PMID- 20794498
TI  - Provincial Medical & Surgical Journal.

PMID- 20794499
TI  - Foreign Department.

PMID- 20794500
TI  - General Retrospect.

PMID- 20794501
TI  - Cases of Faecal Abscess.

PMID- 20794503
TI  - On the Administration of Diuretics in Some Cases of Dropsical Effusion.

PMID- 20794502
TI  - Facts Relative to Epidemic Cholera, Detailed from Personal Observation of the
      Disease, at Plymouth, in 1832.

PMID- 20794504
TI  - Hospital Reports.

PMID- 20794505
TI  - Provincial Medical & Surgical Journal.

PMID- 20794506
TI  - Foreign Department.

PMID- 20794507
TI  - The Dinner, at Bath: Dr. Wood's Speech.

PMID- 20794508
TI  - Case of Fungus Haematodes in the Brain.

PMID- 20794509
TI  - Case of General Anasarca, with Albuminous Urine, in an Infant Ten Weeks Old.

PMID- 20794510
TI  - Observations on Hernia.

PMID- 20794511
TI  - Short Notes on the Opinions and Practice of the Late John Pearson, Esq., F.R.S.,
      on Syphilitic Disease.

PMID- 20794513
TI  - Hospital Reports.

PMID- 20794512
TI  - Cases from Private Practice.

PMID- 20794514
TI  - Provincial Medical & Surgical Journal.

PMID- 20794515
TI  - Inquest on a Case of Alleged Poisoning by Belladonna.

PMID- 20794516
TI  - General Retrospect.

PMID- 20794517
TI  - Memoir on Turning, as an Alternative for Craniotomy and the Long Forceps, in
      Deformity of the Brim of the Pelvis, &c. &c.

PMID- 20794518
TI  - Case of Rheumatic Endocarditis and Chorea, with Observations.

PMID- 20794519
TI  - On the Medical and General Treatment of Local Diseases in Preference to Their
      Treatment by Operation.

PMID- 20794520
TI  - Cases from Private Practice.

PMID- 20794521
TI  - Hospital Reports.

PMID- 20794523
TI  - Foreign Department.

PMID- 20794522
TI  - Provincial Medical & Surgical Journal.

PMID- 20794525
TI  - General Retrospect.

PMID- 20794524
TI  - Notes from a Practitioner's Day Book.

PMID- 20794526
TI  - Retrospective Address: Delivered at the Seventh Anniversary of the Reading
      Pathological Society, June 21st, 1848.

PMID- 20794527
TI  - Cases of Oxaluria.

PMID- 20794528
TI  - Short Notes on the Opinions and Practice of the Late John Pearson, Esq., F.R.S.,
      on Syphilitic Disease.

PMID- 20794529
TI  - On the Efficacy of the Sulphate of Bebeerine in Strumous Ophthalmia.

PMID- 20794530
TI  - Cases from Private Practice.

PMID- 20794531
TI  - Hospital Reports.

PMID- 20794532
TI  - Provincial Medical & Surgical Journal.

PMID- 20794533
TI  - Foreign Department.

PMID- 20794534
TI  - Notes from a Practitioner's Day Book.

PMID- 20794535
TI  - General Retrospect.

PMID- 20794536
TI  - Retrospective Address: Delivered at the Seventh Anniversary of the Reading
      Pathological Society, June 21st, 1848.

PMID- 20794537
TI  - Observations on Cholera.

PMID- 20794538
TI  - Case of Purpura Haemorrhagica.

PMID- 20794540
TI  - Hospital Reports.

PMID- 20794539
TI  - Case of Acute Hydrocephalus: Iodine: Cure.

PMID- 20794542
TI  - General Retrospect.

PMID- 20794541
TI  - Provincial Medical & Surgical Journal.

PMID- 20794543
TI  - Extracts from a Report: On the Sanitary Commission, the Board of Health, and the
      Asiatic Cholera.

PMID- 20794544
TI  - On the Treatment of Rheumatic Paralysis by Electro-Magnetism.

PMID- 20794545
TI  - Cases of Oxaluria.

PMID- 20794547
TI  - Provincial Medical & Surgical Journal.

PMID- 20794546
TI  - Traumatic Fistula of Steno's Duct: Cure Completed during a Continued Fever.

PMID- 20794548
TI  - Foreign Department.

PMID- 20794550
TI  - Notes from a Practitioner's Day Book.

PMID- 20794549
TI  - Royal College of Physicians of London: Directions Relative to the Prevention and
      Treatment of Cholera.

PMID- 20794551
TI  - General Retrospect.

PMID- 20794552
TI  - The Medical Directory.

PMID- 20794553
TI  - Lecture on the Nature & Treatment of Cholera: Considered with Reference to Its
      Analogy with Congestive Agues of Quotidian Type.

PMID- 20794554
TI  - Case of Fungoid Disease of the Pancreas.

PMID- 20794555
TI  - On the Necessity of Employing the Chloroform in a State of Purity.

PMID- 20794556
TI  - Short Notes on the Opinions and Practice of the Late John Pearson, Esq., F.R.S.,
      on Syphilitic Disease.

PMID- 20794557
TI  - Case of Poisoning by Yew Berries.

PMID- 20794558
TI  - Provincial Medical & Surgical Journal.

PMID- 20794559
TI  - General Retrospect.

PMID- 20794560
TI  - Notice of Dr. Twining.

PMID- 20794561
TI  - Notice of Dr. Mayd.

PMID- 20794562
TI  - Lecture on the Nature & Treatment of Cholera: Considered with Reference to Its
      Analogy with Congestive Agues of Quotidian Type.

PMID- 20794564
TI  - Hospital Reports.

PMID- 20794563
TI  - Observations on Cholera.

PMID- 20794565
TI  - Provincial Medical & Surgical Journal.

PMID- 20794566
TI  - Manchester School of Medicine.

PMID- 20794567
TI  - Lecture on the Nature & Treatment of Cholera: Considered with Reference to Its
      Analogy with Congestive Agues of Quotidian Type.

PMID- 20794569
TI  - Provincial Medical & Surgical Journal.

PMID- 20794568
TI  - Bronchitis and Death: In Consequence of Two Teeth Being Driven Down the Larynx.

PMID- 20794570
TI  - Notes from a Practitioner's Day Book.

PMID- 20794571
TI  - Action against a Railway Company for Professional Services: Sands Cox v. the
      Midland Railway Company.

PMID- 20794572
TI  - Hospital Reports.

PMID- 20794573
TI  - Provincial Medical & Surgical Journal.

PMID- 20794574
TI  - Foreign Department.

PMID- 20794575
TI  - General Retrospect.

PMID- 20794576
TI  - Falkner's Liquor Opii Sedativus.

PMID- 20794578
TI  - Case of Intestinal Concretion.

PMID- 20794577
TI  - Case of Acute Laryngitis, with Observations.

PMID- 20794579
TI  - Memoir on Turning: As an Alternative for Craniotomy and the Long Forceps, in
      Deformity of the Brim of the Pelvis, &c. &c.

PMID- 20794580
TI  - A Course of Lectures on Surgery: delivered in the Medical School of Cambridge.

PMID- 20794581
TI  - The Contagion of Asiatic Cholera.

PMID- 20794582
TI  - Short Notes on the Opinions and Practice of the Late John Pearson, Esq., F.R.S.,
      on Syphilitic Disease.

PMID- 20794583
TI  - A Case of Incomplete Reduction "En Masse" of an Inguinal Rupture: With the
      Subsequent Treatment, and Appearances of the Parts Post Mortem.

PMID- 20794584
TI  - Case of Sudden Death, Connected with Pregnancy: Phlebitis and Duodenitis.

PMID- 20794586
TI  - Foreign Department.

PMID- 20794585
TI  - Provincial Medical & Surgical Journal.

PMID- 20794587
TI  - General Retrospect.

PMID- 20794588
TI  - Notice of the Late Dr. James Cowles Prichard, F.R.S.

PMID- 20794589
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794590
TI  - The Contagion of Asiatic Cholera.

PMID- 20794591
TI  - Remarks, Historical and Practical, on Diseases of Infancy.

PMID- 20794592
TI  - Case of Poisoning by Arsenic: Presenting Some Peculiarities.

PMID- 20794594
TI  - Foreign Department.

PMID- 20794593
TI  - Provincial Medical & Surgical Journal.

PMID- 20794595
TI  - Notice of W. Henchman Crowfoot, Esq., F.R.C.S., of Beccles.

PMID- 20794596
TI  - Hospital Reports.

PMID- 20794598
TI  - General Retrospect.

PMID- 20794597
TI  - Provincial Medical & Surgical Journal.

PMID- 20794599
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794601
TI  - Cases from Private Practice.

PMID- 20794600
TI  - The Contagion of Asiatic Cholera.

PMID- 20794602
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794603
TI  - Cases from Private Practice.

PMID- 20794604
TI  - Case of Ulcerated Stomach.

PMID- 20794605
TI  - On Mesmerism.

PMID- 20794606
TI  - Clinical Notes from Private Practice.

PMID- 20794607
TI  - Hospital Reports.

PMID- 20794608
TI  - Provincial Medical & Surgical Journal.

PMID- 20794609
TI  - Convention of Poor Law Medical Officers.

PMID- 20794611
TI  - Notes from a Practitioner's Day Book.

PMID- 20794610
TI  - Notes on America: Its Medical Schools and Establishments.

PMID- 20794612
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794613
TI  - Observations on Scurvy as It Was Developed in Bath and Its Neighbourhood, in the
      Spring of 1847.

PMID- 20794614
TI  - Case of Empyema: In Which Nineteen Pints and a Half of Pus Were Removed by an
      Opening Made into the Cavity of the Chest, with Remarks.

PMID- 20794615
TI  - Clinical Illustrations: On Corroding Ulcer of the Uterus: Case and Remarks.

PMID- 20794616
TI  - Provincial Medical & Surgical Journal.

PMID- 20794617
TI  - Foreign Department.

PMID- 20794618
TI  - General Retrospect.

PMID- 20794619
TI  - The London and Provincial Medical Directory, and Mr. Dawson's Pamphlet.

PMID- 20794620
TI  - Observations on Scurvy as It Was Developed in Bath and Its Neighbourhood, in the
      Spring of 1847.

PMID- 20794621
TI  - Case of Pessary Impacted within the Vagina for Two Years.

PMID- 20794622
TI  - Case of Placenta Praevia.

PMID- 20794623
TI  - Clinical Illustrations: On Corroding Ulcer of the Uterus: Case and Remarks.

PMID- 20794624
TI  - On the Administration of Camphor in Chloroform.

PMID- 20794625
TI  - Provincial Medical & Surgical Journal.

PMID- 20794626
TI  - Foreign Department.

PMID- 20794627
TI  - On Life Insurance among Medical Men: Provident Societies: Annuity & Endowment
      Institutions: And the Benevolent Fund.

PMID- 20794628
TI  - Notes on America: Its Medical Schools and Establishments.

PMID- 20794629
TI  - General Retrospect.

PMID- 20794630
TI  - Medical Legislation: Memorial to the Right Honourable Sir George Grey, Bart.,
      M.P.

PMID- 20794632
TI  - Cod-Liver Oil in Phthisis.

PMID- 20794631
TI  - Local Application of Chloroform in Otalgia and Odontalgia.

PMID- 20794633
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794635
TI  - Observations on Scurvy: As It Was Developed in Bath and Its Neighbourhood, in the
      Spring of 1847.

PMID- 20794634
TI  - Observations on Asiatic Cholera.

PMID- 20794636
TI  - Provincial Medical & Surgical Journal.

PMID- 20794637
TI  - On Life Insurance Among Medical Men: Provident Societies: Annuity & Endowment
      Institutions: And the Benevolent Fund.

PMID- 20794638
TI  - General Retrospect.

PMID- 20794639
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794640
TI  - On the Medical and General Treatment of Local Disease: In Preference to
      Operation.

PMID- 20794641
TI  - Clinical Illustrations: Cancer and Fibrous Tumour of the Uterus: Case and
      Remarks.

PMID- 20794642
TI  - Hospital Reports.

PMID- 20794643
TI  - Provincial Medical & Surgical Journal.

PMID- 20794644
TI  - Foreign Department.

PMID- 20794645
TI  - Medical Legislation.

PMID- 20794646
TI  - General Retrospect.

PMID- 20794647
TI  - On Anteversion of the Uterus.

PMID- 20794648
TI  - Clinical Illustrations: Cancer of the Uterus, Bladder, &c.: Case and Remarks.

PMID- 20794649
TI  - Total Suppression of Urine during Seven Days: Terminating in Recovery.

PMID- 20794650
TI  - On Abscesses of the Pelvis Unconnected with Parturition.

PMID- 20794651
TI  - Hospital Reports.

PMID- 20794652
TI  - Provincial Medical & Surgical Journal.

PMID- 20794653
TI  - Notes on America: Its Medical Schools and Establishments.

PMID- 20794654
TI  - General Retrospect.

PMID- 20794655
TI  - Extraordinary Birth.

PMID- 20794656
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794657
TI  - On the Treatment of Hernia with Opium.

PMID- 20794658
TI  - On the Use of the Extractum Cotyledonis Umbilici in Epilepsy.

PMID- 20794660
TI  - Hospital Reports.

PMID- 20794659
TI  - Remarks, Historical and Practical, on Diseases of Infants.

PMID- 20794661
TI  - Provincial Medical & Surgical Journal.

PMID- 20794662
TI  - General Retrospect.

PMID- 20794663
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794664
TI  - Clinical Notes from Private Practice.

PMID- 20794665
TI  - A Biographical Notice of Robert James Nicholl Streeten, M.D., F.L.S.

PMID- 20794666
TI  - Provincial Medical & Surgical Journal.

PMID- 20794667
TI  - Memorial to Sir George Grey, Bart.

PMID- 20794668
TI  - General Retrospect.

PMID- 20794669
TI  - On Retroversion of the Uterus.

PMID- 20794670
TI  - On the Structure of the Synovial Membrane Covering the Surface of Articular
      Cartilages.

PMID- 20794671
TI  - Case of Infantile Diabetes.

PMID- 20794672
TI  - Cases of Poisoning by the Acetate of Lead, with Remarks.

PMID- 20794673
TI  - Fibrous Tumour of the Uterus, &c.: Case and Remarks.

PMID- 20794674
TI  - Hospital Reports.

PMID- 20794675
TI  - Provincial Medical & Surgical Journal.

PMID- 20794676
TI  - Foreign Department.

PMID- 20794677
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794678
TI  - On Longevity.

PMID- 20794679
TI  - Hospital Reports.

PMID- 20794680
TI  - Provincial Medical & Surgical Journal.

PMID- 20794682
TI  - Foreign Department.

PMID- 20794681
TI  - Dr. Ranking's Inquiries: On Cod-Liver Oil in Phthisis.

PMID- 20794683
TI  - General Retrospect.

PMID- 20794684
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794685
TI  - Case of Abscess in the Spleen: Opening through the Left Lung above the Clavicle.

PMID- 20794686
TI  - Successful Case of Lithotrity.

PMID- 20794687
TI  - Accidental Introduction of a "Puff-Dart" into the Left Bronchus, Followed by
      Abscess: And Its Expulsion during a Fit of Coughing, Enveloped in Pus: Complete
      Recovery.

PMID- 20794688
TI  - Provincial Medical & Surgical Journal.

PMID- 20794689
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794690
TI  - A Successful Case of Caesarean Section: With Remarks.

PMID- 20794692
TI  - Claim to Priority of the Application of Nitrate of Silver in Ulceration of the
      Larynx.

PMID- 20794691
TI  - Compound Dislocation and Removal of the Astragalus.

PMID- 20794693
TI  - Hospital Reports.

PMID- 20794694
TI  - Provincial Medical & Surgical Journal.

PMID- 20794695
TI  - Observations upon the Sale of Arsenic & the Prevention of Secret Poisoning.

PMID- 20794697
TI  - General Retrospect.

PMID- 20794696
TI  - Foreign Department.

PMID- 20794698
TI  - Notice of Dr. Thackeray.

PMID- 20794699
TI  - A Successful Case of Ovariotomy: By the Large Abdominal Section.

PMID- 20794700
TI  - On Latent and Circumscribed Pleurisy: With Effusion.

PMID- 20794701
TI  - Case of Aneurism of the Arch of the Aorta, Simulating Laryngitis.

PMID- 20794702
TI  - Clinical Illustrations: Menorrhagia, Uterine Congestion, &c.

PMID- 20794704
TI  - Hospital Reports.

PMID- 20794703
TI  - Case of Cynanche Tonsillaris: Sudden Death by Asphyxia: Passage of the Purulent
      Matter of an Abscess into the Larynx and Trachea.

PMID- 20794705
TI  - Poisonous Effects of Arsenical Pigments.

PMID- 20794706
TI  - Provincial Medical & Surgical Journal.

PMID- 20794707
TI  - General Retrospect.

PMID- 20794708
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794709
TI  - Cases of Congenital Defects of the Iris.

PMID- 20794710
TI  - Urea Detected in the Rice-Water Evacuations of Cholera.

PMID- 20794711
TI  - Provincial Medical & Surgical Journal.

PMID- 20794712
TI  - Hospital Reports.

PMID- 20794714
TI  - Foreign Department.

PMID- 20794713
TI  - Notes on America: Its Medical Schools and Establishments.

PMID- 20794715
TI  - General Retrospect.

PMID- 20794716
TI  - On Osseous Tumours Growing from the Walls of the Meatus Externus of the Ear: And
      on the Enlargement of the Walls Themselves; With Cases.

PMID- 20794717
TI  - Practical Observations.

PMID- 20794719
TI  - Hospital Reports.

PMID- 20794718
TI  - Clinical Remarks on a Case of Ascites: In Which Paracentesis Was Performed with a
      Successful Result.

PMID- 20794721
TI  - Foreign Department.

PMID- 20794720
TI  - Provincial Medical & Surgical Journal.

PMID- 20794722
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794724
TI  - Hospital Reports.

PMID- 20794723
TI  - On a Peculiar Eruption on the Arms and Hands: Caused by the Irritation of the
      Aphis Infesting the Red Currant.

PMID- 20794725
TI  - Provincial Medical & Surgical Journal.

PMID- 20794726
TI  - Foreign Department.

PMID- 20794727
TI  - General Retrospect.

PMID- 20794728
TI  - Observations upon Injuries of the Head.

PMID- 20794729
TI  - On Certain Physiological and Other Facts: Observed during the Treatment of Spinal
      Disease.

PMID- 20794730
TI  - Hospital Reports.

PMID- 20794731
TI  - Chloroform in Hydrophobia.

PMID- 20794733
TI  - Foreign Department.

PMID- 20794732
TI  - Provincial Medical & Surgical Journal.

PMID- 20794734
TI  - General Retrospect.

PMID- 20794735
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794736
TI  - On Ovariotomy.

PMID- 20794737
TI  - Hospital Reports.

PMID- 20794738
TI  - Provincial Medical & Surgical Journal.

PMID- 20794740
TI  - Foreign Department.

PMID- 20794739
TI  - Inquiry on Cholera.

PMID- 20794741
TI  - General Retrospect.

PMID- 20794742
TI  - Observations upon Injuries of the Head.

PMID- 20794743
TI  - Remarks, Historical and Practical: On Diseases of Infants.

PMID- 20794744
TI  - Hospital Reports.

PMID- 20794745
TI  - Provincial Medical & Surgical Journal.

PMID- 20794747
TI  - General Retrospect.

PMID- 20794746
TI  - Foreign Department.

PMID- 20794748
TI  - Alleged Death from the Inhalation of Chloroform.

PMID- 20794749
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794750
TI  - Case of Long Retained Pessary.

PMID- 20794751
TI  - Hospital Reports.

PMID- 20794752
TI  - Provincial Medical & Surgical Journal.

PMID- 20794753
TI  - Inquiry on Cholera: Proposed Plan of Procedure-First Fruits.

PMID- 20794754
TI  - Foreign Department.

PMID- 20794756
TI  - Provincial Medical & Surgical Journal.

PMID- 20794755
TI  - General Retrospect.

PMID- 20794757
TI  - Foreign Department.

PMID- 20794759
TI  - Case of Malformation.

PMID- 20794758
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794760
TI  - Provincial Medical & Surgical Journal.

PMID- 20794761
TI  - Inquiry on Cholera: No. II.

PMID- 20794762
TI  - Foreign Department.

PMID- 20794763
TI  - General Retrospect.

PMID- 20794764
TI  - Illustrations of the Tolerance of Injuries Occasionally Exhibited by the Brain.

PMID- 20794765
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794766
TI  - Statistics of Blindness.

PMID- 20794767
TI  - Hospital Reports.

PMID- 20794768
TI  - Provincial Medical & Surgical Journal.

PMID- 20794769
TI  - Foreign Department.

PMID- 20794770
TI  - General Retrospect.

PMID- 20794771
TI  - Case of Morbus Coxarius of Six Years' Standing: In Which Excision of the Head of
      the Femur Was Successfully Performed.

PMID- 20794772
TI  - An Account of an Epidemic of Typhoid Fever, Which Prevailed in Bath: During the
      Months of September and October, 1849.

PMID- 20794774
TI  - Hospital Reports.

PMID- 20794773
TI  - Case of Unexpected Recovery from a Severe Pulmonary Affection: Simulating
      Tubercular Phthisis.

PMID- 20794775
TI  - Provincial Medical & Surgical Journal.

PMID- 20794776
TI  - Inquiry on Cholera: No. III.

PMID- 20794777
TI  - Foreign Department.

PMID- 20794778
TI  - General Retrospect.

PMID- 20794780
TI  - General Retrospect.

PMID- 20794779
TI  - Foreign Department.

PMID- 20794781
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794783
TI  - On the Primary Introduction of the Oleum Jecoris Aselli or Cod-Liver Oil as an
      Internal Remedy for Disease.

PMID- 20794782
TI  - Case of Hereditary Cataract.

PMID- 20794785
TI  - Provincial Medical & Surgical Journal.

PMID- 20794784
TI  - Hospital Reports.

PMID- 20794786
TI  - Inquiry on Cholera: No. IV.

PMID- 20794787
TI  - Remarks on Epilepsy or Puerperal Convulsions.

PMID- 20794788
TI  - Case of Puerperal Convulsions with Puerperal Mania: Terminating Successfully.

PMID- 20794790
TI  - Hospital Reports.

PMID- 20794789
TI  - Observations on a Case of Apoplexy: In Which Death Apparently Commenced at the
      Heart.

PMID- 20794792
TI  - Foreign Department.

PMID- 20794791
TI  - Provincial Medical & Surgical Journal.

PMID- 20794793
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794795
TI  - Provincial Medical & Surgical Journal.

PMID- 20794794
TI  - Brief Notes of Medical Cases: Selected from Hospital and Private Practice.

PMID- 20794796
TI  - Inquiry on Cholera: No. V.

PMID- 20794797
TI  - General Retrospect.

PMID- 20794798
TI  - Vaccination: Its Origin and Efficacy, and the Necessity of Further Legislative
      Enactments to Extend Its Protective Powers.

PMID- 20794799
TI  - Hospital Reports.

PMID- 20794800
TI  - Provincial Medical & Surgical Journal.

PMID- 20794802
TI  - Report on Cod-Liver Oil.

PMID- 20794801
TI  - Memorial to Sir George Grey, Bart.

PMID- 20794803
TI  - Foreign Department.

PMID- 20794804
TI  - General Retrospect.

PMID- 20794805
TI  - Report of the Deputation to Sir George Grey.

PMID- 20794807
TI  - Cases of Craniotomy, with Remarks.

PMID- 20794806
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794808
TI  - Provincial Medical & Surgical Journal.

PMID- 20794809
TI  - Inquiry on Cholera: No. VI.

PMID- 20794810
TI  - General Retrospect.

PMID- 20794812
TI  - Provincial Medical & Surgical Journal.

PMID- 20794811
TI  - Cases of Malignant Diseases of the Eye, with Observations.

PMID- 20794813
TI  - Foreign Department.

PMID- 20794814
TI  - Case of Long Standing Disease of the Lungs Simulating Phthisis: Death by
      Inanition from a Pouch at the Lower End of the OEsophagus.

PMID- 20794816
TI  - Hospital Reports.

PMID- 20794815
TI  - Brief Notes of Medical Cases: Selected from Hospital and Private Practice.

PMID- 20794817
TI  - Provincial Medical & Surgical Journal.

PMID- 20794818
TI  - Notice to Members.

PMID- 20794819
TI  - Inquiry on Cholera: No. VII.

PMID- 20794821
TI  - Brief Notes of Medical Cases: Selected from Hospital and Private Practice.

PMID- 20794820
TI  - Memorial of the President and Council of the Provincial Medical and Surgical
      Association.

PMID- 20794822
TI  - Case of Compound Fracture of the Right Leg: With Severe Laceration, Secondary
      Amputation, and Death.

PMID- 20794823
TI  - Provincial Medical & Surgical Journal.

PMID- 20794824
TI  - Case of Supposed Spina Bifida Spontaneously Cured.

PMID- 20794826
TI  - General Retrospect.

PMID- 20794825
TI  - Foreign Department.

PMID- 20794828
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794827
TI  - Gloucestershire Medical and Surgical Association.

PMID- 20794829
TI  - Case of Cataleptiform Hysteria: Apparently Induced by Mesmerism, with Remarks.

PMID- 20794831
TI  - Observations: Suggested by Mr. Newnham's "Cursory Remarks on Vaccination".

PMID- 20794830
TI  - Cases of Craniotomy.

PMID- 20794832
TI  - Hospital Reports.

PMID- 20794833
TI  - Provincial Medical & Surgical Journal.

PMID- 20794834
TI  - General Retrospect.

PMID- 20794835
TI  - Foreign Department.

PMID- 20794836
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794837
TI  - Case of Uterine Polypus Coexisting with Pregnancy and Spontaneous Expulsion of
      the Tumour.

PMID- 20794838
TI  - On Traumatic Tetanus.

PMID- 20794839
TI  - Provincial Medical & Surgical Journal.

PMID- 20794840
TI  - Supposed Death from Lobelia Inflata.

PMID- 20794841
TI  - Practical Observations on the Vaccination Question.

PMID- 20794842
TI  - Cases of Poisoning.

PMID- 20794843
TI  - Case of Gangrene of the Lung.

PMID- 20794844
TI  - Hospital Reports.

PMID- 20794845
TI  - Provincial Medical & Surgical Journal.

PMID- 20794846
TI  - Foreign Department.

PMID- 20794847
TI  - General Retrospect.

PMID- 20794848
TI  - Observations and Inquiries Concerning Hydatids of the Liver.

PMID- 20794849
TI  - On Rheumatic Affections of the Ear.

PMID- 20794850
TI  - Malignant Disease of the Eye-Ball: Extirpation and Recovery.

PMID- 20794851
TI  - Case of Necrosis of the Inferior Maxillary Bone: As an Effect of Mercurial
      Salivation.

PMID- 20794852
TI  - Hospital Reports.

PMID- 20794853
TI  - Provincial Medical & Surgical Journal.

PMID- 20794855
TI  - General Retrospect.

PMID- 20794854
TI  - Foreign Department.

PMID- 20794856
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794858
TI  - On Puerperal Fever.

PMID- 20794857
TI  - On the Use of Cold Water as a Powerful Remedial Agent in Chronic Disease.

PMID- 20794859
TI  - On the Structure of the Membrana Tympani in the Human Ear.

PMID- 20794860
TI  - Thoughts on Passing Events.

PMID- 20794861
TI  - Hospital Reports.

PMID- 20794862
TI  - Provincial Medical & Surgical Journal.

PMID- 20794863
TI  - Inquiry on Cholera: No. VIII.

PMID- 20794864
TI  - Foreign Department.

PMID- 20794865
TI  - Remarks on Oozing Tumour of the Labium, with a Case.

PMID- 20794866
TI  - Remarks on a Case of Punctured Wound of the Neck of a New-Born Child: Supposed to
      Have Been Inflicted with an Awl.

PMID- 20794867
TI  - Case of Obstructed Vagina: With Remarks.

PMID- 20794868
TI  - Provincial Medical & Surgical Journal.

PMID- 20794870
TI  - Foreign Department.

PMID- 20794869
TI  - Imperforate Anus Treated by Amussat's Operation.

PMID- 20794871
TI  - General Retrospect.

PMID- 20794872
TI  - Report on Cholera.

PMID- 20794873
TI  - On the Protective Power of Vaccination.

PMID- 20794875
TI  - Hospital Reports.

PMID- 20794874
TI  - Case of Oblique Strangulated Hernia, with Remarks.

PMID- 20794876
TI  - Provincial Medical & Surgical Journal.

PMID- 20794877
TI  - Foreign Department.

PMID- 20794878
TI  - General Retrospect.

PMID- 20794879
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794880
TI  - Case of Malformed and Imperforate Vagina.

PMID- 20794881
TI  - Cases in Private Practice.

PMID- 20794882
TI  - Cases of Nervous Disorders Treated by Mesmerism.

PMID- 20794884
TI  - Hospital Reports.

PMID- 20794883
TI  - Thoughts on Passing Events.

PMID- 20794885
TI  - Provincial Medical & Surgical Journal.

PMID- 20794886
TI  - Foreign Department.

PMID- 20794887
TI  - General Retrospect.

PMID- 20794888
TI  - On Rheumatic Affections of the Ear.

PMID- 20794889
TI  - Case of Dislocation of the Scaphoid Bone of the Foot.

PMID- 20794890
TI  - On a New Swinging Apparatus for the Treatment of Fracture of the Leg.

PMID- 20794892
TI  - Hospital Reports.

PMID- 20794891
TI  - Case of Ununited Fracture.

PMID- 20794893
TI  - Provincial Medical & Surgical Journal.

PMID- 20794894
TI  - Foreign Department.

PMID- 20794895
TI  - General Retrospect.

PMID- 20794896
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794897
TI  - On the Present State of Therapeutics.

PMID- 20794899
TI  - Case of Polypus Uteri, with Retroflexion.

PMID- 20794898
TI  - Successful Case of Ovariotomy.

PMID- 20794901
TI  - Provincial Medical & Surgical Journal.

PMID- 20794900
TI  - Hospital Reports.

PMID- 20794902
TI  - Biographical Notice of the Late John Green Crosse, Esq., F.R.S.

PMID- 20794903
TI  - Foreign Department.

PMID- 20794904
TI  - General Retrospect.

PMID- 20794905
TI  - An Inaugural Address: Delivered at the Opening of the Chatham Street School of
      Medicine, Manchester, October 1st, 1850.

PMID- 20794906
TI  - Case of Diseased Heart.

PMID- 20794907
TI  - Rheumatism of the Diaphragm.

PMID- 20794909
TI  - Hospital Reports.

PMID- 20794908
TI  - Case in Which a Silk Handkerchief Was Swallowed by a Boy Aged Nine Years.

PMID- 20794911
TI  - Foreign Department.

PMID- 20794910
TI  - Provincial Medical & Surgical Journal.

PMID- 20794913
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794912
TI  - General Retrospect.

PMID- 20794914
TI  - Cases of Rheumatic Fever.

PMID- 20794915
TI  - Observations on Hydatid Disease of the Liver.

PMID- 20794916
TI  - Case of Sudden Death Seven Hours after Delivery-Air Found in the Heart.

PMID- 20794917
TI  - Remarks on the Use of Cod-Liver Oil in Jail Cachexia.

PMID- 20794918
TI  - Hospital Reports.

PMID- 20794919
TI  - Provincial Medical & Surgical Journal.

PMID- 20794921
TI  - General Retrospect.

PMID- 20794920
TI  - Foreign Department.

PMID- 20794923
TI  - Testimonial to Mr. J. F. Clarke.

PMID- 20794922
TI  - Biographical Notice of the Late Thos. Dorrington, Esq.

PMID- 20794924
TI  - A Case of Adhesion of the Labia: By Which the Birth of a Child Was Impeded for an
      Hour; Division of the Parts Followed by Immediate Expulsion of the Infant.

PMID- 20794925
TI  - Practical Observations on Delirium.

PMID- 20794926
TI  - On the Differential Diagnosis of Functional and Organic Diseases of the Heart in
      Anaemic Subjects.

PMID- 20794927
TI  - Provincial Medical & Surgical Journal.

PMID- 20794928
TI  - Foreign Department.

PMID- 20794929
TI  - General Retrospect.

PMID- 20794930
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794932
TI  - Provincial Medical & Surgical Journal.

PMID- 20794931
TI  - Hospital Reports.

PMID- 20794933
TI  - Foreign Department.

PMID- 20794934
TI  - On Disintegration of the Blood.

PMID- 20794935
TI  - Cases of Fever, with Remarks.

PMID- 20794937
TI  - Provincial Medical & Surgical Journal.

PMID- 20794936
TI  - Hospital Reports.

PMID- 20794938
TI  - General Retrospect.

PMID- 20794939
TI  - A Bill: For the Incorporation of General Practitioners in Medicine, Surgery, and
      Midwifery.

PMID- 20794940
TI  - Case of Ovariotomy.

PMID- 20794941
TI  - On the Comparative Size of the Hand of the Accoucheur and of the Female Pelvis.

PMID- 20794942
TI  - Remarks upon a Case in Which There Were Evidences of Dilated Bronchi: And Which
      Was Complicated by Occasional Expectoration of Thin, Fibrinous, Cup-Shaped, False
      Membranes.

PMID- 20794943
TI  - Cases of Ovarian Dropsy.

PMID- 20794945
TI  - Provincial Medical & Surgical Journal.

PMID- 20794944
TI  - Three Cases of Ovarian Disease: One Operated on-Fatal.

PMID- 20794947
TI  - General Retrospect.

PMID- 20794946
TI  - Foreign Department.

PMID- 20794948
TI  - A Bill: For the Incorporation of General Practitioners in Medicine, Surgery, and
      Midwifery.

PMID- 20794949
TI  - Observations on Hydatid Disease of the Liver.

PMID- 20794950
TI  - Death Caused by the Inhalation of Chloroform.

PMID- 20794952
TI  - Hospital Reports.

PMID- 20794951
TI  - Remarks on Cases in Private Practice.

PMID- 20794954
TI  - Foreign Department.

PMID- 20794953
TI  - Provincial Medical & Surgical Journal.

PMID- 20794956
TI  - Death of Dr. Haviland.

PMID- 20794955
TI  - General Retrospect.

PMID- 20794957
TI  - Foreign Department.

PMID- 20794958
TI  - General Retrospect.

PMID- 20794959
TI  - Convention of Poor Law Medical Officers.

PMID- 20794960
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794961
TI  - On the Exaggeration of Ideas Relative to Certain Sanitary Topics.

PMID- 20794963
TI  - Provincial Medical & Surgical Journal.

PMID- 20794962
TI  - On Gouty Affections of the Ear.

PMID- 20794964
TI  - Cases of Hydatid Disease, with Observations.

PMID- 20794966
TI  - Cases of Chorea: Treated Successfully with Carbonate of Iron.

PMID- 20794965
TI  - Manslaughter from a Blow on the Head with the Fist, Causing Fracture of the Inner
      Table of the Skull.

PMID- 20794967
TI  - Hospital Reports.

PMID- 20794968
TI  - Provincial Medical & Surgical Journal.

PMID- 20794970
TI  - General Retrospect.

PMID- 20794969
TI  - Foreign Department.

PMID- 20794971
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20794973
TI  - Provincial Medical & Surgical Journal.

PMID- 20794972
TI  - On the Right Management of Young Women: Before the First Appearance of
      Menstruation.

PMID- 20794974
TI  - Foreign Department.

PMID- 20794975
TI  - General Retrospect.

PMID- 20794976
TI  - University of Cambridge: Natural Sciences Tripos. Cambridge, March 8th, 1851.

PMID- 20794978
TI  - Observations on the Sale of Arsenic Regulation Bill.

PMID- 20794977
TI  - Remarks on the Caesarean Section, Craniotomy, and on the Induction of Premature
      Labour.

PMID- 20794979
TI  - Provincial Medical & Surgical Journal.

PMID- 20794980
TI  - Foreign Department.

PMID- 20794982
TI  - University of Cambridge: Natural Sciences Tripos Cambridge, March 8th, 1851.

PMID- 20794981
TI  - General Retrospect.

PMID- 20794983
TI  - Of the Causes, Diagnosis, and Treatment of Obstructions of the Intestines.

PMID- 20794984
TI  - Cases of Affections of the Nerves: Distributed to the Eye and Its Appendages.

PMID- 20794985
TI  - On the Right Management of Women: At First Menstruation, and during the
      Persistence of That Function.

PMID- 20794987
TI  - Foreign Department.

PMID- 20794986
TI  - Provincial Medical & Surgical Journal.

PMID- 20794988
TI  - General Retrospect.

PMID- 20794989
TI  - The Apothecaries' Company v. Thomas Fawthrop of Halifax.

PMID- 20794990
TI  - Dysmenorrhoea: And Its Treatment by Dilatation of, and the Application of Caustic
      to, the Uterine Neck.

PMID- 20794992
TI  - Hospital Reports.

PMID- 20794991
TI  - Sexagenarian Thoughts on the Present State of the Medical Profession.

PMID- 20794994
TI  - Foreign Department.

PMID- 20794993
TI  - Provincial Medical & Surgical Journal.

PMID- 20794995
TI  - General Retrospect.

PMID- 20794996
TI  - Introductory Lecture on the Diseases of Children: Delivered in the Chatham Street
      School of Medicine, Manchester, January 14, 1851.

PMID- 20794997
TI  - Observations on the Caesarean Section.

PMID- 20794998
TI  - Novel Operation for Effecting Re-Union of Ununited Tendo-Achillis.

PMID- 20794999
TI  - Sexagenarian Thoughts on the Present State of the Medical Profession.

PMID- 20795000
TI  - Hospital Reports.

PMID- 20795001
TI  - Provincial Medical & Surgical Journal.

PMID- 20795002
TI  - Foreign Department.

PMID- 20795003
TI  - General Retrospect.

PMID- 20795004
TI  - On the Management of Women at, and after the Cessation of, Menstruation.

PMID- 20795005
TI  - Cases in Midwifery.

PMID- 20795006
TI  - On Gouty Inflammation Attacking the Structures of the Ear.

PMID- 20795007
TI  - On the Treatment of the Various Forms of Hernia: By Newson's Patent Wire Truss.

PMID- 20795009
TI  - Provincial Medical & Surgical Journal.

PMID- 20795008
TI  - On the African Fever.

PMID- 20795010
TI  - Foreign Department.

PMID- 20795011
TI  - General Retrospect.

PMID- 20795012
TI  - Clinical Lectures on the Practice of Physic: Delivered in the Theatre of Queen's
      College, Birmingiiam.

PMID- 20795013
TI  - Lecture on the Diseases of Children: Delivered in Tux Chatham Street School of
      Medicine, Manchester.

PMID- 20795014
TI  - Cases in Midwifery.

PMID- 20795015
TI  - On Acetate of Lead.

PMID- 20795016
TI  - Hospital Reports.

PMID- 20795017
TI  - Provincial Medical & Surgical Journal.

PMID- 20795018
TI  - Foreign Department.

PMID- 20795019
TI  - General Retrospect.

PMID- 20795021
TI  - Case of Poisoning by Oxalic Acid.

PMID- 20795020
TI  - On the Management of Women at, and after the Cessation of, Menstruation.

PMID- 20795023
TI  - On the Acetate of Lead.

PMID- 20795022
TI  - Case of Tubal Foetation.

PMID- 20795025
TI  - Provincial Medical & Surgical Journal.

PMID- 20795024
TI  - Hospital Reports.

PMID- 20795026
TI  - Foreign Department.

PMID- 20795027
TI  - General Retrospect.

PMID- 20795028
TI  - Lecture on the Diseases of Children: Delivered in the Chatham Street School of
      Medicine, Manchester.

PMID- 20795030
TI  - Hospital Reports.

PMID- 20795029
TI  - Case of Popliteal Aneurism: Cured by Pressure on the Femoral Artery.

PMID- 20795031
TI  - Provincial Medical & Surgical Journal.

PMID- 20795032
TI  - Foreign Department.

PMID- 20795033
TI  - General Retrospect.

PMID- 20795034
TI  - Charter of the Royal College of Surgeons.

PMID- 20795035
TI  - Orthodox Medicine; An Address: Delivered at the Annual Meeting of the Bath and
      Bristol Branch of the Provincial Medical and Surgical Association.

PMID- 20795037
TI  - Case of a Rare Variety of Spina Bifida.

PMID- 20795036
TI  - Successful Case of Operation for the Removal of an Ovarian Tumour: Weighing
      Twenty-Five Pounds.

PMID- 20795038
TI  - On the Management of Women at, and after the Cessation of, Menstruation.

PMID- 20795039
TI  - Provincial Medical & Surgical Journal.

PMID- 20795040
TI  - Foreign Department.

PMID- 20795041
TI  - General Retrospect.

PMID- 20795042
TI  - Lecture on the Diseases of Children: Delivered in the Chatham Street School of
      Medicine, Manchester.

PMID- 20795043
TI  - Cases in Midwifery.

PMID- 20795044
TI  - Two Cases of Insanity: Illustrative of the Uncertainty of Diagnosis Based on
      Phrenological Indications.

PMID- 20795045
TI  - Case of Stricture of the Urethra.

PMID- 20795046
TI  - Case of Fungus Haematodes of the Bladder.

PMID- 20795047
TI  - Hospital Reports.

PMID- 20795048
TI  - Provincial Medical & Surgical Journal.

PMID- 20795049
TI  - Foreign Department.

PMID- 20795050
TI  - General Retrospect.

PMID- 20795052
TI  - Lecture on the Diseases of Children: Delivered in the Chatham Street School of
      Medicine, Manchester.

PMID- 20795051
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20795053
TI  - Cases in Midwifery: With Remarks.

PMID- 20795054
TI  - Cases in Midwifery.

PMID- 20795055
TI  - Cases in Private Practice.

PMID- 20795056
TI  - A Case of Non-Union of Fracture of Both Bones of the Leg, of Eighteen Weeks'
      Standing, Successfully Treated by Mercury.

PMID- 20795057
TI  - Dr. Thomson's Invalid Lifter.

PMID- 20795059
TI  - Provincial Medical & Surgical Journal.

PMID- 20795058
TI  - Hospital Reports.

PMID- 20795060
TI  - Foreign Department.

PMID- 20795062
TI  - On the Progress of Public Hygiene and Sanitary Legislation in England: And the
      Advantages to Be Derived from Their Further Extension.

PMID- 20795061
TI  - General Retrospect.

PMID- 20795064
TI  - Provincial Medical & Surgical Journal.

PMID- 20795063
TI  - On Uterine Haemorrhage.

PMID- 20795065
TI  - Foreign Department.

PMID- 20795066
TI  - General Retrospect.

PMID- 20795067
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20795068
TI  - On the Progress of Public Hygiene and Sanitary Legislation in England: And the
      Advantages to Be Derived from Their Further Extension.

PMID- 20795069
TI  - Case of Idiopathic Gangrene of the Foot.

PMID- 20795070
TI  - On the Management of Women at, and after the Cessation of, Menstruation.

PMID- 20795072
TI  - Provincial Medical & Surgical Journal.

PMID- 20795071
TI  - Hospital Reports.

PMID- 20795073
TI  - Foreign Department.

PMID- 20795074
TI  - General Retrospect.

PMID- 20795076
TI  - On the Progress of Public Hygiene and Sanitary Legislation in England: And the
      Advantages to Be Derived from Their Further Extension.

PMID- 20795075
TI  - On Arthritic Headache.

PMID- 20795077
TI  - The Left Arm and Hand of a Child Found in a State of Putrescence, from
      Strangulation, the Funis Being Tightly Bound Round It at the Upper Part.

PMID- 20795078
TI  - On the Inefficacy of Kousso in Some Cases of Taenia.

PMID- 20795079
TI  - Provincial Medical & Surgical Journal.

PMID- 20795080
TI  - Foreign Department.

PMID- 20795081
TI  - General Retrospect.

PMID- 20795082
TI  - Notice of the Late Jonah Wilson, Esq., of Huntingdon.

PMID- 20795084
TI  - Case of Popliteal Aneurism: Cured by Pressure upon the Femoral Artery.

PMID- 20795083
TI  - Lecture on the Diseases of Children: Delivered in the Chatham Street School of
      Medicine, Manchester.

PMID- 20795086
TI  - Case of Rupture of the Fallopian Tube.

PMID- 20795085
TI  - Case of Rupture of the Bladder from External Pressure.

PMID- 20795087
TI  - Observations on Nitrate of Silver Stains of the Conjunctiva: Case of Absolute
      Blackness.

PMID- 20795088
TI  - On Medical Delusions & Charlatanic Practices.

PMID- 20795089
TI  - On the Progress of Public Hygiene and Sanitary Legislation in England: And the
      Advantages to Be Derived from Their Further Extension.

PMID- 20795090
TI  - Hospital Reports.

PMID- 20795092
TI  - Foreign Department.

PMID- 20795091
TI  - Provincial Medical & Surgical Journal.

PMID- 20795093
TI  - General Retrospect.

PMID- 20795094
TI  - A Course of Lectures on Surgery: Delivered in the Medical School of Cambridge.

PMID- 20795095
TI  - Abscesses in the Right Lobe of the Cerebellum: With Caries of the Petrous Bone.

PMID- 20795096
TI  - Case of Epidemic Mumps: Complicated with Parotitis, Orchitis, Nephritis,
      Albuminuria, Convulsions: Recovery.

PMID- 20795097
TI  - On the Treatment of Habitual or Chronic Constipation.

PMID- 20795099
TI  - Provincial Medical & Surgical Journal.

PMID- 20795098
TI  - What Our Association Might Do.

PMID- 20795101
TI  - General Retrospect.

PMID- 20795100
TI  - Foreign Department.

PMID- 20795102
TI  - Observations on Hydatid Disease of the Liver.

PMID- 20795103
TI  - What Our Association Might Do.

PMID- 20795104
TI  - Hospital Reports.

PMID- 20795106
TI  - Foreign Department.

PMID- 20795105
TI  - Provincial Medical & Surgical Journal.

PMID- 20795108
TI  - Homoeopathy at Totness: Inquest.

PMID- 20795107
TI  - General Retrospect.

PMID- 20795109
TI  - Lecture on the Diseases of Children: Delivered in the Chatham Street School of
      Medicine, Manchester.

PMID- 20795111
TI  - Some Remarks on Constipation as Attendant on Chronic Uterine Disorders.

PMID- 20795110
TI  - On the Importance of Discriminating between Pregnancy & Abdominal Disease:
      Illustrated by a Very Recent Case.

PMID- 20795112
TI  - On the Treatment of Arthritic Headache.

PMID- 20795114
TI  - Provincial Medical & Surgical Journal.

PMID- 20795113
TI  - What Our Association Might Do.

PMID- 20795115
TI  - General Retrospect.

PMID- 20795116
TI  - Notes on the Treatment of Curable Diseases.

PMID- 20795117
TI  - On the Absence of Phosphates in the Urine of the Herbivora.

PMID- 20795119
TI  - Case of Poisoning by the Bi-Chromate of Potash.

PMID- 20795118
TI  - Cases of Poisoning by Datura Stramonium.

PMID- 20795120
TI  - Strongylus Suis in the Bronchial Tubes of a Pig.

PMID- 20795121
TI  - What Our Association Might Do.

PMID- 20795122
TI  - Provincial Medical & Surgical Journal.

PMID- 20795124
TI  - Hospital Reports.

PMID- 20795123
TI  - Foreign Department.

PMID- 20795125
TI  - Provincial Medical & Surgical Journal.

PMID- 20795126
TI  - Foreign Department.

PMID- 20795127
TI  - General Retrospect.

PMID- 20795128
TI  - On Epilepsy: A Paper read before the Midland Branch of the Provincial Medical and
      Surgical Association, at Derby, December 4th, 1851.

PMID- 20795129
TI  - A Case of Poisoning with Arsenic Acid.

PMID- 20795130
TI  - Notes on the Treatment of Curable Diseases.

PMID- 20795131
TI  - On Prolapsus Uteri: With a Description of a New Instrument for Its Treatment.

PMID- 20795133
TI  - Hospital Reports.

PMID- 20795132
TI  - Fracture of the Humerus at Its Lower-Third.

PMID- 20795134
TI  - Provincial Medical & Surgical Journal.

PMID- 20795135
TI  - Draft Bill: To produce Uniformity of Medical Education and Qualification, and for
      the Registration of those Licensed to Practise in Medicine.

PMID- 20795136
TI  - Foreign Department.

PMID- 20795137
TI  - General Retrospect.

PMID- 20795138
TI  - Some Remarks upon the Identity of Warty Ulceration of Cicatrix with Epithelial
      Cancer, Illustrated by Cases.

PMID- 20795139
TI  - Case of Retention of Bile and Distended Gall-Bladder.

PMID- 20795140
TI  - Observations on Hydatid Disease of the Liver.

PMID- 20795141
TI  - Hospital Reports.

PMID- 20795143
TI  - Foreign Department.

PMID- 20795142
TI  - Provincial Medical & Surgical Journal.

PMID- 20795145
TI  - General Retrospect.

PMID- 20795144
TI  - General Retrospect.

PMID- 20795146
TI  - Case of Aneurism of the Thoracic Aorta: Bursting into the Trachea, Simulating
      Chronic Laryngitis.

PMID- 20795147
TI  - On the Varieties of Cranial Presentation.

PMID- 20795148
TI  - Hospital Reports.

PMID- 20795149
TI  - Provincial Medical & Surgical Journal.

PMID- 20795150
TI  - Lecture on the Diseases of Children: Delivered in the Chatham Street School of
      Medicine, Manchester.

PMID- 20795152
TI  - Hospital Reports.

PMID- 20795151
TI  - Case of Fracture of the Spinous Processes of the Lumbar Vertebrae: Remarks on the
      Treatment of Sprained Back by "Firing".

PMID- 20795154
TI  - Foreign Department.

PMID- 20795153
TI  - Provincial Medical & Surgical Journal.

PMID- 20795155
TI  - General Retrospect.

PMID- 20795157
TI  - Notes on the Treatment of Curable Diseases.

PMID- 20795156
TI  - Case of Ileus with Long-Continued Obstruction.

PMID- 20795159
TI  - Provincial Medical & Surgical Journal.

PMID- 20795158
TI  - Hospital Reports.

PMID- 20795160
TI  - Foreign Department.

PMID- 20795161
TI  - General Retrospect.

PMID- 20795162
TI  - On Uterine Haemorrhage.

PMID- 20795163
TI  - Hospital Reports.

PMID- 20795164
TI  - Provincial Medical & Surgical Journal.

PMID- 20795165
TI  - General Retrospect.

PMID- 20795166
TI  - Lecture on the Diseases of Children: Delivered in the Chatham Street School of
      Medicine, Manchester.

PMID- 20795167
TI  - Case of Strangulation of Three Feet of the Jejunum: By a Rent in the Mesentery,
      Presenting no Symptoms of the Disease for Several Hours, and Then Terminating
      Very Rapidly.

PMID- 20795168
TI  - Hospital Reports.

PMID- 20795169
TI  - Provincial Medical & Surgical Journal.

PMID- 20795170
TI  - Foreign Department.

PMID- 20795171
TI  - Cases of Difficult Parturition.

PMID- 20795172
TI  - Effects of Iodine on the Mammae.

PMID- 20795173
TI  - Hospital Reports.

PMID- 20795174
TI  - Provincial Medical & Surgical Journal.

PMID- 20795175
TI  - Foreign Department.

PMID- 20795176
TI  - General Retrospect.

PMID- 20795177
TI  - Hospital Reports.

PMID- 20795178
TI  - Provincial Medical & Surgical Journal.

PMID- 20795180
TI  - Foreign Department.

PMID- 20795179
TI  - Draft Bill: To produce Uniformity of Medical Education and Qualification, and for
      the Registration of those Licensed to Practise in Medicine.

PMID- 20795181
TI  - General Retrospect.

PMID- 20795182
TI  - Lecture on the Diseases of Children: Delivered in the Chatham Street School of
      Medicine, Manchester.

PMID- 20795183
TI  - Case of Large Single Ovarian Cyst: Treated Successfully by Operation.

PMID- 20795185
TI  - The Life of the Blood, as Viewed in the Light of Popular Belief: From Notes of an
      Introductory Lecture Delivered by the Professor of General Pathology in the
      Faculty of Medicine of Montpellier.

PMID- 20795184
TI  - Remarks on Some Points Connected with Lithotomy.

PMID- 20795186
TI  - Hospital Reports.

PMID- 20795187
TI  - Provincial Medical & Surgical Journal.

PMID- 20795188
TI  - Foreign Department.

PMID- 20795189
TI  - General Retrospect.

PMID- 20795190
TI  - Lecture on the Diseases of Children: Delivered in the Chatham Street School of
      Medicine, Manchester.

PMID- 20795192
TI  - Provincial Medical & Surgical Journal.

PMID- 20795191
TI  - Notes on the Treatment of Curable Diseases.

PMID- 20795193
TI  - Foreign Department.

PMID- 20795194
TI  - General Retrospect.

PMID- 20795195
TI  - On the Diagnosis of Chronic Ovarian Tumours.

PMID- 20795196
TI  - Remarks on the Treatment of Burns and Scalds.

PMID- 20795197
TI  - Case of Loose Cartilages in the Knee-Joint.

PMID- 20795198
TI  - The Life of the Blood, as Viewed in the Light of Popular Belief: From Notes of an
      Introductory Lecture Delivered by the Professor of General Pathology in the
      Faculty of Medicine of Montpellier.

PMID- 20795199
TI  - Provincial Medical & Surgical Journal.

PMID- 20795200
TI  - Foreign Department.

PMID- 20795201
TI  - Notes on the Treatment of Curable Diseases.

PMID- 20795202
TI  - Remarks on the Treatment of Burns and Scalds.

PMID- 20795203
TI  - Two Cases of Vitiligoidea.

PMID- 20795205
TI  - Hospital Reports.

PMID- 20795204
TI  - Case of Wound of Heart by a Needle.

PMID- 20795206
TI  - Provincial Medical & Surgical Journal.

PMID- 20795207
TI  - On a Variety of Latent Pneumonia.

PMID- 20795208
TI  - On the Treatment of Erysipelas by the Muriated Tincture of Iron.

PMID- 20795209
TI  - Case of Puerperal Convulsions.

PMID- 20795210
TI  - Case of Hay Fever.

PMID- 20795211
TI  - Hospital Reports.

PMID- 20795212
TI  - Provincial Medical & Surgical Journal.

PMID- 20795213
TI  - Foreign Department.

PMID- 20795214
TI  - General Retrospect.

PMID- 20795215
TI  - Provincial Medical & Surgical Journal.

PMID- 20795216
TI  - Lectures on the Diseases of Children: Delivered in the Chatham Street School of
      Medicine, Manchester.

PMID- 20795217
TI  - On the Diagnosis of Chronic Ovarian Tumours.

PMID- 20795218
TI  - Case of Inversio Uteri.

PMID- 20795219
TI  - Cases in Private Practice.

PMID- 20795220
TI  - Hospital Reports.

PMID- 20795221
TI  - Foreign Department.

PMID- 20795222
TI  - Provincial Medical & Surgical Journal.

PMID- 20795224
TI  - A Fatal Case of Hydrophobia: Treated with Chloroform.

PMID- 20795223
TI  - Lectures on the Diseases of Children: Delivered in the Chatham Street School of
      Medicine, Manchester.

PMID- 20795225
TI  - Remarks on the Effects of Iodine on the Glandular System, and on the Properties
      of Kousso.

PMID- 20795226
TI  - Case of Senile Gangrene: Treated by Local Bleeding.

PMID- 20795227
TI  - Hospital Reports.

PMID- 20795228
TI  - Foreign Department.

PMID- 20795229
TI  - Provincial Medical & Surgical Journal.

PMID- 20795231
TI  - On the Treatment of Incipient Hypertrophy of the Heart.

PMID- 20795230
TI  - Lectures on the Diseases of Children: Delivered in the Chatham Street School of
      Medicine, Manchester.

PMID- 20795232
TI  - On the Treatment of Diarrhoea and Dysentery by Sulphuric Acid.

PMID- 20795233
TI  - Case of Cancer of the Pylorus: Undetected during Life.

PMID- 20795234
TI  - Hospital Reports.

PMID- 20795236
TI  - Provincial Medical & Surgical Journal.

PMID- 20795235
TI  - Foreign Department.

PMID- 20795237
TI  - Lectures on the Diseases of Children: Delivered in the Chatham Street School of
      Medicine, Manchester.

PMID- 20795238
TI  - On the Diagnosis of Chronic Ovarian Tumours.

PMID- 20795239
TI  - Gallic Acid in Haemoptysis.

PMID- 20795241
TI  - Hospital Reports.

PMID- 20795240
TI  - On Mammary Abscess.

PMID- 20795242
TI  - Foreign Department.

PMID- 20795243
TI  - Provincial Medical & Surgical Journal.

PMID- 20795244
TI  - Lectures on the Diseases of Children: Delivered in the Chatham Street School of
      Medicine, Manchester.

PMID- 20795245
TI  - Case of Urethro-Vaginal, Recto-Vaginal Fistulae, and Calculus Vesicae.

PMID- 20795246
TI  - Hospital Reports.

PMID- 20795247
TI  - Foreign Department.

PMID- 20795248
TI  - Provincial Medical & Surgical Journal.

PMID- 20795249
TI  - On the Diagnosis of Chronic Ovarian Tumours.

PMID- 20795251
TI  - Hospital Reports.

PMID- 20795250
TI  - On Syphilis and Gonorrhoea.

PMID- 20795252
TI  - Foreign Department.

PMID- 20795253
TI  - Provincial Medical & Surgical Journal.

PMID- 20795255
TI  - On the Treatment of Cholera: By Calomel and Colocynth.

PMID- 20795254
TI  - Lectures on the Diseases of Children: Delivered in the Chatham Street School of
      Medicine, Manchester.

PMID- 20795256
TI  - Extraneous Substances in the Eye.

PMID- 20795257
TI  - Ipecacuanha as a Restorative.

PMID- 20795258
TI  - Draft Bill.

PMID- 20795259
TI  - Provincial Medical & Surgical Journal.

PMID- 20795260
TI  - On the Diagnosis of Chronic Ovarian Tumours.

PMID- 20795261
TI  - Case of Cancrum Oris: With Necrosis of a Large Portion of the Inferior Maxillary
      Bone, Followed by Recovery.

PMID- 20795262
TI  - Case of Abscess of the Right Ovary: Terminating in Rupture into the Peritoneum
      and Death from Peritonitis.

PMID- 20795263
TI  - Foreign Department.

PMID- 20795264
TI  - Provincial Medical & Surgical Journal.

PMID- 20795265
TI  - Lectures on the Diseases of Children: Delivered in the Chatham Street School of
      Medicine, Manchester.

PMID- 20795266
TI  - Cases of Hepatitis, Dysentery, and Diarrhoea: With Remarks.

PMID- 20795268
TI  - My Note Book: No. I.

PMID- 20795267
TI  - On Savine.

PMID- 20795270
TI  - Provincial Medical & Surgical Journal.

PMID- 20795269
TI  - Hospital Reports.

PMID- 20795271
TI  - Case of Strangulated Hernia.

PMID- 20795272
TI  - Death from the Formation of a Fibrinous Concretion in the Heart.

PMID- 20795273
TI  - Anomalous Case of Scrofulous Abscess of the Heart.

PMID- 20795274
TI  - Provincial Medical & Surgical Journal.

PMID- 20795276
TI  - Resistance training may make for a sharper mind.

PMID- 20795275
TI  - Health tips.  Stuck-ring strategies.

PMID- 20795277
TI  - MicroRNA. Regulators of gene function.

PMID- 20795278
TI  - Heart palpitations.  Often, but not always, harmless.

PMID- 20795279
TI  - Does car window glass block the sun's skin cancer-causing rays?

PMID- 20795280
TI  - Marriage and men's health.

PMID- 20795281
TI  - Psoriasis: more than skin deep.

PMID- 20795282
TI  - Health clubs: are they right for you?

PMID- 20795283
TI  - On call.  My 64-year-old wife was recently diagnosed with osteoporosis.  Her
      doctor said medication would help, and he reassured her that having osteoporosis
      was not all bad since it indicates a reduced risk for breast cancer.  I want to
      know if osteoporosis in men affects the risk of prostate cancer.

PMID- 20795284
TI  - On call.  I am a 78-year-old man with two medical problems, an enlarged prostate
      and cataracts.  I take Flomax for my prostate with good results, but I've been
      told that it can cause complications during cataract surgery.  Should I stop
      taking Flomax before I have surgery--and if so, what should I do about my
      prostate?

PMID- 20795285
TI  - The decline of religious holidays in old regime France (1642-1789).
AB  - Under the ancien regime individual bishops decided which official religious
      holidays, or fetes chomees, were observed in their dioceses. In the early
      seventeenth century there were on average 33 weekdays per year devoted to these
      holidays, but their number and choice varied widely across the country. From the
      mid-seventeenth century onwards French bishops began to eliminate many of these
      holidays, which were associated with drinking and idleness rather than with pious
      behaviour. These reforms initially encountered opposition from powerful interests
      in society, which limited their impact, but subsequently, and particularly after
      the mid-eighteenth century, the bishops' efforts were much more successful. By
      the end of the Old Regime the number of weekdays devoted to fetes chomees had
      declined to fewer than 20 in most of France. The process of reform also
      standardized religious practice as the same days were observed throughout the
      kingdom. Despite the royal government's lack of interest in the matter, a more
      uniform set of liturgical holidays replaced the regional diversity that had
      previously existed. The reformed ecclesiastical calendars were more closely
      geared to the seasonal pattern of agricultural labour and also reflected the
      Christocentrism of Tridentine Catholicism.

PMID- 20795286
TI  - Fleurs-de-lis in the forest: "absolute" monarchy and attempts at resource
      management in eighteenth-century France.
AB  - The notion of "resource management" has inspired some historians to rethink the
      nature of the state authority in early modern Europe. Like recent work on parts
      of Italy and Germany, this article investigates the development and
      implementation of legislation that sought to regulate the management and
      exploitation of forests. This was self-interested policymaking: as ancien regime
      France strove to match Britain's naval, colonial and maritime strength, the
      monarchy's priority was ship timbers. Yet the most sought-after pieces of wood
      were large, heavy and difficult to transport. According to standard accounts,
      such resources became rare during the eighteenth century, and the French navy
      turned increasingly to timber supplies from abroad. This article offers a wider
      view, by finding ways to analyse bureaucratic records created by the royal
      forestry officials (Eaux et Forets), which have been largely neglected by
      historians. A regional case study suggests that, besides extending the authority
      of royal agents to acquire timbers for the naval dockyards, the application of
      Louis XIV's Ordinance on Waterways and Forests (1669) generated huge amounts of
      information about the extent, nature and location of mature timber reserves
      across France.

PMID- 20795287
TI  - Philanthropies croisees: a joint venture in public health at Lyon (1917-1940).
AB  - Since the end of the First World War the Rockefeller Foundation has spearheaded a
      large-scale programme in the field of education for the health professions
      (doctors and nurses). In several countries throughout the world, but with its
      efforts concentrated on Europe, it has financed schools, constructed information
      networks, granted research scholarships and awarded training bursaries. In so
      doing it has not, however, been in the business of propagating an irresistible
      "American model," nor has it pursued a huge undertaking in disinterested aid.
      Through an attempt to contextualize these programmes, to bring to light the
      existence of common reference points, to retrace the work with local participants
      and to appraise cleavages within the philanthropic apparatus, this article
      proposes a fine-grained reading of the role of the Rockefeller Foundation at the
      Faculte de Medecine (Faculty of Medicine) and the Ecole d'Infirmieres et
      d'assistantes sociales (Training School for Nurses and Social Workers) in Lyon
      between 1917- and 1940. It analyses these institutions in terms of the
      transactions, negotiations and appropriations that highlight their joint-venture
      character and it identifies their varied impact.

PMID- 20795288
TI  - More lurid than lucid: the spiritualist invention of the world "sexism".
AB  - Nineteenth-century American spiritualists coined the word sexism long before its
      modern incarnation in order to refer to a complex of ideas about human sexuality
      and reproduction that were consonant with the general advancement of women's
      rights. Among these ideas was the belief that spirit and mind were ascendant over
      matter and could act directly on it. In their view, a woman's sensitive spiritual
      nature gave her the power to join spirit and matter. She could provide a way for
      exalted spirits to enter the world through her, in the mental character and even
      the physical form of her offspring, by focusing her own and others' spirits into
      the embryo growing within her, as if she were making a photograph. The goal of
      enhancing this ability would justify changing law and custom to ensure women's
      autonomy and freedom, especially to protect their decisions about sexual
      relations in order to regulate favorable and unfavorable impressions on the
      embryo. Emphasizing the embryo's sensitivity to spiritual impressions, however,
      also led some progressives to the conclusion that women's autonomy should be
      restricted. Women had to be kept away from even immaterial influences that would
      adversely affect them during pregnancy.

PMID- 20795289
TI  - Paul Braune confronts the National Socialists' "euthanasia" program.
AB  - On July 9, 1940, asylum director Paul Braune completed a twelve-page memorandum,
      or Denkschrift, on the National Socialists' T-4 "euthanasia" program. The
      memorandum identified three killing centers within a carefully planned, Reich
      wide program and summarized what Braune's research had uncovered about the fate
      of asylum patients at various T-4 facilities. Braune estimated that several
      thousand disabled people had been murdered between February and June 1940. After
      Protestant church leaders formally submitted Braune's memorandum to the Reich
      Chancellery, Braune was arrested by the Gestapo-pursuant to a direct order by
      Reinhard Heydrich-for having "sabotaged measures of the state in an irresponsible
      way." Despite Braune's protest, the killing of German asylum patients continued
      unabated. This article shows what a determined German citizen, assisted by an
      extensive network of information sources, was able to learn about the
      "euthanasia" program during the first six months of its implementation, and
      reveals the formidable difficulties that opponents of the program faced in their
      efforts to stop the killing of disabled people.

PMID- 20795291
TI  - Abstracts of the Canadian Nutrition Society's 9th Annual Scientific Meeting. June
      3-4, 2010, Alberta, Canada.

PMID- 20795290
TI  - Towards more uniform conflict disclosures: the updated ICMJE conflict of interest
      reporting form.

PMID- 20795292
TI  - Proceedings of the 24th Danube Congress of Psychiatry and the 12th Central
      European Neuropsychopharmacological Symposium. May 5-8, 2010, Zagreb, Croatia.

PMID- 20795294
TI  - Abstracts of the 5th Pannonian Symposium on CNS Injury. 13-15 May, 2010, Pecs,
      Hungary.

PMID- 20795293
TI  - Expansion, suspicion and the development of the International Committee of the
      Red Cross: 1939-45.
AB  - The International Committee of the Red Cross (ICRC) has often been maligned for
      its actions, or lack thereof, during the Second World War. In particular the
      Committee has been criticised for its apparent inability to compromise its
      mandate to provide impartial and non-politicised relief. This article discusses
      some of the problems of this interpretation of ICRC history by showing that,
      contrary to the image of the ICRC as a "well-meaning amateur", the Committee
      responded to the challenges of the Second World War with a series of bold
      initiatives that were crucial to the organisation's long-term development. Not
      only did these initiatives improve the success of the ICRC's humanitarian
      mission, but they also stand as testament to an organisation that, though devoid
      of diplomatic status and political power, was able to conduct its work whilst
      being restricted by the policies of belligerent governments and the physical
      dangers of total war.

PMID- 20795295
TI  - Trial run for Soviet food requisitioning: the expedition to Orel Province, fall
      1918.

PMID- 20795296
TI  - Creating cohesion from diversity: the challenge of collective identity formation
      in the global justice movement.
AB  - Collective identity formation is important because it plays a crucial role in
      sustaining movements over time. Studying collective identity formation in
      autonomous groups in the Global Justice Movement poses a challenge because they
      encompass a multiplicity of identities, ideologies, issues, frames, collective
      action repertoires, and organizational forms. This article analyzes the process
      of collective identity formation in three anti-capitalist globalization groups in
      Madrid, Spain, based on 3 years of ethnographic fieldwork. The author argues that
      for new groups practicing participatory democracy the regular face-to-face
      assemblies are the crucial arena in which collective identity can form and must
      be both effective and participatory in order to foster a sense of commitment and
      belonging. The article raises the possibility that scholars should consider what
      seems to be an oxymoron: the possible benefits of "failure" for social movements.

PMID- 20795298
TI  - Critical materialism: science, technology, and environmental sustainability.
AB  - There are widely divergent views on how science and technology are connected to
      environmental problems. A view commonly held among natural scientists and policy
      makers is that environmental problems are primarily technical problems that can
      be solved via the development and implementation of technological innovations.
      This technologically optimistic view tends to ignore power relationships in
      society and the political-economic order that drives environmental degradation.
      An opposed view, common among postmodernist and poststructuralist scholars, is
      that the emergence of the scientific worldview is one of the fundamental causes
      of human oppression. This postmodernist view rejects scientific epistemology and
      often is associated with an anti-realist stance, which ultimately serves to deny
      the reality of environmental problems, thus (unintentionally) abetting right-wing
      efforts to scuttle environmental protection. We argue that both the
      technologically optimistic and the postmodernist views are misguided, and both
      undermine our ability to address environmental crises. We advocate the adoption
      of a critical materialist stance, which recognizes the importance of natural
      science for helping us to understand the world while also recognizing the social
      embeddedness of the scientific establishment and the need to challenge the
      manipulation of science by the elite.

PMID- 20795302
TI  - [Abstracts of the 2nd FESNAD Congress, 3-5 March 2010, Barcelona, Spain].

PMID- 20795301
TI  - Abstracts of the XXXVII Annual Congress of the European Society for Artificial
      Organs, 8-11 September 2010, Skopje, Macedonia.

PMID- 20795303
TI  - Septate and scalariform junctions in arthropods.

PMID- 20795304
TI  - RE: Bi-unicondylar knee prosthesis: the steering knee.

PMID- 20795305
TI  - RE: Clinical applications of bone morphogenetic proteins: current evidence.
      Kanakaris, NK; Giannoudis, PV; JSOA 17(3):133-46, 2008.

PMID- 20795306
TI  - Monoclonal antibodies to Ki-67 protein suitable for immunohistochemical analysis.
AB  - Detection of cell proliferation index is widely used in experimental and clinical
      research. Earlier it was shown that nuclear Ki-67 protein expression is strictly
      related to cell proliferation. It was revealed during all active phases of the
      cell cycle in mammals but was absent in G0 phase, so Ki-67 presence in cell
      nuclei reflects a potential growth fraction of whole cell population. The main
      area of Ki-67 antibody application is in immunocytochemical and
      immunohistochemical analyses. The aim of our work was to generate mouse
      monoclonal antibodies for Ki-67 antigen detection in mammalian tissues and in
      cultured cells. His-tagged fragment of Ki-67 expressed in bacteria was used as an
      antigen. Antibody-producing hybridoma cells were generated by standard procedure
      by fusing SP2/0 myeloma cells with splenocytes of immunized mice. Monoclonal
      antibodies were analyzed using paraffin-embedded human melanoma tissue samples
      and breast cancer cell line MCF-7. It was shown that generated anti-Ki-67
      antibodies revealed proliferating cells in MCF-7 culture and after heat-induced
      epitope retrieval on paraffin sections of human melanoma tissue. In summary,
      generated antibodies could be useful for detection of proliferating cells in
      immunohistochemical and immunofluorescence studies of mammalian cells and
      tissues.

PMID- 20795307
TI  - Production and characterization of monoclonal antibody against Mycobacterium
      tuberculosis RpfB domain.
AB  - RpfB, one of the five resuscitation-promoting factors (Rpfs) produced by
      Mycobacterium tuberculosis (MTB), plays an important role in the resuscitation
      and growth of the dormant MTB. RpfB is likely the target antigen recognized by
      the host immune system. Studies have shown that Rpf genes exist in many bacteria
      and their encoded proteins all contain Rpf-like domain. It is likely that this
      domain has biological characteristics and immunogenicity similar to that of the
      complete Rpf protein. Therefore, RpfB domain protein from M. tuberculosis was
      selected for this study. Mice were subcutaneously immunized three times over 2
      week intervals. Mice splenocytes were then isolated and fused with SP20 cells.
      Hybridoma colonies were screened for monoclonal antibody (MAb) against RpfB
      domain. ELISA was used to examine the titer, specificity, and relative affinity
      of the antibody. The ability of produced anti-RpfB monoclonal antibody to
      recognize other proteins in the Rpf family and to inhibit the growth of
      Mycobacterium tuberculosis and Micrococcus luteus was examined. Our results
      showed that three anti-RpfB MAbs were successfully generated. All three MAbs can
      recognize RpfB domain specifically and can effectively inhibit the promoting
      effect of RpfB domain on the growth of MTB H37Ra strain and M. luteus at 1:1000
      dilution, indicating that anti-RpfB domain MAbs may inhibit the reactivation of
      dormant or latent MTB in vivo. Therefore, they may be able to prevent the
      recurrence of the occult infection. The production of anti-RpfB domain MAbs
      provides a powerful experimental tool to further study the biological and
      immunological characteristics of the RpfB domain and to evaluate the possibility
      of using RpfB domain as a candidate component for tuberculosis subunit vaccine.

PMID- 20795308
TI  - A primary school outbreak of pandemic 2009 influenza A (H1N1) in China.
AB  - BACKGROUND: We investigated the first known outbreak of pandemic 2009 influenza A
      (H1N1) at a primary school in China. OBJECTIVES: To describe epidemiologic
      findings, identify risk factors associated with 2009 H1N1 illness, and inform
      national policy including school outbreak control and surveillance strategies.
      METHODS: We conducted retrospective case finding by reviewing the school's
      absentee log and retrieving medical records. Enhanced surveillance was
      implemented by requiring physicians to report any influenza-like illness (ILI)
      cases to public health authorities. A case-control study was conducted to detect
      potential risk factors for 2009 H1N1 illness. A questionnaire was administered to
      50 confirmed cases and 197 age-, gender-, and location-matched controls randomly
      selected from student and population registries. RESULTS: The attack rate was 4%
      (50/1314), and children from all grades were affected. When compared with
      controls, confirmed cases were more likely to have been exposed to persons with
      respiratory illness either in the home or classroom within 7 days of symptom
      onset (OR, 4.5, 95% CI: 1.9-10.7). No cases reported travel or contact with
      persons who had traveled outside of the country. CONCLUSIONS: Findings in this
      outbreak investigation, including risk of illness associated with contacting
      persons with respiratory illness, are consistent with those reported by others
      for seasonal influenza and 2009 H1N1 outbreaks in school. The outbreak confirmed
      that community-level transmission of 2009 H1N1 virus was occurring in China and
      helped lead to changes in the national pandemic policy from containment to
      mitigation.

PMID- 20795310
TI  - Proceedings from the ONS (Oncology Nursing Society) 35th Annual Congress, San
      Diego, California, USA.

PMID- 20795309
TI  - Assessing physicians' in training attitudes and behaviors during the 2009 H1N1
      influenza season: a cross-sectional survey of medical students and residents in
      an urban academic setting.
AB  - BACKGROUND: Despite concern for hospital-based transmission of influenza, little
      research has been carried out on perceptions and behaviors of physicians in
      training with regard to influenza-like illness (ILI), especially in light of the
      recent H1N1 pandemic. OBJECTIVES: We aimed to evaluate self-reported episodes of
      ILI among medical students and residents to determine the impact of ILI on school
      and clinical performance, absenteeism, and patterns of preventive measures used
      by this population both in and out of the healthcare setting. METHODS: We
      anonymously surveyed medical students and residents at an urban institution
      between November 3 and December 11, 2009. Data were analyzed separately for
      medical students and residents for frequency of close-ended responses. Open-ended
      answers were analyzed thematically. Our Institutional Review Board exempted this
      study from review. RESULTS: Forty-five percent of medical students and 53% of
      resident respondents perceived the risk of acquiring H1N1 at school or work as
      high, and although 43% of medical students and 66% of resident respondents had
      received the influenza vaccination and most reported increasing non
      pharmaceutical preventive measures, 9% of medical students and 61% of residents
      with one or more episodes of ILI chose to continue to attend class or work when
      ill. CONCLUSIONS: Although students and residents report high risk of infection
      because of work- or school-related activities, many involved in patient care
      activities do not comply with recommended infection control precautions.
      Educational campaigns should be developed and infection control guidelines should
      be included in routine medical student and resident curricular activities.

PMID- 20795311
TI  - The Knops blood-group system: a review.

PMID- 20795312
TI  - Role for serial prenatal anti-Vel quantitative serologic monitoring with 2-ME
      serum treatment during pregnancy: case report.
AB  - Anti-Vel is an uncommon antibody to a high-prevalence antigen. Its clinical
      significance and management in the prenatal setting are not well characterized.
      We present a case that demonstrates the utility of serial prenatal anti-Vel
      quantitative serologic monitoring with 2-ME serum treatment during pregnancy. The
      patient is a 23-year-old Hispanic woman with history of prior pregnancy and prior
      transfusion who was discovered to have an antibody to the high-prevalence Vel
      antigen in the first trimester (week 7) of her second pregnancy. Interval
      measurements of the serologic antibody titers were performed during the next 26
      weeks. The untreated serum (IgM and IgG) titer increased from a baseline of 4 to
      16 during that interval, while the 2-ME (presumed IgG component) titer remained
      stable at 4. Responding to ultrasound findings suspicious for fetal anemia, the
      child was delivered without complications at 34 weeks' gestation. At birth, the
      DAT was negative and there was no evidence of HDN. Placed in the context of other
      similar reports, this case demonstrates the importance of separately reporting
      the IgG fraction (after either DTT treatment or 2-ME treatment) from the
      untreated (IgM and IgG) fraction and the importance of correlating the treated
      serum titer with potential clinical significance.

PMID- 20795313
TI  - Granulocyte serology: current concepts and clinical signifcance.
AB  - Applying serologic procedures to the detection of RBC and lymphocyte antigens has
      facilitated the identification of granulocyte antigens with established clinical
      significance, which are now classified in the human neutrophil antigen system.
      Granulocyte alloantibodies and autoantibodies have been implicated in a variety
      of clinical conditions including alloimmune neutropenia, autoimmune neutropenia,
      febrile and severe pulmonary transfusion reactions, drug-induced neutropenia,
      refractoriness to granulocyte transfusions, and immune neutropenia after
      hematopoietic stem cell transplantation. Although the intrinsically fragile
      nature of granulocytes contributes to the inherent challenges of granulocyte
      serology, several advances in laboratory procedures have improved detection of
      granulocyte antibodies. This review will provide a current perspective about the
      importance and use of granulocyte serology for detection of granulocyte
      antibodies that have significant medical effects.

PMID- 20795314
TI  - A review of the Colton blood group system.

PMID- 20795315
TI  - Alloimmunization to the D antigen by a patient with weak D type 21.
AB  - Antibodies of apparent D specificity may be found in D+ patients. We report a D+,
      multi-transfused Caucasian woman with myelodysplasia who exhibited several
      alloantibodies. One antibody was a moderately strong (2+) anti-D that persisted
      for 9 months, until the woman died. Molecular analysis of the patient's RHD gene
      identified the rare weak D type 21 (938C > T) allele. D alloantibodies do not
      occur in patients with most weak D types, but some patients with a weak D
      phenotype, including those with type 21, can produce antibodies to nonself
      epitopes of the wild-type D antigen.

PMID- 20795316
TI  - A review of the Chido/Rodgers blood group.
AB  - The C4 protein plays an important role in maintaining health and, in some
      situations complicated by poor expression of the C4 protein, may lead to or
      exacerbate certain diseases. The blood groups Chido and Rodgers are epitopes on
      the C4 protein, and polymorphisms associated with these epitopes may lead to the
      formation of antibodies to the Chido or Rodgers antigens in transfused patients.
      Identification of anti-Ch or anti-Rg is still based on the antibody
      neutralization with plasma from Ch-positive or Rg-positive individuals and lack
      of reactivity with qualified Ch-negative or Rg-negative RBCs. These antibodies
      may be useful in genetic studies of C4 polymorphisms or, in the case of C4
      deficient patients, a signal of the potential for serious illnesses. The
      recognition of the extreme polymorphism of the C4 gene and the gene complex RCCX
      should lead to more insights in the understanding of disease risk and potential
      treatment.

PMID- 20795317
TI  - Hox genes: studies from the 20th to the 21st century. Foreword.

PMID- 20795318
TI  - Hox genes: studies from the 20th to the 21st century. Preface.

PMID- 20795319
TI  - Regulation of Hox activity: insights from protein motifs.
AB  - Deciphering the molecular bases of animal body plan construction is a central
      question in developmental and evolutionary biology. Genome analyses of a number
      of metazoans indicate that widely conserved regulatory molecules underlie the
      amazing diversity of animal body plans, suggesting that these molecules are
      reiteratively used for multiple purposes. Hox proteins constitute a good example
      of such molecules and provide the framework to address the mechanisms underlying
      transcriptional specificity and diversity in development and evolution. Here we
      examine the current knowledge of the molecular bases of Hox-mediated
      transcriptional control, focusing on how this control is encoded within protein
      sequences and structures. The survey suggests that the homeodomain is part of an
      extended multifunctional unit coordinating DNA binding and activity regulation
      and highlights the need for further advances in our understanding of Hox protein
      activity.

PMID- 20795320
TI  - Cis-regulation in the Drosophila Bithorax Complex.
AB  - The discovery of the first homeotic mutation by Calvin Bridges in 1915 profoundly
      influenced the way we think about developmental processes. Although many
      mutations modify or deform morphological structures, homeotic mutations cause a
      spectacular phenotype in which a morphological structure develops like a copy of
      a structure that is normally found elsewhere on an organism's body plan. This is
      best illustrated in Drosophila where homeotic mutations were first discovered.
      For example, Antennapedia mutants have legs developing on their head instead of
      antennae. Because a mutation in a single gene creates such complete structures,
      homeotic genes were proposed to be key "selector genes" regulating the initiation
      of a developmental program. According to this model, once a specific
      developmental program is initiated (i.e., antenna or leg), it can be executed by
      downstream "realizator genes" independent of its location along the body axis.
      Consistent with this idea, homeotic genes have been shown to encode transcription
      factor proteins that control the activity of the many downstream targets to
      "realize" a developmental program. Here, we will review the first and perhaps,
      best characterized homeotic complex, the Bithorax Complex (BX-C).

PMID- 20795321
TI  - Maintenance of Hox gene expression patterns.
AB  - Once established, homeotic gene (Hox) expression is maintained in the original
      pattern by Polycomb-group (PcG) and trithorax-group (trxG) proteins therefore
      named maintenance proteins (MPs). PcG and trxG proteins maintain silencing and
      activation of Hox and many other genes, respectively. We provide here a brief
      overview of genetics and molecular biology of these proteins and of a third class
      of proteins termed Enhancers of Trithorax and Polycomb (ETP) that are required
      for both maintenance of silencing and activation of Hox genes. We examine the
      recruitment of MPs onto maintenance elements (MEs), their role in the regulation
      of transcription and the epigenetic marks that could provide maintenance. Lastly,
      we discuss two important roles of PcG proteins in replication of DNA and stem
      cell renewal and maintenance.

PMID- 20795322
TI  - Control of vertebrate Hox clusters by remote and global cis-acting regulatory
      sequences.
AB  - Despite apparently shared structural organisation and functional roles,
      vertebrate Hox genes are controlled by regulatory mechanisms rather distinct from
      those of the prototypic Drosophila Antennapedia (ANT-C) and Bithorax (BX-C)
      Complexes. If individual regulatory modules have been shown to recapitulate
      specific Hox expression patterns, other experimental studies underscore that
      vertebrate Hox clusters are controlled in many of their functions in a global
      manner, through distinct mechanisms. We will discuss the different models that
      have been proposed to account for these global regulatory modes. In this context,
      the studies of the regulation of the HoxD complex during limb development
      highlighted the role of global regulatory elements and the different mechanisms
      associated to transform a structural organisation into distinct temporal and
      spatial expression domains. We will further discuss how these mechanisms may have
      benefited from the structure of the vertebrate homeotic clusters and reciprocally
      contribute to shape their evolution towards an increased level of organisation
      and compaction.

PMID- 20795323
TI  - The early evolution of Hox genes: a battle of belief?
AB  - For more than a century the origin of metazoan animals and for less than three
      years the early evolution of Hox genes has been debated. Both discussions are
      intrinsically tied together. New data from whole genome sequencing and recent
      progress in phylogeny of basal metazoans allow to provide an answer. The
      evolution of diploblastic animals (Placozoa, Porifera, Ctenophora and Cnidaria)
      and Bilateria (all higher animals) went parallel. The early split of these two
      lineages led to the evolution of a Hox system in Bilateria and the presence of
      Hox-like genes in Cnidaria and Placozoa.

PMID- 20795324
TI  - Evolution of Hox complexes.
AB  - Recent years have seen a plethora of ideas and hypotheses, and lots of debate,
      about the origin and evolution of the Hox gene cluster. Here I will attempt to
      summarize these hypotheses, identify their strengths and weaknesses and highlight
      the types of new data that may lead to further resolution of the competing ideas.
      The major theme is that Hox genes originated very early in animal evolution and
      extensive independent duplications occurred in major lineages. Duplications
      however have not been the only route to change in the composition and structure
      of the Hox cluster, as extensive gene losses have occurred as well. Indeed it is
      gene loss that is one of the main obstacles in our understanding of the origin
      and evolution of Hox clusters. Matters should be improved with wider taxon
      sampling along with a clearer understanding of how duplicated genes evolve.

PMID- 20795325
TI  - The nematode story: Hox gene loss and rapid evolution.
AB  - The loss in some taxa of conserved developmental control genes that are present
      in the vast majority of animal lineages is an understudied phenomenon. It is
      likely that in those lineages in which loss has occurred it may be a strong
      signal of the mode, tempo and direction of developmental evolution and thus
      identify ways of generating morphological novelties. Intuitively we might expect
      these novelties to be particularly those associated with morphological
      simplifications. One striking example of this has occurred within the nematodes.
      It appears that over half the ancestral bilaterian Hox cluster has been lost from
      the model organism Caenorhabditis elegans and its closest related species.
      Studying the Hox gene complement of nematodes across the phylum has shown that
      many, if not all these losses occurred within the phylum. Other nematode clades
      only distantly related to C. elegans have additional Hox genes orthologous to
      those present in the ancestral bilaterian but absent from the model nematode. In
      some of these cases rapid sequence evolution of the homeodomain itself obscures
      orthology assignment until comparison is made with sequences from multiple
      nematode clades with slower evolving Hox genes. Across the phylum the
      homeodomains of the Hox genes that are present are evolving very rapidly. In one
      particular case the genomic arrangement of two homeodomains suggests a mechanism
      for gene loss. Studying the function in nematodes of the Hox genes absent from C.
      elegans awaits further research and the establishment of new nematode models.
      However, what we do know about Hox gene functions suggests that the genetic
      circuits within which Hox genes act have changed significantly within C. elegans
      and its close relatives.

PMID- 20795326
TI  - Are the deuterostome posterior Hox genes a fast-evolving class?
AB  - There has been a great deal of interest in analysing the molecular evolution of
      the Hox cluster using both bioinformatic and experimental approaches. The
      posterior Hox genes have been of particular interest to both groups of biologists
      for a number of reasons: they appear to be associated with the evolution of a
      number of morphological novelties; the protostomes appear to be have lost a
      highly-conserved and functionally important amino acid motif (the hexapeptide
      motif) from their posterior Hox genes; and deuterostome posterior Hox genes seem
      to be evolving more quickly than all other Hox genes. In this chapter I will
      discuss the last of these points. The idea that Deuterostome posterior Hox genes
      were evolving more quickly than other Hox genes was first suggested by David
      Ferrier and colleagues. In this chapter, I start by introducing the posterior Hox
      genes--their distribution among the animal phyla and the likely sequence of
      duplications that led to this distribution. I then introduce the idea of
      'deuterostome posterior flexibility' and examine this hypothesis in light of more
      recent phylogenetic and genomic work on the Hox cluster. Finally, I discuss some
      new approaches that could be used to test directly for differential rates of
      evolution among Hox genes and to assess what might underlie these differences.

PMID- 20795327
TI  - Hox genes and the body plans of chelicerates and pycnogonids.
AB  - Hox genes are found in all metazoan phyla and are involved in specifying identity
      along the anterior-posterior body axis. In arthropods, ten different classes of
      Hox genes can be distinguished, which are expressed in a typical staggered array
      along the anterior-posterior axis of the embryo in characteristically stable
      domains. These features have been used to align segments between different
      arthropod groups and in this way have contributed to solving longstanding
      zoological questions. In this chapter I summarize Hox gene data from
      chelicerates, including the enigmatic pycnogonids (sea spiders) and how these
      data have helped us to understand the body plans of different arthropod taxa.

PMID- 20795328
TI  - Hox3/zen and the evolution of extraembryonic epithelia in insects.
AB  - Insects have undergone dramatic evolutionary changes in extraembryonic
      development, which correlate with changes in the expression of the class-3 Hox
      gene zen. Here, we review the evolution of this gene in insects and point out how
      changes in zen expression may have affected extraembryonic development at the
      morphological and the genetic level.

PMID- 20795329
TI  - Hox genes and brain development in Drosophila.
AB  - Hox genes are prominently expressed in the developing brain and ventral ganglia
      of Drosophila. In the embryonic brain, the Hox genes labial and Deformed are
      essential for the establishment of regionalized neuronal identity; in their
      absence cells are generated in the brain but fail to acquire appropriate neuronal
      features. Genetic analyses reveal that Hox proteins are largely equivalent in
      their action in embryonic brain development and that their expression is under
      the control of cross-regulatory interactions among Hox genes that are similar to
      those found in embryogenesis of trunk segments. Hox genes have a different role
      in postembryonic brain development. During the larval phase of CNS development,
      reactivation of specific Hox genes terminates neural proliferation by induction
      of apoptotic cell death in neural stem cell-like progenitors called neuroblasts.
      This reactivation process is tightly controlled by epigenetic mechanisms
      requiring the Polycomb group of genes. Many features of Hox gene action in
      Drosophila brain development are evolutionarily conserved and are manifest in
      brain development of vertebrates.

PMID- 20795331
TI  - Fatigue, performance, and overtraining.

PMID- 20795330
TI  - Homeosis and beyond. What is the function of the Hox genes?
AB  - What is the function of the Hox genes? At first glance, it is a curious question.
      Indeed, the answer seems so obvious that several authors have spoken of 'the Hox
      function' about some of the Hox genes, namely Hox3/zen and Hox6/ftz that seem to
      have lost it during the evolution of Arthropods. What these authors meant is that
      these genes have lost their 'homeotic' function. Indeed, 'homeotic' refers to a
      functional property that is so often associated with the Hox genes. However, the
      word 'Hox' should not be used to refer to a function, but to a group of genes.
      The above examples of Hox3/zen (see Schmitt-Ott's chapter, this book) and
      Hox6/ftz show that the homeotic function may be not so tightly linked to the Hox
      genes. Reversely, many genes, not belonging to the Hox group, do present a
      homeotic function. In the present chapter, I will first give a definition of the
      Hox genes. I will then ask what is the 'function' of a gene, examining its
      various meanings at different levels of biological organization. I will review
      and revisit the relation between the Hox genes and homeosis. I will suggest that
      their morphological homeotic function has been secondarily derived during the
      evolution of the Bilateria.

PMID- 20795332
TI  - Wolfgang Amadeus Mozart--controversies regarding his illnesses and death: a
      bibliographic review.
AB  - More has been written about Mozart's illnesses and death than for any other
      composer. An exploration of PAMA's Bibliography of Performing Arts Medicine
      provides the data for this review. The bibliography contained 136 entries that
      pertained to Wolfgang Amadeus Mozart. Of these, 81 were available to the author,
      either in printed or electronic copy. In order to provide a clearer historical
      perspective on this topic, this review assembles information pertaining to
      illnesses and other medical problems that occurred during Mozart's life as well
      as those purportedly contributing to his death.

PMID- 20795333
TI  - Health promotion and prevention in higher music education: results of a
      longitudinal study.
AB  - OBJECTIVES: Music-related symptoms can already be found among student musicians
      during their years of university training. The goals of the present study were to
      ascertain the state and developmental course of the student musicians' health and
      to test the effectiveness of a preventive curriculum given to student musicians
      during their first two semesters at university. METHODS: Within a longitudinal,
      observational study, we assessed students' psychological and physical health
      during the first 2 years of university training. We compared data from the group
      of students who had followed the prevention program (intervention group, IG, n =
      144) with data of a comparison group (CG, n = 103) of students who had not
      followed the program. Using standardized questionnaires, we measured physical and
      psychological symptoms as well as health behavior in a sequential plan (duration,
      3.5 yrs). RESULTS: Student musicians (n = 247) showed elevated ratings in
      psychological and physical health in comparison with nonmusicians of the same
      age. These ratings decreased at the end of the students' second year. The
      prevention program had a preventive effect on the students' psychological health:
      while IG students remained stable in their performance and powers of
      concentration, CG students got worse in those same areas. However, the prevention
      program did not reduce physical symptoms. In comparison with their younger
      colleagues, upper-level students took more courses in body-oriented methods,
      relaxation, and mental techniques, which focus on preventive measures for
      musicians. CONCLUSION: At present, the study offers evidence supporting the use
      of the prevention curriculum for young musicians. In higher music education,
      preventive education has a positive impact on students' performance and their
      attitude toward health. The preventive curriculum does not have an effect on
      preexisting physical symptoms, and those symptoms related to the students
      musicians' activity should rather be treated in an additional therapeutic
      setting.

PMID- 20795334
TI  - Quantifying the physical demands of a musical performance and their effects on
      performance quality.
AB  - This study investigated the effects of fatigue on performance quality induced by
      a prolonged musical performance. Ten participants prepared 10 min of repertoire
      for their chosen wind instrument that they played three times consecutively.
      Prior to the performance and within short breaks between performances,
      researchers collected heart rate, respiratory rate, blood pressure, blood lactate
      concentration, rating of perceived exertion (RPE), and rating of anxiety. All
      performances were audio recorded and later analysed for performance errors.
      Reliability in assessing performance errors was assessed by typical error of
      measure (TEM) of 15 repeat performances. Results indicate all markers of physical
      stress significantly increased by a moderate to large amount (4.6 to 62.2%; d =
      0.50 to 1.54) once the performance began, while heart rate, respirations, and RPE
      continued to rise by a small to large amount (4.9 to 23.5%; d = 0.28 to 0.93)
      with each performance. Observed changes in performance between performances were
      well in excess of the TEM of 7.4%. There was a significant small (21%, d = 0.43)
      decrease in errors after the first performance; after the second performance,
      there was a significant large increase (70.4%, d = 1.14). The initial increase in
      physiological stress with corresponding decrease in errors after the first
      performance likely indicates "warming up," while the continued increase in
      markers of physical stress with dramatic decrement in performance quality likely
      indicates fatigue. Musicians may consider the relevance of physical fitness to
      maintaining performance quality over the duration of a performance.

PMID- 20795335
TI  - Injuries in students of three different dance techniques.
AB  - As with any athlete, the dancer has a high risk for injury. Most studies carried
      out relate to classical and modern dance; however, there is a lack of reports on
      injuries involving other dance techniques. This study is an attempt to determine
      the differences in the incidence, the exposure-related rates, and the kind of
      injuries in three different dance techniques. A prospective study about dance
      injuries was carried out between 2004 and 2007 on students of modern, Mexican
      folkloric, and Spanish dance at the Escuela Nacional de Danza. A total of 1,168
      injuries were registered in 444 students; the injury rate was 4 injuries/student
      for modern dance and 2 injuries/student for Mexican folkloric and Spanish dance.
      The rate per training hours was 4 for modern, 1.8 for Mexican folkloric, and 1.5
      injuries/1,000 hr of training for Spanish dance. The lower extremity is the most
      frequent structure injured (70.47%), and overuse injuries comprised 29% of the
      total. The most frequent injuries were strain, sprain, back pain, and
      patellofemoral pain. This study has a consistent medical diagnosis of the
      injuries and is the first attempt in Mexico to compare the incidence of injuries
      in different dance techniques. To decrease the frequency of student injury, it is
      important to incorporate prevention programs into dance program curricula. More
      studies are necessary to define causes and mechanisms of injury, as well as an
      analysis of training methodology, to decrease the incidence of the muscle
      imbalances resulting in injury.

PMID- 20795336
TI  - Comparative analysis of substance use in ballet, dance sport, and synchronized
      swimming: results of a longitudinal study.
AB  - There have been few studies comparing substance use and misuse (SU&M) in
      different performing arts forms. Herein, we identified and compared SU&M in women
      studying an art (ballet, n = 21), a non-Olympic sport (dance sport, n = 25), and
      an Olympic sport (synchronized swimming, n = 23). The sample of variables
      comprised general, educational, and sport factors, as well as SU&M data,
      including consumption of opiates, cigarettes, alcohol, nutritional supplements,
      doping behaviors, and beliefs. Using the Kruskal-Wallis test, we found no
      significant differences between study groups in potential doping behaviors. Most
      of the examinees reported that they did not rely on physicians' and/or coaches'
      opinions regarding doping. Only sport dancers recognized their consumption of
      cannabis as a violation of anti-doping rules. Those more convinced that doping
      habits are present in their sport (or art) have a certain tendency toward doping
      usage. In conclusion, a strong anti-doping campaign within the studied arts is
      suggested, focusing on the health-related problems of SU&M.

PMID- 20795337
TI  - Effects of using relaxation breathing training to reduce music performance
      anxiety in 3rd to 6th graders.
AB  - The current study examined the effects of applying relaxation breathing training
      (RBT) as a means to reduce music performance anxiety (MPA) in young, talented
      musicians. A group of 59 young musicians from 3rd to 6th grade participated in
      this study, and all of them started RBT twice a week for 2 months prior to the
      examination. Four tests--2 mos, 1 mos, half an hour and 5 min before the
      examination--were conducted to examine the level of MPA after the application of
      RBT. Results show that the degree of MPA 5 min before the trial was lower than
      the degree of performance anxiety half an hour before the jury (t = -3.683, p <
      0.01), which indicated that the RBT was associated with a decrease in MPA.
      Although a series of RBT exercises was applied, results indicated that when
      approaching the date of examination, the degree of performance anxiety still
      increased and reached its maximum half an hour before the jury. The
      recommendation for future studies is to combine the application of RBT with other
      methods to expand its effect in reducing MPA.

PMID- 20795338
TI  - Utility of chromosomal chromogenic in situ hybridization as an alternative to
      flow cytometry and cytogenetics in the diagnosis of early partial hydatidiform
      moles: a validation study.
AB  - OBJECTIVE: The introduction of p57 immunohistochemistry has aided the distinction
      between early complete moles (CMs) and hydropic abortus (HA), but no single
      technique has emerged for the distinction between early partial moles (PMs) and
      HA. Flow cytometry and cytogenetics have been used, but these require specialized
      equipment/expertise. The goal of this study is validation of chromosome in situ
      hybridization (CrISH), focusing on comparing the results to those obtained by
      cytogenetic methods. STUDY DESIGN: Archival paraffin blocks from molar and
      nonmolar gestations were retrieved. Sections were labeled with a chromosome 10
      probe. Hybridization and visualization were performed using standard protocols.
      One hundred nuclei per sample were scored for the number ofsignals. RESULTS: Of
      50 hydatidiform moles, 22 were PMs and 28 were CMs. The CMs showed 2 signals in
      25 cases and 4 signals in 3 cases. The PMs showed 3 signals in 21 cases and 2
      signals in 1 case. For the HAs there were 2 signals in 24 cases, and 1 case had 3
      signals. Concordance between CrISH and flow cytometry studies for molar
      gestations was 95%. CONCLUSION: CrlSH is a highly effective adjunct in
      differentiating between PM and CM and between PM and HA. CrlSH is a simple, cost
      effective adjunct in evaluating molar gestations.

PMID- 20795339
TI  - Low-risk gestational trophoblastic neoplasia and methotrexate resistance:
      predictors of response to treatment with actinomycin D and need for combination
      chemotherapy.
AB  - OBJECTIVE: To determine whether any clinical parameters predict the need for
      multiagent chemotherapy for treatment of low-risk gestational trophoblastic
      neoplasia (GTN) after the development of methotrexate (MTX) resistance. STUDY
      DESIGN: We retrospectively analyzed clinical data from the New England
      Trophoblastic Disease Center from women with post-molar GTN between 1973 and
      2003. RESULTS: We analyzed data from 150 women (40 with partial mole, 110 with
      complete mole) who received single-agent MTX for low-risk GTN using FIGO and WHO
      scoring systems. Of the 45 women who developed MTX resistance, the majority
      (37/45) of these patients received actinomycin D, with 10 patients ultimately
      requiring multiagent chemotherapy. The requirement for multiagent chemotherapy
      following MTX resistance was associated with a beta-hCG > 600 mlU/mL 1 week
      following initial MTX therapy (p < 0.03). Conversely, a beta-hCG < 600 mlU/mL 1
      week following initial MTX therapy was as-sociated with a 93% probability of
      remission with actinomycin D alone. All patients went into durable remission.
      CONCLUSION: The prognosis for patients with low-risk GTN following molar
      gestation is excellent, with 100% remission rate, though a small but significant
      proportion (7%) required multiagent chemotherapy. The need for multiagent
      chemotherapy was associated with beta-hCG levels 1 week following initial MTX
      therapy.

PMID- 20795340
TI  - Differences in total human chorionic gonadotropin immunoassay analytical
      specificity and ability to measure human chorionic gonadotropin in gestational
      trophoblastic disease and germ cell tumors.
AB  - OBJECTIVE: To determine the ability of several radioimmunoassays and commercial
      two-site immunoassays to detect the first World Health Organization International
      Reference Reagents (IRRs) for 6 defined human chorionic gonadotropin (hCG)
      variants and to compare their performance in measuring hCG in sera from patients
      with gestational trophoblastic disease (GTD) and germ cell tumors (GCTs) of the
      testis or ovary. STUDY DESIGN: The reactivity of the different assays with the 6
      IRRs together with the current fourth International Standard (IS, 75/589) was
      tested using 5 commercial two-site assays as well as 2 competitive polyclonal
      radioimmunoassays (RIAs) and a competitive monoclonal immunoassay. Individual
      samples from 41 patients (19 GCT and 22 GTD) with high circulating levels of hCG
      (range, 718-6,055,000 IU/L) were diluted and measured using the various
      immunoassays. RESULTS: The results of 4 GCT patient samples varied markedly among
      the assays, including 1 sample that was grossly underestimated by 3 of the
      commercial assays. CONCLUSION: Comparison of each assay's reactivity to the
      variant isoforms revealed that recognition of the isoforms was highly variable,
      particularly for hCGbeta and hCGbeta core fragment (hCGbetacf).

PMID- 20795341
TI  - Management of drug resistant gestational trophoblastic neoplasia.
AB  - OBJECTIVE: To determine the outcome of secondary management in drug-resistant
      gestational trophoblastic neoplasia (GTN). STUDY DESIGN: Sixteen of 60 patients
      with GTN (8 low-risk and 8 high-risk) who developed resistance to primary
      chemotherapy were studied retrospectively. Primary chemotherapy was methotrexate
      folinic acid rescue (MTX-FA) for low risk and etoposide/methotrexate/actinomycin
      D/cyclophosphamide/vincristine (EMA-CO) for high risk. Secondary chemotherapy for
      the low-risk group was either actinomycin D or EMA-CO, depending on serum beta
      human chorionic gonadotropin (hCG) levels at resistance. For the high-risk group,
      etoposide/methotrexate/actinomycin D/cisplatinum (EMA-EP) or
      bleomycin/etoposide/cisplatin (BEP) was given. Third-line chemotherapy was
      vincristine/actinomycin D/cyclophosphamide (VAC) or vincristine/
      iphosphamide/cisplatin (VIP). Surgery and radiotherapy were used in selected
      patients. RESULTS: Survival after salvage therapy in low-risk patients was 100%:
      2 with EMA-CO and 6 with actinomycin D. Of high-risk cases 75% were cured with
      EMA-EP or BEP. Third-line chemotherapy was given in 2 patients: 1 was lost to
      follow-up and the other died. Survival was significantly influenced by both hCG
      level at the start of secondary therapy and site of metastasis. CONCLUSION:
      Prognosis in GTN is excellent. Optimization of treatment strategies for those who
      develop drug resistance remains a key challenge.

PMID- 20795342
TI  - Screening for central nervous system disease in metastatic gestational
      trophoblastic neoplasia.
AB  - OBJECTIVE: To evaluate the Sheffield Trophoblastic Tumour Centre protocol for
      central nervous system (CNS) involvement in high-risk patients with gestational
      trophoblastic neoplasia (GTN) and determine the impact of brain imaging and
      lumbar puncture (LP) results on subsequent clinical care. STUDY DESIGN: The
      trophoblastic tumor database was searched for patients fitting any of the
      following criteria registered between January 1, 1988, and December 31, 2008: hCG
      levels > 50,000 IU/L, high risk, > or = 2 for metastases. Placental site
      trophoblastic tumors (PSTTs) were excluded, and all patients with signs or
      symptoms suggestive of CNS involvement were investigated. Patients were to have
      computed tomography (CT) scan of the head and, if not contraindicated, LP to
      determine the ratio of cerebrospinal fluid to blood hCG level. RESULTS: A total
      of 154 patients met > or = 1 of the defined criteria for CNS investigation. In 7
      patients there was evidence of CNS involvement on CT. Only 2 cases had no
      clinical evidence of CNS disease-both had very-high-risk choriocarcinoma. No
      diagnosis of CNS disease was made on LP alone. CONCLUSION: We propose that in the
      absence of neurologic symptoms or signs, only patients with choriocarcinoma need
      be screened. Magnetic resonance imaging head scan is preferred as the most
      sensitive and safe technology available.

PMID- 20795343
TI  - Geographical distribution and demographic characteristics of gestational
      trophoblastic disease.
AB  - OBJECTIVE: To outline the geographical distribution pattern of gestational
      trophoblastic disease (GTD) in a referral center in Bahia, Brazil, and determine
      the demographics of the disease. STUDY DESIGN: We conducted a study of data
      retrieved from medical records of 140 GTD patients referred to our Trophoblastic
      Diseases Center in 2002-2007, assessing geographical distribution across health
      care districts, demographics, referral sources, and previous pregnancy status.
      RESULTS: The most common GTD types were hydatidiform mole (106, 75.7%), invasive
      mole (32, 22.9%), choriocarcinoma (1, 0.7%), and placental site trophoblastic
      tumor (1, 0.7%). GTD incidence was 8.5 in 1,000 deliveries. Most patients
      originated from the coastal region (East district), which includes the state
      capital (77.9%). The 20-34 age group predominated (65%). Education level (67.9%
      attended elementary school only) and employment rate (42.9%) were low. Secondary
      hospitals were the principal source of referral (84.3%), followed by self
      referrals (15.7%). Regarding previous pregnancy status, 42.1% (n = 59) had had
      term pregnancy, 39.3% (n = 55) no pregnancy, 15% (n = 21) miscarriage, and 0.7%
      (n = 1) ectopic pregnancy; 4 patients (2.9%) had previous hydatidiform mole.
      CONCLUSION: GTD predominated in the peak fertility age group and among patients
      of unfavorable sociodemographic status.

PMID- 20795344
TI  - Primary pulmonary choriocarcinoma after human chorionic gonadotropin
      normalization following hydatidiform mole: a report of two cases.
AB  - BACKGROUND: Primary pulmonary choriocarcinoma (PPC) is rare and frequently leads
      to death. CASES: Two young patients presented with previous molar pregnancy and
      spontaneous serum human chorionic gonadotropin (hCG) normalization. Patient 1 was
      referred to our center after partial response to chemotherapy. Pulmonary
      lobectomy was performed, and hCG rapidly declined. During further chemotherapy,
      liver metastasis was detected by positron emission tomography. Right hepatectomy
      was performed, and hCG declined for 28 days, but increased again despite
      chemotherapy. This patient died from hepatic failure 3 years after diagnosis.
      Patient 2 presented with persistently high hCG, though the affected organ was not
      identified. Chemotherapy was unsuccessful. Patient reevaluation showed an
      isolated pulmonary mass. Pulmonary lobectomy was performed; 2 weeks later, hCG
      was normal and consolidation with 2 cycles of chemotherapy was administered. The
      patient has been in remission for 24 months. PPC was confirmed by histopathology
      and immunohistochemistry in both cases. Gestational origin of the tumor was
      confirmed by molecular genetic analysis (polymorphic microsatellite markers).
      CONCLUSION: The possibility of choriocarcinoma cannot be overlooked in young
      women with an isolated pulmonary mass. Early diagnosis, prompt chemotherapy, and
      surgical resection in a specialized center improves the prognosis.

PMID- 20795345
TI  - Recurrent gestational trophoblastic disease in a case of suspected quiescent
      gestational trophoblastic disease: a case report.
AB  - BACKGROUND: In Japan there are no reported cases of phantom human chorionic
      gonadotropin (hCG) or quiescent gestational trophoblastic disease (GTD). GTD is
      managed well in Japan according to Japanese guidelines for the treatment of GTD,
      and we have almost conquered this disease during recent decades. Furthermore, the
      incidence of GTD is decreased today, associated with the decrease of birth rate
      in Japan. Many young doctors now have little opportunity to see typical classic
      mole and participate in the management of GTD during their residency training.
      This case is the first case of suspected quiescent GTD in Japan and was referred
      to us for further evaluation. After careful evaluation, including measurement of
      hyperglycosylated hCG, we concluded that this case was not a quiescent GTD but
      recurrent GTD. CASE: The patient was a 46-year-old woman, G3, P2, A1, who
      underwent dilation and curettage for complete mole 7 years earlier. hCG elevated
      during follow-up, and a 50-mg methotrexate single injection was given. hCG
      decreased to 20-30 mIU/mL, but it then plateaued for 3 months. Etoposide 100
      mg/m2/day was then given for 5 days, and hCG became undetectable. Three years and
      3 months later beta-hCG went up to 3.1 ng/mL, but magnetic resonance imaging and
      computed tomography scans did not show any evidence of tumor. The patient was
      referred to us as a case of suspected quiescent GTD for further evaluation.
      CONCLUSION: After thorough evaluation we concluded that this case was not a
      quiescent GTD but a recurrent GTD. We emphasize that sufficient initial
      chemotherapy is very important to reduce the risk of recurrence.

PMID- 20795346
TI  - Quality of life of gestational trophoblastic neoplasia survivors: a study of
      patients at the Philippine General Hospital trophoblastic disease section.
AB  - OBJECTIVE: To evaluate the quality of life (QOL) of patients who were diagnosed
      with gestational trophoblastic neoplasia (GTN) at the Philippine General Hospital
      Trophoblastic Disease Section and who were in remission at the time of this
      study. STUDY DESIGN: A cross-sectional descriptive study designed to measure the
      QOL of all patients diagnosed as having GTN in remission and following up at the
      Philippine General Hospital Trophoblastic Disease Outpatient Clinic from May
      August 2008 (N = 46). This study used the short form 12-question (SF-12) survey
      forms to evaluate the QOL of patients diagnosed with GTN. Scores from the SF-12
      were analyzed using Pearson's correlation. Statistical significance was assumed
      for p values < 0.05 and 0.01 for all statistical tests. RESULTS: Forty-six GTN
      survivors included in the study successfully answered all the questions. Using
      Pearson's correlation of demographic characteristic variables and SF-12 domains,
      it was found that there was better physical functioning among younger patients,
      and there was mild limitation in moderate activities during a typical day among
      older patients. There was a significant positive correlation between educational
      level and physical functioning. A negative correlation was found between the
      stage of GTN and patients' general health. In conclusion, the survivors' age,
      educational level and type of treatment had impact on the QOL among GTN survivors
      in terms of physical functioning. No relationship was established between the
      demographic variables and mental status. CONCLUSION: SF-12 appears to be a
      reliable instrument, suggesting its potential in measuring health status in GTN
      survivors. Age, educational attainment and type of treatment were shown to have
      an impact on the QOL of the surviving GTN patients.

PMID- 20795347
TI  - Use of complementary and alternative medicines among women with gestational
      trophoblastic diseases: a survey at the Philippine General Hospital.
AB  - OBJECTIVE: To determine the prevalence of complementary and alternative medicine
      (CAM) use among women with gestational trophoblastic disease (GTD) at the
      University of the Philippines-Philippine General Hospital (UP-PGH). STUDY DESIGN:
      A survey on the use of CAM among women (N = 52) with GTD managed at the UP-PGH
      Gestational Trophoblastic Disease Center from June to August 2009 was done.
      RESULTS: The mean age of the participants was 32.3 years, and there were no
      significant differences in the proportion of CAM users as to educational
      attainment, diagnosis and treatment type received. Among the participants 96%
      used CAM, most commonly mental healing/prayer, fruit juices/vegetable diet,
      banaba/taheebo tea and multivitamins. Reasons for CAM use included safety,
      improvement of immune system, stress reduction and hope for their condition.
      Benefits included enhanced quality of life, stress reduction, immune system
      improvement and a healthier lifestyle. No untoward effect of CAM use was
      reported. Thirty-six percent of the participants disclosed CAM use to their
      physician. About 56% percent of the physicians were in favor of the CAM used. The
      main sources of information on CAM were relatives and friends. CONCLUSION: To
      better address patients' needs, physicians should routinely ask patients about
      their use of CAM and be able to discuss these therapies with them.

PMID- 20795348
TI  - High-risk gestational trophoblastic neoplasia at Gujarat Cancer and Research
      Institute: thirteen years of experience.
AB  - OBJECTIVE: To evaluate and analyze the results of chemotherapy (EMA-CO
      [etoposide, methotrexate, actinomycin D-cyclophosphamide, vincristine]) in high
      risk gestational trophoblastic neoplasia (GTN). STUDY DESIGN: A total of 97 women
      with high-risk GTN were evaluated for a period of 13 years (1995-2008). All women
      received EMA-CO as a first-line chemotherapy. EMA-EP (etoposide, methotrexate,
      actinomycin and cisplatinum), PVB (cisplatin, vinblastine and bleomycin), and BEP
      (bleomycin, etoposide and cisplatin) were the chemotherapies used as second-line
      therapy in women who experienced resistance to primary chemotherapy. Intrathecal
      methotrexate was given in women with brain metastasis and also as prophylaxis in
      pulmonary metastasis. Eleven women had brain metastasis and received cranial
      radiotherapy. The most common toxicity was hematologic. . RESULTS: Of 97 women,
      78 (80.4%) were evaluable and 19 (19.6%) were lost to follow-up with incomplete
      treatment. Of the 78 patients, 6 women developed resistance and had progression
      of disease. Seven women had died (5 due to disease, 2 due to chemotherapy
      toxicity). Overall 65 of the 78 (83.3%) women achieved remission. Of the 78
      women, 66.7% (52/78) had complete remission with first-line chemotherapy, and an
      additional 16.6% (13/78) achieved remission with second-line chemotherapy,
      resulting in a total of 83.3% (65/78) attaining remission. A total of 46% (30/
      65) had follow-up of > 3 years, and 32.4% (21/65) had follow-up of 1-3 years.
      Three of 9 women with brain metastasis achieved remission. Sixty percent (39/65)
      resumed normal menstrual function (had remission for at least 2 years). Twelve
      women became pregnant since the completion of the chemotherapy, with 10 live
      births of healthy infants without any congenital abnormalities. CONCLUSION: High
      risk GTNs are highly curable if properly treated, and patients can anticipate a
      normal future reproductive outcome. EMA-CO remains the preferred chemotherapy for
      management.

PMID- 20795349
TI  - The demographics of molar pregnancies in England and Wales from 2000-2009.
AB  - OBJECTIVE: To analyze the overall incidence of molar pregnancies and that of
      complete and partial molar pregnancies across the reproductive age range for
      England and Wales for the period 2000-2009. STUDY DESIGN: The cases of all
      patients with molar pregnancies registered with the UK Trophoblast disease
      service from England and Wales were identified. The overall number of molar
      pregnancies registered from 1998-2007 was compared to the number of maternities
      (live births and still births) and total viable conceptions for each year. For
      the series 2000-2009 the number of complete and partial molar pregnancies were
      compared to the number of maternities and terminations occurring for women across
      the age range < 14 to 50+ years, allowing an accurate estimate of the risk of
      molar pregnancy for women conceiving at any age. RESULTS: The results indicate
      that for the period 1998-2007 the overall incidence of molar pregnancies was 1
      case per 591 viable conceptions. The incidence increased from 1:611 in 1997 to
      1:528 in 2008. The age-specific data for the period 2000-2009 confirms a risk
      level of < 0.2%for women aged 18 {N dash} 39 years, with a modest excess risk for
      young teenagers but a much more significant increase for women > 40, where the
      risk is 1% at 45 and 17% at > or = 50. CONCLUSION: This study provides detailed
      data regarding the risk of partial and complete molar pregnancies with increasing
      maternal age. It confirms that the risk of partial molar pregnancy varies
      relatively little with age, with complete molar pregnancies contributing the main
      component of the overall increase with age.

PMID- 20795350
TI  - Effect of cigarette smoking on epithelial ovarian cancer survival.
AB  - OBJECTIVE: To determine associations between smoking and survival in patients
      with ovarian cancer. STUDY DESIGN: We performed a retrospective review of
      patients undergoing surgery for ovarian cancer. Abstracted patient data included
      age, smoking history, stage, grade, extent of cytoreduction, and survival. Data
      were examined with Fisher's exact test, Kaplan-Meier survival analysis, and Cox
      regression analysis. RESULTS: A total of 130 patients met criteria for review.
      Seventeen (13%) smoked cigarettes at the time of initial laparotomy. Twenty-one
      (16%) were left with > 1 cm residual disease. Smoking did not correlate with the
      incidence of suboptimal cytoreduction. There were no statistical differences in
      incidence of hypertension, obesity, or coronary artery disease in smokers
      compared to nonsmokers. Smoking was found to negatively influence length of
      progression-free survival. Similarly, smokers were found to have decreased
      disease-specific overall survival compared to nonsmokers. Cigarette smoking
      retained independent significance as poor prognostic factors, after controlling
      for age, stage, and grade. CONCLUSION: These findings identify a negative
      correlation with cigarette smoking and survival in women with ovarian cancer.
      Further studies are proposed to elucidate the molecular mechanisms underlying
      these clinical observations.

PMID- 20795351
TI  - Effect of patient age on outcomes and compliance in women with minimally abnormal
      pap tests.
AB  - OBJECTIVE: To assess follow-up and histologic outcomes by age for an indigent
      urban cohort of women with minimally abnormal cytology. STUDY DESIGN:
      Retrospective analysis of Pap tests was performed (January 2, 2002, to June 30,
      2005). Adolescents (age < 21) and women with atypical squamous cells of
      undetermined significance (ASCUS)/high-risk human papillomavirus (HPV) and low
      grade squamous intraepithelial lesions (LSIL) Pap results were studied and
      followed for outcomes at 2 years. The chi2 test was performed to evaluate
      differences among groups; statistical significance was established as p < or =
      0.05. RESULTS: A total of 2,266 women were studied--676 adolescents, 1,063 women
      aged 21-30 years, and 527 women > 30 years of age. Results included 619 ASCUS/
      high-risk HPV and 1,647 LSIL results. Compliance was similar across age-groups;
      31% never returned for follow-up. CIN2 was detected in 18.8% of adolescents,
      21.6% of women aged 21-30, and 15.7% of women > 30 years (p = 0.53). CIN3 was
      detected in 8.5% of adolescents, 8.1% of women aged 21-30, and 7.7% of women > 30
      years (p = 0.55). CONCLUSION: Adolescents and women had similar rates of loss to
      follow-up after having a minimally abnormal Pap test. The likelihood of detecting
      CIN2-3 was similar regardless of age.

PMID- 20795352
TI  - The effect of the night float rotation on annual in-training examination
      performance.
AB  - OBJECTIVE: To assess whether night-float rotation affected resident performance
      on the Council on Resident Education in Obstetrics and Gynecology (CREOG) in
      service examination. STUDY DESIGN: Review of annual CREOG in-service examination
      scores standardized for postgraduate year level (2001-2009) compared scores for
      residents on night float rotation at time of examination to those on non-night
      float rotation. Data were analyzed by linear mixed effects model. RESULTS: Data
      were obtained for 72 residents, 20 of whom were on night float at time of at
      least one examination. One to four test scores were available for each resident
      (total 225 test scores). Average test score was 213 (SD = 20). The mean score for
      residents on night float was 214 (95% CI 207-221); the mean score for those on
      non-night float rotations was 212 (95% CI 208-216, p = 0.53). Sample size was
      sufficient to detect a difference of 12 points with 80% power. CONCLUSION:
      Although night float rotations necessitate a complete reversal in sleep
      schedules, we found that night float service did not significantly affect scores
      On the annual in-service examination. To our knowledge, no studies have evaluated
      the impact of this schedule on test-taking ability.

PMID- 20795353
TI  - Short interpregnancy interval and misoprostol as additive risks for uterine
      rupture: a case report.
AB  - BACKGROUND: Short interpregnancy interval and uterine instrumentation are risk
      factors for uterine rupture in subsequent pregnancies. Misoprostol as a
      uterotonic agent is an additive risk factor for rupture of a scarred uterus.
      CASE: Misoprostol induction for a term stillbirth was complicated by uterine
      rupture. Risk factors for this uterine rupture might have included interpregnancy
      intervals of < 7 months, prior uterine instrumentation, and misoprostol as a
      uterotonic agent. CONCLUSION: Caution and a high index of suspicion are warranted
      when using misoprostol as a uterotonic agent after a short interpregnancy
      interval.

PMID- 20795354
TI  - Quality of care during off-peak hours: are you monitoring this?

PMID- 20795355
TI  - Improving quality on off-peak hours.

PMID- 20795356
TI  - CMS releases final meaningful use rule.

PMID- 20795357
TI  - Study shows 'troubling results' with CPOE alerts.

PMID- 20795358
TI  - Complying with TJC pain management standards.

PMID- 20795359
TI  - Free radicals: their beneficial and detrimental effects on sperm function.
AB  - Free radicals are molecules with one or more unpaired electron(s) commonly found
      in seminal plasma. Physiologically, free radicals control sperm maturation,
      capacitation and hyperactivation, the acrosome reaction, and sperm-oocyte fusion.
      Pathologically, free radicals induce lipid peroxidation, DNA damage and apoptosis
      of spermatozoa. The present review deals with both the beneficial and detrimental
      effects of free radicals on sperm function.

PMID- 20795360
TI  - A novel DNA vaccine constructed by heat shock protein 70 and melanoma antigen
      encoding gene 3 against tumorigenesis.
AB  - Melanoma antigen-encoding gene 3 (MAGE-3) is an ideal candidate for a tumor
      vaccine although its potency need to be increased. Heat shock proteins (HSPs)
      represents a potential approach for increasing the potency of DNA vaccines. In
      the present study, a fusion DNA vaccine composed of Mycobacterium tuberculosis
      HSP70 and MAGE-3 was constructed and used to immunize C57BL/6 mice against B16 or
      B16-MAGE-3 tumor cells. The results show that the HSP70-MAGE-3 fusion DNA vaccine
      enhanced the frequency of MAGE-3-specific cytotoxic T-cells as compared to the
      MAGE-3 DNA vaccine or the HSP70/MAGE-3 cocktail DNA vaccine (P < 0.05). In
      conclusion, the results indicate that the HSP70-MAGE-3 fusion DNA vaccine can
      strongly activate MAGE-3 specific cellular immunological reactions and thus
      significantly inhibit the growth of B16-MAGE-3 tumors, improving the survival of
      tumor-bearing mice, and the HSP70-MAGE-3 fusion DNA vaccine has a significant
      therapeutic effect on the tumors that express MAGE-3 antigens.

PMID- 20795361
TI  - Noggin induces human bone marrow-derived mesenchymal stem cells to differentiate
      into neural and photoreceptor cells.
AB  - The present study was undertaken to explore the effect of noggin on neuronal
      differentiating potential of human bone marrow-derived mesenchymal stem cells
      (hBMMSCs) in vitro so as to provide a means of alleviate retinal degeneration. A
      green fluorescent protein-tagged noggin gene was transferred into adult hBMMSCs
      or induce hBMMSCs with classical inducer, epidermal growth factor(EGF). Neurons
      were observed as early as 48 h after transduction of hBMMSCs with a noggin
      adenoviral vector. Differentiation peaked by 10 days in culture, and these
      differentiated cells expressed multiple markers including rhodopsin (18.4 +/-
      1.5% of cells), chx10 (4.8 +/- 0.6%), nestin (4.2 +/- 0.8%), and Nrl (3.7 +/-
      0.4%), as verified by immunofluorescence staining. Noggin-transduced cells
      produced more photoreceptor cells than non-transduced cells, suggesting that
      noggin has the ability to induce hBMMSCs to trans-differentiate into
      photoreceptor cells. In contrast, induction with EGF for 10 days led to lower
      levels of rhodopsin and chx10, and undetectable levels of Nrl and Nestin. These
      findings suggested noggin-transduced hBMMSCs produced more photoreceptor cells
      than EGF-induced cells. It is suggested that the present protocol has application
      in cell replacement therapy for patients suffering from photoreceptor cell loss.

PMID- 20795362
TI  - Effect of dihydrotestosterone on gastrointestinal tract of male Alzheimer's
      disease transgenic mice.
AB  - The cause of Alzheimer's disease (AD) is still unknown. While research
      contributions identifying brain as locus of the disease is growing, evidence of
      severely impaired gastrointestinal (GI) functions with ageing too is
      accumulating, there is an equal dearth of information on GI tract in AD
      condition. The aim of this study was to assess the molecular, histological,
      morphological and microflora alterations of GI tract in male Alzheimer's
      transgenic mice. The present study also investigates the effect of
      dihydrotestosterone (DHT) treatment (1 mg/kg) on AD mice. Histoarchitecture data
      revealed a significant decrease in the villi number, muscular layer thickness,
      villi length, width, crypt length, enterocyte length and nuclei length. A shift
      in colon feces microbial community composition was observed by fatty acid methyl
      ester analysis. Amyloid precursor protein (APP) expression levels in intestine
      significantly increased in AD mice revealing its toxicity. DHT treatment
      attenuated the effect caused by AD on GI morphometrics, APP expression and colon
      micro flora population. These results for the first time reveal the quantitative
      and qualitative characteristics of GI tract in male Alzheimer's disease
      transgenic mice.

PMID- 20795363
TI  - Effect of anti-depressants on neuro-behavioural consequences following impact
      accelerated traumatic brain injury in rats.
AB  - Disruption of normal neuronal networks and neurotransmitters like serotonin and
      norepinephrine levels in post traumatic brain injury (TBI) are observed to be the
      primary causative agent for depression/anxiety. This communication reports the
      efficacy of various classes' anti-depressants in the treatment of
      depression/anxiety following TBI in rats. Chronic treatment with anti-depressants
      (escitalopram and venlafaxine) leads to improvement in the depressive/anxiogenic
      like behaviour in the TBI rat and corroborates the notion of the involvement of
      serotonin and norepinephrine in the behavioural consequences of post-TBI. Chronic
      treatments with escitalopram and venlafaxine significantly reversed the effect of
      TBI as compared to vehicle-treated TBI group. The results showed a quantitative
      battery of neuro-behavioural functional assessments that correlates with neuronal
      damage following traumatic brain injury.

PMID- 20795364
TI  - Hydroalcoholic extract of Emblica officinalis Gaertn. affords protection against
      PTZ-induced seizures, oxidative stress and cognitive impairment in rats.
AB  - The cognitive impairment seen in epileptics may be a consequence of either the
      underlying epileptogenic process alone or it could manifest on account of the use
      of antiepileptic drugs that cause cognitive impairment as an adverse effect or
      both. Thus, there is a need for drugs that can suppress epileptogenesis without
      contributing to or, if possible, by acting to prevent the development of
      cognitive impairment. Emblica officinalis, an Indian medicinal plant, has marked
      antioxidant property. The effect of seven days pretreatment of 300, 500 and 700
      mg/kg doses of hydroalcoholic extract of E. officinalis (HAEEO) administered
      intraperitoneally to rats was evaluated on pentylenetetrazole (PTZ) induced
      seizures, cognitive deficit and oxidative stress markers viz malondialdehyde
      (MDA) and glutathione. The 500 and 700 mg/kg ip doses of HAEEO completely
      abolished the generalized tonic seizures and also improved the retention latency
      in passive avoidance task. Further, HAEEO dose-dependently ameliorated the
      oxidative stress induced by PTZ. These findings suggest the potential of HAEEO to
      be used as an adjuvant to treatment with antiepileptic drugs.

PMID- 20795365
TI  - Effect of Convolvulus pluricaulis Choisy and Asparagus racemosus Willd on
      learning and memory in young and old mice: a comparative evaluation.
AB  - A dose dependent enhancement of memory was observed with A. racemosus and C.
      pluricaulis treatment as compared to control group when tested on second day. A.
      racemosus and C. pluricaulis at the dose of 200 mg/kg, po showed significantly
      higher percent retentions, than piracetam. Multiple treatment with A. racemosus
      and C. pluricaulis for three days also demonstrated significant dose dependent
      increase in percent retentions as compared to control group. The effect was more
      prominent with C. pluricaulis as compared with piracetam and A. racemosus. A
      significantly lower percent retention in aged mice was observed as compared to
      young mice. Aged mice (18-20 months) showed higher transfer latency (TL) values
      on first and second day (after 24 h) as compared to young mice, indicating
      impairment in learning and memory. Pretreatment with A. racemosus and C.
      pluricaulis for 7 days enhanced memory in aged mice, as significant increase in
      percent retention was observed. Significantly higher retention was observed with
      C. pluricaulis (200 mg/kg; po) as compared with piracetam (10 mg/kg/; po). Post
      trial administration of C. pluricaulis and A. racemosus extract demonstrated
      significant decrease in latency time during retention trials. Hippocampal regions
      associated with the learning and memory functions showed dose dependent increase
      in AChE activity in CA 1 with A. reacemosus and CA3 area with C. pluracaulis
      treatment. The underlying mechanism of these actions of A. racemosus and C.
      pluricaulis may be attributed to their antioxidant, neuroprotective and
      cholinergic properties.

PMID- 20795366
TI  - Cysteine-rich cyanopeptide beta2 from Spirulina fusiformis exhibits plasmid DNA
      pBR322 scission prevention and cellular antioxidant activity.
AB  - Isolation of three different active peptides from C-phycocyanin (C-pc) beta chain
      of S. fusiformis and their biological properties are reported. Phycocyanin
      peptide beta fraction 2 (cyanopeptide beta 2) facilitated both antioxidant and
      plasmid DNA strand scission prevention activity due to higher cysteine moieties
      in the isolated peptide. The peptide significantly scavenged the free radicals
      like 1-1,-diphenyl-2-picryl hydrazyl and ferric reducing ability of plasma,
      increased the absorbance values in reducing power and also showed the higher
      trolox equivalent antioxidant capacity values in total reactive antioxidant
      potentials assay. Cyanopeptide beta 2 also inhibited reactive oxygen species
      induced DNA pBR322 damage in dose dependent manner along with free radical
      scavenging properties suggesting the role in the DNA integrity which is also
      evident by DNA binding activity of peptide. In addition, the generation of
      reactive oxygen species (ROS) was dose dependent (10 and 20 ng/ml) and
      significantly quenched by cyanopeptide beta2 in human fibroblast cell line TIG 3
      20. In vitro cell scratch injury assay demonstrated the capacity of cyanopeptide
      beta2 in cell migration in to wounded area suggesting fibroblast proliferation
      and migration. The results suggest that cyanopeptide beta2 can be a free radical
      scavenger and effective peptide for future biomedical applications like wound
      healing, atherosclerosis, cell redox potential and hypoxia.

PMID- 20795367
TI  - Anti-allergic, anti-inflammatory and anti-lipidperoxidant effects of Cassia
      occidentalis Linn.
AB  - Cassia occidentalis Linn. mast cell degranulation at a dose of 250 mg/kg, showed
      dose dependent stabilizing activity towards human RBC, with is widely used in
      traditional medicine of India to treat a number of clinical conditions including
      allergy and inflammatory manifestations. In the present study anti-allergic, anti
      inflammatory and anti-oxidant properties of C. occidentalis whole plant ethanolic
      extract (CO) was investigated. Effects of CO on rat mast cell degranulation
      inhibition and human red blood cell (HRBC) membrane stabilization were studied in
      vitro following standard methods. The anti lipidperoxidant effects of CO were
      also studied in vitro. Effect of CO on carrageenan-induced mouse paw oedema
      inhibition was also assessed. CO significantly decreased maximum protection of
      80.8% at 15 microg/ml. The extract also caused significant reduction in
      malondialdehyde (MDA) levels of murine hepatic microsomes at 100 microg/ml (56%)
      and significantly reduced carrageenan induced inflammation in mice at a dose of
      250 mg/kg. Results of the present study indicated that CO inhibited mast cell
      degranulation, stabilized HRBC membrane thereby alleviating immediate
      hypersensitivity besides showing anti oxidant activity.

PMID- 20795368
TI  - Effect of Cyclea peltata Lam. roots aqueous extract on glucose levels, lipid
      profile, insulin, TNF-alpha and skeletal muscle glycogen in type 2 diabetic rats.
AB  - In view of multi-dimensional activity of plant drugs beneficial to complex
      disorders like diabetes, the present study has been undertaken to evaluate the
      effect of aqueous extract of C. peltata roots on serum glucose, lipid profile,
      insulin, inflammatory marker namely tumour necrosis factor (TNF)-alpha and muscle
      glycogen in type 2 diabetic rats. Aqueous extract of C. peltata at 40 and 60
      mg/kg dose significantly decreased both the fasting and postprandial blood
      glucose of type 2 diabetic rats; 60 mg/kg dose having more pronounced effect on
      hyperglycemia. An enhanced insulin levels by the aqueous extract is primary for
      its glucose and lipid lowering activity. The extract significantly decreased the
      elevated TNF-alpha in type 2 diabetic rats. The extract at 40 and 60 mg/kg dose
      increased the glycogen levels in skeletal muscle by 58 and 60% respectively.
      Improved glycogen in peripheral tissue such as skeletal muscle indicates the
      ability of plant drug to combat insulin resistance of type 2 diabetes.

PMID- 20795369
TI  - Effect of carnitine supplementation on mitochondrial enzymes in liver and
      skeletal muscle of rat after dietary lipid manipulation and physical activity.
AB  - Effect of carnitine supplementation in enhancing fat utilization was investigated
      by looking into its effects on mitochondrial respiratory enzymes activity in
      liver and muscle as well as on membrane fatty acid profile in rats fed with
      hydrogenated fat (HF) and MUFA-rich peanut oil (PO) with or without exercise.
      Male Wistar rats were fed HF-diet (4 groups, 8 rats in each group) or PO-diet (4
      groups, 8 rats in each group), with or without carnitine for 24 weeks. One group
      for each diet acted as sedentary control while the other groups were allowed
      swimming for 1 hr a day, 6 days/week, for 24 weeks. The PO diet as well as
      exercise increased the activities of mitochondrial enzymes, NADH dehydrogenase,
      NADH oxidase, cytochrome C reductase, cytochrome oxidase, while carnitine
      supplementation further augmented the oxidative capacity of both liver and muscle
      significantly by enhancing the activity of carnitine palmitoyl transferase and
      the respiratory chain enzymes. These effects can be attributed to the enhanced
      unsaturated fatty acids in phospholipids of mitochondria and may be due to
      increased fluidity of the membrane in these rats. Results of this study show a
      significant health promoting effects of carnitine supplementation which could be
      further augmented by regular exercise.

PMID- 20795370
TI  - Racial divergence of a rare laboratory-evolved centromeric fission Cytorace of
      nasuta-albomicans complex of Drosophila.
AB  - Fissioncytorace-1, a member of the nasuta-albomicans complex of Drosophila is an
      evolutionary product of centric fission, which had occurred in the chromosome X3
      of Cytorace 1, a hydridization product of Drosophila nasuta nasuta male (2n=8)
      and Drosophila nasuta albomicans female (2n=6). Cytorace 1 (males 2n=7; females
      2n=6) has inherited this chromosome from its D. n. albomicans parent. The
      chromosome X3 of D. n. albomicans is a derivative of a centric fusion between the
      acrocentric chromosome 3 and the chromosome X of D. n. nasuta. The
      Fissioncytorace-1 has crossed 200 generations from the time of its evolution in
      the laboratory environment. When this centromeric fission race was subjected to
      some of the morphophenotypic and fitness assessment to find its overall
      population fitness showed, increased body size, sternopleural bristle, ovarioles,
      lifetime fecundity and fertility with reduced interspecific competitive ability
      and hatching success when compared with its parent (Cytorace 1). These results
      suggest that the hybrid races must have encountered an early event of
      recombinational raciation during their evolution in the laboratory environment,
      which is a unique observation in animal system illustrating the increase in the
      tempo of evolution after the event of hybridization.

PMID- 20795371
TI  - Enhancement of magnetotactic bacterial yield in a modified MSGM medium without
      alteration of magnetosomes properties.
AB  - Magnetotactic bacteria (MTB), Magnetospirillum magnetotacticum (MS-1) were
      successfully grown in modified magnetic spirillum growth medium (MSGM) at normal
      laboratory environment. About five-time increase in the bacterial yield was
      achieved in the modified MSGM medium without compromising their magnetosomes
      properties. Transmission electron and scanning electron microscopy (TEM & SEM)
      were used for morphological study of MTB. Energy dispersive analysis of X-rays
      (EDAX) and vibrating sample magnetometer (VSM) techniques, respectively, were
      used to elucidate the phase and magnetization in the bacterially synthesized
      magnetosomes. These studies were important to cross-check the morphology of
      magnetosomes, as the formation of magnetosomes was highly sensitive to
      environmental conditions.

PMID- 20795372
TI  - Protecting the hearing of performing artists.

PMID- 20795373
TI  - Focal dystonia in musicians: phenomenology, pathophysiology, triggering factors,
      and treatment.
AB  - Musician's dystonia is a task-specific movement disorder that manifests itself as
      a loss of voluntary motor control in extensively trained movements. Approximately
      1% of all professional musicians develop musician's dystonia, and in many cases,
      the disorder terminates the careers of affected musicians. The pathophysiology of
      the disorder is not completely clarified. Findings include 1) reduced inhibition
      at different levels of the central nervous system, 2) maladaptive plasticity and
      altered sensory perception, and 3) alterations in sensorimotor integration.
      Epidemiological data demonstrate a higher risk for those musicians who play
      instruments requiring maximal fine-motor skills. For instruments where workload
      differs across hands, focal dystonia appears more often in the more intensely
      used hand. In psychological studies, musicians with dystonia have more anxiety
      and perfectionist tendencies than healthy musicians. These findings strengthen
      the assumption that behavioral factors may be involved in the etiology of
      musician's dystonia. Preliminary findings also suggest a genetic contribution to
      focal task-specific dystonia with phenotypic variations including musician's
      dystonia. Treatment options include pharmacological interventions, such as
      trihexyphenidyl or botulinum toxin-A, as well as retraining programs and
      ergonomic changes in the instrument. Patient-tailored treatment strategies may
      significantly improve the situation of musicians with focal dystonia. Positive
      results after retraining and unmonitored technical exercises underline the
      benefit of an active involvement of patients in the treatment process. Only a
      minority of musicians, however, return to normal motor control using the
      currently available therapies.

PMID- 20795374
TI  - Self-reported and reported injury patterns in contemporary dance students.
AB  - BACKGROUND: Injury is a major concern among dancers, as currently rates are
      reported as being high. The purpose of the present study was to assess the
      incidence and details of injuries across an academic year at a full-time
      contemporary dance school. METHODS: A questionnaire was distributed to 57 dancers
      at the end of their first academic year. Reported injury information was also
      retrieved from a database as collected from a physiotherapist over the same
      period. RESULTS: Differences were found between the reported and self-reported
      information, particularly with reference to shin injuries. The majority of
      injuries occurred in November and May, noted to be close to assessment periods.
      CONCLUSION: Injury rates in contemporary dance are high; notably, 89% of dancers
      reported one or more injuries. This problem is particularly evident in the lower
      limb. Med Probl Perform Art 2010; 25:10-15.

PMID- 20795375
TI  - Cardiac response during trumpet playing.
AB  - Heart rate, heart rate variability, stroke volume, and cardiac output were
      measured while six college students and six professionals played trumpet. One
      minute rest periods were followed by 1 minute of playing exercises designed to
      assess the effects of pitch and articulation. Heart rate and heart rate
      variability increased during playing, but stroke volume decreased. Changes in
      heart rate between resting and playing were greater for students, although beat
      to-beat variability was larger for professionals in the upper register. These
      results suggest that expertise is characterized by greater physiological
      efficiency.

PMID- 20795376
TI  - The influence of profession on functional ankle stability in musicians.
AB  - OBJECTIVE: The aim of this study was to examine the influence of extensive work
      related use of the feet on functional ankle stability among musicians. METHODS:
      Thirty professional organists were compared to professional pianists and
      controls. All participants completed a questionnaire. Range of motion (ROM),
      peroneal reaction time, and positional sense tests of the ankle were measured.
      The postural balance control was investigated with the Biodex Stability System
      for the stable level 8 and unstable level 2. Statistical analysis was done with
      the Kruskal-Wallis test, Mann-Whitney test with Bonferroni-Holm correction, and
      Fisher's exact test. RESULTS: Nine of 30 organists compared to 5 of 30 pianists
      and controls reported ankle sprains in their medical history. Pianists had a
      significant increased flexion of both ankle joints compared to organists (p <
      0.01) and increased flexion of the right ankle joint compared to controls (p =
      0.02). The positional sense test and postural balance control showed no
      significant differences among groups. The peroneal reaction time of the right
      peroneus longus muscle was significantly increased in pianists compared to
      controls (p = 0.008). CONCLUSIONS: Organists have shown a high incidence of ankle
      sprains. Despite their extensive work-related use of the ankle joints, organists
      have neither increased functional ankle stability nor increased ROM of their
      ankle joints in comparison to controls. Pianists have increased flexion of the
      ankle joint, perhaps due to the exclusive motion of extension and flexion while
      using the pedals. To minimize injuries of the ankle and improve functional ankle
      stability as well as balance control, proprioceptive exercises of the ankle in
      daily training programs are recommended.

PMID- 20795377
TI  - Measurement and prediction of sound exposure levels by university wind bands.
AB  - The purpose of this study was to determine sound exposure levels generated in two
      college wind bands. Dosimeter data from a large sample of ensemble-based
      instructional activities (n = 43) was collected over time and processed to assess
      associations with predictor variables that may be relevant to this context,
      including indicators of time spend at various intensity levels, maximum and peak
      sound levels, degree of variability of sound levels over time, and the percentage
      of time playing music. The mean dose per event for the entire sample was 109.5%
      and ranged from 53.8% to 166.9%. Results of linear regression analysis revealed
      that regressors accounted for a significant proportion of the variance in dose (F
      = 128.42, p < 0.000) and a statistically significant and very large (96% variance
      accounted for) contribution to the prediction of dose. Findings implicate the
      critical role of the instructor and teaching pedagogy.

PMID- 20795378
TI  - The overused airway: lessons from a young trumpet player.
AB  - Young trumpet players are predisposed to certain performance-related health
      risks. Nevertheless, the published experience with specific disorders is
      considered confusing and anecdotal. In the context of a review of the literature,
      we analyze a case report of a young patient who presented with two different
      disorders typically related to trumpet playing. After considering the diagnoses
      that had been made elsewhere, we were able to make the correct diagnoses and
      choose the correct treatment. We conclude that physicians need to be aware of
      these disorders, because they could be mistakenly attributed to instrumental
      performance itself or misinterpreted as serious conditions that require medical
      intervention.

PMID- 20795379
TI  - A prisoner's dilemma with asymmetrical payoffs: revealing the challenges faced by
      performing arts health and wellness practitioners.
AB  - In a prisoner's dilemma, constructed narratives are used to demonstrate problems
      within individual rationality and decision-making. Performing artists can be seen
      as facing a type of prisoner's dilemma in their careers: they must practice
      repeated movements for long periods in order to improve, yet despite the short
      term perception of gained artistic benefit, the long-term consequences may be
      playing-related musculoskeletal disorders and injury. To help avoid such an
      outcome, educators and health and wellness practitioners must function as
      negotiators, engaging in discussions of artistry as part of establishing
      credibility and encouraging behaviors that keep artists in efficient, healthy
      behaviors. By setting practice time limits that are considerate of the intensity
      of each specific task, performers can improve their performance on a daily basis
      and become more skilled at planning their future training.

PMID- 20795380
TI  - [Genetic characteristics of Haemophilus influenzae type b isolated from children
      with bacterial meningitis in Moscow in 2007-2009].
AB  - AIM: Genetic characterization of 37 strains and CSF samples containing DNA of
      Haemophilus influenzae type b isolated in Moscow during 2007-2009. MATERIALS AND
      METHODS: Multilocus sequence-typing method was used and also variant of method
      for capsule type determination was approbated. RESULTS: Ten sequence types, of
      which 7 were described in previous studies and 3 were revealed for the first time
      during this work, were detected in studied sample. ST-6 and ST-92 were the most
      frequently detected--9 strains (24%) of Hib belonging to each sequence type were
      revealed. All detected sequence types, except one, belong to clonal complex "ST
      6" ("A1/A2"). Obtained data were compared with results of typing of Hib strains
      isolated in Moscow in 1999-2001. Genetic changes in studied population of Hib are
      characterized by decreased proportion of Hib belonging to ST-6 (from 54% to 24%)
      and increased number of sequence types belonging to clonal complex "ST-6"
      differing from ST-6 on more than one locus of allelic profile (from 2 types [2
      strains, 5.4%] to 5 types [9 strains, 24%]). CONCLUSION: In 2007-2009, number of
      Hib strains with sequence type ST-95 (7 strains, 19%), which is typical for
      strains circulating in Russia, is markedly increased. Capsule type I was detected
      in 32 (86.5%) of studied strains, whereas capsule type II--in 5 (13.5%) of
      studied strains. Capsule type II was detected only in Hib strains with ST-80
      sequence type.

PMID- 20795381
TI  - [Actual problems of infectious diseases prevention at present time].

PMID- 20795383
TI  - [Therapeutic bacterial vaccine Immunovac in complex treatment of patients with
      chronic pyoderma].
AB  - AIM: Assessment of therapeutic effect and immunologic parameters during use of
      Immunovac vaccine for complex treatment of chronic forms of pyoderma. MATERIALS
      AND METHODS: Ninety-five patients with different clinical forms of chronic
      pyoderma (furunculosis, hydradenitis, chronic ulcerative and ulcerative-vegetans
      pyoderma, folliculitis, impetigo etc.) were studied. Fifty-nine patients received
      immunotherapy with Immunovac vaccine together with basic therapy and 36 patients
      comprised control group treated only with basic therapy. Studied immunologic
      parameters were as follows: assessment of functional activity of lymphocytes,
      determination of lymphocyte subpopulations by flow cytometry, total
      immunoglobulins classes A, G, M by radial immunoduffusion, affinity of antibodies
      by enzyme immunoassay, levels of IFNalpha and IFNgamma. RESULTS: Use of Immunovac
      vaccine in complex treatment of patients with chronic forms of pyoderma enhanced
      clinical effect of basic therapy, which expressed in decrease of severity and
      frequency of disease relapses irrespective to clinical form and severity of
      pyoderma. Therapeutic effect during use of Immunovac vaccine amounted 84.7%,
      whereas in control group it was 41.6% after 12 months of follow-up. Increase of
      functional activity of neutrophils, subpopulation of lymphocytes with markers
      CD4+, CD8+, CD72+, affinity of antibodies as well as induced production of
      IFNalpha and IFNgamma was revealed. Correction of immunologic parameters
      correlated with positive results of patients treatment. CONCLUSION: Inclusion of
      bacterial polycomponent vaccine Immunovac in complex treatment of patients with
      chronic pyoderma promotes enhancement of therapeutic effect of basic therapy and
      correction of immunologic parameters.

PMID- 20795382
TI  - [Immunization of patients with chronic obstructive pulmonary disease with
      vaccines of Bubo-M and hepatitis B].
AB  - AIM: To assess tolerability and immunological activity of Bubo-M vaccine and
      hepatitis B vaccine in patients with chronic obstructive pulmonary disease
      (COPD). MATERIALS AND METHODS: Sixty-three patients with moderate and severe COPD
      aged 35-65 years were immunized against diphtheria, tetanus, and hepatitis B.
      Bubo-M vaccine as well as vaccine against hepatitis B were used for immunization.
      Immunologic effect of vaccination was assessed by measurement of serum antibody
      level to HBsAg as well as to diphtheria and tetanus toxoids. Assessment of
      antibody level to HBsAg was performed by ELISA, and levels of antibodies to
      diphtheria and tetanus toxoids--by micromethod in direct hemagglutination assay.
      Reactogenicity of Bubo-M vaccine was measured according to duration and intensity
      of local and systemic reactions. RESULTS: The local and systemic reactions were
      infrequent, serious adverse events after vaccination were not observed. Six
      months after vaccination, protective antibody titers to hepatitis B, diphtheria
      and tetanus were determined in all immunized persons--either healthy, or with
      COPD. During completion of vaccination schedule, significant reduction of acute
      respiratory infections rate and main disease exacerbations was noted in patients
      with COPD. CONCLUSION: Good tolerability and high immunogenicity of Bubo-M and
      hepatitis B vaccines were demonstrated in both groups of vacinees. These vaccines
      could be recommended for booster vaccination of adults with COPD.

PMID- 20795384
TI  - [Specific antibodies in children with recurrent respiratory infections immunized
      with pneumo 23 and Act-HIB vaccines].
AB  - AIM: Assessment of specific IgG levels in children with recurrent respiratory
      infections after immunization with Pneumo 23 and Act-HIB vaccines. MATERIALS AND
      METHODS: Concentrations of IgG to polysaccharide capsular antigens and cell wall
      antigens of Streptococcus pneumoniae and Haemophilus influenzae were measured by
      solid-phase ELISA in sera of 256 immunized children. RESULTS: Increase of levels
      of IgG to cell wall antigens and certain polysaccharide antigens was observed in
      patients with low or intermediate antibody levels at baseline. CONCLUSION:
      Obtained results allow to conclude that vaccination of children with recurrent
      respiratory and middle ear infections results in induction of IgG production that
      proves immunological effect of performed vaccination.

PMID- 20795385
TI  - [Effect of pneumo 23 vaccine administration in patients with chronic obstructive
      pulmonary disease of intermediate severity].
AB  - AIM: To study dynamics ofclinico-immunological parameters in patients with
      chronic obstructive pulmonary disease (COPD) of intermediate severity after
      administration of Pbeumo 23 vaccine. MATERIALS AND METHODS: Forty-five patients
      with COPD of intermediate severity comparable to sex, age, duration of smoking
      and COPD history were divided on two groups: main group (I)--20 patients
      vaccinated with Pneumo 23 vaccine, and control group (II)--25 patients, which
      received only standard treatment. Complete blood count, sputum cytology,
      expiratory function as well as immunological parameters (levels of CD4+, CD8+,
      CD20+, CD25+, and IFN-gamma) were studied at baseline as well as 21 days, 3
      months, and 6 months after vaccination. RESULTS: Stable remission of the disease
      (during 6 months) was noted in all patients in group I and in 20% of patients in
      group II. In group I, levels of CD4+ and CD8+ lymphocytes did not change
      significantly, whereas number of activated T-lymphocytes (CD25+) significantly
      increased. There were substantial increase of IFN-gamma level and decrease of IgE
      level in serum in group I that could point to predominance of Thl-dependent
      immune response and activation of cellular immunity. There were no such changes
      in group II. CONCLUSION: Administration of Pneumo 23 resulted in decrease of
      intensity of local inflammation and prolonged remission of COPD that allowed to
      recommend inclusion of vaccination to standard protocols of treatment for such
      patients.

PMID- 20795386
TI  - [Induction of dendritic cells maturation by staphylococcal antigens].
AB  - AIM: To study the ability to induce dendritic cells maturation obtained from bone
      marrow of mice by staphylococcal complex of antigens containing bacterial ligands
      for Toll-like receptors (lipopeptides, lipoproteins, and peptidoglycans).
      MATERIALS AND METHODS: Commercially available TNF-alpha, inductors ofdendritic
      cells (DCs) maturation, as well C57/BL line mice were used for the study.
      Immunophenotype of DCs was assessed by flow cytometry and monoclonal antibodies
      against cellular antigens. Cytological study using phase-contrast microscopy as
      well as electron microscopy were performed. Levels of cytokines were measured by
      ELISA. RESULTS: Obtained DCs had typical morphologic characteristics of mature
      cells. However the culture was still heterogenous with presence of macrophages
      that was evident from immunophenotype of obtained cells: CD34(-/+), CD38+, CD40+,
      CD80+, CD86+, MHC II+, F4/80(-/+). Number of TLR2-expressing cells was also
      reliably increased in culture of DCs that confirms the presence of corresponding
      ligands binding with this type of receptor in the preparation. Application of
      each studied preparation resulted in synthesis of large amount of TNF-alpha, IL
      6, IL-1beta, IL-12 by DCs, and IFN-gamma by several types of them (RP and CB24).
      Although the intensity of induced cytokine synthesis varied for each preparation,
      it was many times higher compared with immature DCs. CONCLUSION: High synthesis
      level and wide spectrum of cytokine production demonstrated that under the
      influence of bacterial ligands DCs acquired characteristics needed for effective
      antigen presentation and priming of immune response.

PMID- 20795387
TI  - [Monoclonal antibodies against human secretory component: epitope specificity and
      utility for immunoanalysis].
AB  - AIM: To develop and characterize by immunochemical methods the panel of
      monoclonal antibodies (MAbs) recognizing different antigenic determinants ofhuman
      secretory component (SC) molecule. MATERIALS AND METHODS: sIgA and SC were
      obtained from colostrum by combination of ion-exchange chromatography and gel
      filtration. Recombinant SC was expressed in Escherichia coli cells transformed by
      construction that contained fragment of gene coding extracellular domain of
      receptor for polymeric Ig. MAbs were produced and studied using hybridoma
      technologies and different methods of immunoenzyme analysis respectively.
      RESULTS: Panel comprising 10 MAbs against human SC of which 4 types of antibodies
      recognize cryptic epitopes of free SC and other 6 types recognize epitopes
      exposed both on SC and sIgA. MAbs panel contains antibodies interacting with
      conformational and linear epitopes of antigen. Three from obtained MAbs bind to
      SC epitopes which structure is determined by presence of carbohydrate residues in
      the molecule of antigen. Immunometric systems were developed which allow to
      differentially detect free SC and sIgA. CONCLUSION: Developed and characterized
      MAbs panel recognizing different epitopes of SC molecule opens new opportunities
      for laboratory and basic research of human secretory immunity.

PMID- 20795388
TI  - [State of antiendotoxin defense during community-acquired pneumonia].
AB  - AIM: To assess the effect of systemic endotoxinemia and LPS-induced immune
      response on severity of community-acquired pneumonia (CAP). MATERIALS AND
      METHODS: Clinico-immunological follow-up of 60 patients with CAP of different
      severity was conducted. LPS was quantitatively measured by ENDOSAFE ENDOCHROME
      (0.015-0.12 EU/ml), LBP--by Hbt Human LBP ELISA (min 1 ng/ml), IgG to core region
      of LPS--by Hbt EndoCAb ELISA (min 0.125 MU/ml) ("HyCult biotechnology",
      Netherlands). RESULTS: Level of LPS in blood was not increased, whereas there was
      increase of antiendotoxin proteins in patients with more severe CAP with Gram
      negative or mixed bacterial flora identified. Correlation between levels of LBP,
      IgG to core-region of LPS, IL-6, TNF-alpha, IL-4 and immune response
      abnormalities during severe forms of disease was demonstrated. CONCLUSION: State
      of antiendotoxin immunity is an etiologic marker of CAP and its severity.

PMID- 20795390
TI  - [Influence of low frequency magnetic field on characteristic of Pseudomonas
      aeruginosa].
AB  - AIM: To assess the level of bacteriostatic effect of low frequency magnetic field
      (LFMF) on Gram-negative bacteria able to form biofilms (Pseudomonas aeruginosa)
      compared to able to aggregation oligotrophes Caulobactor crescentus, Arcicella
      aquatica and Verrucomicrobium spinosum. MATERIALS AND METHODS: Frequencies 0.001
      100 Hz with magnetic induction value 450 mcT1 together with various variants of
      time, duration and conditions of cultivation of bacteria were used.
      Bacteriostatic effectwas assessed by optic methods. RESULTS: Decrease of
      bacterial growth activity with efficacy coefficient Keef = 0.79 +/- 0.03 was
      demonstrated. CONCLUSION: LFMF moderately decreases growth of tested bacterial
      species.

PMID- 20795389
TI  - [Comparison of efficacy of tests for differentiation of typical and atypical
      strains of Yersinia pestis and Yersinia pseudotuberculosis].
AB  - AIM: To characterize species specificity of officially recommended tests for
      differentiation of Yersiniapestis and Yersinia pseudotuberculosis and propose
      additional tests allowing for more accurate identification. MATERIALS AND
      METHODS: Natural, laboratory and typical strains oftwo Yersinia species were
      studied using microbiological, molecular and biochemical methods. For PCR species
      specific primers complementary to certain fragments of chromosomal DNA of each
      species as well as to several plasmid genes of Y. pestis were used. RESULTS: It
      was shown that such attributes of Y. pestis as form of colonies, fermentation
      ofrhamnose, melibiose and urea, susceptibility to diagnostic phages, nutritional
      requirements could be lost in pestis bacterial species or detected in
      pseudotuberculosis species. Such attribute as mobility as well as positive result
      of CoA-reaction on fraction V antigen are more reliable. CONCLUSION: Guaranteed
      differentiation of typical and changed according to differential tests strains is
      provided only by PCR-analysis with primers vlml2for/ISrev216 and JS respectively,
      which are homologous to certain chromosome fragments of one of two Yersinia
      species.

PMID- 20795391
TI  - [Rate of identification and characteristic of Streptococcus pneumoniae isolated
      from carriers and ill children in Khabarovsk region].
AB  - AIM: To assess the role of nasopharyngeal and clinical strains of Streptococcus
      pneumoniae in respiratory disease of children. MATERIALS AND METHODS: Two hundred
      and fifty-eight children attending and not-attending daycare as well as 1292
      children with respiratory diseases admitted to clinic of Research Institute of
      Maternity and Childcare during 2001-2009 were studied. Materials for study were
      pharyngeal swabs and sputum. Identification was performed using optochin disks
      (bioMerieux), latex-agglutination (Slidex meningo-kit, bioMerieux) and
      agglutination on the glass. Fragment of S. pneumoniae genome was determined by
      PCR using diagnostic kits GenePac Spn (IsoGen Ltd., Moscow). RESULTS: Level of
      nasopharyngeal carriage of pneumococci is increased in children with recurrent
      respiratory illnesses as well as in children closed communities of children.
      Strains isolated from nasopharynx were typical on morphological and tinctorial
      characteristics and have increased level of resistance to macrolides and
      decreased level of resistance to penicillin compared to clinical strains of which
      15-20% were optochin-resistant. CONCLUSION: Local serological spectrum of
      pneumococci circulating in Khabarovsk region was determined, which includes 13
      serovariants with predominance of serotypes K1, K19, K6.

PMID- 20795392
TI  - [Immunobiological features of bacterial cells of medical biofilms].
AB  - Biofilm is a integrated multucellular organism with own cycle of development,
      cooperative behavior of units forming it, which coordinated by QS-system based on
      production of signal molecules or autoinductors and ability of bacteria to
      receive these signals. Presence ofbacteria attached to surface of biomedical
      devices and formation of bacterial biofilms in the microorganism could lead to
      chronic inflammation, which characterized by presence of macrophages and
      lymphocytes in the focus of inflammation as well as proliferation of connective
      tissue, accumulation of matrix proteins and stimulation ofangiogenesis. Process
      of biofilm formation associated with activation of QS-system of different agents
      including potentially dangerous bacteria plays certain role in exacerbation of
      gastric and duodenal ulcer diseases, Crohn's disease, myocarditis, asthma,
      diabetes mellitus, cardiovascular and other somatic diseases. Detachment of
      biofilm could lead to enter ofbac-teria in bloodsream and vascular embolism.
      Issues related to ability of bacteria of biofilms to modulate immune response and
      potential for the emerging response to influence the biofilm growth and level of
      expression of bacterial virulence are discussed. Modem views on mechanisms of
      interaction of bacteria of exopolysaccharide biofilm with host's immune response
      factors are reviewed. The most perspective ways to control for biofilm formation
      and their disruption using newly developing drugs are outlined.

PMID- 20795393
TI  - [Swine-origin influenza H1N1/California--passions and facts].
AB  - Analysis of pandemic caused by swine influenza virus H1N1/California showed
      moderate virulence of this virus compared to pandemic viruses, which caused
      pandemics in 1918, 1957, and 1968. During seasonal influenza epidemic in
      countries of southern hemisphere (June-August 2009) despite on circulation of
      H1N1/California strain, epidemics was caused by human influenza viruses H3N2 and
      H1N1. It was concluded that strain H1N1/California could not be attributed to
      pandemic strains of influenza viruses.

PMID- 20795394
TI  - [Secreted proteins of Staphylococcus aureus].
AB  - Modern views on secreted proteins of Staphylococcus aureus are analyzed in the
      review. Spread of this pathogen is partially explained by wide spectrum of
      proteins secreted by this microorganism. Four groups of proteins secreted by
      staphylococci could be assigned. These are peptidoglycanhydrolases, intracellular
      enzymes (proreases, lipases etc.), membrane toxins (hemolyzins and leukocidins),
      and superantigens. Role of some proteins, especially belonging to latter groups,
      for the staphylococcal virulence and pathogenesis of staphylococcal infectious is
      known at this time. Genome sequencing of several strains of S. aureus also
      allowed to predict main characteristics of many secreted proteins such as
      molecular mass and spatial structure. Further studies of these proteins could be
      useful for development of staphylococcal vaccines and other immunity-modifying
      drugs.

PMID- 20795395
TI  - [Potentialities of non-invasive diagnosis of liver cirrhosis in children with the
      use of serological markers].
AB  - The study included 95 children with chronic hepatic disorders of different
      etiology. All of them underwent hepatic puncture biopsy for morphological studies
      and calculation of histological sclerosis index based on the Knoddel scale.
      Commercial enzyme immunoassay kits were used to measure hyaluronic acid (HA),
      type IV collagen (CIV), matrix metalloproteinase-1 (MMP-2), transforming growth
      factor-beta 1 (TGF), and leptin levels as non-invasive markers of fibrosis. It
      was shown that concentrations of TGF and MMP-2 at early stages of hepatic
      fibrosis, HA and CIV at its later stages are of diagnostic value.

PMID- 20795396
TI  - [Colonization resistance and immunological reactivity of children's oropharyngeal
      mucosa in health and bronchopulmonary pathology].
AB  - The study group was comprised of 27 practically healthy children, 51 patients
      with acute bronchitis, 15 with chronic bronchitis and 11 with pneumonia. It was
      shown that changes of microbiocoenosis in back of the throat (BOT) were related
      to increased mucosal contamination with normal microflora and opportunistic
      microorganisms. The highest degree of contamination was observed in children with
      acute bronchitis. Normocoenosis was detected only in 13 practically healthy
      children. The disorders of microbiocoenosis took the form of disbiosis and acute
      inflammatory processes in patients with acute and chronic bronchitis and
      pneumonia. However, the large amount of normal flora together with the high Ig
      level ensured marked colonization resistance as evidenced by the values of
      natural colonization coefficient of nasopharyngeal epithelium (NCCNE) and balance
      coefficient (BC). These data suggested development of compensated secondary
      immunodeficiencies. In patients with acute bronchitis and pneumonia, local
      synthesis of Ig prevailed. It is shown that BC can be used to screen children for
      disorders of mucosal immunity. The presence of increased saliva IgE levels in
      patients with acute and chronic bronchitis supports the generally accepted
      concept of bronchi as a "shock organ" in allergic condition. It was demonstrated
      that IgE levels in saliva increase earlier than in serum and may be used as a
      prognostic criterion in patients with bronchopulmonary pathology.

PMID- 20795397
TI  - [Proliferative and mucin-producing activities in the foci of intestinal
      metaplasia associated with chronic atrophic gastritis and gastric ulcer].
AB  - Immunohistochemical studies revealed the dependence of cell regeneration
      parameters at sites of intestinal metaplasia (IM) in gastric mucosa (GM) on the
      character of the background events, such as atrophy and erosive-ulcerative
      defect. Mucin profile was determined in various types of IM. The intestinal type
      of mucin was found only in type I IM while types II and III were characterized by
      the mixed gastrointestinal phenotype with expression MUCSAC and MUC2. It was
      shown that at sites of incomplete IM (types II and III) and atrophic changes of
      GM cells proliferation activity of epithelium is considerably increased; this
      increase may be associated with the risk of developing gastric cancer of the
      intestinal type.

PMID- 20795398
TI  - [Immunophenotype of neoplastic cells and its clinical significance in chronic
      lymphocytic leukemia].
AB  - y We report preliminary results of efficacious clinical application of a new
      immunological method with the use of biochips for diagnosis of chronic
      lymphocytic leukemia. This method has been developed by the authors to detect a
      wide range of cell surface antigens. We compared the amount of cells expressing
      certain antigens with clinical properties of chronic lymphocytic leukemia. Higher
      amounts of CD9, CD21, CD31, CD71, CD38 positive lymphocytes were shown to occur
      in case of favorable course of the disease.

PMID- 20795399
TI  - [Biological models of IgE-dependent bronchial asthma: methodology and prospects
      for application].
AB  - The present work was aimed to review modern approaches to simulation of bronchial
      asthma using laboratory animals. Various modes of immunization and challenge for
      the induction of typical pathological features in mice are described along with
      the methods for detection of these markers (including ones for studying murine
      lung function). Advantages and drawbacks of the models, difficulties and
      prospects of their application for the study of pathogenesis and preliminary
      estimation of the safety and efficacy of antiasthmatic therapy (especially
      antigen-specific immunotherapy) are analyzed. Moreover, the paper presents
      concise characteristic of short-term adjuvant-free murine models of timothy
      pollen extract- and ovalbumin-induced bronchial asthma developed in this country.

PMID- 20795400
TI  - [Actual problems of biology of pancreatic acino-insular cells].
AB  - Acino-insular cells are a distinct type of pancreatic cells sharing structural
      and functional features of both acinar and islet cells. They synthesize and
      secrete digestive enzymes and hormones. Novel concepts of the functional role of
      acino-insular cells and prospects for their further investigation are reviewed.

PMID- 20795402
TI  - [Portrait of a scientist].
AB  - The article is devoted to the analysis of scientific and social activities of
      academician Sergei Severin whose 110th birthday anniversary comes in 2010.
      Severin was a well known Russian scientist, the founder of a biochemical school
      in this country and organizer of the Department of Biochemistry at Lomonosov
      Moscow State University that he headed for 50 years! Severin belonged to a pleiad
      of omniscient scholars having numerous followers and disciples. This essay
      describes his life, creative work and scientific heritage.

PMID- 20795401
TI  - [Modern views of the role of heparin in hemostasis and regulation of enzymatic
      and hormonal activities].
AB  - This review is focused on the role of heparin in the maintenance of hematological
      homeostasis. Description of the main components of the hemostatic system is
      presented. The mechanism of heparin action as an anticoagulating and fibrinolytic
      agent are analyzed. A hypothesis is forwarded to explain the role of heparin in
      animals and humans as a key substance promoting stabilization, regulation and
      distribution of different active blood components bound into complexes with
      heparin.

PMID- 20795403
TI  - [Computer simulation of thyroid regulatory mechanisms in health and malignancy].
AB  - The paper describes a computer model for regulation of the number of thyroid
      follicular cells in health and malignancy. The authors'computer program for
      mathematical simulation of the regulatory mechanisms of a thyroid follicular
      cellular community cannot be now referred to as good commercial products. For
      commercialization of this product, it is necessary to draw up a direct relation
      of the introduced corrected values from the actually existing normal values, such
      as the peripheral blood concentrations of thyroid hormones or the mean values of
      endocrine tissue mitotic activity. However, the described computer program has
      been also used in researches by our scientific group in the study of thyroid
      cancer. The available biological experimental data and theoretical provisions on
      thyroid structural and functional organization at the cellular level allow one to
      construct mathematical models for quantitative analysis of the regulation of the
      size of a cellular community of a thyroid follicle in health and abnormalities,
      by using the method for simulation of the regulatory mechanisms of living systems
      and the equations of cellular community regulatory communities.

PMID- 20795404
TI  - [Specific changes in the phospholipid composition of seminal fluid in male
      infertility].
AB  - High-performance liquid chromatography was used to study the phospholipid
      composition of spermatozoa and sperm plasma in men with fertility disorders. The
      changes in the phospholipid spectrum of both germ cells and its surroundings were
      found to depend on the nature of changes in the spermatogram. The most pronounced
      shifts were common to subjects with asthenozoo-, oligozoo-, and teratozoospermia,
      which may be a cause of infertility.

PMID- 20795405
TI  - [Apolipoprotein E and triglyceride levels in various hepatic functional states].
AB  - Apolipoprotein E (apo-E) was ascertained to affect serum triglycerides levels in
      relation to the hepatic functional state. When apoE values were higher or in the
      normal range, the activity of gamma-glutamyltrasferase (gamma-GT) failed to
      considerably affect serum triglyceride levels. When apo-E values were lower,
      serum triglyceride levels substantially depended on the activity of gamma-GT. The
      highest serum triglyceride levels were noted in men having low apo-E
      concentrations with a high gamma-GT activity.

PMID- 20795406
TI  - [Gastric juice levels of nitric oxide in relation to gastric acidicity in
      patients with upper digestive tract diseases].
AB  - The purpose of the investigation was to study a correlation between gastric
      secretory function and the gastric juice levels of nitric oxide (NO) in patients
      with upper digestive tract diseases. One hundred and seventy-four patients with
      upper digestive tract diseases were examined to solve the set tasks. Analysis of
      the correlation between gastric juice NO levels and gastric secretion volume in
      patients with gastroduodenal diseases indicated that no correlation was found in
      the level of end products of gastric juice NO metabolism and total acidity as an
      aggression factor. At the same time, there was a positive correlation between the
      gastric juice of NO and the volume of basal and stimulated gastric secretion.
      Since during gastric juice secretion, blood supply of the gastric mucosal is
      increased due its dilated microvessels, NO is most likely to cause dilatation and
      accordingly a gastric secretion stimulant. Therefore, by taking into account that
      provision of sufficient gastric mucosal blood supply is one of the protective
      means in gastroduodenal diseases, it may be suggested that in this case NO
      performs a positive role, by participating in gastric protection.

PMID- 20795407
TI  - [The hemostatic system in patients with antiphospholipid syndrome].
AB  - The objective of the investigation was to study the hemostatic system in patients
      with antiphospholipid syndrome (APS). The study enrolled 72 subjects (26 patients
      with APS (mean age 45.5 +/- 10.2 years) and their 46 relatives, including 37 and
      9 first- and- second-degree relatives, respectively; mean age 29.5 +/- 16.4
      years) from 26 families. A battery of standardized tests was used to evaluate the
      hemostatic system. At the examination, most relatives were found to have signs of
      thrombophilia: activated intravascular coagulation and suppressed fibrinolysis.
      The high detection rate for lupus anticoagulant (LA) amongst the relatives of
      patients with APS (39.1%) is likely to suggest its heritability. Logistic
      regression analysis showed the prognostic value of thrombocytic aggregatory
      disorders in the development of hemorrhagic manifestations, as well as an
      association of LA and thrombocytopenia.

PMID- 20795408
TI  - [Progress in methods for the transcutaneous wireless energy supply to implanted
      ventricular assist devices].

PMID- 20795409
TI  - [Cellulose derivative solution ultrafiltration based on track membranes and its
      medical use].

PMID- 20795410
TI  - [A pulse oximeter with the logarithmic photodetector].

PMID- 20795411
TI  - [A system for the quantitative assessment of the human health status].

PMID- 20795412
TI  - [Acupuncture loci and their characteristics assessed using electrical measuring
      instruments].

PMID- 20795413
TI  - [Use of an ultrasonic inhaler for antiseptic treatment of purulent maxillofacial
      wounds].

PMID- 20795414
TI  - Focus of the World Health Day 2010.

PMID- 20795415
TI  - Hepatitis C virus infection among paediatric patients attending University of
      Assiut Hospital, Egypt.
AB  - Few studies have evaluated the epidemiology and risk factors of hepatitis C virus
      (HCV) infection in children in Egypt. This study of 465 children attending Assiut
      University Hospital measured the rates of anti-HCV positivity by 3rd-generation
      ELISA test and of HCV-RNA positivity by PCR, with analysis of some relevant risk
      factors. The rate of HCV-RNA positivity among ELISA-positive cases (n = 121) was
      72.2% overall: 100% in the subgroup with hepatitis, 70.8% in those with a history
      of multiple transfusions and 58.3% in those without hepatitis or multiple
      transfusions. History of blood transfusions, frequent injections, hospitalization
      or surgical procedures were significant risk factors for anti-HCV positivity by
      ELISA.

PMID- 20795416
TI  - Detection of Giardia lamblia antigen in stool specimens using enzyme-linked
      immunosorbent assay.
AB  - The aim of this study in Iraq was to determine the sensitivity and specificity of
      a commercial ELISA test for detection of Giardia lamblia antigen in stool. Of 84
      stool samples from children in Duhok governorate, 42 were positive and 42
      negative for G. lamblia or other parasites by direct and indirect microscopic
      examination. The sensitivity of the ELISA test for detection of G. lamblia versus
      microscopy was 76.4% and the specificity was 100%. We recommend using ELISA in
      epidemiological surveys in Iraq and to confirm the diagnosis in patients with
      typical clinical symptoms of giardiasis but negative results by direct
      microscopy.

PMID- 20795417
TI  - Unusual manifestations of brucellosis: a retrospective case series in a tertiary
      care Greek university hospital.
AB  - Brucellosis remains a diagnostic puzzle. We retrospectively studied the case
      notes of 105 patients with brucellosis who were admitted in the Department of
      Internal Medicine of the University of Patras Hospital, a tertiary care
      institution serving an extended rural area in western Greece, from 2003 to 2006.
      Five unusual causes of brucellosis were identified: hepatic, epidural and thyroid
      abscesses, intrahepatic cholestatic liver disease and pancytopenia. Virtually
      every human organ and system can be involved in brucellosis, which highlights the
      need to include brucellosis in the differential diagnosis, especially in endemic
      areas.

PMID- 20795418
TI  - Effect of metoclopramide on nosocomial pneumonia in patients with nasogastric
      feeding in the intensive care unit.
AB  - This study in the Islamic Republic of Iran aimed to determine whether
      metoclopramide can prevent nosocomial pneumonia in the intensive care unit (ICU).
      Of 220 patients admitted to the surgical ICU who had a nasogastric tube for more
      than 24 hours, 68 case patients received oral metoclopramide (10 mg every 8
      hours) and 152 control patients did not. Similar proportions of cases and
      controls developed nosocomial pneumonia (33.8% versus 33.6%). Endotracheal
      intubation was a risk factor for nosocomial pneumonia (odds ratio 7.70). There
      were no significant differences between groups in mortality rate or time of onset
      of nosocomial pneumonia. Metoclopramide appears to have no effect on the
      development of nosocomial pneumonia with nasogastric feeding.

PMID- 20795419
TI  - Metabolic syndrome in patients with hypertension attending a family practice
      clinic in Jordan.
AB  - Metabolic syndrome is being reported more frequently in the Eastern Mediterranean
      region. Patients with hypertension attending family practice clinics in the
      University of Jordan Hospital between February and July 2006 were assessed for
      the frequency of metabolic syndrome and its individual components. Of 345
      patients studied, 65% had metabolic syndrome. Females were more likely to meet
      Adult Treatment Panel-III criteria for the diagnosis. Diabetes mellitus was the
      most frequent component of metabolic syndrome in males, while low serum high
      density lipoprotein cholesterol and high waist circumference ranked first and
      second in females. Primary care providers should be alert to the importance of
      screening patients with hypertension for metabolic syndrome to prevent and manage
      these combined conditions.

PMID- 20795420
TI  - Frequency of haemoglobinopathies at premarital health screening in Dohuk, Iraq:
      implications for a regional prevention programme.
AB  - beta-thalassaemia major and sickle-cell disease are important health problems in
      Iraq. To provide information for a prevention programme, the frequency of
      haemoglobin disorders was mapped in Dohuk governorate. A total of 591 couples
      (1182 individuals) attending health centres for premarital health screening were
      tested; 44 (3.7%) were found to be carriers of ,-thalassaemia, 14 (1.2%) of the
      sickle-cell gene and 1 (0.1%) of deltabeta3-thalassaemia. A total of 3 couples
      (i.e. 5/1000) were at risk of having a child with beta-thalassaemia major, and
      the estimated number of affected children with a major haemoglobinopathy was 39
      per year. The findings stress the importance of a regional prevention programme
      for haemoglobinopathies based on premarital screening, counselling and prenatal
      diagnosis.

PMID- 20795421
TI  - Comparison of peak expiratory flow rates applying European and Iranian equations
      to Palestinian students.
AB  - Measurement of peak expiratory flow rate (PEFR) is required for effective asthma
      treatment, but ethnic differences affect the application of prediction equations
      for lung function. PEFR was measured in a representative sample of 1000 students
      in Nablus, Palestine. Predicted PEFR equations for Europeans and Iranians were
      applied to both males and females in age groups < 21 and > or = 21 years. There
      was a statistically significant correlation between the predicted PEFR values in
      Palestinians and both equations in both males and females regardless of age.
      Equations developed on Iranians were more useful for Palestinians than the
      European equations, but there is a need to develop our own nomograms.

PMID- 20795422
TI  - Menarcheal age of mothers and daughters: Tehran lipid and glucose study.
AB  - There is some evidence for a decreasing age of menarche in many populations. This
      study examined the secular trend of age at menarche among Iranian women. Age at
      menarche based on recall information was recorded for 770 pairs of mother and
      daughters. Between 1930 and 1990 mean menarcheal age of this cohort of women
      decreased from 13.88 to 12.98 years (-0.15 years per decade) and mean height of
      the cohort increased from 152.33 to 158.43 cm (+0.99 cm per decade). There was a
      significant correlation between menarcheal age of mothers and their daughters (r
      = 0.27). Year of birth, mother's menarcheal age and daughter's height were
      significant predictors of daughter's menarcheal age.

PMID- 20795423
TI  - Impact of preconception health education on health locus of control and self
      efficacy in women.
AB  - The preconception period is an ideal opportunity to optimize women's health. This
      study of women attending premarital clinics in the Islamic Republic of Iran aimed
      to evaluate the impact of a health education workshop on their health locus of
      control and self-efficacy in physical activity. The design was a randomized
      controlled trial with a questionnaire before and after the intervention. At post
      intervention, there were significant increases in scores of internal health locus
      of control and self-efficacy in the experimental group (n = 109) compared to the
      control group (n = 101). It was concluded that a short-term health education may
      empower women to adopt healthy lifestyles.

PMID- 20795424
TI  - Knowledge and practices of pregnant women about folic acid in pregnancy in Abu
      Dhabi, United Arab Emirates.
AB  - This study assessed the knowledge and practices about folic acid in pregnancy
      among pregnant women attending 2 main maternal and child health centres in Abu
      Dhabi. The majority of the 277 interviewed mothers (79.1%) had heard of folic
      acid and 46.6% had accurate knowledge about the role of folate in preventing
      neural tube defects. There were good practices regarding folate supplementation
      in the current pregnancy; most of the interviewed mothers took it daily and in
      the recommended dose. However, only a minority took it prior to pregnancy.
      Education, irrespective of age or parity, was the major factor determining better
      knowledge of folic acid in pregnancy.

PMID- 20795425
TI  - Effect of Clupeonella grimmi (anchovy/kilka) fish oil on dysmenorrhoea.
AB  - To examine whether dietary supplementation with omega-3 fatty acids from
      Clupeonella grimmi can relieve symptoms of dysmenorrhoea, we carried out a cross
      over clinical trial on 36 girls aged 18-22 years. They were randomly allocated
      into 2 groups of 18. Group A received 15 mL fish oil daily (550 mg
      eicosapentaenoic acid; 205 mg decosahexaenoic acid) while Group B received
      placebo. After 3 months, the treatment regimens were swapped. The treatment
      groups reported a significant difference after 3 months of supplementation with
      fish oil (visual analogue scale score 20.9 compared with 61.8 for the placebo (P=
      0.001). There was also a marked reduction in low back pain and abdominal pain (P
      < 0.05), and participants needed significantly fewer rescue doses of ibuprofen
      while using fish oil.

PMID- 20795426
TI  - [Comparison of the calcium intake during and before Ramadan in Marrakesh,
      Morocco].
AB  - We studied the effect of Ramadan fasting on calcium intake in 2 groups of 500
      healthy subjects from Marrakesh using the colloquial Arabic version of the
      Fardellone questionnaire. The first group was investigated 5 months before
      Ramadan and the second during Ramadan. No significant difference was observed
      between the 2 groups. However, comparison of the pre-Ramadan and Ramadan periods
      for each age group showed a significant increase in calcium intake in subjects
      over 60 years. During Ramadan, consumption of milk was significantly higher,
      while consumption of other dairy products was not different. Overall, no
      significant difference in calcium intake was noted between pre-Ramadan and
      Ramadan periods.

PMID- 20795427
TI  - Lesional skin vascular endothelial growth factor levels correlate with clinical
      severity in patients with cement allergic contact dermatitis.
AB  - Allergic contact dermatitis to cement is a delayed-type hypersensitivity reaction
      in which cytokines interferon-gamma (IEN-y) and vascular endothelial growth
      factor(VEGF) may be involved in persisting erythema and oedema. VEGF and IFN
      gamma levels in serum and skin lesions were measured in 32 Egyptian building
      workers with chronic allergic contact dermatitis due to occupational exposure to
      cement and 20 healthy controls. Dermatitis patients had significantly higher
      levels of serum and lesional skin VEGF and IFN-gamma than controls. A significant
      positive correlation was found between tissue VEGF and the eczema area and
      severity index (EASI) score in dermatitis patients (r = 0.86). VEGF and IFN-gamma
      may play a role in the pathogenesis of cement allergic contact dermatitis.

PMID- 20795428
TI  - Profile of childhood blindness and low vision in Yemen: a hospital-based study.
AB  - ABSTRACT A retrospective review of records determined the frequency and causes of
      low vision and blindness in all children aged < 16 years attending an ophthalmic
      practice in Sana'a, Yemen between January and December 2001. Of the 1104 children
      studied, 45 (4.1%) were found to have bilateral blindness and 115 (10.4%) were
      unilaterally blind; 48 children (4.3%) were bilaterally visually impaired and 109
      (9.9%) were unilaterally visually impaired. The main causes of bilateral
      blindness included cataract, glaucoma and retinal disorders. The most common
      causes of bilateral low vision included refractive errors, keratoconus and
      retinal disorders. These results provide a basis for planning blindness
      prevention programmes in Yemen.

PMID- 20795429
TI  - Relationship between overall and abdominal obesity and periodontal disease among
      young adults.
AB  - To assess overall and abdominal obesity and their relation to periodontal disease
      among young adults, body mass index (BMI) and waist circumference (WC) were
      measured and clinical attachment loss (CAL), gingival index (GI) and Community
      Periodontal Index (CPI) were estimated. The sample comprised 380 adults (170
      males and 210 females) aged 20-26 years. There was a significant correlation
      between both BMI and WC and CAL, GI and CPI in females. In males, a significant
      correlation was only recorded between WC and GI and CPI. Overall and abdominal
      obesity in young adult females and abdominal obesity in males were significantly
      associated with periodontal disease.

PMID- 20795430
TI  - Burnout among clinical dental students at Jordanian universities.
AB  - Dentistry is a profession demanding physical and mental efforts as well as people
      contact, which can result in burnout. The level of burnout among 307 clinical
      dental students in 2 Jordanian universities was evaluated using the Maslach
      Burnout Inventory survey. Scores for the inventory's 3 subscales were calculated
      and the mean values for the students' groups were computed separately. Dental
      students in both universities suffered high levels of emotional exhaustion and
      depersonalization. The dental students at the University of Jordan demonstrated a
      significantly higher level of emotional exhaustion than their counterparts at the
      Jordan University of Science and Technology.

PMID- 20795431
TI  - Snake bite envenomation: experience at King Abdulaziz Medical City, Riyadh.
AB  - We surveyed the records of 21 of the 28 snakebite victims seen at King Fahad
      National Guard Hospital in Riyadh over the 20-year period 1986-2005. The most
      common symptoms were local pain and swelling and the most common signs oedema and
      tenderness. Neurotoxicity was not noted in any case. Coagulopathy was recorded
      for 14/21 patients (66.7%) and 5/19 (26.4%) had leukocytosis. All patients were
      given tetanus toxoid (100%) and 20 (95.2%) received antivenom. Blood products
      were administered in 2 cases and prophylactic antibiotics in 10 (47.6%). No
      allergic reaction to antivenom was reported.

PMID- 20795432
TI  - Disclosing the truth to terminal cancer patients: a discussion of ethical and
      cultural issues.
AB  - One of the most difficult ethical dilemmas facing health care professionals
      working in oncology is whether, when, how and how much to tell terminal cancer
      patients about their diagnosis and prognosis. The aim of this article is to
      review the trends in this issue worldwide. While a majority of physicians in both
      developed and developing countries tell the truth more often today than in the
      past, the assumption that truth-telling is always beneficial to patients can be
      questioned. The issue of truth-telling is still approached differently in
      different countries and cultures and there is a need for an increased awareness
      of cultural differences to truth-telling among patients from ethnic minorities.

PMID- 20795433
TI  - Paravertebral abscess and neurological deficits in cervical brucellar
      spondylitis.

PMID- 20795435
TI  - WHO Regional Director visiting Pakistan: high level policy dialogue on key public
      health strategic policies and programmes.

PMID- 20795434
TI  - Penile juvenile xanthogranuloma and neurofibromatosis type-1: risk association
      with juvenile myelomonocytic leukaemia?

PMID- 20795436
TI  - AIDS awareness and attitudes among Yemeni young people living in high-risk areas.
AB  - Despite te low rate of infection in Yemen, there are concerns about the possible
      spread of HIV among high-risk and vulnerable groups. A community-based study was
      made in 2005 of AIDS awareness and attitudes among 601 young people aged 15-24
      years from low-income, high-risk neighbourhoods in Aden. Young people lacked
      proper information about HIV/AIDS. Although 89% had heard of AIDS, fewer (46%)
      could name 3 ways of transmission or 3 ways to avoid infection (28%).
      Misconceptions about modes of transmissions were prevalent and many young people
      believed that they faced little or no risk. There were intolerant attitudes
      towards AIDS patients. About half the young people knew that prostitution and
      homosexuality existed in their area.

PMID- 20795437
TI  - HIV/AIDS surveillance in Egypt: current status and future challenges.
AB  - By international standards, HIV/AIDS prevalence is low in Egypt (< 0.1%).
      However, questions about the accuracy of this figure are coupled with fears of an
      imminent increase in prevalence, with evidence suggesting that, despite Egypt's
      conservative culture, high-risk behaviour is more widespread than commonly
      reported and the country's changing socioeconomic context is perpetuating this
      trend. Through an analysis of the current HIV/AIDS surveillance system in Egypt,
      this paper explores some of the unique challenges this country faces in dealing
      with the HIV/AIDS epidemic. It concludes that constraints, such as Egypt's
      cultural norms and laws, the population's lack of knowledge about HIV/AIDS and
      the bureaucratic health system, hinder the development and implementation of
      effective surveillance systems.

PMID- 20795438
TI  - Evidence-based approach to HIV/AIDS policy and research prioritization in the
      Islamic Republic of Iran.
AB  - In formulating the second national strategic plan for prevention of HIV/AIDS in
      the Islamic Republic of Iran a more evidence-based approach was needed. This
      paper reports on a systematic review of the local evidence about the determinants
      of HIV/AIDS transmission in 3 categories: poor knowledge and negative attitudes
      about HIV transmission; injection drug use; and sexual promiscuity. Of 93 reports
      reviewed, 53 met the inclusion criteria. Information about the prevalence and
      magnitude of effect for the 3 risk determinants at the national and regional
      level was scarce. Heterogeneity between studies, even in the same sub-population,
      was significant. An improved research base and better sharing of information are
      needed within countries of the Eastern Mediterranean Region.

PMID- 20795439
TI  - Changes in tobacco use among 13-15-year-olds between 1999 and 2007: findings from
      the Eastern Mediterranean Region.
AB  - This report focuses on change over time in tobacco use among adolescents in
      countries included in the Eastern Mediterranean Region (EMR) of the World Health
      Organization. The Global Youth Tobacco Survey (GYTS) was conducted in each site
      at least twice between 1999 and 2007. Results indicate that for students aged 13
      15 years tobacco use is a major public health problem. Increase in the use of
      water pipe, the likely initiation of smoking by never smokers, and a potential
      increase in tobacco use among young girls was found in most of the EMR sites. The
      results from the GYTS can be used by all of the EMR countries involved to set
      their tobacco control programme and policy agenda

PMID- 20795440
TI  - Assessing validity of the adapted Arabic Paediatric Asthma Quality of Life
      Questionnaire among Egyptian children with asthma.
AB  - The recent focus in asthma management is rendering children a better quality of
      life (QOL). Validity and reliability of an adapted Arabic translation of the
      Paediatric Asthma Quality of Life Questionnaire (PAQLQ-A) among Egyptians was
      assessed in a cohort of 103 asthmatic children aged 8-16 years. Discriminative
      validity of mean scores was significantly higher among mild asthmatics than those
      with moderate/severe asthma. Construct validity of domains was significantly
      negatively correlated with clinical severity score. Reliability and internal
      consistency were assessed using Cronbach alpha coefficient (alpha = 0.84).
      Reproducibility and responsiveness were high among both stable and unstable
      asthma patients. PAQLQ-A is valid and reliable for assessing QOL among Egyptian
      asthmatic children.

PMID- 20795441
TI  - Cigarette smoking, hypertension and diabetes mellitus as risk factors for
      erectile dysfunction in upper Egypt.
AB  - Erectile dysfunction impairs the quality of life of millions of men worldwide.
      This study aims to determine the relationship between selected clinical risk
      factors and erectile dysfunction in men residing in upper Egypt. Patients were
      surveyed with the 5-item International Index of Erectile Function (IIEF-5) and
      assessed for the presence of hypertension, diabetes and smoking. Of 658 men with
      erectile dysfunction, 17.3% had hypertension, 21.4% had diabetes and 40.1% were
      smokers, whereas among 821 age-matched controls without erectile dysfunction, the
      corresponding figures were 2.8%, 3.7% and 28.7%. Multivariate analysis showed
      that hypertension (OR = 5.4), diabetes mellitus (OR = 5.4) and smoking (OR = 3.1)
      were significant risk factors for erectile dysfunction.

PMID- 20795442
TI  - Behavioural and clinical factors associated with depression among individuals
      with diabetes.
AB  - Depression has been linked to greater mortality and morbidity in diabetic
      patients, but this issue has not been adequately studied in the Islamic Republic
      of Iran. This cross-sectional study described the prevalence of depression in
      patients attending a diabetes clinic in Urmia and determined the associated
      sociodemographic, behavioural and clinical factors. Of 295 patients, 128 (43.4%)
      had depression scores (> or = 15) on the Beck Depression Inventory. The mean
      score for all patients was 15.4 (SD 9.5). Those with depression were
      significantly older and less educated than those without depression, had a longer
      duration of diabetes and were more likely to suffer complications. On logistic
      regression analysis, older age was the only variable significantly associated
      with depression.

PMID- 20795443
TI  - Profile of diabetic ketoacidosis at a teaching hospital in Benghazi, Libyan Arab
      Jamahiriya.
AB  - This study describes the profile of 100 cases of diabetic ketoacidosis (DKA) at a
      teaching hospital in 1 Benghazi, Libyan Arab Jamahiriya. DKA was more frequent in
      young women with type 1 diabetes and mostly due to preventable causes, e.g.,
      disrupted insulin treatment and/or infection. DKA also occurred in type 2
      diabetics, with a higher mortality rate, as they were older patients with co
      morbidity. Polyurea, fatigue, abdominal pain and vomiting were the most common
      clinical features, while coma was rarer. A high number of cases were first
      presentations of type 1 diabetes; hence this diagnosis should be considered in
      all patients with acute abdomen or decreased level of consciousness. The reasons
      for high mortality rate in this study (10%) were multifactorial.

PMID- 20795444
TI  - Efficacy of metoclopramide and dexamethasone for postoperative nausea and
      vomiting: a double-blind clinical trial.
AB  - Postoperative nausea and vomiting are common complications of anaestnesia. This
      double-blind clinical trial assessed the incidence of nausea and vomiting after
      cataract surgery with intravenous anaesthesia in 100 patients randomly assigned
      to preinduction placebo (saline), metoclopramide (10 mg), dexamethasone (8 mg) or
      the 2 drugs combined. The incidence of nausea in the recovery room was 44% with
      placebo, 20% with metoclopramide, 16% with dexamethasone and 8% with the
      combination. The incidence of vomiting was 20%, 4%, 4% and 0% respectively in the
      4 groups. Metoclopramide plus dexamethasone combination significantly decreased
      nausea and vomiting both in the recovery room and 24 hours afterwards and is
      recommended for high-risk groups, especially in outpatient surgeries.

PMID- 20795445
TI  - Chlamydia trachomatis and cervical intraepithelial neoplasia in married women in
      a Middle Eastern community.
AB  - The objective of this study was to determine the association between vaginal
      Chlamydia infection and cervical intraepithelial neoplasia (CIN). Data were
      collected in a case-control study for 60 patients with CIN in biopsy and 85
      control subjects with normal colposcopy and biopsy. Serum antibodies to C
      trachomatis were associated with an increased risk for CIN [odds ratio (OR) =
      7.3; 95% confidence interval (CI) 1.5-35.2)]. There was also a significant
      association between presence of inclusion bodies for C. trachomatis and CIN (OR =
      5.5; 95% CI 2.4-12.4). These results indicate a strong association between CIN
      and chlamydial cervicitis.

PMID- 20795446
TI  - Pregnancy outcome in women with antiphospholipid syndrome on low-dose aspirin and
      heparin: a retrospective study.
AB  - This retrospective review of hospital records analysed pregnancy outcome with 2
      different treatments for women with recurrent miscarriage diagnosed with
      antiphospholipid syndrome in the index pregnancy. Of 64 women, 29 had received
      aspirin and 35 aspirin plus heparin. Pregnancy-induced hypertension, prematurity,
      intrauterine growth restriction and neonatal death were considered as maternal
      and fetal complications. There were no significant differences in antenatal and
      maternal complications between the groups. HOwever, there were significant
      differences in mean anticardiolipin IgG antibody levels. Aspirin alone or in
      combination with parin was equally efficacious in women with antiphospholipid
      syndrome and recurrent miscarriage.

PMID- 20795447
TI  - Accuracy of ultrasound, clinical and maternal estimates of birth weight in term
      women.
AB  - Accurate prenatal estimation of birth weight is useful in the management of
      labour and delivery. This study compared the accuracy of ultrasound, clinical and
      maternal estimates of fetal weight in 246 parous women with singleton, term
      pregnancies admitted for scheduled caesarean section. The sensitivity and
      specificity of predicting birth weight by ultrasound measures were 12.6% and
      92.1%, by clinical palpation were 11.8% and 99.6% and by maternal estimate were
      6.3% and 98.0% respectively. Clinicians' estimates of birth weight in term
      pregnancy were as accurate as routine ultrasound estimation in the week before
      delivery. Parous women's estimates of birth weight were more accurate than either
      clinical or ultrasound estimation.

PMID- 20795448
TI  - Road traffic fatalities in Qatar, Jordan and the UAE: estimates using regression
      analysis and the relationship with economic growth.
AB  - Smeed's equation is a widely used model for prediction of traffic fatalities but
      has been inadequate for use in developing countries. We applied regression
      analysis to time-series data on vehicles, exponential models for fatality
      prediction, producing an average absolute error of 20.9% for Qatar, 10.9% for
      population and traffic fatalities in the United Arab Emirates (UAE), Jordan and
      Qatar. The data were fitted to Jordan and 5.5% for the UAE. We found a strong
      linear relationship between gross domestic product and fatality rate.

PMID- 20795450
TI  - Gender-specific oral health attitudes and behaviour among dental students in
      Palestine.
AB  - This study assessed gender differences in oral health knowledge, attitude and
      behaviour among undergraduate dental students in Palestine. Students aged 18-22
      years at Al Quds University (n=260) completed the English version of the
      Hiroshima University-Dental Behavioral Inventory. Females had more positive
      dental health attitudes and behaviours (making regular visits the dentist, being
      more educated about professional toothbrushing and taking more care with brushing
      their teeth). Half the students of both sexes thought they could not avoid having
      false teeth when they were old. Some aspects of oral health behaviour and
      attitudes were different between males and females, but in other aspects
      professional training may have compensated for these differences.

PMID- 20795449
TI  - Drug prescription habits in public and private health facilities in 2 provinces
      in South Africa.
AB  - The aim of this study was to explore drug prescription habits using WHO standard
      indicators in public hospitals and 36 private surgeries in 2 provinces in South
      Africa. A high mean number of drugs were prescribed per patient (3.2 versus 2.8)
      in public hospitals and by general practitioners (GPs) respectively andc generic
      prescribing rates were low (45.2% versus 24.5%). The rates of prescribing in
      public hospitals and by GPsa were 8.3% versus 23.3% for injections, 68.1% versus
      31.9% for antibiotics and 92.6% versus 68.5% for drugs from the essential drugs
      list. Drug prescribing in both sectors needs to be regulated, especially the use
      of antibiotics, essential drugs and generic prescribing.

PMID- 20795451
TI  - Amalgam use and waste management by Pakistani dentists: an environmental
      perspective.
AB  - To assess amalgam use and waste management protocols practised by Pakistani
      dentists, a cross-sectional study was made of 239 dentists in Islamabad and
      Rawalpindi, recruited by convenience and cluster sampling. Amalgam was the most
      frequently used restorative material, with the choice dictated by patients'
      financial constraints. While 90.4% of dentists perceived amalgam as a health
      risk, only 46.4% considered it an environmental hazard. The majority disposed of
      amalgam waste in the trash, down the sink or as hospital waste. Very few (5.9%)
      had an amalgam separator installed in their dental office. Amalgam waste
      management protocols and mercury recycling should be introduced in Pakistan.

PMID- 20795452
TI  - Disseminated leishmaniasis caused by Leishmania tropica in HIV-positive patients
      in the Islamic Republic of Iran.

PMID- 20795453
TI  - Lupoid leishmaniasis due to Leishmania major with remaining large scars: report
      of 2 cases.

PMID- 20795454
TI  - A case of Behcet disease with pulmonary artery pseudoaneurysm: long term follow
      up.

PMID- 20795455
TI  - Ascaris lumbricoides infection: an unexpected cause of pancreatitis in a western
      Mediterranean country.

PMID- 20795456
TI  - HPV vaccine for prevention of cervical cancer: key issues and challenges for
      developing countries.

PMID- 20795457
TI  - A scenario of cervical carcinoma in a cancer hospital.
AB  - INTRODUCTION: Cervical carcinoma is an important women's health problem
      throughout the world. There are very few published data on this disease in Nepal.
      We wanted to study the pattern of cervical carcinoma based on hospital data.
      METHODS: A 10 years retrospective study of scenario of cervical carcinoma was
      conducted. The data have been analyzed according to age, occurrence of other
      cancers, histological type, religion, risk factors and district wise. RESULTS:
      The number of cervical carcinoma showed a rising pattern over the 10 year period.
      The median age of the patients was 45 years and maximum frequency (33%) of cases
      were found in the age group 40 to 49 years. Squamous cell carcinoma comprised 40%
      of cases, Adenocarcinoma 4% and 1.1% cases were of mixed variety. 92% of cases
      were Hindu by religion. 43% of patients were smoker in our study, 5% had positive
      family history. Chitwan with 7.35% had the maximum number of cases followed by
      Rupandehi with 6.40% and Nawalparasi with 5.41%. CONCLUSIONS: The cancer pattern
      revealed by the present study provides valuable leads to cervical cancer
      epidemiology in Nepal. Routine cytological screening of the population for
      cervical cancer is highly necessary for its early detection and treatment.

PMID- 20795458
TI  - Behavioral risk factors for non-communicable disease among factory employees in
      Faridabad; Haryana.
AB  - INTRODUCTION: In developing countries like India, in addition to the infectious
      diseases, non-communicable diseases are emerging as significant causes of
      morbidity and mortality. Workplaces present a setting which is appropriate for
      intervention for adults in a community. The aim of this study is to assess the
      knowledge, attitude and prevalence of selected risk factors for non-communicable
      diseases. METHODS: A cross sectional study was conducted among the regular
      employees of the factories. Smoking, alcohol consumption, dietary intake and
      physical activity were measured through interview schedules and height, weight
      and blood pressure were also measured by standard instrument. An awareness
      generation program was pre-tested. RESULTS: A total of 545 employees were
      interviewed. Among them 307 (56.3%) and 238 (43.7%) were manual and non-manual
      workers respectively. Most of the employees knew [smoking as a risk factor for
      hypertension (55.2%), heart attack (61.1%) and cancer (78.7%); Alcohol as a risk
      factor for hypertension (72.1%), heart attack (73.9%), cancer ( 54.9%); Physical
      inactivity as a risk factor for hypertension (82.6%), heart attack (78.5%),
      diabetes (60.4%) and high fat diet as a risk factor for hypertension (67.2%),
      heart attack (64.8%)] that these risk factors lead to different non-communicable
      diseases. The prevalence (95% CI) of the risk factors is as follows: male current
      smoker [40.7% (36.4-45.3)], current alcohol consumption [31.0 % (27.2 - 35.1)],
      sedentary activity [41.2% (37.0 - 45.5)], high fat intake [93.7% (90.2 - 95.5)],
      over weight [26.9% (23.2 - 30.9)]; and hypertension [21.0% (17.62 - 24.6)]
      CONCLUSIONS: This study showed that the risk factors for non-communicable
      diseases are prevalent in factory employees. Implementation of the risk factors
      control programme is desirable and there is an interest among employees and
      management.

PMID- 20795460
TI  - A pattern of age-related macular degeneration.
AB  - INTRODUCTION: Age related macular degeneration is a disorder of the macula most
      often clinically apparent affecting central vision and is one of the leading
      causes of blindness in the population above 50 years. The aim of this study is to
      determine clinical profile of AMD in Nepalese presenting to a Teaching Hospital
      in Kathmandu. METHODS: It was a hospital-based cross-sectional study. The
      subjects included in the study were those presenting to the Ophthalmology
      department of Kathmandu Medical College Teaching Hospital from July 2007- Dec
      2007.The total number of individuals included in the study were 402 and total
      number of eyes were 804. RESULTS: AMD was observed in 5.2% out of 402 subjects of
      40 years and above age group with prevalence increasing with age. The prevalence
      of AMD was 0.7% within 40-50 years of age-group individuals increasing to 2.6% in
      51-60 years, 6.5% in 61-70 years and to 19.3% among subjects above 71 years. This
      study revealed that the prevalence of AMD in females was higher with female
      preponderance in ratio of 2.5:1. 52.5 % AMD subjects in our study had visual
      impairment with 6/246/60 vision and 15% had vision <3/60-PL. Our study revealed
      statistically significant increased risk for AMD with aging (p=0.00). Increased
      risk was observed in female gender and diabetics though the Odds ratio (OR) was
      statistically insignificant (p=>0.01). CONCLUSIONS: Prevalence of AMD in Nepalese
      presenting to Kathmandu Medical College Teaching Hospital was 5% with female
      preponderance in ratio of 2.5:1. Aging showed statistically significant increased
      risk for AMD development in this study.

PMID- 20795459
TI  - A study of injuries and violence related articles in Nepal.
AB  - INTRODUCTION: Nepal lacks sufficient data on injury and violence. Studies have
      been done in different regions but there is not a nationwide study on this topic.
      So, we have designed this systematic review to get a cumulative picture of injury
      and violence status in Nepal. METHODS: We searched Medline database, Google
      scholar database and also all the national medical journals for relevant studies
      on injuries and violence. Our eligibility criteria included studies done in
      Nepal, evaluating the incidence of different forms of injuries, and their causes
      and effects. We excluded case reports, editorials and reviews. All together, we
      had 23 studies. We made cumulative analysis wherever possible. RESULTS: All the
      studies were descriptive. In overall, the incidence of injuries was twice as
      common in male as in female with the ratio of 2.1:1. The economically active
      population between 20-50 years of age was mostly involved in injuries. Road
      traffic injuries were the most common form of injuries, most of which (42.5%)
      involved motorcycles. Pedestrians (48.6%) were the most vulnerable group of
      population. Falls (48.9%) were the most common cause of neuro traumatic
      accidents. CONCLUSIONS: Our systematic review suggests that injuries and violence
      pose a big problem; road traffic accidents make the most part of it.

PMID- 20795461
TI  - The role of simulator Promis2 in learning laparoscopic skill.
AB  - INTRODUCTION: Laparoscopic surgery is unique and complex in nature, so the
      training is necessary before proceeding to operation room. Many computer aided
      simulators have been developed for the purpose. Our objective is to assess the
      improvement of basic laparoscopic skills after training in simulator. METHODS:
      The fifth year medical students underwent training of three laparoscopic skills
      using Promis2 simulator twice weekly for 4-6 weeks. The skills are laparoscopic
      orientation, target pointing and objects transferring. Time, path length of
      instruments and economy of movements were recorded. The comparisons were made for
      these parameters between session first and the last using a Mann-Whitney U test.
      RESULTS: Ten volunteers completed the exercises in less time (186.3 +/- 55.4
      seconds) than the first exercise (215.7 +/- 57.4 seconds) (P=0.0027). Both the
      right and left hand instrument path lengths were also improved from 4425.8 +/-
      1284.3 mm in the first exercise to 3925.3 +/- 1313.6 mm in the last exercise in
      the left side (P=0.0219) and likewise from 4273.8 +/- 1859.4 mm to 3831.3 +/-
      1717.4 mm in the right side (P=0.0027). Economy of the movement in the left
      handed instrument improved from 1114.4 +/- 453.5 mm in the first exercise to
      966.8 +/- 411.1 mm in the last (P=0.0443) and in the right handed instrument from
      845 +/- 398.8 mm to 771.4 +/- 370.5 mm according to the software of Promis2
      simulator (P >0.005). CONCLUSIONS: Training in Promis2 simulator improves the
      basic laparoscopic skills. The candidates become consistently faster with shorter
      path lengths and had smoother instruments movements. They also became
      significantly more consistent in their performance.

PMID- 20795462
TI  - Effect of acute hepatitis E infection in patients with liver cirrhosis.
AB  - INTRODUCTION: Hepatitis E virus is a major cause of enterically transmitted
      hepatitis. Mortality is very high if it is associated with pregnancy, especially
      during third trimester. This study was carried out to find out the effects of
      acute HEV hepatitis on Chronic Liver Disease patients of different etiologies.
      METHODS: The consecutive patients of liver cirrhosis with definite evidence of
      recent HEV infection were enrolled in this study. Acute hepatitis was diagnosed
      by presence of prodromal symptoms and anti-HEV IgM antibody in their serum. The
      outcomes after superinfection with HEV hepatitis were determined by changes in
      Child Pugh score, recovery of liver function test, hospital stay and mortality.
      RESULTS: After exclusion 25 were studied. The etiology of cirrhosis in patients
      was: alcohol 13, autoimmune hepatitis 3, hepatitis B 2, Budd Chiari syndrome 2,
      alcohol plus hepatitis B 1, hepatitis C 1, cardiac cirrhosis 1, Wilson's disease
      1 and cryptogenic 1. All patients with no recent decompensation showed signs of
      decompensation during admission. Seven (28%) patients died. The cause of death
      was either upper gastrointestinal bleeding or hepatorenal syndrome. Remaining
      patients had prolonged hospital stay with deterioration of Child-Pugh's score.
      CONCLUSIONS: Superinfection of HEV in cirrhotic patient causes rapid
      decompensation. The morbidity and mortality is higher compared to those non
      infected patients. Development of hepatorenal syndrome and upper GI bleeding was
      commonest cause of death.

PMID- 20795463
TI  - Diagnosis of tubercular lymphadenopathy by fine needle aspiration cytology, acid
      fast staining and mantoux test.
AB  - INTRODUCTION: This study was undertaken to evaluate the role of Ziehl-Neelsen
      stain (for acid-fas bacilli), and Mantoux test in diagnosing tubercular
      lymphadenopathy on FNAC. METHODS: FNAC was performed on patient with superficial
      lymphadenopathy. Ziehl-Neelsen stain for acid fast bacilli was done in all cases
      where cheesy or purulent material was aspirated and smear showed granulomatous
      lymphadenitis. A Mantoux test was also done in these patients. A Mantoux test was
      further done in patients of reactive lymphadenopathy where the lymph node size
      was more than 1 cm. If the result was positive, a repeat FNAC was performed. When
      the repeat FNAC showed ill-defined granulomas, excision biopsy was done. RESULTS:
      Tubercular lymphadenopathy was seen in 122 (48.2%) cases. Acid- fast bacilli were
      found in 71 (58.1%) cases. Mantoux test was positive in 112 (91.8%) cases. A
      repeat FNAC was done in seven of 11 patients where the cytologic features of
      tuberculosis were not seen but the lymph node size was more than 1 cm and Mantoux
      test was positive. The repeat FNAC showed ill-defined granulomas without
      necrosis. Excision biopsy done in these patients diagnosed them as tubercular
      lymphadenitis in five of the seven cases, the remaining two cases being diagnosed
      as reactive lymphadenitis. CONCLUSIONS: FNAC coupled with Ziehl - Neelsen
      staining for AFB and Mantoux test improves the diagnostic efficiency for
      tubercular lymphadenopathy.

PMID- 20795464
TI  - Antibiotic susceptibility pattern of nosocomial isolates of staphylococcus aureus
      in a tertiary care hospital, Nepal.
AB  - INTRODUCTION: Methicillin resistant Staphylococcus aureus (MRSA), the most common
      cause of nosocomial infection has been a major cause of morbidity and mortality
      around the world. They are normally resistant to most of the antibiotics used in
      clinical practice. This study has been carried out to find out the resistance
      pattern among S. aureus. METHODS: During November 2007 to June 2008, clinical
      samples from patients with nosocomial infection were processed for culture and
      sensitivity following standard methodology in microbiology laboratory, Tribhuvan
      University teaching hospital, Kathmandu, Nepal. RESULTS: Among 149 Staphylococcus
      aureus isolates, highest resistance was observed against Penicillin (91.94%)
      followed by Fluoroquinolone (61.74%), Erythromycin (52.94%), Gentamicin (46.98%),
      Cotrimoxazole (42.95%), Tetracycline (40.94%) and others, whereas susceptibility
      was observed maximum against Chloramphenicol (94.85%) followed by Rifampicin
      (92.61%), Tetracycline (59.06%), Cotrimoxazole (57.04%), and others. None of the
      isolates were resistant to Vancomycin and Teicoplanin. Of these isolates 44.96 %
      of the isolates were Methicillin resistant S. aureus (MRSA). Resistance to
      Penicillin, Fluoroquinolone, Erythromycin, Gentamicin, Co-trimoxazole and
      Tetracycline were associated significantly with MRSA isolates (chi2= 8.779,
      p<0.05, chi2= 74.233, p<0.05, chi2= 84.2842, p<0.05, chi2= 108.2032, p<0.05,
      chi2= 88.1512, p<0.05 and chi2= 79.1876, p<0.05 respectively). Although most of
      the Methicillin sensitive S. aureus (MSSA) isolates were susceptible to both
      Rifampicin and Chloramphenicol, only Rifampicin susceptibility was significantly
      associated with them (chi2= 10.1299, p<0.05). Among three Biochemical tests for
      the detection of beta lactamase detection namely chromogenic, iodometric and
      acidimetric test, chromogenic test method had highest sensitivity and
      specificity. CONCLUSIONS: Since MRSA comprised a greater part of S. aureus
      isolates and were multi-resistant, patients infected by such strains should be
      identified and kept in isolation for hospital infection control and treated with
      second line of drug like vancomycin.

PMID- 20795465
TI  - Nicorandil induced perianal ulceration.
AB  - Nicorandil is a cardioprotective drug which is used in the prophylaxis and long
      term treatment of angina pectoris. Debilitating perianal ulcer is a rare
      complication of Nicorandil therapy which can cause diagnostic and management
      dilemmas. We describe the management of a case of Nicorandil-induced perianal
      ulcer and review pertinent contemporary literature.

PMID- 20795466
TI  - Lysosomal storage disease.
AB  - We report a case of lysosomal storage disease diagnosed by lysosomal enzyme assay
      in a two year old boy with a history of gradual onset of weakness of body, poor
      vision, flaccid neck and spasticity in all four limbs with hyper-reflexia. On
      fundus examination cherry red spots were noted at macula. On performing lysosomal
      enzyme assay, beta-galactosidase level was considerably low. This indicates that
      the child is affected by lysosomal storage disease most likely GM1
      gangliosidosis. The diagnosis is important because the disease is rare and it may
      be missed as the symptoms are similar to other neurological conditions and the
      diagnosis can help with future conception.

PMID- 20795467
TI  - Twin pregnancy with fetus papyraceous.
AB  - A successful pregnancy outcome with vaginal delivery of a term single live fetus
      in case of twin pregnancy with other twin papyraceous, (vanished in second
      trimester) is an uncommon finding. Ten percent of all perinatal deaths are
      related with dizygotic twins. The rate of intrauterine fetal demise in multiple
      pregnancies is as high as three times of monozygotic. Most frequently used and
      suggested method is follow-up of the maternal coagulation system by a series of
      lab test. Sonography is a visual tool to confirm the diagnosis. In case of
      monofetal death of twin pregnancies, the type of placenta should be analysed and
      then follow up and treatment modalities of these cases should be choosen.

PMID- 20795468
TI  - Omphalocele with dextrotardia-A rare association.
AB  - Omphalocele is frequently associated with many other congenital malformations. In
      cardiac anomalies, association of omphalocele with dextrocardia has been rarely
      noticed before. We present here a child with dextrocardia and omphalocele
      alongwith a brief review of the literature on this rare association.

PMID- 20795469
TI  - Management of breast cancer in Nepal.
AB  - Breast cancer is the second most common malignancy among women in Nepal. It is
      more common in young premenopausal women. Breast cancer continues to increase in
      incidence due to lifestyle changes in Nepalese women despite constant remarkable
      development in the management of this disease over the past three decades. Breast
      cancer was diagnosed solely clinically and surgery was the only treatment option
      until fifty years ago. Multidisciplinary approach has been adopted for diagnosis
      and treatment of breast cancer in Nepal. Imaging is required for the diagnosis,
      appropriate treatment decision and proper follow up. Treatment modality depends
      upon the extent of the disease and tumor biology. However, there is a strong need
      for standard guidelines for the proper management of breast cancer in Nepal so
      that surgeries, chemotherapy, hormone therapy and radiotherapy are standardized
      in the country. Palliative care has been initiated to provide to some patients
      with metastatic breast cancer recently. The breast cancer management in Nepal is
      a little different when compared with the centers in the developed countries. The
      reasons are socioeconomic status, lack of education and lack of facilities.
      Although cancer care is on the rise in Nepal, the optimal facility for centers
      managing breast cancer has to be improved significantly.Cancer education,
      screening and early detection are the key elements to influence the diagnosis,
      treatment and prognosis of breast cancer in Nepal. Breast cancer awareness and
      clinical breast examination are important tools for early detection in our
      resource limited context. Breast cancer can be cured in majority of the cases if
      diagnosed in early stages. This review will focus on relevant patient data along
      with future recommendation regarding breast cancer treatment in Nepal.

PMID- 20795470
TI  - General or specialist surgeons?
AB  - General Surgery is a broad surgical specialty that focuses on diseases related to
      abdominal organs, skins and hernias, both in elective and emergency settings.
      With the prevalent trend for increasing subspecialisation in today's surgical
      practice, general surgery has lost some of its former glory and scope. This has
      led to suffering of the image of the general surgeons (GS) in the eyes of
      trainees, peers, the public and even GS themselves. A comprehensive review of
      literature is presented to address the controversy surrounding the role and
      future of general and specialist surgeons in the current perspectives.

PMID- 20795471
TI  - Minimal invasive anterior decompression in tuberculosis of thoracolumbar junction
      of the spine--experience with SynFrame.
AB  - INTRODUCTION: This study assesses the role of new retractor system SynFrame for
      anterior decompression of tuberculosis of thoracolumbar junction of the spine.
      METHODS: This study includes five consecutive patients with tuberculosis of
      thoracolumbar junction treated with minimal invasive anterior decompression using
      a new table mounted retractor system SynFrame (Stratec Medical, Switzerland). The
      thoracolumbar junction was approached by a left sided thoracotomy. Short
      construct pedicle screw stabilization was done in all cases before decompression.
      The anterior column was reconstructed using expandable cage (n=3) and autologous
      tricortical graft (n=2). RESULTS: The mean operating time was 100 minutes (range
      90-120). Mean overall blood loss was 400 ml. No operation had to change into an
      open procedure. There were neither intra nor postoperative complications related
      to minimal access in particular, nor visceral/vascular complications.
      CONCLUSIONS: The ring retractor system allows minimal open surgery to the spine
      by carrying different devices as well as endoscope, providing an excellent
      visualization of the operating field, and is safe and easy to use. The only
      disadvantage is its high cost.

PMID- 20795472
TI  - [The contribution of glycine and GABA(A) receptors to generation of the
      inhibitory postsynaptic potentials in the frog spinal cord motoneurones].
AB  - The contribution of glycine and GABA(A) receptors to generation of the inhibitory
      postsynaptic potentials (IPSPs) evoked by microstimulation of the inhibitory
      fibers was studied intracellularly in the motoneurones of the isolated frog
      spinal cord. IPSPs were isolated by bloking EPSPs with kynurenate or CNQX and AP
      5. The reversion under the small depolarising current (1-10) nA was used for the
      identification of IPSPs. The selective GlyR antagonist strychnine (1-5 microM)
      reduced the amplitude of IPSPs by a factor of 4.7 on the average in all studied
      motoneurones, while the selective GABA(A)R antagonist bicuculline (50-70 microM)-
      only by a factor of 1.6 and had no effect in 44% of motoneurones. Sequential
      applications of strychnine and bicuculline completely blocked the IPSPs. The
      results suggest that postsynaptic inhibition in the frog motoneurones is mediated
      by glycine (predominantly) and GABA(A) (to a smaller extent) receptors. It is
      possible the GABA(A) receptors are partly extrasynaptic.

PMID- 20795473
TI  - [Age factors in the background electrical activity of the superior cervical
      ganglion neurons in rats].
AB  - Background discharges of single neurons were studied from the superior cervical
      ganglion in newborn, 10-, 20-day-old, 1-, 2- and 6-month-old rats. In all age
      groups, the largest proportion of neurons exhibited aperiodic activity. The
      percentage of neurons with respiratory rhythmic was less. In newborn and 10-day
      old rats, the frequency of discharges was low. Discharge frequency increased in
      20-day-old rats. In 20-day-old and more adult rats, we found neurons bursting
      with cardiac frequency. The means of frequency did not statistically differ in 1
      , 2- and 6-month-old rats. Thus, the pattern of neuronal activity is formed
      during the development in 20-day-old rats. Final maturation of this pattern is
      observed in 1-month-old rats.

PMID- 20795474
TI  - [L-type calcium channel blockers support energy metabolism in rabbit
      cardiomyocytes exposed to general vibration].
AB  - The aim of the paper was to study the mechanism of vibroprotective action of
      nifedipine, a blocker of L-type calcium channels, on cardiomyocytes of a rabbit.
      The enegry-dependent reactions of native mitochondria of rabbit myocardium were
      studied by polarographic method using Clark's type close membrane electrode. The
      changes in functional activity of mitochondria like low energy shift with
      activation of succinate oxidation and inhibition of NAD-depended chain of
      mitochondria breath were observed after prolong common vibration within 56 days.
      Nifedipine 7.5 mg/kg orally activated NAD-dependent site of cell breath and
      reduced hyperactivation of succinate-dependent breath by means of down-up
      mechanism. The positive energotropic effect of nifedipine was accompanied with
      retention of hystomorphological architecture of the myocardium. Therefore,
      nifedipine defends energy metabolism in the myocardium in chronic exposure of
      common vibration.

PMID- 20795475
TI  - [Adaptation reactions of rat blood exposed to low intensity electromagnetic
      radiation].
AB  - It is carried out research of action low-intensive electromagnetic radiations-
      low-intensive laser radiation and radiations of the highest frequency on normal
      animals and at modelling the stress-reaction, caused by introduction of
      adrenaline. Absence of effects of system of blood is noted at action low
      intensive electromagnetic radiations on normal an organism and them correction
      action on alteration an organism, shown in restoration of the broken parameters-
      leukocyte the blood count, electrophoretic mobility of erythrocytes and
      phospholipide's structure of their membranes.

PMID- 20795476
TI  - [Effect of testosterone in Ca2+ mobilization in oocytes and porcine granulose
      stimulated by prolactin and theophylline].
AB  - Influence of testosterone in Ca2+ exchange in oocytes and porcine granulose
      stimulated by prolactin and theophylline was investigated using fluorescent dye
      chlortetracycline. It was shown that prolactin and theophylline separately have
      not affected on the Ca2+ exit from intracellular stores of oocytes. Prolactin and
      theophylline in common stimulate exit of Ca2+ from intracellular stores in
      oocytes, which decreased at presence of inhibitor of protein kinase A. Ca2+ exit
      from intracellular stores of oocytes stimulated by prolactin and theophylline in
      common was inhibited by thapsigargin. In the presence of testosterone prolactin
      and theophylline separately stimulate increasing of cytoplasmic Ca2+
      concentration and exit of Ca2+ from intracellular stores of granulose. Prolactin
      and theophylline in common activate additional exit of Ca2+ from intracellular
      stores in granulose, which decreased in presence of inhibitor of protein kinas C.
      The date obtained suggest differences in regulated mechanisms of cell signaling
      in porcine granulose and oocytes.

PMID- 20795477
TI  - [Effects of social isolation during puberty on reproductive functions and
      behavior of prenatally stressed female rats].
AB  - We studied the consequences of keeping in isolation (1 animal per cage) during
      the puberty period of female rats born from intact mothers or from mothers
      suffering an 1-hour immobilization stress in the last trimester of pregnancy, and
      its influence on oestrous cycle and anxiety level of the adult offspring. There
      were no changes in the rates of anxiety level depending on oestrous cycle phase
      among both control and prenatally stressed females in isolation. On rats moving
      to the groups (4-5 animals per cage) the control rats unlike the prenatally
      stressed individuals show this dependence. About 50 % of the control and
      experimental rats, grown in isolation, are characterized by reduction ofoestrous
      cycle duration (3.3 +/- 0.05 days). The rest of the animals have the normal
      duration ofoestrous cycle (4 +/- 0.3 days), or prolonged duration (5 +/- 0.25
      days). The control rat's oestrous cycle increased because ofdioestrus phase,
      whereas prenatally stressed rats oestrous cycle increased because of estrus
      phase. On females moving to groups the estrous cycle duration of most rats
      increased, but among the prenatally stressed rats there were still females with
      prolonged estrus phase. Besides, the prenatally stressed rats moved from
      isolation to groups has the reduced blood level of corticosteroid, and the
      control rats has an increased one. According to our opinion, under the conditions
      of low population density the prenatal stressed animals show better adaptive
      reaction because the estrous cycle reduction and the estrus phase prolongation
      make the possibility of pregnancy higher.

PMID- 20795478
TI  - [Contribution of glucocorticoid hormones to gastroprotective effect of ischemic
      preconditioning in rats with normal and deficient prostaglandin production].
AB  - The study was designed to investigate whether glucocorticoid hormones participate
      in gastroprotective effects of ischemic preconditioning in rats with normal and
      deficient prostaglandin production. To estimate the role of glucocorticoids
      adrenalectomy followed by appropriate corticosterone replacement and inhibition
      of corticosterone synthesis by metyrapone were used. Prostaglandin synthesis was
      inhibited by indomethacin. In control rats gastric ischemic preconditioning (a
      0.5 h ischemia-reperfusion) induced plasma corticosterone rise and attenuated
      gastric injury caused by 3.5 h ischemia-reperfusion. The gastroprotective effect
      of ischemic preconditioning was prevented by adrenalectomy as well as metyrapone
      pretreatment in both groups, in the rats with normal and deficient prostaglandin
      production. Acute corticosterone replacement to adrenalectomized rats during
      ischemic preconditioning restored the protective effect of ischemic
      preconditioning on the gastric mucosa even in the rats with inhibited
      prostaglandin synthesis. Thus, the glucocorticoid hormones were shown to
      contribute to gastroprotective effect of ischemic preconditioning in the rats
      with normal and deficient prostaglandin production.

PMID- 20795479
TI  - [Changes in the uterus morphometric parameters in prenatally stressed rats].
AB  - The effects of immobilization stress from 15th to 18th days of gestation on
      morphometric parameters of the adult offspring uterus were studied. The results
      showed that there were no changes of endometrial morphometry in respect to
      oestrous cycle in 3-month prenatally stressed female. Prenatal stress decreased
      the myometrium thickness in oestrus and diestrous owing to circular muscle layer.
      These data suggested that influence of prenatal stress on morphometric parameters
      of the rat uterus was induced by disturbance of sex steroid secretion.

PMID- 20795481
TI  - [The miniature system of independent micromanipulators for recording the neuronal
      activity in unrestrained animals].

PMID- 20795480
TI  - [Glucose absorption from mono- and oligosaccharide solutions in the rat small
      intestine in vivo].
AB  - The rates of maltose and maltotriose hydrolysis, and glucose absorption in the
      isolated loop of the rat small intestine, perfused by isocaloric solutions of the
      above substrates, were examined in chronic experiments. In all the experiments,
      the rates of glucose absorption from the solutions of maltose and maltotriose (M-
      and MT-glucose, respectively) were almost the same as those from the isocaloric
      solutions of free glucose (G-glucose). The rate of water absorption in the
      isolated intestinal loop was significantly higher under the perfusion with
      maltose (100 mM) and maltotriose (66.6 mM) solutions than under the perfusion
      with equivalent glucose solutions. The results of mathematical simulation, in
      which absorptive surface of the small intestine was approximated as a folded
      surface with an adjoining zone of diffusion, were in a good agreement with the
      experimental data. The model showed that in the range of physiological
      concentrations of the substrates their transfer across the pre-epithelial layer
      by water flux seemed to play a minor role as compared with a transfer by
      diffusion. According the results obtained, the most significant factors that
      influence the efficiency of coupling between hydrolysis and absorption of
      nutrients, are following: a complex geometry of intestinal surface, the pre
      epithelial diffusion layer, the rate of water absorption (secretion) in the
      intestine.

PMID- 20795482
TI  - [Laboratory for study of an actor's creative activity at the Russian Theatre
      Society].

PMID- 20795483
TI  - [Detection of Borrelia miyamotoi in ticks Ixodes persulcatus from Russia].
AB  - Unfed adult Ixodes persulcatus ticks from five regions of Russia were examined to
      analyze the distribution and diversity of Borrelia miyamotoi. DNA of B. miyamotoi
      was found in 1.8% of ticks from Leningrad Oblast, 2.9% from Sverdlovsk, 4.5% from
      Novosibirsk, 2.3% from Irkutsk Oblast, and 2.5% from Khabarovsk Krai. The
      molecular typing of the B. miyamotoi DNA was based on the partial sequencing of
      the 16S rRNA, p66, and glpQ genes. The only genetic variant of B. miyamotoi was
      detected in all samples of ticks collected from these five territories.

PMID- 20795484
TI  - [A new blackfly species Montisimulium birzhankolum Yankovsky, Isakaev et
      Khasanova, sp. n. (Diptera: Simuliidae) from northeastern Kazakhstan].
AB  - A new species of blackflies, Montisimulium birzhankolum Yankovsky, Isakaev et
      Khasanova, sp. n., is described from male, female, and pupa specimens collected
      in Pavlodar Province of Northeastern Kazakhstan. The new species differs from all
      other species of the genus Montisimulium by morphology of pupal gills.

PMID- 20795485
TI  - [Microevolutionary aspects of morphological variability and specificity of
      cestodes by the example of Proteocephalus longicollis (Zeder, 1800)
      (Proteocephalidae), a parasite of Coregonids].
AB  - Morphological variability of the cestode Proteocephalus longicollis from the
      smelt Osmerus eperlanus L., which was spontaneously introduced into the Syamozero
      Lake, has been studied. It was established that P. longicollis became an abundant
      element of the smelt parasite fauna during last 20 years, thereby showing the
      absence of host specificity. It was revealed that morphological polymorphism of
      P. longicollis from smelt combines features of ecological forms characteristic
      for aboriginal host species, namely whitefish Coregonus lavaretus L. and vendace
      Coregonus albula L. Cestodes from smelt are more similar to ecological forms from
      whitefish by the characteristics of variability. It is concluded that
      colonization of a host species, which is new for a given water body, is
      accompanied by the forming of a new group of host, which contributes to the
      maintenance of the parasite number and to its population stability under changing
      conditions of freshwater ecosystems.

PMID- 20795486
TI  - [On the conspecificity of Ostertagia ostertagi and Ostertagia lyrata (Nematoda:
      Ostertagiinae)].
AB  - Partial sequences of the second internal transcribed spacer (ITS-2) rDNA were
      obtained for Ostertagia ostertagi and O. lyrata, which are supposedly constitute
      two morphologically distinct variants of the species. The 1.4% level of
      difference between the ITS-2 sequences of O. ostertagi and O. lyrata was
      reported, whereas the sequences derived from worms of the same morph were
      completely identical. The data obtained prevent an attribution of O. ostertagi
      and O. lyrata to the same species.

PMID- 20795488
TI  - [Development of monogeneans from the family Tetraonchidae under experimental
      conditions].
AB  - Experimental data on the development of the Tetraonchus borealis larvae and
      species of the genus Salmonchus are given for the first time. The experiments was
      carried out in field conditions, in the estuary of the Shegnanda river (Baikal
      Lake basin), during 25 days. It was established that temperatures from 15 to 22
      degrees C are favorable for the culture of the Salmonchus eggs followed by the
      emergence of larvae at eighth or ninth day. At the same time, T. borealis larvae
      need in lower temperatures, from 15 to 17 degrees C for their development.
      Detailed descriptions of eggs and larvae of the Tetraonchidae species under are
      given.

PMID- 20795487
TI  - [Soricinia sawadai sp. n. (Cyclophyllidea: Hymenolepididae), a new cestode
      species from the shrews of Sakhalin Island].
AB  - A new species Soricinia sawadai sp. n. parasitizing shrews of Sakhalin Island
      (Sores unguiculatus and S. caecutiens) is described. The new species differs from
      other species of the genus Soricinia Spassky et Spasskaja, 1954 in having
      specific armament and size of the cirrus. Soricinia sawadai sp. n. differs from
      S. aurita (Irzhavsky et al., 2005) in having half size of the ovary (0.076-0.08 x
      0.03-0.038 versus 0.135-0.14 x 0.037-0.04) and the cirrus bursa extending into
      the aporal fraction of the middle part of segment. The new species differs from
      S. quarta (Karpenko, 1983) in having half size of the cirrus (0.025-0.026 versus
      0.05-0.055) and half number of hexacants in uterine segments (20-22 versus 40
      45). The new species differs from S. infirma (Zarnowski, 1955) in having other
      cirrus armament, larger number of segments and lesser number of hexacants. The
      species Insectivorolepis macracetobulosa Sawada et Koyasu, 1991 parasitizing
      Sorex unguiculatus on Hokkaido Island is synonymized with Soricinia quarta. The
      species Insectivorolepis macracetobulosa sensu Sawada et Harada, 1993
      parasitizing Sorex shinto shinto on Honshu Island is described as a separate
      species Soricinia haradai sp. n.

PMID- 20795489
TI  - [Muscular system of the Microphallus pygmaeus metacercaria (Trematoda:
      microphallidae)].
AB  - The musculature of body wall, attachment organs (oral and ventral suckers), and
      internal organs (alimentary tract, excretory bladder, and ducts of reproductive
      system) of the Microphallus pygmaeus metacercaria are described. An unusual
      arrangement of longitude and diagonal muscles was found in the hind part of the
      metacercaria body. Longitude fibers of dorsal and lateral body surfaces are bow
      shaped and bend round the excretory pore along its ventral margin. An additional
      group of diagonal fibers is situated in the hind part of ventral body surface.

PMID- 20795490
TI  - [Modern state of knowledge on the life cycles in Myxozoa].
AB  - A critical review of modern studies on the life cycles of Myxozoa is presented.
      List of myxosporidian species with known life cycles is given.

PMID- 20795491
TI  - [Intergenomic chromosome substitutions in wheat interspecific hybrids and their
      use in the development of a genetic nomenclature of Triticum timopheevii
      chromosomes].
AB  - The results of analysis of the genome formation in interspecific hybrids of
      Triticum aestivum with T. timopheevii are reviewed. The spectra of substitutions
      and rearrangements are shown to depend on the genotypes of the parental forms and
      on the direction of selection. The frequencies of substitutions of individual T.
      timopheevii chromosomes significantly vary and reflect the level of their
      divergence relative to the common wheat chromosomes. Some aspects of
      classification of the A(t)- and G-genome chromosomes are discussed.

PMID- 20795492
TI  - [Inversion polymorphism of Glyptotendipes glaucus Mg. (Diptera: Chironomidae)
      from the reservoirs of Kaliningrad].
AB  - The karyotypes of larvae Glyptotendipes glaucus Mg. 1804 from three reservoirs of
      Kaliningrad city (Pen'kovoe and Karasevka lakes and Chistyi pond) were studied.
      The levels of the natural inversion polymorphism for the three populations were
      determined. Ten new inversion sequences (gla B4, gla B5, gla B6, gla D5, gla E4,
      gla E6, gla E7, gla F6, and gla F7) were detected in the species studied.
      Inversion including the centromeric region in IIIEF (gla E6 + gla F7) was
      pericentric. Several cases ofgla B5 and gla B6 combination with gla B2 resulting
      in genotypic combination gla B2.5 and gla B2.6 were found. The dependence of the
      number of inversion sequences and genotype combinations from the content of heavy
      metal ions in sediments of the reservoirs was revealed. All populations were
      characterized by the prevalence of inversion sequence gla B2 in chromosome I.

PMID- 20795493
TI  - [Diversity of genes encoding nonribosomal peptide synthetases in the Streptomyces
      sioyaensis genome].
AB  - Streptomyces sioyaensis Lv81 produces siomycin, a thiopeptide antibiotic
      synthesized on ribosomes. Nothing is known about the ability of this strain to
      produce nonribosomal peptides, a well represented group of natural actinomycete
      compounds. Using degenerate primers, we cloned a number of DNA fragments encoding
      putative adenylation domains (A domains) of nonribisomal peptide synthetases
      involved in biosynthesis of unknown compounds. Sequencing of amplicons revealed
      nine different A domains, which were analyzed in more detail. Nonribosomal codes
      of these domains were determined, but in most cases their substrate specificity
      failed to be unambiguously predicted. This means that many of these domains can
      recognize novel amino acids and be used to improve and expand the bioinformatic
      toolbox applied to predict substrate specificity of A domains. Multiple sequence
      alingments showed that the cloned A domains are probably involved in different
      biosynthetic pathways. Five A domains were used in gene inactivation experiments.
      Inactivation of one of them (in strain 736) resulted in a decrease of the total
      antibiotic activity as compared to the initial strain. Other A-domain mutants
      were similar to the initial strain in morphology and siomycin production. The
      causes of reduced antibiotic activity of strain 736 are discussed.

PMID- 20795494
TI  - [Localization of denitrification genes in plasmid DNA of bacteria Azospirillum
      brasilense].
AB  - In 85-Mda plasmid (p85) of plant-associated bacteria Azospirillum brasilense
      Sp245 model strain, the genes encoding copper-containing nitrite reductase
      (nirK); heterodimeric NO-reductase (norCB); NorQ and NorD proteins affecting
      synthesis and (or) activation of NirK and (or) NO-reductase (norQD); catalytic
      subunit I ofcytochrom c oxidase (CccoN); presumable NO sensor carrying two
      hemeerythrine domains (orf181); and an enzyme required for synthesis of
      presumable NO antagonist, homocystein (metC) were identified. In the same region
      of p85, orf293 encoding transcriptional regulator of LysR type, orf208 whose
      protein product carries a formylmethanofuran dehydrogenase subunit E domain, and
      an orf164-encoding conservative secretory protein with unknown function were also
      found. Localization of a set of denitrification genes in the plasmid DNA A.
      brasilense Sp245 adjacent to IS elements ISAzba1 and ISAzba2 indicates potential
      mobility of these genes and high probability of their horizontal transfer among
      populations of rhizospheric bacteria. A site homologous to p85 nirK-orf208-orf181
      genes was detected in the 115 kb plasmid of A. brasilense Sp7 type strain.

PMID- 20795495
TI  - [Genetic variation in a sorghum line with multiple genetic instability induced
      with ethidium bromide in an in vitro culture].
AB  - Ethidium bromide treatment (15 mg/l, 26 degrees C, 18 h) of a sorghum
      Zheltozernoe 10 callus culture yielded line Zh10-brl displaying multiple genetic
      instability. The line was characterized by a broad variety of mutations, which
      were identified in consecutive generations obtained from one initial regenerant
      via self-pollination. The mutation caused male sterility (male sterility,
      generation R1), a low plant height (dwarfness, R2), a reduced awn length
      (awnless, R3), yellow leaves in seedlings (xantha, R6), leaf variegation (leaf
      variegation, R6), leaf bleaching (virescence, R6), etc. In some cases,
      segregation in families suggested a monogenic recessive inheritance for the
      induced mutations. Male sterility was due to a range of defects that affected
      microsporogenesis and microgametogenesis and were probably caused by mutations of
      several genes. Leaf variegation was due to the appearance of green areas in
      originally albino seedling leaves; the reversion occurred only in somatic tissues
      without affecting male and female gametes. In male-sterile and variegated
      mutants, sequence-specific amplified polymorphism (SSAP) analysis with primers to
      the Isaak transposon revealed new DNA fragments, which were absent from the
      original line. The results supported the hypothesis that the mutations isolated
      in line Zh10-brl result from transposon mobilization induced by ethidium bromide
      and/or in vitro culture conditions.

PMID- 20795496
TI  - Evaluation of genetic variability in choosen apple (Malus x domestica Borkh.)
      cultivars by ISSR-PCR analysis.
AB  - The aim of the study was to determine the genetic variability in eight apple
      cultivars: Delikates, Cortland, James Grieve, Lired, Jonathan, Golden Delicious,
      Jonagold and Idared from the collection of Fruit Growing Research Station in
      Rajkowo of the West Pomeranian University of Technology, Szczecin. The cultivar
      Delikates was obtained from the crossing of two cultivars: Cortland and James
      Grieve, whereas cultivar Lired is a James Grieve's sport. The second one cultivar
      -Jonagold was obtained from the crossing of Jonathan and Golden Delicious. The
      cultivar Idared is a hybrid obtained from the crossing of Jonathan and Wagener.
      Out of 40 primers, 17 were chosen for the final study. Those amplified a total of
      183 loci (872 amplicons) out of which 34 (18.5%) were monomorphic, 128 (69.5%)
      were polymorphic and 22 (12%) cultivar-specific. Specific ISSR products were
      detected for each apple cultivar. A dendrogram was constructed using the UPGMA
      method which revealed two distinct clusters: I--Delikates, Cortland, James Grieve
      and Lired, II--Jonathan, Golden Delicious, Jonagold and Idared. Genetic
      similarity between Delikates, Cortland and James Grieve was 68.6, 70.8%,
      respectively and between cultivar Jonagold, Jonathan and Golden Delicous was
      79.8, 85.2%, respectively.

PMID- 20795497
TI  - Gene ontology study of methyl jasmonate-treated and non-treated hairy roots of
      Panax ginseng to identify genes involved in secondary metabolic pathway.
AB  - The roots of Panax ginseng C.A. Meyer, known as Korean ginseng have been a
      valuable and important folk medicine in East Asian countries. It mainly used to
      maintain the homeostasis of the human body, with the presence ofginsenosides and
      non-saponin compounds like phenol compounds, acidic polysaccharides and
      polyethylene compounds. Functional genomics aid to annotate based on gene
      ontology. In this study, we focused on the genes involving in secondary metabolic
      pathways and to visualize temporal changes of gene expression in ginseng hairy
      roots with methyl ester methyl jasmonate (MeJA) along with non-treated hairy
      roots. A 5.774 EST clones were clustered and assembled as 501 contigs and 2.955
      singletons. Annotations categorized with molecular functions, biological
      processes, cellular compounds of gene ontological terms and biochemical
      functions, enzyme commission to sequences were assigned to metabolic pathways of
      Kyoto Encyclopedia of Genes and Genomes database. Comparatively, EST sequences
      are assigned to cellular process, metabolic process, biotic and abiotic stress
      stimuli, developmental and biological regulations and transports are up-regulated
      2-3 fold in MeJA treated hairy roots. 46 different sub groups of enzymes found in
      the MeJA treated plants. These annotated ESTs represents a significant proportion
      of the P. ginseng and provides molecular resource for developmental of
      microarrays for gene expression studies concerning development, metabolism and
      reproduction.

PMID- 20795498
TI  - The structure of sterile cytoplasm types within a maize genebank collection.
AB  - Maize Research Institute (MRI) gene bank maintains a collection of 6000 maize
      accessions. Within this collection over 100 sources of cytoplasmic male sterility
      (CMS) were found in field trials, i.e. more than 2% of the total accession
      numbers. These sources are distributed among Yugoslav open-pollinated varieties
      (4.56% of them contain CMS), as well as introduced heterozygous genotypes and
      inbred lines. In order to identify cytoplasm types the gene-bank sources of CMS
      were screened using a PCR assay with specific primers for C, T and S cytoplasms.
      Predominant cytoplasmic male sterility type among the analyzed accessions was CMS
      S. Results were inconclusive for three accessions, i.e. different results for the
      progenies of two ears per accession were obtained. For another two accessions a
      new PCR product profile was identified, consisting of one band characteristic for
      CMS-S and one unspecific for any of the three CMS types. The PCR approach enabled
      a simple, fast and reliable large scale screening of maize cytoplasm among MRI
      gene bank accessions, significantly reducing time for cytoplasm characterizations
      compared to classical method of testing with restorers for each known type of
      CMS.

PMID- 20795499
TI  - [RAPD analysis of the intraspecific and interspecific variation and phylogenetic
      relationships of Aegilops L. species with the U genome].
AB  - RAPD analysis was used to study the genetic variation and phylogenetic
      relationships of polyploid Aegilops species with the U genome. In total, 115 DNA
      samples of eight polyploid species containing the U genome and the diploid
      species Ae. umbellulata (U) were examined. Substantial interspecific polymorphism
      was observed for the majority of the polyploid species with the U genome
      (interspecific differences, 0.01-0,2; proportion of polymorphic loci, 56.6
      88.2%). Aegilops triuncialis was identified as the only alloploid species with
      low interspecific polymorphism (interspecific differences, 0-0.01, P = 50%) in
      the U-genome group. The U-genome Aegilops species proved to be separated from
      other species of the genus. The phylogenetic relationships were established for
      the U-genome species. The greatest separation within the U-genome group was
      observed for the US-genome species Ae. kotschyi and Ae. variabilis. The
      tetraploid species Ae. triaristata and Ae. columnaris, which had the UX genome,
      and the hexaploid species Ae. recta (UXN) were found to be related to each other
      and separate from the UM-genome species. A similarity was observed between the U
      M-genome species Ae. ovata and Ae. biuncialis, which had the UM genome, and the
      ancestral diploid U-genome species Ae. umbellulata. The UC-genome species Ae.
      triuncialis was rather separate and slightly similar to the UX-genome species.

PMID- 20795500
TI  - [Molecular genetic analysis of the two morphs of sea star shrimp Periclimemes
      soror Nobili, 1904, the symbionts of tropic sea stars].
AB  - Two morphologically similar morphs of the Periclimemes soror shrimps were
      subjected to nucleotide sequence analysis of the mitochondrial COI gene fragment
      and highly variable nuclear fragment, D1/D2 domain of the large subunit of their
      ribosomal RNA genes. These shrimps are widely distributed in the Indo-West
      Pacific and are obligate symbionts of sea stars. The morphs are different in
      color patterns, as well as in specific reaction relative to their hosts. The
      nucleotide sequence data obtained revealed no differentiation relative to the
      fragments examined.

PMID- 20795501
TI  - [Erratic divergent evolution in fish from the Northern Pacific].
AB  - The mtDNA divergence was examined in some families of anadromous and semi
      anadromous fish. Heterogeneous distribution of the divergence values along the
      scale was demonstrated. Statistically significantly higher number of the species
      pairs were characterized by divergence values ranging from 2 to 4% and 5 to 12%
      of nucleotide substitutions. These results suggest that in different monophyletic
      groups occupying common historical ranges, divergence-associated speciation often
      happened within similar time intervals. Comparison of the species divergence time
      calculated using the molecular clock pointed to the coincidence of the radiation
      periods in the taxa with paleogeological and paleoclimatic global changes in the
      history of Northern Pacific.

PMID- 20795502
TI  - [Incomplete congruence between morphobiological characters and sex-specific
      molecular markers in Pacific salmons: 1. Analysis of discrepancy in five species
      of the genus Oncorhynchus].
AB  - The congruence between molecular markers, identifying the presence of the Y
      chromosome, and secondary sexual characters was examined in Asian populations of
      five Pacific salmon species: pink salmon (Oncorhynchus gorbuscha), chum salmon
      (O. keta), sockeye salmon (O. nerka), chinook salmon (O. tschawytsha), and sima
      (O. masou). It was demonstrated that in all species examined, the presence or
      absence of sex-specific molecular markers was to a considerable degree congruent
      with secondary sexual characters, but in some cases, an incongruence was found.
      These findings suggested that the mechanism underlying this phenomenon was
      similar or identical in all species examined. Possible genetic and physiological
      explanations of this phenomenon are discussed.

PMID- 20795503
TI  - [Polymorphism of the cox1 gene in bird schistosome cercaria isolates (Trematoda,
      Schistosomatidae) from ponds of Moscow and Moscow oblast].
AB  - Polymorphism of a 8 10-bp mitochondrial cox1 gene region was studied in 16
      cercaria isolates of bird schistosomes (family Schistosomatidae), which were
      collected in water bodies of Moscow and Moscow oblast and represented three
      species: Trichobilharzia szidati, T. franki, and T. regenti. A substantial
      predominance of AT (65.4%) was characteristic of the cox1 sequences in all three
      species. Rare single nucleotide substitutions determined low (0.2-0.9%)
      intraspecific nucleotide and amino acid sequence diversity. Haplotype diversity h
      was high (80-100%) in all three species, suggesting a unique character for almost
      all cox1 sequences in the sample. Phylogenetic trees based on the nucleotide and
      amino acid sequence variations were constructed to study the relationships of the
      three schistosome species. A high support was observed for the main branching
      node that reflects differentiation of the monophyletic group Trichobilharzia and
      species of the genera Bilharziella (B. polonica), Dendritobilharzia (D.
      pulverulenta), and Gigantobilharzia (G. huronensis). Based on the nucleotide
      substitutions and amino acid polymorphisms, two groups of isolates, which infect
      Lymnaea stagnalis (T. szidati) and snails of the group Radix (T. franki and T.
      regenti) respectively, were isolated in the genus Trichobilharzia. The time of
      divergence between the two schistosome groups infecting snails of the genera
      Radix and Lymnaea was calculated from the cox1 nucleotide substitution rate,
      which is known for Asian and Indian blood flukes from the genus Schistosoma and
      is 2-3% per million years on average. Divergence of the three bird schistosome
      species under study and divergence of the Asian species of mammalian schistosome
      were almost concurrent, dating back to 2.5-3.8 Myr ago. Factors responsible for
      the lack of intraspecific subdivision with respect to the cox1 gene in bird
      schistosomes and the lack of separation between two species (T. franki and T.
      regenti) are discussed.

PMID- 20795504
TI  - [Simulation of the distribution of spinocerebellar ataxia type 1 in Yakut
      populations: model parameters and results of simulation].
AB  - Demographic and clinical genetic parameters used for simulation modeling of the
      prevalence of spinocerebellar ataxia type 1 (SCA1) in Yakut populations are
      described. Demographic parameters of simulated populations and the clinical
      genetic characteristics of carriers of the SCA1 mutant allele in them have been
      compared with actual data on Abyisky and Ust-Aldansky uluses of the Republic of
      Sakha (Yakutia). The results of a series of simulation experiments (without
      migration or spontaneous mutagenesis) agree with the conclusion that the high
      prevalence of rate of spinocerebellar ataxia type 1 in Yakut populations may be
      maintained because of their specific demographic structure. Prediction of the
      disease prevalence has shown that it will take about 1290 years for natural
      selection to eliminate the mutation from the population. If medical genetic
      counseling (MGC) is offered to 1% of the carriers of the mutation, this period
      will be reduced to 200 years.

PMID- 20795506
TI  - [Analysis of microsatellite DNA of rainbow trout (Parasalmo (Oncorhynchus)
      mykiss) of Kamchatka: selection of loci and optimization of the method].
AB  - The variation of a sample of rainbow trout (Parasalmo (Oncorhynchus) mykiss) from
      natural populations of several rivers of the Kamchatka Peninsula with respect to
      43 microsatellite DNA loci has been studied. These loci were earlier used for
      analysis of Asian populations of closely related salmonids. Ten of them may be
      regarded as markers and seen promising for further studies on intraspecific
      relationships of rainbow trout of Kamchatka. Their use in studies on more
      numerous samples from different localities and populations of Parasalmo (O.)
      mykiss in the Asian part of the species range will ensure efficient population
      genetic analysis of the Kamchatka population group of this species.

PMID- 20795505
TI  - [Tobacco transformants expressing the Medicago truncatula ornithine
      aminotransferase cDNA].
AB  - The Medicago truncatula ornithine aminotransferase cDNA was cloned under the
      potent constitutive 35S RNA promoter of the cauliflower mosaic virus and
      transferred into the genome of tobacco Nicotiana tabacum SR1 plants. Transformed
      tobacco plants grew better in salinity stress, but did not differ in proline
      content under normal or stress conditions from control plants. It was assumed
      that the role of ornithine aminotransferase in the molecular mechanisms of stress
      resistance is not associated with additional proline synthesis.

PMID- 20795507
TI  - Medical case reports: a modern tradition.

PMID- 20795508
TI  - The changing face of hepatitis B in greater Glasgow: epidemiological trends 1993
      2007.
AB  - BACKGROUND AND AIMS: Whilst hepatitis B (HBV) is historically uncommon in
      Scotland, anecdotal experience suggests an increasing prevalence of chronic
      infection. We sought to establish whether the incidence of chronic HBV is
      increasing in Greater Glasgow, and whether patients are assessed in secondary
      care. METHODS: The regional virus centre database identified HBV surface antigen
      (HBsAg) positive samples. For adult patients tested in Glasgow between 1993-2007
      the first positive test was identified and classified as acute or chronic
      infection serologically. Clinic referral and attendance data was then obtained.
      RESULTS: 1,672 patients tested HBsAg positive; 1051 with chronic infection, 421
      acute and 200 indeterminate. New diagnoses of HBV remained stable over time,
      however falling numbers of acute cases were mirrored by a rise in chronic cases
      from 40 to 119 per annum between 2000 and 2007. Of 193 patients diagnosed in 2006
      and 2007, 51% were not seen in secondary care due to non referral (43%) or non
      attendance (8%). CONCLUSION: Chronic HBV trebled in Glasgow between 2000 and
      2007. Most patients were not assessed in secondary care. Improved levels of
      clinic referral and attendance are required to ensure best care for HBV patients
      in Glasgow.

PMID- 20795509
TI  - Scottish survey of public place defibrillators.
AB  - BACKGROUND: Public place defibrillators can reduce delays to defibrillation but
      their cost-effectiveness has not been evaluated in randomised trials. In
      Scotland, unlike England, no health sector funding has been provided.
      Nonetheless, anecdotal evidence suggests they are increasing in number. METHODS:
      A cross-sectional survey was conducted of all airports, shopping malls, leisure
      centres, and major train and bus stations to determine whether defibrillators had
      been purchased and by whom, the training and maintenance arrangements, and
      whether they had been discharged. RESULTS: Of the 183 eligible sites, 153 (84%)
      participated. 33 (22%) had at least one defibrillator. Those in airports and
      shopping malls were purchased privately. Those in leisure centres were bought by
      charities or local authorities. The majority (97%) provided training to existing
      staff, but 6 (18%) provided no training to new staff. Only 6 (18%) had a
      maintenance agreement and 8 (24%) a replacement policy. Only one site permitted
      public access. Defibrillators had been discharged in 10 (30%) sites. Of the 32
      people shocked, 23 (72%) survived until the ambulance arrived. CONCLUSIONS:
      Despite absence of health sector funding, defibrillators are located in 22% of
      high footfall public places. Those purchasing defibrillators need to ensure
      adequate maintenance, replacement and training arrangements.

PMID- 20795510
TI  - Survey of anaphylaxis management by general practitioners in Scotland.
AB  - AIM: To obtain a snapshot of how patients with potentially life-threatening
      allergies are managed within a Primary Care setting. METHODOLOGY: A questionnaire
      based survey sent to all General Practitioners in Scotland. RESULTS: Six hundred
      and thirteen replies were suitable for analysis. Ninety percent of respondents
      had prescribed adrenaline auto-injector pens, almost exclusively the EpiPen
      device. Less than half were personally confident in their use and only 17% had
      access to a dummy trainer pen for demonstration purposes. Twenty seven percent
      would prescribe one auto-injector only. Six percent reported accidental mis
      firing of adrenaline pens, although with no serious sequelae. Refusal of pens by
      patients was noted by 1%. In the event of an anaphylactic emergency, 90% of
      respondents would use adrenaline as first-line treatment, although only half
      would use the UK Resuscitation Council recommended adult dose of 0.5mg by the
      intramuscular route (or 0.3mg by auto-injector). Eleven percent would give
      adrenaline by the slower subcutaneous route and 3% by the intravenous route.
      Thirty six percent had themselves treated such a case outside of hospital. Sixty
      two percent of respondents would seek specialist investigation of anaphylaxis,
      although only 31% felt that ready access was available. Frequent concerns were
      raised about current provision of care for patients with allergic disease and
      their own ability to deal with this. CONCLUSION: Investment is required, both to
      provide basic training and ongoing support for Primary healthcare staff in the
      management of allergic disease, and also for necessary accompanying specialist
      support.

PMID- 20795511
TI  - Scottish Stroke Research Network: the first three years.
AB  - Research networks were introduced in the UK to facilitate and improve clinical
      research and stroke was seen as a priority topic for local research network
      development. The Scottish Stroke Research Network (SSRN) is one of 11 stroke
      research networks in the UK. In this article we review the progress of the
      Scottish Stroke Research Network in the three years since inception. Between 2006
      2009 the number of active hospital research sites has increased from 10 to 22
      expanding to involve 20 stroke research nurses. There was a corresponding 58%
      increase in recruitment of participants into stroke studies, from 376 in 2006/07
      to 594 in 2008/09. The majority (17/20) of our current studies are
      interventional. Data from one of these, the CLOTs trial (Clots in Legs Or
      sTocking after Stroke), demonstrates that the annual recruitment in Scotland
      increased from a median of 94 (range 6-122) patients per year in the six years
      before the SSRN, to 140 (135-158) patients per year after SSRN involvement. We
      currently screen about 50% of Scottish stroke patients and approximately 5% of
      Scottish stroke patients are participating in research studies that we support.
      The SSRN has made good progress in the first three years. Increasing the
      recruitment of screened patients remains a challenge.

PMID- 20795512
TI  - Equality of access to "fast-track" stroke services in an older, socio
      economically deprived Scottish population.
AB  - BACKGROUND AND AIMS: Unequal access to specialist stroke services may contribute
      to the disproportionate stroke burden in certain populations. We evaluated the
      relationship between access to TIA services, deprivation and age. METHODS: We
      prospectively recorded referral pattern data on consecutive TIA service patients.
      Socio-economic deprivation was derived from postcode and census data.
      Associations were described using Kruskal-Wallis statistics. RESULTS: Of 3,462
      patients assessed, there was no association between time to clinic referral or
      attendance and increasing deprivation or age. CONCLUSION: Inequality of access to
      TIA services for older, deprived patients was not evident. However, delay to
      assessment and prevalence of risk factors was substantial for all patients.

PMID- 20795513
TI  - Crohn's disease incidence in NHS Tayside.
AB  - BACKGROUND & AIMS: The incidence of Crohn's disease (CD) in northeastern Scotland
      was last reported as rising in the 1980's, while in the rest of Europe it had
      reached steady state. This study reviewed the incidence of CD in NHS Tayside.
      METHODS: Data was collected retrospectively and analysed using age and sex
      standardization, socioeconomic factors and urban and rural postcodes. RESULTS: A
      point prevalence of 157 per 100,000 population in the Tayside region was found.
      The average incidence of CD was 9.56 per 100,000 per year between 2003 and 2007
      and 7.16 per 100,000 per year between 1998 and 2001. There was no link to
      urbanization and no difference in incidence between the sexes. Incidence was not
      related to affluence in this population and peak age of onset occurred in the
      third decade of life only. 12.7% of patients had a family history of inflammatory
      bowel disease and 25% of patients were current smokers. CONCLUSIONS: The
      incidence of CD appears to have arrived at a steady state in Tayside, while
      recent evidence suggests that it is on the rise in Scandinavia again. The results
      of the genetic studies to come from the east of Scotland are eagerly awaited to
      help shed light on the aetiology of this complex disorder.

PMID- 20795514
TI  - Obstetric care of new European migrants in Scotland: an audit of antenatal care,
      obstetric outcomes and communication.
AB  - BACKGROUND AND AIMS: There has been a twelve-fold increase in the number of New
      European migrants giving birth in Lothian between 2004 and 2007. The objective of
      this study was to audit obstetric care standards in Lothian for new migrants and
      recommend service improvements. METHODS: A retrospective audit of 114/136 (84%)
      obstetric case records of new European migrants giving birth in Lothian hospitals
      in 2006 was conducted. Assessment was against care standards for antenatal
      booking, antenatal attendance and interpretation. Obstetric outcomes were audited
      against the general population. RESULTS: Eighty percent were primiparous. Fifty
      five percent had booked by the end of week 14. Mean birth weights and lengths of
      stay were similar to the general population. Intervention rates were 23% for
      Caesarean Sections (C/S) and 17% for instrumental deliveries (versus 27% and 19%
      respectively in the general population). Epidural or spinal anaesthesia was used
      for 57% compared to 50% of the general population. The interpretation services
      (ITS) were used infrequently. CONCLUSIONS: Full compliance with antenatal and
      interpretation standards was not achieved for this population. ITS was most
      commonly used to meet the needs of healthcare professionals, rather than as a
      routine. While there were no significant differences in maternity outcomes, poor
      communication did affect care.

PMID- 20795515
TI  - Current practice of obtaining informed consent for local steroid injection among
      the shoulder and elbow surgeons in United Kingdom.
AB  - BACKGROUND: Local steroid injection is a common procedure and not without risks.
      AIM: To establish the current practice of obtaining informed consent for local
      steroid injection among shoulder and elbow surgeons in the UK. METHODS: A postal
      questionnaire survey was distributed to 176 orthopaedics surgeons in UK who were
      members of the British Elbow and Shoulder Society. RESULTS: 68% of the surgeons
      considered local steroid injection invasive. 88% of the surgeons obtained verbal
      consent only. Of these, only 19% recorded the discussion. Almost all the surgeons
      (96%) explained the desired effects and 26% provided statistical evidence of
      local steroid injection. About 88% of the surgeons mentioned other drugs included
      in the injection. Only 13% of them mentioned the dose of the steroid used. 82%
      and 77% of the surgeons offered alternative treatment options and the right to
      refuse injection respectively. 85% and 59% of the surgeons discussed local and
      systemic risks of steroid injection, respectively. The most common risk mentioned
      by the surgeons is short term increase of pain. CONCLUSIONS: Majority of the
      surgeons used verbal consent only for local steroid injection. The consent
      discussion was not regularly documented in case notes and the information
      delivered varies.

PMID- 20795517
TI  - Surgery for faecal incontinence.

PMID- 20795516
TI  - Titanium intramedullary nailing for treatment of simple bone cysts of the long
      bones in children.
AB  - BACKGROUND: Simple or unicameral bone cysts are common benign fluid-filled
      lesions usually located in the long bones of children before skeletal maturity.
      Pathological fracture is common, and is often the presenting feature. AIM: The
      objective of the present study was to evaluate the results of titanium
      intramedullary nailing for the treatment of unicameral bone cysts with or without
      a pathological fracture. METHODS: During the period 2001 to 2007, flexible
      intramedullary nailing for the treatment of a unicameral bone cyst was performed
      in 18 children. Four of these patients presented with a pathological fracture.
      The cyst was located in the humerus in 14 patients, in the femur in three, and in
      the tibia in one. The diagnosis was based on typical radiographs and computed
      tomography. The mean age of the patients at the time of surgery was 9.4 years,
      and the mean duration of follow-up was 53 months. Radiographic evaluation was
      performed, and the cyst was classified as completely healed, healed with residual
      radiolucency, recurred, or having no response. RESULTS: Mean hospital stay was 24
      hours. At one to four weeks postoperatively, all patients were pain free and had
      full range of motion of adjacent joints. Radiographic signs of cyst healing were
      present at three months in all patients, and all cysts healed completely. All of
      the cysts responded to treatment, with no cyst recurrence. No major complications
      were observed. CONCLUSION: Elastic intramedullary nailing has the twofold
      benefits of continuous cyst decompression, and early immediate stability to the
      involved bone segment, which permits early mobilization and return to normal
      activities.

PMID- 20795518
TI  - Aberdeen's plague epidemic of 1647-48.
AB  - This article discusses the plague epidemic that broke out in Scotland in the mid
      1640s, particularly its effects on the city of Aberdeen where it remained
      virulent from April 1647 until the end of the following year. Prevailing medical
      understandings of disease causation and transmission will be discussed, and it
      will be shown that governments attempted to restrict outbreaks in accordance with
      these beliefs. The spread of plague throughout Scotland from 1644 will be
      summarised, with the focus on the impact of the disease on Aberdeen in 1647-48.
      The surviving council registers and other primary sources will be used to show
      how the city's governors responded to the dual threat of miasma and contagion in
      well-established ways.

PMID- 20795519
TI  - [Disorder specific therapy of structural disorders in adolescents].

PMID- 20795520
TI  - [The differentiation between identity crisis and identity diffusion and its
      impact on treatment].
AB  - The differentiation between an identity crisis, a transient phenomenon that
      usually results (after resolution) in a well-integrated identity with flexible
      and adaptive functioning, and an identity diffusion that is viewed as a basis for
      subsequent personality pathology, has a major impact on the selection of a
      treatment method. A new treatment method (Adolescent Identity Treatment, AIT), a
      modification of Transference Focused Psychotherapy, was developed to treat
      adolescents with identity diffusion in order to improve their relationships with
      friends, parents, and teachers and to help them acquire positive self-esteem,
      clarify life goals and establish a stable identity. In a case study we describe
      the basic approaches of AIT in assessment and treatment.

PMID- 20795521
TI  - [Psychoanalytic-interactional psychotherapy of severely disturbed adolescents].
AB  - Due to specific developmental conditions of adolescence like deficient self
      reflective capacities or reduced potential to articulate, the psychotherapy of
      adolescents is faced with special problems. In adolescents with severe Ego
      structural disorders like Borderline (Development) Disorders these problems are
      increased exponentially. Patients replicate their negative and often traumatic
      relational experiences in everyday life as well as in therapy. The therapeutic
      treatment of relational entanglements often results in malignant repetitions.
      Here the Psychoanalytic-interactional Method (PiM) is suitable as intervention
      where the therapist approaches the patient as a person who influences the
      development positively and strives for Ego-structural advancement within the
      therapeutic relation. The Psychoanalytic-interactional Method allows for the
      adolescence-specific conditions of limited mentalization and particulary for the
      problem of Ego-structural disorders in adolescence. The method is demonstrated by
      treatment sequences of the therapy of a juvenile female patient with Borderline
      (Development) Disorder.

PMID- 20795522
TI  - [Cognitive behavioral therapy for adolescents suffering from complex trauma
      disorder].
AB  - Complex Posttraumatic Stress Disorder and Developmental Trauma Disorder are
      discussed as new diagnostic entities representing the broad spectrum of trauma
      related symptoms of children and adolescents. However, the psychotherapy of
      severe and complex trauma during adolescence is challenging because trauma
      associated symptoms like attachment problems, the expectation of self-inefficacy
      and dissociation may complicate therapeutic work and limit treatment outcome.
      Therefore it is necessary to develop evidence-based treatment approaches for
      these mental disorders. Trauma-focused cognitive-behavioral therapy has been
      successfully evaluated for the treatment of posttraumatic stress disorder. Actual
      treatment approaches combine strategies from Dialectal Behavioral Therapy (DBT)
      with cognitive behavioral techniques of trauma therapy for the treatment of
      complex trauma disorder. This article gives a practical overview about cognitive
      behavioral treatment approaches and discusses problems of their implementation in
      the clinical routine of child and adolescent psychiatrists/psychotherapists.

PMID- 20795523
TI  - [Comorbid antisocial and borderline personality disorders: mentalization-based
      treatment].
AB  - Mentalization is the process by which we implicitly and explicitly interpret the
      actions of ourselves and others as meaningful based on intentional mental states
      (e.g., desires, needs, feelings, beliefs, and reasons). This process is disrupted
      in individuals with comorbid antisocial (ASPD) and borderline personality
      disorder (BPD), who tend to misinterpret others' motives. Antisocial
      characteristics stabilize mentalizing by rigidifying relationships within
      prementalistic ways of functioning. However, loss of flexibility makes the person
      vulnerable to sudden collapse when the schematic representation is challenged.
      This exposes feelings of humiliation, which can only be avoided by violence and
      control of the other person. The common path to violence is via a momentary
      inhibition of the capacity for mentalization. In this article, the authors
      outline their current understanding of mentalizing and its relation to antisocial
      characteristics and violence. This is illustrated by a clinical account of
      mentalization-based treatment adapted for antisocial personality disorder.
      Treatment combines group and individual therapy. The focus is on helping patients
      maintain mentalizing about their own mental states when their personal integrity
      is challenged. A patient with ASPD does not have mental pain associated with
      another's state of mind; thus, to generate conflict in ASPD by thinking about the
      victim will typically be ineffective in inducing behavior change.

PMID- 20795524
TI  - Meaningful use--final at last. Final rule adds flexibility to objectives, eases
      measures.
AB  - The final rule on the EHR incentive plan offers more "flexibility and choice"
      than the daunting proposed rule, adjusting the objectives and scaling back some
      of the measures. Now interested providers just need to figure out how to get with
      the program.

PMID- 20795526
TI  - United RECs of America.

PMID- 20795525
TI  - No harm done? Assessing risk of harm under the federal breach notification rule.
AB  - Provisions within the HITECH Act require that covered entities notify individuals
      if their protected health information is breached. However, the current
      regulation allows an exemption if the risk of harm is slight. Assessing risk can
      be subjective, and privacy officers have been working to create methods to
      conduct and document their analyses.

PMID- 20795527
TI  - Certified meaningful.
AB  - This month providers will begin seeing the first EHR products approved for use in
      the "meaningful use" incentive program. Another piece of the ARRA puzzle is
      falling into place.

PMID- 20795529
TI  - An ARRA timeline.

PMID- 20795528
TI  - Running the numbers on an EHR. Applying cost-benefit analysis in EHR adoption.
AB  - Even with federal incentive payments, providers will be hesitant to adopt EHRs
      without understanding the return on investment. A cost-benefit analysis helps
      determine EHR profitability over time.

PMID- 20795530
TI  - Pacing the ARRA changes. Tackling the ARRA rules and regulations as they come.
AB  - Through the winter and spring healthcare waited for the next round of ARRA
      related regulations. Now they are here, and organizations are tagged with
      implementing compliant programs. How do you get started when it seems that
      everything needs doing at once?

PMID- 20795531
TI  - A first peek at the privacy regulations.

PMID- 20795532
TI  - Aligning HIE. A model to organize networks on core principles, collaborative
      activities.
AB  - An HIE model developed in Florida leverages local and regional networks and
      offers a flexible, scalable framework that aligns them with national health IT
      and exchange priorities.

PMID- 20795533
TI  - E-HIM practice transformation (updated).

PMID- 20795534
TI  - $58 billion to go.

PMID- 20795535
TI  - Memory T Cells. Preface.

PMID- 20795536
TI  - Memory Th1/Th2 cell generation controlled by Schnurri-2.
AB  - Schnurri (Shn) is a large zinc-finger containingprotein, which plays a critical
      role in cell growth, signal transduction and lymphocyte development. There are
      three orthologues (Shn-1, Shn-2 and Shn-3) in vertebrates. In Shn-2-deficient
      mice, the activation of NF-kappaB in CD4 T cells is upregulated and their ability
      to differentiate into Th2 cells is enhanced in part through the increased
      expression of GATA3. Shn-2 is found to compete with p50 NF-kappaB for binding to
      a consensus NF-kappaB motif and inhibit the NF-kappaB-driven promoter activity.
      In addition, Th2-driven allergic airway inflammation was enhanced in Shn-2
      deficient mice. Therefore, Shn-2 appears to negatively control the
      differentiation of Th2 cells and Th2 responses through the repression of NF
      kappaB function. Memory Th1/Th2 cells are not properly generated from Shn-2
      deficient effector Th1/Th2 cells. The expression levels of CD69 and the number
      ofapoptotic cells are selectively increased in Shn-2-deficient Thl/Th2 cells when
      they are transferred into syngeneic host animals, in which memoryh Th1/Th2 cells
      are generated within a month. In addition, an increased susceptibility to
      apoptotic cell death is also observed in vitro accompanied with the increased
      expression of FasL, one of the NF-kappaB-dependent genes. Th2 effector cells
      overexpressing the p65 subunit of NF-kappaB demonstrate a decreased cell survival
      particularly in the lymph node. These results indicate that Shn-2-mediated
      repression of NF-kappaB is required for cell survival and the successful
      generation of memory Th1/Th2 cells. This may point to the possibility that after
      antigen clearance the recovery of the quiescent state in effector Th cells is
      required for the generation of memory Th cells. A repressor molecule Shn-2 plays
      an important role in this process.

PMID- 20795537
TI  - Transcriptional regulation during CD8 T-cell immune responses.
AB  - Naive CD8 T cells differentiate in response to antigen stimulation. They acquire
      the capacity to express multiple effector molecules and mediate effector
      functions that contribute to infection control. Once antigen loads are reduced
      they revert progressively to a less activated status and eventually reach a
      steady-state referred to as "memory" that is very different from that of naive
      cells. Indeed, these "memory" cells are "ready-to-go" populations that acquired
      the capacity to respond more efficiently to antigen stimulation. They modify
      their cell cycle machinery in order to divide faster; they likely improve DNA
      repair and other cell survival mechanisms in order to survive during division and
      thus to generate much larger clones of effector cells; finally, they also mediate
      effector functions much faster. These modifications are the consequence of
      changes in the expression of multiple genes, i.e., on the utilization of a new
      transcription program.

PMID- 20795539
TI  - The role of inflammation in the generation and maintenance of memory T cells.
AB  - Following infection or vaccination, antigen-specific T cells undergo enormous
      expansion in numbers and differentiate into effector cells that control infection
      and modulate other aspects of innate and adaptive immunity. The effector T-cell
      expansion phase is followed by an abrupt period of contraction, during which 90
      95% of antigen-specific T cells are eliminated. The surviving pool of T cells
      subsequently differentiates into long-lived memory populations that can persist
      for the life of the host and mediate enhanced protective immunity following
      pathogen re-infection. The generation and maintenance of memory T-cell
      populations are influenced by a multitude of factors, including inflammatory
      cytokines that can act on T cells at various points during their differentiation.
      Herein, we discuss our current understanding of how inflammation shapes not only
      the quantity and quality of memory T cells, but also the rate at which functional
      memory T-cell populations develop.

PMID- 20795538
TI  - The role of interleukin-2 in memory CD8 cell differentiation.
AB  - The current literature on the role of interleukin (IL)-2 in memory CD8+ T-cell
      differentiation indicates a significant contribution of IL-2 during primary and
      also secondary expansion of CD8+ T cells. IL-2 seems to be responsible for
      optimal expansion and generation of effector functions following primary
      antigenic challenge. As the magnitude of T-cell expansion determines the numbers
      of memory CD8+ T cells surviving after pathogen elimination, these event
      influence memory cell generation. Moreover, during the contraction phase of an
      immune respons where most antigen-specific CD8+ T cells disappear by apoptosis,
      IL-2 signals are able to rescu CD8+ T cells from cell death and provide a durable
      increase in memory CD8+ T-cell counts. At the memory stage, CD8+ T-cell
      frequencies can be boosted by administration of exogenous IL-2 Significantly,
      only CD8+ T cells that have received IL-2 signals during initial priming are able
      t mediate efficient secondary expansion following renewed antigenic challenge.
      Thus, IL-2 signals during different phases of an immune response are key in
      optimizing CD8+ T-cell functions, thereby affecting both primary and secondary
      responses of these T cells.

PMID- 20795540
TI  - The role of OX40 (CD134) in T-cell memory generation.
AB  - Memory T-cell generation is limited by activation-induced cell death during the
      effector T-cell stage. Cell surface proteins are known to transmit signals that
      either accentuate or limit T-cell death after activation. This chapter will focus
      on the TNF-receptor family member OX40, which is expressed on effector T cells
      and when engaged greatly enhances survival of T cells leading to increased memory
      T-cell generation. Targeting OX40 in vivo can alter the fate ofT-cell survival.
      Enhancing OX40 signaling during Ag priming through agonists increases memory T
      cell development, while blocking OX40 signaling decreases the memory T-cell pool.
      These two opposing outcomes provide therapeutic tools for blocking inflammation
      in autoimmune conditions and enhancing immunity in hosts harboring cancer or
      chronic pathogens. OX40 agonists and antagonists are in the first stages of human
      clinical trials and their therapeutic potential will soon be realized.

PMID- 20795541
TI  - The role of precursor frequency in the differentiation of memory T cells: memory
      by numbers.
AB  - Immunological memory is considered the hallmark of adaptive, or acquired,
      immunity. That ability of our immune system to recognize and respond to those
      pathogens we have encountered before not only typifies acquired immunity but has
      provided the basis for the most notable of medical interventions: vaccination.
      Yet, as much as we now know about this process, we are still on the cusp of fully
      understanding how memory T cells develop, how they are maintained and the
      importance of memory T-cell heterogeneity. In this review we will primarily focus
      on our understanding of CD8 T-cell memory generated during acute infections and
      how precursor frequency influences their development and functional attributes.

PMID- 20795542
TI  - CD8 T-cell memory differentiation during acute and chronic viral infections.
AB  - CD8 T cell responses play an important role in protection against intracellular
      parhogens. Memory CD8 T cells mediate rapid clearance of pathogens upon secondary
      infection owing to their elevated frequency, ready localization to peripheral
      sites of infection and their ability to rapidly expand and mount effector
      functions. Such potent long-lasting protective memory CD8 T cells develop in
      acute infections where antigen is effectively cleared. In contrast, chronic
      infections with persistently high viral loads are characterized by CD8 T-cell
      dysfunction. In this chapter we present our current understanding of signals and
      mechanisms that regulate the development of functional long-lived memory CD8 T
      cells during acute infections. This is discussed in the context of proposed
      models of memory differentiation and compared with CD8 T-cell exhaustion and
      altered T-cell homeostasis, as occurs during persistent viral infections.

PMID- 20795543
TI  - Longevity of T-cell memory following acute viral infection.
AB  - Investigation of T-cell-mediated immunity following acute viral infection
      represents an area of research with broad implications for both fundamental
      immunology research as well as vaccine development. Here, we review techniques
      that are used to assess T-cell memory including limiting dilution analysis,
      enzyme-linked immunospot (ELISPOT) assays, intracellular cytokine staining (ICCS)
      and peptide-MHC Class I tetramer staining. The durability of T-cell memory is
      explored in the context of several acute viral infections including vaccinia
      virus (VV), measles virus (MV) and yellow fever virus (YFV). Following acute
      infection, different virus-specific T-cell subpopulations exhibit distinct
      cytokine profiles and these profiles change over the course of infection.
      Differential regulation of the cytotoxic proteins, granzyme A, granzyme B and
      perforin are also observed in virus-specific T cells following infection. As a
      result of this work, we have gained a broader understanding of the kinetics and
      magnitude of antiviral T-cell immunity as well as new insight into the patterns
      of immunodominance and differential regulation of cytokines and cytotoxicity
      associated molecules. This information may eventually lead to the generation of
      more effective vaccines that elicit T-cell memory with the optimal combination of
      functional characteristics required for providing protective immunity against
      infectious disease.

PMID- 20795544
TI  - Principles of memory CD8 T-cells generation in relation to protective immunity.
AB  - Memory T-cell responses are of vital importance in understanding the host's
      response against pathogens and cancer cells and to begin establishing the
      correlation of protection against disease. In this review, we discuss our own
      data in the general context of current knowledge to sketch tentative working
      principles for the induction of protective T-cell responses by vaccination. We
      draw attention to quantitative and qualitative aspects of the initial contact
      with antigen, as well as to the kinetics of events leading to the generation of
      memory T cells thereafter. Our arguments are based on the current distinction of
      memory T cells into two lineages: effector memory T cells (T(EM)) and central
      memory T cells (T(CM)). Our provisional conclusion is that protective T-cell
      responses correlate positively with the T cells of the central memory phenotype.
      In proposing a set of working principles to enable protective memory T cells by
      vaccination we address vaccination both in the context of the immunologically
      inexperienced and immunologically-experienced individual, respectively. Finally,
      we draw attention to the interplay between systemic and local immunity as
      important factors in determining the success of memory T-cell responses in
      protecting the individual. We believe that considerations on the immunodynamics
      of memory induction and maintenance, memory lineage differentiation and their
      relation to protection may help design strategies to control disease caused by
      pathogens and cancer.

PMID- 20795545
TI  - Memory T cells in Rhesus macaques.
AB  - The Rhesus macaque (Macaca mulatta) is one of the best studied species of Old
      World monkeys. DNA sequencing of the entire Rhesus macaque genome, completed in
      2007, has demonstrated that humans and macaques share about 93% of their
      nucleotide sequence. Rhesus macaques have been widely used for medical research
      including drug testing, neurology, behavioral and cognitive science,
      reproduction, xenotransplantation and genetics. Because of the Rhesus macaque's
      sensitivity to bacteria, parasites and viruses that cause similar disease in
      humans, these animals represent an excellent model to study infectious diseases.
      The recent pandemic of HIV and the discovery of SIV, a lentivirus genetically
      related to HIV Type 1 that causes AIDS in Rhesus macaques, have prompted the
      development of reagents that can be used to study innate and adaptive immune
      responses in macaques at the single cell level. This review will focus on the
      distribution of memory cells in the different immunologic compartments of Rhesus
      macaques. In addition, the strategies available to manipulate memory cells in
      Rhesus macaques to understand their trafficking and function will be discussed.
      Emphasis is placed on studies of memory cells in macaques infected with SIV
      because many studies are available. Lastly, we highlight the usefulness of the
      Rhesus macaque model in studies related to the aging of the immune system.

PMID- 20795546
TI  - Memory T-cell subsets in parasitic infections.
AB  - Parasitic infections remain a major health problem throughout the world and
      unlike many viral or bacterial diseases, there are no vaccines to help control
      parasitic diseases. While several important advances have been made that will
      contribute to the development of parasite vaccines, such as cloning of dominant
      parasite antigens and a better understanding of the effector T-cell subsets
      needed for immunity, fundamental questions remain about how to induce long-term
      immunologic memory in vaccines. Here we examine a few of the experimental models
      that have been used to elucidate the nature of the memory T cells that are
      generated during parasitic infections. Although significant hurdles remain in the
      development of parasite vaccines, studies with both protozoa and gastrointestinal
      nematodes suggest that long-term immunity induced by vaccination is a realistic
      goal for control of parasitic infections.

PMID- 20795547
TI  - Antigen specific memory T cells and their putative need for the generation of
      sustained anti-tumor responses.
AB  - Memory T-cell responses to cancer antigens may be an effective way to sustain
      long-term tumor-free survival. However, finding an effective vaccination strategy
      to induce memory T-cell responses toward tumor associated antigens in patients
      with existing disease has proven to be extremely difficult. Immune stimulation
      regimens have been combined with tumor vaccination in an attempt to boost the
      immune response resulting in better vaccine efficacy. In these instances immune
      stimulation alone has shown some promise as a primary tumor therapy, but has been
      less effective at eliciting long-term tumor immunity. Likewise, combining
      systemic adjuvant therapy with tumor antigen vaccination also demonstrated a lack
      of sustained anti-tumor immunity in cancer patients. In this review, we discuss
      whether the immune response generated during immune stimulation is appropriate
      for supporting memory T-cell generation or whether initial tumor regression and
      generation of sustained anti-tumor immunity have different immunological
      signaling requirements.

PMID- 20795548
TI  - Memory T-cell responses and survival in human cancer: remember to stay alive.
AB  - Cancer is a major public health problem worldwide. Accumulating evidence suggests
      that Gtumor-host interactions may in part impact on tumor progression. However,
      the role of inflammation and adaptive immune reaction in cancer emergence, local
      and metastatic invasion and recurrence are still not dearly defined. Pro
      inflammatory mediators are suspected to favor tumor growth and angiogenesis and
      naturally generated T cells with antigenic specificity to tumor associated
      antigens were usually in a state of anergy. Nevertheless, experiments in mouse
      and human showed a significant association between high density of tumor
      infiltrating T cells and improved cancer prognosis. Recently, the global analysis
      of colorectal cancer microenvironment demonstrated that a strong and coordinated
      Th1 adaptive immune response within primary tumors dramatically reduced the risks
      of relapse events. Interestingly the absence of early signs of metastatic
      invasion (lymphovascular emboli) correlated with a significant increase of the
      density of memory T cells in situ. This chapter presents the arguments supporting
      the existence of immunosurveillance mechanisms in human cancer. We will discuss
      the potent role of memory T cells in cancer immunity as well as the opportunities
      of therapeutic strategies uncovered by this new area of investigation.

PMID- 20795550
TI  - Memory T-cell homeostasis and senescence during aging.
AB  - Evidence is accumulating that old individuals are more susceptible to infection
      with organisms to which they were previously immune, indicating that there might
      be a limit to the persistence of immune memory. The prevailing concept is that
      defects in memory T-cell populations result from inexorable end-stage
      differentiation as a result of repeated lifelong antigenic challenge. We discuss
      here mechanisms that might constrain the persistence of memory T cells and
      consider whether humans will suffer from memory T-cell exhaustion as life
      expectancy increases.

PMID- 20795549
TI  - Analysis of vaccine-induced T cells in humans with cancer.
AB  - Over the past several years, progress in the field of tumor immunology has lead
      to advances in active immunotherapy and vaccination as a means ofeliciting tumor
      specific immune responses to mediate tumor regression and clearance. Developing
      vaccines targeted against cancer became an important focus as a therapy following
      the success of viral vaccines in preventing infection and disease. In humans with
      cancer, similar to viral infections, the host immune system is capable of
      recognizing antigens expressed on tumor cells. This similarity allows the
      immunological framework of the viral vaccine to be adapted to the cancer setting
      in hopes of enhancing human T-cell reactivity against tumor. It is generally
      believed that a requirement for tumor destruction to occur is the induction of
      sufficient levels of immune cells with high avidity for recognition of tumor
      antigens. Moreover, the cells must be targeted to the tumor site and be capable
      of infiltrating tumor stroma.2 Several tumor-associated antigens (TAA) have been
      identified in the melanoma model which has allowed for immunization trials to
      evaluate therapeutic potential of tumor-specific T-cell induction. Some clinical
      trials reported limited success ofT-cell mediated tumor rejection,
      reportingpartial or complete regression in 10 to 30% of patients. Although tumor
      regression was not observed following active immunization in vivo, ex vivo assays
      evaluating TAA-specific T cells demonstrated tumor recognition and subsequent T
      cell activation suggesting that tumor-specific T-cell induction indeed occurs but
      alone is not adequate to induce tumor regression. Recently, the usefulness and
      success of active-specific immunization (ASI) against TAAs as a means ofeliciting
      a tumor-specific immune response leading to tumor regression and clearance has
      been a topic of debate and discussion.

PMID- 20795551
TI  - Variability among hospitals and staff in collection of race, ethnicity,
      birthplace, and socioeconomic information in the greater San Francisco Bay Area.
AB  - Hospital data on race, ethnicity, birthplace, and socioeconomic status (SES) are
      important for identifying health disparities; however, little is known about the
      consistency across and within hospitals in the collection of these data. This
      study examined hospital practices and policies for the collection of these data
      and the variability across hospital staff and hospital characteristics. Surveys
      were mailed to selected hospital staff in all 59 hospitals in the San Francisco
      Bay Area, and completed questionnaires were received from 141 (of 367) staff from
      41 hospitals. While most hospitals collect race/ethnicity (83% always collect)
      and birthplace (60% always or sometimes collect), few hospitals collect patient
      information on education (75% never collect) and income (55% never collect).
      There is vast variability in reported practices and policies across staff within
      hospitals, and variability across hospitals with regards to certain hospital
      characteristics. Nationally standardized policies, including standards for where,
      what, and when these data should be collected, are necessary for accurate and
      uniform data collection, and for effectively addressing health disparities.

PMID- 20795553
TI  - Electronic capture and communication of synoptic cancer data elements from
      pathology reports: results of the Reporting Pathology Protocols 2 (RPP2) project.
AB  - Pathology reports represent a rich data source for cancer registries. The College
      of American Pathologists (CAP) Cancer Checklists present pathology reports in
      synoptic form and allow registries to be updated electronically. To assess the
      challenge of employing the CAP Cancer Checklists in pathology laboratories and
      transmitting that information to cancer registries, we conducted a pilot project:
      the Reporting Pathology Protocols project (RPP2). The RPP2 project was a multi
      year, "proof of concept" demonstration that assessed pathology report-generated
      data for 3 CAP Cancer Checklists (breast, prostate, and melanoma) in several
      different cancer registry-pathology laboratory combinations in 3 states.
      Collaborating pathology laboratories and state cancer registries in California,
      Maine, and Pennsylvania identified key questions (queries) to address in the
      course of the project, developed and tested standardized HL7 messaging
      specifications to link senders and recipients, and then assessed the actual
      process results using either parallel reporting or retrospective-prospective
      cases for each tumor type. Successful electronic transfer and capture of
      pertinent data elements for numerous examples of each tumor type was accomplished
      in each participating cancer registry/reporting laboratory/information system
      combination. We noted shortcomings in the electronically encoded CAP Checklists
      as opposed to text-based reports, particularly for breast cancers. We uncovered
      opportunities to improve Checklists and the information systems that incorporate
      them. Workflow, productivity, and timeliness of reporting are areas where
      electronically encoded reports may enhance cancer registry processes. The
      accuracy and completeness of electronically encoded data appears largely
      comparable to text-based data, but subject to the degree of synchrony between the
      formats of text-based and electronic reports.

PMID- 20795552
TI  - Comorbid mental disorders in hospital records of Hispanic patients diagnosed with
      cancer in Connecticut.
AB  - Comorbid mental disorder is a potential prognostic factor among newly diagnosed
      cancer patients, including the growing numbers of Hispanic Americans. This study
      examined the frequency of recording of comorbid mental conditions in hospital
      records for 737 newly diagnosed Hispanic American cancer patients (358 men and
      379 women), ascertained from the population-based Connecticut cancer registry. A
      comorbid mental disorder(s) was found for 112 patients (15.2%), including 20.3%
      of women and 9.8% of men. Of these 112 patients, 80% had a specific psychotropic
      medication(s) recorded, thus supporting the presence of comorbidity. Prevalence
      of a comorbid mental disorder declined with age but did not differ by primary
      language (Spanish/bilingual vs. English). Similar studies are needed of Hispanic
      (and non-Hispanic) patients in other central cancer registries, for potential
      large-scale, population-based studies of comorbid mental disorder in relation to
      prognosis.

PMID- 20795554
TI  - Comparative evaluation of uterine cancer staging data using two different staging
      systems, 2001-2005.
AB  - OBJECTIVE: This study compares directly coded Summary Stage 2000 (SS2000) with
      that of Collaborative Stage (CS) Derived Summary Stage 2000 (DeSS2000) for cases
      of uterine cancer diagnosed in the years 2001-2005 using population-based cancer
      registry data. METHODS: Data included in this study were from central cancer
      registries that participated in the Surveillance, Epidemiology, and End Results
      (SEER) Program or the National Program of Cancer Registries (NPCR) and met data
      quality criteria for 2001-2005 covering approximately 80% of the US population.
      The data for diagnosis years 2001-2003 (pre-CS) were compared with those for
      diagnosis years 2004-2005 (post-CS) to review any shifts in staging between the
      pre- and post-CS years. RESULTS: Slight decreases were observed in the percent of
      cases staged as in situ and localized uterine cancer with a corresponding slight
      increase in percent of regional and distant uterine cancer cases. In contrast to
      the findings in 2001-2003, no regional, (not otherwise specified) uterine cancer
      cases were reported in 2004-2005. Lastly, in the unstaged/unknown group of
      uterine cases, there was a slight decrease in the percent of cases. DISCUSSION:
      The lack of no regional, NOS, and the decrease in unstaged cases indicate
      improvement in staging of uterine cancer diagnosed in 2004-2005. These findings
      suggest that the CS DeSS2000 data are of high quality for uterine cancer and can
      be used to study the stage distribution of the cancer.

PMID- 20795555
TI  - Strategic planning for the TotalCare Cancer Center at Los Alamitos Medical Center
      with data analysis of caseloads before and after opening.
AB  - PURPOSE: To evaluate the significance of the new TotalCare Cancer Center at Los
      Alamitos Medical Center during its first 6 months of operation. This study
      evaluates the short-term impact that the center has had on patient caseload in
      the areas of infusion and radiation oncology. METHODS: Two 6-month time blocks
      were evaluated using the cancer registry database. Cases were reviewed to
      determine the number of patients that received chemotherapy and radiation therapy
      at Los Alamitos Medical Center prior to and directly after the initiation of the
      TotalCare Cancer Center to determine if the initial goals laid out by the
      administration were met. RESULTS: The same number of patients received
      chemotherapy at the hospital prior to and directly after the center was opened
      and few patients received radiation therapy in the first 6 months after the
      center was opened. CONCLUSION: The TotalCare Cancer Center did not appear to have
      the desired impact on caseload as was desired by the administration within the
      first 6 months of operation. However, overall caseload did increase over that
      time period, concluding that there may be a lag in overall affect of the new
      center.

PMID- 20795557
TI  - Evaluating quality of census tract data in the NPCR dataset.
AB  - BACKGROUND: Knowledge of data quality is essential for accurate interpretation
      and use of cancer data by cancer control and prevention programs and researchers.
      OBJECTIVE: To assess the quality of census tract information in the Centers for
      Disease Control and Prevention's (CDC) National Program of Cancer Registries
      (NPCR) dataset. This assessment will guide analyses using census tract
      information from the NPCR dataset. METHODS: The 2001-2005 data submitted for the
      2008 NPCR Cancer Surveillance System (NPCR-CSS) were used to calculate the
      overall and registry-specific proportion of records that included information on
      the variable census tract 2000 (NAACCR item #130). RESULTS: For diagnosis years
      2001-2005 combined, valid information on census tract was submitted for 59% of
      the records in the NPCR dataset. Of the 41 NPCR-supported registries evaluated,
      22 (54%) submitted valid census tract data on > = 90% of total incidence records,
      and 10 (24%) submitted valid census tract data on < = 5% of the records. Across
      individual diagnosis years, 53%, 59%, 60%, 60% and 61% of records included valid
      information for 2001, 2002, 2003, 2004, and 2005, respectively.
      CONCLUSION/IMPLICATIONS: The completeness of census tract data varied by registry
      and diagnosis year. The differences in completeness of census tract data can
      reflect changes in the number of registries that submit such data and changes in
      the number of registries that meet data quality standards. In addition, there may
      be resource issues or other un-identified barriers for not being able to submit
      these data. Complete data on census tract from all registries is desirable for
      national level research related to spatial analyses, although information from
      registries with complete census tract data may be usable for local, state, or
      regional studies or national estimates.

PMID- 20795556
TI  - The rubber meets the road: results of the CSv2 field study on the collection of
      site-specific factors.

PMID- 20795558
TI  - Change management: a must-have for 2010 implementation.

PMID- 20795559
TI  - Picture perfect staffing in today's economy.
AB  - This article describes the methods one Cancer Registry Department used to justify
      adequate staffing and obtain approval for an increase in full-time employees
      (FTEs). Each day it is getting more difficult to keep up with registry work while
      hospitals are compensating for loss of income by implementing changes that often
      impact staffing. Departments such as Cancer Registries, which are historically
      understaffed, must find ways to keep up with increasing workloads. If a hospital
      intends to maintain accreditation by the American College of Surgeons (ACoS)
      Commission on Cancer (CoC) and the treatment facility of choice for cancer
      patients, it is the opinion of this author that administrators must realize that
      adequate staff for the Cancer Registry Department is essential.

PMID- 20795560
TI  - Write on!

PMID- 20795561
TI  - When you feel uninspired.

PMID- 20795562
TI  - When did that rule change?--revisited.

PMID- 20795563
TI  - Evaluation of passive surveillance for NTD-affected births in Alaska: a case
      verification study, birth years 1996-2007.
AB  - INTRODUCTION: Neural tube defects (NTDs), including spina bifida, encephalocele,
      and anencephaly, are severe congenital conditions that are readily identifiable
      at birth and therefore less likely than other birth defects to be misdiagnosed or
      under-reported. We tested the hypothesis that, because of the relatively
      straightforward diagnosis of NTDs, accurate estimates of NTD prevalence can be
      directly estimated from reports to the Alaska Birth Defects Registry (ABDR)--a
      passive surveillance system receiving reports from all Alaska hospitals and other
      sources. METHODS: We reviewed medical records for potential NTD-affected births
      identified by the ABDR and Alaska birth certificates. Case verification findings
      were linked to Alaska birth certificate data and overall and specific positive
      predictive values (PPV) computed. RESULTS: Alaska Birth Defects Registry-specific
      PPV was 44%. Positive predictive values did not differ by Alaska Native status
      even when data were stratified by number of NTD reports submitted, age at
      diagnosis, or birth year. Systematic exclusion of reporting sources with poor PPV
      resulted in a 28% improvement of PPV to 57%. The Alaska Native/non-Native ratio
      for unconfirmed NTD reports (0.7) was identical to the Alaska Native/non-Native
      ratio for confirmed NTD cases. CONCLUSIONS: Unverified ABDR registry data is
      useful for identifying relative differences in NTD risk for Alaskan populations,
      but is unreliable for calculating NTD prevalence estimates or for evaluating
      preventive interventions. Systematic approaches to improving PPV may be useful
      for generating NTD prevalence estimates from unverified registry data when case
      verification is impractical.

PMID- 20795564
TI  - Developing a database management system to support birth defects surveillance in
      Florida.
AB  - The value of any public health surveillance program is derived from the ways in
      which data are managed and used to improve the public's health. Although birth
      defects surveillance programs vary in their case volume, budgets, staff, and
      objectives, the capacity to operate efficiently and maximize resources remains
      critical to long-term survival. The development of a fully-integrated relational
      database management system (DBMS) can enrich a surveillance program's data and
      improve efficiency. To build upon the Florida Birth Defects Registry--a statewide
      registry relying solely on linkage of administrative datasets and unconfirmed
      diagnosis codes-the Florida Department of Health provided funding to the
      University of South Florida to develop and pilot an enhanced surveillance system
      in targeted areas with a more comprehensive approach to case identification and
      diagnosis confirmation. To manage operational and administrative complexities, a
      DBMS was developed, capable of managing transmission of project data from
      multiple sources, tracking abstractor time during record reviews, offering tools
      for defect coding and case classification, and providing reports to DBMS users.
      Since its inception, the DBMS has been used as part of our surveillance projects
      to guide the receipt of over 200 case lists and review of 12,924 fetuses and
      infants (with associated maternal records) suspected of having selected birth
      defects in over 90 birthing and transfer facilities in Florida. The DBMS has
      provided both anticipated and unexpected benefits. Automation of the processes
      for managing incoming case lists has reduced clerical workload considerably,
      while improving accuracy of working lists for field abstraction. Data quality has
      improved through more effective use of internal edits and comparisons with values
      for other data elements, while simultaneously increasing abstractor efficiency in
      completion of case abstraction. We anticipate continual enhancement to the DBMS
      in the future. While we have focused on enhancing the capacity of our DBMS for
      birth defects surveillance, many of the tools and approaches we have developed
      translate directly to other public health and clinical registries.

PMID- 20795565
TI  - Development of web-based geocoding applications for the population-based Birth
      Defects Surveillance System in New York state.
AB  - Geographic information systems (GIS) have been widely used in mapping health data
      and analyzing the geographic distribution of disease. Mapping and spatially
      analyzing data normally begins with geocoding, a process of assigning geographic
      coordinates to an address so that it can be displayed and analyzed on a map. The
      objectives of this project were to develop Web-based geocoding applications for
      the New York State birth defects surveillance system to geocode, both
      automatically and interactively, the birth defect cases of the Congenital
      Malformations Registry (CMR) and evaluate the geocoding results. Geocoding
      software, in conjunction with a Java-based development tool (J Server), was used
      to develop the Web-based applications on the New York State Department of
      Health's Health Commerce System. The Web-based geocoding applications have been
      developed and implemented for the New York State birth defects surveillance
      system. These menu-driven applications empower users to conduct geocoding
      activities using only a PC and a Web browser without the installation of any GIS
      software. These powerful tools provide automatic, real-time, street-level
      geocoding of the routinely collected birth defects records in the CMR. Up to 92%
      of the CMR records have been geocoded with addresses exactly matched to the
      reference addresses on house number, street name, and city or zip code.

PMID- 20795566
TI  - Geocoding capacity of birth defects surveillance programs: results from the
      National Birth Defects Prevention Network Geocoding Survey.
AB  - A Web-based survey focusing on geocoding of birth defects data was developed and
      administrated to gain an understanding of the capacity of state birth defects
      programs to geocode maternal residence and to identify barriers to geocoding
      birth defects data. The survey consisted of 21 questions related to geocoding of
      maternal residence, type of software used, barriers to geocoding, and data
      linkage. In August 2007, an e-mail with a Web link to the survey was sent to all
      state birth defects program contacts in the United States, including the District
      of Columbia, Puerto Rico, and the Centers for Disease Control and Prevention
      (CDC) requesting they complete the online survey. By October 2007, 39 (74%) out
      of 53 birth defects program contacts completed the survey. Although nearly all
      birth defects programs collect maternal residential data, many are not currently
      geocoding that data. Results indicated that 97% of the programs that completed
      the survey reported they collected data on maternal residence, 53% of which
      reported that the birth defects surveillance data were geocoded to the street
      address level using maternal residential address at delivery. Twenty six percent
      of the programs that do not currently geocode the data identified "Software and
      address reference file are not available" as the most significant barrier to
      geocoding; another 16% chose "Lack of funding" as the most significant barrier to
      geocoding. Since geocoding is an important component of spatial analyses used to
      detect potential clusters of birth defects, leveraging resources to overcome the
      barriers that prevent programs from geocoding is important.

PMID- 20795567
TI  - A new registry of congenital anomalies in Iran.
AB  - BACKGROUND: Registration of the occurrence of birth defects is now being
      performed in about 50 countries in the world as the baseline system for control
      and prevention of congenital anomalies. The principal aim of this program was to
      introduce and establish a monitoring system of congenital anomalies in the
      Northwest of Iran as a basis for planning and assessing prevention and control
      interventions. METHODS/DESIGN: Some of the registry systems of the European
      network countries, the United States of America, and the United Arab Emirates
      were studied in terms of data collection, process, analysis, use, and evaluation
      of the system to find the minimum requirements for setting up a local registry in
      Iran. Key end users of the local Iranian system met and determined the minimum
      requirements for operation of the registry. RESULTS: End users identified the
      minimum data required to establish a local hospital-based registry as:
      child/mother identification number, child/mother hospital record number, type of
      anomaly, gender, date of diagnosis, mother's age at delivery, family history of
      anomaly (optional field), familial marriage (optional field), date of death (if
      any). Initial results show a birth prevalence rate of 1.7% for all reportable
      defects combined. CONCLUSION: This program will provide some essential data as an
      epidemiological tool for local investigations, information for health service
      planners, for clinicians, and for genetic counseling. The program may also help
      to identify regional interventions that could help to prevent and control
      congenital anomalies in the study population. Some of these interventions may be
      specific to the study population while others may have more general applications
      in similar areas and communities.

PMID- 20795568
TI  - Data directions.

PMID- 20795569
TI  - The Inquiry and Response System: Standard 4.6--understanding compliance and
      commendation.

PMID- 20795570
TI  - The 411 on 988.

PMID- 20795571
TI  - Justifying registry operations.

PMID- 20795572
TI  - Resident physician operative times during cataract surgery.
AB  - BACKGROUND AND OBJECTIVE: To determine resident physician operative times
      surrounding their 45th, 86th, and 121st cataract surgery. PATIENTS AND METHODS:
      Retrospective chart review of 375 surgical records of 25 ophthalmology residents.
      Groups were compared with each other and to a published surgeon. RESULTS: The
      mean operative times of surgeries 43 to 47, 84 to 88, and 119 to 123 were 39.9,
      30.0, and 27.2 minutes, respectively. Surgical time decreased 25% from the 45th
      to the 86th case (P = .0002) and 9% from the 86th to the 121st case (P = .2049).
      Compared with a published surgeon's time of 26.8 minutes, residents' times were
      significantly longer around their 45th (P = .0001) and 86th surgery (P = .0012),
      but nearly identical around the 121st surgery (P = .7022). CONCLUSION:
      Significant decreases in operative time occurred between the 45th and 86th case.
      Smaller decreases occurred after the 86th case. Residents' operative times
      approach that of a published ophthalmologist around the 121st case.

PMID- 20795573
TI  - Bleb morphology characteristics and effect on positional intraocular pressure
      variation.
AB  - BACKGROUND AND OBJECTIVE: To study bleb morphology and positional intraocular
      pressure (IOP) change (IOP supine to IOP sitting). PATIENTS AND METHODS: In this
      observational case series, blebs were graded for height, extent, vascularity,
      microcysts, and "ring of steel." Positional IOP change was analyzed using the
      paired t test. Associations between IOP change and bleb morphologies were
      evaluated by regression adjusting for inter-eye dependency. RESULTS: Ninety-five
      eyes of 68 subjects were included. Decreased bleb height (P = .05), absence of
      microcysts (P = .02), and increased bleb vascularity (P = .02) were associated
      with larger positional IOP change. Twenty patients with a filter in one eye and a
      medically treated fellow eye had larger positional IOP change in the medically
      treated eye (6.1 vs 4.6 mm Hg, respectively; P = .01). CONCLUSION: Successful
      filtration surgery results in both lower IOP and less positional IOP change
      compared with medically treated eyes. Bleb features associated with smaller
      positional IOP change include higher elevation, microcysts, and less vascularity.

PMID- 20795574
TI  - Sclerochorioretinal abnormalities in hypercholesterolemic rabbits treated with
      rosiglitazone.
AB  - BACKGROUND AND OBJECTIVE: To evaluate early retinal, choroidal, and scleral
      abnormalities induced by a hypercholesterolemic diet and the prevention of these
      abnormalities after oral administration of rosiglitazone in rabbits. MATERIALS
      AND METHODS: Fifty-four New Zealand rabbits were divided into four study groups:
      control group, normal diet; group 1, hypercholesterolemic diet; group 2,
      hypercholesterolemic diet associated with daily administration of 3 mg of
      rosiglitazone from day 14 after beginning the diet; and group 3,
      hypercholesterolemic diet associated with daily administration of 3 mg of
      rosiglitazone since the beginning of the experiment. Sclera and choroid underwent
      histologic and histomorphometric analyses. Retina underwent immunohistochemical
      analysis with anti-calretinin and anti-glial fibrillary acidic protein (GFAP)
      antibodies. RESULTS: No abnormalities were observed in the control group. Group 1
      had significant increases in scleral and choroidal thicknesses compared with the
      control group (P < .01) and group 3 (P < .05). Group 1 presented significant
      increases in immunoreactivity (P < .001) to the anti-calretinin antibody compared
      with the other groups. Groups 2 and 3 had significant (P < .002) increases in
      calretinin immunoreactivity compared with the control group. GFAP was negative in
      all groups. CONCLUSION: The hypercholesterolemic diet induced early retinal,
      choroidal, and scleral abnormalities. Rosiglitazone preserved the structural
      anatomy.

PMID- 20795576
TI  - Comparison of 20- and 25-gauge vitrectomy for primary repair of rhegmatogenous
      retinal detachment.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the outcome of 25-gauge transconjunctival
      pars plana vitrectomy and compare it with that of 20-gauge pars plana vitrectomy
      for primary repair of rhegmatogenous retinal detachment. PATIENTS AND METHODS: A
      retrospective study of a consecutive series of 166 eyes of 164 patients who
      underwent pars plana vitrectomy for primary rhegmatogenous retinal detachment was
      performed. One hundred nineteen eyes underwent 25-gauge vitrectomy and 47 eyes
      underwent 20-gauge vitrectomy. RESULTS: The anatomic success rates after the
      initial surgery in the 25-gauge vitrectomy and 20-gauge vitrectomy groups were
      93.3% and 91.5%, respectively. The median visual acuity improved significantly
      from 20/80 preoperatively to 20/30 postoperatively in the 25-gauge group, and
      from 20/90 to 20/30 in the 20-gauge group. CONCLUSION: Good anatomic and
      functional results were achieved with 25-gauge vitrectomy and the outcomes
      compared favorably with those of 20-gauge vitrectomy for the treatment of
      rhegmatogenous retinal detachment.

PMID- 20795575
TI  - Clinical course of choroidal neovascularization secondary to angioid streaks
      treated with intravitreal bevacizumab.
AB  - BACKGROUND AND OBJECTIVE: To evaluate visual acuity and anatomical outcomes of
      choroidal neovascularization (CNV) associated with angioid streaks after
      treatment with intravitreal bevacizumab injections. PATIENTS AND METHODS: Best
      corrected visual acuity, optical coherence tomography measurements (OCT),
      fluorescein and indocyanine green angiography, and ophthalmoscope examination at
      baseline and at each follow-up visit were performed. Five patients with CNV
      associated with angioid streaks were treated with injections of intravitreal
      bevacizumab (1.25 mg/0.05 mL). Re-treatment was recommended with symptomatic
      lesions, new subretinal hemorrhages, leakage on fluorescein and indocyanine green
      angiography, and/or fluid documented by OCT. Follow-up ranged between 18 and 32
      months. RESULTS: All eyes showed an improvement of visual acuity and were treated
      with at least four injections of intravitreal bevacizumab. Reduction of the
      leakage shown by fluorescein angiography and OCT was noted in all patients.
      CONCLUSION: Intravitreal bevacizumab appears to be effective in stabilizing and
      recovering visual acuity in eyes with CNV associated with angioid streaks.
      Patients with early symptoms might benefit more.

PMID- 20795577
TI  - Reproducibility of an analysis software for qualitative observation of Elschnig
      pearls.
AB  - BACKGROUND AND OBJECTIVE: To determine the reproducibility of a semi-objective
      analysis software for the morphological analysis of single Elschnig pearls from
      retroillumination images of posterior capsule opacification. PATIENTS AND
      METHODS: In this prospective study, images of eyes with varying degrees of
      regeneratory posterior capsule opacification and the presence of Elschnig pearls
      were taken. The size and morphology of single Elschnig pearls was evaluated from
      consecutive images using an analysis method called PearlTracer using three
      different modes: snake selection, where a few points detected the pearl border
      automatically; diameter circle selection, a circle function; and polygon
      selection, where several points were connected by straight lines. The
      interobserver and intraobserver reproducibility and the limits of the different
      modes concerning contrast were assessed. RESULTS: One hundred fifty-eight
      retroillumination images of 55 eyes of 50 patients were included with a total of
      857 pearls being analyzed. A high interobserver reproducibility was found, as
      well as a high intraobserver reproducibility. Furthermore, a significant
      difference in the pearl size and the pearl morphology between the three analysis
      features of the software was found. CONCLUSION: For the observation of single
      Elschnig pearls and their morphological changes, the semi-objective PearlTracer
      analysis software was found to be a highly reproducible and useful method.

PMID- 20795578
TI  - A modified technique for extracting a dislocated lens with perfluorocarbon
      liquids and viscoelastics.
AB  - The authors describe a modified technique for extraction of a dislocated
      crystalline lens or large and hard lens fragments displaced into the vitreous
      cavity. An ophthalmic viscosurgical device was used around and on top of the
      heavy liquid bubble to keep the lens centered and less mobile for easier
      phacofragmentation or removal by the cutting-suction probe. This technique was
      used in 10 eyes, including cases of traumatic dislocation and Marfan syndrome,
      with excellent anatomical results and no complications that could be attributed
      to the surgical technique. The technique has also been used to retrieve and
      reposition dislocated intraocular lenses.

PMID- 20795579
TI  - Vaccine cold chain: Part 2. Training personnel and program management.
AB  - The Centers for Disease Control and Prevention reports that professionals in
      clinic settings may not be adequately storing and handling vaccine, leading to
      insufficient immunity of vaccinated individuals. Part 2 of this article provides
      information about the importance of adequate personnel training and program
      management policies and procedures needed to implement and maintain an effective
      vaccine cold chain program.

PMID- 20795580
TI  - A health promotion program at a Japanese newspaper undergoing restructuring.
AB  - Occupational health activities based on a health promotion philosophy and focused
      on primary and secondary prevention were introduced at a Japanese newspaper
      company where restructuring had occurred. Japanese metabolic syndrome diagnostic
      standards were used to determine changes in certain lifestyle disease risk
      factors over 10 years. The amount of change from 1998 to 2007 was determined, and
      two groups (i.e., 1998 and 2007) were compared using paired t-tests. Results
      suggested that the occupational health activities focused on primary prevention
      had been effective. The authors concluded that, in situations where industrial
      change and corporate restructuring are occurring, occupational health activities
      based on a health promotion philosophy and focused on primary and secondary
      prevention are more effective than diagnostic activities and other types of
      health management focused on tertiary prevention.

PMID- 20795581
TI  - Older inmates' pursuit of good health: a focus group study.
AB  - Many intersecting factors, including the graying of the broader society, a
      paradigm shift away from rehabilitation, fewer opportunities for parole, and
      retrospective prosecutions, contribute to an exponential increase in number of
      older inmates. Elderly prisoners are likely to live in small, tight quarters with
      other inmates; have chronic health conditions; and encounter multiple barriers to
      health promotion. Using focus groups, data on perceived challenges to health
      promotion and self-care strategies were collected from 42 male inmates 50 and
      older. Cost issues, prison personnel and policies, food concerns, fellow inmates,
      and personal barriers challenged older inmates' abilities to maintain their
      health in prison. However, they did engage in self-care strategies, including
      accessing resources and support, staying positive, managing diet and weight,
      engaging in physical activity, and protecting self. A key motivator for pursuing
      good health was to be respected and perceived as healthy and strong by fellow
      inmates. Development and testing of programs to enhance inmates' self-management
      of chronic conditions and to facilitate health promotion are in order.

PMID- 20795582
TI  - Time travel: the lived experience of providing feeding assistance to a family
      member with dementia.
AB  - A major concern facing family members of people with advanced dementia is
      deciding how to provide food and water. Nurses play a significant role in
      supporting mealtimes, yet little is known about the meaning of mealtime for
      family caregivers of people with dementia. The purpose of this phenomenological
      study was to explore the experience of providing feeding assistance to a family
      member with dementia from the perspective of community and nursing home family
      caregivers. Data were collected through in-depth interviews with 16 family
      caregivers of individuals with advanced dementia. Analysis revealed that the
      experience was likened to living in a time warp whereby family caregivers were
      propelled from pleasant memories of the past, to the stark reality of the
      present, to a foreboding and uncertain future. Findings can guide nurses to
      dialogue with family members and to ensure that the full spectrum of mealtime is
      preserved.

PMID- 20795583
TI  - Lay health mentors in community-based older adult disability prevention programs:
      provider perspectives.
AB  - In this study, we explored provider perspectives on the benefits of and
      implementation challenges in using lay health mentor peers in a community-based
      replication of an efficacious 12-month older adult disability prevention program.
      In addition, we describe the association of the mentor program with site features
      and program completion. We conducted semi-structured telephone interviews with
      nurses, social workers, and site managers and obtained primary data on site
      features and secondary data on program completion. Major themes included the
      importance of the health mentor program and implementation challenges. Sites with
      mentor programs were more likely to have older adults complete the program
      compared with sites without mentor programs. Rural, small, and less diverse sites
      were more likely to have health mentor programs than urban, large, and more
      diverse sites. Implications include a need to fund more lay health mentor
      programs, obtain adequate staffing including minority staff for health mentor
      support, and implement strategies to improve program efficiency.

PMID- 20795584
TI  - Late onset secondary cataract following implantation of an iris-fixated phakic
      intraocular lens.
AB  - PURPOSE: To report a case of bilateral late onset anterior cortical cataract
      following implantation of an iris-fixated phakic intraocular lens (pIOL).
      METHODS: Single observational case report. RESULTS: Three and a half years
      following uncomplicated consecutive implantation of iris-fixated pIOL in both
      eyes, anterior cortical cataract changes inferiorly emanating from the site of
      enclavation of the lens in the right eye were noted. By 7 years after
      implantation, anterior cortical cataract changes were seen emanating from the
      enclavation sites superiorly and inferiorly in both eyes. These cataracts did not
      cause any loss of corrected distance visual acuity. CONCLUSIONS: This case
      demonstrates that a potential complication of an iris-fixated pIOL is late onset
      secondary cataract formation.

PMID- 20795585
TI  - Spontaneous improvement of channel deposits following Intacs implantation.
AB  - PURPOSE: To report a case of filamentous crystalline channel deposits and stromal
      haze extending outside the channel, which continued to worsen more than 3 years
      after implantation before eventually improving without significant intervention.
      METHODS: A 48-year-old woman presented for refractive surgery evaluation.
      Uncorrected visual acuity was 20/400 in both eyes. Ocular history was significant
      for mild blepharitis but was otherwise normal. Approximately 4 months after
      bilateral Intacs (KeraVision) implantation, the patient developed intrachannel
      deposits in both eyes, which had increased significantly at 3-year follow-up.
      RESULTS: The intrachannel deposits and haze spontaneously improved, and 9 years
      following implantation few deposits and little haze remained. CONCLUSIONS:
      Channel deposits, opacification, and haze are widely reported complications
      following the implantation of intrastromal corneal ring segments. Such deposits
      and opacifications are generally not clinically significant and may resolve
      spontaneously.

PMID- 20795586
TI  - Fusarium keratitis 3 weeks after healed corneal cross-linking.
AB  - PURPOSE: To report a case of Fusarium solani keratitis after corneal cross
      linking (CXL) treatment. METHODS: A 23-year-old woman presented with corneal
      ulcer 4 weeks following a CXL procedure. RESULTS: Microbiological studies
      revealed Fusarium species as the etiological pathogen. CONCLUSIONS: Fusarium
      species may cause infectious crystalline keratopathy after corneal CXL treatment.

PMID- 20795587
TI  - Mental health parity legislation.
AB  - Although recognition and treatment of mental health disorders have become
      integrated into routine medical care, inequities remain regarding limits on
      mental health outpatient visits and higher copayments and deductibles required
      for mental health services when accessed. Two federal laws were passed by
      Congress in 2008: The Paul Wellstone and Pete Domenici Mental Health Parity and
      Addiction Equity Act and the Medicare Improvements for Patients and Providers
      Act. Both laws became effective on January 1, 2010. The purpose of this article
      is to discuss provisions of each act and provide clinical examples describing how
      patients are affected by lack of parity and may potentially benefit from
      implementation of these new laws. Using available evidence, we examine the
      potential strengths and limitations of mental health parity legislation from the
      health policy perspectives of health care access, cost, and quality and identify
      the important role of nurses as patient and mental health parity advocates.

PMID- 20795588
TI  - Using hypnosis as adjunct care in mental health nursing.
AB  - Although hypnosis was accepted in 1958 by the American Medical Association as an
      adjunct treatment, it remains an underused modality for alleviation of clients'
      suffering. This hesitancy to apply established practices that show efficacy in
      patient care may be due to a general lack of cognizance about the therapeutic
      benefits of hypnosis or a reluctance to learn skills based on preconceptions
      about hypnosis itself. The purpose of this article is to provide evidence of the
      efficacy of hypnosis as an adjunct treatment in the healing professions and
      explain hypnosis in a manner consistent with the core values of nursing as
      defined by the American Nurses Association. Implications for mental health
      nursing practice will be explored.

PMID- 20795589
TI  - Potential adverse effects of discontinuing psychotropic drugs.
AB  - For nurses in clinical practice, understanding the pharmacology of drugs their
      patients take is relevant to understanding their therapeutic uses, side effect
      profiles, and adverse discontinuation effects. In this article, the last of a
      four-part series, the discontinuation effects of the following psychotropic drugs
      are described: benzodiazepine drugs (which have hypnotic, anti-anxiety, and
      anticonvulsant effects), non-benzodiazepine drugs (used for insomnia), glutamate
      modulating drugs, opioid receptor agonist drugs (used as analgesics for the
      treatment of various pain conditions), and stimulant drugs. Serious adverse
      effects are likely to occur only after abrupt discontinuation of benzodiazepine
      drugs, and they should almost always be tapered. Prominent discontinuation
      effects are seen with opioid and stimulant drugs, but these are usually not
      serious. Tapering medication, rather than abruptly stopping them, can avoid or
      minimize the potential adverse discontinuation effects associated with most
      psychotropic drugs.

PMID- 20795591
TI  - Implications of an aging population for mental health nurses.
AB  - The rapidly increasing numbers of older adults with dementia and other mental
      health problems throughout the world have huge ramifications for nurses who will
      care for these individuals, as well as for health care systems. This article
      explores some current problems in the health care systems and makes suggestions
      for better, more efficient ways to meet the growing mental health needs of the
      aging population. It also addresses moral-ethical dilemmas that will likely
      affect mental health nurses caring for this population.

PMID- 20795590
TI  - Treatment settings and metabolic monitoring for people experiencing first-episode
      psychosis.
AB  - Monitoring for metabolic sequelae of antipsychotic medications is inconsistent in
      clinical settings. In this study, frequency of such monitoring in 40 individuals
      experiencing a first episode of psychosis was analyzed according to the setting
      in which they received treatment (i.e., inpatient unit, outpatient clinic, or
      metabolic screening clinic). The traditional outpatient clinic was the least
      likely of the three settings to monitor blood glucose, blood pressure, weight,
      and waist circumference. In any setting, blood lipids were measured in only 2 of
      the 40 patients. Reasons for these findings and recommendations for reducing
      barriers to screening are presented.

PMID- 20795592
TI  - Psychotropic medications and falls in older adults.
AB  - Falls are a common problem among older adults that may be exacerbated by the
      addition of psychotropic medications. Within each drug class, some medications
      have lower risk of falls. As a result, a comprehensive effort to decrease falls
      begins with a review of medications. Drug-drug interactions and polypharmacy are
      widespread due to the number of medications older adults consume. Nurses can
      eliminate unnecessary medications and seek safer alternatives for potentially
      inappropriate medications. Most drugs require lower initial dosing, slow
      titration, and lower maximum dosing when used with older adults. Active screening
      by an interdisciplinary team along with appropriate interventions to address
      medication management, as well as gait, strength, and balance training, may
      reduce the risk of falls among older adults taking psychotropic medications.

PMID- 20795593
TI  - Placement of older adults from hospital mental health units into nursing homes:
      exploration of the process, system issues, and implications.
AB  - Decision making about placing older adults with mental illness and the process of
      placement from mental health units into nursing homes is challenging for older
      adults, family members, and health care professionals. In this article, I present
      an individual example drawn from an institutional ethnography examining the
      process of placement from mental health units into nursing homes in western
      Canada. I offer an analysis of the institutional processes and system issues that
      factor into the difficulties of placing this older adult with mental illness and
      suggest implications for nurses.

PMID- 20795594
TI  - Needs of older cancer survivors in a community cancer care setting.
AB  - This study describes the unique supportive care needs and associated distress
      among older adults receiving cancer survivorship care in a community cancer
      center. The psychological and social changes that accompany aging may influence
      the impact of cancer, so documenting the distinctive experiences of older
      survivors is critical to the development of evidence-based practice guidelines. A
      secondary analysis of data was conducted using results from a survey of adult
      cancer survivors. Data were available from a convenience sample of 307 survivors
      receiving care in a community cancer care setting who volunteered to complete a
      Survey of Needs. Fatigue, fear of recurrence, sleep disturbance,
      balance/walking/mobility difficulties, long-term effects of treatment, and body
      changes were most frequently reported. Results suggest assessment of older adult
      cancer survivors' experiences related to physical symptoms, symptom management,
      and interest in education targeting physical effects common to survivorship.

PMID- 20795595
TI  - The nursing home dining assistant program: a demonstration project.
AB  - The purpose of this study was to extend earlier research on the dining assistant
      (DA) federal regulation allowing trained non-nursing staff to provide feeding
      assistance care in nursing homes. Observations were conducted pre- and post
      implementation, with periodic observations during implementation. To assess
      sustainability, data were analyzed at 12 months post-implementation. Results
      replicated previous findings: DAs spent more time assisting residents, and the
      quality of care was comparable to that of nurse aides. Results confirmed
      continuation of the program at 12 months post-implementation. DA programs that
      augment nursing home staffing levels offer a feasible way to improve feeding
      assistance care within the constraints of existing resources.

PMID- 20795596
TI  - Benefits of physical activity for knee osteoarthritis: a brief review.
AB  - Osteoarthritis (OA) is the second most prevalent health condition in community
      dwelling adults 65 and older, with 27 million older Americans affected.
      Approximately half of community-dwelling women (54%) and men (43%) older than 65
      have OA, and the percentage with symptomatic knee OA rises to more than 60% among
      older adults who are overweight. This article examines major risk factors for
      knee OA and nursing interventions to help older adults with knee OA minimize
      disease symptoms. Significant health benefits of physical activity for the
      prevention of obesity, delay of onset of physical limitation, and importance to
      normal joint health for older adults with OA are emphasized. Nursing
      recommendations for physical activity in older adults with OA are detailed.
      Social and environmental barriers inhibiting older adults from achieving their
      weight loss and exercise goals are discussed. Resources supporting physical
      activity in older adults with OA are provided.

PMID- 20795597
TI  - Conversations with Holocaust survivor residents.
AB  - Traumatic events in one's younger years can have an impact on how an individual
      copes with later life. One traumatic experience for Jewish individuals was the
      Holocaust. Some of these people are moving into long-term care facilities. It was
      within this context that the research question emerged: What are Holocaust
      survivor residents' perceptions of a life lived as they move into a long-term
      care facility? For this qualitative study, Holocaust survivors were individually
      interviewed. Findings emphasize that nursing care needs to ensure that Holocaust
      survivor residents participate in activities, receive timely health care, and
      receive recognition of their life experiences.

PMID- 20795598
TI  - Fall Risk Assessment in Geriatric-Psychiatric Inpatients to Lower Events
      (FRAGILE).
AB  - The objectives of this retrospective case-control study were to identify risk
      factors of falls in geriatric-psychiatric inpatients and develop a screening tool
      to accurately predict falls. The study sample consisted of 225 geriatric
      psychiatric inpatients at a Midwestern referral facility. The sample included 136
      inpatients who fell and a random stratified sample of 89 inpatients who did not
      fall. Data collected included age, gender, activities of daily living, and
      nursing parameters such as bathing assistance, bed height, use of bed rails, one
      on-one observation, fall warning system, Conley Scale fall risk assessment,
      medical diagnosis, and medications. History of falls, impaired judgment, impaired
      gait, dizziness, delusions, delirium, chronic use of sedative or antipsychotic
      agents, and anticholinergic urinary bladder medications significantly increased
      fall risk. Alzheimer's disease, acute use of sedative or anti-psychotic agents,
      and depression reduced fall risk. A falls risk tool, Fall Risk Assessment in
      Geriatric-psychiatric Inpatients to Lower Events (FRAGILE), was developed for
      assessment and risk stratification with new diagnoses or medications.

PMID- 20795599
TI  - A comparison of hospice in the United States and the United Kingdom: implications
      for policy and practice.
AB  - The modern hospice movement in the United States was modeled on the specialized
      care for dying individuals that was championed by Dame Cicely Saunders, a social
      worker, nurse, and physician, in London in the 1960s. A collaboration between
      Saunders and Florence Wald, then at Yale University, led to the establishment of
      the first hospice in the United States in 1974. Despite similar foundations, the
      provision of hospice care differs in the United States and the United Kingdom
      with regard to financing and access. This article reviews these similarities and
      differences and discusses implications for U.S. hospice policy.

PMID- 20795600
TI  - Frequent prosthesis refitting to prevent implant exposure in patients with
      retinoblastoma.
AB  - PURPOSE: To examine the effects of prosthesis refitting on porous orbital implant
      exposure in 100 patients who underwent enucleation for retinoblastoma. METHODS:
      Parameters analyzed included patient's age at enucleation, gender, implant type,
      frequency of prosthesis adjustment, and use of chemotherapy or radiation. The
      main outcome measures consisted of the condition of the fornices, condition of
      the implant (including conjunctival thinning), and condition and functioning
      ability of the prosthesis. RESULTS: Increased frequency of visits with the
      ocularist and number of prosthesis adjustments and refits significantly improved
      the condition of the implant, fornices, and prosthesis. The patient's age at
      enucleation, gender, and use of chemotherapy or radiation did not have a
      significant effect on any of the outcome variables. The condition of the implant
      was significantly better for porous polyethylene than hydroxyapatite implants (P
      = .024). No implant exposures were observed. CONCLUSION: Frequent adjustments and
      refits by the ocularist are significantly associated with a reduced rate of
      conjunctival thinning and complete avoidance of implant exposure in patients
      undergoing enucleation for retinoblastoma. These findings are particularly
      significant for this population, which historically has demonstrated a high rate
      of implant exposure.

PMID- 20795601
TI  - Outcome study of graded unilateral medial rectus recession for small to moderate
      angle esotropia.
AB  - PURPOSE: To report an outcome study of 123 consecutive patients treated by graded
      unilateral medial rectus recession for small to moderate angle esotropia over an
      8-year period with a minimum follow-up of 6 months. METHODS: The records of
      patients who underwent unilateral medial rectus recession for constant esotropia
      measuring 15 to 35 prism diopters (PD) were reviewed. Unilateral medial rectus
      recession of 5.0, 5.5, 6.0, 6.5, and 7.0 mm was performed for 15 to 18, 19 to 20,
      21 to 25, 26 to 30, and 31 to 35 PD of esodeviation, respectively. Postoperative
      follow-up was at least 6 months. Successful alignment was defined as +/-5 PD of
      orthophoria in primary and lateral gaze while viewing distant and near
      accommodative targets. RESULTS: The eyes of 96.8% of the patients were
      successfully aligned and the average deviation corrected was 17.33 +/- 1.16 PD
      for 5 mm, 18.57 +/- 2.51 PD for 5.5 mm, 23.67 +/- 4.91 PD for 6 mm, 26.68 +/-
      3.87 PD for 6.5 mm, and 31.93 +/- 3.26 PD for 7 mm unilateral medial rectus
      recession at 6-month follow-up. Seventy-four patients (83.2%) with more than 6
      months of follow-up achieved successful alignment, 14 (15.7%) were under
      corrected, and 1 (1.1%) was overcorrected. CONCLUSION: Successful alignment was
      achieved in most esotropic patients treated by the graded unilateral medial
      rectus recessions. The surgical guidelines provide a reference for the treatment
      of small to moderate angle esotropia.

PMID- 20795602
TI  - Surgical management of adult onset age-related distance esotropia.
AB  - PURPOSE: To study the effects of bilateral medial rectus recession for the
      management of adult onset age-related distance esotropia. METHODS: Ten patients
      with adult onset age-related distance esotropia measuring 14 prism diopters or
      greater underwent bilateral medial rectus recession to eliminate the need for
      prism glasses. RESULTS: In all but one case, the diplopia completely resolved
      postoperatively, with a median residual deviation of 1 prism diopter esophoria
      for distance and 2 prism diopters exophoria at near. CONCLUSION: Bilateral medial
      rectus recession is a useful technique for the management of adult onset age
      related distance esotropia.

PMID- 20795603
TI  - Manifestations of ocular fundus in children with febrile seizures.
AB  - PURPOSE: To study the potential incidence of retinopathy in children with febrile
      seizures. METHODS: Thirty-four children with febrile seizures, aged 3 months to 9
      years and admitted from January 2000 to June 2008, were retrospectively analyzed.
      All cases received fundus examination within 24 hours after admission and the
      incidence of retinopathy was calculated. RESULTS: None of the subjects was found
      to have retinal hemorrhages. Therefore, using Hanley's Rule of Three, the upper
      limit of 95% confidence interval of retinal hemorrhages following febrile
      seizures in children is less than 10%. CONCLUSION: The incidence of retinal
      hemorrhages in children with febrile seizures is lower than 10%. If retinal
      hemorrhages are found in children with febrile seizures, other causes need to be
      considered.

PMID- 20795604
TI  - Conjunctival cysts as a complication after strabismus surgery.
AB  - PURPOSE: To identify possible factors associated with the development of a
      conjunctival cyst after surgery for strabismus. METHODS: A descriptive,
      longitudinal, and retrospective study was done including 12 cases from the past
      20 years presenting a conjunctival cyst as a complication of strabismus surgery.
      Variables included age, sex, eye and muscle operated on, surgical technique used,
      surgeon, type of suture, and type of conjunctival incision. Fisher's exact test
      and Pearson chi-square test were used for statistical analysis. RESULTS: The
      incidence of conjunctival cysts was 0.25%. Although ultimately statistically
      significant differences in the variables studied could not be demonstrated (P >
      .05), a greater incidence in the development of this complication in young
      patients who underwent recession (58.3%) as the surgical technique was observed.
      CONCLUSION: Recession may be a risk factor in the development of a conjunctival
      cyst caused by the high frequency of dragging Tenon capsule during this surgical
      technique.

PMID- 20795606
TI  - An interprofessional service-learning course: uniting students across educational
      levels and promoting patient-centered care.
AB  - Recognizing the importance of interprofessional education, we developed a pilot
      interprofessional education course at our institution that included a total of 10
      nursing, BS health psychology, premedical, and pharmacy students. Course goals
      were for students to: 1) learn about, practice, and enhance their skills as
      members of an interprofessional team, and 2) create and deliver a community-based
      service-learning program to help prevent or slow the progression of
      cardiovascular disease in older adults. Teaching methods included lecture, role
      play, case studies, peer editing, oral and poster presentation, and discussion.
      Interprofessional student teams created and delivered two different health
      promotion programs at an older adult care facility. Despite barriers such as
      scheduling conflicts and various educational experiences, this course enabled
      students to gain greater respect for the contributions of other professions and
      made them more patient centered. In addition, inter-professional student teams
      positively influenced the health attitudes and behaviors of the older adults whom
      they encountered.

PMID- 20795605
TI  - Scleral fixation of intraocular lens in eyes with history of open globe injury.
AB  - PURPOSE: To report the results and complications of scleral fixation of
      intraocular lens (SF-IOL) in traumatized eyes of children with iris defects and
      inadequate capsular support with technique customized to the condition of the
      eye. METHODS: Retrospective review of pediatric eyes with a history of open globe
      injury and SF-IOLs. All eyes had undergone pars plana vitrectomy and lensectomy
      after primary repair of the laceration. Site of scleral fixation and limbal
      incision were selected according to the site of traumatic scar, remaining
      capsular support, and keratometry. RESULTS: Ten patients with a mean age of 6.1
      years were included. Mean duration of aphakia was 18.7 months. Five eyes had
      adequate capsular support for one haptic of the IOL. The only intraoperative
      complication was mild ciliary body hemorrhage. Mean follow-up was 11.8 months.
      Uncorrected visual acuity did not improve postoperatively in only one eye due to
      severe corneal astigmatism. Best-corrected visual acuity improved in 6 eyes. Mean
      postoperative sphere and cylinder were 1.8 and -3.05 diopters, respectively. The
      only postoperative complication was decentration of a sulcus-fixed haptic needing
      reoperation in one eye. CONCLUSION: SF-IOL is a viable option for correcting
      traumatic aphakia and can have good results if customized to the condition of the
      eye.

PMID- 20795607
TI  - Great expectations: points of congruencies and discrepancies between incoming
      accelerated second-degree nursing students and faculty.
AB  - This study analyzes the expectations that incoming students and faculty bring to
      accelerated pre-licensure education programs for second-degree students. Although
      research supports the congruence of expectations between students and faculty as
      essential to learning, anecdotal evidence and single case reports suggest there
      may be important discrepancies in expectations of second-degree students and
      their faculty. Data are intended to support curriculum review, refinement, and
      innovation in these programs.

PMID- 20795609
TI  - Graduate nursing online orientation course: transitioning for success.
AB  - Graduate nursing students beginning their graduate education often lack
      technological preparedness when beginning the journey in a virtual e-learning
      environment. These gaps in preparedness include lack of understanding course
      delivery, accessing resources remotely, participating in asynchronous course
      activities, and use of emerging health care technologies. This article describes
      an educational innovative online orientation course that simulates course
      activities so that students get a true perspective of what e-learning entails.
      With enhanced education through the accelerated learning modules, students became
      proficient with distance education, which promotes success in an online master's
      of science in nursing program.

PMID- 20795608
TI  - Teaching research and evidence-based practice using a service-learning approach.
AB  - Because nurses are expected to engage in evidence-based practice (EBP), nursing
      students must learn to critically evaluate and apply research findings to prepare
      for professional practice. To connect research and EBP, the focus of a
      baccalaureate research course was changed from a traditional format to one of
      evidence appraisal and synthesis. Using an approach that incorporated service
      learning and collaborative learning resulted in a new hybrid course that provided
      students with an opportunity to apply concepts in the real world. Working with a
      community partner, students were able to develop PICO (Population, Intervention,
      Comparison, and Outcome) questions and critically appraise the literature to
      establish the evidence base for three pediatric programs. Students reported that
      working with a community partner was a meaningful experience because course
      assignments had a direct impact on current practice. Research courses taught from
      an EBP perspective can provide motivation for students to incorporate research
      into their practice as professional nurses.

PMID- 20795610
TI  - Tailoring a diabetes nursing elective course to millennial students.
AB  - Tailoring classroom teaching to millennial college students who have grown up as
      active learners is challenging. Interactive, collaborative teaching methods may
      be effective with such learners. An innovative class using Diabetes Conversation
      Maps, a patient self-management tool, was taught as an elective course. Students
      were assigned the role of a person who received a diagnosis of diabetes; the role
      included the person's specific age, gender, ethnicity, medication regimen, and
      predominant emotion. Students were expected to complete the assigned readings to
      enable them to role-play during five Conversation Map sessions. An updated,
      modified version of the Michigan Diabetes Research and Training Center's Brief
      Diabetes Knowledge Test was used to evaluate knowledge in a pretest-posttest
      format. The new teaching method resulted in an increased knowledge of diabetes
      and patient education techniques, as well as high student satisfaction.

PMID- 20795611
TI  - Ways of seeing: using the visual arts in nursing education.
AB  - Professional nursing defines its foundation of practice as embedded in the
      sciences and humanities of a liberal education. This liberal education is
      commonly alluded to with the phrase "the art and science of nursing." Yet how do
      we as nursing educators integrate these two concepts? This article describes a
      method of integrating the humanities as part of an innovative clinical
      experience. A defined visual art experience was used to improve professional
      nursing students' observational and communication skills, narrative sequencing
      abilities, and empathy. The nursing and medical literature describing the use of
      visual art encounters in health care education is reviewed. The incorporation of
      an art education program into the curriculum of a cohort of accelerated
      baccalaureate nursing students is described. Qualitative evaluation measures from
      the students suggest this was an experience that broadened their understanding of
      patient encounters.

PMID- 20795612
TI  - Academic misconduct in nursing students: behaviors, attitudes, rationalizations,
      and cultural identity.
AB  - The purpose of this study was to gain knowledge about academic misconduct in
      associate degree nursing students enrolled in two nursing programs in the
      northeastern United States. Study respondents (n = 193) identified the frequency
      of engagement in behaviors of misconduct in both the classroom and clinical
      setting and their attitudes toward the identified behaviors of misconduct,
      neutralization behaviors, ethical standards of the nursing profession, and the
      ethic of caring within the nursing profession. Findings were consistent with
      previous research on academic misconduct in baccalaureate nursing students.
      Analysis of self-reported cultural identities refuted the prevailing literature
      on academic misconduct across differing cultures and nations.

PMID- 20795613
TI  - Clinical leadership project.
AB  - Nurse educators seek innovative strategies to maximize student learning in the
      classroom and clinical settings. Students enrolled in a nursing leadership and
      management course often find they spend more clinical time observing leaders than
      practicing the necessary skills to lead others in the provision of nursing care.
      In addition, opportunities to explore the nurse educator role often do not exist
      in baccalaureate nursing education, despite the shortage of nurse educators. An
      experience was developed in a baccalaureate nursing program to give senior
      students, under supervision of faculty, the opportunity to lead and evaluate
      lower-level students providing patient care in the clinical setting and to
      experience the role of nursing faculty. Feedback from senior students was
      positive, and students noted increased proficiency in leadership ability and
      critical thinking. Student interest in the nurse educator role was also enhanced.
      Program expansion and evaluation with faculty, clinical staff, and patients are
      planned.

PMID- 20795614
TI  - Third-year undergraduate nursing students' perceptions of high-fidelity
      simulation.
AB  - High-fidelity simulation, with the potential to enhance cognitive, associative,
      and autonomous skills, can help students develop clinical reasoning. This study
      examined third-year students' (N = 300) perceptions about the implementation of
      high-fidelity simulation into an existing clinical course. Data were collected
      using an evaluation form completed by students after the simulation. Students
      perceived high-fidelity simulation as enjoyable, with an appropriate degree of
      challenge yet possessing congruency with concepts studied in the course.
      Students' transient feelings of confusion were interpreted as a natural component
      of the problem solving process as they analyzed, clustered, and interpreted cues
      to respond to rapid changes in the simulated patient's clinical condition.
      Debriefing was viewed as an important component and assisted in clarifying
      students' knowledge and rationale for practice. Further research is required on
      the relationship between the degree of confusion and its impact on learning and
      whether high-fidelity simulation increases the ability to reason in the clinical
      setting.

PMID- 20795615
TI  - It's just a saying...

PMID- 20795616
TI  - Leadership in doctoral nursing research programs.
AB  - The expansion of U.S. doctoral nursing research programs and transitions based on
      demographic distribution of the nursing academic workforce raises questions about
      the preparation for leadership transition planning. The purpose of this study was
      to describe the program leaders, job conditions, and status of transition
      efforts. A survey of U.S. nursing research doctoral programs (N = 105) was
      conducted in 2008. The response rate was 84.8%. A Web search of nonresponding
      schools provided some data from all programs. Most research doctoral program
      leaders hold additional responsibilities (mean = 4.2). The mean budgeted
      leadership time was 32.9% (SD = 21.4). Among programs in which the director's age
      was at least 60 years, 59% had no succession plan. Continuing improvement of the
      quality of doctoral nursing research programs could be compromised by leadership
      transition issues. To produce research-competitive graduates, continued support
      and attention to leadership of these programs is essential.

PMID- 20795617
TI  - Casting a vote: a creative opportunity for service-learning.

PMID- 20795618
TI  - Medical-surgical clinical make-up using a simulated laboratory experience.

PMID- 20795619
TI  - Quantum-dot-decorated robust transductable bioluminescent nanocapsules.
AB  - Bioluminescence, due to its high sensitivity, has been exploited in various
      analytical and imaging applications. In this work, we report a highly stable,
      cell-transductable, and wavelength-tunable bioluminescence system achieved with
      an elegant and simple design. Using aqueous in situ polymerization on a
      bioluminescent enzyme anchored with polymerizable vinyl groups, we obtained
      nanosized core-shell nanocapsules with the enzyme as the core and a cross-linked
      thin polymer net as the shell. These nanocapsules possess greatly enhanced
      stability, retained bioactivity, and a readily engineered surface. In particular,
      by incorporating polymerizable amines in the polymerization, we endowed the
      nanocapsules with efficient cell-transduction and sufficient conjugation sites
      for follow-up modification. Following in situ polymerization, decorating the
      polymer shell with fluorescent quantum dots allowed us to access a continuous
      tunable wavelength, which extends the application of such bioluminescent
      nanocapsules, especially in deep tissue. In addition, the unique core-shell
      structure and adequate conjugation sites on surface enabled us to maximize the
      BRET efficiency by adjusting the QD/enzyme conjugation ratio.

PMID- 20795621
TI  - Synthesis and characterization of tetraphenyl-21,23-dideazaporphyrin: the best
      evidence yet that porphyrins really are the [18]annulenes of nature.
AB  - McMurry coupling of a pyrrole bisacrylaldehyde afforded a dipyrrolic macrocycle
      that is structurally midway between 1,10-diaza[18]annulene and the porphyrins.
      The diprotonated dication of this system retains porphyrin-like properties and
      provides insights into the nature of porphyrinoid aromaticity.

PMID- 20795620
TI  - MRI detection of VEGFR2 in vivo using a low molecular weight peptoid-(Gd)8
      dendron for targeting.
AB  - The synthesis of a polylysine dendron containing eight GdDOTA units conjugated to
      a peptoid dimer known to have a high affinity for the vascular endothelial growth
      factor receptor 2 (VEGFR2) is described. This simple low molecular weight system
      with a molecular r(1) relaxivity of ~48 mM(-1) s(-1) is shown to enhance MR
      images of tumors grown in mice in vivo.

PMID- 20795622
TI  - Phenolic compounds responsible for the superoxide dismutase-like activity in high
      Brix apple vinegar.
AB  - High-Brix apple vinegar (HBAV) with palatable drinking qualities has been
      developed using a greater amount of apple ingredients. In HBAV and in regular
      apple vinegar (RAV), constituents of 4 kinds of organic acids, 20 kinds of amino
      acids, 3 kinds of sugars, 4 kinds of minerals, and phenols were determined. These
      constituents, except for acetic acid, in HBAV are of higher abundance than in
      RAV. HBAV had a 7.1 times greater superoxide dismutase (SOD)-like activity
      compared with RAV. Those constituents, except for phenols, had very low SOD-like
      activity, and total phenol levels in HBAV were comparable to 181 mg of gallic
      acid equivalents/100 mL, which was 6.0 times more abundant than in RAV. Nine
      kinds of phenols including two kinds of hydroxycinnamates, two kinds of
      hydroxybenzoates, and five kinds of hydroxycinnamoyl quinates, originating from
      raw material were determined, but there were no ascorbic acid and flavonoids in
      HBAV. Chlorogenic acid, 4-p-coumaroylquinic acid, and caffeic acid were the three
      major phenols, and their content levels were 19.6, 13.5, and 0.76 mg in 100 mL of
      HBAV, respectively. Sum of contents of chlorogenic acid and the isomers was 24.0
      mg/100 mL, and the percentage was 56.9% in the total identified phenols in HBAV.
      In RAV, only chlorogenic acid was determined as phenols, and the content was 3.1
      mg/100 mL. SOD-like activities of the constituents of HBAV were obtained through
      high-accuracy assays using vinegar reconstitutions, and each contribution to the
      total SOD-like activity was found. As a result, 77.2% for all SOD-like activity
      of HBAV was reconstituted using the determined nine phenols and other
      constituents. Chlorogenic acids were the most effective, and the contribution to
      the total activity was 41.7%. The most abundant phenols, chlorogenic acids, were
      the most important contributors to the SOD-like activity. These SOD-active
      phenols originated from raw material and remained through the acetic acid
      fermentation processes. In the fermentation process of HBAV, the active
      constituents were well maintained, providing an advantage in the production of a
      phenol-rich product.

PMID- 20795623
TI  - Highly efficient iridium-catalyzed asymmetric hydrogenation of unprotected beta
      enamine esters.
AB  - A highly efficient and enantioselective hydrogenation of unprotected beta-enamine
      esters catalyzed by Ir-(S,S)-f-Binaphane complex has been developed. This
      methodology provides straightforward access to free beta-amino acids in high
      yields with excellent enantioselectivities up to 97% ee and high reactivities
      (TON > 5000).

PMID- 20795624
TI  - Solution structure of polytheonamide B, a highly cytotoxic nonribosomal
      polypeptide from marine sponge.
AB  - Polytheonamide B (pTB), a highly cytotoxic polypeptide, is one of the most
      unusual nonribosomal peptides of sponge origin. pTB is a linear 48-residue
      peptide with alternating D- and L-amino acids and contains a total of eight types
      of nonproteinogenic amino acids. To investigate the mechanisms underlying its
      cytotoxic activity, we determined the three-dimensional structure of pTB by NMR
      spectroscopy, structure calculation, and energy minimization. pTB adopts a single
      right-handed beta(6.3)-helical structure in a 1:1 mixture of methanol/chloroform
      with a length of approximately 45 A and a hydrophilic pore of ca. 4 A inner
      diameter. These features indicate that pTB molecules form transmembrane channels
      that permeate monovalent cations as gramicidin A channels do. The strong
      cytotoxicity of pTB can be ascribed to its ability to form single molecule
      channels through biological membranes.

PMID- 20795625
TI  - Chitosan/siRNA nanoparticles biofunctionalize nerve implants and enable neurite
      outgrowth.
AB  - Microstructured 20 MUm thick polymer filaments used as nerve implants were loaded
      with chitosan/siRNA nanoparticles to promote nerve regeneration and ensure local
      delivery of nanotherapeutics. The stable nanoparticles were rapidly internalized
      by cells and did not affect cell viability. Target mRNA was successfully reduced
      by 65-75% and neurite outgrowth was enhanced even in an inhibitory environment.
      This work, thus, supports the application of nanobiofunctionalized implants as a
      novel approach for spinal cord and nerve repair.

PMID- 20795626
TI  - Ultrathin spinel LiMn2O4 nanowires as high power cathode materials for Li-ion
      batteries.
AB  - Ultrathin LiMn(2)O(4) nanowires with cubic spinel structure were synthesized by
      using a solvothermal reaction to produce alpha-MnO(2) nanowire followed by solid
      state lithiation. LiMn(2)O(4) nanowires have diameters less than 10 nm and
      lengths of several micrometers. Galvanostatic battery testing showed that
      LiMn(2)O(4) nanowires deliver 100 and 78 mAh/g at very high rate (60C and 150C,
      respectively) in a larger potential window with very good capacity retention and
      outstanding structural stability. Such performances are due to both the favorable
      morphology and the high crystallinity of nanowires.

PMID- 20795627
TI  - Particle size dependence of the ionic diffusivity.
AB  - Diffusion constants are typically considered to be independent of particle size
      with the benefit of nanosizing materials arising solely from shortened transport
      paths. We show that for materials with one-dimensional atomic migration channels,
      the diffusion constant depends on particle size with diffusion in bulk being much
      slower than in nanoparticles. This model accounts for conflicting data on
      LiFePO(4), an important material for rechargeable lithium batteries, specifically
      explaining why it functions exclusively on the nanoscale.

PMID- 20795628
TI  - Bronsted acid catalyzed cyclization of propargylic alcohols with thioamides.
      Facile synthesis of di- and trisubstituted thiazoles.
AB  - A general and efficient method to prepare 2,4-di- and trisubstituted thiazoles
      via p-TsOH.H(2)O-catalyzed cyclization of trisubstituted propargylic alcohols
      with thioamides is described. The reaction was accomplished in moderate to
      excellent product yields under mild conditions that did not require the exclusion
      of air and moisture and offers an operationally simplistic and convenient route
      to this synthetically useful aromatic heterocycle.

PMID- 20795629
TI  - Coupled nanoantenna plasmon resonance spectra from two-photon laser excitation.
AB  - We report on the two-photon excitation and subsequent plasmonic mode relaxation
      of coupled optical gold nanoantennas. Using pulsed laser excitation at a constant
      wavelength of 810 nm, we observe two-photon-induced plasmon emission spectra,
      find them to match dark-field microscopy scattering spectra, and show that the
      emission intensity is enhanced by up to a factor of 65 compared to single gold
      rods of equal dimensions. This study shows the link of nonlinear optical
      excitation schemes with radiative relaxation pathways that match plasmonic mode
      emission of resonant optical gold antennas.

PMID- 20795630
TI  - Heteroepitaxial decoration of Ag nanoparticles on Si nanowires: a case study on
      Raman scattering and mapping.
AB  - Metallic nanoparticle-decorated silicon nanowires showed considerable promise in
      a wide range of applications such as photocatalytic conversion, surface-enhanced
      Raman scattering, and surface plasmonics. However there is still insufficient
      amount of Raman scattering in Si nanowires with such decoration. Here we report
      the heteroepitaxial growth of Ag nanoparticles on Si nanowires by a surface
      reduction mechanism. The as-grown Ag nanoparticles exhibited highly single
      crystallinity with a most probable diameter of 25 nm. Raman scattering
      spectroscopy showed a new sideband feature at 495 cm(-1) below the first order Si
      transverse optical Raman peak due to HF etching. This new feature sustained after
      sequential surface treatments and rapid thermal annealing, therefore was
      attributed to polycrystalline defect at subsurface, which was confirmed by high
      resolution transmission electron microscopy observations. Correlated atomic force
      microscopy and Raman mapping demonstrated that single Ag nanoparticle decoration
      significantly enhanced Raman signal of Si nanowire by a factor of 7, suggesting
      that it would be a promising approach to probe phonon confinement and radial
      breathing mode in individual nanowires down to sub-10 nm regime.

PMID- 20795633
TI  - Dynamic wetting of non-newtonian fluids: multicomponent molecular-kinetic
      approach.
AB  - Hydrodynamic models are generally applied to describe the dynamic wetting of
      newtonian or non-newtonian fluids on a solid surface. Conversely, the molecular
      kinetic paradigm is only utilized for spreading newtonian fluids while
      considering the movement of a contact line as a molecular hopping process. This
      study extended the molecular-kinetic paradigm to the wetting behavior of non
      newtonian fluids, while assuming there are n fluid components at the contact line
      regime interacting simultaneously with a solid surface during front movement. The
      limiting cases of the derived model at slow and fast moving speeds were
      discussed. Moreover, the derived model was validated based on dynamic contact
      angle data of three carboxymethylcellulose (CMC) aqueous solutions measured using
      the force-balance method. Best-fit parameters were used to interpret the wetting
      dynamics of CMC solutions.

PMID- 20795631
TI  - Binding of the dimeric Deinococcus radiodurans single-stranded DNA binding
      protein to single-stranded DNA.
AB  - Deinococcus radiodurans single-stranded (ss) DNA binding protein (DrSSB)
      originates from a radiation-resistant bacterium and participates in DNA
      recombination, replication, and repair. Although it functions as a homodimer, it
      contains four DNA binding domains (OB-folds) and thus is structurally similar to
      the Escherichia coli SSB (EcoSSB) homotetramer. We examined the equilibrium
      binding of DrSSB to ssDNA for comparison with that of EcoSSB. We find that the
      occluded site size of DrSSB on poly(dT) is ~45 nucleotides under low-salt
      conditions (<0.02 M NaCl) but increases to 50-55 nucleotides at >=0.2 M NaCl.
      This suggests that DrSSB undergoes a transition between ssDNA binding modes,
      which is observed for EcoSSB, although the site size difference between modes is
      not as large as for EcoSSB, suggesting that the pathways of ssDNA wrapping differ
      for these two proteins. The occluded site size corresponds well to the contact
      site size (52 nucleotides) determined by isothermal titration calorimetry (ITC).
      Electrophoretic studies of complexes of DrSSB with phage M13 ssDNA indicate the
      formation of stable, highly cooperative complexes under low-salt conditions.
      Using ITC, we find that DrSSB binding to oligo(dT)s with lengths close to the
      determined site size (50-55 nucleotides) is stoichiometric with a DeltaH(obs) of
      approximately -94 +/- 4 kcal/mol, somewhat smaller than that for EcoSSB
      (approximately -130 kcal/mol) under the same conditions. The observed binding
      enthalpy shows a large sensitivity to NaCl concentration, similar to that
      observed for EcoSSB. With the exception of the less dramatic change in occluded
      site size, the behavior of DrSSB is similar to that of EcoSSB protein (although
      clear quantitative differences exist). These common features for SSB proteins
      having multiple DNA binding domains enable versatility of SSB function in vivo.

PMID- 20795632
TI  - Synthesis of a lactone diastereomer of the cembranolide uprolide D.
AB  - A convergent stereoselective synthesis of a C1/C14 bis-epimer of uprolide D is
      described in which an intramolecular Barbier-type reaction was employed for
      macrocyclization with concomitant introduction of the C1 and C14 stereocenters of
      a fused alpha-methylene lactone ring through an anti-Felkin-Anh transition state.
      Unlike previous examples of allyl chromium additions, none of the Felkin-Anh
      derived adduct could be detected.

PMID- 20795634
TI  - Synthesis of symmetrical and unsymmetrical diarylalkynes from propiolic acid
      using palladium-catalyzed decarboxylative coupling.
AB  - Symmetrical diarylalkynes were obtained from propiolic acid (or 2-butynedioic
      acid) and aryl halides in good yields. The optimized reaction conditions were 2.0
      equiv of aryl halide, 1.0 equiv of propiolic acid, 5.0 mol % Pd(PPh(3))(2)Cl(2),
      10.0 mol % 1,4-bis(diphenylphosphino)butane (dppb), 2.0 equiv of 1,8
      diazabicyclo[5.4.0]undec-7-ene (DBU), and dimethyl sulfoxide (DMSO) as the
      solvent. The coupling reaction of 2-butynedioic acid with aryl halides required
      110  degrees C. The coupling reaction showed tolerance for functional groups such
      as ester, ketone, and aldehyde and exhibited chemoselectivity. In the coupling
      reaction of propiolic acid with aryl bromide, the diarylated product was the
      major one at 80  degrees C, even though 1 equiv of aryl halides was employed.
      However, among the monoarylated products that were formed predominantly at 25 and
      50  degrees C in the coupling reaction with aryl iodide, more Sonogashira
      coupling product was obtained than the decarboxylative coupling product.
      Unsymmetrical diarylalkynes were also synthesized via this method, in which all
      reagents, including propiolic acid, aryl iodide, and aryl bromides were added at
      the beginning of the reaction.

PMID- 20795635
TI  - Mass spectrometry-based fragmentation as an identification tool in lignomics.
AB  - The ensemble of all phenolics for which the biosynthesis is coregulated with
      lignin biosynthesis, i.e., metabolites from the general phenylpropanoid,
      monolignol, and (neo)lignan biosynthetic pathways and their derivatives, as well
      as the lignin oligomers, is coined the lignome. In lignifying tissues, the
      lignome comprises a significant portion of the metabolome. However, as is true
      for metabolomics in general, the structural elucidation of unknowns represents
      the biggest challenge in characterizing the lignome. To minimize the necessity to
      purify unknowns for NMR analysis, it would be desirable to be able to extract
      structural information from liquid chromatography-mass spectrometry data
      directly. However, mass spectral libraries for metabolomics are scarce, and no
      libraries exist for the lignome. Therefore, elucidating the gas-phase
      fragmentation behavior of the major bonding types encountered in lignome
      associated molecules would considerably advance the systematic characterization
      of the lignome. By comparative MS(n) analysis of a series of molecules belonging
      to the beta-aryl ether, benzodioxane, phenylcoumaran, and resinol groups, we
      succeeded in annotating typical fragmentations for each of these bonding
      structures as well as fragmentations that enabled the identification of the
      aromatic units involved in each bonding structure. Consequently, this work lays
      the foundation for a detailed characterization of the lignome in different plant
      species, mutants, and transgenics and for the MS-based sequencing of lignin
      oligomers and (neo)lignans.

PMID- 20795637
TI  - Identifying and quantifying contaminants contributing to endogenous analytes in
      gas chromatography/mass spectrometry.
AB  - Contaminants from various sources including medical devices, laboratory materials
      and the environment, and analytical apparatus may contribute to their endogenous
      congeners at different stages of the analytical process. Here, an approach is
      reported for the identification and quantification of contaminating analytes in
      biological fluids by stable-isotope dilution gas chromatography/mass spectrometry
      (GC/MS) and gas chromatography/tandem mass spectrometry (GC/MS/MS) methods. This
      approach is based on the analysis of different sample volumes and determination
      of the peak area ratio (PAR) of the endogenous analyte to the stable-isotope
      labeled analogue serving as the internal standard. The PAR is obtained by
      selected-ion monitoring or selected-reaction monitoring of appropriate ions.
      Generation of PAR values that correlate inversely with the sample volume
      subjected to analysis reveals the existence of contamination. The extent of
      contamination is obtained by plotting the PAR of endogenous analyte to internal
      standard versus the reciprocal of the sample volume analyzed. Examples are given
      for uncontaminated and contaminated endogenous analytes in biological samples,
      including nitrite and nitrate analyzed by GC/MS, and the fatty acid metabolites
      oleic acid oxide, oleic acid ethanol amide, and arachidonic acid ethanol amide
      analyzed by GC/MS/MS. Dependence of the PAR of endogenous analyte to its internal
      standard upon derivatization time reveals a unique kind of contamination that was
      identified in the GC/MS analysis of nitrate in plasma as pentafluorobenzyl ester.
      This kind of contamination occurs at the latest stage of GC/MS analysis and
      cannot be controlled by reference to the internal standard.

PMID- 20795636
TI  - Dansylation of unactivated alcohols for improved mass spectral sensitivity and
      application to analysis of cytochrome P450 oxidation products in tissue extracts.
AB  - Chemical derivatization is useful for improving the ionization characteristics of
      poorly or nonionizable analytes in liquid chromatography-mass spectrometry (LC
      MS). Dansyl chloride has been widely used as a derivatizing reagent for
      fluorescence detection and for facilitating the MS detection of phenols and
      amines, but not for general alcohols. A new dansylation method for improving the
      mass spectral sensitivity of unactivated alcohols was developed. The dansylated
      derivative was formed after incubation of the test compound cholesterol and
      excess dansyl chloride in CH(2)Cl(2) in the presence of 4-(dimethylamino)
      pyridine (DMAP) plus N,N-diisopropylethylamine at 65  degrees C for 1 h, with an
      overall yield of 96%. The versatility of dansylation was investigated by
      utilizing representative lipid compounds (containing different numbers of hydroxy
      groups) for dansylation. All dansylated derivatives of the selected compounds
      were detected by LC-MS/MS in the electrospray ionization (ESI) positive ion mode.
      Validation of the method was established in terms of the sensitivity, stability,
      and repeatability of dansylation. The method was then applied to characterizing
      the P450 7A1 oxidation product (dansylated 7alpha-hydroxycholesterol) in human
      liver extracts using an LC-MS metabolomics/isotopic labeling approach (Tang, Z.;
      Guengerich, F. P. Anal. Chem. 2009, 81, 3071-3078). The dansylated derivative of
      the product was identified, with the signal increased by 10(3)-fold compared with
      a previous method (derivatization with succinic anhydride and ESI negative ion
      MS). Quantitation of testosterone in human liver extracts was also done as an
      example of the application of the dansylation method. Thus, dansylation is a
      potential method of modifying many alcohols for detection by fluorescence and LC
      MS analysis.

PMID- 20795638
TI  - Fine tuning of the relaxometry of gamma-Fe2O3@SiO2 nanoparticles by tweaking the
      silica coating thickness.
AB  - We report the fine-tuning of the relaxometry of gamma-Fe2O3@SiO2 core-shell
      nanoparticles by adjusting the thickness of the coated silica layer. It is clear
      that the coating thickness of Fe2O3@SiO2 nanoparticles has a significant impact
      on the r(1) (at low B0 fields), r(2), and r(2)* relaxivities of their aqueous
      suspensions. These studies clearly indicate that the silica layer is
      heterogeneous and has regions that are porous to water and others-that are not.
      It is also shown, that the viability and the mitochondrial dehydrogenase
      expression of the microglial cells do not appear to be sensitive to the vesicular
      load with these core-shell nanoparticles. The adequate silica-shell thickness can
      therefore be tuned to allow for both a sufficiently high response as contrast
      agent, and-adequate grafting of targeted biomolecules.

PMID- 20795639
TI  - Novel amidinating cross-linker for facilitating analyses of protein structures
      and interactions.
AB  - A novel bifunctional thioimidate cross-linking reagent (diethyl suberthioimidate)
      that modifies amines without sacrificing their native basicity is developed.
      Intermolecular cross-linking of neurotensin and intramolecular cross-linking of
      cytochrome c under physiological conditions is investigated with this reagent.
      Because it does not perturb the electrostatic properties of a protein, it is
      unlikely to lead to artifactual conclusions about native protein structure. The
      interpeptide cross-links formed with this reagent are easily separated from other
      tryptic fragments using strong cation exchange chromatography, and they have a
      readily identified mass spectrometric signature. The use of this novel
      amidinating protein cross-linking reagent holds great promise for efficient,
      large-scale structural analysis of complex systems.

PMID- 20795640
TI  - In-gel digestion for mass spectrometric characterization of RNA from
      fluorescently stained polyacrylamide gels.
AB  - Although current mass spectrometry-based proteomics technology allows for high
      throughput analysis of protein components in functional ribonucleoprotein
      complexes, this technology has had limited application to studies of RNA itself.
      Here we present a protocol for RNA analysis using polyacrylamide gel
      electrophoresis coupled with liquid chromatography-tandem mass spectrometry.
      Specifically, RNAs of interest are subjected to polyacrylamide gel
      electrophoresis and stained with a fluorescent dye, and RNAs in gel bands are
      digested with nuclease and then analyzed directly liquid chromatography-mass
      spectrometry, resulting in highly accurate mass values and reliable information
      on post-transcriptional modifications. We demonstrate that the method can be
      applied to the identification and chemical analysis of small RNAs in mouse
      embryonic stem cell extracts and of small RNAs in the spliceosomal
      ribonucleoprotein complex pulled down from yeast cells using a tagged protein
      cofactor as bait. The protocol is relatively simple and allowed us to identify
      not only three novel methylated nucleotide residues of RNase P RNA, U6 snRNA, and
      7SL RNA prepared from mouse ES cells but also various 3'-end forms of U4, U5S,
      and U6 snRNAs isolated from the yeast spliceosome at the femtomole level. The
      method is thus a convenient tool for direct analysis of RNAs in various cellular
      ribonucleoprotein complexes, particularly for the analysis of post
      transcriptional modifications and metabolic processing of RNA.

PMID- 20795642
TI  - Monomeric square-planar cobalt(II) acetylacetonate: mystery or mistake?
AB  - No evidence was found for the existence of a previously reported mononuclear
      square-planar form of unsolvated cobalt(II) acetylacetonate, Co(acac)(2), in all
      samples that have been obtained by using a variety of preparative techniques and
      crystallization conditions. It was confirmed that the structure of tetramer
      Co(4)(acac)(8), reported back in 1964 by Cotton and Elder, is correct, the
      synthesis is reproducible, and the bulk material corresponds to single-crystal
      data. Additionally, the title compound can be isolated in tetranuclear form by
      reducing cobalt(III) acetylacetonate with cobalt metal in solvent-free conditions
      or by crystallization from a hexanes solution. At the same time, from
      noncoordinating halogenated solvents, Co(acac)(2) crystallizes as a trinuclear
      core molecule, in which all Co atoms also exhibit octahedral coordination. From
      coordinating solvents such as ethanol, cobalt(II) acetylacetonate was found to
      appear in the form of its bis-adduct Co(acac)(2)(EtOH)(2). On the basis of
      observations made in this work and the details presented in the original paper,
      we suggest that the reported mononuclear structure of square-planar
      acetylacetonate should likely contain copper instead of cobalt.

PMID- 20795641
TI  - An approach to quantifying N-linked glycoproteins by enzyme-catalyzed 18O3
      labeling of solid-phase enriched glycopeptides.
AB  - Global analysis of glycoproteins shows great promise for the discovery of
      therapeutic targets and clinical biomarkers. Selective capture of glycopeptides
      by hydrazide resin followed by mass spectrometric identification of the peptides
      released by PNGaseF treatment has been most widely used. However, the majority of
      the reports using this approach focus on global profiling, rather than relative
      quantitation of glycoprotein alternations in pathological states. We describe an
      integrated strategy allowing for relative quantitation of glycoproteins in
      complex biological mixtures using this approach. The strategy includes periodate
      oxidation of tryptic digests, solid-phase enrichment of glycopeptides via
      hydrazide-coupled magnetic beads, in conjunction with (18)O stable isotope
      labeling catalyzed by both trypsin and PNGaseF, and subsequent identification and
      quantitation by LC-MS/MS analysis. Three (18)O atoms ((18)O(3)) are incorporated
      into N-linked glycopeptides for samples treated in (18)O-water, two at the
      carboxyl terminus by trypsin during hydrazide coupling and the third at the N
      glycosylation site through PNGaseF-mediated deglycosylation. Thus, mass shifts of
      6 and 8 Da are indicative of singly and doubly glycosylated peptides,
      respectively. Experimental conditions were optimized to promote the trypsin
      mediated (18)O(2) incorporation and prevent backbone exchange. The accuracy,
      reproducibility, and linearity of relative quantitation were evaluated by using
      15 glycoproteins spiked into mouse serum at different concentration ratios. Using
      this approach, we were able to identify and quantitate 224 N-glycopeptides
      representing 130 unique glycoproteins from 20 MUL of the undepleted mouse serum
      samples. The strategy can be easily adapted to the analysis of glycoproteins in
      tissues, cell lines, and other sample origins.

PMID- 20795643
TI  - Mixed d-f3 coordination complexes possessing improved near-infrared (NIR)
      lanthanide luminescent properties in aqueous solution.
AB  - The cyclen-based ligand 1, possessing a [1,10]-phenanthroline moiety as a pendant
      arm, has been used as a ditopic ligand for the complexation of d- and near
      infrared (NIR) emitting (and) f-metal ions. This ligand forms kinetically stable
      complexes, 1.Ln, with lanthanide ions such as Ln = ytterbium, neodymium, and
      lutetium (formed as a non-IR emitting reference compound), the synthesis and
      photophysical properties of which are described herein in detail. These 1.Ln
      complexes were then used as building blocks for the formation of mixed d-f
      heteropolymetallic self-assemblies, where the phen moiety was used to complex a
      ruthenium (Ru(II)) ion, giving the d-f3 complexes Ru.Ln3 (Ln = Nd(III), Yb(III),
      Lu(III)). The formation of these supramolecular coordination conjugates was
      studied by using absorption and luminescence spectroscopy, while the solution
      structure of the Ru.Lu3 was elucidated by 1H NMR in D2O and H2O. Of these
      conjugates, both Ru.Nd3 and Ru.Yb3 displayed an intense NIR-emission in H2O at pH
      7.4 (with Q(Yb)(L) = 0.073% and Q(Nd)(L) = 0.040%) and in D2O (with QYbL = 0.23%
      and Q(Nd)(L) = 0.10%). By comparison with their monometallic analogues Ln.1 (Ln =
      Nd(III), Yb(III)), we demonstrate that our new design possesses an enhanced
      sensitization efficiency for lanthanide metal centered sensitization upon using
      the [Ru(phen)3] moiety (d -> f energy transfer) as a visibly exciting antenna,
      and we demonstrate that the intensity of the Ru(II)-based luminescence strictly
      correlates to the efficiency of the d -> f energy transfer processes.

PMID- 20795644
TI  - Label-free detection of proteins from self-assembled protein-silver nanoparticle
      structures using surface-enhanced Raman scattering.
AB  - Proteins are one of the most versatile groups of molecules with vital functional
      roles in living systems. Their enormous diversity and structural flexibility make
      the detection of these molecules a challenging task. A simple and sensitive label
      free protein detection method based on assembly of proteins and colloidal silver
      nanoparticles (AgNPs) on surfaces and surface-enhanced Raman scattering (SERS) is
      reported. The SERS spectra from the assembled AgNP/protein films show excellent
      reproducibility and high quality regardless of the proteins' charge status and
      size. A detection limit down to 0.5 MUg/mL for three acidic proteins; BSA,
      catalase and pepsin, and three basic proteins; cytochrome c, avidin and lysozyme,
      is easily achieved. The minimum improvement in detection limit is more than 1
      order of magnitude compared to the previously reported detection limits using the
      technique and the approach has the potential for label-free protein detection and
      identification.

PMID- 20795645
TI  - Mixed azide and 5-(pyrimidyl)tetrazole bridged Co(II)/Mn(II) polymers: synthesis,
      crystal structures, ferroelectric and magnetic behavior.
AB  - The reaction of pyrimidine-2-carbonitrile, NaN(3) in the presence of
      Co(NO(3))(2).6H(2)O or MnCl(2).4H(2)O leads to the formation of complexes
      [Co(pmtz)(MU(1,3)-N(3))(H(2)O)](n) (1) and [Mn(pmtz)(MU(1,3)-N(3))(H(2)O)](n) (2)
      respectively, under hydrothermal condition [pmtz = 5-(pyrimidyl)tetrazolate].
      These two complexes have been fully characterized by single crystal X-ray
      diffraction. Complex 1 crystallizes in a non-centrosymmetric space group Aba2 in
      the orthorhombic system and is found to exhibit ferroelectric behavior, whereas
      complex 2 crystallizes in the P2(1)/c space group in the monoclinic system.
      Variable temperature magnetic characterizations in the temperature range of 2-300
      K indicate that complex 1 is a canted antiferromagnet (weak ferromagnet) with
      T(c) = 15.9 K. Complex 1 represents a unique example of a multiferroic
      coordination polymer containing tetrazole as a co-ligand. Complex 2 is a one
      dimensional chain of Mn(II) bridged by a well-known antiferromagnetic coupler end
      to-end azido ligand. In contrast to the role played by the end-to-end azido
      pathway in most of the transition metal complexes, complex 2 showed unusual
      ferromagnetic behavior below 40 K because of spin canting.

PMID- 20795646
TI  - Mossbauer, electron paramagnetic resonance, and density functional theory studies
      of synthetic S = 1/2 Fe(III)-O-Fe(IV)?O complexes. Superexchange-mediated spin
      transition at the Fe(IV)?O site.
AB  - Previously we have characterized two high-valent complexes [LFe(IV)(MU
      O)(2)Fe(III)L], 1, and [LFe(IV)(O)(MU-O)(OH) Fe(IV)L], 4. Addition of hydroxide
      or fluoride to 1 produces two new complexes, 1-OH and 1-F. Electron paramagnetic
      resonance (EPR) and Mossbauer studies show that both complexes have an S = 1/2
      ground state which results from antiferromagnetic coupling of the spins of a high
      spin (S(a) = 5/2) Fe(III) and a high-spin (S(b) = 2) Fe(IV) site. 1-OH can also
      be obtained by a 1-electron reduction of 4, which has been shown to have an
      Fe(IV)?O site. Radiolytic reduction of 4 at 77 K yields a Mossbauer spectrum
      identical to that observed for 1-OH, showing that the latter contains an
      Fe(IV)?O. Interestingly, the Fe(IV)?O moiety has S(b) = 1 in 4 and S(b) = 2 in 1
      OH and 1-F. From the temperature dependence of the S = 1/2 signal we have
      determined the exchange coupling constant J (H = JS(a).S(b) convention) to be 90
      +/- 20 cm(-1) for both 1-OH and 1-F. Broken-symmetry density functional theory
      (DFT) calculations yield J = 135 cm(-1) for 1-OH and J = 104 cm(-1) for 1-F, in
      good agreement with the experiments. DFT analysis shows that the S(b) = 1 -> S(b)
      = 2 transition of the Fe(IV)?O site upon reduction of the Fe(IV)-OH site to high
      spin Fe(III) is driven primarily by the strong antiferromagnetic exchange in the
      (S(a) = 5/2, S(b) = 2) couple.

PMID- 20795647
TI  - Matrix metalloproteinase 9 targeting peptides: syntheses, 68Ga-labeling, and
      preliminary evaluation in a rat melanoma xenograft model.
AB  - Biopanning of tumor cells was used in order to identify matrix metalloproteinase
      9 (MMP-9) targeting peptides. The tumor cell targeting peptide (TCTP-1) and two
      modified versions thereof were evaluated as imaging agents for positron emission
      tomography (PET) using a rat melanoma xenograft model. For the PET imaging
      purposes, the 3 peptides were 1,4,7,10-tetraazacyclo-dodecane-N',N'',N''',N''''
      tetraacetic acid (DOTA) conjugated and labeled with Gallium-68 ((68)Ga) and
      preliminarily evaluated: (1) cyclic (68)Ga-DOTA-TCTP-1 with cystine bridge, (2)
      cyclic (68)Ga-DOTA-lactam-TCTP-1 with a lactam bridge, and (3) linear (68)Ga-DOTA
      lin-TCTP-1. The whole-body distribution kinetics and tumor targeting of the
      intravenously administered (68)Ga-DOTA-peptides were evaluated in vivo by PET and
      ex vivo by measuring the radioactivity of excised tissues. In addition, the in
      vivo stability of the radiolabeled peptides in rat plasma, tumor tissue, and
      urine was studied. All (68)Ga-DOTA-peptides were cleared via the liver and
      kidneys, and approximately 44% of injected radioactivity was excreted in urine
      during 120 min after injection. Ex vivo biodistribution studies showed a tumor-to
      muscle ratio of 5.5 +/- 1.3 (mean +/- SD) for (68)Ga-DOTA-TCTP-1, 3.2 +/- 0.2 for
      (68)Ga-DOTA-lactam-TCTP-1, and 3.2 +/- 0.6 for (68)Ga-DOTA-lin-TCTP-1 at 120 min
      after injection. The (68)Ga-DOTA-lactam-TCTP-1 peptide appeared to be the most
      stable in vivo. The fraction of intact (68)Ga-DOTA-lactam-TCTP-1 in tumor was 59
      +/- 4.2% at 120 min after injection. The stability was moderate for (68)Ga-DOTA
      TCTP-1 and poor for (68)Ga-DOTA-lin-TCTP-1. The possibility of imaging tumors
      that overexpress MMP-9, such as melanoma, by using radiolabeled TCTP peptides in
      PET imaging makes these peptides highly attractive for diagnostic and therapeutic
      applications. However, further modifications to improve the stability and
      affinity of the peptides are needed.

PMID- 20795649
TI  - Improving the high-performance inductively coupled plasma optical emission
      spectrometry methodology through exact matching.
AB  - Exact matching is investigated as a means of improving high-performance
      inductively coupled plasma optical emission spectrometry (HP-ICP-OES), a
      technique developed at the National Institute of Standards and Technology (NIST)
      to enable elemental determinations with relative expanded uncertainty of
      approximately 0.2% expressed at 95% confidence. "Exact matching" refers to the
      very careful matching of analyte mass fractions, internal standard mass
      fractions, and matrix compositions among the calibration and unknown sample
      solutions prepared for an analysis. Computer spreadsheet modeling results and
      laboratory data involving 16 pairs of analyte and internal standard wavelengths
      show that exact matching of analyte and internal standard mass fractions
      mitigates imprecision and bias that can be caused by even subtle nonlinearity in
      the ICP-OES instrument response. Laboratory experiments also demonstrate matrix
      effects caused by small variations in acid composition and by mass fractions of
      Na less than 4 mg kg(-1), emphasizing the need for exact matching of matrix
      compositions. HP-ICP-OES analyses performed at NIST with and without exact
      matching illustrate that exact matching enables relative expanded uncertainties
      to be halved to approximately 0.1%.

PMID- 20795648
TI  - Design, synthesis, and preliminary biological evaluation of new isoform-selective
      f-current blockers.
AB  - New I(f) blockers have been designed and tested on HEK293 cells stably expressing
      the HCN1, HCN2, and HCN4 channels to find compounds able to discriminate among
      the channel isoforms. Among the synthesized compounds, the cis-butene derivative
      (R)-5 shows some preference for HCN2 while the pseudodimeric product (R)-6 shows
      selectivity for HCN1. These compounds can be important pharmacological tools to
      study the channels in native tissues and may be useful to design safe drugs.

PMID- 20795650
TI  - Influencing solvent miscibility and aqueous stability of aluminum nanoparticles
      through surface functionalization with acrylic monomers.
AB  - With growing interest in the development of new composite systems for a variety
      of applications that require easily processable materials and adequate structural
      properties with high energy densities, we have pursued the chemical
      functionalization of oxide-passivated aluminum nanoparticles (nAl) using three
      acrylic monomers, 3-methacryloxypropyltrimethoxysilane (MPS), 2-carboxyethyl
      acrylate (CEA), and phosphonic acid 2-hydroxyethyl methacrylate ester (PAM), to
      provide chemical compatibility within various solvent and polymeric systems.
      Fourier transform infrared and X-ray photoelectron spectroscopy suggest that
      attachment of MPS and PAM monomers occurs through the formation of bonds directly
      to the passivated oxide surface upon reaction with surface hydroxyls, whereas CEA
      monomers interact through the formation of ionic carboxylate binding to aluminum
      atoms within the oxide. The coated particles demonstrate enhanced miscibility in
      common organic solvents and monomers; MPS and PAM coatings are additionally shown
      to inhibit oxidation of the aluminum particles when exposed to aqueous
      environments at room temperature, and PAM coatings are stable at even elevated
      temperatures.

PMID- 20795651
TI  - Near-infrared laser desorption/ionization aerosol mass spectrometry for
      investigating primary and secondary organic aerosols under low loading
      conditions.
AB  - A new method, near-infrared laser desorption/ionization aerosol mass spectrometry
      (NIR-LDI-AMS), is described for the real time analysis of organic aerosols at
      atmospherically relevant mass loadings. Use of a single NIR laser pulse to
      vaporize and ionize particle components deposited on an aluminum probe results in
      minimal fragmentation to produce exclusively intact pseudomolecular anions at [M
      H](-). Limits of detection (total particulate mass sampled) for oxidized
      compounds of relevance to atmospheric primary and secondary organic aerosol range
      from 89 fg for pinic acid to 8.8 pg for cholesterol. NIR-LDI-AMS was used in
      conjunction with the University of Vermont Environmental Chamber to study
      secondary organic aerosol (SOA) formation from ozonolysis of limonene at total
      aerosol mass loadings ranging from 3.2 to 25.0 MUg m(-3) and with a time
      resolution of several minutes. NIR-LDI-AMS permitted direct delineation between
      gas-phase, homogeneous SOA formation and subsequent heterogeneous aerosol
      processing by ozone.

PMID- 20795652
TI  - Competitive and noncompetitive binding of eIF4B, eIF4A, and the poly(A) binding
      protein to wheat translation initiation factor eIFiso4G.
AB  - Eukaryotic translation initiation factor 4G (eIF4G) functions to organize the
      assembly of initiation factors required for the recruitment of a 40S ribosomal
      subunit to an mRNA and for interacting with the poly(A) binding protein (PABP).
      Many eukaryotes express two highly similar eIF4G isoforms. eIFiso4G, one of two
      isoforms in plants, is highly divergent and unusually small in size. Unlike
      animal and yeast eIF4G, the domain organization of plant eIF4G proteins is
      largely unknown. Consequently, little is known about the conservation of plant
      eIF4G with those in other eukaryotes. In this study, we show that eIFiso4G is
      similar to other eIF4G proteins in that there are interaction domains for eIF4A
      and PABP and we identify, for the first time, the interaction domain for eIF4B.
      In contrast to previous reports, two eIF4A binding domains in eIFiso4G were
      identified, similar in number and organization to those of animal eIF4G. The
      eIFiso4G domain organization does differ, however, in that the N-terminal eIF4A
      binding domain overlaps with the eIF4B and PABP binding domains. Moreover, the
      eIF4B and PABP binding domains overlap. PABP and eIF4B compete with eIF4A for
      binding eIFiso4G in the absence of the C-terminal eIF4A binding domain but not
      when both eIF4A binding domains are present, suggesting that the C-terminal eIF4A
      interaction domain functions to stabilize the association of eIF4A with eIFiso4G
      in the presence of eIF4B or PABP. Competitive binding to eIFiso4G was also
      observed between eIF4B and PABP. These observations reveal an important function
      of the C-terminal eIF4A binding domain in maintaining the interaction of multiple
      partner proteins with eIFiso4G despite the substantial divergence in its size and
      domain organization.

PMID- 20795653
TI  - Base-promoted reaction of 5-hydroxyuracil derivatives with peroxyl radicals.
AB  - Addition of millimolar amounts of a weak base (pyridines) dramatically
      accelerates the reaction with peroxyl radicals of two biologically relevant
      uracil derivatives, 5-hydroxyuracil (HU) and 5-hydroxy-6-methyluracil (HMU). This
      is due to the formation of small amounts of the deprotonated form (pK(a) = 8.1
      8.5 in water), which reacts with peroxyl radicals much faster than the parent
      undissociated form, via formal H-atom transfer from the OH in the 5 position.

PMID- 20795654
TI  - DNA binding induces dimerization of Saccharomyces cerevisiae Pif1.
AB  - In Saccharomyces cerevisiae, Pif1 is involved in a wide range of DNA
      transactions. It operates both in mitochondria and in the nucleus, where it has
      telomeric and non-telomeric functions. All of the activities of Pif1 rely on its
      ability to bind to DNA. We have determined the mode of Pif1 binding to different
      DNA substrates. While Pif1 is a monomer in solution, we show that binding of
      ssDNA to Pif1 induces protein dimerization. DNA-induced dimerization of Pif1 is
      also observed on tailed- and forked-dsDNA substrates, suggesting that on the
      latter formation of a Pif1 dimer prevents binding of additional Pif1 molecules. A
      dimer of Pif1 also forms on ssDNA of random composition and in the presence of
      saturating concentrations of nonhydrolyzable ATP analogues. The observation that
      a Pif1 dimer is formed on unwinding substrates in the presence of ATP analogues
      suggests that a dimeric form of the enzyme might constitute the pre-initiation
      complex leading to its unwinding activity.

PMID- 20795655
TI  - On resonant scatterers as a factor limiting carrier mobility in graphene.
AB  - We show that graphene deposited on a substrate has a non-negligible density of
      atomic scale defects. This is evidenced by a previously unnoticed D peak in the
      Raman spectra with intensity of ~1% with respect to the G peak. We evaluated the
      effect of such impurities on electron transport by mimicking them with hydrogen
      adsorbates and measuring the induced changes in both mobility and Raman
      intensity. If the intervalley scatterers responsible for the D peak are
      monovalent, their concentration is sufficient to account for the limited
      mobilities currently achievable in graphene on a substrate.

PMID- 20795656
TI  - 3-Benzyl-3-azabicyclo[3.1.1]heptan-6-one: a promising building block for
      medicinal chemistry.
AB  - An efficient two-step multigram synthesis of the previously unknown 3-benzyl-3
      azabicyclo[3.1.1]heptan-6-one is described. The compound is shown to be a
      promising building block for further selective derivatization of the cyclobutane
      ring providing novel conformationally restricted piperidine derivatives.

PMID- 20795657
TI  - Plant growth and metal distribution in tissues of Prosopis juliflora-velutina
      grown on chromium contaminated soil in the presence of Glomus deserticola.
AB  - Arbuscular mycorrhizal fungi have been known to increase metal uptake in plants.
      In this study, mesquite (Prosopis juliflora-velutina) inoculated with Glomus
      deserticola or amended with EDTA were grown for 30 days in soil containing
      Cr(III) or Cr(VI) at 0, 40, 80, and 160 mg kg(-1). Total amylase activity (TAA)
      was monitored as a stress indicator. Element concentrations and distribution in
      tissue were determined using ICP-OES, electron scanning microprobe, and TEM.
      Inoculated Cr(VI) treated plants had 21% and 30% more Cr than uninoculated and
      EDTA treated roots, respectively, at 80 mg Cr kg(-1) treatment. In the case of
      Cr(III), EDTA produced the highest Cr accumulation in roots. TAA was higher in
      inoculated plants grown with Cr(III) at 80 and 160 mg kg(-1) and Cr(VI) at 40 and
      160 mg kg(-1). The X-ray mapping showed higher metal concentrations in the
      vascular system of inoculated plants and the TEM micrographs demonstrated the
      presence of G. deserticola in roots.

PMID- 20795658
TI  - Phase behavior of ketoprofen-poly(lactic acid) drug particles formed by rapid
      expansion of supercritical solutions.
AB  - The present contribution investigates whether it is possible to form stable
      amorphous particles of ketoprofen-poly(lactic acid), naproxen-poly(lactic acid),
      and indomethacin-poly(lactic acid). Amorphization and micronization of these
      poorly water-soluble drugs offer a combined way to improve the solubility and
      enhance the dissolution rate. The particles were formed by pulsed rapid expansion
      of supercritical CO(2) solutions and characterized in the aerosol phase with
      rapid-scan infrared spectroscopy and after collection with scanning electron
      microscopy and X-ray diffraction. None of the three drug-poly(lactic acid)
      mixtures showed long-term stability on the order of weeks against the reversion
      from the amorphous to the crystalline state. Ketoprofen was the only drug that
      formed mixed amorphous particles with at least short-term stability. The long
      term products turned out to be submicrometer- to micrometer-sized particles with
      a crystalline drug core and an amorphous poly(lactic acid) shell. Moreover, we
      found that the poly(lactic acid) coating stabilizes the particles against
      agglomeration.

PMID- 20795659
TI  - Topographically uniform but chemically heterogeneous nanostructures by
      nanoimprinting demixed polymer blends.
AB  - Nanoimprint lithography is applied to fabricate topographically uniform patterns
      onto demixed polymer blend films. The high fidelity of pattern replications is
      achieved for 150 nm polystyrene (PS)/polymethylmethacrylate (PMMA) blend films
      with varying compositions. When imprinted at 150  degrees C, the morphology of
      the blend across the patterned structures is similar to that in the as-casted
      films. Significant morphological evolutions occur for patterns imprinted at 180
      and 210  degrees C. For all the patterns, PMMA is found to segregate into the
      residual layer, driven by the preferential wetting of PMMA onto the SiO(x)
      surfaces. The combined domain coarsening and preferential wetting of PMMA leads
      to the formations of unique encapsulated structures within the topographically
      uniform features, ranging from blocks to threads.

PMID- 20795660
TI  - Modification of carbon substrates by aryl and alkynyl iodonium salt reduction.
AB  - Different carbon materials were modified using iodonium ion reduction creating
      radicals, which after reaction with carbon surfaces formed grafted layers of
      molecules. Several molecules (4-bromophenyl, 4-fluorophenyl, 6-chlorohexyne, and
      4-bromobutyne) were grafted on glassy carbon and Vulcan XC72 carbon substrates.
      Carbon substrates were shown to be free of halogen atoms; therefore, the
      quantification of the grafted groups containing halogen atoms was facilitated.
      The grafting of the different molecules was first electrochemically studied on
      glassy carbon electrodes using cyclic voltammetry, in order to determine the
      reduction potential of the corresponding iodonium ions. Voltammetric study using
      Fe(CN)(6)(4-) and Fe(CN)(6)(3-) probe molecules and XPS characterization were
      also used to evidence the effectiveness of grafting from iodonium ion reduction
      reaction. Reduction potentials were found in the range from -0.9 V vs SCE to -1.0
      V vs SCE, lower than those for corresponding diazonium ion reduction reaction on
      glassy carbon (close to -0.3 V vs SCE). Therefore, grafted layers from iodonium
      ions were carried out on carbon Vulcan XC72 powder using NaBH(4) as reducing
      agent. Functionalized carbon powders were characterized by elemental analysis,
      thermogravimetric analysis, and X-ray photoelectron spectroscopy to evidence the
      presence of grafted molecules on the materials. However, low grafting yields were
      obtained. Then, several synthesis parameters were studied to optimize the
      grafting reactions, such as the control of the addition of reactants and their
      concentrations, leading to increase the surface concentration by a factor 2. At
      last, according to XPS measurements the grafting of alkinyliodonium ions led to
      very low surface concentrations (0.5 wt % for 6-chlorohexyne), whereas elemental
      analysis and TGA indicate ca. 2.4 wt % and ca. 5 wt %, respectively.

PMID- 20795661
TI  - Determining the dielectric constant inside pores of nanofiltration membranes from
      membrane potential measurements.
AB  - The membrane potential technique was applied to a nanofiltration polyamide
      membrane to determine its mean pore radius and the dielectric constant of
      electrolyte solutions inside pores. To our knowledge, this is the first attempt
      to assess these features from membrane potential measurements. Membrane potential
      data were analyzed by means of the SEDE (steric electric and dielectric
      exclusion) transport model. Experiments were conducted with single-salt solutions
      of NaCl and CaCl(2) and mixed-salt solutions of NaCl and CaCl(2) at various
      concentrations. It was shown that the pore-size values deduced from the high
      concentration limit of the membrane potential measured with the two single-salt
      solutions are in good agreement. With this parameter being known, the membrane
      potential measured at high salt concentration with electrolyte mixtures was
      further used to compute the dielectric constant inside pores. The latter was
      found to be smaller than its bulk value and to decrease when sodium ions were
      replaced by calcium ions.

PMID- 20795663
TI  - One-step synthesis and assembly of two-dimensional arrays of mercury sulfide
      nanocrystal aggregates at the air/water interface.
AB  - Ordered two-dimensional (2D) arrays of beta-HgS nanocrystal aggregates were
      prepared successfully at the air/water interface through the interfacial reaction
      between Hg(2+) ions in the subphase and H(2)S in the gaseous phase under the
      direction of liquid-expanded monolayers of arachidic acid (AA). These 2D arrays
      are composed of hexagonal or quasi-hexagonal aggregates with the size of several
      hundreds of nanometers that consist of several tens of HgS nanocrystals with the
      size of several nanometers. The formed HgS nanocrystals together with AA
      molecules self-assembled into round aggregates due to the interactions between
      the species, and the aggregates self-assembled into 2D arrays further due to the
      attractions between them. During the self-assembly process, the soft round
      aggregates transformed into hexagonal or quasi-hexagonal ones. The experimental
      conditions, especially the phase states of the AA monolayers and temperature,
      have great influences on the formation of the 2D arrays. To the best of our
      knowledge, this is the first case to get 2D ordered arrays at the air/water
      interface through a one-step synthesis and assembly process.

PMID- 20795662
TI  - Multiwalled carbon nanotube filter: improving viral removal at low pressure.
AB  - The effective removal of viruses by a multiwalled carbon nanotube (MWNT) filter
      is demonstrated over a range of solution chemistries. MS2 bacteriophage viral
      removal by the MWNT filter was between 1.5 and 3 log higher than that observed
      with a recently reported single-walled carbon nanotube (SWNT) filter when
      examined under similar loadings (0.3 mg/cm(2)) of carbon nanotubes (CNTs). The
      greater removal of viruses by the MWNT filter is attributed to a more uniform CNT
      filter matrix that allows effective removal of viruses by physicochemical (depth)
      filtration. Viral removal by the MWNT filter was examined under a broad range of
      water compositions (ionic strength, monovalent and divalent salts, solution pH,
      natural organic matter, alginate, phosphate, and bicarbonate) and filter approach
      velocities (0.0016, 0.0044, and 0.0072 cm/s). Log viral removal increased as the
      fluid approach velocity decreased, exhibiting a dependence on approach velocity
      in agreement with colloid filtration theory for Brownian particles. Viral removal
      improved with increasing ionic strength (NaCl), from 5.06 log removal at 1 mM
      NaCl to greater than 6.56 log removal at 100 mM NaCl. Addition of calcium ions
      also enhanced viral removal, but the presence of magnesium ions resulted in a
      decrease in viral removal. Solution pH also played an important role in viral
      removal, with log removals of 8.13, 5.38, and 4.00 being documented at solution
      pH values of 3.0, 5.5, and 9.0, respectively. Dissolved natural organic matter
      (NOM) had a negligible effect on viral removal at low concentration (1 mg/L), but
      higher concentrations of NOM significantly reduced the viral removal by the MWNT
      filter, likely due to steric repulsion. Addition of alginate (model
      polysaccharide) also caused a marked decrease in viral removal by the MWNT
      filter. This highly scalable MWNT-filter technology at gravity-driven pressures
      presents new, cost-effective options for point-of-use filters for viral removal.

PMID- 20795664
TI  - Influence of taxonomic relatedness and chemical mode of action in acute
      interspecies estimation models for aquatic species.
AB  - Ecological risks to aquatic organisms are typically assessed using acute toxicity
      data for relatively few species and with limited understanding of relative
      species sensitivity. We developed a comprehensive set of interspecies correlation
      estimation (ICE) models based on acute toxicity data for aquatic organisms and
      evaluated three key sources of model uncertainty: taxonomic relatedness, chemical
      mode of action (MOA), and model parameters. Models are least-squares regressions
      of acute toxicity of surrogate and predicted species. A total of 780 models were
      derived from acute values for 77 species of aquatic organisms and over 550
      chemicals. Cross-validation of models showed that accurate model prediction was
      greatest for models with surrogate and predicted taxa within the same family (91%
      of predictions within 5-fold of measured values). Recursive partitioning provided
      user guidance for selection of robust models using model mean square error and
      taxonomic relatedness. Models built with a single MOA were more robust than
      models built using toxicity values with multiple MOAs, and improve predictions
      among species pairs with large taxonomic distance (e.g., within phylum). These
      results indicate that between-species toxicity extrapolation can be improved
      using MOA-based models for less related taxa pairs and for those specific MOAs.

PMID- 20795665
TI  - Swelling and collapse of an adsorbed pH-responsive film-forming microgel measured
      by optical reflectometry and QCM.
AB  - The swelling and deswelling of a pH-responsive electrosterically stabilized
      poly[2-(diethylamino)ethyl methacrylate] microgel adsorbed to silica surfaces
      have been quantified using the techniques of optical reflectometry (OR) and
      quartz crystal microbalance (QCM). It is shown that by utilizing and comparing OR
      measurements performed on wafers with differing oxide layer thicknesses the
      adsorbed amount and film thickness of the adsorbed microgel in both the swollen
      and deswollen forms can be determined. Also, the kinetics of the transition can
      be followed, revealing that collapse is a slower process than swelling, and
      direct support is provided for the formation of a dense outer layer or skin
      during collapse that slows the deswelling process. It is shown that the
      adsorption of this low glass transition temperature film-forming microgel latex
      is robust to changes in pH after an initial swelling event which is responsible
      for desorption of a large and variable fraction of the initially adsorbed
      polymer. Subsequent deswelling and swelling of the adsorbed film indicates that
      adsorption to a surface greatly hinders the volumetric swelling capacity of the
      microgel film. In its swollen state the film is only 3-4 times thicker than the
      collapsed film, whereas for particles in bulk the volume increases by a factor of
      20 upon protonation of the tertiary amine residues. QCM results show that even in
      the collapsed form the film contains a considerable amount of water. Further, the
      viscoelasticity of the deswollen film is similar to that of the swollen film,
      suggesting that the degree of cross-linking is the primary determinant of
      viscoelasticity.

PMID- 20795666
TI  - Broadening the global reach of the United States Environmental Protection Agency
      (USEPA) is vital to combating globalized environmental problems.

PMID- 20795668
TI  - Gold nanofingers for molecule trapping and detection.
AB  - Here we demonstrate a molecular trap structure that can be formed to capture
      analyte molecules in solution for detection and identification. The structure is
      based on gold-coated nanoscale polymer fingers made by nanoimprinting technique.
      The nanofingers are flexible and their tips can be brought together to trap
      molecules, while at the same time the gold-coated fingertips form a reliable
      Raman hot spot for molecule detection and identification based on surface
      enhanced Raman spectroscopy (SERS). The molecule self-limiting gap size control
      between fingertips ensures ultimate SERS enhancement for sensitive molecule
      detection. Furthermore, these type of structures, resulting from top-down meeting
      self-assembly, can be generalized for other applications, such as plasmonics,
      meta-materials, and other nanophotonic systems.

PMID- 20795669
TI  - Dopamine-induced mineralization of calcium carbonate vaterite microspheres.
AB  - Two biogenic materials from mussels are attracting attention from scientists:
      calcium carbonate (CaCO(3)), the most widely studied biomineral that composes the
      shell, or nacre, of mussels, and dopamine, a small catechol-containing biomimetic
      molecule of adhesive foot proteins secreted by mussels. We have incorporated
      these two materials into the biomimetic mineralization process to produce stable
      vaterite microspheres, which are the most unstable crystalline phase of CaCO(3).
      Spherical vaterite crystals were readily formed within two minutes in the
      presence of dopamine undergoing polymerization and were preserved for over two
      months in aqueous solution. The microspheres consisted of nanoparticles smaller
      than 100 nm and exhibited porous and spherulitic cross sections. The prolonged
      maintenance of spherical structure is attributed to the affinitive interaction
      between calcium in the vaterite microspheres and catechols from dopamine
      retarding the dissolution of vaterite and the growth of calcite crystals. The
      mussel-inspired inducement of a stable vaterite phase suggests a facile route for
      the synthesis of complex organic-inorganic hybrid materials utilizing biogenic
      systems.

PMID- 20795670
TI  - Furan hydrogenation over Pt(111) and Pt(100) single-crystal surfaces and Pt
      nanoparticles from 1 to 7 nm: a kinetic and sum frequency generation vibrational
      spectroscopy study.
AB  - Sum frequency generation surface vibrational spectroscopy and kinetic
      measurements using gas chromatography have been used to systematically study the
      adsorption and hydrogenation of furan over Pt(111) and Pt(100) single-crystal
      surfaces and size-controlled 1.0-nm, 3.5-nm and 7.0-nm Pt nanoparticles at Torr
      pressures (10 Torr of furan, 100 Torr of H(2)) to form dihydrofuran,
      tetrahydrofuran, and the ring-cracking products butanol and propylene. As
      determined by SFG, the furan ring lies parallel to all Pt surfaces studied under
      hydrogenation conditions. Upright THF and the oxametallacycle intermediate are
      observed over the nanoparticle catalysts under reaction conditions. Butoxy
      increases in surface concentration over Pt(111) with increasing temperature in
      agreement with selectivity trends.

PMID- 20795671
TI  - Flux of perfluorinated chemicals through wet deposition in Japan, the United
      States, and several other countries.
AB  - The widespread distribution of perfluorinated chemicals (PFCs) in different
      environmental matrices has prompted concern about the sources, fate, and
      transport of these classes of chemicals. PFCs are present in the atmosphere, but
      only a few studies have investigated their occurrence in precipitation. In this
      study, concentrations of 20 PFCs, including C3-C5 short-chain PFCs, were
      quantified using HPLC-MS/MS in precipitation samples from Japan (n = 31), the
      United States (n = 12), China (n = 5), India (n = 2), and France (n = 2). Among
      the PFCs measured, perfluoropropanoic acid (PFPrA) was detected in all of the
      precipitation samples. Average total PFC concentrations ranged from 1.40 to 18.1
      ng/L for the seven cities studied. The greatest total PFC concentrations were
      detected in Tsukuba, Japan, whereas the lowest concentrations were detected in
      Patna, India. PFPrA, perfluorooctanoic acid (PFOA), and perfluorononanoic acid
      (PFNA) were found to be the dominant PFCs in Japanese and U.S. precipitation
      samples. No observable seasonal trend was found in precipitation samples from two
      locations in Japan. Annual fluxes of PFCs were estimated for Japan and the U.S.
      and the evidence for precipitation as an effective scavenger of PFCs in the
      atmosphere is reported.

PMID- 20795672
TI  - Proteomic analysis of proteins selectively associated with hydroxyapatite,
      brushite, and uric acid crystals precipitated from human urine.
AB  - The aim of this study was to compare the intracrystalline protein profiles of
      hydroxyapatite (HA), brushite (BR), and uric acid (UA) crystals precipitated from
      the same urine samples. HA, BR, and UA crystals were precipitated on two
      different occasions from the same pooled healthy urine. Crystals were washed to
      remove surface-bound proteins, and their composition was confirmed using Fourier
      transform infrared spectroscopy (FTIR) and field emission scanning electron
      microscopy (FESEM) coupled with energy dispersive X-ray analysis (EDAX). SDS-PAGE
      was used for visual comparison of the protein content of the demineralised
      crystal extracts, which were analyzed using liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). HA comprised nanosized particles interspersed with
      organic material, which was absent from the BR and UA crystals. The number and
      type of individual proteins differed between the 3 minerals: 45 proteins were
      detected in the HA crystal extracts and 77 in the BR crystals, including a number
      of keratins, which were regarded as methodological contaminants. After excluding
      the keratins, 21 proteins were common to both HA and BR crystals. Seven
      nonkeratin proteins were identified in the UA extracts. Several proteins
      consistently detected in the HA and BR crystal extracts have been previously
      implicated in kidney stone disease, including osteopontin, prothrombin, protein
      S100A9 (calgranulin B), inter-alpha-inhibitor, alpha1-microglobulin bikunin
      (AMBP), heparan sulfate proteoglycan, and Tamm-Horsfall glycoprotein, all of
      which are strong calcium binders. We concluded that the association of proteins
      with HA, BR, and UA crystals formed in healthy urine is selective and that only a
      few of the numerous proteins present in healthy urine are likely to play any
      significant role in preventing stone pathogenesis.

PMID- 20795674
TI  - Phagocytosis of biocompatible gold nanoparticles.
AB  - We report the evidence for the cellular uptake of gold nanoparticles via the
      phagocytosis mechanism in murine macrophage cells strongly supported by TEM and
      optical microscopy. Nanoparticles were prepared using several biocompatible
      molecules of choice (5-aminovaleric acid, l-DOPA, melatonin, and serotonin
      hydrochloride) as stabilizers for gold colloids. Their surface chemistry was
      fully characterized by UV-vis, ATR-FTIR, (1)H NMR, and HR-MAS (1)H NMR
      spectroscopies, and size distribution was determined by CPS disc centrifuge and
      TEM. Differences in coatings were evaluated against cellular uptake, and a
      preferential movement of macrophages toward 5-aminovaleric acid-modified gold
      nanoparticles was shown, leading to the fast accumulation of nanoparticles in the
      cytosol.

PMID- 20795673
TI  - Activation and specificity of human caspase-10.
AB  - Two apical caspases, caspase-8 and -10, are involved in the extrinsic death
      receptor pathway in humans, but it is mainly caspase-8 in its apoptotic and
      nonapoptotic functions that has been an intense research focus. In this study we
      concentrate on caspase-10, its mechanism of activation, and the role of the
      intersubunit cleavage. Our data obtained through in vitro dimerization assays
      strongly suggest that caspase-10 follows the proximity-induced dimerization model
      for apical caspases. Furthermore, we compare the specificity and activity of the
      wild-type protease with a mutant incapable of autoprocessing by using positional
      scanning substrate analysis and cleavage of natural protein substrates. These
      experiments reveal a striking difference between the wild type and the mutant,
      leading us to hypothesize that the single chain enzyme has restricted activity on
      most proteins but high activity on the proapoptotic protein Bid, potentially
      supporting a prodeath role for both cleaved and uncleaved caspase-10.

PMID- 20795675
TI  - An X-ray spectromicroscopy study of protein adsorption to polystyrene
      poly(ethylene oxide) blends.
AB  - Synchrotron-based X-ray photoemission electron microscopy (X-PEEM) and atomic
      force microscopy (AFM) were used to characterize the composition and surface
      morphology of thin films of a polystyrene-poly(ethylene oxide) blend (PS-PEO),
      spun cast from dichloromethane at various mass ratios and polymer concentrations.
      X-PEEM reveals incomplete segregation with ~30% of PS in the PEO region and vice
      versa. Protein (human serum albumin) adsorption studies show that this partial
      phase separation leads to greater protein repellency in the PS region, whereas
      more protein is detected in the PEO region compared to control samples.

PMID- 20795676
TI  - pH sensitive polymer nanoparticles: effect of hydrophobicity on self-assembly.
AB  - The influence of hydrophobicity on formation, stability, and size of pH
      responsive methacryloylated oligopeptide-based polymer nanoparticles has been
      studied by dynamic light scattering (DLS), transmission electron microscopy (Cryo
      TEM), and NMR. Different polyanions/surfactant systems have been studied at
      constant polymer concentration and within a broad range of surfactant
      concentrations. The two newly synthesized pH-sensitive hydrophobic polyanions,
      poly(N(omega)-methacryloyl glycyl-L-leucine) and poly(N(omega)-methacryloyl
      glycyl-L-phenylalanyl-L-leucinyl-glycine), and three nonionic surfactants
      (Brij97, Brij98, and Brij700) have been investigated. The surfactants were
      different in the length of hydrophilic poly(ethylene oxide) (PEO) chain. In
      surfactant-free solution at basic pH, the polyanions form hydrophobic domains. In
      the presence of a surfactant, our results prove the complex formation at high pH
      between the nonionic surfactant and the polyelectrolyte; a pearl-necklace
      structure is formed. At low pH below critical pH (pH(tr)), reversible nanoscale
      structures occur in solutions for all systems. The detailed mechanism of the
      formation of pH-sensitive nanoparticles from polymer-surfactant complex with
      varying pH is established. Our results suggest that the polymer hydrophobicity is
      of primary importance in pretransitional behavior of the complex. Once
      preliminary nanoparticle nuclei are formed, the hydrophobicity of the polymer
      plays a minor role on further behavior of formed nanostructures. The subsequent
      transformation of nanoparticles is determined by the surfactant hydrophilicity,
      the length of hydrophilic tail that prevents further aggregation due to steric
      repulsions.

PMID- 20795677
TI  - GARLig: a fully automated tool for subset selection of large fragment spaces via
      a self-adaptive genetic algorithm.
AB  - In combinatorial chemistry, molecules are assembled according to combinatorial
      principles by linking suitable reagents or decorating a given scaffold with
      appropriate substituents from a large chemical space of starting materials. Often
      the number of possible combinations greatly exceeds the number feasible to handle
      by an in-depth in silico approach or even more if it should be experimentally
      synthesized. Therefore, powerful tools to efficiently enumerate large chemical
      spaces are required. They can be provided by genetic algorithms, which mimic
      Darwinian evolution. GARLig (genetic algorithm using reagents to compose ligands)
      has been developed to perform subset selection in large chemical compound spaces
      subject to target-specific 3D-scoring criteria. GARLig uses different scoring
      schemes, such as AutoDock4 Score, GOLDScore, and DrugScore(CSD), as fitness
      functions. Its genetic parameters have been optimized to characterize
      combinatorial libraries with respect to the binding to various targets of
      pharmaceutical interest. A large tripeptide library of 20(3) members has been
      used to profile amino acid frequencies in putative substrates for trypsin,
      thrombin, factor Xa, and plasmin. A peptidomimetic scaffold assembled from a
      selection of a 25(3) building block was used to test the performance of the
      evolutionary algorithm in suggesting potent inhibitors of the enzyme cathepsin D.
      In a final case study, our program was used to characterize and rank a
      combinatorial drug-like library comprising 33,750 potential thrombin inhibitors.
      These case studies demonstrate that GARLig finds experimentally confirmed potent
      leads by processing a significantly smaller subset of the fully enumerated
      combinatorial library. Furthermore, the profiles of amino acids computed by the
      genetic algorithm match the observed amino acid frequencies found by screening
      peptide libraries in substrate cleavage assays.

PMID- 20795678
TI  - STPR, a 23-amino acid tandem repeat domain, found in the human function-unknown
      protein ZNF821.
AB  - The STPR motif is composed of 23-amino acid repeats aligned contiguously. STPR
      was originally reported as the DNA-binding domain of the silkworm protein FMBP-1.
      ZNF821, the human protein that contains the STPR domain, is a zinc finger protein
      of unknown function. In this study, we prepared peptides of silkworm FMBP-1 STPR
      (sSTPR) and human ZNF821 STPR (hSTPR) and compared their DNA binding behaviors.
      This revealed that hSTPR, like sSTPR, is a double-stranded DNA-binding domain.
      Sequence-independent DNA binding affinities and alpha-helix-rich DNA-bound
      structures were comparable between the two STPRs, although the specific DNA
      sequence of hSTPR is still unclear. In addition, a subcellular expression
      experiment showed that the hSTPR domain is responsible for the nuclear
      localization of ZNF821. ZNF821 showed a much slower diffusion rate in the
      nucleus, suggesting the possibility of interaction with chromosomal DNA. STPR
      sequences are found in many proteins from vertebrates, insects, and nematodes.
      Some of the consensus amino acid residues would be responsible for DNA binding
      and concomitant increases in alpha-helix structure content.

PMID- 20795679
TI  - Unusual adsorption behavior on metal-organic frameworks.
AB  - Metal-organic frameworks (MOFs) have shown adsorption behavior that is not
      observed in other microporous materials such as zeolites or activated carbons.
      This study used grand canonical Monte Carlo simulation to evaluate a particular
      form of behavior, which corresponds to the presence of unusual type V adsorption
      isotherms. Study of a series of MOFs in the IRMOF family, containing chemically
      similar linkers of different length, showed that the presence of type V
      adsorption depends on a fine balance between the strength of the fluid-fluid and
      fluid-solid interactions, which in turn is a strong function of the length of the
      linker and therefore the pore size. A transition from type V behavior to the more
      common type I behavior is observed as the temperature increases. The temperature
      at which this transition occurs increases, and the transition becomes more
      diffuse, as the length of the linker increases. This type V behavior leads to an
      interesting possibility in the design of MOF adsorbents for use in gas separation
      and gas storage applications.

PMID- 20795680
TI  - Potent mutagenicity of 3-methylindole requires pulmonary cytochrome P450-mediated
      bioactivation: a comparison to the prototype cigarette smoke mutagens B(a)P and
      NNK.
AB  - 3-Methylindole (3MI) is a preferential pneumotoxicant found in cigarette smoke. A
      number of lung-expressed human cytochrome P450 enzymes, including 1A1, 2F1, and
      2A13, catalyze the metabolism of 3MI to reactive intermediates that fragment DNA,
      measured with the Comet assay to assess DNA damage, in a cytochrome P450
      dependent manner in primary normal human lung cells in culture, but the
      mutagenesis of 3MI has been controversial. In the present study, the mutagenic
      potential of 3MI was compared to the prototypical cigarette smoke carcinogens
      benzo(a)pyrene (B(a)P) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).
      3MI, B(a)P, and NNK were incubated with the Salmonella typhimurium strain TA98,
      which is known to detect the most common subtype of cigarette smoke-induced
      mutagenicity, frameshift mutations in DNA, and with Salmonella typhimurium strain
      TA100, which detects base pair substitution mutants, with five sources of P450
      mediated bioactivation: rat liver S9, human lung microsomes, recombinant CYP2A13,
      purified CYP2F3, and recombinant CYP1A1. Only B(a)P was mutagenic in TA100, and
      it was bioactivated by human lung microsomes and rat liver S9 sources of P450s.
      However, with the TA98 strain, CYP1A1, CYP2A13, CYP2F3, and human lung microsomes
      bioactivated 3MI to highly mutagenic intermediates, whereas neither human nor rat
      liver S9 subcellular fractions formed mutagenic intermediates from 3MI.
      Quantitative Western blot analysis verified that all three respiratory enzymes
      were present in human lung microsomes in widely varying amounts. These results
      indicate that metabolism of 3MI by human lung-expressed cytochrome P450 enzymes
      but not hepatic P450s elicits equivalent or higher mutagenicity than the
      prototype cigarette smoke mutagens B(a)P and NNK and indicates that 3MI is a
      likely human pulmonary carcinogen.

PMID- 20795682
TI  - New laboratory intercomparison of the ozone absorption coefficients in the mid
      infrared (10 MUm) and ultraviolet (300-350 nm) spectral regions.
AB  - Knowing the ozone absorption cross sections in the ultraviolet and infrared
      spectral range, with an accuracy of better than 1%, is of the utmost importance
      for atmospheric remote-sensing applications. For this reason, various ozone
      intensity intercomparisons and measurements have been published these last years.
      However, the corresponding results proved not to be consistent and thus have
      raised a controversial discussion in the community of atmospheric remote-sensing.
      This study, where great care has been taken to avoid any possible error, reports
      a new laboratory intercomparison of the ozone absorption coefficients in the mid
      infrared (10 MUm) and ultraviolet (300-350 nm) spectral regions. It gives a new
      piece of information to the puzzling problem concerning the ozone IR and UV cross
      sections and confirms that the IR and UV cross sections recommended in the
      literature are in disagreement of about 4%.

PMID- 20795681
TI  - Effect of a microemulsion system on hapten-peptide reactivity studies: examples
      of hydroxycitronellal and citral, fragrance skin sensitizers, with glutathione.
AB  - In chemico methods, based on the assessment of hapten reactivity toward peptides,
      have been proposed as alternative methods for the assessment of the skin
      sensitizing potential of chemicals. However, even if these approaches seem very
      promising, a major drawback inherent to most in vitro methods is the poor water
      solubility of many organic molecules in aqueous media. Thus, semiorganic media
      based on buffer solutions and organic cosolvents such as ethanol or acetonitrile
      have been proposed, but a narrow equilibrium should be found between the peptide
      and chemical solubilities. Microemulsions have been shown to be very valuable
      when reacting a lipophilic organic compound soluble in hydrophobic media with a
      very hydrophilic organic substance insoluble in most organic solvents. However,
      the reaction rate between polar and apolar reactants can be influenced, in some
      cases, by the use of microemulsions. On the basis of NMR experiments, we have
      compared the reactivity of hydroxycitronellal 1 and citral 2, two weak fragrance
      sensitizers of major clinical relevance, toward glutathione used as a model
      nucleophile in a water/acetonitrile 2:1 mixture and in a microemulsion based on
      chloroform/water/tert-butanol/sodium dodecylsulphate. Hydroxycitronellal and
      citral were found to react with the thiol group of glutathione to form, in both
      media, identical adducts, but the observed reaction rates were found to be
      different. In the case of hydroxycitronellal, the observed reaction rate of
      glutathione addition on the aldehyde was found to be about three times higher in
      the microemulsion compared to the classical semiorganic mixture. In the case of
      citral, the situation was more complex as the Michael addition of glutathione on
      the conjugated double bond was found to be significantly faster in the classical
      semiorganic mixture, while the subsequent reaction of a second glutathione
      molecule on the aldehyde was found to be faster in the microemulsion. This
      chloroform/water/tert-butanol/sodium dodecylsulphate microemulsion, apparently of
      the bicontinuous type according to DOSY data, could be of potential interest for
      the in chemico evaluation of lipophilic chemicals toward peptides to solve
      solubility problems even if the impact on the chemical rate needs to be further
      investigated.

PMID- 20795683
TI  - Terminal alkynes as an ink or background SAM in replacement lithography:
      adventitious versus directed replacement.
AB  - Self-assembled monolayers (SAMs) comprised from n-alkanethiols and terminal
      alkynes were subjected to solutions containing ferrocene-terminated thiol,
      thioacetate, and terminal alkyne. The rate and extent of chemical exchange were
      monitored by scanning tunneling microscopy (STM). In several cases, a rate
      constant for exchange could be obtained by fitting to a model for exchange. In
      each case where this could be accomplished, a different rate model gave the best
      fit to the data, suggesting that the mechanism of exchange depended on either or
      both the original SAM and the incoming molecule. In scenarios where the rate of
      exchange was slow, directed exchange was accomplished via STM tip-induced
      lithographic patterning (replacement lithography). The extent of exchange was
      independent of the incoming molecule, suggesting that tip-induced desorption was
      the limiting factor in this process.

PMID- 20795684
TI  - Evaluating the effects of the nonplanarity of nucleic acid bases on NMR, IR, and
      vibrational circular dichroism spectra: a density functional theory computational
      study.
AB  - The pyramidalizations of N9/1 glycosidic nitrogens in DNA and RNA nucleosides,
      recently discovered and analyzed in their ultrahigh-resolution X-ray crystal
      structures ( Sychrovsky ; et al. Nucleic Acid Res. 2009 , 37 , 7321. ), were
      found to have significant effects on the structural interpretation of the
      (3)J(C4/2-H1') and (3)J(C8/6-H1') NMR scalar couplings in purine/pyrimidine
      nucleosides. The calculated effects on IR and vibrational circular dichroism
      (VCD) spectra were only minor. The calculated structural deformations in
      nucleosides, depending on sugar-to-base orientation, gave rise to corrections in
      the phase shift of the Karplus equations for the (3)J(C8/6-H1') and (3)J(C4/2
      H1') couplings ranging from -26 degrees  to +25 degrees  and from -5.7 degrees 
      to +2.0 degrees , respectively. The sign alternation of this correction in syn
      and anti nucleosides arises from the stereoinversion of the N9/1 glycosidic
      nitrogen occurring upon reorientation of the glycosidic torsion. The effect was
      calculated consistently in the dG, dA, dC, dT, rA, and rG nucleosides.
      Utilization of the calculated phase-shift corrections in the design of Karplus
      equations for the (3)J couplings was suggested, and the effects on structural
      interpretation of the experimental couplings were evaluated.

PMID- 20795685
TI  - Adhesion through single peptide aptamers.
AB  - Aptamer and antibody mediated adhesion is central to biological function and is
      valuable in the engineering of "lab on a chip" devices. Single molecule force
      spectroscopy using optical tweezers enables direct nonequilibrium measurement of
      these noncovalent interactions for three peptide aptamers selected for glass,
      polystyrene, and carbon nanotubes. A comprehensive examination of the strong
      attachment between antifluorescein 4-4-20 and fluorescein was also carried out
      using the same assay. Bond lifetime, barrier width, and free energy of activation
      are extracted from unbinding histogram data using three single molecule pulling
      models. The evaluated aptamers appear to adhere stronger than the fluorescein
      antibody under no- and low-load conditions, yet weaker than antibodies at loads
      above ~25 pN. Comparison to force spectroscopy data of other biological linkages
      shows the diversity of load dependent binding and provides insight into linkages
      used in biological processes and those designed for engineered systems.

PMID- 20795686
TI  - Tautomerism in cytosine and uracil: a theoretical and experimental X-ray
      absorption and resonant auger study.
AB  - The core level photoabsorption spectra of the nucleobases cytosine and uracil in
      the gas phase have been measured and the results interpreted with theoretical
      calculations using an ab initio Green's function approach. A single tautomer of
      uracil is populated, in agreement with previous work, while three tautomers of
      cytosine are clearly identified, whose identity and relative populations at the
      temperature of the experiment were reported previously. The second-order ADC
      approach to polarization propagator was employed in calculations of X-ray
      photoabsorption energies and intensities. The theoretical spectra have been
      constructed as Boltzmann-factor-weighted sums of individual tautomer spectra.
      These theoretical spectra are in good agreement with the experimental
      photoabsorption results at the oxygen, nitrogen, and carbon edges. In addition we
      report resonant Auger spectra of the valence band of cytosine, which support
      previous assignments of the character of the valence band states.

PMID- 20795688
TI  - A novel and universal route to SiO2-supported organic/inorganic hybrid noble
      metal nanomaterials via surface RAFT polymerization.
AB  - Polymer-encapsulated gold or silver nanoparticles were synthesized and sterically
      stabilized by a shell layer of poly(4-vinylpyridine) (P4VP) grafted on SiO(2)
      nanoparticles that acts as a scaffold for the synthesis of hybrid noble metal
      nanomaterials. The grafting P4VP shell was synthesized via surface reversible
      addition-fragmentation chain transfer (RAFT) polymerization of 4-vinylpyridine
      (4VP) using SiO(2)-supported benzyl 9H-carbazole-9-carbodithioate (SiO(2)-BCBD)
      as the RAFT agent. The covalently tethered P4VP shell can coordinate with various
      transition metal ions such as Au(3+) or Ag(+) and therefore stabilize the
      corresponding Au or Ag nanoparticles reduced in situ by sodium borohydride
      (NaBH(4)) or trisodium citrate. The SiO(2)-supported RAFT agent and the Au or Ag
      nanoparticles embedded in the P4VP shell layer were characterized by UV-vis
      spectrophotometer, X-ray diffraction (XRD), transmission electron microscopy
      (TEM), X-ray photoelectron spectroscopy (XPS), and surface-enhanced Raman
      spectroscopy (SERS).

PMID- 20795689
TI  - Photoionization dynamics of ammonia (B(1)E''): dependence on ionizing photon
      energy and initial vibrational level.
AB  - In this article we present photoelectron spectra and angular distributions in
      which ion rotational states are resolved. This data enables the comparison of
      direct and threshold photoionization techniques. We also present angle-resolved
      photoelectron signals at different total energies, providing a method to scan the
      structure of the continuum in the near-threshold region. Finally, we have studied
      the influence of vibrational excitation on the photoionization dynamics.

PMID- 20795687
TI  - Escherichia coli mutants that synthesize dephosphorylated lipid A molecules.
AB  - The lipid A moiety of Escherichia coli lipopolysaccharide is a hexaacylated
      disaccharide of glucosamine that is phosphorylated at the 1 and 4' positions.
      Expression of the Francisella novicida lipid A 1-phosphatase FnLpxE in E. coli
      results in dephosphorylation of the lipid A proximal unit. Coexpression of FnLpxE
      and the Rhizobium leguminosarum lipid A oxidase RlLpxQ in E. coli converts much
      of the proximal glucosamine to 2-amino-2-deoxygluconate. Expression of the F.
      novicida lipid A 4'-phosphatase FnLpxF in wild-type E. coli has no effect because
      FnLpxF cannot dephosphorylate hexaacylated lipid A. However, expression of FnLpxF
      in E. coli lpxM mutants, which synthesize pentaacylated lipid A lacking the
      secondary 3'-myristate chain, causes extensive 4'-dephosphorylation. Coexpression
      of FnLpxE and FnLpxF in lpxM mutants results in massive accumulation of lipid A
      species lacking both phosphate groups, and introduction of RlLpxQ generates
      phosphate-free lipid A variants containing 2-amino-2-deoxygluconate. The proposed
      lipid A structures were confirmed by electrospray ionization mass spectrometry.
      Strains with 4'-dephosphorylated lipid A display increased polymyxin resistance.
      Heptose-deficient mutants of E. coli lacking both the 1- and 4'-phosphate
      moieties are viable on plates but sensitive to CaCl(2). Our methods for
      reengineering lipid A structure may be useful for generating novel vaccines and
      adjuvants.

PMID- 20795690
TI  - HiRE-RNA: a high resolution coarse-grained energy model for RNA.
AB  - Although RNAs play many cellular functions, the gap between their sequences and
      3D structures is increasing and our knowledge of RNA thermodynamics and long time
      scale dynamics is still limited at an atomic level of detail. In principle, all
      atom molecular dynamics (MD) and replica exchange molecular dynamics (REMD)
      simulations can investigate these issues, but with current computer facilities,
      these simulations in explicit solvent have been limited to small RNAs and to
      short times. To move to larger systems, we can resort to coarse-graining. In this
      study, we present HiRE-RNA, a generic high resolution coarse-grained model for
      RNA, and report MD and REMD simulations on two RNAs of 22 and 36 nucleotides.
      Starting from unfolded structures, the 22-mer folds within 1.8 A rmsd from the
      NMR structure, while the 36-mer folds within 4.6 A rmsd. Current results suggest
      that further optimization of the HiRE-RNA force field should open the door to a
      relevant model for studying large RNAs, such as riboswitches, and for predicting
      3D structures from secondary structure information.

PMID- 20795691
TI  - Interaction of ethanol and water with the {1014} surface of calcite.
AB  - Molecular dynamics simulations have been used to model the interaction between
      ethanol, water, and the {1014} surface of calcite. Our results demonstrate that a
      single ethanol molecule is able to form two interactions with the mineral surface
      (both Ca-O and O-H), resulting in a highly ordered, stable adsorption layer. In
      contrast, a single water molecule can only form one or other of these
      interactions and is thus less well bound, resulting in a more unstable adsorption
      layer. Consequently, when competitive adsorption is considered, ethanol dominates
      the adsorption layer that forms even when the starting configuration consists of
      a complete monolayer of water at the surface. The computational results are in
      good agreement with the results from atomic force microscopy experiments where it
      is observed that a layer of ethanol remains attached to the calcite surface,
      decreasing its ability to interact with water and for growth at the {1014}
      surface to occur. This observation, and its corresponding molecular explanation,
      may give some insight into the ability to control crystal form using mixtures of
      different organic solvents.

PMID- 20795692
TI  - Isotopic analysis of dissolved organic nitrogen in soils.
AB  - Determination of the isotopic signature of dissolved organic nitrogen (DON) is
      important to assess its dynamics in terrestrial ecosystems. Analysis of (15)N
      DON, however, has been hindered by the lack of simple, reliable, and established
      methods. We evaluate three off-line techniques for measuring the (15)N signature
      of DON in the presence of inorganic N using a persulfate digestion followed by
      microdiffusion. The (15)N-DON signature is calculated from the difference between
      total dissolved (15)N ((15)N-TDN) and inorganic (15)N. We quantified the (15)N
      recovery and signature of DON, NH(4)(+), and NO(3)(-) in a series of inorganic
      N/DON mixtures (with a TDN concentration of 10 mg N L(-1)) for three lab
      protocols. Phenylalanine was used as a model compound for DON. The best lab
      protocol determined the concentration of inorganic N and TDN prior to diffusion
      using improved spectrophotometric techniques. An accuracy of 88% for (15)N-DON
      should be routinely possible; coefficient of variation was <2.9%. Hence, reliable
      (15)N-DON values are obtained over an DON concentration range of 2.3-10 mg L(-1).
      High levels of DON could influence the accuracy of (15)N-NO(3)(-) mainly at
      DON:NO(3)(-) ratios above 0.4. Evaluation of alternative NO(3)(-) measurements is
      still necessary. Our method is applicable for soil solution samples and soil
      extracts and has no risk of cross-contamination. Potential applications are
      large, in particular for (15)N tracer studies, and will increase our insight in
      DON behavior in soils.

PMID- 20795693
TI  - Ion transfer voltammetry by a simple two polarized interfaces setup.
AB  - Cyclic voltammetry and square wave voltammetry have been used to investigate the
      transfer of highly hydrophilic ions, including anions and cations, by a simple
      two polarized interfaces setup. The expression of apparent half-wave potential
      has been established detailedly by virtue of theory of sampled-current
      voltammetry involving semi-infinite linear diffusion, which indicates that the
      property of coupled ion transfer reaction has an effect on the position of the
      voltammogram on the potential scale. Since the data obtained agree well with
      literature values, it seems convincing to determine the transfer energies of
      those highly hydrophilic ions which are very important and have not been reported
      yet. Then it has been demonstrated as a novel way in combination with sensitive
      and fast square wave voltammetry for determining the transfer Gibbs energy of
      complex ions such as miscellaneous inorganic ions.

PMID- 20795694
TI  - Atomic charges derived from electrostatic potentials for molecular and periodic
      systems.
AB  - We present a method for fitting atomic charges to the electrostatic potential
      (ESP) of periodic and nonperiodic systems. This method is similar to the method
      of Campa et al. [ J. Chem. Theory Comput. 2009, 5, 2866]. We compare the Wolf and
      Ewald long-range electrostatic summation methods in calculating the ESP for
      periodic systems. We find that the Wolf summation is computationally more
      efficient than the Ewald summation by about a factor of 5 with comparable
      accuracy. Our analysis shows that the choice of grid mesh size influences the
      fitted atomic charges, especially for systems with buried (highly coordinated)
      atoms. We find that a maximum grid spacing of 0.2-0.3 A is required to obtain
      reliable atomic charges. The effect of the exclusion radius for point selection
      is assessed; we find that the common choice of using the van der Waals (vdW)
      radius as the exclusion radius for each atom may result in large deviations
      between the ESP generated from the ab initio calculations and that computed from
      the fitted charges, especially for points closest to the exclusion radii. We find
      that a larger value of exclusion radius than commonly used, 1.3 times the vdW
      radius, provides more reliable results. We find that a penalty function approach
      for fitting charges for buried atoms, with the target charge taken from Bader
      charge analysis, gives physically reasonable results.

PMID- 20795695
TI  - Simulation of two-dimensional ultraviolet spectroscopy of amyloid fibrils.
AB  - Revealing the structure and aggregation mechanism of amyloid fibrils is essential
      for the treatment of over 20 diseases related to protein misfolding. Coherent two
      dimensional (2D) infrared spectroscopy is a novel tool that provides a wealth of
      new insight into the structure and dynamics of biomolecular systems. Recently
      developed ultrafast laser sources are extending multidimensional spectroscopy
      into the ultraviolet (UV) region, and this opens up new opportunities for probing
      fibrils. In a simulation study, we show that 2DUV spectra of the backbone of a 32
      residue beta-amyloid (Abeta(9-40)) fibril associated with Alzheimer's disease and
      two intermediate prefibrillar structures carry characteristic signatures of
      fibril size and geometry that could be used to monitor its formation kinetics.
      The dependence of these signals on the fibril size and geometry is explored. We
      demonstrate that the dominant features of the beta-amyloid fibril spectra are
      determined by intramolecular interactions within a single Abeta(9-40), and
      intermolecular interactions at the "external interface" have clear signatures in
      the fine details of these signals.

PMID- 20795696
TI  - Photochemistry of DNA fragments via semiclassical nonadiabatic dynamics.
AB  - Forming upon absorption of a UV photon, excited states of DNA are subject to
      nonadiabatic evolution, via either internal conversion (IC) back to the ground
      state or mutagenesis. Nonadiabatic processes following the formation of the first
      singlet excited states, S1, in 10 different small DNA fragments--4 single 4'H
      nucleosides, 2 Watson-Crick base pairs, and 4 nucleotide quartets--have been
      investigated. Simulations were done via the nonadiabatic direct trajectory
      surface hopping semiclassical dynamics. The electronic wave function was obtained
      with configuration interaction, based on the semiempirical AM1 and PM3
      Hamiltonians with fractional orbital occupation numbers. The evolution of the
      electronic wave function was governed by the time-dependent Schrodinger equation
      with a locally diabatic representation, intrinsically stable near surface
      crossings. The nuclei evolved on adiabatic potential energy surfaces, as
      prescribed by classical Newtonian dynamics, with sudden hops between potential
      energy surfaces to account for nonadiabatic transitions. The "fewest switches"
      surface hopping algorithm coupled the quantum and classical parts of the system.
      The dynamics simulations revealed several routes of nonadiabatic relaxation in
      these systems, which were not reported previously, and also recovered known
      routes of IC.

PMID- 20795697
TI  - Two metals are better than one: investigations on the interactions between
      dinuclear metal complexes and quadruplex DNA.
AB  - Twelve mono- and dimetallic complexes (the metals being Cu(II), Pt(II), and
      Zn(II)) with terpyridine-based ligands have been prepared and fully
      characterized. The X-ray crystal structures of two of the complexes (monometallic
      Cu(II) and Zn(II) complexes with a morpholino-substituted terpyridine ligand) are
      reported. The affinities of the 12 complexes toward duplex and quadruplex (HTelo
      and c-myc) DNA have been investigated using a combination of techniques including
      fluorescent indicator displacement (FID) assay, UV-vis spectroscopy and circular
      dichroism (CD). These studies revealed that the dicopper and diplatinum complexes
      11 and 12 bind very strongly to quadruplex DNA (up to K = 7.97 * 10(6) M(-1)) and
      with good selectivity (up to 100-fold) over duplex DNA. In these dimetallic
      complexes, one of the metals is coordinated to a terpyridine moiety yielding
      square based pyramidal (with Cu(II)) or square planar (with Pt(II)) geometries.
      The second metal is coordinated to a dipicolyl amine linked to terpyridine by a
      three-atom spacer. We propose that these complexes bind to quadruplex DNA via a
      combination of interactions: pi-pi end-stacking between the metal-terpyridine
      fragment and the guanine quartet, and electrostatic/metal-phosphate interactions
      (between the metal-dipicolyl amine fragment and DNA's backbone).

PMID- 20795698
TI  - Polysaccharide-based polyelectrolyte multilayer surface coatings can enhance
      mesenchymal stem cell response to adsorbed growth factors.
AB  - It is generally accepted that both surface chemistry and biochemical cues affect
      mesenchymal stem cell (MSC) proliferation and differentiation. Several growth
      factors that have strong influences on MSC behavior bind to glycosaminoglycans in
      interactions that affect their stability and their biochemical activity. The goal
      of this work was to develop polysaccharide-based polyelectrolyte multilayers
      (PEMs) to bind and stabilize growth factors for delivery to MSCs. Using the
      naturally derived polysaccharides chitosan and heparin, PEMs were constructed on
      gold-coated glass chips, tissue-culture polystyrene (TCPS), and titanium. PEM
      construction and basic fibroblast growth factor (FGF-2) adsorption to PEMs were
      evaluated by Fourier transform surface plasmon resonance, X-ray photoelectron
      spectroscopy, and polarization modulation infrared reflection absorption
      spectroscopy. The functional response of bone marrow-derived ovine MSCs to FGF-2
      on PEM-coated TCPS and titanium was evaluated in vitro, in the presence and
      absence of adsorbed fibronectin. The effect of FGF-2 dose and presentation on MSC
      attachment and proliferation was evaluated using low-serum media, over four days.
      On PEM-coated TCPS, we found that FGF-2 adsorbed to heparin-terminated PEMs with
      adsorbed fibronectin induces greater cell density and a higher proliferation rate
      of MSCs than any of the other conditions tested, including delivery of the FGF-2
      in solution, at an optimally mitogenic dose. Cell densities on day four were 1.8
      times higher when FGF-2 was delivered by adsorption to the PEM than when FGF-2
      was delivered in solution. This system represents a promising candidate for the
      development of surface coatings that can stabilize and potentiate the activity of
      growth factors for therapeutic applications. Interestingly, the same effects were
      not observed when FGF-2 was delivered by adsorption to PEMs on titanium. When the
      polysaccharide-based PEMs were formed on titanium, the proliferative response of
      ovine MSCs to adsorbed FGF-2 was not as strong as the response to FGF-2 delivered
      in solution.

PMID- 20795699
TI  - Evasion of the accelerated blood clearance phenomenon by coating of nanoparticles
      with various hydrophilic polymers.
AB  - The accelerated blood clearance (ABC) phenomenon is induced upon repeated
      injections of poly(ethylene glycol) (PEG)-coated colloidal carriers. It is
      essential to suppress this phenomenon in a clinical setting because the
      pharmacokinetics must be reproducible. In this study, we evaluated the induction
      of the ABC phenomenon using nanoparticles coated with various hydrophilic
      polymers instead of PEG. Nanoparticles encapsulating prostaglandin E1 were
      prepared by the solvent diffusion method from a blend of poly(lactic acid) (PLA)
      and block copolymers consisting of various hydrophilic polymers and PLA. Coating
      of nanoparticles with poly(N-vinyl-2-pyrrolidone) (PVP), poly(4
      acryloylmorpholine), or poly(N,N-dimethylacrylamide) led to extended residence of
      the nanoparticles in blood circulation in rats, although they had a shorter half
      life than the PEG-coated nanoparticles. The ABC phenomenon was not induced upon
      repeated injection of PVP-coated nanoparticles at various time intervals,
      dosages, or frequencies, whereas it was elicited by PEG-coated nanoparticles. In
      addition, anti-PVP IgM antibody, which is estimated to be one of the crucial
      factors for induction of the ABC phenomenon, was not produced after injection of
      PVP-coated nanoparticles. These results suggest that the use of PVP, instead of
      PEG, as a coating material for colloidal carriers can evade the ABC phenomenon.

PMID- 20795700
TI  - New efficient ruthenium sensitizers with unsymmetrical indeno[1,2-b]thiophene or
      a fused dithiophene ligand for dye-sensitized solar cells.
AB  - Two novel ruthenium sensitizers containing unsymmetrical indeno[1,2-b]thiophene
      or a fused dithiophene unit in the ancillary ligand have been designed and
      synthesized. The photovoltaic performance of JK-188 using an electrolyte
      consisting of 0.6 M 1,2-dimethyl-3-propylimidazolium iodide, 0.05 M I(2), 0.1 M
      LiI, 0.05 M guanidinium thiocyanate, and 0.5 M tert-butylpyridine in acetonitrile
      revealed a short-circuit photocurrent density of 18.60 mA/cm(2), an open-circuit
      voltage of 0.72 V, and a fill factor of 0.71, yielding an overall conversion
      efficiency of 9.54%. The cell exhibits a remarkable stability under 1000 h of
      light soaking at 60  degrees C using a quasi-solid-state electrolyte consisting
      of 5 wt % poly(vinylidenefluoride-co-hexafluoropropylene), 0.6 M 1-propyl-2,3
      dimethylimidazolium iodide, 0.5 M N-methylbenzimidazole, and 0.1 M I(2) in 3
      methoxypropionitrile, retaining 97% of the initial efficiency (7.38%).

PMID- 20795701
TI  - Bioactive polyelectrolyte multilayers: hyaluronic acid mediated B lymphocyte
      adhesion.
AB  - A strategy was developed to produce thin, biopolymer-based polyelectrolyte
      multilayer films, based on hyaluronic acid and chitosan, that are able to
      effectively bind B lymphocytes. These films explore CD44-hyaluronate interactions
      and provide a method to make surface-bound B cell arrays without the need for
      nonselective covalent chemistry. The rational design of these films using
      solution deposition variables, such as ionic strength and pH, allows one to
      maximize and fine tune this binding efficiency ex vivo. This work suggests two
      important conditions for successfully attaching B cells to hyaluronate-containing
      polyelectrolyte multilayer films: (1) hyaluronic acid is required for the
      proposed CD44-mediated binding mechanism, and (2) hyaluronic acid deposition
      conditions that favor loops and tails, such as low pH and with added salt, result
      in more available CD44 binding ligands and higher cell binding efficiency.
      Chitosan-terminated films prepared without NaCl in the deposition solutions and
      hyaluronic acid-terminated films prepared with salt, both under pH 3.0 assembly
      conditions, presented a similar high lymphocyte binding efficiency. In the former
      case, however, the binding strength was weaker due to a significant electrostatic
      contribution to the binding. Bioactive polyelectrolyte multilayers for selective
      binding of lymphocytes hold great promise in fields ranging from cell-based
      biosensors to immune system engineering.

PMID- 20795702
TI  - Molecular graph augmentation with rings and functional groups.
AB  - Molecular graphs are a compact representation of molecules but may be too concise
      to obtain optimal generalization performance from graph-based machine learning
      algorithms. Over centuries, chemists have learned what are the important
      functional groups in molecules. This knowledge is normally not manifest in
      molecular graphs. In this paper, we introduce a simple method to incorporate this
      type of background knowledge: we insert additional vertices with corresponding
      edges for each functional group and ring structure identified in the molecule. We
      present experimental evidence that, on a wide range of ligand-based tasks and
      data sets, the proposed augmentation method improves the predictive performance
      over several graph kernel-based quantitative structure-activity relationship
      models. When the augmentation technique is used with the recent pairwise maximal
      common subgraphs kernel, we achieve a significant improvement over the current
      state-of-the-art on the NCI-60 cancer data set in 28 out of 60 cell lines, with
      the other 32 cell lines showing no significant difference in accuracy. Finally,
      on the Bursi mutagenicity data set, we obtain near-optimal predictions.

PMID- 20795703
TI  - Microfluidic cardiac cell culture model (MUCCCM).
AB  - Physiological heart development and cardiac function rely on the response of
      cardiac cells to mechanical stress during hemodynamic loading and unloading.
      These stresses, especially if sustained, can induce changes in cell structure,
      contractile function, and gene expression. Current cell culture techniques
      commonly fail to adequately replicate physical loading observed in the native
      heart. Therefore, there is a need for physiologically relevant in vitro models
      that recreate mechanical loading conditions seen in both normal and pathological
      conditions. To fulfill this need, we have developed a microfluidic cardiac cell
      culture model (MUCCCM) that for the first time allows in vitro hemodynamic
      stimulation of cardiomyocytes by directly coupling cell structure and function
      with fluid induced loading. Cells are cultured in a small (1 cm diameter) cell
      culture chamber on a thin flexible silicone membrane. Integrating the cell
      culture chamber with a pump, collapsible pulsatile valve and an adjustable
      resistance element (hemostatic valve) in series allow replication of various
      loading conditions experienced in the heart. This paper details the design,
      modeling, fabrication and characterization of fluid flow, pressure and stretch
      generated at various frequencies to mimic hemodynamic conditions associated with
      the normal and failing heart. Proof-of-concept studies demonstrate successful
      culture of an embryonic cardiomyoblast line (H9c2 cells) and establishment of an
      in vivo like phenotype within this system.

PMID- 20795704
TI  - Constructed wetlands for wastewater treatment: five decades of experience.
AB  - The first experiments on the use of wetland plants to treat wastewaters were
      carried out in the early 1950s by Dr. Kathe Seidel in Germany and the first full
      scale systems were put into operation during the late 1960s. Since then, the
      subsurface systems have been commonly used in Europe while free water surface
      systems have been more popular in North America and Australia. During the 1970s
      and 1980s, the information on constructed wetland technology spread slowly. But
      since the 1990 s the technology has become international, facilitated by exchange
      among scientists and researchers around the world. Because of the need for more
      effective removal of ammonia and total nitrogen, during the 1990 s and 2000s
      vertical and horizontal flow constructed wetlands were combined to complement
      each other to achieve higher treatment efficiency. Today, constructed wetlands
      are recognized as a reliable wastewater treatment technology and they represent a
      suitable solution for the treatment of many types of wastewater.

PMID- 20795705
TI  - An efficient synthesis of hydantoins via sustainable integration of coupled
      domino processes.
AB  - A highly efficient synthesis of hydantoins has been developed from simple and
      commercially available 1,3-dicarbonyl compounds, ureas, and methyl ketones or
      terminal aryl alkenes. This protocol involves a sustainable integration of two
      coupled domino processes: iodine-promoted synthesis of unsymmetrical 1,4
      enediones (domino I) and the sequential transformation into hydantoins (domino
      II).

PMID- 20795706
TI  - From structure diagrams to visual chemical patterns.
AB  - The intuitive way of chemists to communicate molecules is via two-dimensional
      structure diagrams. The straightforward visual representations are mostly
      preferred to the often complicated systematic chemical names. For chemical
      patterns, however, no comparable visualization standards have evolved so far.
      Chemical patterns denoting descriptions of chemical features are needed whenever
      a set of molecules is filtered for certain properties. The currently available
      representations are constrained to linear molecular pattern languages which are
      hardly human readable and therefore keep chemists without computational
      background from systematically formulating patterns. Therefore, we introduce a
      new visualization concept for chemical patterns. The common standard concept of
      structure diagrams is extended to account for property descriptions and logic
      combinations of chemical features in patterns. As a first application of the new
      concept, we developed the SMARTSviewer, a tool that converts chemical patterns
      encoded in SMARTS strings to a visual representation. The graphic pattern
      depiction provides an overview of the specified chemical features, variations,
      and similarities without needing to decode the often cryptic linear expressions.
      Taking recent chemical publications from various fields, we demonstrate the wide
      application range of a graphical chemical pattern language.

PMID- 20795707
TI  - New flexible toolbox for nanomechanical measurements with extreme precision and
      at very high frequencies.
AB  - We show that the principally two-dimensional (2D) scanning tunneling microscope
      (STM) can be used for imaging of 1D micrometer high free-standing nanowires. We
      can then determine nanowire megahertz resonance frequencies, image their top-view
      2D resonance shapes, and investigate axial stress on the nanoscale. Importantly,
      we demonstrate the extreme sensitivity of electron tunneling even at very high
      frequencies by measuring resonances at hundreds of megahertz with a precision far
      below the angstrom scale.

PMID- 20795708
TI  - Langmuir and Langmuir-Blodgett films of a maleic anhydride derivative: effect of
      subphase divalent cations.
AB  - We report the study of the equilibrium and dynamic properties of Langmuir
      monolayers of poly(styrene-co-maleic anhydride) partial 2-buthoxyethyl ester
      cumene terminated polymer and the effect of the Mg(NO(3))(2) addition in the
      water subphase on the film properties. Results show that the polymer monolayer
      becomes more expanded when the electrolyte concentration in the subphase
      increases. Dense polymer films aggregate at the interface. The aggregates are
      transferred onto silicon wafers using the Langmuir-Blodgett methodology and the
      morphology is observed by AFM. The structure of aggregates depends on the
      subphase composition of the Langmuir film transferred onto the silicon wafer.

PMID- 20795709
TI  - Minimalist end groups for control of absolute helicity in salen- and salophen
      based metallofoldamers.
AB  - (S)-1-Methylindan end groups are effective controllers of absolute helicity in Ni
      salen- and Ni-salophen-based foldamers derived from (R,R)-trans-1,2
      cyclohexanediamine and 1,2-phenylenediamine, respectively. Evidence for the
      helicity of the described complexes was provided through X-ray crystallography
      and study of chiroptical properties in solution. The chiral end groups control
      the absolute sense of helicity for the salen complexes, even in a case where the
      helical bias of the end group is mismatched relative to that of the internal
      diamine.

PMID- 20795710
TI  - Characterization of mononuclear oxygen-centered radical (O(-*)) in Zr(2)O(8)(-)
      cluster.
AB  - Zirconium oxide cluster anions Zr(x)O(y)(-) are prepared by laser ablation and
      are reacted with n-butane in a fast flow reactor under near room temperature
      conditions. A time-of-flight mass spectrometer is used to detect the cluster
      distribution before and after the reactions. Observation of a hydrogen atom
      pickup product Zr(2)O(8)H(-) indicates a C-H activation reaction: Zr(2)O(8)(-) +
      n-C(4)H(10) -> Zr(2)O(8)H(-) + C(4)H(9). Density functional theory calculations
      predict that the oxygen-very-rich cluster Zr(2)O(8)(-) contains one mononuclear
      oxygen-centered radical (O(-)(*)), which leads to a high C-H activation
      reactivity, in agreement with the experiments. This study provides one example
      for how the highly oxidative O(-)(*) radical may be generated by adsorption of
      O(2) onto unreactive metal oxide clusters.

PMID- 20795711
TI  - Hybrid nanoparticle-liposome detection of phospholipase activity.
AB  - A flexible nanoparticle-based phospholipase (PL) assay is demonstrated in which
      the enzymatic substrate is decoupled from the nanoparticle surface. Liposomes are
      loaded with a polypeptide that is designed to heteroassociate with a second
      polypeptide immobilized on gold nanoparticles. Release of this polypeptide from
      the liposomes, triggered by PL, induces a folding-dependent nanoparticle bridging
      aggregation. The colorimetric response from this aggregation enables
      straightforward and continuous detection of PL in the picomolar range. The speed,
      specificity, and flexibility of this assay make it appropriate for a range of
      applications, from point of care diagnostics to high-throughput pharmaceutical
      screening.

PMID- 20795712
TI  - Molecular docking and 3D-QSAR CoMFA studies on indole inhibitors of GIIA secreted
      phospholipase A(2).
AB  - Automated docking allowing a "protein-based" alignment was performed on a set of
      indole inhibitors of the GIIA secreted phospholipase A(2) (GIIA sPLA(2)). A
      correlation between the binding scores and the experimental inhibitory activity
      was observed (r(2) = 0.666, N = 34). All the indole inhibitors were docked in the
      active site of the GIIA sPLA(2) enzyme, and the best score docking pose of each
      inhibitor was used for the "protein-based" alignment of the compounds. A three
      dimensional quantitative structure-activity relationship (3D-QSAR) model was then
      established using the comparative molecular field analysis (CoMFA) method. The
      set of 34 indole inhibitors was divided into two subsets: the training set,
      composed of 26 compounds, and the test set, consisting of eight compounds. The
      robustness and the predictive ability of the generated CoMFA model were examined
      by using the test set. A good correlation (r(2) = 0.997) between predicted and
      experimental inhibitory activity data allows the validation of the CoMFA model.
      Finally, the generated CoMFA model was used for the design and evaluation of new
      compounds. The new designed compounds exert improved predicted inhibitory
      activity and may be a target for the synthesis of new GIIA sPLA(2) indole
      inhibitors.

PMID- 20795714
TI  - Self-assembly of lamellar- and cylinder-forming diblock copolymers in planar
      slits: insight from dissipative particle dynamics simulations.
AB  - We present a dissipative particle dynamics simulation study on nanostructure
      formation of symmetric and asymmetric diblock copolymers confined between planar
      surfaces. We consider symmetric and slightly asymmetric diblock copolymers that
      form lamellar nanostructures in the bulk, and highly asymmetric diblock
      copolymers that form cylindrical nanostructures in the bulk. The formation of the
      diblock copolymer nanostructures confined between the planar surfaces is
      investigated and characterized by varying the separation width and the strength
      of the interaction between the surfaces and the diblock copolymers. Both the slit
      width and the surface interaction strongly influence the phase diagram,
      especially for the asymmetric systems. For the symmetric and slightly asymmetric
      diblock copolymer systems, the confinement primarily affects the orientation of
      the lamellar domains and only marginally influences the domain morphologies.
      These systems form parallel lamellar phases with different number of lamellae,
      and perpendicular and mixed lamellar phases. In a narrow portion of the phase
      diagram, these systems exhibit a parallel perforated lamellar phase, where
      further insight into the appearance of this phase is provided through free-energy
      calculations. The confined highly asymmetric diblock copolymer system shows, in
      addition to nanostructures with parallel and perpendicular cylinders,
      noncylindrical structures such as parallel lamellae and parallel perforated
      lamellae. The formation of the various confined nanostructures is further
      analyzed by calculating structural characteristics such as the mean square end-to
      end distance of the diblock copolymers and the nematic order parameter.

PMID- 20795713
TI  - Assigning stereochemistry to single diastereoisomers by GIAO NMR calculation: the
      DP4 probability.
AB  - GIAO NMR shift calculation has been applied to the challenging task of reliably
      assigning stereochemistry with quantifiable confidence when only one set of
      experimental data are available. We have compared several approaches for
      assigning a probability to each candidate structure and have tested the ability
      of these methods to distinguish up to 64 possible diastereoisomers of 117
      different molecules, using NMR shifts obtained in rapid and computationally
      inexpensive single-point calculations on molecular mechanics geometries without
      time-consuming ab initio geometry optimization. We show that a probability
      analysis based on the errors in each (13)C or (1)H shift is significantly more
      successful at making correct assignments with high confidence than are
      probabilities based on the correlation coefficient and mean absolute error
      parameters. Our new probability measure, which we have termed DP4, complements
      the probabilities obtained from our previously developed CP3 parameter, which
      applies to the case of assigning a pair of diastereoisomers when one has both
      experimental data sets. We illustrate the application of DP4 to assigning the
      stereochemistry or structure of 21 natural products that were originally
      misassigned in the literature or that required extensive synthesis of
      diastereoisomers to establish their stereochemistry.

PMID- 20795715
TI  - Structure and stability of alkane-linked DNA hairpin conjugates.
AB  - The synthesis and properties of three related families of alkane-linked DNA
      hairpins are reported. The first possesses a dodecane linker (C12) and 2-8 AT
      base pairs. The second possesses six AT base pairs and straight chain alkane
      linkers having 8-16 methylenes. The third has three alkane linkers of different
      length and a constant six base-pair stem with alternating A-T bases and a single
      TT step. The spectroscopic properties (UV, CD, and (1)H NMR) and molecular
      modeling are consistent with the formation of base-paired B-DNA structures for
      all hairpins having four or more AT base pairs. The thermal stability of hairpins
      having a C12 linker is greater than that of the commonly used hexa(ethylene
      glycol) linker but less than that of the stilbenediether linker having the same
      AT base-pair domain. Hairpin stability is related to both hydrophobic
      interactions between the linker and the adjacent base pair (stilbene > alkane >
      glycol) and the overall length of the linker. The stability of the alkane-linked
      hairpins having six AT base pairs is greater for a tetradecane linker than for
      either shorter or longer linkers. The good thermal stability of alkane-linked
      hairpins and absence of a chromophore which absorbs in the UV region makes them
      well-suited for studies of the electronic spectra and photochemistry of short
      hairpins having variable base-pair sequences.

PMID- 20795716
TI  - ADP-ribosylation of cross-linked actin generates barbed-end polymerization
      deficient F-actin oligomers.
AB  - Actin filament subunit interfaces are required for the proper interaction between
      filamentous actin (F-actin) and actin binding proteins (ABPs). The production of
      small F-actin complexes mimicking such interfaces would be a significant advance
      toward understanding the atomic interactions between F-actin and its many binding
      partners. We produced actin lateral dimers and trimers derived from F-actin and
      rendered polymerization-deficient by ADP-ribosylation of Arg-177. The degree of
      modification resulted in a moderate reduction in thermal stability. Calculated
      hydrodynamic radii were comparable to theoretical values derived from recent
      models of F-actin. Filament capping capabilities were retained and yielded
      pointed-end dissociation constants similar those of wild-type actin, suggesting
      native or near-native interfaces on the oligomers. Changes in DNase I binding
      affinity under low and high ionic strength suggested a high degree of
      conformational flexibility in the dimer and trimer. Polymer nucleation activity
      was lost upon ADP-ribosylation and rescued upon enzyme-mediated deADP
      ribosylation, or upon binding to gelsolin, suggesting that interactions with
      actin binding proteins can overcome the inhibiting activities of ADP
      ribosylation. The combined strategy of chemical cross-linking and ADP
      ribosylation provides a minimalistic and reversible approach to engineering
      polymerization-deficient F-actin oligomers that are able to act as F-actin
      binding protein scaffolds.

PMID- 20795717
TI  - Contribution of aggregation to the growth mechanism of seeded calcium carbonate
      precipitation in the presence of polyacrylic acid.
AB  - Our work investigates the precipitation mechanism of a seeded calcium carbonate
      reaction, by using cryogenic TEM to observe the early stages of the reaction. The
      early precipitation of a hydrated phase is proposed as an intermediate phase
      before transformation into calcite. Thermodynamic modeling in conjunction with
      pH, surface potential measurements, and colloidal stability modeling demonstrate
      that calcite growth is dominated by agglomeration. This is in agreement with the
      cryogenic TEM observations, which suggest oriented attachment dominates early
      aggregation. The final stage of the reaction is described by a ripening mechanism
      that is significantly inhibited when high concentrations of polyacrylic acid
      (PAA) are used. The different concentrations of PAA lead to significant
      differences in the final particle substructure observed using cross section TEM.
      At low PAA concentrations, single crystal particles result, coherent with the
      proposed early oriented attachment mechanism and interfacial energy calculations.
      A core shell model is proposed for high PAA concentrations, whereas internal
      ripening of nanosized pores has been observed for low PAA concentrations,
      suggesting trapped solvent during the rapid initial particle formation at the
      relatively high supersaturations (S = 30) investigated.

PMID- 20795718
TI  - Creating biomimetic surfaces through covalent and oriented binding of proteins.
AB  - This manuscript describes a novel method for the biofunctionalization of glass
      surfaces with polyhistidine-tagged proteins. The main innovation of this
      methodology consists of the covalent binding between the nitrilotriacetic acid
      (NTA) moiety and the proteins, ensuring not only orientation, but also stability
      of the recombinant proteins on NTA-covered surfaces. In this work, as C-terminal
      polyhistidine tagged cadherin extracellular fragments have been used, this
      methodology guarantees the proper orientation of these proteins, by mimicking
      their insertion into cell plasma membranes. These biofunctionalized surfaces have
      been characterized by confocal microscopy, X-ray photoelectron spectroscopy,
      contact angle, and atomic force microscopy, showing a high density of cadherins
      on the glass surfaces and the stability of the linkage. The prepared materials
      exhibited a high tendency to promote cell spreading, demonstrating the
      functionality of the protein and the high utility of these biomaterials to
      promote cell adhesion events. Interestingly, differences in the cytoskeleton
      organization have been observed in cells adhering to surfaces with no cadherins
      or with nonoriented cadherins, in comparison to surfaces functionalized with well
      oriented cadherins. This method, which allows the robust immobilization of
      polyhistidine tagged proteins due to their covalent binding and with a defined
      orientation, may also find particular usefulness in the making of protein
      biochips, for analysis of protein-protein interactions, as well as structural and
      single-molecule studies.

PMID- 20795719
TI  - Tandem vinylogous 1,2-addition/anionic oxy-Cope reaction leading from butadiene
      sulfone to an orthogonally functionalized bicycle.
AB  - Here we present a transition metal-free synthesis of a rigid, orthogonally
      functionalized bicyclic sulfone, starting from readily available reagents. The
      transformation proceeds via a tandem vinylogous 1,2-addition/anionic oxy-Cope
      sequence, followed by a second vinylogous ketone addition. Stereochemical
      assignments suggest that the anionic oxy-Cope reaction proceeds exclusively
      through a boat-shaped transition state. The product of the two-step sequence can
      be further functionalized through subsequent chemo- and diastereoselective
      transformations, suggesting possible applications in medicinal chemistry or
      materials chemistry.

PMID- 20795720
TI  - 5'-Bis-conjugation of oligonucleotides by amidative oxidation and click
      chemistry.
AB  - A pent-4-ynyl tert-butyl N,N-diisopropyl phosphoramidite was coupled at the 5'
      end of oligonucleotides to give a phosphite triester linkage, which forms an H
      phosphonate diester linkage during treatment with dichloroacetic acid. Then an
      amidative oxidation with CCl(4) in the presence of an amine and a 1,3-dipolar
      cycloaddition with an azide under copper(I) catalysis afforded the bis-conjugated
      oligonucleotides with high efficiency. The introduction of a bromoalkyl group as
      a precursor of azidoalkyl by amidative oxidation allowed the performance of two
      selective 1,3-dipolar cycloadditions.

PMID- 20795721
TI  - A combined spectroscopic and ab initio investigation of phenylacetylene
      methylamine complex. Observation of sigma and pi type hydrogen-bonded
      configurations and fluorescence quenching by weak C-H...N hydrogen bonding.
AB  - Two distinct isomers for the binary complex between phenylacetylene and
      methylamine were observed. The first complex is characterized by the presence of
      a C-H...N hydrogen bond between the acetylenic C-H group and the N atom of
      methylamine. In the second complex the N-H group of methylamine interacts with
      the pi electron density of the benzene ring accompanied by a peripheral
      interaction between the methyl C-H group and the pi electron density of the C=C
      bond. Stabilization energies and Gibbs free energies at the complete basis set
      (CBS) limit of the coupled cluster theory with single, double, and perturbative
      triple excitations [CCSD(T)] suggest that while the C-H...N hydrogen bonded
      complex is the global minimum, the N-H...pi hydrogen bonded complex is a high
      energy local minimum. The formation of the N-H...pi complex could be related to
      kinetic trapping or higher accessibility. Comparison of the laser induced
      fluorescence (LIF) excitation and the one-color-resonant two-photon ionization
      (1C-R2PI) spectra suggests that formation of C-H...N hydrogen bonding leads to
      fluorescence quenching in phenylacetylene, most probably due to dipolar coupling
      in the excited state. The binary complex between the phenylacetylene and
      methylamine shows interesting isomer-dependent fluorescent properties.

PMID- 20795722
TI  - True chemical shift correlation maps: a TOCSY experiment with pure shifts in both
      dimensions.
AB  - Signal resolution in (1)H NMR is limited primarily by multiplet structure. Recent
      advances in pure shift NMR, in which the effects of homonuclear couplings are
      suppressed, have allowed this limitation to be circumvented in 1D NMR, gaining
      almost an order of magnitude in spectral resolution. Here for the first time an
      experiment is demonstrated that suppresses multiplet structure in both domains of
      a homonuclear two-dimensional spectrum. The principle is demonstrated for the
      TOCSY experiment, generating a chemical shift correlation map in which a single
      peak is seen for each coupled relationship, but the principle is general and
      readily extensible to other homonuclear correlation experiments. Such spectra
      greatly simplify manual spectral analysis and should be well-suited to automated
      methods for structure elucidation.

PMID- 20795723
TI  - A metal-organic framework with a covalently prefabricated porous organic linker.
AB  - We report here the synthesis of a metal-organic framework comprising an organic
      cage linker with covalently prefabricated, intrinsic porosity. The network can be
      compared to a porous rock salt structure where the pores are partially filled by
      charge-balancing cations.

PMID- 20795724
TI  - Stereoselective interaction of epimeric naproxen-RGD peptides with human serum
      albumin.
AB  - The dependence of the interaction between human serum albumin (HSA) and two
      epimeric bioconjugates, which contain (S)- or (R)-naproxen (NPX) bound to a
      cyclopentapeptide with an arginine-glycine-aspartate sequence (cRGD), on the
      absolute configuration of the naproxen moiety has been studied using several
      complementary experiments, such as direct physical separation of the unbound
      compound, fluorescence quenching of the protein, circular dichroism, and laser
      flash photolysis. The results were compared with those obtained with model
      compounds, such as (S)- and (R)-NPX, cRGD, and (S)- and (R)-NPX-NHBu amide
      analogues. Fluorescence quenching of Trp-214 in HSA by the naproxen compounds
      (NPXs) revealed lower efficiency for (S)-NPX-RGD in quenching the Trp emission as
      compared to (R)-NPX-cRGD. Laser flash photolysis data together with the
      association constants gave information about the distribution of each compound in
      site I and II, as well as about the lifetime of their triplet excited state
      within each site of HSA. Furthermore, docking modeling agreed with different
      modes of binding of the epimeric bioconjugates. Thus, although both bioconjugates
      bound preferentially to site I, only the NPX moiety of (R)-NPX-cRGD was located
      within the cavity, explaining its efficiency for Trp-214 fluorescence quenching.

PMID- 20795725
TI  - Molybdenum-mediated carbonylation of aryl halides with nucleophiles using
      microwave irradiation.
AB  - A new, efficient, and practical molybdenum-mediated carbonylation of aryl and
      heteroaryl halides with a variety of nucleophiles is described using microwave
      irradiation. A range of reactions illustrating the wide scope of this chemistry
      were carried out and proceeded in good to excellent yields.

PMID- 20795726
TI  - Pyranose ring transition state is derived from cellobiohydrolase I induced
      conformational stability and glycosidic bond polarization.
AB  - Understanding carbohydrate ring pucker is critical to rational design in
      materials and pharmaceuticals. Recently we have generalized our adaptive reaction
      coordinate force biasing method to perform calculations on multidimensional
      reaction coordinates. We termed this the Free Energies from Adaptive Reaction
      Coordinate Forces (FEARCF) method. Using FEARCF in SCC-DFTB QM/MM non-Boltzmann
      simulations, we are able to calculate multidimensional ring pucker free energies
      of conformation. Here we apply this to the six-membered glucopyranose ring
      located in an eight-membered beta 1-4 linked octaose oligosaccharide
      (cellooctaose). The cellooctaose was built following the conformation of the
      saccharides bound to cellobiohydrolase I (CBHI) of Trichoderma reesei as reported
      in the 7CEL crystal structure obtained from the PDB. We calculate the free energy
      of ring puckering of the glucopyranose ring at the -1 position in vacuum, in
      water, and bound to the protein. We find that the protein induces (4)E and
      (4)H(3) conformations that are much more stable than the usually preferred
      (4)C(1) conformer. Furthermore, for the (4)H(3) conformation in the catalytic
      binding domain, there is significant electronic rearrangement that drives the
      structure toward the transition state of the glycosylation reaction.

PMID- 20795727
TI  - New cyclization of 4-oxahepta-1,6-diynes bearing sulfur and selenium functional
      groups.
AB  - New cyclizations of 1-sulfanyl- and -selanyl-4-oxa-1,6-heptadiynes using sodium
      alkoxide or thiolates provided 4-alkoxymethyl-3-phenylsulfanyl- and 3,4
      bis(sulfanylmethyl)furans in high yields.

PMID- 20795728
TI  - Hierarchical nanocomposites of polyaniline nanowire arrays on graphene oxide
      sheets with synergistic effect for energy storage.
AB  - We introduced a facile method to construct hierarchical nanocomposites by
      combining one-dimensional (1D) conducting polyaniline (PANI) nanowires with 2D
      graphene oxide (GO) nanosheets. PANI nanowire arrays are aligned vertically on GO
      substrate. The morphologies of PANI nanowires can be controlled by adjusting the
      ratios of aniline to GO, which are attributed to different nucleation processes.
      The hierarchical nanocomposite structures of PANI-GO were further proved by UV
      vis, FTIR, and XRD measurements. The hierarchical nanocomposite possessed higher
      electrochemical capacitance and better stability than each individual component
      as supercapacitor electrode materials, showing a synergistic effect of PANI and
      GO. This study will further guide the preparation of functional nanocomposites by
      combining different dimensional nanomaterials.

PMID- 20795729
TI  - Nanoelectromechanical resonator arrays for ultrafast, gas-phase chromatographic
      chemical analysis.
AB  - Miniaturized gas chromatography (GC) systems can provide fast, quantitative
      analysis of chemical vapors in an ultrasmall package. We describe a chemical
      sensor technology based on resonant nanoelectromechanical systems (NEMS) mass
      detectors that provides the speed, sensitivity, specificity, and size required by
      the microscale GC paradigm. Such NEMS sensors have demonstrated detection of
      subparts per billion (ppb) concentrations of a phosphonate analyte. By combining
      two channels of NEMS detection with an ultrafast GC front-end, chromatographic
      analysis of 13 chemicals was performed within a 5 s time window.

PMID- 20795730
TI  - Total synthesis of rhazinilam: axial to point chirality transfer in an
      enantiospecific Pd-catalyzed transannular cyclization.
AB  - A total synthesis of rhazinilam based on a transannular cyclization strategy is
      described. Using a Heck reaction, the axial chirality of a halogenated 13
      membered lactam can be exploited to create the quaternary chiral stereogenic
      center in the target molecule with high enantiospecificity.

PMID- 20795731
TI  - The tail wagging the dog: insights into catalysis in R67 dihydrofolate reductase.
AB  - Plasmid-encoded R67 dihydrofolate reductase (DHFR) catalyzes a hydride transfer
      reaction between substrate dihydrofolate (DHF) and its cofactor, nicotinamide
      adenine dinucleotide phosphate (NADPH). R67 DHFR is a homotetramer that exhibits
      numerous characteristics of a primitive enzyme, including promiscuity in binding
      of substrate and cofactor, formation of nonproductive complexes, and the absence
      of a conserved acid in its active site. Furthermore, R67's active site is a pore,
      which is mostly accessible by bulk solvent. This study uses a computational
      approach to characterize the mechanism of hydride transfer. Not surprisingly,
      NADPH remains fixed in one-half of the active site pore using numerous
      interactions with R67. Also, stacking between the nicotinamide ring of the
      cofactor and the pteridine ring of the substrate, DHF, at the hourglass center of
      the pore, holds the reactants in place. However, large movements of the p
      aminobenzoylglutamate tail of DHF occur in the other half of the pore because of
      ion pair switching between symmetry-related K32 residues from two subunits. This
      computational result is supported by experimental results that the loss of these
      ion pair interactions (located >13 A from the center of the pore) by addition of
      salt or in asymmetric K32M mutants leads to altered enzyme kinetics [Hicks, S.
      N., et al. (2003) Biochemistry 42, 10569-10578; Hicks, S. N., et al. (2004) J.
      Biol. Chem. 279, 46995-47002]. The tail movement at the edge of the active site,
      coupled with the fixed position of the pteridine ring in the center of the pore,
      leads to puckering of the pteridine ring and promotes formation of the transition
      state. Flexibility coupled to R67 function is unusual as it contrasts with the
      paradigm that enzymes use increased rigidity to facilitate attainment of their
      transition states. A comparison with chromosomal DHFR indicates a number of
      similarities, including puckering of the nicotinamide ring and changes in the DHF
      tail angle, accomplished by different elements of the dissimilar protein folds.

PMID- 20795732
TI  - Organocatalytic asymmetric synthesis of chiral pyrrolizines by cascade conjugate
      addition-aldol reactions.
AB  - As the first N-centered heteroaromatic nucleophile for organocatalytic cascade
      reactions, pyrroles underwent the enantio- and diastereoselective organocatalytic
      cascade conjugate addition-aldol reactions of alpha,beta-unsaturated aldehydes
      that afford the highly functionalized chiral pyrrolizines bearing three
      consecutive stereocenters in good yields, high enantioselectivities (90-98% ee),
      and excellent diastereoselectivities (>20:1 dr in all cases).

PMID- 20795733
TI  - Substitution of Ala for Tyr567 in RB69 DNA polymerase allows dAMP and dGMP to be
      inserted opposite Guanidinohydantoin .
AB  - Continuous oxidative damage inflicted on DNA produces 7,8-dihydro-8-oxoguanine (8
      oxoG), a commonly occurring lesion that can potentially cause cancer by producing
      G -> T transversions during DNA replication. Mild oxidation of 8-oxoG leads to
      the formation of hydantoins, specifically guanidinohydantoin (Gh) and
      spiroiminodihydantoin (Sp), which are 100% mutagenic because they encode almost
      exclusively the insertion of dAMP and dGMP (encoding G -> T and G -> C
      transversions, respectively). The wild-type (wt) pol alpha family DNA polymerase
      from bacteriophage RB69 (RB69pol) inserts dAMP and dGMP with low efficiency when
      situated opposite Gh. In contrast, the RB69pol Y567A mutant inserts both of these
      dNMPs opposite Gh with >100-fold higher efficiency than wt. We now report the
      crystal structure of the "closed" preinsertion complex for the Y567A mutant with
      dATP opposite a templating Gh (R-configuration) in a 13/18mer primer-template
      (P/T) at 2.0 A resolution. The structure data reveal that the Y to A substitution
      provides the nascent base pair binding pocket (NBP) with the flexibility to
      accommodate Gh by allowing G568 to move in the major-to-minor groove direction of
      the P/T. Thus, Gh is rejected as a templating base by wt RB69pol because G568 is
      inflexible, preventing Gh from pairing with the incoming dATP or dGTP base.

PMID- 20795735
TI  - Validation of in vitro cell-based human blood-brain barrier model using clinical
      positron emission tomography radioligands to predict in vivo human brain
      penetration.
AB  - We have evaluated a novel in vitro cell-based human blood-brain barrier (BBB)
      model that could predict in vivo human brain penetration for compounds with
      different BBB permeabilities using the clinical positron emission tomography
      (PET) data. Comparison studies were also performed to demonstrate that the in
      vitro cell-based human BBB model resulted in better predictivity over the
      traditional permeability model in discovery organizations, Caco-2 cells. We
      evaluated the in vivo BBB permeability of [(18)F] and [(11)C]-compounds in humans
      by PET imaging. The in vivo plasma-brain exchange parameters used for comparison
      were determined in humans by PET using a kinetic analysis of the radiotracer
      binding. For each radiotracer, the parameters were determined by fitting the
      brain kinetics of the radiotracer using a two-tissue compartment model of the
      ligand-receptor interaction. Bidirectional transport studies with the same
      compounds as in in vivo studies were carried out using the in vitro cell-based
      human BBB model as well as Caco-2 cells. The in vitro cell-based human BBB model
      has important features of the BBB in vivo and is suitable for discriminating
      between CNS and non-CNS marketed drugs. A very good correlation (r(2) = 0.90; P <
      0.001) was demonstrated between in vitro BBB permeability and in vivo
      permeability coefficient. In contrast, a poor correlation (r(2) = 0.17) was
      obtained between Caco-2 data and in vivo human brain penetration. This study
      highlights the potential of this in vitro cell-based human BBB model in drug
      discovery and shows that it can be an extremely effective screening tool for CNS
      programs.

PMID- 20795734
TI  - Characterization of the interaction of beta-amyloid with transthyretin monomers
      and tetramers.
AB  - beta-Amyloid (Abeta) is the main protein component of the amyloid plaques
      associated with Alzheimer's disease. Transthyretin (TTR) is a homotetramer that
      circulates in both blood and cerebrospinal fluid. Wild-type (wt) TTR amyloid
      deposits are linked to senile systemic amyloidosis, a common disease of aging,
      while several TTR mutants are linked to familial amyloid polyneuropathy. Several
      recent studies provide support for the hypothesis that these two amyloidogenic
      proteins interact, and that this interaction is biologically relevant. For
      example, upregulation of TTR expression in Tg2576 mice was linked to protection
      from the toxic effects of Abeta deposition [Stein, T. D., and Johnson, J. A.
      (2002) J. Neurosci. 22, 7380-7388]. We examined the interaction of Abeta with wt
      TTR as well as two mutants: F87M/L110M, engineered to be a stable monomer, and
      T119M, a naturally occurring mutant with a tetrameric stability higher than that
      of the wild type. On the basis of enzyme-linked immunoassays as well as cross
      linking experiments, we conclude that Abeta monomers bind more to TTR monomers
      than to TTR tetramers. The data further suggest that TTR tetramers interact
      preferably with Abeta aggregates rather than Abeta monomers. Through tandem mass
      spectrometry analysis of cross-linked TTR-Abeta fragments, we identified the A
      strand, in the inner beta-sheet of TTR, as well as the EF helix, as regions of
      TTR that are involved with Abeta association. Light scattering and electron
      microscopy studies demonstrate that the outcome of the TTR-Abeta interaction
      strongly depends on TTR quaternary structure. While TTR tetramers may modestly
      enhance aggregation, TTR monomers decidedly arrest Abeta aggregate growth. These
      data provide important new insights into the nature of TTR-Abeta interactions.
      Such interactions may regulate TTR-mediated protection against Abeta toxicity.

PMID- 20795736
TI  - Prediction of extra virgin olive oil varieties through their phenolic profile.
      Potential cytotoxic activity against human breast cancer cells.
AB  - The aim of this work was to develop a rapid resolution liquid chromatography
      coupled to electrospray ionization time-of-flight mass spectrometry (RRLC-ESI-TOF
      MS) method followed by tetrazolium salt (MTT)-based cell viability assays for
      qualitative and quantitative classification of extra virgin olive oil (EVOO)
      varieties by phenolic and other polar compound contents as well as for rapid
      characterization of putative cytotoxic activities against human cancer cells.
      Five different Spanish EVOO varieties were analyzed, and RRLC-ESI-TOF-MS method
      was applied for qualitative and quantitative identification of most important
      phenolic compounds. We finally employed MTT-based cell viability protocol to
      assess the effects of crude EVOO phenolic extracts (PEs) on the metabolic status
      of cultured SKBR3 human breast cancer cells. MTT-based cell viability assays
      revealed a wide range of breast cancer cytotoxic potencies among individual crude
      PE obtained from EVOO monovarietals. Remarkably, breast cancer cell sensitivity
      to crude EVOO-PEs was up to 12 times higher in secoiridoids enriched-PE than in
      secoiridoids-low/null EVOO-PE.

PMID- 20795738
TI  - Mechanism insight into the cyanide-catalyzed benzoin condensation: a density
      functional theory study.
AB  - The reaction mechanism of the cyanide-catalyzed benzoin condensation without
      protonic solvent assistance has been studied computationally for the first time
      employing the density functional theory (B3LYP) method in conjunction with 6
      31+G(d,p) basis set. Four possible pathways have been investigated. A new
      proposed pathway on the basis of the Lapworth mechanism is determined to be the
      dominant pathway in aprotic solvent, in which the formation of the Lapworth's
      cyanohydrin intermediate is a sequence including three steps assisted by
      benzaldehyde, clearly manifesting that the reaction can take place in aprotic
      solvents such as DMSO. In this favorable pathway with six possible transition
      states located along the potential energy surface, the reaction of the
      cyanide/benzaldehyde complex with another benzaldehyde to afford an alpha-hydroxy
      ether is the rate-determining dynamically with the activation free energy barrier
      of 26.9 kcal/mol, and the step to form cyanohydrin intermediate from alpha
      hydroxy ether is partially rate-determining for its relatively significant
      barrier 20.0 kcal/mol.

PMID- 20795737
TI  - Structure-independent analysis of the breadth of the positional distribution of
      disordered groups in macromolecules from order parameters for long, variable
      length vectors using NMR paramagnetic relaxation enhancement.
AB  - Quantitative information regarding structurally disordered groups is crucial for
      a complete understanding of the relationship between structure, dynamics, and
      function in biological macromolecules. Experimental analysis, however, of the
      positional distribution of disordered groups in the macromolecular frame is
      extremely difficult. While NMR order parameters, S(2), for fixed-length bond
      vectors such as N-H and C-H are commonly used for investigations of
      conformational dynamics of macromolecules, these order parameters provide only
      angular information about internal motions and are totally insensitive to
      translational motions. Although analysis of S(2) for bond vectors permits
      identification of disordered groups in macromolecules, this type of order
      parameter cannot provide any information about the distribution radii of
      disordered groups. Here we describe an NMR approach to directly determine the
      distribution radius of a disordered group independent of any structural
      knowledge. This approach makes use of order parameters for long, variable-length
      vectors (including proton-paramagnetic center and proton-proton vectors) between
      a disordered group and a rigid portion of the macromolecule. We demonstrate the
      application of this formalism to paramagnetic relaxation enhancement vectors. In
      addition, the potential utility of the same formalism to (1)H-(1)H cross
      relaxation rates is considered as an alternative approach for analyzing the
      breadth of the positional distribution of disordered groups.

PMID- 20795739
TI  - Detection of weak intramolecular interactions in Ru(3)(CO)(12) by topological
      analysis of charge density distributions.
AB  - The presence of weak intramolecular interactions among the axial carbon atoms in
      Ru(3)(CO)(12), previously detected by topological analysis of the 120 K X-ray
      derived charge density, has been here confirmed by theoretical calculations on
      the isolated, "gas-phase" molecule, using the all-electron B97D/3-21G approach,
      as well as by further experimental determinations of higher accuracy on data
      collected at 100 K. The importance of using density functional theory (DFT)
      approaches where dispersion terms are explicitly added to the usual Kohn-Sham
      energy to reproduce such weak intramolecular interactions has been evidenced.
      This result confirms the multipole approach as an efficient and sensitive tool to
      extract fine details of electron density distributions.

PMID- 20795740
TI  - Structure and relative potency of several karlotoxins from Karlodinium veneficum.
AB  - The karlotoxins are a family of amphidinol-like compounds that play roles in
      avoiding predation and in prey capture for the toxic dinoflagellate Karlodinium
      veneficum. The first member of the toxin group to be reported was KmTx 1 (1), and
      here we report an additional five new members of this family (3-7) from the same
      strain. Of these additional compounds, KmTx 3 (3) differs from KmTx 1 (1) in
      having one less methylene group in the saturated portion of its lipophilic arm.
      In addition, 64-E-chloro-KmTx 3 (4) and 10-O-sulfo-KmTx 3 (5) were identified.
      Likewise, 65-E-chloro-KmTx 1 (6) and 10-O-sulfo-KmTx 1 (7) were also isolated.
      Comparison of the hemolytic activities of the newly isolated compounds to that of
      KmTx 1 shows that potency correlates positively with the length of the lipophilic
      arm and is disrupted by sulfonation of the polyol arm.

PMID- 20795741
TI  - Polyacetylenes from the roots of Polyalthia debilis.
AB  - Six new linear polyacetylenic C25 and C27 acetogenins (1-6), named debilisones A
      F, have been isolated from a methanol extract of roots of Polyalthia debilis.
      Structures of these compounds were determined by spectroscopic techniques. The
      absolute configuration at C-17 of 2 was assigned by the modified Mosher's method.
      Compounds 2, 3, and 5 exhibited moderate antimycobacterial activity against
      Mycobacterium tuberculosis with MIC values of 25.0, 12.5, and 25.0 microg/mL,
      respectively.

PMID- 20795742
TI  - Notoamide O, a structurally unprecedented prenylated indole alkaloid, and
      notoamides P-R from a marine-derived fungus, Aspergillus sp.
AB  - Notoamides O-R were isolated from a marine-derived Aspergillus sp. Notoamide O
      possesses a novel hemiacetal/hemiaminal ether functionality hitherto unknown
      among this family of prenylated indole alkaloids. The structure represents an
      unusual branch point for the oxidative modification of other members in the
      family of prenylated indole alkaloids in the biogenetic pathway.

PMID- 20795744
TI  - A novel one-pot approach of hexahydropyrrolo[2,3-b]indole nucleus by a cascade
      addition/cyclization strategy: synthesis of (+/-)-esermethole.
AB  - A practical and efficient synthesis of 3-substituted hexahydropyrrolo[2,3
      b]indole is described. The addition/cyclization of 3-substituted indoles with
      alpha,beta-dehydroamino esters in the presence of a Lewis acid provides
      hexahydropyrrolo[2,3-b]indole adducts in good yields and stereoselectivities.
      This approach has been applied to the concise synthesis of esermethole employing
      an appropriately substituted indole and an N-acyl dehydroamino ester.

PMID- 20795743
TI  - Eucapsitrione, an anti-Mycobacterium tuberculosis anthraquinone derivative from
      the cultured freshwater cyanobacterium Eucapsis sp.
AB  - Eucapsitrione (1), an anthraquinone derivative with an indeno-anthracene-trione
      skeleton, was isolated from the cyanobacterium Eucapsis sp. (UTEX 1519) by
      bioassay-guided fractionation. The chemical structure was determined by analyzing
      MS and 1D and 2D NMR spectroscopic data. Eucapsitrione (1) showed anti
      Mycobacterium tuberculosis activity in the microplate Alamar blue assay and low
      oxygen-recovery assay with MIC values of 3.1 and 6.4 microM, respectively.

PMID- 20795746
TI  - Fused bispentacenequinone and its unexpected Michael addition.
AB  - Fused bispentacenequinone 2 was synthesized by photocyclization of
      bispentacenequinone 1. Unusual regioselective Michael addition was observed for 2
      when excess aryl Grignard reagent was used. Subsequent acidification and
      oxidation in air gave diaryl-substituted bispentacenequinone 3. Tetra-aryl
      substituted fused bispentacenequinone 4 was obtained from 3 after the second
      Michael addition followed by oxidation in air.

PMID- 20795745
TI  - Synthesis of the bis-tetrahydropyran core of amphidinol 3.
AB  - A convergent synthesis of the C31-C52 bis-tetrahydropyran core of the natural
      product amphidinol 3 is reported. A common intermediate was synthesized from d
      tartaric acid utilizing an asymmetric glycolate alkylation/ring-closing
      metathesis sequence to construct the THP rings. Differential elaboration of the
      common intermediate allowed the synthesis of two distinct coupling partners which
      were joined through a modified Horner-Wadsworth-Emmons olefination to provide the
      bis-tetrahydropyran core.

PMID- 20795747
TI  - Direct synthesis of quinazolines through copper-catalyzed reaction of aniline
      derived benzamidines.
AB  - A novel synthesis of 2-phenyl-4-[(triisopropylsilyl)methyl]quinazolines from
      monosubstituted arenes has been developed. Treatment of N-phenylbenzamidines with
      5-nitro-1-[(triisopropylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one and K(2)CO(3) in
      the presence of a catalytic amount of CuBr in benzene gives 2-phenyl-4
      [(triisopropylsilyl)methyl]quinazolines in moderate to good yields.

PMID- 20795748
TI  - "Carbon dichloride": dihalocarbenes sixty years after Hine.
AB  - We describe new syntheses of dichlorodiazirine, difluorodiazirine, and
      chlorofluorodiazirine. From these precursors, laser flash photolysis enables the
      generation of CCl(2), CF(2), and CClF. We describe the formation and chemistry of
      bromodichloromethide carbanion from CCl(2), the ambiplilicity of CCl(2), the
      complexation of CCl(2) by aromatic ethers, and the kinetics and activation
      parameters attending the additions of CCl(2), CF(2), and CClF to several alkenes.

PMID- 20795749
TI  - Palladium-catalyzed cascade aryl addition/intramolecular lactonization of
      phthalaldehyde to access 3-aryl- and alkenylphthalides.
AB  - A palladium-catalyzed addition of arylboronic acids to phthalaldehyde, followed
      by an intramolecular lactonization to access 3-substituted phthalides, is
      described. The procedure tolerates a series of functional groups, such as
      methoxyl, fluoro, chloro, and trifluoromethyl groups. It represents a procedure
      for the synthesis of 3-substituted phthalides.

PMID- 20795750
TI  - Dynamic changes in the proteome of Synechocystis 6803 in response to CO(2)
      limitation revealed by quantitative proteomics.
AB  - Cyanobacteria developed efficient carbon concentrating mechanisms which
      significantly improve the photosynthetic performance and survival of cells under
      limiting CO(2) conditions. Dynamic changes of the Synechocystis proteome to CO(2)
      limitation were investigated using shotgun LC-MS/MS approach with isobaric tag
      for relative and absolute quantification (iTRAQ) technique. Synechocystis cells
      grown at high (3%) CO(2) were shifted to air-level CO(2) followed by protein
      extraction after 6, 24, and 72 h. About 19% of the cyanobacterial proteome was
      identified and the expression changes were quantified for 17% of theoretical
      ORFs. For 76 proteins, up- or down-regulation was found to be significant (more
      than 1.5 or less than 0.7). Major changes were observed in proteins participating
      in inorganic carbon uptake, CO(2) fixation, nitrogen transport and assimilation,
      as well as in the protection of the photosynthetic machinery from excess of
      light. Further, a number of hypothetical proteins with unknown functions were
      discovered. In general, the cells appear to acclimate to low CO(2) without a
      significant stress since the stress-related molecular chaperones were down
      regulated and only a minor decline was detected for proteins of phycobilisomes,
      photosynthetic complexes, and translation machinery. The results of iTRAQ
      experiment were validated by the Western blot analysis for selected proteins.

PMID- 20795751
TI  - Meningococcal quadrivalent (serogroups A, C, w135, and y) conjugate vaccine
      (Menveo): in adolescents and adults.
AB  - Menveo is a quadrivalent meningococcal polysaccharide conjugate vaccine
      containing the four Neisseria meningitidis capsular polysaccharides, A, C, W135,
      and Y, each conjugated to the mutant diphtheria toxin, known as crossreactive
      material 197 (CRM(197)). Administration of a single dose of the Menveo vaccine
      elicited a strong immune response against all four vaccine serogroups in
      adolescents and adults in randomized, single- or multicenter, phase II or III
      trials. In adolescents, Menveo was generally more immunogenic against vaccine
      serogroups than the polysaccharide conjugate vaccine Menactra or the unconjugated
      polysaccharide vaccine Menomune, in terms of seroresponse and/or seroprotection
      rates and geometric mean titers (GMTs) 1 month post-vaccination in two phase II
      or III studies. In two phase III trials in adults aged 19-55 years, the
      immunogenicity of Menveo was generally noninferior or superior to that of
      Menactra against all four vaccine serogroups, with regard to
      seroresponse/seroprotection rates, and GMTs 1 month after vaccination. Moreover,
      an exploratory arm of one of these studies suggested Menveo was at least as
      immunogenic as Menomune in adults aged 56-65 years. Longer term, the
      immunogenicity of Menveo persisted for 12-22 months post-vaccination in the
      adolescent studies, with the vaccine generally remaining at least as immunogenic
      as Menactra or Menomune. Coadministration of Menveo with a combined tetanus,
      reduced diphtheria, and acellular pertussis (Tdap) vaccine or Tdap and human
      papillomavirus vaccines generally did not affect the immunogenicity of these
      vaccines in adolescents and young adults in two additional randomized, single- or
      multicenter, phase III studies. The tolerability profile of Menveo was generally
      similar to that of the comparator vaccines Menactra or Menomune in adults and
      adolescents, and few Menveo recipients experienced serious adverse events within
      30 days or 6 months post-vaccination.

PMID- 20795752
TI  - Spotlight on DTPa-HBV-IPV/Hib Vaccine (Infanrix hexa).
AB  - Infanrix hexa, administered intramuscularly, is a diphtheria, tetanus, acellular
      pertussis, hepatitis B (HBV), inactivated poliomyelitis and Haemophilus
      influenzae type b (Hib) conjugate vaccine, indicated for primary and booster
      vaccination of infants. Infanrix hexa should be administered as a two- or three
      dose primary vaccination course in infants aged < or =6 months, followed by
      booster vaccination between 11 and 18 months of age, with an interval of at least
      6 months between the last dose of primary vaccination and the booster dose. This
      spotlight reviews the immunogenicity and protective effectiveness, as well as the
      reactogenicity and safety of Infanrix hexa. Infanrix hexa as primary and booster
      vaccination was safe and highly immunogenic for all its component
      toxoids/antigens in infants aged <2 years, regardless of vaccination schedules.
      Its immunogenicity and safety profiles were generally similar to those of
      currently available vaccines, the diphtheria, tetanus and acellular pertussis
      based pentavalent vaccines plus monovalent HBV or Hib vaccines. In large clinical
      studies, Infanrix hexa elicited a strong immune response against vaccine
      toxoids/antigens, as indicated by high seroprotection/seropositivity/vaccine
      response rates and geometric mean titers. Moreover, antibodies against vaccine
      toxoids/antigens persisted for up to a mean of approximately 6 years after
      booster vaccination, and the vaccine induced long-term immune memory against
      hepatitis B surface antigen and Hib antigen. A strong immune response against
      Infanrix hexa toxoids/antigens after primary vaccination was also induced in
      infants who had received a dose of HBV vaccine at birth and in pre-term infants,
      although the response in the latter group was somewhat lower than that in full
      term infants. In addition, when coadministered with other childhood vaccines, the
      immunogenicity of Infanrix hexa or that of the concomitantly administered vaccine
      was generally not altered. Hexavalent vaccines, including Infanrix hexa, were
      protective against invasive Hib disease; Infanrix hexa is also expected to be
      protective against pertussis. Most solicited local and general symptoms with
      Infanrix hexa were mild to moderate in intensity and the vaccine was associated
      with few unsolicited adverse events. Available clinical data from more than 10
      years' experience with the vaccine suggest that Infanrix hexa as primary and
      booster vaccination is a safe and useful option for providing protection against
      the common childhood diseases of diphtheria, tetanus, poliomyelitis, pertussis,
      hepatitis B and invasive Hib disease.

PMID- 20795753
TI  - Therapeutic approaches to multiple sclerosis: an update on failed, interrupted,
      or inconclusive trials of neuroprotective and alternative treatment strategies.
AB  - Currently approved multiple sclerosis (MS) therapeutics have a mainly anti
      inflammatory mode of action. However, a number of promising clinical trials have
      been initiated that either focus on neuroprotection or follow completely
      different treatment strategies. So far, all of these clinical trials have failed
      to show efficacy or had to be halted prematurely because of unexpected adverse
      events. Some others show results that are of unknown significance with regard to
      a reliable assessment of true efficacy versus safety. For example, trials
      addressing the highly promising sodium channel blockers are under close
      observation because of potential adverse effects after drug withdrawal.
      Previously failed therapeutic approaches in MS have indicated that there are
      discrepancies between the theoretical expectations and practical outcomes of
      different compounds. Learning from these failures helps to optimize future study
      designs and to reduce risks to patients. This review summarizes trials on MS
      treatments since 2001 that failed or were interrupted, attempts to analyze the
      underlying reasons for failure, and discusses the implications for our current
      view of MS pathogenesis, clinical practice, and the design of future studies. In
      order to maintain clarity, this review focuses on neuroprotective and various
      other treatment strategies. Clinical trials addressing anti-inflammatory research
      strategies are presented elsewhere.

PMID- 20795754
TI  - Carbosilane dendrimers to transfect human astrocytes with small interfering RNA
      targeting human immunodeficiency virus.
AB  - BACKGROUND: HIV infection of the CNS is the principle cause of HIV-associated
      dementia in adults and encephalopathy in children. Gene therapy techniques such
      as small interfering RNA (siRNA) possess great potential in drug development, but
      first they must overcome the key obstacle of reaching the interior of the
      affected cells. A successful delivery vector for anti-HIV drugs that is capable
      of crossing the blood-brain barrier (BBB) could provide a way of addressing this
      issue. Non-viral vectors such as dendrimers offer a means for effectively
      delivering and transfecting siRNA to the target cells. OBJECTIVE: To evaluate the
      application of gene therapy for reducing HIV replication in human astrocytes.
      METHODS: We used the 2G-NN16 amino-terminated carbosilane dendrimer as a method
      for delivering siRNA to HIV-infected human astrocytes. We tested the cytotoxicity
      in human astrocytoma cells caused by 2G-NN16 and dendriplexes formed with siRNA
      (siRNA/2G-NN16) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium-bromide
      (MTT) and lactate dehydrogenase assays. The ability to transfect human astrocytes
      with siRNA/2G-NN16 dendriplexes was tested by flow cytometry and
      immunofluorescence microscopy. To assess the potential capability of siRNA/2G
      NN16 dendriplexes for crossing the BBB, we used an in vitro transcytosis assay
      with bovine brain microvascular endothelial cells. HIV-1 inhibition assays using
      2G-NN16 and siRNA/2G-NN16 dendriplexes were determined by quantification of the
      viral load from culture supernatants of the astrocytes. RESULTS: A gradual time
      controlled degradation of the 2G-NN16 dendrimer and liberation of its siRNA cargo
      between 12 and 24 hours was observed via gel electrophoresis. There was no
      cytotoxicity in HIV-infected or non-infected human astrocytoma cells when treated
      with up to 24 microg/mL of 2G-NN16 dendrimer or siRNA/2G-NN16 dendriplexes, and
      siRNA/2G-NN16 dendriplexes were seen to successfully transfect human astrocytes
      even after crossing an in vitro BBB model. More interestingly, transfected siRNA
      was observed to exert a biologic effect, as dendriplexes were shown to down
      regulate the housekeeping gene GAPDH and to reduce replication of HIV-1 strains
      X4-HIV NL4-3 and R5-HIV BaL in human astrocytes. CONCLUSIONS: The 2G-NN16
      dendrimer successfully delivers and transfects siRNA to HIV-infected human
      astrocytes and achieves gene silencing without causing cytotoxicity.

PMID- 20795755
TI  - Assessment of biosand filter performance in rural communities in southern coastal
      Nicaragua: an evaluation of 199 households.
AB  - INTRODUCTION: Lack of access to safe drinking water is a major health issue for
      more than one billion people globally. In areas where community-wide water
      treatment is not possible, point-of-use (POU) solutions are necessary. The
      biosand filter (BSF) is one of several such POU technologies available to treat
      water in the home to reduce the risk of infection. This study was conducted to
      evaluate the use and performance of BSFs in the rural communities surrounding San
      Juan del Sur, Nicaragua. Approximately 600 filters had been installed in this
      area over the preceding 2 years by local workers supported by US and Canadian
      NGOs. METHODS: This field study was conducted In July and August 2009.
      Unannounced household visits were carried out by US volunteers supported by a
      local interpreter and driver. Visits were made to a convenience sample of 199
      households where BSFs had been in place for an average of 12 months. Water for
      analysis was collected from wells, filter spouts and storage buckets and an 11
      item questionnaire was administered. Laboratory analyses were performed on water
      samples using the membrane filtration method to determine Escherichia coli colony
      forming units (CFUs). RESULTS: Forty-five of 199 households visited had
      discontinued use of their BSF. In the 154 households tested, median CFU of E.
      coli per 100 mL of water from the source, filter spout and storage vessel were
      313, 72, and 144, respectively. Median bacterial removal efficiency for the
      filters was 80%. Although biosand filtration reduced CFUs in 74% of households in
      which it was used, in only 26 cases (17%) did it reduce CFUs to <10 CFUs/100 mL.
      Recontamination was an important problem and reduced the overall efficacy (from
      well to storage bucket) to 48%. Participants were generally satisfied with their
      filter's performance, citing improved health and better tasting water.
      CONCLUSION: Water quality testing of BSFs deployed in the field showed results
      somewhat inferior to previous reports. Possible explanations include lack of use
      of best practices and the inclusion of some filers in the analysis that may not
      have been in active use. Despite these results and high rates of recontamination
      in the storage bucket, most households members were pleased with their filters
      and claimed that their use had enhanced their health. This inconsistency could be
      due to inaccurate responses to the questionnaire for purposes of secondary gain.

PMID- 20795756
TI  - Prophylactic penicillin by the full moon: a novel approach in Central Australia
      that may help to reduce the risk of rheumatic heart disease.
AB  - INTRODUCTION: Uptake of penicillin prophylaxis to prevent recurrent rheumatic
      fever and its sequela rheumatic heart disease (RHD) is not optimal in the
      Northern Territory of Australia. The Full Moon Strategy (the Strategy) was
      introduced in the Central Australian region in June 2006 to improve the uptake of
      prophylactic penicillin: clients and healthcare workers were encouraged to use
      the full moon as a cue for the timing of the 4 weekly prophylactic penicillin
      injection. OBJECTIVE: To determine the impact and effectiveness of the Strategy
      on knowledge and uptake of benzathine penicillin prophylaxis for clients at risk
      of RHD, and for primary healthcare workers in Central Australia. METHODS: Clients
      at risk of RHD in four remote Aboriginal communities and the town camps of Alice
      Springs were identified from the RHD database. Consenting clients or their carers
      were interviewed about their knowledge of the Strategy and the health promotional
      tools used. Their healthcare records were then reviewed for prophylaxis uptake 2
      years prior to and 2 years following the introduction of the Strategy. Primary
      healthcare workers in the four remote communities who were available at the time
      of the study visit were interviewed about their knowledge and use of the Strategy
      and the health promotional tools. RESULTS: Fifty RHD clients and 19 healthcare
      workers were interviewed. Most were aware of the flipchart but less than half
      knew of the calendar poster, hand-held card or radio advertisement. Prophylaxis
      uptake increased significantly from 47% in the 2 years prior to the introduction
      of the Strategy, to 57% 2 years after the Strategy was introduced. CONCLUSION:
      Introduction of the Strategy coincided with an improvement in uptake of
      prophylaxis but not around the time of the full moon. Uptake of benzathine
      penicillin remains inadequate and further innovative measures are needed to
      control rheumatic fever and its sequela in Aboriginal and Torres Strait Islander
      people.

PMID- 20795757
TI  - Adipose tissue-derived stem cells show both immunogenic and immunosuppressive
      properties after chondrogenic differentiation.
AB  - BACKGROUND AIMS: The chondrogenic differentiation potential of mesenchymal
      stromal cells (MSC), as well as their immunosuppressive properties, have been
      studied extensively. So far, only a few studies have addressed the question of
      whether MSC still retain their immunosuppressive qualities after
      transdifferentiation. In particular, the expression of immunogenic markers, such
      as human leukocyte antigen (HLA)-DR, after differentiation has never been
      investigated. METHODS: Chondrogenic transdifferentiation was induced in human
      adipose tissue-derived stem cell (ADSC) pellet cultures derived from 10 different
      patients, using 10 ng/mL transforming growth factor (TGF)-beta3. Samples were
      harvested over a time-course of 28 days and analyzed by immunohistochemistry and
      reverse transcription (RT)-polymerase chain reaction (PCR). The cytokine levels
      in the supernatants of the samples were measured semi-quantitatively by dot-blots
      and quantitatively by enzyme-linked immunosorbant assays (ELISA). RESULTS:
      Undifferentiated ADSC were negative for chondrogenic markers, as well as HLA-ABC
      and HLA-DR epitopes in immunofluorescence. In contrast, TGF-beta3-induced pellet
      cultures showed both expression of chondrogenic differentiation markers, such as
      transcription factor 9 (Sox 9), collagen type IIa and aggrecan, and an up
      regulation of HLA-DR, beginning at day 7 after induction. Interferon-gamma (INF
      gamma) is known to up-regulate HLA-DR. Therefore we measured INF-gamma levels in
      the supernatants of TGF-beta3-induced pellets and, indeed, INF-gamma was up
      regulated during chondrogenesis in ADSC pellet cultures. However, both
      undifferentiated and TGF-beta3-induced ADSC also showed expression of
      immunosuppressive HLA-G and interleukin (IL)-10 up-regulation. CONCLUSIONS: These
      results suggest that the immunogenicity of adult stem cell-derived tissue should
      be tested in animal models before clinical trials for allogeneic engineered
      tissue are considered.

PMID- 20795758
TI  - Clinical-grade, large-scale, feeder-free expansion of highly active human natural
      killer cells for adoptive immunotherapy using an automated bioreactor.
AB  - BACKGROUND AIMS: Natural killer (NK) cell-based adoptive immunotherapy is a
      promising approach for the treatment of cancer. Ex vivo expansion and activation
      of NK cells under good manufacturing practice (GMP) conditions are crucial for
      facilitating large clinical trials. The goal of this study was to optimize a
      large-scale, feeder-free, closed system for efficient NK cell expansion. METHODS:
      Peripheral blood mononuclear cells (PBMCs) from healthy donors and myeloma
      patients were cultured for 21 days using flasks, cell culture bags and
      bioreactors. Final products from different expansions were evaluated
      comparatively for phenotype and functionality. RESULTS: Significant NK cell
      expansions were obtained in all systems. The bioreactor yielded a final product
      rich in NK cells (mean 38%) ensuring that a clinically relevant cell dose was
      reached (mean 9.8 x 109 NK cells). Moreover, we observed that NK cells expanded
      in the bioreactor displayed significantly higher cytotoxic capacity. It was
      possible to attribute this partially to a higher expression level of NKp44
      compared with NK cells expanded in flasks. CONCLUSIONS: These results demonstrate
      that large amounts of highly active NK cells for adoptive immunotherapy can be
      produced in a closed, automated, large-scale bioreactor under feeder-free current
      GMP conditions, facilitating clinical trials for the use of these cells.

PMID- 20795759
TI  - Prolonged hypoxic culture and trypsinization increase the pro-angiogenic
      potential of human adipose tissue-derived stem cells.
AB  - BACKGROUND AIMS: Transplantation of mesenchymal stromal cells (MSC), including
      adipose tissue-derived stem cells (ASC), is a promising option in the treatment
      of vascular disease. Short-term hypoxic culture of MSC augments secretion of anti
      apoptotic and angiogenic cytokines. We hypothesized that prolonged hypoxic (1%
      and 5% oxygen) culture and trypsinization would augment ASC expression of anti
      apoptotic and angiogenic cytokines and increase the angiogenic potential of ASC
      conditioned media. METHODS: The effects of prolonged hypoxic culture on growth
      and pro-angiogenic properties were investigated using human ASC cultured at 1%,
      5% and 21% oxygen. The effect of trypsinization on the expression of pro
      angiogenic genes was also determined. RESULTS: Trypsinization induced up
      regulation of the vascular endothelial growth factor (VEGF) and insulin-like
      growth factor-1 (IGF-1) genes independent of oxygen concentration. The expression
      of VEGF and IGF-1 was up-regulated in ASC cultured at 1% oxygen for 13 days
      compared with 4 days. The VEGF concentration in ASC-conditioned media was higher
      after prolonged hypoxic culture compared with short-term culture, while the IGF-1
      and chemokine (CXC motif) ligand 12 (CXCL12) concentrations were unchanged. The
      VEGF receptor blocker SU5416 abolished angiogenesis in a cultured rat aortic ring
      model. Media from cells exposed to hypoxia increased angiogenesis, an effect that
      was dependent on factors other than just the VEGF concentration in the added
      media. CONCLUSIONS: Optimization of the angiogenic potential of stem cell-based
      therapy in the treatment of vascular disease is important. We have demonstrated
      that prolonged hypoxic culture and trypsinization augment the therapeutic
      angiogenic potential of ASC.

PMID- 20795760
TI  - Shipping of therapeutic somatic cell products.
AB  - BACKGROUND AIMS: Shipment of therapeutic somatic cells between a current good
      manufacturing practice (cGMP) facility and a clinic or between different cGMP
      facilities requires validated standard operating procedures (SOP). Under National
      Heart Lung & Blood Institute (NHLBI) sponsorship, the Production Assistance for
      Cellular Therapies (PACT) group conducted a validation study for the shipping SOP
      it has created, including shipments of cryopreserved somatic cells, fresh
      peripheral blood specimens and apheresis products. METHODS: Comparisons of pre-
      and post-shipped cells and cell products at the three participating facilities
      included measurements of viability, phenotypic profiles and cellular functions.
      The data were analyzed at the University of Pittsburgh Biostatistics Facility.
      RESULTS: No consistent shipping effects on cell viability, phenotype or functions
      were detected for cryopreserved and shipped peripheral blood mononuclear cells
      (PBMC), monocytes, immature dendritic cells (iDC), NK-92 or cytotoxic T cells
      (CTL). Cryopreserved mesenchymal stromal cells (MSC) had a significantly
      decreased viability after shipment, but this effect was in part because of inter
      laboratory variability in the viable cell counts. Shipments of fresh peripheral
      blood and apheresis products for the generation of CTL and dendritic cells (DC),
      respectively, had no significant effects on cell product quality. MSC were
      successfully generated from fresh bone marrow samples shipped overnight.
      CONCLUSIONS: This validation study provides a useful set of data for guiding
      shipments of therapeutic somatic cells in multi-institutional clinical trials.

PMID- 20795761
TI  - Invasive aspergillosis in acute leukemias: old and new risk factors and
      epidemiological trends.
AB  - In recent years, there has been increased interest in the development of
      prophylactic and diagnostic tools for patients at high risk for invasive
      aspergillosis (IA), resulting in a significant investment of human, technical,
      and economic resources. There are several classic risk factors for the
      development of IA, including neutropenia, graft-versus-host disease, and
      corticosteroid use. However, despite having similar risk profiles, only a subset
      of at-risk individuals will develop this fungal complication. At present, there
      is a significant expansion of the classically defined 'high-risk' group due to
      the ageing of the general population, the intensification of treatment
      strategies, and the introduction of new drugs into clinical practice (e.g.,
      monoclonal antibodies, TNF inhibitors). Therefore, an improved categorization of
      patients would be useful in order to better target available resources and avoid
      the risk of potential overtreatment and toxicities.

PMID- 20795762
TI  - Assessment of Candida species colonization and denture-related stomatitis in
      complete denture wearers.
AB  - Candida species are considered the primary causative agents of denture
      stomatitis, but their role in colonization and disease in denture wearers remains
      undefined. In this study, we investigated risk factors associated with
      progression to Candida-related denture stomatitis in patients using complete
      dentures, and we genetically identified Candida isolates associated with disease
      and colonization. We recruited 114 retirement home residents for this study, from
      whom oral mucosa samples were collected and cultured following oral cavity exams.
      Morphologic analysis was used to identify potential yeast-positive cultures,
      which were then characterized further by RFLP analysis. C. albicans was the most
      frequently recovered species (61; 41.5%), followed by C. glabrata (27; 18.4%),
      and C. tropicalis (19; 12.9%). In addition, 16 isolates (10.9%) of C.
      dubliniensis were recovered, which was the first identification of this species
      in clinical samples from Iran. This study demonstrated a significant association
      between the duration of denture wear and oral candidiasis. Furthermore, we noted
      a high prevalence of C. dubliniensis in complete denture wearers.

PMID- 20795763
TI  - Platelets enhance activity of antimycotic substances against non-Aspergillus
      fumigatus Aspergillus species in vitro.
AB  - Platelets are known to be part of haemostasis but they are also players in innate
      host defense. Recently, we observed that platelets attenuate the virulence of
      Aspergillus spp. in vitro. However, little is known about the antifungal effects
      of platelets in the presence of antimycotics against non-A. fumigatus Aspergillus
      species. We therefore investigated whether platelets increase the in vitro
      activity of amphotericin B, voriconazole, posaconazole and caspofungin against
      two clinical isolates each of Aspergillus flavus, Aspergillus terreus and
      Aspergillus niger. The antifungal activity was evaluated by assessing germination
      percentages, hyphal elongation and hyphal damage by use of XTT. The combination
      of platelets plus amphotericin B significantly (P < 0.05) enhanced the reduction
      of germination percentage compared to either substance alone. Among triazoles,
      voriconazole exhibited significant effects with platelets for all tested
      aspergilli. Overall, these findings suggest that among the tested antimycotic
      substances, amphotericin B in combination with platelets has enhancing effects in
      reducing germination and hyphal elongation in the tested non-A. fumigatus
      Aspergillus species. These data indicate that platelets act beneficially with
      antimycotics in an early stage of fungal growth by blocking and/or delaying
      fungal germination and hyphal elongation; both crucial mechanisms in the
      development of invasive fungal disease.

PMID- 20795764
TI  - In vitro susceptibility of Prototheca zopfii genotypes 1 and 2.
AB  - Prototheca zopfii causes bovine mastitis that leads to reduced milk production.
      Since P. zopfii isolates from mastitis have been assigned P. zopfii genotype 2,
      it suggests that this genotype is the etiologic agent of the infection. However,
      isolates of P. zopfii have not been investigated with regard to their in vitro
      drug susceptibility. In this study, we examine the susceptibility of genotype 2
      strains from bovine mastitis and genotype 1 isolates recovered from cow-barn
      surroundings. The in vitro susceptibility of ten isolates and the type strain
      (SAG2063(T)) of P. zopfii genotype 1, and equal number of genotype 2 isolates and
      the type strain (SAG2021(T)) were assessed by E-test against amphotericin B
      (AMB), gentamicin (GM), kanamycin (KM) and itraconazole (ITZ). Results showed
      that P. zopfii genotype 1 isolates are more susceptible in vitro to AMB, GM and
      KM than those of genotype 2. Moreover, genotype 2 isolates and seven isolates of
      genotype 1, including the type strain, are not susceptible to ITZ (>10 MUg/ml).
      Thus, drug susceptibility of P. zopfii differs between these two genotypes.

PMID- 20795765
TI  - Acquired antifungal drug resistance in Aspergillus fumigatus: epidemiology and
      detection.
AB  - Voriconazole is the recommended agent for invasive aspergillosis, with lipid
      amphotericin B or caspofungin as second line treatment choices. Being the only
      agents available in oral formulation, azoles are used in chronic infections and
      often over longer time periods. In addition to being used in clinical medicine,
      azoles are employed extensively in agriculture. Azole-resistant Aspergillus has
      been isolated in azole naive patients, in azole exposed patients and in the
      environment. The primary underlying mechanism of resistance is as a result of
      alterations in the cyp51A target gene, with a variety of mutations found in
      clinical isolates but just one identified in a environmental strain (a point
      mutation at codon 98 accompanied by a tandem repeat in the promoter region). Much
      less is currently known about echinocandin resistance in Aspergillus, in part
      because susceptibility testing is not routinely performed and because the methods
      suffer from technical difficulties and suboptimal reproducibility. Clinical
      breakthrough cases have been reported however, and resistance has been confirmed
      in vivo. In this paper we review the current knowledge on epidemiology,
      susceptibility testing and underlying mechanisms involved in azole and
      echinocandin resistance in Aspergillus.

PMID- 20795766
TI  - Novel diagnostics: progress toward a breath test for invasive Aspergillus
      fumigatus.
AB  - In this paper we will briefly review some of the possible techniques for the
      development of a breath test for aspergillosis and describe progress made toward
      validating 2-Pentyl furan (2PF) as a marker of Aspergillus infection. Breath
      testing to diagnose pulmonary aspergillosis is attractive because of the
      proximity of the lesion to the sample and the simplicity of obtaining diagnostic
      specimens. Techniques to detect volatile organic compounds (VOCs) in breath
      discussed include the electronic nose, selective ion flow mass spectrometry
      (SIFT), ion mobility spectrometry (IMS) and gas chromatography with mass
      spectrometry (GC/MS). We have used GC/MS to identify Aspergillus-derived VOC's in
      the head space of cultures. A promising diagnostic marker molecule is 2PF, which
      was not detectable from cultures of bacterial respiratory pathogens with the
      possible exception of Streptococcus pneumoniae. 2-Pentylfuran is not known to be
      produced by mammalian metabolism and was not detectable in the breath of healthy
      controls, or neutropenic subjects. In contrast, 2PF was found in the breath of
      patients with lung disease who were colonized or infected with A. fumigatus. Case
      reports are presented of two severely immune compromised patients with invasive
      aspergillosis from whom 2PF was detected in multiple breath samples but became
      undetectable with effective treatment. A well conducted prospective trial is
      needed to validate the clinical usefulness of this marker for diagnosis and
      monitoring of invasive aspergillosis. Unanswered questions remaining include how
      much 2PF, if any, is produced by extensive lung inflammation, and whether food
      containing high levels of 2PF can cause false positive breath tests either from
      contamination in the mouth or gastrointestinal absorption and subsequent
      excretion in the breath.

PMID- 20795767
TI  - Radiotracers for fungal infection imaging.
AB  - Invasive fungal infections are recognized as an important cause of morbidity and
      mortality in the immunocompromised host. Rapid initiation of adequate antifungal
      treatment is often hampered by the limitations of current diagnostic methods.
      This review encompasses the promises and limitations of newer tracers (believed
      to target the infectious agents), i.e., radiolabeled antimicrobial peptides,
      antifungals and chitin-specific agents, for fungal infection imaging by
      scintigraphy. In mice (99m)Tc-labeled peptides derived from human ubiquicidin
      (UBI29-41) and lactoferrin (hLF1-11) distinguished local Candida albicans and
      Aspergillus fumigatus infections from sterile inflammatory processes, but not
      from bacterial infections. Clinical trials showed that (99m)Tc-UBI29-41 can
      distinguish infections from inflammatory lesions with 80% specificity and 100%
      sensitivity. (99m)Tc-hLF1-11 was able to monitor the antifungal effects of
      fluconazole on C. albicans infections. Moreover, (99m)Tc-fluconazole proved to be
      an excellent tracer for C. albicans infections as it did not accumulate in
      bacterial infections and inflammatory processes. However this tracer poorly
      detected A. fumigatus infections. Furthermore, (123)I-chitinase and (99m)Tc-HYNIC
      CBP21 accumulated in both C. albicans and A. fumigatus infections in mice at
      later time points. In conclusion, despite the recent advances in radiolabeled
      imaging techniques for invasive fungal infections, the search for better tracers
      for fungal infection imaging should be continued.

PMID- 20795768
TI  - Frequency of pulmonary hypertension in asymptomatic beta-thalassemia major
      patients and the role of physiological parameters in evaluation.
AB  - In this study, the authors aimed to evaluate the frequency of pulmonary
      hypertension (PHT) in asymptomatic thalassemia major (TM) patients, and to
      investigate the impact of pulmonary function test (PFT) and CO diffusion results
      on the evaluation of pulmonary hypertension. Data from 50 asymptomatic patients
      with TM over age 10 were evaluated. Pulmonary hypertension was diagnosed in 10
      patients (20%). High tricuspid regurgitant jet velocity was found in 14% of
      adults and in 25% of children. Pulmonary function test including CO diffusion
      testing results were not different between the TM patients with or without
      pulmonary hypertension. In conclusion, PHT was frequent among TM patients even
      they were asymptomatic and although PFT results has shown lack of association, it
      should be investigated in larger population.

PMID- 20795769
TI  - Comparison of doxorubicin cardiotoxicity in pediatric sarcoma patients when given
      with dexrazoxane versus as continuous infusion.
AB  - Doxorubicin is an effective agent for many malignancies. To limit cardiotoxicity,
      doxorubicin can be given as prolonged infusion (PIDX) or bolus infusion following
      dexrazoxane (DZX). The authors report their institutional experience comparing
      PIDX and DZX in a sarcoma cohort. Retrospective record review for newly diagnosed
      sarcoma patients at the University of Texas M.D. Anderson Cancer Center from June
      1998 to June 2006. There were 23 Ewing's sarcoma (EWS) patients treated with DZX
      and 40 osteosarcoma (OS) patients treated with PIDX. The DZX group had higher
      mean cumulative anthracycline dose (510 mg/m(2) [SD 120 mg/m(2)] versus 414
      mg/m(2) [SD 99 mg/m(2)], P = .002), however mean lowest left ventricular ejection
      fraction (EF) values were higher for DZX (52.5% [SD 5.6%] versus 47.2% [SD
      10.9%], P = .014). Fifteen of 19 patients with cardiac dysfunction were PIDX
      patients (P = .15). Five PIDX patients required cardiac medication, and 1 patient
      died of congestive heart failure (CHF). Sixteen patients with cardiac dysfunction
      had improvement, demonstrated by EF >= 50% at last echocardiogram. Although not
      statistically significant, there were 4 DZX patients with cardiac dysfunction.
      Prospective studies are required to determine which strategy has long-term
      advantages and if certain patients are at increased risk for cardiac dysfunction.

PMID- 20795770
TI  - Causes for hospitalization and death in Iranian patients with beta-thalassemia
      major.
AB  - There are limited studies that have focused on the causes for hospitalization as
      an indicator of morbidity in patients with beta-thalassemia major (BTM). A cross
      sectional study was conducted to determine the main causes for hospitalization
      and death in hospitalized BTM patients in a referral hospital in Shiraz, southern
      Iran. During a 5-year period, 555 BTM patients were admitted to the hospital, of
      which 390 (67.7%) were 10 to 20 years of age. The most frequent causes for
      hospitalization were splenectomy (23%), heart failure (22.6%), liver biopsy
      (22.2%), uncontrolled diabetes (10.9%), arrhythmia (7.2%), cholecystectomy
      (3.8%), hypoparathyroidism (2.1%), and sepsis (2%). Of the hospitalized patients,
      65 (11%), with a mean age of 16.1 +/- 4.2 years, died. The most common causes of
      death were cardiomyopathy (72.3%), infections (17%), malignancies (3.1%), and
      cerebrovascular accidents (3.1%). Survival of our patients was less than in
      developed countries and cardiac complications were the most common cause of
      mortality and morbidity in these patients. Regarding the key role of iron
      chelation in prevention of different complications in BTM, correction of iron
      chelation regimen should be well considered.

PMID- 20795771
TI  - Language skills in a child with Leber hereditary optic neuropathy following
      intrathecal chemotherapy for acute lymphoblastic leukemia.
AB  - The language skills of a male child with Leber hereditary optic neuropathy (LHON)
      and coincidentally treated for acute lymphoblastic leukemia (ALL) with
      intrathecal chemotherapy at the age of 3 years 8 months were comprehensively
      evaluated twice over a 6-month period approximately 5&#x00BD; years after
      diagnosis of ALL. Despite marked chemotherapy-related leukoencephalopathic
      changes documented on magnetic resonance imaging, the child presented with stable
      language skills, which were generally average to above-average based on the
      normative data from a comprehensive language test battery. In light of the
      coincidental presentation in the child of a diagnosis of LHON, which may lead to
      serious vision impairment and increased vulnerability to drug neurotoxicity,
      coupled with a history of central nervous system (CNS)-directed treatment for ALL
      resulting in progressive white matter pathology, the study highlights the
      importance of ongoing monitoring of the child's language development throughout
      his adolescent years.

PMID- 20795772
TI  - Neonatal purpura fulminans secondary to group B streptococcal infection.
AB  - Purpura fulminans is an acute and frequently fatal disorder characterized by
      sudden onset of progressive cutaneous hemorrhage and necrosis due to dermal
      vascular thrombosis and disseminated intravascular coagulation. The authors
      present a neonate with extensive purpura fulminans due to group B streptoccoccal
      septicemia and evaluated the attributable clinical mortality and morbidity of
      this potentially lethal syndrome. Clinicians especially neonatologists should be
      aware that early-onset sepsis of group B Streptococcus in the newborn infant with
      purpura fulminans could be a cause of maternal carriage due to colonization of
      this pathogen microorganism.

PMID- 20795773
TI  - Premarital screening test results for beta-thalassemia and sickle cell anemia
      trait in east Mediterranean region of Turkey.
AB  - Hemoglobinopathies are common diseases in Mediterranean region of Turkey. In this
      study, the results of a 3-year premarital screening program are reported in
      Kahramanmaras province, which is located in East Mediterranean region. A total of
      48,126 persons were screened in this program. Hematological analyses and
      electrophoresis were done to identify carriers. The prevalence of beta
      thalassemia trait and of sickle cell anemia trait, which were 2.1% and 0.5% in
      Turkey, were found to be 2.8% and 0.4%, respectively, in our study. Of the
      carriers of the beta-thalassemia trait, 82% had high hemoglobin A2, 34% had high
      hemoglobin F, and 18% had both high hemoglobin F and hemoglobin A2. beta
      Thalassemia trait in Kahramanmaras is slightly higher than the average rate in
      Turkey. However, sickle cell anemia trait is similar to Turkey's averages.

PMID- 20795774
TI  - Mutation of the proton-coupled folate transporter gene (PCFT-SLC46A1) in Turkish
      siblings with hereditary folate malabsorption.
AB  - Hereditary folate malabsorption (HFM) is a rare autosomal recessive disorder
      characterized by systemic and central nervous system folate deficiency. Turkish
      siblings are reported with the clinical syndrome of HFM, homozygous for deletion
      of 2 bases (c.204_205 delCC) within the first exon of the proton-coupled folate
      transporter (PCFT) gene, causing a frameshift. Low blood and cerebrospinal fluid
      folate levels were detected at ages 3.5 and 1 month. Treatment with parenteral 5
      formyltetrahydrofolate resulted in normal development now at ages 3 and 1 year.
      Extending current knowledge on the phenotypic manifestations of HFM and the PCFT
      mutation spectrum will provide opportunities to define possible genotype
      phenotype correlations and clarify the basis for the phenotypic variability that
      is characteristic of this disorder.

PMID- 20795775
TI  - Effects of gluten and emulsifier on some properties of eriste prepared with
      legume flours.
AB  - In the present study, eriste was produced from 70% coarse and fine flours of
      common bean/lentil+30% wheat semolina (WS) with the addition of gluten (0%, 2.5%
      and 5%) and sodium stearoyl 2-lactylate (SSL) (0% and 0.6%). Chemical,
      nutritional, and sensory properties and cooking quality of eriste samples were
      investigated. As coarse common bean flour (CCF) and coarse lentil flour (CLF)
      have higher rates for ash and protein, these parameters were also found higher in
      the end products prepared from CCF and CLF than those prepared from fine common
      bean flour (FCF) and fine lentil flour (FLF). Protein contents and in vitro
      protein digestibility values of eriste containing common bean flours increased
      with gluten addition while ash values decreased in the samples containing 5%
      gluten. SSL addition did not alter the chemical properties, but it increased
      brightness and decreased redness values of samples produced from CCF and CLF.
      Generally SSL addition increased weight and volume increase values of eriste
      samples made with all legume flours. According to the sensory analysis results,
      gluten addition improved the surface smoothness and appearance in samples made
      with CCF, FLF and CLF. Samples made from CCF and CLF were preferred to samples
      made from FCF and FLF with respect to taste, odor and stickiness.

PMID- 20795776
TI  - The complete mitochondrial genome of the raccoon dog.

PMID- 20795777
TI  - Complete mitochondrial genome of the Korean goral Naemorhaedus caudatus
      (Ruminantia, Bovidae, Antilopinae) and conserved domains in the control region of
      Caprini.
AB  - In the present paper, we describe the complete mitochondrial genome of the Korean
      goral Naemorhaedus caudatus with particular emphasis on the control region (CR).
      The mitochondrial genome of M. moschiferus was 16,519 bp in size with mostly
      conserved structures (e.g. 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes
      and 1 CR). Its general characteristics were shown and discussed.

PMID- 20795778
TI  - Mitochondrial genome of the Korean musk deer Moschus moschiferus (Artiodactyla,
      Ruminantia, Moschidae).
AB  - The complete mitochondrial genome sequence of the Korean musk deer Moschus
      moschiferus, which is an endangered species in Korea. The circle genome (16,351
      bp in size) consists of 13 protein-coding, 22 tRNA, and 2 rRNA genes, and 1
      control region (CR), as found in other metazoan animals. The CR was located
      between the tRNA(Pro) and tRNA(Phe) genes and is 923 bp in length. The typical
      conserved domains such as ETAS1 and 2, CSB1 and 2, and TAS were identified in the
      CR of M. moschiferus.

PMID- 20795779
TI  - The mitochondrial genome of the Japanese skeleton shrimp Caprella mutica
      (Amphipoda: Caprellidea) reveals a unique gene order and shared apomorphic
      translocations with Gammaridea.
AB  - This study presents the complete mitochondrial (mt) genome of the amphipod
      Caprella mutica, an east-Asian species, which recently invaded the coastal
      regions of North America, Europe, and New Zealand. It is the first complete
      sequence of a member of the amphipod subclade Caprellidea. The mt genome has a
      total length of 15,427 bp and is organized in a circular double-strand molecule.
      All 37 mt genes are present, including the common set of 22 tRNAs. Particularly
      noticeable is the duplication of the control region (CR). The additional CR is
      located between nad6 and cob, and is almost identical to the original one. The
      most extensive changes in the gene order affect nad5 and a block consisting of
      trnH, nad4, nad4L, and trnP-all inserted near the original CR. The gene nad5 is
      also inverted. Furthermore, a comparison with the pancrustacean ground pattern
      reveals additional changes of individual tRNA genes. Some of these changes are
      also shared by Metacrangonyx longipes and Parhyale hawaiensis. These arrangements
      were found only in amphipods and might be considered as apomorphic by character
      states of Amphipoda. In all the three species, there is good evidence that trnG
      originated from a rare duplication/remolding event of the adjacent trnW gene.
      Nevertheless, each of the three available amphipod mitogenome sequences also
      bears unique rearrangements. C. mutica, however, shows the most extensive
      rearrangement in comparison with the pancrustacean ground pattern.

PMID- 20795780
TI  - Mitochondrial genomics in Orthoptera using MOSAS.
AB  - We present complete mitochondrial genomes (mitogenomes) for three orthopterans
      (Xyleus modestus, Physemacris variolosa, and Ellipes minuta) and describe MOSAS
      (manipulation, organization, storage, and analysis of sequences), software we
      developed to facilitate annotation and analysis. We analyze the base composition,
      start and stop codons, non-coding regions, and gene order among these and 18
      other orthopteran mitogenomes from GenBank and reconstruct a phylogeny of
      Orthoptera. We propose a tetranucleotide start codon for cox1, and hypothesize
      that the tRNA(Asp)-tRNA(Lys) rearrangement is a synapomorphy for Acridomorpha,
      but not Caelifera. We further describe MOSAS, user-friendly software we used for
      this analysis. MOSAS streamlines sequence data storage, organization, annotation,
      and alignment, and provides convenient search tools for dataset construction and
      a robust annotation engine particularly suited to annotating mitogenomes
      (available at http://mosas.byu.edu).

PMID- 20795781
TI  - Mitochondrial genome phylogeny among Asiatic black bear Ursus thibetanus
      subspecies and comprehensive analysis of their control regions.
AB  - The complete mitochondrial genome (16,824 bp) of an Asiatic black bear Ursus
      thibetanus ussuricus (Mammalia, Carnivora, Ursidae) was newly sequenced and
      characterized in detail. It is the second mitochondrial genome from this
      subspecies which has been completely sequenced. The two U. t. ussuricus
      individuals were compared with each other and then with individuals from the
      other four U. thibetanus subspecies and the other nine ursid species, focusing
      especially on the control regions in the 14 mitochondrial genomes. Within these
      control regions, tandem repeats of basically 10 bp (5'-ACGCACGTGT-3' or its
      derivatives) were found in Domain II. Plausible secondary structures of the
      repeat region were compared between the North and South Korean individuals of U.
      t. ussuricus. According to the maximum likelihood and Bayesian inference trees
      inferred from the nucleotide sequences of 13 protein-coding and two rRNA genes,
      the ursine members within the monophyletic ursid clade can be divided into at
      least three groups: A, B, and C. According to this analysis, U. thibetanus
      subspecies were found with Ursus americanus and Ursus malayanus within Group A,
      showing the following relationships with nodal bootstrap values above 91% and
      Bayesian posterior probabilities of 1.00: ([(U. t. thibetanus, U. t. formosanus),
      U. t. spp.], U. t. ussuricus), U. t. mupinensis. In addition, we present a
      hypothetical scenario of the evolution of the major repeat motifs in the control
      region.

PMID- 20795782
TI  - DNA barcoding on subsets of three families in Aves.
AB  - BACKGROUND AND AIMS: Previous studies carried out with DNA barcoding, based on
      regional groups, have shown that a standard mitochondrial gene could be used to
      identify birds. In the present study, we present an additional DNA barcoding
      survey of birds, using taxonomic groups instead of regional groups to verify the
      effectiveness of DNA barcoding on distinguishing species and to test whether the
      intraspecific clusters of species are associated with geographical
      discontinuities. MATERIALS AND METHODS: Taxonomic groups of three avian families-
      Phasianidae, Accipitridae, and Strigidae--were included in the study. The
      cytochrome c oxidase I (COI) sequences of 49 individuals were determined.
      Together with 122 sequences from previous studies, a total of 171 sequences from
      66 bird species were analyzed. RESULTS AND CONCLUSION: Results showed that all 66
      species investigated had unique COI sequences and no sequences were shared
      between the species. Our results were congruent with previous studies suggesting
      that the COI barcode permits distinguishing most of the closely related species.
      Furthermore, by using geographically distinct clusters, diagnostic characters,
      and threshold levels, deep genetic splits (>1.5%) were observed in three species,
      and we therefore suggest treating them as evolutionary significant units.

PMID- 20795783
TI  - Improved characterisation of among-lineage rate variation in cetacean mitogenomes
      using codon-partitioned relaxed clocks.
AB  - BACKGROUND AND AIMS: There is extensive variation in substitution rates among
      metazoan mitochondrial genomes, including differences among lineages and among
      sites. Differences in substitution rates among lineages are routinely taken into
      account in molecular phylogenetic and dating analyses. However, this is rarely
      the case for differences in the lineage-specific patterns of rate variation among
      sites. MATERIALS AND METHODS: We analysed an alignment of 32 cetacean mitogenomes
      using a partitioned relaxed-clock approach, in which a separate relaxed-clock
      model was applied to each of the three codon positions of the protein-coding
      genes. RESULTS: By comparing Bayes factors, we found overwhelming support for
      this model compared with a strict-clock model and less-complex models comprising
      fewer relaxed clocks. Our analyses reveal the presence of substantial rate
      heterogeneity among cetacean lineages, and that these patterns of variation
      differ between codon positions. However, we find no evidence of mitochondrial
      rate autocorrelation throughout the cetacean phylogeny. CONCLUSIONS: Our study
      confirms the feasibility of applying a partitioned relaxed-clock model to
      mitogenomic data, and suggests that molecular phylogenetic and dating analyses
      may be improved by the application of these models.

PMID- 20795784
TI  - Chemical composition and antibacterial activity of essential oils of
      Tripleurospermum disciforme in three developmental stages.
AB  - CONTEXT: Tripleurospermum disciforme (C.A. Mey) Schultz Bip. (Asteraceae) is a
      widespread biennial species which also has traditional medicinal uses. According
      to the few recent studies, essential oils of this species exhibit anti
      inflammatory, antispasmodic, antiseptic, antifungal, antiulcer, and antioxidant
      activity. OBJECTIVE: The chemical compositions of the hydrodistilled oils of T.
      disciforme of Iranian origin are studied in the stages of prior to flowering,
      flowering, and post flowering, for the first time. Also, we investigated the
      antibacterial activities of the oils. MATERIALS AND METHODS: The essential oils
      of air-dried T. disciforme were obtained by hydrodistillation in three different
      developmental stages and analyzed by gas chromatography-mass spectrometry (GC
      MS). The antimicrobial activity of the isolated essential oil, in the three
      stages, was also investigated against four Gram-positive and four Gram-negative
      bacteria. RESULTS: Twenty-one components were identified in the essential oils of
      T. disciforme, and the highest amount of oil was extracted at the flowering
      stage. The main component of the species in the flowering stage was beta
      farnesene (22.46%) and the other major components were beta-sesquiphellandrene
      (17.85%), p-methoxy-beta-cyclopropylstyrene (16.64%), heptadecane (10.6%), p
      methoxy-humulene oxide (6.88%) and benzene acetaldehyde (9.3%). The MIC of
      essential oil was evaluated from 4 uL ml(-1) against Staphylococcus subtilis and
      Bacillus cereus to 22 uL ml(-1) against Citrobacter amalonaticus. DISCUSSION AND
      CONCLUSION: This study demonstrates the occurrence of beta-farnesene/beta
      sesquiphellandrene chemotype of T. disciforme in western regions of Iran that are
      different from previous reports. The findings also showed that the essential oils
      T. disciforme have excellent antibacterial activities and thus have great
      potentiality to be used as a resource for natural health products.

PMID- 20795785
TI  - Effects of human recombinant-interferon beta in experimental autoimmune
      encephalomyelitis in guinea pigs.
AB  - CONTEXT: Although clinical data for beneficial effects of Betaferon, human
      recombinant-interferon (r-IFN) beta-1b, are accumulating, what is less evident is
      how and why it works. OBJECTIVE: The present study was carried out to examine
      whether Betaferon suppresses progression of experimental autoimmune
      encephalomyelitis (EAE). MATERIALS AND METHODS: The EAE model was employed in
      guinea pigs in vivo, and mononuclear cell proliferation and 2',5'-oligoadenylate
      synthetase activity were assessed in vitro. RESULTS: Betaferon was more reactive
      in two assays of guinea pigs, mitogen-induced proliferation of peripheral blood
      mononuclear cells and 2',5'-oligoadenylate synthetase activity of blood, than in
      rats and rabbits. Guinea pigs were immunized actively by antigen, porcine myelin
      basic protein. The neurological deficits were assessed by clinical signs scored
      daily. Guinea pig Betaferon, replaced with guinea pig albumin (GPA), at 1.2 and
      12.0 MIU/kg/day or vehicle was administered subcutaneously daily for 20 days in
      the immunized guinea pigs. GPA-Betaferon suppressed the manifestation of ataxia
      or more progression of chronic neurological deficits significantly at 1.2 MIU/kg
      (p <0.05). Two out of 10 animals manifested no clinical signs in the GPA
      Betaferon-treated group with the higher dose, while all animals were worsened
      with typical clinical signs of EAE in the vehicle group where mononuclear cell
      infiltrates around blood vessels were seen in the spinal cord of vehicle-treated
      animals. DISCUSSION AND CONCLUSION: Human r-IFN beta-1b attenuates progression of
      neurological deficits in the EAE model of guinea pigs with evidence for higher
      susceptibility of animal cells/tissues to the human cytokine, in contrast with
      rodents and rabbits.

PMID- 20795786
TI  - Enteric-coated mycophenolate sodium.
AB  - IMPORTANCE OF THE FIELD: Mycophenolic acid (MPA) therapy is a fundamental
      component of most post-transplant immunosuppressive regimens. Side effects,
      however, are common and frequently necessitate dose reductions or
      discontinuations. AREAS COVERED IN THIS REVIEW: Enteric-coated mycophenolate
      sodium (EC-MPS) is designed to improve the gastrointestinal (GI) tolerability of
      MPA. This review assesses the pharmacology, efficacy and safety of EC-MPS. WHAT
      THE READER WILL GAIN: An understanding of the use of EC-MPS in solid organ
      transplantation and the key trials examining the GI impact of EC-MPS versus the
      immediate-release mycophenolate mofetil (MMF) formulation. The article also
      addresses the possible impact of proton pump inhibitor therapy, and the optimal
      MPA dose with different concomitant immunosuppressants. TAKE HOME MESSAGE:
      Evidence from blinded trials using standard reporting measures or patient
      reported outcomes has not confirmed a significant improvement in the GI symptom
      burden using EC-MPS. Several open-label studies, however, have consistently shown
      an improvement in GI tolerability with EC-MPS, which can permit restoration of
      the optimal MPA dose. EC-MPS has equal efficacy and possibly a different
      tolerability profile to MMF, thus offering a choice to physicians and their
      patients, particularly those experiencing MMF-related GI symptoms, diabetic
      patients or those in whom an MPA dose reduction is required.

PMID- 20795787
TI  - Review of clinical trials conducted in Waldenstrom macroglobulinemia and
      recommendations for reporting clinical trial responses in these patients.
AB  - Many novel therapeutic agents are being tested in clinical trials for Waldenstrom
      macroglobulinemia (WM). However, given the paucity of large clinical trials in
      WM, the establishment of a standard treatment regimen that can be used for
      comparison of response has become challenging. We therefore performed a review of
      published clinical trials in WM. Systematic searches of the PubMed and Medline
      databases, including The Cochrane Library, were performed for the search terms:
      clinical trials, Waldenstrom, macroglobulinemia, and lymphoplasmacytic lymphoma.
      Studies of transplant in WM are beyond the scope of this review and were
      excluded. A total of 44 clinical trials were found in this search (38 full
      articles, six abstracts). Of these, 11 were performed in patients with untreated
      WM, 14 in patients with relapsed or refractory WM, 17 in both upfront and
      relapsed or refractory WM, and two studies did not provide this information.
      Based on this review, we recommend new response criteria and definitions of time
      to event analysis to be used in future clinical trials of WM. This review of the
      published literature would serve as a reference for comparison of response and
      survival analysis in current clinical trials.

PMID- 20795788
TI  - Targeting CD52 as a novel therapeutic strategy in angioimmunoblastic T-cell
      lymphoma.

PMID- 20795790
TI  - Prognostic implications of extranodal involvement in patients with diffuse large
      B-cell lymphoma treated with rituximab and cyclophosphamide, doxorubicin,
      vincristine, and prednisone.
AB  - The addition of rituximab (R) to standard CHOP (cyclophosphamide, doxorubicin,
      vincristine, and prednisone) chemotherapy has altered the significance of
      previously recognized prognostic factors. We sought to re-examine the prognostic
      utility of (1) the number of extranodal sites of disease involvement, and (2) a
      primary extranodal presentation in patients with DLBCL treated with
      immunochemotherapy. We retrospectively analyzed all patients with DLBCL diagnosed
      between January 1979 and May 2006 who were treated with an anthracycline-based
      therapy with curative intent. In all, 1781 patients were identified, of whom 513
      (29%) received R-CHOP. In the R-CHOP group, extranodal involvement as defined by
      the International Prognostic Index (>or=2 sites) was not prognostic on
      multivariate analysis, but the presence of any extranodal involvement (>or=1
      site) was associated with decreased progression-free survival (HR 1.6, 95% CI 1.1
      2.4, p = 0.024) and overall survival (HR 1.8, 95% CI 1.1-2.7, p = 0.011). A total
      of 133 (26%) R-CHOP treated patients presented with primary extranodal DLBCL.
      There was no difference in outcome between patients with primary extranodal and
      nodal DLBCL, and no primary site of involvement was associated with an inferior
      outcome. In patients with DLBCL treated with R-CHOP, the presence of extranodal
      disease remains prognostic, whereas a primary extranodal presentation did not
      affect outcome.

PMID- 20795791
TI  - Prokineticin-1/endocrine gland-derived vascular endothelial growth factor is a
      survival factor for human multiple myeloma cells.
AB  - Prokineticin-1 (PK1) has been identified as a mitogen-specific protein for the
      endothelium of steroidogenic glands. Here we report a novel function of PK1 in
      the regulation of multiple myeloma (MM) cells. PK1 activates multiple signals
      including mitogen-activated protein kinase (MAPK), PI3K-AKT, and Jak-STAT3,
      sphingosine kinase-1 (SPK1) in MM cells. Treatment of MM cells with PK1 causes a
      time- and dose-dependent phosphorylation of MAPK, AKT and STAT3 and upregulation
      of SPK1 expression and cellular activity. We also show that PK1 upregulates Mcl-1
      expression in a time- and dose-dependent manner in human MM cell lines and in the
      cells of patients with MM. Pertussis toxin, a pan-PK1 receptor inhibitor, can
      block PK1-induced upregulation of Mcl-1, indicating it relates to a G-protein
      coupled receptor. We also show that PK1 protects MM cells against apoptosis
      induced by starvation for fetal calf serum (FBS), or for FBS and IL-6. Taken
      together, PK1 activates multiple signaling pathways and, upregulates Mcl-1
      expression, leading to proliferation and survival of MM cells.

PMID- 20795789
TI  - Acute myeloid leukemia is characterized by Wnt pathway inhibitor promoter
      hypermethylation.
AB  - Nuclear localization of non-phosphorylated, active beta-catenin is a measure of
      Wnt pathway activation and is associated with adverse outcome in patients with
      acute myeloid leukemia (AML). While genetic alterations of the Wnt pathway are
      infrequent in AML, inhibitors of this pathway are silenced by promoter
      methylation in other malignanices. Leukemia cell lines were examined for Wnt
      pathway inhibitor methylation and total beta-catenin levels, and had frequent
      methylation of Wnt inhibitors and upregulated beta-catenin by Western blot and
      immunofluorescence. One hundred sixty-nine AML samples were examined for
      methylation of Wnt inhibitor genes. Diagnostic samples from 72 patients with
      normal cytogenetics who received standard high-dose induction chemotherapy were
      evaluated for associations between methylation and event-free or overall
      survival. Extensive methylation of Wnt pathway inhibitor genes was observed in
      cell lines, and 89% of primary AML samples had at least one methylated gene: DKK1
      (16%), DKK3 (8%), RUNX3 (27%), sFRP1 (34%), sFRP2 (66%), sFRP4 (9%), sFRP5 (54%),
      SOX17 (29%), and WIF1 (32%). In contrast to epithelial tumors, methylation of APC
      (2%) and RASSF1A (0%) was rare. In patients with AML with normal cytogenetics,
      sFRP2 and sFRP5 methylation at the time of diagnosis was associated with an
      increased risk of relapse, and sFRP2 methylation was associated with an increased
      risk for death. In patients with AML: (a) there is a high frequency of Wnt
      pathway inhibitor methylation; (b) Wnt pathway inhibitor methylation is distinct
      from that observed in epithelial malignancies; and (c) methylation of sFRP2 and
      sFRP5 may predict adverse clinical outcome in patients with normal karyotype AML.

PMID- 20795792
TI  - Clinical characteristics and resource utilization of patients with bipolar
      disorder who have frequent psychiatric interventions.
AB  - OBJECTIVE: To compare the demographics, clinical characteristics and resource
      utilization of patients with bipolar disorder who required frequent psychiatric
      interventions (FPIs) with those needing fewer interventions in the Duke
      Healthcare System database between 1999 and 2005. METHODS: This retrospective
      analysis was conducted using electronic medical records of bipolar patients with
      FPIs, defined as having >=4 clinically significant events (CSEs) in any 12-month
      period while in the Duke University Healthcare System. CSEs were composed of
      emergency room visits, inpatient hospitalizations, or a change in psychotropic
      medication due to psychiatric symptoms (score>=4 on the Clinical Global
      Impressions-Severity scale). Data were compared between patients with and without
      FPIs. RESULTS: Of 632 patients with bipolar disorder 52.5% were identified as
      having FPIs. These patients were younger and more often female and African
      American than those with fewer interventions (p<0.01 for all). Patients with FPIs
      were generally prescribed more psychotropic and non-psychotropic medications,
      utilized more healthcare resources and experienced more psychiatric co
      morbidities than those who did not require FPIs (p<0.01 for all). LIMITATIONS:
      These results are from a single healthcare system and may not be generalizable to
      all patients with bipolar disorder. This analysis was retrospective and relied on
      availability of adequate information recording and coding of diagnoses by
      physicians. CONCLUSIONS: Patients with bipolar disorder who required FPIs were
      significantly different from those with fewer clinically defined interventions
      with respect to their demographic and clinical characteristics and prescribed
      medications.

PMID- 20795793
TI  - Testosterone replacement therapy by testosterone ointment relieves lower urinary
      tract symptoms in late onset hypogonadism patients.
AB  - INTRODUCTION: Patients with late onset hypogonadism (LOH) also suffered from
      lower urinary tract symptoms (LUTS) and LOH symptoms. The objects of this study
      are to evaluate the efficacy of testosterone replace therapy (TRT) by
      testosterone ointment (Glowmin: GL) for LUTS in LOH patients. METHODS: The Aging
      Male Symptom (AMS) scale, Medical Outcomes Study (MOS) 36-Item Short-Form Health
      Survey (SF-36), International Index of Erectile Function (IIEF-5) and the
      International Prostate Symptom Score (IPSS) were obtained from patients with LOH.
      A total of 41 patients with LOH have been treated with TRT using 6 mg/day of GL
      for 3 months. Serum free testosterone levels (FT) and these four scores were
      compared before and after TRT. RESULTS: Serum FT levels and the scores for the
      four parameters of AMS, six of eight domains in SF-36, IIEF-5 and total IPSS
      improved significantly after 3 months TRT. In addition, all IPSS domains also
      improved significantly, and voiding disturbance seems to have improved more than
      storage disturbance (P = 0.0280 vs. 0.0483). CONCLUSION: TRT by administration of
      GL is considered to be effective in the improvement of not only ED and LOH
      symptoms, but also LUTS (especially voiding disturbance) of patients with LOH.

PMID- 20795794
TI  - Pharmacokinetic evaluation of fosaprepitant dimeglumine.
AB  - IMPORTANCE OF THE FIELD: Chemotherapy induced nausea and vomiting (CINV) is a
      common complication in the treatment of patients with cancer. The introduction of
      the first in class neurokinin-1 receptor antagonist aprepitant provided additive
      control on CINV in combination to existing antiemetics. Due to formulation
      issues, aprepitant is only available for oral administration. Fosaprepitant, a
      prodrug of aprepitant, was introduced to the market in 2008 as an intravenous
      bioequivalent to aprepitant. AREAS COVERED IN THIS REVIEW: This review examines
      the chemical development of fosaprepitant, its pharmacokinetic properties,
      approved uses and potential applications. WHAT THE READER WILL GAIN: The reader
      will get up-to-date information on the pharmacology and clinical uses of
      fosaprepitant. Clinical studies have demonstrated pharmacokinetic bioequivalence
      of aprepitant 125 mg to fosaprepitant 115 mg, as well as comparable efficacy in
      prevention of acute and delayed emesis following the first day of chemotherapy
      regimens. TAKE HOME MESSAGE: Fosaprepitant is an intravenous prodrug of
      aprepitant that offers a new alternative to patients with CINV. Currently,
      fosaprepitant can substitute oral aprepitant in day 1 of a 3-day regimen. Current
      studies show that a single-day fosaprepitant regimen is also bioequivalent to the
      3-day aprepitant regimen; this could significantly simplify the care for CINV
      patients in the future.

PMID- 20795796
TI  - Development and psychometric testing of a trans-professional evidence-based
      practice profile questionnaire.
AB  - BACKGROUND: Previous survey tools operationalising knowledge, attitudes or
      beliefs about evidence-based practice (EBP) have shortcomings in content,
      psychometric properties and target audience. AIMS: This study developed and
      psychometrically assessed a self-report trans-professional questionnaire to
      describe an EBP profile. METHODS: Sixty-six items were collated from existing EBP
      questionnaires and administered to 526 academics and students from health and non
      health backgrounds. Principal component factor analysis revealed the presence of
      five factors (Relevance, Terminology, Confidence, Practice and Sympathy).
      Following expert panel review and pilot testing, the 58-item final questionnaire
      was disseminated to 105 subjects on two occasions. Test-retest and internal
      reliability were quantified using intra-class correlation coefficients (ICCs) and
      Cronbach's alpha, convergent validity against a commonly used EBP questionnaire
      by Pearson's correlation coefficient and discriminative validity via analysis of
      variance (ANOVA) based on exposure to EBP training. RESULTS: The final
      questionnaire demonstrated acceptable internal consistency (Cronbach's alpha
      0.96), test-retest reliability (ICCs range 0.77-0.94) and convergent validity
      (Practice 0.66, Confidence 0.80 and Sympathy 0.54). Three factors (Relevance,
      Terminology and Confidence) distinguished EBP exposure groups (ANOVA p < 0.001
      0.004). CONCLUSION: The evidence-based practice profile (EBP(2)) questionnaire is
      a reliable instrument with the ability to discriminate for three factors, between
      respondents with differing EBP exposures.

PMID- 20795795
TI  - Apatite microtopographies instruct signaling tapestries for progenitor-driven new
      attachment of teeth.
AB  - Dimension and structure of extracellular matrix surfaces have powerful influences
      on cell shape, adhesion, and gene expression. Here we show that natural tooth
      root topographies induce integrin-mediated extracellular matrix signaling
      cascades in tandem with cell elongation and polarization to generate
      physiological periodontium-like tissues. In this study we replanted surface
      topography instructed periodontal progenitors into rat alveolar bone sockets for
      8 and 16 weeks, resulting in complete reattachment of tooth roots to the
      surrounding alveolar bone with a periodontal fiber apparatus closely matching
      physiological controls along the entire root surface. Displacement studies and
      biochemical analyses confirmed that progenitor-based engineered periodontal
      tissues were similar to control teeth and uniquely derived from preimplantation
      green fluorescent protein (GFP)-labeled progenitors. Together, these studies
      illustrate the capacity of natural extracellular surface topographies to instruct
      progenitor cell populations to fully regenerate complex cellular and structural
      morphologies of tissues once lost to disease. We suggest that our strategy could
      be used for the replantation of teeth lost due to trauma or as a novel approach
      for tooth replacement using tooth-shaped replicas.

PMID- 20795797
TI  - eLearning to enhance physician patient communication: a pilot test of "doc.com"
      and "WebEncounter" in teaching bad news delivery.
AB  - BACKGROUND: Physician-patient communication skills help determine the nature and
      quality of diagnostic information elicited from patients, the quality of the
      physician's counseling, and the patient's adherence to treatment. In spite of
      their importance, surveys have demonstrated a wide variability and deficiencies
      in the teaching of these skills. AIM: Describe two specific methodologies for
      teaching physician-patient communication skills developed at our institution and
      pilot test them for effectiveness. METHODS: Between 2004 and 2009 we developed
      "doc.com," a series of 41 media-rich online modules on all aspects of healthcare
      communication jointly with the American Academy on Communication in Healthcare.
      Starting in 2006, we expanded our pre-existing experience with the
      videoconferencing system "WebOSCE" into the online application "WebEncounter."
      This new methodology combines practice of communication skills on standardized
      patients with structured assessment and constructive feedback. We had three
      randomized groups: controls who did only the assessment parts of a WebOSCE on two
      occasions, a doc.com group who had doc.com in between the assessment occasions,
      and a combined group that had both doc.com and a WebEncounter between
      assessments. RESULTS/CONCLUSION: We found significant improvement in skills as
      components were added, and the training program was well received.

PMID- 20795798
TI  - Students' perceptions of interprofessional learning through facilitated online
      learning modules.
AB  - BACKGROUND: Asynchronous e-learning is an appealing option for interprofessional
      education (IPE) as it addresses the geographic and timetabling barriers often
      encountered when organizing activities across educational programs. AIM: This
      study examined the extent to which pre-licensure students were able to learn
      with, from, and about each other through completion of innovative online IPE
      learning modules. METHODS: Seventy-seven students completed e-learning modules
      developed through a consortium of educational institutions. Evaluation was
      primarily qualitative through focus groups, interviews, analyses on off-line
      discussions and an online feedback form. RESULTS: Qualitative analyses of the
      discussion fora revealed that students were able to solve problems
      collaboratively, clarify their professional roles, and provide information from
      their professional perspective. Focus groups and interviews reinforced that
      students recognized the importance of working together and implicate clinical
      education as an important venue to reinforce learning about collaborative
      practice. Analyses of the online feedback form suggest the need for clear
      processes related to group assignments and deadlines. CONCLUSION: Students
      learned about each other's role, solved problems together and had positive
      perceptions of the online modules as a venue for interprofessional learning.
      Results are encouraging to those interested in using e-learning in IPE as part of
      an overall curriculum.

PMID- 20795799
TI  - This is the closest I have come to being compared to a doctor: views of medical
      students on clinical clerkship in an Interprofessional Training Unit.
AB  - BACKGROUND: The need for interprofessional education has been apparent for
      decades and in 2004, we established the first Interprofessional Training Unit
      (ITU) in Denmark. Nursing, occupational therapy and physiotherapy students were
      in the ITU for its first 2 years and in 2006, medical students joined in. The
      students in collaboration run a ward with eight beds under the supervision of
      trained personnel. METHODS: A questionnaire consisting questions concerning the
      interprofessional meetings, the rounds, teaching, learning about own profession,
      learning about other professions and finally an overall assessment of their stay
      in the ITU was filled in by 55 medical students. To validate and deepen the
      questionnaire, 22 medical students participated in a group interview
      concentrating on the students' evaluation of fulfilment of the goals for the ITU.
      The transcripted interview and the written comments in the questionnaire were
      analysed using Systematic Text Condensation. RESULTS: Our results showed that the
      medical students in the ITU developed their professional knowledge and capability
      simultaneous with the learning of interprofessional collaboration. The students
      valued the teaching methods because the students were in the forefront and
      treated as professionals. The students demanded more homogeneous instruction and
      a better introduction to the ITU. CONCLUSION: A stay in an ITU with a safe
      learning environment can increase both uniprofessional and interprofessional
      learning for medical students. The students stressed the importance of
      supervision before and after carrying out a hospital task.

PMID- 20795800
TI  - Professionalism is a generic term: practicing what we preach.

PMID- 20795801
TI  - Effective small group learning: AMEE Guide No. 48.
AB  - The objective of this educational guide is to outline the major facets of
      effective small group learning, particularly applied to medicine. These are
      discussion skills, methods, the roles and responsibilities of tutors and
      students, the dynamics of groups and the effects of individuals. It is argued
      that the bases of effective small group learning are discussion skills such as
      listening, questioning and responding. These skills are the platform for the
      methods of facilitating discussion and thinking. The facilitating methods
      strengthen the generic methods, such as tutorials, seminars and electronic
      tutorials. However, the success of these methods is dependent in part upon the
      roles and responsibilities taken by students and tutors and the consequent group
      dynamic. The group dynamic can be adversely affected by individuals. Evaluation
      of the processes of small group learning can provide diagnoses of the behaviour
      of difficult individuals. More importantly, studies of the processes can help to
      develop more effective small group learning.

PMID- 20795802
TI  - The changing landscape of medical education in the UK.
AB  - The UK shares many characteristics with other western developed countries,
      including a current adherence to the view that defining educational outcomes
      enables improvements in learning and teaching and a more effective management of
      the learning and assessment process. There are, however, some features that make
      UK medical education unique or that give it a distinctive flavour. This article
      looks at the various forces that shape medical education in the UK and the
      structures that underpin its delivery, and discusses the distinctive climate that
      is produced, in which doctors, students and medical teachers are expected to
      work. We examine and assess these special features of UK medical education and
      report on the ways in which medical education and medical educators are adapting
      to the complex and constantly changing environment. We conclude that the
      healthcare and higher education systems in the UK face unprecedented economic and
      political challenges over the coming years. Medical educators working within
      these systems have an important role in ensuring that these challenges are met
      and that standards are maintained and improved. A stronger professional
      architecture to support careers in medical education is needed to ensure that
      those involved in teaching medical students and doctors have the necessary
      training, time, resources and incentives to do it effectively.

PMID- 20795803
TI  - Promoting professional behaviour in undergraduate medical, dental and veterinary
      curricula in the Netherlands: evaluation of a joint effort.
AB  - BACKGROUND: From 2002 onwards, a nationwide working group of representatives from
      all medical (8), dental (3) and veterinary medicine (1) schools collaborated in
      order to develop and implement recommendations for teaching and assessing
      professional behaviour. AIM: The aim of this article is to describe the outcomes
      of this process, including hurdles encountered and challenges to be met. METHOD:
      By a qualitative survey, information was requested on teaching professional
      behaviour, assessment, instruments used, consequences of unprofessional behaviour
      and faculty training. RESULTS: All schools have adopted at least parts of the
      2002 recommendations. Differences exist mainly in the organisational structure of
      teaching and assessment as well as in the assessment instruments used. In all
      schools a longitudinal assessment of professional behaviour was accomplished.
      CONCLUSION: All schools involved have made progress since 2002 with regard to
      teaching and assessment of professional behaviour, resulting in a shift from an
      instrumental to a cultural change for some schools. A stimulating factor was
      society's call to focus on patient safety and therefore on assessment of
      unprofessional behaviour. Hurdles yet to be taken are the involvement of students
      in the assessment process, teacher confidence in personal assessment capacities,
      remediation programmes and logistic and administrative support.

PMID- 20795804
TI  - What has changed in the evidence for early experience? Update of a BEME
      systematic review.
AB  - BACKGROUND: We previously reviewed evidence published from 1992 to 2001
      concerning early experience for healthcare undergraduates (Dornan T, Littlewood
      S, Margolis S, Scherpbier A, Spencer J, Ypinazar V. 2006. How can experience in
      clinical and community settings contribute to early medical education? A BEME
      systematic review. Med Teach 28:3-18). This subsequent study reviews evidence
      published from 2002 to 2008. AIMS: Identify changes in the evidence base;
      determine the value of re-reviewing; set a future research agenda. METHODS: The
      same search strategy as in the original review was repeated. Newly identified
      publications were critically appraised against the same benchmarks of strength
      and educational importance. RESULTS: Twenty-four new empirical studies of early
      authentic experience in education of health professionals met our inclusion
      criteria, yielding 96 outcomes. Sixty five outcomes (from 22 studies) were both
      educationally important and based on strong evidence. A new significant theme was
      found: the use of early experience to help students understand and align
      themselves with patient and community perspectives on illness and healthcare.
      More publications were now from outside Europe and North America. CONCLUSIONS: In
      addition to supporting the findings of our original review, this update shows an
      expansion in research sources, and a shift in research content focus. There are
      still questions, however, about how early authentic experience leads to
      particular learning outcomes and what will make it most educationally effective.

PMID- 20795805
TI  - Does sharing information before a clinical skills examination impact student
      performance?
AB  - BACKGROUND: Clinical performance examinations (CPX) often must be administered
      over several sessions to accommodate a large number of students, resulting in the
      potential for breaches in examination security. AIMS: This study addressed the
      impact of information sharing by medical students on CPX scores. METHOD:
      Questionnaires about prior knowledge of diagnosis related to the case
      (Questionnaire I), and information sharing across the examination (Questionnaire
      II) were obtained. The students were categorized into two groups: prior knowledge
      of the diagnosis or information sharing. RESULTS: 54.5% students received some
      information before the CPX, and 55.9% among them obtained information in the form
      of printed documents. Many students obtained information about the diagnosis and
      the information was helpful. There were no statistical differences in the scores
      between two groups. 25-30 % of the students thought they had prior knowledge of
      the diagnosis of each case before the CPX. CONCLUSION: More than half of the
      students obtained some information before taking the CPX regarding the
      examination content. The impact of information sharing on CPX scores was
      negligible. My findings support the importance of the application of knowledge
      and the demonstration of skills that are highlighted in this assessment.

PMID- 20795806
TI  - Teaching social determinants of child health in a pediatric advocacy rotation:
      small intervention, big impact.
AB  - BACKGROUND: Traditionally, medical education does not specifically address the
      social determinants of health or how to advocate for families' cultural, social
      or economic needs in spite of our increasingly diverse society. AIM: This article
      describes a new social-legal curriculum added to a Pediatric Resident's Advocacy
      course. METHODS: Pediatric interns completed 'Memos To Myself' after the Advocacy
      rotation. RESULTS: The curriculum impacted residents' (1) realization regarding
      family circumstances; (2) reflections regarding self and personal practice; and
      (3) knowledge about advocacy issues and community partnerships for solutions.
      CONCLUSIONS: This curriculum raised awareness about topics that are traditionally
      not covered in medical education.

PMID- 20795807
TI  - Advantages of video trigger in problem-based learning.
AB  - BACKGROUND: Traditionally, paper cases are used as 'triggers' to stimulate
      learning in problem-based learning (PBL). However, video may be a better medium
      because it preserves the original language, encourages the active extraction of
      information, avoids depersonalization of patients and allows direct observation
      of clinical consultations. In short, it exposes the students to the complexity of
      actual clinical problems. AIM: The study aims to find out whether students and
      facilitators who are accustomed to paper cases would prefer video triggers or
      paper cases and the reasons for their preference. METHOD: After students and
      facilitators had completed a video PBL tutorial, their responses were measured by
      a structured questionnaire using a modified Likert scale. RESULTS: A total of 257
      students (92%) and 26 facilitators (100%) responded. The majority of students and
      facilitators considered that using video triggers could enhance the students'
      observational powers and clinical reasoning, help them to integrate different
      information and better understand the cases and motivate them to learn. They
      found PBL using video triggers more interesting and preferred it to PBL using
      paper cases. CONCLUSION: Video triggers are preferred by both students and
      facilitators over paper cases in PBL.

PMID- 20795808
TI  - Perspectives on using multimedia scenarios in a PBL medical curriculum.
AB  - In 1999, the Faculty of Health Sciences at Linkoping University, Sweden, started
      up a process of replacing text-based problem-based learning (PBL) scenarios with
      web-based multimedia-enhanced scenarios. This article brings together three
      studies of the results of this process and the experience gained from 10 years of
      implementation work. RESULTS AND CONCLUSIONS: Adding multimedia to PBL scenarios
      makes them more realistic and thereby more motivating and stimulating for the
      student to process. The group process is not disrupted by the introduction of the
      computer in the group room. It is important to challenge the students by varying
      the scenarios' perspective and design in order to get away from cue-seeking
      behaviors that might jeopardize a deep approach to learning. Scrutinizing all
      scenarios in a PBL curriculum can be used as a tool for improvement and renewal
      of the entire curriculum.

PMID- 20795809
TI  - A multi-institutional survey of internal medicine residents' learning habits.
AB  - BACKGROUND: Resident physicians are expected to demonstrate medical knowledge.
      However, little is known about the residents' reading habits and learning
      preferences. AIM: To assess residents' reading habits and preferred educational
      resources. METHODS: Residents at five internal medicine training programs were
      surveyed regarding their reading and learning habits and preferences. RESULTS:
      The majority (77.7%) of residents reported reading less than 7 h a week. Most
      residents (81.4%) read in response to patient care encounters. The preferred
      educational format was electronic; 94.6% of residents cited UpToDate as the most
      effective resource for knowledge acquisition, and 88.9% of residents reported
      that UpToDate was their first choice for answering clinical questions.
      CONCLUSIONS: Residents spent little time reading and sought knowledge primarily
      from electronic resources. Most residents read in the context of patient care.
      Future research should focus on strategies for helping resident physicians learn
      in the electronic age.

PMID- 20795810
TI  - Personalization enhances learning anatomy terms.
AB  - BACKGROUND: Personalizing computer-based instructional text with a conversational
      rather than formal style has been found to enhance learning substantially. AIM:
      An experimental study investigated whether a conversational style would enhance
      learning anatomy terminology from paper-based materials. METHODS: Students were
      randomly assigned to experimental conditions, and hypotheses were tested with a
      multiple-choice test and self-report scales. RESULTS: Studying personalized
      materials led to better performance on a terminology test and lower mental effort
      during testing than studying non-personalized materials. However, groups did not
      differ on ratings of interest/enjoyment. CONCLUSION: These results extend
      previous research by demonstrating learning gains following personalization using
      paper-based materials. However, the lack of effect on interest/enjoyment self
      reports raises questions about previous theorizing on the role of this variable.

PMID- 20795811
TI  - Stability of values during medical school.
AB  - BACKGROUND: Medical students' values represent an understudied area of research
      in medical education research. No known studies have investigated how medical
      students' values change over time from matriculation to graduation. AIM: Values
      are thought to remain relatively stable over the life course. However, little
      research supports this claim. Therefore, we examined the extent to which values
      change or remain the same during medical school. METHOD: Forty-six first-year
      medical students completed the Physician Values in Practice Scale (PVIPS) during
      their first and fourth years of medical school. The PVIPS contains 38 statements
      of values about medical practice and comprises six scales: Prestige, Service,
      Autonomy, Lifestyle, Management, and Scholarly Pursuits. RESULTS: Matched pair t
      tests (p < 0.05) indicated significant differences between students' PVIPS scores
      pretest (first year of medical school) and posttest (fourth year of medical
      school) for 2 of the 6 values (Autonomy: t(45) = -4.12, p < 0.001 and Lifestyle:
      t(45) = -2.62, p = 0.012). CONCLUSIONS: Medical students values appear to change
      slightly during their 4 years of medical education. In line with literature
      suggesting that the medical education process is associated with change in
      certain student qualities and attributes (e.g., empathy), physician values may be
      another variable so affected.

PMID- 20795812
TI  - PerSIST: a PAL system for clinical skills training: a planning and implementation
      framework: Guide Supplement 30.8--practical application.

PMID- 20795813
TI  - Peer-assisted learning: a planning and implementation framework. Guide supplement
      30.7--practical application.

PMID- 20795814
TI  - Workplace-based assessment as an educational tool: Guide supplement 31.3-
      viewpoint.

PMID- 20795815
TI  - Professor Bjorn Bergdahl --a pioneer in Swedish medical education.

PMID- 20795816
TI  - Student generated questions drive learning in the classroom.

PMID- 20795817
TI  - Virtual reality in medical education.

PMID- 20795820
TI  - Priming the immune system for heart disease: a perspective on group A
      streptococci.
AB  - Although immune responses against group A streptococci and the heart have been
      correlated with antibodies and T cell responses against cardiac myosin, there is
      no unifying hypothesis about carditis caused globally by many different
      serotypes. Our study identified disease-specific epitopes of human cardiac myosin
      in the development of rheumatic carditis in humans. We found that immune
      responses to cardiac myosin were similar in rheumatic carditis among a small
      sample of worldwide populations, in which immunoglobulin G targeted human cardiac
      myosin epitopes in the S2 subfragment hinge region within S2 peptides containing
      amino acid residues 842-992 and 1164-1272. An analysis of rheumatic carditis in a
      Pacific Islander family confirmed the presence of potential rheumatogenic
      epitopes in the S2 region of human cardiac myosin. Our report suggests that
      cardiac myosin epitopes in rheumatic carditis target the S2 region of cardiac
      myosin and are similar among populations with rheumatic carditis worldwide,
      regardless of the infecting group A streptococcal M serotype.

PMID- 20795821
TI  - Prediction of preeclampsia and delivery of small for gestational age babies based
      on a combination of clinical risk factors in high-risk women.
AB  - OBJECTIVE: To develop clinical risk tools for preeclampsia and small for
      gestational age (SGA) in high-risk women. METHODS: Individual risk scores based
      on clinical risk factors were calculated using logistic regression and validated
      in 1687 women with obesity in first pregnancy, chronic hypertension, or previous
      preeclampsia. RESULTS: The risk of preeclampsia varied from 7% in obese
      primiparae without hypertension to 30% when previous preeclampsia and chronic
      hypertension occurred together. A prediction model incorporating these risk
      factors had a sensitivity of 48 and 89% for preeclampsia delivered <34 weeks'
      gestation. CONCLUSION: Multiple clinical risk factors increase the risk of
      preeclampsia and SGA.

PMID- 20795819
TI  - A randomized clinical trial comparing revaccination with pneumococcal conjugate
      vaccine to polysaccharide vaccine among HIV-infected adults.
AB  - BACKGROUND: The risk of pneumococcal disease persists, and antibody responses to
      revaccination with the 23-valent polysaccharide vaccine (PPV) are low among human
      immunodeficiency virus (HIV)-infected adults. We determined whether revaccination
      with the 7-valent pneumococcal conjugate vaccine (PCV) would enhance these
      responses. METHODS: In a randomized clinical trial, we compared the
      immunogenicity of revaccination with PCV ( n = 131) or PPV (n = 73) among HIV
      infected adults (median CD4 cell count, 533 cells/mm(3)) who had been vaccinated
      with PPV 3-8 years earlier. HIV-uninfected adults (n = 25) without prior
      pneumococcal vaccination received 1 dose of PCV. A positive response was defined
      as a >or=2-fold increase (from baseline to day 60) in capsule-specific
      immunoglobulin G, with a postvaccination level >or=1000 ng/mL for at least 2 of
      the 4 serotypes. RESULTS: HIV-infected persons demonstrated a higher frequency of
      positive antibody responses to PCV than to PPV (57% vs 36%) (P = .004) and
      greater mean changes in the immunoglobulin G concentration from baseline to day
      60 for serotypes 4, 9V, and 19F (P < .05, for all), but not for serotype 14.
      However, by day 180, both outcomes were similar. Responses to PCV were greater in
      frequency and magnitude for all serotypes in HIV-uninfected adults, compared with
      those in HIV-infected adults. CONCLUSIONS: Among persons with HIV infection,
      revaccination with PCV was only transiently more immunogenic than PPV, and
      responses were inferior to those in HIV-uninfected subjects with primary
      vaccination. Pneumococcal vaccines with more robust and sustained immunogenicity
      are needed for HIV-infected adults. Clinical trial registration.
      ClinicalTrials.gov identifier NCT00622843.

PMID- 20795822
TI  - Urinary excretion of nephrin in patients with severe preeclampsia. Urinary
      nephrin in preeclampsia.
AB  - OBJECTIVE: The objective of this study was to examine whether nephrin is present
      in the urine of patients with severe preeclampsia. METHODS: A total of 45 women
      were recruited for this study, and 25 of these patients had severe preeclampsia.
      Twenty gestational age-matched normotensive women without proteinuria served as a
      control group. Urine samples were collected close to delivery, typically <=24 h
      before delivery. Western blot analysis was performed to assess the excretion of
      nephrin in urine. RESULTS: Nephrin was detected in all urine samples from all the
      women with severe preeclampsia but not in urine from normotensive controls.
      CONCLUSION: In pregnancy complicated by severe preeclampsia, urinary nephrin
      shedding, reflecting the damage in the glomerular slit diaphragm, was observed.

PMID- 20795823
TI  - Interprofessional staff development: changing attitudes and winning hearts and
      minds.
AB  - As more educators are involved in interprofessional education (IPE) it is
      important to consider how participation affects those who are sceptical about
      IPE. We report a prospective study in which the attitudes of 13 educators,
      unfamiliar with IPE, were compared before and after facilitating their first IPE.
      Their views, obtained as personal stories, were analysed through cognitive
      dissonance theory. Prior to teaching, all novice educators had concerns about
      IPE. Post-facilitation all were more positive about the value and meaning of IPE.

PMID- 20795824
TI  - Beyond curriculum: embedding interprofessional collaboration into academic
      culture.

PMID- 20795828
TI  - Developing theory and practice: creation of a Community of Practice through
      Action Research produced excellence in stroke care.
AB  - Much emphasis is placed on expert knowledge like evidence-based stroke
      guidelines, with insufficient attention paid to processes required to translate
      this into delivery of everyday good care. This paper highlights the worth of
      creating a Community of Practice (CoP) as a means to achieve this. Drawing on
      findings from a study conducted in 2000-2002 of processes involved in
      establishing a nationally lauded high quality Stroke Unit, it demonstrates how
      successful development of a new service was linked to creation of a CoP. Recent
      literature suggests CoPs have a key in implementing evidence-based practice; this
      study supports this claim whilst revealing for the first time the practical
      knowledge and skills required to develop this style of working. Findings indicate
      that participatory and democratic characteristics of Action Research are
      congruent with the collaborative approach required for developing a CoP. The
      study is an exemplar of how practitioner researchers can capture learning from
      changing practice, thus contributing to evidence-based healthcare with
      theoretical and practical knowledge. Findings are relevant to those developing
      stroke services globally but also to those interested in evidence-based practice.

PMID- 20795829
TI  - Examining the interface between interprofessional practice and education: lessons
      learned from Norway for promoting teamwork.
AB  - Promoting teamwork in health and social care requires an understanding of the
      interface between interprofessional practice (IPP) and interprofessional
      education (IPE). A study with two parts, one qualitative and one quantitative,
      examined this interface in Norway. The first used focus groups to assess IPP
      rewards, barriers, and facilitating factors among practitioners in clinical
      settings. The second utilized an online survey to measure IPE attitudes,
      barriers, and facilitating factors among senior administrators in the educational
      system. Results of Part 1 indicate that providers report many intrinsic rewards
      of IPP; however, the more extrinsic impacts of collaborative practice on patient
      care need to be emphasized to system managers. Results of Part 2 suggest strong
      general support by academic deans and directors for IPE, though addressing
      specific potential barriers to its implementation has become increasingly
      important. Overall, bridging the IPP-IPE gap requires educating leaders in both
      settings about the resources needed for teamwork, linking clinical and
      educational settings through continuing professional development, and generally
      advocating more effectively for both IPP and IPE.

PMID- 20795830
TI  - Conflict on interprofessional primary health care teams--can it be resolved?
AB  - Increasingly, primary health care teams (PHCTs) depend on the contributions of
      multiple professionals. However, conflict is inevitable on teams. This article
      examines PHCTs members' experiences with conflict and responses to conflict. This
      phenomenological study was conducted using in-depth interviews with 121
      participants from 16 PHCTs (10 urban and 6 rural) including a wide range of
      health care professionals. An iterative analysis process was used to examine the
      verbatim transcripts. The analysis revealed three main themes: sources of team
      conflict; barriers to conflict resolution; and strategies for conflict
      resolution. Sources of team conflict included: role boundary issues; scope of
      practice; and accountability. Barriers to conflict resolution were: lack of time
      and workload; people in less powerful positions; lack of recognition or
      motivation to address conflict; and avoiding confrontation for fear of causing
      emotional discomfort. Team strategies for conflict resolution included
      interventions by team leaders and the development of conflict management
      protocols. Individual strategies included: open and direct communication; a
      willingness to find solutions; showing respect; and humility. Conflict is
      inherent in teamwork. However, understanding the potential barriers to conflict
      resolution can assist PHCTs in developing strategies to resolve conflict in a
      timely fashion.

PMID- 20795832
TI  - Challenges and benefits in implementing shared inter-agency assessment across the
      UK: a literature review.
AB  - Over the past 10 years, each of the four countries in the UK has attempted to
      resolve continuing difficulties with duplication of assessment and lack of shared
      information in community care, by developing approaches to shared assessment.
      Relevant literature reviews have previously focused on challenges to partnership
      working between health and social care, and on different approaches to
      assessment. The literature review described here differs in three key respects.
      Firstly, the literature was selected on the basis that it addressed shared
      assessment specifically. Secondly, it included evidence from the four countries
      within the UK, providing a cross-national basis to the evidence. Thirdly, this
      study was undertaken to identify whether benefits from shared assessment were
      evident, in addition to the challenges. While the evidence of benefits at this
      stage is relatively limited, it is clear that some have emerged, including two
      relating directly to relevant policy objectives: improved communication, service
      user and carer involvement; improved partnership and joined up working. As
      approaches to shared assessment are currently under review in Scotland, England
      and Wales, and implementation underway in Northern Ireland, and in light of the
      economic recession and demographic challenges, consideration of key aspects of
      the evidence may be timely.

PMID- 20795833
TI  - An evaluation of practice-based interprofessional education initiatives involving
      service users.
AB  - There is little published evidence regarding the impact of service-user focused
      interprofessional education in the practice setting. This article reports
      evaluative case studies of two practice-based interprofessional initiatives, in
      which service users played a central role. These initiatives formed part of the
      Trent Universities Interprofessional Learning in Practice (TUILIP) project (
      http://tuilip.hwb.shu.ac.uk ), a collaboration between Sheffield Hallam
      University and the University of Nottingham. Practice settings were an acute
      mental health service and a community organisation offering care and services to
      adults with learning disabilities. Interprofessional initiatives were developed
      by facilitators, and empirically studied at each site. Facilitators, managers,
      practitioners, students and service users took part in interviews and focus
      groups to discuss their perceptions of the initiative in their practice setting.
      The study revealed participants' perceptions of the projects' aims, process and
      outcomes, factors which facilitated success or proved challenging, and their
      impact upon individuals, clinical practice and the organisations involved.

PMID- 20795831
TI  - Matrisibs, patrisibs, and the evolution of imprinting on autosomes and sex
      chromosomes.
AB  - The conflict theory of genomic imprinting argues that parent-of-origin effects on
      allelic expression evolve as a consequence of conflict between maternally and
      paternally derived genomes. I derive explicit population-genetic models of this
      theory when individuals in a cohort with an arbitrary and variable number of
      sires and dams interact. I show that the evolution of imprinting is governed by
      the reciprocal of the harmonic mean number of fathers but the reciprocal of the
      arithmetic mean number of mothers per cohort. Thus, a few monandrous females in a
      polyandrous population decrease the strength of the genetic conflict and the
      opportunity for conflict-driven paternal imprinting. In contrast, in populations
      in which few males control large harems, rare males with small harems do not have
      such a disproportionate effect on genetic conflicts and maternal imprinting.
      Additionally, I demonstrate that under the conflict theory, selection for
      imprinted expression on paternally derived X chromosomes is much weaker than it
      is on maternally derived X chromosomes or autosomes.

PMID- 20795834
TI  - Students' reflections on shadowing interprofessional teamwork: a Norwegian case
      study.
AB  - This article reports the students' reflections on interprofessional teamwork
      during brief exposures to real-life experiences in hospitals or home-based
      rehabilitation service. Each of the 10 interprofessional groups, comprising three
      students, followed a rehabilitation team for a day. The composition of each
      student group correlated with the rehabilitation team. Data were collected from
      interviews with the student groups and subjected to a thematic analysis. The
      following four main themes were identified for which the students seemed to
      affect collaboration: sharing knowledge; team setting and position within the
      organisation; patient centred focus; and challenges in crossing professional
      borders when performing tasks. Each of these themes is presented and discussed in
      relation to the educational literature. In conclusion, the data suggest that a
      well organized, one-day observation-based learning experience helped to motivate
      students and helped to enable them to relate theory and practice.

PMID- 20795836
TI  - Impermeable boundaries? Developments in professional and inter-professional
      practice.
AB  - The nature of the professional task in welfare services is constantly changing.
      These changes are not confined to Britain but are widespread across the developed
      world and include initiatives to develop new professional roles and redesign
      existing services. Central to these initiatives is an assumption that the
      professions, and the individual professionals involved, will be willing and able
      to adapt their professional practice. The challenges inevitably posed by these
      developments appear to have been played down, particularly in respect of the role
      played by the boundaries between professions. This article considers the nature
      of boundaries before exploring these service developments as a means to highlight
      the issues they raise. The article contends that for these developments to work
      we need to move beyond the current focus on the role of education, training and
      regulation which structure professional boundaries to appreciate the 'human and
      social aspects' of these changes in order to understand how individual
      professionals perceive and experience the boundaries between professional groups.

PMID- 20795835
TI  - Interprofessionalism and shared decision-making in primary care: a stepwise
      approach towards a new model.
AB  - Most shared decision-making (SDM) models within healthcare have been limited to
      the patient-physician dyad. As a first step towards promoting an
      interprofessional approach to SDM in primary care, this article reports how an
      interprofessional and interdisciplinary group developed and achieved consensus on
      a new interprofessional SDM model. The key concepts within published reviews of
      SDM models and interprofessionalism were identified, analysed, and discussed by
      the group in order to reach consensus on the new interprofessional SDM (IP-SDM)
      model. The IP-SDM model comprises three levels: the individual (micro) level and
      two healthcare system (meso and macro) levels. At the individual level, the
      patient presents with a health condition that requires decision-making and
      follows a structured process to make an informed, value-based decision in concert
      with a team of healthcare professionals. The model acknowledges (at the meso
      level) the influence of individual team members' professional roles including the
      decision coach and organizational routines. At the macro level it acknowledges
      the influence of system level factors (i.e. health policies, professional
      organisations, and social context) on the meso and individual levels.
      Subsequently, the IP-SDM model will be validated with other stakeholders.

PMID- 20795837
TI  - A city-wide approach to cross-boundary working with students with mental health
      needs.
AB  - The aim of the research was to study a city-wide approach to meet the mental
      health needs of UK students involving a range of professional and non
      professional support. The creation of a network for agencies and individuals
      concerned with the mental health of students in further and higher education
      offered an opportunity to examine issues of access to services, transitions
      between services and the need for inter-agency working. The attitudes and
      experiences of a range of professional and non-professional providers of support
      were explored using semi-structured interviews within a multiple case study
      methodological approach. Inter-agency working across professional and
      organisational boundaries was believed to offer the best means of enabling
      students with mental health needs to continue with their studies. However, issues
      of resources limitations, professional identities, work boundaries, role
      confusion, codes of ethics and confidentiality presented barriers to integrated
      support and inter-professional collaboration.

PMID- 20795838
TI  - Innovations in interprofessional education and collaboration in a West Australian
      community health organisation.
AB  - This article is a short report that describes an initiative in interprofessional
      education (IPE) and collaboration in health practices in a community health
      organisation. Staff and students from nursing and allied health professions
      collaborate to implement a video feedback parenting programme. The results
      include an increased awareness of the benefits of both IPE and infant mental
      health principles, in particular the establishment of a common language across
      professions. Further systematic evaluations are required.

PMID- 20795839
TI  - An instrument for measuring pharmacist and physician attitudes towards
      collaboration: preliminary psychometric data.
AB  - This study was designed to develop an instrument for measuring attitudes toward
      pharmacist-physician collaborative relationships for administration to practicing
      pharmacists and physicians, as well as to students in pharmacy and medical
      schools. Based on a review of literature, a preliminary version of an instrument
      was developed (30 items), and through a pilot study of face validity and content
      validity with 12 pharmacists and 10 physicians, 18 items were chosen for
      quantitative analyses. We asked 88 respondents (61 pharmacists, 27 physicians) to
      judge the relevance, clarity, and representativeness of each item to the concept
      of pharmacist-physician collaborative relationships. Sixteen items with a
      relevancy endorsement greater than 85% and significant item-total score
      correlations were retained. The following underlying constructs emerged from
      factor analysis: "collaboration and team work," "accountability," "overlapping
      responsibility," and "authority". These factors supported the multidimensionality
      and construct validity of the instrument. No gender difference was observed;
      however, pharmacists scored higher than physicians on the total score of the
      instrument. The Cronbach's coefficient alpha was .81 for pharmacists, .92 for
      physicians, and .87 for the combined sample. Encouraged by these preliminary
      findings, we plan to undertake further research to examine the instrument's
      psychometric properties including criterion-related and predictive validities
      with larger and more representative samples of pharmacists, physicians, and
      students in pharmacy and medical schools.

PMID- 20795840
TI  - Decision making and co-operation between stakeholders within the process of sick
      leave. A case study in a Danish municipality.
AB  - The study addresses how recent reforms of the Sickness Benefit Act in Denmark are
      put into practice. A single case study embedded with five subunits of analysis
      based on "real life" cases has been conducted in a Danish municipality. Five
      "sick-listed" citizens and their respective municipal case manager and general
      practitioner (GP) were interviewed. Two key persons within the municipality were
      interviewed as background informants. The GPs and case managers ability to co
      operate was hampered by lack of time, frequent staff turnover, lack of financial
      resources, and low accessibility. The motivation for co-operation was low due to
      low status of social medical issues, lack of feedback and lack of trust. The co
      operation was characterized by sequential task integration. The stakeholders
      encountered difficulties when reciprocal task integration was needed. The
      decision making was affected by legal constraints and conflicting paradigms of
      key stakeholders. Rather than forcing co-operation, policymakers should increase
      the stakeholders' abilities and improve the conditions that create the low level
      of trust and hamper the willingness to co-operate.

PMID- 20795841
TI  - Role of dronedarone in atrial fibrillation: more questions than answers.

PMID- 20795842
TI  - Atenolol exposure and risk for development of adverse metabolic effects: a pilot
      study.
AB  - STUDY OBJECTIVE: To evaluate whether the level of systemic exposure to atenolol
      explains observed interindividual differences in adverse metabolic responses.
      DESIGN: Open-label, prospective, pharmacokinetic pilot substudy of the
      Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study. SETTING:
      General clinical research center. PATIENTS: Fifteen hypertensive adults (mean age
      46 +/- 8.9 yrs) who were enrolled in the PEAR study. INTERVENTION: Patients
      received atenolol therapy for at least 8 weeks, with 5 of those weeks at a dosage
      of 100 mg/day, and then underwent a 2-hour oral glucose tolerance test during a
      pharmacokinetic study visit. MEASUREMENTS AND MAIN RESULTS: Twenty-hour plasma
      atenolol concentrations were measured during the pharmacokinetic visit. Glucose
      and insulin levels were measured during the 2-hour oral glucose tolerance test,
      and fasting plasma lipid, glucose, and insulin levels were measured at baseline
      and after 8 weeks of atenolol treatment. A significant association was noted
      between atenolol area under the concentration-time curve (AUC) and change in
      fasting glucose level when adjusted for covariates (p=0.0025); the effect was
      strongest in women. No significant relationship was noted between plasma atenolol
      concentration and glucose AUC during oral glucose tolerance testing (r=0.08,
      p=0.78), nor between atenolol AUC and change in triglyceride levels (r=0.13,
      p=0.63). CONCLUSION: Higher plasma atenolol exposure may be a risk factor for an
      increase in fasting plasma glucose level during atenolol treatment. These
      findings require confirmation in a larger sample.

PMID- 20795843
TI  - Synergistic effect of statins and postmenopausal hormone therapy in the
      prevention of skeletal fractures in elderly women.
AB  - STUDY OBJECTIVE: To examine the role of concurrent 3-hydroxy-3-methylglutaryl
      coenzyme A reductase inhibitor (statin) use and postmenopausal hormone therapy on
      osteoporosis-related fractures. DESIGN: Case-control study. Data Source. Large
      integrated health plan in New Mexico. Patients. Case patients were 1001 women
      with incident fractures of the hip, wrist, forearm, or spine that occurred
      between January 1, 2000, and December 31, 2005, and controls were 2607 women
      without fractures during the same time frame; both groups were selected from the
      same population of women aged 50 years or older who utilized health plan services
      during the study time frame. MEASUREMENTS AND MAIN RESULTS: Postmenopausal
      hormone therapy use was classified as "current" (12 mo before index date) or
      "never or past." The risk of fractures was ascertained among continuous (> or =
      80% medication possession ratio during 12 mo before the index date) and current
      (3 mo before index date) statin users relative to patients without hyperlipidemia
      who did not use lipid-lowering drugs. The interaction between statins and hormone
      therapy was examined in multivariable logistic regression. The association
      between statin use and fractures was examined separately among current and never
      or past hormone therapy users after controlling for other risk factors. Nineteen
      percent of the study participants were current hormone therapy users; 9.5% were
      current and 4.8% were continuous statin users. No association between continuous
      statin use and fractures was observed among never or past hormone therapy users
      (odds ratio [OR] 0.80, 95% confidence interval [CI] 0.53-1.22). In contrast, a
      strong protective effect (OR 0.19, 95% CI 0.04-0.87) was observed among women who
      concurrently used statins and hormone therapy for 1 year, independent of age;
      corticosteroid, bisphosphonate, thiazide diuretic, calcitonin, methotrexate, or
      antiepileptic drug use; chronic kidney disease; and Charlson comorbidity index.
      CONCLUSION: Concurrent statin use and hormone therapy may have a synergistic
      protective effect on skeletal fractures beyond the additive effect of each
      individual therapy.

PMID- 20795844
TI  - Drug adsorption efficacy and palatability of a novel charcoal cookie formulation.
AB  - STUDY OBJECTIVES: To determine the effect of a novel charcoal cookie formulation
      compared with a standard aqueous charcoal product on the absorption of orally
      administered cimetidine, and to compare the palatability of the two charcoal
      products. DESIGN: Prospective, open-label, three-way, crossover trial. SETTING:
      General clinical research center. SUBJECTS: Eight healthy volunteers (five men,
      three women; mean age 23.4 yrs). INTERVENTION: After an overnight fast, each
      subject ingested a single cimetidine 800-mg tablet. Fifteen minutes later,
      subjects were randomly assigned to receive either water (control), three charcoal
      cookies (equivalent to 7.2 g of charcoal), or 7.2 g of aqueous activated charcoal
      suspension. Subjects then received each of the other study treatments-cimetidine
      with water, cimetidine with charcoal cookies, and cimetidine with charcoal
      suspension-separated by a 1-week washout period between each treatment.
      MEASUREMENTS AND MAIN RESULTS: Venous blood samples were obtained before and 8
      hours after administration of the cimetidine dose. Noncompartmental
      pharmacokinetic analysis was performed, and area under the plasma concentration
      time curve (AUC) and maximum plasma concentration (C(max)) were compared for each
      study drug combination. In addition, subjects evaluated the palatability of each
      charcoal product by using a visual analog scale. Both charcoal products
      effectively adsorbed cimetidine, resulting in decreased absorption of most of the
      cimetidine dose. No significant difference was noted in the median percent
      decrease in cimetidine AUC between the charcoal suspension and charcoal cookie
      (91.8% vs 82.1%, p=0.505). Similarly, no significant difference was noted in the
      median percent decrease in C(max) between the two charcoal formulations (82.6% vs
      64.0%, p=0.574). The palatability scores, however, were significantly higher for
      the charcoal cookie than for the charcoal suspension. All study drugs were well
      tolerated, and no adverse events were reported. CONCLUSION: The new charcoal
      cookie formulation appears to be as effective as the aqueous charcoal suspension
      at reducing absorption of cimetidine. In addition, the charcoal cookie was rated
      as more palatable than the aqueous charcoal suspension, suggesting that the
      charcoal cookie could be an attractive alternative to the charcoal slurry for
      managing drug overdoses.

PMID- 20795845
TI  - Analysis of linezolid-associated hematologic toxicities in a large veterans
      affairs medical center.
AB  - STUDY OBJECTIVES: To characterize linezolid-associated hematologic toxicities in
      a large clinical practice setting and to examine the variables associated with
      development of hematologic toxicities; a secondary objective was to characterize
      other linezolid-associated toxicities in this population. DESIGN: Retrospective
      medical record review. SETTING: Academic Veterans Affairs medical center.
      PATIENTS: Four hundred forty-four patients (mean age 63.7 yrs) who received 544
      courses of linezolid from 2004-2007. MEASUREMENTS AND MAIN RESULTS: Pertinent
      laboratory data were collected at baseline, periodically throughout each
      linezolid course, and up to 31 days after discontinuation. The frequencies of
      grade 1-2 and grade 3-4 thrombocytopenia were 7.6% and 5.2%, respectively. Grade
      3-4 anemia developed in 18.8% of courses; each of the patients had baseline grade
      1-2 anemia. Linezolid was discontinued because of toxicity in 35 (6.4%) of the
      544 courses. Independent variables associated with grade 3-4 thrombocytopenia
      included a baseline hemoglobin level of less than 10.5 g/dl, presence of
      immunosuppression, and a baseline platelet count of 50-99.9 x 10(3)/mm(3).
      Independent variables associated with development of grade 3-4 anemia included
      presence of a cardiovascular condition, urologic condition, immunosuppression,
      and a baseline platelet count of 50-99.9 x 10(3)/mm(3). Other toxicities reported
      with linezolid included diarrhea (6.6% of courses), followed by nausea (4.4%) and
      vomiting (4.0%). CONCLUSION: The overall rates of thrombocytopenia and anemia for
      patients receiving linezolid were found to be higher than those in phase III
      clinical trials. This may be attributable in part to the inclusion of patients
      with comorbidities that were exclusion criteria in the phase III clinical trials.
      Clinicians should be aware of variables associated with the development of severe
      thrombocytopenia and anemia in patients receiving linezolid so that they may
      predict which patients are likely to develop these toxicities and consider
      potential alternative therapies in those patients.

PMID- 20795846
TI  - Dronedarone: a new antiarrhythmic agent.
AB  - Dronedarone is an antiarrhythmic agent recently approved by the United States
      Food and Drug Administration for the reduction of cardiovascular-related
      hospitalizations in patients with paroxysmal or persistent atrial fibrillation or
      atrial flutter. The drug is a derivative of amiodarone and has been modified to
      reduce the organ toxicities frequently encountered with amiodarone. Dronedarone
      exerts its antiarrhythmic effects through multichannel blockade of the sodium,
      potassium, and calcium channels and also possesses antiadrenergic activity,
      thereby exhibiting pharmacologic effects of all four Vaughan Williams classes of
      antiarrhythmics. The efficacy of dronedarone for the maintenance of sinus rhythm,
      ventricular rate control, and reduction in cardiovascular-related
      hospitalizations has been demonstrated in several randomized, placebo-controlled
      trials. Although a high rate of gastrointestinal events (e.g., nausea, vomiting,
      and diarrhea) has been associated with dronedarone, more serious adverse events
      such as thyroid, liver, or pulmonary toxicities have not been observed. Because
      of a possible increase in mortality, dronedarone should be avoided in patients
      with New York Heart Association class IV or II-III heart failure with a recent
      decompensation. Given the efficacy and safety data currently available,
      dronedarone represents a reasonable alternative for maintenance of sinus rhythm
      in appropriately selected patients.

PMID- 20795847
TI  - Treatment options for multiple sclerosis: current and emerging therapies.
AB  - Multiple sclerosis is a chronic autoimmune disease affecting the central nervous
      system, more specifically, the myelin sheath covering of nerve fibers in the
      brain and spinal cord. This disease requires lifelong disease-modifying therapy,
      and all of the currently available first-line disease-modifying agents are
      parenteral formulations only. To date, eight drugs have entered or completed
      phases II and III clinical trials, four of which are oral drugs. These include
      five immunomodulators--cladribine, fingolimod, laquinimod, teriflunomide, and
      dimethyl fumarate--and three monoclonal antibodies--alemtuzumab, daclizumab, and
      rituximab. Although comparing these new drugs with available therapies is
      difficult, they do show promise as potential first-line agents for the treatment
      of multiple sclerosis. This marks a new frontier in the treatment of this
      disease, as the advent of new oral drugs will lead to increased patient
      compliance and contribute to longer sustained symptom-free periods and less
      marked disability.

PMID- 20795848
TI  - Pharmacologic treatment for postpartum depression: a systematic review.
AB  - During the past decade, the medical community has expressed a growing concern
      over the high prevalence of postpartum depression and the tragic repercussions of
      untreated illness. However, many questions persist about the pathogenesis of
      postpartum depression, the natural course of the illness, and the safety and
      effectiveness of available treatments. To summarize the data on pharmacologic
      treatments for postpartum depression, we performed a systematic review of four
      major databases to identify original research published from 1960-September 2009
      that featured pharmacologic treatments for depression detected in women during
      the 12 months after delivery. Pharmacologic treatments included prescription
      drugs (antidepressants and hormones), herbal remedies, and dietary supplements.
      Case reports, studies examining the prevention of postpartum depression, and
      those including diagnosed episodes of depression preceding the postpartum period
      (i.e., antepartum onset) were excluded. Treatment randomization or the presence
      of a control group was not required for inclusion in this review. Fourteen
      investigations met inclusion criteria. Nine studies examined the effects of
      prescription antidepressants, two investigated hormones, and three featured omega
      3 fatty acid supplementation. Significant heterogeneity was evident in study
      design and prevented a pooled quantitative analysis of treatment effects. The
      power of most investigations was limited, and numerous confounding biases were
      evident. Therapeutic effects were documented for prescription antidepressants and
      hormone supplementation (estrogen derivatives). Tolerability of the interventions
      in depressed mothers and breastfed infants was not well described. The
      effectiveness of omega-3 fatty acids was not evident in postpartum depression
      trials, although significant limitations in study methodology were apparent.
      Postpartum depression is a common and serious medical problem, but most cases go
      undetected and untreated. The need to identify safe, effective, and convenient
      treatments for postpartum depression is urgent, but the current state of the
      medical literature describing pharmacologic interventions is not impressive.
      Preliminary evidence documenting the effectiveness of serotonergic
      antidepressants and hormone supplementation should serve as an impetus for
      rigorous controlled investigations in the future.

PMID- 20795849
TI  - Adjunctive use of atypical antipsychotics for treatment-resistant generalized
      anxiety disorder.
AB  - Generalized anxiety disorder (GAD) is a common, chronic mental illness that has a
      significant burden on the patient's quality of life. Treatment for GAD routinely
      consists of monotherapy with a proven anxiolytic such as an antidepressant or
      benzodiazepine, but many patients do not respond fully to these drugs, and
      additional treatment may be needed. Therefore, we reviewed the safety and
      efficacy of atypical antipsychotics as adjunct therapy to standard GAD
      pharmacotherapy in patients deemed treatment resistant. We performed a literature
      search of the MEDLINE database for English-language articles published from
      January 1966-May 2009. Identified articles were evaluated, and only open-label
      trials and randomized controlled trials (RCTs) were included in the review.
      Relevant references from the articles were also evaluated. Only a few reports of
      large-scale RCTs that assessed an atypical antipsychotic for treatment-resistant
      GAD have been published. Articles were found for five of the eight currently
      available atypical antipsychotics, but not for asenapine, clozapine, and
      paliperidone. Several open-label trials and smaller RCTs support the need for
      further evaluation of aripiprazole and quetiapine for treatment-refractory GAD,
      although one quetiapine trial demonstrated negative results. There is disparate
      data for risperidone, with one open-label trial and one small RCT showing
      positive results and one large RCT showing negative results. One open-label trial
      of ziprasidone and one RCT of olanzapine both showed beneficial effects of the
      drugs. Adverse effects were specific to each agent, with weight gain being the
      most common, but many studies did not monitor systematically for lipid level,
      weight, or glucose level changes. Although data suggest efficacy regarding the
      use of atypical antipsychotics for augmentation of treatment-refractory GAD, more
      rigorous studies (large, double-blind, placebo-controlled trials) on the safety
      and efficacy of these agents are needed in order to recommend their use in
      patients with GAD.

PMID- 20795850
TI  - Insulin glargine and cancer risk: an opinion statement of the Endocrine and
      Metabolism Practice and Research Network of the American College of Clinical
      Pharmacy.
AB  - Diabetes mellitus has reached epidemic proportions worldwide, eliciting extensive
      research on both the disease process and its treatment. Regardless of diabetes
      type, the progressive nature of the disease makes insulin the long-term mainstay
      of diabetes management. Recently, the insulin analog glargine was reported in
      several epidemiologic studies to be associated with an increased risk of cancer.
      Inconsistent study results and media attention have caused much angst and concern
      to health care professionals and the general population. A clear understanding of
      the current evidence is needed to adequately develop a patient-oriented
      risk:benefit assessment. Members of the Endocrine and Metabolism Practice and
      Research Network of the American College of Clinical Pharmacy evaluated available
      evidence to provide guidance and discussion on the risk of cancer with insulin
      glargine use. We believe the current link between insulin glargine and cancer is
      tenuous but merits further evaluation. An independent analysis of all available
      glargine clinical trial data should be performed, and a vigorous postmarketing
      safety study of glargine should be conducted. Until more substantial data are
      available, however, neither the choice of initial insulin therapy nor insulin
      maintenance regimens should be influenced by the current information linking
      insulin glargine to cancer.

PMID- 20795851
TI  - The essential research curriculum for doctor of pharmacy degree programs.
AB  - In 2008, the American College of Clinical Pharmacy appointed the Task Force on
      Research in the Professional Curriculum to review and make recommendations on the
      essential research curriculum that should be part of doctor of pharmacy
      (Pharm.D.) degree programs. The essential research curriculum provides all
      students with critical and analytical thinking and lifelong learning skills,
      which will apply to current and future practice and stimulate some students to
      pursue a career in this field. Eight key curricular competencies are as follows:
      identifying relevant problems and gaps in pharmacotherapeutic knowledge;
      generating a research hypothesis; designing a study to test the hypothesis;
      analyzing data results using appropriate statistical tests; interpreting and
      applying the results of a research study to practice; effectively communicating
      research and clinical findings to pharmacy, medical, and basic science audiences;
      interpreting and effectively communicating research and clinical findings to
      patients and caregivers; and applying regulatory and ethical principles when
      conducting research or using research results. Faculty are encouraged to use
      research-related examples across the curriculum in nonresearch courses and to
      employ interactive teaching methods to promote student engagement. Examples of
      successful strategies used by Pharm.D. degree programs to integrate research
      content into the curriculum are provided. Current pharmacy school curricula allow
      variable amounts of time for instructional content in research, which may or may
      not include hands-on experiences for students to develop research-related skills.
      Therefore, an important opportunity exists for schools to incorporate the
      essential research curriculum. Despite the challenges of implementing these
      recommendations, the essential research curriculum will position pharmacy school
      graduates to understand the importance of research and its applications to
      practice. This perspective is provided as an aid and a challenge to those in
      leadership and teaching positions within schools and colleges of pharmacy.

PMID- 20795852
TI  - Bacterial wilt resistance in tomato, pepper, and eggplant: genetic resources
      respond to diverse strains in the Ralstonia solanacearum species complex.
AB  - Bacterial wilt, caused by strains belonging to the Ralstonia solanacearum species
      complex, inflicts severe economic losses in many crops worldwide. Host resistance
      remains the most effective control strategy against this disease. However, wilt
      resistance is often overcome due to the considerable variation among pathogen
      strains. To help breeders circumvent this problem, we assembled a worldwide
      collection of 30 accessions of tomato, eggplant and pepper (Core-TEP), most of
      which are commonly used as sources of resistance to R. solanacearum or for
      mapping quantitative trait loci. The Core-TEP lines were challenged with a core
      collection of 12 pathogen strains (Core-Rs2) representing the phylogenetic
      diversity of R. solanacearum. We observed six interaction phenotypes, from highly
      susceptible to highly resistant. Intermediate phenotypes resulted from the
      plants' ability to tolerate latent infections (i.e., bacterial colonization of
      vascular elements with limited or no wilting). The Core-Rs2 strains partitioned
      into three pathotypes on pepper accessions, five on tomato, and six on eggplant.
      A "pathoprofile" concept was developed to characterize the strain clusters, which
      displayed six virulence patterns on the whole set of Core-TEP host accessions.
      Neither pathotypes nor pathoprofiles were phylotype specific. Pathoprofiles with
      high aggressiveness were mainly found in strains from phylotypes I, IIB, and III.
      One pathoprofile included a strain that overcame almost all resistance sources.

PMID- 20795853
TI  - Sexual reproduction and gene flow in the pine pathogen Dothistroma septosporum in
      British Columbia.
AB  - Dothistroma septosporum has caused a serious needle blight epidemic in the
      lodgepole pine forests in northwest British Columbia over the past several years.
      Although ascocarps had been observed in British Columbia, nothing was known about
      the contribution of sexual reproduction, gene flow and long-distance dispersal to
      the epidemic. Amplified fragment length polymorphism and mating-type markers in
      19 sites were used to generate population and reproductive data. Overall,
      evidence suggests a mixed mode of reproduction. Haplotypic diversity was high,
      with 79 unique and 56 shared haplotypes (possible clones) identified from 192
      fungal isolates. Overall, mating-type segregation did not differ significantly
      from 1:1; however, random mating was rejected in most populations in the index of
      association and parsimony tree-length permutation analyses using the full data
      set and, when using clone-corrected data sets, more of the smaller populations
      showed random mating. Two of the smaller populations consistently showed random
      mating for both tests using both clone-corrected and noncorrected data. High gene
      flow is suggested by no differentiation between 14 of the 19 sites, several of
      which came from young plantations where the pathogen was not likely present prior
      to the current outbreak. The remaining five sites showed some level of
      divergence, possibly due to historic separation and endemic pathogen populations.
      Results indicate a high evolutionary potential and long-distance dispersal in
      this pathogen, important to consider in future forest management.

PMID- 20795854
TI  - Identification of regional climatic conditions favorable for development of
      European canker of apple.
AB  - Months of the year with high risk of European canker (Neonectria galligena)
      development in areas of the United States, Chile, England, and Northern Ireland
      were determined from published data. Moving-window analysis of long-term climatic
      data was used to classify disease risk in these areas in relation to rainfall and
      temperature conditions using the degree of agreement statistic. Greatest
      agreement occurred when it both rained on >30% of days/month and there was an
      average of >8 h/day with temperature of 11 to 16 degrees C. When these thresholds
      were applied in eight validation areas in New Zealand, Australia, the United
      States, The Netherlands, and Denmark, areas with reported higher risk of disease
      tended to be areas where the thresholds were exceeded more often and by greater
      amounts. Areas at higher latitudes (>52 degrees ) with frequent summer rainfall
      appeared to be most prone to European canker, including the fruit rot phase of
      the disease, probably because summer temperatures were more favorable than at
      lower latitudes. The climatic thresholds derived for European canker could be
      useful for studies of disease establishment risk, surveillance, eradication,
      climate change impact assessment, and, possibly, for disease risk forecasting.
      The methods used in this study allowed conditions favorable for disease
      development to be identified even though quantitative regional disease data were
      lacking, and they could be useful for similar geoclimatic studies of other
      diseases.

PMID- 20795855
TI  - TaDAD2, a negative regulator of programmed cell death, is important for the
      interaction between wheat and the stripe rust fungus.
AB  - Defender against cell death (DAD) genes are known to function as negative
      regulators of cell death in animals. In plants, DAD orthologs are conserved but
      their role in cell death regulation is not well understood. Here, we report the
      characterization of the TaDAD2 gene in wheat. The predicted amino acid sequence
      of TaDAD2 contains typical structural features of DAD proteins, including a
      signal peptide, three transmembrane regions, and a subunit of
      oligosaccharyltransferase. Transcripts of TaDAD2 were detected in wheat leaves,
      culms, roots, florets, and spikelets. The expression level of TaDAD2 was reduced
      in the initial contact with the stripe rust fungus, subsequently induced and
      peaked at 18 h postinoculation (hpi), gradually reduced at 24 to 48 hpi, and
      restored to control level at 72 to 120 hpi. In addition, TaDAD2 exhibited
      positive transcriptional responses to abiotic stresses after the initial
      reduction at 1 hpi. Overexpression of TaDAD2 in tobacco leaves inhibited cell
      death. Furthermore, knocking down TaDAD2 expression by virus-induced gene
      silencing enhanced the susceptibility of wheat cv. Suwon11 to avirulent race
      CYR23 and reduced necrotic area at the infection sites. These results indicate
      that TaDAD2 may function as a suppressor of cell death in the early stages of
      wheat-stripe rust fungus interaction. However, it is dispensable for or plays an
      opposite role in hypersensitive response or cell death triggered by an avirulent
      race of stripe rust fungus at late-infection stages.

PMID- 20795856
TI  - Mutations in the P3 protein of Soybean mosaic virus G2 isolates determine
      virulence on Rsv4-genotype soybean.
AB  - Two Soybean mosaic virus (SMV) G2 isolates, L and L-RB, sharing high-sequence
      similarly but differing in ability to break Rsv4-mediated resistance in soybean,
      were investigated. Infectious clones corresponding to these two isolates and
      their chimeric clones resulting from swapping different regions of genomic cDNA
      between L and L-RB were constructed. Only L-RB or chimeras containing the middle
      fragment of L-RB cDNA showed virulence on Rsv4-genotype soybean. Sequence
      comparison analysis revealed that the middle genomic region of L and L-RB encodes
      four different amino acids. Point mutagenesis demonstrated that a single amino
      acid substitution (Q1033K) in the P3 protein determined virulence toward Rsv4
      resistance. In addition, six new SMV Rsv4 resistance-breaking isolates, variants
      of the second passage on Williams 82 infected with the chimeras or mutants
      noninfectious on soybean carrying Rsv4, were obtained. Sequencing data indicated
      that these new isolates contain either the Q1033K mutation or a new substitution
      (G1054R) in P3. Site-directed mutagenesis confirmed the virulence role of the
      G1054R mutation on Rsv4-genotype soybean. Taken together, these data suggest that
      P3 of the SMV G2 strain is an avirulent determinant for Rsv4 and one single
      nucleotide mutation in P3 may be sufficient to compromise its elicitor function.

PMID- 20795857
TI  - A novel transcriptional factor important for pathogenesis and ascosporogenesis in
      Fusarium graminearum.
AB  - Fusarium head blight or scab caused by Fusarium graminearum is an important
      disease of wheat and barley. The pathogen not only causes severe yield losses but
      also contaminates infested grains with mycotoxins. In a previous study, we
      identified several pathogenicity mutants by random insertional mutagenesis. One
      of these mutants was disrupted in the ZIF1 gene, which encodes a b-ZIP
      transcription factor unique to filamentous ascomycetes. The Deltazif1 mutant
      generated by gene replacement was significantly reduced in deoxynivalenol (DON)
      production and virulence on flowering wheat heads. It was defective in spreading
      from inoculated florets to the rachis and other spikelets. Deletion of the ZIF1
      ortholog MoZIF1 in the rice blast fungus also caused reductions in virulence and
      in invasive growth. In addition, the Deltazif1 mutant is defective in sexual
      reproduction. Although it had normal male fertility, when selfed or mated as the
      female in outcrosess, the Deltazif1 mutant produced small, pigmented perithecia
      that were sterile (lack of asci and ascospores), suggesting a female-specific
      role for ZIF1 during fertilization or ascus development. Similar female-specific
      defects in sexual reproduction were observed in the DeltaMozif1 mutant. When
      mated as the female, the DeltaMozif1 perithecia failed to develop long necks and
      asci or ascospores. The ZIF1 gene is well conserved in filamentous ascomycetes,
      particularly in the b-ZIP domain, which is essential for its function. Expression
      of ZIF1 in Magnaporthe oryzae complemented the defects of the DeltaMozif1 mutant.
      These results indicate that this b-ZIP transcription factor is functionally
      conserved in these two fungal pathogens for plant infection and sexual
      reproduction.

PMID- 20795858
TI  - Topical cyclosporine in thyroid orbitopathy-related dry eye: clinical findings,
      conjunctival epithelial apoptosis, and MMP-9 expression.
AB  - OBJECTIVES: To evaluate the effects of topical cyclosporine A (CsA) 0.05%
      (Restasis) on the signs and symptoms of dry eye, on apoptosis, and on MMP-9
      expression in conjunctiva epithelial cells in thyroid orbitopathy (TO)-related
      dry eye patients. METHODS: Prospective, clinical study. Twenty-four eyes of 12
      consecutive TO patients with dry eye findings instilled CsA twice daily for 2
      months. Ocular surface disease index, Schirmer tear test, tear breakup time
      (TBUT), conjunctival apoptosis index, and conjunctival MMP-9 expression were
      evaluated before and after 2 months treatment. Conjunctival biopsies were
      harvested from all eyes at baseline and after 2 months treatment. Apoptosis was
      detected by the terminal deoxynucleotidyl transferase-mediated dUTP-nick end
      labeling (TUNEL) assay. MMP-9 expression was determined by immunohistochemistry.
      RESULTS: After 2 months of topical CsA treatment, the mean OSDI score was
      significantly decreased from 58.08 +/- 6.28 to 36.41 +/- 11.75 (P = 0.001). At
      baseline, the mean Schirmer tear test score was 8.92 +/- 5.52 mm. It was
      increased to 11.25 +/- 4.71 mm after treatment (P > 0.05). The mean TBUT
      increased significantly from 3.92 +/- 2.18 sec to 9.16 +/- 3.34 sec (P = 0.001).
      The mean percentage of apoptosis index at baseline was 72.10 +/- 35.82%. This was
      significantly decreased to 53.29 +/- 34.46% after treatment (P = 0.008). The mean
      percentage of MMP-9 expression of the conjunctival epithelial cells was
      significantly decreased from 48.12 +/- 28.58% to 26.66 +/- 25.13% following
      treatment (P = 0.005). CONCLUSIONS: Topical CsA treatment appears to improve the
      signs and symptoms of dry eye and inhibits apoptosis and MMP-9 expression in
      conjunctival epithelial cells in TO-related dry eye patients after 2 months of
      treatment.

PMID- 20795859
TI  - Confirmation of changes in human meibum lipid infrared spectra with age using
      principal component analysis.
AB  - PURPOSE: Changes in the phase transition temperatures and conformation of human
      meibum lipid with age and meibomian gland dysfunction (MGD) have been quantified.
      Less than 1% of the infrared spectral range was used in the previous studies to
      demonstrate differences. In this study, the remaining 99% of the spectral
      frequencies were analyzed to gain insight into changes that occur in meibum with
      age. METHODS: Infrared spectra of meibum from 27 normal donors were acquired.
      Principal component analysis (PCA) was used to quantify the variance between the
      spectra. RESULTS: PCA was applied to a set of training spectra of human meibum to
      predict the age of meibum donors. The plot of predicted age versus actual age was
      linear, p < 0.001 with a slope of 1.00 and r = 0.909. This indicates that changes
      in constituents of the meibum spectra (eigenvectors) were due to age-related
      compositional differences. Eigenvector 1 accounted for 92% of the variance
      observed among all of the meibum spectra. The spectral features of the two major
      eigenvectors indicate that with increasing age, the meibum contains more wax,
      double bonds and terminal CH(3) groups, and is less ordered. The environment of
      the carbonyl band becomes less polar with increasing age. These results are
      similar to those obtained for human sebum. CONCLUSIONS: PCA is an excellent
      chemometric algorithm that may be used to characterize MGD and age-related
      changes in human meibum. The eigenvectors that define the variations in the
      spectra provide clues to the compositional changes that occur in meibum with age.

PMID- 20795860
TI  - Assessment of Streptococcus pneumoniae capsule in conjunctivitis and keratitis in
      vivo neuraminidase activity increases in nonencapsulated pneumococci following
      conjunctival infection.
AB  - PURPOSE: The pneumococcal capsule is required for pathogenesis in systemic
      infections, yet reports show most conjunctivitis outbreaks are caused by
      nonencapsulated pneumococci, while keratitis infections are caused by
      encapsulated strains. This study aims to determine the effect of capsule in
      pneumococcal keratitis and conjunctivitis in rabbit models of infection. METHODS:
      A capsule-deficient isogenic mutant was created using homologous transformation.
      Parent and mutant strains were injected within the upper bulbar conjunctiva
      (conjunctivitis) or into the corneal stroma (keratitis) of New Zealand white
      rabbits. Clinical examinations were performed 24 and 48 hr post-infection at
      which time corneas or conjunctivae were removed, homogenized, and plated to
      determine the recovered bacterial load. Whole eyes were removed for histological
      examination. The neuraminidase activity was determined following in vitro and in
      vivo growth. RESULTS: There were no significant differences in clinical scores
      between the eyes infected with the parent or mutant for either infection, nor was
      there a difference in the amount of bacteria recovered from the cornea. In the
      conjunctivae, however, the mutant strain was cleared by the host faster than the
      parent strain. Histological examination showed slightly more infiltrating
      polymorphonuclear leukocytes (PMN) and macrophages in the conjunctivae infected
      with the parent strain. The neuraminidase activity of both strains was not
      significantly different when the strains were grown in vitro. However, the
      neuraminidase activity of the parent was significantly less than that of the
      mutant at 3 and 12 hr post conjunctival infection. CONCLUSIONS: Although more
      outbreaks of pneumococcal conjunctivitis are tied to nonencapsulated S.
      pneumoniae strains, this study showed that an encapsulated strain was capable of
      establishing conjunctivitis in a rabbit injection model and survive attack by the
      host immune system longer than its nonencapsulated isogenic mutant. Nonetheless,
      the nonencapsulated pneumococci had an increased neuraminidase activity level in
      vivo when compared to the parent strain.

PMID- 20795861
TI  - MMP-7 knock-in corneal fibroblast cell lines secrete MMP-7 with proteolytic
      activity towards collagen XVIII.
AB  - PURPOSE: To determine whether matrix metalloproteinase-7 (MMP-7) that is stably
      overexpressed by mouse corneal fibroblast cell lines exhibits proteolytic
      activity against the NC1 fragment of collagen XVIII. METHODS: Corneal fibroblasts
      isolated from MMP-7 knockout (7ko) mice were subjected to SV40 T-antigen
      immortalization and stably transfected with a bicistronic retroviral vector
      encoding green fluorescence protein and active MMP-7. The resulting MMP-7 knock
      in fibroblasts (7ko-MMP-7 cells) were isolated and enriched by fluorescence
      activated cell sorting (FACS). Culture media samples from 7ko and 7ko-MMP-7 cells
      were then incubated with the recombinant NC1 fragment of collagen XVIII, and NC1
      degradation was monitored by immunoblotting. RESULTS: Immunoblot analysis
      revealed that MMP-7 was present in lysates and culture media from 7ko-MMP-7
      fibroblasts, but not media from immortalized 7ko fibroblasts. Importantly, lower
      amounts of the NC1 fragment were present in in vitro enzymatic reaction mixtures
      containing concentrated 7ko-MMP-7 media than in those containing concentrated 7ko
      media. CONCLUSION: Immortalized fibroblasts stably transfected with MMP-7 secrete
      active MMP-7 with proteolytic activity towards the NC1 fragment of collagen
      XVIII.

PMID- 20795862
TI  - Urokinase down-regulation by aprotinin in rabbit corneal cells after
      photorefractive keratectomy.
AB  - PURPOSE: To examine the effect of aprotinin eye drops on urokinase-type
      plasminogen activator (uPA) gene expression in rabbit corneal cells during wound
      healing after photorefractive keratectomy (PRK). METHODS: Both eyes of 22 rabbits
      were subjected to PRK. One eye of each rabbit was treated with antibiotic eye
      drops five times while the contralateral eye was treated at the same time with
      antibiotic eye drops and a serine protease inhibitor. The animals were sacrificed
      at different time frames, and 2-4 rabbits were used for each time point. Half of
      each cornea was used for the determination of the amount of uPA mRNA after
      reverse transcription and real-time quantitative polymerase chain reaction, while
      frozen sections were prepared from the other halves for in situ zymography to
      detect uPA activity. RESULTS: The level of uPA mRNA in corneal cells was markedly
      increased in corneal samples obtained hours after PRK. The time-dependent up
      regulation of uPA mRNA was strongly dependent on the diameter of the area from
      which the epithelial cells were removed before the surgery. Independently of the
      time scale of uPA up-regulation, application of eye drops containing aprotinin
      significantly diminished the uPA expression. In situ zymography confirmed that
      aprotinin has also decreased overall uPA activity. CONCLUSIONS: Aprotinin down
      regulates uPA gene expression in corneal cells during the wound-healing phase
      after PRK.

PMID- 20795863
TI  - Genomic profiling of miRNAs in two human lens cell lines.
AB  - PURPOSE: Many miRNAs are expressed in a developmentally regulated and tissue
      specific manner making them crucial for tissue development in a structure such as
      the eye. Since miRNA target function studies for the eye will need to be
      performed in ocular tissue culture cells, it is important to profile them for
      miRNA expression. Two commonly used human lens epithelial cell lines, HLE-B3 and
      SRA01/04, were profiled for miRNA. MATERIALS AND METHODS: We performed miRNA
      profiling of two commonly used lens epithelial cell lines, HLE-B3 and SRA01/04.
      The differential expression levels detected for miR-184 and miR-31 were confirmed
      by qRT-PCR and the function of a predicted miR-184 target binding site was
      validated in-vitro. RESULTS: We found that four miRNAs-miR-31, miR-124, miR-184,
      and miR-222-were differentially expressed between the two cell lines. We show
      that miR-184 binds to BIN3 3' UTR and while BIN3 mRNA expression was equal in
      both cell lines, the protein expression was inversely correlated with miR-184
      expression. CONCLUSION: The differences observed with respect to miRNA expression
      between two different lens epithelial cell lines were minimal. Still, caution
      will need to be exercised when choosing one cell line over another because of the
      expression differences for some miRNAs. Our results also suggest that miR-184 may
      regulate lens BIN3 expression in lens by a miRNA-mediated translational
      repression mechanism.

PMID- 20795864
TI  - Duration of anesthesia affects intraocular pressure, but not outflow facility in
      mice.
AB  - PURPOSE: The study of aqueous humor dynamics (AHD) in mice is becoming more
      prevalent as more strains with elevated intraocular pressure (IOP) are developed.
      High IOP is usually associated with reduced outflow facility making this one of
      the more important AHD parameters to evaluate. Ocular measurements in mice
      require anesthesia that has profound effects on IOP but unknown effects on
      outflow facility. This study evaluates the effects of anesthesia duration and
      latanoprost treatment on outflow facility and IOP in BALB/c mice. METHODS: IOPs
      were measured in conscious and anesthetized mice by tonometry. Outflow facility
      was evaluated in 15-min intervals at three pressure levels over two 45-min
      periods. Comparisons were made between latanoprost-treated eyes and untreated
      contralateral eyes. To determine the effect of anesthesia duration on IOP, a
      microneedle method was used to follow IOP for 120 min in separate mice. RESULTS:
      IOP was 9.7 +/- 0.3 mmHg (mean +/- SEM) in conscious mice and 7.1 +/- 0.02 within
      10 min of anesthesia initiation (p < 0.01). IOP changed significantly between but
      not within assessment periods. IOP at 75 min was significantly (p = 0.004)
      reduced compared to IOP at 15 min after initial anesthesia. In control eyes,
      outflow facility did not change between the two 45-min assessment periods during
      the 120 min test (p = 0.80). In latanoprost-treated eyes, outflow facility
      increased compared with control eyes during both assessment periods (p = 0.03). A
      test of filters in series with known resistance found that the method was
      sensitive enough to detect a change in outflow facility of 0.001 microl/min/mmHg.
      CONCLUSIONS: Administration of ketamine/xylazine anesthesia for 120 min did not
      alter outflow facility or lessen the effect of latanoprost on outflow facility in
      mice as determined by a new analysis system. Accurate IOP measurements must be
      made within minutes of anesthesia administration but outflow facility
      measurements can be made with less haste.

PMID- 20795865
TI  - Distribution of amyloid precursor protein and amyloid-beta in ocular hypertensive
      C57BL/6 mouse eyes.
AB  - PURPOSE: Amyloid precursor protein (APP) and amyloid-beta (Abeta) appear to
      participate in the pathophysiology of retinal ganglion cell (RGC) death in
      glaucoma. We, therefore, determined the distribution of APP and Abeta in the
      retinas of C57BL/6 mice after induction of chronic ocular hypertension. METHODS:
      Ocular hypertension was induced in one eye of three-month-old C57BL/6 mice by
      injection of hypertonic saline into episcleral veins. After 6 weeks of documented
      elevated intraocular pressure (IOP), retinas were fixed with 4% paraformaldehyde
      and processed for immunohistochemistry with antibodies including a polyclonal
      antibody to the C-terminus of Abeta 40 (Novartis 17-40/23) and a polyclonal
      antibody to the APP ectodomain (Novartis 474). Distribution and semiquantitative
      expression of APP and Abeta immunolabeling in ocular hypertensive and control
      retinas were graded in a masked fashion and compared. RESULTS: APP and Abeta
      immunoreactivity was found in the pia/dura, optic nerve (ON), and RGC layer of
      ocular hypertensive retinas, whereas APP and Abeta immunoreactivity in the
      contralateral control eyes was detected only in the pia/dura. Comparison of
      ocular hypertensive and control eyes for Abeta immunolabeling was significant in
      the ON and RGC layer (p < 0.05) whereas no significant difference was found when
      compared for APP staining. CONCLUSIONS: High Abeta and APP levels were seen in
      ocular hypertensive retinas, probably due to abnormal APP-splicing in the
      presence of elevated IOP.

PMID- 20795866
TI  - Influence of non-toxic doses of bevacizumab and ranibizumab on endothelial
      functions and inhibition of angiogenesis.
AB  - PURPOSE: Ranibizumab (Lucentis) is an antibody fragment developed against all
      fragments of vascular endothelial growth factor (VEGF) that was approved by the
      FDA for treating age-related macular degeneration (AMD). Bevacizumab, a full
      length anti-VEGF antibody approved for use in colon cancer, is non-FDA approved
      at this time but it is widely used for treating AMD. The purpose of this study
      was to compare the influence of Bevacizumab and Ranibizumab on angiogenesis in an
      in vitro model. METHODS: A model consisting of H5V cells derived from murine
      hearts capillary endothelial cells (ECs) was used. The H5V cells were treated
      with three concentrations of Bevacizumab and Ranibizumab (0.125 mg/mL, 0.25
      mg/mL, and 0.50 mg/mL) for 24 hr before all experiments. The effects of
      Bevacizumab and Ranibizumab on EC proliferation were compared by 3H-thymidine
      incorporation essay. Toxic effects and the safety of each drug in clinical
      concentrations were assessed by annexin 5 staining. The effects of the drugs on
      ECs functions were assessed by their ability to adhere to fibronectin and by
      evaluation of the cells' tube formation capacity on matrigel. RESULTS: Both
      Bevacizumab and Ranibizumab equally suppressed the adhesive properties of ECs to
      fibronectin, and similarly inhibited ECs' proliferation capacity in a dose
      dependent manner. Both Bevacizumab and Ranibizumab inhibited the ECs' tube
      formation capacity on matrigel, and were equally safe. CONCLUSIONS: Ranibizumab
      and Bevacizumab at low, non-toxic doses similarly inhibit several properties of
      the angiogenesis process. Inhibition of ECs adhesion to fibronectin and tube
      formation capacity does not seem to be directly related to the anti-angiogenic
      effects as indicated by inhibition of VEGF. Further studies for delineating the
      exact mechanism of action of Ranibizumab and Bevacizumab in angiogenesis are
      warranted.

PMID- 20795867
TI  - Dietary deficiency of vitamin E aggravates retinal ganglion cell death in
      experimental glaucoma of rats.
AB  - PURPOSE: Investigate the effect of dietary vitamin E (Vit E) on the retinas of a
      rat model of induced glaucoma, in which surgically induced elevation of
      intraocular pressure (IOP) is associated with an increase in reactive oxygen
      species. METHODS: Rats were fed a standard chow, Vit E-supplemented diet, or Vit
      E-deficient diet and subjected to surgically induced IOP elevation (or sham
      surgery) for five weeks. The retinal ganglion cells (RGCs) were subjected to
      retrograde fluorescent tracer labeling. RESULTS: The mean number of RGCs of rats
      on the standard chow, Vit E-supplemented diet, and Vit E-deficient diet were
      79.6%, 78.6%, and 71.3% of controls, respectively. Lipid peroxidation of the
      retinas of rats given a Vit E-deficient diet were significantly higher after IOP
      elevation for three days (14.42 +/- 0.25 microM, P = 0.016) and five weeks (10.46
      +/- 0.11 microM, p = 0.042), compared to rats given standard chow (11.37 +/- 0.31
      microM; 8.95 +/- 0.16 microM). Compared with rats given standard chow, rats given
      a Vit E-deficient diet had significantly elevated concentrations of glutathione
      (p = 0.032), but no significant differences in the levels of total superoxide
      dismutase (SOD), Cu/Zn SOD, or catalase activities three days after IOP
      elevation. CONCLUSIONS: Rats fed a Vit E-deficient diet with surgically induced
      IOP elevation experience significantly more RGC death than rats fed a normal
      diet. This phenomenon may be related to the increased level of lipid peroxidation
      in Vit E-deficient rats.

PMID- 20795868
TI  - Retinal vascular fractal dimension measurement and its influence from imaging
      variation: results of two segmentation methods.
AB  - AIM: To assess the influences of imaging variation (different photographic angle)
      on the measurement of retinal vascular fractal dimension (D(f)), using two
      segmentation methods. MATERIALS AND METHODS: Nonlinear orthogonal projection
      segmentation (International Retinal Imaging Software-Fractal, termed IRIS
      Fractal) and curvature-based segmentation (Singapore Institute Vessel Assessment
      Fractal, termed SIVA-Fractal) methods were used to measure D(f) and were assessed
      for their reproducibility in detecting retinal vessels of 30 stereoscopic pairs
      of optic disc color images. Each pair was taken from the same eye with slightly
      different angles of incidence. Each photograph of the pairs had subtle variations
      in brightness between areas temporal and nasal to the optic disc. RESULTS:
      Intragrader reproducibility of D(f) measurement was similar (intraclass
      correlation 0.81 and 0.96, respectively) for IRIS-Fractal and SIVA-Fractal.
      Within-image pair Pearson's correlation coefficients (r) of D(f) measurements
      were moderate for both methods (0.57 and 0.48, respectively). CONCLUSIONS: Both
      nonlinear orthogonal projection and curvature-based retinal vessel segmentation
      methods were found to be sensitive to variations in image brightness, resulting
      from iris shadowing associated with different angle of photographic incidence.

PMID- 20795870
TI  - Acute pharmacological DVT prophylaxis after spinal cord injury.
AB  - A systematic review of the literature was performed to address pertinent clinical
      questions regarding deep vein thrombosis (DVT) prophylaxis in the setting of
      acute spinal cord injury (SCI). Deep vein thromboses are a common occurrence
      following SCI. Administration of low-molecular-weight heparin (LMWH) within 72 h
      of injury is recommended to minimize the occurrence of DVT. Furthermore, when
      surgical intervention is required, LMWH should be held the morning of surgery,
      and resumed within 24 h post-operatively.

PMID- 20795869
TI  - Association between gene expression profile, proliferation and metastasis in
      uveal melanoma.
AB  - PURPOSE: Uveal melanomas cluster into two molecular groups based on their gene
      expression profile. Tumors with the class 1 signature rarely metastasize, whereas
      those with the class 2 signature have a very high rate of metastasis. However,
      the biological basis for this metastatic propensity of class 2 tumors remains
      unclear. Towards such an explanation, this study was conducted to determine
      whether class 2 tumors have a higher proliferative rate than class 1 tumors.
      MATERIALS AND METHODS: The study included 28 primary uveal melanomas with
      extensive clinical, pathologic, and genetic annotation, including age, gender,
      ciliary body involvement, tumor basal diameter, thickness, cell type, gene
      expression profile, status of chromosomes 3 and 8p, aneuploidy, and clinical
      outcome. Immunopositivity for Ki-67 was determined by counting all positive
      nuclei in representative whole tumor sections. RESULTS: Ki-67 positivity was
      significantly associated with class 2 gene expression profile, loss of chromosome
      3 and increased aneuploidy (P = 0.04, P = 0.004, and P = 0.03, respectively). Ki
      67 positivity showed a borderline significant association with epithelioid cell
      type (P = 0.07). Receiver operating characteristic (ROC) analysis of Ki-67
      positivity, using the class 2 signature as an endpoint, identified a Ki-67 score
      of approximately 20 cells per high power field as the optimal cut-off point
      between low and high risk for metastasis (log rank test, P = 0.01). CONCLUSIONS:
      On average, class 2 uveal melanomas have a higher proliferative rate than class 1
      tumors. Further work is needed to determine whether loss of chromosome 3,
      increased aneuploidy, or other factors may be responsible for the increased
      proliferation.

PMID- 20795872
TI  - Microarray analysis of temperature-induced transcriptome of Streptococcus suis
      serotype 2.
AB  - Streptococcus suis serotype 2 (S. suis S2) is able to cause human infections
      ranging from superficial wounded skin infections to severe invasive infections
      such as meningitis and streptococcal toxic shock-like syndrome. During its
      infection cycle, S. suis S2 must acclimatize itself to temperature shift. Herein,
      a whole-genome DNA microarray was used to investigate the global transcriptional
      regulation of an invasive strain of S. suis S2 grown to late-exponential phase at
      29 degrees C or 40 degrees C relative to 37 degrees C. The differentially
      regulated genes that were detected included those encoding virulence factors,
      antigenic proteins, ATP-binding-cassette transporters, and proteins of unknown
      functions. Our data provided a global profile of gene transcription induced by
      temperature alteration and shed light on some unforeseen lines for further
      pathogenesis investigation.

PMID- 20795871
TI  - High prevalence of bla(CTX-M) extended spectrum beta-lactamase genes in
      Klebsiella pneumoniae isolates from a tertiary care hospital: first report of
      bla(SHV-12), bla(SHV-31), bla(SHV-38), and bla(CTX-M-15) in Brazil.
AB  - The aim of this study was to investigate the presence and prevalence of bla(TEM),
      bla(SHV), and bla(CTX-M) and bla(GES)-like genes, responsible for extended
      spectrum beta-lactamases (ESBLs) production in clinical isolates of Klebsiella
      pneumoniae collected from a Brazilian tertiary care hospital. Sixty-five ESBL
      producing K. pneumoniae isolates, collected between 2005 and 2007, were screened
      by polymerase chain reaction (PCR). Identification of bla genes was achieved by
      sequencing. Genotyping of ESBL producing K. pneumoniae was performed by the
      enterobacterial repetitive intergenic consensus-PCR with cluster analysis by the
      Dice coefficient. The presence of genes encoding ESBLs was confirmed in 59/65
      (90.8%) isolates, comprising 20 bla(CTX-M-2), 14 bla(CTX-M-59), 12 bla(CTX-M-15),
      9 bla(SHV-12), 1 bla(SHV-2), 1 bla(SHV-2a), 1 bla(SHV-5), and 1 bla(SHV-31)
      genes. The ESBL genes bla(SHV-12), bla(SHV-31), and bla(CTX-M-15), and the
      chromosome-encoded SHV-type beta-lactamase capable of hydrolyzing imipenem were
      detected in Brazil for the first time. The analysis of the enterobacterial
      repetitive intergenic consensus-PCR band patterns revealed a high rate of
      multiclonal bla(CTX-M) carrying K. pneumoniae isolates (70.8%), suggesting that
      dissemination of encoding plasmids is likely to be the major cause of the high
      prevalence of these genes among the K. pneumoniae isolates considered in this
      study.

PMID- 20795873
TI  - The body and physiotherapy.
AB  - In recent years, physiotherapists have been increasingly interested in defining
      their professional identity. At the heart of this interest lies a fundamental
      question about the role that the body plays in defining physiotherapy practice.
      Given the importance of the body to physiotherapy, it is surprising how under
      theorized the body is in existing physiotherapy literature. With a few notable
      exceptions, the body as a philosophical/theoretical construct has been almost
      entirely bypassed by the profession. In this paper the authors argue that a
      renewed interest in the meaning given to the body by physiotherapists is timely,
      and offer a sociohistorical critique of the role the body has played in defining
      physiotherapy practice. We challenge physiotherapists' longstanding affinity with
      a biomechanical view of the body, arguing that whilst this approach may have been
      critically important in the past, it is now increasingly clear that a more
      diverse and inclusive approach to the body will be needed in the future. The
      authors explore the notion of embodiment and suggest ways in which embodiment
      theory might be applied to physiotherapy practice.

PMID- 20795874
TI  - The relationship between patient satisfaction with physical therapy care and
      global rating of change reported by patients receiving worker's compensation.
AB  - This study examined relationships between patient satisfaction with physical
      therapy care and global rating of change; 1,944 respondents completed the Medrisk
      Instrument for Measuring Patient Satisfaction with Physical Therapy Care (MR-12)
      and a nine-point Global Rating of Change Scale (GROC) following a course of
      physical therapy for a work-related musculoskeletal problem. Ninety percent of
      all respondents reported being satisfied or very satisfied with their overall
      care, whereas 70.1% of all respondents indicated they improved following
      treatment. Respondents who reported improvement had significantly higher scores
      for all measures of satisfaction (p<0.01) than did those who reported failure to
      improve; however, both of these groups had mean scores of greater than 4.0 on the
      MR-12, indicating that respondents were likely to be satisfied or very satisfied
      with care regardless of perceived change following treatment. Scores>4.0 from the
      MR-12 had high sensitivity to detect those respondents classified as "improved"
      (0.87-0.95), but low specificity to differentiate between those who were
      classified as "improved" and those who were classified as "did not improve" (0.22
      0.30). Our findings support the hypothesis that patient satisfaction with care is
      primarily independent of perceived clinical change.

PMID- 20795875
TI  - A test of an adherence-enhancing adjunct to physiotherapy steeped in the
      protection motivation theory.
AB  - The primary aim of this study was to test the effect of a Protection Motivation
      Theory (PMT)-based patient education intervention on physiotherapy patients'
      beliefs about their injury and physiotherapy, intentions to adhere,
      rehabilitation adherence, and ankle function. A secondary aim was to explore the
      relationships between the patients' injury and physiotherapy beliefs, intentions,
      adherence behaviours, and ankle function. A randomized controlled trial was
      undertaken in New Zealand; 71 people with ankle sprains were allocated to either
      PMT present video information or two control groups (non-PMT information about
      ankle sprains and no formal information) before commencing their course of
      physiotherapy. The two information groups watched a video about ankle sprains and
      physiotherapy before answering the Beliefs about Ankle Sprains and Physiotherapy
      Scale and behavioural intentions questionnaires that measured the PMT constructs.
      Adherence was assessed at each treatment and ankle function was measured before
      and after the physiotherapy program. After viewing the video, the PMT present
      information group's beliefs about severity, vulnerability, and response efficacy
      were significantly higher than the other two groups. The groups did not differ
      significantly on their self-efficacy, intentions, rehabilitation adherence, and
      post-physiotherapy program ankle function. Significant correlations existed
      between the patients' PMT-based beliefs and intentions, intentions and adherence,
      and adherence and post-physiotherapy ankle function. With the exception of self
      efficacy, the findings indicate that persuasive information grounded in PMT does
      enhance physiotherapy patients' beliefs about their injury and treatment.

PMID- 20795876
TI  - Clinical decision making in a patient with secondary hip-spine syndrome.
AB  - The prevalence of lumbar and hip pathology is on the rise; however, treatment
      outcomes have not improved, highlighting the difficulty in identifying and
      treating the correct impairments. The purpose of this case report is to describe
      the clinical decision making in the examination and treatment of an individual
      with secondary hip-spine syndrome. Our case study was a 62-year-old male with low
      back pain with concomitant right hip pain. His Oswestry Disability Index (ODI)
      was 18%, back numeric pain rating scale (NPRS) was 4/10, fear avoidance beliefs
      questionnaire (FABQ) work subscale was 0, FABQ physical activity subscale was 18,
      and patient specific functional scale (PSFS) was 7.33. Physical examination
      revealed findings consistent with secondary hip-spine syndrome. He was treated
      for four visits with joint mobilization/manipulation and strengthening exercises
      directed at the hip. At discharge, all standardized outcome measures achieved
      full resolution. Clinical decision making in the presence of lumbopelvic-hip pain
      is often difficult. Previous literature has shown that some patients with
      lumbopelvic-hip pain respond favorably to manual therapy and exercise targeting
      regions adjacent to the lumbar spine. The findings of this case report suggest
      that individuals with a primary complaint of LBP with hip impairments may benefit
      from interventions to reduce hip impairments.

PMID- 20795877
TI  - Lower limb reaction time discriminates between multiple and single fallers.
AB  - Despite research supporting its validity in predicting falls, simple reaction
      time (SRT) is not typically included in a clinical falls assessment battery
      because there is no standardised, clinically feasible testing protocol with
      published cutoff scores. This study aimed to determine whether SRT scores
      obtained using a clinically viable protocol could discriminate between multiple
      and single fallers. SRT scores were obtained from 147 participants (88 women and
      59 men) over the age of 65 years (mean 80.1 years; SD 8.4 years) who had reported
      one or more falls in the previous 12 months. Forty-eight single and 99 multiple
      fallers were recruited from the subacute public hospital sector. SRT scores
      significantly discriminated between faller groups (Wilk's lambda = 0.89, p =
      0.05), with SRT score being the dominating predictor between groups. A receiver
      operating characteristic (ROC) curve showed good diagnostic accuracy with the
      area under curve = 0.78. A cutoff score of 394.5 ms provided the best balance
      between sensitivity and specificity. Once data were dichotomized as being above
      or below this cutoff value, a binary regression analysis revealed an odds ratio
      of 7.18 (95% CI 3.3-15.6), with a positive predictive value of 84.5%. The
      clinically feasible lower limb SRT testing protocol described provided good
      discrimination between single and multiple fallers. This test may be useful in
      clinical practice to help identify older people at greater risk of future falls.

PMID- 20795878
TI  - Using interpretative phenomenological analysis to inform physiotherapy practice:
      an introduction with reference to the lived experience of cerebellar ataxia.
AB  - Qualitative research methods that focus on the lived experience of people with
      health conditions are relatively underutilised in physiotherapy research. This
      article aims to introduce interpretative phenomenological analysis (IPA), a
      research methodology oriented toward exploring and understanding the experience
      of a particular phenomenon (e.g., living with spinal cord injury or chronic pain,
      or being the carer of someone with a particular health condition). Researchers
      using IPA try to find out how people make sense of their experiences and the
      meanings they attach to them. The findings from IPA research are highly nuanced
      and offer a fine grained understanding that can be used to contextualise existing
      quantitative research, to inform understanding of novel or underresearched topics
      or, in their own right, to provoke a reappraisal of what is considered known
      about a specified phenomenon. We advocate IPA as a useful and accessible approach
      to qualitative research that can be used in the clinical setting to inform
      physiotherapy practice and the development of services from the perspective of
      individuals with particular health conditions.

PMID- 20795879
TI  - Entrainment elicits period aftereffects in Neurospora crassa.
AB  - Circadian clocks continue to oscillate in constant conditions with their own
      period (tau) and entrain to a cyclic environment by adjusting their intrinsic
      period to that of the zeitgeber. When circadian clocks are released from
      entrained to constant conditions, the tau of their initial free-run often depends
      on the nature of the prior zeitgeber. These postentrainment effects on period
      (tau-aftereffects) have predominantly been reported for animals but, so far, not
      fungi. The authors therefore investigated tau aftereffects in the classic
      circadian model system Neurospora crassa. The standard laboratory strain frq+,
      the short-period mutant frq(1), and the long-period mutant frq(7) were entrained
      to 11 different photoperiods in a 24-h day (2-22 h) and to zeitgebers with six
      different T (16-26 h), and then released to constant darkness. tau-Aftereffects
      in response to different photoperiods correlated weakly with prior photoperiod in
      frq+ and were unsystematic in both period mutant strains. Strength and direction
      of the tau-aftereffect in zeitgeber cycles with different T depended on their
      length and on the strain, showing a negative correlation with zeitgeber length in
      frq+ and positive correlations in frq(1) and frq(7). It has been proposed that
      tau-aftereffects are based on interactions of oscillators within a cellular
      network. The present findings in Neurospora, which grows as a syncytium, suggest
      that tau-aftereffects also exist in circadian systems based on multioscillatory
      networks organized at the molecular level.

PMID- 20795880
TI  - Phase and period responses of the jerboa Jaculus orientalis to short light
      pulses.
AB  - The phase and period responses to short light pulses were studied in the jerboa,
      a seasonal, hibernating, nocturnal rodent from the Atlas region in Morocco. The
      jerboa, which is a saltatory species, showed precise activity onsets and offsets
      under a light-dark (LD) cycle using infrared captors to record locomotor
      activity. When released into constant darkness (DD), the majority of animals
      showed a circadian period (tau) < 24 h (mean tau = 23.89 +/- 0.13 h) and a
      lengthening of the activity span, alpha. Animals were subsequently exposed to up
      to eight 15-min light pulses, each separated by at least 2 wks, for up to 160
      days in DD. During this span, most individuals maintained robust circadian
      rhythmicity, with clearly defined activity onsets and offsets, similar levels of
      total activity, duration of alpha, and percent activity occurring during the
      subjective night. The phase response curve (PRC) is typical of other nocturnal
      rodents, with light eliciting delays during late subjective day and early
      subjective night (CT8-CT19) and advances during late subjective night to early
      subjective day (CT19-CT2). A dead zone, when light had no effect on phase, is
      observed during mid-subjective day (CT3-CT8). A few individuals showed large (> 9
      h) Type 0 phase resetting near the singularity region (CT19) that resulted in a
      complete phase reversal, but otherwise displayed normal phase-shifting responses
      at other CT times. The tau response curve showed a decrease in period from early
      to late subjective night with increases at other times, but these changes were
      small (maximum < 9 min) and highly variable. There was a distinct tendency for
      animals that had an initial short tau in DD to conserve a short tau during the
      series of light pulses and, inversely, for animals with long tau to conserve a
      long tau. This suggests possible constraints on the plasticity of variation of
      tau in relation to the endogenous period of the animal.

PMID- 20795881
TI  - Pacemaker phase control versus masking by light: setting the circadian chronotype
      in dual Octodon degus.
AB  - There are two main processes involved in the expression of circadian rhythmicity:
      entrainment and masking. Whereas the first operates via the central pacemaker to
      anticipate predictable environmental conditions, masking (mainly induced by
      light) functions as a direct modulator of the circadian output signal induced by
      nonpredictable events. The Chilean rodent Octodon degus presents both diurnal and
      nocturnal chronotypes when given free access to an exercise wheel. Two steady
      entrainment phases and graded masking by light seem to generate the wide
      variability of chronotypes in this species. The aim of this study was to
      characterize the differential masking by light according to the individual
      chronotypes, their stability over time, and the influence of wheel running
      availability and ambient temperature upon the degus' nocturnality. To this end,
      diurnal and nocturnal degus were subjected to ultradian cycles (1:1-h light-dark
      [LD]), with and without wheel running availability, and under both normal and
      high diurnal ambient temperature cycles. The present results show that diurnal
      and nocturnal degus present a stable masking by light, each according to its
      respective chronotype. Thus, whereas diurnal animals increased their activity
      with light, in nocturnal degus light induced a sharp drop in wheel running
      activity. These two types of masking responses appeared not only when the animals
      were synchronized to the 12:12-h LD cycle, but also under ultradian cycles.
      Different masking effects persisted when wheel running was made unavailable and
      when the animals shifted their circadian activity patterns in response to
      ultradian cycles or to diurnal exposure to high temperatures. In conclusion, our
      results show that the positive and negative masking effects of light on diurnal
      and nocturnal degus, respectively, seem to occur independently of relative phase
      control by the central pacemaker or the negative masking induced by high
      environmental temperatures.

PMID- 20795882
TI  - Feeding entrainment of food-anticipatory activity and per1 expression in the
      brain and liver of zebrafish under different lighting and feeding conditions.
AB  - Food provided on a periodic basis can act as a potent synchronizer, being a
      stronger zeitgeber than light for peripheral oscillators in mammals. In fish,
      however, little is known about the influence of feeding time on the circadian
      pacemaker and the relationship between central and peripheral oscillators. The
      aim of this research was to investigate the influence of mealtime on the activity
      rhythms, and on central (brain) and peripheral (liver) oscillators in zebrafish.
      The authors tested different feeding times under a light-dark (LD) cycle and the
      endogenous origin of food-anticipatory activity (FAA) by feeding zebrafish at a
      fixed time under constant bright-light conditions (LL). The authors then measured
      locomotor activity and the expression of the clock gene per1 in animals under a
      LD cycle and fed at random times during the light phase, with restricted feeding
      at the mid-light phase (ML) or with restricted feeding during the mid-dark phase
      (MD). Finally, the authors measured locomotor activity and per1 expression in
      fish maintained under LL under either random feeding or scheduled feeding.
      Zebrafish displayed FAA in all the groups fed at a fixed time but not when
      feeding was randomly scheduled. Under LL, fish entrainment persisted, and when
      released under fasting conditions FAA free-ran with a circa-24-h period. The
      expression of per1 in the brain of fish under LD showed a daily rhythm with the
      acrophase (peak time) at the end of the dark phase regardless of feeding
      schedule. This brain rhythm disappeared in LL fish under both random feeding and
      scheduled feeding. Feeding at MD advanced the phase of per1 in the liver by 7 h
      compared with the ML-fed group phase (23:54 versus 07:23 h, respectively). In
      addition, under LL scheduled feeding entrained the rhythms of per1 expression in
      the liver. This study reveals for the first time that scheduled feeding entrains
      peripheral oscillators in a fish species, zebrafish, which is a powerful model
      widely used for molecular genetics and for the study of basic clock mechanisms of
      the vertebrate circadian system.

PMID- 20795883
TI  - Effects of light and melatonin treatment on body temperature and melatonin
      secretion daily rhythms in a diurnal rodent, the fat sand rat.
AB  - Many mammals display predictable daily rhythmicity in both neuroendocrine
      function and behavior. The basic rest-activity cycles are usually consistent for
      a given species and vary from night-active (nocturnal), those mostly active at
      dawn and dusk (i.e., crepuscular), and to day-active (diurnal) species. A number
      of daily rhythms are oppositely phased with respect to the light/dark (LD) cycle
      in diurnal compared with nocturnal mammals, whereas others are equally phased
      with respect to the LD cycle, regardless of diurnality/nocturnality. Pineal
      produced melatonin (MLT) perfectly matches this phase-locked feature in that its
      production and secretion always occurs during the night in both diurnal and
      nocturnal mammals. As most rodents studied to date in the field of chronobiology
      are nocturnal, the aim in this study was to evaluate the effect of light
      manipulations and different photoperiods on a diurnal rodent, the fat sand rat,
      Psammomys obesus. The authors studied its daily rhythms of body temperature
      (T(b)) and 6-sulphatoxymelatonin (6-SMT) under various photoperiodic regimes and
      light manipulations (acute and chronic exposures) while maintaining a constant
      ambient temperature of 30 degrees C +/- 1 degrees C. The following protocols were
      used: (A) Control (CON) conditions 12L:12D; (A1) exposure to one light
      interference (LI) of CON-acclimated individuals for 30 min, 5 h after lights-off;
      (A2) short photoperiod (SP) acclimation (8L:16D) for 3 wks; (A3) 3 wks of SP
      acclimation with chronic LI of 15 min, three times a night at 4-h intervals; (A4)
      chronic exposure to constant dim blue light (470 nm, 30 lux) for 24 h for 3 wks
      (LL). (B) The response to exogenous MLT administration, provided in drinking
      water, was measured under the following protocols: (B1) After chronic exposure to
      SP with LI, MLT was provided once, starting 1 h before the end of photophase;
      (B2) after a continuous exposure to dim blue light, MLT was provided at 15:00 h
      for 2 h for 2 wks; (B3) to CON animals, MLT was given intraperitoneally (i.p.) at
      14:00 h. The results demonstrate that under CON acclimation, Psammomys obesus has
      robust T(b) and 6-SMT daily rhythms in which the acrophase (peak time) of T(b) is
      during the photophase, whereas that of 6-SMT is during scotophase. LI resulted in
      an elevation of T(b) and a reduction of 6-SMT levels. A significant difference in
      the response was noted between acute and chronic exposure to LI, particularly in
      6-SMT levels, which were lower than CON after LI and higher after chronic LI,
      implying an acclimation process. Constant exposure to blue light abolished T(b)
      and 6-SMT rhythms in all the animals. MLT administration resumed the T(b) daily
      rhythm in these animals, and had a recovery effect on the chronic LI-exposed
      animals, resulting in a T(b) decrease. Altogether, the authors show in this study
      the different modifications of T(b) rhythms and MLT levels in response to
      environmental light manipulations. These series of experiments may serve as a
      basis for establishing P. obesus as an animal model for further studies in
      chronobiology.

PMID- 20795884
TI  - Influence of seasonality on circadian motor activity rhythm in common marmosets
      during puberty.
AB  - The effect of puberty on circadian rhythmicity in nonhuman primates has been
      little studied, even though it has been demonstrated that puberty-related changes
      in circadian activity rhythm occur in a number of species, including humans. To
      characterize the motor activity rhythm during puberty in common marmosets
      (Callithrix jacchus), six animals was continuously monitored by actimeters
      between their 5th and 12th months of age. The animals were housed with their
      families in outdoor cages under seminatural conditions. Onset of puberty was
      determined from fecal estrogen and progesterone levels in females and androgen
      levels in males. The spectral power of the circadian component stabilized later
      in the last two animals to enter puberty. The bimodal characteristic of the
      active phase in this species became progressively more apparent over the course
      of the months in which the mean temperature was highest, irrespective of the
      animal's age. Although the onset of activity advanced after entry into puberty,
      this parameter showed a strong correlation with sunrise, indicating that
      seasonality influences this variable. Neither age nor climatic factors included
      in the regression model influenced the differences in phase angles between
      sunrise and onset of activity, and between sunset and offset of activity. Total
      activity was the only parameter influenced by age in the regression model,
      showing an increase after entry into puberty. Despite the evidence of pubertal
      influence on both the circadian component and total activity, under seminatural
      conditions seasonal factors may have a more important effect on motor activity
      rhythm in common marmosets.

PMID- 20795886
TI  - Working the night shift causes increased vascular stress and delayed recovery in
      young women.
AB  - Shiftwork has been associated with elevated blood pressure (BP) and decreased
      heart-rate variability (HRV), factors that may increase the long-term risk of
      cardiovascular-related mortality and morbidity. This study explored the effect of
      shiftwork on dynamic changes in autonomic control of HRV (cardiac stress),
      systolic BP and diastolic BP, i.e., SBP and DBP (vascular stress), and recovery
      in the same subjects working different shifts. By studying the same subjects, the
      authors could reduce the effect of possible contribution of between-subject
      variation from genetic predisposition and environmental factors. The authors
      recruited 16 young female nurses working rotating shifts--day (08:00-16:00 h),
      evening (16:00-00:00 h), and night (00:00-08:00 h)--and 6 others working the
      regular day shift. Each nurse received simultaneous and repeated 48-h ambulatory
      electrocardiography and BP monitoring during their work day and the following off
      duty day. Using a linear mixed-effect model to adjust for day shift, the results
      of the repeated-measurements and self-comparisons found significant shift
      differences in vascular stress. While working the night shift, the nurses showed
      significant increases in vascular stress, with increased SBP of 9.7 mm Hg. The
      changes of SBP and DBP seemed to peak during waking time at the same time on the
      day off as they did on the working day. Whereas HRV profiles usually returned to
      baseline level after each shift, the SBP and DBP of night-shift workers did not
      completely return to baseline levels the following off-duty day (p < .001). The
      authors concluded that although the nurses may recover from cardiac stress the
      first day off following a night shift, they do not completely recover from
      increases in vascular stress on that day.

PMID- 20795885
TI  - Increased sensitivity to light-induced melatonin suppression in premenstrual
      dysphoric disorder.
AB  - Increased sensitivity to light-induced melatonin suppression characterizes some,
      but not all, patients with bipolar illness or seasonal affective disorder. The
      aim of this study was to test the hypothesis that patients with premenstrual
      dysphoric disorder (PMDD), categorized as a depressive disorder in Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), have altered
      sensitivity to 200 lux light during mid-follicular (MF) and late-luteal (LL)
      menstrual cycle phases compared with normal control (NC) women. As an extension
      of a pilot study in which the authors administered 500 lux to 8 PMDD and 5 NC
      subjects, in the present study the authors administered 200 lux to 10 PMDD and 13
      NC subjects during MF and LL menstrual cycle phases. Subjects were admitted to
      the General Clinical Research Center (GCRC) in dim light (<50 lux) to dark
      (during sleep) conditions at 16:00 h where nurses inserted an intravenous
      catheter at 17:00 h and collected plasma samples for melatonin at 30-min
      intervals from 18:00 to 10:00 h, including between 00:00 and 01:00 h for baseline
      values, between 01:30 and 03:00 h during the 200 lux light exposure administered
      from 01:00 to 03:00 h, and at 03:30 and 04:00 h after the light exposure. Median
      % melatonin suppression was significantly greater in PMDD (30.8%) versus NC (
      0.2%) women (p = .040), and was significantly greater in PMDD in the MF (30.8%)
      than in the LL (-0.15%) phase (p = .047). Additionally, in the LL (but not the
      MF) phase, % suppression after 200 lux light was significantly positively
      correlated with serum estradiol level (p = .007) in PMDD patients, but not in NC
      subjects (p > .05).

PMID- 20795887
TI  - Modifications to weekend recovery sleep delay circadian phase in older
      adolescents.
AB  - Adolescents often report shorter time in bed and earlier wake-up times on school
      days compared to weekend days. Extending sleep on weekend nights may reflect a
      "recovery" process as youngsters try to compensate for an accumulated school-week
      sleep debt. The authors examined whether the circadian timing system of
      adolescents shifted after keeping a common late weekend "recovery" sleep
      schedule; it was hypothesized that a circadian phase delay shift would follow
      this later and longer weekend sleep. The second aim of this study was to test
      whether modifying sleep timing or light exposure on weekends while still
      providing recovery sleep can stabilize the circadian system. Two experiments
      addressed these aims. Experiment 1 was a 4-wk, within-subjects counterbalanced
      design comparing two weekend sleep schedule conditions, "TYPICAL" and "NAP."
      Compared to weeknights, participants retired 1.5 h later and woke 3 h later on
      TYPICAL weekends but 1 h later on NAP weekends, which also included a 2-h
      afternoon nap. Experiment 2 was a 2-wk, between-subjects design with two groups
      ("TYPICAL" or "LIGHT") that differed by weekend morning light exposure. TYPICAL
      and LIGHT groups followed the TYPICAL weekend schedule of Experiment 1, and the
      LIGHT group received 1 h of light (454-484 nm) upon weekend wake-up. Weekend time
      in bed was 1.5 h longer/night than weeknights in both experimental protocols.
      Participants slept at home during the study. Dim light melatonin onset (DLMO)
      phase was assessed in the laboratory before (Friday) and after (Sunday) each
      weekend. Participants were ages 15 to 17 yrs. Twelve participants (4 boys) were
      included in Experiment 1, and 33 (10 boys) were included in Experiment 2. DLMO
      phase delayed over TYPICAL weekends in Experiment 1 by (mean +/- SD) 45 +/- 31
      min and Experiment 2 by 46 +/- 34 min. DLMO phase also delayed over NAP weekends
      (41 +/- 34 min) and did not differ from the TYPICAL condition of Experiment 1.
      DLMO phase delayed over LIGHT weekends (38 +/- 28 min) and did not differ from
      the TYPICAL group of Experiment 2. In summary, adolescents phase delay after
      keeping a commonly observed weekend sleep schedule. Waking earlier or exposure to
      short-wavelength light on weekend mornings, however, did not stabilize circadian
      timing in this sample of youngsters. These data inform chronotherapy
      interventions and underscore the need to test circadian phase-shifting responses
      to light in this age group.

PMID- 20795888
TI  - Prior night sleep duration is associated with psychomotor vigilance in a healthy
      sample of police academy recruits.
AB  - Aviation, military, police, and health care personnel have been particularly
      interested in the operational impact of sleep restriction and work schedules
      given the potential severe consequences of making fatigue-related errors. Most
      studies examining the impact of sleep loss or circadian manipulations have been
      conducted in controlled laboratory settings using small sample sizes. This study
      examined whether the relationship between prior night sleep duration and
      performance on the psychomotor vigilance task could be reliably detected in a
      field study of healthy police academy recruits. Subjects (N = 189) were medically
      and psychiatrically healthy. Sleep-wake activity was assessed with wrist
      actigraphy for 7 days. Subjects performed the psychomotor vigilance task (PVT)
      for 5 min on a personal digital assistant (PDA) device before and after their
      police academy workday and on comparable times during their days off. Mixed
      effects logistic regression was used to estimate the probability of having > or
      =1 lapse on the PVT as a function of the previous night sleep duration during the
      7 days of field testing. Valid estimates of sleep duration were obtained for 1082
      nights of sleep. The probability of a lapse decreased by 3.5%/h sleep the night
      prior to testing. The overall probability of having a lapse decreased by 0.9%/h
      since awakening, holding hours of sleep constant. Perceived stress was not
      associated with sleep duration or probability of performance lapse. These
      findings demonstrate the feasibility of detecting sleep and circadian effects on
      cognitive performance in large field studies. These findings have implications
      regarding the daytime functioning of police officers.

PMID- 20795889
TI  - Quetiapine: novel uses in the treatment of depressive and anxiety disorders.
AB  - IMPORTANCE OF THE FIELD: Quetiapine, an atypical antipsychotic, has been approved
      for the treatment of schizophrenia, acute mania, bipolar depression and unipolar
      major depression. However, it is often used (off-label) to treat other depressive
      disorders and anxiety disorders in children and adults. AREAS COVERED IN THIS
      REVIEW: This article reviews the evidence for the safety and efficacy of
      quetiapine in these populations, as both monotherapy and augmentation to other
      psychotropics. WHAT THE READER WILL GAIN: This article provides an in-depth
      review of the published literature on the topic and also provides recommendations
      for use. TAKE HOME MESSAGE: There is strong evidence to support the use of
      quetiapine in major depressive and generalized anxiety disorders, and preliminary
      support for treatment-resistant and psychotic depression. There is reasonable
      evidence of its benefits as an augmenting agent in obsessive-compulsive disorder,
      while data in other anxiety disorders are limited but promising. While long-term
      tolerability data are limited, quetiapine appears well tolerated in the short
      term. Further randomized controlled trials are needed to confirm the efficacy and
      tolerability of quetiapine, both short- and long-term, in many of these
      conditions.

PMID- 20795890
TI  - Anticancer activity of sesquiterpene lactone from plant food (Carpesium
      rosulatum) in human cancer cell lines.
AB  - In the search for anticancer compounds against human cancer cells (A549, SK-OV-3,
      SK-MEL-2, XF498, HCT15), it was found that the chloroform extracts obtained from
      the whole plant food of Carpesium rosulatum MlQ exhibited significant anticancer
      activity. The structures and stereochemistry of these compounds were established
      on the basis of analysis of spectra including melting point, [alpha](D)(25),
      infrared, ultraviolet, electron ionization mass spectrometry, mass spectrometry,
      (1)H-nuclear magnetic resonance, (13)C-nuclear magnetic resonance and some
      chemical transformations as follows: compound 1, 4beta,10alpha-dihydroxy-guaia
      8alpha,12-olide; compound 2, 4beta,10alpha-dihydroxy-1(2),11(13)-guaiadien
      8alpha,12-olide; and compound 3, 3beta,8beta-dihydroxy-1alpha,5alpha-guaian
      10(14)-ene-6alpha,12-olide. Anticancer activity of compounds obtained from C.
      rosulatum on five tumor cells line was evaluated by sulforhodamine B methods.
      Compound 2 was significantly effective on the five human tumor cell lines.

PMID- 20795891
TI  - Emerging drugs for diabetic neuropathy.
AB  - IMPORTANCE OF THE FIELD: Diabetic neuropathy (DN) is a very common and disabling
      diabetes-related complication. DN is associated with significant morbidity and
      mortality. Diabetic peripheral neuropathy (DPN) can be painful in the earlier
      stages of the disease before becoming painless. Most of the currently available
      therapies are symptomatic (focusing on pain relief) rather than disease
      modifying. With the exception of good glycemic control, there is currently no
      effective treatment to slow the progression of or reverse DPN. AREAS COVERED IN
      THIS REVIEW: In this article, we review the epidemiology, pathogenesis, currently
      available and future treatments for DPN, and the potential development
      issues/challenges related to such new therapies. Literature search was performed
      using PubMed, Medline and Pharmaprojects from 1950 onwards. Search terms include
      a combination of terms such as diabetic neuropathy, pathogenesis,
      pathophysiology, mechanisms, treatment, therapy, oxidative/nitrosative stress,
      anti-oxidants, serotonin, nitrotyrosine, protein kinase C, aldose reductase,
      sodium channels, taurine, lipoic acid and poly (ADP-ribose) polymerase. WHAT THE
      READER WILL GAIN: The reader will gain an overview of the epidemiology, clinical
      features and risk factors of DN. In addition, the reader will have a better
      understanding of the mechanisms that underpin the development of DPN and their
      relationships to the current and future therapies. The reader will also develop
      an insight into the limitations of the current approach to DPN treatment and the
      potential avenues for future research. TAKE HOME MESSAGE: DN is a very common and
      disabling complication that currently has no effective treatments other than
      diabetes control. The pathogenesis of DPN is complex and multi-factorial. Several
      disease-modifying and symptomatic treatments are currently under development.
      Oxidative and nitrosative stress have been identified as key pathogenic factors
      in the development of DPN and new treatments target these pathways and/or their
      downstream consequences. Gene therapy and growth factors have also emerged as
      potential new therapies that target particular cellular compartments as opposed
      to being delivered systemically. The recognition of the difficulty in reversing
      established DN has focused efforts on slowing its progression.

PMID- 20795892
TI  - An investigation into the potential for different surface-coated quantum dots to
      cause oxidative stress and affect macrophage cell signalling in vitro.
AB  - The aim of this study was to investigate the ability of a series of different
      surface-coated quantum dots (QDs) to cause oxidative stress and affect cell
      signalling in J774.A1 macrophages. Organic QDs caused a significant (p < 0.001)
      decrease in glutathione (GSH) levels over 24 h, while COOH and NH(2) (PEG) QDs
      induced a significant decrease (p < 0.05) in GSH at 6 and 24 h only. J774.A1
      cytosolic Ca(2+) concentration significantly increased (p < 0.01) 30 min after
      treatment with all QDs. Trolox was, however, able to prevent the COOH and NH(2)
      (PEG) QD-induced Ca(2+) signal, but not the organic QD induced effect. All QDs
      tested were observed to have a relatively low ability to stimulate increased
      expression of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNF
      alpha). In conclusion, QDs differ in their interactions with macrophages
      according to their specific surface properties.

PMID- 20795893
TI  - Expression of inflammation-related cytokines following intratracheal instillation
      of nickel oxide nanoparticles.
AB  - The objective of this study was to examine what kinds of cytokines are related to
      lung disorder by well-dispersed nanoparticles. The mass median diameter of nickel
      oxide in distilled water was 26 nm. Rats intratracheally received 0.2 mg of
      nickel oxide suspended in distilled water, and were sacrificed from three days to
      six months. The concentrations of 21 cytokines including inflammation, fibrosis
      and allergy-related ones were measured in the lung. Infiltration of alveolar
      macrophages was observed persistently in the nickel oxide-exposed group.
      Expression of macrophage inflammatory protein-1alpha showed a continued increase
      in lung tissue and broncho-alveolar lavage fluid (BALF) while interleukin-1alpha
      (IL-1alpha), IL-1beta in lung tissue and monocyte chemotactic protein-1 in BALF
      showed transient increases. Taken together, it was suggested that nano
      agglomerates of nickel oxide nanoparticles have a persistent inflammatory effect,
      and the transient increase in cytokine expression and persistent increases in CC
      chemokine were involved in the persistent pulmonary inflammation.

PMID- 20795894
TI  - The effect of PEG-coated gold nanoparticles on the anti-proliferative potential
      of Specific Nutrient Synergy.
AB  - The role of PEG-coated gold nanoparticles (Au NPs) on the anti-proliferative
      effect of Specific Nutrient Synergy (SNS) on HTLV-1 infected (C91-PL and HuT-102)
      and non-infected (CEM and Jurkat) malignant T-lymphocytes cells, was
      investigated. When PEG-coated Au NPs (of different molecular weights) were added
      alone, there was no effect on either viability or proliferation of the leukemic
      cell lines studied. Treatment of cells with SNS and PEG (5 or 10 kDa) coated Au
      NP reduced significantly the proliferation in all cell lines tested; this reached
      more than 50% reduction as compared to the control for cells treated for 96 h.
      Data showed that the best anti-proliferative effect was obtained using SNS and Au
      NP coated with PEG of molecular weights of 5 and 10 kDa with almost no effect of
      PEG of lower molecular weights (0.75 and 2 kDa) or higher ones (20 kDa). This was
      true as well for HTLV-1 infected as for non-infected malignant T-lymphocytes.
      Electron microscopy results showed uptake of the gold particles to Jurkat cells.
      All described effects are specific to leukemia cell lines, and no effects were
      observed with freshly activated human mononuclear lymphocytes as control.

PMID- 20795895
TI  - Silver nanoparticles up-regulate Connexin43 expression and increase gap
      junctional intercellular communication in human lung adenocarcinoma cell line
      A549.
AB  - Silver nanoparticles (Ag NPs) are increasingly being used in wound dressings,
      medical settings, and various household products due to their unique properties
      and antimicrobial activity. Despite the widespread use of Ag NP products, the
      molecular mechanisms underlying the biological effects of Ag NPs remain unclear.
      Gap junctional intercellular communication (GJIC), formed by the connexin protein
      family, plays a critical role in the maintenance of tissue and organ homeostasis.
      This study was undertaken to investigate the effects of well characterized, PVP
      coated Ag NPs (69 +/- 3 nm) and silver nitrate on GJIC and connexin43 (Cx43)
      expression in human lung adenocarcinoma cell line A549. Our results showed that
      Ag NPs increased GJIC in A549 cells as assayed by dye transfer method. Western
      blot analysis showed that incubation of cells with Ag NPs significantly increased
      the expression of Cx43 protein. In addition, Ag NPs up-regulated expression of
      Cx43 mRNA in a dose-dependent manner. Silver nitrate failed to increase GJIC and
      the expression of Cx43 protein. It, however, increased Cx43 mRNA expression in
      A549 cells. Taken together, our results provide the first evidence that Ag NPs
      induced the increase of GJIC activity in A549 cells through up-regulation of Cx43
      protein, suggesting that Cx43 and GJIC may be one of the targets for Ag NPs
      biological effects.

PMID- 20795896
TI  - Physical-chemical characterization of tungsten carbide nanoparticles as a basis
      for toxicological investigations.
AB  - One task in risk assessment of engineered nanoparticles is toxicological studies.
      A suitable interpretation of these investigations demands a comprehensive
      physical-chemical characterization. Here, we present an approach to gain well
      dispersed nanoparticles in physiological media. Therefore, a step-by-step
      procedure is demonstrated on two different tungsten carbide nanopowders which can
      be transferred to other powders. The procedure includes a comprehensive powder
      characterization, followed by a preparation of a non-physiologic,
      electrostatically stable nanoparticle suspension and finally closes with
      investigations of the particles' behavior in different physiological media. Our
      study showed that the particles agglomerate in protein-free media. In this
      context, dependencies of mass- and surface-based nanoparticle concentrations as
      well as of different physiological media were analyzed. In the presence of bovine
      serum albumin (BSA) or serum, the agglomeration process is decelerated or, at the
      appropriate protein amount, prevented.

PMID- 20795897
TI  - A critical review of the biological mechanisms underlying the in vivo and in
      vitro toxicity of carbon nanotubes: The contribution of physico-chemical
      characteristics.
AB  - This critical review of the available human health safety data, relating to
      carbon nanotubes (CNTs), was conducted in order to assess the risks associated
      with CNT exposure. Determining the toxicity related to CNT exploitation is of
      great relevance and importance due to the increased potential for human exposure
      to CNTs within occupational, environmental and consumer settings. When this
      information is combined with knowledge on the likely exposure levels of humans to
      CNTs, it will enable risk assessments to be conducted to assess the risks posed
      to human health. CNTs are a diverse group of materials and vary with regards to
      their wall number (single and multi-walled CNTs are evident), length,
      composition, and surface chemistry. The attributes of CNTs that were identified
      as being most likely to drive the observed toxicity have been considered, and
      include CNT length, metal content, tendency to aggregate/agglomerate and surface
      chemistry. Of particular importance, is the contribution of the fibre paradigm to
      CNT toxicity, whereby the length of CNTs appears to be critical to their toxic
      potential. Mechanistic processes that are critical to CNT toxicity will also be
      discussed, with the findings insinuating that CNTs can exert an oxidative
      response that stimulates inflammatory, genotoxic and cytotoxic consequences.
      Consequently, it may transpire that a common mechanism is responsible for driving
      CNT toxicity, despite the fact that CNTs are a diverse population of materials.
      The similarity of the structure of CNTs to that of asbestos has prompted concern
      surrounding the exposure of humans, and so the applicability of the fibre
      paradigm to CNTs will be evaluated. It is also necessary to determine the
      systemic availability of CNTs following exposure, to determine where potential
      targets of toxicity are, and to thereby direct in vitro investigations within the
      most appropriate target cells. CNTs are therefore a group of materials whose
      useful exploitable properties prompts their increased production and utilization
      within diverse applications, so that ensuring their safety is of vital
      importance.

PMID- 20795898
TI  - Nano-intercalated rhodanese in cyanide antagonism.
AB  - Present studies have focused on nano-intercalated rhodanese in combination with
      sulfur donors to prevent cyanide lethality in a prophylactic mice model for
      future development of an effective cyanide antidotal system. Our approach is
      based on the idea of converting cyanide to the less toxic thiocyanate before it
      reaches the target organs by utilizing sulfurtransferases (e.g., rhodanese) and
      sulfur donors in a close proximity by injecting them directly into the blood
      stream. The inorganic thiosulfate (TS) and the garlic component diallydisulfide
      (DADS) were compared as sulfur donors with the nano-intercalated rhodanese in
      vitro and in vivo. The in vivo and in vitro experiments showed that DADS is not a
      more efficient sulfur donor than TS. However, the utilization of external
      rhodanese significantly enhanced the in vivo efficacy of both sulfur donor
      nitrite combinations, indicating the potential usefulness of enzyme nano-delivery
      systems in developing antidotal therapeutic agents.

PMID- 20795899
TI  - What's new in nanotoxicology? Implications for public health from a brief review
      of the 2008 literature.
AB  - Here, we review several articles of original research published in 2008 that
      concerned the toxicity of metal and carbon-based nanoparticles. Articles were
      selected from the MEDLINE PubMed database, all published or pre-published during
      2008 and relating to nanomaterials, -particles or -structures and toxicity or
      health. From the 746 articles, we concentrated on research into carbonaceous
      (carbon nanotubes [CNTs] and fullerenes) and metallic materials (pure metal,
      oxides), because these nanomaterials are produced and used worldwide and are the
      most relevant for public health. Unfortunately, due to the large variability in
      materials used and methods used conflicting data are generated hampering the risk
      assessment.

PMID- 20795900
TI  - Zinc oxide nanoparticles in modern sunscreens: an analysis of potential exposure
      and hazard.
AB  - Sunscreens containing metal oxide nanoparticles appear transparent on the skin
      and provide excellent protection against sunburn caused by UV radiation. While it
      is likely that nanoparticles remain on the surface of the skin of healthy adult
      humans, and thus are considered safe for use in sunscreens, there has been no
      comprehensive assessment of the impact on human health from exposure to the metal
      oxide nanoparticles destined for use in sunscreens, either in the workplace
      during the manufacturing process, in long-term use across a range of skin
      conditions, or upon release into the broader environment, either accidentally or
      consequent of normal sunscreen use. In this review, we focus on zinc oxide
      nanoparticles destined for use in modern sunscreens, and discuss the potential
      for human exposure and the health hazard at each stage of their manufacture and
      use. We highlight where there is a need for further research.

PMID- 20795901
TI  - A nanoparticle dispersion method for in vitro and in vivo nanotoxicity study.
AB  - The dispersion in air of nanoparticles of different sizes, materials and
      morphologies with controlled agglomeration involving aerosol delivery for in vivo
      and in vitro studies is one of the most difficult challenges in the field of
      nanoparticle toxicology. We describe here a nanoparticle dispersion system using
      an electrospray method to deliver airborne nanoparticles (approximately 10-100
      nm) with spatial uniformity and controllable particle concentration for in vitro
      and in vivo studies. With the dispersion method, single nanoparticles
      (polystyrene latex particles, TiO(2), Au, Mn, quantum dots, and carbon nanotubes)
      can be delivered to cells and animals via the air. The degree of agglomeration
      can be controlled by changing the suspension feeding rate to simulate realistic
      conditions for exposure studies.

PMID- 20795903
TI  - Endotoxin contamination of engineered nanomaterials.
AB  - Endotoxin has established health impacts and may be a potential confounding
      factor in toxicity studies of engineered nanomaterials (ENM). We aimed to
      characterize endotoxin contamination for a representative set of carbon-based
      ENM. The established method for quantifying endotoxin relies on its activity in a
      complex biochemical assay system. Because of their physical and chemical
      properties, measurement of endotoxin associated with many ENM presents non
      trivial technical challenges. We have made progress in identifying and
      implementing methods for ENM analysis with respect to endotoxin content,
      revealing varying levels of endotoxin contamination in the ENM examined here. The
      physical association of ENM and endotoxin and their shared physiological effects
      suggest the possibility that contaminating endotoxin may contribute to the
      toxicity that is ascribed to ENM. We found in this small number of samples that
      endotoxin levels were not related to type of ENM or surface area but may be
      introduced randomly during manufacture.

PMID- 20795902
TI  - The suitability of different cellular in vitro immunotoxicity and genotoxicity
      methods for the analysis of nanoparticle-induced events.
AB  - Suitable assays and test strategies are needed to analyze potential genotoxic and
      immunotoxic health effects caused by nanoparticle exposure. The development and
      validation of such methods is challenging because nanoparticles may show
      unexpected behavior, like aggregation or interference with optical measurements,
      when routine in vitro assays are performed. In our interdisciplinary study, the
      effects of inorganic gold (4.5 nm) and iron oxide (7.3 nm) nanoparticles with a
      narrow size distribution were tested on human cells using different assay
      systems. The results show that cytotoxicity as well as immunotoxicity and
      genotoxicity induced by these two inorganic nanoparticles was low or absent when
      using a panel of cell-based tests in different laboratories. However, several
      technical issues had to be tackled that were specific for working with
      nanoparticles. The methods used, their suitability for nanotoxicity testing, and
      the technical problems encountered are carefully described and discussed in this
      paper.

PMID- 20795904
TI  - Cytotoxicity of multi-walled carbon nanotubes in three skin cellular models:
      effects of sonication, dispersive agents and corneous layer of reconstructed
      epidermis.
AB  - The effects of multi-walled carbon nanotubes were investigated in SZ95 sebocytes,
      IHK keratinocytes and reconstructed human epidermises. Carbon nanotubes were
      subjected to dispersion protocols leading to different agglomeration states.
      Toxicological methods were chosen and adapted in order to ensure compatibility
      with nanotubes. Results show that: (i) Water-suspended nanotubes, as micrometric
      agglomerates, were not harmful to skin cells, except minor effects in
      keratinocytes, (ii) mild sonication slightly decreased nanotube agglomeration but
      increased cytotoxicity on keratinocytes, (iii) addition of hydroxypropylcellulose
      or Pluronic F108, which improved nanotube dispersion, masked the harmful effects
      of sonicated nanotubes. Altogether, these results indicate that carbon nanotubes
      induced cytotoxicity in human keratinocytes after a short exposure (24-48 h),
      particularly when they were sonicated before cell incubations. However, the
      cytotoxic effects of raw and sonicated nanotubes could be prevented in presence
      of dispersive agents. No cytotoxic effects were observed in SZ95 sebocytes or in
      stratified epidermises reconstructed in vitro.

PMID- 20795905
TI  - Pulmonary thrombosis in the mouse following intravenous administration of quantum
      dot-labeled mesenchymal cells.
AB  - Quantum dots (QDs) are emerging as novel diagnostic agents. Yet, only a few
      studies have examined the possible deleterious effects of QD-labeled stem cells.
      We assessed the potential toxic effects of QD-labeled human embryonic palatal
      mesenchymal (QD-HEPM) cells in male NOD/SCID mice for six months, following the
      administration of a single intravenous injection. Control animals were
      administered with non-labeled HEPM cells. No treatment-related clinical signs,
      hematological, or biochemical parameters were found in the QD-HEPM animals in
      comparison to control animals. Histologically, multifocal organizing thrombi were
      noted in the pulmonary arteries of all QD-HEPM animals from the one-week study
      group and in one animal from the one-month group. Additionally, increased
      severity of perivascular inflammation was noted at the injection sites of QD-HEPM
      animals from the one-week group. This is the first study reporting
      histopathological evidence for pro-thrombotic adverse effects mediated by QD
      labeling.

PMID- 20795906
TI  - Gold nanoparticles cellular toxicity and recovery: effect of size, concentration
      and exposure time.
AB  - Gold nanoparticles (AuNPs) are used in many applications; however, their
      interactions with cells and potential health risk(s) are not fully known. In this
      manuscript, we describe the interactions of AuNPs with human dermal fibroblasts
      and show that they can penetrate the plasma membrane and accumulate in large
      vacuoles. We also demonstrate that the uptake of the AuNPs is a function of time,
      their size and concentration. Specifically, we demonstrate that 45 nm AuNPs
      penetrate cells via clathrin-mediated endocytosis, while the smaller 13 nm enter
      mostly via phagocytosis. Furthermore, we provide evidence of cytoskeleton
      filament disruption as a result of AuNPs exposure and reconstitution during
      recovery (following AuNP removal), despite no changes in actin or beta-tubulin
      protein levels. In contrast, the expression of the extracellular matrix (ECM)
      proteins, collagen and fibronectin, was diminished in the cells exposed to AuNPs.
      We also examined the proliferation rates of cells exposed to AuNPs and show that
      its diminution is a function of apoptosis and speculate that apoptosis results
      from the number of vacuoles present in the cells, which is probably the main
      factor that disrupts the cytoskeleton causing cell area contraction and decreases
      in motility. Lastly, we also present data that indicates that AuNPs' damage to
      cells is not permanent and that the cells can completely recover as a function of
      AuNPs' size, concentration and exposure time. Taken together, our data suggest
      that AuNPs exert detrimental effects on cell function that could reverse
      following AuNPs removal.

PMID- 20795908
TI  - An ecotoxicological characterization of nanocrystalline cellulose (NCC).
AB  - The pulp and paper industry in Canada is developing technology for the production
      and use of nanocrystalline cellulose (NCC). A key component of the developmental
      work is an assessment of potential environmental risks. Towards this goal, NCC
      samples as well as carboxyl methyl cellulose (CMC), a surrogate of the parent
      cellulosic material, were subjected to an ecotoxicological evaluation. This
      involved toxicity tests with rainbow trout hepatocytes and nine aquatic species.
      The hepatocytes were most sensitive (EC20s between 10 and 200 mg/l) to NCC,
      although neither NCC nor CMC caused genotoxicity. In tests with the nine species,
      NCC affected the reproduction of the fathead minnow at (IC25) 0.29 g/l, but no
      other effects on endpoints such as survival and growth occurred in the other
      species at concentrations below 1 g/l, which was comparable to CMC. Based on this
      ecotoxicological characterization, NCC was found to have low toxicity potential
      and environmental risk.

PMID- 20795909
TI  - Biocompatibility of bacterial magnetosomes: acute toxicity, immunotoxicity and
      cytotoxicity.
AB  - In this study, we examined the acute toxicity, immunotoxicity, and cytotoxicity
      of bacterial magnetosomes (BMs). LD(50) of BMs injected into the sublingual vein
      of SD rats was 62.7 mg/kg. Further studies with injection of 40 mg/kg BMs showed
      no significant difference between BM-treated and control rats in terms of routine
      blood exam results, liver and kidney function tests, organ coefficients of major
      organs, or Stimulation Index (SI) of lymph cells with ConA and/or LPS antigens.
      Histological examination of major organs from 40 mg/kg BM-treated rats showed no
      obvious pathological changes except for increased number of vacuoles in livers,
      and somewhat thicker interlobular septa in lungs. BMs showed little cytotoxic
      effect on H22, HL60, or EMT-6 cells. Growth of all three cells was neither
      inhibited nor stimulated by incubation with 9 microg/ml BMs, which also had no
      effect on DNA content, cell size, or cell membrane integrity.

PMID- 20795910
TI  - Nano-silver - feasibility and challenges for human health risk assessment based
      on open literature.
AB  - This study aims at investigating feasibility and challenges associated with
      conducting a human health risk assessment for nano-silver based on the open
      literature by following an approach similar to a classical regulatory risk
      assessment. Gaps in the available data set, both in relation to exposures and
      hazard, do not allow reaching any definite conclusions that could be used for
      regulatory decision making. Results show that repeated inhalation in the
      workplace and possibly consumer inhalation may cause risks. Also (uncontrolled)
      nano-silver drug intake and burn treatment of large parts of the body with wound
      dressings may cause risks. Main future work should focus on generating
      occupational and consumer exposure data, as well as toxicity data on absorption
      (are particles or only ions absorbed?), information on genetoxicity, and further
      information on the toxicity following inhalation exposure to sizes and
      agglomeration states as uncounted in the workplace.

PMID- 20795911
TI  - In vivo effect of industrial titanium dioxide nanoparticles experimentally
      exposed to hairless rat skin.
AB  - We morphologically investigated animal skin exposed to W/O emulsion containing 10
      wt % ultrafine TiO(2) particles that had been characterized. After 4 h, exposed
      skin was investigated by light microscopy, confocal laser scanning microscopy
      (CLSM) and electron microscopy with energy-dispersive X-ray spectrometry (EDX).
      Light microscopic evaluation was also performed on the exposed skin after 24, 72
      and 168 h. Light microscopy did not show any morphological and
      immunohistochemical changes in the skin. Electron microscopy revealed that the
      most TiO(2) particles were localized in the interfollicular stratum disjunctum
      and the keratinized layer of follicular infundibulum. No TiO(2) particles were
      detected in the viable skin, which was confirmed by EDX. Furthermore, we
      demonstrated a specific TiO(2) affinity to the follicular opening area by light
      microscopy and low-vacuum scanning electron microscopy with EDX. Our study
      suggests that TiO(2) particles neither penetrate into viable cell layers nor
      biologically cause any cellular changes.

PMID- 20795912
TI  - Influence of size, surface area and microporosity on the in vitro cytotoxic
      activity of amorphous silica nanoparticles in different cell types.
AB  - Identifying the physico-chemical characteristics of nanoparticles (NPs) that
      drive their toxic activity is the key to conducting hazard assessment and guiding
      the design of safer nanomaterials. Here we used a set of 17 stable suspensions of
      monodisperse amorphous silica nanoparticles (SNPs) with selected variations in
      size (diameter, 2-335 nm), surface area (BET, 16-422 m(2)/g) and microporosity
      (micropore volume, 0-71 microl/g) to assess with multiple regression analysis the
      physico-chemical determinants of the cytotoxic activity in four different cell
      types (J774 macrophages, EAHY926 endothelial cells, 3T3 fibroblasts and human
      erythrocytes). We found that the response to these SNPs is governed by different
      physico-chemical parameters which vary with cell type: In J774 macrophages, the
      cytotoxic activity (WST1 assay) increased with external surface area (alphas
      method) and decreased with micropore volume (r(2) of the model, 0.797); in
      EAHY926 and 3T3 cells, the cytotoxic activity of the SNPs (MTT and WST1 assay,
      respectively) increased with surface roughness and small diameter (r(2), 0.740
      and 0.872, respectively); in erythrocytes, the hemolytic activity increased with
      the diameter of the SNP (r(2), 0.860). We conclude that it is possible to predict
      with good accuracy the in vitro cytotoxic potential of SNPs on the basis of their
      physico-chemical characteristics. These determinants are, however, complex and
      vary with cell type, reflecting the pleiotropic interactions of nanoparticles
      with biological systems.

PMID- 20795914
TI  - Relating the physicochemical characteristics and dispersion of multiwalled carbon
      nanotubes in different suspension media to their oxidative reactivity in vitro
      and inflammation in vivo.
AB  - Reactive oxygen species (ROS) production is important in the toxicity of
      pathogenic particles such as fibres. We examined the oxidative potential of
      straight (50 microm and 10 microm) and tangled carbon nanotubes in a cell free
      assay, in vitro and in vivo using different dispersants. The cell free oxidative
      potential of tangled nanotubes was higher than for the straight fibres. In
      cultured macrophages tangled tubes exhibited significantly more ROS at 30 min,
      while straight tubes increased ROS at 4 h. ROS was significantly higher in
      bronchoalveolar lavage cells of animals instilled with tangled and 10 mum
      straight fibres, whereas the number of neutrophils increased only in animals
      treated with the long tubes. Addition of dispersants in the suspension media lead
      to enhanced ROS detection by entangled tubes in the cell-free system. Tangled
      fibres generated more ROS in a cell-free system and in cultured cells, while
      straight fibres generated a slower but more prolonged effect in animals.

PMID- 20795913
TI  - Impact of silver nanoparticles on human cells: effect of particle size.
AB  - This work investigated the cytotoxicities of three silver nanoparticles (SNPs)
      SNP-5, SNP-20 and SNP-50 with different sizes ( approximately 5 nm, approximately
      20 nm and approximately 50 nm) using four human cell models (A549, SGC-7901,
      HepG2 and MCF-7). Endpoints included cell morphology, cell viability, cellular
      membrane integrity, oxidative stress and cell cycle progression. Observable
      deleterious effects on the cell morphologies and membrane integrity were induced
      by SNP-5 and SNP-20. SNPs elevated the ROS levels in cells and arrested the cells
      at S phase. Apoptosis occurred for 4-9% of the exposed cells. All these cellular
      responses as well as EC50 values were found to be size-dependent for the tested
      SNPs. Ultrastructural observations confirmed the presence of SNPs inside cells.
      Elemental analysis of silver in cells by ICP-MS showed that smaller nanoparticles
      enter cells more easily than larger ones, which may be the cause of higher toxic
      effects. The findings may assist in the design of SNP applications and provide
      insights into their toxicity.

PMID- 20795915
TI  - Small mammal-associated zoonoses.

PMID- 20795916
TI  - Hantaviruses and their hosts in Europe: reservoirs here and there, but not
      everywhere?
AB  - Five hantaviruses are known to circulate among rodents in Europe, and at least
      two among insectivores. Four (Dobrava, Saaremaa, Seoul, and Puumala [PUUV]
      viruses) are clearly associated with hemorrhagic fever with renal syndrome
      (HFRS). PUUV, the most common etiological agent of HFRS in Europe, is carried by
      the bank vole (Myodes glareolus), one of the most widespread and abundant mammal
      species in Europe. This host-virus system is among hantaviruses also the most
      studied one in Europe. However, HFRS incidence varies throughout the continent.
      The spatial as well as temporal variation in the occurrence of HFRS is linked to
      geographic differences in the population dynamics of the reservoir rodents in
      different biomes of Europe. While rodent abundance may follow mast seeding events
      in many parts of temperate Europe, in northern (N) Europe multiannual cycles in
      population density exist as the result of the interaction between rodent
      populations and specialist predator populations in a delayed density-dependent
      manner. The spatial distribution of hantaviruses further depends on parameters
      such as forest patch size and connectivity of the most suitable rodent habitats,
      and the conditions for the survival of the virus outside the host, as well as
      historical distribution patterns (phylogeographies) of hosts and viruses. In
      multiannually fluctuating populations of rodents, with population increases of
      great amplitude, one should expect a simultaneous build-up of recently hantavirus
      infected (shedding) rodents. The increasing number of infectious, virus-shedding
      rodents leads to a rapid transmission of hantavirus across the rodent population,
      and to humans. Our review discusses these aspects for PUUV, the only European
      hantavirus for which there is a reasonable, yet still far from complete,
      ecological continental-wide understanding. We discuss how this information could
      translate to other European hantavirus-host systems, and where the most important
      questions lie for further research.

PMID- 20795917
TI  - Antibodies to Tacaribe serocomplex viruses (family Arenaviridae, genus
      Arenavirus) in cricetid rodents from New Mexico, Texas, and Mexico.
AB  - Blood samples from 4893 cricetid rodents were tested for antibody (immunoglobulin
      G) to Whitewater Arroyo virus and Amapari virus to extend our knowledge of the
      natural host range and geographical distribution of Tacaribe serocomplex viruses
      in North America. Antibodies to arenaviruses were found in northern pygmy mice
      (Baiomys taylori), woodrats (Neotoma spp.), northern grasshopper mice (Onychomys
      leucogaster), oryzomys (Oryzomys spp.), deermice (Megadontomys nelsoni and
      Peromyscus spp.), harvest mice (Reithrodontomys spp.), and cotton rats (Sigmodon
      spp.) captured in New Mexico, Texas, or Mexico. Comparison of endpoint antibody
      titers to Whitewater Arroyo virus and Amapari virus in individual blood samples
      indicated that the Tacaribe complex viruses enzootic in Texas and Mexico are
      antigenically diverse.

PMID- 20795918
TI  - Evaluation of change in fatigue, self-efficacy and health-related quality of
      life, after a group educational intervention programme for persons with
      neuromuscular diseases or multiple sclerosis: a pilot study.
AB  - PURPOSE: An intervention for persons with neuromuscular diseases (NMD) or
      multiple sclerosis (MS) who experienced severe fatigue was developed which aimed
      at educating participants in maintaining a balance between capacity and load in
      their daily activities. This pilot study evaluated the results of this
      intervention. METHODS: Persons with NMD or MS who experienced severe fatigue were
      included. Outcome measures were: fatigue (Fatigue Severity Scale), health-related
      quality of life (HRQoL; SF-36) and self-efficacy (ALCOS-16). Changes in scores
      between the start of the intervention (T0) and 3 months post-intervention (T1)
      were tested with the Wilcoxon tests in the complete group and in subgroups
      (gender, education, high/low self-efficacy). RESULTS: Forty-three persons
      participated. Significant improvements of HRQoL were found for the domains role
      physical, mental health and general health perceptions. Subgroup analyses showed
      more improvement in males (fatigue, role-physical, vitality, bodily pain, general
      health perceptions), participants with lower education (role-physical, vitality)
      and participants with low self-efficacy at T0 (self-efficacy, mental health,
      general health perceptions) than in females, participants with higher education
      and participants with higher initial self-efficacy. CONCLUSION: This pilot-study
      provides preliminary evidence for the effectiveness of a group educational
      intervention in improving HRQoL without increasing fatigue in persons with NMD
      and MS.

PMID- 20795919
TI  - Self-efficacy and self-management after stroke: a systematic review.
AB  - PURPOSE: The purpose of this review is to examine (1) the influence of self
      efficacy on rehabilitation outcomes post-stroke, and (2) the evidence to support
      self-management interventions based on self-efficacy principals for stroke
      survivors. METHOD: Medline, Embase, Psychlit, Web of Science, AMED and Cochrane
      Databases for systematic reviews databases were searched for relevant articles in
      English between 2000 and ending in July 2009. Articles included (1) primary
      research testing relationships between self-efficacy and rehabilitation outcomes
      including the measuring impairment and activity or participation in a stroke
      population, and (2) research testing efficacy and effectiveness of self
      management interventions designed specifically for a stoke population in which
      the principle theoretical framework is self-efficacy or a similar control
      cognition. Methodological quality appraisal and data extraction was carried out
      by two reviewers. RESULTS: Of the 104 articles that were identified by the
      search, 22 met the criteria to be included in the review. There is evidence that
      self-efficacy is an important variable associated with various outcomes post
      stroke. These outcomes include quality of life or perceived health status,
      depression, ADL and, to a certain extent, physical functioning. Further empirical
      evidence is needed to extend these findings, and to determine whether self
      efficacy has additional predictive value over and beyond the objective measures
      of impairment. There is also emerging evidence of benefits to be gained from
      programmes that target self-management based on self-efficacy principles;
      however, the optimal format of delivering these interventions for stroke
      survivors is not clear. CONCLUSIONS: There is a need for researchers, to work
      together with other stakeholders to develop and test interventions that can
      support self-management skills and confidence to make continued progress after
      stroke. This could help to reduce some of the negative consequences of stroke
      such as reduced quality of life and social isolation.

PMID- 20795920
TI  - The importance of health literacy in physiotherapy practice.

PMID- 20795921
TI  - Mechanically assisted walking with body weight support results in more
      independent walking than assisted overground walking in non-ambulatory patients
      early after stroke: a systematic review.
AB  - QUESTION: Does mechanically assisted walking with body weight support result in
      more independent walking and is it detrimental to walking speed or capacity in
      non-ambulatory patients early after stroke? DESIGN: Systematic review with meta
      analysis of randomised trials. PARTICIPANTS: Non-ambulatory adult patients
      undergoing inpatient rehabilitation up to 3 months after stroke. INTERVENTION:
      Mechanically assisted walking (eg, treadmill, electromechanical gait trainer,
      robotic device, servo-motor) with body weight support (eg, harness with or
      without handrail, but not handrail alone) versus assisted overground walking of
      longer than 15 min duration. OUTCOME MEASURES: The primary outcome was the
      proportion of participants achieving independent walking. Secondary outcomes were
      walking speed measured as m/s during the 10-m Walk Test and walking capacity
      measured as distance in m during the 6-min Walk Test. RESULTS: Six studies
      comprising 549 participants were identified and included in meta-analyses.
      Mechanically assisted walking with body weight support resulted in more people
      walking independently at 4 weeks (RD 0.23, 95% CI 0.15 to 0.30) and at 6 months
      (RD 0.23, 95% CI 0.07 to 0.39), faster walking at 6 months (MD 0.12 m/s, 95% CI
      0.02 to 0.21), and further walking at 6 months (MD 55 m, 95% CI 15 to 96) than
      assisted overground walking. CONCLUSION: Mechanically assisted walking with body
      weight support is more effective than overground walking at increasing
      independent walking in non-ambulatory patients early after stroke. Furthermore,
      it is not detrimental to walking speed or capacity and clinicians should
      therefore be confident about implementing this intervention.

PMID- 20795922
TI  - Minimal difference between aerobic and progressive resistance exercise on
      metabolic profile and fitness in older adults with diabetes mellitus: a
      randomised trial.
AB  - QUESTION: Is progressive resistance training as effective as aerobic training of
      similar duration in sedentary older adults with diabetes mellitus? DESIGN: A
      randomised trial with concealed allocation, assessor blinding and intention-to
      treat analysis. PARTICIPANTS: Sixty people with Type 2 diabetes mellitus with
      glycosylated haemoglobin (HbA1c) between 8% and 10% in the past month.
      INTERVENTION: One group undertook progressive resistance exercise and the other
      group undertook aerobic exercise. Both groups completed 18 sessions over 8 weeks.
      In each session, the progressive resistance exercise group did nine resistive
      exercises while the aerobic exercise group did 50 minutes of aerobic exercise.
      OUTCOME MEASURES: HbA1c, blood glucose, lipid profile (total, high- and low
      density cholesterol and triglycerides), weight, body mass index, body fat, waist
      circumference, waist:hip ratio, blood pressure, and peak oxygen consumption.
      RESULTS: Forty-nine (82%) participants completed the intervention. HbA1c reduced
      by a similar amount in both groups (MD 0.1%, 95% CI -0.3 to 0.5). However,
      significant between-group differences occurred in change in waist circumference
      in favour of progressive resistance exercise (MD -1.8 cm, 95% CI -0.5 to -3.1),
      and in change in peak oxygen consumption in favour of aerobic exercise (MD 5.2
      ml/kg, 95% CI 0.0 to 10.4). CONCLUSIONS: Progressive resistance exercise has
      similar effects to aerobic exercise and therefore offers a useful alternative for
      patients unable to participate in aerobic exercise. TRIAL REGISTRATION:
      NCT01000519.

PMID- 20795923
TI  - Inspiratory muscle training improves maximal inspiratory pressure and may assist
      weaning in older intubated patients: a randomised trial.
AB  - QUESTIONS: Does inspiratory muscle training improve maximal inspiratory pressure
      in intubated older people? Does it improve breathing pattern and time to wean
      from mechanical ventilation? DESIGN: Randomised trial with concealed allocation
      and intention-to-treat analysis. PARTICIPANTS: 41 elderly, intubated adults who
      had been mechanically ventilated for at least 48 hr in an intensive care unit.
      INTERVENTION: The experimental group received usual care plus inspiratory muscle
      training using a threshold device, with an initial load of 30% of their maximal
      inspiratory pressure, increased by 10% (absolute) daily. Training was
      administered for 5 min, twice a day, 7 days a week from the commencement of
      weaning until extubation. The control group received usual care only. OUTCOME
      MEASURES: The primary outcome was the change in maximal inspiratory pressure
      during the weaning period. Secondary outcomes were the weaning time (ie, from
      commencement of pressure support ventilation to successful extubation), and the
      index of Tobin (ie, respiratory rate divided by tidal volume during a 1-min
      spontaneous breathing trial). RESULTS: Maximal inspiratory pressure increased
      significantly more in the experimental group than in the control group (MD 7.6
      cmH(2)0, 95% CI 5.8 to 9.4). The index of Tobin decreased significantly more in
      the experimental group than in the control group (MD 8.3 br/min/L, 95% CI 2.9 to
      13.7). In those who did not die or receive a tracheostomy, time to weaning was
      significantly shorter in the experimental group than in the control group (MD 1.7
      days, 95% CI 0.4 to 3.0). CONCLUSIONS: In intubated older people, inspiratory
      muscle training improves maximal inspiratory pressure and the index of Tobin,
      with a reduced weaning time in some patients. TRIAL REGISTRATION: NCT00922493.

PMID- 20795924
TI  - An inspiratory load enhances the antihypertensive effects of home-based training
      with slow deep breathing: a randomised trial.
AB  - QUESTION: Can adding an inspiratory load enhance the antihypertensive effects of
      slow breathing training performed at home? DESIGN: Randomised trial with
      concealed allocation. PARTICIPANTS: Thirty patients with essential hypertension
      Stage I or II. INTERVENTION: Experimental groups performed slow deep breathing at
      home, either unloaded or breathing against a load of 20 cmH(2)O using a threshold
      loaded breathing device. Participants trained for 30 min, twice daily for 8
      weeks. A control group continued with normal activities. OUTCOME MEASURES:
      Resting blood pressure and heart rate were measured at home and in the laboratory
      before and after the training period. RESULTS: Compared to the control group,
      systolic and diastolic blood pressure decreased significantly with unloaded
      breathing by means of 13.5 mmHg (95% CI 11.3 to 15.7) and 7.0 mmHg (95% CI 5.5 to
      8.5), [corrected] respectively (laboratory measures). With loaded breathing, the
      reductions were greater at 18.8 mmHg (95% CI 16.1 to 21.5) and 8.6 mmHg (95% CI
      6.8 to 10.4), respectively. The improvement in systolic blood pressure was 5.3
      mmHg (95% CI 1.0 to 9.6) greater than with loaded compared to unloaded
      [corrected] breathing. Heart rate declined by 8 beats/min (95% CI 6.5 to 10.3)
      with unloaded breathing, and 9 beats/min (95% CI 5.6 to 12.2) with loaded
      breathing. Very similar measures of blood pressure and heart rate were obtained
      by the patients at home. CONCLUSION: Home-based training with a simple device is
      well tolerated by patients and produces clinically valuable reductions in blood
      pressure. Adding an inspiratory load of 20 cmH(2)O enhanced the decrease in
      systolic blood pressure. TRIAL REGISTRATION: NCT007919689.

PMID- 20795925
TI  - A student-led progressive resistance training program increases lower limb muscle
      strength in adolescents with Down syndrome: a randomised controlled trial.
AB  - QUESTION: Does progressive resistance training improve muscle strength and
      physical function in adolescents with Down syndrome? DESIGN: Randomised
      controlled trial with concealed allocation, assessor blinding, and intention-to
      treat analysis. PARTICIPANTS: 23 adolescents with Down syndrome (17 boys, 6
      girls; mean age 15.6 +/- 1.6 years) were randomly assigned to either an
      experimental group (n = 11) or a control group (n = 12). INTERVENTION: The
      intervention was a student-led progressive resistance training program,
      comprising 6 exercises using weight machines performed twice a week for 10 weeks.
      Participants completed 3 sets of 12 repetitions of each exercise or until they
      reached fatigue. The intervention took place in a community gymnasium. The
      control group continued with their usual activities. OUTCOME MEASURES: The
      outcomes measured at baseline and immediately after the intervention phase were
      muscle strength (1 repetition maximum), a timed stairs test, and the grocery
      shelving task. RESULTS: The experimental group attended 90% of their scheduled
      sessions. They demonstrated improvement in lower limb muscle strength compared to
      the control group (MD 36 kg, 95% CI 15 to 58). There were no significant
      differences between the groups for upper limb muscle strength or physical
      function measures. No major adverse events were recorded. CONCLUSION: Progressive
      resistance training is a feasible and safe exercise option that can improve lower
      limb muscle strength in adolescents with Down syndrome. TRIAL REGISTRATION:
      ACTRN12608000261314.

PMID- 20795926
TI  - Reduced active control and passive range at the shoulder increase risk of
      shoulder pain during inpatient rehabilitation post-stroke: an observational
      study.
AB  - QUESTION: What factors at admission are associated with shoulder pain during
      stroke rehabilitation? DESIGN: Retrospective audit of medical histories and
      logistic regression. PARTICIPANTS: 94 people with primary diagnosis of stroke
      attending inpatient rehabilitation. OUTCOME MEASURES: Predictors were a battery
      of impairments, stroke-related factors, and patient characteristics. The outcome
      of interest was shoulder pain. RESULTS: Shoulder pain was present in 23% of
      patients at admission, and in a total of 35% of patients during inpatient stay.
      Patients with pain differed significantly (p = 0.04) from those without pain for
      several factors including age, longer time until rehabilitation admission,
      impaired movement of the arm (Motor Assessment Scale items), reduced passive
      range of movement, subluxation, and altered tone and sensation. No differences
      were found for many factors including neglect, cognitive impairment, side of
      stroke, and body weight. Logistic regression exploring the association between
      four predictors (shoulder range, Motor Assessment Scale items, subluxation, and
      altered sensation) and shoulder pain (outcome of interest) found that shoulder
      pain was reliably associated with two factors: reduced passive shoulder range (OR
      14%, 95% CI 3 to 64), and Motor Assessment Scale Upper Arm item score (OR 64%,
      95% CI 43 to 96). The model accurately classified 85% of patients. CONCLUSION:
      Shoulder pain is common and occurs early after stroke. Reduced active control and
      passive range at the shoulder appear to be risk factors for shoulder pain during
      inpatient rehabilitation post-stroke.

PMID- 20795927
TI  - Twelve months of resistance training can improve the cognitive functioning of
      older women living in the community.

PMID- 20795929
TI  - Ankle exercises in combination with intermittent ice and compression following an
      ankle sprain improves function in the short term.

PMID- 20795928
TI  - Additional physiotherapy during acute care reduces falls in the first 12 months
      after hip fracture.

PMID- 20795930
TI  - Impact of Event Scale-revised.

PMID- 20795931
TI  - The Depression Anxiety Stress Scale (DASS).

PMID- 20795932
TI  - Rethink the effect of resistance training on six-minute walk distance?

PMID- 20795934
TI  - Vitamin D deficiency: universal risk factor for multifactorial diseases?
AB  - In the Western world, the majority of morbidity and mortality are caused by
      multifactorial diseases. Some risk factors are related to more than one type of
      disease. These so-called universal risk factors are highly relevant to the
      population, as reduction of universal risk factors may reduce the prevalence of
      several types of multifactorial disease simultaneously. Vitamin D deficiency is
      traditionally seen as an etiological factor in bone disorders such as rickets and
      osteomalacia. Recent studies also suggest a role for vitamin D deficiency in
      multifactorial disorders, including progressive renal function loss and
      cardiovascular disease; it is also a risk factor for frailty. The potentially
      pleiotropic effects of vitamin D analogues support the hypothesis that vitamin D
      deficiency is a universal risk factor. Here we review molecular actions of the
      vitamin D receptor (VDR), to identify mechanisms and pathways for vitamin D
      deficiency as a universal risk factor. To identify genes directly regulated by
      the VDR, we searched for genes containing vitamin D response elements (VDREs). A
      further refinement was made by selecting only VDRE-containing genes with
      documented modulation by VDR analogues in vivo. Our search yielded a limited
      number of factors possibly related to pleiotropic effects of vitamin D, including
      growth factors, hormones, inflammatory factors and factors related to calcium
      homeostasis. Results from observational, intervention and mechanistic studies
      indicate that vitamin D is a universal risk factor involved in diverse
      multifactorial conditions. Further exploration of the multifaceted actions of
      vitamin D may pave the way for disease-overriding intervention strategies.

PMID- 20795935
TI  - Vitamin D supplementation: a promising approach for the prevention and treatment
      of strokes.
AB  - Vitamin D deficiency is highly prevalent due to lifestyle and environmental
      factors which limit sunlight induced vitamin D production in the skin. This
      "pandemic" of vitamin D deficiency is of concern because low levels of 25
      hydroxyvitamin D (25[OH]D) have been associated with cardiovascular,
      musculoskeletal, infectious, autoimmune and malignant diseases. Epidemiological
      studies have largely but not consistently shown that vitamin D deficiency is a
      risk factor for strokes. This is supported by associations of low 25(OH)D levels
      with cerebrovascular risk factors, in particular with arterial hypertension.
      Vitamin D has also been shown to exert neuroprotective, neuromuscular and
      osteoprotective effects which may reduce cognitive and functional impairments in
      poststroke patients. Hence, the current literature favours the notion that
      vitamin D supplementation is a promising approach for the prevention and
      treatment of strokes but accurate data from interventional studies are missing.
      Randomized controlled trials are therefore urgently needed to evaluate whether
      vitamin D supplementation reduces the incidence of strokes and improves the
      outcome of poststroke patients. We do, however, believe that currently published
      data on the multiple health benefits of vitamin D and the easy safe and
      inexpensive way by which it can be supplemented already argue for the prevention
      and treatment of vitamin D deficiency in order to reduce stroke associated
      morbidity and mortality.

PMID- 20795936
TI  - Vitamin D insufficiency and diabetes risks.
AB  - Diabetes is an increasing epidemic; hyperglycemia results from lack of insulin or
      inadequate insulin secretion following increases in insulin resistance. Huge
      costs are placed upon sufferers and health providers, aggravated as serious and
      disabling complications develop. Thus, measures to reduce the diabetic burden are
      public health concerns. Vitamin D, identified ~100 years ago, promotes calcium
      absorption and utilization, preventing and curing rickets & osteomalacia. Calcium
      is necessary for insulin secretion, suggesting vitamin D may contribute to
      maintaining insulin secretion. Vitamin D, formed in skin in bright sunshine, is
      scarce in foodstuffs. Data linking hypovitaminosis D to hyperglycemia, type 2
      diabetes (T2DM) and metabolic disorders increasing cardiovascular risk [metabolic
      'syndrome'] has accumulated over ~40 years. Many mechanisms are known whereby
      hypovitaminosis D could be causal, e.g. by increasing insulin resistance,
      reducing insulin secretion and increasing autoimmune or inflammatory damage to
      pancreatic islets. Major questions still to be answered are whether increasing
      vitamin D status to the maximum seen in healthy people would reduce the risk of
      diabetes, the severity of the disease or of its complications, including
      cardiovascular disease. These questions urgently require answers. If on-going/
      planned RCTs confirm causality, maintenance of adequate vitamin D status at the
      population level by food-fortification or supplementation would be cost-effective
      measures likely to reduce the burden and costs of diabetes to individuals and
      health services. Additionally, vitamin D(2/3) supplementation is cheap but
      whether some non-hypercalcemia-inducing analogue may prove safer has not yet been
      addressed at the population level.

PMID- 20795937
TI  - Vitamin D in atherosclerosis, vascular disease, and endothelial function.
AB  - Vitamin D deficiency has been linked to an increased risk of hypertension,
      diabetes, congestive heart failure, peripheral arterial disease, myocardial
      infarction, stroke, and related mortality, even after adjustment for traditional
      cardiovascular risk factors. Accumulating evidence from experimental, clinical,
      and epidemiological studies suggests that vitamin D may also be associated with
      several indices of vascular function, including the development and progression
      of atherosclerotic cardiovascular disease. These findings may provide at least a
      partial explanation for several recent epidemiologic studies implicating low
      vitamin D status in the pathogenesis of cardiovascular disease. However, many
      questions still remain. Only a handful of studies are currently available, and
      the results of these studies have generally been mixed. Additionally, it is
      unknown whether findings differ across varied subpopulations, including minority
      subgroups in the United States, younger adults, and those residing in areas with
      varying amounts of regular sunlight. Furthermore, the exact mechanism by which
      vitamin D may influence the atherosclerotic disease process has not yet been
      completely elucidated. In addition, if vitamin D is important in the etiology of
      atherosclerosis, it is unclear at what stage(s) in the atherosclerotic disease
      process vitamin D may exert its effects. Large-scale, well-conducted, placebo
      controlled clinical trials testing the efficacy of vitamin D supplementation in
      delaying, slowing, or reverting the atherosclerotic disease process have not yet
      been conducted. Until the results of these studies are available, we believe it
      is premature to recommend vitamin D as a therapeutic option in atherosclerosis.

PMID- 20795938
TI  - Vitamin D in chronic kidney disease: new potential for intervention.
AB  - Prevention of progressive renal function loss and its complications remains the
      main challenge in clinical nephrology. Although current therapeutic strategies
      aiming at reduction of blood pressure and proteinuria often slow down
      deterioration of renal function, still many patients progress to end-stage renal
      disease. The development of novel pharmacological approaches for treatment of
      chronic kidney disease (CKD) is therefore instrumental. Here we review the
      renoprotective potential of vitamin D and its analogues. In CKD patients, vitamin
      D deficiency is common and progression of CKD is associated with low (active)
      vitamin D levels. Moreover, in animal models of CKD, treatment with vitamin D
      (analogues) alone or in combination with renin-angiotensin-aldosterone system
      (RAAS) blockade reduces proteinuria, glomerulosclerosis and tubulointerstitial
      fibrosis. Potential underlying mechanisms include suppression of the RAAS,
      modulation of immune cell function and direct protective effects on renal cells
      such as podocytes. Whether vitamin D analogues could further optimize existing
      therapies in human renal disease is currently under investigation.

PMID- 20795939
TI  - Vitamin D biology in heart failure: molecular mechanisms and systematic review.
AB  - Vitamin D has recently been suggested as an important mediator of blood pressure
      and cardiovascular disease, including heart failure. In patient with heart
      failure, low vitamin D levels are associated with adverse outcome and correlate
      with established clinical correlates and biomarkers. Many precursor states of
      heart failure, such as hypertension, atherosclerosis, and diabetes are more
      prevalent in subjects with low vitamin D levels. Recent experimental data have
      provided clues how vitamin D might exert cardioprotective effects. The steroid
      hormone vitamin D regulates gene expression of many genes that play a prominent
      role in the progression of heart failure, such as cytokines and hormones.
      Specifically, vitamin D is a negative regulator of the hormone renin, the pivotal
      hormone of the renin-angiotensin system. Mechanistic insights were gained by
      studying mice deficient for the vitamin D receptor, which develop hypertension
      and adverse cardiac remodeling mediated via the renin-angiotensin system.
      Furthermore, vitamin D receptor is expressed in the heart and regulated under pro
      hypertrophic stimuli and vitamin D as receptor has been associated with the
      expression of other hypertrophic genes such as natriuretic peptides. So,
      epidemiological data and mechanistic studies have provided strong support for a
      potentially cardioprotective effect of vitamin D. It remains unclear if vitamin D
      supplementation is beneficial in preventing heart failure or if it could be a
      therapeutic addendum in the treatment of heart failure. This review summarizes
      current knowledge on vitamin D and its biology in heart failure.

PMID- 20795940
TI  - Accuracy of 25-hydroxyvitamin D assays: confronting the issues.
AB  - Measurement of 25-hydroxyvitamin D (25-OHD) is widely used for assessing vitamin
      D status. There has been a dramatic increase in 25-OHD requests over recent years
      prompting many laboratories to consider the use of automated immunoassays. To
      achieve higher throughput, these methods have abandoned the traditional solvent
      extraction of samples and are therefore more prone to non-specific interference.
      The Vitamin D External Quality Assessment Scheme (DEQAS) has revealed method
      related differences in 25-OHD results, raising concerns about the comparability
      and accuracy of different assays. This paper highlights some of the pre
      analytical, analytical and post-analytical issues which may influence the
      accuracy of 25-OHD assays and interpretation of results. Recent attention has
      focused on reconciling the relatively high results given by liquid chromatography
      tandem mass spectrometry (LC-MS/MS) to those of the DiaSorin radioimmunoassay
      (RIA) on which clinical decision points have previously been based. Data is
      presented on 20 DEQAS samples which were analysed by an LC-MS/MS assay developed
      as a candidate reference measurement procedure by the US National Institute of
      Standards and Technology (NIST). The NIST results were on average 11.2% lower
      than those given by routine LC-MS/MS methods. If confirmed, these results suggest
      that most routine LC-MS/MS assays are perhaps overestimating 25-OHD by failing to
      resolve a molecule having the same mass as 25-OHD(3) and a similar fragmentation
      pattern. All 25-OHD assays should be monitored by a proficiency testing scheme
      and the results made available to clinicians and editors of scientific journals.

PMID- 20795941
TI  - Vitamin D: evolutionary, physiological and health perspectives.
AB  - Vitamin D, the sunshine vitamin, has been important not only for the evolution of
      a healthy calcified vertebrate skeleton but it also evolved into a hormone that
      has a wide diversity of biologic effects. During exposure to sunlight the
      ultraviolet B radiation converts 7-dehydrocholesterol to previtamin D(3) which in
      turn rapidly isomerizes to vitamin D(3). Once formed, vitamin D(3) is metabolized
      in the liver to 25-hydroxyvitamin D(3) and in the kidneys to its active form 1,25
      dihydroxyvitamin D(3). 1,25-dihydroxyvitamin D(3) interacts with its vitamin D
      receptor in calcium regulating tissues to regulate calcium metabolism and bone
      health. It is now recognized that most cells in the body have a vitamin D
      receptor and they also have the capability of producing 1,25-dihydroxyvitamin
      D(3) which in turn is capable of regulating a wide variety of genes that have
      important functions in regulating cell growth, modulating immune function and
      cardiovascular health. Epidemiologic evidence and prospective studies have linked
      vitamin D deficiency with increased risk of many chronic diseases including
      autoimmune diseases, cardiovascular disease, deadly cancers, type II diabetes and
      infectious diseases. Vitamin D deficiency and insufficiency have been defined as
      a 25-hydroxyvitamin D <20 ng/ml and 21-29 ng/ml respectively. For every 100 IU of
      vitamin D ingested the blood level of 25-hydroxyvitamin D, the measure vitamin D
      status, increases by 1 ng/ml. It is estimated that children need at least 400
      1000 IU of vitamin D a day while teenagers and adults need at least 2000 IU of
      vitamin D a day to satisfy their body's vitamin D requirement. It is estimated
      that 1 billion people worldwide are vitamin D deficient or insufficient.
      Correcting and preventing this deficiency could have an enormous impact on
      reducing health costs worldwide.

PMID- 20795942
TI  - Vitamin D deficiency in cardiovascular and renal disease: new light shed on an
      old enemy.

PMID- 20795943
TI  - CEMOVIS on a pathogen: analysis of Bacillus anthracis spores.
AB  - BACKGROUND INFORMATION: Under conditions of starvation, bacteria of Bacillus ssp.
      are able to form a highly structured cell type, the dormant spore. When the
      environment presents more favourable conditions, the spore starts to germinate,
      which will lead to the release of the vegetative form in the life cycle, the
      bacillus. For Bacillus anthracis, the aetiological agent of anthrax, germination
      is normally linked to host uptake and represents an important step in the onset
      of anthrax disease. Morphological studies analysing the organization of the spore
      and the changes during germination at the electron microscopy level were only
      previously performed with techniques relying on fixation with aldehydes and
      osmium, and subsequent dehydration, which can produce artefacts. RESULTS AND
      CONCLUSIONS: In the present study, we describe the morphology of dormant spores
      using CEMOVIS (Cryo-Electron Microscopy of Vitreous Sections). Biosafety measures
      do not permit freezing of native spores of B. anthracis without chemical
      fixation. To study the influence of aldehyde fixation on the ultrastructure of
      the spore, we chose to analyse spores of the closely related non-pathogen
      Bacillus cereus T. For none of the investigated structures could we find a
      difference in morphology induced by aldehyde fixation compared with the native
      preparations for CEMOVIS. This result legitimizes work with aldehyde-fixed spores
      from B. anthracis. Using CEMOVIS, we describe two new structures present in the
      spore: a rectangular structure, which connects the BclA filaments with the basal
      layer of the exosporium, and a repetitive structure, which can be found in the
      terminal layer of the coat. We studied the morphological changes of the spore
      during germination. After outgrowth of the bacillus, coat and exosporium stay
      associated, and the layered organization of the coat, as well as the repetitive
      structure within it, remain unchanged.

PMID- 20795944
TI  - Overexpression of amyloid beta precursor protein enhances expression and
      secretion of ST6Gal1 in C2C12 myogenic cell line.
AB  - The Abeta (amyloid-beta) peptide is derived from the sequential cleavage of
      AbetaPP (amyloid-beta precursor protein) by two enzymes, the beta- and gamma
      secretases. The major beta-secretase, identified as the novel transmembrane
      aspartic protease BACE1 (beta site APP-cleaving enzyme 1), mediates the primary
      amyloidogenic cleavage of AbetaPP and initiates the production of Abeta. It has
      been implicated in the proteolytic processing of another substrate, namely
      ST6Gal1 (beta galactoside alpha2,6-sialyltransferase 1), which is the major
      alpha2,6-sialyltransferase responsible for the broad synthesis of glycoproteins
      and glycolipids. The present study investigated the effect of overexpression of
      AbetaPP on expression and secretion of ST6Gal1 in skeletal muscle cells by
      inducing overexpression of wild-type full-length 751-AbetaPP in the mouse
      myogenic cell line C2C12. Expression and secretion of the ST6Gal1 enzyme were
      analysed by Western blot and/or immunofluorescence staining. The results of our
      study demonstrated that AbetaPP overexpression in C2C12 cells increased the
      expression and the secretion of ST6Gal1 enzyme in vitro.

PMID- 20795945
TI  - AHR, a novel acute hypoxia-response sequence, drives reporter gene expression
      under hypoxia in vitro and in vivo.
AB  - ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is an
      early immediate gene. We have previously reported that ADAMTS1 was strongly
      induced by hypoxia. In this study, we investigated whether ADAMTS1 promoter
      driven reporter signal is detectable by acute hypoxia. We constructed the GFP
      (green fluorescent protein) expression vector [AHR (acute hypoxia-response
      sequence)-GFP] under the control of ADAMTS1 promoter and compared it with the
      constitutive GFP-expressing vector under the control of CMV (cytomegalovirus
      promoter-GFP). We transduced AHR-GFP and examined whether GFP signals can be
      detected under the acute hypoxia. When the human umbilical vein [HUVEC (human
      umbilical vein endothelial cells)] was transduced under normoxia, there were few
      GFP signals, while CMV-GFP showed considerable GFP signals. When HUVEC was
      stimulated with hypoxia, GFP signals from AHR-GFP gene were induced under hypoxic
      conditions. Notably, the GFP signals peaked at 3 h under hypoxia. In ischaemic
      hind limb model, transduced AHR-GFP showed hypoxic induction of GFP signals. In
      summary, we have demonstrated that the AHR system induced the reporter gene
      expression by acute hypoxia, and its induction is transient. This is the first
      report showing the unique acute hypoxia-activated gene expression system.

PMID- 20795947
TI  - Resistin contributes to neointimal formation via oxidative stress after vascular
      injury.
AB  - Resistin may play a major potential role in vascular remodelling and may
      contribute to atherogenesis. However, the role of VSMC (vascular smooth muscle
      cell)-derived resistin in neointimal formation is not well understood. We
      hypothesize that endogenous resistin derived from VSMCs may contribute to
      neointimal formation after vascular injury. VSMCs from thoracic aorta of adult
      Wistar rats were cultured. The carotid artery from adult Wistar rats was injured
      by balloon catheter. Resistin significantly increased migration and proliferation
      of VSMCs. Resistin siRNA (small interfering RNA) and resistin antibody
      significantly inhibited migration and proliferation of VSMCs induced by
      conditioned medium from stretched VSMCs. Resistin protein and mRNA expression
      significantly increased at 14 days after carotid injury. Resistin siRNA and NAC
      (N-acetylcysteine) significantly reduced resistin protein and mRNA expression
      induced by balloon injury. Carotid artery injury increased ROS (reactive oxygen
      species) production. Treatment with NAC and resistin siRNA decreased ROS
      production. The neointimal area was significantly increased after carotid injury
      and was significantly reduced by resistin siRNA and NAC. In conclusion, resistin
      increases migration and proliferation of VSMCs, and expression of resistin in
      carotid artery significantly increases after injury. Resistin siRNA attenuates
      neointimal formation after carotid injury partly through an antioxidative
      mechanism. Resistin may play a pivotal role in the pathogenesis of neointimal
      thickening after mechanical injury.

PMID- 20795946
TI  - Sitagliptin prevents the development of metabolic and hormonal disturbances,
      increased beta-cell apoptosis and liver steatosis induced by a fructose-rich diet
      in normal rats.
AB  - The aim of the present study was to test the effect of sitagliptin and exendin-4
      upon metabolic alterations, beta-cell mass decrease and hepatic steatosis induced
      by F (fructose) in rats. Normal adult male Wistar rats received a standard
      commercial diet without (C) or with 10% (w/v) F in the drinking water (F) for 3
      weeks; animals from each group were randomly divided into three subgroups:
      untreated (C and F) and simultaneously receiving either sitagliptin (CS and FS;
      115.2 mg/day per rat) or exendin-4 (CE and FE; 0.35 nmol/kg of body weight,
      intraperitoneally). Water and food intake, oral glucose tolerance, plasma
      glucose, triacylglycerol (triglyceride), insulin and fructosamine concentration,
      HOMA-IR [HOMA (homoeostasis model assessment) for insulin resistance], HOMA-beta
      (HOMA for beta-cell function) and liver triacylglycerol content were measured.
      Pancreas immunomorphometric analyses were also performed. IGT (impaired glucose
      tolerance), plasma triacylglycerol, fructosamine and insulin levels, HOMA-IR and
      HOMA-beta indexes, and liver triacylglycerol content were significantly higher in
      F rats. Islet beta-cell mass was significantly lower in these rats, due to an
      increase in the percentage of apoptosis. The administration of exendin-4 and
      sitagliptin to F animals prevented the development of all the metabolic
      disturbances and the changes in beta-cell mass and fatty liver. Thus these
      compounds, useful in treating Type 2 diabetes, would also prevent/delay the
      progression of early metabolic and tissue markers of this disease.

PMID- 20795948
TI  - 14-3-3 proteins are promising LRRK2 interactors.
AB  - Mutations in LRRK2 (leucine-rich repeat kinase 2) are the most common cause of
      familial PD (Parkinson's disease). Mutations that cause PD are found in either
      the GTPase or kinase domains of LRRK2 or an intervening sequence called the COR
      [C-terminus of ROC (Ras of complex proteins)] domain. As well as the two
      catalytic domains, LRRK2 possesses several protein-protein interaction domains,
      but their function and the proteins with which they interact are poorly
      understood. In this issue of the Biochemical Journal, Nichols et al. study the
      interaction of the N-terminal region of LRRK2 with 14-3-3 proteins, regulatory
      proteins that often bind to phosphorylated regions of components of cell
      signalling pathways. Using a combination of techniques, Nichols et al. have
      identified two residues (Ser910 and Ser935) that are critically responsible for
      14-3-3 binding. The interaction of LRRK2 with 14-3-3 proteins can prevent
      dephosphorylation of Ser910/Ser935 and stabilize LRRK2 structure, perhaps by
      influencing the dimerization of LRRK2. The ability to interact with 14-3-3
      correlates with the pattern of intracellular LRRK2 distribution. Collectively,
      these new results identify a potentially important regulatory mechanism of this
      complex protein and might provide ways to think about therapeutic opportunities
      for PD.

PMID- 20795949
TI  - Light on fluorescent lipids in rafts: a lesson from model membranes.
AB  - Tracking fluorescent lipids in cellular membranes has been applied for decades to
      shed light on membrane trafficking, sorting, endocytosis and exocytosis, viral
      entry, and to understand the functional relevance of membrane heterogeneity,
      phase separation and lipid rafts. However, fluorescent probes may display
      different organizing behaviour from their corresponding endogenous lipids. A full
      characterization of these probes is therefore required for proper interpretation
      of fluorescence microscopy data in complex membrane systems. Model membrane
      studies provide essential clues that guide us to design and interpret our
      experiments, help us to avoid pitfalls and resolve artefacts in complex cellular
      environments. In the present issue of the Biochemical Journal, Juhasz, Davis and
      Sharom demonstrate the importance of testing lipid probes systematically in
      heterogeneous model membranes of specific composition and well-defined
      thermodynamic properties. The phase-partitioning behaviour of fluorescent probes,
      alone and/or in combination, cannot simply be assumed, but has to be fully
      characterized.

PMID- 20795950
TI  - NMD: RNA biology meets human genetic medicine.
AB  - NMD (nonsense-mediated mRNA decay) belongs to the best-studied mRNA surveillance
      systems of the cell, limiting the synthesis of truncated and potentially harmful
      proteins on the one hand and playing an initially unexpected role in the
      regulation of global gene expression on the other hand. In the present review, we
      briefly discuss the factors involved in NMD, the different models proposed for
      the recognition of PTCs (premature termination codons), the diverse physiological
      roles of NMD, the involvement of this surveillance pathway in disease and the
      current strategies for medical treatment of PTC-related diseases.

PMID- 20795951
TI  - Functional diversity of the hnRNPs: past, present and perspectives.
AB  - The hnRNPs (heterogeneous nuclear ribonucleoproteins) are RNA-binding proteins
      with important roles in multiple aspects of nucleic acid metabolism, including
      the packaging of nascent transcripts, alternative splicing and translational
      regulation. Although they share some general characteristics, they vary greatly
      in terms of their domain composition and functional properties. Although the
      traditional grouping of the hnRNPs as a collection of proteins provided a
      practical framework, which has guided much of the research on them, this approach
      is becoming increasingly incompatible with current knowledge about their
      structural and functional divergence. Hence, we review the current literature to
      examine hnRNP diversity, and discuss how this impacts upon approaches to the
      classification of RNA-binding proteins in general.

PMID- 20795952
TI  - Chimaerism detection in bovine twins, triplets and quadruplets using sex
      chromosome-linked markers.
AB  - The phenomenon of chimaerism occurs in the majority of cattle twin pregnancies.
      The objectives of this study were to develop a powerful diagnostic test for
      chimaerism in bovine male and female co-twins using X and Y chromosome-linked
      markers and to determine the extent of chimaerism in twins, triplets and
      quadruplets. We developed a multiplex PCR set of three polymorphic markers on
      chromosome X (DIK2865, DIK2283, AGLA257), where the presence of >1 and >2 alleles
      per marker is sufficient to prove chimaerism in males and females, respectively.
      In addition, a specific segment on chromosome Y (BOV97M) is included in the set
      to indicate chimaerism in females. Visualization of chimaeric alleles was best
      for DNA extracted from blood, fair for DNA from vaginal smears and failed for DNA
      extracted from hair. The power of chimaerism identification using this set of
      markers for DNA extracted from blood was calculated as 99% in males and virtually
      100% in females. All females and males in heterosexual twins, triplets and
      quadruplets displayed evidence of a chimaeric allele in at least one and maximum
      of three of three X chromosome markers analysed. In addition, all females showed
      the presence of the BOV97M segment and were validated as chimaeric by the
      standard clinical diagnosis of impaired vaginal length. Quantitative PCR analysis
      of BOV97M copies in all twins vs. their sires showed a mean ratio of 45-68% in
      females and 39-49% in males, indicating a substantial symmetrical exchange of
      cells among all co-twins. The proposed analysis of X and Y chromosome-linked
      markers is advantageous to previous methods based on Y chromosome sequences only,
      because it detects chimaerism in both male and female co-twins. 

PMID- 20795953
TI  - Should there be a national core curriculum for anatomy?

PMID- 20795954
TI  - Acute surgery units: the future face of emergency surgery.

PMID- 20795955
TI  - Temporal artery biopsies: a fresh perspective.

PMID- 20795956
TI  - Asymmetric hearing loss in industry.

PMID- 20795957
TI  - Local recurrence of colorectal liver metastases following RFA--can we do BETA?

PMID- 20795959
TI  - 25, 50 & 75 years ago.

PMID- 20795958
TI  - Sir John Ramsay: the man and his writings.

PMID- 20795960
TI  - Revising the surgical registrar on-call roster.
AB  - BACKGROUND: The work hours of junior doctors have been in the spotlight since the
      mid-1980s. Rostering and the structure of surgical units aim to balance quality
      and continuity of patient care with reasonable working hours. METHODS: Actual
      hours worked during two 12-week surgical registrar rosters were compared.
      Compliance of each roster with fatigue recommendations was assessed with Fatigue
      Audit InterDyne (FAID, InterDynamics Pty Ltd, Adelaide, Australia) software.
      Workload was determined from an electronic prospective surgical audit. Impact of
      the roster change was discussed with consultants and registrars. The traditional
      roster started on 16 July 2007 and the fatigue-friendly roster on 14 July 2008.
      RESULTS: The total number of hours worked reduced by 11% (from 5085.17 h in 2007
      to 4530.85 h in 2008). Fatigue was eliminated (from 133.25 h in 2007 to 0 h in
      2008). Over the 12-month period, the operative workload for the Department of
      General Surgery increased by 18%. FAID compliance improved from 67.3 to 91.2%.
      Consultant and registrar satisfaction with the new roster was high. CONCLUSIONS:
      Safe working hours have been achieved for surgical registrars by restructuring
      the surgical units and implementing a new on-call rota without a perceived effect
      on patient care.

PMID- 20795961
TI  - Review: Dupuytren's disease in Asia and the migration theory of Dupuytren's
      disease.
AB  - BACKGROUND: The presentation of a Chinese patient with unilateral Dupuytren's
      disease (DD) prompted a literature search and a review of the epidemiology of DD
      in the Asian population as it has never been cumulatively reported. The purpose
      of this paper is to review all the reported cases of DD in the literature and
      aetiological links to DD elsewhere. METHODS: The literature was searched with a
      wide variety of terms, and subsequent references were analysed and further
      references investigated for other reported cases of DD in the Asian population.
      RESULTS: This review found 595 cases and has shown that DD is present to a
      variable extent in China (96 cases), Thailand (19 cases), Vietnam (one case),
      India (15 cases) and Japan (474 cases). A total of 54% had bilateral disease.
      Risk factors (diabetes, trauma, epilepsy, alcoholism, manual labour) were
      reportedly present in 65% of the patients, and a positive family history was
      reported in 9%. The average patient age was 67 years. CONCLUSION: This review
      shows that there is a low but significant incidence of DD across Asia, which
      supports the hypothesis of a widespread genetic susceptibility to the disease.
      Therefore, the prevalence of DD in this community is not likely due to sporadic
      genetic mutation as previously presumed but rather individual genetic
      susceptibility and that risk factors play a major role in the expression of DD in
      this population.

PMID- 20795962
TI  - Randomized controlled trial of laparoscopic anterior versus posterior
      fundoplication for gastro-oesophageal reflux disease.
AB  - BACKGROUND: The aim of the study was to compare the effect of laparoscopic
      anterior and posterior fundoplication on gastro-oesophageal reflux disease by
      means of a prospective randomized controlled trial. METHODS: One hundred and
      three patients were randomised to undergo either anterior (53) or posterior (50)
      fundoplication. Initial enrollment and subsequent clinical appointments were
      undertaken 1, 3, 6 and 12 months after the procedure using a standardized
      questionnaire. Ambulatory pH monitoring and manometry were undertaken both
      preoperatively and at approximately 3 months post-procedure. RESULTS: The mean
      operating time was similar in both groups (48 versus 52 min). Two operations in
      each group were converted to open surgery. Post-operative dysphagia in the first
      month was higher in the posterior fundoplication group compared with the anterior
      group (at 1 month, P= 0.002; and at 3 months, P= 0.014). The number of
      individuals suffering from post-operative heartburn was greater in the anterior
      fundoplication group (at 1 month, P= 0.008; at 3 months, P < 0.001; and at 6
      months, P= 0.002). Eight individuals required reoperation in the anterior group
      and two individuals in the posterior group (P= 0.057). CONCLUSION: Anterior and
      posterior fundoplication each have their advantages and disadvantages. There is
      an increased risk of early post-operative dysphagia after posterior
      fundoplication. Anterior fundoplication carries a greater risk of persistent or
      recurrent reflux. Overall, a posterior fundoplication produces a better
      management option for controlling gastro-oesophageal reflux disease when compared
      with an anterior fundoplication technique which utilizes unilateral fixation of
      the gastric fundus.

PMID- 20795963
TI  - Prosthesis related sepsis following laparoscopic adjustable gastric banding.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is well-recognized as
      a superior method to achieving durable weight loss in the medium term when
      compared with non-surgical methods of weight loss. In this paper, we described
      the clinical presentation and outcomes of patients presenting with band or band
      adjustment reservoir sepsis from our series from a single institution. METHODS:
      We conducted a retrospective review of prospectively collected clinical,
      anthropometric and biochemical data from patients who underwent LAGB placement
      over a five-year period at a metropolitan teaching hospital. Those patients
      requiring surgical intervention for prosthesis-related sepsis were included in
      the review. RESULTS: Of the 445 patients in this series, 10 (2.2%) developed
      prosthesis sepsis and required operative intervention. Three (0.7%) presented
      with reservoir sepsis requiring removal of the reservoir. One had band erosion
      identified and the entire prosthesis removed. In seven (1.5%) of the patients,
      infections occurred at the gastric band. Two patients presented with purulent
      peritonitis and underwent immediate band removal. The remainder presented with
      band abscesses and either had their band removed (three patients) or left in
      position and the sepsis treated with drainage and antibiotics (two patients).
      CONCLUSIONS: In our current series, a small proportion of LAGB patients developed
      prosthesis-related infection that typically required port or band removal and
      usually occurred early in the post-operative course. We have modified our
      prophylactic antibiotic regime and surgical technique as a result of this review.
      In selected cases of band infection, bands were salvaged with subsequent
      acceptable weight loss, suggesting that LAGB salvage in the presence of sepsis
      may be achievable in some patients.

PMID- 20795964
TI  - Prognosis and surgical treatment of gastric cancer invading adjacent organs.
AB  - BACKGROUND: The prognostic factors and surgical management of gastric cancer
      invading adjacent organs remains controversial. The aim was to provide valuable
      prognostic and surgical information on patients with gastric cancer invading
      adjacent organs. METHODS: The retrospectively study included 367 patients who
      underwent gastric resection for gastric cancer invading adjacent organs.
      Clinicopathologic variables were evaluated as predictors of long-term survival by
      univariate and multivariate analyses. Multivariate analysis was performed using
      Cox's proportional hazards model. RESULTS: The five-year survival rate was 10.1%,
      and median survival period was 14 months. The five-year survival rate was
      influenced by histologic type, lymph node metastasis, liver metastasis,
      peritoneal dissemination, extent of lymph node dissection and curability of
      operation. Of these, independent prognostic factors were lymph node metastasis
      (N2, N3 versus N0, N1, relative risk 2.028, P < 0.001), liver metastasis (present
      versus absent, relative risk 1.582, P= 0.023) and curative resection (no versus
      yes, relative risk 1.719, P < 0.001). A significant survival benefit for curative
      resection was observed with a five-year survival rate of 21.5% compared with non
      curatively resected cases (5.1%). CONCLUSIONS: In patients with gastric cancer
      invading adjacent organs, three independent prognostic factors were lymph node
      metastasis, liver metastasis, and curative resection. For patients with gastric
      cancer invading adjacent organs, we recommend performing combined organ resection
      in patients with locally advanced gastric carcinoma regardless of curability.

PMID- 20795965
TI  - Prevention and treatment of lymphorrhoea following surgery for gastric cancer.
AB  - BACKGROUND: Lymphorrhoea is a rare complication of abdominal surgery. However,
      there have been a few reports of lymphorrhoea following radical gastrectomy.
      Here, we retrospectively review the clinical analysis and treatment of
      lymphorrhoea based on our experiences. METHODS: We retrospectively reviewed a
      total of 1596 patients who underwent surgery for gastric cancer between January
      1995 and January 2007. D1 and D2 lymphadenectomies were performed in 1104
      patients, and D3 and D4 lymphadenectomies were performed in the other 492
      patients. Disrupted lymph vessels were ligated in 545 patients, and electrically
      cauterized in 559 patients. Before December 31 2000, total parenteral nutrition
      (TPN) was administered to all the patients, and after 1 January 2001, TPN was
      supplemented with octreotide in all the post-operative patients. RESULTS: The
      incidence of lymphorrhoea in patients with D3 and D4 lymphadenectomy was much
      higher than that in D1 and D2 lymphadenectomy patients (P < 0.05). In addition,
      the incidence of lymphorrhoea in patients in whom the electrotome cautery was
      significantly higher than that in patients who received ligation. The addition of
      octreotide to TPN can reduce the quantity and duration of lymphorrhoea (P <
      0.05). CONCLUSION: Ligating rather than cauterizing the disrupted lymph vessels
      can be done to minimize the incidence of lymphorrhoea. The combination of
      Octreotide and TPN appears to be an effective therapeutic modality for
      lymphorrhoea.

PMID- 20795966
TI  - Changing work patterns for benign upper gastrointestinal and biliary disease:
      1994-2007.
AB  - BACKGROUND: The evolution of surgical technology has impacted on surgical
      practice. We determined trends in surgical caseload for common benign biliary and
      upper gastrointestinal conditions in Australia over the last 15 years. METHODS:
      Using the Medicare Australia web site, the use of Medicare item numbers specific
      to gall stone, bariatric and anti-reflux procedures were determined nationally
      and for each Australian state for each year from 1994 to 2007. Rates of operative
      cholangiography, laparoscopic to open cholecystectomy conversion and bile duct
      exploration were calculated. Per capita use of bariatric procedures was also
      determined. Anti-reflux surgery was analysed as total and specific subgroups of
      anti-reflux procedures. RESULTS: The use of intra-operative cholangiography has
      increased over time, and the conversion to open cholecystectomy and application
      of common bile duct exploration both decreased. A rapid increase in restrictive
      bariatric procedures has occurred, and this has been followed by a similar
      increase in revision bariatric surgery and lap band adjustments. The application
      of anti-reflux surgery has also increased significantly with the repair of large
      hiatus hernia accounting for most of the increase over the last five years,
      whereas revision anti-reflux surgery remains uncommon. CONCLUSIONS: These data
      demonstrate significant increases in the application of some laparoscopic
      surgical techniques, particularly for morbid obesity. Future health-care planning
      will need to consider the impact of these changes.

PMID- 20795968
TI  - Microarray: an instrument for cancer surgeons of the future?
AB  - Microarray enables the study of thousands of genes simultaneously. While still in
      its infancy as a technique and with a number of barriers to be overcome,
      microarray is allowing scientists to thoroughly examine the molecular pathways of
      cancer pathogenesis. However, the adoption of microarray as a clinically
      applicable technique has been slow coming. Current literature suggests roles in
      the diagnosis of tumours of unknown origin, in the evaluation of prognostic
      markers, and in guiding treatment for recurrent and resistant malignancy. This
      review outlines the science of microarray and draws on clinical examples,
      including osteosarcoma, breast, prostate and pancreatic carcinomas, to highlight
      the potential of microarray as a technique of surgical importance.

PMID- 20795967
TI  - Surgical management of benign duodenal tumours.
AB  - BACKGROUND: While benign duodenal tumours are rare compared with malignant
      tumours, they comprise a wide variety of pathologies. Despite their diagnostic
      challenge, the optimal management of benign duodenal tumours remains undefined.
      We aimed to review the diagnosis and surgical treatment of benign duodenal
      tumours. METHODS: Records of all patients with post-operative pathological
      diagnosis of benign duodenal tumour were retrieved. Information on clinical
      presentations, diagnostic methods, tumour locations, surgical approaches,
      pathological results and patient outcomes were analysed. RESULTS: The operative
      spectrum included local resection in 8 cases, segmental duodenectomy in 1 case,
      subtotal gastrectomy in 1 case, papilla resection with sphincteroplasty in 3
      cases and pancreaticoduodenectomy in 5 cases. The post-operative pathology
      results indicated 5 cases of adenoma, 2 cases of tubular adenoma, 2 cases of
      villous adenoma, 2 cases of tubulovillous adenoma, 2 cases of hamartoma and 1
      case each of hamartomatous polyp, Brunner's adenoma, adenomyoma, fibromatosis and
      ectopic pancreas. Post-operatively, one patient died of unrelated disease, one
      case was lost in follow-up and the remaining patients survived recurrence-free
      with a good quality of life. CONCLUSION: The presentation of benign duodenal
      tumours is non-specific, with upper abdominal discomfort and upper
      gastrointestinal bleeding as common symptoms. Surgical resection is the
      preferable therapeutic choice with satisfactory prognosis.

PMID- 20795969
TI  - Cytokine response of electrolytic ablation in an ex vivo perfused liver model.
AB  - BACKGROUND: The inflammatory response following hepatic ablation depends on
      different factors including the method used, the duration and intensity of the
      treatment and the presence or absence of ischemia. Debate continues about the use
      of different modalities and whether some aspects of the response may be
      advantageous by releasing immunological active substances. Little data have been
      published concerning the cytokine response elicited by hepatic electrolytic
      ablation (EA). Study of an ex vivo liver model could allow for the evaluation of
      this response without the influence of confounding systemic factors. METHODS:
      Livers explanted from 11 pigs were perfused extracorporeally with normothermic
      autologous blood. Four of them underwent EA after 1 h of reperfusion. Serum
      samples were obtained up to 6 h after the reperfusion and assayed for IL-1 beta,
      IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IFN-gamma, TNF-alpha. RESULTS: Significant
      changes in the control group were observed for IL-6 after the second hour and IL
      8 after the first hour compared with baseline levels (P < 0.001). In the EA
      group, IL-6 and IL-12 were raised after the second hour and IL-8 and IL-10 after
      the first hour (P < 0.001). The comparison between groups showed significant
      differences for IL-2, IL-4 (decreased in the EA group compared with controls), IL
      10 and TNF-alpha (EA group increased compared with controls; P < 0.001).
      CONCLUSIONS: The ex vivo perfused liver model demonstrated changes in levels of
      IL-2, IL-4, IL-10 and TNF-alpha following hepatic EA.

PMID- 20795970
TI  - Functional and proteomic analysis of serum and cerebrospinal fluid derived from
      patients with traumatic brain injury: a pilot study.
AB  - BACKGROUND: An enhanced fracture healing response has been reported in patients
      with traumatic brain injury (TBI). This has been attributed to circulating
      humoral factors that are thought to be proteins produced and released by the
      injured brain. However, these factors remain unknown. The aim of this study was
      to identify osteogenic factors in serum and cerebrospinal fluid (CSF) from TBI
      patients. This was carried out using in vitro proliferation assays with the human
      foetal osteoblastic 1.19 cell line (hFOB) combined with a novel proteomic
      approach. METHODS: Serum was collected from brain-injured (n = 12) and non-brain
      injured (n = 9) patients with a comorbid femur shaft fracture. Similarly, CSF was
      obtained from TBI (n = 7) and non-TBI (n = 9) patients. The osteoinductive
      potential of these samples was determined by measuring the in vitro proliferation
      rate of hFOB cells. Highly osteogenic serum and CSF samples of TBI patients were
      chosen for protein analysis and were compared to those of non-brain-injured
      patients. A new hFOB cell-based method was used to enrich the proteins in these
      samples, which had a functional affinity for these osteoprogenitor cells. These
      enriched protein fractions were mapped using two-dimensional gel electrophoresis
      and protein imaging methods displaying serum and CSF proteins of brain-injured
      and control subjects that had an affinity for human osteoprogenitor cells.
      RESULTS: Serum and CSF derived from brain-injured patients demonstrated a greater
      osteoinductive potential (P < 0.05) than their non-brain-injured counterparts.
      Clear-cut differences in the pattern of proteins in two-dimensional gels were
      detected between TBI and control patients. Fourteen proteins were exclusively
      present in the serum of TBI patients, while other proteins were either up- or
      downregulated in samples collected from TBI patients (P < 0.05). CONCLUSION:
      Osteoinductive factors are present in the serum and CSF of brain-injured
      patients. These may include one or more of those proteins identified as having an
      affinity for osteoprogenitor cells that are either exclusively present or up- or
      downregulated in the serum and CSF of brain-injured patients.

PMID- 20795972
TI  - Aneurysm of the inferior vena cava: accurate preoperative diagnosis and surgical
      excision.

PMID- 20795971
TI  - S-phase fraction and DNA ploidy in oral leukoplakia.
AB  - BACKGROUND: The risk of malignant conversion in oral leukoplakia is well
      documented. Histological findings are often unreliable and it is difficult to
      predict on the basis of clinical and histopathological changes which leukoplakic
      lesion will turn malignant. METHODS: We used the technique of flow cytometry to
      evaluate the ploidy status, DNA index and S-phase fraction in leukoplakia, oral
      cancer and normal oral mucosal biopsies and compared it with histological
      findings. The study was carried out on 30 patients with oral cancer, 60 with
      leukoplakia and 30 with normal oral mucosal biopsies. RESULTS: The aneuploidy
      rate in oral cancers was 64%, for leukoplakia 20%, while all normal mucosal
      biopsies were diploid. Aneuploid lesions also had a greater S-phase fraction
      (SPF). The DNA Index (DI) of aneuploid oral cancers was 1.72 and aneuploid
      leukoplakias was 1.24. Leukoplakia specimens which showed histological evidence
      of dysplasia had aneuploidy rate of 38%, DI of 1.19 and SPF of 6.2%. The
      corresponding values for leukoplakia specimens without dysplasia were 14%, 1.09
      and 4.1%, respectively. CONCLUSION: The method of flow cytometry can be used to
      identify the subset of leukoplakia patients who are at a higher risk of malignant
      conversion. These patients could undergo more rigid surveillance or undergo
      excision biopsy of their lesions.

PMID- 20795973
TI  - Combined laparoscopic cholecystectomy and ligation of splenic artery aneurysm.

PMID- 20795974
TI  - Floor of mouth and tongue metastasis from malignant pleural mesothelioma.

PMID- 20795979
TI  - Re: Chappel v Hart res judicata?

PMID- 20795980
TI  - Re: Can the outcome of open carpal tunnel release be predicted? (ANZ J. Surg.
      2010; 80: 50-4).

PMID- 20795981
TI  - Re: Pancreatic neuroendocrine tumour (PNET) occurring with Guillian-Barre
      syndrome (ANZ J. Surg. 2010; 80: 297).

PMID- 20795982
TI  - Re: Rapunzel syndrome: an innovative surgical technique.

PMID- 20795983
TI  - Re: Is radical prostatectomy radical?

PMID- 20795984
TI  - Intestinal pseudo-obstruction due to mitochondrial cytopathy.

PMID- 20795985
TI  - Re: Acute traumatic appendicitis following blunt abdominal trauma.

PMID- 20795986
TI  - Re: An evaluation of the inaugural year of the Surgical Education and Training
      Programme in General Surgery: the South Australian experience.

PMID- 20795987
TI  - Re: Pyoderma gangrenosum: an uncommon cause of septic shock.

PMID- 20795988
TI  - Re: Keystone design flap: a tension-reducing modification.

PMID- 20795989
TI  - A case of a neuropathic diabetic foot ulcer causing rupture of the Achilles
      tendon.

PMID- 20795990
TI  - Re: Brown-Sequard syndrome produced by traumatic cervical disc herniation.

PMID- 20795993
TI  - The emerging fields of laparoendoscopic single-site surgery (less) and natural
      orifice transluminal endoscopic surgery (notes).

PMID- 20795994
TI  - Are LESS and NOTES ready for prime time in urology?

PMID- 20795995
TI  - Current prospects for the chemoprevention of prostate cancer.

PMID- 20795996
TI  - Cardiopulmonary bypass and renal cell carcinoma with level iv tumour thrombus:
      can deep hypothermic circulatory arrest limit perioperative mortality?

PMID- 20795997
TI  - S1 guideline for diagnostic evaluation in androgenetic alopecia in men, women and
      adolescents.
AB  - Androgenetic alopecia (AGA) is the most common hair loss disorder, affecting both
      men and women. Due to the frequency and the often significant impairment of life
      perceived by the affected patients, competent advice, diagnosis and treatment is
      particularly important. As evidence-based guidelines on hair disorders are rare,
      a European consensus group was constituted to develop guidelines for the
      diagnostic evaluation and treatment of AGA. This S1 guideline for diagnostic
      evaluation of AGA in men, women and adolescents reviews the definition of AGA and
      presents expert opinion-based recommendations for sex-dependent steps in the
      diagnostic procedure.

PMID- 20795998
TI  - Interobserver variability of teledermoscopy: an international study.
AB  - BACKGROUND: Teledermoscopy is a rapidly developing field of dermatology with
      studies demonstrating excellent agreement with face-to-face diagnosis. However,
      we are unaware of studies evaluating interobserver variability in diagnosis
      between dermatologists from different continents. This evaluation is important to
      determine the robustness of teledermoscopy and allow comparisons to be made
      between different studies. OBJECTIVES: To assess the interobserver diagnostic
      variability between five independent experienced dermatologists (A-E) in New
      Zealand, Australia and the U.S.A. METHODS: Images from 979 lesions from 206
      patients were distributed to five dermatologists. The lesions were viewed and
      diagnoses recorded using MoleMap Diagnose (MoleMap, Auckland, New Zealand)
      software. The diagnoses were analysed for interobserver variability. RESULTS:
      There was excellent agreement between four of five dermatologists (A-D) for
      lesions that were agreed upon as melanoma (kappa = 0.81-0.97) and benign naevus
      (kappa = 0.77-0.82).The fifth dermatologist (E) made a more frequent diagnosis of
      atypical naevus and melanoma than the others. For nonmelanocytic lesions, there
      was moderate to very good agreement for seborrhoeic keratosis (kappa = 0.64-0.80)
      and basal cell carcinoma (kappa = 0.55-0.67), but poor agreement for invasive
      squamous cell carcinoma (SCC) (kappa = 0.05-0.15). Agreement for actinic
      keratosis (kappa = 0.32-0.67) and SCC in situ (kappa = 0.15-0.32) was only
      moderate. When atypical and benign naevi were grouped together and actinic
      keratosis and SCC in situ grouped together, there was better agreement among all
      dermatologists. There was good ability to distinguish malignant from benign
      lesions (kappa = 0.57-0.93). CONCLUSIONS: There was good agreement among
      dermatologists A-D but dermatologist E varied from the group with more frequent
      diagnosis of melanoma and atypical naevus. This difference could be due to
      different definition of terms with lack of consensus guidelines in definition of
      atypical naevus, lack of familiarity with the specific patient population and/or
      diagnostic drift.

PMID- 20795999
TI  - Elicitation of the immune response to p-phenylenediamine in allergic patients:
      the role of dose and exposure time.
AB  - BACKGROUND: Usage of hair dye products containing p-phenylenediamine (PPD) is a
      concern for PPD-allergic individuals. OBJECTIVES: The present study investigates
      the role of dose and exposure time on elicitation of allergic contact dermatitis
      under conditions of permanent hair dyeing. METHODS: Elicitation responses after
      application of a typical hair dye product containing 2% PPD for 30 min followed
      by rinsing were analysed in 38 PPD-allergic individuals with a documented history
      of hair dye-related allergy. Skin binding experiments in vitro were performed to
      distinguish the dose available for elicitation from the dose applied. RESULTS: A
      positive reaction was elicited in 20 of 20 patients with grades ++ to +++ and 12
      of 18 with grade + according to the classification of the International Contact
      Dermatitis Research Group. Under conditions of diagnostic patch testing (48 h
      exposure), the dose available for elicitation is more than 10-fold higher
      compared with the dose available for hair dyeing (30-min exposure, rinsing of
      product). CONCLUSIONS: This investigation demonstrates that under simulated hair
      dye use conditions the actual exposure to PPD is more than an order of magnitude
      lower than under diagnostic patch testing, although sufficient to elicit a
      clearly noticeable reaction in 84% of PPD patch test-positive individuals.

PMID- 20796000
TI  - Computed tomography lymphography for the detection of sentinel nodes in patients
      with gastric carcinoma.
AB  - The sentinel node (SN) concept has been found to be feasible in gastric cancer.
      However, the lymphatic network of gastric cancer may be more complex, and it may
      be difficult to visualize all the SN distributed in unexpected areas by
      conventional modalities. In this study, we evaluate the feasibility and efficacy
      of CT lymphography for the detection of SN in gastric cancer. A total 24 patients
      with early gastric cancer were enrolled in the study. Three modalities (CT
      lymphography, dye and radioisotope [RI] methods) were used for the detection of
      SN. The images of CT lymphography were obtained at 10 min after injection of
      contrast agents. The SN were successfully identified by CT lymphography in 83.3%
      of patients; detection rates by the dye and RI methods were 95% and 100%,
      respectively. Most patients, in whom SN were successfully detected by CT
      lymphography, had positive results at 5 min after injection of the contrast
      material. The SN stations detected by CT lymphography were consistent with or
      included those detected by dye and/or RI methods. In conclusion, CT lymphography
      for the detection of SN in gastric cancer is feasible and has several advantages.
      However, based on this initial experience, CT lymphography had a relatively low
      detection rate compared with conventional methods, and further efforts will be
      necessary to improve the detection rate and widen the clinical application of CT
      lymphography for the detection of SN in gastric cancer.

PMID- 20796001
TI  - Reducing fracture risk with calcium and vitamin D.
AB  - Studies of vitamin D and calcium for fracture prevention have produced
      inconsistent results, as a result of different vitamin D status and calcium
      intake at baseline, different doses and poor to adequate compliance. This study
      tries to define the types of patients, both at risk of osteoporosis and with
      established disease, who may benefit from calcium and vitamin D supplementation.
      The importance of adequate compliance in these individuals is also discussed.
      Calcium and vitamin D therapy has been recommended for older persons, either
      frail and institutionalized or independent, with key risk factors including
      decreased bone mineral density (BMD), osteoporotic fractures, increased bone
      remodelling as a result of secondary hyperparathyroidism and increased propensity
      to falls. In addition, treatment of osteoporosis with a bisphosphonate was less
      effective in patients with vitamin D deficiency. Calcium and vitamin D
      supplementation is a key component of prevention and treatment of osteoporosis
      unless calcium intake and vitamin D status are optimal. For primary disease
      prevention, supplementation should be targeted to those with dietary
      insufficiencies. Several serum 25-hydroxyvitamin D (25(OH)D) cut-offs have been
      proposed to define vitamin D insufficiency (as opposed to adequate vitamin D
      status), ranging from 30 to 100 nmol/l. Based on the relationship between serum
      25(OH)D, BMD, bone turnover, lower extremity function and falls, we suggest that
      50 nmol/l is the appropriate serum 25(OH)D threshold to define vitamin D
      insufficiency. Supplementation should therefore generally aim to increase 25(OH)D
      levels within the 50-75 nmol/l range. This level can be achieved with a dose of
      800 IU/day vitamin D, the dose that was used in successful fracture prevention
      studies to date; a randomized clinical trial assessing whether higher vitamin D
      doses achieve a greater reduction of fracture incidence would be of considerable
      interest. As calcium balance is not only affected by vitamin D status but also by
      calcium intake, recommendations for adequate calcium intake should also be met.
      The findings of community-based clinical trials with vitamin D and calcium
      supplementation in which compliance was moderate or less have often been
      negative, whereas studies in institutionalized patients in whom medication
      administration was supervised ensuring adequate compliance demonstrated
      significant benefits.

PMID- 20796002
TI  - Outcome after restorative proctocolectomy in children and adolescents.
AB  - AIM: The results including function and quality of life (QOL) of restorative
      proctocolectomy (RPC) performed in children and adolescents with ulcerative
      colitis (UC), familial adenomatous polyposis (FAP) and idiopathic megarectum were
      determined. METHOD: Twenty-one patients of a median age of 15 (10-17) years
      underwent RPC between 1995 and 2006. The indication, use of covering ileostomy,
      morbidity and mortality were recorded. A structured questionnaire was completed
      by telephone interview to assess long-term function. The Cleveland Clinic Scoring
      (CCS) System was used for the assessment of faecal incontinence and the modified
      McMaster proforma for QoL. RESULTS: There was no mortality. At a median follow-up
      of 65.5 (26-168) months, all patients had an intact pouch. One had a long
      standing ileostomy. Median daytime and nocturnal stool frequencies were 4 (2-16)
      and 0 (0-3). The mean CCS was 1.47, with only one patient scoring more than 10.
      Eighteen of 20 patients were satisfied with the result; two patients had a worse
      QoL (McMaster score >8). One patient had a permanent stoma following pouch sepsis
      and one had symptoms of pouchitis. CONCLUSION: RPC can be performed in children
      and adolescents with good functional outcome and acceptable QoL.

PMID- 20796003
TI  - Incidentally diagnosed unusual ascending aorta mass.
AB  - A 44-year-old female, with no medical history, was admitted to the cardiology
      department because of mild exertional dyspnea. Transthoracic and transesophageal
      echocardiography showed highly mobile, mass-like lesion in the aortic root. The
      patient was operated in the same week and a 1 cm * 6 cm soft tissue was excised
      from the ascending aorta. Pathological examination revealed a fibrin clot
      surrounded by a fibrous cap.

PMID- 20796004
TI  - Emergency room thoracotomy: has availability triumphed over advisability in the
      care of trauma patients in Australasia?

PMID- 20796005
TI  - Smoking out tobacco: a vital preventive role for emergency departments.

PMID- 20796006
TI  - Credentialing a new skill: what should the standard be for emergency department
      ultrasound in Australasia?

PMID- 20796007
TI  - Review article: Safety profile of propofol for paediatric procedural sedation in
      the emergency department.
AB  - The use of propofol for paediatric procedural sedation (PPS) is increasing
      because of its favourable pharmacodynamic profile. Its paediatric use has been
      limited in some ED (emergency departments) because of the perceived high rate of
      serious adverse events in comparison with other sedation agents. A systematic
      literature review of propofol use for PPS outside the operating theatre
      environment from 1966 to 2008 was carried out to profile the adverse event rate
      in comparison with other procedural sedation agents. Sixty studies with a total
      of 17,066 paediatric propofol sedations in a variety of hospital settings were
      identified. The incidence of complications were: desaturation 9.3%, apnoea 1.9%,
      assisted ventilation 1.4%, hypotension 15.4%, unplanned intubation 0.02%, emesis
      post procedure 0.14%, laryngospasm 0.1% and bradycardia 0.1%. There were no
      reported incidents of aspiration or emesis during sedation and there were no
      deaths associated with procedural propofol sedation. The use of propofol for PPS
      is associated with a low rate of minor adverse events that are all reversible
      with minimal intervention and do not produce long-term sequelae and occur at
      similar rates to minor adverse events experienced with other sedation agents.
      Major adverse events with propofol sedation are extremely rare and appropriate
      patient and procedure selection would decrease these risks further. The
      increasing use of propofol for ED PPS is supported by the current evidence
      because of its comparable adverse event rate to other agents.

PMID- 20796008
TI  - Obesity significantly increases the difficulty of patient management in the
      emergency department.
AB  - OBJECTIVE: To determine which aspects of ED management are adversely affected by
      patient obesity, to determine the level of obesity above which management is made
      more difficult and to make recommendations on how these effects might be
      mitigated. METHODS: This was a cross-sectional survey of patients and the staff
      caring for them in a single ED. Doctors, nurses and radiographers managing
      consecutive patients, during a range of enrolment periods, completed a self
      administered questionnaire. Each was asked to record how the level of their
      patient's obesity increased the difficulty of specific management items, using a
      Likert scale. Staff also provided recommendations to mitigate the effects of
      obesity for each patient, if applicable. For each management item, body mass
      index (BMI) and management difficulty were correlated (Spearman's rank
      correlation). RESULTS: Seven hundred and fifty patients and their ED carers were
      enrolled. Patient BMI was positively correlated with all aspects of ED clinical
      management examined (correlation coefficient range 0.28-0.57, P < 0.001). BMI
      most strongly correlated with difficulty in finding anatomical landmarks, venous
      pressure measurement, physical examination, patient positioning and procedures
      generally, especially cannulation and venipuncture (coefficient > 0.5, P <
      0.001). Doctors reported more difficulties than nurses and radiographers.
      Generally, management difficulty did not increase until the BMI was in the obese
      or morbidly obese range. Most staff recommendations related to issues of patient
      mobility including equipment, staffing and bariatric devices. CONCLUSION: Patient
      obesity significantly increases the difficulty of ED patient management. Staff
      recommendations to mitigate these effects were few but may inform changes in ED
      practice.

PMID- 20796009
TI  - Short report: What can educators learn from Clever Hans the math horse?

PMID- 20796010
TI  - Tram-related trauma in Melbourne, Victoria.
AB  - OBJECTIVES: To establish the incidence and pattern of injuries in patients
      presenting to hospital with tram-related injuries. METHODS: Data on tram-related
      injury pertaining to 2001-2008 calendar years were extracted from three datasets:
      the population-based Victorian State Trauma Registry for major trauma cases, the
      Victorian Emergency Minimum Dataset for ED presentations and the National
      Coroners' Information System for deaths. Incidence rates adjusted for the
      population of Melbourne, and trends in the incidence of tram-related ED
      presentations and major trauma cases, were analysed and presented as incidence
      rate ratios (IRR). RESULTS: There were 1769 patients who presented to ED after
      trauma related to trams in Melbourne during the study period. Of these, 107
      patients had injuries classified as major trauma. There was a significant
      increase in the rate of ED presentations (IRR 1.03, P = 0.010) with falls (46%)
      the most commonly reported mechanism. Most falls occurred inside the trams. There
      was also a significant increase in the incidence rates of major trauma cases (IRR
      1.12, P = 0.006) with pedestrians accounting for most major trauma cases.
      CONCLUSIONS: Most cases of trauma related to trams have minor injuries and are
      discharged following ED management. Primary prevention of falls in trams and the
      separation of pedestrians from trams are key areas requiring immediate
      improvement. In the face of increasing trauma associated with trams, continuing
      safety surveillance and targeted public safety messages are important to sustain
      trams as safe and effective mode of transport.

PMID- 20796011
TI  - Acute coronary syndrome mimicked by acute cholecystitis.
AB  - Various aetiologies have been reported that cause severe trauma segment and T
      wave abnormalities that are not related to acute coronary syndromes. However, the
      reports of transient ECG abnormalities associated with acute cholecystitis are
      limited in the literature. We describe a 42-year-old man presented with abdominal
      pain and hypertensive episode that developed dynamic ECG changes mimicking acute
      coronary syndrome and was diagnosed acute cholecystitis eventually. Emergency
      physicians should keep in mind dynamic T-wave changes mimicking acute myocardial
      ischaemia in patients with acute cholecystitis.

PMID- 20796012
TI  - Chest pain in pacemaker patients, the answer is not always antiplatelets and
      anticoagulants: a four-case series.
AB  - Chest pain in pacemaker patients can be difficult to evaluate due to alterations
      in QRS and ST segments on the surface ECG. A high prevalence of ischaemic heart
      disease in this population also serves to influence the differential diagnosis.
      We highlight four cases, all with simple yet informative imagery, in an attempt
      to alert clinicians of worrying signs.

PMID- 20796013
TI  - Lumbosacral plexopathy due to a rupture of a common Iliac artery aneurysm.
AB  - We report a case of lumbosacral plexopathy caused by the rupture of a common
      iliac artery aneurysm. The patient presented with sciatic type symptoms of lower
      back pain radiating to his left leg with associated numbness and weakness in the
      L4-S1 distribution. He also had reduced anorectal tone. A CT scan showed a large
      haematoma in the left side of the pelvis from a ruptured 8 cm common iliac artery
      aneurysm. Sciatica is commonly due to a prolapsed intervertebral disc, although
      spinal canal stenosis, spondylolisthesis, piriformis syndrome and spinal tumours
      and other causes need to be considered. This case serves to increase the
      awareness of the possibility of another uncommon cause, especially when
      additional atypical neurological symptoms exist.

PMID- 20796014
TI  - Phenytoin in toxin-induced seizures.

PMID- 20796020
TI  - FMRFamide regulates oscillatory activity of the olfactory center in the slug.
AB  - In the olfactory center of terrestrial animals, changes in the oscillatory
      frequency of the local field potential (LFP) are thought to be involved in
      olfaction-based behavior and olfactory memory. The terrestrial slug Limax has a
      highly developed olfactory center, the procerebrum, in which the LFP
      spontaneously oscillates. Although changes in the oscillatory frequency are
      thought to correspond to the preference for specific odors, our knowledge about
      the mechanism of this frequency regulation is limited. To clarify the mechanism
      of the bidirectional frequency changes in the procerebrum, we focused on the
      neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFamide), which is known to have
      neuromodulatory functions in invertebrate nervous systems. Application of
      FMRFamide decreased the oscillatory frequency via G-protein-mediated cascades.
      Immunohistochemistry showed that FMRFamide-like-immunoreactive neuronal cell
      bodies are located in the cell mass layer of the procerebrum, projecting their
      neurites to the neuropile layers. The procerebrum was shown to also receive
      innervation from other regions of the cerebral ganglion. Furthermore, according
      to their morphological and projection characteristics, FMRFamide-containing
      neurons belong to the subpopulations of both bursting and nonbursting neurons in
      the procerebrum. The mRNA splice variant encoding multiple copies of canonical
      FMRFamide was specifically expressed in the procerebrum. Taking into account
      previous results showing that serotonin increases the oscillatory frequency, our
      results indicate that FMRFamide and serotonin both regulate the LFP frequency but
      in exactly the opposite direction in the olfactory center of the terrestrial
      slug.

PMID- 20796022
TI  - Calcium dependence of the priming, activation and inactivation of ryanodine
      receptors in frog motor nerve terminals.
AB  - We studied the effects of varying extracellular Ca(2+) ([Ca(2+) ](o) ) and Ca(2+)
      channel density and intracellular loading of Ca(2+) chelators on stimulation
      induced rises in intracellular Ca(2+) ([Ca(2+) ](i) ) in frog motor nerve
      terminals with Ca(2+) imaging. The slowly waxing and waning components of rises
      in [Ca(2+) ](i) induced by repetitive tetani were suppressed by blockers of
      Ca(2+) pumps of the endoplasmic reticulum (thapsigargin and cyclopiazonic acid)
      and a blocker of ryanodine receptors [8-(N,N-diethylamino)octyl 3,4,5
      trimethoxybenzoate hydrochloride] without affecting the initial quickly-rising
      component, thus reflecting the priming (and then subsequent rapid activation) and
      inactivation phases of Ca(2+) -induced Ca(2+) release (CICR) from the endoplasmic
      reticulum. A short tetanus-induced rise in [Ca(2+) ](i) was proportional to
      [Ca(2+) ](o) , whereas the component of CICR was non-linearly related to [Ca(2+)
      ](o) with saturation at 0.9 mm. The progressive blockade of Ca(2+) channels by
      omega-conotoxin GVIA caused proportional decreases in CICR and short tetanus
      induced [Ca(2+) ](i) rises. Intracellular loading of BAPTA and EGTA reduced the
      magnitude of CICR as well as short tetanus-induced rises in [Ca(2+) ](i) with a
      greater effect of BAPTA than EGTA on CICR. The time to peak and the half decay
      time of CICR were prolonged by a low [Ca(2+) ](o) or Ca(2+) channel blocker or
      [Ca(2+) ](i) chelators. These results suggest that ryanodine receptors sense the
      high [Ca(2+) ](i) transient following single action potentials for triggering
      CICR, whereas the priming and inactivation processes of CICR sense a slower,
      persisting rise in [Ca(2+) ](i) during and after action potential trains. A model
      is presented that includes CICR activation in elementary units.

PMID- 20796023
TI  - Revisiting Wallace's haunt: coalescent simulations and comparative niche modeling
      reveal historical mechanisms that promoted avian population divergence in the
      Malay Archipelago.
AB  - Sundaland, a biogeographic region of Southeast Asia, is a major biodiversity
      hotspot. However, little is known about the relative importance of Pleistocene
      habitat barriers and rivers in structuring populations and promoting
      diversification here. We sampled 16 lowland rainforest bird species primarily
      from peninsular Malaysia and Borneo to test the long-standing hypothesis that
      animals on different Sundaic landmasses intermixed extensively when lower sea
      levels during the Last Glacial Maximum (LGM) exposed land-bridges. This
      hypothesis was rejected in all but five species through coalescent simulations.
      Furthermore, we detected a range of phylogeographic patterns; Bornean populations
      are often genetically distinct from each other, despite their current habitat
      connectivity. Environmental niche modeling showed that the presence of unsuitable
      habitats between western and eastern Sundaland during the LGM coincided with
      deeper interpopulation genetic divergences. The location of this habitat barrier
      had been hypothesized previously based on other evidence. Paleo-riverine barriers
      are unlikely to have produced such a pattern, but we cannot rule out that they
      acted with habitat changes to impede population exchanges across the Sunda shelf.
      The distinctiveness of northeastern Borneo populations may be underlied by a
      combination of factors such as rivers, LGM expansion of montane forests and other
      aspects of regional physiography.

PMID- 20796021
TI  - Reversible inactivation of the basolateral amygdala, but not the dorsolateral
      caudate putamen, attenuates consolidation of cocaine-cue associative learning in
      a reinstatement model of drug-seeking.
AB  - Previous research has shown that the basolateral amygdala (BLA) mediates stimulus
      reward learning, including drug-cue associations, whereas the dorsolateral
      caudate putamen (dlCPu) primarily mediates stimulus-response (habit) learning.
      Recent evidence has indicated that the dlCPu may be critical in cocaine-seeking
      following extended self-administration, but it remains unknown whether the dlCPu
      plays a role in the early formation of drug-cue associations. The current study
      used a model of Pavlovian learning to compare the roles of the BLA and dlCPu in
      the consolidation of cocaine-cue associations that maintain cocaine-seeking
      during cue-induced reinstatement. Male Sprague-Dawley rats self-administered
      cocaine (0.2 mg/ 50MUL infusion, i.v.) in the absence of cues for 6 days (2
      h/day). Immediately following a single 1-h classical conditioning session in
      which passive cocaine infusions were paired with a light/tone cue, animals
      received bilateral infusions of the GABA receptor agonists, baclofen/muscimol
      (1.0/0.1 mm), or vehicle into the BLA or dlCPu. Following additional cocaine self
      administration (5 days) and subsequent extinction (no cocaine or cues, 7 days),
      the ability of the previously cocaine-paired cues to reinstate cocaine-seeking
      was assessed. Inactivation of the BLA, but not the dlCPu, immediately following
      the classical conditioning session impaired the consolidation of cocaine-cue
      associations as seen by decreased cue-induced reinstatement. These results extend
      previous findings that the BLA mediates the consolidation of learned associations
      that drive cocaine-seeking during subsequent reinstatement and indicate that the
      dlCPu does not play a role during initial stimulus-drug associative learning.

PMID- 20796026
TI  - Control of transferrin expression by beta-amyloid through the CP2 transcription
      factor.
AB  - Accumulation of beta-amyloid protein (Abeta) is one of the most important
      pathological features of Alzheimer's disease. Although Abeta induces
      neurodegeneration in the cortex and hippocampus through several molecular
      mechanisms, few studies have evaluated the modulation of transcription factors
      during Abeta-induced neurotoxicity. Therefore, in this study, we investigated the
      transcriptional activity of transcription factor CP2 in neuronal damage mediated
      by Abeta (Abeta(1-42) and Abeta(25-35) ). An unbiased motif search of the
      transferrin promoter region showed that CP2 binds to the transferrin promoter, an
      iron-regulating protein, and regulates transferrin transcription. Ectopic
      expression of CP2 led to increased transferrin expression at both the mRNA and
      protein levels, whereas knockdown of CP2 down-regulated transferrin mRNA and
      protein expression. Moreover, CP2 trans-activated transcription of a transferrin
      reporter gene. An electrophoretic mobility shift assay and a chromatin
      immunoprecipitation assay showed that CP2 binds to the transferrin promoter
      region. Furthermore, the binding affinity of CP2 to the transferrin promoter was
      regulated by Abeta, as Abeta (Abeta(1-42) and Abeta(25-35) ) markedly increased
      the binding affinity of CP2 for the transferrin promoter. Taken together, these
      results suggest that CP2 contributes to the pathogenesis of Alzheimer's disease
      by inducing transferrin expression via up-regulating its transcription.

PMID- 20796027
TI  - Intermodule cooperativity in the structure and dynamics of consecutive complement
      control modules in human C1r: structural biology.
AB  - The modular C1r protein is the first protease activated in the classical
      complement pathway, a key component of innate immunity. Activation of the
      heteropentameric C1 complex, possibly accompanied by major intersubunit re
      arrangements besides proteolytic cleavage, requires targeted regulation of
      flexibility within the context of the intramolecular and intermolecular
      interaction networks of the complex. In this study, we prepared the two
      complement control protein (CCP) modules, CCP1 and CCP2, of C1r in their free
      form, as well as their tandem-linked construct, CCP1CCP2, to characterize their
      solution structure, conformational dynamics and cooperativity. The structures
      derived from NMR signal dispersion and secondary chemical shifts were in good
      agreement with those obtained by X-ray crystallography. However, successful
      heterologus expression of both the single CCP1 module and the CCP1CCP2 constructs
      required the attachment of the preceding N-terminal module, CUB2, which could
      then be removed to obtain the properly folded proteins. Internal mobility of the
      modules, especially that of CCP1, exhibited considerable changes accompanied by
      interfacial chemical shift alterations upon the attachment of the C-terminal CCP2
      domain. Our NMR data suggest that in terms of folding, stability and dynamics,
      CCP1 is heavily dependent on the presence of its neighboring modules in intact
      C1r. Therefore, CCP1 could be a focal interaction point, capable of transmitting
      information towards its neighboring modules.

PMID- 20796028
TI  - Flexibility and communication within the structure of the Mycobacterium smegmatis
      methionyl-tRNA synthetase.
AB  - Two structures of monomeric methionyl-tRNA synthetase, from Mycobacterium
      smegmatis, in complex with the ligands methionine/adenosine and methionine, were
      analyzed by X-ray crystallography at 2.3 A and at 2.8 A, respectively. The
      structures demonstrated the flexibility of the multidomain enzyme. A new
      conformation of the structure was identified in which the connective peptide
      domain bound more closely to the catalytic domain than described previously. The
      KMSKS(301-305) loop in our structures was in an open and inactive conformation
      that differed from previous structures by a rotation of the loop of about 90
      degrees  around hinges located at Asn297 and Val310. The binding of adenosine to
      the methionyl-tRNA synthetase methionine complex caused a shift in the KMSKS
      domain that brought it closer to the catalytic domain. The potential use of the
      adenosine-binding site for inhibitor binding was evaluated and a potential
      binding site for a specific allosteric inhibitor was identified.

PMID- 20796029
TI  - A structural overview of the PDI family of proteins.
AB  - Protein disulfide isomerases (PDIs) are enzymes that mediate oxidative protein
      folding in the endoplasmic reticulum. Understanding of PDIs has historically been
      hampered by lack of structural information. Over the last several years, partial
      and full-length PDI structures have been solved at an increasing rate. Analysis
      of the structures reveals common features shared by several of the best known PDI
      family members, and also unique features related to substrate and partner binding
      sites. These exciting breakthroughs provide a deeper understanding of the
      mechanisms of oxidative protein folding in cells.

PMID- 20796046
TI  - Comparison of risk factors for contrast-induced acute kidney injury between
      patients with and without diabetes.
AB  - Although it is well known that diabetics are at a higher risk of contrast-induced
      acute kidney injury (CI-AKI) than nondiabetic patients, the reason for this
      discrepancy is not well known. Thus, in this study, we compared the predisposing
      factors for CI-AKI between patients with and without diabetes. We prospectively
      studied 290 consecutive in-hospital patients including 88 diabetics undergoing
      coronary angiography or a percutaneous coronary intervention in Kowsar hospital,
      and we compared risk factors for CI-AKI between diabetic and nondiabetic
      patients. CI-AKI was defined as RIFLE criteria within 48 hours after contrast
      exposure. The incidence of CR-AKI was significantly higher in diabetic patients
      compared with nondiabetics (P<0.05). The incidence of CI-AKI was significantly
      higher in patients with diabetes and left-ventricular ejection fraction <=40%,
      hypercholesterolemia, serum creatinine >=1.1 mg/dL, estimated glomerular
      filtration rate (eGFR) <90 mL/min, Contrast volume >=80 (mL), maximum safe
      contrast volume factor of 1.5, and dehydration, while in nondiabetics, a
      significantly higher incidence of CR-AKI was observed in those with serum
      creatinine >=1.1 mg/dL (P=0.02) and/or eGFR<60 mL/min (P=0.01). Multiple logistic
      regression analysis showed hyperchlosteremia to be the strongest predictor of AKI
      (P=0.01, B:14.5) in diabetics, followed by eGFR<90 (P=0.05, B:12.4) but, in
      nondiabetics, only eGFR<60 predicted the occurrence of CI-AKI (P=0.04, B:2.3). It
      seems that the predisposing factors to CI-AKI differ in diabetics and
      nondiabetics. In patients with diabetes, hypercholesterolemia is the strongest
      predictor of CI-AKI, followed by eGFR and diabetics are at risk for CI-AKI in the
      early stage of chronic kidney disease (stage 2), accounting for the higher
      incidence of CI-AKI in them.

PMID- 20796031
TI  - TIP39 modulates effects of novelty-induced arousal on memory.
AB  - Tuberoinfundibular peptide of 39 residues (TIP39) is a neuropeptide localized to
      neural circuits subserving emotional processing. Recent work showed that mice
      with null mutation for the gene coding TIP39 (TIP39-KO mice) display increased
      susceptibility to environmental provocation. Based on this stressor-dependent
      phenotype, the neuroanatomical distribution of TIP39, and knowledge that novelty
      induced arousal modulates memory functions via noradrenergic activation, we
      hypothesized that exposure to a novel environment differently affects memory
      performance of mice with or without TIP39 signaling, potentially by differences
      in sensitivity of the noradrenergic system. We tested TIP39-KO mice and mice with
      null mutation of its receptor, the parathyroid hormone 2 receptor (PTH2-R), in
      tasks of short-term declarative and social memory (object recognition and social
      recognition tests, respectively), and of working memory (Y-maze test) under
      conditions of novelty-induced arousal or acclimation to the test conditions. Mice
      lacking TIP39 signaling showed memory impairment selectively under conditions of
      novelty-induced arousal. Acute administration of a PTH2-R antagonist in wild-type
      mice had a similar effect. The restoration of memory functions in TIP39-KO mice
      after injection of a beta-adrenoreceptor-blocker, propranolol, suggested
      involvement of the noradrenergic system. Collectively, these results suggest that
      the TIP39/PTH2-R system modulates the effects of novelty exposure on memory
      performance, potentially by acting on noradrenergic signaling.

PMID- 20796030
TI  - Comparative genomics and functional analysis of niche-specific adaptation in
      Pseudomonas putida.
AB  - Pseudomonas putida is a gram-negative rod-shaped gammaproteobacterium that is
      found throughout various environments. Members of the species P. putida show a
      diverse spectrum of metabolic activities, which is indicative of their adaptation
      to various niches, which includes the ability to live in soils and sediments
      contaminated with high concentrations of heavy metals and organic contaminants.
      Pseudomonas putida strains are also found as plant growth-promoting rhizospheric
      and endophytic bacteria. The genome sequences of several P. putida species have
      become available and provide a unique tool to study the specific niche adaptation
      of the various P. putida strains. In this review, we compare the genomes of four
      P. putida strains: the rhizospheric strain KT2440, the endophytic strain W619,
      the aromatic hydrocarbon-degrading strain F1 and the manganese-oxidizing strain
      GB-1. Comparative genomics provided a powerful tool to gain new insights into the
      adaptation of P. putida to specific lifestyles and environmental niches, and
      clearly demonstrated that horizontal gene transfer played a key role in this
      adaptation process, as many of the niche-specific functions were found to be
      encoded on clearly defined genomic islands.

PMID- 20796047
TI  - Interventions to improve hemodialysis adherence: a systematic review of
      randomized-controlled trials.
AB  - Over 485,000 people in the United States have chronic kidney disease, a
      progressive kidney disease that may lead to hemodialysis. Hemodialysis involves a
      complex regimen of treatment, medication, fluid, and diet management. In 2005,
      over 312,000 patients were undergoing hemodialysis in the United States. Dialysis
      nonadherence rates range from 8.5% to 86%. Dialysis therapy treatment
      nonadherence, including treatment, medication, fluid, and diet nonadherence,
      significantly increases the risk of morbidity and mortality. The purpose of this
      paper is to systematically review randomized-controlled trial intervention
      studies designed to increase treatment, medication, fluid, and diet adherence in
      adult hemodialysis patients. A search of Cumulative Index of Nursing and Allied
      Health Literature (CINAHL) (1982 to May 2008), MEDLINE (1950 to May 2008),
      PsycINFO (1806 to May 2008), and all Evidence-Based Medicine (EBM) Reviews
      (Cochran DSR, ACP Journal Club, DARE, and CCTR) was conducted to identify
      randomized-controlled studies that tested the efficacy of interventions to
      improve adherence in adult hemodialysis patients. Eight randomized-controlled
      trials met criteria for inclusion. Six of the 8 studies found statistically
      significant improvement in adherence with the intervention. Of these 6
      intervention studies, all studies had a cognitive component, with 3 studies
      utilizing cognitive/behavioral intervention strategies. Based on this systematic
      review, interventions utilizing a cognitive or cognitive/behavioral component
      appear to show the most promise for future study.

PMID- 20796048
TI  - Accreditation of postgraduate speciality training programmes in Endodontology.
      Minimum criteria for training Specialists in Endodontology within Europe.
AB  - This consensus statement from the European Society of Endodontology (ESE) sets
      out the minimum criteria for training Specialists in Endodontology within Europe.
      The case is made for recognizing Endodontology as a distinctive dental discipline
      throughout Europe. Guidelines are presented on the requirements of a specialist
      and of a specialist training programme in Endodontology. The aims, objectives and
      curriculum content of a specialist training pathway are outlined, with guidelines
      on trainee appraisal, and the expectations of faculty and institutional
      commitment. In publishing these guidelines, the ESE is responding to a public and
      professional need for consistently high standards of training and specialist
      clinical service within Europe.

PMID- 20796049
TI  - Effectiveness of four electronic apex locators to determine distance from the
      apical foramen.
AB  - AIM: To evaluate the accuracy of four electronic apex locators (EAL) in the
      apical region (0-3 mm short of the foramen) and to compare the precision of the
      readings on the display with the real position of the file in the root canal.
      METHODOLOGY: Twenty single-rooted extracted teeth with round root canals were
      used. The canal orifices were preflared, and the length to the major foramen was
      determined visually under a microscope. Canals were enlarged, so that a size 15
      file fitted well inside the canal. Teeth were mounted in acrylic test tubes
      filled with physiologic saline solution. Electronic length was determined in the
      region between the major foramen and 3 mm short of it in 0.5 mm steps with the
      Dentaport ZX, Root ZX mini, Elements Diagnostic Unit and Apex Locator and Raypex
      5 using files of size 10 and size 15. The data were analysed using linear
      regression between true length and EAL reading, Bland-Altman plots and
      nonparametric tests at a significance level of alpha = 0.05. RESULTS: The major
      foramen was detected by all EALs. With a measurement file positioned directly at
      the major foramen, meter readings were equivalent to a position 0.01-0.38 mm
      away. For the Dentaport ZX, a better accuracy using the size 15 file for the area
      0-1.5 mm short of the apex was found. The differences in measurements between the
      two files were smaller for the other EALs. In linear regression, a good linearity
      for Dentaport ZX and Root ZX mini and moderate linearity for Elements Diagnostic
      Unit and Apex Locator and Raypex 5 were found. The slope of the measurement curve
      was too low (0.37-0.57) for the Raypex 5 and almost optimal for the Dentaport ZX
      (1.01-1.05). The Root ZX mini and the Elements Obturation Unit produced lower
      slope values and especially the Elements Obturation Unit revealed much higher SDs
      at the different measurement levels. CONCLUSION: Amongst the four EALs, the
      Dentaport ZX and Root ZX mini had the best agreement between true lengths and
      meter readings. For the Raypex 5, an interpretation of the colour-coded zones as
      distance to the foramen cannot be recommended and might lead to erroneous
      interpretations.

PMID- 20796051
TI  - We need to 'get real' about counterfeit medicine.

PMID- 20796052
TI  - Advocacy and conflict in nursing.

PMID- 20796053
TI  - Legislation is the beginning, not the end.

PMID- 20796057
TI  - Psychological distress and delusional memories after critical care: a literature
      review.
AB  - BACKGROUND: A considerable number of intensive care unit (ICU) survivors report
      delusional memories, which refer to dreams, nightmares, paranoid delusions and
      hallucinations experienced in the ICU. These memories often have a strong
      vividness, long duration and high emotional impact. AIM: The aim of this review
      was to investigate and synthesize published literature about psychological
      distress associated with delusional memories of adult ICU survivors. METHODS:
      Using key terms, a search was conducted in major health care electronic databases
      [Cumulative Index for Nursing and Allied Health Literature (CINAHL), PubMed, Web
      of Science and PsycInfo] focusing on articles published between 1990 and 2009 in
      English-language journals. FINDINGS: Ten articles met the inclusion criteria.
      Recall of delusional memories at various intervals after ICU discharge was
      associated with post-traumatic stress disorder (PTSD)-related symptoms in many
      studies, while associations with other aspects of psychological distress, mainly
      feelings of fear, anxiety and depression, were also reported. Recent studies did
      not seem to confirm the protective role of factual memories. CONCLUSIONS: The
      findings support the association between delusional memories and PTSD-related
      symptoms, but further research is needed to confirm their association with other
      psychological disorders. Development of a safety sense in the ICU can protect
      patients against the emotional impact of both delusional and stressful factual
      ICU memories. Appropriate follow-up of high-risk patients could improve their
      long-term psychological recovery.

PMID- 20796058
TI  - Conflict and professionalism: perceptions among nurses in Saudi Arabia.
AB  - AIM: To examine the relationship between nurses' perceptions of conflict and
      professionalism. BACKGROUND: In Saudi Arabia, health-care sectors are constantly
      undergoing major changes because of social, consumer-related, governmental,
      technological and economic pressures. These changes will influence the nature of
      health-care organizations, such as hospitals' work environment. The ability of
      nurses to practise in a professional manner may be influenced by their work
      environment and conflict level. METHODS: A cross-sectional design was conducted
      in this study. A simple random selection of three health-care sectors in Saudi
      Arabia was performed and 346 nurse managers, as well as bedside nurses
      participated to provide information about conflict levels and professionalism.
      The Perceived Conflict Scale was used to assess the level of conflict, and the
      Valiga Concept of Nursing Scale was used to assess the professionalism perception
      among nurses. RESULTS: The intragroup/other department type of conflict had a
      statistically significant correlation with the perception of professionalism. In
      addition, the findings point to a low perception among the participating nurses
      regarding their professionalism. CONCLUSION: A number of factors might explain
      the low level of perception of professionalism. These relate to the workplace
      itself, as well as to the personal background of the nurses, which includes the
      personal interest in the nursing profession, as well as the family's, society's
      and the consumers' views of the profession. Given the findings of this study,
      nurse managers are encouraged to create a work environment that supports
      professionalism and minimizes conflict.

PMID- 20796059
TI  - Mistrust of academic knowledge among nurses in Slovenia.
AB  - AIM: The paper discusses the negative attitudes of some nursing assistants in
      Slovenia towards higher nursing education and academic (theoretical and research
      based) knowledge. BACKGROUND: The topic is discussed in the context of
      traditional hierarchical and patriarchal relations in the health-care sector,
      professionalization of nursing and the evidence-based debate in nursing. METHODS:
      A secondary analysis of data gathered in 2005 was carried out. The topic of the
      original research was the interprofessional collaboration between medical and
      nursing care professionals in Slovenia. The secondary study looked closely into
      the relations within nursing care. Specifically it focused on the nursing
      assistants' perspective. Five hundred ninety-two answer to two open-end questions
      (307 from nurses and 285 from nursing assistants) and five semi-structured
      interviews (with three nurses and two nursing assistants) were re-analyzed (with
      the new focus), applying inductive qualitative content analysis and the pragmatic
      approach to interpretation. FINDINGS: In nursing assistants' view, the difference
      between themselves and graduate nurses was described in terms of the distinction
      'work-non-work'. Higher education was associated primarily with striving for
      higher social status. Academic knowledge was not perceived to include the right
      competencies for either practising or improving the quality of nursing care.
      CONCLUSIONS: The mistrust of the academic nurse on the part of some nursing
      assistants is interpreted as a barrier to full professionalization of nursing
      care and also interprofessional collaboration in the health-care sector.

PMID- 20796060
TI  - Teaching nursing in a situation of conflict: encounters between Palestinian
      Israeli and Jewish-Israeli nursing students.
AB  - PURPOSE: This research examines the ways Palestinian-Israeli and Jewish-Israeli
      nursing students, who study together in one group in an academic school of
      nursing situated in northern Israel, perceive each other and the relationships
      among them. DESIGN: The study is based on semi-structured interviews with
      undergraduate students. The cohort consists of 46 students, 20 of whom
      participated in the study. FINDINGS: The students perceive themselves as divided
      into two separate groups according to nationality. Cooperation between the groups
      related to their study duties is described as generally satisfying, but little
      expressive communication and scarce social relations occur across these two
      groups. Students provided their perceptions of 'the others' to explain this
      social distance. IMPLICATIONS: We discuss the challenges of the situation for
      nursing educators and some strategies for coping with these challenges.

PMID- 20796061
TI  - Operating room nurses' perceptions of the effects of physician-perpetrated abuse.
AB  - BACKGROUND: Operating room (OR) nurses experience abuse perpetrated by
      physicians; however, little research has been conducted to examine nurses'
      perceptions of the effects of such abuse. AIMS: The aim of this research was to
      understand participants' perceptions of physician-perpetrated abuse on their
      health and ability to provide patient care. MATERIALS/METHODS: In this
      qualitative descriptive study, ten operating room nurses working in Eastern
      Canada participated in open-ended, individual audiotaped interviews that were
      transcribed for analysis using Boyatzis' method for code development. RESULTS:
      Three categories of factors contributing to abuse were developed. The first,
      culture of the OR, included environment and hierarchy. The second, catalysts of
      abuse, included nurses' positions and experience as well as non-nurse factors
      such as resources and interpersonal relationships among physicians. The third
      category, perceived effects, included psychological, physical and social health
      consequences for nurses. Effects on patient care consisted of safety and
      potential challenges to access. DISCUSSION: Nursing practice implications
      included mentoring, support and accountability for action. Educational
      implications related to interdisciplinary education and increased education on
      communication, assertiveness, and awareness of abuse. Implications for research
      included studying perceptions of other health-care providers including
      physicians, studying recruitment and retention in relation to abuse, and studying
      other abuse in health care such as horizontal violence. CONCLUSION: We suggest a
      proactive approach for empowering OR nurses to address abuse and an increased
      focus on interdisciplinary roles.

PMID- 20796062
TI  - Mobbing against nurses in the workplace in Turkey.
AB  - AIM: The aim of the study was to determine whether the nurses have been exposed
      to mobbing or not, and to reveal the causes of the mobbing between 3 November
      2008 and 31 December 2008. METHODS: This research was a mixed method study
      involving survey and focus group interviews. The sample was calculated using
      sample calculation formula, and 206 nurses were included in the survey study.
      Four focus group interviews were later carried out with 16 nurses. The survey
      method and semi-structured question form were used to collect data. The
      percentage and chi-square were used to evaluate the quantitative data, and for
      the analysis of the qualitative data, descriptive analyses were made through
      direct quotations from the nurses' statements. FINDINGS: According to the mobbing
      scale, 9.7% of the nurses had been exposed to mobbing, but according to their own
      declarations, 33% had been exposed. Some of the nurses (25.2%) who expressed that
      they had been exposed to mobbing reported that the executor of mobbing was the
      head nurse and 9.2% said that the reason for mobbing was 'communication
      problems'. Nurses under 25 years of age and those who work in intensive care
      units are apparently exposed to mobbing more frequently than others (P<0.05).
      CONCLUSIONS: It is suggested that head nurses' mobbing behaviours should be
      determined and they should be educated about leadership. Nurses should be
      educated about assertiveness to prevent mobbing. The necessary measures should be
      adopted to solve the 'communication problems', which are shown as a major reason
      for mobbing.

PMID- 20796063
TI  - Nurses in the workplace: expectations and needs.
AB  - BACKGROUND: It is important to understand nurses' attitudes toward their work
      environment. Prior studies in this area have been conducted. The interest was to
      identify a relative assessment of workplace challenges by studying nurses within
      developed and developing economies. METHOD: A representative survey of 2203
      nurses in 11 countries was conducted via a structured survey. Data from open
      ended questions were content analysed and grouped thematically. The overall
      margin of error is +/-2.1% and +/-6.9% for country level results. RESULTS: Key
      findings included that 92% of nurses say they face time constraints and 96% say
      that spending more time with individual patients would have a significant impact
      on patient health. Forty-six per cent of nurses say their workload is worse today
      than it was 5 years ago. While only 53% of nurses say it is very likely they will
      be practising nursing in 5 years, national differences existed. Statistically
      significant parameters influencing the likelihood to stay in nursing included
      having greater independence and control over their practice area, sufficient
      staff, greater involvement in decisions impacting their work and patient care,
      and improved work-life balance. CONCLUSIONS: There is agreement across the
      surveyed countries regarding the existence of high workloads that are
      contributing to time constraints and the belief that patient outcomes are
      significantly impacted. These conditions contribute to nurses' lack of firm
      commitment to their profession. The systemic changes required to deliver quality
      health care to patients require these challenges to be addressed.

PMID- 20796064
TI  - Environments for nursing scholarship and journal impact factor in five countries.
AB  - BACKGROUND: Universities worldwide are seeking objective measures for the
      assessment of their faculties' research products to evaluate them and to attain
      prestige. Despite concerns, the impact factors (IF) of journals where faculties
      publish have been adopted. RESEARCH OBJECTIVE: The study aims to explore
      conditions created within five countries as a result of policies requiring or not
      requiring faculty to publish in high IF journals, and the extent to which these
      facilitated or hindered the development of nursing science. DESIGN: The design
      was a multiple case study of Brazil, Taiwan, Thailand (with IF policies, Group
      A), United Kingdom and the United States (no IF policies, Group B). Key
      informants from each country were identified to assist in subject recruitment.
      METHODS: A questionnaire was developed for data collection. The study was
      approved by a human subject review committee. Five faculty members of senior rank
      from each country participated. All communication occurred electronically.
      FINDINGS: Groups A and B countries differed on who used the policy and the
      purposes for which it was used. There were both similarities and differences
      across the five countries with respect to hurdles, scholar behaviour, publishing
      locally vs. internationally, views of their science, steps taken to
      internationalize their journals. CONCLUSIONS: In group A countries, Taiwan seemed
      most successful in developing its scholarship. Group B countries have continued
      their scientific progress without such policies. IF policies were not necessary
      motivators of scholarship; factors such as qualified nurse scientists, the
      resource base in the country, may be critical factors in supporting science
      development.

PMID- 20796065
TI  - A Canada-Bangladesh partnership for nurse education: case study.
AB  - AIM: To describe the lessons learned from a partnership in nurse education
      between a Bangladesh university and a group of Canadian volunteers. BACKGROUND:
      In the host country, nursing enjoys low status and pay, which adversely affect
      professional standards. METHOD: The paper describes implementation details of
      training a core of nurses to international standards, using limited resources.
      The first cohort received their Bachelor of Nursing degrees in 2009. OUTCOMES:
      The Bangladeshi partners benefit from access to up-to-date curriculum materials,
      current clinical expertise, and interaction with visiting faculty and students.
      The Canadian nursing instructors enjoy professional development opportunities;
      visiting Canadian students gain exposure to a practice setting in a low-income
      country. LESSONS LEARNED: These include the importance of (1) integrating nurse
      training with a general university able to provide core courses (e.g. English as
      second language, computer training), (2) countering the low status of nursing and
      inculcating a caring attitude among students, and (3) instilling critical
      thinking as opposed to rote learning. Next, the following were identified:
      mechanisms to support networking in the local health system, sharing of resources
      (e.g. electronic course material adapted to host country context), and assuring
      programme quality. IMPLICATIONS FOR PRACTICE: The paper will be of interest to
      those concerned with nurse education and human resource development in less
      developed countries.

PMID- 20796066
TI  - The establishment of an integrated skills training centre for undergraduate
      nursing education.
AB  - AIM: This paper details the experience of establishing an integrated skills
      training centre for use in undergraduate nursing education in The Open University
      of Hong Kong. BACKGROUND: Skills training is an essential element in
      undergraduate nursing education. Owing to the increasing complexity of the health
      care system and patient health needs, undergraduate nursing students should be
      well prepared for integrated skills competency, critical thinking and rapid
      decision-making. To achieve this goal, the use of simulation as a skills training
      tool is being recommended. CONCLUSION: The Clinical Nursing Education Centre is
      established. It adopts simulation as a teaching and learning tool. It has four
      specific education units, namely: (1) clinical simulation education unit, (2)
      virtual reality education unit, (3) nursing skills education unit, and (4)
      Chinese medicinal education unit. These units are specifically designed for the
      teaching and learning of nursing skills related to general, mental and Chinese
      medicinal nursing from elementary to advanced level. Experiences pertaining to
      the conceptualization, exploration and actualization phases of the establishment
      are presented. Details of the structure and specific functions of the centre are
      also illustrated. Finally, there is discussion on the challenges encountered
      during the establishment process and how they were overcome.

PMID- 20796067
TI  - Hepatitis B and C seropositivity among nursing students at a Turkish university.
AB  - BACKGROUND: Viral hepatitis infections are major health problems, which are
      especially prevalent in developing countries. In particular, health care workers
      are at high risk for contracting viral hepatitis. Therefore, preventive measures
      to minimize occupational exposure to blood borne pathogens are needed to protect
      both health care workers and nursing students. OBJECTIVES: To determine the
      prevalence of Hepatitis B and C infections and risk factors among nursing
      students. METHODS: Venous bloods were obtained from nursing students and were
      serologically tested using the ELISA method. A questionnaire form was also used
      to obtain data related to demographic and socio-economic characteristics of the
      participants. RESULTS: 0.7% of the nursing students were serologically positive
      for HBsAg, 17.0% for Anti-HBs and 7.5% were positive for Anti-HBc (IgG). No
      statistical relationship was determined between all independent variables and the
      results of serologic tests.

PMID- 20796068
TI  - Undergraduate nursing students' attitudes towards organ donation: a survey in an
      Italian university.
AB  - AIMS: To examine undergraduate nursing students' attitudes towards organ donation
      and to determine whether or not attitudes were related to the students' education
      and training. BACKGROUND: Nurses' knowledge and personal opinion can influence
      patient's willingness to donate organs or to hold an organ donor card. It is
      unclear how Italy's future nurses view organ donation. METHODS: The study's
      source population consisted of third-year undergraduate nursing students enrolled
      in seven nursing schools from an Italian university during 2008. Respondents
      completed self-administered quantitative questionnaire with 61 questions,
      including the Organ Donation Attitude Scale. FINDINGS: Of the 378 students
      contacted, 183 (48%) completed all survey questions; 140 were females (76.5%) and
      the mean age of students was 25. The median score of students' attitude scores
      towards organ donation was 151 (the attitude is positive when the score is higher
      than 161). No significant correlations were found to exist between organ-donation
      attitude and sex, age, clinical practice in hospitals with a transplant unit,
      nursing care to patients waiting for a transplant or dialysis patients. Only 16%
      of the students had previously signed a donor card consenting to their own organ
      donation. The study revealed that doubts about transplantable organs still exist
      within the student body. CONCLUSIONS: This study highlighted that students'
      awareness of organ donation was not adequate and that attitude levels were lower
      than in other countries. If these future workers would receive adequate training,
      they could promote organ donation to the general public and to other hospital
      personnel.

PMID- 20796069
TI  - Family planning practice and related factors of married women in Ethiopia.
AB  - BACKGROUND: The family planning (FP) practice rate of Ethiopian women of
      reproductive age is lower than in most other sub-Saharan African countries. AIM:
      To examine the status of FP practice and identify intrapersonal, interpersonal
      and community factors associated with FP practice among married Ethiopian women
      in a rural area. METHODS: A cross-sectional survey was conducted with a
      convenient sample of 193 married women of reproductive age. A structured
      questionnaire, which was modified based on the Ethiopian Demographic Health
      Survey, was used. Multiple logistic regression analysis was conducted to identify
      factors associated with FP practice at three levels: intrapersonal, interpersonal
      and community. RESULTS: Almost 67% of women were currently using at least one FP
      method and most women obtained FP methods from the public health sector. Short
      term methods such as pills and injections were most commonly used. FP practice
      was significantly associated with willingness to use long-term or permanent FP
      methods in future and spousal discussion about FP. CONCLUSIONS: Both
      intrapersonal and interpersonal factors were related to FP practice. Community
      factors, however, need to be further assessed using various methods to plan a
      comprehensive and more culturally acceptable community-based FP program. Caution
      is needed to generalize the findings because of the convenient sample, but
      community-based FP programs emphasizing long-term or permanent methods and male
      involvement in FP counseling would be successful strategies to increase FP
      practice. IMPLICATIONS FOR NURSING PRACTICE: Nurses and midwives need to be
      trained to provide knowledge and skills for long-term or permanent FP methods for
      service quality.

PMID- 20796070
TI  - Traditional practices used by infertile women in Turkey.
AB  - BACKGROUND: Numerous traditional methods are used in the treatment of infertility
      around the world. AIM: To identify the traditional practices of infertile women
      using one clinic in Ankara, Turkey. DESIGN AND METHODS: The population comprised
      all women (5700) who attended one infertility outpatient clinic in 2007. The
      sample was calculated using sample calculation formula and 410 women were
      included in the study. The survey method was used for data collection. FINDINGS:
      Of the responding women, 27.3% had tried a traditional practice, and 67.8% who
      tried traditional practices used an herbal mixture. The reason for the women's
      use of a traditional practice was 'hope' (66.9%), and 15.2% of them had
      experienced an adverse effect related with traditional practice. Maternal
      education level, perceived economic status, duration of marriage all
      significantly affected the use of traditional practices (P<0.05). The women who
      had received unsuccessful medical treatment for infertility and who had
      experienced side effects after medical treatment had a higher rate of use of
      traditional practice (P<0.05). CONCLUSIONS: Almost one in three of the women who
      responded to the questionnaire had tried traditional methods, and some
      experienced adverse effects related to the practice. For couples with infertility
      problems, educational programmes and consultation services should be organized
      with respect to their traditional culture. Women should be informed about the
      hazards of traditional practices and avoidance of harmful practices, and
      continuous emotional support must be provided for infertile couples. In the
      future, nursing staff should play a much larger role in these supportive
      services.

PMID- 20796071
TI  - Smoking during pregnancy: analysis of influencing factors using the Theory of
      Planned Behaviour.
AB  - AIM: To investigate factors affecting women's intention to smoke during
      pregnancy. DESIGN: A descriptive, correlational, cross-sectional study, employing
      the Theory of Planned Behaviour (TPB). METHODS: A questionnaire that was
      constructed based on a literature review of research on smoking during pregnancy
      and on the TPB was administered to 201 Israeli female smokers aged 19-46.
      Descriptive, correlational and linear regression statistics were calculated.
      RESULTS: Behavioural attitudes (women's total appraisal of smoking during
      pregnancy), subjective norms (women's perception of the opinion of significant
      others regarding the specific behaviour) and perceived behavioural control
      (women's total appraisal of their control of the behaviour and perceived ease or
      difficulty of quitting smoking during pregnancy) were found to predict women's
      intention to smoke during pregnancy. CONCLUSIONS: Nursing interventions guided by
      the TPB constructs may help Israeli women quit smoking during pregnancy and
      reduce the prevalence of smoking during pregnancy.

PMID- 20796072
TI  - Turkish women's perceptions of antenatal education.
AB  - BACKGROUND: Antenatal education is considered essential for expectant women.
      Although there are a number of studies on the effects of antenatal education,
      there are few studies featuring substantial evidence in this area. For this
      reason, the benefits have not been clearly defined. AIM: To describe women's
      perceptions of the effectiveness of antenatal education on pregnancy, childbirth
      and the post-partum period, and also to describe their impressions on the type of
      education received. METHODS: A qualitative approach was used. The study featured
      15 primipara women who had attended antenatal education. Data were gathered
      through semi-structured interviews and analysed using the content analysis
      method. FINDINGS: The results of this study showed that education provided a
      basis of knowledge about pregnancy, childbirth and the post-partum period. It was
      found that education could have positive effects on pregnancy, childbirth,
      breastfeeding, motherhood and infant care, and that it could at the same time
      have a positive or negative effect on fear of childbirth. Although different
      advantages were found to be perceived in both individual and group education, it
      was discovered that the study participants were much more satisfied with
      attending group sessions. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE:
      Antenatal education should be planned in such a way that its content and
      methodology do not increase fear. When the lower costs incurred and the higher
      satisfaction level attained are considered, group education appears to be the
      type of antenatal education that should be preferred.

PMID- 20796073
TI  - Comparison of grass haylage digestibility and metabolic plasma profile in
      Icelandic and Standardbred horses.
AB  - The aim of the present study was to compare digestibility and metabolic response
      in Icelandic and Standardbred horses fed two grass haylages harvested at
      different stages of maturity. Six horses of each breed were used in a 24-day
      change-over design. A total collection of faeces was made on days 15-17 and 22
      24. Blood samples were collected on day 24 of each period and analysed for total
      plasma protein (TPP), plasma urea, non-esterified fatty acids, cortisol and
      insulin concentration. There were no differences in digestibility coefficients of
      crude protein, neutral detergent fibre or energy between breeds but organic
      matter digestibility was higher in the Standardbred horses. On both haylages, the
      Icelandic horses gained weight whereas the Standardbred horses lost weight. The
      Icelandic horses had higher TPP, plasma insulin and lower plasma urea
      concentrations. Our results indicate that the Icelandic horse may be more prone
      to maintain positive energy balance in relation to the Standardbred horse, but
      there were no indication of a better digestive capacity in the Icelandic horses.

PMID- 20796074
TI  - Effect of thermal stress, restricted feeding and combined stresses (thermal
      stress and restricted feeding) on growth and plasma reproductive hormone levels
      of Malpura ewes under semi-arid tropical environment.
AB  - A study was conducted to assess the effect of thermal, nutritional and combined
      stresses (thermal and nutritional) on the growth, oestradiol and progesterone
      levels during oestrus cycles in Malpura ewes. Twenty-eight adult Malpura ewes
      were used in the present study. The ewes were randomly allocated into four
      groups, viz., GI (n=7; control), GII (n=7; thermal stress), GIII (n=7; restricted
      feeding) and GIV (n=7; combined stress). The animals were stall fed with a diet
      consisting of 60% roughage and 40% concentrate. GI and GII ewes were provided
      with ad libitum feeding while GIII and GIV ewes were provided with restricted
      feed (30% intake of GI and GII ewes) to induce nutritional insufficiency. GII and
      GIV ewes were kept in climatic chamber at 40 degrees C and 55% RH for 6 h a day
      between 10:00 and 16:00 hours to induce thermal stress for a period of two
      oestrous cycles. Parameters studied were body weight, oestrus incidences, plasma
      oestradiol 17-beta, plasma progesterone, conception rate, gestation period,
      lambing rate, and birth weight of lambs. The results indicate that combined
      stress significantly (p<0.05) reduced body weight, oestrus duration, birth weight
      of lambs, and oestradiol 17-beta whereas significantly (p < 0.05) increased
      oestrus cycle length and progesterone. Furthermore, the results reveal that on
      comparative basis, ewes were able to better adapt in terms of growth and
      reproduction to restricted feeding than thermal stress. However, when restricted
      feeding was coupled with thermal stress it had significant (p<0.05) influence on
      body weight, average daily gain, oestradiol 17-beta and progesterone
      concentrations. This showed that combined stress were more detrimental for these
      reproductive hormones in Malpura ewes under a hot semi-arid environment.

PMID- 20796075
TI  - Dietary impact on circulating glucose profiles in the white rhinoceros.
AB  - Excess dietary glucose may be a factor in several captive wildlife diseases and
      reproductive abnormalities. The first step in understanding the health
      consequences of diets high in glucose is to characterize how dietary glucose
      concentrations change circulating glucose profiles. We adapted the glycemic index
      approach to detect differences in blood glucose concentrations in white rhinos in
      response to different meals. Six white rhinos were fasted overnight then randomly
      assigned to be fed 5 kg of grass hay and one of five meals varying in digestible
      energy (DE) availability and source (10% DE glucose, 5% DE glucose, 10% DE
      pelleted horse feed, 10% DE lucerne hay, 10% DE grass hay). After eating, the
      blood glucose response peaked 45-90 min later and remained elevated up to 180
      min. Area under the curve results demonstrated that the blood glucose response
      was not different between diets. However, at 90 min, serum glucose levels in
      rhinos eating the 10% lucerne hay diet were significantly lower than the 5%
      glucose and 10% glucose diets but not the 10% pellet nor 10% grass hay diets. The
      changes in blood glucose responses to different diets were similar in magnitude
      to reported domestic horse profiles but are higher than predicted by allometric
      scaling. We conclude that the grass hay, lucerne hay and low glycemic index horse
      pellets fed in this study resulted in similar blood glucose responses in white
      rhinos. The validation of the methodology used in this study is a first step
      towards elucidating the relationship between glucose, obesity, health and
      reproduction in rhinos.

PMID- 20796076
TI  - Effect of feeding rumen protected rice bran on calcium homeostasis of non
      lactating multiparous cows.
AB  - Milk fever in dairy cows can be prevented by activating Ca homeostasis before
      calving. Homeostatic adaptation can be achieved by reducing dietary Ca
      availability. Formaldehyde-treated rice bran was studied to supply rumen
      protected phytic acid to reduce Ca availability. Twelve multiparous dry cows were
      used in a 3*3 Latin square change-over design with 5-day periods to test three
      dietary treatments. Diets consisted of a forage mix (maize silage, grass silage
      and hay), being 77% of ration dry matter, supplemented with three concentrates:
      Control (no formaldehyde-treated rice bran), T1 (100% formaldehyde-treated rice
      bran) and T2 (99.5% formaldehyde-treated rice bran with 0.6% Ca carbonate, to
      equal Ca content of Control). Dietary treatments did not affect urine pH (8.14,
      8.13 and 8.11 for Control, T1 and T2 respectively) or dry matter intake (13.9,
      13.7 and 13.8 kg for Control, T1 and T2 respectively). Including formaldehyde
      treated rice bran in the diet resulted in lower urinary Ca/creatinine ratio
      (0.970, 0.457 and 0.618 for Control, T1 and T2 respectively). A sudden increase
      of urinary Ca excretion took place after withdrawal of T1 and T2 at introduction
      of Control, peaking on the first day and coming back down progressively in the
      second and third days. Peak was greatest after T1 and was not observed in
      transitions between rice bran treatments. This is understood as indirect evidence
      of activation of intestinal Ca absorption during formaldehyde-treated rice bran
      feeding, because renal adaptations to changes in blood Ca clearance are immediate
      and intestinal adaptations delay 2 days. It was concluded that including
      formaldehyde-treated rice bran in rations before calving may represent a dietary
      strategy to prevent milk fever without reducing dry matter intake.

PMID- 20796077
TI  - Fatty acid and energy metabolism in broiler chickens fed diets containing either
      beef tallow or an oil blend.
AB  - The hypothesis tested was that the feeding of n-6 polyunsaturated fatty acids
      (PUFA) results in more whole-body fatty acid oxidation than the feeding of
      saturated fatty acids (SFA). It was reasoned that the increased fatty acid
      oxidation would be associated with enhanced whole-body energy expenditure and
      stimulated de novo fatty acid synthesis. To put the hypothesis to the test,
      broiler chickens were fed diets containing either beef tallow as source of SFA or
      an oil blend as source of n-6 PUFA. The broilers either had free access to their
      diet or were fed a restricted amount. Seven-day-old, male broiler chickens were
      used; they were kept individually in cages from 1 to 4 weeks of age. In the birds
      fed ad libitum, the n-6 PUFA diet reduced average daily feed intake (ADFI), but
      did not significantly affect average daily weight gain (ADG) and the
      feed:conversion ratio (FCR). The lower ADFI on the n-6 PUFA diet was associated
      with a higher apparent digestibility of total fatty acids. The ratio of
      deposition in the body to intake of digestible total PUFA, which reflected n-6
      PUFA, was significantly decreased by the n-6 PUFA diet, pointing at
      preferentially increased n-6 PUFA oxidation on the n-6 PUFA diet. The ratio for n
      9 monounsaturated fatty acids (MUFA) was higher than 1.0, which agrees with net
      de novo synthesis, but the n-6 PUFA diet induced a lower value than did the SFA
      diet. Feeding either the n-6 PUFA or SFA diet did not influence energy
      expenditure expressed as percentage of energy intake. This study supports the
      idea that dietary n-6 PUFA instead of SFA are preferentially oxidized, but no
      proof was obtained for enhanced energy expenditure and contrary to the hypothesis
      put forward, the n-6 PUFA diet depressed de-novo fatty acid synthesis.

PMID- 20796078
TI  - Inter-related effects of dietary fat and protein level on growth performance in
      rabbits.
AB  - Isoenergetic substitution of dietary corn oil for dietary carbohydrates enhances
      growth in rabbits. It was hypothesized that identical amounts of metabolizable
      energy in the form of corn oil are more effective than those of carbohydrates in
      reducing protein catabolism and thus sparing it for growth, which would imply
      that the fat effect is greater on a marginal than normal protein diet. Young
      growing rabbits were fed semi-purified diets either relatively high (21.6 energy
      % protein) or low in casein (13.0 energy % protein) to which extra corn oil (21.1
      instead of 5.3 energy %) was added at the expense of an isoenergetic amount of
      corn starch and dextrose. The addition of corn oil to the diet with 21.6 energy %
      protein indeed increased weight gain, but the addition to the diet with 13.0
      energy % protein left weight gain unchanged. These results refute our hypothesis,
      because the low-protein intake was not limiting growth. The enrichment of the
      high-protein diet with extra corn oil did not affect nitrogen retention, whereas
      urinary nitrogen excretion was increased. These observations also are at variance
      with the idea that additional fat would spare nitrogen for growth.

PMID- 20796079
TI  - Administration of RRR-alpha-tocopherol to pregnant mares stimulates maternal IgG
      and IgM production in colostrum and enhances vitamin E and IgM status in foals.
AB  - This study assessed the effect of a vitamin E supplement given to pregnant mares
      on immunoglobulins (Ig) levels in foals. In addition, the fatty acid (FA) content
      and composition of the mares' milk was assessed. Milk alpha-tocopherol
      concentrations were compared between pregnant Danish Warmblood mares (n = 17)
      given a daily oral supplement of 2500 international units (IU) RRR-alpha
      tocopherol in the last 4 weeks of pregnancy and a group of unsupplemented mares
      (n = 17) receiving 170-320 IU vitamin E daily originating from the feed. Milk
      alpha-tocopherol was higher in supplemented mares (36.7, 12.4 and 9.8 MUmol/l
      respectively) in relation to control mares (13.1, 6.4 and 5.8 MUmol/l on days 1,
      2 and 3 respectively; p < 0.001). Milk IgG was higher on days 2 and 3 post-partum
      (PP) in supplemented mares (1.03 and 0.73 mg/ml respectively) in relation to
      control mares (0.79 and 0.56 mg/ml respectively; p < 0.05). Milk IgM was higher
      on days 2 and 3 post-partum (PP) in supplemented mares (0.19 and 0.17 mg/ml) in
      relation to control mares (0.13 and 0.11 mg/ml respectively; p < 0.05). Plasma
      alpha-tocopherol in foals was higher from supplemented mares on days 1, 2 and 3
      (5.7, 14.8 and 19.2 MUmol/l respectively) in relation to foals from control mares
      (3.6, 6.1 and 7.6 respectively; p < 0.001). Foal plasma IgM was higher from
      supplemented mares on day 3 (0.50 mg/ml) in relation to foals from control mares
      (0.32 mg/ml; p < 0.001). The total FA content in milk was highest on day 1 (21.6
      g FA/kg milk) in relation to days 2 and 3 (13.6 and 13.5 g FA/kg milk
      respectively; p < 0.001). In conclusion, a daily oral supplement of 2500 IU RRR
      alpha-tocopherol increased alpha-tocopherol content in mare milk and foal plasma,
      IgG and IgM in mare milk and IgM in foal plasma.

PMID- 20796080
TI  - Effect of high oral doses of nitrate on salivary recirculation of nitrates and
      nitrites and on bacterial diversity in the saliva of young pigs.
AB  - Ingested nitrate is absorbed in the small intestine, recirculated into the saliva
      and reduced to nitrite by oral bacteria. In pigs receiving a moderate dietary
      addition of nitrate, the recirculation into the saliva is modest, so we aimed to
      assess the effect of higher nitrate doses to find out how the animal reacts to
      this new situation and to evaluate if a higher nitrate level could enhance the
      nitrate reduction process, improving the nitrite production Trial 1. Six piglets
      received 100 g of a commercial diet with 2.45% KNO(3) . In relation to baseline
      values, nitrate in blood serum and saliva increased 15 times, and declined after
      6 h vs. 2 h. Salivary nitrite increased seven times after the addition and
      declined after 6 h vs. 2 h. Trial 2. Six piglets were fed a diet with or without
      1.22% KNO(3) for 2 weeks. Salivary nitrate and nitrite increased with the
      addition of KNO3: nitrate increased from d0 to the end of the trial, nitrite
      increased 15 times after 1 week, but decreased after 2 weeks to 4.5-fold the
      control. After 2 weeks, nitrate reduced Shan diversity index of salivary
      microbiota. The present results indicate that the long exposure to high
      quantities of nitrates impairs the oral reduction of nitrate to nitrite and
      engenders a reduction of the mouth's microbiota diversity.

PMID- 20796081
TI  - Effect of dietary antioxidant supplementation on the oxidative status of plasma
      in broilers.
AB  - In this study, the effect of dietary antioxidants on the plasma oxidative status
      of growing birds fed a diet rich in polyunsaturated fatty acids was investigated.
      One-day-old broilers were fed for 42 days a diet containing 4% linseed oil and
      supplemented with single plant extracts rich in antioxidants (natural
      tocopherols, rosemary, grape seed, green tea, tomato) or a combination of some of
      these plant extracts, in two different total doses (100 and 200 mg product/kg
      feed). A diet with synthetic antioxidants with and without alpha-tocopheryl
      acetate (200 mg/kg feed) were also included. The plasma oxidative status was
      evaluated measuring the ferric reducing ability of plasma (FRAP), the superoxide
      dismutase (SOD) and glutathione peroxidase (GSH-Px) activity. Lipid peroxidation
      was measured by thiobarbituric acid-reactive substances (TBARS). No significant
      effect of the dietary treatments was observed for FRAP as well as for TBARS.
      However, diet affected GSH-Px activity (p = 0.002) and a trend for an effect on
      SOD activity was observed (p=0.084). A higher GSH-Px activity was found for 200
      mg/kg tomato extract and natural alpha-tocopherol in relation to the
      corresponding 100 mg/kg treatment, and the lowest GSH-Px activity was measured
      for the synthetic antioxidants treatment. The lowest and highest SOD activity
      were found for the 200. and 100 mg/kg treatment with tomato extract respectively.
      In conclusion, the oxidative status and lipid oxidation of plasma in broilers was
      not affected by feeding natural antioxidant extracts at the doses in the present
      study, but some changes in antioxidant enzyme activities were observed, of which
      the implication remains to be elucidated.

PMID- 20796082
TI  - Effect of feeding rumen-protected rice bran on mineral status of non-lactating
      dairy heifers.
AB  - Adapting Ca homeostasis of dairy cows before calving can prevent milk fever. Rice
      bran, treated with formaldehyde to prevent ruminal degradation of phytic acid,
      was fed to heifers to study its effect on Ca homeostasis. For 3 weeks 18 heifers
      were supplemented 3 kg of two feeds: placebo (PF) and rice bran (RBF), defining
      three treatments: control (CRT), low dose (LD) and high dose (HD). In weeks 1 and
      3, all animals received 3 kg of PF and in week 2: CRT received 3 kg of PF, LD
      received 1.5 kg of PF and 1.5 kg of RBF and HD received 3 kg of RBF. Treatments
      did not affect dry matter intake (DMI). Feed intakes and growth rates indicated
      that all heifers had nutritional requirements that exceeded their Ca intakes.
      Serum Ca, urinary Ca, calcitriol or hydroxyproline remained unaffected. Urinary
      Ca was consistently low indicating high renal Ca reabsorption, which is
      indicative of insufficient Ca supply. Rice bran feed influenced P, Mg and Zn
      intakes and serum and urine presence of these minerals. Most heifers already
      presented an upregulated Ca metabolism, being inadequate to study adaptive
      changes in Ca homeostasis of multiparous dry cows. This metabolic difference can
      be explanatory to the very low susceptibility of heifers to milk fever, further
      supporting the induction of homeostatic adaptation before calving to prevent milk
      fever. Rice bran feed did not reduce DMI, and was not detrimental to P, Mg or Zn
      status.

PMID- 20796084
TI  - Hybrid cardiovascular suite: the operating room of the future.
AB  - The evolving specialty of cardiovascular hybrid surgery that involves the
      integration of advanced interventional techniques into cardiovascular surgery
      requires sophisticated angiographic imaging capabilities in the operating room
      (hybrid suite). This new operating-room concept enables new cardiac-surgery
      therapies and will play a vital role for the advancement of minimally invasive
      cardiovascular surgery. Careful planning and professional expertise is a key
      factor for every hybrid room project.

PMID- 20796085
TI  - Calcified noncoronary sinus of valsalva aneurysm.

PMID- 20796083
TI  - Biochemical and epigenetic changes in phytoplasma-recovered periwinkle after
      indole-3-butyric acid treatment.
AB  - AIM: To elucidate the possible mechanism of phytoplasma elimination from
      periwinkle shoots caused by indole-3-butyric acid (IBA) treatment. METHODS AND
      RESULTS: It has been shown that a transfer of in vitro-grown phytoplasma-infected
      Catharanthus roseus (periwinkle) plantlets from medium supplemented with 6
      benzylaminopurine (BA) to one supplemented with IBA can induce remission of
      symptoms and even permanent elimination of 'Candidatus Phytoplasma asteris'
      reference strain HYDB. Endogenous auxin levels and general methylation levels in
      noninfected periwinkles, periwinkles infected with two 'Candidatus Phytoplasma'
      species and phytoplasma-recovered periwinkles were measured and compared. After
      the transfer from cytokinin- to auxin-containing media, healthy shoots maintained
      their phenotype, methylation levels and hormone concentrations. Phytoplasma
      infection caused a change in the endogenous indole-3-acetic acid to IBA ratio in
      periwinkle shoots infected with two 'Candidatus Phytoplasma' species, but general
      methylation was significantly changed only in shoots infected with 'Ca. P.
      asteris', which resulted in the only phytoplasma species eliminated from shoots
      after transfer to IBA-containing medium. Both phytoplasma infection and treatment
      with plant growth regulators influenced callose deposition in phloem tissue,
      concentrations of photosynthetic pigments and soluble proteins, H(2) O(2) levels
      and activities of catalase (CAT) and ascorbate peroxidase (APX). CONCLUSION:
      Lower level of host genome methylation in 'Ca. P. asteris'-infected periwinkles
      on medium supplemented with BA was significantly elevated after IBA treatment,
      while IBA treatment had no effect on cytosine methylation in periwinkles infected
      with 'Candidatus Phytoplasma ulmi' strain EY-C. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Hormone-dependent recovery is a distinct phenomenon from natural recovery.
      As opposed to spontaneously recovered plants in which elevated peroxide levels
      and differential expression of peroxide-related enzymes were observed, in hormone
      dependent recovery changes in global host genome, methylation coincide with the
      presence/absence of phytoplasma.

PMID- 20796086
TI  - Tetralogy of fallot patient who underwent a classic Blalock-Taussig shunt in
      1962.

PMID- 20796087
TI  - Left ventricular free wall rupture detected by multidetector computed tomography
      after mitral valve replacement.

PMID- 20796088
TI  - Fibrosarcoma of the left superior pulmonary vein with extension to the left
      atrium.

PMID- 20796089
TI  - Surgical treatment of giant intramural left ventricular fibroma in an adult
      patient with refractory ventricular tachycardia.
AB  - Cardiac fibromas are rare benign tumors predominantly diagnosed in children and
      teenagers. We report a 57-year-old male patient with class II dyspnea and angina.
      During electrocardiographic assessment, recurrent ventricular tachycardia was
      present and magnetic resonance imaging revealed a giant (12.5 * 5 * 4 cm)
      intramural left ventricular tumor compatible with cardiac fibroma. After surgical
      biopsy and histological confirmation, open-heart surgical resection was
      successfully performed. After nine months of follow up, the patient remains
      asymptomatic without evidence of ventricular tachycardia.

PMID- 20796090
TI  - Nitinol wire mesh fracture and traumatic left atrial thrombus in a patient with
      atrial septal defect amplatzer occluder.
AB  - Although wire device frame fracture associated with thrombus formation has been
      reported in some types of atrial septal defect occluders, it has not been
      detected in patients with Amplatzer devices. Here, we describe an unusual case of
      Nitinol wire mesh fracture associated with left atrial endocardial damage and
      thrombus formation in an adult with Amplatzer septal occluder.

PMID- 20796091
TI  - Anatomical tricuspid valve replacement in a patient with corrected transposition
      of the great arteries and situs inversus with 90 degrees  clockwise rotation of
      the heart through right thoracotomy.
AB  - The patient was a 34-year-old man with corrected transposition of the great
      arteries and situs inversus who was admitted with dyspnea. He had undergone
      ventricular septal defect closure and pulmonary valve commissurotomy at the age
      of 15. Preoperative examinations revealed severe tricuspid (systemic
      atrioventricular valve) insufficiency associated with dysfunction of the systemic
      (anatomical right) ventricle. The tricuspid valve orifice was shown to open
      dorsally by computed tomography. Because of 90 degrees  clockwise rotation of the
      heart, surgery was performed through right side thoracotomy. Tricuspid valve
      replacement with preservation of all leaflets and chordae tendineae was performed
      successfully, and the patient had an uneventful recovery after surgery.

PMID- 20796092
TI  - Preoperative exchange transfusion for sickle cell disease patients undergoing
      open-heart surgery: an exception to the rule.
AB  - Preoperative exchange transfusion is a routine practice in patients with sickle
      cell disease having elevated sickle cell hemoglobin levels (>40%) undergoing open
      heart surgery on cardiopulmonary bypass. A new approach toward acceptance and
      management of sickle cell disease patients with high sickle cell hemoglobin
      levels for open-heart surgery without preoperative exchange transfusion of blood
      is presented.

PMID- 20796093
TI  - Myasthenia gravis--an unexpected cause of respiratory failure and reversible left
      ventricular dysfunction after cardiac surgery.
AB  - We report a case of postpericardiotomy myasthenia gravis. A 68-year-old male
      patient without prior history of neuromuscular or autoimmune disorders presented
      with respiratory failure and severe left ventricular dysfunction four weeks after
      mitral valve replacement. Markedly elevated acetylcholine receptor antibodies
      were noted, and the patient responded promptly to immunologic therapy. Awareness
      of this rare but potentially fatal consequence of cardiac surgery may allow the
      early institution of specific treatment.

PMID- 20796094
TI  - Evolving fairness in research on human subjects.

PMID- 20796095
TI  - Healing patterns revealed in middle school boys' experiences of being bullied
      using Roger's Science of Unitary Human Beings (SUHB).
AB  - PROBLEM: Although two of the primary risk factors for being bullied include
      "male" and "middle school" status, a gap in knowledge exists of middle school
      boys' personal accounts and meanings of being bullied and their healing. METHODS:
      Giorgi's descriptive phenomenological approach using open-ended semi-structured
      individual interviews was used to collect and analyze evidence related to middle
      school boys' lived experiences of being bullied and healing. Roger's Science of
      Unitary Human Beings (SUHB) guided interpretation of the healing patterns.
      FINDINGS: Three patterns of healing were identified in boys' experiences: meaning
      making, self-transcendence, and nonviolently claiming personal power.
      CONCLUSIONS: Evidence of healing patterns exists in middle school boys'
      experiences of being bullied, offering a foundation for further research and
      practice focused on healing. When working with middle school boys who have been
      bullied, nurses need to ask about their experiences and promote their healing.

PMID- 20796096
TI  - The role of electronic communication technology in adolescent dating violence.
AB  - PROBLEM: Adolescent dating violence and electronic aggression are significant
      public health problems. The purpose of this study was to (a) identify ways in
      which technology is used in dating violence and (b) present examples of dating
      violence in which electronic aggression played a salient role. METHODS: The data
      set included the transcribed narratives of 56 young adults who had described
      their adolescent dating violence experiences for an on going study. FINDINGS:
      Eight ways in which technology is used in dating violence were identified using
      qualitative descriptive methods. CONCLUSIONS: The findings indicate that
      electronic communication technology influences dating violence by redefining
      boundaries between dating partners.

PMID- 20796097
TI  - The concept of patient satisfaction in adolescent psychiatric care: a qualitative
      study.
AB  - PROBLEM: Few studies have asked how adolescents perceive the quality of
      psychiatric care. Therefore, the aim of the study was to explore adolescents'
      perception of quality of care and of satisfying treatment outcomes. METHODS:
      Fourteen adolescents participated in this hermeneutic study. FINDINGS: Several
      concepts describing adolescents' perspective of quality of care were found:
      secure place, tough love, peer solidarity, self-expression, and person not
      patient. Concepts describing satisfying treatment outcomes fell into four
      categories: improved mental health, personal development, strengthening of the
      self, and improved family relations. CONCLUSIONS: By casting light on users'
      perspectives, the study offers guidance for improvement of quality of care and
      for the development of patient satisfaction instruments.

PMID- 20796098
TI  - Pediatric psychotropic medication initiation and adherence: a literature review
      based on social exchange theory.
AB  - TOPIC: Psychotropic medication initiation and adherence is an identified problem.
      This literature review explores factors that determine families' decisions to
      initiate, sustain, or discontinue use of psychotropic medication in children and
      adolescents. Social exchange theory is used as a framework to explore decisions
      to initiate and adhere to psychotropic medications. PURPOSE: Contributing factors
      related to psychotropic medication initiation, adherence, and discontinuation are
      explored. Themes in the literature encompassing costs and benefits of
      psychotropic medication adherence include family experiences with adverse
      effects, previous psychotropic medication experience, medication psychoeducation,
      stigma, societal views about psychotropic medication, particular diagnosis, the
      effect of comorbid diagnosis on adherence, attitudes and beliefs about medication
      by both children and parents, and relationships with the provider. The impact of
      family demographics including parent gender, age of the child, ethnicity, and
      parent educational level on psychotropic medication adherence is evaluated.
      SOURCES: International and U.S. studies from Medline, Cumulative Index for
      Nursing and Allied Health Literature and PsychInfo evaluating medication
      initiation and adherence in the pediatric psychiatric population and social
      exchange theory was incorporated from relevant textbook resources. CONCLUSIONS:
      Rewards experienced from medication treatment include improvement in symptoms,
      school performance and family relationships, and reduced level of parenting
      stress. Identified costs include impact of adverse side effects, social stigma,
      lack of response, fears of addiction, and changing the child's personality.
      Acceptance of the diagnosis influences adherence while medication education has
      varying effects. Families' attitudes, beliefs and perceptions about psychiatric
      illness and treatment play a large role in medication treatment decisions. A
      trusting provider relationship has a positive effect on adherence. Psychosocial
      treatment alternatives are preferred. With maturation, adolescents have more
      influence on decisions related to adherence.

PMID- 20796099
TI  - The mediating effects of stress and coping on depression among adolescents in
      China.
AB  - AIMS: To explore gender differences in Chinese adolescent depression related to
      the mediating effects of stress and coping. METHODS: The data were collected
      using a cross-sectional design from a multisite follow-up investigation of
      adolescent physical and psychological study carried out in China. The study
      population consisted of 17,622 students aged from 11 to 22 years of age in junior
      high, senior high schools, and colleges/universities from eight large cities in
      China. RESULTS: Overall, 44.3% of the sample reported depression during the past
      week. Male adolescents were more likely to have depression than female
      counterparts (46.8% versus 41.7%), especially those aged <15 and >17 years of
      age. Overall, stress in boys was statistically higher than that of girls. Boys
      experienced high levels of stress from school, family, health, and romantic
      domains, while girls suffered a higher level of peer stress. A multivariate
      logistic regression model showed that a high level of total stress was
      significantly associated with increased risk for depression, while peer stress
      and positive coping style were protective factors for depression in both boys and
      girls in China. CONCLUSIONS: Unlike their Western counterparts, Chinese boys
      suffered more depression than girls, which is partly due to more stressful life
      events and less positive coping style. Our study has important implications for
      health officers and public health professionals to pay much attention to the
      relationship between stress and coping style in prevention on adolescent
      depression.

PMID- 20796100
TI  - Psychometric testing of the children's resourcefulness scale.
AB  - PROBLEM: Resourcefulness is known to reduce depression in adults, but its effects
      on children are less well known, possibly for lack of a psychometrically sound
      measure. METHODS: This study examined the reliability and validity of the 32-item
      Children's Self-Control Scale (C-SCS), which measures resourcefulness, in 122
      school-aged children. FINDINGS: Standard scale refinement methods produced a 10
      item scale with alpha= .72 and correlations with the C-SCS (r = .86), positive
      thoughts (r = .38), and depressive symptoms (r =-.32). Factor analysis revealed
      two factors: problem-solving and delay of gratification. CONCLUSIONS: The 10-item
      scale may be useful for identifying children who are not resourceful and are at
      risk for depression.

PMID- 20796101
TI  - Siblings and family environments of persons with autism spectrum disorder: a
      review of the literature.
AB  - OBJECTIVES: The purpose of this literature review is to summarize studies on
      siblings of individuals with autism spectrum disorders (ASD) in four major areas,
      to identify gaps in the literature, and to propose future directions for research
      of siblings of persons with ASD. DESIGN AND METHODS: A systematic review of
      research published within the past 10 years in peer review journals includes
      investigations on siblings' and parental characteristics, as well as sibling
      behaviors, relationships, and adaptation. Twelve studies are synthesized to
      include purpose, findings, and discussion relating it to previous work. RESULTS:
      Siblings are influenced by the context of their families that are impacted by
      biological, psychological, sociological, and ecological factors. Research studies
      are primarily exploratory and no intervention studies are identified. CONCLUSION:
      The literature review of parental and sibling characteristics, relationships, and
      adaptation support intervention measures for siblings and family members of
      persons with autism. Assessment of siblings is necessary to identify those who
      may be at risk for future adjustment problems and maladaptive behaviors.

PMID- 20796102
TI  - The social determinants of health and mental health: global foundations for
      improving child and family mental health.

PMID- 20796103
TI  - Educating the workforce who cares for the pediatric population.

PMID- 20796106
TI  - Platelet-rich plasma may prevent titanium-mesh exposure in alveolar ridge
      augmentation with anorganic bovine bone.
AB  - OBJECTIVE: Bone augmentation with the titanium-mesh (Ti-mesh) technique is
      susceptible to a large rate of complications such as morbidity of bone graft
      donor site, and mesh exposure to the oral cavity. The purpose of this study was
      to evaluate the effectiveness of anorganic bovine bone (ABB) in alveolar bone
      augmentation with the Ti-mesh technique. In addition, we investigated the effect
      of platelet-rich plasma (PRP) in preventing mesh exposure by using it to cover
      the Ti-mesh. PATIENTS AND METHODS: Patients included in the clinical trial were
      randomly allocated by a blinded assistant into two groups. The 30 patients
      recruited for this study underwent 43 alveolar bone augmentation with the Ti-mesh
      technique using ABB as graft material in all of them. In 15 patients, the Ti
      meshes were covered with PRP (PRP group) whereas in the other 15 the Ti-meshes
      were not (control group). After 6 months, patients were called for clinical,
      radiographic, and histological evaluation, and implant placement surgery. A total
      of 97 implants were placed in the augmented bone and their evolution was followed
      up for a period of 24 months. RESULTS: Significant differences were found between
      the two study groups in terms of complications and bone formation. In the control
      group, 28.5% of the cases suffered from mesh exposure, while in the PRP group, no
      exposures were registered. Radiographic analysis revealed that bone augmentation
      was higher in the PRP group than in the control group. Overall, 97.3% of implants
      placed in the control group and 100% of those placed in the PRP group were
      successful during the monitoring period. We suggest that the positive effect of
      PRP on the Ti-mesh technique is due to its capacity to improve soft tissue
      healing, thereby protecting the mesh and graft material secured beneath the
      gingival tissues. CONCLUSIONS: Alveolar bone augmentation using ABB alone in the
      Ti-mesh technique is sufficient for implant rehabilitation. Besides, covering the
      Ti-meshes with PRP was a determining factor in avoiding mesh exposure. Ti-mesh
      exposure provoked significant bone loss, but in most cases it did not affect the
      subsequent placement of implants.

PMID- 20796107
TI  - Blood pressure and left ventricular mass in subjects with type 2 diabetes and
      gingivitis or chronic periodontitis.
AB  - INTRODUCTION: This study aimed to answer the question of whether chronic
      periodontitis in subjects with type 2 diabetes mellitus is associated with
      increased left ventricular mass (LVM) and systemic and central blood pressure
      (CBP). MATERIAL AND METHODS: One hundred and fifty-five subjects with type 2
      diabetes (67 F, 88 M, mean age 61.1+/-6.9 years, BMI 32.7+/-5.7 kg/m(2)) were
      divided according to their periodontal status into biofilm-gingival interface -
      healthy (BGI-H, 14 subjects), BGI-gingivitis (BGI-G, 119 subjects) and BGI
      periodontitis (BGI-P, 22 subjects) groups. In all subjects, LVM, systemic and CBP
      were measured. The LVM index (LVMI) was calculated. RESULTS: (1) BGI-P and BGI-G
      subjects, respectively, had higher (mean; 95% CI) LVM (238.6 g; 206.6-267.4 and
      222.8 g; 207.0-238.2) versus BGI-H subjects (170.3 g; 125.5-217.8).?(2) BGI-P and
      BGI-G subjects, respectively, had higher (mean; 95% CI) LVM1 (95.2 g/m(2) ; 82.9
      107.4) and 87.8 g/m(2) ; 81.5-94.1) versus BGI-H subjects (63.7 g/m(2) ; 45.2
      62.3).?(3) BGI-P subjects had higher central and systemic systolic and diastolic
      blood pressure than subjects from BGI-G and BGI-H groups. CONCLUSION: In subjects
      with type 2 diabetes, periodontitis and gingivitis are associated with increased
      LVM and periodontitis is associated with increased central and systemic blood
      pressure.

PMID- 20796108
TI  - Flapless immediate implant placement with or without immediate loading: a
      histomorphometric study in beagle dog.
AB  - OBJECTIVE: To assess the osseointegration process after flapless immediate
      implant placement with or without immediate loading. MATERIAL AND METHODS: This
      study was carried out on six beagle dogs. Four implants were placed in the lower
      jaw (two per side) in each dog immediately after tooth extraction (3rd and 4th
      premolars). Flapless immediate implant placement was performed in one
      hemimandible (control). The same procedure was carried out in the contra-lateral
      side and immediate prosthesis was connected with occlusal contacts (test). After
      3 months of healing, the dogs were sacrificed for histomorphometric analysis.
      RESULTS: Twelve implants were placed in each group. None of the implants and
      prosthesis was lost. The percentage of bone-to-implant contact (BIC %) was
      similar in both groups: 82.72% (test) and 76.96% (control). Differences were
      found neither in the inter-thread bone area (test: 83.45%, control: 80.65%) nor
      in peri-implant bone area (test: 94.37%, control: 94.81%). CONCLUSION: In this
      animal model where the implants were well within the confines of the extraction
      socket, osseointegration following flapless immediate implant placement and
      loading can be achieved in the same manner as immediate placement without
      loading.

PMID- 20796132
TI  - Description of Paratetrahymena parawassi n. sp. using morphological and molecular
      evidence and a phylogenetic analysis of Paratetrahymena and other taxonomically
      ambiguous genera in the order Loxocephalida (Ciliophora, Oligohymenophorea).
AB  - The marine scuticociliate Paratetrahymena parawassi n. sp. is described on the
      basis of morphology, especially infraciliature, and the sequence of its small
      subunit (SSU) rRNA gene to become the second known member of its genus.
      Paratetrahymena and other ciliates in the order Loxocephalida possess a mixture
      of morphological and morphogenetic features characteristic of the subclasses
      Hymenostomatia and Scuticociliatia. Accordingly, we used SSU rRNA sequences to
      analyze the phylogeny of Paratetrahymena and three other loxocephalid genera.
      Paratetrahymena and Cardiostomatella vermiformis formed a moderately well
      supported clade that diverged at a deep level from all other scuticociliates,
      supporting separation of loxocephalids from other scuticociliates as a
      suprafamilial taxon. Sathrophilus holtae was a sister taxon to Paratetrahymena
      and Cardiostomatella in a poorly supported, unresolved relationship;
      nevertheless, association of all three genera into a single clade was supported
      by an approximately unbiased (AU) test. Any association of these genera singly or
      as a group with the Hymenostomatia was rejected decisively by AU tests and by a
      complete absence in the loxocephalids of the unique nucleotide identities that
      distinguish hymenostomes. Therefore, the morphological and morphogenetic
      similarities of loxocephalids to hymenostomes may be plesiomorphies, and the
      conflicting mix of scuticociliate and hymenostome characteristics seen in
      loxocephalids may result from differing rates of character evolution.
      Dexiotrichides pangi and Urocentrum, which is currently classified as a
      peniculid, formed a small clade that associated with hymenostomes and peritrichs.
      Monophyly of the Loxocephalida with Dexiotrichides and/or Urocentrum included was
      not rejected by AU; however, inclusion of Urocentrum in the Peniculia was
      rejected by AU tests. A hypothesis is offered to explain the lack of resolution
      of loxocephalid ciliates and Urocentrum in phylogenetic trees, namely that their
      phylogenetic positions are influenced by a combination of heterogeneous data and
      long-branch attraction caused by poor representation of taxa in analyses. The
      well-known genus Cyclidium, a member of the order Pleuronematida, was revealed to
      be polyphyletic as a byproduct of our analyses of loxocephalids. In particular,
      Cyclidium porcatum appears to fall outside the clade containing typical members
      of the subclass Scuticociliatia and thus invites investigation as a possible
      member of the order Loxocephalida.

PMID- 20796133
TI  - Comparing three different methods to detect selective loci using dominant
      markers.
AB  - We carried out a simulation study to compare the efficiency of three alternative
      programs (DFDIST, DETSELD and BAYESCAN) to detect loci under directional
      selection from genome-wide scans using dominant markers. We also evaluated the
      efficiency of correcting for multiple testing those methods that use a classical
      probability approach. Under a wide range of scenarios, we conclude that BAYESCAN
      appears to be more efficient than the other methods, detecting a usually high
      percentage of true selective loci as well as less than 1% of outliers (false
      positives) under a fully neutral model. In addition, the percentage of outliers
      detected by this software is always correlated with the true percentage of
      selective loci in the genome. Our results show, nevertheless, that false
      positives are common even with a combination of methods and multitest correction,
      suggesting that conclusions obtained from this approach should be taken with
      extreme caution.

PMID- 20796134
TI  - Testing hybridization hypotheses and evaluating the evolutionary potential of
      hybrids in mangrove plant species.
AB  - Natural hybridization is of marked importance from global to local biological
      diversity. In mangroves, species ranges overlap extensively with one another and
      species share a long overlap of flowering time. Although hybridization has been
      suggested, patterns of hybridization and the evolutionary potential of hybrids
      are not yet fully understood. This study provides molecular evidence for the
      parental origins and status of hybrids in the dominant mangrove genus Rhizophora
      based on comparisons of chloroplast and nuclear phylogenies and estimations of
      genetic relatedness and structure from inter-simple sequence repeat (ISSR)
      markers. Phylogenetic analyses indicate that almost all species can act as
      maternal parents to hybrids and that hybridization can be bidirectional. Bayesian
      analyses indicate that hybrids are simple F(1) s, and no trace of backcrossing
      was detected within populations. Hybridization, for the most part, occurs almost
      only locally and dispersal of hybrid individuals is limited beyond the hybrid
      sites.

PMID- 20796135
TI  - Alternative parasite development in transmission strategies: how time flies!
AB  - Among parasitic platyhelminths with complex life cycles, it has been well
      documented that transmission opportunities are the main forces shaping the
      diversity of life-history traits and parasite developmental strategies. While
      deviations in the development pathway usually involve shortening of life cycles,
      their extension may also occur following perception of remaining time by
      parasites. Polystoma gallieni, the monogenean parasite of Hyla meridionalis, is
      able to trigger two alternative developmental strategies depending on the
      physiological stage of the tadpoles upon which larvae attach. The distribution
      and reproductive outputs of both resulting phenotypes were surveyed to address
      questions about the dynamics of transmission in natural environments. Because
      modifications in the completion of life cycles can have drawbacks which may
      perturb the dynamic equilibrium of the resulting host-parasite systems,
      experimental infestations were also performed to assess parasite-parasite
      interactions. Our results suggest that the bladder adult phenotype, which
      involves transmission between frogs and tadpoles, is supplied secondarily by the
      branchial phenotype which involves transmission between tadpoles and metamorphs.
      They also support the occurrence of finely tuned trade-offs between hosts and
      parasites and highlight positive trends behind the extension of direct life
      cycles, in which host-derived signals account for the remaining time to achieve
      parasitic transmission.

PMID- 20796136
TI  - Genetic variation in herbivore resistance and tolerance: the role of plant life
      history stage and type of damage.
AB  - Information of the patterns of genetic variation in plant resistance and
      tolerance against herbivores and genetic trade-offs between these two defence
      strategies is central for our understanding of the evolution of plant defence. We
      found genetic variation in resistance to two specialist herbivores and in
      tolerance to artificial damage but not to a specialist leaf herbivore in a long
      lived perennial herb. Seedlings tended to have genetic variation in tolerance to
      artificial damage. Genetic variation in tolerance of adult plants to artificial
      damage was not consistent in time. Our results suggest that the level of genetic
      variation in tolerance and resistance depends on plant life-history stage, type
      of damage and timing of estimating the tolerance relative to the occurrence of
      the damage, which might reflect the pattern of selection imposed by herbivory.
      Furthermore, we found no trade-offs between resistance and tolerance, which
      suggests that the two defence strategies can evolve independently.

PMID- 20796137
TI  - Co-variation between the intensity of behavioural manipulation and parasite
      development time in an acanthocephalan-amphipod system.
AB  - Pomphorhynchus laevis, a fish acanthocephalan parasite, manipulates the behaviour
      of its gammarid intermediate host to increase its trophic transmission to the
      definitive host. However, the intensity of behavioural manipulation is variable
      between individual gammarids and between parasite populations. To elucidate
      causes of this variability, we compared the level of phototaxis alteration
      induced by different parasite sibships from one population, using experimental
      infections of Gammarus pulex by P. laevis. We used a naive gammarid population,
      and we carried out our experiments in two steps, during spring and winter.
      Moreover, we also investigated co-variation between phototaxis (at different
      stages of infection, 'young' and 'old cystacanth stage') and two other fitness
      related traits, infectivity and development time. Three main parameters could
      explain the parasite intra-population variation in behavioural manipulation. The
      genetic variation, suggested by the differences between parasite families, was
      lower than the variation owing to an (unidentified) environmental factor.
      Moreover, a correlation was found between development rate and the intensity of
      behavioural change, the fastest growing parasites being unable to induce rapid
      phototaxis reversal. This suggests that parasites cannot optimize at the same
      time these two important parameters of their fitness, and this could explain a
      part of the variation observed in the wild.

PMID- 20796138
TI  - Myocardial ischemia, pancreatitis and ERCP.

PMID- 20796139
TI  - Electromagnetic thermoablation to treat thrombocytopenia in cirrhotic and
      hypersplenic rats.

PMID- 20796140
TI  - Non-invasive assessment of liver fibrosis: time to move from cross-sectional
      studies to longitudinal ones.

PMID- 20796141
TI  - Peginterferon for chronic hepatitis B: predicting success with on-treatment
      benchmarks.

PMID- 20796143
TI  - New endoscopic and surgical treatment options for early esophageal
      adenocarcinoma.
AB  - Although the outcome for advanced stage esophageal cancer is poor, the early
      detection and treatment of early stage disease is usually associated with a much
      better outcome. Until recently, esophagectomy has been the treatment of choice in
      fit patients. However, morbidity is significant, and this has encouraged the
      development of newer endoscopic treatments that preserve the esophagus. These
      techniques include ablation and mucosal resection. Promising results are
      described, and endoscopic methods might provide a reasonable alternative for the
      treatment of early esophageal cancer. However, follow-up remains short and
      endoscopic treatment does not deal with potential lymphatic spread. Hence,
      careful selection is required. Minimally invasive techniques for esophageal
      resection have also been shown to be feasible, although there is only limited
      evidence that they reduce postoperative morbidity. Better data are still required
      to demonstrate improved outcomes from endoscopic treatment and minimally invasive
      esophagectomy.

PMID- 20796144
TI  - Pathology of combined hepatocellular-cholangiocarcinoma.
AB  - Combined hepatocellular-cholangiocarcinoma is a rare primary neoplasm in the
      liver. It has gained increasing recognition recently, which in part may be due to
      more extensive sampling of the explants and surgical resection specimens, the
      diagnostic challenges encountered in the clinical practice, and the yet to be
      determined clinical outcome, but partly may be attributed to its intriguing
      histogenesis/cells of origin. This review aims to update combined hepatocellular
      cholangiocarcinoma with an emphasis on the pathological diagnosis, including the
      differential diagnosis and its diagnostic pitfalls, the possible cell of origin
      of this neoplasm, and its clinical outcome.

PMID- 20796145
TI  - Reversal of the tolerance phenomenon by the intermittent administration of a
      histamine H2-receptor antagonist.
AB  - BACKGROUND AND AIM: The attenuated antisecretory activity of H2-receptor
      antagonists (H2RA) during continuous administration is referred to as the
      tolerance phenomenon. A previous study indicated that Helicobacter pylori (H.
      pylori) infection prevents the occurrence of tolerance to H2RA. In the present
      study, we investigated whether intermittent (every other day) administration
      prevents the tolerance phenomenon in H. pylori-negative patients. METHODS: Ten H.
      pylori-negative, healthy volunteers were included in the study. All of the
      patients underwent two courses of H2RA (lafutidine) administration: 21-day
      continuous administration (every day), followed by 21-day intermittent
      administration (every other day), with at least a 21-day lafutidine-free period
      between the first and second courses. All of the patients were examined by
      ambulatory intragastric pH monitoring five times: before medication, and on days
      1 and 21 of the first (continuous) and second (intermittent) courses of
      lafutidine (10 mg b.d.) in a crossover fashion. RESULTS: The continuous
      administration of lafutidine had a significantly attenuated, acid-suppressing
      effect in H. pylori-negative patients, and showed evidence of the tolerance
      phenomenon. However, the tolerance phenomenon was not observed through
      intermittent administration. CONCLUSIONS: These results demonstrated that in H.
      pylori-negative patients, tolerance to H2RA, induced by continuous lafutidine
      administration, was reversed by subsequent intermittent administration.

PMID- 20796146
TI  - Quantitative serum HBsAg and HBeAg are strong predictors of sustained HBeAg
      seroconversion to pegylated interferon alfa-2b in HBeAg-positive patients.
AB  - BACKGROUND AND AIM: To evaluate the usefulness of quantitative hepatitis B
      surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) for predicting HBeAg
      seroconversion in chronic hepatitis B patients treated with conventional
      interferon (IFN) alfa-2b or PegIFN alfa-2b. METHODS: Fifty-eight patients were
      enrolled; 29 for the training group and 29 for the validating group.
      Quantification of HBsAg and HBeAg was carried out at baseline, week 12, week 24,
      and then again at 12 and 24 weeks follow up, respectively, for two groups.
      Sixteen patients in the training group were followed up for 5 years. RESULTS: The
      cutoff of 1500 IU/mL in serum HBsAg at week 12 had a positive predictive value
      (PPV) of 33% and a negative predictive value (NPV) of 91%, and 2890 IU/mL at week
      24 had a PPV of 43% and an NPV of 95% for HBeAg seroconversion at week 48. The
      cutoff of 17.55 Paul Ehrlich Institute units/mL (PEI-U/mL) in serum HBeAg at week
      12 had a PPV of 38% and an NPV of 95%, and 8.52 PEI-U/mL at week 24 had a PPV of
      44% and a NPV of 100% for HBeAg seroconversion at week 48. Moreover the HBsAg and
      HBeAg levels of PegIFN alfa-2b group were lower than those of the conventional
      IFN alfa-2b group. During follow up, patients with HBeAg seroconversion remained
      HBeAg negative and none of them progressed to cirrhosis, but among the patients
      with non-HBeAg seroconversion, two progressed to cirrhosis. Two additional
      patients with negative HBeAg were observed. CONCLUSIONS: On-treatment serum HBsAg
      and HBeAg had high predictive values to predict sustained HBeAg seroconversion by
      PegIFN alfa-2b. Patients who cleared HBeAg had better survival free of hepatic
      complications during long-term follow-up study.

PMID- 20796147
TI  - Is endoscopic forceps biopsy enough for a definitive diagnosis of gastric
      epithelial neoplasia?
AB  - BACKGROUND AND AIM: Endoscopic forceps biopsy (EFB) as the primary histological
      diagnosis of gastric epithelial neoplasia (GEN) is debated in the era of
      endoscopic resection (ER). Our aim was to investigate the diagnostic reliability
      of EFB in patients with GEN compared with ER specimens as the reference standard
      for the final diagnosis in a large consecutive series. METHODS: This was a cross
      sectional retrospective study at a tertiary-referral center. A total of 354
      consecutive patients with 397 GENs underwent ER (endoscopic mucosal resection or
      endoscopic submucosal dissection). Discrepancy rates between the histological
      results from EFB and ER specimens were assessed. Discrepancies that could affect
      patient outcome or clinical care were considered major. RESULTS: The overall
      histological discrepancy rate between EFB and ER specimens was 44.5% (95%
      confidence interval [CI], 39.7-49.5%) among the enrolled patients. The overall
      discrepancy rate was significantly higher in the intraepithelial neoplasia (IEN)
      group than in the carcinoma group (49.8% vs 25.6%, P < 0.001). The major
      discrepancy rate was also significantly higher in the IEN group than in the
      carcinoma group (36.6% vs 7.0%, P < 0.001). In subgroup analysis of the IEN
      group, a major histological discrepancy rate of 33.6% (70/208) for low-grade and
      42.7% (44/103) for high-grade IEN was found, respectively. CONCLUSIONS:
      Endoscopic forceps biopsy was insufficient for a definitive diagnosis and
      therapeutic planning in patients with GEN. ER should be considered as not only
      definitive treatment but also a procedure for a precise histological diagnosis
      for lesions initially assessed as GEN by forceps biopsy specimens.

PMID- 20796148
TI  - Fine-tuning the criteria for strip biopsy and endoscopic submucosal dissection
      improves the outcome of early gastric carcinoma treatment.
AB  - BACKGROUND AND AIM: Strip biopsy and endoscopic submucosal dissection (ESD) have
      been developed as a local treatment for early gastric cancer (EGC). However, the
      lesion criteria for the use of ESD, rather than strip biopsy, remain to be
      elucidated. METHODS: On the basis of reviews of literature and our observations
      concerning the outcome of strip biopsy, we set the criteria for selecting strip
      biopsy and ESD as follows. The indications for strip biopsy were lesions less
      than 10 mm in size and located in the anterior wall or greater curvature of the
      lower and middle stomach. ESD was indicated for all other lesions. The validity
      of the criteria was then analyzed prospectively in 156 patients. The rate of en
      bloc R0 resection and local recurrence were evaluated. RESULTS: Subsequently, 156
      lesions were divided according to the criteria and were endoscopically resected
      by strip biopsy (n = 13) or ESD (n = 143). The en bloc R0 resection rates for the
      whole group and the strip biopsy and ESD groups was 93.5% (146/156), 92.3%
      (12/13), and 93.7% (134/143), respectively. None of the patients had suffered
      from local recurrence in either the strip biopsy or ESD groups. CONCLUSION: The
      validity of our criteria for selecting strip biopsy and ESD was verified. Our
      criteria exploit the advantages of both procedures and obtain better endoscopic
      therapy outcomes for EGC.

PMID- 20796149
TI  - Myocardial ischemia during endoscopic retrograde cholangiopancreatography: an
      overlooked issue with significant clinical impact.
AB  - BACKGROUND AND AIM: The occurrence of peri-procedural myocardial ischemia with
      endoscopic retrograde cholangiopancreatography (ERCP) has been documented, but
      its significance remains controversial. This study aimed to investigate the
      incidence and risk factors of myocardial ischemia during ERCP procedures and to
      analyze the potential association between myocardial ischemia and post-ERCP
      complications. METHODS: Ambulatory 24-h ST-segment monitoring from 30 min prior
      to 24 h after ERCP was obtained on 71 patients from September 2006 to August
      2007. Changes in vital signs during ERCP, post-ERCP complications, and their
      outcomes were recorded and analyzed. RESULTS: Cardiac ischemia occurred in 13
      patients (18.3%) during ERCP and one patient developed myocardial infarction.
      More patients in the ischemic group (38.5%) than in the non-ischemic group (5.2%)
      had ST-T changes in pre-ERCP resting electrocardiography (P < 0.01). Hypotension
      during ERCP was found only in the ischemic group (15.4% vs 0%; P = 0.03).
      Patients with cardiac ischemia during ERCP had a significantly higher rate of
      elevated serum amylase and lipase levels (53.8% vs 15.5%; P < 0.01) and post-ERCP
      pancreatitis (30.8% vs 6.9%; P = 0.03). Multivariable logistic regression
      analysis revealed that cardiac ischemia during ERCP (OR: 5.21, P = 0.050) and
      pancreatic duct cannulation (OR: 5.7, P = 0.036) were independent predictors for
      post-ERCP pancreatitis. CONCLUSIONS: ST-T changes on resting electrocardiography
      and intra-procedural hypotension are risk factors of myocardial ischemia during
      ERCP. Post-ERCP hyperamylasemia, hyperlipasemia, and pancreatitis were associated
      with myocardial ischemia during ERCP.

PMID- 20796150
TI  - Prospective evaluation of a clinical guideline recommending early patients
      discharge in bleeding peptic ulcer.
AB  - BACKGROUND AND AIM: To validate an early discharge policy in patients admitted
      with upper gastrointestinal bleeding (UGIB) due to ulcers. METHODS: Patients with
      gastroduodenal ulcer or erosive gastritis/duodenitis were included in a previous
      study aiming to develop a practice guideline for early discharge of patients with
      UGIB. Variables associated with unfavorable evolution were analyzed in order to
      identify patients with low-risk of re-bleeding. After that, a one-year
      prospective analysis of all UGIB episodes was carried out. RESULTS: A total of
      341 patients were identified in the retrospective study. Variables associated
      with unfavorable evolution were: systolic blood pressure < or = 100 mmHg, heart
      rate > or = 100 bpm, and a Forrest endoscopic classification of severe. 10% of
      patients were immediately discharged; however, if predictive variables obtained
      in the multivariate analysis had been used, hospitalization could have been
      prevented in 34% of patients. A total of 77 patients were included in the
      prospective analysis. Although only 19.5% of patients were immediately discharged
      without complications, 29 patients (37.7%) were theoretically suitable for early
      discharge. CONCLUSIONS: Patients with UGIB who have clean-based ulcers and are
      stable on admission can be safely discharged immediately after endoscopy.
      Implementation of the clinical practice guideline safely reduced hospital
      admission for those patients.

PMID- 20796151
TI  - Perforated peptic ulcer in southeastern Taiwan.
AB  - BACKGROUND: No studies focus on the population with perforated peptic ulcer in
      southeastern Taiwan. The present study aimed to assess the differences between
      the different races and the risk factors related to mortality and morbidity in
      postoperative patients in southeastern Taiwan. METHODS: The medical records of
      237 patients were reviewed retrospectively. The following factors were analyzed:
      patient profiles, coexisting illnesses, diagnostic method, fever, preoperative
      shock, clinical data at emergency room, delay operation, site of perforation,
      operative method, positive ascites culture, species of microbes in ascites
      culture, postoperative complications, death and the length of hospital stay.
      RESULTS: Aborigines were significantly different from non-aborigines in the ratio
      of female cases and in the habits of alcohol drinking and betel nut chewing.
      There were also four significantly different variables between them: fever,
      hemoglobin value, site of perforation and operative method. Total postoperative
      complication rate was 41.3% and 39 patients (16.6%) died. In multivariate
      analysis, age > or = 65 years, lipase > upper normal limit and preoperative shock
      were independent predictors of mortality. Significant risk factors associated
      with morbidity were NSAIDs use, creatinine > 1.5 mg/dL and preoperative shock.
      CONCLUSION: Aborigines were different from non-aborigines in several categories.
      In southeastern Taiwan, NSAIDs use, creatinine > 1.5 mg/dL and preoperative shock
      were independent risk factors of morbidity, and age > or = 65 years, lipase >
      upper normal limit and preoperative shock were independent risk factors of
      mortality in postoperative perforated peptic ulcer. Lipase > upper normal limit
      is needed for further research on the influence on mortality.

PMID- 20796152
TI  - Clinicopathologic features and clinical outcomes of gastric cancer that initially
      presents with disseminated intravascular coagulation: a retrospective study.
AB  - BACKGROUND AND AIM: Few systematic studies have been published on prognosis and
      clinical outcome of gastric cancer patients with disseminated intravascular
      coagulation (DIC) as the first presentation of malignancy. We evaluated the
      clinicopathologic features and clinical outcomes of this population. METHODS: We
      reviewed the medical records of patients with metastatic or recurred gastric
      cancer that initially presented with DIC. RESULTS: Twenty-one patients were
      included. Median age was 47 years (range, 24-72 years). Eighteen patients (85.7%)
      had bone metastasis, and nine patients (42.9%) had hemorrhagic complication of
      DIC. Fourteen patients received palliative chemotherapy, and seven patients
      received best supportive care (BSC). The most common factor influencing the
      decision to abandon the palliative chemotherapy was uncontrolled bleeding
      (57.1%). The median overall survival (OS) of all patients was 58 days (range, 2
      342 days). The OS was significantly shorter in BSC than in the chemotherapy group
      (median, 16 vs 99 days, P < 0.001). In multivariate analysis, chemotherapy was
      independently associated with longer OS. In the chemotherapy group, the response
      to treatment was evaluable in 11 patients: two (18.2%) had a partial response,
      five (45.5%) had stable disease and four (36.4%) had progressive disease. The OS
      of patients with progressive disease was significantly longer in the chemotherapy
      group than in the BSC group (median, 92 vs 16 days, P = 0.009). CONCLUSIONS: The
      prognosis is poor with gastric cancer that initially presents with DIC but
      palliative chemotherapy, compared with BSC, prolongs OS. Therefore, early and
      intensive management for correctable DIC followed by chemotherapy should be
      considered in this population.

PMID- 20796153
TI  - Low alpha-fetoprotein hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: A large proportion of hepatocellular carcinoma (HCC) patients
      do not secrete elevated levels of the tumor marker alpha-fetoprotein (AFP). There
      is little published guide to prognostic features of this patient subset. METHODS:
      We interrogated a large HCC database in which all patients had been followed
      until death, to examine which features might be prognostically useful. RESULTS:
      We found 413 biopsy-proven unresectable HCC patients with low serum AFP values.
      Serum gamma glutamyl transpeptidase (GGTP) levels were one of the most
      significant factors for survival. This dichotomization into low and high GGTP
      levels separated the patients into distinctive survival ranges. Patients with
      GGTP levels < 110 U/100 mL and small tumors had longest survival > 795 days.
      Patients with GGTP > or = 110 U/mL and large tumors with the presence of portal
      vein thrombosis had the shortest survival range of 300-560 days. CONCLUSIONS:
      Serum levels of the onco-fetal protein GGTP represent a useful prognostic
      parameter in HCC patients with low AFP levels.

PMID- 20796154
TI  - Effects of branched-chain amino acid-enriched nutrient for patients with
      hepatocellular carcinoma following radiofrequency ablation: a one-year
      prospective trial.
AB  - BACKGROUND AND AIM: This prospective control study examined whether
      supplementation with branched-chain amino acid (BCAA)-enriched nutrients can help
      maintain and improve residual liver function and nutritional status in cirrhotic
      patients with hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA).
      METHODS: Subjects were 49 patients with hepatitis C-related HCC who underwent
      RFA. Two groups were formed: BCAA group (BCAA-enriched nutrient, aminoleban EN)
      and controls (standard diet only). Event-free survival rate, liver function
      tests, and Short Form (SF)-8 scores were evaluated in both groups before and one
      year after RFA. Energy metabolism using indirect calorimetry was measured before
      and after 3 months. RESULTS: Complete data were obtained from 35 patients (BCAA
      group, n = 20; controls, n = 15). Six events (death, recurrence of HCC, rupture
      of esophageal varices and liver failure) occurred during the observation period,
      but frequencies of these events did not differ between groups. Event-free
      survival rate tended to be higher in the BCA group than in controls. Among the
      parameters of liver function, serum albumin level was only significantly
      increased over 6 months, and remained at similar values for one year (P < 0.05).
      SF-8 scores for general health, physical functioning, and social functioning were
      significantly elevated in the BCAA group (P < 0.05). Non-protein respiratory
      quotient was significantly improved in the BCAA group (P < 0.01). CONCLUSION:
      Supplementation with BCAA-enriched nutrients for one year in cirrhotic patients
      with HCC after RFA therapy can perform safety and improve both nutritional state
      and quality of life.

PMID- 20796155
TI  - Interobserver and intraobserver variability in evaluating vascular invasion in
      hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is unique in that the presence
      of vascular invasion significantly changes tumor stage. Even though searching for
      vascular invasion is a common practice in surgical pathology, there appears to be
      a great variation among pathologists in its recognition. This study was designed
      to assess whether HCC could be accurately staged using vascular invasion as a
      staging parameter. METHODS: The interobserver and intraobserver agreement for
      vascular invasion was analyzed in 126 liver resections for HCC. Selected slides
      were circulated twice among six pathologists for independent review using their
      own criteria. One to three representative images from 26 equivocal cases selected
      by one of the authors were re-evaluated by the pathologists. The presence or
      absence of vascular invasion on each slide or image was recorded as yes or no.
      The results were analyzed using unweighted kappa statistic analysis for multiple
      raters. RESULTS: The interobserver agreement was moderate on two slide
      circulations with kappa values of 0.50 (95% confidence interval 0.45-0.55) and
      0.43 (0.38-0.47), respectively. The kappa value dropped significantly to 0.19
      (0.09-0.29) on selected images photographed from controversial cases. The
      intraobserver agreement was moderate, with kappa values ranging from 0.23 to 0.56
      (mean = 0.45). CONCLUSIONS: Pathologists can reproducibly recognize vascular
      invasion in many HCC cases but may have difficulty in equivocal cases, which may
      lead to either understaging or overstaging of the tumors. This may have a
      significant impact on prognostic assessment and therapeutic decision making. Our
      observations indicate the need for improved definition for vascular invasion in
      HCC.

PMID- 20796156
TI  - Comparison of transient elastography, serum markers and clinical signs for the
      diagnosis of compensated cirrhosis.
AB  - BACKGROUND AND AIMS: Non-invasive diagnosis of compensated cirrhosis is
      important. We therefore compared liver stiffness by transient elastography, APRI
      score, AST/ALT ratio, hyaluronic acid and clinical signs to determine which
      modality performed best at identifying compensated cirrhosis. METHODS: Patients
      undergoing evaluation at a single center were recruited and had clinical,
      serological, endoscopy, radiological imaging, liver stiffness measurement and
      liver biopsy. Patients were stratified into cirrhotic and non-cirrhotic. RESULTS:
      In 404 patients (124 cirrhosis), transient elastography was diagnostically
      superior to the other modalities yielding an AUC 0.9 +/- 0.04 compared with
      hyaluronic acid (AUC 0.81 +/- 0.04: P < 0.05), clinical signs (AUC 0.74 +/- 0.04:
      P < 0.05), APRI score (AUC 0.71 +/- 0.03: P < 0.05) and AST/ALT ratio (AUC 0.66
      +/- 0.03: P < 0.05). The optimum cut-off for transient elastography was 12 kPa
      giving a sensitivity of 89% and specificity of 87% for cirrhosis. In 238
      hepatitis C patients (87 cirrhosis), transient elastography yielded an AUC 0.899
      +/- 0.02 for cirrhosis and in 166 non-HCV patients (37 cirrhosis) the results
      were similar with an AUC 0.928 +/- 0.03; with transient elastography being
      superior to HA, APRI, AST/ALT and clinical signs for all etiologies of cirrhosis
      (P < 0.05 for all). Importantly, transient elastography was statistically
      superior at identifying cirrhosis in 38 biopsy proven Childs Pugh A cirrhotics
      with no clinical, biochemical or radiological features of cirrhosis or portal
      hypertension (AUC 0.87 +/- 0.04). CONCLUSION: Transient elastography accurately
      identified compensated cirrhosis; a liver stiffness of >12 kPa represents an
      important clinical measurement for the diagnosis of cirrhosis.

PMID- 20796158
TI  - Electromagnetic thermoablation to treat thrombocytopenia in cirrhotic and
      hypersplenic rats.
AB  - BACKGROUND AND AIM: Thrombocytopenia due to hypersplenism is usually a serious
      condition in cirrhotic patients who have undergone invasive procedures. We
      designed a new treatment method using a high-frequency alternating
      electromagnetic force to treat the disease condition in a rat model. METHODS:
      Sprague-Dawley rats were given thioacetamide in drinking water and injected with
      methylcellulose intraperitoneally to create a cirrhotic hypersplenism model.
      Spleen volume was determined using the Carlson method. The Control Group
      consisted of 14 rats, 15 weeks old, that were used to determine the normal
      platelet count and normal spleen size. Experimental Group I, consisting of 15
      rats, received electromagnetic thermoablation of their spleens, after which the
      spleen was returned to the abdomen. Group II consisted of 13 rats, receiving the
      same electromagnetic thermoablation as Group I, but the ablated portion was
      removed. Group III consisted of 14 rats receiving total splenectomies. RESULTS:
      Cirrhotic hypersplenism was confirmed during laparotomy and pathological
      examination. Spleen volume enlarged from 1513 +/- 375 mm(3) (Control Group) to
      7943 +/- 2822 mm(3) (experimental groups). Platelet counts increased from 0.35 +/
      0.21 x 10(6)/mm(3) to 0.87 +/- 0.24 x 10(6)/mm(3) for Group I, from 0.52 +/-
      0.23 x 10(6)/mm(3) to 1.10 +/- 0.20 x 10(6)/mm(3) for Group II, and from 0.47 +/-
      0.23 x 10(6)/mm(3) to 1.18 +/- 0.26 x 10(6)/mm(3) for Group III. No rats died due
      to the treatment in any of the experimental groups. CONCLUSIONS: Our animal model
      performed successfully and our proposed electromagnetic thermotherapy effectively
      treated thrombocytopenia due to cirrhotic hypersplenism.

PMID- 20796157
TI  - Simpler score of routine laboratory tests predicts liver fibrosis in patients
      with chronic hepatitis B.
AB  - BACKGROUND AND AIM: In recent years, a great interest has been dedicated to the
      development of noninvasive predictive models to substitute liver biopsy for
      fibrosis assessment and follow-up. Our aim was to provide a simpler model
      consisting of routine laboratory markers for predicting liver fibrosis in
      patients chronically infected with hepatitis B virus (HBV) in order to optimize
      their clinical management. METHODS: Liver fibrosis was staged in 386 chronic HBV
      carriers who underwent liver biopsy and routine laboratory testing. Correlations
      between routine laboratory markers and fibrosis stage were statistically
      assessed. After logistic regression analysis, a novel predictive model was
      constructed. This S index was validated in an independent cohort of 146 chronic
      HBV carriers in comparison to the SLFG model, Fibrometer, Hepascore, Hui model,
      Forns score and APRI using receiver operating characteristic (ROC) curves.
      RESULTS: The diagnostic values of each marker panels were better than single
      routine laboratory markers. The S index consisting of gamma-glutamyltransferase
      (GGT), platelets (PLT) and albumin (ALB) (S-index: 1000 x GGT/(PLT x ALB(2))) had
      a higher diagnostic accuracy in predicting degree of fibrosis than any other
      mathematical model tested. The areas under the ROC curves (AUROC) were 0.812 and
      0.890 for predicting significant fibrosis and cirrhosis in the validation cohort,
      respectively. CONCLUSIONS: The S index, a simpler mathematical model consisting
      of routine laboratory markers predicts significant fibrosis and cirrhosis in
      patients with chronic HBV infection with a high degree of accuracy, potentially
      decreasing the need for liver biopsy.

PMID- 20796159
TI  - Education and Imaging. Gastrointestinal: massive intraperitoneal haemorrhage in a
      young woman with hereditary hemorrhagic telangiectasia.

PMID- 20796160
TI  - Education and Imaging. Gastrointestinal: collagenous sprue.

PMID- 20796161
TI  - Education and Imaging. Hepatobiliary and pancreatic: imaging for hepatic
      angiomyolipoma.

PMID- 20796162
TI  - Employment impact and financial burden for families of children with fragile X
      syndrome: findings from the National Fragile X Survey.
AB  - BACKGROUND: The employment impact and financial burden experienced by families of
      children with fragile X syndrome (FXS) has not been quantified in the USA.
      METHOD: Using a national fragile X family survey, we analysed data on 1019
      families with at least one child who had a full FXS mutation. Out-of-pocket
      expenditures related to fragile X were reported. We used logistic regression to
      examine the role of insurance, number of affected children, and number of total
      co-occurring conditions in predicting the financial burden and employment impact
      of FXS, while adjusting for race, education, marital status and other
      sociodemographic predictors. RESULTS: Almost half of families affected by FXS
      reported that they had experienced an increased financial burden and nearly 60%
      stated that they had had to change work hours or stop work because of FXS.
      Families with health insurance that met family needs were significantly less
      likely to report an excess financial burden. The type of insurance (private or
      public) was not associated with the reported financial burden. Affected
      children's mutation status, especially male children with the full mutation, was
      associated with employment impact. The total number of co-occurring conditions
      was associated with both financial burden and employment impact. CONCLUSIONS:
      Families affected by FXS experienced a significant employment impact and
      financial burden. Policies designed to help families with FXS need to take into
      consideration the dimension of co-occurring conditions.

PMID- 20796163
TI  - Endovascular abdominal aortic aneurysm repair by interventional cardiologists--a
      community-based experience.
AB  - INTRODUCTION: Endovascular repair of abdominal aortic aneurysm (AAA) is a
      relatively recent technology. In comparison to the conventional open surgical
      treatment for AAA, endovascular AAA repair (EVAR) combines a less-invasive
      approach with lower morbidity and mortality. There have been few studies
      regarding the performance of this procedure in a community-based setting. We
      report our experience of EVAR performed primarily by interventional cardiologists
      in a community hospital. METHODS: In our community hospital setting, between
      September 2005 and November 2007, we included all patients who underwent EVAR by
      interventional cardiologists, with available on-site vascular surgical support.
      Clinical and serial computed angiographic imaging outcomes were followed by a
      retrospective chart review. Data collection tools included demographic and
      clinical characteristics, anatomical aneurysm features, length of stay, peri- and
      postprocedural complications, and mortality. RESULTS: A total of 71 consecutive
      patients had EVAR attempted. The endovascular stent placement was successful in
      67 (93%) patients. Thirty-day mortality in this study was 1 of 71 (1.4%). All
      four procedural failures and the single periprocedural mortality occurred in
      women. Mean follow-up was 12 months. There were a total of six mortalities and
      among these four were women (P <= 0.001); however, multivariate analysis revealed
      loss of significant difference in mortality (P = 0.16). Major complications
      following EVAR were noted in 10 of 71 (14%) patients. CONCLUSION: EVAR can be
      successfully performed by experienced interventional cardiologists with vascular
      surgical support in a community-based setting. In our experience, there is
      acceptable rate of complications and mortality in a carefully selected patient
      population.

PMID- 20796164
TI  - Editorial: protein C and S deficiency as a risk factor for stent thrombosis--when
      a rare disorder can predispose to rare events.

PMID- 20796165
TI  - Transcranial Doppler quantification of residual shunt after percutaneous patent
      foramen ovale closure. Comparison of two devices.
AB  - BACKGROUND: Recurrent paradoxical embolism after catheter-based closure of right
      to-left shunt (RLS) can be related to residual RLS. To improve closure success,
      we need a better understanding of the anatomic and device-related factors
      associated with closure efficacy. METHODS: Patients with cryptogenic neurologic
      events and severe RLS (Valsalva Spencer transcranial Doppler [TCD] grade 5/5+)
      who underwent patent foramen ovale (PFO) closure by either central pin
      (Amplatzer((r)) PFO [A-PFO]) or central occluding (Amplatzer((r)) SO [A-SO])
      devices were evaluated for residual shunt by quantitative TCD evaluation at 3
      months. The findings were correlated with atrial septal aneurysm (ASA), device
      type, and device size. RESULTS: We closed 628 consecutive patients with either
      the A-PFO (n = 327) or A-SO (n = 301) device. The frequency of large defects,
      small defects, and ASA was 12%, 88%, and 44% of cases, respectively. Severe
      residual shunt was detected in 13% of A-PFO and 7% of A-SO recipients (P =
      0.005). This difference was attributable to a much higher frequency of severe
      residual shunt among patients with large defects closed with the A-PFO compared
      to the A-SO device (12 out of 29 [41%] vs. 3 out of 42 [7%], respectively; P <
      0.001). There was no significant difference in device failure frequency for small
      defects. The presence of ASA increased the frequency of severe residual shunt
      compared to those without this feature (36 out of 275 [13%] vs. 28 out of 353
      [8%], respectively; P = 0.046) but did not influence device-related differences.
      CONCLUSIONS: (1) Both noncentering and central occluding closure devices
      effectively reduce RLS after PFO closure. (2) Large PFO defects with or without
      ASA have lower residual shunt grades at 3 months when closed by central occluding
      devices.

PMID- 20796166
TI  - Oral hydration and alkalinization is noninferior to intravenous therapy for
      prevention of contrast-induced nephropathy in patients with chronic kidney
      disease.

PMID- 20796167
TI  - Retroperitoneal hematoma in patients undergoing cardiac catheterization.
AB  - OBJECTIVE: To retrospectively study demographic, clinical and hospital outcomes
      in patients who developed RPH following cardiac catheterization. METHODS: Charts
      of patients with RPH from cardiac catheterization, between January 1, 2000 and
      July 30, 2005 were reviewed and compared with two control groups (Grp-I, 90
      patients with local groin complications and Grp-II, 98 patients with no bleeding
      complications). RESULTS: 31 cases of RPH (0.13%) were identified with 84%
      females. Most common presentation was hypotension (87%) and hemoglobin drop
      (96%). CT scan was the diagnostic modality in 93% cases. The mean body surface
      area in RPH group (1.77 +/- .23) was significantly lower than in control group I
      (1.93 +/- .28) and II (1.98 +/- .27). The use of larger sheath size was
      significantly higher in the RPH group (61.3%) than control groups I (26.7%) and
      II (21.4%). Left groin access was significantly more in RPH group (16.1%) and
      control group I (17.8) than control group II (0%). The use of antiplatelets and
      anticoagulants were significantly higher in the RPH group. 13% of patients with
      RPH were treated surgically. The average hospital stay was 8.6 days, 4.5 days and
      3.5 days and mortality 12.9%, 3.3% and 1% in RPH group, control group I and II
      respectively. CONCLUSION: Our study is the second largest series of RPH following
      cardiac catheterization and predicts female gender, large sheath size, left groin
      access and low body surface area as risk factors for RPH.

PMID- 20796168
TI  - Comparison of risks and clinical predictors of contrast-induced nephropathy in
      patients undergoing emergency versus nonemergency percutaneous coronary
      interventions.
AB  - BACKGROUND: Contrast nephropathy (CIN) increases adverse clinical outcomes. We
      examine risks and clinical predictors of CIN in patients undergoing percutaneous
      coronary intervention (PCI) and effectiveness of prophylactic therapy. METHODS: A
      cohort of 8,798 patients who underwent PCI from May 2000 to April 2008 was
      enrolled. We divided patients into 3 groups. A: STEMI patient undergoing primary
      PCI; B: UA/NSTEMI patients undergoing early PCI; C: Patients without MI
      undergoing elective PCI. Pre-PCI saline hydration was given to group B and C if
      baseline glomerular filtration rate (GFR) <60 ml/min/1.73 m2. RESULTS: Mean age
      was 57.4 years; 35.9% was diabetics. Incidence of CIN were 12.0%, 9.2%, and 4.5%,
      in group A, B and C (P = <0.0005). CIN correlated with higher mortality (15.5%
      vs. 1.3%, P < 0.0005) at 1 month. The important predictors of CIN were age >70,
      female gender, anemia, low systolic BP < 100 mmHg, high creatinine kinase level,
      abnormal LVEF, baseline renal impairment, MI and insulin dependent diabetes.
      Incidence of CIN in patients with GFR >60 were 8.2%, 9.2%, and 4.3% in group A,
      B, and C respectively (p < 0.0005). Incidence of CIN in patients with GFR = 30-60
      were 19.1%, 4.5%, and 2.4% (p < 0.0005) and in patients with GFR < 30 were 34.4%,
      40.0%, and 25.9% (p = 0.510). CONCLUSIONS: Pre-hydration prophylaxis was
      effective in preventing CIN in mild renal impaired patients (GFR 30-60) but are
      less so in more severely renal impaired patients (GFR < 30). STEMI patients
      undergoing primary PCI regardless of baseline GFR were at high risk. Accelerated
      prophylactic regime can be considered in this cohort.

PMID- 20796169
TI  - Synthesis and transport of creatine in the CNS: importance for cerebral
      functions.
AB  - Apart of its well known function of 'energetic buffer' through the
      creatine/phosphocreatine/creatine kinase system allowing the regeneration of ATP,
      creatine has been recently suggested as a potential neuromodulator of even true
      neurotransmitter. Moreover, the recent discovery of primary creatine deficiency
      syndromes, due to deficiencies in L-arginine : glycine amidinotransferase or
      guanidinoacetate methyltransferase (the two enzymes allowing creatine synthesis)
      or in the creatine transporter, has shed new light on creatine synthesis,
      metabolism and transport, in particular in CNS which appears as the main tissue
      affected by these creatine deficiencies. Recent data suggest that creatine can
      cross blood-brain barrier but only with a poor efficiency, and that the brain
      must ensure parts of its needs in creatine by its own endogenous synthesis.
      Finally, the recent years have demonstrated the interest to use creatine as a
      neuroprotective agent in a growing number of neurodegenerative diseases,
      including Parkinson's and Huntington's diseases. This article aims at reviewing
      the latest data on creatine metabolism and transport in the brain, in relation to
      creatine deficiencies and to the potential use of creatine as neuroprotective
      molecule. Emphasis is also given to the importance of creatine for cerebral
      function.

PMID- 20796170
TI  - The Reck tumor suppressor protein alleviates tissue damage and promotes
      functional recovery after transient cerebral ischemia in mice.
AB  - The extracellular matrix (ECM) is important for both structural integrity and
      functions of the brain. Matrix metalloproteinases (MMPs) play major roles in ECM
      remodeling under both physiological and pathological conditions. Reversion
      inducing cysteine-rich protein with Kazal motifs (Reck) is a membrane-anchored
      MMP-regulator implicated in coordinated regulation of pericellular proteolysis.
      Although patho-physiological importance of MMPs and another group of MMP
      regulators, tissue inhibitor of metalloproteinases, in brain ischemia has been
      demonstrated, little is known about the role of Reck in this process. In this
      study, we found that Reck is up-regulated in hippocampus and penumbra of
      subventricular zone after transient cerebral ischemia in mice. Most of the Reck
      positive cells found at day 2 after ischemia are positive for Nestin as well as
      Ki67 and localized to the CA2 region of the hippocampus. At day 7 after ischemia,
      the Reck-positive cells increased in number, extended processes, expressed the
      reactive astrocyte marker GFAP and the neuronal marker NF200, and were widely
      distributed in the hippocampus. In the mutant mice carrying single functional
      Reck allele (Reck+/-), tissue damage and cell death after cerebral ischemia were
      augmented, the recovery of long-term potentiation in the hippocampus was
      compromised, NR2C subunit of NMDA receptor was up-regulated, gelatinolytic
      activity of MMPs were up-regulated and laminin-immunoreactivity was reduced. Our
      data implicate Reck in protection of ECM/tissue integrity and promotion of
      functional recovery in the brain after transient cerebral ischemia.

PMID- 20796171
TI  - 5-HT2C receptor activation prevents stress-induced enhancement of brain 5-HT
      turnover and extracellular levels in the mouse brain: modulation by chronic
      paroxetine treatment.
AB  - Stress is known to activate the central 5-hydroxytryptamine (5-HT) system, and
      this is probably part of a coping response involving several 5-HT receptors.
      Although 5-HT(2C) receptors are well known to be implicated in anxiety, their
      participation in stress-induced changes had not been investigated in parallel at
      both behavioral and neurochemical levels. We show here that the preferential 5
      HT(2C) receptor agonist, m-chlorophenylpiperazine, as well as restraint stress
      increased anxiety in the mouse social interaction test. The selective 5-HT(2C)
      receptor antagonist, SB 242,084, prevented both of these anxiogenic effects.
      Restraint stress increased 5-HT turnover in various brain areas, and this effect
      was prevented by the 5-HT(2B/2C) receptor agonist RO 60-0175 (1 mg/kg), but not
      the preferential 5-HT(2A) agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
      (1 mg/kg), and in contrast potentiated by SB 242,084 (1 mg/kg), which also
      blocked the effect of RO 60-0175. Using microdialysis, RO 60-0175 was shown to
      inhibit cortical 5-HT overflow in stressed mice when 5-HT reuptake was blocked
      locally. Chronic paroxetine prevented both the anxiogenic effect of m
      chlorophenylpiperazine and the inhibitory effect of RO 60-0175 on locomotion and
      stress-induced increase in 5-HT turnover. The anxiolytic action of chronic
      paroxetine might be associated with an enhancement of 5-HT neurotransmission
      caused by a decreased 5-HT(2C) receptor-mediated inhibition of stress-induced
      increase in 5-HT release.

PMID- 20796172
TI  - The E3-ubiquitin ligase TRIM2 regulates neuronal polarization.
AB  - The establishment of a polarized morphology with a single axon and multiple
      dendrites is an essential step during neuronal differentiation. This cellular
      polarization is largely depending on changes in the dynamics of the neuronal
      cytoskeleton. Here, we show that the tripartite motif (TRIM)-NHL protein TRIM2 is
      regulating axon specification in cultured mouse hippocampal neurons, where one of
      several initially indistinguishable neurites is selected to become the axon.
      Suppression of TRIM2 by RNA interference results in the loss of neuronal polarity
      while over-expression of TRIM2 induces the specification of multiple axons. TRIM2
      conducts its function during neuronal polarization by ubiquitination of the
      neurofilament light chain. Together, our results imply an important function of
      TRIM2 for axon outgrowth during development.

PMID- 20796173
TI  - Subcellular rearrangement of hsp90-binding immunophilins accompanies neuronal
      differentiation and neurite outgrowth.
AB  - FKBP51 and FKBP52 (FK506-binding protein 51 and 52) are tetratricopeptide repeat
      domain immunophilins belonging to the tetratricopeptide-protein*hsp90*hsp70*p23
      heterocomplex bound to steroid receptors. Immunophilins are related to receptor
      folding, subcellular localization, and hormone-dependent transcription. Also,
      they bind the immunosuppressant macrolide FK506, which shows neuroregenerative
      and neuroprotective actions by a still unknown mechanism. In this study, we
      demonstrate that in both, undifferentiated neuroblastoma cells and embryonic
      hippocampal neurons, the FKBP52*hsp90*p23 heterocomplex concentrates in a
      perinuclear structure. Upon cell stimulation with FK506, this structure
      disassembles and this perinuclear area becomes transcriptionally active. The
      acquisition of a neuronal phenotype is accompanied by increased expression of
      betaIII-tubulin, Map-2, Tau-1, but also hsp90, hsp70, p23, and FKBP52. During the
      early differentiation steps, the perinuclear heterocomplex redistributes along
      the cytoplasm and nascent neurites, p23 binds to intermediate filaments and
      microtubules acquired higher filamentary organization. While FKBP52 moves towards
      neurites and concentrates in arborization bodies and terminal axons, FKBP51,
      whose expression remains constant, replaces FKBP52 in the perinuclear structure.
      Importantly, neurite outgrowth is favored by FKBP52 over-expression or FKBP51
      knock-down, and is impaired by FKBP52 knock-down or FKBP51 over-expression,
      indicating that the balance between these FK506-binding proteins plays a key role
      during the early mechanism of neuronal differentiation.

PMID- 20796174
TI  - Therapeutic evaluation of etanercept in a model of traumatic brain injury.
AB  - Antagonism of tumor necrosis factor-alpha with etanercept has proved to be
      effective in the treatment of spinal cord injury and centrally endotoxin-induced
      brain injury. However, etanercept may offer promise as therapy for traumatic
      brain injury (TBI). In this study, anesthetized rats, immediately after the onset
      of TBI, were divided into two major groups and given the vehicle solution (1
      mL/kg of body weight) or etanercept (5 mg/kg of body weight) intraperitoneally
      once per 12 h for consecutive 3 days. Etanercept caused attenuation of TBI
      induced cerebral ischemia (e.g., increased cellular levels of glutamate and
      lactate-to-pyruvate ratio), damage (e.g., increased cellular levels of glycerol)
      and contusion and motor and cognitive function deficits. TBI-induced neuronal
      apoptosis (e.g., increased numbers of terminal deoxynucleotidyl transferase
      alphaUTP nick-end labeling and neuronal-specific nuclear protein double-positive
      cells), glial apoptosis (e.g., increased numbers of terminal deoxynucleotidyl
      transferase alphaUTP nick-end labeling and glial fibrillary acidic protein double
      positive cells), astrocytic (e.g., increased numbers of glial fibrillary acidic
      protein positive cells) and microglial (e.g., increased numbers of ionized
      calcium-binding adapter molecule 1-positive cells) activation and activated
      inflammation (e.g., increased levels of tumor necrosis factor-alpha, interleukin
      1beta and interleukin-6) were all significantly reduced by etanercept treatment.
      These findings suggest that etanercept may improve outcomes of TBI by penetrating
      into the cerebrospinal fluid in rats.

PMID- 20796175
TI  - Hyperdopaminergic tone in HIV-1 protein treated rats and cocaine sensitization.
AB  - In the United States, one-third of infected individuals contracted Human
      Immunodeficiency Virus-1 (HIV-1) via injecting drugs with contaminated needles or
      through risky behaviors associated with drug use. Research demonstrates
      concomitant administration of psychostimulants and HIV-1-proteins damage neurons
      to a greater extent than viral proteins or the drug alone. To model the onset of
      HIV-1-infection in relation to a history of drug use, the current research
      compared behavior and extracellular dopamine and metabolite levels following
      Tat(1-86) infusions in animals with and without a history of cocaine (Coc)
      experience (10 mg/kg; i.p.; 1 injection/day * 9 days). Animals receiving a
      behaviorally sensitizing regimen of Coc demonstrated a decrease in extracellular
      dopamine concentration in the nucleus accumbens, consistent with evidence
      describing up-regulation of dopamine transporter uptake. Contrary to this effect,
      Tat(1-86) microinfusion into the nucleus accumbens following the sensitizing
      regimen of Coc caused a significant increase in extracellular dopamine levels
      (nM) within 48 h with no difference in percent of baseline response to Coc. After
      72 h, Tat + Coc treated animals demonstrated a blunted effect on potassium
      stimulated extracellular dopamine release (percent of baseline) with a
      corresponding decrease in expression of behavioral sensitization to Coc
      challenge. A persistent decrease in extracellular dopamine metabolite levels was
      found across all time-points in Tat-treated animals, regardless of experience
      with Coc. The current study provides evidence for divergent neurochemical and
      behavioral outcomes following Tat-treatment; contingent upon experience with Coc.

PMID- 20796176
TI  - Quantitative analysis of the heteromeric neuronal nicotinic receptors in the rat
      hippocampus.
AB  - The objective of this study was to identify and quantify the heteromeric neuronal
      nicotinic receptors (nAChRs) in the rat hippocampus. The density of nAChR
      subtypes was assessed by labeling them with [(3)H]epibatidine ([(3)H]EB) followed
      by immunoprecipitation with subunit-selective antibodies. Sequential
      immunoprecipitation assays were used to establish associations between two
      different subunits, which then allowed the full subunit composition of the
      receptors to be deduced. Our results show that most of the hippocampal
      heteromeric nAChRs contain alpha4 and beta2 subunits. In fact, we identified two
      populations containing these two predominant subunits, the alpha4beta2 and
      alpha4beta2alpha5 subtypes which account for ~ 40% and ~ 35%, respectively, of
      the total [(3)H]EB-labeled receptors. An additional heteromeric subtype with the
      subunit composition of alpha4beta2alpha3 represented ~ 10% of the total nAChRs,
      and another 10% of the immunoprecipitated receptors contained alpha4 and beta4
      subunits, with or without the alpha3 subunit. To determine if alpha4beta2 and
      alpha4beta2alpha5 nAChR subtypes differ in their ligand binding affinities, the
      alpha3- and beta4-containing receptors were first removed by immunoprecipitation
      and then, competition studies with acetylcholine, nicotine, cytisine and
      sazetidine-A against [(3)H]EB were carried out on the remaining alpha4beta2 and
      alpha4beta2alpha5 subtypes. Results suggested these subtypes have comparable
      binding affinities for the nicotinic ligands used here.

PMID- 20796178
TI  - Assisted exercise improves bone strength in very low birthweight infants by bone
      quantitative ultrasound.
AB  - AIM: To evaluate whether assisted exercise could prevent the development of
      osteopenia of prematurity, we performed assisted exercise in the study group of
      very low birthweight (VLBW) premature infants. METHODS: Sixteen premature infants
      with birthweight below 1500 g were enrolled in this study and randomly assigned
      into the exercise (n = 8) and control (n = 8) groups. Assisted exercise involved
      full extension and flexion range of motion of the upper and lower extremities by
      a trained nurse with a schedule of 5 days a week for a total of 4 weeks. Bone
      strength was determined by quantitative ultrasound measurement of tibial bone
      speed of sound every 2 weeks during the study period. RESULTS: No difference in
      gender, birthweight, and gestation age between the exercise and control groups
      was noted. There was statistically significant less tibial bone speed of sound
      decrease in the exercise group on the sixth and eighth week of life. During the
      study period, there were no statistically significant differences in blood
      biochemistry data, including calcium, phosphorus, magnesium, alkaline
      phosphatase, osteocalcin and osteoprotegerin, between the two groups.
      CONCLUSIONS: This study revealed that early assisted exercise could improve bone
      strength in very low birthweight infants. The biochemical markers of bone
      metabolism, osteocalcin and osteoprotegerin, could not be the indicators for
      early diagnosis of osteopenia of prematurity.

PMID- 20796177
TI  - Acidification of the Golgi apparatus is indispensable for maturation but not for
      cell surface delivery of Ret.
AB  - We examined the effect of concanamycin A and bafilomycin A1, inhibitors of the
      vacuolar proton-ATPase, on maturation and expression of Ret, a tyrosine kinase
      receptor for glial cell line-derived neurotrophic factor. Ret appeared as 150-
      and 170-kDa bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      gels and both forms were sensitive to peptide-N-glycosidase F. Western and
      immunocytochemical analyses revealed that the 150-kDa immature form of Ret
      accumulated in the Golgi apparatus upon treatment with vacuolar proton-ATPase
      inhibitors, whereas, the 170-kDa mature form of Ret was dramatically decreased.
      The result suggests that glycosylation of Ret during the conversion from immature
      forms to mature forms is pH sensitive, and is likely initiated in the acidic
      trans-Golgi apparatus. In contrast, glycosylation of nascent receptors to become
      immature receptors appeared to be pH insensitive, and are likely to take place in
      the endoplasmic reticulum. The immature form of Ret was present in the plasma
      membrane when the cells were treated with the vacuolar proton-ATPase inhibitors.
      In conclusion, the acidification of the Golgi apparatus is crucial for maturation
      of Ret but not indispensable for trafficking of receptors to the membrane.

PMID- 20796179
TI  - Diagnosing daytime bladder symptoms in children with nocturnal enuresis: a
      comparison of brief parental questionnaire with in-depth, physician-elicited,
      assessment.
AB  - AIMS: To assess the accuracy of brief parental questionnaire reporting of daytime
      bladder symptoms in children with nocturnal enuresis and compare with in-depth
      reporting elicited by physician assessment, for diagnosing monosymptomatic and
      non-monosymptomatic nocturnal enuresis. METHODS: A cross-sectional study of
      consecutive children attending an outpatient nocturnal enuresis clinic at a
      tertiary paediatric hospital participated in the study. Parents were asked to
      complete a questionnaire as part of routine assessment at their first visit which
      was compared with a detailed clinical assessment by the physician involving
      eliciting a thorough history from the parent and child. RESULTS: Parents of 585
      children participated in the study (mean age 9.2 years, range 5.0-17.5 years).
      Sixty percent of children were males. There was poor agreement between initial
      parental reporting and physician diagnosis of monosymptomatic and non
      monosymptomatic nocturnal enuresis (Kappa = 0.3, 95% confidence interval 0.21
      0.37), mainly because parents underreport daytime incontinence and urgency
      compared with physician-elicited information (43% vs. 69% and 66% vs. 87%,
      respectively). CONCLUSIONS: Parents underreport daytime symptoms by 20-25%.
      Reliance on a brief parental history without prompting by physicians for daytime
      symptoms for diagnosing type of nocturnal enuresis may be misleading and result
      in suboptimal management.

PMID- 20796180
TI  - Perception, attitudes and knowledge regarding the 2009 swine-origin influenza A
      (H1N1) virus pandemic among health-care workers in Australia.
AB  - AIM: To determine the perceptions, attitudes and knowledge of Australian health
      care workers (HCWs) regarding the novel, swine-origin influenza A (H1N1) virus (S
      OIV) outbreak that reached the country in early May 2009. METHODS: Self
      administered, anonymous Web-based survey conducted during the early stages of the
      S-OIV pandemic. Participants comprised hospital- and community-based medical and
      nursing staff, medical students, allied health professionals, laboratory staff
      and administrative personnel. RESULTS: Of the 947 participants surveyed, 59.4%
      were not convinced that Australia was sufficiently prepared for an influenza
      pandemic. Only 17.6% of the participants stated they were prepared to work
      unconditionally during a pandemic; 36.5% stated they would work if they had
      access to antiviral treatment; 27.9% would if provided with antiviral
      prophylaxis; and 7.5% would refuse to work. In addition, 37.5% of the
      participants responded they would refuse or avoid being involved in screening
      suspected cases. A total of 47.7% admitted to possessing a personal supply of
      antivirals or having considered this option. Only 48.0% provided a realistic
      estimate of the mortality associated with an influenza pandemic at a population
      level. HCWs overestimating the mortality risk and HCWs believing the efficacy of
      antiviral prophylaxis to be low were significantly less likely to be prepared to
      work (P= 0.04 and P= 0.0004, respectively). CONCLUSIONS: To ensure adequate
      staffing during an influenza pandemic, preparedness plans should anticipate
      significant levels of absenteeism by choice. Interventions aimed at increasing
      staff retention during a pandemic require further evaluation.

PMID- 20796181
TI  - Relationship between birth head circumference and adulthood quality of life in
      Chinese people.
AB  - AIM: To determine the relationship between birth size and later QOL for Chinese
      people. METHODS: Birth data of 1074 subjects were obtained from obstetric birth
      records of Peking Union Medical College Hospital. All subjects are interviewed
      face to face with the 36-Item Short-Form Health Survey scale by trained
      investigators. Linear regression model was used to analyse the relationship
      between QOL and birth head circumference of the subjects after adjusting for the
      childhood and adulthood characteristics. The relationship was described with
      regression coefficients (B) and its 95% confidence interval (CI). RESULTS: The
      mean weighted score of QOL was 88.1 +/- 9.1, ranging from 76.8 to 100. Larger
      birth head circumference meant higher adulthood QOL total score (P= 0.001). After
      controlling the adulthood confounders, as compared to larger head circumference
      (>=33 cm), small (<31 cm) and medium head circumferences (31-33 cm) meant lower
      adulthood QOL scores (B=-2.356, P= 0.005 and B=-1.645, P= 0.014, respectively).
      The increase of head circumference by 1 cm was associated with 0.480 (95% CI:
      0.141, 0.820) increase of QOL score after adjusting adulthood confounders (P=
      0.006). CONCLUSIONS: This study validated the relationship between birth head
      circumference and QOL in later life. Smaller head circumference at birth could
      predict worse adulthood QOL at above 50 years old.

PMID- 20796182
TI  - Interpersonal violence hospitalisations for adolescents: a population-based
      study.
AB  - AIM: To investigate the incidence and nature of interpersonal violence
      hospitalisations for victims aged 11-18 years and to identify subgroups at risk
      of repeat hospital admissions. METHODS: A population-based, retrospective study
      of interpersonal violence from 1990 to 2004 was undertaken, using linked hospital
      morbidity and mental health records for adolescents in Western Australia.
      RESULTS: A total of 3607 adolescents incurred 4094 violence hospitalisations
      during the study period. Of this cohort, 2992 (83%) were between 15 and 18 years
      of age. Younger victims aged 11-14 years with a previous mental illness admission
      were at increased risk of a subsequent hospitalisation for violence when compared
      to those without (hazard ratio (HR) 2.81, 95% confidence interval (CI) 1.83
      4.31). Adolescents aged 15-18 years were at increased risk to incur a second
      violence episode if they were female (HR 1.46, 95% CI 1.23-1.75), Indigenous (HR
      1.83, 95% CI 1.51-2.22), living in rural (HR 1.60, 95% CI 1.26-2.04) or remote
      areas (HR 1.96, 95% CI 1.56-2.47) and had a previous mental illness admission (HR
      1.56, 95% CI 1.30-1.86). CONCLUSIONS: The identification of victim subgroups at
      high risk of repeat hospitalisations is important for preventing interpersonal
      violence. Adolescents with a mental illness should be specifically targeted for
      attention.

PMID- 20796183
TI  - The social determinants of early child development: an overview.
AB  - AIM: This paper offers an overview of the current state of knowledge of the
      critical social determinants of child development and the complex ways in which
      these can influence health trajectories. METHODS: We conducted an overview of the
      research conducted by medical and social scientists in the attempt to uncover the
      conditions under which children reach optimal health and developmental. RESULTS:
      The first years of life represent a critical period during which trajectories of
      health vulnerability are determined by the complex interplay between biological,
      genetic, and environmental conditions. CONCLUSIONS: There are fundamental
      principles of optimal child development that apply to all human beings,
      regardless of language and culture.

PMID- 20796184
TI  - Parent-perceived barriers to participation in children and adolescents with
      cerebral palsy.
AB  - AIM: To pilot the use of the Craig Hospital Inventory of Environmental Factors
      (CHIEF) questionnaire to ascertain information regarding barriers to
      participation experienced by a sample of New Zealand children with cerebral
      palsy. METHODS: The CHIEF questionnaire was administered to parents/caregivers of
      a consecutive sample of 32 children with cerebral palsy attending a paediatric
      tertiary clinic in Auckland. Twenty-three children walked independently, 5 used
      walking aides and four used a wheelchair. Twenty-four of the 32 parent
      respondents provided contextual feedback for their responses and wider issues
      relating to the topic. RESULTS: The barriers to participation most commonly
      reported by parents were attitudes at school (72%) and in the community (56%),
      difficulties accessing personal equipment (59%), and the natural environment and
      built surroundings (56%). Contextual information from families generally
      supported their answers to the questionnaire but highlighted that some parents
      had confused the 'not applicable' and 'never' options. Discrepancy between scores
      on the policy-related questions and later contextual feedback suggested that the
      policy subscale did not fully capture family concerns about limited availability
      of public funding for equipment, therapy, and educational support. CONCLUSIONS:
      The CHIEF instrument proved easy to use in a clinic setting. However, parent
      respondent feedback highlighted the difficulties in interpreting responses to
      some items when the instrument is used in isolation to quantify environmental
      barriers to participation. The results highlight the need to develop research
      approaches and tools that can explore barriers to participation by children with
      cerebral palsy taking account of socio-economic and other relevant contextual
      information.

PMID- 20796185
TI  - Neonatal community-acquired pneumonia: pathogens and treatment.
AB  - AIM: To analyse the bacterial pathogens and drug sensitivities for neonatal
      community-acquired pneumonia. METHODS: Seven hundred sixty sputum samples from
      newborns with community-acquired pneumonia were cultured to determine microbial
      organisms present and their drug sensitivities. RESULTS: Of the 760 specimens,
      425 grew pathogens for a 55.9% positive rate. Among the 425 positive cultures,
      278 grew gram-negative organisms (65.4%), 142 grew gram-positive organisms
      (33.3%), while 5 grew fungus (1.3%). The most common gram-negative organisms were
      Escherichia coli, Klebsiella pneumoniae and Hemophilus influenzae, while the most
      common gram-positive organisms were Staphylococcus aureus, Staphylococcus
      epidermidis and Staphylococcus haemolyticus. To the gram-negative organisms, the
      most sensitive drugs were meropenem, imipenem and amikacin, while to the gram
      positive ones were vancomycin, teicoplanin and quinupristin/dalfopristin.
      CONCLUSIONS: The most common causative bacteria were gram-negative organisms,
      which were highly sensitive to Meropenem, Imipenem and Amikacin, yet often
      treatable with more focused antibiotic coverage, which depended on the bacterium
      identified.

PMID- 20796186
TI  - Ion channels as novel therapeutic targets in the treatment of pain.
AB  - OBJECTIVES: This review considers ion channels as potential novel therapeutic
      targets, particularly in the treatment of pain. KEY FINDINGS: Ion channel
      proteins underlie electrical signalling throughout the body and are important
      targets for existing therapeutic agents. Nevertheless, ion channels remain a
      relatively underexploited family of proteins for therapeutic interventions. A
      number of recent advances in both technology and knowledge suggest that these
      proteins are promising targets for future therapeutic development. For example,
      there has been considerable recent improvement in high-throughput screening
      technologies following the need for pharmaceutical companies to screen against
      compounds which block human ether-a-go-go-related gene (hERG) potassium channels.
      Similarly an increased awareness of the importance of ion channels in disease
      states such as epilepsy, ataxia, cardiac arrhythmia, diabetes and cystic fibrosis
      has been revealed through studies of genetic mutations in humans and genetic
      ablation studies in animals. Furthermore, recent advances in the understanding of
      ion channel structure and how this relates to their function has provided
      significant new insights into where exactly on the ion channel protein novel
      therapeutic agents might be developed to target. In the particular area of pain
      research a number of different ion channel subtypes have been identified
      (including certain sodium, potassium and transient receptor potential (TRP)
      channels). SUMMARY: It seems likely that new therapies will arise that target ion
      channels. In the treatment of pain, for example, novel agents targeting TRPV1
      channels are already showing considerable therapeutic promise.

PMID- 20796187
TI  - Combined strategies for enhancing the transdermal absorption of midazolam through
      human skin.
AB  - OBJECTIVES: Midazolam administration by intravenous or intramuscular injection
      produces pain and stress. For this reason, alternative methods of administration
      have been proposed. The transdermal administration of midazolam could improve
      patient comfort, which is especially important for children in the pre-operative
      period. We aimed to assess the effect of iontophoresis and chemical percutaneous
      enhancers applied individually and together, to determine if a synergistic effect
      is achieved when both enhancement techniques are simultaneously employed.
      METHODS: This work reports the characterization of the passive diffusion of
      midazolam hydrochloride through human skin in vitro and evaluates the effect of
      iontophoresis application and chemical percutaneous enhancers on said diffusion
      when employed both individually and in combination. KEY FINDINGS: Percutaneous
      absorption assays demonstrated that the physical technique of iontophoresis, when
      applied alone, moderately increased midazolam hydrochloride permeation flux
      through human skin, producing a similar effect to that obtained with R-(+)
      limonene chemical enhancer. Among the strategies assayed, it was observed that
      Azone produced the most pronounced enhancement effect when applied separately.
      The combination of pre-treatment with Azone and iontophoresis exhibited a higher
      capacity for enhancing the transdermal flux of midazolam through human skin than
      Azone alone. CONCLUSIONS: In conclusion, when applied individually, Azone
      exhibited the greatest enhancement effect on the transdermal diffusion of
      midazolam of the various strategies assayed. The combination of Azone and
      iontophoresis produce the highest transdermal steady-state flux of midazolam but
      no synergic effect was achieved when the two enhancement strategies were applied
      in combination, showing that although selecting the best conditions for
      iontophoresis application, it is less effective for augmenting the transdermal
      delivery of midazolam than the chemical enhancer Azone.

PMID- 20796188
TI  - Development of nanosomes using high-pressure homogenization for gene therapy.
AB  - OBJECTIVES: The aim of this project was to develop a novel lipid-based
      formulation suitable for gene therapy. METHODS: Novel nanosize liposome
      (nanosome) formulations containing pDNA (plasmid DNA) were developed using high
      pressure homogenization (HPH). The effect of lipid concentration was studied at
      two levels: 3 mm and 20 mm. The preformed nanosomes were incubated for 18-20 h
      with pDNA or pDNA/protamine sulfate (PS) complex. The physical properties of the
      pDNA nanosomes were compared by particle size distribution and zeta-potential
      measurements. Their biological properties were also compared by pDNA efficiency
      of encapsulation/complexation, integrity, nuclease digestion, transfection
      efficiency and cell cytotoxicity. KEY FINDINGS: pDNA nanosomes prepared with 20
      mM lipid (nanosomes:pDNA:PS at a ratio of 8.6:1:2) had particle sizes of 170-422
      nm (90% confidence). The zeta-potential of the formulation was 49.2 +/- 1.5 mV,
      and the pDNA encapsulation/complexation efficiency was approximately 98%. pDNA
      nanosomes prepared with 3 mM lipid (nanosomes:pDNA PS at a ratio of 2.09:1:2) had
      particle sizes of 140-263 nm (90% confidence). The zeta-potential of this
      formulation was 36.4 +/- 1.2 mV, and the pDNA encapsulation/complexation
      efficiency was approximately 100%. However, a comparison of the efficiency of
      transfection indicated that pDNA nanosomes prepared with low-concentration lipids
      (3 mM) showed significantly higher transfection efficiency compared with the pDNA
      nanosomes prepared with high-concentration lipids (20 mM), as well as those
      prepared with Fugene-6 (a commercially available transfection reagent). This
      particular formulation (pDNA nanosomes, 3 mM lipids) also showed significantly
      less cytotoxicity compared with the other pDNA nanosome formulations.
      CONCLUSIONS: To conclude, these results indicate that condensing pDNA with PS
      followed by subsequent complexation with low-concentration nanosomes generated
      from HPH can produce a pDNA nanosome formulation that will boost transfection
      efficiency, while minimizing cytotoxicity. This new technology appears to be an
      efficient tool for future commercial or large-scale manufacture of DNA delivery
      systems for gene therapy.

PMID- 20796189
TI  - Development and oral bioavailability assessment of a supersaturated self
      microemulsifying drug delivery system (SMEDDS) of albendazole.
AB  - OBJECTIVES: Albendazole's (ABZ) poor aqueous solubility is a major determinant of
      its variable therapeutic response (20-50%). The purpose of this study was to
      develop and optimize the composition of a self-microemulsifying drug delivery
      system (SMEDDS) of ABZ and assess its oral pharmacokinetics in rabbits. METHODS:
      A D-optimal mixture design of experiments was used to select the levels of
      constraints of the formulation variables. The predicted composition was optimized
      using four responses: dispersion performance, droplet sizes, dissolution
      efficiency (DE) and time for 85% drug release (t(85%)). KEY FINDINGS: The optimal
      composition of the ABZ-SMEDDS formulation, with approximately 5 mg/g drug loading
      of ABZ, was predicted to be Cremophor EL (30% w/w), Tween 80 (15% w/w), Capmul PG
      8 (10% w/w) and acidified PEG 400 (45% w/w). An increase of 63% in the relative
      bioavailability compared with the commercial suspension was obtained with ABZ
      SMEDDS as measured by albendazole sulfoxide (ABZSO) plasma levels. The area under
      the curve (AUC(0-->24h)) and the peak plasma concentration (C(max)) of ABZ-SMEDDS
      was higher than those obtained with the commercial suspension by 56% and 52%,
      respectively. CONCLUSIONS: This study demonstrates a strategy for the development
      of a supersaturated SMEDDS formulation of a drug with low aqueous solubility.

PMID- 20796190
TI  - Evidence of the involvement of K+ channels and PPARgamma receptors in the
      antidepressant-like activity of diphenyl diselenide in mice.
AB  - OBJECTIVES: This study investigated the involvement of different types of K(+)
      channels and PPARgamma receptors in the antidepressant-like effect of diphenyl
      diselenide in mice. METHODS: Mice were pretreated with subeffective doses of K(+)
      channel inhibitors (tetraethylammonium, glibenclamide, charybdotoxin and apamin),
      openers (cromakalim, minoxidil), GW 9662 (a PPARgamma antagonist) or vehicle.
      Thirty minutes later the mice received diphenyl diselenide in either an effective
      or a subeffective dose, 30 min before a tail-suspension test. KEY FINDINGS: Pre
      treatment with tetraethylammonium, charybdotoxin or apamin combined with a
      subeffective dose of diphenyl diselenide was effective in decreasing the
      immobility time in the mouse tail-suspension test. The reduction in the
      immobility time elicited by an effective dose of diphenyl diselenide in this test
      was prevented by the pretreatment of mice with minoxidil and GW 9662.
      CONCLUSIONS: Diphenyl diselenide elicited an antidepressant-like effect and this
      action was mediated, at least in part, by modulation of K(+) channels and
      PPARgamma receptors.

PMID- 20796191
TI  - Induction of apoptosis and cell cycle arrest in L-1210 murine lymphoblastic
      leukaemia cells by (2E)-3-(2-naphthyl)-1-(3'-methoxy-4'-hydroxy-phenyl)-2-propen
      1-one.
AB  - OBJECTIVES: New compounds with biological targets and less cytotoxicity to normal
      cells are necessary for cancer therapy. In this work ten synthetic chalcones
      derived from 2-naphtaldehyde were evaluated for their cytotoxic effect in murine
      acute lymphoblastic leukemia cells L-1210. METHODS: A series of ten chalcones
      derived from 2-naphtaldehyde and corresponding acetophenones were prepared by
      aldolic condensation, using methanol as solvent under basic conditions, at room
      temperature for 24 h. The cell viability was determined by MTT colorimeter
      method. The cell cycle phase analysis was carried out by flow cytometry after
      propidium iodide staining. The apoptosis induction was assessed by exposure to
      phosphatidylserine (ANNEXIN V-FITC). Cytometric analysis was performed to
      evaluate the expression of p53, Bcl-2 and Bax protein. The caspase-3 expression
      was studied by immunoblotting analysis. KEY FINDINGS: A preliminary screening of
      a series of ten chalcones derived from 2-naphtaldehyde showed that chalcone 8,
      (2E)-3-(2-naphtyl)-1-(3'-methoxy-4'-hydroxy-phenyl)-2-propen-1-one, had the
      highest cytotoxic effect (IC50 of 54 microM), but not in normal human
      lymphocytes. To better understand the cytotoxic mechanism of chalcone 8, its
      effect on cell cycle and apoptosis was assessed. Our results showed that chalcone
      8 caused cell cycle arrest in the G2/M phase and a significant increase in the
      proportion of cells in the subG0/G1 phase. Our results also demonstrated that
      chalcone 8 promoted a modification in Bax:Bcl-2 ratio and increased p53
      expression and caspase-3 activation. CONCLUSIONS: The studied chalcone 8 has
      cytotoxic effect against L-1210 lymphoblastic leukaemic cells, and this effect is
      associated with increase of p-53 and Bax expression.

PMID- 20796192
TI  - Anti-pigmentary activity of fucoxanthin and its influence on skin mRNA expression
      of melanogenic molecules.
AB  - OBJECTIVES: Carotenoids and retinoic acid derivatives are topically applied for
      sun-protective and whitening purposes. Fucoxanthin is a carotenoid derived from
      edible sea algae, but its effect on melanogenesis has not been established.
      Therefore, we examined the effect of fucoxanthin on melanogenesis. METHODS:
      Inhibitory effects on tyrosinase activity, melanin formation in B16 melanoma and
      skin pigmentation in UVB-irradiated guinea-pigs were evaluated. To elucidate the
      action of fucoxanthin on melanogenesis, its effect on skin melanogenic mRNA
      expression was evaluated in UVB-irradiated mice. Fucoxanthin was given topically
      or orally to mice once a day and UVB irradiation was applied for 14 days. The
      effect of fucoxanthin on skin melanogenic mRNA expression was evaluated by real
      time reverse transcription polymerase chain reaction. KEY FINDINGS: Fucoxanthin
      inhibited tyrosinase activity, melanogenesis in melanoma and UVB-induced skin
      pigmentation. Topical application of fucoxanthin (1%) significantly suppressed
      mRNA expression of cyclooxygenase (COX)-2, endothelin receptor A, p75
      neurotrophin receptor (NTR), prostaglandin E receptor 1 (EP1), melanocortin 1
      receptor (MC1R) and tyrosinase-related protein 1. The suppression of p75NTR, EP1
      and MC1R expressions was observed at 0.01% application. Also, oral application of
      fucoxanthin (10 mg/kg) significantly suppressed expression of COX-2, p75NTR, EP1
      and MC1R. CONCLUSIONS: These results suggest that fucoxanthin exhibits anti
      pigmentary activity by topical or oral application in UVB-induced melanogenesis.
      This effect of fucoxanthin may be due to suppression of prostaglandin (PG) E(2)
      synthesis and melanogenic stimulant receptors (neurotrophin, PGE(2) and
      melanocyte stimulating hormone expression).

PMID- 20796193
TI  - Diphenyl diselenide in its selenol form has dehydroascorbate reductase and
      glutathione S-transferase-like activity dependent on the glutathione content.
AB  - OBJECTIVES: The antioxidant action of diphenyl diselenide ((PhSe)(2)) is
      attributed to the mechanism by which (PhSe)(2) has pharmacological activity.
      Although (PhSe)(2) has glutathione peroxidase mimetic activity, the exact
      mechanism involved in its antioxidant effect has not yet been completely
      elucidated. In the present study, mechanisms involved in the antioxidant property
      of (PhSe)(2) (1-50 microM) were investigated. METHODS: Dehydroascorbate (DHA)
      reductase- and glutathione S-transferase (GST)-like activity, 2,2'-diphenyl-1
      picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)
      (ABTS) radical-scavenging activity and the protection against the oxidation of
      Fe(2+) were evaluated. KEY FINDINGS: (PhSe)(2) at concentrations equal to, or
      greater than, 5 microM showed DHA reductase- and GST-like activity. (PhSe)(2) was
      not a scavenger of DPPH or ABTS radicals and did not protect against the
      oxidation of Fe(2+). CONCLUSIONS: These results clearly indicated that DHA
      reductase- and GST-like activity are the mechanisms involved in the antioxidant
      effect of (PhSe)(2).

PMID- 20796194
TI  - Novel mucoadhesive polysaccharide isolated from Bletilla striata improves the
      intraocular penetration and efficacy of levofloxacin in the topical treatment of
      experimental bacterial keratitis.
AB  - OBJECTIVES: The objective of the present study was to evaluate a novel
      mucoadhesive polymer extracted from Bletilla striata for ocular delivery of 0.5%
      levofloxacin in rabbits, and to determine its improved efficacy against
      experimental keratitis. METHODS: B. striata polysaccharide (BsP) was subjected to
      cell cytotoxicity and ferning tests. The pharmacokinetics and bioavailability of
      topically applied 0.5% levofloxacin-BsP eye drops was investigated and compared
      with 0.5% levofloxacin eye drops (Cravit). Experimental Staphylococcus aureus
      keratitis was induced and treated with levofloxacin or levofloxacin-BsP eye
      drops. KEY FINDINGS: BsP markedly increased the proliferative capacity of a human
      corneal epithelial [corrected] cell line. The ferning test showed that BsP
      exhibited optimal performance as a tear fluid. The polysaccharides significantly
      increased intra-aqueous penetration and corneal accumulation in rabbits.
      Treatment with levofloxacin-BsP reduced the number of organisms more
      significantly than eye drops containing levofloxacin alone. CONCLUSIONS: BsP
      appears to be a promising candidate as a vehicle for topical ophthalmic drug
      delivery, especially for antibiotics.

PMID- 20796195
TI  - Anti-inflammatory and anticancer compounds isolated from Ventilago madraspatana
      Gaertn., Rubia cordifolia Linn. and Lantana camara Linn.
AB  - OBJECTIVES: The aim was to search for anti-inflammatory and anticancer compounds
      from three medicinal plants, viz. Ventilago madraspatana Gaertn., Rubia
      cordifolia Linn. and Lantana camara Linn. METHODS: The NO* scavenging potential
      of selected plant extracts was determined on LPS/IFN-gamma activated murine
      peritoneal macrophage cultures, and iNOS and COX-2 expression was evaluated by
      Western blot analysis. Bio-assay guided fractionation yielded four compounds:
      physcion and emodin from V. madraspatana, 1-hydroxytectoquinone from R.
      cordifolia, and oleanonic acid from L. camara. The anti-inflammatory activity of
      these compounds was tested through the carrageenan-induced rat-paw oedema model.
      They were then tested against a murine tumour (Ehrlich ascites carcinoma), and
      three human cancer cell lines, namely A375 (malignant skin melanoma), Hep2
      (epidermoid laryngeal carcinoma) and U937 (lymphoma). KEY FINDINGS: All four
      compounds dose dependently inhibited NO* through suppression of iNOS protein
      without affecting macrophage viability. Physcion and emodin caused 65-68%
      reduction of oedema volume at 40 mg/kg, which validated their in-vivo anti
      inflammatory effect. 1-Hydroxytectoquinone and oleanonic acid exhibited promising
      cytotoxicity against A375 cells. CONCLUSIONS: Ethnomedical reports on these
      traditional medicinal plants have been rationalised through an insight into the
      anti-inflammatory as well as anticancer potential of four constituents,
      characterised to be prospective candidates for designing novel therapeutic
      agents.

PMID- 20796196
TI  - Vasorelaxant effect of Valeriana edulis ssp. procera (Valerianaceae) and its mode
      of action as calcium channel blocker.
AB  - OBJECTIVES: The aim was to evaluate the relaxant effect of extracts from
      Valeriana edulis and determine the possible mechanism of action of the hexanic
      extract as vasorelaxant agent. METHODS: Extracts from rhizomes obtained by
      maceration (hexanic (HEVe), dichloromethanic (DEVe), methanolic (MEVe) and
      hydroalcoholic (HAEVe) (3.03-500 microg/ml)) were evaluated on aortic rat rings
      with and without endothelium. KEY FINDINGS: Extracts induced a significant
      concentration-dependent and endothelium-independent relaxation on isolated rat
      aorta pre-contracted with noradrenaline (0.1 microM). HEVe, the most potent
      extract (0.15-50 microg/ml), induced relaxation in aortic rings pre-contracted
      with KCl (80 mM), with an IC50 value of 34.61 +/- 1.41 microg/ml and E(max) value
      of 85.0 +/- 4.38%. Pretreatment with HEVe (30 microg/ml) also inhibited
      contractile responses to noradrenaline and CaCl(2). HEVe (9.98 +/- 2.0 microg/ml)
      reduced noradrenaline-induced transient contraction in Ca(2+)-free solution, and
      inhibited contraction induced by KCl (80 mM). In endothelium-denuded rings, the
      vasorelaxant effect of HEVe was not modified by 1-H-[1,2,4]-oxadiazolo-[4,3a]
      quinoxalin-1-one (1 microM), tetraethylammonium (5 mM), glibenclamide (10 microM)
      or 2-aminopyridine (100 microM). CONCLUSIONS: Our results suggest that HEVe
      induces relaxation through an endothelium-independent pathway, involving blockade
      of Ca(2+) channels, and this effect could be related to the presence of
      valepotriates.

PMID- 20796197
TI  - Bacopa monniera protects rat heart against ischaemia-reperfusion injury: role of
      key apoptotic regulatory proteins and enzymes.
AB  - OBJECTIVES: Rat isolated hearts were perfused in a Langendorff model to study the
      cardioprotective effects of Bacopa monniera, a medicinal herb used in the Indian
      system of medicine, on cardiomyocyte apoptosis and antioxidant status following
      ischaemia-reperfusion (I-R) injury. METHODS: Forty-eight rats were randomly
      divided into four groups (12 in each group): sham group (no ischaemia-reperfusion
      injury), B. monniera control group (orally fed B. monniera at a dose of 75 mg/kg,
      for three weeks); ischaemia-reperfusion control group(subjected to ischaemia
      reperfusion-induced myocardial injury) and B. monniera-treated group (same
      protocol as ischaemia-reperfusion control group except that rats also fed B.
      monniera). KEY FINDINGS: Post-ischaemic reperfusion injury resulted in
      significant cardiac necrosis, apoptosis, depression of heart rate, decline in
      antioxidant status and elevation in lipid peroxidation. Oral administration of B.
      monniera per se for three weeks to healthy rats caused augmentation of myocardial
      antioxidants, superoxide dismutase, catalase and glutathione, along with
      induction of heat shock protein 72 (HSP72). Ischaemia-reperfusion-induced
      biochemical and histopathological perturbations were significantly prevented by
      B. monniera (75 mg/kg) pre-treatment. Interestingly, B. monniera also restored
      the antioxidant network of the myocardium and reduced myocardial apoptosis,
      caspase 3 and Bax protein expression. CONCLUSIONS: Histopathological studies and
      myocardial creatine phosphokinase content further confirmed the cardioprotective
      effects of B. monniera (75 mg/kg) in the experimental model of ischaemia
      reperfusion injury. The study provides scientific basis for the putative
      therapeutic effect of B. monniera in ischaemic heart disease.

PMID- 20796198
TI  - Difference in blood tacrolimus concentration between ACMIA and MEIA in samples
      with low haematocrit values.
AB  - OBJECTIVES: The aim was to compare blood tacrolimus concentrations in anaemic
      patients between affinity column-mediated immunoassay (ACMIA) and microparticle
      enzyme immunoassay (MEIA). METHODS: Blood concentrations of tacrolimus in 235
      whole-blood samples from 64 patients treated with tacrolimus were determined by
      the two assay methods. Fifty-three samples had low haematocrit (Ht) values
      (<25%), whereas the other samples had normal Ht values. KEY FINDINGS: Measured
      tacrolimus concentrations in samples with normal Ht values did not differ between
      ACMIA and MEIA (median, range; 6.6, 0-29.1 vs 7.3, 0-27.4 ng/ml). On the other
      hand, MEIA determined significantly higher tacrolimus concentrations in samples
      with lower Ht values compared with ACMIA (14.0, 2.4-25.7 vs 11.5, 0-21.3 ng/ml; P
      < 0.05). This difference was caused by overestimated blood concentrations in MEIA
      derived from lower Ht values, which could be corrected using the Ht value for
      each sample (calculated MEIA (MEIAcalc)). The corrected concentrations (MEIAcalc;
      10.8, 0-21.3 ng/ml) were comparable with those of ACMIA. It was confirmed that
      the difference in concentrations between ACMIA and MEIA was remarkable in routine
      monitoring of blood tacrolimus for a liver transplant recipient with anaemia.
      CONCLUSIONS: ACMIA can be applied to routine therapeutic drug monitoring of
      tacrolimus therapy in anaemic patients.

PMID- 20796199
TI  - In-vitro permeation of bevacizumab through human sclera: effect of iontophoresis
      application.
AB  - OBJECTIVES: Bevacizumab (Avastin) is a recombinant humanized monoclonal antibody
      used in ophthalmology (off-label) for the treatment of neovascularization in
      diseases such as diabetic retinopathy and age-related macular degeneration (wet
      form). Bevacizumab is currently administrated by repeated intravitreal injection,
      which can cause severe complications; a non-invasive delivery route is therefore
      desirable. The passive permeation of bevacizumab through isolated human sclera
      was evaluated and the iontophoretic technique was explored as a method to enhance
      its transscleral transport in vitro. METHODS: Bevacizumab was fluorescently
      labelled using fluorescein isothiocyanate (FITC). Permeation experiments were
      conducted for 2 h in Franz-type diffusion cells using human sclera as the
      barrier. The donor compartment contained FITC-bevacizumab (2.5 mg/ml) in
      phosphate-buffered saline at pH 7.4. In the iontophoretic experiments, a current
      intensity of 2.3 mA (current density 3.8 mA/cm(2)) was applied. The permeation
      samples were analysed with a fluorescence detector (excitation and emission
      wavelengths were 490 and 520 nm, respectively). The stability of FITC-bevacizumab
      conjugate was checked by thin layer chromatography. KEY FINDINGS: The main
      finding of this work is that anodal iontophoresis can significantly enhance
      bevacizumab transport through isolated human sclera (enhancement factor 7.5),
      even though the drug is essentially uncharged. Due to the relatively constant
      characteristics of antibodies, these results can probably be extended to other
      molecules of the same family. CONCLUSIONS: Preliminary results indicate that
      anodal iontophoresis could be a promising strategy to non-invasively deliver
      bevacizumab through the sclera. The presence in the eye of other barriers, both
      static and dynamic, necessitates further evaluation of the technique on more
      complex ex-vivo and in-vivo models.

PMID- 20796200
TI  - Towards the development of a rapid, portable, surface enhanced Raman spectroscopy
      based cleaning verification system for the drug nelarabine.
AB  - OBJECTIVES: Cleaning verification is a scientific and economic problem for the
      pharmaceutical industry. A large amount of potential manufacturing time is lost
      to the process of cleaning verification. This involves the analysis of residues
      on spoiled manufacturing equipment, with high-performance liquid chromatography
      (HPLC) being the predominantly employed analytical technique. The aim of this
      study was to develop a portable cleaning verification system for nelarabine using
      surface enhanced Raman spectroscopy (SERS). METHODS: SERS was conducted using a
      portable Raman spectrometer and a commercially available SERS substrate to
      develop a rapid and portable cleaning verification system for nelarabine. Samples
      of standard solutions and swab extracts were deposited onto the SERS active
      surfaces, allowed to dry and then subjected to spectroscopic analysis. KEY
      FINDINGS: Nelarabine was amenable to analysis by SERS and the necessary levels of
      sensitivity were achievable. It is possible to use this technology for a semi
      quantitative limits test. Replicate precision, however, was poor due to the
      heterogeneous drying pattern of nelarabine on the SERS active surface.
      Understanding and improving the drying process in order to produce a consistent
      SERS signal for quantitative analysis is desirable. CONCLUSIONS: This work shows
      the potential application of SERS for cleaning verification analysis. SERS may
      not replace HPLC as the definitive analytical technique, but it could be used in
      conjunction with HPLC so that swabbing is only carried out once the portable SERS
      equipment has demonstrated that the manufacturing equipment is below the
      threshold contamination level.

PMID- 20796201
TI  - Penile enhancement using autologous tissue engineering with biodegradable
      scaffold: a clinical and histomorphometric study.
AB  - INTRODUCTION: Autologous tissue engineering with biodegradable scaffolds is a new
      treatment option for real penile girth enhancement. AIM: The aim of this article
      is to evaluate tissue remodeling after penile girth enhancement using this
      technique. METHODS: Between June 2005 and May 2007, a group of 12 patients
      underwent repeated penile widening using biodegradable scaffolds enriched with
      expanded autologous scrotal dartos cells. Clinical monitoring was parallel to
      histological investigation of tissue remodeling. During second surgical
      procedure, biopsies were obtained 10-14 months after first surgery (mean 12
      months, N=6) and compared with those obtained after 22-24 months (mean 23 months,
      N=6), and control biopsies from patients who underwent circumcision (N=5). Blind
      evaluation of histomorphometrical and immunohistochemical finding was performed
      in paraffin sections. MAIN OUTCOME MEASUREMENTS: Penile girth gain in a flaccid
      state ranged between 1.5 and 3.8 cm (mean 2.1 +/- 0.28 cm) and in full erection
      between 1.2 and 4 cm (mean 1.9 +/- 0.28 cm). Patients' satisfaction, defined by a
      questionnaire, was good (25%) and very good (75%). RESULTS: In biopsies obtained
      10-14 months after first surgery, highly vascularized loose tissue with collagen
      deposition associated with small foci of mild chronic and granulomatous
      inflammation surrounding residual amorphous material was observed. Fibroblast
      like hyperplasia and small vessel neoangiogenesis occurred intimately associated
      with the progressive growth of vascular-like structures from accumulation of CD34
      and alpha-smooth muscle actin-positive cells surrounding residual scaffold-like
      amorphous material. Capillary neoangiogenesis occurred inside residual amorphous
      material. In biopsies obtained after 22-24 months, inflammation almost
      disappeared and tissue closely resembled that of the dartos fascia of control
      group. CONCLUSIONS: Autologous tissue engineering using expanded scrotal dartos
      cells with biodegradable scaffolds is a new and promising method for penile
      widening that generates progressive accumulation of stable collagen-rich, highly
      vascularized tissue matrix that closely resemble deep dartos fascia.

PMID- 20796204
TI  - Can we predict indirect interactions from quantitative food webs?--an
      experimental approach.
AB  - 1. Shared enemies may link the dynamics of their prey. Recently, quantitative
      food webs have been used to infer that herbivorous insect species attacked by the
      same major parasitoid species will affect each other negatively through apparent
      competition. Nonetheless, theoretical work predicts several alternative outcomes,
      including positive effects. 2. In this paper, we use an experimental approach to
      link food web patterns to realized population dynamics. First, we construct a
      quantitative food web for three dominant leaf miner species on the oak Quercus
      robur. We then measure short- and long-term indirect effects by increasing leaf
      miner densities on individual trees. Finally, we test whether experimental
      results are consistent with natural leaf miner dynamics on unmanipulated trees.
      3. The quantitative food web shows that all leaf miner species share a minimum of
      four parasitoid species. While only a small fraction of the parasitoid pool is
      shared among Tischeria ekebladella and each of two Phyllonorycter species, the
      parasitoid communities of the congeneric Phyllonorycter species overlap
      substantially. 4. Based on the structure of the food web, we predict strong short
      and long-term indirect interactions between the Phyllonorycter species, and
      limited interactions between them and T. ekebladella. As T. ekebladella is the
      main source of its own parasitoids, we expect to find intraspecific density
      dependent parasitism in this species. 5. Consistent with these predictions,
      parasitism in T. ekebladella was high on trees with high densities of
      conspecifics in the previous generation. Among leaf miner species sharing more
      parasitoids, we found positive rather than negative interactions among years. No
      short-term indirect interactions (i.e. indirect interactions within a single
      generation) were detected. 6. Overall, this study is the first to experimentally
      demonstrate that herbivores with overlapping parasitoid communities may exhibit
      independent population dynamics - or even apparent mutualism. Hence, it proves
      the potential for versatile indirect interactions in nature, and suggests that
      the link between patterns in food web structure and realized population dynamics
      should be verified by rigorous experiments.

PMID- 20796202
TI  - Laminin promotes coagulation and thrombus formation in a factor XII-dependent
      manner.
AB  - BACKGROUND: Laminin is the most abundant non-collagenous protein in the basement
      membrane. Recent studies have shown that laminin supports platelet adhesion,
      activation and aggregation under flow conditions, highlighting a possible role
      for laminin in hemostasis. OBJECTIVE: To investigate the ability of laminin to
      promote coagulation and support thrombus formation under shear. RESULTS AND
      METHODS: Soluble laminin accelerated factor (F) XII activation in a purified
      system, and shortened the clotting time of recalcified plasma in a FXI- and FXII
      dependent manner. Laminin promoted phosphatidylserine exposure on platelets and
      supported platelet adhesion and fibrin formation in recalcified blood under shear
      flow conditions. Fibrin formation in laminin-coated capillaries was abrogated by
      an antibody that interferes with FXI activation by activated FXII, or an antibody
      that blocks activated FXI activation of FIX. CONCLUSION: This study identifies a
      role for laminin in the initiation of coagulation and the formation of platelet
      rich thrombi under shear conditions in a FXII-dependent manner.

PMID- 20796205
TI  - Analysis of spatial niche structure in coexisting tidepool fishes: null models
      based on multi-scale experiments.
AB  - 1. Fundamental and realized spatial niches were investigated through a
      combination of laboratory and mesocosm experiments, field observations and null
      model analysis in three intertidal gobiid species (Bathygobius fuscus,
      Chaenogobius annularis and C. gulosus). Null models based on the results of
      single-species experiments were used to assess interspecific spatial use and
      coexistence on two different scales: (i) microhabitats within a tidepool
      ('microhabitat' scale); and (ii) distribution among a set of tidepools ('habitat
      wide' scale). 2. Patterns of microhabitat use varied from single to paired
      treatments, depending on paired species. Realized overlap of microhabitat use was
      smaller than would be expected from single-individual situations for
      intraspecific combinations, but not for interspecific ones. 3. Patterns of
      tidepool occupancy (a measure of spatial niche breadth) in the mesocosm were
      influenced by interspecific interactions. Two Chaenogobius species, but not B.
      fuscus, decreased tidepool occupancy in the hetero-specific treatments compared
      with the mono-specific ones. For all interspecific combinations, spatial overlap
      (habitat-wide scale) was significantly lower than the values expected from mono
      specific situations. The results also indicated a possible trade-off between
      competitiveness and growth efficiency in these fishes. 4. Interspecific spatial
      overlap in the field was similar to that in the mesocosm experiment and the
      pattern of coexistence of gobiids can be explained by the results of our
      experiments. 5. This study demonstrates that niches of intertidal fishes may
      experience modifications under the influence of species interactions and that
      null models based on controlled experiments can greatly facilitate the
      deciphering of such changes in niche structure.

PMID- 20796206
TI  - Linking disease and community ecology through behavioural indicators:
      immunochallenge of white-footed mice and its ecological impacts.
AB  - 1. Pathogens and immune challenges can induce changes in host phenotype in ways
      that indirectly impact important community interactions, including those that
      affect host-pathogen interactions. 2. To explore host behavioural response to
      immune challenge, we exposed wild white-footed mice (Peromyscus leucopus) to an
      immunogen from an endemic, zoonotic pathogen, the spirochete Borrelia
      burgdorferi. White-footed mice are a major reservoir host of Lyme disease (LD)
      spirochetes in northeastern USA and an abundant member of forest communities. The
      activity patterns, foraging behaviour, and space use of white-footed mice have
      implications for population growth rates of community members upon which mice
      incidentally prey (i.e. gypsy moths and native thrushes), as well as potentially
      determining host-vector encounter rates and human risk of LD. 3. Immunochallenge
      led to specific humoral (antibody) and cellular (i.e. elevated neutrophils and
      eosinophils) immune responses, supporting use of the immunogen as a surrogate for
      pathogenic infection. 4. Immunochallenged mice had reduced wheel-running activity
      early in the night when measured in the lab. However, mouse activity, as measured
      by track plates in natural field experiments, did not differ between mice exposed
      to the immunogen and unexposed mice. 5. Foraging behaviour of wild mice in the
      field - assessed with giving-up densities of seed at artificial feeding stations 
      was affected by exposure to the immunogen. Whereas immunochallenge did not
      influence whether foraging mice gained information on patch quality while
      foraging, it led to reductions in predator avoidance during foraging, suggesting
      that the proportion of space used by foraging mice may be greater as a result of
      immunochallenge. This increased space use is predicted to increase encounter
      rates with patchily distributed LD vectors (ticks) and with incidental prey
      items. 6. Thus, immunochallenge in white-footed mice, and potentially pathogenic
      infection, have the potential to indirectly impact community interactions,
      including those important for pathogen transmission.

PMID- 20796207
TI  - Epidemiology of thrombocytopenia in patients with chronic hepatitis C: more than
      meets the eye.
AB  - Thrombocytopenia is likely the most common haematological abnormality that can be
      diagnosed inpatients affected by chronic liver disease. In these patients,the
      presence of thrombocytopenia may have significant clinical implications. In fact,
      it can be a limiting factor when considering invasive procedures and may hamper
      the out come of antiviral therapy with interferon. The prevalence of decreased
      platelet count in patients with chronic hepatitis Chas been assessed in various
      studies that evaluated heterogenous patient populations and used various platelet
      count threshold to identify thrombocytopenia. This review shows that the
      prevalence of thrombocytopenia in these patients is variable and mainly depends
      upon the severity of the underlying liver disease and the criterion used to
      identify this haematological abnormality. Furthermore, the results of this
      epidemiological review provide an indirect evidence that confirms the
      multiplicity of aetiological factors underlying the pathophysiology of
      thrombocytopenia in chronic hepatitis C patients. Lastly, this study shows that
      up to 25% of patients treated with interferon may develop some degree of
      thrombocytopenia, and this may be associated with decreased sustained virological
      response rates.

PMID- 20796208
TI  - Prevalence of thrombocytopenia among patients with chronic hepatitis C: a
      systematic review.
AB  - Thrombocytopenia (TCP) is a haematological condition known to occur in
      chronically infected hepatitis C (HCV) patients and may interfere with diagnostic
      procedures, such as liver biopsy, because of risk of bleeding. It may also
      exclude patients from effective antiviral treatment. We conducted a systematic
      literature review of articles and conference abstracts, to assess the prevalence
      of TCP among those with HCV and to describe demographics, liver disease stage and
      treatment characteristics of these patients. Studies of individuals with
      confirmed chronic HCV infection were included in the review if the study had a
      clear definition of thrombocytopenia and a sample size of at least 50 subjects.
      The final selection included 27 studies (21 articles and six abstracts). The
      definitions of thrombocytopenia varied between studies and were based either on
      platelet counts, with threshold levels ranging between <= 100 * 10(9) and <= 180
      * 10(9) /L, or on criteria set in haematological guidelines. The prevalence of
      TCP ranged from 0.16% to 45.4% and more than half of the studies reported a TCP
      prevalence of 24% or more. Because of the different TCP definitions,
      heterogeneity in study design and insufficient data on study characteristics such
      as age, gender, HCV treatment rates and disease severity an overall summary
      estimate of TCP prevalence among patients with HCV was not feasible. However, the
      relatively large prevalence in the majority of the studies suggests that there
      may be a substantial number of HCV patients at risk of bleeding complications and
      reduced likelihood of successful HCV antiviral treatment.

PMID- 20796209
TI  - Bacteriophage applications: where are we now?
AB  - Bacteriophages are bacterial viruses and have been used for almost a century as
      antimicrobial agents. In the West, their use diminished when chemical antibiotics
      were introduced, but they remain a common therapeutic approach in parts of
      eastern Europe. Increasing antibiotic resistance in bacteria has driven the
      demand for novel therapies to control infections and led to the replacement of
      antibiotics in animal husbandry. Alongside this, increased pressure to improve
      food safety has created a need for faster detection of pathogenic bacteria.
      Hence, there has been a resurgence of interest in bacteriophage applications, and
      this has encouraged the emergence of a large number of biotech companies hoping
      to commercialize their use. Research in Europe and the United States has
      increased steadily, leading to the development of a range of applications for
      bacteriophage agents for the healthcare, veterinary and agricultural sectors.
      This article will attempt to answer the question of whether bacteriophages are
      now delivering on their potential.

PMID- 20796210
TI  - Presence of sourdough lactic acid bacteria in commercial total mixed ration
      silage as revealed by denaturing gradient gel electrophoresis analysis.
AB  - AIMS: To characterize the bacterial communities in commercial total mixed ration
      (TMR) silage, which is known to have a long bunk life after silo opening. METHODS
      AND RESULTS: Samples were collected from four factories that produce TMR silage
      according to their own recipes. Three factories were sampled three times at 1
      month intervals during the summer to characterize the differences between
      factories; one factory was sampled 12 times, three samples each during the
      summer, autumn, winter and spring, to determine seasonal changes. Bacterial
      communities were determined by culture-independent denaturing gradient gel
      electrophoresis. All silages contained lactic acid as the predominant acid, and
      the contents appeared stable regardless of factories and product seasons. Acetic
      acid and 1-propanol contents were different between factories and indicated
      seasonal changes, with increases in warm seasons compared to cool seasons. Both
      differences and similarities existed among the bacterial communities from each
      factory and product season. Lactobacillus parabuchneri was found in the products
      from three of four factories. Various sourdough lactic acid bacteria (LAB) were
      identified in commercial TMR silage; Lactobacillus panis, Lactobacillus hammesii,
      Lactobacillus mindensis, Lactobacillus pontis, Lactobacillus frumenti and
      Lactobacillus farciminis were detected in many products. Moreover, changes owing
      to product season were distinctive, and Lact. pontis and Lact. frumenti became
      detectable in summer products. CONCLUSION: Sourdough LAB are involved in the
      ensiling of commercial TMR silage. Silage bacterial communities vary more by
      season than by factory. The LAB species Lact. parabuchneri was detected in the
      TMR silage but may not be essential to the product's long bunk life after silo
      opening. SIGNIFICANCE AND IMPACT OF THE STUDY: Commercial TMR silage resembles
      sourdough with respect to bacterial communities and long shelf life. The roles of
      sourdough LAB in the ensiling process and aerobic stability are worth examining.

PMID- 20796211
TI  - Surfactin: a novel mosquitocidal biosurfactant produced by Bacillus subtilis ssp.
      subtilis (VCRC B471) and influence of abiotic factors on its pupicidal efficacy.
AB  - AIM: The rpoB gene of the mosquito pupicidal isolate Bacillus subtilis (VCRC
      B471) was amplified to confirm the subspecies as subtilis. The mosquito pupicidal
      activity expressed by the biosurfactant surfactin is novel, and hence, the
      influence of abiotic factors like pH, temperature of water and sunlight on its
      efficacy was studied under laboratory conditions. METHODS AND RESULTS: The rpoB
      gene amplicon of the bacterium (c. 570 bp of) was sequenced (accession number:
      EU057603). The relatedness of the bacterium to other members of the genus
      Bacillus was studied by tree construction, and the identity of VCRC B471 was
      confirmed as B. subtilis ssp. subtilis. The mosquito pupicidal activity exhibited
      by surfactin was found to be unaffected between pH 3-9, temperatures 25 and 37 
      degrees C and exposure to sunlight/UV radiation. Further, the pupicidal activity
      of surfactin was not diminished after exposure to 121  degrees C for 15 min,
      indicating its thermostable nature. CONCLUSIONS: VCRC B471 is confirmed as a
      strain of B. subtilis ssp. subtilis. The mosquitocidal toxin, surfactin produced
      by this bacterium being stable to UV and varied temperature, active at acidic and
      basic pH and temperatures between 25 and 42  degrees C renders this molecule an
      interesting lead to be developed as a mosquitocidal agent. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The mosquitocidal toxin, surfactin produced by B. subtilis
      ssp. subtilis (VCRC B471), being a biodegradable biosurfactant, exhibiting high
      stability to varied environmental conditions, can be used year round in breeding
      habitats and will be a prospective microbial toxin for use against mosquitoes.

PMID- 20796212
TI  - Inter-laboratory validation of a rapid assay for the detection and quantification
      of Legionella spp. in water samples.
AB  - AIMS: To compare the standard culture method with a new, rapid test (ScanVIT
      LegionellaTM) using fluorescently labelled gene probes for the detection and
      enumeration of Legionella spp. The new technique was validated through
      experiments conducted on both artificially and naturally contaminated water and
      through an inter-laboratory comparison. METHODS AND RESULTS: All samples were
      processed by the ScanVIT test according to the manufacturer's instructions and by
      a culture method (ISO 11731). ScanVIT detected significantly more positive
      samples, although concentrations were similar and a strong positive correlation
      between the two methods was observed (r = 0.888, P < 0.001). The new test was
      more accurate in identifying the co-presence of Legionella pneumophila and Leg.
      non-pneumophila. ScanVIT showed a slightly higher Legionella recovery from water
      samples artificially contaminated with Leg. pneumophila alone or together with
      Pseudomonas aeruginosa. Lastly, the inter-laboratory comparison revealed that the
      ScanVIT test exhibits a lower variability than the traditional culture test (mean
      coefficient of variation 8.7 vs 16.1%). CONCLUSIONS:   The results confirmed that
      the ScanVIT largely overlaps the reference method and offers advantages in terms
      of sensitivity, quantitative reliability and reduced assay time. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The proposed method may represent a useful validated
      alternative to traditional culture for the rapid detection and quantification of
      Legionella spp. in water.

PMID- 20796213
TI  - Function and morphology correlates of rectal nerve mechanoreceptors innervating
      the guinea pig internal anal sphincter.
AB  - BACKGROUND: Mechanoreceptors to the internal anal sphincter (IAS) contribute to
      continence and normal defecation, yet relatively little is known about their
      function or morphology. We investigated the function and structure of
      mechanoreceptors to the guinea pig IAS. METHODS: Extracellular recordings from
      rectal nerve branches to the IAS in vitro, combined with anterograde labeling of
      recorded nerve trunks, were used to characterize extrinsic afferent nerve endings
      activated by circumferential distension. KEY RESULTS: Slowly adapting, stretch
      sensitive afferents were recorded in rectal nerves to the IAS. Ten of 11 were
      silent under basal conditions and responded to circumferential stretch in a
      saturating linear manner. Rectal nerve afferents responded to compression with
      von Frey hairs with low thresholds (0.3-0.5 mN) and 3.4 +/- 0.5 discrete,
      elongated mechanosensitive fields of innervation aligned parallel to circular
      muscle bundles (length = 62 +/- 16 mm, n = 10). Anterogradely labeled rectal
      nerve axons typically passed through sparse irregular myenteric ganglia adjacent
      to the IAS, before ending in extensive varicose arrays within the circular muscle
      and, to a lesser extent, the longitudinal muscle overlying the IAS. Few (8%) IAS
      myenteric ganglia contained intraganglionic laminar endings. In eight
      preparations, mechanotransduction sites were mapped in combination with
      successful anterograde fills. Mechanotransduction sites were strongly associated
      with extensive fine varicose arrays within the circular muscle (P < 0.05), and
      not with any other neural structures. CONCLUSIONS & INFERENCES:
      Mechanotransduction sites for low-threshold, slowly adapting mechanoreceptors
      innervating the IAS are likely to correspond to extensive fine varicose arrays
      within the circular muscle.

PMID- 20796214
TI  - Deficiency in plastidic glutamine synthetase alters proline metabolism and
      transcriptomic response in Lotus japonicus under drought stress.
AB  - The role of plastidic glutamine synthetase (GS2) in proline biosynthesis and
      drought stress responses in Lotus japonicus was investigated using the GS2
      mutant, Ljgln2-2. Wild-type (WT) and mutant plants were submitted to different
      lengths of time of water and nutrient solution deprivation. Several biochemical
      markers were measured and the transcriptional response to drought was determined
      by both quantitative real-time polymerase chain reaction and transcriptomics. The
      Ljgln2-2 mutant exhibited normal sensitivity to mild water deprivation, but
      physiological, biochemical and massive transcriptional differences were detected
      in the mutant, which compromised recovery (rehydration) following re-watering
      after severe drought stress. Proline accumulation during drought was
      substantially lower in mutant than in WT plants, and significant differences in
      the pattern of expression of the genes involved in proline metabolism were
      observed. Transcriptomic analysis revealed that about three times as many genes
      were regulated in response to drought in Ljgln2-2 plants compared with WT. The
      transcriptomic and accompanying biochemical data indicate that the Ljgln2-2
      mutant is subject to more intense cellular stress than WT during drought. The
      results presented here implicate plastidic GS2 in proline production during
      stress and provide interesting insights into the function of proline in response
      to drought.

PMID- 20796215
TI  - Phosphatidic acid mediates salt stress response by regulation of MPK6 in
      Arabidopsis thaliana.
AB  - * Phospholipase D (PLD) hydrolyzes phospholipids to produce phosphatidic acid
      (PA) and a head group, and is involved in the response to various environmental
      stresses, including salinity. Here, we determined the roles of PLDalpha and PA in
      the mediation of salt (NaCl)-stress signaling through the regulation of mitogen
      activated protein kinase (MAPK or MPK) in Arabidopsis thaliana. * NaCl-induced
      changes in the content and composition of PA were quantitatively profiled by
      electrospray ionization-tandem mass spectrometry (ESI-MS/MS). A specific PA
      species (a MAPK 16:0-18:2 PA), which was increased in abundance by exposure to
      NaCl, bound to a MPK6, according to filter binding and ELISA. The effect of PA on
      MPK6 activity was tested using in-gel analysis. * 16:0-18:2 PA stimulated the
      activity of MPK6 immunoprecipitated from Arabidopsis leaf extracts. Treatment
      with NaCl induced a transient activation of MPK6 in wild-type plant, but the
      activation was abolished in the pldalpha1 plant mutant. A plasma membrane
      Na(+)/H(+) antiporter (SOS1) was identified as a downstream target of MPK6. MPK6
      phosphorylated the C-terminal fragment of SOS1. The MPK6 phosphorylation of SOS1
      was stimulated by treatment with NaCl, as well as directly by PA. * These results
      suggest that PA plays a critical role in coupling MAPK cascades in response to
      salt stress.

PMID- 20796216
TI  - Impact of water intake on energy intake and weight status: a systematic review.
AB  - The effects of consuming water with meals rather than drinking no beverage or
      various other beverages remain under-studied. This systematic review of studies
      reported in the English-language literature was performed to compare the effects
      of drinking water and various beverage alternatives on energy intake and/or
      weight status. Relevant clinical trials, epidemiologic studies, and intervention
      studies were identified and findings across the literature were summarized. From
      the clinical trials, average differences were calculated in total energy intake
      at test meals (DeltaTEI) for each of several beverage categories in comparison
      with water. The available literature for these comparisons is sparse and somewhat
      inconclusive. However, one of the most consistent sets of findings was related to
      adults drinking sugar-sweetened beverages (SSBs) versus water before a single
      meal. In these comparisons, total energy intakes were 7.8% higher (DeltaTEI
      range, -7.5 to 18.9) when SSBs were consumed. Studies comparing non-nutritive
      sweeteners with water were also relatively consistent and found no impact on
      energy intake among adults (DeltaTEI, -1.3; range, -9 to 13.8). Much less
      conclusive evidence was found in studies replacing water with milk and juice,
      with estimated increases in TEI of 14.9% (range, 10.9 to 23.9%). These findings
      from clinical trials, along with those from epidemiologic and intervention
      studies, suggest water has a potentially important role to play in reducing
      energy intake, and consequently in obesity prevention. A need for randomized
      controlled trials to confirm this role exists.

PMID- 20796217
TI  - Use of ferrous fumarate to fortify foods for infants and young children.
AB  - Ferrous fumarate is currently recommended for use in the fortification of foods
      for infants and young children. This recommendation is based on the compound's
      good sensory properties and on results from isotope studies in adults that
      reported similar iron absorption values for ferrous fumarate and ferrous sulphate
      (relative bioavailability [RBV] of ferrous fumarate, 100). However, later isotope
      studies conducted on both iron-replete and iron-deficient young children found
      that iron absorption from ferrous fumarate was only about 30% of that achieved
      from ferrous sulphate (RBV, 30). The reasons for the differences observed in
      adults compared with children are unclear but could be related to the following
      factors: lower iron status in children resulting in greater iron absorption via
      upregulation from ferrous sulphate but not from ferrous fumarate; reduced gastric
      acid secretion in children leading to retarded dissolution of ferrous fumarate;
      or an influence of added ascorbic acid on RBV. Ferrous fumarate-fortified
      complementary foods have been demonstrated to improve iron status in iron
      deficient infants and, more recently, to prevent iron deficiency equally as well
      as ferrous sulphate in iron-replete infants. However, current evidence indicates
      that iron-deficient infants and young children may absorb iron from ferrous
      fumarate less well than iron from ferrous sulfate and that, for equivalent
      efficacy, complementary foods targeted at such infants and young children should
      contain more iron in the form of fumarate.

PMID- 20796219
TI  - Clinical pharmacology of isoflavones and its relevance for potential prevention
      of prostate cancer.
AB  - Isoflavones are phytoestrogens that have pleiotropic effects in a wide variety of
      cancer cell lines. Many of these biological effects involve key components of
      signal transduction pathways within cancer cells, including prostate cancer
      cells. Epidemiological studies have raised the hypothesis that isoflavones may
      play an important role in the prevention and modulation of prostate cancer
      growth. Since randomized phase III trials of isoflavones in prostate cancer
      prevention are currently lacking, the best evidence for this concept is presently
      provided by case control studies. However, in vitro data are much more convincing
      in regard to the activity of a number of isoflavones, and have led to the
      development of genistein and phenoxodiol in the clinic as potential treatments
      for cancer. In addition, the potential activity of isoflavones in combination
      with cytotoxics or radiotherapy warrants further investigation. This review
      focuses on the clinical pharmacology of isoflavones and its relevance to their
      development for use in the prevention of prostate cancer, and it evaluates some
      of the conflicting data in the literature.

PMID- 20796220
TI  - Health nutrition practice in Italy.
AB  - The increasing need for nutrition professionals is driven by growing public
      interest in nutrition and the potential of nutrition to prevent and treat a
      variety of diet-related conditions. Health promotion units and health services
      face great challenges in trying to address current and future population health
      issues. This review describes the present state of health nutrition practice in
      Italy, exploring the nature, role, and utility of training for nutrition
      professionals to meet the increasing burden of nutrition-related diseases.
      Evidence suggests that the public health nutrition workforce and infrastructures
      lack the necessary capacity to respond to national population needs regarding
      food and nutrition at many levels. This situation is aggravated by the growing
      prevalence of nutrition-related diseases as well as by the lack of adequate
      academic nutrition training. The public health nutrition infrastructures need to
      be enhanced, as do the education and training systems. Roles and functions in
      health nutrition practice need to be defined and discipline-specific competencies
      should be integrated.

PMID- 20796218
TI  - Omega-3 fatty acids in critical illness.
AB  - Supplementation of enteral nutritional formulas and parenteral nutrition lipid
      emulsions with omega-3 fatty acids is a recent area of research in patients with
      critical illness. It is hypothesized that omega-3 fatty acids may help reduce
      inflammation in critically ill patients, particularly those with sepsis and acute
      lung injury. The objective of this article is to review the data on supplementing
      omega-3 fatty acids during critical illness; enteral and parenteral supplemental
      nutrition are reviewed separately. The results of the research available to date
      are contradictory for both enteral and parenteral omega-3 fatty acid
      administration. Supplementation with omega-3 fatty acids may influence the acute
      inflammatory response in critically ill patients, but more research is needed
      before definitive recommendations about the routine use of omega-3 fatty acids in
      caring for critically ill patients can be made.

PMID- 20796222
TI  - Low-dose eicosapentaenoic acid and/or docosahexaenoic acid and triglyceride
      lowering.

PMID- 20796224
TI  - Increased expression of peroxiredoxin 6 and cyclophilin A in squamous cell
      carcinoma of the tongue.
AB  - OBJECTIVES: The aim of this study was to assess the expression levels of two
      proteins, such as PRDX6 and cyclophilin A (CypA), and to evaluate their
      relationship with clinicopathologic features and survival in tongue squamous cell
      carcinomas (TSCCs). MATERIAL AND METHODS: An immunohistochemical study was
      performed comprising a total of 42 tissue samples of patients suffering from
      TSCCs as well as 10 corresponding adjacent normal tissues. After detection of
      PRDX6 and CypA, their expression levels were semiquantitatively evaluated and
      correlated with clinicopathologic variables. RESULTS:   Both PRDX6 and CypA
      expressions were significantly higher in tissue samples of TSCCs compared with
      the 10 corresponding adjacent normal tissues (P < 0.01). A statistically
      significant correlation in TSCCs regarding the expression of PRDX6 and CypA was
      revealed (P = 0.005), and the lymphadenectasis was correlated with PRDX6 (P <
      0.05). Results of a multivariate analysis revealed age, CypA expression, cervical
      lymph node metastases, and tongue cancer differentiation to be independent
      prognostic variables in respect of the overall survival rate (P < 0.05).
      CONCLUSIONS: It could be detected that PRDX6 and CypA are associated with
      tumorigenesis in TSCCs. High levels of CypA expression may predict reduced
      survival time.

PMID- 20796225
TI  - Isolated soft tissue cleft lip: epidemiology and associated dental anomalies.
AB  - OBJECTIVES: The aim of this investigation was to study the epidemiology of the
      isolated soft tissue cleft lip (ICL) population and to evaluate the dental
      anomalies associated with permanent dentition. METHODS: The study included 19
      children aged 9-13 years presenting ICL selected from 657 cleft lip-affected
      patients treated during the last 10 years in two craniofacial centers. Only 17
      patients could be included for dental anomaly evaluation: Hyperdontia,
      Hypodontia, Gemination, Talon tooth, Microdontia, and Macrodontia. These were
      compared with cleft lip and palate (CLP) and cleft lip and alveolus (CLA)
      affected populations and with normal populations. RESULTS:  The prevalence of ICL
      was 2.8%. All types of tooth abnormalities were found to be higher and mainly
      significant for the cleft side of ICL compared with the normal population. On the
      side opposite the cleft, the prevalence of dental anomalies reduced toward the
      normal individuals and was not significantly different. The significant
      differences found between CLP, CLA, and ICL-affected populations were mostly
      depicted by lateral incisors and second pre-molar hypodontia. CONCLUSIONS:
      Isolated cleft lip is a rare phenomenon among the spectrum of the cleft-affected
      population. The prevalence of the dental anomalies in ICL maintains the
      proportional trend according to clefting severity.

PMID- 20796226
TI  - Responses of periodontal ligament stem cells on various titanium surfaces.
AB  - OBJECTIVE: Periodontal ligament has been reported to have adult stem cells
      (PDLSCs) which are responsible to regenerate the alveolar bone tissue after tooth
      is removed from its socket. Also PDLSCs may be the stem cells responsible for the
      osseointegration of titanium implants after installing the implant immediately in
      the fresh extracted socket. Here we tested cellular responses of PDLSCs on the
      various titanium surfaces to verify this notion. MATERIALS AND METHODS: Titanium
      disc were prepared for the different surface textures; smooth machined, blasted
      with 75 and 125 MUm Al(2) O(3) particles, and anodized. PDLSCs were cultured on
      these titanium discs and tested their proliferation and gene expressions of
      osteocalcin, osteopontin, type I collagen, and GAPDH. RESULTS:   Proliferation of
      PDLSCs was higher on the rough surface blasted with 75 MUm Al(2) O(3) particles.
      Osteocalcin expression was increased on the Al(2) O(3) particle treated-surface
      regardless of its particle size. Type I collagen expression was generally
      decreased with time in 6 days culture. CONCLUSIONS: In this experiment, it was
      shown that cultured PDLSCs proliferate in higher rate on the rough surface
      especially at the 75 MUm Al(2) O(3) particle treated surface than other surfaces.
      Also, osteocalcin was highly expressed on the rough surfaces treated with 75 MUm
      and 125 MUm Al(2) O(3) particles.

PMID- 20796227
TI  - Reduced statherin reactivity of human submandibular gland in diabetes.
AB  - BACKGROUND AND OBJECTIVES:  Statherin is a salivary protein involved in the
      formation of enamel pellicle and in regulation of calcium homeostasis. Diabetes
      and other pathologies affect both salivary flow and protein secretion by salivary
      glands, causing increased susceptibility to mucosal infections, tooth
      demineralization, and caries. The purpose of this study was to compare the
      statherin expression in submandibular glands of healthy and diabetic subjects.
      MATERIALS AND METHODS:  Fragments of submandibular glands obtained from diabetic
      and non diabetic patients were fixed, dehydrated, embedded in Epon Resin and
      processed for the immunogold histochemistry. The results were statistically
      evaluated. RESULTS:  Specific statherin labeling was demonstrated in secretory
      granules of acinar cells in both diabetic and normal samples. The staining was
      much more intense in the latter compared to those of diabetics. The labeling
      density was quantified by evaluating the number and spatial distribution of gold
      particles within the granules. The number of gold particles was significantly
      lower in glands from diabetics than in control glands. CONCLUSIONS:  The results
      obtained suggest that a reduced statherin secretion by salivary glands might be
      partly responsible for a less effective protection of the oral tissues, resulting
      in an higher incidence of caries and oral infections associated with diabetes.

PMID- 20796228
TI  - The prevalence of tongue lesions in Malaysian dental outpatients from the Klang
      Valley area.
AB  - OBJECTIVES:  To determine the prevalence of tongue lesions in Malaysian dental
      outpatients from the Klang Valley area. SUBJECTS AND METHODS:  A cross sectional
      study was conducted on 600 Malaysian outpatients (257 men, 343 women, mean age,
      37.7 years) attending the Primary Dental Care Unit at the Faculty of Dentistry,
      University of Malaya. Demographic and medical data were recorded for all
      respondents. RESULTS:  One hundred eighty-one patients (30.2%) (81 men, 100
      women, mean age 42.0 years) were diagnosed with at least one tongue lesion (n =
      207) at the time of examination. Of these, 24 patients (4%) had two or more
      tongue lesions present synchronously. Seven different lesions were diagnosed:
      fissured tongue (13.8%), crenated tongue (7.8%), pigmented tongue (6.2%),
      geographic tongue (2.2%), ankyloglossia (1.7%), hairy tongue (1.0%) and median
      rhomboid glossitis (0.2%). Their racial prevalences were Malays (n = 65, 10.8%),
      Indians (n = 62, 10.3%), Chinese (n = 53, 8.8%) and other race (n = 1, 0.2%). A
      significant relationship was observed between crenated tongue and race; between
      four types of tongue lesions (fissured tongue, geographic tongue, crenated tongue
      and pigmented tongue) and age; and between fissured tongue and gender (P < 0.05).
      CONCLUSIONS: Distribution characteristics of tongue lesions in Malaysians are
      important as local reference data in the daily clinical practice.

PMID- 20796229
TI  - Stem cells and the repair of radiation-induced salivary gland damage.
AB  - Hyposalivation underlying xerostomia after radiotherapy is still a major problem
      in the treatment of head and neck cancer. Stem cell therapy may provide a means
      to reduce radiation-induced hyposalivation and improve the quality of life of
      patients. This review discusses the current status in salivary gland stem cell
      research with respect to their potential to attenuate salivary gland dysfunction.
      Knowledge on the embryonic development, homeostasis and regeneration after
      atrophy of the salivary glands has provided important knowledge on the location
      of the salivary gland as well as on the factors that influence proliferation and
      differentiation. This knowledge has helped to locate, isolate and characterize
      cell populations that contain the salivary gland stem cell, although the exact
      tissue stem cell is still unidentified. The role that stem/progenitor cells play
      in the response to radiation and the factors that can influence stem/progenitor
      induced proliferation and differentiation are discussed. Finally, the
      mobilization and transplantation of stem cells and supportive cells and their
      potential to attenuate radiation-induced salivary gland damage are discussed.
      Based on the major advances made in the field of stem cell research, stem cell
      based therapy has great potential to allow prevention or treatment of radiation
      induced hyposalivation.

PMID- 20796230
TI  - Tumour necrosis factor-alpha gene polymorphisms and susceptibility to oral lichen
      planus.
AB  - OBJECTIVE:  This study is aimed to investigate the association between OLP
      susceptibility and clinical type in the Thai population and three polymorphisms
      within the promoter region of the TNF-alpha at positions -863, -308 and -238
      which have putative functional significances. MATERIALS AND METHODS:  Genomic DNA
      from 75 Thai patients with OLP and 154 healthy controls were genotyped for TNF
      alpha polymorphisms-- -863(rs1800630), -308(rs1800629), and -238(rs361525)--using
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
      RESULTS:  We found a higher proportion of TNF-alpha-308 AA genotype (high
      producer genotype) among OLP patients (5/75; 6.67%) when compared to healthy
      controls (1/154; 0.65%; OR = 10.93; 95% CI = 1.21-251.9). For other polymorphisms
      (-863 and -238), we did not find any significant association with OLP
      development; this was also the case with haplotype analysis (-863/-308/-238).
      CONCLUSION:  TNF-alpha-308AA may play a relevant role in the susceptibility and
      severity of OLP in the Thai population. However, further investigation of this
      study is needed.

PMID- 20796231
TI  - Salivary osteocalcin levels are decreased in smoker chronic periodontitis
      patients.
AB  - OBJECTIVES:  This study was planned to investigate whether smoker chronic
      periodontitis patients exhibit different salivary concentrations of C-telopeptide
      pyridinoline cross-links of type I collagen (ICTP) and osteocalcin (OC) compared
      to the non-smoker counterparts. METHODS: Whole saliva samples, full-mouth
      clinical periodontal recordings were obtained from 33 otherwise healthy chronic
      periodontitis patients and 36 systemically, periodontally healthy control
      subjects. Chronic periodontitis patients and healthy control subjects were
      divided into smoker and non-smoker groups according to their self reports.
      Salivary ICTP, OC levels were determined by Enzyme-linked Immunoassays. RESULTS:
      Healthy control groups exhibited significantly lower values in all clinical
      periodontal measurements (P < 0.001). Smoker periodontitis patients revealed
      similar clinical periodontal index values with non-smoker counterparts (P >
      0.05). Chronic periodontitis patients exhibited significantly higher salivary OC
      levels than healthy controls (P < 0.05). Smoker periodontitis patients revealed
      lower salivary OC levels than non-smoker counterparts (P < 0.001). Log ICTP
      levels in non-smoker chronic periodontitis patients were higher than non-smoker
      controls (P < 0.05). Smoker healthy control group revealed higher log ICTP levels
      than non-smoker counterparts (P < 0.001). CONCLUSIONS: Within the limits of this
      study, it may be suggested that suppression of salivary osteocalcin level by
      smoking may at least partly explain the deleterious effects of smoking on
      periodontal status.

PMID- 20796232
TI  - Bisphosphonates affect migration ability and cell viability of HUVEC, fibroblasts
      and osteoblasts in vitro.
AB  - OBJECTIVES: Bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) is a side
      effect in patients being treated with bisphosphonates. The bisphosphonates most
      often associated with BP-ONJ are the highly potent nitrogen-containing
      bisphosphonates, e.g. pamidronate or zoledronate. In terms of BP-ONJ aetiology,
      several theories are being discussed: inhibition of bone remodelling, effect on
      soft tissues, and antiangiogenic effect of bisphosphonates. The aim of this in
      vitro study was to investigate the effect of different potent bisphosphonates on
      osteoblasts, fibroblasts and human umbilicord vein endothelial cells (HUVEC).
      MATERIALS AND METHODS: Three nitrogen-containing bisphosphonates (ibandronate,
      pamidronate and zoledronate) and one non-nitrogen-containing bisphosphonate
      (clodronate) were compared concerning their potency on apoptosis induction
      (tunel), cell viability (calcein assay) and migration potency (boyden chamber) on
      osteoblasts, fibroblasts and HUVEC. RESULTS:   The nitrogen-containing
      bisphosphonates, particularly pamidronate and zoledronate, affect cell viability,
      cell migration and the induction of apoptosis of osteoblasts, fibroblasts and
      HUVEC. CONCLUSIONS: These results support the theory that BP-ONJ is a
      multifactorially caused disease because several cell lines of the oral cavity
      which are responsible for integrity and wound healing are negatively affected by
      nitrogen-containing bisphosphonates. Perioperative interruption of bisphosphonate
      application during dental surgical procedures--if possible--might be feasible to
      promote better wound healing.

PMID- 20796233
TI  - Taste dysfunction: a practical guide for oral medicine.
AB  - Dental practitioners are often the first clinicians to be presented with
      complaints about changes in taste. This raises a problem in terms of appropriate
      evaluative response. It is a difficult issue both because of the common confusion
      between smell and taste problems (with smell being the more vulnerable sense and
      contributing substantially to the flavor of food that most patients equate with
      'taste'), and because of the lack of widely accepted standardized techniques to
      assess true taste function. This brief review provides a summary of some of the
      problems associated with assessing taste function in a clinical setting and of
      patient management options available to the practitioner of oral medicine.

PMID- 20796234
TI  - Self-reported acne severity, treatment, and belief patterns across multiple
      racial and ethnic groups in adolescent students.
AB  - Acne vulgaris is a common condition among adolescents regardless of age, gender,
      and race. We compare the frequency, severity, help-seeking behavior, treatment,
      and beliefs about acne among students based on race, ethnicity, gender, and age.
      Anonymous surveys were administered to 1,214 students aged 10-19 years of varied
      gender, race, and ethnicity in public middle and high schools in New Jersey.
      Results showed the frequency and severity of acne were high (76% and 65%,
      respectively) and more prevalent in white compared to non-white respondents (RR =
      1.13, 95% CI = 1.04-1.24 and RR = 1.22, 95% CI = 1.09-1.37, respectively), and
      also in older compared to younger ages (RR = 1.24, 95% CI = 1.17-1.32 and RR =
      1.43, 95% CI = 1.32-1.55, respectively). The majority of respondents (83%)
      reported never having seen a physician for their acne; however, those reporting
      acne of some severity were more likely to have seen a physician compared with
      those who did not report acne (21% vs. 8%, p < 0.001). Blacks who reported mild
      or moderate severity of acne were more likely to have seen a health professional
      compared to white respondents with same the acne severity (RR = 3.63, 95% CI =
      2.06-6.37 and RR = 3.06, 95% CI = 2.02-4.65, respectively). Conversely, Hispanic
      respondents with mild or moderate acne were less likely to have seen a health
      professional compared to whites with the same acne severity (RR = 0.56, 95% CI =
      0.35-0.89 and RR = 0.47, 95% CI = 0.26-0.86, respectively). Beliefs about
      external factors affecting acne also varied by race and ethnicity. In conclusion,
      the severity, frequency, and beliefs about acne all play a role in help-seeking
      behaviors, which vary to a significant extent by race and ethnicity.

PMID- 20796235
TI  - The Self-administered Eczema Area and Severity Index in children with moderate to
      severe atopic dermatitis: better estimation of AD body surface area than
      severity.
AB  - The Self-Administered Eczema Area and Severity Index (SA-EASI) is one of the few
      patient based atopic dermatitis (AD) disease activity scores and was found to be
      highly correlated with the EASI. Correlation with other frequently used scoring
      methods has not been investigated. The aim of this study was to evaluate the
      relation of the SA-EASI with two physician-based disease activity scores
      (objective SCORAD and SASSAD score) and with a serum marker for AD (Thymus and
      Activation-Regulated Cytokine [TARC]) in children with AD. Sixty children with
      moderate to severe AD were included. The SA-EASI was completed by caregivers, and
      the objective SCORAD and SASSAD scores were measured successively on the same day
      by a trained investigator. Blood for serum TARC measurement was drawn. The
      correlation between the SA-EASI and the objective SCORAD was high (rho = 0.61, p
      = <0.001), mainly based on high correlation between the body surface area (BSA)
      measurements of both scores (rho = 0.50, p = <0.001). The correlation with the
      SASSAD score (only severity measurement) was 0.43 (p = <0.001). The correlation
      with serum TARC levels was 0.46; p = <0.001, mainly based on the BSA score of the
      SA-EASI (rho = 0.42, p = <0.001). Parents may have more difficulty in scoring
      severity of AD than scoring BSA involved. Educating parents in severity scoring
      of AD may improve agreement of the SA-EASI and the objective SCORAD, TARC, and
      SASSAD score. Additional use of the SA-EASI in routine clinical practice or in
      trials may then facilitate more frequent but still accurate assessment of AD.

PMID- 20796236
TI  - Trichodysplasia spinulosa--a rare complication in immunosuppressed patients.
AB  - Immunosuppression is necessary in a large number of conditions to modify immune
      responses and control disease severity. It is a vital part of treatment regimes
      following organ and bone marrow transplants. However, the use of
      immunosuppressive drugs has been shown to cause infections with common and
      unusual pathogens. We present the case of a 5-year-old female heart transplant
      recipient. Nine months after the transplant, she developed a tender acneiform
      eruption on her face consisting of numerous small yellowish to pink papules and
      pustules. Many of the lesions had a central, firm, small spinulous excrescence or
      a central dell. Histopathology demonstrated abnormal maturation of the hair
      follicles, nucleated eosinophilic cells with trichohyalin granules. The clinical
      presentation and histological features were in keeping with trichodysplasia
      spinulosa, a rare complication in immunosuppressed subjects. Treatment trials
      included reduction of immunosuppression combined with topical and oral retinoids,
      topical acyclovir, and oral valganciclovir with limited success.

PMID- 20796237
TI  - Late evolution of giant verruciform xanthoma in the setting of CHILD syndrome.
AB  - Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD)
      syndrome is a rare X-linked dominant disorder that is characterized by peculiar
      cutaneous features commonly associated with skeletal and internal organ
      involvement. Cutaneous verruciform xanthoma is an uncommon cutaneous
      manifestation of congenital hemidysplasia with ichthyosiform erythroderma and
      limb defects syndrome. We present a case presenting with a late onset of a large
      verruciform xanthoma of the right foot, in addition to the more typical cutaneous
      features of congenital hemidysplasia with ichthyosiform erythroderma and limb
      defects syndrome.

PMID- 20796238
TI  - Disseminated cutaneous histoplasmosis in an immunocompetent child, relapsed with
      itraconazole, successfully treated with voriconazole.
AB  - We present a rare case of disseminated cutaneous histoplasmosis in an
      immunocompetent child who relapsed after treatment with amphotericin B followed
      by itraconazole and was successfully treated with voriconazole.

PMID- 20796239
TI  - Chronically recurrent and disseminated tinea faciei/corporis--autoinoculation
      from asymptomatic tinea capitis carriage.
AB  - We report clinical findings in a 12-year-old girl with long-term recurrent and
      disseminated multiple eruptions of tinea faciei and tinea corporis, which
      persisted for 10 years. Mycological examination revealed the dermatophyte
      Trichophyton tonsurans in both scale samples from the body lesions and in
      brushing samples from her asymptomatic scalp, suggesting that she was an
      asymptomatic dermatophyte carrier on the scalp, and autoinoculation of the
      dermatophyte was responsible for the recurrent and disseminated tinea
      faciei/corporis.

PMID- 20796240
TI  - Two cases of isolated anterior cervical hypertrichosis.
AB  - Two unrelated Hispanic females, ages 4 and 3 years, respectively, each presented
      with a solitary patch of excessive terminal hair growth in the midline of the
      neck. This rare form of congenital localized hypertrichosis, known as anterior
      cervical hypertrichosis, is reported here as an isolated defect with no other
      underlying abnormalities.

PMID- 20796241
TI  - Occurrence of pustular psoriasis after treatment of Crohn disease with
      infliximab.
AB  - We report a case of pustular psoriasis induced by anti-TNF-alpha therapy in a 12
      year-old boy with inflammatory bowel disease. This is a well-documented
      phenomenon but remains a clinical challenge, especially when presenting in the
      pediatric setting.

PMID- 20796242
TI  - Localized severe scleroderma: a retrospective study of 26 pediatric patients.
AB  - Juvenile localized scleroderma includes different conditions characterized by
      skin hardening with increased collagen deposition. Although juvenile localized
      scleroderma is considered a relatively benign disease, lesions may extend through
      the dermis, subcutaneous tissue, muscles, and the underlying bone, leading to
      significant functional and cosmetic deformities. Furthermore, extracutaneous
      manifestations are described. We retrospectively analyzed a cohort of 26 patients
      with severe Juvenile localized scleroderma with particular attention to clinical
      features, therapy, and long-term outcome. A subgroup of three patients has been
      further evaluated with infrared thermography. Our findings were consistent with
      the current literature for demographic, laboratory, and clinical characteristics
      at disease onset, but, with our patients, the prevalence of extracutaneous
      manifestations was higher, thus confirming the potential for severe juvenile
      localized scleroderma to affect organs other than the skin, without increased
      risk of development toward systemic sclerosis. Correlation between various
      treatments and clinical endpoint showed that systemic therapy lead to a better
      outcome: in particular, methotrexate appeared the most effective drug, capable in
      halting the progression of the disease and sometimes inducing its regression.

PMID- 20796243
TI  - Effect and mechanism of a new photodynamic therapy with glycoconjugated
      fullerene.
AB  - When irradiated, fullerene efficiently generates reactive oxygen species (ROS)
      and is an attractive photosensitizer for photodynamic therapy (PDT). Ideally,
      photosensitizers for PDT should be water-soluble and tumor-specific. Because
      cancer cells endocytose glucose more effectively than normal cells, the
      characteristics of fullerene as a photosensitizer were improved by combining it
      with glucose. The cytotoxicity of PDT was studied in several cancer cell lines
      cultured with C(60)-(Glc)1 (D-glucose residue pendant fullerene) and C(60)
      (6Glc)1 (a maltohexaose residue pendant fullerene) subsequently irradiated with
      UVA(1). PDT alone induced significant cytotoxicity. In contrast, PDT with the
      glycoconjugated fullerene exhibited no significant cytotoxicity against normal
      fibroblasts, indicating that PDT with these compounds targeted cancer cells. To
      investigate whether the effects of PDT with glycoconjugated fullerene were
      because of the generation of singlet oxygen ((1)O(2)), NaN(3) was added to cancer
      cells during irradiation. NaN(3) extensively blocked PDT-induced apoptosis,
      suggesting that PDT-induced cell death was a result of the generation of (1)O(2).
      Finally, to investigate the effect of PDT in vivo, melanoma-bearing mice were
      injected intratumorally with C(60)-(Glc)1 and irradiated with UVA(1). PDT with
      C(60)-(Glc)1 suppressed tumor growth. These findings indicate that PDT with
      glycoconjugated fullerene exhibits tumor-specific cytotoxicity both in vivo and
      in vitro via the induction of (1)O(2).

PMID- 20796244
TI  - Novel rare earth-polyvinyl pyridine complex functionalized hybrid silica
      microspheres: molecular assembly and photophysical property.
AB  - The functional silica microspheres are derived from the three different silane
      crosslinking reagents, and then the polyvinyl pyridine-based rare earth hybrids
      are synthesized through free radical copolymerization of rare earth-vinyl
      pyridine complex monomer with these functionalized silica microspheres (RE = Eu,
      Tb). The obtained hybrids are characterized by Fourier transform infrared, X-ray
      diffraction, Scanning electronic microscope and photoluminescence spectra. The
      intramolecular energy transfer process between rare earth ions and polymer
      polyvinyl pyrrolidone matrices took place within these polymer-based hybrids and
      especially the quantum efficiency of europium hybrids are determined, suggesting
      that the hybrid material systems derived from different functional silica
      microspheres present different luminescence efficiencies.

PMID- 20796245
TI  - Chloroplast genome sequences from total DNA for plant identification.
AB  - Chloroplast DNA sequence data are a versatile tool for plant identification or
      barcoding and establishing genetic relationships among plant species. Different
      chloroplast loci have been utilized for use at close and distant evolutionary
      distances in plants, and no single locus has been identified that can distinguish
      between all plant species. Advances in DNA sequencing technology are providing
      new cost-effective options for genome comparisons on a much larger scale.
      Universal PCR amplification of chloroplast sequences or isolation of pure
      chloroplast fractions, however, are non-trivial. We now propose the analysis of
      chloroplast genome sequences from massively parallel sequencing (MPS) of total
      DNA as a simple and cost-effective option for plant barcoding, and analysis of
      plant relationships to guide gene discovery for biotechnology. We present
      chloroplast genome sequences of five grass species derived from MPS of total DNA.
      These data accurately established the phylogenetic relationships between the
      species, correcting an apparent error in the published rice sequence. The
      chloroplast genome may be the elusive single-locus DNA barcode for plants.

PMID- 20796247
TI  - Ambiguous figures and binding: EEG frequency modulations during multistable
      perception.
AB  - Ambiguous figures induce sudden transitions between rivaling percepts. We
      investigated electroencephalogram frequency modulations of accompanying change
      related de- and rebinding processes. Presenting the stimuli discontinously, we
      synchronized perceptual reversals with stimulus onset, which served as a time
      reference for averaging. The resultant gain in temporal resolution revealed a
      sequence of time-frequency correlates of the reversal process. Most conspicuous
      was a transient right-hemispheric gamma modulation preceding endogenous reversals
      by at least 200 ms. No such modulation occurred with exogenously induced
      reversals of unambiguous stimulus variants. Post-onset components were delayed
      for ambiguous compared to unambiguous stimuli. The time course of oscillatory
      activity differed in several respects from predictions based on binding-related
      hypotheses. The gamma modulation preceding endogenous reversals may indicate an
      unstable brain state, ready to switch.

PMID- 20796246
TI  - Phospholipid and triacylglycerol profiles modified by PLD suppression in soybean
      seed.
AB  - Phospholipase D (PLD) is capable of hydrolyzing membrane phospholipids, producing
      phosphatidic acid. To alter phospholipid profiles in soybean seed, we attenuated
      PLD enzyme activity by an RNA interference construct using the partial sequence
      from a soybean PLDalpha gene. Two transgenic soybean lines were established by
      particle inflow gun (PIG) bombardment by co-bombarding with pSPLDi and pHG1
      vectors. The lines were evaluated for the presence and expression of transgenes
      thoroughly through the T(4) generation. PLD-suppressed soybean lines were
      characterized by decreased PLDalpha enzyme activity and decreased PLDalpha
      protein both during seed development and in mature seeds. There was no change in
      total phospholipid amount; however, the PLD-attenuated transgenic soybean seed
      had higher levels of di18:2 (dilinoleoyl)-phosphatidylcholine (PC) and 
      phosphatidylethanolamine (PE) in seeds than the non-transgenic lines. The
      increased polyunsaturation was at the expense of PC and PE species containing
      monounsaturated or saturated fatty acids. In addition to increased unsaturation
      in the phospholipids, there was a decrease in unsaturation of the triacylglycerol
      (TAG) fraction of the soybean seeds. Considering recent evidence for the notion
      that desaturation of fatty acids occurs in the PC fraction and that the PC->DAG
      (diacylglycerol)->TAG pathway is the major route of TAG biosynthesis in
      developing soybean seed, the current data suggest that PLDalpha suppression slows
      the conversion of PC to TAG. This would be consistent with PLD playing a positive
      role in that conversion. The data indicate that soybean PLD attenuation is a
      potentially useful approach to altering properties of edible and industrial
      soybean lecithin.

PMID- 20796248
TI  - Allergy is an important factor in asthma exacerbation: a pro/con debate.
AB  - Allergy and allergens have been implicated in asthma and it has historically been
      assumed that deteriorating asthma is related to allergen exposure. In the current
      pro/con debate some leading academics and researchers in the field consider this
      notion in the light of recent evidence. They conclude that allergy does not
      directly cause exacerbations but suggest that it may contribute to acute asthma
      in a different fashion. Possibilities that are proposed by the authors include
      specific allergy phenotypes acting as risk factors for virus-associated
      exacerbations or alternatively that allergy may be implicated in the blunted
      innate immune responses detected in asthma.

PMID- 20796249
TI  - Osteopontin levels are elevated in patients with eosinophilic pneumonia.
AB  - BACKGROUND AND OBJECTIVE: Osteopontin is a key cytokine involved in pro
      inflammatory T helper type 1 (Th1)-associated immune responses, which has
      recently been implicated in allergic diseases. We investigated the pathogenic
      role of osteopontin in eosinophilic pneumonia. METHODS: The concentrations of
      osteopontin and Th1- or Th2-associated cytokines were measured in BAL fluid
      (BALF) from 41 patients with eosinophilic pneumonia, including those with acute
      (AEP, n = 12), chronic (CEP, n = 16), or drug-induced eosinophilic pneumonia
      (DEP, n = 13). The results were compared with those from patients with other
      interstitial lung diseases. Immunocytochemistry and double immunofluorescence
      labelling were performed to determine the cellular source of osteopontin.
      RESULTS: Osteopontin was significantly elevated in BALF from patients with
      eosinophilic pneumonia as compared with BALF from patients with drug-induced
      interstitial pneumonia, hypersensitivity pneumonitis, idiopathic interstitial
      pneumonia, or sarcoidosis, and also compared with BALF from healthy volunteers.
      Osteopontin concentrations elevated at the time of exacerbation decreased during
      clinical improvement, either spontaneously or as a result of corticosteroid
      therapy. Elevated concentrations of CXCL10, CCL17 and IL-10 were also detected in
      BALF from patients with eosinophilic pneumonia. Osteopontin concentrations in
      BALF of AEP patients were correlated with IL-5, as well as IL-10, CCL11, CCL17
      and CXCL10 concentrations. In AEP and DEP patients, serum osteopontin
      concentrations were also elevated. Double immunofluorescence labelling showed
      that in patients with eosinophilic pneumonia, osteopontin was expressed in lung
      eosinophils. CONCLUSIONS: Osteopontin is likely to contribute to the development
      of inflammation in patients with eosinophilic pneumonia.

PMID- 20796250
TI  - The R30Q DLG5 variant is not associated with celiac disease or inflammatory bowel
      disease in the Spanish population.
AB  - Alterations in intestinal epithelial permeability could underlie inflammatory
      bowel disease (IBD) and celiac disease (CeD) etiology, as supported by previous
      association studies. One related gene, DLG5 [discs, large homologue 5
      (Drosophila)], has been associated with IBD in several populations and with CeD
      in the Dutch population. We tried to confirm the involvement of DLG5 in CeD
      performing a case-control study (725 CeD patients and 803 controls) by analysing
      the R30Q variant (rs1248696). Genetic frequencies did not significantly differ
      between groups (P > 0.80) and the meta-analysis with the Dutch data did not show
      any association. Additionally, we evaluated the effect of R30Q in IBD risk (858
      patients), as discordant results were previously obtained. No association was
      detected. Our study does not support the effect of the R30Q DLG5 variant in CeD
      or IBD predisposition in the Spanish population.

PMID- 20796251
TI  - Pooled peripheral blood mononuclear cells provide an optimized cellular substrate
      for human immunodeficiency virus Type 1 isolation during acute infection.
AB  - BACKGROUND: Cellular substrate (CS) composed of phytohemagglutinin (PHA)
      stimulated PBMNCs is required for isolating primary human immunodeficiency virus
      Type 1 from plasma (PHIV) during early acute infection. The transmitted founder
      PHIV is neutralization-sensitive and uses chemokine-receptor 5 to infect CD4
      positive PBMNCs. Therefore, PHIV cocultured with optimized CS would enable
      efficient virologic diagnosis, vaccine development, and tests for broadly
      neutralizing antibodies (bnAb). STUDY DESIGN AND METHODS: Fifteen leukapheresis
      donations were used to isolate CD4-enriched PBMNCs. Individual or three or four
      donors' pooled cells were stimulated with PHA, and both CSs were evaluated in
      parallel cocultures using five different PHIV isolates from nucleic acid testing
      positive anti-HIV-negative donations. Feasibility of coculturing PHIV with pooled
      PBMNC-CS after dimethyl sulfoxide cryopreservation was investigated. RESULTS: The
      cell-free supernatants from individual CSs contained mean HIV-p24 antigen varying
      between 20.35 and 85.54 ng/mL, while that from pooled CSs ranged between 57.54
      and 88.10 ng/mL. Thus, PBMNCs pooled from multiple donors provide an optimal CS
      for coculturing PHIV. Cryopreserved PBMNC-CS for PHIV cocultures is promising for
      systematic biosynthesis of PHIV. CONCLUSIONS: Pooled CSs after cryopreservation
      were functional for PHIV replication and enable on-demand diagnostic cocultures,
      preparing panels of PHIV stocks for bnAb testing and developing an envelope
      subunit vaccine candidate analogous to hepatitis B surface antigen, proven
      successful in preventing hepatitis B virus infection.

PMID- 20796252
TI  - Mitochondrial dysfunction of platelets stored in first- and second-generation
      containers is, in part, associated with elevated carbon dioxide levels.
AB  - BACKGROUND: The gas permeability of platelet (PLT) storage bags influences the
      retention of in vitro PLT parameters during storage. The aim of this study was to
      evaluate mitochondrial function of PLTs stored in first- and second-generation
      bags with different gas permeabilities. STUDY DESIGN AND METHODS: Identical whole
      blood-derived PLT concentrates were stored in second-generation CLX (Pall Corp.)
      and first-generation PL146 (Baxter Healthcare Corp.) bags (n = 12). PLTs were
      assayed for standard in vitro PLT assays as well as for mitochondrial membrane
      potential (MMP), accumulation of reactive oxygen species, Annexin V binding,
      mitochondrial mass, and activity of mitochondrial reduction power on Days 1, 4,
      5, 6, and 7. Results were analyzed by paired t test and by multiple regression
      analysis. RESULTS: With PLTs stored in PL146 bags that underwent large pH
      declines, there was greater superoxide production, greater peroxide accumulation,
      and greater mitochondrial membrane depolarization. Superoxide anion generation
      was correlated with higher levels of carbon dioxide (p = 0.0001) and lower oxygen
      levels (p = 0.0064; multiple regression R(2) = 0.9204). Changes in MMP were
      correlated with higher levels of carbon dioxide (p = 0.0288) and PLT activation
      (p = 0.0178; multiple regression R(2) = 0.9511). CONCLUSION: Prolonged periods of
      elevated carbon dioxide levels, potentially coupled with other factors, is
      associated with PLT mitochondria dysfunction and poor pH control during storage.

PMID- 20796253
TI  - Active cooling of whole blood to room temperature improves blood component
      quality.
AB  - BACKGROUND: Many countries use cooling plates to actively cool collected whole
      blood (WB) to room temperature. Until now, no paired comparison had been
      performed, and it was our aim to compare the effect of active versus no active
      cooling on the in vitro quality of WB and subsequently prepared blood components.
      STUDY DESIGN AND METHODS: Two units of WB were pooled and divided shortly after
      donation. One unit was placed under a butane-1,4-diol plate to obtain active
      cooling; the other was placed in an insulated box with other warm units to mimic
      worst-case holding conditions. WB was held overnight and processed into a white
      blood cell (WBC)-reduced red blood cells (RBCs), buffy coat (BC), and plasma. The
      BCs were further processed into platelet (PLT) concentrates. RBCs were stored for
      42 days, and PLT concentrates for 8 days (n = 12 paired experiments). RESULTS:
      After overnight storage, ATP content of the RBCs was 4.9 +/- 0.3 umol/g Hb for
      actively cooled WB versus 4.5 +/- 0.4 umol/g Hb for not actively cooled WB (p <
      0.001). On Day 42 of storage, RBCs prepared from this WB contained 3.1 +/- 0.3
      umol ATP/g Hb with active cooling versus 2.6 +/- 0.3 umol/g Hb without (p <
      0.001). Hemolysis on Day 42 was 0.35 +/- 0.08% with active cooling and 0.67 +/-
      0.21% without (p < 0.001). No effect was observed on the in vitro quality of
      plasma, BC, or PLT concentrates. CONCLUSIONS: Active cooling of WB results in
      improved ATP levels and less hemolysis in WBC-reduced RBCs, although the clinical
      implications are unclear. It has no effect on the in vitro quality of plasma or
      PLT concentrates.

PMID- 20796255
TI  - Transcameral suture for tube cornea touch.

PMID- 20796254
TI  - Comparison of platelet transfusion as fresh whole blood versus apheresis
      platelets for massively transfused combat trauma patients (CME).
AB  - BACKGROUND: At major combat hospitals, the military is able to provide blood
      products to include apheresis platelets (aPLT), but also has extensive experience
      using fresh whole blood (FWB). In massively transfused trauma patients, we
      compared outcomes of patients receiving FWB to those receiving aPLT. STUDY DESIGN
      AND METHODS: This study was a retrospective review of casualties at the military
      hospital in Baghdad, Iraq, between January 2004 and December 2006. Patients
      requiring massive transfusion (>=10 units in 24 hr) were divided into two groups:
      those receiving FWB (n = 85) or aPLT (n = 284) during their resuscitation.
      Admission characteristics, resuscitation, and survival were compared between
      groups. Multivariate regression analyses were performed comparing survival of
      patients at 24 hours and at 30 days. Secondary outcomes including adverse events
      and causes of death were analyzed. RESULTS: Unadjusted survival between groups
      receiving aPLT and FWB was similar at 24 hours (84% vs. 81%, respectively; p =
      0.52) and at 30 days (60% versus 57%, respectively; p = 0.72). Multivariate
      regression failed to identify differences in survival between patients receiving
      PLT transfusions either as FWB or as aPLT at 24 hours or at 30 days. CONCLUSIONS:
      Survival for massively transfused trauma patients receiving FWB appears to be
      similar to patients resuscitated with aPLT. Prospective trials will be necessary
      before consideration of FWB in the routine management of civilian trauma.
      However, in austere environments where standard blood products are unavailable,
      FWB is a feasible alternative.

PMID- 20796256
TI  - Chiasm-compressing rhabdomyosarcoma in a patient presumed to have juvenile-onset
      open-angle glaucoma.

PMID- 20796257
TI  - Intraocular safari: ophthalmomyiasis interna.

PMID- 20796259
TI  - Retinal haemorrhages in inflicted brain injury: the ophthalmologist in court -
      comment.

PMID- 20796260
TI  - Comparison of two ophthalmoscopes for direct ophthalmoscopy.
AB  - BACKGROUND: To measure the ease of use and performance of the Optyse lens-free
      ophthalmoscope compared with the standard Keeler pocket ophthalmoscope, and to
      assess its suitability as an inexpensive ophthalmoscope for medical students.
      DESIGN: Randomized cross-over study. PARTICIPANTS: Twenty second-year medical
      students, 10 as ophthalmoscopists ('observers') and 10 as 'patients'. METHODS:
      Students used both ophthalmoscopes to examine the optic disc in each eye of 10
      'patients'. They were randomized as to the order in which they were used. A
      Consultant ophthalmologist was used as the gold standard. MAIN OUTCOME MEASURES:
      Main outcome measures were accuracy in estimating vertical cup:disc ratio (VCDR),
      ease of use (EOU) for each examination, and overall ease of use (OEOU). RESULTS:
      Of 400 attempted eye examinations, sufficient visualization was achieved in 220
      cases to allow a VCDR estimation: 107/200 VCDR estimates with the Optyse and
      113/200 with the Keeler. Accuracy of VCDR estimates was better with the Optyse by
      the equivalent of 0.05 VCDR (P = 0.002). There was no significant difference in
      EOU or OEOU between the two ophthalmoscopes. EOU for 400 examinations: median
      (IQR) of 6 (3-8) for Optyse versus 6 (3-8) for Keeler (P = 0.648). OEOU for 20
      scores: median (IQR) of 6.5 (2-9) for Optyse versus 5.5 (3-8) for Keeler (P =
      0.21). CONCLUSION: Medical students found the Optyse and Keeler pocket
      ophthalmoscopes to be of similar ease of use and performed slightly better with
      the Optyse when estimating VCDR. The lens-free Optyse ophthalmoscope is a
      reasonable alternative to the standard Keeler pocket ophthalmoscope.

PMID- 20796261
TI  - In vitro compatibility study of cephalosporin with intraocular irrigating
      solutions and intracameral medications.
AB  - BACKGROUND: To study the compatibility of cephalosporins with intraocular
      irrigating solutions and intracameral medications commonly used in cataract
      surgery. DESIGN: The was an in vitro experiment conducted in the Research
      Laboratory of the Department of Microbiology, the Chinese University of Hong
      Kong, Prince of Wales Hospital, Shatin, Hong Kong. SAMPLES: Three cephalosporins-
      cefazolin, cefuroxime and ceftazidime--were separately diluted and mixed with
      irrigating solutions and intracameral medications to form 192 samples and 12
      control solutions. METHODS: The cephalosporins were dissolved in normal saline
      and further diluted to the concentration of 1 mg in 0.1 mL with normal saline,
      Ringer's solution, balanced salt solution and fortified balanced salt solutions.
      These were mixed with balanced salt solutions or fortified balanced salt
      solutions, with adrenaline, acetylcholine or carbachol and kept at 37 degrees C
      for 2 h. The concentrations of free cephalosporins were measured with rapid high
      performance liquid chromatography at baseline (0 h) and at 2 h. MAIN OUTCOME
      MEASURES: Free concentrations of cephalosporins at 2 h were compared with mean
      baseline (0 h) value. A difference of 3 standard deviations or more was
      considered statistically significant. RESULTS: At 2 h there was a significant
      drop in the cefuroxime concentration in preparations in which cefuroxime was
      diluted with normal saline (P < 0.01). In all preparations, the final
      concentrations of cephalosporins were higher than the minimal inhibitory
      concentrations (MIC(90)) for microbials commonly isolated from the external eye.
      CONCLUSION: Cefazolin, cefuroxime and ceftazidime were compatible with irrigating
      solutions and intracameral medications commonly used in cataract surgery.

PMID- 20796262
TI  - Urrets-Zavalia syndrome following Descemet's stripping endothelial keratoplasty
      triple procedure.

PMID- 20796263
TI  - Ophthalmic manifestations and risk factors for mortality of HIV patients in the
      post-highly active anti-retroviral therapy era.
AB  - BACKGROUND: To evaluate the ophthalmic manifestations and risk factors for
      mortality in HIV patients in the post-highly active anti-retrovirus therapy
      (HAART) era. DESIGN: Retrospective study. SAMPLES: 151 patients with HIV
      infection. METHODS: Review of all HIV patients who have attended the Hong Kong
      Eye Hospital between 2000 and 2007. MAIN OUTCOME MEASURES: Ocular findings
      especially opportunistic infections and medical information including mortality
      during follow up. RESULTS: At presentation, 139 (92.1%) patients were already
      diagnosed with HIV and 58 (41.7%) had an AIDS indicator condition. Fifty-one
      (33.8%) patients had HIV-related eye disease on presentation and the leading
      manifestations were cytomegalovirus (CMV) retinitis and HIV microangiopathy. Low
      baseline CD4 cell count <100 cells/L was significantly related with HIV-related
      ophthalmic manifestations and CMV retinitis at presentation (P < 0.013). 105
      patients were followed for 6 months or more and the mean follow-up was 4.8 years.
      There was no significant change in visual acuity compared with baseline (P =
      0.13). 20 (19.0%) patients had one eye with final visual acuity of 20/200 or
      worse and the leading cause for poor vision was CMV retinitis. 11 (10.5%)
      patients died during the follow-up due to complications of HIV/AIDS. The presence
      of HIV retinal microangiopathy was significantly associated with mortality (P =
      0.005). CONCLUSIONS: CMV retinitis remains the main HIV-related ocular disease in
      the post-HAART era. HIV retinal microangiopathy might be an important prognostic
      factor for mortality. Appropriate ophthalmic monitoring is justified to detect
      for ophthalmic complications in HIV patients regardless of HAART use in order for
      prompt initiation of treatment.

PMID- 20796264
TI  - Efficacy of wide-field digital retinal imaging for retinopathy of prematurity
      screening.
AB  - BACKGROUND: To evaluate the efficacy of wide-field digital retinal imaging for
      retinopathy of prematurity screening. DESIGN: Retrospective study in a quaternary
      public neonatal intensive care unit. PARTICIPANTS: A total of 108 premature
      infants screened for retinopathy of prematurity. METHODS: Retrospective chart and
      photo review were performed on participants screened by both serial wide-field
      digital retinal imaging and concurrent binocular indirect ophthalmoscopy. Review
      of captured digital photos was performed independently by a masked reader. Using
      the binocular indirect ophthalmoscopy findings as the gold standard, the efficacy
      of wide-field digital retinal imaging in detecting treatment-requiring
      retinopathy of prematurity, defined as type 1 prethreshold disease, was
      determined. MAIN OUTCOME MEASURES: Sensitivity and specificity of wide-field
      digital retinal imaging in detecting treatment-requiring retinopathy of
      prematurity. RESULTS: Treatment-requiring retinopathy of prematurity was detected
      in 11 infants by both binocular indirect ophthalmoscopy examination and
      telemedicine images taken at the same visit. Wide-field digital retinal imaging
      has a sensitivity of 100% (95% CI: 76.2-100%) and a specificity of 97.9% (95% CI:
      93.4-99.7%) in detecting infants with treatment-requiring retinopathy of
      prematurity. Positive and negative predictive values of wide-field digital
      retinal imaging were 84.6% (95% CI: 57.8-97.3%) and 100% (95% CI: 96.9-100%),
      respectively. CONCLUSIONS: Wide-field digital retinal imaging is accurate,
      reliable and efficient in detecting treatment-requiring retinopathy of
      prematurity. Incorporating wide-field digital retinal imaging with telemedicine
      in standard retinopathy of prematurity management can potentially improve
      delivery, accessibility, quality and cost of retinopathy of prematurity care.

PMID- 20796265
TI  - Relationships between anopheline mosquitoes and topography in West Timor and
      Java, Indonesia.
AB  - BACKGROUND: Malaria is a serious health issue in Indonesia. Mosquito control is
      one aspect of an integrated malaria management programme. To focus resources on
      priority areas, information is needed about the vectors and their habitats. This
      research aimed to identify the relationship between anopheline mosquitoes and
      topography in West Timor and Java. METHODS: Study areas were selected in three
      topographic types in West Timor and Java. These were: coastal plain, hilly (rice
      field) and highland. Adult mosquitoes were captured landing on humans identified
      to species level and counted. RESULTS: Eleven species were recorded, four of
      which were significant for malaria transmission: Anopheles aconitus, Anopheles
      barbirostris, Anopheles subpictus and Anopheles sundaicus. Each species occupied
      different topographies, but only five were significantly associated: Anopheles
      annularis, Anopheles vagus and Anopheles subpictus (Java only) with hilly rice
      fields; Anopheles barbirostris, Anopheles maculatus and Anopheles subpictus (West
      Timor only) with coastal areas. CONCLUSION: Information on significant malaria
      vectors associated with specific topography is useful for planning the mosquito
      control aspect of malaria management.

PMID- 20796267
TI  - Burden of anemia in patients with osteoarthritis and rheumatoid arthritis in
      French secondary care.
AB  - BACKGROUND: Arthritic disorders can be the cause of hospitalizations, especially
      among individuals 60 years and older. The objective of this study is to
      investigate associations between health care resource utilization in arthritis
      patients with and without concomitant anemia in a secondary care setting in
      France. METHODS: This retrospective cohort study utilized data on secondary care
      activity in 2001 from the Programme de Medicalisation des Systemes d'Information
      database. Two cohorts were defined using ICD-10 codes: patients with an arthritis
      diagnosis with a concomitant diagnosis of anemia; and arthritis patients without
      anemia. Health care resource utilization for both populations was analyzed
      separately in public and private hospitals. Study outcomes were compared between
      the cohorts using standard bivariate and multivariable methods. RESULTS: There
      were 300,865 hospitalizations for patients with arthritis only, and 2,744 for
      those with concomitant anemia. Over 70% of patients with concomitant anemia were
      in public hospitals, compared with 53.5% of arthritis-only patients. Arthritis
      patients without anemia were younger than those with concomitant anemia (mean age
      66.7 vs 74.6, public hospitals; 67.1 vs 72.2, private hospitals). Patients with
      concomitant anemia/arthritis only had a mean length of stay of 11.91 (SD
      14.07)/8.04 (SD 9.93) days in public hospitals, and 10.68 (SD 10.16)/9.83 (SD
      7.76) days in private hospitals. After adjusting for confounders, the mean (95%
      CI) additional length of stay for arthritis patients with concomitant anemia,
      compared with those with arthritis only, was 1.56 (1.14-1.98) days in public and
      0.69 (0.22-1.16) days in private hospitals. Costs per hospitalization were ?;480
      (227-734) greater for arthritis patients with anemia in public hospitals, and
      ?;30 (-113-52) less in private hospitals, than for arthritis-only patients.
      CONCLUSIONS: Arthritis patients with concomitant anemia have a longer length of
      stay, undergo more procedures, and have higher hospitalization costs than
      nonanemic arthritis patients in public hospitals in France. In private hospitals,
      concomitant anemia was associated with modest increases in length of stay and
      number of procedures; however, this did not translate into higher costs. Such
      evidence of anemia-related health care utilization and costs can be considered as
      a proxy for the clinical significance of anemia.

PMID- 20796266
TI  - Sexual dimorphism in the lasting effects of moderate caloric restriction during
      gestation on energy homeostasis in rats is related with fetal programming of
      insulin and leptin resistance.
AB  - AIM: We aimed to characterize the lasting effect of moderate caloric restriction
      during early pregnancy on offspring energy homeostasis, by focusing on the
      effects on food intake and body weight as well as on the insulin and leptin
      systems. METHODS: Male and female offspring of 20% caloric restricted dams (from
      1 to 12 days of pregnancy) (CR) and from control dams were studied. These animals
      were fed after weaning with a normal-fat (NF) diet until the age of 4 months, and
      then moved to a high-fat (HF) diet. Blood parameters were measured under fed and
      14-h fasting conditions at different ages (2, 4 and 5 months). Food preferences
      were also assessed in adult animals. RESULTS: Accumulated caloric intake from
      weaning to the age of 5 months was higher in CR animals compared with their
      controls, and this resulted in higher body weight in adulthood in males, but not
      in females. Both male and female CR animals already showed higher insulin levels
      at the age of 2 months, under fed conditions, and higher HOMA-IR from the age of
      4 months, compared with their controls. CR male animals, but not females,
      displayed higher preference for fat-rich food than their controls in adulthood
      and higher circulating leptin levels when they were under HF diet. CONCLUSION: It
      is suggested that hyperinsulinemia may play a role in the etiology of hyperphagia
      in the offspring of caloric restricted animals during gestation, with different
      outcomes on body weight depending on the gender, which could be associated with
      different programming effects on later leptin resistance.

PMID- 20796268
TI  - Accuracy of cardiovascular magnetic resonance in myocarditis: comparison of MR
      and histological findings in an animal model.
AB  - BACKGROUND: Because endomyocardial biopsy has low sensitivity of about 20%, it
      can be performed near to myocardium that presented as late gadolinium enhancement
      (LGE) in cardiovascular magnetic resonance (CMR). However the important issue of
      comparing topography of CMR and histological findings has not yet been
      investigated. Thus the current study was performed using an animal model of
      myocarditis. RESULTS: In 10 male Lewis rats experimental autoimmune myocarditis
      was induced, 10 rats served as control. On day 21 animals were examined by CMR to
      compare topographic distribution of LGE to histological inflammation.
      Sensitivity, specificity, positive and negative predictive values for LGE in
      diagnosing myocarditis were determined for each segment of myocardium. Latter
      diagnostic values varied widely depending on topographic distribution of LGE and
      inflammation as well as on the used CMR sequence. Sensitivity of LGE was up to
      76% (left lateral myocardium) and positive predictive values were up to 85% (left
      lateral myocardium), whereas sensitivity and positive predictive value dropped to
      0-33% (left inferior myocardium). CONCLUSIONS: Topographic distribution of LGE
      and histological inflammation seem to influence sensitivity, specificity,
      positive and negative predictive values. Nevertheless, positive predictive value
      for LGE of up to 85% indicates that endomyocardial biopsy should be performed "MR
      guided". LGE seems to have greater sensitivity than endomyocardial biopsy for the
      diagnosis of myocarditis.

PMID- 20796269
TI  - Low birth weight in offspring of women with depressive and anxiety symptoms
      during pregnancy: results from a population based study in Bangladesh.
AB  - BACKGROUND: There is a high prevalence of antepartum depression and low birth
      weight (LBW) in Bangladesh. In high- and low-income countries, prior evidence
      linking maternal depressive and anxiety symptoms with infant LBW is conflicting.
      There is no research on the association between maternal mental disorders and LBW
      in Bangladesh. This study aims to investigate the independent effect of maternal
      antepartum depressive and anxiety symptoms on infant LBW among women in a rural
      district of Bangladesh. METHODS: A population-based sample of 720 pregnant women
      from two rural subdistricts was assessed for symptoms of antepartum depression,
      using the Edinburgh Postpartum Depression Scale (EPDS), and antepartum anxiety,
      using the State Trait Anxiety Inventory (STAI), and followed for 6-8 months
      postpartum. Infant birth weight of 583 (81%) singleton live babies born at term
      (>= 37 weeks of pregnancy) was measured within 48 hours of delivery. Baseline
      data provided socioeconomic, anthropometric, reproductive, obstetric, and social
      support information. Trained female interviewers carried out structured
      interviews. Chi-square, Fisher's exact, and independent-sample t tests were done
      as descriptive statistics, and a multiple logistic regression model was used to
      identify predictors of LBW. RESULTS: After adjusting for potential confounders,
      depressive (OR = 2.24; 95% CI 1.37-3.68) and anxiety (OR = 2.08; 95% CI 1.30
      3.25) symptoms were significantly associated with LBW (<= 2.5 kg). Poverty,
      maternal malnutrition, and support during pregnancy were also associated with
      LBW. CONCLUSIONS: This study provides evidence that maternal depressive and
      anxiety symptoms during pregnancy predict the LBW of newborns and replicates
      results found in other South Asian countries. Policies aimed at the detection and
      effective management of depressive and anxiety symptoms during pregnancy may
      reduce the burden on mothers and also act as an important measure in the
      prevention of LBW among offspring in Bangladesh.

PMID- 20796270
TI  - Molecular epidemiology of Hepatitis C virus genotypes in Khyber Pakhtoonkhaw of
      Pakistan.
AB  - Six major Hepatitis C virus (HCV) genotypes and hundreds of subtypes have been
      identified globally. All these genotypes are generally studied for epidemiology,
      their vaccine development and clinical management. This article comments the
      frequency distribution of various HCV genotypes circulate in different
      areas/districts of Khyber Pakhtoonkhaw Province of Pakistan. Sum of 415 HCV RNA
      PCR positive sera samples were tested by a molecular genotyping assay. Data
      analysis revealed that out of these 415 HCV RNA positive patients 243 were males
      and 172 were females. Distribution breakup of the patients was 135, 58, 51, 51,
      36, 32, 6, 7 and 9 patients come from the districts of Abbottabad, Mardan,
      Pehawar, Swat, Haripure, Swabi and Dera Ismail Khan, respectively. Out of the
      tested samples, genotype specific PCR fragments were observed in 299 (74.82%)
      patient serum samples. The distribution of genotypes of the typeable samples was
      as follows: 3 patients (0.72%) each were infected with genotype 1a and genotype
      1b; 240 patients (80.26%) of genotype 3a; 25 patients (6.00%) genotype 3b; and 28
      patients (6.73%) were observed as with mixed genotypic infection. Sums of 116
      serum samples (27.88%) were still found untypeable by the used molecular
      genotyping system. In conclusion, HCV genotypes 1a, 1b, 3a and 3b are distributed
      in various parts of KPK among which the genotype 3a is the most frequent
      genotype.

PMID- 20796271
TI  - Problems encountered with the use of simulation in an attempt to enhance
      interpretation of a secondary data source in epidemiologic mental health
      research.
AB  - BACKGROUND: The longitudinal epidemiology of major depressive episodes (MDE) is
      poorly characterized in most countries. Some potentially relevant data sources
      may be underutilized because they are not conducive to estimating the most
      salient epidemiologic parameters. An available data source in Canada provides
      estimates that are potentially valuable, but that are difficult to apply in
      clinical or public health practice. For example, weeks depressed in the past year
      is assessed in this data source whereas episode duration would be of more
      interest. The goal of this project was to derive, using simulation, more readily
      interpretable parameter values from the available data. FINDINGS: The data source
      was a Canadian longitudinal study called the National Population Health Survey
      (NPHS). A simulation model representing the course of depressive episodes was
      used to reshape estimates deriving from binary and ordinal logistic models (fit
      to the NPHS data) into equations more capable of informing clinical and public
      health decisions. Discrete event simulation was used for this purpose. Whereas
      the intention was to clarify a complex epidemiology, the models themselves needed
      to become excessively complex in order to provide an accurate description of the
      data. CONCLUSIONS: Simulation methods are useful in circumstances where a
      representation of a real-world system has practical value. In this particular
      scenario, the usefulness of simulation was limited both by problems with the data
      source and by inherent complexity of the underlying epidemiology.

PMID- 20796272
TI  - Coronary artery bypass surgery in a patient with Kartagener syndrome: a case
      report and literature review.
AB  - Kartagener syndrome consists of congenital bronchiectasis, sinusitis, and total
      situs inversus in half of the patients. A patient diagnosed with Kartagener
      syndrome was referred to our department due to 3-vessel coronary disease. An off
      pump coronary artery bypass operation was performed using both internal thoracic
      arteries and a saphenous vein graft. We performed a literature review for cases
      with Kartagener syndrome, coronary surgery and dextrocardia. Although a few cases
      of dextrocardia were found in the literature, no case of Kartagener syndrome was
      mentioned.

PMID- 20796273
TI  - Ethnoveterinary plant remedies used by Nu people in NW Yunnan of China.
AB  - BACKGROUND: Nu people are the least populous ethnic group in Yunnan Province of
      China and most are distributed in Gongshan County, NW Yunnan. Animal production
      plays an important role in Nu livelihoods and the Nu people have abundant
      traditional knowledge of animal management and ethnoveterinary practices. This
      study documents the animal diseases, ethnoveterinary plant remedies and related
      traditional knowledge in three Nu villages of Gongshan County. METHODS: This
      study was carried out in three Nu villages of Gongshan County between July 2009
      and February 2010. Data was obtained through the use of semi-structured
      questionnaires, field observation and PRA tools. A total of 60 Nu respondents (34
      men and 26 women) provided information on animal ailments and ethnoveterinary
      plant medicines used for Nu livestock production. Information on traditional
      ethnoveterinary medicine knowledge and choice of treatment providers was also
      obtained. RESULTS: Thirty-five animal conditions were identified in the surveyed
      area. The major and most common animal diseases among livestock were skin
      conditions, diarrhea, heat, fevers, colds, and parasites. Most ailments occurred
      between June and August. The ethnoveterinary medicinal use of 45 plant species
      was documented. Most medicinal species (86.7%) were collected from the wild. The
      most frequently used plant parts were whole plants (35.6%), followed by roots
      (22.2%). The most important medicinal plant species were Saussurea costus (Falc.)
      Lipech. (UV = 0.67), Senecio scandens Buch.-Ham.ex D.Don (UV = 0.67), Plantago
      depressa Willd. (UV = 0.63), Rubus corchorifolius L. f. (UV = 0.62), Bupleurum
      yunnanense Franch. (UV = 0.60), and Polygonum paleaceum Wall. (UV = 0.60). Animal
      diseases treated with the highest number of ethnoveterinary plant remedies were
      diarrhea (16 plant species), heat, fever, colds (11 plant species), retained
      afterbirth (11 plant species), and skin conditions and sores (11 plant species).
      Many Nu villagers (52%) considered traditional remedies their first choice of
      animal disease treatment. Traditional ethnoveterinary knowledge was related to
      the local social-cultural characteristics of Nu people and communities.
      CONCLUSION: Animal production plays an important role in Nu culture and
      livelihoods, and the Nu ethnic group has abundant traditional knowledge about
      animal production and ethnoveterinary plant remedies. This traditional knowledge
      faces the risk of disappearing due to increasing modern veterinary medicine
      extension, livelihood changes and environment degradation. Animal diseases are a
      major constraint in livestock production in Nu villages. Thus, some strategies
      and measures should be adopted in the future, such as further researches on Nu
      culture and livelihoods, community-based validation of ethnoveterinary medicine
      and broad network building and knowledge sharing.

PMID- 20796274
TI  - Bioconversion of D-galacturonate to keto-deoxy-L-galactonate (3-deoxy-L-threo-hex
      2-ulosonate) using filamentous fungi.
AB  - BACKGROUND: The D-galacturonic acid derived from plant pectin can be converted
      into a variety of other chemicals which have potential use as chelators,
      clarifiers, preservatives and plastic precursors. Among these is the deoxy-keto
      acid derived from L-galactonic acid, keto-deoxy-L-galactonic acid or 3-deoxy-L
      threo-hex-2-ulosonic acid. The keto-deoxy sugars have been found to be useful
      precursors for producing further derivatives. Keto-deoxy-L-galactonate is a
      natural intermediate in the fungal D-galacturonate metabolic pathway, and thus
      keto-deoxy-L-galactonate can be produced in a simple biological conversion.
      RESULTS: Keto-deoxy-L-galactonate (3-deoxy-L-threo-hex-2-ulosonate) accumulated
      in the culture supernatant when Trichoderma reesei Deltalga1 and Aspergillus
      niger DeltagaaC were grown in the presence of D-galacturonate. Keto-deoxy-L
      galactonate accumulated even if no metabolisable carbon source was present in the
      culture supernatant, but was enhanced when D-xylose was provided as a carbon and
      energy source. Up to 10.5 g keto-deoxy-L-galactonate l(-1) was produced from 20 g
      D-galacturonate l(-1) and A. niger DeltagaaC produced 15.0 g keto-deoxy-L
      galactonate l(-1) from 20 g polygalacturonate l(-1), at yields of 0.4 to 1.0 g
      keto-deoxy-L-galactonate [g D-galacturonate consumed](-1). Keto-deoxy-L
      galactonate accumulated to concentrations of 12 to 16 g l(-1) intracellularly in
      both producing organisms. This intracellular concentration was sustained
      throughout production in A. niger DeltagaaC, but decreased in T. reesei.
      CONCLUSIONS: Bioconversion of D-galacturonate to keto-deoxy-L-galactonate was
      achieved with both A. niger DeltagaaC and T. reesei Deltalga1, although
      production (titre, volumetric and specific rates) was better with A. niger than
      T. reesei. A. niger was also able to produce keto-deoxy-L-galactonate directly
      from pectin or polygalacturonate demonstrating the feasibility of simultaneous
      hydrolysis and bioconversion. Although keto-deoxy-L-galactonate accumulated
      intracellularly, concentrations above ~12 g l(-1) were exported to the culture
      supernatant. Lysis may have contributed to the release of keto-deoxy-L
      galactonate from T. reesei mycelia.

PMID- 20796275
TI  - A bootstrap approach for assessing the uncertainty of outcome probabilities when
      using a scoring system.
AB  - BACKGROUND: Scoring systems are a very attractive family of clinical predictive
      models, because the patient score can be calculated without using any data
      processing system. Their weakness lies in the difficulty of associating a
      reliable prognostic probability with each score. In this study a bootstrap
      approach for estimating confidence intervals of outcome probabilities is
      described and applied to design and optimize the performance of a scoring system
      for morbidity in intensive care units after heart surgery. METHODS: The bias
      corrected and accelerated bootstrap method was used to estimate the 95%
      confidence intervals of outcome probabilities associated with a scoring system.
      These confidence intervals were calculated for each score and each step of the
      scoring-system design by means of one thousand bootstrapped samples. 1090
      consecutive adult patients who underwent coronary artery bypass graft were
      assigned at random to two groups of equal size, so as to define random training
      and testing sets with equal percentage morbidities. A collection of 78
      preoperative, intraoperative and postoperative variables were considered as
      likely morbidity predictors. RESULTS: Several competing scoring systems were
      compared on the basis of discrimination, generalization and uncertainty
      associated with the prognostic probabilities. The results showed that confidence
      intervals corresponding to different scores often overlapped, making it
      convenient to unite and thus reduce the score classes. After uniting two adjacent
      classes, a model with six score groups not only gave a satisfactory trade-off
      between discrimination and generalization, but also enabled patients to be
      allocated to classes, most of which were characterized by well separated
      confidence intervals of prognostic probabilities. CONCLUSIONS: Scoring systems
      are often designed solely on the basis of discrimination and generalization
      characteristics, to the detriment of prediction of a trustworthy outcome
      probability. The present example demonstrates that using a bootstrap method for
      the estimation of outcome-probability confidence intervals provides useful
      additional information about score-class statistics, guiding physicians towards
      the most convenient model for predicting morbidity outcomes in their clinical
      context.

PMID- 20796276
TI  - The PI3K/Akt pathway upregulates Id1 and integrin alpha4 to enhance recruitment
      of human ovarian cancer endothelial progenitor cells.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) contribute to tumor angiogenesis
      and growth. We aimed to determine whether inhibitors of differentiation 1 (Id1)
      were expressed in circulating EPCs of patients with ovarian cancer, whether Id1
      could mediate EPCs mobilization and recruitment, and, if so, what underlying
      signaling pathway it used. METHODS: Circulating EPCs cultures were from 25
      patients with ovarian cancer and 20 healthy control subjects. Id1 and integrin
      alpha4 expression were analyzed by real-time reverse transcription-polymerase
      chain reaction and western blot. EPCs proliferation, migration, and adhesion were
      detected by MTT, transwell chamber, and EPCs-matrigel adhesion assays. Double
      stranded DNA containing the interference sequences were synthesized according to
      the structure of a pGCSIL-GFP viral vector and then inserted into a linearized
      vector. Positive clones were identified as lentiviral vectors that expressed
      human Id1 short hairpin RNA (shRNA). RESULTS: Id1 and integrin alpha4 expression
      were increased in EPCs freshly isolated from ovarian cancer patients compared to
      those obtained from healthy subjects. siRNA-mediated Id1 downregulation
      substantially reduced EPCs function and integrin alpha4 expression. Importantly,
      Inhibition of PI3K/Akt inhibited Id1 and integrin alpha4 expression, resulting in
      the decreasing biological function of EPCs. CONCLUSIONS: Id1 induced EPCs
      mobilization and recruitment is mediated chiefly by the PI3K/Akt signaling
      pathway and is associated with activation of integrin alpha4.

PMID- 20796277
TI  - A mixed community of actinomycetes produce multiple antibiotics for the fungus
      farming ant Acromyrmex octospinosus.
AB  - BACKGROUND: Attine ants live in an intensely studied tripartite mutualism with
      the fungus Leucoagaricus gongylophorus, which provides food to the ants, and with
      antibiotic-producing actinomycete bacteria. One hypothesis suggests that bacteria
      from the genus Pseudonocardia are the sole, co-evolved mutualists of attine ants
      and are transmitted vertically by the queens. A recent study identified a
      Pseudonocardia-produced antifungal, named dentigerumycin, associated with the
      lower attine Apterostigma dentigerum consistent with the idea that co-evolved
      Pseudonocardia make novel antibiotics. An alternative possibility is that attine
      ants sample actinomycete bacteria from the soil, selecting and maintaining those
      species that make useful antibiotics. Consistent with this idea, a Streptomyces
      species associated with the higher attine Acromyrmex octospinosus was recently
      shown to produce the well-known antifungal candicidin. Candicidin production is
      widespread in environmental isolates of Streptomyces, so this could either be an
      environmental contaminant or evidence of recruitment of useful actinomycetes from
      the environment. It should be noted that the two possibilities for actinomycete
      acquisition are not necessarily mutually exclusive. RESULTS: In order to test
      these possibilities we isolated bacteria from a geographically distinct
      population of A. octospinosus and identified a candicidin-producing Streptomyces
      species, which suggests that they are common mutualists of attine ants, most
      probably recruited from the environment. We also identified a Pseudonocardia
      species in the same ant colony that produces an unusual polyene antifungal,
      providing evidence for co-evolution of Pseudonocardia with A. octospinosus.
      CONCLUSIONS: Our results show that a combination of co-evolution and
      environmental sampling results in the diversity of actinomycete symbionts and
      antibiotics associated with attine ants.

PMID- 20796278
TI  - GT-repeat polymorphism in the heme oxygenase-1 gene promoter and the risk of
      carotid atherosclerosis related to arsenic exposure.
AB  - BACKGROUND: Arsenic is a strong stimulus of heme oxygenase (HO)-1 expression in
      experimental studies in response to oxidative stress caused by a stimulus. A
      functional GT-repeat polymorphism in the HO-1 gene promoter was inversely
      correlated to the development of coronary artery disease in diabetics and
      development of restenosis following angioplasty in patients. The role of this
      potential vascular protective factor in carotid atherosclerosis remains unclear.
      We previously reported a graded association of arsenic exposure in drinking water
      with an increased risk of carotid atherosclerosis. In this study, we investigated
      the relationship between HO-1 genetic polymorphism and the risk of
      atherosclerosis related to arsenic. METHODS: Three-hundred and sixty-seven
      participants with an indication of carotid atherosclerosis and an additional 420
      participants without the indication, which served as the controls, from two
      arsenic exposure areas in Taiwan, a low arsenic-exposed Lanyang cohort and a high
      arsenic-exposed LMN cohort, were studied. Carotid atherosclerosis was evaluated
      using a duplex ultrasonographic assessment of the extracranial carotid arteries.
      Allelic variants of (GT)n repeats in the 5'-flanking region of the HO-1 gene were
      identified and grouped into a short (S) allele (< 27 repeats) and long (L) allele
      (>= 27 repeats). The association of atherosclerosis and the HO-1 genetic variants
      was assessed by a logistic regression analysis, adjusted for cardiovascular risk
      factors. RESULTS: Analysis results showed that arsenic's effect on carotid
      atherosclerosis differed between carriers of the class S allele (OR 1.39; 95% CI
      0.86-2.25; p = 0.181) and non-carriers (OR 2.65; 95% CI 1.03-6.82; p = 0.044) in
      the high-exposure LMN cohort. At arsenic exposure levels exceeding 750 MUg/L,
      difference in OR estimates between class S allele carriers and non-carriers was
      borderline significant (p = 0.051). In contrast, no such results were found in
      the low-exposure Lanyang cohort. CONCLUSIONS: This exploratory study suggests
      that at a relatively high level of arsenic exposure, carriers of the short (GT)n
      allele (< 27 repeats) in the HO-1 gene promoter had a lower probability of
      developing carotid atherosclerosis than non-carriers of the allele after long
      term arsenic exposure via ground water. The short (GT)n repeat in the HO-1 gene
      promoter may provide protective effects against carotid atherosclerosis in
      individuals with a high level of arsenic exposure.

PMID- 20796279
TI  - Mental disorder and caregiver burden in spouses: the Nord-Trondelag health study.
AB  - BACKGROUND: Researchers generally agree that mental disorder represents a burden
      to the family. The present study concerns the subjective burden of living with a
      person with mental disorder, more specifically the association between mental
      disorder in the index person and subjective well-being and symptoms of anxiety
      and depression in the spouse. METHODS: Data were obtained from questionnaires
      administered to the adult population of Nord-Trondelag County, Norway during the
      period 1995-1997. The present study is based on a subsample where 9,740 couples
      were identified. Subjective burden in spouses of persons with mental disorder was
      compared with subjective burden in spouses of persons without mental disorder,
      using analysis of variance (ANOVA). All analyses were stratified by sex. RESULTS:
      Adjusting for several covariates, spouses of persons with mental disorder scored
      significantly lower on subjective well-being and significantly higher on symptoms
      of anxiety and depression compared to spouses of index persons without mental
      disorder. Although highly significant, the effect sizes were moderate,
      corresponding to a difference in standard deviations ranging from .34 - .51.
      CONCLUSIONS: Our study supports the notion that there is an association between
      mental disorder in one partner and subjective burden in the spouse, but not to
      the same extent that have been reported in earlier studies, as our results do not
      indicate that a large proportion of the spouses reach a symptom level of anxiety
      and depression that reflects clinical mental disorder.

PMID- 20796281
TI  - Adenoid cystic carcinoma of the peripheral lung: a case report.
AB  - Adenoid cystic carcinoma of the peripheral lung is a rare entity. We recently
      encountered a patient with adenoid cystic carcinoma. A 75-year-old woman showed a
      nodular lesion with 10 mm in diameter in the right upper lung field on chest
      radiography. The diagnosis was unclear, but lung cancer could not be ruled out.
      Thoracoscopic biopsy was performed, and intraoperative pathological diagnosis
      revealed the carcinoma of the lung. We enforced upper lobectomy and mediastinal
      lymph node dissection to the patient. Histopathological examination revealed
      adenoid cystic carcinoma with a characteristic cribriform structure.
      Immunohistochemical examination revealed that the tumor cells were positive for
      thyroid transcription factor 1 (TTF-1), this tumor was diagnosed primary ACC of
      the lung.

PMID- 20796280
TI  - Autocrine regulation of human sperm motility by tachykinins.
AB  - BACKGROUND: We examined the presence and function of tachykinins and the
      tachykinin-degrading enzymes neprilysin (NEP) and neprilysin-2 (NEP2) in human
      spermatozoa. METHODS: Freshly ejaculated semen was collected from forty-eight
      normozoospermic human donors. We analyzed the expression of substance P,
      neurokinin A, neurokinin B, hemokinin-1, NEP and NEP2 in sperm cells by reverse
      transcriptase polymerase chain reaction (RT-PCR), western blot and
      immunocytochemistry assays and evaluated the effects of the neprilysin and
      neprilysin-2 inhibitor phosphoramidon on sperm motility in the absence and
      presence of tachykinin receptor-selective antagonists. Sperm motility was
      measured using WHO procedures or computer-assisted sperm analysis (CASA).
      RESULTS: The mRNAs of the genes that encode substance P/neurokinin A (TAC1),
      neurokinin B (TAC3), hemokinin-1 (TAC4), neprilysin (MME) and neprilysin-2
      (MMEL1) were expressed in human sperm. Immunocytochemistry studies revealed that
      tachykinin and neprilysin proteins were present in spermatozoa and show specific
      and differential distributions. Phosphoramidon increased sperm progressive
      motility and its effects were reduced in the presence of the tachykinin receptor
      antagonists SR140333 (NK1 receptor-selective) and SR48968 (NK2 receptor
      selective) but unmodified in the presence of SR142801 (NK3 receptor-selective).
      CONCLUSION: These data show that tachykinins are present in human spermatozoa and
      participate in the regulation of sperm motility. Tachykinin activity is
      regulated, at least in part, by neprilysins.

PMID- 20796282
TI  - Strand-specific RNA sequencing reveals extensive regulated long antisense
      transcripts that are conserved across yeast species.
AB  - BACKGROUND: Recent studies in budding yeast have shown that antisense
      transcription occurs at many loci. However, the functional role of antisense
      transcripts has been demonstrated only in a few cases and it has been suggested
      that most antisense transcripts may result from promiscuous bi-directional
      transcription in a dense genome. RESULTS: Here, we use strand-specific RNA
      sequencing to study anti-sense transcription in Saccharomyces cerevisiae. We
      detect 1,103 putative antisense transcripts expressed in mid-log phase growth,
      ranging from 39 short transcripts covering only the 3' UTR of sense genes to 145
      long transcripts covering the entire sense open reading frame. Many of these
      antisense transcripts overlap sense genes that are repressed in mid-log phase and
      are important in stationary phase, stress response, or meiosis. We validate the
      differential regulation of 67 antisense transcripts and their sense targets in
      relevant conditions, including nutrient limitation and environmental stresses.
      Moreover, we show that several antisense transcripts and, in some cases, their
      differential expression have been conserved across five species of yeast spanning
      150 million years of evolution. Divergence in the regulation of antisense
      transcripts to two respiratory genes coincides with the evolution of respiro
      fermentation. CONCLUSIONS: Our work provides support for a global and conserved
      role for antisense transcription in yeast gene regulation.

PMID- 20796283
TI  - The type IV pilin, PilA, is required for full virulence of Francisella tularensis
      subspecies tularensis.
AB  - BACKGROUND: All four Francisella tularensis subspecies possess gene clusters with
      potential to express type IV pili (Tfp). These clusters include putative pilin
      genes, as well as pilB, pilC and pilQ, required for secretion and assembly of
      Tfp. A hallmark of Tfp is the ability to retract the pilus upon surface contact,
      a property mediated by the ATPase PilT. Interestingly, out of the two major human
      pathogenic subspecies only the highly virulent type A strains have a functional
      pilT gene. RESULTS: In a previous study, we were able to show that one pilin
      gene, pilA, was essential for virulence of a type B strain in a mouse infection
      model. In this work we have examined the role of several Tfp genes in the
      virulence of the pathogenic type A strain SCHU S4. pilA, pilC, pilQ, and pilT
      were mutated by in-frame deletion mutagenesis. Interestingly, when mice were
      infected with a mixture of each mutant strain and the wild-type strain, the pilA,
      pilC and pilQ mutants were out-competed, while the pilT mutant was equally
      competitive as the wild-type. CONCLUSIONS: This suggests that expression and
      surface localisation of PilA contribute to virulence in the highly virulent type
      A strain, while PilT was dispensable for virulence in the mouse infection model.

PMID- 20796284
TI  - Food assistance is associated with improved body mass index, food security and
      attendance at clinic in an HIV program in central Haiti: a prospective
      observational cohort study.
AB  - BACKGROUND: Few data are available to guide programmatic solutions to the
      overlapping problems of undernutrition and HIV infection. We evaluated the impact
      of food assistance on patient outcomes in a comprehensive HIV program in central
      Haiti in a prospective observational cohort study. METHODS: Adults with HIV
      infection were eligible for monthly food rations if they had any one of:
      tuberculosis, body mass index (BMI) <18.5kg/m2, CD4 cell count <350/mm3 (in the
      prior 3 months) or severe socio-economic conditions. A total of 600 individuals
      (300 eligible and 300 ineligible for food assistance) were interviewed before
      rations were distributed, at 6 months and at 12 months. Data collected included
      demographics, BMI and food insecurity score (range 0 - 20). RESULTS: At 6- and 12
      month time-points, 488 and 340 subjects were eligible for analysis. Multivariable
      analysis demonstrated that at 6 months, food security significantly improved in
      those who received food assistance versus who did not (-3.55 vs -0.16; P <
      0.0001); BMI decreased significantly less in the food assistance group than in
      the non-food group (-0.20 vs -0.66; P = 0.020). At 12 months, food assistance was
      associated with improved food security (-3.49 vs -1.89, P = 0.011) and BMI (0.22
      vs -0.67, P = 0.036). Food assistance was associated with improved adherence to
      monthly clinic visits at both 6 (P < 0.001) and 12 months (P = 0.033).
      CONCLUSIONS: Food assistance was associated with improved food security,
      increased BMI, and improved adherence to clinic visits at 6 and 12 months among
      people living with HIV in Haiti and should be part of routine care where HIV and
      food insecurity overlap.

PMID- 20796285
TI  - Gene expression profiling in brain of mice exposed to the marine neurotoxin
      ciguatoxin reveals an acute anti-inflammatory, neuroprotective response.
AB  - BACKGROUND: Ciguatoxins (CTXs) are polyether marine neurotoxins and potent
      activators of voltage-gated sodium channels. This toxin is carried by multiple
      reef-fish species and human consumption of ciguatoxins can result in an explosive
      gastrointestinal/neurologic illness. This study characterizes the global
      transcriptional response in mouse brain to a symptomatic dose of the highly toxic
      Pacific ciguatoxin P-CTX-1 and additionally compares this data to transcriptional
      profiles from liver and whole blood examined previously. Adult male C57/BL6 mice
      were injected with 0.26 ng/g P-CTX-1 while controls received only vehicle.
      Animals were sacrificed at 1, 4 and 24 hrs and transcriptional profiling was
      performed on brain RNA with Agilent whole genome microarrays. RT-PCR was used to
      independently validate gene expression and the web tool DAVID was used to analyze
      gene ontology (GO) and molecular pathway enrichment of the gene expression data.
      RESULTS: A pronounced 4 degrees C hypothermic response was recorded in these
      mice, reaching a minimum at 1 hr and lasting for 8 hrs post toxin exposure. Ratio
      expression data were filtered by intensity, fold change and p-value, with the
      resulting data used for time course analysis, K-means clustering, ontology
      classification and KEGG pathway enrichment. Top GO hits for this gene set
      included acute phase response and mono-oxygenase activity. Molecular pathway
      analysis showed enrichment for complement/coagulation cascades and metabolism of
      xenobiotics. Many immediate early genes such as Fos, Jun and Early Growth
      Response isoforms were down-regulated although others associated with stress such
      as glucocorticoid responsive genes were up-regulated. Real time PCR confirmation
      was performed on 22 differentially expressed genes with a correlation of 0.9
      (Spearman's Rho, p < 0.0001) with microarray results. CONCLUSIONS: Many of the
      genes differentially expressed in this study, in parallel with the hypothermia,
      figure prominently in protection against neuroinflammation. Pathologic activity
      of the complement/coagulation cascade has been shown in patients suffering from a
      chronic form of ciguatera poisoning and is of particular interest in this model.
      Anti-inflammatory processes were at work not only in the brain but were also seen
      in whole blood and liver of these animals, creating a systemic anti-inflammatory
      environment to protect against the initial cellular damage caused by the toxin.

PMID- 20796286
TI  - Predictive equations over-estimate the resting energy expenditure in amyotrophic
      lateral sclerosis patients who are dependent on invasive ventilation support.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a form of degenerative motor
      neuron disease. At the end stage of the disease artificial feeding is often
      required. Nevertheless, very little is known about the energy demand of those ALS
      patients who are chronically dependent on tracheostomy intermittent positive
      pressure ventilation. The objective of our study was to clarify the resting
      energy expenditure (REE) in mechanically ventilated ALS patients. METHODS: We
      measured the REE of five ALS patients (four men, one female) twice during a 12
      month-period using indirect calorimetry with two sampling flow settings (40 L/min
      and 80 L/min). The measured REEs (mREE) were compared with values calculated
      using five different predictive equations. RESULTS: The mean (+/- SD) of all
      mREEs was 1130 +/- 170 kcal/d. The measurements with different flow settings and
      at different time instances provided similar results. The mean of mREEs was 33.6%
      lower, as compared to the mean calculated with five different predictive
      equations REE (p < 0.001). Each of the predictive equations over-estimated the
      REE. CONCLUSIONS: The mREE values were significantly lower for every patient than
      all the predicted ones. Determination of daily nutrition with predictive
      equations may therefore lead in mis-estimation of energy requirements. Because
      ALS patients may live years with artificial ventilation their nutritional support
      should be based on individual measurements. However, further study is needed due
      to the small number of subjects.

PMID- 20796287
TI  - Transpositional reactivation of the Dart transposon family in rice lines derived
      from introgressive hybridization with Zizania latifolia.
AB  - BACKGROUND: It is widely recognized that interspecific hybridization may induce
      "genome shock", and lead to genetic and epigenetic instabilities in the resultant
      hybrids and/or backcrossed introgressants. A prominent component involved in the
      genome shock is reactivation of cryptic transposable elements (TEs) in the hybrid
      genome, which is often associated with alteration in the elements' epigenetic
      modifications like cytosine DNA methylation. We have previously reported that
      introgressants derived from hybridization between Oryza sativa (rice) and Zizania
      latifolia manifested substantial methylation re-patterning and rampant
      mobilization of two TEs, a copia retrotransposon Tos17 and a MITE mPing. It was
      not known however whether other types of TEs had also been transpositionally
      reactivated in these introgressants, their relevance to alteration in cytosine
      methylation, and their impact on expression of adjacent cellular genes. RESULTS:
      We document in this study that the Dart TE family was transpositionally
      reactivated followed by stabilization in all three studied introgressants (RZ1,
      RZ2 and RZ35) derived from introgressive hybridization between rice (cv.
      Matsumae) and Z. latifolia, while the TEs remained quiescent in the recipient
      rice genome. Transposon-display (TD) and sequencing verified the element's
      mobility and mapped the excisions and re-insertions to the rice chromosomes.
      Methylation-sensitive Southern blotting showed that the Dart TEs were heavily
      methylated along their entire length, and moderate alteration in cytosine
      methylation patterns occurred in the introgressants relative to their rice
      parental line. Real-time qRT-PCR quantification on the relative transcript
      abundance of six single-copy genes flanking the newly excised or inserted Dart
      related TE copies indicated that whereas marked difference in the expression of
      all four genes in both tissues (leaf and root) were detected between the
      introgressants and their rice parental line under both normal and various stress
      conditions, the difference showed little association with the presence or absence
      of the newly mobilized Dart-related TEs. CONCLUSION: Introgressive hybridization
      has induced transpositional reactivation of the otherwise immobile Dart-related
      TEs in the parental rice line (cv. Matsumae), which was accompanied with a
      moderate alteration in the element's cytosine methylation. Significant difference
      in expression of the Dart-adjacent genes occurred between the introgressants and
      their rice parental line under both normal and various abiotic stress conditions,
      but the alteration in gene expression was not coupled with the TEs.

PMID- 20796288
TI  - Hydric stress-dependent effects of Plasmodium falciparum infection on the
      survival of wild-caught Anopheles gambiae female mosquitoes.
AB  - BACKGROUND: Whether Plasmodium falciparum, the agent of human malaria responsible
      for over a million deaths per year, causes fitness costs in its mosquito vectors
      is a burning question that has not yet been adequately resolved. Understanding
      the evolutionary forces responsible for the maintenance of susceptibility and
      refractory alleles in natural mosquito populations is critical for understanding
      malaria transmission dynamics. METHODS: In natural mosquito populations,
      Plasmodium fitness costs may only be expressed in combination with other
      environmental stress factors hence this hypothesis was tested experimentally.
      Wild-caught blood-fed Anopheles gambiae s.s. females of the M and S molecular
      form from an area endemic for malaria in Mali, West Africa, were brought to the
      laboratory and submitted to a 7-day period of mild hydric stress or kept with
      water ad-libitum. At the end of this experiment all females were submitted to
      intense desiccation until death. The survival of all females throughout both
      stress episodes, as well as their body size and infection status was recorded.
      The importance of stress, body size and molecular form on infection prevalence
      and female survival was investigated using Logistic Regression and Proportional
      Hazard analysis. RESULTS: Females subjected to mild stress exhibited patterns of
      survival and prevalence of infection compatible with increased parasite-induced
      mortality compared to non-stressed females. Fitness costs seemed to be linked to
      ookinetes and early oocyst development but not the presence of sporozoites. In
      addition, when females were subjected to intense desiccation stress, those
      carrying oocysts exhibited drastically reduced survival but those carrying
      sporozoites were unaffected. No significant differences in prevalence of
      infection and infection-induced mortality were found between the M and S
      molecular forms of Anopheles gambiae. CONCLUSIONS: Because these results suggest
      that infected mosquitoes may incur fitness costs under natural-like conditions,
      they are particularly relevant to vector control strategies aiming at boosting
      naturally occurring refractoriness or spreading natural or foreign genes for
      refractoriness using genetic drive systems in vector populations.

PMID- 20796289
TI  - The power to detect artificial selection acting on single loci in recently
      domesticated species.
AB  - BACKGROUND: An increasing number of aquaculture species are subjected to
      artificial selection in systematic breeding programs. Rapid improvements of
      important commercial traits are reported, but little is known about the effects
      of the strong directional selection applied, on gene level variation. Large
      numbers of genetic markers are becoming available, making it feasible to detect
      and estimate these effects. Here a simulation tool was developed in order to
      explore the power by which single genetic loci subjected to uni-directional
      selection in parallel breeding populations may be detected. FINDINGS: Two
      simulation models were pursued: 1) screening for loci displaying higher genetic
      differentiation than expected (high-FST outliers), from neutral evolution between
      a pool of domesticated populations and a pool of wild populations; 2) screening
      for loci displaying lower genetic differentiation (low-FST outliers) between
      domesticated strains than expected from neutral evolution. The premise for both
      approaches was that the isolated domesticated strains are subjected to the same
      breeding goals. The power to detect outlier loci was calculated under the
      following parameter values: number of populations, effective population size per
      population, number of generations since onset of selection, initial FST, and the
      selection coefficient acting on the locus. Among the parameters investigated,
      selection coefficient, the number of generation since onset of selection, and
      number of populations, had the largest impact on power. The power to detect loci
      subjected to directional in breeding programmes was high when applying the
      between farmed and wild population approach, and low for the between farmed
      populations approach. CONCLUSIONS: A simulation tool was developed for estimating
      the power to detect artificial selection acting directly on single loci. The
      simulation tool should be applicable to most species subject to domestication, as
      long as a reasonable high accuracy in input parameters such as effective
      population size, number of generations since the initiation of selection, and
      initial differentiation (FST) can be obtained. Identification of genetic loci
      under artificial selection would be highly valuable, since such loci could be
      used to monitor maintenance of genetic variation in the breeding populations and
      monitoring possible genetic changes in wild populations from genetic interaction
      between escapees and their wild counterpart.

PMID- 20796290
TI  - Involvement of TIP60 acetyltransferase in intracellular Salmonella replication.
AB  - BACKGROUND: Salmonella enterica is a facultative intracellular pathogen that
      replicates within a membrane-bound compartment termed Salmonella containing
      vacuole (SCV). The biogenesis of SCV requires Salmonella type III protein
      secretion/translocation system and their effector proteins which are translocated
      into host cells to exploit the vesicle trafficking pathways. SseF is one of these
      effectors required for SCV formation and Intracellular Salmonella replication
      through unknown mechanisms. RESULTS: In an attempt to identify host proteins that
      interact with SseF, we conduct a yeast two-hybrid screening of human cell cDNA
      library using SseF as the bait. We identified that TIP60, an acetyltransferase,
      interacts with SseF. We showed that the TIP60 acetylation activity was increased
      in the presence of SseF, and TIP60 was upregulated upon Salmonella infection. In
      addition, TIP60 is required for efficient intracellular Salmonella replication in
      macrophages. CONCLUSION: Taken together, our data suggest that Salmonella may use
      SseF to exploit the host TIP60 acetyltransferase activity to promote efficient
      Salmonella replication inside host cells.

PMID- 20796291
TI  - Basic mechanisms of arsenic trioxide (ATO)-induced apoptosis in human leukemia
      (HL-60) cells.
AB  - BACKGROUND: Acute promyelocytic leukemia (APL) is a blood cancer that affects
      people of all ages and strikes about 1,500 patients in the United States each
      year. The standard treatment of APL has been based on the combined administration
      of all-trans retinoic acid and chemotherapy including anthracyclins and
      cytarabine. However, 10-20% of patients relapse, with their disease becoming
      resistant to conventional treatment. Recently the Food and Drug Administration
      has approved the use of arsenic trioxide (ATO) or Trisenox for the treatment of
      APL, based on clinical studies showing a complete remission, especially in
      relapsed patients. In a recently published study we demonstrated that ATO
      pharmacology as an anti-cancer drug is associated with its cytotoxic and
      genotoxic effects in human leukemia cells. METHODS: In the present study, we
      further investigated the apoptotic mechanisms of ATO toxicity using the HL-60
      cell line as a test model. Apoptosis was measured by flow cytometry analysis of
      phosphatidylserine externalization (Annexin V assay) and caspase 3 activity, and
      by DNA laddering assay. RESULTS: Flow cytometry data showed a strong dose
      response relationship between ATO exposure and Annexin-V positive HL-60 cells.
      Similarly, a statistically significant and dose-dependent increase (p <0.05) was
      recorded with regard to caspase 3 activity in HL60 cells undergoing late
      apoptosis. These results were confirmed by data of DNA laddering assay showing a
      clear evidence of nucleosomal DNA fragmentation in ATO-treated cells. CONCLUSION:
      Taken together, our research demonstrated that ATO represents an apoptosis
      inducing agent and its apoptotic mechanisms involve phosphatidylserine
      externalization, caspase 3 activation and nucleosomal DNA fragmentation.

PMID- 20796292
TI  - Domestic water carrying and its implications for health: a review and mixed
      methods pilot study in Limpopo Province, South Africa.
AB  - BACKGROUND: Lack of access to safe water remains a significant risk factor for
      poor health in developing countries. There has been little research into the
      health effects of frequently carrying containers of water. The aims of this study
      were to better understand how domestic water carrying is performed, identify
      potential health risk factors and gain insight into the possible health effects
      of the task. METHODS: Mixed methods of data collection from six were used to
      explore water carrying performed by people in six rural villages of Limpopo
      Province, South Africa. Data was collected through semi-structured interviews and
      through observation and measurement. Linear regression modelling were used to
      identify significant correlations between potential risk factors and rating of
      perceived exertion (RPE) or self reported pain. Independent t-tests were used to
      compare the mean values of potential risk factors and RPE between sub-groups
      reporting pain and those not reporting pain. RESULTS: Water carrying was mainly
      performed by women or children carrying containers on their head (mean container
      weight 19.5 kg) over a mean distance of 337 m. The prevalence of spinal (neck or
      back) pain was 69% and back pain was 38%. Of participants who carried water by
      head loading, the distance walked by those who reported spinal pain was
      significantly less than those who did not (173 m 95%CI 2-343; p = 0.048). For
      head loaders reporting head or neck pain compared to those who did not, the
      differences in weight of water carried (4.6 kg 95%CI -9.7-0.5; p = 0.069) and RPE
      (2.5 95%CI -5.1-0.1; p = 0.051) were borderline statistically significant. For
      head loaders, RPE was significantly correlated with container weight (r = 0.52; p
      = 0.011) and incline (r = 0.459; p = 0.018) CONCLUSIONS: Typical water carrying
      methods impose physical loading with potential to produce musculoskeletal
      disorders and related disability. This exploratory study is limited by a small
      sample size and future research should aim to better understand the type and
      strength of association between water carrying and health, particularly
      musculoskeletal disorders. However, these preliminary findings suggest that
      efforts should be directed toward eliminating the need for water carrying, or
      where it must continue, identifying and reducing risk factors for musculoskeletal
      disorders and physical injury.

PMID- 20796293
TI  - Single locus affects embryonic segment polarity and multiple aspects of an adult
      evolutionary novelty.
AB  - BACKGROUND: The characterization of the molecular changes that underlie the
      origin and diversification of morphological novelties is a key challenge in
      evolutionary developmental biology. The evolution of such traits is thought to
      rely largely on co-option of a toolkit of conserved developmental genes that
      typically perform multiple functions. Mutations that affect both a universal
      developmental process and the formation of a novelty might shed light onto the
      genetics of traits not represented in model systems. Here we describe three
      pleiotropic mutations with large effects on a novel trait, butterfly eyespots,
      and on a conserved stage of embryogenesis, segment polarity. RESULTS: We show
      that three mutations affecting eyespot size and/or colour composition in Bicyclus
      anynana butterflies occurred in the same locus, and that two of them are
      embryonic recessive lethal. Using surgical manipulations and analysis of gene
      expression patterns in developing wings, we demonstrate that the effects on
      eyespot morphology are due to changes in the epidermal response component of
      eyespot induction. Our analysis of morphology and of gene expression in mutant
      embryos shows that they have a typical segment polarity phenotype, consistent
      with the mutant locus encoding a negative regulator of Wingless signalling.
      CONCLUSIONS: This study characterizes the segregation and developmental effects
      of alleles at a single locus that controls the morphology of a lineage-specific
      trait (butterfly eyespots) and a conserved process (embryonic segment polarity
      and, specifically, the regulation of Wingless signalling). Because no gene with
      such function was found in the orthologous, highly syntenic genomic regions of
      two other lepidopterans, we hypothesize that our locus is a yet undescribed,
      possibly lineage-specific, negative regulator of the conserved Wnt/Wg pathway.
      Moreover, the fact that this locus interferes with multiple aspects of eyespot
      morphology and maps to a genomic region containing key wing pattern loci in
      different other butterfly species suggests it might correspond to a 'hotspot'
      locus in the diversification of this novel trait.

PMID- 20796294
TI  - The utility of superficial abdominal reflex in the initial diagnosis of
      scoliosis: a retrospective review of clinical characteristics of scoliosis with
      syringomyelia.
AB  - BACKGROUND: With increasing use of magnetic resonance imaging (MRI), underlying
      syringomyelia is increasingly found in patients with presumed idiopathic
      scoliosis. To determine the indications for MRI in the differential diagnosis of
      scoliosis, several clinical characteristics of syringomyelia have been reported.
      Neurological signs, particularly abnormal superficial abdominal reflex (SAR), are
      important in establishing the initial diagnosis of scoliosis. However, the
      prevalence of abnormal SAR in patients with scoliosis and the sensitivity of this
      sign in predicting syringomyelia are not well known. We aimed to determine the
      diagnostic utility of SAR and other characteristics of syringomyelia in patients
      with scoliosis. METHODS: We reviewed the medical records of 93 patients with
      scoliosis, 90 of whom underwent corrective surgery. All patients underwent MRI to
      determine the presence of syringomyelia. Mean age at surgery was 12.5 years.
      Abnormal SAR was defined as unilateral or bilateral absence or hyporeflexia of
      SAR. We calculated indices of diagnostic utility of abnormal SAR for non
      idiopathic scoliosis and for syringomyelia. Abnormal SAR, left thoracic curve
      pattern, gender, and curve flexibility were compared between scoliosis with
      syringomyelia and idiopathic scoliosis. Logistic regression analysis was
      performed with the existence of syringomyelia as the dependent variable and curve
      flexibility as the independent variable. RESULTS: Abnormal SAR was observed in 20
      patients (prevalence 22%). All 6 patients with myopathic scoliosis displayed
      bilateral absence of SAR. The sensitivity of abnormal SAR for non-idiopathic
      scoliosis was 38%, with 96% specificity, 90% PPV (positive predictive value), and
      60% NPV (negative predictive value). Syringomyelia was identified in 9 of the 93
      patients (9.7%); 8 of these had abnormal SAR. The sensitivity of abnormal SAR for
      syringomyelia in presumed idiopathic scoliosis was 89%, with 95% specificity, 80%
      PPV, and 98% NPV. Gender, abnormal neurological findings, and curve flexibility
      differed significantly between patients with syringomyelia and those with
      idiopathic scoliosis (P < 0.05). In the logistic regression model, the area under
      the receiver operating characteristic (ROC) curve was 0.79 and the cut-off value
      of curve flexibility for syringomyelia was 50% (P = 0.08). CONCLUSION: Abnormal
      SAR was a useful indicator not only for syringomyelia, but also for myogenic
      scoliosis.

PMID- 20796295
TI  - Oral intake of Lactobacillus pentosus strain b240 accelerates salivary
      immunoglobulin A secretion in the elderly: A randomized, placebo-controlled,
      double-blind trial.
AB  - BACKGROUND: Immunoglobulin A (IgA) secretion in saliva decreases with age and may
      be the cause of increased vulnerability of the elderly to respiratory infections.
      The effect of oral intake of lactic acid bacteria on salivary secretory IgA
      (SIgA) in the elderly has not been reported. The objective of this study was to
      demonstrate the acceleration of salivary SIgA secretion by oral intake of
      Lactobacillus pentosus strain b240 (b240) in the elderly. RESULTS: A total of 80
      healthy elderly individuals were randomly allocated to either an intervention
      (i.e., b240) or a control (i.e., placebo) group. The elderly individuals in the
      b240 group were given a sterile water beverage (125 mL) containing heat-killed
      b240 (4 * 109 cells), while those in the placebo group were given only a sterile
      water beverage (125 mL); both groups received their respective beverages once
      daily for 12 weeks. Saliva was collected before initiation of the study and every
      2 weeks thereafter. Saliva flow rate and SIgA concentration were determined, and
      the SIgA secretion rate was calculated. The mean salivary SIgA secretion rate in
      the b240 group steadily increased until week 4 (exhibiting a 20% elevation
      relative to that at week 0), and then remained stable until week 12. Changes in
      SIgA secretion rate over the intervention period were significantly greater in
      the b240 group than in the placebo group. The treatment groups exhibited no
      significant differences in adverse events. CONCLUSIONS: Oral intake of L.
      pentosus strain b240 for 12 weeks significantly accelerated salivary SIgA
      secretion, thereby indicating its potential utility in the improvement of mucosal
      immunity and resistance against infection in the elderly.

PMID- 20796296
TI  - Author's response to Poole, C. Commentary: How Many Are Affected? A Real Limit of
      Epidemiology.

PMID- 20796297
TI  - Interpretation of evidence in data by untrained medical students: a scenario
      based study.
AB  - BACKGROUND: To determine which approach to assessment of evidence in data -
      statistical tests or likelihood ratios - comes closest to the interpretation of
      evidence by untrained medical students. METHODS: Empirical study of medical
      students (N = 842), untrained in statistical inference or in the interpretation
      of diagnostic tests. They were asked to interpret a hypothetical diagnostic test,
      presented in four versions that differed in the distributions of test scores in
      diseased and non-diseased populations. Each student received only one version.
      The intuitive application of the statistical test approach would lead to
      rejecting the null hypothesis of no disease in version A, and to accepting the
      null in version B. Application of the likelihood ratio approach led to opposite
      conclusions - against the disease in A, and in favour of disease in B. Version C
      tested the importance of the p-value (A: 0.04 versus C: 0.08) and version D the
      importance of the likelihood ratio (C: 1/4 versus D: 1/8). RESULTS: In version A,
      7.5% concluded that the result was in favour of disease (compatible with p
      value), 43.6% ruled against the disease (compatible with likelihood ratio), and
      48.9% were undecided. In version B, 69.0% were in favour of disease (compatible
      with likelihood ratio), 4.5% against (compatible with p value), and 26.5%
      undecided. Increasing the p value from 0.04 to 0.08 did not change the results.
      The change in the likelihood ratio from 1/4 to 1/8 increased the proportion of
      non-committed responses. CONCLUSIONS: Most untrained medical students appear to
      interpret evidence from data in a manner that is compatible with the use of
      likelihood ratios.

PMID- 20796298
TI  - Transverse plane pelvic rotation increase (TPPRI) following rotationally
      corrective instrumentation of adolescent idiopathic scoliosis double curves.
AB  - BACKGROUND: We have occasionally observed clinically noticeable postoperative
      transverse plane pelvic rotation increase (TPPRI) in the direction of direct
      thoracolumbar/lumbar rotational corrective load applied during posterior
      instrumentation and arthrodesis for double (Lenke 3 and 6) adolescent idiopathic
      scoliosis (AIS) curves. Our purposes were to document this occurrence; identify
      its frequency, associated variables, and natural history; and determine its
      effect upon patient outcome. METHODS: Transverse plane pelvic rotation (TPPR) can
      be quantified using the left/right hemipelvis width ratio as measured on standing
      posterior-anterior scoliosis radiographs. Descriptive statistics were done to
      determine means and standard deviations. Non-parametric statistical tests were
      used due to the small sample size and non-normally distributed data. Significance
      was set at P < 0.05. RESULTS: Seventeen of 21 (81%) consecutive patients with
      double curves (7 with Lenke 3 curves and 10 with Lenke 6) instrumented with
      lumbar pedicle screw anchors to achieve direct rotation had a complete sequence
      of measurable radiographs. While 10 of these 17 had no postoperative TPPRI, 7 did
      all in the direction of the rotationally corrective thoracolumbar instrumentation
      load. Two preoperative variables were associated with postoperative TPPRI: more
      tilt of the vertebra below the lower instrumented vertebra (-23 degrees  +/- 3.1
      degrees  vs. -29 degrees  +/- 4.6 degrees , P = 0.014) and concurrent anterior
      thoracolumbar discectomy and arthrodesis (5 of 10 vs. 7 of 7, P = 0.044).
      Patients with a larger thoracolumbar/lumbar angle of trunk inclination or larger
      lower instrumented vertebra plus one to sacrum fractional/hemicurve were more
      likely to have received additional anterior thoracolumbar discectomy and
      arthrodesis (c = 0.90 and c = 0.833, respectively).Postoperative TPPRI resolved
      in 5 of the 7 by intermediate follow-up at 12 months. Patient outcome was not
      adversely affected by postoperative TPPRI, whether or not it persisted.
      CONCLUSIONS: Our findings suggest that TPPRI is a decompensation caused by
      extension of the corrective thoracolumbar rotational load into the lumbosacral
      hemicurve below. As posterior instrumentation of adolescent idiopathic scoliosis
      becomes increasingly more effective in the transverse plane, postoperative TPPRI
      may become more widely noticed. This study provides some assurance that
      recompensation usually occurs, but that in either event TPPRI does not seem to
      affect clinical outcome.

PMID- 20796299
TI  - Coherent pipeline for biomarker discovery using mass spectrometry and
      bioinformatics.
AB  - BACKGROUND: Robust biomarkers are needed to improve microbial identification and
      diagnostics. Proteomics methods based on mass spectrometry can be used for the
      discovery of novel biomarkers through their high sensitivity and specificity.
      However, there has been a lack of a coherent pipeline connecting biomarker
      discovery with established approaches for evaluation and validation. We propose
      such a pipeline that uses in silico methods for refined biomarker discovery and
      confirmation. RESULTS: The pipeline has four main stages: Sample preparation,
      mass spectrometry analysis, database searching and biomarker validation. Using
      the pathogen Clostridium botulinum as a model, we show that the robustness of
      candidate biomarkers increases with each stage of the pipeline. This is enhanced
      by the concordance shown between various database search algorithms for peptide
      identification. Further validation was done by focusing on the peptides that are
      unique to C. botulinum strains and absent in phylogenetically related Clostridium
      species. From a list of 143 peptides, 8 candidate biomarkers were reliably
      identified as conserved across C. botulinum strains. To avoid discarding other
      unique peptides, a confidence scale has been implemented in the pipeline giving
      priority to unique peptides that are identified by a union of algorithms.
      CONCLUSIONS: This study demonstrates that implementing a coherent pipeline which
      includes intensive bioinformatics validation steps is vital for discovery of
      robust biomarkers. It also emphasises the importance of proteomics based methods
      in biomarker discovery.

PMID- 20796300
TI  - Circulating mediators of bone remodeling in psoriatic arthritis: implications for
      disordered osteoclastogenesis and bone erosion.
AB  - INTRODUCTION: Diverse bone pathologies are observed in patients with psoriatic
      arthritis (PsA). Uncoupling of bone remodeling with disordered osteoclastogenesis
      has been implicated in the pathogenesis of PsA. The aim of this study was to
      examine the role of soluble mediators of bone remodeling within the circulation
      of patients with PsA. METHODS: Patients with PsA (n = 38), with psoriasis (n =
      10), and healthy controls (n = 12) were studied. Serum was obtained for testing
      of Dikkopf-1 (Dkk-1), macrophage-colony stimulating factor (M-CSF),
      osteoprotegerin (OPG), and receptor activator of nuclear factor-kappaB ligand
      (RANKL) with ELISA. Patients with PsA also had bone densitometry, plain
      radiographs of the hands and feet, and assessment of peripheral blood osteoclast
      precursors. Radiographs were scored for erosion, joint-space narrowing,
      osteolysis, and new bone formation. RESULTS: Compared with those with psoriasis
      and healthy controls, patients with PsA had higher circulating concentrations of
      Dkk-1 and M-CSF. In patients with PsA, M-CSF and RANKL, but not Dkk-1,
      concentrations positively correlated with radiographic erosion, joint-space
      narrowing, and osteolysis scores. Mediators of bone remodeling did not correlate
      with the number of joints with new bone formation or with total hip-bone mineral
      density. Peripheral blood CD14+/CD11b+ cells, and the number of osteoclast-like
      cells and resorptive pits after culture with RANKL and M-CSF also correlated with
      radiographic damage scores. Circulating M-CSF concentrations correlated with the
      percentage of peripheral blood CD14+/CD11b+ cells. CONCLUSIONS: Systemic
      expression of soluble factors that promote osteoclastogenesis is disordered in
      patients with PsA and may contribute to periarticular bone loss in this disease.

PMID- 20796301
TI  - Review of Alzheimer's disease scales: is there a need for a new multi-domain
      scale for therapy evaluation in medical practice?
AB  - INTRODUCTION: The present review of Alzheimer's disease (AD) rating scales aims
      to outline the need for a new rating scale to be used in routine clinical
      practice for long-term medical care of AD patients. An ideal scale would be: 1)
      practical, easy and quick to administer for an experienced clinician; 2)
      validated for AD; 3) multi-domain: covering the AD-relevant areas of cognition,
      activities of daily living, behavior, communication/social interaction, and
      quality of life; 4) applicable to all AD severity stages; 5) able to monitor
      disease progression; and 6) sensitive to measure therapy effects. METHODS: The
      National Library of Medicines' MEDLINE database was searched for the years 1981
      to September 2008, using a set of keywords aiming to select instruments which
      cover at least some of the requirements for an ideal practical AD scale for
      therapy evaluation. Measures for AD staging and screening tests were not
      considered for review. RESULTS: Of 1,902 articles resulting from the literature
      search, 68 relevant AD scales were identified. Most of them were scales that
      predominantly measure the severity of major dysfunctions in particular AD
      domains. Only five scales met some of the requirements for a practical multi
      domain AD scale, but did not possess all required characteristics. CONCLUSIONS:
      Despite the multitude of AD scales for various purposes, there remains a need for
      a new multi-domain and easy to administer AD scale for assessment of disease
      progression and response to therapy in daily medical practice.

PMID- 20796302
TI  - Multiplicity of Plasmodium falciparum infection following intermittent preventive
      treatment in infants.
AB  - BACKGROUND: Intermittent preventive treatment in infants with sulphadoxine
      pyrimethamine (IPTi-SP) reduces malaria morbidity by 20% to 33%. Potentially,
      however, this intervention may compromise the acquisition of immunity, including
      the tolerance towards multiple infections with Plasmodium falciparum. METHODS:
      Plasmodium falciparum isolates were obtained from children participating in two
      Ghanaian IPTi-SP trials (Tamale, Afigya Sekyere) at 15 months of age, i.e., six
      months after they had received the second dose of IPTi-SP or placebo. By typing
      the polymorphic merozoite surface protein 1 (msp1) and msp2 genes, multiplicity
      of infection (MOI) was assessed in 389 isolates. A total of additional 133
      samples were collected in Tamale at 3, 6, 9, and 12 months of age. Comparisons of
      MOI between groups were done by non-parametric statistical tests. RESULTS: The
      number of distinguishable P. falciparum clones (MOI) ranged between one and six.
      Mean MOI in Tamale was stable at 2.13 - 2.17 during the first year of life, and
      increased to 2.57 at age 15 months (P = 0.01). At no age did MOI differ between
      the IPTi-SP and placebo groups (each, P >= 0.5). At 15 months of age, i.e., six
      months after the second dose, MOI was very similar for children who had received
      IPTi or placebo (means, 2.25 vs. 2.33; P = 0.55) as was the proportion of
      polyclonal infections (69.6% vs. 69.7%; P = 0.99). Adjusting for study site,
      current and prior malaria, parasite density, and season did not change this
      finding. CONCLUSIONS: IPTi-SP appears to have no impact on the multiplicity of
      infection during infancy and thereafter. This suggests that tolerance of multiple
      infections, a component of protective immunity in highly endemic areas, is not
      affected by this intervention.

PMID- 20796303
TI  - An investigation of intensity-modulated radiation therapy versus conventional two
      dimensional and 3D-conformal radiation therapy for early stage larynx cancer.
AB  - INTRODUCTION: Intensity modulated radiation therapy (IMRT) has been incorporated
      at several institutions for early stage laryngeal cancer (T1/T2N0M0), but its
      utility is controversial. METHODS: In three representative patients, multiple
      plans were generated: 1) Conventional 2D planning, with the posterior border
      placed at either the anterior aspect ("tight" plan) or the mid-vertebral body
      ("loose" plan), 2) 3D planning, utilizing both 1.0 and 0.5 cm margins for the
      planning target volume (PTV), and 3) IMRT planning, utilizing the same margins as
      the 3D plans. A dosimetric comparison was performed for the target volume, spinal
      cord, arytenoids, and carotid arteries. The prescription dose was 6300 cGy (225
      cGy fractions), and the 3D and IMRT plans were normalized to this dose. RESULTS:
      For PTV margins of 1.0 cm and 0.5 cm, the D95 of the 2D tight/loose plans were
      3781/5437 cGy and 5372/5869 cGy, respectively (IMRT/3D plans both 6300 cGy). With
      a PTV margin of 1.0 cm, the mean carotid artery dose was 2483/5671/5777/4049 cGy
      in the 2D tight, 2D loose, 3D, and IMRT plans, respectively. When the PTV was
      reduced to 0.5 cm, the the mean carotid artery dose was 2483/5671/6466/2577 cGy
      to the above four plans, respectively. The arytenoid doses were similar between
      the four plans, and spinal cord doses were well below tolerance. CONCLUSIONS:
      IMRT provides a more ideal dose distribution compared to 2D treatment and 3D
      planning in regards to mean carotid dose. We therefore recommend IMRT in select
      cases when the treating physician is confident with the GTV.

PMID- 20796304
TI  - Surface EMG pattern recognition for real-time control of a wrist exoskeleton.
AB  - BACKGROUND: Surface electromyography (sEMG) signals have been used in numerous
      studies for the classification of hand gestures and movements and successfully
      implemented in the position control of different prosthetic hands for amputees.
      sEMG could also potentially be used for controlling wearable devices which could
      assist persons with reduced muscle mass, such as those suffering from sarcopenia.
      While using sEMG for position control, estimation of the intended torque of the
      user could also provide sufficient information for an effective force control of
      the hand prosthesis or assistive device. This paper presents the use of pattern
      recognition to estimate the torque applied by a human wrist and its real-time
      implementation to control a novel two degree of freedom wrist exoskeleton
      prototype (WEP), which was specifically developed for this work. METHODS: Both
      sEMG data from four muscles of the forearm and wrist torque were collected from
      eight volunteers by using a custom-made testing rig. The features that were
      extracted from the sEMG signals included root mean square (rms) EMG amplitude,
      autoregressive (AR) model coefficients and waveform length. Support Vector
      Machines (SVM) was employed to extract classes of different force intensity from
      the sEMG signals. After assessing the off-line performance of the used
      classification technique, the WEP was used to validate in real-time the proposed
      classification scheme. RESULTS: The data gathered from the volunteers were
      divided into two sets, one with nineteen classes and the second with thirteen
      classes. Each set of data was further divided into training and testing data. It
      was observed that the average testing accuracy in the case of nineteen classes
      was about 88% whereas the average accuracy in the case of thirteen classes
      reached about 96%. Classification and control algorithm implemented in the WEP
      was executed in less than 125 ms. CONCLUSIONS: The results of this study showed
      that classification of EMG signals by separating different levels of torque is
      possible for wrist motion and the use of only four EMG channels is suitable. The
      study also showed that SVM classification technique is suitable for real-time
      classification of sEMG signals and can be effectively implemented for controlling
      an exoskeleton device for assisting the wrist.

PMID- 20796305
TI  - A standard variation file format for human genome sequences.
AB  - Here we describe the Genome Variation Format (GVF) and the 10Gen dataset. GVF, an
      extension of Generic Feature Format version 3 (GFF3), is a simple tab-delimited
      format for DNA variant files, which uses Sequence Ontology to describe genome
      variation data. The 10Gen dataset, ten human genomes in GVF format, is freely
      available for community analysis from the Sequence Ontology website and from an
      Amazon elastic block storage (EBS) snapshot for use in Amazon's EC2 cloud
      computing environment.

PMID- 20796306
TI  - Overview of the Canadian pediatric end-stage renal disease database.
AB  - BACKGROUND: Performing clinical research among pediatric end-stage renal disease
      patients is challenging. Barriers to successful initiation and completion of
      clinical research projects include small sample sizes and resultant limited
      statistical power and lack of longitudinal follow-up for hard clinical end-points
      in most single center studies. DESCRIPTION: Existing longitudinal organ failure
      disease registry and administrative health datasets available within a universal
      access health care system can be used to study outcomes of end-stage renal
      disease among pediatric patients in Canada. To construct the Canadian Pediatric
      End-Stage Renal Disease database, registry data were linked to administrative
      health data through deterministic linkage techniques creating a research database
      which consists of socio-demographic variables, clinical variables, all-cause
      hospitalizations, and relevant outcomes (death and renal allograft loss) for this
      patient population. The research database also allows study of major
      cardiovascular events using previously validated administrative data definitions.
      CONCLUSION: Organ failure registry linked to health administrative data can be a
      powerful tool to perform longitudinal studies in pediatric end-stage renal
      disease patients. The rich clinical and demographic information found in this
      database will facilitate study of important medical and non-medical risk factors
      for death, graft loss and cardiovascular disease among pediatric end-stage renal
      disease patients.

PMID- 20796307
TI  - Helium-oxygen reduces the production of carbon dioxide during weaning from
      mechanical ventilation.
AB  - BACKGROUND: Prolonged weaning from mechanical ventilation has a major impact on
      ICU bed occupancy and patient outcome, and has significant cost
      implications.There is evidence in patients around the period of extubation that
      helium-oxygen leads to a reduction in the work of breathing. Therefore breathing
      helium-oxygen during weaning may be a useful adjunct to facilitate weaning. We
      hypothesised that breathing helium-oxygen would reduce carbon dioxide production
      during the weaning phase of mechanical ventilation. MATERIALS/PATIENTS AND
      METHODS: We performed a prospective randomised controlled single blinded cross
      over trial on 19 adult intensive care patients without significant airways
      disease who fulfilled criteria for weaning with CPAP. Patients were randomised to
      helium-oxygen and air-oxygen delivered during a 2 hour period of CPAP
      ventilation. Carbon dioxide production (VCO2) was measured using a near patient
      main stream infrared carbon dioxide sensor and fixed orifice pneumotachograph.
      RESULTS: Compared to air-oxygen, helium-oxygen significantly decreased VCO2
      production at the end of the 2 hour period of CPAP ventilation; there was a mean
      difference in CO2 production of 48.9 ml/min (95% CI 18.7-79.2 p = 0.003) between
      the groups. There were no significant differences in other respiratory and
      haemodynamic parameters. CONCLUSION: This study shows that breathing a helium
      oxygen mixture during weaning reduces carbon dioxide production. This
      physiological study supports the need for a clinical trial of helium-oxygen
      mixture during the weaning phase of mechanical ventilation with duration of
      weaning as the primary outcome. TRIAL REGISTRATION: ISRCTN56470948.

PMID- 20796308
TI  - Tumor necrosis factor alpha sensitizes spinal cord TRPV1 receptors to the
      endogenous agonist N-oleoyldopamine.
AB  - Modulation of synaptic transmission in the spinal cord dorsal horn is thought to
      be involved in the development and maintenance of different pathological pain
      states. The proinflamatory cytokine, tumor necrosis factor alpha (TNFalpha), is
      an established pain modulator in both the peripheral and the central nervous
      system. Up-regulation of TNFalpha and its receptors (TNFR) in dorsal root
      ganglion (DRG) cells and in the spinal cord has been shown to play an important
      role in neuropathic and inflammatory pain conditions. Transient receptor
      potential vanilloid 1 (TRPV1) receptors are known as molecular integrators of
      nociceptive stimuli in the periphery, but their role on the spinal endings of
      nociceptive DRG neurons is unclear. The endogenous TRPV1 receptor agonist N
      oleoyldopamine (OLDA) was shown previously to activate spinal TRPV1 receptors. In
      our experiments the possible influence of TNFalpha on presynaptic spinal cord
      TRPV1 receptor function was investigated. Using the patch-clamp technique,
      miniature excitatory postsynaptic currents (mEPSCs) were recorded in superficial
      dorsal horn neurons in acute slices after incubation with 60 nM TNFalpha. A
      population of dorsal horn neurons with capsaicin sensitive primary afferent input
      recorded after the TNFalpha pretreatment had a basal mEPSC frequency of 1.35 +/-
      0.20 Hz (n = 13), which was significantly higher when compared to a similar
      population of neurons in control slices (0.76 +/- 0.08 Hz; n = 53; P < 0.01). In
      control slices application of a low concentration of OLDA (0.2 uM) did not evoke
      any change in mEPSC frequency. After incubation with TNFalpha, OLDA (0.2 uM)
      application to slices induced a significant increase in mEPSC frequency (155.5 +/
      17.5%; P < 0.001; n = 10). Our results indicate that TNFalpha may have a
      significant impact on nociceptive signaling at the spinal cord level that could
      be mediated by increased responsiveness of presynaptic TRPV1 receptors to
      endogenous agonists. This could be of major importance, especially during
      pathological conditions, when increased levels of TNFalpha and TNFR are present
      in the spinal cord.

PMID- 20796309
TI  - Allergic inflammation does not impact chemical-induced carcinogenesis in the
      lungs of mice.
AB  - BACKGROUND: Although the relationship between allergic inflammation and lung
      carcinogenesis is not clearly defined, several reports suggest an increased
      incidence of lung cancer in patients with asthma. We aimed at determining the
      functional impact of allergic inflammation on chemical carcinogenesis in the
      lungs of mice. METHODS: Balb/c mice received single-dose urethane (1 g/kg at day
      0) and two-stage ovalbumin during tumor initiation (sensitization: days -14 and
      0; challenge: daily at days 6-12), tumor progression (sensitization: days 70 and
      84; challenge: daily at days 90-96), or chronically (sensitization: days -14 and
      0; challenge: daily at days 6-12 and thrice weekly thereafter). In addition,
      interleukin (IL)-5 deficient and wild-type C57BL/6 mice received ten weekly
      urethane injections. All mice were sacrificed after four months. Primary end
      points were number, size, and histology of lung tumors. Secondary end-points were
      inflammatory cells and mediators in the airspace compartment. RESULTS: Ovalbumin
      provoked acute allergic inflammation and chronic remodeling of murine airways,
      evident by airspace eosinophilia, IL-5 up-regulation, and airspace enlargement.
      Urethane resulted in formation of atypical alveolar hyperplasias, adenomas, and
      adenocarcinomas in mouse lungs. Ovalbumin-induced allergic inflammation during
      tumor initiation, progression, or continuously did not impact the number, size,
      or histologic distribution of urethane-induced pulmonary neoplastic lesions. In
      addition, genetic deficiency in IL-5 had no effect on urethane-induced lung
      tumorigenesis. CONCLUSIONS: Allergic inflammation does not impact chemical
      induced carcinogenesis of the airways. These findings suggest that not all types
      of airway inflammation influence lung carcinogenesis and cast doubt on the idea
      of a mechanistic link between asthma and lung cancer.

PMID- 20796310
TI  - Thaumatin-like proteins are differentially expressed and localized in phloem
      tissues of hybrid poplar.
AB  - BACKGROUND: Two thaumatin-like proteins (TLPs) were previously identified in
      phloem exudate of hybrid poplar (Populus trichocarpa x P. deltoides) using
      proteomics methods, and their sieve element localization confirmed by
      immunofluorescence. In the current study, we analyzed different tissues to
      further understand TLP expression and localization in poplar, and used immunogold
      labelling to determine intracellular localization. RESULTS: Immunofluorescence
      using a TLP antiserum confirmed the presence of TLP in punctate, organelle-like
      structures within sieve elements. On western blots, the antiserum labeled two
      constitutively expressed proteins with distinct expression patterns. Immunogold
      labelling suggested that TLPs are associated with starch granules and starch
      containing plastids in sieve elements and phloem parenchyma cells. In addition,
      the antiserum recognized TLPs in the inner cell wall and sieve plate region of
      sieve elements. CONCLUSIONS: TLP localization in poplar cells and tissues is
      complex. TLP1 is expressed predominantly in tissues with a prominent vascular
      system such as midveins, petioles and stems, whereas the second TLP is primarily
      expressed in starch-storing plastids found in young leaves and the shoot apex.

PMID- 20796311
TI  - Lipoprotein levels and cardiovascular risk in HIV-infected and uninfected Rwandan
      women.
AB  - BACKGROUND: Lipoprotein profiles in HIV-infected African women have not been well
      described. We assessed associations of lipoprotein levels and cardiovascular risk
      with HIV-infection and CD4 count in Rwandan women. METHODS: Cross-sectional study
      of 824 (218 HIV-negative, 606 HIV+) Rwandan women. Body composition by body
      impedance analysis, CD4 count, and fasting serum total cholesterol (total-C),
      triglycerides (TG) and high-density lipoprotein (HDL) levels were measured. Low
      density lipoprotein (LDL) was calculated from Friedewald equation if TG < 400 and
      measured directly if TG >= 400 mg/dl. RESULTS: BMI was similar in HIV+ and 
      negative women, < 1% were diabetic, and HIV+ women were younger. In multivariate
      models LDL was not associated with HIV-serostatus. HDL was lower in HIV+ women
      (44 vs. 54 mg/dL, p < 0.0001) with no significant difference by CD4 count (p =
      0.13). HIV serostatus (p = 0.005) and among HIV+ women lower CD4 count (p = 0.04)
      were associated with higher TG. BMI was independently associated with higher LDL
      (p = 0.01), and higher total body fat was strongly associated with higher total-C
      and LDL. Framingham risk scores were < 2% in both groups. CONCLUSIONS: In this
      cohort of non-obese African women HDL and TG, but not LDL, were adversely
      associated with HIV infection. As HDL is a strong predictor of cardiovascular
      (CV) events in women, this HIV-associated difference may confer increased risk
      for CV disease in HIV-infected women.

PMID- 20796312
TI  - Imipenem resistance of Pseudomonas in pneumonia: a systematic literature review.
AB  - BACKGROUND: Pneumonia, and particularly nosocomial (NP) and ventilator-associated
      pneumonias (VAP), results in high morbidity and costs. NPs in particular are
      likely to be caused by Pseudomonas aeruginosa (PA), ~20% of which in
      observational studies are resistant to imipenem. We sought to identify the burden
      of PA imipenem resistance in pneumonia. METHODS: We conducted a systematic
      literature review of randomized controlled trials (RCT) of imipenem treatment for
      pneumonia published in English between 1993 and 2008. We extracted study,
      population and treatment characteristics, and proportions caused by PA. Endpoints
      of interest were: PA resistance to initial antimicrobial treatment, clinical
      success, microbiologic eradication and on-treatment emergence of resistance of
      PA. RESULTS: Of the 46 studies identified, 20 (N = 4,310) included patients with
      pneumonia (imipenem 1,667, PA 251; comparator 1,661, PA 270). Seven were double
      blind, and 7 included US data. Comparator arms included a beta-lactam (17,
      [penicillin 6, carbapenem 4, cephalosporin 7, monobactam 1]), aminoglycoside 2,
      vancomycin 1, and a fluoroquinolone 5; 5 employed double coverage. Thirteen
      focused exclusively on pneumonia and 7 included pneumonia and other diagnoses.
      Initial resistance was present in 14.6% (range 4.2-24.0%) of PA isolates in
      imipenem and 2.5% (range 0.0-7.4%) in comparator groups. Pooled clinical success
      rates for PA were 45.2% (range 0.0-72.0%) for imipenem and 74.9% (range 0.0
      100.0%) for comparator regimens. Microbiologic eradication was achieved in 47.6%
      (range 0.0%-100.0%) of isolates in the imipenem and 52.8% (range 0.0%-100.0%) in
      the comparator groups. Resistance emerged in 38.7% (range 5.6-77.8%) PA isolates
      in imipenem and 21.9% (range 4.8-56.5%) in comparator groups. CONCLUSIONS: In the
      15 years of RCTs of imipenem for pneumonia, PA imipenem resistance rates are
      high, and PA clinical success and microbiologic eradication rates are
      directionally lower for imipenem than for comparators. Conversely, initial and
      treatment-emergent resistance is more likely with the imipenem than the
      comparator regimens.

PMID- 20796313
TI  - Hunger and associated harms among injection drug users in an urban Canadian
      setting.
AB  - BACKGROUND: Food insufficiency is often associated with health risks and adverse
      outcomes among marginalized populations. However, little is known about
      correlates of food insufficiency among injection drug users (IDU). METHODS: We
      conducted a cross-sectional study to examine the prevalence and correlates of
      self-reported hunger in a large cohort of IDU in Vancouver, Canada. Food
      insufficiency was defined as reporting "I am hungry, but don't eat because I
      can't afford enough food". Logistic regression was used to determine independent
      socio-demographic and drug-use characteristics associated with food
      insufficiency. RESULTS: Among 1,053 participants, 681 (64.7%) reported being
      hungry and unable to afford enough food. Self-reported hunger was independently
      associated with: unstable housing (adjusted odds ratio [AOR]: 1.68, 95%
      confidence interval [CI]: 1.20 - 2.36, spending >= $50/day on drugs (AOR: 1.43,
      95% CI: 1.06 - 1.91), and symptoms of depression (AOR: 3.32, 95% CI: 2.45 -
      4.48). CONCLUSION: These findings suggest that IDU in this setting would likely
      benefit from interventions that work to improve access to food and social support
      services, including addiction treatment programs which may reduce the adverse
      effect of ongoing drug use on hunger.

PMID- 20796314
TI  - *omeSOM: a software for clustering and visualization of transcriptional and
      metabolite data mined from interspecific crosses of crop plants.
AB  - BACKGROUND: modern biology uses experimental systems that involve the exploration
      of phenotypic variation as a result of the recombination of several genomes. Such
      systems are useful to investigate the functional evolution of metabolic networks.
      One such approach is the analysis of transcript and metabolite profiles. These
      kinds of studies generate a large amount of data, which require dedicated
      computational tools for their analysis. RESULTS: this paper presents a novel
      software named *omeSOM (transcript/metabol-ome Self Organizing Map) that
      implements a neural model for biological data clustering and visualization. It
      allows the discovery of relationships between changes in transcripts and
      metabolites of crop plants harboring introgressed exotic alleles and furthermore,
      its use can be extended to other type of omics data. The software is focused on
      the easy identification of groups including different molecular entities,
      independently of the number of clusters formed. The *omeSOM software provides
      easy-to-visualize interfaces for the identification of coordinated variations in
      the co-expressed genes and co-accumulated metabolites. Additionally, this
      information is linked to the most widely used gene annotation and metabolic
      pathway databases. CONCLUSIONS: *omeSOM is a software designed to give support to
      the data mining task of metabolic and transcriptional datasets derived from
      different databases. It provides a user-friendly interface and offers several
      visualization features, easy to understand by non-expert users. Therefore,
      *omeSOM provides support for data mining tasks and it is applicable to basic
      research as well as applied breeding programs. The software and a sample dataset
      are available free of charge at http://sourcesinc.sourceforge.net/omesom/.

PMID- 20796315
TI  - Proprietary arabinogalactan extract increases antibody response to the pneumonia
      vaccine: a randomized, double-blind, placebo-controlled, pilot study in healthy
      volunteers.
AB  - BACKGROUND: Arabinogalactan from Larch tree (Larix spp.) bark has previously
      demonstrated immunostimulatory activity. The purpose of this study was to test
      the hypothesis that ingestion of a proprietary arabinogalactan extract,
      ResistAidTM, would selectively enhance the antibody response to the pneumococcal
      (pneumonia) vaccine in healthy adults. METHODS: This randomized, double-blind,
      placebo-controlled, parallel group pilot study included 45 healthy adults who had
      not previously been vaccinated against Streptococcus pneumoniae. The volunteers
      began taking the study product or placebo (daily dosage 4.5 g) at the screening
      visit (V1-Day 0) and continued over the entire 72 day study period. After 30 days
      the subjects received the 23-valent pneumococcal vaccine (V2). They were
      monitored the following day (V3-Day 31), as well as 21 days (V4-Day 51) and 42
      days (V5-Day 72) after vaccination. Responses by the adaptive immune system
      (antigen specific) were measured via pneumococcal IgG antibodies (subtypes 4, 6B,
      9V, 14, 18C, 19F, and 23F) and salivary IgA levels. Responses by the innate
      immune system (non-specific) were measured via white blood cell counts,
      inflammatory cytokines and the complement system. RESULTS: Vaccination
      significantly increased pneumococcal IgG levels as expected. The arabinogalactan
      group demonstrated a statistically significant greater IgG antibody response than
      the placebo group in two antibodies subtypes (18C and 23F) at both Day 51 (p =
      0.006 and p = 0.002) and at Day 72 (p = 0.008 and p = 0.041). These same subtypes
      (18C and 23F) also demonstrated change scores from baseline which were
      significant, in favor of the arabinogalactan group, at Day 51 (p = 0.033 and
      0.001) and at Day 72 (p = 0.012 and p = 0.003). Change scores from baseline and
      mean values were greater in the arabinogalactan group than placebo for most time
      points in antibody subtypes 4, 6B, 9V, and 19F, but these differences did not
      reach statistical significance. There was no effect from the vaccine or
      arabinogalactan on salivary IgA, white blood cell count, inflammatory cytokines
      or complement. CONCLUSIONS: The proprietary arabinogalactan extract (ResistAid),
      tested in this randomized, double-blind, placebo-controlled, parallel-group pilot
      study, increased the antibody response of healthy volunteers to the 23-valent
      pneumococcal vaccine compared to placebo. TRIAL REGISTRATION: ISRCTN98817459.

PMID- 20796316
TI  - Elevated c-Src and c-Yes expression in malignant skin cancers.
AB  - BACKGROUND: Src family kinases (SFKs) play an important role in cancer
      proliferation, survival, motility, invasiveness, metastasis, and angiogenesis.
      Among the SFKs, c-Src and c-Yes are particularly over-expressed or hyper
      activated in many human epithelial cancers. However, only a few studies have
      attempted to define the expression and role of c-Src and c-Yes in cutaneous
      carcinomas. OBJECTIVES: To investigate the expression of c-Src and c-Yes in
      cutaneous carcinomas to include malignant melanoma (MM), squamous cell carcinoma
      (SCC) and basal cell carcinoma (BCC). METHODS: We examined 6 normal skin tissues
      and 18 malignant skin tumor tissues using western blotting for the expression of
      c-Src and c-Yes. In another set, 16 specimens of MM, 16 SCCs and 16 BCCs were
      analyzed for the expression of c-Src and c-Yes using immunohistochemical
      staining. RESULTS: Western blotting showed that c-Src was expressed in all
      malignant skin tumors, but not in normal skin, while c-Yes was expressed in MM
      and SCC, but not in BCC and normal skin. Immunohistochemical staining results of
      c-Src and c-Yes in MM, SCC, and BCC mirrored those of the western blot analysis.
      CONCLUSIONS: c-Src, rather than c-Yes, plays a key role in the proliferation and
      progression of malignant skin cancers.

PMID- 20796317
TI  - E-selectin gene polymorphisms are associated with essential hypertension: a case
      control pilot study in a Chinese population.
AB  - BACKGROUND: Genetic variation is thought to contribute to the etiology of
      hypertension, and E-selectin is a candidate essential hypertension-associated
      gene. This study thus sought to investigate possible genetic associations between
      the T1880C, C602A and T1559C polymorphisms of E-selectin and essential
      hypertension. METHODS: Hypertensive patients (n = 490) and healthy normotensive
      subjects (n = 495) were screened for the genotypes T1880C, C602A and T1559C using
      real-time quantitative polymerase chain reaction after DNA extraction to identify
      representative variations in the E-selectin gene. The associations between
      genotypes and alleles of the three mutations and essential hypertension were then
      analyzed using a case-control study. RESULTS: Hypertensive patients and
      normotensive subjects were significantly different with respect to the genotypes
      CC, CA and AA (P = 0.005) and the C-allele frequency of C602A (P = 0.001). A
      comparison of dominant versus recessive models also revealed significant
      differences between the two groups (P = 0.004 and P = 0.02). When subgrouped by
      gender, these indexes differed significantly between normotensive and essential
      hypertensive males, but not in females. The additive model of the T1559C genotype
      did not differ between essential hypertensive and normotensive groups overall (P
      = 0.39), but it was different between hypertensive and normotensive males (P =
      0.046) and females (P = 0.045). The CC + TC versus TT frequency of T1559C was
      also different in the recessive model of male hypertensive and normotensive
      groups (P = 0.02). Further analysis showed that C602A and T1559C were
      significantly associated with hypertension (C602A: OR = 7.58, 95%CI = 1.53-11.97,
      P < 0.01; and T1559C: OR = 6.77, 95%CI = 1.07-1.83, P < 0.05). The frequency of
      the C-C-C haplotype was significantly higher in hypertensive patients than in
      control individuals as well as in hypertensive and normotensive males (P = 0.008
      and 0.01). The frequency of the C-A-T haplotype was higher only in male
      hypertensives and normotensives (P = 0.015). Furthermore, there was a significant
      interaction between E-selectin and gender (P = 0.02 for C602A and 0.04 for
      T1559C). CONCLUSION: C602A and T1559C may be independent risk factors for
      essential hypertension in the Chinese population, whereas T1880C is not.

PMID- 20796319
TI  - Activation of voltage-gated KCNQ/Kv7 channels by anticonvulsant retigabine
      attenuates mechanical allodynia of inflammatory temporomandibular joint in rats.
AB  - BACKGROUND: Temporomandibular disorders (TMDs) are characterized by persistent
      orofacial pain and have diverse etiologic factors that are not well understood.
      It is thought that central sensitization leads to neuronal hyperexcitability and
      contributes to hyperalgesia and spontaneous pain. Nonsteroidal anti-inflammatory
      drugs (NSAIDs) are currently the first choice of drug to relieve TMD pain. NSAIDS
      were shown to exhibit anticonvulsant properties and suppress cortical neuron
      activities by enhancing neuronal voltage-gated potassium KCNQ/Kv7 channels (M
      current), suggesting that specific activation of M-current might be beneficial
      for TMD pain. RESULTS: In this study, we selected a new anticonvulsant drug
      retigabine that specifically activates M-current, and investigated the effect of
      retigabine on inflammation of the temporomandibular joint (TMJ) induced by
      complete Freund's adjuvant (CFA) in rats. The results show that the head
      withdrawal threshold for escape from mechanical stimulation applied to facial
      skin over the TMJ in inflamed rats was significantly lower than that in control
      rats. Administration of centrally acting M-channel opener retigabine (2.5 and 7.5
      mg/kg) can dose-dependently raise the head withdrawal threshold of mechanical
      allodynia, and this analgesic effect can be reversed by the specific KCNQ channel
      blocker XE991 (3 mg/kg). Food intake is known to be negatively associated with
      TMJ inflammation. Food intake was increased significantly by the administration
      of retigabine (2.5 and 7.5 mg/kg), and this effect was reversed by XE991 (3
      mg/kg). Furthermore, intracerebralventricular injection of retigabine further
      confirmed the analgesic effect of central retigabine on inflammatory TMJ.
      CONCLUSIONS: Our findings indicate that central sensitization is involved in
      inflammatory TMJ pain and pharmacological intervention for controlling central
      hyperexcitability by activation of neuronal KCNQ/M-channels may have therapeutic
      potential for TMDs.

PMID- 20796318
TI  - Gap junctions in olfactory neurons modulate olfactory sensitivity.
AB  - BACKGROUND: One of the fundamental questions in olfaction is whether olfactory
      receptor neurons (ORNs) behave as independent entities within the olfactory
      epithelium. On the basis that mature ORNs express multiple connexins, I
      postulated that gap junctional communication modulates olfactory responses in the
      periphery and that disruption of gap junctions in ORNs reduces olfactory
      sensitivity. The data collected from characterizing connexin 43 (Cx43) dominant
      negative transgenic mice OlfDNCX, and from calcium imaging of wild type mice (WT)
      support my hypothesis. RESULTS: I generated OlfDNCX mice that express a dominant
      negative Cx43 protein, Cx43/beta-gal, in mature ORNs to inactivate gap junctions
      and hemichannels composed of Cx43 or other structurally related connexins.
      Characterization of OlfDNCX revealed that Cx43/beta-gal was exclusively expressed
      in areas where mature ORNs resided. Real time quantitative PCR indicated that
      cellular machineries of OlfDNCX were normal in comparison to WT.
      Electroolfactogram recordings showed decreased olfactory responses to
      octaldehyde, heptaldehyde and acetyl acetate in OlfDNCX compared to WT.
      Octaldehyde-elicited glomerular activity in the olfactory bulb, measured
      according to odor-elicited c-fos mRNA upregulation in juxtaglomerular cells, was
      confined to smaller areas of the glomerular layer in OlfDNCX compared to WT. In
      WT mice, octaldehyde sensitive neurons exhibited reduced response magnitudes
      after application of gap junction uncoupling reagents and the effects were
      specific to subsets of neurons. CONCLUSIONS: My study has demonstrated that
      altered assembly of Cx43 or structurally related connexins in ORNs modulates
      olfactory responses and changes olfactory activation maps in the olfactory bulb.
      Furthermore, pharmacologically uncoupling of gap junctions reduces olfactory
      activity in subsets of ORNs. These data suggest that gap junctional communication
      or hemichannel activity plays a critical role in maintaining olfactory
      sensitivity and odor perception.

PMID- 20796320
TI  - CMASA: an accurate algorithm for detecting local protein structural similarity
      and its application to enzyme catalytic site annotation.
AB  - BACKGROUND: The rapid development of structural genomics has resulted in many
      "unknown function" proteins being deposited in Protein Data Bank (PDB), thus, the
      functional prediction of these proteins has become a challenge for structural
      bioinformatics. Several sequence-based and structure-based methods have been
      developed to predict protein function, but these methods need to be improved
      further, such as, enhancing the accuracy, sensitivity, and the computational
      speed. Here, an accurate algorithm, the CMASA (Contact MAtrix based local
      Structural Alignment algorithm), has been developed to predict unknown functions
      of proteins based on the local protein structural similarity. This algorithm has
      been evaluated by building a test set including 164 enzyme families, and also
      been compared to other methods. RESULTS: The evaluation of CMASA shows that the
      CMASA is highly accurate (0.96), sensitive (0.86), and fast enough to be used in
      the large-scale functional annotation. Comparing to both sequence-based and
      global structure-based methods, not only the CMASA can find remote homologous
      proteins, but also can find the active site convergence. Comparing to other local
      structure comparison-based methods, the CMASA can obtain the better performance
      than both FFF (a method using geometry to predict protein function) and SPASM (a
      local structure alignment method); and the CMASA is more sensitive than PINTS and
      is more accurate than JESS (both are local structure alignment methods). The
      CMASA was applied to annotate the enzyme catalytic sites of the non-redundant
      PDB, and at least 166 putative catalytic sites have been suggested, these sites
      can not be observed by the Catalytic Site Atlas (CSA). CONCLUSIONS: The CMASA is
      an accurate algorithm for detecting local protein structural similarity, and it
      holds several advantages in predicting enzyme active sites. The CMASA can be used
      in large-scale enzyme active site annotation. The CMASA can be available by the
      mail-based server (http://159.226.149.45/other1/CMASA/CMASA.htm).

PMID- 20796321
TI  - Intron-loss evolution of hatching enzyme genes in Teleostei.
AB  - BACKGROUND: Hatching enzyme, belonging to the astacin metallo-protease family,
      digests egg envelope at embryo hatching. Orthologous genes of the enzyme are
      found in all vertebrate genomes. Recently, we found that exon-intron structures
      of the genes were conserved among tetrapods, while the genes of teleosts
      frequently lost their introns. Occurrence of such intron losses in teleostean
      hatching enzyme genes is an uncommon evolutionary event, as most eukaryotic genes
      are generally known to be interrupted by introns and the intron insertion sites
      are conserved from species to species. Here, we report on extensive studies of
      the exon-intron structures of teleostean hatching enzyme genes for insight into
      how and why introns were lost during evolution. RESULTS: We investigated the
      evolutionary pathway of intron-losses in hatching enzyme genes of 27 species of
      Teleostei. Hatching enzyme genes of basal teleosts are of only one type, which
      conserves the 9-exon-8-intron structure of an assumed ancestor. On the other
      hand, otocephalans and euteleosts possess two types of hatching enzyme genes,
      suggesting a gene duplication event in the common ancestor of otocephalans and
      euteleosts. The duplicated genes were classified into two clades, clades I and
      II, based on phylogenetic analysis. In otocephalans and euteleosts, clade I genes
      developed a phylogeny-specific structure, such as an 8-exon-7-intron, 5-exon-4
      intron, 4-exon-3-intron or intron-less structure. In contrast to the clade I
      genes, the structures of clade II genes were relatively stable in their
      configuration, and were similar to that of the ancestral genes. Expression
      analyses revealed that hatching enzyme genes were high-expression genes, when
      compared to that of housekeeping genes. When expression levels were compared
      between clade I and II genes, clade I genes tends to be expressed more highly
      than clade II genes. CONCLUSIONS: Hatching enzyme genes evolved to lose their
      introns, and the intron-loss events occurred at the specific points of teleostean
      phylogeny. We propose that the high-expression hatching enzyme genes frequently
      lost their introns during the evolution of teleosts, while the low-expression
      genes maintained the exon-intron structure of the ancestral gene.

PMID- 20796322
TI  - Spatial patterns of diabetes related health problems for vulnerable populations
      in Los Angeles.
AB  - BACKGROUND: Rates for Diabetes Mellitus continue to rise in most urban areas of
      the United States, with a disproportionate burden suffered by minorities and low
      income populations. This paper presents an approach that utilizes address level
      data to understand the geography of this disease by analyzing patients seeking
      diabetes care through an emergency department in a Los Angeles County hospital.
      The most vulnerable frequently use an emergency room as a common care access
      point, and such care is especially costly. A fine scale GIS analysis reveals
      hotspots of diabetes related health problems and provides output useful in a
      clinic setting. Indeed these results were used to support the work of a
      progressive diabetes clinic to guide management and intervention strategies.
      RESULTS: Hotspots of diabetes related health problems, including neurological and
      kidney issues were mapped for vulnerable populations in a central section of Los
      Angeles County. The resulting spatial grid of rates and significance were
      overlaid with new patient residential addresses attending an area clinic. In this
      way neighbourhood diabetes health characteristics are added to each patient's
      individual health record. Of the 29 patients, 4 were within statistically
      significant hotspots for at least one of the conditions being investigated.
      CONCLUSIONS: Although exploratory in nature, this approach demonstrates a novel
      method to conduct GIS based investigations of urban diabetes while providing
      support to a progressive diabetes clinic looking for novel means of managing and
      intervention. In so doing, this analysis adds to a relatively small literature on
      fine scale GIS facilitated diabetes research. Similar data should be available
      for most hospitals, and with due consideration for preserving spatial
      confidentiality, analysis outputs such as those presented here should become more
      commonly employed in other investigations of chronic diseases.

PMID- 20796323
TI  - Transcription, one allele at a time.
AB  - A recent study presents a technique allowing one to image transcription from a
      single gene copy in live cells, and highlights the dynamic nature of
      transcriptional regulation.

PMID- 20796324
TI  - The past is a foreign country.

PMID- 20796325
TI  - A new interpretation of components in the ERG signals to sine wave luminance
      stimuli at different temporal frequencies and contrasts.
AB  - Full-field electroretinograms were recorded from five normal human subjects using
      white light (mean luminance: 250 cd/m2) sine wave stimuli at different
      frequencies and contrasts. In agreement with previous studies, we found that the
      amplitude of the fundamental component displayed a dip at about 12 Hz, coinciding
      with a maximum in the second harmonic component, indicating frequency doubling of
      the responses. By including measurements at different contrasts, we were able to
      recognize two (sine-like and transient) response components. We found that the
      waveform of the transient response was relatively frequency independent. An
      algorithm to separate the two components was developed. The interaction between
      these two components can explain the frequency-doubled responses around 12 Hz.
      The sine-like component is more linear and prominent in the low-frequency region,
      whereas the transient seems to be more nonlinear and prominent in the high
      frequency region.

PMID- 20797310
TI  - Nutrition economics - characterising the economic and health impact of nutrition.
AB  - There is a new merging of health economics and nutrition disciplines to assess
      the impact of diet on health and disease prevention and to characterise the
      health and economic aspects of specific changes in nutritional behaviour and
      nutrition recommendations. A rationale exists for developing the field of
      nutrition economics which could offer a better understanding of both nutrition,
      in the context of having a significant influence on health outcomes, and
      economics, in order to estimate the absolute and relative monetary impact of
      health measures. For this purpose, an expert meeting assessed questions aimed at
      clarifying the scope and identifying the key issues that should be taken into
      consideration in developing nutrition economics as a discipline that could
      potentially address important questions. We propose a first multidisciplinary
      outline for understanding the principles and particular characteristics of this
      emerging field. We summarise here the concepts and the observations of workshop
      participants and propose a basic setting for nutrition economics and health
      outcomes research as a novel discipline to support nutrition, health economics
      and health policy development in an evidence and health-benefit-based manner.

PMID- 20797311
TI  - A new aphid genus Neoaulacorthum (Hemiptera: Aphididae: Macrosiphini), determined
      by molecular and morphometric analyses.
AB  - We performed molecular and morphological analyses to determine the generic limit
      of the genus Aulacorthum, including several species with controversial taxonomic
      histories. The sequences of four mitochondrial genes, COI, COII, srRNA and lrRNA,
      and one nuclear gene, EF1a, implied that Aulacorthum is not monophyletic, with
      Aulacorthum magnoliae and Aulacorthum nipponicum forming a clade that is not
      sister to other currently recognized Aulacorthum species. Morphometric analysis
      based on 20 morphological characters also showed that A. magnoliae and A.
      nipponicum exhibited morphological characteristics distinct from congeneric
      species. Based on these results, we propose a new genus, Neoaulacorthum ge. n.,
      for A. magnoliae and A. nipponicum.

PMID- 20797312
TI  - GP130 cytokines and bone remodelling in health and disease.
AB  - Cytokines that bind to and signal through the gp130 co-receptor subunit include
      interleukin (IL)-6, IL-11, oncostatin M (OSM), leukemia inhibitory factor (LIF),
      cardiotrophin-1 (CT-1), and ciliary neutrophic factor (CNTF). Apart from
      contributing to inflammation, gp130 signalling cytokines also function in the
      maintenance of bone homeostasis. Expression of each of these cytokines and their
      ligand-specific receptors is observed in bone and joint cells, and bone-active
      hormones and inflammatory cytokines regulate their expression. gp130 signalling
      cytokines have been shown to regulate the differentiation and activity of
      osteoblasts, osteoclasts and chondrocytes. Furthermore, cytokine and receptor
      specific gene-knockout mouse models have identified distinct roles for each of
      these cytokines in regulating bone resorption, bone formation and bone growth.
      This review will discuss the current models of paracrine and endocrine actions of
      gp130-signalling cytokines in bone remodelling and growth, as well as their
      impact in pathologic bone remodelling evident in periodontal disease, rheumatoid
      arthritis, spondylarthropathies and osteoarthritis.

PMID- 20797313
TI  - New understanding of glucocorticoid action in bone cells.
AB  - Glucocorticoids (GCs) are useful drugs for the treatment of various diseases, but
      their use for prolonged periods can cause severe side effects such as
      osteoporosis. GCs have a direct effect on bone cells, where they can arrest bone
      formation, in part through the inhibition of osteoblast. On the other hand, GCs
      potently suppress osteoclast resorptive activity by disrupting its cytoskeleton
      based on the inhibition of RhoA, Rac and Vav3 in response to macrophage colony
      stimulating factor. GCs also interfere with microtubule distribution and
      stability, which are critical for cytoskeletal organization in osteoclasts. Thus,
      GCs inhibit microtubule-dependent cytoskeletal organization in osteoclasts,
      which, in the context of bone remodeling, further dampens bone formation.

PMID- 20797314
TI  - The effect of CYP1A2 gene polymorphisms on Theophylline metabolism and chronic
      obstructive pulmonary disease in Turkish patients.
AB  - Cytochrome P450 (CYP) 1A2 gene polymorphisms are thought to be involved in the
      metabolism of theophylline (TP). We aimed to investigate the effect of CYP1A2*1C,
      CYP1A2*1D, CYP1A2*1E, and CYP1A2*1F polymorphisms of the CYP1A2 on TP metabolism
      by PCR-RFLP in 100 Turkish patients with chronic obstructive pulmonary disease
      (COPD) receiving TP. One hundred and one healthy volunteers were included as
      control group. The genotype frequencies of the CYP1A2*1D and CYP1A2*1F were found
      to be significantly different in the patients compared to the controls. The "T"
      allele at -2467 delT and the "C" allele at -163 C > A in the CYP1A2 displayed
      association with a significantly increased risk for COPD. "T" allele at - 2467
      delT was also associated with a high risk of disease severity in COPD. In
      conclusion, our data suggest that genetic alterations in CYP1A2 may play a role
      both in the pharmacogenetics of TP and in the development of COPD.

PMID- 20797315
TI  - Severely modified lipoprotein properties without a change in cholesteryl ester
      transfer protein activity in patients with acute renal failure secondary to
      Hantaan virus infection.
AB  - Patients with hemorrhagic fever with renal syndrome (HFRS) often exhibit altered
      serum lipid and lipoprotein profile during the oliguric phase of the disease.
      Serum lipid and lipoprotein profiles were assessed during the oliguric and
      recovery phases in six male patients with HFRS. In the oliguric phase of HFRS,
      the apolipoprotein (apo) C-III content in high-density lipoproteins (HDL) was
      elevated, whereas the apoA-I content was lowered. The level of expression and
      activity of antioxidant enzymes were severely reduced during the oliguric phase,
      while the cholesteryl ester transfer protein activity and protein level were
      unchanged between the phases. In the oliguric phase, electromobility of HDL2 and
      HDL3 was faster than in the recovery phase. Low-density lipoprotein (LDL)
      particle size was smaller and the distribution was less homogeneous. Patients
      with HFRS in the oliguric phase had severely modified lipoproteins in composition
      and metabolism.

PMID- 20797316
TI  - Large scale purification and characterization of recombinant human
      autotaxin/lysophospholipase D from mammalian cells.
AB  - We utilized a mammalian expression system to purify and characterize autotaxin
      (ATX)/lysophospholipase D, an enzyme present in the blood responsible for
      biosynthesis of lysophosphatidic acid. The human ATX cDNA encoding amino acids 29
      915 was cloned downstream of a secretion signal of CD5. At the carboxyl terminus
      was a thrombin cleavage site followed by the constant domain (Fc) of IgG to
      facilitate protein purification. The ATX-Fc fusion protein was expressed in
      HEK293 cells and isolated from conditioned medium of a stable clone by affinity
      chromatography with Protein A sepharose followed by cleavage with thrombin. The
      untagged ATX protein was further purified to essential homogeneity by gel
      filtration chromatography with a yield of approximately 5 mg/liter medium. The
      purified ATX protein was enzymatically active and biologically functional,
      offering a useful tool for further biological and structural studies of this
      important enzyme.

PMID- 20797317
TI  - Analysis of copy number variation in 8,842 Korean individuals reveals 39 genes
      associated with hepatic biomarkers AST and ALT.
AB  - Biochemical tests such as aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT) are useful for diagnosing patients with liver disease. In
      this study, we tested the association between copy number variation and the
      hepatic biomarkers AST and ALT based on 8,842 samples from population-based
      cohorts in Korea. We used Affymetrix Genome-Wide Human 5.0 arrays and identified
      10,534 CNVs using HelixTree software. Of the CNVs tested using univariate linear
      regression, 100 CNVs were significant for AST and 16 were significant for ALT (P
      < 0.05). We identified 39 genes located within the CNV regions. DKK1 and HS3ST3B1
      were shown to play roles in heparan sulfate biosynthesis and the Wnt signaling
      pathway, respectively. NAF1 and NPY1R were associated with glycoprotein processes
      and neuropeptide Y receptor activity based on GO categories. PTER, SOX14 and
      TM7SF4 were expressed in liver. DPYS and CTSC were found to be associated with
      dihydropyrimidinuria and Papillon-Lefevre syndrome phenotypes using OMIM. NPY5R
      was found to be associated with dyslipidemia using the Genetic Association
      Database.

PMID- 20797319
TI  - Enhancement of HIV-1 Tat fusion protein transduction efficiency by bog blueberry
      anthocyanins.
AB  - Though protein transduction domains (PTDs) are well known for the delivery of
      exogenous therapeutic proteins into living cells, the overall low efficiency of
      transduction is a serious obstacle. We investigated the effect of bog blueberry
      anthocyanins (BBA) on protein transduction efficiency and found that BBA enhanced
      the transduction efficiencies of Tat-SOD fusion protein into HeLa cells and mice
      skin. The enzymatic activities in the cells and skin tissue in the presence of
      BBA were markedly increased compared to controls. Further, BBA did not
      demonstrate any cell toxicity at various concentrations. Although the mechanism
      is not fully understood, we suggest that BBA might alter the conformation of the
      membrane, which would indicate that BBA can be used as a protein transduction
      enhancer for the efficient delivery of therapeutic proteins for a variety of
      disorders.

PMID- 20797318
TI  - Smad4 mediates malignant behaviors of human ovarian carcinoma cell through the
      effect on expressions of E-cadherin, plasminogen activator inhibitor-1 and VEGF.
AB  - Smad4 is involved in cancer progression and metastasis. Using a pair of human
      syngeneic epithelial ovarian cancer cells with low (HO-8910) and high (HO-8910PM)
      metastatic abilities, we aimed to reveal the role of Smad4 in ovarian cancer
      metastasis in vitro. Smad4 was down-regulated in HO-8910PM cell line relative to
      HO-8910 by implicating Smad4 was probably a potential tumor suppressor gene for
      ovarian cancer. Re-expression of Smad4 decreased the migration ability and
      inhibited the invasion capacity of HO-8910PM, while promoted the cell adhesion
      capacity for HO-8910PM. The stable expression of Smad4 increased the expression
      of E-cadherin, reduced the expression of plasminogen activator inhibitor-1 (PAI
      1) and slightly down-regulated the expression of VEGF. Smad4 suppresses human
      ovarian cancer cell metastasis potential through its effect on the expressions of
      PAI-1, E-cadherin and VEGF. Results from current work implicate Smad4 might
      suppress the invasion and metastasis of human ovarian tumor cells through a TGF
      Beta/Smad-mediated pathway.

PMID- 20797320
TI  - Optimizing the binding activity of the AP2/ERF transcription factor with the GCC
      box element from Brassica napus by directed evolution.
AB  - In this study, we cloned the ERF-B3 subfamily transcription factor gene BnaERF-B3
      hy15 from Brassica napus L. Huyou15. This 600 bp gene encodes a 199 amino acid
      classic ethylene responsive factor (ERF), which shown no binding or very weak
      binding GCC box-binding activity by the yeast one-hybrid assay. We used gene
      shuffling and the yeast one-hybrid system to obtain three mutated sequences that
      can bind to the GCC box. Sequence analysis indicated that two residues, Gly156 in
      the AP2 domain and Phe62 at the N-terminal domain were mutated to arginine and
      serine, respectively. Changes of Gly156 to arginine and Phe62 to serine increased
      the GCCbinding activity of BnaERF-B3-hy15 and the alter of Gly156 to arginine
      changed the AP2-domain structure of BnaERF-B3- hy15.

PMID- 20797321
TI  - Molecular characterization and inhibition analysis of the acetylcholinesterase
      gene from the silkworm maggot, Exorista sorbillans.
AB  - Several organophosphorus (OP) insecticides can selectively kill the silkworm
      maggot, Exorista sorbillans (Es) (Diptera: Tachinidae), while not obviously
      affecting the host (Bombyx mori) larvae, but the mechanism is not yet clear. In
      this study, the cDNA encoding an acetylcholinesterase (AChE) from the field Es
      was isolated. One point mutation (Gly353Ala) was identified. The Es-353G AChE and
      Es-353A AChE were expressed in baculovirus- insect cell system, respectively. The
      inhibition results showed that for eserine and Chlorpyrifos, Es-353A AChE was
      significantly less sensitive than Es-353G AChE. Meanwhile, comparison of the
      I(50) values of eserine, dichlorvos, Chlorpyrifos and omethoate of recombinant Es
      AChEs with its host (Bombyx mori) AChEs indicated that, both Es AChEs are more
      sensitive than B. mori AChEs. The results give an insight of the mechanism that
      some OP insecticides can selectively kills Es while without distinct effect on
      its host, B. mori.

PMID- 20797322
TI  - Effects of network development on attitudes towards work and well-being at work
      among health care staff in northern Finland.
AB  - OBJECTIVES: To assess the effects of network development between primary and
      special health care units on attitudes towards work and well-being at work among
      health care staff. STUDY DESIGN: A prospective quasi-experimental design with
      intervention (n=33) and control (n=23) groups. This 2-year pilot intervention
      study was implemented in 14 health centres and 4 hospitals in northern Finland.
      METHODS: The material was gathered via self-reported questionnaires from the
      health care staff at baseline and 1 follow-up. The intervention was composed of
      regional networking, self-ruling teamwork, staff education and guidance for the
      multiprofessional teams consisting of participants from primary and special
      health care units. The objective of these teams was to construct and disseminate
      regional models of patient education for the service process of 6 patient groups:
      cardiovascular, COPD, total joint replacement, cerebral infarction, cancer and
      chronic ulcer patients. RESULTS: The network development intervention had
      positive effects on attitudes towards work concerning organizational commitment,
      occupational commitment and growth satisfaction. The positive effects were also
      found in well-being at work, measured by absorption. The results are encouraging,
      although the study failed to demonstrate statistically significant improvements
      in other attitude and well-being outcomes that were measured. CONCLUSIONS:
      Network development intervention particularly improved positive attitudes towards
      work among health care staff. Although randomized controlled trials are needed,
      regional network development between health centres and hospitals is recommended
      when the goal is positive attitudes towards work and well-being at work in
      sparsely populated and rural areas.

PMID- 20797324
TI  - [A preliminary study on the origin of human lung adenocarcinoma stem cells from
      lung bonchioalveolar stem cells.].
AB  - BACKGROUND: Lung adenocarcinomas are proposed to originate from the malignant
      transformation of bronchioalveolar stem cells (BASC). This hypothesis, however,
      has not been confirmed in humans yet. In the present study, we determined to
      analyze the BASC properties in human lung adenocarcinoma stem cells. METHODS: The
      human lung adenocarcinoma stem cells were obtained by flow cytometry (FCM) and
      induced with the sphereforming assay. The markers associated with BASC were
      measured by immunofluorescent staining, and their metastatic capacity was
      evaluated by injecting into NOD/SCID mice via tail vein. RESULTS: The majority of
      A549 and SPC-A1 human lung adenocarcinoma cells expressed the type II alveolar
      cell-specific marker SP-C. However, a minority of cells also expressed the
      bronchiolar Clara cell-specific marker CCSP and the embryonic stem cell marker
      OCT4, suggesting that these cells may belong to cancer stem cells with BASC
      properties. The CD24(+)CD221(+) human lung adenocarcinoma stem cells were
      purified by FCM and then subjected to the immunofluorescent staining. The results
      documented that these cells had the phenotype of CCSP(+)SP-C(+)OCT4(+), with the
      same phenotype as mouse BASC. Furthermore, the floatgrowing spheres (named
      pulmospheres) were developed after 2-week incubation of cancer cells in the serum
      free medium containing EGF, IGF-1, and FGF-10. Again, the resultant pulmosphere
      cells had the phenotype of BASC. These cells were able to differentiate when
      incubated for two weeks in serum-containing conditions, exhibiting the loss of
      CCSP and OCT4 markers. Animal studies indicated that the pulmosphere cells had
      the highly metastatic capacity. CONCLUSIONS: The human lung adenocarcinoma stem
      cells may originate from the transformation of BASC, as their mouse counterparts.
      These primitive cancer cells are characterized to express the BASC markers as
      well as the embryonic stem cell gene OCT4.

PMID- 20797323
TI  - Hypertension among the Inuit from Nunavik: should we expect an increase because
      of obesity?
AB  - OBJECTIVES: Because of their recent adoption of a Westernized lifestyle, an
      increased risk of developing hypertension (HTN) is suspected among Inuit
      populations. This study aimed to assess the exact prevalence of HTN in Nunavik
      Inuit and to examine its association with other major risk factors of
      cardiovascular disease. STUDY DESIGN: A cross-sectional population-based study.
      METHODS: We analysed biological and anthropometric data and the medical history
      of 832 Inuit. RESULTS: The overall prevalence of HTN (>=140/90 mmHg or the use of
      medication) was 19% with no gender difference. Obesity (body mass index [BMI]
      >=30 kg/m(2)) was the highest prevalent cardiovascular risk factor (23%), and was
      significantly associated with HTN (OR for BMI<25 kg/m(2) vs. BMI 30-34 kg/m(2):
      7.9 [3.5-17.9]; OR for BMI<25 kg/m(2) vs. BMI >=35 kg/m(2): 14.4 [5.6-36.7]). An
      increase in odds of prehypertension (preHTN) (130-139/80-89 mmHg) was also
      observed as the BMI increased (p for trend, p<0.0001). CONCLUSION: The prevalence
      of HTN in the Inuit populations has reached values similar to those of their
      Westernized counterparts. Furthermore, not only HTN but also preHTN states are
      significantly associated with obesity even after adjusting for confounding
      variables. These results clearly indicate that HTN is becoming a growing health
      challenge in Nunavik because of pandemic obesity.

PMID- 20797325
TI  - [Experimental study of targeting MMP-9 deoxyribozyme role of adhesion and
      migration in human lung adenocarcinoma cancer cell.].
AB  - BACKGROUND: Deoxyribozyme has high biocatalytic activity and sequence specificity
      against the target mRNA and inhibits gene expression at mRNA level. The aim of
      this study is to investigate the impact of targeting MMP-9 deoxyribozyme to cell
      adhesion and migration in human lung adenocarcinoma cell line A549. METHODS: The
      targeting MMP-9 deoxyribozyme was designed by oligofectamine into human lung
      adenocarcinoma cell line A549. The expression of MMP-9 in cell was detected by
      Western blot. The cell adhesion and migration after the intervention of
      deoxyribozyme was observed. RESULTS: After targeting MMP-9 deoxyribozyme
      intervention, the expression of MMP-9 in the cells compared with the control
      group was significantly lower (P <0.01), at the same time, the rate of cell
      adhesion and migration were significantly decreased. CONCLUSIONS: Targeting MMP-9
      deoxyribozyme inhibited the expression of MMP-9 in human lung adenocarcinoma cell
      line A549 and effectively prevent cell adhesion and migration.

PMID- 20797326
TI  - [The prognostic value of detection of serum VEGF-C level and lymphangiogenesis in
      mediastinal lymph nodes in the patients with lung cancer.].
AB  - BACKGROUND: There is still lack of special prognostic factor on lung cancer, this
      study will explore the prognostic value of serum VEGF-C level and
      lymphangiogenesis of primary cancer and mediastinal lymph nodes in the patients
      with lung cancer. METHODS: Thirty patients with NSCLC would accept operation (new
      group) and 30 cases followed up three years postoperative (history group) were
      chosen respectively. The serum VEGF-C level of new group was tested. The VEGF-C
      and LYVE-1 expression in the mediastinal lymph nodes were put in practice between
      two groups. The relationship was analyzed for the serum VEGF-C level, VEGF-C and
      LYVE-1 expression of primary cancer and mediastinal lymph nodes, mediastinal
      lymph nodes metastasis and the 3-year survival rate of the patients. RESULTS:
      (1)In new group, the serum VEGF-C level of N2 patients was significantly higher
      than that of non-N2 patients. (2)In new group, the serum VEGF-C level was closely
      correlated with VEGF-C expression of primary cancer. (3)In two groups, the
      primary cancer and mediastinal metastasis lymph nodes had high VEGF-C expression.
      (4)VEGF-C expression of primary cancer and mediastinal lymph nodes was closely
      correlated with LYVE-1 expression between the two groups. (5)VEGF-C and LYVE-1
      expression of N2 patients was significantly higher than that of non-N2 patients
      between two groups. (6)The patients' 3-year-survival rate was closely correlated
      with VEGF-C expression of primary cancer and mediastinal lymph nodes metastasis.
      CONCLUSIONS: Serum VEGF-C level has close correlation with VEGF-C expression of
      primary cancer, lymphangiogenesis of primary cancer/mediastinal lymph nodes,
      mediastinal lymph nodes metastasis status and patient's survival rate. Serum VEGF
      C level is possible to be used as prognostic factor on lung cancer.

PMID- 20797327
TI  - [Expression and clinical significance of MTA1 in non-small cell lung cancer.].
AB  - BACKGROUND: Metastasis-associated gene 1 (MTA1 ) has been studied deeply recently
      as a tumor infiltration and metastasis gene. It was expressed in many tumor cell
      line and was correlated with tumor infiltration and metastasis. The aim of this
      study is to investigate the relationship between the expression of MTA1 and
      invasion and metastasis of non-small cell lung cancer (NSCLC). METHODS: Optimal
      conditions of nested reverse transcription polymerase chain reaction (RT-PCR)
      were found out; then the expression of MTA1 mRNA in 42 samples of primary
      carcinoma tissues, paracancerous tissues, normal tissues and corresponding lymph
      nodes were compared with 20 lung innocence tissues at semi-quantitative level and
      the results were compared with clinical pathologic data. RESULTS: Average
      expression of the MTA1 gene in NSCLC primary carcinoma tissue (1.50+/-0.26) and
      lymph nodes with metastasis (1.88+/-0.35) was remarkably higher than that in
      normal tissue (1.02+/-0.17) and lung innocence tissue (0.90+/-0.15) (P <0.01).
      Average expression of the MTA1 gene in NSCLC primary carcinoma tissue (1.50+/
      0.26) was significantly higher than that in paracancerous tissue (1.09+/-0.16).
      Average expression of the MTA1 gene in lymph nodes with metastasis (1.88+/-0.35)
      was significantly higher than that in those without metastasis (1.40+/-0.36) (P
      <0.01). The frequency of MTA1 overexpression in NSCLC tissue was closely
      correlated with clinical staging, T staging and N staging; the frequency of MTA1
      overexpression was 45.2% (19/42) in NSCLC tissue. The frequency of MTA1
      overexpression was 84.2% (16/19) in lymph nodes with metastasis. The expression
      level of MTA1 gene in cancer tissues was not related to age, gender of the
      patients and type of tumor. CONCLUSIONS: Our data suggests that the
      overexpression of the MTA1 gene correlates with invasion and metastasis of NSCLC.
      A high expression of MTA1 mRNA may be a potential indicator for assessing the
      malignancy and metastasis of NSCLC.

PMID- 20797328
TI  - [Cryosurgery combined with Iodine-125 seed implantation in the treatment of
      unresectable lung cancer.].
AB  - BACKGROUND: As many lung cancer patients lose surgical possibility, it is
      important to explore new treatments to improve prognosis. The study is to observe
      adverse reactions and therapeutic effects of cryosurgery combined iodine-125
      seeds implantation in treating advanced lung cancer patients. METHODS: One
      hundred forty unresectable pulmonary cancer patients received percutaneous
      cryosurgery and iodine-125 implantation under CT guidance. Patients were followed
      up 1 year, with CT scan, therapeutic effect, complications and survival time
      monitoriy. RESULTS: The one hundred forty patients successfully received
      cryosurgery combined with iodine-125 seed implantation and one-year follow-up.
      The patients with 6 m posttreatment had complete remission (CR) of 93.4%, partial
      remission (PR) of 70.1%, stable disease (SD) of 7.4%, and progressive disease
      (PD) of 5.7%. The half-year and one-year survival rates were 94.3% and 65.7%
      respectively. The average KPS was improved from 66.9 to 76.3. CONCLUSIONS:
      Cryosurgery combined with iodine-125 seed implantation is effective in treating
      unresectable lung cancer, providing a promising treatment protocol for
      unresectable lung cancer patients.

PMID- 20797329
TI  - [A study on the relationship between RRM1 single nucleotide polymorphisms and
      clinical characteristics in lung cancer patients.].
AB  - BACKGROUND: Gemcitabine is representative agent for chemotherapy in non-small
      cell lung cancer (NSCLC). The aims of this study are to investigate the single
      nucleotide polymorphism (SNP) of the gene such as ribonucleotide reductase
      subunit M1 (RRM1 ), which is the molecular target of gemcitabine, probably
      contribute to the resistance progress. METHODS: Allele-specific primers (wild,
      mutant and the same antisense primers) were designed according to the sequence of
      RRM1 . The allelotyping of RRM1 promoter polymorphisms was conducted via SYBR
      Green I real-time PCR using genomic DNA obtained from peripheral WBC of 110 lung
      cancer cases and 40 cases of healthy subjects and the relationship of genotype
      and characteristic, response and survival time of lung cancer patients were also
      analyzed. RESULTS: Using Fluorescence PCR, the occurrence of allele A genotype at
      the promoter 37 site is 32 percent and 30 percent separately in lung cancer
      patients and healthy individuals. There were no relations between AA frequency
      and general characteristic of lung cancer patients such as sex, pathologic,
      clinical stage, response rate and over-all survival time in patients receiving
      gemcitabine reagents (P >0.05). CONCLUSIONS: The specific primer real-time PCR
      can detect the SNP of RRM1 gene.

PMID- 20797330
TI  - [Expression and clinical significance of ADAM8 and CEA in serum of patients with
      non-small cell lung cancer.].
AB  - BACKGROUND: Lung cancer is one of the most common cancers in the world, whose
      mortality is at the first place in all malignant tumors. This study is to
      investigate the diagnostic value of ADAM8 and CEA in serum of non-small cell lung
      cancer patients. METHODS: The serum levels of ADAM8 were assayed by ELISA in 62
      NSCLC patients, 27 benign palmonary lesions and 32 healthy subjects as control.
      The serum level of CEA were assayed by radioimmunoassay. RESULTS: The serum level
      of ADAM8 and CEA in group of NSCLC were both remarkably higher than those in lung
      benign lesions and normal controls (P <0.01), without significant difference
      between benign palmonary lesions and normal controls (P >0.05). There was no
      significant difference between adenocarcinoma and squamous cell carcinoma in
      serum ADAM8 level (P >0.05). The serum level of CEA in adenocarcinoma were
      significantly higher than that in squamous cell carcinoma (P <0.05). The serum
      level of ADAM8 and CEA in NSCLC with stages III-IV were both remarkably higher
      than those with stages I-II (P <0.01). The level of ADAM8 and CEA in NSCLC with
      lymph node metastasis positive were both higher than those of negative (P <0.01).
      The diagnostic sensitivity of ADAM8 and CEA for NSCLC was 77.4% and 71.0%
      respectively, and the specificity was 90.6% and 84.4% respectively. The combined
      detection of ADAM8 and CEA could improve the sensitivity to 91.9%, but the
      specificity decreased to 75.0%. CONCLUSIONS: The overexpression of ADAM8 in serum
      of NSCLC patients indicates that ADAM8 is related to the development of NSCLC;
      Combined detection of ADAM8 and CEA is helpful for the diagnosis of NSCLC.

PMID- 20797331
TI  - [Expression and significance of PTEN and nm23-H1 in the metastasis of non-small
      cell lung cancer.].
AB  - BACKGROUND: It has been proven that PTEN and nm23-H1 genes were the tumor
      metastasis suppressor genes. Up to now, most of studies are aim at basic
      research. The aim of this study is to explore the level of expression of PTEN and
      nm23-H1 protein in non-small cell lung cancer and their relationship to the
      clinical significance of non-small cell lung cancer. METHODS: An
      immunohistochemical method was used to detect the expression of PTEN and nm23-H1
      protein in 60 cases of non-small cell lung cancer. RESULTS: In the groups with
      and without lymph nodes metastasis, the positive rates of PTEN protein expression
      were 41.94% and 79.31% respectively. The difference between them was significant
      (P <0.01). The rates of positive expression of nm23-H1 protein were 45.16% and
      82.76% respectively. The difference between them also was significant (P <0.01).
      The expression of PTEN was relatively consistent with that of nm23-H1 (Kappa
      =0.436 6, Z =3.390 5, P <0.01). CONCLUSIONS: The expressions of PTEN and nm23-H1
      in NSCLC were closely related to lymph nodes metastasis. Combining detection of
      these two proteins might be more helpful for evaluating lymph nodes metastasis
      and predicting the prognosis.

PMID- 20797332
TI  - [The expression and clinical significance of heparanase in non-small cell lung
      cancer.].
AB  - BACKGROUND: It has been proven that heparanase played an important role in
      tumorigenesis. The aim of this work is to investigate the level of expression of
      heparanase protein in non-small cell lung cancer (NSCLC) and to explore the
      relationship between heparanase expression and NSCLC histological types and
      prognosis. METHODS: Immunohistochemical method was used to detect the heparanase
      expression in the routinely paraffin-embedded sections of surgical specimen of 66
      cases with NSCLC and 15 ones with normal lung tissues. RESULTS: Heparanase was
      highly expressed in lung cancer tissues (74.2%) while negative in epithelia of
      normal lung tissues. The expression of heparanase was significantly correlated
      with TNM stage (P =0.042) and lymphatic metastasis (P =0.005). The patients with
      positive heparanase expression had a significantly shorter survival rate than
      those with negative heparanase expression (P =0.025). CONCLUSIONS: Heparanase has
      more expression in NSCLC than normal lung tissues. It was correlated with TNM
      stage and lymphatic metastasis and prognosis of NSCLC. However, heparanase
      expression is not an independent prognostic factor.

PMID- 20797334
TI  - [Progress of traditional Chinese medicine and western treatment for elderly
      advanced lung cancer.].

PMID- 20797333
TI  - [The role and significance of serum SYK and VEGF-C in metastasis of the lymph
      nodes of pulmonary adenocarcinoma.].
AB  - BACKGROUND: Lung cancer has become one of the most dangerous malignant tumor in
      the world nowadays, whose pathogenesis is complex involving multi-genes and multi
      elements. In this study, we try to explore the values of serum SYK and vascular
      endothelial growth factor-C (VEGF-C) in lymph node metastasis of lung
      adenocarcinoma. METHODS: Serum SYK and VEGF were examined in 160 lung
      adenocarcinoma patients with various metastasis lesions and 40 healthy volunteers
      by ELISA. RESULTS: The serum SYK level of the lung adenocarcinoma patients were
      remarkably lower than those of normal persons (P <0.05); The SYK level decreased
      while the lymph nodes area increased along with their metastasis (P <0.05), and
      the serum VEGF-C level were remarkably higher than those of healthy objects (P
      <0.05). The VEGF-C level increased with the increase of lymph nodes metastasis (P
      <0.05). For the serum level of SYK and VEGF-C, there was no statistical
      difference in sex and age (P <0.05). Negative correlation was found between SYK
      and VEGF-C (r =0.650, P <0.05). CONCLUSIONS: The serum level of SYK and VEGF-C
      are closely related to the lymph nodes metastasis of lung adenocarcinoma.
      Combination detection of SYK and VEGF-C might be helpful for the predict of lymph
      nodes metastasis of lung adenocarcinoma.

PMID- 20797335
TI  - [A novel marker DMP1 for non-small-cell lung carcinomas.].

PMID- 20797336
TI  - [Sleeping beauty transposion and its potential applications in cancer research.].

PMID- 20797337
TI  - [Advance in the study of the Leptin and its receptors ob-R effect on lung
      cancer.].

PMID- 20797338
TI  - [The investgation of prophylactic cranial irradiation forlocally advanced non
      small cell lung cancer.].

PMID- 20797339
TI  - [Minimal invasive treatment for peripheral non small cell lung carcinoma.].

PMID- 20797340
TI  - [The chemotherapeutic progress of advanced non-small cell lung cancer--from 2008
      ASCO.].

PMID- 20797341
TI  - [Application of micro-fluid chip in detecting micrometastasis of non-small-cell
      lung cancer.].

PMID- 20797342
TI  - Embryo biotechnology in the dog: a review.
AB  - Canine embryos are a scarce biological material because of difficulties in
      collecting in vivo-produced embryos and the inability, to date, to produce canine
      embryos in vitro. The procedure for the transfer of in vivo-produced embryos has
      not been developed adequately, with only six attempts reported in the literature
      that have resulted in the birth of 45 puppies. In vitro, the fertilisation rate
      is particularly low ( approximately 10%) and the incidence of polyspermy
      particularly high. So far, no puppy has been obtained from an in vitro-produced
      embryo. In contrast, cloning of somatic cells has been used successfully over the
      past 4 years, with the birth of 41 puppies reported in the literature, a yield
      that is comparable to that for other mammalian species. Over the same period,
      canine embryonic stem sells and transgenic cloned dogs have been obtained. Thus,
      the latest reproductive technologies are further advanced than in vitro embryo
      production. The lack of fundamental studies on the specific features of
      reproductive physiology and developmental biology in the canine is regrettable in
      view of the increasing role of dogs in our society and of the current demand for
      new biological models in biomedical technology.

PMID- 20797343
TI  - Development of novel strategies for the isolation of piglet testis cells with a
      high proportion of gonocytes.
AB  - Gonocytes have germline stem cell potential and are present in the neonatal
      testis, comprising 5-10% of freshly isolated testis cells. Maximising the number
      and proportion of gonocytes among freshly isolated testis cells will greatly
      facilitate their subsequent purification and in vitro study and manipulation.
      Seven experiments were conducted to evaluate the effects of multiple factors on
      the efficiency of testis cell isolation from neonatal pigs. We found that the use
      of a lysis buffer led to elimination of erythrocytes without adversely affecting
      testis cell isolation. Approximately ninefold as many live cells could be
      harvested by enzymatic digestion of testis tissues compared with mechanical
      methods. Digestion with collagenase-hyaluronidase-DNase followed by trypsin
      resulted in the highest recovery of live cells. However, the proportion of
      gonocytes ( approximately 7%) did not differ between the mechanical and enzymatic
      methods of testis cell isolation. Pretreatment of the tissue with cold enzymes
      increased the recovery of live testis cells. New strategies of combining a gentle
      enzymatic digestion with two rounds of vortexing resulted in the isolation of
      testis cells with very high gonocyte proportion. The efficiency of these novel
      methods could be further optimised to collect testis cells with a gonocyte
      proportion of approximately 40%. This novel three-step testis cell isolation
      strategy can be completed within 1 h and can harvest approximately 17 x 10(6)
      live gonocytes per g testis tissue. Therefore, in addition to elucidating the
      effects of several factors on testis cell isolation, we developed a novel
      strategy for the isolation of testis cells that yielded approximately 40%
      gonocytes in the freshly isolated cells (i.e. four- to eight-fold higher than the
      proportions obtained using current strategies). This strategy has instant
      applications in the purification of gonocytes.

PMID- 20797344
TI  - Inherited sperm head abnormalities in the B10.M mouse strain.
AB  - Examination of sperm head morphology is one of the requisite tests of the
      functional capacity of semen in reproduction. In the present study, genetic
      effects on morphological sperm head abnormalities in mice were investigated. The
      frequency of abnormal spermatozoa was determined in 17 inbred mouse strains and
      it was found that strain B10.M had the highest frequency of abnormal spermatozoa
      (44.7%). Segregation analysis was then used to show that the abnormal sperm
      phenotype in B10.M mice was inherited. The results indicated that this sperm
      abnormality was controlled by two distinct recessive alleles. It is proposed that
      the high frequency of the heritable abnormal sperm phenotype in the mouse B10.M
      strain explains the subfertility of this strain, as evidenced by its reduced
      litter size.

PMID- 20797345
TI  - Effect of oxygen tension and serum during IVM on developmental competence of
      bovine oocytes.
AB  - With an aim to improve the in vitro production of bovine embryos, the present
      study investigated the effect of serum and oxygen tension during IVM on oocyte
      developmental competence. Four experimental groups were evaluated: G1, 10%
      oestrus cow serum (OCS) with 20% O(2); G2, 0.1% polyvinyl alcohol (PVA) with 20%
      O(2); G3, 10% OCS with 5% O(2); and G4, 0.1% PVA with 5% O(2). The proportion of
      MII oocytes, blastocyst rates and total cell number were not affected (P > 0.05)
      when the OCS was replaced with PVA under 5% O(2), whereas a higher (P < 0.05)
      blastocyst rate and total cell number were found with OCS compared with PVA under
      20% O(2). The apoptosis index was lower in blastocysts from oocytes matured with
      PVA under 5% O(2) (G4) compared with other groups (G1, G2 and G3), but no
      differences (P > 0.05) were found in maturation and blastocyst rates. Significant
      differences were found in the amount of specific transcripts in oocytes matured
      under different conditions. In conclusion maturation with PVA and 5% O(2)
      provides an efficient in vitro culture condition for the maturation of bovine
      oocytes.

PMID- 20797346
TI  - Anti-Mullerian hormone: a predictive marker of embryo production in cattle?
AB  - In cattle, the embryo production rate after superovulation varies between
      individuals and is difficult to predict. Recently, we proposed that anti
      Mullerian hormone (AMH) plasma levels measured before treatment can help predict
      superovulatory responses. To establish whether blood measurement of AMH can help
      predict the number of embryos produced by a given cow after superovulation, data
      collected over 4 years from 45 dairy cows submitted to repeated embryo production
      were analysed in a retrospective study. A high within-animal repeatability (0.38
      and 0.36) and a strong effect of the father of the donor cow (P < 0.01) were
      observed for the numbers of collected and transferable embryos, respectively. AMH
      concentration, measured in the plasma of donor cows during first lactation and
      several months before the start of the embryo production campaigns, was found to
      be highly correlated with the maximal number of collected (P < 0.0001) and
      transferable (P < 0.01) embryos per cow. In conclusion, the capacity of embryo
      production is a repeatable and probably heritable trait in the cow, and blood
      measurement of AMH in potential donor cows could be of value in determining a
      cow's intrinsic capacity to produce transferable embryos.

PMID- 20797347
TI  - Positive effect of FSH but not LH on early development of the dominant follicle
      in mares.
AB  - The effects of FSH, LH or both on follicular growth and intrafollicular free
      insulin-like growth factor (IGF)-1 and oestradiol were investigated in mares
      after the beginning of deviation (largest follicle >/= 20 mm; Hour 0). A single
      treatment with a gonadotropin-releasing hormone antagonist (acyline) was given at
      Hour 3 to suppress the concentrations of FSH and LH. Five groups (n = 5 mares per
      group) were evaluated in the present study: (1) control; (2) acyline treated; (3)
      acyline + recombinant equine (re) FSH treated; (4) acyline + reLH treated; and
      (5) combined acyline + reFSH + reLH treated. Beginning at Hour 3, reFSH and reLH
      were given at 6-h intervals in eight decreasing or increasing doses,
      respectively. The reFSH and reLH prevented the acyline-induced decreases in FSH
      and LH, respectively. Diameters and concentrations of intrafollicular free IGF-1
      and oestradiol of the two largest follicles at Hour 48 did not differ
      significantly between the control and acyline + FSH groups, but were reduced (P <
      0.05) similarly in the acyline and acyline + LH groups. The combination of reFSH
      and reLH was no more effective than reFSH alone. The results demonstrate a role
      for FSH but not LH in the growth of the largest follicle and intrafollicular
      concentrations of free IGF-1 and oestradiol during the 48 h after the beginning
      of deviation in mares.

PMID- 20797348
TI  - Relationship between cumulus cell apoptosis, progesterone production and porcine
      oocyte developmental competence: temporal effects of follicular fluid during IVM.
AB  - The objective of the present study was to determine the temporal effects of sow
      follicular fluid (FF) in vitro on cumulus cell viability and function, as well as
      oocyte nuclear and cytoplasmic maturation. Cumulus-oocyte complexes (COCs)
      recovered from the ovaries of prepubertal pigs were matured in medium with (+FF)
      or without (-FF) follicular fluid for the first 22 h of IVM. At 22 h of IVM, each
      group of COCs was then transferred to medium with or without FF and matured for
      another 22 h, forming four treatment groups (-FF/-FF, -FF/+FF, +FF/-FF and
      +FF/+FF). The concentration of progesterone in spent IVM medium and the incidence
      of cumulus cell apoptosis in individual COCs were determined at 22 and 44 h of
      IVM. Cumulus expansion was also recorded at 44 h of IVM. Finally, the ability of
      oocytes to complete meiosis to the MII stage and form blastocysts after IVF and
      embryo culture was assessed. Maturation with FF for part or the whole of IVM
      increased cumulus expansion and progesterone production and decreased the
      incidence of cumulus cell apoptosis compared with the -FF/-FF group (P < 0.05).
      The changes were greatest for the +FF/+FF group and intermediate for the -FF/+FF
      and +FF/-FF groups. Regression analysis revealed a negative association between
      cumulus cell progesterone production and the incidence of cumulus cell apoptosis
      (P < 0.001). Meiotic maturation was enhanced when FF was present during the first
      half of IVM. Oocytes matured in the presence of FF during the first and/or second
      half of IVM displayed an increased ability to form blastocysts compared with the 
      FF/-FF group (P < 0.05). The extent of the increase was similar for all FF
      supplemented groups. The results show that FF exerts several beneficial effects
      at different times during IVM and suggest that a major role of FF is to provide
      protection from oxidative stress. We propose that the incidence of cumulus cell
      apoptosis in COCs must be kept below a certain threshold to ensure adequate
      functionality, including steroidogenic activity, is maintained for the
      acquisition of oocyte developmental competence.

PMID- 20797349
TI  - Temporal relationships of the LH surge and ovulation to echotexture and power
      Doppler signals of blood flow in the wall of the preovulatory follicle in
      heifers.
AB  - Changes in echotexture and blood flow in the wall of preovulatory follicles in
      heifers were studied in relation to the LH surge and ovulation in gonadotrophin
      releasing hormone-induced (n = 7; Experiment 1) and spontaneous (n = 8;
      Experiment 2) ovulators. Ultrasonographic examinations and blood sampling were
      performed either every hour (Experiment 1) or every 6 h (Experiment 2). The
      interval from LH peak to ovulation in induced and spontaneous ovulators was 27.1
      +/- 0.3 and 34.5 +/- 1.5 h, respectively. Follicle diameter did not increase
      between the LH peak and ovulation. In the induced ovulators, serration of the
      stratum granulosum was detected in one (14%), two (29%), three (43%) and four
      (57%) heifers at 4, 3, 2 and 1 h before ovulation, respectively. An initial
      increase in blood flow (P < 0.001) encompassed the LH peak in both experiments.
      In the induced ovulators, blood flow increased (P < 0.02) to maximum 3 h after
      the LH peak, maintained a plateau for 5 h, decreased (P < 0.05) between 9 and 14
      h, increased (P < 0.05) again between 19 and 21 h and then decreased (P < 0.01)
      between 25 and 26 h (1 h before ovulation). The biphasic increase and decrease in
      blood flow and serration of the granulosum in the wall of the preovulatory
      follicle in cattle are novel findings.

PMID- 20797350
TI  - Immunohistochemical study of the ubiquitin-nuclear factor-kB pathway in the
      endometrium of the baboon (Papio anubis) with and without endometriosis.
AB  - The aim of the present study was to conduct a semiquantitative
      immunohistochemical investigation into the levels of intermediary proteins within
      the nuclear factor (NF)-kappaB pathway throughout the menstrual cycle in a non
      human primate, namely the baboon (Papio anubis), with and without endometriosis.
      Formalin-fixed eutopic (n = 2-4) and ectopic (n = 6-7) endometrial tissues from
      baboons at the mid-luteal phase were embedded in paraffin and examined for NF
      kappaB pathway components (i.e. IkappaB kinase (IKK) alpha, IKKbeta,
      phosphorylated (phospho-) IkappaBalpha and phospho-NF-kappaB p65 subunit),
      ubiquitin, 19S proteasome and the NF-kappaB activator tumour necrosis factor
      (TNF)-alpha. Similarly, endometrial tissues from baboons at the late follicular,
      mid-luteal and menses phase (n = 2-4) were investigated to determine the levels
      of these proteins throughout the menstrual cycle. Cytoplasmic stromal IKKalpha
      and glandular 19S proteasome immunostaining was elevated in the ectopic
      endometrium, whereas levels of ubiquitin, phospho-p65, IKKbeta, TNF-alpha and
      nuclear 19S proteasome were similar in the eutopic and ectopic endometrium. A
      significant decrease in phospho-IkappaBalpha nuclear immunostaining was observed
      within glandular cells of the ectopic endometrium. In the eutopic endometrium,
      IKKalpha, ubiquitin and 19S proteasome immunostaining was elevated in different
      phases of the menstrual cycle, whereas levels of phospho-p65, IKKbeta, phospho
      IkappaBalpha and TNF-alpha remained unchanged. We have demonstrated that, in the
      baboon endometriosis model, levels of IKKalpha immunostaining are elevated,
      whereas those of phospho-IkappaBalpha are reduced, consistent with the hypothesis
      that excessive NF-kappaB activity plays a role in reducing ectopic endometrial
      apoptosis, which contributes to the pathophysiology of endometriosis. Further
      studies are required to confirm a causal association between elevated IKKalpha
      levels and reduced endometrial apoptosis.

PMID- 20797351
TI  - Flow-sorted ram spermatozoa are highly susceptible to hydrogen peroxide damage
      but are protected by seminal plasma and catalase.
AB  - To determine whether flow sorting increased the susceptibility of spermatozoa to
      reactive oxygen species (ROS), ram semen was either diluted with Tris medium (100
      x 10(6) spermatozoa mL(-1); D) or highly diluted (10(6) spermatozoa mL(-1))
      before being centrifuged (DC) at 750g for 7.5 min at 21 degrees C or flow-sorted
      (S) before cryopreservation. Thawed spermatozoa were resuspended in graded
      concentrations of hydrogen peroxide to induce oxidative stress. In Experiment 1,
      following exposure to 30 or 45 muM hydrogen peroxide (H(2)O(2)), the total
      motility (%) of DC (41.0 +/- 7.3 or 25.7 +/- 6.7, respectively) and S spermatozoa
      (33.8 +/- 6.3 or 20.1 +/- 6.3, respectively) was lower (P < 0.001) than that of D
      spermatozoa (58.7 +/- 5.6 or 44.5 +/- 6.7, respectively). In Experiment 2,
      supplementation of samples containing H(2)O(2) with catalase (150 IU mL(-1)) or
      seminal plasma proteins (4 mg protein per 10(8) spermatozoa) negated oxidative
      stress, resulting in comparable values to samples receiving no H(2)O(2)in terms
      of the proportion of spermatozoa with stable plasmalemma (as determined using
      merocyanine-540 and Yo-Pro-1) in the D and S groups, the proportion of viable,
      acrosome-intact spermatozoa (as determined by fluorescein isothiocyanate and
      propidium iodide staining) in the D group and the motility of control (undiluted)
      and S spermatozoa. Neither H(2)O(2) nor sperm type (i.e. D, DC or S) had any
      effect on intracellular concentrations of ROS. These results show that flow
      sorting increases the susceptibility of spermatozoa to ROS, but the inclusion of
      anti-oxidants or seminal plasma as part of the sorting protocol improves
      resistance to oxidative stress.

PMID- 20797352
TI  - Survival and apoptosis rates after vitrification in cryotop devices of in vitro
      produced calf and cow blastocysts at different developmental stages.
AB  - Two experiments were designed to determine the ability of in vitro-cultured
      blastocysts at different stages of development to survive the vitrification
      procedure using cryotop devices. Day 7 and Day 8 embryos were classified as non
      expanded, expanded or hatching and/or hatched blastocysts. In the first
      experiment, we examined the survival rate of vitrified-warmed blastocysts after 3
      h incubation in synthetic oviducal fluid (SOF) medium. In the second experiment,
      vitrified-warmed blastocysts were evaluated using the terminal
      deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling
      (TUNEL) technique to detect nuclei with damaged DNA. In both experiments, results
      for cow and calf blastocysts were compared. No differences in survival rates were
      observed after vitrification of Day 8 expanded (52.4%) and hatched (50%) cow
      blastocysts or Day 8 expanded (54.5%) and hatched (59.4%) calf blastocysts. When
      embryos were vitrified on Day 7, survival rates of 78.4% and 66.7% were observed
      after warming expanded and hatched cow blastocysts, respectively, compared with
      rates of 80% and 76.9%, respectively, for calf blastocysts. Lowest survival rates
      were recorded for non-expanded blastocysts (26%-54%) compared with the other
      developmental stages, particularly those vitrified at Day 8 (</=40%). The DNA
      integrity index obtained after vitrification-warming was comparable to that for
      control fresh blastocysts, regardless of the length of embryo culture, the
      developmental stage of the embryo or the source of the oocytes. Our findings
      suggest that the cryotop vitrification method is particularly useful for the
      cryopreservation of blastocysts presenting with a high degree of expansion
      (expanded or hatched blastocysts), particularly when vitrification is performed
      after 7 days of in vitro embryo culture.

PMID- 20797353
TI  - Neonatal superior ovarian nerve transection inhibits follicle development by
      enhancing follicular atresia and suppressing granulosa cell proliferation in
      rats.
AB  - The ovarian sympathetic nerves participate in the regulation of mammalian ovarian
      function, but it is still not known whether the neonatal ovarian sympathetic
      nerve is involved in follicular development and related mechanisms. In the
      present study, the superior ovarian nerve (SON) of the neonatal rat was
      transected on postnatal day (PD) 2, and follicle development, ovarian hormone
      secretion, ovulation rate, granulosa cell proliferation and apoptosis were
      analysed on PD 30 and PD 90. The results demonstrate that SON transection
      decreases follicle number and size, reduces ovulation induced by gonadotrophin
      and enhances follicular atresia. Bromodeoxyuridine (BrdU) and cleaved caspase-3
      immunohistochemistry staining provide evidence that SON transection inhibits
      granulosa cell proliferation and promotes granulosa cell apoptosis. In addition,
      SON transection increases serum oestradiol levels, but has no influence on serum
      progesterone levels. These results suggest that the sympathetic nerve supply to
      the ovaries is important in regulating follicle development and ovary function.
      These results are critical for further understanding of the neuroendocrine
      regulation of ovary development and function, although the mechanism needs to be
      elucidated in future studies.

PMID- 20797354
TI  - Ultrasonographically documented early pregnancy loss in an Asian elephant
      (Elephas maximus).
AB  - Early embryonic resorption or fetal loss is known to occur occasionally in
      captive elephants; however, this has mostly been reported anecdotally. The
      present study documents the case of a 24-year-old, multiparous Asian elephant cow
      that suffered embryonic death and resorption at around 18 weeks of gestation.
      From ovulation onwards, this female was sonographically examined 58 times. Blood
      was collected twice weekly for progestagen determination via enzyme immunoassay.
      On Day 42 after ovulation, a small quantity of fluid was detected in the uterine
      horn, which typically indicates the presence of a developing conceptus. Repeated
      inspections followed what appeared to be a normal pregnancy until Day 116.
      However, on Day 124, signs of embryonic life were absent. Progestagen
      concentrations started declining two weeks later, reaching baseline levels one
      month after embryonic death. Retrospectively, ultrasound examination revealed
      several abnormalities in the uterine horn. Besides an existing leiomyoma,
      multiple small cystic structures had formed in the endometrium at the
      implantation site and later in the placenta. These pathological findings were
      considered as possible contributors to the early pregnancy failure. PCR for
      endotheliotropic elephant herpes virus (EEHV) (which had occurred previously in
      the herd) as well as serology for other infectious organisms known to cause
      abortion in domestic animals did not yield any positive results. Although no
      definitive reason was found for this pregnancy to abort, this
      ultrasonographically and endocrinologically documented study of an early
      pregnancy loss provides important insights into the resorption process in Asian
      elephants.

PMID- 20797355
TI  - Barriers to comorbidity service delivery: the complexities of dual diagnosis and
      the need to agree on terminology and conceptual frameworks.
AB  - This paper draws from a literature review commissioned as part of a larger
      project evaluating comorbidity treatment service models, which was funded by the
      Australian Government Department of Health and Ageing as part of the National
      Comorbidity Initiative. The co-occurrence of mental health and substance use
      disorders (comorbidity) is a common and complex problem. This paper outlines
      conceptual and practical complexities and barriers associated with comorbidity
      treatment service delivery, particularly around the variable nature of
      comorbidity, and the impacts of the separation of the mental health (MH) and
      alcohol and other drug (AOD) sectors with their differing institutional cultures,
      aetiological concepts, philosophical underpinnings, educational requirements,
      administrative arrangements, and screening and treatment approaches. Issues
      pertaining to the lack of consistent definitions and conceptual frameworks for
      comorbidity are discussed, particularly in relation to the reported lack of
      communication, collaboration, and linkages between the sectors. It is suggested
      that the adoption of consistent terminology and conceptual frameworks may provide
      a valuable step towards consistency in service provision and research and could
      lead to improved capacity to address the many issues relating to comorbidity
      service provision and treatment efficacy.

PMID- 20797356
TI  - Medically-managed Hospital in the Home: 7 year study of mortality and unplanned
      interruption.
AB  - BACKGROUND: Hospital in the Home (HIH) research is characterised by small samples
      in new programs. We sought to examine a large number of consecutive HIH
      admissions over many years in an established, medically-managed HIH service in to
      determine whether: (1) HIH is a safe and effective method of delivering acute
      hospital care, under usual operating conditions in an established unit; and (2)
      what patient, condition and treatment variables contribute to a greater risk of
      failure. METHODS: A survey of all patients admitted to a medically-managed HIH
      unit from 2000-2007. RESULTS: A total of 3423 admissions to HIH were examined. Of
      these 2207 (64.5%) were admitted directly into the HIH from Emergency Department
      or rooms, with the remainder admitted from hospital wards. A total of 26,653 HIH
      bed days were delivered. with a mean of 9.3 nursing visits and 4.1 medical visits
      per admission. A total of 143 patients (4.2%) required an interruption via an
      unplanned return to hospital; 106(3.1%) did not subsequently return to HIH. The
      commonest reason for unplanned returns to hospital were: no clinical improvement;
      cardiac conditions; fevers; breathlessness and pain. Patients over the age of 50,
      and those receiving intravenous antibiotic therapy, were more likely to require a
      return to patients died unexpected mortality rate of 0.15%. CONCLUSION: This
      sample of HIH patients is five time the number of HIH patients ever enrolled in
      randomised trials studies of this area. Further, outcomes were achieved in
      'ordinary' working conditions over a long time period. Care was completed without
      interruption (return to hospital) in 95.8% of all episodes. Interruption was
      associated with patients referred from impatient wars, older patients who were
      treated with intravenous antibiotics, Patients referred from Emergency
      Departments experienced fewer interruptions. Nursing home residents were no more
      likely to required an interruption to their HIH care.

PMID- 20797357
TI  - The reported benefits of telehealth for rural Australians.
AB  - OBJECTIVE: A literature review was conducted to identify the reported benefits
      attributed to telehealth for people living and professionals working in rural and
      remote areas of Australia. DATA SOURCES: Scopus and relevant journals and
      websites were searched using the terms: telemedicine, telehealth, telepsychiatry,
      teledermatology, teleradiology, Australia, and each state and territory.
      Publications since 1998 were included. STUDY SELECTION: The initial search
      resulted in 176 articles, which was reduced to 143 when research reporting on
      Australian rural, regional or remote populations was selected. DATA SYNTHESIS: A
      narrative review was conducted using an existing 'benefits' framework. Patients
      are reported to have benefited from: lower costs and reduced inconvenience while
      accessing specialist health services; improved access to services and improved
      quality of clinical services. Health professionals are reported to have benefits
      from access to continuing education and professional development; provision of
      enhanced local services; experiential learning, networking and collaboration.
      DISCUSSION: Rural Australians have reportedly benefited from telehealth. The
      reported improved access and quality of clinical care available to rural
      Australians through telemedicine and telehealth may contribute to decreasing the
      urban-rural health disparities. The reported professional development
      opportunities and support from specialist through the use of telehealth may
      contribute to improved rural medical workforces recruitment and retention.

PMID- 20797358
TI  - Readmission to an acute psychiatric unit within 28 days of discharge: identifying
      those at risk.
AB  - OBJECTIVE: To examine factors that could help identify those most at risk of
      readmission to an acute psychiatric in-patient unit within 28 days of a
      discharge. METHOD: A detailed file audit was conducted comparing 54 consecutive
      patients who had been readmitted within 28 days of discharge with 61 patients,
      chosen at random, who had not been readmitted during the same period. RESULTS:
      Readmission within 28-days of discharge was associated with having been admitted
      in the previous year (P = 0.004), receiving the Disability Support Pension (P =
      0.015), not having a discharge plan sent to the patient's GP on discharge from
      the index admission (P = 0.05), receiving follow-up by the mental health team
      within 7 days of discharge (P = 0.007) and being unemployed (P = 0.015).
      CONCLUSIONS: Targeting those with previous admissions for focussed discharge
      planning may help organisations reduce the numbers of unnecessary early
      readmissions.

PMID- 20797359
TI  - 'Hands on, Hands off': a model of clinical supervision that recognises trainees'
      need for support and independence.
AB  - RATIONALE: This article presents a study of junior doctor supervision at a rural
      hospital. The objective of the present study was to gain insight into the types
      of supervision events experienced, the quality of supervisory relationships, the
      frequencies of supervision contact in a rural hospital setting, and the
      implications of these factors for supervision practice. METHODS: A cohort of
      junior doctors was asked to provide in-depth information about their interactions
      with their supervisors and other relevant clinical colleagues. The information
      was filled in on diary sheets to capture the nature, focus and quality of the
      cohort's supervision experiences over 2 weeks. The information also covered
      frequency and types of supervisory contacts. RESULTS: The quantitative data
      reveals that supervisory events occur predominantly as part of ongoing patient
      care and rarely off-line as part of targeted supervisory practice. The
      qualitative data analysis reveals that junior doctors value supervisory support
      of two kinds: assistance from more senior clinicians who are expert in areas
      where trainees need help, and trust to act independently, without being
      abandoned. CONCLUSION: Supervision must be both structured and dynamic. Besides
      providing a regular forum for discussion and reflection, supervision must
      accommodate the variable needs of individual junior doctors and navigate between
      being hands-on and hands-off. Such dynamic approach is necessary to reassure
      junior doctors they are in a 'zone of safe learning' where they can act with
      adequate and flexible support and negotiate changes in supervisory attention.

PMID- 20797360
TI  - Rural health career pathways: research themes in recruitment and retention.
AB  - OBJECTIVE: This paper describes stages in the research literature related to
      recruitment and retention of health professionals to rural health careers. DATA
      SOURCES: Electronic databases accessed included Medline, CINAHL, Social Sciences
      and Humanities. Key search terms included 'high school', 'career choices',
      'rural', 'attachment', 'recruitment' and 'retention'. DATA SYNTHESIS: We
      identified four stages: (1) making career choices; (2) being attached to place;
      (3) taking up rural practice; and (4) remaining in rural practice. This is termed
      the 'rural pipeline'. However, as some stages of the 'rural pipeline' refer
      specifically to the medical profession, we propose an extension of the notion of
      the medical 'rural pipeline' to include other professions such as nursing,
      midwifery and allied health. CONCLUSIONS. Utilising the 'rural pipeline' as a
      template for medicine, nursing and allied health would strengthen current
      approaches to the recruitment and retention of professionals in rural areas and
      provide a consolidated evidence base that would assist in policy development to
      improve availability and service provision of the rural health workforce. Future
      research that utilises a multidisciplinary approach could explore how the role
      and relationship between place and identity shape needs of career choices and
      would provide important information to advance the practical aspects supporting
      rural health career pathways.

PMID- 20797361
TI  - Sustainable workforce reform: case study of Victorian nurse practitioner roles.
AB  - Nurse practitioner (NP) roles have been identified as a key strategy in the
      development of a sustainable and responsive health workforce. To date, the focus
      of research related to NP roles has been on implementation and short-term
      evaluation of aspects of NP care; however, little is known about the
      sustainability of NP roles. A major challenge for the healthcare sector is to
      demonstrate long-term outcomes of NP care and shift the research focus from
      individual NPs to the effectiveness of healthcare teams that incorporate NPs.
      This paper draws on a framework of the following domains of sustainability in
      primary care: political, institutional, financial-economic, workforce and client
      (or patient) and applies these domains to NP planning in the Victorian context.

PMID- 20797362
TI  - Returning to physiotherapy practice: the perspective of returners, potential
      returners and clinical supervisors.
AB  - The experience of returning to physiotherapy practice needs to be understood from
      the perspective of those who have returned to practice, those thinking of
      returning, and clinical supervisors who have worked with people that have
      returned to practice. A qualitative methodology using an interpretivist
      theoretical framework was utilised. Participants were selected using a
      combination of purposive and snowballing sampling techniques. Semi-structured
      interviews were conducted to determine the opinions of participants on returning
      to physiotherapy. Maternity and child-care were the main reason returners and
      potential returners took a break from physiotherapy. The main reason for
      returning to physiotherapy was because the returner wanted to rather than
      external factors such as financial hardship. Overall, the experience of returning
      to physiotherapy has been rewarding for returners and clinical supervisors.
      Returners and potential returners were highly motivated, keen to learn, and are
      willing to undertake a period of training to help them return to practice.
      However, there is only one programme available for returners to re-register as a
      physiotherapist and no refresher programmes are available. Returners, potential
      returners, and clinical supervisors thought that a structured re-registration or
      re-entry programme would need to be flexible to allow for returners' current
      needs, commitments, and career directions.

PMID- 20797363
TI  - The impact of nurses on patient morbidity and mortality - the need for a policy
      change in response to the nursing shortage.
AB  - CONTEXT: Workforce projections indicate that by 2012 there will be a shortfall of
      61,000 registered nurses in Australia. There is a growing body of evidence that
      links registered nurse staffing to better patient outcomes. PURPOSE: This article
      provides a comprehensive review of the research linking nurse staffing to patient
      outcomes at a time of growing shortages, highlighting that a policy response
      based on substituting registered nurses with lower skilled workers may have
      adverse effects on patient outcomes. METHOD: An electronic search of articles
      published in English using the Cumulative Index to Nursing and Allied Health
      Literature (CINAHL), Journals @ OVID and Medline was undertaken. FINDINGS: Robust
      evidence exists nationally and internationally that links nurse staffing to
      patient outcomes. Recent meta-analyses have found that there was a 3-12%
      reduction in adverse outcomes and a 16% reduction in the risk of mortality in
      surgical patients with higher registered nurse staffing. Evidence confirms that
      improvements in nurse staffing is a cost-effective investment for the health
      system but this is not fully appreciated by health policy advisors. CONCLUSIONS:
      An appropriate policy response demands that the evidence that patient safety is
      linked to nurse staffing be recognised. Policy makers must ensure there are
      sufficient registered nurses to guarantee patient safety.

PMID- 20797364
TI  - Public hospital bed crisis: too few or too misused?
AB  - * Increasing demand on public hospital beds has led to what many see as a
      hospital bed crisis requiring substantial increases in bed numbers. By 2050, if
      current bed use trends persist and as the numbers of frail older patients rise
      exponentially, a 62% increase in hospital beds will be required to meet expected
      demand, at a cost almost equal to the entire current Australian healthcare
      budget. * This article provides an overview of the effectiveness of different
      strategies for reducing hospital demand that may be viewed as primarily (although
      not exclusively) targeting the hospital sector - increasing capacity and
      throughput and reducing readmissions - or the non-hospital sector - facilitating
      early discharge or reducing presentations and admissions to hospital. Evidence of
      effectiveness was retrieved from a literature search of randomised trials and
      observational studies using broad search terms. * The principal findings were as
      follows: (1) within the hospital sector, throughput could be substantially
      improved by outsourcing public hospital clinical services to the private sector,
      undertaking whole-of-hospital reform of care processes and patient flow that
      address both access and exit block, separating acute from elective beds and
      services, increasing rates of day-only or short stay admissions, and curtailing
      ineffective or marginally effective clinical interventions; (2) in regards to the
      non-hospital sector, potentially the biggest gains in reducing hospital demand
      will come from improved access to residential care, rehabilitation services, and
      domiciliary support as patients awaiting such services currently account for 70%
      of acute hospital bed-days. More widespread use of acute care and advance care
      planning within residential care facilities and population-based chronic disease
      management programs can also assist. * This overview concludes that, in reducing
      hospital bed demand, clinical process redesign within hospitals and capacity
      enhancement of non-hospital care services and chronic disease management programs
      are effective strategies that should be considered before investing heavily in
      creating additional hospital beds devoid of any critical reappraisal of current
      models of care.

PMID- 20797365
TI  - The sustainability of Medical Morning Handover Reporting: adherence in a regional
      hospital.
AB  - BACKGROUND: The Medical Morning Handover Report is a form of clinical handover
      and is considered to be an essential mechanism for continuity of care and adverse
      event minimisation within a hospital environment. It is considered a significant
      Quality of Care activity recommended in Australian Medical Association clinical
      handover guidelines. The sustainability of such activities has not been reported.
      AIM: We aimed to assess the sustainability of Medical Morning Handover Reporting
      (MMHR) in the Department of Medicine at the Launceston General Hospital since its
      implementation in 2001. METHODS: We conducted a quality improvement survey
      amongst the medical staff (pre-graduate and post graduate medical faculties) to
      assess its sustainability since implementation in 2001. RESULTS: There were 30
      respondents of whom 19 attended MMHR daily, four attended weekly, and only five
      attended less than weekly. Attendance rates at MMHR were maintained from 2001 to
      2009 based on comparisons with previously conducted surveys. CONCLUSIONS: This
      study shows MMHR is sustainable and has evolved in format to incorporate advances
      in Health Information Technology. We believe adherence is dependent on providing
      leadership and structure to MMHR.

PMID- 20797366
TI  - An evaluation of a benchmarking initiative in extended treatment mental health
      services.
AB  - AIM: To evaluate the effectiveness of a benchmarking initiative in facilitating
      quality improvement and reform in extended care mental health services. METHOD:
      Individual interviews and focus group discussions were conducted with 84 staff in
      22 extended care mental health services that had previously participated in a
      State-wide benchmarking exercise in Queensland, Australia. RESULTS: Staff
      reported positive outcomes from participation in the benchmarking exercise.
      Information derived from benchmarking provided a different perspective on the
      strengths and weaknesses of individual services and an opportunity to learn from
      peer services. Staff in 86% of the services identified issues that needed to be
      addressed and 64% of services had implemented one or more service improvement
      projects in response to shortcomings identified through the benchmarking
      exercise. CONCLUSIONS: The collection and reporting of performance data through a
      process of benchmarking was successful in facilitating service improvement in
      most of the participating facilities. Engaging services in all stages of the
      process was considered useful in converting benchmarking data into knowledge that
      was able to be applied at the local service level.

PMID- 20797367
TI  - Evaluation of the impact of implementation of a Medical Assessment and Planning
      Unit on length of stay.
AB  - OBJECTIVE: The Medical Assessment and Planning Unit (MAPU) model provides a
      multidisciplinary and 'front end loading' approach to acute medical care. The
      objective of this study was to evaluate the impact of a 10-bed MAPU in Royal
      Melbourne Hospital (RMH) on hospital length of stay. METHODS: A pre-post study
      design was used. Cases were defined as all general medical patients admitted to
      the RMH between 1 August 2003 and 31 January 2004. MAPU patients were defined as
      general medical patients who had been discharged from RMH MAPU unit as part of
      their RMH inpatient admission. Historical controls were defined as all general
      medical patients admitted to the RMH between 1 August 2002 and 31 January 2003.
      RESULTS: There was a reduction in median length of stay that did not reach
      statistical significance. During the study period, median emergency department
      length of stay for MAPU patients was 10.3 h compared with 13.2 h for non-MAPU
      patients who were admitted directly to general wards. CONCLUSIONS: The reductions
      in length of stay are likely to be of clinical significance at the emergency
      department (ED) level. The MAPU model also contributes to providing care
      appropriate care for older admitted patients.

PMID- 20797368
TI  - From leader to leadership: clinician managers and where to next?
AB  - Individual clinician leadership is at the forefront of health reforms in
      Australia as well as overseas with many programs run by health departments (and
      hospitals) generally focus on the development of individual leaders. This paper
      argues, along with others, that leadership in the clinician management context
      cannot be understood from an individualistic approach alone. Clinician managers,
      especially in the ranks of doctors, are usually described as 'hybrid-professional
      managers' as well as reluctant leaders for whom most leadership theories do not
      easily apply. Their experiences of leadership development programs run by health
      departments both in Australia and internationally are likely to be based on an
      individual leader-focussed approach that is driving health care reforms. These
      approaches work from three key assumptions: (1) study and fix the person; (2)
      give them a position or title; and (3) make them responsible for results. Some
      would argue that the combination of these three approaches equates to heroic and
      transformational leadership. Several alternative approaches to leadership
      development are presented to illustrate how reforms in healthcare, and notably in
      hospitals, must incorporate alternative approaches, such as those based on
      collective and relational forms of leadership. This does not mean eschewing
      individual approaches to leadership but rather, thinking of them differently and
      making them more relevant to the daily experiences of clinician managers. We
      conclude by highlighting several significant challenges facing leadership
      development for clinician managers that arise from these considerations.

PMID- 20797369
TI  - The Clinical Services Redesign Program in New South Wales: perceptions of senior
      health managers.
AB  - OBJECTIVE: This study explores the views of senior managers regarding their
      experience of participating in the Clinical Services Redesign Program (CSRP) in
      New South Wales and the impact of that Program. METHODS: Semi-structured
      interviews were conducted in 2007 with 42 senior managers working in the NSW
      health system. RESULTS: Managers reported being increasingly oriented towards
      efficiency, achieving results and using data to support decision-making. The
      increased focus on managing performance was accompanied by concerns about the
      narrowness of the indicators being used to manage performance and how these are
      applied. The value placed by interviewees on the use of 'competition' as a lever
      for improving services varied. Leadership was repeatedly identified as important
      for long-term success and sustainability. No one was confident that the CSRP had
      yet been sufficiently embedded in day to day practice in order for it to keep
      going on its own. CONCLUSION: Our findings are generally consistent with the
      extensive literature on change management, performance management and leadership.
      Some cultural change has taken place in terms of observed patterns of behaviour
      but it is unrealistic to think that CSRP can on its own deliver the desired
      deeper cultural changes in the values and assumptions underpinning the NSW Health
      system. There is some evidence of dysfunctional aspects of performance management
      but no call for the focus on performance or redesign to be abandoned.

PMID- 20797370
TI  - Empowerment and change management in Aboriginal organisations: a case study.
AB  - The social organisation of work, management styles and social relationships in
      the workplace all matter for health. It is now well recognised that people who
      have control over their work have better health and that stress in the workplace
      increases the level of disease. In the context of organisational change, the
      potential benefits of empowerment strategies are two-fold: a positive impact on
      the organisation's effectiveness and enhancements in staff health, wellbeing and
      sense of control. This case study describes the University of Queensland
      Empowerment Research Program's experience working with the Apunipima Cape York
      Health Council in a change management process. Participatory action research and
      empowerment strategies were utilised to facilitate shifts in work culture and
      group cohesion towards achieving Apunipima's vision of being an effective lead
      agency for Indigenous health reform in Cape York. As part of the project, staff
      morale and confidence were monitored using a pictorial tool, Change Curve, which
      outlined the phases of organisational change. The project findings indicated that
      organisational change did not follow a clear linear trajectory. In some ways the
      dynamics mapped over a period of 18 months mirror the type of struggles
      individuals commonly encounter as a part of personal growth and development. In
      this case, one of the factors which influenced the program's success was the
      willingness of executive employees to actively support and participate in the
      change management process.

PMID- 20797371
TI  - Implications of excess weight on mental wellbeing.
AB  - OBJECTIVE: To assess differences in perceived health-related quality of life
      among individuals who are normal weight, overweight and obese in the general
      population, with particular emphasis on mental health. METHOD: A cross-sectional
      study was conducted among the general adult population in Queensland, Australia.
      Participants (n = 1212) were selected randomly for computer-assisted telephone
      interview in July 2007. The sample ranged between 18 and 93 years, with a mean
      age of 51.10 years (s.d. = 15.92). Demographic and physical and mental health (SF
      12) data were collected. Self-reported height and weight were used to classify
      participants into three groups based on their body mass index: normal weight;
      overweight; obese. The associations between body mass index categories and SF-12
      scores were investigated. RESULTS: In this population sample, excess weight was
      associated with poorer physical health. In addition, significant associations
      were observed between excess weight and poor mental health for particular age
      groups. Obesity had a significant association with poor mental wellbeing for
      individuals who are aged 45 to 54 years. No sex differences were observed.
      CONCLUSION: The results provide additional evidence of the relationship between
      excess weight and mental wellbeing and highlight the need for health
      professionals to be cognisant of the potential for individuals who are obese to
      have a higher risk of experiencing mental health problems.

PMID- 20797372
TI  - Do doctors, nurses and managers have different thinking styles?
AB  - A study of the preferred thinking styles among senior health professionals is
      reported. A total of 49 medical consultants, 50 senior nurses and 53 health
      managers from two public teaching hospitals in Adelaide, Australia, were invited
      via a personal letter to complete a questionnaire comprising measures of thinking
      style (the Rational Experiential Inventory) and cognitive style (two dimensions
      of the Myers-Briggs Type Indicator). Managers reported a higher preference for
      'rational' reasoning than nurses, whereas medical consultants reported a lower
      preference for 'experiential' reasoning than both managers and nurses. Cognitive
      style was largely homogenous. Although generalisation of the findings may be
      limited due to small sample sizes and the self-selection of participants, an
      understanding of the thinking styles of senior health professionals will likely
      inform the design and evaluation of future change strategies.

PMID- 20797374
TI  - Monitoring adults with ADHD: a focus on executive and behavioral function.
AB  - Deficits in executive function have been consistently demonstrated in adults with
      ADHD. Rating scales that measure executive deficits in relation to daily life are
      useful in assessing ADHD symptoms and in measuring responses to treatment, while
      neuropsychological testing can measure deficits in executive function that can
      cause additional impairment in adults with ADHD. Treatments, including
      psychosocial interventions and stimulant and nonstimulant medications, can be
      helpful in addressing these executive deficits and the symptoms of adult ADHD.

PMID- 20797373
TI  - Suicidality and risk of suicide--definition, drug safety concerns, and a
      necessary target for drug development: a consensus statement.
AB  - OBJECTIVE: To address issues concerning potential treatment-emergent
      "suicidality," a consensus conference was convened March 23-24, 2009.
      PARTICIPANTS: This gathering of participants from academia, government, and
      industry brought together experts in suicide prevention, clinical trial design,
      psychometrics, pharmacoepidemiology, and genetics, as well as research
      psychiatrists involved in studies of major depression, bipolar disorder,
      schizophrenia, substance abuse/dependence, and other psychiatric disorders
      associated with elevated suicide risk across the life cycle. The process involved
      reviews of the relevant literature, and a series of 6 breakout sessions focused
      on specific questions of interest. EVIDENCE: Each of the participants at the
      meeting received references relevant to the formal presentations (as well as the
      slides for the presentations) for their review prior to the meeting. In addition,
      the assessment instruments of suicidal ideation/behavior were reviewed in
      relationship to standard measures of validity, reliability, and clinical utility,
      and these findings were discussed at length in relevant breakout groups, in the
      final plenary session, and in the preparation of the article. Consensus and
      dissenting views were noted. CONSENSUS PROCESS: Discussion and questions followed
      each formal presentation during the plenary sessions. Approximately 6 questions
      per breakout group were prepared in advance by members of the Steering Committee
      and each breakout group chair. Consensus in the breakout groups was achieved by
      nominal group process. Consensus recommendations and any dissent were reviewed
      for each breakout group at the final plenary session. All plenary sessions were
      recorded and transcribed by a court stenographer. Following the transcript, with
      input by each of the authors, the final paper went through 14 drafts. The output
      of the meeting was organized into this scholarly article, which has been
      developed by the authors with feedback from all participants at the meeting and
      represents a consensus view. Any areas of disagreement have been noted.
      CONCLUSIONS: The term suicidality is not as clinically useful as more specific
      terminology (ideation, behavior, attempts, and suicide). Most participants
      applauded the FDA's effort to promote standard definitions and definable
      expectations for investigators and industry sponsors by endorsing the terminology
      in the Columbia Classification Algorithm of Suicide Assessment (C-CASA). Further
      research of available assessment instruments is needed to verify their utility,
      reliability, and validity in identifying suicide-associated treatment-emergent
      adverse effects and/or a signal of efficacy in suicide prevention trials. The FDA
      needs to build upon its new authority to systematically monitor postmarketing
      events by encouraging the development of a validated instrument for postmarketing
      surveillance of suicidal ideation, behavior, and risk within informative large
      health care-related databases in the United States and abroad. Over time, the
      FDA, industry, and clinical researchers should evaluate the impact of the current
      Agency requirement that all CNS clinical drug trials must include a C-CASA
      compatible screening instrument for assessing and documenting the occurrence of
      treatment-emergent suicidal ideation and behavior. Finally, patients at high risk
      for suicide can safely be included in clinical trials, if proper precautions are
      followed, and they need to be included to enable premarket assessments of the
      risks and benefits of medications related to suicidal ideation, suicidal
      behavior, and suicide in such patients.

PMID- 20797375
TI  - Performance improvement CME: improving outcomes in depression.
AB  - Performance Improvement CME (PI CME) is an educational activity in which
      clinicians retrospectively assess their current clinical practice, choose areas
      for improvement and implement interventions based on treatment guidelines and
      health care standards, and then re-evaluate their clinical practice to assess the
      improvements made. This PI CME focuses on improving the detection and initial
      treatment of depression, enhancing patients' treatment response, and preventing
      relapse and recurrence.

PMID- 20797376
TI  - Nonpharmacologic care of patients with fibromyalgia.
AB  - A key long-term goal for patients with fibromyalgia is for them to become experts
      in understanding their own symptoms and treatment responses to further successful
      self-management of their condition. Patient education about fibromyalgia is key,
      as are several nonpharmacologic strategies such as encouraging the patient to
      have a realistic, positive attitude and outlook; engage in a regular, paced
      program of physical activity and exercise; and adopt positive sleep hygiene
      practices. To meet their goals, patients with fibromyalgia will need support and
      understanding from the clinician and other treatment team members.

PMID- 20797377
TI  - The future of psychopharmacology of depression.
AB  - There are clear limitations to the currently approved pharmacotherapies of
      depression, including the fact that they are all essentially monoamine-based,
      have modest efficacy and a relatively slow onset of efficacy, and suffer from
      significant tolerability issues, particularly in the long term, including sexual
      dysfunction, weight gain, and cognitive impairments. This article reviews some of
      the most promising novel mechanisms that are not represented in compounds
      currently approved for depression in either the United States or Europe and that
      may represent the future of the psychopharmacologic treatment of depression,
      potentially addressing some of the efficacy and tolerability issues of
      antidepressants on the market. These potential antidepressant treatments include
      the multimodal serotonergic agents, the triple uptake inhibitors, the neurokinin
      based novel therapies, the glutamatergic treatments, the nicotinic receptor-based
      treatments, the neurogenesis-based treatments, and antiglucocorticoid therapies.
      Some of these mechanisms appear to be more advanced in terms of drug development
      than others, but they all contribute to the global effort to develop more
      effective and better tolerated treatments for major depressive disorder.

PMID- 20797378
TI  - Clozapine: more side effects but still the best antipsychotic.

PMID- 20797379
TI  - Prediction of recurrence in recurrent depression: a 5.5-year prospective study.
AB  - OBJECTIVE: Depression is a disease with high recurrence rates. Identifying
      predictors of recurrence and their relative importance in patients with recurrent
      depression is important for a better understanding of the course of this disease.
      This type of knowledge can be used to optimize and tailor preventive strategies
      of recurrence. In this study, we examined predictors of recurrence over a 5.5
      year follow-up period and quantified to which extent these predictors explained
      observed variation in recurrence. METHOD: Data from 172 remitted recurrently
      depressed patients over a 5.5-year follow-up period were used. Recurrence was
      assessed with the Structured Clinical Interview for DSM-IV. Illness-, stress-,
      and coping-related factors were examined as predictors of recurrence. Multiple
      Cox regression analysis was used, and explained variation was assessed to
      quantify the relative importance of the predictors. Patients were recruited
      between February 2000 and September 2000. RESULTS: Number of previous episodes
      and residual symptoms explained each 15% of the variation in recurrence,
      indicating a medium effect size. The final multivariate prediction model
      included: a higher number of previous episodes, more residual symptoms, and lower
      levels of positive refocusing (explained variation 29%, indicating a strong
      effect size). CONCLUSION: In our multivariate prediction model, the number of
      previous episodes, residual symptoms, and a specific coping style were predictors
      of recurrence over a 5.5-year follow-up period in remitted recurrently depressed
      patients. Preventive therapies should focus on these factors. Although a
      substantial part of variation in recurrence (29%) was explained by these
      predictors, most of it remains unexplained. Consequently, recurrence remains a
      difficult to predict and only partially understood phenomenon. TRIAL
      REGISTRATION: International Standard Randomized Controlled Trial Register
      Identifier: ISRCTN68246470.

PMID- 20797380
TI  - Karolinska Interpersonal Violence Scale predicts suicide in suicide attempters.
AB  - BACKGROUND: Both childhood trauma and violent behavior are important risk factors
      for suicidal behavior. The aim of the present study was to construct and validate
      a clinical rating scale that could measure both the exposure to and the
      expression of violence in childhood and during adult life and to study the
      ability of the Karolinska Interpersonal Violence Scale (KIVS) to predict ultimate
      suicide in suicide attempters. METHOD: A total of 161 suicide attempters and 95
      healthy volunteers were assessed with the KIVS measuring exposure to violence and
      expressed violent behavior in childhood (between 6-14 years of age) and during
      adult life (15 years or older). The Buss-Durkee Hostility Inventory (BDHI), "Urge
      to act out hostility" subscale from the Hostility and Direction of Hostility
      Questionnaire (HDHQ), and the Early Experience Questionnaire (EEQ) were used for
      validation. All patients were followed up for cause of death and a minimum of 4
      years from entering in the study. RESULTS: Five patients who committed suicide
      within 4 years had significantly higher scores in exposure to violence as a
      child, in expressed violent behavior as an adult, and in KIVS total score
      compared to survivors. Suicide attempters scored significantly higher compared to
      healthy volunteers in 3 of the 4 KIVS subscales. There were significant
      correlations between the subscales measuring exposure to and expression of
      violent behavior during the life cycle. BDHI, Urge to act out hostility, and EEQ
      validated the KIVS. CONCLUSIONS: Exposure to violence in childhood and violent
      behavior in adulthood are risk factors for completed suicide in suicide
      attempters. Behavioral dysregulation of aggression is important to assess in
      clinical work. The KIVS is a valuable new tool for case detection and long-term
      clinical suicide prevention.

PMID- 20797381
TI  - A 2-year prospective follow-up study of the course of obsessive-compulsive
      disorder.
AB  - BACKGROUND: Surprisingly little is known about the long-term course of obsessive
      compulsive disorder (OCD). This prospective study presents 2-year course
      findings, as well as predictors of course, from the Brown Longitudinal Obsessive
      Compulsive Study, the first comprehensive prospective investigation of the
      observational course of OCD in a large clinical sample. METHOD: The sample
      included 214 treatment-seeking adults with DSM-IV OCD at intake who identified
      OCD as the most problematic disorder over their lifetime. Subjects were enrolled
      from 2001-2004. At annual interviews, data on weekly OCD symptom status were
      obtained using the Longitudinal Interval Follow-Up Evaluation. Probabilities of
      full remission and partial remission over the first 2 years of collected data and
      potential predictors of remission were examined. RESULTS: The probability of full
      remission from OCD was 0.06, and the probability of partial remission was 0.24.
      Of the 48 subjects whose OCD symptoms partially or fully remitted, only 1
      relapsed within the first 2 years. Earlier age at onset of OCD, greater severity
      of symptoms at intake, older age at intake, and being male were associated with a
      decreased likelihood of remission. Insight, diagnostic comorbidity, and treatment
      were not found to be associated with the likelihood of achieving full or partial
      remission. CONCLUSIONS: Though one-quarter of the sample had periods of
      subclinical OCD symptoms during the prospective period, full remission was rare,
      consistent with the view of OCD as a chronic and persistent illness. Age at
      onset, OCD symptom severity, current age, and sex emerged as potent predictors of
      course.

PMID- 20797382
TI  - Short-term efficacy and safety of desvenlafaxine in a randomized, placebo
      controlled study of perimenopausal and postmenopausal women with major depressive
      disorder.
AB  - BACKGROUND: The risk for major depressive disorder (MDD) increases during the
      menopausal transition. Nonetheless, no large, placebo-controlled studies have
      prospectively assessed the efficacy of antidepressants in perimenopausal or
      postmenopausal women. This randomized, double-blind, placebo-controlled trial
      evaluated the short-term efficacy and safety of desvenlafaxine (administered as
      desvenlafaxine succinate) in perimenopausal and postmenopausal women with DSM-IV
      defined MDD. METHOD: 387 depressed perimenopausal and postmenopausal women aged
      40 to 70 years were randomly assigned to placebo or desvenlafaxine (100 or 200
      mg/d at the discretion of the investigator) in an 8-week, flexible-dose trial
      conducted from September 2006 to June 2008. The primary efficacy variable was
      change from baseline in 17-item Hamilton Depression Rating Scale (HDRS(17)) total
      score, analyzed using a mixed-effects model for repeated-measures analysis.
      Safety data were collected throughout the trial. RESULTS: The reduction in
      adjusted HDRS17 total scores from baseline to week 8 (mean daily dose after
      titration, 162 to 176 mg/d) was significantly greater for desvenlafaxine (-12.64)
      compared with placebo (-8.33; P < .001). Statistical separation from placebo was
      observed at week 1 and was sustained through week 8. Both the perimenopausal and
      postmenopausal subgroups achieved significant reductions in HDRS(17) total scores
      with desvenlafaxine treatment (perimenopausal, P = .003; postmenopausal, P <
      .001). Response (58.6%) and remission (38.2%) rates were significantly higher for
      desvenlafaxine compared with placebo (31.6% [P < .001] and 22.4% [P = .008],
      respectively). In all, 19/256 (7.4%) desvenlafaxine-treated patients and 4/125
      (3.2%) placebo-treated patients discontinued due to adverse events. Treatment
      emergent adverse events were reported by 94/125 (75.2%) placebo-treated patients
      and 218/256 (85.2%) desvenlafaxine-treated patients. CONCLUSIONS: Short-term
      treatment with desvenlafaxine was effective and generally well tolerated in
      perimenopausal and postmenopausal women with MDD. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00369343.

PMID- 20797383
TI  - Bereavement, complicated grief, and DSM, part 2: complicated grief.

PMID- 20797384
TI  - Posttraumatic stress disorder and health-related quality of life in pension
      seeking Canadian World War II and Korean War veterans.

PMID- 20797385
TI  - REM sleep behavior disorder in psychiatric populations.

PMID- 20797386
TI  - Characterisation of the purified human sodium/iodide symporter reveals that the
      protein is mainly present in a dimeric form and permits the detailed study of a
      native C-terminal fragment.
AB  - The sodium/iodide symporter is an intrinsic membrane protein that actively
      transports iodide into thyroid follicular cells. It is a key element in thyroid
      hormone biosynthesis and in the radiotherapy of thyroid tumours and their
      metastases. Sodium/iodide symporter is a very hydrophobic protein that belongs to
      the family of sodium/solute symporters. As for many other membrane proteins,
      particularly mammalian ones, little is known about its biochemistry and
      structure. It is predicted to contain 13 transmembrane helices, with an N
      terminus oriented extracellularly. The C-terminal, cytosolic domain contains
      approximately one hundred amino acid residues and bears most of the transporter's
      putative regulatory sites (phosphorylation, sumoylation, di-acide, di-leucine or
      PDZ-binding motifs). In this study, we report the establishment of eukaryotic
      cell lines stably expressing various human sodium/iodide symporter recombinant
      proteins, and the development of a purification protocol which allowed us to
      purify milligram quantities of the human transporter. The quaternary structure of
      membrane transporters is considered to be essential for their function and
      regulation. Here, the oligomeric state of human sodium/iodide symporter was
      analysed for the first time using purified protein, by size exclusion
      chromatography and light scattering spectroscopy, revealing that the protein
      exists mainly as a dimer which is stabilised by a disulfide bridge. In addition,
      the existence of a sodium/iodide symporter C-terminal fragment interacting with
      the protein was also highlighted. We have shown that this fragment exists in
      various species and cell types, and demonstrated that it contains the amino-acids
      [512-643] from the human sodium/iodide symporter protein and, therefore, the last
      predicted transmembrane helix. Expression of either the [1-512] truncated domain
      or the [512-643] domain alone, as well as co-expression of the two fragments, was
      performed, and revealed that co-expression of [1-512] with [512-643] allowed the
      reconstitution of a functional protein. These findings constitute an important
      step towards an understanding of some of the post-translational mechanisms that
      finely tune iodide accumulation through human sodium/iodide symporter regulation.

PMID- 20797387
TI  - JS-K, a nitric oxide-releasing prodrug, modulates beta-catenin/TCF signaling in
      leukemic Jurkat cells: evidence of an S-nitrosylated mechanism.
AB  - beta-Catenin is a central player of the Wnt signaling pathway that regulates cell
      cell adhesion and may promote leukemia cell proliferation. We examined whether JS
      K, an NO-donating prodrug, modulates the Wnt/beta-catenin/TCF-4 signaling pathway
      in Jurkat T-Acute Lymphoblastic Leukemia cells. JS-K inhibited Jurkat T cell
      growth in a concentration and time-dependent manner. The IC(50)s for cell growth
      inhibition were 14+/-0.7 and 9+/-1.2MUM at 24 and 48h, respectively. Treatment of
      the cells with JS-K for 24h, caused a dose-dependent increase in apoptosis from
      16+/-3.3% at 10MUM to 74.8+/-2% at 100MUM and a decrease in proliferation. This
      growth inhibition was also due, in part, to alterations in the different phases
      of the cell cycle. JS-K exhibited a dose-dependent cytotoxicity as measured by
      LDH release at 24h. However, between 2 and 8h, LDH release was less than 20% for
      any indicated JS-K concentration. The beta-catenin/TCF-4 transcriptional
      inhibitory activity was reduced by 32+/-8, 63+/-5, and 93+/-2% at 2, 10, and
      25MUM JS-K, respectively, based on luciferase reporter assays. JS-K reduced
      nuclear beta-catenin and cyclin D1 protein levels, but cytosolic beta-catenin
      expression did not change. Based on a time-course assay of S-nitrosylation of
      proteins by a biotin switch assay, S-nitrsolyation of nuclear beta-catenin was
      determined to precede its degradation. A comparison of the S-nitrosylated nuclear
      beta-catenin to the total nuclear beta-catenin showed that beta-catenin protein
      levels were degraded at 24h, while S-nitrosylation of beta-catenin occurred
      earlier at 0-6h. The NO scavenger PTIO abrogated the JS-K mediated degradation of
      beta-catenin demonstrating the need for NO.

PMID- 20797388
TI  - Influence of the flavonoids apigenin, kaempferol, and quercetin on the function
      of organic anion transporting polypeptides 1A2 and 2B1.
AB  - OATP1A2 and OATP2B1 are uptake transporters of the human organic anion
      transporting polypeptide (OATP) family with a broad substrate spectrum including
      several endogenous compounds as well as drugs such as the antihistaminic drug
      fexofenadine and HMG-CoA reductase inhibitors. Both transporters are localized in
      the apical membrane of human enterocytes. Flavonoids, abundantly occurring in
      plants, have previously been shown to interact with drug metabolizing enzymes and
      transporters. However, the impact of flavonoids on OATP1A2 and OATP2B1 transport
      function has not been analyzed in detail. Therefore, HEK293 cell lines stably
      expressing OATP1A2 and OATP2B1 were used to investigate the influence of the
      Ginkgo flavonoids apigenin, kaempferol, and quercetin on the transport activity
      of OATP1A2 and OATP2B1. K(i) values of all three flavonoids determined from Dixon
      plot analyses using BSP as substrate indicated a competitive inhibition with
      quercetin as the most potent inhibitor of OATP1A2 (22.0MUM) and OATP2B1 (8.7MUM)
      followed by kaempferol (OATP1A2: 25.2MUM, OATP2B1: 15.1MUM) and apigenin
      (OATP1A2: 32.4MUM OATP2B1: 20.8MUM). Apigenin, kaempferol, and quercetin led to a
      concentration-dependent decrease of the OATP1A2-mediated fexofenadine transport
      with IC(50) values of 4.3MUM, 12.0MUM, and 12.6MUM, respectively. The OATP1A2-
      and OATP2B1-mediated transport of atorvastatin was also efficiently inhibited by
      apigenin (IC(50) for OATP1A2: 9.3MUM, OATP2B1: 13.9MUM), kaempferol (IC(50) for
      OATP1A2: 37.3MUM, OATP2B1: 20.7MUM) and quercetin (IC(50) for OATP1A2: 13.5MUM,
      OATP2B1: 14.1MUM). These data indicate that modification of OATP1A2 and OATP2B1
      transport activity by apigenin, kaempferol, and quercetin may be a mechanism for
      food-drug or drug-drug interactions in humans.

PMID- 20797389
TI  - AMPK agonist downregulates innate and adaptive immune responses in TNBS-induced
      murine acute and relapsing colitis.
AB  - AMP-activated protein kinase (AMPK), a cellular energy sensor, has been reported
      to participate in modulating inflammatory responses, but its role in intestinal
      inflammation remains unclear. IBD has been characterized by excessive innate and
      adaptive immune responses. Here, the roles of 5-aminoimidazole-4-carboxamide
      ribonucleoside (AICAR), an agonist of AMPK, in regulating immune responses of
      experimental colitis were investigated. In vitro effects of AICAR on LPS-induced
      macrophage activation and Th1 and Th17 differentiation, as well as in vivo
      effects of AICAR in mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced
      colitis, were explored. In acute colitis, daily AICAR treatment commenced 2 days
      after TNBS delivery (day 1), while in relapsing colitis, AICAR treatment
      commenced after three weekly TNBS administrations. Colon inflammation, production
      of proinflammatory cytokines and NF-kappaB activation in colon tissues, and Th1
      and Th17 cell populations in lamina propria mononuclear cells (LPMCs) and
      mesenteric lymph node cells (MLNs) were assayed. Results show that AICAR
      significantly inhibited in vitro LPS-induced macrophage activation and Th1 and
      Th17 cell differentiation. Administration of AICAR was therapeutically effective
      in ameliorating acute and relapsing experimental colitis, as shown by reduced
      body weight loss and significant attenuation in colon histological inflammation.
      Moreover, this treatment inhibited NF-kappaB activation in macrophages, and
      reduced levels of TNF, Th1- and Th17-type cytokines, and Th1 and Th17 cell
      populations in LPMCs and MLNs. AICAR-initiated AMPK activation may act as a
      central downregulator in ongoing innate and adaptive immune responses of murine
      colitis, providing a novel therapeutic approach in the treatment of IBD.

PMID- 20797390
TI  - Direct fusion of subunits of heterodimeric nitric oxide sensitive guanylyl
      cyclase leads to functional enzymes with preserved biochemical properties:
      evidence for isoform specific activation by ciguates.
AB  - Nitric oxide sensitive guanylyl cyclase (NOsGC) is a heterodimeric enzyme
      consisting of an alpha and a beta subunit. Two heterodimeric enzymes are known to
      be important for NO-signalling in humans: alpha(1)/beta(1) and alpha(2)/beta(1).
      No difference had so far been detected with respect to their pharmacological
      properties, but as we show in the present paper the new drugs cinaciguat and
      ataciguat activate the alpha(1)/beta(1) form more effectively. Recent evidence
      suggests that homodimeric complexes of alpha and beta subunits exist in vivo and
      that these non-heterodimerizing subunits have a separate function from cGMP
      signaling. To isolate the effect of the alpha(1)/beta(1) or alpha(2)/beta(1)
      heterodimeric enzyme in overexpression experiments from potential effects of non
      heterodimerizing alpha(1), beta(1) or alpha(2) subunits, we cloned constructs
      that guarantee a 1:1 stochiometry between alpha and beta subunits and rule out
      the presence of homodimers. The carboxy-terminus of the beta(1) subunit was
      directly fused to the amino-terminus of either the alpha(1) or alpha(2) subunit.
      The two different "conjoined" NOsGCs faithfully reproduced the biochemical and
      pharmacological properties of the alpha(1)/beta(1) and alpha(2)/beta(1)
      heterodimeric enzymes including the differential activation by ciguat-activators.
      Conjoined NOsGCs can be used for isoform specific overexpression in transgenic
      animals and therapeutic overexpression may be an application in the future. In
      both cases possible side effects of homodimeric alpha or beta subunits are
      avoided. Crystallization with the goal of structure determination may also be
      easier for conjoined NOsGCs because enzyme preparations are more homogenous and
      are free of "contaminating" homodimers.

PMID- 20797391
TI  - Interruption of visually perceived forward motion in depth evokes a cortical
      activation shift from spatial to intentional motor regions.
AB  - Forward locomotion generates a radially expanding flow of visual motion which
      supports goal-directed walking. In stationary mode, wide-field visual
      presentation of optic flow stimuli evokes the illusion of forward self-motion.
      These effects illustrate an intimate relation between visual and motor
      processing. In the present fMRI study, we applied optic flow to identify distinct
      interfaces between circuitries implicated in vision and movement. The dorsal
      premotor cortex (PMd) was expected to contribute to wide-field forward motion
      flow (FFw), reflecting a pathway for externally triggered motor control. Medial
      prefrontal activation was expected to follow interrupted optic flow urging
      internally generated action. Data of 15 healthy subjects were analyzed with
      Statistical Parametric Mapping and confirmed this hypothesis. Right PMd
      activation was seen in FFw, together with activations of posterior parietal
      cortex, ventral V5, and the right fusiform gyrus. Conjunction analysis of the
      transition from wide to narrow forward flow and reversed wide-field flow revealed
      selective dorsal medial prefrontal activation. These findings point at equivalent
      visuomotor transformations in locomotion and goal-directed hand movement, in
      which parietal-premotor circuitry is crucially implicated. Possible implications
      of an activation shift from spatial to intentional motor regions for
      understanding freezing of gait in Parkinson's disease are discussed: impaired
      medial prefrontal function in Parkinson's disease may reflect an insufficient
      internal motor drive when visual support from optic flow is reduced at the
      entrance of a narrow corridor.

PMID- 20797392
TI  - Renal tubular cell membranes inhibit growth but promote aggregation of calcium
      oxalate monohydrate crystals.
AB  - Cell membranes have been proposed to serve as promoters for calcium oxalate
      monohydrate (COM) kidney stone formation. However, direct evidence to demonstrate
      the modulatory effects of renal tubular cell membranes on COM crystals does not
      currently exist. We thus examined the effects of intact MDCK cells and their
      fragmented membranes on COM crystal growth, aggregation and transformation. COM
      crystals were generated in the absence (control) or presence of intact MDCK cells
      or their membrane fragments. Intact MDCK cells and their membrane fragments
      significantly inhibited COM crystal growth (22.6% and 25.2% decreases in size,
      respectively) and significantly reduced COM total crystal mass (23.1% and 25.6%
      decreases, respectively). In contrast, both of them markedly promoted crystal
      aggregation (1.9-fold and 3.2-fold increases, respectively). Moreover, both
      intact cells and membrane fragments could transform COM to calcium oxalate
      dihydrate (COD) crystals. Finally, COM crystal growth inhibitory activities of
      both membrane forms were successfully confirmed by a spectrophotometric oxalate
      depletion assay. Our data provide the first direct evidence to demonstrate the
      dual modulatory effects of MDCK membranes on COM crystals. Although growth of
      individual COM crystals was inhibited, their aggregation was promoted. These
      findings provide additional insights into the mechanisms of COM kidney stone
      formation.

PMID- 20797393
TI  - Tauroursodeoxycholate counteracts hepatocellular lysis induced by tensioactive
      bile salts by preventing plasma membrane-micelle transition.
AB  - Ursodeoxycholic acid is widely used as a therapeutic agent for the treatment of
      cholestatic liver diseases. In these hepatopathies, the bile secretory failure
      produces accumulation of endogenous, tensioactive bile salts, leading to plasma
      membrane damage and, eventually, hepatocellular lysis. In the present study, we
      analyzed the capacity of the ursodeoxycholic acid endogenous metabolite,
      tauroursodeoxycholate (TUDC), to stabilize the hepatocellular plasma membrane
      against its transition to the micellar phase induced by the tensioactive bile
      salt taurochenodeoxycholate (TCDC), the main endogenous bile salt accumulated in
      cholestasis. The disruption of the plasma membrane was evaluated (i) in isolated
      hepatocytes, through the release of the enzyme lactate dehydrogenase to the
      incubation medium and (ii) in isolated plasma membranes, through the self
      quenching assay of the membranotropic probe octadecylrhodamine B; this assay
      allows for detergent-induced transition from membrane bilayer to micelle to be
      monitored. Our results showed that isolated hepatocytes treated with TUDC are
      more resistant to TCDC-induced cell lysis. When this effect was evaluated in
      isolated plasma membranes, the TCDC concentration necessary to reach half of the
      transition from bilayer to micelle was increased by 22% (p<0.05). This difference
      remained even when TUDC was removed from the incubation medium before adding
      TCDC, thus indicating that TUDC exerted its effect directly on the plasma
      membrane. When the same experiments were carried out using the non-ionic
      detergent TX-100 or the cholesterol-complexing detergent digitonin, no protective
      effect was observed. In conclusion, TUDC prevents selectively the bilayer to
      micelle transition of the hepatocellular plasma membrane induced by hydrophobic
      bile salts that typically build up and accumulate in cholestatic processes. Our
      results suggest that formation of a complex between negatively charged TUDC and
      cholesterol in the membrane favours repulsion of negatively charged detergent
      bile salts, thus providing a basis for the understanding of the TUDC protective
      effects.

PMID- 20797394
TI  - Genetic variants of human urea transporter-2 are associated with metabolic
      syndrome in Asian population.
AB  - BACKGROUND: A previous study has reported that the Ile227 and Ala357 genetic
      variants of human urea transporter-2 (HUT2) were associated with blood pressure
      in males in Asian population. In this study, we aimed to investigate five known
      HUT2 genetic variants with metabolic syndrome (MetS) and its related traits in
      the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance
      (SAPPHIRe) study cohort. METHODS: Five HUT2 single nucleotide polymorphisms
      (SNPs) were selected and genotyped among 1791 subjects in the SAPPHIRe study
      cohort. We first computed allele frequency and performed Hardy-Weinberg
      equilibrium (HWE) test in controls for each SNP. Next, we tested genotype
      associations with metabolic syndrome using multiple generalized estimating
      equations (GEE) models with covariate adjustment. Furthermore, multi-marker and
      multi-trait association tests were carried out using FBAT program. To account for
      multiple testing, Bonferroni correction was applied in this study. RESULTS: Among
      those 5 HUT2 SNPs, SNPs 1, 2 and 3 were significantly associated with MetS in the
      total sample and females, separately (9*10(-4)<=p<=0.04), but only the
      association between SNP 1 and MetS in females remained statistically significant
      after Bonferroni correction. When testing 5 SNPs simultaneously, significant
      associations were found with triglycerides (TG) (p=0.04). Likewise, significant
      multi-trait association (combining the data of waist circumference, TG, high
      density lipoprotein (HDL) cholesterol and fasting glucose together) was found
      with SNP 2 (p=0.04), but both results of multi-maker and multi-trait associations
      did not remain significant after multiple testing correction. CONCLUSION: The
      results have provided evidence that the HUT2 gene may play a certain role in
      developing MetS and its related traits in Asian population. Further investigation
      of the HUT2 gene influencing MetS and its related traits will be warranted.

PMID- 20797395
TI  - Evaluation of a Schiff base copper complex compound as potent anticancer molecule
      with multiple targets of action.
AB  - Copper is a biologically relevant metal as it is associated with various
      biomolecules related to essential physiological activities. Anticancer compounds
      with copper as a metal center is hypothesized to be less toxic and more potent.
      In the present study we have tested the efficacy of a family of Schiff base
      copper complexes of which the best compound was [Cu(Pyimpy)Cl(2)] where Pyimpy is
      a tridentate ligand containing two pyridine and one imine nitrogen donor.
      [Cu(Pyimpy)Cl(2)], represented as CuP1, was checked for its anticancer potential.
      The IC(50) value of CuP1 was found to be 4.29+/-0.42, 6.34+/-0.58 and 5.32+/-0.38
      MUM in MCF-7, PC3 and HEK 293 cells respectively. It was found to cause in vitro
      DNA fragmentation in comet assays and acridine orange staining of MCF 7 cells.
      CuP1 was further tested on rat breast tumor models and was found to inhibit tumor
      growth. It caused apoptosis within the tumor by the up regulation of caspase
      pathway and inhibition of the Akt, matrix metalloproteinase 9 and alpha-methyl
      acyl CoA racemase. Antioxidant enzymes which in general results in drug resistant
      condition in tumor tissues were significantly inhibited by this copper compound
      (P<0.05). Further, CuP1 did not show any prominent systemic toxicity. These
      results indicate that CuP1 can be a potential anticancer agent and further
      investigation will reveal more about its mode of action.

PMID- 20797396
TI  - Expression of TREM-1 is inhibited by PGD2 and PGJ2 in macrophages.
AB  - TREM-1 is a superimmunoglobulin receptor present on neutrophils and monocytes,
      which plays an important role in the amplification of inflammation. The natural
      ligands for TREM-1 have not been identified; however, Toll-like receptor ligands
      are known to induce the expression of TREM-1. Blockade of TREM-1 has shown to
      improve survival in animal models of sepsis. In the present studies, we
      investigated the role of lipid mediators in the expression of TREM-1. In a
      macrophage cell line, we show that the expression of TREM-1 in response to LPS
      and bacteria Pseudomonas aeruginosa is inhibited by PGD(2) and cyclopentanone
      prostaglandins PGJ(2) and 15-dPGJ(2). The inhibition of TREM-1 by these
      prostaglandins is independent of the PGD(2) receptors and PPARgamma but occurs by
      activation of Nrf2 and inhibition of NF-kappaB. Our data suggest a novel
      mechanism by which these prostaglandins exhibit anti-inflammatory effects and a
      new therapeutic approach to inhibition of TREM-1.

PMID- 20797397
TI  - Processing-independent analysis for pro-C-type natriuretic peptide.
AB  - C-type natriuretic peptide (CNP) is expressed in several human tissues. We
      designed a specific processing-independent assay for proCNP-derived products and
      quantitated the concentrations in human seminal plasma from normal and
      vasectomized men. Antibodies were raised against the N-terminus of human proCNP
      11-27. Samples were incubated with trypsin prior to immunoassay, which allows for
      the measurement of "total" proCNP irrespective of the degree of post
      translational processing. Seminal plasma from normal young men and vasectomized
      men were collected and quantitated; the molecular heterogeneity was evaluated by
      gel chromatography. The antiserum displayed high binding affinity. Preanalytical
      trypsin treatment fully exposed the proCNP 11-27 epitope detected by the
      antiserum. Seminal plasma from healthy men (n=120) contained ~8-fold higher
      proCNP concentrations compared to blood plasma (range 104-933 pmol/L, age 18-25
      years); gel chromatography suggested the presence of several molecular forms.
      Parameters associated to male fertility, proCNP concentrations in blood plasma
      and time of abstinence did not correlate to the seminal proCNP concentrations.
      Measurement in vasectomized men disclosed seminal proCNP concentrations similar
      to non-vasectomized men (range 107-705 pmol/L, age 34-44 years). Taken together,
      our new proCNP assay shows that proCNP is abundantly present in human seminal
      plasma and that seminal proCNP is secreted from the prostate gland and/or the
      seminal vesicles.

PMID- 20797398
TI  - Evidence that the acute phase of ischemic preconditioning does not require
      signaling by the A 2B adenosine receptor.
AB  - Ischemic preconditioning (IPC) is a protective phenomenon in which brief ischemia
      renders the myocardium resistant to subsequent ischemic insults. Here, we used
      A(2B)AR gene knock-out (A(2B)KO)/beta-galactosidase reporter gene knock-in mice
      and the A(2B)AR antagonist ATL-801 to investigate the potential involvement of
      the A(2B)AR in IPC, focusing on the acute phase of protection. Cardioprotection
      provided by acute IPC elicited by two 3-min occlusion/3-min reperfusion cycles
      was readily apparent in an isolated, Langendorff-perfused mouse heart model in
      studies using hearts from A(2B)KO mice. IPC equivalently improved the recovery of
      contractile function following 20 min of global ischemia and 45 min of
      reperfusion in both WT and A(2B)KO hearts by ~30-40%, and equivalently decreased
      the release of cardiac troponin I during the reperfusion period (from 5969 +/-
      925 to 1595 +/- 674 ng/g and 4376 +/- 739 to 2278 +/- 462 ng/g using WT and
      A(2B)KO hearts, respectively). Similarly, the infarct size-reducing capacity of
      acute IPC in an in vivo model of infarction was fully manifested in experiments
      using A(2B)KO mice, as well as in experiments using rats pretreated with ATL-801.
      We did observe, however, a marked reduction in infarct size in rats following
      administration of the selective A(2B)AR agonist BAY 60-6583 (~25% reduction at a
      dose of 1.0mg/kg). While supportive of its concept as a cardioprotective
      receptor, these experiments indicate that the mechanism of the early phase of IPC
      is not dependent on signaling by the A(2B)AR. We present the idea that the
      A(2B)AR may contribute to the later stages of IPC dependent on the induction of
      stress-responsive genes.

PMID- 20797399
TI  - Limitations of FKBP12.6-directed treatment strategies for maladaptive cardiac
      remodeling and heart failure.
AB  - Sarcoplasmic reticulum (SR) calcium (Ca) leak can be reduced by enhancing
      FKBP12.6 binding to SR Ca release channels (RyR2) and expression of a "sticky"
      FKBP12.6(D37S) mutant may correct reduced binding stoichiometry in RyR2 from
      failing hearts. Both calcium/calmodulin-dependent protein kinase IIdeltac
      (CaMKIIdeltac) and protein kinase A (PKA) are activated in heart failure and
      promote SR Ca leak at RyR2. It is possible that FKBP12.6 dissociation from RyR2
      may promote remodeling and that interventions to reassociate FKBP12.6 with RyR2
      reflect a future therapeutic strategy. We created transgenic (TG) mice expressing
      FKBP12.6(D37S) and tested their capacity to improve intracellular Ca handling and
      pathological remodeling in vivo. FKBP12.6(D37S) TG mice were cross-bred with
      CaMKIIdeltac TG mice, which are known to exhibit pronounced RyR2 dysfunction and
      heart failure. We observed a significant improvement of post-rest Ca transients
      and a higher SR Ca content in FKBP12.6(D37S) TG mice. In double-TG mice, a marked
      reduction of SR Ca spark frequency indicated reduced SR Ca leak but neither SR Ca
      transient amplitude, SR Ca content nor morphological or functional parameters
      improved in vivo. Likewise, FKBP12.6(D37S) TG mice subjected to increased
      afterload after aortic banding exhibited higher SR Ca load but did not exhibit
      any improvement in hypertrophic growth or functional decline. Enhancement of
      FKBP12.6-RyR2 binding markedly reduced RyR2 Ca leak in CaMKIIdeltac-induced heart
      failure and in pressure overload. Our data suggest that activation of
      CaMKIIdeltac and pressure overload confer significant resistance towards
      approaches aiming at FKBP12.6-RyR2 reconstitution in heart failure and
      maladaptive remodeling, although RyR2 Ca leak can be reduced.

PMID- 20797400
TI  - Conserved hydrophobic clusters on the surface of the Caf1A usher C-terminal
      domain are important for F1 antigen assembly.
AB  - The outer membrane usher protein Caf1A of the plague pathogen Yersinia pestis is
      responsible for the assembly of a major surface antigen, the F1 capsule. The F1
      capsule is mainly formed by thin linear polymers of Caf1 (capsular antigen
      fraction 1) protein subunits. The Caf1A usher promotes polymerization of subunits
      and secretion of growing polymers to the cell surface. The usher monomer (811 aa,
      90.5 kDa) consists of a large transmembrane beta-barrel that forms a secretion
      channel and three soluble domains. The periplasmic N-terminal domain binds
      chaperone-subunit complexes supplying new subunits for the growing fiber. The
      middle domain, which is structurally similar to Caf1 and other fimbrial subunits,
      serves as a plug that regulates the permeability of the usher. Here we describe
      the identification, characterization, and crystal structure of the Caf1A usher C
      terminal domain (Caf1A(C)). Caf1A(C) is shown to be a periplasmic domain with a
      seven-stranded beta-barrel fold. Analysis of C-terminal truncation mutants of
      Caf1A demonstrated that the presence of Caf1A(C) is crucial for the function of
      the usher in vivo, but that it is not required for the initial binding of
      chaperone-subunit complexes to the usher. Two clusters of conserved hydrophobic
      residues on the surface of Caf1A(C) were found to be essential for the efficient
      assembly of surface polymers. These clusters are conserved between the FGL family
      and the FGS family of chaperone-usher systems.

PMID- 20797401
TI  - Equivalent activation of the hippocampus by face-face and face-laugh paired
      associate learning and recognition.
AB  - The human hippocampus is known to play an important role in relational memory.
      Both patient lesion studies and functional-imaging studies have shown that it is
      involved in the encoding and retrieval from memory of arbitrary associations. Two
      recent patient lesion studies, however, have found dissociations between spared
      and impaired memory within the domain of relational memory. Recognition of
      associations between information of the same kind (e.g., two faces) was spared,
      whereas recognition of associations between information of different kinds (e.g.,
      face-name or face-voice associations) was impaired by hippocampal lesions. Thus,
      recognition of associations between information of the same kind may not be
      mediated by the hippocampus. Few imaging studies have directly compared
      activation at encoding and recognition of associations between same and different
      types of information. Those that have have shown mixed findings and been open to
      alternative interpretation. We used fMRI to compare hippocampal activation while
      participants studied and later recognized face-face and face-laugh paired
      associates. We found no differences in hippocampal activation between our two
      types of stimulus materials during either study or recognition. Study of both
      types of paired associate activated the hippocampus bilaterally, but the
      hippocampus was not activated by either condition during recognition. Our
      findings suggest that the human hippocampus is normally engaged to a similar
      extent by study and recognition of associations between information of the same
      kind and associations between information of different kinds.

PMID- 20797402
TI  - New palytoxin-like molecules in Mediterranean Ostreopsis cf. ovata
      (dinoflagellates) and in Palythoa tuberculosa detected by liquid chromatography
      electrospray ionization time-of-flight mass spectrometry.
AB  - A rapid, high resolution liquid chromatography coupled with ElectroSpray
      Ionization Time-Of-Flight Mass Spectrometry (ESI/TOF/MS) method was developed for
      the determination of the toxin pattern in cultured cells of Ostreopsis cf. ovata
      from the Mediterranean Sea. The samples were separated on a Phenomenex Luna 3MU
      HILIC 200A (150 * 2.00 mm) and analyzed by LC/TOF/MS with electrospray ionization
      (ESI) interface in positive ion mode. The method developed here provides the
      capability for a fully automated analysis, which requires relatively easy sample
      preparation and gives clean and simple chromatograms. The method was successfully
      applied to the determination of ovatoxin-a, mascarenotoxin-a and four new
      palytoxins in O. cf. ovata. Another new palytoxin was detected in the standard
      material from Palythoa tuberculosa provided by Wako Chemicals.

PMID- 20797403
TI  - The impacts of organochlorines and other persistent pollutants on thyroid and
      metabolic health.
AB  - High prevalence of thyroid and metabolic disorders has been repeatedly observed
      in the population living in the area of eastern Slovakia highly polluted by a
      mixture of PCBs, DDE and HCB since about 50 years ago. Among thyroid disorders,
      increase of thyroid volume as measured by ultrasound volumetry may be suggested
      as one of notable findings which appeared possibly related to increased OCs
      levels and to autoimmunity signs (e.g. positive thyroperoxidase antibodies in
      blood and/or hypoechogenicity image obtained by ultrasound), while some
      participation of individual susceptibility and also of immunogenic effect of OCs
      and iodine in this iodine replete country cannot be excluded. Another notable
      finding has been the increase of blood FT4 and TT3 positively related to high
      PCBs level. Such increased FT4 level has been found associated with TSH level in
      hyperthyroid range in about 2% of examined population from polluted area. High
      prevalence of thyroid autoimmune disorders strongly supported the assumption on
      impaired immune system and thus also on presumably increased prevalence of other
      autoimmune disorders in highly exposed population. In addition, markedly
      increased prevalence of prediabetes and diabetes significantly related to major
      OCs (PCBs, DDE and HCB) levels and accompanied by increasing level of cholesterol
      and triglycerides has been observed. The observations also suggested a role of
      prenatal exposure to OCs in the development of several adverse health signs (e.g.
      increased prevalence of thyroid antibodies, impaired fasting glucose level,
      increased thyroid volume, decreased thymus volume, decreased neurobehavioral
      performance, increased hearing and dental disorders) in young generation born to
      highly exposed mothers in polluted area.

PMID- 20797404
TI  - Alginate-based ferrofluid and magnetic microsphere thereof.
AB  - The Fe(3)O(4) ferrofluids have been prepared using sodium alginate (Na-AL) as a
      stabilizing agent. The alginate can prevent the aggregation of magnetic
      nanoparticles and hence contributed to higher stability for the ferrofluids.
      Furthermore, the alginate component in the ferrofluids was crosslinked by Ca(2+)
      to produce magnetic microspheres. The swelling behavior of magnetic microspheres
      showed a pH-dependence, and hence determined the drug release process under
      various pH conditions. The presence of the Fe(3)O(4) nanoparticles made the
      magnetic microspheres swell more easily. Meanwhile, the strong ability to absorb
      the drug for the incorporated Fe(3)O(4) nanoparticles decreased the release rate
      and hence was more favorable to the sustaining release of drug. Except for the
      controlled delivery and release of drug, the alginate-based ferrofluids and
      magnetic microspheres in this work might also show a great potential for other
      biomedical and biotechnological applications, such as, magnetic targeting,
      magnetic separation and magnetic resonance imaging.

PMID- 20797405
TI  - Chronic low-level Pb exposure during development decreases the expression of the
      voltage-dependent anion channel in auditory neurons of the brainstem.
AB  - Lead (Pb) exposure is a risk factor for neurological dysfunction. How Pb produces
      these behavioral deficits is unknown, but Pb exposure during development is
      associated with auditory temporal processing deficits in both humans and animals.
      Pb disrupts cellular energy metabolism and efficient energy production is crucial
      for auditory neurons to maintain high rates of synaptic activity. The voltage
      dependent anion channel (VDAC) is involved in the regulation of mitochondrial
      physiology and is a critical component in controlling mitochondrial energy
      production. We have previously demonstrated that VDAC is an in vitro target for
      Pb, therefore, VDAC may represent a potential target for Pb in the auditory
      system. In order to determine whether Pb alters VDAC expression in central
      auditory neurons, CBA/CaJ mice (n=3-5/group) were exposed to 0.01mM, or 0.1mM Pb
      acetate during development via drinking water. At P21, immunohistochemistry
      reveals a significant decrease for VDAC in neurons of the Medial Nucleus of the
      Trapezoid Body. Western blot analysis confirms that Pb results in a significant
      decrease for VDAC. Decreases in VDAC expression could lead to an upregulation of
      other cellular energy producing systems as a compensatory mechanism, and a Pb
      induced increase in brain type creatine kinase is observed in auditory regions of
      the brainstem. In addition, comparative proteomic analysis shows that several
      proteins of the glycolytic pathway, the phosphocreatine circuit, and oxidative
      phosphorylation are also upregulated in response to developmental Pb exposure.
      Thus, Pb-induced decreases in VDAC could have a significant effect on the
      function of auditory neurons.

PMID- 20797406
TI  - Functional status determined by Barthel Index predicts community acquired
      pneumonia mortality in general population.
AB  - BACKGROUND: Barthel Index (BI) measures functional status. Our aim was to analyze
      if BI and other factors not included in Pneumonia Severity Index (PSI) predict
      mortality in general population with community acquired pneumonia (CAP). METHODS:
      Prospective observational study including all patients with CAP diagnosed in
      2006. Endpoint of study: 30-day mortality. Variables not included in PSI as BI
      were analyzed. Strength of association was determined by odds ratio (OR) with 95%
      confidence interval. RESULTS: 550 patients, mean age of 60.3 +/- 20.8, were
      included. 32 were lost during follow-up and 518 patients were finally analyzed.
      44 (8.5%) patients died in the first 30 days after CAP diagnosis. In bivariate
      analysis, mortality was significantly more frequent in patients with PSI >= IV
      (19.2% vs 1.9%), BI<=80 points (23.9% vs 2.9%), multilobar infiltrate (20% vs
      6%), diabetes mellitus (14.9% vs 6.5%), influenza vaccination (11.9% vs 6.6%) and
      pneumococcal vaccination (16.7% vs 6%). In multivariate analysis, mortality
      independently associated factors were: BI <=80, OR: 3.9(CI95% 1.4-10.5; p <
      0.001); PSI >= IV OR: 3.9(1.2-12.7; p < 0.05); and multilobar infiltrate OR:
      2.9(1.1-7.3; p = 0.05). CONCLUSION: A BI score <=80 is associated with a higher
      mortality in patients with CAP independently of the PSI. BI can be a useful tool
      to predict CAP mortality in general population.

PMID- 20797407
TI  - Intravenous micafungin versus voriconazole for chronic pulmonary aspergillosis: a
      multicenter trial in Japan.
AB  - Chronic pulmonary aspergillosis (CPA) is slowly progressive inflammatory
      pulmonary syndrome due to Aspergillus spp. The evidence regarding CPA treatment
      is limited. We conducted a randomized, multicenter, open-label trial comparing
      intravenous micafungin (MCFG) of 150-300 mg once daily with intravenous
      voriconazole (VRCZ) of 6 mg/kg twice on Day 1 followed by 4 mg/kg twice daily for
      the treatment of 107 in patients with CPA to compare the efficacy and safety of
      both drugs as initial treatment in Japan. Treatment effectiveness was defined by
      clinical, mycological, radiological and serological responses 2 weeks after the
      initial administration and at the end of therapy. The total of 50 and 47 patients
      were assigned to the MCFG and VRCZ groups, respectively. The difference in
      efficacy rates between MCFG and VRCZ was not significant, either after 2 weeks
      [68.0% vs. 58.7%; the absolute difference, 9.3% with a 95% confidence interval
      (CI), -9.97 to 28.58, P = 0.344] or at the end of therapy (60.0% vs. 53.2%; the
      absolute difference, 6.8% with a 95% CI, -12.92 to 26.54, P = 0.499). In the
      safety evaluation, fewer adverse events occurred in the MCFG than VRCZ group
      (26.4% vs. 61.1%, P = 0.0004). MCFG was as effective as VRCZ and significantly
      safer than as an initial treatment of CPA. (UMIN Clinical Trials Registry number,
      UMIN000001786.).

PMID- 20797408
TI  - Isolation of a human anti-epidermal growth factor receptor Fab antibody, EG-19
      11, with subnanomolar affinity from naive immunoglobulin repertoires using a
      hierarchical antibody library system.
AB  - Specific antibodies that possess a subnanomolar affinity are very difficult to
      obtain from human naive immunoglobulin repertoires without the use of lengthy
      affinity optimization procedures. Here, we designed a hierarchical phage
      displayed antibody library system to generate an enormous diversity of
      combinatorial Fab fragments (6*10(17)) and attempted to isolate high-affinity
      Fabs against the human epidermal growth factor receptor (EGFR). A primary
      antibody library, designated HuDVFab-8L, comprising 4.5*10(9) human naive heavy
      chains and eight unspecified human naive light chains was selected against the
      EGFR-Fc protein by biopanning, and four anti-EGFR Fab clones were isolated.
      Because one of the Fab clones, denoted EG-L2-11, recognized a native EGFR
      expressed on A431 cells, the heavy chain of the Fab was shuffled with a human
      naive light chain repertoire with a diversity of 1.4*10(8) and selected a second
      time against the EGFR-Fc protein again. One EG-L2-11 variant, denoted EG-19-11,
      recognized an EGFR epitope that was almost the same as that bound by cetuximab
      and had a K(D) of approximately 540 pM for soluble EGFR, which is about 7-fold
      higher than that of the FabC225 derived from cetuximab. This variant was also
      internalized by A431 cells, likely via receptor-mediated endocytosis, and it
      efficiently inhibited EGF-mediated tyrosine phosphorylation of the EGFR. These
      results demonstrate that the use of our hierarchical antibody library system is
      advantageous in generating fully human antibodies especially with a therapeutic
      purpose.

PMID- 20797409
TI  - Local hyperthermia could induce antiviral activity by endogenous interferon
      dependent pathway in condyloma acuminata.
AB  - Local hyperthermia has been successfully used in the treatment of viral warts by
      mechanisms that have largely remained unclear. Using an organotypic culture
      system, we found that hyperthermia at 42  degrees C and 45  degrees C could
      induce a significant increase in the transcriptional expression of interferon
      (IFN)-alpha, IFN-beta and IFN-gamma, in a temperature-dependent manner in
      condyloma acuminata (CA), but not in normal skin. Accordingly, local hyperthermia
      could enhance the expression of 2'-5' oligoadenylate synthase and double-stranded
      RNA (dsRNA)-dependent protein kinase, two antiviral enzymes downstream of the IFN
      dependant pathway. Hyperthermia led to an increase in IFN-alpha/beta receptor
      transcripts, and an increase in the levels in phospho-Stat1 and phospho-Stat2 in
      CA, though it had no influence on the levels of Jak1, Tyk2, Stat1 and Stat2
      transcriptional expression. Local hyperthermia was proved effective in treating
      human papillomavirus-infected skin. These results suggested that hyperthermia
      took effect partly by inducing the expression of local endogenous IFN and partly
      by subsequent IFN-induced antiviral activity via Jak-STATs signalling pathway in
      CA.

PMID- 20797410
TI  - A neurotoxic regimen of methamphetamine impairs novelty recognition as measured
      by a social odor-based task.
AB  - Repeated administration of methamphetamine (mAMPH) to rodents in a single-day
      "binge" regimen damages forebrain monoaminergic nerve terminals and produces
      subsequent cognitive deficits. Here we investigate performance on a social odor
      based task, demonstrating enduring mAMPH-induced deficits in recognition memory.
      Three weeks after a neurotoxic mAMPH regimen, singly-housed male Long-Evans rats
      had four wooden beads placed in their home cage: three beads containing odors
      from their home cage (HC beads) and one bead from a cage of a rat not present in
      the colony room (N1 bead). Exploration times for each bead were recorded during
      three 1-min habituation trials separated by 1-min intertrial intervals. Twenty
      four hours later, a 1-min memory test was conducted, in which animals were
      presented with two HC beads, one N1 bead, and one bead from another novel animal
      (N2). Saline- and mAMPH-treated rats showed similar, progressive decreases in
      exploration time for the N1 bead during the habituation trials, indicating
      equivalent short-term olfactory habituation to the novel odor. By contrast,
      during the subsequent memory test, saline-treated rats showed a strong preference
      for the N2 bead over the N1 bead while mAMPH-treated rats showed no preference.
      The use of the rats' primary sensory modality (olfaction) coupled with the social
      significance (from conspecifics) of the odors produces strong, long-lasting
      memories. Our results show that prior treatment with a neurotoxic regimen of
      mAMPH impairs long-term memory for the previously experienced odors. As compared
      with previously employed object recognition tasks, this test may be advantageous
      for investigating mAMPH-induced memory impairments in rodents.

PMID- 20797411
TI  - Effect of caloric and non-caloric sweet reward solutions on thermal facial
      operant conditioning.
AB  - Sweet solutions are commonly used in animal research to deliver drugs to test for
      addictive capacity and efficacy. In this study we compared the effects of a range
      of sucrose and saccharin concentrations on the performance of an operant assay.
      Our findings demonstrate that across a range of sucrose solutions some produce a
      success ratio which could mistakenly be labeled allodynic demonstrating the
      importance of choosing the correct reward solution.

PMID- 20797412
TI  - Electrophysiological correlates of inter- and intrahemispheric saccade-related
      updating of visual space.
AB  - The process of spatial updating is crucial for maintaining perceptual stability
      despite gross and frequent displacements of space following saccadic eye
      movements. Efference copies of motor commands are used to update retinal
      coordinates across saccades. The present study investigated neural correlates of
      saccadic updating in a perceptual context with regard to temporal dynamics and
      modulation by intra- versus interhemispheric transfer of updating-related
      information. Twenty-two subjects engaged in a perceptual localization task which
      required trans-saccadic spatial updating while event-related potentials (ERPs)
      were recorded. In accordance with previous studies, post-saccadic perceptual
      localization of stimuli presented before a saccade was less accurate when relying
      on efference copy signals (i.e. updating was required) as compared to a control
      condition not involving updating. Updating-related ERP components emerged before
      and after saccade onset. There was no clear transfer-dependent modulation of the
      presaccadic component. A negative deflection between 30 and 70 ms after saccade
      onset was most pronounced for rightward saccades, and when intrahemispheric
      transfer was required. A slower positive deflection starting about 170-230 ms
      after saccade onset had a shorter latency for leftward than for rightward
      saccades and was not modulated by transfer. In accordance with previous work,
      this relative positivity is thought to reflect sensory memory, whereas the
      earlier negative deflection can be more directly linked to the updating process
      itself.

PMID- 20797413
TI  - Depth-of-processing effects on memory encoding after selective
      amygdalohippocampectomy.
AB  - Deeper semantic processing improves memory encoding of words. Neuroimaging
      studies suggest, that left-hemispheric structures, especially the left inferior
      frontal cortex and the left hippocampus mediate this effect. Therefore, we
      tested, whether chronic left hippocampal damage in epilepsy patients after
      selective amygdalohippocampectomy (SAH) diminishes the depth-of-processing effect
      in an incidental learning task. 16 patients after left SAH, 17 after right SAH
      and 15 healthy control subjects elaborated on word classification tasks under a
      non-semantic and two different semantic conditions. Recognition memory for the
      words was subsequently tested. Although memory in left SAH patients profited less
      from deeper semantic processing in terms of an absolute increase in the number of
      recognized words, the relative level of memory impairment compared to the two
      other groups was identical under the non-semantic and the semantic conditions.
      The results indicate that chronic left hippocampal damage affects recognition
      memory largely independent of semantic processing.

PMID- 20797414
TI  - Deep and shallow encoding effects on face recognition: an ERP study.
AB  - Event related potentials (ERPs) were employed to investigate whether and when
      brain activity related to face recognition varies according to the processing
      level undertaken at encoding. Recognition was assessed when preceded by a
      "shallow" (orientation judgement) or by a "deep" study task (occupation
      judgement). Moreover, we included a further manipulation by presenting at
      encoding faces either in the upright or inverted orientation. As expected, deeply
      encoded faces were recognized more accurately and more quickly with respect to
      shallowly encoded faces. The ERP showed three main findings: i) as witnessed by
      more positive-going potentials for deeply encoded faces, at early and later
      processing stage, face recognition was influenced by the processing strategy
      adopted during encoding; ii) structural encoding, indexed by the N170, turned out
      to be "cognitively penetrable" showing repetition priming effects for deeply
      encoded faces; iii) face inversion, by disrupting configural processing during
      encoding, influenced memory related processes for deeply encoded faces and
      impaired the recognition of faces shallowly processed. The present study adds
      weight to the concept that the depth of processing during memory encoding affects
      retrieval. We found that successful retrieval following deep encoding involved
      both familiarity- and recollection-related processes showing from 500 ms a fronto
      parietal distribution, whereas shallow encoding affected only earlier processing
      stages reflecting perceptual priming.

PMID- 20797415
TI  - Microbial production of virus-like particle vaccine protein at gram-per-litre
      levels.
AB  - This study demonstrates the feasibility of large-scale production of murine
      polyomavirus VP1 protein in recombinant Escherichia coli as pentamers which are
      able to subsequently self-assemble in vitro into virus-like particles (VLPs).
      High-cell-density pH-stat fed-batch cultivation was employed to produce
      glutathione-S-transferase (GST)-VP1 fusion protein in soluble form. The
      expression of recombinant VP1 was induced with IPTG at different cell optical
      densities (OD at 600 nm of 20, 60 or 100). GST-VP1 production was highest when
      the culture was induced at a cell density of OD 60, with volumetric yield
      reaching 4.38 gL-1 in 31h, which we believe is the highest volumetric
      productivity for viral capsid protein reported to date. The induction cell
      density is shown to have a significant effect on the overall volumetric yield of
      recombinant VP1 and on final cell density, but not on VLP quality. VP1 yield was
      enhanced 15-fold by scaling-up from shake flask to pH-stat fed-batch cultivation
      in a bioreactor. Although numerous studies have expressed structural viral
      protein in E. coli, we believe this is the first report of translation to
      bioreactors yielding gram-per-litre levels. This VLP production technology
      overcomes major drawbacks associated with eukaryotic cell-based vaccine
      production technologies, and propounds the scope for large-scale commercially
      viable E. coli based VLP production by significantly reducing vaccine production
      time and cost.

PMID- 20797416
TI  - Amino acid uptake profiling of wild type and recombinant Streptomyces lividans
      TK24 batch fermentations.
AB  - Streptomyces lividans is considered an interesting host for the secretory
      production of heterologous proteins. To obtain a good secretion yield of
      heterologous proteins, the availability of suitable nitrogen sources in the
      medium is required. Often, undefined mixtures of amino acids are used to improve
      protein yields. However, the understanding of amino acid utilization as well as
      their contribution to the heterologous protein synthesis is poor. In this paper,
      amino acid utilization by wild type and recombinant S. lividans TK24 growing on a
      minimal medium supplemented with casamino acids is profiled by intensive analysis
      of the exometabolome (metabolic footprint) as a function of time. Dynamics of
      biomass, substrates, by-products and heterologous protein are characterized,
      analyzed and compared. As an exemplary protein mouse Tumor Necrosis Factor Alpha
      (mTNF-alpha) is considered. Results unveil preferential glutamate and aspartate
      assimilation, together with glucose and ammonium, but the associated high biomass
      growth rate is unfavorable for protein production. Excretion of organic acids as
      well as alanine is observed. Pyruvate and alanine overflow point at an imbalance
      between carbon and nitrogen catabolism and biosynthetic fluxes. Lactate secretion
      is probably related to clump formation. Heterologous protein production induces a
      slowdown in growth, denser clump formation and a shift in metabolism, as
      reflected in the altered substrate requirements and overflow pattern. Besides
      glutamate and aspartate, most amino acids are catabolized, however, their exact
      contribution in heterologous protein production could not be seized from
      macroscopic quantities. The metabolic footprints presented in this paper provide
      a first insight into the impact and relevance of amino acids on biomass growth
      and protein production. Type and availability of substrates together with biomass
      growth rate and morphology affect the protein secretion efficiency and should be
      optimally controlled, e.g., by appropriate medium formulation and substrate
      dosing. Overflow metabolism as well as high biomass growth rates must be avoided
      because they reduce protein yields. Further investigation of the intracellular
      metabolic fluxes should be conducted to fully unravel and identify ways to
      relieve the metabolic burden of plasmid maintenance and heterologous protein
      production and to prevent overflow.

PMID- 20797417
TI  - Investigation of a unique short open reading frame within the 3' untranslated
      region of the canine distemper virus matrix messenger RNA.
AB  - Increasing evidence suggest that the long "untranslated" region (UTR) between the
      matrix (M) and the fusion (F) proteins of morbilliviruses has a functional role.
      In canine distemper virus (CDV), the F 5' UTR was recently shown to code for a
      long F signal peptide (Fsp). Subsequently, it was reported that the M/F UTRs
      combined with the long Fsp were synergistically regulating the F mRNA and protein
      expression, thereby modulating virulence. Unique to CDV, a short putative open
      reading frame (ORF) has been identified within the wild-type CDV-M 3' UTR (termed
      M2). Here, we investigated whether M2 was expressed from the genome of the
      virulent and demyelinating A75/17-CDV strain. An expression plasmid encoding the
      M2 ORF tagged both at its N-terminal (HA) and C-terminal domains (RFP), was first
      constructed. Then, a recombinant virus with its putative M2 ORF replaced by HA-M2
      RFP was successfully recovered from cDNA (termed recA75/17(green)-HA-M2-RFP). M2
      expression in cells transfected or infected with these mutants was studied by
      immunoprecipitation, immunofluorescence, immunoblot and flow cytometry analyses.
      Although fluorescence was readily detected in HA-M2-RFP-transfected cells,
      absence of red fluorescence emission in several recA75/17(green)-HA-M2-RFP
      infected cell types suggested lack of M2 biosynthesis, which was confirmed by the
      other techniques. Consistent with these data, no functional role of the short
      polypeptide was revealed by infecting various cell types with HA-M2-RFP over
      expressing or M2-knockout recombinant viruses. Thus, in sharp contrast to the CDV
      F 5' UTR reported to translate a long Fsp, our data provided evidence that the
      CDV-M 3' UTR does not express any polypeptides.

PMID- 20797418
TI  - Paclitaxel-loaded Pluronic nanoparticles formed by a temperature-induced phase
      transition for cancer therapy.
AB  - We prepared nanoparticles by a temperature-induced phase transition in a mixture
      of Pluronic F-68 and liquid PEG (polyethylene glycol, molecular weight: 400)
      containing paclitaxel (PTX) with a fast, simple, continuous and solvent-free
      process. The liquid PEG is used as solubilizer of PTX and the polymer for the
      encapsulation of PTX is composed of Pluronic F-68. At the phase transition
      temperature, the polymer mixture was changed to the liquid phase, and stirring
      the liquid 0  degrees C to form Pluronic nanoparticles. The morphology and size
      distribution of the prepared Pluronic nanoparticles were observed using FE-SEM
      and TEM, and a particle size analyzer and cryo-TEM were used to observe the shape
      of paclitaxel-loaded Pluronic nanoparticles in an aqueous state. To apply
      Pluronic nanoparticles as a delivery system for cancer therapy, the release
      pattern of PTX, a model anti-cancer drug, was observed and the tumor growth was
      monitored by injecting the PTX-loaded Pluronic nanoparticles into the tail veins
      of tumor-bearing mice. We also evaluated the time-dependent excretion profile, in
      vivo biodistribution, circulation time, and tumor targeting ability of PTX-loaded
      Pluronic nanoparticles using non-invasive live animal imaging technology. In the
      early stage within 7h of release, the loaded PTX was rapidly released and the
      sustained release was observed for up to 48 h. In vivo studies, PTX-loaded
      Pluronic nanoparticles were observed with higher anti-tumor efficacy compared
      with PTX formulated in Cremophor EL.

PMID- 20797419
TI  - To exploit the tumor microenvironment: Passive and active tumor targeting of
      nanocarriers for anti-cancer drug delivery.
AB  - Because of the particular characteristics of the tumor microenvironment and tumor
      angiogenesis, it is possible to design drug delivery systems that specifically
      target anti-cancer drugs to tumors. Most of the conventional chemotherapeutic
      agents have poor pharmacokinetics profiles and are distributed non-specifically
      in the body leading to systemic toxicity associated with serious side effects.
      Therefore, the development of drug delivery systems able to target the tumor site
      is becoming a real challenge that is currently addressed. Nanomedicine can reach
      tumor passively through the leaky vasculature surrounding the tumors by the
      Enhanced Permeability and Retention effect whereas ligands grafted at the surface
      of nanocarriers allow active targeting by binding to the receptors overexpressed
      by cancer cells or angiogenic endothelial cells. This review is divided into two
      parts: the first one describes the tumor microenvironment and the second one
      focuses on the exploitation and the understanding of these characteristics to
      design new drug delivery systems targeting the tumor. Delivery of conventional
      chemotherapeutic anti-cancer drugs is mainly discussed.

PMID- 20797421
TI  - Carotenoids as regulators for inter-species difference in cytochrome P450 1A
      expression and activity in ungulates and rats.
AB  - Ungulates (deer, cattle and horses) are reported as animal species which show
      extreme-accelerated metabolism of CYP1A substrates, such as ethoxyresorufin
      compared to rats. This study was undertaken to investigate whether accumulation
      of carotenoids is a possible cause for inter-species difference in CYP1A
      dependent activity in this group of animals. The relationship between inter
      species differences in CYP1A-dependent activity and the accumulated carotenoids
      and retinoids as candidates of dietary CYP1A inducers in ungulate species was
      clarified. Interestingly, there were positive correlations between the
      accumulated carotenoids, such as beta-carotene, with both EROD activity and CYP1A
      protein expression. These correlations were negative with the accumulated
      retinoids, such as retinol. The beta-carotene was major component of carotenoids
      in ungulates, and known as an inducer of CYP1A. On the other hand, the retinol is
      reported as the inhibitor of CYP1A. Other factors which affect CYP1A1 expression,
      such as polycyclic aromatic hydrocarbons, were also analyzed. To cancel the
      effects of inter-species difference in CYP1A induction signal cascade among these
      animals, the rat cell line (H4-II-cells) was treated with the extracted
      carotenoids from the examined animals. In conclusion, carotenoids and retinoids
      may have direct effects on the inter-species differences in CYP1A-dependent
      activity and protein expression.

PMID- 20797420
TI  - Human RFamide-related peptide-1 diminishes cellular and integrated cardiac
      contractile performance.
AB  - Peptides influence cardiac dysfunction; however, peptidergic modulation of
      contractile performance remains relatively uncharacterized. We identified a novel
      human peptide that modulates mammalian contractile performance. Members of the
      FMRFamide-related peptide (FaRP) family contain a C-terminal RFamide but
      structurally variant N-terminal extension. We report human RFamide-related
      peptide-1 (hRFRP-1) and rat RFRP-1 rapidly and reversibly decreased shortening
      and relaxation in isolated mammalian cardiac myocytes in a dose dependent manner.
      The mammalian FaRP, 26RFa, structurally related to RFRP-1 by only an RFamide did
      not influence myocyte contractile function. The protein kinase C (PKC) inhibitor
      bisindolylmaleimide-1 blocked hRFRP-1 activity. Pretreatment with pertussis toxin
      (PTX) did not diminish hRFRP-1 influence on contractile function. In addition,
      intravenous injection of hRFRP-1 in mice decreased heart rate, stroke volume,
      ejection fraction, and cardiac output. Collectively these findings are consistent
      with the conclusion RFRP-1 is an endogenous signaling molecule that activates PKC
      and acts through a PTX-insensitive pathway to modulate cardiac contractile
      function. Taken together these negative chronotropic, inotropic, and lusitropic
      effects of hRFRP-1 are significant; they suggest direct acute cellular and organ
      level responses in mammalian heart. This is the first known study to identify a
      mammalian FaRP with cardio-depressant effects, opening a new area of research on
      peptidergic modulation of contractile performance. The high degree of RFRP
      structure conservation from amphibians to mammals, and similarity to invertebrate
      cardioinhibitory peptides suggests RFRP-1 is involved in important physiological
      functions. Elucidation of mechanisms involved in hRFRP-1 synthesis, release, and
      signaling may aid the development of strategies to prevent or attenuate cardiac
      dysfunction.

PMID- 20797422
TI  - Isolation and characterization of the cDNA encoding DH(31) in the kissing bug,
      Rhodnius prolixus.
AB  - Rhodnius prolixus undergoes a period of rapid diuresis after ingesting large
      blood meals. Neurohormones with either diuretic or anti-diuretic activity control
      diuresis by acting on several tissues including the Malpighian tubules. One of
      the neurohormones that potentially plays a role in diuresis is diuretic hormone
      31 (DH(31)) which belongs to the insect calcitonin-like family of diuretic
      hormones. Here we determine the complete cDNA sequences of three Rhopr-DH(31)
      splice variants (Rhopr-DH(31)-A, Rhopr-DH(31)-B and Rhopr-DH(31)-C) and
      characterize their expression in unfed fifth-instar R. prolixus. Reverse
      transcriptase-PCR demonstrates that Rhopr-DH(31) is predominantly expressed in
      the central nervous system (CNS) of unfed fifth-instars. However, the expression
      of the three splice variants differs with Rhopr-DH(31)-B expression being the
      highest followed by Rhopr-DH(31)-A and Rhopr-DH(31)-C, as determined using semi
      quantitative Southern blot analysis. Fluorescent in situ hybridization reveals
      that Rhopr-DH(31) is expressed in a variety of cells in the CNS, including some
      neurosecretory cells.

PMID- 20797424
TI  - Co-expression of somatostatin receptor subtypes and estrogen receptor-alpha mRNAs
      by non-functioning pituitary adenomas in young patients.
AB  - The expression by non-functioning adenomas (NFoma) of somatostatin receptor
      (SSTR) subtypes and estrogen receptor (ERalpha) is poorly understood.
      Consequently, the mRNAs of SSTR subtypes (SSTR) 1, 2, 3, and 5, dopamine receptor
      (D2R), and ERalpha were measured by real-time quantitative RT-PCR in 59 NFomas
      and 50 functioning adenomas; the latter included 30 GH-secreting adenomas
      (GHomas) and 20 prolactinomas (PRLomas). NFomas expressed higher levels of SSTR3
      than functioning adenomas but had lower levels of SSTR2, SSTR5 and D2R mRNAs than
      GHomas. Their ERalpha levels were higher than those of GHomas. The SSTR subtype
      mRNA levels in NFomas correlated significantly with each other; there was also a
      good correlation between the SSTR subtypes and ERalpha in NFomas. These
      correlations were largely only observed in younger patients (<50 years). The
      present study describes the differential expression of SSTR subtypes in the
      largest number of NFoma patients studied thus far, and further proposes possible
      involvements of SSTR3 and estrogen in the pathophysiology of NFomas.

PMID- 20797423
TI  - C/EBPbeta is AMP kinase sensitive and up-regulates PEPCK in response to ER stress
      in hepatoma cells.
AB  - Diabetes and obesity are associated with activation of endoplasmic reticulum (ER)
      stress; however a direct link between ER stress and increased hepatic
      gluconeogenesis remains unclear. Here we show that ER stress triggers a
      significant increase in expression of CCAAT/enhancer-binding protein (C/EBPbeta)
      and phosphorylated CREB together with reduced phospho-AMP-activated protein
      kinase (pAMPK) in hepatoma cells. ER stress contributed to transcriptional
      activation of the gluconeogenic phosphoenolpyruvate carboxykinase (PEPCK)
      promoter in Huh7 and HepG2 cells via cAMP binding motif (CRE site). Chromatin
      immunoprecipitation assays demonstrate that C/EBPbeta is recruited to the PEPCK
      promoter during ER stress and is reversed by pre-treatment with a JNK inhibitor
      that relieves ER stress. C/EBPbeta but not pCREB was suppressed by the AMPK
      activator AICAR or constitutively active AMPK, while dominant negative AMPK
      increased C/EBPbeta expression. These data suggest that ER stress triggers
      suppression of AMPK while increasing C/EBPbeta and pCREB expression which
      activates PEPCK gene transcription. Understanding how ER stress suppresses AMPK
      activation and increases C/EBPbeta expression could lead to a potentially novel
      pathway for treatment of diabetes.

PMID- 20797425
TI  - The orphan nuclear receptors COUP-TFI and COUP-TFII regulate expression of the
      gonadotropin LHbeta gene.
AB  - Normal sexual development and reproductive function depend on precise temporal
      and quantitative expression of the pituitary gonadotropins, LH and FSH. LHbeta
      subunit gene expression is achieved by transcription factors acting at highly
      conserved and closely spaced cis-elements in the proximal 200 base pairs of the
      promoter. We now demonstrate that LHbeta promoter activity is further regulated
      by the orphan nuclear receptors, chicken ovalbumin upstream promoter
      transcription factors (COUP-TFI and COUP-TFII). These data establish that COUP
      TFs are expressed in primary pituitary gonadotropes and two gonadotrope-derived
      cell lines. COUP-TFs bind to two promoter regions in the LHbeta gene which
      overlap but are distinct from two previously defined cis-elements for another
      orphan nuclear receptor, steroidogenic factor-1 (SF-1). Transient transfection
      studies demonstrated that COUP-TFs stimulate LHbeta gene promoter activity in the
      absence of SF-1, but blunt SF-1-mediated stimulation of gene expression in a
      reporter construct containing both SF-1 cis-elements (GSEs). Evaluation of
      constructs containing mutations or truncations in the GSEs revealed a complex
      pattern of activation and inhibition by COUP-TF on this promoter, suggesting
      multiple mechanisms by which this factor modulates LHbeta gene expression. To our
      knowledge, these data are the first to demonstrate COUP-TF expression and
      function in pituitary gonadotropes.

PMID- 20797426
TI  - Whole blood, flow-chamber studies in real-time indicate a biphasic role for
      thymosin beta-4 in platelet adhesion.
AB  - BACKGROUND: Thymosin beta 4 (Tbeta(4)) is a major actin sequestering peptide
      present in most mammalian cells. It also acts as an anti-inflammatory agent and
      promotes corneal wound healing. METHODS: In the present study, we constructed a
      four channel cylindrical flow chambers out of polydimethylsiloxane (PDMS) on
      microscope coverslips. The platelet-binding proteins-fibrinogen and collagen-were
      immobilized onto the middle ~25% of the inner cylindrical surface. The flow
      method introduced here was employed to determine the effect of Tbeta(4), on the
      deposition of ADP-activated platelets onto fibrinogen cross-linked flow chambers.
      RESULTS: The binding data from the flow chambers indicated that the both the rate
      constant of platelet deposition (average: 0.026+/-0.0015s(-1), corresponding to a
      half-life of 26.7s) and the total number of deposited platelets were independent
      of the platelet binding protein and the activating agent. Our results show that
      low concentrations of Tbeta(4) (0.2 MUM to 0.5 MUM) increased both the rate
      constant of platelet deposition by ~1.5-fold (i.e. half-life decreased from 26.7s
      to 17.6s) and the total number of deposited platelets by ~3-fold. However at
      higher concentrations (>1 MUM) the Tbeta(4)-potentiating effect was diminished to
      near control levels. Tbeta(4) did interact with fibrinogen with an estimated K(D)
      of ~126+/-18nM or 66+/-20nM under equilibrium or flow, respectively. CONCLUSION:
      These results suggest that Tbeta(4) could potentially increase the affinity of
      platelet receptors for their ligands thus promoting platelet deposition. Tbeta(4)
      could also bind to fibrinogen and as its concentration increased would prevent
      platelet-fibrinogen interactions resulting in the attenuation of platelet
      deposition. GENERAL SIGNIFICANCE: This work suggests that Tbeta(4) might have a
      dual role in platelet function.

PMID- 20797427
TI  - Prediction of regulatory networks in mouse abdominal wall.
AB  - Sequence specific transcription factors are essential for pattern formation and
      cell differentiation processes in mammals. The formation of the abdominal wall
      depends on a flawless merge of several developmental fields in time and space.
      The absence of Pitx2 leads to an open abdominal wall in mice, while mutations in
      humans result in umbilical defects, suggesting that a single homeobox
      transcription factor coordinates the formation and patterning of this anatomical
      structure. Gene expression analysis from abdominal tissue including the abdominal
      wall after removal of the major organs, of wild type, Pitx2 heterozygote and
      mutant mice, at embryonic day 10.5, identified 275 genes with altered expression
      levels. Pitx2 target genes were clustered using the "David Bioinformatics
      Functional Annotation Tool" web application, which bins genes according to gene
      ontology (GO) key word enrichment. This provided a way to both narrow the target
      gene list and to start identifying potential gene families regulated by Pitx2.
      Target genes in the most enriched bins were further analyzed for the presence and
      the evolutionary conservation of Pitx2 consensus binding sequence, TAATCY, on the
      -20 kb, intronic and coding gene sequences. Twenty Pitx2 target genes that passed
      all the above criteria were classified as genes involved in cell transport and
      growth. Data from these studies suggest that Pitx2 acts as an inhibitor of
      protein transport and cell apoptosis contributing to the open body wall
      phenotype. This work provides the framework to which the developmental network
      leading to abdominal wall syndromes can be built.

PMID- 20797428
TI  - Resveratrol induces p53 and suppresses myocardin-mediated vascular smooth muscle
      cell differentiation.
AB  - Resveratrol (RSVL), a polyphenolic antioxidant present in red wine, has been
      shown to provide cardiovascular protection by improving endothelial function and
      reducing myocardial ischemia. However, little is known about how RSVL affects
      vascular smooth muscle cells (VSMCs) differentiation. RSVL blocks VSMC
      proliferation in vitro and neointimal formation following artery injury in vivo.
      Thus, one might expect that RSVL will promote VSMC differentiation. Unexpectedly,
      our results in this study show that RSVL induces VSMCs phenotypic modulation;
      this is characterized by suppressed transcription of SMC-specific marker genes
      Tagln, Acta2, Myh11, and Smtn in a dose-dependent and time-dependent manner in
      cultured VSMCs. Consistent with previous studies, RSVL induces the nuclear
      translocation of p53 and the expression of p53-responsive genes such as Cdkn1a,
      Gadd45a, Gadd45, and Fas. In an effort to identify the molecular mechanisms
      whereby RSVL represses VSMC differentiation, we found that RSVL inhibits the
      transcription of Myocardin (myocd) and Srf, the key VSMC transcriptional
      regulators. However, knockingdown and overexpressing p53 did not affect RSVL
      induced VSMCs phenotypic modulation: this suggests that RSVL may induce VSMC
      dedifferentiation via p53-independent mechanisms. This study provides the first
      evidence showing that RSVL induces VSMC dedifferentiation by regulating Myocardin
      and SRF-mediated VSMC gene transcription.

PMID- 20797430
TI  - Enhanced discrimination of single nucleotide polymorphisms using 3' nucleotide
      differences in ligase detection reaction probes.
AB  - The ligase detection reaction (LDR) is a highly specific genotyping method for
      single nucleotide variations. Although LDR typically discriminates single
      nucleotide polymorphism (SNP) alleles at the 3' end of so-called LDR
      discriminating probes, we designed probes in which the position of nucleotide
      differences for discrimination was shifted to the second and third nucleotides
      from the 3' end. Using the 3'-modified probes, we targeted SNPs of the human ABO
      group and investigated the specificity and efficiency of ligation by a universal
      LDR assay. We demonstrated that one or two nucleotide shifts of differences in
      discriminating probes improve the allele balance in detecting both base
      substitutions and short deletions. In regard to short deletions, moreover, the
      shifts of nucleotide differences in discriminating probes form the perfect
      machted or multiple-mismatched structures (the bulge structures) in the
      discriminating probe-target DNA duplex and may contribute to enhance ligation
      efficiency.

PMID- 20797431
TI  - An integrated bioinformatics approach to the characterization of influenza A/H5N1
      viral sequences by microarray data: Implication for monitoring H5N1 emerging
      strains and designing appropriate influenza vaccines.
AB  - In order to characterize A/H5N1 viral sequences, a bioinformatics approach
      accurately identified viral sequences from discovery of a sequence signature,
      which provided enough distinctive information for sequence identification. Eight
      highly pathogenic H5N1 viral isolations were collected from different areas of
      Thailand between 2003 and 2006, and were used for analysis of H5N1 genotypic
      testing with a semiconductor-based oligonucleotide microarray. All H5N1 samples
      and H1N1, H4N8 negative controls were correctly subtyped. Sensitivity of the
      eight oligonucleotide probes, with optimized cut-offs, ranged from 70% (95% CI 65
      75) to 87% (95% CI 84-91), and the corresponding Kappa values ranged from 0.76
      (95% CI 0.72-0.80) to 0.86 (95% CI 0.83-0.89). Semi-conductor-based
      oligonucleotide array and oligonucleotide probes corresponded well when detecting
      H5N1. After fully correcting the subtype from the result of microarray signal
      intensity, the microarray output method combined with bioinformatics tools,
      identified and monitored genetic variations of H5N1. Capability of distinguishing
      different strains of H5N1 from Thailand was the outstanding feature of this
      assay. Ninety percent of HA and NA (4/5) genes were sequenced correctly, in
      accordance with previous examinations performed by classical diagnostic methods.
      The low-medium-high bioinformatics resolutions were able to predict an epidemic
      strain of H5N1. This study also showed the advantage of using a large genotypic
      database to predict the epidemic strain of H5N1. However, the monitoring protocol
      of this new strain has been recommended for further study with a large-scale
      sample.

PMID- 20797429
TI  - Insights into the neurodevelopmental origin of schizophrenia from postmortem
      studies of prefrontal cortical circuitry.
AB  - The hypothesis that schizophrenia results from a developmental, as opposed to a
      degenerative, process affecting the connectivity and network plasticity of the
      cerebral cortex is supported by findings from morphological and molecular
      postmortem studies. Specifically, abnormalities in the expression of protein
      markers of GABA neurotransmission and the lamina- and circuit-specificity of
      these changes in the cortex in schizophrenia, in concert with knowledge of their
      developmental trajectories, offer crucial insight into the vulnerability of
      specific cortical networks to environmental insults during different periods of
      development. These findings reveal potential targets for therapeutic
      interventions to improve cognitive function in individuals with schizophrenia,
      and provide guidance for future preventive strategies to preserve cortical
      neurotransmission in at-risk individuals.

PMID- 20797432
TI  - Carbon monoxide-releasing molecule CORM-3 suppresses vascular endothelial cell
      SOD-1/SOD-2 activity while up-regulating the cell surface levels of SOD-3 in a
      heparin-dependent manner.
AB  - The role of CO in the modulation of antioxidant enzyme function has not been
      investigated, yet. In this study we assessed the effects and potential mechanisms
      of the ruthenium-based water-soluble CO-releasing molecule CORM-3 in the
      modulation of superoxide dismutase (SOD) activity/binding in vascular endothelial
      cells (HUVECs). To this end, HUVECs were treated with CORM-3 (100 MUM) and
      assessed for total SOD activity in cell lysates (cell-associated SOD activity)
      and cell culture supernatants (soluble SOD). In parallel, release/binding of
      extracellular SOD (SOD-3) in the absence or presence of heparin (1-10 IU/ml), a
      key factor regulating SOD-3 cell-surface binding, was investigated. In addition,
      the effects of CORM-3 on the modulation of purified SOD-1 and SOD-2 activity in a
      cell-free system were also assessed. The results obtained indicate that CORM-3
      effectively suppresses the activity of both purified SOD-1 and SOD-2. These
      findings were accompanied by CORM-3-dependent attenuation of total cell
      associated SOD activity (without affecting SOD-1/SOD-2 protein expression) and a
      subsequent increase in ROS production (DHR123 oxidation) in HUVECs. In parallel,
      a concomitant increase in soluble-SOD activity (due to increased SOD-3 release
      from the cell surface) was observed in the cell culture supernatants. However, in
      the presence of heparin, total cell-associated SOD activity was significantly
      increased by CORM-3, because of increased binding of SOD-3 to HUVECs. Taken
      together these findings indicate for the first time that CORM-3 modulates both
      the activity of intracellular SOD (i.e., SOD-1 and SOD-2) and the binding of
      extracellular SOD (SOD-3) to the cell surface.

PMID- 20797433
TI  - Inhalable powder formulation of vasoactive intestinal peptide derivative,
      [R15,20,21, L17]-VIP-GRR, attenuated neutrophilic airway inflammation in
      cigarette smoke-exposed rats.
AB  - Cigarette smoke (CS) has been identified as a predominant causative factor for
      chronic obstructive pulmonary disease (COPD), so CS-exposed rodent model of COPD
      has drawn considerable interest and attention for fundamental study and drug
      discovery. In the present study, using experimental COPD model rats, the
      therapeutic potential of a newly prepared respirable powder (RP) formulation of a
      long-acting VIP derivative, [Arg(15,20,21), Leu(17)]-VIP-GRR (IK312532), was
      assessed with a focus on pro-inflammatory biomarkers, morphological and
      histochemical changes, and infiltrated cells in the respiratory system. CS
      exposure of rats for 11 days led to the marked infiltration of inflammatory
      cells, except for eosinophils, in bronchiolar epithelium, followed by goblet cell
      metaplasia and hyperplasia. However, inhalation of IK312532-RP (50MUg/rat) in the
      CS-exposed rats resulted in 74 and 71% reductions of granulocyte recruitment in
      bronchoalveolar lavage fluids and lung tissues, respectively, with 68% decrease
      of goblet cells. Biomarker study demonstrated that the inhaled IK312532-RP could
      suppress the CS-evoked increase of myeloperoxidase in both plasma and lung by 87
      and 70%, respectively, possibly leading to potent suppression of neutrophilic
      inflammatory symptoms. The results from TUNEL staining were indicative of
      apoptotic damage in respiratory tissues of the CS-exposed rats, and there
      appeared to be marked decrease of TUNEL-positive cells in the CS-exposed rat with
      inhaled IK312532-RP. The present findings suggest that an inhalable formulation
      of IK312532 might be efficacious as a therapy for COPD or other airway
      inflammatory diseases because of its potent immunomodulating activities.

PMID- 20797434
TI  - Glucuronidation of racemic O-desmethyltramadol, the active metabolite of
      tramadol.
AB  - O-Desmethyltramadol, the active metabolite of analgesic tramadol, is metabolised
      through glucuronidation. The present study was conducted to identify the human
      UDP-glucuronosyltransferases (UGTs) that catalyse the glucuronidation of O
      desmethyltramadol, a racemic mixture of 1R,2R- and 1S,2S-enantiomers. We
      developed a fast and selective liquid chromatography-mass spectrometry method to
      separate, analyse and quantify the diastereomeric phenolic O-glucuronides of O
      desmethyltramadol. To quantify O-desmethyltramadol glucuronidation, we
      biosynthesised both phenolic O-glucuronides of O-desmethyltramadol and verified
      their structure by mass spectrometry and nuclear magnetic resonance spectroscopy.
      Subsequently, the 16 human UGTs of subfamilies 1A and 2B were screened for O
      desmethyltramadol glucuronidation activity. UGTs 1A7-1A10 exhibited a strict
      stereoselectivity, exclusively glucuroniding the 1R,2R-enantiomer. Similar though
      not strict enantioselectivity was exhibited by UGT2B15. UGT2B7, on the other
      hand, glucuronidated both O-desmethyltramadol enantiomers, with slight preference
      for 1S,2S-O-desmethyltramadol. Enzyme kinetic parameters were determined for the
      most active UGTs, 1A8 and 2B7. The apparent K(m) or S(50) values were high:
      1.2mM+/-0.23 for 1R,2R-O-desmethyltramadol with UGT1A8 and 1.84+/-1.2 and 4.6+/
      2.0mM for 1S,2S- and 1R,2R-O-desmethyltramadol enantiomers with UGT2B7,
      respectively. Glucuronidation analyses of O-desmethyltramadol with human liver
      microsomes exhibited stereoselectivity, favouring the 1S,2S-O-desmethyltramadol
      over 1R,2R-O-desmethyltramadol and yielding 62.4 and 24.6pmol/mg/min,
      respectively. In intestinal microsomes, on the other hand, the two enantiomers
      were glucuronidated at similar rates, about 6pmol/mg/min. The results shed new
      light on both tramadol metabolism and the substrate selectivity of the human
      UGTs.

PMID- 20797435
TI  - In vitro capturing of various lipophilic illicit drugs by lipid dispersions. An
      electrokinetic capillary chromatography and fluorescence polarization study.
AB  - Fatal drug overdoses are a cause for concern all over the world. We present here
      a lipid-based formulation which has a strong affinity for some common illicit
      street drugs and can be used in vivo as a lipid 'sink'. In this study, the in
      vitro interactions of nine lipophilic drugs and three lipid dispersions were
      determined by electrokinetic capillary chromatography and fluorescence
      polarization. Two lipid dispersions, zwitterionic 1-palmitoyl-2-oleyl-sn-glycero
      3-phosphocholine (POPC) and an anionic mixture of POPC and 1-palmitoyl-2-oleyl-sn
      glycero-3-[phospho-rac-(1-glycerol)] (POPG) were tested and compared with a
      commercial lipid dispersion Intralipid((r)), which has been successfully used for
      resuscitation of patients in cases of anesthetic overdoses. The interactions
      between dispersions and the drugs were quantified by means of retention factors
      and distribution constants, which makes the results highly comparable to those
      obtained from any other formulation of lipids. The results demonstrate a stronger
      interaction between the drugs and an artificial liposome dispersion than with the
      commercial Intralipid dispersion. The liposome dispersion composed of POPC and
      POPG functions as a lipid 'sink' for efficient entrapment of various lipophilic
      drugs.

PMID- 20797436
TI  - New cell culture models of hepatitis C virus entry, replication, and virus
      production.

PMID- 20797437
TI  - Formulation and in vitro evaluation of highly dispersive insulin dry powder
      formulations for lung administration.
AB  - The aim of this work was to develop highly dispersible and dry formulations of
      insulin for use in dry powder inhalers (DPIs) using high-pressure homogenisation
      (HPH) and spray-drying. Several formulations were evaluated, including
      formulations spray-dried without excipients and formulations coated with lipids.
      A physiological lipid composition based on a mixture of cholesterol and
      phospholipids was used to form the coating film around micronised drug particles.
      The production technique and excipients were chosen in order to limit the
      degradation of the active ingredient. The resulting powders exhibited a size and
      shape suitable for the deep lung deposition of drugs, and good aerodynamic
      features were obtained for the different formulations tested, with fine particle
      fractions between 46% and 63% vs. 11% for raw insulin powder. The presence of a
      lipid coating of up to 30% (w/w) did not significantly affect the aerodynamic
      behaviour, and the coated formulations also exhibited a decreased residual
      moisture content of between 2.3% and 3.7% vs. 4.8% for raw insulin, which should
      improve the long-term stability of the protein formulations. No degradation of
      the insulin molecule occurred during the HPH/spray-drying process, as it was
      shown using an HPLC method (insulin content between 98.4% and 100.5%), and the
      content in high molecular weight proteins, assessed using a gel filtration
      method, stayed below 0.4%.

PMID- 20797438
TI  - Extracellular matrix-derived products modulate endothelial and progenitor cell
      migration and proliferation in vitro and stimulate regenerative healing in vivo.
AB  - Most adult mammals heal without restorative replacement of lost tissue and
      instead form scar tissue at an injury site. One exception is the adult MRL/MpJ
      mouse that can regenerate ear and cardiac tissue after wounding with little
      evidence of scar tissue formation. Following production of a MRL mouse ear hole,
      2mm in diameter, a structure rapidly forms at the injury site that resembles the
      amphibian blastema at a limb amputation site during limb regeneration. We have
      isolated MRL blastemal cells (MRL-B) from this structure and adapted them to
      culture. We demonstrate by RT-PCR that even after continuous culturing of these
      cells they maintain expression of several progenitor cell markers, including DLK
      (Pref-1), and Msx-1. We have isolated the underlying extracellular matrix (ECM)
      produced by these MRL-B cells using a new non-proteolytic method and studied the
      biological activities of this cell-free ECM. Multiplex microELISA analysis of MRL
      B cell-free ECM vs. cells revealed selective enrichment of growth factors such as
      bFGF, HGF and KGF in the matrix compartment. The cell-free ECM, degraded by mild
      enzyme treatment, was active in promoting migration and proliferation of
      progenitor cells in vitro and accelerating wound closure in a mouse full
      thickness cutaneous wound assay in vivo. In vivo, a single application of MRL-B
      cell matrix-derived products to full thickness cutaneous wounds in non
      regenerative mice, B6, induced re-growth of pigmented hair, dermis and epidermis
      at the wound site whereas scar tissue replaced these tissues at wound sites in
      mice treated with vehicle alone. These studies suggest that matrix-derived
      products can stimulate regenerative healing and avert scar tissue formation in
      adult mammals.

PMID- 20797439
TI  - Hysteretic swelling of wood at cellular scale probed by phase-contrast X-ray
      tomography.
AB  - We investigated the three-dimensional, microscopic, dimensional changes of Picea
      abies (L. Karst) wood samples due to controlled steps of the ambient relative
      humidity. The study was performed at the wood cellular scale by high-resolution
      synchroton radiation phase-contrast X-ray tomographic microscopy (srPCXTM).
      Tomographic images were taken after the samples achieved moisture equilibrium at
      five adsorption and four desorption steps. For spruce latewood, swelling and
      shrinkage are found to be larger, more hysteretic and more homomorphic than for
      earlywood. Furthermore, while latewood undergoes similar strains in the
      transverse directions, earlywood radial strains are less than a third of the
      tangential strains. The less homomorphic and smaller swelling/shrinkage of
      earlywood in radial direction is found to be caused by the presence of rays.

PMID- 20797440
TI  - Native architecture of the photosynthetic membrane from Rhodobacter veldkampii.
AB  - The photosynthetic membrane in purple bacteria contains several pigment-protein
      complexes that assure light capture and establishment of the chemiosmotic
      gradient. The bioenergetic tasks of the photosynthetic membrane require the
      strong interaction between these various complexes. In the present work, we
      acquired the first images of the native outer membrane architecture and the
      supramolecular organization of the photosynthetic apparatus in vesicular
      chromatophores of Rhodobacter (Rb.) veldkampii. Mixed with LH2 (light-harvesting
      complex 2) rings, the PufX-containing LH1-RC (light-harvesting complex 1-
      reaction center) core complexes appear as C-shaped monomers, with random
      orientations in the photosynthetic membrane. Within the LH1 fence surrounding the
      RC, a remarkable gap that is probably occupied (or partially occupied) by PufX is
      visualized. Sequence alignment revealed that one specific region in PufX may be
      essential for PufX-induced core dimerization. In this region of ten amino acids
      in length all Rhodobacter species had five conserved amino acids, with the
      exception of Rb. veldkampii. Our findings provide direct evidence that the
      presence of PufX in Rb. veldkampii does not directly govern the dimerization of
      LH1-RC core complexes in the native membrane. It is indicated, furthermore, that
      the high membrane curvature of Rb. veldkampii chromatophores (Rb. veldkampii
      features equally small vesicular chromatophores alike Rb. sphaeroides) is not due
      to membrane bending induced by dimeric RC-LH1-PufX cores, as it has been proposed
      in Rb. sphaeroides.

PMID- 20797441
TI  - The power of imagination--how anticipatory mental imagery alters perceptual
      processing of fearful facial expressions.
AB  - Expectancies strongly shape our perception of the world and preconceptions about
      stimulus characteristics can even bias the sensory system for illusory percepts.
      Here we assessed with functional magnetic resonance imaging how anticipatory
      mental imagery of a mildly fearful face created a predictive bias that
      proactively altered perception of highly fearful faces and generated the
      "illusion" of reduced fearfulness. We found that anticipatory activation of the
      fusiform gyrus (FG) was modulated by the fearfulness of the imagined face.
      Further during anticipatory imagery, regulatory influences from the lateral and
      ventromedial prefrontal cortex on the FG primed the perceptual system for a
      subsequent misperception. This was achieved by increasing perceptual activation
      in higher-order brain regions for the evaluation of affective valence and
      contextual framing, while at the same time restricting bottom-up arousal and
      attention to fearful expressions. Anticipatory mental imagery may thus represent
      an effective antecedent strategy through which emotional perception can be
      significantly altered.

PMID- 20797442
TI  - Origin and evolution of endemic Galapagos Varronia species (Cordiaceae).
AB  - Four endemic Varronia species (Cordiaceae) occupy the Galapagos archipelago.
      Three comprise the V. leucophlyctis complex (V. anderssonii, V. leucophlyctis, V.
      scouleri), whose species' limits are not well defined but that is morphologically
      distinct from the fourth endemic species, V. revoluta. Sequence data from the
      nuclear rDNA ITS region and the cpDNA ndhF gene were gathered from 49 accessions
      of Varronia from five Galapagos islands in order to test the evolutionary
      relationships of endemic Varronia species, determine the number of immigration
      events to the islands and estimate their age of origin. All endemic species nest
      within the clade of species belonging to Varronia, which is an entirely American
      genus. We find little evidence of phylogenetic structuring of the V.
      leucophlyctis complex but divergent phylogenetic signals from nuclear and
      chloroplast genomes regarding its relationship to V. revoluta. Results are
      consistent with a hybridization event involving ancestral Galapagean lineages,
      with chloroplast and nuclear data suggesting one or two dispersal events from the
      Americas to the Galapagos, respectively. Fossil-based divergence time estimates
      indicate endemic species diverged from American continental species as early as
      4.5 Myr ago and radiated 1.12 Myr, which coincides with ages of exposed and
      subsided Galapagos islands.

PMID- 20797443
TI  - A novel and non-destructive method to examine meniscus architecture using 9.4
      Tesla MRI.
AB  - OBJECTIVE: To investigate the ability of high-field (9.4 T) magnetic resonance
      (MR) imaging to delineate porcine knee meniscal tissue structure and meniscal
      tears. MATERIALS AND METHODS: Porcine knees were obtained from a local abattoir,
      and eight medial menisci with no visible defects were dissected. Lesions
      simulating longitudinal tears were created on two of the menisci. MR images of
      the menisci were obtained at 9.4 T using a three-dimensional (3D)-FLASH sequence.
      A detailed 3D internal architecture of the intact and injured menisci was
      demonstrated on high-resolution MR images. RESULTS: High-resolution 3D MR imaging
      allowed visualisation of internal architecture of the meniscus and disruption to
      the internal structural network in damage models. The architecture of the porcine
      knee meniscus revealed by the MR scans appeared similar to the structures
      visualised by histology in previously reported studies. CONCLUSION: High-field
      MRI is a non-destructive technique to examine the internal structural components
      and damage/wear of meniscal tissue. It has tremendous potential in the field of
      functional cartilage/meniscus biomechanics and biotribology.

PMID- 20797445
TI  - Genetic alterations for increased coumarin production lead to metabolic changes
      in the medicinally important Pelargonium sidoides DC (Geraniaceae).
AB  - The medicinal plant Pelargonium sidoides is fast becoming threatened due to the
      overharvest of its tubers from the wild to produce a phytopharmaceutical for
      treating respiratory infections. The action of the coumarins is implicated in the
      efficacy of the commercial herbal extract with the highly oxygenated coumarins
      exhibiting the best anti-bacterial and anti-viral activity. Through this work we
      aimed at exploring the metabolic effects of Agrobacterium rhizogenes
      transformation. After confirmation of transgenesis using PCR amplification of the
      rol A (320 bp), rol B (400 bp) and rol C (600 bp) genes, metabolite profiles
      indicated a high level of variability between the different transgenic clones but
      these had more compounds compared to non-transgenic control cultures. This was
      represented by a two- to four-fold increase in detected metabolites in transgenic
      clones. We quantified several commercially important coumarins, flavonoids and
      phenolic acids. One of the clones had six out of nine of these metabolites.
      Overall, the concentration of these metabolites of interest were significantly
      changed in transgenic root cultures, for instance shikimic acid was recorded at
      the highest level in clone A4T-A. Production of key metabolites at significantly
      higher concentrations due to transgenesis and positive anti-bacterial activity
      exhibited by transgenic roots lends support to the idea of developing these
      clones as an alternative source that will allow for sustainable access to
      economically valuable secondary compounds of P. sidoides.

PMID- 20797444
TI  - Comparison of transcriptional and translational changes caused by long-term
      menadione exposure in Aspergillus nidulans.
AB  - Under long-term oxidative stress caused by menadione sodium bisulfite, genome
      wide transcriptional and proteome-wide translational changes were compared in
      Aspergillus nidulans vegetative cells. The comparison of proteomic and DNA
      microarray expression data demonstrated that global gene expression changes
      recorded with either flip-flop or dendrimer cDNA labeling techniques supported
      proteome changes moderately with 40% and 34% coincidence coefficients,
      respectively. Enzyme levels in the glycolytic pathway were alternating, which was
      a direct consequence of fluctuating gene expression patterns. Surprisingly,
      enzymes in the vitamin B2 and B6 biosynthetic pathways were repressed
      concomitantly with the repression of some protein folding chaperones and nuclear
      transport elements. Under long-term oxidative stress, the peroxide-detoxifying
      peroxiredoxins and cytochrome c peroxidase were replaced by thioredoxin
      reductase, a nitroreductase and a flavohemoprotein, and protein degradation
      became predominant to eliminate damaged proteins.

PMID- 20797446
TI  - Effects of galactose on direct and indirect pathway estimates of hepatic glycogen
      synthesis.
AB  - Hepatic glycogen is formed by direct and indirect pathways whose activities
      reflect altered nutrition or disease. Direct/indirect pathway measurements often
      involve test meals where ~ 10% of carbohydrate is galactose, but its effects on
      direct/indirect pathway estimates are unknown. Therefore, direct/indirect pathway
      contributions in 24-h fasted rats given 2g/kg 100% glucose (GLU, n=6) or 90%
      glucose-10% galactose (GLU+GAL, n=6) were measured by [U-(13)C]glucose dilution
      and by position-5/position-2 glycogen enrichment (H5/H2) from 2H(2)O. For
      GLU+GAL, galactose glycogenesis was independently measured with [1
      (13)C]galactose. Glycogenesis was equivalent in both groups but for GLU+GAL, 23
      +/- 4% of glycogen was derived from galactose. [U-(13)C]glucose reported a 30 +/-
      3% direct pathway contribution to glycogenesis for GLU but only 20 +/- 3% for
      GLU+GAL (p=0.012 vs. GLU). H5/H2 yielded identical direct pathway estimates (32
      +/- 3% GLU, 29 +/- 6% GLU+GAL). Thus, galactose glycogenesis was undetected by
      H5/H2 while [U-(13)C]glucose reported a reduced direct/indirect pathway ratio.
      With [1-(13)C]galactose also present, correct glycogenic source contributions
      were obtained.

PMID- 20797447
TI  - Altered signal transduction pathways and induction of autophagy in human myotonic
      dystrophy type 1 myoblasts.
AB  - Congenital myotonic dystrophy type 1 (CDM1) affects patients from birth and is
      associated with mental retardation and impaired muscle development. CDM1 patients
      carry 1000-3000 CTG repeats in the DMPK gene and display defective skeletal
      muscles differentiation, resulting in reduced size of myotubes and decreased
      number of satellite cells. In this study, human myoblasts in culture deriving
      from control and DM1 embryos (3200 CTG repeats) were analyzed using both a
      biochemical and electron microscopic approach, in order to provide new insights
      into the molecular mechanisms underlying such alteration. Interestingly, electron
      microscopy analysis showed not only ultrastructural features of abnormal
      differentiation but also revealed the presence of autophagic vacuoles in DM1
      myoblasts not undergoing differentiation. In accordance with the electron
      microscopic findings, the autophagic markers LC3 and ATG5, but not apoptotic
      markers, were significantly up regulated in DM1 myoblasts after differentiating
      medium addition. The induction of autophagic processes in DM1 myoblasts was
      concomitant to p53 over-expression and inhibition of the mTOR-S6K1 pathway,
      causatively involved in autophagy. Moreover biochemical alterations of the two
      main signal transduction pathways involved in differentiation were observed in
      DM1 myoblasts, in particular decreased activation of p38MAPK and persistent
      activation of the MEK-ERK pathway. This work, while demonstrating that major
      signaling pathways regulating myoblasts differentiation are profoundly deranged
      in DM1 myoblasts, for the first time provides evidence of autophagy induction,
      possibly mediated by p53 activation in response to metabolic stress which might
      contribute to the dystrophic alterations observed in the muscles of congenital
      DM1 patients.

PMID- 20797448
TI  - Hypoxia-induced metabolic shifts in cancer cells: moving beyond the Warburg
      effect.
AB  - Hypoxia has been recognized to play a role in promoting the invasive and
      metastatic behaviour of cancer cells. Largely via the transcription factor,
      hypoxia-induced factor 1, hypoxia exerts significant effects on cellular
      metabolism, with numerous downstream consequences. Energetically there is a
      significant shift away from oxidative phosphorylation in mitochondria towards
      glycolysis, a state also involved in the 'Warburg effect'. The proteins involved
      in mediating the altered metabolic pathways seen in tumour cells thus represent
      new targets for potential therapeutic intervention. Hypoxia has been associated
      with the development of aggressive phenotypes in cancer cells, and can be
      accompanied by changes in carbohydrate and lipid metabolism that impact tumour
      cell proliferation, adhesion, and angiogenesis. Herein, we examine glycolytic and
      other less investigated metabolic pathways in relation to cancer and hypoxia,
      with a focus on emerging tools for large-scale metabolite profiling
      ('metabolomics'). Metabolomic technologies permit the measurement of a wide range
      of metabolites in an untargeted manner, however, to date, this technology has
      been relatively under utilized for studying cellular responses to hypoxia. We
      detail some of the common experimental approaches employed in metabolomics
      experiments, including nuclear magnetic resonance and new mass spectrometry-based
      methods of analysis. Selected examples of the application of these technologies
      to the study of metabolic alterations brought about by hypoxia are provided,
      particularly as they relate to energy, carbohydrate, and lipid metabolism.
      Finally, the potential for therapeutic targeting of metabolic processes activated
      by hypoxia is presented.

PMID- 20797449
TI  - Recruitment of infants with sickle cell anemia to a Phase III trial: data from
      the BABY HUG study.
AB  - BACKGROUND: Protocol-eligible subjects may not be candidates for research
      participation or may decline. To determine factors that affected accrual, we
      evaluated enrollment in BABY HUG, a multi-center, randomized, placebo-controlled
      Phase III trial of hydroxyurea (HU) in infants with sickle cell anemia. METHODS:
      An anonymized registry of potential subjects served as the primary source of
      data. Study coordinators considered all infants less than age 18 months with a
      hemoglobin FS diagnosis on newborn screening. Data included the number of
      potentially eligible subjects, whether parents were approached, and reasons for
      participating or declining. RESULTS: Of 1106 potential participants, 28% were not
      approached for reasons such as prior poor adherence to clinical care. Interested
      families expressed willingness to contribute to medical knowledge (51%), hope of
      being randomized to receive hydroxyurea (51%), and desire for closer clinical
      care (51%) as reasons for participating. Disease severity or the perception that
      their child was ill had less impact on willingness to participate (16%). Parents
      who declined cited fear of research (19%), transportation problems (14%), and the
      demanding nature of the study (25%). Ultimately, 234 (21%) gave informed consent,
      with little variability of acceptance rates among sites. Importantly, the number
      of subjects enrolled correlated with the number of families that were approached.
      Sites that excluded patients based on clinical/psychosocial biases were not more
      successful in recruiting than those who approached all eligible subjects.
      CONCLUSION: Large, demanding clinical trials require an adequate pool of
      potential participants. Approaching all potentially eligible patients without
      predetermined biases enhances success in recruitment.

PMID- 20797450
TI  - Reactive oxygen species signaling in pulmonary vascular smooth muscle.
AB  - In recent years, it has become evident that reactive oxygen species (ROS) play a
      critical role in the regulation of several physiological and pathophysiological
      processes. Herein we review the main sources, targets and pathophysiological
      roles of ROS in pulmonary vascular smooth muscle. Mitochondria and NADPH oxidases
      represent the major sources of ROS in vascular cells. In addition, ROS can be
      produced by different pathways of arachidonic acid metabolism, endothelial NO
      synthase (eNOS) and xantine oxidase. There is increasing evidence for the role of
      ROS, specially hydrogen peroxide, as signaling moieties to induce increase in
      intracellular calcium concentration ([Ca2+]i) and contraction in pulmonary artery
      smooth muscle cells (PASMC) through the modulation of a variety of targets, such
      as Rho kinases (ROCK), protein kinase C (PKC), voltage-gated potassium K+ (Kv)
      channels and ryanodine receptors (RyR). Thus, an increase in ROS has been
      reported to contribute to the responses induced by different vasoconstrictor
      stimuli, including hypoxia. Finally, results from recent studies highlighting the
      involvement of ROS in the development of pulmonary hypertension are discussed in
      the present paper.

PMID- 20797451
TI  - Postnatal changes in the cardiorespiratory response and ability to
      autoresuscitate from hypoxic and hypothermic exposure in mammals.
AB  - Most mammals are born immature and a great deal of maturational changes must
      occur early in the early postnatal life to prepare for life as an adult. In
      addition to the obvious changes such as physical and musculoskeletal growth, a
      myriad of physiological changes including the cardiorespiratory responses to
      hypoxia and hypothermia must also occur. The most intriguing developmental effect
      is perhaps the change in the ability to autoresuscitate, or spontaneous recovery
      from cardiorespiratory arrest induced by extreme hypoxia or hypothermia. For
      decades the ability of young animals to autoresuscitate from cardiorespiratory
      arrest induced by hypoxic or hypothermic exposure has been documented. In some
      mammalian species, including rats and humans, this ability is lost over
      development while others retain this ability. This review will examine the
      changes that occur in the cardiorespiratory response to hypoxia and hypothermia
      and the change to the ability to autoresuscitate from cardiorespiratory arrest
      over early postnatal development. Furthermore, the review will explore some of
      the potential neuroanatomical, neurochemical and neurophysiological changes
      during early postnatal development that might contribute to the altered reflex
      response to hypoxia and hypothermia and the ability to autoresuscitate.

PMID- 20797452
TI  - Kinetic crystallography by Raman microscopy.
AB  - Raman spectra, obtained using a Raman microscope, offer a unique and incisive
      approach to follow interactions and reactions inside a single crystal under soak
      in or soak-out conditions. The utility of this approach derives from the finding
      that the Raman spectra from single macromolecular crystals, under normal (non
      resonance) conditions, are extremely stable, with a low "light background," and
      provide ideal platforms for Raman difference spectroscopy. In turn, this allows
      the interrogation of sub-molecular changes in very large and complex
      macromolecular environments. There is often great synergy with X-ray
      crystallography, with the Raman spectroscopist providing crystallography
      colleagues with the best soak-in conditions to generate a targeted intermediate
      for flash freezing and X-ray analysis. On the other hand, X-ray structures at
      points along a reaction pathway provide invaluable benchmarks for interpreting
      the Raman data from populations seen by Raman to be changing in real-time. These
      principles will be illustrated by two reactions: the first involves a complex,
      branching reaction pathway underlying the inhibition of beta-lactamases by
      clinically important pharmaceutical compounds, where different combinations of
      drug and enzyme function in different regions of the pathway. The second shows
      how temporal data can be derived for several events in the initiation step of RNA
      synthesis-more specifically, when one GTP molecule is joined to one ATP molecule
      to form a G?A dimer in the active site of a 115,000 Dalton crystalline RNA
      polymerase. Finally, we will summarize the extension of Raman microscopy to
      nucleic acid crystals and the information that has been obtained for RNA-based
      enzymes. This article is part of a Special Issue entitled: Protein Structure and
      Function in the Crystalline State.

PMID- 20797453
TI  - Protein dynamics and ligand migration interplay as studied by computer
      simulation.
AB  - Since proteins are dynamic systems in living organisms, the employment of
      methodologies contemplating this crucial characteristic results fundamental to
      allow revealing several aspects of their function. In this work, we present
      results obtained using classical mechanical atomistic simulation tools applied to
      understand the connection between protein dynamics and ligand migration. Firstly,
      we will present a review of the different sampling schemes used in the last years
      to obtain both ligand migration pathways and the thermodynamic information
      associated with the process. Secondly, we will focus on representative examples
      in which the schemes previously presented are employed, concerning the following:
      i) ligand migration, tunnels, and cavities in myoglobin and neuroglobin; ii)
      ligand migration in truncated hemoglobin members; iii) NO escape and
      conformational changes in nitrophorins; iv) ligand selectivity in catalase and
      hydrogenase; and v) larger ligand migration: the P450 and haloalkane dehalogenase
      cases. This article is part of a Special Issue entitled: Protein Dynamics:
      Experimental and Computational Approaches.

PMID- 20797454
TI  - A measles and rubella (MR) catch-up vaccination campaign in an Egyptian
      University: vaccine uptake and knowledge and attitudes of students.
AB  - INTRODUCTION: In 2008, following a rubella epidemic, the Egyptian Ministry of
      Health implemented a Measles Rubella (MR) catch-up campaign, based on WHO
      recommendations for supplementary immunization activities to eliminate measles by
      2010. The age group targeted was 10-20 years. This campaign was unique in Egypt
      as it was the first national vaccination campaign which included university
      students. AIM: To report uptake of MR vaccine and reasons for declining the
      vaccine among medical and non-medical students in the campaign and to assess the
      knowledge about the vaccine and the diseases. METHODS: The study was conducted in
      two stages. In the first stage during the vaccination sessions, medical and other
      students (N=310) were given a questionnaire to assess their knowledge of the
      campaign and the vaccine. The second stage (N=341) was carried out when the
      campaign was completed to assess vaccine uptake among medical students. RESULTS:
      Posters displayed inside the university were reported to be the main source of
      information about the campaign. Students were generally poorly informed about
      both vaccine adverse effects, and contraindications although medical students
      tended to be better informed than other students. Overall 64.8% medical students
      accepted the vaccine with higher uptake among females than males (85.9 and 58.3%
      respectively). Non-compliant students had a significantly higher mean age. Almost
      half of students who did not accept the vaccine gave their reason as having
      little information about the vaccine (43.3%). CONCLUSION: The MR campaign in Ain
      Shams University may have been more successful with better use of health
      education messages.

PMID- 20797455
TI  - Enterovirus 71 virus-like particle vaccine: improved production conditions for
      enhanced yield.
AB  - To develop the enterovirus 71 (EV71) vaccine, we previously constructed a
      recombinant baculovirus (Bac-P1-3CD) co-expressing EV71 P1 (under polyhedrin
      promoter) and 3CD (under p10 promoter) proteins, which caused P1 cleavage by 3CD
      protease and self-assembly of virus-like particles (VLPs) in Sf-9 cells. Assuming
      that reducing the 3CD expression can alleviate the competition with P1 expression
      and elevate the VLPs yield, hereby we constructed Bac-P1-C3CD and Bac-P1-I3CD
      expressing 3CD under weaker CMV and IE-1 promoters, respectively. Western blot
      and ELISA analyses revealed that Bac-P1-C3CD and Bac-P1-I3CD led to the VLPs
      release into the supernatant and enhanced the extracellular VLPs yield in Sf-9
      cells, but gave poor VLPs production in High FiveTM (Hi-5) cells. By optimizing
      the process parameters including host cells, cell density, culture mode and
      dissolved oxygen (DO), the best extracellular VLPs yield was achieved by
      infecting Sf-9 cells (4 * 10(6)cells/mL) cultured in the bioreactor (DO=30%) with
      Bac-P1-C3CD, which approached ~64.3mg/L and represented a ~43-fold increase over
      the yield (1.5mg/L) attained using the old process (Bac-P1-3CD infection of Sf-9
      cells in the spinner flasks). The resultant VLPs not only resembled the VLPs
      produced from Bac-P1-3CD infection in density, size and shape, but also induced
      potent antibody responses in mouse models. The antibodies neutralized EV71
      strains of homologous and heterologous genogroups, implicating the potential of
      the VLPs to confer cross-protection for the prevention of future epidemics.
      Altogether, Bac-P1-C3CD and the bioprocess render mass production more
      economical, obviate the need for cell lysis and hold promise for future
      industrial vaccine production.

PMID- 20797456
TI  - Proctalgia as a late complication of stapled hemorrhoidectomy. Report of our case
      series.
AB  - INTRODUCTION: Incidence and etiology of persistent pain after stapled
      hemorrhoidectomy remain uncertain. Characteristics, clinical course and
      management of this complication have not yet been assessed. Purpose of this essay
      is to describe our experience with persistent pain in our series of patients with
      this technique. METHODS: This retrospective study evaluated 126 cases of stapled
      hemorrhoidectomy treated from 2006 to 2009. We gathered information on each
      patient regarding type of prolapsed hemorrhoids, number of haemostatic suture
      placed, histology of each doughnut and post operative complications. A close
      follow up was done in those patients complaining about pain. RESULTS: Early and
      late complications occurred in 11.9% and 16.7% of patients respectively. At two
      weeks from surgery 18 patients (14.3%) were complaining of persistent pain. The
      average number of haemostatic sutured placed in this group and in all series is
      4.5 and 2.5 respectively. Eight patients (6.34%), 3 (2.4%) and 2 (1.6%) patients
      were still complaining of persistent pain at 1 month, 4 months and 6 months of
      follow up, respectively. In these patients, endoanal manometry was normal at 4
      months from surgery, while endoanal ultrasound showed retained staples in 3 of
      them. At 7 months from surgery a staples removal was performed in 2 patients that
      were still complaining of pain. CONCLUSIONS: Incidence of pain at 2 weeks after
      surgery resulted in 14.3% of patients. In most patients its etiology remains
      unclear but we reckon it might be related to the high number of haemostatic
      sutures placed. Staples removal resulted successfully.

PMID- 20797457
TI  - Pathogen proteomes during infection: A basis for infection research and novel
      control strategies.
AB  - Infectious diseases cause tremendous mortality and morbidity worldwide. Rising
      antimicrobial resistance and the lack of new drugs cause an increasingly alarming
      crisis in infectious disease control. New system-level approaches are likely to
      help understand complex host/pathogen interactions as a basis for rational
      development of novel antibiotics and vaccines. Proteome analysis of pathogens in
      infected tissues comprehensively reveals functionally relevant pathogen
      activities during infection. It also highlights potential targets for
      antimicrobial chemotherapy as well as promising antigens for vaccination.
      Integration of these data with complementary large-scale data helps to further
      prioritize candidates for in-depth experimental analysis. Here, I discuss some of
      these approaches with a special emphasis on the model pathogen Salmonella.

PMID- 20797458
TI  - Advances in shotgun proteomics and the analysis of membrane proteomes.
AB  - The emergence of shotgun proteomics has facilitated the numerous biological
      discoveries made by proteomic studies. However, comprehensive proteomic analysis
      remains challenging and shotgun proteomics is a continually changing field. This
      review details the recent developments in shotgun proteomics and describes
      emerging technologies that will influence shotgun proteomics going forward. In
      addition, proteomic studies of integral membrane proteins remain challenging due
      to the hydrophobic nature in integral membrane proteins and their general low
      abundance levels. However, there have been many strategies developed for
      enriching, isolating and separating membrane proteins for proteomic analysis that
      have moved this field forward. In summary, while shotgun proteomics is a widely
      used and mature technology, the continued pace of improvements in mass
      spectrometry and proteomic technology and methods indicate that future studies
      will have an even greater impact on biological discovery.

PMID- 20797459
TI  - Sudden death risk in type 2 diabetic patients post-myocardial infarction: a
      "sweet" opportunity?

PMID- 20797460
TI  - Combined exercise training reduces IFN-gamma and IL-17 levels in the plasma and
      the supernatant of peripheral blood mononuclear cells in women with multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder in which
      lymphocytic infiltration mediated mainly by pro-inflammatory cytokines. In this
      study, we examined the effect of combined exercise training on the levels of IFN
      gamma, IL-4 and IL-17 in the plasma and the supernatant of peripheral blood
      lymphocytes in women with multiple sclerosis. Expanded Disability Status Scale
      (EDSS), VO(2)max, muscle strength, and balance tests were obtained at baseline
      and post-treatment follow-up. Combined exercises training was designed for 24
      sessions during 8 weeks. Each session was started with 5 min warm-up and was
      followed by 10 min stretch training, 20 min aerobic exercises and 20 min
      resistance-endurance training. The disability score was significantly decreased
      in test MS subjects after 8 weeks combined exercise training. Muscle strength and
      balance were increased significantly after the training program in test group. In
      this study, plasma, and peripheral blood mononuclear cell (PBMC) IL-17 and IFN
      gamma production was significantly decreased after 8 weeks combined training. Our
      findings suggest that combined training has useful anti-inflammatory effects by
      decrease in PBMC and plasma IL-17 production.

PMID- 20797461
TI  - Studies in genetically modified mice suggest novel mechanisms of mood regulation.

PMID- 20797462
TI  - Phalangeal fractures of the hand.
AB  - The present review systematically describes common fractures of the phalanges
      with reference to the anatomy and the pertinent radiological classifications; in
      particular, the role of radiology in indicating prognosis, guiding treatment, and
      revealing subtle injuries, which may cause permanent loss of function.

PMID- 20797463
TI  - Hilar cholangiocarcinoma: MR correlation with surgical and histological findings.
AB  - AIM: To evaluate magnetic resonance cholangiography (MRC) with high-resolution
      dynamic gadolinium-enhanced magnetic resonance imaging (MRI) in determining the
      imaging features of hilar cholangiocarcinoma that relate to tumour extent and
      influence resectability. MATERIALS AND METHODS: Twenty-six patients that
      underwent resection were reviewed. Tumour location and extent, lobar atrophy, the
      degree of portal vein and hepatic artery involvement were recorded. The findings
      were correlated with surgical and histopathological findings. RESULTS: Biliary
      assessment was concordant in 14 and discordant in eight of 14 stented and four of
      12 non-stented patients. In 63/82 veins and 43/74 arteries results were fully
      concordant. The mean sensitivity, specificity, positive and negative predictive
      values (PPV, NPV) in predicting involvement of the main portal vein (MPV) at
      surgery were 83.3, 100, 100, and 92.5%; of the left main branch of the portal
      vein (LPV) were 100, 91.6, 93.3, and 100%; and of the right branch of the portal
      vein (RPV) were 87.5, 100, 100, and 87.5%. The sensitivity, specificity, PPV and
      NPV of MRI in determining histological involvement of the MPV was 75, 90.9, 60,
      and 92.5%; 100, 73.3, 73, and 100% for the LPV, and 100, 66.6, 42.8, and 100% for
      the RPV, respectively. CONCLUSION: MRC with high-resolution dynamic gadolinium
      enhanced MRI is effective in determining tumour extent and vascular involvement,
      but prior stenting may lead to overestimation.

PMID- 20797464
TI  - MRI findings in the painful hemiplegic shoulder.
AB  - AIM: To evaluate the magnetic resonance imaging (MRI) findings in painful
      hemiplegic shoulder (PHS) in hemiplegic post-stroke patients. MATERIALS AND
      METHODS: Patients with hemiplegia following their first cerebrovascular accident
      who were admitted to the Sarah Network of Hospitals for Rehabilitation were
      studied. Forty-five patients with pain in the hemiplegic shoulder and 23 post
      stroke patients without shoulder pain were investigated. MRI and radiographic
      findings of the hemiplegic and contralateral asymptomatic shoulders were
      evaluated. RESULTS: Some MRI findings were more frequent in PHS group, including
      synovial capsule thickening, synovial capsule enhancement, and enhancement in the
      rotator cuff interval. CONCLUSIONS: Adhesive capsulitis was found to be a
      possible cause of PHS.

PMID- 20797465
TI  - Ketamine-associated lower urinary tract destruction: a new radiological
      challenge.
AB  - AIM: Ketamine is a short-acting dissociative anaesthetic whose hallucinogenic
      side effects have led to an increase in its illicit use amongst club and party
      goers. There is a general misconception amongst users that it is a safe drug with
      few long term side effects, however ketamine abuse is associated with severe
      urinary tract dysfunction. Presenting symptoms include urinary frequency,
      nocturia, dysuria, haematuria and incontinence. MATERIALS AND METHODS: We
      describe the radiological findings found in a series of 23 patients, all with a
      history of ketamine abuse, who presented with severe lower urinary tract symptoms
      (LUTS). Imaging techniques used included ultrasonography (US), intravenous
      urography (IVU), and computed tomography (CT). These examinations were reviewed
      to identify common imaging findings. All patients with positive imaging findings
      had also undergone cystoscopy and bladder wall biopsies, which confirmed the
      diagnosis. The patients in this series have consented to the use of their data in
      the ongoing research into ketamine-induced bladder pathology. RESULTS: Ultrasound
      demonstrated small bladder volume and wall thickening. CT revealed marked,
      generalized bladder wall thickening, mucosal enhancement, and perivesical
      inflammation. Ureteric wall thickening and enhancement were also observed. In
      advanced cases ureteric narrowing and strictures were identified using both CT
      and IVU. Correlation of clinical history, radiological and pathological findings
      was performed to confirm the diagnosis. CONCLUSION: This case series illustrates
      the harmful effects of ketamine on the urinary tract and the associated
      radiological findings. Delayed diagnosis can result in irreversible renal tract
      damage requiring surgical intervention. It is important that radiologists are
      aware of this emerging clinical entity as early diagnosis and treatment are
      essential for successful management.

PMID- 20797466
TI  - CT and MRI findings of cirrhosis-related benign nodules with ischaemia or
      infarction after variceal bleeding.
AB  - AIM: To present computed tomography (CT) and magnetic resonance imaging (MRI)
      findings of cirrhosis-related benign nodules with ischaemia or infarction.
      MATERIALS AND METHODS: Sixteen consecutive patients (14 men and two women) who
      had been diagnosed with cirrhosis-related benign nodules with ischaemia or
      infarction after variceal bleeding based on the results of dynamic CT (n=15) and
      MRI (n=8) were included in this study. Five patients had histopathological
      confirmation via liver transplantation (n=2) and percutaneous biopsy (n=3).
      Images were analyzed for the enhancement pattern, signal intensities, location,
      and configuration of the lesions. RESULTS: Most of the lesions were depicted as
      multifocal discrete or clustered nodules with some irregular patchy areas (size
      range 3-28 mm). They were predominantly found in subcapsular area or caudate
      lobe. Most nodular lesions were seen as hypoattenuating (hypointense) nodules
      with rim enhancement during dynamic CT or MRI. On T2-weighted images, nodular
      lesions were predominantly seen as target appearing hyperintense nodules. On
      follow-up images (range 2-24 months), most of the lesions disappeared or
      decreased in size. CONCLUSION: CT and MRI can be used to demonstrate
      characteristic findings of cirrhosis-related benign nodules with ischaemia or
      infarction. Rapid resolution of the nodules at follow-up imaging can also be
      helpful for diagnosing these lesions.

PMID- 20797467
TI  - Prospective ECG triggering versus low-dose retrospective ECG-gated 128-channel CT
      coronary angiography: comparison of image quality and radiation dose.
AB  - AIM: To evaluate image quality and radiation dose for 128-detector prospective
      electrocardiogram (ECG)-gated computed tomography coronary angiography (CTCA)
      compared with a low-dose retrospective ECG-gated imaging protocol. MATERIALS AND
      METHODS: Thirty-one and 47 patients suspected of having coronary artery disease
      were enrolled into groups examined using prospective and low-dose retrospective
      ECG-gated CT protocols respectively. All examinations were performed on a 128
      detector CT system (Definition AS, Siemens Healthcare, Forchheim, Germany).
      Prospective CTCA was performed using following parameters: tube voltage 100 kV;
      tube current 205 mAs; centre of acquisition window 70% of the RR interval. The
      tube current for low-dose retrospective ECG-gated CTCA was full dose during 40
      70% of the RR interval and partial dose for the rest of RR interval. The pitch
      varied between 0.2 and 0.5 depending on heart rate and patient size. Image
      quality of coronary arteries was evaluated using a four-point grading scale. The
      signal-to-noise ratios (SNRs) of enhanced arteries and myocardium were also
      measured, corresponding contrast-to-noise ratios (CNRs) were calculated, and the
      radiation doses received were recorded. RESULTS: There was a significant
      difference in the image quality scores between the retrospective and prospective
      gating protocols (Chi-square=15.331, p=0.009). There was no significant
      difference between the SNRs of the contrasted artery and myocardium in these two
      groups, but the CNRs were increased in the prospective group. The mean radiation
      dose of prospective gating group was 2.71+/-0.67 mSv (range, 1.67-3.59 mSv),
      which was significantly lower than that of the retrospective group (p<0.001).
      CONCLUSION: Prospective CT angiography can achieve lower radiation dose than that
      of low-dose retrospective CT angiography, with preserved image quality.

PMID- 20797468
TI  - Detection of coronary artery anomalies by dual-source CT coronary angiography.
AB  - AIM: To retrospectively evaluate the clinical value of dual-source computed
      tomography (DSCT) coronary angiography in the diagnosis of coronary artery
      anomalies. MATERIALS AND METHODS: A large cohort of 3625 consecutive patients,
      who underwent DSCT coronary angiography in our institute, was reviewed for
      coronary artery anomalies. All images were evaluated by two experienced readers
      using axial source images, multi-planar reformations (MPR), maximum intensity
      projections (MIP) and volume rendering (VR). Coronary artery anomalies were found
      in 36 patients (male 20, female 16, mean age 48 years, range 15-76 years). Of the
      36 patients, 19 patients also underwent conventional coronary angiography (CCA).
      RESULTS: The incidence of coronary artery anomalies was 0.99% (36/3625). Six
      different types of coronary artery anomalies were diagnosed by DSCT coronary
      angiography: (1) 11 anomalies of the right coronary artery; (2) five anomalies of
      the left coronary artery; (3) 10 anomalies of the left circumflex artery; (4) two
      single coronary artery; (5) one anomalous pulmonary origin of the coronary
      artery; (6) seven coronary artery fistula. Evaluation of the CCA resulted in a
      precise diagnosis in 53% (10/19) patients. CONCLUSION: DSCT coronary angiography
      is a good diagnostic tool to examine coronary artery anomalies.

PMID- 20797469
TI  - The idiopathic interstitial pneumonias: understanding key radiological features.
AB  - Many radiologists find it challenging to distinguish between the different
      interstitial idiopathic pneumonias (IIPs). The British Thoracic Society
      guidelines on interstitial lung disease (2008) recommend the formation of
      multidisciplinary meetings, with diagnoses made by combined radiological,
      pathological, and clinical findings. This review focuses on understanding typical
      and atypical radiological features on high-resolution computed tomography between
      the different IIPs, to help the radiologist determine when a confident diagnosis
      can be made and how to deal with uncertainty.

PMID- 20797470
TI  - Imaging of skull-base cephalocoeles and cerebrospinal fluid leaks.
AB  - Skull-base cephalocoeles and cerebrospinal fluid (CSF) leaks may be congenital,
      spontaneous, or secondary. A classification of congenital lesions is formulated
      and the imaging features are illustrated. The concept of spontaneous skull-base
      CSF leaks and the significance of aberrant arachnoid granulations in imaging
      these patients are explored. The majority of secondary lesions relate to trauma;
      however, other potential causes of secondary skull-base cephalocoeles and CSF
      leaks are discussed. Imaging evaluation in these clinical scenarios may be
      complex and the role of each imaging method is reviewed.

PMID- 20797471
TI  - Incidental bony pathology when reporting trauma orthopantomograms.
AB  - Radiologists frequently report orthopantomograms (OPTs) and other views of the
      mandible, most often in patients who have suffered facial trauma. These
      examinations may reveal incidental pathology. It is important that radiologists
      are aware of the radiological appearances and the clinical significance of these
      lesions. In this review we will present examples of the more common odontogenic
      lesions including: radicular cyst, odontogenic keratocyst, dentigerous cyst,
      ameloblastoma, and also examples of non-odontogenic pathology: bisphosphonate
      related osteonecrosis of the jaw (BRONJ) and chronic osteomyelitis. Although some
      of the lesions will require computed tomography (CT) or magnetic resonance
      imaging (MRI) for further lesion characterization and evaluation of the
      surrounding tissues, we are going to focus on the plain film appearances. We will
      also briefly discuss the pathogenesis, epidemiology, and treatment of these
      lesions.

PMID- 20797472
TI  - Unusual appearance of bowel anastomosis staple line mimicking a retained surgical
      swab.

PMID- 20797473
TI  - Re: Measurement of defect angle in superior semicircular canal dehiscence.

PMID- 20797475
TI  - Flaxseed lignan lowers blood cholesterol and decreases liver disease risk factors
      in moderately hypercholesterolemic men.
AB  - The effects of flaxseed lignan (secoisolariciresinol diglucoside [SDG]) intake on
      hypercholesterolemia and liver disease risk factors in moderately
      hypercholesterolemic men were investigated. In a previous study, we reported that
      SDG attenuates high-fat, diet-induced hypercholesterolemia in mice. Here, we
      report a double-blinded, randomized, and placebo-controlled study in moderately
      hypercholesterolemic men in which we investigated the hypothesis that oral
      administration of SDG (20 or 100 mg) would decrease the level of blood
      cholesterol and liver disease risk factors induced by hypercholesterolemia in
      humans. Thirty men with total cholesterol levels of 4.65 to 6.21 mmol/L (180-240
      mg/dL) were randomly assigned to 3 groups; 2 groups received flaxseed lignan
      capsules (SDG, 20 or 100 mg/d) and the other received placebo capsules for 12
      weeks. We found that, compared to the subjects who received placebo, those who
      received 100 mg of SDG exhibited a significant reduction in the ratio of low
      density lipoprotein/high-density lipoprotein cholesterol at baseline (P < .05)
      and at week 12 (P < .05). In addition, in SDG-treated subjects, we also observed
      a significant percentage decrease in the levels of glutamic pyruvic transaminase
      and gamma-glutamyl transpeptidase relative to the levels at baseline (P < .01)
      and a significant percentage decrease in the level of gamma-glutamyl
      transpeptidase relative to the placebo-treated group (P < .05). These results
      suggest that daily administration of 100 mg SDG can be effective at reducing
      blood level of cholesterol and hepatic diseases risk in moderately
      hypercholesterolemic men.

PMID- 20797476
TI  - Inclusion of Atlantic salmon in the Chinese diet reduces cardiovascular disease
      risk markers in dyslipidemic adult men.
AB  - Although the beneficial effects of n-3 fatty acids on several physiologic
      functions have been widely reported, information about the effects of oily fish
      in the Asian diet on cardiovascular disease (CVD) risk is diminutive. We
      hypothesize that daily inclusion of oily fish for 8 weeks in the Chinese diet
      will elevate serum eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)
      levels and reduce CVD risk markers in dyslipidemic adult men, comparable with the
      effects generally observed by inclusion of oily fish in the Western diet. In this
      8-week randomized, parallel-arm, food-based intervention study, lunches were
      prepared with 500 g pork/chicken/beef, typically consumed fish (hairtail and
      freshwater carp), or oily fish (salmon). Male subjects aged between 35 and 70
      years with hyperlipidemia were randomly assigned to eat lunches with
      pork/chicken/beef (n = 30 subjects at 8 weeks), freshwater fish (n = 30), or oily
      fish (n = 32). Circulating markers were measured at baseline and at 8 weeks. In
      the oily fish diet, dietary EPA and DHA levels were significantly increased as
      compared with other diets; and the n-6:n-3 polyunsaturated fatty acid ratio was
      decreased (P < .05). Thus, the oily fish diet significantly elevated serum EPA
      and DHA concentrations (P < .01) and lowered serum n-6:n-3 ratio at 8 weeks (P <
      .05). Furthermore, oily fish intake significantly reduced serum levels of
      triglycerides (P < .05) and interleukin-6 (P < .01) and increased levels of high
      density lipoprotein cholesterol (P < .01). In conclusion, daily inclusion of oily
      fish as part of the Chinese diet for 8 weeks is sufficient to significantly
      increase the serum content of long-chain n-3 polyunsaturated fatty acids and
      reduce levels of CVD risk markers in dyslipidemic adult men.

PMID- 20797477
TI  - Hypoxanthine levels in human urine serve as a screening indicator for the plasma
      total cholesterol and low-density lipoprotein modulation activities of fermented
      red pepper paste.
AB  - Fermented red pepper paste (FRPP) is one of the most well-known traditional foods
      in Korea. The effects of FRPP in experimental animals and adipocytes have been
      previously reported. However, the biochemical effects have not yet been validated
      in humans with various genetic backgrounds and environmental factors. In this
      study, 28 female volunteers (body mass index, more than 23 kg/m(2)) aged 19 to 60
      years were treated with either FRPP or a placebo for 12 weeks. Marked cholesterol
      modulation was observed in the FRPP-treated group compared with the placebo
      group. Although the baseline (pretreatment) total cholesterol and low-density
      lipoprotein levels and body mass index of the volunteers did not differ
      significantly between the placebo- and FRPP-treated groups, FRPP caused a
      modulation of cholesterol levels not seen in the placebo group, causing either no
      variation or a decrease in low-density lipoprotein and total cholesterol levels.
      Thus, urinary metabolomic profiling of pretreatment samples was carried out in
      these 2 FRPP-treated groups using (1)H-nuclear magnetic resonance-based
      metabolomic techniques. These 2 groups, with their opposing cholesterol
      modulation tendencies, could be clearly differentiated by orthogonal projections
      to latent structures-discriminant analysis-derived score plots. In addition,
      their levels of hypoxanthine differed markedly. We propose that urinary
      hypoxanthine levels can be used as a screening biomarker to predict the efficacy
      of the cholesterol-modulating activity of FRPP in human subjects.

PMID- 20797478
TI  - Strawberries decrease atherosclerotic markers in subjects with metabolic
      syndrome.
AB  - Strawberries have been reported to be potent antioxidants and reduce
      cardiovascular risk factors, such as elevated blood pressure, hyperglycemia,
      dyslipidemia, and inflammation in limited studies. We hypothesized that freeze
      dried strawberry supplementation will improve blood pressure, impaired glucose,
      dyslipidemia, or circulating adhesion molecules in obese subjects with metabolic
      syndrome, thereby lowering cardiovascular risk factors in these subjects. Twenty
      seven subjects with metabolic syndrome (2 males and 25 females; body mass index,
      37.5 +/- 2.15 kg/m(2); age, 47.0 +/- 3.0 years [means +/- SE]) consumed 4 cups of
      freeze-dried strawberry beverage (50 g freeze-dried strawberries approximately 3
      cups fresh strawberries) or equivalent amounts of fluids (controls, 4 cups of
      water) daily for 8 weeks in a randomized controlled trial. Anthropometrics and
      blood pressure measurements, assessment of dietary intakes, and fasting blood
      draws were conducted at screen and 8 weeks of the study. Strawberry
      supplementation significantly decreased total and low-density lipoprotein
      cholesterol (5.8 +/- 0.2 to 5.2 +/- 0.2 mmol/L and 3.5 +/- 0.2 to 3.1 +/- 0.1
      mmol/L, respectively [means +/- SE], P < .05) and small low-density lipoprotein
      particles using nuclear magnetic resonance-determined lipoprotein subclass
      profile vs controls at 8 weeks (794.6 +/- 94.0 to 681.8 +/- 86.0 nmol/L [means +/
      SE], P < .05). Strawberry supplementation further decreased circulating levels
      of vascular cell adhesion molecule-1 vs controls at 8 weeks (272.7 +/- 17.4 to
      223.0 +/- 14.0 ng/mL [means +/- SE], P < .05). Serum glucose, triglycerides, high
      density lipoprotein cholesterol, blood pressure, and waist circumference were not
      affected. Thus, short-term freeze-dried strawberry supplementation improved
      selected atherosclerotic risk factors, including dyslipidemia and circulating
      adhesion molecules in subjects with metabolic syndrome, and these results need
      confirmation in future trials.

PMID- 20797479
TI  - Association between household income and overweight of Korean and American
      children: trends and differences.
AB  - The prevalence of overweight in children has been dramatically increasing
      worldwide, and socioeconomic status is an important risk factor. The purpose of
      this study was to examine the hypothesis that household income is negatively
      associated with overweight in Korean and American girls and boys. In the study,
      2117 children 7 to 12 years of age from the Korean National Health and Nutrition
      Examination Survey between 2001 and 2007 and 3016 children from the US National
      Health and Nutrition Examination Survey between 2001 and 2006 were included.
      Overweight is defined as the sex- and age-specific body mass index cutoffs
      recommended by the International Obesity Task Force. Lower household income
      significantly increased the risk for overweight in Korean boys, irrespective of
      adjustments. The negative association between household income and overweight of
      American boys disappeared after adjusting for the frequency of dining out and TV
      viewing time. There was no significant association between household income and
      overweight of Korean and American girls. As household income increased, the
      intake of energy from protein was increased, but energy from carbohydrates was
      decreased in Korean boys. On the other hand, as household income increased,
      energy intake from carbohydrates was increased and energy intake from proteins
      decreased in American boys. In conclusion, positive association between household
      income and overweight was found in Korean boys, but not in Korean girls and
      American boys and girls. Effects solely targeting reduction in income disparities
      cannot effectively reduce sex disparities in overweight of children.

PMID- 20797480
TI  - Decisional balance for health and weight is associated with whole-fruit intake in
      low-income young adults.
AB  - Bone health, decreased risk of certain cancers, heart disease, and stroke has
      been associated with the consumption of fruits. These and other health benefits,
      such as feeling better and weight loss, have been identified as intrinsic
      motivators for consumers to increase their consumption of fruits. Thus, if
      individuals believe more could be gained than lost (decisional balance) by
      increasing their fruit intake, it is likely that they will consume more. However,
      despite fruits' positive effect on health, young adults and individuals with low
      incomes, limited education, or low self-efficacy consume insufficient amounts. To
      determine variables associated with increased fruit consumption, we hypothesized
      that decisional balance pros for health and weight would be associated with
      increased fruit consumption in young adults with low incomes. We surveyed 235
      respondents between the ages of 18 and 24 years, with an annual income less than
      $25,000. Multiple regression analysis measured the impact of the independent
      variables' (i.e., age, weight satisfaction, income, education, self-efficacy, and
      pros and cons decisional balance) association with fruit consumption. The
      decisional balance pros was significantly (F = 2.189, P = .036) associated with
      overall fruit consumption. Respondents consumed 1.94 +/- 1.64 cups of fruit
      daily, with fruit juices consumed in greater amounts than any other form of
      fruit. Decisional balance questions relating to health (P < .05) and weight (P <
      .01) were significantly related to increased whole fruit intake. Results of this
      study suggest that decisional balance pros for health and weight can be used to
      predict whole-fruit consumption in low-income young adults.

PMID- 20797481
TI  - A high-fat diet inhibits the progression of diabetes mellitus in type 2 diabetic
      rats.
AB  - It is well known that rats and mice, when fed a high-fat diet, develop obesity
      associated with abnormal glycolipid metabolism. In this study, we investigated
      the effects of a high-fat diet on a diabetic rat model, Spontaneously Diabetic
      Torii (SDT), which develops diabetes due to decreased insulin production and
      secretion with age. We hypothesized that a high-fat diet would accelerate the
      induction of diabetes in this model. The SDT rats were divided into 2 groups,
      which were fed a high-fat diet or standard diet for 16 weeks. The group fed a
      high-fat diet developed obesity, hyperinsulinemia, and hyperlipidemia until 16
      weeks of age. Before 16 weeks of age, hyperglycemia accompanied by
      hypoinsulinemia developed in the group on a standard diet, but serum glucose
      levels were comparable in both groups. After 16 weeks of age, the group on a
      standard diet showed an increase in serum glucose levels and a decrease in serum
      insulin levels. Unexpectedly, in the group on the high-fat diet, we observed a
      suppressed of the progression of hyperglycemia/hypoinsulinemia. Histopathological
      observation revealed more pancreatic beta cells in the group on the high-fat
      diet. This study suggests that feeding SDT rats a high-fat diet induces obesity,
      hyperinsulinemia, and hyperlipidemia, but not hyperglycemia, until 16 weeks of
      age. Thereafter, age-dependent progress of hyperglycemia and hypoinsulinemia was
      delayed by a high-fat diet. The hyperfunction of pancreatic beta cells induced by
      a high-fat diet before the onset of hyperglycemia appears to suppress development
      of hyperglycemia/hypoinsulinemia.

PMID- 20797483
TI  - Red yeast rice stimulates osteoblast proliferation and increases alkaline
      phosphatase activity in MC3T3-E1 cells.
AB  - Red yeast (Monascus purpureus) is used as a traditional hypocholesterolemic
      dietary food component in Asia due to its bioactive component, lovastatin.
      Recently, new evidence suggesting that the statins in red yeast enhance bone
      formation has been reported, but more research is still needed in order to
      support these claims of osteogenic effects. Therefore, in this study, we
      hypothesized that red yeast rice (in which red yeast is fermented) can improve
      osteogenic function through osteoblast cell proliferation and differentiation. We
      studied the effect of methanol extract of red yeast rice powder (RYRP) on
      osteoblast proliferation and differentiation by measuring mitochondrial enzyme
      activity and bone marker alkaline phosphatase (ALP) activity, respectively.
      Osteoblast-like MC3T3-E1 cells were cultured in various concentrations of RYRP
      methanol extract (0.001-1 mg/mL) during the osteoblast differentiation period (1,
      5, 10, and 15 days). As measured by 3-[4,5-dimethylthiazol-2-y]-2,5
      diphenyltetrazolium bromide assay, RYRP extracts stimulated cell proliferation
      during a 24-hour period, compared to cooked white rice powder extract. The most
      pronounced effect was observed at the concentration range between 0.075 and 0.1
      mg/mL. This RYRP stimulatory effect for cell proliferation was observed during
      the whole osteogenic period. Cellular (synthesized) ALP activity was increased at
      a RYRP extract concentration of 0.075 mg/mL during 15 days of culture, but the
      medium (secreted) ALP activity did not show any significant change. This cellular
      ALP activity stimulation by RYRP extract was confirmed by the staining of ALP
      activity on cell matrix layers for matrix calcification. The results imply that
      RYRP extract may increase osteogenic effect by stimulating cell proliferation and
      ALP activity in osteoblastic cells.

PMID- 20797484
TI  - Serosurvey for Trichinella in polar bears (Ursus maritimus) from Svalbard and the
      Barents Sea.
AB  - Blood samples of live-caught polar bears (Ursus maritimus) from Svalbard
      collected 1991-2000 (Period 1) and 2006-2008 (Period 2) and from the pack ice of
      the Barents Sea collected in Period 1, were assayed for antibodies against
      Trichinella spp. by ELISA. Of 54 cubs-of-the-year included in the Period 1
      sample, 53 were seronegative, indicating that exposure to Trichinella infected
      meat is uncommon during the first months of life for polar bears in the Svalbard
      region. Of 30 mother-offspring pairs, 18 mothers were seropositive with
      seronegative offspring (n=27), suggesting (1) that maternal antibodies had
      dropped to levels below detection limit by the time of capture in April
      (offspring approximately 4 months old), and (2) supporting experimental studies
      in other animal models showing that vertical transmission of Trichinella spp. is
      uncommon. Bear 1 year and older had higher prevalence in Svalbard (78%) than in
      the Barents Sea (51%). There was no temporal change in prevalence for bears from
      Svalbard during the time between the two periods. The prevalence increased with
      age in both sexes. A positive correlation was found between anti-Toxoplasma
      gondii and anti-Trichinella spp. antibodies.

PMID- 20797482
TI  - Dietary intake of S-(alpha-carboxybutyl)-DL-homocysteine induces
      hyperhomocysteinemia in rats.
AB  - Betaine homocysteine S-methyltransferase (BHMT) catalyzes the transfer of a
      methyl group from betaine to homocysteine (Hcy), forming dimethylglycine and
      methionine. We previously showed that inhibiting BHMT in mice by intraperitoneal
      injection of S-(alpha-carboxybutyl)-DL-homocysteine (CBHcy) results in
      hyperhomocysteinemia. In the present study, CBHcy was fed to rats to determine
      whether it could be absorbed and cause hyperhomocysteinemia as observed in the
      intraperitoneal administration of the compound in mice. We hypothesized that
      dietary administered CBHcy will be absorbed and will result in the inhibition of
      BHMT and cause hyperhomocysteinemia. Rats were meal-fed every 8 hours an L-amino
      acid-defined diet either containing or devoid of CBHcy (5 mg per meal) for 3
      days. The treatment decreased liver BHMT activity by 90% and had no effect on
      methionine synthase, methylenetetrahydrofolate reductase,
      phosphatidylethanolamine N-methyltransferase, and CTP:phosphocholine
      cytidylyltransferase activities. In contrast, cystathionine beta-synthase
      activity and immunodetectable protein decreased (56% and 26%, respectively) and
      glycine N-methyltransferase activity increased (52%) in CBHcy-treated rats. Liver
      S-adenosylmethionine levels decreased by 25% in CBHcy-treated rats, and S
      adenosylhomocysteine levels did not change. Furthermore, plasma choline decreased
      (22%) and plasma betaine increased (15-fold) in CBHcy-treated rats. The treatment
      had no effect on global DNA and CpG island methylation, liver histology, and
      plasma markers of liver damage. We conclude that CBHcy-mediated BHMT inhibition
      causes an elevation in total plasma Hcy that is not normalized by the folate
      dependent conversion of Hcy to methionine. Furthermore, metabolic changes caused
      by BHMT inhibition affect cystathionine beta-synthase and glycine N
      methyltransferase activities, which further deteriorate plasma Hcy levels.

PMID- 20797485
TI  - Giant cell myocarditis associated with Coxsackievirus infection.

PMID- 20797486
TI  - Left ventricular endocardial stimulation for severe heart failure.
AB  - Biventricular resynchronization, a therapy recommended for patients presenting
      with left ventricular (LV) dysfunction and ventricular dyssynchrony, requires the
      implantation of an LV lead, usually placed in a lateral or posterolateral
      tributary of the coronary sinus. Despite important progress made in the
      development of dedicated instrumentation, the procedure remains sometimes
      challenging and unsuccessful in a minority of patients. In the rare instances of
      unsuccessful transvenous implantations occurring in the presence of major
      surgical contraindications, a few operators have implanted the LV lead
      transseptally, an approach limited by technical difficulties and by the
      thromboembolic risk associated with the presence of a lead inside the LV cavity.
      The interest in this approach was recently renewed by 2 studies in an animal
      model and in humans, respectively, which both found a distinctly superior
      hemodynamic performance associated with endocardial compared with epicardial
      stimulation. This review discusses the advantages and disadvantages of LV
      endocardial stimulation, examines the various techniques of LV endocardial
      stimulation, and projects their future applications in light of these highly
      promising recent results. The implementation of endocardial stimulation will
      ultimately depend on: 1) the development of safe, effective, and durable
      instrumentation, and reliable and reproducible intraprocedural methods to
      identify the optimal site of stimulation; and 2) the completion of controlled
      trials confirming the superiority of this technique compared with standard
      cardiac resynchronization therapy.

PMID- 20797487
TI  - Critical appraisal of the use of cardiac resynchronization therapy beyond current
      guidelines.
AB  - Cardiac resynchronization therapy (CRT) is an effective treatment for patients
      with drug-refractory, chronic heart failure. Multiple single-center and
      multicenter studies have shown significant reductions in left ventricular (LV)
      volumes and an increase in LV systolic function. More importantly, CRT reduces
      mortality and morbidity during long-term follow-up. Current guidelines consider
      CRT as a Class I indication for heart failure patients in New York Heart
      Association (NYHA) functional class III to IV with depressed LV ejection fraction
      <or=35% and a wide QRS complex (>or=120 ms). However, the benefits of this
      therapy could possibly be extended to selected subgroups of patients who do not
      fulfill these criteria. These subgroups include patients with mildly symptomatic
      heart failure and patients with a narrow QRS complex (<120 ms). Results from
      recent multicenter controlled clinical trials including heart failure patients in
      NYHA functional class I to II or with a narrow QRS complex are equivocal.
      Although expanding CRT to patients with a narrow QRS complex seems currently not
      likely, the benefits of CRT in mildly symptomatic patients are more evident.
      Perhaps attenuation of disease progression will prove to be a successful new
      treatment strategy in heart failure patients in the future. In addition,
      multimodality cardiac imaging will allow optimizing responder rate in patients
      undergoing CRT according to current guidelines.

PMID- 20797488
TI  - Extending the use of cardiac resynchronization therapy: do we need a new
      algorithm?

PMID- 20797489
TI  - Prevalence and predictors of off-label use of cardiac resynchronization therapy
      in patients enrolled in the National Cardiovascular Data Registry Implantable
      Cardiac-Defibrillator Registry.
AB  - OBJECTIVES: The purpose of the study was to define the extent and nature of
      cardiac resynchronization therapy (CRT) device usage outside consensus guidelines
      using national data. BACKGROUND: Recent literature has shown that the application
      of CRT in clinical practice frequently does not adhere to evidence-based
      consensus guidelines. Factors underlying these practices have not been fully
      explored. METHODS: From the National Cardiovascular Data Registry's Implantable
      Cardiac-Defibrillator Registry, we defined a cohort of 45,392 cardiac
      resynchronization therapy-defibrillator (CRT-D) implants between January 2006 and
      June 2008 with a primary prevention indication. We defined "off-label" implants
      as those in which the ejection fraction was >35%, the New York Heart Association
      functional class was below III, or the QRS interval duration was <120 ms in the
      absence of a documented need for ventricular pacing. The relationships between
      patient, implanting physician, and hospital characteristics with off-label use
      were explored with multivariable hierarchical logistic regression models.
      RESULTS: Overall, 23.7% of devices were placed without meeting all 3 implant
      criteria, most often due to New York Heart Association functional class below III
      (13.1% of implants) or QRS interval duration <120 ms (12.0%). Atrial
      fibrillation/flutter, previous percutaneous coronary intervention, and the
      performance of an electrophysiology study before implant were independently
      associated with increased odds of off-label use, whereas diabetes mellitus,
      increasing age, and female sex were associated with decreased odds. Physician
      training and insurance payer were weakly associated with the likelihood of off
      label use. CONCLUSIONS: Nearly 1 in 4 patients receiving CRT devices in the study
      time frame did not meet guideline-based indications. Given the evolving evidence
      base supporting the use of CRT, these practices require careful scrutiny.

PMID- 20797490
TI  - Optimal left ventricular endocardial pacing sites for cardiac resynchronization
      therapy in patients with ischemic cardiomyopathy.
AB  - OBJECTIVES: We sought to investigate the impact of left ventricular (LV) pacing
      site on mechanical response to cardiac resynchronization therapy (CRT) in
      patients with ischemic cardiomyopathy (ICM). BACKGROUND: CRT reduces morbidity
      and mortality in patients with dyssynchronous LV failure; however, variability in
      response, particularly in ICM patients, poses ongoing challenges. Endocardial
      biventricular (BiV) stimulation may provide more flexibility in LV site selection
      and yield more natural transmural activation patterns. Whether this applies to
      ICM and whether optimal LV endocardial pacing locations vary among ICM patients
      remain unknown. METHODS: Peak rate of LV pressure increase (dP/dt(max)) was
      measured at baseline, during VDD pacing at the right ventricular apex, and during
      BiV pacing from the right ventricular apex and 51 +/- 14 different LV endocardial
      sites in patients with ICM (n = 11). Seven patients already had an epicardial LV
      lead (CRT) in place, allowing comparison of epicardial BiV stimulation with that
      using an endocardial site directly transmural to the CRT-coronary sinus lead tip.
      Electroanatomic 3-dimensional maps with color-coded dP/dt(max) response defined
      optimal pacing regions delivering >or=85% of maximal increase in dP/dt(max).
      RESULTS: Endocardial BiV pacing improved dP/dt(max) over right ventricular apex
      pacing in all patients (mean increase 241 +/- 38 mm Hg/s; p < 0.0001). In
      patients with pre-existing CRT leads, LV endocardial versus epicardial pacing at
      transmural sites yielded equivalent dP/dt(max) values. However, dP/dt(max) at the
      best endocardial site exceeded that achieved with the pre-implanted CRT device
      (mean increase 111 +/- 25 mm Hg/s; p = 0.004). An average of approximately 2
      optimal endocardial sites were identified for each patient, located at the
      extreme basal lateral wall (8 of 11 patients) and other regions (9 of 11).
      Standard mid-LV free wall pacing yielded suboptimal LV function in 73% of
      patients. Optimal pacing sites were typically located in LV territories remote
      (9.3 +/- 3.6 cm) from the infarct zone. CONCLUSIONS: CRT delivered at best LV
      endocardial sites is more effective than via pre-implanted coronary sinus lead
      pacing. The location of optimal LV endocardial pacing varies among patients with
      ICM, and individual tailoring may improve CRT efficacy in such patients.

PMID- 20797491
TI  - Optimizing hemodynamics in cardiac resynchronization therapy by left ventricular
      pacing site: you find only what you are looking for.

PMID- 20797492
TI  - Pericardial fat is independently associated with human atrial fibrillation.
AB  - OBJECTIVES: The purpose of this study was to investigate the association between
      atrial fibrillation (AF) and pericardial fat. BACKGROUND: Pericardial fat is
      visceral adipose tissue that possesses inflammatory properties. Inflammation and
      obesity are associated with AF, but the relationship between AF and pericardial
      fat is unknown. METHODS: Pericardial fat volume was measured using computed
      tomography in 273 patients: 76 patients in sinus rhythm, 126 patients with
      paroxysmal AF, and 71 patients with persistent AF. RESULTS: Patients with AF had
      significantly more pericardial fat compared with patients in sinus rhythm (101.6
      +/- 44.1 ml vs. 76.1 +/- 36.3 ml, p < 0.001). Pericardial fat volume was
      significantly larger in paroxysmal AF compared with the sinus rhythm group (93.9
      +/- 39.1 ml vs. 76.1 +/- 36.3 ml, p = 0.02). Persistent AF patients had a
      significantly larger pericardial fat volume compared with paroxysmal AF (115.4 +/
      49.3 ml vs. 93.9 +/- 39.1 ml, p = 0.001). Pericardial fat volume was associated
      with paroxysmal AF (odds ratio: 1.11; 95% confidence interval: 1.01 to 1.23, p =
      0.04) and persistent AF (odds ratio: 1.18, 95% confidence interval: 1.05 to 1.33,
      p = 0.004), and this association was completely independent of age, hypertension,
      sex, left atrial enlargement, valvular heart disease, left ventricular ejection
      fraction, diabetes mellitus, and body mass index. CONCLUSIONS: Pericardial fat
      volume is highly associated with paroxysmal and persistent AF independent of
      traditional risk factors including left atrial enlargement. Whether pericardial
      fat plays a role in the pathogenesis of AF requires future investigation.

PMID- 20797493
TI  - Does elevated C-reactive protein increase atrial fibrillation risk? A Mendelian
      randomization of 47,000 individuals from the general population.
AB  - OBJECTIVES: The purpose of this study was to test whether the association of C
      reactive protein (CRP) with increased risk of atrial fibrillation is a robust and
      perhaps even causal association. BACKGROUND: Elevated levels of CRP previously
      have been associated with increased risk of atrial fibrillation. METHODS: We
      studied 10,276 individuals from the prospective Copenhagen City Heart Study,
      including 771 individuals who had atrial fibrillation during follow-up, and
      another 36,600 persons from the cross-sectional Copenhagen General Population
      Study, including 1,340 cases with atrial fibrillation. Individuals were genotyped
      for 4 CRP gene polymorphisms and had high-sensitivity CRP levels measured.
      RESULTS: A CRP level in the upper versus lower quintile associated with a 2.19
      fold (95% confidence interval [CI]: 1.54- to 3.10-fold) increased risk of atrial
      fibrillation. Risk estimates attenuated slightly after multifactorial adjustment
      to 1.77 (95% CI: 1.22 to 2.55), and after additional adjustment for heart failure
      and plasma fibrinogen level to 1.47 (95% CI: 1.02 to 2.13) and 1.63 (95% CI: 1.21
      to 2.20), respectively. Genotype combinations of the 4 CRP polymorphisms
      associated with up to a 63% increase in plasma CRP levels (p < 0.001), but not
      with increased risk of atrial fibrillation. The estimated causal odds ratio for
      atrial fibrillation by instrumental variable analysis for a doubling in
      genetically elevated CRP levels was lower than the odds ratio for atrial
      fibrillation observed for a doubling in plasma CRP on logistic regression (0.94
      [95% CI: 0.70 to 1.27] vs. 1.36 [95% CI: 1.30 to 1.44]; p < 0.001). CONCLUSIONS:
      Elevated plasma CRP robustly associated with increased risk of atrial
      fibrillation; however, genetically elevated CRP levels did not. This suggests
      that elevated plasma CRP per se does not increase atrial fibrillation risk.

PMID- 20797494
TI  - Atrial tachycardia arising adjacent to noncoronary aortic sinus: distinctive
      atrial activation patterns and anatomic insights.
AB  - OBJECTIVES: We sought to determine whether atrial tachycardia arising adjacent to
      the noncoronary aortic sinus (NCAS-AT) has distinctive atrial activation patterns
      in relation to targeted anatomic imaging. BACKGROUND: The knowledge of atrial
      activation patterns of the NCAS-AT and its anatomic basis is very limited.
      METHODS: Three-dimensional electroanatomic mapping was performed during NCAS-AT
      in 13 patients and during sequentially pacing from the noncoronary aortic sinus
      (NCAS) and the para-Hisian atrial area in 15 reference patients. The spatial
      relationship between the NCAS and the contiguous atria was studied in another 25
      reference patients using computed tomography and in 12 human hearts using gross
      and microscopic anatomic examination. RESULTS: During NCAS-AT, the para-Hisian
      area of the right atrium (RA) and the anteroseptal region of the left atrium were
      activated almost simultaneously. The initial activation area (within first 20 ms
      of atrial depolarization) was relatively wide (9.3 +/- 2.6 cm(2) on the RA map
      and 8.1 +/- 2.1 cm(2) on the left atrium map). In reference patients, NCAS pacing
      reproduced a biatrial activation pattern of NCAS-AT and resulted in a wider
      initial activation area than the para-Hisian atrial pacing within first 20 ms of
      RA activation (10.1 +/- 3.0 cm(2) vs. 3.9+/-1.7 cm(2); p < 0.001). Anatomically,
      the wall of NCAS did not contain myocardial tissue, but was intimately related to
      the paraseptal regions of the atria such that the shortest distances from the
      NCAS to the RA and the left atrium were 1.7 +/- 0.6 mm and 2.3 +/- 0.9 mm (p <
      0.01), respectively. CONCLUSIONS: NCAS-AT has distinct atrial activation patterns
      that can be explained in part by its spatial anatomic relationship with the
      atria.

PMID- 20797496
TI  - Transapical aortic valve implantation in 175 consecutive patients: excellent
      outcome in very high-risk patients.
AB  - OBJECTIVES: The aim of this study was to evaluate the outcome of transapical
      aortic valve implantation in a single center with expanded procedural experience
      and to compare it with predicted risk for conventional aortic valve surgery.
      BACKGROUND: Transapical aortic valve implantation is a new approach for high-risk
      patients with severe aortic stenosis. There are only limited single-center
      experiences with very small numbers of patients. METHODS: Since April 2008,
      transapical aortic valve implantation was performed in 175 consecutive patients.
      The mean patient age was 79.8 +/- 9 years, with a range of 36 to 97 years. The
      mean Society of Thoracic Surgeons score was 23.5 +/- 19.4% (range 2.7% to 89.5%);
      98.3% of patients were in New York Heart Association functional class III or IV.
      Ten patients were in cardiogenic shock. RESULTS: Technical success of the
      procedure was 100%. There was no conversion to conventional surgery.
      Cardiopulmonary bypass was used in 8 patients (6 elective, 2 emergency). The 30
      day mortality was 5.1% for the entire group, 3.6% for all patients without
      cardiogenic shock, and 30% for the patients with cardiogenic shock. Survival at
      1, 6, and 12 months was 94.9%, 85.5%, and 82.6%, respectively. CONCLUSIONS: The
      outcome of transapical aortic valve implantation was very favorable and already
      reproducible during the learning curve. The method has become de facto our
      institutional primary choice for treatment of high-risk patients with severe
      aortic valve stenosis.

PMID- 20797497
TI  - Left ventricular outflow tract ectopy: tiger territory.

PMID- 20797495
TI  - Calcium dynamics and the mechanisms of atrioventricular junctional rhythm.
AB  - OBJECTIVES: The purpose of this study was to test the hypothesis that rhythmic
      spontaneous sarcoplasmic reticulum calcium (Ca) release (the "Ca clock") plays an
      important role in atrioventricular junction (AVJ) automaticity. BACKGROUND: The
      AVJ is a primary backup pacemaker to the sinoatrial node. The mechanisms of
      acceleration of AVJ intrinsic rate during sympathetic stimulation are unclear.
      METHODS: We simultaneously mapped transmembrane potential and intracellular Ca in
      Langendorff-perfused canine AVJ preparations that did not contain sinoatrial node
      (n = 10). RESULTS: Baseline AVJ rate was 37.5 +/- 4.0 beats/min. The wavefront
      from leading pacemaker site propagated first through the slow pathway, then the
      fast pathway and atria. There was no late diastolic Ca elevation (LDCAE) at
      baseline. Isoproterenol up to 3 micromol/l increased heart rate to 100 +/- 6.8
      beats/min, concomitant with the appearance of LDCAE that preceded the phase 0 of
      action potential by 97.3 +/- 35.2 ms and preceded the onset of late diastolic
      depolarization by 23.5 +/- 3.5 ms. Caffeine also produced LDCAE and AVJ
      acceleration. The maximal slope of LDCAE and diastolic depolarization always
      colocalized with the leading pacemaker sites. Ryanodine markedly slowed the rate
      of spontaneous AVJ rhythm. Isoproterenol did not induce LDCAE in the presence of
      ryanodine. The I(f) blocker ZD 7288 did not prevent LDCAE or AVJ acceleration
      induced by isoproterenol (n = 2). CONCLUSIONS: Isoproterenol and caffeine induced
      LDCAE and accelerated intrinsic AVJ rhythm. Consistent colocalization of the
      maximum LDCAE and the leading pacemaker sites indicates that the Ca clock is
      important to the intrinsic AVJ rate acceleration during sympathetic stimulation.

PMID- 20797499
TI  - Ranolazine is effective for acute or chronic ischemic dysfunction with heart
      failure.

PMID- 20797500
TI  - Are Angiotensin-converting enzyme inhibitors and beta-blockers ineffective in
      children with dilated cardiomyopathy and heart failure?

PMID- 20797502
TI  - Coronary stents: current status.
AB  - Coronary artery stents revolutionized the practice of interventional cardiology
      after they were first introduced in the mid-1980s. Since then, there have been
      significant developments in their design, the most notable of which has been the
      introduction of drug-eluting stents. This paper reviews the benefits, risks, and
      current status of Food and Drug Administration-approved drug-eluting stents.

PMID- 20797503
TI  - Coronary stents: looking forward.
AB  - Despite all the benefits of drug-eluting stents (DES), concerns have been raised
      over their long-term safety, with particular reference to stent thrombosis. In an
      effort to address these concerns, newer stents have been developed that include:
      DES with biodegradable polymers, DES that are polymer free, stents with novel
      coatings, and completely biodegradable stents. Many of these stents are currently
      undergoing pre-clinical and clinical trials; however, early results seem
      promising. This paper reviews the current status of this new technology, together
      with other new coronary devices such as bifurcation stents and drug-eluting
      balloons, as efforts continue to design the ideal coronary stent.

PMID- 20797504
TI  - Controversies in dermatology, part III.

PMID- 20797505
TI  - The role of Helicobacter pylori infection in skin diseases: facts and
      controversies.
AB  - Helicobacter pylori is a Gram-negative bacterium that is considered a causative
      agent of peptic ulcer disease, gastric lymphoma, and gastric carcinoma. H pylori
      triggers an intense leucocyte infiltration of the gastric submucosa, an action
      that is mediated by proinflammatory cytokines. Because this pathogenetic
      mechanism is common to many other diseases, H pylori seroprevalence has also been
      investigated in other diseases. H pylori seropositivity is associated with
      various dermatologic disorders. Although the precise role of H pylori is unknown
      in these diseases, the organism can be eradicated, using simple and reliable drug
      regimens. This contribution highlights the dermatologic diseases associated with
      H pylori seropositivity.

PMID- 20797506
TI  - Skin diseases associated with Bartonella infection: facts and controversies.
AB  - The genus Bartonella is composed of a series of species and subspecies. Ten of
      them are responsible for human infections. The best-identified diseases are cat
      scratch disease (B henselae and possibly B clarridgeiae), trench fever (B
      quintana), bacillary angiomatosis (B quintana and B henselae), and the spectrum
      of verruga peruana, Carrion disease, and Oroya fever (B bacilliformis).
      Controversies exist about the implication of a few other microorganisms being
      involved in these diseases. Several other conditions have been associated with
      the presence of Bartonella spp, but these observations await confirmation.

PMID- 20797507
TI  - Skin diseases associated with hepatitis C virus: facts and controversies.
AB  - Hepatitis C virus (HCV) is a common infectious agent and may induce several
      systemic disorders like mixed cryoglobulinemia. In the geographic areas where HCV
      infection is hyperendemic, HCV is the predominant etiologic factor for porphyria
      cutanea tarda and lichen planus. Vasculitides and autoimmune disorders, such as
      sicca syndrome, are probably often related to the virus. Interferon-a2b, which is
      largely used in the treatment of HCV-positive patients, may induce cell-mediated
      autoimmune side effects. Dermatologists may help to identify those patients
      timely.

PMID- 20797508
TI  - Pityriasis rosea and herpesviruses: facts and controversies.
AB  - Pityriasis rosea is an acute exanthem with many clinical and epidemiologic
      features of an infectious disease. To date, human herpesvirus (HHV)-6 and HHV-7
      appear to be the most indicted culprits, and the evidence in favor of this
      hypothesis and the controversial results produced elsewhere are discussed. The
      complex pathophysiology of HHV-6 and HHV-7 infection, their diffusion in the
      population at large, the difficulties of understanding whether the infection is
      still latent or is clinically manifest, and well as whether pityriasis rosea
      depends on a reinfection or on a viral reactivation, all make the issue extremely
      difficult to study and understand.

PMID- 20797509
TI  - Demodex mites: facts and controversies.
AB  - Because Demodex mites are ubiquitous, their potential as human pathogens has
      often been ignored. This contribution focuses on the growing body of evidence
      linking Demodex mites with various skin disorders. Histologically, spongiosis and
      lymphoid inflammation are regularly seen in follicles containing Demodex mites.
      In animals, they are well established as a cause of mange, and a human
      counterpart-demodectic alopecia-appears to exist. There is also a statistical
      association between Demodex mite density and rosacea, facial itching, and chronic
      blepharitis. Papulovesicular rosacealike lesions and spiny blepharitis often
      respond to agents that reduce Demodex numbers. Although these observations are
      not sufficient to fulfill Koch's postulates, Koch's postulates are also not
      fulfilled for the association between brown recluse spiders and dermal necrosis
      or the association between streptococci and guttate psoriasis. The evidence
      linking Demodex mites to human disease has implications regarding treatment.

PMID- 20797510
TI  - Antimicrobials in dermatologic surgery: facts and controversies.
AB  - The two main uses of antimicrobials in dermatologic surgery include prophylaxis
      for bacteremia and prevention of localized surgical skin infection (LSSI).
      Bacteremia can result in hematogenous surgical infections such as infective
      endocarditis and prosthetic joint infection. Comprehensive guidelines from the
      American Heart Society (AHA), American Dental Association (ADA), and the American
      Academy of Orthopedic Surgeons (AAOS) have significantly reduced the number of
      patients in which prophylaxis is indicated for hematogenous surgical infection.
      The use of antimicrobials for localized surgical skin infection in dermatology is
      controversial. Although the overall trend in the literature supports the
      decreased use of antimicrobials in dermatologic surgery as a whole, it is
      important to know which situations still warrant antibiotics. This contribution
      will address the updated guidelines of the AHA, ADA, and AAOS, evidence-based
      techniques to decrease localized surgical skin infections, and situations in
      which antibiotics should be considered during dermatologic surgery.

PMID- 20797511
TI  - Treatment of scabies and pediculosis: facts and controversies.
AB  - Unlike many other skin diseases, success or failure of therapy of ectoparasitic
      infestation depends much more on how to use the topical preparation and whom we
      treat than on which scabicide or pediculicides to use. The diagnosis of scabies
      should no longer rely on the rather uncommon and unpractical sign of finding a
      burrow or the number of parasites per infected patient. Most infested individuals
      have been shown to have several-fold more acari than the oft-quoted average of 12
      adult acari per infected patient that appears in most of our textbooks (stemming
      from Mellanby's work). Contrary to what Mellanby taught us, we know that indirect
      transmission (ie, without personal contact) does occur. As to which agent to use,
      the winner remains undeclared at present. Although indirect contact transmission
      of hair lice has been clarified after thousands of years of infestation, there
      are still numerous questions, uncertainties, disagreements, and controversies on
      the subject; for example, we know that lice survive immersion in water but are
      probably not transmitted in swimming pools. There is no consensus on the best or
      most correct way to diagnose lice, nor is the problem of resistance resolved. We
      do not recommend a "no-nit" policy.

PMID- 20797512
TI  - Chronic wound infection: facts and controversies.
AB  - Chronic wound infections are responsible for considerable morbidity and
      significantly contribute to the escalation in the cost of health care. Wound
      infection may initially be manifest as bacterial colonization, and it is only
      when colonization is combined with other factors, such as decreased vascular
      supply, intrinsic virulence of specific bacteria (eg, Staphylococcus aureus), and
      host immune factors, that true infection occurs. The microbiology of chronic
      wounds is complex, and it is difficult to discern which bacteria are culpable.
      Deep cultures or quantitative biopsies of wound tissue may be necessary. In some
      instances, such as in the presence of certain mycobacteria, isolation of specific
      organisms confirms causation. In many instances, it is appropriate to treat these
      wounds empirically with a combination of topical antiseptics and systemic
      antibiotics, especially in the presence of invasive infections.

PMID- 20797513
TI  - The decubitus ulcer: facts and controversies.
AB  - Defining the decubitus ulcer proves as difficult as agreeing on a name for the
      condition. Causes include pressure over bony prominences, shearing force,
      destruction of skin, and compromised blood flow. Evidence is emerging of the
      importance of ischemia as a primary causative agent, rather than pressure, which
      needs further investigation. Scales, staging, and treatment and prevention
      guidelines should be used with caution due to their arbitrary implementation and
      lack of evidence-based support. Unfortunately, much of the research and expert
      opinion developed by the government and touted as regulation lacks appropriate
      strength-of-evidence. Although decubitus ulcers should be prevented and treated
      to the best of our abilities, recognizing the possibility that the skin, like any
      other organ in the body, may fail is crucial.

PMID- 20797514
TI  - Origins of syphilis and management in the immunocompetent patient: facts and
      controversies.
AB  - Despite the continued efficacy of penicillin since the 1940s, many aspects of the
      natural history, diagnosis, and management of syphilis remain controversial. A
      key factor among the numerous factors explaining the persistence of significant
      areas of controversies is the absence of a gold standard direct method for
      distinguishing between the different stages of syphilis and appraising treatment
      response. This contribution presents an overview of some of the most debated
      aspects of the origins, diagnosis, and management of syphilis in immunocompetent
      patients. The two main current hypotheses on the origins of Treponema pallidum
      are the "Columbian" and the "Pre-Columbian" hypotheses. Strong evidence supports
      that Columbus' crew brought T pallidum to Europe at the time of discovery of the
      New World. Because T pallidum culture and inoculation to animals are not readily
      available methods, the gold standard method for the diagnosis of syphilis is the
      direct identification of T pallidum by dark field microscopy or direct
      fluorescent antibody tests. These methods, however, are inapplicable in many
      patients, and thus the diagnosis of syphilis is usually based on the clinical and
      serologic picture. Serologic tests should only be considered as surrogate markers
      of the disease and do not provide definite distinction between syphilis stages.
      The optimal combination of serologic tests is still undefined. Other areas of
      controversy include the identification of patients who would benefit from a
      lumbar puncture, the diagnostic criteria of neurosyphilis, and the most relevant
      markers of treatment response.

PMID- 20797515
TI  - Management of syphilis in the HIV-infected patient: facts and controversies.
AB  - After reaching an all time low at the turn of the millennium in several
      industrialized countries, the syphilis incidence is rising again, perhaps as a
      consequence of unsafe sexual behavior in response to improved antiretroviral
      therapeutic options for HIV. Since the beginning of the HIV pandemic, numerous
      reports on the various aspects of the interaction between syphilis and HIV have
      been published. Controversies persist on many issues of the management of
      coinfected patients. This contribution presents a critical appraisal of the
      available literature. Few large-scale, properly designed, controlled studies have
      compared syphilis baseline presentation and treatment response according to HIV
      status. Among the weakness are (1) high rates of patients lost to follow-up, (2)
      lack of long-term follow-up, (3) lack of gold standard criteria for treatment
      response, (4) small sample size, and (5) lack of stratification according to
      syphilis stage, ongoing antiretroviral treatment, CD4 cell count and HIV viral
      load. From the available data, and given the ever-possible publication bias, we
      conclude that if HIV has an effect on the course of syphilis, it is small and
      clinically manageable in most cases. The controversial issues discussed should
      furnish the rational for clinical research during the forthcoming decade.

PMID- 20797516
TI  - Treatment of genital warts: facts and controversies.
AB  - There are two opposing approaches in the treatment of genital warts: (1) the
      traditional approach advocates complete elimination of all lesions, and (2) a
      second approach regards condyloma as merely a cosmetic nuisance. After a long
      journey through many arguments and scientific papers, we have concluded that many
      unknowns, uncertainties, and controversies concerning the value of treatment of
      genital warts in terms of clearing and curing the disease (ie, eradicating the
      viruses, preventing cancer, and reducing infectivity). There is no consensus at
      present of whether treatment of men with evidence of genital human papillomavirus
      infection influences the natural history of their female sex partner's cervical
      disease.

PMID- 20797517
TI  - The role of condom use in sexually transmitted disease prevention: facts and
      controversies.
AB  - The role of the condom, as a protective prophylactic device, is one of the most
      important tools, if used appropriately, against the spread of sexually
      transmitted diseases and HIV/AIDS. It should be used by every man, worldwide, who
      is having casual penetrative sex. The word condom is derived from the Latin
      condere. This contribution describes its history from the first descriptions in
      English in the 18th century through rapid improvements in manufacture after the
      commercial cultivation of rubber. The age-old phony arguments against its use by
      men are noted. Recent studies of its acceptability to women are described, as
      well as the introduction of the female condom.

PMID- 20797518
TI  - Evidence-based medicine: facts and controversies.
AB  - Evidence-based medicine is a paradigm shift in the biomedical field toward
      scientific-based clinical practice. It is recognized as the process of acquiring
      and applying into practice the best available research findings in a defined
      filed. Although the roots of evidenced-based medicine date back more than 150
      years, the modern evidenced-based medicine concept has been rapidly and
      constantly developing in the past two decades. Since its introduction, evidenced
      based medicine has simultaneously attracted proponents and critics. This
      contribution provides a critical overview of the major advantages and drawbacks
      of evidenced-based medicine. The discussion and the examples cover the field of
      biomedical research and dermatovenereology in particular.

PMID- 20797519
TI  - Guidelines in dermatology--quo vadis?: Facts and controversies.
AB  - Since their introduction in 1980s, medical guidelines have become a milestone in
      the modern medical practice and science. Being a key feature of modern evidence
      based medicine, guidelines offer the opportunity for unification and
      standardization of diagnostic procedures, their use guarantees the equal access
      of patients to medical service, and they represent a scaffold for inexperienced
      physicians. The implementation of guidelines also can serve as a basis in
      malpractice issues and can contribute to the formation of national and
      international health care policies. In past decades, the process of development,
      update, and practical application of clinical guidelines has been seriously
      improved; however, certain limitations still exist, namely cost-effectiveness
      issues, editorial independence, applicability, accessibility, and external
      validity. This contribution discusses the advantages and the drawbacks in the use
      and the development of medical guidelines, emphasizing future perspectives and
      challenges in the development of clinical guidelines.

PMID- 20797520
TI  - Premalignant nature of oral and vulval lichen planus: facts and controversies.
AB  - Although many classifications include oral lesions of lichen planus in the
      category of a premalignant condition, there is still much discussion about
      whether the mucous membranes lesions should be characterized as an intrinsically
      premalignant condition or merely as a facilitator of the action of a carcinogenic
      factor. The possibility that an epidermoid carcinoma can emerge at the site of
      lichen planus lesions, mainly in mucous membranes, has been shown; however,
      several published cases omit information about other potential risk factors. This
      prevents a complete analysis of the triggering relationship between lichen planus
      and squamous cell carcinoma. This contribution reviews the literature on this
      subject. The question of whether oral or vulval lichen planus, or both, are
      premalignant conditions will only be answered after prospective studies with
      large samples and extensive follow-up are performed, taking into consideration
      the great variety of risk factors involved, together with the establishment of a
      consensus in relation to the points still without agreement.

PMID- 20797521
TI  - Pseudolymphoma and cutaneous lymphoma: facts and controversies.
AB  - Cutaneous pseudolymphoma refers to a heterogenous group of benign reactive T-cell
      or B-cell lymphoproliferative processes of diverse causes that simulate cutaneous
      lymphomas clinically and histologically. Pseudolymphomas may arise in response to
      a wide variety of foreign antigens, but most are idiopathic. Major advances have
      been made in the histologic classification, immunohistochemistry, and molecular
      studies of cutaneous pseudolymphoma. Although this enables a more precise
      differentiation from cutaneous lymphoma, a substantial number of patients still
      present in whom the differential diagnosis is difficult or impossible. Some
      evidence suggests that pseudolymphomas may progress to cutaneous lymphoma due to
      persistent antigenic stimulation. More compelling evidence is needed, especially
      when most cutaneous pseudolymphoma are not associated with known antigens and the
      differentiation from cutaneous lymphoma may be difficult; therefore, a careful
      approach should be used, and the antigenic stimulus should be removed whenever
      possible. A watchful follow-up is warranted in idiopathic cases, and
      consideration should always be given to surgical or medical therapy.

PMID- 20797522
TI  - Periodic scientific publication: reflections on a complex process.

PMID- 20797523
TI  - Nanotechnology and dermatology: part II--risks of nanotechnology.

PMID- 20797524
TI  - Research: a vital mission for ASE.

PMID- 20797527
TI  - Accuracy of right ventricular volumes and function determined by three
      dimensional echocardiography in comparison with magnetic resonance imaging: a
      meta-analysis study.
AB  - BACKGROUND: Determining right ventricular (RV) function is challenging because of
      the complex anatomy of the right ventricle. Three-dimensional echocardiography
      (3DE) has achieved better estimation, but underestimations of volumes and
      ejection fraction (EF) has often been reported, and no previous study has
      synthesized these data. The investigators performed a meta-analysis on the bias
      and examined the related factors. METHODS: Studies comparing RV volumes and/or EF
      between 3DE and magnetic resonance imaging were eligible. A meta-analysis was
      performed to evaluate the systematic bias. The related bias was investigated
      using univariate and multivariate regression analysis. RESULTS: Twenty-three
      studies including 807 subjects revealed underestimation of RV volumes (P <
      .00001) and EF (P = .03). Larger volumes and EF were associated with more
      underestimation. Older patient age was associated with overestimation of volumes
      and underestimation of EF. CONCLUSIONS: This meta-analysis found underestimation
      of RV volumes and EF by 3DE and factors affecting the bias. These data provide a
      more detailed basis for improving the accuracy of 3DE for further clinical
      application.

PMID- 20797528
TI  - Is amyotrophic lateral sclerosis a mitochondrial channelopathy?
AB  - SOD1 is a cause of the fatal, paralytic disorder ALS. Although mechanisms
      underlying mutant SOD1 neurotoxicity remain uncertain, this protein associates
      with mitochondria. In this issue of Neuron, Israelson et al. show that mutant
      SOD1 binds and inhibits the mitochondrial channel VDAC1. This finding sheds light
      onto possible molecular links between mutant SOD1, mitochondrial dysfunction, and
      spinal motor neuron degeneration in inherited ALS.

PMID- 20797529
TI  - Phosphatase activity controls the ups and downs of cerebellar learning.
AB  - Investigations of the cellular substrate for cerebellar learning have focused
      largely on a single form of plasticity, kinase-dependent long-term depression
      (LTD). In this issue of Neuron, Schonewille et al. provide evidence that
      calcineurin, a protein phosphatase required for long-term potentiation (LTP) and
      other cellular processes, may be just as important.

PMID- 20797530
TI  - Petrified or aroused with fear: the central amygdala takes the lead.
AB  - The behavioral expression of fear ranges from active, cognitive responses to
      passive, freezing-like reactions. In this issue of Neuron, Gozzi, Jain, and
      colleagues suggest that neurons in the central amygdala orchestrate output
      signals toward either the brainstem or cholinergic basal forebrain and thereby
      can shift fear reactions from passive to active.

PMID- 20797531
TI  - Neural map formation in the mouse olfactory system.
AB  - Odor signals received by odorant receptors (ORs) in the olfactory epithelium are
      represented as an odor map of activated glomeruli in the olfactory bulb. In the
      mouse olfactory system, it appears that much of axon pathfinding and sorting
      occurs autonomously by olfactory neuron axons. Here, we review the recent
      progress on the study of olfactory map formation in rodents. We will discuss how
      neuronal identity is represented at axon termini and how the OR-instructed axonal
      projection is regulated.

PMID- 20797532
TI  - Neuroeconomic approaches to mental disorders.
AB  - The pervasiveness of decision-making in every area of human endeavor highlights
      the importance of understanding choice mechanisms and their detailed relationship
      to underlying neurobiological function. This review surveys the recent and
      productive application of game-theoretic probes (economic games) to mental
      disorders. Such games typically possess concrete concepts of optimal play, thus
      providing quantitative ways to track when subjects' choices match or deviate from
      optimal. This feature equips economic games with natural classes of control
      signals that should guide learning and choice in the agents that play them. These
      signals and their underlying physical correlates in the brain are now being used
      to generate objective biomarkers that may prove useful for exposing and
      understanding the neurogenetic basis of normal and pathological human cognition.
      Thus, game-theoretic probes represent some of the first steps toward producing
      computationally principled, objective measures of cognitive function and
      dysfunction useful for the diagnosis, treatment, and understanding of mental
      disorders.

PMID- 20797533
TI  - Avoiding DEET through insect gustatory receptors.
AB  - DEET is the most widely used insect repellent worldwide. In Drosophila olfactory
      receptor neurons (ORNs), DEET is detected through a mechanism employing the
      olfactory receptor, OR83b. However, it is controversial as to whether ORNs
      respond directly to DEET or whether DEET blocks the response to attractive odors.
      Here, we showed that DEET suppressed feeding behavior in Drosophila, and this
      effect was mediated by gustatory receptor neurons (GRNs). DEET was potent in
      suppressing feeding as <0.1% DEET elicited aversive behavior. Inhibition of
      feeding required multiple gustatory receptors (GRs) expressed in inhibitory GRNs.
      DEET stimulated action potentials in GRNs that respond to aversive compounds, and
      this response was lost in the Gr32a, Gr33a, and Gr66a mutants. Since 0.02% DEET
      elicited action potentials, we conclude that DEET directly activates of GRNs. We
      suggest that the effectiveness of DEET in pest control owes to its dual action in
      inducing avoidance simultaneously via GRNs and ORNs.

PMID- 20797534
TI  - Targeting single neuronal networks for gene expression and cell labeling in vivo.
AB  - To understand fine-scale structure and function of single mammalian neuronal
      networks, we developed and validated a strategy to genetically target and trace
      monosynaptic inputs to a single neuron in vitro and in vivo. The strategy
      independently targets a neuron and its presynaptic network for specific gene
      expression and fine-scale labeling, using single-cell electroporation of DNA to
      target infection and monosynaptic retrograde spread of a genetically modifiable
      rabies virus. The technique is highly reliable, with transsynaptic labeling
      occurring in every electroporated neuron infected by the virus. Targeting single
      neocortical neuronal networks in vivo, we found clusters of both spiny and aspiny
      neurons surrounding the electroporated neuron in each case, in addition to
      intricately labeled distal cortical and subcortical inputs. This technique,
      broadly applicable for probing and manipulating single neuronal networks with
      single-cell resolution in vivo, may help shed new light on fundamental mechanisms
      underlying circuit development and information processing by neuronal networks
      throughout the brain.

PMID- 20797536
TI  - Rab GTPases-dependent endocytic pathways regulate neuronal migration and
      maturation through N-cadherin trafficking.
AB  - Although membrane trafficking pathways are involved in basic cellular functions,
      the evolutionally expanded number of their related family proteins suggests
      additional roles for membrane trafficking in higher organisms. Here, we show that
      several Rab-dependent trafficking pathways differentially participate in neuronal
      migration, an essential step for the formation of the mammalian-specific six
      layered brain structure. In vivo electroporation-mediated suppression of Rab5 or
      dynamin to block endocytosis caused a severe neuronal migration defect in mouse
      cerebral cortex. Among many downstream endocytic pathways, suppression of Rab11
      dependent recycling pathways exhibited a similar migration disorder, whereas
      inhibition of Rab7-dependent lysosomal degradation pathways affected only the
      final phase of neuronal migration and dendrite morphology. Inhibition of Rab5 or
      Rab11 perturbed the trafficking of N-cadherin, whose suppression also disturbed
      neuronal migration. Taken together, our findings reveal physiological roles of
      endocytic pathways, each of which has specific functions in distinct steps of
      neuronal migration and maturation during mammalian brain formation.

PMID- 20797535
TI  - Misfolded mutant SOD1 directly inhibits VDAC1 conductance in a mouse model of
      inherited ALS.
AB  - Mutations in superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis
      (ALS), a neurodegenerative disease characterized by loss of motor neurons. With
      conformation-specific antibodies, we now demonstrate that misfolded mutant SOD1
      binds directly to the voltage-dependent anion channel (VDAC1), an integral
      membrane protein imbedded in the outer mitochondrial membrane. This interaction
      is found on isolated spinal cord mitochondria and can be reconstituted with
      purified components in vitro. ADP passage through the outer membrane is
      diminished in spinal mitochondria from mutant SOD1-expressing ALS rats. Direct
      binding of mutant SOD1 to VDAC1 inhibits conductance of individual channels when
      reconstituted in a lipid bilayer. Reduction of VDAC1 activity with targeted gene
      disruption is shown to diminish survival by accelerating onset of fatal paralysis
      in mice expressing the ALS-causing mutation SOD1(G37R). Taken together, our
      results establish a direct link between misfolded mutant SOD1 and mitochondrial
      dysfunction in this form of inherited ALS.

PMID- 20797539
TI  - Spatiotemporal response properties of optic-flow processing neurons.
AB  - A central goal in sensory neuroscience is to fully characterize a neuron's input
      output relation. However, strong nonlinearities in the responses of sensory
      neurons have made it difficult to develop models that generalize to arbitrary
      stimuli. Typically, the standard linear-nonlinear models break down when neurons
      exhibit stimulus-dependent modulations of their gain or selectivity. We studied
      these issues in optic-flow processing neurons in the fly. We found that the
      neurons' receptive fields are fully described by a time-varying vector field that
      is space-time separable. Increasing the stimulus strength, however, strongly
      reduces the neurons' gain and selectivity. To capture these changes in response
      behavior, we extended the linear-nonlinear model by a biophysically motivated
      gain and selectivity mechanism. We fit all model parameters directly to the data
      and show that the model now characterizes the neurons' input-output relation well
      over the full range of motion stimuli.

PMID- 20797538
TI  - Purkinje cell-specific knockout of the protein phosphatase PP2B impairs
      potentiation and cerebellar motor learning.
AB  - Cerebellar motor learning is required to obtain procedural skills. Studies have
      provided supportive evidence for a potential role of kinase-mediated long-term
      depression (LTD) at the parallel fiber to Purkinje cell synapse in cerebellar
      learning. Recently, phosphatases have been implicated in the induction of
      potentiation of Purkinje cell activities in vitro, but it remains to be shown
      whether and how phosphatase-mediated potentiation contributes to motor learning.
      Here, we investigated its possible role by creating and testing a Purkinje cell
      specific knockout of calcium/calmodulin-activated protein-phosphatase-2B (L7
      PP2B). The selective deletion of PP2B indeed abolished postsynaptic long-term
      potentiation in Purkinje cells and their ability to increase their excitability,
      whereas LTD was unaffected. The mutants showed impaired "gain-decrease" and "gain
      increase" adaptation of their vestibulo-ocular reflex (VOR) as well as impaired
      acquisition of classical delay conditioning of their eyeblink response. Thus, our
      data indicate that PP2B may indeed mediate potentiation in Purkinje cells and
      contribute prominently to cerebellar motor learning.

PMID- 20797537
TI  - Myosin IIb regulates actin dynamics during synaptic plasticity and memory
      formation.
AB  - Reorganization of the actin cytoskeleton is essential for synaptic plasticity and
      memory formation. Presently, the mechanisms that trigger actin dynamics during
      these brain processes are poorly understood. In this study, we show that myosin
      II motor activity is downstream of LTP induction and is necessary for the
      emergence of specialized actin structures that stabilize an early phase of LTP.
      We also demonstrate that myosin II activity contributes importantly to an actin
      dependent process that underlies memory consolidation. Pharmacological treatments
      that promote actin polymerization reversed the effects of a myosin II inhibitor
      on LTP and memory. We conclude that myosin II motors regulate plasticity by
      imparting mechanical forces onto the spine actin cytoskeleton in response to
      synaptic stimulation. These cytoskeletal forces trigger the emergence of actin
      structures that stabilize synaptic plasticity. Our studies provide a mechanical
      framework for understanding cytoskeletal dynamics associated with synaptic
      plasticity and memory formation.

PMID- 20797540
TI  - Spatial hearing in echoic environments: the role of the envelope in owls.
AB  - In the precedence effect, sounds emanating directly from the source are localized
      preferentially over their reflections. Although most studies have focused on the
      delay between the onset of a sound and its echo, humans still experience the
      precedence effect when this onset delay is removed. We tested in barn owls the
      hypothesis that an ongoing delay, equivalent to the onset delay, is discernible
      from the envelope features of amplitude-modulated stimuli and may be sufficient
      to evoke this effect. With sound pairs having only envelope cues, owls localized
      direct sounds preferentially, and neurons in their auditory space-maps discharged
      more vigorously to them, but only if the sounds were amplitude modulated. Under
      conditions that yielded the precedence effect, acoustical features known to evoke
      neuronal discharges were more abundant in the envelopes of the direct sounds than
      of the echoes, suggesting that specialized neural mechanisms for echo suppression
      were unnecessary.

PMID- 20797541
TI  - A neural switch for active and passive fear.
AB  - The central nucleus of the amygdala (CeA) serves as a major output of this
      structure and plays a critical role in the expression of conditioned fear. By
      combining cell- and tissue-specific pharmacogenetic inhibition with functional
      magnetic resonance imaging (fMRI), we identified circuits downstream of CeA that
      control fear expression in mice. Selective inhibition of a subset of neurons in
      CeA led to decreased conditioned freezing behavior and increased cortical arousal
      as visualized by fMRI. Correlation analysis of fMRI signals identified functional
      connectivity between CeA, cholinergic forebrain nuclei, and activated cortical
      structures, and cortical arousal was blocked by cholinergic antagonists.
      Importantly, inhibition of these neurons switched behavioral responses to the
      fear stimulus from passive to active responses. Our findings identify a neural
      circuit in CeA that biases fear responses toward either passive or active coping
      strategies.

PMID- 20797542
TI  - Moral judgments recruit domain-general valuation mechanisms to integrate
      representations of probability and magnitude.
AB  - Many important moral decisions, particularly at the policy level, require the
      evaluation of choices involving outcomes of variable magnitude and probability.
      Many economic decisions involve the same problem. It is not known whether and to
      what extent these structurally isomorphic decisions rely on common neural
      mechanisms. Subjects undergoing fMRI evaluated the moral acceptability of
      sacrificing a single life to save a larger group of variable size and probability
      of dying without action. Paralleling research on economic decision making, the
      ventromedial prefrontal cortex and ventral striatum were specifically sensitive
      to the "expected moral value" of actions, i.e., the expected number of lives
      lost/saved. Likewise, the right anterior insula was specifically sensitive to
      outcome probability. Other regions tracked outcome certainty and individual
      differences in utilitarian tendency. The present results suggest that complex
      life-and-death moral decisions that affect others depend on neural circuitry
      adapted for more basic, self-interested decision making involving material
      rewards.

PMID- 20797545
TI  - Basic appearance of ultrasound structures and pitfalls.
AB  - The role of ultrasound in musculoskeletal imaging is expanding as technology
      advances and clinicians become better educated about its clinical applications.
      The main use of musculoskeletal ultrasound to physiatrists is to examine the soft
      tissues of the body and to diagnose pathologic changes. Ultrasound can be used to
      assist clinicians in performing interventional procedures. However, to
      successfully integrate this technology into their clinical practices, physicians
      must be familiar with the normal and abnormal appearance of tissues. They also
      must recognize the clinically relevant limitations and pitfalls associated with
      the use of ultrasound.

PMID- 20797546
TI  - Ultrasonography of the shoulder.
AB  - The shoulder is the most common region to be evaluated with musculoskeletal
      ultrasound. The shoulder's complex anatomy enables an exceptional range of
      mobility at the expense of static stability. Consequently, the shoulder is
      susceptible to a multitude of traumatic and atraumatic injuries. This article
      presents an overview of shoulder anatomy, recommends a standardized approach to
      the sonographic shoulder evaluation, and discusses common sonographically
      apparent pathology of the shoulder.

PMID- 20797547
TI  - Ultrasonography of the hand, wrist, and elbow.
AB  - High-frequency diagnostic ultrasonography of the hand, wrist and elbow has
      significant potential to improve the quality of diagnosis and care provided by
      neuromuscular and musculoskeletal specialists. In patients referred for weakness,
      pain and numbness of the hand, wrist or elbow, diagnostic ultrasonography can be
      an adjunct to electrodiagnosis and help in identifying ruptured tendons and
      treating conditions such as carpal tunnel syndrome or trigger finger. Use of a
      small high-frequency (>10-15 MHz) transducer, an instrument with a blunt pointed
      tip to enhance sonopalpation and a model of the hand, wrist and elbow is advised
      to enhance visualization of small anatomical structures and complex bony
      contours. A range of conditions, including tendon and ligament ruptures, trigger
      finger, de Quervain tenosynovitis, intersection syndrome, lateral epicondylitis,
      and osteoarthritis, is described along with detailed ultrasonography-guided
      injection techniques for carpal tunnel syndrome and trigger finger.

PMID- 20797548
TI  - Ultrasonography of the hip and lower extremity.
AB  - Musculoskeletal ultrasonographic evaluation of the proximal lower limb includes
      the evaluation of the soft tissue structures, including tendons, ligaments, or
      muscles, and the bony structures of this region, include the hip, pubic
      symphysis, and sacroiliac joints. The evaluation of the hip or proximal lower
      limb region can be performed in an efficient and systematic manner.
      Ultrasonography of the lateral hip, intra-articular hip, medial thigh, and
      posterior thigh are discussed in the article.

PMID- 20797549
TI  - Musculoskeletal ultrasound of the ankle and foot.
AB  - Despite the tendency for injuries of the foot and ankle to be readily localized
      at physical examination, the examiner is advised to perform an ultrasound
      examination when indicated with a routine and systematic approach. This allows
      for comprehensive evaluation of all the relevant structures and affords the
      necessary experience to recognize abnormal anatomy when it is present.
      Musculoskeletal ultrasound examination strongly complements other diagnostic
      tools used in the diagnosis and treatment of foot and ankle pathology.

PMID- 20797550
TI  - The use of ultrasound in guiding musculoskeletal interventional procedures.
AB  - There has been an increase in the use of ultrasound (US) to help guide
      interventional procedures involving the musculoskeletal system. To perform these
      procedures safely and accurately, two steps must occur. First, the appropriate
      structure must be localized using diagnostic US imaging. Second, a needle must be
      guided under constant visualization toward the targeted tissue. Although US
      imaging can help place the needle and, hence, therapeutic medication more
      accurately, there is still debate about whether or not image-guided procedures
      result in improved outcomes. This article discusses the advantages and
      disadvantages of performing US-guided injections and describes injection
      principles and techniques. Studies examining the efficacy of US-guided procedures
      are reviewed.

PMID- 20797551
TI  - Ultrasonography in regenerative injection (prolotherapy) using dextrose, platelet
      rich plasma, and other injectants.
AB  - Recent advances in ultrasound technology are leading physiatrists to new
      understandings of pain sources, new treatment options, and the ability to guide
      soft tissue interventions. This article examines the role of imaging ultrasound
      in diagnosing soft tissue injury and disease that may respond to regenerative
      medicine techniques (known as prolotherapy) using injectants such as dextrose,
      morrhuate sodium, or platelet-rich plasma. The current state of ultrasound
      evidence for these interventions is reviewed. Case examples assist in
      understanding clinical applications that currently outpace the evidence base.
      Development of quantitative ultrasound measures to objectively evaluate soft
      tissue organization is discussed.

PMID- 20797552
TI  - High-frequency ultrasound guidance for neurotoxin injections.
AB  - In the last decade, advances in ultrasound technology, specifically the
      development of high-frequency linear transducers, have made ultrasound an
      indispensable tool for imaging the musculoskeletal system. Using ultrasound to
      identify target structures for botulinum neurotoxin injection is a natural
      extension of the applications of musculoskeletal ultrasound. The goals of
      incorporating ultrasound with neurotoxin injections are to improve the accuracy
      of needle placement, avoid undesired structures, minimize volume overload during
      injection, and reduce the risk of the procedure. This article provides an update
      on the neurotoxins and their expanded use in clinical practice, and a detailed
      review of the use of ultrasound for the varied indications and applications for
      neurotoxin injection.

PMID- 20797553
TI  - Orthopedic perspectives of musculoskeletal ultrasound.
AB  - Diagnostic ultrasound has been and is becoming an increasingly valuable tool for
      the orthopedic surgeon in the evaluation of the musculoskeletal system.
      Ultrasound has been found to be an extremely important tool in the effective
      evaluation and efficient management of rotator cuff disorders. It helps to
      educate surgeons regarding a patient's shoulder, patients regarding their own
      shoulder, and surgeons regarding the shoulder in general. All of the principles
      acquired through shoulder ultrasound can be applied to the entire musculoskeletal
      system.

PMID- 20797554
TI  - A physiatrist's perspective on musculoskeletal ultrasound.
AB  - Physiatrists are sensitive to the importance of using a diagnostic test as an
      extension of the clinical examination. Training in electrodiagnostic testing
      provides an excellent base to learn about integrating ultrasound into one's
      practice. Given their education in the diagnosis and treatment of
      neuromusculoskeletal disorders and injuries, with an emphasis on quality of life
      and functional gains, ultrasound can help physiatrists design the most
      efficacious and accurate treatment plan. This ultimately provides for adequate
      patient access and improved outcomes.

PMID- 20797556
TI  - Endothelial dysfunction in chronic renal failure.
AB  - Cardiovascular disease is a very early phenomenon in the course of chronic renal
      failure, and increases continuously with decrease of renal function. Endothelial
      dysfunction seems to be a starting point in vascular changes leading to
      atherosclerosis and artery calcification. Endothelium, considered the largest
      organ in the body, has many functions. It senses mechanical and hormonal stimuli
      and in response the endothelial cells secrete a range of compounds which modulate
      vascular tone, coagulation, cell proliferation, and inflammation. The central
      role of endothelium in the development of vascular disease has led to
      identification of new relevant biomarkers and methods to estimate endothelial
      function and injury. Arterial stiffness, which is not an early phenomenon in
      endothelial dysfunction but a common complication of chronic renal failure may be
      evaluated through Pulse Wave Velocity and Augmentation Index obtained by pulse
      wave analysis. Aortic stiffness is an independent predictor of cardiovascular
      morbidity and mortality in patients with hypertension. A new fascinating aspect
      of research in endothelial function is rising through the studies on endothelial
      progenitor cells. These are primitive bone marrow cells that have the ability to
      mature into endothelial cells and have a physiologic role in the repair of
      endothelial lesions.

PMID- 20797557
TI  - Tuberculin skin test, interferon-gamma assay, and T cells subpopulations in
      hemodialysis patients.
AB  - OBJECTIVE: To examine and compare the responses of hemodialysis (HD) patients to
      Mycobacterium tuberculosis antigens by using the tuberculin skin test (TST) and
      an interferon gamma assay (IFN-TB), and to investigate the relationship between T
      cells subpopulations and tests results. Observational, prospective, diagnostic
      study conducted in a HD center in a country with high prevalence of tuberculosis.
      PATIENTS: 195 patients on maintenance HD who consented to participate in this
      study; 187 (6 were excluded for refusing TST and 2 for indeterminate responses to
      IFN-TB) were HIV negative, vaccinated with the Bacille Calmette-Guerin vaccine,
      and without any signs of active tuberculosis, were selected. METHODS: Similar to
      the Mantoux method, 10 IU tuberculin was used for the TST. An IFN-gamma assay
      specific for Mycobacterium tuberculosis antigens and phytohemagglutinin was
      carried out. Flow cytometry analysis of peripheral lymphocytes was also
      performed. RESULTS: TST and IFN-TB results were found to be positive (44% and
      53%, respectively) or negative (32% and 47%, respectively) in similar
      proportions. Results were in agreement in 71% of positive and 58% of negative
      tests. IFN-gamma levels were found to be higher in patients with a positive TST.
      All cell counts and CD4/CD8 were found to be higher in TST-positive patients,
      whereas only total lymphocytes count and CD4/CD8 were reported to be high in IFN
      TB-positive patients. A model of multivariable linear regression including cell
      counts explained 16% of the mitogen-induced IFN-gamma production (F = 5,11; P =
      .0003). The majority of subjects with positive tests were younger, in most cases
      male, belonged to the Roma ethnic group, had a shorter HD vintage, and a better
      nutritional status. CONCLUSIONS: TST and IFN-gamma production stimulated by
      Mycobacterium tuberculosis antigens rely on patient's immune status, which could
      be influenced by either individual (age, gender), dialysis-related (HD vintage),
      or nutritional factors. In addition, the diagnostic utility for tuberculosis is
      similar and moderate in HD patients.

PMID- 20797558
TI  - Hydrogen sulfide, the third gaseous signaling molecule with cardiovascular
      properties, is decreased in hemodialysis patients.
AB  - Hydrogen sulfide, H(2)S, is the third endogenous gas with cardiovascular
      properties, after nitric oxide and carbon monoxide. H(2)S is a potent
      vasorelaxant, and its deficiency is implicated in the pathogenesis of
      hypertension and atherosclerosis. Cystathionine beta-synthase, cystathionine
      gamma-lyase, and 3-mercaptopyruvate sulfurtransferase catalyze H(2)S formation.
      Chronic kidney disease is characterized by high prevalence of
      hyperhomocysteinemia, hypertension, and high cardiovascular mortality, especially
      in hemodialysis patients. H(2)S levels are decreased in hemodialysis patients
      through transcriptional deregulation of genes encoding for the H(2)S-producing
      enzymes. Potential implications relate to the pathogenesis of the manifestations
      of the uremic syndrome, such as hypertension and atherosclerosis.

PMID- 20797559
TI  - The effect of type and vascular access quality on the outcome of chronic
      hemodialysis treatment.
AB  - The function of vascular access has a key significance in hemodialysis treatment
      results. An overview of factors contributing to successful arteriovenous fistula
      (AVF) constructions and the effect of vascular access quality on the outcome of
      renal replacement therapy were analyzed, including our study observations. On the
      basis of the data obtained in the study, the creation of autogenous AVF was
      reported to be possible in 92.9% of the 213 investigated patients. In 81.2% of
      the patients, vascular access was found to be located on the forearm.
      Comorbidities, especially congestive heart failure and peripheral vascular
      disease, were the main factors that had a negative effect on AVF construction and
      quality. AVF abnormalities were detected on physical examination in 37% of the
      patients. Results from the physical examination were found to be consistent with
      those obtained from Doppler ultrasound, thermodilution, and intra-access pressure
      measurement. AVF stenosis significantly increased the risk for access thrombosis,
      catheter insertion, and vascular access-related hospitalization.

PMID- 20797560
TI  - Progress toward novel treatments for chronic kidney disease.
AB  - Chronic kidney failure remains a major health problem worldwide. Although current
      treatment is focused on the renin-angiotensin system, it is essential that new
      treatments targeted toward novel pathophysiological mechanisms are developed if
      we are to make significant progress in this area. In this review, we have
      outlined several promising new areas while emphasizing that large, randomized,
      well-controlled clinical trials are essential to reach a meaningful conclusion
      about the efficacy and safety of novel treatment.

PMID- 20797561
TI  - Why we need clinical practice guidelines in chronic kidney disease.
AB  - Clinical practice guidelines (CPGs) have become an essential, useful, and
      integral part of the practice of medicine in general and for the care of patients
      with chronic kidney disease (CKD) in particular. The reasons why CPGs have proven
      useful are related to the need of physicians, patients, and providers. Physician
      needs stem from the overwhelming amount of new information generated that
      requires systematic analysis, synthesis, and translation into specific clinically
      applicable recommendations. Patient needs arise from the desire of an
      increasingly well-informed public seeking evidence-based information in making
      joint decisions with their physicians. Provider needs derive from the necessity
      of appropriate criteria in assessing improved outcomes and in closing existing
      quality chasms in health care delivery. It is in the one patient one physician
      clinical encounter setting that guidelines are likely at their best in helping
      make appropriate decisions in each specific situation. All other uses of CPGs, no
      matter how meritorious, are secondary derivatives.

PMID- 20797562
TI  - Uremia (end-stage renal disease): how cost-effective are preventive strategies?
AB  - Many strategies have been shown to be cost-effective for prevention of end-stage
      renal disease (ESRD), most often by Markov modeling using assumptions based on
      randomized clinical trails and observational studies. Targeted screening for
      proteinuria in diabetics and in hypertensive patients is cost-effective for
      prevention of ESRD, but such screening is not cost-effective when applied to the
      general population. Screening for chronic kidney disease based on estimated
      glomerular filtration rate alone is not recommended. Perhaps, treatment of all
      newly diagnosed type 2 diabetics with an inhibitor of angiotensin-II without
      screening for proteinuria will also prevent or delay ESRD in a cost-effective
      manner. Intensive interventions and the use of angiotensin-II inhibition in
      incipient and overt nephropathy in type 1 and type 2 diabetes is also cost
      effective in preventing ESRD. Rigorous control of blood pressure to desired
      targets also lowers the risks of ESRD in both diabetic and nondiabetic
      nephropathies, most likely in a cost-effective manner. Newer strategies involving
      statins and new combinations of agents are emerging but have not yet been tested
      for their cost-effectiveness in preventing ESRD cost-effectiveness.

PMID- 20797563
TI  - Novel kidney injury biomarkers.
AB  - New biomarkers are currently under development for acute kidney injury and
      chronic kidney disease. Panels of validated biomarkers are most likely to be
      required to obtain information that will help in delineating acute versus chronic
      disease, the pathogenetic nature of the process, the severity, and the capacity
      for reversibility. Glycoprotein non-metastatic melanoma protein-b, a protein
      associated with regulation of inflammation and autophagy, is in an intermediate
      stage of development as a kidney injury biomarker.

PMID- 20797564
TI  - Metabolic syndrome and chronic kidney disease.
AB  - Obesity is a global health threat because of its associated metabolic and
      cardiovascular complications. Metabolic and hemodynamic complications of obesity
      (insulin resistance and hyperglycemia, hypertension, atherogenic dyslipidemia)
      are often clustered in the metabolic syndrome, leading to high cardiovascular
      morbidity and mortality. In recent years, epidemiological studies have clearly
      indicated that both obesity and the metabolic syndrome are independent risk
      factors for chronic kidney disease and these associations are at least in part
      independent of diabetes and hypertension per se. Additional mechanisms associated
      with obesity and metabolic syndrome leading to reduced renal function may include
      altered levels of adipose tissue hormones, inflammation, and oxidative stress.
      The ongoing worldwide obesity epidemic is therefore likely to increase the number
      of patients with chronic uremia and features of the metabolic syndrome in the
      next few years. Moreover, the onset and maintenance of renal damage may worsen
      metabolic syndrome features including insulin resistance and hypertension,
      leading to potential vicious cycles with negative clinical effect. Further
      understanding of the interactions between obesity, metabolic syndrome, and
      chronic kidney disease represents a potential strategy to design more effective
      treatments aimed at reducing morbidity and mortality in uremic patients.

PMID- 20797565
TI  - Indoxyl sulfate is a nephro-vascular toxin.
AB  - Indoxyl sulfate is markedly accumulated in the serum of patients with chronic
      kidney disease (CKD). The oral sorbent AST-120 reduces the serum levels of
      indoxyl sulfate in CKD patients by adsorbing indole, a precursor of indoxyl
      sulfate, in the intestine, and thereby stimulating its excretion in feces. AST
      120 is used for the treatment of patients with CKD to slow down the progression
      of CKD. Indoxyl sulfate is taken up by the cells through organic anion
      transporters (OAT1 and/or OAT3), and induces cellular production of free radicals
      such as superoxide by activating nicotinamide adenine dinucleotide phosphate
      oxidase, especially Nox4, thereby impairing the cellular antioxidative system.
      Indoxyl sulfate induces free radicals in renal tubular cells and glomerular
      mesangial cells, and stimulates the progression of CKD. I proposed the protein
      metabolite theory, which states that endogenous protein metabolites such as
      indoxyl sulfate play a significant role in the progression of CKD by increasing
      expressions of transforming growth factor-beta1, tissue inhibitor of
      metalloproteinase-1, and proalpha1(I)collagen. Indoxyl sulfate also induces free
      radicals in vascular smooth muscle cells and vascular endothelial cells. Indoxyl
      sulfate stimulates proliferation and osteoblastic transdifferentiation of
      vascular smooth muscle cells, and inhibits viability and nitric oxide production
      of vascular endothelial cells. Indoxyl sulfate promotes aortic calcification and
      aortic wall thickening in hypertensive rats with expression of osteoblast
      specific proteins. In conclusion, indoxyl sulfate is a nephro-vascular toxin that
      is involved in the progression of not only CKD, but also of cardiovascular
      disease in CKD patients. Therefore, AST-120 may ameliorate the progression of
      cardiovascular disease as well as of CKD by removing indoxyl sulfate.

PMID- 20797566
TI  - Muscle atrophy in chronic kidney disease results from abnormalities in insulin
      signaling.
AB  - Muscle atrophy is a significant consequence of chronic kidney disease that
      increases a patient's risk of mortality and decreases their quality of life. The
      loss of lean body mass results, in part, from an increase in the rate of muscle
      protein degradation. In this review, the proteolytic systems that are activated
      during chronic kidney disease and the key insulin signaling pathways that
      regulate the protein degradative processes are described.

PMID- 20797567
TI  - Obesity and chronic kidney disease.
AB  - Obesity is a common contributing factor to the development of chronic kidney
      disease (CKD). Obesity participates in the genesis of CKD by predisposing to
      diabetic nephropathy, hypertensive nephrosclerosis, and focal and segmental
      glomerular sclerosis. It also predisposes to calcium oxalate and urate stones.
      Additionally, obesity is associated with an increased prevalence and magnitude of
      proteinuria and a more rapid progression to CKD. There are many mechanisms by
      which obesity alters renal physiology and metabolism. More effective methods for
      treating obesity and preventing the development and progression of obesity
      associated CKD are clearly needed. Therefore, there is a greater need for a
      better understanding of the causes of the excessive energy intake that leads to
      obesity and the mechanisms responsible for the refractoriness of obese
      individuals to treatment.

PMID- 20797568
TI  - Nutritional intervention in uremia--myth or reality?
AB  - Nutritional intervention in uremia, specifically the restricted protein diet, has
      been under debate for decades. The results of various clinical trials have not
      been concordant, as some studies have reported positive effects of the low
      protein diets, whereas others have shown no benefit. Recently published data show
      that the restricted protein diets seem to be effective and safe in ameliorating
      nitrogen waste products retention and the disturbances in acid-base and calcium
      phosphorus metabolism, and in delaying the initiation of renal replacement
      therapy (RRT), without any deleterious effect on the nutritional status of
      patients with chronic kidney disease. The nutritional support and particularly
      the supplemented very low protein diet could be a new link to the RRT-integrated
      care model. A possible delay in RRT initiation through nutrition could have a
      major economic effect, particularly in developing countries, where the dialysis
      facilities still do not meet the requirements. However, a careful selection of
      motivated patients who could benefit from such a diet, closer nutritional
      monitoring, and dietary counseling are required.

PMID- 20797569
TI  - Lipotoxicity and impaired high density lipoprotein-mediated reverse cholesterol
      transport in chronic kidney disease.
AB  - Chronic kidney disease (CKD) is associated with a high risk of death from
      cardiovascular disease. Inflammation, oxidative stress, and dyslipidemia, which
      are common consequences of CKD, contribute to the pathogenesis of atherosclerosis
      and cardiovascular disease in this population. Dyslipidemia of CKD is
      characterized by diminished plasma high density lipoprotein (HDL) concentration,
      impaired HDL anti-oxidant and anti-inflammatory activities, and elevated plasma
      triglyceride, very low density lipoprotein (VLDL), intermediate density
      lipoprotein, chylomicron remnants, and oxidized lipids and lipoproteins. The
      constellation of inflammation, HDL deficiency, and oxidative modification of
      lipoproteins can cause atherosclerosis and progression of renal disease. We have
      recently found lipid accumulation in the remnant kidney and the wall of aorta in
      rats with CKD induced by 5/6 nephrectomy. This was mediated by up-regulation of
      scavenger receptors involved in the influx of oxidized lipids or lipoproteins,
      tubular reabsorption of lipid binding proteins through megalin-cubilin complexes,
      upregulation of fatty acid synthesis, and downregulation of fatty acid oxidation
      pathways. The combination of increased lipid influx, elevated production and
      reduced catabolism of lipids, and impaired HDL-mediated reverse cholesterol
      transport can promote atherosclerosis, glomerulosclerosis, and tubulointerstitial
      damage. Although statins can be effective in slowing CKD progression in patients
      with mild-to-moderate CKD, they have consistently failed to mitigate oxidative
      stress, inflammation, HDL deficiency, or cardiovascular mortality in the end
      stage renal disease populations. Similarly, high doses of antioxidant vitamins
      have failed to either ameliorate oxidative stress, inflammation, or improve
      overall mortality in end-stage renal disease. This article is intended to provide
      a brief review of the effects of CKD on HDL structure and function and pathways
      of lipid influx, efflux, synthesis, and catabolism in the artery wall and the
      diseased kidney.

PMID- 20797570
TI  - Mechanisms of acute uremic encephalopathy: early activation of Fos and Fra-2 gene
      products in different nuclei/areas of the rat brain.
AB  - High levels of various uremic toxins such as guanidino compounds and advanced
      glycation endproducts, as well as an excess of parathyroid hormones, are involved
      in the pathogenesis of acute uremic encephalopathy. Moreover, distant effects of
      the damaged kidney with enhanced production of inflammatory mediators are
      implicated. Data on the pump activity of an abnormal Na-K-ATPase and inhibition
      of the organic anion transporter system in the brain have been published
      previously. Recently, the effect of an experimentally induced acute renal failure
      (ARF) on the neuronal cell activation of Fos and Fra-2 in the rat brain was
      investigated by immunohistochemistry. ARF was induced by using the following 3
      rat models: bilateral nephrectomy, bilateral ureter ligation, and uranyl acetate
      injection with corresponding controls. The Fos and the Fra-2 immunoreactive
      neurons of the brain were determined in a total of 120 brain areas over a period
      of 3 days post bilateral nephrectomy and bilateral ureter ligation and 12 days
      after uranyl acetate. An activation response was observed in 73 of 120 areas of
      the brain. The responses were classified into 4 groups: (1) biogenic amines
      (noradrenaline, adrenaline, histamine, and 5-hydroxytryptamine), (2) stress
      sensitive forebrain areas, (3) neuronal cell groups involved in the regulation of
      water and electrolyte homeostasis, and (4) central autonomic cell groups. In the
      uranyl acetate-induced ARF, activation of Fos and Fra-2 immunoreactivity took
      place at the earliest time-point (3 hours) which persisted even after improvement
      of ARF. This suggests the involvement of the toxic effects of uranium as a result
      of its accumulation in the brain.

PMID- 20797571
TI  - A controlled study of psychiatric manifestations and electroencephalography
      findings in chronic kidney disease patients with Sagliker syndrome.
AB  - Sagliker syndrome (SS) is a novel syndrome that was described in 2004 in patients
      with chronic kidney disease (CKD). The aim of this study was to assess
      psychiatric evaluations and electroencephalography (EEG) findings of patients
      with CKD and SS to compare them with patients with CKD having characteristics
      similar to that of the study group, in terms of age and gender. The study group
      comprised 13 patients with CKD and SS. The control group included 13 patients
      with CKD. Psychiatric diseases were diagnosed using the Structure Clinical
      Interview. Beck Depression Inventory, Beck Anxiety Inventory, Social Comparison
      Scale, Hopelessness Scale, and Mini Mental State Examination (MMSE) were
      administered to the groups. Moreover, EEG recording for all the patients was
      performed. According to the results obtained from the Structure Clinical
      Interview, 69.2% of patients with CKD and SS were diagnosed with a mental
      disease, as compared with only 3 (23.1%) patients with CKD. There was a
      significant difference between the study and the control group (P < .001). As
      compared with the control group, patients with CKD and SS had significantly
      higher scores on the Beck Depression Inventory, the Beck Anxiety Inventory, and
      the Hopelessness Scale. However, patients with CKD and SS had significantly lower
      scores on the Social Comparison Scale. The MMSE scores were not significantly
      different between the 2 groups. When the 2 groups were evaluated separately, no
      significant differences were found between the EEG abnormalities and psychiatric
      diagnosis of both the groups. However, an evaluation of EEG abnormalities in all
      cases with CKD suggested a statistically significant difference between them. In
      the EEG recordings, electrical seizures activity was not enrolled in any of the
      cases. In the present study, psychiatric morbidity for patients with CKD and SS
      was worse than for patients with only CKD. These results indicate a need to
      develop an effective psychologic strategy for dealing with psychiatric disorders
      among patients with CKD and SS.

PMID- 20797572
TI  - Audiological findings in chronic kidney disease patients with Sagliker syndrome.
AB  - Potential hearing loss was found to be high in a 10 patients with chronic kidney
      disease and Sagliker syndrome. The cause of hearing loss in these subjects
      remains unknown. We do not know whether those are the results of preexisting
      renal disease, hemodialysis, or other factors. Thus, future studies will include
      more subjects with Sagliker syndrome to determine the frequency of hearing loss
      and to investigate the etiologic factors that cause loss of hearing.

PMID- 20797573
TI  - A longitudinal study of sleep disorders in early-stage chronic kidney disease.
AB  - Few studies have addressed the problem of sleep disturbances in patients with
      early-stage chronic kidney disease (CKD). A total of 220 patients newly diagnosed
      with CKD and 220 patients newly diagnosed with chronic hepatitis C were studied
      within 1 month from the diagnosis. They were evaluated by using the Charlson
      Comorbidity Index, the Pittsburgh Sleep Quality Index, and the Beck Depression
      Inventory. Patients with CKD were followed up for 4 years. Sleep disturbances
      affected 59.5% of patients with chronic hepatitis C and 84.6% of patients with
      CKD. Sleeping disorders that were severe and peculiar in early CKD improved
      significantly over time. Beck Depression Inventory disclosed significant
      depression, which was ameliorated over time. Charlson Comorbidity Index was
      constant over time. Logistic regression analysis failed to detect significant
      correlations for putative factors emerging from studies in hemodialyzed patients,
      with the exception of depression.

PMID- 20797574
TI  - The high prevalence of alexithymia in hemodialyzed patients with secondary
      hyperparathyroidism unsuppressed by medical therapy is cured by
      parathyroidectomy.
AB  - There are scanty data available on alexithymia in patients with end-stage renal
      disease, which point to an independent association with depression and social
      support. This study was devised to investigate the prevalence of alexithymia and
      sleep disorders in patients maintenance hemodialysis with insuppressible
      secondary hyperparathyroidism, who need parathyroidectomy (PTX), because previous
      data from our laboratories as well as those of others showed that this patient
      group are the worst sleepers among hemodialysis patients with end-stage renal
      disease. A total of 40 patients needing PTX were enrolled and studied before the
      surgery. As for the control group, 80 patients on maintenance hemodialysis not
      needing PTX were enrolled. We measured alexithymia with the Toronto Alexithymia
      Score (TAS-20), sleep disorders with the Pittsburgh Sleep Quality Index (PSQI),
      and depression with Beck Depression Inventory (BDI), intact parathyroid hormone
      (iPTH), calcium, phosphate, use of antihypertensives, systolic and diastolic
      blood pressure, hemoglobin concentration, and albumin concentration. Patients
      needing PTX in comparison with those not needing PTX had significantly higher
      iPTH, calcium, and phosphate; they also had significantly higher systolic and
      diastolic blood pressure. They were more significantly alexithymic (P < .001),
      had more severe sleep disorders (P < .001), and were more depressed (P < .043).
      In multivariate analysis, BDI correlated significantly with iPTH concentration (r
      = 0.505, P < .001). A reduction of TAS-20 occurred after PTX which correlated
      with the number of patients on antihypertensive drugs, PSQI, BDI, hemoglobin
      concentration in the univariate and multivariate analysis. When TAS-20 and PSQI
      were adjusted for BDI (using analysis of variance) there was still a significant
      difference of TAS-20 and PSQI between patients needing PTX and not needing PTX (P
      < .001). This study confirms the high prevalence of sleep disorders in patients
      with unsuppressed secondary hyperparathyroidism and discloses a high prevalence
      of Alexithymia which is ameliorated by PTX. However, the correlation of
      Alexithymia with sleep disorders does not depend on depression.

PMID- 20797575
TI  - Distribution of purine nucleotides in uremic fluids and tissues.
AB  - There are almost 100 different substances called uremic toxins. In this study, we
      analyze all findings concerning the new family of uremic compounds--nicotinamide
      end products: N-methyl-2-pyridone-5-carboxamide (Met2PY), N-methyl-4-pyridone-5
      carboxamide, newly described 4-pyridone-3-carboxamide-1-beta-D-ribonucleoside
      (4PYR) and 4-pyridone-3-carboxamide-1-beta-D-ribonucleoside triphosphate (4PYTP).
      After few years of studies, we have found that these substances have higher
      plasma concentration in patients with chronic renal failure (CRF) in comparison
      with the healthy population. We noted a 40-fold increase in plasma 4PYR
      concentration in patients with CRF. This increment correlates significantly with
      the decline of kidney function measured as an increase of serum creatinine
      concentration and decrease of estimated glomerular filtration rate. Tested
      compounds are present and measurable in physiological fluids and tissues. We
      found higher saliva Met2PY concentration in patients with CRF in comparison with
      controls. Saliva Met2PY correlated negatively with estimated glomerular
      filtration rate and positively with serum creatinine concentration. One-third of
      studied group had higher concentration of Met2PY in the saliva than in plasma,
      and this segment of patients may be called as "good excretors." In rats with
      experimental CRF, we found that both Met2PY and N-methyl-4-pyridone-5-carboxamide
      accumulated in selected tissues. We also demonstrated formation of 4PYTP in
      intact human erythrocytes during incubation with the precursor 4PYR. Incubation
      with 4PYR leads to lowering concentration of adenosine-5'-triphosphate. 4PYTP
      formation may be a way to remove 4PYR from the circulation and save adenosine-5'
      triphosphate depletion. Summarizing, end products of the nicotinamide family are
      members of uremic toxins; however, exact pathophysiological role of these
      compounds in the development of uremic syndrome needs further studies.

PMID- 20797576
TI  - Oxidative stress, renal anemia, and its therapies: is there a link?
AB  - In chronic kidney disease, anemia and oxidative stress are common features and
      both are involved in increasing morbidity and mortality. However, their
      relationship is still a matter of debate. This article is a review of published
      data and our experience and is intended to debate the pro and contra arguments
      concerning renal anemia and its 2 main therapeutic approaches, that are,
      erythropoietin and intravenous iron supplementation, as additional causes of
      oxidative stress in end-stage renal disease patients. To date, it seems more
      likely that renal anemia itself is the main contributor, and intravenous iron
      further enhances oxidative stress associated with chronic kidney disease. Future
      randomized prospective trials, with "hard" clinical end-points, are needed to
      establish the real effect of biochemical pro-oxidative changes on patient's
      outcome.

PMID- 20797577
TI  - Is hepcidin-25 a clinically relevant parameter for the iron status in
      hemodialysis patients?
AB  - BACKGROUND: Accumulating data suggest potential clinical relevant relationships
      between hepcidin-25 levels, iron stores, erythropoiesis effectiveness, and
      epoetin dose. The immunometric methods and mass spectroscopy are currently used
      to measure hepcidin-25, but no standard exists, and values, although similar in
      trends, differ in absolute value. OBJECTIVE: To investigate hepcidin levels and
      their relationship with peripheral iron indices, inflammation, and anemia therapy
      in patients on hemodialysis (HD). METHODS: A cross-sectional study in 78 patients
      from a single HD center. Hepcidin-25 was measured with enzyme-linked
      immunosorbent assay (ELISA), using a commercial kit (Bachem, UK). RESULTS:
      Hepcidin-25 levels were similar to those previously reported in studies using the
      same antibody (median 113 [95% CI; 107-122 ng/mL]) and significant but weak
      correlations of hepcidin with transferrin (R2=0.06; p<0.04) and ferritin
      (R2=0.09; p<0.01) were found. A model of multiple regression analysis explained
      57% of variation along hepcidin quartiles. Lower hepcidin levels were associated
      with higher transferrin levels (odds ratio 1.05 [1.01-1.09]), bigger iron doses
      (odds ratio 1.09 [1.02-1.15]), and an increased darbepoetin resistance index
      (odds ratio 4.3E+15 [11.15-1.6E+30]). An elevated serum C reactive protein was
      associated with increased hepcidin levels (odds ratio 0.70 [0.49-0.99]), while a
      higher ultrafiltration volume (odds ratio 4.30 [1.28-14.51]) and the male sex
      (odds ratio 0.04 [0.00-0.80]) were related to lower hepcidin levels. LIMITS:
      Cohort number and composition. Hepcidin-25 ELISA assay. CONCLUSION: A low
      hepcidin level in hemodialysis patients with high epoetin resistance index could
      be a useful marker of iron-restricted erythropoiesis, but confirmation by a
      therapeutical trial is necessary.

PMID- 20797578
TI  - Red cell survival: relevance and mechanism involved.
AB  - Red blood cells (RBCs) often have a short circulating half-life in hemodialysis
      patients, which increases the difficulty of achieving a stable hemoglobin level.
      Fluctuations in erythropoietin (EPO) levels contribute to this increased RBC
      turnover because a decline in the level of EPO triggers the preferential
      destruction of newly-formed RBC, a process termed neocytolysis. The RBCs that are
      released during the treatment of renal anemia are often hypochromic, with a low
      content of iron; these RBCs are vulnerable to rapid turnover because iron
      deficiency affects RBCs in several ways, such as, increased exposure of the
      phagocytic signaling molecule phosphatidylserine, loss of deformability, and
      increased oxidative stress. Both EPO fluctuation and the release of iron
      deficient RBCs are characteristic events occurring during the management of renal
      anemia, and the shorter RBC lifetime is a component of the large fluctuations in
      hemoglobin level seen in patients on hemodialysis.

PMID- 20797579
TI  - Skin blood flow in patients with stage 5 chronic kidney disease on hemodialysis.
AB  - We have shown previously that skin perfusion is reduced in patients with diabetes
      mellitus (DM). Patients with diabetes and with chronic kidney disease (CKD) stage
      5 were having advanced microangiopathy. In this cross-sectional study, we
      measured skin blood flow in DM and non-DM patients on dialysis to assess whether
      any differences exist in skin perfusion in those 2 groups of patients. A total of
      25 patients with DM (aged 59.9 +/- 2.2 years) and 24 patients with non-DM CKD
      stage 5 (44.6 +/- 2.9 years) on hemodialysis (HD) were studied. Ten healthy
      subjects (37 +/- 4.3 years) were used as a control group. Skin blood flow (SBF)
      was measured using Vasamedic Model 403B laser Doppler device (Vasamedics Inc.,
      St. Paul, MN) in a standardized way at the plantar and dorsal surface of the
      finger and toe and at the pretibial surface of the leg at 2 different local skin
      temperatures of 35 degrees C and 44 degrees C. Laboratory biochemical data were
      collected at the time of SBF study. The SBF measured at 35 degrees C was lower in
      the patients with DM on dialysis as compared with healthy subjects and non-DM
      dialysis patients. The SBF response to the increase in temperature of the probe
      to 44 degrees C was 70% to 80% lower in DM patients as compared with healthy
      subjects and non-DM patients. However, non-DM subjects who displayed SBF similar
      to control subjects at 35 degrees C, had impaired response in SBF at 44 degrees C
      as well. Patients with lower serum albumin exhibited lower SBF even after
      adjustment for age. SBF is impaired in patients with stage 5 CKD on HD,
      particularly in those with DM as a cause of CKD. SBF negatively correlated with
      age and albumin (nutritional status) in DM and non-DM patients with stage 5 CKD
      on HD. Measurement of SBF can be useful in the evaluation of vasculopathy in CKD
      population and can potentially be used for assessment of vascular response during
      specific clinical intervention.

PMID- 20797580
TI  - Vitamin B6 and oxalic acid in clinical nephrology.
AB  - OBJECTIVE: Vitamin B(6) (VB(6)) is a water-soluble vitamin, which is important
      for the normal functioning of multiple organ systems. It is metabolized to the
      active molecule pyridoxal-5-phosphate (PLP). Oxalic acid (OA) is thought to be a
      uremic toxin that participates in the pathogenesis of the uremic syndrome. The
      objectives of this study were as follows: (1) to evaluate the plasma and
      erythrocyte VB(6) (effect of PLP; effect of PLP was in indirect relationship with
      the concentration of erythrocyte VB(6)), and plasma and urinary OA in marathon
      runners, in patients with acute intermittent porphyria (AIP) and variegate
      porphyria, and in patients with stage 1 chronic kidney disease (CKD), chronic
      glomerulonephritis and nephrotic syndrome (CGNS); (2) to examine the influence of
      water diuresis in healthy subjects, and the influence of sodium diuresis (high
      sodium intake) and an intravenous administration of furosemide on the urinary
      excretion of VB(6) and OA in CKD stage 3-4 patients; and (3) to evaluate the
      influence of erythropoietin treatment on erythrocyte VB(6) (effect of PLP) in
      hemodialysis (HD) patients, and the influence of continuous ambulatory peritoneal
      dialysis (CAPD) therapy on plasma VB(6) and OA and their peritoneal clearance and
      transfer. DESIGN AND SETTING: This study was conducted at the Nephrological
      Clinic of L. Pasteur Faculty Hospital and of Medical School of P. J. Safarik
      University. A combination of 29 marathon runners, 15 patients with CG and NS, 11
      patients with AIP, 1 patient with variegate porphyria, 15 healthy subjects, 27
      CKD stage 3-4 patients, 30 HD, and 27 CAPD patients were used in the study.
      RESULTS: After a marathon run, plasma and erythrocyte VB(6) significantly
      decreased and plasma OA increased. Plasma (15.5 +/- 3.8 nmol/L) and erythrocyte
      VB(6) (effect of PLP: 42.1% +/- 7.5%) were decreased and plasma OA (9.8 +/- 2.3
      micromol/L) was significantly elevated in patients with CGNS and stage 1 CKD. In
      patients with AIP, deficiency of plasma (24.3 +/- 5.2 nmol/L) and erythrocyte
      VB(6) (effect of PLP: 46.2% +/- 7.0%) and hyperoxalemia (9.39 +/- 2.5 micromol/L)
      were present. The urinary excretion of VB(6) and of OA during maximal water
      diuresis and after intravenous administration of furosemide increased
      significantly (P < .01), but was not affected by the high intake of NaCl (P >
      .05). Erythropoietin treatment in HD patients led to the erythrocyte VB(6)
      deficiency. This finding is an indirect evidence that erythrocyte VB(6) is
      consumed by the hemoglobin synthesis much more during EPO treatment. In CAPD
      patients, plasma value of VB(6) (127.3 +/- 66.9 micromol/L) was in the normal
      range and plasma OA (23.6 +/- 7.4 micromol/L) was significantly elevated. Mean
      value of peritoneal clearance of VB(6) was 8.8% and of OA was 76.9% of urea
      clearance. CONCLUSION: Our study indicates that deficiency of VB(6) led to
      hyperoxalemia and hyperoxaluria in patients with CKD. Deficiency of VB(6) in CKD
      stage 4-5 patients potentiates the uremic hyperoxalemia and hyperoxaluria.

PMID- 20797582
TI  - "Take your government hands off my Medicare".

PMID- 20797583
TI  - The modified Kidner-Cobb procedure for symptomatic flexible pes planovalgus and
      posterior tibial tendon dysfunction stage II: review of 50 feet in 39 patients.
AB  - Symptomatic flatfoot is a prevalent disorder. We undertook a review of 50 feet in
      39 patients with flexible flatfoot treated between August 2000 and January 2008
      in order to evaluate the modified Kidner-Cobb procedure. Overall clinical results
      were rated as good in 48 (96%) feet and fair in 2 (4%) feet, and there were no
      poor results. Average follow-up was 4.6 years, and total recovery time was 5.7
      months in older patients and 3.7 months in children. Manual muscle-strength
      testing revealed no difference in tibialis anterior strength between the operated
      and contralateral extremity. All patients visually demonstrated postoperative
      elevation of the medial longitudinal arch height. Complications included 2 feet
      with wound dehiscence and 1 foot with fractured hardware. The results of this
      review indicate that the modified Kidner-Cobb procedure is a useful treatment
      option for patients with symptomatic flexible flatfoot with posterior tibial
      tendon dysfunction stage 2.

PMID- 20797584
TI  - Nail puncture wound through a rubber-soled shoe: a retrospective study of 96
      adult patients.
AB  - Nail punctures through rubber-soled shoes expose the foot to the possibility of
      deep infection and foreign body retention. In this article, we describe
      characteristics of adult patients who sustained nail puncture wounds through a
      rubber-soled shoe and were treated at our institution from January 1, 2000, to
      January 8, 2008. Of the 96 patients, 36 (37.5%) were treated conservatively and
      60 (62.5%) were treated surgically in the operating room. Of those treated
      surgically, 15 (25%) had a foreign body extracted during the operation. The
      operated group had a longer duration of time from injury to hospital admission
      than did the nonoperated group (5.0 +/- 6.8 days versus 2.7 +/- 3.8 days, P <
      .05). Treatment success was observed in 91 (94.8%) of the patients, and the
      median lag time before admission for the less successfully treated group was
      longer than that for the successfully treated group (10 days versus 2 days, P <
      .002); and, the less successfully treated group was more likely to receive
      antibiotics in the community before hospitalization (100.0% versus 47.2%, P <
      .06), and was more likely to be diabetic (40.0% versus 9.9%, P < .10). Fever,
      white blood cell count, and erythrocyte sedimentation rate were not significantly
      associated with treatment outcome. Success of the treatment did not depend on
      white blood cell count, erythrocyte sedimentation rate, or fever. Ultrasonography
      was useful in detecting the presence of a foreign body.

PMID- 20797585
TI  - Treatment of clubfoot with the Ponseti method: should we begin casting in the
      newborn period or later?
AB  - The Ponseti method has become accepted worldwide as the treatment of choice for
      nonoperative management of clubfoot. However, there has been no research on
      whether casting should begin in the newborn period (< or = 30 days old) or later
      (> 30 days but < 1 year old) or on whether the length of the foot at the
      beginning of casting is predictive of the outcome of therapy. Therefore, we
      conducted an investigation to compare outcomes in patients started on casting
      therapy in the newborn period or later. Outcomes were based on Pirani and
      Dimeglio scores. The study population was comprised of 40 clubfeet in 29
      consecutive infants with no associated neuromuscular disease, who underwent
      Ponseti treatment. The median follow-up was 34 months (range, 20-47 months).
      Casting began in the newborn period on 26 feet of 18 patients (newborn group),
      and after 1 month of age on 14 feet of 11 patients (older infant group). Final
      Dimeglio scores were significantly worse for the patients whose casts were
      applied in the newborn period, compared with those who had the first cast applied
      at a time >30 days postpartum (P = .04). Infants with feet > or =8 cm in length
      at the start of cast treatment had better final Dimeglio scores than those with
      feet <8 cm. Our findings suggest that casting according to the Ponseti method
      should begin in infants older than 1 month of age, or with an involved foot > or
      =8 cm in length.

PMID- 20797586
TI  - Biomechanical evaluation of acellular collagen matrix augmented Achilles tendon
      repair in sheep.
AB  - The rate of rerupture of repaired Achilles tendon in young and athletic
      populations remains high despite improvement in surgical techniques, suture
      design, and postsurgical management. Acellular biological matrices can be used to
      enhance the immediate strength of repaired tendons and to serve as scaffolds for
      cell in-growth and constructive tissue remodeling. A number of commercially
      available matrices have been used clinically, albeit with varying degrees of
      success and failure. The disparity is likely attributable to the different
      physical and biochemical properties of individual matrices. In this study, we
      investigated the biomechanical characteristics of 2 different acellular collagen
      matrices, namely TissueMend and GraftJacket, using a sheep Achilles tendon repair
      model. Static and cyclic creep, cyclic and linear construct stiffness, maximum
      load to failure, and displacement at maximum load were determined at time zero.
      We found that the maximum load to failure, displacement, and ultimate failure
      mode were similar between tendons augmented with either acellular collagen
      matrix; however, TissueMend augmentation yielded lower creep and smaller
      construct elongation than did GraftJacket. The results indicated that the
      strength of TissueMend-augmented tendons and GraftJacket-augmented tendons was
      not statistically significantly different, although tendons augmented with
      TissueMend displayed greater stiffness, which may be clinically advantageous in
      the restoration of ruptured tendons.

PMID- 20797587
TI  - Lower extremity changes experienced during pregnancy.
AB  - The anatomic and physiologic changes occurring with pregnancy result in a variety
      of symptoms affecting the lower extremity. The purpose of this investigation is
      to provide a comprehensive look at the lower extremity changes experienced during
      pregnancy and correlate symptoms with underlying etiology in a literature review.
      In this retrospective study, 100 postpartum women were interviewed regarding the
      lower extremity changes experienced in pregnancy. The interview included
      dermatologic, vascular, neurologic, and musculoskeletal portions. Results
      demonstrate more than 50% of women reported faster toenail growth, roughened
      toenail texture, increased dryness of the skin, swelling of the foot, ankle, and
      leg, unsteady gait, increased foot width, and hip pain. Though a majority of
      patients did not experience the remaining symptoms represented in the interview,
      all results are pertinent and deserve understanding to provide better insight and
      care for the pregnant woman. Therefore, a thorough literature review is presented
      to correlate the outcomes of the present study with previously published
      research.

PMID- 20797588
TI  - The need for surgical revision after isolated cheilectomy for hallux rigidus: a
      systematic review.
AB  - Isolated cheilectomy has been proposed for treatment of hallux rigidus due to the
      perceived safety, efficacy, and ability to revise with repeat cheilectomy,
      implant or interpositional arthroplasty, or arthrodesis. A systematic review was
      undertaken to better understand the need for surgical revision after isolated
      cheilectomy for hallux rigidus. Studies were eligible for inclusion only if they
      involved consecutively enrolled patients undergoing isolated cheilectomy or
      involved revision surgery of the first metatarsophalangeal joint after isolated
      cheilectomy, evaluated patients at mean follow-up > or = 12 months' duration, and
      included details of complications. Twenty-three studies, describing 706
      cheilectomies, met the inclusion criteria, with 62 (8.8%) undergoing surgical
      revision in the form of arthrodesis (n = 23), no mention of revision procedure (n
      = 17), interpositional arthroplasty (n = 13), silicone implant arthroplasty (n =
      4), Keller resection arthroplasty (n = 3), or repeat cheilectomy (n = 2). Twelve
      studies specified the grade of hallux rigidus as: 103 (19.9%) grade 1, 210
      (40.6%) grade II, 189 (36.6%) grade III, and 15 (2.9%) grade IV. Six studies
      indicated the number of cheilectomies that required revision surgery as: 2 (20%)
      grade I, 8 (14.8%) grade II, 12 (9.1%) grade III, and 5 (55.6%) grade IV. These
      results make clear the low incidence of revision surgery after cheilectomy for
      hallux rigidus. Therefore, cheilectomy should be considered a first-line surgical
      treatment for hallux rigidus. There remains a need for methodologically sound
      prospective cohort studies that focus on the use of cheilectomy for specific
      grades of hallux rigidus.

PMID- 20797589
TI  - An unusual etiology for adult-acquired flatfoot.
AB  - Rupture of the tibialis posterior tendon is widely believed to result from trauma
      in the presence of preexisting degenerative changes. We report a case of adult
      acquired flatfoot in an otherwise healthy 19-year-old man who sustained a
      fracture of the medial malleolus.

PMID- 20797590
TI  - Surgical repair of abductor hallucis muscle herniation: a case report.
AB  - Herniation of the abductor hallucis muscle has rarely been reported in the
      literature. This condition causes localized pain, especially while weight
      bearing, as a result of a complex cascade of biomechanical events directly
      related to loss of integrity of the medial wall of the foot. The authors present
      a case of a flexor retinaculum tear with subsequent herniation of the abductor
      hallucis muscle. When conservative treatment options failed to provide
      significant relief, surgical intervention was performed, which revealed ischemic
      muscle tissue and a partial flexor retinaculum tear. The nonviable muscle was
      surgically debrided and the fascial defect was repaired with a polypropylene
      nonabsorbable synthetic surgical mesh. This herniorrhaphy reestablished medial
      compartment support, thus allowing the patient to return to pain-free ambulation.

PMID- 20797591
TI  - High fibular fracture in association with triplane fracture: reexamining this
      unique pediatric fracture pattern.
AB  - A case of a high fibular fracture in association with a triplane fracture in a 12
      year-old boy is presented and this unique fracture pattern examined. Whether from
      blunt trauma or an external rotation mechanism, it appears that trans-syndesmotic
      fixation is not needed to satisfactorily repair this injury. Because of the
      rarity of the condition, there is limited previously published information
      describing this particular injury, although surgeons should be aware of it and
      the underlying mechanism of the fracture.

PMID- 20797592
TI  - Interference screw fixation and short harvest using flexor digitorum longus (FDL)
      transfer for posterior tibial tendon dysfunction: a technique.
AB  - Posterior tibial tendon dysfunction is a common clinical entity treated by foot
      and ankle specialists, and numerous surgical treatments are available to the
      modern foot and ankle surgeon. Fixation methods are constantly evolving as new
      products are developed and new uses for existing products are attempted.
      Interference screw fixation is the gold standard fixation for tendon autograft
      and allograft in orthopedic sports medicine. The technique that we describe in
      this article uses a less extensive harvest of the flexor digitorum longus tendon
      and a sound fixation method using an interference screw positioned in the tarsal
      navicular.

PMID- 20797593
TI  - Addition of a second LV pacing site in CRT nonresponders rationale and design of
      the multicenter randomized V(3) trial.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is an effective treatment of
      heart failure (HF) in presence of a depressed left ventricular (LV) ejection
      fraction and a wide QRS complex. It is limited by a high proportion of
      nonresponders. Attempts have been made, in small studies, to increase the number
      of stimulation sites to optimize the resynchronization therapy. V(3) is a planned
      multicenter, randomized trial whose objective is to evaluate the clinical benefit
      conferred by the addition of a second LV lead in nonresponders after at least 6
      months of standard biventricular stimulation. METHODS AND RESULTS: A total of 84
      patients will be enrolled in 11 French medical centers. Patients will be randomly
      assigned to receive either an additional LV lead (test group) or to keep their
      current stimulation system unchanged (control group). Enrollment is planned to
      begin in March 2010 and is expected to end within 1 year. The primary study end
      point will be the HF clinical composite score evaluated at 1 year follow-up.
      Secondary end points include degree of echocardiographic reverse remodeling and
      changes in clinical measurements. CONCLUSIONS: The V(3) trial will examine the
      clinical benefit conferred by the addition of a second LV lead in nonresponders
      to standard CRT.

PMID- 20797594
TI  - The effects of adenosine A(1) receptor antagonism in patients with acute
      decompensated heart failure and worsening renal function: the REACH UP study.
AB  - BACKGROUND: Worsening renal function (WRF) portends a poor prognosis, and recent
      deterioration in creatinine might identify patients with elevated intrarenal
      adenosine in whom adenosine A(1) antagonism may improve renal hemodynamics and
      function. The purpose of this pilot study was to assess whether rolofylline, an
      adenosine A(1) antagonist (A(1)RA), would facilitate diuresis while maintaining
      renal function in patients with acutely decompensated heart failure (ADHF) and
      recent WRF. METHODS AND RESULTS: Seventy-six patients with ADHF, volume overload,
      and recent renal deterioration received rolofylline (30 mg, n = 36) or placebo (n
      = 40) for 3 days. Rolofylline did not demonstrate a beneficial effect on the
      primary end points of worsening heart failure or renal function after admission
      or death or readmission within 30 days. Similar proportions of patients receiving
      rolofylline (33%) and placebo (30%) were treatment failures within 30 days.
      However, persistent renal impairment (through Day 14) tended to be less common
      with rolofylline (6%) than placebo (18%). At Day 14, 11 patients receiving
      placebo and 13 patients receiving rolofylline had a decrease in creatinine > or =
      0.3 mg/dL. There were fewer heart failure readmissions with rolofylline (n = 2)
      than with placebo (n = 7) through Day 60. CONCLUSIONS: The Placebo-Controlled
      Study of the Effects of KW-3902 Injectable Emulsion on Heart Failure Signs and
      Symptoms, Diuresis, Renal Function, and Clinical Outcomes in Subjects
      Hospitalized with Worsening Renal Function and Heart Failure Requiring
      Intravenous Therapy (ie, REACH UP) study did not demonstrate any clear benefit of
      rolofylline in patients with ADHF and worsening renal function. However,
      beneficial trends raise the possibility that A(1)RAs might prevent renal
      dysfunction in these high risk patients. To test this hypothesis, further larger
      studies need to evaluate the effects of adenosine A(1) antagonists in patients
      with progressive renal dysfunction in the face of active heart failure therapy.

PMID- 20797595
TI  - Acute effects of intravenous nesiritide on cardiac contractility in heart
      failure.
AB  - BACKGROUND: Although nesiritide is a potent vasodilator, studies using myocytes
      and isolated muscle strips have shown that recombinant B-type natriuretic peptide
      (BNP; nesiritide) decreases contractility. We sought to determine whether
      nesiritide decreases contractility in heart failure patients. METHODS AND
      RESULTS: Twenty-five heart failure patients underwent left heart catheterization
      (using a pressure-volume conductance catheter) and echocardiography at baseline
      and after a 2 mcg/kg bolus and 30-minute nesiritide infusion (0.01 mcg.kg.min).
      From invasive and noninvasive measurements, left ventricular (LV) systolic
      function indices were calculated, including ejection fraction, end-systolic
      elastance (E(es); single-beat invasive and noninvasive methods) and preload
      recruitable stroke work (PRSW; noninvasive, single-beat method). The mean age was
      60 +/- 11 years, 48% were male, 56% had coronary disease, and 64% had
      hypertension. Although nesiritide did not change LV ejection fraction, it did
      decrease contractility on pressure-volume analysis. Noninvasive E(es) decreased
      from 2.6 +/- 1.6 to 2.0 +/- 1.4 mm Hg/mL (P = .02). For those with reduced
      ejection fraction, E(es) decreased by invasive (P = .006) and noninvasive (P =
      .02) methods. PRSW decreased from 76 +/- 37 to 62 +/- 28 g/cm(2) (P = .003). On
      tissue Doppler imaging, nesiritide reduced the systolic annular tissue velocity
      of the mitral annulus from 8.0 +/- 1.9 to 6.9 +/- 1.3 cm/s (P = .04).
      CONCLUSIONS: Nesiritide infusion acutely decreases derived measures of
      contractility and systolic function in patients with chronic heart failure.

PMID- 20797596
TI  - Washout rate of cardiac iodine-123 metaiodobenzylguanidine is high in chronic
      heart failure patients with central sleep apnea.
AB  - BACKGROUND: The association between sleep-disordered breathing (SDB) assessed by
      polysomnography and cardiac sympathetic nerve activity (SNA) assessed by cardiac
      iodine-123 metaiodobenzylguanidine (123I-MIBG) imaging has not been investigated
      in patients with chronic heart failure (CHF). METHODS AND RESULTS: We performed
      cardiac 123I-MIBG scintigraphy and overnight polysomnography in 59 patients with
      stable CHF. The patients were classified into the 3 groups: 19 with no or mild
      SDB (NM-SDB, apnea-hypopnea index <15); 21 with central sleep apnea (CSA), and 19
      with obstructive sleep apnea (OSA). The cardiac washout rate (WR) of 123I-MIBG
      was obtained from initial and delayed planar 123I-MIBG images. The WR was higher
      in patients with CSA (54.2 + or - 11.6%) than in those with OSA (37.9 + or -
      8.6%, P < .05) or NM-SDB (40.8 + or - 8.8%, P < .05). The WR correlated
      positively with central apnea index (rho = 0.40, P = .002). A stepwise multiple
      regression analysis selected CSA and plasma brain natriuretic peptide levels as
      independent variables associated with the WR. CONCLUSIONS: The WR was higher in
      CHF patients with CSA than in those with OSA or NM-SDB, and CSA was independently
      associated with the WR, suggesting a link of CSA to increased cardiac SNA in CHF.

PMID- 20797597
TI  - Cost-effectiveness of implantable cardioverter-defibrillators in children with
      dilated cardiomyopathy.
AB  - BACKGROUND: Implantable cardioverter-defibrillators (ICDs) improve survival and
      are cost-effective in adults with poor left ventricular function. Because of
      differences in heart failure etiology, sudden death rates, and ICD complication
      rates, these findings may not be applicable to children. METHODS AND RESULTS: We
      developed a Markov model to compare typical management of childhood dilated
      cardiomyopathy with symptomatic heart failure to prophylactic ICD implantation
      plus typical management. Model costs included costs of outpatient care,
      medications, complications, and transplantation. Time horizon was up to 20 years
      from model entry. Total costs were $433,000 (ICD strategy) and $355,000 (typical
      management). Although quality adjusted survival was greater in the ICD group
      (6.78 versus 6.43 quality adjusted life-years [QALY]), the incremental cost
      utility ratio was $281,622/QALY saved with the ICD strategy. In sensitivity
      analyses, the ICD strategy cost less than the $100,000/QALY benchmark for cost
      effectiveness only when the annual probability of sudden death exceeded 13% or
      when strong, sustained benefits in quality of life from the ICD were assumed.
      CONCLUSIONS: Prophylactic ICD use in children with dilated cardiomyopathy, poor
      ventricular function, and symptomatic heart failure does not appear to be cost
      effective. This is likely due to lower sudden death rates in this population.

PMID- 20797598
TI  - Yoga in heart failure patients: a pilot study.
AB  - BACKGROUND: Complementary therapies such as yoga practice have become
      commonplace, yet the safety, physical, and psychological effects on patients with
      heart failure (HF) are unknown. The purpose of this study was to determine
      whether an 8-week yoga program was safe and would positively influence physical
      and psychological function in HF patients. METHODS AND RESULTS: Stable HF
      patients were recruited (n = 15) and completed (n = 12) 8 weeks of yoga classes.
      Data collected were: safety (cardiac and orthopedic adverse events); physical
      function (strength, balance, endurance, flexibility); and psychological function
      (quality of life [QOL], depression scores, mindfulness) before and after 8 weeks
      of yoga classes. RESULTS: Mean age was 52.4 + or - 11.6 with three-fourths (n =
      9) being male and Caucasian. No participant had any adverse events. Endurance (P
      < .02) and strength (upper P = .04 and lower body P = .01) significantly
      improved. Balance improved by 13.6 seconds (26.9 + or - 19.7 to 40.0 + or - 18.5;
      P = .05). Symptom stability, a subscale of QOL, improved significantly (P = .02).
      Although no subject was depressed, overall mood was improved. Subjects
      subjectively reported improvements in overall well-being. CONCLUSIONS: Yoga
      practice was safe, with participants experiencing improved physical function and
      symptom stability. Larger studies are warranted to provide more
      nonpharmacological options for improved outcomes in patients with HF.

PMID- 20797599
TI  - Memory dysfunction, psychomotor slowing, and decreased executive function predict
      mortality in patients with heart failure and low ejection fraction.
AB  - BACKGROUND: The purpose of this study was to evaluate whether dysfunction of
      specific cognitive abilities is a predictor of impending mortality in adults with
      systolic heart failure (HF). METHODS: A total of 166 stable outpatients with HF
      completed cognitive function evaluation in language, working memory, memory,
      visuospatial ability, psychomotor speed, and executive function using a
      neuropsychological test battery. Demographic and clinical variables, comorbidity,
      depressive symptoms, and health-related quality of life were also measured.
      Patients were followed for 12 months to determine all-cause mortality. RESULTS:
      There were 145 survivors and 21 deaths. In logistic regression analyses,
      significant predictors of mortality were lower left ventricular ejection fraction
      (LVEF) and poorer scores on measures of global congnitive function Mini-Mental
      State Examination [MMSE], working memory, memory, psychomotor speed, and
      executive function. Memory loss was the most predictive cognitive function
      variable (overall chi(2) = 17.97, df = 2, P < .001; Nagelkerke R(2) = 0.20).
      Gender was a significant covariate in 2 models, with men more likely to die. Age,
      comorbidity, depressive symptoms, and health-related quality of life were not
      significant predictors. In further analyses, significant predictors of mortality
      were lower systolic blood pressure and poorer global cognitive function, working
      memory, memory, psychomotor speed, and executive function, with memory being the
      most predictive. CONCLUSIONS: As hypothesized, lower LVEF and memory dysfunction
      predicted mortality. Poorer global cognitive score as determined by the MMSE,
      working memory, psychomotor speed, and executive function were also significant
      predictors. LVEF or systolic blood pressure had similar predictive values.
      Interventions are urgently needed to prevent and manage memory loss in HF.

PMID- 20797600
TI  - Impaired glucose tolerance and insulin resistance in heart failure:
      underrecognized and undertreated?
AB  - BACKGROUND: A link between diabetes mellitus (DM) and heart failure (HF) has been
      well-recognized for more than a century. HF is also closely linked to abnormal
      glucose regulation (AGR) and insulin resistance (IR) in patients without DM and,
      similarly, these conditions commonly coexist. In epidemiological studies, each
      condition appears to predict the other. The prevalence of AGR/IR in HF patients
      without DM is significantly underrecognized and, as yet, the optimal method for
      screening for these abnormalities in the outpatient setting is unclear. METHODS
      AND RESULTS: The purpose of this review is to overview the prevalence and
      prognostic impact of AGR and IR in HF patients without DM and discuss potential
      pathophysiological pathways that link these conditions with HF. The severity of
      glucose intolerance in patients with HF correlates with functional and clinical
      severity of HF and is an independent predictor of an adverse outcome. It is
      thought that changes in cardiac metabolism, including a switch from glucose
      metabolism toward fatty acid metabolism, may in part contribute to the
      pathophysiological processes associated with HF patients with AGR/IR.
      CONCLUSIONS: We discuss how pharmacological targeting of metabolic pathways in
      the myocardium of these patients with HF may represent novel therapeutic
      strategies in these at-risk patients.

PMID- 20797601
TI  - Mast cell stabilization decreases cardiomyocyte and LV function in dogs with
      isolated mitral regurgitation.
AB  - BACKGROUND: Mast cells are increased in isolated mitral regurgitation (MR) in the
      dog and may mediate extracellular matrix loss and left ventricular (LV)
      dilatation. We tested the hypothesis that mast cell stabilization would attenuate
      LV remodeling and improve function in the MR dog. METHODS AND RESULTS: MR was
      induced in adult dogs randomized to no treatment (MR, n = 5) or to the mast cell
      stabilizer, ketotifen (MR + MCS, n = 4) for 4 months. LV hemodynamics were
      obtained at baseline and after 4 months of MR and magnetic resonance imaging
      (MRI) was performed at sacrifice. MRI-derived, serial, short-axis LV end
      diastolic (ED) and end-systolic (ES) volumes, LVED volume/mass ratio, and LV 3
      dimensional radius/wall thickness were increased in MR and MR + MCS dogs compared
      with normal dogs (n = 6) (P < .05). Interstitial collagen was decreased by 30% in
      both MR and MR + MCS versus normal dogs (P < .05). LV contractility by LV maximum
      time-varying elastance was significantly depressed in MR and MR + MCS dogs.
      Furthermore, cardiomyocyte fractional shortening was decreased in MR versus
      normal dogs and further depressed in MR + MCS dogs (P < .05). In vitro
      administration of ketotifen to normal cardiomyocytes also significantly decreased
      fractional shortening and calcium transients. CONCLUSIONS: Chronic mast cell
      stabilization did not attenuate eccentric LV remodeling or collagen loss in MR.
      However, MCS therapy had a detrimental effect on LV function because of a direct
      negative inotropic effect on cardiomyocyte function.

PMID- 20797604
TI  - Chasing HIV from its hiding place.

PMID- 20797603
TI  - Myocardial function with reduced expression of the sodium-calcium exchanger.
AB  - BACKGROUND: The complete removal of the cardiac sodium-calcium exchanger (NCX1)
      is associated with embryonic lethality, whereas its overexpression is linked to
      heart failure. To determine whether or not a reduced expression of NCX1 is
      compatible with normal heart structure and function, we studied 2 knockout (KO)
      mouse models with reduced levels of NCX1: a heterozygous global KO (HG-KO) with a
      50% level of NCX1 expression in all myocytes, and a ventricular-specific KO (V
      KO) with NCX1 expression in only 10% to 20% of the myocytes. METHODS AND RESULTS:
      Both groups of mice were evaluated at baseline, after transaortic constriction
      (TAC), and after acute or chronic beta-adrenergic stimulation. At baseline, the
      HG-KO mice had smaller hearts and the V-KO mice had larger hearts than their wild
      type (WT) controls (P < .05). The HG-KO and their control WT mice had normal
      responses to TAC and beta-adrenergic stimulation. However, the V-KO group was
      intolerant to TAC and had a significantly (P < .05) blunted response to beta
      adrenergic stimulation as compared with the HG-KO mice and WT controls. Unlike
      the HG-KO mice, the V-KO mice did not tolerate chronic isoproterenol infusion.
      Telemetric analysis of the electrocardiogram, body temperature, and activity
      revealed a normal diurnal rhythm in all groups of mice, but confirmed shorter QT
      intervals along with increased arrhythmias and reduced R wave to P wave amplitude
      ratios in the V-KO mice. CONCLUSIONS: Though NCX1 can be reduced by half in all
      myocytes without significant functional alterations, it must be expressed in more
      than 20% of the myocytes to prevent severe remodeling and heart failure in mouse
      heart.

PMID- 20797602
TI  - Effects of ACE2 inhibition in the post-myocardial infarction heart.
AB  - BACKGROUND: There is evidence that angiotensin-converting enzyme 2 (ACE2) is
      cardioprotective. To assess this in the post-myocardial infarction (MI) heart, we
      treated adult male Sprague-Dawley rats with either placebo (PL) or C16, a
      selective ACE2 inhibitor, after permanent coronary artery ligation or sham
      operation. METHODS AND RESULTS: Coronary artery ligation resulting in MI between
      25% to 50% of the left ventricular (LV) circumference caused substantial cardiac
      remodeling. Daily C16 administration from postoperative days 2 to 28 at a dose
      that inhibited myocardial ACE2 activity was associated with a significant
      increase in MI size and reduction in LV % fractional shortening. Treatment with
      C16 did not significantly affect post-MI increases in LV end-diastolic dimension
      but did inhibit increases in wall thickness and fibrosis in non-infarcted LV. On
      postoperative day 7, C16 had no significant effect on the increased level of
      apoptosis in the infarct and border zones nor did it significantly affect
      capillary density surrounding the MI. It did, however, significantly reduce the
      number of c-kit(+) cells in the border region. CONCLUSIONS: These findings
      support the notion that ACE2 exerts cardioprotective effects by preserving
      jeopardized cardiomyocytes in the border zone. The reduction in hypertrophy and
      fibrosis with C16, however, suggests that ACE2 activity has diverse effects on
      post-MI remodeling.

PMID- 20797605
TI  - The awesome power of synergy from chemical-chemical profiling.
AB  - Chemical-chemical profiling, as described in Farha and Brown (2010), delivers all
      the power of chemical-genomic profiling while untethering researchers from model
      systems and thereby enabling us to pursue cell-based drug target identification
      in almost any organism.

PMID- 20797606
TI  - Adding the lipo to lipopeptides: do more with less.
AB  - Surfactin is a member of the lipopeptide family of antibiotics, which includes
      the clinical drug daptomycin (Cubicin). The potency of these antibiotics is
      affected by the attached lipid chain, which is incorporated into the
      nonribosomally assembled peptidyl backbone via a process known as lipoinitiation.
      Kraas et al. (2010) have provided valuable insights into the lipoinitiation
      mechanism, which will be useful for future biosynthetic modifications of
      lipopeptide antibiotics.

PMID- 20797607
TI  - Expanding the biological periodic table.
AB  - Metal ions play an indispensable role in biology, enabling enzymes to perform
      their functions and lending support to the structures of numerous macromolecules.
      Despite their prevalence and importance, the metalloproteome is still relatively
      unexplored. Cvetkovic et al. (2010) now describe an approach to identify
      metalloproteins on a genome-wide scale.

PMID- 20797608
TI  - Activity-based profiling reveals reactivity of the murine thymoproteasome
      specific subunit beta5t.
AB  - Epithelial cells of the thymus cortex express a unique proteasome particle
      involved in positive T cell selection. This thymoproteasome contains the recently
      discovered beta5t subunit that has an uncharted activity, if any. We synthesized
      fluorescent epoxomicin probes that were used in a chemical proteomics approach,
      entailing activity-based profiling, affinity purification, and LC-MS
      identification, to demonstrate that the beta5t subunit is catalytically active in
      the murine thymus. A panel of established proteasome inhibitors showed that the
      broad-spectrum inhibitor epoxomicin blocks the beta5t activity and that the
      subunit-specific antagonists bortezomib and NC005 do not inhibit beta5t. We show
      that beta5t has a substrate preference distinct from beta5/beta5i that might
      explain how the thymoproteasome generates the MHC class I peptide repertoire
      needed for positive T cell selection.

PMID- 20797609
TI  - Two molecules of lobophorolide cooperate to stabilize an actin dimer using both
      their "ring" and "tail" region.
AB  - Actin filament-disrupting marine macrolides are promising templates from which to
      design therapeutics against cancer and other diseases that co-opt the actin
      cytoskeleton. Typically, these macrolides form either a 1:1 or 2:1 actin
      macrolide complex where their aliphatic side chain, or "tail," has been reported
      to convey the major determinant of cytotoxicity. We now report the structure of
      the marine macrolide lobophorolide bound to actin with a unique 2:2 stoichiometry
      in which two lobophorolide molecules cooperate to form a dimerization interface
      that is composed entirely of the macrolide "ring" region, and each molecule of
      lobophorolide interacts with both actin subunits via their ring and tail regions
      to tether the subunits together. This binding mode imposes multiple barriers
      against microfilament stability and holds important implications for development
      of actin-targeting drugs and the evolution of macrolide biosynthetic enzymes.

PMID- 20797610
TI  - Functional studies of Plasmodium falciparum dipeptidyl aminopeptidase I using
      small molecule inhibitors and active site probes.
AB  - The widespread resistance of malaria parasites to all affordable drugs has made
      the identification of new targets urgent. Dipeptidyl aminopeptidases (DPAPs)
      represent potentially valuable new targets that are involved in hemoglobin
      degradation (DPAP1) and parasite egress (DPAP3). Here we use activity-based
      probes to demonstrate that specific inhibition of DPAP1 by a small molecule
      results in the formation of an immature trophozoite that leads to parasite death.
      Using computational methods, we designed stable, nonpeptidic covalent inhibitors
      that kill Plasmodium falciparum at low nanomolar concentrations. These compounds
      show signs of slowing parasite growth in a murine model of malaria, which
      suggests that DPAP1 might be a viable antimalarial target. Interestingly, we
      found that resynthesis and activation of DPAP1 after inhibition is rapid,
      suggesting that effective drugs would need to sustain DPAP1 inhibition for a
      period of 2-3 hr.

PMID- 20797611
TI  - A metabolomic view of Staphylococcus aureus and its ser/thr kinase and
      phosphatase deletion mutants: involvement in cell wall biosynthesis.
AB  - Little is known about intracellular metabolite pools in pathogens such as
      Staphylococcus aureus. We have studied a particular metabolome by means of the
      presented LC-MS method. By investigating the central carbon metabolism which
      includes most of the energy transfer molecules like nucleotides, sugar mono- and
      biphosphates, and cofactors, a conclusion about phenotypes and stress answers in
      microorganisms is possible. Quantitative metabolite levels of S. aureus grown in
      complex lysogeny broth and in minimal medium were compared in the wild-type S.
      aureus strain 8325 and the isogenic eukaryotic-like protein serine/threonine
      kinase (DeltapknB) and phosphatase (Deltastp) deletion mutants. Detection of
      several remarkable differences, e.g., in nucleotide metabolism and especially
      cell wall precursor metabolites, indicates a previously unreported importance of
      serine/threonine kinase/phosphatase on peptidoglycan and wall teichoic acid
      biosynthesis. These findings may lead to new insights into the regulation of
      staphylococcal cell wall metabolism.

PMID- 20797612
TI  - The glycerophospho metabolome and its influence on amino acid homeostasis
      revealed by brain metabolomics of GDE1(-/-) mice.
AB  - GDE1 is a mammalian glycerophosphodiesterase (GDE) implicated by in vitro studies
      in the regulation of glycerophophoinositol (GroPIns) and possibly other
      glycerophospho (GroP) metabolites. Here, we show using untargeted metabolomics
      that GroPIns is profoundly (>20-fold) elevated in brain tissue from GDE1(-/-)
      mice. Furthermore, two additional GroP metabolites not previously identified in
      eukaryotic cells, glycerophosphoserine (GroPSer) and glycerophosphoglycerate
      (GroPGate), were also highly elevated in GDE1(-/-) brains. Enzyme assays with
      synthetic GroP metabolites confirmed that GroPSer and GroPGate are direct
      substrates of GDE1. Interestingly, our metabolomic profiles also revealed that
      serine (both L-and D-) levels were significantly reduced in brains of GDE1(-/-)
      mice. These findings designate GroPSer as a previously unappreciated reservoir
      for free serine in the nervous system and suggest that GDE1, through recycling
      serine from GroPSer, may impact D-serine-dependent neural signaling processes in
      vivo.

PMID- 20797614
TI  - Chemical probes of Escherichia coli uncovered through chemical-chemical
      interaction profiling with compounds of known biological activity.
AB  - While cell-based screens have considerable power in identifying new chemical
      probes of biological systems and leads for new drugs, a major challenge to the
      utility of such compounds is in connecting phenotype with a cellular target.
      Here, we present a systematic study to elucidate the mechanism of action of
      uncharacterized inhibitors of the growth of Escherichia coli through careful
      analyses of interactions with compounds of known biological activity. We studied
      growth inhibition with a collection of 200 antibacterial compounds when
      systematically combined with a panel of 14 known antibiotics of diverse mechanism
      and chemical class. Our work revealed a high frequency of synergistic chemical
      chemical interactions where the interaction profiles were unique to the various
      compound pairs. Thus, the work revealed that chemical-chemical interaction data
      provides a fingerprint of biological activity and testable hypotheses regarding
      the mechanism of action of the novel bioactive molecules. In the study reported
      here, we determined the mode of action of an inhibitor of folate biosynthesis and
      a DNA gyrase inhibitor. Moreover, we identified eight membrane-active compounds,
      found to be promiscuously synergistic with known bioactives.

PMID- 20797613
TI  - Structure of cytochrome P450 PimD suggests epoxidation of the polyene macrolide
      pimaricin occurs via a hydroperoxoferric intermediate.
AB  - We present the X-ray structure of PimD, both substrate-free and in complex with
      4,5-desepoxypimaricin. PimD is a cytochrome P450 monooxygenase with native
      epoxidase activity that is critical in the biosynthesis of the polyene macrolide
      antibiotic pimaricin. Intervention in this secondary metabolic pathway could
      advance the development of drugs with improved pharmacologic properties.
      Epoxidation by P450 typically includes formation of a charge-transfer complex
      between an oxoferryl pi-cation radical species (Compound I) and the olefin pi
      bond as the initial intermediate. Catalytic and structural evidence presented
      here suggest that epoxidation of 4,5-desepoxypimaricin proceeds via a
      hydroperoxoferric intermediate (Compound 0). The oxygen atom of Compound 0 distal
      to the heme iron may insert into the double bond of the substrate to make an
      epoxide ring. Stereoelectronic features of the putative transition state suggest
      substrate-assisted proton delivery.

PMID- 20797615
TI  - Switching from an esterase to a hydroxynitrile lyase mechanism requires only two
      amino acid substitutions.
AB  - The alpha/beta hydrolase superfamily contains mainly esterases, which catalyze
      hydrolysis, but also includes hydroxynitrile lyases, which catalyze addition of
      cyanide to aldehydes, a carbon-carbon bond formation. Here, we convert a plant
      esterase, SABP2, into a hydroxynitrile lyase using just two amino acid
      substitutions. Variant SABP2-G12T-M239K lost the ability to catalyze ester
      hydrolysis (<0.9 mU/mg) and gained the ability to catalyze the release of cyanide
      from mandelonitrile (20 mU/mg, k(cat)/K(M) = 70 min(-1)M(-1)). This variant also
      catalyzed the reverse reaction, formation of mandelonitrile with low
      enantioselectivity: 20% ee (S), E = 1.5. The specificity constant for the lysis
      of mandelontrile is 13,000-fold faster than the uncatalyzed reaction and only
      1300-fold less efficient (k(cat/)K(M)) than hydroxynitrile lyase from rubber
      tree.

PMID- 20797616
TI  - Functional dissection of surfactin synthetase initiation module reveals insights
      into the mechanism of lipoinitiation.
AB  - Although the N-terminally attached fatty acids are key structural elements of
      nonribosomally assembled lipopeptide antibiotics, little is known about the
      mechanism of lipid transfer during the initial step of biosynthesis. In this
      study, we investigated the activity of the dissected initiation module (C-A(Glu)
      PCP) of surfactin synthetase SrfAA in vitro to gain further insights into the
      lipoinitiation reaction. The dissected condensation (C) domain catalyzes the
      transfer of CoA-activated 3-hydroxy fatty acid with high substrate specificity at
      its donor site to the peptidyl carrier protein (PCP) bound amino acid glutamate
      (Glu(1)). Additionally, biochemical studies on four putative acyl CoA ligases in
      Bacillus subtilis revealed that two of them activate 3-hydroxy fatty acids for
      surfactin biosynthesis in vitro and that the disruption of corresponding genes
      has a significant influence on surfactin production.

PMID- 20797617
TI  - Application of fragment-based drug discovery to membrane proteins: identification
      of ligands of the integral membrane enzyme DsbB.
AB  - Membrane proteins are important pharmaceutical targets, but they pose significant
      challenges for fragment-based drug discovery approaches. Here, we present the
      first successful use of biophysical methods to screen for fragment ligands to an
      integral membrane protein. The Escherichia coli inner membrane protein DsbB was
      solubilized in detergent micelles and lipid bilayer nanodiscs. The solubilized
      protein was immobilized with retention of functionality and used to screen 1071
      drug fragments for binding using target immobilized NMR Screening. Biochemical
      and biophysical validation of the eight most potent hits revealed an IC(50) range
      of 7-200 microM. The ability to insert a broad array of membrane proteins into
      nanodiscs, combined with the efficiency of TINS, demonstrates the feasibility of
      finding fragments targeting membrane proteins.

PMID- 20797618
TI  - Modulation of pantothenate kinase 3 activity by small molecules that interact
      with the substrate/allosteric regulatory domain.
AB  - Pantothenate kinase (PanK) catalyzes the rate-controlling step in coenzyme A
      (CoA) biosynthesis. PanK3 is stringently regulated by acetyl-CoA and uses an
      ordered kinetic mechanism with ATP as the leading substrate. Biochemical analysis
      of site-directed mutants indicates that pantothenate binds in a tunnel adjacent
      to the active site that is occupied by the pantothenate moiety of the acetyl-CoA
      regulator in the PanK3acetyl-CoA binary complex. A high-throughput screen for
      PanK3 inhibitors and activators was applied to a bioactive compound library.
      Thiazolidinediones, sulfonylureas and steroids were inhibitors, and fatty acyl
      amides and tamoxifen were activators. The PanK3 activators and inhibitors either
      stimulated or repressed CoA biosynthesis in HepG2/C3A cells. The flexible
      allosteric acetyl-CoA regulatory domain of PanK3 also binds the substrates,
      pantothenate and pantetheine, and small molecule inhibitors and activators to
      modulate PanK3 activity.

PMID- 20797619
TI  - Nitric oxide-mediated histone hyperacetylation in oral cancer: target for a water
      soluble HAT inhibitor, CTK7A.
AB  - Altered histone acetylation is associated with several diseases, including
      cancer. We report here that, unlike in most cancers, histones are found to be
      highly hyperacetylated in oral squamous cell carcinoma (OSCC; oral cancer)
      patient samples. Mechanistically, overexpression, as well as enhanced
      autoacetylation, of p300 induced by nucleophosmin (NPM1) and glyceraldehyde 3
      phosphate dehydrogenase (GAPDH) causes the hyperacetylation, which is nitric
      oxide (NO) signal dependent. Inhibition of the histone acetyltransferase (HAT)
      activity of p300 by a water-soluble, small molecule inhibitor, Hydrazinocurcumin
      (CTK7A), substantially reduced the xenografted oral tumor growth in mice. These
      results, therefore, not only establish an epigenetic target for oral cancer, but
      also implicate a HAT inhibitor (HATi) as a potential therapeutic molecule.

PMID- 20797620
TI  - GTP: gatekeeper for autophagy.
AB  - Chaperone-mediated autophagy (CMA) is involved in cellular quality control, and
      in the response to stress, deterioration in CMA contributes to the aging
      phenotype and to various disorders. The paper by Bandyopadhyay et al. in this
      issue of Molecular Cell demonstrates the role of GTP binding by elongation factor
      1 alpha (EF1alpha) in regulating the lysosomal uptake of CMA substrates.

PMID- 20797621
TI  - Termination at sTop2.
AB  - In this issue of Molecular Cell, Fachinetti et al. provide the first
      comprehensive map of replication termination sites (TERs) in Saccharomyces
      cerevisiae (Fachinetti et al., 2010). Strikingly, the majority of TERs are
      occupied by topoisomerase 2, which shields these regions against genomic
      instability.

PMID- 20797622
TI  - Apollo-taking the lead in telomere protection.
AB  - The single-stranded overhangs at the ends of telomeres are thought to be critical
      for telomere maintenance, but how they are generated has been largely unclear.
      Two studies (one in this issue of Molecular Cell, Wu et al., 2010) have now
      implicated the Apollo nuclease in maintaining the overhang specifically at those
      telomeres generated by leading-strand DNA synthesis.

PMID- 20797624
TI  - Hsp12 is an intrinsically unstructured stress protein that folds upon membrane
      association and modulates membrane function.
AB  - Hsp12 of S. cerevisiae is upregulated several 100-fold in response to stress. Our
      phenotypic analysis showed that this protein is important for survival of a
      variety of stress conditions, including high temperature. In the absence of
      Hsp12, we observed changes in cell morphology under stress conditions.
      Surprisingly, in the cell, Hsp12 exists both as a soluble cytosolic protein and
      associated to the plasma membrane. The in vitro analysis revealed that Hsp12,
      unlike all other Hsps studied so far, is completely unfolded; however, in the
      presence of certain lipids, it adopts a helical structure. The presence of Hsp12
      does not alter the overall lipid composition of the plasma membrane but increases
      membrane stability.

PMID- 20797623
TI  - STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the
      epigenetic switch linking inflammation to cancer.
AB  - A transient inflammatory signal can initiate an epigenetic switch from
      nontransformed to cancer cells via a positive feedback loop involving NF-kappaB,
      Lin28, let-7, and IL-6. We identify differentially regulated microRNAs important
      for this switch and putative transcription factor binding sites in their
      promoters. STAT3, a transcription factor activated by IL-6, directly activates
      miR-21 and miR-181b-1. Remarkably, transient expression of either microRNA
      induces the epigenetic switch. MiR-21 and miR-181b-1, respectively, inhibit PTEN
      and CYLD tumor suppressors, leading to increased NF-kappaB activity required to
      maintain the transformed state. These STAT3-mediated regulatory circuits are
      required for the transformed state in diverse cell lines and tumor growth in
      xenografts, and their transcriptional signatures are observed in colon
      adenocarcinomas. Thus, STAT3 is not only a downstream target of IL-6 but, with
      miR-21, miR-181b-1, PTEN, and CYLD, is part of the positive feedback loop that
      underlies the epigenetic switch that links inflammation to cancer.

PMID- 20797625
TI  - Combined functional genomic and proteomic approaches identify a PP2A complex as a
      negative regulator of Hippo signaling.
AB  - The Hippo (Hpo) pathway is a central determinant of tissue size in both
      Drosophila and higher organisms. The core of the pathway is a kinase cascade
      composed of an upstream kinase Hpo (MST1/2 in mammals) and a downstream kinase
      Warts (Wts, Lats1/2 in mammals), as well as several scaffold proteins, Sav,
      dRASSF, and Mats. Activation of the core kinase cassette results in
      phosphorylation and inactivation of the progrowth transcriptional coactivator
      Yki, leading to increased apoptosis and reduced tissue growth. The mechanisms
      that prevent inappropriate Hpo activation remain unclear, and in particular, the
      identity of the phosphatase that antagonizes Hpo is unknown. Using combined
      proteomic and RNAi screening approaches, we identify the dSTRIPAK PP2A complex as
      a major regulator of Hpo signaling. dSTRIPAK depletion leads to increased Hpo
      activatory phosphorylation and repression of Yki target genes in vivo, suggesting
      this phosphatase complex prevents Hpo activation during development.

PMID- 20797626
TI  - Identification of regulators of chaperone-mediated autophagy.
AB  - Chaperone-mediated autophagy (CMA) is a selective mechanism for the degradation
      of cytosolic proteins in lysosomes that contributes to cellular quality control
      and becomes an additional source of amino acids when nutrients are scarce. A
      chaperone complex delivers CMA substrates to a receptor protein at the lysosomal
      membrane that assembles into multimeric translocation complexes. However, the
      mechanisms regulating this process remain, for the most part, unknown. In this
      work, we have identified two regulatory proteins, GFAP and EF1alpha, that mediate
      a previously unknown inhibitory effect of GTP on CMA. GFAP stabilizes the
      multimeric translocation complex against chaperone-mediated disassembly, whereas
      GTP-mediated release of EF1alpha from the lysosomal membrane promotes self
      association of GFAP, disassembly of the CMA translocation complex, and the
      consequent decrease in CMA. The dynamic interactions of these two proteins at the
      lysosomal membrane unveil now a role for GTP as a negative regulator of CMA.

PMID- 20797627
TI  - Catalysis of lysine 48-specific ubiquitin chain assembly by residues in E2 and
      ubiquitin.
AB  - Protein ubiquitination is catalyzed by ubiquitin-conjugating enzymes (E2s) in
      collaboration with ubiquitin-protein ligases (E3s). This process depends on
      nucleophilic attack by a substrate lysine on a thioester bond linking the C
      terminus of ubiquitin to a cysteine in the E2 active site. Different E2 family
      members display specificity for lysines in distinct contexts. We addressed the
      mechanistic basis for this lysine selectivity in Ubc1, an E2 that catalyzes the
      ubiquitination of lysine 48 (K48) in ubiquitin, leading to the formation of K48
      linked polyubiquitin chains. We identified a cluster of polar residues near the
      Ubc1 active site, as well as a residue in ubiquitin itself, that are required for
      catalysis of K48-specific ubiquitin ligation, but not for general activity toward
      other lysines. Our results suggest that the active site of Ubc1, as well as the
      surface of ubiquitin, contains specificity determinants that channel specific
      lysines to the central residues involved directly in catalysis.

PMID- 20797628
TI  - The three-dimensional organization of polyribosomes in intact human cells.
AB  - Structural studies have provided detailed insights into different functional
      states of the ribosome and its interaction with factors involved in nascent
      peptide folding, processing, and targeting. However, how the translational
      machinery is organized spatially in native cellular environments is not yet well
      understood. Here we have mapped individual ribosomes in electron tomograms of
      intact human cells by template matching and determined the average structure of
      the ribosome in situ. Characteristic features of active ribosomes in the cellular
      environment were assigned to the tRNA channel, elongation factors, and additional
      densities near the peptide tunnel. Importantly, the relative spatial
      configuration of neighboring ribosomes in the cell is clearly nonrandom. The
      preferred configurations are specific for active polysomes and were largely
      abrogated in puromycin-treated control cells. The distinct neighbor orientations
      found in situ resemble configurations of bacterial polysomes in vitro, indicating
      a conserved supramolecular organization with implications for nascent polypeptide
      folding.

PMID- 20797629
TI  - Nuclear IKKbeta is an adaptor protein for IkappaBalpha ubiquitination and
      degradation in UV-induced NF-kappaB activation.
AB  - Proinflammatory cytokines activate NF-kappaB using the IkappaB kinase (IKK)
      complex that phosphorylates inhibitory proteins (IkappaBs) at N-terminal sites
      resulting in their ubiquitination and degradation in the cytoplasm. Although
      ultraviolet (UV) irradiation does not lead to IKK activity, it activates NF
      kappaB by an unknown mechanism through IkappaBalpha degradation without N
      terminal phosphorylation. Here, we describe an adaptor function of nuclear
      IKKbeta in UV-induced IkappaBalpha degradation. UV irradiation induces the
      nuclear translocation of IkappaBalpha and association with IKKbeta, which
      constitutively interacts with beta-TrCP through heterogeneous ribonucleoprotein-U
      (hnRNP-U) leading to IkappaBalpha ubiquitination and degradation. Furthermore,
      casein kinase 2 (CK2) and p38 associate with IKKbeta and promote IkappaBalpha
      degradation by phosphorylation at C-terminal sites. Thus, nuclear IKKbeta acts as
      an adaptor protein for IkappaBalpha degradation in UV-induced NF-kappaB
      activation. NF-kappaB activated by the nuclear IKKbeta adaptor protein suppresses
      anti-apoptotic gene expression and promotes UV-induced cell death.

PMID- 20797630
TI  - RNA polymerase I contains a TFIIF-related DNA-binding subcomplex.
AB  - The eukaryotic RNA polymerases Pol I, II, and III use different promoters to
      transcribe different classes of genes. Promoter usage relies on initiation
      factors, including TFIIF and TFIIE, in the case of Pol II. Here, we show that the
      Pol I-specific subunits A49 and A34.5 form a subcomplex that binds DNA and is
      related to TFIIF and TFIIE. The N-terminal regions of A49 and A34.5 form a
      dimerization module that stimulates polymerase-intrinsic RNA cleavage and has a
      fold that resembles the TFIIF core. The C-terminal region of A49 forms a "tandem
      winged helix" (tWH) domain that binds DNA with a preference for the upstream
      promoter nontemplate strand and is predicted in TFIIE. Similar domains are
      predicted in Pol III-specific subunits. Thus, Pol I/III subunits that have no
      counterparts in Pol II are evolutionarily related to Pol II initiation factors
      and may have evolved to mediate promoter specificity and transcription
      processivity.

PMID- 20797631
TI  - Replication termination at eukaryotic chromosomes is mediated by Top2 and occurs
      at genomic loci containing pausing elements.
AB  - Chromosome replication initiates at multiple replicons and terminates when forks
      converge. In E. coli, the Tus-TER complex mediates polar fork converging at the
      terminator region, and aberrant termination events challenge chromosome integrity
      and segregation. Since in eukaryotes, termination is less characterized, we used
      budding yeast to identify the factors assisting fork fusion at replicating
      chromosomes. Using genomic and mechanistic studies, we have identified and
      characterized 71 chromosomal termination regions (TERs). TERs contain fork
      pausing elements that influence fork progression and merging. The Rrm3 DNA
      helicase assists fork progression across TERs, counteracting the accumulation of
      X-shaped structures. The Top2 DNA topoisomerase associates at TERs in S phase,
      and G2/M facilitates fork fusion and prevents DNA breaks and genome
      rearrangements at TERs. We propose that in eukaryotes, replication fork barriers,
      Rrm3, and Top2 coordinate replication fork progression and fusion at TERs, thus
      counteracting abnormal genomic transitions.

PMID- 20797632
TI  - A proteomic screen for nucleolar SUMO targets shows SUMOylation modulates the
      function of Nop5/Nop58.
AB  - Posttranslational SUMO modification is an important mechanism of regulating
      protein function, especially in the cell nucleus. The nucleolus is the subnuclear
      organelle responsible for rRNA synthesis, processing, and assembly of the large
      and small ribosome subunits. Here, we have used SILAC-based quantitative
      proteomics to identify nucleolar SUMOylated proteins. This reveals a role for
      SUMOylation in the biogenesis and/or function of small nucleolar
      ribonucleoprotein complexes (snoRNPs) via the targeting of Nhp2 and Nop58. Using
      combined in vitro and in vivo approaches, both Nhp2 and Nop58 (also known as
      Nop5) are shown to be substrates for SUMOylation. Mutational analyses revealed
      the sites of modification on Nhp2 as K5, and on Nop58 as K467 and K497. Unlike
      Nop58 and Nhp2, the closely related Nop56 and 15.5K proteins appear not to be
      SUMO targets. SUMOylation is essential for high-affinity Nop58 binding to
      snoRNAs. This study provides direct evidence linking SUMO modification with
      snoRNP function.

PMID- 20797634
TI  - Site-specific identification of SUMO-2 targets in cells reveals an inverted
      SUMOylation motif and a hydrophobic cluster SUMOylation motif.
AB  - Reversible protein modification by small ubiquitin-like modifiers (SUMOs) is
      critical for eukaryotic life. Mass spectrometry-based proteomics has proven
      effective at identifying hundreds of potential SUMO target proteins. However,
      direct identification of SUMO acceptor lysines in complex samples by mass
      spectrometry is still very challenging. We have developed a generic method for
      the identification of SUMO acceptor lysines in target proteins. We have
      identified 103 SUMO-2 acceptor lysines in endogenous target proteins. Of these
      acceptor lysines, 76 are situated in the SUMOylation consensus site [VILMFPC]KxE.
      Interestingly, eight sites fit the inverted SUMOylation consensus motif
      [ED]xK[VILFP]. In addition, we found direct mass spectrometric evidence for
      crosstalk between SUMOylation and phosphorylation with a preferred spacer between
      the SUMOylated lysine and the phosphorylated serine of four residues. In 16
      proteins we identified a hydrophobic cluster SUMOylation motif (HCSM). SUMO
      conjugation of RanGAP1 and ZBTB1 via HCSMs is remarkably efficient.

PMID- 20797633
TI  - MMXD, a TFIIH-independent XPD-MMS19 protein complex involved in chromosome
      segregation.
AB  - Xeroderma pigmentosum group D (XPD) protein is one of the subunits of TFIIH that
      is required for nucleotide excision repair and transcription. We found a XPD
      protein complex containing MMS19 that was assumed to be a regulator of TFIIH.
      However, the MMS19-XPD complex did not contain any other subunits of TFIIH.
      Instead, it included FAM96B (now designated MIP18), Ciao1, and ANT2. MMS19,
      MIP18, and XPD localized to the mitotic spindle during mitosis. The siRNA
      mediated knockdown of MMS19, MIP18, or XPD led to improper chromosome segregation
      and the accumulation of nuclei with abnormal shapes. In addition, the frequency
      of abnormal mitosis and nuclei was increased in XP-D and XP-D/CS patients' cells.
      These results indicate that the MMS19-XPD protein complex, now designated MMXD
      (MMS19-MIP18-XPD), is required for proper chromosome segregation, an abnormality
      of which could contribute to the pathogenesis in some cases of XP-D and XP-D/CS.

PMID- 20797635
TI  - Are genome-wide association studies of infection any value?

PMID- 20797636
TI  - Biosafety and tuberculosis laboratories in Africa.

PMID- 20797637
TI  - It'll be fine with a bit of ice and lemon.

PMID- 20797638
TI  - Invasive infections and sickle-cell disease.

PMID- 20797640
TI  - Cervical cancer incidence can increase despite HPV vaccination.

PMID- 20797642
TI  - Acute bacterial meningitis.

PMID- 20797643
TI  - Tuberculosis and diabetes mellitus: is vitamin D the missing link?

PMID- 20797644
TI  - Best drug treatment for multidrug-resistant and extensively drug-resistant
      tuberculosis.
AB  - Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are
      generally thought to have high mortality rates. However, many cases can be
      treated with the right combination and rational use of available antituberculosis
      drugs. This Review describes the evidence available for each drug and discusses
      the basis for recommendations for the treatment of patients with MDR and XDR
      tuberculosis. The recommended regimen is the combination of at least four drugs
      to which the Mycobacterium tuberculosis isolate is likely to be susceptible.
      Drugs are chosen with a stepwise selection process through five groups on the
      basis of efficacy, safety, and cost. Among the first group (the oral first-line
      drugs) high-dose isoniazid, pyrazinamide, and ethambutol are thought of as an
      adjunct for the treatment of MDR and XDR tuberculosis. The second group is the
      fluoroquinolones, of which the first choice is high-dose levofloxacin. The third
      group are the injectable drugs, which should be used in the following order:
      capreomycin, kanamycin, then amikacin. The fourth group are called the second
      line drugs and should be used in the following order: thioamides, cycloserine,
      then aminosalicylic acid. The fifth group includes drugs that are not very
      effective or for which there are sparse clinical data. Drugs in group five should
      be used in the following order: clofazimine, amoxicillin with clavulanate,
      linezolid, carbapenems, thioacetazone, then clarithromycin.

PMID- 20797646
TI  - Guillain-Barre syndrome after exposure to influenza virus.
AB  - Guillain-Barre syndrome (GBS) is an acute, acquired, monophasic autoimmune
      disorder of peripheral nerves that develops in susceptible individuals after
      infection and, in rare cases, after immunisation. Exposure to influenza via
      infection or vaccination has been associated with GBS. We review the relation
      between GBS and these routes of exposure. Epidemiological studies have shown
      that, except for the 1976 US national immunisation programme against swine-origin
      influenza A H1N1 subtype A/NJ/76, influenza vaccine has probably not caused GBS
      or, if it has, rates have been extremely low (less than one case per million
      vaccine recipients). By contrast, influenza-like illnesses seem to be relevant
      triggering events for GBS. The concerns about the risk of inducing GBS in mass
      immunisation programmes against H1N1 2009 do not, therefore, seem justified by
      the available epidemiological data. However, the experiences from the 1976 swine
      flu vaccination programme emphasise the importance for active and passive
      surveillance to monitor vaccine safety.

PMID- 20797645
TI  - Do children infected with HIV receiving HAART need to be revaccinated?
AB  - No official recommendations have been made on whether children infected with HIV
      on highly active antiretroviral therapy (HAART) should be revaccinated. We
      reviewed published work to establish whether these children have protective
      immunity to vaccine-preventable diseases and to assess short-term and long-term
      immune responses to vaccination of children given HAART. In general, children on
      HAART had low levels of immunity to vaccines given before treatment. Most
      children on HAART, however, responded to revaccination, although immune
      reconstitution was not sufficient to ensure long-term immunity for some children.
      These results suggest that children on HAART would benefit from revaccination,
      but levels of protective immunity might need to be monitored and some children
      might need additional vaccine doses to maintain protective immunity. Vaccination
      policies and strategies for children infected with HIV on HAART should be
      developed in regions of high HIV prevalence to ensure adequate individual and
      population immunity.

PMID- 20797647
TI  - Cutaneous septic emboli from Candida tropicalis.

PMID- 20797648
TI  - Histopathologic inflammatory response induced by recombinant bone morphogenetic
      protein-2 causing radiculopathy after transforaminal lumbar interbody fusion.
AB  - BACKGROUND CONTEXT: A significant increase in off-label use of recombinant human
      bone morphogenic protein-2 (rhBMP-2) in posterior lumbar interbody fusion
      techniques has been seen in the spine community. Numerous reports have
      demonstrated complications with use of this proinflammatory agent; however, the
      in vivo response caused by rhBMP-2 has not been characterized on a cellular
      level. PURPOSE: To report the case of lumbar radiculopathy and the associated
      histopathologic findings stemming from the inflammatory response to rhBMP-2 used
      in transforaminal lumbar interbody fusion (TLIF) surgery. STUDY DESIGN/SETTING:
      Case report. PATIENT SAMPLE: Single patient case report of rhBMP-2 off-label use
      causing an inflammatory response that resulted in radiculopathy after TLIF
      surgery. OUTCOMES MEASURES: Clinical, radiologic, and histopathologic evidence
      was used to determine outcomes in this report. METHODS: A 27-year-old male
      presented with low back pain and radiculopathy and radiographic evidence of
      degenerative disc disease and foraminal stenosis. Four weeks after L4-L5 TLIF
      surgery augmented with rhBMP-2, the patient developed right-sided lower extremity
      radiculopathy. Magnetic resonance imaging of the lumbar spine demonstrated
      bilateral fluid collections with the larger right-sided mass compressing the
      right L4 nerve root. RESULTS: Surgical decompression of this mass resulted in
      resolution of his right-sided radicular symptoms. Histologic analysis of the
      surgical pathology demonstrated diffuse osteoid and woven bone amidst a
      fibrovascular stroma densely populated by lymphocytes and eosinophils.
      CONCLUSIONS: Off-label rhBMP-2 use in posterior interbody fusion techniques can
      lead to complications. This case serves to identify potential hazards of this
      growth factor and highlight areas for further study to better understand its in
      vivo behavior.

PMID- 20797649
TI  - Vertebral body fracture after anterolateral instrumentation and interbody fusion
      in two osteoporotic patients.
AB  - BACKGROUND CONTEXT: The XLP plate is an anterolateral instrumentation system
      developed as a part of the eXtreme Lateral Interbody Fusion (XLIF) system for
      lateral transpsoas interbody fusion, an alternative to anterior interbody fusion.
      PURPOSE: To report two cases of atraumatic coronal plane vertebral body fractures
      in the early postoperative period after interbody fusion using XLIF cages,
      lateral plating using the XLP plate, and unilateral posterior pedicle screw
      instrumentation. STUDY DESIGN: Case report. METHODS/SUMMARIES: Both patients were
      septuagenarian women with normal body mass indices and osteoporosis. The patients
      underwent L4-L5 XLIF with anterolateral instrumentation followed by posterior
      decompression and fusion using unilateral pedicle screws. In the early
      postoperative period (<or=6 weeks), the patients developed acute onset of severe
      low back pain without history of trauma. Imaging demonstrated coronal plane
      vertebral body fracture through the screw hole of the XLP plate in the superior
      vertebral body in one case and the inferior vertebral body in the other. One
      patient required kyphoplasty at the L4 level for pain relief. The other was
      treated conservatively. The nondisplaced fractures went on to union with pain
      resolution and successful fusion in both patients. RESULTS: Coronal plane
      fractures occurred in 2 of 13 patients treated by the senior author using XLIF,
      the XLP plate, and unilateral pedicle screw instrumentation. Osteoporosis was
      likely a contributing factor in both patients. One potential mechanism for this
      unusual fracture pattern is subsidence of the cage with resultant cut-through of
      the fixed-angle screws through the osteoporotic vertebral body. Alternately, the
      fracture could have resulted from the stress riser created by the screw hole
      traversing an area of relative stress concentration directly adjacent to the
      cage. CONCLUSION: Coronal plane vertebral fracture may occur in osteoporotic
      patients treated with XLIF and XLP lateral instrumentation. Unilateral pedicle
      screw instrumentation does not prevent this complication.

PMID- 20797650
TI  - Bilateral acute angle-closure glaucoma as a complication of facedown spine
      surgery.
AB  - BACKGROUND CONTEXT: Multiple studies have reported that facedown positioning can
      result in elevation of intraocular pressure (IOP) in individuals susceptible to
      angle-closure glaucoma. Before advances in diagnostic modalities, prone tests
      were popularly performed in ophthalmology practices as provocative tests for
      detecting potentially occludable angles. In patients with a positive test result,
      direct observation shows that the anterior chamber shallows and the angle closes
      over time, compromising aqueous humor outflow facility. Furthermore, the degree
      of angle narrowing is proportional to the rise in IOP. A common scenario
      involving a prone position is spine surgery, which can last several hours with
      the patient unconscious. PURPOSE: To report a case of a patient who developed
      bilateral acute angle-closure glaucoma after facedown spine surgery. STUDY
      DESIGN: Case report and literature review. METHODS: A 68-year-old Caucasian woman
      presented with persistent low back and left lower extremity pain. History was
      remarkable for L5 radicular pain, spinal stenosis, and an L3-L4 laminectomy
      performed 6 months previously. Plain films showed instability at the L4-L5 level
      and degenerative disc disease and scoliosis at L2-L4. The patient underwent
      spinal fusion surgery. RESULTS: Postoperatively, the patient complained of pain
      in the left eye accompanied with nausea and vomiting. Ophthalmology consultation
      confirmed the diagnosis of bilateral acute angle-closure glaucoma, requiring
      medical therapy initially followed by laser iridotomies in both eyes.
      CONCLUSIONS: Bilateral acute angle-closure glaucoma may occur as a complication
      of facedown spine surgery. It is essential for anesthesiologists and surgeons to
      be aware of this complication for accurate diagnosis and timely intervention. A
      preoperative evaluation by an ophthalmologist should be considered for those
      individuals who are at increased risk of developing angle-closure glaucoma, such
      as certain ethnicities, including Asians, Canadians, and Eskimos; female gender;
      hyperopic eyes with a shorter axial length; family history; history of previous
      attacks in the subject; and so forth. Prophylactic laser iridotomy in eyes with
      potentially occludable angles is a simple and safe office procedure that can
      prevent potentially devastating visual outcomes.

PMID- 20797651
TI  - Reporting and statistically comparing averages of a patient cohort: the glass may
      really be half empty.
AB  - COMMENTARY ON: Nandakumar A, Clark NA, Peehal JP, et al. The increase in dural
      sac area is maintained at 2 years after X-stop implantation for the treatment of
      spinal stenosis with no significant alteration in lumbar spine range of movement.
      Spine J 2010:10:762-768 (in this issue).

PMID- 20797652
TI  - Quantifying scoliosis: we are still not there.
AB  - COMMENTARY ON: Tanure MC, Pinheiro AP, Oliveira AS. Reliability assessment of
      Cobb angle measurements using manual and digital methods. Spine J 2010:10:769-774
      (in this issue).

PMID- 20797653
TI  - The compromise between motion preservation and arthrodesis.
AB  - COMMENTARY ON: Cunningham BW, Dawson JM, Hu N, et al. Preclinical evaluation of
      the Dynesys posterior spinal stabilization system: a nonhuman primate model.
      Spine J 2010;10:775-83 (in this issue).

PMID- 20797654
TI  - Synovial cysts: to fuse or not to fuse?
AB  - COMMENTARY ON: Bydon A, Xu R, Parker SL, et al. Recurrent back and leg pain and
      cyst reformation after surgical resection of spinal synovial cysts: systemic
      review of reported postoperative outcomes. Spine J 2010;10:820-826 (in this
      issue).

PMID- 20797655
TI  - Use of evidence-based decision-making in private practice for emergency treatment
      of dental trauma: EB case report.
AB  - OBJECTIVE: This article illustrates the use of the evidence-based process in
      clinical practice to answer questions that arose when a patient presented with
      dental trauma. BACKGROUND: The patient had avulsion of the maxillary right
      central incisor and lateral luxation and alveolar bone fracture partially
      encasing the roots of the maxillary left central and lateral incisors. At the
      emergency treatment the dentist replanted the teeth but had 2 questions regarding
      the impending treatment for the patient regarding the optimal timing of root
      canal therapy and splint duration that would result in the best outcome and
      prognosis for healing. METHOD: The evidence-based process was used to help answer
      the clinical queries. Two focused clinical (PICO) questions were written, and 2
      separate searches were conducted for each PICO question. Four databases were
      searched for systematic reviews, meta-analyses, critical summaries and practice
      guidelines. RESULTS: A total of 3 systematic reviews, 8 practice guidelines, 1
      critical summary, and 1 Cochrane protocol were found. CONCLUSION: For replanted
      avulsed teeth, with closed apices, successful periodontal healing is improved
      when elective extirpation of the pulps occurs within 14 days. Second, guidelines
      recommend a flexible splint for up to 2 weeks for avulsed teeth with an extension
      of 2 to 4 weeks possibly needed for lateral luxation and with breakdown of
      marginal bone. However, evidence shows that an association between short-term
      splinting and an increased likelihood of functional periodontal healing,
      acceptable healing, or decreased development of replacement resorption, appears
      inconclusive and that the types of splint and the fixation period are not
      significant variables when related to healing outcomes. The evidence-based method
      was efficient, and very helpful in optimizing the management of the emergency
      dental treatment.

PMID- 20797656
TI  - Although randomized controlled trials support the evidence base for the several
      different measures to prevent or manage xerostomia following cancer treatment,
      intensity-modified radiotherapy (IMRT) should be used when possible.

PMID- 20797657
TI  - Still no convincing link between temporomandibular disorders and orthognathic
      surgery.

PMID- 20797658
TI  - Ankyloglossia may cause breastfeeding, tongue mobility, and speech difficulties,
      with inconclusive results on treatment choices.

PMID- 20797659
TI  - Casein phosphopeptide used in toothpaste suggests an efficacy similar to
      toothpaste containing sodium monofluorophosphate for caries prevention.

PMID- 20797660
TI  - Replacement rates may vary for amalgam versus nonmetal restorations.

PMID- 20797661
TI  - Younger adults with oral cavity squamous cell cancer have a significantly higher
      5-year survival rate than do older adults in the united states, controlling for
      patient- and disease-specific characteristics.

PMID- 20797662
TI  - Topical anesthetics are more effective in diminishing pain from needle stick
      insertion alone compared to reducing pain from insertion with anesthetic
      injection.

PMID- 20797663
TI  - Dental, medical and psychosocial factors may be critical factors for retaining
      functional dentition into very old age.

PMID- 20797664
TI  - A short intervention to encourage dental flossing may be more effective if the
      individual has already formed a behavioral intention to floss compared with an
      individual who has a more deliberative mindset.

PMID- 20797665
TI  - Limited benefit of surgical intervention of oral epithelial dysplasia in the
      prevention of recurrences and malignant development.

PMID- 20797666
TI  - Variants in the melanocortin-1 receptor (MC1R) gene appear to be associated with
      increased dental care-related anxiety, increased fear of dental pain, and greater
      likelihood of dental care avoidance.

PMID- 20797667
TI  - Serologically determined in utero exposure to oral pathogens may be associated
      with increased risk for neonatal intensive care unit (NICU) admissions and length
      of stay.

PMID- 20797668
TI  - The frequency of human papilloma virus (HPV) is higher in premalignant and
      malignant oral mucosal lesions than normal mucosa.

PMID- 20797669
TI  - Dental erosion in a series of referred patients was statistically associated with
      gastric reflux, acidic drink intake of more than 0.5 L per day, and low salivary
      buffering capacity.

PMID- 20797670
TI  - Lifelong exposure to fluoride at 1.1 ppm (1.1 mg/L) in drinking water promotes
      the remineralization of caries lesions.

PMID- 20797671
TI  - A description of emergency department visits for dental problems not related to
      trauma in Ontario, Canada.

PMID- 20797672
TI  - The prevalence of smokeless tobacco use remained low and unchanged among US men
      in 2000-2005 while smoking declined.

PMID- 20797675
TI  - Functions of claudin tight junction proteins and their complex interactions in
      various physiological systems.
AB  - Members of the claudin family of proteins are the main components of tight
      junctions (TJs), the major selective barrier of the paracellular pathway between
      epithelial cells. As such, the claudins have the ability to generate the TJ
      physiological barrier and to control various physiological processes. Therefore,
      the importance of this family of proteins is obvious and many efforts were made
      to reveal different aspects of claudin TJ protein biology. In this review, we
      discuss recent advances in our understanding of claudin structure and function,
      as well as their distribution pattern in different organs and tissues. We mainly
      highlight the complex interactions of claudins in various physiological systems
      and suggest a possible role for a coregulation mechanism.

PMID- 20797676
TI  - Secondary symbiosis between Paramecium and Chlorella cells.
AB  - Each symbiotic Chlorella species of Paramecium bursaria is enclosed in a
      perialgal vacuole (PV) membrane derived from the host digestive vacuole (DV)
      membrane. Algae-free paramecia and symbiotic algae are capable of growing
      independently and paramecia can be reinfected experimentally by mixing them. This
      phenomenon provides an excellent model for studying cell-to-cell interaction and
      the evolution of eukaryotic cells through secondary endosymbiosis between
      different protists. However, the detailed algal infection process remains
      unclear. Using pulse labeling of the algae-free paramecia with the isolated
      symbiotic algae and chase method, we found four necessary cytological events for
      establishing endosymbiosis. (1) At about 3 min after mixing, some algae show
      resistance to the host lysosomal enzymes in the DVs, even if the digested ones
      are present. (2) At about 30 min after mixing, the alga starts to escape from the
      DVs as the result of the budding of the DV membrane into the cytoplasm. (3)
      Within 15 min after the escape, the DV membrane enclosing a single green alga
      differentiates to the PV membrane, which provides protection from lysosomal
      fusion. (4) The alga localizes at the primary lysosome-less host cell surface by
      affinity of the PV to unknown structures of the host. At about 24 h after mixing,
      the alga multiplies by cell division and establishes endosymbiosis. Infection
      experiments with infection-capable and infection-incapable algae indicate that
      the infectivity of algae is based on their ability to localize beneath the host
      surface after escaping from the DVs. This algal infection process differs from
      known infection processes of other symbiotic or parasitic organisms to their
      hosts.

PMID- 20797677
TI  - Molecular basis of peroxisome division and proliferation in plants.
AB  - Peroxisomes are multifunctional organelles whose abundance varies depending on
      the cell type, organism, developmental stage, and environmental and metabolic
      conditions in which the organism lives. Plant peroxisomes are essential to embryo
      viability and are involved in numerous biochemical processes in development and
      in plant interaction with the environment. In the past few years, several classes
      of peroxisomal proteins required for various steps in peroxisome division and
      proliferation and a signaling pathway underlying the light induction of
      peroxisome proliferation have been identified from the model plant species
      Arabidopsis thaliana. Some of the major components of the peroxisome division
      apparatus have been conserved from plants to yeasts and animals, whereas plant
      specific components are also being revealed. Environmental factors and nuclear
      events that control the process appear to be highly unique in different
      evolutionary lineages. Future research needs to identify additional members of
      the peroxisome division/proliferation pathways and to dissect signaling pathways
      by which various environmental and metabolic cues regulate the abundance of
      peroxisomes in plants.

PMID- 20797678
TI  - New insights into the signal transmission from taste cells to gustatory nerve
      fibers.
AB  - Taste receptor cells detect chemical compounds in the oral cavity and transfer
      their messages to gustatory afferent nerve fibers. Considering the coding of
      taste information, the sensitivity of taste cells and the connection between
      taste cells and gustatory fibers may be critical in this process. Broadly tuned
      taste cells and random connections between taste cells and fibers would produce
      gustatory fibers that have broad sensitivity to multiple taste qualities.
      Narrowly tuned taste cells and selective connections would yield gustatory nerve
      fibers that respond to specific taste quality. This review summarizes results
      showing molecular and morphological aspects of taste bud cells, physiological
      responses of taste cells, possible connections between taste cells and gustatory
      fibers, and transmitter release from taste cells, and discusses how taste
      qualities are encoded among taste bud cells and how taste information is
      transmitted from taste cells to gustatory nerve fibers.

PMID- 20797679
TI  - New insights into the regulation of ion channels by integrins.
AB  - By controlling cell adhesion to the extracellular matrix, integrin receptors
      regulate processes as diverse as cell migration, proliferation, differentiation,
      apoptosis, and synaptic stability. Because the underlying mechanisms are
      generally accompanied by changes in transmembrane ion flow, a complex interplay
      occurs between integrins, ion channels, and other membrane transporters. This
      reciprocal interaction regulates bidirectional signal transduction across the
      cell surface and may take place at all levels of control, from transcription to
      direct conformational coupling. In particular, it is becoming increasingly clear
      that integrin receptors form macromolecular complexes with ion channels. Besides
      contributing to the membrane localization of the channel protein, the
      integrin/channel complex can regulate a variety of downstream signaling pathways,
      centered on regulatory proteins like tyrosine kinases and small GTPases. In turn,
      the channel protein usually controls integrin activation and expression. We
      review some recent advances in the field, with special emphasis on hematology and
      neuroscience. Some oncological implications are also discussed.

PMID- 20797680
TI  - Natriuretic peptides in the regulation of the hypothalamic-pituitary-adrenal
      axis.
AB  - Atrial (ANP), brain (BNP), and C-type (CNP) natriuretic peptides act by binding
      to three main subtypes of receptors, named NPR-A, -B, and -C. NPR-A and NPR-B are
      coupled with guanylate cyclase. Not only NPR-C is involved in removing
      natriuretic peptides from the circulation but it also acts through inhibition of
      adenylyl cyclase. NPR-A binds ANP and BNP; NPR-B preferentially binds CNP; and
      NPR-C binds all natriuretic peptides with similar affinities. All natriuretic
      peptides and their receptors are widely present in the hypothalamus, pituitary,
      adrenal cortex, and medulla. In the hypothalamus, they reduce norepinephrine
      release, inhibit oxytocin, vasopressin, corticotropin-releasing factor, and
      luteinizing hormone-releasing hormone release. In the hypophysis, natriuretic
      peptides inhibit basal and induced ACTH release. Conversely, the effects of
      natriuretic peptides on secretion of growth, luteinizing, and follicle
      stimulating hormones are not clear. Natriuretic peptides are known to inhibit
      basal and stimulated aldosterone secretion, through an increase of intracellular
      cGMP, and to inhibit the growth of zona glomerulosa. Inhibition or stimulation of
      glucocorticoid secretion by adrenocortical cells has been reported on the basis
      of the species involved, and an indirect effect mediated by adrenalmedullary
      cells has been hypothesized. In the adrenal medulla, natriuretic peptides inhibit
      catecholamine release and increase catecholamine uptake. It appears that
      natriuretic peptides may play a role in the pathophysiology of adrenocortical
      neoplasias and pheochromocytomas.

PMID- 20797681
TI  - Evidence for multiple photosystems in jellyfish.
AB  - Cnidarians are often used as model animals in studies of eye and photopigment
      evolution. Most cnidarians display photosensitivity at some point in their
      lifecycle ranging from extraocular photoreception to image formation in camera
      type eyes. The available information strongly suggests that some cnidarians even
      possess multiple photosystems. The evidence is strongest within Cubomedusae where
      all known species posses 24 eyes of four morphological types. Physiological
      experiments show that each cubomedusan eye type likely constitutes a separate
      photosystem controlling separate visually guided behaviors. Further, the visual
      system of cubomedusae also includes extraocular photoreception. The evidence is
      supported by immunocytochemical and molecular data indicating multiple
      photopigments in cubomedusae as well as in other cnidarians. Taken together,
      available data suggest that multiple photosystems had evolved already in early
      eumetazoans and that their original level of organization was discrete sets of
      special-purpose eyes and/or photosensory cells.

PMID- 20797682
TI  - Membrane trafficking in protozoa SNARE proteins, H+-ATPase, actin, and other key
      players in ciliates.
AB  - Due to their well-defined pathways of vesicle trafficking and manyfold mutants
      ciliates have served as good model systems. Further studies required the
      development of databases, now available for Paramecium and Tetrahymena. A variety
      of key players have been identified and characterized based on BLAST search,
      domain analysis, localization, and gene-silencing studies. They include NSF (N
      ethylmaleimide sensitive factor), SNAREs (soluble NSF attachment protein [SNAP]
      receptors), the H(+)-ATPase (V-ATPase) and actin, while Arf (ADP-ribosylation
      factor) and Rab-type small GTPases, COPs (coatamer proteins) and many others
      remain to be elucidated. The number of SNAREs, H(+)-ATPase subunits, and actins
      ever found within one cell type are unexpectedly high and most of the manifold
      vesicle types seem to be endowed with specific molecular components pertinent to
      trafficking. As in higher eukaryotes, multifactorial targeting likely occurs. It
      appears that, in parallel to higher organisms, ciliates have evolved a similar
      structural and molecular complexity of vesicle trafficking.

PMID- 20797683
TI  - New insights into the types and function of proteases in plastids.
AB  - Plastids change their morphology dynamically in response to environmental
      conditions and developmental status. Related to these plastid dynamics, the
      quality and quantity controls of proteins are necessary. Therefore, proteases are
      important as key regulators in almost all processes during the conversion of
      plastid types and the maintenance of plastid homeostasis. Recent progress in this
      field has revealed that various proteases and peptidases act on plastids. Results
      of the studies indicate that the vast majority of plastid proteases are
      homologous to prokaryotic ones because plastids are thought to originate from
      endosymbiosis of ancestral cyanobacteria. Moreover, the diversification of
      subunits of several plastid proteases has been revealed along with new insights
      into the functions of these homologues. This review provides basic information
      related to plastid proteases and the current view of their physiological roles in
      plastid homeostasis and biogenesis.

PMID- 20797684
TI  - Impact of ATP-binding cassette transporters on human immunodeficiency virus
      therapy.
AB  - Even though potent antiretrovirals are available against human immunodeficiency
      virus (HIV)-1 infection, therapy fails in a significant fraction of patients.
      Among the most relevant reasons for treatment failure are drug toxicity and side
      effects, but also the development of viral resistance towards the drugs applied.
      Efflux by ATP-binding cassette (ABC-) transporters represents one major mechanism
      influencing the pharmacokinetics of antiretroviral drugs and particularly their
      distribution, thus modifiying the concentration within the infected cells, that
      is, at the site of action. Moreover, drug-drug interactions may occur at the
      level of these transporters and modulate their activity or expression thus
      influencing the efficacy and toxicity of the substrate drugs. This review
      summarizes current knowledge on the interaction of antiretrovirals used for HIV-1
      therapy with ABC-transporters and highlights the impact of ABC-transporters for
      cellular resistance and therapeutic success. Moreover, the suitability of
      different cell models for studying the interaction of antiretrovirals with ABC
      transporters is discussed.

PMID- 20797685
TI  - New insights into the circadian clock in Chlamydomonas.
AB  - The unicellular green alga Chlamydomonas reinhardtii has long been used in
      research on circadian rhythm. Various circadian rhythms in behavior and
      physiology including phototaxis, chemotaxis, the cell division cycle, UV
      sensitivity, stickiness to glass (changes in properties of the cell surface), and
      starch content are observed in this alga. Soon after the isolation of clock
      mutants in Drosophila melanogaster and Neurospora crassa, clock mutants were also
      isolated in Chlamydomonas. Whereas genes responsible (clock genes) in Drosophila
      and Neurospora mutants have been identified and these organisms have become
      important models for understanding the circadian clock, Chlamydomonas clock genes
      have not been identified and the molecular basis of the algal clock was unclear
      until a few years ago. Recently, reverse and forward genetic studies revealed
      several clock genes in Chlamydomonas. These studies unveiled that the
      Chlamydomonas clock consists of both original and plant-like components. Further
      study of the Chlamydomonas circadian clock should provide new insights into the
      evolution of plant clocks. Furthermore, the identification of its clock genes
      makes Chlamydomonas a new model for molecular studies of the circadian
      oscillatory mechanisms in eukaryotes. Its simple cellular architecture may
      provide significant advantages for a comprehensive understanding of the
      intracellular temporal organization, especially between the nucleus and
      chloroplast.

PMID- 20797686
TI  - Comparing 5/7 and 2/9: Adults can do it by accessing the magnitude of the whole
      fractions.
AB  - This study investigated adults' ability to compare the magnitude of fractions
      without common components (e.g., 5/7 and 3/8), and the representation accessed in
      that process. We hypothesized that the absence of common components would enhance
      access to the magnitude of the fractions (i.e., a holistic representation) rather
      than a direct comparison of the numerators or the denominators. This hypothesis
      was tested in four between-subject conditions. Two types of experimental pairs
      were used that differed in the congruity of the magnitude of the denominator and
      the magnitude of the fraction. Each type of experimental pair was presented
      either alone or with filler pairs that introduced variability into the congruity
      of the components. In all four conditions, accuracy was above chance and the
      effect of the distance between the fractions on response times was significant,
      indicating an access to the magnitude of the fractions. Nevertheless, the
      variability of the congruity of the components had also a significant effect on
      performance, suggesting that the relative magnitude of the components was also
      processed. In conclusion, the representation of the fraction magnitude is hybrid,
      rather than purely holistic, in a magnitude-comparison task on fractions without
      common components.

PMID- 20797687
TI  - Mutations in ABHD12 cause the neurodegenerative disease PHARC: An inborn error of
      endocannabinoid metabolism.
AB  - Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC)
      is a neurodegenerative disease marked by early-onset cataract and hearing loss,
      retinitis pigmentosa, and involvement of both the central and peripheral nervous
      systems, including demyelinating sensorimotor polyneuropathy and cerebellar
      ataxia. Previously, we mapped this Refsum-like disorder to a 16 Mb region on
      chromosome 20. Here we report that mutations in the ABHD12 gene cause PHARC
      disease and we describe the clinical manifestations in a total of 19 patients
      from four different countries. The ABHD12 enzyme was recently shown to hydrolyze
      2-arachidonoyl glycerol (2-AG), the main endocannabinoid lipid transmitter that
      acts on cannabinoid receptors CB1 and CB2. Our data therefore represent an
      example of an inherited disorder related to endocannabinoid metabolism. The
      endocannabinoid system is involved in a wide range of physiological processes
      including neurotransmission, mood, appetite, pain appreciation, addiction
      behavior, and inflammation, and several potential drugs targeting these pathways
      are in development for clinical applications. Our findings show that ABHD12
      performs essential functions in both the central and peripheral nervous systems
      and the eye. Any future drug-mediated interference with this enzyme should
      consider the potential risk of long-term adverse effects.

PMID- 20797688
TI  - A mutation in ZNF513, a putative regulator of photoreceptor development, causes
      autosomal-recessive retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) is a phenotypically and genetically heterogeneous group
      of inherited retinal degenerations characterized clinically by night blindness,
      progressive constriction of the visual fields, and loss of vision, and
      pathologically by progressive loss of rod and then cone photoreceptors. Autosomal
      recessive RP (arRP) in a consanguineous Pakistani family previously linked to
      chromosome 2p22.3-p24.1 is shown to result from a homozygous missense mutation
      (c.1015T>C [p.C339R]) in ZNF513, encoding a presumptive transcription factor.
      znf513 is expressed in the retina, especially in the outer nuclear layer, inner
      nuclear layer, and photoreceptors. Knockdown of znf513 in zebrafish reduces eye
      size, retinal thickness, and expression of rod and cone opsins and causes
      specific loss of photoreceptors. These effects are rescued by coinjection with
      wild-type (WT) but not p.C339R-znf513 mRNA. Both normal and p.C339R mutant ZNF513
      proteins expressed in COS-7 cells localize to the nucleus. ChIP analysis shows
      that only the wild-type but not the mutant ZNF513 binds to the Pax6, Sp4, Arr3,
      Irbp, and photoreceptor opsin promoters. These results suggest that the ZNF513
      p.C339R mutation is responsible for RP in this family and that ZNF513 plays a key
      role in the regulation of photoreceptor-specific genes in retinal development and
      photoreceptor maintenance.

PMID- 20797689
TI  - Direct measure of the de novo mutation rate in autism and schizophrenia cohorts.
AB  - The role of de novo mutations (DNMs) in common diseases remains largely unknown.
      Nonetheless, the rate of de novo deleterious mutations and the strength of
      selection against de novo mutations are critical to understanding the genetic
      architecture of a disease. Discovery of high-impact DNMs requires substantial
      high-resolution interrogation of partial or complete genomes of families via
      resequencing. We hypothesized that deleterious DNMs may play a role in cases of
      autism spectrum disorders (ASD) and schizophrenia (SCZ), two etiologically
      heterogeneous disorders with significantly reduced reproductive fitness. We
      present a direct measure of the de novo mutation rate (MU) and selective
      constraints from DNMs estimated from a deep resequencing data set generated from
      a large cohort of ASD and SCZ cases (n = 285) and population control individuals
      (n = 285) with available parental DNA. A survey of ~430 Mb of DNA from 401
      synapse-expressed genes across all cases and 25 Mb of DNA in controls found 28
      candidate DNMs, 13 of which were cell line artifacts. Our calculated direct
      neutral mutation rate (1.36 * 10(-8)) is similar to previous indirect estimates,
      but we observed a significant excess of potentially deleterious DNMs in ASD and
      SCZ individuals. Our results emphasize the importance of DNMs as genetic
      mechanisms in ASD and SCZ and the limitations of using DNA from archived cell
      lines to identify functional variants.

PMID- 20797690
TI  - Mutations in DHDPSL are responsible for primary hyperoxaluria type III.
AB  - Primary hyperoxaluria (PH) is an autosomal-recessive disorder of endogenous
      oxalate synthesis characterized by accumulation of calcium oxalate primarily in
      the kidney. Deficiencies of alanine-glyoxylate aminotransferase (AGT) or
      glyoxylate reductase (GRHPR) are the two known causes of the disease (PH I and
      II, respectively). To determine the etiology of an as yet uncharacterized type of
      PH, we selected a cohort of 15 non-PH I/PH II patients from eight unrelated
      families with calcium oxalate nephrolithiasis for high-density SNP microarray
      analysis. We determined that mutations in an uncharacterized gene, DHDPSL, on
      chromosome 10 cause a third type of PH (PH III). To overcome the difficulties in
      data analysis attributed to a state of compound heterozygosity, we developed a
      strategy of "heterozygosity mapping"-a search for long heterozygous patterns
      unique to all patients in a given family and overlapping between families,
      followed by reconstruction of haplotypes. This approach enabled us to determine
      an allelic fragment shared by all patients of Ashkenazi Jewish descent and
      bearing a 3 bp deletion in DHDPSL. Overall, six mutations were detected: four
      missense mutations, one in-frame deletion, and one splice-site mutation. Our
      assumption is that DHDPSL is the gene encoding 4-hydroxy-2-oxoglutarate aldolase,
      catalyzing the final step in the metabolic pathway of hydroxyproline.

PMID- 20797691
TI  - A focal epilepsy and intellectual disability syndrome is due to a mutation in
      TBC1D24.
AB  - We characterized an autosomal-recessive syndrome of focal epilepsy, dysarthria,
      and mild to moderate intellectual disability in a consanguineous Arab-Israeli
      family associated with subtle cortical thickening. We used multipoint linkage
      analysis to map the causative mutation to a 3.2 Mb interval within 16p13.3 with a
      LOD score of 3.86. The linked interval contained 160 genes, many of which were
      considered to be plausible candidates to harbor the disease-causing mutation. To
      interrogate the interval in an efficient and unbiased manner, we used targeted
      sequence enrichment and massively parallel sequencing. By prioritizing unique
      variants that affected protein translation, a pathogenic mutation was identified
      in TBC1D24 (p.F251L), a gene of unknown function. It is a member of a large gene
      family encoding TBC domain proteins with predicted function as Rab GTPase
      activators. We show that TBC1D24 is expressed early in mouse brain and that
      TBC1D24 protein is a potent modulator of primary axonal arborization and
      specification in neuronal cells, consistent with the phenotypic abnormality
      described.

PMID- 20797692
TI  - [Heart transplantation for patients on high emergency list with or without
      extracorporeal membrane oxygenation support].
AB  - OBJECTIVE: Severely impaired patients may wait in France on a special and
      temporary high emergency national list (called SU). Some of these patients need
      mechanical circulatory support with ECMO. In order to compare two groups of
      patients on SU, who acceeded to heart transplantation (HT) with or without ECMO,
      we reviewed retrospectively 20 consecutive patients transplanted on SU between
      January 2004 and September 2007 in Rennes. PATIENTS AND METHODS: Among them, 10
      were transplanted without ECMO and 10 others were implanted with a femoro-femoral
      ECMO before HT. RESULTS: (1) Considering the group SU without pretransplantation
      ECMO: 2 years survival rate was 70%. Mean hospital stay was 26.4 days. Three
      patients were implanted with ECMO for graft dysfunction during postoperative
      course, without inherent complication. None graft dysfunction occurred after
      initial hospitalization; (2) considering the group SU with pretransplantation
      ECMO: 2 years survival rate was 90% (one early death). Mean hospital stay was 45
      days with multiple complications due to the ECMO (leg's ischemia: n = 2; lung
      oedema: n = 1; lymphorrhea: n = 3, low flow requiring change of canulae: n = 1).
      None graft dysfunction occurred after initial hospitalization. CONCLUSION:
      Although we didn't reach statistical significance, it seems that ECMO for
      patients in SU may be useful as bridge to transplant but with a higher morbidity
      than for similar patients transplanted without ECMO. Additional data from other
      transplant centers are needed to confirm our findings.

PMID- 20797693
TI  - Car egress analysis of younger and older drivers for motion simulation.
AB  - This paper presents a detailed description of car egress motion by younger and
      older participants. The objective of these analyses is to gather knowledge about
      egress motion in order to simulate them using a Digital Human Model. Seven young
      (from 20 to 35 years old) and eighteen older volunteers (from 63 to 82 years old)
      participated in the experiment. Their ingress and egress motions were captured
      for 4 different types of car. Motions were reconstructed through inverse
      kinematics using the RPx Software and the RAMSIS model. Motions were analysed
      through the interactions between the participant and the environment. Key-frames
      were defined in order to split the motionsup. Two main car egress strategies were
      observed: 'Left Leg first' (LLF) and 'Two Legs Out' (TLO). Only older
      participants used the TLO strategy. For each strategy, a detailed motion
      description is presented together with the identification of sub-strategies and
      constraints. The motion descriptions and the constraints also help to better
      understand the difficulties of older people when getting out of a car. All motion
      constraints described in this study should be considered to simulate realistic
      egress motion.

PMID- 20797694
TI  - Nonlinear regression equations for segmental mass-inertial characteristics of
      Korean adults estimated using three-dimensional range scan data.
AB  - Human modeling and the biomechanical analysis of human movement require the
      accurate estimation of body segment parameters for various populations and
      individuals. In this study, the body characteristics of adult Koreans were
      investigated using three-dimensional range scan data for 40 males and 40 females
      aged between 18 and 59 years obtained from the SizeKorea anthropometric database.
      Each subject was divided into 16 segments, and the mass-inertial parameters of
      each segment were calculated under the assumption of a uniform density
      distribution for the segment. The length and at least one circumference of each
      segment were determined from the scan data for that segment. Nonlinear regression
      equations were then derived based on the segment lengths and circumferences. The
      body segment parameters of Korean adults can be estimated using these equations
      if the required dimensions are measured directly or derived from an
      anthropometric database.

PMID- 20797695
TI  - Identification of SNP markers on 1p36 and association analysis of EPB41 with
      mandibular prognathism in a Chinese population.
AB  - OBJECTIVE: The results of a genome-wide scan suggested that chromosome locus 1p36
      might be linked to the etiology of mandibular prognathism (MP) amongst Asian
      ethnicities. In this study, we performed a two-stage case-control association
      study to determine whether one or more genes that confer susceptibility to MP are
      located within this genomic region. DESIGN: In the first stage of the study, we
      examined 103 single nucleotide polymorphisms (SNPs) on 1p36 across an 8.6Mb
      critical region and within four candidate genes in 158 cases and 147 controls to
      identify genes associated with MP. In the second stage of the study, we examined
      an additional 23 SNPs within the erythrocyte membrane protein band 4.1 (EPB41)
      gene in 211 cases and 224 controls. RESULTS: Four SNPs located in the EPB41 gene
      showed possible allelic and genotypic associations with MP (P<0.03 and P<0.05,
      respectively) in the first stage. In the analysis of single SNPs in the second
      stage, the allele of rs4654388 showed the strongest significant association with
      MP (P=0.008) and the rs4654388 G-allele was associated with a significantly
      increased risk of MP (OR: 1.78, 95% CI: 1.16-2.74). Haplotype analysis revealed
      that MP was associated significantly with haplotype GTTCAGGT
      (P(corrected)=0.031), which included the rs4654388 G-allele. CONCLUSIONS: An
      association between genetic polymorphisms in the EPB41 gene and MP has been
      observed. Although the polymorphisms which may contribute to MP have not been
      determined, the results of our study suggest that the EPB41 gene could confer
      susceptibility to MP.

PMID- 20797696
TI  - Marijuana craving during a public speaking challenge: Understanding marijuana use
      vulnerability among women and those with social anxiety disorder.
AB  - Social anxiety disorder (SAD) is associated with risk for developing marijuana
      dependence, yet it remains unclear whether urge to use marijuana increases in
      anticipation of social anxiety-provoking situation, during the situation, or
      afterwards (to avoid post-event processing). The present study examined the
      timing of marijuana craving in response to a social anxiety task among 60 (50%
      female; 33% with SAD) marijuana users randomly assigned to either a speech or
      reading task. Participants completed ratings of marijuana craving at baseline
      (prior to being informed of task assignment), before, during, and after task.
      Among women and participants with SAD, the speech task was associated with
      greater craving than the reading task. This effect was particularly pronounced
      during the social anxiety induction task. This effect was not observed for men or
      participants without SAD. Identification of timing of urge to use marijuana has
      important implications for treatment and relapse prevention of marijuana problems
      among women and people with SAD (a group at particular risk for marijuana-related
      problems).

PMID- 20797697
TI  - The time course of attentional disengagement from angry faces in social anxiety.
AB  - While impaired attentional disengagement from threatening stimuli is thought to
      enhance social anxiety, it is unclear when the impaired disengagement occurs
      accurately. We used a gap task (Experiment 1) and an overlap task (Experiment 2)
      to reveal the impaired attentional disengagement from angry faces in socially
      anxious people with non-treatment seeking undergraduates. High (N = 17 in
      Experiments 1 and 2) and low socially anxious people (N = 17 in Experiment 1 and
      19 in Experiment 2) were asked to fixate on an angry or neutral face presented at
      the center of a screen. Then, they discriminated the peripheral target stimuli.
      When there was a temporal gap between the face and target in Experiment 1 (gap
      task), the reaction times (RTs) for angry and neutral faces did not differ for
      all participants. However, when there was no gap and the face continued to appear
      in Experiment 2 (overlap task), the RTs for angry faces in high socially anxious
      people were longer than those for neutral faces after presentation times of 300
      ms or longer. In low socially anxious people, the RTs following the angry and
      neutral faces did not differ. These results suggest that high socially anxious
      people face difficulty in disengaging attention from angry faces after
      recognizing them.

PMID- 20797698
TI  - Looking out for danger: An attentional bias towards spatially predictable
      threatening stimuli.
AB  - Attentional bias to threat is well established, however, the influence of spatial
      predictability on this attentional bias has never been investigated. Here we
      investigated how threat affects attentional capture and disengagement when its
      spatial location is predictable. Using a visual search paradigm, participants
      were required to identify a target inside one of a variable number of colored
      circles. One color (Conditioned Stimulus, CS+) was fear-conditioned using an
      electrocutaneous stimulus at tolerance level. In the experimental group the CS+
      was made spatially predictable (occurred more often at one location in the visual
      display), while this was not the case in the control group. Results showed no
      complete automatic capture of attention by the CS+, but the experimental group
      did show more prioritization of the CS+ and less difficulty to disengage from the
      CS+ than the control group. Of further importance was the finding that the
      experimental group also attended to the location that was predictive of the CS+,
      even when no CS+ was presented. Findings are discussed in terms the effects of
      predictability on anxiety.

PMID- 20797699
TI  - Structural analysis of arabinoxylans isolated from ball-milled switchgrass
      biomass.
AB  - Ball-milled alcohol-insoluble residue (AIR) was prepared from switchgrass
      (Panicum virgatum var Alamo) and sequentially extracted with 50 mM ammonium
      oxalate buffer, 50 mM sodium carbonate, 1 M KOH containing 1% NaBH(4), and 4 M
      KOH containing 1% NaBH(4). Arabinoxylan was the most abundant component of the 1
      M KOH-extracted fraction, which was treated with endoxylanase to generate
      oligosaccharides. Gel-permeation chromatography of these oligosaccharides
      produced three size-homogeneous oligosaccharide fractions with molecular weights
      of 678, 810, and 1074 Da, corresponding to 5, 6, and 8 pentose units,
      respectively. Detailed structural analysis of these oligosaccharides was
      performed using methylation analysis, multiple-step mass spectrometry (ESIMS(n)),
      and 1D and 2D NMR spectroscopy. The preferred gas-phase fragmentation pathways
      were identified for these oligosaccharides, providing extensive sequence
      information that was completely consistent with structures determined by ab
      initio NMR analysis. These results demonstrate the high information content of
      ESIMS(n) analysis when applied to cell-wall-derived oligosaccharides and provide
      standard data that will facilitate the analysis of cell-wall polysaccharide
      fragments with a sensitivity that is sufficient for the analysis of samples
      obtained from dissected tissues as well as other small samples.

PMID- 20797700
TI  - Filament-associated TSGA10 protein is expressed in professional antigen
      presenting cells and interacts with vimentin.
AB  - Testis-specific gene antigen 10 (TSGA10) encodes an 82-kDa protein expressed
      during development, and in testis and brain tissues. We report its expression in
      human monocyte-derived dendritic cells (DC) and macrophages in vitro and in
      murine spleen CD11c(+) cells ex vivo. An interaction between DC/macrophage
      derived TSGA10 and vimentin, as well as a few other major cytoskeletal proteins
      (e.g., actin-gamma1), was identified by pull-down and mass spectroscopy assays.
      The interaction between TSGA10 and vimentin was further confirmed by
      immunoprecipitation and immunolocalisation in transfected RAW267 and HEK293 cell
      lines. TSGA10 formed filamentous structures in transfected COS-1 cells and was
      observed in cellular projections. We propose that TSGA10 could influence the
      function of antigen presenting cells (APC) via its interaction with cytoskeletal
      proteins such as vimentin.

PMID- 20797701
TI  - Auto-antibodies to nuclear and nucleolar antigen and long-term exposure to
      inorganic mercury.

PMID- 20797702
TI  - Falloposcopic tuboplasty as an option for tubal infertility: an alternative to in
      vitro fertilization.
AB  - This is a case series to evaluate the efficacy of falloposcopic tuboplasty (FT),
      a surgical technique of recanalization of occluded fallopian tube. Of 153
      patients with tubal infertility for more than 2 years who underwent FT, 28.9% (44
      patients) conceived, and 27.3%, 75.0%, and 88.8% conceived in 1 month, 6 months,
      and 12 months after FT, respectively.

PMID- 20797703
TI  - A sperm viability test using SYBR-14/propidium iodide flow cytometry as a tool
      for rapid screening of primary ciliary dyskinesia patients and for choosing sperm
      sources for intracytoplasmic sperm injection.
AB  - Spermatozoa viability tests based on dual-color flow cytometry after staining
      with Sybr-14/propidium iodide were performed on 44 men with complete
      asthenospermia for primary ciliary dyskinesia (PCD) screening, and seven were
      identified with PCD by electron microscopy of ultrastructural ciliary defects.
      Six PCD patients underwent eight intracytoplasmic sperm injection therapy cycles
      using ejaculated sperm or testicular sperm, obtaining a mean fertilization rate
      of 46.6%, with three healthy babies born and one in utero at the time of writing.

PMID- 20797704
TI  - Functional association of interleukin-18 gene -607 C/A promoter polymorphisms
      with endometriosis.
AB  - This study evaluated for the first time the relationship between interleukin-18
      (IL-18) C607A genotypes and endometriosis in 135 women with endometriosis and 84
      controls. In the study population, IL-18 -607*A homozygote and A allele were
      positively correlated with the risk of developing endometriosis or the stage of
      endometriosis.

PMID- 20797706
TI  - Improving fertility preservation in cancer: ovarian tissue cryobanking followed
      by ovarian stimulation can be efficiently combined.
AB  - This pilot study evaluated whether combination of partial removal of ovarian
      tissue for cryobanking followed by ovarian stimulation and cryopreservation of
      oocytes can improve the efficacy of fertility preservation without further
      delaying cancer treatment. Initial partial removal of ovarian tissue did not
      substantially affect the average number and quality of retrieved oocytes after
      ovarian stimulation in this study.

PMID- 20797707
TI  - Failed IVF cycles and the risk of subsequent preeclampsia or fetal growth
      restriction: a case-control exploratory study.
AB  - OBJECTIVE: To investigate the hypothesis that women achieving pregnancy after two
      or more failed embryo transfers (ETs) of good quality embryos have increased
      incidence of preeclamptic toxemia (PET) or fetal growth restriction (FGR)
      compared with those conceiving in the first ET after in vitro fertilization
      (IVF). DESIGN: Case-control study. SETTING: Tertiary infertility center.
      PATIENT(S): Women who underwent IVF at the St. Mary's Hospital, Manchester,
      between January 2000 and June 2008 and conceived in the first ET, versus those
      who conceived after two or more failed ETs. INTERVENTION(S): Retrospective case
      note review. MAIN OUTCOME MEASURE(S): Incidence of PET or FGR. RESULT(S): Case
      notes of 364 eligible patients were identified: 125 conceived after two or more
      failed ETs and 239 in the first ET. The incidence of the primary outcome (PET or
      FGR) for the total number of pregnancies showed no significant difference between
      cases and controls (age and multiplicity adjusted odds ratio 1.2, 95% confidence
      interval 0.5-3.0). There were no significant differences between case and control
      subjects for the secondary outcomes. CONCLUSION(S): This study failed to
      demonstrate that women conceiving after two or more unsuccessful ETs are at
      increased risk of PET or FGR. More studies are required to investigate the
      relationship further.

PMID- 20797708
TI  - Luteal phase estradiol versus luteal phase estradiol and antagonist protocol for
      controlled ovarian stimulation before in vitro fertilization in poor responders.
AB  - Luteal phase synchronization of follicular growth has been suggested as a means
      to improve ovarian response in low responders. We compared luteal E2 and
      antagonist (n=256) with luteal E2 only (n=57) before antagonist protocol in low
      responders. The addition of GnRH antagonist to luteal E2 for luteal suppression
      before ovarian stimulation for IVF does not improve IVF outcomes in poor
      responders.

PMID- 20797709
TI  - Comprehensive embryo analysis of advanced maternal age-related aneuploidies and
      mosaicism by short comparative genomic hybridization.
AB  - The short comparative genomic hybridization (short-CGH) method was used to
      perform a comprehensive cytogenetic study of isolated blastomeres from advanced
      maternal age embryos, discarded after fluorescent in situ hybridization (FISH)
      preimplantation genetic screening (PGS), detecting aneuploidies (38.5% of which
      corresponded to chromosomes not screened by 9-chromosome FISH), structural
      aberrations (31.8%), and mosaicism (77.3%). The short-CGH method was subsequently
      applied in one PGS, achieving a twin pregnancy.

PMID- 20797711
TI  - Activation of adenosine A2A receptors by polydeoxyribonucleotide increases
      vascular endothelial growth factor and protects against testicular damage induced
      by experimental varicocele in rats.
AB  - In rat experimental varicocele, polydeoxyribonucleotide (PDRN) induces vascular
      endothelial growth factor (VEGF) production, thereby enhancing testicular
      function. This may point to a new therapeutic approach in human varicocele.

PMID- 20797712
TI  - Recurrent aberrations identified by array-CGH in patients with Mayer-Rokitansky
      Kuster-Hauser syndrome.
AB  - OBJECTIVE: To identify genetic causes of Mayer-Rokitansky-Kuster-Hauser (MRKH)
      syndrome. DESIGN: Prospective laboratory study. SETTING: University hospital.
      PATIENT(S): Fifty-six patients with MRKH syndrome. INTERVENTION(S):
      Identification of microdeletions and -duplications in a group of 48 MRKH patients
      by array-CGH. Results obtained by array-CGH were confirmed by RT-qPCR. Sequential
      analysis of two candidate genes LHX1 and HNF1B in a group of 56 MRKH patients.
      MAIN OUTCOME MEASURE(S): Identification of chromosomal regions and genes
      (recurrent and private) associated with MRKH syndrome. RESULT(S): We could
      delineate three definitively relevant regions (1q21.1, 17q12, and 22q11.21) and
      suggest that LHX1 und HNF1B are candidate genes for MRKH syndrome, because we
      identified recurrent deletions affecting these genes and a possible causative
      missense mutation in LHX1. CONCLUSION(S): Our findings suggest that different
      chromosomal regions are associated with MRKH syndrome.

PMID- 20797713
TI  - Endometriosis and autoimmune disease: association of susceptibility to
      moderate/severe endometriosis with CCL21 and HLA-DRB1.
AB  - This study investigates the association of rheumatoid arthritis-associated single
      nucleotide polymorphisms in endometriosis. We found an association of CCL21
      (rs2812378) and HLA-DRB1 (rs660895) with moderate to severe endometriosis.

PMID- 20797714
TI  - Molecular mechanisms for curcumin benefits against ischemic injury.

PMID- 20797715
TI  - The typical ovarian endometrioma has a surface origin.

PMID- 20797716
TI  - Epistasis between CYP19A1 and ESR1 polymorphisms is associated with premature
      ovarian failure.
AB  - Because an interaction between CYP19A1 and ESR1 may play a key role in
      determining the level of circulating E2 by way of the hypothalamus-hypophysis
      ovarian axis, the effect of single nucleotide polymorphism (SNP)-SNP interactions
      between CYP19A1 and ESR1 on the development of premature ovarian failure (POF)
      was investigated by comparing the polymorphisms of 98 patients with POF and 218
      matched controls of Korean ethnicity. A significant association with POF risk was
      found for the combined genetic effect between the CYP19A1 3'untranslated region
      (UTR) SNP rs10046 (CT+TT) and the intronic ESR1 SNP rs1569788 (CC) genotype (odds
      ratio=12.67, 95% confidence interval: 1.61-99.71), and a statistically
      significant association was also observed between POF and the CYP19A1 3'UTR SNP
      rs10046 under a dominant model (odds ratio=2.51, 95% confidence interval: 1.33
      4.76), suggesting that epistasis between ESR1 and CYP19A1 may be involved in the
      regulation of folliculogenesis.

PMID- 20797717
TI  - Age-specific nomogram for the decline in antral follicle count throughout the
      reproductive period.
AB  - OBJECTIVE: To investigate the relationship between antral follicle count (AFC)
      and chronological age and to establish normal values for AFC in women with
      regular menstrual cycles. DESIGN: Cross-sectional study. SETTING: University
      hospital. PATIENT(S): Four hundred fifteen premenopausal women were recruited for
      the study. Data from 362 patients were available for the statistical analysis.
      INTERVENTION(S): AFC was measured by transvaginal ultrasound examination. MAIN
      OUTCOME MEASURE(S): Estimating the relationship between AFC and age and
      developing the AFC nomogram. RESULT(S): The analysis showed a linear decline in
      AFC with age; for every year increase in age, the median AFC decreases by 0.4.
      The AFC corresponding to the 5th, 25th, 50th, 75th, and 95th centiles for each
      age have been calculated. CONCLUSION(S): A linear relationship of AFC to age was
      found. For the first time, a nomogram reporting normal and interquartile values
      for AFC, age by age, throughout the reproductive period has been provided. Until
      now, the interpretation of the measurement was mainly based on the individual
      experience of the operator, because no normative data were present. Therefore,
      the establishment of a nomogram of AFC values is the first step to counsel
      patients on a scientific basis.

PMID- 20797718
TI  - Increased plasma levels of phthalate esters in women with advanced-stage
      endometriosis: a prospective case-control study.
AB  - We performed the present prospective case-control study to evaluate whether the
      plasma concentrations of phthalate esters are elevated in women with advanced
      stage endometriosis in a Korean population. Measuring plasma levels of
      monoethylhexyl phthalate and di-(2-ethylhexyl) phthalate in 97 women with
      advanced-stage endometriosis and 169 control women by liquid chromatography
      tandem mass spectrometry, we found that the concentrations of monoethylhexyl
      phthalate, as well as di-(2-ethylhexyl) phthalate, are significantly higher in
      those with advanced-stage endometriosis, which supports the hypothesis that
      exposure to phthalate might play a role in the establishment of endometriosis.

PMID- 20797719
TI  - Analytical aspects of cyanobacterial volatile organic compounds for investigation
      of their production behavior.
AB  - In order to fully understand the role of volatile organic compounds (VOCs) under
      natural conditions, an adaptable analytical method was developed as the first
      step. beta-Ionone, beta-cyclocitral, 2-methyl-1-butanol and 3-methyl-1-butanol
      were simultaneously analyzed in addition to geosmin and 2-MIB using GC/MS with
      SPME. The slight modification of a known method allowed the simultaneous
      detection and quantification of these VOCs. The SIM of the 3-methyl-1-butanol was
      always accompanied by a shoulder peak, suggesting the presence of two compounds.
      In order to separate both compounds, the GC/MS conditions were optimized, and the
      additional peak was identified as 2-methyl-1-butanol by direct comparison of the
      authentic compound, indicating that the Microcystis strain always produces a
      mixture of 2-methyl-1-butanol and 3-methyl-1-butanol. Furthermore, it was found
      that 2-methyl-1-butanol and 3-methyl-1-butanol were predominant in the dissolved
      fractions. beta-Cyclocitral was easily oxidized to provide the oxidation product,
      2,6,6-trimethylcyclohexene-1-carboxylic acid, which causes the blue color
      formation of cyanobacteria as a consequence of acid stress. The intact acid could
      be satisfactorily analyzed using the usual GC/MS without derivatization.

PMID- 20797720
TI  - A durable PtRu/C catalyst with a thin protective layer for direct methanol fuel
      cells.
AB  - A methanol oxidation catalyst with improved durability in acidic environments is
      reported. The catalyst consists of PtRu alloy nanoparticles on a carbon support
      that were stabilized with a silane-coupling agent. The catalyst was prepared by
      reducing ions of Pt and Ru in the presence of a carbon support and the silane
      coupling agent. The careful choice of preparatory conditions such as the
      concentration of the silane-coupling agent and solution pH resulted in the
      preparation of catalyst in which the PtRu nanoparticles were dispersively
      adsorbed onto the carbon support. The catalytic activity was similar to that of a
      commercial catalyst and was unchanged after immersion in sulfuric acid solution
      for 1000 h, suggesting the high durability of the PtRu catalyst for the anode of
      direct methanol fuel cells.

PMID- 20797721
TI  - Arginine end-functionalized poly(L-lysine) dendrigrafts for the stabilization and
      controlled release of insulin.
AB  - Second generation biodegradable poly(l-lysine) dendrigrafts functionalized with
      12-48 arginine end-groups interact, at physiological pH, with insulin affording
      dendrigraft/insulin complexes as established by dynamic light scattering, zeta
      potential, circular dichroism and isothermal titration calorimetry. Binding
      occurs in two steps; at low dendrigraft/insulin molar ratios (< or = 0.07)
      interaction is accompanied with the endothermic dissociation of insulin dimers,
      while at higher molar ratios, complexation of insulin monomers with dendrigraft
      derivatives occurs exothermically. High levels of insulin complexation
      efficiencies (>99%) were determined for all derivatives. Stabilization of
      complexed insulin against enzymatic degradation by trypsin and alpha-chymotrypsin
      is observed especially for the highly arginine end-functionalized dendrigrafts.
      Insulin release rates in simulated intestinal fluid are being controlled by the
      number of arginine end-groups and released insulin retains its conformation.

PMID- 20797722
TI  - Facile controlled preparation of phosphonic acid-functionalized gold
      nanoparticles.
AB  - In the preparation and storage of gold nanoparticles (Au-NPs) in colloidal form,
      the stability of the colloid is of utmost importance. We report a novel strategy
      for the synthesis of the phosphonic acid-functionalized gold nanoparticles (Au
      NPs) with the high colloid stability by using ethylenediamine-tetramethylene
      phosphonic acid (EDTMP) as the reducing agent and its oxidation product as the
      stabilizing agent. The resultant phosphonic acid-functionalized Au-NPs show a
      remarkable colloidal stability, which likely arises from strong electrostatic
      effect of negatively charged phosphonate groups and the extremely hydrophilic
      property of phosphonate groups. Through the present method, the scope of reducing
      and stabilizing agents for preparation of phosphonic acid-functionalized Au-NPs
      extend from the -PO(3)H(2)-terminated thiols to the aminopolyphosphonates.

PMID- 20797723
TI  - Induced micellization and micellar transitions in aqueous solutions of non-linear
      block copolymer Tetronic(r) T904.
AB  - Tetronics(r) (Poloxamines) are the least studied block copolymers with an X
      shaped molecular geometry formed by four poly (propylene oxide, PPO) and poly
      (ethylene oxide, PEO) block chains, bonded to a central ethylenediamine group.
      Compared to their linear counterparts, the Pluronics, Tetronics(r) are novel, in
      that they possess superior physicochemical properties, and are relatively less
      studied. A complete understanding of their solution behavior under different
      solution conditions can make them competitive candidates for novel drug delivery
      systems. The micellization behavior and aqueous solution properties of
      Tetronic(r) T904 [(EO(15)PO(17)) (2)NCH(2)CH(2)N (PO(17)EO(15))(2)] have been
      determined by cloud point, viscosity, dynamic light scattering (DLS), small-angle
      neutron scattering (SANS), and nuclear magnetic resonance (NMR) measurements. The
      copolymer formed spherical micelles at 30 degrees C with a core radius (R(c)) of
      about 2.5 nm, a hard sphere radius (R(hs)) of 5.2 nm and an aggregation number
      (N(agg)) of 10. The effect of copolymer concentration, temperature, pH and salt
      on the micellar and phase behavior is examined. The copolymer has been found to
      exist in aggregated form only at higher pH values of >8. An increase in micelle
      size and aggregation has been observed for an increase in temperature and salt
      concentration, mainly due to the dehydration of the hydrated PEO shell. The added
      salts (NaCl, Na(2)SO(4) and Na(3)PO(4)) induce micellization and favor the
      micellar transition at lower temperatures due to the "salting out effect"; the
      effect of anions follows the Hofmeister series (PO(4)(3-)>SO(4)(2-)>Cl(-)).

PMID- 20797724
TI  - Adsolubilisation of organic compounds onto collagen fibres.
AB  - Adsolubilisation has been defined as the incorporation to solid-water interfaces
      of molecules that do not adsorb spontaneously to such interfaces, but can be
      incorporated through an interaction with an adsorbing surfactant molecule. The
      aim of this work was to study the adsolubilisation of organic molecules with
      different hydrophobicity on collagen fibres. Hide powder collagen was treated
      under mild acidic aqueous conditions with an anionic surfactant, sodium
      dodecylbenzene sulphonate. Thereafter, five different organic molecules, i.e.,
      benzyl alcohol, 2-naphtol, pararosaniline, hexamethylpararosaniline and
      nonylphenol with 10 mol ethylene oxide were separately applied to the treated
      collagen in order to study adsolubilisation as a function of their
      hydrophobicity. It was found that under acidic conditions all molecules were
      scarcely adsorbed or not adsorbed by the native hide powder collagen. However,
      all organic molecules, except benzyl alcohol, were adsolubilised if the hide
      powder collagen was previously treated with the anionic surfactant. The
      hydrophobicity of the molecules plays an important role in the adsolubilisation
      phenomenon with the result that the higher the hydrophobicity (nonylphenol with
      10 mol ethylene oxide), the higher the adsolubilisation.

PMID- 20797725
TI  - Long-term effects of prenatal omega-3 fatty acid intake on visual function in
      school-age children.
AB  - OBJECTIVE: To assess the long-term effect on visual development of omega-3
      polyunsaturated fatty acid (n-3 PUFA) intake during gestation. STUDY DESIGN:
      Using visual evoked potentials (VEPs), the long-term effects on visual
      development were evaluated in 136 school-age Inuit children exposed to high
      levels of n-3 PUFAs during gestation. VEP protocols using color and motion
      stimuli were used to assess parvocellular and magnocellular responses.
      Concentrations of the two major n-3 PUFAs (docosahexaenoic acid [DHA] and
      eicosapentaenoic acid [EPA]) were measured in umbilical cord and child plasma
      phospholipids, reflecting prenatal and postnatal exposure, respectively. RESULTS:
      After adjustment for confounders, cord plasma DHA level was found to be
      associated with shorter latencies of the N1 and P1 components of the color VEPs.
      No effects were found for current n-3 PUFA body burden or motion-onset VEPs.
      CONCLUSION: This study demonstrates beneficial effects of DHA intake during
      gestation on visual system function at school age. DHA is particularly important
      for the early development and long-term function of the visual parvocellular
      pathway.

PMID- 20797726
TI  - Glycemic control in youth with type 2 diabetes declines as early as two years
      after diagnosis.
AB  - OBJECTIVES: To determine the course of glycemic decline in a pediatric cohort
      with type 2 diabetes mellitus (T2DM) by defining longitudinal changes in
      hemoglobin A1c (HbA1c) and insulin requirement. We also followed markers of
      insulin reserve (fasting C-peptide and IGFBP-1) over time. STUDY DESIGN:
      Participants included two groups: (1) T2DM Nonacidotic (NA) (n = 46); and (2)
      T2DM diabetic ketoacidosis (n = 13). HbA1c, insulin dose, and fasting C-peptide
      and IGFBP-1 were obtained at baseline and every 6 months for 4 years. RESULTS: At
      baseline, Mann Whitney tests demonstrated that the diabetic ketoacidosis group
      had higher HbA1c (P = .002), required more insulin (P = .036), and had lower C
      peptide (P = .003) than the NA group. Baseline insulin dose (Spearman r = -0.424,
      P = .009) and baseline IGFBP-1 (Spearman r = -0.349, P = .046) correlated
      negatively with C-peptide. Over time, HbA1c, insulin dose, and C-peptide changed
      significantly in a complex manner, with group differences. HbA1c reached a nadir
      at 6 to 12 months and began to rise after 1.5 years. Insulin requirements reached
      a nadir at 1 year and began to rise after 2 years. CONCLUSIONS: Unlike adults,
      children with T2DM require increasing insulin doses over a 4-year period, and
      diabetic ketoacidosis at diagnosis predicts greater beta-cell decline over time.

PMID- 20797727
TI  - Age at onset of puberty predicts bone mass in young adulthood.
AB  - OBJECTIVE: To determine whether the commencement and length of puberty influences
      dual x-ray absorptiometry (DXA) values of bone mineral content (BMC) and bone
      mineral density (BMD) in the axial and appendicular skeleton at skeletal
      maturity. STUDY DESIGN: From the Bone Mineral Density in Childhood Study, we
      identified children who began puberty and completed sexual and skeletal
      development and examined whether the timing and length of puberty influence DXA
      values of BMC and BMD at skeletal maturity. RESULTS: A total of 78 girls and 85
      boys began puberty and completed skeletal maturity; 4.4 +/- 0.8 and 4.5 +/- 0.8
      years later, respectively. Multiple linear regression analyses indicated that the
      age of onset of puberty was a strong negative predictor of DXA bone measurements
      at skeletal maturity, independent of bone values at the beginning of puberty, and
      the length of puberty. This negative relation was observed for all BMC and BMD
      measurements at all skeletal sites, in both boys and girls (all P < .0001). In
      contrast, length of puberty had no relation to any measures of bone. CONCLUSIONS:
      In healthy adolescent males and females, bone mass and bone density at skeletal
      maturity are inversely related to the timing of puberty.

PMID- 20797728
TI  - Endocrine dysfunction following traumatic brain injury in children.
AB  - OBJECTIVE: To identify the incidence of endocrine dysfunction in children
      following traumatic brain injury (TBI). STUDY DESIGN: This was a prospective
      evaluation of 31 children after TBI. Inclusion criteria included Glasgow Coma
      Scale score <= 12 and age 1.5-18 years. We evaluated thyroid function, insulin
      like growth factor I, insulin-like growth factor-binding protein 3, and cortisol
      at 1, 3, 6, and 12 months after injury, and assessed prolactin at 3 and 6 months.
      At 6 months, we also assessed overnight spontaneous growth hormone secretion,
      nocturnal thyrotropin surge, adrenal reserve, and serum and urine osmolarity.
      RESULTS: The average patient age was 11.6 years, and mean Glascow Coma Scale
      score was 6. The incidence of endocrine dysfunction was 15% at 1 month, 75% at 6
      months, and 29% at 12 months. At 12 months after injury, 14% had precocious
      puberty, 9% had hypothyroidism, and 5% had growth hormone deficiency. Endocrine
      dysfunction at 1 year did not correlate with the severity of injury. CONCLUSIONS:
      Endocrine dysfunction after TBI is common in children, but most cases resolve by
      1 year. We recommend endocrine surveillance at both 6 and 12 months following
      moderate or severe TBI to ensure early intervention for persistent or late
      occurring endocrine sequelae.

PMID- 20797729
TI  - Validation of upper extremity post-thrombotic syndrome outcome measurement in
      children.
AB  - Using the Manco-Johnson instrument in a derivation cohort of 107 children with or
      without a central venous catheter, upper extremity physical findings of post
      thrombotic syndrome were absent, and the pain score was 0 in all but one child.
      Interrater reliability in an independent validation cohort (n = 38) of children
      with or without upper extremity deep venous thrombosis was 97%-100%.

PMID- 20797732
TI  - Analgesic effect of bupivacaine eluting porcine small intestinal submucosa (SIS)
      in ferrets undergoing acute abdominal hernia defect surgery.
AB  - BACKGROUND: Porcine small intestinal submucosa (SIS) is used as a biological
      implant for abdominal wall hernia repair to facilitate wound healing and augment
      local tissue strength. This prospective, randomized, blinded study evaluated
      local pain control provided by bupivacaine adsorbed to SIS for repair of acutely
      created abdominal wall full thickness muscle/fascial defects in ferrets.
      MATERIALS AND METHODS: Eighteen healthy ferrets were randomly and equally
      assigned to three groups: (1) SIS with bupivacaine subjected to surgery, (2) SIS
      with no bupivacaine subjected to surgery, and (3) anesthesia only control group.
      Ferrets in groups 1 and 2 were anesthetized with butorphanol and sevoflurane for
      the surgery. Control ferrets were anesthetized in the same fashion for the same
      duration without surgery. Behavior and pain were evaluated in all ferrets by
      behavioral observation, algometer, and palpometer measurements, and heart and
      respiratory rates each obtained before surgery and at various intervals for 96 h
      after surgery. When pain reached a predetermined threshold, buprenorphine was
      used as a rescue analgesic. The serum and combined tissue concentrations of
      bupivacaine were analyzed. RESULTS: Overall, the palpometer testing was better
      tolerated in the bupivacaine treated SIS group than by the untreated SIS group (P
      = 0.04). There was an observed physiologically significant difference in
      algometer and other palpometer readings as well as heart and respiratory rates.
      All ferrets in the untreated SIS group were rescued while 33% of the SIS
      bupivacaine groups were rescued (P < 0.01). Peak serum concentrations of
      bupivacaine were in the range of 0.7 MUg/mL with tissue level below detection
      levels and no clinical signs of toxicity were observed. CONCLUSIONS: Bupivacaine
      adsorbed to SIS provided some degree of pain relief over 2-4 days with no
      clinical adverse effects observed in the ferrets.

PMID- 20797731
TI  - Thalamic morphology in schizophrenia and schizoaffective disorder.
AB  - BACKGROUND: Biomarkers are needed that can distinguish between schizophrenia and
      schizoaffective disorder to inform the ongoing debate over the diagnostic
      boundary between these two disorders. Neuromorphometric abnormalities of the
      thalamus have been reported in individuals with schizophrenia and linked to core
      features of the disorder, but have not been similarly investigated in individuals
      with schizoaffective disorder. In this study, we examine whether individuals with
      schizoaffective disorder have a pattern of thalamic deformation that is similar
      or different to the pattern found in individuals with schizophrenia. METHOD: T1
      weighted magnetic resonance images were collected from individuals with
      schizophrenia (n = 47), individuals with schizoaffective disorder (n = 15), and
      controls (n = 42). Large-deformation, high-dimensional brain mapping was used to
      obtain three-dimensional surfaces of the thalamus. Multiple analyses of variance
      were used to test for group differences in volume and measures of surface shape.
      RESULTS: Individuals with schizophrenia or schizoaffective disorder have similar
      thalamic volumes. Thalamic surface shape deformation associated with
      schizophrenia suggests selective involvement of the anterior and posterior
      thalamus, while deformations in mediodorsal and ventrolateral regions were
      observed in both groups. Schizoaffective disorder had distinct deformations in
      medial and lateral thalamic regions. CONCLUSIONS: Abnormalities distinct to
      schizoaffective disorder suggest involvement of the central and ventroposterior
      medial thalamus which may be involved in mood circuitry, dorsolateral nucleus
      which is involved in recall processing, and the lateral geniculate nucleus which
      is involved in visual processing.

PMID- 20797734
TI  - Dr. Bernard Churchill.

PMID- 20797733
TI  - Safety and outcome after thrombolytic treatment in ischemic stroke patients with
      high-risk cardioembolic sources and prior subtherapeutic warfarin use.
AB  - BACKGROUND: Hemorrhage is a major complication of thrombolytic treatment.
      Concerns have been raised about the risk of hemorrhage in patients having
      received warfarin. Therefore, different indications for thrombolytic treatment
      are in use for stroke patients on warfarin. However, it remains uncertain whether
      the prior warfarin use actually increases their risk of bleeding in patients
      treated with thrombolysis. METHODS: This study included 179 consecutive patients
      who had high-risk cardioembolic sources and received thrombolytic treatment.
      Patients were treated with intravenous thrombolytic agents, or underwent
      intraarterial thrombolysis if their international normalized ratio (INR) was
      <=1.7. We compared the frequency of bleeding complications between patients with
      prior warfarin use and those without. We also investigated whether there were
      differences in functional outcome and recanalization rates between them. RESULTS:
      A prior warfarin use was present in 28 patients (15.6%). Although INR levels were
      higher in the prior warfarin group, the frequency of bleeding complications was
      not different between patients who received prior warfarin and those who did not.
      No differences were observed in patients with or without prior warfarin use, for
      successful recanalization rate (Thrombolysis in Myocardial Infarction grade 2 or
      3), mortality, or modified Rankin score (<=2) at 3months. CONCLUSIONS:
      Thrombolytic therapy for patients who previously received warfarin and had an
      INR<=1.7 did not affect bleeding risk, clinical outcome, or recanalization rate.
      Our data suggest that patients with a history of prior warfarin use may be safely
      treated with thrombolytic agents when their INR levels are low.

PMID- 20797730
TI  - Social appraisal in chronic psychosis: role of medial frontal and occipital
      networks.
AB  - Persons with schizophrenia often appraise other individuals as threatening or
      persecutory. To evaluate social appraisal in schizophrenia, we probed brain
      networks with a task in which subjects judged whether or not they liked face
      stimuli with emotional expressions. We predicted that appraising negative
      expressions would engage patients, more than controls, and negative faces would
      be related to higher levels of negative affect and produce increased activity in
      the medial frontal cortex, an area involved in social appraisal. Twenty-one
      stable outpatients with chronic non-affective psychosis (16 schizophrenic, 5
      schizoaffective) and 21 healthy subjects underwent functional magnetic resonance
      imaging. Compared with the control subjects, patients were slower to respond, but
      particularly slow when they judged negatively-valenced faces, a slowness
      correlated with negative affect in the psychosis patients. Appraisal activated
      the medial prefrontal cortex (mPFC) across all face valences. For negative
      expressions, patients exhibited greater activation of the dorsal anterior
      cingulate cortex (dACC). A psychophysiological interaction analysis of the dACC
      revealed co-modulation of the mPFC in controls, significantly less in patients,
      and a trend for co-modulation of occipital cortex in the patients. Activity in
      occipital cortex correlated with poor social adjustment and impaired social
      cognition, and co-modulation of the occipital gyrus by the dACC was correlated
      with poorer social cognition. The findings link appraisal of negative affect with
      aberrant activation of the medial frontal cortex, while early sensory processing
      of this social cognitive task was linked with poor social function, reflecting
      either top-down or bottom-up influences.

PMID- 20797735
TI  - Extent and frequency of vessel oil spills in US marine protected areas.
AB  - Little is known about how marine protected areas (MPAs) may be vulnerable to
      vessel oil spills in the United States. This study investigated individual size,
      frequency, and total amount of vessel oil spilled in US MPAs, and how
      characteristics of MPAs and individual spill events influenced spills. Vessel oil
      spills in US waters (2002-06) and MPA boundaries were mapped. Total number and
      volume of oil spills inside and outside MPAs were computed. Results show that the
      presence of a MPA does not seem to prevent vessel oil spills or reduce the amount
      of oil spilled, and that a variety of MPA attributes (e.g., scale of protection,
      fishing restrictions, and others) and spill event characteristics (e.g., vessel
      type, year of spill, and others) affect oil spills inside and outside MPAs. These
      results can be used to develop MPA rules and marine transportation policies that
      reduce the vulnerability of sensitive resources to oil spills.

PMID- 20797736
TI  - Limonoids from the seeds of a Godavari mangrove, Xylocarpus moluccensis.
AB  - Ten limonoids, named godavarins A-J (1-7, 9-11), were isolated from seeds of an
      Indian mangrove (Xylocarpus moluccensis) collected in the mangrove wetlands of
      Godavari estuary, Andhra Pradesh. Eight known limonoids, viz. xyloccensins L (8),
      P (12), Q (13), mexicanolide (14), 6-deoxy-3-detigloyl-swietenine acetate (15),
      fissinolide (16), methyl 3beta-acetoxy-1-oxomeliaca-8(30),14-dienoate (17), and
      methyl 3beta-acetoxy-1-oxomeliaca-8(9),14-dienoate (18), were also obtained. The
      structures of these compounds were established on the basis of spectroscopic data
      or comparison with data in the literature (known compounds). The stereostructure
      of godavarin D was confirmed by means of single-crystal X-ray analysis.
      Godavarins A-C are the first mexicanolide derivatives with a C7-C28 ester-linked
      delta-lactone ring, while godavarins D-G are further additions to the small group
      of limonoids with a C1-C29 oxygen bridge. Godavarin H is a phragmalin with five
      acetoxy groups. Two limonoids, mexicanolide and fissinolide, were found to
      exhibit marked antifeedant activity against the third-instar larvae of Brontispa
      longissima (Gestro) at a concentration of 0.5 mg/mL. The most potent compound was
      mexicanolide. It also showed moderate insecticidal activity.

PMID- 20797737
TI  - Synergetic effects of oral administration of levamisole and Echinacea purpurea on
      immune response in Wistar rat.
AB  - This research investigated the effects of levamisole and Echinacea purpurea (EP),
      separately and together on the immune response of the rat as a laboratory model.
      In this experiment, 40 male Wistar rats were obtained and divided into four
      groups (n=10). These groups received normal saline (10 mg/kg), EP (500 mg/kg),
      levamisole (2 mg/kg) and EP (500 mg/kg) with levamisole (2 mg/kg) as oral gavages
      every day for a period of 4 weeks, respectively. After obtaining blood samples
      (at the end of each week), haematocrit (HCT), differential and total white blood
      cell (WBC) counts, phagocyte activity (number), total protein, albumin and
      globulins levels of samples were obtained. The results of the study showed that
      the gamma globulin level, WBC, neutrophil and monocyte counts and phagocyte
      activity increased significantly in comparison with normal saline group during
      the study. According to the results, each of the mentioned agents had a stimulant
      effect on the immune system separately and together on rats. In the group that
      received EP and levamisole simultaneously, these effects were synergistically
      increased. These compounds, by increasing the mentioned factors, will probably
      affect the immune system.

PMID- 20797738
TI  - Molecular characterization of Mycobacterium tuberculosis complex (MTBC) isolated
      from cattle in northeast and northwest China.
AB  - We studied throat swabs and corresponding serum samples collected from 1067
      protein purified derivative (PPD)-tuberculin skin test (TST) positive cattle from
      different regions of China. The 1067 throat swabs were inoculated onto modified
      Lowenstein-Jensen medium for the isolation and culture of Mycobacteria. Acid-fast
      bacilli were identified using traditional biochemical methods, polymerase chain
      reaction (PCR) amplification and multiplex PCR. They were distinguished as
      Mycobacterium tuberculosis complex (MTBC) and non-tuberculous mycobacteria (NTM)
      strains. An indirect Enzyme-Linked Immunosorbent Assay (ELISA) was applied to
      detect specific antibodies against bovine TB (bTB). Correlations among the ELISA,
      bacteriology and TST were analyzed and compared. Spoligotyping and variable
      number tandem repeats-mycobacterial interspersed repetitive unit (VNTR-MIRU)
      analysis were used to genotype the MTBC. In total, 111 strains of Mycobacteria
      were cultured from the 1067 throat swab samples, including 43 stains of MTBC (14
      strains of Mycobacterium bovis and 29 of Mycobacterium tuberculosis) and 68
      strains of NTM. Thirty-eight MTBC strains and four NTM strains were isolated from
      72 throat swab samples that the ELISA determined were antibody positive; five
      MTBC strains and 64 NTM strains were isolated from 995 throat swab samples that
      were antibody negative on the ELISA. The positive isolation rates of MTBC and NTM
      were 38.7% (43/111) and 61.3% (68/111), respectively. The concordance rate of
      cultured MTBC with a positive result on the indirect ELISA for antibody was 52.8%
      (38/72), which was much higher than the positive rate for TST (4.0%; 43/1067).
      Genotyping of the 43 strains of MTBC isolated, using spoligotyping and VNTR-MIRU,
      showed that the 43 isolates had 26 genotypes; 16 strains had a unique genotype.
      Two groups of six strains and two strains, respectively, showed the same
      spoligotyping pattern, and belonged to the Beijing family and Beijing-like
      family, respectively. Combined application of spoligotyping and VNTR-MIRU typing
      would improve the molecular epidemiological investigation and monitoring of the
      etiology of bTB in China.

PMID- 20797739
TI  - Chronic frontal sinus disease: combined use of platelet-rich plasma and calvarial
      bone grafts for sinus obliteration in aggressive and secondary cases.
AB  - INTRODUCTION: The surgical management of chronic frontal sinusitis can be
      challenging. The most effective way to treat this condition is sinus
      obliteration. Several methods have been published. We evaluated the feasibility
      of a combined treatment, consisting of platelet-rich plasma (PRP) and autologous
      calvarial bone chips, in chronic frontal sinus diseases (CFSD). PATIENTS AND
      METHODS: From January 2001 to June 2006, seven patients (four women and three
      men) were admitted presenting with signs and symptoms of CFSD. Their ages ranged
      from 35 to 67 years. Two patients presented with signs of frontal osteomyelitis
      and a cutaneous fistula, while endoscopic drainage had failed for five patients.
      All patients were treated by sinus obliteration though bicoronal access. Free
      autologous calvarial bone graft combined with PRP was used to repair the frontal
      sinus. RESULTS: The frontal sinus repair was successful in all seven patients
      with progressive resolution of symptoms without perioperative complication. The
      CT scans at 12 postoperative months showed complete obliteration of sinuses.
      DISCUSSION: Combined PRP and autologous bone graft is a safe and reliable
      procedure for frontal sinus obliteration. The low rate of complications and the
      absence of donor site morbidity support using this technique in secondary and
      particularly complex cases.

PMID- 20797740
TI  - [Risk of caries in orthodontics: descriptive study on 155 patients].
AB  - INTRODUCTION: The aim of this survey was to study the prevalence of tooth decay,
      to assess oral hygiene control, to analyze the different risk factors for caries
      in orthodontics, and to determine recommendations. PATIENTS AND METHODS: We
      studied 155 patients managed in the unit, for three months and 19 days. The main
      indicators used were: the DMF index; Loe and Silness's gingival index, and
      Silness and Loe's plate index. RESULTS: The plate index ranged between 0.08 and
      2.4, with a mean of 1.12 +/- 0.48; the gingival index ranged between 0 and 2,
      with a mean of 0.67 +/- 0.43; the DMF index ranged between 0 and 21, with a mean
      of 5.77 +/- 4.52. DISCUSSION: The orthodontist has a major role to play in the
      prevention of caries before and after treatment. Recommendations and patient
      information should be adapted to risk for dental caries.

PMID- 20797741
TI  - [Screening and diagnosis of precancerous oral mucosa lesions].
AB  - The screening and early diagnosis of cancerous oral mucosa lesions are still key
      elements for a better prognosis. Therefore, it is of tremendous importance to try
      to determine how and when to diagnose precancerous oral mucosa lesions. Usually,
      clinical examination data must be completed by a pathological examination. This
      study, based on an exhaustive literature review, has for purpose to determine the
      sensitivity and specificity of complementary diagnostic tools currently
      available.

PMID- 20797742
TI  - [Meningoencephalitis caused by Rickettsia conorii in a young infant].
AB  - INTRODUCTION: Mediterranean spotted fever is an infectious disease due to
      Rickettsia conori, endemic in the Mediterranean basin. It is usually considered
      to be a benign disease; however, severe systemic manifestations have been
      reported in which neurological involvement occurs. These complications are rare
      in children. CASE REPORT: We report a case of a 14-month-old boy, who was
      hospitalized for meningoencephalitis after seven days of high fever and
      maculopapular rash. On clinical observation there were generalized maculopapular
      elements and an inoculation eschar tache noire at the right ear. The diagnosis of
      Mediterranean spotted fever was established by epidemiological and clinical
      features and was confirmed by elevated IgM antibody titres against R. conorii by
      indirect immunofluorescence assay. Despite treatment with macrolides and
      corticosteroids, severe neurological sequelae have remained including decreased
      vision and epileptic seizures. CONCLUSION: The physiopathology of Mediterranean
      spotted fever includes diffuse vasculitis with endothelial injury. Early
      diagnosis and specific antibiotic treatment may reduce the risk of complications.

PMID- 20797743
TI  - Pancreatic surgery: evolution at a high-volume center.
AB  - BACKGROUND: Advances in imaging, minimally invasive techniques, and
      regionalization have changed pancreatic surgery. Therefore, the aims of this
      report are to determine whether the pancreatic operations or the spectrum of
      disease have evolved at a high-volume center. METHODS: From 1996 through 2009,
      2,004 pancreatic operations were performed at Indiana University Hospital. The
      operations, pathology, and outcomes for 1996-2003 were compared with 2004-2009.
      RESULTS: In 2004-2009, more operations/year were performed (215 vs 89; P < .01)
      and patients were older (58.8 years vs 55.8 years; P < .01). In recent years,
      more pancreatoduodenectomies (55.0% vs 50.4%) and fewer pancreatojejunostomies
      (6.2% vs 12.6%) and Beger/Frey procedures (2.6% vs 4.8%) were performed (P <
      .05). In 2004-2009, pylorus preservation (81.1% vs 64.4%), laparoscopic distal
      pancreatectomy (33.9% vs 0%), and splenic preservation (25.3% vs 2.2%) were
      carried out more frequently (P < .001). Pathology review revealed more tumors
      (68.8% vs 60.4%) and less pancreatitis (29.2% vs 34.4%; P < .01). Thirty-day
      mortality improved from 2.5% to 1.8%. CONCLUSION: At a high-volume pancreatic
      surgery center, the number and age of the patients, the percentage of pancreatic
      resections, preservation of the pylorus and spleen as well as laparoscopic
      procedures, and the percentage of patients with tumors all have increased,
      whereas the outcomes continued to improve.

PMID- 20797744
TI  - Industrial relations with academic health care and professional medical
      associations: what's all the fuss? Who cares anyway?

PMID- 20797745
TI  - Comparison of outcomes after laparoscopic versus open appendectomy for acute
      appendicitis at 222 ACS NSQIP hospitals.
AB  - BACKGROUND: The benefit of laparoscopic (LA) versus open (OA) appendectomy,
      particularly for complicated appendicitis, remains unclear. Our objectives were
      to assess 30-day outcomes after LA versus OA for acute appendicitis and
      complicated appendicitis, determine the incidence of specific outcomes after
      appendectomy, and examine factors influencing the utilization and duration of the
      operative approach with multi-institutional clinical data. METHODS: Using the
      American College of Surgeons National Surgical Quality Improvement Program (ACS
      NSQIP) database (2005-2008), patients were identified who underwent emergency
      appendectomy for acute appendicitis at 222 participating hospitals. Regression
      models, which included propensity score adjustment to minimize the influence of
      treatment selection bias, were constructed. Models assessed the association
      between surgical approach (LA vs OA) and risk-adjusted overall morbidity,
      surgical site infection (SSI), serious morbidity, and serious
      morbidity/mortality, as well as individual complications in patients with acute
      appendicitis and complicated appendicitis. The relationships between operative
      approach, operative duration, and extended duration of stay with hospital
      academic affiliation were also examined. RESULTS: Of 32,683 patients, 24,969
      (76.4%) underwent LA and 7,714 (23.6%) underwent OA. Patients who underwent OA
      were significantly older with more comorbidities compared with those who
      underwent LA. Patients treated with LA were less likely to experience an overall
      morbidity (4.5% vs 8.8%; odds ratio [OR], 0.60; 95% confidence interval [CI],
      0.54-0.68) or a SSI (3.3% vs 6.7%; OR, 0.57; 95% CI, 0.50-0.65) but not a serious
      morbidity (2.6% vs 4.2%; OR, 0.86; 95% CI, 0.74-1.01) or a serious
      morbidity/mortality (2.6% vs 4.3%; OR, 0.87; 95% CI, 0.74-1.01) compared with
      those who underwent OA. All patients treated with LA were significantly less
      likely to develop individual infectious complications except for organ space SSI.
      Among patients with complicated appendicitis, organ space SSI was significantly
      more common after laparoscopic appendectomy (6.3% vs 4.8%; OR, 1.35; 95% CI, 1.05
      1.73). For all patients with acute appendicitis, those treated at academic
      affiliated versus community hospitals were equally likely to undergo LA versus OA
      (77.0% vs 77.3%; P = .58). Operative duration at academic centers was
      significantly longer for both LA and OA (LA, 47 vs 38 minutes [P < .0001]; OA, 49
      vs 44 minutes [P < .0001]). Median duration of stay after LA was 1 day at both
      academic-affiliated and community hospitals. CONCLUSION: Within ACS NSQIP
      hospitals, LA is associated with lower overall morbidity in selected patients.
      However, patients with complicated appendicitis may have a greater risk of organ
      space SSI after LA. Academic affiliation does not seem to influence the operative
      approach. However, LA is associated with similar durations of stay but slightly
      greater operative times than OA at academic versus community hospitals.

PMID- 20797746
TI  - Impact of standardized trauma documentation to the hospital's bottom line.
AB  - BACKGROUND: The dichotomy between clinical and hospital revenue generation for
      trauma care is well established. Many trauma programs require hospital support
      for fiscal survival. We evaluated the impact of standardized clinical
      documentation to the hospital's bottom line at our trauma center. METHODS:
      Standardized documentation templates for evaluation and management were created
      with a focus on accuracy and efficiency. Documentation was completed jointly by
      residents and faculty following standard guidelines of linkage. Trauma service
      characteristics, case mix index, reimbursement rate, payer distribution, hospital
      charges, cost, and payments were compared before and after standardization.
      Professional revenue was not evaluated. Analysis was performed using a
      commercially available spreadsheet computer application. RESULTS: A 24% increase
      in the hospital's net income for trauma care, constituting $1.45 million, was
      realized despite a 12% decrease in patient volume. Admission profitability
      increased by 42%. Collection rates and payer mix were unchanged. Increases in
      both injury severity score and case mix index were seen (P < .05) after
      implementation of the program. Length of stay was decreased significantly.
      CONCLUSION: An effective standardized documentation strategy for trauma care
      results in significant fiscal gains in hospital reimbursement.

PMID- 20797747
TI  - Clinical framework to guide operative decision making in disconnected left
      pancreatic remnant (DLPR) following acute or chronic pancreatitis.
AB  - BACKGROUND: Disconnected left pancreatic remnant (DLPR) presents clinically as a
      pancreatic fistula, pseudocyst, or obstructive pancreatitis. Optimal operative
      treatment, either distal pancreatectomy (DP) or internal drainage (ID), remains
      unknown. This paper critically evaluates our operative experience in patients
      with DLPR. METHODS: A retrospective analysis of a consecutive case series from a
      single, high-volume institution was carried out. A total of 76 patients with
      radiographic-confirmed DLPR (computed tomography + endoscopic retrograde
      cholangiopancreatography or magnetic resonance cholangiopancreatography) who had
      operations between November 1995 and September 2008 were included. Pancreas
      preservation (the use of ID) was our default unless anatomic, physiologic, or
      technical factors precluded it. Follow-up to July 2009 was done (median follow
      up, 22 months). Standard statistical methodology was used (P < .05 = statistical
      significance). RESULTS: The mean age of this cohort was 52 years (range, 18-85);
      57% of the patients were male. A total of 59 (73%) had acute pancreatitis,
      whereas 17 (22%) had chronic pancreatitis. Presentation was pseudocyst in 53%,
      pancreatic fistula in 34%, and obstructive pancreatitis in 13%. Resection (DP)
      and drainage (ID) options were utilized equally for each clinical presentation as
      follows: pseudocyst, 60/40; pancreatic fistula, 50/50; or obstructive
      pancreatitis, 50/50. The strongest driver for DP (92%) was a small pancreatic
      remnant and splenic vein thrombosis. In contrast, large pancreatic remnants had
      ID 70% of the time. No differences in short- or long-term outcomes between DP or
      ID options were identified. CONCLUSION: Using anatomic, physiologic, and
      technical factors to guide operative choice in DLPR, we report a 74% success rate
      with DP and an 82% success rate with ID at a median follow-up of 22 months. A
      pancreatic remnant size >6 cm favored ID options over resection.

PMID- 20797748
TI  - Robotic distal pancreatectomy: cost effective?
AB  - BACKGROUND: Minimally invasive techniques and even robotics in pancreaticobiliary
      surgery are being used increasingly. Cost-effectiveness is a practical burden
      associated with the introduction of surgical innovation. This study compares the
      costs and the outcomes of open, laparoscopic, and robotic distal
      pancreatectomies. We hypothesized that robotic distal pancreatectomy is cost
      effective. METHODS: Between August 2008 and August 2009, 77 distal
      pancreatectomies were performed at a single academic medical center. A
      retrospective analysis of prospectively collected data on demographics, short
      term outcomes, and direct cost was performed. RESULTS: Thirty-two open distal
      pancreatectomies, 28 laparoscopic distal pancreatectomies, and 17 robotic distal
      pancreatectomies were performed. Age, American Society of Anesthesia preoperative
      risk score, and specimen length were similar. Indications for laparoscopic distal
      pancreatectomies and robotic distal pancreatectomies included more cystic
      neoplasms (49%) and fewer malignancies (29%) versus open distal pancreatectomies
      (16% and 47%). Spleen preservation occurred in 65% robotic distal
      pancreatectomies versus 12% and 29% in open distal pancreatectomies and
      laparoscopic distal pancreatectomies (P < .05). The operative time averaged 298
      minutes in robotic distal pancreatectomies versus 245 and 222 minutes in open
      distal pancreatectomies and laparoscopic distal pancreatectomies (P < .05). Blood
      loss and morbidity were similar with no mortality. The length of stay was 4 days
      in robotic distal pancreatectomies versus 8 and 6 in open distal pancreatectomies
      and laparoscopic distal pancreatectomies (P < .05). The total cost was $10,588 in
      robotic distal pancreatectomies versus $16,059 and $12,986 in open distal
      pancreatectomies and laparoscopic distal pancreatectomies. CONCLUSION: These data
      suggest direct hospital costs are comparable among all groups. They suggest a
      shorter length of stay in robotic versus laparoscopic or open approaches.
      Finally, spleen and vessel preservation rates may improve with a robotic approach
      at the expense of increased operative time. In summary, robotic distal
      pancreatectomy is safe and cost effective in selected cases.

PMID- 20797749
TI  - Pancreatic cyst aspiration analysis for cystic neoplasms: mucin or
      carcinoembryonic antigen--which is better?
AB  - BACKGROUND: Differentiation between the various pathologies presenting as a
      cystic pancreatic lesion is clinically important but often challenging. We have
      previously advocated the performance of endoscopic ultrasound (EUS) with
      aspiration and determination of mucin and carcinoembryonic antigen (CEA) content.
      We sought to report the results of this ongoing protocol and determine the
      relative importance of cyst fluid mucin and CEA for the diagnostic process.
      METHODS: The institutions prospectively maintained pancreatic cyst database was
      accessed to identify patients who had undergone pancreatic EUS and cyst
      aspiration as part of their evaluation. Only those patients who had subsequently
      undergone resection were selected, with histopathology being the gold standard
      for comparison. RESULTS: From January 2000 to July 2009, 174 patients with
      pancreatic cystic disease underwent surgery, 121 of whom had an EUS with
      aspiration attempted at our institution with specimens sent for mucin and CEA.
      Based on histopathology, 86 mucinous lesions were identified, including 44
      cystadenomas, 34 intraductal papillary mucinous neoplasms, 7 mucinous
      adenocarcinomas, and 1 intraductal oncocytic papillary neoplasm; 42 were
      nonmucinous lesions. The median cyst CEA levels were significantly higher in the
      mucinous lesions group at 850 versus 2 ng/mL (P = .001). The sensitivity,
      specificity, positive predictive value (PPV), negative predictive value (NPV),
      positive diagnostic likelihood ratio, and negative diagnostic likelihood ratio
      (NDLR) were calculated respectively for mucin alone (0.80, 0.40, 0.61, 0.63,
      1.33, 0.68); CEA alone (0.93, 0.43, 0.51, 0.91, 1.63, 0.16); cytology alone
      (0.38, 0.9, 0.92, 0.31, 3.67, 0.69); mucin or CEA (0.83, 0.65, 0.87, 0.57, 2.51,
      0.26); mucin or CEA or cytology (0.92, 0.52, 0.86, 0.68, 1.91, 0.15); mucin plus
      CEA (0.96, 0.34, 0.25, 0.97, 1.45, 0.12); mucin plus cytology (0.25, 0.97, 0.96,
      0.29,7.25, 0.78); CEA plus cytology (0.12, 1.00, 1.00, 0.26, infinity, 0.88); and
      mucin plus CEA plus cytology (0.08, 1.00, 1.00, 0.25, infinity, 0.92).
      CONCLUSION: Assessment of cyst mucin and CEA are complementary, with the best
      profile obtained when both markers are determined along with cytology. This
      combination provides a good sensitivity, PPV, and NDLR, as well as reasonable PPV
      and PDNR.

PMID- 20797750
TI  - Multicenter analysis of diaphragm pacing in tetraplegics with cardiac pacemakers:
      positive implications for ventilator weaning in intensive care units.
AB  - BACKGROUND: Diaphragm pacing (DP) can replace mechanical ventilation in
      tetraplegics and in trials has assisted respiration in amyotrophic lateral
      sclerosis patients. This report describes results of DP in patients with cardiac
      pacemakers. METHODS: Prospective, single-center and multicenter, nonrandomized,
      controlled, interventional protocols under U.S. Food and Drug Administration
      and/or institutional review board approval were evaluated. Patients underwent
      laparoscopic diaphragm motor point mapping to identify optimal electrode site for
      implantation. With diaphragm conditioning, patients were weaned from their
      ventilator. Perioperative and long-term assessments between the cardiac
      pacemakers and DP were analyzed for any device-to-device interactions. RESULTS:
      Over 300 subjects were implanted from 2000 to 2010. Twenty tetraplegics with
      cardiac pacemakers and DP were analyzed from 6 sites. Subjects ranged from 19 to
      61 years old with DP implantation 6 months to 24 years postinjury. There were no
      immediate or long-term device to device interactions. All patients achieved
      diaphragm-paced tidal volumes exceeding their basal requirements and, after
      conditioning, all patients could go >4 hours without mechanical ventilators; 71%
      could go 24 hours continuously. CONCLUSION: DP can be safely implanted in
      tetraplegics having cardiac pacemakers. Applications for temporary use of DP to
      maintain diaphragm type 1 muscle fiber and improve posterior lobe ventilation may
      benefit complex critical care patients.

PMID- 20797751
TI  - Expression of the sonic hedgehog pathway molecules in synchronous follicular
      adenoma and papillary carcinoma of the thyroid gland in predicting malignancy.
AB  - BACKGROUND: Recent studies have shown that the Sonic Hedgehog pathway plays an
      important role in tumorigenesis and cancer proliferation. The Sonic Hedgehog
      pathway is required for normal thyroid gland development, but when activated as a
      result of gene mutation or overexpression, it may stimulate thyroid tumor cell
      proliferation. This study determines whether 3 molecules, Patched, Smoothened,
      and Sonic Hedgehog, involved in the Sonic Hedgehog pathway are overexpressed
      equally in synchronous follicular thyroid adenoma and papillary thyroid
      carcinoma. METHODS: Eighteen patients with synchronous follicular thyroid adenoma
      and papillary thyroid carcinoma underwent thyroidectomy. Immunohistochemistry was
      performed on the paraffin-embedded tissue to detect expression of Patched,
      Smoothened, and Sonic Hedgehog in both tumor types. The expression in these
      neoplasms was graded by 2 observers. RESULTS: Five patients had insufficient
      tumor tissue and were removed from the analysis. Patched expression was detected
      in 5 of 13 (38%) follicular adenomas and 5 of 12 (42%) papillary carcinomas.
      Smoothened was expressed in 4 of 13 (31%) follicular adenomas and 3 of 13 (23%)
      papillary carcinomas. Sonic Hedgehog was expressed in 4 of 13 (31%) follicular
      adenomas and 11 of 13 (85%) papillary carcinomas. CONCLUSION: Expression of the 3
      molecules involved in the Sonic Hedgehog pathway was similar in follicular
      thyroid adenoma, but Sonic Hedgehog expression was a more sensitive indicator of
      malignancy in papillary thyroid carcinoma. The Sonic Hedgehog molecule may become
      a diagnostic marker when the cytologic or histologic features are not
      characteristic of a papillary carcinoma. Greater understanding of the Sonic
      Hedgehog pathway may provide molecular methods for preventing or treating
      papillary thyroid carcinoma.

PMID- 20797752
TI  - Genetic analysis of small ruminant lentiviruses following lactogenic
      transmission.
AB  - Lactogenic transmission plays an important role in the biology of lentiviruses
      such as HIV and SIV or the small ruminant lentiviruses (SRLV). In this work we
      analyzed the characteristics of viruses that goats, naturally infected with two
      strains of SRLV, transmitted to their kids. The spectrum of viral genotypes
      transmitted was broader and the efficiency of transmission greater compared to
      their human and simian counterparts. The newly described A10 subgroup of SRLV was
      more efficiently transmitted than the B1 genotype. The analysis of a particular
      stretch of the envelope glycoprotein encompassing a potential neutralizing
      epitope revealed that, as in SIV, the transmitted viruses were positively charged
      in this region, but, in contrast to SIV, they tended to lack a glycosylation site
      that might protect against antibody neutralization. We conclude that the
      physiology of the ruminant neonatal intestine, which permits the adsorption of
      infected maternal cells, shaped the evolution of these particular lentiviruses
      that represent a valid model of lactogenic lentivirus transmission.

PMID- 20797754
TI  - Neutralizing antibodies to human and simian adenoviruses in humans and New-World
      monkeys.
AB  - Vaccines based on adenovirus (Ad) vectors are currently in development against
      several pathogens. However, neutralizing antibodies (NAb) to human adenovirus
      type 5 (AdHu5), the best-studied vector, are highly prevalent in humans
      worldwide. Less-prevalent adenoviruses, including human and simian serotypes,
      provide alternative vaccine platforms. In this study, sera from 200 Brazilian
      human subjects and New-World monkeys were tested for NAb titers to human
      serotypes AdHu5 and AdHu26 and chimpanzee-origin Ad viruses of serotype 6 (AdC6)
      and serotype 68 (AdC68). Seroprevalence rates of NAb in humans were 69.5% for
      AdHu5, 44% for AdHu26, 21% for AdC6 and 23.5% for AdC68. In addition, NAb titers
      to human Ad were consistently higher than those found to simian serotypes.
      Surprisingly, sera from some New-World monkey species were able to neutralize
      AdC6 and/or AdC68. A possible explanation for these findings and the implications
      for the development of Ad-vector vaccines are discussed in detail.

PMID- 20797753
TI  - Human papillomavirus type 16 E6 and E7 oncoproteins act synergistically to cause
      head and neck cancer in mice.
AB  - High-risk human papillomaviruses (HPVs) contribute to cervical and other
      anogenital cancers, and they are also linked etiologically to a subset of head
      and neck squamous cell carcinomas (HNSCC). We previously established a model for
      HPV-associated HNSCC in which we treated transgenic mice expressing the
      papillomaviral oncoproteins with the chemical carcinogen 4-nitroquinoline-1-oxide
      (4-NQO). We found that the HPV-16 E7 oncoprotein was highly potent in causing
      HNSCC, and its dominance masked any potential oncogenic contribution of E6, a
      second papillomaviral oncoprotein commonly expressed in human cancers. In the
      current study, we shortened the duration of treatment with 4-NQO to reduce the
      incidence of cancers and discovered a striking synergy between E6 and E7 in
      causing HNSCC. Comparing the oncogenic properties of wild-type versus mutant E6
      genes in this model for HNSCC uncovered a role for some but not other cellular
      targets of E6 previously shown to contribute to cervical cancer.

PMID- 20797755
TI  - Molecular determinants of HIV-1 subtype C coreceptor transition from R5 to R5X4.
AB  - The molecular mechanism(s) underlying transition from CCR5 to CXCR4 usage of
      subtype C viruses remain largely unknown. We previously identified a subtype C
      HIV-1 infected child whose virus demonstrated CXCR4 usage along with CCR5 upon
      longitudinal follow-up. Here we delineated the molecular determinants of Env
      involved in expanded coreceptor usage. Residue changes in three positions of Env
      V3 domain are critical for the dual tropic phenotype. These include: substitution
      of arginine at position 11, MG or LG insertion between positions 13 and 14, and
      substitution of threonine at the position immediately downstream of the GPGQ
      crown. Introducing these mutations into V3 region of a heterologous R5 virus also
      conferred dual tropism. Molecular modeling of V3 revealed a possible structural
      basis for the dual tropic phenotype. Determining what defines a subtype C X4
      virus will lead to a better understanding of subtype C HIV-1 pathogenesis, and
      will provide important information relevant to anti-retroviral therapy.

PMID- 20797756
TI  - IL-6-mediated intersubgenotypic variation of interferon sensitivity in hepatitis
      C virus genotype 2a/2b chimeric clones.
AB  - Mechanisms of difference in interferon sensitivity between hepatitis C virus
      (HCV) strains have yet to be clarified. Here, we constructed an infectious
      genotype2b clone and analyzed differences in interferon-alpha sensitivity between
      HCV-2b and 2a-JFH1 clones using intergenotypic homologous recombination. The HCV
      2b/JFH1 chimeric virus able to infect Huh7.5.1 cells and was significantly more
      sensitive to IFN than JFH1. IFN-induced expression of MxA and 25-OAS was
      significantly lower in JFH1 than in 2b/JFH1-infected cells. In JFH1-infected
      cells, expression of SOCS3 and its inducer, IL-6, was significantly higher than
      in 2b/JFH1-infected cells. The IFN-resistance of JFH1 cells was negated by siRNA
      knock down of SOCS3 expression and by pretreatment with anti-IL6 antibody. In
      conclusion, intergenotypic differences of IFN sensitivity of HCV may be
      attributable to the sequences of HCV structural proteins and can be determined by
      SOCS3 and IL-6 expression levels.

PMID- 20797757
TI  - Behavior, mass inventories and modeling evaluation of xenobiotic endocrine
      disrupting chemicals along an urban receiving wastewater river in Henan Province,
      China.
AB  - Historically, the locations of cities mainly depend on the available water source
      and the urban river not only supplies the fresh water to city but also receives
      its wastewaters. To analyze the influences of urban zone on its receiving water
      river, the Jialu River in Henan Province, China, a typical urban river was
      chosen. Water and sediment samples were collected along the river in 2007 to
      analyze the concentrations of xenobiotic endocrine-disrupting chemicals (XEDCs)
      including nonylphenol (NP), octylphenol (OP) and bisphenol A (BPA) in surface
      water and sediment. The results showed that the concentrations of OP, NP and BPA
      in surface water were 20.9-63.2 ng L(-1) (mean 39.8 ng L(-1)), 75.2-1520 ng L(-1)
      (mean 645 ng L(-1)), 410-2990 ng L(-1) (mean 1535 ng L(-1)), respectively. The
      lowest and highest concentrations of XEDCs in surface water were found in the
      upper stream and downstream of Zhengzhou urban zone, which was regarded as the
      major discharge source of these chemicals to this river. The concentrations of
      OP, NP and BPA in the sediment were 15.9-31.1 ng g(-1), 145-349 ng g(-1) and 626
      3584 ng g(-1) with the average concentrations of 21.4 ng g(-1), 257 ng g(-1) and
      2291 ng g(-1), respectively. The results of in situ sediment-water partition of
      XEDCs showed that the partition coefficients (log K(oc)') in the downstream were
      higher than that in the upstream, which was mainly caused by the retransfer of
      surface sediment from the upper stream to the downstream. Comparison of measured
      and theoretical inventories of XEDCs in sediment indicated that the residual time
      of XEDCs in sediment in the river was about 5 years, which was in the same order
      of magnitude with its big flood frequency. In order to predict concentration
      variances of XEDCs in surface water, a fugacity-hydrodynamic model was developed
      according to the concept of in series completely stirred tank reactors (CSTR).
      The model results showed that about 29-65% of XEDCs derived from the urban zone
      (about 2.0 t yr(-1)) would finally dissipate from aqueous phase in the 170 km
      downstream of the river. Assuming the discharge amount of XEDCs from the urban
      zone remaining constant, the predicted concentrations of the total XEDCs in the
      over 90% river reach would be higher than 1.0 MUg L(-1) under all normal, high
      water and low water season in 2007.

PMID- 20797758
TI  - Characterization of algal organic matter and formation of DBPs from
      chlor(am)ination.
AB  - The frequent occurrence of algal blooms in drinking water reservoirs causes
      problems to water supply, one of which is the release of algal organic matter in
      high concentrations to affect drinking water quality. Algal organic matter,
      including extracellular organic matter (EOM) and intracellular organic matter
      (IOM), was characterized. The formation of a variety of disinfection by-products
      (DBPs) in chlorination and chloramination of EOM, IOM and algal cells was
      evaluated. Natural organic matter (NOM) isolated from Suwannee River was also
      studied for comparison. EOM and IOM were rich in organic nitrogen, which
      consisted of high (over 10 kDa) and low (70-1000 Da) molecular weight (MW)
      organic matter, whilst the MW of organic carbon in EOM and IOM was relatively
      lower. IOM had a higher fraction of total organic nitrogen, with larger
      proportions of higher MW and more hydrophobic contents than did EOM. IOM also
      contained higher fractions of free amino acids but lower fractions of aliphatic
      amines than did EOM. During chlorination of EOM and IOM, organic chloramines were
      first formed and then became undetectable after 1 d. Chlorination of EOM and IOM
      produced more nitrogenous DBPs (N-DBPs) and haloaldehydes and less carbonaceous
      DBPs (C-DBPs) than did chlorination of NOM. Organic chloramines were found after
      3-d chloramination of EOM and IOM. The amounts of N-DBPs and C-DBPs formed from
      chloramination of EOM or IOM were much less than that from NOM. EOM produced less
      DBPs (except for trichloronitromethane) than did IOM and algal cells in
      chlorination and chloramination.

PMID- 20797759
TI  - The role of clay minerals in the reduction of nitrate in groundwater by zero
      valent iron.
AB  - Bench-scale batch experiments were performed to investigate the feasibility of
      using different types of clay minerals (bentonite, fuller's earth, and biotite)
      with zero-valent iron for their potential utility in enhancing nitrate reduction
      and ammonium control. Kinetics experiments performed with deionized water (DW)
      and groundwater (GW) revealed nitrate reduction by Fe(0) proceeded at
      significantly faster rate in GW than in DW, and such a difference was attributed
      to the formation of green rust in GW. The amendment of the minerals at the dose
      of 25 g L(-1) in Fe(0) reaction in GW resulted in approximately 41%, 43%, and 33%
      more removal of nitrate in 64 h reaction for bentonite, fuller's earth, and
      biotite, respectively, compared to Fe(0) alone reaction. The presumed role of the
      minerals in the rate enhancement was to provide sites for the formation of
      surface bound green rust. Bentonite and fuller's earth also effectively removed
      ammonium produced from nitrate reduction by adsorption, with the removal
      efficiencies significantly increased with the increase in mineral dose above 5:1
      Fe(0) to mineral mass ratio. Such a removal of ammonium was not observed for
      biotite, presumably due to its lack of swelling property. Equilibrium adsorption
      experiments indicated bentonite and fuller's earth had maximum ammonium
      adsorption capacity of 5.6 and 2.1 mg g(-1), respectively.

PMID- 20797760
TI  - Sorption of perfluorooctane sulfonate and perfluorooctanoate on activated sludge.
AB  - Perfluorinated compounds (PFCs) as one class of emerging pollutants have caused
      great attention in recent years. In this study, activated sludge was used to
      adsorb perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in aqueous
      solution in order to investigate their sorption behavior and possible uptake
      mechanism in wastewater treatment plants (WWTPs). Batch experiments including
      sorption kinetics, isotherm, and effect of solution pH and temperature were
      carried out. The sorption kinetics indicated that the equilibrium was reached
      within about 11h. The effect of pH and the zeta potential measurement implied
      that electrostatic repulsion prevented their sorption, but the protein
      composition on the heterogeneous surface of activated sludge was favorable for
      the sorption of PFOS and PFOA. The sorption isotherms of PFOS and PFOA as well as
      the comparative sorption of other PFCs with different CF chain length and
      different functional groups suggested that hydrophobic interaction also
      participated in the sorption process. Additionally, the active sorption on the
      living microorganism was also observed. The calculated distribution coefficient
      indicated that PFOS had a higher sorption tendency to activated sludge than PFOA.

PMID- 20797761
TI  - Sorption and desorption of carbamazepine from water by smectite clays.
AB  - Carbamazepine is a prescription anticonvulsant and mood stabilizing
      pharmaceutical administered to humans. Carbamazepine is persistent in the
      environment and frequently detected in water systems. In this study, sorption and
      desorption of carbamazepine from water was measured for smectite clays with the
      surface negative charges compensated with K+, Ca2+, NH4+, tetramethylammonium
      (TMA), trimethylphenylammonium (TMPA) and hexadecyltrimethylammonium (HDTMA)
      cations. The magnitude of sorption followed the order: TMPA-smectite>=HDTMA
      smectite>NH4-smectite>K-smectite>Ca-smectite?TMA-smectite. The greatest sorption
      of carbamazepine by TMPA-smectite is attributed to the interaction of conjugate
      aromatic moiety in carbamazepine with the phenyl ring in TMPA through pi-pi
      interaction. Partitioning process is the primary mechanism for carbamazepine
      uptake by HDTMA-smectite. For NH4-smectite the urea moiety in carbamazepine
      interacts with exchanged cation NH4+ by H-bonding hence demonstrating relatively
      higher adsorption. Sorption by K-, Ca- and TMA-smectites from water occurs on
      aluminosilicate mineral surfaces. These results implicate that carbamazepine
      sorption by soils occurs primarily in soil organic matter, and soil mineral
      fractions play a secondary role. Desorption of carbamazepine from the sorbents
      manifested an apparent hysteresis. Increasing irreversibility of desorption vs.
      sorption was observed for K-, Ca-, TMA-, TMPA- and HDTMA-clays as aqueous
      carbamazepine concentrations increased. Desorption hysteresis of carbamazepine
      from K-, Ca-, NH4-smectites was greater than that from TMPA- and HDTMA-clays,
      suggesting that the sequestrated carbamazepine molecules in smectite interlayers
      are more resistant to desorption compared to those sorbed by organic phases in
      smectite clays.

PMID- 20797762
TI  - Comparison of the effects of different salts on aerobic ammonia oxidizers for
      treating ammonium-rich organic wastewater by free and sodium alginate immobilized
      biomass system.
AB  - Partial nitrification to nitrite by aerobic ammonium oxidizing bacteria (AOB) is
      an important pre-treatment step for subsequent denitrification and anammox.
      Ammonium-rich wastewater may contain different amounts of organic matter and
      salts, which can influent the growth and activity of AOB significantly. In this
      study we investigated the influence of various salts on the performance of a
      partial nitrification process with free and sodium alginate immobilized biomass.
      Immobilization of the AOB cells did not have a great effect on the activity of
      the biomass, and complete inhibition for the immobilized AOB was observed at
      sulfate, chloride and phosphate concentrations of 500, 1000 and 700 mM,
      respectively. Free biomass was already inhibited at 300, 500 and 500 mM
      concentrations of sulfate, chloride and phosphate. Both free and immobilized
      biomass contained Nitrosomonas europaea/eutropha-like AOB. Compared to free
      nitrifying biomass, immobilized biomass appeared to be less sensitive to salt
      stress (maximum 30%). Since no difference in the composition of the AOB was
      observed between free and immobilized biomass, the protection by the
      immobilization is the most likely factor explaining the observed differences.

PMID- 20797763
TI  - QSAR-assisted design of an environmental catalyst for enhanced estrogen
      remediation.
AB  - A quantitative structure-activity relationship (QSAR) was used to streamline re
      design of a model environmental catalyst, horseradish peroxidase (HRP), for
      enhanced reactivity towards a target pollutant, steroid hormone 17beta-estradiol.
      This QSAR, embodying relationship between reaction rate and intermolecular
      binding distance, was used in silico to screen for mutations improving enzyme
      reactivity. Eight mutations mediating significant reductions in binding distances
      were expressed in Saccharomyces cerevisiae, and resulting recombinant HRP strains
      were analyzed to determine Michaelis-Menten parameters during reaction with the
      target substrate. Enzyme turnover rate, ln(kCAT), exhibited inverse relationship
      with model-predicted binding distances (R2=0.81), consistent with the QSAR.
      Additional analysis of native substrate degradation by selected mutants yielded
      unexpected increases in ln(kCAT) that were also inversely correlated (R2=1.00)
      with model-predicted binding distances. This suggests that the mechanism of
      improvement comprises a nonspecific "opening up" of the active site such that it
      better accommodates environmental estrogens of any size. The novel QSAR-assisted
      approach described herein offers specific advantages compared to conventional
      design strategies, most notably targeting an entire class of pollutants at one
      time and a flexible hybridization of benefits associated with rational design and
      directed evolution. Thus, this approach is a promising tool for improving enzyme
      mediated environmental remediation.

PMID- 20797764
TI  - Impact of humic substances on EROD activity in gill and liver of three-spined
      sticklebacks (Gasterosteus aculeatus).
AB  - Humic substances (HS) are ubiquitous in the environment and have been found to
      influence physiological functions of aquatic organisms. In the present study,
      three-spined sticklebacks (Gasterosteus aculeatus) were exposed to HS of
      different origins to evaluate effects on the 7-ethoxyresorufin O-deethylase
      (EROD) activity catalyzed by cytochrome P4501A (CYP1A) in the liver and the gill.
      To that end, three-spined sticklebacks were exposed for 48 h to different
      concentrations of synthetic humic acid (AHA), Nordic reservoir natural organic
      matter (N.R.-NOM) and water from six lakes with different concentrations of HS.
      EROD activity was significantly induced (3-6-fold) in the gills of fish exposed
      to water from all lakes except the lake with the lowest concentration of HS. All
      tested concentrations of AHA and N.R.-NOM significantly induced gill EROD
      activity and the induction was dose-dependent. AHA, but neither N.R.-NOM nor lake
      water, induced EROD activity in the liver. In addition, fish were exposed to the
      potent CYP1A inducers benzo(a)pyrene (BaP) and PCB126 in combination with AHA.
      Presence of AHA had no significant effect on EROD induction by BaP or PCB126. The
      components in HS responsible for EROD induction remain to be identified. Our
      finding that HS of both natural and synthetic origin induce EROD activity in the
      gill is of significance for the interpretation of biomonitoring data on EROD
      activity as well as for the choice of suitable reference waters.

PMID- 20797765
TI  - Age-dependent congener profiles of polychlorinated dibenzo-p-dioxins and
      dibenzofurans in the general population of Taiwan.
AB  - A congener profile of polychlorinated dibenzo-p-dioxin and dibenzofurans
      (PCDD/Fs) could provide valuable information for identifying possible sources of
      exposure to these compounds. The purpose of this study is to identify factors
      associated with PCDD/F congener profiles in the general population of Taiwan.
      Serum samples from 251 subjects of the general population in Taiwan were
      collected, and the levels of 17 2,3,7,8-chlorinated substituted PCDD/Fs were
      measured. The relationships between PCDD/F congener profiles and demographic
      parameters were evaluated using a multivariate analysis of variance method
      (MANOVA). Of the five demographic factors investigated, age was found to have the
      greatest impact on PCDD/F congener profiles. The PCDD/F congener pattern for the
      group I subjects (aged 18-29) was significantly different from those for the
      other three older age groups (p<0.001), and 12 congeners contributed to the
      effects (difference index: 71%). In addition, the group I subjects did not
      exhibit trends parallel to those of the other groups in the relationship between
      age and PCDD/F levels. Age was associated with PCDD/F levels and congener
      profiles in the general population of Taiwan and the young subjects (aged 18-29)
      was quite different from the other older subjects that could be influenced by the
      individual differences in pharmacokinetics and/or background exposure from
      dietary sources. We conclude that investigators must consider subjects' age and
      other underlying factors that could influence PCDD/F congener profiles in humans
      when identifying exposure sources.

PMID- 20797766
TI  - Validating a multi-biomarker approach with the shanny Lipophrys pholis to monitor
      oil spills in European marine ecosystems.
AB  - Oil spills are an importance source of polycyclic aromatic hydrocarbons (PAHs) in
      the aquatic environment. Intertidal communities are particularly sensitive since
      most organisms from these ecosystems are sessile or present reduced mobility.
      Hence, it is important to validate the use of resident species as sentinels to
      characterize the impact of oil spills on the rocky shores and the improvement
      during the restoration process. Recently the advantages of using the shanny
      Lipophrys pholis in pollution monitoring within the northwestern Atlantic coast
      has been pointed out. Therefore, with the aim of further validating the use of L.
      pholis in pollution monitoring associated with petrogenic hydrocarbon
      contamination, a multi-biomarker approach study was carried out 1 week after a
      moderate oil spill from the waste treatment plant (WTP) of the major Portuguese
      refinery in the north of Portugal (Petrogal). Fish collected at 2 km from the
      accident displayed a significant induction of ethoxyresorufin-O-deethylase
      activity (EROD) and fluorescent aromatic compounds (FACs) in bile (up to a 5-fold
      induction) in comparison with the pre-spill scenario, and a 15% induction in
      erythrocytic nuclear abnormalities (ENA), a biomarker of genotoxicity. In
      contrast, no significant differences were recorded in the reference site. In
      order to better characterize the time-course accumulation of FACs in bile after a
      PAH insult, laboratory exposure of L. pholis to benzo[a]pyrene (B[a]P) was
      performed. A clear dose-response accumulation of B[a]P metabolites was observed
      that closely reflected nominal exposure concentrations already after 3d. Overall,
      the findings of the present study highlight the potential of L. pholis in
      pollution monitoring dealing not only with chronic contamination, but also with
      oil spill accidents of a moderate scale. Taking into consideration that EROD and
      FACs determinations in L. pholis are cost effective, rapid and easy to use, they
      offer a great potential to be incorporated into risk assessment of PAHs in the
      scope of national monitoring programs and the European Water Policy legislation.

PMID- 20797767
TI  - Defining the surface adsorption and internalization of copper and cadmium in a
      soil bacterium, Pseudomonas putida.
AB  - The distribution of cadmium (Cd) and copper (Cu) ions onto and within two soil
      pseudomonads, Pseudomonas putida strains KT2440 and Corvallis, was investigated
      using selective extraction procedures and modeled using Langmuir isotherms.
      Cadmium and Cu associated differently with the surface, periplasm and cytoplasm
      of the two strains. Both of these pseudomonad cells allowed more Cu to pass into
      the periplasmic space and to the cytoplasm than Cd. The distribution of Cu among
      the cellular spaces was solution concentration dependent, with limited amounts of
      Cu entering the cell at higher exposure concentrations. The Langmuir isotherm
      with a single binding site fit well to the observed data for Cu cell association.
      Cadmium was mainly found on the surface of the cells. The capacity of surface
      exchange sites for Cd increased with solution concentration, possibly indicating
      a modification of surface functional groups with ion concentration. This surface
      sorption behavior of Cd was best described using a two-site Langmuir model,
      whereas all other Cu and Cd associations were described using a one-site model.
      Although potentiometric titration identified differences in site densities for
      proton binding to the two strains, these differences were not consistently
      displayed with Cu and Cd surface interactions.

PMID- 20797768
TI  - Further potentials in the joint implementation of life cycle assessment and data
      envelopment analysis.
AB  - The combined application of Life Cycle Assessment and Data Envelopment Analysis
      has been recently proposed to provide a tool for the comprehensive assessment of
      the environmental and operational performance of multiple similar entities. Among
      the acknowledged advantages of LCA+DEA methodology, eco-efficiency verification
      and avoidance of average inventories are usually highlighted. However, given the
      novelty of LCA+DEA methods, a high number of additional potentials remain
      unexplored. In this sense, there are some features that are worth detailing given
      their wide interest to enhance LCA performance. Emphasis is laid on the improved
      interpretation of LCA results through the complementary use of DEA with respect
      to: (i) super-efficiency analysis to facilitate the selection of reference
      performers, (ii) inter- and intra-assessments of multiple data sets within any
      specific sector with benchmarking and trend analysis purposes, (iii) integration
      of an economic dimension in order to enrich sustainability assessments, and (iv)
      window analysis to evaluate environmental impact efficiency over a certain period
      of time. Furthermore, the capability of LCA+DEA methodology to be generally
      implemented in a wide range of scenarios is discussed. These further potentials
      are explained and demonstrated via the presentation of brief case studies based
      on real data sets.

PMID- 20797769
TI  - Temporal variation of nitro-polycyclic aromatic hydrocarbons in PM10 and PM2.5
      collected in Northern Mexico City.
AB  - With the aim to determine the presence of individual nitro-PAH contained in
      particles in the atmosphere of Mexico City, a monitoring campaign for particulate
      matter (PM(10) and PM(2.5)) was carried out in Northern Mexico City, from April
      2006 to February 2007. The PM(10) annual median concentration was 65.2MUgm(-3)
      associated to 7.6MUgm(-3) of solvent-extractable organic matter (SEOM)
      corresponding to 11.4% of the PM(10) concentration and 38.6MUgm(-3) with 5.9MUgm(
      3) SEOM corresponding to 15.2% for PM(2.5). PM concentration and SEOM varied with
      the season and the particle size. The quantification of nitro-polycyclic aromatic
      hydrocarbons (nitro-PAH) was developed through the standards addition method
      under two schemes: reference standard with and without matrix, the former giving
      the best results. The recovery percentages varied with the extraction method
      within the 52 to 97% range depending on each nitro-PAH. The determination of the
      latter was effected with and without sample purification, also termed
      fractioning, giving similar results. 8 nitro-PAH were quantified, and their sum
      ranged from 111 to 819pgm(-3) for PM(10) and from 58 to 383pgm(-3) for PM(2.5),
      depending on the season. The greatest concentration was for 9-Nitroanthracene in
      PM(10) and PM(2.5), detected during the cold-dry season, with a median (10th-90th
      percentiles) concentration in 235pgm(-3) (66-449pgm(-3)) for PM(10) and 73pgm(-3)
      (18-117pgm(-3)) for PM(2.5). The correlation among mass concentrations of the
      nitro-PAH and criteria pollutants was statistically significant for some nitro
      PAH with PM(10), SEOM in PM(10), SEOM in PM(2.5), NO(X), NO(2) and CO, suggesting
      either sources, primary or secondary origin. The measured concentrations of nitro
      PAH were higher than those reported in other countries, but lower than those from
      Chinese cities. Knowledge of nitro-PAH atmospheric concentrations can aid during
      the surveillance of diseases (cardiovascular and cancer risk) associated with
      these exposures.

PMID- 20797770
TI  - Feasibility of using 236U to reconstruct close-in fallout deposition from the
      Hiroshima atomic bomb.
AB  - The first results on the feasibility of using (236)U to reconstruct the level and
      spatial distribution of close-in fallout deposition from the Hiroshima A-bomb are
      reported, coupled with the use of global fallout (137)Cs and (239+240)Pu. The
      results for global fallout (236)U in soil samples (0-30cm) from Ishikawa
      prefecture showed that the deposition density of (236)U from the global fallout
      can be accurately evaluated using AMS. All deposited (236)U, (137)Cs and
      (239+240)Pu appeared to have been recovered using 30-cm cores. It was also noted
      from the depth profiles for (236)U/(239+240)Pu and (236)U/(137)Cs ratios that the
      downward behavior of (236)U in the soil was apparently similar to that of
      (239+240)Pu, while the (137)Cs was liable to be retained in upper layers compared
      with (236)U and (239+240)Pu. The accumulated levels were 1.78*10(13)atomsm(-2)
      for (236)U, 4340Bqm(-2) for (137)Cs and 141Bqm(-2) for (239+240)Pu. The ratios of
      (236)U/(137)Cs and (236)U/(239+240)Pu were (4.10+/-0.12)*10(9) and (1.26+/
      0.04)*10(11)atomsBq(-1), respectively. Results of (236)U, (137)Cs and (239+240)Pu
      measurements for the seven soil cores (0-30cm) from Hiroshima were discussed on
      the basis of ratios of (236)U/(137)Cs and (236)U/(239+240)Pu by comparing with
      those from the background area in Ishikawa, indicating that the global fallout
      dominates the current level of (236)U accumulation in soil in the Black-rain area
      around Hiroshima after the Hiroshima bomb, and the contribution of the close-in
      fallout (236)U produced by the Hiroshima A-bomb seems difficult to observe.

PMID- 20797771
TI  - Mercury in parasitic nematodes and trematodes and their double-crested cormorant
      hosts: bioaccumulation in the face of sequestration by nematodes.
AB  - Endoparasites can alter their host's heavy metal concentrations by sequestering
      metals in their own tissues. Contracaecum spp. (a nematode), but not
      Drepanocephalus spathans (a trematode), were bioaccumulating mercury to
      concentrations 1.5 times above cormorant hosts. Nematodes did not have
      significantly greater stable nitrogen isotope values (delta(15)N) than their
      hosts, which is contradictory to prey-predator trophic enrichment studies, but is
      in agreement with other endoparasite-host relationships. However, Contracaecum
      spp. delta(13)C values were significantly greater than their hosts, which suggest
      that nematodes were consuming host tissues. Nematodes were accumulating and thus
      sequestering some of their cormorant hosts' body burden of methyl mercury;
      however, they were not dramatically reducing their hosts' accumulation of methyl
      mercury.

PMID- 20797772
TI  - Trust-based environmental regulation.
AB  - Within this paper, we examine the contribution that trust-based relationships can
      make to achieving better-and particularly more effective, efficient and equitable
      environmental regulation. While levels of trust in regulators, regulatory
      processes and outcomes are often discussed, the influence of trust on different
      actors and on different measures of regulatory performance is poorly understood.
      Within this paper, we define trust-based environmental regulation as a specific
      regulatory style that involves openness and cooperation in interaction between
      regulated, regulators and third-party stakeholders in order to achieve
      environmental protection objectives. We then discuss the pros and cons of trust
      relationships between regulators, regulated businesses and citizens for achieving
      behavioural change towards greater environmental protection. To illustrate the
      significance of these issues, we then examine three forms of contractual
      regulatory style where trust relationships are critically important: responsive
      regulation, self-regulation and environmental agreements. Based on this analysis,
      we highlight the importance of trust-based relationships, and we argue that one
      of the greatest contributions of trust-based environmental regulation is to
      challenge how we think about regulation. Trust is often understood as enabling
      existing regulatory relationships or in the case of self-regulation as a
      complement to regulation. However, we argue that the real potential of trust is
      to open up new ways for participants in regulatory regimes to engage in
      collective action, to go beyond a perception of regulation as driven by the
      competing interests of individual actors, and thus, to open up new channels of
      influence for behavioural change towards greater environmental protection. Our
      analysis therefore has great relevance for future research and for on-going
      debates on the future of regulation.

PMID- 20797773
TI  - Long-term human exposure to lead from different media and intake pathways.
AB  - Lead (Pb) is well known as an environmental pollutant: it can accumulate in
      various media, so actual lead exposure reflects both historical and present
      contaminations. Two main challenges then emerge: obtaining updated information to
      gain an overall picture of the sources of exposure, and predicting the resulting
      internal body exposure levels and effects that occur under long-term exposure
      conditions. In this paper, a modeling approach is used to meet these challenges
      with reference to Danish exposure conditions. Levels of lead content in various
      media have been coupled with data for lead intake and absorption in the human
      body, for both children and adults. An age-dependent biokinetic model allows then
      for determination of the blood lead levels resulting from chronic exposure. The
      study shows that the actual intake of lead is up to 27% of the Provisional
      Tolerable Daily Intake (PTDI) for children and around 8% for adults. It is
      confirmed that the critical route of exposure is via ingestion, accounting for
      99% of total lead intake, while inhalation contributes only to 1% of total lead
      intake. The resulting lead levels in the blood after 2 years of exposure to
      actual contamination conditions have been estimated as up to 2.2MUg/dl in
      children and almost 1MUg/dl in adults. Impacts from lead can occur even at such
      levels. The role of historical and present sources to lead in the environment is
      discussed, and, for specific child and adult exposure scenarios, external
      internal concentration relationships for the direct linkage between lead in
      environmental media and resulting concentrations of lead in blood are then
      presented.

PMID- 20797774
TI  - Short versus extended thromboprophylaxis after total knee arthroplasty: a
      randomized comparison.
AB  - INTRODUCTION: The optimal duration of thromboprophylaxis after total knee
      arthroplasty remains uncertain. MATERIAL AND METHODS: We performed a randomized,
      open trial to determine whether to stop thromboprophylactic therapy at Day 10+/-2
      ('short thromboprophylaxis') was non-inferior to continue thromboprophylactic
      therapy up to Day 35+/-5 ('extended thromboprophylaxis') after total knee
      arthroplasty. At Day 7+/-2, subjects were screened by ultrasonography for
      asymptomatic deep-vein thrombosis and randomized. The primary outcome was a
      composite of proximal deep-vein thrombosis, any symptomatic deep-vein thrombosis,
      non-fatal symptomatic pulmonary embolism, major bleeding, heparin-induced
      thrombocytopenia, or all-cause death up to Day 35+/-5. The secondary outcome was
      ultrasonographic (extension or new onset) distal deep-vein thrombosis at Day 35+/
      5. RESULTS: Twenty-one patients (2.4%) were not randomized, because of
      asymptomatic proximal deep-vein thrombosis on systematic ultrasonography at Day
      7+/-2. Among the 857 randomized patients, mean (SD) duration of anticoagulant
      treatment was 11.2 (6.7) and 33.9 (3.7) days in the short and extended
      thromboprophylaxis groups, respectively. The respective rates of the primary
      outcome were 4.0% (17/420) and 2.4% (10/422), with an absolute difference of 1.7%
      (90% confidence interval, -0.3 to 3.7). In 285 patients with asymptomatic distal
      deep-vein thrombosis at Day 7+/-2, the respective rates of the primary outcome
      were 7.8% and 2.8% (p=0.067). The rates of the secondary outcome were 14.8%
      (62/420) and 4.5% (19/422), respectively (p<0.001). CONCLUSIONS: Short
      thromboprophylaxis was not non-inferior to extended thromboprophylaxis after
      total knee arthroplasty. In this setting, the thromboembolic risk persisted
      longer than seven days, notably in patients with asymptomatic distal deep-vein
      thrombosis at discharge. ClinicalTrials.gov number: NCT00362492.

PMID- 20797775
TI  - The role of restaging borderline ovarian tumors: single institution experience
      and review of the literature.
AB  - BACKGROUND: Borderline ovarian tumors (BOTs) are a histological category of
      epithelial ovarian tumors and 70% of them are early diagnosed (stage I). Since
      early stage is the most important prognostic factor, restaging procedure could be
      justified. This study aims to evaluate the role of restaging surgery in the
      management of patients with borderline ovarian tumors referred to our Institution
      after being incompletely surgically staged in other hospitals. MATERIALS AND
      METHODS: We retrospectively reviewed the charts of patients with BOT who were
      referred to our centre to undergo restaging procedure. From December 1995 to May
      2008, 186 patients were treated for BOT and 70 patients met the inclusion
      criteria. Data collected included patients' age, primary and re-staging surgery
      details, FIGO stage after first and second procedure, pathological findings, and
      follow-up data. RESULTS: FIGO stage after primary surgery was IA in 46 patients
      (68.6%), IB in 7 patients (10.4%), IC in 12 patients (17.9%, 6 due to ruptured
      cyst), IIA in 1 patient (1.4%), IIB in 1 patient (1.4%), III B in 2 patients
      (2.8%), and IIIC in 1 patient (1.4%). Among stage I patients (representing 97% of
      all patients), 12.3% (8 patients) were up-staged. The upstaging rate among serous
      tumors was 16.2%, and 4% among mucinous tumors. The mean follow-up time was 60.4
      months from restaging surgery (SD 30.6 months). We observed 8 primary recurrences
      of the disease and 3 second recurrences. CONCLUSIONS: There were no differences
      in terms of overall survival between patients who were upstaged and those who
      were not. Restaging procedure does not seem to have a significant impact on the
      management of patients diagnosed with borderline ovarian tumors, especially in
      mucinous subtype and apparent FIGO stage higher than I.

PMID- 20797776
TI  - A critical re-appraisal of BRCA1 methylation studies in ovarian cancer.
AB  - A central challenge facing gynecologic oncology is achieving personalized care in
      ovarian cancer treatment. The current ovarian cancer classification scheme
      distinguishes tumors based on histopathologic subtype, grade, and surgical stage.
      Recent molecular investigations have highlighted distinguishing genetic features
      of certain tumors within a given category, and given the rapid pace of
      technologic advancement combined with plummeting costs for complete genomic
      sequencing this classification will markedly improve. Clinical studies have begun
      to explore the influence of currently known distinctions on the natural history
      of the disease, most recently with particular attention to the BRCA1 status of
      tumors. Mutations in the BRCA1 gene have long been known to increase a woman's
      risk of developing ovarian cancer. As has been shown, BRCA1-associated ovarian
      cancers may be associated with characteristic differences in therapeutic response
      and overall survival, and further defining these subsets may become instrumental
      in clinical decision-making. Therefore, given the eightfold difference (5-40%) in
      reported frequency of BRCA1 inactivation by methylation in the pioneering studies
      in the field, a critical re-appraisal of the literature, techniques, samples
      used, and interpretations of BRCA1 inactivation is warranted along with a review
      of the more recent and comprehensive molecular studies.

PMID- 20797777
TI  - CA125 nadir concentration is an independent predictor of tumor recurrence in
      patients with ovarian cancer: a population-based study.
AB  - OBJECTIVE: Previous reports described the prognostic value of the serum CA125
      level after primary treatment (CA125 nadir) in a selection of ovarian cancer
      patients. Our primary objective was to determine whether the CA125 nadir level is
      of prognostic value on the progression-free survival (PFS) and on overall
      survival (OS) in epithelial ovarian cancer (EOC) patients in all stages of
      disease who reached complete remission (CR). METHODS: Patients were selected from
      a population-based study on EOC patients diagnosed between 1996 and 2006 in 11
      Dutch hospitals. All 331 patients who reached CR (i.e. no physical or
      radiological signs of residual disease and CA125 values <=35 kU/L) after primary
      treatment were included. The Kaplan-Meier survival curves of PFS and OS in CA125
      nadir <=5 kU/L and >5 kU/L were compared using the log-rank test. Multivariate
      Cox regression analyses were performed to study the factors that independently
      influence survival. RESULTS: A CA125 nadir <=5 kU/L (n=69) was significantly
      associated with both a longer PFS and longer OS (log-rank test P<0.01 and P=0.03,
      respectively). The CA125 nadir was an independent prognostic variable (HR=1.51,
      95% CI: 1.04-2.31) for PFS next to histological type, FIGO stage and residual
      tumor after surgery. CONCLUSIONS: EOC patients who were in CR after standard
      primary treatment and attained CA125 nadir values of <=5 kU/L had a significantly
      longer PFS and OS. Moreover, the CA125 nadir of <=5 kU/L is an independent
      predictor of tumor recurrence.

PMID- 20797778
TI  - VEGF polymorphisms in early cervical cancer susceptibility, angiogenesis, and
      survival.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) plays an important role in
      cervical carcinogenesis. We hypothesized that VEGF genetic polymorphisms may
      affect cancer susceptibility, angiogenesis, and survival in patients with early
      cervical cancer. METHODS: Among 215 healthy subjects and 199 early cervical
      cancer patients who were treated with surgical resection, we specifically
      investigated four genetic polymorphisms within the VEGF gene (-2578C>A, -460 T>C,
      +405G>C, and +936C>T). VEGF and CD31 microvessel density (MVD) were measured
      using tissue microarrays constructed from 117 patients who had available tissue.
      RESULTS: Risk of cervical cancer was decreased in subjects with the VEGF -2578A/A
      genotype (adjusted OR=0.39, 95% CI 0.16-0.96). Angiogenesis measured by CD31 MVD
      was significantly decreased in patients with the VEGF +405C/C genotype and VEGF 
      2578C - -460 T - +405C haplotype (recessive model; adjusted OR=0.32, 95% CI 0.11
      0.99, equally). Moreover, VEGF +405C/C and VEGF -2578C - -460 T - +405C haplotype
      were significantly related to shorter disease-free survival (adjusted HR=3.18,
      95% CI 1.13-8.94, equally) and overall survival (adjusted HR=8.86, 95% CI 1.40
      56.08, equally) by multiple Cox regression analysis. CONCLUSION: Polymorphisms of
      VEGF genes may affect cancer susceptibility and survival of early cervical cancer
      by modulating tumor angiogenesis. Prospective study among homogeneously treated
      patients is warranted.

PMID- 20797780
TI  - Health and philanthropy--the tobacco connection.

PMID- 20797781
TI  - Human macrophage activation triggered by chitotriosidase-mediated chitin and
      chitosan degradation.
AB  - Chitin a biopolymer composed of N-acetyl-D-glucosamine (GlcNAc) residues is a
      structural component in human pathogens such as nematodes and fungi.
      Deacetylation of chitin generates chitosan which has been recently found in the
      cell wall of Cryptococcus neoformans a human pathogenic fungi causing life
      threatening meningoencephalitis. While chitin and chitosan are currently studied
      as compounds of medical devices such as wound dressings or nanoparticles, its
      immunostimulatory potential and its metabolic fate in humans remains unclear. To
      gain more fundamental insights on the immunological properties of chitin and
      chitosan in humans we studied their degradation by chitotriosidase (ChT) and
      their inflammatory properties on human macrophages. Our data show that
      chitinhexamer is not able to increase the expression of inflammatory cytokines
      significantly. However, we measured an induction of ChT secretion upon
      chitinhexamer treatment. By analysis of human ChT-mediated cleavage of chitosan
      we could demonstrate a special mechanism of substrate cleavage, defined as
      processivity. Processivity enables the rapid production of small and diffusible
      chitin and chitosan fragments. In comparison to large chitosan polymers these ChT
      produced small chitin/chitosan oligomers exhibit strongest macrophage activating
      properties reflected by an enhanced ChT secretion. Here we show that recognition
      of chitin and chitosan by human macrophages is triggered by the enzyme ChT due to
      the production of chitin and chitosan oligomers which in turn stimulates further
      ChT secretion and consequently oligomers production. Finally, we demonstrate that
      despite the high cooperativity of chitosan and chitin clearance by ChT seems very
      specific as no inflammatory response could be detected.

PMID- 20797779
TI  - A C-type lectin collaborates with a CD45 phosphatase homolog to facilitate West
      Nile virus infection of mosquitoes.
AB  - West Nile virus (WNV) is the most common arthropod-borne flavivirus in the United
      States; however, the vector ligand(s) that participate in infection are not
      known. We now show that an Aedes aegypti C-type lectin, mosGCTL-1, is induced by
      WNV, interacts with WNV in a calcium-dependent manner, and facilitates infection
      in vivo and in vitro. A mosquito homolog of human CD45 in A. aegypti, designated
      mosPTP-1, recruits mosGCTL-1 to enable viral attachment to cells and to enhance
      viral entry. In vivo experiments show that mosGCTL-1 and mosPTP-1 function as
      part of the same pathway and are critical for WNV infection of mosquitoes. A
      similar phenomenon was also observed in Culex quinquefasciatus, a natural vector
      of WNV, further demonstrating that these genes participate in WNV infection.
      During the mosquito blood-feeding process, WNV infection was blocked in vivo with
      mosGCTL-1 antibodies. A molecular understanding of flaviviral-arthropod
      interactions may lead to strategies to control viral dissemination in nature.

PMID- 20797782
TI  - Surface modification of PLGA nanospheres with Gd-DTPA and Gd-DOTA for high
      relaxivity MRI contrast agents.
AB  - The preparation of particulate contrast agents for magnetic resonance imaging
      (MRI) based on biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanocarriers
      is reported. By spacer-aided covalent surface-grafting of the prominent chelating
      ligands diethylenetriaminepentaacetic acid (DTPA) and 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), respectively, up to 236
      MUg gadolinium per mg PLGA can be immobilized in a stable manner. Due to the
      localisation at the particle surface, water protons may effectively interact with
      the gadolinium chelates and the modified particles exhibit high proton
      relaxivities as confirmed by T1 relaxivities of up to 17.5 mm(-1)s(-1) (25 
      degrees C, 1.41 T) in case of Gd-DOTA-functionalized carriers and also supported
      by NMRD profiles. The obtained values compare favorably with marketed low
      molecular weight contrast agents and thus suggest suitability for in vivo use.

PMID- 20797783
TI  - The effect of nanofiber-guided cell alignment on the preferential differentiation
      of neural stem cells.
AB  - Stem cells display sensitivity to substrate presentation of topographical cues
      via changes in cell morphology. These biomechanical responses may be transmitted
      to the nucleus through cytoskeletal-linked signaling pathways. Here we
      investigate the influence of aligned substratum topography on the cell morphology
      and subsequently, the neuronal differentiation capabilities of adult neural stem
      cells (ANSCs). ANSCs that were cultured on aligned fibers elongated along the
      major fiber axis. Upon induction of differentiation with retinoic acid, a higher
      fraction of cells on aligned fibers exhibited markers of neuronal differentiation
      as compared with cells on random fiber or unpatterned surfaces. This effect was
      in part due to substrate selectivity, whereby aligned fiber substrates were less
      receptive to the attachment and continued survival of oligodendrocytes than
      random fiber or unpatterned substrates. Substrate-induced elongation alone was
      also effective in upregulating canonical Wnt signaling in ANSCs, which was
      further potentiated by retinoic acid treatment. These findings suggest a
      mechanism by which morphological control of stem cells operates in concert with
      biochemical cues for cell fate determination.

PMID- 20797785
TI  - Regulation of early trophoblast differentiation - lessons from the mouse.
AB  - The earliest stages of trophoblast differentiation are of tremendous importance
      to mediate implantation and to lay the anatomical foundations for normal
      placental development and function throughout gestation. Yet our molecular
      insights into these early developmental processes in humans have been limited by
      the inaccessibility of material and the unavailability of trophoblast cell lines
      that fully recapitulate the behaviour of early placental trophoblast. In this
      review we highlight recent advances that have come from the study of distinct
      stem cell types representative of the embryonic and extraembryonic lineages in
      the mouse, and from the study of mouse mutants. These models have revealed the
      presence of intricate transcriptional networks that are set up by signalling
      pathways, translating extracellular growth factor and cell positional information
      into distinct lineage-specific transcriptional programmes. The trophoblast
      specificity of these networks is ensured by epigenetic mechanisms including DNA
      methylation and histone modifications that complement each other to define
      trophoblast cell fate and differentiation. Despite the anatomical differences
      between mouse and human placentas, it seems that important aspects of early
      trophoblast specification are conserved between both species. Thus we may be able
      to build on our insights from the mouse to better understand early trophoblast
      differentiation in the human conceptus which is important for improving assisted
      reproductive technologies and may enable us in the future to derive human
      trophoblast stem cell lines. These advances will facilitate the investigation of
      genetic, epigenetic and environmental influences on early trophoblast
      differentiation in normal as well as in pathological conditions.

PMID- 20797784
TI  - Bioactive polymer/extracellular matrix scaffolds fabricated with a flow perfusion
      bioreactor for cartilage tissue engineering.
AB  - In this study, electrospun poly(E-caprolactone) (PCL) microfiber scaffolds,
      coated with cartilaginous extracellular matrix (ECM), were fabricated by first
      culturing chondrocytes under dynamic conditions in a flow perfusion bioreactor
      and then decellularizing the cellular constructs. The decellularization procedure
      yielded acellular PCL/ECM composite scaffolds containing glycosaminoglycan and
      collagen. PCL/ECM composite scaffolds were evaluated for their ability to support
      the chondrogenic differentiation of mesenchymal stem cells (MSCs) in vitro using
      serum-free medium with or without the addition of transforming growth factor
      beta1 (TGF-beta1). PCL/ECM composite scaffolds supported chondrogenic
      differentiation induced by TGF-beta1 exposure, as evidenced in the up-regulation
      of aggrecan (11.6 +/- 3.8 fold) and collagen type II (668.4 +/- 317.7 fold) gene
      expression. The presence of cartilaginous matrix alone reduced collagen type I
      gene expression to levels observed with TGF-beta1 treatment. Cartilaginous matrix
      further enhanced the effects of growth factor treatment on MSC chondrogenesis as
      evidenced in the higher glycosaminoglycan synthetic activity for cells cultured
      on PCL/ECM composite scaffolds. Therefore, flow perfusion culture of chondrocytes
      on electrospun microfiber scaffolds is a promising method to fabricate
      polymer/extracellular matrix composite scaffolds that incorporate both natural
      and synthetic components to provide biological signals for cartilage tissue
      engineering applications.

PMID- 20797786
TI  - Responses of Cynara cardunculus L. to single and combined cadmium and nickel
      treatment conditions.
AB  - A greenhouse pot experiment was carried out to study the responses of Cynara
      cardunculus L. (cardoon) to cadmium and nickel. Three groups of 12 pots each were
      planted with cardoon plants and spiked with single and combined cadmium and
      nickel aqueous solutions. The bioavailable metal concentrations, measured in
      soil, ranged widely and were up to 246.7 mg kg-1 for Cd and 61.1 mg kg-1 for Ni.
      Under Cd treatment, cardoon growth remained unaffected, while increased Ni soil
      concentrations inhibited plant growth and were lethal to the highly treated
      plants. In the combined Cd and Ni treatments, an antagonistic effect was observed
      between the two metals. Cadmium and nickel concentrations in cardoon tissues rose
      with increasing metal concentrations in the soil. Cadmium and nickel contents in
      shoots reached 169.3 and 342.3 mg kg-1 in the single treatments while, under the
      combined Cd and Ni treatments, they were up to 235.0 and 440.7 mg kg-1,
      respectively. Generally, mean contents of both metals in the shoots were higher
      than in the roots and the translocation factor was greater than 1. A possible
      enhancing effect of nickel on cadmium uptake was observed. Cardoon showed
      characteristics of a Cd accumulator.

PMID- 20797787
TI  - Morphometry of the epidermis of an invasive megascoelecid earthworm (Amynthas
      gracilis, Kinberg 1867) inhabiting actively volcanic soils in the Azores
      archipelago.
AB  - For the first time, the structure, dimensions, and composition of the epidermis
      of an invasive earthworm species that has successfully colonized hostile
      conditions in actively volcanic soil on Sao Miguel (Azores) have been measured.
      Metal concentrations in actively volcanic (Furnas) and volcanically inactive
      (Faja) soils were similar; however, Furnas soil was characterised by elevated
      temperature (10 degrees C differential), relative hypoxia, extremely high CO(2)
      tension, and accompanying acidity. The epidermis of earthworm's resident at Faja
      was approximately twice the thickness of the epidermis of conspecifics resident
      in Furnas soil. Reference worms transferred to Furnas soil for 14 days
      experienced an epidermal thinning of approximately 51%. In comparison, when
      Furnas earthworms were transferred to mesocosms at the relatively benign Faja
      site, their epidermal thickness increased by approximately 21% over 14 days.
      Earthworms resident in Furnas soil had higher goblet cell counts than the
      residents of volcanically inactive soil on a neighbouring island (S. Maria).
      Transferring worms from S. Maria to mesocosms at Furnas induced a significant
      increase in goblet cell counts. Clearly, the active volcanic environment at
      Furnas poses a multifactorial stress challenge to the epigeic A. gracilis
      colonizer.

PMID- 20797788
TI  - Biochemical, physiological and behavioural markers in the endobenthic bivalve
      Scrobicularia plana as tools for the assessment of estuarine sediment quality.
AB  - The aim of this study was to link the responses at different levels of biological
      organisation of the endobenthic bivalve Scrobicularia plana differentially
      exposed to anthropogenic pressure. Clams were collected in April 2008 from three
      estuaries along a pollution gradient (Goyen < Loire < Seine). Biomarkers of
      defence (metallothionein concentration and glutathione-S-transferase activity)
      were activated in the Loire and the Seine. Biomarkers of damage revealed
      neurotoxicity (decreased AChE activity) and impairment of digestive enzyme
      activities (cellulase or amylase) in these estuaries. The highest lactate
      dehydrogenase activity was registered in the Loire estuary, in parallel with
      enhanced levels of vanadium (a metal present in petroleum), likely as a
      consequence of a small oil spill that occurred one month before the sampling
      collection. Physiological biomarkers (energy reserves as glycogen, lipids and
      proteins, condition and gonado-somatic indices) showed a few intersite
      differences. However, the median size was significantly lower in clams exposed to
      direct (chemicals) or indirect (available food) effects in the most contaminated
      site. Burrowing behaviour was disturbed in clams from both of the Loire and Seine
      estuaries, a response probably due to physiological impairment rather than to
      avoidance of contaminated sediment. The activation of defence mechanisms towards
      metals (metallothionein) and other classes of contaminants (the biotransformation
      enzyme glutathione-S-transferase) do not ensure a total protection since a number
      of impairments were observed at the infra-organismal (AChE and digestive enzyme
      activities) and individual (burrowing behaviour) levels in relation to the degree
      of anthropogenic pressure. However, even in the most contaminated estuary
      (Seine), historical records do not show a consistent decrease of S. plana
      populations.

PMID- 20797789
TI  - Evaluation of 2,4-D and Dicamba genotoxicity in bean seedlings using comet and
      RAPD assays.
AB  - The present study was undertaken to evaluate genotoxic potential of two auxinic
      herbicides [2,4-dicholorophenoxy acetic acid (2,4-D) and 3,6-dichloro-2
      methoxybenzoic acid (Dicamba)] in the roots of common bean (Phaseolus vulgaris
      L.) seedlings. Two-day-old etiolated seedlings were treated with 10 ppm methyl
      methanesulfonate (MMS, positive control) or 0.1, 0.2, or 0.3 ppm of either 2,4-D
      or Dicamba. At the end of a 96 h growth period, root growth, total soluble
      protein content, DNA damage in individual cells (comet assay scores) and randomly
      amplified polymorphic DNA (RAPD) profiles were used as endpoints of genotoxicity.
      2,4-D and Dicamba were clearly dose-dependent root growth inhibitors. Total
      soluble protein content was significantly decreased in the positive control and
      at high concentrations (0.2 and 0.3 ppm) of Dicamba. Soluble protein content
      increased significantly only at 0.3 ppm 2,4-D (P<0.05). In the comet assay, DNA
      fragmentation increased in a dose-dependent manner. The diagnostic and phenetic
      analyzes of appeared and/or disappeared RAPD bands indicated that dose-dependent
      DNA polymorphism was induced by both herbicides. Genomic template stability was
      significantly affected at all 2,4-D and Dicamba doses tested. Overall 2,4-D and
      Dicamba have similar effects on DNA damage detected by comet and RAPD assays.

PMID- 20797790
TI  - Mental health courts and diversion programs: A global survey.
AB  - Research techniques in the fields of mental health courts and diversion need to
      be improved. As well, insights are provided as to how the evaluations of these
      programs could be strengthened. There are reports from jurisdictions managing
      mentally disordered accused in the criminal justice system without the benefit of
      these programs. A distillation of the commonalities from those jurisdictions
      suggests that providing the police with better options at first instance (pre
      arrest diversion), broader discretion on the part of the prosecutor (pre-plea
      diversion), and greater jurisdiction on the part of the courts (to impose
      treatment and monitoring) may have provided those jurisdictions with an
      adequately functioning system which, as of yet, has not created a need for mental
      health courts and formal diversion programs. Recommendations are made for future
      directions.

PMID- 20797792
TI  - The fight between the teleost fish immune response and aquatic viruses.
AB  - Teleost fish represent a transition point on the phylogenetic spectrum between
      invertebrates that depend only on innate immunity and mammals that heavily depend
      on adaptive immunity. The major mechanisms of the teleost fish innate immune
      response are suggested to be similar to mammals, although fine details of the
      process require further studies. Within the innate immune response the type I
      interferon (IFN) system is an essential innate antiviral component that protects
      fish from some virus infections. The current progress of cloning and functional
      characterization of fish antiviral genes is promising in further elucidation of
      the fish antiviral response. The adaptive immune system of fish utilizes cellular
      components more or less similar to mammals. Teleost fish produce IgM as a primary
      antibody response and lack isotype switching to mount virus-specific antibodies
      during the infection process. Despite this, the development of successful fish
      rhabdoviral vaccines suggest that vaccination may prove to be an effective way of
      promoting fish adaptive immune responses to viruses. This paper reviews the bony
      fish antiviral response with specific discussion on the evolutionary mechanisms
      that allow aquatic viruses to co-exist with their host. Detailed aspects of the
      teleost type I IFN system are also addressed.

PMID- 20797791
TI  - Review of 'emerging' organic contaminants in biosolids and assessment of
      international research priorities for the agricultural use of biosolids.
AB  - A broad spectrum of organic chemicals is essential to modern society. Once
      discharged from industrial, domestic and urban sources into the urban wastewater
      collection system they may transfer to the residual solids during wastewater
      treatment and assessment of their significance and implications for beneficial
      recycling of the treated sewage sludge biosolids is required. Research on organic
      contaminants (OCs) in biosolids has been undertaken for over thirty years and the
      increasing body of evidence demonstrates that the majority of compounds studied
      do not place human health at risk when biosolids are recycled to farmland.
      However, there are 143,000 chemicals registered in the European Union for
      industrial use and all could be potentially found in biosolids. Therefore, a
      literature review of 'emerging' OCs in biosolids has been conducted for a
      selection of chemicals of potential concern for land application based upon human
      toxicity, evidence of adverse effects on the environment and endocrine
      disruption. To identify monitoring and research priorities the selected chemicals
      were ranked using an assessment matrix approach. Compounds were evaluated based
      upon environmental persistence, human toxicity, evidence of bioaccumulation in
      humans and the environment, evidence of ecotoxicity and the number and quality of
      studies focussed on the contaminant internationally. The identified chemicals of
      concern were ranked in decreasing order of priority: perfluorinated chemicals
      (PFOS, PFOA); polychlorinated alkanes (PCAs), polychlorinated naphthalenes
      (PCNs); organotins (OTs), polybrominated diphenyl ethers (PBDEs), triclosan
      (TCS), triclocarban (TCC); benzothiazoles; antibiotics and pharmaceuticals;
      synthetic musks; bisphenol A, quaternary ammonium compounds (QACs), steroids;
      phthalate acid esters (PAEs) and polydimethylsiloxanes (PDMSs). A number of
      issues were identified and recommendations for the prioritisation of further
      research and monitoring of 'emerging' OCs for the agricultural use of biosolids
      are provided. In particular, a number of 'emerging' OCs (PFOS, PFOA and PCAs)
      were identified for priority attention that are environmentally persistent and
      potentially toxic with unique chemical properties, or are present in large
      concentrations in sludge, that make it theoretically possible for them to enter
      human and ecological food-chains from biosolids-amended soil.

PMID- 20797793
TI  - Perception of Munker-White illusion in 4-8-month-old infants.
AB  - There have been numerous studies of the Munker-White illusion, but few have
      focused on the perceptual development of it in human infants. Therefore, this
      study explores the perceptual development of the Munker-White illusion in
      infants. In this study, we created two kinds of Munker-White illusion patterns
      that had different subjective saturation, and investigated infants' preference
      for these two kinds of patterns. Previous studies have shown that infants had a
      preference for high colorimetric saturation stimuli. Therefore, if infants could
      perceive the Munker-White illusion, we postulated that they would show a
      preference for stimuli that have high subjective saturation. In experiment 1, 4-8
      month-old infants showed a preference for the stimuli that had a higher
      subjective saturation. In experiment 2, we confirmed that the preference shown in
      experiment 1 was not dependent on the difference of the 'color area ratio' that
      existed in the stimuli of experiment 1. Our results suggest that 4-8-month-old
      infants can perceive Munker-White illusion.

PMID- 20797794
TI  - Clinical and non-clinical depressive symptoms and risk of long-term sickness
      absence among female employees in the Danish eldercare sector.
AB  - BACKGROUND: Depression has a high point and life time prevalence and is a major
      cause of reduced work ability and long-term sickness absence (LTSA). Less is
      known of the extent to which non-clinical depressive symptoms are related to the
      risk of LTSA. The aim of this study was to investigate how non-clinical and
      clinical depressive symptoms are prospectively associated to subsequent LTSA.
      METHODS: In a cohort study of 6985 female employees from the Danish eldercare
      sector depressive symptoms were measured by the Major Depression Inventory (MDI)
      and scores (0-50) were divided into groups of 0-4, 5-9, 10-14, 15-19, >=20 points
      and clinical depression. Data was linked to a national register with information
      on LTSA (>=3 weeks). Hazard ratios (HR) for LTSA during a 1-year follow-up were
      calculated by Cox's proportional hazards model. RESULTS: Compared to the
      reference group (0-4) the HR was stronger for each subsequent group: MDI scores
      of 5-9: HR=1.07 (95% CI: 0.93-1.24); 10-14: 1.38 (1.15-1.66); 15-19: 1.54 (1.20
      1.98); >=20: 1.96 (1.45-2.64); clinical depression: 2.32 (1.59-3.38); after
      adjustment for previous LTSA, age, family status, smoking, leisure time physical
      activity, BMI, and occupational group. LIMITATIONS: Missing information on the
      cause of sickness absence and prevalent somatic illness. CONCLUSION: A clear dose
      response relationship exists between increasing depressive symptoms and risk of
      LTSA. The adverse effect of non-clinical depressive symptoms on LTSA already
      manifests itself at relatively low scores. CLINICAL RELEVANCE: this study
      illustrates the valuable information of considering the whole continuum of
      depressive symptoms.

PMID- 20797795
TI  - Childhood history of behavioral inhibition and comorbidity status in 256 adults
      with social phobia.
AB  - BACKGROUND: Behavioral inhibition (BI), a heritable temperament, predisposes one
      to an increased risk of social phobia. Recent investigations have reported that
      BI may also be a precursor to anxiety as well as depressive and alcohol-related
      disorders, which are frequently comorbid with social phobia. In the present
      study, we explored the relationship between BI and psychiatric disorders in 256
      adults with a primary diagnosis of social phobia. METHODS: BI severity was
      retrospectively assessed with the Retrospective Self-Report of Inhibition (RSRI).
      The severity of social phobia and the presence of comorbid diagnoses were
      evaluated with the Liebowitz Social Anxiety Scale (LSAS) and the Mini
      International Neuropsychiatric Interview, respectively. RESULTS: The RSRI score
      was significantly and positively correlated with both the LSAS score and the
      occurrence of a major depressive disorder. No significant association was found
      with other anxiety and substance-related disorders. LIMITATION: The assessment of
      BI was retrospective and self-reported. CONCLUSION: A childhood history of BI was
      associated with an increased risk of depressive comorbidity in social phobia.

PMID- 20797796
TI  - Ignoring irrelevant stimuli in latent inhibition and Stroop paradigms: the
      effects of schizotypy and gender.
AB  - Latent inhibition (LI), poor evidence of learning following preexposure to a task
      irrelevant stimulus, reflects the ability to ignore inconsequential events.
      Stroop interference represents a failure to inhibit processing of a task
      irrelevant word when it is incongruent with the required naming of the word's
      print color. The apparent commonality between the two effects is in contradiction
      to the literature, which indicates that LI is affected by schizotypy and
      schizophrenia, and perhaps gender, while Stroop interference generated by the
      trial-to-trial procedure is unaltered by those variables. In the present
      experiment, low schizotypal healthy males, but not females, exhibited LI. The
      same groups did not differ on Stroop interference. The results are discussed in
      terms of different processing requirements for task-irrelevant stimuli that are
      an integral part of the task-relevant target stimulus (as in Stroop) or separated
      from it in space (as in LI).

PMID- 20797797
TI  - Psychomotor function and response inhibition in chronic fatigue syndrome.
AB  - Most research points to cognitive slowing in chronic fatigue syndrome (CFS),
      although there have been negative reports. The present study is one of few that
      examines fine motor processing and the inhibition of automatic responses in a
      well-characterised CFS population. A total of 35 female CFS patients without
      current major depression and 25 female controls performed two computerised figure
      copying tasks. The cognitive and fine motor processing of visual-spatial
      information was measured by recording reaction time (RT) and movement time (MT),
      respectively. The inhibition of automatic responses was assessed by introducing
      'conflicting patterns' (i.e., patterns that were difficult to draw from the
      preferred left to right). A multivariate general linear model was adopted for the
      statistical analysis of the movement recordings. As a result, CFS was
      significantly associated with longer RT and MT in the pooled and in the task
      specific analyses. However, there was no interaction between disease status and
      conflicting character of the patterns. In conclusion, these performance data on
      the figure-copying tasks provide confirmatory evidence for psychomotor slowing in
      CFS, but not for a disturbed inhibition of automatic responses. Computerised
      figure-copying tasks may be promising tools for use in neurobiological research
      and clinical trials in CFS.

PMID- 20797798
TI  - "Real world" functioning in schizophrenia patients and healthy adults: assessing
      validity of the Multidimensional Scale of Independent Functioning.
AB  - As treatment efforts to enhance cognitive abilities in schizophrenia increase, so
      too does the need for a critical appraisal of instruments that measure
      functionality and adjustment to community living. The Multidimensional Scale of
      Independent Functioning (MSIF; Jaeger et al., 2003) is a promising instrument
      that assesses functionality in relation to different life settings, performance
      levels, responsibilities and environmental supports. However, its applicability
      to the schizophrenia population has been questioned because relevant data are
      scarce. This study provides descriptive and validity-related information by
      reporting MSIF scores in healthy community-dwelling adults (n=71) and in
      schizophrenia outpatients (n=156). Results show that healthy adults performed
      within defined "normal" ranges in most MSIF domains in comparison to
      schizophrenia patients who showed moderate to severe impairments. Moreover, the
      MSIF distinguished between the two groups with accuracy rates as high as 98% and
      effect sizes (standardized mean group difference) above 2.0 in almost all
      domains. Accordingly, the MSIF is a potentially valuable measure of community
      independence that can inform treatment initiatives and may be adaptable to the
      evaluation of functionality changes over time. The unique structure and content
      of information obtained by the MSIF makes it a candidate for inclusion in studies
      aimed at developing a new generation of instruments for the assessment of real
      world functioning in schizophrenia.

PMID- 20797799
TI  - Decreased aldosterone in the plasma of suicide attempters with major depressive
      disorder.
AB  - Hormones and neurobiological factors may be regulated differently in suicidal
      versus non-suicidal depressive patients. There is currently limited knowledge
      about the relation of substances in the Renin-Angiotensin-Aldosterone system to
      depression and suicidality. We therefore investigated whether plasma levels of
      renin and aldosterone differ between suicide attempters, non-suicidal depressive
      patients and healthy controls. Furthermore, we analyzed the relation of renin and
      aldosterone to psychiatric symptoms in the patients. Suicidal patients with MDD,
      adjustment disorder and dysthymia, as well as two control groups consisting of
      non-suicidal MDD patients and healthy subjects, were rated using the
      Comprehensive Psychopathological Rating Scale (CPRS), including the Montgomery
      Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA).
      Plasma samples were frozen immediately after collection and stored at -80 degrees
      C for 5-18years. Aldosterone and renin levels were analyzed using radioactive-
      and chemiluminescent immunoassays. We found that suicide attempters with MDD had
      significantly lower plasma levels of aldosterone than the other patient groups,
      as well as than the healthy controls. Moreover, increasing severity of
      psychiatric symptoms was associated with lower aldosterone levels in the suicide
      attempters with MDD. Non-suicidal patients with MDD did not differ significantly
      compared to healthy controls with respect to aldosterone and renin levels. These
      findings may indicate that low aldosterone levels could be a marker of
      suicidality in patients with MDD.

PMID- 20797800
TI  - Earning and learning among Australian community residents with psychiatric
      disorders.
AB  - At a population level the extent that psychiatric disorders and other health
      conditions disrupt participation in education and employment is rarely considered
      simultaneously and remains largely unknown. This is an important issue because
      policy makers are as concerned with educational attainment, school to work
      transitions, and workforce skills, as they are with overall labour force
      participation. We investigated earning or learning, and educational attainment,
      among Australian community residents by age group and by category of psychiatric
      disorder. Data files were provided by the Australian Bureau of Statistics (ABS)
      from a population survey conducted in 2003 using a multi-stage probability sample
      (N=23,787). Adults with schizophrenia, depression, and anxiety disorders were
      compared to (1) working age adults with other non-psychiatric health conditions
      and disabilities; and (2) healthy adults of working age. Participation in formal
      education and employment was extensively disrupted by all health conditions and
      by psychiatric disorders in particular. The extent of career-related disruption
      provides benchmarks for policy makers and service providers attempting to
      increase participation in formal education and in the labour force.

PMID- 20797801
TI  - Gender differences in the prevalence of diabetes mellitus in chronic hospitalized
      patients with schizophrenia on long-term antipsychotics.
AB  - Gender-specific relationships between diabetes mellitus (DM) and schizophrenia
      have previously received little systematic study. The results showed that the
      overall DM prevalence was 20% with rates of 17% (58/343) in males and 27%
      (46/172) in females (p<0.01). Furthermore, increased body mass index (BMI),
      abdominal obesity and antipsychotic types were predictors of diabetes in these
      chronic schizophrenic patients.

PMID- 20797802
TI  - Differences in self-reported decision-making styles in stimulant-dependent and
      opiate-dependent individuals.
AB  - In light of the growing evidence of altered decision-making in addiction we
      assessed decision-making styles in drug-dependent individuals using the Melbourne
      Decision-Making Questionnaire (MDMQ). Consistent with the literature on
      laboratory tests of decision-making, we found that stimulant users reported less
      competent and more maladaptive decision-making styles compared with controls.

PMID- 20797803
TI  - Glyburide increases risk in patients with diabetes mellitus after emergent
      percutaneous intervention for myocardial infarction--a nationwide study.
AB  - BACKGROUND: Sulfonylureas have been linked to an increased cardiovascular risk by
      inhibition of myocardial preconditioning. Whether individual sulfonylureas affect
      outcomes in diabetic patients after emergent percutaneous coronary intervention
      for myocardial infarction is unknown. METHODS: All Danish patients receiving
      glucose-lowering drugs admitted with myocardial infarction between 1997 and 2006
      who underwent emergent percutaneous coronary intervention were identified from
      national registers. Multivariable Cox proportional hazards models were used to
      analyze the risk of cardiovascular mortality and morbidity associated with
      sulfonylureas. RESULTS: A total of 926 patients were included and 163 (17.6%)
      patients died during the first year of which 155 (16.7%) were cardiovascular
      deaths. The most common treatment was sulfonylureas which were received by 271
      (29.3%) patients, and 129 (13.9%) received metformin. Cox proportional hazard
      regression analyses adjusted for age, sex, calendar year, comorbidity and
      concomitant pharmacotherapy showed an increased risk of cardiovascular mortality
      (hazard ratio [HR] 2.91, 95% confidence interval [CI] 1.26-6.72 ; p=0.012),
      cardiovascular mortality and nonfatal myocardial infarction (HR 2.69 , 95% CI
      1.21-6.00; p=0.016), and all-cause mortality (HR 2.46, 95% CI 1.11-5.47;
      p=0.027), respectively, with glyburide compared to metformin. CONCLUSIONS:
      Glyburide is associated with increased cardiovascular mortality and morbidity in
      patients with diabetes mellitus undergoing emergent percutaneous coronary
      intervention after myocardial infarction. Early reperfusion therapy is the
      mainstay in modern treatment of myocardial infarction and the time may have come
      to discard glyburide in favour of sulfonylureas that do not appear to confer
      increased cardiovascular risk.

PMID- 20797804
TI  - Prevalence and antimicrobial resistance of Salmonella in retail foods in northern
      China.
AB  - A total of 387 retail meat, seafood and milk powder samples were collected from
      nine cities in northern China in 2005 and screened for the presence of
      Salmonella. Salmonella strains isolated were subjected to serotyping and
      antimicrobial susceptibility testing. Salmonella was isolated from 81 (20.9%,
      81/387) samples and classified into 23 serotypes. The isolates were frequently
      resistant to sulfamethoxazole (86.4%), sulfamethoxazole/trimethoprim (48.1%),
      nalidixic acid (30.9%), tetracycline (19.8%), carboxybenzylpenicillin (17.3%),
      amoxicillin (17.3%) and ampicillin (16.0%). The multiple resistance (resistance
      to >= 3 antibiotics) was found in 29.6% (n = 24) isolates. Additionally, 4
      isolates from chicken displayed the ACSSuTNx profile, resistant to ampicillin,
      chloramphenicol, streptomycin, sulfonamide, tetracycline and nalidixic acid, in
      particular, strain HBS084 showing the resistance to as many as 20 antibiotics.
      Salmonella from chicken showed the higher frequency of antimicrobial resistance.
      Our findings indicate that in northern China food products of animal origin can
      be a source of exposure for consumers to multiresistant Salmonella strains.

PMID- 20797805
TI  - Unraveling the genetic predisposition of ribavirin-induced anaemia.

PMID- 20797806
TI  - X-ray microtomography characterization of porosity, permeability and reactive
      surface changes during dissolution.
AB  - Numerical programs for simulating flow and reactive transport in porous media are
      essential tools for predicting reservoir properties changes triggered by CO(2)
      underground injection. At reservoir scale, meshed models in which equations are
      solved assuming that constant macroscopic properties can be defined in each
      cells, are widely used. However, the parameterization of the dissolution
      precipitation problem and of the feedback effects of these processes on the flow
      field is still challenging. The problem arises from the mismatch between the
      scales at which averaged parameters are defined in the meshed model and the scale
      at which chemical reactions occur and modify the pore network geometry. In this
      paper we investigate the links between the dissolution mechanisms that control
      the porosity changes and the related changes of the reactive surface area and of
      the permeability. First, the reactive surface area is computed from X-ray
      microtomography data obtained before and after a set of dissolution experiments
      of pure calcite rock samples using distinctly different brine-CO(2) mixtures
      characterizing homogeneous to heterogeneous dissolution regimes. The results are
      used to validate the power law empirical model relating the reactive surface area
      to porosity proposed by Luquot and Gouze (2009). Second, we investigate the
      spatial distribution of the effective hydraulic radius and of the tortuosity, two
      structural parameters that control permeability, in order to explain the
      different porosity-permeability relationships observed for heterogeneous and
      homogeneous dissolution regimes. It is shown that the increase of permeability is
      due to the decrease of the tortuosity for homogeneous dissolution, whereas it is
      due to the combination of tortuosity decrease and hydraulic radius increase for
      heterogeneous dissolution. For the intermediate dissolution regime, identified to
      be the optimal regime for increasing permeability with small changes in porosity,
      the increase of permeability results from a large increase in the mean effective
      hydraulic radius of the sample.

PMID- 20797807
TI  - Synthesis and anti-prion activity evaluation of aminoquinoline analogues.
AB  - Transmissible spongiform encephalopathies form a group of neurodegenerative
      diseases that affect humans and other mammals. They occur when the native prion
      protein is converted into an infectious isoform, the scrapie PrP, which
      aggregates, leading to neurodegeneration. Although several compounds were
      evaluated for their ability to inhibit this conversion, there is no effective
      therapy for such diseases. Previous studies have shown that antimalarial
      compounds, such as quinolines, possess anti-scrapie activity. Here, we report the
      synthesis and evaluate the effect of aminoquinoline derivatives on the
      aggregation of a prion peptide. Our results show that 4-amino-7-chloroquinoline
      and N-(7-chloro-4-quinolinyl)-1,2-ethanediamine inhibit the aggregation
      significantly. Therefore, such aminoquinolines might be considered as candidates
      for the further development of therapeutics to prevent the development of prion
      diseases.

PMID- 20797808
TI  - Synthesis and pharmacological evaluation of clubbed isopropylthiazole derived
      triazolothiadiazoles, triazolothiadiazines and mannich bases as potential
      antimicrobial and antitubercular agents.
AB  - A series of novel clubbed Isopropylthiazole derivatives triazolothiadiazines 2a
      g, dihydro triazolothiadiazoles 3a-g, thioxotriazoles 4a-d, triazolothiadiazole
      5, arylideneamino triazolethiones 7a-h and oxadiazolethiones 11a-b were
      synthesized and characterized by IR, (1)H NMR, (13)C NMR, elemental and mass
      spectral analysis. These compounds were evaluated for their preliminary in vitro
      antibacterial, antifungal and antitubercular activity against Mycobacterium
      tuberculosis H(37)Rv strain by broth dilution assay method. All the compounds
      exhibited moderate to significant antibacterial and antifungal activities.
      Results of the antitubercular screening against M. tuberculosis H(37)Rv showed
      compounds 7c and 7d exhibited good antitubercular activity (MIC 4 and 8 MUg/mL)
      respectively, when compared with first line drug such as isoniazid (0.25 MUg/mL).

PMID- 20797810
TI  - Biosorption of uranium by chemically modified Rhodotorula glutinis.
AB  - The present paper reports the biosorption of uranium onto chemically modified
      yeast cells, Rhodotorula glutinis, in order to study the role played by various
      functional groups in the cell wall. Esterification of the carboxyl groups and
      methylation of the amino groups present in the cells were carried out by methanol
      and formaldehyde treatment, respectively. The uranium sorption capacity increased
      31% for the methanol-treated biomass and 11% for the formaldehyde-treated biomass
      at an initial uranium concentration of 140 mg/L. The enhancement of uranium
      sorption capacity was investigated by Fourier transform infrared (FTIR)
      spectroscopy analysis, with amino and carboxyl groups were determined to be the
      important functional groups involved in uranium binding. The biosorption
      isotherms of uranium onto the raw and chemically modified biomass were also
      investigated with varying uranium concentrations. Langmuir and Freundlich models
      were well able to explain the sorption equilibrium data with satisfactory
      correlation coefficients higher than 0.9.

PMID- 20797811
TI  - Effect of an anterior-sloped brace joint on anterior tibial translation and axial
      tibial rotation: a motion analysis study.
AB  - BACKGROUND: Anterior tibial translation and axial tibial rotation are major
      biomechanical factors involved in anterior cruciate ligament injuries. This study
      sought to evaluate a brace prototype designed with an anterior-sloped joint, in
      terms of its efficacy in attenuating anterior tibial translation and axial tibial
      rotation during landing, using a motion analysis approach. METHODS: Ten healthy
      male subjects performed single-leg landing tasks from a 0.6-m height with and
      without the brace prototype. Ground reaction force and kinematics data were
      obtained using a motion-capture system and force-plates. Anterior tibial
      translation and axial tibial rotation were determined based on tibial and femoral
      marker reference frames. Vertical and anterior-posterior ground reaction forces,
      hip, knee and ankle joint range-of-motions and angular velocities, anterior
      tibial translation and axial tibial rotation were compared between unbraced and
      braced conditions using Wilcoxon signed-rank test. FINDINGS: We found no
      significant difference in peak vertical and anterior-posterior ground reaction
      forces (p=0.770 and p=0.332 respectively) between unbraced and braced conditions.
      Knee joint range-of-motion and angular velocity were lower (p=0.037 and p=0.038
      respectively) for braced condition than unbraced condition. Anterior tibial
      translation and axial tibial rotation were reduced (p=0.027 and p=0.006
      respectively) in braced condition, compared to unbraced condition.
      INTERPRETATION: The anterior-sloped brace joint helps to attenuate anterior
      tibial translation and axial tibial rotation present in the knee joint during
      landing. It is necessary to test the brace prototype in a sporting population
      with realistic sports landing situations in order to assess its effectiveness in
      lowering anterior cruciate ligament injury risk.

PMID- 20797812
TI  - The association between lower extremity energy absorption and biomechanical
      factors related to anterior cruciate ligament injury.
AB  - BACKGROUND: Greater total energy absorption by the lower extremity musculature
      during landing may reduce stresses placed on capsuloligamentous tissues with
      differences in joint contributions to energy absorption potentially affecting
      anterior cruciate ligament injury risk. However, the relationships between energy
      absorption and prospectively identified biomechanical factors associated with non
      contact anterior cruciate ligament injury have yet to be demonstrated. METHODS:
      Sagittal plane total, hip, knee and ankle energy absorption, and peak vertical
      ground reaction force, anterior tibial shear force, knee flexion and knee valgus
      angles, and internal hip extension and knee varus moments were measured in 27
      individuals (14 females, 13 males) performing double leg jump landings.
      Correlation coefficients assessed the relationships between energy absorption
      during three time intervals (initial impact phase, terminal phase, and total
      landing) and biomechanical factors related to anterior cruciate ligament injury.
      FINDINGS: More favorable values of biomechanical factors related to non-contact
      anterior cruciate ligament injury were associated with: 1) Lesser total
      (R(2)=0.178-0.558), hip (R(2)=0.229-0.651) and ankle (R(2)=0.280), but greater
      knee (R(2)=0.147) energy absorption during the initial impact phase; 2) Greater
      total (R(2)=0.170-0.845), hip (R(2)=0.599), knee (R(2)=0.236-0.834), and ankle
      (R(2)=0.276) energy absorption during the terminal phase of landing; and 3)
      Greater knee (R(2)=0.158-0.709), but lesser hip (R(2)=0.309) and ankle
      (R(2)=0.210-0.319) energy absorption during the total landing period.
      INTERPRETATION: These results suggest that biomechanical factors related to
      anterior cruciate ligament injury are influenced by both the magnitude and timing
      of lower extremity energy absorption during landing.

PMID- 20797813
TI  - Implications of high altitude desert dust transport from Western Sahara to Nile
      Delta during biomass burning season.
AB  - The air over major cities and rural regions of the Nile Delta is highly polluted
      during autumn which is the biomass burning season, locally known as black cloud.
      Previous studies have attributed the increased pollution levels during the black
      cloud season to the biomass or open burning of agricultural waste, vehicular,
      industrial emissions, and secondary aerosols. However, new multi-sensor
      observations (column and vertical profiles) from satellites, dust transport
      models and associated meteorology present a different picture of the autumn
      pollution. Here we show, for the first time, the evidence of long range transport
      of dust at high altitude (2.5-6 km) from Western Sahara and its deposition over
      the Nile Delta region unlike current Models. The desert dust is found to be a
      major contributor to the local air quality which was previously considered to be
      due to pollution from biomass burning enhanced by the dominant northerly winds
      coming from Europe.

PMID- 20797814
TI  - Professional autonomy in 21st century healthcare: nurses' accounts of clinical
      decision-making.
AB  - Autonomy in decision-making has traditionally been described as a feature of
      professional work, however the work of healthcare professionals has been seen as
      steadily encroached upon by State and managerialist forces. Nursing has faced
      particular problems in establishing itself as a credible profession for reasons
      including history, gender and a traditional subservience to medicine. This paper
      reports on a focus group study of UK nurses participating in post-qualifying
      professional development in 2008. Three groups of nurses in different specialist
      areas comprised a total of 26 participants. The study uses accounts of decision
      making to gain insight into contemporary professional nursing. The study also
      aims to explore the usefulness of a theory of professional work set out by Jamous
      and Peloille (1970). The analysis draws on notions of interpretive repertoires
      and elements of narrative analysis. We identified two interpretive repertoires:
      'clinical judgement' which was used to describe the different grounds for making
      judgements; and 'decision-making' which was used to describe organisational
      circumstances influencing decision-making. Jamous and Peloille's theory proved
      useful for interpreting instances where the nurses collectively withdrew from the
      potential dangers of too extreme claims for technicality or indeterminacy in
      their work. However, their theory did not explain the full range of accounts of
      decision-making that were given. Taken at face value, the accounts from the
      participants depict nurses as sometimes practising in indirect ways in order to
      have influence in the clinical and bureaucratic setting. However, a focus on
      language use and in particular, interpretive repertoires, has enabled us to
      suggest that despite an overall picture of severely limited autonomy, nurses in
      the groups reproduced stories of the successful accomplishment of moral and
      influential action.

PMID- 20797815
TI  - The effect of shear stress on protein conformation: Physical forces operating on
      biochemical systems: The case of von Willebrand factor.
AB  - Macromolecules and cells exposed to blood flow in the circulatory tree experience
      hydrodynamic forces that affect their structure and function. After introducing
      the general theory of the effects of shear forces on protein conformation,
      selected examples are presented in this review for biological macromolecules
      sensitive to shear stress. In particular, the biochemical effects of shear stress
      in controlling the von Willebrand Factor (VWF) conformation are extensively
      described. This protein, together with blood platelets, is the main actor of the
      early steps of primary haemostasis. Under the effect of shear forces >30 dyn/cm2,
      VWF unfolding occurs and the protein exhibits an extended chain conformation
      oriented in the general direction of the shear stress field. The stretched VWF
      conformation favors also a process of self aggregation, responsible for the
      formation of a spider web network, particularly efficient in the trapping process
      of flowing platelets. Thus, the effect of shear stress on conformational changes
      in VWF shows a close structure-function relationship in VWF for platelet adhesion
      and thrombus formation in arterial circulation, where high shear stress is
      present. The investigation of biophysical effects of shear forces on VWF
      conformation contributes to unraveling the molecular interaction mechanisms
      involved in arterial thrombosis.

PMID- 20797816
TI  - pH-dependent interaction of psychotropic drug with glycerophospholipid monolayers
      studied by the Langmuir technique.
AB  - We have earlier investigated the interaction of the antipsychotic drugs
      chlorpromazine(CPZ) and olanzapine(OLP) with glycerophospholipid monolayers.
      These experiments were carried out at high and low temperatures and showed that
      OLP had a more pronounced effect on the packing of the phospholipid (PL)
      monolayers than CPZ. At pH 7.36, where OLP consists of one positive and one
      neutral species. In the present work we have studied the interaction of the drugs
      with monolayers of PLs by the Langmuir technique at pH 6.00 and 10.00 at 37
      degrees C. The PLs were palmitoylphosphatidyl-choline(DPPC), 1-stearoyl-2
      arachinodonoylphoshatidylcholine(SAPC),dipalmitoylphosphatidyl-serine(DPPS) and 1
      palmitoyl-2-oleoylphosphatidylserine(POPS). OLP has a pKa around 7.4, with one
      neutral and one positive species at pH 6.00 and pH 10.00, respectively. CPZ has
      pKa value around 9.4, and is positively charged at pH 6.00 and neutral at pH
      10.00. Our studies revealed that the surface area of DPPC with CPZ in the
      subphase did not change at pH 6.00. In contrast, OLP increased the mean molecular
      area(MMA) of DPPC at pH 6.00, while CPZ caused distinct increase in MMA on the
      monolayer packing of all the other PLs, including monolayers of DPPC at pH 10.00.
      OLP, increased MMA of all PLs at both pHs. Further, OLP increased MMA of DPPC (pH
      10.00), SAPC (pH 10.00), DPPS (pH 6.00) and POPS (pH 6.00) at 30mN/m, the
      expected MMA of biological membranes. CPZ had the more pronounced effect at lift
      off and gave an effect of the monolayers with negatively charged head groups in
      accordance our earlier experiments. However, CPZ affected the packing of the SAPC
      monolayer both at pH 6.00 and 10.00, and DPPC at pH 10.00. Both these PLs have
      neutral choline head group. Our results suggest that both drugs intercalate in
      the PL monolayers, and that the intercalation might involve electrostatic
      interaction with the head groups or hydrophobic interaction with the acyl chains
      of the PLs, or both. Probably the drugs intercalate to different extents
      depending on charge of both the drugs and the PL head groups. Our investigation
      may suggest that the interaction of CPZ and OLP with membrane PLs could be linked
      to both the psychotropic and the side effects.

PMID- 20797817
TI  - MicroRNA expression and its implication for the diagnosis and therapeutic
      strategies of gastric cancer.
AB  - MicroRNAs (miRNAs) are a recently discovered category of small RNA molecules that
      regulate gene expression at the post-transcriptional level. Accumulating evidence
      indicated that miRNAs are aberrantly expressed in a variety of human cancers and
      crucial to tumorigenesis. We herein provide a brief review of miRNA biogenesis,
      function, deregulation and their possible role as oncogenes or tumor suppressors
      in the pathogenesis of gastric cancer. The role of miRNAs in the carcinogenic
      effect of Helicobacter pylori infection was also discussed. Finally, we comment
      on the potential role of miRNAs in improving the current management of gastric
      cancer.

PMID- 20797818
TI  - Development of a dispersive liquid-liquid microextraction method for iron
      speciation and determination in different water samples.
AB  - A novel, simple and efficient method for the iron (Fe) speciation and
      determination in different water samples was developed using dispersive liquid
      liquid microextraction (DLLME) technique followed by spectrophotometric analysis.
      The procedure is based on complexation of Fe(II) with O-phenanthroline (O-Phen),
      the subsequent ion-association formation with picrate anion, then extraction of
      the complex using DLLME technique. Some important parameters such as the type and
      volume of extraction and dispersive solvents as well as the extraction time were
      investigated and optimized in detail. Under the optimum conditions, the
      calibration graphs were linear over the range of 0.025-1.0 MUg mL(-1) with limit
      of detection of 7.5 MUg L(-1). Relative standard deviation for five replicate
      determinations of Fe at 0.2 MUg mL(-1) concentration level was calculated to be
      1.2%. Average recoveries for spiked samples were determined to be between 90% and
      108%. The method was applied to water samples and parenteral solutions and the
      amounts of Fe found in these samples using the proposed method were similar with
      those obtained by a standard method.

PMID- 20797819
TI  - Activity-related summation of pain and functional disability in patients with
      whiplash injuries.
AB  - This study investigated the relation between repetition-induced summation of
      activity-related pain (RISP) and indicators of functional disability in a sample
      of 62 individuals who had sustained whiplash injuries. Participants completed
      measures of pain severity, pain catastrophizing, fear of movement and depression
      prior to lifting a series of 36 weighted canisters. An index of RISP was computed
      as the increase in pain reported by participants over successive lifts of the
      weighted canisters. Measures of functional disability included physical lifting
      tolerance, self-reported disability and perceived work demands. Regression
      analyses revealed that the index of RISP accounted for significant variance in
      measures of lifting tolerance and perceived work demands, even when controlling
      for age, sex and pain severity. The index of RISP was also significantly
      correlated with pain catastrophizing and pain duration. The discussion addresses
      the mechanisms by which physiological and psychological factors might contribute
      to increases in pain during repeated physical activity. Discussion also addresses
      whether RISP might represent a risk factor for problematic recovery outcomes
      following whiplash injury.

PMID- 20797820
TI  - The dawn of the yawn: is yawning a warning? Linking neurological disorders.
AB  - Yawning continues to pose as a scientist's conundrum. Evidence is presented of
      yawning and contagious yawning in a number of different neurological disorders.
      Explanations are discussed in the context of disparate neurological disorders
      together with proposals for how theses findings may be linked. Thus, greater
      understanding of yawning and of neurological disorders may be achieved by
      exploring common neuro-chemical pathways and the involvement of neurotransmitters
      that are implicated in these different disorders. Finally, contagious yawning is
      discussed in the context of the susceptibility of persons and the similarity this
      presents with our understanding of the mechanisms involved in hypnosis.

PMID- 20797821
TI  - Butyrylcholinesterase in metabolic syndrome.
AB  - Butyrylcholinesterase may have a role in a number of metabolic functions and
      could affect the expression of insulin resistance syndrome. We present our
      integrated work using clinical, biochemical and bioinformatic approaches to
      delineate the possible function of this enzyme. Initially, we constructed a
      phylogenic tree with nucleotides and amino acid sequences and showed the
      existence of similar sequences in bacteria, plants and in other animals. We also
      demonstrated a possible pathogenic role for BChE in the common existence of
      insulin resistance, type 2 diabetes and Alzheimer's disease by in silico method
      and followed it up with a diabetic mouse study where cognition was slowed along
      with changes in BChE levels. In the next group of in silico studies, we employed
      THEMATICS method to identify the amino acids at the active site and later
      performed docking studies with drugs. THEMATICS predicted two clusters of
      ionisable amino acid residues that are in proximity: one with two residues and
      another with 11 showed perturbation in the THEMATICS curves. Using ISIS/Draw
      2.5SP4, ARGUSLAB 4.0.1 and HEX 5.1. software. 3-D ligands were docked with BChE
      motif (from PDB). We did not find any of the ligands studied with significant
      docking distance, indicating they did not have direct interaction with the active
      site. Subsequently we performed in silico studies to compare the secondary
      structure and domain of BChE. Protein-protein interaction showed the following
      intersections with BChE UBE21, CHAT, APOE, AATF, DF ALDH9A1, PDHX, PONI PSME3 and
      ATP6VOA2. The integrative physiological roles of proteins with poorly known
      functions can be approached by generating leads in silico, which can be studied
      in vivo, setting into movement an iterative process.

PMID- 20797822
TI  - Finishing diet, temperament and lairage time effects on carcass and meat quality
      traits in steers.
AB  - Sixty Hereford (H) and Braford (B: 3/8 Zebu and 5/8 H) steers were finished on:
      D1) rangeland plus corn grain (1% of live weight) (H n=15, B n=15); and D2) high
      quality pasture (H n=15, B n=15) to study the effect of diet, temperament and
      lairage time on carcass and meat quality. Steers were slaughtered the same day in
      two groups, spending 15 and 3h in pens, respectively (50% from D1, 50% from D2 in
      each group). Animals from D1 had better carcass performance without effect of the
      diet on meat quality. Regardless of breed, calmer steers showed higher average
      daily gain and lower shear force values. Carcasses from animals in the long
      lairage group had a better rate of pH decline and more tender meat, suggesting
      that more than 3h preslaughter time should be necessary to rest and recover,
      mainly depending on lairage conditions.

PMID- 20797823
TI  - Distribution of prostate sentinel nodes: a SPECT-derived anatomic atlas.
AB  - PURPOSE: The randomized Radiation Therapy Oncology Group 94-13 trial revealed
      that coverage of the pelvic lymph nodes in high-risk prostate cancer confers an
      advantage (progression-free survival and biochemical failure) in patients with
      >=15% risk of lymph node involvement. To facilitate an improved definition of the
      adjuvant target volume, precise knowledge regarding the location of the relevant
      lymph nodes is necessary. Therefore, we generated a three-dimensional sentinel
      lymph node atlas. METHODS AND MATERIALS: In 61 patients with high-risk prostate
      cancer, a three-dimensional visualization of sentinel lymph nodes was performed
      using a single photon emission computed tomography system after transrectal
      intraprostatic injection of 150 to 362 (median 295) mega becquerel (MBq)
      (99m)Technetium-nanocolloid (1.5-3 h after injection) followed by an anatomic
      functional image fusion. RESULTS: In all, 324 sentinel nodes in 59 of 61 patients
      (96.7%) were detected, with 0 to 13 nodes per patient (median 5, mean 5.3). The
      anatomic distribution of the sentinel nodes was as follows: external iliac 34.3%,
      internal iliac 17.9%, common iliac 12.7%, sacral 8.6%, perirectal 6.2%, left
      paraaortic 5.3%, right paraaortic 5.3%, seminal vesicle lymphatic plexus 3.1%,
      deep inguinal 1.5%, superior rectal 1.2%, internal pudendal 1.2%, perivesical
      0.9%, inferior rectal 0.9%, retroaortic 0.3%, superficial inguinal 0.3%, and
      periprostatic 0.3%. CONCLUSIONS: The distribution of sentinel nodes as detected
      by single photon emission computed tomography imaging correlates well with the
      distribution determined by intraoperative gamma probe detection. A lower
      detection rate of sentinels in close proximity to the bladder and seminal
      vesicles is probably caused by the radionuclide accumulation in the bladder. In
      regard to intensity-modulated radiotherapy techniques, the presented anatomic
      atlas may allow optimized target volume definitions.

PMID- 20797824
TI  - A randomized trial (Irish clinical oncology research group 97-01) comparing short
      versus protracted neoadjuvant hormonal therapy before radiotherapy for localized
      prostate cancer.
AB  - PURPOSE: To examine the long-term outcomes of a randomized trial comparing short
      (4 months; Arm 1) and long (8 months; Arm 2) neoadjuvant hormonal therapy before
      radiotherapy for localized prostate cancer. METHODS AND MATERIALS: Between 1997
      and 2001, 276 patients were enrolled and the data from 261 were analyzed. The
      stratification risk factors were prostate-specific antigen level >20 ng/mL,
      Gleason score>=7, and Stage T3 or more. The intermediate-risk stratum had one
      factor and the high-risk stratum had two or more. Staging was done from the bone
      scan and computed tomography findings. The primary endpoint was biochemical
      failure-free survival. RESULTS: The median follow-up was 102 months. The overall
      survival, biochemical failure-free survival. and prostate cancer-specific
      survival did not differ significantly between the two treatment arms, overall or
      at 5 years. The cumulative probability of overall survival at 5 years was 90%
      (range, 87-92%) in Arm 1 and 83% (range, 80-86%) in Arm 2. The biochemical
      failure-free survival rate at 5 years was 66% (range, 62-71%) in Arm 1 and 63%
      (range, 58-67%) in Arm 2. CONCLUSION: No statistically significant difference was
      found in biochemical failure-free survival between 4 months and 8 months of
      neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer.

PMID- 20797826
TI  - The role of forensic anthropology in Disaster Victim Identification (DVI).
AB  - This paper briefly describes Disaster Victim Identification (DVI) and reviews the
      history of the use of forensic anthropology in the identification process. The
      potential contributions made by forensic anthropology are illustrated through the
      presentation of a case study. In February 2009 the state of Victoria in south
      eastern Australia experienced the most devastating bushfires in its history,
      resulting in catastrophic loss of life and public and private property. Within
      48h of the disaster, forensic teams including pathologists, odontologists and
      anthropologists assembled at the Victorian Institute of Forensic Medicine in
      Melbourne to begin the task of identifying the deceased. This paper reviews the
      part played by forensic anthropologists in the identification process and
      outlines the important contribution anthropologists can make to DVI, especially
      at the scene, in the mortuary and in the reconciliation process. The
      anthropologist's experience with differentially preserved human remains meant
      they played an important role identifying and recovering heavily fragmentary
      human skeletal remains, differentiating human from non-human remains,
      establishing basic biological information such as the sex and age of the
      individuals and confirming or denying the possibility of re-associating body
      parts for release to families.

PMID- 20797825
TI  - Associations between abstinence in adolescence and economic and educational
      outcomes seven years later among high-risk youth.
AB  - AIM: In this study, we investigated the relationship between abstinence and long
      term educational and economic outcomes among a sample of high-risk youth.
      METHODS: Multivariable regression models were used to estimate associations
      between abstinence and outcomes among a sample of 13-17 year-olds referred to
      group homes in Los Angeles in 1999-2000 and followed for 87 months afterwards.
      Abstinence was measured during the first year of the study. We considered
      differential effects based on the duration of abstinence (12 vs. 6 months) and
      type of abstinence (all substances vs. use of alcohol and/or marijuana) on three
      87-month outcomes: having received a high-school diploma or equivalent by age 20,
      institutionalization in the past 90 days, and total legitimate income for the
      past 90 days. RESULTS: Abstinence from all substances for 12 months was
      associated with positive long-term educational and economic outcomes relative to
      using any drug during the same time interval. Abstaining from all substances for
      12 months was also associated with an increased likelihood of being a legitimate
      wage earner and decreased likelihood of being institutionalized relative to using
      only alcohol and/or marijuana during that time interval. No effect on long-term
      outcomes was seen among youth who abstained for only 6 months relative to those
      who used drugs during this interval, or for youth who used only alcohol and/or
      marijuana over 12 months vs. those who used other drugs during this interval.
      CONCLUSIONS: The results presented here justify continued and expanded efforts to
      promote long periods of abstinence from all drugs for high-risk youth.

PMID- 20797827
TI  - Epidemiology of cerebral palsy in El-Kharga District-New Valley (Egypt).
AB  - Cerebral palsy (CP) is the most frequent cause of motor handicap among children.
      The present door to door (every door) study was conducted in El-Kharga District
      New Valley to estimate the epidemiology of CP among children. Each child was
      subjected to complete medical and neurological examination to detect cases with
      CP. These diseased children were subjected to meticulous neurological and medical
      assessment, brain MRI, EEG and Stanford Binet (4th edition). It was found that 52
      out of 25,540 children had CP yielding prevalence rate of 2.04/1000 (95% CI: 1.48
      2.59) of living births. Mean age of children with CP, was 7.17+/-4.38years. The
      order of frequency of different subtypes of CP was as follows, 65.4% had spastic
      type, 26.9% mixed type and 3.8% for each ataxic and dyskinetic types of CP. The
      frequency of risk factors of CP in our study is prenatal complications (cyanosis,
      preterm, jaundice, birth weight and obstructed labor of mothers), first baby,
      similar condition and recurrent abortions.

PMID- 20797828
TI  - CD4+ CD25(high) regulatory T cell in childhood ocular myasthenia gravis.
AB  - Dysfunction of CD4(+)CD25(+) regulatory T cell (Treg) has been demonstrated to
      play an important role in the development of autoimmune myasthenia gravis. This T
      cell subset, which has potent regulatory properties against immune response, has
      been reported to have a numerical or functional defect in patients with
      myasthenia gravis. We examined various T cell subsets, including
      CD4(+)CD25(+)Treg in peripheral blood mononuclear cells using flow cytometry in a
      pediatric patient suffering from ocular myasthenia gravis. Contrary to previous
      reports, the percentage of CD4(+)CD25(+)Treg in peripheral blood decreased
      significantly after successful treatment with prednisolone. This discrepancy
      could result from diversity within the immunopathogenesis of myasthenia gravis
      and may underpin a particular subgroup of myasthenia gravis seen in the East
      Asian pediatric population.

PMID- 20797829
TI  - Acoustic effects of lamotrigine in pediatric patients with epilepsy.
AB  - The aim of this study was to investigate the acoustic effects of lamotrigine in
      pediatric epileptic patients. Newly diagnosed 52 pediatric epileptic patients
      were assessed standard speech test through a Computerized Speech Lab applied
      before the beginning of therapy with lamotrigine and 2months after dosage had
      been stabilized. The voice onset times for /t/, /k(h)/, /p'/ and /t'/ after the
      therapy and those for /p/, /k/, /p(h)/, /t(h)/ and /k'/ was not affected. Total
      durations for all stop consonants did not change significantly except that lenis
      /p/ and /k/ increased significantly (P<0.05). No noteworthy alteration was
      observed for mean pitch and speaking rate of counting 1-10. Vowel formants and
      precise articulation rate remained the same. In conclusion, no significant
      effects of lamotrigine on speech were found in this study. Lamotrigine is safe
      for acoustic function in pediatric patients.

PMID- 20797830
TI  - High-resolution in vivo diffusion tensor imaging of the injured cat spinal cord
      using self-navigated, interleaved, variable-density spiral acquisition (SNAILS
      DTI).
AB  - Diffusion tensor magnetic resonance imaging (DTI) is useful for studying the
      microstructural changes in the spinal cord following traumatic injury; however,
      image quality is generally poor due to the small size of the spinal cord,
      physiological motion and susceptibility artifacts. Self-navigated, interleaved,
      variable-density spiral diffusion tensor imaging (SNAILS-DTI) is a distinctive
      pulse sequence that bypasses many of the challenges associated with DTI of the
      spinal cord, particularly if imaging gradient hardware is of conventional
      quality. In the current study, we have demonstrated the feasibility of
      implementing SNAILS-DTI on a clinical 3.0-T MR scanner and examined the effect of
      navigator filter parameters on image quality and reconstruction time. Results
      demonstrate high-quality, high-resolution (546 MUm*546 MUm) in vivo DTI images of
      the cat spinal cord after traumatic spinal cord injury.

PMID- 20797831
TI  - N-Acetyl peak in MR spectra of intracranial metastatic mucinous adenocarcinomas.
AB  - Absence of N-acetylaspartate (NAA) is one important diagnostic criterion of MR
      spectroscopy (MRS) that may suggest that an intracranial mass lesion is a
      metastasis. We report two cases of histopathology-confirmed intracranial
      metastatic mucinous adenocarcinoma, which predominantly showed a large metabolite
      peak at 2.0 ppm, mimicking an NAA peak of normal brain tissue. This finding could
      be of help in the interpretation of MRS in cases of intracranial enhancing mass
      lesions, metastases or gliomas.

PMID- 20797832
TI  - Magnetic resonance image enhancement using stochastic resonance in Fourier
      domain.
AB  - OBJECTIVE: In general, low-field MRI scanners such as the 0.5- and 1-T ones
      produce images that are poor in quality. The motivation of this study was to
      lessen the noise and enhance the signal such that the image quality is improved.
      Here, we propose a new approach using stochastic resonance (SR)-based transform
      in Fourier space for the enhancement of magnetic resonance images of brain
      lesions, by utilizing an optimized level of Gaussian fluctuation that maximizes
      signal-to-noise ratio (SNR). MATERIALS AND METHODS: We acquired the T1-weighted
      MR image of the brain in DICOM format. We processed the original MR image using
      the proposed SR procedure. We then tested our approach on about 60 patients of
      different age groups with different lesions, such as arteriovenous malformation,
      benign lesion and malignant tumor, and illustrated the image enhancement by using
      just-noticeable difference visually as well as by utilizing the relative
      enhancement factor quantitatively. RESULTS: Our method can restore the original
      image from noisy image and optimally enhance the edges or boundaries of the
      tissues, clarify indistinct structural brain lesions without producing ringing
      artifacts, as well as delineate the edematous area, active tumor zone, lesion
      heterogeneity or morphology, and vascular abnormality. The proposed technique
      improves the enhancement factor better than the conventional techniques like the
      Wiener- and wavelet-based procedures. CONCLUSIONS: The proposed method can
      readily enhance the image fusing a unique constructive interaction of noise and
      signal, and enables improved diagnosis over conventional methods. The approach
      well illustrates the novel potential of using a small amount of Gaussian noise to
      improve the image quality.

PMID- 20797834
TI  - [Postoperative herpetic meningoencephalitis after lumbar surgery: a case report].
AB  - We report a case of a patient with an herpetic meningoencephalitis complicating
      lumbar surgery. A combination of factors like a postoperative sepsis, an abnormal
      MRI, and a positive viral PCR and culture made the diagnosis. A prolonged
      acyclovir treatment was employed with satisfactory results. This case remembers
      us the possibility of herpes reactivation in a stressful situation (including
      surgical stress).

PMID- 20797833
TI  - Using freelisting to understand shared decision making in ADHD: parents' and
      pediatricians' perspectives.
AB  - OBJECTIVE: To compare and contrast notions of ADHD among pediatricians and
      parents of affected children to understand the perspectives they bring to shared
      decision making (SDM). METHODS: In this freelisting study, 60 parents of children
      with ADHD and 30 primary care pediatricians listed words reflecting their
      understanding of (1) Attention Deficit Hyperactivity Disorder (ADHD), (2)
      getting/offering help for ADHD, (3) talking to doctors/families about ADHD, and
      (4) "mental health." Smith's salience score established terms that were salient
      and cultural consensus analysis identified variation within subgroups of
      participants. RESULTS: Parents' terms reflected ADHD's effects on the child and
      family, while clinicians often mentioned school. Lists suggested differing needs
      and goals for clinicians and subgroups of parents in SDM: "time" for clinicians,
      "learning" and "understanding" for non-college educated parents, and "comfort"
      and "relief" for college educated parents. Neither parents nor clinicians framed
      ADHD in the same way as "mental health." CONCLUSION: Parents and clinicians, who
      conceptualize ADHD differently, should negotiate a shared understanding of ADHD
      as a basis for SDM. Treatment discussions should be tailored to encompass
      families' varied emotional and educational needs. PRACTICE IMPLICATIONS:
      Fostering SDM in primary care is consonant with notions of ADHD as distinct from
      mental health.

PMID- 20797835
TI  - [Impact of the hyperthermic intraperitoneal chemotherapy on the fluid
      electrolytes changes and on the acid-base balance].
AB  - BACKGROUND: Hyperthermic intraperitoneal chemoperfusion (HIPEC) is an innovative
      treatment of the peritoneal carcinomatosis with potential iatrogenicity. This
      observational study was designed to improve our understanding of HIPEC's impact
      on the renal and respiratory functions, on temperature, blood cells counts, body
      fluids/electrolytes and acid-base balance. METHODS: We retrospectively analyzed
      the perioperative care of 20 patients that underwent HIPEC with oxaliplatin
      (n=19) and mitomycin C (n=1). The abdominal cavity was filled with the peritoneal
      dialysis fluid with dextrose 5%: volume of 2L/m(2). Follow-up for the study was
      stopped on postoperative day 7. RESULTS: The main changes were appearing just
      after the HIPEC procedure: increased diuresis, lactic acidosis, hyponatremia and
      hyperglycaemia (despite aggressive intravenous insulin therapy). In our series,
      there was no renal failure or impact on blood cells counts until the 7(th) day,
      neither some changes on the arterial blood gases. CONCLUSION: Hyperglycemia might
      explain increased diuresis of lactic acidosis and the rapid installation of
      hyponatremia. Taken together, these results suggest that glycemic control must be
      improved in order to avoid the other metabolic disturbances.

PMID- 20797837
TI  - A method for estimating noise variance of CT image.
AB  - Rank et al. have proposed an algorithm for estimating image noise variance
      composed of the following three steps: the noisy image is first filtered by a
      difference operator; a histogram of local signal variances is then computed; and,
      finally the noise variance is estimated from a statistical evaluation of the
      histogram. We have verified the accuracy of this algorithm on a CT image by
      indirect methods, and have shown that this method is able to estimate CT image
      noise variance with reasonable accuracy, regardless of whether or not the
      noiseless image is uniform. Further, we have proposed a simple alternative method
      for the last two steps of the Rank et al. method. However, one must pay attention
      to the fact that the estimated noise variance will be biased when the nearest two
      pixels are correlated and that this algorithm does not work well if the
      assumption of stationarity of noise components is violated.

PMID- 20797836
TI  - A measure of palliative care in nursing homes.
AB  - CONTEXT: Efforts to improve care for nursing home residents stand to be enhanced
      by measures to assess the degree to which staff provide palliative care. As the
      incidence of death in nursing homes increases with the aging population, the gap
      in measurement must be addressed. To that end, we report the development and
      psychometric testing of a nursing home palliative care survey. OBJECTIVES: The
      purpose of this study was to evaluate the psychometric properties of the
      Palliative Care Survey (PCS) for use in nursing homes. METHODS: Psychometric
      evaluation of the instrument was completed in two phases. Phase 1 focused on
      individual item analyses and subsequent revision or deletion of items, and Phase
      2 evaluated evidence for reliability and validity. Phase 1 included 26 nursing
      homes and staff (n=717), and Phase 2 included 85 nursing homes and staff
      (n=2779). Data were analyzed using item-total correlations, Cronbach's alpha,
      confirmatory factor analysis, and analysis of variance. RESULTS: Support was
      obtained for a 51-item PCS made up of two constructs, Palliative Care Practice
      and Palliative Care Knowledge. CONCLUSION: The PCS measures the extent to which
      the nursing home staff engage in palliative care practices and have knowledge
      consistent with good end-of-life care. Both practice and knowledge are an
      essential foundation to providing good end-of-life care to nursing home
      residents. Efforts to improve care for the dying in nursing homes have been
      slowed by an absence of measurement tools that capture care processes, a gap that
      the PCS reported here helps fill.

PMID- 20797838
TI  - General functioning predicts reward and punishment learning in schizophrenia.
AB  - Previous studies investigating feedback-driven reinforcement learning in patients
      with schizophrenia have provided mixed results. In this study, we explored the
      clinical predictors of reward and punishment learning using a probabilistic
      classification learning task. Patients with schizophrenia (n=40) performed
      similarly to healthy controls (n=30) on the classification learning task.
      However, more severe negative and general symptoms were associated with lower
      reward-learning performance, whereas poorer general psychosocial functioning was
      correlated with both lower reward- and punishment-learning performances. Multiple
      linear regression analyses indicated that general psychosocial functioning was
      the only significant predictor of reinforcement learning performance when
      education, antipsychotic dose, and positive, negative and general symptoms were
      included in the analysis. These results suggest a close relationship between
      reinforcement learning and general psychosocial functioning in schizophrenia.

PMID- 20797839
TI  - A case-control study and meta-analysis of association between a common copy
      number variation of the glutathione S-transferase mu 1 (GSTM1) gene and
      schizophrenia.

PMID- 20797840
TI  - Defining the need for prostate cancer radiotherapy in the general population: a
      criterion-based benchmarking approach.
AB  - AIMS: Determining the appropriate rate of radiotherapy is important for ensuring
      optimal radiotherapy utilisation and accessibility. A criterion-based benchmark
      (CBB) approach was developed as an alternative to evidence-based methods of
      determining the need for radiotherapy in prostate cancer. Our primary objective
      was to determine the initial/lifetime CBB radiotherapy rates in prostate cancer
      and to compare results with evidence-based estimates. Secondary objectives were
      to compare observed radiotherapy rates in Ontario, Canada and the USA with the
      estimated rates. MATERIALS AND METHODS: Benchmarks were defined in Ontario as
      communities in proximity to cancer centres and without long waiting lists.
      Surgical and radiotherapy data, encompassing both external beam radiation and
      brachytherapy, for 1997-2001 were collected for Ontario cancer patients. The
      Surveillance, Epidemiology and End Results (SEER) public use file described
      treatment in the USA. RESULTS: In total, 35 379 cases of prostate cancer were
      diagnosed in Ontario and 93 275 in SEER. CBB estimates of the initial/lifetime
      need for radiotherapy were 37.2% (95% confidence interval: 35.8-38.7) and 59.1%
      (54.3-63.9). Our group's evidence-based estimate (Ebest) rates were 32.3% (28.5
      36.1) and 61.2% (55.6-66.8). Observed initial radiotherapy rates were 28.0% (27.5
      28.4) in Ontario and 37.0% (36.7-37.3) in SEER. In Ontario, the estimated
      lifetime rate was 42.6% (41.2-44.0). CONCLUSIONS: CBB provides a reasonable
      estimate of the need for radiotherapy in prostate cancer. Observed initial
      radiotherapy rates in the USA were concordant with the CBB estimate. The CBB
      suggests a shortfall in radiotherapy utilisation for prostate cancer in Ontario.

PMID- 20797841
TI  - The Physicians' Practice Assessment Questionnaire on asthma and COPD.
AB  - We describe a new tool, the Physicians' Practice Assessment Questionnaire (PPAQ),
      designed for the global self-assessment of implementation of asthma and COPD
      guidelines, as determined by the percentage of patients in whom physicians
      estimate that they implement guidelines key recommendations. Some of its
      properties were assessed by a group of 47 general practitioners (GPs), and test
      retest data were obtained in repeating the questionnaire at a 5-week interval
      without intervention in a sub-group of 28 practitioners. Answers to the various
      questions were globally reproducible. The lowest scores (recommendations
      implemented in less than 50% of their patients) were: 1) for both asthma and
      COPD: referral for patient education, provision of a written action plan and
      regular assessment of inhaler technique, 2) for asthma: referral to a specialist
      for difficult to control asthma or uncertain diagnosis, and 3) for COPD:
      assessment of lung function and disability according to specific criteria and
      referral to a rehabilitation program. The analysis showed sufficient internal
      consistency for both questionnaires (Cronbach alphas 0.7617 for asthma and 0.8317
      for COPD). Pearson's correlations indicated good test-retest (r = 0.6421, p =
      0.0002 for asthma; r = 0.6801, p < 0.0001 for COPD). In conclusion, the PPAQ is a
      new tool to assess implementation of asthma and COPD guidelines; it has the
      potential to identify care gaps that can be specifically targeted for
      intervention.

PMID- 20797842
TI  - Emerging contaminants: nanomaterial fate in landfills.

PMID- 20797843
TI  - First-line therapy with moderate dose capecitabine in metastatic breast cancer is
      safe and active: results of the MONICA trial.
AB  - BACKGROUND: To determine activity and safety of capecitabine at a moderate dose
      of 2000 mg/m(2) as first-line therapy for metastatic breast cancer. METHODS: In
      this prospective phase II trial, patients with HER2-negative metastatic breast
      cancer received first-line capecitabine 2000 mg/m(2) on days 1-14 every 3 weeks.
      The primary aim was to exclude a time to progression (TTP) <6 months. Secondary
      end-points were overall response rate, overall survival (OS), toxicity and
      quality of life. RESULTS: Median age of the 161 included patients was 65 years.
      Median TTP and OS were 7.3 months [95% (confidence interval) CI: 6.2-8.4] and
      17.1 months (95% CI: 14.0-20.3), respectively. An overall response rate of 26.1%,
      including 13 complete remissions was observed. Patients developing grade I-III
      hand-foot syndrome had a significantly longer TTP and OS and patients >65 years
      also achieved a significantly longer TTP. Haematological grade I-IV toxicities
      were leucopenia (64.0%), anaemia (50.9%) and thrombocytopenia (28.0%). Relevant
      non-haematological toxicities were hand-food-syndrome (37.3%), fatigue (34.2%),
      nausea (29.8%) and diarrhoea (20.5%). Quality of life assessment revealed an
      improved emotional function, but worsening of nausea and vomiting from cycle 1
      10. CONCLUSIONS: Capecitabine at a dose of 2000 mg/m(2) is active and safe as
      first-line treatment of patients with metastatic breast cancer.

PMID- 20797844
TI  - An international multicentre validation study of a pain classification system for
      cancer patients.

PMID- 20797845
TI  - The tumour-targeting human L19-IL2 immunocytokine: preclinical safety studies,
      phase I clinical trial in patients with solid tumours and expansion into patients
      with advanced renal cell carcinoma.
AB  - BACKGROUND: L19-IL2, a tumour-targeting immunocytokine composed of the
      recombinant human antibody fragment L19 (specific to the alternatively-spliced
      EDB domain of fibronectin, a well characterised marker of tumour neo-vasculature)
      and of human IL2, has demonstrated strong therapeutic activity in animal cancer
      models. This phase I/II trial was performed to evaluate safety, tolerability,
      recommended phase II dose (RD) and early signs of activity of L19-IL2. PATIENTS
      AND METHODS: Five cohorts of patients with progressive solid tumours (n=21)
      received an intravenous infusion of L19-IL2 (from 5 to 30 Mio IU IL2 equivalent
      dose) on days 1, 3 and 5 every 3 weeks. This treatment cycle was repeated up to
      six times. In the following expansion phase, patients with metastatic renal cell
      carcinoma (RCC) (n=12) were treated at the RD of L19-IL2. Clinical data and
      laboratory findings were analysed for safety, tolerability and activity. RESULTS:
      Preclinical studies in rats and monkeys did not raise any safety concerns. The RD
      was defined to be 22.5 Mio IU IL2 equivalent. Pharmacokinetics of L19-IL2 was
      dose proportional over the tested range, with a terminal half-life of 2-3h.
      Toxicities were manageable and reversible with no treatment-related deaths. We
      observed stable disease in 17/33 patients (51%) and 15/18 with mRCC (83%) after
      two cycles. Median progression-free survival of RCC patients in the expansion
      phase of the study was 8 months (1.5-30.5). CONCLUSIONS: L19-IL2 can be safely
      and repeatedly administered at the RD of 22.5 Mio IU IL2 equivalent in advanced
      solid tumours. Preliminary evaluation suggests clinical activity of L19-IL2 in
      patients with mRCC.

PMID- 20797846
TI  - Psychological consequences of lymphoedema associated with breast cancer: a
      prospective cohort study.
AB  - BACKGROUND: The aim of this prospective cohort study of women attending a
      rehabilitation course at the Dallund Rehabilitation Centre was to explore the
      emotional and psychological aspects of living with lymphoedema, expressed as
      psychological distress, poorer quality of life and poorer self-reported health.
      METHODS: Between November 2002 and January 2007 within the FOCARE study, self
      completed questionnaires were collected 3 weeks before and 6 and 12 months after
      the rehabilitation course to elicit sociodemographic, physical and lifestyle
      information and responses to three psychometric tests. The population consisted
      of 633 women, 125 with and 508 without verified lymphoedema (time since surgery,
      1 month-5 years). The population was reduced to 553 women at the first follow-up
      and 494 at the second. RESULTS: Multivariate analysis showed that, in comparison
      with women without lymphoedema, those with lymphoedema had a 14% higher risk for
      scoring one level higher on the POMS-SF test, a 9% higher probability of scoring
      one point lower on the quality of life scale and a 29% higher likelihood of
      reporting poorer or bad health than women without lymphoedema. These findings
      were seen at all three measurement times. CONCLUSIONS: In this cohort of women
      with breast cancer, women with lymphoedema after surgery for breast cancer had
      significantly worse overall emotional well-being and adjustment to life compared
      to women without lymphoedema.

PMID- 20797847
TI  - Generation of hydrogen rich gas through fluidized bed gasification of biomass.
AB  - The objective of this study was to investigate the process of generating hydrogen
      rich syngas through thermo chemical fluidized bed gasification of biomass. The
      experiments were performed in a laboratory scale externally heated biomass
      gasifier. Rice husk had been taken as a representative biomass and, steam had
      been used as the fluidizing and gasifying media. A thermodynamic equilibrium
      model was used to predict the gasification process. The work included the
      parametric study of process parameters such as reactor temperature and steam
      biomass ratio which generally influence the percentage of hydrogen content in the
      product gas. Steam had been used here to generate nitrogen free product gas and
      also to increase the hydrogen concentration in syngas with a medium range heating
      value of around 12 MJ/Nm3.

PMID- 20797848
TI  - Comparison and optimization of enzymatic saccharification of soybean fibers
      recovered from aqueous extractions.
AB  - Soybean insoluble fractions recovered from aqueous extraction processing (AEP)
      and enzyme-assisted AEP (EAEP) of full-fat soybean flakes (FFSF) and extruded
      FFSF were evaluated as a feedstock for the production of fermentable sugars using
      enzymes. Among the four insoluble fractions (AEP FFSF, EAEP FFSF, AEP extruded
      FFSF and EAEP extruded FFSF), the composition analysis revealed that the one
      recovered from EAEP of extruded FFSF had the highest glucan content, 16% [dry
      basis (db)], as compared to about 10% (db) for the other fractions. Thirty-three
      percent of the initial glucan of the insoluble recovered from AEP and EAEP of
      FFSF were converted into glucose using 33 FPU of Accellerase 1000/g-glucan. This
      saccharification yield was increased to 44% with extruded fibers. The higher
      saccharification yield of 49% was obtained at 45  degrees C, 1% glucan loading,
      and 101 FPU/g-glucan enzymes loading after 27 h of hydrolysis.

PMID- 20797849
TI  - Anaerobic digestion of source-segregated domestic food waste: performance
      assessment by mass and energy balance.
AB  - An anaerobic digester receiving food waste collected mainly from domestic
      kitchens was monitored over a period of 426 days. During this time information
      was gathered on the waste input material, the biogas production, and the
      digestate characteristics. A mass balance accounted for over 90% of the material
      entering the plant leaving as gaseous or digestate products. A comprehensive
      energy balance for the same period showed that for each tonne of input material
      the potential recoverable energy was 405 kWh. Biogas production in the digester
      was stable at 642 m3 tonne(-1) VS added with a methane content of around 62%. The
      nitrogen in the food waste input was on average 8.9 kg tonne(-1). This led to a
      high ammonia concentration in the digester which may have been responsible for
      the accumulation of volatile fatty acids that was also observed.

PMID- 20797850
TI  - Algal biochar--production and properties.
AB  - This study presents baseline data on the physiochemical properties and potential
      uses of macroalgal (seaweed) biochar produced by pyrolysis of eight species of
      green tide algae sourced from fresh, brackish and marine environments. All of the
      biochars produced are comparatively low in carbon content, surface area and
      cation exchange capacity, but high in pH, ash, nitrogen and extractable inorganic
      nutrients including P, K, Ca and Mg. The biochars are more similar in
      characteristics to those produced from poultry litter relative to those derived
      from ligno-cellulosic feedstocks. This means that, like poultry litter biochar,
      macroalgal biochar has properties that provide direct nutrient benefits to soils
      and thereby to crop productivity, and will be particularly useful for application
      on acidic soils. However, macroalgal biochars are volumetrically less able to
      provide the carbon sequestration benefits of the high carbon ligno-cellulosic
      biochars.

PMID- 20797851
TI  - Interaction and nanotoxic effect of ZnO and Ag nanoparticles on mesophilic and
      halophilic bacterial cells.
AB  - The toxicity of two commonly used nanoparticles, silver and zinc oxide on
      mesophilic and halophilic bacterial cells has been investigated. Enterobacter
      sp., Marinobacter sp., Bacillus subtilis, halophilic bacterium sp. EMB4, were
      taken as model systems. The nanotoxicity was more pronounced on Gram negative
      bacteria. ZnO nanoparticles reduced the growth of Enterobacter sp. by 50%, while
      80% reduction was observed in halophilic Marinobacter sp. In case of halophiles,
      this may be attributed to higher content of negatively charged cardiolipins on
      their cell surface. Interestingly, bulk ZnO exerted minimal reduction in growth.
      Ag nanoparticles were similarly cytotoxic. Nanotoxicity towards Gram positive
      cells was significantly less, possibly due to presence of thicker peptidoglycan
      layer. The bacterium nanoparticle interactions were probed by electron microscopy
      and energy dispersive X-ray analysis. The results indicated electrostatic
      interactions between nanoparticles and cell surface as the primary step towards
      nanotoxicity, followed by cell morphological changes, increase in membrane
      permeability and their accumulation in the cytoplasm.

PMID- 20797852
TI  - EDTA-assisted phytoextraction of heavy metals by turfgrass from municipal solid
      waste compost using permeable barriers and associated potential leaching risk.
AB  - A column experiment with horizontal permeable barriers was conducted to
      investigate phytoextraction of heavy metals by Lolium perenne L. from municipal
      solid waste compost following EDTA application, as well as to study the effects
      of L. perenne and permeable barriers on preventing metal from leaching. In
      columns with barriers, EDTA addition yielded maximum concentrations of Cu, Zn and
      Pb of 155, 541 and 33.5 mg kg(-1) in shoot, respectively. This led to 4.2, 2.1
      and 7.4 times higher concentrations of Cu, Zn and Pb compared to treatment with
      no chelating agent, respectively. In treatments with 10 mmol kg(-1) EDTA, the
      barriers reduced leaching of Cu, Zn and Pb by approximately three times,
      respectively, resulting in leaching of total initial Cu, Zn and Pb by 27.3%,
      25.2% and 28.8%, respectively, after four times' irrigation. These results
      indicate that L. perenne and permeable barriers are effective to reduce leaching
      of heavy metals and minimize the risk of contaminating groundwater in EDTA
      enhanced phytoremediation. Thus these findings highlight that turfgrass and
      permeable barriers can effectively prevent metal leaching.

PMID- 20797853
TI  - Effect of autohydrolysis and enzymatic treatment on oil palm (Elaeis guineensis
      Jacq.) frond fibres for xylose and xylooligosaccharides production.
AB  - Oil palm (Elaeis guineensis Jacq.) is one of the most important commercial crops
      for the production of palm oil, which generates 10.88 tons of oil palm fronds per
      hectare of plantation as a by-product. In this study, oil palm frond fibres were
      subjected to an autohydrolysis treatment using an autoclave, operated at 121 
      degrees C for 20-80 min, to facilitate the separation of hemicelluloses. The
      hemicellulose-rich solution (autohydrolysate) was subjected to further hydrolysis
      with 4-16 U of mixed Trichoderma viride endo-(1,4)-beta-xylanases (EC 3.2.1.8)
      per 100 mg of autohydrolysate. Autoclaving of palm fronds at 121 degrees C for 60
      min (a severity factor of 2.40) recovered 75% of the solid residue, containing
      57.9% cellulose and 18% Klason lignin, and an autohydrolysate containing 14.94%
      hemicellulose, with a fractionation efficiency of 49.20%. Subsequent enzymatic
      hydrolysis of the autohydrolysate with 8 U of endoxylanase at 40  degrees C for
      24 h produced a solution containing 17.5% xylooligosaccharides and 25.6% xylose.
      The results clearly indicate the potential utilization of oil palm frond, an
      abundantly available lignocellulosic biomass for the production of xylose and
      xylooligosaccharides which can serve as functional food ingredients.

PMID- 20797854
TI  - Wastewater treatment efficiency of a multi-media biological aerated filter (MBAF)
      containing clinoptilolite and bioceramsite in a brick-wall embedded design.
AB  - A multi-media biological aerated filter (MBAF) with clinoptilolite media was used
      to treat synthetic wastewater. Coal ash bioceramsite with supplemental metallic
      iron was added to the clinoptilolite media of MBAFs in a brick-wall embedded
      design. Performance parameters, such as hydraulic, organic, N and P loading
      capacity and microbial community composition were studied for different quantity
      of supplemental metallic iron contained in three MBAFs. The MBAFs with more
      metallic iron were found to have superior hydraulic and organic loading, and
      higher N and P capacities. COD, NH3-N and TP removal dropped by 7-10%, 6-7% and 4
      5%, respectively, with when hydraulic loading was raised from 2.8 to 7.5 m3 m(-2)
      d(-1). NH3-N removal also decreased 8-9% when ammonia loading was elevated from
      0.078 to 0.156 kg NH3-N m(-3) d(-1). Real-time PCR revealed a relatively stable
      bacterial community composed primarily of eubacteria that formed after an initial
      120 d operational period. Doubling the amount of metallic iron in the
      bioceramsite media resulted in a twofold increase of eubacteria in the MBAF, but
      a decrease in the ratio of anaerobic ammonia-oxidizing bacteria to total
      bacteria.

PMID- 20797855
TI  - PKI-179: an orally efficacious dual phosphatidylinositol-3-kinase
      (PI3K)/mammalian target of rapamycin (mTOR) inhibitor.
AB  - A series of mono-morpholino 1,3,5-triazine derivatives (8a-8q) bearing a 3-oxa-8
      azabicyclo[3.2.1]octane were prepared and evaluated for PI3-kinase/mTOR activity.
      Replacement of one of the bis-morpholines in lead compound 1 (PKI-587) with 3-oxa
      8-azabicyclo[3.2.1]octane and reduction of the molecular weight yielded 8m (PKI
      179), an orally efficacious dual PI3-kinase/mTOR inhibitor. The in vitro
      activity, in vivo efficacy, and PK properties of 8m are discussed.

PMID- 20797856
TI  - Indoloditerpenes from an algicolous isolate of Aspergillus oryzae.
AB  - Two new indoloditerpene derivatives asporyzin A (1) and asporyzin B (2), one new
      indoloditerpene asporyzin C (3), and three known related indoloditerpenes JBIR-03
      (4), emindole SB (5), and emeniveol (6) were isolated from an endophytic fungus
      Aspergillus oryzae, isolated from the marine red alga Heterosiphonia japonica.
      Their structures were unambiguously established by spectroscopic techniques. In
      addition, all the isolates were evaluated preliminarily for insecticidal and
      antimicrobial activities in order to probe into their chemical defensive
      function. Compound 4 was more active against brine shrimp than the others, and 3
      possessed potent activity against Escherichia coli.

PMID- 20797857
TI  - 7-O-Arylmethylgalangin as a novel scaffold for anti-HCV agents.
AB  - In spite of potent antiviral activity, suboptimal physicochemical properties of
      aryl diketo acids (ADKs) necessitates modification of the core 1,3-diketo acid
      functionality into a novel scaffold. As the metal-binding affinity of the diketo
      acid is the key to the antiviral activity of ADKs, we anticipated 3,5-dihydroxy-4
      oxo arrangement of galangin scaffold would serve as an excellent mimic for the
      diketo acid functionality. In this study, through synthesis and biological
      evaluation of various galangin derivatives, we have shown that the diketo acid
      functionality can be successfully replaced with the galangin scaffold by specific
      combination of the substituents to result in identification of a novel galangin
      derivative (3s) with anti-HCV activity (EC(50)=0.9 MUM) comparable to the ADK
      counterpart.

PMID- 20797858
TI  - Synthesis of aminoquinazoline derivatives and their antiproliferative activities
      against melanoma cell line.
AB  - The synthesis of a novel series of aminoquinazoline derivatives 1a-r and their
      antiproliferative activities against A375 human melanoma cell line were
      described. Among them, six compounds showed superior antiproliferative activities
      to Sorafenib as a reference compound. In particular, the representative compound
      1q bearing chromen-4-one moiety exhibited excellent antiproliferative activity
      (IC(50)=0.006 MUM) and good selectivity over HS27 fibroblast cell line.

PMID- 20797859
TI  - Design, synthesis and docking studies on phenoxy-3-piperazin-1-yl-propan-2-ol
      derivatives as protein tyrosine phosphatase 1B inhibitors.
AB  - A series of substituted phenoxy-3-piperazin-1-yl-propan-2-ols has been
      synthesized and evaluated for PTP1B inhibitory activity in vitro and for
      antidiabetic activity in vivo. Two molecules viz. 4a and 5b showed PTP1B
      inhibition of 31.58% and 35.90% at 100 MUM concentration. The compound 4a also
      showed 40.3% normalization of plasma glucose levels at 100mg/kg in Sugar-loaded
      model (SLM) and 32% activity in Streptozodocin model (STZ). The docking studies
      of these molecules revealed that hydrogen bond formation with Arg221 is important
      for activity.

PMID- 20797860
TI  - 99mTc/Re complexes based on flavone and aurone as SPECT probes for imaging
      cerebral beta-amyloid plaques.
AB  - Two (99m)Tc/Re complexes based on flavone and aurone were tested as potential
      probes for imaging beta-amyloid plaques using single photon emission computed
      tomography. Both (99m)Tc-labeled derivatives showed higher affinity for Abeta(1
      42) aggregates than did (99m)Tc-BAT. In sections of brain tissue from an animal
      model of AD, the Re-flavone derivative 9 and Re-aurone derivative 19 intensely
      stained beta-amyloid plaques. In biodistribution experiments using normal mice,
      (99m)Tc-labeled flavone and aurone displayed similar radioactivity
      pharmacokinetics. With additional modifications to improve their brain uptake,
      (99m)Tc complexes based on the flavone or aurone scaffold may serve as probes for
      imaging cerebral beta-amyloid plaques.

PMID- 20797861
TI  - Hos1 is a lysine deacetylase for the Smc3 subunit of cohesin.
AB  - Chromosome cohesion is a cell-cycle-regulated process in which sister chromatids
      are held together from the time of replication until the time of separation at
      the metaphase-to-anaphase transition, ensuring accurate chromosome segregation [1
      9]. Chromosome cohesion is established during S phase, and this process requires
      the four subunits of the cohesin complex (Smc1, Smc3, Mcd1/Scc1, and Irr1/Scc3)
      and the acetyltransferase Eco1 [10-13]. Acetylation of Smc3 by Eco1 at two
      evolutionarily conserved lysine residues promotes cohesion establishment during S
      phase in budding yeast and humans [14-16]. Here we report that Hos1, a member of
      the evolutionarily conserved class I histone deacetylase family, acts as a
      deacetylase for Smc3 in S. cerevisiae. We examine the Smc3 acetylation level in
      nine histone deacetylase deletion strains and find that the acetylation level is
      increased specifically in a hos1Delta strain post-S phase. Coimmunoprecipitation
      experiments show that Hos1 interacts with Smc3 and that the interaction is most
      pronounced as cells reach anaphase. We provide direct evidence that Hos1 can
      deacetylate Smc3 and retains a soluble pool of deacetylated Smc3. Overexpression
      of Hos1 results in less acetylation of Smc3 and cohesion defects in both WT and
      eco1 mutant strains; mutation of the Hos1 active site abolishes the defects. Hos1
      may help to maintain a pool of unacetylated Smc3 that can be used for new
      chromosome cohesion.

PMID- 20797862
TI  - The Mon1-Ccz1 complex is the GEF of the late endosomal Rab7 homolog Ypt7.
AB  - Rab GTPases coordinate membrane fusion reactions [1]. Rab-GDP requires a guanine
      nucleotide exchange factor (GEF) for its conversion to the active GTP form. It
      then binds to effectors such as multimeric tethering complexes and supports
      fusion [2]. GTPase-activating proteins (GAPs) promote GTP hydrolysis to
      inactivate the Rab. GEFs are thus critical activators of fusion reactions [3, 4].
      The Rab GEF family is diverse, ranging from multimeric complexes [5] to monomeric
      GEFs [6-9]. At the late endosome, Rab7 activation is critical for endosomal
      maturation. The yeast Rab7 homolog Ypt7 binds to the homotypic fusion and protein
      sorting (HOPS) complex [10, 11]. Its subunit Vps39/Vam6 has been proposed as a
      GEF for Ypt7 [12] and the Rag GTPase Gtr1 [13], but other genetic evidence has
      implicated the endosomal protein Ccz1 as a GEF for Ypt7 [14]. Ccz1 and its
      binding partner Mon1 have been linked to endosomal transport and maturation [15
      20]. We now provide evidence that the dimeric Mon1-Ccz1 complex is the Rab7/Ypt7
      GEF. The Mon1-Ccz1 complex, but neither protein alone, counteracts GAP function
      in vivo, rescues in vitro fusion of vacuoles carrying Ypt7-GDP, and promotes
      nucleotide exchange on Ypt7 independently of Vps39/HOPS. Our data indicate that
      the Mon1-Ccz1 complex triggers endosomal maturation by activating Ypt7 on late
      endosomes.

PMID- 20797863
TI  - Drosophila TRPA1 channel is required to avoid the naturally occurring insect
      repellent citronellal.
AB  - Plants produce insect repellents, such as citronellal, which is the main
      component of citronellal oil. However, the molecular pathways through which
      insects sense botanical repellents are unknown. Here, we show that Drosophila use
      two pathways for direct avoidance of citronellal. The olfactory coreceptor OR83b
      contributes to citronellal repulsion and is essential for citronellal-evoked
      action potentials. Mutations affecting the Ca(2+)-permeable cation channel TRPA1
      result in a comparable defect in avoiding citronellal vapor. The TRPA1-dependent
      aversion to citronellal relies on a G protein (Gq)/phospholipase C (PLC)
      signaling cascade rather than direct detection of citronellal by TRPA1. Loss of
      TRPA1, Gq, or PLC causes an increase in the frequency of citronellal-evoked
      action potentials in olfactory receptor neurons. Absence of the Ca(2+)-activated
      K(+) channel (BK channel) Slowpoke results in a similar impairment in citronellal
      avoidance and an increase in the frequency of action potentials. These results
      suggest that TRPA1 is required for activation of a BK channel to modulate
      citronellal-evoked action potentials and for aversion to citronellal. In contrast
      to Drosophila TRPA1, Anopheles gambiae TRPA1 is directly and potently activated
      by citronellal, thereby raising the possibility that mosquito TRPA1 may be a
      target for developing improved repellents to reduce insect-borne diseases such as
      malaria.

PMID- 20797864
TI  - Mitotic kinesin CENP-E promotes microtubule plus-end elongation.
AB  - Centromere protein CENP-E is a dimeric kinesin (Kinesin-7 family) with critical
      roles in mitosis, including establishment of microtubule (MT)-chromosome linkage
      and movement of mono-oriented chromosomes on kinetochore microtubules for proper
      alignment at metaphase [1-9]. We performed studies to test the hypothesis that
      CENP-E promotes MT elongation at the MT plus ends. A human CENP-E construct was
      engineered, expressed, and purified, and it yielded the CENP-E-6His dimeric motor
      protein. The results show that CENP-E promotes MT plus-end-directed MT gliding at
      11 nm/s. The results from real-time microscopy assays indicate that 60.3% of
      polarity-marked MTs exhibited CENP-E-promoted MT plus-end elongation. The MT
      extension required ATP turnover, and MT plus-end elongation occurred at 1.48
      MUm/30 min. Immunolocalization studies revealed that 80.8% of plus-end-elongated
      MTs showed CENP-E at the MT plus end. The time dependence of CENP-E-promoted MT
      elongation in solution best fit a single exponential function (k(obs) = 5.1 s(
      1)), which is indicative of a mechanism in which alpha,beta-tubulin subunit
      addition is tightly coupled to ATP turnover. Based on these results, we propose
      that CENP-E, as part of its function in chromosome kinetochore-MT linkage, plays
      a direct role in MT elongation.

PMID- 20797866
TI  - Shod landing provides enhanced energy dissipation at the knee joint relative to
      barefoot landing from different heights.
AB  - Athletic shoes can directly provide shock absorption at the foot due to its
      cushioning properties, however it remains unclear how these shoes may affect the
      level of energy dissipation contributed by the knee joint. This study sought to
      investigate biomechanical differences, in terms of knee kinematics, kinetics and
      energetics, between barefoot and shod landing from different heights. Twelve
      healthy male recreational athletes were recruited and instructed to perform
      double-leg landing from 0.3-m and 0.6-m heights in barefoot and shod conditions.
      The shoe model tested was Brooks Maximus II. Markers were placed on the subjects
      based on the Plug-in Gait Marker Set. Force-plates and motion-capture system were
      used to capture ground reaction force (GRF) and kinematics data respectively. 2*2
      ANOVA (barefoot/shod condition*landing height) was performed to examine
      differences in knee kinematics, kinetics and energetics between barefoot and shod
      conditions from different landing heights. Peak GRF was not significantly
      different (p=0.732-0.824) between barefoot and shod conditions for both landing
      heights. Knee range-of-motion, flexion angular velocity, external knee flexion
      moment, and joint power and work were higher during shod landing (p<0.001 to
      p=0.007), compared to barefoot landing for both landing heights. No significant
      interactions (p=0.073-0.933) were found between landing height and barefoot/shod
      condition for the tested parameters. While the increase in landing height can
      elevate knee energetics independent of barefoot/shod conditions, we have also
      shown that the shod condition was able to augment the level of energy dissipation
      contributed by the knee joint, via the knee extensors, regardless of the tested
      landing heights.

PMID- 20797865
TI  - Shadow enhancers foster robustness of Drosophila gastrulation.
AB  - Critical developmental control genes sometimes contain "shadow" enhancers that
      can be located in remote positions, including the introns of neighboring genes
      [1]. They nonetheless produce patterns of gene expression that are the same as or
      similar to those produced by more proximal primary enhancers. It was suggested
      that shadow enhancers help foster robustness in gene expression in response to
      environmental or genetic perturbations [2, 3]. We critically tested this
      hypothesis by employing a combination of bacterial artificial chromosome (BAC)
      recombineering and quantitative confocal imaging methods [2, 4]. Evidence is
      presented that the snail gene is regulated by a distal shadow enhancer located
      within a neighboring locus. Removal of the proximal primary enhancer does not
      significantly perturb snail function, including the repression of neurogenic
      genes and formation of the ventral furrow during gastrulation at normal
      temperatures. However, at elevated temperatures, there is sporadic loss of snail
      expression and coincident disruptions in gastrulation. Similar defects are
      observed at normal temperatures upon reductions in the levels of Dorsal, a key
      activator of snail expression (reviewed in [5]). These results suggest that
      shadow enhancers represent a novel mechanism of canalization whereby complex
      developmental processes "bring about one definite end-result regardless of minor
      variations in conditions" [6].

PMID- 20797867
TI  - Human fetal anatomy of the posterior semimembranosus complex at the knee with
      special reference to the gastrocnemio-semimembranosus bursa.
AB  - There is little information on the fetal anatomy of the posterior semimembranosus
      tendinous complex and its associated bursa. We examined histological sections
      (transverse or sagittal) of the right or left knee in 13 mid-term human fetuses
      (12-25 weeks of gestation). The medial head of the gastrocnemius provided an
      aponeurosis facing or attached to the muscles of the pes anserinus by 12 weeks of
      gestation. The peritendinous tissue of the semimembranosus provided a bursa
      continuous with a laterally extending plate-like tissue by 15 weeks, but
      sometimes the typical bursa was absent. The aponeurosis of the medial head
      consistently accompanied a bursa-like space (false bursa) surrounded by
      heterogenous structures including the popliteus and a wall of the semimembranosus
      bursa. Sagittal sections displayed notches on the medial head surface that
      received the semimembranosus and semitendinosus overriding the medial head of the
      gastrocnemius. In contrast to a real bursa originating from the peritendinous
      tissue of the semimembranosus, a false bursa without a homogeneous wall
      consistently develops at the origin of the medial head of the gastrocnemius. Due
      to mechanical stress from the tendons, the false bursa is likely to develop into
      a structure similar to a real bursa with a synovial lining even if the real bursa
      is absent in the fetus. We hypothesize that the adult gastrocnemio
      semimembranosus bursa, largely or partly, originates from the fetal false bursa.
      Absolute resection of the false bursa is difficult because it is a mere gap
      between normal tissues.

PMID- 20797868
TI  - Synthesis, antimalarial activity, and cellular toxicity of new
      arylpyrrolylaminoquinolines.
AB  - A set of nine new arylpyrrolyl derivatives of 7-chloro-4-aminoquinoline,
      characterized by different substituents on the phenyl ring or different distance
      between the pyrrolic nitrogen and the 4-aminoquinoline, has been synthesized and
      tested for their activity against D-10 (CQ-S) and W-2 (CQ-R) strains of
      Plasmodium falciparum. All compounds exhibited activity against the CQ-S strain
      in the low nM range, comparable to that of chloroquine. Some of them were also
      highly active against the CQ-R strain and not toxic against normal cells. The
      antimalarial activity of this new class of compounds seems to be related to the
      inhibition of heme detoxification process of parasites, as in the case of
      chloroquine.

PMID- 20797869
TI  - Synthesis of cyclic di-nucleotidic acids as potential inhibitors targeting
      diguanylate cyclase.
AB  - Five analogs of cyclic di-nucleotidic acid including c-di-GMP were synthesized
      and evaluated for their biological activities on Slr1143, a diguanylate cyclase
      of Synechocystis sp. Slr1143 was overexpressed from the recombinant plasmid which
      contained the gene of interest and subsequently purified by affinity
      chromatography. A new HPLC method capable of separating the compound and product
      peaks with good resolution was optimized and applied to the analysis of the
      compounds. Results obtained show that cyclic di-inosinylic acid 1b demonstrates a
      stronger inhibition on Slr1143 than c-di-GMP and is a potential inhibitor for
      biofilm formation.

PMID- 20797870
TI  - Chiral switch of enzymatic ketone reduction by addition of gamma-cyclodextrin.
AB  - We report a chiral switch in the configuration of 1-(p-methoxyphenyl)-propan-2
      ol, synthesized in aqueous media by ketoreductase in the presence of high
      concentration of gamma-CD. NMR, ECD and fluorescence spectrometry were used in
      the effort to explain this unexpected effect. A comparison has been made between
      the catalytic activity of the enzyme and alpha-helix content in the conformation
      and it has been observed that enzyme is most active at the maximum alpha-helix
      content. The beta-sheet content and random coil conformation in the enzyme were
      found to be dependent on cyclodextrin concentration.

PMID- 20797871
TI  - Development of a new epidermal growth factor receptor positron emission
      tomography imaging agent based on the 3-cyanoquinoline core: synthesis and
      biological evaluation.
AB  - The epidermal growth factor receptor (EGFR/c-ErbB1/HER1) is overexpressed in many
      cancers including breast, ovarian, endometrial, and non-small cell lung cancer.
      An EGFR specific imaging agent could facilitate clinical evaluation of primary
      tumors and/or metastases. To achieve this goal we designed and synthesized a
      small array of fluorine containing compounds based on a 3-cyanoquinoline core. A
      lead compound, 16, incorporating 2'-fluoroethyl-1,2,3-triazole was selected for
      evaluation as a radioligand based on its high affinity for EGFR kinase
      (IC50=1.81+/-0.18 nM), good cellular potency (IC50=21.97+/-9.06 nM), low
      lipophilicity and good metabolic stability. 'Click' labeling afforded [18F]16 in
      37.0+/-3.6% decay corrected radiochemical yield based on azide [18F]14 and 7% end
      of synthesis (EOS) yield from aqueous fluoride. Compound [18F]16 was obtained
      with >99% radiochemical purity in a total synthesis time of 3 h. The compound
      showed good stability in vivo and a fourfold higher uptake in high EGFR
      expressing A431 tumor xenografts compared to low EGFR expressing HCT116 tumor
      xenografts. Furthermore, the radiotracer could be visualized in A431 tumor
      bearing mice by small animal PET imaging. Compound [18F]16 therefore constitutes
      a promising radiotracer for further evaluation for imaging of EGFR status.

PMID- 20797872
TI  - Efficacy of temoporfin-loaded invasomes in the photodynamic therapy in human
      epidermoid and colorectal tumour cell lines.
AB  - In the case of cutaneous malignant or non-malignant diseases, topical
      photodynamic therapy (PDT) with a temoporfin (mTHPC)-containing formulation would
      be advantageous. Unfortunately, mTHPC is a highly hydrophobic drug with low
      percutaneous absorption and novel mTHPC-loaded invasomes for enhanced skin
      delivery were developed. The purpose of this study was to investigate
      photodynamic efficacy of mTHPC-loaded invasomes in vitro in two cell lines, i.e.
      the human colorectal tumour cell line HT29 and the epidermoid tumour cell line
      A431. Invasomes are vesicles containing besides phospholipids a mixture of
      terpenes or only one terpene and ethanol. Dark toxicity, phototoxicity and
      intracellular localization of mTHPC were studied. Laser scanning microscopy
      indicated perinuclear localization of mTHPC. Results revealed that mTHPC
      invasomes and mTHPC-ethanolic solution used at a 2MUM mTHPC-concentration and
      photoirradiation at 20J/cm(2) were able to reduce survival of HT29 cells and
      especially of A431 cells, being more sensitive to PDT. In contrast to HT29 cells,
      where there was not a significant difference between cytotoxicity of mTHPC
      ethanolic solution and mTHPC-invasomes, in A431 cells mTHPC-invasomes were more
      cytotoxic. Survival of about 16% of A431 cells treated with mTHPC-invasomes is
      very promising, since it demonstrates invasomes' potential to be used in topical
      PDT of cutaneous malignant diseases.

PMID- 20797873
TI  - Enhanced T cell responsiveness to Mycobacterium bovis BCG r32-kDa Ag correlates
      with successful anti-tuberculosis treatment in humans.
AB  - Th1 and Th2 cytokines play key role in protection from and pathogenesis of
      mycobacterial infection and their dynamic changes may predict clinical outcome of
      the patient. Patients with tuberculosis (TB) have a poorer cellular immune
      response to recombinant 32-kDa antigen (Ag) of Mycobacterium bovis (r32-kDa M.
      bovis) than do healthy volunteers. The basis for this observation was studied by
      evaluating the Th1 (gamma interferon [IFN-gamma]) produced in response to the r32
      kDa Ag M. bovis by peripheral blood mononuclear cells (PBMC) from patients with
      pulmonary TB (n=20), extra-pulmonary TB (n=13) and from healthy volunteers (n=9).
      Recombinant 32-kDa M. bovis stimulated PBMC from TB patients produced
      significantly lower levels of IFN-gamma at 0 month, and increased at 2-4, and 6
      months of treatment and were highly significant (p<0.000) compared to the
      responses in controls. The ratios of IFN-gamma to IL-10 were low in patients
      newly diagnosed and improved both during and after treatment. The present study
      concludes that the levels of in vitro response to M. bovis BCG r32-kDa Ag leading
      to the specific release of IFN-gamma increased after anti-tuberculosis treatment
      and seems to reflect the clinical status of the patient, thus reiterating the
      utility of this antigen in T cell based assays as a surrogate marker of cell
      mediated responses.

PMID- 20797874
TI  - Excipient exchange in the comparison of preparations of the same biologic made by
      different manufacturing processes: an exploratory study with recombinant human
      growth hormone (rhGH).
AB  - Demonstrations of bio-similarity between subsequent entry (follow-on) biologics
      and innovator's formulated drug products may depend upon methods that either
      remove excipients completely or allow the exchange of excipients to give
      equivalent formulations. Excipient exchange through dialysis is perhaps the
      simplest of such methods but its use has been hotly debated. This debate, in the
      absence of published data, has relied largely on theoretical considerations. This
      study presents data that indicate that excipient exchange can allow comparisons
      of different formulations of the same therapeutic protein. The use of excipient
      exchange to and from one concentration of mannitol to another or to a mixture of
      glycine and mannitol was reproducibly demonstrated for recombinant human growth
      hormone (rhGH). We show that marketed rhGH products from several different
      manufacturers exhibit differences in conformational stability when compared
      directly. These differences, however, are shown to be the result of differences
      in formulation rather than in the drug substance itself and were removed through
      excipient exchange. The data presented, therefore, also indicate that failure to
      assure a common excipient background can lead to erroneous conclusions about the
      similarities and differences in the physico-chemical properties of two
      preparations of the same therapeutic protein made by different manufacturing
      processes.

PMID- 20797875
TI  - Determinants of infant growth: Evidence from Hong Kong's "Children of 1997" birth
      cohort.
AB  - PURPOSE: A high rate of infant growth may be associated with adult cardiovascular
      disease. We investigated factors associated with infant weight growth in a large
      sample from the recently transitioned population of Hong Kong. METHODS: We used a
      nonlinear shape invariant model with random effects among 5949 term, singletons
      (77% follow-up) from a population-representative Hong Kong Chinese birth cohort
      "Children of 1997" to investigate factors associated with weight growth in the
      first year of life. RESULTS: Overall birth weight was lower but infant growth was
      more rapid than the 2006 WHO standards. Shorter gestation and lower birth order
      were associated with lower birth weight and faster infant growth. Female sex,
      maternal smoking in pregnancy, and a mother born in Hong Kong were associated
      with lower birth weight, but not with faster growth. Higher maternal education
      was associated with faster infant growth, grades 10-11 (1.03, 95% confidence
      interval [CI] = 1.03-1.05), greater than or equal to grade12 (1.07, CI = 1.04
      1.09) compared with less than or equal to grade 9. CONCLUSIONS: Infant growth may
      respond more rapidly to socio-economic development than birth weight. Whether
      mother's education is associated with rapid infant growth via current conditions
      or her own "constitution" is unclear, nevertheless we believe this study
      illustrates the importance of contextually specific research for understanding
      the determinants of population health.

PMID- 20797876
TI  - Exercise and dehydration: A possible role of inner ear in balance control
      disorder.
AB  - To study the effect of exercise and dehydration on the postural sensory-motor
      strategies, 10 sportsmen performed a 45 min-exercise on a cycle ergometer at
      intensity just below the ventilatory threshold without fluid intake. They
      performed, before, immediately and 20 min after exercise, a sensory organization
      test to evaluate balance control in six different sensory situations, that
      combine three visual conditions (eyes open, eyes closed and sway-referenced
      visual surround motion) with two platform conditions (stable platform, sway
      referenced platform motion). Blood samples were collected before and after
      exercise. Exercise induced a mild dehydration, characterized by body mass loss
      and increase in proteinemia. Postural performances decreased immediately after
      exercise, mainly in the standard situation (eyes open, stable visual surround and
      platform) and when only the vestibular cue was reliable (eyes closed and sway
      referenced platform). Moreover, the decreased use of vestibular input was
      correlated with the dehydration level. Finally, postural performances normalized
      20 min after exercise. Even though muscular fatigue could explain the decrease in
      postural performances, vestibular fluid modifications may also be involved by its
      influence on the intralabyrinthine homeostasis, lowering thus the contribution of
      vestibular information on balance control.

PMID- 20797877
TI  - Shoulder arthroplasty in patients aged fifty-five years or younger with
      osteoarthritis.
AB  - BACKGROUND: The younger patient with glenohumeral arthritis presents a challenge
      because of concerns about activity and frequency of failure. The purpose of this
      study was to define the results, complications, and frequency of revision surgery
      in this group. MATERIALS AND METHODS: Between 1986 and 2005, 46 total shoulder
      arthroplasties and 20 hemiarthroplasties were performed in 63 patients who were
      aged 55 years or younger and had chronic shoulder pain due to glenohumeral
      osteoarthritis. All 63 patients had complete preoperative evaluation, operative
      records, and minimum 2-year follow-up (mean, 7.0 years) or follow-up until
      revision. RESULTS: Nine shoulders underwent a revision operation. The implant
      survival rate was 92% (95% confidence interval, 77%-100%) at 10 years for total
      shoulder arthroplasty and 72% (95% confidence interval, 54%-97%) for
      hemiarthroplasty (Kaplan-Meier result). Patients who underwent total shoulder
      arthroplasty had less pain (P = .01), greater active elevation (P = .05), and
      higher satisfaction (P = .05) at final follow-up compared with those who
      underwent hemiarthroplasty. Complete radiographs were available for 47
      arthroplasties with a minimum 2-year follow-up or follow-up until revision (mean,
      6.6 years). More than minor glenoid periprosthetic lucency or a shift in
      component position was present in 10 of 34 total shoulder arthroplasties.
      Moderate to severe glenoid erosion was present in 6 of 13 hemiarthroplasties.
      CONCLUSIONS: This study indicates that there is intermediate- to long-term pain
      relief and improvement in motion with shoulder arthroplasty in young patients
      with osteoarthritis. These results favor total shoulder arthroplasty in terms of
      pain relief, motion, and implant survival.

PMID- 20797878
TI  - Surgical anatomy of the axillary nerve and its implication in the transdeltoid
      approaches to the shoulder.
AB  - BACKGROUND: Traumatic and iatrogenic injuries of the axillary nerve (AN) are
      frequent in clinical practice; nevertheless, its anatomy and its relationships
      with the transdeltoid approaches to the shoulder are not well documented.
      MATERIALS AND METHODS: Anatomic study was performed on 16 shoulders of unembalmed
      cadavers. A proximal humeral internal locking system (PHILOS) plate was placed to
      simulate the osteosynthesis of a fracture of humeral surgical neck. The
      relationships between the plate and the nerve were evaluated. Selective
      dissection of all the nerve branches inside the deltoid muscle was performed.
      RESULTS: The mean distance between the point where the AN entered into the
      deltoid muscle and the humeral head was 5.0 cm, and it was 6.8 cm from the
      acromion. The mean distance between the origins of the anterior and posterior
      branches of the axillary nerve was 5.4 cm. The mean diameter of the AN was 0.57
      cm, the anterior branch diameter was 0.40 cm, of posterior branch diameter was
      0.33 cm, and the teres minor branch diameter was 0.24 cm. The application of the
      PHILOS plate demonstrated that in 100% of cases, the 2 distal holes of the plate
      of those dedicated to the humeral head coincided with the passage of AN.
      DISCUSSION: The different patterns of nerve branches inside the deltoid muscle
      show that the "safe zone" during transdeltoid approaches is the anterior region
      of the deltoid muscle for a maximum of 6.7 cm from the acromion. In addition, the
      insertion of the 2 distal screws of those dedicated to humeral head of the plate
      should be avoided.

PMID- 20797879
TI  - Surgical treatment of clavicular malignancies.
AB  - HYPOTHESIS: Primary and metastatic malignancies of the clavicle are very rare,
      and little literature is available regarding the long-term functional and
      oncologic outcome after surgical treatment. To what advantage or disadvantages
      clavicle reconstruction following claviculectomy will lead is not clear. The
      hypothesis is that there is no advantage of allograft reconstruction over no
      reconstruction in terms of the functional outcome and complications. MATERIALS
      AND METHODS: From 1999 to 2009, 11 patients with clavicular malignancy underwent
      total or subtotal claviculectomy with or without allograft reconstruction.
      Oncologic and functional results were assessed. RESULTS: The average age at time
      of operation was 31.9 years. The mean follow-up time was 42.4 months. Six
      patients had allograft reconstruction after tumor resection, and 5 had
      claviculectomy alone. No local recurrence occurred. The oncologic result was
      continuous disease-free in 5 patients, no evidence of disease in 1, alive with
      disease in 2, and died of disease in 3. Patients with and without allograft
      reconstruction had average Musculoskeletal Tumor Society score of 92.2% vs 96.2%
      and Constant-Murley scores of 84.8 vs 88.8. Patients with allograft
      reconstruction had more complications than patients without reconstruction.
      DISCUSSION: Considering complications, allograft reconstruction does not
      guarantee a satisfied patient. Total or subtotal excisions of the clavicle
      without reconstruction for malignancies are rarely associated with a clinically
      significant loss of function. Furthermore, the average time of full use of upper
      limb was slower in patients with reconstruction compared with those without
      reconstruction. CONCLUSIONS: Clavicular malignancies had poor prognosis, although
      claviculectomy could provide good local tumor control. Allograft reconstruction
      after claviculectomy was not justified for malignancies in terms of its
      functional outcomes as well as complications.

PMID- 20797880
TI  - Acute calcaneus tendon rupture associated with ipsilateral malleolar fracture:
      case report and literature review.
AB  - Malleolar fractures are rarely associated with lesions of the adjacent tendons or
      neurovascular structures. The association of ankle fractures with Achilles tendon
      rupture is even more infrequent, although both of these injuries are very common
      in and of themselves. To our knowledge, fracture of the lateral malleolus in
      association with an acute rupture of the ipsilateral calcaneus tendon has not
      been previously described. In this article, we describe a female patient who
      sustained an acute rupture of the Achilles tendon in conjunction with fracture of
      the ipsilateral lateral malleolus.

PMID- 20797881
TI  - Simultaneous correction of congenital vertical talus and talipes equinovarus
      using the Ponseti method.
AB  - Talipes equinovarus (clubfoot) and congenital vertical talus are commonly seen as
      isolated deformities in the newborn; however, the case that we described in this
      article entailed a classic talipes equino varus on the left and a calcaneovalgus
      on the right. Both deformities were successfully corrected with manipulation
      therapy and, ultimately, surgical release of the tendoAchillis.

PMID- 20797883
TI  - Trans-Atlantic debate: Is a randomised trial necessary to determine whether
      endovascular repair is the preferred management strategy in patients with
      ruptured abdominal aortic aneurysms?

PMID- 20797884
TI  - Leukoencephalopathy with vanishing white matter caused by compound heterozygous
      mutations in mitochondrial complex I NDUFS1 subunit.

PMID- 20797885
TI  - Increase in HDL-C concentration by a dietary portfolio with soy protein and
      soluble fiber is associated with the presence of the ABCA1R230C variant in
      hyperlipidemic Mexican subjects.
AB  - BACKGROUND: A dietary portfolio has been used to reduce blood lipids in
      hyperlipidemic subjects. To increase the effectiveness of these dietary
      treatments in specific populations, it is important to study the genetic
      variability associated with the development of certain types of hyperlipidemias.
      Low plasma high-density lipoprotein cholesterol (HDL-C) levels are the most
      common dyslipidemia in Mexican adults and are coupled with the presence of the
      ABCA1 R230C genotype. Therefore, the aim of this study was to assess the response
      of HDL-C concentration to a dietary portfolio in a group of Mexican
      hyperlipidemic subjects with ABCA1R230C (rs9282541) and R219K (rs2230806)
      polymorphisms. METHODS: Forty-three hyperlipidemic subjects (20 men and 23 women)
      were given a low saturated fat (LSF) diet for one month, followed by a LSF diet
      that included 25g of soy protein and 15g of soluble fiber daily for 2months. We
      analyzed two ABCA1 polymorphisms and studied their association with serum lipids
      before and after treatment. RESULTS: Hyperlipidemic subjects with the ABCA1 R230C
      genotype showed lower HDL-C concentrations at the beginning of the study and were
      better responders to the dietary treatment than subjects with the ABCA1 R230R
      genotype (+4.6% vs. +14.6%) (p=.05). According to gender and the presence of the
      R230C genotype, women responded more significantly to the dietary treatment,
      reflected by an increase of 21.9% in HDL concentration (p=.022), than women with
      R230R genotype who only experienced an increase of 2.7% in HDL-C concentration.
      There was no association between the presence of the ABCA1 R219K variant (p=.544)
      and HDL concentration. CONCLUSION: Hyperlipidemic Mexican subjects with the ABCA1
      R230C genotype showed lower HDL-concentrations and were better responders to
      dietary portfolio treatments for increasing HDL-C concentrations than subjects
      with the R230R genotype.

PMID- 20797887
TI  - Relative frequency of albicans and the various non-albicans Candida spp among
      candidemia isolates from inpatients in various parts of the world: a systematic
      review.
AB  - BACKGROUND: Candidemia is among the leading causes of nosocomial bloodstream
      infections and is associated with significant mortality. Several centers have
      published data regarding the incidence and relative frequency of Candida spp.
      OBJECTIVE: We performed a systematic review to summarize and evaluate the
      available evidence regarding the distribution of the relative frequency of
      Candida spp isolated from blood, according to geographic region and study design,
      during the period 1996 to 2009. METHODS: We searched PubMed and Scopus and
      retrieved 81 relevant articles reporting data on the relative frequency of
      Candida spp. RESULTS: C. albicans was the predominant species in almost all
      studies. The highest proportion of C. albicans was found in North and Central
      Europe and the USA. Non-albicans species were more common in South America, Asia,
      and South Europe. C. glabrata was commonly isolated in the USA and North and
      Central Europe; C. parapsilosis in South America, South Europe, and several parts
      of Asia; and C. tropicalis in South America and Asia. The relative frequency of
      C. krusei was low in all regions. Significant differences were noted depending on
      study design (surveillance study, multicenter or single centre, prospective or
      retrospective) and setting (hospital or intensive care unit). CONCLUSIONS:
      Significant geographic variation is evident among cases of candidemia in
      different parts of the world. Local epidemiological data continue to be of major
      significance.

PMID- 20797886
TI  - The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by
      modulating SR splicing factor phosphorylation.
AB  - Alternative splicing (AS) of pre-mRNA is utilized by higher eukaryotes to achieve
      increased transcriptome and proteomic complexity. The serine/arginine (SR)
      splicing factors regulate tissue- or cell-type-specific AS in a concentration-
      and phosphorylation-dependent manner. However, the mechanisms that modulate the
      cellular levels of active SR proteins remain to be elucidated. In the present
      study, we provide evidence for a role for the long nuclear-retained regulatory
      RNA (nrRNA), MALAT1 in AS regulation. MALAT1 interacts with SR proteins and
      influences the distribution of these and other splicing factors in nuclear
      speckle domains. Depletion of MALAT1 or overexpression of an SR protein changes
      the AS of a similar set of endogenous pre-mRNAs. Furthermore, MALAT1 regulates
      cellular levels of phosphorylated forms of SR proteins. Taken together, our
      results suggest that MALAT1 regulates AS by modulating the levels of active SR
      proteins. Our results further highlight the role for an nrRNA in the regulation
      of gene expression.

PMID- 20797888
TI  - [Reirradiation in primary or secondary brain tumors].
AB  - The purpose of this review was to analyze data available on reirradiation for
      high-grade glioma or brain metastasis. This reirradiation can be 3D conformal or
      stereotactic. There are no randomized trials. No definitive recommendations can
      be given but solutions can be proposed. In high-grade gliomas, results of 3D
      conformal irradiation are fair. Stereotactic irradiation produces more
      encouraging survival rates but the range of doses delivered is too large for
      allowing recommendations. However, fractions less than 5Gy seem better tolerated.
      In brain metastases, total brain irradiation seems useful if metastases are
      multiple and the patient in good condition. With radiosurgery, local control
      rates are high and survival encouraging. In a retrospective study, bifractionated
      irradiation looked interesting when compared to radiosurgery. Overall prospective
      trials seem to be necessary.

PMID- 20797889
TI  - [Benefit of intensity modulated and image-guided radiotherapy in prostate
      cancer].
AB  - External beam radiotherapy (RT) is used to treat all stages of localized prostate
      cancer. Using a 3D conformal RT (3DCRT) without any androgen deprivation, a clear
      dose-effect relationship has been shown in terms of both biochemical control and
      also unfortunately of rectal and urinary toxicity. Compared to a "standard"
      3DCRT, intensity modulated RT (IMRT) improves the dose distribution by mainly
      providing concave dose distribution and tight dose gradients. Based on large
      clinical experiences for at least one decade, IMRT is widely used to increase the
      dose in the prostate and therefore local control, without increasing toxicity.
      Indeed, toxicity rates observed after high dose delivered in the prostate (80Gy)
      with IMRT appear no different than those observed after a standard dose (70Gy)
      delivered by a standard 3DCRT. Arc IMRT appears a new promising IMRT modality,
      decreasing dramatically treatment duration. However, this IMRT-based dosimetric
      benefit may not be translated into a full clinical benefit, if intra-pelvic
      prostate motion is not taken in account. Image-guided radiotherapy (IGRT) should
      be therefore associated with IMRT for a maximal clinical benefit. This article is
      a literature review showing the interest of both combined approaches.

PMID- 20797890
TI  - [Dosimetric factors predictive of late toxicity in prostate cancer radiotherapy].
AB  - Dose escalation in prostate cancer is made possible due to technological advances
      and to precise dose-volume constraints to limit normal tissue damage. This
      article is a literature review focusing on the correlations between exposure
      (doses and volumes) of organs at risk (OAR) and rectal, urinary, sexual and bone
      toxicity, as well as on mathematical models aiming at toxicity prediction. Dose
      volume constraint recommendations are presented that have been shown to be
      associated with reduced rectal damage. Indeed, the clinical data is relatively
      strong for late rectal toxicity (bleeding), with constraints put on both the
      volume of the rectum receiving high doses (>=70 Gy) and the volume receiving
      intermediate doses (40 to 60 Gy). Predictive models of rectal toxicity (Normal
      Tissue Complication Probability) appear to accurately estimate toxicity risks.
      The correlations are much weaker for the bulb and the femoral heads, and nearly
      do not exist for the bladder. Further prospective studies are required, ideally
      taking into account patient-related risk factors (co-morbidities and their
      specific treatments), assays of normal tissue hypersensitivity to ionizing
      radiation and mathematical models applied on 3D images acquired under the
      treatment machine (e.g. Cone Beam CT).

PMID- 20797891
TI  - Long-term quality of life in patients with rectal cancer treated with
      preoperative (chemo)-radiotherapy within a randomized trial.
AB  - PURPOSE: Few studies have evaluated the quality of life (QoL) of patients with
      rectal cancer. This report describes the quality of life of French patients who
      entered the 22921 EORTC trial that investigated the role and place of
      chemotherapy (CT) added to preoperative radiotherapy (preop-RT). PATIENTS AND
      METHODS: Patients without recurrences were evaluated with EORTC QLQ-C30 and QLQ
      CR38 questionnaires, after a median time of 4.6 years from randomisation.
      RESULTS: All the scores of QLQ-C30 functions were high, from 78 up to 88, with
      those of global health quality of life scale (GHQL) status being 73. The mean
      scores of symptoms were low except for diarrhoea. For QLQ-CR38, the mean scores
      for "body image" and "future perspective" were high at 79.6 and 69.7
      respectively. The scores for "sexual functioning" and "enjoyment" were low. Men
      had more sexual problems than females (62.5 vs 25 mean scores respectively).
      Chemotherapy was associated with more diarrhoea complaints, lower "role", lower
      "social functioning" and lower global health quality of life scale. CONCLUSION:
      The overall quality of life of patients with rectal cancer is quite good 4.6
      years after the beginning preoperative treatments. However, adding chemotherapy
      to preoperative radiotherapy has a negative effect on diarrhoea complaints and
      some quality of life dimensions.

PMID- 20797892
TI  - [What is new in the local approach of limb sarcomas and desmoid tumours?].
AB  - The treatment of soft tissue sarcomas of limbs should be discussed within an
      experienced multimodality team. Surgical resection remains the cornerstone of
      therapy for localized disease and achieves a five years overall survival around
      75% and a local recurrence rate as low as 10% in the best series. In complex
      cases, neo-adjuvant treatments may be used such as systemic chemotherapy,
      isolated limb perfusion, or radiotherapy to achieve an optimal conservative
      approach. Molecular genetics of sarcomas and quality of margins are essential to
      guide diagnosis and therapeutic selection. In case of marginal or incomplete
      resection, a new enlarged surgical resection should always be discussed before
      administration of any adjuvant treatments. Many retrospective studies and two
      randomized studies (one of adjuvant brachytherapy and one of external beam
      radiotherapy) have shown that adjuvant radiotherapy after complete surgery
      significantly reduces the risk of local recurrence in extremity soft tissue
      sarcomas. A randomized study has compared pre- to postoperative radiotherapy. The
      results in terms of local control are similar in both arms. The risk of surgical
      complications is higher in the preoperative arm and the risk of late sequelae is
      higher in the postoperative arm. A randomized study within the French sarcoma
      group is ongoing evaluating the omission of postoperative radiotherapy in
      favourable cases. Presently, the role of systematic first-line invasive treatment
      (including surgery and/or radiotherapy) of desmoids is debated. It is becoming
      evident that up to 50% of patients with desmoids benefit from a front-line non
      aggressive policy, because growth arrest is a common feature of this disease.
      Additional study of the molecular determinants of desmoid behaviour is needed to
      guide treatment.

PMID- 20797893
TI  - Convenient ultrasound-mediated synthesis of 1,4-diazabutadienes under solvent
      free conditions.
AB  - An ultrasound-assisted preparation of 1,4-diazabutadienes via smooth condensation
      of diketones with amines under solvent-free conditions is described. The
      generality of this method was examined by the synthesized N,N'-diaryl- and N,N'
      dialkyl-1,4-diazabutadiene derivatives. In addition to experimental simplicity,
      the main advantages of the procedure are mild conditions, short reaction time (2
      15 min) and high yields (71-98%).

PMID- 20797894
TI  - Optimization of ultrasound-accelerated synthesis of enzymatic caffeic acid
      phenethyl ester by response surface methodology.
AB  - The ultrasound-accelerated enzymatic synthesis of caffeic acid phenethyl ester
      (CAPE) from caffeic acid and phenethyl alcohol was investigated in this study. A
      commercial immobilized lipase from Candida antarctica, called Novozym(r) 435, was
      used as the catalyst. A 5-level-4-factor central-composite rotatable design
      (CCRD) and response surface methodology (RSM) were employed to evaluate the
      effects of reaction time, substrate molar ratio, enzyme amount, and ultrasonic
      power on percent molar conversion of CAPE. The results indicated that reaction
      time, substrate molar ratio, and ultrasonic power significantly affected percent
      molar conversion, whereas enzyme amount did not. A model for synthesis of CAPE
      was established. Based on ridge max analysis, the optimum condition for CAPE
      synthesis was predicted to be reaction time 9.6 h, substrate molar ratio 1:71,
      enzyme amount 2938 PLU, and ultrasonic power 2 W/cm(2) with the molar conversion
      value of 96.03 +/- 5.18%. An experiment was performed under this optimal
      condition and molar conversion of 93.08 +/- 0.42% was obtained.

PMID- 20797895
TI  - Ionic liquid under ultrasonic irradiation towards a facile synthesis of
      pyrazolone derivatives.
AB  - Ionic liquid [HMIM]HSO(4) was found to be an efficient catalyst for the synthesis
      of 4-[(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-phenyl-methyl]-5-methyl-2
      phen-yl-1,2-dihydro-pyrazol-3-ones through the condensation reaction of
      arylaldehydes and 3-methyl-1-phenyl-5-pyrazolone under ultrasonic irradiation at
      room temperature. The present methodology offers several advantages such as
      excellent yields, simple procedure and mild conditions.

PMID- 20797896
TI  - Effects of sonochemical parameters and inorganic ions during the sonochemical
      degradation of crystal violet in water.
AB  - This work deals with the ultrasonic degradation (800 kHz) of crystal violet (CV)
      under different experimental conditions. The effects of saturating gas (argon,
      carbon dioxide and air), CV concentration (2.45-1225 MUmol L(-1)), pH (3-9) and
      power (20-80 W) were evaluated. The best performances were obtained at 80 W with
      argon as a saturating gas. The pH had no significant effect. The influence of
      several water matrices containing anions (chloride, sulphate and bicarbonate) and
      cations (Fe(2+)) on the sonolytic degradation of CV was also investigated.
      Significant differences were not observed with the presence of chloride and
      sulphate. However, at relatively low pollutant concentration (2.45 MUmol L(-1))
      bicarbonate showed a particular effect: a high bicarbonate concentration (350
      mmol L(-1)) produced a detrimental effect, while a low bicarbonate concentration
      (3 mmol L(-1)) increased the efficiency of the process. The presence of Fe(2+) (1
      mmol L(-1)) also increased the CV (49 MUmol L(-1)) degradation by 32% after 180
      min. Analyses of intermediates by GC-MS led to the identification of several
      sonochemical by-products: N,N-dimethylaminobenzene, 4-(N,N-dimethylamino)-4'
      (N',N'-dimethylamino)benzophenone, and N,N,N',N'-tetramethyl-4,4'
      diaminodiphenylmethane. The presence of these aromatic structures showed that the
      main ultrasonic CV degradation pathway is linked to the reaction with *OH
      radicals. At the end of the treatment, these early products were converted into
      biodegradable organic by-products which could be easily treated in a subsequent
      biological treatment.

PMID- 20797898
TI  - Mortality-temperature thresholds for ten major population centres in rural
      Victoria, Australia.
AB  - Mortality-temperature relationships in small regional towns in Victoria,
      Australia, were used to ascertain whether the effects of high ambient
      temperatures documented in the literature for major population centres in Europe
      and America are also noted in small rural communities in Australia. The
      establishment of threshold temperatures in all major rural regions of Victoria
      indicate that hot weather results in an increase in mortality in persons aged 65
      years and older. This adds considerable strength to the argument that human
      populations are vulnerable to heat events regardless of location. Heat alerts can
      be issued through local health and welfare agencies, to increase awareness of
      'hot' weather as a health hazard for elderly people by providing education
      campaigns involving local authorities based on these simple thresholds.

PMID- 20797897
TI  - Using Google Earth to conduct a neighborhood audit: reliability of a virtual
      audit instrument.
AB  - Over the last two decades, the impact of community characteristics on the
      physical and mental health of residents has emerged as an important frontier of
      research in population health and health disparities. However, the development
      and evaluation of measures to capture community characteristics is still at a
      relatively early stage. The purpose of this work was to assess the reliability of
      a neighborhood audit instrument administered in the city of Chicago using Google
      Street View by comparing these "virtual" data to those obtained from an identical
      instrument administered "in-person". We find that a virtual audit instrument can
      provide reliable indicators of recreational facilities, the local food
      environment, and general land use. However, caution should be exercised when
      trying to gather more finely detailed observations. Using the internet to conduct
      a neighborhood audit has the potential to significantly reduce the costs of
      collecting data objectively and unobtrusively.

PMID- 20797899
TI  - Recurrence rate of keratocystic odontogenic tumor after conservative surgical
      treatment without adjunctive therapies - A 35-year single institution experience.
AB  - The recurrence rate in conservative surgical treatment, without adjunctive
      treatment, of the keratocystic odontogenic tumor (KCOT) has been studied. A total
      number of 68 patients, previously untreated and fulfilling the histopathological
      criteria provided by the 2005 WHO classification, has been retrospectively
      reviewed. The study period lasted from 1975 to 2009. Treatment consisted of
      enucleation (n=58) or marsupialization (n=10). The mean follow-up period was 65
      months. No involved or adjacent teeth were removed, except for wisdom teeth, if
      applicable, and badly decayed teeth. After enucleation, the recurrence rate was
      20.7% in a mean follow-up period of 46 months, while 40% of the marsupialized
      KCOTs recurred in a mean follow-up period of 58 months. In none of the patients
      permanent loss of nerve function has been observed. Due to the recurrence rate
      observed in the present study, and in view of the potential benefit of adjunctive
      treatment in KCOT, particularly with regard to the use of Carnoy's solution,
      there is a need for prospective studies to test its usefulness with regard to the
      risk of recurrences.

PMID- 20797900
TI  - Neurophysiological evaluation of motor corticospinal pathways by TMS in
      idiopathic early-onset Parkinson's disease.
AB  - OBJECTIVE: In a previous study we found altered motor corticospinal conduction in
      patients with early-onset Parkinson's disease (EOPD) and parkin gene mutations
      (PARK2). Aim of the present study was to evaluate central motor conduction in
      patients with EOPD, negative for parkin mutations to establish if prolonged CMCT
      is specific of PARK2 or it may be present in other EOPD patients. METHODS: Eleven
      patients with non-PARK2 EOPD underwent transcranial magnetic stimulation (TMS) to
      evaluate central motor conduction time (CMCT). Motor threshold (MT), motor evoked
      potential (MEP) amplitude, central silent period threshold (cSPT), and duration
      were also determined. RESULTS: All patients but one showed normal CMCT. CMCT and
      the other electrophysiological data did not differ significantly between patients
      and healthy controls, except for cSPT mean value which was higher in patients
      than in controls (p=0.008). No significant correlation was found between
      electrophysiological and clinical data in EOPD patients. CMCT was significantly
      prolonged in six PARK2 patients compared to non-PARK2 patients. CONCLUSIONS: We
      conclude that CMCT is usually normal in idiopathic EOPD: we suggest that in
      presence of a prolonged CMCT the diagnosis of PARK2 should be considered.
      SIGNIFICANCE: CMCT may represent a simple electrophysiological test that could be
      utilized in an early phase of diagnosis to differentiate PARK2 patients from
      those with idiopathic EOPD.

PMID- 20797901
TI  - Follicular-fluid anti-Mullerian hormone concentration is similar in patients with
      endometriosis compared with non-endometriotic patients.
AB  - This cross-sectional prospective study assessed follicular-fluid anti-Mullerian
      hormone (AMH) concentrations in infertile patients with mild/minimal
      endometriosis during natural IVF. Thirty-two women participated in the study.
      Patients were divided into two groups: tubal obstruction without endometriosis
      (control group) and minimal/mild endometriosis (study group). All patients
      underwent laparoscopy for assessment of infertility; at the same time, any foci
      of endometriosis found were cauterized. AMH concentration was measured in the
      follicular fluid of a single follicle when it achieved pre-ovulatory maturation
      by ultrasensitive enzyme-linked immunosorbent assay. Likewise, AMH, FSH and
      inhibin B content in serum was also measured. Age (30 +/- 1.3 and 32 +/- 0.8
      years) and body mass index (22 +/- 0.6 and 22 +/- 0.5 kg/m(2)), day-3 antral
      follicle count (11.3 +/- 1.7 and 10.7 +/- 1.5), serum FSH concentrations (5.4 +/-
      0.6 and 5.0 +/- 0.3 IU/ml) and follicular-fluid AMH concentrations (1.8 +/- 0.3
      and 1.5 +/- 0.1 ng/ml, study and control group, respectively; mean difference
      0.33, 95% CI -0.21 to 0.88) were similar in both groups. This study shows that
      infertile patients with minimal/mild endometriosis have a similar concentration
      of AMH in the follicular fluid after natural IVF as compared with control
      subjects.

PMID- 20797902
TI  - Analysis of oocyte cryopreservation in assisted reproduction: the Italian
      National Register data from 2005 to 2007.
AB  - This paper reports on oocyte cryopreservation efficacy in Italy with respect to
      successful IVF from 2005 to 2007, presenting data from 193 centres collected by
      the Italian National Register. Post-thawing survival rates, number of transferred
      embryos, implantation rates and clinical pregnancy rates per transfer with
      respect to frozen/vitrified oocytes (FVO) were analysed. These numbers were
      compared with those obtained using frozen embryos or fresh oocytes. A total of
      121,708 cycles were initiated, of which, 7.1% (8682) were FVO cycles and 2.4%
      (2952) were frozen embryo cycles. Of the 81,786 FVO, 52.5% (42,917) were thawed
      and 26.9% (22,005) inseminated. Of those inseminated, 68.0% (14,966) yielded good
      embryos. These numbers were significantly lower than those using fresh oocytes in
      which 77.9% (197,242; fresh oocytes versus FVO P<0.001) of inseminated oocytes
      generated good embryos. Implantation rate using FVO was 6.9%, which was
      significantly lower than that using fresh oocytes (13.5%; P<0.001) and frozen
      embryos (8.8%; P<0.001). Pregnancy rate per transfer using FVO was 12.5% and
      significantly lower than that using fresh oocytes (24.9%; P<0.001) or frozen
      embryos (16.4%; P<0.001). There were 505 deliveries after IVF with FVO and 582
      babies.

PMID- 20797903
TI  - Normal serum concentrations of anti-Mullerian hormone in women with regular
      menstrual cycles.
AB  - Anti-Mullerian hormone (AMH) has become the 'molecule of the moment' in the field
      of reproductive endocrinology. Indeed, it is valuable as a means of increasing
      understanding of ovarian pathophysiology and for guiding clinical management
      across a broad range of conditions. However, no normative values have been
      established for circulating AMH in healthy women. In this cross-sectional study,
      277 healthy females (aged 18-50 years) were included. AMH was measured by
      commercial enzyme-linked immunosorbent assay. Serum AMH concentrations show a
      progressive decline with female ageing. The age-related changes in AMH were best
      fitted by a polynomial function. Mean AMH concentrations were not modified by
      past use of oral contraceptive and were independent of parity of women. Age
      specific normative values for circulating AMH concentration were established. AMH
      concentrations seem to be independent of the reproductive history of the patient.

PMID- 20797904
TI  - Blastocysts from patients with polycystic ovaries exhibit altered transcriptome
      and secretome.
AB  - Polycystic ovaries (PCO) is a common phenotype of women presenting for
      infertility treatment. This study investigated whether blastocysts derived from
      women with PCO have an altered molecular signature which could be a causative
      factor contributing to reproductive failure. Morphologically similar blastocysts
      derived from women with PCO and donor oocyte cycles were analysed for
      transcription and protein secretion. Unsupervised hierarchical clustering
      demonstrated that the transcriptome profiles of blastocysts derived from PCO
      patients and control blastocysts were markedly different with complete branch
      separation. Statistical analysis revealed 829 genes with significantly different
      expression: 784 decreased (94.6%) and 45 increased (5.4%) in blastocysts derived
      from women with PCO compared with controls (P<0.05). Functional annotation of
      these genes revealed predominant gene ontology biological processes including
      protein metabolism (30%), transcription (22%), signal transduction (15%),
      biosynthesis (15%) and cell cycle (14%). Proteomic profiling identified 12
      biomarkers that displayed significant decrease in expression in blastocysts
      derived from women with PCO compared with controls (P<0.05). These data indicate
      molecular alterations in human blastocysts derived from PCO patients, potentially
      demonstrating for the first time a link between patient aetiology/phenotype and
      subsequent embryo development, which in part may explain the observed reduction
      in reproductive capacity.

PMID- 20797905
TI  - Toll-like receptor and TIRAP gene polymorphisms in pulmonary tuberculosis
      patients of South India.
AB  - Toll-like receptors (TLRs) are pattern recognition receptors and play an
      important role in innate immunity. Changes in TLRs and signaling molecules that
      result from polymorphisms are often associated with susceptibility to various
      infectious diseases. In the present study, we investigated whether variants in
      the TLR-1 1805T/G (Ile602Ser), TLR-2 2258G/A (Arg753Gln), TLR-4 896A/G
      (Asp299Gly), TLR-4 1196C/T (Thr399Ile), TLR-6 745C/T (Ser249Pro), TIRAP 975C/T
      (Ser180Leu) genes and TLR-9 promoter region polymorphisms at positions -1237C/T
      and -1486C/T are associated with susceptibility or resistance to pulmonary
      tuberculosis (PTB). Genotyping of TLR and TIRAP gene polymorphisms was performed
      by polymerase chain reaction followed by restriction fragment length polymorphism
      method in 212 healthy control subjects (HCs) and 206 PTB patients. The allele and
      genotype frequencies of various TLR genes were not different between the HCs and
      PTB patients. However, the study is underpowered to detect minor associations.
      The frequency of T allele of TIRAP 975C/T (Ser180Leu) polymorphism was
      significantly increased among PTB patients as compared to HCs [p = 0.026; Odds
      ratio (OR) 1.49, 95% Confidence interval (CI) 1.049-2.22]. A trend towards an
      increased frequency of TT genotype of TIRAP 975C/T was also observed in PTB
      patients [p = 0.078, OR 3.10 95% CI (0.96-10.05)]. The present study suggests
      that T allele of TIRAP 975C/T polymorphism may be associated with susceptibility
      to pulmonary TB in south Indian population. Further study on the regulatory role
      of this polymorphism may be helpful to understand the innate immunity in TB.

PMID- 20797907
TI  - Use of qualitative research to inform development of nutrition messages for low
      income mothers of preschool children.
AB  - OBJECTIVE: To develop and test nutrition messages and supporting content with low
      income mothers for use with theory-based interventions addressing fruit and
      vegetable consumption and child-feeding practices. DESIGN: Six formative and 6
      evaluative focus groups explored message concepts and tested messages,
      respectively. SETTING: Research facilities in Maryland, Texas, California,
      Florida, North Carolina, New York, Alabama, and Illinois. PARTICIPANTS: Ninety
      five low-income mothers of 2- to 5-year-old children; over half from households
      participating in a federal nutrition assistance program. PHENOMENON OF INTEREST:
      Preference for and comprehension of nutrition messages. ANALYSIS: Qualitative
      data analysis procedures to generate common themes from transcripts and
      observers' notes. RESULTS: Messages on role modeling, cooking and eating
      together, having patience when introducing new food items, and allowing children
      to serve themselves were well received. Mothers preferred messages that
      emphasized their role as a teacher and noted benefits such as their children
      becoming more independent and learning new skills. Mothers commonly doubted
      children's ability to accurately report when they are "full" and disliked
      messages encouraging mothers to allow children to "decide" whether and how much
      to eat. CONCLUSIONS AND IMPLICATIONS: This study generated 7 audience-tested
      messages for incorporation into nutrition education interventions targeting low
      income mothers of preschool-age children.

PMID- 20797908
TI  - T cell vaccination therapy in an induced model of anti-RNP autoimmune
      glomerulonephritis.
AB  - To establish the relevance of targeting disease-associated T cells in anti-RNP
      associated glomerulonephritis, mice developing nephritis following immunization
      with U1-70-kd small nuclear ribonucleoprotein (snRNP) were treated with a single
      dose of irradiated antigen-selected T cell vaccine. T cell receptor usage in
      nephritic kidneys revealed oligoclonal use of T Cell Receptor V Beta (TRBV) genes
      as previously found in spleens and lungs of immunized mice with pulmonary
      disease. The CDR3 regions from T cell isolates showed sequence homology to those
      in humans with anti-RNP autoimmunity. Following T cell vaccination, urinalysis
      returned to normal in 5/7 treated mice (71% response rate) whereas all mock
      treated mice continued to have an active urinary sediment (Fisher's Exact
      p=0.02). An oligoclonal population of T cells homologous to those identified in
      humans with anti-RNP autoimmunity is implicated in disease pathogenesis, and T
      cell vaccination is associated with a high rate of clinical improvement in
      established nephritis.

PMID- 20797909
TI  - Susceptibility to pulmonary disease due to Mycobacterium avium-intracellulare
      complex may reflect low IL-17 and high IL-10 responses rather than Th1
      deficiency.
AB  - It remains unclear why some individuals and not others are susceptible to non
      tuberculous mycobacterial lung disease (NTMLD). To determine whether NTMLD is
      associated with defects or biases in Th1/Th2/Th17 immunity, blood leukocytes from
      NTM patients with nodular bronchiectasis, their adult offspring, and healthy
      population controls were stimulated with staphylococcal enterotoxin B (SEB),
      tuberculin and sensitin to measure cytokine production. In response to SEB, NTM
      patients exhibited higher frequencies of IFNgamma-producing CD4(+) T cells than
      population controls (P<0.001). In supernatant, levels of IL-17 were lower in
      patients than adult offspring. Sensitin elicited higher IFNgamma responses from
      patients than controls (P<0.05). Patients also produced more IL-10 in supernatant
      than controls after culture with tuberculin (P<0.01) or sensitin (P<0.05), but IL
      10-producing CD4(+) T cells were undetectable. NTMLD is not associated with
      deficient IFNgamma production, but may be associated with reduced Th17 immunity
      and/or a predisposition towards IL-10 production from non-CD4(+) T cells.

PMID- 20797910
TI  - Nrf2 is closely related to allergic airway inflammatory responses induced by low
      dose diesel exhaust particles in mice.
AB  - We have recently reported that disruption of nuclear erythroid 2 P45-related
      factor 2 (Nrf2) enhances susceptibility to airway inflammatory responses induced
      by low-dose diesel exhaust particles (DEP) in mice. C57BL/6 Nrf2 knockout (Nrf2(
      /-)) mice and wild-type (Nrf2(+/+)) mice were further exposed to low-dose DEP for
      7h/day, 5 days/week, for a maximum of 8 weeks. After exposure to DEP for 5 weeks,
      allergic airway inflammation was generated in the mice by intraperitoneal
      sensitization with OVA followed by intranasal challenge. Nrf2(-/-) mice exposed
      to relatively low-dose DEP showed significantly increased percentage changes
      relative to the OVA alone group in terms of airway hyperresponsiveness (AHR) and
      inflammatory cells, levels of IL-5 and thymus and activation regulated chemokine
      (TARC) in bronchoalveolar lavage (BAL) fluid than did Nrf2(+/+) mice. Lung
      tissues of Nrf2(-/-) mice after DEP exposure showed inflammatory cell
      infiltrates, and increased PAS staining-positive mucus cell hyperplasia. In
      contrast, the percentage changes relative to the OVA group in the reduced
      glutathione (GSH)/oxidized glutathione (GSSG) ratio in whole blood was higher in
      Nrf2(+/+) mice than in Nrf2(-/-) mice. By using Nrf2(-/-) mice, it was shown for
      the first time that relatively low-dose DEP exposure induces oxidant stress, and
      that host anti-oxidant responses play a key role in the development of DEP
      induced exacerbation of allergic airway inflammation.

PMID- 20797911
TI  - Involvement of brain-derived neurotrophic factor (BDNF) in MP4-induced autoimmune
      encephalomyelitis.
AB  - The role of brain-derived neurotrophic factor (BDNF) in multiple sclerosis and
      experimental autoimmune encephalomyelitis (EAE) is still unclear. Here we
      investigate the clinical course, CNS histopathology and peripheral antigen
      specific immunity in MP4-induced EAE of BDNF (-/+) mice. We demonstrate that
      these mice displayed less severe disease compared to BDNF (+/+) mice, reflected
      by decreased inflammation and demyelination. In correspondence to diminished
      frequencies of T and B cells in CNS infiltrates, the peripheral MP4-specific
      T(H)1/T(H)17 response was attenuated in BDNF (-/+), but not in wild-type animals.
      In contrast, immunization with ovalbumin triggered similar frequencies of IFN
      gamma- and IL-17-secreting T cells in both groups. The cytokine secretion and
      proliferative activity upon mitogen stimulation did not reveal any global defect
      of T cell function in BDNF (-/+) mice. By influencing the antigen-specific immune
      response in autoimmune encephalomyelitis, BDNF may support and maintain the
      disease in ways that go beyond its alleged neuroprotective role.

PMID- 20797912
TI  - Cortical language mapping using electrical cortical stimulation for Mandarin
      speaking patients with epilepsy: a report of six case studies.
AB  - OBJECTIVE: The goal of this study was to summarize the results of language cortex
      mapping using electrical cortical stimulation with modified language tasks for
      Mandarin-speaking patients with epilepsy. METHODS: Electrical currents were
      delivered through implanted subdural electrodes to six Mandarin-speaking patients
      before epilepsy surgery. The current intensities inducing any language
      disturbance during comprehension, repetition, and speech tasks were recorded, and
      individual cortical mapping was completed to guide subsequent resection, with the
      distance between mapped language sites and resected zones kept at a minimum of
      0.5 cm. Language function was reassessed and followed up after surgery. RESULTS:
      Language cortices were successfully identified in three patients, but
      demonstrated great variability in distribution. There seemed to be no difference
      in the intensity threshold that induced language interference. None of the six
      patients exhibited language deficits postsurgery. CONCLUSIONS: Electrical
      cortical stimulation with modified language tasks is valid for identification of
      cortices underlying Mandarin processing. The great variability in language cortex
      distribution enhances the necessity of individual language cortical mapping in
      epilepsy surgery.

PMID- 20797913
TI  - Benign epilepsy of childhood with centrotemporal spikes (BECTS): to treat or not
      to treat, that is the question.
AB  - The goal of this review is to assess the value of treating versus not treating
      benign epilepsy (of childhood) with centrotemporal spikes (BECTS). Among 110
      recommendations from 96 articles, two-thirds generally favored and one-third
      generally did not favor treatment with antiepileptic drugs (AEDs). Two studies
      concluded that all patients should be treated, but most investigators added
      qualifications, for example, treating those with early onset, multiple seizures
      at onset, and large numbers of seizures, especially generalized tonic-clonic
      seizures, and limiting treatment to 1 year. Other studies made treatment
      dependent on epileptiform discharges or amelioration of symptoms. Specific AEDs
      were reviewed, and in the largest number of positive studies, valproic acid or
      carbamazepine was favored. Among the studies generally opposing treatment, none
      opposed treatment for all patients in all circumstances. Usually, qualifications
      to treat were added, for example, if generalized tonic-clonic seizures occurred
      or if there was a change in quality of life. One AED associated with negative
      effects was carbamazepine, treatment with which can result in the development of
      epileptic negative myoclonus, absence seizures, and generalized spike-wave
      complexes on the EEG. Thus, if treatment is planned, valproic acid may be
      considered the drug of choice in BECTS. Although many neurologists oppose
      treatment; twice as many studies concluded in favor of treatment. The typical
      benign aspect of this disorder may allow for nontreatment to be without serious
      consequences.

PMID- 20797914
TI  - Attention networks in children with idiopathic generalized epilepsy.
AB  - Attention deficit is one of the most frequent symptoms in children with
      idiopathic generalized epilepsy (IGE). However, it is unknown whether this is a
      global attention deficit or a deficit in a specific attention network. We used
      the attention network test (ANT) in children with IGE, who were not being treated
      with antiepileptic drugs (AEDs), to determine the efficiencies of three
      independent attention networks (alerting, orienting, and executive control).
      Children with IGE showed a significant deficit in their executive control network
      and in overall reaction time. However, they did not show any deficit in their
      alerting or orienting networks. These results suggest that IGE specifically
      affects the executive control network.

PMID- 20797915
TI  - Documentation of autonomic seizures and autonomic status epilepticus with ictal
      EEG in Panayiotopoulos syndrome.
AB  - Panayiotopoulos syndrome (PS) is a common childhood susceptibility to autonomic
      seizures and status epilepticus. Despite its high prevalence, PS has been a
      source of significant debate. We present ictal EEG documentation of autonomic
      seizures and autonomic status epilepticus in six cases of PS and a review of 14
      reported cases. Interictal EEGs showed spikes of variable locations that often
      changed with time. Ictal EEG onsets were also variable, starting from wide
      anterior or posterior regions usually with theta waves intermixed with small
      spikes and fast rhythms. Ictal vomiting and other autonomic manifestations, as
      well as deviation of the eyes, did not appear to relate to any specific region of
      EEG activation. These data document that PS is a multifocal autonomic epilepsy
      and support the view that the clinical manifestations are likely to be generated
      by variable and widely spread epileptogenic foci acting on a temporarily
      hyperexcitable central autonomic network.

PMID- 20797916
TI  - The prevalence of chronic pain in United States adults: results of an Internet
      based survey.
AB  - A cross-sectional, Internet-based survey was conducted in a nationally
      representative sample of United States (US) adults to estimate the point
      prevalence of chronic pain and to describe sociodemographic correlates and
      characteristics of chronic pain. The survey was distributed to 35,718 members
      (aged 18 years and older) of a Web-enabled panel that is representative of the US
      population, and 27,035 individuals responded. Crude and weighted prevalence
      estimates were calculated and stratified by age, sex, and type of chronic pain.
      The weighted point-prevalence of chronic pain (defined as chronic, recurrent, or
      long-lasting pain lasting for at least 6 months) was 30.7% (95% CI, 29.8-31.7).
      Prevalence was higher for females (34.3%) than males (26.7%) and increased with
      age. The weighted prevalence of primary chronic lower back pain was 8.1% and
      primary osteoarthritis pain was 3.9%. Half of respondents with chronic pain
      experienced daily pain, and average (past 3 months) pain intensity was severe (>=
      7 on a scale ranging from 0 to 10) for 32%. Multiple logistic regression analysis
      identified low household income and unemployment as significant socioeconomic
      correlates of chronic pain. Chronic pain is prevalent among US adults and is
      related to indicators of poorer socioeconomic status. PERSPECTIVE: The results of
      this cross-sectional Internet-based survey suggest a considerable burden of
      chronic pain in US adults. Chronic pain, experienced by about a third of the
      population, was correlated with indicators of poorer socioeconomic status.
      Primary chronic pain was most commonly attributed to lower back pain, followed by
      osteoarthritis pain.

PMID- 20797917
TI  - Topical application of compound Ibuprofen suppresses pain by inhibiting sensory
      neuron hyperexcitability and neuroinflammation in a rat model of intervertebral
      foramen inflammation.
AB  - There is lack of evidence that topical application of an anti-inflammatory
      reagent could reduce pain due to intervertebral foramen (IVF) inflammation
      (IVFI). We investigated analgesic effects and underlying mechanisms of topical
      application of a compound ibuprofen cream (CIC) onto the surface of back skin
      covering the inflamed L(5) IVF in a rat model. Repetitive CIC treatment (~.54 g
      each treatment daily for 5 consecutive days) significantly reduces severity and
      duration of IVFI-induced thermal hyperalgesia and mechanical allodynia by 80 to
      100% and 50 to 66%, respectively. Electrophysiological studies and Western blot
      analysis demonstrated that CIC treatment significantly inhibited
      hyperexcitability of the inflamed dorsal root ganglion (DRG) neurons and
      upregulation of Nav1.7 and Nav1.8 protein, respectively. Pathological
      manifestations of the inflamed DRG were also markedly improved following CIC
      treatment. Further, in the inflamed DRGs, phosphorylation and expression of
      transcription factor NF-kappaB and pro-inflammatory enzyme cyclooxygenase-2 (COX
      2) were significantly increased, while a cytokine IL-1beta level was increased.
      IVFI-induced upregulation of these molecules was significantly inhibited by CIC
      treatment. This study provides evidence that an anti-inflammatory reagent can be
      used topically to suppress pain due to IVFI and/or DRG inflammation through
      inhibition of sensory neuron hyperexcitability and the immune and inflammatory
      responses. PERSPECTIVE: This study suggests a convenient and safe clinical
      intervention for treating pain due to intervertebral foramen inflammation and
      similar syndromes.

PMID- 20797918
TI  - Attentional biases toward sensory pain words in acute and chronic pain patients.
AB  - Attentional biases towards pain-related words of chronic and acute low back pain
      (LBP) patients were compared with healthy pain-free controls. Specifically, the
      aims were to determine: 1) whether chronic LBP patients demonstrate attentional
      biases compared to pain-free controls; 2) whether observed biases are also
      present in those with acute LBP; and 3) whether observed biases are associated
      with pain-related fear among the pain groups. Four groups were recruited: 1)
      acute LBP patients; 2) chronic LBP patients from physiotherapy practices; 3)
      chronic LBP patients from a tertiary referral pain-management center; and 4)
      healthy pain-free controls. Participants were assessed on the dot-probe computer
      task for attentional bias to pain-related words. All 3 pain groups demonstrated
      biases compared to controls on sensory but not on affective, disability, or
      threat words. Among the pain groups, those with low and moderate levels of fear
      of (re)injury demonstrated biases towards sensory pain words that were absent in
      those with high levels of fear, which is counterintuitive to what the fear of
      (re)injury model suggests. These results suggest that the experience of pain,
      rather than duration, is the primary indicator of the presence of pain-related
      biases. PERSPECTIVE: Attentional biases are present in chronic and acute pain.
      Biases towards sensory-pain stimuli were demonstrated regardless of pain
      duration; however, they were present in those with low and moderate levels of
      fear of (re)injury only and not those high in fear. These findings are not
      consistent with the fear of (re)injury model.

PMID- 20797919
TI  - Median nerve small- and large-fiber damage in carpal tunnel syndrome: a
      quantitative sensory testing study.
AB  - We explored the contribution of median nerve small (Adelta, C)-and large (Abeta)
      fiber damage to the severity and topographic distribution of sensory symptoms in
      carpal tunnel syndrome (CTS) and the timing of fiber damage across CTS stages. We
      recruited 106 CTS patients. After selection, 49 patients were included. They
      underwent electrodiagnostic and quantitative sensory testing (QST) study and were
      asked on the severity of Boston Carpal Tunnel Questionnaire (BCTQ) Symptoms
      Severity Scale, daytime pain (DP), night pain and paresthesia, on the
      distribution of hand symptoms, and the presence of proximal symptoms. BCTQ
      Symptoms Severity Scale and DP severity was significantly correlated with Adelta
      fiber damage. Small-fiber QST measures were impaired in electrodiagnostic
      negative CTS patients and did not change across CTS neurographic stages. QST
      findings were not correlated to the topographical distribution of symptoms.
      Adelta-fiber damage contributes to CTS symptoms and in particular to DP. Night
      pain and paresthesia might be ascribed to ectopic fiber discharges secondary to
      median nerve enhanced mechanosensitivity. Small-fiber damage takes place earlier
      than large fiber. Median nerve fiber involvement does not directly contribute to
      extraterritorial symptoms spread. Our data may help understanding CTS
      pathophysiology and explain the well-known discrepancy between CTS symptoms and
      electrodiagnostic findings. PERSPECTIVE: We explored the involvement of median
      nerve small and large fibers in carpal tunnel syndrome (CTS). We found a
      significant correlation between Adelta-fiber function and CTS symptoms. Small
      fiber involvement took place in milder disease stages. These findings could help
      reconcile the discrepancy between CTS symptoms and electrodiagnostic data.

PMID- 20797920
TI  - The influence of non-nociceptive factors on hot-plate latency in rats.
AB  - The hot plate is a widely used test to assess nociception. The effect of non
      nociceptive factors (weight, sex, activity, habituation, and repeated testing) on
      hot-plate latency was examined. Comparison of body weight and hot-plate latency
      revealed a small but significant inverse correlation (light rats had longer
      latencies). Habituating rats to the test room for 1 hour prior to testing did not
      decrease hot-plate latency except for female rats tested on days 2 to 4. Hot
      plate latency decreased with repeated daily testing, but this was not caused by a
      decrease in locomotor activity or learning to respond. Activity on the hot plate
      was consistent across all 4 trials, and prior exposure to a room-temperature
      plate caused a similar decrease in latency as rats tested repeatedly on the hot
      plate. Despite this decrease in baseline hot-plate latency, there was no
      difference in morphine antinociceptive potency. The present study shows that
      weight, habituation to the test room, and repeated testing can alter baseline hot
      plate latency, but these effects are small and have relatively little impact on
      morphine antinociception. PERSPECTIVE: This manuscript shows that non-nociceptive
      factors such as body weight, habituation, and repeated testing can alter hot
      plate latency, but these factors do not alter morphine potency. In sum, the hot
      plate test is an easy to use and reliable method to assess supraspinally
      organized nociceptive responses.

PMID- 20797921
TI  - Don Lawrence and the "k-capture" revolution.
AB  - PURPOSE: The practice of brachytherapy was in steep decline in the mid-20th
      century, largely because of safety issues. This article explores the innovations
      that revitalized brachytherapy with special attention to the introduction of low
      energy seeds for permanent implantation. METHODS AND MATERIALS: Literature
      review; interviews; and the memos, records, and correspondence of Donald C.
      Lawrence. RESULTS: Paul Harper first proposed the use of radionuclides that decay
      by k-capture in the 1950s. But it was the vision and tenacity of health physicist
      Donald Lawrence that led to the successful implementation of I-125 (in the 1960s)
      and Cs-131 (40 years later).

PMID- 20797922
TI  - Acute bowel morbidity after prostate brachytherapy with cesium-131.
AB  - PURPOSE: The present study evaluates the severity and time to resolution of bowel
      symptoms in men undergoing prostate brachytherapy (PB) with cesium-131 ((131)Cs).
      METHODS AND MATERIALS: A longitudinal, prospective study of patients who had
      undergone PB with (131)Cs at a single institution was performed. All patients
      were asked to complete the Expanded Prostate Cancer Index Composite
      preoperatively and at 2 weeks and 1, 3, and 6 months postoperatively. Outcomes
      were analyzed using descriptive statistics and Student's t test. RESULTS: The
      first 142 patients to have undergone PB with (131)Cs at our institution were
      included in the study. The mean Expanded Prostate Cancer Index Composite bowel
      summary score at baseline was 90.1+/-11.0 compared with 71.5+/-22.8 (p=0.000),
      70.1+/-20.7, 87.1+/-13.8 (p=0.01), and 90.7+/-9.2 (p=0.70) at 2 weeks and 1, 3,
      and 6 months postoperatively, respectively. CONCLUSIONS: In men undergoing PB as
      monotherapy with (131)Cs, bowel symptoms returned to baseline by 3 months after
      the procedure. For patients undergoing PB with (131)Cs as part of combination
      therapy, bowel symptoms return to their post-external beam radiotherapy, pre-PB
      baseline by 3 months after the procedure.

PMID- 20797923
TI  - Mutational spectrum of cystic fibrosis in the Lebanese population.
AB  - BACKGROUND: Cystic fibrosis (CF) is the most common autosomal recessive disease
      in Caucasians; it is however, considered to be rare in the Arab populations.
      Reports of the cystic fibrosis transmembrane regulator (CFTR) mutations from
      Arabs, especially from the Lebanese population, are limited. METHODS: Twenty-two
      unrelated Lebanese families, with at least one child with CF, were studied. DNA
      extracts from blood samples of patients and parents were screened for CFTR gene
      mutations. RESULTS: Eleven different mutations were identified. Of the 44 alleles
      studied, the most common mutations were: F508del (34%), N1303K (27%), W1282X
      (7%), and S4X (7%). Five mutations - not previously reported in the Lebanese
      population - were identified; these are: S549N, G542X, 2043delG, 4016insG, and
      R117H-7T. CONCLUSIONS: The most common CFTR mutations in addition to five
      mutations not previously described in the Lebanese population were identified.
      Identification of CFTR mutations in the Lebanese population is important for
      molecular investigations and genetic counseling.

PMID- 20797924
TI  - Complete mtDNA of Meretrix lusoria (Bivalvia: Veneridae) reveals the presence of
      an atp8 gene, length variation and heteroplasmy in the control region.
AB  - The complete nucleotide sequence of the mitochondrial genome of the clam Meretrix
      lusoria (Bivalvia: Veneridae) was determined. It comprises 20,268 base pairs (bp)
      and contains 13 protein-coding genes, including ATPase subunit 8 (atp8), two
      ribosomal RNAs, 22 transfer RNAs, and a non-coding control region. The atp8
      encodes a protein of 39 amino acids. All genes are encoded on the same strand. A
      putative control region (CR or D-loop) was identified in the major non-coding
      region (NCR) between the tRNA(Gly) and tRNA(Gln). A 1087 bp tandem repeat
      fragment was identified that comprises nearly 11 copies of a 101 bp motif and
      accounts for approximately 41% of the NCR. The 101 bp tandem repeat motif of the
      NCR can be folded into a stem-loop secondary structure. Samples of eight
      individuals from Hainan and Fujian provinces were collected and their NCR regions
      were successfully amplified and sequenced. The data revealed a highly polymorphic
      VNTR (variable number of tandem repeats) associated with high levels of
      heteroplasmy in the D-loop region. The size of the CR ranged from 1942 to 3354 bp
      depending upon the copy number of the repeat sequence.

PMID- 20797925
TI  - Bilobed mucosal flap for correction of secondary lip deformities following cleft
      lip surgery.
AB  - BACKGROUND: Upper lip whistling deformities, asymmetric upper lip thickness and
      insufficient vermilion tubercle often occur simultaneously in an affected
      individual. Unfortunately, these deformities cannot be corrected by a single
      conventional method. Here, we describe a new technique, using a vermilion-bilobed
      flap, to address the triplex of deformities simultaneously. METHODS: A total of
      30 A Thirty patients were included in this study. Their ages ranged from 10 to 35
      years. The flap consisted of two lobes: one lobe of the flap was located at the
      oral mucosa of the prolabium, which allowed for correction of the whistle
      deformity as well as augmentation of the vermilion tubercle; the other was
      located at the vermilion mucosa on the lateral side of the cleft, which
      effectively repaired oral mucosal defects. Quantitative measurements of the
      vermilion shape were performed before surgery and 6 months postoperatively.
      RESULTS: All patients healed well with no complications of the flaps.The gross
      appearance of the vermilion was significantly improved. Normal tubercles were
      restored and symmetric profiles of vermilion were achieved. All the patients were
      satisfied with their final appearance. CONCLUSIONS: The bilobed vermilion mucosal
      flap is a safe technique, easy to perform and effectively corrects the combined
      secondary deformities associated with cleft lip surgery.

PMID- 20797926
TI  - Propranolol as first-line treatment for rapidly proliferating infantile
      haemangiomas.
AB  - Infantile haemangioma is the commonest childhood tumour and approximately 10%
      requires treatment.(1,2) Recent reports have highlighted the impressive efficacy
      of propranolol in treating rapidly proliferating haemangioma. The aims of our
      study were to prospectively assess the efficacy of propranolol as a first line
      treatment for problematic haemangioma, and develop a treatment regime. 31
      consecutive patients with rapidly proliferating infantile haemangioma with
      functional impairment or cosmetic disfigurement were treated with propranolol as
      a first line treatment. All patients had cardiovascular pre-treatment work-up and
      commenced on propranolol at 3 mg/kg/day. A rapid halt in haemangioma
      proliferation was seen in 100% of patients and significant regression in 87% of
      patients. This treatment is well tolerated and has little side effects. Since
      this study, our unit has adopted the policy of using propranolol as a first line
      treatment for all problematic proliferative infantile haemangiomas.

PMID- 20797927
TI  - Reconstruction of scrotal and perineal defects in Fournier's gangrene.
AB  - BACKGROUND: Fournier's gangrene is an acute and potentially lethal necrotising
      fasciitis that involves the scrotum and perineum. This disease can result in the
      loss of skin and soft tissue. To repair the scrotal and perineal defects remains
      a surgical challenge. METHODS: Between January 2000 and December 2008, 50
      patients were admitted to our hospital with a diagnosis of Fournier's gangrene.
      We retrospectively reviewed 31 of the 44 surviving patients, who needed
      reconstructive procedures for coverage of scrotal and perineal soft-tissue
      defects. The choice of reconstructive procedure was based on the size, location,
      severity of the defects and the availability of local tissue. The patients' age,
      predisposing factors, defect size and location, reconstructive procedures and
      outcomes were reviewed. RESULTS: The mean age of the patients was 53.6 years
      (range, 20-84 years). The average size of the skin defect was 86 cm(2). A total
      of 12 patients were treated by scrotal advancement flap coverage, nine by split
      thickness skin graft, five by pudendal thigh flap, two by gracilis myocutaneous
      flap, one by gracilis muscle flap plus split-thickness skin graft and three by
      pedicle anterolateral thigh flap. The overall surgical complication rate was 16%.
      CONCLUSIONS: Early debridement and wound coverage in Fournier's gangrene are
      mandatory to allow patients to return to normal life. We set up a valuable
      reconstructive algorithm based on the characteristics of the defects and our 9
      years of experience, which adds to the versatility of the armamentarium of the
      reconstructive surgeon.

PMID- 20797928
TI  - The isolated sympathetic spinal cord: Cardiovascular and sudomotor assessment in
      spinal cord injury patients: A literature survey.
AB  - OBJECTIVES: To present a comprehensive approach to the assessment of the severity
      of the autonomic lesion in spinal cord injury (SCI) patients, with regard to the
      level of lesion. To discuss how to assess an isolated sympathetic spinal cord
      that has lost supraspinal control (sympathetically complete lesion). METHOD:
      PubMed was searched for articles related to cardiovascular (mainly cold pressor
      test, respiratory and postural challenges) and sudomotor (sympathetic skin
      responses) tests that have been used. The results of these evaluations are
      analysed with regard to the site of stimulation (above or below the lesion)
      according to three types of SCI that offer typical autonomic reactions
      (tetraplegics, paraplegics at T6 and at T10). RESULTS: Non-invasive
      cardiovascular and sudomotor testing allows the assessment of the isolated
      sympathetic spinal cord in SCI patients. Typical responses are found in relation
      with the level of the sympathetic lesion. Its definition would allow comparison
      with the somatic motor and sensory level of lesion of SCI patients and provide
      additional aid to the classification of those patients. CONCLUSION: For research
      purposes on the integrity of the spinal sympathetic pathways, a battery of test
      approach is probably needed, using a combination of stimuli above and below the
      lesion, evaluating both cardiovascular and sudomotor pathways.

PMID- 20797929
TI  - Daily bisphenol A excretion and associations with sex hormone concentrations:
      results from the InCHIANTI adult population study.
AB  - BACKGROUND: Bisphenol A (BPA) is a high production volume chemical widely used in
      packaging for food and beverages. Numerous studies have demonstrated that BPA can
      alter endocrine function in animals, yet human studies remain limited. OBJECTIVE:
      We estimated daily excretion of BPA among adults and examined hypothesized
      associations with serum estrogen and testosterone concentrations. METHODS: We
      conducted cross-sectional analyses using data from the InCHIANTI Study, a
      prospective population-based study of Italian adults. Our study included 715
      adults between 20 and 74 years old. BPA concentrations were measured by liquid
      chromatography-mass spectrometry in 24-hr urine samples. The main outcome
      measures were serum concentrations of total testosterone and 17beta-estradiol.
      RESULTS: Geometric mean urinary BPA concentration was 3.59 ng/mL [95% confidence
      interval (CI), 3.42-3.77 ng/mL], and mean excretion was 5.63 microg/day (5th
      population percentile, 2.1 microg/day; 95th percentile, 16.4 microg/day). We
      found higher excretion rates among men, younger respondents, and those with
      increasing waist circumference (p = 0.013) and weight (p = 0.003). Higher daily
      BPA excretion was associated with higher total testosterone concentrations in
      men, in models adjusted for age and study site (p = 0.044), and in models
      additionally adjusted for smoking, measures of obesity, and urinary creatinine
      concentrations (beta = 0.046; 95% CI, 0.015-0.076; p = 0.004). We found no
      associations with the other serum measures. We also found no associations with
      the primary outcomes among women, but we did find an association between BPA and
      SHBG concentrations in the 60 premenopausal women. CONCLUSION: Higher BPA
      exposure may be associated with endocrine changes in men. The mechanisms involved
      in the observed cross-sectional association with total testosterone
      concentrations need to be clarified.

PMID- 20797930
TI  - Variability over 1 week in the urinary concentrations of metabolites of diethyl
      phthalate and di(2-ethylhexyl) phthalate among eight adults: an observational
      study.
AB  - BACKGROUND: Phthalates are metabolized and eliminated in urine within hours after
      exposure. Several reports suggest that concentrations of phthalate metabolites in
      a spot urine sample can provide a reliable estimation of exposure to phthalates
      for up to several months. OBJECTIVES: We examined inter- and intraperson and
      inter- and intraday variability in the concentrations of monoethyl phthalate
      (MEP), the major metabolite of diethyl phthalate, commonly used in personal care
      products, and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), a metabolite of
      di(2-ethylhexyl) phthalate (DEHP), a polyvinyl chloride plasticizer of which diet
      is the principal exposure source, among eight adults who collected all urine
      voids (average, 7.6 samples/person/day) for 1 week. METHODS: We analyzed the
      urine samples using online solid-phase extraction coupled to isotope dilution
      high-performance liquid chromatography-tandem mass spectrometry. RESULTS:
      Regardless of the type of void (spot, first morning, 24-hr collection), for MEP,
      interperson variability in concentrations accounted for > 75% of the total
      variance. By contrast, for MEHHP, within-person variability was the main
      contributor (69-83%) of the total variance. Furthermore, we observed considerable
      intraday variability in the concentrations of spot samples for MEHHP (51%) and
      MEP (21%). CONCLUSIONS: MEP and MEHHP urinary concentrations varied considerably
      during 1 week, but the main contributors to the total variance differed (interday
      variability, MEHHP; interperson variability, MEP) regardless of the sampling
      strategy (spot, first morning, 24-hr collection). The nature of the exposure
      (diet vs. other lifestyle factors) and timing of urine sampling to evaluate
      exposure to phthalates should be considered. For DEHP and phthalates to which
      people are mostly exposed through diet, collecting 24-hr voids for only 1 day may
      not be advantageous compared with multiple spot collections. When collecting
      multiple spot urine samples, changing the time of collection may provide the most
      complete approach to assess exposure to diverse phthalates.

PMID- 20797932
TI  - Chronic lung function decline in cotton textile workers: roles of historical and
      recent exposures to endotoxin.
AB  - BACKGROUND: Long-term occupational exposure to cotton dust that contains
      endotoxin is associated with chronic respiratory symptoms and excessive decline
      in forced expiratory volume in 1 sec (FEV1), but the mechanisms of endotoxin
      related chronic airflow obstruction remain unclear. OBJECTIVE: In the current
      study, we examined temporal aspects of the exposure-response relationship between
      airborne endotoxin exposure, longitudinal change in FEV1, and respiratory
      symptoms in a cohort of Chinese cotton textile workers. METHODS: This prospective
      cohort study followed 447 cotton textile workers from 1981 to 2006. at
      approximately 5-year intervals. We used a generalized estimating equations
      approach to model FEV1 level and respiratory symptoms as a function of past
      exposure (cumulative exposure up to the start of the most recent 5-year survey
      interval) and cumulative exposure (within the most recent interval) to
      endotoxins, after adjusting for other covariates. Models were stratified by
      active versus retired work status and by years employed before the baseline
      survey (< 5 and > or = 5 years). RESULTS AND CONCLUSIONS: Past exposure to
      endotoxin was associated with reduced FEV1 level among retired cotton workers.
      Among all cotton workers, past exposure was more strongly associated with reduced
      FEV1 for those hired < 5 years before baseline than for those who were hired > or
      = 5 years after baseline. Recent endotoxin exposure was significantly associated
      with byssinosis, chronic bronchitis, and chronic cough.

PMID- 20797933
TI  - Patient-reported communications with pharmacy staff at community pharmacies: the
      Alabama NSAID Patient Safety Study, 2005-2007.
AB  - OBJECTIVES: To examine the prevalence of patient-pharmacy staff communication
      about medications for pain and arthritis and to assess disparities in
      communication by demographic, socioeconomic, and health indicators. DESIGN:
      Descriptive, nonexperimental, cross-sectional study. SETTING: Alabama between
      2005 and 2007. PATIENTS: 687 Patients participating in the Alabama NSAID Patient
      Safety Study (age >or=50 years and currently taking a prescription nonsteroidal
      anti-inflammatory drug [NSAID]). INTERVENTION: Not applicable. MAIN OUTCOME
      MEASURES: Communication with pharmacy staff about prescription and over-the
      counter (OTC) NSAIDs was examined before and after adjustment for demographic,
      socioeconomic, and health indicators. RESULTS: For the entire cohort (n = 687),
      mean (+/-SD) age was 68.3 +/- 10.0 years, 72.8% were women, 36.4% were black, and
      31.2% discussed use of prescription pain/arthritis medications with pharmacy
      staff. Discussing use of prescription pain/arthritis medications with pharmacy
      staff differed by race/gender (P < 0.001): white men (40.3%), white women
      (34.6%), black men (30.2%), and black women (19.8%). Even after multivariable
      adjustment, black women had the lowest odds of discussing their medications with
      pharmacy staff (odds ratio 0.40 [95% CI 0.24-0.56]) compared with white men. For
      the 63.0% of participants with recently overlapping prescription and OTC NSAID
      use, communication with pharmacy staff about OTC NSAIDs use was only 13.7% and
      did not vary significantly by race/gender group. CONCLUSION: Given the complex
      risks and benefits of chronic NSAID use, pharmacists, pharmacy staff, and
      patients all are missing an important opportunity to avoid unsafe prescribing and
      decrease medication adverse events.

PMID- 20797935
TI  - Promoting the professional development of students through the creation of a
      student organization on a satellite campus: APhA-ASP.

PMID- 20797937
TI  - Effective management of pain in older adults with cancer.

PMID- 20797931
TI  - Environmental exposure, obesity, and Parkinson's disease: lessons from fat and
      old worms.
AB  - BACKGROUND: A common link has been exposed, namely, that metal exposure plays a
      role in obesity and in Parkinson's disease (PD). This link may help to elucidate
      mechanisms of neurotoxicity. OBJECTIVE: We reviewed the utility of the nematode,
      Caenorhabditis elegans, as a model organism to study neurodegeneration in obesity
      and Parkinson's disease (PD), with an emphasis on the neurotransmitter, dopamine
      (DA). DATA SOURCES: A PubMed literature search was performed using the terms
      "obesity" and any of the following: "C. elegans," "central nervous system,"
      "neurodegeneration," "heavy metals," "dopamine" or "Parkinson's disease." We
      reviewed the identified studies, including others cited therein, to summarize the
      current evidence of neurodegeneration in obesity and PD, with an emphasis on
      studies carried out in C. elegans and environmental toxins in the etiology of
      both diseases. DATA EXTRACTION AND DATA SYNTHESIS: Heavy metals and DA have both
      been linked to diet-induced obesity, which has led to the notion that the
      mechanism of environmentally induced neurodegeneration in PD may also apply to
      obesity. C. elegans has been instrumental in expanding our mechanism-based
      knowledge of PD, and this species is emerging as a good model of obesity. With
      well-established toxicity and neurogenetic assays, it is now feasible to explore
      the putative link between metal- and chemical-induced neurodegeneration.
      CONCLUSIONS: One side effect of an aging population is an increase in the
      prevalence of obesity, metabolic disorders, and neurodegenerative orders,
      diseases that are likely to co-occur. Environmental toxins, especially heavy
      metals, may prove to be a previously neglected part of the puzzle.

PMID- 20797938
TI  - Challenges in pain assessment in cognitively intact and cognitively impaired
      older adults with cancer.
AB  - PURPOSE/OBJECTIVES: To describe approaches to pain assessment in cognitively
      intact and cognitively impaired older adults with cancer. DATA SOURCES: MEDLINE
      literature search, personal reference collection, and clinical experience. DATA
      SYNTHESIS: A systematic and comprehensive pain assessment is the cornerstone of
      effective treatment strategies. Determining the effect of pain on older adults'
      ability to function is as important as rating pain intensity. Evidence-based
      recommendations exist to guide practice. CONCLUSIONS: The undertreatment of pain
      in older adults persists despite a plethora of published guidelines addressing
      pain assessment and management. Unrelieved pain affects recovery from illness and
      all aspects of life. Systematic and ongoing assessment is elementary to effective
      pain management, yet assessments frequently are neither completed nor documented.
      Because pain is subjective and individual responses to pain interventions vary
      widely and are unpredictable, assessment is vital to comprehensive pain care in
      all clinical settings. Reliable and validated pain assessment tools for
      cognitively intact and cognitively impaired older adults are available to guide
      practice. IMPLICATIONS FOR NURSING: Pain assessment is a core competency for
      nurses in all clinical settings. Comprehensive, individualized, and ongoing
      assessment provides the information necessary so that clinicians can develop
      interventions to relieve patients' pain and improve their quality of life. Nurses
      have the knowledge, skills, and tools to adequately screen and comprehensively
      assess pain in older adult patients, including those with cognitive impairment.
      By using this knowledge, nurses can change systems and practices, have a
      significant effect on improving pain care, and increase quality of life and
      function of older adults with pain.

PMID- 20797939
TI  - Practical approaches to pharmacologic management of pain in older adults with
      cancer.
AB  - PURPOSE/OBJECTIVES: To identify appropriate strategies for pharmacotherapeutic
      agents in the management of pain in older adults with cancer. DATA SOURCES:
      PubMed literature searches, personal reference collection, and clinical
      experience. DATA SYNTHESIS: To make good decisions about pain management when
      developing treatment plans for older adults, healthcare providers should focus on
      the pharmacokinetic and pharmacodynamic properties of drugs in the context of the
      physiologic changes that occur with aging. CONCLUSIONS: Unrelieved pain can have
      a detrimental effect on older adults; conversely, overmedicating can lead to an
      increased risk of adverse events. With advancing age, physiologic changes alter
      the pharmacokinetic and pharmacodynamic properties of drugs by reducing their
      absorption, changing their distribution, and modifying their metabolism and
      elimination. Also, common comorbidities increase the risk of pharmacologic
      toxicity and narrow the therapeutic window. In addition, polypharmacy-an issue
      more common in older adults-increases the complexity of prescribing and risk of
      adverse events. Consequently, older adults require individualization of their
      pharmacotherapies. Healthcare providers should consider carefully the risks and
      benefits of nonsteroidal anti-inflammatory drugs, opioids, and adjuvants before
      initiating an analgesic trial. The 2009 guidelines published by the American
      Geriatrics Society described several key principles for prescribing analgesics to
      older adults and offered specific recommendations and caveats for each drug
      class. IMPLICATIONS FOR NURSING: Current guidelines support appropriate
      management of cancer pain in older adults with specific recommendations for each
      class of analgesics as well as general prescribing principles.

PMID- 20797940
TI  - Outcome measures to evaluate the effectiveness of pain management in older adults
      with cancer.
AB  - PURPOSE/OBJECTIVES: To identify the most appropriate outcome measures to
      determine the effectiveness of pain management plans in older adults with cancer.
      DATA SOURCES: PubMed literature searches, medical and nursing textbooks, and
      clinical experience. DATA SYNTHESIS: Unrelieved chronic pain can have a
      significant impact on older adults' activity levels and their ability to
      function. Hence, effective pain management in older adults requires a
      comprehensive approach, including assessment of functional outcomes. Because the
      goals of pain management are broad, healthcare professionals should use an array
      of functional outcome measures along with pain intensity ratings to better assess
      the effectiveness of analgesic medications. CONCLUSIONS: Particularly in older
      adults, evaluation of functional outcomes provides a better indication of the
      effectiveness of pain management strategies than pain intensity ratings.
      Appropriate outcome measures for older adults in the outpatient setting include
      pain relief, physical functioning, emotional functioning, patients' ratings of
      global improvement and satisfaction with treatment, and symptoms and adverse
      effects associated with analgesic medications. IMPLICATIONS FOR NURSING:
      Healthcare providers should manage pain in older adults with cancer in an
      interdisciplinary environment with pharmacologic and nonpharmacologic
      interventions. The primary goals are decreasing pain and improving function and
      quality of life.

PMID- 20797941
TI  - Post-traumatic stress disorder related to cancer: hope, healing, and recovery.

PMID- 20797942
TI  - Acupuncture as a treatment modality for the management of cancer pain: the state
      of the science.
AB  - PURPOSE/OBJECTIVES: To explore the current state of the science regarding
      acupuncture as a treatment modality for cancer pain. DATA SOURCES: PubMed and
      CINAHL databases were searched, as were Web sites from the National Cancer
      Institute, the National Institute of Health's Complementary and Alternative
      Medicine Program, and the American Cancer Society. DATA SYNTHESIS: This article
      synthesizes nine years of published research on the use of acupuncture as an
      adjunct treatment for the management of cancer pain. CONCLUSIONS: Findings
      suggest a lack of level I evidence regarding the use of acupuncture as a cancer
      pain treatment modality. The majority of evidence is level III or higher;
      therefore, causality cannot be inferred. IMPLICATIONS FOR NURSING: Future
      research should focus on level I and level II evidence, controlling for variables
      to strengthen validity, and addressing sample size to enhance the
      generalizability of results. Nurses should be knowledgeable about the state of
      the science evidence available to assist patients in making educated decisions.

PMID- 20797943
TI  - Relationship between severity of symptoms and quality of life in patients with
      breast cancer receiving adjuvant hormonal therapy.
AB  - PURPOSE/OBJECTIVES: To describe symptoms and quality of life (QOL) of patients
      with breast cancer receiving adjuvant hormonal therapy and to examine possible
      relationships between the two measurements. DESIGN: Descriptive, correlational
      study. SETTING: An oncology clinic within a tertiary medical center in Israel.
      SAMPLE: Convenience sample of 132 patients diagnosed with primary breast cancer
      receiving hormonal therapy. METHODS: Data collection was conducted through the
      self-administered Functional Assessment of Cancer Therapy endocrine subscale and
      a sociodemographic and medical information questionnaire. MAIN RESEARCH
      VARIABLES: QOL and symptoms of hormonal therapy. FINDINGS: Ten symptoms were
      categorized by more than 20% of the participants as "very much" or "quite a bit."
      The mean QOL score for the participants was higher than that for a healthy
      population, although a correlation was found between fewer symptoms and higher
      QOL. Mood swings and irritability were the symptoms most strongly associated with
      a decrease in QOL. Patients who exercised had higher QOL scores. CONCLUSIONS:
      Adjuvant hormonal therapy did not affect the QOL of a majority of patients with
      primary breast cancer. A reduced number of symptoms indicated a higher QOL. Mood
      swings and irritability have a negative impact on QOL. IMPLICATIONS FOR NURSING:
      A need exists to design a program to follow up on hormonal symptoms and the QOL
      of patients receiving hormonal therapy and to encourage patients to engage in
      regular exercise.

PMID- 20797944
TI  - The globalization of nursing research.

PMID- 20797946
TI  - Initiative to standardize a clinical trial educational program.

PMID- 20797947
TI  - A case study on Novel H1N1.

PMID- 20797948
TI  - What does it mean to be an oncology nurse? Reexamining the life cycle concepts.
AB  - PURPOSE/OBJECTIVES: To summarize the current research pertaining to the concepts
      initially examined by the Oncology Nursing Society Life Cycle of the Oncology
      Nurse Task Force and related projects completed in 1994. DATA SOURCES: Published
      articles on the 21 concepts from the Oncology Nursing Society Life Cycle of the
      Oncology Nurse Task Force work. Research published in English from 1995-2009 was
      obtained from PubMed, CINAHL(R), PsycINFO, ISI Science, and EBSCO Health
      Source(R): Nursing/Academic Edition databases. DATA SYNTHESIS: Most of the
      concepts identified from the Oncology Nursing Society Life Cycle of the Oncology
      Nurse Task Force have been examined in the literature. Relationships and
      witnessing suffering were common concepts among studies of the meaning of
      oncology nursing. Nurses provide holistic care, and not surprisingly, holistic
      interventions have been found useful to support nurses. Interventions included
      storytelling, clinical support of nurses, workshops to find balance in lives, and
      dream work. Additional support comes from mentoring. CONCLUSIONS: The research
      identified was primarily descriptive, with very few interventions reported.
      Findings have been consistent over time in diverse countries. IMPLICATIONS FOR
      NURSING: This review indicates that although the healthcare system has changed
      significantly in 15 years, nurses' experiences of providing care to patients with
      cancer have remained consistent. The need for interventions to support nurses
      remains.

PMID- 20797949
TI  - An analysis of falls experienced by older adult patients diagnosed with cancer.
AB  - PURPOSE/OBJECTIVES: To examine themes associated with falls specific to older
      adult patients diagnosed with cancer. DESIGN: Prospective, exploratory,
      qualitative study. SETTING: A senior adult oncology program at a cancer and
      research center in the southeastern United States. SAMPLE: Men and women aged 70
      years and older with any cancer diagnosis who had experienced a fall within three
      months. METHODS: Patients were telephoned after research consent to participate
      in an interview about their falls. Frequencies were conducted on the biographic
      data. Themes were identified and grouped according to topic. MAIN RESEARCH
      VARIABLES: Eastern Cooperative Oncology Group performance status, cancer site,
      cancer treatment modality, location of fall, and fear of falls. FINDINGS: Mean
      age was 76.2 years. Most falls occurred at home (75%). The themes of physical
      problems, general weakness, and walking were found to be the most common
      motivations for falls. Themes associated with self-imposed activities as a result
      of falls included "being more careful" and "using an assistive device."
      CONCLUSIONS: Perceptions of physical problems, general weakness, and difficulty
      walking should be included in an oncology nursing fall-risk assessment.
      Exploration of perceptions concerning activities that have potentially caused a
      past fall and self-imposed activities also should be included. IMPLICATIONS FOR
      NURSING: Beyond the boundaries of a fall-risk assessment, conducting a subjective
      interview to identify the individualities of falls and fall risk is vital to
      constructing a realistic plan of care.

PMID- 20797951
TI  - Predictors of self-reported memory problems in patients with ovarian cancer who
      have received chemotherapy.
AB  - PURPOSE/OBJECTIVES: To examine the association between self-report of memory
      problems and the most commonly reported concurrent symptoms by women with ovarian
      cancer who have received chemotherapy. DESIGN: Secondary analysis. SETTING:
      Midwestern university-based school of nursing. SAMPLE: 638 women with ovarian
      cancer participating in a larger study who had received chemotherapy and 68 women
      with ovarian cancer who had not received chemotherapy. METHODS: Responses to a
      demographic questionnaire, disease and treatment history survey, and symptom
      severity index were analyzed using Pearson's correlations, hierarchical
      regression analysis, and Welch t tests for unequal sample size. MAIN RESEARCH
      VARIABLES: Self-rating of memory problems, time since chemotherapy, education
      level, and self-rating of commonly reported symptoms associated with ovarian
      cancer. FINDINGS: Nine symptoms accounted for 37% of the variance of memory
      problems (controlling for time since chemotherapy and education level).
      Significant predictors of memory problems included fatigue, mood swings, numbness
      or tingling, and sleep disturbance. Mean scores for self-reported memory problems
      were significantly different for participants who received chemotherapy compared
      to those who had not. CONCLUSIONS: Findings suggest that memory problems were
      common following chemotherapy for ovarian cancer. Additional prospective study is
      warranted to evaluate potential mechanisms underlying these symptom interactions.
      Further qualitative study may be of value to describe the patient experience and
      identify effective coping strategies. IMPLICATIONS FOR NURSING: Patient and
      family education should include information about the potential for memory
      problems following chemotherapy for ovarian cancer.

PMID- 20797952
TI  - Sword of Damocles cutting through the life stages of women with ovarian cancer.
AB  - PURPOSE/OBJECTIVES: To identify the most prevalent worries and fears of women
      diagnosed with ovarian cancer. RESEARCH APPROACH: Online survey design was used
      to elicit qualitative data. Examination of worry was a single question extracted
      from a broader investigation. SETTING: A "virtual interview" enabled women from
      12 countries and 44 states to participate in this study. PARTICIPANTS: 360
      English-speaking women aged 19-82 years with a diagnosis of ovarian cancer.
      Ninety-one percent of the women were partnered, were Caucasian, and had received
      at least some college education. The sample was equally stratified on income,
      geographic location (rural versus urban), and distance to healthcare services.
      METHODOLOGIC APPROACH: A descriptive survey was used to investigate "worry" among
      women with ovarian cancer. Colaizzi's qualitative method was used to analyze the
      narrative responses. MAIN RESEARCH VARIABLES: Worries and fears of women with
      ovarian cancer stratified by age and development stage. FINDINGS: Consistent with
      previously published studies, worry about recurrence and fear of death were
      expressed by most women, regardless of age, ethnicity, or stage of life. Other
      worries expressed by study participants varied by age and development and were
      found to correlate with the last three stages of life as described in Erikson's
      Theory of Psychosocial Development. CONCLUSIONS: Age and development stage are
      key determinants of the needs and concerns of women with ovarian cancer.
      INTERPRETATION: Age and development stage should be considered when developing an
      individualized plan of care. Because recurrence is common among this population,
      the fear of death exists regardless of age and should be explored by nurses,
      particularly during periods of remission.

PMID- 20797950
TI  - Exploring disparities and variability in perceptions and self-reported colorectal
      cancer screening among three ethnic subgroups of U. S. Blacks.
AB  - PURPOSE/OBJECTIVES: To explore perceptions of colorectal cancer (CRC) and self
      reported CRC screening behaviors among ethnic subgroups of U. S. blacks. DESIGN:
      Descriptive, cross-sectional, exploratory, developmental pilot. SETTING:
      Medically underserved areas in Hillsborough County, FL. SAMPLE: 62 men and women
      aged 50 years or older. Ethnic subgroup distribution included 22 African
      American, 20 English-speaking Caribbean-born, and 20 Haitian-born respondents.
      METHODS: Community-based participatory research methods were used to conduct face
      to-face individual interviews in the community. MAIN RESEARCH VARIABLES: Ethnic
      subgroup, health access, perceptions of CRC (e.g., awareness of screening tests,
      perceived risk, perceived barriers to screening), healthcare provider
      recommendation, and self-reported CRC screening. FINDINGS: Awareness of CRC
      screening tests, risk perception, healthcare provider recommendation, and self
      reported use of screening were low across all subgroups. However, only 55% of
      Haitian-born participants had heard about the fecal occult blood test compared to
      84% for English-speaking Caribbean-born participants and 91% for African
      Americans. Similarly, only 15% of Haitian-born respondents had had a colonoscopy
      compared to 50% for the English-speaking Caribbean and African American
      subgroups. CONCLUSIONS: This exploratory, developmental pilot study identified
      lack of awareness, low risk perception, and distinct barriers to screening. The
      findings support the need for a larger community-based study to elucidate and
      address disparities among subgroups. IMPLICATIONS FOR NURSING: Nurses play a
      major role in reducing cancer health disparities through research, education, and
      quality care. Recognition of the cultural diversity of the U. S. black population
      can help nurses address health disparities and contribute to the health of the
      community.

PMID- 20797953
TI  - A prospective randomized, placebo-controlled skin care study in women diagnosed
      with breast cancer undergoing radiation therapy.
AB  - PURPOSE/OBJECTIVES: To compare the effectiveness of three different skin care
      products versus a placebo in reducing the incidence of radiation therapy-induced
      skin reactions prophylactically. DESIGN: Prospective randomized, double-blinded,
      placebo-controlled study. SETTING: A radiation oncology department at a National
      Cancer Institute-designated comprehensive cancer center in the southeastern
      United States. SAMPLE: 208 women with breast cancer who were to receive whole
      breast radiation therapy. METHODS: Patients were invited to participate after
      radiation therapy was documented as part of their treatment plan. Patients
      applied a skin care product starting on the first day of treatment and were
      assessed weekly by their radiation oncology nurse. MAIN RESEARCH VARIABLES: Skin
      reaction score and skin product. FINDINGS: None of the products were
      statistically better than placebo in preventing skin reactions. Increases in skin
      reaction over time did not vary with treatment group for the linear (p = 0.16)
      and nonlinear (p = 0.94) effects of time and for both time components tested
      together (p = 0.41). CONCLUSIONS: Ninety-five percent of women participating in
      this study experienced a radiation therapy-induced skin reaction. IMPLICATIONS
      FOR NURSING: The development of guidelines to support safe patient care is
      encouraged because patients prefer to take action rather than do nothing.
      However, the findings do not demonstrate improved clinical outcomes with the use
      of skin care products. Healthcare providers should proactively educate patients
      about acute skin reactions and self-care strategies to minimize skin breakdown.

PMID- 20797954
TI  - Conditions and consequences of a BRCA mutation in young, single women of
      childbearing age.
AB  - PURPOSE/OBJECTIVES: To explore the experiences of young, single women who are at
      increased risk for hereditary breast and ovarian cancer (HBOC) because of a BRCA
      mutation. RESEARCH APPROACH: Qualitative. SETTING: Seven states and Canada.
      PARTICIPANTS: 11 single women aged 18-35 years who tested positive for a BRCA
      mutation. METHODOLOGIC APPROACH: Grounded theory with in-depth individual
      interviews conducted via e-mail or telephone. FINDINGS: Analysis resulted in
      three conditions and three consequences. Conditions were dating or not dating,
      time in a relationship, and physical impact of surgery or breast cancer
      treatment. Consequences were explaining their choices, experiencing a sense of
      urgency, and experiencing a sense of loss. CONCLUSIONS: Young women who are at
      risk for HBOC face a complex array of decisions after finding out that they carry
      a BRCA mutation. Being single and childless adds to this complexity.
      INTERPRETATION: Nurses can listen to young women with HBOC risk, help them
      clarify their fears and understanding of their risk, and provide nonthreatening
      support that goes beyond simply providing more information and includes a
      nonjudgmental understanding of the young women's experience.

PMID- 20797955
TI  - The cachexia assessment scale: development and psychometric properties.
AB  - PURPOSE/OBJECTIVES: To develop a tool to identify patients with cancer who suffer
      from cachexia throughout all stages of the disease. DESIGN: Tool development
      study. SETTING: Oncology day care, follow-up clinics, radiotherapy, and hospice
      home care. SAMPLE: 90 patients with cancer (25 men and 65 women). METHODS: The
      Cachexia Assessment Scale (CAS) was created based on a thorough review of the
      literature and was tested for its psychometric properties. MAIN RESEARCH
      VARIABLES: Presence of cachexia. FINDINGS: Measures of reliability were
      determined by inter-rater, test-retest, and internal consistency reliability.
      Measures of validity were content validity, criterion validity, sensitivity, and
      specificity. CONCLUSIONS: The CAS possesses adequate levels of reliability and
      validity and can be used to evaluate cachexia at all stages of cancer.
      IMPLICATIONS FOR NURSING: The CAS can be used as an assessment tool for cachexia
      in various treatment settings.

PMID- 20797958
TI  - Poststroke complex regional pain syndrome.
AB  - Poststroke Complex Regional Pain Syndrome (CRPS) affects a significant number of
      moderate to severely impaired stroke survivors. Until recently, advances in the
      assessment and management of CRPS have been limited due to the lack of a
      consensus on diagnostic criteria; however, with the development of the
      International Association for the Study of Pain diagnostic criteria, the medical
      and scientific communities are poised to make significant strides. Biomechanical
      factors and microtrauma to the hemiparetic shoulder may have a significant role
      in the genesis of CPRS, although the exact pathophysiology that links these
      triggers to the observed disease manifestation remains uncertain. Sympathetic
      dysfunction has historical importance in the CRPS literature. However, this
      appears to be only one of several possible pathophysiologic mechanisms; somatic
      nervous system dysfunction, inflammation, hypoxia, and psychological factors are
      also likely contributors to the disease process. There is no definitive treatment
      for CRPS, and most patients are treated empirically. Nevertheless, there is
      consensus that the treatment approach should be interdisciplinary with the goals
      of edema and pain control, maintenance of joint and muscle biomechanics, and
      functional restoration. As more rigorous clinical trials emerge, the treatment
      approach will become more rational with selection of interventions based on a
      specific mechanism or a combination of mechanisms responsible for a given
      individual's disease manifestation.

PMID- 20797959
TI  - Central poststroke pain syndrome.
AB  - Central poststroke pain (CPSP) syndrome is a rare complication of stroke but a
      common cause of central pain. CPSP is best managed in a well-coordinated
      interdisciplinary pain management program. Pharmacological options are available
      but none have proven optimal efficacy. Adequate pain control can be achieved with
      careful medication adjustment and a willingness to try different options in a
      stepwise approach. Motor cortex stimulation (MCS) with noninvasive or implanted
      electrodes is not currently available in the United States but has shown good
      efficacy in several clinical trials. MCS combined with medication management may
      be an option for treating CPSP in the future.

PMID- 20797960
TI  - Musculoskeletal problems in stroke survivors.
AB  - Musculoskeletal problems in stoke survivors are common reasons for disability and
      pain. Shoulder pain is present in 24% of stroke survivors among all
      complications, second only to depression in 26%. Diagnosis and treatment of the
      various shoulder pain etiologies can significantly improve quality of life in
      these patients. This article reviews the common etiologies and treatments of
      shoulder and hip pain in stroke survivors.

PMID- 20797961
TI  - Common pain syndromes in stroke patients: review of two cases.
AB  - Due to multiple neurological and musculoskeletal factors, stroke patients are at
      significant risk for the development of disabling pain syndromes. This article
      provides examples of two commonly encountered clinical situations, poststroke
      shoulder and poststroke hip pain. Appropriate use of imaging, medications,
      modalities, and injections are discussed for the purpose of enhancing management
      strategies that decrease pain and increase overall function.

PMID- 20797962
TI  - Community navigation for stroke survivors and their care partners: description
      and evaluation.
AB  - PURPOSE: To describe and evaluate a Community Stroke Navigation program. METHOD:
      A pretest-post test evaluation design was used. Community-dwelling stroke
      survivors were offered the services of a Community Stroke Navigator to assist
      them and their care partners with ongoing needs. Services included case
      coordination, emotional support, "just in time" education, coaching, advocacy,
      and accompaniment. The community reintegration and physical and emotional well
      being of the stroke survivors and their care partners were measured just prior to
      and 4 months following service provision. The Community Stroke Navigator's notes
      and qualitative interviews were analyzed to categorize the interventions.
      RESULTS: Forty-one stroke survivors and 32 care partners received navigation
      services. The stroke survivors had experienced their stroke 1 month to 30 years
      previously (mean 4.7 years, SD 6.4 years). Thirty-five stroke survivors and 26
      care partners took part in both the pretest and posttest. Posttest results
      demonstrated a small improvement in community reintegration among the stroke
      survivors but no significant change in community reintegration on the part of the
      caregivers and no alteration in physical and emotional health among either stroke
      survivors or care partners. CONCLUSION: Community Stroke Navigation has the
      potential to make an impact on community reintegration.

PMID- 20797963
TI  - The risk of motor vehicle crashes and traffic citations post stroke: a structured
      review.
AB  - BACKGROUND: Stroke impacts the domains known to be important for driving and is a
      primary condition for driving evaluation referrals. Given the high prevalence of
      stroke, the objective was to summarize the evidence regarding risk of crashes and
      traffic citations post stroke. METHODS: A structured review of six databases was
      conducted to retrieve studies that included stroke as a separate exposure from
      other disorders and measured crashes or traffic citations as an outcome. RESULTS:
      Four cohort and three case-control studies met the inclusion criteria. Five of
      the seven studies found increased odds or risk ratios ranging from 1.9 to 7.7,
      while two found an association of 0.8. Only one result was statistically
      significant (RR=2.7). One study examined the outcome traffic citations and found
      no significant association. CONCLUSION: There is cause for concern regarding
      increased risk of crashes post stroke. Future studies that examine the impact of
      stroke severity and sequelae will help health professionals, families, and those
      with stroke make informed decisions regarding driving post stroke. This review
      indicates that drivers with stroke have an increased risk of crashing compared to
      their counterparts without stroke, as demonstrated by increased risk estimates in
      five out of the seven studies that have examined this issue. This review also
      points to an urgent need for rigorous studies investigating the risk of crashes
      according to specific stroke sequelae: an understanding of crash risk based on
      stroke severity, impairments, and function will assist clinicians in making
      informed decisions regarding the need for comprehensive driving evaluation and
      the potential for driver retraining for specific subgroups.

PMID- 20797964
TI  - Predictors of returning to oral feedings after feeding tube placement for
      patients poststroke during inpatient rehabilitation.
AB  - OBJECTIVES: To identify the frequency and characteristics of patients admitted to
      inpatient rehabilitation (IPR) following a stroke who are able return to oral
      feedings and have their feeding tube (FT) removed prior to discharge from IPR,
      the timing of FT removal, and implications for outcomes. METHODS: Medical records
      were identified by admission rehabilitation impairment code (RIC) for stroke (RIC
      01), and reviews were completed by two physiatrists and two speech language
      pathologists. At random, 25% of the charts were reviewed by a second rater for
      data quality control. Measures collected during the chart review included the
      following: age, gender, onset of stroke, rehabilitation length of stay (LOS),
      admission and discharge FIM, discharge destination, diet level, and feeding tube
      status. RESULTS: One hundred forty-three patients were identified as subjects for
      this investigation who had an FT and were NPO upon IPR admission. Overall, 46.9%
      (67/143) of the patients returned to three meals daily prior to discharge from
      IPR. The mean days post stroke onset until returning to three meals daily was
      38.43 days (SD=26.36). Twenty percent (30/143) of the patients were able to have
      their FT tube removed prior to discharge from IPR. Factors associated with
      returning to three meals included gender (ie, female), longer IPR LOS, and higher
      admission FIM scores at IPR. Factors associated with removal of the feeding tube
      included a longer IPR LOS and younger age. Patients who were able to have their
      FT removed were more likely to be discharged to home. CONCLUSION: Individuals
      with longer IPR LOS were more likely to return to three meals daily and have
      their feeding tubes removed prior to discharge.

PMID- 20797965
TI  - Perspectives on poststroke sexual issues and rehabilitation needs.
AB  - PURPOSE: To study the perspectives and experiences of stroke survivors and
      partners of stroke survivors regarding sexual issues and perceived rehabilitation
      needs. METHODS: Using semi-structured interviews, 15 stroke survivors and 14
      partners of stroke survivors (median age of 65 years, range 29 to 85) provided
      information about sexual issues experienced after stroke and their perspectives
      on how to address sexual concerns in a rehabilitation setting. A qualitative
      thematic analysis was applied to transcribed interviews to identify and describe
      common themes within the data relevant to the aim of the study. A quantitative
      analysis was utilized to elucidate the frequency of themes by demographic
      characteristics that were not readily apparent using a qualitative method alone.
      RESULTS: Seven themes were identified. Two related to the effects of stroke on
      sexual life: physical/functional changes and relationship changes. Five related
      to addressing sexual issues in the process of rehabilitation: (1) difficulty in
      patients and providers talking about sexual matters, (2) little to no discussion
      of poststroke sexuality, (3) need for tailoring education to an individual or
      couple's unique needs, (4) provider rapport and competence, and (5) timing of
      poststroke sexual education. CONCLUSIONS: Poststroke sexual issues are complex
      and suggest the need for the development of a biopsychosocial model of education
      and treatment intervention. Rehabilitation programs need to evaluate the level of
      training and services provided to address poststroke sexual issues. Development
      of clinically useful poststroke sexual adjustment assessment tools and
      interventions is warranted.

PMID- 20797966
TI  - Communication confidence in persons with aphasia.
AB  - Communication confidence is a construct that has not been explored in the aphasia
      literature. Recently, national and international organizations have endorsed
      broader assessment methods that address quality of life and include
      participation, activity, and impairment domains as well as psychosocial areas.
      Individuals with aphasia encounter difficulties in all these areas on a daily
      basis in living with a communication disorder. Improvements are often reflected
      in narratives that are not typically included in standard assessments. This
      article illustrates how a new instrument measuring communication confidence might
      fit into a broad assessment framework and discusses the interaction of
      communication confidence, autonomy, and self-determination for individuals living
      with aphasia.

PMID- 20797967
TI  - Mycoviruses related to chrysovirus affect vegetative growth in the rice blast
      fungus Magnaporthe oryzae.
AB  - Mycoviruses causing impaired growth and abnormal pigmentation of the host were
      found in the rice blast fungus, Magnaporthe oryzae. Four dsRNAs, dsRNA 1 (3554
      bp), dsRNA 2 (3250 bp), dsRNA 3 (307 bp) and dsRNA 4 (3043 bp), were detected in
      isolate S-0412-II 1a of M. oryzae. By picking up single conidia of S-0412-II 1a,
      cured strains of the fungus were isolated that had completely lost the mycovirus.
      The cured strains had normal mycelial growth and pigmentation, suggesting that
      this mycovirus modulates host traits. The buoyant densities of isometric virus
      particles (~35 nm diameter) containing these dsRNAs in CsCl ranged from 1.37 to
      1.40 g cm-3. The single ORF (3384 nt) of dsRNA 1 encoded a gene product highly
      homologous to the viral RNA-dependent RNA polymerase of members of the family
      Chrysoviridae. It is noteworthy that mycovirus S-0412-II 1a was detected not only
      in host cells but also in culture supernatant. Furthermore, abnormal aggregation
      of mycelia was observed after adding the mycovirus-containing culture supernatant
      to an uninfected strain of M. oryzae and mycoviral dsRNAs were detectable from
      the aggregated mycelia. This novel dsRNA mycovirus was named Magnaporthe oryzae
      chrysovirus 1.

PMID- 20797969
TI  - Whole-genome characterization of a novel polyomavirus detected in fatally
      diseased canary birds.
AB  - Polyomaviruses of birds are aetiological agents of acute inflammatory diseases in
      non-immunocompromised hosts, which is in contrast to mammalian polyomaviruses.
      VP4, an additional structural protein encoded by the viral genomes of the known
      avian polyomaviruses, has been suggested to contribute to pathogenicity through
      loss of cells following induction of apoptosis. Four distinct bird polyomaviruses
      have been identified so far, which infect crows, finches, geese and parrots.
      Using broad-spectrum PCR, a novel polyomavirus, tentatively designated canary
      polyomavirus (CaPyV), was detected in diseased canary birds (Serinus canaria)
      that died at an age of about 40&emsp14;days. Intranuclear inclusion bodies were
      found in the liver, spleen and kidneys. The entire viral genome was amplified
      from a tissue sample using rolling-circle amplification. Phylogenetic analysis of
      the genome sequence indicated a close relationship between CaPyV and other avian
      polyomaviruses. Remarkably, an ORF encoding VP4 could not be identified in the
      CaPyV genome. Therefore, the mechanism of pathogenicity of CaPyV may be different
      from that of the other avian polyomaviruses.

PMID- 20797968
TI  - Full-length genome sequence of a simian immunodeficiency virus (SIV) infecting a
      captive agile mangabey (Cercocebus agilis) is closely related to SIVrcm infecting
      wild red-capped mangabeys (Cercocebus torquatus) in Cameroon.
AB  - Simian immunodeficiency viruses (SIVs) are lentiviruses that infect an extensive
      number of wild African primate species. Here we describe for the first time SIV
      infection in a captive agile mangabey (Cercocebus agilis) from Cameroon.
      Phylogenetic analysis of the full-length genome sequence of SIVagi-00CM312 showed
      that this novel virus fell into the SIVrcm lineage and was most closely related
      to a newly characterized SIVrcm strain (SIVrcm-02CM8081) from a wild-caught red
      capped mangabey (Cercocebus torquatus) from Cameroon. In contrast to red-capped
      mangabeys, no 24&emsp14;bp deletion in CCR5 has been observed in the agile
      mangabey. Further studies on wild agile mangabeys are needed to determine whether
      agile and red-capped mangabeys are naturally infected with the same SIV lineage,
      or whether this agile mangabey became infected with an SIVrcm strain in
      captivity. However, our study shows that agile mangabeys are susceptible to SIV
      infection.

PMID- 20797970
TI  - Epitope-specific anti-prion antibodies upregulate apolipoprotein E and disrupt
      membrane cholesterol homeostasis.
AB  - The mechanisms of neuronal degeneration induced by the transformation of normal
      cellular prion protein (PrP(C)) into disease-associated PrP(Sc) are not fully
      understood. Previous reports have demonstrated that cross-linking cellular prion
      protein by anti-PrP(C) antibodies can promote neuronal apoptosis. In this report,
      we now show that treatment of neuronal cells with anti-prion antibodies leads to
      sequestration of free cholesterol in cell membranes, significant overexpression
      of apolipoprotein E, and to cytoplasmic phospholipase A2 activation as well as to
      production of prostaglandin. These results confirm the in vivo toxic effects and
      indicate that anti-prion antibody treatment of neurons lead to deleterious
      effects. Finally, great caution should be exerted when adopting antibody-based
      therapy for prion diseases.

PMID- 20797971
TI  - In vivo ribavirin activity against severe pandemic H1N1 Influenza
      A/Mexico/4108/2009.
AB  - The use of ribavirin in influenza treatment is a matter of debate. Due to
      adamantine- and oseltamivir-resistant strains of the current pandemic H1N1
      (pdmH1N1) influenza viruses, the demand for alternative antiviral treatments has
      increased. This study demonstrated the potent antiviral effects of ribavirin in a
      mouse model of pdmH1N1 influenza infection (A/Mexico/4108/2009). It was found
      that treatment with 40 mg ribavirin kg-1 day-1 partially protected the animals if
      initiated immediately upon infection. Administration of similar concentrations on
      subsequent days or immediate therapy with lower doses efficiently delayed disease
      progression. Correlation studies showed a direct relationship between low viral
      titres in the lung during the early stages of infection with animal survival in
      ribavirin-treated animals. Reduced lung pathology in animals treated with
      ribavirin following infection also indicated the importance of immediate
      treatment. This study revealed the antiviral properties of ribavirin and these
      results justify comprehensive clinical studies for the use of ribavirin against
      influenza virus in future outbreaks.

PMID- 20797972
TI  - The effects of familism and cultural justification on the mental and physical
      health of family caregivers.
AB  - OBJECTIVES: We aimed to examine the effects of 2 factors of familism (Familial
      Obligations and Expected Support from the Family) and Cultural Justification on
      caregivers' mental and physical health as mediated by coping style. METHODS: We
      used a probability sample of 95 African American and 65 White family caregivers
      for people with dementia to test hypotheses based on the updated sociocultural
      stress and coping model using path analysis. Main outcome measures included
      depressive symptomatology, various psychological symptoms, and subjective
      physical health. RESULTS: Both Familial Obligations and Cultural Justification
      had an indirect effect on poor mental health and subjective physical health via
      avoidant coping. Expected Support from the Family had no effect on caregivers'
      health outcomes. DISCUSSION: These findings suggest that feelings of obligation
      may be accounting for a significant proportion of the negative effects of
      familism on caregivers' mental and subjective physical health. Expectations of
      familial social support may be relatively inconsequential in this process.

PMID- 20797973
TI  - Congenital left ventricular aneurysm: a cause of impaired myocardial torsion and
      peripheral thrombo-embolic events.
AB  - Congenital aneurysms of the left ventricle (LV) are rare cardiac abnormalities
      and in most instances, are asymptomatic. However, some patients may present
      cardiac rupture, tamponade, ventricular arrhythmias, and eventually sudden death.
      Herein, we describe a case of a 64-year-old male patient who was hospitalized for
      critical limb ischaemia because of an acute embolic event. Transthoracic contrast
      echocardiography revealed a congenital aneurysm of the LV apex with a small
      thrombus and a reduced LV ejection fraction. Speckle tracking imaging showed an
      impaired myocardial torsion. Diagnosis was confirmed after surgical resection of
      the aneurysm. LV torsion and ejection fraction were normalized after surgery.

PMID- 20797974
TI  - Spontaneous closure of a left ventricle pseudoaneurysm following apical venting.
AB  - Cardiac surgery is the second most frequent aetiology of left ventricular
      pseudoaneurysm (LVP). Left ventricular apical venting is a recognized cause of
      LVP. Prompt surgical treatment is usually needed since there is a high risk of
      rupture and spontaneous closure is very rare. We describe a case of spontaneous
      closure of a left ventricle pseudoaneurysm following apical venting.

PMID- 20797975
TI  - Parents' choices in banking boys' testicular tissue.
AB  - Researchers are working to derive sperm from banked testicular tissue taken from
      pre-pubertal boys who face therapies or injuries that destroy sperm production.
      Success in deriving sperm from this tissue will help to preserve the option for
      these boys to have genetically related children later in life. For the twin moral
      reasons of preserving access and equity in regard to having such children,
      clinicians and researchers are justified in offering the option to the parents of
      all affected boys. However, some parents may wish to decline the option to bank
      tissue from their boys because the technique may seem too unfamiliar or unusual,
      but over time people may become more comfortable with the technique as they have
      done with other novel assisted reproductive treatments (ARTs). Other parents may
      wish to decline the option because of moral or religious reasons. A prominent
      natural law theory holds, for example, that the ARTs that would be involved in
      using sperm derived from banked tissue to produce a child are morally
      objectionable. Some parents might not want to bank tissue in order to shield
      their son from using ARTs they see as objectionable. Clinicians and researchers
      should respect parents who wish to decline banking tissue, but parents should
      ordinarily embrace choices that protect the possible interests their sons may
      have as adult men, including the wish to have genetically related children.

PMID- 20797976
TI  - A comparative analysis of biomedical research ethics regulation systems in Europe
      and Latin America with regard to the protection of human subjects.
AB  - The European project European and Latin American Systems of Ethics Regulation of
      Biomedical Research Project (EULABOR) has carried out the first comparative
      analysis of ethics regulation systems for biomedical research in seven countries
      in Europe and Latin America, evaluating their roles in the protection of human
      subjects. We developed a conceptual and methodological framework defining 'ethics
      regulation system for biomedical research' as a set of actors, institutions,
      codes and laws involved in overseeing the ethics of biomedical research on
      humans. This framework allowed us to develop comprehensive national reports by
      conducting semi-structured interviews to key informants. These reports were
      summarised and analysed in a comparative analysis. The study showed that the
      regulatory framework for clinical research in these countries differ in scope. It
      showed that despite the different political contexts, actors involved and
      motivations for creating the regulation, in most of the studied countries it was
      the government who took the lead in setting up the system. The study also showed
      that Europe and Latin America are similar regarding national bodies and research
      ethics committees, but the Brazilian system has strong and noteworthy
      specificities.

PMID- 20797977
TI  - Students come to medical schools prepared to cheat: a multi-campus investigation.
AB  - OBJECTIVES: To investigate high school cheating experiences and attitudes towards
      academic misconduct of freshmen at all four medical schools in Croatia, as a post
      communist country in transition, with intention of raising awareness of academic
      (dis)honesty. DESIGN AND METHOD: Students were given an anonymous questionnaire
      containing 22 questions on the atmosphere of integrity at their high school, self
      reported educational dishonesty, their evaluation of cheating behaviour, and on
      their expectations about the atmosphere of integrity at their university.
      SETTING: All schools of medicine of Croatian universities (Zagreb, Rijeka, Split
      and Osijek). MAIN MEASURES: Descriptive statistics and differences in students'
      self-reported educational dishonesty, perception of cheating behaviour, and
      perception of the high school integrity atmosphere. RESULTS: Of the 761 freshmen
      attending the four medical schools, 508 (67%) completed the questionnaire: 481
      Croatian and 27 international students. Of the Croatian respondents, almost all
      (>99%) self-reported engaging in at least one behaviour of educational
      dishonesty, and 78% of respondents admitted to having frequently cheated in at
      least one form of assessed academic misconduct. Only three students admitted to
      having reported another student for cheating. For most of the questions, there
      was no significant difference in the responses among Croatian students. However,
      significant differences were found in most responses between Croatian students
      and their international counterparts, who were significantly less likely to
      engage in dishonest behaviours. No individual factor was found to correlate with
      the incidence of self-admitted dishonest behaviour. Frequent cheaters evaluated
      academic dishonesty significantly more leniently than those who did not cheat.
      CONCLUSION: Academic dishonesty of university students does not begin in higher
      education; students come to medical schools ready to cheat.

PMID- 20797978
TI  - A pilot study to examine research subjects' perception of participating in
      research in the emergency department.
AB  - STUDY OBJECTIVES: The emergency department (ED) provides an arena for patient
      enrollment into a variety of research studies even for non-critically ill
      patients. Given the types of illness, time constraints and sense of urgency that
      exists in the ED environment, concern exists about whether research subjects in
      the ED can provide full consent for participation. We sought to identify enrolled
      research subjects' perspectives on the informed consent process for research
      conducted in the ED. METHODS: This was a prospective, observational study of ED
      subjects, 18&emsp14;years or older, who had been approached to participate in
      research in the ED and who were judged to have decision-making capacity.
      Exclusions were critical illness and refusal to participate. Subjective were
      followed up within 1&emsp14;week after enrolling using structured phone
      interviews by trained interviewers. RESULTS: During the study period, 229
      eligible patients were approached to participate in both a target study and this
      study. Of these, 66% (150/229) agreed to participate in this study, at least to
      the extent of allowing us access to their demographic data. The study participant
      group was similar in terms of gender to this particular ED's patient population
      but had significantly more African-Americans and persons older than 45.
      CONCLUSION: Despite rigorous time constraints and rapid throughput times, the
      majority of subjects who consented to research participation in the ED felt that
      they were sufficiently informed and had adequate time to decide to participate.

PMID- 20797979
TI  - Developing a problem-based learning (PBL) curriculum for professionalism and
      scientific integrity training for biomedical graduate students.
AB  - A multidisciplinary faculty committee designed a curriculum to shape biomedical
      graduate students into researchers with a high commitment to professionalism and
      social responsibility and to provide students with tools to navigate complex,
      rapidly evolving academic and societal environments with a strong ethical
      commitment. The curriculum used problem-based learning (PBL), because it is
      active and learner-centred and focuses on skill and process development. Two
      courses were developed: Scientific Professionalism: Scientific Integrity
      addressed discipline-specific and broad professional norms and obligations for
      the ethical practice of science and responsible conduct of research (RCR).
      Scientific Professionalism: Bioethics and Social Responsibility focused on
      current ethical and bioethical issues within the scientific profession, and
      implications of research for society. Each small-group session examined case
      scenarios that included: (1) learning objectives for professional norms and
      obligations; (2) key ethical issues and philosophies within each topic area; (3)
      one or more of the RCR instructional areas; and (4) at least one type of moral
      reflection. Cases emphasised professional standards, obligations and underlying
      philosophies for the ethical practice of science, competing interests of
      stakeholders and oversight of science (internal and external). To our knowledge,
      this is the first use of a longitudinal, multi-semester PBL course to teach
      scientific integrity and professionalism. Both faculty and students endorsed the
      active learning approach for these topics, in contrast to a compliance-based
      approach that emphasises learning rules and regulations.

PMID- 20797980
TI  - Relationship of arterial stiffness and early mild diastolic heart failure in
      general middle and aged population.
AB  - AIMS: The brachial-ankle pulse wave velocity (baPWV) has been recognized as a
      marker that reflects arterial stiffness. We conducted an investigation to
      evaluate whether baPWV is independently associated with early mild diastolic
      heart failure (DHF) in a general middle and aged population. METHODS AND RESULTS:
      From 1 July 2009 until 31 August 2009, we investigated 2095 subjects for the
      relevant factors of heart failure in the Lujiazui Community, Shanghai. The baPWV,
      echocardiography, and blood sampling were performed in the morning after a 12 h
      overnight fast. A total of 1929 subjects had the complete data, including
      questionnaire, age, gender, baPWV, brain natriuretic peptide, and E/A ratio.
      Early mild DHF was defined as a left ventricular ejection fraction >50%, E/A
      ratio <0.8, and E/E' <= 8; finally, 482 subjects with early mild DHF and 1282
      subjects with non-DHF entered into analysis. Among 1764 subjects, 31.6% of the
      subjects were male (average age was 58.0 +/- 12.3), 35.8% of the subjects had
      hypertension, the average body mass index (BMI) was 24.2 +/- 3.3 kg/m(2), baPWV
      was 1513.0 (1329.1, 1763.5) cm/s, and the baPWV was significantly correlated with
      the E/A ratio (r = -0.39, P < 0.01). There was a difference of the baPWV [1456.0
      (1295.3, 1698.3) vs. 1670.5 (1465.6, 1910.8) cm/s] between the non-DHF group and
      the early mild DHF group (P < 0.01). Multiple logistic-regression analyses
      demonstrated that age, male gender, BMI, baPWV, posterior left ventricular wall
      thickness (PVWT), interventricular septal thickness (IVST), E/E' ratio, left
      ventricular mass index (LVMI), systolic blood pressure (>=140 mmHg), and
      diastolic blood pressure (>=90 mmHg) were independently correlated with early
      mild DHF. CONCLUSIONS: The increased arterial stiffness is associated with early
      mild DHF in a general middle and aged population independently of age, male
      gender, BMI, PVWT, IVST, E/E' ratio, LVMI, and high blood pressure. The non
      invasive techniques described may allow serial measurements to be made over time
      to monitor baPWV changes in arteries provided the introduction of anti
      arteriosclerosis therapy.

PMID- 20797981
TI  - Three-dimensional imaging in the context of minimally invasive and transcatheter
      cardiovascular interventions using multi-detector computed tomography: from pre
      operative planning to intra-operative guidance.
AB  - The rapid expansion of less invasive surgical and transcatheter cardiovascular
      procedures for a wide range of cardiovascular conditions, including coronary,
      valvular, structural cardiac, and aortic disease has been paralleled by novel
      three-dimensional (3-D) approaches to imaging. Three-dimensional imaging allows
      acquisition of volumetric data sets and subsequent off-line reconstructions along
      unlimited 2-D planes and 3-D volumes. Pre-procedural 3-D imaging provides
      detailed understanding of the operative field for surgical/interventional
      planning. Integration of imaging modalities during the procedure allows real-time
      guidance. Because computed tomography routinely acquires 3-D data sets, it has
      been one of the early imaging modalities applied in the context of surgical and
      interventional planning. This review describes the continuum of applications from
      pre-operative planning to procedural integration, based on the emerging
      experience with computed tomography and rotational angiography, respectively. At
      the same time, the potential adverse effects of imaging with X-ray-based
      tomographic or angiographic modalities are discussed. It is emphasized that the
      role of imaging guidance in this context remains unclear and will need to be
      evaluated in clinical trials. This is in particular true, because data showing
      improved outcome or even non-inferiority for most of the emerging transcatheter
      procedures are still lacking.

PMID- 20797982
TI  - Contained aortic root rupture after transcatheter aortic valve implantation.

PMID- 20797983
TI  - Inference on treatment effects from a randomized clinical trial in the presence
      of premature treatment discontinuation: the SYNERGY trial.
AB  - The Superior Yield of the New Strategy of Enoxaparin, Revascularization, and
      GlYcoprotein IIb/IIIa inhibitors (SYNERGY) was a randomized, open-label,
      multicenter clinical trial comparing 2 anticoagulant drugs on the basis of time
      to-event endpoints. In contrast to other studies of these agents, the primary,
      intent-to-treat analysis did not find evidence of a difference, leading to
      speculation that premature discontinuation of the study agents by some subjects
      may have attenuated the apparent treatment effect and thus to interest in
      inference on the difference in survival distributions were all subjects in the
      population to follow the assigned regimens, with no discontinuation. Such
      inference is often attempted via ad hoc analyses that are not based on a formal
      definition of this treatment effect. We use SYNERGY as a context in which to
      describe how this effect may be conceptualized and to present a statistical
      framework in which it may be precisely identified, which leads naturally to
      inferential methods based on inverse probability weighting.

PMID- 20797984
TI  - Caloric restriction delays cardiac ageing in rats: role of mitochondria.
AB  - AIMS: We tested whether long-term caloric restriction (CR) corrects pre-existing
      manifestations of cardiac ageing in rats. METHODS AND RESULTS: The age-specific
      effects of CR (-40%, 6 months) on mortality, left ventricular (LV) function,
      mitochondrial function, oxidative damage, and apoptosis were analysed in young (6
      + 6 months) and senescent rats (24 + 6 months). CR in senescent rats
      significantly reduced mortality. LV and cardiomyocyte hypertrophy were reduced
      together with the mRNA expression and plasma concentrations of overload
      indicators BNP/ANP. Mitochondrial function was improved, resulting in lower
      oxidative damage and apoptotic activation. In particular, the pro-apoptotic Bcl
      xS/Bcl-xL isoform pattern, mitochondrial translocation of Bax, release of
      cytochrome C into cytosol, and caspase-9 activation were reduced in comparison to
      age-matched rats on the control diet. However, CR resulted only in minor changes
      in young rats. Serum obtained from old control or CR rats was used for in vitro
      experiments. H9C2 cardiomyoblasts and adult rat ventricular cardiomyocytes
      preconditioned with CR serum demonstrated a low Bcl-xS/Bcl-xL ratio. H9C2 cells
      were resistant against H(2)O(2)-mediated loss of mitochondrial membrane
      potential, apoptosis activation, and reduced cell viability. Thus, beneficial
      effects of CR are mediated through circulating factors and can be mimicked with
      CR serum. However, this protection critically depended on a high Bcl-xL protein
      expression as seen after siRNA-mediated Bcl-xL knockdown. CONCLUSION: CR is
      cardioprotective in senescent myocardium by correcting pre-existing mitochondrial
      dysfunction and apoptotic activation and by preventing deterioration in LV
      function. Therefore, interventions that mimic these effects of CR may represent
      an additional therapeutic option for the aged or failing heart.

PMID- 20797985
TI  - Cardiomyocyte NF-kappaB p65 promotes adverse remodelling, apoptosis, and
      endoplasmic reticulum stress in heart failure.
AB  - AIMS: the role of nuclear factor (NF)-kappaB in heart failure (HF) is not well
      defined. We sought to determine whether myocyte-localized NF-kappaB p65
      activation in HF exacerbates post-infarction remodelling and promotes maladaptive
      endoplasmic reticulum (ER) stress. METHODS AND RESULTS: non-transgenic (NTg) and
      transgenic (Tg) mice with myocyte-restricted overexpression of a phosphorylation
      resistant inhibitor of kappaBalpha (IkappaBalpha(S32A,S36A)) underwent coronary
      ligation (to induce HF) or sham operation. Over 4 weeks, the remote myocardium of
      ligated hearts exhibited robust NF-kappaB activation that was almost exclusively
      p65 beyond 24 h. Compared with sham at 4 weeks, NTg HF hearts were dilated and
      dysfunctional, and exhibited hypertrophy, fibrosis, up-regulation of inflammatory
      cytokines, increased apoptosis, down-regulation of ER protein chaperones, and up
      regulation of the ER stress-activated pro-apoptotic factor CHOP. Compared with
      NTg HF, Tg-IkappaBalpha(S32A,S36A) HF mice exhibited: (i) improved survival,
      chamber remodelling, systolic function, and pulmonary congestion, (ii) markedly
      diminished NF-kappaB p65 activation, cytokine expression, and fibrosis, and (iii)
      a three-fold reduction in apoptosis. Moreover, Tg-IkappaBalpha(S32A,S36A) HF
      hearts exhibited maintained expression of ER chaperones and CHOP when compared
      with sham. In cardiomyocytes, NF-kappaB activation was required for ER stress
      mediated apoptosis, whereas abrogation of myocyte NF-kappaB shifted the ER stress
      response to one of adaptation and survival. CONCLUSION: persistent myocyte NF
      kappaB p65 activation in HF exacerbates cardiac remodelling by imparting pro
      inflammatory, pro-fibrotic, and pro-apoptotic effects. p65 modulation of cell
      death in HF may occur in part from NF-kappaB-mediated transformation of the ER
      stress response from one of adaptation to one of apoptosis.

PMID- 20797986
TI  - Plasma parathyroid hormone and risk of congestive heart failure in the community.
AB  - AIMS: In experimental studies parathyroid hormone (PTH) has been associated with
      underlying causes of heart failure (HF) such as atherosclerosis, left ventricular
      hypertrophy, and myocardial fibrosis. Individuals with increased levels of PTH,
      such as primary or secondary hyperparathyroidism patients, have increased risk of
      ischaemic heart disease and HF. Moreover, increasing PTH is associated with worse
      prognosis in patients with overt HF. However, the association between PTH and the
      development HF in the community has not been reported. METHODS AND RESULTS: In a
      prospective, community-based study of 864 elderly men without HF or valvular
      disease at baseline (mean age 71 years, the ULSAM study) the association between
      plasma (P)-PTH and HF hospitalization was investigated adjusted for established
      HF risk factors (myocardial infarction, hypertension, diabetes,
      electrocardiographic left ventricular hypertrophy, smoking, and
      hypercholesterolaemia) and variables reflecting mineral metabolism (S-calcium, S
      phosphate, P-vitamin D, S-albumin, dietary calcium and vitamin D intake, physical
      activity, glomerular filtration rate, and blood draw season). During follow-up
      (median 8 years), 75 individuals were hospitalized due to HF. In multivariable
      Cox-regression analyses, higher P-PTH was associated with increased HF
      hospitalization (hazard ratio for 1-SD increase of PTH, 1.41, 95% CI 1.12-1.77, P
      = 0.003). Parathyroid hormone also predicted hospitalization in participants
      without apparent ischaemic HF and in participants with normal P-PTH. CONCLUSION:
      In a large community-based sample of elderly men, PTH predicted HF
      hospitalizations, also after accounting for established risk factors and mineral
      metabolism variables.  Our data suggest a role for PTH in the development of HF
      even in the absence of overt hyperparathyroidism.

PMID- 20797987
TI  - International variations in the clinical, diagnostic, and treatment
      characteristics of emergency department patients with acute heart failure
      syndromes.
AB  - AIMS: Results from investigations in one area of the world may not translate to
      another if patient characteristics and practices differ. We examine differences
      in the presentation and management of emergency department (ED) patients with
      dyspnoea from acute heart failure syndromes (AHFS) between the USA, Western
      Europe, and Eastern Europe. METHODS AND RESULTS: The URGENT Dyspnoea study was a
      multinational prospective observational study of dyspnoeic ED patients with AHFS
      from 18 countries. Acute heart failure syndrome patients from the USA and Western
      and Eastern Europe underwent dyspnoea assessments within 1 h of the first
      physician evaluation. Patient characteristics, evaluation, and treatments were
      compared between geographical regions using analysis of variance and chi(2)
      tests. Four hundred and ninety-three patients with AHFS met the inclusion
      criteria. Participants in the USA were more frequently non-white, younger, on
      chronic beta-blocker therapy, and with an ejection fraction <=40% when compared
      with Eastern and Western Europe. Patients from Eastern Europe were more likely to
      present with de novo heart failure and have ischaemic electrocardiogram changes.
      Pulmonary oedema was more common on chest radiograph in Western Europe, but
      natriuretic peptide levels were elevated in all three regions. Diuretic use was
      similar across all the regions. Intravenous nitroglycerin was used more
      frequently in Eastern (32.8%) and Western Europe (24.4%) compared with the USA
      (2.5%). CONCLUSION: International differences in AHFS presentations and
      management between regions suggest results from clinical trials in one region may
      not translate directly to another. These differences should be considered when
      designing trials and interpreting the results from clinical investigations.

PMID- 20797989
TI  - Fibrates reduce the risk of major cardiovascular and coronary events compared
      with placebo, but do not affect risk of cardiovascular or all-cause mortality.

PMID- 20797988
TI  - Association of blood lactate with type 2 diabetes: the Atherosclerosis Risk in
      Communities Carotid MRI Study.
AB  - BACKGROUND: Accumulating evidence implicates insufficient oxidative capacity in
      the development of type 2 diabetes. This notion has not been well tested in
      large, population-based studies. METHODS: To test this hypothesis, we assessed
      the cross-sectional association of plasma lactate, an indicator of the gap
      between oxidative capacity and energy expenditure, with type 2 diabetes in 1709
      older adults not taking metformin, who were participants in the Atherosclerosis
      Risk in Communities (ARIC) Carotid MRI Study. RESULTS: The prevalence of type 2
      diabetes rose across lactate quartiles (11, 14, 20 and 30%; P for trend <0.0001).
      Following adjustment for demographic factors, physical activity, body mass index
      and waist circumference, the relative odds of type 2 diabetes across lactate
      quartiles were 0.98 [95% confidence interval (CI) 0.59-1.64], 1.64 (95% CI 1.03
      2.64) and 2.23 (95% CI 1.38-3.59), respectively. Furthermore, lactate was
      associated with higher fasting glucose among non-diabetic adults. CONCLUSIONS:
      Plasma lactate was strongly associated with type 2 diabetes in older adults.
      Plasma lactate deserves greater attention in studies of oxidative capacity and
      diabetes risk.

PMID- 20797990
TI  - High blood pressure while taking antithrombotic medication is associated with an
      increased risk of developing intracranial haemorrhage.

PMID- 20797991
TI  - Specific clinical findings, including coma, neck stiffness and seizures, increase
      the likelihood of haemorrhagic stroke, but no combination of features is
      definitively diagnostic.

PMID- 20797992
TI  - Meta analysis suggests that folic acid supplementation does not reduce risk of
      stroke, but there may be some benefit when given in combination with vitamins B6
      and B12 and in primary prevention.

PMID- 20797993
TI  - Topical NSAIDs provide effective relief of acute musculoskeletal pain compared to
      placebo, with no increase in risk of adverse effects.

PMID- 20797994
TI  - Analysis of the willow root system by electrical impedance spectroscopy.
AB  - Information on plant roots is increasingly needed for understanding and managing
      plants under various environmental conditions, including climate change. Several
      methods have been developed to study fine roots but they are either destructive
      or cumbersome, or may not be suitable for studies of fine root functionality.
      Electrical impedance, resistance, and capacitance have been proposed as possible
      non-destructive measures for studying roots. Their use is limited by a lack of
      knowledge concerning the electrical circuit of the system. Electrical impedance
      spectroscopy (EIS) was used for hydroponically raised willows (Salix schwerinii)
      to estimate the root system size. The impedance spectra were investigated in
      three experimental set-ups and the corresponding appropriate lumped models were
      formulated. The fit of the proposed lumped models with the measured impedance
      spectra data was good. The model parameters were correlated with the contact area
      of the roots and/or stems raised in the hydroponic solution. The EIS method
      proved a useful non-destructive method for assessing root surface area. This work
      may be considered to be a new methodological contribution to understanding root
      systems and their functions in a non-destructive manner.

PMID- 20797995
TI  - Convergence of the 26S proteasome and the REVOLUTA pathways in regulating
      inflorescence and floral meristem functions in Arabidopsis.
AB  - The 26S proteasome is a large multisubunit proteolytic complex, regulating growth
      and development in eukaryotes by selective removal of short-lived regulatory
      proteins. Here, it is shown that the 26S proteasome and the transcription factor
      gene REVOLUTA (REV) act together in maintaining inflorescence and floral meristem
      (IM and FM) functions. The characterization of a newly identified Arabidopsis
      mutant, designated ae4 (asymmetric leaves1/2 enhancer4), which carries a mutation
      in the gene encoding the 26S proteasome subunit, RPN2a, is reported. ae4 and rev
      have minor defects in phyllotaxy structure and meristem initiation, respectively,
      whereas ae4 rev demonstrated strong developmental defects. Compared with the rev
      single mutant, an increased percentage of ae4 rev plants exhibited abnormal
      vegetative shoot apical and axillary meristems. After flowering, ae4 rev first
      gave rise to a few normal-looking flowers, and then flowers with reduced numbers
      of all types of floral organs. In late reproductive development, instead of
      flowers, the ae4 rev IM produced numerous filamentous structures, which contained
      cells seen only in the floral organs, and then carpelloid organs. In situ
      hybridization revealed that expression of the WUSCHEL and CLAVATA3 genes was
      severely down-regulated or absent in the late appearing ae4 rev primordia, but
      the genes were strongly expressed in top-layer cells of inflorescence tips.
      Double mutant plants combining rev with other 26S proteasome subunit mutants,
      rpn1a and rpn9a, resembled ae4 rev, suggesting that the 26S proteasome might act
      as a whole in regulating IM and FM functions.

PMID- 20797996
TI  - Augmentation of abscisic acid (ABA) levels by drought does not induce short-term
      stomatal sensitivity to CO2 in two divergent conifer species.
AB  - The stomata of conifers display very little short-term response to changes in
      atmospheric CO(2) concentration (C(a)), whereas the stomatal responses of
      angiosperms to C(a) increase in response to water stress. This behaviour of
      angiosperm stomata appears to be dependent on foliar levels of abscisic acid
      (ABA(f)). Here two alternative explanations for the stomatal insensitivity of
      conifers to C(a) are tested: that conifers have either low ABA(f) or a higher or
      absent threshold for ABA-induced sensitivity. The responsiveness of stomatal
      conductance (g(s)) to a sequence of transitions in C(a) (386, 100, and 600 MUmol
      mol(-1)) was recorded over a range of ABA(f) in an angiosperm and two divergent
      conifer species. The different ABA levels were induced by a mild drought cycle.
      Although the angiosperm and conifer species showed similar proportional increases
      in ABA(f) following drought, conifer stomata remained insensitive to changes in
      C(a) whereas angiosperm stomata showed enhanced sensitivity with increasing
      ABA(f). The conifers, however, had much higher ABA(f) prior to drought than the
      angiosperm species, suggesting that non-sensitivity to C(a) in these conifers was
      due to an absent or inactive response/signalling pathway rather than insufficient
      ABA(f).

PMID- 20797997
TI  - Misregulation of the LOB domain gene DDA1 suggests possible functions in auxin
      signalling and photomorphogenesis.
AB  - The LATERAL ORGAN BOUNDARIES DOMAIN (LBD) gene family encodes plant-specific
      transcription factors. In this report, the LBD gene DOWN IN DARK AND AUXIN1
      (DDA1), which is closely related to LATERAL ORGAN BOUNDARIES (LOB) and ASYMMETRIC
      LEAVES2 (AS2), was characterized. DDA1 is expressed primarily in vascular tissues
      and its transcript levels were reduced by exposure to exogenous indole-3-acetic
      acid (IAA or auxin) and in response to dark exposure. Analysis of a T-DNA
      insertion line, dda1-1, in which the insertion resulted in misregulation of DDA1
      transcripts in the presence of IAA and in the dark revealed possible functions in
      auxin response and photomorphogenesis. dda1-1 plants exhibited reduced
      sensitivity to auxin, produced fewer lateral roots, and displayed aberrant
      hypocotyl elongation in the dark. Phenotypes resulting from fusion of a
      transcriptional repression domain to DDA1 suggest that DDA1 may act as both a
      transcriptional activator and a transcriptional repressor depending on the
      context. These results indicate that DDA1 may function in both the auxin
      signalling and photomorphogenesis pathways.

PMID- 20797998
TI  - Plant physiology and proteomics reveals the leaf response to drought in alfalfa
      (Medicago sativa L.).
AB  - Despite its relevance, protein regulation, metabolic adjustment, and the
      physiological status of plants under drought is not well understood in relation
      to the role of nitrogen fixation in nodules. In this study, nodulated alfalfa
      plants were exposed to drought conditions. The study determined the
      physiological, metabolic, and proteomic processes involved in photosynthetic
      inhibition in relation to the decrease in nitrogenase (N(ase)) activity. The
      deleterious effect of drought on alfalfa performance was targeted towards
      photosynthesis and N(ase) activity. At the leaf level, photosynthetic inhibition
      was mainly caused by the inhibition of Rubisco. The proteomic profile and
      physiological measurements revealed that the reduced carboxylation capacity of
      droughted plants was related to limitations in Rubisco protein content,
      activation state, and RuBP regeneration. Drought also decreased amino acid
      content such as asparagine, and glutamic acid, and Rubisco protein content
      indicating that N availability limitations were caused by N(ase) activity
      inhibition. In this context, drought induced the decrease in Rubisco binding
      protein content at the leaf level and proteases were up-regulated so as to
      degrade Rubisco protein. This degradation enabled the reallocation of the Rubisco
      derived N to the synthesis of amino acids with osmoregulant capacity. Rubisco
      degradation under drought conditions was induced so as to remobilize Rubisco
      derived N to compensate for the decrease in N associated with N(ase) inhibition.
      Metabolic analyses showed that droughted plants increased amino acid (proline, a
      major compound involved in osmotic regulation) and soluble sugar (D-pinitol)
      levels to contribute towards the decrease in osmotic potential (Psi(s)). At the
      nodule level, drought had an inhibitory effect on N(ase) activity. This decrease
      in N(ase) activity was not induced by substrate shortage, as reflected by an
      increase in total soluble sugars (TSS) in the nodules. Proline accumulation in
      the nodule could also be associated with an osmoregulatory response to drought
      and might function as a protective agent against ROS. In droughted nodules, the
      decrease in N(2) fixation was caused by an increase in oxygen resistance that was
      induced in the nodule. This was a mechanism to avoid oxidative damage associated
      with reduced respiration activity and the consequent increase in oxygen content.
      This study highlighted that even though drought had a direct effect on leaves,
      the deleterious effects of drought on nodules also conditioned leaf
      responsiveness.

PMID- 20798000
TI  - Open and closed inflorescences: more than simple opposites.
AB  - The absence of a terminal flower in inflorescences ('open inflorescences') is
      currently explained by the maintenance of putative stem-cells in the central zone
      (CZ) of the inflorescence meristem (IM) governed by the CLAVATA-WUSCHEL
      regulatory loop. Disruption of this regulatory pathway, as in Arabidopsis
      TERMINAL FLOWER LOCUS 1 mutants, leads to terminal flower production. However,
      recent studies in other taxa reveal novel mechanisms of inflorescence
      termination; for example, the SEPALLATA-like MADS-box floral identity gene
      GERBERA REGULATOR OF CAPITULUM DEVELOPMENT 2 in Gerbera excludes the retention of
      a CZ as an ontogenetic cause for the openness of these inflorescences. Moreover,
      comparative histological studies show that the retention of a CZ in the IM,
      mostly a feature of the 'typical open families', is absent in open inflorescences
      of other families. Concerning these groups, new evidence suggests that spatial
      constraints at the IM could play a role at the time when terminal flower
      production (or not) is determined. This indicates that the multiple loss and re
      gain of the terminal flower in angiosperms is necessarily based on more than one
      ontogenetic pathway.

PMID- 20797999
TI  - Haem oxygenase delays programmed cell death in wheat aleurone layers by
      modulation of hydrogen peroxide metabolism.
AB  - Haem oxygenase-1 (HO-1) confers protection against a variety of oxidant-induced
      cell and tissue injury in animals and plants. In this report, it is confirmed
      that programmed cell death (PCD) in wheat aleurone layers is stimulated by GA and
      prevented by ABA. Meanwhile, HO activity and HO-1 protein expression exhibited
      lower levels in GA-treated layers, whereas the hydrogen peroxide (H(2)O(2))
      content was apparently increased. The pharmacology approach illustrated that
      scavenging or accumulating H(2)O(2) either delayed or accelerated GA-induced PCD.
      Furthermore, pretreatment with the HO-1 specific inhibitor, zinc protoporphyrin
      IX (ZnPPIX), before exposure to GA, not only decreased HO activity but also
      accelerated GA-induced PCD significantly. The application of the HO-1 inducer,
      haematin, and the enzymatic reaction product of HO, carbon monoxide (CO) aqueous
      solution, both of which brought about a noticeable induction of HO expression,
      substantially prevented GA-induced PCD. These effects were reversed when ZnPPIX
      was added, suggesting that HO in vivo played a role in delaying PCD. Meanwhile,
      catalase (CAT) and ascorbate peroxidase (APX) activities or transcripts were
      enhanced by haematin, CO, or bilirubin (BR), the catalytic by-product of HO. This
      enhancement resulted in a decrease in H(2)O(2) production and a delay in PCD. In
      addition, the antioxidants butylated hydroxytoluene (BHT), dithiothreitol (DTT),
      and ascorbic acid (AsA) were able not only to delay PCD but also to mimic the
      effects of haematin and CO on HO up-regulation. Overall, the above results
      suggested that up-regulation of HO expression delays PCD through the down
      regulation of H(2)O(2) production.

PMID- 20798001
TI  - What is the best strategy to reduce the burden of occupational asthma and allergy
      in bakers?
AB  - RATIONALE: Insight into the effectiveness of intervention strategies will help
      realise a decrease in the occupational disease burden from (allergic) respiratory
      diseases in the bakery population. OBJECTIVES: To use a simulation model to
      assess the impact of different intervention strategies on the disease burden of
      the bakery population over time. METHODS: A recently developed dynamic population
      based model was used to prospectively evaluate the impact on disease burden
      resulting from different intervention strategies. We distinguished interventions
      based on exposure reductions for flour dust and fungal alpha-amylase, health
      surveillance combined with reduction in exposure, and pre-employment screening.
      MAIN RESULTS: The impact of most interventions on disease burden was limited,
      generally less than 50% for lower respiratory symptoms and disabling occupational
      asthma. Only the rigorous health surveillance strategy, identifying workers who
      are sensitised or report upper respiratory symptoms and decreasing their
      individual exposures by 90% shortly after diagnosis, resulted in a decrease of
      almost 60% in disease burden after 20 years. CONCLUSIONS: This study demonstrates
      that different intervention strategies have substantially different impacts on
      the burden of disease. The time window during which changes occur differs
      considerably between strategies. This information can assist policy makers in
      their choice of intervention and gives guidance for achievable reductions in
      disease burden.

PMID- 20798002
TI  - Blood lead at currently acceptable levels may cause preterm labour.
AB  - OBJECTIVES: Although occupational and environmental exposures to lead have been
      dramatically reduced in recent decades, adverse pregnancy outcomes have been
      observed at 'acceptable' levels of blood lead concentrations (<= 10 MUg/dl).
      METHODOLOGY: Blood samples were collected from 348 singleton pregnant women, aged
      16-35 years, during the first trimester of pregnancy (8-12 weeks) for lead
      measurement by inductively coupled plasma-mass spectrometry. Subjects were
      followed up and divided into two groups (preterm and full-term deliveries)
      according to duration of gestation. RESULTS: The average (range) and geometric
      means of blood lead levels were 3.8 (1.0-20.5) and 3.5 MUg/dl, respectively.
      Blood lead level was significantly (p<0.05) higher in mothers who delivered
      preterm babies than in those who delivered full-term babies (mean+/-SD: 4.46+/
      1.86 and 3.43+/-1.22 MUg/dl, respectively). Logistic regression analysis
      demonstrated that a 1 unit increase in blood lead levels led to an increased risk
      of preterm birth (OR 1.41, 95% CI 1.08 to 1.84). CONCLUSION: Adverse pregnancy
      outcomes may occur at blood lead concentrations below the current acceptable
      level.

PMID- 20798003
TI  - Mortality from diabetes and ischaemic heart disease in textile workers.
AB  - BACKGROUND: To explore explanations for elevated mortality from diabetes among
      male garment manufacturers and repairers in England and Wales during 1979-1990,
      analysis was extended by 10 years, looking also at other textile workers and at
      deaths from ischaemic heart disease (IHD). METHODS: Data on some 3.5 million
      deaths were used to compute proportional mortality ratios (PMRs) for diabetes and
      IHD, standardised for age and social class, in 10 textile-associated job groups,
      with additional analyses by place of birth for 1993-2000. RESULTS: Male mortality
      from diabetes was elevated in nine of the 10 textile jobs, with overall PMRs of
      147 (95% CI 131 to 165) during 1979-90 and 170 (95% CI 144 to 199) during 1991
      2000. Proportional mortality from IHD was also consistently high. Female
      mortality from both diseases was close to that for other occupations. In both
      sexes, mortality from diabetes and IHD was increased among people born in the
      Indian subcontinent (PMRs 353 and 139 in men; 262 and 130 in women). In men, the
      proportion of deceased textile workers born in the Indian subcontinent (11.4%)
      was much higher than for all occupations (1.8%), but not in women (1.1% vs 0.7%).
      PMRs for male textile workers standardised for place of birth were lower but
      still significantly elevated (133, 95% CI 110 to 159 for diabetes; 109, 95% CI
      105 to 114 for IHD). CONCLUSIONS: No obvious occupational hazard explains the
      increased risk specific to men across a wide range of textile occupations. One
      possible explanation is uncontrolled residual confounding related to place of
      birth. This could be tested through suitably designed morbidity surveys.

PMID- 20798004
TI  - Mortality from liver cancer and leukaemia among polyvinyl chloride workers in
      Taiwan: an updated study.
AB  - OBJECTIVES: To investigate types of cancer caused by occupational exposure to
      vinyl chloride monomer (VCM) and the temporal mortality trends of these cancers
      in workers from polyvinyl chloride (PVC) manufacturing factories in Taiwan, with
      follow-up of the cohort extended by 15 years, from 1980 to 2007. Methods A
      retrospective cohort study of workers from six PVC factories in Taiwan was
      conducted. 3336 male PVC workers were enrolled and further linked with the
      National Mortality Registry and National Household Registry databases.
      Standardised mortality ratios (SMR) with 95% CIs were calculated and compared to
      the general Taiwanese male population. Cause-specific mortality between two study
      periods, 1980-1997 and 1998-2007, was compared. Six-year moving averages of the
      SMRs were calculated to examine mortality trends. RESULTS: Liver cancer mortality
      increased during 1989-1994 (SMR 1.90, 95% CI 1.01 to 3.25), reached a peak during
      1991-1996 (SMR 2.31, 95% CI 1.39 to 3.61) and became non-significant during 1994
      1999 (SMR 1.42, 95% CI 0.80 to 2.34). Leukaemia mortality significantly increased
      during 1984-1989 (SMR 6.06, 95% CI 1.24 to 17.53), reached a peak during 1985
      1990 (SMR 7.56, 95% CI 2.06 to 19.35) and became non-significant during 1991-1996
      (SMR 3.24, 95% CI 0.39 to 11.69). The mortality trend for haemolymphopoietic
      cancer showed a similar pattern to that of leukaemia. CONCLUSIONS: VCM may
      increase the risk of liver cancer and leukaemia. When VCM exposure was controlled
      at worksites, mortality from these cancers returned to background levels.

PMID- 20798005
TI  - Circadian variation of heart rate variability among welders.
AB  - OBJECTIVE: To compare the circadian variation of hourly heart rate variability
      (HRV) on work and non-workdays among boilermaker construction workers. METHOD: A
      panel study of 18 males monitored by 24-h ambulatory ECG over 44 observation-days
      on paired work and non-workdays was conducted. ECGs were analysed and the SD of
      normal-to-normal beats index (SDNN(i)) was calculated from 5-min data and
      summarised hourly. SDNN(i)s over work and non-workdays were compared using linear
      mixed-effects models to account for repeated measures and harmonic regression to
      account for circadian variation. RESULTS: Both work and non-work hourly HRV
      exhibited circadian variation with an increase in the evening and a decrease in
      the afternoon. SDNN(i) was lower on workdays as compared with non-workdays with
      the largest, statistically significant differences observed between 10:00 and
      16:00, during active working. Lower SDNN(i), albeit smaller yet statistically
      significant differences, was also observed in the evening hours following work
      (17:00-21:00) and early morning (4:00). In regression models using all time
      periods, an average workday SDNN(i) was 8.1 ms (95% CI -9.8 to -6.3) lower than
      non-workday SDNN(i). The circadian pattern of HRV exhibited two peaks which
      differed on work and non-workdays. CONCLUSION: While workday and non-workday HRV
      followed a circadian pattern, decreased HRV and variation of the circadian
      pattern were observed on workdays. Declines and changes in the circadian pattern
      of HRV is a concern among this exposed population.

PMID- 20798006
TI  - Is potroom asthma due more to sulphur dioxide than fluoride? An inception cohort
      study in the Australian aluminium industry.
AB  - OBJECTIVES: Although an asthma-like syndrome has been recognised in aluminium
      smelter workers for over 70 years, the causal agent has been difficult to
      identify. METHODS: An inception cohort study was conducted at two Australian
      aluminium smelters where 446 employees participated over a period of 9 years.
      Cumulative exposures between interviews were estimated from job histories using a
      task exposure matrix based on measurements in the smelters. Participants
      completed an MRC respiratory questionnaire, spirometry and methacholine challenge
      test. Data were analysed with generalised estimating equations to allow for
      repeated measurements of each participant. RESULTS: Wheeze and chest tightness,
      the two symptoms most closely related to asthma, showed associations with
      occupational exposures. SO(2) exposure was significantly associated with these
      symptoms, bronchial hyper-responsiveness (BHR) to methacholine (a feature of
      asthma), airflow limitation (reduced forced expiratory volume in 1 second/forced
      vital capacity ratio) and longitudinal decline in lung function. Fluoride
      exposure was associated with the same outcomes, but less strongly. Inhalable dust
      and the benzene soluble fraction (BSF) were associated with symptoms of asthma
      and BHR. Although many of the exposures were highly correlated, further modelling
      suggested that of the known respiratory irritants, SO(2) was more likely than
      fluoride to be primarily responsible for the symptoms observed. Fluoride,
      inhalable dust and SO(2) were the most important airborne contaminants associated
      with effects on lung function. CONCLUSIONS: The observed effects were detected at
      contaminant levels within occupational exposure standards, so further reductions
      are required, particularly in SO(2) exposures.

PMID- 20798007
TI  - Prevalence of airflow limitation among employees in Norwegian smelters: a
      longitudinal study.
AB  - AIMS: To investigate the association between airflow limitation and occupational
      exposure and to compare a fixed limit with an age adjusted limit for airflow
      limitation. METHODS: 3924 employees in 24 Norwegian smelters and related
      workplaces were investigated annually over 5 years (n=16, 570) using spirometry
      and a respiratory questionnaire on smoking habits and job category. Employees
      working full time on the production line were classified as line operators;
      subjects who never worked on the production line were regarded as non-exposed. A
      job exposure matrix (JEM) was available in most smelters. Airflow limitation was
      expressed as (i) forced expiratory volume in 1 s/forced vital capacity
      (FEV(1)/FVC ratio) <0.7 and (ii) FEV(1)/FVC ratio less than the lower limit of
      normal (LLN). Longitudinal analyses on the prevalence of airflow limitation were
      performed using a generalised linear mixed model. RESULTS: The prevalence of
      airflow limitation was stable during follow-up. The OR of airflow limitation
      during follow-up was 1.24 (95% CI 1.03 to 1.50) in line operators compared with
      unexposed subjects for FEV(1)/FVC ratio <0.7 and 1.44 (1.14 to 1.81) for
      FEV(1)/FVC ratio <LLN. A dose-response relationship was also found between
      prevalence of airflow limitation and dust exposure. The annual decline in FEV(1)
      was -77.5 (SD 99.9) ml/year in subjects with FEV(1)/FVC ratio <0.7 and -83.8
      (114.2) ml/year in subjects with FEV(1)/FVC ratio <LLN. CONCLUSION: Prevalence of
      airflow limitation was higher in exposed than non-exposed employees. Both the
      FEV(1)/FVC ratio <0.7 and FEV(1)/FVC ratio <LLN identify subjects with
      accelerated annual decline in FEV(1).

PMID- 20798008
TI  - Radiation doses from global fallout and cancer incidence among reindeer herders
      and Sami in Northern Finland.
AB  - OBJECTIVES: People in the Arctic regions are one of the most heavily exposed
      population from the global fallout from atmospheric atomic bomb testing of the
      1950s and 1960s due to their diet rich in reindeer meat in which radionuclides
      accumulate. We estimated the effect of the radioactive fallout and ethnicity on
      the cancer incidence in Northern Finland. METHODS: A cohort of the Arctic
      population in Finland (n=34,653) was identified through the Population Register
      Centre with grouping by reindeer herding status, ethnicity and radiation
      exposure. Annual average radiation doses, based on (137)Cs whole-body
      measurements, were assigned by birth year, gender and reindeer herder status.
      Incident cancer cases of a priori selected cancer types in the study cohort
      during 1971-2005 were identified from the Finnish Cancer Registry. RESULTS: A
      total of 2630 cancer cases were observed versus 3073 expected on the basis of
      incidence rates in Northern Finland (standardised incidence ratio (SIR) was 0.86
      with 95% CI of 0.82 to 0.89). For the indigenous Sami people SIR was even lower,
      0.60 (95% CI 0.50 to 0.71). None of the cancer sites was significantly associated
      with the lifetime cumulative radiation dose. The SIR for the combined group of
      radiation-related cancer sites increased with the cumulative radiation dose
      received before 15 years of age (p=0.004). CONCLUSION: Despite the low overall
      cancer incidence in the Arctic population and ethnic Sami people in Finland and
      lack of association between the lifetime cumulative radiation exposure from
      global radioactive fallout and cancer incidence, we found some indication of an
      increased cancer risk associated with radiation exposure received during
      childhood. Potential underestimation and misclassification of the radiation dose
      may affect the results and the findings should be interpreted with caution.

PMID- 20798009
TI  - Comparison of occupational exposure assessment methods in a case-control study of
      lead, genetic susceptibility and risk of adult brain tumours.
AB  - OBJECTIVES: There is great interest in evaluating gene-environment interactions
      with chemical exposures, but exposure assessment poses a unique challenge in case
      control studies. Expert assessment of detailed work history data is usually
      considered the best approach, but it is a laborious and time-consuming process.
      We set out to determine if a less intensive method of exposure assessment (a job
      exposure matrix (JEM)) would produce similar results to a previous analysis that
      found evidence of effect modification of the association between expert-assessed
      lead exposure and risk of brain tumours by a single nucleotide polymorphism in
      the ALAD gene (rs1800435). METHODS: We used data from a study of 355 patients
      with glioma, 151 patients with meningioma and 505 controls. Logistic regression
      models were used to examine associations between brain tumour risk and lead
      exposure and effect modification by genotype. We evaluated Cohen's kappa,
      sensitivity and specificity for the JEM compared to the expert-assessed exposure
      metrics. RESULTS: Although effect estimates were imprecise and driven by a small
      number of cases, we found evidence of effect modification between lead exposure
      and ALAD genotype when using expert- but not JEM-derived lead exposure estimates.
      kappa Values indicated only modest agreement (<0.5) for the exposure metrics,
      with the JEM indicating high specificity (~0.9) but poor sensitivity (~0.5).
      Disagreement between the two methods was generally due to having additional
      information in the detailed work history. CONCLUSION: These results provide
      preliminary evidence suggesting that high quality exposure data are likely to
      improve the ability to detect genetic effect modification.

PMID- 20798011
TI  - Occupational exposure to electromagnetic fields and sex-differential risk of
      uveal melanoma.
AB  - OBJECTIVES: The association between occupational exposure to electromagnetic
      fields (EMF) and the risk of uveal melanoma was investigated in a case-control
      study in nine European countries. METHODS: Incident cases of uveal melanoma and
      population as well as hospital controls were included and frequency matched by
      country, 5-year birth cohort and sex. Subjects were asked whether they had worked
      close to high-voltage electrical transmission installations, computer screens and
      various electrical machines, or in complex electrical environments. Measurements
      of two Scandinavian job-exposure matrices were applied to estimate lifelong
      cumulative EMF exposure. Unconditional logistic regression analyses, stratified
      by sex and eye colour were calculated, adjusting for several potential
      confounders. RESULTS: 293 patients with uveal melanoma and 3198 control subjects
      were interviewed. Women exposed to electrical transmission installations showed
      elevated risks (OR 5.81, 95% CI 1.72 to 19.66). Positive associations with
      exposure to control rooms were seen among men and women, but most risk increases
      were restricted to subjects with dark iris colour. Application of published EMF
      measurements revealed stronger risk increases among women compared to men. Again,
      elevated risks were restricted to subjects with dark eye colour. CONCLUSION:
      Although based on a low prevalence of exposure to potential occupational sources
      of EMF, our data indicate that exposed dark-eyed women may be at particular risk
      for uveal melanoma.

PMID- 20798010
TI  - Occupation and occupational exposure to endocrine disrupting chemicals in male
      breast cancer: a case-control study in Europe.
AB  - OBJECTIVES: Male breast cancer is a rare disease of largely unknown aetiology. In
      addition to genetic and hormone-related risk factors, a large number of
      environmental chemicals are suspected of playing a role in breast cancer. The
      identification of occupations or occupational exposures associated with an
      increased incidence of breast cancer in men may help to identify mammary
      carcinogens in the environment. METHODS: Occupational risk factors for male
      breast cancer were investigated in a multi-centre case-control study conducted in
      eight European countries which included 104 cases and 1901 controls. Lifetime
      work history was obtained during in-person interviews. Occupational exposures to
      endocrine disrupting chemicals (alkylphenolic compounds, phthalates,
      polychlorinated biphenyls and dioxins) were assessed on a case-by-case basis
      using expert judgement. RESULTS: Male breast cancer incidence was particularly
      increased in motor vehicle mechanics (OR 2.1, 95% CI 1.0 to 4.4) with a dose
      effect relationship with duration of employment. It was also increased in paper
      makers and painters, forestry and logging workers, health and social workers, and
      furniture manufacture workers. The OR for exposure to alkylphenolic compounds
      above the median was 3.8 (95% CI 1.5 to 9.5). This association persisted after
      adjustment for occupational exposures to other environmental oestrogens.
      CONCLUSION: These findings suggest that some environmental chemicals are possible
      mammary carcinogens. Petrol, organic petroleum solvents or polycyclic aromatic
      hydrocarbons are suspect because of the consistent elevated risk of male breast
      cancer observed in motor vehicle mechanics. Endocrine disruptors such as
      alkylphenolic compounds may play a role in breast cancer.

PMID- 20798012
TI  - Traffic-related air pollution and pregnancy outcomes in the Dutch ABCD birth
      cohort study.
AB  - OBJECTIVES: There is growing evidence for an adverse effect of maternal exposure
      to air pollution on pregnancy outcomes. As European data on this topic are
      limited, the aim of this study was to evaluate the impact of maternal exposure to
      traffic-related air pollution during different periods of pregnancy on preterm
      birth and fetal growth. METHODS: We estimated maternal residential exposure to
      NO(2) during pregnancy (entire pregnancy and trimesters) for 7600 singleton
      births participating in the Amsterdam Born Children and their Development (ABCD)
      prospective birth cohort study by means of a temporally adjusted land-use
      regression model. Associations between air pollution concentrations and preterm
      birth and fetal growth (expressed as small for gestational age and term birth
      weight) were analysed by means of logistic and linear regression models with and
      without adjustment for maternal physiological, lifestyle and sociodemographic
      characteristics. RESULTS: There was no indication of an increase in preterm birth
      among highly exposed women. Children of mothers with NO(2) levels in the highest
      exposure category on average had the highest term birth weight of all children
      and were among those with the lowest risk of being small for gestational age with
      little indication of a dose-response relationship. CONCLUSIONS: In this study,
      there is no evidence for a harmful effect of estimated maternal exposure to
      traffic-related air pollution during pregnancy on pregnancy outcomes such as
      preterm birth, small for gestational age and term birth weight.

PMID- 20798013
TI  - Should we warn against night shifts to prevent breast cancer?

PMID- 20798014
TI  - Incidence of extrapleural malignant mesothelioma and asbestos exposure, from the
      Italian national register.
AB  - OBJECTIVES: The epidemiology of extrapleural malignant mesothelioma is rarely
      discussed and the risk of misdiagnosis and the very low incidence complicate the
      picture. This study presents data on extrapleural malignant mesothelioma from the
      Italian National Mesothelioma Register (ReNaM). METHODS: ReNaM works on a
      regional basis, searching for cases and interviewing subjects to investigate
      asbestos exposure. Classification and code criteria for certainty of diagnosis
      and exposure modalities are set by national guidelines. Between 1993 and 2004,
      681 cases were collected. Incidence measures and exposure data refer to the ReNaM
      database. Age-standardised rates were estimated by the direct method using the
      Italian resident population in 2001. Correlations between the incidence of
      pleural and non-pleural malignant mesothelioma for the 103 Italian provinces were
      analysed. RESULTS: Standardised incidence rates (Italy, 2004, per million
      inhabitants) were 2.1 and 1.2 cases for the peritoneal site (in men and women,
      respectively), 0.2 cases for the tunica vaginalis testis, and 0.1 in the
      pericardial site, varying widely in different parts of the country. Mean age at
      diagnosis for all extrapleural malignant mesothelioma cases was 64.4 years and
      the men/women ratio was 1.57:1. Median latency was over 40 years for all
      extrapleural sites combined. The correlation between pleural and peritoneal
      mesothelioma was 0.71 (Pearson's r coefficient, p<0.001). Modalities of exposure
      to asbestos fibres were investigated for 392 cases. CONCLUSIONS: The rarity of
      the disease, the low specificity of diagnosis and difficulties in identifying the
      modalities of asbestos exposure call for caution in discussing aetiological
      factors other than asbestos.

PMID- 20798015
TI  - A long term study of pulmonary function among US refractory ceramic fibre
      workers.
AB  - BACKGROUND: Cross-sectional studies have shown declines in lung function among
      refractory ceramic fibre (RCF) workers with increasing fibre exposure. This study
      followed current and former workers (n=1396) for up to 17 years and collected
      5243 pulmonary function tests. METHODS: Cumulative fibre exposure and production
      years were categorised into exposure levels at five manufacturing locations.
      Conventional longitudinal models did not adequately partition age-related changes
      from other time-dependent variables. Therefore, a restricted cubic spline model
      was developed to account for the non-linear decline with age. RESULTS: Cumulative
      fibre >60 fibre-months/cc showed a significant loss in lung function at the first
      test. When results were examined longitudinally, cumulative exposure was
      confounded with age as workers with the highest cumulative exposure were
      generally older. A longitudinal model adjusted by age groups was implemented to
      control for this confounding. No consistent longitudinal loss in lung function
      was observed with RCF exposure. Smoking, initial weight and weight increase were
      significant factors. CONCLUSION: No consistent decline was observed
      longitudinally with exposure to RCF, although cross-sectional and longitudinal
      findings were discordant. Confounding and accelerated lung function declines with
      ageing and the correlation of multiple time-dependent variables should be
      considered in order to minimise error and maximise precision. An innovative
      statistical methodology for these types of data is described.

PMID- 20798016
TI  - Fast and specific detection of moderate long-term changes in occupational blood
      exposures.
AB  - OBJECTIVES: Hospital surveillance systems have been established to monitor
      occupational blood exposures. We compare short-term monitoring with long-term
      monitoring of data analysis over 11 years and 21 institutions to identify
      variations in the number of reported exposures. METHODS: Short-term monitoring
      examines the current number of exposures compared to their average over previous
      years. Long-term monitoring detects trends over several years by various exposure
      characteristics (place, staff, procedure, etc) through estimating rates of change
      and using the best linear unbiased predictors (BLUPs) to prevent artefactual
      trends due to the many categories for each characteristic. Graphical
      representations of estimated rates help detect change and differences in rates of
      change. RESULTS: Annual monitoring allowed detection of significant changes in
      the number of reported exposures. Long-term monitoring identified moderate trends
      over time. The BLUP corrected the estimate of each specific annual rate of change
      and allowed all other rates to reduce the random variability around the mean
      change for more specificity. League tables showed significant increases or
      decreases compared to no change. League tables for two-by-two comparisons allowed
      reliable comparisons between estimates of the rates of change, although with
      spurious ranking. Funnel plots enabled quick detection of changes in trends
      within specified confidence intervals. Long-term trends agreed with the dominant
      type of annual changes over the 11&emsp14;years but were not as sensitive.
      CONCLUSIONS: The two methods have different uses. Both are helpful for assessing
      short-term sudden and long-term minor changes in number of exposures, possibly
      reflecting the success or otherwise of introducing specific safety devices or
      guidelines.

PMID- 20798017
TI  - Ozone, heat and mortality: acute effects in 15 British conurbations.
AB  - BACKGROUND: Acute associations between mortality and ozone are largely accepted,
      though recent evidence is less conclusive. Evidence on ozone-heat interaction is
      sparse. We assess effects of ozone, heat, and their interaction, on mortality in
      Britain. METHODS: Acute effects of summer ozone on mortality were estimated using
      data from 15 conurbations in England and Wales (May-September, 1993-2003). 2-day
      means of daily maximum 8-h ozone were entered into case series analyses,
      controlling for particulate matter with aerodynamic diameter of <10 MUm, natural
      cubic splines of temperature, and other factors. Heat effects were estimated,
      comparing adjusted mortality rates at 97.5th and 75th percentiles of 2-day mean
      temperature. A separate model employed interaction terms to assess whether ozone
      effects increased on 'hot days' (where 2-day mean temperature exceeded the whole
      year 95th percentile). Other heat metrics, and non-linear ozone effects, were
      also examined. RESULTS: Adverse ozone and heat effects occurred in nearly all
      conurbations. The mean mortality rate ratio for heat effect across conurbations
      was 1.071 (1.050-1.093). The mean ozone rate ratio was 1.003 per 10 MUg/m(3)
      ozone increase (95% CI 1.001 to 1.005). On 'hot days' the mean ozone effect
      reached 1.006 (1.002-1.009) per 10 MUg/m(3), though ozone-heat interaction was
      significant in London only. On substituting maximum for mean temperature, the
      overall ozone effect reduced to null, though evidence remained of effects on hot
      days, particularly in London. An estimated ozone effect threshold was below
      current guidelines in 'mean temperature' models. CONCLUSION: While heat showed
      robust effects on summer mortality, estimates for ozone depended upon the
      modelling of temperature. However, there was some evidence that ozone effects
      were worse on hot days, whichever temperature measure was used.

PMID- 20798018
TI  - Use of mobile phones and changes in cognitive function in adolescents.
AB  - BACKGROUND: Several studies have investigated the impact of mobile phone exposure
      on cognitive function in adults. However, children and adolescents are of special
      interest due to their developing nervous systems. METHODS: Data were derived from
      the Australian Mobile Radiofrequency Phone Exposed Users' Study (MoRPhEUS) which
      comprised a baseline examination of year 7 students during 2005/2006 and a 1-year
      follow-up. Sociodemographic and exposure data were collected with a
      questionnaire. Cognitive functions were assessed with a computerised test battery
      and the Stroop Color-Word test. RESULTS: 236 students participated in both
      examinations. The proportion of mobile phone owners and the number of voice calls
      and short message services (SMS) per week increased from baseline to follow-up.
      Participants with more voice calls and SMS at baseline showed less reductions in
      response times over the 1-year period in various computerised tasks. Furthermore,
      those with increased voice calls and SMS exposure over the 1-year period showed
      changes in response time in a simple reaction and a working memory task. No
      associations were seen between mobile phone exposure and the Stroop test.
      CONCLUSIONS: We have observed that some changes in cognitive function,
      particularly in response time rather than accuracy, occurred with a latency
      period of 1 year and that some changes were associated with increased exposure.
      However, the increased exposure was mainly applied to those who had fewer voice
      calls and SMS at baseline, suggesting that these changes over time may relate to
      statistical regression to the mean, and not be the effect of mobile phone
      exposure.

PMID- 20798019
TI  - Symptoms of psychological distress and suicidal ideation among banana workers
      with a history of poisoning by organophosphate or n-methyl carbamate pesticides.
AB  - OBJECTIVES: Neuropsychiatric disorders and increased suicide rates have been
      associated with exposure to cholinesterase inhibiting organophosphates. This
      study examined symptoms of psychological distress, including suicidal ideation,
      among banana workers in Costa Rica previously exposed to a cholinesterase
      inhibiting pesticide. METHODS: 78 workers who had received medical attention 1-3
      years previously for occupational pesticide poisoning were recruited: 54 had been
      exposed to organophosphate, 24 to carbamate, and 43 and 35, respectively, had
      single and multiple poisoning episodes with a cholinesterase inhibitor. Referents
      were 130 non-poisoned workers randomly selected from company payrolls.
      Psychological distress symptoms during the month prior to interview were obtained
      using the Brief Symptom Inventory (BSI), which has a general severity index and
      nine subscale scores. Differences in abnormal BSI scores (T score>=63) were
      assessed through multivariate logistic regression for all poisoned and for
      subcategories of poisoned as compared to non-poisoned workers. RESULTS:
      Organophosphate poisoned workers reported significantly more symptoms than non
      poisoned on all but one symptom dimension. Significant trends of increasing
      symptoms with increasing number of previous poisonings were seen for
      somatisation, obsessive-compulsiveness, interpersonal sensitivity, depression and
      anxiety. Carbamate poisoned workers only had increased scores for somatisation.
      The ORs for suicidal thoughts were: all poisoned 3.58 (95% CI 1.45 to 8.84);
      organophosphate poisoned 3.72 (1.41 to 9.81); carbamate poisoned 2.57 (0.73 to
      9.81); and 2.65 and 4.98, respectively for 1 and >=2 poisonings (trend p=0.01).
      CONCLUSIONS: This cross-sectional study showed a relationship between acute
      occupational poisoning with organophosphates and psychological distress including
      suicidal ideation. Stronger designs are needed to address causality.

PMID- 20798020
TI  - The impact of ill health on exit from paid employment in Europe among older
      workers.
AB  - OBJECTIVE: To determine the impact of ill health on exit from paid employment in
      Europe among older workers. METHODS: Participants of the Survey on Health and
      Ageing in Europe (SHARE) in 11 European countries in 2004 and 2006 were selected
      when 50-63 years old and in paid employment at baseline (n=4611). Data were
      collected on self-rated health, chronic diseases, mobility limitations, obesity,
      smoking, alcohol use, physical activity and work characteristics. Participants
      were classified into employed, retired, unemployed and disabled at the end of the
      2-year follow-up. Multinomial logistic regression was used to estimate the effect
      of different measures of ill health on exit from paid employment. RESULTS: During
      the 2-year follow-up, 17% of employed workers left paid employment, mainly
      because of early retirement. Controlling for individual and work related
      characteristics, poor self-perceived health was strongly associated with exit
      from paid employment due to retirement, unemployment or disability (ORs from 1.32
      to 4.24). Adjustment for working conditions and lifestyle reduced the significant
      associations between ill health and exit from paid employment by 0-18.7%. Low
      education, obesity, low job control and effort-reward imbalance were associated
      with measures of ill health, but also risk factors for exit from paid employment
      after adjustment for ill health. CONCLUSION: Poor self-perceived health was
      strongly associated with exit from paid employment among European workers aged 50
      63 years. This study suggests that the influence of ill health on exit from paid
      employment could be lessened by measures targeting obesity, problematic alcohol
      use, job control and effort-reward balance.

PMID- 20798021
TI  - Secondhand tobacco smoke in bars and restaurants in Santiago, Chile: evaluation
      of partial smoking ban legislation in public places.
AB  - OBJECTIVE: To compare air nicotine concentrations according to the smoking policy
      selected by bars/restaurants in Santiago, Chile before and after the enactment of
      partial smoking ban legislation in 2007 (establishments could be smoke free, have
      segregated (mixed) smoking and non-smoking areas, or allow smoking in all areas).
      METHODS: The study measured air nicotine concentrations over 7 days to
      characterise secondhand smoke exposure in 30 bars/restaurants in 2008.
      Owner/manager interviews and physical inspections were conducted. RESULTS: Median
      IQR air nicotine concentrations measured in all venues were 4.38 (0.61-13.62)
      MUg/m(3). Air nicotine concentrations were higher in bars (median 7.22, IQR 2.48
      15.64 MUg/m(3)) compared to restaurants (1.12, 0.15-9.22 MUg/m(3)). By smoking
      status, nicotine concentrations were higher in smoking venues (13.46, 5.31-16.87
      MUg/m(3)), followed by smoking areas in mixed venues (9.22, 5.09-14.90 MUg/m(3))
      and non-smoking areas in mixed venues (0.99, 0.19-1.27 MUg/m(3)). Air nicotine
      concentrations were markedly lower in smoke-free venues (0.12, 0.11-0.46
      MUg/m(3)). After adjustment for differences in volume and ventilation, air
      nicotine concentrations were 3.2, 35.5 and 56.2 times higher in non-smoking areas
      in mixed venues, smoking areas in mixed venues and smoking venues, respectively,
      compared to smoke-free venues. CONCLUSIONS: Exposure to secondhand smoke remains
      high in bars and restaurants in Santiago, Chile. These findings demonstrate that
      the partial smoking ban legislation enacted in Chile in 2007 provides no
      protection to employees working in those venues. Enacting a comprehensive smoke
      free legislation which protects all people from exposure to secondhand smoke in
      all public places and workplaces is urgently needed.

PMID- 20798022
TI  - Workplace smoking restrictions in China: results from a six county survey.
AB  - OBJECTIVE: To determine the coverage of smoking restriction policies in indoor
      workplaces in China and to assess the relationships between these restrictive
      policies and secondhand smoke (SHS) exposure and smoking behaviours. METHODS: A
      cross-sectional household survey was conducted in six counties in Sichuan,
      Jiangxi and Henan provinces in 2004. Using a standardised questionnaire,
      information on demographic characteristics, knowledge, attitudes and behaviours
      related to smoking and SHS exposure was collected through face-to-face interviews
      by trained local investigators among 12 036 respondents. Of respondents, 2698
      individuals worked mainly indoors and were included in data analysis. RESULTS:
      Only 28.5% of respondents reported that indoor workplaces had a smoke-free
      policy. Even when respondents reported smoke-free policies, 41.1% smokers
      reported that they were non-compliant with policies and smoked at work. In
      addition, 32.0% of non-smokers reported being exposed to SHS at work despite
      smoke-free policies. Non-smokers who reported no smoking restriction policies
      were 3.7 times more likely to be exposed to SHS than those working in smoke-free
      workplaces (adjusted OR 3.7, 95% CI 1.3 to 10.1). On average, respondents
      complying with smoke-free policies smoked 3.8 fewer cigarettes than those
      reporting no policies in their workplaces at a marginally non-significant level
      (p=0.06) (adjusted mean difference -3.8, 95% CI -8.0 to 0.5). CONCLUSIONS: In
      China, few workplaces have implemented policies to restrict smoking, and, even in
      workplaces that have policies, workers report exposure to SHS while at their
      places of employment. Many workers report a lack of compliance with smoke-free
      policies. China needs better implementation of SHS policies to promote
      compliance. Working to improve implementation of smoke-free policies would
      promote cessation since Chinese smokers who were compliant with these efforts
      reported smoking fewer cigarettes per day.

PMID- 20798023
TI  - Participation in a population-based physical activity programme as an aid for
      smoking cessation: a randomised trial.
AB  - OBJECTIVES: Exercise combined with nicotine therapy may help smoking cessation
      and minimise weight gain after quitting. Low participation in vigorous-intensity
      physical activity programmes precludes their population-wide applicability. In a
      randomised controlled trial, we tested whether a population-based moderate
      intensity physical activity programme increases quit rates among sedentary
      smokers receiving nicotine therapy. METHODS: Participants (n=481; 57% male; mean
      age, 42.2 years (SD 10.1); mean cigarette consumption, 27 (SD 10.2) per day) were
      offered a nine-week smoking cessation programme consisting of a weekly 15-minute
      counselling session and the prescription of nicotine replacement therapy. In
      addition, participants in the physical activity group (n=229) also took part in a
      programme of moderate-intensity physical activity implemented at the national
      level, and offering nine weekly 60-minute sessions of physical activity. To
      ensure equal contact conditions, participants in the control group (n=252)
      attended weekly 60-minute health behaviour education sessions unrelated to
      physical activity. The primary outcome was continuous CO-verified smoking
      abstinence rates at 1-year follow-up. RESULTS: Continuous smoking abstinence
      rates were high and similar in the physical activity group and the control group
      at the end of the intervention (47% versus 46%, p=0.81) and at 1-year follow-up
      (27% versus 29%, p=0.71). The mean weight gain after one year was 4.4 kg and 6.2
      kg among sustained quitters of the physical activity and control groups,
      respectively (p=0.06). CONCLUSION: Participation in a population-based moderate
      intensity physical activity programme for 9 weeks in addition to a comprehensive
      smoking cessation programme did not significantly increase smoking cessation
      rates. A non-significant reduction in weight gain was observed among participants
      who quit smoking in the physical activity group. TRIAL REGISTRATION:
      ClinicalTrials.gov; US National Institutes for Health (available online at
      http://clinicaltrials.gov/; CLINICAL TRIAL REGISTRATION NUMBER: NCT00521391).

PMID- 20798024
TI  - Taking environmental epidemiology to the next level: understanding complex
      systems.

PMID- 20798025
TI  - Cancer survivors' return to work: importance of work accommodations and
      collaboration between stakeholders.

PMID- 20798026
TI  - Trends in blood lead levels in UK workers, 1995-2007.
AB  - OBJECTIVES: This study evaluated blood lead data (including zinc protoporphyrin
      (ZPP) and haemoglobin levels) collected at the UK's Health and Safety Laboratory
      (HSL) in order to determine temporal changes in occupational exposure to lead
      between 1995 and 2007. METHODS: A total of 20,889 blood lead measurements and
      accompanying ZPP and haemoglobin results from 8810 workers at 972 companies from
      routine samples received by HSL over the period 1995-2007 were analysed. Time
      trends in blood lead levels for each industry sector were estimated using
      Bayesian mixed effects modelling. RESULTS: Reductions in median blood levels over
      the period 1995-2007 were seen in every sector except for those samples forwarded
      by occupational health providers, and range from 1.6% per year for workers in the
      smelting industry to 12% per year for workers in pottery and glazing industries.
      An overall reduction of 3.1% per year across all industries was determined. The
      percentage of results above the current UK suspension limit of 60 microg/dl fell
      from 4.8% in 1995 to 0.6% in 2007. ZPP and blood lead exhibited a strong
      association, but no significant correlation was found between blood lead and
      haemoglobin. CONCLUSIONS: Occupational exposure to lead has fallen across UK
      industries in recent years, although it remains substantially above background
      levels. There is evidence that many workers are exposed to elevated lead levels
      over a long period of time and this deserves renewed consideration now that
      inorganic lead has been reclassified as a probable human carcinogen.

PMID- 20798027
TI  - Economic evaluation of a workplace intervention for sick-listed employees with
      distress.
AB  - OBJECTIVES: To evaluate the cost effectiveness, cost utility and cost benefit of
      a workplace intervention compared with usual care for sick-listed employees with
      distress. METHODS: An economic evaluation was conducted alongside a randomised
      controlled trial. Employees with distress and who were sick-listed for 2-8 weeks
      were randomised to a workplace intervention (n=73) or to usual care (n=72). The
      workplace intervention is a stepwise process involving the sick-listed employee
      and their supervisor, aimed at formulating a consensus-based plan for return to
      work (RTW). The effect outcomes were lasting RTW and quality-adjusted life years
      (QALYs). Healthcare utilisation was measured over 12 months. Cost effectiveness
      analyses (CEA) and cost utility analyses (CUA) were conducted from the societal
      perspective and cost benefit analyses (CBA) from the employer perspective.
      Bootstrapping techniques were used to estimate cost and effect differences,
      related CIs, and cost effectiveness and cost utility ratios. Cost effectiveness
      planes were presented and subgroup analyses were performed. RESULTS: CEA and CUA
      revealed no statistically significant differences in lasting RTW, QALYs or costs.
      The CBA indicated a statistically significant higher cost of occupational health
      services in the workplace intervention group. The workplace intervention was not
      cost effective according to the CEA, CUA and CBA. CONCLUSIONS: Widespread
      implementation of the workplace intervention for sick-listed employees with
      distress is not recommended because there was no economic benefit compared with
      usual care. Future trials should confirm if the workplace intervention is cost
      effective for the subgroup employees who intended to return to work despite
      symptoms. This trial has been registered at the Dutch National Trial Register
      ISRCTN92307123.

PMID- 20798028
TI  - Cytogenotoxicity in uroepithelial cells of women exposed to mercury in a mining
      area.
AB  - OBJECTIVE: To investigate biomarkers of cytogenotoxicity in women exposed to
      mercury in a mining area. Mercury has been associated with cytogenotoxicity in
      human and animal models but has not been considered carcinogenic in humans, even
      though genotoxic effects following exposure to inorganic mercury compounds have
      been observed. METHODS: A cross-sectional study and micronucleus assay in
      uroepithelial cells were performed in 104 women (12-84 years of age). First urine
      void samples were taken to determine creatinine-adjusted mercury levels in urine
      (HgUCr), to isolate cells and to quantify cytogenetic damage. RESULTS: The
      geometric average level for HgUCr was 4.9 microg/g (range, 0.4-85). In the
      generalised linear model, after controlling for other co-variables, we observed
      that for each 10 microg/g increase in HgUCr, the OR of developing a genotoxic
      effect was 2.37 (95% CI 1.79 to 2.84), while for cytotoxic damage in
      uroepithelial cells the OR was 1.34 (95% CI 1.10 to 1.79). These results suggest
      a possible association between cytogenotoxicity and HgUCr. CONCLUSION: Living in
      a mining area with exposure to inorganic mercury and having higher mercury levels
      in urine increased the risk of developing uroepithelial cytogenotoxicity.

PMID- 20798029
TI  - A graphical tool to evaluate temporal coverage of occupational history by
      exposure measurements.
AB  - INTRODUCTION: In occupational epidemiology, differences in the temporal coverage
      of the exposure history by available exposure measurement data may affect the
      uncertainty of exposure estimates. In the reporting of results of studies,
      greater attention should be paid to the extent to which exposure assessments
      require extrapolation outside the timeframe for which exposure measurements are
      available. We propose a simple graphical method that can be used to visualise the
      temporal coverage of exposure history with exposure measurements and the extent
      of temporal extrapolation needed. METHODS: We construct a graph that displays the
      accumulated work history years for which exposure had to be assessed in each
      calendar year. Years for which exposure measurements were available are shaded.
      The proportion of work history years covered by exposure measurements and the
      proportion of work history years accrued before the first measurements are
      summarised. When available, the actual number of measurements available in each
      calendar year is shown. RESULTS: We demonstrate the application of the graphical
      tool in three nested case-control studies that reported on leukaemia in relation
      to low-level benzene exposures in the petroleum industry. Considerable
      differences in temporal coverage between the studies were illustrated, which may
      have resulted in differences in the reliability of the retrospective exposure
      estimates derived for these studies. CONCLUSION: We introduce a graphical tool
      for visualising the temporal coverage by available exposure measurement data in
      epidemiological studies and encourage others to use similar graphs to derive and
      share better qualitative insights into the uncertainty in exposure assessment.

PMID- 20798030
TI  - Return-to-work interventions integrated into cancer care: a systematic review.
AB  - OBJECTIVES: The purpose of this study was to review the literature on the content
      of interventions focusing on return to work, employment status, or work retention
      in patients with cancer. Furthermore, the effect of the interventions on return
      to work was assessed in studies reporting return to work. METHODS: A literature
      search was conducted using the databases MEDLINE, PsycINFO, EMBASE and CINAHL.
      Articles that described a work-directed intervention focusing on return to work,
      employment status, or work retention in patients with cancer were included. The
      content of the work-directed part of the interventions was assessed based on two
      criteria for content analysis: 1. does the setting fit the shared care model of
      cancer survivor care? 2. Does the intervention target work ability and physical
      workload? For studies reporting return-to-work outcomes, the return-to-work rates
      were assessed. For studies that used a control group the ORs and the 95% CIs were
      calculated. RESULTS: Twenty-three articles describing 19 interventions met the
      inclusion criteria. Seven studies reported return-to-work outcomes of which four
      used a control group. Only three interventions aimed primarily at enhancing
      return to work or employment status. The most frequently reported work-directed
      components were encouragement, education or advice about work or work-related
      subjects (68%), vocational or occupational training (21%), or work accommodations
      (11%). One intervention fit the shared care model of cancer survivor care and
      five interventions enhanced work ability or decreased physical workload. The rate
      of return to work ranged from 37% to 89%. In one of the four controlled studies
      the intervention increased return to work significantly and in the other studies
      the results were insignificant. CONCLUSIONS: Only few interventions are primarily
      aimed at enhancing return to work in patients with cancer and most do not fit the
      shared care model involving integrated cancer care. Future studies should be
      developed with well-structured work-directed components that should be evaluated
      in randomised controlled trials.

PMID- 20798031
TI  - AMPA receptors gate spine Ca(2+) transients and spike-timing-dependent
      potentiation.
AB  - Spike timing-dependent long-term potentiation (t-LTP) is the embodiment of Donald
      Hebb's postulated rule for associative memory formation. Pre- and postsynaptic
      action potentials need to be precisely correlated in time to induce this form of
      synaptic plasticity. NMDA receptors have been proposed to detect correlated
      activity and to trigger synaptic plasticity. However, the slow kinetic of NMDA
      receptor currents is at odds with the millisecond precision of coincidence
      detection. Here we show that AMPA receptors are responsible for the extremely
      narrow time window for t-LTP induction. Furthermore, we visualized synergistic
      interactions between AMPA and NMDA receptors and back-propagating action
      potentials on the level of individual spines. Supralinear calcium signals were
      observed for spike timings that induced t-LTP and were most pronounced in spines
      well isolated from the dendrite. We conclude that AMPA receptors gate the
      induction of associative synaptic plasticity by regulating the temporal precision
      of coincidence detection.

PMID- 20798032
TI  - Fine-tuning of neuronal architecture requires two profilin isoforms.
AB  - Two profilin isoforms (PFN1 and PFN2a) are expressed in the mammalian brain.
      Although profilins are essential for regulating actin dynamics in general, the
      specific role of these isoforms in neurons has remained elusive. We show that
      knockdown of the neuron-specific PFN2a results in a significant reduction in
      dendrite complexity and spine numbers of hippocampal neurons. Overexpression of
      PFN1 in PFN2a-deficient neurons prevents the loss of spines but does not restore
      dendritic complexity. Furthermore, we show that profilins are involved in
      differentially regulating actin dynamics downstream of the pan-neurotrophin
      receptor (p75(NTR)), a receptor engaged in modulating neuronal morphology.
      Overexpression of PFN2a restores the morphological changes in dendrites caused by
      p75(NTR) overexpression, whereas PFN1 restores the normal spine density. Our data
      assign specific functions to the two PFN isoforms, possibly attributable to
      different affinities for potent effectors also involved in actin dynamics, and
      suggest that they are important for the signal-dependent fine-tuning of neuronal
      architecture.

PMID- 20798033
TI  - 12/15-lipoxygenase-derived lipid peroxides control receptor tyrosine kinase
      signaling through oxidation of protein tyrosine phosphatases.
AB  - Protein tyrosine phosphatases (PTPs) are regulated through reversible oxidation
      of the active-site cysteine. Previous studies have implied soluble reactive
      oxygen species (ROS), like H(2)O(2), as the mediators of PTP oxidation. The
      potential role(s) of peroxidized lipids in PTP oxidation have not been described.
      This study demonstrates that increases in cellular lipid peroxides, induced by
      disruption of glutathione peroxidase 4, induce cellular PTP oxidation and reduce
      the activity of PDGF receptor targeting PTPs. These effects were accompanied by
      site-selective increased PDGF beta-receptor phosphorylation, sensitive to 12/15
      lipoxygenase (12/15-LOX) inhibitors, and increased PDGF-induced cytoskeletal
      rearrangements. Importantly, the 12/15-LOX-derived 15-OOH-eicosatetraenoic acid
      lipid peroxide was much more effective than H(2)O(2) in induction of in vitro PTP
      oxidation. Our study thus establishes that lipid peroxides are previously
      unrecognized inducers of oxidation of PTPs. This identifies a pathway for control
      of receptor tyrosine kinase signaling, which might also be involved in the
      etiology of diseases associated with increased lipid peroxidation.

PMID- 20798034
TI  - Differentiated Parkinson patient-derived induced pluripotent stem cells grow in
      the adult rodent brain and reduce motor asymmetry in Parkinsonian rats.
AB  - Recent advances in deriving induced pluripotent stem (iPS) cells from patients
      offer new possibilities for biomedical research and clinical applications, as
      these cells could be used for autologous transplantation. We differentiated iPS
      cells from patients with Parkinson's disease (PD) into dopaminergic (DA) neurons
      and show that these DA neurons can be transplanted without signs of
      neurodegeneration into the adult rodent striatum. The PD patient iPS (PDiPS) cell
      derived DA neurons survived at high numbers, showed arborization, and mediated
      functional effects in an animal model of PD as determined by reduction of
      amphetamine- and apomorphine-induced rotational asymmetry, but only a few DA
      neurons projected into the host striatum at 16 wk after transplantation. We next
      applied FACS for the neural cell adhesion molecule NCAM on differentiated PDiPS
      cells before transplantation, which resulted in surviving DA neurons with
      functional effects on amphetamine-induced rotational asymmetry in a 6-OHDA animal
      model of PD. Morphologically, we found that PDiPS cell-derived non-DA neurons
      send axons along white matter tracts into specific close and remote gray matter
      target areas in the adult brain. Such findings establish the transplantation of
      human PDiPS cell-derived neurons as a long-term in vivo method to analyze
      potential disease-related changes in a physiological context. Our data also
      demonstrate proof of principle of survival and functional effects of PDiPS cell
      derived DA neurons in an animal model of PD and encourage further development of
      differentiation protocols to enhance growth and function of implanted PDiPS cell
      derived DA neurons in regard to potential therapeutic applications.

PMID- 20798035
TI  - Defective membrane expression of the Na(+)-HCO(3)(-) cotransporter NBCe1 is
      associated with familial migraine.
AB  - Homozygous mutations in SLC4A4, encoding the electrogenic Na(+)-HCO(3)(-)
      cotransporter NBCe1, have been known to cause proximal renal tubular acidosis
      (pRTA) and ocular abnormalities. In this study, we report two sisters with pRTA,
      ocular abnormalities, and hemiplegic migraine. Genetic analysis ruled out
      pathological mutations in the known genes for familial hemiplegic migraine, but
      identified a homozygous 65-bp deletion (Delta65bp) in the C terminus of NBCe1,
      corresponding to the codon change S982NfsX4. Several heterozygous members of this
      family also presented glaucoma and migraine with or without aura. Despite the
      normal electrogenic activity in Xenopus oocytes, the Delta65bp mutant showed
      almost no transport activity due to a predominant cytosolic retention in
      mammalian cells. Furthermore, coexpression experiments uncovered a dominant
      negative effect of the mutant through hetero-oligomer formation with wild-type
      NBCe1. Among other pRTA pedigrees with different NBCe1 mutations, we identified
      four additional homozygous patients with migraine. The immunohistological and
      functional analyses of these mutants demonstrate that the near total loss of
      NBCe1 activity in astrocytes can cause migraine potentially through dysregulation
      of synaptic pH.

PMID- 20798036
TI  - Mouse retroviruses and chronic fatigue syndrome: Does X (or P) mark the spot?

PMID- 20798037
TI  - Epigenetic effects of polymorphic Y chromosomes modulate chromatin components,
      immune response, and sexual conflict.
AB  - Genetic conflicts between sexes and generations provide a foundation for
      understanding the functional evolution of sex chromosomes and sexually dimorphic
      phenotypes. Y chromosomes of Drosophila contain multi-megabase stretches of
      satellite DNA repeats and a handful of protein-coding genes that are monomorphic
      within species. Nevertheless, polymorphic variation in heterochromatic Y
      chromosomes of Drosophila result in genome-wide gene expression variation. Here
      we show that such naturally occurring Y-linked regulatory variation (YRV) can be
      detected in somatic tissues and contributes to the epigenetic balance of
      heterochromatin/euchromatin at three distinct loci showing position-effect
      variegation (PEV). Moreover, polymorphic Y chromosomes differentially affect the
      expression of thousands of genes in XXY female genotypes in which Y-linked
      protein-coding genes are not transcribed. The data show a disproportionate
      influence of YRV on the variable expression of genes whose protein products
      localize to the nucleus, have nucleic-acid binding activity, and are involved in
      transcription, chromosome organization, and chromatin assembly. These include key
      components such as HP1, Trithorax-like (GAGA factor), Su(var)3-9, Brahma, MCM2,
      ORC2, and inner centromere protein. Furthermore, mitochondria-related genes,
      immune response genes, and transposable elements are also disproportionally
      affected by Y chromosome polymorphism. These functional clusterings may arise as
      a consequence of the involvement of Y-linked heterochromatin in the origin and
      resolution of genetic conflicts between males and females. Taken together, our
      results indicate that Y chromosome heterochromatin serves as a major source of
      epigenetic variation in natural populations that interacts with chromatin
      components to modulate the expression of biologically relevant phenotypic
      variation.

PMID- 20798038
TI  - Disruption of HDAC/CoREST/REST repressor by dnREST reduces genome silencing and
      increases virulence of herpes simplex virus.
AB  - In nonneuronal cells, herpes simplex virus 1 overcomes host defenses, replicates,
      and ultimately kills the infected cell. Among the host defenses suppressed by the
      virus is a repressor complex whose key components are histone deacetylase (HDAC)
      1 or 2, RE-1 silencing transcription factor (REST), corepressor of REST (CoREST),
      and lysine-specific demethylase (LSD) 1. In neurons innervating cells at the
      portal of entry into the body, the virus establishes a "latent" infection in
      which viral DNA is silenced with the exception of a family of genes. The question
      posed here is whether the virus hijacks this repressor complex to silence itself
      in neurons during the latent state. To test this hypothesis, we inserted into the
      wild-type virus genome a wild-type REST [recombinant (R) 111], a dominant
      negative REST (dnREST) lacking the N- and C-terminal repressor domains (R112), or
      an insertion control consisting of tandem repeats of stop codons (R113). The
      recombinant virus R112 carrying the dnREST replicated better and was more
      virulent than the wild-type parent or the other recombinant viruses when
      administered by the corneal or i.p. routes. Moreover, in contrast to other
      recombinants, corneal route inoculation by R112 recombinant virus resulted in
      higher DNA copy numbers, higher levels of infectious virus in eye, trigeminal
      ganglion, or brain, and virtually complete destruction of trigeminal ganglia in
      mice that may ultimately succumb to infection. These results support an earlier
      conclusion that the HDAC/CoREST/REST/LSD1 repressor complex is a significant
      component of the host innate immunity and are consistent with the hypothesis that
      HSV-1 hijacks the repressor to silence itself during latent infection.

PMID- 20798039
TI  - Noninvasive method for assessing the human circadian clock using hair follicle
      cells.
AB  - A thorough understanding of the circadian clock requires qualitative evaluation
      of circadian clock gene expression. Thus far, no simple and effective method for
      detecting human clock gene expression has become available. This limitation has
      greatly hampered our understanding of human circadian rhythm. Here we report a
      convenient, reliable, and less invasive method for detecting human clock gene
      expression using biopsy samples of hair follicle cells from the head or chin. We
      show that the circadian phase of clock gene expression in hair follicle cells
      accurately reflects that of individual behavioral rhythms, demonstrating that
      this strategy is appropriate for evaluating the human peripheral circadian clock.
      Furthermore, using this method, we indicate that rotating shift workers suffer
      from a serious time lag between circadian gene expression rhythms and lifestyle.
      Qualitative evaluation of clock gene expression in hair follicle cells,
      therefore, may be an effective approach for studying the human circadian clock in
      the clinical setting.

PMID- 20798040
TI  - Hyper telomere recombination accelerates replicative senescence and may promote
      premature aging.
AB  - Werner syndrome and Bloom syndrome result from defects in the RecQ helicases
      Werner (WRN) and Bloom (BLM), respectively, and display premature aging
      phenotypes. Similarly, XFE progeroid syndrome results from defects in the ERCC1
      XPF DNA repair endonuclease. To gain insight into the origin of cellular
      senescence and human aging, we analyzed the dependence of sister chromatid
      exchange (SCE) frequencies on location [i.e., genomic (G-SCE) vs. telomeric (T
      SCE) DNA] in primary human fibroblasts deficient in WRN, BLM, or ERCC1-XPF.
      Consistent with our other studies, we found evidence of elevated T-SCE in
      telomerase-negative but not telomerase-positive backgrounds. In telomerase
      negative WRN-deficient cells, T-SCE-but not G-SCE-frequencies were significantly
      increased compared with controls. In contrast, SCE frequencies were significantly
      elevated in BLM-deficient cells irrespective of genome location. In ERCC1-XPF
      deficient cells, neither T- nor G-SCE frequencies differed from controls. A
      theoretical model was developed that allowed an in silico investigation into the
      cellular consequences of increased T-SCE frequency. The model predicts that in
      cells with increased T-SCE, the onset of replicative senescence is dramatically
      accelerated even though the average rate of telomere loss has not changed.
      Premature cellular senescence may act as a powerful tumor-suppressor mechanism in
      telomerase-deficient cells with mutations that cause T-SCE levels to rise.
      Furthermore, T-SCE-driven premature cellular senescence may be a factor
      contributing to accelerated aging in Werner and Bloom syndromes, but not XFE
      progeroid syndrome.

PMID- 20798041
TI  - Conserved RNaseII domain protein functions in cytoplasmic mRNA decay and
      suppresses Arabidopsis decapping mutant phenotypes.
AB  - Both transcription and RNA decay are critical for normal gene regulation.
      Arabidopsis mutants with defects in VARICOSE (VCS), a decapping complex scaffold
      protein, lack mRNA decapping and 5'-to-3' decay. These mutants show either severe
      or suppressed phenotypes, depending on the Arabidopsis accession. Here, we show
      that the molecular basis for this variation is the SUPPRESSOR OF VARICOSE (SOV),
      a locus that encodes a conserved, cytoplasmically localized RRP44-like RNaseII
      domain protein. In vivo RNA decay assays suggest that active forms of this
      protein carry out decay on mRNA substrates that overlap with those of the
      decapping complex. Members of this conserved gene family encode proteins lacking
      the PIN domain, suggesting that SOV is not a functional component of the RNA
      exosome.

PMID- 20798042
TI  - Patients, patience, and the publication process.

PMID- 20798043
TI  - Extracellular DNA traps promote thrombosis.
AB  - Neutrophil extracellular traps (NETs) are part of the innate immune response to
      infections. NETs are a meshwork of DNA fibers comprising histones and
      antimicrobial proteins. Microbes are immobilized in NETs and encounter a locally
      high and lethal concentration of effector proteins. Recent studies show that NETs
      are formed inside the vasculature in infections and noninfectious diseases. Here
      we report that NETs provide a heretofore unrecognized scaffold and stimulus for
      thrombus formation. NETs perfused with blood caused platelet adhesion,
      activation, and aggregation. DNase or the anticoagulant heparin dismantled the
      NET scaffold and prevented thrombus formation. Stimulation of platelets with
      purified histones was sufficient for aggregation. NETs recruited red blood cells,
      promoted fibrin deposition, and induced a red thrombus, such as that found in
      veins. Markers of extracellular DNA traps were detected in a thrombus and plasma
      of baboons subjected to deep vein thrombosis, an example of inflammation-enhanced
      thrombosis. Our observations indicate that NETs are a previously unrecognized
      link between inflammation and thrombosis and may further explain the
      epidemiological association of infection with thrombosis.

PMID- 20798044
TI  - Angiotensin-converting enzyme 2 attenuates atherosclerotic lesions by targeting
      vascular cells.
AB  - Angiotensin-converting enzyme 2 (ACE2) is a newly discovered homolog of ACE whose
      actions oppose those of angiotensin II (AngII). However, the underlying
      mechanisms by which ACE2 effectively suppresses early atherosclerotic lesions
      remain poorly understood. Here, we show, both in vitro and in vivo, that ACE2
      inhibited the development of early atherosclerotic lesions by suppressing the
      growth of vascular smooth muscle cells (VSMCs) and improving endothelial
      function. In a relatively large cohort animal study (66 rabbits), aortic segments
      transfected by Ad-ACE2 showed significantly attenuated fatty streak formation,
      neointimal macrophage infiltration, and alleviation of impaired endothelial
      function. Segments also showed decreased expression of monocyte chemoattractant
      protein 1, lectin-like oxidized low-density lipoprotein receptor 1, and
      proliferating cell nuclear antigen, which led to the delayed onset of
      atherosclerotic lesions. At the cellular level, ACE2 significantly modulated
      AngII-induced growth and migration in human umbilical vein endothelial cells and
      VSMCs. The antiatherosclerotic effect of ACE2 involved down-regulation of the ERK
      p38, JAK-STAT, and AngII-ROS-NF-kappaB signaling pathways and up-regulation of
      the PI3K-Akt pathway. These findings revealed the molecular mechanisms of the
      antiatherosclerotic activity of ACE2 and suggested that modulation of ACE2 could
      offer a therapeutic option for treating atherosclerosis.

PMID- 20798045
TI  - Ezh2, the histone methyltransferase of PRC2, regulates the balance between self
      renewal and differentiation in the cerebral cortex.
AB  - Multipotent progenitor cells of the cerebral cortex balance self-renewal and
      differentiation to produce complex neural lineages in a fixed temporal order in a
      cell-autonomous manner. We studied the role of the polycomb epigenetic system, a
      chromatin-based repressive mechanism, in controlling cortical progenitor cell
      self-renewal and differentiation. We found that the histone methyltransferase of
      polycomb repressive complex 2 (PCR2), enhancer of Zeste homolog 2 (Ezh2), is
      essential for controlling the rate at which development progresses within
      cortical progenitor cell lineages. Loss of function of Ezh2 removes the
      repressive mark of trimethylated histone H3 at lysine 27 (H3K27me3) in cortical
      progenitor cells and also prevents its establishment in postmitotic neurons.
      Removal of this repressive chromatin modification results in marked up-regulation
      in gene expression, the consequence of which is a shift in the balance between
      self-renewal and differentiation toward differentiation, both directly to neurons
      and indirectly via basal progenitor cell genesis. Although the temporal order of
      neurogenesis and gliogenesis are broadly conserved under these conditions, the
      timing of neurogenesis, the relative numbers of different cell types, and the
      switch to gliogenesis are all altered, narrowing the neurogenic period for
      progenitor cells and reducing their neuronal output. As a consequence, the timing
      of cortical development is altered significantly after loss of PRC2 function.

PMID- 20798046
TI  - Notch signaling specifies prosensory domains via lateral induction in the
      developing mammalian inner ear.
AB  - During inner ear morphogenesis, the process of prosensory specification defines
      the specific regions of the otic epithelium that will give rise to the six
      separate inner ear organs essential for hearing and balance. The mechanism of
      prosensory specification is not fully understood, but there is evidence that the
      Notch intercellular signaling pathway plays a critical role. The Notch ligand
      Jagged1 (Jag1) is expressed in the prosensory domains, and mutation of Jag1
      impairs sensory formation. Furthermore, pharmacological inhibition of Notch in
      vitro during prosensory specification disrupts the prosensory process.
      Additionally, activation of Notch by cDNA electroporation in chick otocysts
      results in formation of ectopic sensory patches. Here we test whether Notch
      activity is sufficient for prosensory specification in the mouse, using a Cre
      /loxP approach to conditionally activate the Notch pathway in nonsensory regions
      of the inner ear epithelia during different stages of otic vesicle morphogenesis.
      We find that broad ectopic activation of Notch at very early developmental stages
      causes induction of prosensory markers throughout the entire otic epithelium. At
      later stages of development, activation of Notch in nonsensory regions leads to
      induction of sensory patches that later differentiate to form complete ectopic
      sensory structures. Activation of Notch in isolated nonsensory cells results in
      lateral induction of Jag1 expression in neighboring cells and spreading of
      prosensory specification to the adjacent cells through an intercellular
      mechanism. These results support a model where activation of Notch and
      propagation through lateral induction promote prosensory character in specific
      regions of the developing otocyst.

PMID- 20798047
TI  - Detection of MLV-related virus gene sequences in blood of patients with chronic
      fatigue syndrome and healthy blood donors.
AB  - Chronic fatigue syndrome (CFS) is a serious systemic illness of unknown cause. A
      recent study identified DNA from a xenotropic murine leukemia virus-related virus
      (XMRV) in peripheral blood mononuclear cells (PBMCs) from 68 of 101 patients
      (67%) by nested PCR, as compared with 8 of 218 (3.7%) healthy controls. However,
      four subsequent reports failed to detect any murine leukemia virus (MLV)-related
      virus gene sequences in blood of CFS patients. We examined 41 PBMC-derived DNA
      samples from 37 patients meeting accepted diagnostic criteria for CFS and found
      MLV-like virus gag gene sequences in 32 of 37 (86.5%) compared with only 3 of 44
      (6.8%) healthy volunteer blood donors. No evidence of mouse DNA contamination was
      detected in the PCR assay system or the clinical samples. Seven of 8 gag-positive
      patients tested again positive in a sample obtained nearly 15 y later. In
      contrast to the reported findings of near-genetic identity of all XMRVs, we
      identified a genetically diverse group of MLV-related viruses. The gag and env
      sequences from CFS patients were more closely related to those of polytropic
      mouse endogenous retroviruses than to those of XMRVs and were even less closely
      related to those of ecotropic MLVs. Further studies are needed to determine
      whether the same strong association with MLV-related viruses is found in other
      groups of patients with CFS, whether these viruses play a causative role in the
      development of CFS, and whether they represent a threat to the blood supply.

PMID- 20798048
TI  - Perceptual learning beyond retinotopic reference frame.
AB  - Repetitive experience with the same visual stimulus and task can remarkably
      improve behavioral performance on the task. This well-known perceptual-learning
      phenomenon is usually specific to the trained retinal- or visual-field location,
      which is taken as an indication of plastic changes in retinotopic visual areas.
      In previous studies of perceptual learning, however, a change in stimulus
      location on the retina is accompanied by positional changes of the stimulus in
      nonretinotopic frames of reference, such as relative to the head and other
      objects. It is unclear, therefore, whether the putative location specificity is
      exclusively retinotopic or if it could also depend on nonretinotopic
      representation of the stimulus, which is particularly important for multisensory
      and sensorimotor integration as well as for maintenance of stable visual
      percepts. Here, by manipulating subjects' gaze direction to control spatial and
      retinal locations of stimuli independently, we found that, when the stimulated
      retinal regions were held constant, the improvement with training in motion
      direction discrimination of two successively displayed stimuli was restricted to
      the relative spatial position of the stimuli but independent of their absolute
      locations in head- and world-centered frame. These findings indicate location
      specificity of perceptual learning beyond retinotopic frame of reference,
      suggesting a pliable spatiotopic mechanism that can be specifically shaped by
      experience for better spatiotemporal integration of the learned stimuli.

PMID- 20798049
TI  - The apical-basal cell polarity determinant Crumbs regulates Hippo signaling in
      Drosophila.
AB  - Defects in apical-basal cell polarity and abnormal expression of cell polarity
      determinants are often associated with cancer in vertebrates. In Drosophila,
      abnormal expression of apical-basal determinants can cause neoplastic phenotypes,
      including loss of cell polarity and overproliferation. However, the pathways
      through which apical-basal polarity determinants affect growth are poorly
      understood. Here, we investigated the mechanism by which the apical determinant
      Crumbs (Crb) affects growth in Drosophila imaginal discs. Overexpression of Crb
      causes severe overproliferation, and we found that loss of Crb similarly results
      in overgrowth of imaginal discs. Crb gain and loss of function caused defects in
      Hippo signaling, a key signaling pathway that controls tissue growth in
      Drosophila and mammals. Manipulation of Crb levels caused the up-regulation of
      Hippo target genes, genetically interacted with known Hippo pathway components,
      and required Yorkie, a transcriptional coactivator that acts downstream in the
      Hippo pathway, for target gene induction and overgrowth. Interestingly, Crb
      regulates growth and cell polarity through different motifs in its intracellular
      domain. A juxtamembrane FERM domain-binding motif is responsible for growth
      regulation and induction of Hippo target gene expression, whereas Crb uses a PDZ
      binding motif to form a complex with other polarity factors. The Hippo pathway
      component Expanded, an apically localized adaptor protein, is mislocalized in
      both crb mutant cells and Crb overexpressing tissues, whereas the other Hippo
      pathway components, Fat and Merlin, are unaffected. Taken together, our data show
      that Crb regulates growth through Hippo signaling, and thus identify Crb as a
      previously undescribed upstream input into the Hippo pathway.

PMID- 20798050
TI  - Neuron densities vary across and within cortical areas in primates.
AB  - The numbers and proportion of neurons in areas and regions of cortex were
      determined for a single cortical hemisphere from two prosimian galagos, one New
      World owl monkey, one Old World macaque monkey, and one baboon. The results
      suggest that there is a common plan of cortical organization across the species
      examined here and also differences that suggest greater specializations in the
      Old World monkeys. In all primates examined, primary visual cortex (V1) was the
      most neuron-dense cortical area and the secondary visual areas had higher-than
      average densities. Primary auditory and somatosensory areas tended to have high
      densities in the Old World macaque and baboon. Neuronal density varies less
      across cortical areas in prosimian galagos than in the Old World monkeys. Thus,
      cortical architecture varies greatly within and across primate species, but cell
      density is greater in cortex devoted to the early stages of sensory processing.

PMID- 20798051
TI  - FGF receptor-4 (FGFR4) polymorphism acts as an activity switch of a membrane type
      1 matrix metalloproteinase-FGFR4 complex.
AB  - Tumor cells use membrane type 1 matrix metalloproteinase (MT1-MMP) for invasion
      and metastasis. However, the signaling mechanisms that underlie MT1-MMP
      regulation in cancer have remained unclear. Using a systematic gain-of-function
      kinome screen for MT1-MMP activity, we have here identified kinases that
      significantly enhance MT1-MMP activity in tumor cells. In particular, we
      discovered an MT1-MMP/FGF receptor-4 (FGFR4) membrane complex that either
      stimulates or suppresses MT1-MMP and FGFR4 activities, depending on a tumor
      progression-associated polymorphism in FGFR4. The FGFR4-R388 allele, linked to
      poor cancer prognosis, increased collagen invasion by decreasing lysosomal MT1
      MMP degradation. FGFR4-R388 induced MT1-MMP phosphorylation and endosomal
      stabilization, and surprisingly, the increased MT1-MMP in return enhanced FGFR4
      R388 autophosphorylation. A phosphorylation-defective MT1-MMP was stabilized on
      the cell surface, where it induced simultaneous FGFR4-R388 internalization and
      dissociation of cell-cell junctions. In contrast, the alternative FGFR4-G388
      variant down-regulated MT1-MMP, and the overexpression of MT1-MMP and
      particularly its phosphorylation-defective mutant vice versa induced FGFR4-G388
      degradation. These results provide a mechanistic basis for FGFR4-R388 function in
      cancer invasion.

PMID- 20798052
TI  - Adaptor protein is essential for insect cytokine signaling in hemocytes.
AB  - Growth-blocking peptide (GBP) is an insect cytokine that stimulates a class of
      immune cells called plasmatocytes to adhere to one another and to foreign
      surfaces. Although extensive structure-activity studies have been performed on
      the GBP and its mutants in Lepidoptera Pseudaletia separata, the signaling
      pathway of GBP-dependent activation of plasmatocytes remains unknown. We
      identified an adaptor protein (P77) with a molecular mass of 77 kDa containing
      SH2/SH3 domain binding motifs and an immunoreceptor tyrosine-based activation
      motif (ITAM)-like domain in the cytoplasmic region of the C terminus. Although
      P77 showed no capacity for direct binding with GBP, its cytoplasmic tyrosine
      residues were specifically phosphorylated within seconds after GBP was added to a
      plasmatocyte suspension. Tyrosine phosphorylation of P77 also was observed when
      hemocytes were incubated with Enterobactor cloacae or Micrococcus luteus, but
      this phosphorylation was found to be induced by GBP released from hemocytes
      stimulated by the pathogens. Tyrosine phosphorylation of the integrin beta
      subunit also was detected in plasmatocytes stimulated by GBP. Double-stranded
      RNAs targeting P77 not only decreased GBP-dependent tyrosine phosphorylation of
      the integrin beta subunit, but also abolished GBP-induced spreading of
      plasmatocytes on foreign surfaces. P77 RNAi larvae also showed significantly
      higher mortality than control larvae after infection with Serratia marcescens,
      indicating that P77 is essential for GBP to mediate a normal innate cellular
      immunity in insects. These results demonstrate that GBP signaling in
      plasmatocytes requires the adaptor protein P77, and that active P77-assisted
      tyrosine phosphorylation of integrins is critical for the activation of
      plasmatocytes.

PMID- 20798053
TI  - Metallic ferromagnetism in the Kondo lattice.
AB  - Metallic magnetism is both ancient and modern, occurring in such familiar
      settings as the lodestone in compass needles and the hard drive in computers.
      Surprisingly, a rigorous theoretical basis for metallic ferromagnetism is still
      largely missing. The Stoner approach perturbatively treats Coulomb interactions
      when the latter need to be large, whereas the Nagaoka approach incorporates
      thermodynamically negligible holes into a half-filled band. Here, we show that
      the ferromagnetic order of the Kondo lattice is amenable to an asymptotically
      exact analysis over a range of interaction parameters. In this ferromagnetic
      phase, the conduction electrons and local moments are strongly coupled but the
      Fermi surface does not enclose the latter (i.e., it is "small"). Moreover, non
      Fermi-liquid behavior appears over a range of frequencies and temperatures. Our
      results provide the basis to understand some long-standing puzzles in the
      ferromagnetic heavy fermion metals, and raise the prospect for a new class of
      ferromagnetic quantum phase transitions.

PMID- 20798054
TI  - Four-electron oxidation of p-hydroxylaminobenzoate to p-nitrobenzoate by a
      peroxodiferric complex in AurF from Streptomyces thioluteus.
AB  - The nonheme di-iron oxygenase, AurF, converts p-aminobenzoate (Ar-NH(2), where Ar
      = 4-carboxyphenyl) to p-nitrobenzoate (Ar-NO(2)) in the biosynthesis of the
      antibiotic, aureothin, by Streptomyces thioluteus. It has been reported that this
      net six-electron oxidation proceeds in three consecutive, two-electron steps,
      through p-hydroxylaminobenzoate (Ar-NHOH) and p-nitrosobenzoate (Ar-NO)
      intermediates, with each step requiring one equivalent of O(2) and two exogenous
      reducing equivalents. We recently demonstrated that a peroxodiiron(III/III)
      complex (peroxo- -AurF) formed by addition of O(2) to the diiron(II/II) enzyme ( 
      AurF) effects the initial oxidation of Ar-NH(2), generating a mu
      (oxo)diiron(III/III) form of the enzyme (mu-oxo- -AurF) and (presumably) Ar-NHOH.
      Here we show that peroxo- -AurF also oxidizes Ar-NHOH. Unexpectedly, this
      reaction proceeds through to the Ar-NO(2) final product, a four-electron
      oxidation, and produces -AurF, with which O(2) can combine to regenerate peroxo- 
      AurF. Thus, conversion of Ar-NHOH to Ar-NO(2) requires only a single equivalent
      of O(2) and (starting from -AurF or peroxo- -AurF) is fully catalytic in the
      absence of exogenous reducing equivalents, by contrast to the published
      stoichiometry. This novel type of four-electron N-oxidation is likely also to
      occur in the reaction sequences of nitro-installing di-iron amine oxygenases in
      the biosyntheses of other natural products.

PMID- 20798055
TI  - Efficacy of geoengineering to limit 21st century sea-level rise.
AB  - Geoengineering has been proposed as a feasible way of mitigating anthropogenic
      climate change, especially increasing global temperatures in the 21st century.
      The two main geoengineering options are limiting incoming solar radiation, or
      modifying the carbon cycle. Here we examine the impact of five geoengineering
      approaches on sea level; SO(2) aerosol injection into the stratosphere, mirrors
      in space, afforestation, biochar, and bioenergy with carbon sequestration. Sea
      level responds mainly at centennial time scales to temperature change, and has
      been largely driven by anthropogenic forcing since 1850. Making use a model of
      sea-level rise as a function of time-varying climate forcing factors (solar
      radiation, volcanism, and greenhouse gas emissions) we find that sea-level rise
      by 2100 will likely be 30 cm higher than 2000 levels despite all but the most
      aggressive geoengineering under all except the most stringent greenhouse gas
      emissions scenarios. The least risky and most desirable way of limiting sea-level
      rise is bioenergy with carbon sequestration. However aerosol injection or a space
      mirror system reducing insolation at an accelerating rate of 1 W m(-2) per decade
      from now to 2100 could limit or reduce sea levels. Aerosol injection delivering a
      constant 4 W m(-2) reduction in radiative forcing (similar to a 1991 Pinatubo
      eruption every 18 months) could delay sea-level rise by 40-80 years. Aerosol
      injection appears to fail cost-benefit analysis unless it can be maintained
      continuously, and damage caused by the climate response to the aerosols is less
      than about 0.6% Global World Product.

PMID- 20798056
TI  - H-NS forms a superhelical protein scaffold for DNA condensation.
AB  - The histone-like nucleoid structuring (H-NS) protein plays a fundamental role in
      DNA condensation and is a key regulator of enterobacterial gene expression in
      response to changes in osmolarity, pH, and temperature. The protein is capable of
      high-order self-association via interactions of its oligomerization domain. Using
      crystallography, we have solved the structure of this complete domain in an
      oligomerized state. The observed superhelical structure establishes a mechanism
      for the self-association of H-NS via both an N-terminal antiparallel coiled-coil
      and a second, hitherto unidentified, helix-turn-helix dimerization interface at
      the C-terminal end of the oligomerization domain. The helical scaffold suggests
      the formation of a H-NS:plectonemic DNA nucleoprotein complex that is capable of
      explaining published biophysical and functional data, and establishes a unifying
      structural basis for coordinating the DNA packaging and transcription repression
      functions of H-NS.

PMID- 20798057
TI  - RNA polymerase II trigger loop residues stabilize and position the incoming
      nucleotide triphosphate in transcription.
AB  - A structurally conserved element, the trigger loop, has been suggested to play a
      key role in substrate selection and catalysis of RNA polymerase II (pol II)
      transcription elongation. Recently resolved X-ray structures showed that the
      trigger loop forms direct interactions with the beta-phosphate and base of the
      matched nucleotide triphosphate (NTP) through residues His1085 and Leu1081,
      respectively. In order to understand the role of these two critical residues in
      stabilizing active site conformation in the dynamic complex, we performed all
      atom molecular dynamics simulations of the wild-type pol II elongation complex
      and its mutants in explicit solvent. In the wild-type complex, we found that the
      trigger loop is stabilized in the "closed" conformation, and His1085 forms a
      stable interaction with the NTP. Simulations of point mutations of His1085 are
      shown to affect this interaction; simulations of alternative protonation states,
      which are inaccessible through experiment, indicate that only the protonated form
      is able to stabilize the His1085-NTP interaction. Another trigger loop residue,
      Leu1081, stabilizes the incoming nucleotide position through interaction with the
      nucleotide base. Our simulations of this Leu mutant suggest a three-component
      mechanism for correctly positioning the incoming NTP in which (i) hydrophobic
      contact through Leu1081, (ii) base stacking, and (iii) base pairing work together
      to minimize the motion of the incoming NTP base. These results complement
      experimental observations and provide insight into the role of the trigger loop
      on transcription fidelity.

PMID- 20798058
TI  - Imprinting self-assembled patterns of lines at a semiconductor surface, using
      heat, light, or electrons.
AB  - The fabrication of nano devices at surfaces makes conflicting demands of mobility
      for self-assembly (SA) and immobility for permanence. The solution proposed in
      earlier work from this laboratory involved pattern formation in physisorbed
      molecules by SA, followed by localized reaction to chemically imprint the pattern
      substantially unchanged, a procedure we termed molecular-scale imprinting (MSI).
      Here, as proof of generality we extended this procedure, previously applied to
      imprinting circles on Si(111)-7 * 7, to SA lines of 1-chloropentane (CP) on
      Si(100)-2 * 1. The physisorbed lines consisted of pairs of CP that grew
      perpendicular to the Si dimer rows, as shown by scanning tunneling microscopy and
      ab initio theory. Chemical reaction of these lines with the surface was triggered
      in separate experiments by three different modes of energization: heat,
      electrons, or light. In all cases the CP molecules underwent MSI with a Si atom
      beneath so that the physisorbed lines of CP pairs were imprinted as chemisorbed
      lines of Cl pairs.

PMID- 20798059
TI  - Superconductivity at approximately 100 K in dense SiH4(H2)2 predicted by first
      principles.
AB  - Motivated by the potential high-temperature superconductivity in hydrogen-rich
      materials, the high-pressure structures of SiH(4)(H(2))(2) in the pressure range
      50-300 GPa were extensively explored by using a genetic algorithm. An intriguing
      layered orthorhombic (Ccca) structure was revealed to be energetically stable
      above 248 GPa with the inclusion of zero-point energy. The Ccca structure is
      metallic and composed of hydrogen shared SiH(8) dodecahedra layers intercalated
      by orientationally ordered molecular H(2). Application of the Allen-Dynes
      modified McMillan equation yields remarkably high superconducting temperatures of
      98-107 K at 250 GPa, among the highest values reported so far for phonon-mediated
      superconductors. Analysis reveals a unique superconducting mechanism that the
      direct interactions between H(2) and SiH(4) molecules at high pressure play the
      major role in the high superconductivity, while the contribution from H(2)
      vibrons is minor.

PMID- 20798060
TI  - Assembly of Q{beta} viral RNA polymerase with host translational elongation
      factors EF-Tu and -Ts.
AB  - Replication and transcription of viral RNA genomes rely on host-donated proteins.
      Qbeta virus infects Escherichia coli and replicates and transcribes its own
      genomic RNA by Qbeta replicase. Qbeta replicase requires the virus-encoded RNA
      dependent RNA polymerase (beta-subunit), and the host-donated translational
      elongation factors EF-Tu and -Ts, as active core subunits for its RNA
      polymerization activity. Here, we present the crystal structure of the core Qbeta
      replicase, comprising the beta-subunit, EF-Tu and -Ts. The beta-subunit has a
      right-handed structure, and the EF-Tu:Ts binary complex maintains the structure
      of the catalytic core crevasse of the beta-subunit through hydrophobic
      interactions, between the finger and thumb domains of the beta-subunit and domain
      2 of EF-Tu and the coiled-coil motif of EF-Ts, respectively. These hydrophobic
      interactions are required for the expression and assembly of the Qbeta replicase
      complex. Thus, EF-Tu and -Ts have chaperone-like functions in the maintenance of
      the structure of the active Qbeta replicase. Modeling of the template RNA and the
      growing RNA in the catalytic site of the Qbeta replicase structure also suggests
      that structural changes of the RNAs and EF-Tu:Ts should accompany processive RNA
      polymerization and that EF-Tu:Ts in the Qbeta replicase could function to
      modulate the RNA folding and structure.

PMID- 20798061
TI  - Multidomain assembled states of Hck tyrosine kinase in solution.
AB  - An approach combining small-angle X-ray solution scattering (SAXS) data with
      coarse-grained (CG) simulations is developed to characterize the assembly states
      of Hck, a member of the Src-family kinases, under various conditions in solution.
      First, a basis set comprising a small number of assembly states is generated from
      extensive CG simulations. Second, a theoretical SAXS profile for each state in
      the basis set is computed by using the Fast-SAXS method. Finally, the relative
      population of the different assembly states is determined via a Bayesian-based
      Monte Carlo procedure seeking to optimize the theoretical scattering profiles
      against experimental SAXS data. The study establishes the concept of basis-set
      supported SAXS (BSS-SAXS) reconstruction combining computational and experimental
      techniques. Here, BSS-SAXS reconstruction is used to reveal the structural
      organization of Hck in solution and the different shifts in the equilibrium
      population of assembly states upon the binding of different signaling peptides.

PMID- 20798062
TI  - Bioinspired optofluidic FRET lasers via DNA scaffolds.
AB  - Optofluidic dye lasers hold great promise for adaptive photonic devices, compact
      and wavelength-tunable light sources, and micro total analysis systems. To date,
      however, nearly all those lasers are directly excited by tuning the pump laser
      into the gain medium absorption band. Here we demonstrate bioinspired optofluidic
      dye lasers excited by FRET, in which the donor-acceptor distance, ratio, and
      spatial configuration can be precisely controlled by DNA scaffolds. The
      characteristics of the FRET lasers such as spectrum, threshold, and energy
      conversion efficiency are reported. Through DNA scaffolds, nearly 100% energy
      transfer can be maintained regardless of the donor and acceptor concentration. As
      a result, efficient FRET lasing is achieved at an unusually low acceptor
      concentration of micromolar, over 1,000 times lower than that in conventional
      optofluidic dye lasers. The lasing threshold is on the order of MUJ/mm(2).
      Various DNA scaffold FRET lasers are demonstrated to illustrate vast
      possibilities in optofluidic laser designs. Our work opens a door to many
      researches and applications such as intracavity bio/chemical sensing,
      biocontrolled photonic devices, and biophysics.

PMID- 20798063
TI  - Discriminating early stage A{beta}42 monomer structures using chirality-induced
      2DIR spectroscopy in a simulation study.
AB  - Elucidating the structural features of the Abeta monomer, the peptide constituent
      of amyloid fibrils found in Alzheimer's disease, can enable a direct
      characterization of aggregation pathways. Recent studies support the view that
      the ensemble of Abeta42 monomers is a mixture of diverse ordered and disordered
      conformational species, which can be classified according to the formation of a
      characteristic beta-hairpin conformation in a certain region. Despite the
      disparity in the structural features of these species, commonly used
      spectroscopic techniques such as NMR may not directly trace the conformational
      dynamics in the ensemble due to the limited time resolution and the lack of well
      resolved spectral features for different comformers. Here we use molecular
      dynamics simulations combined with simulations of two-dimensional IR (2DIR)
      spectra to investigate the structure of these species, their interchange
      kinetics, and their spectral features. We show that while the discrimination
      efficiency of the ordinary, nonchiral 2DIR signal is limited due to its intrinsic
      dependence on common order parameters that are dominated by the generally
      unstructured part of the sequence, signals with carefully designed chirality
      sensitive pulse configurations have the high resolution required for
      differentiating the various monomer structures. Our combined simulation studies
      indicate the power of the chirality-induced (CI) 2DIR technique in investigating
      early events in Abeta42 aggregation and open the possibility for their use as a
      novel experimental tool.

PMID- 20798064
TI  - Highly sensitive and selective odorant sensor using living cells expressing
      insect olfactory receptors.
AB  - This paper describes a highly sensitive and selective chemical sensor using
      living cells (Xenopus laevis oocytes) within a portable fluidic device. We
      constructed an odorant sensor whose sensitivity is a few parts per billion in
      solution and can simultaneously distinguish different types of chemicals that
      have only a slight difference in double bond isomerism or functional group such
      as -OH, -CHO and -C(=O)-. We developed a semiautomatic method to install cells to
      the fluidic device and achieved stable and reproducible odorant sensing. In
      addition, we found that the sensor worked for multiple-target chemicals and can
      be integrated with a robotic system without any noise reduction systems. Our
      developed sensor is compact and easy to replace in the system. We believe that
      the sensor can potentially be incorporated into a portable system for monitoring
      environmental and physical conditions.

PMID- 20798065
TI  - Functional interactions between membrane-bound transporters and membranes.
AB  - One key role of many cellular membranes is to hold a transmembrane
      electrochemical ion gradient that stores free energy, which is used, for example,
      to generate ATP or to drive transmembrane transport processes. In mitochondria
      and many bacteria, the gradient is maintained by proton-transport proteins that
      are part of the respiratory (electron-transport) chain. Even though our
      understanding of the structure and function of these proteins has increased
      significantly, very little is known about the specific role of functional protein
      membrane and membrane-mediated protein-protein interactions. Here, we have
      investigated the effect of membrane incorporation on proton-transfer reactions
      within the membrane-bound proton pump cytochrome c oxidase. The results show that
      the membrane acts to accelerate proton transfer into the enzyme's catalytic site
      and indicate that the intramolecular proton pathway is wired via specific amino
      acid residues to the two-dimensional space defined by the membrane surface. We
      conclude that the membrane not only acts as a passive barrier insulating the
      interior of the cell from the exterior solution, but also as a component of the
      energy-conversion machinery.

PMID- 20798066
TI  - Screening for human papillomavirus in basaloid squamous carcinoma: utility of
      p16(INK4a), CISH, and PCR.
AB  - This study compares p16( INK4a) immunohistochemistry (IHC), HPV chromogenic in
      situ hybridization (ISH), and HPV polymerase chain reaction (PCR) genotyping for
      detection of HPV infection in basaloid squamous carcinoma (BSCC). A retrospective
      histopathological analysis of 40 BSCC from a single institution was carried out.
      p16 IHC, HPV DNA extraction and ISH, and HPV PCR genotyping were performed, and
      there was excellent agreement between all 3 methods of HPV detection. Analysis of
      variance yielded no significant differences between the results of the 3 tests (
      P = .354) and Pearson product-moment correlation coefficients calculated for each
      pair of tests demonstrated direct correlation (r = .61 for PCR and IHC, r = .61
      for PCR and ISH, and r = 1.00 for ISH and IHC). This supports the use of
      p16(INK4a) IHC as an initial screening tool for HPV infection in BSCC, while
      definitive evidence of HPV DNA can be sought subsequently with PCR or CISH.

PMID- 20798067
TI  - Neuroendocrine-type prostatic adenocarcinoma with microsatellite instability in a
      patient with lynch syndrome.
AB  - Lynch syndrome is an autosomal-dominant cancer syndrome that can be identified
      with microsatellite instability molecular tests or immunohistochemical stains on
      pathologic material from patients who meet the Amsterdam Criteria II. The
      development of prostatic carcinoma in situ or invasive small cell carcinoma (SCC)
      of the prostate has not been previously reported in a patient with this syndrome.
      In this report, an 87-year-old White man with the Lynch syndrome had a prostate
      biopsy that revealed a mixed high-grade conventional adenocarcinoma and SCC of
      the prostate with high-grade prostatic intraepithelial neoplasia of the small
      cell neuroendocrine-type (HGPIN-NE), all showing MSH2 microsatellite instability
      and loss of MSH2 expression, a finding not previously published. These findings
      suggest that HGPIN-NE is a precursor of invasive SCC and also that prostatic SCC
      can develop in a patient with the Lynch syndrome.

PMID- 20798068
TI  - Pneumococcal vaccination process improvement in an acute care setting.
AB  - BACKGROUND AND OBJECTIVE: Despite the availability of the pneumococcal vaccine
      since 1977, the vaccine is greatly underutilised. Centers for Medicare and
      Medicaid Services, The Joint Commission and Healthy People 2010 have all listed
      the administration of the pneumococcal vaccine before hospital discharge as a
      standard of care and a quality initiative in the 21st century. SSM St Mary's
      Health Center chartered a multidisciplinary team to address a disappointing
      pneumococcal vaccination rate of 34.7% in the first quarter of 2005. METHODS: The
      team utilised the improvement model of Plan-Do-Study-Act to implement and monitor
      process changes. Changes were made to four key steps in the pneumococcal
      vaccination process: assessment, ordering, obtaining and administering. The team
      also implemented a concurrent review process. The team tracked the hospital's
      pneumococcal vaccination rate per the published Centers for Medicare and Medicaid
      Services and The Joint Commission guidelines. RESULTS: Over a 2-year period, the
      vaccination rate of pneumonia patients has improved incrementally from 34.7% and
      is now consistently greater than 90%. CONCLUSION: Utilising Plan-Do-Study-Act
      allows for continual improvement of the vaccination process. Multiple cycles are
      necessary to achieve standardisation and optimal process flow.

PMID- 20798069
TI  - Identifying causes of adverse events detected by an automated trigger tool
      through in-depth analysis.
AB  - OBJECTIVES: To describe how in-depth analysis of adverse events can reveal
      underlying causes. METHODS: Triggers for adverse events were developed using the
      hospital's computerised medical record (naloxone for opiate-related oversedation
      and administration of a glucose bolus while on insulin for insulin-related
      hypoglycaemia). Triggers were identified daily. Based on information from the
      medical record and interviews, a subject expert determined if an adverse drug
      event had occurred and then conducted a real-time analysis to identify event
      characteristics. Expert groups, consisting of frontline staff and specialist
      physicians, examined event characteristics and determined the apparent cause.
      RESULTS: 30 insulin-related hypoglycaemia events and 34 opiate-related
      oversedation events were identified by the triggers over 16 and 21 months,
      respectively. In the opinion of the experts, patients receiving continuous
      infusion insulin and those receiving dextrose only via parenteral nutrition were
      at increased risk for insulin-related hypoglycaemia. Lack of standardisation in
      insulin-dosing decisions and variation regarding when and how much to adjust
      insulin doses in response to changing glucose levels were identified as common
      causes of the adverse events. Opiate-related oversedation events often occurred
      within 48 h of surgery. Variation in pain management in the operating room and
      post-anaesthesia care unit was identified by the experts as potential causes.
      Variations in practice, multiple services writing orders, multidrug regimens and
      variations in interpretation of patient assessments were also noted as potential
      contributing causes. CONCLUSIONS: Identification of adverse drug events through
      an automated trigger system, supplemented by in-depth analysis, can help identify
      targets for intervention and improvement.

PMID- 20798070
TI  - Contemporary management of carotid bifurcation atherosclerosis for stroke
      prevention: management options and patient selection.

PMID- 20798071
TI  - The role of carotid revascularization in stroke prevention.
AB  - The goal of carotid disease management is prevention of stroke. Many randomized
      prospective trials of carotid disease management provide level-1 evidence to
      guide decision making to optimize stroke prevention in patients with carotid
      disease. Other patients present with clinical scenarios that fall outside the
      eligibility criteria for these clinical trials, and in these patients, clinical
      decisions must be based on the best available information on the natural history
      of each patient's carotid disease and on the clinician's assessment of the risks
      and benefits of intervention. In this monograph, the author reviews the current
      clinical data relating to carotid revascularization for asymptomatic carotid
      disease, for carotid disease with transient ischemic attack or minor stroke, and
      for carotid disease with acute stroke or stroke in evolution. Relevant clinical
      trials of carotid endarterectomy and carotid stenting are reviewed in detail. In
      addition, relevant natural history and risk-benefit data are reviewed to guide
      clinical decision making in patients whose clinical presentations fall outside
      the scope of the available clinical trials. The goal of this monograph is to
      provide the clinician with an evidence basis for clinical decision making in
      patients with commonly encountered carotid disease-related presentations.

PMID- 20798072
TI  - Commentary on "Role of carotid revascularization in stroke treatment and
      prevention".

PMID- 20798073
TI  - Medical management of carotid stenosis.
AB  - Stroke is a leading cause of morbidity and mortality in the developed world.
      Although the rates of stroke have decreased in North America, there are
      significant areas of risk stratification and management that can be improved.
      Hypertension is the most significant and perhaps most modifiable risk factor for
      stroke. Carotid atherosclerotic disease is associated with 15% of ischemic
      strokes. Although carotid endarterectomy (CEA) remains a recommendation for
      significant symptomatic carotid stenosis, controversy continues in the management
      of asymptomatic and recurrent carotid stenosis. Medical management options and
      effectiveness has significantly improved since the early CEA trials were
      published. Optimal medical management now must incorporate aggressive risk factor
      reduction measures, particularly with antihyperlipidemic therapy. Improved
      understanding of the natural history of carotid atherosclerosis is necessary to
      improve the application of management strategies.

PMID- 20798074
TI  - Commentary on "Medical management of carotid stenosis".

PMID- 20798075
TI  - Carotid artery disease: selecting the appropriate asymptomatic patient for
      intervention.
AB  - Despite randomized controlled trials demonstrating the superiority of carotid
      endarterectomy over medical management in the prevention of stroke in
      asymptomatic patients with severe carotid artery stenosis, considerable
      controversy remains with regard to selecting the appropriate asymptomatic patient
      for carotid intervention. Adding to the complexity of this issue is the fact that
      the extensive existing literature on this topic is heterogeneous, with trials
      having used varying definitions of high-grade stenosis, inclusion criteria for
      patients, and outcome measurements. The current article will review the existing
      randomized controlled trials on this topic, data regarding the risk of stroke in
      asymptomatic patients with severe stenosis, data regarding subsets of
      asymptomatic patients that may be at a higher-than-average risk of future stroke,
      and data regarding the efficacy of current medical therapy on the risk of stroke
      in asymptomatic patients with high-grade stenosis. Ultimately, the challenge for
      clinicians is to ensure that asymptomatic patients with the highest risk of
      future stroke are offered carotid revascularization and that the intervention is
      performed with the lowest possible complication rate, in order to maintain the
      benefit of prophylactic treatment.

PMID- 20798076
TI  - Commentary on "Carotid artery disease: selecting the appropriate asymptomatic
      patient for intervention".

PMID- 20798077
TI  - Who is unfit for carotid endarterectomy?
AB  - Carotid endarterectomy (CEA) has long been considered the "gold standard" in the
      treatment of patients with symptomatic or asymptomatic carotid stenosis. However,
      the utility of this treatment modality in medical or surgical "high-risk"
      patients remains in question. Numerous clinical trials have demonstrated that
      carotid angioplasty and stenting (CAS) is not inferior to CEA. Furthermore, there
      are also increasing data that show that best medical therapy is becoming more
      effective in preventing strokes and in a more cost-effective manner than carotid
      interventions. With this in mind, there is now ample evidence to suggest that in
      a certain subgroup of patients, CEA may not be indicated, and in fact, CAS or
      observation with best medical therapy is preferred.

PMID- 20798078
TI  - Commentary on "Who is unfit for carotid endarterectomy?".

PMID- 20798079
TI  - Carotid intervention in acute stroke.
AB  - With advances in acute stroke management, patients with symptomatic severe
      carotid stenosis are frequently evaluated in the acute stage (ie, within the
      first few hours) after onset of symptoms. Patients with severe extracranial
      carotid artery stenosis presenting with acute stroke often have associated
      intracranial occlusive lesions. When invasive intra-arterial therapy is
      indicated, both revascularization of the extracranial and of the intracranial
      occlusive lesion is warranted to achieve a good functional outcome. In patients
      presenting with acute stroke, revascularization of severe extracranial carotid
      stenosis and even frank occlusion is possible; it improves distal flow and allows
      easier access to the often coexistent intracranial occlusion. In this article,
      the authors review the indications, techniques, and results of acute carotid
      interventions for acute stroke.

PMID- 20798080
TI  - Commentary on "Carotid interventions in acute stroke".

PMID- 20798081
TI  - PDBj Mine: design and implementation of relational database interface for Protein
      Data Bank Japan.
AB  - This article is a tutorial for PDBj Mine, a new database and its interface for
      Protein Data Bank Japan (PDBj). In PDBj Mine, data are loaded from files in the
      PDBMLplus format (an extension of PDBML, PDB's canonical XML format, enriched
      with annotations), which are then served for the user of PDBj via the worldwide
      web (WWW). We describe the basic design of the relational database (RDB) and web
      interfaces of PDBj Mine. The contents of PDBMLplus files are first broken into
      XPath entities, and these paths and data are indexed in the way that reflects the
      hierarchical structure of the XML files. The data for each XPath type are saved
      into the corresponding relational table that is named as the XPath itself. The
      generation of table definitions from the PDBMLplus XML schema is fully automated.
      For efficient search, frequently queried terms are compiled into a brief summary
      table. Casual users can perform simple keyword search, and 'Advanced Search'
      which can specify various conditions on the entries. More experienced users can
      query the database using SQL statements which can be constructed in a uniform
      manner. Thus, PDBj Mine achieves a combination of the flexibility of XML
      documents and the robustness of the RDB. Database URL: http://www.pdbj.org/

PMID- 20798082
TI  - Measuring processes of care in general surgery: assessment of technical and
      nontechnical skills.
AB  - Measuring the quality of health care is becoming increasingly important. Quality
      is often conceptualized as 3 dimensions of care: structures, processes, and
      outcomes. Unfortunately, there is little consensus about what should be measured-
      and how it should be measured--when it comes to measuring processes of care
      related to the conduct of surgical procedures. This article reviews recent
      advances in surgical quality of care measurement with particular emphasis on
      processes of care, and evaluates existing measures of technical and nontechnical
      surgical skills as measures of quality of care in surgery.

PMID- 20798083
TI  - Learner's evaluation in paediatric intensive care unit.
AB  - OBJECTIVE: To compare post-paediatric intensive care unit (PICU) rotation
      performance of paediatric residents (PGY-2) and emergency residents (PGY-2) on an
      online test developed by the subcommittee of the paediatric section of the
      Society of Critical Care Medicine. Also, to compare residents' performance with
      that of physician extenders. DESIGN AND SETTINGS: A single centre, longitudinal,
      retrospective, quality improvement data review in a tertiary care, 20-bed PICU.
      The test was securely submitted to all residents at the end of their PICU
      rotation from July 2005 to June 2008. The test was also submitted to physician
      extenders once only during the 3-year study period. RESULTS: The mean, paediatric
      residents' (N=30) score was 77.3%+/-10.8 (SD) and that of emergency residents
      (N=40) was 82.3%+/-8.2 (SD) at PGY-2 level (p=0.03). The combined paediatric
      residents' and emergency residents' mean score was 80.1%+/-9.7 (SD). The mean
      physician extenders' (N=7) score was 80.1%+/-6.5 (SD). CONCLUSION: Emergency
      residents performed slightly better than paediatric residents on the paediatric
      focused knowledge-based online test. The physician extenders' performance was
      comparable to the individual resident groups' performance and their combined
      performance.

PMID- 20798084
TI  - Clinical characteristics of mephedrone toxicity reported to the U.K. National
      Poisons Information Service.
AB  - OBJECTIVE: To describe the patterns and clinical features of toxicity related to
      recreational use of mephedrone and other cathinones in the U.K. using data
      collected by the National Poisons Information Service (NPIS). METHODS: The number
      of accesses to TOXBASE, the NPIS online poisons information database, details of
      consecutive cases uploaded onto TOXBASE and the number and details of telephone
      enquiries made to the NPIS by health professionals in the U.K. were collected for
      the period March 2009 to February 2010. RESULTS: Over the year of study there
      were 2901 TOXBASE accesses and 188 telephone enquiries relating to cathinones,
      the majority relating to mephedrone (TOXBASE 1664, telephone 157), with a month
      on-month increase in numbers. In 131 telephone enquiries concerning mephedrone,
      alone or in combination with alcohol, common clinical features reported included
      agitation or aggression (n=32, 24%, 95% CI 18% to 33%), tachycardia (n=29, 22%,
      95% CI 16% to 30%), confusion or psychosis (n=18, 14%, 95% CI 9% to 21%), chest
      pain (n=17, 13%, 95% CI 8% to 20%), nausea (n=15, 11%, 95% CI 7% to 18%),
      palpitations (n=14, 11%, 95% CI 6% to 18%), peripheral vasoconstriction (n=10,
      8%, 95% CI 4% to 14%) and headache (n=7, 5%, 95% CI 2% to 11%). Convulsions were
      reported in four cases (3%, 95% CI 1% to 8%). One exposed person died following
      cardiac arrest (1%, 95% CI 0% to 4%), although subsequent investigation suggested
      that mephedrone was not responsible. CONCLUSIONS: Toxicity associated with
      recreational mephedrone use is increasingly common in the UK. Sympathomimetic
      adverse effects are common and severe effects are also reported. Structured data
      collected by the NPIS may be of use in identifying trends in poisoning and in
      establishing toxidromes for new drugs of abuse.

PMID- 20798085
TI  - Acute dyspnoea in a 52-year-old man.

PMID- 20798086
TI  - Images in emergency medicine. Detection of hepatic portal venous gas on emergent
      CT.

PMID- 20798087
TI  - Abdominal compartment syndrome induced by massive pneumoperitoneum.

PMID- 20798088
TI  - A case of transdiaphragmatic intercostal hernia: the efficacy of using
      multidetector-row CT with multiplanar reformation.

PMID- 20798089
TI  - Trauma care in England: London's trauma system goes live.

PMID- 20798091
TI  - Back and leg pain due to a spinal synovial cyst.

PMID- 20798090
TI  - Role of ambulance response times in the survival of patients with out-of-hospital
      cardiac arrest.
AB  - OBJECTIVES: To evaluate the role of ambulance response times in improving
      survival for out-of-hospital cardiac arrest (OHCA). METHODS: OHCAs were
      identified by sampling consecutive life-threatening category A emergency
      ambulance calls on an annual basis for the 5 years 1996/7-2000/1 from four
      ambulance services in England. From these, all calls where an ambulance arrived
      at the scene and treated or transported a patient were included in the study.
      These cohorts of patients were followed up to discharge from hospital. RESULTS:
      Overall, 30 (2.6%) of the 1161 patients with cardiac arrest survived to hospital
      discharge. If the patient arrested while the paramedics were on scene, survival
      to hospital discharge was 14%. The most important predictive factors for survival
      were response time, initial presenting heart rhythm in ventricular fibrillation
      and whether the arrest was witnessed. The estimated effect of a 1&emsp14;min
      reduction in response time was to improve the odds of survival by 24% (95% CI 4%
      to 48%). The costs of reducing response times across the board by 1 at the time
      of this study were estimated at around L54 million. CONCLUSIONS: The arrival of a
      crew prior to OHCA means that the chance of surviving the arrest increases
      sevenfold. Overall it is possible that rapid response to patients in immediate
      risk of arrest may be at least as beneficial as rapid response to those who have
      arrested. Concentrating resources on reducing response times across the board to
      improve survival for those patients already in arrest is unlikely to be a cost
      effective option to the U.K. National Health Service.

PMID- 20798092
TI  - If they build it, why don't we come?

PMID- 20798093
TI  - Adhesion prevention and reduction: current status and future recommendations of a
      multinational interdisciplinary consensus conference.
AB  - Adhesions can be found after virtually every abdominopelvic operation performed
      through standard laparotomy as well as by laparoscopic approaches. Adhesions can
      be completely asymptomatic or can cause significant morbidity and mortality
      including strangulation, obstruction, and necrosis of bowel loops and/or
      infertility and organ injury during repeat abdominal surgery. Perhaps because of
      the multifactorial nature of adhesion development, prevention has been very
      limited. Three anti-adhesion products are commercially available, none of which
      has been universally accepted as a panacea. Part of the obstacles with adhesion
      management is the lack of an objective clinically relevant classification to
      allow their study. Because a single band can cause a life-threatening bowel
      obstruction, whereas extensive dense intra-abdominal adhesions may be
      asymptomatic, neither the mere presence or absence of adhesions nor their extent
      if present is totally adequate endpoints. Adhesions are a major health care
      burden, and their reduction is a significant unmet need in surgical therapeutics
      facing all surgeons. Of all the parameters assessing adhesions currently
      available, the authors believe that adhesion incidence (presence or absence) is
      the most relevant endpoint with a direct clinical implication. The authors
      endorse the development of a validated, clinically relevant scale to assess intra
      abdominal adhesions. Given the present limitation of objective assessment of
      adhesions and prediction of their clinical effect, the authors also advocate,
      when appropriate, the use of one of the Food and Drug Administration-approved
      adhesion barriers. Further research is required to develop safe and effective
      anti-adhesion methods as well as better assessment tools for their efficacy.

PMID- 20798094
TI  - Impact of heavy polypropylene mesh and composite light polypropylene and
      polyglactin 910 on the inflammatory response.
AB  - The aim of the study was to analyze the acute inflammatory response after
      implantation of a heavyweight mesh of polypropylene (PP) compared with a
      composite mesh of light PP and polyglactin 910 (PG) in patients undergoing
      inguinal hernioplasty. A total of 30 male patients with inguinal hernia were
      included in the study and divided into 2 groups (PP and PP-PG) according to the
      mesh used. Changes of leukocytes, cytokines, growth factors, and acute phase
      proteins were evaluated in the sera. Leukocytes and acute phase proteins were
      significantly increased postoperatively in both groups, and the values were
      slightly higher in the PP group. Cytokine levels were significantly increased
      postoperatively in both groups; a slight increase was observed in the PP-PG
      group, especially for the proinflammatory cytokine. Growth factors decreased
      significantly in both groups immediately after surgery. The authors found that
      the use of the mesh is a stimulator of inflammatory response, and the 2 types of
      mesh induce a similar inflammatory response.

PMID- 20798095
TI  - Single-port laparoscopic umbilical hernia repair.
AB  - BACKGROUND: Laparoscopic umbilical herniorrhaphy is preferred when abdominal wall
      defects exceed 3 cm. The authors describe a novel single-port laparoscopic
      technique for umbilical hernia repair. METHODS: A total of 10 patients underwent
      single-port laparoscopic umbilical hernia repair. A 10-mm endoscope with a
      working channel was placed in the left upper quadrant. The abdominal wall defect
      was covered with a circular mesh with pretied sutures and needles attached. The
      mesh was secured to the abdominal wall with intraabdominal sutures without the
      need for transfascial suture fixation. RESULTS: The average age of the patients
      was 43 years, and the average BMI was 34 kg/m(2). All procedures were completed
      laparoscopically. The mean operative time was 73 minutes. No major intraoperative
      or postoperative complications were encountered. CONCLUSIONS: Single-port
      laparoscopic umbilical hernia repair is a safe and easily reproducible novel
      technique. It can help reduce possible complications from multiple-port sites.

PMID- 20798096
TI  - A time to every purpose.

PMID- 20798097
TI  - The additional use of end-tidal alveolar dead space fraction following D-dimer
      test to improve diagnostic accuracy for pulmonary embolism in the emergency
      department.
AB  - PURPOSE: To determine the diagnostic performance of bedside assessment of end
      tidal alveolar dead space fraction (ADSF) for pulmonary embolism (PE) and whether
      the use of additional ADSF assessment following D-dimer assay can improve the
      diagnostic accuracy in suspected PE patients in the emergency department.
      METHODS: A prospective observational study of 112 consecutive adult patients
      suspected of PE of whom 102 were eligible for analysis. ADSF was calculated using
      arterial carbon dioxide and end-tidal carbon dioxide. An ADSF less than 0.2 was
      considered normal. RESULTS: PE was confirmed in 11 (10.8%) of 102 patients. D
      dimer assay alone as a reference standard test for PE had a sensitivity of 100%,
      specificity of 38.5% and false negativity of 0%. Area under the receiver-operator
      characteristic curve for the diagnosis of PE using ADSF values alone was 0.894,
      Sensitivity, specificity and false negativity for the combined results of a
      positive D-dimer test and abnormal ADSF were 100%, 78.0% and 0% for the presence
      of PE, respectively. Of 65 patients with a low or intermediate clinical
      probability and a positive D-dimer assay, 36 (55.4%) patients displayed normal
      ADSF and had no PE. CONCLUSIONS: By itself ADSF assessment performed well in
      diagnosis of PE. The combined result of a positive D-dimer and abnormal ADSF
      increased the specificity for diagnosing PE compared with the D-dimer test alone.
      The use of additional bedside ADSF assessment following a positive D-dimer test
      may reduce the need for further imaging studies to detect PE in patients with a
      low or intermediate clinical probability.

PMID- 20798098
TI  - Giant right vertebral artery aneurysm.

PMID- 20798099
TI  - Purple urine bag syndrome.

PMID- 20798100
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 1: intranasal fentanyl or diamorphine versus intravenous morphine
      for analgesia in adults.

PMID- 20798102
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 2: dexamethasone versus prednisolone in asthma.

PMID- 20798103
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 3: non-invasive ventilation in hypercapnic coma.

PMID- 20798104
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 4: whole-body CT in trauma patients.

PMID- 20798105
TI  - Cardiac arrest in infancy: don't forget glucose!
AB  - A 2-year-old girl was brought to the Emergency Department having collapsed at
      home. She was unconscious and apnoeic with a sinus bradycardia of 50 beats/min.
      Cardiopulonary resuscitation (CPR) was commenced and her airway was secured.
      Epinephrine and atropine were administered. The blood glucose was found to be
      <0.5 mmol/l. There were minimal ketones found in both urine and serum. A bolus of
      5 ml/kg of 10% dextrose was administered. Following a third cycle of CPR, a
      strong pulse was palpated with a sinus tachycardia. Subsequent metabolic
      screening tests confirmed a diagnosis of medium chain acyl-CoA dehydrogenase
      (MCAD) deficiency. Despite the higher prevalence of hypoglycaemia in children
      requiring non-trauma-related resuscitation care, there is significant variability
      in time to checking blood glucose. In any clinical situation necessitating fatty
      acid oxidation, such as periods of fasting or metabolic stress due to
      intercurrent illness or infection, patients with MCAD deficiency will have
      continued glucose consumption with reduced or absent formation of ketones. The
      result of this is severe hypoglycaemia and hypoketonuria. 18% of patients with
      MCAD deficiency present with sudden death, and total mortality rate before
      diagnosis is estimated at 24%. Without diagnosis, preventative interventions to
      avoid further metabolic decompensation and possible neurological involvement
      could not be made.

PMID- 20798106
TI  - Haemorrhage requiring embolisation after low energy pelvic fracture in an elderly
      patient: a case report.
AB  - An 89-year-old woman presented with a stable fracture of the pelvis following a
      low energy trauma. The patient was taking no anticoagulation medication and was
      found to have life-threatening pelvic bleeding which required embolisation.
      Stable pelvic fractures following low energy trauma are common injuries in the
      elderly and frequently require admission for pain relief and mobility management.
      This case highlights that severe pelvic bleeding is a possible, life-threatening
      sequela after low energy pelvic injury in the elderly, and careful attention must
      be paid to the signs of active haemorrhage.

PMID- 20798107
TI  - Management of ingested dentures.

PMID- 20798109
TI  - Transcribed dark matter: meaning or myth?
AB  - Genomic tiling arrays, cDNA sequencing and, more recently, RNA-Seq have provided
      initial insights into the extent and depth of transcribed sequence across human
      and other genomes. These methods have led to greatly improved annotations of
      protein-coding genes, but have also identified transcription outside of annotated
      exons. One resultant issue that has aroused dispute is the balance of
      transcription of known exons against transcription outside of known exons. While
      non-genic 'dark matter' transcription was found by tiling arrays to be pervasive,
      it was seen to contribute only a small percentage of the polyadenylated
      transcriptome in some RNA-Seq experiments. This apparent contradiction has been
      compounded by a lack of clarity about what exactly constitutes a protein-coding
      gene. It remains unclear, for example, whether or not all transcripts that
      overlap on either strand within a genomic locus should be assigned to a single
      gene locus, including those that fail to share promoters, exons and splice
      junctions. The inability of tiling arrays and RNA-Seq to count transcripts,
      rather than exons or exon pairs, adds to these difficulties. While there is
      agreement that thousands of apparently non-coding loci are present outside of
      protein-coding genes in the human genome, there is vigorous debate of what
      constitutes evidence for their functionality. These issues will only be resolved
      upon the demonstration, or otherwise, that organismal or cellular phenotypes
      frequently result when non-coding RNA loci are disrupted.

PMID- 20798110
TI  - The role of threats in animal cooperation.
AB  - In human societies, social behaviour is strongly influenced by threats of
      punishment, even though the threats themselves rarely need to be exercised.
      Recent experimental evidence suggests that similar hidden threats can promote
      cooperation and limit within-group selfishness in some animal systems. In other
      animals, however, threats appear to be ineffective. Here I review theoretical and
      empirical studies that help to understand the evolutionary causes of these
      contrasting patterns, and identify three factors-impact, accuracy and perception
      that together determine the effectiveness of threats to induce cooperation.

PMID- 20798111
TI  - Universal scaling of production rates across mammalian lineages.
AB  - Over many millions of years of independent evolution, placental, marsupial and
      monotreme mammals have diverged conspicuously in physiology, life history and
      reproductive ecology. The differences in life histories are particularly
      striking. Compared with placentals, marsupials exhibit shorter pregnancy, smaller
      size of offspring at birth and longer period of lactation in the pouch.
      Monotremes also exhibit short pregnancy, but incubate embryos in eggs, followed
      by a long period of post-hatching lactation. Using a large sample of mammalian
      species, we show that, remarkably, despite their very different life histories,
      the scaling of production rates is statistically indistinguishable across
      mammalian lineages. Apparently all mammals are subject to the same fundamental
      metabolic constraints on productivity, because they share similar body designs,
      vascular systems and costs of producing new tissue.

PMID- 20798112
TI  - Influence of oceanic factors on Anguilla anguilla (L.) over the twentieth century
      in coastal habitats of the Skagerrak, southern Norway.
AB  - The European eel (Anguilla anguilla L.) is distributed in coastal and inland
      habitats all over Europe, but spawns in the Sargasso Sea and is thus affected by
      both continental and oceanic factors. Since the 1980s a steady decline has been
      observed in the recruitment of glass eels to freshwater and in total eel
      landings. The eel is considered as critically endangered on the International
      Union for the Conservation of Nature and Natural Resources Red List of species.
      The Skagerrak beach seine survey from Norway constitutes the longest fishery
      independent dataset on yellow/silver eels (starting in 1904). The Skagerrak
      coastal region receives larvae born in the Sargasso Sea spawning areas that have
      followed the Gulf Stream/North Atlantic Drift before they penetrate far into the
      North Sea. The Skagerrak coastal time series is therefore particularly valuable
      for exploring the impacts of oceanic factors on fluctuations in eel recruitment
      abundance. Analyses showed that Sargasso Sea surface temperature was negatively
      correlated with eel abundance, with a lag of 12 years revealing a cyclic and
      detrimental effect of high temperatures on the newly hatched larvae. The North
      Atlantic Oscillation index and inflow of North Atlantic water into the North Sea
      were negatively correlated with eel abundance, with a lag of 11 years. Increased
      currents towards the North Atlantic during high North Atlantic Oscillation years
      may send larvae into the subpolar gyre before they are ready to metamorphose and
      settle, resulting in low recruitment in the northern part of the distribution
      area for these years. The Skagerrak time series was compared with glass eel
      recruitment to freshwater in the Netherlands (Den Oever glass eel time series),
      and similar patterns were found revealing a cycle linked to changes in oceanic
      factors affecting glass eel recruitment. The recent decline of eels in the
      Skagerrak also coincided with previously documented shifts in environmental
      conditions of the North Sea ecosystem.

PMID- 20798113
TI  - Evolution of nutrient acquisition: when adaptation fills the gap between
      contrasting ecological theories.
AB  - Although plant strategies for acquiring nutrients have been widely studied from a
      functional point of view, their evolution is still not well understood. In this
      study, we investigate the evolutionary dynamics of these strategies and determine
      how they influence ecosystem properties. To do so, we use a simple nutrient
      limited ecosystem model in which plant ability to take up nutrients is subject to
      adaptive dynamics. We postulate the existence of a trade-off between this ability
      and mortality. We show that contrasting strategies are possible as evolutionary
      outcomes, depending on the shape of the trade-off and, when nitrogen is
      considered as the limiting nutrient, on the intensity of symbiotic fixation. Our
      model enables us to bridge these evolutionary outcomes to classical ecological
      theories such as Hardin's tragedy of the commons and Tilman's rule of R*.
      Evolution does not systematically maximize plant biomass or primary productivity.
      On the other hand, each evolutionary outcome leads to a decrease in the
      availability of the limiting mineral nutrient, supporting the work of Tilman on
      competition between plants for a single resource. Our model shows that evolution
      can be used to link different classical ecological results and that adaptation
      may influence ecosystem properties in contrasted ways.

PMID- 20798114
TI  - Production and characterization of a monomeric form and a single-site form of
      Aleuria aurantia lectin.
AB  - Lectins have widely been used in structural and functional studies of complex
      carbohydrates. They usually bind carbohydrates with relatively low affinity, but
      compensate for this by multivalency. This multivalent nature of lectins can
      sometimes produce unwanted reactions such as agglutination or precipitation of
      target glycoproteins, when using them in different biological and analytical
      assays. The mushroom lectin Aleuria aurantia binds to fucose-containing
      oligosaccharides. It is composed of two identical subunits, and each subunit
      contains five binding sites for fucose. In this study, two forms of recombinant
      AAL were produced using site-directed mutagenesis. A monomeric form of AAL was
      produced by exchanging Tyr6 with Arg6, and a single-site fragment of AAL was
      produced by insertion of an NdeI restriction enzyme cleavage site and a stop
      codon in the coding sequence. The AAL forms were expressed as His-tagged proteins
      in Escherichia coli and purified by affinity chromatography. Binding properties
      of the two AAL forms were performed using surface plasmon resonance, enzyme
      linked lectin assay analyses and isothermal titration calorimetry. Both the
      monomeric AAL (mAAL) and the single-site AAL (S2-AAL) forms retained their
      capacity to bind fucosylated oligosaccharides. However, both constructs exhibited
      properties that differed from the intact recombinant AAL (rAAL). mAAL showed
      similar binding affinities to fucosylated oligosaccharides as rAAL, but had less
      hemagglutinating capacity. S2-AAL showed a lower binding affinity to fucosylated
      oligosaccharides and, in contrast to rAAL and mAAL, S2-AAL did not bind to
      sialylated fuco-oligosaccharides. The study shows that molecular engineering is a
      highly useful tool for producing lectins with more defined properties such as
      decreased valency and defined specificities and affinities. Thus, this approach
      has high potential in developing reliable diagnostic and biological assays for
      carbohydrate analysis.

PMID- 20798115
TI  - Supraclavicular vein approach to overcoming ipsilateral chronic subclavian vein
      obstruction during pacemaker-ICD lead revision or upgrading.
AB  - AIMS: We report our experience with the supraclavicular vein approach of
      subclavian vein puncture to overcome ipsilateral chronic obstruction when
      implanting pacemaker or implantable cardioverter defibrillator leads. METHODS AND
      RESULTS: The subclavian vein obstruction was documented by venography. The skin
      was punctured with an 18-gauge needle, 1 cm lateral to the lateral head of the
      sternocleidomastoid muscle and 1 cm cranial to the clavicle. The needle was
      directed under and close to the clavicle pointing to the sternal notch. Once the
      vein was successfully punctured, medial to the obstruction, a 0.38 in. guidewire
      was inserted into the venous bed. A peel-away sheath was indwelled using the
      Seldinger technique. The leads were placed in the standard fashion; they were
      secured by suture to the subcutaneous tissue of the fossa supraclavicularis major
      using a protective sleeve. The proximal portion of the lead was tunnelled over
      the clavicle down to the device's prepectoral pocket. Lead insertion was
      performed in four patients (twice in one patient) with total left subclavian vein
      obstruction; the site of the obstruction was in the mid-segment of the left
      subclavian vein in two patients, in the axillary and distal segment of the
      subclavian vein in one patient, and in the distal segment of the subclavian vein
      in one patient. There were no complications with the surgical wound and the lead
      parameters remained stable. CONCLUSION: The supraclavicular approach of the
      subclavian vein puncture to overcome ipsilateral total occlusion is feasible and
      safe.

PMID- 20798116
TI  - Electrocardiogram-electrogram desynchronization while using radiofrequency
      wandless telemetry during implantation of an implantable cardioverter
      defibrillator.

PMID- 20798117
TI  - Efficacy of flecainide in a patient with catecholaminergic polymorphic
      ventricular tachycardia.

PMID- 20798118
TI  - Characteristics of patients and implantable defibrillators associated with
      failure to sense device alert systems.
AB  - AIMS: In the era of increasing implantable cardioverter defibrillator (ICD)
      complexity, the ICD patient alert is deemed to be an important feature in the
      early detection of ICD system malfunction and is either an audible or a vibratory
      alert. We sought to evaluate the patient's ability to detect these ICD alerts in
      the device clinic setting as a surrogate endpoint of clinical utility. METHODS
      AND RESULTS: From 1 November 2006 to 31 March 2008, 563 patients with an ICD
      equipped with either an audible patient alert (APA, Medtronic and Guidant; n =
      485) or a vibratory monitoring alert ([VMA, St Jude Medical; n = 78) had their
      alarm demonstrated in the quiet clinic setting. The ability to recognize the
      alert was analysed and then stratified by gender, age, manufacturer, type of
      alert, and pocket location. The average patient age was 63.3 (+/- 13.6) years and
      82.8% of patients were male. Implantable cardioverter defibrillator manufacturers
      were Medtronic (n = 464), Boston Scientific (n = 21), and SJM (n = 78). The APA
      was heard in 86.0% of patients. This was less likely in patients who were older,
      male, and where the device was placed in the submuscular position. Every patient
      with a VMA sensed their alert. CONCLUSION: In the current ICD alert technology,
      the ability to sense the ICD alert in the device clinic appears to be higher for
      the VMA than for the APA. In particular, older patients and male patients are
      less likely to sense the APA.

PMID- 20798119
TI  - An unexpected vein draining into the left atrial roof.

PMID- 20798120
TI  - Para- and perirenal fat thickness is an independent predictor of chronic kidney
      disease, increased renal resistance index and hyperuricaemia in type-2 diabetic
      patients.
AB  - BACKGROUND: Many interfering factors may reduce the reliability of waist
      circumference (WC) measurement in estimating the risk for chronic kidney disease
      (CKD) associated with obesity. Therefore, we determined the independent
      associations of para- and perirenal ultrasonographic fat thickness with the main
      markers of kidney function. METHODS: A cross-sectional study was performed in 151
      type-2 diabetic subjects. Para- and perirenal fat thickness was measured from the
      inner side of the abdominal musculature to the surface of the kidneys. CKD was
      defined as eGFR < 60 mL min(-1)1.73 m(-2). RESULTS: Using both univariate and
      multivariate regression analyses, eGFR, renal resistance index and uricaemia were
      best predicted by para- and perirenal fat thickness even when BMI and waist
      circumference were further added in the statistical model (r(2): 0.366, P =
      0.001; r(2): 0.529, P = 0.005; r(2): 0.310, P = 0.026, respectively), whereas
      waist circumference and BMI did not contribute independently of para- and
      perirenal fat thickness. Albuminuria was predicted by waist circumference but not
      by para- and perirenal fat thickness. In subjects with waist circumference above
      the diagnostic values of metabolic syndrome (48M/59F), eGFR significantly and
      progressively declined across tertiles of para- and perirenal fat thickness (87.0
      +/- 27.9 vs 83.5 +/- 26.0 vs 62.3 +/- 30.6 mL min(-1) 1.73 m(-2), adjusted P <
      0.0001) despite comparable waist circumference, and an increasing frequency of
      CKD was observed across tertiles of subjects with waist circumference both below
      and above the metabolic syndrome diagnostic values (P < 0.05). CONCLUSIONS: Para-
      and perirenal fat thickness is an independent predictor of kidney dysfunction in
      type-2 diabetes explaining an important proportion of the variance of eGFR, renal
      resistance index and uricaemia.

PMID- 20798121
TI  - Autosomal dominant polycystic kidney disease and mTOR inhibitors: the narrow road
      between hope and disappointment.

PMID- 20798122
TI  - Welcome to MEPE in the renal proximal tubule.

PMID- 20798123
TI  - A homozygous mutation in INVS causing juvenile nephronophthisis with abnormal
      reactivity of the Wnt/beta-catenin pathway.
AB  - Mutations in the INVS gene coding for inversin have been identified in patients
      with nephronophthisis type 2 (NPHP2), typically causing infantile onset of ESRD
      and potentially associated with situs inversus. We report a novel family with a
      homozygous INVS mutation (c.2695 C > T; p.Arg899X) deleting the C-terminus of
      inversin. Both affected patients had juvenile ESRD and were discordant for situs
      inversus. The end-stage kidneys showed chronic interstitial nephritis with cysts
      and abnormal expression of beta-catenin and Dishevelled-1 supporting up-regulated
      canonical Wnt pathway in tubular cells. This case shows that INVS mutation can
      cause juvenile nephronophthisis with abnormal reactivity of the Wnt/beta-catenin
      pathway.

PMID- 20798124
TI  - Bayesian hierarchical modeling of latent period switching in small-area putative
      health hazard studies.
AB  - In recent years, small area risk assessment modelling and data analysis around
      putative hazard sources has become a fundamental part of public health and
      environmental sciences. In this study, we address a fundamental problem in the
      analysis of such data, when intermittent operation of facilities could lead to
      evidence for latent periods of risk. This study examines the development of
      Bayesian models for the latent switching operating period of putative hazard
      sources such as nuclear processing plants and waste disposal incinerators. The
      developed methodology is applied in a simulation study as well as to a real data
      example.

PMID- 20798125
TI  - The World Health Report 2000: expanding the horizon of health system performance.

PMID- 20798126
TI  - The World Health Report 2000: 10 years on.

PMID- 20798127
TI  - WHR 2000 to WHR 2010: what progress in health care financing?

PMID- 20798128
TI  - STXBP2 mutations in children with familial haemophagocytic lymphohistiocytosis
      type 5.
AB  - BACKGROUND: Familial haemophagocytic lymphohistiocytosis (FHL) is a rare immune
      deficiency with uncontrolled inflammation; the clinical course usually starts
      within the first years of life, and is usually fatal unless promptly treated and
      then cured with haematopoietic stem cell transplant. FHL is caused by genetic
      mutations resulting in defective cell cytotoxicity; three disease related genes
      have been identified to date: perforin, Munc13-4 and syntaxin-11. A fourth gene,
      STXBP2, has been identified very recently as responsible for a defect in Munc18-2
      in FHL-5. AIMS: To describe the result of the screening of families with HLH and
      previously unassigned genetic defects. METHODS: Patients with HLH diagnosed
      according to current diagnostic criteria, and who lacked mutations in the PRF1,
      Munc13-4, and STX11 genes were sequenced for mutations in STXBP2. Functional
      study was performed when material was available. RESULTS: Among the 28 families
      investigated, 4 (14%) with biallelic STXBP2 mutations were identified. They
      originated from Italy, England, Kuwait and Pakistan. The p.Pro477Leu resulting
      from c.1430C>T, and p.Arg405Gln resulting from the single c.1214G>A nucleotide
      change are known, while we contribute two novel mutations: p.Glu132Ala resulting
      from c.395A>C, and p.Gly541Ser, resulting from c.1621G>A. The detrimental effect
      of the p.Gly541Ser mutation was documented biochemically and functionally in NK
      and CD8 cells. Additional polymorphisms are also described. CONCLUSION: These
      data expand current knowledge on the genetic heterogeneity of FHL and suggest
      that patients with FHL5 may have different results in degranulation assays under
      different conditions.

PMID- 20798129
TI  - Oesophageal squamous cell carcinoma in a young adult with IL-12R beta 1
      deficiency.
AB  - Genetic defects in the IL-12-IL-23/IFN-gamma circuit confer Mendelian
      susceptibility to mycobacteria and salmonella. The IL-12/IFN-gamma axis is
      essential for anti-tumoral immunity in mice. Cancer susceptibility has not been
      recognised in these patients so far. We report three relatives with IL-12R beta 1
      deficiency. At the age of 25 years old, one patient presented with oesophageal
      squamous cell carcinoma (OSCC). The patient had no previous risk factors for
      OSCC. He died at the age of 29 years. OSCC is exceedingly rare in individuals
      under 30 years and frequently relates to alcohol intake and smoking. Disorders of
      the IL-12-IL-23/IFN-gamma axis may predispose to cancer.

PMID- 20798130
TI  - Aliskiren, a renin inhibitor, downregulates TNF-alpha-induced tissue factor
      expression in HUVECS.
AB  - Angiotensin (Ang)II, the effector arm of the locally active renin-angiotensin
      system (RAS), modulates Tissue Factor (TF), the principal initiator of blood
      coagulation and a key promoter of atherothrombotic events. Consistent with that
      knowledge, previous data showed inhibitory properties of angiotensin-converting
      enzyme inhibitor (ACEI)s and angiotensin II type-1 receptor blocker (ARB)s, but
      no data are available about the effect of renin inhibition. We aimed to evaluate
      whether aliskiren, a direct renin inhibitor (DRI), modulates TNF-alpha-stimulated
      TF expression in cultured human umbilical vein endothelial cells (HUVECs).
      Zofenopril, an ACEI, and olmesartan, an ARB, were the controls. HUVECs were
      incubated with experimental drugs (1 nM) 30 min prior to TNF-alpha stimulation
      (0.1 ng/ml * 4 h). Main evaluation variables were procoagulant activity (single
      stage clotting assay), TF antigen (ELISA) and mRNA expression (real-time
      polymerase chain reaction) in cell lysates. TNF-alpha stimulated procoagulant
      activity and increased TF antigen and mRNA expression. Aliskiren inhibited TNF
      alpha-mediated TF stimulation; zofenopril and olmesartan exerted a comparable
      effect. We conclude that aliskiren, a DRI, downregulates TNF-alpha-stimulated TF
      expression in HUVECs, possibly as a reflection of endothelial renin activation by
      the cytokine.

PMID- 20798131
TI  - Sex hormone regulation of survivin gene expression.
AB  - Survivin (BIRC5) is a cell survival gene that is overexpressed in endometrial
      cancer and has been implicated to have a physiological role in normal endometrial
      function. To determine whether survivin gene expression is regulated by
      reproductive steroid hormones in the human endometrium, RNA was prepared from
      normal cycling women in the proliferative and secretory phases of the menstrual
      cycle. RNA was also isolated from 21 endometrial biopsies from premenopausal
      women at baseline and following 3 months of treatment with depot
      medroxyprogesterone acetate. Finally, RNA was isolated from endometrial biopsies
      from ten healthy postmenopausal women participating in a clinical trial of
      estrogen replacement therapy at baseline and following 6 months of treatment with
      conjugated equine estrogen. Quantitative RT-PCR analysis was used to determine
      survivin, insulin-like growth factor binding protein 1 (IGFBP1), Ki67, and IGF1
      gene expression levels. Survivin gene expression was highest in the proliferative
      phase of the menstrual cycle and showed a statistically significant 4-fold
      increase in expression following chronic treatment with estrogens; this was
      strongly correlated with increased Ki67, a marker of proliferation. Survivin gene
      expression decreased 4.6-fold following chronic progestin treatment in the human
      endometrium. These data suggest that survivin transcript is regulated by
      estrogens and progestins in the disease-free human endometrium. The data also
      suggest that survivin transcript may be used as a biomarker of estrogen and
      progestin treatment efficacy, but validation studies must be conducted to support
      this conclusion.

PMID- 20798132
TI  - An IGF1/insulin receptor substrate-1 pathway stimulates a mitotic kinase (cdk1)
      in the uterine epithelium during the proliferative response to estradiol.
AB  - Estrogens are potent mitogens for some target organs, such as the uterus, and
      cancers that develop in this organ might be linked to the proliferative action of
      these hormones. However, the mechanism by which estrogens influence the cell
      cycle machinery is not known. We found that a null mutation for the insulin
      receptor substrate (IRS)-1, a docking protein that is important for IGF1
      signaling, compromised hormone-induced mitosis in the uterine epithelium; BrdU
      incorporation was not affected. This selective effect on mitosis was associated
      with a reduction in uterine cyclin B-associated kinase activity; cyclin A
      associated kinase activity was not changed. The null mutation also reduced the
      extent of hormone-induced phosphorylation of endogenous uterine histone H1, as
      determined with phospho-specific antiserum. Uterine epithelial cyclin dependent
      kinase (cdk)1 was induced in response to hormone, but the level of the kinase
      protein, as determined by immunoblotting, was noticeably less in the irs1 null
      mutant than that in the wild-type (WT) mouse, especially around the time of peak
      mitosis (24 h). Since IRS-1 binds/activates phosphatidylinositol 3-kinase (PI3K),
      the absence of this docking protein could impair signaling of a known pathway
      downstream of AKT that stimulates translation of cell cycle components. Indeed,
      we found that phosphorylation of uterine AKT (Ser473) in irs1 null mutants was
      less than that in WTs following treatment. Based on earlier studies, it is also
      possible that an IGF1/IRS-1/PI3K/AKT pathway regulates posttranslational changes
      in cdk1. This model may provide insights as to how a growth factor pathway can
      mediate hormone action on cell proliferation.

PMID- 20798133
TI  - A case of chronic progressive myelopathy.
AB  - Acute myelitis and optic neuritis are the main clinical features of patients with
      neuromyelitis optica (NMO), which usually appears as a relapsing-remitting course
      of disease that worsens over days and improves over weeks. We present a patient
      with chronic progressive myelitis over a 4-month period without remission as
      having a limited form of NMO that improved after plasmapheresis. Plasmapheresis
      may benefit patients with chronic progressive myelitis, which may be a
      manifestation of NMO, as well as those with a relapsing-remitting course of NMO.

PMID- 20798134
TI  - Antiviral immune response in patients with multiple sclerosis, healthy siblings
      and twins.

PMID- 20798135
TI  - A novel adaptive design strategy increases the efficiency of clinical trials in
      secondary progressive multiple sclerosis.
AB  - BACKGROUND: Adaptive seamless designs (ASDs) have been proposed to test multiple
      candidate compounds using an interim decision point which allows potentially
      effective therapies to be taken into the next design stage and to be assessed
      using a phase III outcome. OBJECTIVE: To determine whether ASDs are feasible in
      secondary progressive multiple sclerosis (SPMS) and to compare them with
      conventional trial designs. METHODS: We develop an innovative adaptive trial
      design for SPMS, which builds on recent developments in statistical methodology.
      A literature search and individual clinical datasets were used to inform a
      framework to run simulations to evaluate the proposed design. RESULTS: ASDs are
      feasible in SPMS with MRI informing an interim decision point and Expanded
      Disability Status Scale (EDSS) as the final disability endpoint. Furthermore ASDs
      are more efficient than conventional designs with sample size savings of up to
      40%. Sample sizes of 1000-1250 patients are sufficient to test up to four
      experimental treatments. Controlled recruitment is important to realize the full
      benefits of ASDs. CONCLUSIONS: Although more complex in design, ASDs have the
      potential to be more efficient and more powerful than conventional designs.

PMID- 20798136
TI  - Dealing with pericardial suction blood and residual pump volume: a review of
      current practices in the UK.
AB  - The pathological effects of pericardial suction blood (PSB) have been well
      described in numerous studies for many years; yet, despite this, there is no
      definitive answer to the question of how best to attenuate this pathology. More
      recently, large studies have shown that, whilst PSB contains many factors
      indicating its pathological potential, the direct re-infusion of PSB and residual
      pump volume (RPV) after cardiopulmonary bypass (CPB) potentially reduces the risk
      of transfusion and is no more harmful to the patient than the re-infusion of cell
      salvage-processed PSB after CPB.We conducted a telephone audit of UK perfusion
      units to determine if current protocols and practices reflected this.We found
      that there is a definite majority processing RPV with cell-saving devices, with
      many units defining their protocols as "surgeon dependent" whilst half
      immediately returned PSB to the systemic circulation whilst on CPB. The results
      of this national audit suggest that the issue of dealing with PSB and RPV is
      confused, heavily influenced by surgical and anaesthetic preference and lacking
      clear guidance and high quality evidence.

PMID- 20798137
TI  - Clinical characteristics and prognosis of diffuse proliferative lupus nephritis
      with thrombotic microangiopathy.
AB  - We retrospectively analyzed the clinicopathologic characteristics and prognosis
      of 33 patients with diffuse proliferative lupus nephritis (class IV LN)
      complicated with thrombotic microangiopathy (TMA). Eighty-one percent of patients
      had renal dysfunction (mean Scr 3.1 +/- 2.0 mg/dl), among whom 42.4% needed acute
      hemodialysis. Nephrotic proteinuria, gross hematuria and hypertension were
      presented in 57.6%, 24.2% and 93.9% of the patients. Microangiopathic hemolytic
      anemia, serum anti-dsDNA and anticardiolipin antibodies were found in 60.6%,
      75.8% and 33.3% of the patients. Renal biopsy showed IV-G in 75.8%, class IV with
      class V in 21.2%, and IV-S in 1.23% of the patients. Glomerular segmental
      necrosis, microthrombi, crescents and arteriolar thrombosis were found in 51.5%,
      69.7%, 60.6% and 60.7% of the patients, respectively. The follow up was 1 to 101
      months (median 13 months). Only 50% of patients showed response to treatment.
      Three patients died, 10 developed end-stage renal failure (ESRF). The 5-year
      patient and renal survival rate was 69.2% and 46.7%, respectively. Major risks
      for ESRF included: a need for acute dialysis on admission, no response to the
      treatment and high renal chronic index. The results showed that class IV lupus
      nephritis with TMA has high mortality and low renal survival.

PMID- 20798138
TI  - Elevated evolutionary rate in genes with homopolymeric amino acid repeats
      constituting nondisordered structure.
AB  - Homopolymeric amino acid repeats are tandem repeats of single amino acids. About
      650 genes are known to have repeats of this kind comprising seven residues or
      more in the human genome. According to the evolutionary conservativeness, we
      classified the repeats into three categories: those whose length is conserved
      among mammals (CM), those whose length differs among nonprimate mammals but is
      conserved among primates (CP), and those whose length differs among primates
      (VP). The frequency of each repeat, especially Ala, Leu, Pro, and Glu repeats,
      varies greatly in each category. The 3D structure of homopolymeric amino acid
      repeats is considered to be intrinsically disordered. As expected, a large
      proportion of the repeats had a disordered structure, and nearly half of the
      repeats were predicted as completely disordered. However, a number of the repeats
      predicted to have nondisordered structure: 13% and 25% of the repeats for
      categories CM and VP, respectively. Comparison of the substitution rates showed a
      higher Ka/Ks ratio for the genes with not disordered repeats than the genes with
      disordered repeats. These results indicate that amino acid substitution rates
      have been elevated in the genes with nondisordered repeats.

PMID- 20798139
TI  - A comprehensive functional analysis of ancestral human signal peptides.
AB  - With the sequencing of the Neandertal genome, it has become possible to identify
      amino acid substitutions that occurred on the human lineage since its separation
      from the Neandertal lineage. Conceptually, it will therefore be possible to
      functionally analyze all such amino acid substitutions in the future. Here, we
      analyze the function of substitutions that occurred during recent human evolution
      in N-terminal signal peptides. We develop a high-throughput flow cytometry-based
      assay to analyze signal peptide efficiency as the ratio of surface to total
      reporter protein per live cell. Such ratios differed significantly among signal
      peptides derived from different human genes. However, no modern human signal
      peptide differed significantly from its ancestral counterpart, an observation
      compatible with the predictions of the neutral theory of molecular evolution.

PMID- 20798140
TI  - Men, food, and prostate cancer: gender influences on men's diets.
AB  - Although healthy eating might enhance long-term survival, few men with prostate
      cancer make diet changes to advance their well-being. Men's typically poor diets
      and uninterest in self-health may impede nutrition interventions and diet change.
      Food choice behavior is complex involving many determinants, including gender,
      which can shape men's health practices, diets, and prostate cancer experiences.
      Developing men-centered prostate cancer nutrition interventions to engage men
      (and where appropriate their partners) in promoting healthy diets can afford
      health benefits. This article presents an overview and synthesis of current
      knowledge about men's food practices and provides an analysis of diet and diet
      change behaviors for men with prostate cancer. Masculinity and gender relations
      theory are discussed in the context of men's food practices, and suggestions for
      future applications to nutrition and prostate cancer research and diet
      interventions are made.

PMID- 20798141
TI  - Letter to the editor: factors affecting men's health in Iran.

PMID- 20798142
TI  - "It used to be that if it weren't broken and bleeding profusely, I would never go
      to the doctor": men, masculinity, and health.
AB  - Masculine gender scripts have been influential in health decision making in men.
      In addition, although past research has identified some success in using churches
      as sites for health education with women, little is known if similar programs
      would be successful with men. It is also unclear if religious beliefs influence
      the health attitudes and behaviors of men. Four focus groups with men from four
      religious denominations were conducted to learn about their health beliefs,
      attitudes, and behaviors, with the following themes emerging: men's health fears,
      health promotion behaviors, spousal influence, aging and men's health, and church
      based health influence. Finally, the interaction of masculine gender scripts
      within these themes was considered.

PMID- 20798143
TI  - Personality and symptoms of psychological ill health among adult male offenders.
AB  - The current study investigated the relationship between personality and symptoms
      of psychological ill health in adult male offenders. Male offenders (N = 161)
      housed at two medium-high-risk institutions completed the Ten Item Personality
      Inventory and the Symptom Checklist Outpatient Rating Scale. Emotional stability
      emerged as the strongest individual predictor of psychological ill health and
      predicted each of the subscales measured (somatization, obsessive-compulsive,
      interpersonal sensitivity, depression, anxiety, anger-hostility, phobic anxiety,
      paranoid ideation, and psychoticism) and overall symptoms. Although agreeableness
      predicted depression and anger-hostility only, extraversion, conscientiousness,
      and openness to experience did not predict any aspect of psychological ill health
      investigated. The findings contribute to the current literature and provide
      further information about the relationship between personality and symptoms of
      psychological ill health in adult male offenders.

PMID- 20798144
TI  - Internet advertisements for public sexual encounters among men who have sex with
      men: are safe behaviors communicated?
AB  - Public and commercial sex venues typically provide easy access to sexual
      encounters that are often anonymous and, therefore, may facilitate HIV/STD
      transmission among those men who attend. Recently, researchers have suggested
      that men who have sex with men may be using the Internet to search for sexual
      encounters to occur within sex venues. The current study explored the extent to
      which men who advertise for public or commercial sexual encounters initially
      communicate to potential partners their safe-sex intentions. Advertisements for
      sexual encounters (n = 99) were collected from a publicly accessible website and
      examined for content related to venue type, sexual behavior, and indications of
      sexual safety or risk. Word frequencies were calculated to provide a closer
      investigation of how individuals negotiate safe sex within these communications.
      The findings revealed that approximately half of the men who advertised for sex
      in a public or commercial sex venue failed to communicate to potential partners
      in their initial advertisement a desire to be safe during sexual encounters
      involving oral and anal practices. Additionally, a small percentage of men
      advertised specifically for risky encounters (e.g., barebacking). Together, these
      findings suggest that men do use the Internet to coordinate public sexual
      encounters, some of which may be unprotected from HIV/STD transmission. Future
      research should address the process of condom negotiation among men who initially
      meet their male sex partners on the Internet for subsequent encounters in sex
      venues.

PMID- 20798145
TI  - Exploring body image and self-concept of men with acquired spinal cord injuries.
AB  - Qualitative research has rarely explored gender-based concerns of men with
      disabilities. Accordingly, this research investigates body image and self-concept
      for men with an acquired spinal cord injury (SCI). Modified grounded theory
      analysis was conducted for secondary, qualitative interview data of 64 male
      participants from a study of community dwellers living with SCI. Three major
      themes related to body image and self-concept emerged: consequences for self due
      to bodily changes, interactions with the public, and decisions and actions people
      take. Findings indicate that rehabilitation services should include ongoing
      research to explore the unique needs of male clients. Findings also have
      implications for rehabilitation therapists and their roles in addressing gender
      based concerns of the male client.

PMID- 20798146
TI  - Having a primary care provider and receipt of recommended preventive care among
      men in New York City.
AB  - To assess the role of having a primary care provider (PCP) in men's up-to-date
      receipt of recommended preventive services (colonoscopy, pneumococcal and
      seasonal influenza vaccination, cholesterol and blood pressure screenings), data
      from the 2005 and 2006 New York City Community Health Surveys (N = 3,728 [2006],
      2,810 [2005]) were analyzed. PCP prevalence and men's uptake of each service,
      overall and by age, race/ethnicity, education, income, insurance status, marital
      status, and nativity, were evaluated. After controlling for insurance status and
      other factors, having a PCP significantly predicted receipt of each service
      (adjusted prevalence ratio from 1.12 [1.08, 1.16] to 1.72 [1.35, 2.22]) and total
      services. Colonoscopy and seasonal influenza and pneumococcal vaccination receipt
      were below 70% with or without a PCP. Efforts to increase the proportion of men
      having a PCP are needed to improve receipt of recommended services. Maximizing
      awareness and provision of low-use preventive services may be useful.

PMID- 20798147
TI  - Men's experiences of living with osteoporosis: focus group interviews.
AB  - Osteoporotic fractures in men are an increasing public health problem. Male
      osteoporosis is often a low-prioritized issue, however. To examine men's
      experiences with osteoporosis and how they handle osteoporosis in their everyday
      lives, the authors collected data from four focus groups with a total of 16 men
      aged 51 to 82 years diagnosed with osteoporosis. Critical psychology was used as
      a theoretical framework for the data analysis, which aimed to elicit information
      about the men's daily lives. The men handled osteoporosis in different ways using
      different strategies. The authors found patterns that resonated with the social
      construction of hegemonic masculinity as displayed through the men's fear of
      weakness and endurance through physical activity, as well as identity
      construction through active decision making in relation to health. Understanding
      and implementation of these issues is necessary in the development of preventive,
      screening, and monitoring strategies, as well as in the clinical care of men with
      osteoporosis.

PMID- 20798148
TI  - Ethnicity as a factor in reproductive health care utilization among males
      attending family planning clinics.
AB  - Health care utilization of reproductive health care services among males is an
      emerging issue. This study examined ethnicity as a factor in reproductive health
      care utilization among 1,606 African American and Hispanic young males attending
      family planning clinics. Seventy percent were African American and 30% were
      Hispanic. Across groups, the most received service was treatment for a sexually
      transmitted infection (STI). African American males were more likely than
      Hispanic males to have health insurance, report a prior visit to a family
      planning/STI clinic, and have a history of an STI. Hispanic males had higher
      rates of employment. The most common source of referral for family planning
      services for both groups was either a current girlfriend or female friend.
      Hispanic males were more likely to use family as a referral source than African
      American males. Differences were also noted in regard to interest in health
      topics with African American males most interested in STI prevention and getting
      a job and Hispanic males in services related to working-out/eating well,
      controlling anger, feeling depressed, and getting along with family. Young males'
      perceptions of what they consider to be important health care needs should be
      assessed carefully in order to maintain their interest in returning to the
      clinics.

PMID- 20798150
TI  - Online sex-seeking behaviors of men who have sex with men in New York City.
AB  - The ongoing HIV epidemic among men who have sex with men (MSM) in New York City
      and the increased use of Internet sexual social networking websites by MSM
      fosters a need to understand the characteristics and sex-related behaviors of
      this group. The authors conducted an online survey of 195 MSM who use sexual
      social networking websites in New York City. Demographic characteristics, sexual
      sensation seeking, and HIV optimism-skepticism were compared among participants
      reporting sex with and without condom use (safe sex and high-risk sex,
      respectively) with partners met online. There was no difference in income,
      education, race, or employment status between the groups. The groups differed
      significantly in age, sexual sensation seeking, and HIV optimism-skepticism. In a
      multivariate logistic regression both HIV optimism-skepticism (p < .05) and
      sexual sensation seeking (p < .05) were significant predictors of high-risk
      sexual behavior (pseudo-R(2) = .24). This information should be considered when
      developing interventions for this group. For example, to reach those with high
      sexual sensation seeking, public health professionals should design sex-positive
      prevention messages for online distribution that highlight safer sex without
      condemning risky sexual practices.

PMID- 20798149
TI  - HPV vaccine acceptability in heterosexual, gay, and bisexual men.
AB  - We know little about men's beliefs about human papillomavirus (HPV) vaccine and
      willingness to receive it. In January 2009, the authors recruited 296
      heterosexual men and 312 gay and bisexual men from a national panel of U.S.
      households to complete an online survey about HPV and HPV vaccine. The authors
      analyzed data using logistic regression, controlling for age, education, number
      of lifetime sexual partners, and urban residence. More gay and bisexual men than
      heterosexual men were willing to receive HPV vaccine (73% vs. 37%; adjusted odds
      ratio = 4.99; 95% confidence interval = 3.36, 7.49). Gay and bisexual men
      reported greater awareness of HPV vaccine, perceived worry about HPV-related
      diseases, perceived effectiveness of HPV vaccine, and anticipated regret if they
      declined vaccination and later developed HPV-related disease compared with
      heterosexual men (all ps < .05). The lower acceptability and different beliefs
      among heterosexual men suggest that novel interventions for this group may be
      needed.

PMID- 20798152
TI  - Exploring relationships among psychosocial status, dietary quality, and measures
      of placental development during the first trimester in low-income women.
AB  - PURPOSE: To examine the relationships between maternal psychosocial factors and
      dietary quality and explore the relationships among dietary quality and selected
      biomarkers of nutrition and placental development. METHOD: A cross-sectional
      design in 18 low-income, pregnant women. RESULTS: Partner support was positively
      related to vegetable intake (r = .54) and negatively related to intake of iron (r
      = -.68) and grains (r = -.67). Emotional eating in response to anger was
      negatively related to intake of iron-(r /it> = -.53) and folate-rich (r = -.75)
      foods, and emotional eating in response to anxiety was negatively related to
      intake of folate-rich foods (r = -.51). Depressed women had an increased intake
      of calcium-rich foods (r = .60). Levels of vascular endothelial growth factor
      (VEGF) were negatively related to depression (r = -.56) and intake of foods high
      in calcium (r = -.53) and iron (r = -.34) but positively related to serum calcium
      levels (r = .60). VEGF was negatively relationship to soluble fms-like tyrosine
      kinase 1 (sFlt-1; r = -.56). Placental growth factor had a negative relationship
      with maternal serum levels of albumin (r = -.61) and calcium (r = -.65).
      CONCLUSIONS: Low-income pregnant women who eat to cope with anger and anxiety may
      have an inadequate intake of nutrients that contribute to positive pregnancy
      outcomes. Placental development in the early weeks of pregnancy may be influenced
      by maternal psychosocial and nutritional status. More research is needed to
      explore the relationship of dietary quality and placental development in the
      first trimester of pregnancy.

PMID- 20798151
TI  - Introduction to genetics and childhood obesity: relevance to nursing practice.
AB  - PURPOSE: The aims for this article are to provide an overview of the current
      state of research on genetic contributions to the development of childhood
      obesity and to suggest genetic-focused nursing practices to prevent childhood
      obesity. ORGANIZING CONSTRUCTS: Genetic epidemiology of childhood obesity, modes
      to identifying obesity genes, types of human obesity genes, and nursing
      implications are discussed. CLINICAL RELEVANCE: The successful integration of
      genetics into nursing practice will provide opportunities for nurses to
      participate fully as major agents and collaborators in the health care
      revolution. CONCLUSIONS: Practicing nurses across the profession will need to
      become knowledgeable about genetics and take part in obesity prevention through
      genetic assessment of susceptibility and appropriate environmental interventions.

PMID- 20798154
TI  - The effects of exercise conditioning in normal and overweight pregnant women on
      blood pressure and heart rate variability.
AB  - Pre-pregnancy obesity is a risk factor for preeclampsia, gestational diabetes,
      and hypertension. Regular exercise during pregnancy has been shown to decrease
      the risk of these obstetrical complications. The purpose of this prospective
      study was to measure the effects of an exercise program in normal-weight and
      overweight/obese pregnant women on blood pressure (BP) and cardiac autonomic
      function, determined by heart rate variability (HRV) and baroreflex sensitivity
      (BRS). Twenty-two sedentary pregnant women, recruited at 20 weeks gestational age
      (GA), were grouped as normal weight or overweight/obese. They were systematically
      assigned to an exercise (walking) group or control (nonwalking) group after the
      first participants were randomly assigned. Women in the walking groups
      participated in a 16-week, low-intensity walking program. BP, HRV, and BRS were
      measured at rest and during exercise at the beginning (20 weeks GA) and end (36
      weeks GA) of the walking program. Results indicated that women in the control
      groups (especially overweight women) showed changes in BP, HRV, and BRS over
      pregnancy that were not seen in the walking group. Overweight women in the
      control group increased resting systolic BP by 10 mmHg and diastolic BP by 7
      mmHg. HRV declined in the control group but not in the walking group. A reduction
      in BRS and R-R interval at rest was found in all groups except the walking normal
      weight group. The results suggest that an exercise program could attenuate the
      increase in BP and the loss of parasympathetic tone associated with pregnancy,
      especially in overweight women.

PMID- 20798153
TI  - Methodologic issues in the measurement of cytokines to elucidate the biological
      basis for cancer symptoms.
AB  - Multiple concurrent symptoms are highly prevalent in patients with cancer.
      However, little is known about the relationships among these symptoms and their
      underlying mechanisms. A number of cytokines that are involved in the development
      of sickness behavior are hypothesized to be a mechanism for symptom clusters.
      Measurement of these cytokines would provide valuable information that could be
      used to elucidate mechanisms underlying the development of symptom clusters and
      the identification of potential targets for intervention studies. In this
      article, the authors explore several issues that warrant careful consideration
      when designing a research study involving the use of a cytokine as a biomarker in
      symptom cluster research. These issues include which molecules to measure, which
      specimens to collect, the timing of specimen collection and processing, and which
      technologies to use to measure the biomarker and the sensitivity and specificity
      of the assay system. The article begins with a brief discussion of cytokines and
      sickness behavior and the role of the cytokines in cancer-related symptoms.

PMID- 20798156
TI  - Gendered innovations: a new approach for nursing science.
AB  - Considerable sex and gender bias has been recognized within the field of
      medicine. Investigators have used sex and gender analysis to reevaluate studies
      and outcomes and generate new perspectives and new questions regarding
      differential diagnoses and treatments of men and women. Sex and gender analysis
      acts as an experimental control to provide critical scientific rigor; researchers
      who ignore it risk ignoring a possible source of error in past, current, and
      future science. In this article, the authors introduce some tools of sex and
      gender analysis and illustrate the concept of gendered innovations by
      demonstrating through examples how this type of analysis has profoundly enhanced
      human knowledge in health and disease. The authors also provide recommendations
      for incorporating the concepts of sex and gender analysis into nursing education
      and research.

PMID- 20798155
TI  - Treatment of skin injury due to vinorelbine extravasation using bFGF and rhGM
      CSF: an experimental study in a murine model.
AB  - BACKGROUND AND OBJECTIVE: A murine model of skin injury from vinorelbine
      extravasation was established to evaluate the treatment efficacy of basic
      fibroblast growth factor (bFGF) and recombinant human granulocyte-macrophage
      colony-stimulating factor (rhGM-CSF). MATERIALS AND METHOD: Experimental models
      were divided into bFGF, rhGM-CSF, and control (saline) groups, with 40 mice in
      each group. Edema and ulceration were measured on Days 1, 3, 5, 7, 10, 14, and 18
      after the onset of extravasation; injuries were examined pathomorphologically in
      three mice/group/time point. RESULTS: Edema reached maximum size on Day 3 in the
      bFGF and rhGM-CSF groups and Day 5 in the control group. The difference between
      the two experimental groups was not significant; differences between the control
      group and the experimental groups were statistically significant at all time
      points. Edema and ulceration began to improve on Day 10 in the bFGF and rhGM-CSF
      groups and Day 18 in the control group. Healing duration was 14-18 days in the
      experimental groups, with a (not significantly) shorter duration in the bFGF
      group. Healing was completed by Day 27.5 in the control group. Pathomorphological
      evaluation showed regular re-epithelization and newly formed granulation tissue
      in the bFGF and rhGM-CSF groups on Day 13. In the control group, wounds were
      partially healed, edema and shallow ulcers existed, and epithelization was
      fragile and disorganized on Day 18. CONCLUSIONS: bFGF and rhGM-CSF are useful for
      the treatment of skin injury due to vinorelbine extravasation, but bFGF may be
      slightly more effective in decreasing time and improving quality of healing.

PMID- 20798158
TI  - Mother-infant activity synchrony as a correlate of the emergence of circadian
      rhythm.
AB  - OBJECTIVE: Entrainment to the day-night cycle is critical for infant sleep and
      social development. Synchronization of infant circadian systems with the social
      24-hr day may require maternal activity signals as an entraining cue. This
      descriptive and exploratory research examines the activity level and circadian
      pattern in mothers and infants. METHOD: Twenty-two healthy mothers and their
      infants (postnatal age 49.8 +/- 17.1 days) wore actigraph monitors for seven
      days. Daytime (06:00-21:59) and nighttime (22:00-05:59) activity levels and
      circadian parameters of rest-activity patterns (i.e., mesor, amplitude,
      acrophase, and 24-hr cosinor fit) were calculated. RESULTS: Mothers and infants
      were significantly more active during the day than at night. The goodness-of-fit
      index for the model (R2) indicates that circadian rhythm accounted for a mean of
      29 +/- 10% and 12 +/- 8% of the variability in maternal and infant activity,
      respectively. Acrophase of activity occurred at 15:46 +/- 1:07 for the mothers
      and 15:20 +/- 1:21 for the infants. The mean within-dyad correlation of activity
      counts was r = .46 +/- .11, and the within-dyad correlation was associated with
      the amplitude (r = .66, p < .01) and 24-hr cosinor fit of infant activity (r =
      .67, p < .01). CONCLUSIONS: Our findings suggest maternal rhythms as a possible
      exogenous influence on shaping an infant's emerging rhythms and synchronizing
      them with the external light-dark cycle. Strong pattern synchrony between
      maternal and infant activity may support infant circadian entrainment and enhance
      a regular 24-hr sleep-wake schedule during the early postnatal weeks.

PMID- 20798157
TI  - Maternal coping style and perceived adequacy of income predict CRH levels at 14
      20 weeks of gestation.
AB  - OBJECTIVE: This exploratory study examines the role of psychosocial-behavioral
      variables as predictors of elevated corticotropin-releasing hormone (CRH) at 14
      20 weeks of gestation. METHOD: One hundred and twenty women were enrolled into
      the study. Blood samples were collected at 14-20 weeks of pregnancy and assayed
      for CRH. Participants completed questionnaires that included the Perceived Stress
      Scale, the Center for Epidemiologic Studies (CES) Depression Scale, the Pregnancy
      Specific Anxiety (PAS) Scale, the Norbeck Social Support Questionnaire, the Life
      Orientation Test, the Brief COPE scale, and questions regarding violence/abuse,
      and work, sleep, and nutritional patterns. RESULTS: Pregnant women with high CRH
      levels (15 pcg/ml and above) perceived their income to be inadequate, slept more
      hours at night, stood more hours during the day, and used the coping styles of
      disengagement or religion but not humor. Logistic regression identified three
      predictors for high CRH (accounting for 42.2% of the variance): perceived
      inadequacy of income and the use of ''religion'' and ''disengagement'' to cope
      with stress. CONCLUSIONS: These results are the first known to identify coping
      style and perceived income inadequacy as predictors of high CRH. Women with
      perceived inadequacy of income had almost three times the odds for high CRH.
      Women who used religion or disengagement to cope with stress had 14 times and 7
      times the odds for high CRH levels, respectively. Higher CRH levels are
      associated with preterm birth (PTB). Thus, it may be important to include
      maternal coping style and perceptions of income inadequacy in future
      investigations of CRH levels and PTB.

PMID- 20798159
TI  - Antepartum bed rest for pregnancy complications: efficacy and safety for
      preventing preterm birth.
AB  - Preterm birth is the major maternal-child health issue across developed nations
      and the leading cause of perinatal mortality and morbidity. Of all deaths of
      infants <1 year of age in the United States in 2005, 68.6% occurred in infants
      born prior to term. Although the preterm birth rate in European countries is 5
      7%, the U.S. preterm birth rate is 12.7%, representing an increase of 9% since
      2000. Antepartum bed rest/activity restriction (ABR/AR) has been a mainstay of
      treatment to prevent preterm birth for the past 30 years prescribed for nearly 1
      million women in the United States annually, despite a lack of evidence for its
      effectiveness. In fact, there is increasing evidence that ABR causes several
      adverse physiologic and psychological side effects among women and their infants.
      Unfortunately, these findings have had little impact on clinical practice. This
      integrative review of literature provides a comprehensive analysis of the
      evidence for the practice of prescribing ABR and its physiologic, behavioral, and
      experiential side effects. It also presents a model to guide continuing research
      about the effects of maternal bed rest as well as evidence supporting the use of
      home care with bed rest, a different, safe, and feasible model of prenatal care
      for treating women with pregnancy complications used particularly in other
      countries. Finally, suggestions to improve the health of high-risk pregnant and
      postpartum women and their infants are provided.

PMID- 20798160
TI  - Health across generations: findings from the Australian Longitudinal Study on
      Women's Health.
AB  - Interpretation of changes in health and health care utilization patterns across
      the life span depends on an understanding of the effects of age, period, and
      cohort. The purpose of this article is to illustrate differences among three
      generations of women in demographic factors, health risk factors, and health
      status indicators from 1996 to 2008. The article examines data from the
      Australian Longitudinal Study on Women's Health, a broad-ranging project funded
      by the Australian Government Department of Health and Ageing (DoHA) and involving
      three age groups of women (born in the periods 1973-1978, 1946-1951, and 1921
      1926) who were first surveyed in 1996 and will be surveyed every 3 years until at
      least 2015. Patterns in selected demographic factors (marital status and level of
      educational qualification), health risk factors (smoking, alcohol consumption,
      physical activity, and body mass index [BMI]), and health status indicators
      (asthma, hypertension, diabetes and depression; physical functioning and mental
      health scores from the SF-36) were examined to illustrate examples of biological
      age, generational differences, or period effects that affect all age groups and
      generations simultaneously. The results can be used to inform the development of
      responsive and effective models for both prevention and management of chronic
      disease, including health and aged-care systems that will meet the needs of
      different generations of women across their life span.

PMID- 20798161
TI  - A call to action for evidence-based military women's health care: developing a
      women's health research agenda that addresses sex and gender in health and
      illness.
AB  - Women in the Army, Navy, Air Force, and Marines are serving in complex
      occupational specialties that sustain national policy and ensure combat
      effectiveness of our forces. Their roles have evolved from supportive roles
      during early conflicts to active roles in combat support and counterinsurgency
      operations today. Although women have received military health care over the past
      three decades, sex- and gender-specific care has been limited to reproductive
      needs and has rarely addressed military-specific health risks and outcomes. The
      complexity of military jobs and increased deployments to combat operations has
      led to increased occupational and health risks for women. As differences have
      been noted between men and women's deployment-related health outcomes, it is
      incumbent on the Military Health Care System (MHS) to create an evidence base
      that addresses sex and gender differences in the health of its service members. A
      working group of military women's health advanced practice nurses (APN) and
      research experts proposes to address this gap in knowledge and practices through
      sex- and gender-specific research. A sex-and gender-based research agenda for
      military women's health will be a valuable instrument to those who are dedicated
      to the health of this population, including members of the Army, Navy, and Air
      Force military nursing community. Using the knowledge that the research agenda
      generates, military health care providers can develop clinical practice
      guidelines, influence policy, and participate in program development to improve
      the health of servicewomen. Shaping a sex- and gender-specific military women's
      health research agenda will create the foundation for future evidence-based care.

PMID- 20798162
TI  - Antisense-RNA-mediated plasmid copy number control in pCG1-family plasmids, pCGR2
      and pCG1, in Corynebacterium glutamicum.
AB  - pCGR2 and pCG1 belong to different subfamilies of the pCG1 family of
      Corynebacterium glutamicum plasmids. Nonetheless, they harbour homologous
      putative antisense RNA genes, crrI and cgrI, respectively. The genes in turn
      share identical positions complementary to the leader region of their respective
      repA (encoding plasmid replication initiator) genes. Determination of their
      precise transcriptional start- and end-points revealed the presence of short
      antisense RNA molecules (72&emsp14;bp, CrrI; and 73&emsp14;bp, CgrI). These short
      RNAs and their target mRNAs were predicted to form highly structured molecules
      comprising stem-loops with known U-turn motifs. Abolishing synthesis of CrrI and
      CgrI by promoter mutagenesis resulted in about sevenfold increase in plasmid copy
      number on top of an 11-fold (CrrI) and 32-fold (CgrI) increase in repA mRNA,
      suggesting that CrrI and CgrI negatively control plasmid replication. This
      control is accentuated by parB, a gene that encodes a small centromere-binding
      plasmid-partitioning protein, and is located upstream of repA. Simultaneous
      deactivation of CrrI and parB led to a drastic 87-fold increase in copy number of
      a pCGR2-derived shuttle vector. Moreover, the fact that changes in the structure
      of the terminal loops of CrrI and CgrI affected plasmid copy number buttressed
      the important role of the loop structure in formation of the initial interaction
      complexes between antisense RNAs and their target mRNAs. Similar antisense RNA
      control systems are likely to exist not only in the two C. glutamicum pCG1
      subfamilies but also in related plasmids across Corynebacterium species.

PMID- 20798163
TI  - Role of Hcp, a type 6 secretion system effector, of Aeromonas hydrophila in
      modulating activation of host immune cells.
AB  - Recently, we reported that the type 6 secretion system (T6SS) of Aeromonas
      hydrophila SSU plays an important role in bacterial virulence in a mouse model,
      and immunization of animals with the T6SS effector haemolysin co-regulated
      protein (Hcp) protected them against lethal infections with wild-type bacteria.
      Additionally, we showed that the mutant bacteria deleted for the vasH gene within
      the T6SS gene cluster did not express the hcp gene, while the vasK mutant could
      express and translocate Hcp, but was unable to secrete it into the extracellular
      milieu. Both of these A. hydrophila SSU mutants were readily phagocytosed by
      murine macrophages, pointing to the possible role of the secreted form of Hcp in
      the evasion of the host innate immunity. By using the DeltavasH mutant of A.
      hydrophila, our in vitro data showed that the addition of exogenous recombinant
      Hcp (rHcp) reduced bacterial uptake by macrophages. These results were
      substantiated by increased bacterial virulence when rHcp was added along with the
      DeltavasH mutant in a septicaemic mouse model of infection. Analysis of the
      cytokine profiling in the intraperitoneal lavage as well as activation of host
      cells after 4&emsp14;h of infection with the DeltavasH mutant supplemented with
      rHcp indicated that this T6SS effector inhibited production of pro-inflammatory
      cytokines and induced immunosuppressive cytokines, such as interleukin-10 and
      transforming growth factor-beta, which could circumvent macrophage activation and
      maturation. This mechanism of innate immune evasion by Hcp possibly inhibited the
      recruitment of cellular immune components, which allowed bacterial multiplication
      and dissemination in animals, thereby leading to their mortality.

PMID- 20798165
TI  - Diversity of caecal bacteria is altered in interleukin-10 gene-deficient mice
      before and after colitis onset and when fed polyunsaturated fatty acids.
AB  - Interleukin-10 gene-deficient (Il10(-/-)) mice show a hyper-reaction to normal
      intestinal bacteria and develop spontaneous colitis similar to that of human
      Crohn's disease when raised under conventional (but not germ-free) conditions.
      The lack of IL10 protein in these mice leads to changes in intestinal metabolic
      and signalling processes. The first aim of this study was to identify changes in
      the bacterial community of the caeca at 7 weeks of age (preclinical colitis) and
      at 12 weeks of age (when clinical signs of colitis are present), and establish if
      there were any changes that could be associated with the mouse genotype. We have
      previously shown that dietary n-3 and n-6 polyunsaturated fatty acids (PUFA) have
      anti-inflammatory effects and affect colonic gene expression profiles in Il10(-/
      ) mice; therefore, we also aimed to test the effect of the n-3 PUFA
      eicosapentaenoic acid (EPA) and the n-6 PUFA arachidonic acid (AA) on the
      bacterial community of caeca in both Il10(-/-) and C57 mice fed these diets. The
      lower number of caecal bacteria observed before colitis (7 weeks of age) in Il10(
      /-) compared to C57 mice suggests differences in the intestinal bacteria that
      might be associated with the genotype, and this could contribute to the
      development of colitis in this mouse model. The number and diversity of caecal
      bacteria increased after the onset of colitis (12 weeks of age). The increase in
      caecal Escherichia coli numbers in both inflamed Il10(-/-) and healthy C57 mice
      might be attributed to the dietary PUFA (especially dietary AA), and thus not be
      a cause of colitis development. A possible protective effect of E. coli mediated
      by PUFA supplementation and associated changes in the bacterial environment could
      be a subject for further investigation to define the mode of action of PUFA in
      colitis.

PMID- 20798164
TI  - DevT (Alr4674), resembling a Ser/Thr protein phosphatase, is essential for
      heterocyst function in the cyanobacterium Anabaena sp. PCC 7120.
AB  - Heterocyst-forming cyanobacteria are able to perform oxygenic photosynthesis and
      nitrogen fixation simultaneously in the same filament, by restricting the highly
      O(2)-sensitive nitrogenase to specialized cells, the heterocysts. A remarkable
      change in morphology and metabolism accompanies the differentiation of
      heterocysts, which only occurs when no source of combined nitrogen is available.
      In this study, we characterized DevT (Alr4674), a putative protein phosphatase
      from Anabaena PCC 7120. Mutants defective in devT are able to form
      morphologically mature heterocysts, which however cannot fix N(2), and the mutant
      cannot survive without a source of combined nitrogen. DevT shows homology to
      phosphatases of the PPP family and displays a Mn(2+)-dependent phosphatase
      activity that can be inhibited by phosphatase inhibitors and oxidizing
      conditions. DevT is constitutively expressed in both vegetative cells and
      heterocysts, and is not regulated by NtcA. The heterocyst regulator HetR may
      exert a certain inhibition on the expression of devT. Under diazotrophic growth
      conditions, DevT protein accumulates specifically in mature heterocysts.
      Therefore DevT plays a still unknown role in a late essential step of heterocyst
      differentiation.

PMID- 20798166
TI  - Molecular characterization of plant acidic alpha-mannosidase, a member of
      glycosylhydrolase family 38, involved in the turnover of N-glycans during tomato
      fruit ripening.
AB  - It has been reported that acidic alpha-mannosidase activity increases during
      tomato fruit ripening, suggesting the turnover of N-glycoproteins is deeply
      associated with fruit ripening. As part of a study to reveal the relationship
      between the plant alpha-mannosidase activity and fruit maturation at the
      molecular level, we have already purified and characterized an alpha-mannosidase
      from tomato fruit (Hossain et al., Biosci. Biotechnol. Biochem. 2009;73:140-146).
      In this article, we describe the identification and expression of the tomato
      acidic alpha-mannosidase gene using the yeast-expression system. The alpha
      mannosidase-gene located at chomosome 6 is a 10 kb spanned containing 30 exons.
      The gene-encoded-protein is single polypeptide chain of 1,028 amino acids
      containing glycosyl hydrolase domain-38 with predicted molecular mass of 116 kDa.
      The recombinant enzyme showed maximum activity at pH 5.5, and was almost
      completely inhibited by both of 1-deoxymannojirimycin and swainsonine. The
      recombinant alpha-mannosidase, like the native enzyme, could cleave alpha1-2, 1-3
      and 1-6 mannosidic linkage from both high-mannose and truncated complex-type N
      glycans. A molecular 3D modelling shows that catalytically important residues of
      animal lysosomal alpha-mannosidase could be superimposed on those of tomato alpha
      mannosidase, suggesting that active site conformation is highly conserved between
      plant acidic alpha-mannosidase and animal lysosomal alpha-mannosidase.

PMID- 20798167
TI  - A revised biosynthetic pathway for phosphatidylinositol in Mycobacteria.
AB  - For the last decade, it has been believed that phosphatidylinositol (PI) in
      mycobacteria is synthesized from free inositol and CDP-diacylglycerol by PI
      synthase in the presence of ATP. The role of ATP in this process, however, is not
      understood. Additionally, the PI synthase activity is extremely low compared with
      the PI synthase activity of yeast. When CDP-diacylglycerol and [(14)C]1L-myo
      inositol 1-phosphate were incubated with the cell wall components of
      Mycobacterium smegmatis, both phosphatidylinositol phosphate (PIP) and PI were
      formed, as identified by fast atom bombardment-mass spectrometry and thin-layer
      chromatography. PI was formed from PIP by incubation with the cell wall
      components. Thus, mycobacterial PI was synthesized from CDP-diacylglycerol and
      myo-inositol 1-phosphate via PIP, which was dephosphorylated to PI. The gene
      encoding PIP synthase from four species of mycobacteria was cloned and expressed
      in Escherichia coli, and PIP synthase activity was confirmed. A very low, but
      significant level of free [(3)H]inositol was incorporated into PI in
      mycobacterial cell wall preparations, but not in recombinant E. coli cell
      homogenates. This activity could be explained by the presence of two minor PI
      metabolic pathways: PI/inositol exchange reaction and phosphorylation of inositol
      by ATP prior to entering the PIP synthase pathway.

PMID- 20798168
TI  - A progress report on electronic health records in U.S. hospitals.
AB  - Given the substantial federal financial incentives soon to be available to
      providers who make "meaningful use" of electronic health records, tracking the
      progress of this health care technology conversion is a policy priority. Using a
      recent survey of U.S. hospitals, we found that the share of hospitals that had
      adopted either basic or comprehensive electronic records has risen modestly, from
      8.7 percent in 2008 to 11.9 percent in 2009. Small, public, and rural hospitals
      were less likely to embrace electronic records than their larger, private, and
      urban counterparts. Only 2 percent of U.S. hospitals reported having electronic
      health records that would allow them to meet the federal government's "meaningful
      use" criteria. These findings underscore the fact that the transition to a
      digital health care system is likely to be a long one.

PMID- 20798169
TI  - METAREP: JCVI metagenomics reports--an open source tool for high-performance
      comparative metagenomics.
AB  - SUMMARY: JCVI Metagenomics Reports (METAREP) is a Web 2.0 application designed to
      help scientists analyze and compare annotated metagenomics datasets. It utilizes
      Solr/Lucene, a high-performance scalable search engine, to quickly query large
      data collections. Furthermore, users can use its SQL-like query syntax to filter
      and refine datasets. METAREP provides graphical summaries for top taxonomic and
      functional classifications as well as a GO, NCBI Taxonomy and KEGG Pathway
      Browser. Users can compare absolute and relative counts of multiple datasets at
      various functional and taxonomic levels. Advanced comparative features comprise
      statistical tests as well as multidimensional scaling, heatmap and hierarchical
      clustering plots. Summaries can be exported as tab-delimited files, publication
      quality plots in PDF format. A data management layer allows collaborative data
      analysis and result sharing. AVAILABILITY: Web site http://www.jcvi.org/metarep;
      source code http://github.com/jcvi/METAREP CONTACT: syooseph@jcvi.org
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 20798170
TI  - RDP3: a flexible and fast computer program for analyzing recombination.
AB  - RDP3 is a new version of the RDP program for characterizing recombination events
      in DNA-sequence alignments. Among other novelties, this version includes four new
      recombination analysis methods (3SEQ, VISRD, PHYLRO and LDHAT), new tests for
      recombination hot-spots, a range of matrix methods for visualizing over-all
      patterns of recombination within datasets and recombination-aware ancestral
      sequence reconstruction. Complementary to a high degree of analysis flow
      automation, RDP3 also has a highly interactive and detailed graphical user
      interface that enables more focused hands-on cross-checking of results with a
      wide variety of newly implemented phylogenetic tree construction and matrix-based
      recombination signal visualization methods. The new RDP3 can accommodate large
      datasets and is capable of analyzing alignments ranging in size from 1000 * 10
      kilobase sequences to 20 * 2 megabase sequences within 48 h on a desktop PC.
      AVAILABILITY: RDP3 is available for free from its web site
      http://darwin.uvigo.es/rdp/rdp.html.

PMID- 20798171
TI  - Measuring the physical cohesiveness of proteins using physical interaction
      enrichment.
AB  - MOTIVATION: Protein-protein interaction (PPI) networks are a valuable resource
      for the interpretation of genomics data. However, such networks have interaction
      enrichment biases for proteins that are often studied. These biases skew
      quantitative results from comparing PPI networks with genomics data. Here, we
      introduce an approach named physical interaction enrichment (PIE) to eliminate
      these biases. METHODOLOGY: PIE employs a normalization that ensures equal node
      degree (edge) distribution of a test set and of the random networks it is
      compared with. It quantifies whether a set of proteins have more interactions
      between themselves than proteins in random networks, and can therewith be
      regarded as physically cohesive. RESULTS: Among other datasets, we applied PIE to
      genetic morbid disease (GMD) genes and to genes whose expression is induced upon
      infection with human-metapneumovirus (HMPV). Both sets contain proteins that are
      often studied and that have relatively many interactions in the PPI network.
      Although interactions between proteins of both sets are found to be
      overrepresented in PPI networks, the GMD proteins are not more likely to interact
      with each other than random proteins when this overrepresentation is taken into
      account. In contrast the HMPV-induced genes, representing a biologically more
      coherent set, encode proteins that do tend to interact with each other and can be
      used to predict new HMPV-induced genes. By handling biases in PPI networks, PIE
      can be a valuable tool to quantify the degree to which a set of genes are
      involved in the same biological process.

PMID- 20798172
TI  - Pre-existing arterial stiffness can predict hypotension during induction of
      anaesthesia in the elderly.
AB  - BACKGROUND: The aim of the present study was to establish whether elevated
      carotid-femoral pulse wave velocity (c-fPWV), an indicator of aortic stiffness,
      assessed before surgery, is correlated with variations in arterial pressure (AP)
      during induction of anaesthesia in elderly patients undergoing non-cardiovascular
      surgery. METHODS: c-fPWV was measured with the PulsePen((r)) device during pre
      surgical anaesthetic evaluation. Monitoring included electrocardiography, pulse
      oximetry, non-invasive AP, heart rate, bispectral index (BIS), and oxygen
      concentration during induction of anaesthesia with propofol and remifentanil.
      Anaesthesia was induced so as to maintain BIS values between 40 and 50. RESULTS:
      Forty-five patients, aged [mean (sd)] 71.1 (5.8) yr, were studied. The mean value
      of c-fPWV was 12.1 (3.9) m s-1. There was no correlation between hypotension
      during anaesthesia induction and total dosage or rate of administration of
      propofol or remifentanil. In univariate analysis, only age and PWV significantly
      correlated with the decreases in AP, and the association between c-fPWV and a
      decrease in AP was also seen in multivariate analysis (r = 0.36, P< 0.05).
      Patients classified as having 'high stiffness' (c-fPWV >= 12.9 m s-1) had 25%
      further decrease in systolic AP during anaesthesia induction than those with
      lower PWV [75.2 (5.7) vs 60.2 (4.2) mm Hg, P < 0.05]. CONCLUSIONS: Increased
      aortic stiffness, as assessed by PWV measured during preoperative anaesthetic
      evaluation, is associated with more pronounced hypotension during induction of
      anaesthesia. Measurement of aortic stiffness in the elderly may thus represent a
      valid indicator of the risk of hypotension during anaesthesia induction.

PMID- 20798173
TI  - A fast, efficient and sequence-independent method for flexible multiple segmental
      isotope labeling of RNA using ribozyme and RNase H cleavage.
AB  - Structural information on RNA, emerging more and more as a major regulator in
      gene expression, dramatically lags behind compared with information on proteins.
      Although NMR spectroscopy has proven to be an excellent tool to solve RNA
      structures, it is hampered by the severe spectral resonances overlap found in
      RNA, limiting its use for large RNA molecules. Segmental isotope labeling of RNA
      or ligation of a chemically synthesized RNA containing modified nucleotides with
      an unmodified RNA fragment have proven to have high potential in overcoming
      current limitations in obtaining structural information on RNA. However, low
      yields, cumbersome preparations and sequence requirements have limited its
      broader application in structural biology. Here we present a fast and efficient
      approach to generate multiple segmentally labeled RNAs with virtually no sequence
      requirements with very high yields (up to 10-fold higher than previously
      reported). We expect this approach to open new avenues in structural biology of
      RNA.

PMID- 20798174
TI  - Crucial contribution of the multiple copies of the initiator tRNA genes in the
      fidelity of tRNA(fMet) selection on the ribosomal P-site in Escherichia coli.
AB  - The accuracy of the initiator tRNA (tRNA(fMet)) selection in the ribosomal P-site
      is central to the fidelity of protein synthesis. A highly conserved occurrence of
      three consecutive G-C base pairs in the anticodon stem of tRNA(fMet) contributes
      to its preferential selection in the P-site. In a genetic screen, using a plasmid
      borne copy of an inactive tRNA(fMet) mutant wherein the three G-C base pairs were
      changed, we isolated Escherichia coli strains that allow efficient initiation
      with the tRNA(fMet) mutant. Here, extensive characterization of two such strains
      revealed novel mutations in the metZWV promoter severely compromising tRNA(fMet)
      levels. Low cellular abundance of the chromosomally encoded tRNA(fMet) allows
      efficient initiation with the tRNA(fMet) mutant and an elongator tRNA(Gln),
      revealing that a high abundance of the cellular tRNA(fMet) is crucial for the
      fidelity of initiator tRNA selection on the ribosomal P-site in E. coli. We
      discuss possible implications of the changes in the cellular tRNA(fMet) abundance
      in proteome remodeling.

PMID- 20798175
TI  - A yeast one-hybrid system to screen for methylated DNA-binding proteins.
AB  - We had previously exploited a method for targeted DNA methylation in budding
      yeast to succeed in one-hybrid detection of methylation-dependent DNA-protein
      interactions. Based on this finding, we developed a yeast one-hybrid system to
      screen cDNA libraries for clones encoding methylated DNA-binding proteins.
      Concurrent use of two independent bait sequences in the same cell, or dual-bait
      system, effectively reduced false positive clones, which were derived from
      methylation-insensitive sequence-specific DNA-binding proteins. We applied the
      dual-bait system to screen cDNA libraries and demonstrated efficient isolation of
      clones for methylated DNA-binding proteins. This system would serve as a unique
      research tool for epigenetics.

PMID- 20798176
TI  - The NIP7 protein is required for accurate pre-rRNA processing in human cells.
AB  - Eukaryotic ribosome biogenesis requires the function of a large number of trans
      acting factors which interact transiently with the nascent pre-rRNA and
      dissociate as the ribosomal subunits proceed to maturation and export to the
      cytoplasm. Loss-of-function mutations in human trans-acting factors or ribosome
      components may lead to genetic syndromes. In a previous study, we have shown
      association between the SBDS (Shwachman-Bodian-Diamond syndrome) and NIP7
      proteins and that downregulation of SBDS in HEK293 affects gene expression at the
      transcriptional and translational levels. In this study, we show that
      downregulation of NIP7 affects pre-rRNA processing, causing an imbalance of the
      40S/60S subunit ratio. We also identified defects at the pre-rRNA processing
      level with a decrease of the 34S pre-rRNA concentration and an increase of the
      26S and 21S pre-rRNA concentrations, indicating that processing at site 2 is
      particularly slower in NIP7-depleted cells and showing that NIP7 is required for
      maturation of the 18S rRNA. The NIP7 protein is restricted to the nuclear
      compartment and co-sediments with complexes with molecular masses in the range of
      40S-80S, suggesting an association to nucleolar pre-ribosomal particles.
      Downregulation of NIP7 affects cell proliferation, consistently with an important
      role for NIP7 in rRNA biosynthesis in human cells.

PMID- 20798178
TI  - Atypical presentation of pneumomediastinum with an unusual oesophageal aetiology.

PMID- 20798177
TI  - Verifying expressed transcript variants by detecting and assembling stretches of
      consecutive exons.
AB  - We herein describe an integrated system for the high-throughput analysis of
      splicing events and the identification of transcript variants. The system
      resolves individual splicing events and elucidates transcript variants via a
      pipeline that combines aspects such as bioinformatic analysis, high-throughput
      transcript variant amplification, and high-resolution capillary electrophoresis.
      For the 14 369 human genes known to have transcript variants, minimal primer sets
      were designed to amplify all transcript variants and examine all splicing events;
      these have been archived in the ASprimerDB database, which is newly described
      herein. A high-throughput thermocycler, dubbed GenTank, was developed to
      simultaneously perform thousands of PCR amplifications. Following the resolution
      of the various amplicons by capillary gel electrophoresis, two new computer
      programs, AmpliconViewer and VariantAssembler, may be used to analyze the
      splicing events, assemble the consecutive exons embodied by the PCR amplicons,
      and distinguish expressed versus putative transcript variants. This novel system
      not only facilitates the validation of putative transcript variants and the
      detection of novel transcript variants, it also semi-quantitatively measures the
      transcript variant expression levels of each gene. To demonstrate the system's
      capability, we used it to resolve transcript variants yielded by single and
      multiple splicing events, and to decipher the exon connectivity of long
      transcripts.

PMID- 20798179
TI  - Fall and balance outcomes after an intervention to promote leg strength, balance,
      and walking in people with diabetic peripheral neuropathy: "feet first"
      randomized controlled trial.
AB  - BACKGROUND: Weight-bearing exercise has been discouraged for people with diabetes
      mellitus and peripheral neuropathy (DM+PN). However, people with diabetes
      mellitus and insensate feet have an increased risk of falling. Lower-extremity
      exercise and balance training reduce fall risk in some older adults. It is
      unknown whether those with neuropathy experience similar benefits. OBJECTIVE: As
      part of a study of the effects of weight-bearing exercise on foot ulceration in
      people with DM+PN, the effects of a lower-extremity exercise and walking
      intervention on balance, lower-extremity strength (force-generating capacity),
      and fall incidence were determined. Design The study was an observer-masked, 12
      month randomized controlled trial. SETTING: Part 1 of the intervention took place
      in physical therapy offices, and part 2 took place in the community. PATIENTS:
      The participants were 79 people who were mostly sedentary, who had DM+PN, and who
      were randomly assigned to either a control group (n=38) or an intervention group
      (n=41). Intervention Part 1 included leg strengthening and balance exercises and
      a graduated, self-monitored walking program; part 2 included motivational
      telephone calls. Both groups received regular foot care, foot care education, and
      8 sessions with a physical therapist. MEASUREMENTS: The measurements collected
      were strength, balance, and participant-reported falls for the year after
      enrollment. RESULTS: There were no statistically significant differences between
      the groups for falls during follow-up. At 12 months, there was a small increase
      in the amount of time that participants in the intervention group could stand on
      1 leg with their eyes closed. No other strength or balance measurements differed
      between the groups. LIMITATIONS: The study was designed to detect differences in
      physical activity, not falls. The intensity of the intervention was insufficient
      to improve strength and balance in this population. CONCLUSIONS: The training
      program had a minimal effect on participants' balance and lower-extremity
      strength. Increasing weight-bearing activity did not alter the rate of falling
      for participants in the intervention group relative to that for participants in
      the control group. People who are sedentary and who have DM+PN appear to be able
      to increase activity without increasing their rate of falling.

PMID- 20798180
TI  - Use of physical therapy services among middle-aged and older adults with multiple
      sclerosis.
AB  - BACKGROUND: There is limited understanding of the utilization of and perceived
      need for physical therapy services among middle-aged and older adults with
      multiple sclerosis (MS). The resulting knowledge gap compromises efforts for
      physical therapy service planning for this population. OBJECTIVE: The purpose of
      this study was to examine the use of and need for physical therapy services in a
      sample of adults with MS living in the Midwestern United States. DESIGN: This was
      a cross-sectional, descriptive study. METHODS: Data from telephone interviews
      with 1,065 people with MS, aged 45 to 90 years, were used for the study. A
      multinomial regression model was used to determine factors associated with use of
      physical therapy services (never, within the past year, more than a year ago).
      Logistic regression analysis examined factors associated with unmet needs for
      these services. RESULTS: Thirty-six percent of the sample reported never using
      physical therapy services, 33% reported using physical therapy services within
      the past year, and 31% reported using physical therapy services more than a year
      prior to the interview. Factors associated with recent use of physical therapy
      services included living in an urban or suburban community, deteriorating MS
      status, experiencing problems with spasticity (ie, hypertonicity), having
      difficulty moving inside the house, being hospitalized in the past 6 months, and
      seeing a family physician. These same factors were associated with unmet needs.
      Limitations Physical therapy service use was self-reported. Data were collected
      in 5 Midwestern states from people 45 years of age or older, which may limit
      generalizability. CONCLUSIONS: Factors associated with use of and need for
      physical therapy services reflect issues of access (geographical, referrals), MS
      status, and mobility difficulties.

PMID- 20798181
TI  - OpenHelix: bioinformatics education outside of a different box.
AB  - The amount of biological data is increasing rapidly, and will continue to
      increase as new rapid technologies are developed. Professionals in every area of
      bioscience will have data management needs that require publicly available
      bioinformatics resources. Not all scientists desire a formal bioinformatics
      education but would benefit from more informal educational sources of learning.
      Effective bioinformatics education formats will address a broad range of
      scientific needs, will be aimed at a variety of user skill levels, and will be
      delivered in a number of different formats to address different learning styles.
      Informal sources of bioinformatics education that are effective are available,
      and will be explored in this review.

PMID- 20798182
TI  - Broader incorporation of bioinformatics in education: opportunities and
      challenges.
AB  - The major opportunities for broader incorporation of bioinformatics in education
      can be placed into three general categories: general applicability of
      bioinformatics in life science and related curricula; inherent fit of
      bioinformatics for promoting student learning in most biology programs; and the
      general experience and associated comfort students have with computers and
      technology. Conversely, the major challenges for broader incorporation of
      bioinformatics in education can be placed into three general categories: required
      infrastructure and logistics; instructor knowledge of bioinformatics and
      continuing education; and the breadth of bioinformatics, and the diversity of
      students and educational objectives. Broader incorporation of bioinformatics at
      all education levels requires overcoming the challenges to using transformative
      computer-requiring learning activities, assisting faculty in collecting
      assessment data on mastery of student learning outcomes, as well as creating more
      faculty development opportunities that span diverse skill levels, with an
      emphasis placed on providing resource materials that are kept up-to-date as the
      field and tools change.

PMID- 20798183
TI  - Reaction time variability in HIV-positive individuals.
AB  - Progression of HIV/AIDS is frequently associated with frontal/subcortical
      dysfunction and mean reaction time (RT) slowing. Beyond group means, within
      subject variability of RT has been found to be particularly sensitive to
      frontal/subcortical dysfunction in other populations. However, the possible
      relevance of RT variability to HIV/AIDS patients remains unknown. This study
      evaluated the relationships between RT variability and indicators such as
      neurocognitive, behavioral, and immunological status. A total of 46 HIV-positive
      adults on antiretroviral medication regimens were included in this study. Overall
      performance of this sample was poorer than normative means on measures of RT
      latency, RT variability, and traditional neurocognitive domains. Results
      demonstrated that the measures of RT variability were associated with global
      cognition, medication adherence rates, and peak immunological dysfunction, above
      and beyond the effects of RT latency. These preliminary findings suggest that
      measures of RT variability may provide enhanced sensitivity to neurocognitive
      disease burden in HIV/AIDS relative to more traditional measures of mean RT or
      cognitive function.

PMID- 20798185
TI  - Association of disease, adolescent, and family factors with medication adherence
      in pediatric inflammatory bowel disease.
AB  - OBJECTIVE: To examine factors associated with adolescent and parent-reported
      adherence to prescription and over-the-counter (OTC) medications in a cross
      sectional sample of youth with inflammatory bowel disease (IBD). METHOD: Ninety
      adolescents and their parents completed measures of medication adherence and
      disease, individual, and family factors while attending an outpatient
      gastroenterology appointment. RESULTS: Longer time since diagnosis, greater
      perceived disease severity, and a lack of autonomous motivation to adhere
      predicted adolescent report of lower adherence to prescription medications.
      Similarly, longer time since diagnosis predicted adolescent report of lower
      adherence to OTC medications. Less time since diagnosis, greater maternal
      involvement in the medical regimen, higher perceived disease severity, and less
      perceived conflict predicted better parent-reported adherence to OTC medications.
      CONCLUSIONS: Interventions for improving adherence in adolescents with IBD should
      address disease, individual, and family factors with special attention given to
      adolescents who have been diagnosed longer.

PMID- 20798184
TI  - Estimates of HIV incidence among drug users in St. Petersburg, Russia: continued
      growth of a rapidly expanding epidemic.
AB  - BACKGROUND: Russia has one of the world's fastest growing HIV epidemics and it
      has been largely concentrated among injection drug users (IDU). St Petersburg,
      Russia's second largest city, is one of the country's regions that has been most
      affected by the HIV epidemic. To monitor the current epidemic situation, we
      sought to estimate recent HIV incidence among IDU in St Petersburg. METHODS: In a
      cross-sectional study of 691 IDU recruited during 2005-08, HIV incidence was
      estimated by two methods: a retrospective cohort analysis and BED capture enzyme
      immunoassay (EIA) results. Socio-demographic and behavioural correlates of
      incident infections and spatial patterns were examined. RESULTS: In the
      retrospective cohort analysis, the incidence rate was estimated to be 14.1/100
      person-years [95% confidence interval (CI) 10.7-17.6]. Using results of BED EIA
      and two correction formulas for known misclassification, incidence estimates were
      23.9 (95% CI 17.8-30.1) and 25.5 (95% CI 18.9-32.0) per 100 person-years.
      Independent correlates of being recently infected included current unemployment
      (P = 0.004) and not having injected drugs in the past 30 days (P = 0.03). HIV
      incident cases were detected in all but one district in the city, with focal
      areas of transmission observed to be expanding. CONCLUSIONS: High HIV incidence
      among IDU in St Petersburg attests to continued growth of the epidemic. The need
      for expansion of HIV prevention interventions targeted to vulnerable populations
      throughout the city is urgent. These results also suggest that the BED EIA may
      over-estimate incidence even after correction for low specificity.

PMID- 20798186
TI  - Psychosocial considerations about children and radiological events.
AB  - Children are identified as a vulnerable population in the case of radiological
      events because of their increased physical sensitivity to radiation and its
      impact on critical development stages. Using a comprehensive integrated risk
      framework, psychosocial risk protective factors are discussed in a social ecology
      paradigm. Children have been shown to be both vulnerable and resilient; they are
      both easily impressionable and also quick to adapt and learn. Psychosocial
      interventions during, after and most efficiently before an event can improve
      outcome, especially if they involve parents and schools, media and work
      organisations. Public education through children should be encouraged to increase
      knowledge of radiation and strategies to minimise exposure and irradiation.
      Children can become vectors of prevention, preparedness and mitigation through
      information and behavioural rehearsal. Special consideration must therefore be
      given to education, school programmes, practice rehearsal and media exposure.

PMID- 20798187
TI  - Vulnerability of children: more than a question of age.
AB  - The vulnerability of children in disasters is well-established. Children are at
      greater risk of the impacts of disasters because of both their age and level of
      physiological, anatomical, cognitive and emotional development. Frequently
      overlooked, however, is the influence of other social and health determinants.
      This article highlights the importance of family and household income in
      determining the ability of children to withstand the shocks of catastrophic
      events. Children raised in lower income families are made disadvantaged in
      multiple ways; by poor living and neighbourhood conditions, less stable home
      environments, as well as lower levels of education and health care. During
      disasters, lower income families and children suffer disproportionately, both
      because they are frequently the hardest hit but also because they have fewer
      resources with which to cope. The article emphasises not only the importance of
      understanding the vulnerability of children within a broader family context, but
      a continuing requirement for public health and emergency planners to integrate
      more fully the diverse needs of children and families into emergency preparedness
      policies and plans.

PMID- 20798188
TI  - Radiation Protection Dosimetry. Preface.

PMID- 20798189
TI  - Engaging with nature to promote health: bridging research silos to examine the
      evidence.
AB  - While there is considerable research on environmental contamination and
      degradation, there is equally credible evidence on the healthful qualities of the
      environment. Being in and caring for nature can be health promoting for
      individuals, families, communities, ecosystems and the planet. In this paper, we
      use a conceptual model for nature-based health promotion and a socio-ecological
      model of health promotion to guide the scope, organization and critique of
      relevant literature on nature-based health promotion in several fields and
      generate recommendations for practice, policy and research. We conclude that
      participatory community-based research is needed to build local knowledge and
      create systemic change in practice and policy to support healthy living for
      people and the planet.

PMID- 20798190
TI  - Ultrasound accurately reflects the jugular venous examination but underestimates
      central venous pressure.
AB  - BACKGROUND: Bedside ultrasound examination could be used to assess jugular venous
      pressure (JVP), and thus central venous pressure (CVP), more reliably than
      clinical examination. METHODS: The study was a prospective, blinded evaluation
      comparing physical examination of external jugular venous pressure (JVPEXT),
      internal jugular venous pressure (JVPINT), and ultrasound collapse pressure (UCP)
      with CVP measured using an indwelling catheter. We compared the examination of
      the external and internal JVP with each other and with the UCP and CVP. JVPEXT,
      JVPINT, UCP, and CVP were compared graphically using Bland-Altman plots, and
      correlation coefficients were calculated. RESULTS: The correlation coefficients
      comparing CVP to UCP, JVPEXT, and JVPINT were 0.62, 0.57, and 0.50, respectively.
      When UCP was compared with JVPEXT and JVPINT, correlation coefficients were 0.91
      and 0.81, respectively. Last, the correlation coefficient comparing JVPEXT and
      JVPINT was 0.98. The Bland-Altman graphical comparison of methods technique
      revealed that CVP was often underestimated by UCP, and clinical examination of
      JVPEXT and JVPINT. In contrast, there was no systematic bias between UCP and
      either JVPEXT or JVPINT, nor between JVPEXT and JVPINT. CONCLUSIONS: Ultrasound
      examination is capable of measuring accurately the JVP as judged from the
      internal or external jugular vein. However, like the JVP, ultrasound typically
      underestimates CVP. A systematic bias between UCP and CVP suggests the presence
      of a variable degree of venous tone, possibly signaling contraction of jugular
      venous smooth muscle. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01099241; URL:
      clinicaltrials.gov.

PMID- 20798191
TI  - Does sunscreen prevent epidermal growth factor receptor (EGFR) inhibitor-induced
      rash? Results of a placebo-controlled trial from the North Central Cancer
      Treatment Group (N05C4).
AB  - PURPOSE: Rash occurs in >50% of patients prescribed epidermal growth factor
      receptor (EGFR) inhibitors. This study was undertaken to determine whether
      sunscreen prevents or mitigates these rashes. METHODS: This placebo-controlled,
      double-blinded trial enrolled rash-free patients starting an EGFR inhibitor.
      Patients were randomly assigned to sunscreen with a sun protection factor of 60
      applied twice a day for 28 days versus placebo. They were then monitored for rash
      and quality of life (Skindex-16) during the 4-week intervention and for an
      additional 4 weeks. RESULTS: Fifty-four patients received sunscreen, and 56
      received placebo; the arms were balanced at baseline. During the 4-week
      intervention, physician-reported rash occurred in 38 (78%) and 39 (80%) sunscreen
      treated and placebo-exposed patients, respectively (p = 1.00); no significant
      differences in rash rates emerged over the additional 4 weeks. There were no
      significant differences in rash severity, and patient-reported outcomes of rash
      yielded similar conclusions. Adjustment for sun intensity by geographical zone,
      season, and use of photosensitivity medications did not yield a significant
      difference in rash across study arms (p = .20). Quality of life scores declined
      but remained comparable between arms. CONCLUSIONS: Sunscreen, as prescribed in
      this trial, did not prevent or attenuate EGFR inhibitor-induced rash.

PMID- 20798192
TI  - A phase I study of weekly topotecan in combination with pemetrexed in patients
      with advanced malignancies.
AB  - INTRODUCTION: This phase I study evaluated the safety, tolerability, preliminary
      antitumor activity, and pharmacokinetic interaction of weekly topotecan (days 1
      and 8) in combination with pemetrexed (day 1 only) in patients with advanced
      solid tumors. METHODS: Patients received topotecan (3.0-4.0 mg/m(2) i.v. days 1
      and 8) and pemetrexed (375-500 mg/m(2) i.v. day 1) over 21-day cycles. Patients
      were accrued across five different dose levels and were observed for safety,
      tolerability, and preliminary activity. RESULTS: Twenty-six patients received 120
      cycles of pemetrexed and topotecan, including five patients who received 8, 8,
      10, 12, and 17 cycles without dose reductions, confirming a lack of cumulative
      myelosuppression. Four patients received topotecan (4.0 mg/m(2) i.v.) and
      pemetrexed (500 mg/m(2) i.v.), but experienced two dose-limiting toxicities
      (febrile neutropenia, grade 4 thrombocytopenia). As a result, the topotecan (3.5
      mg/m(2) i.v.) and pemetrexed (500 mg/m(2) i.v.) group was expanded to 12
      patients. The only grade 3 or 4 nonhematologic toxicity was one episode of grade
      3 fatigue; no grade 3 or 4 nausea/vomiting/diarrhea, mucositis, or rash was
      reported. One non-small cell lung cancer (NSCLC) patient (12 months) and one soft
      tissue sarcoma patient (6 months) achieved a partial response. CONCLUSIONS:
      Weekly topotecan plus every-3-week pemetrexed was well tolerated and active. Full
      doses of topotecan plus pemetrexed caused brief reversible myelosuppression with
      minimal dose delays/reductions; no grade 3 or 4 nausea/vomiting/diarrhea,
      mucositis, or rash was reported. All six NSCLC patients at the recommended phase
      II dose had at least stable disease as a best response, including one partial
      response lasting 12 months. There was no evidence of an effect of pemetrexed on
      topotecan pharmacokinetics. Collectively, these data suggest that further phase
      II exploration of weekly topotecan plus every-3-week pemetrexed for advanced
      malignancies is indicated.

PMID- 20798193
TI  - Cetuximab may inhibit tumor growth and angiogenesis induced by ionizing
      radiation: a preclinical rationale for maintenance treatment after radiotherapy.
AB  - BACKGROUND: The benefits of radiotherapy and cetuximab have encouraged evaluation
      of cetuximab after radiotherapy. The aims of this study were to preclinically
      evaluate the efficacy of cetuximab maintenance after radiotherapy and eventually
      determine its mechanisms of action. METHODS: The A431 human carcinoma cell line
      was treated in culture with fractionated radiotherapy and cetuximab. The
      surviving cells were injected s.c. into nude mice to mimic microscopic residual
      disease. The animals were randomized to receive either cetuximab or saline
      solution. Tumor growth, cell proliferation (Ki-67), microvessel density (MVD),
      epidermal growth factor receptor (EGFR) and transforming growth factor (TGF
      alpha) mRNA transcription, and vascular endothelial growth factor (VEGF)
      secretion were measured. RESULTS: Tumors from irradiated cells had a faster
      growth rate, higher Ki-67 index, and greater angiogenesis than tumors from
      untreated cells. This aggressive phenotype was associated with in vitro radiation
      induced extracellular signal-related kinase (ERK)-1/2 and Akt activation, greater
      EGFR and TGF-alpha transcription, and augmented VEGF secretion, all of which were
      inhibited by cetuximab. In cetuximab-treated mice with tumors arising from
      irradiated cells, time to volume was longer by a factor of 3.52, whereas the Ki
      67 index and MVD were 1.57 and 1.49 times lower, respectively, a larger
      enhancement than seen in tumors from untreated cells. These findings suggest that
      cells surviving radiation may express factors that promote cell survival and
      induce an aggressive phenotype that may potentially be blocked by cetuximab
      maintenance therapy. CONCLUSIONS: These results support the clinical evaluation
      of adjuvant therapy with cetuximab after radiotherapy in EGFR-dependent
      carcinomas.

PMID- 20798194
TI  - Epoetin alfa improves anemia and anemia-related, patient-reported outcomes in
      patients with breast cancer receiving myelotoxic chemotherapy: results of a
      European, multicenter, randomized, controlled trial.
AB  - PURPOSE: To evaluate the effects of epoetin alfa on patient-reported outcomes
      (PROs) in patients with breast cancer receiving myelotoxic chemotherapy.
      MATERIALS AND METHODS: Women with hemoglobin concentrations <= 12.0 g/dl and an
      Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0-3 were
      randomized 1:1 to receive epoetin alfa (10,000 IU 3 times weekly) or best
      standard care (BSC) during chemotherapy. The primary endpoint was the change from
      baseline in the total anemia subscale assessed by the Functional Assessment of
      Cancer Therapy-Anemia (FACT-An) questionnaire after 12 weeks of treatment. The
      fatigue and nonfatigue subscales from the FACT-An, the Cancer Linear Analog Scale
      (CLAS), hemoglobin changes, ECOG PS score, tumor response, overall survival, and
      safety also were evaluated. RESULTS: Of 223 patients randomized, 216 constituted
      the modified intent-to-treat population. Percentage changes in the total anemia
      subscale of the FACT-An were significantly different between epoetin alfa
      treatment (14.2%) and BSC (-0.5%; p = .002), favoring epoetin alfa; so were
      changes in the FACT-An fatigue subscale (epoetin alfa, 17.5%; BSC, -0.9%; p =
      .003) and nonfatigue subscale (epoetin alfa, 8.8%; BSC, 0.2%; p = .008). Similar
      results were observed with the CLAS. Hemoglobin concentrations > 12 g/dl were
      more common with epoetin alfa (62.0%) than with BSC (27.6%). Tumor response, ECOG
      PS score, 12-month survival rate, and the incidence of serious treatment-emergent
      adverse events were similar between groups. CONCLUSION: Early intervention with
      epoetin alfa was well tolerated and improved anemia-related PROs in patients with
      breast cancer receiving myelotoxic chemotherapy.

PMID- 20798195
TI  - Therapeutic cancer vaccines in prostate cancer: the paradox of improved survival
      without changes in time to progression.
AB  - Therapeutic cancer vaccines represent a new class of agents in the treatment of
      cancer. Sipuleucel-T is an antigen-presenting cell-based vaccine that recently
      demonstrated a significant 4.8-month improvement in overall survival in advanced
      prostate cancer patients and was well tolerated. The findings of that study have
      been met with skepticism, primarily because the agent did not change initial
      disease progression and yet led to longer survival. Although the commonly
      accepted treatment paradigm suggests that treatments should initially decrease
      tumor volume, perhaps vaccines work differently. Vaccines may induce delayed
      responses not seen in the first few months of therapy or they may initiate a
      dynamic immune response that ultimately slows the tumor growth rate, resulting in
      longer survival. Subsequent therapies may also combine with the induced immune
      response, resulting in a combination that is more effective than conventional
      treatments alone. Also, other treatments may alter tumor-associated antigen
      expression, enhancing the immune response. Future trials are currently planned to
      investigate these hypotheses; however, the results of the sipuleucel-T vaccine in
      prostate cancer should not be dismissed. Results with another vaccine in prostate
      cancer are similar, perhaps suggesting a class effect. In a broader context,
      clinicians may need to reconsider how they measure success. Several agents have
      been approved that produce superior disease progression results, but do not
      affect overall survival. Given the toxicity and costs of cancer therapies,
      perhaps studies should put more weight on long-term survival endpoints than on
      short-term endpoints that may be less consequential.

PMID- 20798196
TI  - Quality of life in hormone receptor-positive HER-2+ metastatic breast cancer
      patients during treatment with letrozole alone or in combination with lapatinib.
AB  - BACKGROUND: A phase III trial compared lapatinib plus letrozole (L + Let) with
      letrozole plus placebo (Let) as first-line therapy for hormone receptor (HR)(+)
      metastatic breast cancer (MBC) patients. The primary endpoint of progression-free
      survival (PFS) in patients whose tumors were human epidermal growth factor
      receptor (HER)-2(+) was significantly longer for L + Let than for Let (8.2 months
      versus 3 months; p = .019). This analysis focuses on quality of life (QOL) in the
      HER-2(+) population. METHODS: QOL was assessed at screening, every 12 weeks, and
      at withdrawal using the Functional Assessment of Cancer Therapy-Breast (FACT-B).
      Changes from baseline were analyzed and the proportions of patients achieving
      minimally important differences in QOL scores were compared. Additional
      exploratory analyses evaluated how QOL changes reflected tumor progression
      status. RESULTS: Among the 1,286 patients randomized, 219 had HER-2(+) tumors.
      Baseline QOL scores were comparable in the two arms. Mean changes in QOL scores
      were generally stable over time for patients who stayed on study. The average
      change from baseline on the FACT-B total score in both arms was positive at all
      scheduled visits through week 48. There was no significant difference between the
      two treatment arms in the percentage of QOL responders. CONCLUSION: The addition
      of lapatinib to letrozole led to a significantly longer PFS interval while
      maintaining QOL during treatment, when compared with letrozole alone, thus
      confirming the clinical benefit of the combination therapy in the HR(+) HER-2(+)
      MBC patient population. This all oral regimen provides an effective option in
      this patient population, delaying the need for chemotherapy and its accompanying
      side effects.

PMID- 20798197
TI  - Survival trends in head and neck cancer: opportunities for improving outcomes.

PMID- 20798198
TI  - Changes in survival in head and neck cancers in the late 20th and early 21st
      century: a period analysis.
AB  - BACKGROUND: Therapy for head and neck cancers has evolved over the past decade,
      but few detailed analyses of recent developments in survival on the population
      level have been published. METHODS: We use period analysis and modeled period
      analysis to disclose recent trends in survival in patients with head and neck
      cancer. Data are derived from the Surveillance, Epidemiology, and End Results
      limited-use database. RESULTS: A major, statistically significant improvement in
      survival was observed, with the overall 5-year relative survival rate going from
      54.7% in 1992-1996 to 65.9% in 2002-2006. Subgroup analysis showed improvement in
      cancers of the oral cavity, tongue, tonsils, and nasopharynx, with the greatest
      improvements observed in tonsillar carcinoma (+22.2 percentage points) and
      carcinoma of the tongue (+14.4 percentage points). Further analysis of survival
      for oral cavity, tonsillar, and tongue carcinoma revealed improvements in
      survival at each stage and across all age groups except for patients aged >= 75
      years, with the greatest improvement occurring in locally advanced disease and in
      patients aged 55-64 years for carcinoma of the tongue and tonsils and those aged
      15-44 years for oral cavity cancers. CONCLUSIONS: Survival has substantially
      improved for head and neck cancer patients over the past decade. The greatest
      improvement was seen in tonsillar and tongue cancers.

PMID- 20798199
TI  - Rapamycin and thalidomide treatment of a patient with refractory metastatic
      gastroesophageal adenocarcinoma: a case report.

PMID- 20798200
TI  - Poor sleep quality and fatigue but no excessive daytime sleepiness in myotonic
      dystrophy type 2.
AB  - BACKGROUND: In myotonic dystrophy type 1 (DM1), sleep disorders are common, with
      excessive daytime sleepiness (EDS) as a predominant feature. In myotonic
      dystrophy type 2 (DM2), the presence of sleep disturbances is unknown. OBJECTIVE:
      To investigate the frequency of EDS, poor sleep quality and fatigue in DM2.
      METHODS: 29 genetically proven DM2 patients were surveyed using the Epworth
      Sleepiness Scale, Pittsburgh Sleep Quality Index (PSQI) and Checklist Individual
      Strength. The results were compared with 29 adult onset DM1 patients and 65
      population controls, both matched for age and sex. RESULTS: Only 6.9% of DM2
      patients had EDS compared with 44.8% of DM1 patients and 6.2% of population
      controls (DM2-DM1: p=0.001; DM2-controls: p=0.51). Sleep quality was poor (PSQI
      >5) in both DM2 and DM1 groups, and differed significantly from population
      controls (DM2 6.5+/-3.0; DM1 6.2+/-3.7; controls 4.3+/-3.0; DM2-controls:
      p=0.002). Poor sleep quality was not explained by depression or other comorbidity
      but was mainly due to sleep disturbances as a result of nocturnal pain.
      Comparable with the DM1 group, DM2 patients experienced severe fatigue (DM2
      38.7+/-13.1; DM1 42.9+/-8.5; controls 21.1+/-11.1; DM2-controls: p<0.001).
      Results were not confounded by abnormal thyroid function or medication use.
      CONCLUSION: These results provide new insight into the phenotype of DM2 and have
      consequences for clinical treatment. In addition, the absence of EDS in DM2 is a
      new discriminative feature with adult onset DM1.

PMID- 20798201
TI  - New cases of adult-onset Sandhoff disease with a cerebellar or lower motor neuron
      phenotype.
AB  - Sandhoff disease is a lipid-storage disorder caused by a defect in ganglioside
      metabolism. It is caused by a lack of functional N-acetyl-beta-d-glucosaminidase
      A and B due to mutations in the HEXB gene. Typical, early-onset Sandhoff disease
      presents before 9 months of age with progressive psychomotor retardation and
      early death. A late-onset form of Sandhoff disease is rare, and its symptoms are
      heterogeneous. As drug trials that aim to intervene in the disease mechanism are
      emerging, the recognition and identification of Sandhoff disease patients
      particularly those with atypical phenotypes-are becoming more important. The
      authors describe six new late-onset Sandhoff cases demonstrating cerebellar
      ataxia or lower motor neuron (LMN) involvement combined with, mostly subclinical,
      neuropathy. Two different mutations were found: IVS 12-26 G/A and c.1514G-->A. In
      patients with either progressive cerebellar ataxia or LMN disease in the setting
      of a possibly recessive disorder, Sandhoff disease should be suspected, even when
      the onset age is over 45 years.

PMID- 20798203
TI  - Behavioural symptoms in progressive supranuclear palsy and frontotemporal
      dementia.

PMID- 20798204
TI  - Exposure to breast milk in infancy and risk of adult breast cancer: more
      scientific data are needed.

PMID- 20798205
TI  - Citizens' juries: more questions than answers?

PMID- 20798206
TI  - Physical activity promotion: a natural selection?

PMID- 20798207
TI  - Screening for oral premalignancy and cancer: what platform and which biomarkers?
AB  - This perspective on the report by Pattani et al. in this issue of the journal
      (beginning on page 1093) examines the utility of detecting hypermethylation of
      the candidate tumor suppressor genes endothelin receptor type B (EDNRB) and
      kinesin family member 1A (KIF1A) as a means of oral cancer or premalignancy
      screening. The data discussed here raise the possibility that saliva-based
      hypermethylation studies may hold promise as a cancer screening platform. This
      perspective also discusses some of the challenges and current limitations of
      developing biomarkers to screen not only for oral premalignancy and early cancer
      but for human papillomavirus-related oropharyngeal neoplasia as well.

PMID- 20798209
TI  - Assessment of dental anomalies on panoramic radiographs: inter- and intraexaminer
      agreement.
AB  - The presence of dental anomalies has been rated radiographically in a number of
      studies. However, since the reliability of the assessment of these anomalies has
      rarely been investigated, the aim of this study was to examine inter- and
      intraexaminer agreement in identifying morphological dental anomalies, such as
      tooth agenesis, dilacerated, pipette-shaped, blunt, pointed, and short roots. Pre
      treatment panoramic radiographs of 40 patients (13 males and 27 females; mean age
      27.7 +/- 10.8 years) treated between 1983 and 2008 were selected. Four examiners
      independently assessed the radiographs twice. For a dilacerated root and
      agenesis, a definition was given. For pipette-shaped, blunt, or pointed roots, a
      drawing was shown, and for a short root, a ratio was used to identify the
      anomaly. Intraexaminer agreement of the assessments of the dental anomalies was
      presented by Cohen's Kappa and varied between -0.01 for short roots and 1.00 for
      agenesis. With respect to short roots, three of the examiners did not rate them
      to be present on at least one measurement occasion. This implies that
      intraexaminer agreement could not be calculated for these three examiners.
      Interexaminer agreement for dilacerated roots varied between 0.14 and 0.50, for
      pipette-shaped roots between -0.01 and 0.33, for blunt roots between 0.05 and
      0.32, and for pointed roots between 0.17 and 0.37. All values for agenesis were
      1.00. It can be concluded that assessing agenesis on panoramic radiographs is
      reliable. Rating the presence of dilacerated, pipette-shaped, blunt, pointed, and
      short roots on panoramic radiographs, however, does not result in a reliable
      assessment.

PMID- 20798210
TI  - Rapid maxillary expansion screws on the test bench--a pilot study.
AB  - In order to apply high, short-term forces during rapid maxillary expansion (RME)
      to the sutures of the maxilla with minimum loss of force and without causing
      unwanted side-effects (dentoalveolar tipping, etc.), the appliance should be as
      rigid as possible. The retention arms of the RME screws, representing a
      particularly vulnerable and stressed weak point of RME appliances, were the focus
      of this laboratory technical study. Retention arms of 16 types of RME screws
      comprising four arms and one with eight arms were examined using a three-point
      bending test. According to their ability to absorb the applied bending loads, the
      screws were classified in product groups from 1 (highest) to 6 (lowest). Fifteen
      of the tested retention arms (stainless steel), despite having the same diameter
      (1.48-1.49 mm), differed up to 69.81 per cent between the highest (288.0 N) and
      lowest (169.6 N) maximum force parameters and up to 66.40 per cent between the
      highest (3325.9 N/mm(2)) and lowest (1998.7 N/mm(2)) maximum bending stress
      parameters. Due to optimum formability, though reduced rigidity, a titanium screw
      for nickel-sensitive patients (group 6) displayed the lowest force and bending
      tension values. The stainless steel double arms of the eight-arm screw device
      welded on both ends displayed the highest force data. The mean ductilities of the
      groups with the most and least rigid single steel arms differed by 22.77 per
      cent. Statistical analysis using the Pearson correlation coefficient revealed a
      significant indirect correlation between ductility and both maximum force (r = 
      0.780, P < 0.001) and maximum bending stress (r = -0.778, P < 0.001). The
      SUPERscrews, the Tiger Dental four-arm screw (group 1), and the eight-arm screw
      displayed the highest capacity to absorb an applied bending load. The screws in
      groups 3-6 appear acceptable for RME during the pre-pubertal period, whereas in
      the pubertal and post-pubertal period, groups 1 and 2 are sufficient. In early
      adulthood only the screws in group 1 and especially the eight-arm screw seem
      advisable, as mechanical demands increase with age.

PMID- 20798208
TI  - Endothelin receptor type B gene promoter hypermethylation in salivary rinses is
      independently associated with risk of oral cavity cancer and premalignancy.
AB  - Endothelin receptor type B (EDNRB) and kinesin family member 1A (KIF1A) are
      candidate tumor suppressor genes that are inactivated in cancers. In this study,
      we evaluated the promoter hypermethylation of EDNRB and KIF1A and their potential
      use for risk classification in prospectively collected salivary rinses from
      patients with premalignant/malignant oral cavity lesions. Quantitative
      methylation-specific PCR was performed to analyze the methylation status of EDNRB
      and KIF1A in salivary rinses of 191 patients. We proceeded to determine the
      association of methylation status with histologic diagnosis and estimate
      classification accuracy. On univariate analysis, diagnosis of dysplasia/cancer
      was associated with age and KIF1A or EDNRB methylation. Methylation of EDNRB
      highly correlated with that of KIF1A (P < 0.0001). On multivariable modeling,
      histologic diagnosis was independently associated with EDNRB (P = 0.0003) or
      KIF1A (P = 0.027) methylation. A subset of patients analyzed (n = 161) without
      prior biopsy-proven malignancy received clinical risk classification based on
      examination. On univariate analysis, EDNRB and risk classification were
      associated with diagnosis of dysplasia/cancer and remained significant on
      multivariate analysis (EDNRB: P = 0.047, risk classification: P = 0.008).
      Clinical risk classification identified dysplasia/cancer with a sensitivity of
      71% and a specificity of 58%. The sensitivity of clinical risk classification
      combined with EDNRB methylation improved to 75%. EDNRB methylation in salivary
      rinses was independently associated with histologic diagnosis of premalignancy
      and malignancy and may have potential in classifying patients at risk for oral
      premalignant and malignant lesions in settings without access to a skilled dental
      practitioner. This may also potentially identify patients with premalignant and
      malignant lesions that do not meet the criteria for high clinical risk based on
      skilled dental examination.

PMID- 20798211
TI  - Stress change on the temporomandibular joint in mandibular prognathism subjects
      with asymmetry after orthognathic surgery.
AB  - The purpose of this study was to evaluate changes in stress on the
      temporomandibular joint (TMJ) in 80 Japanese subjects (21 males and 59 females,
      mean age 23.7 years) with mandibular prognathism, with and without asymmetry
      after orthognathic surgery using the rigid bodies spring model (RBSM). The
      asymmetric group consisted of 40 subjects whose Mx-Md midline was more than 3
      degrees. The remaining 40 subjects formed the symmetric group. The geometry of
      the stress analysis model was based on frontal cephalograms of the subjects.
      Menton (Me), the centre point of occlusal force on a line connecting the
      bilateral buccal cusps of the second molars, and the most lateral, superior, and
      medial points on the condyle were plotted on a computer display and stress on the
      condyle was calculated with the two-dimensional RBSM program, Fortran. The degree
      (force partition) of the resultant force, the direction (angulation), and the
      displacement (X, Y) of each condyle were calculated and the horizontal
      displacement (u), the vertical displacement (v), and rotation displacement
      (theta) of the mandibular body at Me were calculated pre- and post-operatively.
      The data was analysed using paired and unpaired t-tests. For the vertical (v) and
      rotational (theta) displacement, the post-operative value was smaller than the
      pre-operative value (v: P < 0.001, theta: P = 0.0063) in the asymmetric group.
      For angulation and the X-component, the post-operative value was smaller than
      that pre-operatively on the deviated (angulation: P = 0.0074, X-component: P =
      0.0003) and non-deviated (angulation: P = 0.0024, X-component: P = 0.001) side in
      the asymmetric group. However, there was no significant difference between the
      pre- and post-operative value for any parameter in the symmetric group. These
      findings suggest that surgical correction of mandibular prognathism, with and
      without asymmetry, could induce an improvement in stress balance on the TMJ in
      the frontal aspect.

PMID- 20798212
TI  - Electromyographic evaluation of masticatory, neck, and trunk muscle activity in
      patients with posterior crossbites.
AB  - This study investigated the pattern of masticatory, neck, and trunk muscle
      activity in patients with posterior crossbites and associated mandibular
      displacement. The test group consisted of 75 patients [45 males mean age 19.5
      years, SD 5.6 years, and 30 females mean age 20.4 (SD 3.2) years]. Of this group,
      25 patients presented a left posterior crossbite, 25 a right posterior crossbite,
      and the remaining 25 patients a bilateral posterior crossbite. A control group of
      25 subjects (19 males and 6 females aged 22.5 +/- 5.8 years) without any
      crossbite were included. Surface electromyographic (sEMG) activity was recorded
      bilaterally, in the mandibular rest position and during maximum voluntary
      clenching (MVC), at the following sites: anterior and posterior temporal,
      masseter, sternocleidomastoid (SCM), upper and lower trapezius, and cervical
      muscles. In the mandibular rest position, patients with unilateral crossbites
      showed a significant difference (P < 0.05) in sEMG activity of the anterior
      temporal muscle, with the greatest activity being detected on the side to which
      the mandible displaced. Control subjects demonstrated significantly lower (P <
      0.05) sEMG activity but only in the SCM muscle when compared with patients with
      bilateral posterior crossbites; no such differences were detected in relation to
      unilateral crossbites. During MVC, control subjects showed significantly lower (P
      < 0.01) sEMG activity in both the SCM and the posterior cervical muscles compared
      with patients demonstrating both unilateral and bilateral crossbites. The
      findings of the present study indicate that the presence of a crossbite can
      affect electromyography activity of masticatory, neck, and trunk muscles.

PMID- 20798213
TI  - Diagnostic and therapeutic approach in a rare case of primary bilateral adrenal
      tuberculosis.
AB  - Here, we report a case of a febrile patient with primary bilateral adrenalitis
      who was successfully treated with an antituberculous regimen. Primary isolated
      tubercular adrenalitis is a very rare clinical entity but it should be considered
      in cases of fever and enlargement of the adrenal glands. Integration of
      radiological pattern data with epidemiological, clinical and immunological data
      has high accuracy and specificity, even without histological examination.

PMID- 20798214
TI  - Purified galactooligosaccharide, derived from a mixture produced by the enzymic
      activity of Bifidobacterium bifidum, reduces Salmonella enterica serovar
      Typhimurium adhesion and invasion in vitro and in vivo.
AB  - The prebiotic Bimuno((r)) is a mixture containing galactooligosaccharides (GOSs),
      produced by the galactosyltransferase activity of Bifidobacterium bifidum NCIMB
      41171 using lactose as the substrate. Previous in vivo and in vitro studies
      demonstrating the efficacy of Bimuno((r)) in reducing Salmonella enterica serovar
      Typhimurium (S. Typhimurium) colonization did not ascertain whether or not the
      protective effects could be attributed to the prebiotic component GOS. Here we
      wished to test the hypothesis that GOS, derived from Bimuno((r)), may confer the
      direct anti-invasive and protective effects of Bimuno((r)). In this study the
      efficacy of Bimuno((r)), a basal solution of Bimuno((r)) without GOS [which
      contained glucose, galactose, lactose, maltodextrin and gum arabic in the same
      relative proportions (w/w) as they are found in Bimuno((r))] and purified GOS to
      reduce S. Typhimurium adhesion and invasion was assessed using a series of in
      vitro and in vivo models. The novel use of three dimensionally cultured HT-29-16E
      cells to study prebiotics in vitro demonstrated that the presence of ~ 5 mg
      Bimuno((r)) ml(-1) or ~ 2.5 mg GOS ml(-1) significantly reduced the invasion of
      S. Typhimurium (SL1344nal(r)) (P<0.0001). Furthermore, ~ 2.5 mg GOS ml(-1)
      significantly reduced the adherence of S. Typhimurium (SL1344nal(r)) (P<0.0001).
      It was demonstrated that cells produced using this system formed multi-layered
      aggregates of cells that displayed excellent formation of brush borders and tight
      junctions. In the murine ligated ileal gut loops, the presence of Bimuno((r)) or
      GOS prevented the adherence or invasion of S. Typhimurium to enterocytes, and
      thus reduced its associated pathology. This protection appeared to correlate with
      significant reductions in the neutral and acidic mucins detected in goblet cells,
      possibly as a consequence of stimulating the cells to secrete the mucin into the
      lumen. In all assays, Bimuno((r)) without GOS conferred no such protection,
      indicating that the basal solution confers no protective effects against S.
      Typhimurium. Collectively, the studies presented here clearly indicate that the
      protective effects conferred by Bimuno((r)) can be attributed to GOS.

PMID- 20798215
TI  - A fatal Vibrio cholerae O37 enteritis.

PMID- 20798216
TI  - Influence of particle size on the pathology and efficacy of vaccination in a
      murine model of inhalational anthrax.
AB  - Deposition of Bacillus anthracis endospores within either the lungs or nasal
      passages of A/J mice after aerosol exposure was influenced by different particle
      sized aerosols and resulted in different infection kinetics. The infection
      resulting from the inhalation of endospores within a 12 MUm particle aerosol was
      prolonged compared to that from a 1 MUm particle aerosol with a mean time-to
      death of 161 +/- 16.1 h and 101.6 +/- 10.4 h, respectively. Inhalation of
      endospores within 1 MUm or 12 MUm particle aerosols resulted in a median lethal
      dose of 2432 and 7656 c.f.u., respectively. Initial involvement of the upper
      respiratory tract lymph nodes was observed in 75-83% of mice exposed to either
      the 1 MUm or 12 MUm particle inhalational infections. Lung deposition was
      significantly greater after inhalation of the 1 MUm particle aerosol with
      pronounced involvement of the mediastinal lymph node. Gastrointestinal
      involvement was observed only in mice exposed to 12 MUm particle aerosols where
      bacteriological and histopathological analysis indicated primary gastritis (17%),
      activation of the Peyer's patches (72%) and colonization and necrosis of the
      mesenteric lymph nodes (67%). Terminal disease was characterized by bacteraemia
      in both inhalational infections with preferential dissemination to spleen, liver,
      kidneys and thymus. Immunization with 1 MUg recombinant protective antigen
      vaccine was equally efficacious against B. anthracis infections arising from the
      inhalation of 1 and 12 MUm particle aerosols, providing 73-80% survival under a
      suboptimum immunization schedule.

PMID- 20798217
TI  - Synergistic chemosensitivity of triple-negative breast cancer cell lines to
      poly(ADP-Ribose) polymerase inhibition, gemcitabine, and cisplatin.
AB  - The basal-like subtype of breast cancer is characterized by a triple-negative
      (TN) phenotype (estrogen receptor, progesterone receptor, and human epidermal
      growth factor receptor-2/neu negative). TN breast cancers share similar gene
      expression profiles and DNA repair deficiencies with BRCA1-associated breast
      cancers. BRCA1-mutant cells exhibit sensitivity to gemcitabine, cisplatin, and
      poly(ADP-ribose) polymerase (PARP) inhibition; therefore, we hypothesized that TN
      cancer cells may also exhibit sensitivity to these drugs. In this study, we
      report that TN breast cancer cells are more sensitive to these drugs compared
      with non-TN breast cancer cells. Moreover, combination treatments indicated that
      PARP inhibition by the small-molecule inhibitor PJ34 or siRNA knockdown
      synergized with gemcitabine and cisplatin in TN cells but not in luminal cancer
      cells. TN cells exhibited reduced repair of UV-induced cyclobutane pyrimidine
      dimers after PARP inhibition, suggesting that the synergistic effect of PJ34 and
      gemcitabine or cisplatin reflected inefficient nucleotide excision repair.
      Mechanistic investigations revealed that in TN cells, PJ34 reduced the levels of
      DeltaNp63alpha with a concurrent increase in p73 and its downstream target p21.
      Thus, the sensitivity to combination treatment seemed to be mediated by sustained
      DNA damage and inefficient DNA repair triggering p63/p73-mediated apoptosis. Our
      results suggest a novel therapeutic strategy to treat women with TN breast
      cancer, an aggressive disease that presently lacks effective treatment options.

PMID- 20798218
TI  - Dietary fish oil alters T lymphocyte cell populations and exacerbates disease in
      a mouse model of inflammatory colitis.
AB  - Inflammatory bowel diseases (IBD) increase the risk of developing colorectal
      cancer. Dietary components that reduce inflammation are associated with lower
      cancer risk. The long-chain omega-3 fatty acid docosahexaenoic acid (DHA) is
      present in fish oil and has potent anti-inflammatory properties. The objective of
      this study is to determine whether dietary fish oil enriched with DHA (DFO) could
      reduce experimentally induced colitis and colon cancer risk in a mouse model.
      When SMAD3-/- mice are exposed to Helicobacter hepaticus, mild colitis is
      observed 4 weeks postinfection. Mice were fed isocaloric diets modified to
      include corn oil, safflower oil, or DFO (doses ranging from 0.75% to 6.00%) as
      the fatty acid source for 8 weeks. Mice were gavaged with H. hepaticus; DFO
      feeding was continued; and mice were sacrificed 4 weeks after infection. The
      colon and cecum were collected for histopathology. Spleens and mesenteric lymph
      nodes were collected and analyzed for T-cell populations using flow cytometry.
      Contrary to expectations, DFO induced severe colitis and adenocarcinoma
      formation. DFO consumption was associated with decreased CD8(+) cell frequency
      and diminished CD69 expression on CD4(+) and CD8(+) T-cell populations. Mice
      consuming DFO also exhibited higher FoxP3(+) CD25(+) CD4(+) T regulatory cell
      frequency, FoxP3 expression, and altered L-selectin expression during infection.
      We concluded that DFO-fed mice may be less equipped to mount a successful
      response to H. hepaticus infection, increasing colon cancer risk. These results
      support the need to establish a tolerable upper limit for DHA intake particularly
      in the context of chronic inflammatory conditions such as IBD.

PMID- 20798219
TI  - Luteogenesis during the estrous cycle in Asian elephants (Elephas maximus).
AB  - The occurrence of multiple corpora lutea (CLs) in the ovaries of the cycling and
      pregnant elephant, a monovulatory mammal, has driven scientific discussions
      during the past five decades. However, fundamental knowledge on luteogenesis is
      lacking. In this long-term study, CL formation and regression throughout the
      estrous cycle were monitored using transrectal 2D- and 3D ultrasonography in 33
      captive Asian elephants. Serum or urinary progestagens (P(m)) were measured to
      determine the reproductive cycle stage. In seven females, serum P(m) and LH
      concentrations were directly related to ovarian events. We have found two
      different modalities of luteal development: one for the accessory CL (acCL) and
      one for the ovulatory CL (ovCL). acCLs were derived from luteinization of larger,
      subordinate follicles after the first anovulatory LH peak. The dominant follicle
      produced the largest CL after the second (ovulatory) LH peak. The first luteal
      tissue formation became visible ~ 10 days after the respective LH peak. After
      ovulation, it took 29.8 +/- 5.0 days for the acCLs to reach their maximum
      diameter, whereas the ovCL reached a significantly larger size (33.2 +/- 2.3 mm,
      P<0.0001) about 10-15 days later. All CLs were visible throughout the new
      follicular phase, with some of the larger ones still present in the subsequent
      luteal period. In this study, we have demonstrated that Asian elephants have
      evolved a novel method for luteal development and function, and by repeatedly
      forming two types of distinctly different CLs for every reproductive cycle, they
      have ensured that there will be sufficient luteal capacity for maintaining a 22
      month pregnancy should conception occur.

PMID- 20798220
TI  - NICE recommends greater use of sunscreens at school and work to prevent skin
      cancer.

PMID- 20798221
TI  - Cancer doctors pledge to widen access to pain relief in developing countries.

PMID- 20798222
TI  - Fertility regulator seeks views on donation compensation.

PMID- 20798223
TI  - Judge halts US funding of embryonic stem cell research.

PMID- 20798224
TI  - Introduction of laparoscopic bariatric surgery in England: observational
      population cohort study.
AB  - OBJECTIVES: To describe national trends in bariatric surgery and examine the
      factors influencing outcome in bariatric surgery in England. DESIGN:
      Observational population cohort study. SETTING: Hospital Episode Statistics
      database. PARTICIPANTS: All patients who had primary gastric bypass, gastric
      banding, or sleeve gastrectomy procedures between April 2000 and March 2008. MAIN
      OUTCOME MEASURES: 30 day mortality, mortality at one year after surgery,
      unplanned readmission to hospitalwithin 28 days, and duration of stay in
      hospital. RESULTS: 6953 primary bariatric procedures were carried out during the
      study period, of which 3649 were gastric band procedures, 3191 were gastric
      bypass procedures, and 113 were sleeve gastrectomy procedures. A marked increase
      occurred in the numbers of bariatric procedures done, from 238 in 2000 to 2543 in
      2007, with an increase in the percentage of laparoscopic procedures over the
      study period (28% (66/238) laparoscopic procedures in 2000 compared with 74.5%
      (1894/2543) in 2007). Overall, 0.3% (19/6953) patients died within 30 days of
      surgery. The median length of stay in hospital was 3 (interquartile range 2-6)
      days. An unplanned readmission to hospital within 28 days of surgery occurred in
      8% (556/6953) of procedures. No significant increase in mortality or unplanned
      readmission was seen over the study period, despite the exponential increase in
      minimal access surgery and consequently bariatric surgery. CONCLUSIONS: Bariatric
      surgery has increased exponentially in England. Although postoperative weight
      loss and reoperation rates were not evaluated in this observational population
      cohort study, patients selected for gastric banding had lower postoperative
      mortality and readmission rates and a shorter length of stay than did those
      selected for gastric bypass.

PMID- 20798227
TI  - Associations between cardiovascular risk, insulin resistance, beta-cell function
      and thyroid dysfunction: a cross-sectional study in She ethnic minority group of
      Fujian Province in China.
AB  - OBJECTIVE: To investigate the associations between cardiovascular risk, insulin
      resistance (IR), beta-cell function and thyroid dysfunction in She ethnic
      minority group in China. METHODS: We enrolled 5080 participants of She ethnicity
      in this analysis eventually. We measured serum TSH and thyroid peroxidase
      antibody (TPOAb) concentrations, blood glucose and insulin levels in both fasting
      and 2-h postprandial states, serum lipid levels, blood pressure (BP), brachial
      ankle pulse wave velocity (baPWV), electrophysiological parameters, including
      T(peak)-T(end) interval (T(p-e)), QT interval and height of the R wave in lead
      aVL (RaVL), and anthropometric parameters. RESULTS: The total prevalence of
      thyroid dysfunction in this population is 12.1%. Hyperthyroid subjects had
      shorter T(p-e) interval and QT interval in electrocardiogram (ECG), while
      hypothyroid subjects had shorter T(p-e) interval and longer QT interval in ECG
      than euthyroid subjects. Neither hyperthyroid nor hypothyroid subjects showed
      significant difference in BP, pulse pressure, and baPWV compared with euthyroid
      subjects. RaVL was slightly higher in hyperthyroid subjects, though the
      difference did not reach statistical significance (P=0.08). Subjects with TSH<0.3
      mIU/l had higher blood glucose, insulin, homeostasis model assessment of insulin
      resistance (HOMA-IR), and beta-cell function (HOMA-beta), whereas subjects with
      TSH>10 mIU/l had lower insulin, HOMA-IR, and HOMA-beta than the reference group.
      There was a significant negative correlation, albeit weak, between TSH and HOMA
      IR, HOMA-beta after adjustment for confounding factors. CONCLUSIONS: Hypothyroid
      subjects may carry higher cardiovascular risk than euthyroid subjects. Moreover,
      IR and beta-cell function are inversely correlated with TSH, which may be
      explained by the decreasing insulin-antagonistic effects of thyroid hormones
      along with increasing TSH.

PMID- 20798226
TI  - Obesity-related cardiovascular risk factors after weight loss: a clinical trial
      comparing gastric bypass surgery and intensive lifestyle intervention.
AB  - OBJECTIVE: Weight reduction improves several obesity-related health conditions.
      We aimed to compare the effect of bariatric surgery and comprehensive lifestyle
      intervention on type 2 diabetes and obesity-related cardiovascular risk factors.
      DESIGN: One-year controlled clinical trial (ClinicalTrials.gov identifier
      NCT00273104). METHODS: Morbidly obese subjects (19-66 years, mean (s.d.) body
      mass index 45.1 kg/m(2) (5.6), 103 women) were treated with either Roux-en-Y
      gastric bypass surgery (n=80) or intensive lifestyle intervention at a
      rehabilitation centre (n=66). The dropout rate within both groups was 5%.
      RESULTS: Among the 76 completers in the surgery group and the 63 completers in
      the lifestyle group, mean (s.d.) 1-year weight loss was 30% (8) and 8% (9)
      respectively. Beneficial effects on glucose metabolism, blood pressure, lipids
      and low-grade inflammation were observed in both groups. Remission rates of type
      2 diabetes and hypertension were significantly higher in the surgery group than
      the lifestyle intervention group; 70 vs 33%, P=0.027, and 49 vs 23%, P=0.016. The
      improvements in glycaemic control and blood pressure were mediated by weight
      reduction. The surgery group experienced a significantly greater reduction in the
      prevalence of metabolic syndrome, albuminuria and electrocardiographic left
      ventricular hypertrophy than the lifestyle group. Gastrointestinal symptoms and
      symptomatic postprandial hypoglycaemia developed more frequently after gastric
      bypass surgery than after lifestyle intervention. There were no deaths.
      CONCLUSIONS: Type 2 diabetes and obesity-related cardiovascular risk factors were
      improved after both treatment strategies. However, the improvements were greatest
      in those patients treated with gastric bypass surgery.

PMID- 20798228
TI  - A combination of serum markers for the early detection of colorectal cancer.
AB  - PURPOSE: Fecal occult blood testing is recommended as first-line screening to
      detect colorectal cancer (CRC). We evaluated markers and marker combinations in
      serum as an alternative to improve the detection of CRC. EXPERIMENTAL DESIGN:
      Using penalized logistic regression, 6 markers were selected for evaluation in
      1,027 samples (301 CRC patients, 143 patients with adenoma, 266 controls, 141
      disease controls, and 176 patients with other cancer). The diagnostic performance
      of each marker and of marker combinations was assessed. RESULTS: To detect CRC
      from serum samples, we tested 22 biomarkers. Six markers were selected for a
      marker combination, including the known tumor markers CEA (carcinoembryonic
      antigen) and CYFRA 21-1 as well as novel markers or markers that are less
      routinely used for the detection of CRC: ferritin, osteopontin (OPN), anti-p53,
      and seprase. CEA showed the best sensitivity at 95% specificity with 43.9%,
      followed by seprase (42.4%), CYFRA 21-1 (35.5%), OPN (30.2%), ferritin (23.9%),
      and anti-p53 (20.0%). A combination of these markers gave 69.6% sensitivity at
      95% specificity and 58.7% at 98% specificity. Focusing on International Union
      against Cancer (UICC) stages 0-III reduced the sensitivity slightly to 68.0% and
      53.3%, respectively. In a subcollective, with matched stool samples (75 CRC cases
      and 234 controls), the sensitivity of the marker combination was comparable with
      fecal immunochemical testing (FIT) with 82.4% and 68.9% versus 81.8% and 72.7% at
      95% and 98% specificity, respectively. CONCLUSIONS: The performance of the serum
      marker combination is comparable with FIT. This provides a novel tool for CRC
      screening to trigger a follow-up colonoscopy for a final diagnosis.

PMID- 20798229
TI  - Mitochondrial-mediated apoptosis in lymphoma cells by the diterpenoid lactone
      andrographolide, the active component of Andrographis paniculata.
AB  - PURPOSE: Andrographolide is a diterpenoid lactone isolated from Andrographis
      paniculata (King of Bitters), an herbal medicine used in Asia. It has been
      reported to have anti-inflammatory, antihypertensive, antiviral, and immune
      stimulant properties. Furthermore, it has been shown to inhibit cancer cell
      proliferation and induce apoptosis in leukemia and solid tumor cell lines.
      EXPERIMENTAL DESIGN: We studied the Burkitt p53-mutated Ramos cell line, the
      mantle cell lymphoma (MCL) line Granta, the follicular lymphoma (FL) cell line HF
      1, and the diffuse large B-cell lymphoma (DLBCL) cell line SUDHL4, as well as
      primary cells from patients with FL, DLBCL, and MCL. RESULTS: We found that
      andrographolide resulted in dose- and time-dependent cell death as measured by
      MTT. Andrographolide significantly increased reactive oxygen species (ROS)
      production in all cell lines. To determine mechanism of cell death, we measured
      apoptosis by Annexin V/propidium iodide in the presence and absence of the
      antioxidant N-acetyl-l-cysteine (NAC), the glutathione (GSH)-depleting agent
      buthionine sulfoxamine (BSO), or caspase inhibitors. We found that apoptosis was
      greatly enhanced by BSO, blocked by NAC, and accompanied by poly(ADP-ribose)
      polymerase cleavage and activation of caspase-3, caspase-8, and caspase-9. We
      measured BAX conformational change and mitochondrial membrane potential, and
      using mouse embryonic fibroblast (MEF) Bax/Bak double knockouts (MEF(Bax-/-/Bak-/
      )), we found that apoptosis was mediated through mitochondrial pathways, but
      dependent on caspases in both cell lines and patient samples. CONCLUSIONS:
      Andrographolide caused ROS-dependent apoptosis in lymphoma cell lines and in
      primary tumor samples, which was enhanced by depletion of GSH and inhibited by
      NAC or the pan-caspase inhibitor Z-VAD-FMK. Further studies of diterpenoid
      lactones in lymphoma are warranted.

PMID- 20798231
TI  - Human artificial chromosome with a conditional centromere for gene delivery and
      gene expression.
AB  - Human artificial chromosomes (HACs), which carry a fully functional centromere
      and are maintained as a single-copy episome, are not associated with random
      mutagenesis and offer greater control over expression of ectopic genes on the
      HAC. Recently, we generated a HAC with a conditional centromere, which includes
      the tetracycline operator (tet-O) sequence embedded in the alphoid DNA array.
      This conditional centromere can be inactivated, loss of the alphoid(tet-O) (tet-O
      HAC) by expression of tet-repressor fusion proteins. In this report, we describe
      adaptation of the tet-O HAC vector for gene delivery and gene expression in human
      cells. A loxP cassette was inserted into the tet-O HAC by homologous
      recombination in chicken DT40 cells following a microcell-mediated chromosome
      transfer (MMCT). The tet-O HAC with the loxP cassette was then transferred into
      Chinese hamster ovary cells, and EGFP transgene was efficiently and accurately
      incorporated into the tet-O HAC vector. The EGFP transgene was stably expressed
      in human cells after transfer via MMCT. Because the transgenes inserted on the
      tet-O HAC can be eliminated from cells by HAC loss due to centromere
      inactivation, this HAC vector system provides important novel features and has
      potential applications for gene expression studies and gene therapy.

PMID- 20798232
TI  - Survival and prognostic factors in malignant pleural mesothelioma: a
      retrospective study of 314 patients in the west part of Japan.
AB  - OBJECTIVE: The objective in our study was to examine baseline and other
      characteristics associated with survival in patients with malignant pleural
      mesothelioma in Japan. METHODS: Three hundred and fourteen patients with an
      adjudicated diagnosis of mesothelioma were examined. Survival was evaluated by
      the Kaplan-Meier method with the log-rank test. The Cox model was used to
      estimate the hazard ratio for the possible prognostic factors. RESULTS: Of 314
      patients, 223 (71%) died and only 40 (13%) were still alive at the end of the
      observation period starting from the day of diagnosis, while 51 (16%) were
      transferred to other hospitals or had the last health service contact before the
      end of the study period yielding the median survival of 308 days. In the
      multivariate analysis, age older than 70 years (hazard ratio = 2.17; 95%
      confidence interval, 1.36-3.46), non-epithelioid type (hazard ratio = 1.58; 95%
      confidence interval, 1.15-2.18), poor performance status (hazard ratio = 3.22;
      95% confidence interval, 1.19-8.74), high white blood cell count (hazard ratio =
      1.49; 95% confidence interval, 0.99-2.26) and high C-reactive protein level
      (hazard ratio = 1.80; 95% confidence interval, 1.06-3.06) were negatively
      associated with survival, after adjustment for other factors. CONCLUSIONS: Some
      baseline conditions including old age, poor performance status, non-epithelioid
      type, high white blood cell count and high C-reactive protein level were
      determinants of poor survival of patients with malignant mesothelioma.

PMID- 20798233
TI  - TIMP-3 recruits quiescent hematopoietic stem cells into active cell cycle and
      expands multipotent progenitor pool.
AB  - Regulating transition of hematopoietic stem cells (HSCs) between quiescent and
      cycling states is critical for maintaining homeostasis of blood cell production.
      The cycling states of HSCs are regulated by the extracellular factors such as
      cytokines and extracellular matrix; however, the molecular circuitry for such
      regulation remains elusive. Here we show that tissue inhibitor of
      metalloproteinase-3 (TIMP-3), an endogenous regulator of metalloproteinases,
      stimulates HSC proliferation by recruiting quiescent HSCs into the cell cycle.
      Myelosuppression induced TIMP-3 in the bone marrow before hematopoietic recovery.
      Interestingly, TIMP-3 enhanced proliferation of HSCs and promoted expansion of
      multipotent progenitors, which was achieved by stimulating cell-cycle entry of
      quiescent HSCs without compensating their long-term repopulating activity.
      Surprisingly, this effect did not require metalloproteinase inhibitory activity
      of TIMP-3 and was possibly mediated through a direct inhibition of angiopoietin-1
      signaling, a critical mediator for HSC quiescence. Furthermore, bone marrow
      recovery from myelosuppression was accelerated by over-expression of TIMP-3, and
      in turn, impaired in TIMP-3-deficient animals. These results suggest that TIMP-3
      may act as a molecular cue in response to myelosuppression for recruiting dormant
      HSCs into active cell cycle and may be clinically useful for facilitating
      hematopoietic recovery after chemotherapy or ex vivo expansion of HSCs.

PMID- 20798234
TI  - Early mammalian erythropoiesis requires the Dot1L methyltransferase.
AB  - Histone methylation is an important regulator of gene expression; its coordinated
      activity is critical in complex developmental processes such as hematopoiesis.
      Disruptor of telomere silencing 1-like (DOT1L) is a unique histone
      methyltransferase that specifically methylates histone H3 at lysine 79. We
      analyzed Dot1L-mutant mice to determine influence of this enzyme on embryonic
      hematopoiesis. Mutant mice developed more slowly than wild-type embryos and died
      between embryonic days 10.5 and 13.5, displaying a striking anemia, especially
      apparent in small vessels of the yolk sac. Further, a severe, selective defect in
      erythroid, but not myeloid, differentiation was observed. Erythroid progenitors
      failed to develop normally, showing retarded progression through the cell cycle,
      accumulation during G0/G1 stage, and marked increase in apoptosis in response to
      erythroid growth factors. GATA2, a factor essential for early erythropoiesis, was
      significantly reduced in Dot1L-deficient cells, whereas expression of PU.1, a
      transcription factor that inhibits erythropoiesis and promotes myelopoiesis, was
      increased. These data suggest a model whereby DOT1L-dependent lysine 79 of
      histone H3 methylation serves as a critical regulator of a differentiation switch
      during early hematopoiesis, regulating steady-state levels of GATA2 and PU.1
      transcription, thus controlling numbers of circulating erythroid and myeloid
      cells.

PMID- 20798235
TI  - Serum immunoglobulin free light-chain measurement in primary amyloidosis:
      prognostic value and correlations with clinical features.
AB  - Immunoglobulin free light chains (FLCs) are the precursors of amyloid fibrils in
      primary amyloidosis (AL). We studied the relationship between FLC levels and
      clinical features in 730 patients with newly diagnosed AL. The plasma cell clone
      was lambda in 72% patients, and kappa in 28% patients. kappa-AL had more GI tract
      and liver involvement, where as renal involvement was more with lambda-AL. While
      the overall survival (OS) was similar for kappa and lambda-AL, the median OS for
      those without an identifiable serum heavy chain was significantly shorter (12.6
      vs 29.9 months; P = .02). The OS was shorter among those with a higher dFLC
      (involved FLC-uninvolved FLC; kappa > 29.4 mg/dL or lambda > 18.2 mg/dL using
      median for cutoff); 10.9 vs 37.1 months; P < .001. In multivariate analysis, dFLC
      was independent of other prognostic factors. The type of light chain impacts the
      spectrum of organ involvement and the FLC burden correlates with survival in AL.

PMID- 20798236
TI  - Photodepletion differentially affects CD4+ Tregs versus CD4+ effector T cells
      from patients with chronic graft-versus-host disease.
AB  - Even the most potent immunosuppressive drugs often fail to control graft-versus
      host disease (GVHD), the most frequent and deleterious posttransplantation
      complication. We previously reported that photodepletion using dibromorhodamine
      (TH9402) eliminates T cells from healthy donors activated against major
      histocompatibility complex-incompatible cells and spares resting T cells. In the
      present study, we identified photodepletion conditions selectively eradicating
      endogenous proliferating T cells from chronic GVHD patients, with the
      concomittant sparing and expansion of CD4(+)CD25(+) forkhead box protein 3
      positive T cells. The regulatory T-cell (Treg) nature and function of these
      photodepletion-resistant cells was demonstrated in coculture and
      depletion/repletion experiments. The mechanism by which Tregs escape
      photodepletion involves active P-glycoprotein-mediated drug efflux. This Treg
      inhibitory activity is attributable to interleukin-10 secretion, requires cell
      cell contact, and implies binding with cytotoxic T-lymphocyte antigen 4 (CTLA-4).
      Preventing CTLA-4 ligation abrogated the in vitro generation of Tregs, thus
      identifying CTLA-4-mediated cell-cell contact as a crucial priming event for Treg
      function. Moreover, the frequency of circulating Tregs increased in chronic GVHD
      patients treated with TH9402 photodepleted cells. In conclusion, these results
      identify a novel approach to both preserve and expand Tregs while selectively
      eliminating CD4(+) effector T cells. They also uncover effector pathways that
      could be used advantageously for the treatment of patients with refractory GVHD.

PMID- 20798237
TI  - Adenosine A2A receptors induced on iNKT and NK cells reduce pulmonary
      inflammation and injury in mice with sickle cell disease.
AB  - We showed previously that pulmonary function and arterial oxygen saturation in
      NY1DD mice with sickle cell disease (SCD) are improved by depletion of invariant
      natural killer T (iNKT) cells or blockade of their activation. Here we
      demonstrate that SCD causes a 9- and 6-fold induction of adenosine A(2A) receptor
      (A(2A)R) mRNA in mouse pulmonary iNKT and natural killer (NK) cells,
      respectively. Treating SCD mice with the A(2A)R agonist ATL146e produced a dose
      dependent reversal of pulmonary dysfunction with maximal efficacy at 10
      ng/kg/minute that peaked within 3 days and persisted throughout 7 days of
      continuous infusion. Crossing NY1DD mice with Rag1(-/-) mice reduced pulmonary
      injury that was restored by adoptive transfer of 10(6) purified iNKT cells.
      Reconstituted injury was reversed by ATL146e unless the adoptively transferred
      iNKT cells were pretreated with the A(2A)R alkylating antagonist, FSPTP (5-amino
      7-[2-(4-fluorosulfonyl)phenylethyl]-2-(2-furyl)-pryazolo[4,3-epsilon]-1,2,4
      triazolo[1,5-c]pyrimidine), which completely prevented pro-tection. In NY1DD mice
      exposed to hypoxia-reoxygenation, treatment with ATL146e at the start of
      reoxygenation prevented further lung injury. Together, these data indicate that
      activation of induced A(2A)Rs on iNKT and NK cells in SCD mice is sufficient to
      improve baseline pulmonary function and prevent hypoxia-reoxygenation-induced
      exacerbation of pulmonary injury. A(2A) agonists have promise for treating
      diseases associated with iNKT or NK cell activation.

PMID- 20798238
TI  - PIDs and cancer: an evolving story.

PMID- 20798239
TI  - A new window on c-Myb function.

PMID- 20798240
TI  - Remission in CML: is DNA useful?

PMID- 20798241
TI  - A snappy new concept for APS.

PMID- 20798242
TI  - PLDing a case for angiogenesis.

PMID- 20798244
TI  - Thymus-derived glucocorticoids mediate androgen effects on thymocyte homeostasis.
AB  - Androgens contribute to the involution process of the aging thymus gland.
      However, molecular mechanisms behind this effect remain largely unknown. We have
      investigated the influence of testosterone on the ectopic synthesis of
      glucocorticoids (GCs) in thymocytes, an activity recently shown by us to be
      important for the homeostatic regulation of these cells. Castration, which leads
      to a strong increase in thymus tissue and function, was associated with a reduced
      GC release from thymocytes caused by down-regulated expression of several enzymes
      involved in GC synthesis, without affecting GC synthesis in the adrenals.
      Testosterone treatment of castrated male mice reversed these effects, also
      without affecting adrenal GC synthesis. The effects of testosterone in castrated
      mice on thymocyte homeostasis and GC release were strongly reduced in mice
      pretreated with the CYP11B1 enzyme inhibitor metyrapone, acting on the last step
      in the corticosterone synthesis. The androgen-induced thymic involution was
      dependent on GC action, because this was completely absent in mice lacking GC
      receptor (GR) expression specifically in thymocytes. We provide here an
      unrecognized mechanism how androgens contribute to thymic involution by
      stimulating local synthesis and release of GCs in the thymus.

PMID- 20798245
TI  - Regulation of intermediary metabolism by the PKCdelta signalosome in
      mitochondria.
AB  - PKCdelta has emerged as a novel regulatory molecule of oxidative phosphorylation
      by targeting the pyruvate dehydrogenase complex (PDHC). We showed that activation
      of PKCdelta leads to the dephosphorylation of pyruvate dehydrogenase kinase 2
      (PDK2), thereby decreasing PDK2 activity and increasing PDH activity,
      accelerating oxygen consumption, and augmenting ATP synthesis. However, the
      molecular components that mediate PKCdelta signaling in mitochondria have
      remained elusive so far. Here, we identify for the first time a functional
      complex, which includes cytochrome c as the upstream driver of PKCdelta, and uses
      the adapter protein p66Shc as a platform with vitamin A (retinol) as a fourth
      partner. All four components are necessary for the activation of the PKCdelta
      signal chain. Genetic ablation of any one of the three proteins, or retinol
      depletion, silences signaling. Furthermore, mutations that disrupt the
      interaction of cytochrome c with p66Shc, of p66Shc with PKCdelta, or the deletion
      of the retinol-binding pocket on PKCdelta, attenuate signaling. In cytochrome c
      deficient cells, reintroduction of cytochrome c Fe(3+) protein restores PKCdelta
      signaling. Taken together, these results indicate that oxidation of PKCdelta is
      key to the activation of the pathway. The PKCdelta/p66Shc/cytochrome c
      signalosome might have evolved to effect site-directed oxidation of zinc-finger
      structures of PKCdelta, which harbor the activation centers and the vitamin A
      binding sites. Our findings define the molecular mechanisms underlying the
      signaling function of PKCdelta in mitochondria.

PMID- 20798246
TI  - Key factors regulating Plasmodium berghei sporozoite survival and transformation
      revealed by an automated visual assay.
AB  - Malaria is transmitted to the host when Plasmodium sporozoites are injected by a
      mosquito vector. Sporozoites eventually enter hepatocytes, where they
      differentiate into liver-stage parasites. During the first hours after hepatocyte
      invasion, the crescent-shaped sporozoites transform into spherical intracellular
      exoerythrocytic parasites. This process, which precedes genome replication, can
      be mimicked in vitro in the absence of host cells. Here, we developed an
      automated method to follow transformation and cell death of sporozoites in vitro.
      This assay provides a rapid tool to test sporozoite survival and to screen for
      antiparasitic drugs. We found that extracellular bicarbonate and high temperature
      trigger transformation, whereas physiological serum albumin concentrations and
      media lacking bicarbonate delayed sporozoite death. Because bicarbonate also
      triggers ookinete transformation and exflagellation of gametocytes, we suggest
      that a common molecular mechanism regulates similar aspects of stage conversion
      in Plasmodium.

PMID- 20798247
TI  - Mitochondrial dysfunction and loss of Parkinson's disease-linked proteins
      contribute to neurotoxicity of manganese-containing welding fumes.
AB  - Welding generates complex metal aerosols, inhalation of which is linked to
      adverse health effects among welders. An important health concern of welding fume
      (WF) exposure is neurological dysfunction akin to Parkinson's disease (PD),
      thought to be mediated by manganese (Mn) in the fumes. Also, there is a
      proposition that welding might accelerate the onset of PD. Our recent findings
      link the presence of Mn in the WF with dopaminergic neurotoxicity seen in rats
      exposed to manual metal arc-hard surfacing (MMA-HS) or gas metal arc-mild steel
      (GMA-MS) fumes. To elucidate the molecular mechanisms further, we investigated
      the association of PD-linked (Park) genes and mitochondrial function in causing
      dopaminergic abnormality. Repeated instillations of the two fumes at doses that
      mimic ~1 to 5 yr of worker exposure resulted in selective brain accumulation of
      Mn. This accumulation caused impairment of mitochondrial function and loss of
      tyrosine hydroxylase (TH) protein, indicative of dopaminergic injury. A
      fascinating finding was the altered expression of Parkin (Park2), Uchl1 (Park5),
      and Dj1 (Park7) proteins in dopaminergic brain areas. A similar regimen of
      manganese chloride (MnCl(2)) also caused extensive loss of striatal TH,
      mitochondrial electron transport components, and Park proteins. As mutations in
      PARK genes have been linked to early-onset PD in humans, and because welding is
      implicated as a risk factor for parkinsonism, PARK genes might play a critical
      role in WF-mediated dopaminergic dysfunction. Whether these molecular alterations
      culminate in neurobehavioral and neuropathological deficits reminiscent of PD
      remains to be ascertained.

PMID- 20798248
TI  - Post-transcriptional regulation of heparanase gene expression by a 3' AU-rich
      element.
AB  - Heparanase up-regulation was documented in an increasing number of human
      carcinomas, associated with poor prognosis. The purpose of the current study was
      to identify mechanisms responsible for heparanase induction. We provide evidence
      that heparanase expression is regulated at the post-transcriptional level by
      sequences at the 3' untranslated region (3' UTR) of the gene. Constructing the 3'
      UTR immediately following the heparanase cDNA reduces heparanase enzymatic
      activity and protein levels, resulting in decreased cellular invasion capacity.
      We further identified a 185-bp sequence within the 3' UTR that mediates
      heparanase down-regulation, and characterized an adenine (A)/uracil (U)-rich
      consensus element (ARE) within this region. Deletion of the entire 185-bp region
      or the ARE eliminated the inhibitory effect of the 3' UTR, resulting in elevated
      heparanase levels and formation of larger tumor xenografts indistinguishable from
      those produced by heparanase-overexpressing cells in terms of size,
      vascularization, and Akt activation. These results suggest that loss of the ARE
      is an important regulatory mechanism contributing to heparanase induction in
      human cancer.

PMID- 20798249
TI  - Percutaneous treatment of thrombosed arteriovenous fistulas: clinical and
      economic implications.
AB  - BACKGROUND AND OBJECTIVES: Maintenance of previously thrombosed arteriovenous
      fistulas (AVFs) as functional vascular accesses can be highly expensive, with
      relevant financial implications for healthcare systems. The aim of our study was
      to evaluate the costs and health outcomes of vascular access care in hemodialysis
      patients with AVF thrombosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A
      retrospective, controlled cohort study was performed among local hemodialysis
      patients with completely thrombosed AVFs between August 1, 2007, and July 1,
      2008. Detailed clinical and demographic information was collected and a
      comprehensive measure of total vascular access costs was obtained. Costs are
      reported in 2009 U.S. dollars. RESULTS: A total of 63 consecutive hemodialysis
      patients with thrombosed AVFs were identified--a cohort of 37 patients treated
      with percutaneous thrombectomy and a historic cohort of 25 patients with
      abandoned thrombosed AVFs. The mean cost of all vascular access care at 6 months
      was $2479. Salvage of thrombosed AVFs led to a near two-fold reduction in access
      related expenses, per patient-month at risk ($375 versus $706; P = 0.048). The
      costs for access-related hospitalizations ($393 versus $91; P = 0.050),
      management of access dysfunction ($106 versus $28; P = 0.005), and surgical
      interventions ($35 versus $6; P = 0.001) were also significantly lower in the
      percutaneous treatment group. At 6 months, most of these patients had a
      functional AVF as permanent vascular access (91% versus 33%, P = 0.0001).
      CONCLUSIONS: Salvage of thrombosed AVF is a highly efficient procedure;
      therefore, intensive efforts should be undertaken to universalize these
      interventions.

PMID- 20798250
TI  - The interplay of socioeconomic status, distance to center, and interdonor service
      area travel on kidney transplant access and outcomes.
AB  - BACKGROUND AND OBJECTIVES: Variation in kidney transplant access across the
      United States may motivate relocation of patients with ability to travel to
      better-supplied areas. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We examined
      national transplant registry and U.S. Census data for kidney transplant
      candidates listed in 1999 to 2009 with a reported residential zip code (n =
      203,267). Cox's regression was used to assess associations of socioeconomic
      status (SES), distance from residence to transplant center, and relocation to a
      different donation service area (DSA) with transplant access and outcomes.
      RESULTS: Patients in the highest SES quartile had increased access to transplant
      compared with those with lowest SES, driven strongly by 76% higher likelihood of
      living donor transplantation (adjusted hazard ratio [aHR] 1.76, 95% confidence
      interval [CI] 1.70 to 1.83). Waitlist death was reduced in high compared with low
      SES candidates (aHR 0.86, 95% CI 0.84 to 0.89). High SES patients also
      experienced lower mortality after living and deceased donor transplant. Patients
      living farther from the transplant center had reduced access to deceased donor
      transplant and increased risk of post-transplant death. Inter-DSA travel was
      associated with a dramatic increase in deceased donor transplant access (HR 1.94,
      95% CI 1.88 to 2.00) and was predicted by high SES, white race, and longer
      deceased-donor allograft waiting time in initial DSA. CONCLUSIONS: Ongoing
      disparities exist in kidney transplantation access and outcomes on the basis of
      geography and SES despite near-universal insurance coverage under Medicare. Inter
      DSA travel improves access and is more common among high SES candidates.

PMID- 20798251
TI  - Cinacalcet effectively reduces parathyroid hormone secretion and gland volume
      regardless of pretreatment gland size in patients with secondary
      hyperparathyroidism.
AB  - BACKGROUND AND OBJECTIVES: Cinacalcet is effective in reducing serum parathyroid
      hormone (PTH) in patients with secondary hyperparathyroidism. However, it has not
      been proven whether parathyroid gland size predicts response to therapy and
      whether cinacalcet is capable of inducing a reduction in parathyroid volume.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This 52-week, multicenter, open
      label study enrolled hemodialysis patients with moderate to severe secondary
      hyperparathyroidism (intact PTH >300 pg/ml). Doses of cinacalcet were adjusted
      between 25 and 100 mg to achieve intact PTH <180 pg/ml. Ultrasonography was
      performed to measure the parathyroid gland size at baseline, week 26, and week
      52. Findings were also compared with those of historical controls. RESULTS: Of
      the 81 subjects enrolled, 56 had parathyroid glands smaller than 500 mm(3) (group
      S) and 25 had at least one enlarged gland larger than 500 mm(3) (group L).
      Treatment with cinacalcet effectively decreased intact PTH by 55% from baseline
      in group S and by 58% in group L. A slightly greater proportion of patients in
      group S versus group L achieved an intact PTH <180 pg/ml (46 versus 32%) and a
      >30% reduction from baseline (88 versus 78%), but this was not statistically
      significant. Cinacalcet therapy also resulted in a significant reduction in
      parathyroid gland volume regardless of pretreatment size, which was in sharp
      contrast to historical controls (n = 87) where parathyroid gland volume
      progressively increased with traditional therapy alone. CONCLUSIONS: Cinacalcet
      effectively decreases serum PTH levels and concomitantly reduces parathyroid
      gland volume, even in patients with marked parathyroid hyperplasia.

PMID- 20798253
TI  - Damned if you do, damned if you don't: potassium binding resins in hyperkalemia.
AB  - Sodium polystyrene sulfonate (SPS) potassium binding resins increase colonic
      potassium excretion and are approved by the U.S. Food and Drug Administration
      (FDA) for the treatment of hyperkalemia. In 2009, the FDA recommended that
      sorbitol, a cathartic often given with SPS to prevent obstipation, not be added
      to SPS powder because of associated colonic necrosis. A premixed oral suspension
      of SPS in 33% sorbitol was not included in this warning. SPS resins increase
      stool potassium excretion in normokalemic subjects, but proportionately more
      potassium is excreted due to cathartics when the two are combined. In
      hyperkalemic patients, oral SPS mixed in water significantly decreases serum
      potassium within 24 hours. SPS/sorbitol-associated colonic necrosis is most
      commonly seen in patients who have received enemas in the setting of recent
      abdominal surgery, bowel injury, or intestinal dysfunction. It is a rare event,
      on the order of 0.2 to 0.3%, almost exclusively present in patients at risk. The
      agent most likely associated with colonic necrosis is 70% sorbitol, and animal
      data support that etiology. There is very little data to suggest that oral SPS
      given with 33% sorbitol (in the premixed form) or SPS powder in water orally or
      as an enema causes colonic necrosis. SPS ion-exchange resins are the only agents,
      other than dialysis and diuretics, available to increase potassium excretion in
      hyperkalemia, and when used appropriately, they appear to be clinically effective
      and reasonably safe.

PMID- 20798252
TI  - Immunosuppression and renal outcome in congenital and pediatric steroid-resistant
      nephrotic syndrome.
AB  - BACKGROUND AND OBJECTIVES: Mutations in podocyte genes are associated with
      steroid-resistant nephrotic syndrome (SRNS), mostly affecting younger age groups.
      To date, it is unclear whether these patients benefit from intensified
      immunosuppression with cyclosporine A (CsA). The aim of this study was to
      evaluate the influence of podocyte gene defects in congenital nephrotic syndrome
      (CNS) and pediatric SRNS on the efficacy of CsA therapy and preservation of renal
      function. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: Genotyping was
      performed in 91 CNS/SRNS patients, irrespective of age at manifestation or
      response to CsA. RESULTS: Mutations were identified in 52% of families (11 NPHS1,
      17 NPHS2, 11 WT1, 1 LAMB2, 3 TRPC6). Sixty-eight percent of patients with
      nongenetic SRNS responded to CsA, most of them achieved complete remission. In
      contrast, none of the patients with genetic CNS/SRNS experienced a complete
      remission and only two (17%) achieved a partial response, both affected by a WT1
      mutation. Preservation of renal function was significantly better in children
      with nongenetic disease after a mean follow-up time of 8.6 years (ESRD in 29%
      versus 71%). CONCLUSIONS: The mutation detection rate in our population was high
      (52%). Most patients with genetic CNS/SRNS did not benefit from CsA with
      significantly lower response rates compared with nongenetic patients and showed
      rapid progression to end-stage renal failure. These data strongly support the
      idea not to expose CNS/SRNS patients with inherited defects related to podocyte
      function to intensified immunosuppression with CsA.

PMID- 20798254
TI  - The evidence-based use of thiazide diuretics in hypertension and nephrolithiasis.
AB  - Thiazide-type diuretics are commonly used in the treatment of hypertension and
      nephrolithiasis. Evidence from randomized clinical trials needs to be considered
      in decisions about agent choice and dose. In nephrolithiasis, one of the major
      limitations of the literature is a paucity of data on the dose-response effect of
      hydrochlorothiazide (HCTZ) on urinary calcium excretion. The best available
      evidence for prevention of stone recurrence suggests the use of indapamide at 2.5
      mg/d, chlorthalidone at 25 to 50 mg daily, or HCTZ 25 mg twice a day or 50 mg
      daily. In hypertension, chlorthalidone (12.5 to 30 mg daily) may be the best
      choice when a diuretic is used for initial therapy, with indapamide (1.5 mg
      daily) being a valuable alternative for older patients. When adding a thiazide to
      other drug classes, indapamide (2.5 mg daily) has demonstrated value in
      hypertensive patients who have had a stroke, and HCTZ (12.5 to 25 mg daily) has a
      safe track record in several patient groups. Although chlorthalidone has not been
      tested as add-on therapy, the authors believe it is a safe option in such cases.

PMID- 20798255
TI  - Efficacy and safety of treatment with rituximab for difficult steroid-resistant
      and -dependent nephrotic syndrome: multicentric report.
AB  - BACKGROUND AND OBJECTIVES: The treatment of idiopathic nephrotic syndrome is
      often complicated by a refractory and relapsing course, with risk of drug
      toxicity and progressive renal failure. We report the efficacy and safety of
      rituximab in patients with steroid-resistant (SRNS) and steroid-dependent
      nephrotic syndrome (SDNS) refractory to standard therapy. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: This was a cohort study in academic, tertiary care
      centers in India and the United States. Patients with SRNS or SDNS, not
      responding to medications or showing calcineurin inhibitor toxicity, treated with
      two to four doses of intravenous rituximab, and followed >=12 months were
      included. Remission was termed as complete, partial, or no response. RESULTS:
      Thirty-three patients with SRNS (24 initial, 9 late resistance) and 24 with SDNS,
      with mean ages of 12.7 +/- 9.1 and 11.7 +/- 2.9 years, respectively, were
      included. Six months after rituximab therapy, 9 (27.2%) patients with SRNS showed
      complete remission, 7 (21.2%) had partial remission, and 17 (51.5%) had no
      response. At 21.5 +/- 11.5 months, remission was sustained in 15 (complete: 7,
      partial: 8) patients. Of 24 patients with SDNS, remission was sustained in 20
      (83.3%) at 12 months and in 17 (71%) at follow-up of 16.8 +/- 5.9 months. The
      mean difference in relapses before and 12 months after treatment with rituximab
      was 3.9 episodes/patient per year. CONCLUSIONS: Therapy with rituximab was safe
      and effective in inducing and maintaining remission in a significant proportion
      of patients with difficult SRNS and SDNS.

PMID- 20798256
TI  - Detection of peripheral artery disease by duplex ultrasonography among
      hemodialysis patients.
AB  - BACKGROUND AND OBJECTIVES: Peripheral arterial disease (PAD) is a known predictor
      of cardiovascular morbidity and mortality among hemodialysis patients. Although
      ankle-brachial BP index (ABI) is a simple and reliable test for PAD screening,
      its sensitivity has been suggested to decrease among dialysis patients. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a cross-sectional outpatient
      cohort study to examine prevalence of PAD among hemodialysis patients using
      duplex ultrasonography of the lower extremity artery. We also evaluate the
      influence of increased arterial stiffness on impaired accuracy of ABI for PAD
      screening. RESULTS: Of 315 total patients, 23.8% had PAD. PAD was associated with
      younger age, diabetes, current smoking, atherosclerotic comorbidities, increased
      total cholesterol levels, increased triglyceride levels, and lower Kt/V. The
      receiver operating characteristic analysis (area under the receiver operating
      characteristic curve = 0.846) showed that sensitivity and specificity of ABI
      values for PAD were 49.0 and 94.8%, respectively. An ABI cut-off value of 1.05
      resulted in the best sensitivity (74.5%) and specificity (84.4%). There was a
      significant difference in sensitivity of ABI levels <0.9 for detecting PAD among
      patients in different brachial-ankle pulse wave velocity quartiles. In patients
      with the highest brachial-ankle pulse wave velocity quartile, PAD was most
      prevalent (46.5%), and ABI had the highest accuracy in detecting PAD (area under
      the curve, 0.933). CONCLUSIONS: These results suggest that duplex ultrasonography
      was a useful tool for screening asymptomatic PAD among hemodialysis patients and
      that the diagnostic value of ABI for PAD was affected by various factors.

PMID- 20798257
TI  - Reciprocal control of 1,25-dihydroxyvitamin D and FGF23 formation involving the
      FGF23/Klotho system.
AB  - Fibroblast growth factor 23 (FGF23) is a circulating hormone that is synthesized
      by osteocytes and osteoblasts. This glycosylated peptide controls phosphate
      balance by modulating urinary phosphate excretion and indirectly intestinal
      phosphate absorption by reducing expression of the renal and intestinal sodium
      phosphate transporters. In a feedback loop, 1,25-dihydroxyvitamin D and phosphate
      intake control FGF23 production. FGF23 is inactivated by cleavage by a still
      unidentified enzyme. FGF23 cleavage occurs within cells and probably in the
      circulation. Klotho, a protein expressed at the cell surface of few organs, forms
      complexes with FGF receptors, which increases their affinity for FGF23. Klotho is
      also released into the plasma and urine by an enzymatic cleavage. FGF23 plays a
      central role in vitamin D metabolism: It inhibits calcitriol synthesis in the
      kidney and stimulates the catabolism of active vitamin D sterols. In turn,
      calcitriol stimulates FGF23 and Klotho expression. In chronic kidney diseases,
      FGF23 concentration increases as GFR declines, whereas Klotho tissue expression
      decreases. The modifications of FGF23 and Klotho expression are probably involved
      in the genesis of hyperparathyroidism and the resistance to vitamin D receptor
      (VDR) activation in chronic kidney disease. Low vitamin D, high FGF23
      concentrations, and defects in VDR activation are associated with similar risks,
      which evoke the possibility that potential FGF23 toxicity might be partly
      mediated by FGF23-induced decrease in calcitriol or 25-hydroxyvitamin D.
      Conversely, VDR activators could be used to modulate Klotho or FGF23 expression.

PMID- 20798258
TI  - Urinary biomarkers in the clinical prognosis and early detection of acute kidney
      injury.
AB  - BACKGROUND AND OBJECTIVES: Several novel urinary biomarkers have shown promise in
      the early detection and diagnostic evaluation of acute kidney injury (AKI).
      Clinicians have limited tools to determine which patients will progress to more
      severe forms of AKI at the time of serum creatinine increase. The diagnostic and
      prognostic utility of novel and traditional AKI biomarkers was evaluated during a
      prospective study of 123 adults undergoing cardiac surgery. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Urinary neutrophil gelatinase-associated lipocalin
      (NGAL), cystatin C (CyC), kidney injury molecule-1 (KIM-1), hepatocyte growth
      factor (HGF), pi-glutathione-S-transferase (pi-GST), alpha-GST, and fractional
      excretions of sodium and urea were all measured at preoperative baseline,
      postoperatively, and at the time of the initial clinical diagnosis of AKI.
      Receiver operator characteristic curves were generated and the areas under the
      curve (AUCs) were compared. RESULTS: Forty-six (37.4%) subjects developed AKI
      Network stage 1 AKI; 9 (7.3%) of whom progressed to stage 3. Preoperative KIM-1
      and alpha-GST were able to predict the future development of stage 1 and stage 3
      AKI. Urine CyC at intensive care unit (ICU) arrival best detected early stage 1
      AKI (AUC = 0.70, P < 0.001); the 6-hour ICU NGAL (AUC = 0.88; P < 0.001) best
      detected early stage 3 AKI. pi-GST best predicted the progression to stage 3 AKI
      at the time of creatinine increase (AUC = 0.86; P = 0.002). CONCLUSION: Urinary
      biomarkers may improve the ability to detect early AKI and determine the clinical
      prognosis of AKI at the time of diagnosis.

PMID- 20798259
TI  - Cubilin is essential for albumin reabsorption in the renal proximal tubule.
AB  - Receptor-mediated endocytosis is responsible for protein reabsorption in the
      proximal tubule. This process involves two interacting receptors, megalin and
      cubilin, which form a complex with amnionless. Whether these proteins function in
      parallel or as part of an integrated system is not well understood. Here, we
      report the renal effects of genetic ablation of cubilin, with or without
      concomitant ablation of megalin, using a conditional Cre-loxP system. We observed
      that proximal tubule cells did not localize amnionless to the plasma membrane in
      the absence of cubilin, indicating a mutual dependency of cubilin and amnionless
      to form a functional membrane receptor complex. The cubilin-amnionless complex
      mediated internalization of intrinsic factor-vitamin B12 complexes, but megalin
      considerably increased the uptake. Furthermore, cubilin-deficient mice exhibited
      markedly decreased uptake of albumin by proximal tubule cells and resultant
      albuminuria. Inactivation of both megalin and cubilin did not increase
      albuminuria, indicating that the main role of megalin in albumin reabsorption is
      to drive the internalization of cubilin-albumin complexes. In contrast, cubulin
      deficiency did not affect urinary tubular uptake or excretion of vitamin D
      binding protein (DBP), which binds cubilin and megalin. In addition, we observed
      cubilin-independent reabsorption of the "specific" cubilin ligands transferrin,
      CC16, and apoA-I, suggesting a role for megalin and perhaps other receptors in
      their reabsorption. In summary, with regard to albumin, cubilin is essential for
      its reabsorption by proximal tubule cells, and megalin drives internalization of
      cubilin-albumin complexes. These genetic models will allow further analysis of
      protein trafficking in the progression of proteinuric renal diseases.

PMID- 20798261
TI  - Matrix remodeling in vascular calcification associated with chronic kidney
      disease.
AB  - Vascular calcification is a major contributor to cardiovascular disease, a
      leading cause of death in patients with chronic kidney disease. Mechanistic
      studies highlight the importance of dysregulated mineral metabolism, vascular
      osteochondrogenic processes, apoptosis, and deficiencies in calcification
      inhibitors as potential mediators of calcification in renal disease. However, the
      contribution of the extracellular matrix in vascular calcification associated
      with chronic kidney disease is less understood. Here we examine evidence that
      suggests important roles for elastin and elastin-degrading enzymes as potential
      key regulators of calcification. Additional studies aimed at further
      understanding their role are critical for the design of therapeutic
      interventions.

PMID- 20798260
TI  - Deletion of the pH sensor GPR4 decreases renal acid excretion.
AB  - Proton receptors are G protein-coupled receptors that accept protons as ligands
      and function as pH sensors. One of the proton receptors, GPR4, is relatively
      abundant in the kidney, but its potential role in acid-base homeostasis is
      unknown. In this study, we examined the distribution of GPR4 in the kidney, its
      function in kidney epithelial cells, and the effects of its deletion on acid-base
      homeostasis. We observed GPR4 expression in the kidney cortex, in the outer and
      inner medulla, in isolated kidney collecting ducts, and in cultured outer and
      inner medullary collecting duct cells (mOMCD1 and mIMCD3). Cultured mOMCD1 cells
      exhibited pH-dependent accumulation of intracellular cAMP, characteristic of GPR4
      activation; GPR4 knockdown attenuated this accumulation. In vivo, deletion of
      GPR4 decreased net acid secretion by the kidney and resulted in a nongap
      metabolic acidosis, indicating that GPR4 is required to maintain acid-base
      homeostasis. Collectively, these findings suggest that GPR4 is a pH sensor with
      an important role in regulating acid secretion in the kidney collecting duct.

PMID- 20798262
TI  - Hemoglobin variability does not predict mortality in European hemodialysis
      patients.
AB  - Patients with CKD exhibit significant within-patient hemoglobin (Hb) level
      variability, especially with the use of erythropoiesis stimulating agents (ESAs)
      and iron. Analyses of dialysis cohorts in the United States produced conflicting
      results regarding the association of Hb variability with patient outcomes. Here,
      we determined Hb variability in 5037 European hemodialysis (HD) patients treated
      over 2 years to identify predictors of high variability and to evaluate its
      association with all-cause and cardiovascular disease (CVD) mortality. We
      assessed Hb variability with various methods using SD, residual SD, time-in
      target (11.0 to 12.5 g/dl), fluctuation across thresholds, and area under the
      curve (AUC). Hb variability was significantly greater among incident patients
      than prevalent patients. Compared with previously described cohorts in the United
      States, residual SD was similar but fluctuations above target were less frequent.
      Using logistic regression, age, body mass index, CVD history, dialysis vintage,
      serum albumin, Hb, angiotensin-converting enzyme (ACE) inhibitor or angiotensin
      receptor blocker (ARB) use, ESA use, dialysis access type, dialysis access
      change, and hospitalizations were significant predictors of high variability.
      Multivariable adjusted Cox regression showed that SD, residual SD, time-in
      target, and AUC did not predict all-cause or CVD mortality during a median follow
      up of 12.4 months (IQR: 7.7 to 17.4). However, patients with consistently low
      levels of Hb (<11 g/dl) and those who fluctuated between the target range and <11
      g/dl had increased risks for death (RR 2.34; 95% CI: 1.24 to 4.41 and RR 1.74;
      95% CI: 1.00 to 3.04, respectively). In conclusion, although Hb variability is
      common in European HD patients, it does not independently predict mortality.

PMID- 20798263
TI  - Vernalization response of Phleum pratense and its relationships to stem
      lignification and floral transition.
AB  - BACKGROUND: Timothy is a long-day grass species well adapted for cultivation in
      northern latitudes. It produces elongating tillers not only in spring growth but
      also later in summer. As the quantity and quality of harvested biomass is
      dictated by canopy architecture and the proportion of stem-forming flowering
      tillers, the regulation of flowering is of great interest in forage grass
      production. METHODS: Canopy architecture, stem morphology and freezing tolerance
      of vernalized timothy were investigated in greenhouse and field experiments. The
      molecular control of development was examined by analysing the relationship
      between apex development and expression of timothy homologues of the floral
      inducer VRN1 and repressor VRN2. KEY RESULTS: True stem formation and
      lignification of the sclerenchyma ring occur in both vernalized and regrowing
      stems irrespective of the developmental stage of the apex. The stems had,
      however, divergent morphology. Vernalization enhanced flowering, and the
      expression of the VRN1 homologue was elevated when the apex had passed into the
      reproductive stage. High VRN1 homologue expression was not associated with
      reduction in freezing tolerance and the expression coincided with increased
      levels of the floral repressor VRN2 homologue. Field experiments supported the
      observed linkage between the upregulation of the VRN1 homologue and the
      transition to the reproductive stage in vernalized tillers. The upregulation of
      putative VRN1 or VRN2 genes was restricted to vernalized tillers in the spring
      yield and, thus, not detected in non-vernalized tillers of the second yield; so
      called regrowth. CONCLUSIONS: The formation of a lignified sclerenchyma ring that
      efficiently reduces the digestibility of the stem was not related to apex
      development but rather to a requirement for mechanical support. The observed good
      freezing tolerance of reproductive timothy tillers could be one important
      adaptation mechanism ensuring high yields in northern conditions. Both VRN1 and
      VRN2 homologues required a vernalization signal for expression so the development
      of yield-forming tillers in regrowth was regulated independently of the studied
      genes.

PMID- 20798264
TI  - The complexity of the treatment: the decision-making process among women with
      rheumatoid arthritis.
AB  - There are effective medications available for the treatment of rheumatoid
      arthritis (RA); yet, medication adherence remains a problem. In this study,
      grounded theory methodology was used to investigate the decision-making process
      used by 30 women with RA when deciding to participate in an evidence-based
      treatment regimen for this disease. From the study findings, a four-phase process
      was identified. Pain, life functioning, and exhaustion of health care resources
      are the components of the initial phase, decision initiation. During knowledge
      acquisition, the second phase, patients attain information about RA and
      medications used for its treatment from varying sources. The third phase,
      trusting the health care provider, is defined by a trusting relationship between
      patients and health care providers. Patients decide to take or not take
      medications for RA during the final phase, decision is made. The participating
      women with RA used a complex decision-making process when deciding to take
      medications for this disease.

PMID- 20798266
TI  - Switching from contextual to tone fear conditioning and vice versa: the key role
      of the glutamatergic hippocampal-lateral septal neurotransmission.
AB  - The aim of the present experiment was to directly assess the role of the
      glutamatergic hippocampal-lateral septal (HPC-LS) neurotransmission in tone and
      contextual fear conditioning. We found that pretraining infusion of glutamatergic
      acid into the lateral septum promotes tone conditioning and concomitantly
      disrupts contextual conditioning. Infusion of glutamatergic antagonist, on the
      contrary, promotes contextual conditioning to the detriment of tone fear
      conditioning. These findings highlight the direct contribution of the
      glutamatergic HPC-LS neurotransmission to the adaptive selection among
      environmental stimuli of those that best predict the occurrence of the aversive
      event.

PMID- 20798268
TI  - Point: humans do demonstrate selective brain cooling during hyperthermia.

PMID- 20798267
TI  - Effects of type II diabetes on exercising skeletal muscle blood flow in the rat.
AB  - The purpose of the present investigation was to examine the muscle hyperemic
      response to steady-state submaximal running exercise in the Goto-Kakizaki (GK)
      Type II diabetic rat. Specifically, the hypothesis was tested that Type II
      diabetes would redistribute exercising blood flow toward less oxidative muscles
      and muscle portions of the hindlimb. GK diabetic (n = 10) and Wistar control (n =
      8, blood glucose concentration, 13.7 +/- 1.6 and 5.7 +/- 0.2 mM, respectively, P
      < 0.05) rats were run at 20 m/min on a 10% grade. Blood flows to 28 hindlimb
      muscles and muscle portions as well as the abdominal organs and kidneys were
      measured in the steady state of exercise using radiolabeled 15-MUm microspheres.
      Blood flow to the total hindlimb musculature did not differ between GK diabetic
      and control rats (161 +/- 16 and 129 +/- 15 ml.min(-1).100 g(-1), respectively, P
      = 0.18). Moreover, there was no difference in blood flow between GK diabetic and
      control rats in 20 of the individual muscles or muscle parts examined. However,
      in the other eight muscles examined that typically are comprised of a majority of
      fast-twitch glycolytic (IIb/IIdx) fibers, blood flow was significantly greater
      (i.e., ?31-119%, P < 0.05) in the GK diabetic rats. Despite previously documented
      impairments of several vasodilatory pathways in Type II diabetes these data
      provide the first demonstration that a reduction of exercising muscle blood flow
      during submaximal exercise is not an obligatory consequence of this condition in
      the GK diabetic rat.

PMID- 20798269
TI  - Heat stress attenuates the increase in arterial blood pressure during the cold
      pressor test.
AB  - The mechanisms by which heat stress impairs the control of blood pressure leading
      to compromised orthostatic tolerance are not thoroughly understood. A possible
      mechanism may be an attenuated blood pressure response to a given increase in
      sympathetic activity. This study tested the hypothesis that whole body heating
      attenuates the blood pressure response to a non-baroreflex-mediated
      sympathoexcitatory stimulus. Ten healthy subjects were instrumented for the
      measurement of integrated muscle sympathetic nerve activity (MSNA), mean arterial
      blood pressure (MAP), heart rate, sweat rate, and forearm skin blood flow.
      Subjects were exposed to a cold pressor test (CPT) by immersing a hand in an ice
      water slurry for 3 min while otherwise normothermic and while heat stressed
      (i.e., increase core temperature ~0.7 degrees C via water-perfused suit). Mean
      responses from the final minute of the CPT were evaluated. In both thermal
      conditions CPT induced significant increases in MSNA and MAP without altering
      heart rate. Although the increase in MSNA to the CPT was similar between thermal
      conditions (normothermia: Delta14.0 +/- 2.6; heat stress: Delta19.1 +/- 2.6
      bursts/min; P = 0.09), the accompanying increase in MAP was attenuated when
      subjects were heat stressed (normothermia: Delta25.6 +/- 2.3, heat stress:
      Delta13.4 +/- 3.0 mmHg; P < 0.001). The results demonstrate that heat stress can
      attenuate the pressor response to a sympathoexcitatory stimulus.

PMID- 20798270
TI  - Knockdown of metallothionein 1 and 2 does not affect atrophy or oxidant activity
      in a novel in vitro model.
AB  - Skeletal muscle atrophy is a significant health problem that results in decreased
      muscle size and function and has been associated with increases in oxidative
      stress. The molecular mechanisms that regulate muscle atrophy, however, are
      largely unknown. The metallothioneins (MT), a family of genes with antioxidant
      properties, have been found to be consistently upregulated during muscle atrophy,
      although their function during muscle atrophy is unknown. Therefore, we
      hypothesized that MT knockdown would result in greater oxidative stress and an
      enhanced atrophy response in C(2)C(12) myotubes subjected to serum reduction
      (SR), a novel atrophy-inducing stimulus. Forty-eight hours before SR, myotubes
      were transfected with small interfering RNA (siRNA) sequences designed to
      decrease MT expression. Muscle atrophy and oxidative stress were then measured at
      baseline and for 72 h following SR. Muscle atrophy was quantified by
      immunocytochemistry and myotube diameter measurements. Oxidative stress was
      measured using the fluorescent probe 5-(and-6)-carboxy-2',7'
      dichlorodihydrofluorescein. SR resulted in a significant increase in oxidative
      stress and a decrease in myotube size and protein content. However, there were no
      differences observed in the extent of muscle atrophy or oxidant activity
      following MT knockdown. We therefore conclude that the novel SR model results in
      a strong atrophy response and an increase in oxidant activity in cultured
      myotubes and that knockdown of MT does not affect that response.

PMID- 20798272
TI  - Quantitative assessment of lung microstructure in healthy mice using an MR-based
      3He lung morphometry technique.
AB  - The recently developed technique of lung morphometry using hyperpolarized (3)He
      diffusion magnetic resonance (MR) (Yablonskiy DA, Sukstanskii AL, Woods JC,
      Gierada DS, Quirk JD, Hogg JC, Cooper JD, Conradi MS. J Appl Physiol 107: 1258
      1265, 2009) permits in vivo study of lung microstructure at the alveolar level.
      Originally proposed for human lungs, it also has the potential to study small
      animals. The technique relies on theoretical developments in the area of gas
      diffusion in lungs linking the diffusion attenuated MR signal to the lung
      microstructure. To adapt this technique to small animals, certain modifications
      in MR protocol and data analysis are required, reflecting the smaller size of
      mouse alveoli and acinar airways. This is the subject of the present paper.
      Herein, we established empirical relationships relating diffusion measurements to
      geometrical parameters of lung acinar airways with dimensions typical for mice
      and rats by using simulations of diffusion in the airways. We have also adjusted
      the MR protocol to acquire data with much shorter diffusion times compared with
      humans to accommodate the substantially smaller acinar airway length. We apply
      this technique to study mouse lungs ex vivo. Our MR-based measurements yield mean
      values of lung surface-to-volume ratio of 670 cm(-1), alveolar density of 3,200
      per mm(3), alveolar depth of 55 MUm, and mean chord length of 62 MUm, all
      consistent with published data obtained histologically in mice by unbiased
      methods. The proposed technique can be used for in vivo experiments, opening a
      door for longitudinal studies of lung morphometry in mice and other small
      animals.

PMID- 20798271
TI  - Fatty diabetic lung: functional impairment in a model of metabolic syndrome.
AB  - The Zucker diabetic fatty (ZDF fa/fa) rat with genetic leptin insensitivity
      develops obesity and Type 2 diabetes mellitus (T2DM) with age accompanied by
      hyperplastic changes in the distal lung (Am J Physiol Lung Cell Mol Physiol 298:
      L392-L403, 2010). To determine the functional consequences of structural changes,
      we developed a rebreathing (RB) technique to simultaneously measure lung volume,
      pulmonary blood flow, lung diffusing capacity (Dl(CO)), membrane diffusing
      capacity (Dm(CO)), pulmonary capillary blood volume (Vc), and septal tissue
      volume in anesthetized tracheostomized male ZDF fa/fa and matched lean (+/+)
      control animals at 4, 8, and 12 mo of age. Results obtained by RB technique were
      compared with that measured by a single-breath (SB) technique and to that
      expected in a wide range of species. In fa/fa animals compared with +/+, lung
      volumes and compliance were 13-35% lower at different ages, and the normal age
      related increase in lung compliance was no longer evident. Mean pulmonary blood
      flow declined with age in fa/fa but not in +/+ animals. Dl(CO) measured at a
      given pulmonary blood flow was 20-43% lower at different ages due to reductions
      in both Dm(CO) and Vc. Septal tissue volume was also reduced in older fa/fa rats.
      We conclude that obese rats with T2DM develop significant restrictive pulmonary
      defects with diffusion impairment in a pattern similar to that previously
      reported in obese human subjects with T2DM. Functional impairment became
      exaggerated with age and duration of T2DM. In both fa/fa and +/+ animals, Dl(CO)
      measured by RB was systematically higher than by SB technique whereas lung volume
      was similar, a finding consistent with heterogeneous distribution of ventilation
      in the rat lung.

PMID- 20798273
TI  - P2X2/3 and P2X3 receptors contribute to the metaboreceptor component of the
      exercise pressor reflex.
AB  - The exercise pressor reflex is due to activation of thin fiber afferents within
      contracting muscle. These afferents are in part stimulated by ATP activation of
      purinergic 2X (P2X) receptors during contraction. Which of the P2X receptors
      contribute to the reflex is unknown; however, P2X2/3 and P2X3 receptor subtypes
      are good candidates because they are located on thin fiber afferents and are
      involved in sensory neurotransmission. To determine if P2X2/3 and P2X3 receptors
      evoke the metabolic component of the exercise pressor reflex, we examined the
      effect of two P2X2/3 and P2X3 antagonists, A-317491 (10 mg/kg) and RO-3 (10
      mg/kg), on the pressor response to injections of alpha,beta-methylene ATP
      (alpha,beta-MeATP; 50 MUg/kg), freely perfused static contraction, contraction of
      the triceps surae muscles while the circulation was occluded, and postcontraction
      circulatory occlusion in decerebrate cats. We found that the antagonists reduced
      the pressor response to alpha,beta-MeATP injection (before Delta 20 +/- 3 mmHg;
      drug Delta 11 +/- 3 mmHg; P < 0.05), suggesting the antagonists were effective in
      blocking P2X2/3 and P2X3 receptors. P2X2/3 and P2X3 receptor blockade reduced the
      pressor response to freely perfused contraction (before Delta 33 +/- 5 mmHg; drug
      Delta 15 +/- 5 mmHg; P < 0.05), contraction with the circulation occluded (before
      Delta 52 +/- 7 mmHg; drug Delta 20 +/- 4 mmHg; P < 0.05), and during
      postcontraction circulatory occlusion (before Delta 15 +/- 1 mmHg; drug Delta 5
      +/- 1 mmHg; P < 0.05). Our findings suggest that P2X2/3 and P2X3 receptors
      contribute to the metabolic component of the exercise pressor reflex in
      decerebrate cats.

PMID- 20798275
TI  - Contributions of visible and ultraviolet parts of sunlight to photoinhibition.
AB  - Photoinhibition is light-induced inactivation of PSII, and action spectrum
      measurements have shown that UV light causes photoinhibition much more
      efficiently than visible light. In the present study, we quantified the
      contribution of the UV part of sunlight in photoinhibition of PSII in leaves.
      Greenhouse-grown pumpkin leaves were pretreated with lincomycin to block the
      repair of photoinhibited PSII, and exposed to sunlight behind a UV-permeable or
      UV-blocking filter. Oxygen evolution and Chl fluorescence measurements showed
      that photoinhibition proceeds 35% more slowly under the UV-blocking than under
      the UV-permeable filter. Experiments with a filter that blocks UV-B but transmits
      UV-A and visible light revealed that UV-A light is almost fully responsible for
      the UV effect. The difference between leaves illuminated through a UV-blocking
      and UV-transparent filter disappeared when leaves of field-grown pumpkin plants
      were used. Thylakoids isolated from field-grown and greenhouse-grown plants were
      equally sensitive to UV light, and measurements of UV-induced fluorescence from
      leaves indicated that the protection of the field-grown plants was caused by
      substances that block the passage of UV light to the chloroplasts. Thus, the UV
      part of sunlight, especially the UV-A part, is potentially highly important in
      photoinhibition of PSII but the UV-screening compounds of plant leaves may offer
      almost complete protection against UV-induced photoinhibition.

PMID- 20798274
TI  - Forty-eight hours of unloading and 24 h of reloading lead to changes in global
      gene expression patterns related to ubiquitination and oxidative stress in
      humans.
AB  - Although short-term disuse does not result in measurable muscle atrophy, studies
      suggest that molecular changes associated with protein degradation may be
      initiated within days of the onset of a disuse stimulus. We examined the global
      gene expression patterns in sedentary men (n = 7, mean age +/- SD = 22.1 +/- 3.7
      yr) following 48 h unloading (UL) via unilateral lower limb suspension and 24 h
      reloading (RL). Biopsy samples of the left vastus lateralis muscle were collected
      at baseline, 48 h UL, and 24 h RL. Expression changes were measured by microarray
      and gene clustering; identification of enriched functions and canonical pathways
      were performed using the Database for Annotation, Visualization and Integrated
      Discovery (DAVID) and Ingenuity Pathway Analysis (IPA). Four genes were validated
      with quantitative RT-PCR (qRT-PCR), and protein levels were measured with Western
      blot. Of the upregulated genes after UL, the most enriched functional group and
      highest ranked canonical pathway were related to protein ubiquitination. The
      oxidative stress response pathway was the second highest ranked canonical
      pathway. Of the downregulated genes, functions related to mitochondrial
      metabolism were the most highly enriched. In general, gene expression patterns
      following UL persisted following RL. qRT-PCR confirmed increases in mRNA for
      ubiquitin proteasome pathway-related E3 ligase Atrogin1 (but not accompanying
      increases in protein products) and stress response gene heme oxygenase-1 (HMOX,
      which showed a trend toward increases in protein products at 48 h UL) as well as
      extracellular matrix (ECM) component COL4A3. The gene expression patterns were
      not reversed on RL, suggesting that molecular responses to short-term periods of
      skeletal muscle inactivity may persist after activity resumes.

PMID- 20798276
TI  - Identification and testing of superior reference genes for a starting pool of
      transcript normalization in Arabidopsis.
AB  - Genes that are stably expressed during development or in response to
      environmental changes are essential for accurate normalization in qRT-PCR
      experiments. To prevent possible misinterpretation caused by the use of unstable
      housekeeping genes, such as UBQ10, ACT, TUB and EF-1alpha, as a reference, the
      use of 20 stably expressed genes identified from microarray analyses was
      proposed. Furthermore, it was recommended that at least four genes among them be
      tested to identify suitable reference genes under different experimental
      conditions. However, testing the 20 potential reference genes under any condition
      is inefficient. Furthermore, since their stability still varies, there is a need
      to identify a subset of genes that are more stable than others, which can be used
      as a starting pool for testing. Here, we validated the expression stability of
      the potential candidate genes together with the above-mentioned conventional
      reference genes under six experimental conditions commonly used in plant
      developmental biology. To increase fidelity, three independent validation
      experiments were carried out for each experimental condition. A hypothetical
      normalization factor, which is the geometric mean of genes that were identified
      as stably expressed genes in each experiment, was used to exclude unstable genes
      under a given condition. We identified a subset of genes showing higher
      expression stability under specific experimental conditions. We recommend the use
      of these genes as a starting pool for the identification of suitable reference
      genes under given experimental conditions to ensure accurate normalization in qRT
      PCR analysis.

PMID- 20798278
TI  - Application of the Seattle Heart Failure Model in ambulatory patients presented
      to an advanced heart failure therapeutics committee.
AB  - BACKGROUND: We sought to assess the predictive value of the Seattle Heart Failure
      Model (SHFM) when applied to ambulatory patients with advanced heart failure (HF)
      presented to an advanced HF therapeutics committee at a tertiary care US
      institution. METHODS AND RESULTS: We evaluated model discrimination and
      calibration in 215 consecutive ambulatory patients who were presented to the
      Cleveland Clinic advanced HF therapeutics committee between 2004 to 2007 for
      evaluation for advanced options including transplantation and ventricular assist
      device (VAD). Analyses were stratified by committee decision (not listed versus
      listed United Network of Organ Sharing [UNOS] Status 2). Eighty-five percent had
      1 or no missing SHFM variables. The primary outcome was a composite of all-cause
      mortality, VAD, or urgent (UNOS Status 1) transplantation. During a median follow
      up of 24 months, 68 died, 18 received VAD support, and 81 underwent heart
      transplantation. Discrimination was modest both for those not listed (c-index,
      0.683 at 1 year and 0.648 at 2 years), and for those listed UNOS status 2 (c
      index, 0.629 at 1 year and 0.628 at 2 years). Calibration was acceptable among
      those patients not listed for heart transplantation but with substantial
      underestimation of risk (ie, overestimation of survival free of VAD or urgent
      transplantation) among UNOS status 2 patients. CONCLUSIONS: In ambulatory
      patients presented to an advanced HF therapeutics committee for evaluation for
      heart transplantation, the SHFM offers modest discrimination of risk for the
      primary composite outcome of mortality, VAD, or urgent transplantation, with
      underestimation of risk in those patients listed for nonurgent transplantation.
      Interpretation of risk prediction by the SHFM in this patient population must be
      done with caution.

PMID- 20798277
TI  - Predictors of incident heart failure in a large insured population: a one million
      person-year follow-up study.
AB  - BACKGROUND: Studies on the incidence and predictors of heart failure (HF) are
      often restricted to elderly persons or identify only inpatient cases. METHODS AND
      RESULTS: We determined the incidence and predictors of new HF diagnosed in either
      outpatient or inpatient settings, among 359 947 women and men (age >=18 years)
      insured by Kaiser Permanente Georgia at any time during calendar years 2000 to
      2005. Subjects were free of HF at baseline, and incident HF was identified with
      ICD-9 codes (1 inpatient or 2 outpatient HF visits). We developed multivariable
      Cox models to assess the association of antecedent factors (coronary heart
      disease, hypertension, diabetes mellitus, atrial fibrillation, and valvular heart
      disease) with incident HF. Separate models were created for each sex and for
      newly diagnosed HF in outpatient or inpatient settings. There were 4001 incident
      HF cases (50% women and 48% in subjects <65 years old), during 1 015 794 person
      years of follow-up. The incidence rate of HF was greater in men than in women
      (4.24 versus 3.68 per 1000 person-years) but was stable across the study interval
      in both sexes. Two thirds of incident HF cases from this population occurred in
      outpatients. These 5 antecedent factors and age yielded excellent discrimination
      for incident HF in both outpatients and inpatients and in both sexes (C >0.85 in
      all models). CONCLUSIONS: Common modifiable risk factors accurately discriminate
      women and men at risk for HF diagnosed in either outpatient or inpatient
      settings. Approximately two thirds of new HF cases in our insured population were
      diagnosed in outpatients; more research is needed to characterize these subjects
      and their prognosis.

PMID- 20798279
TI  - The effects of single nucleotide polymorphisms in CYP2A13 on metabolism of 5
      methoxypsoralen.
AB  - A number of studies have demonstrated that cytochrome P450 (P450) converts
      furanocoumarin derivatives into reactive molecules, which form covalent bonds to
      biomolecules. 5-Methoxypsoralen (5-MOP) is a natural furanocoumarin from
      apiaceous plants. In this study, we examined the effect on 5-MOP metabolism of
      single nucleotide polymorphisms (SNPs) in CYP2A13. We used Escherichia coli
      generated recombinant enzymes of wild-type CYP2A13*1 and five variants, CYP2A13*4
      (R101Q), CYP2A13*5 (F453Y), CYP2A13*6 (R494C), CYP2A13*8 (D158E), and CYP2A13*9
      (V323L). In high-performance liquid chromatography analyses of 5-MOP metabolic
      products, CYP2A13*1 converted 5-MOP into 5-MOP dihydrodiol; K(m) and V(max)
      values of the reaction were 1.44 +/- 0.17 MUM and 4.23 +/- 0.36 nmol/(min . nmol
      P450), respectively. The generation of a dihydrodiol from 5-MOP implies that
      conversion by CYP2A13 causes toxicity due to the formation of covalent bonds with
      DNA or proteins. Most of the CYP2A13 variants could metabolize 5-MOP; K(m) values
      for CYP2A13*5, *6, *8, and *9 were 1.63 +/- 0.12, 1.36 +/- 0.10, 0.85 +/- 0.09,
      and 0.58 +/- 0.06 MUM, respectively, and V(max) values were 3.20 +/- 0.13, 4.69
      +/- 0.13, 2.34 +/- 0.07, and 1.84 +/- 0.09 nmol/(min . nmol P450), respectively.
      However, the processing of 5-MOP by CYP2A13*4 was not detectable. Based on this
      data, we hypothesize that SNPs within the CYP2A13 gene affect metabolism of 5-MOP
      in humans.

PMID- 20798280
TI  - Mitotic recombination in patients with ichthyosis causes reversion of dominant
      mutations in KRT10.
AB  - Somatic loss of wild-type alleles can produce disease traits such as neoplasia.
      Conversely, somatic loss of disease-causing mutations can revert phenotypes;
      however, these events are infrequently observed. Here we show that ichthyosis
      with confetti, a severe, sporadic skin disease in humans, is associated with
      thousands of revertant clones of normal skin that arise from loss of
      heterozygosity on chromosome 17q via mitotic recombination. This allowed us to
      map and identify disease-causing mutations in the gene encoding keratin 10
      (KRT10); all result in frameshifts into the same alternative reading frame,
      producing an arginine-rich C-terminal peptide that redirects keratin 10 from the
      cytokeratin filament network to the nucleolus. The high frequency of somatic
      reversion in ichthyosis with confetti suggests that revertant stem cell clones
      are under strong positive selection and/or that the rate of mitotic recombination
      is elevated in individuals with this disorder.

PMID- 20798281
TI  - Freezing tolerance in plants requires lipid remodeling at the outer chloroplast
      membrane.
AB  - Plants show complex adaptations to freezing that prevent cell damage caused by
      cellular dehydration. Lipid remodeling of cell membranes during dehydration is
      one critical mechanism countering loss of membrane integrity and cell death.
      SENSITIVE TO FREEZING 2 (SFR2), a gene essential for freezing tolerance in
      Arabidopsis, encodes a galactolipid remodeling enzyme of the outer chloroplast
      envelope membrane. SFR2 processively transfers galactosyl residues from the
      abundant monogalactolipid to different galactolipid acceptors, forming
      oligogalactolipids and diacylglycerol, which is further converted to
      triacylglycerol. The combined activity of SFR2 and triacylglycerol-biosynthetic
      enzymes leads to the removal of monogalactolipids from the envelope membrane,
      changing the ratio of bilayer- to non-bilayer-forming membrane lipids. This SFR2
      based mechanism compensates for changes in organelle volume and stabilizes
      membranes during freezing.

PMID- 20798282
TI  - Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro.
AB  - Presynaptic nerve terminals release neurotransmitters repeatedly, often at high
      frequency, and in relative isolation from neuronal cell bodies. Repeated release
      requires cycles of soluble N-ethylmaleimide-sensitive factor attachment protein
      receptor (SNARE)-complex assembly and disassembly, with continuous generation of
      reactive SNARE-protein intermediates. Although many forms of neurodegeneration
      initiate presynaptically, only few pathogenic mechanisms are known, and the
      functions of presynaptic proteins linked to neurodegeneration, such as alpha
      synuclein, remain unclear. Here, we show that maintenance of continuous
      presynaptic SNARE-complex assembly required a nonclassical chaperone activity
      mediated by synucleins. Specifically, alpha-synuclein directly bound to the SNARE
      protein synaptobrevin-2/vesicle-associated membrane protein 2 (VAMP2) and
      promoted SNARE-complex assembly. Moreover, triple-knockout mice lacking
      synucleins developed age-dependent neurological impairments, exhibited decreased
      SNARE-complex assembly, and died prematurely. Thus, synucleins may function to
      sustain normal SNARE-complex assembly in a presynaptic terminal during aging.

PMID- 20798283
TI  - Kepler-9: a system of multiple planets transiting a Sun-like star, confirmed by
      timing variations.
AB  - The Kepler spacecraft is monitoring more than 150,000 stars for evidence of
      planets transiting those stars. We report the detection of two Saturn-size
      planets that transit the same Sun-like star, based on 7 months of Kepler
      observations. Their 19.2- and 38.9-day periods are presently increasing and
      decreasing at respective average rates of 4 and 39 minutes per orbit; in
      addition, the transit times of the inner body display an alternating variation of
      smaller amplitude. These signatures are characteristic of gravitational
      interaction of two planets near a 2:1 orbital resonance. Six radial-velocity
      observations show that these two planets are the most massive objects orbiting
      close to the star and substantially improve the estimates of their masses. After
      removing the signal of the two confirmed giant planets, we identified an
      additional transiting super-Earth-size planet candidate with a period of 1.6
      days.

PMID- 20798284
TI  - What is STEM education?

PMID- 20798285
TI  - Chronic fatigue syndrome. New XMRV paper looks good, skeptics admit--yet doubts
      linger.

PMID- 20798287
TI  - China. Astronomers hope their prize telescope isn't blinded by the light.

PMID- 20798286
TI  - Marine ecology. Hard summer for corals kindles fears for survival of reefs.

PMID- 20798288
TI  - Research facilities. U.S. physicists eye Australia for new site of gravitational
      wave detector.

PMID- 20798289
TI  - Cell biology. To scientists' dismay, mixed-up cell lines strike again.

PMID- 20798291
TI  - U.S. science policy. NSF turns math earmark on its ear to fund new institute.

PMID- 20798292
TI  - Chemistry. Organizers panned for omitting Israelis from meeting in Jordan.

PMID- 20798294
TI  - Archaeology. Google Earth shows clandestine worlds.

PMID- 20798295
TI  - Infectious disease. From pigs to people: the emergence of a new superbug.

PMID- 20798296
TI  - Dietary restriction: standing up for sirtuins.

PMID- 20798300
TI  - Dietary restriction: theory fails to satiate.

PMID- 20798297
TI  - Comment on "A southern tyrant reptile".
AB  - Benson et al. (Brevia, 26 March 2010, p. 1613) reported on an Australian
      tyrannosauroid, represented by a pubis from the late Early Cretaceous of
      Victoria. However, our examination of this specimen reveals that the critical
      character used for this referral is not present. We contend that the bone likely
      belongs to a currently recognized group of Australian theropod or another group
      not currently known.

PMID- 20798302
TI  - Disasters. Scenario-building for the Deepwater Horizon oil spill.

PMID- 20798303
TI  - Geophysics. Fine-scale modeling of global plate tectonics.

PMID- 20798304
TI  - Immunology. Prime, boost, and broaden.

PMID- 20798305
TI  - Behavior. Decisions made better.

PMID- 20798306
TI  - Developmental biology. Microenvironment mimicry.

PMID- 20798307
TI  - Chemistry. Opening the door to peptide-based porous solids.

PMID- 20798308
TI  - Virology. Looking inside adenovirus.

PMID- 20798309
TI  - SPORE series winner. The universe online.

PMID- 20798310
TI  - CoRoT reveals a magnetic activity cycle in a Sun-like star.
AB  - The 11-year activity cycle of the Sun is a consequence of a dynamo process
      occurring beneath its surface. We analyzed photometric data obtained by the CoRoT
      space mission, showing solarlike oscillations in the star HD49933, for signatures
      of stellar magnetic activity. Asteroseismic measurements of global changes in the
      oscillation frequencies and mode amplitudes reveal a modulation of at least 120
      days, with the minimum frequency shift corresponding to maximum amplitude as in
      the Sun. These observations are evidence of a stellar magnetic activity cycle
      taking place beneath the surface of HD49933 and provide constraints for stellar
      dynamo models under conditions different from those of the Sun.

PMID- 20798311
TI  - The dynamics of plate tectonics and mantle flow: from local to global scales.
AB  - Plate tectonics is regulated by driving and resisting forces concentrated at
      plate boundaries, but observationally constrained high-resolution models of
      global mantle flow remain a computational challenge. We capitalized on advances
      in adaptive mesh refinement algorithms on parallel computers to simulate global
      mantle flow by incorporating plate motions, with individual plate margins
      resolved down to a scale of 1 kilometer. Back-arc extension and slab rollback are
      emergent consequences of slab descent in the upper mantle. Cold thermal anomalies
      within the lower mantle couple into oceanic plates through narrow high-viscosity
      slabs, altering the velocity of oceanic plates. Viscous dissipation within the
      bending lithosphere at trenches amounts to approximately 5 to 20% of the total
      dissipation through the entire lithosphere and mantle.

PMID- 20798312
TI  - Atomic structure of human adenovirus by cryo-EM reveals interactions among
      protein networks.
AB  - Construction of a complex virus may involve a hierarchy of assembly elements.
      Here, we report the structure of the whole human adenovirus virion at 3.6
      angstroms resolution by cryo-electron microscopy (cryo-EM), revealing in situ
      atomic models of three minor capsid proteins (IIIa, VIII, and IX), extensions of
      the (penton base and hexon) major capsid proteins, and interactions within three
      protein-protein networks. One network is mediated by protein IIIa at the
      vertices, within group-of-six (GOS) tiles--a penton base and its five surrounding
      hexons. Another is mediated by ropes (protein IX) that lash hexons together to
      form group-of-nine (GON) tiles and bind GONs to GONs. The third, mediated by IIIa
      and VIII, binds each GOS to five surrounding GONs. Optimization of adenovirus for
      cancer and gene therapy could target these networks.

PMID- 20798313
TI  - Dynamical instability produces transform faults at mid-ocean ridges.
AB  - Transform faults at mid-ocean ridges--one of the most striking, yet enigmatic
      features of terrestrial plate tectonics--are considered to be the inherited
      product of preexisting fault structures. Ridge offsets along these faults
      therefore should remain constant with time. Here, numerical models suggest that
      transform faults are actively developing and result from dynamical instability of
      constructive plate boundaries, irrespective of previous structure. Boundary
      instability from asymmetric plate growth can spontaneously start in alternate
      directions along successive ridge sections; the resultant curved ridges become
      transform faults within a few million years. Fracture-related rheological
      weakening stabilizes ridge-parallel detachment faults. Offsets along the
      transform faults change continuously with time by asymmetric plate growth and
      discontinuously by ridge jumps.

PMID- 20798314
TI  - An adaptable peptide-based porous material.
AB  - Porous materials find widespread application in storage, separation, and
      catalytic technologies. We report a crystalline porous solid with adaptable
      porosity, in which a simple dipeptide linker is arranged in a regular array by
      coordination to metal centers. Experiments reinforced by molecular dynamics
      simulations showed that low-energy torsions and displacements of the peptides
      enabled the available pore volume to evolve smoothly from zero as the guest
      loading increased. The observed cooperative feedback in sorption isotherms
      resembled the response of proteins undergoing conformational selection,
      suggesting an energy landscape similar to that required for protein folding. The
      flexible peptide linker was shown to play the pivotal role in changing the pore
      conformation.

PMID- 20798315
TI  - Trapping a diradical transition state by mechanochemical polymer extension.
AB  - Transition state structures are central to the rates and outcomes of chemical
      reactions, but their fleeting existence often leaves their properties to be
      inferred rather than observed. By treating polybutadiene with a difluorocarbene
      source, we embedded gem-difluorocyclopropanes (gDFCs) along the polymer backbone.
      We report that mechanochemical activation of the polymer under tension opens the
      gDFCs and traps a 1,3-diradical that is formally a transition state in their
      stress-free electrocyclic isomerization. The trapped diradical lives long enough
      that we can observe its noncanonical participation in bimolecular addition
      reactions. Furthermore, the application of a transient tensile force induces a
      net isomerization of the trans-gDFC into its less-stable cis isomer, leading to
      the counterintuitive result that the gDFC contracts in response to a transient
      force of extension.

PMID- 20798316
TI  - Secreted peptide signals required for maintenance of root stem cell niche in
      Arabidopsis.
AB  - Stem cells are maintained in the niche by intercellular interactions and
      signaling networks. In this work, we study extracellular signals required for
      maintenance of the root stem cell niche in higher plants. We identify a family of
      functionally redundant homologous peptides that are secreted, tyrosine-sulfated,
      and expressed mainly in the stem cell area and the innermost layer of central
      columella cells. We name these peptides root meristem growth factors (RGFs). RGFs
      are required for maintenance of the root stem cell niche and transit amplifying
      cell proliferation in Arabidopsis. RGF1 defines expression levels and patterns of
      the stem cell transcription factor PLETHORA, mainly at the posttranscriptional
      level. The RGFs function independently of the auxin pathway. These peptide
      signals play a crucial role in postembryonic root development.

PMID- 20798317
TI  - Genomic comparison of the ants Camponotus floridanus and Harpegnathos saltator.
AB  - The organized societies of ants include short-lived worker castes displaying
      specialized behavior and morphology and long-lived queens dedicated to
      reproduction. We sequenced and compared the genomes of two socially divergent ant
      species: Camponotus floridanus and Harpegnathos saltator. Both genomes contained
      high amounts of CpG, despite the presence of DNA methylation, which in non
      Hymenoptera correlates with CpG depletion. Comparison of gene expression in
      different castes identified up-regulation of telomerase and sirtuin deacetylases
      in longer-lived H. saltator reproductives, caste-specific expression of microRNAs
      and SMYD histone methyltransferases, and differential regulation of genes
      implicated in neuronal function and chemical communication. Our findings provide
      clues on the molecular differences between castes in these two ants and establish
      a new experimental model to study epigenetics in aging and behavior.

PMID- 20798318
TI  - Crystal structure of human adenovirus at 3.5 A resolution.
AB  - Rational development of adenovirus vectors for therapeutic gene transfer is
      hampered by the lack of accurate structural information. Here, we report the x
      ray structure at 3.5 angstrom resolution of the 150-megadalton adenovirus capsid
      containing nearly 1 million amino acids. We describe interactions between the
      major capsid protein (hexon) and several accessory molecules that stabilize the
      capsid. The virus structure also reveals an altered association between the
      penton base and the trimeric fiber protein, perhaps reflecting an early event in
      cell entry. The high-resolution structure provides a substantial advance toward
      understanding the assembly and cell entry mechanisms of a large double-stranded
      DNA virus and provides new opportunities for improving adenovirus-mediated gene
      transfer.

PMID- 20798319
TI  - Insects betray themselves in nature to predators by rapid isomerization of green
      leaf volatiles.
AB  - Plants emit green leaf volatiles (GLVs) in response to herbivore damage, thereby
      attracting predators of the herbivores as part of an indirect defense. The GLV
      component of this indirect defense was thought to be a general wound signal
      lacking herbivore-specific information. We found that Manduca sexta-infested
      Nicotiana attenuata attract the generalist hemipteran predator Geocoris spp. as
      the result of an herbivore-induced decrease in the (Z)/(E) ratio of released
      GLVs, and that these changes in the volatile bouquet triple the foraging
      efficiency of predators in nature. These (E)-isomers are produced from plant
      derived (Z)-isomers but are converted by a heat-labile constituent of herbivore
      oral secretions. Hence, attacking herbivores initiate the release of an indirect
      defense a full day before the attacked plants manufacture their own defensive
      compounds.

PMID- 20798320
TI  - Optimally interacting minds.
AB  - In everyday life, many people believe that two heads are better than one. Our
      ability to solve problems together appears to be fundamental to the current
      dominance and future survival of the human species. But are two heads really
      better than one? We addressed this question in the context of a collective low
      level perceptual decision-making task. For two observers of nearly equal visual
      sensitivity, two heads were definitely better than one, provided they were given
      the opportunity to communicate freely, even in the absence of any feedback about
      decision outcomes. But for observers with very different visual sensitivities,
      two heads were actually worse than the better one. These seemingly discrepant
      patterns of group behavior can be explained by a model in which two heads are
      Bayes optimal under the assumption that individuals accurately communicate their
      level of confidence on every trial.

PMID- 20798321
TI  - Phosphatidic acid is a pH biosensor that links membrane biogenesis to metabolism.
AB  - Recognition of lipids by proteins is important for their targeting and activation
      in many signaling pathways, but the mechanisms that regulate such interactions
      are largely unknown. Here, we found that binding of proteins to the ubiquitous
      signaling lipid phosphatidic acid (PA) depended on intracellular pH and the
      protonation state of its phosphate headgroup. In yeast, a rapid decrease in
      intracellular pH in response to glucose starvation regulated binding of PA to a
      transcription factor, Opi1, that coordinately repressed phospholipid metabolic
      genes. This enabled coupling of membrane biogenesis to nutrient availability.

PMID- 20798323
TI  - A treatment for dysprosody in childhood apraxia of speech.
AB  - PURPOSE: Dysprosody is considered a core feature of childhood apraxia of speech
      (CAS), especially impaired production of lexical stress. Few studies have tested
      the effects of intervention for dysprosody. This Phase II study with 3 children
      investigated the efficacy of a treatment targeting improved control of relative
      syllable durations in 3-syllable nonwords representing strong-weak (SW) and weak
      strong (WS) stress patterns (e.g., BAtigu or baTIgu). Treatment sessions were
      structured along the principles of motor learning (PML) approach. METHOD: Three
      children, age 7 to 10 years, with mild to moderate CAS and normal language
      development participated in an intensive 3-week treatment. Within-participant
      designs with multiple baselines across participants and behaviors were used to
      examine acquisition, generalization, and maintenance of skill. RESULTS: All
      children improved in their ability to control relative duration of syllables in
      SW and WS nonwords. Improvement was also noted in control of loudness and pitch
      contrasts. Treatment effects generalized to untreated nonword stimuli, but
      minimal change was seen in production of real words. CONCLUSION: Findings support
      the efficacy of this approach for improving production of lexical stress
      contrasts. Structuring the intervention according to the PML approach likely
      stimulated strong maintenance and generalization effects.

PMID- 20798324
TI  - Spoken word classification in children and adults.
AB  - PURPOSE: Preschool children often have difficulties in word classification,
      despite good speech perception and production. Some researchers suggest that they
      represent words using phonetic features rather than phonemes. In this study, the
      authors examined whether there is a progression from feature-based to phoneme
      based processing across age groups and whether responses are consistent across
      tasks and stimuli. METHOD: In Study 1, 120 three- to five-year-old children
      completed 3 tasks assessing use of phonetic features in classification, with an
      additional 58 older children completing 1 of the 3 tasks. In Study 2, all of the
      children, together with an additional adult sample, completed a nonword learning
      task. RESULTS: In all 4 tasks, children classified words sharing phonemes as
      similar. In addition, children regarded words as similar if they shared manner of
      articulation, particularly word finally. Adults also showed this sensitivity to
      manner, but across the tasks, there was a pattern of increasing use of phonemic
      information with age. CONCLUSIONS: Children tend to classify words as similar if
      they share phonemes or if they share manner of articulation word finally. Use of
      phonemic information becomes more common with age.

PMID- 20798325
TI  - Semantic abilities in children with pragmatic language impairment: the case of
      picture naming skills.
AB  - PURPOSE: The semantic abilities of children with pragmatic language impairment
      (PLI) are subject to debate. The authors investigated picture naming and
      definition skills in 5-year-olds with PLI in comparison to typically developing
      children. METHOD: 84 children with PLI and 80 age-matched typically developing
      children completed receptive vocabulary, picture naming, and definition tasks.
      RESULTS: The PLI group scored lower on the receptive vocabulary and picture
      naming tasks. Word length and frequency affected naming accuracy in both groups.
      Children with PLI showed higher numbers of semantic errors, nonrelated errors,
      and omissions and circumlocutions. The error-type distribution differed between
      groups: PLI children showed disproportionate levels of nonrelated errors. In the
      definition task, PLI children showed lower information accuracy for accurately
      named pictures and comparable accuracy for incorrectly named pictures.
      Qualitative analysis suggested a high incidence of pragmatically inappropriate
      definitions for the PLI group. Naming accuracy for both groups improved equally
      after giving semantic cues. CONCLUSIONS: These findings suggest a deficit in
      object identification and/or naming selection. It might be premature to conclude
      that children with PLI show normal semantic abilities. The results are largely
      consistent with a general language delay; however, there is also some evidence of
      a qualitative difference between both groups.

PMID- 20798326
TI  - Spoken word recognition in school-age children with SLI: semantic, phonological,
      and repetition priming.
AB  - PURPOSE: The purpose of this study was to contribute to the current understanding
      of how children with specific language impairment (SLI) organize their mental
      lexicons. The study examined semantic and phonological priming in children with
      and without SLI. METHOD: Thirteen children (7;0-11;3 [years;months]) with SLI and
      13 age-matched children with typical language development participated in this
      study. Prime-target pairs (semantic, phonological, and repetition) were embedded
      within a running list of words so that the actual pairs were imperceptible.
      Reaction times to an animacy judgment (alive vs. not alive) were analyzed. The
      experiment featured 500-ms and 1,000-ms interstimulus intervals (ISIs) between
      primes and targets. RESULTS: Children with SLI exhibited priming effects in the
      repetition condition at both ISIs; however, phonological and semantic effects
      were absent. Typically developing children exhibited effects in the repetition at
      both ISIs. Semantic and phonological effects were absent at 500 ms ISIs, but
      present at 1,000 ms ISIs. CONCLUSIONS: Although children with SLI have priming
      mechanisms similar to those of their age-matched peers, the absence of semantic
      and phonological priming suggests that these connections are not strong enough by
      themselves to yield priming effects. These findings are discussed in the context
      of semantic and phonological priming, representation, and generalized slowing.

PMID- 20798327
TI  - Phosphoenolpyruvate provision to plastids is essential for gametophyte and
      sporophyte development in Arabidopsis thaliana.
AB  - Restriction of phosphoenolpyruvate (PEP) supply to plastids causes lethality of
      female and male gametophytes in Arabidopsis thaliana defective in both a
      phosphoenolpyruvate/phosphate translocator (PPT) of the inner envelope membrane
      and the plastid-localized enolase (ENO1) involved in glycolytic PEP provision.
      Homozygous double mutants of cue1 (defective in PPT1) and eno1 could not be
      obtained, and homozygous cue1 heterozygous eno1 mutants [cue1/eno1(+/-)]
      exhibited retarded vegetative growth, disturbed flower development, and up to 80%
      seed abortion. The phenotypes of diminished oil in seeds, reduced flavonoids and
      aromatic amino acids in flowers, compromised lignin biosynthesis in stems, and
      aberrant exine formation in pollen indicate that cue1/eno1(+/-) disrupts multiple
      pathways. While diminished fatty acid biosynthesis from PEP via plastidial
      pyruvate kinase appears to affect seed abortion, a restriction in the shikimate
      pathway affects formation of sporopollonin in the tapetum and lignin in the stem.
      Vegetative parts of cue1/eno1(+/-) contained increased free amino acids and
      jasmonic acid but had normal wax biosynthesis. ENO1 overexpression in cue1
      rescued the leaf and root phenotypes, restored photosynthetic capacity, and
      improved seed yield and oil contents. In chloroplasts, ENO1 might be the only
      enzyme missing for a complete plastidic glycolysis.

PMID- 20798328
TI  - Tobacco GTBP1, a homolog of human heterogeneous nuclear ribonucleoprotein,
      protects telomeres from aberrant homologous recombination.
AB  - Telomeres are nucleoprotein complexes essential for the integrity of eukaryotic
      chromosomes. Cellular roles of single-stranded telomeric DNA binding proteins
      have been extensively described in yeast and animals, but our knowledge about
      plant single-strand telomeric factors is rudimentary. Here, we investigated
      Nicotiana tabacum G-strand-specific single-stranded telomere binding proteins
      (GTBPs), homologs of a human heterogeneous nuclear ribonucleoprotein. GTBPs bound
      specifically to the plant single-stranded (TTTAGGG)(4) telomeric repeat element
      in vitro and were associated with telomeric sequences in tobacco BY-2 suspension
      cells. Transgenic plants (35S:RNAi-GTBP1), in which GTBP1 was suppressed,
      exhibited severe developmental anomalies. In addition, the chromosomes of
      35S:RNAi-GTBP1 cells displayed elongated telomeres, frequent formation of
      extrachromosomal telomeric circles, and numerous abnormal anaphase bridges,
      indicating that GTBP1 knockdown tobacco plants experienced genome instability.
      GTBP1 inhibited strand invasion, an initial step in interchromosomal homologous
      recombination. We propose that GTBP1 plays a critical role in telomere structure
      and function by preventing aberrant interchromosomal telomeric homologous
      recombination in tobacco.

PMID- 20798329
TI  - Perturbation of indole-3-butyric acid homeostasis by the UDP-glucosyltransferase
      UGT74E2 modulates Arabidopsis architecture and water stress tolerance.
AB  - Reactive oxygen species and redox signaling undergo synergistic and antagonistic
      interactions with phytohormones to regulate protective responses of plants
      against biotic and abiotic stresses. However, molecular insight into the nature
      of this crosstalk remains scarce. We demonstrate that the hydrogen peroxide
      responsive UDP-glucosyltransferase UGT74E2 of Arabidopsis thaliana is involved in
      the modulation of plant architecture and water stress response through its
      activity toward the auxin indole-3-butyric acid (IBA). Biochemical
      characterization of recombinant UGT74E2 demonstrated that it strongly favors IBA
      as a substrate. Assessment of indole-3-acetic acid (IAA), IBA, and their
      conjugates in transgenic plants ectopically expressing UGT74E2 indicated that the
      catalytic specificity was maintained in planta. In these transgenic plants, not
      only were IBA-Glc concentrations increased, but also free IBA levels were
      elevated and the conjugated IAA pattern was modified. This perturbed IBA and IAA
      homeostasis was associated with architectural changes, including increased shoot
      branching and altered rosette shape, and resulted in significantly improved
      survival during drought and salt stress treatments. Hence, our results reveal
      that IBA and IBA-Glc are important regulators of morphological and physiological
      stress adaptation mechanisms and provide molecular evidence for the interplay
      between hydrogen peroxide and auxin homeostasis through the action of an IBA UGT.

PMID- 20798330
TI  - The conserved RNA trafficking proteins HPR1 and TEX1 are involved in the
      production of endogenous and exogenous small interfering RNA in Arabidopsis.
AB  - We previously identified Arabidopsis thaliana mutants defective in sense
      transgene posttranscriptional gene silencing (S-PTGS) that defined six loci;
      here, we describe mutants that define nine additional loci, including HYPER
      RECOMBINATION1 (HPR1), SILENCING DEFECTIVE3 (SDE3), and SDE5. Our analyses extend
      previous findings by showing that the requirement for the putative RNA helicase
      SDE3 is inversely proportional to the strength of the PTGS inducer and that the
      putative RNA trafficking protein SDE5 is an essential component of the trans
      acting small interfering RNA (tasiRNA) pathway and is required for S-PTGS but not
      inverted repeat transgene-mediated PTGS (IR-PTGS). Our screen also identified
      HPR1 as a PTGS actor. We show that hpr1 mutations negatively impact S-PTGS, IR
      PTGS, and tasiRNA pathways, resulting in increased accumulation of siRNA
      precursors and decreased accumulation of mature siRNA. In animals, HPR1/THO1 is a
      member of the conserved RNA trafficking THO/TREX complex, which also includes
      TEX1/THO3. We show that tex1 mutants, like hpr1 mutants, impact TAS precursor and
      mature tasiRNA levels, suggesting that a THO/TREX complex exists in plants and
      that this complex is important for the integrity of the tasiRNA pathway. We
      propose that both HPR1 and TEX1 participate in the trafficking of siRNA
      precursors to the ARGONAUTE catalytic center.

PMID- 20798331
TI  - Glucose-based peritoneal dialysis solution suppresses adiponectin synthesis
      through oxidative stress in an experimental model of peritoneal dialysis.
AB  - OBJECTIVE: Accumulation of visceral fat is one of the major risk factors for the
      development of cardiovascular disease in peritoneal dialysis (PD) patients.
      Adiponectin, an adipokine commonly regarded as a negative indicator of metabolic
      disease, is reported to be downregulated in its gene level in end-stage renal
      disease patients. Since excessive fat deposit is involved in increased reactive
      oxygen species (ROS), PD solution (PDS) may contribute to ROS production,
      resulting in dysregulation of adiponectin. In this study, we tested our
      hypothesis that oxidative stress induced by PDS may play a role in the regulation
      of adiponectin. METHODS: Commercial PDS containing 3.86% glucose (20 - 30 mL) was
      administered to SD rats for 12 weeks with and without N-acetylcysteine (NAC; 10
      mmol/L). ELISA was used to quantify adiponectin in plasma and spent dialysate.
      For in vitro studies, fully differentiated 3T3-L1 adipocytes and adipocytes
      isolated from abdominal fat were treated with a high glucose solution, PDS, and
      H(2)O(2). Adiponectin levels in the conditioned media were measured by ELISA and
      immunoblot assays. The mRNA levels of adiponectin in mature adipocytes were
      examined using real-time RT-PCR. RESULTS: The levels of adiponectin in plasma and
      spent dialysate were significantly downregulated by PDS and this effect was
      suppressed by NAC. In 3T3-L1 adipocytes, adiponectin secretion was inhibited by
      50 mmol/L glucose, PDS diluted 2-fold, and H(2)O(2) (200 MUmol/L). In addition,
      H(2)O(2) downregulated expression of adiponectin mRNA and secretion of
      adiponectin oligomer complexes. CONCLUSIONS: Our data suggest that ROS induced by
      conventional glucose-based PDS may contribute to pathophysiological changes in
      abdominal fat and downregulate adiponectin secreted from adipocytes during long
      term PD.

PMID- 20798332
TI  - Hypothalamic Angptl4/Fiaf is a novel regulator of food intake and body weight.
AB  - OBJECTIVE: The angiopoietin-like protein 4 (Angptl4)/fasting-induced adipose
      factor (Fiaf) is known as a regulator of peripheral lipid and glucose metabolism.
      In the present study, we investigated the physiological role of Angptl4 in
      central regulation of body weight homeostasis. RESEARCH DESIGN AND METHODS:
      Hypothalamic Angptl4 expression levels were measured using immunoblot assay
      during feeding manipulation or after administration of leptin, insulin, and
      nutrients. The effects of Angptl4 on food intake, body weight, and energy
      expenditure were determined following intracerebroventricular (ICV)
      administration of Angptl4 in C57BL/6 mice. Food intake, energy metabolism, and
      feeding responses to leptin, insulin, and nutrients were compared between Angptl4
      null mice and their wild littermates. Finally, the relationship of hypothalamic
      AMP-activated protein kinase (AMPK) and Angptl4 was studied. RESULTS:
      Hypothalamic Angptl4 expression levels were increased upon food intake or
      administration of leptin, insulin, and nutrients. Furthermore, central
      administration of Angptl4 suppressed food intake and body weight gain but
      enhanced energy expenditure. These effects were mediated via suppression of
      hypothalamic AMPK activities. Consistently, Angptl4-null mice displayed increased
      body weight and hypothalamic AMPK activity but reduced energy expenditure. Food
      intake following a fast was significantly greater in Angptl4-null mice, which was
      normalized by centrally administered Angptl4. Moreover, anorectic responses to
      leptin, insulin, and glucose were diminished in Angptl4-null mice. In contrast,
      Angptl4-null mice were resistant to diet-induced obesity, indicating obesity
      promoting effects of Angptl4 under the condition of fat-enriched diet.
      CONCLUSIONS: We have demonstrated that hypothalamic Angptl4 is regulated by
      physiological appetite regulators and mediates their anorexigenic effects via
      inhibition of hypothalamic AMPK activity. Therefore, Angptl4 appears to have an
      important role in central regulation of energy metabolism.

PMID- 20798333
TI  - Nuclear hormone retinoid X receptor (RXR) negatively regulates the glucose
      stimulated insulin secretion of pancreatic beta-cells.
AB  - OBJECTIVE: Retinoid X receptors (RXRs) are members of the nuclear hormone
      receptor superfamily and are thought to be key regulators in differentiation,
      cellular growth, and gene expression. Although several experiments using
      pancreatic beta-cell lines have shown that the ligands of nuclear hormone
      receptors modulate insulin secretion, it is not clear whether RXRs have any role
      in insulin secretion. RESEARCH DESIGN AND METHODS: To elucidate the function of
      RXRs in pancreatic beta-cells, we generated a double-transgenic mouse in which a
      dominant-negative form of RXRbeta was inducibly expressed in pancreatic beta
      cells using the Tet-On system. We also established a pancreatic beta-cell line
      from an insulinoma caused by the beta-cell-specific expression of simian virus 40
      T antigen in the above transgenic mouse. RESULTS: In the transgenic mouse,
      expression of the dominant-negative RXR enhanced the insulin secretion with high
      glucose stimulation. In the pancreatic beta-cell line, the suppression of RXRs
      also enhanced glucose-stimulated insulin secretion at a high glucose
      concentration, while 9-cis-retinoic acid, an RXR agonist, repressed it. High
      density oligonucleotide microarray analysis showed that expression of the
      dominant-negative RXR affected the expression levels of a number of genes, some
      of which have been implicated in the function and/or differentiation of beta
      cells. CONCLUSIONS: These results suggest that endogenous RXR negatively
      regulates the glucose-stimulated insulin secretion. Given these findings, we
      propose that the modulation of endogenous RXR in beta-cells may be a new
      therapeutic approach for improving impaired insulin secretion in type 2 diabetes.

PMID- 20798334
TI  - Diabetic retinopathy and cognitive decline in older people with type 2 diabetes:
      the Edinburgh Type 2 Diabetes Study.
AB  - OBJECTIVE: Cerebral microvascular disease associated with type 2 diabetes may
      exacerbate the effects of aging on cognitive function. A considerable homology
      exists between the retinal and cerebral microcirculations; a hypothesized
      association between diabetic retinopathy (DR) and cognitive decline was examined
      in older people with type 2 diabetes. RESEARCH DESIGN AND METHODS: In the
      population-based Edinburgh Type 2 Diabetes Study, 1,046 men and women aged 60-75
      years with type 2 diabetes underwent standard seven-field binocular digital
      retinal photography and a battery of seven cognitive function tests. A general
      cognitive ability score (g) was generated by principal components analysis. The
      Mill-Hill Vocabulary Scale was used to estimate premorbid cognitive ability. DR
      was graded using a modification of the Early Treatment of Diabetic Retinopathy
      Scale. RESULTS: After age and sex adjustment, a significant relationship was
      observed with increasing severity of DR (none, mild, and moderate to severe) for
      most cognitive measures. Participants with moderate-to-severe retinopathy had the
      worst g and the worst performances on the individual tests. There was a
      significant interaction between sex and retinopathy for g. In male subjects, the
      associations of retinopathy with g (and with tests of verbal fluency, mental
      flexibility, and processing speed but not memory and nonverbal reasoning)
      persisted (P < 0.05) when further adjusted for vocabulary (to estimate lifetime
      cognitive decline), depression, sociodemographic characteristics, cardiovascular
      risk factors, and macrovascular disease. CONCLUSIONS: DR was independently
      associated with estimated lifetime cognitive decline in older men with type 2
      diabetes, supporting the hypothesis that cerebral microvascular disease may
      contribute to their observed accelerated age-related cognitive decline. A sex
      interaction with stronger findings in men requires further confirmation.

PMID- 20798335
TI  - HLA class I and genetic susceptibility to type 1 diabetes: results from the Type
      1 Diabetes Genetics Consortium.
AB  - OBJECTIVE: We report here genotyping data and type 1 diabetes association
      analyses for HLA class I loci (A, B, and C) on 1,753 multiplex pedigrees from the
      Type 1 Diabetes Genetics Consortium (T1DGC), a large international collaborative
      study. RESEARCH DESIGN AND METHODS: Complete eight-locus HLA genotyping data were
      generated. Expected patient class I (HLA-A, -B, and -C) allele frequencies were
      calculated, based on linkage disequilibrium (LD) patterns with observed HLA class
      II DRB1-DQA1-DQB1 haplotype frequencies. Expected frequencies were compared to
      observed allele frequencies in patients. RESULTS: Significant type 1 diabetes
      associations were observed at all class I HLA loci. After accounting for LD with
      HLA class II, the most significantly type 1 diabetes-associated alleles were
      B*5701 (odds ratio 0.19; P = 4 * 10(-11)) and B*3906 (10.31; P = 4 * 10(-10)).
      Other significantly type 1 diabetes-associated alleles included A*2402, A*0201,
      B*1801, and C*0501 (predisposing) and A*1101, A*3201, A*6601, B*0702, B*4403,
      B*3502, C*1601, and C*0401 (protective). Some alleles, notably B*3906, appear to
      modulate the risk of all DRB1-DQA1-DQB1 haplotypes on which they reside,
      suggesting a class I effect that is independent of class II. Other class I type 1
      diabetes associations appear to be specific to individual class II haplotypes.
      Some apparent associations (e.g., C*1601) could be attributed to strong LD to
      another class I susceptibility locus (B*4403). CONCLUSIONS: These data indicate
      that HLA class I alleles, in addition to and independently from HLA class II
      alleles, are associated with type 1 diabetes.

PMID- 20798336
TI  - Black-white divergence in the relation of white blood cell count to metabolic
      syndrome in preadolescents, adolescents, and young adults: the Bogalusa Heart
      Study.
AB  - OBJECTIVE: To examine the association between white blood cell (WBC) count and
      metabolic syndrome (MetS) by growth periods in black versus white individuals in
      the general population. RESEARCH DESIGN AND METHODS: The study cohort consisted
      of 4,184 black and white preadolescents, adolescents, and adults. In this cohort,
      743 adults were followed for 8.1-20.8 years longitudinally. RESULTS: White versus
      black subjects had a significantly higher WBC count in all age-groups. WBC count
      was associated with more MetS components in whites than in blacks. Mean values of
      WBC increased significantly with increasing number of MetS components with
      adverse levels in adolescents and adults, with a stronger trend in whites. WBC
      count was longitudinally associated with MetS in whites only (P<0.001).
      CONCLUSIONS: The findings on the association between higher WBC count and MetS
      beginning in childhood, particularly in whites, underscore a potentially
      mechanistic link between systemic inflammation, MetS, and cardiovascular risk.

PMID- 20798337
TI  - The effect of iron and erythropoietin treatment on the A1C of patients with
      diabetes and chronic kidney disease.
AB  - OBJECTIVE: To examine the effect of intravenous iron and erythropoietin
      stimulating agents (ESAs) on glycemic control and A1C of patients with diabetes
      and chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: This was a
      prospective study of patients with type 2 diabetes and CKD stage IIIB or IV
      undergoing intravenous iron (group A) and/or ESA (group B). Full blood profiles
      were determined over the study period. Glycemic control was monitored using A1C,
      seven-point daily glucose three times weekly, and continuous glucose monitoring
      (CGM). RESULTS: There were 15 patients in both group A and group B. Mean A1C (95%
      CI) values fell in both groups (7.40% [6.60-8.19] to 6.96% [6.27-7.25], P<0.01,
      with intravenous iron and 7.31% [6.42-8.54] to 6.63% [6.03-7.36], P=0.013, ESA).
      There was no change in mean blood glucose in group A (9.55 mmol/l [8.20-10.90]
      vs. 9.71 mmol/l [8.29-11.13], P=0.07) and in group B (8.72 mmol/l [7.31-10.12]
      vs. 8.78 mmol/l [7.47-9.99], P=0.61) over the study period. Hemoglobin and
      hematocrit values significantly increased following both treatments. There was no
      linear relationship found between the change in A1C values and the rise of
      hemoglobin following either treatment. CONCLUSIONS: Both iron and ESA cause a
      significant fall in A1C values without a change to glycemic control in patients
      with diabetes and CKD. At the present time, regular capillary glucose
      measurements and the concurrent use of CGM remain the best alternative
      measurements of glycemic control in this patient group.

PMID- 20798338
TI  - Serum uric acid predicts progression of subclinical coronary atherosclerosis in
      individuals without renal disease.
AB  - OBJECTIVE: To examine uric acid (UA) as a possible predictor of the progression
      of coronary artery calcification (CAC) using data from the prospective Coronary
      Artery Calcification in Type 1 Diabetes (CACTI) Study. RESEARCH DESIGN AND
      METHODS: CAC was measured by electron beam tomography at the baseline and at a
      follow-up 6.0+/-0.5 years later. The study population included 443 participants
      with type 1 diabetes and 526 control subjects who were free of diagnosed coronary
      artery disease at baseline. The presence of renal disease was defined by the
      presence of albuminuria and/or low glomerular filtration rate. RESULTS: In
      subjects without renal disease, serum UA predicted CAC progression (odds ratio
      1.30 [95% CI 1.07-1.58], P=0.007) independent of conventional cardiovascular risk
      factors including diabetes and the presence of metabolic syndrome. CONCLUSIONS:
      Serum UA levels predict the progression of coronary atherosclerosis and may be
      useful in identifying who is at risk for vascular disease in the absence of
      significant chronic kidney disease.

PMID- 20798339
TI  - The role of blood pressure variability in the development of nephropathy in type
      1 diabetes.
AB  - OBJECTIVE: Increases in blood pressure and visit-to-visit variability have both
      been found to independently increase the likelihood of cardiovascular events in
      nondiabetic individuals. This study has investigated whether each may also
      influence the development of microvascular complications in type 1 diabetes by
      examining data from the Diabetes Control and Complications Trial (DCCT). RESEARCH
      DESIGN AND METHODS: Using binary longitudinal multiple logistic regression, mean
      systolic (SBP) and diastolic (DBP) blood pressure as well as annual visit-to
      visit variability (SD.SBP and SD.DBP, respectively) was related to the risk of
      the development/progression of nephropathy and retinopathy in initially
      normotensive subjects who did not become pregnant during the DCCT. RESULTS: Mean
      SBP and SD.SBP were independently predictive of albuminuria (odds ratio 1.005
      [95% CI 1.002-1.008], P<0.001 and 1.093 [1.069-1.117], P<0.001, respectively, for
      1 mmHg change), although SBP variability did not add to mean SBP in predicting
      retinopathy (0.999 [0.985-1.013], P=0.93). DBP variability was also independently
      predictive of nephropathy (1.102 [1.068-1.137], P<0.001) and not of retinopathy
      (0.991 [0.971-1.010], P=0.37). Mean SBP was poorly related to SD.SBP (r2<0.01) as
      was mean DBP with SD. DBP (r2<0.01). CONCLUSIONS: Visit-to-visit variability in
      blood pressure consistently independently added to mean blood pressure in
      predicting the risk of nephropathy, but not retinopathy, in the DCCT. This
      observation could have implications for the management and treatment of blood
      pressure in patients with type 1 diabetes.

PMID- 20798340
TI  - Label-free imaging, detection, and mass measurement of single viruses by surface
      plasmon resonance.
AB  - We report on label-free imaging, detection, and mass/size measurement of single
      viral particles in solution by high-resolution surface plasmon resonance
      microscopy. Diffraction of propagating plasmon waves along a metal surface by the
      viral particles creates images of the individual particles, which allow us to
      detect the binding of the viral particles to surfaces functionalized with and
      without antibodies. We show that the intensity of the particle image is related
      to the mass of the particle, from which we determine the mass and mass
      distribution of influenza viral particles with a mass detection limit of
      approximately 1 ag (or 0.2 fg/mm(2)). This work demonstrates a multiplexed method
      to measure the masses of individual viral particles and to study the binding
      activity of the viral particles.

PMID- 20798341
TI  - Charges in the hydrophobic interior of proteins.
AB  - Charges are inherently incompatible with hydrophobic environments. Presumably for
      this reason, ionizable residues are usually excluded from the hydrophobic
      interior of proteins and are found instead at the surface, where they can
      interact with bulk water. Paradoxically, ionizable groups buried in the
      hydrophobic interior of proteins play essential roles, especially in biological
      energy transduction. To examine the unusual properties of internal ionizable
      groups we measured the pK(a) of glutamic acid residues at 25 internal positions
      in a stable form of staphylococcal nuclease. Two of 25 Glu residues titrated with
      normal pK(a) near 4.5; the other 23 titrated with elevated pK(a) values ranging
      from 5.2-9.4, with an average value of 7.7. Trp fluorescence and far-UV circular
      dichroism were used to monitor the effects of internal charges on conformation.
      These data demonstrate that although charges buried in proteins are indeed
      destabilizing, charged side chains can be buried readily in the hydrophobic core
      of stable proteins without the need for specialized structural adaptations to
      stabilize them, and without inducing any major conformational reorganization. The
      apparent dielectric effect experienced by the internal charges is considerably
      higher than the low dielectric constants of hydrophobic matter used to represent
      the protein interior in electrostatic continuum models of proteins. The high
      thermodynamic stability required for proteins to withstand the presence of buried
      charges suggests a pathway for the evolution of enzymes, and it underscores the
      need to mind thermodynamic stability in any strategy for engineering novel or
      altered enzymatic active sites in proteins.

PMID- 20798342
TI  - Biomimetic cilia arrays generate simultaneous pumping and mixing regimes.
AB  - Living systems employ cilia to control and to sense the flow of fluids for many
      purposes, such as pumping, locomotion, feeding, and tissue morphogenesis. Beyond
      their use in biology, functional arrays of artificial cilia have been envisaged
      as a potential biomimetic strategy for inducing fluid flow and mixing in lab-on-a
      chip devices. Here we report on fluid transport produced by magnetically actuated
      arrays of biomimetic cilia whose size approaches that of their biological
      counterparts, a scale at which advection and diffusion compete to determine mass
      transport. Our biomimetic cilia recreate the beat shape of embryonic nodal cilia,
      simultaneously generating two sharply segregated regimes of fluid flow: Above the
      cilia tips their motion causes directed, long-range fluid transport, whereas
      below the tips we show that the cilia beat generates an enhanced diffusivity
      capable of producing increased mixing rates. These two distinct types of flow
      occur simultaneously and are separated in space by less than 5 microm,
      approximately 20% of the biomimetic cilium length. While this suggests that our
      system may have applications as a versatile microfluidics device, we also focus
      on the biological implications of our findings. Our statistical analysis of
      particle transport identifying an enhanced diffusion regime provides novel
      evidence for the existence of mixing in ciliated systems, and we demonstrate that
      the directed transport regime is Poiseuille-Couette flow, the first analytical
      model consistent with biological measurements of fluid flow in the embryonic
      node.

PMID- 20798343
TI  - Nanopore DNA sequencing with MspA.
AB  - Nanopore sequencing has the potential to become a direct, fast, and inexpensive
      DNA sequencing technology. The simplest form of nanopore DNA sequencing utilizes
      the hypothesis that individual nucleotides of single-stranded DNA passing through
      a nanopore will uniquely modulate an ionic current flowing through the pore,
      allowing the record of the current to yield the DNA sequence. We demonstrate that
      the ionic current through the engineered Mycobacterium smegmatis porin A, MspA,
      has the ability to distinguish all four DNA nucleotides and resolve single
      nucleotides in single-stranded DNA when double-stranded DNA temporarily holds the
      nucleotides in the pore constriction. Passing DNA with a series of double
      stranded sections through MspA provides proof of principle of a simple DNA
      sequencing method using a nanopore. These findings highlight the importance of
      MspA in the future of nanopore sequencing.

PMID- 20798344
TI  - Crystal engineering of lattice metrics of perhalometallate salts and MOFs.
AB  - The synthesis of the salt 3 and metallo-organic framework (MOF) [{(4,4(')
      bipy)CoBr(2)}(n)] 4 by a range of solid state (mechanochemical and
      thermochemical) and solution methods is reported; they are isostructural with
      their respective chloride analogues 1 and 2. 3 and 4 can be interconverted by
      means of HBr elimination and absorption. Single phases of controlled composition
      and general formula [4,4(')-H(2)bipy][CoBr(4-x)Cl(x)] 5(x) may be prepared from 2
      and 4 by solid--gas reactions involving HBr or HCl respectively. Crystalline
      single phase samples of 5(x) and [{(4,4(')-bipy)CoBr(2-x)Cl(x)}(n)] 6(x) were
      prepared by solid-state mechanochemical routes, allowing fine control over the
      composition and unit cell volume of the product. Collectively these methods
      enable continuous variation of the unit cell dimensions of the salts [4,4(')
      H(2)bipy][CoBr(4-x)Cl(x)] (5(x)) and the MOFs [{(4,4(')-bipy)CoBr(2-x)Cl(x)}(n)]
      (6(x)) by varying the bromide to chloride ratio and establish a means of
      controlling MOF composition and the lattice metrics, and so the physical and
      chemical properties that derive from it.

PMID- 20798345
TI  - G-quadruplex structures in RNA stimulate mitochondrial transcription termination
      and primer formation.
AB  - The human mitochondrial transcription machinery generates the primers required
      for initiation of leading-strand DNA replication. According to one model, the 3'
      end of the primer is defined by transcription termination at conserved sequence
      block II (CSB II) in the mitochondrial DNA control region. We here demonstrate
      that this site-specific termination event is caused by G-quadruplex structures
      formed in nascent RNA upon transcription of CSB II. We also demonstrate that a
      poly-dT stretch downstream of CSB II has a modest stimulatory effect on the
      termination efficiency. The mechanism is reminiscent of Rho-independent
      transcription termination in prokaryotes, with the exception that a G-quadruplex
      structure replaces the hairpin loop formed in bacterial mRNA during transcription
      of terminator sequences.

PMID- 20798346
TI  - Paracrinology of islets and the paracrinopathy of diabetes.
AB  - New results have brought to light the importance of the regulation of glucagon by
      beta-cells in the development of diabetes. In this perspective, we examine the
      normal paracrinology of alpha- and beta-cells in nondiabetic pancreatic islets.
      We propose a Sherringtonian model of coordinated reciprocal secretory responses
      of these juxtaposed cells that secrete glucagon and insulin, hormones with
      opposing actions on the liver. As insulin is a powerful inhibitor of glucagon, we
      propose that within-islet inhibition of alpha-cells by beta-cells creates an
      insulin-to-glucagon ratio that maintains glycemic stability even in extremes of
      glucose influx or efflux. By contrast, in type 1 diabetes mellitus, alpha-cells
      lack constant action of high insulin levels from juxtaposed beta-cells.
      Replacement with exogenous insulin does not approach paracrine levels of secreted
      insulin except with high doses that "overinsulinize" the peripheral insulin
      targets, thereby promoting glycemic volatility. Based on the stable normoglycemia
      of mice with type 1 diabetes during suppression of glucagon with leptin, we
      conclude that, in the absence of paracrine regulation of alpha-cells, tonic
      inhibition of alpha-cells improves the dysregulated glucose homeostasis. These
      results have considerable medical implications, as they suggest new approaches to
      normalize the extreme volatility of glycemia in diabetic patients.

PMID- 20798347
TI  - BK channels play a counter-adaptive role in drug tolerance and dependence.
AB  - Disturbance of neural activity by sedative drugs has been proposed to trigger a
      homeostatic response that resists unfavorable changes in net cellular
      excitability, leading to tolerance and dependence. The Drosophila slo gene
      encodes a BK-type Ca(2+)-activated K(+) channel implicated in functional
      tolerance to alcohol and volatile anesthetics. We hypothesized that increased
      expression of BK channels induced by these drugs constitutes the homeostatic
      adaptation conferring resistance to sedative drugs. In contrast to the dogmatic
      view that BK channels act as neural depressants, we show that drug-induced slo
      expression enhances excitability by reducing the neuronal refractory period.
      Although this neuroadaptation directly counters some effects of anesthetics, it
      also causes long-lasting enhancement of seizure susceptibility, a common symptom
      of drug withdrawal. These data provide a possible mechanism for the long-standing
      counter-adaptive theory for drug tolerance in which homeostatic adaptations
      triggered by drug exposure to produce drug tolerance become counter-adaptive
      after drug clearance and result in symptoms of dependence.

PMID- 20798348
TI  - Resolving postglacial phylogeography using high-throughput sequencing.
AB  - The distinction between model and nonmodel organisms is becoming increasingly
      blurred. High-throughput, second-generation sequencing approaches are being
      applied to organisms based on their interesting ecological, physiological,
      developmental, or evolutionary properties and not on the depth of genetic
      information available for them. Here, we illustrate this point using a low-cost,
      efficient technique to determine the fine-scale phylogenetic relationships among
      recently diverged populations in a species. This application of restriction site
      associated DNA tags (RAD tags) reveals previously unresolved genetic structure
      and direction of evolution in the pitcher plant mosquito, Wyeomyia smithii, from
      a southern Appalachian Mountain refugium following recession of the Laurentide
      Ice Sheet at 22,000-19,000 B.P. The RAD tag method can be used to identify
      detailed patterns of phylogeography in any organism regardless of existing
      genomic data, and, more broadly, to identify incipient speciation and genome-wide
      variation in natural populations in general.

PMID- 20798349
TI  - Signatures of founder effects, admixture, and selection in the Ashkenazi Jewish
      population.
AB  - The Ashkenazi Jewish (AJ) population has long been viewed as a genetic isolate,
      yet it is still unclear how population bottlenecks, admixture, or positive
      selection contribute to its genetic structure. Here we analyzed a large AJ cohort
      and found higher linkage disequilibrium (LD) and identity-by-descent relative to
      Europeans, as expected for an isolate. However, paradoxically we also found
      higher genetic diversity, a sign of an older or more admixed population but not
      of a long-term isolate. Recent reports have reaffirmed that the AJ population has
      a common Middle Eastern origin with other Jewish Diaspora populations, but also
      suggest that the AJ population, compared with other Jews, has had the most
      European admixture. Our analysis indeed revealed higher European admixture than
      predicted from previous Y-chromosome analyses. Moreover, we also show that
      admixture directly correlates with high LD, suggesting that admixture has
      increased both genetic diversity and LD in the AJ population. Additionally, we
      applied extended haplotype tests to determine whether positive selection can
      account for the level of AJ-prevalent diseases. We identified genomic regions
      under selection that account for lactose and alcohol tolerance, and although we
      found evidence for positive selection at some AJ-prevalent disease loci, the
      higher incidence of the majority of these diseases is likely the result of
      genetic drift following a bottleneck. Thus, the AJ population shows evidence of
      past founding events; however, admixture and selection have also strongly
      influenced its current genetic makeup.

PMID- 20798350
TI  - Mammalian endoplasmic reticulum stress sensor IRE1 signals by dynamic clustering.
AB  - Accumulation of misfolded proteins in the endoplasmic reticulum (ER) triggers the
      unfolded protein response (UPR), an intracellular signaling pathway that adjusts
      the protein folding capacity of the ER according to need. If homeostasis in the
      ER protein folding environment cannot be reestablished, cells commit to
      apoptosis. The ER-resident transmembrane kinase-endoribonuclease inositol
      requiring enzyme 1 (IRE1) is the best characterized UPR signal transduction
      molecule. In yeast, Ire1 oligomerizes upon activation in response to an
      accumulation of misfolded proteins in the ER. Here we show that the salient
      mechanistic features of IRE1 activation are conserved: mammalian IRE1
      oligomerizes in the ER membrane and oligomerization correlates with the onset of
      IRE1 phosphorylation and RNase activity. Moreover, the kinase/RNase module of
      human IRE1 activates cooperatively in vitro, indicating that formation of
      oligomers larger than four IRE1 molecules takes place upon activation. High-order
      IRE1 oligomerization thus emerges as a conserved mechanism of IRE1 signaling.
      IRE1 signaling attenuates after prolonged ER stress. IRE1 then enters a
      refractive state even if ER stress remains unmitigated. Attenuation includes
      dissolution of IRE1 clusters, IRE1 dephosphorylation, and decline in
      endoribonuclease activity. Thus IRE1 activity is governed by a timer that may be
      important in switching the UPR from the initially cytoprotective phase to the
      apoptotic mode.

PMID- 20798352
TI  - Larry Kricka.

PMID- 20798351
TI  - Hepatic long-chain acyl-CoA synthetase 5 mediates fatty acid channeling between
      anabolic and catabolic pathways.
AB  - Long-chain acyl-CoA synthetases (ACSLs) and fatty acid transport proteins (FATPs)
      activate fatty acids (FAs) to acyl-CoAs prior to their downstream metabolism. Of
      numerous ACSL and FATP isoforms, ACSL5 is expressed predominantly in tissues with
      high rates of triacylglycerol (TAG) synthesis, suggesting it may have an anabolic
      role in lipid metabolism. To characterize the role of ACSL5 in hepatic energy
      metabolism, we used small interference RNA (siRNA) to knock down ACSL5 in rat
      primary hepatocytes. Compared with cells transfected with control siRNA,
      suppression of ACSL5 expression significantly decreased FA-induced lipid droplet
      formation. These findings were further extended with metabolic labeling studies
      showing that ACSL5 knockdown resulted in decreased [1-(14)C]oleic acid or acetic
      acid incorporation into intracellular TAG, phospholipids, and cholesterol esters
      without altering FA uptake or lipogenic gene expression. ACSL5 knockdown also
      decreased hepatic TAG secretion proportionate to the observed decrease in neutral
      lipid synthesis. ACSL5 knockdown did not alter lipid turnover or mediate the
      effects of insulin on lipid metabolism. Hepatocytes treated with ACSL5 siRNA had
      increased rates of FA oxidation without changing PPAR-alpha activity and target
      gene expression. These results suggest that ACSL5 activates and channels FAs
      toward anabolic pathways and, therefore, is an important branch point in hepatic
      FA metabolism.

PMID- 20798353
TI  - Plasma YKL-40 and total and disease-specific mortality in the general population.
AB  - BACKGROUND: Increased plasma YKL-40 is associated with short-term survival in
      patients with cardiovascular disease and cancer. We tested the hypothesis that
      increased plasma YKL-40 is associated with total and disease-specific mortality
      in the general population. METHODS: We measured plasma YKL-40 in 8899 study
      participants, aged 20-95 years, in the Copenhagen City Heart Study from the
      Danish general population who were followed for 16 years: 3059 died, 2158 had
      ischemic cardiovascular disease, 2271 had cancer, and 2820 had other diseases
      associated with increased YKL-40. Hazard ratios for early death and absolute 10
      year mortality rates were calculated according to plasma YKL-40 percentile
      groupings computed within sex and age decade: 0%-33%, 34%-66%, 67%-90%, 91%-95%,
      and 96%-100%. RESULTS: Median survival age decreased from 83 years for
      participants with plasma YKL-40 in category 0%-33% to 69 years in category 96%
      100% (trend, P < 0.0001). Risk of early death was increased (multifactorially
      adjusted hazard ratios) by 10% for YKL-40 category 34%-66%, by 30% for 67%-90%,
      by 70% for 91%-95%, and by 90% for 96%-100% vs YKL-40 category 0%-33% (trend, P <
      0.0001). Corresponding increases in participants with ischemic cardiovascular
      disease were 10%, 20%, 80%, and 60% (P < 0.0001); in those with cancer were 10%,
      20%, 50%, and 70% (P < 0.0001); and in those with other diseases were 10%, 20%,
      40%, and 60% (P < 0.0001). Highest absolute 10-year mortality rates were 78% and
      90% in women and men, respectively, who were >70 years old, smoked, and were in
      YKL-40 category 96%-100%. CONCLUSIONS: Increased plasma YKL-40 is associated with
      risk of early death from cardiovascular disease, cancer, and other diseases in
      the general population.

PMID- 20798354
TI  - Simplified method for international normalized ratio (INR) derivation based on
      the prothrombin time/INR line: an international study.
AB  - BACKGROUND: The need to perform local International Sensitivity Index (ISI)
      calibrations and in particular the requirement for a manual method for
      prothrombin time (PT) determination, have proved to be obstacles to application
      of the WHO scheme for PT standardization. METHODS: We used international
      normalized ratio (INR) derived with a set of only 5 European Concerted Action on
      Anticoagulation (ECAA) lyophilized calibrant plasmas, certified manually by
      expert centers with reference thromboplastins, to determine a local PT/INR Line.
      We compared results of an independent set of validation plasmas with INRs from
      conventional ISI calibrations and with manually certified INRs. RESULTS: The mean
      certified INR of 5 lyophilized validation plasmas was 2.41 with human
      thromboplastin, 2.04 with bovine/combined, and 2.80 with rabbit. With 42 human
      reagents, the mean observed INR of the validation plasmas was 2.68 (11.2%
      deviation from certified INR). Deviation was reduced to 0.4% with both local ISI
      calibration and the PT/INR Line. Eight results based on bovine/combined
      thromboplastin gave an INR deviation of 4.9%, becoming 0.5% after ISI calibration
      and 2.4% with the PT/INR Line. Six results with rabbit reagents deviated from
      certified INR by 2.5%. After ISI calibration, deviation became 1.1%, and with the
      PT/INR Line, 0.7%. The PT/INR Line gave similar results with both linear and
      orthogonal regression analysis. The total proportion of validation plasmas giving
      INR within 10% deviation from certified values was 42.5% with uncorrected INR,
      which increased to 92.1% with local ISI calibration and 93.2% with the PT/INR
      Line. CONCLUSIONS: The PT/INR Line procedure with 5 ECAA calibrant plasmas
      successfully substitutes for local ISI calibrations in deriving reliable INRs.

PMID- 20798355
TI  - Regional differences of the effects of acetylcholine in the human gastric
      circular muscle.
AB  - The motor functions of the stomach have traditionally been regarded to have
      regional differences. However, to date there have been only a few data
      investigating whether such regional differences in motor function exist in the
      human stomach. The aims of the present study were to examine the spontaneous
      activity and responses to acetylcholine in the anatomically defined regions of
      human stomach. Human gastric circular muscle tissues from fundus, corpus, and
      antrum were obtained from 25 patients (14 men, 11 women with a mean age of 55.2
      yr; 36-74 yr) undergoing gastrectomy for gastric cancers. Isometric force
      measurements were performed by using muscle strips from the different regions of
      the human stomach under basal conditions and in response to the exogenous
      application of acetylcholine. Spontaneous phasic contractions were observed in
      all human gastric smooth muscles. However, the responses to acetylcholine
      displayed regional differences. In the gastric antrum, there was a dose-dependent
      increase in the peak contraction, contractile frequency, and amplitude of
      contraction after acetylcholine exposure (up to 1 MUM). However, there was no
      significant change in the basal tone. In the corpus and fundus, acetylcholine
      induced a dose-dependent increase in the peak contraction and basal tone.
      However, there was no significant change in the contractile frequency or
      amplitude of contraction. In conclusion, the response of human gastric circular
      muscle to acetylcholine displayed regional differences between the antrum and the
      corpus and fundus. This finding suggested the presence of distinct functional
      regions in human stomach.

PMID- 20798356
TI  - CCK-independent mTORC1 activation during dietary protein-induced exocrine
      pancreas growth.
AB  - Dietary protein can stimulate pancreatic growth in the absence of CCK release,
      but there is little data on the regulation of CCK-independent growth. To identify
      mechanisms whereby protein stimulates pancreatic growth in the absence of CCK
      release, C57BL/6 control and CCK-null male mice were fed normal-protein (14%
      casein) or high-protein (75% casein) chow for 7 days. The weight of the pancreas
      increased by 32% in C57BL/6 mice and 26% in CCK-null mice fed high-protein chow.
      Changes in pancreatic weight in control mice were due to both cell hypertrophy
      and hyperplasia since there was an increase in protein-to-DNA ratio, total DNA
      content, and DNA synthesis. In CCK-null mice pancreatic growth was almost
      entirely due to hypertrophy with both protein-to-DNA ratio and cell size
      increasing without significant increases in DNA content or DNA synthesis. ERK,
      calcineurin, and mammalian target of rapamycin complex 1 (mTORC1) are activated
      in models of CCK-induced growth, but there were no differences in ERK or
      calcineurin activation between fasted and fed CCK-null mice. In contrast, mTORC1
      activation was increased after feeding and the duration of activation was
      prolonged in mice fed high-protein chow compared with normal-protein chow.
      Changes in pancreatic weight and RNA content were completely inhibited, and
      changes in protein content were partially abated, when the mTORC1 inhibitor
      rapamycin was administered during high-protein chow feeding. Prolonged mTORC1
      activation is thus required for dietary protein-induced pancreatic growth in the
      absence of CCK.

PMID- 20798357
TI  - Human-derived probiotic Lactobacillus reuteri strains differentially reduce
      intestinal inflammation.
AB  - Lactobacillus reuteri (L. reuteri) is a probiotic that inhibits the severity of
      enteric infections and modulates the immune system. Human-derived L. reuteri
      strains DSM17938, ATCC PTA4659, ATCC PTA 5289, and ATCC PTA 6475 have
      demonstrated strain-specific immunomodulation in cultured monocytoid cells, but
      information about how these strains affect inflammation in intestinal epithelium
      is limited. We determined the effects of the four different L. reuteri strains on
      lipopolysaccharide (LPS)-induced inflammation in small intestinal epithelial
      cells and in the ileum of newborn rats. IPEC-J2 cells (derived from the jejunal
      epithelium of a neonatal piglet) and IEC-6 cells (derived from the rat crypt)
      were treated with L. reuteri. Newborn rat pups were gavaged cow milk formula
      supplemented with L. reuteri strains in the presence or absence of LPS. Protein
      and mRNA levels of cytokines and histological changes were measured. We
      demonstrate that even though one L. reuteri strain (DSM 17938) did not inhibit
      LPS-induced IL-8 production in cultured intestinal cells, all strains
      significantly reduced intestinal mucosal levels of KC/GRO (~IL-8) and IFN-gamma
      when newborn rat pups were fed formula containing LPS +/- L. reuteri. Intestinal
      histological damage produced by LPS plus cow milk formula was also significantly
      reduced by all four strains. Cow milk formula feeding (without LPS) produced mild
      gut inflammation, evidenced by elevated mucosal IFN-gamma and IL-13 levels, a
      process that could be suppressed by strain 17938. Other cytokines and chemokines
      were variably affected by the different strains, and there was no toxic effect of
      L. reuteri on intestinal cells or mucosa. In conclusion, L. reuteri strains
      differentially modulate LPS-induced inflammation. Probiotic interactions with
      both epithelial and nonepithelial cells in vivo must be instrumental in
      modulating intrinsic anti-inflammatory effects in the intestine. We suggest that
      the terms anti- and proinflammatory be used only to describe the effects of a
      probiotic in the living host.

PMID- 20798358
TI  - Roles of prostaglandin E2-EP1 receptor signaling in regulation of gastric motor
      activity and emptying.
AB  - It is widely accepted that the inhibition of gastric motor activity as well as
      the maintenance of gastric mucosal blood flow and mucous secretion are important
      for the homeostasis of the gastric mucosa. The present study was performed to
      ascertain whether or not endogenous PGs, which can protect the stomach from
      noxious stimuli, affect gastric motor activity and emptying. The myoelectrical
      activity of rat gastric smooth muscle was increased at intragastric pressures of
      over 2 cmH(2)O. Replacement of intragastric physiological saline with 1 M NaCl
      solution significantly increased PGI(2) and PGE(2) in stomach and suppressed the
      myoelectrical activity under a pressure of 2 cmH(2)O by 70%. Indomethacin
      inhibited the suppression of myoelectrical activity by 1 M NaCl. The
      myoelectrical activity under a pressure of 2 cmH(2)O was suppressed by continuous
      infusion of a selective EP1 agonist (ONO-DI-004, 3-100 nmol.kg(-1).min(-1)) into
      the gastric artery in a dose-dependent manner, but not by that of the PGI
      receptor agonist beraprost sodium (100 nmol.kg(-1).min(-1)). Suppression of
      myoelectrical activity with 1 M NaCl was inhibited by continuous infusion of a
      selective EP1 antagonist (ONO-8711, 100 nmol.kg(-1).min(-1)) into the gastric
      artery. Furthermore, gastric emptying was tested in EP1 knockout mice and their
      wild-type counterparts. Gastric emptying was strongly suppressed with
      intragastric 1 M NaCl in wild-type mice, but this 1 M NaCl-induced suppression
      was not seen in EP1 knockout mice. These results suggest that PGE(2)-EP1
      signaling has crucial roles in suppression of myoelectrical activity of gastric
      smooth muscles and inhibition of gastric emptying and that EP1 is an obvious
      target for drugs that control gastric emptying.

PMID- 20798359
TI  - Disruption of protein arginine N-methyltransferase 2 regulates leptin signaling
      and produces leanness in vivo through loss of STAT3 methylation.
AB  - RATIONALE: Arginine methylation by protein N-arginine methyltransferases (PRMTs)
      is an important posttranslational modification in the regulation of protein
      signaling. PRMT2 contains a highly conserved catalytic Ado-Met binding domain,
      but the enzymatic function of PRMT2 with respect to methylation is unknown. The
      JAK-STAT pathway is proposed to be regulated through direct arginine methylation
      of STAT transcription factors, and STAT3 signaling is known to be required for
      leptin regulation of energy balance. OBJECTIVE: To identify the potential role of
      STAT3 arginine methylation by PRMT2 in the regulation of leptin signaling and
      energy homeostasis. METHODS AND RESULTS: We identified that PRMT2(-/-) mice are
      hypophagic, lean, and have significantly reduced serum leptin levels. This lean
      phenotype is accompanied by resistance to food-dependent obesity and an increased
      sensitivity to exogenous leptin administration. PRMT2 colocalizes with STAT3 in
      hypothalamic nuclei, where it binds and methylates STAT3 through its Ado-Met
      binding domain. In vitro studies further clarified that the Ado-Met binding
      domain of PRMT2 induces STAT3 methylation at the Arg31 residue. Absence of PRMT2
      results in decreased methylation and prolonged tyrosine phosphorylation of
      hypothalamic STAT3, which was associated with increased expression of
      hypothalamic proopiomelanocortin following leptin stimulation. CONCLUSIONS: These
      data elucidate a molecular pathway that directly links arginine methylation of
      STAT3 by PRMT2 to the regulation of leptin signaling, suggesting a potential role
      for PRMT2 antagonism in the treatment of obesity and obesity-related syndromes.

PMID- 20798360
TI  - Pioglitazone-induced reductions in atherosclerosis occur via smooth muscle cell
      specific interaction with PPAR{gamma}.
AB  - RATIONALE: Peroxisome proliferator-activated receptor (PPAR)gamma agonists
      attenuate atherosclerosis and abdominal aortic aneurysms (AAAs). PPARgamma, a
      nuclear receptor, is expressed on many cell types including smooth muscle cells
      (SMCs). OBJECTIVE: To determine whether a PPARgamma agonist reduces angiotensin
      II (Ang II)-induced atherosclerosis and AAAs via interaction with SMC-specific
      PPARgamma. METHODS AND RESULTS: Low-density lipoprotein receptor (LDLR)(-/-) mice
      with SMC-specific PPARgamma deficiency were developed using PPARgamma floxed
      (PPARgamma(f/f)) and SM22 Cre(+) mice. PPARgamma(f/f) littermates were generated
      that did not express Cre (Cre(0/0)) or were hemizygous for Cre (Cre(+/0)). To
      assess the contribution of SMC-specific PPARgamma in ligand-mediated attenuation
      of Ang II-induced atherosclerosis and AAAs, both male and female Cre(0/0) and
      Cre(+/0) mice were fed a fat-enriched diet with or without the PPARgamma agonist
      pioglitazone (Pio) (20 mg/kg per day) for 5 weeks. After 1 week of feeding
      modified diets, mice were infused with Ang II (1000 ng/kg per minute) for 4
      weeks. SMC-specific PPARgamma deficiency or Pio administration had no effect on
      plasma cholesterol concentrations. Pio administration attenuated Ang II-increased
      systolic blood pressure equivalently in both Cre(0/0) and Cre(+/0) groups. SMC
      specific PPARgamma deficiency increased atherosclerosis in male mice. Pio
      administration reduced atherosclerosis in only the Cre(0/0) mice, but not in mice
      with SMC-specific PPARgamma deficiency. SMC-specific PPARgamma deficiency or Pio
      administration had no effect on Ang II-induced AAA development. Pio also did not
      attenuate Ang II-induced monocyte chemoattractant protein-1 production in
      PPARgamma-deficient SMCs. CONCLUSIONS: Pio attenuates Ang II-induced
      atherosclerosis via the interaction with SMC-specific PPARgamma, but has no
      effect on the development of AAAs.

PMID- 20798361
TI  - Local regulation of arterial L-type calcium channels by reactive oxygen species.
AB  - RATIONALE: Reactive oxygen species (ROS) are implicated in the development of
      cardiovascular disease, and oxidants are important signaling molecules in many
      cell types. Recent evidence suggests that localized subcellular
      compartmentalization of ROS generation is an important feature of ROS signaling.
      However, mechanisms that transduce localized subcellular changes in redox status
      to functionally relevant changes in cellular processes such as Ca(2+) influx are
      poorly understood. OBJECTIVE: To test the hypothesis that ROS regulate L-type
      Ca(2+) channel activity in cerebral arterial smooth muscle. METHODS AND RESULTS:
      Using a total internal reflection fluorescence imaging-based approach, we found
      that highly localized subplasmalemmal generation of endogenous ROS preceded and
      colocalized with sites of enhanced L-type Ca(2+) channel sparklet activity in
      isolated cerebral arterial smooth muscle cells. Consistent with this observation
      and our hypothesis, exogenous ROS increased localized L-type Ca(2+) channel
      sparklet activity in isolated arterial myocytes via activation of protein kinase
      Calpha and when applied to intact cerebral arterial segments, exogenous ROS
      increased arterial tone in an L-type Ca(2+) channel-dependent fashion.
      Furthermore, angiotensin II-dependent stimulation of local L-type Ca(2+) channel
      sparklet activity in isolated cells and contraction of intact arteries was
      abolished following inhibition of NADPH oxidase. CONCLUSIONS: Our data support a
      novel model of local oxidative regulation of Ca(2+) influx where vasoconstrictors
      coupled to NAPDH oxidase (eg, angiotensin II) induce discrete sites of ROS
      generation resulting in oxidative activation of adjacent protein kinase Calpha
      molecules that in turn promote local sites of enhanced L-type Ca(2+) channel
      activity, resulting in increased Ca(2+) influx and contraction.

PMID- 20798362
TI  - Intravenous thrombolysis in patients older than age 80 years.

PMID- 20798363
TI  - Stroke monitoring on a national level: PERFECT Stroke, a comprehensive, registry
      linkage stroke database in Finland.
AB  - BACKGROUND AND PURPOSE: Stroke databases are established to systematically
      evaluate both the treatment and outcome of stroke patients and the structure and
      processes of stroke services. Comprehensive data collection on this common
      disease is resource-intensive, and national stroke databases often include only
      patients from selected hospitals. Here we describe an alternative national stroke
      database. METHODS: We established a nationwide stroke database with multiple
      administrative registry linkages at the individual-patient level. Information on
      comorbidities; treatments before, during, and after stroke; living status;
      recurrences; case fatality; and costs were collected for each hospital-treated
      stroke patient. RESULTS: The current database includes 94 316 patients with
      incident stroke between January 1999 and December 2007, with follow-up until
      December 2008. Annually, 10 500 new patients are being added. One-year recurrence
      was 13% and case fatality was 27% during the study period. In 2007, 86% of
      patients survived 1 month and 77% were living at home at 3 months, but the
      proportion treated in stroke centers (62%) or with nationally recommended
      secondary preventive medication after ischemic stroke (49%) was still suboptimal.
      CONCLUSIONS: In comparison with other national stroke databases, our method
      enables higher coverage and more thorough follow-up of patients. Information on
      long-term recurrences, case fatality, or costs is not often included in national
      stroke databases. Our database has low maintenance costs, but it lacks detailed
      data on in-hospital processes. Use of national administrative data, where such
      linkage is possible, saves resources, achieves high rates of long-term follow-up,
      and allows for comprehensive monitoring of the burden of the disease.

PMID- 20798364
TI  - Effect of thermal stimulation on upper extremity motor recovery 3 months after
      stroke.
AB  - BACKGROUND AND PURPOSE: To examine the effect of thermal stimulation (TS) on
      upper extremity (UE) motor recovery in patients at least 3 months after stroke.
      METHODS: Participants were randomly assigned to either the experimental group or
      the control group. In addition to regular rehabilitation programs, the
      experimental group received an UE-TS protocol for 30 minutes per day (3 days/week
      for 8 weeks); the control group received the same TS protocol on lower extremity.
      The UE subscale of the Stroke Rehabilitation Assessment of Movement and the
      Action Research Arm Test were primary outcome measures. The Modified Ashworth
      Scale and the Barthel Index were secondary outcome measures. All measures were
      administered at baseline, after TS, and at 1-month follow-up. RESULTS: Twenty
      three participants (12 in the experimental group) completed the study. After
      treatment, the experimental group showed significant improvement compared to the
      control group in the scores of the UE subscale of the Stroke Rehabilitation
      Assessment of Movement and Action Research Arm Test. At follow-up examination, a
      significant improvement in the experimental group was observed on the UE subscale
      of the Stroke Rehabilitation Assessment of Movement. CONCLUSIONS: The 8-week
      additional UE-TS protocol improved UE motor recovery for stroke patients 3 months
      after onset.

PMID- 20798365
TI  - Association between basilar artery hypoplasia and undetermined or lacunar
      posterior circulation ischemic stroke.
AB  - BACKGROUND AND PURPOSE: The aim of the current study was to determine the
      prevalence of basilar artery hypoplasia (BAH) and to evaluate whether BAH is a
      possible risk factor for posterior circulation stroke (PCS). METHODS: Basilar
      artery diameter was assessed by MRI in 685 consecutive ischemic stroke patients.
      BAH frequency, defined as a diameter <2 mm, was measured and compared between
      anterior circulation stroke and PCS groups. RESULTS: Thirty-seven patients had
      BAH (5.2%): 15 of 195 (7.7%) in PCS and 22 of 490 (4.5%) in anterior circulation
      stroke (P=0.2). In undetermined or lacunar stroke patients, BAH frequency was
      higher in PCS than in anterior circulation stroke (14/97, 14.4% vs 10/216, 4.6%;
      P=0.005). National Institutes of Health Stroke Scale score was <4 in 65%.
      Localization of stroke was predominant in pons or cerebellar territories (71.4%).
      Half of PCS and BAH patients showed small pontic-penetrating arteries infarcts.
      CONCLUSIONS: Our study suggests that BAH is associated with PCS in lacunar or
      undetermined stroke. Patients often had minor stroke and infarctions that were
      usually small and frequently located in pontine-penetrating artery territories.

PMID- 20798366
TI  - How much would performing diffusion-weighted imaging for all transient ischemic
      attacks increase MRI utilization?
AB  - OBJECTIVES: The American Heart Association recently redefined TIA to exclude
      patients with infarction on neuroimaging. Given its advantages, MRI/diffusion
      weighted imaging (DWI) was recommended as the preferred imaging modality. We
      determined how frequently MRI/DWI was performed for TIA and ascertained the
      proportion of clinically defined TIA patients who had ischemic lesions on DWI in
      our community in 2005. METHODS: All clinically defined TIA cases among residents
      of a 5-county region around Cincinnati who presented to emergency departments
      were identified during 2005. Demographics and medical history, whether MRI/DWI
      was performed, and DWI findings were recorded. Generalized estimating equations
      were used to compare groups to account for the design of the study and multiple
      events per patient. RESULTS: Of 834 TIA events in 799 patients, 323 events (40%)
      had MRI/DWI performed. Patients who had MRI/DWI were younger (mean, 66 vs 70
      years; P=0.03), had less severe prestroke disability (baseline modified Rankin
      Scale score, 0; 44% vs 34%; P=0.02), were less likely to have previous stroke or
      TIA (42% vs 56%; P=0.002), and were less likely to have atrial fibrillation (10%
      vs 16%; P=0.01). Of the 323 events with DWI, 51 (15%) had evidence of acute
      infarction. Patients with positive DWI were older (75 vs 64 years; P=0.0001) and
      more likely to have atrial fibrillation (21% vs 7%; P=0.002). CONCLUSIONS:
      Performing MRI/DWI on all clinically defined TIA patients in our community would
      reveal more cases of actual infarction but would more than double current use.
      Future studies should assess whether MRI/DWI is warranted for all TIA patients.

PMID- 20798367
TI  - Risk of early carotid endarterectomy for symptomatic carotid stenosis.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine and compare
      the rate of stroke, myocardial infarction, and death in patients undergoing early
      and late carotid endarterectomy (CEA) after a symptomatic event and in
      asymptomatic patients. METHODS: We conducted a retrospective analysis of all CEAs
      performed in the Department of Neurosurgery between January 2004 and May 2009.
      Patients were divided into 3 groups: Group 1, asymptomatic patients; Group 2,
      symptomatic patients operated on >2 weeks after their transient ischemic attack
      or stroke; and Group 3, symptomatic patients operated on <=2 weeks of their
      transient ischemic attack or stroke. Primary outcomes were any myocardial
      infarction, stroke, or death occurring within 30 days postoperatively. The
      secondary end point was transient ischemic attack within 30 days postoperatively.
      RESULTS: Five hundred thirty-two CEAs were performed on 507 patients during the
      study period. Thirty-day follow-up was available for 500 patients with 525 CEAs.
      Groups 1, 2, and 3 consisted of 278, 105, and 142 CEAs, respectively. In total,
      12 patients had primary outcomes. In Group 1, 5 patients had primary outcomes of
      stroke, myocardial infarction, or death (1.8%); in Group 2, 1 patient had primary
      outcomes (1.0%); and in Group 3, 6 patients had primary outcomes (4.2%). There
      was no significant difference in the rate of primary outcomes among the 3 groups
      (P=0.17) or when Groups 2 and 3 were compared (P=0.24). CONCLUSIONS: Although the
      perioperative risk of transient ischemic attacks, stroke, death, and myocardial
      infarction is slightly higher in symptomatic patients operated on early, CEA can
      be done with an acceptable risk in properly selected symptomatic patients within
      2 weeks of their transient ischemic attack or stroke.

PMID- 20798368
TI  - Correlation of echocardiographic findings with cerebral infarction in elderly
      adults: the AGES-Reykjavik study.
AB  - BACKGROUND AND PURPOSE: Chronic effects of hypertension may be observed in
      multiple end organs. Previous reports suggest that cardiovascular morphological
      features can mirror cerebral infarction. In this cross-sectional analysis of
      elderly subjects, we investigated the relationship of a comprehensive set of
      echocardiographic measures with cerebral infarction detected by MRI. METHODS: We
      compared echocardiographically determined left ventricular (LV) mass, left atrial
      volume, aortic root diameter, mitral annular calcification, and measures of
      diastolic function with cerebral infarction determined by MRI using logistic
      regression in a random sample drawn from the Age Gene/Environment Susceptibility
      Reykjavik Study cohort. The model was first adjusted for age and gender, and then
      for age, gender, and vascular risk factors. RESULTS: Among 692 subjects aged 75
      (standard deviation, 6) years, 28% had at least 1 cerebral infarct. When adjusted
      for age and gender, the presence of cerebral infarction was modestly related to
      LV mass (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.02) and left
      atrial volume (OR, 1.03; 95% CI, 1.01-1.05), as well as the lowest quartile of
      early-to-late pulsed Doppler velocity ratio (early-to-late pulsed Doppler
      velocity ratio <0.75; OR, 1.87; 95% CI, 1.22-2.87). The latter relation remained
      significant after adjustment for vascular risk factors and LV ejection fraction
      (OR, 1.82; 95% CI, 1.16-2.86). CONCLUSIONS: Of all echocardiographic parameters,
      LV filling abnormality as indicated by low early-to-late pulsed Doppler velocity
      ratio displayed the strongest association with cerebral infarction and this
      relationship was independent of vascular risk factors. This simple marker of
      cerebral infarction may be useful when evaluating older patients.

PMID- 20798369
TI  - Flow-diverter stent for the endovascular treatment of intracranial aneurysms: a
      prospective study in 29 patients with 34 aneurysms.
AB  - BACKGROUND AND PURPOSE: The purpose of this study is to report our preliminary
      experience with the flow-diverter Silk stent for the endovascular treatment of
      intracranial aneurysms. METHODS: This prospective study was approved by the
      authors' ethical committees. Twenty-nine patients with 34 fusiform or wide-necked
      unruptured aneurysms were included and treated by Silk stent placement alone by 2
      physicians in 3 different centers. Technical issues, immediate findings, delayed
      complications, clinical follow-up, and imaging follow-up at 3 and 6 months were
      assessed. RESULTS: Endovascular treatment was successfully performed in 26
      patients (90%). In 3 patients, the stent could not be delivered. Mortality and
      morbidity rates were of 4% (1 of 26) and 15% (4 of 26), respectively; 1 patient
      died from a delayed aneurysm rupture related to stent migration, 3 experienced a
      thromboembolic event, and 1 patient developed progressive visual disturbances
      related to an increased mass effect. Clinical outcome in 25 patients was
      unchanged (n=19), improved (n=2), or worsened (=4). Angiographic follow-up in 24
      patients (29 aneurysms) showed 20 complete occlusions (69%), 1 neck remnant
      (3.5%), and 8 incomplete occlusions (27.5%). Significant parent artery stenosis
      at 6 months occurred in 8 cases (33%). CONCLUSIONS: Despite the potential
      interest of the Silk flow-diverter stent to treat complex intracranial aneurysms
      without coils, the delayed complication rate is quite high and leads to use this
      technique only in selective cases.

PMID- 20798370
TI  - Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage
      as an outcome event in clinical trials and observational studies: proposal of a
      multidisciplinary research group.
AB  - BACKGROUND AND PURPOSE: In clinical trials and observational studies there is
      considerable inconsistency in the use of definitions to describe delayed cerebral
      ischemia (DCI) after aneurysmal subarachnoid hemorrhage. A major cause for this
      inconsistency is the combining of radiographic evidence of vasospasm with
      clinical features of cerebral ischemia, although multiple factors may contribute
      to DCI. The second issue is the variability and overlap of terms used to describe
      each phenomenon. This makes comparisons among studies difficult. METHODS: An
      international ad hoc panel of experts involved in subarachnoid hemorrhage
      research developed and proposed a definition of DCI to be used as an outcome
      measure in clinical trials and observational studies. We used a consensus
      building approach. RESULTS: It is proposed that in observational studies and
      clinical trials aiming to investigate strategies to prevent DCI, the 2 main
      outcome measures should be: (1) cerebral infarction identified on CT or MRI or
      proven at autopsy, after exclusion of procedure-related infarctions; and (2)
      functional outcome. Secondary outcome measure should be clinical deterioration
      caused by DCI, after exclusion of other potential causes of clinical
      deterioration. Vasospasm on angiography or transcranial Doppler can also be used
      as an outcome measure to investigate proof of concept but should be interpreted
      in conjunction with DCI or functional outcome. CONCLUSIONS: The proposed measures
      reflect the most relevant morphological and clinical features of DCI without
      regard to pathogenesis to be used as an outcome measure in clinical trials and
      observational studies.

PMID- 20798371
TI  - Gene expression profiling of blood for the prediction of ischemic stroke.
AB  - BACKGROUND AND PURPOSE: A blood-based biomarker of acute ischemic stroke would be
      of significant value in clinical practice. This study aimed to (1) replicate in a
      larger cohort our previous study using gene expression profiling to predict
      ischemic stroke; and (2) refine prediction of ischemic stroke by including
      control groups relevant to ischemic stroke. METHODS: Patients with ischemic
      stroke (n=70, 199 samples) were compared with control subjects who were healthy
      (n=38), had vascular risk factors (n=52), and who had myocardial infarction
      (n=17). Whole blood was drawn <=3 hours, 5 hours, and 24 hours after stroke onset
      and from control subjects. RNA was processed on whole genome microarrays. Genes
      differentially expressed in ischemic stroke were identified and analyzed for
      predictive ability to discriminate stroke from control subjects. RESULTS: The 29
      probe sets previously reported predicted a new set of ischemic strokes with 93.5%
      sensitivity and 89.5% specificity. Sixty- and 46-probe sets differentiated
      control groups from 3-hour and 24-hour ischemic stroke samples, respectively. A
      97-probe set correctly classified 86% of ischemic strokes (3 hour+24 hour), 84%
      of healthy subjects, 96% of vascular risk factor subjects, and 75% with
      myocardial infarction. CONCLUSIONS: This study replicated our previously reported
      gene expression profile in a larger cohort and identified additional genes that
      discriminate ischemic stroke from relevant control groups. This multigene
      approach shows potential for a point-of-care test in acute ischemic stroke.

PMID- 20798372
TI  - Isolated vein thrombosis of the posterior fossa presenting as localized
      cerebellar venous infarctions or hemorrhages.
AB  - BACKGROUND AND PURPOSE: Cerebellar venous infarction or hemorrhage due to
      isolated venous thrombosis of the posterior fossa is a rare form of intracranial
      vein thrombosis that can be unsuspected in clinical practice. METHODS: We studied
      230 patients with intracranial vein thrombosis, identifying 9 (3.9%: 7 women,
      mean age 34 years) with neuroimaging or histopathologic evidence of localized
      posterior fossa vein thrombosis causing parenchymal injury limited exclusively to
      the cerebellum. RESULTS: All patients had an insidious presentation suggesting
      other diagnoses. Intracranial hypertension (n=6) and cerebellar (n=4) syndromes
      were the main clinical presentations. Intracranial vein thrombosis was idiopathic
      in 3 patients; associated with puerperium in 3; and with contraceptives, protein
      C deficiency, and dehydration in 1 case each. CT was abnormal but not diagnostic
      in 5 patients, showing a cerebellar hypodensity with fourth ventricle compression
      and variable hydrocephalus in 5 patients, and cerebellar hemorrhage in 2.
      Conventional MRI provided diagnosis in 6 cases, showing the causal thrombosis and
      cerebellar involvement; angiography was practiced in 2 of them, confirming the
      findings identified by MRI. In the other 3 patients, diagnosis was reached by
      histopathology. Thromboses were localized at the straight sinus (n=4), lateral
      sinuses (n=3), and superior petrosal vein (n=2). The acute case fatality rate was
      22.2% (n=2), 1 (11.1%) patient was discharged in a vegetative state, 1 (11.1%)
      was severely disabled, and 5 (55.6%) were moderately disabled. CONCLUSIONS:
      Isolated venous thrombosis of the posterior fossa is infrequent and implies a
      challenging diagnosis. Risk factors for intracranial vein thrombosis and atypical
      cerebellar findings on CT should lead to further MRI assessment.

PMID- 20798373
TI  - High von Willebrand factor levels increase the risk of stroke: the Rotterdam
      study.
AB  - BACKGROUND AND PURPOSE: Many studies have investigated the role of plasma von
      Willebrand factor level in coronary heart disease, but few have investigated its
      role in stroke. The aim of this study was to determine if von Willebrand factor
      levels are associated with the risk of stroke. METHODS: The study was part of the
      Rotterdam Study, a large population-based cohort study among subjects aged >=55
      years. We included 6 250 participants who were free from stroke at baseline (1997
      to 2001) and for whom blood samples were available. Follow-up for incident stroke
      was complete up to January 1, 2005. Data were analyzed with Cox proportional
      hazards models adjusted for age and sex and additionally with models adjusted for
      other potential confounders including ABO blood group. A subgroup analysis was
      performed in participants without atrial fibrillation. Effect modification by sex
      was tested on a multiplicative and on an additive scale. RESULTS: During an
      average follow-up time of 5.0 years, 290 first-ever strokes occurred, of which
      197 were classified as ischemic. The risk of stroke increased with increasing von
      Willebrand factor levels (age- and sex-adjusted hazard ratios per SD increase in
      von Willebrand factor level: 1.12 [95% CI, 1.01 to 1.25] for stroke, 1.13 [95%
      CI, 0.99 to 1.29] for ischemic stroke). Adjustments for additional confounders
      slightly attenuated the association. The association was also present in subjects
      without atrial fibrillation and did not differ between sexes. CONCLUSIONS: High
      von Willebrand factor levels are associated with stroke risk in the general
      population.

PMID- 20798375
TI  - Optimizing stroke clinical trial design: estimating the proportion of eligible
      patients.
AB  - BACKGROUND AND PURPOSE: Clinical trial planning and site selection require an
      accurate estimate of the number of eligible patients at each site. In this study,
      we developed a tool to calculate the proportion of patients who would meet a
      specific trial's age, baseline severity, and time to treatment inclusion
      criteria. METHODS: From a sample of 1322 consecutive patients with acute ischemic
      cerebrovascular syndromes, we developed regression curves relating the proportion
      of patients within each range of the 3 variables. We used half the patients to
      develop the model and the other half to validate it by comparing predicted vs
      actual proportions who met the criteria for 4 current stroke trials. RESULTS: The
      predicted proportion of patients meeting inclusion criteria ranged from 6% to 28%
      among the different trials. The proportion of trial-eligible patients predicted
      from the first half of the data were within 0.4% to 1.4% of the actual proportion
      of eligible patients. This proportion increased logarithmically with National
      Institutes of Health Stroke Scale score and time from onset; lowering the
      baseline limits of the National Institutes of Health Stroke Scale score and
      extending the treatment window would have the greatest impact on the proportion
      of patients eligible for a stroke trial. CONCLUSIONS: This model helps estimate
      the proportion of stroke patients eligible for a study based on different upper
      and lower limits for age, stroke severity, and time to treatment, and it may be a
      useful tool in clinical trial planning.

PMID- 20798374
TI  - Association between human immunodeficiency virus infection and stiffness of the
      common carotid artery.
AB  - BACKGROUND AND PURPOSE: Individuals with human immunodeficiency virus (HIV) who
      use highly active antiretroviral therapy (HAART) may have an increased risk for
      cardiovascular-related events, although the underlying mechanism remains unclear.
      We tested the hypothesis that carotid arterial stiffness was higher among persons
      using HAART compared to HAART-naive and HIV-uninfected persons. METHODS: Between
      2004 and 2006, we performed high-resolution B-mode ultrasound on 2789 HIV
      infected and HIV-uninfected participants of the Women's Interagency HIV Study
      (1865 women) and the Multicenter AIDS Cohort Study (924 men) and determined
      carotid arterial distensibility, which is a direct measure of carotid arterial
      stiffness. We used generalized estimating equations to evaluate the association
      between distensibility and HIV infection, CD4(+) cell count, and exposure to
      HAART adjusted for demographic, behavioral, and clinical characteristics.
      RESULTS: In multivariable analysis, distensibility was 4.3% lower (95% confidence
      interval, -7.4% to -1.1%) among HIV-infected vs uninfected participants. Among
      HIV-infected participants with <200 CD4(+) cells, distensibility was 10.5% lower
      (95% confidence interval, -14.5% to -6.2%) than that among HIV-uninfected
      participants, and this effect did not differ significantly by cohort or race.
      Concurrent HAART use was independently associated with lower distensibility among
      Multicenter AIDS Cohort Study participants but not among Women's Interagency HIV
      Study participants. CONCLUSIONS: Our finding that advanced HIV-related
      immunosuppression was associated with increased carotid arterial stiffness
      independent from the effects of traditional atherosclerosis risk factors suggests
      that the etiologic mechanism underlying reports of an increased cardiovascular
      disease risk among HIV-infected individuals might involve HIV-related
      immunosuppression leading to vascular dysfunction and arterial stiffening.

PMID- 20798376
TI  - ATP-binding cassette transporter G1 and high-density lipoprotein promote
      endothelial NO synthesis through a decrease in the interaction of caveolin-1 and
      endothelial NO synthase.
AB  - OBJECTIVE: To investigate whether cholesterol efflux to high-density lipoprotein
      (HDL) via ATP-binding cassette transporter G1 (ABCG1) modulates the interaction
      of caveolin (Cav) 1 and endothelial NO synthase (eNOS). METHODS AND RESULTS:
      ABCG1 promotes cholesterol and 7-oxysterol efflux from endothelial cells (ECs) to
      HDL. It was previously reported that ABCG1 protects against dietary cholesterol
      induced endothelial dysfunction by promoting the efflux of 7-oxysterols to HDL.
      Increased cholesterol loading in ECs is known to cause an inhibitory interaction
      between Cav-1 and eNOS and impaired NO release. In human aortic ECs, free
      cholesterol loading promoted the interaction of Cav-1 with eNOS, reducing eNOS
      activity. These effects of cholesterol loading were reversed by HDL in an ABCG1
      dependent manner. HDL also reversed the inhibition of eNOS by cholesterol loading
      in murine lung ECs, but this effect of HDL was abolished in Cav-1-deficient
      murine lung ECs. Increased interaction of Cav-1 with eNOS was also detected in
      aortic homogenates of high-cholesterol diet-fed Abcg1(-/-) mice, paralleling a
      decrease in eNOS activity and impaired endothelial function. CONCLUSIONS: The
      promotion of cholesterol efflux via ABCG1 results in a reduced inhibitory
      interaction of eNOS with Cav-1.

PMID- 20798377
TI  - The risk of deep venous thrombosis associated with injectable depot
      medroxyprogesterone acetate contraceptives or a levonorgestrel intrauterine
      device.
AB  - OBJECTIVE: To assess the risk of venous thrombosis associated with nonoral
      contraceptives (ie, injectable depot-medroxyprogesterone acetate contraceptives,
      hormone [levonorgestrel]-releasing intrauterine devices, a contraceptive patch,
      or a contraceptive implant). METHODS AND RESULTS: Analyses were performed in the
      Multiple Environmental and Genetic Assessment study, a large case-control study
      on risk factors for venous thrombosis. For the current analyses, we selected
      premenopausal women, aged 18 to 50 years, who were not pregnant nor within 4
      weeks postpartum and were not using oral contraceptives; 446 patients and 1146
      controls were included. Injectable depot-medroxyprogesterone acetate
      contraceptives were associated with a 3.6-fold (95% CI, 1.8- to 7.1-fold)
      increased risk of venous thrombosis compared with nonusers of hormonal
      contraceptives. The use of a levonorgestrel intrauterine device was not
      associated with an increased risk (odds ratio, 0.3; 95% CI, 0.1 to 1.1).
      Unfortunately, the few women using a contraceptive patch or an implant prevented
      a reliable estimate of the risk of thrombosis. CONCLUSIONS: The risk of venous
      thrombosis was increased for injectable depot-medroxyprogesterone acetate
      contraceptive users, while we were able to reliably exclude an increased risk
      associated with levonorgestrel intrauterine device use. Therefore, the latter
      seems to be the safest option regarding the risk of venous thrombosis.

PMID- 20798378
TI  - The emerging role of the thioredoxin system in angiogenesis.
AB  - Although there have been a multitude of studies, the mechanisms of angiogenesis
      remain incompletely understood. Increasing evidence suggests that cellular redox
      homeostasis is an important regulator of angiogenesis. The thioredoxin (TRX)
      system functions as an endogenous antioxidant that can exert influence over
      endothelial cell function via modulation of cellular redox status. It has become
      apparent that the cytosolic TRX1 isoform participates in both canonical and novel
      angiogenic signaling pathways and may represent an avenue for therapeutic
      exploitation. Recent studies have further identified a role for the mitochondrial
      isoform TRX2 in ischemia-induced angiogenesis. TRX-interacting protein (TXNIP) is
      the endogenous inhibitor of TRX redox activity that has been implicated in growth
      factor-mediated angiogenesis. As TXNIP is strongly induced by glucose, this
      molecule could be of consequence to disordered angiogenesis manifest in diabetes
      mellitus. This review will focus on data implicating the TRX system in
      endothelial cell homeostasis and angiogenesis.

PMID- 20798380
TI  - Relations of biomarkers of extracellular matrix remodeling to incident
      cardiovascular events and mortality.
AB  - OBJECTIVE: To evaluate if biomarkers reflecting left ventricular/vascular
      extracellular matrix remodeling are associated with cardiovascular disease (CVD)
      and death in the community. METHODS AND RESULTS: In 922 Framingham Study
      participants (mean age, 58 years; 56% women), we related circulating
      concentrations of matrix metalloproteinase-9 (binary variable: detectable versus
      undetectable), log of tissue inhibitor of matrix metalloproteinase-1, and log of
      procollagen type III aminoterminal peptide (PIIINP) to incident CVD and death. On
      follow-up (mean, 9.9 years), 51 deaths and 81 CVD events occurred. Each SD
      increment of log of tissue inhibitor of matrix metalloproteinase-1 and log-PIIINP
      was associated with multivariable-adjusted hazards ratios of 1.72 (95% CI, 1.30
      to 2.27) and 1.47 (95% CI, 1.11 to 1.96), respectively, for mortality risk. Log
      PIIINP concentrations were also associated with CVD risk (hazard ratio [95% CI]
      per SD, 1.35 [1.05 to 1.74]). Death and CVD incidence rates were 2-fold higher in
      participants with both biomarkers higher than the median (corresponding hazard
      ratio [95% CI], 2.78 [1.43 to 5.40] and 1.77 [1.04 to 3.03], respectively)
      compared with those with either or both less than the median. The inclusion of
      both biomarkers improved the C-statistic (for predicting mortality) from 0.78 to
      0.82 (P=0.03). Matrix metalloproteinase-9 was unrelated to either outcome.
      CONCLUSIONS: Higher circulating tissue inhibitor of matrix metalloproteinase-1
      and PIIINP concentrations are associated with mortality, and higher PIIINP is
      associated with incident CVD, in the community.

PMID- 20798379
TI  - Cardiovascular pathology in Hutchinson-Gilford progeria: correlation with the
      vascular pathology of aging.
AB  - OBJECTIVE: Children with Hutchinson-Gilford progeria syndrome (HGPS) exhibit
      dramatically accelerated cardiovascular disease (CVD), causing death from
      myocardial infarction or stroke between the ages of 7 and 20 years. We undertook
      the first histological comparative evaluation between genetically confirmed HGPS
      and the CVD of aging. METHODS AND RESULTS: We present structural and
      immunohistological analysis of cardiovascular tissues from 2 children with HGPS
      who died of myocardial infarction. Both had features classically associated with
      the atherosclerosis of aging, as well as arteriolosclerosis of small vessels. In
      addition, vessels exhibited prominent adventitial fibrosis, a previously
      undescribed feature of HGPS. Importantly, although progerin was detected at
      higher rates in the HGPS coronary arteries, it was also present in non-HGPS
      individuals. Between the ages of 1 month and 97 years, progerin staining
      increased an average of 3.34% per year (P<0.0001) in coronary arteries.
      CONCLUSIONS: We find concordance among many aspects of cardiovascular pathology
      in both HGPS and geriatric patients. HGPS generates a more prominent adventitial
      fibrosis than typical CVD. Vascular progerin generation in young non-HGPS
      individuals, which significantly increases throughout life, strongly suggests
      that progerin has a role in cardiovascular aging of the general population.

PMID- 20798382
TI  - SCH 602539, a protease-activated receptor-1 antagonist, inhibits thrombosis alone
      and in combination with cangrelor in a Folts model of arterial thrombosis in
      cynomolgus monkeys.
AB  - OBJECTIVE: To determine the antithrombotic effects of SCH 602539, an analog of
      the selective protease-activated receptor (PAR)-1 antagonist vorapaxar (formerly
      SCH 530348) currently in advanced clinical development, and the P2Y(12) ADP
      receptor antagonist cangrelor, alone and in combination. METHODS AND RESULTS:
      Multiple platelet activation pathways contribute to thrombosis. The effects of
      SCH 602539 and cangrelor alone and in combination on cyclic flow reductions were
      evaluated in a Folts model of thrombosis in cynomolgus monkeys. The effects of
      these treatments on ex vivo platelet aggregation and coagulation parameters were
      also monitored. Dose-dependent inhibition of cyclic flow reductions was observed
      after treatment with SCH 602539 alone and cangrelor alone (P<0.05 versus vehicle
      for the 2 highest concentrations of each agent). The combination of SCH 602539
      and cangrelor was associated with synergistic antithrombotic effects (P<0.05
      versus vehicle for all combinations tested). The 2 highest doses of SCH 602539
      inhibited platelet aggregation in response to PAR-1-selective high-affinity
      thrombin receptor agonist peptide by greater than 80% but did not affect platelet
      aggregation induced by other agonists; also, they did not affect any coagulation
      parameters. CONCLUSIONS: The combined inhibition of the PAR-1 and the P2Y(12) ADP
      platelet activation pathways had synergistic antithrombotic and antiplatelet
      effects. The addition of a PAR-1 antagonist to a P2Y(12) ADP receptor antagonist
      may provide incremental clinical benefits in patients with atherothrombotic
      disease, both in short- and long-term settings. These hypotheses need to be
      tested clinically.

PMID- 20798381
TI  - Human umbilical cord blood-derived endothelial cells reendothelialize vein grafts
      and prevent thrombosis.
AB  - OBJECTIVE: To accelerate vein graft reendothelialization and reduce vein graft
      thrombosis by infusing human umbilical cord blood-derived endothelial cells (hCB
      ECs) because loss of endothelium contributes to vein graft thrombosis and
      neointimal hyperplasia. METHODS AND RESULTS: Under steady flow conditions in
      vitro, hCB-ECs adhered to smooth muscle cells 2.5 to 13 times more than ECs
      derived from peripheral blood or human aorta (P<0.05). Compared with peripheral
      blood and human aorta ECs, hCB-ECs had 1.4-fold more cell surface alpha(5)beta(1)
      integrin heterodimers per cell (P<0.05) and proliferated on fibronectin 4- to 10
      fold more rapidly (P<0.05). Therefore, we used hCB-ECs to enhance
      reendothelialization of carotid interposition vein grafts implanted in NOD.CB17
      Prkdc(scid)/J mice. Two weeks postoperatively, vein grafts from hCB-EC-treated
      mice demonstrated approximately 55% reendothelialization and no luminal
      thrombosis. In contrast, vein grafts from sham-treated mice demonstrated luminal
      thrombosis in 75% of specimens (P<0.05) and only approximately 14%
      reendothelialization. In vein grafts from hCB-EC-treated mice, 33+/-10% of the
      endothelium was of human origin, as judged by human major histocompatibility
      class I expression. CONCLUSIONS: The hCB-ECs adhere to smooth muscle cells under
      flow conditions in vitro, accelerate vein graft reendothelialization in vivo, and
      prevent vein graft thrombosis. Thus, hCB-ECs offer novel therapeutic
      possibilities for vein graft disease.

PMID- 20798384
TI  - Castration- and aging-induced changes in the expression of zinc transporter and
      metallothionein in rat prostate.
AB  - Prostate tissue contains high concentrations of zinc. Zinc content in the
      prostate gland changes in prostatic disease, such as benign prostate hyperplasia
      and prostate cancer, which occur more frequently with increasing age. Prostate
      zinc content is also known to decrease after castration in animal models. It is
      not clear how prostate zinc content is regulated; therefore, to clarify the
      mechanisms underlying zinc homeostasis, we examined zinc content and the
      expression of zinc transporters and metallothioneins in the prostates of aged or
      castrated rats. Zinc concentration was measured by flame atomic absorption
      spectrometry. The mRNA expression of zinc transporters and metallothioneins was
      determined by real-time reverse transcriptase polymerase chain reaction analysis.
      The expression of the zinc transporter Slc30a2 (Znt2) in ventral prostate (VP) of
      aged rats (21 months) was approximately 21-fold higher than that in VP of young
      rats (4 months), and zinc levels in VP of young rats increased significantly
      compared with that in aged rats. Zinc content in lateral prostate (LP) and dorsal
      prostate did not differ between young and aged rats. Decreased metallothionein-3
      (Mt3) expression was observed in LP of castrated rats, and this reduction was
      prevented by testosterone replacement. Zinc content and Mt3 expression levels
      correlated significantly in rat LP. Our findings suggest that Mt3 could play a
      critical role in zinc homeostasis in rat LP.

PMID- 20798385
TI  - Increased risk of benign prostatic enlargement among patients with liver
      cirrhosis: a nationwide population-based study.
AB  - There have been several post mortem studies focusing on the association between
      liver cirrhosis and benign prostate hyperplasia; however, the results are
      controversial. The aim of this study was to estimate the risk of benign prostatic
      enlargement during a 5-year follow-up period following a liver cirrhosis
      diagnosis, using nationwide population-based data and a retrospective cohort
      design. We used the "Longitudinal Health Insurance Database," derived from the
      Taiwan National Health Insurance program. The study cohort comprised 661 patients
      who had received treatment for liver cirrhosis between 1997 and 2001; the
      comparison cohort was composed of 3305 randomly selected patients. Stratified Cox
      proportional hazard regressions were performed as a means of comparing the 5-year
      benign prostatic enlargement survival rate for the 2 cohorts. Of the sampled
      patients, 808 patients (20.4%) developed benign prostatic enlargement during the
      follow-up period (ie, 163 individuals from the study cohort [24.7% of the
      patients with liver cirrhosis] and 645 individuals from the comparison cohort
      [19.5% of comparison cohort patients]). The log-rank test indicated that patients
      with liver cirrhosis had significantly lower 5-year benign prostatic enlargement
      free survival rates than the controls (P < .001). The adjusted hazard ratios for
      benign prostatic enlargement following diagnosis with liver cirrhosis were 1.41
      during the 5-year follow-up period. We conclude that the risk for benign
      prostatic enlargement increased after a diagnosis of liver cirrhosis. Further
      studies are needed to identify the underlying pathophysiology.

PMID- 20798387
TI  - Pregnancy rate after varicocele repair: how many miscarriages?

PMID- 20798388
TI  - Developmental expression of SRC-related tyrosine kinases in the mouse testis.
AB  - An increase in protein tyrosine phosphorylation occurs during sperm capacitation
      in numerous species. The involvement of Src-related tyrosine kinases in this
      phenomenon has been demonstrated using different inhibitors specifically
      targeting this family of enzymes. In mammals, this group of nonreceptor tyrosine
      kinases is made up of 8 members with similar SRC homology domain 3 (SH3) and SH2
      domains. Although some members of this group of enzymes can compensate for one
      another, showing some redundancy, each is unique and may perform specific
      functions during male germ cell development. To further characterize the
      importance of Src-related tyrosine kinases in the events leading to proper sperm
      formation, and because no inhibitor affecting a single gene product exists,
      expression of Src, Yes1, Fyn, Lyn, Lck, Hck, Blk, and Fgr was assessed by real
      time polymerase chain reaction in developing mouse testes and in enriched
      populations of mouse spermatogenic cells, revealing distinct expression profiles
      for each kinase during testis development and in isolated male germ cells.
      Immunolocalization of SRC, LYN, and HCK in adult mouse testes as well as in
      mature spermatozoa further confirmed differential localization of these kinases
      during spermatogenesis. Although mRNA levels of these latter kinases were higher
      in spermatogonia and spermatocytes than in spermatids, protein levels were
      highest in spermatids, suggesting delayed transcript translation. Taken together,
      these results clearly show an uneven expression of each kinase in different
      spermatogenic cells, indicating that each member may play a different role during
      spermatogenesis, in addition to highlighting the complexity of Src-related kinase
      expression regulation in male germ cells. Furthermore, differential localization
      of these tyrosine kinases in mature spermatozoa also suggests a specific role for
      each member in sperm function and integrity.

PMID- 20798386
TI  - High-dose isoflavones do not improve metabolic and inflammatory parameters in
      androgen-deprived men with prostate cancer.
AB  - The profound hypogonadism that occurs with androgen deprivation therapy (ADT) for
      prostate cancer (PCa) results in complications such as diabetes and metabolic
      syndrome that predispose to cardiovascular disease. Because phytoestrogens have
      been associated with an improvement in metabolic parameters, we evaluated their
      role in men undergoing ADT. Our objective was to evaluate the effects of high
      dose isoflavones on metabolic and inflammatory parameters in men undergoing ADT.
      This was a randomized, double-blind, placebo-controlled, 12-week pilot study.
      Participants were randomly assigned to receive 20 g of soy protein containing 160
      mg of total isoflavones vs taste-matched placebo (20 g whole milk protein). The
      study was conducted at a tertiary care center in the United States. Thirty-three
      men (isoflavones = 17, placebo = 16) undergoing ADT for PCa completed this pilot
      study. Mean age in the 2 groups was 69 years and the majority of men were
      Caucasians. Mean duration of ADT in both groups was approximately 2 years (P =
      .70). The 2 groups were well matched at baseline. After 12 weeks of intervention,
      there was no significant difference in either metabolic or inflammatory
      parameters between the 2 groups. We found that high-dose isoflavones over a
      course of 12 weeks do not improve metabolic or inflammatory parameters in
      androgen-deprived men.

PMID- 20798389
TI  - Long-term effects of dimethandrolone 17beta-undecanoate and 11beta-methyl-19
      nortestosterone 17beta-dodecylcarbonate on body composition, bone mineral
      density, serum gonadotropins, and androgenic/anabolic activity in castrated male
      rats.
AB  - The potent androgens dimethandrolone 17beta-undecanoate (DMAU) and 11beta-methyl
      19-nortestosterone 17beta-dodecylcarbonate (11beta-MNTDC) are in development for
      androgen replacement therapy and hormonal contraception in men. They can be
      delivered either orally or as long-acting injectables. In the current study,
      their long-term effects on body composition (percentage lean and fat mass); bone
      mineral density (BMD); serum gonadotropin levels; and weights of the prostate,
      seminal vesicles, and levator ani muscle were assessed. Four-week-old male rats
      were sham-operated (intact) or castrated (Cx) and treated subcutaneously for 16
      weeks postsurgery with vehicle (Cx, intact), DMAU, or 11beta-MNTDC every 4 weeks;
      testosterone enanthate (TE) every 2 weeks; or a testosterone (T) implant. There
      were significant differences in body weights over time with a general trend of
      intact = Cx + T = Cx + TE > Cx + 11beta-MNTDC > Cx > Cx + DMAU. At week 18, rats
      were evaluated by dual-energy x-ray absorptiometry using the whole-body function
      of the Hologic software. The percentage lean body mass and BMD were lower (P <
      .05) in Cx rats than intact rats but equivalent in all groups of androgen-treated
      Cx rats and intact rats (P > .05). The highest percentage body fat was observed
      in Cx rats. Only DMAU- and 11beta-MNTDC-treated rats had lower percentage body
      fat compared with Cx rats (P < .05). Prostate, seminal vesicles, and levator ani
      muscle weights, corrected for final body weight, were decreased (P < .05) in Cx
      compared with intact rats and increased to varying extents in androgen-treated Cx
      rats compared with Cx rats (P < .05). The most marked increases were observed in
      the DMAU-treated rats in which prostate and seminal vesicle weights/kg body
      weight were 2.4 to 2.7 times those of intact rats, and levator ani muscle weights
      were increased approximately 1.5-fold. Blood was collected from the tail vein at
      weeks 4, 8, 12, and 16 for measurement of serum levels of androgens and at
      necropsy at week 18 for measurement of serum gonadotropins. Serum levels of
      luteinizing hormone and follicle-stimulating hormone were greatly elevated in Cx
      rats at week 18 and suppressed to levels comparable to those in intact rats by
      DMAU, 11beta-MNTDC, and T implants (P > .05). Collectively, our data indicate
      that androgen replacement with DMAU or 11beta-MNTDC in Cx rats resulted in
      favorable changes in body composition and maintenance of BMD comparable to those
      of T.

PMID- 20798390
TI  - How to detect Chlamydia trachomatis in males?
AB  - Much is known about the role of Chlamydia trachomatis in female infertility,
      although the same cannot be said about the organism's role in male infertility.
      Recently a number of researchers have provided a possible explanation of the
      pathogenesis of C trachomatis in male infertility and have suggested further
      studies. Unfortunately, current screening recommendations for C trachomatis in an
      infertile couple are vague and unhelpful, and many do not even mention this type
      of screening in the male. To enable any progress to be made in this field, it is
      essential that investigators know how best to detect C trachomatis, especially in
      the male. It is important, therefore, to know which specimen is best for C
      trachomatis detection, with respective strengths and weaknesses of each specimen.
      Similarly, it is equally important to have knowledge of which test is appropriate
      for the type of specimen being examined. First void urine is currently the
      specimen of choice for the routine detection of C trachomatis in males. Moreover,
      the best detection protocols in the developed world are based on molecular
      diagnosis of first void urine. These methods provide the best combination of
      sensitivity and specificity that is currently available on a clinical sample that
      can be self-taken. Interestingly, because semen is routinely collected for
      analysis in men of infertile couples, it has been suggested that protocols be
      developed for the optimal detection of C trachomatis in this specimen. Semen
      might provide additional information on infection of the upper genital tract,
      which may not be detected in first void urine. Finally, the importance of
      comparing tests for C trachomatis detection in updating our knowledge has been
      highlighted by the inability of some molecular methods to detect the new variant
      strain of C trachomatis.

PMID- 20798391
TI  - Expression of luteinizing hormone receptors in the mouse penis.
AB  - The role of luteinizing hormone (LH) in the regulation of normal reproductive
      functions in males and females is quite well established. Besides the expression
      of LH receptors in the target cells in gonads, it has been found in several
      extragonadal organs. There is no information about the expression of LH receptors
      in the penis up to now. The aim of the present study is to investigate the
      expression of the LH receptor in the mouse penis to see if LH effects are
      possible in the penis. BALB/c mice were used as donors of normal penis and testis
      tissue. Immunocytochemistry, Western blotting, and quantitative reverse
      transcriptase polymerase chain reactions (RT-PCRs) were used for the detection of
      the LH receptor. Positive immunoreaction for LH receptors was present in the
      nuclei of urethral epithelium and endothelial cells of cavernous spaces in the
      corpus cavernosum and corpus spongiosum penis. Western blotting experiments
      demonstrated the presence of LH antigen at M(r) = 97.4 and 78 kd. Quantitative RT
      PCRs confirmed the expression of LH receptor in the penis. Our results show that
      LH receptor is expressed in the body of the mouse penis; thus, it may directly
      regulate functions of penile tissue.

PMID- 20798392
TI  - Age-dependent chromosomal distribution of male-biased genes in Drosophila.
AB  - We investigated the correlation between the chromosomal location and age
      distribution of new male-biased genes formed by duplications via DNA
      intermediates (DNA-level) or by de novo origination in Drosophila. Our genome
      wide analysis revealed an excess of young X-linked male-biased genes. The
      proportion of X-linked male-biased genes then diminishes through time, leading to
      an autosomal excess of male-biased genes. The switch between X-linked and
      autosomal enrichment of male-biased genes was also present in the distribution of
      both protein-coding genes on the D. pseudoobscura neo-X chromosome and microRNA
      genes of D. melanogaster. These observations revealed that the evolution of male
      biased genes is more complicated than the previously detected one-step X->A gene
      traffic and the enrichment of the male-biased genes on autosomes. The pattern we
      detected suggests that the interaction of various evolutionary forces such as the
      meiotic sex chromosome inactivation (MSCI), faster-X effect, and sexual
      antagonism in the male germline might have shaped the chromosomal distribution of
      male-biased genes on different evolutionary time scales.

PMID- 20798393
TI  - Ornithine decarboxylase-1 polymorphism, chemoprevention with eflornithine and
      sulindac, and outcomes among colorectal adenoma patients.
AB  - The ornithine decarboxylase-1 (ODC1) polymorphism at position +316 affects
      binding by transcriptional activators and repressors and modulates the risk of
      metachronous colorectal adenomas, particularly in association with aspirin use.
      We investigated the effects of ODC1 after treatment with difluoromethylornithine
      (eflornithine)/sulindac or placebo. Two hundred twenty-eight colorectal adenoma
      patients in a randomized phase III trial were genotyped for ODC1. We used
      Wilcoxon rank sums tests on non-normally distributed continuous variables across
      two genotype groups, chi(2) or Fisher exact test to assess the association
      between baseline categorical variables and genotype group, and log binomial
      regression for the primary (adenoma recurrence) and secondary outcomes (tissue
      polyamine response, cardiovascular toxicity, gastrointestinal toxicity, and
      ototoxicity). All statistical tests were two-sided. In binomial regression models
      with variables age, sex, race, aspirin use, treatment, and ODC1 genotype,
      treatment was the only statistically significant factor associated with
      differences in adenoma recurrence or tissue polyamine response. A statistically
      significant interaction was detected between ODC1 genotype and treatment with
      respect to adenoma recurrence (placebo group: GG, 50%, AA/GA: 34%; treatment
      group: GG, 11%, AA/GA, 21%; P(interaction) = .038). Excess ototoxicity was
      observed among ODC1 AA patients receiving treatment, but the interaction of
      genotype and treatment on ototoxicity was not statistically significant (P =
      .45).

PMID- 20798395
TI  - Is non-invasive testing for sexually transmitted infections an efficient and
      acceptable alternative for patients? A randomised controlled trial.
AB  - OBJECTIVES: A randomised controlled trial was conducted to assess and quantify
      the efficacy and acceptability of non-invasive testing (NIT) for sexually
      transmitted infections (STI) in asymptomatic patients within a genitourinary
      medicine clinic. METHODS: Patients were randomly assigned to either standard of
      care (SOC-STI testing with genital examination) or NIT. The length of time
      patients spent in the clinic was recorded and patients were asked to complete a
      satisfaction survey. RESULTS: 391 participants were randomly assigned. The length
      of time male and female patients spent in the clinic was significantly shorter
      with NIT (men 26 min; women 23 min) compared with SOC (men 41 min; women 45 min,
      p<0.0001), but most of this decrease was due to reduced patient waiting time
      within the clinic, rather than less time spent with medical or nursing staff.
      Those randomly assigned to NIT were significantly more likely to state they were
      in clinic for less time than expected (p<0.01) and report that the tests were
      less uncomfortable than expected (p<=0.04). For both men and women, more patients
      in the SOC group declined testing for syphilis (14%) and HIV (20%) compared with
      NIT (7% and 13%, respectively), but this was only significantly different between
      treatments for female patients (p<=0.02). CONCLUSIONS: NIT for STI in
      asymptomatic patients can reduce the time patients spend in the clinic when
      combined with appropriate patient care pathways, and is an acceptable alternative
      to physician-taken genital swabs.

PMID- 20798394
TI  - Comprehensive analysis of phosphorylation sites in Tensin1 reveals regulation by
      p38MAPK.
AB  - Tensin1 is the archetype of a family of focal adhesion proteins. Tensin1 has a
      phosphotyrosine binding domain that binds the cytoplasmic tail of beta-integrin,
      a Src homology 2 domain that binds focal adhesion kinase, p130Cas, and the RhoGAP
      called deleted in liver cancer-1, a phosphatase and tensin homology domain that
      binds protein phosphatase-1alpha and other regions that bind F-actin. The
      association between tensin1 and these partners affects cell polarization,
      migration, and invasion. In this study we analyzed the phosphorylation of human S
      tag-tensin1 expressed in HEK293 cells by mass spectrometry. Peptides covering
      >90% of the sequence initially revealed 50 phosphorylated serine/phosphorylated
      threonine (pSer/pThr) but no phosphorylated tyrosine (pTyr) sites. Addition of
      peroxyvanadate to cells to inhibit protein tyrosine phosphatases exposed 10 pTyr
      sites and addition of calyculin A to cells to inhibit protein phosphatases type 1
      and 2A gave a total of 62 pSer/pThr sites. We also characterized two sites
      modified by O-linked N-acetylglucosamine. Tensin1 F302A, which does not bind
      protein phosphatase-1, showed > twofold enhanced phosphorylation of seven sites.
      The majority of pSer/pThr have adjacent proline (Pro) residues and we show
      endogenous p38 mitogen activated protein kinase (MAPK) associated with and
      phosphorylated tensin1 in an in vitro kinase assay. Recombinant p38alpha MAPK
      also phosphorylated S-tag-tensin1, resulting in decreased binding with deleted in
      liver cancer-1. Activation of p38 MAPK in cells by sorbitol-induced hyperosmotic
      stress increased phosphorylation of S-tag-tensin1, which reduced binding to
      deleted in liver cancer-1 and increased binding to endogenous pTyr proteins,
      including p130Cas and focal adhesion kinase. These data demonstrate that tensin1
      is extensively phosphorylated on Ser/Thr residues in cells and phosphorylation by
      p38 MAPK regulates the specificity of the tensin1 Src homology 2 domain for
      binding to different proteins. Tensin1 provides a hub for connecting signaling
      pathways involving p38 MAP kinase, tyrosine kinases and RhoGTPases.

PMID- 20798397
TI  - Pharyngeal gonorrhoea: a silent cause for concern.

PMID- 20798396
TI  - Ocular syphilis among HIV-infected patients: a systematic analysis of the
      literature.
AB  - BACKGROUND: Ocular syphilis among HIV-infected patients continues to be a problem
      in the highly active antiretroviral therapy (HAART) era. However, outside of case
      reports or small case series, little is known about the clinical, laboratory, and
      treatment outcomes of these patients. Objective To examine the literature on HIV
      infected patients and determine the results of treatment. METHODS: Systematic
      review of cases series and case reports among HIV-infected individuals with
      ocular syphilis. Reviews, languages other than English and pre-1980 reports were
      excluded. The effect of CD4 count and virological suppression on clinical
      manifestations and diagnostic laboratory values was evaluated. RESULTS: A total
      of 101 HIV-infected individuals in case series and case reports were identified.
      Ocular syphilis led to the HIV diagnosis in 52% of cases, including patients with
      CD4 count >200 cells/mm(3). Posterior uveitis was significantly more common in
      individuals with CD4 count <200 cells/mm(3) (p = 0.002). Three patients with
      confirmed ocular syphilis had negative non-treponemal tests. Ninety-seven per
      cent of patients with visual impairment improved following intravenous penicillin
      or ceftriaxone. CONCLUSIONS: Non-treponemal tests may be negative in HIV-infected
      patients with ocular syphilis. Ocular syphilis remains an important clinical
      manifestation that can lead to initial HIV diagnosis.

PMID- 20798398
TI  - When mental inflexibility facilitates executive control: beneficial side effects
      of ruminative tendencies on goal maintenance.
AB  - Although previous research suggests that depressive ruminators tend to become
      stuck in a particular mind-set, this mental inflexibility may not always be
      disadvantageous; in some cases, it may facilitate active maintenance of a single
      task goal in the face of distraction. To evaluate this hypothesis, we tested 98
      college students, who differed in ruminative tendencies and dysphoria levels, on
      two executive-control tasks. One task emphasized fast-paced shifting between
      goals (letter naming), and one emphasized active goal maintenance (modified
      Stroop). Higher ruminative tendencies predicted more errors on the goal-shifting
      task but fewer errors on the goal-maintenance task; these results demonstrated
      that ruminative tendencies have both detrimental and beneficial effects.
      Moreover, although ruminative tendencies and dysphoria levels were moderately
      correlated (r = .42), higher dysphoria levels predicted more errors on the goal
      maintenance task; this finding indicates that rumination and dysphoria can have
      opposing effects on executive control. Overall, these results suggest that
      depressive rumination reflects a trait associated with more stability (goal
      maintenance) than flexibility (goal shifting).

PMID- 20798399
TI  - Anti-inflammatory effect of maraviroc in an HIV-infected patient with concomitant
      myositis: a case report.
AB  - We report the surprising yet sought impact that an antiretroviral (ARV) regimen
      containing maraviroc had on an HIV-infected and heavily highly active
      antiretroviral therapy (HAART)-experienced patient with chronic polymyositis. The
      patient had elevated creatine kinase (CK) levels in serum for 6 years, reaching
      peaks over 900 U/L and showing only partial response to high-dose steroids, not
      responding to HAART withdrawal. The disease started while on second-line HAART
      and gradually impaired his muscular function, leading to the absolute loss of the
      ability to stand on his legs. Atherosclerosis and hypertension contributed to the
      development of myocardial infarction. The association of unboosted atazanavir
      (ATV) plus maraviroc was designed hoping in a protective role on the
      cardiovascular system and in an anti-inflammatory effect that some authors have
      hypothesized. After only 3 months the patient's CK levels had normalized and with
      the help of rehabilitation he recovered the ability to walk, which he still
      maintains at the one year of observation.

PMID- 20798400
TI  - Lung cancer in HIV-infected patients: the experience of an urban clinic.
AB  - BACKGROUND: Lung cancer is one of the most common non-AIDS-defining malignancies
      among HIV-infected patients. Recent studies suggest that lung cancer risk is 3 to
      4 times higher in HIV-infected patients than in uninfected persons after
      adjusting for other factors such as smoking intensity and duration. METHODS: A
      retrospective chart review (2002-2009) was conducted in our institution. An
      abstraction form was used to compile data that included demographics, T-cell
      count, and viral loads before and at the time of diagnosis, comordibities,
      smoking, and use of alcohol and drugs. RESULTS: A total of 16 patients were
      found. Of these, 11 (69%) patients were male and 5 (31%) female. The average age
      at diagnosis was 49 years (range 36-54). The Majority of patients were African
      American (90%). Their average CD4 counts before and at the time of diagnoses were
      241 and 211 cells/mm( 3), respectively. Their viral loads before and at the time
      of diagnosis ranged from <48 to 437 000 and <48 to 590 760 copies/mL,
      respectively. Adenocarcinoma was found in 67% of cases. The majority of cases
      (85%) were detected at advanced stages (IIIB or IV). Smoking was found in 100% of
      cases (average of 15-20 pack/year history), alcohol use in 70% of cases, and drug
      abuse in 50%. CONCLUSIONS: Lung cancer is very common in HIV-infected
      populations. It tends to occur at a young age, and it is usually diagnosed at
      very advanced stages (IIIB or IV). The main risk factors found in our study were
      extensive smoking history, young age, male sex, and potentially prolonged
      immunosuppression. Based on these results, an attempt to construct a high-risk
      group index might not be appropriate due to the limited number of cases studied
      and the need for further evaluation of the length of immunosuppression and the
      real impact of HIV RNA viral load in the development of lung cancer.

PMID- 20798402
TI  - Low prevalence of primary HIV resistance in western Massachusetts.
AB  - Most studies of primary antiretroviral (ARV) resistance have been conducted in
      large metropolitan areas with reported rates of 8% to 25%. We collected data on
      99 HIV-1-infected antiretroviral-naive patients from several sites in
      Springfield, MA, who underwent genotypic resistance assay between 2004 and 2008.
      Only major resistance mutations per International AIDS Society-USA (IAS-USA) drug
      resistance mutations list were considered. The prevalence of resistance was 5% (5
      of 99). Three patients had one nonnucleoside reverse transcriptase inhibitor
      (NNRTI) mutation: 103N, 103N, and 190A, 1 patient had a protease inhibitor (PI)
      mutation: 90M; and 1 patient had 3-class resistance with NNRTI: 181C, 190A, PI:
      90M, and nucleoside analogue reverse transcriptase inhibitor (NRTI): 41L, 210W.
      Mean time from HIV diagnosis to resistance testing was shorter in patients with
      resistance versus those without: 9 (range 0.3-42 months) versus 27 (range 0.1-418
      months), P = .11. There was a trend to lower mean CD4 count in those with
      resistance, 170 versus 318 cells/mm(3), P = .06. No differences were noted in
      gender, age, HIV risk category, or HIV RNA level. The low prevalence of primary
      resistance may be explained by differences in demographic and risk factors or may
      reflect the time from infection to resistance testing. Our findings emphasize the
      importance of continued resistance surveillance.

PMID- 20798401
TI  - Screening for hazardous alcohol use and depressive symptomatology among HIV
      infected patients in Nigeria: prevalence, predictors, and association with
      adherence.
AB  - Scores from the Alcohol Use Disorders Identification Test (AUDIT) and the Center
      for Epidemiological Studies Depression Scale (CES-D) administered to both
      antiretroviral therapy (ART)-experienced and -naive adults in HIV care in Nigeria
      were evaluated for association with participant characteristics and ART adherence
      measured by pharmacy records. Participants included 222 ART-experienced and 177
      ART-naive adults, of whom 47 (12%) had AUDIT >/=8, 29 (7%) an AUDIT >/=10, 52
      (13%) a CES-D >/=16, and 25 (6%) a CES-D >/=21. An elevated AUDIT score was more
      frequent among ART-naive and men, while disclosure of HIV status to others was
      associated with lower scores. An elevated CES-D score was more frequent among ART
      naive and those with lower educational level, while disclosure of HIV status and
      choosing to be interviewed in English rather than Hausa was associated with lower
      scores. An elevated CES-D score was associated with poor adherence.

PMID- 20798403
TI  - Severe peripheral neuropathy following HAART initiation in an HIV-infected
      patient with leprosy.
AB  - We report a case of peripheral neuropathy following highly active antiretroviral
      therapy (HAART) initiation in a patient coinfected with HIV and Mycobacterium
      leprae and review the literature on leprosy-associated immune reconstitution
      inflammatory syndrome (IRIS). Physicians in charge of HIV-infected patients
      originating from countries endemic for leprosy should be aware of this risk of
      leprosy-associated IRIS when starting HAART.

PMID- 20798404
TI  - Occurrence of stavudine-induced lactic acidosis in 3 members of an African
      family.
AB  - Fixed-dose combinations containing stavudine have played a critical role in the
      worldwide scale-up of antiretroviral therapy, but increasing concern exists
      regarding adverse events due to mitochondrial toxicity. We describe the first
      reported occurrence of lactic acidosis within a family of 3 HIV-infected
      individuals. This report is only the second of lactic acidosis affecting an
      African child. Further research is indicated to identify possible genetic and
      other risk factors underlying mitochondrial toxicity in African populations,
      especially among pediatric cohorts.

PMID- 20798406
TI  - Medical memorials in the Linnean binomial taxonomy.

PMID- 20798407
TI  - The portrait of Dr Edward Harrison MD (1766-1838).
AB  - The portrait of the London and Horncastle Physician Edward Harrison, painted and
      displayed in 1823, was editorially criticized by one of the medical journals of
      the time. After Harrison died the portrait remained in the family estate until
      1938, after which it was presented to the National Gallery of Ireland. The image
      of Dr Harrison had never been displayed in any of his medical writings, nor in
      any other medical historical works, until 2008. This paper provides some history
      of the criticism of the portrait, similar to the historical vignette of the
      portraiture of William Harvey and outlines the detective work to track down the
      location of the portrait.

PMID- 20798408
TI  - The Harveian Society of London.

PMID- 20798409
TI  - Establishing the Golitsyn Hospital: the contribution of Professor Efrem Osipovich
      Mukhin (1766-1850).
AB  - Golitsynsky Hospital is one of the oldest Moscow clinics founded by the Russian
      Aristocrat Count Golitsyn in 1802. A prominent Russian surgeon and Professor at
      Moscow University, Efrem Mukhin became the first senior medical doctor at this
      hospital and played a crucial role in its development. Six hundred and eighty
      eight operations were performed at Golitsynsky Hospital between 1802 and 1807
      including obstetric, gynaecological, eye and ear interventions. Mukhin performed
      444 operations himself. The hospital continued functioning when Napoleon's troops
      occupied Moscow in September 1812. The French surgeons D Larrey, Degenet and De
      la Fliz worked there during this period, assisted by their Russian pupils A
      Migachev and V Sherbakov.

PMID- 20798410
TI  - Alzheimer's disease.

PMID- 20798411
TI  - Gandhi and the 'struck-off' doctor, Thomas Richard Allinson (1858-1918).
AB  - Gandhi visited London on several occasions. During two of these visits, when he
      was a law student from 1888 and again in 1914, he met Thomas Richard Allinson, a
      controversial doctor whose name was erased from the Medical Register in 1892.
      While in London studying for the bar, Gandhi was influenced in his search for a
      suitable vegetarian diet by the writings and personal support of Allinson.
      Although disagreeing profoundly with Allinson's views on birth control, he spoke
      up in defence of his right to hold them--probably the first time Gandhi
      challenged authority and an occasion which shows him as a tongue-tied young man
      but even then having a personal moral code that gives insight into the character
      of the future Mahatma. On Gandhi's further visit to England in 1914 Allinson,
      although no longer on the Medical Register, treated Gandhi for pleurisy,
      apparently partially successfully when orthodox medicine had failed.

PMID- 20798412
TI  - John Warren (1753-1815): American surgeon, patriot and Harvard Medical School
      founder.
AB  - Dr John Warren was educated in the medical apprenticeship tradition of mid-18th
      century Boston, Massachusetts. As a surgeon in the American Continental Army he
      honed not only his surgical but also his teaching skills by providing continuing
      medical education to his colleagues in Boston's military hospital. Warren became
      a driving force in post-war Boston medicine. His organizational talents, zeal for
      science and vision for Massachusetts medicine led to the creation of Harvard
      Medical School.

PMID- 20798413
TI  - Etienne Stephane Tarnier (1828-1897).

PMID- 20798414
TI  - John Woodall's amputation saw.

PMID- 20798415
TI  - Sir Edward Mellanby (1884-1955) GBE KCB FRCP FRS: nutrition scientist and medical
      research mandarin.
AB  - Edward Mellanby used the experimental method to investigate medical problems. In
      1918, working at King's College for Women, London, he provided conclusive
      evidence that rickets is a dietary deficiency disease due to lack of a fat
      soluble vitamin [D]. In Sheffield he demonstrated that cereals, in an unbalanced
      diet, produced rickets due to the phytic acid content reducing the availability
      of calcium. Mellanby became Secretary of the Medical Research Council (1933-49)
      but continued his research by working at weekends. In the 1930s he campaigned for
      the results of nutritional research to be used for the benefit of public health.
      During World War II he acted as a scientific adviser to the War Cabinet and had a
      strong influence on the food policy which maintained successfully the nutrition
      of the population during the shipping blockade. Mellanby was a formidable person
      but with sagacity he promoted new research and guided the expansion of the
      organization.

PMID- 20798416
TI  - William Roentgen's (1845-1923) influence: contrasts and comparisons.
AB  - William Roentgen's discovery of X-rays in 1895 influenced two students from
      Manchester who first met in 1899. They developed an interest in radiology of the
      gastrointestinal tract through which they maintained a long association. Sir
      Arthur Hurst, after qualifying in Oxford in 1904, became a renowned physician at
      Guy's Hospital, London, and founder of what was to become the British Society of
      Gastroenterology. Dr Alfred Barclay qualified in Cambridge in 1904 and
      subsequently became the first Consultant Radiologist in Manchester and doyen of
      gastrointestinal radiology. He moved to Cambridge in 1928 to sustain the DMRE
      course. In 1937 he was invited to join the Nuffield Institute of Medical Research
      in Oxford at an age when many would have considered retiring. In 1939 Hurst also
      returned to Oxford where he taught at the medical school and consulted at the
      Radcliffe Infirmary, bringing his path and Barclay's together once more.

PMID- 20798417
TI  - Robert Thompson Leiper FRS (1881-1969).

PMID- 20798418
TI  - Behcet's disease.

PMID- 20798419
TI  - The curious death of Constantine Samuel Rafinesque (1783-1840): the case for the
      maidenhair fern.
AB  - Constantine Rafinesque, a French emigre to America in the early 19th century, was
      a forerunner of Charles Darwin and a zealous field naturalist who identified
      thousands of new species of plants and animals. His career was controversial in
      part because of his unfocused ambition to gain scientific recognition. In his
      later years he published in many areas apart from biology. His polymathic life
      ended in 1840 with his death (aged 57) from stomach cancer. In 1826 he had
      developed an illness he thought was consumption and which he believed was cured
      by a herbal mixture he devised. It may have contained one or more species of
      ferns related to one now known to induce human gastric carcinoma. Rafinesque's
      self-medication may have led to his death years later.

PMID- 20798420
TI  - John Dickinson MB (1832-63), Chikwawa, Malawi.

PMID- 20798421
TI  - Telemedicine services: from idea to implementation.

PMID- 20798422
TI  - Remote care nearby.
AB  - A telemedicine application has a better chance of being accepted if the users can
      easily handle it and if the application fulfils the clinical needs of both
      patients and professionals. This requires a methodology for development in which
      three key matters need to be dealt with: (1) clinical content; (2) design; and
      (3) outcome. Concerning the clinical content, telemedicine services for patients
      with chronic disorders that aim to increase their level of functioning need to
      monitor aspects of the patient's functioning and provide adequate feedback about
      this. Promising parameters of functioning are related to general physical
      activity and muscle activation patterns. Providing adequate feedback requires
      choices about the content of the information, the modality of the feedback and
      its timing. Unfortunately, research into effective feedback strategies is still
      in its infancy. Concerning the design it appears that the different stakeholders
      involved speak different languages, that there is a lack of knowledge about
      aspects related to acceptance and a lack of good methods to define user
      requirements. Scenario-based requirements analysis is a promising technique to
      overcome these barriers. Concerning the outcome, evaluation of telemedicine
      services in everyday clinical practice has been mainly directed at measurement of
      technical performance and user satisfaction. Large scale clinical evaluation
      studies with multiple end points are needed. This development methodology with
      its three aspects was used for a myofeedback-based teletreatment service. This
      showed that telemedicine applications can be developed that have the potential to
      make health care more effective, efficient and accessible.

PMID- 20798423
TI  - A scenario guideline for designing new teletreatments: a multidisciplinary
      approach.
AB  - Lack of user acceptance of telemedicine services is an important barrier to
      deployment and stresses the need for involving users, i.e. medical professionals.
      However, the involvement of users in the service development process of
      telemedicine services is difficult because of (a) the knowledge gap between the
      expertise of medical and technical experts; (b) the language gap, i.e. the use of
      different terminologies between the medical and the technical professions; and
      (c) the methodological gap in applying requirement methods to multidisciplinary
      scientific matters. We have developed a guideline in which the medical and
      technical domains meet. The guideline can be used to develop a scenario from
      which requirements can be elicited. In a retrospective analysis of a myofeedback
      based teletreatment service, the technically-oriented People-Activities-Context
      Technology (PACT) framework and medically-oriented principles of evidence-based
      medicine were incorporated into a guideline. The guideline was developed to
      construct the content of a scenario which describes the new teletreatment
      service. This allows the different stakeholders to come together and develop the
      service. Our approach provides an arena for different stakeholders to take part
      in the early stages of the design process. This should increase the chance of
      user acceptance and thus adoption of the service being developed.

PMID- 20798424
TI  - The myofeedback-based teletreatment system and its evaluation.
AB  - The myofeedback-based teletreatment system allows patients to receive tactile
      and/or visual feedback on muscle activity and muscle relaxation times. Health
      care professionals can analyse muscle activity and muscle relaxation times and
      provide guidance to the patient on the course of treatment. The system was
      evaluated in a small clinical trial. Qualitative data were obtained by interviews
      and visual inspection of graphical patient data during the trial. Quantitative
      data were based on post-trial data analysis. We used a revised version of the
      information systems success model to evaluate the teletreatment system, and
      focused on the success categories of system use and user satisfaction. The
      evaluation found good input data quality, system quality and information quality.
      Both system use and user satisfaction were good. Thus the teletreatment system
      appears suitable for small scale clinical deployment. However, the sensory
      components suffered from heavy use and embedded software problems which made them
      unreliable. Large scale deployment requires improvement in terms of durability
      and reliability of the system's sensors.

PMID- 20798425
TI  - The clinical effectiveness of a myofeedback-based teletreatment service in
      patients with non-specific neck and shoulder pain: a randomized controlled trial.
AB  - We investigated the effectiveness and efficiency of a four-week myofeedback-based
      teletreatment service in subjects with non-specific neck and shoulder pain.
      Subjects were recruited in Belgium, Germany and the Netherlands and randomly
      allocated to the intervention or conventional care. Subjects in the intervention
      group received four weeks of myofeedback training. Pain intensity and disability
      were evaluated by questionnaires at baseline, immediately after four weeks of
      treatment and at follow-up 3 months later. To investigate efficiency, the time
      investment of both therapists and patients were assessed. Seventy-one subjects
      were included in the study (36 in the intervention group and 35 in the
      conventional care group). Myofeedback-based teletreatment was at least as
      effective clinically as conventional care. Pain intensity and disability
      decreased after 4 weeks of treatment in both groups and part of the effect
      remained at 3 months' follow-up. The teletreatment also increased efficiency for
      therapists by almost 20% and patients experienced the benefits of less travel
      time and travel costs by remote consultation. Myofeedback-based teletreatment has
      the potential to ensure more efficient treatment for patients with non-specific
      neck and shoulder pain.

PMID- 20798426
TI  - Relation between patient satisfaction, compliance and the clinical benefit of a
      teletreatment application for chronic pain.
AB  - We investigated the ease of use and usefulness as a measure of patient
      satisfaction, compliance, clinical benefit and its mutual relationships
      concerning a teletreatment application for chronic pain. Fifty-two subjects with
      neck and shoulder pain received and completed a four-week myofeedback-based
      teletreatment intervention. Prior to the onset of the intervention (at baseline)
      and immediately after the intervention they were asked to fill in questionnaires
      to measure discrepancies (gap scores) between expectations and experiences with
      the ease of use and usefulness of the treatment, as well as pain intensity and
      pain disability. In addition, the actual use of the system (i.e. the volume of
      muscle activity data available on the server) was logged. The subjects reported a
      significantly higher score on ease of use after the intervention compared to
      baseline, suggesting that the equipment was easier to use than they expected.
      Compliance was associated with clinical benefit. There was no significant
      relation between patient satisfaction and compliance. Patient satisfaction is a
      key indicator of how well the telemedicine treatment met expectations and
      compliance is important because of its association with clinical outcomes.

PMID- 20798427
TI  - Clinical evaluation of a myofeedback-based teletreatment service applied in the
      workplace: a randomized controlled trial.
AB  - We evaluated the clinical effects of a myofeedback-based teletreatment service in
      terms of pain, pain-related disability and work ability. We also investigated the
      time investment/savings of this treatment with respect to conventional care.
      Sixty-five women with neck and shoulder pain at work participated in the study.
      Thirty-three took part in the teletreatment and 32 participated in a control
      group which continued with conventional care. Questionnaires were completed
      before the start of the intervention (baseline) and at initial follow-up (T0) and
      3 months (T3) after the intervention ended. A general linear model analysis for
      repeated measurements showed an improvement in terms of pain and work ability for
      both groups taken together, with no differences between them. Non-parametric
      tests showed an intervention effect in pain-related disability for both groups
      together and no differences between them when tested at baseline, T0 and T3. The
      time saved in relation to conventional care was mainly from reduced travel time,
      which was 41 min per teleconsultation. The teletreatment service allowed
      employees to take part in muscle relaxation training while performing their
      regular work. The clinical evaluation showed that the treatment was on par with
      conventional care, but without the effort and time loss associated with regular
      visits to the clinic. We conclude that the myofeedback-based teletreatment
      service has potential for addressing neck and shoulder symptoms at the workplace.

PMID- 20798428
TI  - Prognostic factors for the effect of a myofeedback-based teletreatment service.
AB  - We investigated the potential prognostic factors for clinically relevant
      improvements in pain intensity and pain-related disability after myofeedback
      based teletreatment. Sixty-five female computer users, 56 female patients with
      whiplash-associated disorders and 18 female patients with non-specific neck and
      shoulder pain participated in the study. They received myofeedback-based
      teletreatment or usual treatment. Questionnaires concerning prognostic factors,
      pain and disability were completed before the start of the intervention
      (baseline) and at follow-ups at the end of the intervention, and after 3 and 6
      months. Logistic regression analyses were performed in order to investigate
      prognostic factors for clinically relevant improvement. In the intervention
      group, improvement in pain intensity was predicted by baseline pain intensity.
      Baseline pain intensity and disability, and fear-avoidance and endurance related
      pain coping responses were prognostic factors for outcome in pain-related
      disability in this group. There were few differences between the intervention
      groups; fear-avoidance coping responses influenced the outcome after
      teletreatment only. Myofeedback-based teletreatment appears to be an useful
      telemedicine intervention, especially for participants with moderate to high
      levels of pain and disability, high perceived help/hopelessness, and those who
      tend to deal with their pain by avoiding social and physical activities.

PMID- 20798429
TI  - Deployment of e-health services - a business model engineering strategy.
AB  - We designed a business model for deploying a myofeedback-based teletreatment
      service. An iterative and combined qualitative and quantitative action design
      approach was used for developing the business model and the related value
      network. Insights from surveys, desk research, expert interviews, workshops and
      quantitative modelling were combined to produce the first business model and then
      to refine it in three design cycles. The business model engineering strategy
      provided important insights which led to an improved, more viable and feasible
      business model and related value network design. Based on this experience, we
      conclude that the process of early stage business model engineering reduces risk
      and produces substantial savings in costs and resources related to service
      deployment.

PMID- 20798430
TI  - The Frank Horan essay prize.

PMID- 20798431
TI  - Embracing the future.

PMID- 20798432
TI  - A review of the use of common antiplatelet agents in orthopaedic practice.
AB  - Antiplatelet agents are widely prescribed for the primary and secondary
      prevention of cardiovascular events. A common clinical problem facing orthopaedic
      and trauma surgeons is how to manage patients receiving these agents who require
      surgery, either electively or following trauma. The dilemma is to balance the
      risk of increased blood loss if the antiplatelet agents are continued peri
      operatively against the risk of coronary artery/stent thrombosis and/or other
      vascular event if the drugs are stopped. The traditional approach of stopping
      these medications up to two weeks before surgery appears to pose significant
      danger to patients and may require review. This paper covers the important
      aspects regarding the two most commonly prescribed antiplatelet agents, aspirin
      and clopidogrel.

PMID- 20798433
TI  - Statistical power in testing a hypothesis.
AB  - In comparing or assessing methods of treatment it is vital that the appropriate
      number of patients is selected in order to ensure that the conclusions drawn are
      statistically viable. This annotation describes the relevance of a statistical
      power analysis in the context of hypothesis testing to the determination of the
      optimal sample size of a study. The power of the test indicates how likely it is
      that the test will correctly produce a statistically significant result.

PMID- 20798434
TI  - Translation of science to surgery: linking emerging concepts in biological
      cartilage repair to surgical intervention.
AB  - Orthopaedic surgery is in an exciting transitional period as modern surgical
      interventions, implants and scientific developments are providing new therapeutic
      options. As advances in basic science and technology improve our understanding of
      the pathology and repair of musculoskeletal tissue, traditional operations may be
      replaced by newer, less invasive procedures which are more appropriately targeted
      at the underlying pathophysiology. However, evidence-based practice will remain a
      basic requirement of care. Orthopaedic surgeons can and should remain at the
      forefront of the development of novel therapeutic interventions and their
      application. Progression of the potential of bench research into an improved
      array of orthopaedic treatments in an effective yet safe manner will require the
      development of a subgroup of specialists with extended training in research to
      play an important role in bridging the gap between laboratory science and
      clinical practice. International regulations regarding the introduction of new
      biological treatments will place an additional burden on the mechanisms of this
      translational process, and orthopaedic surgeons who are trained in science,
      surgery and the regulatory environment will be essential. Training and supporting
      individuals with these skills requires special consideration and discussion by
      the orthopaedic community. In this paper we review some traditional approaches to
      the integration of orthopaedic science and surgery, the therapeutic potential of
      current regenerative biomedical science for cartilage repair and ways in which we
      may develop surgeons with the skills required to translate scientific discovery
      into effective and properly assessed orthopaedic treatments.

PMID- 20798435
TI  - The plain beta-angle measured on radiographs in the assessment of
      femoroacetabular impingement.
AB  - The beta-angle is a radiological tool for measuring the distance between the
      pathological head-neck junction and the acetabular rim with the hip in 90 degrees
      of flexion in patients with femoroacetabular impingement. Initially it was
      measured using an open-chamber MRI. We have developed a technique to measure this
      angle on plain radiographs. Correlation analysis was undertaken to determine the
      relationship between the range of movement and the beta-angle in 50 patients with
      femoroacetabular impingement and 50 asymptomatic control subjects. Inter- and
      intra-observer reliability of the beta-angle was also evaluated. Patients with
      femoroacetabular impingement had a significantly smaller (p < 0.001) mean beta
      angle (15.6 degrees, 95% confidence interval (CI) 13.3 to 17.7) compared with the
      asymptomatic group (38.7 degrees, 95% CI 36.5 to 41.0). Correlation between
      internal rotation and the beta-angle was high in the impingement group and
      moderate in the asymptomatic group. The beta-angle had excellent inter- and intra
      observer reliability in both groups. Our findings suggest that the measurement of
      the beta-angle on plain radiography may represent a valid, reproducible and cost
      effective alternative to open MRI in the assessment of the pathological bony
      anatomy in patients with cam, pincer and mixed femoroacetabular impingement.

PMID- 20798436
TI  - Photographic measurement of the inclination of the acetabular component in total
      hip replacement using the posterior approach.
AB  - The angle of inclination of the acetabular component in total hip replacement is
      a recognised contributing factor in dislocation and early wear. During non
      navigated surgery, insertion of the acetabular component has traditionally been
      performed at an angle of 45 degrees relative to the sagittal plane as judged by
      the surgeon's eye, the operative inclination. Typically, the method used to
      assess inclination is the measurement made on the postoperative anteroposterior
      radiograph, the radiological inclination. The aim of this study was to measure
      the intra-operative angle of inclination of the acetabular component on 60
      consecutive patients in the lateral decubitus position when using a posterior
      approach during total hip replacement. This was achieved by taking intra
      operative photographs of the acetabular inserter, representing the acetabular
      axis, and a horizontal reference. The results were compared with the post
      operative radiological inclination. The mean post-operative radiological
      inclination was 13 degrees greater than the photographed operative inclination,
      which was unexpectedly high. It appears that in the lateral decubitus position
      with a posterior approach, the uppermost hemipelvis adducts, thus reducing the
      apparent operative inclination. Surgeons using the posterior approach in lateral
      decubitus need to aim for a lower operative inclination than when operating with
      the patient supine in order to achieve an acceptable radiological inclination.

PMID- 20798437
TI  - Grafting with hydroxyapatite granules for defects of acetabular bone at revision
      total hip replacement: a minimum ten-year follow-up.
AB  - The long-term results of grafting with hydroxyapatite granules for acetabular
      deficiency in revision total hip replacement are not well known. We have
      evaluated the results of revision using a modular cup with hydroxyapatite
      grafting for Paprosky type 2 and 3 acetabular defects at a minimum of ten years'
      follow-up. We retrospectively reviewed 49 acetabular revisions at a mean of 135
      months (120 to 178). There was one type 2B, ten 2C, 28 3A and ten 3B hips. With
      loosening as the endpoint, the survival rate was 74.2% (95% confidence interval
      58.3 to 90.1). Radiologically, four of the type 3A hips (14%) and six of the type
      3B hips (60%) showed aseptic loosening with collapse of the hydroxyapatite layer,
      whereas no loosening occurred in type 2 hips. There was consolidation of the
      hydroxyapatite layer in 33 hips (66%). Loosening was detected in nine of 29 hips
      (31%) without cement and in one of 20 hips (5%) with cement (p = 0.03, Fisher's
      exact probability test). The linear wear and annual wear rate did not correlate
      with loosening. These results suggest that the long-term results of
      hydroxyapatite grafting with cement for type 2 and 3A hips are encouraging.

PMID- 20798438
TI  - Outcomes of revision total hip replacement for infection after grading according
      to a standard protocol.
AB  - Periprosthetic infection following total hip replacement can be a catastrophic
      complication for the patient. The treatments available include single-stage
      exchange, and two-stage exchange. We present a series of 50 consecutive patients
      with a diagnosis of infected total hip replacement who were assessed according to
      a standardised protocol. Of these, 11 underwent single-stage revision
      arthroplasty with no recurrence of infection at a mean of 6.8 years follow-up
      (5.5 to 8.8). The remaining 39 underwent two-stage revision, with two recurrences
      of infection successfully treated by a second two-stage procedure. At five years,
      significant differences were found in the mean Harris Hip Scores (single-stage
      87.8; two-stage 75.5; p = 0.0003) and in a visual analogue score for satisfaction
      (8.6; 6.9; p = 0.001) between the single- and two-stage groups. Single-stage
      exchange is successful in eradicating periprosthetic infection and results in
      excellent functional and satisfaction scores. Identification of patients suitable
      for the single-stage procedure allows individualisation of care and provides as
      many as possible with the correct strategy in successfully tackling their
      periprosthetic infection.

PMID- 20798439
TI  - Five-year survival of nonagenerian patients undergoing total hip replacement in
      the United Kingdom.
AB  - Between January 2000 and December 2007, 31 patients 90 years of age or older
      underwent total hip replacement at our hospital. Their data were collected
      prospectively. The rate of major medical complications was 9%. The surgical re
      operation rate was 3%. The requirement for blood transfusion was 71% which was
      much higher than for younger patients. The 30-day, one-year and current mortality
      figures were 6.4% (2 of 31), 9.6% (3 of 31) and 55% (17 of 31), respectively,
      with a mean follow-up for the 14 surviving patients of six years. Cox's
      regression analysis revealed no significant independent predictors of mortality.
      Only 52% of patients returned immediately to their normal abode, with 45%
      requiring a prolonged period of rehabilitation. This is the first series to
      assess survival five years after total hip replacement for patients in their 90th
      year and beyond. Hip replacement in the extreme elderly should not be discounted
      on the grounds of age alone, although the complication rate exceeds that for
      younger patients. It can be anticipated that almost half of the patients will
      survive five years after surgery.

PMID- 20798440
TI  - Mid-term results of a custom-made short proximal loading femoral component.
AB  - Bone preservation and physiological distribution of forces on the proximal femur
      are key elements in introducing a successful uncemented total hip replacement. In
      order to achieve this, in the mid 1990s, we developed an ultra short proximal
      loading custom-made component with a lateral flare, a high femoral neck osteotomy
      and without a diaphyseal stem. We report the outcome of 129 custom-made
      hydroxyapatite-coated uncemented short femoral components inserted into 109
      patients between June 1995 and May 2004. The mean age of the patients was 51
      years (21 to 71) and the mean follow-up was eight years (4.9 to 14.1). Bone
      behaviour around the implant was studied on the post-operative radiographs. The
      mean Harris hip score improved from 44 (8 to 66) pre-operatively to 95 (76 to
      100) at final follow-up. The Western Ontario MacMaster University Osteoarthritis
      index was 93 of 100 at final review. None of the patients reported thigh pain. A
      total of five hips were revised, three for polyethylene liner exchange and two
      for complete revision of the acetabular component. No femoral components were
      revised. The radiological changes in the proximal femur were generally good, as
      evidenced by spot welds both on the medial and lateral aspects of the femur. No
      component migrated. The presence of a lateral flare and use of a high osteotomy
      of the femoral neck provided good clinical and radiological results. The absence
      of a diaphyseal portion of the stem did not impair stability.

PMID- 20798441
TI  - Internal rotational error of the tibial component is a major cause of pain after
      total knee replacement.
AB  - This study used CT analysis to determine the rotational alignment of 39 painful
      and 26 painless fixed-bearing total knee replacements (TKRs) from a cohort of 740
      NexGen Legacy posterior-stabilised and cruciate-retaining prostheses implanted
      between May 1996 and August 2003. The mean rotation of the tibial component was
      4.3 degrees of internal rotation (25.4 degrees internal to 13.9 degrees external
      rotation) in the painful group and 2.2 degrees of external rotation (8.5 degrees
      internal to 18.2 degrees external rotation) in the painfree group (p = 0.024). In
      the painful group 17 tibial components were internally rotated more than 9
      degrees compared with none in the painfree group (p < 0.001). Additionally, six
      femoral components in the painful group were internally rotated more than 6
      degrees compared with none in the painfree group (p = 0.017). External rotational
      errors were not found to be associated with pain. Overall, 22 (56.4%) of the
      painful TKRs had internal rotational errors involving the femoral, the tibial or
      both components. It is estimated that at least 4.6% of all our TKRs have been
      implanted with significant internal rotational errors.

PMID- 20798442
TI  - The complications of high tibial osteotomy: closing- versus opening-wedge
      methods.
AB  - We compared the incidence and severity of complications during and after closing-
      and opening-wedge high tibial osteotomy used for the treatment of varus arthritis
      of the knee, and identified the risk factors associated with the development of
      complications. In total, 104 patients underwent laterally based closing-wedge and
      90 medial opening-wedge high tibial osteotomy between January 1993 and December
      2006. The characteristics of each group were similar. All the patients were
      followed up for more than 12 months. We assessed the outcome using the Hospital
      for Special Surgery knee score, and recorded the complications. Age, gender,
      obesity (body mass index > 27.5 kg/m(2)), the type of osteotomy (closing versus
      opening) and the pre-operative mechanical axis were subjected to risk-factor
      analysis. The mean Hospital for Special Surgery score in the closing and opening
      groups improved from 73.4 (54 to 86) to 91.8 (81 to 100) and from 73.8 (56 to 88)
      to 93 (84 to 100), respectively. The incidence of complications overall and of
      major complications in both groups was not significantly different (p = 0.20
      overall complication, p = 0.29 major complication). Logistic regression analysis
      adjusting for obesity and the pre-operative mechanical axis showed that obesity
      remained a significant independent risk factor (odds ratio = 3.23) of a major
      complication after high tibial osteotomy. Our results suggest that the opening
      wedge high tibial osteotomy can be an alternative treatment option for young
      patients with medial compartment osteoarthritis and varus deformity.

PMID- 20798443
TI  - Predicting dissatisfaction following total knee replacement: a prospective study
      of 1217 patients.
AB  - Up to 20% of patients are not satisfied with the outcome following total knee
      replacement (TKR). This study investigated the pre- and post-operative predictors
      of dissatisfaction in a large cohort of patients undergoing TKR. We assessed 1217
      consecutive patients between 2006 and 2008 both before operation and six months
      after, using the Short-form (SF)-12 health questionnaire and the Oxford Knee
      Score. Detailed information concerning comorbidity was also gathered.
      Satisfaction was measured at one year when 18.6% (226 of 1217) of patients were
      unsure or dissatisfied with their replacement and 81.4% (911 of 1217) were
      satisfied or very satisfied. Multivariate regression analysis was performed to
      identify independent predictors of dissatisfaction. Significant (p < 0.001)
      predictors at one year included the pre-operative SF-12 mental component score,
      depression and pain in other joints, the six-month SF-12 score and poorer
      improvement in the pain element of the Oxford Knee Score. Patient expectations
      were highly correlated with satisfaction. Satisfaction following TKR is
      multifactorial. Managing the expectations and mental health of the patients may
      reduce dissatisfaction. However, the most significant predictor of
      dissatisfaction is a painful total knee replacement.

PMID- 20798444
TI  - Electrocautery of the patellar rim in primary total knee replacement: beneficial
      or unnecessary?
AB  - The management of the patella during total knee replacement is controversial. In
      some studies the absence of patellar resurfacing results in residual anterior
      knee pain in over 10% of patients. One form of treatment which may be used in an
      endeavour to reduce this is circumferential patellar rim electrocautery. This is
      believed to partially denervate the patella. However, there is no evidence of the
      efficacy of this procedure, nor do we know if it results in harm. A retrospective
      comparative cohort study was performed of 192 patients who had undergone a
      primary total knee replacement with the porous coated Low Contact Stress rotating
      platform prosthesis without patellar resurfacing between 2003 and 2007. In 98
      patients circumferential electrocautery of the patellar rim was performed and in
      94 patients it was not. The two groups were matched for gender and age. The
      general Oxford Knee Score and the more specific patellar score for anterior knee
      pain were used to assess patient outcomes a minimum of two years post
      operatively. No statistically significant differences were noted between the
      groups for either scoring system (p = 0.41 and p = 0.87, respectively).
      Electrocautery of the patella rim did not improve the outcome scores after
      primary total knee replacement in our patients.

PMID- 20798445
TI  - Extensor hallucis longus transfer as an alternative to split transfer of the
      tibialis anterior tendon to correct equinovarus foot in hemiplegic patients
      without overactivity of tibialis anterior.
AB  - This study assessed if transfer of the extensor hallucis longus is a valid
      alternative treatment to split transfer of the tibialis anterior tendon in adult
      hemiplegic patients without overactivity of the tibialis anterior. One group of
      15 patients had overactivity of tibialis anterior in the swing phase, and
      underwent the split transfer. A further group of 14 patients had no overactivity
      of tibialis anterior, and underwent transfer of extensor hallucis longus. All
      patients had lengthening of the tendo Achillis and tenotomies of the toe flexors.
      All were evaluated clinically and by three-dimensional gait analysis pre- and at
      one year after surgery. At this time both groups showed significant reduction of
      disability in walking. Gait speed, stride length and paretic propulsion had
      improved significantly in both groups. Dorsiflexion in the swing phase, the step
      length of the healthy limb and the step width improved in both groups, but only
      reached statistical significance in the patients with transfer of the extensor
      hallucis longus. There were no differences between the groups at one year after
      operation. When combined with lengthening of the tendo Achillis, transfer of the
      extensor hallucis longus can be a valid alternative to split transfer of the
      tibialis anterior tendon to correct equinovarus foot deformity in patients
      without overactivity of tibialis anterior.

PMID- 20798446
TI  - The effectiveness of interventions in the management of patients with primary
      frozen shoulder.
AB  - There are many types of treatment used to manage the frozen shoulder, but there
      is no consensus on how best to manage patients with this painful and debilitating
      condition. We conducted a review of the evidence of the effectiveness of
      interventions used to manage primary frozen shoulder using the Cochrane Database
      of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the
      Physiotherapy Evidence Database, MEDLINE and EMBASE without language or date
      restrictions up to April 2009. Two authors independently applied selection
      criteria and assessed the quality of systematic reviews using the Assessment of
      Multiple Systematic Reviews (AMSTAR) tool. Data were synthesised narratively,
      with emphasis placed on assessing the quality of evidence. In total, 758 titles
      and abstracts were identified and screened, which resulted in the inclusion of 11
      systematic reviews. Although these met most of the AMSTAR quality criteria, there
      was insufficient evidence to draw firm conclusions about the effectiveness of
      treatments commonly used to manage a frozen shoulder. This was mostly due to poor
      methodological quality and small sample size in primary studies included in the
      reviews. We found no reviews evaluating surgical interventions. More rigorous
      randomised trials are needed to evaluate the treatments used for frozen shoulder.

PMID- 20798447
TI  - Revision interposition arthroplasty of the elbow.
AB  - Between 1996 and 2008, nine patients with severe post-traumatic arthritis
      underwent revision of a failed interposition arthroplasty of the elbow with a
      further interposition procedure using an allograft of tendo Achillis at a mean of
      5.6 years (0.7 to 13.1) after the initial procedure. There were eight men and one
      woman with a mean age of 47 years (36 to 56). The mean follow-up was 4.7 years (2
      to 8). The mean Mayo Elbow Performance score improved from 49 (15 to 65) pre
      operatively to 73 (55 to 95) (p = 0.04). The mean Disability of the Arm, Shoulder
      and Hand score was 26 (7 to 42). One patient was unavailable for clinical follow
      up and one underwent total elbow replacement three months post-operatively. Of
      the remaining patients, one had an excellent, two had good, three fair and one a
      poor result. Subjectively, five of the nine patients were satisfied. Four
      continued manual labour. Revision interposition arthroplasty is an option for
      young, active patients with severe post-traumatic arthritis who require both
      mobility and durability of the elbow.

PMID- 20798448
TI  - Operative treatment of Linburg-Comstock syndrome.
AB  - Linburg-Comstock syndrome is characterised by an anomalous tendon slip from the
      flexor pollicis longus to the flexor digitorum profundus, usually of the index
      finger. An incidence as high as 60% to 70% has been reported. Post-traumatic
      inflammation of inter-tendinous connections between the flexor pollicis longus
      and flexor digitorum profundus, usually of the index finger, may cause
      unexplained chronic pain in the distal forearm. A total of 11 patients (eight
      females, three males), mean age 29.1 years (14 to 47) with a clinical diagnosis
      of Linburg-Comstock syndrome underwent surgical release of the inter-tendinous
      connection. The mean follow-up was for 27 months (2 to 48). Ten patients reported
      excellent relief of pain in the forearm, with independent flexion of flexor
      pollicis longus and flexor digitorum profundus to the index finger. Surgical
      release was an effective treatment for the Linburg-Comstock syndrome in this
      series.

PMID- 20798449
TI  - A prospective comparative study of kyphoplasty using the Jack vertebral dilator
      and balloon kyphoplasty for the treatment of osteoporotic vertebral compression
      fractures.
AB  - This study prospectively compared the efficacy of kyphoplasty using a Jack
      vertebral dilator and balloon kyphoplasty to treat osteoporotic compression
      fractures between T10 and L5. Between 2004 and 2009, two groups of 55 patients
      each underwent vertebral dilator kyphoplasty and balloon kyphoplasty,
      respectively. Pain, function, the Cobb angle, and the anterior and middle height
      of the vertebral body were assessed before and after operation. Leakage of bone
      cement was recorded. The post-operative change in the Cobb angle was
      significantly greater in the dilator kyphoplasty group than in the balloon
      kyphoplasty group (-9.51 degrees (sd 2.56) vs -7.78 degrees (sd 1.19), p <
      0.001)). Leakage of cement was less in the dilator kyphoplasty group. No other
      significant differences were found in the two groups after operation, and both
      procedures gave equally satisfactory results in terms of all other variables
      assessed. No serious complications occurred in either group. These findings
      suggest that vertebral dilator kyphoplasty can facilitate better correction of
      kyphotic deformity and may ultimately be a safer procedure in reducing leakage of
      bone cement.

PMID- 20798450
TI  - Septic arthritis or transient synovitis of the hip in children: the value of
      clinical prediction algorithms.
AB  - The crucial differentiation between septic arthritis and transient synovitis of
      the hip in children can be difficult. In 1999, Kocher et al introduced four
      clinical predictors which were highly predictive (99.6%) of septic arthritis.
      These included fever (temperature > or = 38.5 degrees C), inability to bear
      weight, white blood-cell count > 12.0 x 10(9) cells/L and ESR > or = 40 mm/hr;
      CRP > or = 20 mg/L was later added as a fifth predictor. We retrospectively
      evaluated these predictors to differentiate septic arthritis from transient
      synovitis of the hip in children over a four-year period in a primary referral
      general hospital. When all five were positive, the predicted probability of
      septic arthritis in this study was only 59.9%, with fever being the best
      predictor. When applied to low-prevalence diseases, even highly specific tests
      yield a high number of false positives and the predictive value is thereby
      diminished. Clinical predictors should be applied with caution when assessing a
      child with an irritable hip, and a high index of suspicion, and close observation
      of patients at risk should be maintained.

PMID- 20798451
TI  - How will surgical site infection be measured to ensure "high quality care for
      all"?
AB  - As of April 2010 all NHS institutions in the United Kingdom are required to
      publish data on surgical site infection, but the method for collecting this has
      not been decided. We examined 7448 trauma and orthopaedic surgical wounds made in
      patients staying for at least two nights between 2000 and 2008 at our institution
      and calculated the rate of surgical site infection using three definitions: the
      US Centers for Disease Control, the United Kingdom Nosocomial Infection National
      Surveillance Scheme and the ASEPSIS system. On the same series of wounds, the
      infection rate with outpatient follow-up according to Centre for Disease Control
      was 15.45%, according to the UK Nosocomial infection surveillance was 11.32%, and
      according to ASEPSIS was 8.79%. These figures highlight the necessity for all
      institutions to use the same method for diagnosing surgical site infection. If
      different methods are used, direct comparisons will be invalid and published
      rates of infection will be misleading.

PMID- 20798452
TI  - Congenital absence of the posterior arch of the atlas associated with a fracture
      of the anterior arch.
AB  - Structural defects of the posterior arch of the atlas are rare, and range from
      clefts of variable location and size to more extensive defects such as complete
      agenesis. These abnormalities are usually incidental radiological findings. We
      present a case of a fracture of the anterior arch of the atlas associated with a
      congenital abnormality of the posterior arch.

PMID- 20798453
TI  - Customised femoral stems in osteopetrosis and the development of a guiding system
      for the preparation of an intramedullary cavity: a report of two cases.
AB  - Traditional techniques for the insertion of femoral stems in arthroplasty of the
      hip in osteopetrosis carry a considerable risk of penetration of the femoral
      cortex and intra-operative fractures, due to obliteration of the intramedullary
      cavity and greatly increased stiffness and brittleness of the bone. In order to
      reduce the risk of such complications we manufactured a customised stem and a
      computer-based guiding device for the preparation of a cavity within the proximal
      femur. This system was used successfully in three hips in two patients. We
      describe the system and the operative technique.

PMID- 20798454
TI  - Delamination of a highly cross-linked polyethylene liner associated with titanium
      deposits on the cobalt-chromium modular femoral head following dislocation.
AB  - Retrieval studies of total hip replacements with highly cross-linked ultra-high
      molecular-weight polyethylene liners have shown much less surface damage than
      with conventional ultra-high-molecular-weight polyethylene liners. A recent
      revision hip replacement for recurrent dislocation undertaken after only five
      months revealed a highly cross-linked polyethylene liner with a large area of
      visible delamination. In order to determine the cause of this unusual surface
      damage, we analysed the bearing surfaces of the cobalt-chromium femoral head and
      the acetabular liner with scanning electron microscopy, energy dispersive x-ray
      spectroscopy and optical profilometry. We concluded that the cobalt-chromium
      modular femoral head had scraped against the titanium acetabular shell during the
      course of the dislocations and had not only roughened the surface of the femoral
      head but also transferred deposits of titanium onto it. The largest deposits were
      1.6 microm to 4.3 microm proud of the surrounding surface and could lead to
      increased stresses in the acetabular liner and therefore cause accelerated wear
      and damage. This case illustrates that dislocations can leave titanium deposits
      on cobalt-chromium femoral heads and that highly cross-linked ultra-high
      molecular-weight polyethylene remains susceptible to surface damage.

PMID- 20798455
TI  - Shenton's line.
AB  - This paper considers the history of Shenton's line.

PMID- 20798456
TI  - Anatomy of piriformis, obturator internus and obturator externus: implications
      for the posterior surgical approach to the hip.
AB  - We dissected 20 cadaver hips in order to investigate the anatomy and excursion of
      the trochanteric muscles in relation to the posterior approach for total hip
      replacement. String models of each muscle were created and their excursion
      measured while the femur was moved between its anatomical position and the
      dislocated position. The position of the hip was determined by computer
      navigation. In contrast to previous studies which showed a separate insertion of
      piriformis and obturator internus, our findings indicated that piriformis
      inserted onto the superior and anterior margins of the greater trochanter through
      a conjoint tendon with obturator internus, and had connections to gluteus medius
      posteriorly. Division of these connections allowed lateral mobilisation of
      gluteus medius with minimal retraction. Analysis of the excursion of these
      muscles revealed that positioning the thigh for preparation of the femur through
      this approach elongated piriformis to a maximum of 182%, obturator internus to
      185% and obturator externus to 220% of their resting lengths, which are above the
      thresholds for rupture of these muscles. Our findings suggested that gluteus
      medius may be protected from overstretching by release of its connection with the
      conjoint tendon. In addition, failure to detach piriformis or the obturators
      during a posterior approach for total hip replacement could potentially produce
      damage to these muscles because of over-stretching, obturator externus being the
      most vulnerable.

PMID- 20798457
TI  - Elastographic contrast generation in optical coherence tomography from a
      localized shear stress.
AB  - A technique for generating contrast in two-dimensional shear strain elastograms
      from a localized stress is presented. The technique involves generating a non
      uniform, localized stress via a magnetically actuated implant. Its effectiveness
      is demonstrated using finite-element simulations and a phantom study provides
      experimental verification of this. The method is applied to a superficial
      cancerous lesion model represented as a stiff inclusion in normal tissue. The
      lesion was best distinguished from its surroundings using total shear strain
      elastograms, rather than individual strain components. In experimental phantom
      studies, the lesion was imaged using optical coherence tomography (OCT) and could
      still be distinguished in elastograms when not readily identifiable in standard
      OCT images.

PMID- 20798458
TI  - Interior point algorithms: guaranteed optimality for fluence map optimization in
      IMRT.
AB  - One of the most widely studied problems of the intensity-modulated radiation
      therapy (IMRT) treatment planning problem is the fluence map optimization (FMO)
      problem, the problem of determining the amount of radiation intensity, or
      fluence, of each beamlet in each beam. For a given set of beams, the fluences of
      the beamlets can drastically affect the quality of the treatment plan, and thus
      it is critical to obtain good fluence maps for radiation delivery. Although
      several approaches have been shown to yield good solutions to the FMO problem,
      these solutions are not guaranteed to be optimal. This shortcoming can be
      attributed to either optimization model complexity or properties of the
      algorithms used to solve the optimization model. We present a convex FMO
      formulation and an interior point algorithm that yields an optimal treatment plan
      in seconds, making it a viable option for clinical applications.

PMID- 20798459
TI  - The effect of volume-of-interest misregistration on quantitative planar activity
      and dose estimation.
AB  - In targeted radionuclide therapy (TRT), dose estimation is essential for
      treatment planning and tumor dose response studies. Dose estimates are typically
      based on a time series of whole-body conjugate view planar or SPECT scans of the
      patient acquired after administration of a planning dose. Quantifying the
      activity in the organs from these studies is an essential part of dose
      estimation. The quantitative planar (QPlanar) processing method involves accurate
      compensation for image degrading factors and correction for organ and background
      overlap via the combination of computational models of the image formation
      process and 3D volumes of interest defining the organs to be quantified. When the
      organ VOIs are accurately defined, the method intrinsically compensates for
      attenuation, scatter and partial volume effects, as well as overlap with other
      organs and the background. However, alignment between the 3D organ volume of
      interest (VOIs) used in QPlanar processing and the true organ projections in the
      planar images is required. The aim of this research was to study the effects of
      VOI misregistration on the accuracy and precision of organ activity estimates
      obtained using the QPlanar method. In this work, we modeled the degree of
      residual misregistration that would be expected after an automated registration
      procedure by randomly misaligning 3D SPECT/CT images, from which the VOI
      information was derived, and planar images. Mutual information-based image
      registration was used to align the realistic simulated 3D SPECT images with the
      2D planar images. The residual image misregistration was used to simulate
      realistic levels of misregistration and allow investigation of the effects of
      misregistration on the accuracy and precision of the QPlanar method. We observed
      that accurate registration is especially important for small organs or ones with
      low activity concentrations compared to neighboring organs. In addition, residual
      misregistration gave rise to a loss of precision in the activity estimates that
      was on the order of the loss of precision due to Poisson noise in the projection
      data. These results serve as a lower bound on the effects of misregistration on
      the accuracy and precision of QPlanar activity estimate and demonstrate that
      misregistration errors must be taken into account when assessing the overall
      precision of organ dose estimates.

PMID- 20798460
TI  - The radiation dose from a proposed measurement of arsenic and selenium in human
      skin.
AB  - Dose measurements following 10 min irradiations with a portable x-ray
      fluorescence spectrometer composed of a miniature x-ray tube and a silicon PiN
      diode detector were performed using thermoluminescent dosimeters consisting of
      LiF:Mg,Ti chips of 3 mm diameter and 0.4 mm thickness. The table-top setup of the
      spectrometer was used for all measurements. The setup included a stainless steel
      lid which served as a radiation shield. Two rectangular polyethylene skin/soft
      tissue phantoms with two cylindrical plaster of Paris bone phantoms were used to
      study the effect of x-ray beam attenuation and backscatter on the measured dose.
      Eight different irradiation experiments were performed. The average dose rate
      values measured with TLD chips within a 1 x 1 cm(2) area were between 4.8 and
      12.8 mGy min(-1). The equivalent dose for a 1 x 1 cm(2) skin area was estimated
      to be 13.2 mSv. The maximum measured dose rate values with a single TLD chip were
      between 7.5 and 25.1 mGy min(-1). The effective dose corresponding to a proposed
      arsenic/selenium skin measurement was estimated to be 0.13 microSv for a 2 min
      irradiation.

PMID- 20798461
TI  - Direct manipulation of intracellular stress fibres using a hook-shaped AFM probe.
AB  - Atomic force microscopy (AFM) is a highly successful technique for imaging
      nanometre-sized samples and measuring pico- to nano-newton forces acting between
      atoms and molecules. When it comes to the manipulation of larger samples with
      forces of tens and hundreds of nano-newtons, however, the present chemistry-based
      modification protocols for functionalizing AFM cantilevers to achieve the
      formation of covalent/non-covalent linkages between the AFM probe and the sample
      surface do not produce strong enough bonds. For the purpose of measuring the
      fracture strength and other mechanical properties of stress fibres (SFs) in
      living as well as semi-intact fibroblast cells, we fabricated an AFM probe with a
      hooking function by focused ion beam technology and used the AFM probe hook to
      capture, pull and eventually sever a chosen SF labelled with green or red
      fluorescent protein.

PMID- 20798462
TI  - Nanocap arrays of granular CoCrPt:SiO2 films on silica particles: tailoring of
      the magnetic properties by Co+ irradiation.
AB  - An approach for tailoring the magnetic properties by ion irradiation of granular
      perpendicular CoCrPt:SiO(2) films grown on silica particles with sizes down to 10
      nm was investigated. The as-prepared samples reveal an intriguing scaling
      dependence of the coercive field and remnant magnetization: both parameters are
      found to decrease with decreasing particle size. However, Co(+) irradiation at a
      low fluence of 0.5 x 10(14) cm(-2) already results in an opposite scaling
      behavior. It is assumed that this modification is due to the enhancement of the
      intergranular magnetic exchange coupling of the granular CoCrPt:SiO(2) film
      initiated by Co(+) irradiation resulting in a modified reversal behavior. Further
      increase of the irradiation fluence beyond 1.6 x 10(14) ions cm(-2) leads to a
      degradation of the magnetic layer properties, lowering the remnant magnetization
      and the coercive field in the easy-axis direction. Moreover, the local magnetic
      properties of the samples were analyzed by magnetic force microscopy revealing
      magnetic multi-domain cap structures.

PMID- 20798463
TI  - Carbon nanotubes decorated with gold, platinum and rhodium clusters by injection
      of colloidal solutions into the post-discharge of an RF atmospheric plasma.
AB  - In this paper, we present a new, simple, robust and efficient technique to
      decorate multi-wall carbon nanotubes (MWCNT) with metal nanoparticles. As case
      studies, Au, Pt and Rh nanoparticles are grafted onto MWCNTs by spraying a
      colloidal solution into the post-discharge of an atmospheric argon or
      argon/oxygen RF plasma. The method that we introduce here is different from those
      usually described in the literature, since the treatment is operated at
      atmospheric pressure, allowing the realization in only one step of the surface
      activation and the deposition processes. We demonstrate experimentally that the
      addition of oxygen gas in the plasma increases significantly the amount of
      grafted metal nanoparticles. Moreover, TEM pictures clearly show that the grafted
      nanoparticles are well controlled in size.

PMID- 20798464
TI  - Highly efficient siRNA delivery system into human and murine cells using single
      wall carbon nanotubes.
AB  - Development of RNA interference (RNAi) technology utilizing short interfering RNA
      sequences (siRNA) has focused on creating methods for delivering siRNAs to cells
      and for enhancing siRNA stability in vitro and in vivo. Here, we describe a novel
      approach for siRNA cellular delivery using siRNA coiling into carboxyl
      functionalized single-wall carbon nanotubes (SWCNTs). The CNT-siRNA delivery
      system successfully demonstrates nonspecific toxicity and transfection efficiency
      greater than 95%. This approach offers the potential for siRNA delivery into
      different types of cells, including hard-to-transfect cells, such as neuronal
      cells and cardiomyocytes. We also tested the CNT-siRNA system in a non-metastatic
      human hepatocellular carcinoma cell line (SKHep1). In all types of cells used in
      this work the CNT-siRNA delivery system showed high efficiency and apparent no
      side effects for various in vitro applications.

PMID- 20798465
TI  - Enhanced visible photoluminescence from ultrathin ZnO films grown on Si-nanowires
      by atomic layer deposition.
AB  - Bright room temperature visible emission is obtained in heterostructures
      consisting of approximately 3.5 nm thick ZnO ultrathin films grown on Si
      nanowires produced by means of self-masking dry etching in hydrogen-containing
      plasma. The ZnO films were deposited on Si-nanowires by using atomic layer
      deposition (ALD) under an ambient temperature of 25 degrees C. The orders of
      magnitude enhancement in the intensity of the room temperature photoluminescence
      peaked around 560 nm in the present ZnO/Si-nanowire heterostructures is
      presumably due to the high aspect (surface/volume) ratio inherent to the Si
      nanowires, which has, in turn, allowed considerably more ZnO material to be grown
      on the template and led to markedly more efficient visible emission. Moreover,
      the ordered nanowire structure also features an extremely low reflectance
      (approximately 0.15%) at 325 nm, which may further enhance the efficiency of
      emission by effectively trapping the excitation light.

PMID- 20798466
TI  - Ionic liquid templated porous nano-TiO2 particles for the selective isolation of
      cytochrome c.
AB  - Porous nano-titanium dioxide (TiO(2)) particles with anatase framework were
      prepared by using an effective template of hydrophobic ionic liquid, i.e., N, N
      bis [2-methylbutyl] imidazolium hexafluorophosphate ([PPim][PF(6)]). The nano
      TiO(2) particles were characterized with TEM and BET, resulting in the
      distribution of the pore diameters centering at 7.3 nm and 26.2 nm, attributed to
      the template effect of the ionic liquid and the aggregation of the TiO(2)
      particles, respectively. A much improved surface area of 68.31 m(2) g(-1) and a
      pore volume of 0.2814 cm(3) g(-1) were obtained with respect to 15.16 m(2) g(-1)
      and 0.0402 cm(3) g(-1) achieved by the non-templated nano-TiO(2) counterpart. The
      porous nano-TiO(2) particles were used as adsorbent for selective adsorption and
      isolation of cytochrome c (cyt-c) at certain conditions. An adsorption efficiency
      of 87% was achieved for 150 microg ml(-1) cyt-c in 1.0 ml of sample solution at
      pH 9.0 by using 2.0 mg of the nano-TiO(2) particles, in comparison to 30%
      obtained by the non-templated nano-TiO(2). In addition, an adsorption capacity of
      112.6 microg mg(-1) was derived for the porous nano-TiO(2) with respect to 25.1
      microg mg(-1) for the normal ones. The absorbed cyt-c could be readily recovered
      by stripping with a 0.1 mol l(-1) Na(3)PO(4) solution, giving rise to a recovery
      of ca. 90%. The porous nano-TiO(2) particles have been used for the isolation of
      cyt-c from human whole blood, achieving satisfactory results by assay with SDS
      PAGE.

PMID- 20798467
TI  - Gold-free growth of GaAs nanowires on silicon: arrays and polytypism.
AB  - We report growth by molecular beam epitaxy and structural characterization of
      gallium-nucleated GaAs nanowires on silicon. The influences of growth temperature
      and V/III ratio are investigated and compared in the case of oxide-covered and
      oxide-free substrates. We demonstrate a precise positioning process for Ga
      nucleated GaAs nanowires using a hole array in a dielectric layer thermally grown
      on silicon. Crystal quality is analyzed by high resolution transmission electron
      microscopy. Crystal structure evolves from pure zinc blende to pure wurtzite
      along a single nanowire, with a transition region.

PMID- 20798468
TI  - DC modeling and the source of flicker noise in passivated carbon nanotube
      transistors.
AB  - DC and intrinsic low-frequency noise properties of p-channel depletion-mode
      carbon nanotube field effect transistors (CNT-FETs) are investigated. To
      characterize the intrinsic noise properties, a thin atomic layer deposited (ALD)
      HfO(2) gate dielectric is used as a passivation layer to isolate CNT-FETs from
      environmental factors. The ALD HfO(2) gate dielectric in these high-performance
      top-gated devices is instrumental in attaining hysteresis-free current-voltage
      characteristics and minimizes low-frequency noise. Under small drain-source
      voltage, the carriers in the CNT channel are modulated by the gate electrode and
      the intrinsic 1/f noise is found to be correlated with charge trapping/detrapping
      from the oxide substrate as expected. When thermionic emission is the dominant
      carrier transport mechanism in CNT-FETs under large drain-source voltages, the
      excess 1/f noise is attributed to the noise stemming from metal-CNT Schottky
      barrier contacts as revealed by the measurements.

PMID- 20798469
TI  - A six degree of freedom nanomanipulator design based on carbon nanotube bundles.
AB  - Scanning probe imaging and manipulation of matter is of crucial importance for
      nanoscale science and technology. However, its resolution and ability to
      manipulate matter at the atomic scale is limited by rather poor control over the
      fine structure of the probe. In the present paper, a strategy is proposed to
      construct a molecular nanomanipulator from ultrathin single-walled carbon
      nanotubes. Covalent modification of a nanotube cap at predetermined atomic sites
      makes the nanotube act as a support for a functional 'tooltip' molecule. Then, a
      small bundle of nanotubes (three or four) with aligned ends can act as an
      extremely high aspect ratio parallel nanomanipulator for a suspended molecule,
      where protraction or retraction of individual nanotubes results in controlled
      tilting of the tooltip in two dimensions. Together with the usual scanning probe
      microscopy three degrees of freedom and augmented with rotation of the system as
      a whole, the design offers six degrees of freedom for imaging and manipulation of
      matter with the precision and freedom so much needed for advanced nanotechnology.
      A similar design might be possible to implement with other high aspect ratio
      nanostructures, such as oxide nanowires.

PMID- 20798470
TI  - ZnS:Cu,Co water-soluble afterglow nanoparticles: synthesis, luminescence and
      potential applications.
AB  - Cu(2+) and Co(2+) co-doped zinc sulfide water-soluble nanoparticles (ZnS:Cu,Co)
      were prepared and their afterglow luminescence was observed and reported for the
      first time. The nanoparticles have a cubic zinc blende structure with average
      sizes of about 4 nm as determined by high-resolution transmission electron
      microscopy (HRTEM) and x-ray diffraction (XRD). In the photoluminescence, two
      emission peaks are observed at 470 and 510 nm. However, in the afterglow, only
      one peak is observed at around 525 nm. The blue emission at 470 nm is from
      surface states and the green emission at 525 nm is from Cu(2+). This means that
      Cu(2+) is responsible for the afterglow from the nanoparticles, while the co
      doping of Co(2+) is critical for the afterglow because no afterglow could be seen
      without co-doping with Co(2+). The successful observation of the afterglow from
      water-soluble nanoparticles may open up new applications of afterglow phosphors
      in biological imaging, detection and treatment.

PMID- 20798471
TI  - Retention of tritium in reference persons: a metabolic model. Derivation of
      parameters and application of the model to the general public and to workers.
AB  - Tritium ((3)H) is a radioactive isotope of hydrogen that is ubiquitous in
      environmental and biological systems. Following debate on the human health risk
      from exposure to tritium, there have been claims that the current biokinetic
      model recommended by the International Commission on Radiological Protection
      (ICRP) may underestimate tritium doses. A new generic model for tritium in
      mammals, based on energy metabolism and body composition, together with all its
      input data, has been described in a recent paper and successfully tested for farm
      and laboratory mammals. That model considers only dietary intake of tritium and
      was extended to humans. This paper presents the latest development of the human
      model with explicit consideration of brain energy metabolism. Model testing with
      human experimental data on organically bound tritium (OBT) in urine after
      tritiated water (HTO) or OBT intakes is presented. Predicted absorbed doses show
      a moderate increase for OBT intakes compared with doses recommended by the ICRP.
      Infants have higher tritium retention-a factor of 2 longer than the ICRP
      estimate. The highest tritium concentration is in adipose tissue, which has a
      very low radiobiological sensitivity. The ranges of uncertainty in retention and
      doses are investigated. The advantage of the new model is its ability to be
      applied to the interpretation of bioassay data.

PMID- 20798472
TI  - Estimation of seasonal correction factors through Fourier decomposition analysis-
      a new model for indoor radon levels in Irish homes.
AB  - Radon concentrations in homes have been shown to vary considerably with season.
      It is important to account for this by applying a correction factor to any home
      radon measurement of less than one year. To date, Irish radon measurement
      services have used correction factors based on data derived for the UK in the
      1980s. In the absence of similar data for Ireland at the time, these were
      considered suitable for use due to the similarities between the climates, house
      types and lifestyles in the two countries. In order to better estimate the long
      term radon concentration, measurements from 5640 Irish homes were used to derive
      a set of correction factors specifically for Ireland. These were generated by
      means of Fourier decomposition analysis and the new correction factors compared,
      using 95% confidence intervals, to those derived for the UK using the same
      analysis and to those currently in use for Ireland. In both cases, a significant
      difference was found between 10 of the 12 monthly seasonal correction factors.
      This paper presents the methods used in detail and the results of the analysis.

PMID- 20798473
TI  - Mortality and cancer registration experience of the Sellafield workers known to
      have been involved in the 1957 Windscale accident: 50 year follow-up.
AB  - This paper studies the mortality and cancer morbidity of the 470 male workers
      involved in tackling the 1957 Sellafield Windscale fire or its subsequent clean
      up. Workers were followed up for 50 years to 2007, extending the follow-up of a
      previously published cohort study on the Windscale fire by 10 years. The size of
      the study population is small, but the cohort is of interest because of the
      involvement of the workers in the accident. Significant excesses of deaths from
      diseases of the circulatory system (standardised mortality ratio (SMR) = 120, 95%
      CI = 103-138; 194 deaths) driven by ischaemic heart disease (IHD) (SMR = 133, 95%
      CI = 112-157, 141 deaths) were found when compared with the population of England
      and Wales but not when compared with the population of Northwest England (SMR =
      105, 95% CI = 90-120 and SMR = 115, 95% CI = 97-136 respectively). When compared
      with those workers in post at the time of the fire but not directly involved in
      the fire the mortality rate from IHD among those involved in tackling the fire
      was raised but not statistically significantly (rate ratio (RR) = 1.11, 95% CI =
      0.92-1.33). A RR of 1.11 is consistent with an excess relative risk of 0.65 Sv(
      1) as reported in an earlier study of non-cancer mortality in the British Nuclear
      Fuels plc cohort of which these workers are a small but significant part. There
      was a statistically significant difference in lung cancer mortality (RR = 2.18,
      95% CI = 1.05-4.52) rates between workers who had received higher recorded
      external doses during the fire and those who had received lower external doses.
      Comparison of the mortality rates of workers directly involved in the accident
      with workers in post, but not so involved, showed no significant differences
      overall. On the basis of the use of a propensity score the average effect of
      involvement in the Windscale fire on all causes of death was - 2.13% (se = 3.64%,
      p = 0.56) though this difference is not statistically significant. The average
      effect of involvement in the Windscale fire was - 5.53% (se = 3.81, p = 0.15) for
      all cancers mortality and 6.60% (se = 4.03%, p = 0.10) for IHD mortality though
      neither figure was statistically significant. This analysis of the mortality and
      cancer morbidity experience of those Sellafield workers involved in the 1957
      Windscale fire does not reveal any measurable effect of the fire upon their
      health. Although this study has low statistical power for detecting small adverse
      effects, due to the relatively small number of workers, it does provide
      reassurance that no significant health effects are associated with the 1957
      Windscale fire even after 50 years of follow-up.

PMID- 20798474
TI  - Testicular cancer risk associated with occupational radiation exposure: a
      systematic literature review.
AB  - Testicular cancer is a rare disease, affecting mainly young men aged 15-49. There
      have been some recent reports that it might be associated with radiation
      exposure. We have systematically reviewed this topic. English-language articles
      published between 1990 and 2008 studying the relationship between occupational
      radiation exposure and testicular cancer were included. Risk of bias was assessed
      using a modified version of the EPHPP checklist. For ionising radiation we
      subdivided study populations into occupational groups. No pooled analysis was
      performed due to the heterogeneity of studies. Seven case-control and 30 cohort
      studies were included in the review. For radiation workers, one incidence study
      showed a significant increase and four showed no effect. Eight mortality studies
      did not indicate an effect while four showed a non-significant increase.
      Incidence among persons with military exposure was not increased in two studies
      and non-significantly increased in another two. Among aircrew studies, one showed
      no effect against five with slight increases. Medical exposure studies showed no
      increases. For EMF exposure, three studies showed no effect, two reported a
      significant and four a non-significant increase in incidence. Overall, there was
      very limited evidence for associations between occupational ionising radiation
      and testicular cancer, while there were some positive associations for EMF.
      Testicular cancer mortality is generally low and was not associated with
      radiation. New incidence studies are recommended to investigate the association
      between radiation exposure and testicular cancer where exposure is better
      specified and individually estimated.

PMID- 20798475
TI  - Serum FSH level below 10 mIU/mL at twelve years old is an index of spontaneous
      and cyclical menstruation in Turner syndrome.
AB  - The gonadal function of patients with Turner syndrome (TS) is variable.
      Individuals with mosaicism characterized by 45,X/46,XX or 45,X/47,XXX are more
      likely to experience spontaneous menarche compared with other karyotypes.
      Prepubertal gonadotropins of TS patients with spontaneous menarche are reportedly
      normal or significantly lower than those of patients with induced menarche. The
      present study investigated an index of spontaneous and cyclical menstruation at
      10-12 years old in TS. Subjects comprised 50 patients with TS, divided into three
      groups: Group A (n=7), with spontaneous menarche before 16 years old and regular
      menstruation for at least 1 year and 6 months; Group B (n=6), with irregular
      menstruation since menarche leading to secondary amenorrhea despite spontaneous
      menarche before 16 years old; and Group C (n=37), without spontaneous breast
      budding before 14 years old or without spontaneous menarche before 16 years old.
      Karyotype, LH and FSH concentrations at 10 and 12 years old were analyzed
      retrospectively. Spontaneous and cyclical menstruation was more frequently
      observed in TS with mosaicism characterized by 45,X/46,XX or 45,X/47,XXX than in
      TS with other karyotypes, as previously described. Spontaneous and cyclical
      menstruation in TS was observed when serum FSH level was <10 mIU/mL at 12 years
      old, suggesting this FSH level as an index of spontaneous and cyclical
      menstruation in TS.

PMID- 20798476
TI  - Associations of metabolic factors, especially serum retinol-binding protein 4
      (RBP4), with blood pressure in Japanese--the Tanno and Sobetsu study.
AB  - Excess secretion of various adipocyte-derived molecules has been linked with
      insulin resistance, obesity, diabetes, inflammation, atherosclerosis, and
      cardiovascular disease. Retinol-binding protein 4 (RBP4), one of the new
      adipocytokine, is recently reported to provide a link between insulin resistance
      and features of metabolic factors. Hypertension is one of the most influential
      risk factors among cardiovascular disease. We examined the relationship between
      systolic blood pressure (BP) levels and metabolic factors including homeostasis
      model assessment of insulin resistance (HOMA-R), high sensitivity c-reactive
      protein (hs-CRP), adiponectin, and RBP4. The subjects were 153 men aged 59 +/- 14
      years and 224 women aged 57 +/- 14 years who had undergone medical check-ups in
      rural communities in 2007. Systolic BP was positively correlated with HOMA-R, hs
      CRP and RBP4 but not with adiponectin in women. There was a positive significant
      relationship between serum RBP4 levels and blood pressure in women, but such a
      relationship was not found in men. Serum RBP4 levels were not correlated with
      HOMA-R in either men or women. Serum RBP4 levels negatively were correlated with
      estimated glomerular filtration rate (eGFR) in women but not in men. Multiple
      regression analysis revealed that serum RBP4 levels significantly were related to
      systolic BP independently of age, sex, body mass index (BMI), total cholesterol
      levels and eGFR. Our study showed that increased levels of RBP4 as well as HOMA-R
      and hs-CRP in women were significantly associated with increased levels of
      systolic BP.

PMID- 20798477
TI  - One-step multiplex reverse-transcriptase PCR for detecting pandemic (H1N1) 2009
      influenza virus.
AB  - Pandemic (H1N1) 2009 influenza has spread throughout the world since April 2009
      and has caused many human deaths since its first report in humans. Pandemic
      (H1N1) 2009 influenza virus was first identified in a Canadian pig herd in April
      2009 and has been reported in more than ten countries, including Korea. We
      developed a one-step multiplex reverse transcriptase polymerase chain reaction
      (RT-PCR) assay based on the matrix gene that discriminates pandemic (H1N1) 2009
      influenza virus from endemic swine influenza viruses. The sensitivity of this
      assay was 100 copies of in vitro-transcribed target RNA and 0.01 tissue culture
      infective dose (TCID(50)/ml) of virus and was as high as those of conventional
      influenza A virus common matrix reverse transcriptase PCR assays and real-time
      reverse transcriptase PCR assays (1 to 200 copies) developed for detecting
      pandemic (H1N1) 2009 influenza viruses from human and pig samples. This one-step
      multiplex RT-PCR assay would be a good tool in monitoring pandemic (H1N1) 2009
      influenza virus among pig herds on a regular basis.

PMID- 20798478
TI  - Comparison of multiple steroid concentrations in serum and dried blood spots
      throughout the day of patients with congenital adrenal hyperplasia.
AB  - BACKGROUND/AIM: periodic measurement of plasma concentrations of cortisol
      precursors on a clinic visit may be of limited value in patients with congenital
      adrenal hyperplasia because it does not reflect a patient's circadian patterns of
      adrenal steroid secretion. Steroid profiling in dried blood spots (DBS) may allow
      for more frequent and sensitive monitoring. METHODS: we compared the agreement
      between 17alpha-hydroxyprogesterone (17-OHP) and androstenedione (D4A) levels
      determined from DBS samples and concurrently collected serum samples. Blood was
      drawn from 9 congenital adrenal hyperplasia patients every 4 h over a 24-hour
      period. Serum and DBS steroid levels were measured by liquid chromatography
      tandem mass spectrometry. RESULTS: DBS determinations of 17-OHP overestimated
      corresponding serum levels (mean difference 1.67 ng/ml), and underestimated D4A
      serum levels (mean difference 0.84 ng/ml). However, the DBS assay yielded
      excellent agreement (97%) with serum 17-OHP, but did considerably poorer for D4A
      (31%). CONCLUSIONS: our results indicate an excellent agreement between DBS and
      serum 17-OHP measurements to identify the peaks and troughs associated with an
      individual's circadian pattern. Larger-scale studies are required to evaluate the
      utility of DBS for home monitoring and to determine if more frequent monitoring
      leads to improved clinical outcomes.

PMID- 20798479
TI  - Progenitor radial cells and neurogenesis in pejerrey fish forebrain.
AB  - The central nervous system of adult teleost fish is peculiar because of the
      following features: (1) the persistence of radial glial cells, (2) an important
      neurogenic activity and (3) a high aromatase expression by radial cells. In this
      study, the proliferative zones of the forebrain were described using
      bromodeoxyuridine (BrdU) treatment in the brain of the pejerrey, an
      Acanthopterygian teleost fish. These cells were shown to have morphological and
      immunoreactive characteristics of radial cells and to express aromatase. Three
      different progenitor populations were identified based on the mobility and
      proliferation capacity 6 weeks after BrdU treatment: transit amplifying
      progenitors, slowly proliferating stem cells, and cells remaining in the
      proliferative zones showing no signs of mitotic activity. The proliferative cells
      were always located in the ventricular zone and were never observed in the brain
      parenchyma; however, 3 weeks later they were found away from these proliferative
      zones and displayed acetylated tubulin immunoreactivity. Other BrdU-positive
      cells showed astrocyte morphology and were immunoreactive to the S100 glial
      marker. These results show that in this fish, radial cells are true progenitors
      generating neurons and possibly astrocytes.

PMID- 20798480
TI  - M1 protein-dependent intracellular trafficking promotes persistence and
      replication of Streptococcus pyogenes in macrophages.
AB  - Streptococcus pyogenes is an important human pathogen that causes a variety of
      diseases including life-threatening invasive diseases, such as toxic shock and
      deep tissue infections. Although S. pyogenes are classically considered
      extracellular pathogens, a clinical significance of an intracellular source has
      been emphasized. In patients with deep tissue infections, an intracellular
      reservoir of S. pyogenes within macrophages was shown to contribute to prolonged
      bacterial persistence. Here we demonstrate that intracellular survival of S.
      pyogenes in macrophages is associated with an M1 protein-dependent intracellular
      trafficking in the phagosomal-lysosomal pathway, which results in impaired fusion
      with lysosomes. The phagocytic vacuoles harbouring M1 protein-expressing bacteria
      not only served as a safe haven for the bacteria, but also as a replicating
      niche. An M1 protein-dependent modulation of macrophages was further supported by
      differences in NF-kappaB signalling between cells infected with either the wild
      type or M1 protein-deficient strains, thereby indicating a suppressed
      inflammatory response when M1 protein was involved. Evidence of egress of
      bacteria out of their host cell and subsequent re-infection of new cells
      emphasize the importance of intracellular bacteria as a reservoir for
      dissemination of infection and continued tissue injury.

PMID- 20798481
TI  - Mitochondrial function and insulin resistance during aging: a mini-review.
AB  - BACKGROUND: Insulin resistance, i.e. impaired insulin sensitivity, and type 2
      diabetes are more prevalent in elderly humans. Both conditions relate to lower
      aerobic performance and increased body fatness, which have been linked to reduced
      mitochondrial oxidative capacity. Thus, lower insulin sensitivity in the elderly
      could result from age-related diminished energy metabolism or from lifestyle
      related abnormalities. OBJECTIVE: This review addresses the question whether
      insulin sensitivity and mitochondrial oxidative capacity are independently
      affected during aging and type 2 diabetes. METHODS: Only studies were analyzed
      which included elderly persons and employed state-of-the-art methodology to
      assess insulin sensitivity and oxidative capacity, e.g. electron microscopic
      imaging, in vivo magnetic resonance spectroscopy or ex vivo high-resolution
      respirometry. RESULTS: Humans with or at risk of type 2 diabetes frequently
      exhibit insulin resistance along with structural and functional abnormalities of
      muscular mitochondria. Low mitochondrial oxidative capacity causes muscular fat
      accumulation, which impedes insulin signaling via lipid intermediates, in turn
      affecting oxidative capacity. However, insulin sensitivity is not generally
      reduced with age, when groups are carefully matched for physical activity and
      body fatness. Moreover, lifestyle intervention studies revealed discordant
      responses of mitochondrial oxidative capacity and insulin sensitivity.
      CONCLUSIONS: In the elderly, low mitochondrial oxidative capacity likely results
      from age-related effects acquired during life span. Insulin resistance occurs
      independently of age mostly due to unhealthy lifestyle on top of genetic
      predisposition. Thus, insulin sensitivity and mitochondrial function may not be
      causally related, but mutually amplify each other during aging.

PMID- 20798482
TI  - Psychometric properties of the PAT: an assessment tool for ADL performance of
      older people living in residential homes.
AB  - BACKGROUND: As the world population ages, the number of people with diminished
      performance on the Activities of Daily Living (ADL) increases. A reliable and
      valid measure needs to be developed to determine the effects of interventions
      focused at increasing self-care abilities. We developed the Performance ADL Test
      (PAT) for this purpose. OBJECTIVE: The aim of this study was to investigate the
      reliability and validity of the PAT in older people living in residential homes.
      METHODS: The PAT contains 16 test items, covering the entire range of Basic ADL
      and Instrumental ADL performance in elderly people. For this assessment, 40 older
      people (mean age of 85 +/- 7.5 years) participated. All 40 subjects lived in
      residential institutions in the Netherlands, were able to walk at least 10 m,
      could understand instructions spoken in Dutch, and had no cognitive impairment.
      During the first test session, subjects completed the PAT, the Groningen Activity
      Restriction Scale (GARS), and performance-based physical fitness tests. Two weeks
      later, subjects were retested on the PAT. RESULTS: Factor analysis revealed three
      subscales: Organization of Performance, Gross Motor Function, and Fine Motor
      Function. Internal consistency (Cronbach's alpha) of all scales and subscales
      ranged from 0.731 to 0.881. Test-retest reliability (intraclass correlation)
      ranged from 0.316 to 0.950. Paired sample t-tests revealed no significant
      differences between subject performance obtained during the two test periods.
      Pearson's correlations between the PAT and the GARS ranged from 0.490 to 0.831,
      and between the PAT and the fitness tests from 0.317 to 0.781. CONCLUSION:
      Although the number of participants was limited (n = 40), the PAT seems to be a
      useful instrument for assessing ADL performance in older people living in
      residential homes. In general, internal consistency, test-retest reliability, and
      validity were satisfactory.

PMID- 20798483
TI  - First-trimester prediction of macrosomia.
AB  - OBJECTIVE: To determine if combinations of maternal characteristics and
      measurements of parameters used in screening for aneuploidies at 11-13 weeks
      provide significant prediction of macrosomia. METHOD: Maternal characteristics,
      fetal nuchal translucency (NT), free beta-human chorionic gonadotrophin (beta
      hCG) and pregnancy-associated plasma protein-A (PAPP-A) were recorded at 11(+0)
      13(+6) weeks in 36,743 singleton pregnancies. Regression analysis was used to
      determine if in predicting macrosomia significant contributions are provided by
      maternal factors, fetal NT, free beta-hCG and PAPP-A. RESULTS: The risk for
      macrosomia increased with maternal weight and height and was higher in parous
      women with previous delivery of a macrosomic baby and in those with diabetes
      mellitus; the risk was lower in women of African and South Asian racial origins,
      in cigarette smokers and in those with chronic hypertension. In the macrosomic
      group compared to the unaffected group there were higher Delta-NT (0.167 vs.
      0.116 mm), free beta-hCG (1.010 vs. 0.964 MoM) and PAPP-A (1.103 vs. 1.003 MoM).
      Prediction of macrosomia provided by maternal factors was significantly improved
      by fetal NT, free beta-hCG and PAPP-A (34.4 vs. 33.1% at a false-positive rate of
      10%). CONCLUSION: Prediction of macrosomia is provided in the first trimester of
      pregnancy by a combination of maternal characteristics and measurements of
      parameters used in screening for aneuploidies.

PMID- 20798484
TI  - Drug rash with eosinophilia and systemic symptoms due to telaprevir.
AB  - We report a case of drug rash with eosinophilia and systemic symptoms (DRESS) due
      to telaprevir (VX-950), a specific inhibitor of the hepatitis C virus (HCV)
      serine protease. A 57-year-old woman with chronic hepatitis C was included in a
      phase 2 rollover study of VX-950. She received VX-950 in combination with
      pegylated interferon alfa-2a and ribavirin. Six weeks later, she developed a
      generalized pruritic maculopapular exanthema with malaise, fever, dyspnoea and
      lymph node swelling. She had an eosinophilia (up to 2.7 * 109 cells/l), large
      activated lymphocytes and increased concentrations of aminotransferases.
      Histological examination of a cutaneous biopsy was consistent with a drug rash
      reaction. The HCV treatment was stopped, and she was treated with topical and
      oral steroids. Cutaneous and systemic symptoms disappeared within 1 month.
      Telaprevir was considered the culprit drug. We report to our knowledge the first
      case of DRESS syndrome due to telaprevir. The safety data of telaprevir is
      derived mainly from the PROVE1, PROVE2 and PROVE3 studies. They showed a high
      frequency of cutaneous side effects reported under the imprecise terms of
      pruritus and rash, leading to an increased rate of treatment discontinuation.
      Telaprevir, due to its efficacy, is probably on the way to obtaining regulatory
      approval in the near future. It is therefore important to be aware of the high
      incidence of cutaneous side effects and better describe them. Our observation
      suggests that potentially severe hypersensitivity reactions may belong to the
      spectrum of rashes induced by this drug.

PMID- 20798485
TI  - Trigeminal and spinal dorsal horn (dis)continuity and avian evolution.
AB  - The organization of the dorsal horn in the avian spinal cord differs in different
      species. For instance, in pigeons and doves, cranes, cuckoos, songbirds, ratites
      and tinamous, the dorsal horn is organized in laminar fashion, such that laminae
      II and III are sandwiched between lamina I dorsally and lamina IV ventrally, as
      they are in mammals and other nonavian amniotes. In most other avian species,
      including chickens, however, the organization of the dorsal horn is not strictly
      laminar, in that the structures homologous to laminae II and III lie side by side
      rather than in dorsoventral order. Because spinal and trigeminal dorsal horns are
      generally thought to be continuous, the question arises as to the organization of
      the trigeminal dorsal horn in these species. We examined this question in
      chickens, first by defining II and III of trigeminal and spinal dorsal horns
      using calcium-binding protein immunohistochemistry, and second by determining the
      caudal extent of the projections of the three branches of the trigeminal nerve
      using injections of cholera toxin B chain. It was found (1) that the trigeminal
      dorsal horn and the spinal dorsal horn of the first 2 cervical segments are
      organized in laminar fashion, but further caudally, II and III in the spinal
      dorsal horn gradually come to be arranged side by side and (2) that the
      descending trigeminal tract terminates no further caudal than the 3rd spinal
      segment. Therefore, unlike spinal nerves, trigeminal nerve branches do not
      project to II and III, once these cease to be organized in laminar fashion. These
      findings imply some kind or organizational discontinuity of trigeminal and spinal
      dorsal horns in the chicken and perhaps in other species with a side-by-side
      arrangement of II and III. It has also been suggested that the condition in which
      the spinal dorsal horn structures homologous to laminae II and II lie side by
      side may define a novel clade of birds. This suggestion was reexamined within the
      context of a modern phylogenetic framework based on 32 kb of nuclear DNA, and
      using a parsimony reconstruction of dorsal horn character states. The original
      suggestion of a novel clade was not supported. Instead, it appears that the side
      by-side condition evolved very early in the radiation of Aves and that
      independent reversion to a laminar dorsal horn condition has evolved at least 4-5
      times.

PMID- 20798486
TI  - Chromosome mapping of retrotransposable elements Rex1 and Rex3 in three fish
      species in the subfamily Hypoptopomatinae (Teleostei, Siluriformes,
      Loricariidae).
AB  - Transposons and retrotransposons represent a great portion of the eukaryotic
      genome. These repeated elements can be defined as genetic entities capable of
      self-inserting into different positions within the genome modifying the functions
      of the genes with which they are associated. The purpose of the present work was
      to isolate, identify, and map the sequences of Rex1 and Rex3 transposable
      elements present in the genomes of fishes of the family Loricariidae. The
      retrotransposable elements were identified through amplification with Rex1 and
      Rex3 primers, and the nucleotide composition of the retrotransposons was
      determined by automatic sequencing. In all the species analyzed it was possible
      to isolate Rex1 partial sequences from 520 to 563 bp in size and Rex3 partial
      sequences from 407 to 454 bp in size. Comparisons with the available literature
      showed that Loricariidae retrotransposons Rex1 and Rex3 have a high sequence
      similarity to putative homologous genes in different fish orders. Fluorescence in
      situ hybridization experiments conducted in 3 species, Hisonotus leucofrenatus,
      Pseudotocinclus tietensis, and Parotocinclus maculicauda, using the
      retrotransposable elements isolated for each species as probes, revealed that
      Rex1 and Rex3 share a similar dispersion pattern and are both found on all
      chromosomes of the 3 species organized in small clusters and dispersed on all the
      chromosomes, including euchromatic and heterochromatic regions, although a larger
      concentration was observed in the heterochromatic regions of H. leucofrenatus.
      The data found in the present study contradict much of the literature that
      substantiates that the retrotranspon elements are preferentially accumulated in
      the heterochromatin regions in fishes.

PMID- 20798487
TI  - Level of heat shock proteins decreases in individuals carrying B-chromosomes in
      the grasshopper Eyprepocnemis plorans.
AB  - We analyzed the effect of B-chromosome presence on expression level of heat shock
      protein 70 (Hsp70) in cerebral ganglion and gonad in both males and females of
      the grasshopper Eyprepocnemis plorans. Two natural Spanish populations, Salobrena
      (Granada) and Torrox (Malaga) were assayed, the former harbouring a neutralized
      (non-driving) B-chromosome (B(2)) and the latter a parasitic (driving) B
      chromosome (B(24)). The analysis was performed by Western blotting,
      immunostaining and densitometric measuring expression level of the Hsp70 family
      in adult individuals. The results showed that Hsp70 levels of testis were
      significantly higher in Salobrena than Torrox, and were significantly lower in
      testes of B-carrying males from both populations. A similar effect was observed
      in the ovary of females from Torrox. No effect was, however, observed in cerebral
      ganglia in any sex or population. B-chromosome effects in Torrox showed a dose
      dependent pattern. The results point to an interesting interaction between B
      chromosome and stress protein expression in reproductive tissue.

PMID- 20798489
TI  - Secondary erythrocytosis caused by hemoglobin Tak/(deltabeta)0-thalassemia
      syndrome.
AB  - Secondary erythrocytosis may arise from several causes, but an association with
      oxygen transport is rare. We describe for the first time a form of secondary
      erythrocytosis caused by compound heterozygosity for hemoglobin (Hb) Tak and
      (deltabeta)(0)-thalassemia found in an adult Thai individual. The patient had
      marked erythrocytosis and microcytosis with increased Hb and hematocrit values.
      Hb analyses using the Hb Gold Analyzer showed Hb A2 (72.5%) and Hb F (30.0%)
      without Hb A while the capillary electrophoresis revealed 2.3% Hb A2 and a major
      peak of Hb F (91.2%). Further molecular investigation identified that he was in
      fact a compound heterozygote for Hb Tak and deletional (deltabeta)(0)
      thalassemia. Hematological parameters of the patient were compared with those
      observed for a Thai boy who demonstrated features of erythrocytosis and
      microcytosis caused by homozygous Hb Tak with alpha(+)-thalassemia and with those
      of pure carriers of Hb Tak and (deltabeta)(0)-thalassemia in our series. This
      report confirms the importance of both Hb and molecular investigations for the
      assessment of genotype/phenotype correlation and the appropriate management of
      the patients.

PMID- 20798488
TI  - Leptin responsiveness of mice deficient in corticotrophin-releasing hormone
      receptor type 2.
AB  - Leptin acts centrally to inhibit food intake and increase energy expenditure.
      Corticotrophin-releasing hormone (CRH) is one of the neuropeptides that may
      contribute to leptin-induced hypophagia and thermogenesis. Acute leptin
      administration increases CRH mRNA expression in the paraventricular nucleus of
      the hypothalamus and CRH receptor type 2 (CRHR2) expression in the ventromedial
      nucleus of the hypothalamus. Studies described here used male and female CRHR2
      knockout (KO) mice and wild-type (WT) controls to test the importance of CRHR2 in
      mediating the effects of leptin on food intake, weight gain and body composition.
      Peripheral injections of 0.5 mg/kg leptin for 3 days inhibited food intake in
      female WT and male KO mice, but inhibited weight gain in female KO and male WT
      mice suggesting an important role for thermogenesis in mediating weight loss. A
      single third ventricle injection of 1 MUg leptin inhibited 12 h food intake of
      all mice, 36 h cumulative intake of KO mice and weight loss in WT and KO female
      and WT male mice. A 12-day peripheral infusion of 10 MUg leptin/day had no effect
      on food intake of any group, but significantly reduced carcass fat and protein
      content of all mice. These results indicate that CRHR2 are not essential for the
      effects of leptin on food intake, body weight or body composition. Leptin
      response seems to be determined by a combination of mouse gender and genotype,
      but CRHR2 KO mice may have an extended response to central leptin injections
      compared with their WT controls.

PMID- 20798490
TI  - Sevoflurane protects against acute kidney injury in a small-size liver
      transplantation model.
AB  - BACKGROUND: Living donor liver transplantation (LDLT) patients run the risk of
      developing acute kidney injury (AKI) and subsequent chronic kidney disease,
      affecting morbidity and mortality. Sevoflurane has anti-inflammation properties,
      and renal ischemia/reperfusion under sevoflurane anesthesia resulted in drastic
      improvements in renal function. Extrahepatic metabolism of sevoflurane has been
      reported in patients undergoing liver transplantation, and might lead to
      nephrotoxicity. However, whether sevoflurane anesthesia is safe with regard to
      renal function in small-size liver transplantation needs further investigation.
      As neutrophil gelatinase-associated lipocalin (NGAL) is an early predictive
      biomarker of AKI, we looked at the renal effects of sevoflurane in a rat liver
      transplantation model using small-for-size grafts to investigate the changes of
      NGAL level and kidney histology. METHODS: Sixty male Sprague-Dawley rats were
      randomly divided into 2 groups after 50% size liver transplantation. Rats were
      anesthetized with chloral hydrate or with sevoflurane and subjected to liver
      transplantation. Twelve rats in each group were used for the survival study and 6
      rats were used for the hemodynamic study. Six rats in each group were sacrificed
      2 or 24 h after reperfusion. We harvested kidneys and serum for further analysis,
      including histological and functional parameters; TNF-alpha, IL-6 and NGAL
      immunoassay; expressions of myeloperoxidase (MPO) activity; and NF-kappaB in
      renal tissues. RESULTS: Rats in the sevoflurane group had significantly lower Scr
      24 h after reperfusion compared with those in the chloral hydrate group. Rats in
      the sevoflurane group demonstrated significantly reduced NGAL concentrations
      compared with rats in the chloral hydrate group 2 h after reperfusion. Epithelial
      necrosis in the chloral hydrate group (3.2 +/- 0.8) was greater than that in the
      sevoflurane group (1.5 +/- 1.1; p < 0.05). Sevoflurane anesthesia resulted in
      significantly lower plasma TNF-alpha and IL-6 concentrations and reduced MPO
      concentrations 2 h after reperfusion (p < 0.05). NF-kappaB protein levels 2 h
      after reperfusion increased by at least 110% in the chloral hydrate group
      relative to the sevoflurane group 2 h after reperfusion (p < 0.05). However, the
      urine inorganic fluoride concentrations increased significantly (p < 0.001) 2 h
      after reperfusion in the sevoflurane group (6.1 +/- 1.5 MUmol.l-1) compared with
      the chloral hydrate group. CONCLUSIONS: Sevoflurane anesthesia can attenuate
      renal injury and modulate inflammatory cascades in small-size liver
      transplantation using rat models.

PMID- 20798491
TI  - Towards preventing noncommunicable diseases: The New WHO Global Noncommunicable
      Disease Network.

PMID- 20798492
TI  - Role of genetic and acquired prothrombotic risk factors in genesis of sudden
      sensorineural hearing loss.
AB  - The methylenetetrahydrofolate reductase C677T mutation, factor V G1691A (factor V
      Leiden) mutation, prothrombin G20210A mutation and 8 other laboratory values
      associated with increased thrombotic risk were analyzed in 40 patients with
      sudden sensorineural hearing loss (SSHL). The results were compared with those
      obtained from 120 controls not affected by SSHL. We found a statistically
      significant higher frequency of hyperhomocysteinemia in the SSHL group compared
      with controls, and that this was also associated with the presence of
      homozygosity for the MTHFR C677T mutation. The study results suggest that SSHL
      might be caused, among other factors, by a combination of these 2 variables. We
      suggest that this analysis of the MTHFR C677T mutation should be further
      investigated to establish the etiology of SSHL, and that the same analysis should
      be taken into account in those patients with high levels of homocysteine.

PMID- 20798493
TI  - Sudden death in hemodialysis: an update.
AB  - Cardiovascular disease including sudden death, myocardial infarction, cardiac
      arrest, malignant arrhythmias and other cardiac causes is the major cause of
      death accounting for 43% of all-cause mortality among hemodialysis patients. In
      addition to increased traditional risk factors, hemodialysis patients also have a
      number of nontraditional cardiovascular risk factors, which may play a prominent
      role in the development of sudden death such as left ventricular hypertrophy,
      coronary artery disease, rapid electrolyte shifts, QT dispersion, sympathetic
      overactivity, calcium-phosphate deposition. The purpose of the present review was
      to critically review the current literature to summarize the following aspects:
      (1) the pathophysiological mechanism responsible for sudden death in hemodialysis
      patients, and (2) the prevention and management of sudden death in hemodialysis
      patients.

PMID- 20798494
TI  - Association between tumor necrosis factor-alpha (-308G->A and -238G->A)
      polymorphisms and homocysteine levels in patients with ischemic strokes and
      silent brain infarctions.
AB  - BACKGROUND AND PURPOSE: The aims of this study were to evaluate the role of tumor
      necrosis factor-alpha (TNF-alpha) polymorphisms in patients susceptible to
      ischemic stroke and silent brain infarction (SBI), and to determine the
      relationship between TNF-alpha polymorphisms and plasma total homocysteine (tHcy)
      levels. METHODS: We studied 237 patients with ischemic stroke, 257 patients with
      SBIs, and 216 control subjects. For control subjects, we selected healthy
      individuals matched for gender and age from those individuals who came to our
      hospital for health examinations. The TNF-alpha-308G->A and -238G->A genotypes
      were determined by the polymerase chain reaction-restriction fragment length
      polymorphism method. RESULTS: The frequency of the TNF-alpha-308G->A polymorphism
      was significantly different between the patients with ischemic stroke and the
      control group (GG vs. GA+AA; adjusted odds ratio, AOR, 0.50; 95% CI 0.255-0.989).
      By subgroup analysis, when tHcy levels were stratified into high (>10.80
      MUmol/l), moderate (8.21-10.80 MUmol/l), and low levels (<8.21 MUmol/l), the
      frequency of the TNF-alpha-308GA+AA genotype in the highest tertile group was
      higher than in the lowest tertile group (AOR 2.46; 95% CI 1.063-5.699). However,
      the relationship between SBI susceptibility and polymorphisms of TNF-alpha was
      not established. The tHcy levels were significantly and inversely correlated with
      folate levels in the TNF-alpha-308GG and TNF-alpha-238GG genotypes in the
      ischemic stroke, SBI, and control groups (p< 0.05). CONCLUSIONS: Our results
      suggest that the TNF-alpha-308G->A polymorphism is responsible for susceptibility
      to ischemic stroke and is associated with high tHcy levels in Koreans.

PMID- 20798495
TI  - Induced pluripotent stem cells: a new approach for physiological research.
AB  - The generation of induced pluripotent stem (iPS) cells by controlled delivery of
      reprogramming factors enables the derivation of pluripotent cells from a variety
      of somatic cell types. Patient-tailored iPS cells remove the major roadblock of
      immune rejection for clinical applications associated with the use of human
      embryonic stem (hES) cells. Beside therapeutic issues, iPS cell technology opens
      the door for broader research on human pluripotent cells because ethical
      limitations are lifted with iPS cells compared to hES cells. Scientists are now
      able to generate iPS cells for disease modelling and use them in basic research
      of physiological and pathophysiological models. In this concise review, we
      discuss the state of the art in the field of iPS cell induction by cell fusion or
      defined factors. Techniques to derive pluripotent cells from somatic sources are
      introduced and discussed, as well as some biological factors that influence the
      generation of iPS cells. We compare ES and iPS cells to answer the question
      whether these cells are identical, and we finish with an outlook on clinical
      research with iPS cells with a focus on cardiovascular medicine.

PMID- 20798496
TI  - Higher concentrations of extracellular ATP suppress proliferation of Caco-2 human
      colonic cancer cells via an unknown receptor involving PKC inhibition.
AB  - BACKGROUND/AIMS: Adenosine 5'-triphosphate (ATP) mediates a variety of signal
      transductions via ATP receptors such as P2X and P2Y receptors. The present study
      aimed at understanding the mechanism underlying extracellular ATP-induced
      suppression of Caco-2 human colonic cancer cell proliferation. METHODS: Caco-2
      cells were cultured. To examine cell viability and cell cycling, 3-(4,5-dimethyl
      2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, fluorescent
      cytochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling (TUNEL) assay, and flow cytometry were carried out. To see mRNA
      expression of ATP receptors, reverse transcription-polymerase chain reaction (RT
      PCR) was performed. To examine PKC activity and mitogen-activated protein (MAP)
      kinase activity, in situ PKC assay and Western blotting using an anti
      extracellular signal-regulated kinase 1 (ERK1)-antibody and an anti-phospho-ERK
      antibody were carried out. RESULTS: Extracellular ATP or the unhydrolyzed ATP
      analogue 5'-adenylyimido-diphosphate (AMP-PNP) reduced Caco-2 cell viability in a
      concentration (10 microM-10 mM)-dependent manner at 48-h treatment, and the
      effect was not affected by caspase inhibitors. Caco-2 cells were little reactive
      to propidium iodide and Hoechst 33342 or little positive to TUNEL after 48-h
      treatment with ATP (1 mM). In the flow cytometry, 48-h treatment with ATP (1 mM)
      arrested cell cycling at the S phase in Caco-2 cells. P(2) purinoceptor agonists
      reduced Caco-2 cell viability with the order of potency: 2-methylthio
      ATP>UTP>beta, gamma-methylene ATP, and the ATP effect was partially inhibited by
      suramin, a non-selective inhibitor of P(2) purinoceptors. The PKC inhibitor
      GF109203X or the MAP kinase kinase inhibitor PD98059 reduced Caco-2 cell
      viability to an extent similar to that achieved by ATP (1 mM), and no further
      reduction was obtained with co-treatment with ATP. ATP and its ATP analogues such
      as AMP-PNP and ATPgammaS, at higher concentrations (1-10 mM), inhibited PKC
      activation in Caco-2 cells in a fashion that mimics the effect of GF109203X, but
      PD98059 exhibited no effect on PKC activation. The inhibitory effect of ATP on
      PKC activation was not found with SK-N-SH cells, a human neuroblastoma cell line,
      but the cells expressed all the mRNAs for P2X and P2Y receptors that Caco-2 cells
      did. ATP (10 mM) or GF109203X inhibited activation of ERK, a MAP kinase, in Caco
      2 cells. CONCLUSION: Extracellular ATP, at higher concentrations, suppresses Caco
      2 cell proliferation at the S phase of cell cycling by inhibiting PKC, possibly
      as mediated via an unknown ATP receptor, followed by MAP kinase.

PMID- 20798497
TI  - GH3B6 pituitary tumor cell proliferation is mediated by PKCalpha and PKCepsilon
      via ERK 1/2-dependent pathway.
AB  - BACKGROUND: In this report, we explored the role of PKCalpha and PKCe as
      mediators of phorbol 12-myristate13-acetate (PMA)-induced proliferation in
      pituitary tumor GH3B6 cells, and determined if the ERK1/2 and Akt pathways were
      activated. METHODS: The GH3B6 cell proliferation was estimated by BrdU
      incorporation and the cell cycle progression by flow cytometric cell cycle
      analysis. We determined the expression of PKCalpha and PKCe in membrane and
      cytosolic fractions by western blotting. The subcellular redistribution of both
      PKC isozymes was analyzed by confocal microscopy. RESULTS: Incubation with PMA
      for 15 min stimulated PKCalpha and PKCe activation, which was correlated with the
      phosphorylation of ERK1/2 but not Akt. The activation of both these PKC isozymes
      was closely associated with the stimulation of proliferation and the cell cycle
      progression induced by PMA in GH3B6 cells, an effect that was blocked by the
      inhibitors of PKCalpha (Go6976) and PKCe (eV1-2). In addition, the pretreatment
      with the inhibitor of ERK1/2 (PD98059) prevented the mitogenic activity induced
      by treatment with PMA for 15 min. CONCLUSION: We demonstrated that the activation
      of PKCalpha and PKCe by phorbol ester in tumor pituitary GH3B6 cells led to cell
      proliferation and cell cycle progression, effects that involved ERK1/2
      activation.

PMID- 20798498
TI  - Phosphoglycerate kinase 1 promoting tumor progression and metastasis in gastric
      cancer - detected in a tumor mouse model using positron emission
      tomography/magnetic resonance imaging.
AB  - BACKGROUND/AIMS: Tumor dissemination is frequent in gastric cancer and implies a
      poor prognosis. Cure is only achievable provided an accurate staging is performed
      at primary diagnosis. In previous studies we were able to show a relevant impact
      of increased phosphoglycerate kinase 1 expression (PGK1; a glycolytic enzyme) on
      invasive properties of gastric cancer in-vivo and in-vitro. Thus the aim of the
      present study was to evaluate the effect of enhanced PGK1 expression in gastric
      cancer employing magnetic resonance (MR)-imaging combined with positron emission
      tomography (PET), a recently emerging new high resolution imaging technique in a
      mouse model. METHODS: A metastatic nude mouse model simulating human gastric
      cancer behavior by orthotopic tumor implantation was established. Mice were
      divided into one control group (n=5) and two experimental groups (n=30) divided
      by half in animals baring tumors from MKN45-cells and MKN45-cells with plasmid
      mediated overexpression of PGK1. In the course of tumor growth MR-imaging and
      PET/MRI fusion was performed. Successively experimental animals were examined
      macroscopically and histopathologically regarding growth, metastasis and PGK1
      expression. RESULTS: Elevated PGK1 expression increased invasive and metastatic
      behavior of implanted gastric tumors significantly. MR/PET- imaging results in
      vivoand subsequent ex-vivo findings concerning tumor growth and metastasis
      correlated excellently and could be underlined by concordant immuohistochemical
      PGK1 staining. CONCLUSION: Consistent in-vivo findings suggest that PGK1 might be
      crucially involved in gastric malignancy regarding growth and metastasis, which
      was also underlined by novel imaging techniques. Thus, PGK1 may be exploited as a
      prognostic marker and/or be of potential therapeutic value preventing malignant
      dissemination.

PMID- 20798499
TI  - Circadian expression of clock- and tumor suppressor genes in human oral mucosa.
AB  - PURPOSE: Circadian rhythms are daily oscillations of multiple biological
      processes driven by endogenous clocks. Imbalance of these rhythms has been
      associated with cancerogenesis in humans. To further elucidate the role circadian
      clocks have in cellular growth control, tumor suppression and cancer treatment,
      it is revealing to know how clock genes and clock-controlled genes are regulated
      in healthy humans. MATERIALS AND METHODS: Therefore comparative microarray
      analyses were conducted investigating the relative mRNA expression of clock genes
      throughout a 24-hour period in cell samples obtained from oral mucosa of eight
      healthy diurnally active male study participants. Differentially expressed
      selected genes of interest were additionally evaluated using qRT-PCR. RESULTS:
      Microarray analysis revealed 33 significant differentially regulated clock genes
      and clock- controlled genes, throughout a one day period (6.00h, 12.00h, 18.00h,
      24.00h). Hereof were 16 clock genes and 17 clock- controlled genes including
      tumor suppressor- and oncogenes. qRT-PCR of selected genes of interest, such as
      hPER2, hCRY1, hBMAL1, hCCRN4L and hSMAD5 revealed significant circadian
      regulations. CONCLUSION: Our study revealed a proper circadian regulation profile
      of several clock- and tumor suppressor genes at defined points in time in the
      participants studied. These findings could provide important information
      regarding genes displaying the same expression profile in the gastrointestinal
      tract amounting to a physiological expression profile of healthy humans. In the
      future asynchronous regulations of those genes might be an additional assistant
      method to detect derivations distinguishing normal from malignant tissue or
      assessing risk factors for cancer.

PMID- 20798500
TI  - Partial inactivation of cardiac 14-3-3 protein in vivo elicits endoplasmic
      reticulum stress (ERS) and activates ERS-initiated apoptosis in ERS-induced mice.
AB  - BACKGROUND/AIMS: Excessive endoplasmic reticulum stress (ERS) triggers apoptosis
      in various conditions including diabetic cardiomyopathy and pressure overload
      induced cardiac hypertrophy and heart failure. The primary function of 14-3-3
      protein is to inhibit apoptosis, but the roles of this protein in protecting
      against cardiac ERS and apoptosis are largely unknown. METHODS: We investigated
      the roles of 14-3-3 protein in vivo during cardiac ERS and apoptosis induced by
      pressure overload or thapsigargin injection using transgenic (TG) mice that
      showed cardiac-specific expression of dominant negative (DN) 14-3-3eta. RESULTS:
      Cardiac positive apoptotic cells and the expression of glucose-regulated protein
      (GRP)78, inositol-requiring enzyme (Ire)1alpha, tumor necrosis factor receptor
      (TNFR)-associated factor (TRAF)2, CCAAT/enhancer binding protein homology protein
      (CHOP), caspase-12, and cleaved caspase-12 protein were significantly increased
      in the pressure-overload induced DN 14-3-3eta mice compared with that in the WT
      mice. Furthermore, thapsigargin injection significantly increased the expression
      of GRP78 and TRAF2 expression in DN 14-3-3eta mice compared with that in the WT
      mice. CONCLUSION: The enhancement of 14-3-3 protein may provide a novel
      protective therapy against cardiac ERS and ERS-initiated apoptosis, at least in
      part, through the regulation of CHOP and caspase-12 via the Ire1alpha/TRAF2
      pathway.

PMID- 20798501
TI  - Growth/differentiation factor-5 induces osteogenic differentiation of human
      ligamentum flavum cells through activation of ERK1/2 and p38 MAPK.
AB  - Ossification of ligamentum flavum (OLF) is a pathological ectopic ossification in
      the spinal ligament, leading to spinal canal stenosis, but little was known about
      its pathogenesis. A previous study has found growth/differentiation factor (GDF)
      5 expression at ossified sites of the ligaments from OLF patients. This study
      aimed to investigate the osteogenic effects of GDF-5 on cultured human ligamentum
      flavum cells (LFCs). LFCs were isolated from human spinal ligamentum flavum, and
      treated with or without recombinant human (rh) GDF-5. Alkaline phosphatase (ALP)
      activity was measured. Expression of osteocalcin was assessed by reverse
      transcriptase-PCR, Western blotting and immunofluorescence. Matrix mineralization
      was assessed by alizarin red staining. Activation of mitogen-activated protein
      kinases (MAPK) ERK1/2, p38 and JNK were detected by Western blotting. We found
      that rhGDF-5 treatment increased ALP activity and osteocalcin expression in a
      time- and dose-dependent manner, and induced mineralized nodule form. In
      addition, rhGDF-5 challenge mediated the ERK1/2 and p38 activation but not JNK.
      Inhibiting this activation pharmacologically, using U0126, a ERK1/2 inhibitor, or
      SB203580, a p38 inhibitor, resulted in significantly lower ALP activity and
      osteocalcin protein expression. The present study shows that rhGDF-5 induces
      osteogenic differentiation of human LFCs through activation of ERK1/2 and p38
      MAPK. These findings give some new insight into the pathogenesis of OLF.

PMID- 20798502
TI  - Cannabinoid receptors are coupled to stimulation of insulin secretion from mouse
      MIN6 beta-cells.
AB  - Endocannabinoid lipids are known to exert orexigenic effects via central
      cannabinoid CB1 and CB2 receptors, which have also been identified in islet
      endocrine cells. However, there is no consensus on whether the receptors are
      expressed by beta-cells, nor what effect CB1 and CB2 receptor agonists have on
      insulin secretion. In the current study we have therefore used the mouse MIN6
      beta-cell line rather than primary islets, which are heterogeneous clusters of
      endocrine cells. Cannabinoid receptor and diacylglycerol lipase isoform mRNAs
      were detected in MIN6 cells by RT-PCR and immunocytochemistry was used to
      identify cannabinoid receptor expression by MIN6 cells. Changes in cyclic AMP and
      intracellular calcium were measured by immunoassay and microfluorimetry,
      respectively, and insulin secretion from perifused MIN6 pseudoislets was
      determined by radioimmunoassay. MIN6 beta-cells express the cannabinoid
      synthesising enzyme diacylglycerol lipase and CB1 and CB2 receptors, which are
      coupled to inhibition of beta-cell cyclic AMP generation and stimulation of
      intracellular calcium levels. Cannabinoid receptor activation with
      pharmacological agonists resulted in reversible elevations in insulin secretion
      at both 2 mM and 20 mM glucose. Synthesis of endocannabinoids by beta-cells may
      provide an additional mechanism for stimulation of insulin secretion through
      activation of beta-cell CB1 and/or CB2 cannabinoid receptors.

PMID- 20798503
TI  - Cell swelling-induced insulin secretion from INS-1E cells is inhibited by
      extracellular Ca2+ and is tetanus toxin resistant.
AB  - Cell swelling-induced insulin secretion represents an alternative pathway of
      stimulation of insulin secretion. INS-1E rat tumor beta cells do not release
      insulin in response to cell swelling in presence of Ca(2+) despite a good
      response to glucose challenge and appropriate increase in cell volume.
      Surprisingly, perifusion with Ca(2+)-depleted medium showed distinct secretory
      response of INS-1E cells to hypotonicity. Objective of this study was further
      characterization of the role of Ca(2+) in secretory process in INS-1 and INS-1E
      cell lines. Ca(2+) depleted hypotonic medium with 10 muM BAPTA/AM (intracellular
      chelator) induced insulin secretion from both types of cells. We demonstrated
      expression of L-type Ca(2+) channel Ca(v)1.2 and non-L-type Ca(2+) channels
      Ca(v)2.1 (P/Q-type), Ca(v)2.2 (N-type), and Ca(v)3.1 (T-type) in both cell lines.
      Inhibition of L type channel with nifedipine and/or P/Q type with omega-agatoxin
      IVA enabled distinct response to hypotonic medium also in INS-1E cells. Tetanus
      toxin (TeTx) in medium containing Ca(2+) and a group of calcium channel blockers
      inhibited hypotonicity-induced insulin secretion from INS-1 cells but not from
      INS-1E cells. CONCLUSION: Hypotonicity-induced insulin secretion from INS-1E
      cells is inhibited by extracellular Ca(2+), does not require intracellular Ca(2+)
      and is TeTx resistant.

PMID- 20798504
TI  - Mechanisms of hyposmotic volume regulation in isolated nematocytes of the
      anthozoan Aiptasia diaphana.
AB  - The nature and role of potassium (K) and water transport mediating hyposmotically
      induced regulatory volume decrease (RVD) were studied in nematocytes dissociated
      with 605 mM thiocyanate from acontia of the Anthozoan Aiptasia diaphana. Cell
      volume and hence RVD were calculated from the inverse ratios of the cross
      sectional areas of nematocytes (A/A(o)) measured before (A(o)) and after (A)
      challenge with 65% artificial sea water (ASW). To distinguish between K channels
      and K-Cl cotransport (KCC), external sodium (Na) and chloride (Cl) were replaced
      by K and nitrate (NO(3)), respectively. Inhibitors were added to identify K
      channels (barium, Ba), and putative kinase (N-ethylmaleimide, NEM) and
      phosphatase (okadaic acid, OA) regulation of KCC. In 65% NaCl ASW, nematocytes
      displayed a biphasic change in A/A(o), peaking within 4 min due to osmotic water
      entry and thereafter declining within 6 min due to RVD. Changing NaCl to KCl or
      NaNO(3) ASW did not affect the osmotic phase but attenuated RVD, consistent with
      K channel and KCC mechanisms. Ba (3 mM) inhibited RVD. NEM and OA, applied
      separately, inhibited the osmotic phase and muted RVD suggesting primary action
      on water transport (aquaporins). NEM and OA together reduced the peak A/A(o)
      ratio during the osmotic phase whereas RVD was inhibited when OA preceded NEM.
      Thus, both K channels and KCC partake in the nematocyte RVD, the extent of which
      is determined by functional thiols and dephosphorylation of putative aquaporins
      facilitating the preceding osmotic water shifts.

PMID- 20798505
TI  - Voltage-dependent potassium channels Kv1.3 and Kv1.5 in human fetus.
AB  - Voltage-dependent K(+) channels (Kv) control repolarization and membrane
      potential in electrically excitable cells. In addition, Kv channels are involved
      in the maintenance of vascular smooth muscle tone, insulin release, epithelial
      K(+) transport, cell proliferation and leukocyte activation. Kv1.3 and Kv1.5 are
      widely distributed throughout the body and are involved in a variety of
      physiological processes taking place in the immune system, brain and muscle.
      Since the developmental pattern of Kv channels has an essential role in the
      maturing human, we aimed to study Kv1.3 and Kv1.5 channels in 8-10 week human
      fetal tissues. We chose that gestational age because all organs are in place and
      the nervous system, although not fully developed. However, the human embryo is
      undergoing major changes, which will lead to a defined adult pattern. Our results
      indicated that numerous tissues expressed Kv1.3 and Kv1.5. While Kv1.3 overlapped
      with the central and peripheral nervous systems, Kv1.5 was mostly localized in
      the central nervous system. In addition, both channels were abundantly expressed
      in the hematopoietic fetal liver. Finally, Kv1.5 heavily stained skeletal muscle
      and heart, whereas Kv1.3 was slightly present. This is the first study to analyze
      Kv1.3 and Kv1.5 in human during the beginning of fetal development.

PMID- 20798506
TI  - Thyroid hormone beta receptor mutation causes renal dysfunction and impairment of
      ClC-2 chloride channel expression in mouse kidney.
AB  - BACKGROUND/AIMS: Mutations in the thyroid hormone receptor beta (TR-beta) gene
      result in resistance to thyroid hormone (RTH). Mutation Delta337T in the TR-beta
      gene has been shown to have the characteristics of RTH syndrome in mice. The aim
      of this work was to study the possible involvement of TR-beta receptor in thyroid
      modulation of ClC-2 in mouse kidney. METHODS: Expression of mouse (Delta337T and
      normal C57BL/6) renal RNA and protein expression were studied by reverse
      transcriptase-polymerase chain reaction and Western blot, respectively, in mice
      with hyper- or hypothyroidism. Renal function was studied by analysis of urinary
      electrolyte excretion. Studies of the ClC-2 promoter region were performed in
      immortalized renal proximal tubule (IRPT) cells. RESULTS: In RTH syndrome mice
      (Delta337T), renal dysfunction was found to be associated with changes in the
      fractional excretion of sodium (FE(Na)) and chloride (FE(Cl)). ClC-2 chloride
      channel mRNA and protein expression were found to be decreased by 40% in
      heterozygous and homozygous mutant mouse kidneys and high levels of plasma
      thyroid hormone were detected in both groups. Hypothyroidism induced by
      methimazole decreased the renal expression of ClC-2 in normal mice but not in
      Delta337T mutant mice. In in vitro studies performed on IRPT cells subjected to
      thyroid hormone treatment, the promoter region of the ClC-2 chloride channel was
      stimulated in a dose-dependent manner. CONCLUSIONS: This work emphasizes the
      importance of thyroid hormone in electrolyte handling along the nephron and
      suggests its participation in renal ClC-2 gene transcription via the TR-beta
      receptor pathway.

PMID- 20798507
TI  - The cytoprotective action of the potassium channel opener BMS-191095 in C2C12
      myoblasts is related to the modulation of calcium homeostasis.
AB  - BMS-191095 is an opener of the mitochondrial ATP-regulated potassium channel,
      which has been shown to provide cytoprotection in models of ischemia-reperfusion
      induced injury in various tissues. This study aimed at checking the protective
      action of BMS-191095 under the conditions of oxidative stress or disruption of
      intracellular calcium homeostasis. METHODS: The cytoprotective potential of BMS
      191095 was tested in C2C12 myoblasts injured by treatment with H(2)O(2) or
      calcium ionophore A23187. The influence of the opener on intracellular calcium
      levels, calpain activity and respiration rates were determined. RESULTS: BMS
      191095 protected myoblasts from calcium ionophore A23187-induced injury, but not
      from H H(2)O(2)-induced injury. A23187-mediated cell damage was also prevented by
      calpain inhibitor PD 150606. A23187 administration led to a transient increase in
      cytosolic calcium levels, concomitant activation of calpains and a decrease in
      state 3 respiration rates, indicating mitochondrial dysfunction. Co
      administration of BMS-191095 diminished calpain activation in A23187-treated
      cells but did not prevent mitochondrial damage. In the presence of BMS-191095,
      restoration of cytosolic calcium concentrations to basal levels after A23187
      treatment was considerably faster which may underly the reduced activation of
      calpains. CONCLUSION: The BMS-191095-mediated cytoprotection observed in C2C12
      myoblasts results probably from modulation of intracellular calcium transients
      leading to prevention of calpain activation.

PMID- 20798508
TI  - Auto-positive feedback regulation for nicotinic acetylcholine receptors by
      protein kinase C activation.
AB  - BACKGROUND/AIMS: Protein kinase C (PKC) is well-recognized to modify ligand-gated
      ion channels such as nicotinic ACh (nACh) receptors by phosphorylating the
      receptors. The aim of the present study was to obtain direct evidence for PKC
      activation through nACh receptors. METHODS: Two-electrode voltage-clamp was made
      to Xenopus oocytes expressing wild-type and mutant Torpedo nACh receptors.
      Western blotting using antibodies against phospho-serine and phospho-threonine
      was carried out in oocytes expressing Torpedo nACh receptors. In situ PKC
      activation was monitored in cultured rat skeletal muscle cells expressing nACh
      receptors. RESULTS: In the Xenopus oocyte expression systems, ACh-evoked whole
      cell membrane currents through wild-type Torpedo nACh receptors were depressed by
      GF109203X, a PKC inhibitor, while currents through mutant receptors lacking PKC
      phosphorylation sites was not affected. In the Western blot analysis, ACh
      produced immunoreactive bands against an anti-phospho-serine or an anti-phospho
      threonine antibody in oocytes expressing wild-type Torpedo nACh receptors, and
      those signals were attenuated by alpha-bungarotoxin, an inhibitor of nACh
      receptors, or GF109203X. In the in situ PKC assay using cultured rat muscle cells
      that expressed all the mRNAs for muscle nACh receptor subunits such as the alpha,
      beta, gamma, delta, and e subunit, ACh activated PKC in the presence of atropine,
      an inhibitor of muscarinic ACh receptors, and the activation was abolished by
      alpha-bungarotoxin or GF109203X. CONCLUSION: The results of the present study
      show that ACh activates PKC through nACh receptors and that in turn, activated
      PKC constantly enhances ACh receptor responses by phosphorylating the receptors.
      This may represent a new auto-positive feedback regulation for nACh receptors by
      PKC activation.

PMID- 20798509
TI  - Characterization of a plant glutamate receptor activity.
AB  - Bioinformatic approaches have allowed the identification of twenty genes, grouped
      into three subfamilies, encoding for homologues of animal ionotropic glutamate
      receptors (iGLRs) in the Arabidopsis thaliana model plant. Indirect evidence
      suggests that plant iGLRs function as non-selective cation channels. In the
      present work we provide biochemical and electrophysiological evidences for the
      chloroplast localization of glutamate receptor(s) of family 3 (iGLR3) in spinach.
      A specific antibody, recognizing putative receptors of family 3 locates iGLR3 to
      the inner envelope membrane of chloroplasts. In planar lipid bilayer experiments,
      purified inner envelope vesicles from spinach display a cation-selective
      electrophysiological activity which is inhibited by DNQX (6,7-dinitroquinoxaline
      2,3-dione), considered to act as an inhibitor on both animal and plant iGLRs.
      These results identify for the first time the intracellular localization of plant
      glutamate receptor(s) and a DNQX-sensitive, glutamate-gated activity at single
      channel level in native membrane with properties compatible with those predicted
      for plant glutamate receptors.

PMID- 20798510
TI  - Genes determining the course of virus persistence in the liver: lessons from
      murine infection with lymphocytic choriomeningitis virus.
AB  - More than 500 million people worldwide are persistently infected with either
      hepatitis B virus (HBV) or hepatitis C virus (HCV). Although both viruses are
      poorly cytopathic, persistent infection causes severe immunopathologic damage to
      liver tissue; histologically, such damage is characterized by fatty liver
      disease, liver fibrosis, and a higher likelihood of hepatocellular carcinoma.
      Virus-specific CD8+ T cells play a crucial role during infection with hepatitis
      viruses. On the one hand, rapid activation of CD8+ T cells can control the virus
      and therefore inhibit its persistence. On the other hand, once the virus persists
      in the liver, the chronic activation of virus-specific T cells leads to continued
      liver cell damage. This double-edged role of CD8+ T cells determines the final
      outcome of infection. In half of cases of human HCV infection, the virus
      persists; in the other half, the virus is controlled. Additional insights into
      the molecular mechanisms that determine the course of the disease may be gained
      from the study of appropriate murine models. This review discusses the
      similarities and differences between infection with lymphocytic choriomeningitis
      virus (LCMV) in mice and chronic infection with hepatitis virus in humans.

PMID- 20798511
TI  - Pressure activates Src-dependent FAK-Akt and ERK1/2 signaling pathways in rat
      hepatic stellate cells.
AB  - BACKGROUND AND AIMS: Hepatic fibrosis is associated with elevated sinusoidal
      pressure, which can be transmitted to the hepatic stellate cells (HSCs) in the
      perisinusoidal space of Disse. Here, we sought to determine the effects of
      pressure on cellular growth and Src-dependent signaling pathways in the rat HSCs.
      METHODS: Cultured rat HSCs were exposed to pressures (0 to 80 mmHg) by using a
      pressure-inducing apparatus. The proliferation of the cells was determined by a 5
      bromo-2'-deoxy-uridine (BrdU) incorporation assay. Reverse transcription-PCR and
      Western-blot analysis were used to examine the mRNA and protein levels of
      representative molecules in Src-dependent signaling pathways. RESULTS: Pressure
      at 10 to 20 mmHg applied to the HSCs over 1 h upregulated Brdu incorporation and
      expression of proliferating cell nuclear antigen (PCNA) and type I collagen,
      while a higher pressure of 40-80 mmHg did not have noticeable effect. The mRNA
      level of beta (3) integrin was increased by 1-h application of 5 to 20 mmHg.
      Immunoblot with phospho-specific antibodies demonstrated the phosphorylation of
      Src (Tyr418), focal adhesion kinase (FAK) (Tyr397), Akt (Ser473) and
      extracellular signal-regulated kinases 1 and 2 (ERK1/2) (Thr421/Ser424) was
      increased in response to 10-mmHg pressure. Herbimycin A, an inhibitor of Src
      phosphorylation, attenuated the pressure-induced HSC proliferation and
      phosphorylation of above-mentioned signaling molecules. CONCLUSION: Our data
      demonstrated that pressure alone induced HSC proliferation involving the
      activation of Src-dependent signaling pathways.

PMID- 20798512
TI  - Amino acid deprivation decreases intracellular levels of reactive oxygen species
      in hepatic stellate cells.
AB  - In eukaryotic cells amino acid deprivation triggers a response aimed to ensure
      cell survival in stress conditions. In the present work we analyzed the effects
      of amino acid deprivation on intracellular levels of reactive oxygen species
      (ROS) of hepatic stellate cells (HSC), a key cell type in the development of
      liver fibrosis. Histidine deprivation caused in the human immortalized HSC cell
      line LX-2 a fast decrease of intracellular ROS levels that was also observed in
      HSC incubated either with leucine-free or amino acid-free medium, but not with
      glucose-free medium. Phosphorylation of GCN2 kinase and its substrate eIF2alpha
      was induced by histidine deprivation. Reversion studies and activation of GCN2 by
      tRNA and the proteasome inhibitor MG-132 showed a correlation between GCN2
      phosphorylation and diminished ROS levels. However, a lack of correlation between
      eIF2alpha phosphorylation and ROS levels was found using salubrinal, an inhibitor
      of eIF2alpha phosphorylation, suggesting a role for GCN2 unrelated to its
      activity as eIF2alpha kinase. LX-2 cells treated with histidine-free medium
      presented reduced SOD activity that could account for the decrease on ROS levels.
      Histidine deprivation as well as activation of GCN2 by treatment with tRNA,
      caused an increase in LX-2 cell viability, suggesting amino acid restriction to
      present a protective effect in HSC which is mediated by GCN2 activation.

PMID- 20798513
TI  - Long-term high-fat-diet feeding impairs mitochondrial biogenesis in liver of male
      and female rats.
AB  - BACKGROUND/AIMS: Mitochondrial biogenesis includes both mitochondrial
      proliferation and differentiation and its regulation under different
      physiological conditions is not clear. Given the sexual dimorphism previously
      found in mitochondrial function, the aim of this study was to investigate the
      gender-dependent effect of chronic high-fat-diet (HFD) feeding on rat liver
      mitochondrial function and biogenesis. METHODS: Ten-week old male and female rats
      were fed a HFD (26% fat) or a control diet (2.9% fat) for 26 weeks. Mitochondrial
      morphology was studied. Mitochondrial DNA and protein content, hydrogen peroxide
      production, oxidative capacity, antioxidant defenses, as well as markers of
      oxidative damage and mitochondrial biogenesis were analyzed. RESULTS: Female rats
      showed higher levels of mitochondrial protein and an enhanced oxidative capacity
      per mitochondrion than males. In both genders, HFD feeding increased mtDNA
      content and decreased mitochondrial differentiation markers. CONCLUSION: In
      comparison to male rats, females show higher oxidative capacity as a consequence
      of their greater mitochondrial differentiation under both control and obese
      status. In response to HFD feeding, the oxidative capacity of the whole
      mitochondrial population is maintained in both genders. This is obtained by means
      of an enhancement of mitochondrial proliferation, which counteracts the diet
      induced impairment of the function of each mitochondrion.

PMID- 20798514
TI  - RRM2 computational phosphoprotein network construction and analysis between no
      tumor hepatitis/cirrhotic liver tissues and human hepatocellular carcinoma (HCC).
AB  - RRM2 computational phosphoprotein network construction and analysis of human
      hepatocellular carcinoma (HCC) is very useful to identify novel markers and
      potential targets for prognosis and therapy. By integration of gene regulatory
      network infer (GRNInfer) and the database for annotation, visualization and
      integrated discovery (DAVID) we identified and constructed significant molecule
      RRM2 phosphoprotein network from 25 no-tumor hepatitis/cirrhotic liver tissues
      and 25 HCC patients in the same GEO Dataset GSE10140-10141. We gained the
      negative result of RRM2 phosphoprotein module through the net numbers of
      activation minus inhibition compared with no-tumor hepatitis/cirrhotic liver
      tissues and predicted possibly the decrease of RRM2 phosphoprotein module in HCC.
      Our integrative result showed that RRM2 phosphoprotein cluster of HCC contained
      both in human no-tumor hepatitis/cirrhotic liver tissues and HCC terms of
      phosphoprotein (with RRM2) and cell cycle (without RRM2), only in HCC terms of
      cell-cell signaling, cell projection part, glycoprotein, cell projection, cell
      adhesion, biological adhesion, integral to plasma membrane, plasma membrane,
      kinase and phosphorus metabolic process (without RRM2), and none in HCC terms of
      cell death (without RRM2) and ion binding (with RRM2) compared with human no
      tumor hepatitis/cirrhotic liver tissues, all the condition is vital to invasion
      of HCC. Therefore, we deduced the weaker RRM2 phosphoprotein function in HCC
      consistent with our above computation. It would be necessary of RRM2
      phosphoprotein function decrease to invasion of HCC. RRM2 phosphoprotein
      interaction module construction in HCC can be a new route for studying the
      pathogenesis of HCC.

PMID- 20798515
TI  - Uromodulin facilitates neutrophil migration across renal epithelial monolayers.
AB  - The glycosylated protein uromodulin is exclusively found in the thick ascending
      limb cells (TAL) of the kidney, where it is produced on mass and apically
      targeted, eventually being secreted into the urine. Recently, there has been a
      renewed interest in this protein due to its ability to interact with the immune
      system, implicating this protein as a renal inflammatory molecule. Here we
      investigated the potential role of membrane bound uromodulin on neutrophil
      adhesion and trans-epithelial migration. The renal tubular epithelial cell line,
      LLC-PK1, stably transfected with human uromodulin was used to investigate the
      influence of uromodulin on neutrophil adherence and migration. Uromodulin
      expression resulted in a significant increase of neutrophil adherence and trans
      epithelial migration, in both the apical to basolateral and the basolateral to
      apical direction. Although uromodulin is GPI anchored and targeted to the apical
      membrane, we could also observe expression in the basal and lateral membranes
      domains, which may be responsible for basolateral to apical migration.
      Furthermore we show that uromodulin binds both the heavy and light chain of IgG,
      and that IgG enhances neutrophil migration. This study demonstrates that
      uromodulin can facilitate neutrophil trans-epithelial migration and that this
      migration can be amplified by co-factors such as IgG.

PMID- 20798516
TI  - Leukotrienes produced in allergic lung inflammation activate alveolar
      macrophages.
AB  - It has been well-documented that leukotrienes (LTs) are released in allergic lung
      inflammation and that they participate in the physiopathology of asthma. A role
      for LTs in innate immunity has recently emerged: Cys-LTs were shown to enhance
      FcgammaR-mediated phagocytosis by alveolar macrophages (AMs). Thus, using a rat
      model of asthma, we evaluated FcgammaR-mediated phagocytosis and killing of
      Klebsiella pneumoniae by AMs. The effect of treatment with a cys-LT antagonist
      (montelukast) on macrophage function was also investigated. Male Wistar rats were
      immunized twice with OVA/alumen intraperitoneally and challenged with OVA
      aerosol. After 24 h, the animals were killed, and the AMs were obtained by
      bronchoalveolar lavage. Macrophages were cultured with IgG-opsonized red blood
      cells (50:1) or IgG-opsonized K. pneumoniae (30:1), and phagocytosis or killing
      was evaluated. Leukotriene C(4) and nitric oxide were quantified by the EIA and
      Griess methods, respectively. The results showed that AMs from sensitized and
      challenged rats presented a markedly increased phagocytic capacity via FcgammaR
      (10X compared to controls) and enhanced killing of K. pneumoniae (4X higher than
      controls). The increased phagocytosis was inhibited 15X and killing 3X by
      treatment of the rats with montelukast, as compared to the non-treated group. cys
      LT addition increased phagocytosis in control AMs but had no effect on
      macrophages from allergic lungs. Montelukast reduced nitric oxide (39%) and
      LTC(4) (73%). These results suggest that LTs produced during allergic lung
      inflammation potentiate the capacity of AMs to phagocytose and kill K. pneumonia
      via FcgammaR.

PMID- 20798517
TI  - TNF increases expression of IL-4 and PARs in mast cells.
AB  - Tumor necrosis factor (TNF) is a proinflammatory cytokine which has been shown to
      be actively involved in the pathogenesis of allergic inflammation. However,
      little is known of the effects of TNF on cytokine secretion and protease
      activated receptor (PAR) expression in mast cells. In the present study, we
      examined potential influence of TNF on IL-4 and IL-12 release from P815 cells and
      PAR expression in P815 cells by using flow cytometry analysis, quantitative real
      time PCR, ELISA and cellular activation of signaling ELISA (CASE) techniques. The
      results showed that TNF induced up to 2.7-fold increase in IL-4, but not IL-12
      release from P815 cells, and PAR-2 antagonist peptide FSLLRY-NH(2) and PAR-4
      antagonist peptide trans-cinnamoyl (tc)-YPGKF-NH(2) did not affect TNF induced IL
      4 release. Approximately up to 2.4 and 2.3 fold increases in expression of PAR-2
      and PAR-4 were observed when cells were incubated with TNF. Pretreatment of cells
      with TNF for 60 min enhanced trypsin and tryptase induced PAR-2 expression by 2.4
      and 2.3 fold; PAR-3 expression by 1.6 and 1.7 fold and PAR-4 expression by 1.6
      and 1.7 fold, respectively. LY294002, an inhibitor PI3K abolished TNF induced IL
      4 release and phosphorylation of Akt in P815 cells, indicating Akt cell
      signalling pathway is involved in the event. In conclusion, TNF can stimulate IL
      4 release from mast cells through an Akt cell signalling pathway dependent, but
      PAR independent mechanism. TNF may serve as a regulator for IL-4 production and
      PAR expression, and through which participates in the mast cell related
      inflammation.

PMID- 20798518
TI  - Upregulation of Toll-like Receptor (TLR) expression and release of cytokines from
      mast cells by IL-12.
AB  - BACKGROUND: It has been reported that peptidoglycan (PGN) and lipopolysaccharide
      (LPS) can provoke mast cells to release an array of cytokines via TLR2 and TLR4,
      respectively. However, little is known of the regulatory mechanism of TLR2 and
      TLR4 mediated cytokine production in mast cells. METHODS: Since IL-12 plays
      important roles in protection of the body from microorganism infection and mast
      cell is a crucial source of IL-12, we investigated effects of IL-12 on expression
      of TLR2 and TLR4, and cytokine production in mast cells by using quantitative
      real time PCR, flow cytometry analysis and cellular activation of signaling ELISA
      techniques. RESULTS: The results showed that IL-12 induced significant increase
      in expression of TLR2 and TLR4 mRNAs and proteins, respectively. It can also
      synergistically enhance LPS-induced TLR4 expression in P815 cells. IL-12 not only
      by itself, but also synergistically enhanced LPS-induced IL-13 release from P815
      cells. It appears that IL-12 induced IL-13 release and TLR4 expression is through
      activation of MAPK and PI3K/Akt signaling pathways, whereas IL-12 induced
      upregulation of TLR2 is via activation of PI3K/Akt signaling pathway, but not
      MAPK pathway. CONCLUSION: The ability of IL-12 in modulation of expression of
      TLR2 and TLR4 in mast cells, and in stimulation of IL-13 release from mast cells
      provides further evidence that this cytokine may play a role in the protective
      immunity against bacteria infection.

PMID- 20798519
TI  - Effect of amphotericin B on parasitemia and survival of plasmodium berghei
      infected mice.
AB  - Premature death of Plasmodium-infected erythrocytes is considered to favourably
      influence the clinical course of malaria. Amphotericin B has previously been
      shown to trigger suicidal erythrocyte death or eryptosis, which is characterized
      by cell membrane scrambling leading to phosphatidylserine exposure at the cell
      surface. Phosphatidylserine-exposing cells are rapidly cleared from circulating
      blood. The present study thus tested whether amphotericin B exerts a direct
      effect on Plasmodium falciparum and influences eryptosis of infected
      erythrocytes, parasitemia and host survival in murine malaria. To this end, human
      erythrocytes were infected in vitro with Plasmodium falciparum and mice were
      infected with Plasmodium berghei ANKA by in vivo intraperitoneal injection of
      parasitized murine erythrocytes (1x10(6)). Half of the infected mice received
      amphotericin B (1.5 mg/kg b.w. i.v.) from the 8(th) day of infection.
      Amphotericin B (> or = 1 microM) compromised the intracellular development of the
      parasite in human erythrocytes as evident from in vitro growth and DNA
      amplification assays. Amphotericin B further augmented the eryptosis of infected
      human erythrocytes. The administration of amphotericin B to infected mice tended
      to delay the increase of parasitemia and significantly delayed host death. All
      nontreated mice died from malaria within 27 days. In contrast, some 50% of
      amphotericin B-treated mice survived for more than 27 days after infection. In
      conclusion, amphotericin B augmented the suicidal death of infected erythrocytes
      and delayed the lethal course of malaria in Plasmodium berghei infected mice.

PMID- 20798520
TI  - Effect of anandamide in Plasmodium Berghei-infected mice.
AB  - Eryptosis, the suicidal death of erythrocytes, is characterized by exposure of
      phosphatidylserine at the erythrocyte surface and cell shrinkage. Triggers of
      eryptosis include anandamide. Enhanced eryptosis of infected human erythrocytes
      is expected to delay the development of parasitaemia during infection with
      Plasmodium, the parasite causing malaria. The present experiments aimed to test,
      whether anandamide influences eryptosis, parasite growth and/or host survival
      during in vitro or in vivo infection with Plasmodia. Human erythrocytes were
      infected in vitro with P. falciparum, and mice in vivo with P. berghei.
      Parasitemia was determined with Syto16. Phosphatidylserine-exposing erythrocytes
      were identified by analysing annexin V-binding in FACS analysis. In vitro
      infection of human erythrocytes was followed by a significant increase in annexin
      V-binding, an effect slightly enhanced by anandamide (> or = 50 microM), which
      significantly reduced intraerythrocytic DNA/RNA content and in vitro
      parasitaemia. In vivo administration of anandamide (5 mg/kg b.w. subcutaneously)
      blunted the parasitaemia (from 36.9% to 24.2% of circulating erythrocytes 21 days
      after infection) and significantly enhanced the survival of P. berghei-infected
      mice (from 0% to 67% 26 days after infection). The percentage of
      phosphatidylserine-exposing erythrocytes was significantly increased in
      anandamide-treated infected mice compared to non-treated infected mice. In
      conclusion, anandamide stimulated eryptosis of infected erythrocytes thus
      counteracting parasitaemia and a lethal course of the disease.

PMID- 20798522
TI  - Expression analysis of human salivary glands by laser microdissection:
      differences between submandibular and labial glands.
AB  - Both the major and minor salivary glands are the sources of saliva, a fluid vital
      for the maintenance of a healthy oral cavity. Here, the expression profiles of
      human submandibular (SMG) and labial glands (LG) were compared by RT-PCR analysis
      of laser microdissected mucous and serous cells, respectively. The focus was on
      trefoil factor family (TFF) genes, but also other genes encoding secretory
      proteins (mucins, lysozyme, amylase, statherin, and histatins) or aquaporin 5
      were included. Immunofluorescence studies concerning TFF1-3, FCGBP, amylase, and
      lysozyme are also presented. It was shown that LGs clearly contain serous cells
      and that these cells differ in their expression profiles from serous SMG cells.
      Furthermore, all three TFF peptides, together with MUC5B, MUC7, MUC19, and FCGBP,
      were clearly detectable in mucous acini of both LGs and SMGs. In contrast,
      lysozyme was differentially expressed in LGs and SMGs. It can be expected that
      labial saliva may play a particularly important role for protecting the teeth.

PMID- 20798521
TI  - Calcium sensing receptor mutations implicated in pancreatitis and idiopathic
      epilepsy syndrome disrupt an arginine-rich retention motif.
AB  - Calcium sensing receptor (CaSR) mutations implicated in familial hypocalciuric
      hypercalcemia, pancreatitis and idiopathic epilepsy syndrome map to an extended
      arginine-rich region in the proximal carboxyl terminus. Arginine-rich motifs
      mediate endoplasmic reticulum retention and/or retrieval of multisubunit proteins
      so we asked whether these mutations, R886P, R896H or R898Q, altered CaSR
      targeting to the plasma membrane. Targeting was enhanced by all three mutations,
      and Ca(2+)-stimulated ERK1/2 phosphorylation was increased for R896H and R898Q.
      To define the role of the extended arginine-rich region in CaSR trafficking, we
      independently determined the contributions of R890/R891 and/or R896/K897/R898
      motifs by mutation to alanine. Disruption of the motif(s) significantly increased
      surface expression and function relative to wt CaSR. The arginine-rich region is
      flanked by phosphorylation sites at S892 (protein kinase C) and S899 (protein
      kinase A). The phosphorylation state of S899 regulated recognition of the
      arginine-rich region; S899D showed increased surface localization. CaSR assembles
      in the endoplasmic reticulum as a covalent disulfide-linked dimer and we
      determined whether retention requires the presence of arginine-rich regions in
      both subunits. A single arginine-rich region within the dimer was sufficient to
      confer intracellular retention comparable to wt CaSR. We have identified an
      extended arginine-rich region in the proximal carboxyl terminus of CaSR (residues
      R890 - R898) which fosters intracellular retention of CaSR and is regulated by
      phosphorylation. Mutation(s) identified in chronic pancreatitis and idiopathic
      epilepsy syndrome therefore increase plasma membrane targeting of CaSR, likely
      contributing to the altered Ca(2+) signaling characteristic of these diseases.

PMID- 20798523
TI  - Adrenomedullin gene delivery is cardio-protective in a model of chronic nitric
      oxide deficiency combining pressure overload, oxidative stress and cardiomyocyte
      hypertrophy.
AB  - BACKGROUND/AIMS: Chronic inhibition of nitric oxide (NO) synthesis is associated
      with hypertension, myocardial ischemia, oxidative stress and hypertrophy;
      expression of the vasodilator peptide, adrenomedullin (AM) and its receptors is
      augmented in cardiomyocytes, indicating that the myocardial AM system may be
      activated in response to pressure loading and ischemic insult to serve a counter
      regulatory, cardio-protective role. The study examined the hypothesis that
      oxidative stress and hypertrophic remodeling in NO-deficient cardiomyocytes are
      attenuated by adenoviral vector-mediated delivery of the human adrenomedullin
      (hAM) gene in vivo. METHODS: The NO synthesis inhibitor, N(G)-nitro-L-arginine
      methyl ester (L-NAME, 15mg . kg(-1) . day(-1)) was given to rats for 4 weeks
      following systemic administration via the tail vein of a single injection of
      either adenovirus harbouring hAM cDNA under the control of the cytomegalovirus
      promoter-enhancer (Ad.CMV-hAM-4F2), or for comparison, adenovirus alone (Ad.Null)
      or saline. Cardiomyocytes were subsequently isolated for assessment of the
      influence of each intervention on parameters of oxidative stress and hypertrophic
      remodelling. RESULTS: Cardiomyocyte expression of the transgene persisted for >
      or =4 weeks following systemic administration of adenoviral vector. In L-NAME
      treated rats, relative to Ad.Null or saline administration, Ad.CMV-hAM-4F2 (i)
      reduced augmented cardiomyocyte membrane protein oxidation and mRNA expression of
      pro-oxidant (p22phox) and anti-oxidant (SOD-3, GPx) genes; (ii) attenuated
      increased cardiomyocyte width and mRNA expression of hypertrophic (sk-alpha
      actin) and cardio-endocrine (ANP) genes; (iii) did not attenuate hypertension.
      CONCLUSIONS: Adenoviral vector mediated delivery of hAM resulted in attenuation
      of myocardial oxidative stress and hypertrophic remodelling in the absence of
      blood pressure reduction in this model of chronic NO-deficiency. These findings
      are consistent with a direct cardio-protective action in the myocardium of
      locally-derived hAM which is not dependant on NO generation.

PMID- 20798524
TI  - Ventricular remodeling induced by tissue vitamin A deficiency in rats.
AB  - BACKGROUND/AIMS: Experimental studies suggest that vitamin A plays a role in
      regulating cardiac structure and function. We tested the hypothesis that cardiac
      vitamin A deficiency is associated with adverse myocardial remodeling in young
      adult rats. METHODS: Two groups of young female rats, control (C - n = 29) and
      tissue vitamin A deficient (RVA - n = 31), were subjected to transthoracic
      echocardiography exam, isolated rat heart study and biochemical study. RESULTS:
      The RVA rats showed a reduced total vitamin A concentration in both the liver and
      heart [vitamin A in heart, micromol/kg (C = 0.95 +/- 0.44 and RVA = 0.24 +/-
      0.16, p = 0.01)] with the same serum retinol levels (C = 0.73 +/- 0.29 micromol/L
      e RVA = 0.62 +/- 0.17 micromol/L, p = 0.34). The RVA rats showed higher left
      ventricular diameters and reduced systolic function. The RVA rats also
      demonstrated increased lipid hydroperoxide/total antioxidant capacity ratio and
      cardiac levels of IFN-gamma and TNF-alpha but not of metalloproteinase (MMP)-2
      and -9 activity. On the other hand, the RVA rats had decreased levels of beta
      hydroxyacylcoenzyme A dehydrogenase and lactate dehydrogenase. CONCLUSIONS:
      Tissue vitamin A deficiency stimulated cardiac remodeling and ventricular
      dysfunction. Additionally, the data support the involvement of oxidative stress,
      energy metabolism, and cytokine production in this remodeling process.

PMID- 20798525
TI  - Epigallocatechin-3 gallate, a green tea catechin, attenuated the downregulation
      of the cardiac gap junction induced by high glucose in neonatal rat
      cardiomyocytes.
AB  - AIMS: The remodeling of cardiac gap junctions has been postulated to contribute
      to the arrhythmias in a diabetic heart. Epigallocatechin-3 gallate (EGCG), a
      green tea catechin, has recently been recognized for its protection in
      cardiovascular disease. This study investigated the effect of EGCG on the
      possible remodeling of gap junctions under high glucose in cultured neonatal rat
      cardiomyocytes. METHODS: Cardiomyocytes pre-incubated with high glucose (30mM)
      were co-treated by EGCG. The expression of Connexin43 (Cx43), Cx40 and Cx45 were
      determined by Western blot and real-time RT-PCR. The function of cells coupling
      was evaluated by scrape loading dye transfer study. The Mitogen-activated protein
      kinases (MAPK) were quantified by Western blot. RESULTS: The protein expression
      of Cx43 was reduced by high glucose (30mM, 72h). Addition of EGCG to high glucose
      treated cardiomyocytes attenuated the Cx43 reduction in a dose- and time
      dependent manner and also recovered the reduced function of cells coupling. The
      mRNA or protein level of Cx40 and Cx45 showed no significant change by high
      glucose (30mM, 72h) or EGCG co-treatment (40microM, 24h). Nor did the Cx43 mRNA
      level. EGCG (40muM) activated the time-dependent phosphorylated Erk, JNK and p38
      MAPK. The p38 MAPK inhibitor SB203580 (10microM), however, attenuated the
      protective effect of EGCG. CONCLUSION: EGCG could attenuate the downregulation of
      gap junction induced by high glucose in cultured neonatal rat cardiomyocytes. The
      p38 MAPK pathway was partly involved in this effect of EGCG.

PMID- 20798526
TI  - Functional characterization of inward rectifier potassium ion channel in murine
      fetal ventricular cardiomyocytes.
AB  - AIMS: Previous studies have shown the dramatic changes in electrical properties
      of murine fetal cardiomyocytes, while details on inward rectifier potassium
      current (IK1) are still seldom discussed. Thus we aimed to characterize the
      functional expression and functional role of IK1 in murine fetal ventricular
      cardiomyocytes. METHODS: Whole cell patch clamp was applied to investigate the
      electrophysiological properties of IK1. Quantitative real-time PCR, western
      blotting and double-label immunofluorescence were further utilized to find out
      the molecular basis of IK1. RESULTS: Compared to early developmental stage (EDS),
      IK1 at late developmental stage (LDS) displayed higher current density, stronger
      rectifier property and faster activation kinetics. It was paralleled with the
      downregulation of Kir2.3 and the upregulation of Kir2.1/Kir2.2. IK1 contributed
      to maintain the maximum diastolic potential (MDP), late repolarization phase
      (LRP) as well as the action potential duration (APD). However, the contribution
      to MDP and velocity of LRP did not change significantly with maturation.
      CONCLUSIONS: During fetal development, the switch of IK1 subtypes from
      Kir2.1/Kir2.3 to Kir2.1 resulted in the dramatic changes in IK1
      electrophysiological properties.

PMID- 20798527
TI  - Cerebral ischemia elicits aberration in myocardium contractile function and
      intracellular calcium handling.
AB  - The mechanisms of myocardial dysfunction and calcium handling disturbance
      underlying cerebral ischemia remain obscure. Here we for the first time report
      that acute cerebral ischemia significantly increased left ventricular end
      diastolic pressure (LVEDP), but decreased +dP/dt, -dP/dt, and left ventricular
      systolic pressure (LVSP). Significant increase in either the resting or KCl
      induced [Ca2+](i)in ventricular myocytes was also detected by scanning confocal
      microscopy at 2 and 24 hours after cerebral ischemia. Verapamil as a blocker of
      I(Ca,L), ryanodine as a specific inhibitor of RyR, thapsigargin as a highly
      specific inhibitor of sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a (SERCA2a) and
      SEA0400 as a selective NCX inhibitor changed the area under the curve of averaged
      ratio of fluorescence (FI/F(0)I) induced by KCl. Cardiac expression of Ca(v)1.2
      was significantly up-regulated at 2 and 24 hours after cerebral ischemia, whereas
      cardiac expression of SERCA2a and Na(+)-Ca(2+) exchanger (NCX) was significantly
      down-regulated at the same time period after cerebral ischemia. Cardiac
      expression of phospholamban (PLB) was significantly elevated at 2 hours after
      cerebral ischemia but was restored to about normal level at 24 hours after
      injury. These data suggest that acute cerebral ischemia may specifically disturb
      cardiac function and calcium homeostasis, which are related to increase of
      Ca(v)1.2 and decrease of through up-regulating Ca(v)1.2 and PLB, down-regulating
      SERCA2a and NCX, subsequently leading to Ca2+ overload by the enhancement of Ca2+
      influx and inhibition of intracellular Ca2+ extrusion and cerebral ischemia
      induced myocardial dysfunction.

PMID- 20798528
TI  - Genistein suppression of TNF-alpha-induced fractalkine expression in endothelial
      cells.
AB  - Genistein is a polyphenolic nonsteroidal isoflavonoid with estrogen-like activity
      has been shown to have anticancer, antioxidant, and anti-inflammatory activities.
      Fractalkine is a unique chemokine that functions as a chemoattractant and an
      adhesion molecule on endothelial cells activated by proinflammatory cytokines. In
      this study, we investigated the effects of genistein (5-25 muM) on fractalkine
      expression in human umbilical vein endothelial cells (HUVECs) and on its
      receptor, CX3CR1, in THP-1 cells in response to treatment with tumor necrosis
      factor (TNF)- alpha. TNF-alpha significantly induced fractalkine expression in
      endothelial cells. Genistein decreased TNF-alpha-induced fractalkine expression
      through suppression of Akt and p38 phosphorylation and NF-kappaB activities.
      Genistein also strongly suppressed TNF-alpha-induced expression of CX3CR1 in
      monocytes. Genistein suppressed TNF-alpha-stimulated adhesion of monocytes to
      HUVECs. Immunohistochemical analysis revealed that genistein suppressed the in
      vivo lipopolysaccharide (LPS)-induced arterial endothelial fractalkine expression
      in the heart, kidney, and small intestine. These results suggest that genistein
      may provide a new pharmacological approach for suppressing fractalkine/CX3CR1
      mediated injury under vascular inflammatory conditions.

PMID- 20798529
TI  - Lentivirus-mediated RNAi targeting CREB binding protein attenuates neointimal
      formation and promotes re-endothelialization in balloon injured rat carotid
      artery.
AB  - BACKGROUND/AIMS: Lentiviral vectors provide a promising strategy for the
      treatment of cardiovascular diseases, owing to their ability to govern efficient
      and durable gene transfer. However, relatively few studies have been addressed on
      restenosis after balloon or stent associated arterial injury. We previously found
      that CREB binding protein (CBP), a powerful transcriptional coactivator,
      regulated cell proliferation and apoptosis in vascular endothelial and smooth
      muscle cells. Therefore, we investigated whether inhibition of CBP by lentivirus
      mediated small interfering RNA can reduce neointimal formation after arterial
      injury. METHODS: The carotid arteries from Sprague-Dawley rats were injured by
      balloon catheter, followed by incubating with 100 microl lentivirus expressing
      CBP or negative control (NC)-specific short hairpin RNAs (shRNAs) or PBS solution
      for 30 minutes. The rats were euthanized for real-time PCR, Western blot,
      immunohistochemical staining, and morphometric analysis at 4 weeks after balloon
      injury and in vivo gene transfer. RESULTS: Lentiviral shRNA targeting CBP
      markedly reduced CBP expression. Moreover, CBP siRNA showed potent inhibition on
      balloon injury-induced Nuclear factor kappaB (NF-kappaB) acetylation. Compared
      with controls, the significant decrease of neointimal formation by CBP siRNA was
      accompanied by reduced cell proliferation in the neointima of injured arteries.
      However, no changes in medial area were observed among these different groups.
      Interestingly, endothelial cell marker CD31 immunostaining and morphometric
      analysis both showed that CBP knockdown significantly accelerated re
      endothelialization. CONCLUSIONS: These findings suggest that CBP is involved in
      the control of neointimal formation and re-endothelialization via regulating NF
      kappaB acetylation. Lentivirus-mediated CBP silencing may represent a novel
      therapeutic approach for the prevention of restenosis after vascular
      interventions.

PMID- 20798530
TI  - Hyperhomocysteinemia is associated with decreased erythropoietin expression in
      rats.
AB  - BACKGROUND/AIMS: Elevated plasma homocysteine (Hcy) levels have been identified
      as a pathogenic factor causing a variety of pathological changes in different
      cells and tissues. In vertebrates, Hcy is produced solely from S
      adenosylhomocysteine (AdoHcy) through the catalysis of AdoHcy-hydrolase. The
      direction of AdoHcy-hydrolase activity is determined by its cytosolic substrate
      concentrations, thereby controlling intracellular AdoHcy levels. Most S
      adenosylmethionine (AdoMet)-dependent methyltransferases are regulated in vivo by
      the ratio of AdoMet/AdoHcy, which is termed "methylation potential" (MP). To test
      whether high rates of erythropoietin (EPO) expression is reduced by a low MP in
      vivo we choosed the model of increased EPO production following carbon monoxide
      (CO) exposure in rats in which high transcriptional activity is responsible for
      renal EPO production. RESULTS: To induce a sustained hyperhomocysteinemia in
      rats, we infused i.v. a low or high dose of Hcy resulting in Hcy plasma levels of
      87.4+/-6.2 and 300.8+/-23.7 mumol/l, respectively. Renal tissue contents of
      AdoHcy, AdoMet, and adenosine (Ado) were measured after freeze clamp by means of
      HPLC. Within 4h of CO exposure EPO serum levels increased from 13.6+/-0.4
      (control) to 2254.8+/-278.3 mIU/ml. Only high dose of Hcy reduces both, the MP
      from 40.8+/-2.0 to 8.2+/-1.0 in the kidney as well as EPO serum levels by 40%
      compared to control rats. CONCLUSION: Our data show that severe
      hyperhomocysteinemia (HHcy) affects the MP in the renal tissue and lowers EPO
      expression following CO induced intoxication. This result supports the concept
      that efficient EPO production requires an unimpaired MP.

PMID- 20798532
TI  - Reference profile correlation reveals estrogen-like trancriptional activity of
      Curcumin.
AB  - BACKGROUND: Several secondary metabolites from herbal nutrient products act as
      weak estrogens (phytoestrogens), competing with endogenous estrogen for binding
      to the estrogen receptors and inhibiting steroid converting enzymes. However, it
      is still unclear whether these compounds elicit estrogen dependent transcription
      of genes at physiological concentrations. METHODS: We compare the effects of
      physiological concentrations (100 nM) of the two phytoestrogens Enterolactone and
      Quercetin and the suspected phytoestrogen Curcumin on gene expression in the
      breast cancer cell line MCF7 with the effects elicited by 17-beta-estradiol (E2).
      RESULTS: All three phytocompounds have weak effects on gene transcription; most
      of the E2 genes respond to the phytoestrogens in the same direction though to a
      much lesser extent and in the order Curcumin > Quercetin > Enterolactone. Gene
      regulation induced by these compounds was low for genes strongly induced by E2
      and similar to the latter for genes only weakly regulated by the classic
      estrogen. Of interest with regard to the treatment of menopausal symptoms, the
      survival factor Birc5/survivin and the oncogene MYBL1 are strongly induced by E2
      but only marginally by phytoestrogens. CONCLUSION: This approach demonstrates
      estrogenic effects of putative phytoestrogens at physiological concentrations and
      shows, for the first time, estrogenic effects of Curcumin.

PMID- 20798531
TI  - Gender-specific reduction in contraction is associated with increased estrogen
      receptor expression in single vascular smooth muscle cells of female rat.
AB  - Gender differences in the incidence of cardiovascular disease have been related
      to plasma estrogen levels; however, the role of vascular estrogen receptor (ER)
      subtypes in these sex differences is less clear. We tested whether the gender
      differences in vascular smooth muscle (VSM) function reflect differential
      expression/activity of ERalpha, ERbeta and the newly-identified GPR30. Single
      aortic VSM cells (VSMCs) were freshly isolated from male and female Sprague
      Dawley rats, and their contraction to phenylephrine (PHE, 10(-5) M), AngII (10(
      7) M) and membrane-depolarization by KCl (51 mM) was measured in the absence or
      presence of 10(-6) M 17beta-estradiol (E2, stimulant of most ERs), PPT (ERalpha
      agonist), DPN (ERbeta agonist), and ICI 182,780 (an ERalpha/ERbeta antagonist
      with GPR30 agonistic properties). The cells were fixed and fluorescently labeled
      with ERalpha, ERbeta or GPR30 antibody, and the subcellular distribution of ERs
      was examined using digital imaging microscopy. The mRNA expression and protein
      amount of aortic ER subtypes was examined using RT-PCR and Western blots. PHE,
      AngII, and KCl caused less contraction in VSMCs of females than males.
      Pretreatment of VSMCs with E2 reduced PHE-, AngII- and KCl-induced contraction in
      both males and females. PPT caused similar inhibition of PHE-, AngII- and KCl
      induced contraction as E2, suggesting a role of ERalpha. DPN mainly inhibited PHE
      and KCl contraction, suggesting an interaction between ERbeta and Ca(2+)
      channels. ICI 182,780 did not reduce aortic VSMC contraction, suggesting little
      role for GPR30. RT-PCR and Western blots revealed greater expression of ERalpha
      and ERbeta in VSMCs of females than males, but similar amounts of GPR30. The
      total immunofluorescence signal for ERalpha and ERbeta was greater in VSMCs of
      females than males, and was largely localized in the nucleus. GPR30 fluorescence
      was similar in VSMCs of males and females, and was mainly in the cytosol. In PPT
      treated cells, nuclear ERalpha signal was enhanced. DPN did not affect the
      distribution of ERbeta, and ICI 182,780 did not significantly increase GPR30 in
      the cell surface. Thus, ER subtypes demonstrate similar responsiveness to
      specific agonists in VSMCs of male and female rats. The reduced contraction in
      VSMCs of females could be due to gender-related increase in the expression of
      ERalpha and ERbeta.

PMID- 20798533
TI  - Differential patterns of local gene regulation in crush lesions of the rat optic
      and sciatic nerve: relevance to posttraumatic regeneration.
AB  - Axon regrowth after nerve injury can occur in the peripheral but fails in the
      central nervous system. Cellular reactions at the lesion site affect axonal
      regrowth. We compared gene regulation in optic nerve (ON) and sciatic nerve (SN)
      crush lesions in adult rats by cDNA array analysis, quantitative RT-PCR and
      immunohistochemistry, focusing on the primary lesion site rather than the
      proximal or distal nerve stump. Four days after injury, identical gene regulation
      in ON and SN lesions was found for 19/1185 genes (15 up, 4 down). In contrast,
      tissue-specific regulations were identified for 48 genes in ON and 50 genes in SN
      crush lesions. Among these, in the ON many genes were downregulated (23 up, 25
      down) whereas upregulation predominated in SN lesions (43 up, 7 down), especially
      for signaling, metabolism, and translation/transcription-related genes. In ON
      lesions aquaporin 4 downregulation corresponded to a transient loss of
      astrocytes. Tissue-type plasminogen activator was upregulated in the lesion and
      distal stump of SN while the urokinase-type plasminogen activator was upregulated
      only in the ON lesion indicating differences in local proteolysis between the
      systems. Typical neuronal genes were regulated at the crush site comprising
      neurotransmitter genes in ON and actin cytoskeleton-related genes in the SN. The
      differential orchestration of local gene regulation has implications for axonal
      regeneration in central nervous system lesions.

PMID- 20798534
TI  - Does pioglitazone directly influence platelet aggregation?

PMID- 20798535
TI  - Effect of pioglitazone on platelet aggregation in a healthy cohort.
AB  - BACKGROUND: Peroxisome proliferator-activated receptor (PPAR) agonists can
      favorably influence atheroma proliferation, lipoprotein metabolism and
      macrovascular complications. Pioglitazone, one of the thiazolidinedione
      compounds, is a PPAR ligand activator and a clinically important PPAR agonist.
      There is controversy in the literature about its potential antiplatelet effects.
      Its direct platelet inhibition is a novel hypothesis tested in animal models and
      in human populations with underlying diabetic and/or cardiovascular diseases. The
      present study was aimed to test the hypothesis of direct platelet aggregation
      inhibition with the use of pioglitazone in a healthy population. METHODS: This
      prospective study was started after obtaining institutional review board
      approval. The platelet aggregation response to adenosine diphosphate,
      epinephrine, collagen and arachidonic acid was measured in healthy subjects
      before and after treatment with pioglitazone. The fasting lipid profile including
      total cholesterol, low-density lipoprotein, very-low-density lipoprotein and high
      density lipoprotein was also measured. RESULTS: Twenty subjects, 12 males and 8
      females, were enrolled with a mean age of 31.5 +/- 7.6 years (range 24-46). Two
      subjects did not complete the study and were excluded. The mean HbA1C was 5.4%
      (range 4.7-5.7). The study showed a non-significant platelet aggregation
      reduction after taking a 7-day pioglitazone course. The adenosine diphosphate
      mediated platelet aggregation difference was not significant (p = 0.99); the
      arachidonic acid-mediated platelet aggregation difference was 0.6% (p = 0.93),
      for epinephrine 0.9% (p = 0.88) and for collagen 0.2% (p = 0.94). Further, it did
      not show a favorable response of lipoprotein profile with a non-significant
      reduction in all lipid panel values even though there is a slight reduction in
      total cholesterol, triglyceride, low-density lipoprotein and very low-density
      lipoprotein and a slight increase in high-density lipoprotein. CONCLUSIONS: We
      conclude that pioglitazone does not have a direct platelet aggregation inhibition
      effect in a healthy population, nor does it have a favorable effect on
      lipoprotein profile after a short treatment period.

PMID- 20798536
TI  - Fast in the aorta, slow in the coronaries.

PMID- 20798537
TI  - Aortic pressures, stiffness and left ventricular function in coronary slow flow
      phenomenon.
AB  - BACKGROUND: Coronary slow flow (CSF) phenomenon is characterized by delayed
      opacification of coronary vessels in a normal coronary angiogram. Although
      clinical and pathological features have been previously described, the underlying
      pathophysiology has not been fully elucidated. In this study, we aimed to
      evaluate central aortic pressure, aortic stiffness and left ventricular (LV)
      function in patients with coronary slow flow. METHOD AND RESULTS: The study
      population consisted of 154 patients who underwent coronary angiography because
      of typical and quasi-typical symptoms of angina. 81 patients with
      angiographically proven CSF and 73 cases with normal coronary flow pattern with
      similar risk profiles were enrolled in the study. Aortic pressures and indexes of
      elastic properties were evaluated using invasive methods. Aortic pulse pressure
      (mm Hg) and pulsality index of patients with CSF were found to be significantly
      higher than those of controls (60.8 +/- 13.8 vs. 53.7 +/- 14.5, p = 0.002; 0.84
      +/- 0.22 vs. 0.67 +/- 0.18, p = 0.0001, respectively). LV Doppler parameters were
      deteriorated in patients with CSF. Aortic fractional pulse pressure and pulsality
      index were significantly correlated with the mean TIMI frame count and LV
      diastolic parameters in correlation analysis. CONCLUSION: The present findings
      allow us to conclude that impaired aortic elasticity in patients with CSF may
      also be responsible for the impaired LV diastolic parameters.

PMID- 20798538
TI  - Obsessive-compulsive behavior as a symptom of dementia in progressive
      supranuclear palsy.
AB  - AIMS: To describe obsessive-compulsive symptoms (OCS) as under-recognized
      behavioral and psychological symptoms of dementia of progressive supranuclear
      palsy (PSP) and to discuss possible mechanisms based on MRI and SPECT findings.
      METHODS: We studied 74 PSP patients. OCS are defined as persistent and
      unreasonable, but non-delusional/hallucinatory, ideas and behaviors. Demography,
      cognition, the widths of middle cerebellar peduncles (MCP) and the inter-caudate
      distances (ICD), both corrected by the intracranial size (MCP and ICD ratios),
      and changes on voxel-based SPECT were compared between the subgroups with and
      without OCS. Finally, the predicative power of various factors to OCS was
      investigated. RESULTS: We observed OCS in 18 patients (24%). They were obsessed
      with daily trifles and physical symptoms among other things. OCS was not
      associated with demography or cognitive levels. OCS-positive patients had
      significantly smaller MCP and ICD ratios and showed marked uptake decreases in
      the orbitofrontal cortex, caudate and thalamus. Relative uptake increases in the
      cerebellum, specifically the tonsils, were milder in OCS-positive than -negative
      patients. A smaller right MCP, a smaller ICD ratio and lower uptake increases in
      the right cerebellar were the significant predictors of OCS. CONCLUSIONS: OCS are
      frequent but under-recognized behavioral and psychological symptoms of dementia
      in PSP. Dysfunction of the fronto-caudate-thalamus-cerebellum circuit may be
      involved.

PMID- 20798539
TI  - Subtle deficits in instrumental activities of daily living in subtypes of mild
      cognitive impairment.
AB  - BACKGROUND/AIMS: Greater cognitive and functional deficits in mild cognitive
      impairment (MCI) are associated with higher rates of dementia. We explored the
      relationship between these factors by comparing instrumental activities of daily
      living (IADLs) among cognitive subtypes of MCI and examining associations between
      IADL and neuropsychological indices. METHODS: We analyzed data from 1,108 MCI and
      3,036 normal control subjects included in the National Alzheimer's Coordinating
      Center Uniform Data Set who were assessed with the Functional Activities
      Questionnaire (FAQ). RESULTS: IADL deficits were greater in amnestic than
      nonamnestic MCI, but within these subgroups, did not differ between those with
      single or multiple domains of cognitive impairment. FAQ indices correlated
      significantly with memory and processing speed/executive function. CONCLUSIONS:
      IADL deficits are present in both amnestic MCI and nonamnestic MCI but are not
      related to the number of impaired cognitive domains. These cross-sectional
      findings support previous longitudinal reports suggesting that cognitive and
      functional impairments in MCI may be independently associated with dementia risk.

PMID- 20798540
TI  - Plasma homocysteine and cognition in elderly patients with dementia or other
      psychogeriatric diseases.
AB  - BACKGROUND: Total plasma homocysteine (tHcy) concentration is elevated in elderly
      patients with mental illness, and patients with vascular disease have higher
      plasma tHcy concentrations than patients without vascular disease. Increasing
      evidence indicates that vascular risk factors play a role in the development of
      cognitive impairment. METHOD: We have investigated the relation between plasma
      tHcy, its determinants and cognition, measured as MMSE, in 448 consecutively
      enrolled patients with dementia or other psychogeriatric diseases. RESULTS:
      Multiple regression analyses showed that plasma tHcy was related to cognitive
      function in all patients as well as in demented and non-demented patients. The
      apparent close relationship between plasma tHcy and cognition was mainly
      dependent on its determinant age, whereas the other determinants of plasma tHcy
      exhibited a limited influence on the relation between plasma tHcy and cognition.
      Plasma tHcy has its own, albeit modest, relationship to cognitive function
      (predictive value about 5%). CONCLUSION: Plasma tHcy itself seems to play a minor
      role in cognitive impairment in patients with dementia or other psychogeriatric
      diseases. When investigating the relation between plasma tHcy and cognition, it
      is important to consider the distribution of the main determinants of plasma tHcy
      and to correct plasma tHcy for these variables.

PMID- 20798541
TI  - Thyroid hormones are associated with poorer cognition in mild cognitive
      impairment.
AB  - BACKGROUND: Alterations in interrelated endocrine axes may be related to the
      pathogenesis of mild cognitive impairment (MCI) and dementia. METHODS: Salivary
      cortisol before and after a 0.5-mg dexamethasone test, and serum levels of
      thyroid-stimulating hormone, total thyroxine (T(4)), free T(4), total
      triiodothyronine (TT(3)), estradiol, testosterone and insulin-like growth factor
      1 were measured in 43 MCI cases and 26 healthy controls. All participants
      underwent a comprehensive neuropsychological test battery covering the cognitive
      domains of speed/attention, memory, visuospatial functions, language and
      executive functions. RESULTS: The MCI group did not differ in basal levels of
      endocrine markers compared to controls. Among those with MCI, TT(3) levels were
      inversely associated with cognitive performance across all domains. After
      stratifying MCI cases according to TT(3) levels, those with relatively high TT(3)
      levels showed impairment in memory as well as in visuospatial and executive
      functions. Those with TT(3) levels at or below the lower boundary of the normal
      range performed comparably to healthy controls. Other endocrine markers were not
      related to cognitive performance. CONCLUSIONS: Among those with MCI, TT(3) was
      associated with a neuropsychological profile typical of prodromal Alzheimer's
      disease. While the mechanisms remain unclear, optimal levels of thyroid hormone
      under a compromising condition such as MCI and related neuropathology need
      reconsideration.

PMID- 20798542
TI  - Is there an association between the use of anabolic-androgenic steroids and
      criminality?
AB  - AIMS: The aim of this study was to improve our understanding of the proposed
      association between anabolic-androgenic steroids (AAS) and criminality. METHODS:
      The study was based on interviews and criminality data involving 32 users of AAS
      who had sought treatment for AAS-related problems at a psychiatric addiction
      clinic in Sweden. A score derived from the number of crimes, their level of
      severity and the relevant time periods was computed to allow comparisons between
      subgroups sorted according to type and timing of drug use. RESULTS: The criminal
      activity level increased for 69% of the individuals after having started to use
      drugs. This was particularly obvious in the group who had started its involvement
      with drugs by using AAS. Crimes of violence and weapon offences showed a great
      increase in incidence after drug use had been initiated. The study also showed a
      significant decrease in criminality after treatment, particularly among
      individuals who had started their drug use with AAS. CONCLUSION: The results
      suggest that there is an association between the use of AAS and criminality,
      especially with regard to crimes of violence and weapon offences, and that this
      criminality may be enhanced when AAS are combined with other drugs of abuse.

PMID- 20798544
TI  - A case report of inpatient detoxification after kratom (Mitragyna speciosa)
      dependence.
AB  - Kratom (Mitragyna speciosa) has been used for medicinal and recreational
      purposes. It has reported analgesic, euphoric and antitussive effects via its
      action as an agonist at opioid receptors. It is illegal in many countries
      including Thailand, Malaysia, Myanmar, South Korea and Australia; however, it
      remains legal or uncontrolled in the UK and USA, where it is easily available
      over the Internet. We describe a case of kratom dependence in a 44-year-old man
      with a history of alcohol dependence and anxiety disorder. He demonstrated
      dependence on kratom with withdrawal symptoms consisting of anxiety,
      restlessness, tremor, sweating and cravings for the substance. A reducing regime
      of dihydrocodeine and lofexidine proved effective in treating subjective and
      objective measures of opioid-like withdrawal phenomena, and withdrawal was
      relatively short and benign. There are only few reports in the literature of
      supervised detoxification and drug treatment for kratom dependence. Our
      observations support the idea that kratom dependence syndrome is due to short
      acting opioid receptor agonist activity, and suggest that dihydrocodeine and
      lofexidine are effective in supporting detoxification.

PMID- 20798543
TI  - Liquid drugs and high dead space syringes may keep HIV and HCV prevalence high -
      a comparison of Hungary and Lithuania.
AB  - Despitevery similar political, drug policy and HIV prevention backgrounds, HIV
      and HCV prevalence is considerably different in Hungary (low HIV and moderate HCV
      prevalence) and Lithuania (high HCV and moderate HIV prevalence). Wecompared the
      drug use profile of Hungarian (n = 215) and Lithuanian (n = 300) injecting drug
      users (IDUs). Overall, compared with IDUs in Hungary, IDUs in Lithuania often
      injected opiates purchased in liquid form ('shirka'), used and shared 2-piece
      syringes (vs. 1-piece syringes) disproportionately more often, were less likely
      to acquire their syringes from legal sources and had significantly more
      experience with injected and less experience with non-injected drugs. It may not
      be liquid drugs per se that contribute to a higher prevalence of HCV and/or HIV,
      but it is probably factors associated with the injecting of liquid drugs, such as
      the wide-spread use and sharing of potentially contaminated 2-piece syringes
      acquired often from non-legal sources, and syringe-mediated drug sharing with 2
      piece syringes. Scaling up substitution therapy, especially heroin replacement,
      combined with reducing the supply of liquid drugs may decrease the prevalence of
      high-risk injecting behaviours related to the injecting of liquid drugs and drug
      injecting-related infections among IDUs in Lithuania.

PMID- 20798545
TI  - Damage to the upper portion of area 19 and the deep white matter in the left
      inferior parietal lobe, including the superior longitudinal fasciculus, results
      in alexia with agraphia.
AB  - Analysis of lesions and symptoms in patients with brain tumors combined with
      information from diffusion tensor imaging provides direct evidence of the
      anatomical localization of brain function. Using these methods, we evaluated 8
      patients who underwent surgery for metastatic brain tumors located in the left
      occipital lobes between 2007 and 2009. Preoperatively, 4 patients (cases 1-4) had
      alexia with agraphia while the other 4 patients (cases 5-8) did not. Tractography
      for the superior longitudinal fasciculus (SLF) was performed before surgery in
      case 1. The common brain tumors in cases 1-4 were located in the upper portion of
      area 19, and peritumor edema in that area resulted in compromise of the deep
      white matter of the inferior parietal lobe (IPL). The SLF was compressed and
      disrupted in the white matter of the IPL near the upper portion of area 19 in
      case 1. In cases 5-8, the brain tumors were not located in the upper portion of
      area 19. These results suggest that damage to the upper portion of area 19 and to
      the white matter in the left IPL, including the SLF, resulted in alexia with
      agraphia.

PMID- 20798546
TI  - Ex vivo pulsatile perfusion of human saphenous veins induces intimal hyperplasia
      and increased levels of the plasminogen activator inhibitor 1.
AB  - Vessel wall trauma induces vascular remodeling processes including the
      development of intimal hyperplasia (IH). To assess the development of IH in human
      veins, we have used an ex vivo vein support system (EVVSS) allowing the perfusion
      of freshly isolated segments of saphenous veins in the presence of a pulsatile
      flow which reproduced arterial conditions regarding shear stress, flow rate and
      pressure during a period of 7 and 14 days. Compared to the corresponding freshly
      harvested human veins, histomorphometric analysis showed a significant increase
      in the intimal thickness which was already maximal after 7 days of perfusion.
      Expression of the endothelial marker CD31 demonstrated the presence of
      endothelium up to 14 days of perfusion. In our EVVSS model, the activity as well
      as the mRNA and protein expression levels of plasminogen activator inhibitor 1,
      the inhibitor of urokinase-type plasminogen activator (uPA) and tissue-type
      plasminogen activator (tPA), were increased after 7 days of perfusion, whereas
      the expression levels of tPA and uPA were not altered. No major change was
      observed between 7 and 14 days of perfusion. These data show that our newly
      developed EVVSS is a valuable setting to study ex vivo remodeling of human veins
      submitted to a pulsatile flow.

PMID- 20798547
TI  - Partial liver ischemia is followed by metabolic changes in the normally perfused
      part of the liver during reperfusion.
AB  - BACKGROUND: Temporary vascular in- and outflow occlusion is an effective
      technique for bleeding control during liver resection. However, occlusion can
      result in ischemia/reperfusion (I/R) injury to the liver. The aim of this study
      in a porcine model was to investigate the effect of in- and outflow occlusion of
      part of the liver on the metabolism of the normally perfused parenchyma of the
      same liver measured by microdialysis. METHODS: Eight pigs underwent laparotomy. A
      microdialysis catheter was inserted into in the left and right part of the liver,
      respectively. Microdialysis samples were collected every 30 min. Occlusion of the
      left part of the liver was achieved for 60 min, followed by 5 h of reperfusion.
      Samples were analyzed for glucose, lactate, pyruvate and glycerol. Blood samples
      were drawn to determine standard liver and biochemical parameters. RESULTS:
      Comparing the ischemic part of the liver with the normally perfused part,
      significant differences in the levels of lactate, pyruvate and glycerol were
      found. During reperfusion, similar and continuous decreases below baseline levels
      were observed for lactate and pyruvate in both the ischemic and normally perfused
      part of the liver. No significant changes in liver parameters or blood glucose
      levels were seen. CONCLUSIONS: Partial ischemia of the liver is without effects
      on metabolism in the normally perfused part. Metabolic changes in the ischemic
      part of the liver were reversible. However, partial liver ischemia was followed
      by similar continuous decreases in lactate and pyruvate levels in the whole
      liver, even though the ischemic insult was not detectable in transaminase levels.

PMID- 20798548
TI  - Reinforcement of colonic anastomoses with a collagenous double-layer matrix
      extracted from porcine dermis.
AB  - BACKGROUND: Anastomotic leakage is a major factor for morbidity in colorectal
      surgery. Anastomotic reinforcement with biological or synthetic materials has
      been claimed to be useful in preventing anastomotic leakage. METHODS: We
      evaluated a non-cross-linked collagenous matrix Bio-Gide (BG) for sealing colonic
      anastomoses in a rodent model. The animals were investigated for 4, 30 and 90
      days. Macroscopic examination, histological examination and measurement of
      bursting pressure were performed. The anastomotic stricture rate was evaluated by
      radiographic contrast enema. RESULTS: Microscopically anastomoses sealed by BG
      showed impaired anastomotic healing. Blood vessel ingrowth and collagen
      deposition were decreased without reaching significance after 4 days. The
      anastomotic bursting pressure was significantly decreased (p = 0.0454) in the
      early phase of healing. Anastomotic neovascularization was significantly
      decreased compared to the control group after 30 (p = 0.0058) and 90 days (p =
      0.0275). Although no difference in anastomotic stricture rate was evident, the
      rate of intra-abdominal adhesions was significantly increased after 30 (p =
      0.0124) and 90 days (p = 0.0281). CONCLUSION: BG failed to improve colonic
      anastomotic healing. Early anastomotic healing was impaired if anastomoses were
      reinforced with BG. BG did not affect the anastomotic stricture rate for up to 3
      months; nevertheless, intra-abdominal adhesions were increased.

PMID- 20798549
TI  - Biotin starvation with adequate glucose provision causes paradoxical changes in
      fuel metabolism gene expression similar in rat (Rattus norvegicus), nematode
      (Caenorhabditis elegans) and yeast (Saccharomyces cerevisiae).
AB  - BACKGROUND/AIM: Biotin affects the genetic expression of several glucose
      metabolism enzymes, besides being a cofactor of carboxylases. To explore how
      extensively biotin affects the expression of carbon metabolism genes, we studied
      the effects of biotin starvation and replenishment in 3 distantly related
      eukaryotes: yeast Saccharomyces cerevisiae, nematode Caenorhabditis elegans and
      rat Rattus norvegicus. METHODS: Biotin starvation was produced in Wistar rats, in
      C. elegans N2 and S. cerevisiae W303A fed with abundant glucose. High-density
      oligonucleotide microarrays were used to find gene expression changes. Glucose
      consumption, lactate and ethanol were measured by conventional tests. RESULTS: In
      spite of abundant glucose provision, the expression of fatty oxidation and
      gluconeogenic genes was augmented, and the transcripts for glucose utilization
      and lipogenesis were diminished in biotin starvation. These results were
      associated with diminished glucose consumption and glycolysis products (lactate
      and ethanol in yeast), which was consistent across 3 very different eukaryotes.
      CONCLUSION: The results point toward a strongly selected role of biotin in the
      control of carbon metabolism, and in adaptations to variable availability of
      carbon, conceivably mediated by signal transduction including soluble guanylate
      cyclase, cGMP and a cGMP-dependent protein kinase (PKG) and/or biotin-dependent
      processes.

PMID- 20798550
TI  - Effect of Sauropus androgynus leaf extracts on the expression of prolactin and
      oxytocin genes in lactating BALB/C mice.
AB  - Sauropus androgynus is traditionally consumed by Indonesians and is believed to
      increase breast milk production during lactation. Lactation, a process of milk
      synthesis and secretion, occurs with the help of 2 hormones, prolactin and
      oxytocin. The expressions of genes encoding prolactin and oxytocin were analyzed
      in lactating BALB/C mice brains using qRT-PCR. A total of 24 lactating BALB/C
      mice were fed with experimental diets for 12 days. Two groups of lactating mice
      were fed with diets containing either young or mature S. androgynus leaf
      extracts. For the control, one group of lactating mice was fed a diet without S.
      androgynus leaf extracts. Supplementation of young S. androgynus leaf extracts
      increased the expression of prolactin and oxytocin genes in lactating mice 9.04-
      and 2.25-fold, respectively. Meanwhile, supplementation of mature S. androgynus
      leaf extracts increased the expressions of both genes 15.75- and 25.77-fold,
      respectively, compared to the control group. The result suggested that mature S.
      androgynus leaf extracts significantly increased the expressions of both genes in
      lactating BALB/C mice and was predicted to correlate with papaverine content,
      which is only detected in mature S. androgynus leaves at a concentration of 0.38
      +/- 0.04 MUg.ml(-1).

PMID- 20798551
TI  - Incidence of epilepsy in a defined area of Central Anatolia, Turkey, after 15
      years of age.
AB  - BACKGROUND: The aim of this study was to establish the incidence rate, incidence
      related characteristics, and epidemiological profile of epilepsy in Eskisehir,
      Turkey. METHODS: Cases were prospectively recorded by utilizing multiple data
      sources, including case records obtained through the Hospital Information System,
      files kept by family physicians, and files kept by private neurologists. Patients
      diagnosed with epilepsy between July 1, 2007, and June 30, 2008, and above the
      age of 15 years were included in the study. RESULTS: 219 new cases were diagnosed
      with epilepsy. The adjusted incidence rate was 33.51/100,000 cases in males and
      42.22/ 100,000 cases in females, for a total of 37.59/100,000 persons. The
      incidence rates according to age were found to be highest in the 15-19-year age
      group and in the >=70-year age group. Partial seizures were observed more than
      generalized seizures after the age of 40. Unknown etiology accounted for 77.2% of
      the epilepsies. Stroke was the most common etiological cause of epilepsy among
      the symptomatic group. CONCLUSIONS: The incidence rate of epilepsy in Eskisehir
      was comparable with the rates reported for developed countries.

PMID- 20798552
TI  - Lipopolysaccharide-induced expression of Th1/Th2 cytokines in whole neonatal cord
      and adult blood: role of nuclear factor-kappa B and p38 MAPK.
AB  - BACKGROUND: Sepsis continues to be a leading cause of morbidity and mortality in
      newborns. OBJECTIVE: As both nuclear factor-kappa B (NF-kappaB) and p38 mitogen
      activated protein kinase (MAPK) appear to be critical mediators in inflammatory
      response, we studied the effects of lipopolysaccharide (LPS) on expression and
      function of NF-kappaB and p38 MAPK in whole neonatal cord and adult blood.
      METHODS: Th1/Th2 cytokine concentrations and phosphorylation of NF-kappaB and p38
      MAPK were determined by flow-cytometric analysis. RESULTS: Tumor necrosis factor
      alpha (TNF-alpha), IL-6, and IL-10 concentrations were significantly elevated in
      supernatants of neonatal and adult blood after LPS stimulation for 4 h. IFN
      gamma, IL-4, and IL-2 showed no significant alterations. Furthermore, TNF-alpha
      concentrations were significantly higher in adult compared to neonatal blood
      after LPS stimulation. Stimulation with LPS resulted in significantly decreased
      activation of p38 MAPK in neonatal blood, whereas NF-kappaB showed no difference.
      Following inhibition of p38 MAPK with the specific inhibitor SB-202190, levels of
      TNF-alpha and IL-6 significantly decreased in neonatal and adult blood, whereas
      pharmacological inhibition of NF-kappaB with SC-514 showed no significant effect
      on cytokine expression. CONCLUSIONS: We conclude that p38 MAPK phosphorylation is
      crucially involved in LPS activation and could explain the differences in early
      cytokine response between neonatal and adult blood.

PMID- 20798554
TI  - History of the ductus arteriosus: 2. Persisting patency in the preterm infant.
AB  - By 1769, it was known to Morgagni that the ductus arteriosus may persist until
      adulthood. In 1835, Jorg linked delayed postnatal closure with disturbed
      respiration, a discovery that was afterwards forgotten for a century. When blood
      gas analysis became available, the association between persisting patency and
      diminished oxygenation resurfaced. When it became known that prostaglandins
      played a role in maintaining ductal patency, the development of pharmacologic
      intervention with cyclooxygenase inhibitors immediately followed. This rapid
      progress was due to the interaction between basic science, pediatric cardiology,
      and neonatology disciplines at the Cardiovascular Research Institute in San
      Francisco, coordinated by Julius Comroe, as well as President Kennedy's
      foundation of the National Institute of Child Health and Development. This series
      of events exemplifies how clinical research became an integrated managed
      multidisciplinary endeavor in the 20th century.

PMID- 20798553
TI  - Is it possible to make a reliable prognosis within the first hour of life for
      very low birth weight infants delivered after preterm premature rupture of
      membranes?
AB  - BACKGROUND: One third of all preterm births are due to preterm premature rupture
      of membranes (pPROM). An accurate prognostic evaluation after admission to the
      neonatal intensive care unit is necessary. OBJECTIVE: The aim of this study was
      to identify prognostic factors within the first hour of life for mortality, short
      term pulmonary morbidity, chronic lung disease (CLD) and severe cerebral
      morbidity in very low birth weight (VLBW) infants after pPROM. METHODS: This
      retrospective study included 300 infants with pPROM who fit the study criteria
      and were derived from a cohort of 1,435 VLBW infants. A total of 17 obstetric and
      neonatal factors were evaluated by univariate and multivariate analysis. RESULTS:
      Gestational age at birth and 5-min Apgar score correlated significantly with all
      4 outcomes. The results of the first blood gas analysis correlated with 3
      outcomes and the first mean arterial pressure with 2 outcomes. Anhydramnios and a
      lower number of courses of antenatal steroids correlated with higher mortality,
      and preterm labor correlated with CLD. The multivariate analysis revealed
      gestational age, 5-min Apgar score, the results of the first blood gas analysis,
      the first mean arterial pressure and anhydramnios to be significant predictors.
      The positive predictive value ranged from 20 to 81%, and the negative predictive
      value ranged from 79 to 92%. CONCLUSION: Gestational age at birth and parameters
      reflecting postnatal adaptation were the most precise factors for assessment of
      the prognosis of VLBW infants after pPROM within the first hour of life. Apart
      from anhydramnios, obstetric factors did not predict neonatal outcome. At 1 h of
      age, our models of perinatal risk factors were more effective in predicting a
      favorable outcome than an adverse outcome.

PMID- 20798555
TI  - A survey of intravenous sodium bicarbonate in neonatal asphyxia among European
      neonatologists: gaps between scientific evidence and clinical practice.
AB  - BACKGROUND: Birth asphyxia is characterized by intermittent periods of
      hypoxia/ischemia leading to metabolic acidosis. The use of intravenous sodium
      bicarbonate (IVSB) is still a matter of controversy in clinical practice.
      OBJECTIVE: To assess the use of IVSB in birth asphyxia by attending
      neonatologists in European hospitals. DESIGN/METHODS: Survey using a
      questionnaire administered to neonatologists in Europe whose electronic addresses
      were provided by the national councils of neonatology of each participating
      country. The questionnaire consisted of a brief theoretical introduction followed
      by demographic questions related to the respondent's professional qualification.
      This was followed by a clinical case of an asphyxiated term neonate with severe
      combined metabolic and respiratory acidosis and case-specific questions related
      to the perceived indication for administration of IVSB and use of additional
      therapies to address the clinical situation. Descriptive statistics and chi2
      analysis were performed. RESULTS: The questionnaire was answered by 259
      neonatologists from 17 countries. IVSB was believed to be indicated by 109
      (42.2%) of the respondents in this clinical scenario. Results differed
      significantly between countries, with IVSB use varying from as high as 68% in
      Portugal and <5% in Scandinavian countries. However, there were no differences in
      the choice of other therapeutic measures. CONCLUSIONS: Although scientific
      evidence suggests that IVSB is not effective in asphyxiated newborns and current
      guidelines do not recommend its use, 42.2% of the consulted neonatologists in
      Europe would use it, with significant differences between but not within
      countries. There were no differences regarding additional measures to overcome
      asphyxia. Strategies to implement use of internationally accepted guidelines are
      needed.

PMID- 20798556
TI  - Computation of Na and water deficit of iso-osmolar dehydration.
AB  - BACKGROUND AND AIMS: The presence of altered plasma Na concentration (PNa) allows
      calculations of changes in water and electrolyte contents, which are not feasible
      during normonatremic derangements. We have developed a computational algorithm
      whereby the changes in solute (DeltaNa and DeltaCl) and solvent (DeltaV) contents
      can be computed exactly when Na is lost entirely as NaCl (or NaHCO(3)) and nearly
      exactly in all other circumstances, except when the losses of Na and Cl occur in
      the same proportions as those of the normal plasma concentration of these ions.
      METHODS: In computer experiments, we simulated different fluid depletions
      containing 140 mEq/l of Na (which is to say, DeltaNa/DeltaV ~ 140), coupled with
      variable ratios in Na to Cl losses (variable DeltaNa/DeltaCl). The data were back
      calculated with our algorithms from the ensuing plasma ion concentrations
      (PNa(1), PCl(1) and POAN(1), where subscript (0) and (1) indicate normal and
      deranged plasma concentration values, respectively, and OAN indicates anions
      other than Cl), as if they had been measured on patients, and from known normal
      values (TBW(0), ECV(0), Na(0)). These were compared to the true values used to
      build the simulations. This procedure was reproduced in 17 patients suffering
      from iso-osmolar dehydration, where true data were obtained by balance studies.
      RESULTS: True and calculated data were compared with linear regression analysis.
      We obtained significant correlations both in computer-simulated and real patients
      (R(2) = 0.83, p < 0.005 and R(2) = 0.63, p < 0.05, respectively). CONCLUSION:
      This new math model and its related computational method are useful in the
      correct evaluation and treatment of iso-osmolar dehydration.

PMID- 20798557
TI  - A multicenter phase II trial with irinotecan plus oxaliplatin as first-line
      treatment for inoperable/metastatic cancer of the biliary tract.
AB  - PURPOSE: To evaluate the efficacy and tolerability of oxaliplatin (L-OHP) in
      combination with irinotecan (CPT-11) as first-line treatment of advanced biliary
      tract cancer. PATIENTS AND METHODS: Patients with histologically confirmed
      nonresectable biliary adenocarcinoma were treated with oxaliplatin (85 mg/m(2))
      and irinotecan (200 mg/m(2)) every 3 weeks. RESULTS: Twenty-eight patients were
      enrolled between May 2005 and March 2009. The overall objective response rate was
      17.9% with an additional 21.4% of patients with stable disease (disease control
      rate 39.3%). The median overall survival time was 9.2 months (95% CI 5.8-12.5)
      and the median progression-free survival time 2.7 months (95% CI 2.2-3.2). Grades
      3 and 4 neutropenia occurred in 1 (3.6%) and 4 (14.3%) patients, respectively,
      and febrile neutropenia in 3 (10.7%). Grade 3-4 diarrhea was observed in 2 (7.1%)
      patients and grade 3 asthenia in 1 (6%). There were no treatment-related deaths.
      CONCLUSION: The combination of oxaliplatin and irinotecan has a modest antitumor
      activity with manageable toxicity as first-line treatment in metastatic cancer of
      the biliary tract and therefore it cannot be recommended as front-line treatment
      for unresectable biliary tract cancer.

PMID- 20798558
TI  - The significance of fibroblast growth factor receptor 2 expression in
      differentiation of hepatocellular carcinoma.
AB  - Fibroblast growth factor receptors (FGFRs) have been reported to be involved in
      the progression of many cancers. The aim of this study is to clarify the
      significance of FGFR2 expression in the differentiation of hepatocellular
      carcinoma (HCC). One nodule-in-nodule HCC sample was obtained from a patient to
      analyze the different expression in well- to moderately differentiated HCC and
      poorly differentiated HCC using microarray technique. The expression of FGFR2 in
      46 patients with surgically resected HCC was immunohistochemically examined and
      analyzed in relation to their clinicopathological factors. Fgfr2 was 4.7 times up
      regulated in poorly differentiated HCC from a nodule-in-nodule sample. The high
      expression group was 16 cases and the low expression group was 30 cases. The high
      FGFR2 expression correlated significantly with a poor histological
      differentiation, a higher incidence of portal vein and a high level of alpha
      fetoprotein. The overall survival rates and the disease-free survival rates in
      high expression were significantly worse than those in low. In conclusion, a high
      FGFR2 expression plays an important role in poor differentiation, portal vein
      invasion, high alpha-fetoprotein production, and poor prognosis. These data
      suggest that FGFR2 may be a potentially useful biological marker of tumor
      invasiveness in HCC as well as a novel molecular target for HCC.

PMID- 20798559
TI  - Predictive factors of complete response to neoadjuvant chemoradiotherapy in
      patients with rectal cancer.
AB  - PURPOSE: Pathological complete response (pCR) after neoadjuvant chemoradiotherapy
      is a favorable prognosticator in rectal cancer patients. We investigated whether
      the biological features of the primary tumor affect pCR. MATERIALS AND METHODS:
      Forty-six patients treated with capecitabine-oxaliplatin and pelvic conformal
      radiotherapy were considered. Forty-three patients underwent surgery, and the
      pathologic response was scored according to the tumor regression grade (TRG)
      scale. Epidermal growth factor receptor (EGFR), vascular endothelial growth
      factor, poly(adenosine diphosphate-ribose) polymerase-1, X-ray cross
      complimenting, thymidylate synthase (TS) and Ki67 expression were evaluated by
      immunohistochemistry on rectal biopsies obtained before chemoradiotherapy, and
      scored as the percentage of positive cells. Cutoffs were selected based on ROC
      analysis. The correlation between the biological factors and the TRG coded as
      TRG1 (pCR) versus TRG >=2 (no pCR) was assessed by the chi(2) test and logistic
      regression analysis. RESULTS: Low EGFR (p = 0.007), high TS (p = 0.002), and high
      Ki67 (p = 0.05) were strongly associated with pCR. Upon univariate analysis, TRG
      significantly affected disease-free survival (p = 0.03). CONCLUSIONS: pCR was
      significantly associated with high TS, high Ki67 and low EGFR expression.
      Patients with pCR have a significantly lower incidence of relapse.

PMID- 20798560
TI  - Treatment of colorectal cancer with and without bevacizumab: a phase III study.
AB  - OBJECTIVE: The objective of this phase III trial was to compare chemotherapy
      combined with bevacizumab versus chemotherapy alone in the treatment of patients
      with advanced colorectal cancer. METHODS: From September 2004 till September
      2008, 222 treatment-naive patients were enrolled and divided into 2 arms: 114 arm
      A patients were treated with leucovorin, 5-fluorouracil plus irinotecan in
      combination with bevacizumab, and 108 arm B patients were treated as above
      without bevacizumab. All patients were stage IV with histologically confirmed
      adenocarcinoma. RESULTS: The median overall survival of arm A patients was 22.0
      months (95% CI: 18.1-25.9) and 25.0 months (CI: 18.1-31.9) for arm B patients.
      There was no statistically significant difference between the 2 arms (p =
      0.1391). No statistically significant difference between the 2 arms regarding the
      response rate was observed: partial response, 42 patients (36.8%) and 38 patients
      (35.2%) for arms A and B, respectively. Hematologic toxicity did not differ in
      the comparison of the 2 arms. Nonhematologic toxicity in arm A involved
      hypertension in 23 (20.2%) of the patients and proteinuria in 7 (6.1%); 3
      patients experienced hemorrhage and 1 patient intestinal perforation. None of
      these side effects was observed in arm B patients. CONCLUSION: No statistically
      significant difference in median overall survival in patients with advanced
      colorectal cancer treated with bevacizumab plus a combination therapy (arm A) and
      those treated with the combination only, without bevacizumab (arm B), was
      observed.

PMID- 20798561
TI  - Association of genetic polymorphisms in STAT1 gene with increased risk of
      hepatocellular carcinoma.
AB  - OBJECTIVE: Although signal transducer and activator of transcription 1 (STAT1), a
      transcription factor, plays a critical role in carcinogenesis and has been
      implicated as a tumor suppressor, few studies have investigated the associations
      between polymorphisms of this gene and the risk of cancer development. The aim of
      this study was to examine whether STAT1 gene polymorphisms are associated with
      the risk of hepatocellular carcinoma (HCC). METHODS: Ten single nucleotide
      polymorphisms in the STAT1 gene were genotyped by TaqMan assays in 469 HCC cases
      and 558 age-, sex- and HBsAg-matched controls in a Chinese population. RESULTS:
      Minor allele homozygous genotypes at rs867637 (9,046 bp 3' of STP A>G), rs3771300
      (IVS24-153T>G), and rs2280235 (IVS20-103G>A), compared with their homozygote
      genotypes of common alleles, were associated with 1.6- (95% CI 1.1-2.3), 1.6-
      (95% CI 1.1-2.4), and 1.4-fold (95% CI 0.95-1.9) increased risk of HCC,
      respectively. The GGA haplotype, comprised of risk alleles at rs867637, rs3771300
      and rs2280235, conferred a 1.2-fold (95% CI 1.0-1.5) increased risk of HCC, as
      compared to the most common haplotype of ATG. Diplotype GGA/GGA conferred a 1.6
      fold (95% CI 1.0-2.5) increased risk of HCC compared with diplotype ATG/ATG.
      CONCLUSION: Our results demonstrate for the first time that polymorphisms in the
      STAT1 gene are associated with HCC susceptibility.

PMID- 20798562
TI  - Improved overall survival with 12 cycles of single-agent paclitaxel maintenance
      therapy following a complete response to induction chemotherapy in advanced
      ovarian carcinoma.
AB  - OBJECTIVES: Previously reported studies have suggested that maintenance therapy
      in the treatment of ovarian cancer may provide progression-free survival (PFS)
      benefits, although they have not discerned a similar impact on patient overall
      survival (OS). METHODS: We examined the long-term PFS and OS of a previous study
      population consecutively treated with either 3 cycles (group A; n = 13 patients)
      or 12 cycles (group B; n = 13) of paclitaxel (135 mg/m(2); Q21 days) maintenance
      therapy. Eligible patients received maintenance chemotherapy following a complete
      response to 6 cycles of primary induction chemotherapy, comprising 6 cycles of
      carboplatin (AUC = 5), paclitaxel (175 mg/m(2)), and gemcitabine (800 mg/m(2))
      per protocol. RESULTS: There were statistically significant PFS differences
      between group A (12 months) and group B (24 months) (p = 0.016). Moreover, the OS
      in group A was 38 months and 80 months for group B (p = 0.012). Current follow-up
      for this patient population exceeds 58 months. CONCLUSIONS: In the present
      investigation, 12 cycles of single agent paclitaxel maintenance therapy were
      associated with improved patient PFS and OS benefits. Despite contradictory
      reports, paclitaxel-based maintenance therapy may favorably impact both PFS and
      OS in advanced ovarian cancer patients who obtain a complete response to primary
      induction chemotherapy.

PMID- 20798563
TI  - Effect of hypothyroidism on postnatal conjunctival development in rats.
AB  - AIM: To study the conjunctival development in hypothyroid genetically epilepsy
      prone rats (GEPRs) with serum T3 and T4 significantly lower than in normal rats.
      METHODS: A structural, ultrastructural and histochemical study on the
      conjunctival epithelium of GEPRs and of control Sprague-Dawley (SD) rats before
      and after eyelid opening, with particular regard to goblet cell differentiation.
      RESULTS: From birth to day 12, no goblet cells were demonstrated on the
      conjunctival surface of both strains, so that the epithelium was formed only by a
      cuboidal basal layer and by a superficial layer of roundish or flattened cells.
      On day 16, after the eyelid opening, Alcian blue (AB)-positive goblet cells
      filled with homogeneous granules were demonstrated isolated, in GEPRs, or
      clustered, in SD rats, in both the fornices and palpebral conjunctiva. The
      epithelium showed a basal layer and many layers of flattened cells and was taller
      in SD rats (8-10 layers) than in GEPRs (6-7 layers). At 3 months, the epithelium
      in SD rats was higher with generally clustered goblet cells, whilst in GEPRs
      goblet cells were both isolated or clustered. In both strains, the goblet cells
      showed a marked AB/periodic acid-Schiff positivity all over the conjunctival
      surface and were filled with granules of different density. In both strains,
      goblet cells were absent at birth and their appearance, as AB-positive cells, was
      concomitant with eyelid opening. CONCLUSIONS: Hypothyroid rats showed a
      conjunctival development different than that of normothyroid rats for both
      epithelial and goblet cells. It appears that thyroid hormone imbalance may
      influence conjunctival development.

PMID- 20798564
TI  - Long-term evaluation of Cochlear implantation in Cogan syndrome.
AB  - PURPOSE: The evaluation of long-term results of cochlear implantation in patients
      with typical Cogan syndrome. PROCEDURES: The medical records of approximately
      3,000 patients who underwent cochlear implantation in a tertiary centre within
      the period 1992-2007 were retrospectively examined. RESULTS: Four cochlear
      implant recipients with Cogan syndrome (6 implantations) were identified. One
      cochlea was found to be partially obliterated; the electrode could, however, be
      completely inserted. Wound healing disorders and infections in a patient with
      systemic symptoms were the only postoperative complications. Hearing outcome was
      favorable, with average HSM and monosyllabic scores of 96.7 and 82.5%,
      respectively, in an average follow-up time of 9.25 years. CONCLUSIONS: Cochlear
      implantation is the appropriate hearing rehabilitation method in Cogan syndrome
      patients. Although the basic illness does not affect the long-term hearing
      outcome, skin-atrophy-related complications in cases with systemic symptoms may
      occur. Finally, the cochlear implant surgeon should be aware of the possible
      cochlea obliteration.

PMID- 20798565
TI  - Postoperative recurrence as an associated factor of malignant transformation of
      oral dysplastic leukoplakia.
AB  - PURPOSE: To evaluate the clinically associated factors of malignant
      transformation in patients who received laser surgery for oral dysplastic
      leukoplakia. PROCEDURES: The clinicopathological data of patients receiving laser
      surgery for dysplastic leukoplakia from 2002 to 2008 and HPV genomic DNA
      extracted from paraffin-embedded specimens were analyzed statistically. RESULTS:
      A total 114 patients, 90 males and 24 females with an average age of 49.7 +/-
      12.2 years were enrolled. The follow-up period ranged from 1.07 to 7.43 years
      (mean 3.4 +/- 1.3 years). Thirteen cases had malignant transformation (11.4%).
      Multiple-focus lesions, non-homogeneous leukoplakia, high-grade dysplasia and
      recurrence after laser treatment were significant factors in univariate analysis.
      Multivariate analysis showed that recurrence (relative risk = 9.40) was the
      independent prognostic factor for malignant transformation. CONCLUSIONS:
      Recurrence after laser treatment is an independent prognostic factor predicting
      malignant transformation of dysplastic oral leukoplakia.

PMID- 20798566
TI  - Laryngeal tremor: co-occurrence with other movement disorders.
AB  - INTRODUCTION: Limited epidemiologic information exists regarding the co
      occurrence of laryngeal tremor (LT) and tremor in other parts of the body, and of
      other movement disorders. Tremor is the involuntary skeletal muscle contraction
      that leads to oscillatory movement. It can affect many parts of the body
      including the chin, neck, laryngeal muscles, or limbs. When it is not associated
      with parkinsonism, it is called an essential tremor. We reviewed our 5-year
      experience with LT patients and the presence of other movement disorders.
      METHODS: We performed a retrospective review of 29 patients with LT seen in a
      voice clinic over a 5-year period from January 2004 to April 2009. RESULTS: Of
      the 29 patients, 27 (93%) had co-incidence of another movement disorder. Of these
      patients, 45% had spasmodic dysphonia, 41% had oropharyngeal tremors, 38% had
      essential limb tremor, 31% had orofacial dystonias, and 24% had essential head
      and neck tremor. Only 1 patient (3%) presented with Parkinson's disease.
      CONCLUSION: Otolaryngologists may be the first to evaluate a patient for tremors.
      It is important to consider other movement disorders when examining these
      patients as neurologic assessment and treatment of other tremors may be
      beneficial.

PMID- 20798567
TI  - The role of the spectral and temporal cues in consonantal vocalization and glide
      insertion.
AB  - This study investigates the perceptual role of several acoustic characteristics
      to glide generation processes affecting the consonants [t], [beta] and [eta],
      i.e., the vocalization of syllable-final [t] and syllable-initial [beta] into
      [w], and the insertion of [j] before syllable-final [eta]. Results from
      identification tests with synthetic speech stimuli performed on Catalan-speaking
      informants reveal that both the formant frequency characteristics (at the
      consonant steady-state period for [t] and [beta], and at the endpoint of the
      vowel transitions for [eta]), and the onset or onset/offset time of the vowel
      transitions may play an active role in vocalization and glide insertion. Mostly
      for the changes [t] > [w] and [eta]> [jeta], glide identification was triggered
      by formant frequency variations rather than by variations in the temporal
      implementation of the vowel transitions. The implications of the perception
      results for the interpretation of the sound changes of interest are evaluated.

PMID- 20798568
TI  - Relational timing in the production and perception of Japanese singleton and
      geminate stops.
AB  - This work examines the production and perception of the Japanese singleton versus
      geminate stop contrast in order to investigate properties that distinguish the
      contrast in the face of variability due to speech rate. The acoustic study found
      two local relational durations, the ratio of the stop to the preceding mora and
      the ratio of the stop to the following vowel, to be stable across speaking rates
      and to accurately classify singleton and geminate productions. However, the
      subsequent perception study demonstrated an influential role of the preceding
      mora duration and a marginal role of the following vowel duration on listeners'
      categorization. These results demonstrate that Japanese listeners can take
      advantage of relative duration in the perception of the stop length contrast, and
      that relative strength of simultaneously available acoustic cues does not
      necessarily translate into equal perceptual importance.

PMID- 20798569
TI  - Coordinating voicing onset with articulation: a potential role for sensory cues
      in shaping phonological distinctions.
AB  - In the typical speech of any language, voicing onset and offset are effortlessly
      coordinated with articulation as part of the intrinsic coordination of sound
      production. In this paper, we argue that voicing-articulatory coordination
      patterns could be shaped by sensory feedback during early speech learning and
      these patterns persist in mature syllable productions. Our experimental results
      show that voicing onset is closely associated with the peak velocity and peak
      amplitude of jaw and upper lip movements for VC syllables in adults. This robust
      coordination in the onset position may function to increase the salience of VC
      syllables and provide a phonetically natural explanation for vowels to undergo
      phonological lengthening and to avoid phonological reduction in word-initial
      onset position.

PMID- 20798570
TI  - Pitch range variation in English tonal contrasts: continuous or categorical?
AB  - The importance of pitch range variation for intonational meaning and theory is
      well known; however, whether pitch range is a phonetic dimension which is treated
      categorically in English remains unclear. To test this possibility, three
      intonation continua varying in pitch range were constructed which had endpoints
      with contrastive representations under autosegmental-metrical (AM) theory: H* vs.
      L+H*, H* with 'peak delay' vs. L*+H, and %H L* vs. L*. The prediction derived
      from AM theory was that the reproduction of continuous pitch range variation
      should show a discrete pattern reflecting a change in the phonological
      representation of tonal sequences and in the number of tonal targets across each
      continuum. Participants' reproductions of each stimulus set showed continuous
      variation in pitch range, suggesting that pitch range is a gradient phonetic
      dimension in English conveying semantic contrast, similar to the formant space
      for vowels. Moreover, the gradience observed in productions across all parts of
      the pitch range suggests that contours within each series had the same number of
      tonal targets. The results support a version of AM theory in which rises and
      falls are usually comprised of two tonal targets, with strictly monotonic f(0)
      interpolation between them.

PMID- 20798571
TI  - Linguistic and human effects on F(0) in a tonal dialect of Qiang.
AB  - While both human and linguistic factors affect fundamental frequency (F(0)) in
      spoken language, capturing the influence of multiple effects and their
      interactions presents special challenges, especially when there are strict time
      constraints on the data-gathering process. A lack of speaker literacy can further
      impede the collection of identical utterances across multiple speakers. This
      study employs linear mixed effects analysis to elucidate how various effects and
      their interactions contribute to the production of F(0) in Luobuzhai, a tonal
      dialect of the Qiang language. In addition to the effects of speaker sex and
      tone, F(0) in this language is affected by previous and following tones, sentence
      type, vowel, position in the phrase, and by numerous combinations of these
      effects. Under less than ideal data collecting conditions, a single experiment
      was able to yield an extensive model of F(0) output in an endangered language of
      the Himalayas.

PMID- 20798572
TI  - The transmission of meaning by prosodic phrasing. A comparison of French with
      english and german using no ls and hs.
AB  - This paper examines the relationship between phonetic exponents of syntagmatic
      prosodic structuring and functions in speech communication in English, German,
      and French. Two strands are distinguished in this substance-function relation:
      the transmission of semantic structures in propositional, appellative, and
      expressive meaning, and the facilitation of this transfer from sender to receiver
      by rhythmic organization. Bundles of several weighted feature values contribute
      to the signalling of hierarchies of prosodic phrasing to map semantic and
      rhythmic structures for communicative effect. French and the Germanic languages
      differ more specifically in the rhythmic strand.

PMID- 20798573
TI  - Helmut Rennert's universal genesis of endogenous psychoses: the historical
      concept and its significance for today's discussion on unitary psychosis.
AB  - Next to Karl Leonhard (1904-1988), Helmut Rennert (1920-1994) was the
      internationally best known representative of psychiatry from the former German
      Democratic Republic (GDR). He rose to prominence above all through his model of
      the universal genesis of endogenous psychoses, which constituted an antithesis to
      Leonhard's differentiated division. The 'polar opposite' aspects of Rennert and
      Leonhard are represented with an emphasis on their contrasting views of
      psychiatric nosology. In this respect, Rennert's model conceptions constitute the
      primary focus of attention. The fact that both concepts continue to possess
      topical perspectives to this day is reflected in the current discussion regarding
      nosological, categorical, syndromatological and dimensional approaches in
      relation to the further development of the classification systems of mental
      disorders. The preparatory work on the future classification systems will
      potentially omit the dichotomy between schizophrenic and affective disorders.
      These endeavors are in accordance with Rennert's unitarian psychopathological
      view and support his acceptance of the psychopathological continuity from
      affective to schizophrenic syndromes. The current discussion concerning the
      future classification is in line with Rennert, whose aim was to provide an
      unconventional model that unites findings from the different fields of
      psychiatric research. The classification of mental disorders without a previous
      establishment on the basis of fundamental theoretical assumptions could certainly
      foster a dynamic development in the future. A differentiated knowledge of the
      history of the ideas of unitary psychosis and their further development might be
      helpful in this development and can be of particular use when critically
      questioning explanatory approaches that are prone to simplification.

PMID- 20798574
TI  - Schizophrenia psychopathology in a Kuwaiti Arab sample.
AB  - BACKGROUND: The heterogeneity of schizophrenia psychopathology has led to a
      search for symptom clusters that could be related to broad features of the
      disease. The objectives of the study were to: (1) highlight the pattern of
      symptoms among Kuwaiti subjects with schizophrenia, using the ICD-10 symptom
      checklist; (2) assess the factor structure of the Brief Psychiatric Rating Scale
      18 (BPRS-18) and BPRS-24, and (3) evaluate the relationship of the resulting
      factors with sociodemographic characteristics, age at onset of illness, family
      history of mental illness, objective indicators of quality of life, self-esteem,
      affect balance, family caregiver burden, patient's perceptions of service
      satisfaction and needs for care. METHOD: Consecutive outpatients in stable
      condition were assessed with the BPRS and ICD-10 symptom checklist, as well as
      measures of quality of life, needs for care, service satisfaction and family
      caregiver burden. RESULTS: There were 130 patients (66.1% men, mean age = 36.8
      years, age at onset of illness = 24.2 years, duration of illness = 12.9 years).
      Of the ICD-10 symptoms, the commonest positive symptoms were hallucinations
      (58.5%) and delusions (72%). Catatonic symptoms were rare (2.9%). About a quarter
      of the subjects experienced 4 of the negative symptoms. In exploratory factor
      analysis, we broadly replicated the known syndromes for BPRS-24 (disorganization,
      positive, activation, manic, negative and depression) and BPRS-18 (negative,
      positive, activation and affect). In regression analyses, the variables
      independently associated with psychopathology were family income, negative
      affect, self-esteem, duration of illness, age, lack of money for enjoyment, met
      needs for care and caregiver tension. The negative syndrome had more significant
      associations with the variables investigated than the positive syndrome.
      Psychopathological scores were separable from indices of psychological well
      being. CONCLUSION: In this first study of schizophrenia psychopathology from the
      Arab world, the clinical manifestations were similar to the data from the
      developed countries. The persistence of psychotic symptoms despite freely
      available antipsychotic treatment and the impact on caregiver burden call for
      attention to the perennial issue of treatment resistance and underscore the need
      for continued interaction with family members after the acute inpatient phase of
      treatment, in order to address the impact of symptoms.

PMID- 20798575
TI  - Autism and perplexity: a qualitative and theoretical study of basic subjective
      experiences in schizophrenia.
AB  - BACKGROUND: Autistic traits and perplexity are considered core features of
      schizophrenia in phenomenological psychiatry. They express a fundamental
      disturbance of the self-world relation (including disturbances of self and
      intersubjectivity). The aim of our study was to examine this disturbance by
      exploring in detail how autism and perplexity are experienced subjectively.
      METHODS: It is a qualitative single-case study. In order to fully examine our
      patient's experiences within the context of his experiential world and not only
      as isolated or decontextualized symptoms, we applied a heideggerian framework,
      i.e. Heidegger's exhaustive account of the self-world relation (care). RESULTS:
      Through the framework of care, we discovered a profound disturbance of the self
      world relation in our patient, characterized by subtle experiences of
      estrangement, anxiety and exposure. We found these experiences to be enduring,
      pervasive and generative for the development of other symptoms. CONCLUSIONS: We
      argue that these experiences can be seen as experiential correlates of schizotypy
      and of vulnerability to schizophrenia, and furthermore that an understanding of
      these experiences can play a role in diagnostic and differential diagnostic
      procedures, e.g. in early detection or in the search for high-risk individuals,
      as well as in the psychotherapy of schizophrenia.

PMID- 20798576
TI  - Patients with borderline personality disorder not participating in an RCT: are
      they different?
AB  - BACKGROUND: Despite the notion that randomized controlled trials are regarded as
      the gold standard in psychotherapy research, questions about their
      generalizability have been raised. This paper focuses on the differences between
      participants and eligible nonparticipants of a randomized controlled trial for
      patients with borderline personality disorder (BPD). SAMPLING AND METHODS: One
      hundred forty-two patients were screened, and 122 were found eligible for study
      participation. Out of these, 64 patients (52.5%) gave informed consent and were
      included in the study. RESULTS: The 58 eligible nonparticipants showed a lower
      level of functioning (global assessment of functioning score), had a history of
      more outpatient treatment attempts and were living alone more often. Regarding
      acute symptoms and severity of BPD as indexed by suicide attempts, inpatient
      treatments, substance abuse and history of trauma, no differences between the
      groups could be detected. Moreover, participants showed significantly more eating
      disorders, whereas nonparticipants presented more affective and anxiety
      disorders. CONCLUSIONS: The results indicate that lower psychosocial functioning
      and comorbid affective and anxiety disorders decrease BPD patients' willingness
      to participate in an RCT.

PMID- 20798577
TI  - A new ColE1-like plasmid group revealed by comparative analysis of the
      replication proficient fragments of Vibrionaceae plasmids.
AB  - Plasmids play important roles in horizontal gene transfer among Vibrionaceae, but
      surprisingly little is known about their replication and incompatibility systems.
      In this study, we successfully developed a bioinformatics-assisted strategy of
      experimental identification of 7 Vibrio plasmid replicons. Comparative sequences
      analysis of the 7 Vibrio plasmid replicons obtained in this study together with 8
      published Vibrionaceae plasmid sequences revealed replication participating
      elements involved in the ColE1-mode of replication initiation and regulation.
      Like plasmid ColE1, these Vibrionaceae plasmids encode two RNA species (the
      primer RNA and the antisense RNA) for replication initiation and regulation and,
      as a result the 15 Vibrionaceae plasmids were designated as ColE1-like
      Vibrionaceae (CLV) plasmids. Two subgroups were obtained for the 15 CLV plasmids
      based on comparison of replicon organization and phylogenetic analysis of
      replication regions. Coexistence of CLV plasmids has been demonstrated by direct
      sequencing analysis and southern hybridization, strongly suggesting that the
      incompatibility of CLV plasmids is determined mainly by the RNAI species like the
      ColE1-like plasmids. Sequences resembling the conserved Xer recombination sites
      were also identified on the CLV plasmids, indicating that the CLV plasmids
      probably use the host site-specific recombination system for multimer resolution
      like that used by ColE1-like plasmids. All the results indicated that the 15
      plasmids form a new ColE1-like group, providing basis for rapid characterization
      and classification of Vibrionaceae plasmids.

PMID- 20798578
TI  - A monoclonal antibody that specifically binds chitosan in vitro and in situ on
      fungal cell walls.
AB  - We report the generation of the first monoclonal antibody that specifically binds
      to the polysaccharide chitosan. Mice were immunized with a mixture of chitosans,
      and hybridoma clones were screened for specific binders resulting in the
      isolation of a single clone secreting a chitosan-specific IgM, mAbG7. In ELISAs,
      the antibody can bind to chitosans of varying composition, but demonstrates the
      highest affinity for chitosans with lower degrees of acetylation (DA) and very
      poor binding to chitin. We tested the ability of the antibody to bind to chitosan
      in situ, using preparations of fungal cell walls. Immunofluorescence microscopy
      confirmed that the antibody bound strongly to the cell walls of fungi with high
      levels of chitosan, whereas poor staining was observed in those species with cell
      walls of predominantly chitin or cellulose. The potential use of this antibody
      for the detection of fungal contamination and the protection of plants against
      fungal pathogens is discussed.

PMID- 20798579
TI  - Membrane perturbation induced by papiliocin peptide, derived from Papilio xuthus,
      in Candida albicans.
AB  - Previously, papiliocin was isolated from the swallowtail butterfly Papilio xuthus
      and its antimicrobial activity was suggested. In this study, the antifungal
      mechanism of papiliocin was investigated against Candida albicans. Confocal laser
      scanning microscopy (CLSM) and 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence
      analysis indicated that papiliocin disturbed the fungal plasma membrane.
      Moreover, the assessment of the release of FITC-dextran (FD) from liposome
      further demonstrated that the antifungal mechanism of papiliocin could have
      originated from the pore-forming action and that the radius of the pores was
      presumed to be anywhere from 2.3 nm and 3.3 nm.

PMID- 20798580
TI  - Hydoroxyhibiscone A, a novel human neutrophil elastase inhibitor from Hibiscus
      syriacus.
AB  - In an ongoing investigation of compounds from natural products that exhibit anti
      aging properties, hydroxyhibiscone A (1), a new furanosesquiterpenoid, together
      with hibiscone D (2), was isolated from the root bark of Hibiscus syriacus.
      Utilizing UV, IR, NMR, and MS spectroscopic analyses, these chemical structures
      were revealed. Compounds 1 and 2 were found to possess significant anti-aging
      properties on the human neutrophil elastase (HNE) assay, exhibiting HNE
      inhibitory activities with IC50 values of 5.2 and 4.6 micronM, respectively.

PMID- 20798581
TI  - Influence of the hydrophobic amino acids in the N- and C-terminal regions of
      pleurocidin on antifungal activity.
AB  - To investigate the influence of N- or C-terminal regions of pleurocidin (Ple)
      peptide on the antifungal activity, four analogues partially truncated in the N-
      or C-terminal regions were designed and synthesized. Circular dichroism (CD)
      spectroscopy demonstrated that all the analogues maintained an alpha-helical
      structure. The antifungal susceptibility testing also showed that the analogues
      exhibited antifungal activities against human fungal pathogens, without hemolytic
      effects against human erythrocytes. The result further indicated that the
      analogues had discrepant antifungal activities (Ple > Ple (1-22) > Ple (4-25) >
      Ple (1-19) > Ple (7-25)) and that N-terminal deletion affected the activities
      much more than C-terminal deletion. Hydrophobicity (Ple > Ple (1-22) > Ple (4-25)
      > Ple (1-19) > Ple (7-25)) was thought to have been one of the consistent factors
      that influenced these activity patterns, rather than the other primary factors
      like the helicity (Ple > Ple (4-25) > Ple (1-22) > Ple (1-19) > Ple (7-25)) or
      the net charge (Ple = Ple (4-25) = Ple (7-25) > Ple (1-22) = Ple (1-19)) of the
      peptides. Taken together, the hydrophobic amino acids in the N-terminal region of
      Ple is more crucial for the antifungal activity than those in the C-terminal
      region.

PMID- 20798582
TI  - Towards methionine overproduction in Corynebacterium glutamicum--methanethiol and
      dimethyldisulfide as reduced sulfur sources.
AB  - In the present work, methanethiol and dimethyldisulfide were investigated as
      sulfur source for methionine synthesis in Corynebacterium glutamicum. In silico
      pathway analysis has predicted a high methionine yield for these reduced
      compounds provided that they can be utilized. Wild type cells were able to grow
      on methanethiol and on dimethyldisulfide as sole sulfur source, respectively.
      Isotope labeling studies with mutant strains exhibiting targeted modification of
      methionine biosynthesis gave detailed insight into the underlying pathways
      involved in assimilation of methanethiol and dimethyldisulfide. Both sulfur
      compounds are incorporated as entire molecule, adding the terminal S-CH3 group to
      O-acetylhomoserine. In this reaction, methionine is directly formed. MetY (O
      acetylhomoserine sulfhydrylase) was identified as enzyme catalyzing this
      reaction. Deletion of metY resulted in methionine auxotrophic strains grown on
      methanethiol or dimethyldisulfide as sole sulfur source. Plasmid based
      overexpression of metY in the delta metY background restored the capability to
      grow on methanethiol or dimethyldisulfide as sole sulfur source. In vitro studies
      with the C. glutamicum wild type revealed a relatively low activity of MetY for
      methanethiol (63 mU/mg) and dimethyldisulfide (61 mU/mg). Overexpression of metY
      increased the in vitro activity to 1780 mU/mg and was beneficial for methionine
      production, since the intracellular methionine pool was increased two-fold in the
      engineered strain. This positive effect was limited by depletion of the metY
      substrate O-acetylhomoserine, requesting for further metabolic engineering
      targets towards competitive production strains.

PMID- 20798583
TI  - Antimicrobial activities of 1,4-benzoquinones and wheat germ extract.
AB  - We evaluated the antibacterial activities of selected edible Korean plant seeds
      against the food-borne pathogens Staphylococcus aureus KCTC1927, Escherichia coli
      KCTC2593, Salmonella typhimurium KCTC2054, and Bacillus cereus KCTC1014. While
      screening for antibacterial agents, we discovered that wheat germ extract
      contains 2,6-dimethoxy-1,4-benzoquinone (DMBQ) and is highly inhibitory to S.
      aureus and B. cereus. This is the first report of the antibacterial activity of
      wheat germ extract. We also investigated the antibacterial activities of the 1,4-
      benzoquinone standards 1,4-benzoquinone (BQ), hydroquinone (HQ),
      methoxybenzoquinone (MBQ), and 2,6-dimethoxy- 1,4-benzoquinone (DMBQ). DMBQ and
      BQ were the most highly inhibitory to S. aureus and S. typhimurium, followed by
      MBQ and HQ. MICs for DMBQ and BQ ranged between 8 and 64 microgram/ml against the
      four foodborne pathogens tested. DMBQ and BQ showed significant antibacterial
      activity; the most sensitive organism was S. aureus with an MIC of 8
      microgram/ml. BQ exhibited good activity against S. typhimurium (32 microgram/ml)
      and B. cereus (32 microgram/ml). The results suggest that wheat germ extract has
      potential for the development of natural antimicrobials and food preservatives
      for controlling foodborne pathogens.

PMID- 20798584
TI  - Identification and distribution of Bacillus species in doenjang by whole-cell
      protein patterns and 16S rRNA gene sequence analysis.
AB  - Many bacteria are involved in fermentation of doenjang and Bacillus species are
      known to perform significant roles. Although the SDS-PAGE technique has been
      frequently used for classification and identification of bacteria in various
      samples, there has been no investigation of the microbial diversity in doenjang.
      This study aims to investigate the identification and distribution of dominant
      Bacillus species in doenjang using SDS-PAGE profiles of whole cell proteins and
      16S rDNA sequencing. SDS-PAGE of whole cell proteins of the reference Bacillus
      strains yielded differential banding patterns that could be considered to be
      highly specific fingerprints. Bacterial strains isolated from doenjang samples
      were grouped using whole cell protein patterns, which were confirmed by the
      analysis of 16S rDNA sequencing. B. subtilis was found to be the most dominant
      strain in most of the samples, and B. licheniformis and B. amyloliquefaciens were
      less frequently detected. The results obtained in this study showed that a
      combined identification method, SDS-PAGE patterns of whole cell proteins and
      subsequent 16S rDNA sequence analysis, could successfully identify Bacillus
      species isolated from doenjang.

PMID- 20798585
TI  - Heterologous production of pediocin PA-1 in Lactobacillus reuteri.
AB  - The recombinant DNA pLR5cat_PSAB in which pediocin PA-1 structural and immunity
      genes (pedAB) fused with the promoter and deduced signal sequence of an alpha
      amylase gene from a bifidobacterial strain were inserted in pLR5cat, an
      Escherichia coli-lactobacilli shuttle vector was transferred to Lactobacillus
      reuteri KCTC 3679 and the transformant presented bacteriocin activity. The
      recombinant L. reuteri KCTC 3679 transformed with the shortened pLR5cat(S)_PSAB,
      where non-essential region for the lactobacilli replicon was removed, also showed
      bacteriocin activity. The molecular mass of the secreted pediocin PA-1 from the
      recombinant bacteria was the same as that of native pediocin PA-1 (~4.6 kDa) from
      Pediococcus acidilactici K10 on a sodium dodecylsulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) gel. In co-cultures with Listeria monocytogenes, the
      recombinant L. reuteri KCTC 3679 effectively reduced the viable cell count of the
      pathogenic bacterium by a 3 log scale compared with a control where L.
      monocytogenes was incubated alone.

PMID- 20798586
TI  - Isolation of NH4+-tolerant mutants of Actinobacillus succinogenes for succinic
      acid production by continuous selection.
AB  - Actinobacillus succinogenes, a typical succinic acid producing microorganism, was
      inhibited seriously by ammonium ion, which hampered industrialization of A.
      succinogenes with ammonium ion based material as the pH controller. In this
      study, we have isolated an ammonium ion-tolerant mutant of A. succinogenes by
      continuous-culture technique in which all environmental factors beside the stress
      (ammonium ion) were maintained constant. In this technique, the mutant-generating
      system was not operated as a nutrient-limited chemostat, but as a nutrient
      unlimited system where cells were continuous cultured at the maximum specific
      growth rate. Mutants were isolated on agar plates containing a acid-base
      indicator bromothymol blue and high level of ammonium ion which gives 100%
      killing of the parent strain. When cultured in anaerobic bottles at ammonium ion
      concentration of 354 mmol/L, the mutant YZ0819 could produce succinic acid 40.21
      g/L with yield 80.4%, while the parent strain NJ113 did not grow. With NH4OH
      being used to buffer the culture pH in 3.0 liter stirred bioreactor, YZ0819
      produced 35.15 g/L succinic acid with yield 70.3%, 155% higher than that obtained
      by NJ113. In addition, the morphology of YZ0819 in fermentation broths was
      changed. Cells of YZ0819 were aggregated from the beginning to the end of
      fermentation. These results indicate that YZ0819 would be used to be the
      potential strain produced efficiently succinic acid with NH4OH as the pH
      controller and the formation of aggregates may be useful as an aid in the
      transferring of cells from a cultivation medium for various industrial
      applications.

PMID- 20798587
TI  - Induction of glyceollins by fungal infection in varieties of Korean soybean.
AB  - Glyceollins, one of the inducible phytoalexins produced by plants, were induced
      in a number of varieties of Korean soybean through fungal infection. Of the
      tested soybean varieties, Tae-Kwang, though not the most productive, was found to
      be currently the most suitable for the induction of glyceollins. Amongst the
      fungal species, Rhizopus microsporus var. oligosporus was seen to be the most
      effective elicitor. Halved soybean seeds produced glyceollins upon fungal
      infection; however, chopped soybeans and homogenized soybeans did not produce
      significant quantities of glyceollins.

PMID- 20798588
TI  - Effects of electrochemical reduction reactions on the biodegradation of
      recalcitrant organic compounds (ROCs) and bacterial community diversity.
AB  - Five bacterial species, capable of degrading the recalcitrant organic compounds
      (ROCs) diethyleneglycol monomethylether (DGMME), 1-amino-2-propanol (APOL), 1
      methyl-2- pyrrolidinone (NMP), diethyleneglycol monoethylether (DGMEE),
      tetraethyleneglycol (TEG), and tetrahydrothiophene 1,1-dioxide (sulfolane), were
      isolated from an enrichment culture. Cupriavidus sp. catabolized 93.5+/-1.7 mg/l
      of TEG, 99.3+/-1.2 mg/l of DGMME, 96.1+/-1.6mg/l of APOL, and 99.5+/-0.5mg/l of
      NMP in 3 days. Acineobacter sp. catabolized 100 mg/l of DGMME, 99.9+/-0.1 mg/l of
      NMP, and 100 mg/l of DGMEE in 3 days. Pseudomonas sp.3 catabolized 95.7+/-1.2
      mg/l of APOL and 99.8+/-0.3 mg/l of NMP. Paracoccus sp. catabolized 98.3+/-0.6
      mg/l of DGMME and 98.3+/-1.0 mg/l of DGMEE in 3 days. A maximum 43+/-2.0 mg/l of
      sulfolane was catabolized by Paracoccus sp. in 3 days. When a mixed culture
      composed of the five bacterial species was applied to real wastewater containing
      DGMME, APOL, NMP, DGMEE, or TEG, 92~99% of each individual ROC was catabolized
      within 3 days. However, at least 9 days were required for the complete
      mineralization of sulfolane. Bacterial community diversity, analyzed on the basis
      of the TGGE pattern of 16S rDNA extracted from viable cells, was found to be
      significantly reduced in a conventional bioreactor after 6 days of incubation.
      However, biodiversity was maintained after 12 days of incubation in an
      electrochemical bioreactor. In conclusion, the electrochemical reduction reaction
      enhanced the diversity of the bacterial community and actively catabolized
      sulfolane.

PMID- 20798589
TI  - Growth inhibition of Microcystis aeruginosa by a glycolipid-type compound from
      Bacillus subtilis C1.
AB  - We attempted to identify the compound responsible for the growth inhibition of
      Microcystis aeruginosa occurring when a culture broth of Bacillus subtilis C1 was
      added to the medium. The active compound was purified from B. subtilis C1 culture
      broth by adsorption chromatography and HPLC, and was identified as a type of
      glycolipid based on 1H NMR and MS analyses. The purified active compound
      completely inhibited the growth of M. aeruginosa at a concentration of 10
      microgram/ml. This is the first report of a glycolipid produced by a Bacillus
      strain that has potential as an agent for the selective control of bloom-forming
      M. aeruginosa.

PMID- 20798590
TI  - Cloning and expression of cDNA encoding a cysteine protease inhibitor from
      clamworm and its possible use in managing Anoplophora glabripennis Motschulsky
      (Coleoptera: Cerambycidae).
AB  - A cDNA encoding cysteine protease inhibitor (CPI) was isolated from the cDNA
      library of clamworm Perinereis aibuhitensis Grube. The deduced amino acid
      sequence analysis showed that the protein had 51%, 48%, and 48% identity with
      Zgc:153129 from Danio rerio, cystatin B from Theromyzon tessulatum and ChainA,
      stefin B tetramer from Homo sapiens, respectively. The gene was cloned into the
      intracellular expression vector pET-15b and expressed in Escherichia coli. The
      recombinant CPI (PA-CPI) was purified by affinity chromatography on Ni-charged
      resin and ion-exchange chromatography on DEAE-Sepharose FF. The relative
      molecular mass of PA-CPI was 16 KDa deduced by SDS-PAGE. Activity analysis showed
      that the recombinant protein could inhibit the proteolytic activity of papain. A
      constitutive and secretive expression vector was also constructed, and the cDNA
      encoding CPI was subcloned into the vector for extracellular expression. Western
      blotting analysis results showed that the PA-CPI was secreted into the medium.
      Bioassay demonstrated that E. coli DH5alpha harboring pUC18ompAcat-CPI showed a
      significant difference in mortality to the Asian longhorned beetle Anoplophora
      glabripennis compared with untransformed E. coli DH5alpha and control.

PMID- 20798591
TI  - Ammonium production during the nitrogen-fixing process by wild Paenibacillus
      strains and cell-free extract adsorbed on nano TiO2 particles.
AB  - During the nitrogen-fixing process, ammonia (NH3) is incorporated into glutamate
      to yield glutamine and is generally not secreted. However, in this study, NH3-
      excreting strains of nitrogen-fixing Paenibacillus were isolated from soil. The
      ammonium production by the Paenibacillus strains was assayed in different
      experiments (dry biomass, wet biomass, cell-free extract, and cell-free extract
      adsorbed on nano TiO2 particles) inside an innovative bioreactor containing
      capsules of N2 and H2. In addition, the effects of different N2 and H2 treatments
      on the formation of NH3 were assayed. The results showed that the dry biomass of
      the strains produced the most NH3. The dry biomass of the Paenibacillus strain E
      produced the most NH3 at 1.50, 0.34, and 0.27 micrometer NH3/mg biomass/h in the
      presence of N2 + H2, N2, and H2, respectively, indicating that a combined
      effluent of N2 and H2 was vital for NH3 production. Notwithstanding, a cell-free
      extract (CFE) adsorbed on nano TiO2 particles produced the most NH3 and preserved
      the enzyme activities for a longer period of time, where the NH3 production was
      2.45 micrometer/mg CFE/h over 17 h. Therefore, the present study provides a new,
      simple, and inexpensive method of NH3 production.

PMID- 20798592
TI  - Gigantic macroautophagy in programmed nuclear death of Tetrahymena thermophila.
AB  - Programmed nuclear death (PND) in Tetrahymena is a unique process during
      conjugation, in which only the parental macronucleus is degraded and then
      eliminated from the progeny cytoplasm, but other co-existing nuclei such as new
      micro- and macronuclei are unaffected. PND through autophagic elimination is
      expected to be strictly controlled, considering the significant roles in ciliates
      such as turnover of disused organelles and production of the next generation.
      Here we demonstrate that PND in Tetrahymena involves peculiar aspects of
      autophagy, which differ from mammalian or yeast macroautophagy. Drastic change of
      the parental macronucleus occurs when differentiation of new macronuclei is
      initiated. Combined use of monodansylcadaverine and a lysosome indicator
      LysoTracker Red showed that prior to nuclear condensation, the envelope of the
      parental macronucleus changed its nature as if it is an autophagic membrane,
      without the accumulation of a pre-autophagosomal structure from the cytoplasm.
      Subsequently, lysosomes approached only to the parental macronucleus and
      localized at the envelope until a final resorption stage. In addition, we found
      that the parental macronucleus exhibits certain sugars and phosphatidylserine on
      the envelope, which are possible "attack me" signals, that are not found on other
      types of nuclei. These findings suggest that PND is a highly elaborated process,
      different from the typical macroautophagy seen in other systems, and is executed
      through interaction between specific molecular signals on the parental
      macronuclear envelope and autophagic/lysosomal machineries.

PMID- 20798593
TI  - Use of dabigatran etexilate to reduce breast cancer progression.
AB  - Coagulation proteases and the generation of thrombin are increased in breast
      tumor epithelial and stromal cells. Since thrombin can modify tumor cell behavior
      directly through the activation of protease-activated receptors (PARs) or
      indirectly by generating fibrin matrices, the effect of dabigatran etexilate, a
      direct thrombin inhibitor, on breast cancer development was evaluated. Dabigatran
      inhibited invasiveness of MDA-MB-231 breast carcinoma cells across Matrigel
      coated membranes at concentrations that had no effect on the proliferation index
      of cultured tumor cells. In vivo evaluation of invasiveness of MDA-MB-231 cells
      in tracheal xenotransplants in nude mice orally administered dabigatran etexilate
      twice daily at a dose of 45 mg/kg over 4 weeks demonstrated less invasion of
      tumor cells through the tracheal wall compared to vehicle-treated mice. To
      evaluate the effect of dabigatran on the development of metastatic foci, 4T1
      tumor cells were injected orthotopically in the mammary fat pads of syngeneic
      Balb/c mice. Dabigatran etexilate treatment exhibited evidence of antitumor
      activity with a 50% reduction in tumor volume at 4 weeks following orthotopic
      injection of 4T1 cells in syngeneic Balb/c mice with no weight loss in treated
      mice. Dabigatran etexilate reduced both 4T1 tumor cells in the blood and liver
      micrometastases by 50-60%. These results suggest that oral administration of the
      direct thrombin inhibitor, dabigatran etexilate, inhibits both invasion and
      metastasis of malignant breast tumors, suggesting that it may be beneficial in
      not only preventing thrombotic events in cancer patients, but also as adjunct
      therapy to treat malignant tumors.

PMID- 20798594
TI  - Hormonal regulation of Drosophila microRNA let-7 and miR-125 that target innate
      immunity.
AB  - The steroid 20-hydroxy-ecdysone (20-HE) and the sesquiterpenoid Juvenile Hormone
      (JH) coordinate insect life stage transitions. 20-HE exerts these effects by the
      sequential induction of response genes. In the nematode Caenorhabditis elegans
      hormones also play a role in such transitions, but notably, microRNA such as let
      7 and lin-4 have likewise been found to help order developmental steps. Little is
      known about the corresponding function of homologous microRNA in Drosophila
      melanogaster, and the way microRNA might be regulated by 20-HE in the fly is
      ambiguous. Here we used Drosophila S2 cells to analyze the effects of 20-HE on D.
      melanogaster microRNA let-7 and miR-125, the homolog of lin-4. The induction by
      20-HE of let-7 and miR-125 in S2 cells is inhibited by RNAi knockdown of the
      ecdysone receptor and, as previously shown, by knockdown of its cofactor broad
      complex C. To help resolve the currently ambiguous role of 20-HE in the control
      of microRNA, we show that nanomolar concentrations of 20-HE primes cells to
      subsequently express microRNA when exposed to micromolar levels of 20-HE. We then
      explore the role microRNA plays in the established relationship between 20-HE and
      the induction of innate immunity. We show that the 3'UTR of the antimicrobial
      peptide diptericin has a let-7 binding site and that let-7 represses translation
      from this site. We conclude that 20-HE facilitates the initial expression of
      innate immunity while it simultaneously induces negative regulation via microRNA
      control of antimicrobial peptide translation.

PMID- 20798595
TI  - Time to taste: circadian clock function in the Drosophila gustatory system.
AB  - Circadian clocks keep time in the digestive, circulatory, reproductive, excretory
      and nervous systems even in absence of external cues. Central oscillators in the
      brain control locomotor activity of organisms ranging from fruit flies to man,
      but the functions of the clocks in peripheral nervous system are not well
      understood. The presence of autonomous peripheral oscillators in the major taste
      organ of Drosophila, the proboscis, prompted us to test whether gustatory
      responses are under control of the circadian clock. We find that synchronous
      rhythms in physiological and behavioral responses to attractive and aversive
      tastants are driven by oscillators in gustatory receptor neurons (GRNs); primary
      sensory neurons that carry taste information from the proboscis to the brain.
      During the middle of the night, high levels of G protein-coupled receptor kinase
      2 (GPRK2) in the GRNs suppresses tastant-evoked responses. Flies with disrupted
      gustatory clocks are hyperphagic and hyperactive, recapitulating behaviors
      typically seen under the stress of starvation. Temporal plasticity in innate
      behaviors should offer adaptive advantages to flies. In this Extra View article
      we discuss how oscillators inside GRNs regulate responsiveness to tastants and
      influence feeding, metabolism and general activity.

PMID- 20798596
TI  - RHO methylation matters: a role for isoprenylcysteine carboxylmethyltransferase
      in cell migration and adhesion.
AB  - Numerous proteins involved in diverse aspects of cell biology undergo a process
      of post-translational modification termed prenylation. The prenylation pathway
      consists of three enzymatic steps, the final of which is methylation of the
      carboxyl-terminal prenylcysteine formed in the first two steps by the enzyme
      isoprenylcysteine carboxylmethyltransferase (Icmt). Due to the prevalence of
      prenylated proteins in cancer biology, and the findings that several of the
      proteins are involved in processes controlling cell migration and adhesion, we
      sought to examine the role of Icmt - mediated methylation on cell behavior
      associated with metastasis. We found that inhibition of methylation reduces
      migration of the highly metastatic MDA-MB-231 breast cancer cell line. In
      addition, cell adhesion and cell spreading were also impaired by Icmt inhibition.
      Further investigation revealed that inhibition of Icmt significantly decreased
      the activation of both RhoA and Rac1, which are both prenylated proteins. The
      data obtained were consistent with the decreased activation being due to an
      increase in Rho GDP-dissociation inhibitor (GDI) binding by both proteins in the
      absence of their methylation. Importantly, the addition of exogenous RhoA or Rac1
      to cells in which Icmt was inhibited was able to partially, but selectively,
      rescue directed and random migration, respectively. These results establish a
      role for Icmt-mediated methylation in cell migration, and point to specific
      prenylated proteins involved in this biology. The prenylation pathway has been
      targeted for oncogenic therapies, but the role of methylation in cell motility
      had been largely unexplored until now. The finding that methylation of Rho family
      members impacts on a specific component of their function provides an additional
      avenue through which to interrogate the biology of this important class of
      regulatory proteins.

PMID- 20798597
TI  - Arabidopsis CPK3 plays extensive roles in various biological and environmental
      responses.
AB  - Plant Ca(2+)-dependent protein kinase (CPK) signaling is involved in a wide array
      of intracellular signaling pathways involved in stomatal movement and plant
      adaptation to various environmental challenges including drought, salt and cold
      stress. Arabidopsis CPK3 appears to be extensively involved in such a wide range
      of aspects, and has been shown to function in mediating the signaling following
      Ca(2+) influx after insect herbivory. The results reveal the involvement of CPK3
      in the herbivory-induced signaling network through phosphorylating the substrate
      target HsfB2a (heat shock transcription factor) for transcriptional activation of
      the plant defensin gene PDF1.2. Proteomic studies based on the cell-free protein
      production system allowed us to mine CPK3 targets more extensively and clarify
      the nature of multifunctional CPK3.

PMID- 20798598
TI  - Cellular uptake, retention and bioabsorption of HO-3867, a fluorinated curcumin
      analog with potential antitumor properties.
AB  - Curcumin, a naturally-occurring compound found in the rhizome of Curcuma longa
      plant, is known for its antitumor activities. However, its clinical efficacy is
      limited due to poor bioabsorption. A new class of synthetic analogs of curcumin,
      namely diarylidenylpiperidone (DAP), has been developed with substantially higher
      anticancer activity than curcumin. However, its cellular uptake and bioabsorption
      have not been evaluated. In this study we have determined the absorption of a
      representative DAP compound, HO-3867, using optical and electron paramagnetic
      resonance spectrometry. The cellular uptake of HO-3867 was measured in a variety
      of cancer cell lines. HO-3867 was taken in cells within 15 minutes of exposure
      and its uptake was more than 100-fold higher than curcumin. HO-3867 was also
      retained in cells in an active form for 72 hours and possibly longer. HO-3867 was
      substantially cytotoxic to all the cancer cells tested. However, there was no
      direct correlation between cellular uptake and cytotoxicity suggesting that the
      cytotoxic mechanisms could be cell-type specific. When administered to rats by
      intraperitoneal injection, significantly high levels of HO-3867 were found in the
      liver, kidney, stomach, and blood after 3 hours. Also, significant accumulation
      of HO-3867 was found in murine tumor xenografts with a dose-dependent inhibition
      of tumor growth. The results suggest that the curcumin analog has substantially
      higher bioabsorption when compared to curcumin.

PMID- 20798599
TI  - Movement within and movement beyond: synaptotagmin-mediated vesicle fusion during
      chemotaxis.
AB  - Leukocyte chemotaxis plays an essential role in generating and delivering immune
      responses and is a critical component of inflammation. In order to identify novel
      genes and pathways important for regulating chemotaxis, we performed an RNAi
      based screen and identified several genes involved with vesicle movement and
      fusion as mediators of chemotaxis. Our recently published data show that during
      chemotaxis vesicle trafficking proteins are required for lysosome fusion, uropod
      release and efficient directed cell migration.

PMID- 20798600
TI  - The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations.
AB  - Mitochondrial dysfunction is an early sign of many neurodegenerative diseases.
      Very recently, two Parkinson disease (PD) associated genes, PINK1 and Parkin,
      were shown to mediate the degradation of damaged mitochondria via selective
      autophagy (mitophagy). PINK1 kinase activity is needed for prompt and efficient
      Parkin recruitment to impaired mitochondria. PD-associated Parkin mutations
      interfere with the process of mitophagy at distinct steps. Here we show that
      whole mitochondria are turned over via macroautophagy. Moreover, disease
      associated PINK1 mutations also compromise the selective degradation of
      depolarized mitochondria. This may be due to the decreased physical binding
      activity of PD-linked PINK1 mutations to Parkin. Thus, PINK1 mutations abrogate
      autophagy of impaired mitochondria upstream of Parkin. In addition to compromised
      PINK1 kinase activity, reduced binding of PINK1 to Parkin leads to failure in
      Parkin mitochondrial translocation, resulting in the accumulation of damaged
      mitochondria, which may contribute to disease pathogenesis.

PMID- 20798601
TI  - CanScript, an 18-Base pair DNA sequence, boosts tumor cell-specific promoter
      activity: implications for targeted gene therapy.
AB  - Gene therapy protocols for the treatment of cancer often employ gene promoter
      sequences that are known to be over-expressed in specific tumor cell types
      relative to normal cells. These promoters, while specific, are often weakly
      active. It would be desirable to increase the activity of such promoters, while
      at the same time retain specificity, so that the therapeutic gene is more
      robustly expressed. Using a luciferase reporter DNA construct in both in vitro
      cell transfection assays and in vivo mouse tumor models, we have determined that
      in the absence of any other DNA sequence, a previously identified 18-base pair
      enhancer sequence called CanScript, lying upstream of the MSLN gene, has ~25% of
      the promoter activity of CAG, a very strong non-specific promoter/enhancer, in
      tumor cells in which MSLN is highly expressed. Furthermore, tandem repeat copies
      of CanScript enhance transcription in a dose-dependent manner and, when coupled
      with promoter sequences that are active in tumor cells, increase promoter
      activity. These findings suggest that the incorporation of CanScript into gene
      constructs may have application in enhancing activity of promoters used in cancer
      targeting gene therapy strategies, thereby improving therapeutic efficacy.

PMID- 20798602
TI  - Specific cell ablation in Drosophila using the toxic viral protein M2(H37A).
AB  - The expression of toxic viral proteins for the purpose of eliminating distinct
      populations of cells, while leaving the rest of an organism unaffected, is a
      valuable method for analyzing development. Using the Gal4-UAS system, we employed
      the M2(H37A) toxic ion channel of the influenza-A virus to selectively ablate the
      Drosophila eye-antennal imaginal discs, hemocytes, dorsal vessel and nervous
      tissue, and comparatively monitored the effects of expressing the apoptosis
      promoting protein Reaper in identical cell populations. In this report, we
      demonstrate the effectiveness of M2(H37A)-mediated ablation as a new means to
      selectively eliminate cells of interest during Drosophila development.

PMID- 20798603
TI  - Alteration of wing size through over-expression of scribbler isoforms.
AB  - Scribbler was identified as a genetic modifier of the Drosophila tumor suppressor
      gene Merlin. Loss of Merlin results in hyperplasia in a number of different
      epithelial tissues including the wing and eye imaginal discs, however loss of
      scribbler does not. The lack of an overt proliferation sbb phenotype has
      complicated the mechanistic link between sbb and Merlin. Scribbler encodes two
      novel transcriptional repressors which function in numerous processes including
      axon guidance and pattern formation within the wing. While the two sbb isoforms
      have some redundant functions over-expression of two sbb isoforms within the wing
      show distinct and opposite effects. Over-expression of the smaller SbbA isoform
      results in a larger wing, while over-expression of larger SbbB isoform results in
      a smaller wing with defects in venation. Co-expression of sbb isoforms
      ameliorates the effects of expression of either isoform alone, suggesting that a
      balance between the express of each scribbler isoform is required to ensure
      proper size of the wing.

PMID- 20798604
TI  - Discs large in the Drosophila testis: an old player on a new task.
AB  - Gamete development requires a coordinated soma-germ line interaction that ensures
      renewal and differentiation of germline and somatic stem cells. The physical
      contact between the germline and somatic cell populations is crucial because it
      allows the exchange of diffusible signals among them. The tumor suppressor gene
      discs large (dlg) encodes a septate junction protein with functions in epithelial
      cell polarity, asymmetric neuroblast division and formation of neuromuscular
      junctions. Our recent work reveals a new role of dlg in the Drosophila testis, as
      mutations in dlg lead to testis defects and cell death. Dlg is required
      throughout spermatogenesis in the somatic lineage and its localization changes
      from a uniform distribution along the plasma membrane of somatic cells in the
      testis apex, to a restricted localization on the distally located somatic cell in
      growing cysts. The extensive defects in dlg testis underline the importance of
      the somatic cells in the establishment and maintenance of the male stem cell
      niche and somatic cell differentiation. Here, we discuss our latest findings on
      the role of dlg in the Drosophila testis, supporting the view that junction
      proteins are dynamic structures, which can provide guiding cues to recruit
      scaffold proteins or other signaling molecules.

PMID- 20798605
TI  - Lgl/aPKC and Crb regulate the Salvador/Warts/Hippo pathway.
AB  - A key goal of developmental biology is to understand the mechanisms that
      coordinate organ growth. It has long been recognized that the genes that control
      apico-basal cell polarity also regulate tissue growth. How loss of cell polarity
      contributes to tissue overgrowth has been the subject of much speculation. Do
      loss-of-function mutations in cell polarity regulators result in secondary
      effects that globally deregulate cell proliferation, or do these genes
      specifically control growth pathways? Three recent papers have shown that the
      apico-basal polarity determinants Lgl/aPKC and Crb regulate tissue growth
      independently of their roles in cell polarity and coordinately regulate cell
      proliferation and cell death via the Salvador/Warts/Hippo (SWH) pathway. Lgl/aPKC
      are required for the correct localization of Hippo (Hpo)/Ras associated factor
      (RASSF), while Crb regulates the levels and localization of Expanded (Ex),
      indicating that cell polarity determinants modify SWH pathway activity by
      distinct mechanisms. Here, we review the key data that support these conclusions,
      highlight remaining questions and speculate on the underlying mechanisms by which
      the cell polarity complexes interact with the SWH pathway. Understanding the
      interactions between cell polarity regulators and the SWH pathway will improve
      our knowledge of how epithelial organization and tissue growth are coordinated
      during development and perturbed in disease states such as cancer.

PMID- 20798606
TI  - The control of EGF signaling and cell fate in the Drosophila abdomen.
AB  - How cells integrate both patterning and signaling information to select between
      distinct cell fates is a fundamental problem in developmental biology. In this
      short review, I focus on recent findings of how the Hox and senseless patterning
      genes regulate epidermal growth factor (EGF) signaling and cell fate within the
      Drosophila abdomen. In Li-Kroeger et al., we described how a Hox and Senseless
      transcription factor competition functions as a molecular switch on a cis
      regulatory element in the rhomboid (rho) gene to control EGF signaling within the
      peripheral nervous system (PNS). Here, I discuss an additional implication of
      these findings: that rho contains at least two cis-regulatory elements to control
      EGF secretion from the PNS, each to induce a different cell fate.

PMID- 20798607
TI  - Satellite signaling at synapses.
AB  - Neural function requires effective communication between neurons and their
      targets at synapses. Thus, proper formation, growth and plasticity of synapses
      are critical to behavior. A retrograde (muscle to neuron) BMP signal is required
      to promote synaptic growth, homeostasis and stability at Drosophila neuromuscular
      junctions (NMJs).(1-4) We recently demonstrated that this signal constitutes an
      instructive signal that sculpts synaptic growth in a graded manner and uncovered
      a presynaptic endocytic mechanism that modulates BMP signaling levels. In the
      absence of this regulation, excessive BMP signaling results in overgrown NMJs
      with a proliferation of ectopic boutons.(5).

PMID- 20798608
TI  - Traf6 and A20 differentially regulate TLR4-induced autophagy by affecting the
      ubiquitination of Beclin 1.
AB  - Toll-like receptor 4 (TLR4) signaling triggers autophagy, which has been linked
      to both adaptive and innate immunity. Engagement of TLR4 recruits to the receptor
      complex Beclin 1, a key component of a class III phosphatidylinositol 3-kinase
      complex (PI3KC3) that initiates autophagosome formation. Recently, we found that
      tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6)-mediates
      Lys(63) (K63)- linked ubiquitination of Beclin 1 is crucial for TLR4-triggered
      autophagy in macrophages. We identified two TRAF6-binding motifs in Beclin 1 that
      facilitate the binding of TRAF6 and the ubiquitination of Beclin 1. A lysine
      located in the Bcl-2 homology 3 (BH3) domain of Beclin 1 serves as a major site
      for K63-linked ubiquitination. Opposing TRAF6, the deubiquitinating enzyme A20
      reduces the extent of K63-linked ubiquitination of Beclin 1 and limits the
      induction of autophagy in response to TLR4 signaling. Furthermore, treatment of
      macrophages with either interferongamma or interleukin-1 triggers the K63-linked
      ubiquitination of Beclin 1 and the formation of autophagosomes. These results
      indicate that the status of K63-linked ubiquitination of Beclin 1 plays a key
      role in regulating autophagy during inflammatory responses.

PMID- 20798609
TI  - The role of chromatin condensation during granulopoiesis in the regulation of
      gene cluster expression.
AB  - Changes in nuclear architecture play an important role in the regulation of gene
      expression. The importance of epigenetic changes is observed during
      granulopoiesis, when changes in the nuclear architecture are considered a major
      factor that influences the downregulation of genes. We aimed to assess the
      influence of chromatin condensation on the regulation of gene expression during
      granulopoiesis. Based on a previously published microarray analysis, we chose
      loci with different levels of transcriptional activity during granulopoiesis.
      Fluorescent in situ hybridisation (FISH) and immunofluorescent labelling of RNA
      polymerase II were used to determine the relationship between the transcriptional
      activity of gene clusters and their localisation within areas with different
      levels of chromatin condensation. Although active loci were positioned outside of
      areas of condensed chromatin, downregulation of genes during granulopoiesis was
      not accompanied by a shift of the downregulated loci to condensed areas. Only the
      beta-globin cluster was subjected to chromatin condensation and localised to
      condensed areas. Our results indicate that granulopoiesis is accompanied by a non
      random, tissue-specific pattern of chromatin condensation. Furthermore, we
      observed that the decrease in the quantity of RNA polymerase II correlates with
      the differentiation process and likely acts in synergy with chromatin
      condensation to downregulate total gene expression.

PMID- 20798610
TI  - Anti-neoplastic activity of the cytosolic FoxO1 results from autophagic cell
      death.
AB  - Although Beclin 1 and mTOR are considered to be the main molecules to modulate
      the autophagic process, searching for other autophagy-regulating molecules is
      still an ongoing challenge to scientists. Here we demonstrated that FoxO1, a
      forkhead O family protein, is a mediator of autophagy. Upon oxidative stress or
      serum starvation, endogenous FoxO1 was required for autophagy in human cancer
      cell lines, and this process was independent of FoxO1's transcriptional activity
      as well as mTOR or Beclin 1. In response to stress, FoxO1 dissociated from an
      NAD(+)-dependent histone deacetylase SIRT2 and FoxO1 thus became acetylated and
      in turn bound to Atg7, an E1-like protein, to influence the autophagic process
      leading to cell death. In particular, cytosolic FoxO1 suppressed tumor xenograft
      growth in nude mice in an autophagy-dependent manner. Our studies provide
      evidence that cytosolic FoxO1-induced autophagy is associated with tumor
      suppression function.

PMID- 20798611
TI  - Progranulin mutations are a common cause of FTLD in Northern Italy.

PMID- 20798612
TI  - Pilot trial of memantine in primary progressive aphasia.

PMID- 20798614
TI  - Healthcare reform and nursing: what does it mean?

PMID- 20798613
TI  - Can tetrathiomolybdate be a potential agent against Alzheimer disease? A
      hypothesis based on abnormal copper homeostasis in brain.

PMID- 20798615
TI  - Evaluating the evidence in evidence-based design.
AB  - Evidence-based practice has become a valued process on which to base our clinical
      and facility design decisions, yet not all evidence is created equal. This
      facility design department aims to expand nurse leaders' knowledge and
      competencies in health facility design and enables them to take leadership roles
      in design efforts. This article focuses on the need to critical appraise facility
      design research articles and rate the strength of the evidence using a
      hierarchical model.

PMID- 20798616
TI  - Social networks as embedded complex adaptive systems.
AB  - As systems evolve over time, their natural tendency is to become increasingly
      more complex. Studies in the field of complex systems have generated new
      perspectives on management in social organizations such as hospitals. Much of
      this research appears as a natural extension of the cross-disciplinary field of
      systems theory. This is the 15th in a series of articles applying complex systems
      science to the traditional management concepts of planning, organizing,
      directing, coordinating, and controlling. In this article, the authors discuss
      healthcare social networks as a hierarchy of embedded complex adaptive systems.
      The authors further examine the use of social network analysis tools as a means
      to understand complex communication patterns and reduce medical errors.

PMID- 20798617
TI  - Is it time to pull the plug on 12-hour shifts? Part 3. harm reduction strategies
      if keeping 12-hour shifts.
AB  - This article is part 3 of the series "Pulling the Plug on 12-Hour Shifts." In
      part 1 (March 2010), the authors provided an update on recent evidence that
      challenges the current scheduling paradigm and supports the lack of safety of
      long work hours. Part 2 (April 2010) described the barriers to change and
      challenges for the nurse executive in moving away from the practice of 12-hour
      shifts. This article presents strategies for mitigating the effects of 12-hour
      shifts for nurses who continue to work 12-hour shifts despite the potential risks
      to their health and to patient safety.

PMID- 20798618
TI  - Point-of-care technology supports bedside documentation.
AB  - As the conversion to an electronic health record intensifies, the question of
      which data-entry device works best in what environment and situation is
      paramount. Specifically, what is the best mix of equipment to purchase and
      install on clinical units based on staff preferences and budget constraints? The
      authors discuss their evaluation of stationary personal computers, workshops on
      wheels, and handheld tablets related to timeliness of data entry and their use of
      focus groups to ascertain the pros/cons of data-entry devices and staff
      preferences. An assessment of the implications for costs related to the
      timeliness of data entry is also presented.

PMID- 20798619
TI  - Transforming nursing workflow, part 1: the chaotic nature of nurse activities.
AB  - OBJECTIVE: To quantitatively measure workflow and computer use, the activities of
      27 medical-surgical RNs were recorded through direct observation. BACKGROUND:
      Previous studies have shown how nurses spend their time but have not documented
      the pattern, duration, or frequency of activities. The absence of this
      information is problematic for leaders charged with improving performance and
      staff development. METHODS: Observers recorded nurse activities and location in
      real time using predefined lists. More than 98 hours of observations were
      recorded. RESULTS: Assessment, charting, and communicating were the most frequent
      activities, consuming 18.1%, 9.9%, and 11.8% of nurse time, respectively. The
      duration of 40% of the activities was less than 10 seconds. Timelines revealed
      that nurses constantly switch activities and locations in a seemingly random
      pattern. CONCLUSION: The results indicate that there is little "flow" in nurse
      workflow. The chaotic pace implies that nurses rarely complete an activity before
      switching to another. The opportunity to use critical thinking and engage in
      planning care is severely limited under these circumstances. The implications for
      cognition and role transformation are discussed. Part 2 of this research explores
      the impact of new technology on nurse activities and workflow.

PMID- 20798620
TI  - Effect of morbidity and mortality peer review on nurse accountability and
      ventilator-associated pneumonia rates.
AB  - OBJECTIVE: This program was designed to evaluate the effect of morbidity and
      mortality peer review conferences (MMPRCs) for ventilator-associated pneumonia
      (VAP) on nurse accountability and compliance with evidence-based VAP prevention
      practices. BACKGROUND: Ventilator-associated pneumonia is associated with longer
      average length of stay (ALOS), greater cost, and increased morbidity and
      mortality. Traditionally, passive or punitive methods have been used to reduce
      undesirable outcomes. The MMPRC is not a conventional nursing intervention.
      METHODS: Each MMPRC included case history, relevant hospital course, diagnostic
      comorbidities, and compliance with VAP prevention strategies. The preventability
      of each VAP was determined by RN peers. Ventilator days, VAP bundle compliance,
      VAP incidence, ICU ALOS, cost, and satisfaction data were collected. RESULTS:
      Nurse accountability improved significantly (chi(2)= 24.041, P < .001), and VAP
      incidence was reduced. Data demonstrated satisfaction with the MMPRC. Number of
      ventilator days and ALOS did not change significantly, although VAP bundle
      compliance improved from 90.1% to 95.2%. CONCLUSIONS: The nonpunitive MMPRC
      process was cost-effective and should be considered for other nurse-sensitive
      indicators to increase nurse accountability and improve outcomes.

PMID- 20798621
TI  - Fall initiatives: redesigning best practice.
AB  - One of the largest categories of reported adverse events in hospitals are patient
      falls, which are estimated to cost more than $20 billion a year. With the goal of
      preventing falls and reducing the seriousness of injuries from falls, a quality
      improvement project was initiated. The authors discuss the project that resulted
      in a best practice toolkit related to decreasing fall-related injuries.

PMID- 20798622
TI  - A curriculum designed to decrease barriers related to scholarly writing by staff
      nurses.
AB  - Demonstrating professional development outcomes, such as scholarly publication,
      is critical as nurse leaders guide organizations seeking recognition as centers
      of excellence. However, personal and situational barriers often prevent staff
      nurses from achieving scholarly publication. This project tested a workshop and
      mentoring approach to decrease publication barriers with staff nurses in 2
      community hospitals. Self-efficacy principles guided the curriculum that resulted
      in a statistically significant improvement in staff nurse perception of
      successful scholarly publication endeavors.

PMID- 20798623
TI  - Surgical strategies to salvage the venous compromised deep inferior epigastric
      perforator flap.
AB  - BACKGROUND: Elevation of the deep inferior epigastric perforator (DIEP) flap
      interrupts its superficial venous system, and if drainage through the deep venous
      system is inadequate the flap may develop congestion. The purpose of this
      retrospective study was to determine the fate of the congested DIEP flap and to
      optimize the strategy for its salvage. METHODS: Thirty-two of 162 patients who
      underwent unilateral breast reconstruction with a DIEP flap developed venous
      congestion. For the purpose of outcome analysis, cases were retrospectively
      allocated to "observation-only" (group A, n = 11), postoperative salvage (group
      B, n = 7), and intraoperative salvage (group C, n = 14), and complications among
      the various groups were compared to determine the necessity and optimal timing of
      salvage intervention. RESULTS: Two flaps (1 in group A, another in group B)
      failed completely, giving a success rate 98.8%. The complication rate and
      hospital stay were significantly lower in group C than in group B (P = 0.03, P =
      0.02). The rate of venous congestion requiring salvage procedures was 13%, with a
      salvage rate of 95%. Salvage procedures included venous augmentation with an
      additional recipient vein in 7 procedures, adding superficial inferior epigastric
      vein (SIEV) to DIEV in 11 procedures, and substituting with SIEV in 7 procedures.
      There was no statistical difference in flap salvage rate using the SIEV between
      "augmentation" and "substitution." CONCLUSIONS: The salvage procedures for venous
      compromised DIEP flap are better performed intraoperatively rather than
      postoperatively to prevent further complications. The engorged SIEV could be
      incorporated by anastomosing to an additional recipient vein or adding to the
      DIEV-internal mammary vein axis or substituting for DIEV.

PMID- 20798624
TI  - Interval inset of TRAM flaps in immediate breast reconstruction: a technical
      refinement.
AB  - PURPOSE: Healthy, viable mastectomy skin is a critical factor in the outcome of
      immediate breast reconstruction. Unfortunately, mastectomy skin viability can be
      problematic and intraoperative assessment is unreliable. For this reason, we have
      modified our approach to immediate transverse rectus abdominus myocutaneous flap
      (TRAM) reconstruction. Instead of completing the reconstruction with a definitive
      inset at the time of the mastectomy, the TRAM flap is left intact and buried
      beneath the mastectomy skin for 3 to 5 days. This falls within the normal period
      of postoperative hospitalization, and at this point, the viability of the
      mastectomy skin is clear. Ischemic skin is debrided and replaced with healthy
      TRAM skin, and nipple reconstruction can be performed at the time of this
      interval inset. The purpose of this study was to review a large case series of
      patients who underwent an interval inset of their TRAM flap in the setting of
      immediate skin-sparing mastectomy. METHODS: Retrospective chart data were
      obtained for all TRAM patients who underwent immediate postmastectomy breast
      reconstruction by a single surgeon during a 5-year period. Data were collected on
      procedures, complications, margin status, and number of immediate versus delayed
      nipple reconstructions. RESULTS: There were 63 patients who underwent immediate
      TRAM reconstruction with interval inset of the flap. This included 25 bilateral
      cases, for a total of 89 flaps. Interval insets were performed an average of 3.9
      days after the TRAM. Twenty-seven percent (17/63) required replacement of
      nonviable mastectomy skin with TRAM skin and had no nipple reconstruction; 4.8%
      (3/63) had additional skin taken because of residual tumor close to or at the
      mastectomy margins. Seventy-three percent of patients (46/63) had a nipple
      reconstruction with minimal or no mastectomy skin loss. CONCLUSION: We present
      the interval inset of TRAM flaps during the normal period of postoperative
      hospitalization as a technical refinement to optimize cosmetic outcomes.
      Mastectomy skin viability can be more easily assessed and necrotic or ischemic
      skin replaced with TRAM skin as needed. This avoids the need for prolonged
      dressing changes or a compromised aesthetic result from skin loss. When there is
      no major skin loss, the nipple reconstruction can be performed concurrently with
      the inset. These refinements optimize the appearance of the reconstructed breast
      and reduce the need for future surgeries. In addition, the surgical oncologist
      has the opportunity to excise close or positive margins as indicated by
      pathologic findings. Thus, the benefits of the interval inset of TRAM flaps are
      shared by the reconstructive surgeon, the surgical oncologist, and most
      importantly, the patient.

PMID- 20798625
TI  - A study on repair of porcine articular cartilage defects with tissue-engineered
      cartilage constructed in vivo by composite scaffold materials.
AB  - The study was performed to find out a promising injectable composite scaffold for
      cartilage tissue engineering. By using a composite of allogenous cartilage
      microparticle acellular tissue matrix (CMACTM) and fibrin glue (Fg) as injectable
      scaffold materials, tissue-engineered cartilage was constructed in vivo, and the
      effects of which on the repair of porcine articular cartilage defects were
      observed. CMACTM was obtained from domestic pigs. The chondrocytes were prepared
      from experimental mini-type pigs and expanded in vitro. Fg was used as a scaffold
      material. The composite of CMACTM, second-passage chondrocytes, and Fg was
      replanted to the articular cartilage defective regions in autologous mini-type
      pig by injection. At 12 weeks after replantation, samples were collected and
      analyzed by general observation and histologic staining.The constructed tissue
      engineered cartilage exhibited a good efficiency in the repair of articular
      cartilage defects. Cells in the constructed tissue-engineered cartilage grew well
      and were able to secrete cartilaginous matrix. The tissue-engineered cartilage
      showed a better biologic performance than the control. A composite of allogenous
      CMACTM and Fg was a promising injectable scaffold for cartilage tissue
      engineering, which could be used to repair articular cartilage defects by a
      minimally invasive procedure.

PMID- 20798626
TI  - Symptomatic congenital pisiform hamate coalition.
AB  - Congenital fusions of the carpal bones are rare anomalies, which occur in less
      than 1% of the population. This article describes a congenital pisiform hamate
      coalition which became symptomatic when caused by a trauma. The condition was
      successfully treated with the resection of the synchondrosis, autogenous bone
      graft, and screw stabilization.

PMID- 20798627
TI  - Suprathel-acetic acid matrix versus acticoat and aquacel as an antiseptic
      dressing: an in vitro study.
AB  - BACKGROUND: The treatment of burn wounds is still a challenge regarding the
      management of antiseptic wound conditioning. Especially, in the United States,
      silver-containing dressings, such as Acticoat and Aquacel are frequently used.
      Because silver-containing dressings have well-known drawbacks such as an
      antimicrobial lack against Pseudomonas aeruginosa, we sought to develop an
      alternative dressing method. In previous studies, we could demonstrate the
      excellent antiseptic properties of acetic acid against common burn unit germs,
      and in another study, the feasibility and suitability of a Suprathel-acetic acid
      matrix as an antiseptic dressing. MATERIALS AND METHODS: This study was designed
      to test the in vitro antimicrobial effect of a Suprathel-acetic acid matrix
      versus Acticoat and Aquacel. To cover the typical bacterial spectrum of a burn
      unit, the following Gram-negative and Gram-positive bacteria strains were tested:
      Escherichia coli, extended-spectrum beta-lactamase-positive Klebsiella
      pneumoniae, P. aeruginosa, Acinetobacter baumannii, Enterococcus faecalis, and
      methicillin-resistant Staphylococcus aureus. RESULTS: The tests showed an
      excellent bactericidal effect of the Suprathel-acetic acid matrix particularly
      with problematic Gram-negative bacteria such as Proteus vulgaris, P. aeruginosa,
      and Acinetobacter baumannii. The efficiency was superior to that of Acicoat and
      Aquacel. CONCLUSIONS: Our results support the notion, that the Suprathel-acetic
      acid matrix has an excellent bactericidal effect and therefore seems to be
      suitable as a local antiseptic agent in the treatment of burn wounds.

PMID- 20798628
TI  - Biomechanical properties of a new multilocking loop peripheral suture technique
      for the repair of flexor tendons: a comparative experimental study.
AB  - We aimed to evaluate the biomechanical properties of a new multilocking loop
      peripheral suture technique. For this aim, 40-deep digital flexor tendons of
      adult male sheep front limb were divided and then repaired using one of the
      following methods: simple peripheral suture plus 2- or 4-strand Kessler core
      suture or a new multilocking loop peripheral suture combined with either 2- or 4
      strand Kessler core suture. Intact tendons were used as controls. The following
      biomechanical parameters were tested: ultimate tensile strength, energy to
      failure, 2-mm gap formation force, stiffness, and mechanism of failure.
      Regardless of the number of core suture strands, the new technique resulted in
      greater ultimate tensile strength, energy to failure, 2-mm gap formation force,
      and stiffness values, compared with simple running peripheral suture. In
      conclusion, the new multilocking loop peripheral suture technique represents a
      biomechanically strong and technically suitable method for flexor tendon repair.

PMID- 20798629
TI  - The relationship between the thickness of de-epithelialization and occurrence of
      sebaceous cysts at the incision site after mastopexy and reduction mammaplasty.
AB  - Periareolar sebaceous cysts at the incision site after mastopexy and reduction
      mammaplasty are very unpleasant complications that affect the surgical result and
      the degree of patient satisfaction. The author sought to investigate the cause
      and prevention of such sebaceous cysts. Sixty patients undergoing mastopexy or
      reduction mammaplasty were randomly divided into 2 groups. Periareolar de
      epithelialization was performed to a depth of superficial layer of the dermis in
      group A and nearly the full thickness of the dermis in group B, and the incidence
      of sebaceous cysts was compared between these 2 groups. Patients were followed-up
      for 2 to 4 years. In group A, sebaceous cysts at the incision site were found in
      4 patients (13.3%); however, no sebaceous cysts occurred in group B. Increasing
      the thickness of de-epithelialization appears to decrease the incidence of
      sebaceous cysts at the incision site.

PMID- 20798630
TI  - The PreFACE: A preoperative psychosocial screen for elective facial cosmetic
      surgery and cosmetic dentistry patients.
AB  - BACKGROUND: Currently no brief and objective screening protocol exists to assist
      surgeons and dentists in the identification of patients who are likely to report
      unsatisfactory outcomes after cosmetic surgery interventions. The aims of this
      study were to (1) investigate the relationship between postoperative
      dissatisfaction and preoperative characteristics (psychiatric disturbance,
      anxiety, depression, self-esteem, dysmorphic concern, and body image), and (2)
      empirically derive a preoperative psychosocial screening instrument to identify
      patients who may require preoperative assessment or counseling. METHODS: The
      sample composed of 84 patients (69 women and 15 men) undergoing elective cosmetic
      facial surgery or cosmetic dentistry. Before surgery, a self-report questionnaire
      was administered to the patients, which comprised questions designed to evaluate
      many of the psychosocial characteristics thought to be associated with
      unsatisfactory outcomes. Six months after surgery, a questionnaire was
      administered to the patients, which included items evaluating postoperative
      satisfaction. RESULTS: The findings revealed that preoperative psychiatric
      disturbance, anxiety, depression, low appearance evaluation, and body areas
      dissatisfaction are psychosocial risk factors that indicate an increased
      likelihood of patient dissatisfaction with surgical outcomes. The PreFACE
      (Preoperative FAcial Cosmetic surgery Evaluation), a brief objective preoperative
      screening questionnaire that can be easily and efficiently administered to
      elective facial cosmetic surgery and cosmetic dentistry patients, was empirically
      derived. It is able to identify most patients who are likely to express
      dissatisfaction and minimizes the selection of those who will express
      satisfaction. The PreFACE is recommended for validation using other cosmetic
      surgery populations. CONCLUSIONS: The routine use of PreFACE is recommended for
      identification of patients who may benefit from preoperative counseling.

PMID- 20798631
TI  - Lash ptosis and associated factors in Asians.
AB  - Lash ptosis (LP) is one of the important factors to be considered in
      blepharoplasty or correction of ptosis, but LP is an often overlooked symptom. We
      evaluate normal variations in the degree of LP to analyze the relationship
      between LP and its associated factors in Asians. One-hundred and sixty patients
      without ptosis and 16 patients with acquired ptosis were included in this study.
      We measured the degree of LP, marginal reflex distance 1, levator function, and
      presence or absence of a double fold. A significant difference was observed in LP
      rating between the nonptosis and acquired ptosis groups (P = 0.00), along with a
      significant correlation between LP rating and marginal reflex distance 1 (r = 
      0.272, P < 0.01), levator function (r = -0.170, P < 0.01), and absence or
      presence of double fold (r = -0.233, P < 0.01). Our results may be beneficial in
      the design of a basic plan for Asian patients with LP at the time of upper eyelid
      surgery, such as blepharoplasty or correction of ptosis.

PMID- 20798632
TI  - A treatment strategy for postburn neck reconstruction: emphasizing the functional
      and aesthetic importance of the cervicomental angle.
AB  - The authors describe an algorithm for reconstruction of both the soft tissue and
      skeletal components of severe postburn neck deformities. The critical functional
      and aesthetic importance of the cervicomental angle is emphasized. The neck is
      subdivided into 3 anatomic subunits: (1) lower lip/chin subunit, (2) submental
      subunit, and (3) anterior neck subunit. After release of contractures,
      platysmaplasty is performed to prevent recurrence and to deepen the cervicomental
      angle. In cases where chin retrusion is present, sliding genioplasty is
      performed. The 3 subunits are resurfaced individually by skin grafts and free
      flaps. The combined scapular and parascapular bilobed free flap is an ideal flap
      for cases involving 2 subunits. Fifty patients with severe postburns neck
      contractures were treated. After excision and release of scar, 47 (94%) patients
      underwent platysmaplasty, and 12 (24%) patients underwent sliding genioplasty.
      Defects were covered with skin grafts alone in 20 (40%) patients, with free flaps
      only in 22 (44%) patients, and with a combination of skin grafts and free flaps
      in 8 (16%) patients.

PMID- 20798633
TI  - The effect of centrifugal forces on viability of adipocytes in centrifuged
      lipoaspirates.
AB  - Standard protocols for autologous fat transfer involve centrifugation of the
      lipoaspirate for better separation. The effect of the centrifugal forces on cell
      viability and possible induction of apoptosis is discussed controversially in
      current literature. We have examined the vitality of adipocytes in lipoaspirates
      after centrifugation by 8 different accelerations up to 20.000g immediately after
      the respective centrifugation as well as 4 days later by staining. No significant
      alterations in the viability of differently centrifuged adipocytes were found.
      Cultivation of the samples after centrifugation revealed no apoptotic changes.
      Our results show that centrifugation, as a part of the protocol of lipofilling,
      has no effect on the survival rate of isolated adipocytes in the purified fat. In
      contrast, lipoaspirates centrifuged with higher accelerations seem to be better
      cleansed of oil and cell debris than samples treated with lower centrifugal
      forces.

PMID- 20798634
TI  - Transversus abdominis plane block reduces the analgesic requirements after
      abdominoplasty with flank liposuction.
AB  - INTRODUCTION: The transversus abdominis plane (TAP) block is a technique of
      locoregional anesthesia that blocks the sensorial afferent nerves localized
      between the transversus abdominis muscle and the internal oblique muscle. We
      describe results obtained with a case control study between patients undergoing
      abdominoplasty with the TAP block compared with a similar group of patients not
      receiving the block. MATERIALS AND METHODS: Medical notes were reviewed, and
      patients were classified according to the presence of TAP. Outcomes evaluated
      were the requirements of morphine in the first postoperative hour and the number
      of co-codamol tablets administered afterward. RESULTS: Seventy-five patients were
      screened. No intra- or postoperative complications were recorded. TAP+ patients
      required significantly less analgesia during the first 12 postoperative hours (P
      < 0.001). The patients with increased body mass index and large flap resected
      were more likely to fail the anesthetic block and required postoperative
      analgesia. CONCLUSIONS: In aesthetic abdominal surgery, the TAP block is safe, is
      performed without ultrasound guidance, and markedly reduces the requirement of
      postoperative opioid analgesia. Future studies will now confirm these results and
      evaluate the consequences in terms of postoperative nausea, vomiting, and overall
      satisfaction of patients.

PMID- 20798635
TI  - Parental autoimmune diseases associated with autism spectrum disorders in
      offspring.
AB  - BACKGROUND: Autism spectrum disorders are often idiopathic. Studies have
      suggested associations between immune response and these disorders. We explored
      associations between parental autoimmune disorders and children's diagnosis of
      autism by linking Swedish registries. METHODS: Data for each participant were
      linked across 3 Swedish registries. The study includes 1227 cases and 25 matched
      controls for each case (30,693 controls with parental linkage). Parental
      diagnoses comprised 19 autoimmune disorders. We estimated odds ratios (ORs) using
      multivariable conditional logistic regression. RESULTS: Parental autoimmune
      disorder was weakly associated with autism spectrum disorders in offspring
      (maternal OR = 1.6 [95% confidence interval = 1.1-2.2]; paternal OR = 1.4 [1.0
      2.0]). Several maternal autoimmune diseases were correlated with autism. For both
      parents, rheumatic fever was associated with autism spectrum disorders.
      CONCLUSIONS: These data support previously reported associations between parental
      autoimmune disorders and autism spectrum disorders. Parental autoimmune disorders
      may represent a critical pathway that warrants more detailed investigation.

PMID- 20798636
TI  - Birth weight and adult hypercholesterolemia: subgroups of small-for-gestational
      age based on maternal smoking status during pregnancy.
AB  - BACKGROUND: Being born small-for-gestational-age (SGA) is associated with
      hypercholesterolemia in later life. It is possible that only certain subgroups of
      SGA are at elevated risk for hypercholesterolemia. We examined the associations
      between SGA subgroups based on levels of maternal smoking during pregnancy and
      adult hypercholesterolemia. METHODS: A subsample of 1625 adult offspring from the
      Collaborative Perinatal Project were followed at mean age 39 years. Subjects were
      classified by recorded fetal growth and maternal smoking status during pregnancy.
      Clinical diagnosis of hypercholesterolemia was obtained in interviews. RESULTS:
      Compared with the appropriate-for-gestational-age subgroup without maternal
      smoking during pregnancy, only SGA subgroups with maternal smoking during
      pregnancy had higher risk of hypercholesterolemia: for heavy smoking, adjusted
      hazard ratio = 2.5 (95% confidence interval = 1.4-4.3); moderate smoking, 1.7
      (1.0-2.8); nonsmoking, 1.1 (0.5-2.1). CONCLUSION: Only SGA infants whose mothers
      smoked during pregnancy had elevated risk of hypercholesterolemia in adulthood.

PMID- 20798637
TI  - Associations between serum lipid levels and chronic low back pain.
AB  - BACKGROUND: Low back pain may be related to abnormal lipid levels because of
      atherosclerosis in arteries supplying the lumbar region. METHODS: In the cross
      sectional HUNT 2 study in the Norwegian county of Nord-Trondelag, lipid levels
      were measured in 33,962 women and 30,031 men. A total of 8954 women (26%) and
      6273 men (21%) reported suffering from low back pain continuously for at least 3
      months in the past year. RESULTS: In age-adjusted analyses, the prevalence of low
      back pain was inversely associated with HDL cholesterol and positively associated
      with triglycerides, with stronger associations in women than in men. Relatively
      weak associations remained in women after adjustment for smoking, physical
      activity, education, work status, blood pressure, and body mass, but no
      associations remained among men. Total cholesterol levels were unrelated to low
      back pain in either sex after age adjustment. CONCLUSIONS: The results are partly
      consistent with the atherosclerosis hypothesis.

PMID- 20798638
TI  - HIV treatment as prevention: to be or not to be?

PMID- 20798639
TI  - The application of Aronson's taxonomy to medication errors in nursing.
AB  - Medication administration is a frequent nursing activity that is prone to error.
      In this study of 318 self-reported medication incidents (including near misses),
      very few resulted in patient harm-7% required intervention or prolonged
      hospitalization or caused temporary harm. Aronson's classification system
      provided an excellent framework for analysis of the incidents with a close
      connection between the type of error and the change strategy to minimize
      medication incidents. Taking a behavioral approach to medication error
      classification has provided helpful strategies for nurses such as nurse-call
      cards on patient lockers when patients are absent and checking of medication sign
      off by outgoing and incoming staff at handover.

PMID- 20798640
TI  - Barriers to implementation of workplace health interventions: an economic
      perspective.
AB  - OBJECTIVE: To identify insurance related, structural, and workplace cultural
      barriers to the implementation of effective preventive and upstream clinical
      interventions in the working age adult population. METHODS: Analysis of avoided
      costs from perspective of health economics theory and from empiric observations
      from large studies; presentation of data from our own cost-plus model on
      integrating health promotion and ergonomics. RESULTS: We identify key avoided
      costs issues as a misalignment of interests between employers, insurers, service
      institutions, and government. Conceptual limitations of neoclassical economics
      are attributable to work culture and supply-driven nature of health care.
      DISCUSSION: Effective valuation of avoided costs is a necessary condition for
      redirecting allocations and incentives. Key content for valuation models is
      discussed.

PMID- 20798641
TI  - Accidental hazardous material releases with human impacts in the United States:
      exploration of geographical distribution and temporal trends.
AB  - OBJECTIVE: To investigate the circumstances and geographic and temporal
      distributions of hazardous material releases and resulting human impacts in the
      United States. METHOD: Releases with fatalities, injuries, and evacuations were
      identified from reports to the National Response Center between 1990 and 2008,
      correcting for data quality issues identified in previous studies. RESULTS: From
      more than 550,000 reports, 861 deaths, 16,348 injuries and 741,427 evacuations
      were identified. Injuries from releases of chemicals at fixed facilities and
      natural gas from pipelines have decreased whereas evacuations from petroleum
      releases at fixed facilities have increased. CONCLUSION: Results confirm recent
      advances in chemical and pipeline safety and suggest directions for further
      improvement including targeted training and inspections and adoption of
      inherently safer design principles.

PMID- 20798642
TI  - The impact of precancerous cervical lesions on functioning at work and work
      productivity.
AB  - OBJECTIVE: To assess the work performance and productivity impact of human
      papillomavirus (HPV). METHODS: A cross-sectional study compared 94 employed women
      with clinically significant HPV-related cervical lesions with 118 healthy
      controls. Data were collected by self-administered web-based questionnaire. At
      work performance limitations and productivity loss (presenteeism) and absenteeism
      were measured. Univariate and multivariate case-control group and clinical
      subgroup differences were tested. RESULTS: Based on adjusted mean scores, the HPV
      group had significantly more at-work limitations and productivity loss than
      controls (P = 0.009), higher absence rates (P = 0.002), and significantly more
      productivity loss because of absences (P = 0.007). At-work limitations varied in
      association with martial status (P = 0.025); at-work productivity loss was
      associated with years of education (P = 0.039). CONCLUSIONS: HPV is costly for
      working women, their employers, and the economy.

PMID- 20798643
TI  - Sickness absence, employment history, and high-risk employees: a 10-year
      longitudinal study.
AB  - OBJECTIVE: To investigate the impact of employment characteristics on the
      occurrence of long-term sickness absence taking socioeconomic covariates into
      account. METHODS: A longitudinal analysis was conducted for 62,745 employees aged
      18 to 64 during 1990-1999. A nonlinear random-effects model was used. In
      particular, the missing data patterns and their relationship with sickness
      absence were studied. RESULTS: Strong relationship of socioeconomic background
      with occurrence of long-term sickness absence (>= 3 days) was found. The missing
      data patterns significantly predicted sickness absence for female employees. In
      subsequent analysis, the discontinuous employment history with high occurrence of
      short-term sickness absence (<3 days) appeared to be strongly linked to long-term
      sickness absence in young women. CONCLUSIONS: An investigation of missing values
      and short-term sickness absence as predictors for long-term sickness absence
      uncovered that young women with irregular employment history constituted high
      risk employees.

PMID- 20798644
TI  - Internal exposure, effect monitoring, and lung function in welders after acute
      short-term exposure to welding fumes from different welding processes.
AB  - OBJECTIVE: In this study, the effect of short-term exposure to welding fumes
      emitted by different welding techniques on workers was investigated. METHODS: In
      a 3-fold crossover study, six welders used three different welding techniques for
      3 hours. Before and after welding, blood and urine samples were collected to
      perform biomonitoring of metals. Breath condensate was collected to assess
      inflammatory reactions, and lung function measurements were performed. RESULTS:
      Welding led to a significant increase of chromium and nickel in blood and urine
      and of nitrate and nitrite in exhaled breath condensate. These increases were
      higher for manual metal arc welding with alloyed material (MAW-a). Several lung
      function parameters decreased after welding. This decrease was significantly
      higher after MAW-a. CONCLUSIONS: In respect to biological effects, MAW-a seems to
      be more important than other welding techniques.

PMID- 20798645
TI  - Back injury trajectories in heavy industries: defining outcomes for
      epidemiological research.
AB  - OBJECTIVE: To propose an incidence definition of back injury for epidemiologic
      studies using health care contacts. METHODS: Medical services, hospitalizations,
      and workers' compensation data were linked for a longitudinal database of health
      care contacts among a cohort of heavy-industry workers for trajectory, group
      based analysis. RESULTS: During follow-up, 25.8% of workers had no health care
      contacts for back injury. Among workers with at least one contact, four
      trajectories were identified: one with a high probability of back injury during
      follow-up and three with episodic trajectories of increasing and decreasing
      probability of back injury. CONCLUSIONS: Workers with no back injury history
      could be followed for incidence in cohort studies or as controls in case-control
      designs. Episodic groups could be followed for new episodes, providing they were
      free of health care contacts for back injury for at least 3 years.

PMID- 20798646
TI  - Assessment of a Worksite Health Promotion Readiness Checklist.
AB  - OBJECTIVE: To assess the utility of a Worksite Health Promotion Readiness
      Checklist (WRCL) designed to evaluate the worksite's readiness for implementing
      health promotion and health protection programs. METHODS: The WRCL was pilot
      tested in worksites with (WHPy) and without (WHPn) health promotion programs. The
      two parts of WRCL scores (observational and administrative) for WHPy and WHPn
      sites were compared within and between the worksites to establish WRCL utility
      and sensitivity. RESULTS: Observational WRCL (completed by two observers per
      site) demonstrated high interrater reliability (P < 0.05) for most items.
      Administrative WRCL (completed by three administrators per site) showed some
      discrepant responses between administrators. Overall, both sections of WRCL
      produced higher scores for WHPy sites. CONCLUSIONS: WRCL could be a valid and
      reliable instrument to measure readiness of a worksite toward health promotion
      and health protection programs.

PMID- 20798647
TI  - Relationship of early magnetic resonance imaging for work-related acute low back
      pain with disability and medical utilization outcomes.
AB  - OBJECTIVE: To examine early magnetic resonance imaging (MRI) utilization for
      workers compensation cases with acute, disabling low back pain and further, to
      examine low or high propensity to undergo early MRI with disability duration,
      medical costs, and surgery. METHODS: Two-year follow-up of 3264 cases. Cox
      regression and generalized linear models were used to examine the association
      between both early MRI (first 30 days postonset) and propensity of belonging to
      the early MRI group (estimated by demographic and severity indicators) with
      outcomes. RESULTS: A total of 21.7% cases had early MRI. After controlling for
      covariates, cases that had early MRI and simultaneously had a low propensity to
      undergo early MRI were more likely to have worse outcomes. CONCLUSIONS: The
      majority of cases had no early MRI indications. Results suggest that iatrogenic
      effects of early MRI are worse disability and increased medical costs and
      surgery, unrelated to severity.

PMID- 20798648
TI  - Formaldehyde and leukemia: an updated meta-analysis and evaluation of bias.
AB  - OBJECTIVE: Formaldehyde exposures are common, and data linking these exposures to
      leukemia have been mixed and controversial. The objective of this analysis is to
      review the current epidemiologic literature on formaldehyde and leukemia.
      METHODS: We performed an updated meta-analysis focusing on high-exposure groups
      and myeloid leukemia and included two large recent studies: one involving >25,000
      workers in US formaldehyde industries and the other involving a cohort of >13,000
      funeral directors and embalmers. RESULTS: Formaldehyde was associated with
      increased risks of leukemia (relative risk = 1.53; 95% confidence interval = 1.11
      to 2.21; P = 0.005; 14 studies), specifically myeloid leukemia (relative risk =
      2.47; 95% confidence interval = 1.42 to 4.27; P = 0.001; 4 studies). CONCLUSION:
      These findings provide evidence of increased myeloid leukemia risk with exposure
      to formaldehyde.

PMID- 20798649
TI  - How do physical activity, sports, and dietary restraint relate to overweight
      associated absenteeism?
AB  - OBJECTIVE: To examine the possible effects of physical activity, sports, and
      restrained eating on the relationship between overweight and absenteeism.
      METHODS: Using a web-based lifestyle questionnaire, responses were obtained from
      3030 employees in a large banking corporation. These data were then coupled with
      data from the company's absenteeism register. RESULTS: Physical activity and
      sports acted as moderator variables in that they both attenuated the positive
      relationship between overweight and/or obesity and absenteeism. Restrained eating
      also moderated the relationship between overweight and absenteeism. Remarkably,
      the degree of overweight was more strongly related to augmented absenteeism in
      people with higher levels of restrained eating. CONCLUSION: To reduce absenteeism
      in overweight employees, it may be beneficial to focus on stimulating physical
      activity and not on interventions aimed at promoting dieting (restrained eating).

PMID- 20798650
TI  - Productivity and health: best practices for better measures of productivity.
AB  - OBJECTIVE: Interest in quantifying the relationship between health status and
      lost productivity has accelerated among employers, researchers, and benefits
      advisors. Our objective was to engage a dialogue to highlight important
      productivity measurement issues for consideration in an overall business
      strategy. METHODS: Critical review of selected topical literature. RESULTS: Four
      functions of productivity measurement are described: 1) the purposes of a
      measurement initiative, 2) norms and benchmarking, 3) health and productivity
      cost estimators, and 4) reporting results. Each function is described in detail;
      challenges are noted; examples are provided. CONCLUSIONS: This article supports
      the Integrated Benefits Institute consensus statements on productivity,
      underscoring the need to develop a conceptual framework of productivity
      measurement that guides the maturation of instruments and sets forth
      recommendations for their application consistent with the descriptive,
      comparative, and evaluative functions that foster health, well-being, and work
      performance.

PMID- 20798651
TI  - Work productivity among employed Canadians with arthritis.
AB  - OBJECTIVE: To compare work productivity among employed people with arthritis to
      healthy controls. METHODS: The data source was the 2005 Canadian Community Health
      Survey. The outcomes were work absence (absenteeism) in the last week and
      reducing activities at work (presenteeism). The key explanatory variable was
      chronic condition status: 1) no chronic conditions; 2) arthritis only; 3) any
      chronic condition but arthritis; and 4) arthritis with other chronic conditions.
      Logistic regressions were used to measure the association between chronic
      conditions status and absenteeism and presenteeism. RESULTS: The odds of
      presenteeism among people with arthritis only were 8-fold greater than the odds
      among people without any chronic conditions. However, arthritis only was not
      found to increase the odds of absenteeism. CONCLUSIONS: Employed people with
      arthritis are able to continue working but at reduced capacity.

PMID- 20798652
TI  - Development of an interactive model of the burden of future coronary heart
      disease from an employer perspective.
AB  - OBJECTIVE: To create a computer-based model for employers to better understand
      the burden of coronary heart disease (CHD) to their organizations. METHODS: A
      user-friendly model was developed to allow employers to evaluate the burden of
      CHD. Inputs include the demographic distribution by age and sex, prevalence of
      CHD and CHD risk factors, direct and indirect medical costs of CHD events, and
      discount and inflation rates. The model contains prediction equations derived
      from National Health and Nutrition Examination Survey data and Framingham Heart
      Study equations, used with employer inputs to predict future CHD events and
      expenditures. RESULTS: Interactive graphs are presented for the employer's
      covered population alongside regional benchmarks. The time horizon and population
      may be adjusted. CONCLUSIONS: This interactive model illustrates how pragmatic
      outcomes research can be converted into a transparent model addressing health
      care budget issues that is readily understood by corporate managers.

PMID- 20798653
TI  - Respiratory muscles, exercise performance, and health in overweight and obese
      subjects.
AB  - PURPOSE: Overweight and obese subjects often perceive increased breathlessness
      during minor exertion and therefore avoid exercise. Respiratory muscle endurance
      training (RMET) can reduce the perception of breathlessness. We hypothesized that
      RMET 1 month before and during a 6-month (3 months supervised + 3 months
      unsupervised) exercise and nutrition counseling program (EN) would improve the
      benefits of EN. METHODS: Twenty-six overweight and obese subjects with
      significant perception of breathlessness during exercise (age = 33 +/- 9 yr, body
      mass index (BMI) = 31.3 +/- 4.9 kg.m(-2)) were randomized to RMET+EN (R+EN) or EN
      alone. R+EN performed 30 min of normocapnic hyperpnea 5 wk(-1) before and 2 wk(
      1) during EN. EN consisted of two strength and three endurance training sessions
      per week, as well as prescribed nutritional composition and a 2.1-kJ (500-kcal)
      energy deficit per day. Both groups had an equal number of laboratory visits
      during the 7 months. Before and after 4 and 7 months, subjects performed a 12-min
      time trial (TT; 6 + 6 min, 2-min pause) and an incremental cycling test (ICT) to
      exhaustion, and blood lipids were assessed. RESULTS: Weight loss was significant
      and similar in both groups (-4.2 vs -3.7 kg; both P < 0.05). During the first 4
      months, distance covered in 12 min improved more (P < 0.05) with R+EN (1678 vs
      1824 m; P < 0.001) than with EN alone (1638 vs 1698 m; P < 0.05), whereas after
      R+EN, breathlessness during the ICT was reduced. Blood lipids of the pooled group
      improved in those subjects with pathologic values before the study. Despite
      reduced training compliance during the unsupervised period, subjects of both
      groups maintained the benefits attained during the supervised period.
      CONCLUSIONS: R+EN improved TT performance more than EN alone, despite similar
      weight loss, possibly owing to the reduced perception of breathlessness.

PMID- 20798655
TI  - Acute calcium ingestion attenuates exercise-induced disruption of calcium
      homeostasis.
AB  - PURPOSE: Exercise is associated with a decrease in bone mineral density under
      certain conditions. One potential mechanism is increased bone resorption due to
      an exercise-induced increase in parathyroid hormone (PTH), possibly triggered by
      dermal calcium loss. The purpose of this investigation was to determine whether
      calcium supplementation either before or during exercise attenuates exercise
      induced increases in PTH and C-terminal telopeptide of Type I collagen (CTX; a
      marker of bone resorption). METHODS: Male endurance athletes (n = 20) completed
      three 35-km cycling time trials under differing calcium supplementation
      conditions: 1) 1000 mg of calcium 20 min before exercise and placebo during, 2)
      placebo before and 250 mg of calcium every 15 min during exercise (1000 mg
      total), or 3) placebo before and during exercise. Calcium was delivered in a 1000
      mg.L(-1) solution. Supplementation was double-blinded, and trials were performed
      in random order. PTH, CTX, bone-specific alkaline phosphatase (BAP; a marker of
      bone formation), and ionized calcium (iCa) were measured before and immediately
      after exercise. RESULTS: CTX increased and iCa decreased similarly in response to
      exercise under all test conditions. When compared with placebo, calcium
      supplementation before exercise attenuated the increase in PTH (mean +/- SE: 55.8
      +/- 15.0 vs 74.0 +/- 14.2 pg.mL(-1), P = 0.04); there was a similar trend (58.0
      +/- 17.4, P = 0.07) for calcium supplementation during exercise. There were no
      effects of calcium on changes in CTX, BAP, and iCa. CONCLUSIONS: Calcium
      supplementation before exercise attenuated the disruption of PTH. Further
      research is needed to determine the effects of repeated increases in PTH and CTX
      on bone (i.e., exercise training) and whether calcium supplementation can
      diminish any exercise-induced demineralization.

PMID- 20798656
TI  - Lower extremity kinematics in runners with patellofemoral pain during a prolonged
      run.
AB  - PURPOSE: Investigate lower extremity kinematics in runners with patellofemoral
      pain (PFP) syndrome during a prolonged run. METHODS: For this study, 20 runners
      with PFP and 20 uninjured controls performed a prolonged run on a treadmill at a
      self-selected pace. The run ended based on HR, perceived exertion, or level of
      knee pain. Kinematic data were analyzed at the beginning and at the end of the
      run. RESULTS: The PFP group demonstrated less peak knee flexion, peak hip
      adduction, eversion excursion, peak knee flexion velocity, peak hip adduction
      velocity, and peak hip internal rotation velocity compared with controls. A
      significant main effect for time indicated that increases in most kinematic
      variables occurred at the end of the run. Interestingly, five runners with PFP
      displayed atypical motions of knee valgus and eight displayed hip abduction
      during the first half of stance. CONCLUSIONS: The PFP group as a whole displayed
      less overall motion compared with controls. This may be indicative of a strategy
      aimed at limiting lower extremity movement to reduce pain. However, increases in
      joint motion occurred at the end of the run where pain levels were greatest.
      Three distinct PFP subgroups were noted, and each demonstrated unique kinematic
      mechanisms that may be associated with PFP. In the knee valgus subgroup,
      increased knee valgus and decreased peak motions were noted in other joints. In
      the hip abduction subgroup, less knee flexion and motion overall was noted. In
      the subgroup that displayed typical first half patterns (knee and hip adduction),
      increased hip internal rotation and decreased knee internal rotation were
      observed. These results suggest that several different kinematic mechanisms
      related to PFP may exist.

PMID- 20798657
TI  - No association between ACE gene variation and endurance athlete status in
      Ethiopians.
AB  - PURPOSE: The most widely studied candidate gene for endurance performance is the
      angiotensin-converting enzyme (ACE) gene. The best endurance runners in the world
      hail from Kenya and Ethiopia, so the lack of association between the ACE gene and
      elite endurance athlete status we previously reported in Kenyans requires
      replication in Ethiopians. METHODS: DNA was extracted from buccal swabs collected
      from subjects filling four groups: elite endurance runners from the Ethiopian
      national athletics team specializing in 5 km to marathon distances (n = 76),
      controls demographically matched to the elite endurance athletes (n = 410),
      controls representing the general Ethiopian population (n = 317), and sprint and
      power event athletes from the Ethiopian national athletics team (n = 38). ACE I/D
      and A22982G (rs4363) genotype frequencies were determined for each of these
      groups, and differences between groups were assessed using chi(2) tests. RESULTS:
      There were no significant deviations from Hardy-Weinberg equilibrium in endurance
      athletes or either control group. Endurance athletes did not differ significantly
      in ACE I/D genotype frequency when compared with the endurance athlete-matched
      control group (P = 0.16), general controls (P = 0.076), or sprint and power
      athletes (P = 0.39) (endurance athletes: 15.8% II, endurance athlete-matched
      controls: 8.8% II, general controls: 7.6% II, sprint and power athletes: 10.5%
      II). Similarly, no significant differences were found in ACE A22982G genotype
      between groups (endurance athletes: 13.2% AA, endurance athlete-matched controls:
      12.2% AA, general controls: 12.0% AA, sprint and power athletes: 13.2%; endurance
      athletes vs endurance athlete-matched controls: P = 0.97, endurance athletes vs
      general controls: P = 0.95, endurance athletes vs sprint and power athletes: P =
      0.52). CONCLUSIONS: As previously shown in elite Kenyan athletes, ACE I/D and
      A22982G polymorphisms are not associated with elite endurance athlete status in
      Ethiopians.

PMID- 20798658
TI  - Influence of knowledge of sprint number on pacing during repeated-sprint
      exercise.
AB  - PURPOSE: The anticipation of exercise-induced stress influences performance
      during continuous exercise. However, not all exercise is continuous. This study
      explores the influence of prior knowledge of sprint number on mechanical work,
      surface EMG, and RPE during repeated-sprint exercise (RSE). METHODS: Fourteen
      athletes performed three RSE in random order. In one trial, subjects were
      informed that they would perform ten 6-s cycle sprints (with 24 s of rest) and
      then completed 10 sprints (control trial, CL). In a second trial, subjects were
      told to perform five sprints, but after the fifth sprint, they were asked to
      perform an additional five sprints (deception trial, DC). In a third trial,
      subjects were not told how many sprints they would be performing but were stopped
      after 10 sprints (unknown trial, UN). Data were recorded for every sprint.
      RESULTS: Both the initial sprint work and work accumulated during the first five
      sprints were greater (6.5%, P < 0.05) in the DC than in the CL and UN trials.
      Furthermore, the work accumulated during the ten sprints was lower (4.0%, P <
      0.05) in the UN trial than in the two other trials. The EMG was greater (P <
      0.05) in the DC than in the CL and UN trials during the initial sprint (8.8%) and
      during the first five sprints (9.1%). The sprint-induced decrease in EMG and work
      occurred earlier in the UN trial compared with the CL and DC trials. The RPE
      profile was similar in all trials. CONCLUSIONS: Results demonstrate that pacing
      occurs during short repeated-sprint efforts in anticipation of the number of
      sprints that are included in the trial.

PMID- 20798659
TI  - Pedaling technique and energy cost in cycling.
AB  - PURPOSE: Because cycling is an extreme endurance sport, energy saving and
      therefore efficiency is of importance for performance. It is generally believed
      that gross efficiency (GE) is affected by pedaling technique. A measurement of
      pedaling technique has traditionally been done using force effectiveness ratio
      (FE; ratio of effective force and total force). The aim of the present study was
      to investigate the relationship among GE, FE, and a new technique parameter, dead
      center (DC) size in competitive cyclists. METHOD: Twenty-one competitive cyclists
      cycled for 10 min at approximately 80% VO(2max) at a freely chosen cadence (FCC).
      GE, FE ratio, and DC size were calculated from oxygen consumption and propulsive
      force recordings. RESULTS: Mean work rate was 279 W, mean FCC was 93.1 rpm, and
      mean GE was 21.7%. FE was 0.47 and 0.79 after correction for inertial forces; DC
      was 27.3% and 25.7%, respectively. DC size correlated better with GE (r = 0.75)
      than with the FE ratio (r = 0.50). Multiple regressions revealed that DC size was
      the only significant (P = 0.001) predictor for GE. Interestingly, DC size and FE
      ratio did not correlate with each other. CONCLUSIONS: DC size is a pedaling
      technique parameter that is closely related to energy consumption. To generate
      power evenly around the whole pedal, revolution may be an important energy-saving
      trait.

PMID- 20798660
TI  - Effect of increased dietary protein on tolerance to intensified training.
AB  - PURPOSE: The purpose of the present study was to examine the effect of increased
      protein intake on short-term decrements in endurance performance during a block
      of high-intensity training. METHODS: Trained male cyclists (VO(2max) = 64.2 +/-
      6.5 mL.kg(-1).min(-1)) completed two 3-wk trials both divided equally into normal
      (NOR), intensified (INT), and recovery (REC) training. In a counterbalanced
      crossover experimental design, cyclists received either a high-protein (PRO; 3 g
      protein.kg(-1) body mass (BM).d(-1)) or a normal diet (CON; 1.5 g protein.kg(-1)
      BM.d(-1)) during INT and REC. Dietary carbohydrate content remained constant at 6
      g.kg(-1) BM.d(-1). Energy balance was maintained during each training week.
      Endurance performance was assessed with a VO(2max) test and a preloaded time
      trial. Alterations in blood metabolite responses to exercise were measured at
      rest, during, and after exercise. Cyclists completed the Daily Analysis of Life
      Demands for Athletes (DALDA) questionnaire each day. RESULTS: Increased dietary
      protein intake led to a possible attenuation (4.3%; 90% confidence limits
      *//5.4%) in the decrement in time trial performance after a block of high
      intensity training compared with NOR (PRO = 2639 +/- 350 s; CON = 2555 +/- 313
      s). Restoration of endurance performance during recovery training possibly
      benefited (2.0%; *//4.9%) from additional protein intake. Frequency of symptoms
      of stress described as "worse than normal" reported after a block of high
      intensity training was very likely (97%) attenuated (17; +/-11 AUC of "a" scores
      part B, DALDA for INT + REC) by increasing the protein content of the diet. No
      discernable changes in blood metabolite concentrations were observed in PRO.
      CONCLUSIONS: Additional protein intake reduced symptoms of psychological stress
      and may result in a worthwhile amelioration of the performance decline
      experienced during a block of high-intensity training.

PMID- 20798661
TI  - Recovery of oxygen consumption after maximal exercise in children.
AB  - PURPOSE: The period of early recovery after exercise is characterized by a rapid
      payback of the oxygen debt incurred during exercise. The purpose of this study
      was to test the hypothesis that the oxygen consumption (VO(2)) decline during the
      first minute of recovery after exercise will be faster in children with a higher
      peak VO(2). METHODS: We performed a clinically indicated bicycle exercise test in
      203 children, aged 15.5 +/- 3.2 yr; 33 had healthy heart/minimal heart disease,
      59 had left-sided heart disease, 92 had right-sided heart disease, and 19 had
      postoperative single ventricle. VO(2) was recorded at peak exercise and at 20,
      40, and 60 s of recovery. RESULTS: Peak VO(2) in the study cohort was 30.1 +/-
      8.5 mL.kg(-1).min(-1) and fell to 24.3 +/- 6.7, 19.5 +/- 4.9, and 15.3 +/- 4.0
      mL.kg(-1).min(-1) at 20, 40, and 60 s of recovery, respectively. VO(2) recovery
      was slower in children with right-sided heart disease and single ventricle
      compared with the other 2 groups and was faster in younger children, boys,
      children with a higher peak VO(2), and in those with a lower RER at peak
      exercise. In the linear regression analysis, the slope of VO(2) decline during
      the first minute of recovery was most strongly associated with the peak VO(2)
      (R(2) = 0.786, P < 0.001). The only other variable that added to the explained
      variance was peak RER (R(2) = 0.796, P = 0.004). CONCLUSIONS: VO(2) decline
      during the first minute of recovery after maximum exercise is faster in children
      with higher peak VO(2). VO(2) recovery may be a useful tool in assessing
      cardiopulmonary health in children.

PMID- 20798662
TI  - Markers of chronic inflammation with short-term changes in physical activity.
AB  - PURPOSE: Regular exercise is inversely related to markers of chronic
      inflammation, but we do not know to what extent these changes are the product of
      recent exercise behavior. The aim of the present investigation was to examine the
      stability of markers of chronic inflammation in the face of short-term positive
      and negative changes in physical activity in middle-aged men. METHODS: Two
      studies were conducted using a randomized counterbalanced design. In the first
      study (Study 1), eight highly active men (age = 56 +/- 5 yr, body mass index
      (BMI) = 23.3 +/- 3.2 kg.m(-2), VO(2max) = 50.7 +/- 7.0 mL.kg(-1).min(-1))
      undertook two trials; withdrawal of exercise for 1 wk versus control (normal
      exercise behavior). In the second study (Study 2), 10 sedentary men (age = 57 +/-
      2 yr, BMI = 27.9 +/- 3.6 kg.m(-2), VO(2max) = 30.4 +/- 4.6 mL.kg(-1).min(-1))
      undertook 30 min of daily walking at 60% VO(2max) for 1 wk versus control (normal
      sedentary behavior). RESULTS: The withdrawal of exercise for 1 wk in highly
      active men (Study 1) and the imposition of 1 wk of daily exercise in sedentary
      men (Study 2) did not elicit any substantial changes in the inflammatory proteins
      C-reactive protein (CRP), IL-6, and TNF-alpha and circulating leukocyte
      concentration. The differences in inflammatory proteins between active (Study 1)
      and sedentary (Study 2) men were marked; for example, baseline CRP was 0.85 +/-
      0.79 and 3.02 +/- 2.30 mg.L(-1), respectively. CONCLUSIONS: The inflammatory
      markers CRP, IL-6, and TNF-alpha are stable and not affected by large short-term
      positive or negative alterations in exercise behavior. This stability strengthens
      the use of these markers in clinical and research settings because differences
      and changes are not simply the product of recent exercise behavior.

PMID- 20798663
TI  - Physical activity and hypertensive disorders of pregnancy among Hispanic women.
AB  - PURPOSE: Prior studies of the association between physical activity and risk of
      hypertensive disorders of pregnancy have been conflicting, failed to assess total
      physical activity, and included few Hispanic women, the largest minority group in
      the United States with the highest birth rates. METHODS: We examined this
      association among 1043 participants in the Latina Gestational Diabetes Mellitus
      Study, a prospective cohort of predominantly Puerto Rican prenatal care patients
      conducted from 2000 to 2004 in western Massachusetts. Physical activity before
      and in early pregnancy was assessed by bilingual interviewers using a modified
      version of the Kaiser Physical Activity Survey. RESULTS: Fifty women (4.8%) were
      diagnosed with hypertensive disorders of pregnancy and 30 (2.9%) with
      preeclampsia. In multivariable analyses, there was a statistically significant
      trend of decreasing risk of hypertensive disorders with increasing
      sports/exercise in early pregnancy (P(trend) = 0.04). High levels of early
      pregnancy active living activity (odds ratio (OR) = 0.4, 95% confidence interval
      (CI) = 0.1-1.1, P(trend) = 0.07) and household/care giving activity (OR = 0.4,
      95% CI = 0.1-1.3, P(trend) = 0.07) were associated with a 60% reduction in risk
      of hypertensive disorders relative to low levels; however, these associations
      were of marginal statistical significance. High levels of total physical activity
      (OR = 0.3, 95% CI = 0.1-1.0, P(trend) = 0.06) in early pregnancy were associated
      with a 70% reduction in the risk of hypertensive disorders relative to low
      levels; however, this association was also of marginal statistical significance.
      Prepregnancy physical activity was not associated with hypertensive disorders.
      CONCLUSIONS: These results in a Hispanic population, although based on small
      numbers of cases, corroborate previous studies suggesting that recreational
      activity in early pregnancy reduces the risk of hypertensive disorders of
      pregnancy.

PMID- 20798664
TI  - Hypothalamic suppression during adolescence varies by bone envelope.
AB  - PURPOSE: The purposes of this study were to suppress estradiol levels in
      adolescent (postpubertal rats) using gonadotropin-releasing hormone antagonist
      (GnRH-a) injections and to determine the changes in bone structure and mechanical
      strength. METHODS: In an Institutional Animal Care and Use Committee-approved
      study, female rats at 23 d of age were assigned to a baseline group (BL65; n =
      10) sacrificed on day 65, a control group (Control; n = 15) sacrificed on day 90,
      or an experimental group (AMEN; n = 9) sacrificed on day 90 that received daily
      injections of GnRH-a for a 25-d period from 65 to 90 d of age (2.5 mg.kg(-1) per
      dose). RESULTS: Body weights were similar on day 65; however, the AMEN group was
      significantly heavier than the Control group (17%, P = 0.001) on day 90. In the
      AMEN rats relative to the Control group, plasma estradiol levels were reduced by
      36% (P = 0.0001) and plasma insulin-like growth factor 1 levels were 24% higher
      (P = 0.003). In the femur, there was no change in periosteal bone apposition or
      total cross-sectional area. The marrow area increased by 13.7% (P = 0.05)
      resulting in a 7.8% decrease in relative cortical area (P = 0.012), and
      endocortical bone formation rate increased by 39.4% (P = 0.04). Trabecular volume
      and number decreased by 51.5% (P = 0.0003) and 49.5% (P = 0.0003), respectively.
      The absolute peak moments of the tibiae and femurs were unchanged in the AMEN
      group relative to the Control group, but these were reduced by 8.8% (P = 0.03)
      and 7.5% (P = 0.09), respectively, when normalized by body weight. CONCLUSIONS:
      Suppression of estradiol by 25 d of GnRH-a administration to 65-d-old
      (postpubertal) rats reduced trabecular volume and number by about 50%, increased
      endocortical bone turnover, and reduced relative cortical thickness without
      changing tibial and femoral total area. These changes in bone structure were
      associated with no change in absolute mechanical strength possibly because of
      increases in body weight or in insulin-like growth factor 1 concentrations.

PMID- 20798665
TI  - Postexercise water immersion increases short-term food intake in trained men.
AB  - PURPOSE: The performance of exercise while immersed in cold water has been shown
      to influence energy intake in the subsequent meal. In addition, cold water
      immersion (CWI) itself has been shown to reduce the concentration of the hormone
      leptin, high concentrations of which signal satiety. Taken together, these
      findings raise the question of whether the common practice of postexercise CWI by
      athletes acutely affects energy intake. Hence, this study investigated the acute
      effect of CWI after exercise on subsequent energy intake and macronutrient
      preferences as well as the circulating levels of a range of appetite-related
      hormones. METHODS: Ten physically active men participated in three randomized,
      counterbalanced trials consisting of 40 min of treadmill running (70% VO(2peak)),
      followed by 20 min of CWI (15 degrees C), neutral water immersion (NWI; 33
      degrees C), or a resting control with no immersion (CON). Participants were then
      given a 30-min access to a buffet-type breakfast of precisely known quantity and
      nutrient composition from which they could consume ad libitum. RESULTS:
      Participants consumed significantly more energy after both CWI (mean +/- SD =
      4893 +/- 1554 kJ, P = 0.006) and NWI (5167 +/- 1975 kJ, P = 0.010) compared with
      CON (4089 +/- 1585 kJ). However, there was no significant difference in total
      energy intake between the CWI and the NWI trials (P = 0.595). These changes were
      associated with a significant interaction effect of time and trial on both leptin
      (P = 0.045) and active ghrelin (P = 0.046). CONCLUSION: Postexercise water
      immersion is associated with higher energy intake in the subsequent meal compared
      with CON. This is an important consideration for trained men using water
      immersion as a method of recovery from exercise.

PMID- 20798666
TI  - The COL5A1 gene: a novel marker of endurance running performance.
AB  - BACKGROUND: Running economy, a key component of endurance ability, has been shown
      to be associated with flexibility. Increased stiffness (inflexibility) may
      improve running economy and therefore endurance running ability. The COL5A1 gene,
      which encodes the alpha1-chain of type V collagen, was found to associate with
      measures of flexibility. Type V collagen is a quantitatively minor fibrillar
      collagen, which is believed to regulate fibrillogenesis within tendons and other
      connective tissue. PURPOSE: The aim of this study was therefore to determine
      whether the COL5A1 gene is associated with endurance performance. METHODS: Three
      hundred thirteen Caucasian male participants who completed either the 2006 or the
      2007 226-km South African Ironman triathlon (3.8-km swim, 180-km bike, and 42.2
      km run) participated in this study. All participants were genotyped for the
      COL5A1 BstUI restriction fragment length polymorphism (RFLP). RESULTS: The COL5A1
      BstUI RFLP was significantly associated with time to complete the running
      component of the triathlon. Participants with a TT genotype completed the running
      component of the race significantly faster than individuals with a CC genotype (P
      = 0.019; mean +/- SD: TT = 294.2 +/- 52.1 min, CC = 307.4 +/- 48.6 min). In
      addition, there was a significant linear trend (P = 0.020) in the CC genotype
      distribution when the run times were divided into the fastest (13%), middle
      (17%), and slowest (25%) tertiles. There were no significant genotype differences
      for time to complete the swim, the bike, or the overall race. COL5A1 BstUI RFLP,
      body mass index, age, and 15 wk of running training history predicted 30% of the
      variance in running performance. CONCLUSION: This is the first study to identify
      the COL5A1 BstUI RFLP as a marker for endurance running performance. Further
      studies are required to replicate these findings.

PMID- 20798667
TI  - Estimates of deaths associated with seasonal influenza --- United States, 1976
      2007.
AB  - Influenza infections are associated with thousands of deaths every year in the
      United States, with the majority of deaths from seasonal influenza occurring
      among adults aged >or=65 years. For several decades, CDC has made annual
      estimates of influenza-associated deaths, which have been used in influenza
      research and to develop influenza control and prevention policy. To update
      previously published estimates of the numbers and rates of influenza-associated
      deaths during 1976-2003 by adding four influenza seasons through 2006-07, CDC
      used statistical models with data from death certificate reports. National
      mortality data for two categories of underlying cause of death codes, pneumonia
      and influenza causes and respiratory and circulatory causes, were used in
      regression models to estimate lower and upper bounds for the number of influenza
      associated deaths. Estimates by seasonal influenza virus type and subtype were
      examined to determine any association between virus type and subtype and the
      number of deaths in a season. This report summarizes the results of these
      analyses, which found that, during 1976-2007, estimates of annual influenza
      associated deaths from respiratory and circulatory causes (including pneumonia
      and influenza causes) ranged from 3,349 in 1986-87 to 48,614 in 2003-04. The
      annual rate of influenza-associated death in the United States overall during
      this period ranged from 1.4 to 16.7 deaths per 100,000 persons. The findings also
      indicated the wide variation in the estimated number of deaths from season to
      season was closely related to the particular influenza virus types and subtypes
      in circulation.

PMID- 20798668
TI  - Tobacco use among middle and high school students --- United States, 2000-2009.
AB  - Tobacco use continues to be the single leading preventable cause of death and
      disease in the United States. More than 80% of established adult smokers begin
      smoking before age 18 years. To monitor trends in tobacco use among middle and
      high school students, CDC analyzed 2000-2009 data from the National Youth Tobacco
      Survey (NYTS), a school-based survey that collects information on tobacco use and
      related behaviors and attitudes from middle school (grades 6-8) and high school
      (grades 9-12) students. This analysis indicated that in 2009, 8.2% of middle
      school students and 23.9% of high school students reported current use of any
      tobacco product; 5.2% of middle school students and 17.2% of high school students
      reported current use of cigarettes. Overall prevalence did not decrease from 2006
      to 2009 for use of any tobacco product among either group. During 2000-2009, the
      prevalence of current tobacco use among middle school students declined (15.1% to
      8.2%), as did current cigarette use (11.0% to 5.2%) and cigarette smoking
      experimentation (29.8% to 15.0%). Similar trends were observed for high school
      students (current tobacco use: 34.5% to 23.9%; current cigarette use: 28.0% to
      17.2%; cigarette smoking experimentation: 39.4% to 30.1%). Overall, no change in
      susceptibility to initiate cigarette smoking was observed for either group. To
      further decrease tobacco use and susceptibility to use among youths, restrictions
      on advertising, promotion, and availability of tobacco products to youths should
      be combined with full implementation of evidence-based, communitywide,
      comprehensive tobacco control policies.

PMID- 20798669
TI  - Changes in measurement of Haemophilus influenzae serotype b (Hib) vaccination
      coverage --- National Immunization Survey, United States, 2009.
AB  - The National Immunization Survey (NIS) has introduced a new method for measuring
      Haemophilus influenzae serotype b (Hib) vaccination coverage. Since its inception
      in 1994, NIS has considered a child aged 19-35 months to be fully vaccinated with
      Hib vaccine if the child had received 3 or more doses of any Hib-containing
      vaccine (3+Hib), regardless of vaccine product type received. However, for some
      Hib vaccine product types, 4 doses are needed to be fully vaccinated. Because NIS
      data have not distinguished between Hib vaccine product types, a child who
      received 3 doses of a vaccine product that requires 4 doses was misclassified as
      fully vaccinated. Since January 2009, NIS has requested that vaccination
      providers report data on Hib vaccine product types. Using this new information,
      two new measures were created: 1) primary series completed and 2) fully
      vaccinated (primary series completed plus booster dose). To determine the effects
      of the new method, CDC used preliminary data from the first half of 2009 NIS to
      compare the new measures with the previous 3+Hib measure. The findings, which
      were influenced by a nationwide shortage of certain Hib vaccine types, indicated
      that 92.9% of children aged 19-35 months in the United States had received the
      primary Hib series according to interim recommendations of the Advisory Committee
      on Immunization Practices (ACIP), and 56.9% were fully vaccinated. Using the
      previous method, 82.9% were fully vaccinated (3+Hib). When interpreting Hib
      vaccination coverage estimates and analyzing trends with NIS Hib vaccination
      coverage data in the future, analysts and state immunization programs should be
      aware of this change in Hib measurement.

PMID- 20798670
TI  - Mediators of maternal depression and family structure on child BMI: parenting
      quality and risk factors for child overweight.
AB  - Risk factors for child obesity may be influenced by family environment, including
      maternal depression, family structure, and parenting quality. We tested a path
      model in which maternal depression and single parent status are associated with
      parenting quality, which relates to three risk factors for child obesity: diet,
      leisure, and sedentary behavior. Participants included 4,601 5th-grade children
      and their primary caregivers who participated in the Healthy Passages study.
      Results showed that associations of maternal depression and single parenthood
      with child BMI are mediated by parenting quality and its relation to children's
      leisure activity and sedentary behavior. Interventions for child obesity may be
      more successful if they target family environment, particularly parenting quality
      and its impact on children's active and sedentary behaviors.

PMID- 20798672
TI  - Arnold Lester Demain: a good friend, an outstanding scientist and a valuable
      professor.

PMID- 20798674
TI  - Happiness: origins, forms, and technical relevance.
AB  - By critically reviewing Freud's views on happiness, and also those of Helene
      Deutsch, Bertram Lewin, Melanie Klein, and Heinz Kohut, the author evolves a
      complex and multilayered perspective on the phenomenon. He categorizes happiness
      into four related and occasionally overlapping varieties: pleasure-based
      happiness (elation), assertion-based happiness (joy), merger-based happiness
      (ecstasy), and fulfillment-based happiness (contentment). After entering some
      caveats and drawing from his clinical experience, the author then demonstrates
      the relevance of these ideas to the conduct of psychotherapy and psychoanalysis.

PMID- 20798673
TI  - Dop functions as a depupylase in the prokaryotic ubiquitin-like modification
      pathway.
AB  - Post-translational modification of proteins with prokaryotic ubiquitin-like
      protein (Pup) is the bacterial equivalent of ubiquitination in eukaryotes.
      Mycobacterial pupylation is a two-step process in which the carboxy-terminal
      glutamine of Pup is first deamidated by Dop (deamidase of Pup) before ligation of
      the generated gamma-carboxylate to substrate lysines by the Pup ligase PafA. In
      this study, we identify a new feature of the pupylation system by demonstrating
      that Dop also acts as a depupylase in the Pup proteasome system in vivo and in
      vitro. Dop removes Pup from substrates by specific cleavage of the isopeptide
      bond. Depupylation can be enhanced by the unfolding activity of the mycobacterial
      proteasomal ATPase Mpa.

PMID- 20798675
TI  - A century of silence.
AB  - This paper addresses how crimes of genocide go beyond a need for naked power,
      economic aggrandizement, or territorial conquest. Such crimes involve psychogenic
      and psychodynamic underpinnings that can be terrifying to contemplate. Yet their
      psychological study is essential. The Armenian genocide has been taken as a point
      of reference. Because the Armenian genocide has resulted in nearly a century-long
      effort of perpetrator denial, it can provide an important case study of how long
      standing trauma and denial reinforce each other and illuminate each other. As a
      result, this genocide has aptly been called the "secret genocide," the
      "unremembered genocide," and a "crime without a name." The author holds that
      genocidal trauma (and trauma in general) is contagious and the contagion is
      likely to be insidious. All who come in contact with it can come away marked,
      including victim, victim families and progeny, observers, advocates, researchers,
      and yes, perpetrators.

PMID- 20798676
TI  - First they came... a response to Danielian's "A century of silence".

PMID- 20798677
TI  - Shame veiled and unveiled: the shame affect and its re-emergence in the clinical
      setting.
AB  - The paper examines the psychoanalytic theory of shame and the importance of
      developmental aspects of the shame affect. In a clinical setting, the discovery
      of the shame affect, stemming from unconscious and early traumatic situations, is
      an important and useful approach in helping the patient access painful memories
      and defenses against them. The defenses disguise the underlying shame affect;
      furthermore, vision is being bound up with the searing painful affect of shame.
      The anticipatory dread of scornful gaze of another person, similar to objective
      self-awareness can cause mortification. Fear of mortification and being exposed
      emerges in the clinical setting. Through the recognition of enactments in the
      transference and countertransference interchange, the analyst helps the patient
      working through them. Several case vignettes demonstrate these important
      concepts. Finally, the author discusses how shame in certain situations can be a
      powerful, positive motivator for human interactions.

PMID- 20798678
TI  - Repetitive maladaptive behavior: beyond repetition compulsion.
AB  - Maladaptive behavior that repeats, typically known as repetition compulsion, is
      one of the primary reasons that people seek psychotherapy. However, even with
      psychotherapeutic advances it continues to be extremely difficult to treat.
      Despite wishes and efforts to the contrary repetition compulsion does not
      actually achieve mastery, as evidenced by the problem rarely resolving without
      therapeutic intervention, and the difficulty involved in producing treatment
      gains. A new framework is proposed, whereby such behavior is divided into
      behavior of non-traumatic origin and traumatic origin with some overlap
      occurring. Repetitive maladaptive behavior of non-traumatic origin arises from an
      evolutionary-based process whereby patterns of behavior frequently displayed by
      caregivers and compatible with a child's temperament are acquired and repeated.
      It has a familiarity and ego-syntonic aspect that strongly motivates the person
      to retain the behavior. Repetitive maladaptive behavior of traumatic origin is
      characterized by defensive dissociation of the cognitive and emotional components
      of trauma, making it very difficult for the person to integrate the experience.
      The strong resistance of repetitive maladaptive behavior to change is based on
      the influence of both types on personality, and also factors specific to each.
      Psychotherapy, although very challenging at the best of times, can achieve the
      mastery wished and strived for, with the aid of several suggestions provided.

PMID- 20798679
TI  - Erotic and antierotic transference.

PMID- 20798680
TI  - The absence of the third and murderous dyads in male to female erotic
      transference.

PMID- 20798681
TI  - Fearful symmetry: pleasure, joy and desire in the psychoanalytic relationship.

PMID- 20798685
TI  - Sphingosine-1-phosphate phosphohydrolase-1 regulates ER stress-induced autophagy.
AB  - The sphingolipid metabolites ceramide and sphingosine-1-phosphate (S1P) have
      recently been implicated in autophagy. In this study, we report that depletion of
      sphingosine-1-phosphate phosphohydrolase-1 (SPP1), an endoplasmic reticulum (ER)
      resident enzyme that specifically dephosphorylates S1P, induced autophagy.
      Although the mammalian target of rapamycin and class III phosphoinositide 3
      kinase/Beclin-1 pathways were not involved and this autophagy was p53
      independent, C/EBP homologous protein, BiP, and phospho-eucaryotic translation
      initiation factor-2alpha, and cleavage of procaspases 2 and 4, downstream targets
      of ER stress, were increased after SPP1 depletion. Autophagy was suppressed by
      depletion of protein kinase regulated by RNA-like ER kinase (PERK), inositol
      requiring transmembrane kinase/endonuclease-1alpha, or activating transcription
      factor 6, three sensors of the unfolded protein response (UPR) to ER stress.
      Autophagy triggered by downregulation of SPP1 did not lead to apoptosis but
      rather stimulated, in a PERK dependent manner, the survival signal Akt, whose
      inhibition then sensitized cells to apoptosis. Although depletion of SPP1
      increased intracellular levels of S1P and its secretion, activation of cell
      surface S1P receptors did not induce autophagy. Nevertheless, increases in
      intracellular pools of S1P, but not dihydro-S1P, induced autophagy and ER stress.
      Thus, SPP1, by regulating intracellular S1P homeostasis, can control the UPR and
      ER stress-induced autophagy.

PMID- 20798686
TI  - Involvement of NF-kappaB/miR-448 regulatory feedback loop in chemotherapy-induced
      epithelial-mesenchymal transition of breast cancer cells.
AB  - The epithelial-mesenchymal transition (EMT) induced by chemotherapeutic agents
      promotes malignant tumor progression; however, the mechanism underlying the drug
      induced EMT remains unclear. In this study, we reported that miR-448 is the most
      downregulated microRNA following chemotherapy. Suppression of miR-448 correlated
      with EMT induction in breast cancer in vitro and in vivo. With the use of
      chromatin immunoprecipitation-seq analysis, we demonstrated that miR-448
      suppression induces EMT by directly targeting special AT-rich sequence-binding
      protein-1 (SATB1) mRNA, leading to elevated levels of amphiregulin and thereby,
      increasing epidermal growth factor receptor (EGFR)-mediated Twist1 expression, as
      well as nuclear factor kappaB (NF-kappaB) activation. On the other hand, we also
      found that the adriamycin-activated NF-kappaB directly binds the promoter of miR
      448 suppressing its transcription, suggesting a positive feedback loop between NF
      kappaB and miR-448. Furthermore, all patients who received cyclophosphamide (CP),
      epirubicin plus taxotere/CP, epirubicin plus 5-fluorouracil chemotherapy showed
      miR-448 suppression, an increased SATB1, Twist1 expression and acquisition of
      mesenchymal phenotypes. These findings reveal an underlying regulatory pathway,
      in which the autoregulation between NF-kappaB and miR-448 is important for
      restrain miR-448 suppression upon chemotherapy and may have a role in the
      regulation of chemotherapy-induced EMT. Disruption of the NF-kappaB-miR-448
      feedback loop during clinical treatment may improve the chemotherapy response of
      human breast cancers in which EMT is a critical component.

PMID- 20798687
TI  - Cell-autonomous regulation of hematopoietic stem cell cycling activity by ATP.
AB  - Extracellular nucleotides regulate many cellular functions through activation of
      purinergic receptors in the plasma membrane. Here, we show that in hematopoietic
      stem cell (HSC), ATP is stored in vesicles and released in a calcium-sensitive
      manner. HSC expresses ATP responsive P2X receptors and in vitro pharmacological
      P2X antagonism restrained hematopoietic progenitors proliferation, but not
      myeloid differentiation. In mice suffering from chronic inflammation, HSCs were
      significantly expanded and their cycling activity was sensitive to treatment with
      the P2X antagonist periodate-oxidized 2,3-dialdehyde ATP. Our results indicate
      that ATP acts as an autocrine stimulus in regulating HSCs pool size.

PMID- 20798688
TI  - A positive role for c-Abl in Atm and Atr activation in DNA damage response.
AB  - DNA damage triggers Atm- and/or Atr-dependent signaling pathways to control cell
      cycle progression, apoptosis, and DNA repair. However, how Atm and Atr are
      activated is not fully understood. One of the downstream targets of Atm is non
      receptor tyrosine kinase c-Abl, which is phosphorylated and activated by Atm. The
      current view is that c-Abl relays pro-apoptotic signals from Atm to p73 and p53.
      Here we show that c-Abl deficiency resulted in a broad spectrum of defects in
      cell response to genotoxic stress, including activation of Chk1 and Chk2,
      activation of p53, nuclear foci formation, apoptosis, and DNA repair, suggesting
      that c-Abl might also act upstream of the DNA damage-activated signaling cascades
      in addition to its role in p73 and p53 regulation. Indeed, we found that c-Abl is
      required for proper activation of both Atm and Atr. c-Abl is bound to the
      chromatin and shows enhanced interaction with Atm and Atr in response to DNA
      damage. c-Abl can phosphorylate Atr on Y291 and Y310 and this phosphorylation
      appears to have a positive role in Atr activation under genotoxic stress. These
      findings suggest that Atm-mediated c-Abl activation in cell response to double
      stranded DNA breaks might facilitate the activation of both Atm and Atr to
      regulate their downstream cellular events.

PMID- 20798691
TI  - Methylmalonic aciduria and homocystinuria-associated maculopathy.

PMID- 20798689
TI  - SUMO-modified nuclear cyclin D1 bypasses Ras-induced senescence.
AB  - Oncogene-induced senescence represents a key tumor suppressive mechanism. Here,
      we show that Ras oncogene-induced senescence can be mediated by the recently
      identified haploinsufficient tumor suppressor apoptosis-stimulating protein of
      p53 (ASPP) 2 through a novel and p53/p19(Arf)/p21(waf1/cip1)-independent pathway.
      ASPP2 suppresses Ras-induced small ubiquitin-like modifier (SUMO)-modified
      nuclear cyclin D1 and inhibits retinoblastoma protein (Rb) phosphorylation. The
      lysine residue, K33, of cyclin D1 is a key site for this newly identified
      regulation. In agreement with the fact that its nuclear localization is required
      for its oncogenic activity, we show that nuclear cyclin D1 is far more potent
      than wild-type (WT) cyclin D1 in bypassing Ras-induced senescence. Thus, this
      study identifies SUMO modification as a positive regulator of nuclear cyclin D1,
      and reveals a new way by which cell cycle entry and senescence are regulated.

PMID- 20798692
TI  - Acute-angle closure glaucoma as the presenting sign of hypertensive crisis.

PMID- 20798690
TI  - Mcl-1 downregulation by pro-inflammatory cytokines and palmitate is an early
      event contributing to beta-cell apoptosis.
AB  - Pancreatic beta-cell apoptosis is a key feature of diabetes mellitus and the
      mitochondrial pathway of apoptosis is a major mediator of beta-cell death. We
      presently evaluated the role of the myeloid cell leukemia sequence 1 (Mcl-1), an
      antiapoptotic protein of the Bcl-2 family, in beta-cells following exposure to
      well-defined beta-cell death effectors, for example, pro-inflammatory cytokines,
      palmitate and chemical endoplasmic reticulum (ER) stressors. All cytotoxic
      stresses rapidly and preferentially decreased Mcl-1 protein expression as
      compared with the late effect observed on the other antiapoptotic proteins, Bcl-2
      and Bcl-xL. This was due to ER stress-mediated inhibition of translation through
      eIF2alpha phosphorylation for palmitate and ER stressors and through the combined
      action of translation inhibition and JNK activation for cytokines. Knocking down
      Mcl-1 using small interference RNAs increased apoptosis and caspase-3 cleavage
      induced by cytokines, palmitate or thapsigargin, whereas Mcl-1 overexpression
      partly prevented Bax translocation to the mitochondria, cytochrome c release,
      caspase-3 cleavage and apoptosis induced by the beta-cell death effectors.
      Altogether, our data suggest that Mcl-1 downregulation is a crucial event leading
      to beta-cell apoptosis and provide new insights into the mechanisms linking ER
      stress and the mitochondrial intrinsic pathway of apoptosis. Mcl-1 is therefore
      an attractive target for the design of new strategies in the treatment of
      diabetes.

PMID- 20798693
TI  - Ranibizumab for subfoveal choroidal neovascularization in Bietti crystalline
      retinopathy.

PMID- 20798694
TI  - Trichotillomania following herpetic neuralgia.

PMID- 20798696
TI  - Vectoring siRNA therapeutics into the clinic.

PMID- 20798695
TI  - Arming a replicating adenovirus with osteoprotegerin reduces the tumor burden in
      a murine model of osteolytic bone metastases of breast cancer.
AB  - Most patients with advanced breast cancer develop osteolytic bone metastases,
      which have numerous complications. Because current therapies are not curative,
      new treatments are needed. Conditionally replicating adenoviruses (CRAds) are
      anticancer agents designed to infect and lyse tumor cells. However, in spite of
      their promise as selective cancer therapeutics, replicating adenoviruses have
      shown limited efficacy in the clinical setting. We hypothesized that a CRAd armed
      with osteoprotegerin (OPG) would eradicate bone metastases of breast cancer both
      directly, by oncolysis, and indirectly, by inhibiting osteoclastic bone
      resorption, and thus reducing the tumor burden. We constructed an armed CRAd (Ad5
      Delta24-sOPG-Fc-RGD) by replacing viral E3B genes with a fusion of the ligand
      binding domains of OPG and the Fc portion of human IgG1. Conditional replication
      was conferred by a 24-base pair deletion within E1A (Delta24), which prevents the
      binding of E1A to the retinoblastoma tumor suppressor/cell cycle regulator
      protein and limits replication in normal cells. Enhanced infection of cells
      expressing low levels of the primary Ad5 receptor was conferred by incorporating
      an arginine-glycine-aspartic acid (RGD) peptide sequence into the fiber knob to
      mediate binding to alpha(v) integrins. After characterization of the armed CRAd,
      we demonstrated that infection of breast cancer cells by Ad5-Delta24-sOPG-Fc-RGD
      both killed the infected cells by oncolysis and inhibited the formation of
      osteoclasts in an in vitro co-culture model. In a murine model of osteolytic bone
      metastases of breast cancer, the CRAd armed with shortened OPG (sOPG)-Fc reduced
      tumor burden in the bone and inhibited osteoclast formation more effectively than
      an unarmed CRAd.

PMID- 20798697
TI  - Evolving role of 5-alpha reductase inhibitors in chemoprevention.

PMID- 20798698
TI  - Flexible sigmoidoscopy--valuable in colorectal cancer.

PMID- 20798699
TI  - 200 mg/m(2) melphalan--the gold standard for multiple myeloma.

PMID- 20798700
TI  - The dental health of three-year-old children in Greater Glasgow, Scotland.
AB  - OBJECTIVE: To report on the dental health of three-year-old children in Greater
      Glasgow, and to examine the amount of dental caries associated with deprivation
      in this young age group. DESIGN: Dental inspections in nursery schools. SUBJECTS
      AND METHODS: The national inspection programme using BASCD criteria was extended
      to include an additional group of nursery attending three-year-olds in Greater
      Glasgow in 2006/7 and 2007/8. Caries experience was analysed by logistic
      regression models and ROC plots. RESULTS: Fourteen percent of this population was
      sampled in 2006/7 and 19% in 2007/8 (usable data n = 1,711 in 2006/7, 2,428 in
      2007/8). Mean d(3)mft was 1.1 in 2006/7 and 1.0 in 2007/8. The prevalence of
      caries experience was 26% in 2006/7 and 25% in 2007/8 (33% and 32%, respectively,
      for children in deprived areas). The adjusted odds-ratio for caries experience
      for children living in the most deprived areas was 2.90 (2.31, 3.64), p <0.001.
      There was a high rate of caries in the upper anterior teeth. CONCLUSION: It was
      feasible to conduct large scale caries surveys of three-year-olds in a nursery
      setting. Poor dental health and inequality commence early in life. Caries
      prevention should be targeted toward deprived families from birth.

PMID- 20798701
TI  - Third molar-related morbidity in deployed Service personnel.
AB  - INTRODUCTION: The minimisation of disease and non-battle injury (DNBI) is
      essential for maintaining efficiency in a fighting force. Third molar-related
      morbidity is a common cause of DNBI. With extended lines of communication in
      current military deployments, travelling for dental care is often subject to
      significant danger. MATERIAL AND METHODS: Military dental officers in Afghanistan
      and Iraq recorded data on patients presenting with third molar pathology. Related
      previous history was obtained from the individual and from the military dental
      records. RESULTS: Three hundred and three individuals presented during the 23
      month study period; 27.7% were unable to access care immediately, most commonly
      citing work pressure or lack of safe transport. Of those needing to travel, 70%
      were moved by helicopter. Pericoronitis was diagnosed in 84.4% of cases, 20.6% of
      these teeth being extracted; 53.5% of patients reported no prior symptoms, 22.7%
      with two or more episodes. There was documented evidence in military dental
      records of previous problems in 29.2% of cases. 11.3% had previously been listed
      for extraction of the presenting tooth. DISCUSSION: Dental treatment for troops
      in combat situations is fraught with difficulty. Special consideration must be
      given to the management of third molars in military personnel.

PMID- 20798702
TI  - The curate's egg.

PMID- 20798703
TI  - Resorption issues.

PMID- 20798704
TI  - Contact caries.

PMID- 20798705
TI  - Herbal remedies.

PMID- 20798706
TI  - Poorly led service.

PMID- 20798709
TI  - Chip developed to diagnose oral cancer in ten minutes.

PMID- 20798719
TI  - Preventing decay in children: dare we risk the 'risk assessment' model in
      practice?
AB  - Encouraging dental prevention seems like a logical approach given that dental
      decay is a preventable disease and while the 2006 dental contract provides
      preventive opportunities, there is confusion about the best approach to the
      prevention of decay in those children that attend their dentist. Should we
      provide prevention for all children attending their dentist (the population
      approach) or should we target those children who are at greatest risk (risk
      assessment approach)?

PMID- 20798720
TI  - Risk management in clinical practice. Part 4. Endodontics.
AB  - Endodontic procedures are challenging and technically demanding. In the UK
      standards of treatment have been shown to have fallen short of acceptable
      guidelines, laying many dentists open to litigation on questions of clinical
      negligence by patients who understand and know what should be considered as
      current best practice in this area. Failure to communicate with patients about
      the procedure and not obtaining consent for treatment is a key area of complaint,
      as is inadequate record keeping. When treatment is undertaken within the
      framework of accepted guidelines it would be very difficult for a patient to open
      a claim for clinical negligence should a failure occur. This article looks at
      potential dento-legal problems in endodontics and how, through compliance with
      best practice, they may be avoided.

PMID- 20798721
TI  - Repair or replacement of restorations: do we accept built in obsolescence or do
      we improve the evidence?
AB  - INTRODUCTION: Controversy surrounds decisions on whether to repair or replace
      defective dental restorations. The concept of built-in obsolescence, ie periodic
      replacement of dental restorations, is largely accepted as the modus operandi if
      not the default mode in restorative care. In this article we examine the current
      best available evidence underpinning the effectiveness of replacement versus
      repair of direct amalgam and resin composite restorations. METHOD: This article
      builds on two recent Cochrane systematic reviews which have reported on the
      evidence base supporting the effectiveness of replacement versus repair of
      amalgam and direct resin composites and translates the results of their research
      conclusions into recommendations for the dental clinician. RESULTS: As no
      relevant randomised controlled trials (RCTs) were identified in either of these
      systematic reviews, the evidence regarding the effectiveness of repair versus
      replacement of amalgam and composite restorations is weak and incomplete. The
      evidence as it currently stands seems to favour repair over replacement, but this
      is insufficient to make firm recommendations. CONCLUSION: In view of the absence
      of high level evidence there is a need for further well designed RCTs. To add
      value to the evidence base these trials should be conducted in a general practice
      setting which will strengthen the generalisability and applicability of the
      research conclusions and enable dentists and patients to make informed decisions.

PMID- 20798726
TI  - Summary of: the dental health of three-year-old children in Greater Glasgow,
      Scotland.
AB  - OBJECTIVE: To report on the dental health of three-year-old children in Greater
      Glasgow, and to examine the amount of dental caries associated with deprivation
      in this young age group. DESIGN: Dental inspections in nursery schools. SUBJECTS
      AND METHODS: The national inspection programme using BASCD criteria was extended
      to include an additional group of nursery attending three-year-olds in Greater
      Glasgow in 2006/7 and 2007/8. Caries experience was analysed by logistic
      regression models and ROC plots. RESULTS: Fourteen percent of this population was
      sampled in 2006/7 and 19% in 2007/8 (usable data n = 1,711 in 2006/7, 2,428 in
      2007/8). Mean d(3)mft was 1.1 in 2006/7 and 1.0 in 2007/8. The prevalence of
      caries experience was 26% in 2006/7 and 25% in 2008/9 (33% and 32%, respectively,
      for children in deprived areas). The adjusted odds-ratio for caries experience
      for children living in the most deprived areas was 2.90 (2.31, 3.64), p <0.001.
      There was a high rate of caries in the upper anterior teeth. CONCLUSION: It was
      feasible to conduct large scale caries surveys of three-year-olds in a nursery
      setting. Poor dental health and inequality commence early in life. Caries
      prevention should be targeted toward deprived families from birth.

PMID- 20798727
TI  - Summary of: third molar-related morbidity in deployed Service personnel.
AB  - INTRODUCTION: The minimisation of disease and non-battle injury (DNBI) is
      essential for maintaining efficiency in a fighting force. Third molar-related
      morbidity is a common cause of DNBI. With extended lines of communication in
      current military deployments, travelling for dental care is often subject to
      significant danger. MATERIAL AND METHODS: Military dental officers in Afghanistan
      and Iraq recorded data on patients presenting with third molar pathology. Related
      previous history was obtained from the individual and from the military dental
      records. RESULTS: Three hundred and three individuals presented during the 23
      month study period; 27.7% were unable to access care immediately, most commonly
      citing work pressure or lack of safe transport. Of those needing to travel, 70%
      were moved by helicopter. Pericoronitis was diagnosed in 84.4% of cases, 20.6% of
      these teeth being extracted; 53.5% of patients reported no prior symptoms, 22.7%
      with two or more episodes. There was documented evidence in military dental
      records of previous problems in 29.2% of cases. 11.3% had previously been listed
      for extraction of the presenting tooth. DISCUSSION: Dental treatment for troops
      in combat situations is fraught with difficulty. Special consideration must be
      given to the management of third molars in military personnel.

PMID- 20798728
TI  - Evidence summary: does dentists' fear have an adverse effect on clinical decision
      making?
AB  - Since August 2009, members of the Primary Care Dentistry Research Forum
      (http://www.dentistryresearch.org) have taken part in an online vote to identify
      questions in day-to-day practise that they felt most needed to be answered with
      conclusive research. The question which receives the most votes each month forms
      the subject of a critical appraisal of the relevant literature. Each month a new
      round of voting takes place to decide which further questions will be reviewed.
      Dental practitioners and dental care professionals are encouraged to take part in
      the voting and submit their own questions to be included in the vote by joining
      the website.The paper below details a summary of the findings of the eighth
      critical appraisal. In conclusion, the critical appraisal found no studies that
      identified the nature and extent of dentists' fears. Nor did the appraisal find
      any studies that assessed how dentists' own fears impact upon clinical decision
      making. It would appear that this subject is novel territory for primary
      research.

PMID- 20798749
TI  - Ghrelin: central nervous system sites of action in regulation of energy balance.
AB  - Ghrelin, a peptide hormone secreted by the stomach, has been shown to regulate
      energy homeostasis by modulating electrical activity of neurons in the central
      nervous system (CNS). Like many circulating satiety signals, ghrelin is a peptide
      hormone and is unable to cross the blood-brain barrier without a transport
      mechanism. In this review, we address the notion that the arcuate nucleus of the
      hypothalamus is the only site in the CNS that detects circulating ghrelin to
      trigger orexigenic responses. We consider the roles of a specialized group of CNS
      structures called the sensory circumventricular organs (CVOs), which are not
      protected by the blood-brain barrier. These areas include the subfornical organ
      and the area postrema and are already well known to be key areas for detection of
      other circulating hormones such as angiotensin II, cholecystokinin, and amylin. A
      growing body of evidence indicates a key role for the sensory CVOs in the
      regulation of energy homeostasis.

PMID- 20798750
TI  - Predictors of the progression of dementia severity in brazilian patients with
      Alzheimer's disease and vascular dementia.
AB  - Introduction. This study evaluates the progression of dementia and identifies
      prognostic risk factors for dementia. Methods. A group of 80 Brazilian community
      residents with dementia (34 with Alzheimer's disease and 46 with vascular
      dementia) was assessed over the course of 2 years. Data were analyzed with Cox
      regression survival analysis. Results. The data showed that education predicted
      cognitive decline (HR = 1.2; P < .05) when analyzed without controlling for
      vascular risk factors. After the inclusion of vascular risk factors, education
      (HR = 1.32; P < .05) and hypertension were predictive for cognitive decline (HR =
      38; P < .05), and Alzheimer's disease diagnosis was borderline predictive (P =
      .055). Conclusion. Vascular risk factors interacted with the diagnosis of
      vascular dementia. Education was a strong predictor of decline.

PMID- 20798751
TI  - Mitochondrial Thioredoxin-Glutathione Reductase from Larval Taenia crassiceps
      (Cysticerci).
AB  - Mitochondrial thioredoxin-glutathione reductase was purified from larval Taenia
      crassiceps (cysticerci). The preparation showed NADPH-dependent reductase
      activity with either thioredoxin or GSSG, and was able to perform thiol/disulfide
      exchange reactions. At 25 degrees C specific activities were 437 +/- 27 mU mg(-1)
      and 840 +/- 49 mU mg(-1) with thioredoxin and GSSG, respectively. Apparent K(m)
      values were 0.87 +/- 0.04 muM, 41 +/- 6 muM and 19 +/- 10 muM for thioredoxin,
      GSSG and NADPH, respectively. Thioredoxin from eukaryotic sources was accepted as
      substrate. The enzyme reduced H(2)O(2) in a NADPH-dependent manner, although with
      low catalytic efficiency. In the presence of thioredoxin, mitochondrial TGR
      showed a thioredoxin peroxidase-like activity. All disulfide reductase activities
      were inhibited by auranofin, suggesting mTGR is dependent on selenocysteine. The
      reductase activity with GSSG showed a higher dependence on temperature as
      compared with the DTNB reductase activity. The variation of the GSSG- and DTNB
      reductase activities on pH was dependent on the disulfide substrate. Like the
      cytosolic isoform, mTGR showed a hysteretic kinetic behavior at moderate or high
      GSSG concentrations, but it was less sensitive to calcium. The enzyme was able to
      protect glutamine synthetase from oxidative inactivation, suggesting that mTGR is
      competent to contend with oxidative stress.

PMID- 20798752
TI  - Risk of dementia associated with elevated plasma homocysteine in a latin american
      population.
AB  - The relationship between total homocysteine (tHcy) and dementia risk remains
      controversial, as the association varies among populations and dementia subtypes.
      We studied a Venezuelan population that has high prevalence of both elevated tHcy
      and dementia. We tested the hypotheses that (1) elevated tHcy is associated with
      increased dementia risk, (2) the risk is greater for vascular dementia (VaD) than
      for Alzheimer's disease (AD), and (3) a history of stroke may partly explain this
      association. 2100 participants (>/=55 years old) of the Maracaibo Aging Study
      underwent standardized neurological, neuropsychiatric, and cardiovascular
      assessments. Elevated tHcy was significantly associated with dementia, primarily
      VaD. When history of stroke and other confounding factors were taken into
      account, elevated tHcy remained a significant risk factor in older (>66 years),
      but not in younger (55-66 years) subjects. Ongoing studies of this population may
      provide insight into the mechanism by which tHcy increases risk for dementia.

PMID- 20798753
TI  - In Vitro Study of Nitric Oxide Metabolites Effects on Human Hydatid of
      Echinococcus granulosus.
AB  - Hydatidosis is characterized by the long-term coexistence of larva Echinococcus
      granulosus and its host without effective rejection. Previous studies
      demonstrated nitric oxide (NO) production (in vivo and in vitro) during
      hydatidosis. In this study, we investigated the direct in vitro effects of NO
      species: nitrite (NO(2) (-)), nitrate (NO(3) (-)) and peroxynitrite (ONOO(-)) on
      protoscolices (PSCs) viability and hydatid cyst layers integrity for 24 hours and
      48 hours. Our results showed protoscolicidal activity of NO(2) (-) and ONOO(-) 24
      hours and 3 hours after treatment with 320 muM and 80 muM respectively.
      Degenerative effects were observed on germinal and laminated layers. The
      comparison of the in vitro effects of NO species on the PSCs viability indicated
      that ONOO(-) is more cytotoxic than NO(2) (-). In contrast, NO(3) (-) has no
      effect. These results suggest possible involvement of NO(2) (-) and ONOO(-) in
      antihydatic action and point the efficacy of these metabolites as scolicidal
      agents.

PMID- 20798754
TI  - Variation in Provider Identification of Obesity by Individual- and Neighborhood
      Level Characteristics among an Insured Population.
AB  - Objective. The purpose of this study was to examine whether neighborhood- and
      individual-level characteristics affect providers' likelihood of providing an
      obesity diagnosis code in their obese patients' claims. Methods. Logistic
      regressions were performed with obesity diagnosis code serving as the outcome
      variable and neighborhood characteristics and member characteristics serving as
      the independent variables (N = 16,151 obese plan members). Results. Only 7.7
      percent of obese plan members had an obesity diagnosis code listed in their
      claims. Members living in neighborhoods with the largest proportions of Blacks
      were 29 percent less likely to receive an obesity diagnosis (P < .05). The odds
      of having an obesity diagnosis code were greater among members who were female,
      aged 44 or below, hypertensive, dyslipidemic, BMI >/= 35 kg/m(2), had a larger
      number of provider visits, or who lived in an urban area (all P < .05).
      Conclusions. Most health care providers do not include an obesity diagnosis code
      in their obese patients' claims. Rates of obesity identification were strongly
      related to individual characteristics and somewhat associated with neighborhood
      characteristics.

PMID- 20798755
TI  - Impact of cognitive impairment on functional outcome in stroke.
AB  - The aim of this study was to investigate the effect of the cognitive impairment
      on functional status in patients with subacute stroke. Fifty-two patients with
      subacute stroke were included in the study. Mini mental state examination (MMSE)
      test was used for the evaluation of cognitive status. Patients were separated
      into two groups according to their cognitive functions. Functional follow-up
      parameters were activities of daily living (ADL), global recovery and ambulation
      status. All patients were evaluated on admission to rehabilitation unit, at
      discharge and 6 months after discharge. Forty-four patients were completed the
      study. Mean age was 66 and 57 years; disease duration on admission was 4,8 and
      3,5 months in the cognitively impaired and normal groups, respectively.
      Significant improvement was found in terms of functional follow-up parameters in
      both groups at discharge (P < .05). Functional follow-up parameters did not show
      statistically significant difference between the groups. But community ambulation
      rate was higher in cognitively normal group at the sixth month visit. As a result
      of this study, inpatient rehabilitation was effective both cognitively normal and
      impaired subacute stroke patients.

PMID- 20798756
TI  - Nutritional rehabilitation: practical guidelines for refeeding the anorectic
      patient.
AB  - Weight restoration is crucial for successful treatment of anorexia nervosa.
      Without it, patients may face serious or even fatal medical complications of
      severe starvation. However, the process of nutritional rehabilitation can also be
      risky to the patient. The refeeding syndrome, a problem of electrolyte and fluid
      shifts, can cause permanent disability or even death. It is essential to identify
      at-risk patients, to monitor them carefully, and to initiate a nutritional
      rehabilitation program that aims to avoid the refeeding syndrome. A judicious,
      slow initiation of caloric intake, requires daily management to respond to
      entities such as liver inflammation and hypoglycemia that can complicate the
      body's conversion from a catabolic to an anabolic state. In addition, nutritional
      rehabilitation should take into account clinical characteristics unique to these
      patients, such as gastroparesis and slowed colonic transit, so that measures can
      be taken to ameliorate the physical discomforts of weight restoration. Adjunct
      methods of refeeding such as the use of enteral or parenteral nutrition may play
      a small but important role in a select patient group who cannot tolerate oral
      nutritional rehabilitation alone.

PMID- 20798757
TI  - Effects of growth hormone and insulin-like growth factor-1 on postoperative
      muscle and substrate metabolism.
AB  - This study explored if a combined supplementation of GH and IGF-1 had an additive
      effect on whole body nitrogen economy, energy, substrate and skeletal muscle
      metabolism following surgical trauma. Patients were randomized to controls (C; n
      = 10), to GH (0.15 IU/kg/injection) (GH; n = 7) or GH combined with IGF-1 (40
      mug/kg/injection) subcutaneously twice a day (GH-IGF-1; n = 9) together with
      standardized parenteral nutrition. Muscle amino acids, glutathione and the
      ribosomal pattern reflecting protein synthesis, and nitrogen balance were
      measured. GH- and GH-IGF-1 groups showed lower urea and higher plasma glucose
      concentrations. Energy expenditure increased in the GH-group. GH-IGF-1 prevented
      a decrease in muscle polyribosomes indicating a preserved muscle protein
      synthesis. In the GH group unaltered BCAA and AAA levels were seen in muscle
      indicating an unchanged protein breakdown, while the other groups showed
      increased muscle concentrations postoperatively. Without statistically difference
      GH marginally improved the nitrogen balance, in terms of higher values, and
      growth factors improved the nitrogen balance when the shift in urea was taken
      into account. To conclude, growth factors influences urea metabolism, protein
      degradation and protein synthesis. There was no clearcut additional effect when
      combining GH and IGF-1 but the study was probably underpowered to outrule this
      and effects on nitrogen balance.

PMID- 20798758
TI  - Chronic renal failure, cachexia, and ghrelin.
AB  - Protein energy wasting is frequently observed in patients with advanced chronic
      renal failure and end-stage renal disease. Anorexia and reduced food intake are
      critical contributing factors and negatively impact on patients' survival.
      Ghrelin is a prophagic peptide produced by the stomach and acting at the
      hypothalamic level to increase the activity of orexigenic neurons. In patients
      with chronic renal disease, plasma levels are increased as a likely effect of
      reduced renal clearance. Nevertheless, patients' food intake is significantly
      reduced, suggesting inflammation-mediated resistance of hypothalamic nuclei to
      peripheral signals. A number of forms of evidence show that ghrelin resistance
      could be overcome by the administration of exogenous ghrelin. Therefore, ghrelin
      has been proposed as a potential strategy to improve food intake in chronic renal
      failure patients with protein energy wasting. Preliminary data are encouraging
      although larger prospective clinical trials are needed to confirm the results and
      to identify those patients who are likely to benefit most from the administration
      of exogenous ghrelin.

PMID- 20798759
TI  - Role of BMI in the Association of the TCF7L2 rs7903146 Variant with Coronary
      Heart Disease: The Atherosclerosis Risk in Communities (ARIC) Study.
AB  - We examined the association of variation in the type 2 diabetes risk-conferring
      TCF7L2 gene with the risk of incident coronary heart disease (CHD) among the
      lean, overweight, and obese members of the Atherosclerosis Risk in Communities
      (ARIC) Study cohort. Cox proportional hazard regression analyses were performed
      using a general model, with the major homozygote as the reference category. For
      9,865 whites, a significant increase in the risk of CHD was seen only among lean
      ( BMI < 25 kg/m(2)) individuals homozygous for the T allele of the TCF7L2
      rs7903146 gene risk variant (hazard ratio 1.42; 95% CI 1.03,1.97; P = .01). No
      association was found among 3,631 blacks, regardless of BMI status. An attenuated
      hazard ratio was observed among the nondiabetic ARIC cohort members. This study
      suggests that body mass modifies the association of the TCF7L2 rs7903146 T allele
      with CHD risk.

PMID- 20798760
TI  - Differential toxicity of DNA adducts of mitomycin C.
AB  - The clinically used antitumor agent mitomycin C (MC) alkylates DNA upon reductive
      activation, forming six covalent DNA adducts in this process. This paper focuses
      on differential biological effects of individual adducts in various mammalian
      cell cultures, observed in the authors' laboratories. Evidence is reviewed that
      various adducts are capable of inducing different cell death pathways in cancer
      cells. This evidence is derived from a parallel study of MC and its derivatives
      2,7-diaminomitosene (2,7-DAM) which is the main metabolite of MC and forms two
      monoadducts with DNA, and decarbamoyl mitomycin C (DMC), which alkylates and
      crosslinks DNA, predominantly with a chirality opposite to that of the DNA
      adducts of MC. Specifically, 2,7-DAM is not cytotoxic and does not activate the
      p53 pathway while MC and DMC are cytotoxic and able to activate the p53 pathway.
      DMC is more cytotoxic than MC and can also kill p53-deficient cells by inducing
      degradation of Checkpoint 1 protein, which is not seen with MC treatment of the
      p53-deficient cells. This difference in the cell death pathways activated by the
      MC and DMC is attributed to differential signaling by the DNA adducts of DMC. We
      hypothesize that the different chirality of the adduct-to-DNA linkage has a
      modulating influence on the choice of pathway. Future studies will be directed to
      elucidate mechanisms of MC- and DMC-DNA adduct signaling in a structure-dependent
      context.

PMID- 20798761
TI  - Applying new research criteria for diagnosis of early Alzheimer's disease: sex
      and intelligence matter.
AB  - Alzheimer's disease (AD) can be diagnosed according to new research criteria
      proposed recently (Dubois et al., 2007). Diagnosis is made on grounds of episodic
      memory deficits and one pathological biomarker: cerebrospinal fluid (CSF) or
      structural/functional imaging. Goal was to investigate the dependence of episodic
      memory function on material (verbal, visuospatial), gender and premorbid
      intellectual ability (IQ). The new research criteria of AD were applied
      retrospectively using data of 68 patients (Mini-Mental-Status Examination, MMSE
      >/= 22) from a university memory clinic. Women with lower IQ performed worse on
      visuospatial episodic memory than women with higher IQ and men with the same IQ.
      Thus, women with lower IQ appear to be particularly vulnerable to visuospatial
      episodic memory deficits despite similar CSF tau values indicating a similar
      activity of the neurodegenerative process. Gender, premorbid IQ, and visuospatial
      material need to be considered in the assessment of episodic memory breakdown
      applying the newly proposed research criteria for the diagnosis of AD.

PMID- 20798762
TI  - Canine leishmaniasis in Brazil: serological follow-up of a dog population in an
      endemic area of american visceral leishmaniasis.
AB  - We performed a serological, clinical, and parasitological follow-up of a dog
      population in an endemic area of American Visceral Leishmaniasis estimated by
      indirect immunofluorescent assay (IFA) and western blot (WB). After twelve
      months, the results obtained from IFA demonstrated that 50% were seropositive and
      two serological profiles were observed: the first one ranging from 1/40 to 1/80
      and the second >/=1/160. By WB, it was observed that the same percentage and sera
      from positive dogs presented the recognition of the peptides of 29 and 32 kDa up
      to 8 months before IFA serum conversion. Among the positive dogs, all the sera
      from symptomatic ones with tissue parasitism recognized the peptide of 68.5 kDa.
      Our results suggest the need of modifications in the control measures regarding
      the elimination of the dogs. They also corroborate the high sensitivity and
      specificity of western blot in the diagnosis of canine leishmaniasis, suggesting
      the possibility of its association with IFA.

PMID- 20798763
TI  - Amyloid Beta annular protofibrils in cell processes and synapses accumulate with
      aging and Alzheimer-associated genetic modification.
AB  - Amyloid beta (Abeta) annular protofibrils (APFs) have been described where the
      structure is related to that of beta barrel pore-forming bacterial toxins and
      exhibits cellular toxicity. To investigate the relationship of Abeta APFs to
      disease and their ultrastructural localization in brain tissue, we conducted a
      pre-embedding immunoelectron microscopic study using anti-annular protofibril
      antiserum. We examined brain tissues of young- and old-aged amyloid precursor
      protein transgenic mice (APP23), neprilysin knockout APP23 mice, and
      nontransgenic littermates. alphaAPF-immunoreactions tended to be found (1) on
      plasma membranes and vesicles inside of cell processes, but not on amyloid
      fibrils, (2) with higher density due to aging, APP transgene, and neprilysin
      deficiency, and (3) with higher positive rate at synaptic compartments in aged
      APP23, especially in neprilysin knockout APP23 mice. These findings imply that
      APFs are distinct from amyloid fibrils, interact with biological membranes, and
      might be related to synaptic dysfunction in Alzheimer model mouse brains.

PMID- 20798764
TI  - Kung fu training improves physical fitness measures in overweight/obese
      adolescents: the "martial fitness" study.
AB  - Aim. To examine the efficacy of a six-month Kung Fu (KF) program on physical
      fitness in overweight/obese adolescents. Methods. Subjects were randomly assigned
      to the KF or sham exercise (Tai Chi, TC) control group. Physical measurements in
      cardiovascular fitness and muscle fitness occurred at baseline and after 6 months
      of training thrice weekly. Results. Twenty subjects were recruited. One subject
      was lost to follow-up, although overall compliance to the training sessions was
      46.7 +/- 27.8%. At follow-up, the cohort improved in absolute upper (P = .002)
      and lower (P = .04) body strength, and upper body muscle endurance (P = .02),
      without group differences. KF training resulted in significantly greater
      improvements in submaximal cardiovascular fitness (P = .03), lower body muscle
      endurance (P = .28; significant 95% CI: 0.37-2.49), and upper body muscle
      velocity (P = .03) relative to TC training. Conclusions. This short-term KF
      program improved submaximal cardiovascular fitness, lower body muscle endurance,
      and muscle velocity, in overweight/obese adolescents with very low baseline
      fitness.

PMID- 20798765
TI  - The effect of ingested macronutrients on postprandial ghrelin response: a
      critical review of existing literature data.
AB  - Ghrelin is a powerful orexigenic gut hormone with growth hormone releasing
      activity. It plays a pivotal role for long-term energy balance and short-term
      food intake. It is also recognized as a potent signal for meal initiation.
      Ghrelin levels rise sharply before feeding onset, and are strongly suppressed by
      food ingestion. Postprandial ghrelin response is totally macronutrient specific
      in normal weight subjects, but is rather independent of macronutrient composition
      in obese. In rodents and lean individuals, isoenergetic meals of different
      macronutrient content suppress ghrelin to a variable extent. Carbohydrate appears
      to be the most effective macronutrient for ghrelin suppression, because of its
      rapid absorption and insulin-secreting effect. Protein induces prolonged ghrelin
      suppression and is considered to be the most satiating macronutrient. Fat, on the
      other hand, exhibits rather weak and insufficient ghrelin-suppressing capacity.
      The principal mediators involved in meal-induced ghrelin regulation are glucose,
      insulin, gastrointestinal hormones released in the postabsorptive phase, vagal
      activity, gastric emptying rate, and postprandial alterations in intestinal
      osmolarity.

PMID- 20798766
TI  - Capture of a Transition State Using Molecular Dynamics: Creation of an
      Intercalation Site in dsDNA with Ethidium Cation.
AB  - The mechanism of intercalation and the ability of double stranded DNA (dsDNA) to
      accommodate a variety of ligands in this manner has been well studied. Proposed
      mechanistic steps along this pathway for the classical intercalator ethidium have
      been discussed in the literature. Some previous studies indicate that the
      creation of an intercalation site may occur spontaneously, with the energy for
      this interaction arising either from solvent collisions or soliton propagation
      along the helical axis. A subsequent 1D diffusional search by the ligand along
      the helical axis of the DNA will allow the ligand entry to this intercalation
      site from its external, electrostatically stabilized position. Other mechanistic
      studies show that ethidium cation participates in the creation of the site, as a
      ligand interacting closely with the external surface of the DNA can cause
      unfavorable steric interactions depending on the ligands' orientation, which are
      relaxed during the creation of an intercalation site. Briefly, such a site is
      created by the lengthening of the DNA molecule via bond rotation between the
      sugars and phosphates along the DNA backbone, causing an unwinding of the dsDNA
      itself and separation between the adjacent base pairs local to the position of
      the ligand, which becomes the intercalation site. Previous experimental
      measurements of this interaction measure the enthalpic cost of this part of the
      mechanism to be about -8 kcal/mol. This paper reports the observation, during a
      computational study, of the spontaneous opening of an intercalation site in
      response to the presence of a single ethidium cation molecule in an externally
      bound configuration. The concerted motions between this ligand and the host, a
      dsDNA decamer, are clear. The dsDNA decamer AGGATGCCTG was studied; the central
      ...GATG... site was the intercalation site.

PMID- 20798767
TI  - Consumption of Cross-Linked Resistant Starch (RS4(XL)) on Glucose and Insulin
      Responses in Humans.
AB  - Objective. The objective was to compare the postprandial glycemic and insulinemic
      responses to nutrition bars containing either cross-linked RS type 4 (RS4(XL)) or
      standard wheat starch in normoglycemic adults (n = 13; age = 27 +/- 5 years; BMI
      = 25 +/- 3 kg/m(2)). Methods. Volunteers completed three trials during which they
      consumed a glucose beverage (GLU), a puffed wheat control bar (PWB), and a bar
      containing cross-linked RS4 (RS4(XL)) matched for available carbohydrate content.
      Serial blood samples were collected over two hours and glucose and insulin
      concentrations were determined and the incremental area under the curve (iAUC)
      was calculated. Results. The RS4(XL) peak glucose and insulin concentrations were
      lower than the GLU and PWB (P < .05). The iAUC for glucose and insulin were lower
      following ingestion of RS4 compared with the GLU and PWB trials. Conclusions.
      These data illustrate, for the first time, that directly substituting standard
      starch with RS4(XL), while matched for available carbohydrates, attenuated
      postprandial glucose and insulin levels in humans. It remains to be determined
      whether this response was due to the dietary fiber and/or resistant starch
      aspects of the RS4(XL) bar.

PMID- 20798768
TI  - Patient Groups and the Construction of the Patient-Consumer in Britain: An
      Historical Overview.
AB  - This article presents an historical overview of the changing meaning of the
      patient-consumer, and specifically the role played by patient groups in
      constructing the patient as consumer. It is argued that patient groups were
      central to the formation of the patient-consumer, but as health consumerism was
      taken on by the state, they lost control of this figure. Competing understandings
      of what it meant to be a patient-consumer developed, a shift that raises further
      questions about the unity of claims made in the name of the patient-consumer.

PMID- 20798770
TI  - Postoperative cardiac arrest after heart surgery: does extracorporeal perfusion
      support a paradigm change in management?
AB  - Early institution of extracorporeal perfusion support (ECPS) may improve survival
      after cardiac arrest. Two patients sustained unexpected cardiac arrest in the
      Intensive Care Unit (ICU) following cardiac interventions. ECPS was initiated due
      to failure to restore hemodynamics after prolonged (over 60 minutes) advanced
      cardiac life support (ACLS) protocol-guided cardiopulmonary resuscitation.
      Despite relatively late institution of ECPS, both patients survived with
      preserved neurological function. This communication focuses on the utility of
      ECPS in the ICU as a part of resuscitative efforts.

PMID- 20798769
TI  - Neuroinflammation, microglia and implications for anti-inflammatory treatment in
      Alzheimer's disease.
AB  - Neuroinflammation has been implicated in the pathology of Alzheimer's disease
      (AD) for decades. Still it has not been fully understood when and how
      inflammation arises in the course of AD. Whether inflammation is an underling
      cause or a resulting condition in AD remains unresolved. Mounting evidence
      indicates that microglial activation contributes to neuronal damage in
      neurodegenerative diseases. However, also beneficial aspects of microglial
      activation have been identified. The purpose of this review is to highlight new
      insights into the detrimental and beneficial role of neuroinflammation in AD. It
      is our intention to focus on newer controversies in the field of microglia
      activation. Precisely, we want to shed light on whether neuroinflammation is
      associated to brain tissue damage and functional impairment or is there also a
      damage limiting activity. In regard to this, we discuss the limitations and the
      advantages of anti-inflammatory treatment options and identify what future
      implications might result from this underling neuroinflammation for AD therapy.

PMID- 20798771
TI  - Diagnostic methods for feline coronavirus: a review.
AB  - Feline coronaviruses (FCoVs) are found throughout the world. Infection with FCoV
      can result in a diverse range of signs from clinically inapparent infections to a
      highly fatal disease called feline infectious peritonitis (FIP). FIP is one of
      the most serious viral diseases of cats. While there is neither an effective
      vaccine, nor a curative treatment for FIP, a diagnostic protocol for FCoV would
      greatly assist in the management and control of the virus. Clinical findings in
      FIP are non-specific and not helpful in making a differential diagnosis.
      Haematological and biochemical abnormalities in FIP cases are also non-specific.
      The currently available serological tests have low specificity and sensitivity
      for detection of active infection and cross-react with FCoV strains of low
      pathogenicity, the feline enteric coronaviruses (FECV). Reverse transcriptase
      polymerase chain reaction (RT-PCR) has been used to detect FCoV and is rapid and
      sensitive, but results must be interpreted in the context of clinical findings.
      At present, a definitive diagnosis of FIP can be established only by
      histopathological examination of biopsies. This paper describes and compares
      diagnostic methods for FCoVs and includes a brief account of the virus biology,
      epidemiology, and pathogenesis.

PMID- 20798772
TI  - Technological innovations in surgical approach for thyroid cancer.
AB  - Over the last decade, surgeons have witnessed dramatic changes in surgical
      practice as a result of the introduction of new technological advancement. Some
      of these changes include refinement of techniques in thyroid cancer surgery. The
      development of various endoscopic thyroidectomy techniques, the addition of the
      da Vinci robot, and the use of operative adjuncts in thyroid surgery, such as
      intraoperative neuromonitoring and quick intraoperative parathyroid hormone, have
      made thyroid cancer surgery not only safer and better accepted by patients with
      thyroid cancer but also offer them more surgical treatment options.

PMID- 20798773
TI  - Geographic Distribution of Childbirth among Adolescents in Cameroon from 2003 to
      2005.
AB  - Objective. To determine the frequency and the trend of adolescents (10-19 years)
      in childbirth within a period of 3 years in referral maternity units in Cameroon.
      Method. Descriptive and retrospective study for a 3-year period (2003-2005) in
      referral maternity units headed by a qualified Obstetrician-Gynecologist. We
      analyzed the trend and geographic distribution of 8222 adolescent deliveries over
      3 years. Epi Info 3.5 software was used for data analysis. Chi square test for
      trend was used to assess the contribution of adolescent deliveries over years.
      The trend was considered significant if P < .05. Results. During the period of
      the study, there was a total of 8387 deliveries. We excluded 165 women because of
      lack of information about age. We therefore included a total of 8222 adolescent
      deliveries. Overall, the contribution of adolescents to deliveries ranged from
      6.87% to 26.51%, depending on the region with a national mean of 14.23%.
      Adolescents aged 16 or less contributed to 2.82% of deliveries while those aged
      from 17 to 19 contributed to 11.41%. The contribution of adolescents to
      deliveries decreased significantly over 3 years (P < .0001). Conclusion. The
      study underscores the importance of Public Health programs in strengthening
      maternity services for adolescents in Cameroon while taking into consideration
      geographic differences.

PMID- 20798774
TI  - Specificity of methylation assays in cancer research: a guideline for designing
      primers and probes.
AB  - DNA methylation is an epigenetic regulation mechanism of genomic function, and
      aberrant methylation pattern has been found to be a common event in many diseases
      and human cancers. A large number of cancer studies have been focused on
      identification of methylation changes as biomarkers (i.e., breast cancer).
      However, still clinical use of them is very limited because of lack of
      specificity and sensitivity for diagnostic test. This highlights the critical
      need for specific primer and probe design to avoid false-positive detection of
      methylation profiling. The guideline and online web tools that are introduced in
      this paper might help to perform a successful experiment and to develop specific
      diagnosis biomarkers by designing right primer pair and probe prior to
      experimental step.

PMID- 20798775
TI  - Small deletion at the 7q21.2 locus in a CCM family detected by real-time
      quantitative PCR.
AB  - Cerebral cavernous malformations (CCMs) represent a common autosomal dominant
      disorder that predisposes patients to haemorrhagic strokes and focal neurological
      signs. About 56% of the hereditary forms of CCMs have been so far associated with
      mutations in the KRIT1 (Krev Interaction Trapped 1) gene, located at 7q21.2 (CCM1
      locus). We described the complete loss of 7q21.2 locus encompassing the KRIT1
      gene and 4 flanking genes in a CCM family by using a dense set of 12
      microsatellite markers. The complete loss of the maternal copy of KRIT1 gene
      region was confirmed by Real-Time Quantitative Polymerase Chain Reaction (RT
      QPCR) and the same approach was used for expression analysis. Additional RT-QPCR
      analysis showed the extension of the deletion, for a total of 700 kb, to the
      adjacent downstream and upstream-located genes, MTERF, AKAP9, CYP51A1, as well as
      a partial loss of the ANKIB1 gene. Here we report the molecular characterization
      of an interstitial small genomic deletion of the 7q21.2 region in a CCMs affected
      family, encompassing the KRIT1 gene. Our findings confirm the loss of function
      mechanism for the already known CCM1 locus, without any evident involvement of
      the other deleted genes. Moreover, our investigations highlight the usefulness of
      the RT-QPCR to the molecular characterization of the breakpoints genomic
      deletions and to the identification of internal deleted genes involved in the
      human genetic diseases.

PMID- 20798776
TI  - Gene-gene interaction in maternal and perinatal research.

PMID- 20798778
TI  - Advances in muscle physiology and pathophysiology.

PMID- 20798777
TI  - Oral microencapsulated live Saccharomyces cerevisiae cells for use in renal
      failure uremia: preparation and in vivo analysis.
AB  - Orally administrable alginate-poly-L-lysine-alginate (APA) microcapsules
      containing live yeast cells was investigated for use in renal failure. At all
      times, yeast cells remain inside the microcapsules, which are then excreted in
      the stool. During their gastrointestinal passage, small molecules, like urea,
      diffuse into the yeast microcapsules where they are hydrolyzed. Orally
      administrating these microcapsules to uremic rats was found to decrease urea
      concentrations from 7.29 +/- 0.89 mmol/L to 6.12 +/- 0.90 mmol/L over a treatment
      period of eight weeks. After stopping the treatment, the urea concentrations
      increased back to uremic levels of 7.64 +/- 0.77 mmol/L. The analysis of
      creatinine concentrations averaged 39.19 +/- 4.33 micromol/L, 50.83 +/- 5.55
      micromol/L, and 50.28 +/- 7.10 micromol/L for the normal-control, uremic-control
      and uremic-treatment groups, respectively. While creatinine concentrations for
      both uremic-control and uremic-treatment groups did not differ among each other
      (P > .05), they were, however, significantly higher than those of the normal
      control group (P < .05). Uric acid concentrations averaged 80.08 +/- 26.49
      micromol/L, 99.92 +/- 26.55 micromol/L, and 86.49 +/- 28.42 micromol/L for the
      normal-control, uremic-control and uremic-treatment groups, respectively. There
      were no significant differences in both calcium and phosphate concentrations
      among all three groups (P > .05). The microbial populations of five tested types
      of bacteria were not substantially altered by the presence of the yeast APA
      encapsulated yeast (P > .05).

PMID- 20798779
TI  - Translation Requires Evidence: Does Cancer-Specific CGA Lead to Better Care and
      Outcomes?

PMID- 20798780
TI  - Increased Human Wildtype Tau Attenuates Axonal Transport Deficits Caused by Loss
      of APP in Mouse Models.
AB  - Amyloid precursor protein (APP) is implicated in axonal elongation, synaptic
      plasticity, and axonal transport. However, the role of APP on axonal transport in
      conjunction with the microtubule associated protein tau continues to be debated.
      Here we measured in vivo axonal transport in APP knockout mice with Manganese
      Enhanced MRI (MEMRI) to determine whether APP is necessary for maintaining normal
      axonal transport. We also tested how overexpression and mutations of tau affect
      axonal transport in the presence or absence of APP. In vivo axonal transport
      reduced significantly in the absence of functional APP. Overexpression of human
      wildtype tau maintained normal axonal transport and resulted in a transient
      compensation of axonal transport deficits in the absence of APP. Mutant R406Wtau
      in combination with the absence of APP compounded axonal transport deficits and
      these deficits persisted with age. These results indicate that APP is necessary
      for axonal transport, and overexpression of human wildtype tau can compensate for
      the absence of APP at an early age.

PMID- 20798781
TI  - The Reactive-Proactive Aggression Questionnaire: Differential Correlates of
      Reactive and Proactive Aggression in Adolescent Boys.
AB  - This study reports the development of the Reactive-Proactive Aggression
      Questionnaire (RPQ), and the differential correlates of these two forms of
      aggression. Antisocial, psychosocial and personality measures were obtained at
      ages 7 and 16 years in schoolboys, while the RPQ was administered to 334 of the
      boys at age 16 years. Confirmatory factor analysis indicated a significant fit
      for a two-factor proactive-reactive model that replicated from one independent
      subsample to another. Proactive aggression was uniquely characterized at age 7 by
      initiation of fights, strong-arm tactics, delinquency, poor school motivation,
      poor peer relationships, single-parent status, psychosocial adversity, substance
      abusing parents, and hyperactivity, and at age 16 by a psychopathic personality,
      blunted affect, delinquency, and serious violent offending. Reactive aggression
      was uniquely characterized at age 16 by impulsivity, hostility, social anxiety,
      lack of close friends, unusual perceptual experiences, and ideas of reference.
      Findings confirm and extend the differential correlates of proactive-reactive
      aggression, and demonstrate that this brief but reliable and valid self-report
      instrument can be used to assess proactive and reactive aggression in child and
      adolescent samples.

PMID- 20798782
TI  - Recent advances in the treatment of acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is a disorder with significant molecular and
      clinical heterogeneity. Although there have been clear advances in the
      identification of somatic genetic and epigenetic alterations present in the
      malignant cells of patients with AML, translating this knowledge into an
      integrated view with an impact on the clinical treatment of AML has been slower
      to evolve. Recent clinical advances in the treatment of AML include studies
      demonstrating the benefit of dose-intense daunorubicin therapy in induction
      chemotherapy for patients of any age. We also review use of the DNA
      methyltransferase inhibitor azacitidine for treatment of AML in elderly patients
      as well as a study of global patterns of DNA methylation in patients with AML.
      Lastly, we review a recent assessment of the role of allogeneic hematopoietic
      stem cell transplantation in AML in first complete remission.

PMID- 20798783
TI  - Targeted and Conditional Gene Expression Workshop, 8th International Conference
      on Zebrafish Development and Genetics.

PMID- 20798784
TI  - Increased cytochrome c correlates with poor survival in aggressive lymphoma.
AB  - Mitochondria are central to a variety of cellular processes, from metabolism to
      cell death. In this study, we demonstrated that an increase in the critical
      mitochondrial protein, cytochrome c, correlated with drug resistance in a cell
      culture model of aggressive lymphoma. Increased cytochrome c expression was also
      correlated with decreased survival in the aggressive diffuse large B-cell and
      mantle cell lymphomas, but not in the indolent follicular lymphoma. This suggests
      that an increased reliance on the mitochondria for energy allows tumor cells to
      be metabolic opportunists and contribute to tumor development and drug
      resistance.

PMID- 20798785
TI  - A DATA-DRIVEN APPROACH TO PRIOR EXTRACTION FOR SEGMENTATION OF LEFT VENTRICLE IN
      CARDIAC MR IMAGES.
AB  - In this paper, we propose a data-driven approach that extracts prior information
      for segmentation of the left ventricle in cardiac MR images of transplanted rat
      hearts. In our approach, probabilistic priors are generated from prominent
      features, i.e., corner points and scale-invariant edges, for both endo-and epi
      cardium segmentation. We adopt a level set formulation that integrates
      probabilistic priors with intensity, texture, and edge information for
      segmentation. Our experimental results show that with minimal user input,
      representative priors are correctly extracted from the data itself, and the
      proposed method is effective and robust for segmentation of the left ventricle
      myocardium even in images with very low contrast. More importantly, it avoids
      inter- and intra- observer variations and makes accurate quantitative analysis of
      low-quality cardiac MR images possible.

PMID- 20798786
TI  - An Open-Source Standard T-Wave Alternans Detector for Benchmarking.
AB  - We describe an open source algorithm suite for T-Wave Alternans (TWA) detection
      and quantification. The software consists of Matlab implementations of the widely
      used Spectral Method and Modified Moving Average with libraries to read both WFDB
      and ASCII data under windows and Linux. The software suite can run in both batch
      mode and with a provided graphical user interface to aid waveform exploration.
      Our software suite was calibrated using an open source TWA model, described in a
      partner paper [1] by Clifford and Sameni. For the PhysioNet/CinC Challenge 2008
      we obtained a score of 0.881 for the Spectral Method and 0.400 for the MMA
      method. However, our objective was not to provide the best TWA detector, but
      rather a basis for detailed discussion of algorithms.

PMID- 20798787
TI  - Destabilization of Bcr-Abl/Jak2 Network by a Jak2/Abl Kinase Inhibitor ON044580
      Overcomes Drug Resistance in Blast Crisis Chronic Myelogenous Leukemia (CML).
AB  - Bcr-Abl is the predominant therapeutic target in chronic myeloid leukemia (CML),
      and tyrosine kinase inhibitors (TKIs) that inhibit Bcr-Abl have been successful
      in treating CML. With progression of CML disease especially in blast crisis
      stage, cells from CML patients become resistant to imatinib mesylate (IM) and
      other TKIs, resulting in relapse. Because Bcr-Abl is known to drive multiple
      signaling pathways, the study of the regulation of stability of Bcr-Abl in IM
      resistant CML cells is a critical issue as a possible therapeutic strategy. Here,
      we report that a new dual-kinase chemical inhibitor, ON044580, induced apoptosis
      of Bcr-Abl+ IM-sensitive, IM-resistant cells, including the gatekeeper Bcr-Abl
      mutant, T315I, and also cells from blast crisis patients. In addition, IM
      resistant K562-R cells, cells from blast crisis CML patients, and all IM
      resistant cell lines tested had reduced ability to form colonies in soft agar in
      the presence of 0.5 uM ON044580. In in vitro kinase assays, ON044580 inhibited
      the recombinant Jak2 and Abl kinase activities when the respective Jak2 and Abl
      peptides were used as substrates. Incubation of the Bcr-Abl+ cells with ON044580
      rapidly reduced the levels of the Bcr-Abl protein and also reduced the expression
      of HSP90 and its client protein levels. Lysates of Bcr-Abl+ cell lines were found
      to contain a large signaling network complex composed of Bcr-Abl, Jak2, HSP90,
      and its client proteins as detected by a gel filtration column chromatography,
      which was rapidly disrupted by ON044580. Therefore, targeting Jak2 and Bcr-Abl
      kinases is an effective way to destabilize Bcr-Abl and its network complex, which
      leads to the onset of apoptosis in IM-sensitive and IM-resistant Bcr-Abl+ cells.
      This inhibitory strategy has potential to manage all types of drug-resistant CML
      cells, especially at the terminal blast crisis stage of CML, where TKIs are not
      clinically useful.

PMID- 20798789
TI  - Isolation and characterization of karlotoxin 1, a new amphipathic toxin from
      Karlodinium veneficum.
AB  - The karlotoxins (KmTxs) are a family of compounds produced by the dinoflagellate
      Karlodinium veneficum that cause membrane permeabilization. The structure of KmTx
      1, determined using extensive 2D NMR spectroscopy, is very similar to the
      amphidinols and related compounds, though KmTx 1 features unique structural
      modifications of the conserved core region. The structure of KmTx 1 differs from
      that reported for KmTx 2, the only other reported karlotoxin to date, in lacking
      chlorination at its terminal alkene and possessing a hydrophobic arm that is two
      carbons longer.

PMID- 20798790
TI  - Neurobehavioral outcomes in spina bifida: Processes versus outcomes.
AB  - We review neurobehavioral outcomes and interventions for children with spina
      bifida. Focusing on children with spina bifida myelomeningocele, we contrast
      historical views of outcomes based on comparisons across content domains (e.g.,
      language versus visual perceptual skills) with a view based on overarching
      processes that underlie strengths and weakness within content domains. Thus, we
      suggest that children with SBM have strengths when the skill involves the
      capacity to retrieve information from semantic memory and generate material that
      has been associatively linked or learned (associative processing) and general
      difficulties on tasks that require the construction or integration of a response
      (assembled processing). We use a hypothetical case to illustrate the differences
      in content domains versus general processes and also identify interventions that
      may be effective in addressing some of the cognitive and behavioral difficulties
      experienced variably by people with SBM. We extend these general principles to a
      discussion of variability in outcomes and use data from a large sample of
      children with spina bifida to illustrate the basis for this variability.

PMID- 20798791
TI  - A Method to Detect Differential Gene expression in Cross-Species Hybridization
      Experiments at Gene and Probe Level.
AB  - MOTIVATION: Whole genome microarrays are increasingly becoming the method of
      choice to study responses in model organisms to disease, stressors or other
      stimuli. However, whole genome sequences are available for only some model
      organisms, and there are still many species whose genome sequences are not yet
      available. Cross-species studies, where arrays developed for one species are used
      to study gene expression in a closely related species, have been used to address
      this gap, with some promising results. Current analytical methods have included
      filtration of some probes or genes that showed low hybridization activities. But
      consensus filtration schemes are still not available. RESULTS: A novel masking
      procedure is proposed based on currently available target species sequences to
      filter out probes and study a cross-species data set using this masking procedure
      and gene-set analysis. Gene-set analysis evaluates the association of some priori
      defined gene groups with a phenotype of interest. Two methods, Gene Set
      Enrichment Analysis (GSEA) and Test of Test Statistics (ToTS) were investigated.
      The results showed that masking procedure together with ToTS method worked well
      in our data set. The results from an alternative way to study cross-species
      hybridization experiments without masking are also presented. We hypothesize that
      the multi-probes structure of Affymetrix microarrays makes it possible to
      aggregate the effects of both well-hybridized and poorly-hybridized probes to
      study a group of genes. The principles of gene-set analysis were applied to the
      probe-level data instead of gene-level data. The results showed that ToTS can
      give valuable information and thus can be used as a powerful technique for
      analyzing cross-species hybridization experiments. AVAILABILITY: Software in the
      form of R code is available at http://anson.ucdavis.edu/~ychen/cross
      species.html.

PMID- 20798792
TI  - Public health teaching and research in the academy.

PMID- 20798793
TI  - Student participants in faculty educational research.

PMID- 20798794
TI  - Pharmacist licensure: time to step it up?

PMID- 20798795
TI  - Comparison of patients' expectations and experiences at traditional pharmacies
      and pharmacies offering enhanced advanced pharmacy practice experiences.
AB  - OBJECTIVES: To compare patients' expectations and experiences at pharmacies
      offering traditional APPE learning opportunities with those offering enhanced
      APPEs that incorporate pharmaceutical care activities. METHODS: A survey of
      anchored measures of patient satisfaction was conducted in 2 groups of APPE-
      affiliated community pharmacies: those participating in an enhanced APPE model
      versus those participating in the traditional model. The enhanced intervention
      included preceptor training, a comprehensive student orientation, and an extended
      experience at a single pharmacy rather than the traditional 2 x 4-week experience
      at different pharmacies. RESULTS: While patient expectations were similar in both
      traditional and enhanced APPE pharmacies, patients in enhanced pharmacies
      reported significantly higher in-store satisfaction and fewer service gaps.
      Additionally, satisfaction was significantly higher for patients who had received
      any form of consultation, from either pharmacist or students, than those
      reporting no consultations. CONCLUSION: Including provision of pharmaceutical
      care services as part of APPEs resulted in direct and measurable improvements in
      patient satisfaction.

PMID- 20798796
TI  - Nepalese pharmacy students' perceptions regarding mental disorders and pharmacy
      education.
AB  - OBJECTIVE: To determine Nepalese pharmacy students' perceptions of whether mental
      disorders impact performance in pharmacy school. METHOD: All first- and third
      year undergraduate pharmacy students (n=226) in Nepal were invited to complete a
      modified version of the Mental Illness Performance Scale. RESULTS: Among the 200
      respondents (response rate 88.5%), 14% reported that they had a mental disorder.
      The majority (92%) of third-year students agreed or strongly agreed that
      depression would interfere with a student's academic performance. Almost half of
      first-year students agreed or strongly agreed that alcohol or drug abuse would be
      grounds for both rejecting an applicant from pharmacy school (49%) and dismissal
      of a student from pharmacy school (46%). CONCLUSIONS: Students perceived a high
      level of academic impairment associated with mental disorders, but the majority
      did not perceive that mental disorders were grounds for dismissal from or
      rejection of entry to pharmacy school. Students' attitudes may discourage them
      from seeking help or providing mental health support to others.

PMID- 20798797
TI  - A blended learning approach to teaching basic pharmacokinetics and the
      significance of face-to-face interaction.
AB  - OBJECTIVE: To assess pharmacy students' attitudes towards a blended-learning
      pharmacokinetics course. DESIGN: Narrated visual presentations and animations
      that illustrated kinetic processes and guided students through the use of
      software programs used for calculations were created. Other learning techniques
      used included online self-assessment quizzes, practice problem sets, and weekly
      face-to-face problem-solving tutorials. ASSESSMENT: A precourse questionnaire to
      assess students' level of enthusiasm towards the blended-learning course and to
      solicit any concerns they had was administered at the beginning of the course. A
      postcourse questionnaire that included the same 4 Likert-scale items from the
      precourse questionnaire and follow-up open-ended questions was administered.
      Individual changes in level of enthusiasm were compared for individuals who
      completed both the precourse and postcourse questionnaire. Students' concerns
      about the blended method of learning had decreased postcourse while their
      enthusiasm for the benefits of blended learning had increased. CONCLUSION:
      Students' initial concerns about the blended learning experience were focused on
      their ability to communicate with the instructor about the online components, but
      shifted to their own time management skills at the end of the course. Face-to
      face interactions with each other and with the instructor were more highly rated
      than online interactions in this course.

PMID- 20798798
TI  - Global education implications of the foreign pharmacy graduate equivalency
      examination.
AB  - Although the Foreign Pharmacy Graduate Equivalency Examination (FPGEE) is not
      intended to measure educational outcomes or institutional effectiveness, it may
      be a reliable and valid criterion to assess the quality or success of
      international pharmacy programs. This comprehensive review describes the
      evolution and historical milestones of the FPGEE, along with trends in structure,
      administration, and passing rates, and the impact of country of origin on
      participant performance. Similarities between the FPGEE and the Pharmacy
      Curriculum Outcomes Assessment (PCOA) are also explored. This paper aims to
      provide a global prospective and insight for foreign academic institutions into
      parameters for evaluating their students' educational capabilities.

PMID- 20798799
TI  - Succession planning in US pharmacy schools.
AB  - The deans, associate and assistant deans, and department chairs of a college or
      school of pharmacy retain historic memories of the institution and share the
      responsibility for day-to-day operation, sustainability, and future planning.
      Between the anticipated retirement of baby boomers who are senior administrative
      faculty members and the steady increase in number of colleges and schools of
      pharmacy, the academy is facing a shortage of qualified successors. Succession
      planning involves planning for the effective transition of personnel in
      leadership positions within an organization. This paper describes the subject of
      succession planning at a sample population of AACP institutions by obtaining
      perspectives on the subject from the deans of these institutions via standardized
      interview instruments. The instruments were utilized with 15 deans; all interview
      data were blinded and analyzed using analyst triangulation. The majority of deans
      responded that some level of succession planning was desirable and even
      necessary; however, none claimed to have a formal succession planning structure
      in place at his or her home institution. Although widely accepted and well
      recognized in the corporate and military sectors, succession planning within
      pharmacy schools and colleges is neither universally documented nor implemented.
      Differences exist within the administrative structure of these non-academic and
      academic institutions that may preclude a uniform succession planning format.
      While the evidence presented suggests that succession planning is needed within
      the academy, a concerted effort must be made towards implementing its practice.

PMID- 20798800
TI  - Self-assessment in pharmacy and health science education and professional
      practice.
AB  - Self-assessment is an important skill necessary for continued development of a
      health care professional from student pharmacist throughout their professional
      career. This paper reviews the literature on student and practitioner self
      assessment and whether this skill can be improved upon. Although self-assessment
      appears to be a skill that can be improved, both students and professionals
      continue to have difficulty with accurate self-assessment. Experts' external
      assessment of students should remain the primary method of testing skills and
      knowledge until self-assessment strategies improve. While self-assessment is
      important to lifelong learning, external assessment is also important for
      practitioners' continuing professional development.

PMID- 20798801
TI  - Patient-oriented personality traits of first-year pharmacy students.
AB  - OBJECTIVE: To determine, using the Gordon Personal Profile-Inventory (GPP-I), if
      the personality traits of first-year pharmacy students match the traits required
      for patient-centered practice. METHODS: The GPP-I, which measures the personality
      traits of ascendency, responsibility, emotional stability, sociability,
      cautiousness, original thinking, personal relations, and vigor, was administered
      to incoming pharmacy students at the beginning of their first semester. RESULTS:
      The pharmacy school had attracted students with strong traits of original
      thinking, followed by personal relations, and vigor. The students, however, were
      limited in emotional stability and ascendency. CONCLUSION: The pharmacy
      profession needs to be more proactive in projecting the desired image and
      communicate its increasingly challenging and patient-oriented practice to attract
      individuals whose personalities are conducive to current practice models.

PMID- 20798802
TI  - Low vision simulator goggles in pharmacy education.
AB  - OBJECTIVE: To develop simulator goggles that produce disease-specific
      characteristics of selected low vision conditions for use in pharmacy education.
      METHODS: Individual sets of simulator goggles were developed for glaucoma,
      cataracts, macular degeneration, diabetic retinopathy, and retinitis pigmentosa.
      Students rated the presence and severity of disease-specific characteristics
      after wearing each pair of goggles while manipulating medication-related
      materials. RESULTS: One hundred students completed the study. Characteristic
      symptoms for each disease state were experienced at a moderate to severe level (p
      < 0.0001). Subjects indicated a high level of agreement among symptom ratings for
      each disease (Kendall's coefficient = 0.82). CONCLUSIONS: Low vision simulator
      goggles reliably produced the characteristics of selected conditions experienced
      in a medication management environment. Further studies are needed to identify
      suitable patient-centered learning activities using these goggles.

PMID- 20798803
TI  - Student measurement of blood pressure using a simulator arm compared with a live
      subject's arm.
AB  - OBJECTIVE: To compare accuracy of blood pressure measurements using a live
      subject and a simulator arm, and to determine students' preferences regarding
      measurement. METHODS: This was a crossover study comparing blood pressure
      measurements from a live subject and a simulator arm. Students completed an
      anonymous survey instrument defining opinions on ease of measurement. RESULTS:
      Fifty-seven students completed blood pressure measurements on live subjects while
      72 students completed blood pressure measurements using the simulator arm. There
      were no significant systematic differences between the 2 measurement techniques.
      Systolic blood pressure measurements from a live subject arm were less likely to
      be within 4 mm Hg compared with measurements of a simulator arm. Diastolic blood
      pressure measurements were not significantly different between the 2 techniques.
      CONCLUSIONS: Accuracy of student measurement of blood pressure using a simulator
      arm was similar to the accuracy with a live subject. There was no difference in
      students' preferences regarding measurement techniques.

PMID- 20798804
TI  - Graphic strategies for analyzing and interpreting curricular mapping data.
AB  - OBJECTIVE: To describe curricular mapping strategies used in analyzing and
      interpreting curricular mapping data and present findings on how these strategies
      were used to facilitate curricular development. DESIGN: Nova Southeastern
      University's doctor of pharmacy curriculum was mapped to the college's
      educational outcomes. The mapping process included development of educational
      outcomes followed by analysis of course material and semi-structured interviews
      with course faculty members. Data collected per course outcome included learning
      opportunities and assessment measures used. ASSESSMENT: Nearly 1,000 variables
      and 10,000 discrete rows of curricular data were collected. Graphic
      representations of curricular data were created using bar charts and stacked area
      graphs relating the learning opportunities to the educational outcomes. Graphs
      were used in the curricular evaluation and development processes to facilitate
      the identification of curricular holes, sequencing misalignments, learning
      opportunities, and assessment measures. CONCLUSION: Mapping strategies that use
      graphic representations of curricular data serve as effective diagnostic and
      curricular development tools.

PMID- 20798805
TI  - Development of a reliable, valid annual skills mastery assessment examination.
AB  - OBJECTIVE: To develop a methodology for a reliable, valid annual skills mastery
      assessment examination to provide formative student feedback, inform curricular
      review, and comply with the Accreditation Council for Pharmacy Education (ACPE)
      Standards 2007. DESIGN: A sample of program-level ability-based outcomes skills
      were chosen for the examination. Test items were written, underwent quality
      control, and were scored for level of difficulty. Versions of the examination for
      first-, second-, third-, and fourth-year pharmacy students were developed and
      administered, the results were analyzed, reliability and validity were evaluated,
      and reports were generated. Item-writing guidelines, quality control procedures,
      and examination production steps were codified to create a criterion-referenced
      examination. Students and faculty advisors received detailed score reports and
      results were used to guide student performance and stimulate a review of
      curricular outcomes. ASSESSMENT: Content, criterion, and construct validity were
      analyzed as defined in the literature for the intended use of this assessment
      tool. Data suggest the Annual Skills Mastery Assessment (ASMA) examination is
      both reliable and valid. Students and faculty members were surveyed regarding the
      usefulness of the examination. Results indicate general satisfaction with the
      assessment program. CONCLUSION: A reasonably reliable, reasonably valid multiple
      choice annual skills mastery assessment for selected outcomes statements
      providing formative feedback and informed curricular review was developed.

PMID- 20798806
TI  - Electronic reflective student portfolios to demonstrate achievement of ability
      based outcomes during advanced pharmacy practice experiences.
AB  - OBJECTIVES: To demonstrate achievement of ability-based outcomes through a
      structured review of electronic student portfolios in an advanced pharmacy
      practice experience (APPE) program. DESIGN: One hundred thirty-eight students
      produced electronic portfolios containing select work products from APPEs,
      including a self-assessment reflective essay that demonstrated achievement of
      course manual-specified ability-based outcomes. ASSESSMENT: Through portfolio
      submissions, all students demonstrated the achievement of ability-based outcomes
      for providing pharmaceutical care, evaluating the literature, and managing the
      medication use system with patient case reports most frequently submitted. The
      rubric review of self-reflective essays addressed student learning through APPEs
      and continuing professional development plans. CONCLUSION: The electronic
      portfolio with reflective essay proved to be a useful vehicle to demonstrate
      achievement of ability-based outcomes.

PMID- 20798807
TI  - First-year pharmacy students' self-assessment of communication skills and the
      impact of video review.
AB  - OBJECTIVES: To determine the ability of first-year students to self-assess
      communication skills and measure the impact of video review on students' self
      assessment. DESIGN: Students participated in a digital video-recorded, counseling
      simulation exercise and completed self-assessment before and after viewing their
      video. A faculty member evaluated the students using the same counseling
      assessment tool. ASSESSMENT: Correlation between the students' self-assessment
      scores and the faculty member's scores were poor (pre-video: r = 0.38, post
      video: r = 0.46). The largest portion of the students overestimated their skills
      in comparison to the faculty member's evaluations (47.1% pre-video and 67.9% post
      video). Those in the lowest quartile overestimated their skills, while those in
      the upper quartile underestimated their skills (pre-video). Video review brought
      about an increase in the self-assessment scores for nearly two-thirds (62.1%) of
      the students. CONCLUSION: First-year pharmacy students had difficulty self
      assessing, and video review increased their perception of skill achievement. A
      curriculum should include opportunities for students to develop self-assessment
      skills early in the program, and this should be reinforced throughout the
      curriculum.

PMID- 20798808
TI  - Anonymous peer assessment of medication management reviews.
AB  - OBJECTIVES: To investigate whether pharmacy students' anonymous peer assessment
      of a medication management review (MMR) was constructive, consistent with the
      feedback provided by an expert tutor, and enhanced the students' learning
      experience. DESIGN: Fourth-year undergraduate pharmacy students were randomly and
      anonymously assigned to a partner and participated in an online peer assessment
      of their partner's MMR. ASSESSMENT: An independent expert graded a randomly
      selected sample of the MMR's using a schedule developed for the study. A second
      expert evaluated the quality of the peer and expert feedback. Students also
      completed a questionnaire and participated in a focus group interview. Student
      peers gave significantly higher marks than an expert for the same MMR; however,
      no significant difference between the quality of written feedback between the
      students and expert was detected. The majority of students agreed that this
      activity was a useful learning experience. CONCLUSIONS: Anonymous peer assessment
      is an effective means of providing additional constructive feedback on student
      performance on the medication review process. Exposure to other students' work
      and the giving and receiving of peer feedback were perceived as valuable by
      students.

PMID- 20798809
TI  - Alignment of pharmacotherapy course assessments with course objectives.
AB  - OBJECTIVE: To determine whether instructor-prepared classroom examinations for
      pharmacotherapy courses were aligned with course goals and objectives. DESIGN:
      Assessment items from examinations in 2 pharmacotherapy courses were evaluated.
      Four categories of alignment (depth of knowledge, categorical concurrence, range
      of knowledge, and balance of representation) were used to match course
      assessments with objectives. ASSESSMENT: While assessments met the criteria for
      acceptable alignment, there were areas for improvement. Goals and objectives were
      unevenly assessed, with 1 goal aligning with 45% of all assessment items. The
      assessments covered all content categories and the range of knowledge established
      by the objectives, but objectives under specific goals were not evenly assessed.
      CONCLUSION: This alignment study provided quantitative data useful for review and
      revision of pharmacotherapy course objectives and assessments and demonstrated
      the usefulness of alignment assessment as a tool for continuous quality
      improvement.

PMID- 20798810
TI  - Extraversion predicts individual differences in face recognition.
AB  - In daily life, one of the most common social tasks we perform is to recognize
      faces. However, the relation between face recognition ability and social
      activities is largely unknown. Here we ask whether individuals with better social
      skills are also better at recognizing faces. We found that extraverts who have
      better social skills correctly recognized more faces than introverts. However,
      this advantage was absent when extraverts were asked to recognize non-social
      stimuli (e.g., flowers). In particular, the underlying facet that makes
      extraverts better face recognizers is the gregariousness facet that measures the
      degree of inter-personal interaction. In addition, the link between extraversion
      and face recognition ability was independent of general cognitive abilities.
      These findings provide the first evidence that links face recognition ability to
      our daily activity in social communication, supporting the hypothesis that
      extraverts are better at decoding social information than introverts.

PMID- 20798811
TI  - Gadkin: A novel link between endosomal vesicles and microtubule tracks.
AB  - Different types of endosomal vesicles show distinct distribution patterns within
      cells. While early endosomes can be found throughout the cell, recycling
      endosomal vesicles and tubules tend to cluster near the microtubule organizing
      center in the perinuclear region in most cell types. The molecular mechanisms
      underlying the steady-state distribution and dynamics of various types of
      endosomal vesicles has long remained enigmatic. However, during the past decade
      it has become evident that microtubule-based motor proteins of the kinesin family
      play a pivotal role in the positioning of endosomes. Early endosomes were shown
      to cluster in the perinuclear area in the absence of KIF16B,1 KIF3A is required
      for the steady-state distribution of late endosomes/lysosomes,2 and KIF13A
      directs M6PR-containing vesicles from the TGN to the plasma membrane3 to name
      only a few examples. In the case of Tf-containing recycling endosomes antibody
      injection experiments implicated kinesin-1, a heteromer comprised of KIF5 heavy
      and KLC light chains, as a motor for their transport towards the cell periphery.4
      Indeed, KIF5B knockdown experiments confirmed that kinesin-1 is necessary to
      maintain the peripheral pool of recycling endosomes.5 But how is kinesin-1 linked
      to endosomal vesicles? Work from our own laboratory has identified the AP-1
      binding protein Gadkin as a molecular link between AP-1-mediated traffic and
      kinesin-1-based transport along microtubules.5 This work as well as hypothetical
      models for kinesin-dependent endosomal membrane traffic will be discussed here.

PMID- 20798812
TI  - Do invertebrates have culture?
AB  - A recent paper in Current Biology1 showed for the first time that female
      invertebrates (Drosophila melanogaster) can perform mate choice copying. Here, we
      discuss how female mating preferences in this species may be transmitted
      culturally. If culture occurs in invertebrates, it may be a relatively ancient
      evolutionary process that may have contributed to the evolution of many different
      taxa. This would considerably broaden the taxonomic range of cultural processes
      and suggest the need to include cultural inheritance in all animals into the
      general theory of evolution.2-4.

PMID- 20798813
TI  - Emerging roles for tubulin folding cofactors at the centrosome.
AB  - Despite its fundamental role in centrosome biology, procentriole formation, both
      in the canonical and in the de novo replication pathways, remains poorly
      understood, and the molecular components that are involved in human cells are not
      well established. We found that one of the tubulin cofactors, TBCD, is localized
      at centrosomes and the midbody, and is required for spindle organization, cell
      abscission, centriole formation and ciliogenesis. Our studies have established a
      molecular link between the centriole and the midbody, demonstrating that this
      cofactor is also necessary for microtubule retraction during cell abscission.
      TBCD is the first centriolar protein identified that plays a role in the assembly
      of both "centriolar rosettes" during early ciliogenesis, and at the procentriole
      budding site by S/G(2), a discovery that directly implicates tubulin cofactors in
      the cell division, cell migration and cell signaling research fields.

PMID- 20798814
TI  - Heterokairy as an anti-predator strategy for parasitic species.
AB  - Heterokairy refers to plasticity in the timing of onset of developmental events
      at the level of an individual. When two developmental stages do not share the
      same ecological niche, referred to as 'ontogenetic niches', the control of the
      niche shift through a change in developmental timing can be advantageous for the
      individual (e.g., when mortality risk is different in the two niches).
      Heterokairy can arise either from plasticity in developmental rate (ontogenetic
      shift) or by a purely behavioral decision (behavioral shift). Parasitic species
      living inside of their hosts often inherit the predators of their hosts. To cope
      with the predation risk on their hosts, parasites and parasitoids show either
      host-manipulation abilities or either host-leaving strategies. Nevertheless,
      leaving the host should be associated with developmental costs, since the
      parasitic individuals are usually unable to parasitize another host. This process
      is thus related to the classical tradeoff between size and developmental time.
      Recent studies provided examples of behavioral heterokairy in invertebrates. The
      goal of this publication is to review and discuss recent results on developmental
      plasticity in parasitic species in an evolutionary perspective.

PMID- 20798815
TI  - Transduction of wound and herbivory signals in plastids.
AB  - Plastids are the central orchestrators of the early and late responses to
      wounding and herbivory in plants. This organelle houses some of the most
      important enzymes involved in the biogenesis of intra and extracellular signals
      that mediate defense responses against these stresses. Among these enzymes are
      the ones initiating the biosynthesis of oxylipins [e.g., jasmonic acid (JA) and
      C(6) volatiles], terpenoid volatiles and phenolic compounds, including both
      volatile [e.g., methylsalicylate (MeSA)] and non-volatile compounds [e.g.,
      salicylic acid (SA)]. Plastids also play a major role in orchestrating changes in
      primary metabolism during herbivory and thereby in the reallocation of carbon and
      nitrogen to different functions in response to herbivory. How the primary stress
      signals generated by mechanical damage and herbivory reach the plastid to
      activate the rapid synthesis of these signal molecules is at present largely
      unknown.

PMID- 20798816
TI  - A genomic glance at the components of the mRNA export machinery in Plasmodium
      falciparum.
AB  - Nuclear export of mRNAs is one of the steps critically important for gene
      expression and different steps of mRNA processing are linked to the export of the
      mRNA out of the nucleus. This coupling probably provides a quality control
      mechanism as well as a higher efficiency for the synthesis of mRNAs. The mRNA is
      synthesized in the nucleus and then exported to the cytoplasm through the nuclear
      pore complexes (NPCs), which are embedded in the nuclear envelope. The Mex67-Mtr2
      complex in yeast and its counterpart Tap-p15 in higher eukaryotes function as an
      mRNA exporter through the NPC. Some of the DEAD box proteins such as UAP56 and
      Dbp5 have been implicated in mRNA export also. In this report using the
      bioinformatics approach we have analyzed the components of the mRNA export
      machinery in Plasmodium falciparum and also highlighted the salient features of
      some of the components. Further detailed studies on various components of nuclear
      mRNA export in Plasmodium falciparum will be essential to understand this
      important pathway.

PMID- 20798817
TI  - The homeodomain transcription factor Ste12: Connecting fungal MAPK signalling to
      plant pathogenicity.
AB  - A conserved mitogen-activated protein kinase (MAPK) cascade orthologous to the
      mating/filamentation MAPK pathway in yeast is required for fungal pathogenicity
      on plants. One of the key targets of this signaling pathway is the homeodomain
      transcription factor Ste12. Mutational analysis of ste12 orthologues in a variety
      of plant pathogenic fungi suggests that Ste12 functions as a master regulator of
      invasive growth. In this mini-review we highlight recent progress in
      understanding the role of Ste12 in filamentous fungi and discuss future
      challenges of unravelling the mechanisms by which Ste12 controls fungal virulence
      downstream of the Pathogenicity MAPK cascade.

PMID- 20798818
TI  - Competition-colonization dynamics: An ecology approach to quasispecies dynamics
      and virulence evolution in RNA viruses.
AB  - A single and purified clone of foot-and-mouth disease virus diversified in cell
      culture into two subpopulations that were genetically distinct. The subpopulation
      with higher virulence was a minority and was suppressed by the dominant but less
      virulent one. These two populations follow the competitioncolonization dynamics
      described in ecology. Virulent viruses can be regarded as colonizers because they
      killed the cells faster and they spread faster. The attenuated subpopulation
      resembles competitors because of its higher replication efficiency in coinfected
      cells. Our results suggest a new model for the evolution of virulence which is
      based on interactions between components of the quasispecies. Competition between
      viral mutants takes place at two levels, intracellular competition and
      competition for new cells. The two strategies are subjected to densitydependent
      selection.

PMID- 20798819
TI  - Application of the heterochrony framework to the study of behavior and cognition.
AB  - Heterochrony, or the evolution of ontogeny, has been well studied in embryology
      and skeletal development, providing insight into morphological and genetic
      mechanisms of evolution.1-5 However, heterochronic studies of behavior and
      cognition lag behind in comparison. In a recent study we investigated the
      ontogeny of social behavior and cognition in humans' closest living relatives,
      chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). These two species are
      estimated to have had a chimpanzeelike common ancestor between 0.86 and 1.8
      mya.6,7 Bonobos have been argued to exhibit morphological indications of
      paedomorphism relative to chimpanzees, especially in the cranium, and to exhibit
      paedomorphic behavior as adults.6-11 We found that bonobos exhibit developmental
      delays relative to chimpanzees in several aspects of their social behavior and
      cognition. Here, we describe how placing these results in the framework of
      heterochrony contributes to understanding behavioral and cognitive differences
      between adults of these two species and to our knowledge of hominid evolution in
      general.

PMID- 20798820
TI  - Neurogranin and synaptic plasticity balance.
AB  - Learning-related modifications of synaptic transmission at CA1 hippocampal
      excitatory synapses are activity- and NMDA receptor (NMDAR)-dependent. While a
      postsynaptic increase in Ca(2+) is absolutely required for synaptic plasticity
      induction, the molecular mechanisms underlying the transduction of synaptic
      signals to postsynaptic changes are not clearly understood. In our recent study,
      we found that the postsynaptic calmodulin (CaM)-binding protein neurogranin (Ng)
      enhances synaptic strength in an activity- and NMDAR-dependent manner.
      Furthermore we have shown that Ng is not only required for the induction of long
      term potentiation (LTP), but its mediated synaptic potentiation also mimics and
      occludes LTP. Our results demonstrate that Ng plays an important role in the
      regulation of hippocampal synaptic plasticity and synaptic function. Here, we
      summarize our findings and further discuss their possible implications in aging
      related synaptic plasticity deficits.

PMID- 20798821
TI  - Probing novel GPCR interactions using a combination of FRET and TIRF.
AB  - Recent work on G-protein coupled receptors (GPCRs) has highlighted the importance
      of homo- and heterodimerization in all areas of GPCR function, including
      trafficking, signaling and desensitization. Novel GPCR dimers and even high-order
      oligomers are constantly being discovered. Advances in techniques such as
      fluorescent microscopy have improved our ability to detect these interactions. As
      GPCRs represent the largest class of transmembrane signaling molecules in
      biology, these new insights into their function could vastly improve our
      understanding of the complex physiological role GPCRs play in cellular signaling.
      Utilizing a combination of classic biochemical approaches and newer techniques
      such as fluorescence resonance energy transfer (FRET) and total internal
      reflection fluorescence microscopy (TIRF), we recently demonstrated a novel
      interaction between M(2) muscarinic receptors and GABA(B) receptors. In this
      addendum, we address technical aspects of combining FRET and TIRF to study GPCR
      interactions and further discuss the physiological implications of the M(2)
      GABA(B) heterodimer.

PMID- 20798822
TI  - SynDIG1 regulation of synaptic AMPA receptor targeting.
AB  - Excitatory synapses are composed of several specialized domains including the
      presynaptic bouton containing several hundred synaptic vesicles (svs), the
      presynaptic active zone where svs dock and fuse with the plasma membrane, and the
      juxtaposed postsynaptic density (psd) composed of an electron dense meshwork of
      proteins including nmda and ampa receptors, ion channels, and various signaling
      components. cell adhesion molecules (cams) extend across the synaptic cleft to
      stabilize this macromolecular complex. during development of the central nervous
      system (cns), certain cams also serve as inductive signals that trigger the
      establishment of pre- and postsynaptic specializations.1-4 Early events in
      synapse development include clustering of SVs to the active zone and NMDA
      receptors to the PSD, whereas later events include targeting of AMPA receptors
      and synaptic activity that might direct whether synapses will be stabilized,
      eliminated or strengthened. Regulating the number of AMPA receptors located at
      the PSD is a key mechanism underlying synaptic strength and plasticity implicated
      in learning and memory.5-10 Thus, a current avenue of investigation is the
      identification of interacting proteins that influence targeting of synaptic AMPA
      receptors. The discovery that the transmembrane protein stargazin controls
      synaptic AMPA-R targeting represented a major paradigm shift in the field.11 My
      colleagues and I recently reported the discovery of a novel type II transmembrane
      protein SynDIG1 (Synapse Differentiation Induced Gene I) that functions as a
      critical regulator of excitatory synapse development in dissociated rat
      hippocampal neurons.12 Specifically, knock-down of SynDIG1 in cultured neurons
      reduces AMPA receptor content at developing synapses by approximately 50% as
      determined by immunocytochemistry and electrophysiology.12 The magnitude of this
      effect matches that of TARPs and PSD-95 identifying SynDIG1 as a previously
      unknown central regulator of postsynaptic AMPA receptor targeting. In this
      addendum I further discuss the implications of these data.

PMID- 20798823
TI  - The natural selection of fidelity in social learning.
AB  - Social learning mechanisms are usually assumed to explain both the spread and the
      persistence of cultural behavior. In a recent article, we showed that the
      fidelity of social learning commonly found in transmission chain experiments is
      not high enough to explain cultural stability. Here we want to both enrich and
      qualify this conclusion by looking at the case of song transmission in song
      birds, which can be faithful to the point of being true replication. We argue
      that this high fidelity results from natural selection pressure on cognitive
      mechanisms. This observation strengthens our main argument. Social learning
      mechanisms are unlikely to be faithful enough to explain cultural stability
      because they are generally selected not for high fidelity but for generalization
      and adjustment to the individual's needs, capacities and situation.

PMID- 20798824
TI  - Cholesterol and synaptic vesicle exocytosis.
AB  - LIPIDS MAY AFFECT SYNAPTIC FUNCTION IN AT LEAST TWO WAYS: by acting as ligands
      for effector proteins [e.g., phosphatidylinositol (4,5) bisphosphate,
      diacylglycerol-mediated signaling] or by modifying the physicochemical properties
      and molecular organization of synaptic membranes. One that acts in the latter
      manner is cholesterol, an essential structural component of plasma membranes that
      is largely enriched in the membranes of synapses and synaptic vesicles, in which
      it may be involved in lipid-lipid and protein-lipid interactions. Cholesterol is
      an important constituent of the "membrane rafts" that may play a role in
      recruiting and organizing the specific proteins of the exocytic pathways.
      Furthermore, many synaptic proteins bind directly to cholesterol. The regulation
      of cholesterol and lipid levels may therefore influence the specific interactions
      and activity of synaptic proteins, and have a strong impact on synaptic
      functions.

PMID- 20798825
TI  - Scaffolding proteins and non-proliferative functions of ERK1/2.
AB  - Studies of ERK1/2 generally focus on the regulation of nuclear ERK1/2 function
      mainly related to proliferation, whereas less attention has been drawn to the
      role ERK1/2 plays in the cytosol. Scaffolding proteins for ERK1/2 have been shown
      to control the time point and also the intracellular location of ERK1/2
      activation. Hence, by concentrating ERK1/2 within subcellular compartments,
      scaffolding proteins restrict the substrate specificity of ERK1/2 and thus
      optimize the cell response for specific signal transduction programs in order to
      manipulate specific cellular functions. We have presented evidence that the F
      actin binding protein calponin represents a new type of ERK1/2 scaffold,
      controlling the activation of a subfraction of ERK1/2 which is connected solely
      to contractile and/or migratory events in a cell.

PMID- 20798826
TI  - Addiction-like behavior in Drosophila.
AB  - Alcohol abuse is a pervasive problem known to be influenced by genetic factors,
      yet our understanding of the mechanisms underlying alcohol addiction is far from
      complete. Drosophila melanogaster has been established as a model for studying
      the molecular mechanisms that mediate the acute and chronic effects of alcohol.
      However, the Drosophila model has not yet been extended to include more complex
      alcohol-related behaviors such as self-administration. We recently established a
      paradigm to characterize ethanol consumption and preference in flies. We
      demonstrated that flies prefer to consume ethanol-containing food over regular
      food, and this preference exhibits several features of alcohol addiction: flies
      increase ethanol consumption over time, they consume ethanol to pharmacologically
      relevant concentrations, they will overcome an aversive stimulus in order to
      consume ethanol, and they exhibit relapse after a period of ethanol deprivation.
      Thus, ethanol preference in flies provides a new model for studying important
      aspects of addiction and their underlying mechanisms. One mutant that displayed
      decreased ethanol preference, krasavietz, may represent a first step toward
      uncovering those mechanisms.

PMID- 20798827
TI  - Eusocial insects as superorganisms: Insights from metabolic theory.
AB  - We recently published a paper titled "Energetic Basis of Colonial Living in
      Social Insects" showing that basic features of whole colony physiology and life
      history follow virtually the same size-dependencies as unitary organisms when a
      colony's mass is the summed mass of individuals. We now suggest that these
      results are evidence, not only for the superorganism hypothesis, but also for
      colony level selection. In addition, we further examine the implications of these
      results for the metabolism and lifetime reproductive success of eusocial insect
      colonies. We conclude by discussing the mechanisms which may underlie the
      observed mass-dependence of survival, growth and reproduction in these colonies.

PMID- 20798828
TI  - A model for the biogenesis of turnip mosaic virus replication factories.
AB  - Nicotiana benthamiana plants were agroinfiltrated with an infectious clone of the
      Turnip mosaic virus (TuMV) that was engineered to tag replication vesicles with
      either GFP or mCherry fluorescent proteins. Punctuate vesicle structures were
      observed in the cytoplasm of infected cells corresponding to viral replication
      factories. The vesicles were highly motile and co-aligned with the
      microfilaments. Utilization of latrunculin B, an inhibitor of microfilament
      polymerization, reduced accumulation of the virus, suggesting that microfilaments
      are necessary during infection. To investigate biogenesis of the vesicles, leaves
      were infected simultaneously with two recombinant TuMV infectious clones, one
      that labeled vesicles in red and one that labeled them in green. We observed cell
      with green only and red only vesicles indicating a single viral genome origin. In
      some cases, vesicles exhibited sectors of green, red and yellow fluorescence were
      also observed, demonstrating that fusion among individual vesicles is possible.
      Based on those results we propose a model for the biogenesis of viral factory,
      where viral translation and replication are tightly coupled within virus-induced
      vesicles.

PMID- 20798829
TI  - Direct internalization of cell-surface BST-2/tetherin by the HIV-1 accessory
      protein Vpu.
AB  - The host transmembrane protein BST-2/tetherin is a powerful antiviral factor that
      blocks the production of enveloped viruses. The HIV-1 accessory protein Vpu
      inhibits the antiviral activity of BST-2; however, the degradation pathway by
      which Vpu downregulates BST-2 from the cell surface and the actual subcellular
      location where Vpu targets BST-2 for downregulation remain controversial. Whereas
      one study showed that Vpu acts on constitutively endocytosed BST-2, we recently
      reported that Vpu can internalize BST-2 from the cell surface. Because the
      evidence for this conclusion was derived from indirect results, we present direct
      evidence in this study using an antibody internalization assay with an
      endocytosis-defective mutant of BST-2. The internalization of the BST-2 protein
      into cells coexpressing wild-type Vpu was observed when the cells were
      preincubated with antibodies against BST-2 at 37 degrees C, but not at 4 degrees
      C, for 10 min. These results strongly support our previous finding that
      continuously expressed de novo BST-2 at the cell surface is internalized by
      functional Vpu protein.

PMID- 20798830
TI  - Multicolor bleach-rate imaging enlightens in vivo sterol transport.
AB  - Elucidation of in vivo cholesterol transport and its aberrations in
      cardiovascular diseases requires suitable model organisms and the development of
      appropriate monitoring technology. We recently presented a new approach to
      visualize transport of the intrinsically fluorescent sterol, dehydroergosterol
      (DHE) in the genetically tractable model organism Caenorhabditis elegans (C.
      elegans). DHE is structurally very similar to cholesterol and ergosterol, two
      sterols used by the sterol-auxotroph nematode. We developed a new computational
      method measuring fluorophore bleaching kinetics at every pixel position, which
      can be used as a fingerprint to distinguish rapidly bleaching DHE from slowly
      bleaching autofluorescence in the animals. Here, we introduce multicolor bleach
      rate sterol imaging. By this method, we demonstrate that some DHE is targeted to
      a population of basolateral recycling endosomes (RE) labelled with GFP-tagged RME
      1 (GFP-RME-1) in the intestine of both, wild-type nematodes and mutant animals
      lacking intestinal gut granules (glo1-mutants). DHE-enriched intestinal
      organelles of glo1-mutants were decorated with GFPrme8, a marker for early
      endosomes. No co-localization was found with a lysosomal marker, GFP-LMP1. Our
      new methods hold great promise for further studies on endosomal sterol transport
      in C. elegans.

PMID- 20798831
TI  - On classical and quantum error-correction in ciliate mate selection.
AB  - Ciliated protozoa sensing pheromones secreted from nonself mating types engage in
      preconjugal "courtship" dances and contacts. Using simulated "social" trials, I
      recently showed the heterotrich ciliate, Spirostomum ambiguum, can learn to
      advertise degrees of mating fitness to "suitors" and "rivals" when serially
      contracting or (ciliary) reversing at variable rates. Conspicuous consumers
      signal higher quality reproductive status by playing "harder-to-get" via
      metabolically wasteful avoidance displays that hinder the exchange of preconjugal
      touches between "courting" couples. Conversely, prudent savers conserve energy
      pending situations more favorable for conjugating a partner. These ciliates reply
      with lower avoidance frequencies, guaranteeing nearby conspecifics of being
      "easier-to-get". By deciding to switch from behavioral strategies signaling
      conspicuous consumption to those signaling prudent savings, fitter ciliates learn
      to altruistically sacrifice net payoffs and persuade suitors to participate in
      paired reproduction. Less fit ciliates, unable to sustain long periods of high
      response rates, switch their behavioral strategies of prudent savings to briefly
      emit conspicuous consumption and thus learn to opportunistically cheat superior
      rivals. Mating competency depends, in part, on the efficiency of heuristics
      formed from recursive strategy searches and use. Heuristics represent stored
      patterns of action which evolve into ordered computational networks supporting
      entire courting repertoires. As ciliates expand signaling skills over many
      trials, the connectivity between strategies strengthens from Hebbian-like
      learning, leading to faster decisions about the appropriateness of courting
      messages and replies. The best experts master signaling decisions at efficiencies
      comparable to finding target solutions from superposed states with Grover's
      quantum search algorithm. I here append these findings with a critique on the
      feasibility of serial behavioral strategies to perfect ciliate mate selection via
      classical repetition and quantum bit-flip error-correction codes that safeguard
      transmitted social information from noise and might be exploited for signal
      encryption.

PMID- 20798833
TI  - Shedding light on the role of photosynthesis in pathogen colonization and host
      defense.
AB  - The role of photosynthesis in plant defense is a fundamental question awaiting
      further molecular and physiological elucidation. To this end we investigated host
      responses to infection with the bacterial pathogen Xanthomonas axonopodis pv.
      citri, the pathogen responsible for citrus canker. This pathogen encodes a plant
      like natriuretic peptide (XacPNP) that is expressed specifically during the
      infection process and prevents deterioration of the physiological condition of
      the infected tissue. Proteomic assays of citrus leaves infected with a XacPNP
      deletion mutant (DeltaXacPNP) resulted in a major reduction in photosynthetic
      proteins such as Rubisco, Rubisco activase and ATP synthase as a compared with
      infection with wild type bacteria. In contrast, infiltration of citrus leaves
      with recombinant XacPNP caused an increase in these host proteins and a
      concomitant increase in photosynthetic efficiency as measured by chlorophyll
      fluorescence assays. Reversion of the reduction in photosynthetic efficiency in
      citrus leaves infected with DeltaXacPNP was achieved by the application of XacPNP
      or Citrus sinensis PNP lending support to a case of molecular mimicry. Finally,
      given that DeltaXacPNP infection is less successful than infection with the wild
      type, it appears that reducing photosynthesis is an effective plant defense
      mechanism against biotrophic pathogens.

PMID- 20798832
TI  - Vestibular deficits do not underlie looping behavior in achiasmatic fish.
AB  - Zebrafish belladonna (bel) mutants carry a mutation in the lhx2 gene that encodes
      a Lim domain homeobox transcription factor, leading to a defect in the
      retinotectal axon pathfinding. As a result, a large fraction of homozygous bel
      mutants is achiasmatic. Achiasmatic bel mutants display ocular motor
      instabilities, both reserved optokinetic response (OKR) and spontaneous eye
      oscillations, and an unstable swimming behavior, described as looping. All these
      unstable behaviors have been linked to the underlying optic nerve projection
      defect. Looping has been investigated under different visual stimuli and shown to
      be vision dependent and contrast sensitive. In addition, looping correlates
      perfectly with reversed OKR and the spontaneous oscillations of the eyes. Hence,
      it has been hypothesized that looping is a compensatory response to the
      perception of self-motion induced by the spontaneous eye oscillations. However,
      both ocular and postural instabilities could also be caused by a yet unidentified
      vestibular deficit. Here, we performed a preliminary test of the vestibular
      function in achiasmatic bel larval mutants in order to clarify the potential role
      of a vestibular deficit in looping. We found that the vestibular ocular reflex
      (VOR) is normally directed in both bel mutants and wild types and therefore
      exclude the possibility that nystagmus and looping in reverse to the rotating
      optokinetic drum can be attributed to an underlying vestibular deficit.

PMID- 20798834
TI  - Cellular machinery to fuse antimicrobial autophagosome with lysosome.
AB  - Autophagy is an intracellular bulk degradation/recycling system that turns over
      cellular constituents and also functions to degrade intracellular foreign
      microbial invaders by a process termed xenophagy (antimicrobial autophagy). We
      previously showed that intracellular group A Streptococcus (GAS) organisms are
      captured by xenophagosomes, then degraded following fusion with lysosomes. Very
      recently, we analyzed the molecular mechanism underlying xenophagosome/lysosome
      fusion and found that endocytic soluble N-ethylmaleimide-sensitive factor
      attachment protein receptors (SNAREs) were involved. Knockdown of the
      combinational SNARE proteins Vti1b and VAMP8 with siRNAs disturbed autophagic
      fusion with lysosomes, and cellular bactericidal efficiency was significantly
      diminished. Furthermore, knockdown of those SNAREs inhibited the fusion of
      canonical autophagosomes with lysosomes. In addition, important findings showed
      that Vti1b is derived from autophagic compartments, whereas VAMP8 originates from
      lysosomes. Together, these results strongly suggest that SNARE proteins Vti1b and
      VAMP8 mediate the fusion of antimicrobial and canonical autophagosomes with
      lysosomes, an essential event for autophagic degradation.

PMID- 20798835
TI  - Both nymphs and adults of the maize orange leafhopper induce galls on their host
      plant.
AB  - The maize orange leafhopper, Cicadulina bipunctata, is a multivoltine insect that
      induces galls on various plants of the Poaceae. A previous study revealed that
      galls produced by this leafhopper were induced by dose-dependent stimulation on
      distant leaves from the feeding site, probably by chemical(s) injected from
      adults during feeding. In this paper, we examined the gall-inducing ability of C.
      bipunctata nymphs. The degree of gall induction gradually increased depending on
      the number of feeding nymphs and there were no significant differences from the
      positive control (feeding by five male adults) when seedlings were exposed to
      five or more nymphs. These results indicate that both adults and nymphs of C.
      bipunctata have the ability to induce galls on their host plants, a unique
      feature among gallinducing insects. This feature may be related to the free
      living, multivoltine and polyphagous habits of C. bipunctata.

PMID- 20798836
TI  - Intracellular cryptococci suppress Fc-mediated cyclin D1 elevation.
AB  - Cryptococcus neoformans (Cn) is the only encapsulated fungal pathogen pathogenic
      to humans and macrophages play a vital role in the Cn infection pathway.
      Previously we documented that phagocytosis or crosslinking of FcgammaR on
      macrophage cell surface promoted macrophage cell cycle progression via the
      activation of MAPK pathway. However, we seldom observed sustained macrophage
      growth after they phagocytosed live Cn. In fact, many macrophages were finally
      observed to undergo apoptotic changes after phagocytosis of live Cn. Here we
      report that cyclin D1 elevation in macrophages promoted by phagocytosis was
      suppressed by intracellular Cn cells. This suggests a novel cytotoxic mechanism
      for host cells of intracellular cryptococci.

PMID- 20798839
TI  - Late Onset Postpartum Eclampsia: It is Really Never Too Late-A Case of Eclampsia
      8 Weeks after Delivery.
AB  - Introduction. Eclampsia is the combination of preeclampsia and seizures.
      Approximately one-half of all cases of eclampsia occur postpartum. Thereby late
      onset postpartum eclampsia is defined by its onset more than 48 hours after
      delivery. Summary of Case. We report a postpartum eclampsia occurring 8 weeks
      after delivery, which is the latest onset ever described. The course was
      complicated by an intracerebral hemorrhage (ICH). Conclusion. A late onset
      postpartum eclampsia even several weeks after delivery should be considered as
      possible diagnosis, since early treatment initiation with magnesium sulphate and
      antihypertensive medication prevents severe complications and reduces mortality.

PMID- 20798837
TI  - Plant DNA recombinases: a long way to go.
AB  - DNA homologous recombination is fundamental process by which two homologous DNA
      molecules exchange the genetic information for the generation of genetic
      diversity and maintain the genomic integrity. DNA recombinases, a special group
      of proteins bind to single stranded DNA (ssDNA) nonspecifically and search the
      double stranded DNA (dsDNA) molecule for a stretch of DNA that is homologous with
      the bound ssDNA. Recombinase A (RecA) has been well characterized at genetic,
      biochemical, as well as structural level from prokaryotes. Two homologues of RecA
      called Rad51 and Dmc1 have been detected in yeast and higher eukaryotes and are
      known to mediate the homologous recombination in eukaryotes. The biochemistry and
      mechanism of action of recombinase is important in understanding the process of
      homologous recombination. Even though considerable progress has been made in
      yeast and human recombinases, understanding of the plant recombination and
      recombinases is at nascent stage. Since crop plants are subjected to different
      breeding techniques, it is important to know the homologous recombination
      process. This paper focuses on the properties of eukaryotes recombinases and
      recent developments in the field of plant recombinases Dmc1 and Rad51.

PMID- 20798838
TI  - Recanalization therapies in acute ischemic stroke: pharmacological agents,
      devices, and combinations.
AB  - The primary aim of thrombolysis in acute ischemic stroke is recanalization of an
      occluded intracranial artery. Recanalization is an important predictor of stroke
      outcome as timely restoration of regional cerebral perfusion helps salvage
      threatened ischemic tissue. At present, intravenously administered tissue
      plasminogen activator (IV-TPA) remains the only FDA-approved therapeutic agent
      for the treatment of ischemic stroke within 3 hours of symptom onset. Recent
      studies have demonstrated safety as well as efficacy of IV-TPA even in an
      extended therapeutic window. However, the short therapeutic window, low rates of
      recanalization, and only modest benefits with IV-TPA have prompted a quest for
      alternative approaches to restore blood flow in an occluded artery in acute
      ischemic stroke. Although intra-arterial delivery of the thrombolytic agent seems
      effective, various logistic constraints limit its routine use and as yet no lytic
      agent have not received full regulatory approval for intra-arterial therapy.
      Mechanical devices and approaches can achieve higher rates of recanalization but
      their safety and efficacy still need to be established in larger clinical trials.
      The field of acute revascularization is rapidly evolving, and various
      combinations of pharmacologic agents, mechanical devices, and novel
      microbubble/ultrasound technologies are being tested in multiple clinical trials.

PMID- 20798840
TI  - Effectiveness of Thrombolytic Therapy in Acute Embolic Stroke due to Infective
      Endocarditis.
AB  - Objective. To identify the role of thrombolytic therapy in acute embolic stroke
      due to infective endocarditis. Design. Case report. Setting. University hospital.
      Patient. A 70-year-old male presented with acute onset aphasia and hemiparesis
      due to infective endocarditis. His head computerized tomographic scan revealed
      left parietal sulcal effacement. He was given intravenous tissue plasminogen
      activator with significant resolution of the neurologic deficits without
      complications. Main Outcome Measures. Physical examination, National Institute of
      Health Stroke Scale, radiologic examination results. Conclusions. Thrombolytic
      therapy in selected cases of stroke due to infective endocarditis manifesting as
      major neurologic deficits can be considered as an option after careful
      consideration of risks and benefits. The basis for such favorable response rests
      in the presence of fibrin as a major constituent of the vegetation. The risk of
      precipitating hemorrhage with thrombolytic therapy especially with large infarcts
      and mycotic aneurysms should be weighed against the benefits of averting a major
      neurologic deficit.

PMID- 20798842
TI  - Lower body positive pressure application with an antigravity suit in acute
      carotid occlusion.
AB  - The challenge in acute stroke is still to reperfuse as early as possible the
      ischemic territory. Since fibrinolytic therapies have a limited window with
      potential risk of bleeding, having a nonpharmacologic mean to recruit vessels in
      area surrounding necrosis might be useful. We propose here to use antigravity
      suit inflated at "venous" pressure levels to shift blood towards thoracic and
      brain territories. We report two cases of spectacular clinical recovery after
      acute carotid occlusion.

PMID- 20798843
TI  - To know or not to know: ethical issues related to early diagnosis of Alzheimer's
      disease.
AB  - In Alzheimer's disease (AD), pathological processes start in the brain long
      before clinical dementia. Biomarkers reflecting brain alterations may therefore
      indicate disease at an early stage, enabling early diagnosis. This raises several
      ethical questions and the potential benefits of early diagnosis must be weighted
      against possible disadvantages. Currently, there are few strong arguments
      favouring early diagnosis, due to the lack of disease modifying therapy. Also,
      available diagnostic methods risk erroneous classifications, with potentially
      grave consequences. However, a possible benefit of early diagnosis even without
      disease modifying therapy is that it may enable early decision making when
      patients still have full decision competence, avoiding problems of hypothetical
      consents. It may also help identifying patients with cognitive dysfunction
      secondary to other diseases that may be responsive to treatment already today.

PMID- 20798841
TI  - Quasi-Static Ultrasound Elastography.
AB  - Elastography is a new imaging modality where elastic tissue parameters related to
      the structural organization of normal and pathological tissues are imaged. Basic
      principles underlying the quasi-static elastography concept and principles are
      addressed. The rationale for elastographic imaging is reinforced using data on
      elastic properties of normal and abnormal soft tissues. The several orders of
      magnitude difference between the elastic modulus of normal and abnormal tissues
      which is the primary contrast mechanism in elastographic imaging underlines the
      probability of success with this imaging modality. Recent advances enabling the
      clinical practice of elastographic imaging in real-time on clinical ultrasound
      systems is also discussed.In quasi-static elastography, radiofrequency echo
      signals acquired before and after a small (about 1%) of applied deformation are
      correlated to estimate tissue displacements. Local tissue displacement vector
      estimates between small segments of the pre- and post-deformation signals are
      estimated and the corresponding strain distribution imaged. Elastographic imaging
      techniques are based on the hypothesis that soft tissues deform more than stiffer
      tissue, and these differences can be quantified in images of the tissue strain
      tensor or the Young's modulus.Clinical applications of quasi-static elastography
      have mushroomed over the last decade, with the most commonly imaged areas being
      the breast, prostate, thyroid, cardiac, treatment monitoring of ablation
      procedures and vascular imaging applications.

PMID- 20798844
TI  - Validation of a novel physical activity assessment device in morbidly obese
      females.
AB  - Assessment of physical activity in morbidly obese subjects is important
      especially in bariatric surgery. We examined the validity of Intelligent Device
      for Energy Expenditure and Activity (IDEEA) for measuring physical activity and
      sedentary behavior in morbidly obese women. Activity types, gait counts, and
      speed detected by the IDEEA monitor were compared to those reported by an
      observer. The IDEEA monitor detected activity types and gait counts with
      relatively high accuracy, although slightly lower in extremely obese women than
      in normal weight controls. The IDEEA monitor accurately estimated gait speeds in
      both groups. Since gait speed predicts energy expenditure more accurately than
      gait counts, it is of greater clinical relevance. Reliability of the IDEEA
      monitor was excellent. The IDEEA monitor is a valid instrument for measuring
      physical activity and sedentary behavior in extremely obese women, and therefore
      has potential applications in bariatric surgery both in preoperative evaluation
      and long-term follow-up.

PMID- 20798845
TI  - Intereleukin-10 promoter polymorphism in mild cognitive impairment and in its
      clinical evolution.
AB  - Specific proinflammatory alleles are associated with higher risk of Alzheimer
      disease (AD) in different onset age. The homozygosis for the A allele of -1082
      polymorphism (G/A) of interleukin-10 (IL-10) promotes a higher risk of AD and
      reduced IL-10 generation in peripheral cells after amyloid stimulation. In this
      paper we analysed genotype and allele frequencies of this polymorphism in 138
      subjects with mild cognitive impairment (MCI) diagnosed, respectively, as
      amnestic (a-MCI) and multiple impaired cognitive domains (mcd-MCI). The genotype
      frequencies were similar in a-MCI and AD subjects, whereas in mcd-MCI comparable
      to controls (AA genotype: 50% in a-MCI, 49.2% in AD, 28.7% in mcd-MCI and 31.8%
      in controls). Consequently, both allele and genotype distributions were
      significantly different between a-MCI and mcd-MCI (allele: P = .02, genotype: P <
      .05). These results support the theory that polymorphisms of cytokine genes can
      affect neurodegeneration and its clinical progression. IL-10 may partly explain
      the conversion of a-MCI to AD or be a genetic marker of susceptibility.

PMID- 20798847
TI  - Thrombin-Binding Aptamer Quadruplex Formation: AFM and Voltammetric
      Characterization.
AB  - The adsorption and the redox behaviour of thrombin-binding aptamer (TBA) and
      extended TBA (eTBA) were studied using atomic force microscopy and voltammetry at
      highly oriented pyrolytic graphite and glassy carbon. The different adsorption
      patterns and degree of surface coverage were correlated with the sequence base
      composition, presence/absence of K(+), and voltammetric behaviour of TBA and
      eTBA. In the presence of K(+), only a few single-stranded sequences present
      adsorption, while the majority of the molecules forms stable and rigid
      quadruplexes with no adsorption. Both TBA and eTBA are oxidized and the only
      anodic peak corresponds to guanine oxidation. Upon addition of K(+) ions, TBA and
      eTBA fold into a quadruplex, causing the decrease of guanine oxidation peak and
      occurrence of a new peak at a higher potential due to the oxidation of G
      quartets. The higher oxidation potential of G-quartets is due to the greater
      difficulty of electron transfer from the inside of the quadruplex to the
      electrode surface than electron transfer from the more flexible single strands.

PMID- 20798848
TI  - Selective Incision of the alpha-N-Methyl-Formamidopyrimidine Anomer by
      Escherichia coli Endonuclease IV.
AB  - Formamidopyrimidines (Fapy) lesions result from ring opening of the imidazole
      portion of purines. Fapy lesions can isomerize from the natural beta-anomeric
      stereochemistry to the alpha-configuration. We have unambiguously demonstrated
      that the alpha-methyl-Fapy-dG (MeFapy-dG) lesion is a substrate for Escherichia
      coli Endonuclease IV (Endo IV). Treatment of a MeFapy-dG-containing 24 mer duplex
      with Endo IV resulted in 36-40% incision. The catalytic efficiency of the
      incision was comparable to that of alpha-dG in the same duplex sequence. The
      alpha- and beta-MeFapy-dG anomers equilibrate to ~21 : 79 ratio over ~3 days.
      Related studies with a duplex containing the alpha-Fapy-dG lesion derived from
      aflatoxin B(1) epoxide (alpha-AFB-Fapy-dG) showed only low levels of incision. It
      is hypothesized that the steric bulk of the aflatoxin moiety interferes with the
      binding of the substrate to Endo IV and the incision chemistry.

PMID- 20798849
TI  - Update on ghrelin.

PMID- 20798850
TI  - Does Preoperative Weight Change Predict Postoperative Weight Loss after
      Laparoscopic Roux-en-Y Gastric Bypass in the Short Term?
AB  - Background. Many institutions mandate preoperative weight loss prior to bariatric
      surgery. This study examines the correlation between preoperative weight change
      and postoperative success following laparoscopic Roux-en-Y gastric bypass.
      Methods. We retrospectively studied the correlation between change in BMI before
      surgery and change in BMI postoperatively, using linear regression analyses and
      one-way ANOVA, in 256 consecutive gastric bypass patients with 1-year followup.
      Results. Of 256 patients, 125 lost weight preoperatively (mean -1.7% BMI), while
      131 maintained or gained weight (mean +1.2% BMI). Postoperatively, there was no
      significant difference in percent BMI loss between the two groups (34.6% and
      34.5%). The percent change in BMI preoperatively did not predict postoperative
      BMI change after 1 year (P = n.s.). Conclusions. Our study did not show any
      correlation between preoperative weight change and postoperative weight loss
      after Roux-en-Y gastric bypass. Therefore, we do not believe that potential
      patients should be denied bariatric surgery on the basis of their inability to
      lose weight preoperatively.

PMID- 20798851
TI  - Evaluating the role of life events and sustaining conditions in weight loss
      maintenance.
AB  - Background. Recent qualitative research indicates that life events can enhance
      behaviour change maintenance. if a number of sustaining conditions are met. This
      study aimed to quantitatively test this theory in the context of weight loss
      maintenance. Method. Based upon their weight histories participants were
      classified as either successful (n = 431) or unsuccessful (n = 592) dieters and
      all completed questionnaires relating to life events, choice, the function of
      eating and exercise and the model of their weight problem. Findings. Successful
      dieters reported a higher number of life events than unsuccessful dieters
      particularly for events such as "clothes did not fit me", "doctor's
      recommendation" and "reached my heaviest weight". Successful participants also
      indicated reduced choice over their previous unhealthy diet, more choice over
      their exercise behaviours and more benefits from the new healthy behaviours. They
      were also less likely to attribute their previous increased weight to any medical
      and psychological factors. This was accompanied by a belief about the
      effectiveness of behavioural solutions to their weight problem. Discussion. Life
      events can promote behaviour change for some individuals. This change is
      facilitated by a reduction in choice and disruption of function over the
      unhealthy behaviours, and a belief that behavioural solutions will be effective.

PMID- 20798852
TI  - Confounding factors influencing amyloid Beta concentration in cerebrospinal
      fluid.
AB  - Background. Patients afflicted with Alzheimer's disease (AD) exhibit a decrease
      in the cerebrospinal fluid (CSF) concentration of the 42 amino acid form of beta
      amyloid (Abeta(42)). However, a high discrepancy between different centers in
      measured Abeta(42) levels reduces the utility of this biomarker as a diagnostic
      tool and in monitoring the effect of disease modifying drugs. Preanalytical and
      analytical confounding factors were examined with respect to their effect on the
      measured Abeta(42) level. Methods. Aliquots of CSF samples were either treated
      differently prior to Abeta(42) measurement or analyzed using different
      commercially available xMAP or ELISA assays. Results. Confounding factors
      affecting CSF Abeta(42) levels were storage in different types of test tubes,
      dilution with detergent-containing buffer, plasma contamination, heat treatment,
      and the origin of the immunoassays used for quantification. Conclusion. In order
      to conduct multicenter studies, a standardized protocol to minimize preanalytical
      and analytical confounding factors is warranted.

PMID- 20798853
TI  - Pre-Steady-State Kinetic Analysis of Truncated and Full-Length Saccharomyces
      cerevisiae DNA Polymerase Eta.
AB  - Understanding polymerase fidelity is an important objective towards ascertaining
      the overall stability of an organism's genome. Saccharomyces cerevisiae DNA
      polymerase eta (yPoleta), a Y-family DNA polymerase, is known to efficiently
      bypass DNA lesions (e.g., pyrimidine dimers) in vivo. Using pre-steady-state
      kinetic methods, we examined both full-length and a truncated version of yPoleta
      which contains only the polymerase domain. In the absence of yPoleta's C-terminal
      residues 514-632, the DNA binding affinity was weakened by 2-fold and the base
      substitution fidelity dropped by 3-fold. Thus, the C-terminus of yPoleta may
      interact with DNA and slightly alter the conformation of the polymerase domain
      during catalysis. In general, yPoleta discriminated between a correct and
      incorrect nucleotide more during the incorporation step (50-fold on average) than
      the ground-state binding step (18-fold on average). Blunt-end additions of dATP
      or pyrene nucleotide 5'-triphosphate revealed the importance of base stacking
      during the binding of incorrect incoming nucleotides.

PMID- 20798854
TI  - Evaluation of human telomeric g-quadruplexes: the influence of overhanging
      sequences on quadruplex stability and folding.
AB  - To date, various G-quadruplex structures have been reported in human telomeric
      sequences. Human telomeric repeats can form many topological structures depending
      on conditions and on base modification; parallel, antiparallel, and hybrid forms.
      The effect of salts and some specific ligands on conformational switches between
      different conformers is known, but the influence of protruding sequences has
      rarely been discussed. In this paper, we analyze different quadruplex-forming
      oligomers derived from human telomeric sequences which contain 3'- and 5'
      protruding nucleotides, not usually associated with the G-quadruplex motif. The
      study was performed using electrophoresis, CD, and UV spectroscopies. The major
      findings are (i) protruding nucleotides destabilize the G-quadruplex structure,
      and (ii) overhanging sequences influence the folding of the quadruplex.

PMID- 20798856
TI  - Methods to Enhance Verbal Communication between Individuals with Alzheimer's
      Disease and Their Formal and Informal Caregivers: A Systematic Review.
AB  - Alzheimer's disease is the leading cause of dementia in older adults. Although
      memory problems are the most characteristic symptom of this disorder, many
      individuals also experience progressive problems with communication. This
      systematic review investigates the effectiveness of methods to improve the verbal
      communication of individuals with Alzheimer's disease with their caregivers. The
      following databases were reviewed: PsychINFO, CINAHL, EMBASE, MEDLINE, REHABDATA,
      and COMDIS. The inclusion criteria were: (i) experimentally based studies, (ii)
      quantitative results, (iii) intervention aimed at improving verbal communication
      of the affected individual with a caregiver, and (iv) at least 50% of the sample
      having a confirmed diagnosis of Alzheimer's disease. A total of 13 studies met
      all of the inclusion criteria. One technique emerged as potentially effective:
      the use of memory aids combined with specific caregiver training programs. The
      strength of this evidence was restricted by methodological limitations of the
      studies. Both adoption of and further research on these interventions are
      recommended.

PMID- 20798855
TI  - Ghrelin cells in the gastrointestinal tract.
AB  - Ghrelin is 28-amino-acid peptide that was discovered from the rat and human
      stomach in 1999. Since the discovery of ghrelin, various functions of ghrelin,
      including growth hormone release, feeding behavior, glucose metabolism, memory,
      and also antidepressant effects, have been studied. It has also been reported
      that ghrelin in the gastrointestinal tract has an important physiological effect
      on gastric acid secretion and gastrointestinal motility. Ghrelin has a unique
      structure that is modified by O-acylation with n-octanoic acid at third serine
      residues, and this modification enzyme has recently been identified and named
      ghrelin O-acyl transferase (GOAT). Ghrelin is considered to be a gut-brain
      peptide and is abundantly produced from endocrine cells in the gastrointestinal
      mucosa. In the gastrointestinal tract, ghrelin cells are most abundant in the
      stomach and are localized in gastric mucosal layers. Ghrelin cells are also
      widely distributed throughout the gastrointestinal tract. In addition, abundance
      of ghrelin cells in the gastric mucosa is evolutionally conserved from mammals to
      lower vertebrates, indicating that gastric ghrelin plays important roles for
      fundamental physiological functions. Ghrelin cells in the gastrointestinal tract
      are a major source of circulating plasma ghrelin, and thus understanding the
      physiology of these cells would reveal the biological significance of ghrelin.

PMID- 20798857
TI  - Executive Function Skills of 6 to 8 Year Olds: Brain and Behavioral Evidence and
      Implications for School Achievement.
AB  - Academic and social success in school has been linked to children's self
      regulation. This study investigated the assessment of the executive function (EF)
      component of self-regulation using a low-cost, easily administered measure to
      determine whether scores obtained from the behavioral task would agree with those
      obtained using a laboratory-based neuropsychological measure of EF skills. The
      sample included 74 children (37 females; M = 86.2 months) who participated in two
      assessments of working memory and inhibitory control: Knock-Tap (NEPSY: Korkman,
      Kirk, and Kemp, 1998), and participation in event-related potential (ERP) testing
      that included the Directional Stroop Test (Davidson, Cruess, Diamond, O'Craven, &
      Savoy, 1999). Three main findings emerged. First, children grouped as high versus
      low performing on the NEPSY Knock-Tap Task were found to performed differently on
      the more difficult conditions of the DST (the Incongruent and Mixed Conditions),
      suggesting that the Knock-Tap Task as a low-cost and easy to administer
      assessment of EF skills may be one way for teachers to identify students with
      poor inhibitory control skills. Second, children's performance on the DST was
      strongly related to their ERP responses, adding to evidence that differences in
      behavioral performance on the DST as a measure of EF skills reflect corresponding
      differences in brain processing. Finally, differences in brain processing on the
      DST task also were found when the children were grouped based on Knock-Tap
      performance. Simple screening procedures can enable teachers to identify children
      whose distractibility, inattentiveness, or poor attention spans may interfere
      with classroom learning.

PMID- 20798858
TI  - Long-term effects of metformin and lifestyle modification on nonalcoholic Fatty
      liver disease obese adolescents.
AB  - Objective. To assess the long-term effects of metformin in combination with
      lifestyle intervention and its association between insulin levels and the degree
      of steatosis at ultrasonography (US) in obese adolescents. Methods. Thirty-five
      postpubertal obese boys were randomized into two groups: one receiving metformin
      in combination with a multidisciplinary lifestyle intervention versus a placebo
      group, which also received the same intervention. The visceral, subcutaneous fat
      and degree of steatosis were measured by ultrasonography. Fasting blood samples
      were collected to analyze glucose, insulin, insulin resistance, and
      aminotransferases. Repeated ANOVA measures were used to compare changes over time
      and between groups, and Spearman's correlations were used to identify an
      association between insulin and the degree of steatosis at US. Results. There was
      a positive correlation between the degree of steatosis at US with insulin
      concentrations and HOMA-IR. Long-term therapy plus metformin significantly
      reduced body weight, body mass index, insulin, HOMA-IR, and visceral fat.
      Conclusions. Metformin was more effective than the placebo in improving clinical
      parameters associated with obesity and steatosis.

PMID- 20798859
TI  - Overeating Behavior and Striatal Dopamine with 6-[F]-Fluoro-L-m-Tyrosine PET.
AB  - Eating behavior may be affected by dopamine synthesis capacity. In this study, 6
      [(18)F]-fluoro-L-m-tyrosine (FMT) positron emission tomography (PET) uptake in
      striatal subregions was correlated with BMI (kg/m(2)) and an estimate of the
      frequency of prior weight loss attempts in 15 healthy subjects. BMI was
      negatively correlated with FMT uptake in the dorsal caudate. Although the
      association between BMI and FMT uptake in the dorsal caudate was not significant
      upon correction for age and sex, the association fell within the range of a
      statistical trend. Weight loss attempts divided by years trying was also
      negatively correlated with FMT uptake in the dorsal putamen (P = .05). These
      results suggest an association between low dorsal striatal presynaptic dopamine
      synthesis capacity and overeating behavior.

PMID- 20798846
TI  - Integrating GHS into the Ghrelin System.
AB  - Oligopeptide derivatives of metenkephalin were found to stimulate growth-hormone
      (GH) release directly by pituitary somatotrope cells in vitro in 1977. Members of
      this class of peptides and nonpeptidyl mimetics are referred to as GH
      secretagogues (GHSs). A specific guanosine triphosphatate-binding protein
      associated heptahelical transmembrane receptor for GHS was cloned in 1996. An
      endogenous ligand for the GHS receptor, acylghrelin, was identified in 1999.
      Expression of ghrelin and homonymous receptor occurs in the brain, pituitary
      gland, stomach, endothelium/vascular smooth muscle, pancreas, placenta,
      intestine, heart, bone, and other tissues. Principal actions of this peptidergic
      system include stimulation of GH release via combined hypothalamopituitary
      mechanisms, orexigenesis (appetitive enhancement), insulinostasis (inhibition of
      insulin secretion), cardiovascular effects (decreased mean arterial pressure and
      vasodilation), stimulation of gastric motility and acid secretion, adipogenesis
      with repression of fat oxidation, and antiapoptosis (antagonism of endothelial,
      neuronal, and cardiomyocyte death). The array of known and proposed interactions
      of ghrelin with key metabolic signals makes ghrelin and its receptor prime
      targets for drug development.

PMID- 20798860
TI  - Hierarchical formation of fibrillar and lamellar self-assemblies from guanosine
      based motifs.
AB  - Here we investigate the supramolecular polymerizations of two lipophilic
      guanosine derivatives in chloroform by light scattering technique and TEM
      experiments. The obtained data reveal the presence of several levels of
      organization due to the hierarchical self-assembly of the guanosine units in
      ribbons that in turn aggregate in fibrillar or lamellar soft structures. The
      elucidation of these structures furnishes an explanation to the physical
      behaviour of guanosine units which display organogelator properties.

PMID- 20798861
TI  - Psychological Impact of a "Health-at-Every-Size" Intervention on Weight
      Preoccupied Overweight/Obese Women.
AB  - The aim of the present study was to assess the impact of a "Health-at-every-size"
      (HAES) intervention on psychological variables and body weight the weight
      preoccupied overweight/obese women. Those women were randomized into three groups
      (1) HAES, (2) social support (SS), (3) waiting-list (WL), and were tested at
      baseline, post-treatment and six-month and one-year follow-ups. All participants
      presented significant psychological improvement no matter if they received the
      HAES intervention or not. However, even if during the intervention, the three
      groups showed improvements, during the follow up, the HAES group continued to
      improve while the other groups did not, even sometimes experiencing some
      deterioration. Furthermore, in the HAES group only, participant's weight
      maintenance 12 months after the intervention was related to their psychological
      improvement (quality of life, body dissatisfaction, and binge eating) during the
      intervention. Thus, even if, in the short-term, our study did not show
      distinctive effects of the HAES intervention compared to SS and WL on all
      variables, in the long-term, HAES group seemed to present a different trajectory
      as psychological variables and body weight are maintained or continue to improve,
      which was not the case in other groups. These differential long-term effects
      still need to be documented and further empirically demonstrated.

PMID- 20798862
TI  - Regulation of HuR by DNA Damage Response Kinases.
AB  - As many DNA-damaging conditions repress transcription, posttranscriptional
      processes critically influence gene expression during the genotoxic stress
      response. The RNA-binding protein HuR robustly influences gene expression
      following DNA damage. HuR function is controlled in two principal ways: (1) by
      mobilizing HuR from the nucleus to the cytoplasm, where it modulates the
      stability and translation of target mRNAs and (2) by altering its association
      with target mRNAs. Here, we review evidence that two main effectors of ataxia
      telangiectasia-mutated/ATM- and Rad3-related (ATM/ATR), the checkpoint kinases
      Chk1 and Chk2, jointly influence HuR function. Chk1 affects HuR localization by
      phosphorylating (hence inactivating) Cdk1, a kinase that phosphorylates HuR and
      thereby blocks HuR's cytoplasmic export. Chk2 modulates HuR binding to target
      mRNAs by phosphorylating HuR's RNA-recognition motifs (RRM1 and RRM2). We discuss
      how HuR phosphorylation by kinases including Chk1/Cdk1 and Chk2 impacts upon gene
      expression patterns, cell proliferation, and survival following genotoxic injury.

PMID- 20798863
TI  - An obesity dietary quality index predicts abdominal obesity in women: potential
      opportunity for new prevention and treatment paradigms.
AB  - Background. Links between dietary quality and abdominal obesity are poorly
      understood. Objective. To examine the association between an obesity-specific
      dietary quality index and abdominal obesity risk in women. Methods. Over 12
      years, we followed 288 Framingham Offspring/Spouse Study women, aged 30-69 years,
      without metabolic syndrome risk factors, cardiovascular disease, cancer, or
      diabetes at baseline. An 11-nutrient obesity-specific dietary quality index was
      derived using mean ranks of nutrient intakes from 3-day dietary records.
      Abdominal obesity (waist circumference >88 cm) was assessed during follow-up.
      Results. Using multiple logistic regression, women with poorer dietary quality
      were more likely to develop abdominal obesity compared to those with higher
      dietary quality (OR 1.87; 95% CI, 1.01, 3.47; P for trend = .048) independent of
      age, physical activity, smoking, and menopausal status. Conclusions. An obesity
      specific dietary quality index predicted abdominal obesity in women, suggesting
      targets for dietary quality assessment, intervention, and treatment to address
      abdominal adiposity.

PMID- 20798864
TI  - Metformin Improves Insulin Signaling in Obese Rats via Reduced IKKbeta Action in
      a Fiber-Type Specific Manner.
AB  - Metformin is a widely used insulin-sensitizing drug, though its mechanisms are
      not fully understood. Metformin has been shown to activate AMPK in skeletal
      muscle; however, its effects on the inhibitor of kappaB kinasebeta (IKKbeta) in
      this same tissue are unknown. The aim of this study was to (1) determine the
      ability of metformin to attenuate IKKbeta action, (2) determine whether changes
      in AMPK activity are associated with changes in IKKbeta action in skeletal
      muscle, and (3) examine whether changes in AMPK and IKKbeta function are
      consistent with improved insulin signaling. Lean and obese male Zuckers received
      either vehicle or metformin by oral gavage daily for four weeks (four groups of
      eight). Proteins were measured in white gastrocnemius (WG), red gastrocnemius
      (RG), and soleus. AMPK phosphorylation increased (P < .05) in WG in both lean
      (57%) and obese (106%), and this was supported by an increase in phospho-ACC in
      WG. Further, metformin increased IkappaBalpha levels in both WG (150%) and RG
      (67%) of obese rats, indicative of reduced IKKbeta activity (P < .05), and was
      associated with reduced IRS1-pSer(307) (30%) in the WG of obese rats (P < .02).
      From these data we conclude that metformin treatment appears to exert an
      inhibitory influence on skeletal muscle IKKbeta activity, as evidenced by
      elevated IkappaBalpha levels and reduced IRS1-Ser(307) phosphorylation in a fiber
      type specific manner.

PMID- 20798866
TI  - Biliary innate immunity: function and modulation.
AB  - Biliary innate immunity is involved in the pathogenesis of cholangiopathies in
      patients with primary biliary cirrhosis (PBC) and biliary atresia. Biliary
      epithelial cells possess an innate immune system consisting of the Toll-like
      receptor (TLR) family and recognize pathogen-associated molecular patterns
      (PAMPs). Tolerance to bacterial PAMPs such as lipopolysaccharides is also
      important to maintain homeostasis in the biliary tree, but tolerance to double
      stranded RNA (dsRNA) is not found. In PBC, CD4-positive Th17 cells characterized
      by the secretion of IL-17 are implicated in the chronic inflammation of bile
      ducts and the presence of Th17 cells around bile ducts is causally associated
      with the biliary innate immune responses to PAMPs. Moreover, a negative regulator
      of intracellular TLR signaling, peroxisome proliferator-activated receptor-gamma
      (PPARgamma), is involved in the pathogenesis of cholangitis. Immunosuppression
      using PPARgamma ligands may help to attenuate the bile duct damage in PBC
      patients. In biliary atresia characterized by a progressive, inflammatory, and
      sclerosing cholangiopathy, dsRNA viruses are speculated to be an etiological
      agent and to directly induce enhanced biliary apoptosis via the expression of
      tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Moreover, the
      epithelial-mesenchymal transition (EMT) of biliary epithelial cells is also
      evoked by the biliary innate immune response to dsRNA.

PMID- 20798865
TI  - Molecular and therapeutic potential and toxicity of valproic acid.
AB  - Valproic acid (VPA), a branched short-chain fatty acid, is widely used as an
      antiepileptic drug and a mood stabilizer. Antiepileptic properties have been
      attributed to inhibition of Gamma Amino Butyrate (GABA) transaminobutyrate and of
      ion channels. VPA was recently classified among the Histone Deacetylase
      Inhibitors, acting directly at the level of gene transcription by inhibiting
      histone deacetylation and making transcription sites more accessible. VPA is a
      widely used drug, particularly for children suffering from epilepsy. Due to the
      increasing number of clinical trials involving VPA, and interesting results
      obtained, this molecule will be implicated in an increasing number of therapies.
      However side effects of VPA are substantially described in the literature whereas
      they are poorly discussed in articles focusing on its therapeutic use. This paper
      aims to give an overview of the different clinical-trials involving VPA and its
      side effects encountered during treatment as well as its molecular properties.

PMID- 20798867
TI  - Tumor-Stromal Interactions Influence Radiation Sensitivity in Epithelial- versus
      Mesenchymal-Like Prostate Cancer Cells.
AB  - HS-27a human bone stromal cells, in 2D or 3D coultures, induced cellular
      plasticity in human prostate cancer ARCaP(E) and ARCaP(M) cells in an EMT model.
      Cocultured ARCaP(E) or ARCaP(M) cells with HS-27a, developed increased colony
      forming capacity and growth advantage, with ARCaP(E) exhibiting the most
      significant increases in presence of bone or prostate stroma cells. Prostate (Pt
      N or Pt-C) or bone (HS-27a) stromal cells induced significant resistance to
      radiation treatment in ARCaP(E) cells compared to ARCaP(M) cells. However
      pretreatment with anti-E-cadherin antibody (SHEP8-7) or anti-alpha v integrin
      blocking antibody (CNT095) significantly decreased stromal cell-induced radiation
      resistance in both ARCaP(E)- and ARCaP(M)-cocultured cells. Taken together the
      data suggest that mesenchymal-like cancer cells reverting to epithelial-like
      cells in the bone microenvironment through interaction with bone marrow stromal
      cells and reexpress E-cadherin. These cell adhesion molecules such as E-cadherin
      and integrin alpha v in cancer cells induce cell survival signals and mediate
      resistance to cancer treatments such as radiation.

PMID- 20798868
TI  - Evaluation of erythrocytes, platelets, and serum iron profile in dogs with
      chronic enteropathy.
AB  - The aim of this study is to evaluate iron status, erythrocyte, and platelet
      modifications in dogs with chronic enteropathy (CE). Dogs were grouped as food
      responsive diarrhea (FRD, n = 11), antibiotic-responsive diarrhea (ARD, n = 5),
      and steroid-responsive diarrhea (SRD, n = 6) relating to therapeutic-response.
      Clinical and haematological findings, evidence of gastrointestinal blood loss,
      and iron metabolism were evaluated before and after treatment. A mild normocytic
      or microcytic anemia and thrombocytosis were identified, respectively in 18.0%
      and 31.8% of CE dogs. No significant differences between pre- and posttreatment
      of hematocrit, haemoglobin, and mean corpuscular volume, platelet count and mean
      platelet volume were found. Statistical analysis pointed out significant
      differences between pre- and posttreatment in serum iron (P < .03) and
      unsaturated iron binding capacity (UIBC) (P < .01). No significant correlations
      were found between these parameters and canine Inflammatory Bowel Disease
      activity index and pattern of CE as well.

PMID- 20798869
TI  - Evaluation of mercury exposure reduction through a fish consumption advisory
      program for Anishinaabe tribal members in Northern Wisconsin, Michigan, and
      Minnesota.
AB  - The Great Lakes Indian Fish and Wildlife Commission has an extensive program to
      inform Anishinaabe tribal members from northern Wisconsin, Michigan, and
      Minnesota who harvest and consume walleye about the health risks of consuming
      these fish, and to encourage harvest and consumption practices that reduce
      exposure to MeHg. We report here the results of a probabilistic analysis of
      exposure to methyl mercury (MeHg) among tribal members who consume walleye. The
      model predicts that the potential for greatest exposures to MeHg occur among
      women of child-bearing age and children who consume large walleye from lakes that
      contain heavily contaminated (MeHg concentration >0.5 mg/kg) fish. The analysis
      allows GLIFWC to evaluate, focus, and fine-tune its initiatives to protect the
      health of tribal members in ways that result in exposure and risk reduction for
      tribal harvesters, women of child-bearing age, and children, while maintaining
      important tribal lifeways, which include the harvest and consumption of walleye.

PMID- 20798870
TI  - Hysterectomy-current methods and alternatives for benign indications.
AB  - Hysterectomy is the commonest gynecologic operation performed not only for
      malignant disease but also for many benign conditions such as fibroids,
      endometrial hyperplasia, adenomyosis, uterine prolapse, dysfunctional uterine
      bleeding, and cervical intraepithelial neoplasia. There are many approaches to
      hysterectomy for benign disease: abdominal hysterectomy, vaginal hysterectomy,
      laparoscopic assisted vaginal hysterectomy (LAVH) where a vaginal hysterectomy is
      assisted by laparoscopic procedures that do not include uterine artery ligation,
      total laparoscopic hysterectomy (TLH) where the laparoscopic procedures include
      uterine artery ligation, and subtotal laparoscopic hysterectomy (STLH) where
      there is no vaginal component and the uterine body is removed using a morcelator.
      In the last decades, many new techniques, alternative to hysterectomy with
      conservation of the uterus have been developed. They use modern technologies and
      their results are promising and in many cases comparable with hysterectomy. This
      paper is a review of all the existing hysterectomy techniques and the alternative
      methods for benign indications.

PMID- 20798872
TI  - Tetrahydrocannabinol (Delta 9-THC) Treatment in Chronic Central Neuropathic Pain
      and Fibromyalgia Patients: Results of a Multicenter Survey.
AB  - Central neuropathic pain is difficult to treat, but delta 9-Tetrahydrocannabinol
      (delta 9-THC) may be a promising therapeutic agent. We administered in 172
      patients on average 7.5 mg delta 9-THC over 7 months. Of these, 48 patients
      prematurely withdrew due to side effects, insufficient analgesia, or expense of
      therapy. Thus, 124 patients were assessed retrospectively in a multicenter
      telephone survey. Reported changes in pain intensity, recorded on a numeric
      rating scale (NRS), Pain Disability Index (PDI), Medical Outcomes Short-Form (SF
      12), Quality of Life Impairment by Pain (QLIP), Hospital Anxiety Depression Scale
      (HADS), and amount of concomitant pain medication were recorded. Psychometric
      parameters (PDI, SF-12, QLIP, HADS) and pain intensity improved significantly
      during delta 9-THC treatment. Opioid doses were reduced and patients perceived
      THC therapy as effective with tolerable side effects. About 25% of the patients,
      however, did not tolerate the treatment. Therapy success and tolerance can be
      assessed by a transient delta 9-THC titration and its maintained administration
      for several weeks. The present survey demonstrates its ameliorating potential for
      the treatment of chronic pain in central neuropathy and fibromyalgia. A
      supplemental delta 9-THC treatment as part of a broader pain management plan
      therefore may represent a promising coanalgesic therapeutic option.

PMID- 20798871
TI  - Nanofibers offer alternative ways to the treatment of skin infections.
AB  - Injury to the skin causes a breach in the protective layer surrounding the body.
      Many pathogens are resistant to antibiotics, rendering conventional treatment
      less effective. This led to the use of alternative antimicrobial compounds, such
      as silver ions, in skin treatment. In this review nanofibers, and the
      incorporation of natural antimicrobial compounds in these scaffolds, are
      discussed as an alternative way to control skin infections. Electrospinning as a
      technique to prepare nanofibers is discussed. The possibility of using these
      structures as drug delivery systems is investigated.

PMID- 20798873
TI  - Trial designs likely to meet valid long-term Alzheimer's disease progression
      effects: learning from the past, preparing for the future.
AB  - The International Society for CNS Clinical Trials and Methodology (ISCTM) held
      its 4th Annual Autumn Conference in Toronto, Ontario, October 6-7, 2008. The
      purpose of the present report is to provide an overview of one of the sessions at
      the conference which focused on the designs and methodologies to be applied in
      clinical trials of new treatments for Alzheimer's disease (AD) with purported
      "disease-modifying" effects. The session began with a discussion of how
      neuroimaging has been applied in multiple sclerosis clinical trials (another
      condition for which disease modification claims have been achieved). The next two
      lectures provided a pharmaceutical industry perspective on some of the specific
      challenges and possible solutions for designing trials to measure disease
      progression and/or modification. The final lecture provided an academic viewpoint
      and the closing discussion included additional academic and regulatory
      perspectives on trial designs, methodologies, and statistical issues relevant to
      the disease modification concept.

PMID- 20798874
TI  - Fatal Outcome of Disseminated Strongyloidiasis despite Detectable Plasma and
      Cerebrospinal Levels of Orally Administered Ivermectin.
AB  - Strongyloides stercoralis affects over 100 million people worldwide. Those people
      most susceptible to infection are those with an immunocompromising condition,
      such as cancer or human immunodeficiency virus (HIV). Local disease may spread
      throughout the body of the host, causing a condition termed disseminated
      strongyloidiasis. Standard treatment for Strongyloides stercoralis infection is
      oral ivermectin. We describe a patient with chronic lymphocytic leukemia
      diagnosed with disseminated strongyloidiasis two weeks after initial
      presentation. After repeated dosing of oral ivermectin with no clinical response,
      serum and cerebral spinal fluid (CSF) concentrations of ivermectin were measured
      to assess absorption. The peak serum concentration of 49.3 ng/mL correlated with
      a CSF concentration of 0.14 ng/mL. Despite these concentrations, the patient
      eventually succumbed to multi-system organ failure. We discuss the reasons for
      treatment failure and explore the utility of measuring ivermectin concentrations.

PMID- 20798875
TI  - Comparative evaluation of whole body and hepatic insulin resistance using indices
      from oral glucose tolerance test in morbidly obese subjects with nonalcoholic
      Fatty liver disease.
AB  - Nonalcoholic Fatty Liver Disease (NAFLD) is the hepatic manifestation of
      metabolic syndrome and is a marker of Insulin Resistance (IR). Euglycemic
      hyperinsulinemic clamp is the gold standard for measuring whole body IR (hepatic
      + peripheral IR). However, it is an invasive and expensive procedure. Homeostasis
      Model Assessment Index for Insulin Sensitivity (HOMA-IS), Quantitative Insulin
      Sensitivity Check Index (QUICKI) for hepatic IR and Insulin Sensitivity Index
      (ISI(0,120)), and Whole Body Insulin Sensitivity Index (WBISI) for whole body IR
      are the indices calculated after Oral Glucose Tolerance Test (OGTT). We used
      these indices as noninvasive methods of IR (inverse of insulin sensitivity)
      estimation and compared hepatic/peripheral components of whole body IR in NAFLD.
      Methods. 113 morbidly obese, nondiabetic subjects who underwent gastric bypass
      surgery and intraoperative liver biopsy were included in the study. OGTT was
      performed preoperatively and the indices were calculated. Subjects were divided
      into closely matched groups as normal, fatty liver (FL) and Non-Alcoholic
      Steatohepatitis (NASH) based on histology. Results. Whole body IR was
      significantly higher in both FL and NASH groups (NAFLD) as compared to Normal,
      while hepatic IR was higher only in NASH from Normal. Conclusions. FL is a
      manifestation of peripheral IR but not hepatic IR.

PMID- 20798876
TI  - The avian proghrelin system.
AB  - To understand how the proghrelin system functions in regulating growth hormone
      release and food intake as well as defining its pleiotropic roles in such diverse
      physiological processes as energy homeostasis, gastrointestinal tract function
      and reproduction require detailed knowledge of the structure and function of the
      components that comprise this system. These include the preproghrelin gene that
      encodes the proghrelin precursor protein from which two peptide hormones, ghrelin
      and obestatin, are derived and the cognate receptors that bind proghrelin-derived
      peptides to mediate their physiological actions in different tissues. Also key to
      the functioning of this system is the posttranslational processing of the
      proghrelin precursor protein and the individual peptides derived from it. While
      this system has been intensively studied in a variety of animal species and
      humans over the last decade, there has been considerably less investigation of
      the avian proghrelin system which exhibits some unique differences compared to
      mammals. This review summarizes what is currently known about the proghrelin
      system in birds and offers new insights into the nature and function of this
      important endocrine system. Such information facilitates cross-species
      comparisons and contributes to our understanding of the evolution of the
      proghrelin system.

PMID- 20798877
TI  - The relation of coffee consumption to serum uric Acid in Japanese men and women
      aged 49-76 years.
AB  - Objective. Few studies have suggested an inverse relation between coffee intake
      and serum concentrations of uric acid (UA), but none has addressed the relation
      in men and women separately. We examined the relation between coffee intake and
      serum UA levels in free-living middle-aged and elderly men and women in Fukuoka,
      Japan. Methods. Study subjects were derived from the baseline survey of a cohort
      study on lifestyle-related diseases, and included 11.662 men and women aged 49-76
      years; excluded were those with medication for gout and hyperuricemia, use of
      diuretic drugs, and medical care for cancer or chronic kidney disease.
      Statistical adjustment was made for body mass index, alcohol use, hypertension,
      diabetes mellitus, and other factors. Results. There were inverse associations of
      coffee consumption with serum UA concentrations and hyperuricemia in men
      regardless of adjustment for covariates. Women showed a statistically
      significant, but weaker, inverse association between coffee and serum UA levels
      after allowance for the confounding factors. Conclusion. The findings add to
      evidence for a protective association between coffee intake and hyperuricemia.

PMID- 20798878
TI  - The ethics of rationing of critical care services: should technology assessment
      play a role?
AB  - The costs of health care continue to increase rapidly and steeply in the United
      States. One area of great expense is that of intensive care units (ICUs). The
      causes of inflation have not been addressed effectively. ICU resources could
      become stretched such that they may no longer be available. This paper discusses
      some of the ethics and concerns behind decision making when providing ICU
      services in the United States. In particular, the use of electronic records with
      decision making tools, risk-analysis methods, and documentation of patient wishes
      for extraordinary care may help with better utilization of resources in the
      future.

PMID- 20798879
TI  - Structural properties of g,t-parallel duplexes.
AB  - The structure of G,T-parallel-stranded duplexes of DNA carrying similar amounts
      of adenine and guanine residues is studied by means of molecular dynamics (MD)
      simulations and UV- and CD spectroscopies. In addition the impact of the
      substitution of adenine by 8-aminoadenine and guanine by 8-aminoguanine is
      analyzed. The presence of 8-aminoadenine and 8-aminoguanine stabilizes the
      parallel duplex structure. Binding of these oligonucleotides to their target
      polypyrimidine sequences to form the corresponding G,T-parallel triplex was not
      observed. Instead, when unmodified parallel-stranded duplexes were mixed with
      their polypyrimidine target, an interstrand Watson-Crick duplex was formed. As
      predicted by theoretical calculations parallel-stranded duplexes carrying 8
      aminopurines did not bind to their target. The preference for the parallel-duplex
      over the Watson-Crick antiparallel duplex is attributed to the strong
      stabilization of the parallel duplex produced by the 8-aminopurines. Theoretical
      studies show that the isomorphism of the triads is crucial for the stability of
      the parallel triplex.

PMID- 20798880
TI  - Mitochondria, cognitive impairment, and Alzheimer's disease.
AB  - To date, the beta amyloid (Abeta) cascade hypothesis remains the main
      pathogenetic model of Alzheimer's disease (AD), but its role in the majority of
      sporadic AD cases is unclear. The "mitochondrial cascade hypothesis" could
      explain many of the biochemical, genetic, and pathological features of sporadic
      AD. Somatic mutations in mitochondrial DNA (mtDNA) could cause energy failure,
      increased oxidative stress, and accumulation of Abeta, which in a vicious cycle
      reinforce the mtDNA damage and the oxidative stress. Despite the evidence of
      mitochondrial dysfunction in AD, no causative mutations in the mtDNA have been
      detected so far. Indeed, results of studies on the role of mtDNA haplogroups in
      AD are controversial. In this review we discuss the role of the mitochondria, and
      especially of the mtDNA, in the cascade of events leading to neurodegeneration,
      dementia, and AD.

PMID- 20798881
TI  - Genetic Variability and Phylogenetic Relationships within Trypanosoma cruzi I
      Isolated in Colombia Based on Miniexon Gene Sequences.
AB  - Phylogenetic studies of Trypanosoma cruzi have identified the existence of two
      groups: T. cruzi I and T. cruzi II. There are aspects that still remain unknown
      about the genetic variability within the T. cruzi I group. Given its
      epidemiological importance, it is necessary to have a better understanding of T.
      cruzi transmission cycles. Our purpose was to corroborate the existence of
      haplotypes within the T. cruzi I group and to describe the genetic variability
      and phylogenetic relationships, based on single nucleotide polymorphisms (SNPs)
      found in the miniexon gene intergenic region, for the isolates from different
      hosts and epidemiological transmission cycles in Colombian regions. 31 T. cruzi
      isolates were molecularly characterized. Phylogenetic relationships within T.
      cruzi I isolates showed four haplotype groups (Ia-Id), associated with their
      transmission cycle. In previous studies, we reported that haplotype Ia is mainly
      associated with the domestic cycle and domiciliated Rhodnius prolixus. Haplotype
      Ib is associated with the domestic cycle and peridomestic cycle, haplotype Ic is
      closely related with the peridomestic cycle, and haplotype Id is strongly
      associated with the sylvatic cycle. The phylogenetic methodologies applied in
      this study are tools that bolster the associations among isolates and thus shed
      light on Chagas disease epidemiology.

PMID- 20798882
TI  - The Role of Adipokines in Understanding the Associations between Obesity and
      Depression.
AB  - Objective. Two major causes of disability, major depression and obesity, share
      overlapping psychosocial and pathophysiological etiologies. Studies are now
      focused on biological mechanisms linking the two illnesses, and there is interest
      in the role that adipokines may have in mediating the association between obesity
      and depression. We reviewed the literature to look at what is currently known
      about this association, focusing on the adipokines leptin, adiponectin, and
      resistin. Methods. A MEDLINE search, citing articles from 1966 onward,
      supplemented by a review of bibliographies, was conducted to identify relevant
      studies. Results. This paper identified plausible pathways underlying a link
      between adipokines and depression. Only a few studies have yet been conducted
      specifically examining these biomarkers in patients with depression, but the
      results are intriguing. Conclusion. This paper is one of the first to examine the
      association between adipokines and depression. It provides an overview of the
      physiological role of adipokines and summarizes the data suggesting that they may
      be dysregulated in major depression. This area of research may become
      increasingly important as new treatment strategies are developed.

PMID- 20798883
TI  - Influence of XRCC1 Genetic Polymorphisms on Ionizing Radiation-Induced DNA Damage
      and Repair.
AB  - It is well known that ionizing radiation (IR) can damage DNA through a direct
      action, producing single- and double-strand breaks on DNA double helix, as well
      as an indirect effect by generating oxygen reactive species in the cells. Mammals
      have evolved several and distinct DNA repair pathways in order to maintain
      genomic stability and avoid tumour cell transformation. This review reports
      important data showing a huge interindividual variability on sensitivity to IR
      and in susceptibility to developing cancer; this variability is principally
      represented by genetic polymorphisms, that is, DNA repair gene polymorphisms. In
      particular we have focussed on single nucleotide polymorphisms (SNPs) of XRCC1, a
      gene that encodes for a scaffold protein involved basically in Base Excision
      Repair (BER). In this paper we have reported and presented recent studies that
      show an influence of XRCC1 variants on DNA repair capacity and susceptibility to
      breast cancer.

PMID- 20798885
TI  - Neuroprotective Effects of Centella asiatica against Intracerebroventricular
      Colchicine-Induced Cognitive Impairment and Oxidative Stress.
AB  - Oxidative stress appears to be an early event involved in the pathogenesis of
      Alzheimer's disease. The present study was designed to investigate the
      neuroprotective effects of Centella asiatica against colchicine-induced memory
      impairment and oxidative damage in rats. Colchicine (15 mug/5 muL) was
      administered intracerebroventricularly in the lateral ventricle of male wistar
      rats. Morris water maze and plus-maze performance tests were used to assess
      memory performance tasks. Various biochemical parameters such as lipid
      peroxidation, nitrite, reduced glutathione, glutathione-S-transferase, superoxide
      dismutase, acetylcholinesterase were also assessed. ICV colchicine resulted
      marked memory impairment and oxidative damage. Chronic treatment with Centella
      asiatica extract (150 and 300 mg/kg, p.o.) for a period of 25 days, beginning 4
      days prior to colchicine administration, significantly attenuated colchicine
      induced memory impairment and oxidative damage. Besides, Centella asiatica
      significantly reversed colchicines administered increase in acetylcholinesterase
      activity. Thus, present study indicates protective effect of Centella asiatica
      against colchicine-induced cognitive impairment and associated oxidative damage.

PMID- 20798884
TI  - Interactions of gastrointestinal peptides: ghrelin and its anorexigenic
      antagonists.
AB  - Food intake behaviour and energy homeostasis are strongly regulated by a complex
      system of humoral factors and nerval structures constituting the brain-gut-axis.
      To date the only known peripherally produced and centrally acting peptide that
      stimulates food intake is ghrelin, which is mainly synthesized in the stomach.
      Recent data indicate that the orexigenic effect of ghrelin might be influenced by
      other gastrointestinal peptides such as cholecystokinin (CCK), bombesin, desacyl
      ghrelin, peptide YY (PYY), as well as glucagon-like peptide (GLP). Therefore, we
      will review on the interactions of ghrelin with several gastrointestinal factors
      known to be involved in appetite regulation in order to elucidate the
      interdependency of peripheral orexigenic and anorexigenic peptides in the control
      of appetite.

PMID- 20798886
TI  - Staging of Alzheimer's pathology in triple transgenic mice: a light and electron
      microscopic analysis.
AB  - The age-related pathological cascade underlying intraneuronal tau formation in
      3xTg-AD mice, which harbor the human APP(Swe), PS1(M126V) , and Tau(P301L) gene
      mutations, remains unclear. At 3 weeks of age, AT180, Alz50, MC1, AT8, and PHF-1
      intraneuronal immunoreactivity appeared in the amygdala and hippocampus and at
      later ages in the cortex of 3xTg-AD mice. AT8 and PHF-1 staining was fixation
      dependent in young mutant mice. 6E10 staining was seen at all ages. Fluorescent
      immunomicroscopy revealed CA1 neurons dual stained for 6E10 and Alz50 and single
      Alz50 immunoreactive neurons in the subiculum at 3 weeks and continuing to 20
      months. Although electron microscopy confirmed intraneuronal cytoplasmic Alz50,
      AT8, and 6E10 reaction product in younger 3xTg-AD mice, straight filaments
      appeared at 23 months of age in female mice. The present data suggest that other
      age-related biochemical mechanisms in addition to early intraneuronal
      accumulation of 6E10 and tau underlie the formation of tau filaments in 3xTg-AD
      mice.

PMID- 20798887
TI  - Evaluation of Hexane Extract of Tuber of Root of Cyperus rotundus Linn
      (Cyperaceae) for Repellency against Mosquito Vectors.
AB  - Hexane extract of tuber of plant Cyperus rotundus (Cyperaceae) was screened under
      laboratory conditions for repellent activity against mosquito vector Anopheles
      culicifacies Giles species A (Diptera: Culicidae), Anopheles stephensi Liston
      (Diptera: Culicidae), and Culex quinquefasciatus Say (Diptera: Culicidae). The
      Cyperus rotundus tuber extract was used to determine their effect on mosquito
      vector, and comparison with the DEET (NN Diethyl 1-3 methyl Benzamide, formerly
      known as diethyl 1-m-toluamide). The tuber extracts showed more effective at all
      the dose. Result obtained from the laboratory experiment showed that the tuber
      extracts are more effective for repellency of allthe mosquito vector even at low
      dose. Clear dose response relationships were established with the highest dose of
      10% tuber extract evoking 100% repellency. Percent protection obtained against
      An. culicifacies Giles species A 100% repellency in 4 hours, 6 hours, An.
      stephensi 100% repellency in 6 hours and Cx. quinquefasciatus was 100% repellency
      in 6 hours at the 10% concentration. Against DEET- 2.5% An. culicifacies A 100%
      repellency in 1 hour, 2 hours, 6 hours, An. stephensi have shown 100% repellency
      in 6 hours, and Culex quinquefasciatus have shown 100% repellency in 1 hour, 2
      hours, 6 hours. The consolidated data of the repellency observed in different
      species is given and it is evident that the over all repellency rates varied
      between 80 and 100% for different repellents concentrations (2.5%, 5%, and 10%).
      The extract can be applied as an effective personal protective measure against
      mosquito bites.

PMID- 20798888
TI  - Sagittal abdominal diameter as a screening tool in clinical research: cutoffs for
      cardiometabolic risk.
AB  - Background. Waist girth and BMI are commonly used as markers of cardiometabolic
      risk. Accumulating data however suggest that sagittal abdominal diameter (SAD) or
      "abdominal height" may be a better marker of intra-abdominal adiposity and
      cardiometabolic risk. We aimed to identify cutoffs for SAD using a
      cardiometabolic risk score. Design. A population-based cross-sectional study.
      Methods. In 4032 subjects (1936 men and 2096 women) at age 60, different
      anthropometric variables (SAD, BMI, waist girth, and waist-to-hip ratio) were
      measured and cardiometabolic risk score calculated. ROC curves were used to
      assess cutoffs. Results. Among men SAD showed the strongest correlations to the
      majority of the individual risk factors; whereas in women SAD was equal to that
      of waist girth. In the whole sample, the area under the ROC curve was highest for
      SAD. The optimal SAD cutoff for an elevated cardiometabolic risk score in men was
      approximately 22 cm (95%CI; 21.6 to 22.8) and in women approximately 20 cm
      (95%CI; 19.4 to 20.8). These cutoffs were similar if the Framingham risk score
      was used. Conclusions. These cutoffs may be used in research and screening to
      identify "metabolically obese" men who would benefit from lifestyle and
      pharmacological interventions. These results need to be verified in younger age
      groups.

PMID- 20798889
TI  - Effects of immunomodulatory substances on phagocytosis of abeta(1-42) by human
      microglia.
AB  - Glial activation and increased inflammation characterize neuropathology in
      Alzheimer's disease (AD). The aim was to develop a model for studying
      phagocytosis of beta-amyloid (Abeta) peptide by human microglia and to test
      effects thereupon by immunomodulatory substances. Human CHME3 microglia showed
      intracellular Abeta(1-42) colocalized with lysosome-associated membrane protein
      2, indicating phagocytosis. This was increased by interferon-gamma, and to a
      lesser degree with Protollin, a proteosome-based adjuvant. Secretion of brain
      derived neurotrophic factor (BDNF) was decreased by Abeta(1-42) and by interferon
      gamma and interleukin-1beta. These cytokines, but not Abeta(1-42), stimulated
      interleukin-6 release. Microglia which phagocytosed Abeta(1-42) exhibited a
      higher degree of expression of interleukin-1 receptor type I and inducible nitric
      oxide synthase. In conclusion, we show that human microglia are able to
      phagocytose Abeta(1-42) and that this is associated with expression of
      inflammatory markers. Abeta(1-42) and interferon-gamma decreased BDNF secretion
      suggesting a new neuropathological role for Abeta(1-42) and the inflammation
      accompanying AD.

PMID- 20798890
TI  - Exploration of the interrupted Fischer indolization reaction.
AB  - A convergent method to access the fused indoline ring system present in a
      multitude of bioactive molecules has been developed. The strategy involves the
      condensation of hydrazines with latent aldehydes to ultimately deliver indoline
      containing products by way of an interrupted Fischer indolization sequence. The
      method is convergent, mild, operationally simple, broad in scope, and can be used
      to access enantioenriched products. In addition, our approach is amenable to the
      synthesis of furoindoline and pyrrolidinoindoline natural products as
      demonstrated by the concise formal total syntheses of physovenine and
      debromoflustramine B. The strategy will likely enable the synthesis of more
      complex targets such as the communesin alkaloids.

PMID- 20798891
TI  - Dimerization of functional pyrroloindolizines for the synthesis of complex
      myrmicarin alkaloids.
AB  - The union of functionalized pyrroloindolizines for the synthesis of heterodimeric
      products relevant to myrmicarin alkaloids is described. Design and synthesis of
      tricyclic substrates and new methods for their union enable the investigation of
      late-stage cyclopentannulation strategies. The rapid assembly of dimeric
      structures using unique modes of pyrroloindolizine reactivity presents a concise
      approach to the dimeric myrmicarins and relevant derivatives.

PMID- 20798892
TI  - Stimulation of DNA Glycosylase Activities by XPC Protein Complex: Roles of
      Protein-Protein Interactions.
AB  - We showed that XPC complex, which is a DNA damage detector for nucleotide
      excision repair, stimulates activity of thymine DNA glycosylase (TDG) that
      initiates base excision repair. XPC appeared to facilitate the enzymatic turnover
      of TDG by promoting displacement from its own product abasic site, although the
      precise mechanism underlying this stimulation has not been clarified. Here we
      show that XPC has only marginal effects on the activity of E. coli TDG homolog
      (EcMUG), which remains bound to the abasic site like human TDG but does not
      significantly interacts with XPC. On the contrary, XPC significantly stimulates
      the activities of sumoylated TDG and SMUG1, both of which exhibit quite different
      enzymatic kinetics from unmodified TDG but interact with XPC. These results point
      to importance of physical interactions for stimulation of DNA glycosylases by XPC
      and have implications in the molecular mechanisms underlying mutagenesis and
      carcinogenesis in XP-C patients.

PMID- 20798893
TI  - The roles of motilin and ghrelin in gastrointestinal motility.
AB  - In structure, ghrelin resembles motilin. The two peptides are considered to be
      members of the motilin-ghrelin peptide family. Motilin is considered to be an
      endocrine regulator of the interdigestive migrating contractions, the fasted
      motor pattern in the gastrointestinal (GI) tract. It has been reported that
      ghrelin stimulates GI motility. The gastrokinetic capacity of ghrelin has been
      well documented in the rodent. However, there have been few positive reports of
      the gastrokinetic capacity of ghrelin in dogs. Some reports with human subjects
      have shown that an i.v. ghrelin injection accelerated gastric emptying of a meal
      and improved meal-related symptoms. These results suggest that ghrelin has
      potential as a prokinetic. However, it seems unlikely that plasma ghrelin would
      play a physiological role in these digestive physiological events and stimulate
      gastric emptying, as these outcomes would appear to be in contradiction with the
      suppression of the endogenous release of ghrelin after eating. The physiological
      roles of ghrelin need to be clarified.

PMID- 20798894
TI  - In stent restenosis predictors after carotid artery stenting.
AB  - Purpose. The long-term efficacy of carotid artery stenting is debated. Predictors
      of stent restenosis are not fully investigated. Our aim was to assess the
      incidence of long term restenosis after CAS and to identify some predictors of
      restenosis. Methods. We retrospectively selected 189 treated patients and we
      obtained the survival Kaplan-Meier curves for overall survival, for freedom from
      stroke or death and from restenosis. To correlate clinical, radiological, and
      procedural variables to stent restenosis, an univariate analysis was performed
      while to determine independent predictors of restenosis, a multivariate analysis
      was applied. Results. At 1, 3, and 5 years, the cumulative overall survival rate
      was 98%, 94%, and 92% with a cumulative primary patency rate of 87%, 82.5%, and
      82.5%. The percentage residual stenosis after CAS and multiple stents deployment
      were independent predictors of restenosis, while diabetes and tumors are
      suggestive but not significant predictors of restenosis. Conclusions. In our CAS
      experience, encouraging long-term results seem to derive from both neurological
      event free rate and restenosis incidence. Adequate recanalization of the treated
      vessel is important to limit the development of stent restenosis. Multiple stents
      deployment, and with less evidence, diabetes, or neoplasms has to be considered
      to facilitate restenosis.

PMID- 20798895
TI  - A general enantioselective route to the chamigrene natural product family.
AB  - Described in this report is an enantioselective route toward the chamigrene
      natural product family. The key disconnections in our synthetic approach include
      sequential enantioselective decarboxylative allylation and ring-closing olefin
      metathesis to form the all-carbon quaternary stereocenter and spirocyclic core
      present in all members of this class of compounds. The generality of this
      strategy is demonstrated by the first total syntheses of elatol and the proposed
      structure of laurencenone B, as well as the first enantioselective total
      syntheses of laurencenone C and alpha-chamigrene. A brief exploration of the
      substrate scope of the enantioselective decarboxylative allylation/ring-closing
      metathesis sequence with fully substituted vinyl chlorides is also presented.

PMID- 20798896
TI  - Inhibition binding studies of glycodendrimer-lectin interactions using surface
      plasmon resonance.
AB  - Understanding protein-carbohydrate interactions is essential for elucidating
      biological pathways and cellular mechanisms but is often difficult due to the
      prevalence of multivalent interactions. Here, we evaluate the multivalent
      glycodendrimer framework as a means to describe the inhibition potency of
      multivalent mannose-functionalized dendrimers using surface plasmon resonance
      (SPR). Using highly robust, mannose-functionalized dithiol self-assembled
      monolayers on gold surfaces, we found that glycodendrimers were efficient
      inhibitors of protein-carbohydrate interactions. IC(50) values ranging from 260
      nM to 13 nM were obtained for mannose-functionalized dendrimers with Concanavalin
      A.

PMID- 20798897
TI  - Synthesis and chemical diversity analysis of bicyclo[3.3.1]non-3-en-2-ones.
AB  - Functionalized bicyclo[3.3.1]non-3-en-2-ones are obtained from commercially
      available phenols by a hypervalent iodine oxidation, enone epoxidation, epoxide
      thiolysis, and intramolecular aldol reaction sequence. Reaction optimization
      studies identified room temperature as well as microwave-mediated procedures,
      providing moderate to good yields (57%-88%) in the thiophenol-mediated epoxide
      opening and intramolecular aldol reaction. In addition, the isolation of a key
      intermediate and in situ NMR studies supported the mechanistic hypothesis. The
      bicyclic ring products occupy novel chemical space according to ChemGPS and
      Chemaxon chemical diversity and cheminformatics analyses.

PMID- 20798898
TI  - A program for ligation at threonine sites: application to the controlled total
      synthesis of glycopeptides.
AB  - A method by which to accomplish formal threonine ligation has been developed. The
      method accomplishes ligations of two peptide domains. We have also demonstrated
      the ability to successfully ligate two independent glycopeptide domains.

PMID- 20798899
TI  - Examining the pathways linking chronic sleep restriction to obesity.
AB  - A growing number of studies have identified chronic sleep restriction as a
      potential risk factor for obesity. This could have important implications for how
      obesity is prevented and managed, but current understanding of the processes
      linking chronic sleep restriction to obesity is incomplete. In this paper, we
      examined some of the pathways that could underlie the relationship between
      chronic sleep restriction and obesity. This involved exploring some of the
      potential environmental, health, behavioral, and sociodemographic determinants of
      chronic sleep restriction, which require further investigation in this context.
      Three pathways that could potentially link chronic sleep restriction to obesity
      were then examined: (1) altered neuroendocrine and metabolic function, (2)
      impaired glucose regulation, and (3) waking behavior. The selected pathways
      linking chronic sleep restriction to obesity reviewed in this paper are presented
      in a schematic representation; this may be used to guide future research in this
      area. This area of research is important because it may lead to more effective
      interventions and strategies to combat the present obesity epidemic.

PMID- 20798902
TI  - Ortho-directed functionalization of arenes using magnesate bases.
AB  - Ortho-directed functionalisation of arenes using lithium alkylmagnesate bases
      were achieved, demonstrating the potential use of arylmagnesates as suitable
      arylanions, without a further transmetallation step, for challenging
      functionalizations such as fluorination, hydroxylation, arylation, vinylation and
      alkylation through epoxide ring-opening.

PMID- 20798901
TI  - Metabolic and cardiovascular effects of ghrelin.
AB  - Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is
      synthesized as a preprohormone and then proteolytically processed to yield a 28
      amino acid peptide. This peptide was originally reported to induce growth hormone
      release; large evidence, however, has indicated many other physiological
      activities of ghrelin, including regulation of food intake and energy balance, as
      well as of lipid and glucose metabolism. Ghrelin receptors have been detected in
      the hypothalamus and the pituitary, but also in the cardiovascular system, where
      ghrelin exerts beneficial hemodynamic activities. Ghrelin administration acutely
      improves endothelial dysfunction by increasing nitric oxide bioavailability and
      normalizes the altered balance between endothelin-1 and nitric oxide within the
      vasculature of patients with metabolic syndrome. Other cardiovascular effects of
      ghrelin include improvement of left ventricular contractility and cardiac output,
      as well as reduction of arterial pressure and systemic vascular resistance. In
      addition, antinflammatory and antiapoptotic actions of ghrelin have been reported
      both in vivo and in vitro. This review summarizes the most recent findings on the
      metabolic and cardiovascular effects of ghrelin through GH-dependent and 
      independent mechanisms and the possible role of ghrelin as a therapeutic molecule
      for treating cardiovascular diseases.

PMID- 20798903
TI  - KZn(4)SbO(7) and KZn(4)Sb(3)O(12): syntheses, structures and photophysics of
      Sb(5+) control materials.
AB  - Two novel compounds KZn(4)SbO(7) (1) and KZn(4)Sb(3)O(12) (2) having quasi-white
      light emission and second-harmonic generation are prepared, and their single
      crystal structures are characterized as P6(3)mc and R3 space groups,
      respectively. The crystal structure transition from high symmetry P6(3)mc of 1 to
      low symmetry R3 of 2 arises from the large contents of Sb(5+) diluter in wurtzite
      type ZnO crystals (ionic ratio of Sb(5+)/Zn(2+) = 1/4 and 3/4 for crystals 1 and
      2). The lifetime and quantum efficiency of luminescence are measured, and the
      density of states and frequency doubling coefficients are calculated for the two
      compounds. The strong charge transfers from O(2-) to Sb(5+), and blue-shifts of
      absorption edge and emission bands originate from a large Sb(5+) ion content for
      compound 2. Further, large charge transfer from O(2-) to Sb(5+) lead to high
      quantum efficiency and low lifetime, and weak second-harmonic generation
      intensity for compound 2.

PMID- 20798904
TI  - Selective and sensitive detection and quantification of arylamine N
      acetyltransferase 2 by a ratiometric fluorescence probe.
AB  - A novel NAT2 specific probe has been developed for sensitive detection of the
      activity of NAT2. Upon NAT2 catalyzed acetylation of the molecule to N-acetyl
      amonafide, the ratiometric response of fluorescence with significant changes in
      wavelength and intensity is observed. Its significant application potential has
      been successfully demonstrated in cellular systems.

PMID- 20798900
TI  - Modeling presenilin-dependent familial Alzheimer's disease: emphasis on
      presenilin substrate-mediated signaling and synaptic function.
AB  - Mutations in PSEN genes, which encode presenilin proteins, cause familial early
      onset Alzheimer's disease (AD). Transgenic mouse models based on coexpression of
      familial AD-associated presenilin and amyloid precursor protein variants
      successfully mimic characteristic pathological features of AD, including plaque
      formation, synaptic dysfunction, and loss of memory. Presenilins function as the
      catalytic subunit of gamma-secretase, the enzyme that catalyzes intramembraneous
      proteolysis of amyloid precursor protein to release beta-amyloid peptides.
      Familial AD-associated mutations in presenilins alter the site of gamma-secretase
      cleavage in a manner that increases the generation of longer and highly
      fibrillogenic beta-amyloid peptides. In addition to amyloid precursor protein,
      gamma-secretase catalyzes intramembrane proteolysis of many other substrates
      known to be important for synaptic function. This paper focuses on how various
      animal models have enabled us to elucidate the physiological importance of
      diverse gamma-secretase substrates, including amyloid precursor protein and
      discusses their roles in the context of cellular signaling and synaptic function.

PMID- 20798909
TI  - Return to work and occupational physicians' management of common mental health
      problems--process evaluation of a randomized controlled trial.
AB  - OBJECTIVE: The aim of this study was to examine the adherence of occupational
      physicians (OP) to the Dutch guideline on the management of common mental health
      problems and its effect on return to work as part of the process evaluation of a
      trial comparing adherence to the guideline to care as usual. The first hypothesis
      was that guideline adherence among the "guideline group" will be higher compared
      to the "usual care group". The second hypothesis was that better guideline
      adherence by the occupational physician will be associated with earlier return to
      work. METHODS: In a randomized controlled trial, five participating OP had to
      provide care based on the Dutch guideline to 240 police workers with common
      mental health problems (the "guideline group"). The same OP had to provide usual
      care to the participants in the control group (the "usual care" group), including
      minimal involvement and easy access to a psychologist. In evaluating the process,
      we assessed guideline adherence via an audit of medical files, using 20 guideline
      based performance indicators. Mean rates of guideline adherence were related to
      the duration until first and full return to work, using a Cox proportional
      hazards model. RESULTS: The mean rate of the sum score of guideline adherence was
      10 in a range of 0-20 [standard deviation (SD) 1.8] and did not significantly
      differ between the intervention and control group. Mean better guideline
      adherence showed a statistically significant association with a shorter time to
      first and full return to work [hazard ratio 1.1; 95% confidence interval (95% CI)
      1.0-1.2], which was explained by keeping more regular contact with the worker and
      the work system and better monitoring of stagnation or return to work.
      CONCLUSIONS: No contrast in guideline adherence was found between guideline-based
      versus usual care. This can be explained by contamination between the guideline
      and usual care group. Even though guideline adherence was only average, better
      adherence predicted earlier return to work. Guidelines for management of common
      mental health problems and return to work should focus on regular contact with
      the worker and the work organisation.

PMID- 20798910
TI  - Editorial-Neurowoche 2010: a highlight of neuromedicine in Germany.

PMID- 20798911
TI  - Isolated PICA dissection: an unusual complication of scuba diving : case report
      and review of the literature.

PMID- 20798912
TI  - Celastrol suppresses invasion of colon and pancreatic cancer cells through the
      downregulation of expression of CXCR4 chemokine receptor.
AB  - Although metastasis accounts for >90% of cancer-related deaths, no therapeutic
      that targets this process has yet been approved. Because the chemokine receptor
      CXCR4 is one of the targets closely linked with tumor metastasis, inhibitors of
      this receptor have the potential to abrogate metastasis. In the current report,
      we demonstrate that celastrol can downregulate the CXCR4 expression on breast
      cancer MCF-7 cells stably transfected with HER2, an oncogene known to induce the
      chemokine receptor. Downregulation of CXCR4 by the triterpenoid was not cell type
      specific as downregulation occurred in colon cancer, squamous cell carcinoma, and
      pancreatic cancer cells. Decrease in CXCR4 expression was not due to proteolysis
      as neither proteasome inhibitors nor lysosomal stabilization had any effect.
      Quantitative reverse transcription polymerase chain reaction analysis revealed
      that downregulation of CXCR4 messenger RNA (mRNA) by celastrol occurred at the
      translational level. Chromatin immunoprecipitation analysis revealed regulation
      at the transcriptional level as well. Abrogation of the chemokine receptor by
      celastrol or by gene-silencing was accompanied by suppression of invasiveness of
      colon cancer cells induced by CXCL12, the ligand for CXCR4. This effect was not
      cell type-specific as celastrol also abolished invasiveness of pancreatic tumor
      cells, and this effect again correlated with the disappearance of both the CXCR4
      mRNA and CXCR4 protein. Other triterpenes, such as withaferin A and gedunin,
      which are known to inhibit Hsp90, did not downregulate CXCR4 expression,
      indicating that the effects were specific to celastrol. Overall, these results
      show that celastrol has potential in suppressing invasion and metastasis of
      cancer cells by down-modulation of CXCR4 expression.

PMID- 20798914
TI  - [When guidelines are confronted with health care reality: purpose of guidelines
      from the perspective of a psychiatrist].
AB  - The National Health Care guidelines on unipolar depression play a leading role
      regarding the multitude of players providing general care services, regarding
      scientific research and, last but not least, regarding common etiologic and
      therapeutic concepts as perceived by affected people and their relatives. In
      terms of health care, depression as a universal disorder comprises qualitative
      and quantitative aspects. For practicing neurologists/psychiatrists the
      guidelines provides many suggestions for different forms of treatment of the many
      kinds of depressive patients. When using a comprehensive approach, the criteria
      of evidence-based medicine are particularly important for practicing
      psychiatrists regarding the knowledge based on medical experience and patients
      preferences. It is important to point out that the hitherto fervently debated
      treatment dichotomy of psychotherapy versus pharmacotherapy is beginning to
      diminish. This is also reflected by the holistic perception of diseases and
      treatment approaches prevailing among established psychiatrists and the apparent
      development of health care quality towards individualized medicine.

PMID- 20798913
TI  - The chemokine receptor CXCR5 is pivotal for ectopic mucosa-associated lymphoid
      tissue neogenesis in chronic Helicobacter pylori-induced inflammation.
AB  - Ectopic lymphoid follicles are a key feature of chronic inflammatory autoimmune
      and infectious diseases, such as rheumatoid arthritis, Sjogren's syndrome, and
      Helicobacter pylori-induced gastritis. Homeostatic chemokines are considered to
      be involved in the formation of such tertiary lymphoid tissue. High expression of
      CXCL13 and its receptor, CXCR5, has been associated with the formation of ectopic
      lymphoid follicles in chronic infectious diseases. Here, we defined the role of
      CXCR5 in the development of mucosal tertiary lymphoid tissue and gastric
      inflammation in a mouse model of chronic H. pylori infection. CXCR5-deficient
      mice failed to develop organized gastric lymphoid follicles despite similar
      bacterial colonization density as infected wild-type mice. CXCR5 deficiency
      altered Th17 responses but not Th1-type cellular immune responses to H. pylori
      infection. Furthermore, CXCR5-deficient mice exhibited lower H. pylori-specific
      serum IgG and IgA levels and an overall decrease in chronic gastric immune
      responses. In conclusion, the development of mucosal tertiary ectopic follicles
      during chronic H. pylori infection is strongly dependent on the CXCL13/CXCR5
      signaling axis, and lack of de novo lymphoid tissue formation attenuates chronic
      immune responses.

PMID- 20798915
TI  - [The concept of the development of S3 guidelines: additional benefit compared to
      traditional standards, problems and solutions].
AB  - Guidelines for the diagnosis and treatment of psychiatric disorders developed on
      the highest qualitative methodical standard cover reliable decision guidance and
      are an important instrument of quality improvement in health care. They have to
      be accessible with little effort and should be concise and clearly presented to
      be used in daily routine. Early integration of members of the different
      professions, patients and their care givers into the development process is
      essential for acceptance. The development process of a S3 guideline is complex
      and poses a difficult challenge to personal manpower and funding, which is met by
      the associations of the Association of Medical Societies in Germany. Further
      scientific discussion is necessary to find adequate solutions for problematic
      topics or potential distortion, such as the consequences of inadequate reporting
      of studies, insufficient recording and reporting of the risk of damage,
      unpublished data and lacking interest of sponsors in specific topics.

PMID- 20798916
TI  - [Guideline intentions of the German Society of Psychiatry, Psychotherapy and
      Nervous Diseases (DGPPN)].
AB  - The practice guidelines of the German Society of Psychiatry, Psychotherapy and
      Nervous Diseases (DGPPN) include systematically developed and evidence-based
      treatment recommendations which assist clinicians and patients in making
      decisions about appropriate treatment for specific conditions. The intentions of
      practice guidelines are to improve the quality of care and the outcome of mental
      diseases. This paper describes the methodology behind the development of the
      guidelines and lists the already existing practice guidelines as well as the
      guidelines actually being developed. In addition, it is outlined how quality
      indicators may be derived from guidelines. A major aim of the German Society of
      Psychiatry, Psychotherapy and Nervous Diseases (DGPPN) is to assure the quality
      of inpatient and outpatient care of the mentally ill by developing evidence-based
      consensus guidelines.

PMID- 20798917
TI  - [Functional imaging of deep brain stimulation in idiopathic Parkinson's disease].
AB  - Functional brain imaging allows the effects of deep brain stimulation (DBS) on
      the living human brain to be investigated. In patients with advanced Parkinson's
      disease (PD), positron emission tomography (PET) studies were undertaken at rest
      as well as under motor, cognitive or behavioral activation. DBS leads to a
      reduction of abnormal PD-related network activity in the motor system, which
      partly correlates with the improvement of motor symptoms. The local increase of
      energy consumption within the direct target area suggests a predominant
      excitatory influence of the stimulation current on neuronal tissue. Remote
      effects of DBS of the subthalamic nucleus (STN) on frontal association cortices
      indicate an interference of stimulation energy with associative and limbic basal
      ganglia loops. Taken together, functional brain imaging provides very valuable
      data for advancement of the DBS technique in PD therapy.

PMID- 20798919
TI  - Short-term outcomes with the AjustTM system: a new single incision sling for the
      treatment of stress urinary incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: To evaluate the efficacy and safety of the minimally
      invasive AjustTM system in the treatment of stress urinary incontinence. METHODS:
      This was a prospective multicentre study. All patients with primary urodynamic
      stress urinary incontinence were prospectively selected to receive the AjustTM
      procedure. The International Consultation on Incontinence-Short Form (ICI-SF),
      Women Irritative Prostate Symptoms Score (W-IPSS), PGI-S, and PGI-I
      questionnaires were used to evaluate the impact of incontinence and voiding
      dysfunction on QoL and to measure patient's perception of incontinence severity
      and improvement. RESULTS: From January 2009 to October 2009, 111 consecutive
      subjects were enrolled in the study. At 6 months, 102 were available for outcomes
      analysis. The subjective and objective cure rates were 85.7% and 91.4%,
      respectively. The ICI-SF and W-IPSS questionnaires showed a statistical
      significant improvement in symptom scores. CONCLUSIONS: In the short-term follow
      up, the AjustTM system was effective in restoring continence in more than 85% of
      subjects with a highly significant improvement in QoL.

PMID- 20798918
TI  - [Innovative MRI techniques in Parkinson's disease].
AB  - Brain imaging enables the investigation of brain morphology and function in
      patients with Parkinson's disease (PD). Innovative magnetic resonance imaging
      (MRI) techniques have recently been established as a new research tool in PD.
      They are based on the investigation of neuronal tissue properties (MR
      relaxometry, SWI, DWI, DTI, VBM) and of cerebral perfusion and neuronal activity
      (ASL, fcMRI). Besides a better understanding of the pathophysiology of PD, these
      innovative MR techniques might be suitable for measuring progression of PD and
      the effect of therapeutic interventions on brain functioning. In the clinical
      setting, they could help to advance the differential diagnosis of parkinsonian
      disorders.

PMID- 20798920
TI  - Pubococcygeal activity on perineal ultrasound in incontinent women.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to investigate the
      applicability and reproducibility of perineal ultrasound (US) in the evaluation
      of the pubococcygeal muscle (PCM) activity in urinary incontinent women. METHODS:
      Thirty women were assessed twice by two examiners who measured the angle between
      the lateral bundles of the PCM. The 2D US on coronal view evaluated the PCM
      performance during squeezing, straining, and resting. RESULTS: There was
      significant correlation (p <= 0.001) in all measurements to both examiners,
      except for the contraction on their second assessment. The images showed
      asymmetries of muscle volume and activity. Five women (16.7%) had difficulty to
      rest after squeezing or straining, six (20%) first opened the muscle bundles when
      asked to squeeze them, and eight (26.7%) had no movement during different
      moments. CONCLUSIONS: The 2D perineal US on coronal view is useful to evaluate
      PCM activity. It is easily applicable and reproducible.

PMID- 20798921
TI  - Impact of overactive bladder and lower urinary tract symptoms on sexual health in
      Japanese women.
AB  - INTRODUCTION AND HYPOTHESIS: This study aims to assess whether lower urinary
      tract symptoms (LUTS) affect sexual function in Japanese females. METHODS: A
      multi-component questionnaire was mailed to 576 female hospital workers. It
      contained the Female Sexual Function Index (FSFI) and a self-administered
      questionnaire pertaining to LUTS. RESULTS: Of the 276 responses (overall response
      rate, 47.9%), 146 questionnaires were evaluable. LUTS had been experienced by 72
      (49.3%) of the respondents, 17 (11.6%) had urge urinary incontinence, and 35
      (24.0%) had stress urinary incontinence (SUI). The mean overall FSFI score was
      22.4 +/- 9.0. The mean FSFI score was not significantly different between women
      with LUTS and women without LUTS (23.2 +/- 9.3 and 21.6 +/- 8.8, respectively; P
      = 0.057). However, the mean FSFI score of women with SUI was significantly lower
      than that of women without it (P = 0.04). No other symptoms showed significant
      differences in FSFI scores. CONCLUSIONS: Our results suggest that sexual
      dysfunction is related to SUI.

PMID- 20798922
TI  - Randomized trial of fascia lata and polypropylene mesh for abdominal
      sacrocolpopexy: 5-year follow-up.
AB  - INTRODUCTION AND HYPOTHESIS: The purpose of this study is to evaluate the 5-year
      surgical outcomes of abdominal sacrocolpopexy among subjects randomized to
      receive polypropylene mesh or cadaveric fascia lata. METHODS: All 100 subjects
      from the original randomized clinical trial were eligible. Primary outcome was
      objective anatomic failure: any pelvic organ prolapse quantification (POP-Q)
      point >= - 1. Secondary outcome was clinical failure-presence of bulge or
      prolapse symptoms and either a POP-Q point C >= 1/2 TVL or any POP-Q point >0-and
      interim surgical re-treatment. Wilcoxon tests and Fisher's exact test were
      performed. RESULTS: Fifty-eight subjects returned for 5-year follow-up-29 mesh
      and 29 fascia. Objective anatomic success rates were: mesh, 93% (27/29) and
      fascia, 62% (18/29) (p = 0.02). Clinical success rates were: mesh, 97% (28/29)
      and fascia, 90% (26/29) (p = 0.61). CONCLUSIONS: Polypropylene mesh was superior
      to cadaveric fascia lata using objective anatomic outcomes. Success rates of mesh
      and fascia were comparable using a clinical definition that combined symptoms
      with anatomic measures.

PMID- 20798923
TI  - A fetal scalp electrode as a simple aid in the search for a lost needle fragment
      during sacrospinous ligament fixation.
AB  - A needle fragment was lost during a sacrospinous ligament fixation. This was
      recognized during the procedure, but could not be found at that moment. The
      patient complained of severe buttock pain postoperatively. The needle fragment
      was localized on CT scan of the pelvis. A fetal scalp electrode helped as a
      search device to localize the needle on X-ray during the secondary surgery. The
      patient was operated successfully and was free of pain after 6 weeks.

PMID- 20798924
TI  - A questionnaire on pelvic floor dysfunction postpartum.
AB  - INTRODUCTION AND HYPOTHESIS: the incidence of obstetric anal sphincter injuries
      is used in Sweden as a measurement of quality of care and this might influence
      the reporting. However, the correlation between reported diagnosis of pelvic
      floor injury at delivery and pelvic floor symptoms a year later is unknown. A
      questionnaire could identify such symptoms and provide beneficial feedback to
      obstetrical practices. METHODS: we made a cross-sectional study by sending out a
      questionnaire about pelvic floor dysfunction to 599 women depending on reported
      injury at delivery. The answers provided by the groups were then compared.
      RESULTS: the questionnaire identified women with pelvic floor dysfunction. Anal
      incontinence was most common among women with obstetric anal sphincter injuries
      but also occurred among women delivered vaginally without known tears.
      CONCLUSION: we suggest that a questionnaire is used 12-18 months after delivery
      to establish the short-time outcome in terms of pelvic floor dysfunction.

PMID- 20798925
TI  - TVT-S in the U position--anatomical study.
AB  - INTRODUCTION AND HYPOTHESIS: The objective is to describe the anatomical position
      of tension-free vaginal tape Secur (TVT-S) in the U position regarding possible
      injury and fixation site. METHODS: We placed TVT-S inserters bilaterally in 13
      embalmed and five fresh frozen female bodies. After dissection, we measured
      distances from the obturator bundle. RESULTS: In embalmed bodies, the mean
      distance of TVT-S from the obturator bundle was 2.83 cm (standard deviation (SD)
      0.87 cm) on the left, 2.92 cm (SD 1.24 cm) on the right. Perforation of the
      fascia of obturator internus muscle occurred in 38.5%. In fresh frozen bodies,
      results were fundamentally similar (p > 0.05). CONCLUSIONS: There is a risk of
      injury to the obturator bundle and urinary bladder during TVT-S; however, there
      is a significant risk of inserting the TVT-S inserter outside the obturator
      internus muscle (into the lesser pelvis). The position of TVT-S does not change
      significantly after legs mal-positioning.

PMID- 20798926
TI  - Vagina, abdominal skin, and aponeurosis: do they have similar biomechanical
      properties?
AB  - INTRODUCTION AND HYPOTHESIS: despite minimal fundamental works, there is an
      increasing use of meshes in urogynecology. The concept is mainly based on
      experiences with abdominal wall surgery. We aimed to compare the biomechanical
      properties of vaginal tissue, abdominal aponeurosis, and skin. METHODS: samples
      from 11 fresh women cadavers without prolapse were collected. Uniaxial tension
      tests were performed and stress-strain curves were obtained. RESULTS:
      biomechanical properties of the vagina, aponeurosis, and skin differed
      significantly. The aponeurosis was much more rigid and less extendible than the
      vagina and skin. Vaginal tissue was less rigid but more extendible than skin.
      There was no difference between the vagina and skin at low strains (p = 0.341),
      but a highly significant difference at large strains (p = 0.005). CONCLUSIONS:
      skin and aponeurosis are not suited to predict vaginal tissue biomechanics. We
      should be cautious when transferring experiences from abdominal wall surgery to
      vaginal reconstructive surgery.

PMID- 20798927
TI  - Childbirth experiences of women with obstetric fistula in Tanzania and Uganda and
      their implications for fistula program development.
AB  - INTRODUCTION AND HYPOTHESIS: authors sought evidence from the testimonies of
      women living with fistula regarding local risk factors for fistula and the impact
      of fistula on women's lives. METHODS: one hundred thirty-seven women recruited
      from health facilities and at the community level in Tanzania and Uganda were
      interviewed using quantitative and qualitative methods, including participatory
      approaches. RESULTS: women of all ages and parities endured fistula. The
      testimonies illustrated that physical, socio-economic and cultural constraints,
      as well as health system failures, led to fistula, and the condition imposed
      harsh consequences on women's lives. Constraints included deficient maternal
      health services and personnel, delays in seeking and accessing care, and limited
      fistula repair services. Women endured severe social stigma and severe economic
      hardships. CONCLUSIONS: participants' testimonies expand current understanding of
      women's experience of fistula and point to recommendations that could improve
      maternal health care, reduce women's risk of fistula, and improve the lives of
      women living with the condition.

PMID- 20798928
TI  - Polymorphisms in the 5' flank of COL1A1 gene and osteoporosis: meta-analysis of
      published studies.
AB  - A meta-analysis of studies was conducted involving 24,511 participants with 7,864
      fractures in which polymorphisms in the 5' flank of COL1A1 (rs1107946, rs2412298,
      and rs1800012) were related to osteoporosis phenotypes. Polymorphisms of all
      three sites were associated with BMD, and rs1800012 was associated with fracture
      but effect sizes were modest. INTRODUCTION AND HYPOTHESIS: Polymorphisms in the
      5' flank of COL1A1 gene have been implicated as genetic markers for
      susceptibility to osteoporosis, but previous studies have yielded conflicting
      results. METHODS: We conducted a meta-analysis of 32 studies including 24,511
      participants and 7,864 fractures in which alleles at the -1997G/T (rs1107946), 
      1663in/delT (rs2412298), and Sp1 binding site polymorphisms (rs1800012) of COL1A1
      had been related to bone mineral density (BMD) or fracture. RESULTS: For the Sp1
      polymorphism, BMD values in TT homozygotes were 0.13 units [95% CI, 0.03 to 0.24]
      lower at the spine (p = 0.01) and 0.16 units [0.10 to 0.23] lower at the hip (p =
      1 x 10-6) than GG homozygotes. Clinical fractures were 1.31-fold [1.04-1.65]
      increased in TT homozygotes (p = 0.02) and vertebral fractures were 1.34-fold
      [1.01-1.77] increased (p = 0.04). We also observed associations between spine BMD
      and allelic variants at the -1997G/T (p = 0.05) and the -1663indelT (p = 0.009)
      sites. We found no association between alleles at the -1997G/T or -1663indelT
      sites and fracture but power was limited. CONCLUSIONS: The COL1A1 Sp1
      polymorphism is associated with a modest reduction in BMD and an increased risk
      of fracture, although we cannot fully exclude the possibility that the results
      may have been influenced by publication bias. Further studies are required to
      fully evaluate the contribution of the -1997G/T and -1663in/delT sites to these
      phenotypes and to determine if they interact with the Sp1 polymorphism to
      regulate susceptibility to osteoporosis.

PMID- 20798929
TI  - Adherence and persistence with teriparatide among patients with commercial,
      Medicare, and Medicaid insurance.
AB  - Adherence to, and persistence with, treatments for osteoporosis are low.
      Adherence with teriparatide decreases over time. Higher copayments in the
      commercial/Medicare population were associated with worse persistence.
      Understanding factors such as prior screening, prior treatment history, and out
      of pocket costs that influence persistence with teriparatide may help clinicians
      make informed decisions. INTRODUCTION: The purpose of this study was to evaluate
      adherence and persistence with teriparatide. METHODS: Beneficiaries with at least
      one claim for teriparatide in 2003 or 2004 and continuous enrollment in the
      previous 12 months and subsequent 6 months were identified in a national
      commercial/Medicare and Medicaid administrative claims database (MarketScan(r)).
      Adherence was assessed through calculation of the medication possession ratio
      (MPR). Persistence was measured by time until discontinuation and time until
      first 60-day gap in treatment. Factors associated with persistence were assessed
      using Cox proportional hazards models. RESULTS: The average MPR at 6 months was
      0.74 (N=2,218) and at 12 months, was 0.66 (N=1,303). At 6 months, 64.6% of
      patients remained on therapy and at 12 months, 56.7% remained. Bone mineral
      density screening and use of antiresorptive therapy within the 12 months pre
      period, and lower patient copayments were associated with increased persistence.
      CONCLUSION: Patients appear to have good adherence with teriparatide over the
      first 6 months which declines over time. Prior screening and treatment of
      osteoporosis and out of pocket costs appear to impact persistence. To optimize
      patient outcomes, clinicians should consider clinical factors that impact
      persistence, while healthcare decision makers should consider the negative effect
      of higher patient copayments on persistence.

PMID- 20798930
TI  - Deoxynivalenol: mechanisms of action, human exposure, and toxicological
      relevance.
AB  - The trichothecene mycotoxin deoxynivalenol (DON) is produced in wheat, barley and
      corn following infestation by the fungus Fusarium in the field and during
      storage. Colloquially known as "vomitoxin" because of its emetic effects in pigs,
      DON has been associated with human gastroenteritis. Since DON is commonly
      detected in cereal foods, there are significant questions regarding the risks of
      acute poisoning and chronic effects posed to persons ingesting this
      trichothecene. A further challenge is how to best manage perceived risks without
      rendering critical food staples unavailable to an ever-expanding world
      population. In experimental animal models, acute DON poisoning causes emesis,
      whereas chronic low-dose exposure elicits anorexia, growth retardation,
      immunotoxicity as well as impaired reproduction and development resulting from
      maternal toxicity. Pathophysiologic effects associated with DON include altered
      neuroendocrine signaling, proinflammatory gene induction, disruption of the
      growth hormone axis, and altered gut integrity. At the cellular level, DON
      induces ribotoxic stress thereby disrupting macromolecule synthesis, cell
      signaling, differentiation, proliferation, and death. There is a need to better
      understand the mechanistic linkages between these early dose-dependent molecular
      effects and relevant pathological sequelae. Epidemiological studies are needed to
      determine if relationships exist between consumption of high DON levels and
      incidence of both gastroenteritis and potential chronic diseases. From the
      perspective of human health translation, a particularly exciting development is
      the availability of biomarkers of exposure (e.g. DON glucuronide) and effect
      (e.g. IGF1) now make it possible to study the relationship between DON
      consumption and growth retardation in susceptible human populations such as
      children and vegetarians. Ultimately, a fusion of basic and translational
      research is needed to validate or refine existing risk assessments and regulatory
      standards for this common mycotoxin.

PMID- 20798931
TI  - Protein analysis of laser capture micro-dissected tissues revealed cell-type
      specific biological functions in developing barley grains.
AB  - Both the nucellar projection (NP) and endosperm transfer cells (ETC) of the
      developing barley grain (harvested 8 days after flowering) were isolated by laser
      capture micro-dissection combined with pressure catapulting. Protein extracts
      were analyzed by nanoUPLC separation combined with ESI-Q-TOF mass spectrometry.
      The majority of the ~160 proteins identified were involved in translation,
      protein synthesis, or protein destination. The NP proteome was enriched for
      stress defense molecules, while proteins involved in assimilate transport and the
      mobilization of nutrients were common to both the NP and the ETC. The combined
      qualitative and quantitative protein profiling allowed for the identification of
      several proteins showing tissue specificity in their expression, which underlines
      the distinct biological functions of these two tissues within the developing
      barley grain.

PMID- 20798932
TI  - Silver nanoparticle-enhanced fluorescence in microtransponder-based immuno- and
      DNA hybridization assays.
AB  - The aim of this study is to improve assay sensitivity in common solid-phase
      bioassay configurations as the result of using silver nanoparticles. The solid
      phase was provided by numerically indexed, silicon-based electronic chips,
      microtransponders (p-Chips) that have previously been used in multiplexed assays.
      Assay configurations investigated included an ELISA-type immunoassay and a DNA
      hybridization assay. The surface of p-Chips was derivatized with the silver
      island film (SIF) and a polymer, and then characterized with AFM and SEM. Silver
      nanoparticle sizes were in the range of 100 to 200 nm. Four fluorophores were
      tested for fluorescence enhancement; namely, green fluorescent protein,
      phycoerythrin, Cy3 and Alexa Fluor 555. We consistently observed significant
      fluorescence enhancement and sensitivity improvement in the p-Chip-based assays:
      the sensitivity in the cytokine IL-6 immunoassay was 4.3 pg/ml, which represented
      a 25-fold increase over the method not involving a SIF; and 50 pM in the
      hybridization assay, a 38-fold increase. The greatest enhancement was obtained
      for p-Chip surfaces derivatized first with the polymer and then coated with SIF.
      In conclusion, we show that the SIF-p-Chip-based platform is a highly sensitive
      method to quantify low-abundance biomolecules in nucleic acid-based assays and
      immunoassays.

PMID- 20798933
TI  - Tandem MS for environmental and food analysis.

PMID- 20798934
TI  - Genes devoid of full-length transposable element insertions are involved in
      development and in the regulation of transcription in human and closely related
      species.
AB  - Transposable elements (TEs) are major components of mammalian genomes, and their
      impact on genome evolution is now well established. In recent years several
      findings have shown that they are associated with the expression level and
      function of genes. In this study, we analyze the relationships between human
      genes and full-length TE copies in terms of three factors (gene function,
      expression level, and selective pressure). We classified human genes according to
      their TE density, and found that TE-free genes are involved in important
      functions such as development, transcription, and the regulation of
      transcription, whereas TE-rich genes are involved in functions such as transport
      and metabolism. This trend is conserved through evolution. We show that this
      could be explained by a stronger selection pressure acting on both the coding and
      non-coding regions of TE-free genes than on those of TE-rich genes. The higher
      level of expression found for TE-rich genes in tumor and immune system tissues
      suggests that TEs play an important role in gene regulation.

PMID- 20798935
TI  - Effect of sodium bicarbonate as a pharmaceutical formulation excipient on the
      interaction of fluvastatin with membrane phospholipids.
AB  - Excipients in the pharmaceutical formulation of oral drugs are notably employed
      to improve drug stability. However, they can affect drug absorption and
      bioavailability. Passive transport through intestinal cell walls is the main
      absorption mechanism of drugs and, thus, involves an interaction with the
      membrane lipids. Therefore in this work, the effect of the excipient NaHCO(3) on
      the interaction of the anticholesterolemic drug fluvastatin sodium (FS) with
      membrane phospholipids was investigated by (1)H NMR and FTIR spectroscopy. Sodium
      bicarbonate is often combined with fluvastatin for oral delivery to prevent its
      degradation. We have used model DMPC/DMPS membranes to mimic the phospholipid
      content of gut cell membranes. The results presented in this work show a 100%
      affinity of FS for the membrane phospholipids that is not modified by the
      presence of the excipient. However, NaHCO(3) is shown to change the interaction
      mechanism of the drug. According to our data, FS enters the DMPC/DMPS bilayer
      interface by interacting with the lipids' polar headgroups and burying its
      aromatic moieties into the apolar core. Moreover, lipid segregation takes place
      between the anionic and zwitterionic lipids in the membranes due to a
      preferential interaction of FS with phosphatidylserines. The excipient
      counteracts this favored interaction without affecting the drug affinity and
      location in the bilayer. This work illustrates that preferential interactions
      with lipids can be involved in passive drug permeation mechanisms and gives
      evidence of a possible nonpassive role of certain excipients in the interaction
      of drugs with membrane lipids.

PMID- 20798936
TI  - Maximizing the native concentration and shelf life of protein: a multiobjective
      optimization to reduce aggregation.
AB  - A multiobjective optimization was performed to maximize native protein
      concentration and shelf life of ASD, using artificial neural network (ANN) and
      genetic algorithm (GA). Optimum pH, storage temperature, concentration of
      protein, and protein stabilizers (Glycerol, NaCl) were determined satisfying the
      twin objective: maximum relative area of the dimer peak (native state) after 48 h
      of storage, and maximum shelf life. The relative area of the dimer peak, obtained
      from size exclusion chromatography performed as per the central composite design
      (CCD), and shelf life (obtained as turbidity change) served as training targets
      for the ANN. The ANN was used to establish mathematical relationship between the
      inputs and targets (from CCD). GA was then used to optimize the above
      determinants of aggregation, maximizing the twin objectives of the network. An
      almost fourfold increase in shelf life (~196 h) was observed at the GA-predicted
      optimum (protein concentration: 6.49 mg/ml, storage temperature: 20.8  degrees C,
      Glycerol: 10.02%, NaCl: 51.65 mM and pH: 8.2). Since no aggregation was observed
      at the optimum till 48 h, all the protein was found at the dimer position with
      maximum relative area (64.49). Predictions of the finally adapted network also
      reveal that storage temperature and solvent glycerol concentration plays key role
      in deciding the degree of ASD aggregation. This multiobjective optimization
      strategy was also successfully applied in minimizing the batch culture period and
      determining optimum combination of medium components required for most economical
      production of actinomycin D.

PMID- 20798937
TI  - Branching patterns of the male internal iliac artery: imaging findings.
AB  - The aim of this study was to establish the imaging findings of the main branching
      patterns of the male internal iliac arteries, using different imaging modalities
      (angio MR, angio CT and digital angiography). Twenty-one males (mean age 73.2
      years) underwent imaging evaluation with angio MR, angio CT and digital
      angiography to define the internal iliac artery anatomy before selective
      embolization of the pelvic arteries. All three modalities were used in 3
      patients, angio MR and digital angiography in 17 patients, angio CT and digital
      angiography in 6 patients and only angio CT in 1 patient. Internal iliac arteries
      were classified into four groups using the Yamaki classification (modified from
      the Adachi's classification). Twenty-six pelvic sides were classified as Group A
      (61.9%), 13 as Group B (31%) and 3 as Group C (7.1%) with no cases of Group D
      found. Angio MR, angio CT and digital angiography were able to detect most
      branches of the internal iliac artery. Group A was the most frequent internal
      iliac artery branching pattern. Angio CT showed better detailed anatomy than
      angio MR and digital angiography was considered the gold-standard. Non-invasive
      vascular imaging with angio MR or angio CT is essential before invasive
      interventions, allowing better planning of the procedure.

PMID- 20798938
TI  - Effect of Q-angle on patellar positioning and thickness of knee articular
      cartilages.
AB  - The purpose of the present study was to investigate whether an increased
      quadriceps angle (Q-angle) has an effect on patellar positioning and/or the
      thickness of the medial and lateral tibiofemoral and patellofemoral articular
      cartilage and menisci, in a group of young asymptomatic individuals. These
      individuals were detected in a previous study with a decreased anatomical cross
      sectional area of the vastus medialis and lateralis as a result of an increased Q
      angle. Patellar positioning and the thickness of the articular cartilages were
      determined in 19 asymptomatic male individuals with high Q-angle (HQ-angle) (18.5
      degrees  +/- 2.6 degrees ) using magnetic resonance imaging (MRI). Seventeen male
      counterparts with low Q-angle (10.1 degrees  +/- 1.9 degrees ) were used for
      comparison. The position of the patella was determined by measuring the sulcus
      angle, the lateral patella tilt, the patella-lateral condyle index and the bisect
      offset (BSO) with the quadriceps relaxed. The BSO, was also measured with the
      quadriceps under maximum isometric voluntary contraction. The thickness of the
      articular cartilages of the lateral and medial femoral condyles, the tibial
      condyles, the patellar facets and the menisci were also measured. Our data
      revealed that healthy individuals with HQ-angle are unlikely to demonstrate any
      changes in the position of the patella and/or the thickness of the knee articular
      cartilages. The decreased anatomical area of the vastus medialis and an almost
      equally atrophied vastus lateralis, which was previously observed in this group
      of individuals may prevent in part the misalignment of the patella and early wear
      of the tibiofemoral and patellofemoral articular cartilages.

PMID- 20798939
TI  - NCT01110291: induction of CYP3A activity and lowered exposure to docetaxel in
      patients with primary breast cancer.
AB  - PURPOSE: To study the CYP3A activity before and after docetaxel administration.
      Furthermore, it was investigated whether peroral midazolam could predict
      docetaxel exposure and adverse events. METHODS: Twenty patients with primary high
      risk breast cancer were given docetaxel as a 1-h infusion 80 mg/m(2) in a 21-day
      cycle in 3 cycles followed by 3 cycles of cyclophosphamide, epirubicin and
      fluorouracil. CYP3A activity was assessed a day before and a day after docetaxel
      by 7.5 mg oral midazolam. All patients were given peroral dexamethasone a total
      dose of 45 mg, of which 15 mg was given before docetaxel infusion and 30 mg
      before the latter assessment of CYP3A activity. All except one patient were given
      11-19 mg of intravenous dexamethasone before docetaxel infusion. RESULTS: CYP3A
      activity was clearly induced when assessed a day after docetaxel administration
      as shown by lower midazolam AUC (P < 0.0001) and higher AUC ratio (1-OH
      midazolam/midazolam, P = 0.018). The mean docetaxel AUC was about a half of that
      previously reported in the literature. Incidence of febrile neutropenia was
      smaller (15%) than reported in literature with comparable docetaxel doses and
      seemed to associate with slower metabolism. No correlation between
      pharmacokinetics of midazolam and docetaxel was found at baseline. CONCLUSIONS:
      We show here a markedly reduced docetaxel exposure followed by CYP3A induction
      by, most likely, dexamethasone. Peroral midazolam seemed not to predict docetaxel
      exposure. Slow CYP3A-mediated metabolism might predispose patients to adverse
      events of docetaxel.

PMID- 20798941
TI  - [Current models of thrombopoiesis].
AB  - Platelets are essential corpuscular blood components required for hemostasis.
      They are released from precursor cells in the bone marrow by cellular
      fragmentation into the blood stream. Although some aspects of platelet biogenesis
      are well known, studying its occurrence in vivo has been mostly unsatisfactory.
      This article reviews some recent findings: It first introduces current models of
      thrombopoiesis including open questions on cell biology. Second, it presents
      current findings on the release of megakaryocytes over the endothelial barrier
      into the blood stream where platelet production takes place outside the bone
      marrow. Finally, it reports on the translation of the more basic science into an
      improved understanding of novel parameters from automated blood counters
      surveying platelet volume (MPV), distribution width (PDW), mass (PCT) and the
      immature platelet fraction (IPF) into clinics where platelet counts are often the
      only accessible parameter to evaluate the risk of bleeding. Combining the
      comprehension of these parameters with a more refined image of how and where
      platelets are born might help find the cause and best therapy when platelet
      counts are low.

PMID- 20798940
TI  - Drosophila as a model system to study autophagy.
AB  - Originally identified as a response to starvation in yeast, autophagy is now
      understood to fulfill a variety of roles in higher eukaryotes, from the
      maintenance of cellular homeostasis to the cellular response to stress,
      starvation, and infection. Although genetics and biochemical studies in yeast
      have identified many components involved in autophagy, the findings that some of
      the essential components of the yeast pathway are missing in higher organisms
      underscore the need to study autophagy in more complex systems. This review
      focuses on the use of the fruitfly, Drosophila melanogaster as a model system for
      analysis of autophagy. Drosophila is an organism well-suited for genetic analysis
      and represents an intermediate between yeast and mammals with respect to
      conservation of the autophagy machinery. Furthermore, the complex biology and
      physiology of Drosophila presents an opportunity to model human diseases in a
      tissue specific and analogous context.

PMID- 20798943
TI  - [Characterisation of DNA methylation biomarkers for bladder cancer].
AB  - Despite considerable advances in recent years in our understanding of the genetic
      changes occurring in urinary bladder cancer, similar progress in the field of
      epigenetics has hitherto been lacking. Increasingly, however, focus has shifted
      in the direction of aberrant DNA methylation as a result of recent studies
      showing the direct impact of such promoter hypermethylation on the loss of tumor
      suppressor gene expression and function, therefore potentially affecting tumor
      genesis and progression. The purpose of this study is the identification and
      characterization of new DNA methylation markers in urinary bladder cancer, with
      the expectation that these markers could then be incorporated in a multi-gene
      panel for clinical use in early cancer detection. In addition, better
      understanding of the signalling pathways involved will undoubtedly impact the
      development of new treatment strategies. Potential candidate genes, including the
      Wnt antagonist SFRP5 among others, will be validated by different epigenetic
      techniques using invasive and superficial urothelial cell lines as well as tumor
      and urine samples from bladder cancer patients.

PMID- 20798944
TI  - [Dangerous liaisons in prostate cancer. Clinical and biological implications of
      recurrent gene fusions].
AB  - Prostate cancer is a common and clinically heterogeneous disease. Understanding
      the biology of prostate cancer is necessary to best determinate the risk of
      disease progression and develop novel therapeutic approaches to prevent or slow
      down disease progression. The recent discovery and subsequent characterization of
      recurrent gene rearrangements of ETS genes - most frequently ERG - in the
      majority of prostate cancers is a milestone in translational prostate cancer
      research. Although multiple molecular alterations have been detected in prostate
      cancer, a detailed understanding of gene fusion in prostate cancer should help
      explain the clinical and biologic diversity in addition to providing a rationale
      for a molecular sub-classification of the disease. This review describes the path
      from the identification of common ETS gene rearrangements in prostate cancer to
      possible applications in the treatment of patients, on to the potential
      scientific implications arising from their discovery.

PMID- 20798945
TI  - [The current TNM system for gastrointestinal tumors part II].
AB  - Entirely new classifications are those for gastrointestinal stromal tumours,
      gastrointestinal neuroendocrine tumours, intrahepatic cholangiocarcinoma and
      perihilar extrahepatic bile duct carcinomas. Major and praxis-relevant
      alterations concern colorectal tumours and include new classifications of
      carcinomas and carcinoids of the appendix. Minor alterations are seen in the
      classification of hepatocellular carcinomas. No changes were made for tumours of
      the anal canal, the gallbladder (excluding the inclusion of tumours of the cystic
      duct) and tumours of the pancreas and the ampulla of Vater.

PMID- 20798946
TI  - Clinical features and hyperferritinemia diagnostic cutoff points for AOSD based
      on ROC curve: a Chinese experience.
AB  - Hyperferritinemia has been reported in adult-onset Still's disease (AOSD). This
      study aims to investigate clinical features of AOSD in Chinese population and
      diagnostic value of different hyperferritinemia cutoff points based on ROC curve.
      A total of 48 patients from October 2002 to February 2007 diagnosed AOSD in the
      department of rheumatology, the first affiliated hospital of Sun Yat-set
      University were enrolled. A total of 86 patients mainly complaining fever >39
      degrees C for over one week and meeting Yamaguchi criteria but confirmed as non
      AOSD by other serological or pathological tests were obtained from the same
      department as controls. Total serum ferritin levels were determined at the time
      of admission. Clinical features of AOSD in Chinese population were similar to
      previous studies. Significantly higher levels of total serum ferritin were
      presented in patients with AOSD (8100.7 +/- 13678.5) compared with non-AOSD
      controls (448.3 +/- 539.4) (P < 0.01). No differences were found in serum
      ferritin level between different categories of non-AOSD patients (P > 0.05). High
      value of area under receiver operating characteristic curve (ROC curve) suggested
      that ferritin was very predictive in AOSD diagnosis. Three cutoff points were
      picked based on clinical practice and ROC curve. Ferritin level >=2,500 ug/L
      appeared to be highly specific for a diagnosis of AOSD, yet the low sensitivity
      may falsely ruled out patients with true AOSD. Hyperferritinemia >=750 ug/L was
      seldom observed in inflammatory diseases or solid tumor. Hyperferritinemia
      >=1,250 ug/L could mostly rule out other autoimmune diseases and hematologic
      diseases. Combined Yamaguchi criteria and hyperferritinemia gave better
      prediction for AOSD. In conclusion, different hyperferritinemia cutoff points
      observed in ROC curve help to optimize diagnostic and therapeutic strategy.

PMID- 20798947
TI  - [Minimally invasive angle surgery. The Trabectome].
AB  - The Trabectome provides a new perspective in angle surgery for open angle
      glaucoma. Through a 1.7 mm clear cornea tunnel, the juxtacanalicular meshwork is
      electroablated under gonioscopic control. Thereby, the collector channels in the
      outer wall of Schlemm's canal are uncovered and resistance to trabecular outflow
      is removed. From the literature and from our own experience, a pressure reduction
      by 30-35% can be achieved with a simultaneous reduction of eye drops by 50%. The
      Trabectome can conveniently be combined with phako-emulsification. Serious
      complications have not yet been reported. As the conjunctiva remains completely
      untouched, trabeculectomy, if necessary, could be performed without prognostic
      restrictions. With a realistic target pressure of approximately 16 mmHg,
      Trabectome surgery is indicated in patients with moderate optic nerve damage.

PMID- 20798948
TI  - [Eye and pregnancy.].
AB  - Pregnancy may cause ocular changes, for example refractive changes or contact
      lens intolerance. A number of ocular diseases may deteriorate. Especially
      preexisting diabetic retinopathy may worsen. Vaginal delivery is nearly always
      possible. Caesarean section is not required due to myopia, peripheral retinal
      degenerations or after retinal surgery. Most topically applied drugs usually used
      in ophthalmology are safe during pregnancy.

PMID- 20798950
TI  - Radionuclide transfer to marine biota species: review of Russian language
      studies.
AB  - An extensive programme of experiments on transfer of radionuclides to aquatic
      species was conducted in the former USSR starting from the early 1950s. Only a
      few of these studies were made available in the English language literature or
      taken into account in international reviews of radionuclide behaviour in marine
      ecosystems. Therefore, an overview of original information on radionuclide
      transfer to marine biota species available from Russian language literature
      sources is presented here. The concentration ratio (CR) values for many
      radionuclides and for marine species such as: (239)Pu, (106)Ru and (95)Zr
      (crustacean), (54)Mn, (90)Sr, (95)Nb, (106)Ru, (137)Cs (239)Pu, (241)Am and
      natural U (molluscs), and (54)Mn, (90)Sr, (137)Cs and (144)Ce (fish) are in good
      agreement with those previously published, whilst for some of them, in
      particular, for (32)P and (110)Ag (crustaceans), (35)S (molluscs), (32)P, (35)S,
      (95)Nb, and (106)Ru (macroalgae) and (60)Co and (239,240)Pu (fish) the data
      presented here suggest that changes in the default CR reference values presented
      in recent marine reviews may be required. The data presented here are intended to
      supplement substantially the CR values being collated within the handbook on
      Wildlife Transfer Coefficients, coordinated under the IAEA EMRAS II programme.

PMID- 20798949
TI  - [Juvenile arthritides].
AB  - Arthritis in children represents a diagnostic and therapeutic challenge. The
      diagnostic spectrum is broad and a very precise indication for diagnostic and
      therapeutic procedures, especially in small children, is important. In addition
      to acute arthritides - viral arthritis, reactive arthritis, Lyme arthritis and
      septic arthritis - secondary chronic arthritis related to an underlying disease
      as well as juvenile idiopathic arthritis (JIA), the most common chronic
      inflammatory systemic disease in children, need to be considered. This overview
      is a guide to the diagnosis of arthritis in childhood and to evidence-based
      therapy of JIA in particular. This consists of a combination of nonsteroidal anti
      inflammatory drugs, systemic and intraarticular corticosteroids, traditional
      DMARDs such as sulfasalazine, methotrexate and leflunomide, the TNF inhibitors
      etanercept, adalimumab and, with restrictions, infliximab, other
      biopharmaceuticals such as anakinra, canakinumab and rilonacept, and tocilizumab
      and finally, abatacept.

PMID- 20798951
TI  - Demonstration of striatopallidal iron deposition in chorea-acanthocytosis by
      susceptibility-weighted imaging.

PMID- 20798952
TI  - Pure alexia caused by separate lesions of the splenium and optic radiation.
AB  - Pure alexia is severe difficulty in reading and understanding written language
      but with normal oral language and writing abilities. We report a patient with
      pure alexia caused by two different infarct lesions in the left lateral thalamus
      and the left splenium of the corpus callosum. A 56-year-old right-handed man was
      admitted to hospital with right homonymous hemianopia associated with pure
      alexia. He could write kana characters but not kanji. His cranial magnetic
      resonance imaging revealed two different infarct lesions in the left optic
      radiation and the left splenium of the corpus callosum. Magnetic resonance
      angiography showed mild stenosis at the origin of the right vertebral artery and
      stenosis of the left distal posterior cerebral artery. The mechanism of
      developing pure alexia can be simply explained by disconnection. We assumed that
      agraphia of kanji was caused by the effect of ischemia and edema following
      transient obstruction in branches from the distal posterior cerebral artery.

PMID- 20798953
TI  - Molecular diagnosis of known recessive ataxias by homozygosity mapping with SNP
      arrays.
AB  - The diagnosis of rare inherited diseases is becoming more and more complex as an
      increasing number of clinical conditions appear to be genetically heterogeneous.
      Multigenic inheritance also applies to the autosomal recessive progressive
      cerebellar ataxias (ARCAs), for which 14 genes have been identified and more are
      expected to be discovered. We used homozygosity mapping as a guide for
      identification of the defective locus in patients with ARCA born from
      consanguineous parents. Patients from 97 families were analyzed with GeneChip
      Mapping 10K or 50K SNP Affymetrix microarrays. We identified six families
      homozygous for regions containing the autosomal recessive spastic ataxia of
      Charlevoix-Saguenay (ARSACS) gene, two families homozygous for the ataxia
      telangiectasia gene (ATM), two families homozygous for the ataxia with oculomotor
      apraxia type 1 (AOA1) gene, and one family homozygous for the AOA type 2 (AOA2)
      gene. Upon direct gene testing, we were able to identify a disease-related
      mutation in all families but one of the two kindred homozygous at the ATM locus.
      Although linkage analyses pointed to a single locus on chromosome 11q22.1-q23.1
      for this family, clinical features, normal levels of serum alpha-foetoprotein as
      well as absence of mutations in the ATM gene rather suggest the existence of an
      additional ARCA-related gene in that interval. While the use of homozygosity
      mapping was very effective at pointing to the correct gene, it also suggests that
      the majority of patients harbor mutations either in the genes of the rare forms
      of ARCA or in genes yet to be identified.

PMID- 20798954
TI  - Fyodorov-Zuev keratoprosthesis implantation: long-term results in patients with
      multiple failed corneal grafts.
AB  - BACKGROUND: The long term results of the Fyodorov-Zuev keratoprosthesis are
      presented for ten patients with repeated graft failures. METHODS: The study took
      place at Dr Khodadoust Eye Hospital. The Fyodorov-Zuev keratoprosthesis was
      implanted in ten patients with repeated graft failures, including seven patients
      with old trachoma, two patients with chemical injury, and a patient with thermal
      injury. The outcome measures were visual acuity, retention, and complications of
      the keratoprosthesis. RESULTS: Preoperative best-uncorrected visual acuity (BUVA)
      ranged from counting fingers to light perception (median: light perception). The
      keratoprosthesis dramatically improved vision in most patients. Patients retained
      BUVA of 20/200-20/50 in 50%, 20/60-20/100 in 30%, 20/200 in 10% and 20/400 in
      10%. Overall, 90% had 1 year postoperative vision of 20/200 or better. 70% of
      cases had BUVA of 20/200 or better at the last follow-up (average 52 months). Of
      ten keratoprosthesis implanted, three have been removed, and as a result,
      retention rate was 70% during average follow-up of 52 months .The most common
      postoperative complications were retroprosthetic membrane formation (40%),
      uveitis (20%), glaucoma (20%), tissue overgrowth (20%), early leakage (20%), late
      leakage (20%), aseptic necrosis (20%), retinal detachment (10%), endophthalmitis
      (10%), and granulation tissue growth (10%). CONCLUSIONS: Fyodorov-Zuev
      keratoprosthesis is an effective means of managing repeated corneal graft
      failure.

PMID- 20798955
TI  - Two-digit number processing: holistic, decomposed or hybrid? A computational
      modelling approach.
AB  - Currently, there are three competing theoretical accounts concerning the nature
      of two-digit number magnitude representation: a holistic, a strictly decomposed,
      and a hybrid model. Observation of the unit-decade compatibility effect (Nuerk et
      al. in Cognition 82:B25-B33, 2001) challenged the view of two-digit number
      magnitude to be represented as one integrated entity. However, at the moment
      there is no study distinguishing between the decomposed and the hybrid model. The
      present study addressed this issue using a computational modelling approach.
      Three network models complying with the constraints of all three theoretical
      models were programmed and trained on two-digit number comparison. Models were
      compared as to how well they accounted for empirical effects in the most
      parsimonious way. Generally, this evaluation indicated that the empirical data
      were simulated best by the strictly decomposed model. Implications of these
      results for our understanding of the nature of human number magnitude
      representation are discussed.

PMID- 20798956
TI  - TIMP-1 interaction with alphavbeta3 integrin confers resistance to human
      osteosarcoma cell line MG-63 against TNF-alpha-induced apoptosis.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine affecting
      diverse cellular responses. TNF-alpha is cytotoxic in many systems, but it can
      also act as an anti-apoptotic signal to promote cell survival pathways activated
      through integrins and extracellular matrix components. This is particularly
      evident in cancer cells. To unravel the basis of resistance to TNF-alpha-induced
      apoptosis, human osteosarcoma MG-63 cell line was used. Our data showed that
      resistance to apoptosis was accompanied by high levels of TIMP-1 expression in
      part mediated by NF-kappaB activation, whereas under apoptotic conditions, in the
      presence of cycloheximide (CHX), TIMP-1 and alphavbeta3 integrin protein levels
      were significantly reduced. Silencing TIMP-1 using siRNA led to increased
      apoptosis following treatment with TNF-alpha, whereas exogenously-added
      recombinant TIMP-1 reduced the extent of apoptosis. Immunoprecipitation and
      confocal microscopy experiments demonstrated that TIMP-1 interacted with
      alphavbeta3 integrins. The biological role of this interaction was revealed by
      the use of echistatin, an antagonist of alphavbeta3 integrin. In the presence of
      echistatin, decreased protection against apoptosis by recombinant TIMP-1 was
      observed.

PMID- 20798957
TI  - Genetics of congenital anomalies of the kidney and urinary tract.
AB  - Congenital anomalies of the kidney and urinary tract (CAKUT) occur in 1 in 500
      births and are a major cause of morbidity in children. Notably, CAKUT account for
      the most cases of pediatric end-stage renal disease and predispose the individual
      to hypertension and cardiovascular disease throughout life. Although some forms
      of CAKUT are a part of a syndrome or are associated with a positive family
      history, most cases of renal system anomalies are sporadic and isolated to the
      urinary tract. Broad phenotypic spectrum of CAKUT and variability in genotype
      phenotype correlation indicate that pathogenesis of CAKUT is a complex process
      that depends on interplay of many factors. This review focuses on the genetic
      mechanisms (single-gene mutations, modifier genes) leading to renal system
      anomalies in humans and discusses emerging insights into the role of epigenetics,
      in utero environmental factors, and micro-RNAs (miRNAs) in the pathogenesis of
      CAKUT. Common gene networks that function in defined temporospatial fashion to
      orchestrate renal system morphogenesis are highlighted. Derangements in cellular,
      molecular, and morphogenetic mechanisms that direct normal renal system
      development are emphasized as a major cause of CAKUT. Integrated understanding of
      how morphogenetic process disruptions are linked to CAKUT will enable improved
      diagnosis, treatment, and prevention of congenital renal system anomalies and
      their consequences.

PMID- 20798958
TI  - The renin-angiotensin system and hypertension in autosomal recessive polycystic
      kidney disease.
AB  - Hypertension is a well-recognized complication of autosomal recessive polycystic
      kidney disease (ARPKD). The renin-angiotensin system (RAS) is a key regulator of
      blood pressure; however, data on the RAS in ARPKD are limited and conflicting,
      showing both up- and down-regulation. In the current study, we characterized
      intrarenal and systemic RAS activation in relationship to hypertension and
      progressive cystic kidney disease in the ARPKD orthologous polycystic kidney
      (PCK) rat. Clinical and histological measures of kidney disease, kidney RAS gene
      expression by quantitative real-time PCR, angiotensin II (Ang II)
      immunohistochemistry, and systemic Ang I and II levels were assessed in 2-, 4-,
      and 6-month-old cystic PCK and age-matched normal rats. PCK rats developed
      hypertension and progressive cystic kidney disease without significant worsening
      of renal function or relative kidney size. Intrarenal renin, ACE and Ang II
      expression was increased significantly in cystic kidneys; angiotensinogen and Ang
      II Type I receptor were unchanged. Systemic Ang I and II levels did not differ.
      This study demonstrates that intrarenal, but not systemic, RAS activation is a
      prominent feature of ARPKD. These findings help reconcile previous conflicting
      reports and suggest that intrarenal renin and ACE gene upregulation may represent
      a novel mechanism for hypertension development or exacerbation in ARPKD.

PMID- 20798960
TI  - Examination of couples' attachment security in relation to depression and
      hopelessness in maritally distressed patients facing end-stage cancer and their
      spouse caregivers: a buffer or facilitator of psychosocial distress?
AB  - PURPOSE: The purpose of this study is to determine levels of depression and
      hopelessness and to explore the relationship between attachment security and
      psychosocial distress in patients with metastatic/recurrent cancer and spouse
      caregivers, experiencing marital distress. METHODS: Couple-participants were from
      a pilot study and a larger clinical trial prior to randomization. Participation
      required that one partner endorsed marital distress on the Revised Dyadic
      Adjustment Scale (RDAS). Outcome measures included the Beck Depression Inventory
      II (BDI-II), Beck Hopelessness Scale (BHS), and Experiences in Close
      Relationships Inventory. RESULTS: Caregivers, compared with their matched ill
      partners, had significantly higher scores on the RDAS (<distress) after taking
      sex, avoidance, and anxiety into account. Fifty-two percent of patients and 33%
      of caregivers scored above the BDI-II cut-off (>= 15) for depression, with
      patients and females reporting higher levels of depression compared to caregivers
      and males. Thirty-three percent of patients and 24% of caregivers scored above
      the BHS cut-off (>= 8) for hopelessness, with males and patients displaying
      significantly higher mean scores compared with females and caregivers. There was
      a significant interaction effect of sex and avoidance for RDAS; as the male
      avoidance subscale score increased, the female caregiver RDAS declined
      (>distressed). CONCLUSIONS: Marital distress may be amplified within insecure
      attachment bonds, especially among avoidant male patients and their female
      caregivers, which may influence caregiving/care-receiving. We offer unique,
      preliminary support for identifying couples at risk to help reduce suffering and
      complicated bereavement in the terminal cancer population. Further research that
      include larger studies, are needed to determine relationships among attachment
      and psychosocial outcomes.

PMID- 20798959
TI  - [Predictors of chronic pain following surgery. What do we know?].
AB  - Chronic postoperative pain is known to be a significant clinical and economic
      problem. The estimated mean incidence is high and varies between 10 and 50%, with
      variations mostly related to procedure-specific conditions. High-risk types of
      surgeries are e.g. thoracotomy, breast or inguinal hernia surgery and
      amputations. Although there is increasing knowledge about the incidence of
      chronic postoperative pain after certain types of surgical procedures, there are
      only limited data related to the mechanisms and pathophysiology leading to
      chronic pain after surgery. Neuropathic pain components have been discussed,
      especially following operations with a high incidence of nerve damage (for
      example axillary lymphadenectomy). Besides surgical factors it seems that there
      are a number of other factors which likely increase the risk of chronic
      postoperative pain. These predictors for the development of chronic postoperative
      pain are multiple and include individual genetic factors, age and sex of the
      individual patient, preoperative chronic pain, psychosocial factors,
      neurophysiological factors, intraoperative nerve and muscle damage, postoperative
      complications and acute pain in the early postoperative period. Quantitative
      sensory testing including tests of inhibitory circuits like DNIC might help to
      predict the risk of individual patients even before surgery has started. The
      perioperative identification of patients who are at high risk for developing
      chronic pain after surgery is therefore a major goal for the future. This may
      help to develop preventive treatment strategies and avoid treatments with side
      effects for patients who are not at risk for developing chronic pain after
      surgery. Due to a lack of appropriate data for sufficient preventive approaches
      an effective postoperative acute pain management and a nerve-conserving surgical
      technique are the major keys in the prophylaxis of chronic postoperative pain.

PMID- 20798961
TI  - Expert's comment concerning grand rounds case entitled "surgical treatment of a
      180 degrees  thoracolumbar fixed kyphosis in a young achondroplastic patient: a
      one stage 'in situ' combined fusion and spinal cord translocation" (by J. C.
      Auregan, T. Odent, M. Zerah, J.-P. Padovani and C. Glorion).
AB  - An expert comment is provided for the case of an 18-year-old male achondroplastic
      patient with a severe thoracolumbar kyphosis and spinal stenosis managed with a
      five level hemilaminotomy, a decancellation osteotomy of the three apical
      vertebrae and circumferential fusion. A review incidence, presenting symptoms and
      treatment options for thoracolumbar kyphosis in adults with achondroplasia, is
      provided.

PMID- 20798962
TI  - Comparative validity of the WHO-5 Well-Being Index and two-question instrument
      for screening depressive symptoms in patients with type 2 diabetes.
AB  - A simple tool consisting of two questions for screening depressive symptoms has
      been shown to be useful in primary care settings, but its validity in patients
      with diabetes has yet to be evaluated. We compared the test performance of this
      two-question instrument with that of WHO (The World Health Organization)-5. We
      consecutively enrolled 153 patients with type 2 diabetes who visited a diabetes
      clinic in Japan. Using the Center for Epidemiologic Studies Depression Scale as a
      reference standard of depressive symptoms, we calculated the sensitivity and
      specificity of the two-question instrument and WHO-5, and compared the area under
      the ROC curves of these tests. The two-question instrument had a sensitivity of
      53.6% (95% CI, 39.7-67.0%) and specificity of 67.7% (95% CI, 58.1-74.9%). With
      the conventional cutoff point equal to or less than 13 points, the WHO-5 had a
      sensitivity of 57.1% (95% CI, 43.2-70.3%) and specificity of 82.5% (95% CI, 81.9
      94.9%). The area under the ROC curve for the WHO-5 and two-item questionnaire, an
      indicator of discriminatory power, was 0.81 and 0.73, respectively, showing a
      statistically significant difference (P = 0.0453). The two-question instrument
      had statistically lower discriminatory power than the WHO-5 in screening
      depressive symptoms in patients with diabetes. We do not recommend the use of the
      two-question instrument for screening depressive symptoms in patients with
      diabetes.

PMID- 20798963
TI  - Encephalopathies: the emerging diabetic complications.
AB  - Diabetic encephalopathies are now accepted complications of diabetes. They appear
      to differ in type 1 and type 2 diabetes as to underlying mechanisms and the
      nature of resulting cognitive deficits. The increased incidence of Alzheimer's
      disease in type 2 diabetes is associated with insulin resistance,
      hyperinsulinemia and hyperglycemia, and commonly accompanying attributes such as
      hypercholesterolemia, hypertension and obesity. The relevance of these disorders
      as to the emergence of dementia and Alzheimer's disease is discussed based on
      epidemiological studies. The pathobiology of accumulation of beta-amyloid and tau
      the hallmarks of Alzheimer's disease are discussed based on experimental data.
      Type 1 diabetic encephalopathy is likely to increase as a result of the global
      increase in the incidence of type 1 diabetes and its occurrence in increasingly
      younger patients. Alzheimer-like changes and dementia are not prominently
      increased in type 1 diabetes. Instead, the type 1 diabetic encephalopathy
      involves learning abilities, intelligence development and memory retrieval
      resulting in impaired school and professional performances. The major underlying
      component here appears to be insulin deficiency with downstream effects on the
      expression of neurotrophic factors, neurotransmitters, oxidative and apoptotic
      stressors resulting in defects in neuronal integrity, connectivity and loss
      commonly occurring in the still developing brain. Recent experimental data
      emphasize the role of impaired central insulin action and provide information as
      to potential therapies. Therefore, the underlying mechanisms resulting in
      diabetic encephalopathies are complex and appear to differ between the two types
      of diabetes. Major headway has been made in our understanding of their
      pathobiology; however, many questions remain to be clarified. In view of the
      increasing incidence of both type 1 and type 2 diabetes, intensified
      investigations are called for to expand our understanding of these complications
      and to find therapeutic means by which these disastrous consequences can be
      prevented and modified.

PMID- 20798964
TI  - Change in the expression of myelination/oligodendrocyte-related genes during
      puberty in the rat brain.
AB  - Age-dependent changes of gene expression in the prefrontal cortex (PFC) of rats
      around the time of puberty were investigated by means of microarray and
      quantitative polymerase chain reaction (qPCR). About 127 and 138 genes were
      increased and decreased, respectively, in the PFC of rats at post-puberty (PD56)
      compared with those at pre-puberty (PD35). Functional analysis showed significant
      associations of these genes with aging, cellular development, and
      neuropsychological disorders. qPCR analysis confirmed down-regulation of seven
      genes related to myelination. As these genes have been reported to be diminished
      in the brain of patients with schizophrenia, the results of this study suggest an
      exaggerated maturation process may contribute to the pathogenesis of psychotic
      disorders.

PMID- 20798965
TI  - Augmented O-GlcNAc signaling attenuates oxidative stress and calcium overload in
      cardiomyocytes.
AB  - O-linked beta-N-acetylglucosamine (O-GlcNAc) is an inducible, dynamically cycling
      and reversible post-translational modification of Ser/Thr residues of
      nucleocytoplasmic and mitochondrial proteins. We recently discovered that O
      GlcNAcylation confers cytoprotection in the heart via attenuating the formation
      of mitochondrial permeability transition pore (mPTP) and the subsequent loss of
      mitochondrial membrane potential. Because Ca(2+) overload and reactive oxygen
      species (ROS) generation are prominent features of post-ischemic injury and favor
      mPTP formation, we ascertained whether O-GlcNAcylation mitigates mPTP formation
      via its effects on Ca(2+) overload and ROS generation. Subjecting neonatal rat
      cardiac myocytes (NRCMs, n >= 6 per group) to hypoxia, or mice (n >= 4 per group)
      to myocardial ischemia reduced O-GlcNAcylation, which later increased during
      reoxygenation/reperfusion. NRCMs (n >= 4 per group) infected with an adenovirus
      carrying nothing (control), adenoviral O-GlcNAc transferase (adds O-GlcNAc to
      proteins, AdOGT), adenoviral O-GlcNAcase (removes O-GlcNAc to proteins, AdOGA),
      vehicle or PUGNAc (blocks OGA; increases O-GlcNAc levels) were subjected to
      hypoxia-reoxygenation or H(2)O(2), and changes in Ca(2+) levels (via Fluo-4AM and
      Rhod-2AM), ROS (via DCF) and mPTP formation (via calcein-MitoTracker Red
      colocalization) were assessed using time-lapse fluorescence microscopy. Both OGT
      and OGA overexpression did not significantly (P > 0.05) alter baseline Ca(2+) or
      ROS levels. However, AdOGT significantly (P < 0.05) attenuated both hypoxia and
      oxidative stress-induced Ca(2+) overload and ROS generation. Additionally, OGA
      inhibition mitigated both H(2)O(2)-induced Ca(2+) overload and ROS generation.
      Although AdOGA exacerbated both hypoxia and H(2)O(2)-induced ROS generation, it
      had no effect on H(2)O(2)-induced Ca(2+) overload. We conclude that inhibition of
      Ca(2+) overload and ROS generation (inducers of mPTP) might be one mechanism
      through which O-GlcNAcylation reduces ischemia/hypoxia-mediated mPTP formation.

PMID- 20798967
TI  - Phosphate ester cleavage promoted by a tetrameric iron(III) complex.
AB  - The purple acid phosphatases (PAPs) are the only binuclear metallohydrolases
      where the necessity for a heterovalent active site [Fe(III)-M(II) (M is Fe, Zn or
      Mn)] for catalysis has been established. The paradigm for the construction of PAP
      biomimetics, both structural and functional, is that the ligands possess
      characteristics which mimic those of the donor sites of the metalloenzyme and
      permit discrimination between trivalent and divalent metal ions. The donor atom
      set of the ligand 2-((2-hydroxy-5-methyl-3-((pyridin-2
      ylmethylamino)methyl)benzyl)(2-hydroxybenzyl)amino)acetic acid (H(3)HPBA) mimics
      that of the active site of PAP although the iron(III) complex of this ligand has
      been characterized as the tetramer [Fe(4)(HPBA)(2)(MU-CH(3)COO)(2)(MU-O)(MU
      OH)(OH(2))(2)]ClO(4).5H(2)O. The phosphoesterase-like activity of the complex in
      1:1 acetonitrile/water has now been investigated using the substrate 2,4
      bis(dinitrophenyl)phosphate. The pH dependence of the catalytic rate revealed a
      non-symmetric bell-shaped profile, with a finite but non-zero rate at high pH.
      Unlike the traditional approach usually employed to analyse these bell-shaped
      profiles, the approach used here involved incorporating additional species which
      contribute to the overall activity. Employing this approach, we show that the
      complex has a k (cat) of 1.6 (+/-0.2) * 10(-3) s(-1), three kinetically relevant
      pK (a) values of 5.3, 6.2 and 8.4, with K (M) of 7.4 +/- 0.6 mM. The kinetic
      parameters are similar to those reported for heterovalent PAP biomimetics.
      Additionally, it is observed that, unlike the enzyme, the oxidation state is not
      the determining factor for catalytic activity.

PMID- 20798968
TI  - Oxygen cost of treadmill and over-ground walking in mildly disabled persons with
      multiple sclerosis.
AB  - Walking impairment is a ubiquitous feature of multiple sclerosis (MS) and the
      O(2) cost of walking might quantify this dysfunction in mild MS. This paper
      examined the difference in O(2) cost of walking between persons with MS who have
      mild disability and healthy controls and the correlation between the O(2) cost of
      walking and disability. Study 1 included 18 persons with mild MS and 18 controls
      and indicated that the O(2) cost of walking was significantly higher in MS than
      controls and that disability was significantly associated with the O(2) cost of
      slow, moderate, and fast treadmill walking. Study 2 included 24 persons with mild
      MS and indicated that disability was significantly correlated with O(2) cost of
      comfortable, fast, and slow over-ground walking. We provide evidence that the
      O(2) cost of walking is an indicator of walking dysfunction in mildly disabled
      persons with MS and should be considered in clinical research and practice.

PMID- 20798969
TI  - Clinical evaluation of Bio-Rad MRSASelectTM medium for the detection of livestock
      associated methicillin-resistant Staphylococcus aureus.
AB  - Bio-Rad MRSASelectTM medium was evaluated for its ability to recover methicillin
      resistant Staphylococcus aureus (MRSA) from nasal samples of pig farmers and
      their household members. In total, 257 samples were inoculated on Bio-Rad
      MRSASelectTM medium with and without broth enrichment and on bioMerieux MRSA ID
      with broth enrichment. A sample was considered to be positive if at least one of
      the media grew MRSA. The sensitivity of Bio-Rad MRSASelectTM medium without broth
      enrichment was 63.9%. With broth enrichment, the sensitivity increased to 98.4%.
      The specificity was 95.4% both with and without broth enrichment. In conclusion,
      Bio-Rad MRSASelectTM medium as well as MRSA ID medium are reliable methods to
      detect MRSA carriage when used in combination with broth enrichment. The directly
      inoculated MRSASelectTM medium was statistically significantly less sensitive
      than the two media after broth enrichment.

PMID- 20798970
TI  - Surveillance programmes for neoplasia in colitis.
AB  - Patients with longstanding extensive colitis, both ulcerative colitis and Crohn's
      colitis, have an increased risk of developing colorectal cancer. Because of this
      risk, colonoscopic surveillance for neoplasia is recommended by most authorities.
      Although there has been no randomised controlled trial to demonstrate
      surveillance effectiveness, there are several retrospective comparative studies,
      which suggest that surveillance reduces colorectal cancer mortality. Over the
      past decade there have been a number of developments in our understanding of
      colitis cancer. We have discovered that the severity of colorectal inflammation
      is an important risk factor, in addition to other known risk factors such as the
      extent and duration of colitis, primary sclerosing cholangitis and a family
      history of colorectal cancer. Endoscopic techniques have also improved and
      evidence now demonstrates that pancolonic chromoendoscopy yields significantly
      more intraepithelial neoplasia than random biopsies. Endoscopic resection of well
      circumscribed lesions is now also recognised as being an appropriate strategy,
      potentially reducing the number of patients requiring colectomy. It is hoped that
      such developments will further improve the effectiveness of colitis surveillance.

PMID- 20798972
TI  - Long-term preserved renal function of a patient with mass-forming granulomatous
      interstitial nephritis by biopsy-based steroid therapy.
AB  - In 2001, a 41-year-old Japanese woman was referred to our hospital because of
      severe renal dysfunction and fever of unknown origin. On admission, her serum
      creatinine was 8.7 mg/dL, urine protein was 0.3 g/day, and urine beta(2)
      microglobulin was 81,007 MUg/day. Computed tomography (CT) scans showed bilateral
      contracted kidneys with a mass projecting from the lower pole of the right
      kidney. Biopsy of this lesion revealed interstitial nephritis and a noncaseating
      granuloma. Because extrarenal organ involvement or laboratory findings specific
      for sarcoidosis or other primary diseases were not detected, idiopathic
      granulomatous interstitial nephritis (GIN) was diagnosed. Prednisolone was
      started at dosage of 30 mg daily, and serum creatinine decreased to 5.5 mg/dL
      after 1 month. Her renal function was preserved for 8 years, but maintenance
      hemodialysis had to be started in 2009. A surgical specimen obtained after
      initiation of dialysis showed resolution of GIN in the renal mass lesion, which
      presumably resulted in preservation of renal function over the long term. Even in
      patients with severe renal dysfunction, histological diagnosis of GIN might lead
      to prognostic improvement because of appropriate therapeutic intervention.

PMID- 20798973
TI  - Tracking delays in report availability caused by incorrect exam status with Web
      based issue tracking: a quality initiative.
AB  - Many radiology information systems (RIS) cannot accept a final report from a
      dictation reporting system before the exam has been completed in the RIS by a
      technologist. A radiologist can still render a report in a reporting system once
      images are available, but the RIS and ancillary systems may not get the results
      because of the study's uncompleted status. This delay in completing the study
      caused an alarming number of delayed reports and was undetected by conventional
      RIS reporting techniques. We developed a Web-based reporting tool to monitor
      uncompleted exams and automatically page section supervisors when a report was
      being delayed by its incomplete status in the RIS. Institutional Review Board
      exemption was obtained. At four imaging centers, a Python script was developed to
      poll the dictation system every 10 min for exams in five different modalities
      that were signed by the radiologist but could not be sent to the RIS. This script
      logged the exams into an existing Web-based tracking tool using PHP and a MySQL
      database. The script also text-paged the modality supervisor. The script logged
      the time at which the report was finally sent, and statistics were aggregated
      onto a separate Web-based reporting tool. Over a 1-year period, the average
      number of uncompleted exams per month and time to problem resolution decreased at
      every imaging center and in almost every imaging modality. Automated feedback
      provides a vital link in improving technologist performance and patient care
      without assigning a human resource to manage report queues.

PMID- 20798971
TI  - Primary biliary cirrhosis and autoimmune hepatitis: apotopes and epitopes.
AB  - Autoimmune liver diseases (ALDs) represent a wide spectrum of chronic
      inflammatory diseases that are characterized by an immune-mediated attack against
      either hepatocytes (in the case of autoimmune hepatitis types 1 and 2, AIH-1, 2)
      or cholangiocytes (in primary biliary cirrhosis, PBC). PBC is considered a model
      autoimmune disease due to the homogeneity of patients, the high specificity of
      antimitochondrial antibodies (AMAs), and the specificity of biliary epithelial
      cell (BEC) destruction. It ensues from a multi-lineage loss of tolerance to the
      E2 component of the pyruvate dehydrogenase complex (PDC-E2). One of the major
      unanswered questions in the pathogenesis of PBC is the specificity of small
      intrahepatic bile duct attack while PDC-E2 is present in mitochondria of
      nucleated cells. Recent findings suggest that the apoptosis of BECs may be of
      considerable importance for understanding PBC, and that they are more than simply
      an innocent victim of an immune attack. Rather, they attract immune attack by
      virtue of the unique biochemical mechanisms by which they handle PDC-E2. The role
      of apoptotic cells in AIH is not well defined, but advances in the study of
      autoreactive T cells stem mostly from AIH type 2, where the main autoantigen
      (CYP2D6) is known, enabling the characterization of antigen-specific immune
      responses. This review article is intended to provide a critical overview of
      current evidence on tissue specificity in ALDs, as well as the characteristics of
      the relevant epitopes and apotopes and their biological and clinical
      significance.

PMID- 20798974
TI  - Polybacterial challenge effects on cytokine/chemokine production by macrophages
      and dendritic cells.
AB  - OBJECTIVE: To investigate the polymicrobial infection of periodontal disease,
      which elicits inflammatory mediators/cytokines/chemokines in the local gingival
      tissues, and a polybacterial challenge of antigen-presenting cells, e.g.
      macrophages and dendritic cells (DCs), at the mucosal surface. MATERIALS AND
      METHODS: The cytokine/chemokine profiles of human macrophages and DCs in response
      to polybacterial challenges were investigated. RESULTS: Oral Gram-negative
      bacteria elicited significantly greater IL-8 levels from macrophages, compared to
      Gram-positive bacteria. Gram-positive bacteria did not show synergism in inducing
      this chemokine from macrophages. In contrast, pairs of oral Gram-negative
      bacteria elicited synergistic production of IL-8 by macrophages. Similar results
      were not observed with TNFalpha, which only appeared additive with the
      polybacterial challenge. Selected Gram-negative bacterial pairs synergized in IL
      6 production by immature DCs. In mature DCs (mDCs), a Porphyromonas
      gingivalis/Fusobacterium nucleatum and Porphyromonas intermedia/F. nucleatum
      polybacterial challenge resulted in significant synergism for IL-6 and TNFalpha
      levels. However, only the Pi/Fn combination synergized for IL-12 production and
      there appeared to be no polybacterial effect on IL-10 production by the mDCs.
      CONCLUSIONS: These results indicate that a polybacterial challenge of cells
      linking innate and adaptive immune responses results in varied response profiles
      that are dependent upon the characteristics of the microorganisms that are
      components of the polybacterial complex.

PMID- 20798975
TI  - Feasibility of oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX-4) in cirrhotic
      or liver transplant patients: experience in a cohort of advanced hepatocellular
      carcinoma patients.
AB  - PURPOSE: The only drug that improves survival in hepatocellular carcinoma is
      sorafenib. FOLFOX-4 regimen is safe and widely used in patients with colorectal
      cancer, yielding interesting results with little toxicity. We conducted a
      retrospective study to evaluate the safety and the effectiveness of FOLFOX-4 in
      cirrhotic or liver transplanted patients with hepatocellular carcinoma ineligible
      for sorafenib. METHODS: Thirty seven patients were enrolled in the study. The
      medical record of either cirrhotic patients or liver transplanted patients with
      advanced hepatocellular carcinoma receiving FOLFOX-4 regimen between November
      1999 and March 2006 were retrospectively analyzed. Patients received oxaliplatin
      85 mg/m(2) as a 2-hour infusion on day one, and leucovorin 200 mg/m(2) as a 2
      hour infusion followed by bolus 5-fluorouracil 400 mg/m(2) and a 48-hours
      infusion of 5-fluorouracil 2400 mg/m(2). Treatment was repeated every 2 weeks
      until disease progression or unacceptable adverse effects occurred. RESULTS:
      Patients had a Child-Pugh class A (n = 16), class B cirrhosis (n = 10) or a liver
      transplant (n = 11) and received 2 to 37 cycles of chemotherapy (total of 310
      cycles). Two (5.4%) cirrhotic patients developed neutropenic sepsis and one
      (2.7%) toxic death occurred. At first assessment, five patients from Child-Pugh
      class A (33%) and two from Child-Pugh class B group (20%) achieved a radiological
      response and/or alpha foeto-protein decrease, and no patient achieved a complete
      response. CONCLUSIONS: In conclusion, with a manageable toxicity profile in
      cirrhotic Child-Pugh class A-B or liver transplanted patients, the FOLFOX-4
      regimen appears to be a feasible treatment option for patients with advanced
      hepatocellular carcinoma unfit for sorafenib. These data need to be confirmed in
      a prospective study.

PMID- 20798976
TI  - Surgical navigation for meningioma surgery.
AB  - The use of surgical navigation systems (SNSs) is well established in intracranial
      surgery for gliomas and metastases yet some doubt its benefit in surgery for
      intracranial meningiomas. In this chapter we review the authors' experiences and
      literature on how use of surgical navigation may be useful in craniotomy for
      intracranial mengingiomas. With the exception of small convexity meningiomas,
      finding the tumor is not a common problem. The most important issues where the
      capabilities of SNS can be used to the surgeon's advantage are optimizing the
      bone and dural opening, avoiding arterial and venous structures, defining the
      frontal air sinuses and determining one's location within a large tumor devoid of
      landmarks. Contemporary SNS can provide instantaneous localization and
      orientation information, as well as utilize multimodality imaging that is
      required to address these problems and is an effective means of optimizing
      surgery for many intracranial meningiomas.

PMID- 20798977
TI  - Volumetric analysis of functional diffusion maps is a predictive imaging
      biomarker for cytotoxic and anti-angiogenic treatments in malignant gliomas.
AB  - Anti-angiogenic agents targeting brain tumor neovasculature may increase
      progression-free survival in patients with recurrent malignant gliomas. However,
      when these patients do recur it is not always apparent as an increase in
      enhancing tumor volume on MRI, which has been the standard of practice for
      following patients with brain tumors. Therefore alternative methods are needed to
      evaluate patients treated with these novel therapies. Furthermore, a method that
      can also provide useful information for the evaluation of conventional therapies
      would provide an important advantage for general applicability. Diffusion
      weighted magnetic resonance imaging (DWI) has the potential to serve as a
      valuable biomarker for these purposes. In the current study, we explore the
      prognostic ability of functional diffusion maps (fDMs), which examine voxel-wise
      changes in the apparent diffusion coefficient (ADC) over time, applied to regions
      of fluid-attenuated inversion recovery (FLAIR) abnormalities in patients with
      malignant glioma, treated with either anti-angiogenic or cytotoxic therapies.
      Results indicate that the rate of change in fDMs is an early predictor of tumor
      progression, time to progression and overall survival for both treatments,
      suggesting the application of fDMs in FLAIR abnormal regions may be a significant
      advance in brain tumor biomarker technology.

PMID- 20798978
TI  - Control of somatic embryogenesis and embryo development by AP2 transcription
      factors.
AB  - Members of the AP2 family of transcription factors, such as BABY BOOM (BBM), play
      important roles in cell proliferation and embryogenesis in Arabidopsis thaliana
      (AtBBM) and Brassica napus (BnBBM) but how this occurs is not understood. We have
      isolated three AP2 genes (GmBBM1, GmAIL5, GmPLT2) from somatic embryo cultures of
      soybean, Glycine max (L.) Merr, and discovered GmBBM1 to be homologous to AtBBM
      and BnBBM. GmAIL5 and GmPLT2 were homologous to Arabidopsis AINTEGUMENTA-like5
      (AIL5) and PLETHORA2 (PLT2), respectively. Constitutive expression of GmBBM1 in
      Arabidopsis induced somatic embryos on vegetative organs and other pleiotropic
      effects on post-germinative vegetative organ development. Sequence comparisons of
      BBM orthologues revealed the presence of ten sequence motifs outside of the AP2
      DNA-binding domains. One of the motifs, bbm-1, was specific to the BBM-like
      genes. Deletion and domain swap analyses revealed that bbm-1 was important for
      somatic embryogenesis and acted cooperatively with at least one other motif,
      euANT2, in the regulation of somatic embryogenesis and embryo development in
      transgenic Arabidopsis. The results provide new insights into the mechanisms by
      which BBM governs embryogenesis.

PMID- 20798979
TI  - Phytochemicals: cancer chemoprevention and suppression of tumor onset and
      metastasis.
AB  - Carcinogenesis is a multi-step process which could be prevented by
      phytochemicals. Phytochemicals from dietary plants and other plant sources such
      as herbs are becoming increasingly important sources of anticancer drugs or
      compounds for cancer chemoprevention or adjuvant chemotherapy. Phytochemicals can
      prevent cancer initiation, promotion, and progression by exerting anti
      inflammatory and anti-oxidative stress effects which are mediated by integrated
      Nrf2, NF-kappaB, and AP-1 signaling pathways. In addition, phytochemicals from
      herbal medicinal plants and/or some dietary plants developed in recent years have
      been shown to induce apoptosis in cancer cells and inhibition of tumor growth in
      vivo. In advanced tumors, a series of changes involving critical signaling
      molecules that would drive tumor cells undergoing epithelial-mesenchymal
      transition and becoming invasive. In this review, we will discuss the potential
      molecular targets and signaling pathways that mediate tumor onset and metastasis.
      In addition, we will shed light on some of the phytochemicals that are capable of
      targeting these signaling pathways which would make them potentially applicable
      to cancer chemoprevention, treatment and control of cancer progression.

PMID- 20798980
TI  - Excitation-wavelength dependent fluorescence of ethyl 5-(4-aminophenyl)-3-amino
      2,4-dicyanobenzoate.
AB  - The excitation wavelength dependence of the steady-state and time-resolved
      emission spectra of ethyl 5-(4-aminophenyl)-3-amino-2,4-dicyanobenzoate (EAADCy)
      in tetrahydrofuran (THF) at room temperature has been examined. It is found that
      the ratio of the fluorescence intensity of the long-wavelength and short
      wavelength fluorescence bands strongly depends on the excitation wavelength,
      whereas the wavelengths of the fluorescence excitation and fluorescence bands
      maxima are independent on the observation/excitation wavelengths. The dynamic
      Stokes shift of fluorophore in locally excited (LE) and intramolecular charge
      transfer (ICT) states has been studied with a time resolution about 30 ps. The
      difference between Stokes shift in the LE and ICT states was attributed to the
      solvent response to the large photoinduced dipole moment of EAADCy in the
      fluorescent charge transfer state. On this base we can state that, the relaxation
      of the polar solvent molecules around the fluorophore was observed.

PMID- 20798981
TI  - Preparation of immunoglobulin Y (IgY) against lipopolysaccharide using gel
      chromatography from the yolks of eggs laid by immunized hens.
AB  - The objective is to prevent and treat injuries caused by lipopolysaccharide (LPS)
      from gram negative bacteria in animals and humans, we produced antibodies against
      LPS from egg yolk. LPS from E. coli (O111:B4) mixed with Freund's Adjuvant was
      used as the immunogen to immunize Roman hens. Immunized eggs were collected, and
      immunoglobulin Y (IgY) was purified using a water solution, salt precipitation
      and gel chromatography. The molecular weight and purity were determined by SDS
      PAGE, the antibody titer by noncompetitive enzyme-linked immunosorbent assay
      (ELISA) and antibody activity against LPS by the mortality of mice
      intraperitoneally injected with LPS or LPS-IgY solutions. IgY against LPS showed
      two protein bands at 68 and 26 kDa on the gel; the antibody titer was almost
      1:25,600. After incubation with LPS, IgY decreased the mortality of mice
      challenged with LPS. This study provided an efficient way to produce high-titer
      egg yolk antibodies, which could attenuate lethal effects of LPS, by immunizing
      hens. Furthermore, the LPS antibody was purified well using a water solution,
      salting-out and gel chromatography.

PMID- 20798982
TI  - Awareness, perceptions, and provider recommendation related to genetic testing
      for hereditary breast cancer risk among at-risk Hispanic women: similarities and
      variations by sub-ethnicity.
AB  - This study explored awareness of risk factors for hereditary breast and ovarian
      cancer (HBOC), awareness, knowledge and concerns about genetic testing, and
      preference for how to have genetic testing recommended by a care provider among
      at-risk Hispanic women. Differences in these factors among Mexican, Cuban, and
      Puerto Rican women were also examined. Women with a personal or family history of
      breast or ovarian cancer from the Tampa Bay Area participated in a qualitative
      interview (N = 53). Data were analyzed using a combination of open and axial
      coding with a grounded theory approach. Study participants in all groups
      reported: being aware that family history was a breast cancer risk factor,
      limited knowledge of genetic testing, fear of test results, concerns about
      children's risks, and no physician referral for genetic testing. Noteworthy sub
      ethnic differences included preferences for physician recommendation and
      information about genetic testing. This study provides important preliminary
      information about areas related to HBOC that require additional education in the
      Hispanic community as a whole and by sub-ethnicity.

PMID- 20798983
TI  - Both malvaceous and non-malvaceous betasatellites are associated with two wild
      cotton species grown under field conditions in Pakistan.
AB  - Betasatellites are symptom-modulating DNA satellites that are associated with the
      majority of monopartite begomoviruses in the Old World. Betasatellites show both
      geographical and host-specific relatedness; those isolated from malvaceous hosts
      form one group and those isolated from non-malvaceous hosts form the second
      group. Real-time PCR based estimation of begomovirus DNA in cotton species grown
      in a living herbarium under field conditions at the Central Cotton Research
      Institute (CCRI), Multan was carried out to understand their role in the ongoing
      cotton leaf curl disease (CLCuD) epidemic in Pakistan. The levels of begomovirus
      DNA in cotton species from the herbarium was found to be several folds lower than
      symptomatic plants of commercially grown cotton. Among herbarium species
      Gossypium anomalum, G. robinsoni and G. somalense contained higher levels of
      begomovirus DNA in comparison to other wild species. Characterization of
      betasatellites from two cotton species (G. anomalum and G. somalense) was carried
      out to understand their role in accumulation of begomovirus DNA. Here, we show
      that the two wild species of cotton are associated with Cotton leaf Multan
      betasatellite (CLCuMB), a malvaceous betasatellite associated with CLCuD, as well
      as Chili leaf curl betasatellite, a non-malvaceous betasatellite not previously
      identified in a malvaceous host. This is the first evidence of the presence of a
      non-malvaceous betasatellite in malvaceous hosts.

PMID- 20798984
TI  - A cohort of balanced reciprocal translocations associated with dyslexia:
      identification of two putative candidate genes at DYX1.
AB  - Dyslexia is one of the most common neurodevelopmental disorders where likely many
      genes are involved in the pathogenesis. So far six candidate dyslexia genes have
      been proposed, and two of these were identified by rare chromosomal
      translocations in affected individuals. By systematic re-examination of all
      translocation carriers in Denmark, we have identified 16 different translocations
      associated with dyslexia. In four families, where the translocation co-segregated
      with the phenotype, one of the breakpoints concurred (at the cytogenetic level)
      with either a known dyslexia linkage region--at 15q21 (DYX1), 2p13 (DYX3) and
      1p36 (DYX8)--or an unpublished linkage region at 19q13. As a first exploitation
      of this unique cohort, we identify three novel candidate dyslexia genes, ZNF280D
      and TCF12 at 15q21, and PDE7B at 6q23.3, by molecular mapping of the familial
      translocation with the 15q21 breakpoint.

PMID- 20798985
TI  - Mitochondrial DNA-based genetic structure analysis of Pudong White pigs.
AB  - There are extensive debates concerning the origin and the necessity of
      conservation of Pudong White pigs in the Taihu region of China. To elucidate
      their genetic ancestry, we sequenced the complete mtDNA D-loop sequences of 25
      Pudong White pigs and 9 Shawutou pigs from the Taihu region and reanalyzed 158
      published sequences of other breeds in GenBank. Haplotypes of all pigs were
      classified into two clades, A and E, but Pudong White pigs were found only in
      clade A. The results of population differentiation demonstrated that there were
      few genetic exchanges among the eight populations. Furthermore, divergence time
      estimates suggested that the Pudong White pigs split from four types of Taihu
      pigs at about 0.26-0.75 million years ago. Overall, the results suggest that the
      Pudong White pig is a unique population, and conservation practice should
      concentrate on preserving this isolated population.

PMID- 20798986
TI  - The CYP17A1 -34T > C polymorphism and breast cancer risk in BRCA1 and BRCA2
      mutation carriers.
AB  - Exposure to estrogen has a major effect on breast cancer risk. A polymorphism (
      34 T > C; rs743572) in the cytochrome P450c17alpha gene (CYP17A1) encoding an
      enzyme which controls estrogen levels was reportedly associated with breast
      cancer risk in average risk populations. The effect of this polymorphism on
      breast or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers has not been
      thoroughly investigated. With this aim, 2,221 BRCA1 and BRCA2 mutation carriers
      (1,313 with breast cancer, 279 with ovarian cancer, and 695 asymptomatic
      carriers), with either BRCA1 (n = 1693) or BRCA2 (n = 528) germline mutations
      from seven centers were genotyped for the -34 T > C CYP17 polymorphism.
      Genotyping was accomplished using Taqman allelic discrimination, matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) or
      PCR-based restriction-fragment length polymorphism analysis, and limited
      sequencing. Data were analyzed using Cox proportional hazards models. The hazard
      ratios (HRs) for breast cancer was 1.02 (95% CI 0.89-1.17, p = 0.74) and 1.10
      (95% CI 0.72-1.67, p = 0.66) for BRCA1 and BRCA2 mutation carriers, respectively.
      The HRs for ovarian cancer were 1.17 (0.94-1.46, p = 0.17) and 0.91 (0.31-2.67, p
      = 0.86) for BRCA1 and BRCA2 mutation carriers, respectively. Results remained
      unaltered when the Israeli cohort (primarily Ashkenazim) was evaluated
      separately. In conclusion, there was no overall evidence for an association of
      the -34 T > C CYP17 polymorphism with either breast or ovarian cancer risk in
      BRCA1 or BRCA2 mutation carriers.

PMID- 20798987
TI  - Dau c 1.01 and Dau c 1.02-silenced transgenic carrot plants show reduced
      allergenicity to patients with carrot allergy.
AB  - Pathogenesis-related protein-10 (PR10) is a ubiquitous small plant protein
      induced by microbial pathogens and abiotic stress that adversely contributes to
      the allergenic potency of many fruits and vegetables, including carrot. In this
      plant, two highly similar genes encoding PR10 isoforms have been isolated and
      designated as allergen Dau c 1.01 and Dau c 1.02. The aim of the study was to
      generate PR10-reduced hypoallergenic carrots by silencing either one of these
      genes in transgenic carrots by means of RNA interference (RNAi). The efficiency
      of gene silencing by stably expressed hairpin RNA (hnRNA) was documented by means
      of quantitative RT-PCR (qPCR) and immunoblotting. Quantification of the residual
      protein revealed that PR10 accumulation was strongly decreased compared with
      untransformed controls. Treatment of carrot plants with the PR protein-inducing
      chemical salicylic acid resulted in an increase of PR10 isoforms only in wild
      type but not in Dau c 1-silenced mutants. The decrease of the allergenic
      potential in Dau c 1-silenced plants was sufficient to cause a reduced allergenic
      reactivity in patients with carrot allergy, as determined with skin prick tests
      (SPT). However, simultaneous silencing of multiple allergens will be required to
      design hypoallergenic carrots for the market. Our findings demonstrate the
      feasibility of creating low-allergenic food by using RNAi. This constitutes a
      reasonable approach to allergen avoidance.

PMID- 20798988
TI  - Clinical pharmacist counseling improves outcomes for Taiwanese asthma patients.
AB  - OBJECTIVE: To assess the impact of an asthma educational program provided by a
      nurse combined with asthma counseling provided by a pharmacist on asthma
      knowledge, quality of life and clinical outcomes in Taiwanese patients with
      asthma. SETTING: All patients were recruited from Pulmonary Medicine outpatient
      clinic, the Tri-Service General Hospital, Taipei, Taiwan. Asthma education was
      given in three one-hour sessions offered during monthly clinic visits. METHOD: A
      total of 91 asthma patients were randomly assigned to a nurse-administered
      education program (Group 1), the education program with additional pharmacist
      counseling (Group 2), or a control group receiving routine care only (control).
      Three questionnaires were used for assessment at months 0, 3 and 6. Outcomes were
      compared between groups to determine efficacy. MAIN OUTCOME MEASURE: Asthma
      knowledge, health-related quality of life, and medication adherence were measured
      at baseline and 3 and 6 months after enrollment. RESULTS: A total of 104 patients
      were enrolled; 91 completed the study. Knowledge scores of patients in Groups 1
      and 2 increased significantly compared to control group. Both intervention groups
      showed significant increases in knowledge scores with longer follow-up. Group 2
      showed a significant improvement in clinical symptoms between baseline (month 0)
      and month 6 (4.99 vs. 4.21, P=0.008). No significant differences in medication
      adherence were seen among groups. CONCLUSION: Regular nurse-administered asthma
      education with additional pharmacist counseling improves asthma knowledge and
      clinical symptoms in asthma patients.

PMID- 20798989
TI  - Assessment of global function of left ventricle with dual-source CT in patients
      with severe arrhythmia: a comparison with the use of two-dimensional
      transthoracic echocardiography.
AB  - To evaluate the agreement between dual-source computed tomography (DSCT) and two
      dimensional transthoracic echocardiography (2D-TTE) with respect to the
      assessment of global left ventricular (LV) function in patients with severe
      arrhythmia. With 2D-TTE serving as the reference method, we performed both DSCT
      and 2D-TTE, at an interval of less than 2 days, in 54 patients with severe
      arrhythmia (average heart rate difference >30 beats per min) before open heart
      surgery for evaluation of valvular heart disease (VHD) and coronary artery
      disease. DSCT was performed using retrospective electrocardiography (ECG) without
      dose modulation. Ten phases of the cardiac cycle were analyzed for identification
      of end-diastolic and end-systolic phases with ECG-editing. Pearson's correlation
      coefficient (r) and Bland-Altman analysis were used to determine agreement for
      parameters of LV global function. Correlation between DSCT and 2D-TTE
      measurements was good or excellent in terms of the values of the LV ejection
      fraction (51.0 +/- 11.4% vs. 55.8 +/- 11.6%; r = 0.8), LV end-diastolic volume
      (179.5 +/- 98.6 ml vs. 152.1 +/- 73.8 ml; r = 0.95), LV end-systolic volume (90.7
      +/- 60.7 ml vs. 69.1 +/- 46.8 ml; r = 0.90), and LV stroke volume (89.0 +/- 48.1
      ml vs. 82.9 +/- 37.3 ml; r = 0.89). Left ventricular ejection fraction measured
      using DSCT was less than that measured using 2D-TTE by an average of -4.8 +/-
      7.3%. Dual-source CT with ECG editing can provide results comparable to those of
      2D-TTE for assessment of LV global function in patients with severe arrhythmia.

PMID- 20798990
TI  - Prevalence of hematological abnormalities in patients with Sheehan's syndrome:
      response to replacement of glucocorticoids and thyroxine.
AB  - Anemia and other hematological abnormalities are common in patients with
      Sheehan's syndrome. The response of these abnormalities to replacement of
      thyroxine and glucocorticoids is not clear. The aim of the present study was to
      document the profile of hematological abnormalities and response to treatment in
      patients with Sheehan's syndrome. Forty patients of Sheehan's syndrome and an
      equal number of age and parity matched healthy controls were studied for
      prevalence of hematological abnormalities. Hemoglobin concentration, hematocrit,
      red cell, white cell and platelet count were significantly decreased in patients
      with Sheehan's syndrome compared to controls. Frequency of anemia, leucopenia,
      thrombocytopenia and pancytopenia was significantly higher in these patients
      compared to controls. After achieving euthyroid and eucortisol state, there was a
      complete recovery of these hematological abnormalities. We conclude that anemia
      and other cytopenias are common in patients with Sheehan's syndrome and
      replacement with thyroxine and glucocorticoids results in complete recovery of
      these abnormalities.

PMID- 20798991
TI  - [Health - History and conceptions of the guiding notion of medicine].
AB  - In the history of medicine the notion of health was conceptualized in many
      different ways. From the perspective of a history of ideas, however, all
      approaches appear to be based on a limited number of ten basic conceptions.
      Health can be seen under the paradigm of harmony, struggle, dialectics,
      hierarchy, potentiality, transcendence, autonomy, causality, organization, and
      plurality. Since the paradigm of scientific causality, prevailing in modern
      medicine, seems not to cover all aspects of patients' live-world health
      experience, the challenge for doctors remains to also consider other - seemingly
      outdated - concepts of health, depending on the patient and his or her cultural
      background.

PMID- 20798992
TI  - Summer climate and mortality in Vienna - a human-biometeorological approach of
      heat-related mortality during the heat waves in 2003.
AB  - BACKGROUND: Strong heat load has negative impacts on the human health and results
      in higher mortality during heat waves. In Europe, the summer 2003 was responsible
      for a high number of heat-related deaths, especially in Western Europe. Vienna
      was only partially affected. The aim of this study is to compare the heat-related
      mortality of 2003 with other years and to analyze whether 2003 was exceptional in
      Vienna. METHODS: The analysis is based on both meteorological and mortality data
      for the federal state of Vienna (Austria) for 1970-2007. We used the human
      biometeorological index Physiologically Equivalent Temperature (PET) in order to
      assess the heat load affecting the human body, and considered short-term
      adaptation by the HeRATE approach. Each day between April and October was
      classified according to its thermal stress level and the mean mortality for each
      class was analyzed. Two approaches, with and without long-term sensitivity trends
      were considered. RESULTS: Mortality increases significantly with thermal stress,
      but this increase attenuated in the last decades. Based on the sensitivity for
      the period of investigation, 2003 was the year with the highest heat-related
      mortality. Including the long-term sensitivity trend, other years (1992, 1994 and
      2000) were characterised by higher values. DISCUSSION: In the last decades the
      number of days with heat stress increased, but the sensitivity to heat stress
      decreased. This could indicate long-term adaptation processes. Hence, heat
      related mortality in 2003 was high, but not exceptionally high.

PMID- 20798993
TI  - Assessment of heavy metals in the particulate matter of two Brazilian
      metropolitan areas by using Tillandsia usneoides as atmospheric biomonitor.
AB  - PURPOSE: The aims of this paper were to quantify the heavy metals (HM) in the air
      of different sites in Rio de Janeiro (RJ) and Salvador (SA) using Tillandsia
      usneoides (Bromeliaceae) as a biomonitor, and to study the morphology and
      elemental composition of the air particulate matter (PM) retained on the
      Tillandsia surface. METHODS: Tillandsia samples were collected in a
      noncontaminated area and exposed to the air of five sites in RJ State and seven
      in SA for 45 days, in two seasons. Samples were prepared to HM quantification by
      flame atomic absorption spectrophotometry, while morphological and elemental
      characterizations were studied by using scanning electron microscopy. RESULTS: HM
      concentrations were significantly higher when compared to control sites. We found
      an increasing metal concentration as follows: Cd < Cr < Pb < Cu < Zn. PM
      exhibited a morphology varying from amorphous- to polygonal-shaped particles.
      Size measurements indicated that more than 80% of particles were less than 10
      MUm. PM contained aluminosilicates iron-rich particles, but Zn, Cu, Cr, and Ba
      were also detected. CONCLUSION: HM input in the atmosphere was mainly associated
      with anthropogenic sources such as vehicle exhaust. Elemental analysis detected
      HM in the inhalable particles, indicating that those HMs may intensify the toxic
      effects of PM on human health. Our results indicated T. usneoides as an adequate
      biomonitor of HM in the PM belonging to the inhalable fraction.

PMID- 20798994
TI  - How does cellular contact affect differentiation mediated pattern formation?
AB  - In this paper, we present a two-population continuous integro-differential model
      of cell differentiation, using a non-local term to describe the influence of the
      local environment on differentiation. We investigate three different versions of
      the model, with differentiation being cell autonomous, regulated via a community
      effect, or weakly dependent on the local cellular environment. We consider the
      spatial patterns that such different modes of differentiation produce, and
      investigate the formation of both stripes and spots by the model. We show that
      pattern formation only occurs when differentiation is regulated by a strong
      community effect. In this case, permanent spatial patterns only occur under a
      precise relationship between the parameters characterising cell dynamics,
      although transient patterns can persist for biologically relevant timescales when
      this condition is relaxed. In all cases, the long-lived patterns consist only of
      stripes, not spots.

PMID- 20798995
TI  - Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S). One to
      three-year follow-up.
AB  - Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a new
      operation for morbid obesity based on the biliopancreatic diversion in which a
      sleeve gastrectomy is followed by an end-to-side duodeno-ileal diversion. The
      preservation of the pylorus makes possible the reconstruction in one loop, which
      reduces operating time and needs no mesentery opening. We review the results
      obtained on the first 50 operated patients with 1 to 3 years follow-up. Eighteen
      men and 32 women with a mean BMI of 44 kg/m(2) were operated on. Hypertension was
      present in 50%, sleep apnea in 30%, hypertriglyceridemia in 60% and
      hypercholesterolemia in 43%.There were 27 type two diabetics, most of them on
      insulin therapy. There were two gastric staple-line leaks and one long-term
      subphrenic abscess. Follow-up is complete for 98% of the patients. Excess weight
      loss reached 94.7% at 1 year, and it was maintained over the second and third
      year. At 1 year, mild anemia has been detected in 10% of the cases. Albumin
      concentration was under normal levels in 8% of the patients in the first
      postoperative year, but all patients recovered to normal levels by the third
      postoperative year. All diabetic patients have normalized glucose or HbA1c levels
      after the sixth postoperative month with no need of anti-diabetic therapy. SADI-S
      is a promising operation which offers excellent weight loss and metabolic
      results. The elimination of one anastomosis reduces operative time and decreases
      the possibility of surgically related complications.

PMID- 20798996
TI  - Cerium relieves the inhibition of chlorophyll biosynthesis of maize caused by
      magnesium deficiency.
AB  - Lanthanoids (Ln) were demonstrated to improve chlorophyll formation and the
      growth of plants. But the mechanism of the fact that Ln promotes chlorophyll
      biosynthesis of plants is poorly understood. The main aim of the study was to
      determine Ln effects in chlorophyll formation of maize under magnesium (Mg)
      deficiency. Maize plants were cultivated in Hoagland's solution. They were
      subjected to Mg deficiency and to cerium administered in Mg-deficient Hoagland's
      media, and then the contents of various chlorophyll precursors and gen
      expressions of the key enzymes of chlorophyll biosynthesis were examined. The
      decrease of chlorophyll contents in maize leaves caused by Mg deficiency
      suggested an inhibition of chlorophyll synthesis that was inhibited by a
      reduction of the precursors as measured by analyzing the contents of delta
      aminolevulinic acid, porphobilinogen, uroporphyrinogen III, Mg-protoporphyrin IX,
      and protochlorophyll, as well as the expression levels of magnesium chelatase,
      magnesium-protoporphyrin IX methyltransferase, and chlorophyll synthase; Mg
      deficiency significantly inhibited the transformation from coproporphyrinogen III
      or protoporphyrin IX to chlorophyll. However, cerium addition significantly
      relieved the inhibition of chlorophyll biosynthesis in maize caused by Mg
      deficiency and increased chlorophyll content and promoted a series of
      transformations from delta-aminolevulinic acid to chlorophyll and maize growth
      under Mg deficiency. It implied that cerium might partly substitute for the role
      of Mg.

PMID- 20798997
TI  - Effects of different medical treatments on serum copper, selenium and zinc levels
      in patients with rheumatoid arthritis.
AB  - The aim of the present study was to measure the changes in serum selenium, zinc,
      and copper in patients being treated for rheumatoid arthritis. Thirty-two
      patients and 52 healthy controls were included in the study. The copper level was
      higher and those of selenium and zinc were lower in the patients relative to
      controls. Treatment with methotrexate elevated the zinc levels, but not zinc and
      selenium. Treatments with salazopyrin, corticosteroids, chloroquine, and non
      steroidal anti-inflammatory drugs did not change the levels of any of the
      elements studied. The decrease in zinc and selenium levels and elevation in
      copper levels observed in the patients probably resulted from the defense
      response of organism and are mediated by inflammatory-like substances.

PMID- 20798998
TI  - Oral iron treatment has a positive effect on iron metabolism in elite soccer
      players.
AB  - The purpose of this study was to assess the effects of oral iron supplementation
      on hematological and iron metabolism in elite soccer players. Thirty-five members
      of the Real Zaragoza SAD soccer team took part in this study: group A (GA, n =
      24; Spanish Premier League) took an oral iron supplement of 80 mg day(-1) for 3
      weeks, and group B (GB, n = 11; Spanish Third Division League) did not receive
      any supplementation. In GA, the parameters were measured before and after giving
      the iron supplements, while in GB, measurements were only made at the time of
      collecting the second set of data from GA. After supplementation, GA showed an
      increase in serum iron (SI) (P < 0.05), serum ferritin (Ftn) (P < 0.01), and
      transferrin saturation (Sat) (P < 0.01) with respect to the basal values. In
      addition, GA showed higher values of hematocrit (P < 0.01), mean corpuscular
      volume (P < 0.01), Ftn (P < 0.01), and Sat (P < 0.01) than GB. No significant
      differences were found in any other parameters. More specifically, a higher
      percentage of players had Ftn levels above upper limits in GA vs. GB (P < 0.05),
      and GB had a higher incidence of Ftn below lower limits with respect to subjects
      in GA (P < 0.01). Further, after treatment, 58.3% of GA had >800 mg of SI, while
      all players in GB presented levels below the lower limits. In conclusion, iron
      supplementation with 80 mg.day(-1) for 3 weeks, before the start of the soccer
      season, can be recommended for elite soccer players.

PMID- 20798999
TI  - Emerging modelling methodologies in medicine and biology, Introduction to the
      special issue.

PMID- 20799000
TI  - Neurofibromatosis type 1-associated wild-type gastrointestinal stromal tumor
      treated with anti-IGF-1R monoclonal antibody.
AB  - Gastrointestinal stromal tumors lacking mutations in KIT or PDGFRalpha are known
      as wild type (WT) and are less responsive to imatinib. These WT tumors are
      hypothesized to be dependent on signaling through the insulin-like growth factor
      1 receptor (IGF-1R). We report the case of a 29-year-old woman with
      neurofibromatosis type 1-associated WT GIST treated with an anti-IGF-1R
      monoclonal antibody. Treatment was ineffective, and the potential basis for lack
      of response is discussed in the context of IGF-1R expression levels measured
      within this patients' primary tumor. We suggest that future clinical trials of
      anti-IGF-1R therapies prospectively determine tumor IGF-1R expression levels for
      correlation with response to treatment.

PMID- 20799001
TI  - New advances in noninvasive imaging of the carotid artery: CIMT, contrast
      enhanced ultrasound, and vasa vasorum.
AB  - Carotid ultrasound measurement of carotid intima-media thickness (CIMT) and
      detection of plaques is a useful method to better assess cardiovascular disease
      risk status, especially in those at intermediate risk. We discuss the use CIMT
      and other emerging techniques such as contrast-enhanced carotid ultrasound
      imaging in the evaluation of the carotid artery and its value in cardiovascular
      disease.

PMID- 20799002
TI  - Neurogenic stuttering: its reticular modulation.
AB  - Emerging neurologic evidence has suggested that developmental and acquired
      stuttering may have a cerebral base. Investigations have revealed compensatory
      activation in the right cortical motor areas and deactivation in the left
      perisylvian region in subjects with persistent developmental stuttering. The
      evidence has also implicated limbic (cingulate)-basal ganglia regions. Increased
      speech fluency with treatment in such subjects eliminated compensatory brain
      activity and shifted activation back to the left hemisphere. We assess the
      neurology of stuttering and then present our own observations of deep brain
      stimulation of the thalamus with some ameliorating effect on the encompassing
      syndrome with speech dysfluency.

PMID- 20799003
TI  - A meta-analysis of morphological interventions: effects on literacy achievement
      of children with literacy difficulties.
AB  - This study synthesizes 79 standardized mean-change differences between control
      and treatment groups from 17 independent studies, investigating the effect of
      morphological interventions on literacy outcomes for students with literacy
      difficulties. Average total sample size ranged from 15 to 261 from a wide range
      of grade levels. Overall, morphological instruction showed a significant
      improvement on literacy achievement (d = 0.33). Specifically, its effect was
      significant on several literacy outcomes such as phonological awareness (d =
      0.49), morphological awareness (d = 0.40), vocabulary (d = 0.40), reading
      comprehension (d = 0.24), and spelling (d = 0.20). Morphological instruction was
      particularly effective for children with reading, learning, or speech and
      language disabilities, English language learners, and struggling readers,
      suggesting the possibility that morphological instruction can remediate
      phonological processing challenges. Other moderators were also explored to
      explain differences in morphological intervention effects. These findings suggest
      students with literacy difficulties would benefit from morphological instruction.

PMID- 20799004
TI  - Genomic profiles in B cell lymphoma.
AB  - Chromosome translocations found in B cell lymphomas generate typical genome
      profiles that are characteristic of each disease entity. The mechanisms of
      lymphomagenesis have been investigated with respect to the involvement of
      deregulated genes in tumor development, as characterized by the promotion of cell
      proliferation and the blockage of cell differentiation and anti-apoptosis. It is
      now well known that chromosome translocation alone does not induce tumor
      formation. New technology such as array CGH and expression profiling introduced
      as a result of the human genome project introduced a new paradigm from which to
      understand the molecular mechanisms of lymphoma development. Analyses with this
      new technology revealed that genome profiles of disease entities are
      characteristic and differ from disease to disease, although the genome profile of
      each patient with the same disease entity varies significantly given the
      recurrent genetic alterations frequently found. These apparent paradoxical
      findings are likely to be the cause of heterogeneity of the clinicopathological
      features associated with the same disease entity. Based on these findings, the
      future prospect and direction of lymphoma research will be discussed.

PMID- 20799005
TI  - Effects of the PREMIER interventions on health-related quality of life.
AB  - BACKGROUND: Health-related quality of life (HRQOL) is an important aspect of well
      being that may improve with health behavior interventions. However, health
      behavior change is difficult with pressure to maintain status quo. PURPOSE: This
      report examines the effects of two lifestyle interventions and an advice-only
      condition on HRQOL. Effects of meeting behavioral goals and weight loss also were
      examined. METHODS: Participants were 295 men and 467 women (34% African American)
      with pre-hypertension or stage 1 hypertension from the PREMIER trial. HRQOL was
      assessed by the Short Form-36. Participants were assigned randomly to (1) advice
      only (ADVICE), (2) established guidelines for blood pressure control (EST), or
      (3) established guidelines plus the Dietary Approaches to Stop Hypertension
      (DASH) dietary pattern (EST + DASH). RESULTS: Assignment to EST resulted in
      improvement in three HRQOL subscales at 6 months and one at 18 months relative to
      ADVICE. EST + DASH improved in two subscales at 6 and 18 months compared with
      ADVICE. Across conditions, total fat, saturated fat, fruit, and vegetable intake
      change, along with >= 4-kg weight loss, resulted in HRQOL improvements at 6 and
      18 months. No improvement was found for change in physical activity, and only a
      few HRQOL subscales were associated with change in sodium and low-fat dairy
      intake. CONCLUSIONS: Intensive lifestyle interventions can result in improvements
      in HRQOL. Change in dietary intake and weight loss is also important.

PMID- 20799006
TI  - The role of opioid receptor antagonists in the treatment of opioid-induced
      constipation: a review.
AB  - Opioid-induced constipation (OIC) is associated with negative impact of opioid
      analgesics on opioid receptors located in the gut wall. Until recently, OIC was
      treated symptomatically only, with different laxatives which did not target the
      pathophysiology of OIC. Recently, several opioid receptor antagonists have been
      introduced in the treatment of OIC. Methylnaltrexone (MNTX) is a peripheral mu
      opioid receptor antagonist for subcutaneous administration, which does not evoke
      symptoms of opioid abstinence. MNTX is indicated for patients with OIC who are
      not amenable to therapy with oral laxatives. In clinical trials, the
      effectiveness of MNTX assessed as its ability to induce spontaneous bowel
      movement, is 50%-60% of treated patients; MNTX demonstrates significant
      superiority over placebo. Another product is combination of oral formulation of
      prolonged release oxycodone and prolonged release naloxone (PR oxycodone/PR
      naloxone), indicated for patients who require opioid administration for chronic
      pain and have already developed OIC, and for those who need opioid therapy and
      take the drug to prevent OIC. Naloxone administered orally displays local,
      antagonist effects on opioid receptors in the gut wall, negligible systemic
      bioavailability, and significantly reduces the oxycodone constipating effect. PR
      oxycodone/PR naloxone has similar analgesic efficacy, but causes less
      constipation and less laxative consumption in comparison with patients treated
      with oxycodone alone. Both products are expensive, therefore their administration
      should be carefully considered. On the other hand, uncontrolled OIC and the
      necessity to perform rectal invasive procedures (enema, manual evacuation) lead
      not only to increased health care costs, but most importantly, cause severe
      patient suffering.

PMID- 20799007
TI  - Comparative antibiotic failure rates in the treatment of community-acquired
      pneumonia: Results from a claims analysis.
AB  - INTRODUCTION: Antibiotic treatment failure contributes to the economic and
      humanistic burdens of community-acquired pneumonia (CAP) by increasing morbidity,
      mortality, and healthcare costs. This study compared treatment failure rates of
      levofloxacin with those of other antibiotics in a large US sample. METHODS:
      Medical and pharmacy claims in the nationally representative SDI database were
      used to identify adults with a new outpatient diagnosis of CAP receiving a study
      antibiotic (levofloxacin, amoxicillin/clavulanate, azithromycin, moxifloxacin)
      between September 1, 2005 and March 31, 2008. Treatment failure was defined as
      >=1 of the following events <=30 days after index date: a refill for the index
      antibiotic after completed days of therapy, a different antibiotic dispensed >1
      day after the index prescription, or hospitalization with a pneumonia diagnosis
      or emergency department visit >3 days postindex. Cohorts were propensity score
      matched for demographic and clinical characteristics. Treatment failure rates
      were compared between pairs of cohorts for the full sample and for high-risk
      patients (age >=65 and/or on Medicaid). RESULTS: Among the 3994 study patients,
      the numbers of dispensed index prescriptions were 268 for
      amoxicillin/clavulanate, 1609 for azithromycin, 1460 for levofloxacin, and 657
      for moxifloxacin. Unadjusted treatment failure rates for the sample were 20.8%
      for levofloxacin, 23.9% for amoxicillin/clavulanate, 23.9% for azithromycin, and
      19.9% for moxifloxacin. For high-risk patients, unadjusted treatment failure
      rates were 19.1% for levofloxacin, 26.1% for amoxicillin/clavulanate, 26.3% for
      azithromycin, and 24.3% for moxifloxacin. Propensity score-matched treatment
      failure rates were significantly lower with levofloxacin than azithromycin (19.8%
      vs. 24.5%, odds ratio [OR] comparator vs. levofloxacin 1.38; 95% CI: 1.14, 1.67),
      a difference amplified in high-risk patients (19.0% vs. 26.4%, OR 1.61; 95% CI:
      1.22, 2.13). No significant differences were observed for other paired
      comparisons. CONCLUSION: In a large US sample, treatment failure in CAP appeared
      to be less likely with quinolones (such as levofloxacin) than azithromycin, an
      effect particularly marked in high-risk patients (age >=65 and/or on Medicaid).

PMID- 20799008
TI  - Cardiovascular therapeutic discovery.

PMID- 20799009
TI  - The Meckel's cartilage in human embryonic and early fetal periods.
AB  - The Meckel's cartilage itself and the mandible are derived from the first
      branchial arch, and their development depends upon the contribution of the
      cranial neural crest cells. The prenatal development of the Meckel's cartilage,
      along with its relationship to the developing mandible and the related
      structures, were studied histologically in human embryos and fetuses. The
      material was obtained from a collection of the Department of Anatomy, and
      laboratory procedures were used to prepare sections, which were stained according
      to standard light-microscopy methods. The formation of the Meckel's cartilage and
      its related structures was observed and documented. Some critical moments in the
      development of the Meckel's cartilage are suggested. The sequential development
      of the Meckel's cartilage started as early as stage 13 (32 days) with the
      appearance of condensation of mesenchymal cells within the mandibular prominence.
      During stage 17 (41 days), the primary ossification center of the mandible
      appeared on the inferior margin of the Meckel's cartilage. The muscular
      attachments to the Meckel's cartilage in embryos were observed at stage 18 (44
      days). Their subsequent movement into the developing mandible during the 10th
      week seemed to diminish the role of the Meckel's cartilage as the supportive
      core; simultaneously, the process of regression within the cartilage was induced.
      During the embryonic period, the bilateral Meckel's cartilages were in closest
      contact at the posterior surface of their superior margins, preceding formation
      of the symphyseal cartilage at this site. The event sequence in the development
      of the Meckel's cartilage is finally discussed.

PMID- 20799010
TI  - Editorial: Stress metabolism of plants.

PMID- 20799011
TI  - The brain microenvironment and cancer metastasis.
AB  - The process of metastasis consists of a series of sequential, selective steps
      that few cells can complete. The outcome of cancer metastasis depends on multiple
      interactions between metastatic cells and homeostatic mechanisms that are unique
      to one or another organ microenvironment. The specific organ microenvironment
      determines the extent of cancer cell proliferation, angiogenesis, invasion and
      survival. Many lung cancer, breast cancer, and melanoma patients develop fatal
      brain metastases that do not respond to therapy. The blood-brain barrier is
      intact in and around brain metastases that are smaller than 0.25 mm in diameter.
      Although the blood-brain barrier is leaky in larger metastases, the lesions are
      resistant to many chemotherapeutic drugs. Activated astrocytes surround and
      infiltrate brain metastases. The physiological role of astrocytes is to protect
      against neurotoxicity. Our current data demonstrate that activated astrocytes
      also protect tumor cells against chemotherapeutic drugs.

PMID- 20799012
TI  - Tyr1 and Ile7 of glucose-dependent insulinotropic polypeptide (GIP) confer
      differential ligand selectivity toward GIP and glucagon-like peptide-1 receptors.
AB  - Glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide
      (GIP) are incretin hormones released in response to food intake and potentiate
      insulin secretion from pancreatic beta cells through their distinct yet related G
      protein-coupled receptors, GLP1R and GIPR. While GLP-1 and GIP exhibit similarity
      in their N-terminal sequence and overall alpha-helical structure, GLP-1 does not
      bind to GIPR and vice versa. To determine which amino acid residues of these
      peptide ligands are responsible for specific interaction with their respective
      receptors, we generated mutant GIP in which several GLP-1-specific amino acid
      residues were substituted for the original amino acids. The potency of the mutant
      ligands was examined using HEK293 cells transfected with GLP1R or GIPR expression
      plasmids together with a cAMP-responsive element-driven luciferase (CRE-luc)
      reporter plasmid. A mutated GIP peptide in which Tyr(1), Ile(7), Asp(15), and
      His(18) were replaced by His, Thr, Glu, and Ala, respectively, was able to
      activate both GLP1R and GIPR with moderate potency. Replacing the original Tyr(1)
      and/or Ile(7) in the N-terminal moiety of this mutant peptide allowed full
      activation of GIPR but not of GLP1R. However, reintroducing Asp(15) and/or
      His(18) in the central alpha-helical region did not significantly alter the
      ligand potency. These results suggest that Tyr/His(1) and Ile/Thr(7) of GIP/GLP-1
      peptides confer differential ligand selectivity toward GIPR and GLP1R.

PMID- 20799013
TI  - New challenges for the Japanese Journal of Radiology (JJR).

PMID- 20799014
TI  - Tract-specific analysis for investigation of Alzheimer disease: a brief review.
AB  - Magnetic resonance diffusion tensor imaging is a noninvasive technique that can
      identify white matter tracts by evaluating bulk diffusion of water in three
      dimensions and can thus describe the microarchitectural characteristics of local
      brain tissue. Several recent reports have shown that mapping of diffusion
      parameters is potentially useful for speculating about the pathology of Alzheimer
      disease (AD). These reports have employed image-analysis approaches, including
      region-of-interest measurement, voxel-based analysis, tract-based spatial
      statistics, and tract-specific analysis (TSA). The present review focuses on TSA
      to investigate AD. An overview of the changes in diffusion properties of AD
      measured using TSA is presented and discussed.

PMID- 20799015
TI  - Inferior phrenic arteries: angiographic anatomy, variations, and catheterization
      techniques for transcatheter arterial chemoembolization.
AB  - The inferior phrenic artery (IPA) is the most common extrahepatic collateral
      vessel to hepatocellular carcinoma (HCC); however, there are many anatomical
      variations in its origin and branches. In addition, the IPA is frequently
      reconstructed through several pathways, mainly through the retroperitoneal
      network, because of the occlusion of its orifice due to atherosclerosis or
      previous catheter manipulation. Infrequently, selective catheterization into the
      IPA is impossible even using a microcatheter, particularly in the IPA that
      originates from the proximal or distal portion of the celiac trunk or from the
      aorta with an acute angle. In this article, we describe anatomical variations of
      the IPA and catheterization techniques, such as a catheter with a large side hole
      and a catheter with a cleft, to facilitate catheterization into the IPA that is
      difficult using a conventional coaxial technique. Radiologists should have
      sufficient knowledge of such variations and catheterization techniques to perform
      transcatheter arterial chemoembolization for HCCs through the IPA effectively and
      safely.

PMID- 20799016
TI  - Technical success rates and long-term patency of endovascular treatment for
      occluded native hemodialysis fistulas: comparison between thrombotic occlusion
      and nonthrombotic occlusion.
AB  - PURPOSE: This study evaluated the technical success and long-term patency of
      endovascular treatment for occluded native hemodialysis fistulas caused by
      thrombotic occlusion (TO) and nonthrombotic occlusion (NTO). MATERIALS AND
      METHODS: This cohort included 96 consecutive occlusions (70 TOs and 26 NTOs) at
      the forearm. Clinical success and patency rates of endovascular treatment were
      calculated and compared between the TO and NTO groups. RESULTS: Overall clinical
      success rate was 91.6%; and primary, assisted primary, and secondary patency
      rates at 1, 2, and 3 years were 49.6%, 30.7%, and 28.3%, respectively; 73.8%,
      48.3%, and 48.3%, respectively; and 80.7%, 72.3%, and 66.2%, respectively.
      Clinical success rates of the TO and NTO groups were 91.4% and 92.3%,
      respectively. The 1-, 2-, and 3-year primary, assisted primary, and secondary
      patency rates of the TO group were 54.4%, 29.3%, and 25.6%, respectively; 70.7%,
      49.4%, and 49.4%, respectively, and 78%, 68.8%, and 64,2%, respectively. Those of
      the NTO group were 38.9%, 32.4%, and 32.4%, respectively; 81.2%, 47.3%, and
      40.6%, respectively; and 87%, 80.3%, and 70.2%, respectively. There were no
      significant differences between the clinical success and patency rates of the two
      groups. CONCLUSION: Occluded native hemodialysis fistulas were restored with high
      frequency, without significant differences between clinical success and patency
      in the TO and NTO groups.

PMID- 20799017
TI  - Percutaneous transluminal venoplasty after venous pressure measurement in
      patients with hepatic venous outflow obstruction after living donor liver
      transplantation.
AB  - PURPOSE: The aim of this study was to evaluate retrospectively the outcome of
      percutaneous transluminal venoplasty (PTV) after venous pressure measurement in
      patients with hepatic venous outflow obstruction following living donor liver
      transplantation (LDLT). MATERIALS AND METHODS: We studied 24 consecutive patients
      suspected of having hepatic venous outflow obstruction after LDLT. Pressure
      gradients were measured proximal and distal to the lesion, and gradient values >3
      mmHg were considered hemodynamically significant. We evaluated the technical
      success, complications, outcome of venoplasty and recurrence, and the patency
      rate. RESULTS: In all, 11 female patients manifested a pressure gradient >3 mmHg
      across the anastomotic site; they underwent subsequent PVT. The initial balloon
      venoplasty procedure was technically successful in 10 of the 11 patients (91%),
      and the pressure gradient was reduced from 5.8 to 1.1 mmHg (P < 0.01). Clinical
      improvement was observed in 9 of these 10 patients; one patient failed to improve
      and underwent retransplantation. Recurrent obstruction occurred in four patients;
      they underwent PTV with (n = 2) or without (n = 2) stent placement. There were no
      major procedural complications. CONCLUSION: PTV following venous pressure
      measurement is an effective and safe treatment for venous outflow obstruction in
      patients subjected to LDLT. In patients with recurrent obstruction, re-venoplasty
      is recommended.

PMID- 20799018
TI  - Magnetic resonance-guided vacuum-assisted breast biopsy: results in 100 Japanese
      women.
AB  - PURPOSE: The aim of this study was to clarify the frequency of malignancy and the
      histopathological characteristics of the lesions in patients undergoing magnetic
      resonance imaging (MRI)-guided vacuum-assisted biopsy (VAB). MATERIALS AND
      METHODS: A retrospective review of 100 consecutive patients with 102 lesions who
      had undergone MRI-guided VAB was performed. The biopsies were performed on a 1.5
      T MR scanner using a commercially available biopsy system. None of the lesions
      seen with MRI could be detected by mammography or second-look ultrasonography.
      RESULTS: The average lesion sizes of the focus, mass, and nonmass lesions before
      the biopsy were 4.5, 8.2, and 21 mm, respectively. Twelve patients (12%) had
      lesions located in the deep portion of the breast, close to the pectoral muscle.
      The biopsy was successfully performed without important side effects in all
      patients. Histopathological findings were invasive ductal carcinoma in 6 (6%), in
      situ carcinoma in 28 (27%), and high-risk and benign in 68 (67%). Two high-risk
      lesions were upgraded to ductal carcinoma in situ (DCIS), and three DCIS lesions
      were upgraded to invasive ductal carcinoma at surgical excision. CONCLUSION: The
      high rate of DCIS might be a unique feature among Japanese women. However, MRI
      guided VAB is necessary for MRI-only visible suspicious lesions in Japan.

PMID- 20799019
TI  - Computed tomography diagnosis of a primary aortoduodenal fistula in a patient
      with a partially thrombosed abdominal aortic aneurysm.
AB  - Primary aortoenteric fistula is a rare but fatal cause of gastrointestinal
      bleeding and requires urgent intervention. A high index of clinical suspicion in
      conjunction with imaging is required because a favorable outcome relies on prompt
      diagnosis. The primary forms of aortoduodenal fistulas are nearly always
      associated with abdominal aortic aneurysm, mostly atherosclerotic. Technological
      advances in imaging, particularly computed tomography (CT), play a pivotal role
      in the preoperative detection of these fistulas. We report the case of a 76-year
      old man who was diagnosed with a large abdominal aortic aneurysm with associated
      contained rupture and suggestion of an aortoduodenal fistula on CT. This case
      demonstrated the effectiveness, ease, and low cost of the preoperative evaluation
      and documentation of a primary aortoduodenal fistula using CT scans.

PMID- 20799020
TI  - Nuchal-type fibroma of the buttock: magnetic resonance imaging findings.
AB  - Nuchal-type fibroma, first described in 1988 by Enzinger and Weiss, is a rare
      fibrous growth occurring predominantly in the interscapular and paraspinous
      regions. It is typically located in the subcutaneous tissue of the posterior neck
      but may occur in extranuchal soft tissue sites such as the upper back, shoulder,
      and facial regions. In this article, we describe the magnetic resonance imaging
      findings of a nuchal-type fibroma that involved the buttock in a 45-year-old
      woman, and we review and discuss the literature on the subject.

PMID- 20799021
TI  - Ultrasonography-guided percutaneous transhepatic portacaval shunt creation.
AB  - We successfully created a percutaneous transhepatic portacaval shunt under
      ultrasonography (US) guidance in a 46-year-old man with refractory ascites. The
      shunt was created to salvage an attempt to create a transjugular intrahepatic
      portosystemic shunt (TIPS) that failed because of the elevated level of portal
      vein bifurcation due to alcoholic liver cirrhosis. Under US guidance, we
      simultaneously punctured the right branch of the portal vein and the inferior
      vena cava (IVC) using a two-step biliary drainage set. An Amplatz gooseneck snare
      was introduced transjugularly to retrieve the percutaneously inserted guidewire.
      The intrahepatic tract between the portal vein and the IVC was dilated using a
      balloon catheter, and a stent was placed in the tract. The patient showed
      complete resolution of ascites at discharge. We assume that our method is an
      alternative method for TIPS creation in patients with inadequate anatomical
      relations between the portal vein branches and the hepatic veins. This approach
      is thought to be feasible for patients with occluded or small hepatic veins.

PMID- 20799022
TI  - Malignant pleural mesothelioma detected by spontaneous pneumothorax.
AB  - We report a middle-aged man, without occupational or environmental exposure to
      asbestos, who presented with spontaneous pneumothorax. Computed tomography showed
      a 13-mm right apical mass. He underwent tumorectomy and was diagnosed with
      malignant pleural mesothelioma. A local recurrence with multiple and diffuse
      pleural involvement later appeared. The patient eventually underwent
      panpleuropneumonectomy, recovered well, and has been doing well for 18 months.

PMID- 20799023
TI  - Concurrent sublingual thyroid and thyroglossal cyst with functioning thyroid
      tissue in the absence of an orthotopic thyroid gland.

PMID- 20799024
TI  - [Inflammatory aortic aneurysms: Single center experiences with endovascular
      repair of inflammatory abdominal aortic aneurysms].
AB  - We report our single center experience of renal function, hydronephrosis and
      changes in perianeurysmal fibrosis (PAF) after endovascular repair (EVAR) of
      inflammatory abdominal aortic aneurysms (IAAA). A total of 6 patients were
      treated for IAAA with EVAR and the technical success was 100%. During the follow
      up period 5 patients showed regression of PAF and 1 patient showed minor
      progression of PAF on computed tomography scans. In 2 patients hydronephrosis was
      regressive postoperatively but no patients died within 30 days. There were no
      secondary complications to report and no secondary intervention was necessary. In
      the long-term course one patient exhibited complete regression of PAF.In
      appropriate cases EVAR is a safe method for aneurysm repair for IAAA. In patients
      with acute inflammation or hydronephrosis individual treatment concepts are
      required.

PMID- 20799025
TI  - [New aspects of MRI for diagnostics of large vessel vasculitis and primary
      angiitis of the central nervous system].
AB  - Vasculitis is a rare disease and clinical symptoms are often unspecific. Accurate
      and early diagnosis is mandatory in order to prevent complications, such as loss
      of vision or stroke. Imaging techniques can contribute to establishing a definite
      diagnosis and to evaluate disease activity and the extent of the disease in
      various vascular regions. Conventional imaging methods, such as computed
      tomography (CT) and magnetic resonance (MR) angiography, as well as digital
      subtraction angiography allow the vessel lumen but not the vessel wall to be
      depicted. However, vasculitis is a disease which primarily affects the vessel
      wall, therefore conventional imaging modalities often fail to make a definite
      diagnosis. Recently black-blood high resolution MR in vivo imaging has been used
      to visualize cervical and intracranial vasculitis. This review article presents
      imaging protocols for intracranial and cervical black-blood MR imaging and
      clinical cases with large vessel vasculitis and vasculitis of the central nervous
      system. Furthermore the current literature, examples of the most common
      differential diagnoses of cervical and cranial arteriopathy and the potential of
      other imaging modalities, such as PET/CT and ultrasound will be discussed.

PMID- 20799026
TI  - Effects of selective mineralocorticoid receptor antagonism on atrial ion currents
      and early ionic tachycardia-induced electrical remodelling in rabbits.
AB  - Over the past years, the importance of the renin-angiotensin-aldosterone system
      in atrial fibrillation (AF) pathophysiology has been recognised. Lately, the role
      of aldosterone in AF pathophysiology and mineralocorticoid receptor (MR)
      antagonism in "upstream" AF treatment is discussed. Hypothesising that selective
      MR antagonism might also influence atrial ion currents (L-type calcium current [I
      (Ca,L)], transient outward potassium current [I (to)], sustained outward
      potassium current [I (sus)]) and their tachycardia-induced remodelling, the
      effects of an eplerenone treatment were studied in a rabbit model. Six groups
      each with four animals were built. Animals of the control group received atrial
      pacing leads, but in contrast to the pacing groups, no atrial tachypacing (600
      per minute for 24 and 120 h immediately before heart removal) was applied.
      Animals of the eplerenone groups were instrumented/paced as the corresponding
      control/pacing groups, but were additionally treated with eplerenone (7 days
      before heart removal). Atrial tachypacing was associated with a reduction of I
      (Ca,L). I (to) was decreased after 24 h of tachypacing, but returned to control
      values after 120 h. In the absence of rapid atrial pacing, MR antagonism reduced
      I (Ca,L) to a similar extent as 120 h of tachypacing alone. Based on this lower
      "take-off level", I (Ca,L) was not further decreased by high-rate pacing. I (to)
      and its expected tachycardia-induced alterations were not influenced by MR
      antagonism. In our experiments, selective MR antagonism influenced atrial I
      (Ca,L) and its tachycardia-induced alterations. As changes of I (Ca,L) are
      closely linked with atrial calcium signalling, the relevance of these alterations
      in AF pathophysiology and, accordingly, AF treatment is likely and has to be
      further evaluated.

PMID- 20799027
TI  - [(3)H]-F13640, a novel, selective and high-efficacy serotonin 5-HT(1A) receptor
      agonist radioligand.
AB  - F13640 is a selective and high-efficacy serotonin 5-HT(1A) receptor agonist that
      demonstrates outstanding analgesic potential in different animal models. Here, we
      use the radiolabelled compound to further characterise its binding properties at
      5-HT(1A) receptors. F13640 was tritium-labelled to 47 and 64 Ci/mmol specific
      activity and used as radioligand at membrane preparations of CHO cells expressing
      human (h) 5-HT(1A) receptors. The K (d) of [(3)H]-F13640 was 1.8 nM at h5-HT(1A)
      receptors as determined from saturation binding experiments. In association time
      course experiments, k (obs) of [(3)H]-F13640 was 0.06 min(-1). Dissociation
      experiments performed in the presence of unlabelled F13640 as competing ligand
      yielded a k (off) value of 0.05 min(-1), resulting in a calculated K (d) of 1.4
      nM. In comparison, [(3)H]-8-OH-DPAT had a k (obs) of 0.50 min(-1), a k (off) of
      0.25 min(-1) and a calculated K (d) of 0.37 nM. Surprisingly, [(3)H]-F13640
      dissociation kinetics were distinctly slower in the presence of WAY-100635 and
      spiperone as competing ligands when compared with the agonist competitors, F13640
      and (+)8-OH-DPAT. The competitive binding profile of [(3)H]-F13640 with eight
      chemically diverse 5-HT(1A) receptor agonists and antagonists correlated highly
      (r = 0.996) with that of [(3)H]-8-OH-DPAT. In conclusion, [(3)H]-F13640 is a
      potent agonist radioligand at 5-HT(1A) receptors and may be a useful tool in
      pharmacological studies at native and recombinant 5-HT(1A) receptors. In
      addition, [(3)H]-F13640 dissociates more slowly from h5-HT(1A) receptors than
      [(3)H]-8-OH-DPAT, a kinetic property that might be related to its powerful
      analgesic effects as observed in vivo.

PMID- 20799029
TI  - Sediment toxicity in mid-continent great rivers (USA).
AB  - As part of the Environmental Monitoring and Assessment Program for Great River
      Ecosystems (EMAP-GRE), sediment samples were collected from 447 randomly selected
      littoral sites along the main channels of the Ohio, Missouri, and Upper
      Mississippi Rivers between 2004 and 2006. Toxicity of these sediment samples was
      measured using a 7-day Hyalella azteca survival and growth test. Sixty-five sites
      (14.5%) exhibited lethal toxicity, and 130 sites (29.1%) exhibited decreased
      growth. In the EMAP-GRE probabilistic sampling design, each sampled site had a
      weight associated with it that determined the length (and proportion) of the
      river represented by that sample point in the population. Weighted whole-river
      estimates indicated that of the 4721 river km sampled, sediment from 15.9 +/-
      3.0% of the river (752 +/- 50 km) were lethally toxic, 27.4 +/- 3.5% (1289 +/- 57
      km) were toxic by way of growth inhibition, and 40.0 +/- 3.7% (1887 +/- 68 km)
      exhibited either lethal or growth toxicity. Selected toxic samples were analyzed
      for 21 pesticides, 20 polychlorinated biphenyl congeners, and 6 polybrominated
      diphenyl ether congeners. For all of the samples tested, the concentration levels
      of these analytes were mostly lower than known toxicity thresholds, and neither
      unionized ammonia concentration nor osmotic stress (as measured by conductivity)
      could account for the toxicity found in sediments. The spatial pattern of
      sediment toxicity cannot be readily explained by urbanization or agricultural
      land use at the subcatchment scale. We speculate that the distribution of toxic
      sediment is more likely due to a combination of localized sources, including
      polluted tributaries, and the redistribution of contaminated sediments from
      upriver. The sediment toxicity results from this study will be used, in
      combination with other sediment, biologic, and habitat metrics and indicators
      collected in the EMAP-GRE study, to help interpret and assess the condition of
      the Ohio, Upper Mississippi, and Missouri Rivers.

PMID- 20799028
TI  - Efficacy of treatment with verbascoside, biotechnologically produced by Syringa
      vulgaris plant cell cultures in an experimental mice model of spinal cord trauma.
AB  - In this study we evaluated the effect of glycosylated phenylpropanoid
      verbascoside (VB), isolated from cultured cells of the medicinal plant Syringa
      vulgaris (Oleaceae) in experimental animal model of spinal cord injury (SCI). SCI
      was induced by the application of vascular clips to the dura via a four-level T5
      T8 laminectomy. SCI in mice resulted in severe trauma characterized by edema,
      tissue damage, and apoptosis. At 1 and 6 h after injury, the mice were treated
      with VB extract, administered at the dose of 2 mg/kg with intraperitoneal
      administration. Immunohistochemical examination demonstrated a marked increase on
      expression for nitrotyrosine, inducible nitric oxide synthase, poly(ADP-ribose),
      and apoptosis events (increase of Bax and Bcl-2 expression) in the spinal cord
      tissue. Additionally, we demonstrate that these inflammatory events were
      associated with the cytokines expression (TNF-alpha and IL-1beta), neutrophil
      infiltration (myeloperoxidase), and activation of NF-kappaB. In contrast, all of
      these parameters of inflammation were attenuated by treatment with VB. In a
      separate set of experiment, we have clearly demonstrated that VB treatment
      significantly ameliorated the recovery of function (evaluated by motor recovery
      score). Taken together, our results clearly demonstrate that treatment with VB
      extract reduces the development of inflammation and tissue injury events
      associated with spinal cord trauma.

PMID- 20799030
TI  - Successful emergent coronary thrombolysis in a neonate with Kawasaki's disease.
AB  - This report describes the case of a 29-day-old infant with Kawasaki's disease who
      presented in extremis with multiple coronary aneurysms and coronary thromboses,
      myocardial ischemia, and congestive heart failure. The infant successfully
      underwent emergent coronary thrombolysis with tissue plasminogen activator.

PMID- 20799031
TI  - Comparison of diagnostic performances of three different software packages in
      detecting coronary artery disease.

PMID- 20799033
TI  - Three-dimensional echocardiography and 153Sm-EDTMP SPECT/CT in extensive cardiac
      metastases from osteosarcoma.

PMID- 20799032
TI  - Development of new folate-based PET radiotracers: preclinical evaluation of 68Ga
      DOTA-folate conjugates.
AB  - PURPOSE: A number of (111)In- and (99m)Tc-folate-based tracers have been
      evaluated as diagnostic agents for imaging folate receptor (FR)-positive tumours.
      A (68)Ga-folate-based radiopharmaceutical would be of great interest, combining
      the advantages of PET technology and the availability of (68)Ga from a generator.
      The aim of the study was to develop a new (68)Ga-folate-based PET radiotracer.
      METHODS: Two new DOTA-folate conjugates, named P3026 and P1254, were synthesized
      using the 1,2-diaminoethane and 3-{2-[2-(3-amino-propoxy)-ethoxy]-ethoxy}
      propylamine as a spacer, respectively. Both conjugates were labelled with
      (67/68)Ga. Binding affinity, internalization and externalization studies were
      performed using the FR-positive KB cell line. Biodistribution and PET/CT imaging
      studies were performed in nude mice, on a folate-deficient diet, bearing KB and
      HT1080 (FR-negative) tumours, concurrently. The new radiotracers were evaluated
      comparatively to the reference molecule (111)In-DTPA-folate ((111)In-P3139).
      RESULTS: The K(d) values of (67/68)Ga-P3026 (4.65 +/- 0.82 nM) and (67/68)Ga
      P1254 (4.27 +/- 0.42 nM) showed high affinity for the FR. The internalization
      rate followed the order (67/68)Ga-P3026 > (67/68)Ga-P1254 > (111)In-P3139, while
      almost double cellular retention was found for (67/68)Ga-P3026 and (67/68)Ga
      P1254, compared to (111)In-P3139. The biodistribution data of (67/68)Ga-DOTA
      folates showed high and receptor-mediated uptake on the FR-positive tumours and
      kidneys, with no significant differences compared to (111)In-P3139. PET/CT
      images, performed with (68)Ga-P3026, showed high uptake in the kidneys and clear
      visualization of the FR-positive tumours. CONCLUSION: The DOTA-folate conjugates
      can be efficiently labelled with (68)Ga in labelling yields and specific
      activities which allow clinical application. The characteristics of the (67/68)Ga
      DOTA-folates are comparable to (111)In-DTPA-folate, which has already been used
      in clinical trials, showing that the new conjugates are promising candidates as
      PET radiotracers for FR-positive tumours.

PMID- 20799034
TI  - Coronary endothelial function: a clinical role for PET?

PMID- 20799035
TI  - EANM Dosimetry Committee guidance document: good practice of clinical dosimetry
      reporting.
AB  - Many recent publications in nuclear medicine contain data on dosimetric findings
      for existing and new diagnostic and therapeutic agents. In many of these
      articles, however, a description of the methodology applied for dosimetry is
      lacking or important details are omitted. The intention of the EANM Dosimetry
      Committee is to guide the reader through a series of suggestions for reporting
      dosimetric approaches. The authors are aware of the large amount of data required
      to report the way a given clinical dosimetry procedure was implemented. Another
      aim of this guidance document is to provide comprehensive information for
      preparing and submitting publications and reports containing data on internal
      dosimetry. This guidance document also contains a checklist which could be useful
      for reviewers of manuscripts submitted to scientific journals or for grant
      applications. In addition, this document could be used to decide which data are
      useful for a documentation of dosimetry results in individual patient records.
      This may be of importance when the approval of a new radiopharmaceutical by
      official bodies such as EMA or FDA is envisaged.

PMID- 20799036
TI  - Calculations for multi-type age-dependent binary branching processes.
AB  - This article provides a method for calculating the joint probability density for
      the topology and the node times of a tree which has been produced by an multi
      type age-dependent binary branching process and then sampled at a given time.
      These processes are a generalization, in two ways, of the constant rate birth
      death process. There are a finite number of types of particle instead of a single
      type: each particle behaves in the same way as all others of the same type, but
      different types can behave differently. Secondly, the lifetime of a particle
      (before it either dies, changes to another type, or splits into 2) follows an
      arbitrary distribution, instead of the exponential lifetime in the constant rate
      case. Two applications concern models for macroevolution: the particles represent
      species, and the extant species are randomly sampled. In one application, 1-type
      and 2-type models for macroevolution are compared. The other is aimed at Bayesian
      phylogenetic analysis where the models considered here can provide a more
      realistic and more robust prior distribution over trees than is usually used. A
      third application is in the study of cell proliferation, where various types of
      cell can divide and differentiate.

PMID- 20799037
TI  - Gene-gene interaction between tuberculosis candidate genes in a South African
      population.
AB  - In a complex disease such as tuberculosis (TB) it is increasingly evident that
      gene-gene interactions play a far more important role in an individual's
      susceptibility to develop the disease than single polymorphisms on their own, as
      one gene can enhance or hinder the expression of another gene. Gene-gene
      interaction analysis is a new approach to elucidate susceptibility to TB. The
      possibility of gene-gene interactions was assessed, focusing on 11 polymorphisms
      in nine genes (DC-SIGN, IFN-gamma, IFNGR1, IL-8, IL-1Ra, MBL, NRAMP1, RANTES, and
      SP-D) that have been associated with TB, some repeatedly. An optimal model, which
      best describes and predicts TB case-control status, was constructed. Significant
      interactions were detected between eight pairs of variants. The models fitted the
      observed data extremely well, with p < 0.0001 for all eight models. A highly
      significant interaction was detected between INFGR1 and NRAMP1, which is not
      surprising because macrophage activation is greatly enhanced by IFN-gamma and IFN
      gamma response elements that are present in the human NRAMP1 promoter region,
      providing further evidence for their interaction. This study enabled us to test
      the theory that disease outcome may be due to interaction of several gene
      effects. With eight instances of statistically significant gene-gene
      interactions, the importance of epistasis is clearly identifiable in this study.
      Methods for studying gene-gene interactions are based on a multilocus and
      multigene approach, consistent with the nature of complex-trait diseases, and may
      provide the paradigm for future genetic studies of TB.

PMID- 20799038
TI  - Optimising experimental design for high-throughput phenotyping in mice: a case
      study.
AB  - To further the functional annotation of the mammalian genome, the Sanger Mouse
      Genetics Programme aims to generate and characterise knockout mice in a high
      throughput manner. Annually, approximately 200 lines of knockout mice will be
      characterised using a standardised battery of phenotyping tests covering key
      disease indications ranging from obesity to sensory acuity. From these findings
      secondary centres will select putative mutants of interest for more in-depth,
      confirmatory experiments. Optimising experimental design and data analysis is
      essential to maximise output using the resources with greatest efficiency,
      thereby attaining our biological objective of understanding the role of genes in
      normal development and disease. This study uses the example of the noninvasive
      blood pressure test to demonstrate how statistical investigation is important for
      generating meaningful, reliable results and assessing the design for the defined
      research objectives. The analysis adjusts for the multiple-testing problem by
      applying the false discovery rate, which controls the number of false calls
      within those highlighted as significant. A variance analysis finds that the
      variation between mice dominates this assay. These variance measures were used to
      examine the interplay between days, readings, and number of mice on power, the
      ability to detect change. If an experiment is underpowered, we cannot conclude
      whether failure to detect a biological difference arises from low power or lack
      of a distinct phenotype, hence the mice are subjected to testing without gain.
      Consequently, in confirmatory studies, a power analysis along with the 3Rs can
      provide justification to increase the number of mice used.

PMID- 20799039
TI  - Choosing the nephrostomy size after percutaneous nephrolithotomy.
AB  - PURPOSE: To evaluate the effect of nephrostomy tube size on perioperative
      outcomes of percutaneous nephrolithtotmy (PCNL). METHODS: Forty-five well-matched
      patients with normal renal function were prospectively divided in two
      nonrandomized groups after uneventful PCNL (to receive either a 22-Fr, group 1 (n
      = 24 pts), or a 12-Fr nephrostomy tube, group 2 (n = 21 pts)). In all a balloon
      nephrostomy catheter with detachable funnel (Rusch Teleflex, Germany) was used. A
      Visual Analogue Scale (VAS) for measuring the pain was administered 8 and 24 h
      after the procedure. Postoperative analgesics use (Ketoralac Tromethamine 30 mg),
      pre- and postoperative Hb, renal function and urinary leaks were registered.
      RESULTS: Groups were comparable as demographics and stone characteristics. VAS
      pain score was significantly higher in group 1 (4.25 vs. 3.2, P < 0.001) only 8 h
      postoperatively. No significant difference was found in the VAS pain score 24 h
      p.o. Similarly, analgesics use (1.6 vs. 1.1, P = 0.05), sHb (1.42 vs. 1.21, P =
      0.055) and hospital stay (3.8 vs. 3.6, P = 0.63) were not significant between the
      two groups of patients. CONCLUSIONS: A small bore nephrostomy catheter may reduce
      pain in the immediate postoperative time. It does not affect blood loss and
      hospital stay so it can safely be used instead of a large size nephrostomy tube,
      after uneventful percutaneous procedures.

PMID- 20799040
TI  - Surgical versus non-surgical management of early stage oropharyngeal squamous
      cell carcinoma.
AB  - National guidelines state that early-stage oropharyngeal carcinoma can be treated
      by either primary surgery or radiotherapy. There is a paucity of evidence
      comparing surgery versus non-surgical therapy within the same population. With
      the shift in head and neck cancer treatment towards primary chemoradiation, the
      aim of this observational cohort study was to help define whether surgery still
      has a role for early-stage oropharyngeal disease, using a national prospective
      audit of all new head and neck cancers recruited between 1999 and 2001 in
      Scotland. Patients with T1-2 N0 M0 tumours were identified. Patients were divided
      into those treated surgically (+/-adjuvant radiotherapy) or non-surgically. Five
      year outcome data were calculated. Forty-two patients were treated surgically (13
      received adjuvant radiotherapy) and 32 patients treated non-surgically. Disease
      specific 5-year survival was 69 and 60%, respectively (p = 0.22). Locoregional
      failure occurred in seven of the surgical group and five of the non-surgical
      group. The success of chemoradiotherapy and the evidence for its use as adjuvant
      therapy may dissuade clinicians from considering surgical intervention. This
      study demonstrates the outcomes of surgical and non-surgical therapy within the
      same population. Where clear margins can be achieved, and in the absence of
      negative prognostic neck pathology, surgery remains a good option; allowing
      radiotherapy to be preserved for locoregional failures or second primary tumours.
      Although there are limitations to this study, it does demonstrate the benefit of
      prospective population data collection.

PMID- 20799041
TI  - Therapeutic options for treatment of Merkel cell carcinoma.
AB  - Merkel cell carcinoma (MCC) is a rare malignant neuroendocrine carcinoma of the
      skin. Owing to the aggressiveness of this tumor and the bad overall survival, we
      reviewed the therapeutic strategies, including surgery, radiation, and
      chemotherapy to find out the potentially best treatment option for one patient
      treated at our hospital. In addition, we investigated MCC biopsies using the
      FLAVINO assay to find out if individual chemoresponse testing might be a useful
      supplement in decision-making for the optimal therapeutic option for our MCC
      patient. The different results achieved using cisplatin, docetaxel, and cetuximab
      led to the conclusion that an individual chemoresponse testing in a predictive
      short-time assay might potentially be a useful diagnostic tool in identifying
      potentially effective chemotherapy treatments.

PMID- 20799042
TI  - In-season strength maintenance training increases well-trained cyclists'
      performance.
AB  - We investigated the effects of strength maintenance training on thigh muscle
      cross-sectional area (CSA), leg strength, determinants of cycling performance,
      and cycling performance. Well-trained cyclists completed either (1) usual
      endurance training supplemented with heavy strength training twice a week during
      a 12-week preparatory period followed by strength maintenance training once a
      week during the first 13 weeks of a competition period (E + S; n = 6 [? = 6]), or
      (2) usual endurance training during the whole intervention period (E; n = 6 [? =
      5, ? = 1]). Following the preparatory period, E + S increased thigh muscle CSA
      and 1RM (p < 0.05), while no changes were observed in E. Both groups increased
      maximal oxygen consumption and mean power output in the 40-min all-out trial (p <
      0.05). At 13 weeks into the competition period, E + S had preserved the increase
      in CSA and strength from the preparatory period. From the beginning of the
      preparatory period to 13 weeks into the competition period, E + S increased peak
      power output in the Wingate test, power output at 2 mmol l(-1) [la(-)], maximal
      aerobic power output (W (max)), and mean power output in the 40-min all-out trial
      (p < 0.05). The relative improvements in the last two measurements were larger
      than in E (p < 0.05). For E, W (max) and power output at 2 mmol l(-1) [la(-)]
      remained unchanged. In conclusion, in well-trained cyclists, strength maintenance
      training in a competition period preserved increases in thigh muscle CSA and leg
      strength attained in a preceding preparatory period and further improved cycling
      performance determinants and performance.

PMID- 20799044
TI  - Hydrogen peroxide sensor based on Prussian blue electrodeposited on (3
      mercaptopropyl)-trimethoxysilane polymer-modified gold electrode.
AB  - A hydrogen peroxide (H(2)O(2)) sensor was developed by electrodepositing Prussian
      blue (PB) on a gold electrode modified with (3-mercaptopropyl)-trimethoxysilane
      (MPS) polymer. The characterization of the self-assembled electrode was
      investigated by cyclic voltammetry and electrochemical impedance spectroscopy.
      The results of electrochemical experiments showed that such constructed sensor
      had a favorable catalytic ability to reduce H(2)O(2). The MPS film on the
      modified gold electrode greatly enhanced the pH-adaptive range of PB. Large
      surface-to-volume ratio property of double-layer 2d-network MPS-modified PB
      electrode enabled stable and highly sensitive performance of the non-enzymatic
      H(2)O(2) sensor. The linear range of H(2)O(2) determined is from 2.0 * 10(-6) to
      2.0 * 10(-4) mol L(-1) with a correlation coefficient of 0.9991 and a detection
      limit for H(2)O(2) of 1.8 * 10(-6) mol L(-1). The influences of the potentially
      interfering substances on the determination of H(2)O(2) were investigated. This
      modified electrode exhibits a good selectivity and high sensitivity with
      satisfactory results.

PMID- 20799043
TI  - The impact of acute strenuous exercise on TLR2, TLR4 and HLA.DR expression on
      human blood monocytes induced by autologous serum.
AB  - Acute exercise alters the surface expression of toll-like receptors (TLRs) and
      HLA.DR on blood monocytes, which could transiently compromise immunity. As serum
      factors might be responsible, we examined the effects of autologous post-exercise
      serum exposure on TLR2, TLR4 and HLA.DR expression on resting blood monocytes and
      their subtypes. Eight trained cyclists completed an ergometer 60 km time trial.
      PBMCs and serum were obtained before, immediately after and 1 h after exercise.
      TLR2, TLR4 or HLA.DR expression (gMFI) was determined on blood monocyte subtypes
      expressing combinations of CD14 and CD16 by flow cytometry, and on resting
      monocytes exposed to 50% autologous serum (pre, immediately after or 1 h after
      exercise) for 18 h in culture. Immediately after exercise, total monocyte
      expression of TLR2 and TLR4 increased by 41 and 27%, respectively, while HLA.DR
      expression was 39% lower than baseline. TLR2 and TLR4 was 53 and 84% greater 1 h
      after exercise, respectively, while HLA.DR was 48% lower. Changes in TLR2 and
      TLR4 expression occurred on the CD14(++bright)/CD16(+dim) monocyte subtype only,
      while HLA.DR expression changed on the CD14(+dim)/CD16(++bright) subtype. Serum
      did not affect monocyte TLR2 or TLR4 expression but 1 h post serum increased
      expression of HLA.DR on total monocytes and the CD14(+dim)/CD16(++bright)
      subtype, which was in contrast to the change observed at this time after
      exercise. We conclude that a bout of strenuous aerobic exercise alters the
      surface expression of TLR2, TLR4 and HLA.DR on blood monocytes and some of their
      subtypes, but these changes appear to be unrelated to blood serum factors.

PMID- 20799046
TI  - Elevated peritumoural rCBV values as a mean to differentiate metastases from high
      grade gliomas.
AB  - PURPOSE: Increased relative cerebral blood volume (rCBV) was previously found in
      peritumoural oedema of glioblastomas (GBM). Supposing that peritumoural rCBV is
      not increased in metastases, we aimed to evaluate whether rCBV values of the
      whole peritumoural area are accurate to differentiate solitary metastasis from
      GBM irrespective of the peritumoural oedema. METHODS: Contrast-enhanced T1
      weighted (T1-w) and T2*-weighted dynamic susceptibility contrast MRI was
      performed in 52 patients with contrast-enhancing solitary brain tumours before
      surgery. In each T1-w slice depicting the contrast-enhancing tumour, a rim within
      approximately 15 mm was defined in the peritumoural area. The rCBV values were
      normalised to rCBV values of the contralateral normal white matter. Differences
      between metastases and GBM for normalised rCBV values for each slice were
      determined with the Mann-Whitney U test (p < 0.05). RESULTS: Histopathological
      examination revealed 29 GBM and 23 metastases. Peritumoural rCBV was
      significantly lower in metastases than in GBM (p < 0.01). Using the cutoff value
      1.0 for discriminating metastases from GBM yielded a sensitivity of 96%,
      specificity of 64%, a positive predictive value of 68% and a negative predictive
      value of 95%. CONCLUSIONS: The rCBV in the peritumoural area of contrast
      enhancing brain tumours has a high diagnostic accuracy to discriminate metastases
      from GBM irrespective of surrounding oedema and without the bias of slice
      selection and ROI positioning. Metastases should be excluded, if at least one
      tumour-depicting slice reveals an increase of peritumoural rCBV compared to the
      normal contralateral brain (normalised rCBV value >1). Conversely, the decrease
      of peritumoural rCBV may not reliably exclude GBM.

PMID- 20799045
TI  - Management of a tumor in the distal trachea while maintaining spontaneous
      ventilation.
AB  - A 50-year-old man with carcinoma of the trachea presented for debulking. Due to
      the distal location of the tumor, a tracheostomy was not feasible. We were asked
      to provide general anesthesia but to maintain spontaneous ventilation. Sedation
      was provided with dexmedetomidine 0.7 MUg/kg per hour. Following induction with
      ketamine 2 mg/kg, the trachea was sprayed with 5 ml of 4% lidocaine and, with
      assistance from the surgeon, a CookTM Airway Exchange catheter was placed with
      the distal end just beyond the tumor. We then connected the proximal end to a
      manual jet ventilator to provide oxygen supplementation and, if necessary,
      positive-pressure ventilation. Subsequently, the surgeons were able to completely
      debulk the tumor and examine the airway down to the carina. Spontaneous
      ventilation was maintained throughout the case, with additional boluses of
      ketamine as necessary. The patient woke up after the procedure and had no
      delirium, nightmares, or recall. Dexmedetomidine worked synergistically with
      ketamine by preventing hypertension, hypersecretion, and postoperative delirium
      that is often seen when using ketamine alone. The successful use of ketamine and
      dexmedetomidine in this case demonstrates that this method may be applicable to
      other clinical situations where deep sedation and maintenance of spontaneous
      ventilation is required.

PMID- 20799047
TI  - Erythrocyte-protective effect of sarpogrelate hydrochloride (Anplag (r)), a
      selective 5-HT2 receptor antagonist: an in vitro study.
AB  - Sarpogrelate hydrochloride (Anplag((r)); Mitsubishi Tanabe Pharma Corporation,
      Osaka, Japan) is a selective S(2)-serotonergic receptor antagonist and is used as
      an antiplatelet agent. Sarpogrelate has been reported to increase erythrocyte
      deformability and suppress shear stress-induced hemolysis. In this study, we
      tested the protective effect of sarpogrelate on erythrocytes in an in vitro
      model. We compared the normalized index of hemolysis (NIH) between the group that
      was treated with sarpogrelate (n = 5) and the control group (n = 5) in a mock
      circulation under a shear force generated by a centrifugal pump. In the former
      group, 300 mg/day sarpogrelate was orally administered to a human volunteer for 2
      days before blood collection. The NIH was significantly lower in the sarpogrelate
      group than it was in the control group (0.0012 +/- 0.0009 vs. 0.0027 +/- 0.0005
      g/100 l, respectively; p = 0.016). Sarpogrelate suppressed shear stress-induced
      hemolysis in an in vitro model suggesting that sarpogrelate has a protective
      effect on erythrocytes under mechanical shear stress.

PMID- 20799048
TI  - Immune reconstitution to parvovirus B19 and resolution of anemia in a patient
      treated with highly active antiretroviral therapy.
AB  - Immune reconstitution inflammatory syndrome (IRIS) is an unsolved problem in the
      treatment of human immunodeficiency virus (HIV)-1 infection. Despite the high
      seroprevalence of parvovirus B19 (PVB19) among HIV-1-positive patients, reports
      on PVB19-induced anemia, especially that associated with PVB19-related IRIS, in
      these patients are limited. We present the case of a man with acquired
      immunodeficiency syndrome who developed severe transfusion-dependent anemia and
      was seropositive and borderline positive for immunoglobulin-M and IgG antibodies
      against PVB19, respectively. PVB19-DNA was also detected in his serum. The
      patient was diagnosed with pure red cell anemia (PRCA) caused by a primary PVB19
      infection and was treated with periodical blood transfusions. However, he
      subsequently tested negative for IgG antibodies and developed chronic severe
      anemia with high levels of PVB19 viremia. This indicated a transition from
      primary to persistent infection. After initiation of highly active antiretroviral
      therapy, the patient showed an inflammatory reaction with rapid deterioration of
      anemia and seroconversion of the IgG antibody to PVB19. Subsequently, PRCA was
      completely resolved, but the patient's serum still contained low levels of PVB19
      DNA. Thus, this was a case of IRIS associated with PVB19 infection. Our report
      highlights the significance of seroconversion to PVB19 in the diagnosis of IRIS
      and re-emphasizes the finding that persistently high levels of PVB19 viremia
      after primary infection are probably because of the lack of protective
      antibodies.

PMID- 20799049
TI  - Pharmacokinetic-pharmacodynamic study of itraconazole in patients with fungal
      infections in intensive care units.
AB  - Severely ill patients in intensive care units (ICU) are frequently at risk of
      developing fungal infections. Itraconazole (ITCZ), a triazole antifungal agent,
      is used for the treatment of aspergillosis, candidiasis, and cryptococcosis. The
      present retrospective pharmacokinetic-pharmacodynamic (PK-PD) analysis was
      designed to find any factors affecting clinical outcome of ITCZ treatment, and
      was performed to evaluate the appropriateness of the current dosage regimen in
      ICU patients. All of the patients admitted to Aichi Medical University Hospital
      ICU in 2008 who were treated with ITCZ injections for fungal infections were
      included in the study. After outcomes had been classified as cure or failure, a
      PK-PD analysis was performed. In addition, the probability of PD target
      attainment was assessed using a Monte Carlo simulation. Ten patients were
      enrolled in the study. Satisfactory outcomes were obtained in 4 of the 10
      patients. No significant differences in the area under the 24-h curve (AUC(0
      24)), peak concentrations and trough concentrations were observed between the two
      groups. However, it was observed that the higher the AUC(0-24), the better the
      outcome. Moreover, our results showed that additional dosage is needed to attain
      a sufficiently high AUC(0-24)/MIC in about 20% of patients. Our retrospective
      study is the first to show that it is important to consider the host's condition
      when ITCZ is administered, especially in ICU patients. The present findings are
      also useful for optimizing the individual dosage of ITCZ based on AUC(0-4) for
      the treatment of patients infected with Candida spp.

PMID- 20799051
TI  - Do no harm: a defense of markets in healthcare.
AB  - This paper argues that the rules that constitute a market protect autonomy and
      increase welfare in healthcare. Markets do the former through protecting rights
      to self-ownership and a cluster of rights that protect its exercise. Markets
      protect welfare by organizing and protecting trades. In contrast, prohibition
      destroys legitimate markets, giving rise to so-called black markets that harm
      both the autonomy and well-being of agents. For example, a fee-for-service
      medical system is a highly developed and specialized market. It is individuals
      working together, through the division of labor, to provide mutual insurance.
      This coordination, and the benefits it makes possible, is not possible without
      injunctions against harm. Prohibitions on harm are not mere ethical niceties,
      they are practice rules for both healthcare and markets. Placing the doctor
      within a healthcare market actually reinforces the doctor's moral obligation, and
      the legal enforcement of that obligation, not to harm. Similarly, markets
      reinforce patient rights to self-determination through legal and institutional
      enforcement of the harm principle in the form of the protection of certain basic
      welfare rights to life, bodily integrity, property, trade, and contract. Since
      the establishment of markets protects agent autonomy and welfare, and prohibition
      directly harms the same, there are strong reasons for establishing markets to
      protect trade in precisely those areas where autonomy and well-being are most
      vulnerable to exploitation, for example, the trade in human kidneys.

PMID- 20799053
TI  - Privacy and property in the biobank context.
AB  - A research biobank is a collection of personal health and lifestyle information,
      including genetic samples of yet unknown but possibly large information potential
      about the participant. For the participants, the risk of taking part is not
      bodily harm but infringements of their privacy and the harmful consequences such
      infringements might have. But what do we mean by privacy? Which harms are we
      talking about? To address such questions we need to get a grip on what privacy is
      all about and aim for a fruitful perspective on the issues of property and
      privacy rights in the context of biobanking. This paper argues that the limits
      and handling of private matters is determined in specific social relations. The
      crucial point is thus to determine which information and activities are or are
      not the legitimate concern of others. Privacy and property rights should be seen
      as balanced by duties, that is as inherently relational interests extending into
      the public sphere, rather than to see these rights as the control of an object-
      for instance the participant's biobank material.

PMID- 20799052
TI  - Privacy, public health, and controlling medical information.
AB  - This paper argues that individuals do, in a sense, own or have exclusive claims
      to control their personal information and body parts. It begins by sketching
      several arguments that support presumptive claims to informational privacy,
      turning then to consider cases which illustrate when and how privacy may be
      overridden by public health concerns.

PMID- 20799054
TI  - Commodification and privacy: a Lockean perspective.
AB  - This paper defends the thesis that privacy as a right is derived from fundamental
      rights to life, liberty, and property and does not permit restricting the
      commodification of bodily material; however, privacy as life, liberty, property
      does require conventions that ensure a robust and just market in bodily material.
      The analysis proceeds by defending a general commitment to liberty and markets,
      but not in the manner one might expect from a 'doctrinaire' libertarian. Ethical
      concerns about commodification are legitimate in the context of new medical and
      information technologies, but these concerns are not sufficiently well defined to
      justify political conclusions, since not every ethical concern is in itself a
      political concern, and the best way to resolve certain ethical difficulties is to
      draw up political boundaries that facilitate the discovery and testing of various
      solutions to our ethical puzzles. To illustrate the point, I will indicate how
      privacy as life, liberty, property defines such a dynamic solution to the
      problems of commodification of human bodily material and slippery information in
      insurance markets.

PMID- 20799055
TI  - Introduction: HEC Forum special issue on privacy and commodification.
AB  - The papers in this special thematic issue of HEC Forum critically and carefully
      explore key issues at the intersection of patient privacy and commodification.
      For example, should hospitals be required to secure a person's consent to any
      possible uses to which his discarded body parts might be put after his treatment
      or should it only be concerned with securing his informed consent to his
      treatment? Should a hospital be required to raise the possibility of the
      commodification of such (patient-discarded) body parts, or should it only be
      required to address this issue if the patient asks about it? Should persons be
      paid to engage in medical research, or should they only be compensated for their
      time, on the grounds, perhaps, that such payment would be coercive or
      exploitative, for it might move some persons to agree to participate in research
      who otherwise would not have done? This number of HEC Forum illustrates the
      widespread implications of these issues upon which healthcare ethics committees
      are called to deliberate.

PMID- 20799050
TI  - Stable transmission of reversible modifications: maintenance of epigenetic
      information through the cell cycle.
AB  - Even though every cell in a multicellular organism contains the same genes, the
      differing spatiotemporal expression of these genes determines the eventual
      phenotype of a cell. This means that each cell type contains a specific
      epigenetic program that needs to be replicated through cell divisions, along with
      the genome, in order to maintain cell identity. The stable inheritance of these
      programs throughout the cell cycle relies on several epigenetic mechanisms. In
      this review, DNA methylation and histone methylation by specific histone lysine
      methyltransferases (KMT) and the Polycomb/Trithorax proteins are considered as
      the primary mediators of epigenetic inheritance. In addition, non-coding RNAs and
      nuclear organization are implicated in the stable transfer of epigenetic
      information. Although most epigenetic modifications are reversible in nature,
      they can be stably maintained by self-recruitment of modifying protein complexes
      or maintenance of these complexes or structures through the cell cycle.

PMID- 20799056
TI  - Providing care for the "whole patient" in the cancer setting: the psycho-oncology
      consultation model of patient care.
AB  - This paper describes a psycho-oncology consultation model of care (POCM) that
      provides a framework for psychosocial clinical work with cancer patients. Goals
      for care are addressed that follow the recommendations of the Institute of
      Medicine report advocating care for the "whole patient." Specific goals include
      reducing distress and symptoms, building on the patient's existing strengths,
      enhancing self-efficacy, expanding the patient's repertoire of healthy coping
      strategies, and addressing informational needs. Specific interventions are
      described that clinicians can implement in order to address the above goals. The
      paper also addresses the unique challenges encountered in working with cancer
      patients, as well as programmatic difficulties that are inherent in providing
      mental health care in a medical setting.

PMID- 20799057
TI  - Multivariate information-theoretic measures reveal directed information structure
      and task relevant changes in fMRI connectivity.
AB  - The human brain undertakes highly sophisticated information processing
      facilitated by the interaction between its sub-regions. We present a novel method
      for interregional connectivity analysis, using multivariate extensions to the
      mutual information and transfer entropy. The method allows us to identify the
      underlying directed information structure between brain regions, and how that
      structure changes according to behavioral conditions. This method is
      distinguished in using asymmetric, multivariate, information-theoretical
      analysis, which captures not only directional and non-linear relationships, but
      also collective interactions. Importantly, the method is able to estimate
      multivariate information measures with only relatively little data. We
      demonstrate the method to analyze functional magnetic resonance imaging time
      series to establish the directed information structure between brain regions
      involved in a visuo-motor tracking task. Importantly, this results in a tiered
      structure, with known movement planning regions driving visual and motor control
      regions. Also, we examine the changes in this structure as the difficulty of the
      tracking task is increased. We find that task difficulty modulates the coupling
      strength between regions of a cortical network involved in movement planning and
      between motor cortex and the cerebellum which is involved in the fine-tuning of
      motor control. It is likely these methods will find utility in identifying
      interregional structure (and experimentally induced changes in this structure) in
      other cognitive tasks and data modalities.

PMID- 20799058
TI  - Effects of heterogeneity in synaptic conductance between weakly coupled identical
      neurons.
AB  - A significant degree of heterogeneity in synaptic conductance is present in
      neuron to neuron connections. We study the dynamics of weakly coupled pairs of
      neurons with heterogeneities in synaptic conductance using Wang-Buzsaki and
      Hodgkin-Huxley model neurons which have Types I and II excitability,
      respectively. This type of heterogeneity breaks a symmetry in the bifurcation
      diagrams of equilibrium phase difference versus the synaptic rate constant when
      compared to the identical case. For weakly coupled neurons coupled with identical
      values of synaptic conductance a phase locked solution exists for all values of
      the synaptic rate constant, alpha. In particular, in-phase and anti-phase
      solutions are guaranteed to exist for all alpha. Heterogeneity in synaptic
      conductance results in regions where no phase locked solution exists and the
      general loss of the ubiquitous in-phase and anti-phase solutions of the
      identically coupled case. We explain these results through examination of
      interaction functions using the weak coupling approximation and an in-depth
      analysis of the underlying multiple cusp bifurcation structure of the systems of
      coupled neurons.

PMID- 20799059
TI  - Feedback control strategies for spatial navigation revealed by dynamic modelling
      of learning in the Morris water maze.
AB  - The Morris water maze is an experimental procedure in which animals learn to
      escape swimming in a pool using environmental cues. Despite its success in
      neuroscience and psychology for studying spatial learning and memory, the exact
      mnemonic and navigational demands of the task are not well understood. Here, we
      provide a mathematical model of rat swimming dynamics on a behavioural level. The
      model consists of a random walk, a heading change and a feedback control
      component in which learning is reflected in parameter changes of the feedback
      mechanism. The simplicity of the model renders it accessible and useful for
      analysis of experiments in which swimming paths are recorded. Here, we used the
      model to analyse an experiment in which rats were trained to find the platform
      with either three or one extramaze cue. Results indicate that the 3-cues group
      employs stronger feedback relying only on the actual visual input, whereas the 1
      cue group employs weaker feedback relying to some extent on memory. Because the
      model parameters are linked to neurological processes, identifying different
      parameter values suggests the activation of different neuronal pathways.

PMID- 20799060
TI  - Online and offline sexual health-seeking patterns of HIV-negative men who have
      sex with men.
AB  - To inform health information targeting, we used cross-sectional data from 2577
      HIV-negative MSM to identify groups of men who access similar sources. Offline,
      more men reported talking to a physician about HIV than about having sex with
      men; fewer than half attended a safer sex workshop. Online, men sought
      information primarily through Internet search engines, GLBT websites, or health
      websites. A latent class analysis identified four groups of health seekers:
      minimal health seekers, those who accessed online sources only, those who sought
      information mostly from health professionals, and those who sought information
      from diverse sources. Minimal health seekers, 9% of the sample, were the group of
      greatest concern. They engaged in unprotected anal sex with multiple partners but
      infrequently testing for HIV or sought sexual health information. By encouraging
      health seeking from diverse sources, opportunities exist to increase men's
      knowledge of HIV/STI prevention and, when necessary, access to medical care.

PMID- 20799061
TI  - HIV incidence and prevalence among aboriginal peoples in Canada.
AB  - We examined incidence, prevalence, and correlates of HIV infection in Aboriginal
      peoples in Canada and found that among most risk groups both Aboriginal and non
      Aboriginal participants showed similar levels of HIV prevalence. Aboriginal
      peoples who use illicit drugs were found to have higher HIV incidence and
      prevalence when compared to their non-Aboriginal drug-using peers. Aboriginal
      street youth and female sex workers were also found to have higher HIV
      prevalence. Among Aboriginal populations, correlates of HIV-positive sero-status
      include syringe sharing and frequently injecting drugs, as well as geographic and
      social factors such as living in Vancouver or having a history of non-consensual
      sex. This study is relevant to Canada and elsewhere, as Indigenous populations
      are disproportionately represented in the HIV epidemic worldwide.

PMID- 20799063
TI  - Real world experience with cancer genetic counseling via telephone.
AB  - One barrier to genetic testing is the lack of access to genetic counselors. We
      provided cancer genetic counseling via telephone, through a pilot project for
      employees of a national health insurer, Aetna, Inc. Knowledge transfer,
      behavioral intentions, and patient satisfaction were assessed by survey after
      genetic counseling. Aetna sent an individual email to its employees nationwide
      notifying them of the availability of a new telephone genetic counseling and
      testing program and providing a link to take a brief screening questionnaire to
      determine whether they may be at risk of hereditary cancer. Employees completing
      the questionnaire received immediate feedback regarding whether there appeared to
      be a risk of hereditary cancer. If so, they were invited to schedule a telephonic
      genetic counseling session. After the session, respondents completed an online
      survey. 397 individuals completed the questionnaire. 39 proceeded with telephone
      genetic counseling, and 22 completed the follow-up survey, including all 11 women
      with family history warranting genetic testing. One third reported prior
      discussion about inherited cancer risk with their primary care provider (PCP);
      12% were referred to a geneticist; 20% had an accurate perception of their own
      cancer risk. After counseling, 94% reported understanding their risk for cancer
      and 87% were aware of available risk-reduction strategies. 87% of high-risk
      respondents intended to engage in risk-management interventions. 93% reported
      high satisfaction. 66% indicated they would not have pursued genetic counseling
      if it had not been available by phone. Results suggest telephone counseling is a
      viable option for increasing access to genetic experts. In this sample, telephone
      counseling increases knowledge of cancer risk, motivates intention to change
      health-related behaviors, and elicits a high satisfaction level. Consequently,
      Aetna now offers telephone cancer genetic counseling nationwide as a covered
      benefit.

PMID- 20799062
TI  - Understanding and using informants' reporting discrepancies of youth
      victimization: a conceptual model and recommendations for research.
AB  - Discrepancies often occur among informants' reports of various domains of child
      and family functioning and are particularly common between parent and child
      reports of youth violence exposure. However, recent work suggests that
      discrepancies between parent and child reports predict subsequent poorer child
      outcomes. We propose a preliminary conceptual model (Discrepancies in
      Victimization Implicate Developmental Effects [DiVIDE]) that considers how and
      why discrepancies between parents' and youths' ratings of child victimization may
      be related to poor adjustment outcomes. The model addresses how dyadic processes,
      such as the parent-youth relationship and youths' information management, might
      contribute to discrepancies. We also consider coping processes that explain why
      discrepancies may predict increases in youth maladjustment. Based on this
      preliminary conceptual framework, we offer suggestions and future directions for
      researchers who encounter conflicting reports of community violence exposure and
      discuss why the proposed model is relevant to interventions for victimized
      youths.

PMID- 20799069
TI  - Inhibitory effects of zingerone, a pungent component of Zingiber officinale
      Roscoe, on colonic motility in rats.
AB  - Ginger (rhizome of Zingiber officinale Roscoe) is an herbal medicine for the
      treatment of gastrointestinal disorders including constipation and diarrhea.
      Zingerone is a likely active constituent responsible for the antidiarrheal
      activity of ginger. The current study was designed to characterize
      pharmacological actions of zingerone on colonic motility. To evaluate
      pharmacological effects of zingerone on colonic motility, we used isolated
      colonic segments from rats, in which mechanical responses were recorded in the
      longitudinal direction. In addition, we evaluated the effects on colonic motility
      in vivo by measuring intraluminal pressure changes and expelled fluid volume from
      the colon in anesthetized rats. Zingerone was applied to the lumen of the colon
      to allow the drug to access from the mucosal side. Zingerone inhibited
      spontaneous contractile movements in the isolated colonic segments in a dose
      dependent manner. The inhibitory effects of zingerone on colonic movements were
      not affected by pretreatment with capsazepine, a typical antagonist of transient
      receptor potential vanilloid 1. In addition, tetrodotoxin, a blocker of voltage
      dependent sodium channels on neurons, did not affect the suppression of colonic
      movements by zingerone, suggesting that zingerone acts on the smooth muscles
      directly. Zingerone also attenuated colonic motility in vivo without affecting
      blood pressure and heart rate. The effects were reversible and reproducible. Our
      findings suggest that zingerone can inhibit colonic motility via direct action on
      smooth muscles. Zingerone might exert beneficial therapeutic effects on
      hypermotility-induced diarrhea by abrogating excessive gastrointestinal motility.

PMID- 20799071
TI  - Molecular cloning and expression of two cytosolic copper-zinc superoxide
      dismutases genes from Nelumbo nucifera.
AB  - Two cytosolic copper-zinc superoxide dismutase (cytCuZnSOD) complementary
      deoxyribonucleic acid were achieved in Nelumbo nucifera (Elian). The active sites
      and common characteristics of cytCuZnSOD family were showed by homology modeling.
      The two recombinant proteins expressed by PET-32a vector showed the similar SOD
      activity (89.94 +/- 0.54 U/mg) and could maintain more than 90% activity after
      incubation at 65 degrees C. The subcellular location by green fluorescent protein
      revealed that these two isoforms were all located in cytosol and nucleus. The
      cytCuZnSODs were expressed in various parts of N. nucifera, which were expressed
      highest in the leafstalks and young leaves and lowest in the roots. The
      cytCuZnSOD messenger ribonucleic acids isolated from wounded leaves significantly
      increased at 1.5 h after treatment (HAT) with the highest expression at 3 HAT,
      after which the level decreased.

PMID- 20799070
TI  - The roots of Nardostachys jatamansi inhibits lipopolysaccharide-induced endotoxin
      shock.
AB  - Nardostachys jatamansi (NJ) has been used in the treatment of inflammatory
      diseases. However, it is not clear how NJ produces anti-inflammatory effects. In
      the present study, using an experimental model of lipopolysaccharide (LPS)
      induced endotoxin shock, the protective effects and mechanisms of action of NJ
      were investigated. The water extract of roots of NJ was administrated to mice
      orally (1, 5, and 10 mg/kg) 1 h after or before LPS challenge. The administration
      of NJ inhibited LPS-induced endotoxin shock and the production of inflammatory
      mediators, such as interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)
      alpha, and interferon (IFN)-alpha/beta. Murine peritoneal macrophages were used
      to determine the production of inflammatory mediators. In peritoneal macrophages,
      NJ also inhibited LPS-induced production of inflammatory mediators, such as IL
      1beta, IL-6, TNF-alpha, and IFN-alpha/beta. In addition, NJ reduced the
      activation of mitogen-activated protein kinases (MAPKs) and the level of
      expression of interferon regulatory factor (IRF)-1 and IRF-7 mRNA. Furthermore,
      post-treatment with NJ reduced LPS-induced endotoxin shock and the production of
      inflammatory mediators. These results suggest that NJ inhibits endotoxin shock by
      inhibiting the production of IL-1beta, IL-6, TNF-alpha, and IFN-alpha/beta
      through the inhibition of MAPKs activation and IRF induction.

PMID- 20799072
TI  - Biodegradation of chlorinated and non-chlorinated VOCs from pharmaceutical
      industries.
AB  - Biodegradation studies were conducted for major organic solvents such as
      methanol, ethanol, isopropanol, acetone, acetonitrile, toluene, chloroform, and
      carbon tetrachloride commonly used in pharmaceutical industries. Various
      microbial isolates were enriched and screened for their biodegradation potential.
      An aerobic mixed culture that had been previously enriched for biodegradation of
      mixed pesticides was found to be the most effective. All the organic solvents
      except chloroform and carbon tetrachloride were consumed as primary substrates by
      this mixed culture. Biodegradation rates of methanol, ethanol, isopropanol,
      acetone, acetonitrile, and toluene were measured individually in batch systems.
      Haldane model was found to best fit the kinetics of biodegradation. Biokinetic
      parameters estimated from single-substrate experiments were utilized to simulate
      the kinetics of biodegradation of mixture of substrates. Among the various models
      available for simulating the kinetics of biodegradation of multi-substrate
      systems, competitive inhibition model performed the best. Performance of the
      models was evaluated statistically using the dimensionless modified coefficient
      of efficiency (E). This model was used for simulating the kinetics of
      biodegradation in binary, ternary, and quaternary substrate systems. This study
      also reports batch experiments on co-metabolic biodegradation of chloroform, with
      acetone and toluene as primary substrates. The Haldane model, modified for
      inhibition due to chloroform, could satisfactorily predict the biodegradation of
      primary substrate, chloroform, and the microbial growth.

PMID- 20799073
TI  - Neonatology is one of the most rapidly advancing fields of medicine.

PMID- 20799074
TI  - Pediatric hospitalizations associated with 2009 pandemic influenza A (H1N1): an
      experience from a tertiary care center in north India.
AB  - OBJECTIVES: To describe our experience in children hospitalized with the pandemic
      Influenza A (H1N1) from Northern India. METHODS: The retrospective case study was
      conducted at the Pediatric ward and Pediatric Intensive Care Unit (PICU)
      dedicated to the children (aged 18 years or younger) with influenza-like illness
      (ILI) with positive laboratory test results for pandemic H1N1 by reverse
      transcriptase polymerase-chain-reaction assay. RESULTS: Between August 2009 and
      January 2010, a total of 100 children were hospitalized with suspected 2009 H1N1
      influenza with Category "C" as described by the Government of India. Twenty five
      patients were positive for H1N1 and 9 for seasonal influenza A. The most common
      presentation (H1N1 positive) was with fever (100%), cough (100%), coryza (52%),
      respiratory distress (88%), vomiting (28%) and diarrhea (16%). One child
      presented with hypernatremic dehydration and seizures (Serum sodium 174 meq/l).
      Of the H1N1 positive hospitalized children, 7 (28%) had respiratory failure and
      required PICU admission, 4 (16%) required mechanical ventilation, and 3 (12%)
      died. The major radiological findings were bilateral pulmonary infiltrates and
      consolidation. All patients were treated with oral Oseltamivir suspension or
      capsule as per appropriate weigh band and supportive care as required. Two deaths
      were caused by refractory hypoxemia and one by refractory shock. CONCLUSIONS: The
      exact incidence of Pandemic 2009 H1N1 influenza on morbidity and mortality is
      difficult to calculate since only Category "C" patients were screened.

PMID- 20799075
TI  - Intensive care management of children with acute liver failure.
AB  - Acute liver failure is an uncommon condition associated with multi organ
      involvement, high morbidity and mortality. Etiology of acute liver failure varies
      with age and geographical location. Most cases of acute liver failure in India
      are due to infectious causes predominantly viral hepatitis. A significant group
      with indeterminate causation remains, despite careful investigation. The etiology
      of acute liver failure in infants is largely metabolic. The mainstay of
      management is supportive care in an intensive care unit. Monitoring of clinical
      and biochemical parameters is done frequently until the patient becomes stable.
      Mortality is predominantly due to raised intracranial pressure, infections and
      multi-organ failure. Liver transplant is an important life saving procedure for
      children with acute liver failure.

PMID- 20799076
TI  - Pulmonary interstitial emphysema complicating pneumonia in an unventilated term
      infant.
AB  - A case of pulmonary interstitial emphysema with pneumothorax and
      pneumomediastinum complicating pneumonia in a 6-week-old infant is reported. The
      patient had no history of resuscitation, bag and mask ventilation, nasal
      continuous positive airway pressure or mechanical ventilation.

PMID- 20799077
TI  - Preliminary report on neonatal screening for congenital hypothyroidism,
      congenital adrenal hyperplasia and glucose-6-phosphate dehydrogenase deficiency:
      a Chandigarh experience.
AB  - OBJECTIVE: To establish newborn screening in Indian scenario that could lay a
      framework for future such initiatives. Three disorders namely, congenital
      hypothyroidism (CH), congenital adrenal hyperplasia (CAH) and glucose-6-phosphate
      dehydrogenase deficiency (G-6-PDD) were selected for a preliminary study for
      newborn screening. METHODS: Heel-prick blood samples were collected from live
      born neonates at 24-48 h of birth as a part of a screening program after prior
      written consent from the parents. Blood levels of glucose-6-phosphate
      dehydrogenase enzyme (G-6-PD), thyroid-stimulating hormone (TSH) and 17-alpha-OH
      progesterone (17-OHP) were measured using DELFIA time resolved fluoroimmunoassay.
      RESULTS: Six thousand eight hundred and thirteen (6,813) neonates (86.3%), out of
      a total of 7,893 live births in our institute during the period May'2007 through
      July'2009, were screened for CAH, CH and G6PD deficiency. Major reason for
      missing samples was early discharge of the neonates and admission to the neonatal
      intensive care unit. G-6-PD deficiency was confirmed in 61 cases, congenital
      hypothyroidism (CH) in 2 cases and congenital adrenal hyperplasia (CAH) in 1
      neonate, accounting for an incidence of 1/112 for G-6-PDD, 1/ 3400 for CH and
      1/6813 for CAH. CONCLUSIONS: Preliminary data on prevalence of various genetic
      disorders viz. G-6-PDD, CH and CAH in the population of this region revealed that
      G-6-PDD is most prevalent disorder followed by CH and CAH. More efforts need to
      be undertaken to create awareness and emphasis on significance of preventive
      testing to make screening a successful program in India.

PMID- 20799078
TI  - Persistent diarrhea: risk factors and outcome.
AB  - OBJECTIVE: To identify risk factors associated with Persistent diarrhea (PD) and
      deaths due to PD. METHODS: This prospective case control study included 60
      children with PD (cases) and 60 children (controls) with acute diarrhoea (AD).
      Detailed history, examination and appropriate investigations were done for all
      children. Crude Odds ratio was calculated for each risk factor by univariate
      analysis and adjusted odds ratio was calculated by multivariate logistic
      regression. RESULTS: Prior antibiotic use, steroid use, anemia, vitamin A
      deficiency, malnutrition, LRI, UTI, oral candidiasis, and hyponatremia, were
      statistically significant risk factors by univariate analysis. Prior antibiotic
      use, vitamin A deficiency, malnutrition and LRI were independently associated
      with PD by multivariate logistic regression analysis. The risk factors for
      mortality were stool frequency more than 10 times per day, severe malnutrition,
      oral candidiasis, hypoalbuminemia and HIV positivity. CONCLUSIONS: The presence
      of these risk factors should alert the clinician to take appropriate measures, to
      decrease the mortality.

PMID- 20799079
TI  - Technetium-99m depreotide imaging by single photon emission tomography/low
      resolution computed tomography in malignant lymphomas: comparison with gallium-67
      citrate.
AB  - OBJECTIVE: Previous studies have demonstrated the feasibility of targeting
      lymphoma lesions with somatostatin receptor binding agents, mainly with In-111
      pentetreotide. In the present work another somatostatin analog, Tc-99m
      depreotide, is investigated. METHODS: One-hundred and six patients, 47 with
      Hodgkin's (HL) and 59 with various types of non-Hodgkin's lymphoma (NHL), were
      imaged with both Tc-99m depreotide and Ga-67 citrate. Planar whole-body and
      single photon emission tomography/low resolution computerized tomography
      (SPECT/CT) images were obtained. A total of 142 examinations were undertaken at
      different phases of the disease. Depreotide and gallium findings were compared
      visually and semi-quantitatively, with reference to the results of conventional
      work-up and the patients' follow-up data. RESULTS: In most HL, intermediate- and
      low-grade B-cell, as well as in T-cell NHL, depreotide depicted more lesions than
      Ga-67 and/or exhibited higher tumor uptake. The opposite was true in aggressive B
      cell NHL. However, there were notable exceptions in all lymphoma subtypes. During
      initial staging, 93.3% of affected lymph nodes above the diaphragm, 100% of
      inguinal nodes and all cases with splenic infiltration were detected by
      depreotide. On the basis of depreotide findings, 32% of patients with early-stage
      HL were upstaged. However, advanced HL and NHL cases were frequently downstaged,
      due to low sensitivity for abdominal lymph node (22.7%), liver (45.5%) and bone
      marrow involvement (36.4%). Post-therapy, depreotide detected 94.7% of cases with
      refractory disease or recurrence. Its overall specificity was moderate (57.1%).
      Rebound thymic hyperplasia, various inflammatory processes and sites of
      unspecific uptake were the commonest causes of false positive findings. The
      combination of depreotide and gallium enhanced sensitivity (100%), while various
      false positive results of either agent could be avoided. CONCLUSION: Except
      perhaps for early-stage HL, Tc-99m depreotide as a stand-alone imaging modality
      has limited value for the initial staging of lymphomas. Post-therapy, however,
      depreotide scintigraphy seems useful in the evaluation of certain anatomic areas,
      particularly in non-aggressive lymphoma types. The combination with Ga-67
      potentially enhances sensitivity and specificity. If fluorodeoxyglucose positron
      emission tomography is not available or in case of certain indolent lymphoma
      types, Tc-99m depreotide may have a role as an adjunct to conventional imaging
      procedures.

PMID- 20799080
TI  - New phylogenetic lineages of the Spirochaetes phylum associated with Clathrina
      species (Porifera).
AB  - Though spirochetes have been repeatedly found in marine sponges and other
      invertebrates, little attention has been paid to the specificity of this
      association. This study demonstrates that different geno-and morphotypes of
      spirochetes can reside within the same sponge individual and develop in
      considerable numbers. Specimens of the calcareous sponge Clathrina clathrus
      collected from the Adriatic Sea off Rovinj (Croatia) were found to harbor
      spirochete-like bacteria, which were characterized by scanning electron
      microscopy (SEM), 16S rRNA gene analysis, and catalyzed reporter deposition
      fluorescence in situ hybridization (CARD-FISH). Two novel spirochete sequence
      types related to the Brachyspiraceae could be retrieved. By use of specifically
      designed CARD-FISH probes, the C. clathrus-associated sequences could be assigned
      to a linear and a helical spirochete morphotype. Both were located within the
      sponge mesohyl and resembled the spirochete-like cells identified by SEM. In
      addition, from a Clathrina sp., most likely C. coriacea, that originated from
      Indonesian coastal waters, four different spirochete type sequences were
      recovered. Two of these also affiliated with the Brachyspiraceae, the other two
      were found associated with the Spirochaetaceae, one with the genera Borrelia and
      Cristispira.

PMID- 20799081
TI  - Development of a latex agglutination test for norovirus detection.
AB  - Norovirus (NoV) is the leading cause of acute gastroenteritis worldwide.
      Currently, reverse transcription polymerase chain reaction (RT-PCR) is used
      commonly to detect NoVs in both clinical and environmental samples. However, RT
      PCR requires expensive equipment and cannot be performed on site. In this study,
      a latex agglutination test (LAT) using antibody-labeled latex beads for detecting
      NoVs was developed. Two kinds of polyclonal antibodies, one generated from
      synthetic peptides and the other from E. coli-expressed NoV capsid proteins, were
      used to develop the LAT. Each of these polyclonal antibodies was immobilized on
      the surface of latex beads and tested for the ability to detect NoVs. Under
      optimized conditions, our LAT detected GII.4 NoV at concentrations as low as
      3.3x10(5) RT-PCR units/ml in stool samples. The detection limit for the LAT was
      approximately 1.7 103 RT-PCR units. Forty-eight stool samples were tested for
      NoVs using this LAT. In comparison with an RT-PCR assay, the sensitivity and
      specificity of the LAT were 35% and 100%, respectively. With further
      optimization, this LAT used with appropriate antibodies could be applied for
      convenient detection of NoVs in clinical diagnosis and food monitoring.

PMID- 20799082
TI  - Diversity of cold-active protease-producing bacteria from arctic terrestrial and
      marine environments revealed by enrichment culture.
AB  - A new approach for enrichment culture was applied to obtain cold-active protease
      producing bacteria for marine and terrestrial samples from Svalbard, Norway. The
      method was developed for the enrichment of bacteria by long-term incubation at
      low temperatures in semi-solid agar medium containing meat pieces as the main
      source of carbon and energy. ZoBell and 0.1x nutrient broth were added for marine
      and terrestrial microorganisms, respectively, to supply basal elements for
      growth. One to three types of colonies were observed from each enrichment
      culture, indicating that specific bacterial species were enriched during the
      experimental conditions. Among 89 bacterial isolates, protease activity was
      observed from 48 isolates in the screening media containing skim milk. Good
      growth was observed at 4 degrees C and 10 degrees C while none of the isolates
      could grow at 37 degrees C. At low temperatures, enzyme activity was equal to or
      higher than activity at higher temperatures. Bacterial isolates were included in
      the genera Pseudoalteromonas (33 isolates), Arthrobacter (24 isolates),
      Pseudomonas (16 isolates), Psychrobacter (6 isolates), Sphingobacterium (6
      isolates), Flavobacterium (2 isolates), Sporosarcina (1 isolate), and
      Stenotrophomonas (1 isolate). Protease activity was observed from
      Pseudoalteromonas (33 isolates), Pseudomonas (10 isolates), Arthrobacter (4
      isolates), and Flavobacterium (1 isolate).

PMID- 20799083
TI  - Aquimarina litoralis sp. nov., isolated from a coastal seawater.
AB  - A strictly aerobic, red-pigmented, non-motile, catalase- and oxidase-positive,
      Gram-staining-negative bacterium, designated strain CNURIC011(T), was isolated
      from seawater off the coast of Jeju Island in Korea. A phylogenetic analysis
      based on 16S rRNA gene sequences showed that strain CNURIC011(T) belongs to the
      genus Aquimarina in the family Flavobacteriaceae. 16S rRNA gene sequence analysis
      revealed that the close relatives of the novel strain are Aquimarina latercula
      ATCC 23177(T), Aquimarina marcrocephali JAMB N27(T), Aquimarina intermedia KMM
      6258(T), Aquimarina muelleri KMM 6020(T), and Aquimarina brevivitae SMK-19(T),
      with sequence similarities of 97.6, 96.6, 96.0, 95.6, and 94.2%, respectively.
      DNA-DNA hybridization revealed that the level of relatedness between strain
      CNURIC011(T) and Aquimarina latercula ATCC 23177(T) (=KCTC 2912(T)) was 4.9%. The
      DNA G+C content was 35.8 mol% and the major respiratory quinone was MK-6. The
      major fatty acids were iso-C(15:0) (14.9%), C(15:0) (13.9%), iso-C(17:0) 3-OH
      (12.6%), iso-C(15:1) G (7.3%), and iso-C(17:1) omega9c (7.2%). On the basis of
      phenotypic, phylogenetic, and genotypic data, strain CNURIC011(T) represents a
      novel species within the genus Aquimarina, for which the name Aquimarina
      litoralis sp. nov. is proposed. The type strain is CNURIC011(T) (=KCTC 22614(T)
      =JCM 15974(T)).

PMID- 20799084
TI  - Glycosylation and production characteristics of epothilones in alkali-tolerant
      Sorangium cellulosum strain So0157-2.
AB  - 3-O-alpha-D-ribofuranosyl epothilone A (epothiloneoside A) is a major component
      of glycosylated epothilones in Sorangium cellulosum strain So0157-2. The
      production and glycosylation ratios of epothiloneoside A in both solid and liquid
      culture conditions with various pH values and carbon sources were studied. The
      results showed that glycosylation occurs whenever epothilones are produced,
      regardless of changes in pH values, production time curves, and different carbon
      sources. We suggest that glycosylation is a stable process, paralleling the
      biosynthesis of epothilones in the So0157-2 strain.

PMID- 20799085
TI  - Patterns of survival and volatile metabolites of selected Lactobacillus strains
      during long-term incubation in milk.
AB  - The focus of this study was to monitor the survival of populations and the
      volatile compound profiles of selected Lactobacillus strains during long-term
      incubation in milk. The enumeration of cells was determined by both the Direct
      Epifluorescent Filter Technique using carboxyfluorescein diacetate (CFDA)
      staining and the plate method. Volatile compounds were analysed by the gas
      chromatography technique. All strains exhibited good survival in cultured milks,
      but Lactobacillus crispatus L800 was the only strain with comparable growth and
      viability in milk, assessed by plate and epifluorescence methods. The significant
      differences in cell numbers between plate and microscopic counts were obtained
      for L. acidophilus strains. The investigated strains exhibited different
      metabolic profiles. Depending on the strain used, 3 to 8 compounds were produced.
      The strains produced significantly higher concentrations of acetic acid, compared
      to other volatiles. Lactobacillus strains differed from one another in number and
      contents of the volatile compounds.

PMID- 20799086
TI  - Purification and characterization of the alpha-glucosidase produced by
      thermophilic fungus Thermoascus aurantiacus CBMAI 756.
AB  - An alpha-glucosidase enzyme produced by the fungus Thermoascus aurantiacus CBMAI
      756 was purified by ultra filtration, ammonium sulphate precipitation, and
      chromatography using Q Sepharose, Sephacryl S-200, and Superose 12 columns. The
      apparent molecular mass of the enzyme was 83 kDa as determined in gel
      electrophoresis. Maximum activity was observed at pH 4.5 at 70 degrees C. Enzyme
      showed stability stable in the pH range of 3.0-9.0 and lost 40% of its initial
      activity at the temperatures of 40, 50, and 60 degrees C. In the presence of ions
      Na(+), Ba(2+), Co(2+), Ni(2+), Mg(2+), Mn(2+), Al(3+), Zn(2+), Ca(2+) this enzyme
      maintained 90-105% of its maximum activity and was inhibited by Cr(3+), Ag(+),
      and Hg(2+). The enzyme showed a transglycosylation property, by the release of
      oligosaccharides after 3 h of incubation with maltose, and specificity for short
      maltooligosaccharides and alpha-PNPG. The K(m) measured for the alpha-glucosidase
      was 0.07 microM, with a V(max) of 318.0 micromol/min/mg.

PMID- 20799087
TI  - Bacillus megaterium strain XTBG34 promotes plant growth by producing 2
      pentylfuran.
AB  - Several chemical changes in soil are associated with plant growth-promoting
      rhizobacteria. An endosporeforming bacterium, strain XTBG34, was isolated from a
      Xishuangbanna Tropical Botanical Garden soil sample and identified as Bacillus
      megaterium. The strain's volatiles had remarkable plant growth promotion activity
      in Arabidopsis thaliana plants; after 15 days treatment, the fresh weight of
      plants inoculated with XTBG34 was almost 2-fold compared with those inoculated
      with DH5alpha. Head space volatile compounds produced by XTBG34, trapped with
      headspace solid phase microextraction and identified by gas chromatography-mass
      spectrometry, included aldehydes, alkanes, ketones and aroma components. Of the
      11 compounds assayed for plant growth promotion activity in divided Petri plates,
      only 2-pentylfuran increased plant growth. We have therefore identified a new
      plant growth promotion volatile of B. megaterium XTBG34, which deserves further
      study in the mechanisms of interaction between plant growth-promoting
      rhizobacteria and plants.

PMID- 20799088
TI  - Isolation and characterization of lactic acid bacteria strains with ornithine
      producing capacity from natural sea salt.
AB  - Two lactic acid bacteria (LAB) having ornithine-producing capacity were isolated
      from Korean natural sea salt. They were Gram-positive, short rod-type bacteria,
      and able to grow anaerobically with CO(2) production. The isolates grew well on
      MRS broth at 30-37 degrees C and a pH of 6.5-8.0. The optimum temperature and pH
      for growth are 37 degrees C and pH 7.0. The isolates fermented D-ribose, D
      galactose, D-lactose, D-maltose, Dcellobiose, D-tagatose, D-trehalose, sucrose, D
      melezitose, gentiobiose, D-glucose but not D-melibiose, inositol, and L-sorbose.
      The 16S rDNA sequences of the two isolates showed 99.5% and 99.6% homology with
      the Weissella koreensis S5623 16S rDNA (Access no. AY035891). They were
      accordingly identified and named as Weissella koreensis MS1-3 and Weissella
      koreensis MS1-14, and produced intracellular ornithine at levels of 72 mg/100 g
      cell F.W. and 105 mg/100 g cell F.W. and extracellular ornithine at levels of 4.5
      mg/100 ml and 4.6 mg/100 ml medium, respectively, by culturing in MRS broth
      supplemented with 1% arginine. High cell growth was maintained in MRS broth with
      a NaCl concentration of 0-6%. These results show for the first time that Korean
      natural sea salts contain lactic acid bacteria Weissella koreensis strains having
      ornithine producing capacity.

PMID- 20799089
TI  - DRA0336, another OxyR homolog, involved in the antioxidation mechanisms in
      Deinococcus radiodurans.
AB  - A novel OxyR (DR0615) with one conserved cysteine that senses hydrogen peroxide
      in Deinococcus radiodurans had been identified in our previous work. Comparative
      genomics revealed that D. radiodurans possesses another OxyR homolog, OxyR(2)
      (DRA0336). In this study, we constructed the deletion mutant of oxyR(2) and the
      double mutant of both the OxyR homologs to investigate the role of OxyR in
      response to oxidative stress in D. Radiodurans. Deletion of oxyR(2) resulted in
      an obviously increased sensitivity to hydrogen peroxide, and the double mutant
      for oxyR and oxyR(2) was significantly more sensitive than any of the two single
      mutants. The total catalase activity of the double mutant was lower than that of
      any of the single mutants, and reactive oxygen species (ROS) accumulated to a
      greater extent. DNA microarray analysis further suggested that oxyR(2) was
      involved in antioxidation mechanisms. Site-direct mutagenesis and complementation
      analysis revealed that C(228) in OxyR(2) was essential. This is the first report
      of the presence of two OxyR in one organism. These results suggest that D.
      radiodurans OxyR and OxyR(2) function together to protect the cell against
      oxidative stress.

PMID- 20799090
TI  - Differential expression profiles of Alternaria alternate genes in response to
      carbonyl sulfide fumigation.
AB  - Carbonyl sulfide (COS) is a new fumigant used in phytosanitary treatments. It was
      developed as a potential alternative to methyl bromide, which is being phased out
      because of its ozone-depletion properties. To understand the molecular and
      cellular mechanisms occurring in fungal pathogens in response to COS fumigation,
      we cloned 510 cDNA fragments of Alternaria alternata (Fr.) Keissler genes that
      are differentially expressed; these genes were cloned using suppression
      subtractive hybridization. Changes in the levels of transcripts of 79 fragments
      were confirmed by microarray analysis and qRT-PCR. Further homology search
      revealed that they are highly homologous to 41 genes of other fungi, which were
      related to general metabolism, growth and division, defense, cellular transport,
      and signal transduction. These results provide an overview of differential
      expression profiles of A. alternata genes following COS treatment and some new
      clues about the mechanism of COS fungitoxicity.

PMID- 20799091
TI  - Immunological responses induced by asd and wzy/asd mutant strains of Salmonella
      enterica serovar Typhimurium in BALB/c mice.
AB  - Attenuated bacteria have long been developed as vaccine candidates but can have
      some disadvantages, such as the potential for damage to immune organs due to
      insufficient clearance. To minimize these disadvantages, we generated Salmonella
      enterica serovar Typhimurium mutants SHJ2104 (asd::cm) and HTSaYA (wzy::km,
      asd::cm). The wzy gene codes for the O-antigen polymerase, which is involved in
      lipopolysaccharide (LPS) biosynthesis, and asd codes for aspartate beta
      semialdehyde dehydrogenase, which participates in cell wall formation. The
      strains synthesized LPS with a short-chain length, and showed lower cytotoxicity
      and reduced intracellular proliferation in animal cells compared to wild-type
      bacteria. After oral infection, the mutants were cleared in immune tissues,
      including the Peyer's patch, mesenteric lymph node, and spleen, within 5 days.
      The LD50 of the mutants in Balb/c mice was estimated to be 10(6) higher than wild
      type bacteria when administered either via an oral or i.p. route, indicating that
      the two strains are highly attenuated. To compare the immune response to and
      protective effects of the mutants against wild-type bacterial infection, we
      inoculated the mutants into mice via an oral (1x10(10)CFU) or i.p. (1x10(7) CFU)
      route once or twice at a two week interval. All immune responses, such as serum
      IgG and secretory IgA levels, cytokine production, and delayed hypersensitivity,
      were highly induced by two rounds of immunization. HTSaYA and SHJ2104 induced
      similar immune responses, and mice immunized with HTSaYA or SHJ2104 via an i.p.
      route were protected against wild-type Salmonella infection even at 100-fold of
      the LD(50) (5x10(6) CFU). Taken together, these data indicate that HTSaYA and
      SHJ2104 could be developed as live attenuated Salmonella vaccine candidates.

PMID- 20799092
TI  - Inhibitory effect of the essential oil from Chamaecyparis obtusa on the growth of
      food-borne pathogens.
AB  - In this study, the antibacterial activity of essential oil from Chamaecyparis
      obtusa (Sieb. et Zucc) leaves and twigs was investigated. The test strains were
      Klebsiella pneumoniae, Listeria monocytogenes, Salmonella typhimurium,
      Staphylococcus aureus, Escherichia coli, Legionella pneumophila, and Methicilline
      resistant Staphylococcus aureus. Antibacterial activity was estimated by
      measuring bacterial growth inhibition. Histopathological examination was also
      performed. C. obtusa oil distinctly inhibited the growth of all test strains and
      exhibited the strongest antibacterial activity against L. monocytogenes. It was
      chromatographically divided into several fractions. The fractions were further
      tested against antibacterial activity and their chemical compositions were
      analyzed. The fraction containing terpinen-4-ol (TA) showed high antibacterial
      activity toward all strains tested. Tests with authentic samples showed that TA
      played a major role in the antibacterial activity of C. obtusa oil, and in a mice
      test, the oil actively minimized inflammation by S. aureus.

PMID- 20799093
TI  - Characterization and identification of distinct Mycobacterium massiliense
      extracellular proteins from those of Mycobacterium abscessus.
AB  - Mycobacterium massiliense is an emerging pathogen and very similar to
      Mycobacterium abscessus of rapidly growing mycobacteria in the phenotype and
      genotype. Pathogenic bacteria secrete a diversity of factors into extracellular
      medium which contribute to the bacterial pathogenicity. In the present study, we
      performed the comparative proteome analysis of culture filtrate proteins from a
      clinical isolate of M. massiliense and M. abscessus strains using two-dimensional
      gel electrophoresis and liquid chromatography-electrospray ionization mass
      spectrometry (LC-ESI-MS). Interestingly, 9 proteins of M. massiliense were
      distinctly expressed from those of M. abscessus. Bioinformatic analysis of the
      identified proteins revealed that 3 unique proteins corresponded to
      serine/arginine rich protein, membrane protein from Streptomyces coelicolor, and
      one hypothetical protein from Corynebacterium efficiens YS-314, respectively.
      Culture filtrate proteins from M. massiliense induced the release of pro
      inflammatory cytokines from macrophages in a dose-dependent manner but not that
      from M. abscessus. Taken together, the functional study on the identified
      proteins uniquely produced from M. massiliense may provide not only the clues for
      the different pathogensis, but also help develop the diagnostic tools for the
      differentiation between two mycobacterial species.

PMID- 20799094
TI  - Newly identified CpG ODNs, M5-30 and M6-395, stimulate mouse immune cells to
      secrete TNF-alpha and enhance Th1-mediated immunity.
AB  - Bacterial CpG motifs are known to induce both innate and adaptive immunity in
      infected hosts via toll-like receptor 9 (TLR9). Because small oligonucleotides
      (ODNs) mimicking bacterial CpG motifs are easily synthesized, they have found use
      as immunomodulatory agents in a number of disease models. We have developed a
      novel bioinformatics approach to identify effective CpG ODN sequences and
      evaluate their function as TLR9 ligands in a murine system. Among the CpG ODNs we
      identified, M5-30 and M6-395 showed significant ability to stimulate TNF-alpha
      and IFN-gamma production in a mouse macrophage cell line and mouse splenocytes,
      respectively. We also found that these CpG ODNs activated cells through the
      canonical NF-kappa B signaling pathway. Moreover, both CpG ODNs were able to
      induce Th1-mediated immunity in Mycobacterium tuberculosis (Mtb)-infected mice.
      Our results demonstrate that M5-30 and M6-395 function as TLR9-specific ligands,
      making them useful in the study of TLR9 functionality and signaling in mice.

PMID- 20799095
TI  - Heterogeneous virulence potential and high antibiotic resistance of Pseudomonas
      aeruginosa strains isolated from Korean pneumonia patients.
AB  - Pseudomonas aeruginosa is an opportunistic human pathogen of clinical importance
      that causes airway infections in immunocompromised patients. Here, we report the
      virulence-associated characteristics of strains of P. aeruginosa, isolated from
      the sputa of 25 Korean pneumonia patients. A high degree of genomic plasticity
      was observed by random amplified polymorphic DNA genotype analysis, suggesting
      that the infections were caused by strains with diverse genomic backgrounds.
      Biofilm formation of each isolate was heterogeneous in terms of their relative
      motilities. In addition, 48% of isolates were defective in the production of 3
      oxo-C(12)-HSL (PAI-1), a quorum sensing signal molecule. In these strains, PAI-1
      dependent elastase production was correspondingly decreased, suggesting that a
      large number of strains were presumed to be quorum sensing deficient. Multidrug
      resistance (MDR) was seen in 56% of the isolates tested, and 44% of the MDR
      strains were resistant to five or more antibiotics. Taken together, our results
      provide additional insights into the virulence traits of P. aeruginosa clinical
      isolates, which will aid in treating P. aeruginosa infections in pneumonia
      patients.

PMID- 20799096
TI  - Effect of acidic pH on the invasion efficiency and the type III secretion system
      of Burkholderia thailandensis.
AB  - Burkholderia thailandensis is a close relative of Burkholderia pseudomallei.
      These organisms are very similar, but B. thailandensis is far less virulent than
      B. pseudomallei. Nucleotide sequencing and analysis of 14 B. thailandensis
      isolates revealed variation in the regions coding for the type III secreted BipD
      protein. The degree of B. thailandensis BipD sequence variation was greater than
      that found in B. pseudomallei. Western blot analysis indicated that, unlike B.
      pseudomallei, B. thailandensis type III secreted proteins including BipD and BopE
      could not be detected in the supernatant of culture medium unless induced by
      acidic conditions. In addition, culturing B. thailandensis under acidic growth
      conditions (pH 4.5) can induce the ability of this bacterium to invade human
      respiratory epithelial cells A549. The identification of an environmental
      stimulus that increases the invasion capability of B. thailandensis invasion is
      of value for those who would like to use this bacterium as a model to study B.
      pseudomallei virulence.

PMID- 20799097
TI  - Emergence of vancomycin-intermediate Staphylococcus aureus from predominant
      methicillin-resistant S. aureus clones in a Korean hospital.
AB  - The genetic and epidemiological features of four vancomycin-intermediate
      Staphylococcus aureus (VISA) isolates obtained from a Korean hospital were
      evaluated in this study. The VISA isolates were genotyped as sequence type (ST) 5
      staphylococcal cassette chromosome mec (SCCmec) II variant (n=2) and ST239-SCCmec
      III (n=2), which were derived from the predominant methicillin-resistant S.
      aureus (MRSA) clones in Korean hospitals. One VISA isolate was acquired during
      vancomycin treatment, whereas three VISA isolates were obtained from the patients
      who had not previously been exposed to glycopeptides. As VISA is likely to arise
      from the predominant MRSA clones and may then possibly spread between patients,
      the emergence of VISA should be monitored with great care in hospitals.

PMID- 20799098
TI  - Pedobacter yonginense sp. nov., isolated from a mesotrophic artificial Lake in
      Korea.
AB  - A non-motile red-pigmented bacterium, designated strain HMD1002(T), was isolated
      from an artificial lake located on the campus of Hankuk University of Foreign
      Studies, South Korea. The major fatty acids were iso-C(15:0) (29.6%), Summed
      Feature 3 (comprising C(16:1) omega7c and/or iso-C(15:0) 2-OH; 17.5%) and iso
      C(17:0) 3-OH (12.5%). The major isoprenoid quinone was menaquinone-7 (MK-7). The
      DNA G+C content was 41.0 mol%. A phylogenetic tree based on 16S rRNA gene
      sequences showed that strain HMD1002(T) formed a lineage in the genus Pedobacer
      and was closely related to Pedobacer terrae (96.3%) and Pedobacer suwonensis
      (95.8%) in sequence similarity. On the basis of the evidence presented in this
      study, strain HMD1002(T) represents a novel species of the genus Pedobacter, for
      which the name Pedobacter yonginense sp.nov. is proposed. The type strain is
      HMD1002(T) (=KCTC 22721(T) = CEC(T) 7544(T)).

PMID- 20799099
TI  - Evaluation of insecticidal activity of a bacterial strain, Serratia sp. EML-SE1
      against diamondback moth.
AB  - To identify novel bioinsecticidal agents, a bacterial strain, Serratia sp. EML
      SE1, was isolated from a dead larva of the lepidopteran diamondback moth
      (Plutella xylostella) collected from a cabbage field in Korea. In this study, the
      insecticidal activity of liquid cultures in Luria-Bertani broth (LBB) and
      nutrient broth (NB) of a bacterial strain, Serratia sp. EML-SE1 against thirty
      3rd and 4th instar larvae of the diamondback moth was investigated on a Chinese
      cabbage leaf housed in a round plastic cage (O 10 x 6 cm). 72 h after spraying
      the cabbage leaf with LBB and NB cultures containing the bacterial strain, the
      mortalities of the larvae were determined to be 91.7% and 88.3%, respectively. In
      addition, the insecticidal activity on potted cabbage containing 14 leaves in a
      growth cage (165 x 83 x 124 cm) was found to be similar to that of the plastic
      cage experiment. The results of this study provided valuable information on the
      insecticidal activity of the liquid culture of a Serratia species against the
      diamondback moth.

PMID- 20799100
TI  - Mental disorders in the pediatric setting - results of a Swiss survey.
AB  - THEORETICAL BACKGROUND: Mental disorders emerge in childhood and adolescence and
      are important risk factors for mental disorders in adolescence and adulthood.
      Since paediatricians are typically the first to see children with psychological
      problems, the aim of this study was to obtain a survey of mental disorders of
      children in paediatric settings. METHODS: 250 paediatricians completed a
      questionnaire especially developed for this study, which asked for the estimated
      frequency and type of mental disorders in their patients, assurance in
      identifying mental disorders, diagnostic and treatment strategies used for these
      disorders and requests for training. RESULTS: Paediatricians estimated that 15%
      percent of children in their paediatric setting reported psychological
      difficulties. The most frequent mental disorders indicated by the paediatricians
      were attention-deficit hyperactivity disorder (ADHD), anxiety disorders,
      depression and aggressive disorders. Comfort in assigning diagnoses for anxiety
      disorders and depression was lower than for externalizing disorders. Counselling
      was the treatment approach most often reported in treating mental disorders,
      followed by psychopharmacological medication. Psychotherapy, however, was
      reported very rarely. Paediatricians' wish for continuing education included
      diagnostics and screening instruments for psychological problems in childhood.
      CONCLUSIONS: Estimated prevalence rates reported by paediatricians are comparable
      with rates in epidemiological studies. As paediatricians are often confronted
      with psychological problems, they have the important role in recognising the
      early signs of mental problems.

PMID- 20799101
TI  - Outcomes of elderly hip fracture patients in the Swiss healthcare system: A
      survey prior to the implementation of DRGs and prior to the implementation ofa
      Geriatric Fracture Centre.
AB  - PROBLEM AND QUESTIONS: The consequences for elderly patients with hip fractures
      are well known. In Switzerland, the introduction of diagnosis related groups
      (DRG) will bring additional challenges. New models of care, such as Geriatric
      Fracture Centres (GFC), may be the key to minimising negative outcomes. This
      study documents outcomes of hip fracture patients in the Swiss healthcare system,
      for use as baseline data prior to DRG- and GFC-implementation, and compares them
      to results reported in the literature, for example by Cooper (1997). METHODS:
      This was a prospective cohort quality assurance survey with a one-year follow-up.
      Outcomes were mortality, living situation, required support and mobility. All
      patients 65 years of age or older with a proximal femoral fracture were included.
      Data were analysed by descriptive and interferential statistics. RESULTS: From
      272 patients, 70% were community dwelling pre-fracture. Overall, one-year
      mortality was 22%. Pre-fracture community dwelling patients had better outcomes
      than nursing home patients with a one-year mortality rate of 12%. A total of 83%
      of pre-fracture community dwelling patients still lived in the community after
      one year but more needed help with activities of daily living (ADL) or mobility.
      Patients with dementia, ADL- and mobility dependency pre-fracture were
      significantly more at risk for being newly admitted to a nursing home.
      CONCLUSIONS: Our results reflect the clinical reality of the hip fracture
      population in Switzerland. Results one year after fracture were comparable to
      study findings in different health care systems. Our findings provide important
      baseline data prior to the implementation of DRG and GFC.

PMID- 20799102
TI  - Impact of a normal or non-specific admission ECG on the treatment and early
      outcome of patients with myocardial infarction in Swiss hospitals between 2003
      and 2008.
AB  - BACKGROUND: Diagnosis of acute myocardial infarction (AMI) rests upon clinical,
      electrocardiographic and biochemical parameters. Previous studies reported AMI
      patients who present with non-specific ECGs. OBJECTIVES: To examine clinical or
      demographic features of AMI patients presenting with or without ECG changes and
      assess the impact of these ECGs on treatment and outcome. METHODS: Using the AMIS
      Plus data, patients admitted between 2003 and 2008 with a definite diagnosis of
      AMI (clinical symptoms, elevated troponin levels) were stratified according to
      the admission ECG into group 1 with normal/non-specific ECGs and group 2 with ECG
      changes. RESULTS: Of 14 957 patients, 1085 (7.3%) belonged to group 1 and 13 872
      (92.7%) to group 2. There were no differences between the two groups in age (65.9
      yr vs. 65.4 yr), gender (28% female), diabetes (19% vs. 18%), hypertension (61%
      vs. 59%), family history (35% vs. 33%) or smoking (37% vs. 38%). Dyslipidaemia
      (62% vs. 56%; p <0.001), history of CAD (39% vs. 35%; p = 0.023) and obesity (BMI
      >30 kg/m2 [23% vs. 19%; p = 0.003]) were more frequent in group 1 who were
      admitted longer after symptom onset (280 min vs. 230 min). Patients in group 1
      were exposed to less intensive pharmacological and interventional treatments
      (aspirin [93.6% vs. 95.3%; p = 0.012], clopidogrel [70% vs. 73%; p = 0.046],
      unfractionated heparin [59% vs. 65%; p <0.001], ACE inhibitors or angiotensin II
      antagonists [46% vs. 53%; p <0.001]). However, therapy with beta-blockers (72%
      vs. 70%), statins (75% vs. 76%) and nitrates (59% vs. 57%) did not differ between
      groups. Patients in group 1 underwent PCI significantly less frequently (69% vs.
      77%) with a longer hospital delay (589 min vs. 96 min). No differences were found
      for reinfarction (both 1.4%) and a cerebrovascular event (0.4% vs. 0.8%).
      Cardiogenic shock (5% vs. 2%; p <0.001) and mortality during hospitalisation were
      higher in group 2 (6% vs. 3%; p <0.001). A normal/non-specific ECG on admission
      was not an independent predictor of in-hospital mortality (OR 0.61; 95% CI 0.34
      1.11; p = 0.104). CONCLUSIONS: Despite less intensive treatment, AMI patients who
      presented with a normal/non-specific ECG developed cardiogenic shock less
      frequently during their hospitalisation and had a lower crude mortality rate
      compared to those with ECG changes on admission. Nevertheless, reinfarctions and
      cerebrovascular events occurred evenly in all AMI patients, regardless of their
      admission ECG.

PMID- 20799103
TI  - Stab wounds in a Swiss emergency department: a series of 80 consecutive cases.
AB  - BACKGROUND: Interpersonal violence is a worldwide social reality which seems to
      increasingly affect even the safest of countries, such as Switzerland. In this
      country, road traffic accidents, as well as professional and recreational
      activities, are the main providers of trauma-related injuries. The incidence of
      penetrative trauma related to stab wounds seems to be regularly increasing in our
      ED. The question arises of whether our strategies in trauma management are
      adapted to deal efficiently with these injuries. METHODS: To answer this
      question, the study analysed patients admitted for intentional penetrative
      injuries in a tertiary urban emergency department (ED) during a 23 month period.
      Demographics, conditions of the assault, injury type and treatments applied were
      analysed. RESULTS: Eighty patients admitted due to an intentional penetrating
      trauma accounted for 0.2% of the surgical practice of our ED. The assault
      occurred equally in a public or a private context, mainly affecting young males
      during the night and the weekend. Sixty six patients (83%) were treated as out
      patients. Only 10 patients needed surgery. None of them required damage control
      surgery. No patient died and the mean hospital stay was 5.5 days. CONCLUSIONS:
      The prevalence of stab wounds in Switzerland is low. These injuries rarely need
      complex, surgical procedures. Observational strategies should be considered
      according to the patient status.

PMID- 20799104
TI  - Simulated cataract and low contrast stimuli impair cognitive performance in older
      adults: implications for neuropsychological assessment and everyday function.
AB  - OBJECTIVE: To investigate how age-related declines in vision (particularly
      contrast sensitivity), simulated using cataract-goggles and low-contrast stimuli,
      influence the accuracy and speed of cognitive test performance in older adults.
      An additional aim was to investigate whether declines in vision differentially
      affect secondary more than primary memory. METHOD: Using a fully within-subjects
      design, 50 older drivers aged 66-87 years completed two tests of cognitive
      performance--letter matching (perceptual speed) and symbol recall (short-term
      memory)--under different viewing conditions that degraded visual input (low
      contrast stimuli, cataract-goggles, and low-contrast stimuli combined with
      cataract-goggles, compared with normal viewing). However, presentation time was
      also manipulated for letter matching. Visual function, as measured using standard
      charts, was taken into account in statistical analyses. RESULTS: Accuracy and
      speed for cognitive tasks were significantly impaired when visual input was
      degraded. Furthermore, cognitive performance was positively associated with
      contrast sensitivity. Presentation time did not influence cognitive performance,
      and visual gradation did not differentially influence primary and secondary
      memory. CONCLUSION: Age-related declines in visual function can impact on the
      accuracy and speed of cognitive performance, and therefore the cognitive
      abilities of older adults may be underestimated in neuropsychological testing. It
      is thus critical that visual function be assessed prior to testing, and that
      stimuli be adapted to older adults' sensory capabilities (e.g., by maximising
      stimuli contrast).

PMID- 20799105
TI  - Exploitation in older adults: personal competence correlates of social
      vulnerability.
AB  - Clinical assessment of older people at heightened risk of financial exploitation
      (also termed social vulnerability) is a difficult task. There are a number of
      previously untested domains of personal competence which could influence social
      vulnerability in later life. In this study, intellectual, cognitive, and social
      cognitive functioning was assessed in a combined sample of dementia patients
      (n=31) and neurologically healthy individuals (n=68) aged 50 years or over.
      Informants provided assessments of participants' social functioning, personality,
      and social vulnerability. In the combined sample, multiple regression analyses
      revealed significant relationships between each personal competence domain and
      (lower) social vulnerability, apart from personality which was non-significant.
      General cognitive functioning and, in particular, executive functioning showed
      significant overlap with social vulnerability after controlling for memory and
      age. Social measures were also important correlates of vulnerability, indicating
      that both neurocognitive and social cognitive deficits may contribute to
      financial exploitation in later life.

PMID- 20799106
TI  - The relationship between the Repeatable Battery for the Assessment of
      Neuropsychological Status (RBANS) and olfaction in patients referred for a
      dementia evaluation.
AB  - The current study examined the relationship between a standardized dementia
      battery (Repeatable Battery for the Assessment of Neuropsychological Status
      [RBANS]) and a test of olfactory discrimination (University of Pennsylvania Smell
      Identification Test [UPSIT]) in a heterogeneous sample of patients referred for a
      dementia assessment (N = 103). Significant moderate correlations were found
      between the UPSIT and each of the RBANS indexes, with the strongest correlation
      for Total Scale score, followed by the Delayed Memory Index and the Language
      Index. Significant moderate correlations were also found between the UPSIT and 11
      of the 12 subtests of the RBANS. While the major RBANS indexes demonstrated
      significant correlations with education and the Wechsler Test of Adult Reading, a
      measure of premorbid IQ, the UPSIT did not. This suggests the UPSIT may be
      sensitive to decline in dementia and largely unaffected by premorbid cognitive
      functioning. As a result, the UPSIT may provide neuropsychologists with an
      efficient, cost-effective, and sensitive supplement to a standard dementia
      battery.

PMID- 20799107
TI  - The Severe Impairment Battery predicts functional abilities in an inpatient
      geriatric population.
AB  - There is limited research examining the relationship between cognition in severe
      dementia and functional skills. The aim of the present study was to examine the
      relationship between the Severe Impairment Battery (SIB) and functional abilities
      as measured by the Assessment of Instrumental Function (AIF) in an acute
      inpatient geriatric psychiatry setting. Analyses showed significant correlation
      between the SIB and the AIF. Multiple regression demonstrated that SIB scores
      accounted for 44% of the variance in adaptive functioning. These results
      replicate some of the prior data examining the relationship between the cognition
      and functional abilities and extend these findings into the inpatient setting
      with more severely impaired patients.

PMID- 20799108
TI  - Memory malingering: evaluating WMT criteria.
AB  - The Word Memory Test (WMT) has been considered one of the best assessment tools
      for assessing memory malingering in spite of some reported false-positive
      results. Our goal was to examine the sensitivity and specificity of Green's 2003
      criteria for memory malingering using a Portuguese adaptation of the WMT. We
      applied the WMT to three groups of participants, including 20 healthy subjects
      asked to simulate memory impairment, 29 healthy adults asked to produce their
      best performance, and 21 patients with the diagnosis of mild cognitive impairment
      (MCI). Using Green's 2003 criteria, based on scores below cutoffs on the easy
      subtests, 67% of the MCI patients were classified as "poor effort." However, the
      sensitivity and specificity of the diagnosis could be raised to 95% using an
      alternative set of criteria, relying on comparisons between easy and hard subtest
      scores. We conclude that Green's original criteria based on easy subtest scores
      alone seem to be of low specificity for the diagnosis of memory impairment
      simulation, but the WMT is a good instrument for identifying simulation if the
      alternative criteria are applied.

PMID- 20799109
TI  - Prediction of depression and anxiety 1 year after moderate-severe traumatic brain
      injury.
AB  - This study examined three scales of the Personality Assessment Inventory (PAI;
      Anxiety, Anxiety-Related Disorders, and Depression) in 88 participants 1 year
      after they suffered a moderate-severe traumatic brain injury (TBI). Participants
      were all enrolled in the federally funded Traumatic Brain Injury Model System
      project at Carolinas Rehabilitation. The following variables were assessed at the
      time of injury: age, sex, employment and marital status, and length of loss of
      consciousness. Disability status, using the Disability Rating Scale (DRS), was
      assessed at the time of discharge from the rehabilitation hospital. A series of
      three linear regression analyses found that these variables significantly
      predicted scores on the Anxiety and Anxiety-Related Disorders scales, which
      accounted for 14% and 17.7% of the variance, respectively. The variables did not
      significantly predict scores on the Depression scale. Within each regression
      analysis, DRS was consistently and negatively related to each PAI scale, such
      that greater disability was associated with better psychological functioning.
      Such seemingly paradoxical findings are discussed in terms of anosognosia or poor
      awareness of psychological functioning among those with greater disability 1 year
      after TBI.

PMID- 20799110
TI  - Validation of a Mini-Mental State Examination (MMSE) for the Persian population:
      a pilot study.
AB  - The objective of the study was to develop and validate a translated and
      culturally adapted Mini-Mental State Examination (MMSE) for the Persian-speaking
      population. The MMSE was translated into Persian. Two groups of neurologically
      intact subjects (n = 100) and subjects with Alzheimer's disease (n = 13) were
      studied. The difference between groups on the mean total scores of the Persian
      MMSE was statistically significant (control = 28.62 +/- 2.09; subjects with
      Alzheimer's disease = 11.77 +/- 5.66; p < .001). The cutoff score of 23 was the
      best cutoff score for our subjects with a sensitivity and specificity of 98% and
      100%, respectively. There was a significant correlation between the Persian MMSE
      score and the level of education (r = .46) and with age (r = -.77). There was no
      significant correlation between the Persian MMSE and gender. The Persian MMSE was
      found to be valid for discrimination of cognitive impairment in the Persian
      speaking community.

PMID- 20799111
TI  - Validity of the Wechsler Test of Adult Reading (WTAR): effort considered in a
      clinical sample of U.S. military veterans.
AB  - The current study represents an examination of the construct validity of the
      Wechsler Test of Adult Reading (WTAR) among a sample of U.S. military veterans
      referred for outpatient neuropsychological evaluation that included a measure of
      negative response bias, namely, the Test of Memory Malingering (TOMM). This
      retrospective data analysis examined the relationship between the WTAR and
      measures of current verbal general intellectual function and current cognitive
      skills. Findings showed that, among patients passing the TOMM (N = 98), WTAR
      scores were most highly correlated with current verbal IQ but also showed
      significant correlations with verbal memory and lesser, but still significant,
      correlations with measures of visual-spatial memory. Discriminant validity for
      the WTAR was also shown among the group passing the TOMM in the sense that the
      WTAR, which is designed to measure verbal premorbid general intellectual skill,
      was not as highly correlated with measures of learning and memory as was a
      measure of current verbal general intellectual skill. Whereas scores on most
      study measures did significantly differ between the groups that passed versus
      failed the TOMM (N = 26), scores on the WTAR did not, suggesting that the WTAR
      may remain robust even in the face of suboptimal effort.

PMID- 20799112
TI  - Notation of professional qualifications and affiliations: avoiding puffery and
      deception.
AB  - Neuropsychologists are ethically charged with communicating their qualifications
      and credentials in ways that promote understanding and avoid deception. However,
      there exist few if any concrete guidelines about how and when to cite
      qualifications when rendering professional neuropsychological opinions. This
      article attempts to clarify the issues relevant to the signatory process,
      offering guidelines based on principles of accuracy, relevancy, and necessity.
      Common practices and problems are outlined, and recommended solutions offered.

PMID- 20799114
TI  - Putative mechanisms of cognitive dysfunction in chemotherapy-naive diffuse large
      B-cell lymphoma: a case report and review of the literature.
AB  - Cognitive impairment is now recognized as a frequent consequence of treatments
      for cancers localized outside the central nervous system (CNS). In contrast,
      little attention has been given to the potentially deleterious cognitive effects
      from non-CNS cancers themselves. The present case study proposes that cognitive
      deficits occur in a subset of treatment-naive patients with diffuse large B-cell
      lymphoma in whom no gross evidence of lymphoma-related CNS involvement is
      apparent. Evidence is presented from a case study and elaborate putative
      mechanisms centering on deleterious effects of B-cell-mediated inflammatory
      cytokine secretion on neurons. Moreover, this case study speculates that genetic
      variability involving apolipoprotein E or other factors may mediate cognitive
      variability among these patients.

PMID- 20799115
TI  - Wechsler Individual Achievement Test-III: what is the 'gold standard' for
      measuring academic achievement?

PMID- 20799117
TI  - InfarctSizer: computing infarct volume from brain images of a stroke animal
      model.
AB  - Many computational methods for determining the infarct volume from the image of
      2,3,5-triphenyltetrazolium chloride-stained brain slices rely on the discretion
      of the user to determine the infarct region by visual inspection. Once the user
      determines the infarct boundary by visual inspection, the methods compute the
      area within the boundary with the assumption that all the spots within the
      boundary have been infarcted at the same level. However, in the same brain image,
      partially infarcted spots often tend to appear pinkish whereas fully or severely
      infarcted spots appear white. We developed a program called InfarctSizer, which
      automatically detects the infarct region and computes the infarct volume
      proportional to infarction levels. Comparison of InfarctSizer with other methods
      shows that InfarctSizer computes the infarct volume more accurately and
      efficiently than other methods. InfarctSizer and sample brain images are
      available at http://wilab.inha.ac.kr/brainimage.

PMID- 20799119
TI  - Allocation of attentional resources in posthypnotic suggestion.
AB  - Highly hypnotizable subjects received a nonhypnotic instruction to respond to a
      particular digit in a display and a posthypnotic suggestion to respond to a
      different digit. On some test trials, these 2 responses were tested separately;
      on others, they were placed in conflict. Overall, subjects were no more
      responsive to posthypnotic cues than to nonhypnotic cues, nor did their response
      latencies differ. However, response to posthypnotic cues diminished when they
      conflicted with the nonhypnotic cues. Analysis of response latencies showed that
      posthypnotic responding interfered with nonhypnotic responding (and vice versa),
      even on those trials where there was no procedural conflict. Posthypnotic
      behavior is not inevitably evoked by the presentation of the prearranged cue.
      Furthermore, the interference between posthypnotic and nonhypnotic responses
      indicates that posthypnotic responding consumes attentional resources. Both
      findings indicate that posthypnotic behavior is not automatic in the technical
      sense of that term.

PMID- 20799118
TI  - 'I didn't feel like any of those things were me': results of a qualitative pilot
      study of race/ethnicity survey items with minority ethnic adolescents in the USA.
AB  - OBJECTIVE: The present study is a qualitative exploration of the thought
      processes of minority ethnic adolescents in responding to standard epidemiologic
      survey questions about racial/ethnic group membership in the USA. DESIGN: Fifteen
      minority ethnic adolescents (ages 15-21) were enrolled in a pilot qualitative
      study using a cognitive processing interview technique to elicit their
      understanding and interpretation of race/ethnicity survey items. RESULTS:
      Findings from this pilot study indicated that racial/ethnic classification survey
      items commonly used in the USA were susceptible to a number of item performance
      problems, including participant confusion, and misreported or insufficient
      responses. Additionally, item wording elicited intense affective reactions among
      participants. Results suggest the need for careful review of current US
      race/ethnic classifications systems, as standard survey measures are likely to
      provide an incomplete demographic characterization of minority ethnic
      adolescents. CONCLUSIONS: Recommendations are provided for improving procedures
      for collecting race and ethnicity data from youth in the USA.

PMID- 20799120
TI  - Trance state effects and imagery vividness before and during a hypnotic
      assessment: a preliminary study.
AB  - This preliminary study explored the relationship between imagery vividness before
      and during a hypnotic phenomenological assessment procedure, the Phenomenology of
      Consciousness Inventory-Hypnotic Assessment Procedure (PCI-HAP), while also
      assessing trance (hypnoidal) state effects and several other variables. The PCI
      HAP allows the assessment of trance state effects associated with hypnotism to be
      quantified and statistically assessed. The 102 subjects completed the PCI-HAP
      along with several other questionnaire items. Correlational and regression
      analyses suggested that imagery vividness during hypnotism (hypnotic imagoic
      suggestibility) was predicted by combined imagery vividness before hypnotism and
      trance (altered) state effects during hypnotism. When measuring several
      additional variables, imagery vividness during hypnotism was found to be a
      function of self-reported hypnotic depth and additional other variables. The
      usefulness of these results for better understanding imagery vividness before and
      during hypnotism is discussed.

PMID- 20799121
TI  - Long-term follow-up of self-hypnosis training for recurrent headaches: what the
      children say.
AB  - The author sent surveys to 178 consecutive youths previously referred for
      hypnosis for headaches. The survey sought current status of headaches: treatment,
      application of self-hypnosis, headache intensity, frequency, duration after self
      hypnosis, generalization of self-hypnosis to other problems, and attitudes
      regarding self-hypnosis and life stresses. Of 134 delivered surveys, 52 were
      returned complete. Years after treatment, 85% (44/52) reported continued relief
      with self-hypnosis, 44% (23/52) reported decreased headache frequency, 31%
      (16/52) noted decreased severity, and 56% (29/52) reported that self-hypnosis
      reduced headache intensity. Many (26/52) emphasized the value of self-hypnosis to
      life stresses. In children and adolescents, self-hypnosis is associated with
      significant improvement of headaches and with an enduring positive effect for
      many years following training. Results suggest common and spontaneous
      generalizability of self-hypnosis by young people to modulation of other problems
      in their lives.

PMID- 20799122
TI  - Polish norms for the Harvard Group Scale of Hypnotic Susceptibility, Form A.
AB  - The Polish version of the Harvard Group Scale of Hypnotic Susceptibility, Form A
      (HGSHS:A; Shor & Orne, 1962) was administered to 1174 participants (968 women and
      206 men). Polish data were compared with other norming studies. Point-biserial
      item-scale correlations ranged from r = .12 (posthypnotic suggestion item) to r =
      .49. The Kuder-Richardson correlation of .70 was within the range of the
      reference samples. Test-retest reliability coefficients were obtained from one
      group of participants tested twice in the same session (r = .69, p < .05), and
      another group 8 weeks apart (r = .58, p < .05). Females scored significantly
      higher than males.

PMID- 20799123
TI  - Autogenic training alters cerebral activation patterns in fMRI.
AB  - Cerebral activation patterns during the first three auto-suggestive phases of
      autogenic training (AT) were investigated in relation to perceived experiences.
      Nineteen volunteers trained in AT and 19 controls were studied with fMRI during
      the first steps of autogenic training. FMRI revealed activation of the left
      postcentral areas during AT in those with experience in AT, which also correlated
      with the level of AT experience. Activation of prefrontal and insular cortex was
      significantly higher in the group with experience in AT while insular activation
      was correlated with number years of simple relaxation exercises. Specific
      activation in subjects experienced in AT may represent a training effect.
      Furthermore, the correlation of insular activation suggests that these subjects
      are different from untrained subjects in emotional processing or self-awareness.

PMID- 20799124
TI  - Comparison of conventional therapies for dentin hypersensitivity versus medical
      hypnosis.
AB  - This study compared the efficacy of conventional treatments for dentin
      hypersensitivity (DHS) and hypnotherapy. During a 1-month period at an urban
      practice in a service area of approximately 22,000 inhabitants, all patients were
      examined. A total of 102 individuals were included in the evaluation. Values of
      186 teeth were analyzed. The comparison of the different treatment methods
      (desensitizer, fluoridation, and hypnotherapy) did not show significant
      differences in success rates. However, a noticeable difference was observed in
      terms of onset and duration of effect. For both desensitizer and hypnotherapy
      treatments, onset of effect was very rapid. Compared to the other methods
      studied, hypnotherapy effects had the longest duration. In conclusion,
      hypnotherapy was as effective as other methods in the treatment of DHS.

PMID- 20799125
TI  - Impact of a lecture about empirical bases of hypnosis on beliefs and attitudes
      toward hypnosis among Cuban health professionals.
AB  - The aim of this study was to examine whether a lecture on hypnosis can modify
      attitudes and misconceptions about hypnosis. The sample consisted of 97 health
      professionals from institutions in Havana City, Cuba. Group 1 consisted of 46
      participants who received a lecture on hypnosis. Group 2 consisted of 51
      participants who received a lecture about urology. and Beliefs toward Hypnosis
      Therapist was applied before and after the lecture. Results indicated that there
      were significant differences between the groups: Group 1 showed more positive
      attitudes toward hypnosis. However, both groups showed similar misconceptions
      about hypnosis and memory, which changed significantly in Group 1 after receiving
      the lecture about hypnosis but not in Group 2. Therefore, the lecture about
      hypnosis had a significant impact in correcting participants' misconceptions
      about memory and hypnosis.

PMID- 20799126
TI  - The effectiveness of hypnosis in reducing pain and suffering among women with
      metastatic breast cancer and among women with temporomandibular disorder.
AB  - The authors describe two studies of special interest to clinicians and clinical
      researchers. Both are randomized controlled studies, exclusively focused on
      female patients. The first study tests whether a year-long weekly group
      intervention including hypnosis can reduce cancer pain among women with
      metastatic breast cancer. Findings suggest the intervention slowed the increase
      in reported pain over a 12-month period relative to controls. The second study
      examines the effect of hypnosis in women suffering from temporomandibular
      disorder (TMD), with a special focus on function as well as pain. Hypnosis
      reduced TMD pain as measured by a numerical-rating scale.

PMID- 20799127
TI  - Cognitive-behavioral therapy for depression in bipolar disorder: a meta-analysis.
AB  - Given the prevalence of null hypothesis significance testing, cognitive
      behavioral therapy's effect on depressive symptoms of bipolar disorder is not
      fully understood in the absence of effect size statistics. The present study
      discusses the disadvantages associated with null hypothesis significance testing
      and seeks to overcome these shortcomings via conducting a meta-analysis which
      examines cognitive-behavioral therapy for depressive symptoms in persons with
      bipolar disorder. A systematic literature search was conducted and included
      articles were subject to meta-analytic procedures. With a mean weighted Cohen's d
      of -0.29, relative to treatment as usual, cognitive-behavioral therapy has a
      small effect on depressive symptoms in persons with bipolar disorder. The
      strengths, limitations, and need for future research are discussed.

PMID- 20799128
TI  - Prevention of adolescent reoccurring violence and alcohol abuse: a multiple site
      evaluation.
AB  - "Prevention of Adolescent Reoccurring Violence and Alcohol Abuse: A Multiple Site
      Evaluation" is a multiple component alcohol abuse and violent behavior prevention
      strategy, targeted to adolescents ages 16-21 who have high levels of anger, or
      who are victims/perpetrators of violence, and their families. Three community
      centers located in upstate New York provided group participants (N = 210) known
      to have conduct disorder and substance abuse history. The centers were used as
      the intervention sites over a seven-week period with the youth assessment staff
      using objective screening measures. The participants were exposed to a two
      pronged intervention, using a parental involvement cohort with approximately half
      of the study participants. The Teams, Games, and Tournaments strategy was the
      intervention method. Teams, Games, and Tournaments is a Social Learning Theory
      based intervention with demonstrated empirical evidence of the model's
      effectiveness. A 2 x 3 factorial design with two follow-up points encompassed:
      anger control, alcohol/substance abuse, and family interactive education. The
      goals of the study were to help adolescents reduce their alcohol use, to increase
      productive family interaction, and ultimately to reduce the adolescents'
      aggression levels and subsequently reduce the possibility of their becoming
      victims or perpetrators of a violent crime. Consistent with Social Learning
      Theory, the Teams, Games, and Tournaments treatment intervention makes use of
      adolescents as peer counselors. The practical implications include that
      professionals or students in our public schools, juvenile courts, correctional
      institutions, and residential treatment centers can easily implement this
      program. A standardized treatment manual is available. It offers a complete,
      ready-to-use, and cost-effective tool for reducing adolescent violence and
      alcohol abuse. Further, the data provide support for a hypothesis of social
      learning theory, that is: interventions using multiple components are more
      effective than single treatments on their own.

PMID- 20799129
TI  - An examination of the tripartite model of anxiety and depression in an outpatient
      sample of adolescents.
AB  - Anxiety and depressive disorders are the most common mental health problems for
      adolescents; understanding their etiology and course is necessary for developing
      effective prevention and treatment programs. The tripartite model of anxiety and
      depression was evaluated in a random, clinical sample of 185 adolescents, with an
      average age of 15.09 years (SD = 1.9), with 58.4% males (n = 108). Survey packets
      were mailed to participants (61% response rate). Two models were evaluated: (a)
      Model one fit adequately, however, modification indices and prior research and
      theory suggested adding paths between anxiety and depression. (b) Model two
      tested paths between anxiety and depression; this revised model fit the data
      well, suggesting a relationship from anxiety to depression. Further,
      physiological hyperarousal may be a distinct component for anxiety and negative
      affectivity may be a general risk factor for anxiety and depression in
      adolescents. The findings that different factors contribute to the cause of
      anxiety and depression have implications for practice.

PMID- 20799130
TI  - Evidence-based programs in school settings: barriers and recent advances.
AB  - In spite of multi-disciplinary calls for the use of evidence-based practice in
      schools, empirically supported interventions are not being implemented in most
      schools. To increase the use of evidence-based programs in schools, it may be
      necessary first to identify characteristics of those programs and other factors
      that represent barriers to their use. This study examined implementation
      requirements and the availability of program information of 51 school-based
      intervention programs. Analyses revealed implementation obstacles such as high
      start-up costs, challenging training and staffing requirements, and a lack of
      easily accessible information about programs. Research and practice implications
      of these findings are presented.

PMID- 20799131
TI  - Organizational and clinical implications of integrating an alcohol screening and
      brief intervention within non-substance abuse serving agencies.
AB  - Although there have been efforts to advance evidenced-based practices into
      community-based organizations the limited successes of dissemination and poor
      implementation of efficacious treatments within these organizations are beginning
      to be documented. This article builds on the knowledge gained from organizational
      research and those internal structures (e.g., culture and climate), which
      possibly impede or enhance evidenced-based practice implementation within
      community-based organizations. While there are many evidenced-based practices
      available to human services organizations, there seems to be a gap between
      research and the implementation of these clinical practices. Recommendations are
      provided to better enable community-based organizations to integrate evidenced
      based practice into its existing service structures.

PMID- 20799132
TI  - Neighborhood disadvantage and refusal of formal services among cases reported to
      adult protection services.
AB  - Research suggests that certain factors influence the way caregivers of older
      adults experience the role of caretaker. Aspects of the caregiving experience
      that have been considered include factors influencing decisions to seek services,
      causes of caregiver burden, and the relationship between caregiver burden and
      maltreatment. Most of this research has focused on characteristics of caregivers
      and how these individual characteristics influence the caregiving experience and
      subsequent maltreatment. Very little research, however, has examined the
      influence of contextual factors on the caregiving experience. This study
      considers how neighborhood context influences decisions to reject formal services
      among cases reported to Adult Protective Services. A specific focus is given to
      caregivers of persons with Alzheimer's and related diseases.

PMID- 20799133
TI  - Sex differences in post-coital behaviors in long- and short-term mating: an
      evolutionary perspective.
AB  - Few empirical studies have been devoted to exploring behaviors occurring
      immediately following sexual intercourse. Therefore, this study conducts an
      exploratory investigation of various post-coital behaviors that the authors
      propose may reflect the divergent adaptive reproductive strategies of each sex as
      understood from an evolutionary perspective. An online questionnaire was
      administered to 170 individuals examining sex differences in post-coital compared
      to pre-coital activities related to pair-bonding with long-term mates, as well as
      a variety of common post-coital activities comparing short- and long-term mating
      contexts. It was found that females were more likely than males to initiate and
      place greater importance on several behaviors related to intimacy and bonding
      following sex with long-term partners. Males were more likely to initiate kissing
      before sex, and females after sex. Intimate talk and kissing were rated by both
      sexes as more important before intercourse with a long-term partner, whereas
      cuddling and professing one's love was rated more important after sex. In a
      second set of more specific post-coital behaviors, females were more likely to
      engage in post-coital behaviors related to bonding with both short- and long-term
      partners, whereas males were more likely to engage in ones that were
      extrinsically rewarding or increased the likelihood of further coital acts.

PMID- 20799135
TI  - Remission of life-long stammering after posterior circulation stroke.
AB  - Developmental stammering is relatively common in the adult population. Stammering
      has a poor prognosis when it persists beyond adolescence and spontaneous or
      treatment-induced remission is very rare in adults. In this communication we
      report a case of life-long developmental stammering that resolved completely
      after the onset of a posterior circulation stroke and we speculate on the reason
      for this.

PMID- 20799134
TI  - Correlates of engaging in survival sex among homeless youth and young adults.
AB  - Using a sample of 1,625 homeless youth and young adults aged 10 to 25 from 28
      different states in the United States, this study examines the correlates of
      having engaged in survival sex. Findings suggest that differences exist based on
      demographic variables (gender, age, race, and sexual orientation), lifetime drug
      use (inhalants, ValiumTM, crack cocaine, alcohol, CoricidinTM, and morphine),
      recent drug use (alcohol, ecstasy, heroin, and methamphetamine), mental health
      variables (suicide attempts, familial history of substance use, and having been
      in substance abuse treatment), and health variables (sharing needles and having
      been tested for HIV). In addition to replicating previous findings, this study's
      findings suggest that African American youth; gay, lesbian, or bisexual youth;
      and youth who had been tested for HIV were significantly more likely to have
      engaged in survival sex than White, heterosexual youth, and youth who had not
      been tested for HIV, respectively. Implications for interventions with youth and
      suggestions for future research are discussed.

PMID- 20799136
TI  - American Diabetes Association--70th scientific sessions--research on novel
      therapeutics: part 1.
AB  - The American Diabetes Association 70th Scientific Sessions, held in Orlando, FL,
      USA, included topics covering new therapeutic developments in the field of
      diabetes research. This conference report highlights selected presentations on
      new research with novel agents. Investigational drugs discussed include the
      glucagon-like peptide-1 (GLP-1) agonist taspoglutide (Roche Holding AG/Teijin
      Ltd/ Chugai Pharmaceutical Co Ltd), the GLP-1 analog SKL-18287 (Sanwa Kagaku
      Kenkyusho Co Ltd), the sodium glucose transporter-2 (SGLT2) inhibitor ASP-1941
      (Astellas Pharma Inc/Kotobuki Pharmaceutical Co Ltd), the dual SGLT2/1 inhibitor
      LX-4211 (Lexicon Pharmaceuticals Inc), and the selective PPARgamma modulator INT
      131 (InteKrin Therapeutics Inc).

PMID- 20799137
TI  - American Diabetes Association--70th scientific sessions--research on novel
      therapeutics: part 2.
AB  - The American Diabetes Association 70th Scientific Sessions, held in Orlando, FL,
      USA, included topics covering new therapeutic developments in the field of
      diabetes research. This conference report highlights selected presentations on
      new research with novel agents. Investigational drugs discussed include the
      glucokinase activator SKL-19014 (Sanwa Kagaku Kenkyusho Co Ltd), the GPR119
      agonist AS-1535907 (Astellas Pharma Inc), the apical sodium-dependent bile
      transporter (ASBT) inhibitor SC-435 (Satiogen Pharmaceuticals Inc), the VEGF-A
      activator SB-509 (Sangamo BioSciences Inc), and the protein tyrosine phosphatase
      1b (PTP-1b) antisense inhibitor ISIS-113715 (ISIS Pharmaceuticals Inc).

PMID- 20799138
TI  - Asthma & COPD--IQPC's Second Conference.
AB  - The International Quality & Productivity Center's (IQPC) Second Asthma & COPD
      conference, held in Philadelphia, included topics covering new therapeutic
      developments in the field of asthma and COPD. This conference report highlights
      selected presentations on mAb treatments for asthma, including targeting IL-5, IL
      13, IL-9 and TNFa, CCR3 inhibitors, histamine H4 receptor inhibition, novel mouse
      models of COPD and inhaled antisense asthma therapies. Investigational drugs
      discussed include mepolizumab (GlaxoSmithKline plc), benralizumab (BioWa
      Inc/Kyowa Hakko Kirin Co Ltd/MedImmune LLC), AMG-317 (Amgen Inc/Takeda Bio
      Development Center Ltd), TPI-ASM-8 (Pharmaxis Ltd) and AIR-645 (Altair
      Therapeutics Inc).

PMID- 20799139
TI  - API Global Sourcing Strategies 2010.
AB  - The API Global Sourcing Strategies 2010 Conference, held in Berlin, included
      topics covering new developments in the field of global sourcing of active
      pharmaceutical ingredients (APIs). This conference report highlights selected
      presentations on development in Eastern API markets, specifically India and
      China, factors influencing changes in global API sourcing, and risk mitigation in
      API sourcing.

PMID- 20799140
TI  - European Neuroscience--Seventh Biennial FENS Forum.
AB  - The European Neuroscience--Seventh Biennial FENS Forum, held in Amsterdam,
      included topics covering new therapeutic developments in the field of
      neuroscience. This conference report highlights selected presentations on sodium
      channel inhibitors, ionotropic glutamate receptor antagonists, serotonin receptor
      modulators, and novel therapies for depression, pain and stroke. Investigational
      drugs discussed include ST-1936 (Sigma-Tau Industrie Farmaceutiche Riunite SpA),
      LY-392098 (Eli Lilly & Co) and Lu-AA21004 (H Lundbeck A/S/Takeda Pharmaceutical
      Co Ltd).

PMID- 20799141
TI  - ADMET--Fifth Annual SMi Conference.
AB  - SMi's fifth annual ADMET Conference, held in London, included topics covering new
      developments in the field of ADMET. This conference report highlights selected
      presentations on ADME optimization in drug discovery; targeting drugs to the
      brain; predicting bonds that might be attacked during metabolism; treating Caco-2
      membranes with vinblastine to enhance P-glycoprotein interactions; predictive
      ADMET in hit-to-lead optimization; structure-based studies of ADMET targets; an
      accelerated process for integrated drug development; building hypotheses in lead
      selection and optimization; supersaturation effects; the prediction of drug-drug
      interactions; developing a mechanism-based pharmacokinetic/pharmacodynamic model;
      drug transporter assays in drug discovery; time-dependent inhibition screens in
      early drug discovery; the system-dependent inhibition of CYP enzymes; the
      integrating predictive toxicology framework OpenTox; high-content analysis for
      predictive cytotoxicity testing; and emerging in vitro toxicity assays.

PMID- 20799142
TI  - The American Society for Virology--29th Annual Meeting.
AB  - The American Society for Virology 29th Annual Meeting, held in Bozeman, MT, USA,
      included topics covering new vaccine technologies, delivery methods and
      treatments in the field of virology. This conference report highlights selected
      presentations on human norovirus (HuNoV), SARS coronavirus and Rift Valley fever
      virus vaccine technologies; programmed cell death-1 (PD1) blockade and HyperAcute
      alpha-Gal platform technology methods; aerosol vaccination delivery; novel
      technologies to produce influenza virus-like particles (VLP) in mammalian cell
      lines; and investigational human rotavirus vaccines.

PMID- 20799143
TI  - International Society for Eye Research--XIXth Biennial Meeting.
AB  - The International Society for Eye Research--XIXth Biennial Meeting, held in
      Montreal, included topics covering new therapeutic developments in the field of
      eye disease research, including ocular oncology. This conference report
      highlights selected presentations on uveal melanoma and retinoblastoma.

PMID- 20799144
TI  - AIDS 2010--XVIII International AIDS Conference.
AB  - The AIDS 2010-XVIII International AIDS Conference, held in Vienna, included
      topics covering new therapeutic developments in the field of HIV therapy. This
      conference report highlights selected presentations on novel HIV entry
      inhibitors, reverse transcriptase inhibitors, integrase inhibitors and clinical
      trial data for an NRTI-based, antiviral, hyperactivation-limiting therapeutic.
      Investigational drugs discussed include GSK-1349572 (Viiv Healthcare/Shionogi &
      Co Ltd) and VS-411 (ViroStatics).

PMID- 20799145
TI  - Overcoming RNAi transduction in leukocytes using targeted and stabilized
      nanoparticles.
AB  - RNAi-based approaches have contributed significantly to the improved
      understanding of gene expression and function in vitro. The ability to apply
      these strategies in vivo to validate the role of specific genes in normal or
      pathological conditions, and to induce gene silencing, has led to new
      possibilities for using RNAi as a novel therapeutic modality. However, the
      translation of RNAi from an effective genomic tool into clinical applications has
      been hindered by the challenge of delivering RNAi molecules to their target
      tissues by systemic administration, particularly to hematopoietic cells. This
      feature review describes the current systemic RNAi delivery platforms targeted to
      leukocytes, with a focus on the integrin-targeted stabilized nanoparticles
      strategy, which uses leukocyte integrins for the delivery of siRNAs exclusively
      to cells of the immune system.

PMID- 20799146
TI  - The ABCs of cancer stem cell drug resistance.
AB  - Chemotherapy is generally effective as a non-targeted therapy in killing the
      majority of cells in a tumor; however, a small population of residual cells that
      are intrinsically resistant to such agents persist after chemotherapy, ultimately
      resulting in patient relapse. There is evidence that these cells within resistant
      tumors are cancer stem cells. A common mechanism of multidrug resistance used by
      residual tumor cells involves the expression of the ATP-binding cassette (ABC)
      transporters. Understanding the anticancer drug transport properties of these
      transporters, as well as their physiological functions, in addition to improved
      efforts to discover and characterize selective inhibitors, will lead to more
      effective therapeutics for oncology.

PMID- 20799147
TI  - Tivozanib, a pan-VEGFR tyrosine kinase inhibitor for the potential treatment of
      solid tumors.
AB  - Tivozanib (AV-951; KRN-951), being developed by AVEO Pharmaceuticals Inc and
      Kyowa Hakko Kirin Co Ltd, is an orally active, ATP-competitive, small-molecule,
      quinoline-urea derivative that inhibits VEGFR tyrosine kinase for the potential
      treatment of cancer. In particular, tivozanib is able to markedly inhibit the
      ligand-induced phosphorylation of VEGFR-1, VEGFR-2 and VEGFR-3 at picomolar
      concentrations. In preclinical studies, tivozanib produced a significant
      inhibition of tumor growth and angiogenesis in several different xenograft tumor
      models in athymic rats. In a phase I clinical trial, tivozanib was safe and
      tolerable when administered at oral doses up to 1.5 mg on a schedule of 4 weeks
      on, 2 weeks off treatment. Results from a phase II clinical trial in patients
      with advanced renal cell carcinoma reported an overall response rate of 25.4% and
      a median progression-free survival of 11.8 months in patients treated with
      tivozanib as a single agent. Hypertension and dysphonia were the most frequent
      adverse events. At the time of publication, a phase III clinical trial was
      recruiting patients with advanced renal cancer to assess tivozanib in comparison
      with sorafenib. Clinical trials are currently ongoing to evaluate the safety and
      antitumor activity of tivozanib in breast, lung and colorectal cancer. Tivozanib
      might represent a promising anticancer agent in several different tumor types.

PMID- 20799148
TI  - Iniparib, a PARP1 inhibitor for the potential treatment of cancer, including
      triple-negative breast cancer.
AB  - PARP inhibitors are a promising, novel class of anticancer agents. Iniparib (BSI
      201) is an intravenously administered PARP1 inhibitor under development by BiPar
      Sciences Inc, a subsidiary of sanofi-aventis, under license from Octamer Inc, for
      the potential treatment of cancer. Iniparib, either alone or in combination with
      chemotherapy, had significant antitumor activity in preclinical studies in vitro
      and in vivo. Phase I clinical trials in patients with solid tumors demonstrated
      that treatment with iniparib was associated with minimal toxicity. Encouraging
      results were observed in a randomized phase II clinical trial, which demonstrated
      that the addition of iniparib to gemcitabine and carboplatin led to an
      improvement in clinical benefit rate, progression-free survival and overall
      survival in patients with metastatic triple-negative breast cancer (TNBC)
      compared with gemcitabine and carboplatin alone. A phase III clinical trial to
      test the survival benefit of iniparib in combination with gemcitabine and
      carboplatin in metastatic TNBC has completed accrual. Another phase III clinical
      trial will evaluate the overall survival of patients with newly diagnosed stage
      IV squamous NSCLC treated with gemcitabine and carboplatin with or without
      iniparib. Several phase II clinical trials of iniparib as a single agent or in
      combination with chemotherapy are ongoing in other tumor types, such as ovarian
      and uterine cancer, NSCLC and glioblastoma. These trials will clarify the role of
      iniparib in the treatment of cancer, including TNBC.

PMID- 20799149
TI  - Social functioning and self-esteem in young people with disabilities
      participating in adapted competitive sport.
AB  - AIMS: The aim of this study was to investigate social functioning quality of life
      and self-esteem in young people with disabilities taking part in adapted
      competitive sport. METHOD: A sample of 496 athletes (mean age 16 years 4 months,
      range: 9 years to 20 years 9 months) was obtained from the 540 participants
      (91.8%) involved in a French national championship. The main outcome measurements
      were a social functioning inventory (PedsQL 4.0 social functioning) and a self
      esteem inventory in physical areas (physical self inventory 6 PSI-6). RESULTS:
      The mean PedsQL SF score was 74.6 (SD: 17.7). Comparisons of PedsQL SF according
      to gender, age, self mobility and training revealed no significant differences
      between the groups. PedsQL SF was weakly but significantly correlated with all
      subscales of the PSI-6 in the total population. PSI-6 scores were significantly
      different between boys and girls, with better self-esteem for boys on general
      self-esteem (7.7 vs. 6.9, P=0.018), physical condition (6.8 vs. 6.0, P=0.023) and
      attractive body subscores (6.5 vs. 5.1, P<0.001). CONCLUSION: Social functioning
      scores were significantly higher in this population than in the samples of young
      people with disabilities available in the literature. Interactions between self
      concept, social functioning quality of life and participation in adapted sport
      activities require further studies.

PMID- 20799150
TI  - Impact of long-term treatment of methylphenidate on height and weight of school
      age children with ADHD.
AB  - Stimulant-associated growth deficits in children with attention deficit
      hyperactivity disorder (ADHD) have long been a concern. We chose 146 school age
      children diagnosed with ADHD being treated with methylphenidate (MPH) and 29 drug
      free ADHD children, and followed them up for 2-4 years. We recorded the changes
      in height and weight after long-term methylphenidate treatment and analyzed the
      influence of confounding factors to growth in height, weight, and height
      velocity. The change of the gap between patients' height and mean height in the
      methylphenidate group was -1.86+/-0.82 cm ( P<0.001); in controls it was -0.26+/
      0.51 cm ( P<0.05). The changes of height standard deviation score (SDS) in the
      methylphenidate group and controls were -0.14+/-0.23 SD ( P<0.001) and +0.05+/
      0.10 SD ( P<0.05), respectively. The differences between the 2 groups were
      significant ( P<0.001). Both correlation and regression analyses indicated that
      the duration of treatment contributed significantly to the variance in change of
      height ( P<0.001). The height velocity was significantly attenuated in the first
      year. The change of the gap between the patients' weight and weight for height
      after methylphenidate was -0.14+/-1.25 kg ( P>0.05). From this study, a small but
      significant deceleration of height velocity has been identified as a long-term
      side effect of methylphenidate, the magnitude of the height deficit is related to
      the duration of treatment. Methylphenidate had no significant influence on weight
      and BMI values.

PMID- 20799151
TI  - Neurological manifestations in individuals with pure cutaneous or syndromic
      (Ruggieri-Happle syndrome) phenotypes with "cutis tricolor": a study of 14 cases.
AB  - BACKGROUND: The term cutis tricolor describes the combination of congenital hyper
      and hypo-pigmented skin lesions in close proximity to each other in a background
      of normal complexion. This phenomenon has been reported so far: (i) as pure
      cutaneous trait, (ii) as a part of a complex malformation syndrome (Ruggieri
      Happle syndrome--RHS), (iii) as a distinct type (cutis tricolor parvimaculata);
      (iv) in association with other (e. g., vascular) skin disturbances. AIM: The aim
      of this study was to define the spectrum of neurological abnormalities in cutis
      tricolor. METHODS: A retrospective and prospective 14-year study of clinical,
      electroencephalographic (EEG), neuroradiological (MRI), cytogenetic and ZFHX1B
      gene studies of 14 individuals (8 M, 6 F; aged 2-28 years) with cutis tricolor (4
      pure cutaneous; 10 syndromic) was undertaken. RESULTS: Neurological involvement
      was recorded in 71.4% (10/14) of the patients [100% (10/10) in RHS and null (0/4)
      in cases with isolated skin manifestations] and included psychomotor delay (n=8),
      seizures (n=9), EEG abnormalities (n=6), a behavioural phenotype (n=4), non
      specific brain abnormalities (n=6). Genetic analyses excluded ZFHX1B mutations
      and revealed a 19qter deletion (n=1). CONCLUSIONS: Even though we could not
      exclude the ascertainment and referral biases, we concluded that cutis tricolor
      may be a marker of underlying neurological involvement particularly in subjects
      with a syndromic (RHS) phenotype.

PMID- 20799152
TI  - Unusual neuroimaging in a young boy with cerebral X-linked adrenoleukodystrophy.
AB  - We describe the case of a 7-year-old boy with cerebral X-linked
      adrenoleukodystrophy presenting with neurobehavioral symptoms. Attention deficit
      with hyperactive behavior was followed by progressive memory retrieval deficits
      and difficulty in writing. A detailed review of the clinical history, clinical
      examination and contrast-enhanced brain nuclear magnetic resonance imaging
      disclosed indeed an atypical cerebral form of X-linked adrenoleukodystrophy with
      diffuse anterior and posterior white matter involvement with a typical rim of
      contrast enhancement. A severe clinical deterioration occurred despite dietary
      treatment and hormonal replacement therapy. These rare but severe forms of
      atypical cerebral X-linked adrenoleukodystrophy can more often mimic attention
      deficit/hyperactivity disorder and should, therefore, be considered in young
      males with progressive neurobehavioral symptoms, particularly when possibly
      related to frontal white matter involvement. An accurate clinical history and
      examination should determine whenever a contrast-enhanced head MRI should be
      indicated.

PMID- 20799153
TI  - Malignant progression of a pleomorphic xanthoastrocytoma in a child.
AB  - Pleomorphic xanthoastrocytoma (PXA) is a recently recognized rare cerebral
      neoplasm that predominantly affects young patients. We report on the case of a 3
      year-old boy who presented with a 2-week history of headaches and seizures.
      Radiological investigation revealed a lesion in the right parietal-occipital
      lobe. The lesion was excised and histology disclosed the presence of a PXA with
      anaplastic features. 1 year later follow-up magnetic resonance imaging (MRI)
      revealed tumor relapse. An MRI of the spine was also performed and demonstrated
      leptomeningeal dissemination. The patient underwent a second operation. Histology
      revealed that the presence of a malignant PXA with anaplastic features. The
      patient received radiotherapy and 9 months later on follow-up MRI a new tumor
      recurrence was noted. A third craniotomy was performed and the tumor removed.
      Histological examination revealed dedifferentiation to glioblastoma multiforme.
      The patient was referred to the oncology department and received chemotherapy
      with temozolamide. 8 months later the patient was stable without tumor
      recurrence. PXAs require close follow-up because of their unpredictable
      biological behaviour.

PMID- 20799154
TI  - Disruption of endothelial tight junctions in a patient with mitochondrial
      encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS).
AB  - An electron microscopic study revealed disruption of capillary endothelial tight
      junctions (TJs) in both biopsied muscle, taken at 5 years and 1 month of age, and
      the autopsied brain, taken at 13 years and 6 months of age, in a patient with
      mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS)
      and mitochondrial DNA (mtDNA) point mutation A3243G. This endothelial barrier
      disruption might result in vasogenic edema and systemic lactic acidosis, possibly
      the critical pathology of MELAS.

PMID- 20799155
TI  - [Hearing loss after taking a header into water].

PMID- 20799156
TI  - [Hoarseness in patient with systemic lupus erythematosus].

PMID- 20799157
TI  - [Laryngeal reconstruction after resection of a subglottic adenocarcinoma].

PMID- 20799158
TI  - [Ocular manifestations in xeroderma pigmentosum].
AB  - BACKGROUND: The aim of this study was to evaluate ocular changes in patients with
      xeroderma pigmentosum (XP) and Cockayne syndrome (CS). Both diseases belong to
      the progeroid syndromes caused by single gene mutations with premature aging.
      Both syndromes are very rare autosomal recessive diseases caused by a gene defect
      leading to deficient DNA repair. PATIENTS: 12 patients (4 female, 8 male) with XP
      between 3 and 67 years old and a 39-year-old female patient with CS were
      examined. The examination included visual acuity testing, slit lamp
      biomicroscopy, funduscopy and performance of a Schirmer test. RESULTS: Changes of
      the lids in the XP group included blepharitis in 7 patients, distichiasis in 2,
      and madarosis in 3 patients. 8 patients had multiple lentigines solares of the
      lids. One patient showed scars of the lower lids after excision of a squamous
      cell carcinoma and a basal cell carcinoma. Conjunctival lesions comprised a
      tumour of unknown origin of the conjunctiva in 1 patient, teleangiectasia of the
      conjunctiva in 5 patients, pterygia in 4, and pinguecula in 1 patient. Two
      patients had an intraepithelial melanosis of the conjunctiva, and one showed
      conjunctival nevi. Two patients had corneal scars and corneal vascularisation,
      another a significant conjunctivalisation of the cornea. A Schirmer test was
      feasible only in 3 patients. Tear production was markedly reduced in all these
      patients. Break-up time was shortened significantly in 6 patients examined. The
      patient with the CS showed atrophy of the pupillary rim and a subcapsular
      cataract. Funduscopically there were pigment epithelial changes. CONCLUSIONS:
      Patients with XP often exhibit ocular changes. Beside the light-dependent
      degenerative and inflammatory manifestations at the lids, the conjunctiva and the
      cornea patients with XP also develop malignancies early in life. The majority of
      patients suffer from dry eye symptoms.

PMID- 20799160
TI  - Genetic parameter estimates for buffalo milk yield, milk quality and mozzarella
      production and Bayesian inference analysis of their relationships.
AB  - Buffalo milk has excellent physical and chemical qualities as a consequence of
      the high percentage of constituents. This milk property is desirable for the
      dairy industry because it facilitates manufacture of mozzarella cheese. We
      estimated genetic parameters for milk yield, milk fat and protein and their
      effects on mozzarella cheese production using Bayesian inference. Using
      information from 4907 lactation records of buffaloes, genetic and non-genetic
      parameters were estimated for accumulated 305-day milk yield (MY), milk fat (%F)
      and protein (%P) percentages and mozzarella production per lactation (MP). The
      (co)variance components were obtained by Bayesian inference using a multiple
      trait model, which included as fixed effects contemporary group, milking number
      and buffalo age at calving as covariables (linear and quadratic), along with the
      additive genetic, permanent environmental and residual random effects. Mean a
      posteriori heritability distributions for MY, %F, %P, and MP were 0.25, 0.30,
      0.38, and 0.23, respectively. The genetic correlation estimates between MY with
      %P and %F were negative and moderate. Positive genetic correlation estimates
      varying from 0.19 (%P/MP) to 0.95 (MY/MP) were obtained among the traits. Milk
      yield, milk components, and mozzarella production in Murrah buffaloes have enough
      genetic variation for selection purposes. We conclude that selection to increase
      milk yield would be effective in improving mozzarella production.

PMID- 20799159
TI  - Guidelines for non-invasive and invasive mechanical ventilation for treatment of
      chronic respiratory failure. Published by the German Society for Pneumology
      (DGP).

PMID- 20799161
TI  - Genotyping in the Brazilian Criollo Horse Stud Book: resources and perspectives.
AB  - The goal of this research was to evaluate the ability of the genotyping
      information available in the Brazilian Criollo Horse Stud Book to describe the
      genetic variability of the breed and the exclusion probability determined in
      comparative tests. Altogether, two softwares were used in the analyses of the
      available genotypes: Cervus 3.0.3 and Genepop 4.0. Eight microsatellite markers
      totaled 109 alleles, with an average of 13.6 +/- 0.6 alleles per locus. Large
      differences between expected and observed heterozygosity were ubiquitous (0.821
      +/- 0.07 and 0.470 +/- 0.17, respectively). Although the estimated null allele
      frequency caused initial concern (0.284 +/- 0.199), it is likely that it was a
      reflection of the inbreeding coefficients found (0.432 +/- 0.184). All loci
      showed significant deviation from Hardy-Weinberg equilibrium, with heterozygote
      deficit (P < 0.0001) and genotypic linkage disequilibrium with at least one
      marker. The high polymorphic information content (0.798 +/- 0.088) could not
      warrant exclusion power for three loci (HMS7, HMS6 and HTG4) above 50% (0.491 +/-
      0.158). However, combined exclusion probability reached 99.61%, a level close to
      ideal. The results demonstrate the excellent performance of the markers assessed
      in describing the genetic status of the breed and suggest the considerable
      ability to establish parentage.

PMID- 20799162
TI  - Possible origins of B chromosomes in Rineloricaria pentamaculata (Loricariidae,
      Siluriformes) from the Parana River basin.
AB  - We made a cytogenetic study of Rineloricaria pentamaculata from the Taua Stream,
      in the Pirapo River sub-basin in Parana State, Brazil, focused on the occurrence
      and origins of the B chromosomes. The diploid number varied from 2n = 56 to 2n =
      59, due to the presence of 0 to 3 B microchromosomes of the acrocentric type,
      which were observed in 92.3% of the specimens (N = 12). These chromosomes were
      totally heterochromatic, with the C banding technique, and there were inter- and
      intraindividual numerical differences. Meiotic cells in metaphase I had 28
      bivalent chromosomes and 0 to 3 univalent chromosomes. We suggest that the B
      microchromosomes are centric fragments originated from chromosome rearrangements.

PMID- 20799163
TI  - CARMEN - Comparative Analysis and in silico Reconstruction of organism-specific
      MEtabolic Networks.
AB  - New sequencing technologies provide ultra-fast access to novel microbial genome
      data. For their interpretation, an efficient bioinformatics pipeline that
      facilitates in silico reconstruction of metabolic networks is highly desirable.
      The software tool CARMEN performs in silico reconstruction of metabolic networks
      to interpret genome data in a functional context. CARMEN supports the
      visualization of automatically derived metabolic networks based on pathway
      information from the KEGG database or from user-defined SBML templates; this
      software also enables comparative genomics. The reconstructed networks are stored
      in standardized SBML format. We demonstrated the functionality of CARMEN with a
      major application example focusing on the reconstruction of glycolysis and
      related metabolic reactions of Xanthomonas campestris pv. campestris B100. The
      curation of such pathways facilitates enhanced visualization of experimental
      results, simulations and comparative genomics. A second application of this
      software was performed on a set of corynebacteria to compare and to visualize
      their carbohydrate metabolism. In conclusion, using CARMEN, we developed highly
      automated data analysis software that rapidly converts sequence data into new
      knowledge, replacing the time-consuming manual reconstruction of metabolic
      networks. This tool is particularly useful for obtaining an overview of newly
      sequenced genomes and their metabolic blueprints and for comparative genome
      analysis. The generated pathways provide automated access to modeling and
      simulation tools that are compliant with the SBML standard. A user-friendly web
      interface of CARMEN is available at http://carmen.cebitec.uni-bielefeld.de.

PMID- 20799164
TI  - Phylogenetic relationships among Saccharum clones in Pakistan revealed by RAPD
      markers.
AB  - Forty sugarcane genotypes (clones), including elite lines, commercial cultivars
      of Saccharum officinarum and S. barberi clones, were fingerprinted with 30 RAPD
      markers, using a PCR-based marker assay. The genetic distance for RAPD data was
      determined according to Nei, and relationships between accessions were graphed in
      a dendrogram. Genetic distance values ranging from 16.2 to 86.3% were observed
      among the 40 sugarcane accessions. The lowest genetic distance was found between
      genotypes US-406 and US-186. These two genotypes differed from each other in only
      25 bands with 15 different primers. Genotypes Col-54 and CP-72-2086 were the
      second most similar group, with a genetic distance of 19.46%. The most dissimilar
      of all the accessions were CP-77-400 and US-133, with a genetic distance of
      86.3%. RAPD fingerprints help sugarcane breeders clarify the genetic pedigree of
      commercial sugarcane varieties and can be used to evaluate the efficiency of
      conventional breeding methods.

PMID- 20799165
TI  - A small supernumerary marker chromosome, derived from chromosome 22, possibly
      associated with repeated spontaneous abortions.
AB  - We report a phenotypically normal couple with repeated spontaneous abortions and
      without other clinical features. Clinical, hematological, biochemical, and
      endocrinological aspects of the couple did not reveal any abnormalities. The
      karyotype of the wife was normal (46,XX), while the husband was found to have an
      abnormal karyotype, 47,XY,+der(22)mat. The marker chromosome was familial and non
      satellite. Although the potential risk of small supernumerary marker chromosomes
      for spontaneous abortions cannot be defined precisely, marker chromosomes,
      together with methods used for ascertainment, are also factors to be considered
      when investigating infertility consequences. Furthermore, identification of the
      origin of a marker chromosome may provide additional information for patient
      karyotype-phenotype correlations. Further studies, such as molecular analyses to
      identify the breakpoint, are necessary for investigating phenotype-genotype
      correlations and assessment of genetic risks for small secondary chromosomes. The
      cause of repeated spontaneous abortions in this couple might be the presence of
      this marker chromosome in the husband. Consequently, we recommended genetic
      counseling before further pregnancies.

PMID- 20799166
TI  - Aortobifemoral embolism in an 18-year old patient following cisplatin and 5
      fluorouracil chemotherapy for nasopharyngeal carcinoma.
AB  - After cisplatin / 5-fluorouracil chemotherapy for nasopharyngeal carcinoma, an 18
      year female patient developed aortobifemoral embolism. Besides chemotherapy,
      additional risk factors for arterial thromboembolic events were smoking,
      contraceptive medication and adjuvant antiemetic treatment with dexamethasone.
      Thrombophilia screening was negative. Thromboembolic complications during or
      after cisplatin have been reported in a frequency of 17.6 % in lung cancer
      patients, and in 8.4 % of patients with germ cell tumors. The incidence of
      arterial thromboembolic events was 9.3 % and 1.7 %, respectively. The
      pathogenesis of cisplatin induced thromboembolism is thought to be caused by
      endothelial damage leading to endothelial cell dysfunction, increased von
      Willebrand factor plasma levels, and hypomagnesaemia.

PMID- 20799167
TI  - Functionalized nanomaterials for diagnosis and therapy of cancer.
AB  - Recent developments in nanotechnology have provided new tools for both cancer
      imaging and treatment. The functionalization of the nanocarrier based drugs using
      biological ligands allows increasing specificity of drug targeting enhancing
      efficacy and reducing side effects. In this paper some current nanocarrier based
      drugs are described and the principles for their functionalization in cancer
      treatment and imaging are reviewed.

PMID- 20799168
TI  - A room-temperature autonomically-healing PMMA bone cement: influence of
      composition on fatigue crack propagation rate.
AB  - PURPOSE: To test two hypotheses. First, autonomic healing is achievable in a
      commercially available poly (methyl methacrylate) bone cement brand that is
      widely used to anchor total joint replacements. Secondly, in this self-healing
      cement, the fatigue crack propagation (FCP) rate is critically dependent on the
      relative amount of the mass of the healing agent (endo-isomer of
      dicyclopentadiene (DCPD) embedded in poly (urea-formaldehyde) (PUF) microcapsules
      (diameter = 226 plusmn; 51 mu;m)) (MDM) to that of the catalyst (a first
      generation Grubbsrsquo; catalyst) (MGC). (Note that, in this work, the term,
      ldquo;autonomic healingrdquo; or ldquo;self healingrdquo;, refers to the ability
      of the material, after having been damaged during service, due to formation of
      cracks, for example, to restore its initial mechanical performance without the
      need for any external intervention). METHODS: The strategy that was developed by
      White et al. for room-temperature autonomic healing of a neat polymeric material
      was used. The DCPD-filled PUF microcapsules and the catalyst were blended with
      the cementrsquo;s powder in a mortar bowl using a polymeric spatula, and the
      blended powder mixture and the cementrsquo;s liquid monomer were mixed under a
      partial vacuum. FCP tests were performed on specimens of seven study groups: the
      control cement (CMWTM1), four sets having different values of MDM/MGC, one set in
      which only the DCPD-filled microcapsules were blended with the CMWTM1 powder, and
      one set in which only the Grubbsrsquo; catalyst was blended with the CMWTM1
      powder. RESULTS: An index of the self-healing achieved, as computed using the
      estimated FCP rates, was within the range reported in the literature for
      autonomically-healing neat polymeric materials. Furthermore, the variation of the
      estimated FCP rate with MDM/MGC suggests that changes in this rate is critically
      dependent on change of MDM/MGC. CONCLUSION: The results supported both of the
      study hypotheses.

PMID- 20799169
TI  - Meniscal shear stress for punching.
AB  - AIM: Experimental determination of the shear stress for punching meniscal tissue.
      METHODS: Meniscectomy (surgical treatment of a lesion of one of the menisci) is
      the most frequently performed arthroscopic procedure. The performance of a
      meniscectomy is not optimal with the currently available instruments. To design
      new instruments, the punching force of meniscal tissue is an important parameter.
      Quantitative data are unavailable. The meniscal punching process was simulated by
      pushing a rod through meniscal tissue at constant speed. Three punching rods were
      tested: a solid rod of Oslash; 3.00 mm, and two hollow tubes (Oslash; 3.00-2.60
      mm) with sharpened cutting edges of 0.15 mm and 0.125 mm thick, respectively.
      Nineteen menisci acquired from 10 human cadaveric knee joints were punched (30
      tests). The force and displacement were recorded from which the maximum shear
      stress was determined (average added with three times the standard deviation).
      RESULTS: The maximum shear stress for the solid rod was determined at 10.2 N/mm2.
      This rod required a significantly lower punch force in comparison with the hollow
      tube having a 0.15 mm cutting edge (plt;0.01). CONCLUSIONS: The maximum shear
      stress for punching can be applied to design instruments, and virtual reality
      training environments. This type of experiment is suitable to form a database
      with material properties of human tissue similar to databases for the
      manufacturing industry.

PMID- 20799170
TI  - The role of fibronectin in cell adhesion to spiral patterned TiO2 nanoparticles.
AB  - Spiral micropatterned surfaces of decreasing dimensions were produced by photo
      immobilizing a photo-reactive hyaluronan (Hyal) derivative on TiO2 nanoparticles.
      The microstructured surfaces were characterized by both scanning electron
      microscopy and atomic force microscopy analysis. The behavior, of both
      endothelial cells (HCAEC) and tumoral mouse fibroblasts (NIH3T3) on the patterned
      surfaces was evaluated. HCAEC adhered only to the TiO2 nanoparticles avoiding
      contact with the Hyal. NIH3T3 adhered to and completely covered the TiO2 spiral
      but prolonging the culture time, it also covered the external photo-immobilized
      Hyal surface. The role of fibronectin to mediate cell adhesion to the TiO2
      pattern surfaces was evaluated by experiments with blocked fibronectin membrane
      receptors on both HCAEC and NIH3T3. The results showed the absence of any
      adhering cells. Therefore, fibronectin seemed to be the only key protein in
      mediating cell adhesion to these TiO2 substrates.

PMID- 20799171
TI  - Thickness effects on maximum von-Mises stress of a cement mantle in total hip
      replacement - a finite element study.
AB  - AIM: The present study seeks to increase the life term of fully cemented total
      hip replacements by minimizing the stress values within the cement mantle.
      METHODS: Three-dimensional (3D) finite element analyses have been carried out to
      investigate the effects of varying cement thickness on the von-Mises stress of a
      cement mantle. The magnitude and location of maximum von-Mises stress within the
      cement mantle have been studied for both straight and tapered prosthetic stems.
      RESULTS: For prosthetic stems having lower radii sizes, the maximum stress zone
      is found in the upper region of the cement mantle whilst for stems with higher
      radii sizes the maximum stress zone is found in the lower region of the cement
      mantle. For the same cement thickness, straight stems are found to produce lower
      maximum stress values in the cement when compared to tapered stems. Finally, for
      the straight models with the same cement thickness, maximum stress values are
      found to decrease with increasing stem radius. CONCLUSIONS: It can be concluded
      that the maximum stress values in the cement mantle decrease with decreasing
      cement thickness.

PMID- 20799172
TI  - SEM evaluation of root canal dentin morphology after Ni-Ti instrumentation.
AB  - PURPOSE: The aim of this study was to compare, through scanning electron
      microscope (SEM), the ability of four Ni-Ti rotary instrument systems in shaping
      root canal walls and their ability in removing smear layer and dentin debris.
      METHODS: Forty-six extracted single-rooted human teeth were divided into four
      groups and prepared to size 35 (Alpha System, FlexMaster, MFile) or 30 (NRT
      files). Irrigation was carried out with NaOCl and EDTA. Three parameters were
      evaluated in the coronal, middle, and apical thirds of the root canals: smear
      layer morphology, pulpal-inorganic debris presence and surface profile
      morphology. Data were statistically analyzed using the Kruskal-Wallis test
      (ANOVA). RESULTS: None of the Ni-Ti rotary instrument systems resulted in being
      able to obtain constantly regular shaped surfaces in apical thirds, where smear
      layer, pulpal and inorganic debris were often present. CONCLUSIONS: NRT file
      specimens resulted in being relatively free from debris and smear layer and
      gained better results and scores at any canal level.

PMID- 20799173
TI  - The effect of surfactants, crosslinking agents and L-cysteine on the
      stabilization and mechanical properties of bovine pericardium.
AB  - AIM: Bovine pericardium (BP) is a collagenous tissue commonly used in
      cardiovascular applications. However, it suffers from thrombus formation and
      calcification, the latter generally being related to cell debris and the use of
      glutaraldehyde (GA). With this in mind, BP was decellularized, crosslinked and
      grafted with L-cysteine in order to improve its stabilization and mechanical
      properties. METHODS: BP was decellularized with ionic and non-ionic surfactants
      such as sodium dodecyl sulfate (SDS), cetyl trimethyl ammonium chloride (CTMA) or
      t-octyl phenoxy polyethoxy ethanol (Triton X-100). It was then crosslinked with 1
      (3-dimethyl amino propyl)-3-ethyl carbodiimide hydrochloride (EDAC) or GA.
      Finally, residual aldehyde groups on GA only or EDAC-GA crosslinked pericardium
      were left to react with L-cysteine (Cys). RESULTS: It was found that the
      treatment with GA led to a biomaterial with a lower amino-group content than the
      treatment with EDAC (15 vs. 50 micro;mol/g). The increase in denaturation
      temperature from 71.2 plusmn; 0.5 to 86.3 plusmn; 0.8 deg;C confirmed that GA was
      a more effective crosslinking agent than EDAC. In a similar manner, crosslinking
      with GA increased the percentage of deformation while decreasing their tensile
      strength. CONCLUSION: The amount of grafted Cys varied from 3 to 9 micro;mol/g
      thiol-groups and depended on the concentration of this amino acid and method of
      crosslinking, but did not modify its physicochemical and mechanical properties.

PMID- 20799174
TI  - Effect of light curing and dark reaction phases on the thermomechanical
      properties of a Bis-GMA based dental restorative material.
AB  - PURPOSE: The effects of light curing units (LCU) and energy doses on the chemical
      and physical properties of a dental composite were investigated. METHODS: The
      effects on the chemical and physical properties of a bisphenol A diglycidylether
      methacrylate (Bis-GMA) based dental restorative material were evaluated through
      photospectrometry, differential scanning calorimetry, and mechanical
      measurements. RESULTS: The light curing conditions associated with direct and
      indirect restorations were replicated in vitro using optical investigation
      techniques. A slight attenuation resulted independently of the LCU and a strong
      attenuation was measured for the cement luting a thick inlay, as well as for the
      deepest layer of a composite filling increment. Calorimetric measurements
      indicated that the curing degree is very sensitive to the light energy dose
      rather than to the LCU. Mechanical testing showed a transient phase during which
      properties increased. The delay of the composite in reaching adequate properties
      is strongly dependent on the energy dose. CONCLUSIONS: It is recommended that
      composites subject to unfavorable light curing conditions undergo a prolonged
      light curing process.

PMID- 20799175
TI  - Nanostructured surfaces for biomedical applications. Part I: nanotopography.
AB  - The natural cell environment provides a variety of chemical, topographical and
      mechanical stimuli that contribute in regulating cell behavior and function. If
      considerable effort has been traditionally dedicated to exploring the chemical
      side of cell regulation, it was more recently demonstrated that topographic cues
      might be equally important. Cell substratum interactions are particularly crucial
      in determining the reaction of cells to biomaterials, which was also shown to be
      strongly determined by topographical cues. A significant acceleration in
      investigating this aspect came from the availability of techniques for
      microstructured surfaces, and is now well known that cells can react to
      topographical features at their own scale (1-100 micron). Nevertheless, cells
      possess many nanoscaled features such as filopodia and a cytoskeleton, and the
      extracellular matrix (ECM) itself possess quite a few nanoscale details.
      Therefore, the capability of controlling the surface structure of materials in
      the nanoscale has offered the possibility of adding another level in the
      hierarchical understanding of cell/biomaterial interactions. Nanofabrication
      methods, mainly developed out of the semiconductor industries, are a
      technological driver for addressing the nanotopography related aspects of cell
      behavior. General concepts regarding some of the more widely utilized techniques
      that enable the achievement of ordered and well-defined nanoscale features for
      the investigation of cell reaction to topography are presented together with a
      few examples of the practical applications available in the literature.

PMID- 20799176
TI  - Perspectives for the tissue engineering of cartilage from a biological and
      biomaterial point of view.
AB  - Tissue engineering has become a fast growing interdisciplinary branch of research
      at the interface between life and engineering sciences with important clinical
      end-points. In this context the regeneration of articular cartilage represents an
      exciting challenge since hyaline cartilage has a limited capacity for self
      repair. Today the use of different scaffold materials combined with in vitro
      expanded chondrocytes and signalling molecules poses great hopes for an optimal
      treatment of articular cartilage defects. However, until today the optimal
      construct of scaffolds, cells and signalling molecules has not yet been found.
      Since repair and regeneration recapitulate in part ontogenetic processes, the
      present paper summarizes the regulative mechanisms of endochondral ossification
      in the growth plate of the long bones to identify possible new signalling
      molecules for the improvement of tissue engineering-based solutions in the
      treatment of cartilage defects. The growth plate represents a highly organized
      structure of chondrocytes and extracellular matrix components in distinguishable
      proliferation and differentiation stages. It is regulated by various paracrine
      and hormonal factors. In a second part we present actual trends in scaffold
      design based on synthetic polymers and natural polymers, stressing their
      potential use in the regeneration of cartilage defects from the point of view of
      bioactivity and biocompatibility. In conclusion, both new signalling molecules
      from basic research and innovative scaffold materials with variable physico
      chemical properties open up new and interesting perspectives for the research in
      optimized tissue engineeredbased therapeutic strategies to treat cartilage
      defects.

PMID- 20799177
TI  - In vitro cytotoxicology model of oligo-chitosan and n, o-carboxymethyl chitosan
      using primary normal human epidermal keratinocyte cultures.
AB  - Chitosan (beta-1, 4-D-glucosamine) is a deacetylated form of chitin with
      excellent biological properties in wound management. The natural properties of
      chitosan have the physical and chemical limitations to be widely used in
      biomedical fields. The improvement of the physical and chemical properties of
      chitosan with some additional chemicals will alter its biocompatibility.
      Therefore, the biological attribute of the modified chitosan must be evaluated.
      In this study, the cytotoxicity of oligo-chitosan (OC) and N, O- carboxymethyl
      chitosan (NO-CMC) derivatives (O-C 1%, O-C 5%, NO-CMC 1% and NO-CMC 5%) was
      evaluated using primary normal human epidermal keratinocyte (pNHEK) cultures as
      an in vitro toxicology model at standardized cell passages (fourth passages). 3
      [4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl tetrazolium bromide (MTT) was used as a
      cell viability assay. The O-C 1% is one of the most compatible chitosan
      derivatives because it steadily sustained >70% of viable cells until 72 hr post
      treatment. This was followed by O-C 5%, NO-CMC 5% and NO-CMC 1%. Therefore, oligo
      chitosan had the ideal properties of a biocompatible material compared to N, O-
      carboxymethyl-chitosan in this study.

PMID- 20799178
TI  - Amidated pectin based hydrogels: synthesis, characterization and
      cytocompatibility study.
AB  - The design and development of pectin-based hydrogels were attempted through the
      chemical modification of pectin with diethanolamine (DA). Diethanolamine modified
      pectin (DAMP) was synthesized by the chemical modification of pectin with varying
      concentrations of DA (1:1,1:2,1:3 and 1:4) at 5 oC in methanol. The modified
      product was used for the preparation of the hydrogel with glutaraldehyde (GA)
      reagent. The prepared hydrogels were characterized by Fourier transform infrared
      (FTIR) spectroscopy; organic elemental analysis, and X-ray diffraction (XRD), and
      swelling, hemocompatibility and cytocompatibility studies of the prepared
      hydrogels were also done. FTIR spectroscopy indicated the presence of primary and
      secondary amide absorption bands. The XRD pattern of the DAMP hydrogel clearly
      indicated that there was a considerable increase in crystallinity as compared to
      parent pectin. The degree of amidation (DA) and molar and mass reaction yields
      (Ym and Yn) was calculated based on the results of organic elemental analysis.
      Drug release studies from the hydrogel membranes were also evaluated in a Franz's
      diffusion cell. The hydrogels demonstrated good water holding properties and were
      found to be compatible with B-16 melanoma cells and human blood.

PMID- 20799179
TI  - Poly(methyl methacrylate) membranes with controlled porosity for advanced multi
      step drug elution.
AB  - Most of the systems developed for controlled drug delivery applications depend on
      membrane technology and their preparation parameters. For some applications, a
      dense membrane structure used in controlled-release systems can excessively
      prolong drug release due to the low permeability of the coating to the drug or to
      the low solubility of the drug in water. In these cases, to increase the drug
      delivery rate, asymmetric membranes can be prepared by a phase-inversion
      technique, allowing a different drug delivery approach with respect to dense
      membranes. In this study, porous poly(methyl methacrylate) membranes with
      different vacuum degrees were prepared through the phase-inversion process.
      Ternary homogeneous solutions, obtained by mixing polymer, tetrahydrofuran (THF)
      and water in the desired amounts, were precipitated by the evaporation of a
      solvent (THF) and a non-solvent (water) at a controlled temperature and
      ventilation. Membrane morphology, investigated by scanning electron microscopy,
      showed it to have a diffuse porosity with a regular arrangement and geometry of
      pores on the top surface. The porosity degree of the membranes, mainly relying on
      the starting polymer concentration, was also investigated by the use of the
      software Image-Pro Plus, indicating the presence of a relationship between
      porosity and permeability characteristics. Membranes, containing folic acid as a
      model drug, were tested for their transport characteristics and drug delivery
      both in diffusive and in convective- diffusive conditions. Transport and release
      parameters, as well as permeability and effective diffusivity, were found to be
      dependent on the porosity and vacuum degree, which could be controlled by varying
      the preparation conditions. Furthermore, these membranes showed high hydraulic
      permeability and rapid drug release, suggesting their use for applications where
      an intensive therapy in the first few days is required, followed by a constant
      and slow release for a longer time (two-step drug delivery).

PMID- 20799180
TI  - A new electro-mechanical bioreactor for soft tissue engineering.
AB  - By enabling the maintenance of controlled chemical and physical environmental
      conditions, bioreactors proved that electro-mechanical stimulation improves
      tissue development in vitro, especially in the case of tissues which are
      subjected to stimuli during embryogenesis and growth (i.e. skeletal and cardiac
      muscle tissue). However, most of the bioreactors developed in the last 20 yrs,
      designed to suit specific applications, lack versatility. With the aim to provide
      researchers with a yielding, versatile tool, we designed and realized in this
      study an electro-mechanical stimulator capable of dynamically culturing four
      biological constructs, delivering assignable stretching and electrical
      stimulation patterns. The device has been conceived to be easy to handle and
      customizable for different applications, while ensuring sterility along with
      stimuli delivery. The gripping equipment, modular and adaptable to scaffolds of
      different consistencies, is provided with dedicated tools for supporting sample
      insertion into the culture chamber performed under a laminar flow hood. As to
      performance, a wide range of electro-mechanical stimulation patterns and their
      relative occurrence can be accomplished, permitting the adjustment of the dynamic
      culture parameters both to the specific cell species and to the developmental
      phase of the cultured cells.

PMID- 20799181
TI  - Accelerated fatigue behavior and mechano-physical characterizations of in vitro
      physiological simulation of nitinol stents.
AB  - In this study, we have provided an experimental evaluation of the fatigue
      behavior of the nitinol (NiTi) endovascular device (peripheral stent). The
      accelerated fatigue tests were performed using arterial conditions, which
      mimicked actual physiological conditions. Natural, rubber latex-tubing materials
      were used to simulate human arteries. The equipment design and the test
      parameters used allowed for the simulation of a compliant artery and the
      application of circumferential forces to the device.The stent compliance values
      were good indicators for tracking the time evolution of fatigue behavior.
      Moreover, the analyses of changes on the surface morphology and on the chemical
      composition were used to establish a relationship between surface characteristics
      and peripheral stent response during 400 million cycles, which is equivalent to
      10 yrs of human life. In order to determine the influence of the accelerated
      fatigue, an evaluation of both mechanical and surface characteristics was carried
      out before and after testing using the following tests and methods, respectively:
      radial hoop testing (RH), scanning electron microscope analysis (SEM), auger
      electron spectroscopy (AES), atomic absorption spectroscopy (AAS), and X-ray
      photoelectron spectroscopy (XPS). Under these experimental conditions, the
      studies have shown that after 400 million cycles, the tested stents did not
      demonstrate any mechanical failure. Moreover, the surface did not undergo any
      changes in its chemical composition. However, we did observe an increase in
      roughness and signs of pitting corrosion.

PMID- 20799182
TI  - Electrically responsive smart hydrogels in drug delivery: a review.
AB  - Recently, much of the research activity has been focused on the development of
      stimuli-responsive hydrogels. Such hydrogels can show a response to the external
      or internal stimuli in the form of rapid changes in the physical nature of the
      polymeric network. This hydrogel property can be utilized for drug delivery
      applications. A literature search suggests that current research related to
      stimuli responsive drug delivery systems deals with temperature sensitive, pH
      sensitive, glucose sensitive and bio-molecule sensitive hydrogels. Electrically
      responsive hydrogels have also been recently developed in the form of gel
      matrices, implants and membranes for drug delivery. Control over the release of
      drugs such as quantity and timing, is essential to optimize drug therapy. Reports
      say that the electrically controlled in vitro and in vivo drug release studies
      have been carried out on polyelectrolyte hydrogels. A pulsatile pattern of drug
      release was achieved with the alternative application and removal of the
      electrical stimulus. This article gives an overview of the latest developments in
      the formulation of drug delivery systems using electrically responsive hydrogels.

PMID- 20799183
TI  - Effects of the surface pH on interfacial interactions of collagen-elastin matrix.
AB  - This study is aimed to elucidate the effects of surface pH of bioprosthetic heart
      valve (BHV) on their binding property to calcium and protein. It is hypothesized
      that the binding affinities of the BHV for calcium and protein are surface pH
      dependent. To test this hypothesis, collagen-elastin matrix (CEM) made of varying
      ratios of collagen and elastin were used as calcifiable matrices to simulate the
      calcium binding process of BHV. The calcium binding profiles of CEM, whose
      surface pHs were adjusted at 3.4, 5.0 or 7.4, were examined by either incubating
      CEM in the buffer solutions containing various calcium concentrations or
      implanting CEM in the rat subcutaneous model. The amounts of calcium and protein
      bound to CEM decreased as the surface pH of CEM decreased. The calcium level in
      the CEM (pH 7.4) was 2.32+/-0.8 as compared with 1.23+/-0.35 (microg/mg) in CEM
      (pH 3.4). The equilibrium dissociation constant (Kd) was in a reciprocal
      relationship with the surface pH. This study demonstrated that the affinity of
      CEM for calcium is surface pH dependent and provided basic information about the
      role of surface properties in BHV calcification.

PMID- 20799184
TI  - Porosity and mechanical properties relationship in PCL porous scaffolds.
AB  - Scaffold design plays a pivotal role in tissue engineering and regenerative
      medicine approaches for creating biological alternatives for implants. The
      crucial aspect in scaffold design consists of the development of highly porous
      scaffolds, with strict control of porosity features (porosity degree and pore
      sizes), continuing to provide an adequate mechanical response, mainly in
      compressive loading, both in vitro and in vivo conditions. A study was undertaken
      of three-dimensional (3D) porous scaffolds obtained from poly epsilon
      caprolactone solution through the phase inversion/salt leaching technique. In
      particular, the influence of structural porosity features on mechanical response
      was investigated to establish the correlation between structural parameters and
      compressive response. Scaffold porosity features can be controlled by changing
      the amount and size of the porogen agent used. Mechanical response in compression
      is consistent with porosity features: elastic modulus calculated in the toe
      region range (0-0.1 of total strain) shows an increase from 0.24-1.85 MPa
      coherently, with a reduction in pore volume fraction from 84.9 to 45.7%. Such
      behavior can be predicted by using analytical models for the determination of the
      elastic modulus of cellular solids based on the morphological assumption of cubic
      cell structure (cubic open cell (COC) and cubic closed cells (CCC)). Compressive
      behavior prediction offered by the proposed models is in agreement with the
      experimental results in the case of higher pore volume fractions according to the
      theoretical results of other investigators.

PMID- 20799185
TI  - A novel methodology to explore the viscoelasticity of spider major ampullate
      silk.
AB  - Even before material science was a recognized discipline, the amazing mechanical
      properties of spider silk were documented and became the object of much study. In
      addition to the exceptional material properties of spider silk and the reported
      low immunogenicity, its concatenated amino acid motif arrangement facilitates a
      distinct possibility of manipulating the silk to create a designer biomaterial
      for medical applications. Crystalline protein regions imbedded in a mobile
      protein matrix give it a distinct set of viscoelastic abilities. Consequently,
      elasticity cannot be simply quantified by only measuring extensibility. To
      understand how the sequence of the major ampullate proteins affects elasticity,
      the hysteresis of single fibers from two different species, Argiope aurantia and
      Nephila clavipes, were examined using cyclic loading and unloading. The yield
      point that discriminates a transition from elastic extension to a plastic
      extension was analyzed by examining three different properties: Young's modulus,
      energy recovery and slack in the fiber after recovery. Young's modulus remained
      relatively constant regardless of the cycle. However, the energy recovered
      decreased as the slack and cycle number increased. Large standard deviations
      masked any quantitative differences between species and substantiated the
      necessity of developing synthetic silk to harness the amazing mechanical
      properties of spider silk.

PMID- 20799186
TI  - Composite membranes modified with recognition-able nanobeads as potential
      adsorbers for purification of biological fluids.
AB  - Therapeutic approaches in the clinical field require advanced properties for
      delivery or recognition of clinical species. The molecular imprinting method
      allows selective cavities to be inserted into a polymeric material built
      ""around"" a stamp molecule (template) through polymerization or phase inversion.
      This study focuses on the application of both methods in the realization of
      polymeric membranes with selective recognition and adsorption properties.
      Imprinted polymethacrylic acid (PMAA) particles, exhibiting specific binding
      sites for cholesterol molecule (template), were realized via precipitation
      polymerization in the shape of nanobeads and loaded in the bulk or on the surface
      of methylmethacrylate-acrylic acid P(MMA-co-AA) membranes obtained by the non
      solvent induced phase separation (NIPS) technique. In this way, specific cavities
      were introduced into the membrane network to enhance and specialize uptake
      performances of the porous membranes taking advantage of the particle
      characteristics. Rebinding performances towards cholesterol in a physiological
      environment were tested showing very interesting results: the adsorption of
      cholesterol molecules from physiological solution was increased by using
      composite membrane-nanobead systems instead of control membranes (a quantitative
      increase of 14 mg of cholesterol per g of polymer matrix in respect of blank
      membrane was detected). The results obtained showed an improved performance of
      composite membranes, but also an unmodified behavior of loaded nanobeads (with
      respect to free ones) concerning the recognition capability in aqueous medium,
      which is the most difficult obstacle to overcome in molecular imprinting. The
      absolute rebinding capacity and the imprinting efficiency of membranes were in
      the range (and in some case higher) of other efficient systems, but the real
      improvement was that molecularly imprinted embranes showed an excellent
      recognition capacity in physiological medium instead of organic solvents.

PMID- 20799187
TI  - Mechanical properties of layered poly (ethylene glycol) gels.
AB  - Poly(ethylene glycol) (PEG) hydrogels have become a popular material for
      biomedical applications because of their versatility in use and design. As these
      gels are readily crosslinked under UV, microfabrication techniques have been
      investigated to manufacture complex three dimensional structures to better mimic
      the in vivo environment. This work investigated whether a layering technique to
      fabricate gels offered sufficient strength between the layers to perform
      similarly in mechanical testing to unlayered gels. Two mechanical tests were
      performed: tensile tests and peel tests. The tensile tests, which examined sample
      gels whose test sections were crosslinked for different durations, demonstrated
      no statistical differences in elastic modulus between sample and control gels. As
      expected, a statistical increase in the elastic modulus was found with increased
      PEG concentration. Comparison of the yield stress between samples and controls
      illustrated differences with total crosslinking duration, which may be due to the
      decreased molecular weight of the chains with decreased crosslinking time. In
      peel tests, no statistical differences of maximum peel force were found between
      samples and controls. However, an increase in the maximum peel force was found
      with increasing concentration of PEG. Overall, this study demonstrates that the
      layering process described for the PEG gels has minimal impact on the tested
      mechanical properties of the system. As mechanical properties are critical to the
      design of tissue engineered devices, these results demonstrate that this
      fabrication method may be appropriate for further study as a scaffold for complex
      cellular systems.

PMID- 20799189
TI  - Selected short papers from SIB 2007 - Italian National Congress.

PMID- 20799188
TI  - Biodegradable bioartificial materials made with chitosan and poly(vinyl alcohol).
      Part I: Physicochemical characterization.
AB  - Polymers have widespread applications in therapeutics, and their use can play
      important structural and functional roles in different disease conditions.
      Bioartificial biodegradable materials, to be used as biomaterials and, in
      particular, as localized drug carriers, were prepared mixing chitosan (CHI) and
      poly(vinyl alcohol) (PVA), then manufactured as films, and finally cross-linked
      with glutaraldehyde (GTA), both in the absence and in the presence of the edible
      plasticizer sorbitol (SOR). The materials were characterized by Fourier-transform
      infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), ther
      mogravimetric analysis (TGA), X-ray diffraction, scanning electron microscopy
      (SEM), and tensile test. The FTIR spectroscopy and the X-ray diffraction
      indicated that the presence of CHI lowers the crystallinity of PVA, and that the
      cross-linking with GTA does not modify the interactions between the two polymers,
      but only forms bridges between the different chains. In addition, the
      thermodynamic parameters for PVA, evaluated from the DSC measurements, confirmed
      that the PVA structure was less crystalline in the blends than in the pure state.
      The addition of SOR as a plasticizer to the CHI/PVA blends generally improved the
      characteristics of the films, making the cross-linked films less brittle, as
      confirmed by the SEM measurements and by the mechanical test. The TGA
      measurements confirmed the presence of chemical interactions between the
      polymers, as indicated by the DSC measurements. On the whole, the physicochemical
      properties of the blends showed the strong interactions existing between the
      component materials.

PMID- 20799190
TI  - Selected short papers from GIB-SIB 2006 - Italian National Congress.

PMID- 20799191
TI  - Advancements in carbohydrate bioactivity and implications for the surface
      modification of biomaterials.
AB  - This paper reviews recent advancements in the field of bioactive plant
      polysaccharides, and relevant implications forthe surface modification of medical
      devices. A number of complex plant polysaccharides exist, that display, for
      example, anti-inflammatoryactivity or specific effects on cultured mammalian
      cells. Advancements in the separation and purification of complex plant
      polysaccharides such as pectins, are paving the way for a conscious exploitation
      of some of these properties. Suitable immobilization methods and preliminary
      results on biological activity of surface-linked plant pectic polysaccharides are
      reviewed.

PMID- 20799192
TI  - MRI-based multiscale models for the hemodynamic and structural evaluation of
      surgically reconstructed aortic arches.
AB  - The surgical reconstruction of the aortic arch is necessary in pediatric patients
      suffering from different types of congenital heart malformations, in particular,
      coarctation of the aorta. Among the reconstruction techniques used in surgical
      practice end-to-end anastomosis (E/E), Gore-tex graft interposition (GGI) and
      Gore-tex patch graft aortoplasty (GPGA) are compared in this study with a control
      model, employing a computational fluid-structure-interaction scheme. This study
      analyzes the impact of introducing synthetic materials on aortic hemodynamics and
      wall mechanics. Three-dimensional (3D) geometries of a porcine aortic arch were
      derived from magnetic resonance imaging (MRI) images. Inlet conditions were
      derived from MRI velocimetry. A multiscale approach was used for the imposition
      of outlet conditions, wherein a lumped parameter net provided an active
      afterload. Evidence was found that ring-like repairs increased blood velocity,
      whereas GPGA limited it. Vortex presence was greater and longer lasting in GGI.
      The highest power losses corresponded to GPGA. GGI had an intermediate effect,
      while E/E dissipated only slightly more than the control case. Wall stresses peak
      in a longitudinal strip on the subject's left side of the vessel, particularly in
      the frontal area. There was a concentration of stress at the suture lines. All
      surgical techniques performed equally well in restoring physiological pressures.

PMID- 20799193
TI  - Structural change of biomimetic hydroxyapatite coatings due to heat treatment.
AB  - Biomimetic deposition of hydroxyapatite (HA) coatings on implants could be done
      for two reasons, one is to study their possible bioactivity, and one is to
      generate bioactive coatings on implants before implantation surgery to improve
      the osseointegration. Heat treatment of coated implants can be performed for
      several reasons, for example, to ensure coating sterility and to increase the
      adhesion. This paper describes the morphology and crystalline structure changes
      occurring due to the heat treatment of biomimetic HA coatings on rutile TiO2.
      Rutile TiO2 surfaces were produced on titanium (Ti) plates by heating at 800
      degrees C. Afterwards, these samples were immersed in a phosphate buffer saline
      solution for 7 days at 37 degrees C in order to deposit HA coatings on their
      surfaces. These HA coatings were then either untreated or heat treated at 600 or
      800 degrees C for 1 hr. The coatings microstructural changes were studied using X
      ray diffraction (XRD), scanning electron microscopy (SEM) and transmission
      electron microscopy (TEM). Cross-sectional TEM samples were produced using a
      sample preparation method based on focused ion beam microscopy (FIB). Rutile was
      found to be bioactive due to HA formation on the surface. The 600 degrees C heat
      treatment of the HA coating changed its morphology, increased its grain size and
      also increased the porosity. At 800 degrees C the coating was completely
      transformed to beta-TCP according to XRD. Sample preparation using FIB and TEM
      analysis proved to be a useful method for high-resolution analysis of biomimetic
      coatings in cross-section.

PMID- 20799194
TI  - Quantitative analysis of gait pattern and energy consumption in children with
      cerebral palsy.
AB  - The measurement of oxygen consumption during walking allows the quantification of
      gait expenditure, mainly in patients with musculoskeletal disabilities, as in
      cerebral palsy (CP). In this study, first, an experimental set up for the
      acquisition of energy consumption during gait analysis (GA) was proposed;
      secondly, some parameters of energy expenditure were analyzed to characterize
      pathological gait from an energetic point of view. Twenty CP children and 20
      healthy children were evaluated during two consecutive sessions (session 1: only
      GA was performed; session 2: K4b2 was used during GA acquisition). The results
      revealed that the experimental set up was comfortable for all subjects. The
      absence of any differences in GA values between the two sessions showed that the
      use of a device for energy acquisition does not modify gait pattern. Energy
      expenditure index and oxygen cost presented abnormal values in comparison with
      normality and they were significant to quantify energy expenditure in CP
      children.

PMID- 20799195
TI  - Mechanical properties of solvent-dehydrated bovine pericardium xeno graft for
      dura mater repair.
AB  - Collagen implants of dehydrated bovine pericardium have been developed as
      biodegradable materials for the surgical repair of cranial dura mater defects.
      However, the knowledge of the mechanical properties of the allograft is necessary
      to assess the reliability of the tissue reconstruction, since it is expected to
      withstand the functional loading in situ while the natural tissue heals. Tensile
      and stress-relaxation tests were performed on six rectangular samples of
      dehydrated bovine pericardium (DBP) graft (Tutogen Medical GmbH, Germany). In
      order to account for the anisotropic fiber architecture, the tests were run along
      two perpendicular directions of each graft, aligned to the sample edges. The
      stress-strain curves were non-linear, with fast stiffening at increasing strains.
      The stiffness in the transverse direction of the graft was only 1.5 times the one
      in the longitudinal direction, and for clinical purposes the xenograft can be
      considered as isotropic. The amount of stress relaxation was affected neither by
      the magnitude of the applied strain nor by the direction of stretching. The
      properties of the DBP were compared to the ones of native dura mater. Both the
      strength and the stiffness of cranial dura mater were well matched by the
      xenograft, but the graft material exhibited about twice the extensibility: the
      linear region of the stress-strain curve is attained at larger extension,
      although the slope of the curve in this region is similar to the native dura one.
      Pre-tensioning the graft in situ at surgery would reduce this slack strain; and
      therefore, improve compliance matching with the native tissue.

PMID- 20799196
TI  - Sol-gel synthesis, characterization and bioactivity of poly(ether-imide)/TiO2
      hybrid materials.
AB  - Novel organic-inorganic hybrid materials were synthesized by the sol-gel method
      from a multicomponent solution containing titanium butoxide, 6 weight % (wt%) or
      12 wt% poly(ether-imide) (PEI), water and chloroform. The structure of the
      interpenetrating network is realized by hydrogen bonds between the Ti-OH group (H
      donator) in the sol-gel intermediate species and the carboxylic group (H
      acceptor) in the repeating units of the polymer. By Fourier transform infrared
      (FTIR) analysis the presence of hydrogen bonds between organic-inorganic
      components of the hybrid materials were proved. The morphology of the hybrid
      materials was studied by scanning electron microscopy (SEM). The structure of a
      molecular level dispersion was disclosed by an atomic force microscope (AFM),
      pore size distribution and surface measurements. The AFM and SEM analyzes
      confirmed that the PEI/TiO2 samples can be considered homogenous
      organic/inorganic hybrid materials because in both the compositions studied the
      average domains were less than 400 nm in size. The bioactivity of the synthesized
      hybrid materials was demonstrated by the formation of a layer of hydroxyapatite
      on the surface of the PEI/TiO2 samples soaked in a fluid simulating the
      composition of human blood plasma (SBF), demonstrated by SEM and energy
      dispersive spectroscopy (EDS) microscopy.

PMID- 20799197
TI  - Two fluid-structure approaches for 3D simulation of St. Jude Medical bileaflet
      valve opening.
AB  - This paper deals with the three-dimensional (3D) numerical simulation of the
      opening transient for a bileaflet mechanical heart valve (St. Jude Medical
      Hemodynamic Plus, 27 mm characteristic size). The discussion concerns two
      different types of ""partitioned"" fluid-structure models, with weak and strong
      coupling. Both approaches are based on a moving deforming mesh method as
      implemented in the CFD commercial software Fluent (Fluent Inc., USA), and both
      yielded dynamically consistent results from a quantitative viewpoint. There is a
      slight improvement (peak relative difference <1%) of the numerical solution
      (angles vs. time) when using the strong instead of the weak coupling model. This
      is of utmost importance when the considerable reduction of the computational
      costs for the weak scheme (about 60% less) is taken into account. However, the
      strong coupling model provides a more consistent physical description of the
      interaction when looking at small-scale features like stress close to geometrical
      singularities. In the experiments, the differences both in terms of time-to-peak
      delay (15% of the opening time) and in terms of underestimation of the peak
      velocity (8%) seemed due to defects in the fluid inertia assessment, which
      depends on initial and boundary data.

PMID- 20799198
TI  - Cell-based biosensors: current trends of the development.
AB  - In the last decade, a number of laboratories have developed devices that combine
      electronic components with living cells, including neurons. These devices can be
      used as cell-based biosensors or labs-on-a-chip for testing of the tumor cell
      sensitivity to anti-cancer drugs, detection of toxins and chemical substances and
      pre-clinical evaluation of new drugs. Here we review briefly the existing types
      of the cell-based biosensors and the strategies employed to improve these complex
      devices. We argue that, for the neuron-based biosensors, introduction of
      structure in the connections of the synaptic network should significantly improve
      the utility of such devices.

PMID- 20799199
TI  - The effect of bone graft geometry on spinal fusion vertebral stresses.
AB  - Spinal fusion is a frequent surgical technique in which the success is uncertain
      due to post-operative changes in the biomechanics of the spine. Bone grafts are
      good candidates for disc and vertebra substitutes due to their similar bone
      properties and their good osteogenic properties. However, the effect of the
      anatomic harvest location of the bone graft on the load transfer is unknown. A
      physiologic three-dimensional (3D) finite element model of a lumbar spine was
      modified to model spinal fusion with a fixator and a bone graft. Bone grafts were
      taken either from the femur, the tibia, or from the fibula in a configuration of
      three or six fragments. The configurations were submitted to physiological
      loadings, and strain and stress distributions were calculated within the
      vertebrae, the fixator and the bone grafts. Quantitative differences were found
      from one type of bone graft to another. It was found that fibula bone grafts
      provided better stability by carrying a large part of the load. However, femoral
      and tibial bone grafts provided a more similar strain distribution within the
      vertebrae compared to the physiologic model. For tibial bone grafts, load
      transfer was found to be sensitive to the orientation used during the surgery.
      The use of a femoral bone graft to replace one vertebra and two intervertebral
      discs was found to give a better biomechanical function than using a tibial or
      fibula bone graft. This surgical technique is proposed to be beneficial in the
      case of severe spinal trauma providing good interface is obtained between the
      bone graft and the vertebrae.

PMID- 20799200
TI  - Effect of micrometer-scale metallic fillers on the mechanical and corrosion
      resistance properties of alternative materials for conservative dentistry.
AB  - In conservative dentistry, glass-ionomer cements (GICs) have been proposed as
      substitutes for composite resins. This is because the latter, although widely
      used over the last 10 yrs, exhibit inadequate physico-chemical properties.
      Although the performance of a typical commercial GIC is not yet optimal for
      restorative dentistry, the addition of metallic filler could improve this. In
      this study, a series of commercially available GICs were incorporated in trial
      dental amalgams, whose mechanical and calorimetric properties and morphologies,
      were examined. The metallic component of these amalgams comprised one of three
      metallic fillers, each including micrometer-scale metal particles of a different
      shape. The corrosion resistance of the amalgams, in fluids simulating the oral
      cavity environment, was also studied. The addition of metallic filler to GIC
      produced a general improvement in mechanical properties. Of particular note were
      increases in the elastic modulus, up to around sixfold, with the addition of
      Valiant metallic filler to the GIC Fuji II, and of the stress at break, up to
      around fourfold, for the New Gen metallic filler/GIC Fuji II amalgam. In these
      cases, the mechanical properties of dentine were studied. Micrographic
      observations showed a highly compact structure of the added GICs, thus reflecting
      a reduction in shrinkage. Calorimetric and dilatometric analyses further
      confirmed the suitability for applications in preservative dentistry. Finally,
      with respect to corrosion resistance, the effect of the introduction of the
      metallic filler was beneficial in samples with low porosity.

PMID- 20799201
TI  - Correlation of quantitative histopathological morphology and quantitative
      radiological analysis during aseptic loosening of hip endoprostheses.
AB  - OBJECTIVE: Aseptic hip prosthesis loosening is the most important long-term
      complication in total hip arthroplasty. Polyethylene (PE) wear is the dominant
      etiologic factor in aseptic loosening, which together with other factors induces
      mechanisms resulting in bone loss, and finally in implant loosening. The single
      shot radiograph analysis (EBRA, abbreviation for the German term ""Einzel-Bild
      Rontgenanalyse"") is a computerized method for early radiological prediction of
      aseptic loosening. In this study, EBRA parameters were correlated with
      histomorphological parameters of the periprosthetic membrane. METHODS:
      Periprosthetic membranes obtained from 19 patients during revision surgery of
      loosened ABG I-type total hip pros-theses were analyzed histologically and
      morphometrically. The pre-existing EBRA parameters, the thickness of the PE
      debris lay-er and the dimension of inclination and anteversion, were compared
      with the density of macrophages and giant cells. Addi-tionally, the
      semiquantitatively determined density of lymphocytes, plasma cells, giant cells
      and the size of the necrotic areas were correlated with the EBRA results.
      RESULTS: All periprosthetic membranes were classified as debris-induced type
      membranes. We found a positive correlation between the number of giant cells and
      the thickness of the PE debris layer. There was no significant correlation
      between the number of macrophages or all semiquantitative parameters and EBRA
      parameters. The number of giant cells decreased with implant duration.
      CONCLUSION: The morphometrically measured number of foreign body giant cells more
      closely reflects the results of the EBRA. The semiquantitative estimation of
      giant cell density could not substitute for the morphometrical analysis. The
      density of macrophages, lymphocytes, plasma cells and the size of necrotic areas
      did not correlate with the EBRA parameters, indicating that there is no
      correlation with aseptic loosening.

PMID- 20799202
TI  - Structural, mechanical and wear resistance assessment of UHMWPE orthopedic
      components.
AB  - The long-term survival of total joint prostheses is influenced by many factors.
      Among these factors, the most critical one is the presence of wear debris,
      particularly from the joint articulating surfaces. While ultra high molecular
      weight polyethylene (UHMWPE) has shown to be extremely promising in vitro and
      short-term clinical results, shelf-aged, oxidized components have been extremely
      unsuccessful clinically. Although shelf-aged components have been frequently
      tested in the laboratory, few studies have compared the properties of clinical
      retrievals to shelf-aged UHMWPE components. In this study, a thorough analysis
      method was developed and applied to both UHMWPE components retrieved at the time
      of revision, and non-implanted, shelf-aged UHMWPE components with the aim to
      understand better the significance of the in vivo factors on the material
      properties of the retrievals. The UHMWPE components were analyzed and
      characterized by visual observation of the surfaces, mechanical properties were
      assessed by small punch tests, wear resistance was analyzed by a multidirectional
      pin-on-disk test, and the oxidation level was detected by the Fourier transformed
      infrared (FT-IR) technique. The results indicated a strong correlation between
      the UHMWPE oxidation level, mechanical properties and wear resistance.

PMID- 20799204
TI  - Selected short papers from XV SIBOT National Congress.

PMID- 20799203
TI  - Optimization of cell seeding efficiencies on a three-dimensional gelatin scaffold
      for bone tissue engineering.
AB  - Bone tissue engineering techniques hold great potential for the treatment of
      clinical defects. However, there is much optimization needed before bone tissue
      engineering can be used therapeutically. This study evaluated various cell
      seeding methods onto a porous three-dimensional (3D) scaffold for bone tissue
      engineering optimization. MG63 human osteoblast-like cells were seeded onto a
      resorbable, porous gelatin sponge in different suspension volumes (50 microl and
      5 ml), and culture conditions, (static, shaken, rolled, or rotatory bioreactor).
      The DNA of the cells in the scaffold, the media and the containers were
      quantitated separately to determine the cell number and location after 3 days of
      culture. The samples were stained with calcein and viewed using confocal
      microscopy to determine cell viability and location. Placing a small cell
      suspension (50 microl) directly onto the scaffold produced a significantly higher
      proportion of cells adhered to the scaffold than a larger cell suspension (5 ml).
      In all conditions except the rotatory bioreactor, the percentage of cells
      remaining on the scaffold after 3 days in a small seeding volume (63 +/- 22%) was
      significantly higher than the larger seeding volume (36 +/- 25%). In the case of
      the rotatory bioreactor, the opposite appeared to be true (39 +/- 9% small volume
      and 72 +/- 14% larger volume). It was important to keep the seeding dynamics of
      the cultivated tissue engineered construct consistent throughout the experiments
      to ensure reproducibility. For this scaffold type, cells applied in a small
      volume and cultured on a plate shaker at 120 rpm (giving 81 +/- 14% of cells
      adhered to the scaffold) for 3 days is recommended.

PMID- 20799205
TI  - Gene therapy: The state of the art and future directions.
AB  - Gene therapy, because of its aim to eradicate the causes rather than the symptoms
      of diseases, is believed by many to be the therapy of the future. The problems of
      developing clinically viable gene therapeutic approaches and designing safe and
      efficient gene delivery reagents are inseparable: shortcomings in one are going
      to affect adversely the success of the other. It is generally accepted that the
      major impediment to the successful application of gene therapy for the treatment
      of a range of dis-eases is not a paucity of therapeutic genes, but the lack of
      efficient non-toxic gene delivery systems. Transfection vectors com-monly used in
      gene therapy are mainly of two types: viral and non-viral. Non-viral gene
      delivery is currently the subject of increasing attention because of its relative
      safety and its simplicity of use; however, its use is still far from being ideal
      due to its comparatively low efficiency. The purpose of this review is to give an
      overview of the current knowledge concerning the assembly of lipoplexes and the
      trafficking of lipoplexes into cells, as well as to underscore the advantages and
      disadvantages of lipidic gene carriers among non-viral gene delivery systems.

PMID- 20799206
TI  - A theoretical investigation of the supersaturation of basic calcium phosphate in
      serum of dialysis patients.
AB  - Extraosseous calcification in hemodialysis (HD) patients consists mainly of
      biological apatite, idealized as hydroxyapatite. Other suggested calcium
      phosphates are octacalcium phosphate (OCP) and brushite, both known to be
      hydroxyapatite precursors. Whatever the mechanisms of mineral deposition are,
      these mechanisms are always required to produce a supersaturated state, and that
      state can be calculated from the solubility product (SP) of the relevant mineral.
      Supersaturation in relation to serum ionized calcium [Ca 2+] and total inorganic
      serum phosphate (Pi) under normal and hyperphosphatemic conditions has been
      calculated. While supersaturation with respect to hydroxyapatite and OCP always
      exists, and supersaturation with respect to Ca5 (PO4)3 (HCO3) . 4H2O is just
      above the limit, supersaturation with respect to brushite solely occurs under hy
      perphosphatemic conditions. In order to avoid supersaturation with respect to
      brushite the maximum serum phosphate level al-lowed is 1.9 mmol/L (5.8 mg/dl) and
      the calcium-phosphate product (Ca x P) 4.5 (mmol/L)2 (56 (mg/dl))2 .

PMID- 20799207
TI  - Concentration and M/G ratio influence the physiochemical and mechanical
      properties of alginate constructs for tissue engineering.
AB  - The diffusion and mechanical properties of calcium alginate gels were determined
      using constructs of different alginate concentrations and guluronic acid
      contents. It was found that the diffusion of small molecules such as sulphate,
      glucose and thymidine was not impeded by any of the alginates tested at
      concentrations of 1% and 3% (w/v). By contrast, the diffusion of large molecules,
      including insulin like growth factor-1 (IGF-1), human growth hormone and bovine
      serum albumin was impeded by alginate. This effect was enhanced with increasing
      alginate concentration, but was less evident for alginates with increased
      guluronic acid content. These findings have significant implications in tissue
      engineering where cells such as chondrocytes depend on the supply of factors such
      as IGF-1 to remain viable. An increase in both alginate concentration and
      guluronic acid content also increased the compressive properties, as determined
      by both tangent and equilibrium modulus, of alginate constructs. Although the 3%
      alginate constructs exhibited enhanced stiffness compared to some reported
      cartilage substitute biomaterials, such as PGA, their absolute values were still
      appreciably less stiff than articular cartilage.

PMID- 20799208
TI  - Cross-linked ionomeric materials from poly(styrene-alt-maleic anhydride) and
      poly(ethylene glycol) for biomedical applications: a preliminary investigation.
AB  - Two ionomeric materials, cross-linked through the formation of polyoxyethylene
      bridges, were synthesized by the reaction of poly(styrene-alt-maleic anhydride)
      (PSMA) with poly(ethylene glycol) (PEG), carried out in the absence of external
      catalysts. The reaction was carried out at room temperature, both in bulk with
      excess glycol, and in acetone solution with a 20:1 ratio of anhydride rings to
      hydroxyl groups. The materials were characterized by scanning electron microscopy
      (SEM), total reflection Fourier transform infrared spectroscopy (FTIR),
      thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The
      SEM showed a quite uniform porous structure for the material synthesized in bulk,
      and two distinct phases for that synthesized in acetone solution, a sponge-like
      structure and a denser one. The FTIR spectra showed that the first material
      underwent the cross-linking reaction to a greater extent than the second one.
      Both TGA and DSC confirmed the formation of cross-linked structures. Such tri
      dimensional networks, owing to the presence of the carboxyl groups, could easily
      entrap either cationic drugs, in view of a possible controlled release, or
      poisonous metal cations, when they must be removed from blood. The second use can
      be made easier by the hemocompatibility, ascertained in preceding studies on
      other materials, synthesized by the reaction between maleic anhydride copolymers
      and hydroxyl-containing macromolecules. Another possible use is the production of
      ion exchanging gels, as fillers for both ion exchange and liquid chromatography
      columns, which could be easily regenerated.

PMID- 20799209
TI  - Bioactive porous scaffolds for tissue engineering applications: investigation on
      the degradation process by Raman spectroscopy and scanning electron microscopy.
AB  - Bioactive glasses in the Na2 O-K2 O-MgO-CaO-B2 O3 -P2 O5 -SiO2 system
      characterized by an unusually large working range were used for the production of
      fiber porous scaffolds. In vitro tests were carried out by immersing the
      scaffolds in simulated body fluid (SBF) solution; soaking time and glass
      composition effects on the degradation of the material are the principal subject
      of this investigation. Raman spectroscopy and scanning electron microscopy (SEM)
      were used as the main investigative methods. The study demonstrates the
      importance of the network modifiers and, in particular, of the amount of alkaline
      and al-kaline earths in the different stages of the material degradation and in
      the development of the hydroxyl-carbonate-apatite (HCA) layer.

PMID- 20799210
TI  - Multibody modeling of the cervical spine in the simulation of flexion-extension
      after disc arthroplasty.
AB  - This paper presents a three-dimensional (3D) multibody model of the cervical
      spine implanted with an artificial disc. The model was used to predict prosthesis
      placement influence on the resulting cervical kinematics in a series of patients.
      The vertebral tract modeled was the C2-C7, and the vertebral geometries were
      reconstructed from computed tomography (CT) images. The model was used to
      simulate the flexion-extension motion of the cervical spine in 10 patients
      implanted with the Prestige commercial disc prosthesis at a single level. For
      each patient, a geometrical model of the prosthesis was scaled and included in
      the multibody model to match the size and positioning of the actual prosthesis,
      as assessed on post-operative radiographs. Simulations of complete flexion
      extension were carried out for each patient, and the main parameters relevant to
      the motion of the vertebral bodies were calculated and compared to data measured
      from dynamic post-operative radiographs. At the implanted level, the simulated
      ranges of motion generally agreed with the measured ones, with an average
      deviation <2 degrees. In addition, the simulated relative angles between
      vertebral bodies agreed with the measured ones, with minor average differ-ences
      of 1.2, 1.8 and 2.1 degrees in full flexion, neutral alignment and full
      extension, respectively. The cervical kinematics after prosthesis placement was
      influenced both by the design of the artificial joint and by surgical
      positioning. Therefore, the model presented can be used both to support pre
      operative planning for disc arthroplasty and in the optimization of new
      prostheses design.

PMID- 20799211
TI  - Surface characterization of Streptococcus mutans biofilms grown on polyethylene
      and beta-titanium.
AB  - In this study, we considered the biofilms as a surface, characterizing them using
      instruments for surface analyses, environmental microscopy, IR-spectroscopy (ATR
      mode) and goniometry of the contact angle. The bacteria that formed the biofilms
      were grown on two different supports: beta-titanium alloy (beta-Ti) and
      polyethylene (PE). Environmental microscopy allowed the observation of biofilms
      in situ and in their hydrated state. On the metallic support, the biofilm quickly
      adhered and formed a dense structure with micro-colonies, but on the PE a thinner
      biofilm layer was observed covering a large surface area of the support. IR
      spectroscopy is another effective method to detect the biofilm quickly and in
      situ, without pre-treating the sur-face. Nevertheless, problems with the
      overlapping of the characteristic bands on the spectra are frequent between the
      biofilm and PE. Finally, we compared the surface energy (SE) of the supports
      before and after biofilm formation. Our results indicate that the SE of the
      supports depends on the sterilization method, and that the SE of the biofilms
      varies depending on the support and the sterilization method. The biofilm on the
      beta-Ti had the highest SE, and as mentioned above, microscopic images showed a
      higher roughness on its surface.

PMID- 20799212
TI  - Biopolyesters from microorganisms: Biochemical basis of microbial synthesis,
      properties and applications.
AB  - Biopolyester produced by microorganisms has many useful properties for commercial
      and environmental applications. Poly(3-hydroxyalkonates) [poly(HA)s] and poly (a 
      malate) are among the best known biopolyesters produced by microor-ganisms.
      Poly(HA)s having a wide variety of repeating units can be produced by bacteria
      and they all posses very high biodegradability and biocompatibility. Poly (a 
      malate) is especially of interest for biomedical applications including drug
      delivery systems. During the last 20 yrs a large volume of research work has
      focused on the physiology, biochemistry and applications of poly(HA)s. In this
      review, the biochemical basis of bacterial production, the biodegradation
      properties and applications of poly(HA)s are considered.

PMID- 20799213
TI  - Basic structural parameters for the design of composite structures as ligament
      augmentation devices.
AB  - Composite structures are designed to mimic the morphology and mechanical
      properties of natural ligaments. Filament winding technology has been implemented
      in order to obtain a composite material based on a polyurethane matrix
      (HydroThaneTM ), reinforced with degradable and non-degradable fibers. The
      mechanical properties of the matrix and fiber have been analysed to define the
      optimal type, volume ratio and winding angle of the reinforcement. The typical J
      shaped stress-strain curve, displayed by natural tendons and ligaments, is
      reproduced. The mechanical behaviour of HydroThaneTM reinforced with
      poly(ethylene terephthalate) (PET) fibers were modified by varying the winding
      angle of the fibers. Fibers comprising poly(l-lactic acid) (PLLA), poly(glycolic
      acid) (PGA) and PET, individually and in combination, were considered as
      candidate materials for the reinforcement of a composite ligament augmentation
      device (LAD). Mechanical and degradation studies demonstrated that, by combining
      different types of fiber, at a fixed volume fraction and winding angle (20
      degrees ), it is possible to optimize mechanical properties and degradation
      kinetics of the device.

PMID- 20799214
TI  - Release of proteinic and non-proteinic compounds from novel ionizable hydrogels:
      Effect of pH on swelling and drug delivery behavior.
AB  - Ionizable hydrogels were prepared from new copolymers, poly(vinylalcohol-co
      acrylic acid) indicated as P(VA-co-AA), by freezing-thawing processes. These
      materials are designed as potential controlled delivery devices with specific
      properties to respond to chemical environment stimuli. The swelling behavior of
      the P(VA-co-AA) hydrogels was evaluated in response to pH changes in release
      medium demonstrating a strong dependence with the environmental pH. The release
      of theophylline (THO) and bovine serum albumin (BSA) incorporated into the
      hydrogels before freezing-thawing cycles were examined by varying the pH. The
      release curves of the two different solutes showed a very similar trend depending
      on the hydrogel porosity and the medium pH. The dependence of THO and BSA release
      on their size and ionic nature was detected.

PMID- 20799215
TI  - Characterization of prepared corn starch-based hydrogel membranes.
AB  - The design and development of novel hydrogel membranes prepared by crosslinking
      polyvinyl alcohol with heat-treated cornstarch (CS) and CS suspensions was
      attempted. Degradation studies of the hydrogel membranes were conducted using a 
      amylase. The mechanical property of the hydrogel membranes was characterized by
      tensile tests. The swelling behavior of the membranes was also evaluated. Methyl
      tetrazolium assay of the membranes was performed using mice splenocytes and the
      L929 cell line to establish cytocompatibility. The membranes had sufficient
      strength and water holding capacity. The membrane was found to be biocompatible
      with L929 fibroblast cells and mice splenocytes.

PMID- 20799216
TI  - Biomechanical effects of prosthesis neck geometries to contrast limb lengthening
      after hip replacement.
AB  - Hip prostheses should meet the anatomical and physiological characteristics of
      patients; this is the rationale for designing modular implants of different
      sizes. To optimize implant geometry, it is necessary to consider, not only the
      prosthesis component design, but also the final configuration of the implanted
      leg. This means the necessity to consider the specific morphological and
      functional condition of ""that"" patient and not only of ""that"" hip to restore,
      at best, limb functions. Variations in the length of the implanted limb are
      frequent; therefore, the variations in the three geometrical features of the hip
      prosthesis neck, which can affect the restoration of the anatomical symmetry of
      the limbs, were investigated: (i) neck lengths (Ln ), between 50.5 and 64.5 mm;
      (ii) cervico-diaphyseal (CD) angle ( a ), between 135 and 125 degrees and; (iii)
      anteversion (AV) angle ( a ), between 0 and 15 degrees . Adopting a three
      dimensional (3D) simplified biomechanical model, the resultant load acting on the
      hip was estimated for each different design solution; corresponding stress
      distributions and contact pressures at the interface between the prosthesis head
      and the ultra high molecular weight polyethylene (UHMWPE) layer were evaluated by
      3D finite element (FE) analyses and using the Strozzi approach. The following
      values have been assumed as physiological values: a = a p = 125 degrees , a = a p
      = 15 degrees and Ln = 57 mm; it was found that to contrast limb lengthening, if
      the CD angle varies from 135-125 degrees (with neck length Ln = 64.5 mm and AV =
      0 degrees ), the joint resultant load decreases by 8.8% (7.2% if AV = 15 degrees
      ); the contact pressure de-creases by 5.8%, (5% if AV = 15 degrees ); the bending
      moment in the stem neck increases by 10.9% (13.8% if AV = 15 degrees ) and the
      torque increases by 1% (12.8% if AV = 15 degrees ).

PMID- 20799217
TI  - Selected short papers from SIB-GIB 2005 Italian National Congress.

PMID- 20799218
TI  - Factors affecting bone response around loaded titanium dental implants: A
      literature review.
AB  - This paper was designed as a review of the knowledge concerning bone adaptation
      around dental implants. Current literature concerning the biomechanics of bone
      and titanium dental implants as a main focus and pertinent to key aspects of the
      review was taken into consideration. Implant stiffness, design and surface were
      considered as factors affecting bone response to loaded dental implants. The
      emerging data allows the conclusion that implant design influences force
      transmission to periimplant bone, but seems to have poor power in preventing time
      related marginal bone crest resorption. Mechanical stimulation such as prosthetic
      stress-dependent strains, affects bone tissue adaptation. Therefore, it is
      crucial to have high biomechanical control on implants to preserve implant
      ankilosis and to promote periimplant bone deposition.

PMID- 20799219
TI  - The wear of two orthopaedic biopolymers against each other.
AB  - The potential for all-polymer prostheses has not been widely investigated. It
      might be expected that the wear of such biomaterial combinations would be
      excessive, but an in vivo study of all polymer knee prostheses reported that
      there were no failures due to wear, even after ten years of clinical use. This
      design of knee prosthesis used polyacetal and ultra high molecular weight
      polyethylene (UHMWPE) as the biopolymers. Similarly, an earlier in vitro study of
      polyacetal and UHMWPE hip prostheses indicated lower wear than for a cobalt
      chrome and UHMWPE combination. Therefore this study set out to test the poly
      acetal and UHMWPE combination in a wear screening rig which had previously been
      validated against clinical data for artificial hip joints. Two different motion
      conditions were applied to the test samples and each biopolymer was tested as
      both pin and plate. Interestingly it was found that, whatever the contribution
      from pin or plate, the total mean wear factors were 1.5 10 -6 mm 3/Nm under
      reciprocation-only, and 4.1 10 -6 mm 3 /Nm under multi-directional motion. These
      wear factors were greater than those found when a conventional metal-on-UHMWPE
      couple was tested under the same loading, motion and lu-bricant conditions. A
      comparison was also undertaken with the wear of other orthopaedic biopolymer
      combinations, namely cross-linked polyethylene (XLPE) against itself, and UHMWPE
      against itself. The XLPE pairing showed somewhat lower wear than the polyacetal
      and UHMWPE couple, while the UHMWPE pairing showed the highest wear of all,
      approximately an or-der of magnitude greater than the polyacetal and UHMWPE
      combination.

PMID- 20799220
TI  - Aortic tissue properties in porcine models: A comparison of ex vivo mechanical
      test results after simulated aortic arch reconstructions.
AB  - Surgical interventions on the arterial wall can produce modifications to its
      tissue characteristics, and the addition of synthetic materials of different
      types can have implications on hemodynamics and blood vessel wall behavior. This
      work studies the midterm effects of end-to-end anastomosis (E/E), Gore-tex graft
      interposition (GGI) and Gore-tex patch graft aortoplasty (GPGA) in aortic arch
      reconstruction. The study comprised of two groups of healthy Danish sows. The
      sows in the first group (short term (ST)) weighed about 40 kg, underwent a
      surgical operation and were sacrificed on the same day. The sows in the second
      group (midterm (MT)) weighed 5-10 kg, underwent a surgical operation and were
      then allowed to grow to a weight of about 30-40 kg, before being sacrificed. One
      sow in each group was scheduled for E/E and one sow for GGI. One sow in ST and
      two sows in MT received GPGA. The overall average wall thickness was 1.93 mm.
      Relaxation constant values were significantly higher for ST (5.221 +/- 1.832 sec)
      than for MT (2.184 +/- 1.216 sec). GPGA showed a greater impact on relaxation
      than other procedures, enhancing the viscous character. The working-point Young's
      modulus (Epw ) was not significantly different in ST and MT. Circumferential
      samples had different Epw (0.419 +/- 0.77 MPa) from longitudinal samples (0.902
      +/- 0.378 MPa). There also appeared to be a significant difference between
      samples cut longitudinally on the left and the right sides of the wall. The
      overall average Epw value was 0.6609 +/- 0.3641 MPa.

PMID- 20799221
TI  - Intramedullary nails vs osteosynthesis plates for femoral fracture stabilization:
      A finite element analysis.
AB  - In diaphyseal femoral fractures, an accurate quantification of the biomechanical
      differences between implants can help the surgeon make his choice. This study
      uses the finite element (FE) method to characterize the differences between
      intramedullary nails and osteosynthesis plates at different stages of femoral
      fracture healing, and assesses how these differences are affected by the size and
      consolidation of the fracture. Simulations were performed using a femur model
      with a 1 and 3 mm diaphyseal fracture at two stages of consolidation. The
      fracture was stabilized with an osteosynthesis plate or an intramedullary nail
      made of stainless steel (SS), titanium (Ti) or a composite material. The Ti
      implants bore lower von Mises stresses ( o vM ) than the SS implants, and o vM in
      the implants decreased with fracture consolidation. Nails tended to bear higher
      stresses than plates, though these differences were reduced in unstable
      fractures. This change in trend proves that fixation choice is critical for weak
      fractures. Both the dilatational stress o dil and the octahedral shear strain a
      oct of the fractures varied significantly with the type of fracture and fixation
      device. In accordance with the literature, our results suggest that plates induce
      fracture healing through intramembranous ossification without fracture callus
      formation. Nails, on the other hand, induce endochondral ossification with
      fibrous tissue formation. The composite implants have mechanical limitations, but
      increasing their yield stress could overcome these drawbacks.

PMID- 20799222
TI  - Titanium implants with two different surfaces: Histomorphologic and
      histomorphometric evaluation in rabbit tibia.
AB  - This study aimed to compare two different implant surface treatments of the
      implant system Bi-Implant (Plan 1 Health): one surface sandblasted with
      hydroxyapatite (HA) (Osseogrip(R)) and one machined surface. Histomorphologic and
      histomorphometric evaluations of the bone healing at the interface between a
      titanium implant and bone were performed using a light microscopic technique.
      Twenty-four commercially pure titanium implants with a smooth surface and 24
      implants with a sandblasted surface were inserted in the tibias of 12 rabbits.
      The 12 rabbits were divided into three groups, each consisting of four animals,
      were sacrificed at 4 weeks (I group), 8 weeks (II group) and 12 weeks (III group)
      after the insertion of the bio-material. The results emphasized that in the
      sections examined with the light microscope, the bone was in intimate contact
      with the implant surface and the bone surrounding the implants was mostly
      lamellar. After 4 weeks, mature bone tightly surround-ing some areas of the
      implant perimeter was observed. The implant with the Osseogrip(R) surface showed
      an average percentage of bone-implant contact (%BIC) equal to 33%, while the one
      with the machined surface showed a %BIC equal to 17%. After 8 weeks, a
      progressive increase in mineralized bone surrounding the implant surface was
      detected, making the results of the machined surface superposable to the
      Osseogrip(R) surface results (48 and 44%). After 12 weeks, the implants with the
      machined surface exhibited close contact with the bone tissue corresponding to
      62% of their perimeter, while for the implants with the Os-seogrip(R) surface the
      surface contact was 67% of the implant surface. The morphometric evaluation of
      %BIC at the three time points evidenced an increase in bone-titanium contact over
      time on both machined and Osseogrip(R) surfaces. Moreover, implants with rough
      surfaces demonstrated better behavior than the implants with the machined surface
      when taking into account the earlier osteointegration (4 weeks) of the peri
      implantar tissues.

PMID- 20799223
TI  - Study of non stationary mode flow of an abdominal aortic aneurysm.
AB  - INTRODUCTION: Abdominal aortic aneurysm rupture is 95% lethal. Numerical
      simulation of Navier-Stokes equations allows seeing complex flow phenomenon in
      laminar state. METHOD: In this study, we work on a model using the finite element
      method with an actual 3D geometry. This geometry is from a point cloud obtained
      by a tomodensitometry scan of a typical patient. We consider rigid wall,
      homogeneous and Newtonian fluid. We impose four pulsative waveforms as entrance
      condition: two rest waveforms, two exercise waveforms. The four aver-age Reynolds
      numbers are 353 and 363 for the rest waveforms and 1058 and 1388 for the exercise
      waveforms. For the systolic peaks, the Reynolds numbers are 1639 and 1917 for the
      rest waveforms and 2800 and 2497 for the exercise waveforms. RESULTS: RESULTS
      show that during the systolic acceleration, vortices issued from the previous
      pulsation are pushed out and the flow reattached on the wall. During the systolic
      deceleration, a main vortex appears in the upper part of the aneurysm; it grows
      and moves to the center. During the diastole, the vortex sustains itself until
      the next pulsation for the exercise conditions. For the rest conditions, imposed
      oscillations during the diastole lead to secondary vortices. Pressure stays
      relatively constant in the aneurysm following the entrance conditions.
      DISCUSSION: These results on the flow and pressure repartition agreed with those
      found in the literature (1-6) validating in a first time our model. The next step
      of the study is the wall shear stress data exploitation.

PMID- 20799224
TI  - Mechanical properties of breast periprosthetic capsules and the correlation to
      capsule contracture.
AB  - Contracture of the fibrous connective capsules that form around breast implants
      is the most frequent complication for silicone mammary prostheses. Capsule
      contraction is thought to be associated with the alteration in the mechanical
      properties of the tissue, but to date such a correlation has not been quantified.
      This study aimed to develop an experimental protocol to investigate the
      mechanical properties of the periprosthetic tissue and their dependence on the
      severity of capsular ontracture. Capsule samples were harvested from donors
      undergoing surgical correction or re-implantation of breast prostheses; strip
      spec-imens were cut along both the meridian and circumferential directions of the
      capsular dome. The experimental protocol consisted of mechanical preconditioning,
      stress relaxation tests and tensile tests to rupture. The capsular tissue
      exhibited non-linear stress-strain relationships and stress relaxation behavior;
      nevertheless, both the elastic and the relaxation properties did not depend on
      the loading direction. In spite of the small number of samples included, to date,
      in the experimentation, some pre-liminary conclusions can be drawn: the stiffness
      and the strength of the tissue increases with the contracture severity; the re
      laxation seems unaffected by the contracture degree. Some assumptions concerning
      the modifications in periprosthetic tissue composition following contracture are
      also drawn.

PMID- 20799225
TI  - Porous hydroxyapatite ceramics for tissue engineering.
AB  - We have determined the biocompatibility of high porosity (92%) sintered
      hydroxyapatite (HA) foams prepared using a novel ceramic foaming system. The
      ability of human osteoblast-like cells to grow within the HA foam was
      investigated in vitro using human osteosarcoma cells seeded directly on the
      ceramic surfaces to determine the bioactivity. Scanning electron microscopy
      showed evidence of attachment of numerous cells to the surface. Significant
      proliferation was observed and the pattern was comparable to that of the tissue
      culture control, Thermanox TM . There was an increase in cell proliferation and
      retention of phenotype for the period studied. This hydroxyapaptite foam which
      has the advantage of being easily fashioned by surgeons, shows potential as a
      bone substitute scaffold for tissue engineering and future development for
      clinical application.

PMID- 20799226
TI  - Tissue heart valve mineralization: Review of calcification mechanisms and
      strategies for prevention.
AB  - Attempts to replace diseased human valves with prostheses began more than 30 yrs
      ago. Heart valve prostheses can be broadly classified into mechanical prostheses
      (made out of non-biological materials) and bioprostheses made out of biological
      tissue. Biological valves are made from animal tissue bovine pericardium and
      porcine valves. The use of these tissues became commercially available after the
      introduction of the glutaraldehyde (GA) fixation technique. GA reacts with tissue
      proteins to form inter- and intramolecular crosslinks, resulting in improved
      durability. The advantage of bioprostheses compared with mechanical valves is the
      freedom from thromboembolism; and therefore, the avoidance of long-term
      anticoagulation therapy. These prostheses are preferable in elderly people and in
      patients who do not tolerate anticoagulants. However, tissular calcification and
      primary tissue failure (caused by the mechanical stress) are the main unresolved
      problems. The causes of calcification are numerous and, to date, a satisfactory
      solution to this question has not been found, although chemical treatments with
      metal cations, diphosphonates and treatments eliminating phospholipids have
      proved to mitigate calcification. In addition, alterna-tive approaches to GA
      chemical treatment fixation are being proposed to provide the tissue with greater
      resistance to this process. Studies are under way using polyepoxy compounds,
      derivates of amino oleic acid (AOA), agents such as diphenylphosphorylazide,
      carbodiimide, amino acids etc. Further improvements in fixation techniques, as
      well as in bioprosthesis design (stentless valves) are being made to improve the
      durability and functional characteristics of bioprosthetic heart valves. The
      development of a biomaterial capable of withstanding calcification and mechanical
      stress, while being as durable as mechanical prostheses, would convert the
      bioprostheses into the replacement of choice by eliminating the need for
      anticoagulation therapy.

PMID- 20799227
TI  - Designing porous bioartificial membranes for clinical use with desired
      morphological and transport properties by phase inversion control.
AB  - Bioartificial membranes of synthetic (poly(ethylene-co-vinyl alcohol) - EVAL,
      Clarene (R) ) and biological (dextran) polymers with different compositions were
      prepared through the phase inversion process. Dimethyl sulfoxide (DMSO) solutions
      of EVAL and dextran were mixed under stirring in the desired proportions and
      coagulated in water or DMSO (solvent)/water (non-solvent) mixture. Membrane
      morphologies were shown to be dependent on the synthetic and biological polymer
      contents and on the coagulation medium composition. Component release during
      solid membrane formation was evaluated by a UV method and the final composition
      of the bioartificial membranes established, confirming the successful entrapment
      of the biological component in the synthetic network. The porosity degree of the
      bioartificial membranes was also investigated by permeability tests and the
      effect of morphological characteristics on transport properties was studied.
      Water flux across the membranes, solute permeability and sieving coefficients
      were also calculated. The results revealed that the transport properties of these
      bioartificial membranes, obtained by the phase inversion method, could be
      controlled by mainly changing the preparation control parameters and the EVAL
      dextran ratio.

PMID- 20799228
TI  - Porous bovine hydroxyapatite for drug delivery.
AB  - Biomaterials derived from natural sources have considerable interest in human
      health care. This study reports a simple method of designing a bone drug delivery
      system using porous bovine hydroxyapatite (BHA). The porous BHA blocks with
      different porosity were fabricated by a die-pressing method using
      polyvinylbutyral (PVB) as a porosifier. A model antibiotic drug, neomycin sulfate
      (NS) was loaded in the blocks and its in vitro release performance was studied.
      Fourier transform infrared (FTIR) analysis provided qualitative proof of drug
      molecule entrapment in the BHA blocks. The in vitro evaluation of the drug
      indicated that the rate of drug loading and release was directly proportional to
      the porosity of the blocks.

PMID- 20799229
TI  - Gait analysis before and after gastrocnemius fascia lengthening in children with
      cerebral palsy.
AB  - Equinus deformity is a common problem in children with spastic cerebral palsy
      (CP). Persistent deformity that interferes with function is treated by surgically
      lengthening the triceps surae. Surgical approaches carry a recurrence risk of
      equinus deformity or over correction with the development of calcaneal deformity,
      crouch and diminished strength for push-off during gait. These aspects interfere
      with the basic function of the gastrocnemius/soleus complex. This study aimed to
      analyze kinematic and kinetic effects of gastrocnemius fascia lengthening on gait
      pattern in children with CP and, in particular, the evaluation of push-off
      ability before and after treatment. Twenty children with CP were evaluated by
      clinical examination and three-dimensional gait analysis (GA) before and after
      (12 months) gastrocnemius fascia lengthening surgery (modified Vulpius'
      technique) to improve equinus foot and walking. The results showed a significant
      reduction in equinus foot, represented by a re-duction in the a angle (the angle
      between the foot and the ground on the sagittal plane) at initial contact (IC),
      closer to healthy children, and increased ankle power generation during push-off.
      Even if this result was not of a statistically significant level, it is important
      because it means that the surgery did not produce a functional weakness. Kinetic
      results showed an improvement (ankle joint power absorbed and generated) related
      to a more functional walking behavior. Some improvements concerning the knee
      joint are significant, in particular, the value of the knee angle at IC and of
      peak during the swing phase.

PMID- 20799230
TI  - Hydration characteristics of alpha-tricalcium phosphates: Comparison of
      preparation routes.
AB  - Alpha tricalcium phosphate ( a -TCP) cement powders were obtained by solid state
      reaction and milling (M1) and by precipitation from aqueous solution followed by
      heating (M2). The materials were hydrated to form calcium-deficient
      hydroxyapatite (CDHA) with a 2.5 wt% solution of Na2 HPO4 (liquid to powder ratio
      = 0.34 ml/g, temperature = 37.5 degrees C) and subjected to isothermal
      calorimetry, mechanical compression tests, X-ray powder diffraction, at various
      times during hydration, as well as scanning electron microscopy (SEM), laser
      diffraction and gas adsorption. The particle characteristics of the two powders
      were similar, but M2 exhibited two reaction events in the thermal power curve,
      while M1 showed a single event. Both reaction events were attributed to a -TCP
      dissolution and CDHA recipitation. The minimum in the reaction rate response of
      M2 was probably due to the formation of a passivating product layer. No such
      layer was formed on the milled M1 due to its rougher surfaces. Both preparations
      reached a compressive strength of 30-40 MPa after 24 hr.

PMID- 20799231
TI  - Integrating live cells with semiconductor devices: A biocompatibility assay.
AB  - There is increasing interest in the development of small hybrid cell
      semiconductor systems for the non-invasive evaluation of the physiological state
      of a cell population. These miniature devices can be used in many areas of
      biomedical applications, ranging from basic research to drug screening during
      cancer chemosensitivity testing in clinics. A prerequisite for the biological and
      medical application of these devices is that cells retain their functional and
      growth properties when in contact with the semiconductor sensor material. The
      sensor surface is usually coated with dielectric silicon dioxide (SiO2 ) or a
      silicon nitride layer (Si3 N4 ); therefore, cellular adhesion to these materials
      and cellular viability on these surfaces are of crucial im-portance. This is
      especially true for bone cells that are sensitive to the surface microstructure.
      Therefore, we investigated the short-term (1-7 days) behavior of model bone cells
      (MG63 human osteosarcoma cells) grown on silicon samples coated with SiO2 . Cell
      adhesion and morphology were evaluated by scanning electron microscopy (SEM) 1
      day after seeding and cell pro-liferation was evaluated by Alamar Blue assay at
      2, 3 and 7 days after seeding. No adverse cellular reactions could be detected
      with these assays suggesting that the tested substrate is suitable for the hybrid
      cell-semiconductor systems that test bone tumor chemosensitivity.

PMID- 20799232
TI  - Periprosthetic bone remodeling. A finite elementstudy of the influence of the
      implant design.
AB  - Remodeling periprosthetic femoral bone after total hip arthroplasty has been
      studied extensively. Finite element (FE) analysis, together with mathematical
      remodeling theories, has predicted that femoral bone-mineral density decreases
      proximally after total hip arthroplasty. There is significant controversy
      concerning the clinical consequences of bone remodeling such as the reduction in
      bone strength, the possibility of a cement mantle fracture, the aseptic loosening
      of the implant, or the appearance of a periprosthetic fracture, which could
      threaten the survival of the hip prosthesis. The status of periprosthetic bone
      stock is an important concern when total hip arthroplasty revision is undertaken.
      This study was conducted to evaluate the periprosthetic bone-mineral density
      evolution following primary total hip arthroplasty by FE analysis. We compared
      two cemented stems with different designs: the Exeter and the SHP to study the
      phenomenon of femoral stress shielding and bone cement deterioration. We found
      that with the best mechanical conditions and with the same materials, the
      prosthesis design determines a different periprosthetic bone remodeling.

PMID- 20799233
TI  - Effects of Nd:YAG laser on dental enamel.
AB  - Caries prevention should be an important goal of the dentistry practitioner. In
      addition to traditional preventive techniques, laser beam has been a recent
      suggestion. This study aimed to evaluate Nd:YAG laser treatment effects on dental
      enamel surfaces, irradiated at different energy levels, by scanning electron
      microscopy (SEM) observations and surface micro-hardness tests to evaluate if
      caries prevention can be achieved by laser treatment. Forty human teeth were
      divided in four groups of 10 specimens each: in three groups the enamel surface
      was treated with three different laser beam energy levels, 60, 120 and 160 mJ, in
      one group the enamel was not lased. Five samples from each group were subjected
      to the Vickers microhardness test and five samples underwent SEM investigation.
      Results of the microhardness test demonstrated no significant differences between
      treated and non-treated dental enamel samples. SEM observation demonstrated a
      rougher enamel surface in all treated groups: the 60 mJ treated group showed
      tooth surfaces with vertical scratches, the 120 mJ treated group showed the
      enamel surface covered by craters and cracks, and the 160 mJ treated group showed
      a completely changed enamel structure with columns separated by voids and with a
      glass-like surface. These investigations demonstrated that dental enamel laser
      treatment at low energy levels (not >60 mJ) produces a protective glass-like
      surface, without the loss of its integrity and could be an advisable technique to
      prevent caries. Higher energy laser treatment leads to modifications of the
      enamel morphology such as craters and cracks, even if it does not cause any
      change in enamel hardness characteristics, which could be more useful in
      conservative dentistry.

PMID- 20799234
TI  - The microbial infection of biomaterials: A challenge for clinicians and
      researchers. A short review.
AB  - The increasing use of biomaterials and medical devices has led to the development
      of new families of diseases related precisely to the use of the biomaterials and
      medical devices themselves. Microbial contamination of the devices is a serious
      and widespread problem in surgery because it often causes devastating infections
      and loss of the implanted devices. The methods of contamination in medical
      devices are dependent on many peculiar factors including the chemistry of the
      biomaterial, the physical properties of the surface, the design of the medical
      device, the implanted anatomical site, the extension of surgical invasion, and
      the time of application. The environment and/or conditions and response of the
      host also contribute to the development of the colonization and infection. Many
      bacteria and fungi spp. are involved in biomaterial infections, but most belong
      to endogenous bacteria or the commensal community of the skin such as
      Staphylococcus epidermidis and Staphylococcus aureus. Medical device
      contamination always develops into biofilm formation, which constitutes a
      protected mode for the bacteria to survive in a hostile environment by optimizing
      nutrient uptake, as it is sheltered from the removal forces and is protected from
      the host defense mechanism and from potential toxic or harmful substances
      including antibiotics. Therefore, studies concerning infections related to
      implanted materials are of increasing frequency and interest. Both in vitro and
      in vivo studies are reported to simulate biomaterial infection. We report
      suggestions concerning useful standards and strategies to re-duce contamination
      on biomaterials. (Journal of Applied Biomaterials and Biomechanics 2005; 3: 1
      10).

PMID- 20799235
TI  - Stem cell factor receptor KIT (CD117) in aseptic hip prosthesis loosening.
AB  - OBJECTIVE: This study aimed to investigate specific inflammatory pathomechanisms,
      i.e. the expression of the stem cell factor receptor KIT (CD117) in tissue
      specimens from patients with aseptic hip prosthesis loosening (AHPL) with special
      emphasis on colocalization with the mast cell specific marker tryptase. METHODS:
      Immunohistochemical analysis of CD117 was performed in tissue specimens from 10
      patients with aseptically loosened acetabular components of failed non-cement
      total hip replacements and compared to control samples obtained at primary hip
      surgery (n=4). The CD117 expressing cells were characterized further with mast
      cell tryptase (MCT) by serial section analysis and a double staining method.
      CD117 and MCT expression was examined by semi-quantitative analysis.
      Additionally, double labeling of the CD117 or MCT expression by
      immunohistochemistry and of polyethylene (PE) particles by Oil Red reaction was
      performed. RESULTS: In AHPL, CD117 was almost exclusively detected in MCT
      positive cells. Co-expression tended to be highly correlated (r=0.86, p<0.01).
      CD117 was found mainly in two regions: first, in perivascular lymphocyte-rich
      areas and; secondly, near macrophages and multinucleated giant cells (MGC). PE
      particles were not detected in CD117 and MCT positive cells. In control samples,
      CD117/MCT positive cells were less frequent. CONCLUSION: This is the first report
      on CD117 expression in AHPL. CD117 is almost exclusively expressed in a distinct
      mast cell subgroup. As an important growth factor receptor, CD117 could play a
      major role in recruitment and activation of mast cells in AHPL. Furthermore, mast
      cells do not contain significant amounts of PE particles. However, it remains to
      be investigated whether this cell population could influence phagocytosis of PE
      particles. (Journal of Applied Biomaterials and Biome-chanics 2005; 3: 11-7).

PMID- 20799236
TI  - Bone tissue responses to Mg-incorporated oxidized implants and machine-turned
      implantsin the rabbit femur.
AB  - Previous studies have demonstrated a significant improvement in the bone response
      to oxidized titanium implants. Little is known about the effects of specific
      oxide properties on the bone tissue responses to titanium implants. This study in
      vestigated the bone tissue responses to magnesium (Mg)-incorporated oxidized
      titanium implants and machine-turned titani-um implants in the rabbit femur. The
      oxidized implants were prepared using micro arc oxidation (MAO) methods. Surface
      oxide properties were characterized by using various surface analytic techniques,
      involving scanning electron microscopy (SEM) equipped with energy dispersive
      spectrometer (EDS), X-ray diffractometry (XRD), X-ray photoelectron spectroscopy
      (XPS) and optical interferometry. Screw shaped titanium implants, 10 machine
      turned implants (controls) and 10 Mg-incorporated im-plants (tests) were inserted
      in the femoral condyles of 10 New Zealand white rabbits. After a 6-week healing
      period, resonance frequency analyses and removal torque measurements of the Mg
      incorporated oxidized implants demonstrated significant im-provements in implant
      integration with bone in comparison to machine-turned implants, p=0.007 and
      p=0.017, respectively. Bone growth in the pores of the oxidized implants was
      probably incomplete at a follow-up of 6 weeks, as indicated by SEM and EDS
      measurements. Mg-incorporated titanium implants significantly improved bone
      responses as compared with machine-turned control implants. Considering the
      differences and similarities of the surface oxide properties of controls and test
      im-plants, the enhanced bone responses to Mg-incorporated implants could be
      explained by the Mg surface chemistry of the test im-plants. (Journal of Applied
      Biomaterials and Biomechanics 2005; 3: 18-28).

PMID- 20799237
TI  - Cytotoxic and genotoxic effects of the exposure of human lymphocytes to a calcium
      phosphate cement in vitro.
AB  - The cytotoxic and genotoxic effects of a phosphate bone cement on human
      peripheral lymphocyte cultures exposed for 48 hr were determined. The mitotic
      index and the integrity of the DNA molecule were used as biocompatibility
      markers. It was found that the cement was not cytotoxic, but genotoxic at
      concentrations of >/=100 microg/ml. The cement was also characterized using
      scanning electron microscopy (SEM) and X-ray diffraction (XRD). (Journal of
      Applied Biomaterials and Biomechanics 2005; 3: 29-34).

PMID- 20799238
TI  - Evaluation of bioresorbable implants from bovine bone: In vitro preliminary
      observations.
AB  - Biocompatibility evaluation is a fundamental step in developing new biomaterials.
      Implants derived from bovine tibial compact bone were analyzed with in vitro
      tests using fibroblast and osteoblast-like cells. Initially, cell attachment and
      proliferation were quantified. Results indicated that the pins did not interfere
      with normal cell adhesion and proliferation; more-over, cell morphology was
      observed using scanning electron microscopy (SEM) and confocal fluorescence
      microscopy. In vivo experiments to evaluate material osteointegration are
      currently in progress. (Journal of Applied Biomaterials and Biomechanics 2005; 3:
      35-41).

PMID- 20799239
TI  - Endothelial cell adhesion force estimation at the nanoscale.
AB  - Endothelial cell adhesion to a synthetic surface includes a definite set of
      molecular interactions. Cell adhesion is managed by fibronectin and vitronectin
      in extracellular matrix (ECM) that binds the receptor site of the trans-membrane
      protein dimers, the integrins. These proteins contain one of the binding sites (I
      like domain receptor) for the Arg-Gly-Asp (RGD) peptides that are the established
      adhesion receptor sites in the ECM. A molecular approach can quantify the
      adhesion strength by ligand-receptor force computation. The molecular interaction
      energy between a polyethylene (PE) surface covalently grafted with the adhesion
      sites (RGD-containing) and trans-membrane integrin receptor (I-domain) was
      evaluated through a molecular model of a single ligand-receptor complex. The aims
      of this work were: (i) the generation of the receptor molecular model: the I-like
      domain; (ii) the evaluation of the greatest binding chemical affinity between the
      I-like domain and three RGD-containing peptides; (iii) the development of the
      molecular model of crystalline lamellae of PE; and (iv) the evaluation of the
      interac-tion energies and the interaction force between the I-like domain and the
      grafted biomaterial. The calculation of the interaction energies can provide an
      estimation of the adhesion force of the ligand-receptor complex and, finally, of
      the endothelial cell adhesion force. The calculated cell adhesion force is in
      agreement with experimental data.(Journal of Applied Biomaterials and
      Biomechanics 2005; 3: 42-9).

PMID- 20799240
TI  - Pins composed of poly(L-lactic acid)/poly(3- hydroxybutyrate-co-hydroxyvalerate)
      PLLA/PHBV blends: Degradation in vitro.
AB  - Bioabsorbable polymers have shown good clinical success in the fixation and
      stabilization of bone fractures. Understanding and controlling polymer prosthetic
      degradation and the effect of the degradation products in vivo are crucial for
      successful implant developments. In this study, pins made from blends of
      PLLA/PHBV of varying compositions were degraded in phosphate buffer and
      characterized by thermogravimetric analysis (TGA), differential scanning
      calorimetry (DSC), dynamic mechanical analysis (DMA) and scanning electron
      microscopy (SEM). The PLLA/PHBV blends were found to be immiscible. PLLA began to
      degrade after approximately 12 weeks, whereas PHBV showed some degradation only
      after 53 weeks. The crystallinity of the blends increased with degradation. In
      conclusion, PHBV improved the thermal properties of PLLA and reduced the
      brittleness of the blends tested. The 40/60 PLLA/PHBV blend had the best
      properties for use in orthopedics since it degraded quicker than pure PHBV, and
      yet maintained its crystallinity for longer than PLLA; in addition, this blend
      did not have the brittleness of PLLA. (Journal of Applied Biomaterials and
      Biomechanics 2005; 3: 50-60).

PMID- 20799241
TI  - Plantar pressure distribution in patients with neuropathic diabetic foot.
AB  - PURPOSE: To describe the plantar pressure distribution in a selected group of
      patients with diabetic foot and to highlight their alterations in gait cycle,
      which follow the involvement of the foot in systemic diabetic neuropathy.
      METHODS: Ten patients with diabetic foot due to insulin dependent diabetes
      mellitus (IDDM) were studied. Gait cycle kinematics were video-recorded, both in
      frontal (AP view) and in sagittal (LL view) planes. Plantar pressure
      measurements+ APview+LLview were synchronized and compared to a computer-graphic
      generated skeletal model of the foot. RESULTS: In diabetic neuropathic patients,
      there was a prolonged interval between heel strike and toe-off with respect to
      normal controls. A limited motion, quite close to frank rigidity, affecting the
      mid-tarsal, sub-talar and ankle joints was noted. There was an early transfer of
      load from rear to front-foot. Shear stresses appeared. Metatarsal heads were
      overloaded both in mag-nitude and in time. Areas of overload present in the
      static plantar pressure measurement correlated poorly with areas of over-load in
      dynamic plantar pressure measurement and areas where ulceration was present.
      CONCLUSION: Prolonged duration of the gait cycle and shear stresses characterize
      the plantar pressure pattern of diabetic neuropathic patients. Furthermore,
      results suggest that static plantar pressure measurement has no clinical
      correlation with areas where ulcerations are present. (Journal of Applied
      Biomaterials and Biomechanics 2005; 3: 61-4).

PMID- 20799242
TI  - Fate of bone marrow mesenchymal stem cells following the allogeneic
      transplantation of cartilaginous aggregates into osteochondral defects of
      rabbits.
AB  - The purpose of this study was to track mesenchymal stem cells (MSCs) labelled
      with internalizing quantum dots (i-QDs) in the reparative tissues, following the
      allogeneic transplantation of three-dimensional (3D) cartilaginous aggregates
      into the osteochondral defects of rabbits. QDs were conjugated with a unique
      internalizing antibody against a heat shock protein-70 (hsp70) family stress
      chaperone, mortalin, which is upregulated and expressed on the surface of
      dividing cells. The i-QDs were added to the culture medium for 24 h. Scaffold
      free cartilaginous aggregates formed from i-QD-labelled MSCs (i-MSCs), using a 3D
      culture system with chondrogenic supplements for 1 week, were transplanted into
      osteochondral defects of rabbits. At 4, 8 and 26 weeks after the transplantation,
      the reparative tissues were evaluated macroscopically, histologically and
      fluoroscopically. At as early as 4 weeks, the defects were covered with a white
      tissue resembling articular cartilage. In histological appearance, the reparative
      tissues resembled hyaline cartilage on safranin-O staining throughout the 26
      weeks. In the deeper portion, subchondral bone and bone marrow were well
      remodelled. On fluoroscopic evaluation, QDs were tracked mainly in bone marrow
      stromata, with some signals detected in cartilage and the subchondral bone layer.
      We showed that the labelling of rabbit MSCs with anti-mortalin antibody
      conjugated i-QDs is a tolerable procedure and provides a stable fluorescence
      signal during the cartilage repair process for up to 26 weeks after
      transplantation. The results suggest that i-MSCs did not inhibit, and indeed
      contributed to, the regeneration of osteochondral defects.

PMID- 20799243
TI  - Cognitive dysfunction in patients with type 2 diabetes.
AB  - People with diabetes mellitus are at increased risk of cognitive dysfunction and
      dementia. This review explores the nature and severity of cognitive changes in
      patients with type 2 diabetes. Possible risk factors such as hypo- and
      hyperglycemia, vascular risk factors, micro- and macrovascular complications,
      depression and genetic factors will be examined, as well as findings from brain
      imaging and autopsy studies. We will show that type 2 diabetes is associated with
      modest cognitive decrements in non-demented patients that evolve only slowly over
      time, but also with an increased risk of more severe cognitive deficits and
      dementia. There is a dissociation between these two 'types' of cognitive
      dysfunction with regard to affected age groups and course of development.
      Therefore, we hypothesize that the mild and severe cognitive deficits observed in
      patients with type 2 diabetes reflect separate processes, possibly with different
      risk factors and aetiologies.

PMID- 20799244
TI  - Sequential generalized likelihood ratio tests for vaccine safety evaluation.
AB  - The evaluation of vaccine safety involves pre-clinical animal studies, pre
      licensure randomized clinical trials, and post-licensure safety studies.
      Sequential design and analysis are of particular interest because they allow
      early termination of the trial or quick detection that the vaccine exceeds a
      prescribed bound on the adverse event rate. After a review of the recent
      developments in this area, we propose a new class of sequential generalized
      likelihood ratio tests for evaluating adverse event rates in two-armed pre
      licensure clinical trials and single-armed post-licensure studies. The proposed
      approach is illustrated using data from the Rotavirus Efficacy and Safety Trial.
      Simulation studies of the performance of the proposed approach and other methods
      are also given.

PMID- 20799245
TI  - Reference range of birth weight with gestation and first-trimester prediction of
      small-for-gestation neonates.
AB  - OBJECTIVE: Firstly, to establish a reference range of birth weight with gestation
      at delivery; secondly, to identify maternal characteristics that are
      significantly associated with birth weight; and thirdly, to determine if
      combinations of maternal characteristics, fetal nuchal translucency thickness
      (NT), and serum concentrations of free beta-human chorionic gonadotrophin (beta
      hCG) and pregnancy-associated plasma protein-A (PAPP-A) are significant
      predictors of small-for-gestational-age (SGA) neonates in the absence of
      preeclampsia. METHOD: Maternal characteristics were recorded; fetal NT, maternal
      serum free beta-hCG and PAPP-A were measured at 11 weeks to 13 weeks 6 days in
      33,602 women with singleton pregnancies. Regression analysis was used to
      determine the association of birth weight with gestation at delivery and to
      establish a reference range with gestation. Logistic regression analysis was used
      to determine if maternal factors, fetal NT, free beta-hCG, and PAPP-A contribute
      significantly in predicting SGA in the absence of preeclampsia. RESULTS: Birth
      weight increased with maternal weight and height; it was higher in parous than in
      nulliparous women and in those with a medical history of pre-pregnancy diabetes
      mellitus, and it was lower in cigarette smokers, in all racial groups other than
      in Caucasian women, and in those with a medical history of chronic hypertension
      and in those who previously delivered SGA neonates. In the SGA group compared
      with the unaffected group, there were lower median delta NT (0.10 vs 0.12 mm),
      free beta-hCG [0.9 vs 1.0 MoM (multiples of median)], and PAPP-A (0.8 vs 1.0
      MoM). The prediction of SGA provided by maternal factors was significantly
      improved by the addition of fetal NT and PAPP-A (34.0 vs 37.0% at a false
      positive rate of 10%). CONCLUSION: Prediction of the birth of SGA neonates in the
      absence of preeclampsia can be provided in the first trimester of pregnancy by a
      combination of maternal characteristics and measurements of parameters used in
      early screening for aneuploidies.

PMID- 20799246
TI  - Monitoring of QoI fungicide resistance in Plasmopara viticola populations in
      Japan.
AB  - BACKGROUND: The increasing occurrence of QoI fungicide resistance in Plasmopara
      viticola (Berk. & MA Curtis) Berl. & DeToni populations is becoming a serious
      problem in the control of grapevine downy mildew. In Japan, the existence of QoI
      fungicide-resistant P. viticola was reported in 2009. RESULTS: The QoI fungicide
      resistance in P. viticola samples collected from vineyards in Japan in 2008 and
      2009 was monitored. Resistant P. viticola were detected in the regions where QoI
      fungicides have been introduced in accordance with the pest management programme,
      whereas in Hokkaido vineyards, where QoI fungicides have not yet been introduced,
      QoI-fungicide-resistant P. viticola were not found. CONCLUSION: Japan comprises
      thousands of islands and is physically isolated from other countries by the sea.
      Monitoring the emergence, incidence and distribution of QoI fungicide resistance
      in P. viticola populations in Japan is necessary to improve pest management
      strategies for downy mildew disease in Japanese vineyards.

PMID- 20799247
TI  - Incidence and characterisation of resistance to neonicotinoid insecticides and
      pymetrozine in the greenhouse whitefly, Trialeurodes vaporariorum Westwood
      (Hemiptera: Aleyrodidae).
AB  - BACKGROUND: Trialeurodes vaporariorum (Westwood), also known as the greenhouse
      whitefly, is a serious pest of protected vegetable and ornamental crops in most
      temperate regions of the world. Neonicotinoid insecticides are used widely to
      control this species, although resistance has been reported and may be becoming
      widespread. RESULTS: Mortality rates of UK and European strains of T.
      vaporariorum to a range of neonicotinoids and pymetrozine, a compound with a
      different mode of action, were calculated, and significant resistance was found
      in some of those strains. A strong association was found between neonicotinoids
      and pymetrozine, and reciprocal selection experiments confirmed this finding.
      Expression of resistance to the neonicotinoid imidacloprid and pymetrozine was
      age specific, and resistance in nymphs did not compromise recommended application
      rates. CONCLUSION: This study indicates strong parallels in the phenotypic
      characteristics of neonicotinoid resistance in T. vaporariorum and the tobacco
      whitefly Bemisia tabaci Gennadius, suggesting possible parallels in the
      underlying mechanisms.

PMID- 20799248
TI  - Slope estimation in structural line-segment heteroscedastic measurement error
      models.
AB  - This paper extends the line-segment parametrization of the structural measurement
      error (ME) model to situations in which the error variance on both variables is
      not constant over all observations. Under these conditions, we develop a method
      of-moments estimate of the slope, and derive its asymptotic variance. We further
      derive an accurate estimator of the variability of the slope estimate based on
      sample data in a rather general setting. We perform simulations that validate our
      results and demonstrate that our estimates are more precise than estimates under
      a different model when the ME variance is not small. Finally, we illustrate our
      estimation approach using real data involving heteroscedastic ME, and compare its
      performance with that of earlier models.

PMID- 20799249
TI  - A Bayesian approach to simultaneously adjusting for verification and reference
      standard bias in diagnostic test studies.
AB  - Verification bias arises in diagnostic test evaluation studies when the results
      from a first test are verified by a reference test only in a non-representative
      subsample of the original study subjects. This occurs, for example, when
      inclusion probabilities for the subsample depend on first-stage results and/or on
      a covariate related to disease status. Reference standard bias arises when the
      reference test itself has imperfect sensitivity and specificity, but this
      information is ignored in the analysis. Reference standard bias typically results
      in underestimation of the sensitivity and specificity of the test under
      evaluation, since subjects that are correctly diagnosed by the test can be
      considered as misdiagnosed owing to the imperfections in the reference standard.
      In this paper, we describe a Bayesian approach for simultaneously addressing both
      verification and reference standard bias. Our models consider two types of
      verification bias, first when subjects are selected for verification based on
      initial test results alone, and then when selection is based on initial test
      results and a covariate. We also present a model that adjusts for a third
      potential bias that arises when tests are analyzed assuming conditional
      independence between tests, but some dependence exists between the initial test
      and the reference test. We examine the properties of our models using simulated
      data, and then apply them to a study of a screening test for dementia, providing
      bias-adjusted estimates of the sensitivity and specificity.

PMID- 20799250
TI  - Regression analysis of clustered interval-censored data with informative cluster
      size.
AB  - Interval-censored data are commonly found in studies of diseases that progress
      without symptoms, which require clinical evaluation for detection. Several
      techniques have been suggested with independent assumption. However, the
      assumption will not be valid if observations come from clusters. Furthermore,
      when the cluster size relates to response variables, commonly used methods can
      bring biased results. For example, in a study on lymphatic filariasis, a
      parasitic disease where worms make several nests in the infected person's
      lymphatic vessels and reside until adulthood, the response variable of interest
      is the nest-extinction times. As the extinction times of nests are checked by
      repeated ultrasound examinations, exact extinction times are not observed.
      Instead, data are composed of two examination points: the last examination time
      with living worms and the first examination time with dead worms. Furthermore, as
      Williamson et al. (Statistics in Medicine 2008; 27:543-555) pointed out, larger
      nests show a tendency for low clearance rates. This association has been denoted
      as an informative cluster size. To analyze the relationship between the numbers
      of nests and interval-censored nest-extinction times, this study proposes a joint
      model for the relationship between cluster size and clustered interval-censored
      failure data. A proportional hazard model with random effect and a mixed ordinal
      regression model are applied to failure times and cluster size, respectively. The
      joint model approach addresses both the association among failure times from the
      same cluster and the dependency of failure times on cluster size. Simulation
      studies are performed to assess the finite sample properties of the estimators
      and lymphatic filariasis data are analyzed as an illustration.

PMID- 20799251
TI  - Identification of new limonoids from Swietenia and their biological activity
      against insects.
AB  - BACKGROUND: Natural limonoids are one group of compounds being studied for their
      insecticidal properties. To discover new limonoids with better activities,
      analogs were prepared via acylation and hydrolysis, and bioassayed. RESULTS:
      Analogs were identified using one- and two-dimensional (COSY, HMQC and HMBC) (1)
      H and (13) C NMR, IR and MS. 3-O-Isovalerylswietenolide (13) and 3-O
      isobutyrylswietenolide (14) showed excellent antifeedant activity, with DC(50)
      values of 0.19 and 0.009 mg L(-1) respectively, compared with the natural
      limonoid swietenolide (80.6 mg L(-1) ) against fourth-instar Spodoptera
      frugiperda (JE Smith) larvae. CONCLUSION: This work shows that limonoid analogs
      prepared through semi-synthesis can be used as lead compounds for the development
      of new insecticides.

PMID- 20799252
TI  - Validation of the in vivo assessment of pyruvate dehydrogenase activity using
      hyperpolarised 13C MRS.
AB  - Many diseases of the heart are characterised by changes in substrate utilisation,
      which is regulated in part by the activity of the enzyme pyruvate dehydrogenase
      (PDH). Consequently, there is much interest in the in vivo evaluation of PDH
      activity in a range of physiological and pathological states to obtain
      information on the metabolic mechanisms of cardiac diseases. Hyperpolarised [1
      (13)C]pyruvate, detected using MRS, is a novel technique for the noninvasive
      evaluation of PDH flux. PDH flux has been assumed to directly reflect in vivo PDH
      activity, although to date this assumption remains unproven. Control animals and
      animals undergoing interventions known to modulate PDH activity, namely high fat
      feeding and dichloroacetate infusion, were used to investigate the relationship
      between in vivo hyperpolarised MRS measurements of PDH flux and ex vivo
      measurements of PDH enzyme activity (PDH(a)). Further, the plasma concentrations
      of pyruvate and other important metabolites were evaluated following pyruvate
      infusion to assess the metabolic consequences of pyruvate infusion during
      hyperpolarised MRS experiments. Hyperpolarised MRS measurements of PDH flux
      correlated significantly with ex vivo measurements of PDH(a), confirming that PDH
      activity influences directly the in vivo flux of hyperpolarised pyruvate through
      cardiac PDH. The maximum plasma concentration of pyruvate reached during
      hyperpolarised MRS experiments was approximately 250 uM, equivalent to
      physiological pyruvate concentrations reached during exercise or with dietary
      interventions. The concentrations of other metabolites, including lactate,
      glucose and beta-hydroxybutyrate, did not vary during the 60 s following pyruvate
      infusion. Hence, during the 60-s data acquisition period, metabolism was
      minimally affected by pyruvate infusion.

PMID- 20799253
TI  - Melt processing of chitosan-based fibers and fiber-mesh scaffolds for the
      engineering of connective tissues.
AB  - We report the production of chitosan-based fibers and chitosan fiber-mesh
      structures by melt processing (solvent-free) to be used as tissue-engineering
      scaffolds. The melt-based approach used to produce the scaffolds does not change
      their main characteristics, including the surface roughness and microporosity.
      The porosity, pore size, interconnectivity and mechanical performance of the
      scaffolds are all within the range required for various tissue-engineering
      applications. Biological assessments are performed in direct-contact assays.
      Cells are able to colonize the scaffold, including the inner porous structure.
      The cells show high indices of viability in all of the scaffold types.

PMID- 20799255
TI  - Fabrication of bioactive composite scaffolds by electrospinning for bone
      regeneration.
AB  - Electrospun scaffolds are widely used for various biomedical applications. In
      this study, we prepared electrospun bioactive composite scaffolds combining
      hydroxyapatite, collagen (Col) and a synthetic polymer-PolyActiveTM-to mimic
      naturally occurring extracellular matrix for in situ bone regeneration. Human
      mesenchymal stem cells (hMSCs) adhered and proliferated on these scaffolds. Cells
      on all scaffold types showed an increased metabolic activity with time. On day 4,
      the metabolic activity of cells cultured on PolyActiveTM (PA)-hydroxyapatite (HA)
      Col in 1,1,1,3,3,3-hexafluoro-2-propanolhexafluoro-2-propanol (HFIP) was
      significantly higher than that of cells grown on PA-Col samples. Furthermore, on
      day 6, cells on PA-HA-Col in HFIP showed significantly higher metabolic activity
      than those on PA and PA-Col scaffolds. Quantitative PCR analysis for a panel of
      osteogenic genes showed statistically significant differences between scaffolds.
      Cells cultured on PA-HA scaffolds had a significantly higher osteonectin and
      RunX2 expression compared to those on PA-HA-Col scaffolds. Cells on PA-HA-Col in
      HFIP scaffolds had significantly higher expression of alkaline phosphatase (ALP)
      and Col 1 compared to PA and PA-Col scaffolds respectively. The bone
      morphogenetic protein-2 and S100A4 expression of PA-Col and PA-HA-Col constructs
      was significantly lower than the basal level expression of cells on PA scaffolds.
      Although not statistically significant in all cases, cells cultured on PA-HA-Col
      in HFIP and PA-HA scaffolds had the highest expression for most of the genes
      analysed. The results of the study demonstrate that bioactive composite scaffolds
      prepared by electrospinning could find potential use in bone regeneration
      applications.

PMID- 20799256
TI  - Polymers in biomedicine.

PMID- 20799254
TI  - The matrix-binding domain of microfibril-associated glycoprotein-1 targets active
      connective tissue growth factor to a fibroblast-produced extracellular matrix.
AB  - It is advantageous to use biomaterials in tissue engineering that stimulate
      extracellular matrix (ECM) production by the cellular component. Connective
      tissue growth factor (CTGF) stimulates type I collagen (COL1A1) transcription,
      but is functionally limited as a free molecule. Using a matrix-binding domain
      (MBD) from microfibril-associated glycoprotein-1, the fusion protein MBD-CTGF was
      targeted to the ECM and tested for COL1A1 transcriptional activation. MBD-CTGF
      produced by the ECM-synthesizing fibroblasts, or provided exogenously, localized
      to the elastic fiber ECM. MBD-CTGF, but not CTGF alone, led to a two-fold
      enhancement of COL1A1 expression. This study introduces a targeting technology
      that can be used to elevate collagen transcription in engineered tissues and
      thereby improve tissue mechanics.

PMID- 20799257
TI  - Interval estimation of quantile ratios applied to anti-cancer drug screening by
      xenograft experiments.
AB  - The current practice in analyzing data from anti-cancer drug screening by
      xenograft experiments lacks statistical consideration to account for experimental
      noise, and a sound inference procedure is necessary. A novel confidence bound and
      interval procedure for estimating quantile ratios developed in this paper fills
      the void. Justified by rigorous large-sample theory and a simulation study of
      small-sample performance, the proposed method performs well in a wide range of
      scenarios involving right-skewed distributions. By providing rigorous inference
      and much more interpretable statistics that account for experimental noise, the
      proposed method improves the current practice of analyzing drug activity data in
      xenograft experiments. The proposed method is fully nonparametric, simple to
      compute, performs equally well or better than known nonparametric methods, and is
      applicable to any statistical inference of a 'fold change' that can be formulated
      as a quantile ratio.

PMID- 20799258
TI  - Sample size determination in step-up testing procedures for multiple comparisons
      with a control.
AB  - Step-up procedures have been shown to be powerful testing methods in clinical
      trials for comparisons of several treatments with a control. In this paper, a
      determination of the optimal sample size for a step-up procedure that allows a
      pre-specified power level to be attained is discussed. Various definitions of
      power, such as all-pairs power, any-pair power, per-pair power and average power,
      in one- and two-sided tests are considered. An extensive numerical study confirms
      that square root allocation of sample size among treatments provides a better
      approximation of the optimal sample size relative to equal allocation. Based on
      square root allocation, tables are constructed, and users can conveniently obtain
      the approximate required sample size for the selected configurations of
      parameters and power. For clinical studies with difficulties in recruiting
      patients or when additional subjects lead to a significant increase in cost, a
      more precise computation of the required sample size is recommended. In such
      circumstances, our proposed procedure may be adopted to obtain the optimal sample
      size. It is also found that, contrary to conventional belief, the optimal
      allocation may considerably reduce the total sample size requirement in certain
      cases. The determination of the required sample sizes using both allocation rules
      are illustrated with two examples in clinical studies.

PMID- 20799259
TI  - Weighted Kaplan-Meier estimators for two-stage treatment regimes.
AB  - In two-stage randomization designs, patients are randomized to one of the initial
      treatments, and at the end of the first stage, they are randomized to one of the
      second stage treatments depending on the outcome of the initial treatment.
      Statistical inference for survival data from these trials uses methods such as
      marginal mean models and weighted risk set estimates. In this article, we propose
      two forms of weighted Kaplan-Meier (WKM) estimators based on inverse-probability
      weighting-one with fixed weights and the other with time-dependent weights. We
      compare their properties with that of the standard Kaplan-Meier (SKM) estimator,
      marginal mean model-based (MM) estimator and weighted risk set (WRS) estimator.
      Simulation study reveals that both forms of weighted Kaplan-Meier estimators are
      asymptotically unbiased, and provide coverage rates similar to that of MM and WRS
      estimators. The SKM estimator, however, is biased when the second randomization
      rates are not the same for the responders and non-responders to initial
      treatment. The methods described are demonstrated by applying to a leukemia data
      set.

PMID- 20799260
TI  - An easy-to-implement approach for analyzing case-control and case-only studies
      assuming gene-environment independence and Hardy-Weinberg equilibrium.
AB  - The case-control study is a simple and an useful method to characterize the
      effect of a gene, the effect of an exposure, as well as the interaction between
      the two. The control-free case-only study is yet an even simpler design, if
      interest is centered on gene-environment interaction only. It requires the
      sometimes plausible assumption that the gene under study is independent of
      exposures among the non-diseased in the study populations. The Hardy-Weinberg
      equilibrium is also sometimes reasonable to assume. This paper presents an easy
      to-implement approach for analyzing case-control and case-only studies under the
      above dual assumptions. The proposed approach, the 'conditional logistic
      regression with counterfactuals', offers the flexibility for complex modeling yet
      remains well within the reach to the practicing epidemiologists. When the dual
      assumptions are met, the conditional logistic regression with counterfactuals is
      unbiased and has the correct type I error rates. It also results in smaller
      variances and achieves higher powers as compared with using the conventional
      analysis (unconditional logistic regression).

PMID- 20799261
TI  - Tuftsin derivatives of FITC, Tb-DOTA or Gd-DOTA as potential macrophage-specific
      imaging biomarkers.
AB  - Fluorescein- and terbium-labelled tuftsin (Thr-Lys-Pro-Arg) and pentapeptide (Thr
      Lys-Pro-Pro-Arg) were synthesized and their properties were evaluated in vitro by
      luminescence spectrometry and confocal microscopy as fluorescence probes to
      target macrophage cells in biological systems. An increase in fluorescence of
      macrophages incubated with varying concentrations of fluorescein isothiocyanate
      or Tb-DOTA-tuftsin/pentapeptide conjugates was observed in a concentration
      dependent manner. Tb-DOTA-pentapeptide had a greater affinity to macrophages than
      Tb-DOTA-tuftsin. Lipopolysaccharide (LPS) stimulation strengthened the
      internalization of peptide conjugates by macrophages through the tuftsin receptor
      mechanism. Tb-DOTA-tuftsin/pentapeptide conjugates are likely to be a promising
      optical reagents as probes of the immune response with involvement of macrophage
      cells in a variety of diseases. Gd-DOTA-tuftsin conjugate was also evaluated as a
      cell-specific contrast agent in in vitro MRI experiments. In this context, the
      macrophages labelled by Gd-DOTA-tuftsin were highly magnetic and detectable by
      MRI, which confirms that this vectorized MRI probe has the potential to image
      macrophage-mediated inflammation in diseases like brain traumas and stroke.
      Tuftsin receptor-specific biological-function domain may have a modified in vivo
      biodistribution profile, bioavailability and pharmacokinetics subsequent to its
      conjugation to a metal ion-binding backbone.

PMID- 20799262
TI  - The Computerised Manchester Child Attachment Story Task: a novel medium for
      assessing attachment patterns.
AB  - The Manchester Child Attachment Story Task (MCAST) is a representational
      technique for assessing attachment patterns of young school-age children. We have
      developed a computerised version (the CMCAST) in which story stems are
      represented on the computer by the movement of simple screen 'dolls'. This paper
      reports on a preliminary validation study of the CMCAST method against the MCAST.
      Fifty-five children completed the MCAST and CMCAST six weeks apart in random
      order. It proved possible to rate the CMCAST if a simplified form of the MCAST
      coding system was used. Inter-rater reliability was achieved for both versions
      (kappa = 0.93 for MCAST and kappa = 0.91 for CMCAST). Agreement between the MCAST
      and CMCAST ratings of attachment security was kappa = 0.67. Costs for the MCAST
      and CMCAST were comparable. A school-based feasibility study of 86 children
      suggested that the CMCAST was acceptable and could be administered with up to
      five children simultaneously. This preliminary study suggests that the CMCAST can
      reliably reproduce a simplified form of MCAST coding. The computer format may be
      well adapted to some uses such as screening for large-scale epidemiological
      research.

PMID- 20799263
TI  - Reading and visual processing in Greek dyslexic children: an eye-movement study.
AB  - We examined the impact of the effects of dyslexia on various processing and
      cognitive components (e.g., reading speed and accuracy) in a language with high
      phonological and orthographic consistency. Greek dyslexic children were compared
      with a chronological age-matched group on tasks that tested participants'
      phonological and orthographic awareness during reading and spelling, as well as
      their efficiency to detect a specific target-letter during a sequential visual
      search task. Dyslexic children showed impaired reading and spelling that was
      reflected in slow reading speed and error-prone performance, especially for non
      words. Eye movement measures of text reading also provided supporting evidence
      for a reading deficit, with dyslexic participants producing more fixations and
      longer fixation duration as opposed to non-dyslexic participants. The results of
      the visual search task showed similar performance between the two groups, but
      when they were compared with the results of text reading, dyslexic participants
      were found to be able to process fewer stimuli (i.e., letters) at each fixation
      than non-dyslexics. Our findings further suggest that, although Greek dyslexics
      have the advantage of a consistent orthographic system which facilitates
      acquisition of reading and phonological awareness, they demonstrate more impaired
      access to orthographic forms than dyslexics of other transparent orthographies.

PMID- 20799264
TI  - American College of Rheumatology hybrid analysis of certolizumab pegol plus
      methotrexate in patients with active rheumatoid arthritis: data from a 52-week
      phase III trial.
AB  - OBJECTIVE: The American College of Rheumatology (ACR) hybrid (a modified mean
      percent response to treatment) was officially recommended by the ACR as a
      revision to 20%, 50%, and 70% response criteria (ACR20/50/70) scores, but has not
      been tested in clinical trials. We performed a post hoc analysis of a phase III
      study of certolizumab pegol (Rheumatoid Arthritis Prevention of Structural Damage
      1 [RAPID 1]) using the ACR hybrid. METHODS: Patients with active rheumatoid
      arthritis were randomized to certolizumab pegol (200 mg or 400 mg every other
      week) plus methotrexate or placebo plus methotrexate. ACR hybrid scores were
      compared with ACR20/50/70 outcomes. RESULTS: Differences between active treatment
      and placebo were significant throughout the study using the ACR20 and ACR hybrid
      outcomes. In the certolizumab pegol 200 mg group, the median ACR hybrid score at
      week 52 (last observation carried forward) was 49.99. A total of 258 (65.8%) of
      392 and 172 (43.9%) of 392 patients had ACR20 and ACR50 responses, respectively.
      An additional 55 patients (14.0%) and 59 patients (15.1%) had mean improvements
      in ACR core measures of >= 20% and >= 50%, respectively, and therefore had
      positive ACR hybrid scores, despite lacking ACR20 and ACR50 responses,
      respectively. In the placebo group, median ACR hybrid scores were <10 at most
      time points; unlike other measures, the ACR hybrid measure indicated worsening
      scores for many patients. CONCLUSION: ACR hybrid analysis had greater sensitivity
      than traditional ACR20/50/70 criteria, demonstrating improvements in ACR20
      nonresponders treated with certolizumab pegol. Negligible benefit was observed
      with placebo using ACR hybrid analysis.

PMID- 20799266
TI  - Maintenance of fertility in patients with rheumatic diseases needing
      antiinflammatory and immunosuppressive drugs.

PMID- 20799265
TI  - Low back pain and other musculoskeletal pain comorbidities in individuals with
      symptomatic osteoarthritis of the knee: data from the osteoarthritis initiative.
AB  - OBJECTIVE: To examine the association of concurrent low back pain (LBP), and
      other musculoskeletal pain comorbidity, with knee pain severity in symptomatic
      knee osteoarthritis (OA). METHODS: Individuals from the Progression Cohort of the
      Osteoarthritis Initiative (n=1,389, ages 45-79 years) with symptomatic
      tibiofemoral knee OA were studied. Participants identified pain in the low back,
      neck, shoulder, elbow, wrist, hand, hip, knee, ankle, or foot. The primary
      outcome was the pain subscale of the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) applied to the more symptomatic knee. We examined
      WOMAC pain score in persons with and without LBP, before and after adjusting for
      other musculoskeletal symptoms. RESULTS: Of the participants, 57.4% reported LBP.
      The mean+/-SD WOMAC pain score (possible range 0-20) was 6.5+/-4.1 in
      participants with and 5.2+/-3.4 in participants without LBP (P<0.0001). In
      multivariate analyses, LBP was significantly associated with increased WOMAC knee
      pain score (beta [SE]=1.00 [0.21], P<0.0001). However, pain in all other
      individual musculoskeletal locations demonstrated similar associations with knee
      pain score. In models including all pain locations simultaneously, only LBP (beta
      [SE]=0.65 [0.21], P=0.002), ipsilateral elbow pain (beta [SE]=0.98 [0.40],
      P=0.02), and ipsilateral foot pain (beta [SE]=1.03 [0.45], P=0.02) were
      significantly associated with knee pain score. Having >1 pain location was
      associated with greater WOMAC knee pain; this relationship was strongest for
      individuals having 4 (beta [SE]=1.83 [0.42], P<0.0001) or >=5 pain locations
      (beta [SE]=1.86 [0.36], P<0.0001). CONCLUSION: LBP, foot pain, and elbow pain are
      significantly associated with WOMAC knee pain score, as are a higher total number
      of pain locations. This may have implications for clinical trial planning.

PMID- 20799267
TI  - Challenges in assessing nanomaterial toxicology: a personal perspective.
AB  - Nanotechnology exploits the fact that nanoparticles exhibit unique
      physicochemical properties, which are distinct from fine-sized particles of the
      same composition. It follows that nanoparticles may also express distinct
      bioactivity and unique interactions with biological systems. Therefore, it is
      essential to assess the potential health risks of exposure to nanoparticles to
      allow development and implementation of prevention measures. Risk assessment
      requires data concerning hazard and exposure. Several challenges face the field
      of nanotoxicology in obtaining the necessary data for assessment of the
      bioactivity of nanoparticles. They include: (1) the vast number of nanoparticle
      types to be evaluated, (2) the need to use nanoparticle doses and structure sizes
      in cellular and animal test systems which are relevant to anticipated workplace
      exposures, and (3) artifactual in vitro results due to absorption of nutrients or
      assay indicator compounds from the culture media. This 'opinion' reviews the
      progress made in the field of nanotoxicology in recent years to overcome these
      challenges.

PMID- 20799268
TI  - Validated method for the quantification of atractylenolide III in different
      processed products of rhizoma Atractylodes Macrocephalae.
AB  - INTRODUCTION: Rhizoma Atractylodes Macrocephalae (RAM) contains several
      sesquiterpene compounds including atractylenolide III (AO-III). This bioactive
      compound may be used as a chemical marker for the quality control of different
      processed RAM products. OBJECTIVE: To develop and validate an RP-HPLC method for
      the quantitative determination of AO-III in RAM and in a variety of processed RAM
      products. METHODOLOGY: HPLC was carried out using a Kromssil C(18) RP-column
      eluted with methanol-water (70:30) at a flow rate of 1.0  mL/min and with UV
      detection at 220  nm. Full validation was performed using standard methods.
      RESULTS: The linear range of AO-III was 5-50  ug/mL; the regression equation was
      y = 10210x + 11194 (r = 0.9994) and the average recovery was 101.08% (RSD =
      0.98%). The detection and quantification limits for AO-III were determined to be
      0.005 and 0.018  ug/mL at signal-to-noise ratios of approximately 3:1 and 10:1,
      respectively. CONCLUSION: The described HPLC method is appropriate for quality
      assurance and differentiation of AO-III in RAM and different processed products.

PMID- 20799269
TI  - Enantiomeric differentiation of atropine/hyoscyamine by (13) C NMR spectroscopy
      and its application to Datura stramonium extract.
AB  - INTRODUCTION: The two enantiomers of hyoscyamine, an alkaloid found in many plant
      species, have distinct pharmacological and biological properties. Methods for the
      discrimination of both enantiomers are almost exclusively based on chiral
      HPLC/UV. Determination of the enantiomeric ratio (e.r.) of hyoscyamine is a
      challenging problem since this compound tends to racaemise, forming atropine
      during acid-base extraction. OBJECTIVE: To develop a protocol for the calculation
      of enantiomeric ratio of hyoscyamine in a plant extract using a (13) C NMR
      method. METHODOLOGY: Samples were prepared by extraction of dried Datura
      stramonium seeds. Observation of C12 and C15 NMR signals of hyoscyamine in the
      presence of one equivalent of TFA and sub-stoichiometric amount of Yb(hfc)(3)
      allowed the calculation of the e.r. of S-(-) and R-(+)-hyoscyamine.The method was
      optimised with various mixtures of (+) and (-)-hyoscyamine ranging from 50:50
      (racaemic mixture, i.e. atropine) to 98.5:1.5. The e.r. measured by NMR on the
      signals of aromatic C12 and C15 were in agreement with the gravimetrically
      prepared samples. The method was then applied to an extract of Datura stramonium
      and S-(-)-hyoscyamine was the unique enantiomer. CONCLUSION: The study showed
      that the e.r. determination of atropine/hyoscyamine was achieved with a routine
      NMR spectrometer, using CLSR/TFA on pure compounds as well as on the crude
      extract of Datura stramonium.

PMID- 20799270
TI  - Simultaneous analysis of diosgenin and sarsasapogenin in Asparagus officinalis
      byproduct by thin-layer chromatography.
AB  - INTRODUCTION: Asparagus officinalis L. has several biological activities
      including antifungal, antiviral and antitumoral activities due to the steroidal
      saponins. Normally diosgenin and sarsasapogenin are analysed separately by thin
      layer chromatography or high-performance liquid chromatography (HPLC-UV or HPLC
      ELSD), which is time-consuming and expensive, so we need to find a rapid solution
      to this problem. OBJECTIVE: To develop a sensitive, rapid and validated TLC
      method for simultaneous detection and quantification of diosgenin and
      sarsasapogenin. METHODOLOGY: Samples were prepared by extraction of A.
      officinalis with 70% aqueous ethanol to get steroidal saponins, and then
      hydrolysed using 36  mL 2 m hydrochloric acid for 3  h. The hydrolysis product
      was extracted with chloroform, and then analysed by TLC, the results of which
      were verified by HPLC and HPLC-MS. RESULTS: The retention factor (R(f)) of
      diosgenin and sarsasapogenin on TLC plate were 0.49 and 0.6, respectively. After
      calculation from the regression equation of the standard curve, the contents of
      diosgenin and sarsasapogenin in the A. officinalis extract were 0.27-0.46 and
      0.11-0.32%, respectively. CONCLUSION: The study showed that thin-layer
      chromatography can be applied for the determination of diosgenin and
      sarsasapogenin in the oldest tissue of A. officinalis, and also can be conducted
      for screening of sapogenin in other plant or extracts.

PMID- 20799271
TI  - Determination and comparative analysis of major iridoids in different parts and
      cultivation sources of Morinda citrifolia.
AB  - INTRODUCTION: Noni is a medicinal plant with a long history of use as a folk
      remedy in many tropical areas, and is attracting more attention worldwide. A
      comprehensive study on the major phytochemicals in different plant parts (fruit,
      leaf, seed, root and flower) and sources is of great value for fully
      understanding their diverse medicinal benefits. OBJECTIVE: To quantitatively
      determine the major iridoid components in different parts of noni plants, and
      compare iridoids in noni fruits collected from different tropical areas
      worldwide. METHODOLOGY: The optimal chromatographic conditions were achieved on a
      C(18) column with gradient elution using 0.1% formic acid aqueous formic acid and
      acetonitrile at 235  nm. The selective HPLC method was validated for precision,
      linearity, limit of detection, limit of quantitation and accuracy. RESULTS:
      Deacetylasperulosidic acid (DAA) was found to be the major iridoid in noni fruit.
      In order of predominance, DAA concentrations in different parts of the noni plant
      were dried noni fruit > fruit juice > seed > flower > leaf > root. The order of
      predominance for asperulosidic acid (AA) concentration was dried noni fruit >
      leaf > flower > root > fruit juice > seed. DAA and AA contents of methanolic
      extracts of noni fruits collected from different tropical regions were 13.8-42.9
      and 0.7-8.9  mg/g, respectively, with French Polynesia containing the highest
      total iridoids and the Dominican Republic containing the lowest. CONCLUSION:
      Iridoids DAA and AA are found to be present in leaf, root, seed and flower of
      noni plants, and were identified as the major components in noni fruit. Given the
      great variation of iridoid contents in noni fruit grown in different tropical
      areas worldwide, geographical factors appear to have significant effects on fruit
      composition. The iridoids in noni fruit were stable at the temperatures used
      during pasteurisation and, therefore, may be useful marker compounds for identity
      and quality testing of commercial noni products.

PMID- 20799272
TI  - Matrix solid-phase dispersion with sand in chromatographic analysis of essential
      oils in herbs.
AB  - INTRODUCTION: Matrix solid-phase dispersion (MSPD) is a very simple, cheap and
      relatively quick sample preparation procedure which involves simultaneous
      disruption and extraction of various solid and semi-solid samples due to the
      direct mechanical blending of the sample with a SPE sorbent, mainly C(18). Little
      is known about MSPD application as a sample preparation method for the analysis
      of essential oil components in herbs. OBJECTIVE: To evaluate if C(18) sorbent,
      commonly used in MSPD process, can be substituted with sand in the procedure of
      essential oil analysis. METHODOLOGY: Essential oil extracts were obtained from
      mint, sage, chamomile, marjoram, savory and oregano using MSPD with C(18) sorbent
      or sand, pressurised liquid extraction and steam distillation. Their qualitative
      and quantitative compositions ware established by GC-MS and GC-FID. RESULTS: The
      results prove that C(18) sorbent can be substituted with sand in the procedure of
      essential oil analysis in herbs. The recoveries of essential oil components
      estimated using MSPD/sand are almost equal to those using pressurised liquid
      extraction. CONCLUSION: The results presented in the paper reveal that MSPD with
      sand is suitable for the isolation of essential oil components from herbs. Its
      extraction efficiency is equivalent to pressurised liquid extraction, recognised
      as one of the most efficient extraction methods. The cost of MSPD procedure for
      essential oil analysis can be significantly diminished by substituting C(18) with
      sand.

PMID- 20799273
TI  - Development of chromatographic and free radical scavenging activity fingerprints
      by thin-layer chromatography for selected Salvia species.
AB  - INTRODUCTION: Plant-derived free radical scavengers have become the subject of
      intensive scientific interest. Recently, the concept of coupling chromatographic
      fingerprints with biological fingerprinting analysis has gained much attention
      for the quality control of plant extracts. However, identification of free
      radical scavenging activity of each single compound in a complex mixture is a
      difficult task. Thin-layer chromatography with post-chromatographic
      derivatisation with the methanol solution of DPPH can be a valuable tool in such
      analyses. OBJECTIVE: Development of chromatographic and free radical scavenging
      fingerprints of nineteen Salvia species grown and cultivated in Poland.
      METHODOLOGY: Chromatography was performed on the silica gel layers with use of
      two eluents, one for the resolution of the less polar compounds, and the other
      one for the resolution of the medium and highly polar ones. The plates were
      sprayed with the vanillin-sulfuric acid reagent to produce chemical fingerprints,
      and with DPPH solution to generate free radical scavenging fingerprints. RESULTS:
      With four Salvia species, it was revealed that their strong free radical
      scavenging properties are not only due to the presence of polar flavonoids and
      phenolic acids, but also due to the presence of several free radical scavengers
      in the less polar fraction. Because of the similarities in both the
      chromatographic and the free radical scavenging fingerprints, S. triloba can be
      introduced as a possible equivalent of the pharmacopoeial species, S.
      officinalis. CONCLUSION: Fingerprints developed in the experiments proved useful
      for the analysis of complex extracts of the different Salvia species.

PMID- 20799274
TI  - Systematic characterisation of secondary metabolites from Ixeris sonchifolia by
      the combined use of HPLC-TOFMS and HPLC-ITMS.
AB  - INTRODUCTION: Ixeris sonchifolia (Bunge) Hance, a folk medicine, has been widely
      used in China for its anti-inflammatory and haemostatic effects. However, the
      miscellaneous component composition of this herbal medicine is not well known.
      OBJECTIVE: To develop a fast and comprehensive analytical method for the
      characterisation of various components from I. Sonchifolia, as a tool for the
      quality control of the herb and its related preparations. METHODOLOGY: Ixeris
      sonchifolia samples were extracted with 60% aqueous methanol, purified by solid
      phase extraction and then analysed by the combinatorial use of HPLC-TOFMS and
      HPLC-ITMS. RESULTS: A total of six sesquiterpene lactones, six phenolic acids and
      seven flavonoids were identified or tentatively characterised. Five of them were
      reported for the first time in I. sonchifolia and, in particular, two amino acid
      sesquiterpene lactone conjugates, 11,13-dihydro-13-prolyl-ixerin Z and 11,13
      dihydro-13-prolyl-ixerin Z(1), that were first found in this plant source.
      CONCLUSION: A global profile of I. sonchifolia constituents was described, which
      could be useful for the quality control of this herb and its related
      preparations. The employed combination of HPLC-TOFMS and HPLC-ITMS could also be
      a promising tool for the analysis of other herbal medicines containing
      sesquiterpene lactones, phenolic acids or flavonoids.

PMID- 20799275
TI  - Analysis of marker compounds with anti-platelet aggregation effects in Mailuoning
      injection using platelet binding assay combined with HPLC-DAD-ESI-MS and solid
      phase extraction technique.
AB  - INTRODUCTION: Mailuoning is prepared from a traditional formula of Chinese
      medicines and widely used as an antithrombotic agent. In this study, the platelet
      binding assay was used as a novel biospecific separation and analysis method to
      explore its active constituents, which could be considered as marker compounds
      for quality control. OBJECTIVE: To establish a rapid and simple method to predict
      marker compounds in herbal medicine injection and evaluate the effects of those
      compounds. MATERIAL AND METHODS: Platelets were used to bind and separate
      constituents. Binding constituents were analysed and taken as potential active
      compounds for further evaluation. Solid-phase-extraction was adopted to improve
      sensitivity. HPLC-DAD and ESI-MS were used to determine the binding constituents.
      RESULTS: Five compounds were extracted through the platelet binding process and
      identified as neochlorogenic acid, caffeic acid, isochlorogenic acid and their
      isomers. Caffeic acid was selected for the flow cytometric assay to test its
      effect on platelets activation, which was determined by CD62P (P-selectin)
      expression. The results indicated that caffeic acid could significantly inhibit
      platelet activation while chlorogenic acid did not. CONCLUSION: Caffeic acid
      could be considered as a marker compound of Mailuoning injection due to its anti
      platelet effect. The study also suggested that platelet binding assay combined
      with some preconcentration technique could be efficiently used to predict anti
      platelet compounds in complicated herbal medicines.

PMID- 20799276
TI  - A comparison of alternative sample preparation procedures for the analysis of
      swainsonine using LC-MS/MS.
AB  - INTRODUCTION: Swainsonine, a polyhydroxy indolizidine alkaloid and known
      glycosidase inhibitor, is found in a number of different plants that cause a
      lysosomal storage disease known as locoism in the western USA. Most recently
      swainsonine has been analysed by LC-MS/MS after sample extraction and preparation
      from ion-exchange resins. OBJECTIVE: To compare previously published sample
      preparation procedures with several new alternative procedures to provide methods
      using either commercially available solid-phase extraction equipment or
      procedures which significantly reduce sample preparation time. METHODOLOGY: A
      previously reported and validated sample preparation method using ion-exchange
      resin was compared with methods using a commercially available solid-phase
      extraction cartridge, a solvent partitioning procedure or a single solvent
      extraction procedure using one of two solvents. Twenty different plant samples of
      varying swainsonine concentrations were prepared in triplicate and analysed by LC
      MS/MS. The measured concentration of swainsonine was then statistically compared
      between methods. RESULTS: There were no statistically significant differences
      found between four of the five different sample preparation methods tested.
      CONCLUSION: A commercially available SPE cartridge can be used to replace the
      previously used ion-exchange resin for swainsonine analysis. For very rapid
      analyses the SPE procedure can be eliminated and a simple, single solvent
      extraction step used for sample preparation.

PMID- 20799277
TI  - Determination of hydroxylated fatty acids from the biopolymer of tomato cutin and
      their fate during incubation in soil.
AB  - INTRODUCTION: The plant cuticle is a thin, predominantly lipid layer that covers
      all primary aerial surfaces of vascular plants. The monomeric building blocks of
      the cutin biopolymer are mainly omega-hydroxy fatty acids. OBJECTIVE: Analysis of
      omega-hydroxy fatty acids from cutin isolated from tomato fruits at different
      stages of decomposition in soil. Different derivatives and mass spectrometric
      techniques were used for peak identification and evaluation. METHODOLOGY:
      Preparation of purified cutin involving dewaxing and HCl treatment. Incubation of
      purified cutin for 20 months in soil. Pentafluorobenzoyl derivatives were used
      for GC/MS operated in the electron capture negative ion (ECNI) mode and
      trimethylsilyl ethers for GC/MS operated in the electron ionisation (EI) mode for
      analysis of omega-hydroxy fatty acids. RESULTS: Six omega-hydroxy fatty acids
      were detected in the purified cutin, three of which were identified as
      degradation products of 9,16-dihydroxyhexadecanoic acid as a consequence of the
      HCl treatment involved in the purification step. Incubation of the isolated cutin
      in soil was accompanied with decrease in concentration of all hydroxyl fatty
      acids. CONCLUSION: We produced evidence that the HCl treatment only affected free
      hydroxyl groups and thus could be used for proportioning free and bound OH-groups
      on cutin fatty acids. The method enabled a direct quantification of the omega
      hydroxy fatty acids throughout the incubation phase.

PMID- 20799278
TI  - Porcine tooth germ cell conditioned medium can induce odontogenic differentiation
      of human dental pulp stem cells.
AB  - It is suggested that the differentiation of tooth-derived stem cells is modulated
      by the local microenvironment in which they reside. Previous studies have
      indicated that tooth germ cell-conditioned medium (TGC-CM) holds the potential to
      induce dental pulp stem cells (DPSCs) to differentiate into the odontogenic
      lineage. Nevertheless, human TGC-CM (hTGC-CM) is not feasible in practical
      application, so we conjectured that xenogenic TGC-CM might exert a similar
      influence on human dental stem cells. In this study, we chose swine as the
      xenogenic origin and compared the effect of porcine tooth germ cell-conditioned
      medium (pTGC-CM) with its human counterpart on human DPSCs. Morphological
      appearance, colony-forming assay, in vitro multipotential ability, protein and
      gene expression of the odontogenic phenotype and the in vivo differentiation
      capacity of DPSCs were evaluated. The results showed that pTGC-CM exerted a
      similar effect to hTGC-CM in inducing human DPSCs to present odontogenic changes,
      which were indicated by remarkable morphological changes, higher multipotential
      capability and the expression of some odontogenic markers in gene and protein
      levels. Besides, the in vivo results showed that pTGC-CM-treated DPSCs, similar
      to hTGC-CM-treated DPSCs, could form a more regular dentine-pulp complex. Our
      data provided the first evidence that pTGC-CM is able to exert almost the same
      effect on DPSCs with hTGC-CM. The observations suggest that the application of
      xenogenic TGC-CM may facilitate generating bioengineered teeth from tooth-derived
      stem cells in future.

PMID- 20799279
TI  - Blood-derived human osteoclast resorption activity is impaired by Hyaluronan-CD44
      engagement via a p38-dependent mechanism.
AB  - The control of bone resorption is crucial in osteolytic diseases. Once attached
      to bone, osteoclasts (OCs) initiate the resorption process through the activation
      of a complex cascade of morphological and biochemical changes. Hyaluronan (HA),
      an extracellular glycosaminoglycan long non-branching polysaccharide, is
      expressed in bone matrices. Here we demonstrate that HA counter-balances the
      erosion activity of human mature OCs by significantly reducing their degradative
      potential. HA treatment of fully differentiated OCs derived from human peripheral
      blood monocytes inhibited migration on collagen as well as bone resorption. HA
      mediated effects were primarily due to TRAcP, MMP-9, and cathepsin K down
      regulation and to the increased levels of TIMP-1, a natural MMP-9 inhibitor.
      Binding of HA to mature OCs was entirely mediated by CD44: function-blocking anti
      CD44 antibodies fully abrogated HA effects, and the engagement of HA receptor
      caused a rapid de-phosphorylation of Ser325 in the CD44 cytoplasmic tail. The
      inhibitory action by HA was associated with a transient up-phosphorylation of
      Pyk2, a novel persistent phosphorylation of p38 and the down-regulation of NFATc1
      transcription factor. Our results provide a direct evidence for the involvement
      of CD44 in the HA-dependent regulation of OC activity and suggest a signaling
      pathway that could be unique in OC function inhibition.

PMID- 20799280
TI  - Arsenic trioxide induces apoptosis through JNK and ERK in human mesothelioma
      cells.
AB  - Malignant mesothelioma is an aggressive tumor of serosal surfaces, which is
      refractory to current treatment options. Arsenic trioxide (As2O3) is used
      clinically to treat acute promyelocytic leukemia, and also to inhibit
      proliferation of several solid tumors including hepatoma, esophageal, and gastric
      cancer in vitro. Here we found that As2O3 inhibited cell viability of a
      mesothelioma cell line, NCI-H2052. As2O3 induced apoptosis of NCI-H2052 cells,
      which was accompanied by activation of c-Jun NH2-terminal kinase (JNK)1/2,
      extracellular signal-regulated kinase (ERK)1/2, and caspase-3. zVAD-fmk, a broad
      spectrum caspase inhibitor, inhibited As2O3-induced apoptosis and activation of
      caspase-3, but not that of JNK1/2 and ERK1/2. Small interfering RNAs (siRNAs)
      targeting JNK1/2 suppressed As2O3-induced caspase-3 activation and apoptosis,
      indicating that JNK1/2 regulate As2O3-induced apoptosis though caspase cascade.
      Furthermore, JNK1 siRNA abrogated As2O3-induced JNK2 phosphorylation and JNK2
      siRNA abrogated As2O3-induced JNK1 phosphorylation, suggesting that JNK1 and JNK2
      interact with each other. Moreover, JNK1 siRNA, but not JNK2 siRNA, abrogated
      As2O3-induced ERK1/2 phosphorylation. JNK2 siRNA together with PD98059, a
      specific MAPK/ERK kinase inhibitor, suppressed As2O3-induced apoptosis more
      significantly than JNK2 siRNA alone. These results indicated that As2O3 induces
      apoptosis of NCI-H2052 cells mainly through JNK1/2 activation, and that ERK1/2 is
      involved in As2O3-induced apoptosis when JNK1/2 are inactivated.

PMID- 20799281
TI  - Complexity of polycomb group function: diverse mechanisms of target specificity.
AB  - Epigenetic regulation of gene expression has become relevant to nearly all areas
      of biomedical research. The emergence of technologies that allow for examination
      of the epigenome combined with identification of key protein complexes that
      mediate the myriad chromatin modifications that occur have greatly enhanced the
      versatility and efficacy of tools with which to study normal development and
      disease states. The evolutionarily conserved polycomb group genes (PcG) have been
      identified as a predominant mechanism by which gene silencing occurs during
      development, differentiation, and disease. While molecular events that target PcG
      complexes have been well defined in some non-vertebrate models, the details of
      locus specificity and functional diversity of mammalian PcG proteins have not yet
      unresolved. Here we discuss recent findings that offer novel mechanistic events
      and add complexity to our understanding of PcG function in vertebrates.

PMID- 20799282
TI  - Summary of the 9th annual meeting of the Italian Society for Virology.
AB  - The 9th annual meeting of the Italian Society for Virology (SIV) comprised seven
      plenary sessions focused on: General virology and viral genetics; Virus-Host
      interaction and pathogenesis; Viral oncology; Emerging viruses and zoonotic,
      foodborne, and environmental pathways of transmission; Viral immunology and
      vaccines; Medical virology and antiviral therapy; Viral biotechnologies and gene
      therapy. Moreover, four hot topics were discussed in special lectures: the
      Pioneer in human virology lecture regarding the control of viral epidemics with
      particular emphasis on the human immunodeficiency virus (HIV), the Pioneer in
      plant virology lecture focused on cell responses to plant virus infection, a
      Keynote lecture on the epidemiology and genetic diversity of Crimea-Congo
      Hemorrhagic Fever virus, and the G.B. Rossi lecture on the molecular basis and
      clinical implications of human cytomegalovirus tropism for endothelial/epithelial
      cells. The meeting had an attendance of about 160 virologists. A summary of the
      plenary lectures and oral selected presentations is reported.

PMID- 20799283
TI  - The evolution of volatile compounds profile of "Toscano" dry-cured ham during
      ripening as revealed by SPME-GC-MS approach.
AB  - The volatile compounds profile is an important feature for the characterization
      of dry-cured hams. Some minor typical Italian products, such as 'Toscano' ham,
      have been poorly studied in regards to their composition of volatile compounds.
      In this article, we studied the evolution of the aromatic profile of 'Toscano'
      dry-cured ham by solid-phase microextraction-gas chromatographic-mass
      spectrometry (SPME-GC-MS) with ripening. Ten right thighs were cured according to
      the 'Toscano' PDO protocol, sampled at 0, 1, 3, 6 and 12 months and submitted to
      volatile compounds analysis by SPME with a Divinylbenzene
      (DVB)/Carboxen/Polydimethylsiloxane (PDMS) 75-u Stable Flex fibre. An Agilent
      5975C mass selective detector (MSD) spectrometer with electron ionization (EI)
      source operating in scan mode within the m/z 29-350 range was used for data
      collection. Seven internal standards, either deuterium labeled or absent in the
      specimens and chosen to represent low or high boiling esters, alcohols, acids or
      phenols, were added to the homogenized samples and used to normalize the SPME
      fibre response to account for response changes upon wearing. Linear calibrations
      were obtained in this way for selected representative compounds. Over 60
      compounds belonging to esters, aldehydes, organic acids, ketones and alcohols
      were identified by comparison with spectral libraries and Kovats indices.
      Aldehydes were the most represented chemical family, followed by organic acids,
      alcohols, ketones and esters. The aldehydes and ketones increased during the
      first 3 months, when the larger formation of volatiles occurred. For other
      families, the evolution over time was less evident. The principal component and
      discriminant analyses of the aromatic profile were effective in classifying the
      hams at 0, 6 or 12 months of ripening while for 1 and 3 months' samples a partial
      overlapping was shown. These results represent the first characterization of
      'Toscano' ham and may constitute the basis to identify the best ripening time and
      define an analytical quality standard for this typical ham.

PMID- 20799284
TI  - Multivariate one-sided multiple comparison procedure with a control based on the
      approximate likelihood ratio test.
AB  - In this study, we discuss a multiple comparison procedure with a control for
      multivariate one-sided test in each pairwise comparison. For pairwise
      comparisons, we use the approximate likelihood ratio test statistics derived by
      Tang et al. (An approximate likelihood ratio test for a normal mean vector with
      nonnegative components with application to clinical trials. Biometrika 1989, 76,
      577-583). We derive a formula to determine the critical value for pairwise
      comparisons satisfying a specified significance level. Furthermore, we formulate
      the power of the test for our multiple comparison procedure. Finally, we give
      some numerical examples regarding the critical values and the power of the test.

PMID- 20799285
TI  - Impulsive rats are less maternal.
AB  - Early life environment and maternal care can have long-lasting effects on
      behavior and physiology. Previously, we found that compared to mother-reared (MR)
      female rats, rats reared without mothers, siblings, and nest, through
      artificially rearing (AR), show reduced levels of maternal behavior when they
      grow up. These effects can be reversed if AR pups are provided with extra
      "licking-like" tactile stimulation during the preweaning period [Gonzalez et al.
      [2001] Developmental Psychobiology, 38(1), 11-42]. We also found that AR rats are
      more action impulsive and have reduced attentional capacities in comparison to
      their MR siblings [Lovic, Fletcher, & Fleming, in preparation; Lovic & Fleming
      [2004] Behavioural Brain Research 148: 209-219]. However, it is unknown whether
      increased impulsivity contributes to reduced levels of maternal behaviors. The
      purpose of this study was to assess the relationship between impulsivity and
      maternal behavior in AR and MR rats. Female rats were reared with (MR) or without
      mothers (AR) and half of the AR rats received additional stroking stimulation. As
      adults, AR and MR rats were mated and maternal behavior towards their own pups
      was assessed. In addition, rats were assessed on impulsive action (differential
      reinforcement of low-rate schedule; DRL-20s). Consistent with previous findings,
      AR rats were both less maternal and more action impulsive than MR rats. Partial
      correlations revealed that impulsivity was inversely related to pup licking
      impulsive rats were less maternal.

PMID- 20799286
TI  - Randomized clinical trial of the influence of mechanical bowel preparation on
      faecal microflora in patients undergoing colonic cancer resection.
AB  - BACKGROUND: This study investigated the influence of mechanical bowel preparation
      (MBP) on faecal microflora, using rRNA-targeted reverse transcription
      quantitative polymerase chain reaction in patients undergoing colonic cancer
      resection. METHODS: Forty-two patients undergoing elective colonic surgery were
      randomized into MBP or no-MBP groups (21 in each group). The main outcome was the
      bacterial microflora and faecal organic acid content of faecal material obtained
      at operation. RESULTS: Clinical characteristics were similar in the two groups.
      Bowel content in the resected specimens did not differ significantly. The count
      of bacterial microflora, such as Bifidobacterium and total Lactobacillus, in both
      intraoperative faecal material and first material after surgery was significantly
      lower in the MBP group than the no-MBP group (P < 0.050). Levels of faecal
      organic acids, such as acetic acid, propionic acid and butyric acid, in
      intraoperative faecal material were significantly lower, and levels of lactic
      acid were significantly higher, in the MBP group than in the no-MBP group (P <
      0.050). The succinic acid level was significantly higher after surgery than
      before operation in the MBP group (P = 0.008). CONCLUSION: Preoperative MBP
      caused an imbalance in the bowel microflora, suggesting that it offers no
      advantages in terms of enterobacterial microflora for patients undergoing colonic
      cancer resection. REGISTRATION NUMBER: UMIN000003153
      (http://www.umin.ac.jp/ctr/index.htm).

PMID- 20799287
TI  - Prostate cancer risk and exposure to pesticides in British Columbia farmers.
AB  - BACKGROUND: Several epidemiologic studies have reported an increased risk of
      prostate cancer among farmers. Our aim was to assess the risk of developing
      prostate cancer in relation to exposure to specific active compounds in
      pesticides. METHOD: A case-control approach was used with 1,516 prostate cancer
      patients and 4,994 age-matched internal controls consisting of all other cancer
      sites excluding lung cancer and cancers of unknown primary site. Lifetime
      occupational history was obtained through a self-administered questionnaire and
      used in conjunction with a job exposure matrix to estimate the participants'
      lifetime cumulative exposure to approximately 180 active compounds in pesticides.
      Conditional logistic regression was used to assess prostate cancer risk,
      adjusting for potential confounding variables and effect modifiers. These include
      age, ethnicity, alcohol consumption, smoking, education, and proxy respondent.
      RESULTS AND CONCLUSIONS: The significant association between prostate cancer risk
      and exposure to DDT (OR = 1.68; 95% CI: 1.04-2.70 for high exposure), simazine
      (OR = 1.89; 95% CI: 1.08-3.33 for high exposure), and lindane (OR = 2.02; 95% CI:
      1.15-3.55 for high exposure) is in keeping with those previously reported in the
      literature. We also observed a significant excess risk for several active
      ingredients that have not been previously reported in the literature such as
      dichlone, dinoseb amine, malathion, endosulfan, 2,4-D, 2,4-DB, and carbaryl. Some
      findings in our study were not consistent with those reported in the literature,
      including captan, dicamba, and diazinon. It is possible that these findings
      showed a real association and the inconsistencies reflected differences of
      characteristics between study populations.

PMID- 20799288
TI  - New anatomical classification of the axilla with implications for sentinel node
      biopsy.
AB  - BACKGROUND: The exact anatomical location of the sentinel lymph node (SLN) in the
      axilla has not ascertained clinically, but could be useful both for teaching
      purposes and to reduce the morbidity of SLN biopsy. The aim of the study was to
      determine the position of the SLN in the axilla and to demonstrate that this
      location is not random. METHODS: A consecutive series of 242 patients with stage
      I breast cancer (T1/T2 N0) or ductal carcinoma in situ who underwent SLN
      localization by peritumoral injection were included in a prospective study to map
      the location of the SLN in the axilla. A new anatomical classification of the
      lower part of the axilla based on the intersection of two anatomical landmarks,
      the lateral thoracic vein (LTV) and the second intercostobrachial nerve (ICBN),
      is described. These two constant elements form the basis of four axillary zones
      (A, B, C and D). RESULTS: In 98.2 per cent of patients the axillary SLN was
      located medially, alongside the LTV, either below the second ICBN (zone A, 86.8
      per cent) or above it (zone B, 11.5 per cent). In only four patients (1.8 per
      cent) was the SLN located laterally in the axilla. CONCLUSION: Regardless of the
      site of the tumour in the breast, 98.2 per cent of SLNs were found in the medial
      part of the axilla, alongside the LTV. This information should help to avoid
      unnecessary lateral dissections.

PMID- 20799289
TI  - Intraoperative ultrasonographic detection of communicating veins between adjacent
      hepatic veins during hepatectomy for tumours at the hepatocaval confluence.
AB  - BACKGROUND: The presence of communicating veins between adjacent hepatic veins
      may allow parenchyma-sparing hepatectomy. Taking advantage of improvements in
      ultrasound technology, such as e-flow modality, a study of the presence of
      communicating veins was conducted in patients with hepatic tumours at the caval
      confluence. METHODS: Consecutive patients undergoing surgery between October 2007
      and December 2009 for hepatic tumours in contact with or invading a hepatic vein
      at its caval confluence were included. Communicating vein mapping by means of e
      flow intraoperative ultrasonography (EF-IOUS) was carried out. RESULTS: A total
      of 20 patients were enrolled. Communicating veins between adjacent hepatic veins
      or with the inferior vena cava were detected in 16 patients. The median number of
      communicating veins was 1 (range 0-5). The total number of lesions removed was
      126 (range 1-46). In 11 of 12 patients requiring resection of a hepatic vein,
      communicating veins enabled a parenchyma-sparing procedure to be performed. No
      patient had a formal major hepatectomy. There was no postoperative mortality or
      major morbidity. CONCLUSION: EF-IOUS estimation of the frequency of communicating
      veins between adjacent hepatic veins suggests that such veins are common. This
      may facilitate parenchyma-sparing procedures in patients with hepatic tumours
      encroaching on major hepatic veins.

PMID- 20799290
TI  - Role of ultrasonography in the diagnosis of temporal arteritis.
AB  - BACKGROUND: Temporal artery (TA) biopsy is the current standard for diagnosing
      temporal arteritis, but has limited sensitivity. Colour duplex ultrasonography is
      a newer, non-invasive method of diagnosing temporal arteritis. METHODS: A
      systematic review was performed of trials comparing TA biopsy with duplex
      ultrasonography. Duplex results (halo sign, stenosis or vessel occlusion) were
      compared with either TA biospy findings or the American College of Rheumatology
      research criteria for diagnosing temporal arteritis. Trials were identified from
      MEDLINE, Embase and the Cochrane Library trials register. The performance of
      duplex ultrasonography was assessed with weighted independent sensitivity and
      specificity values, and summary receiver operating characteristic curve analysis.
      RESULTS: There were 17 eligible studies containing 998 patients. When the halo
      sign on duplex imaging was compared with TA biopsy, the sensitivity was 75 (95
      per cent confidence interval 67 to 82) per cent and the specificity was 83 (78 to
      88) per cent. There was no heterogeneity across the eligible studies. CONCLUSION:
      Duplex ultrasonography was relatively accurate for diagnosing temporal arteritis.
      It should become the first-line investigation, with biopsy reserved for patients
      with a negative scan.

PMID- 20799291
TI  - New concepts and applications in the macromolecular chemistry of fullerenes.
AB  - A new classification on the different types of fullerene-containing polymers is
      presented according to their different properties and applications they exhibit
      in a variety of fields. Because of their interest and novelty, water-soluble and
      biodegradable C(60)-polymers are discussed first, followed by polyfullerene-based
      membranes where unprecedented supramolecular structures are presented. Next are
      compounds that involve hybrid materials formed from fullerenes and other
      components such as silica, DNA, and carbon nanotubes (CNTs) where the most recent
      advances have been achieved. A most relevant topic is still that of C(60)-based
      donor-acceptor (D-A) polymers. Since their application in photovoltaics D-A
      polymers are among the most realistic applications of fullerenes in the so-called
      molecular electronics. The most relevant aspects in these covalently connected
      fullerene/polymer hybrids as well as new concepts to improve energy conversion
      efficiencies are presented.The last topics disccused relate to supramolecular
      aspects that are in involved in C(60)-polymer systems and in the self-assembly of
      C(60)-macromolecular structures, which open a new scenario for organizing, by
      means of non-covalent interactions, new supramolecular structures at the nano-
      and micrometric scale, in which the combination of the hydrofobicity of
      fullerenes with the versatility of the noncovalent chemistry afford new and
      spectacular superstructures.

PMID- 20799292
TI  - Carbon nanotubes: measuring dispersion and length.
AB  - Advanced technological uses of single-walled carbon nanotubes (SWCNTs) rely on
      the production of single length and chirality populations that are currently only
      available through liquid-phase post processing. The foundation of all of these
      processing steps is the attainment of individualized nanotube dispersions in
      solution. An understanding of the colloidal properties of the dispersed SWCNTs
      can then be used to design appropriate conditions for separations. In many
      instances nanotube size, particularly length, is especially active in determining
      the properties achievable in a given population, and, thus, there is a critical
      need for measurement technologies for both length distribution and effective
      separation techniques. In this Progress Report, the current state of the art for
      measuring dispersion and length populations, including separations, is
      documented, and examples are used to demonstrate the desirability of addressing
      these parameters.

PMID- 20799293
TI  - Interfacial rheology through microfluidics.
AB  - The bulk properties and structural characteristics of emulsions arise
      substantially from their interfacial rheology, which depends strongly on
      surfactant mass transfer and its coupling to flow. Typical methods used to
      measure such properties often employ simpler flows and larger drops than those
      encountered in typical processing applications. Mass transfer mechanisms are
      governed by droplet size; therefore experimentation at length scales typical of
      those encountered in applications is desired. Utilizing a microfluidic approach
      allows high-throughput experimentation at relevant length scales and with
      adjustable flow dynamics. Using a microfluidic device that facilitates the
      measurement of interfacial tension in two-phase droplet flows, particle tracers
      are also used to determine the droplet internal circulation velocity as a measure
      of interfacial mobility. Combining these measurements in a single device, the
      coupling between interfacial tension, interfacial retardation, and surfactant
      mass transfer is explored and mass transfer coefficients and interfacial mobility
      are measured for a two-phase system containing a diffusing surfactant. Such a
      device is also used to probe the deformability of elastic capsules and
      viscoelastic biological cells.

PMID- 20799294
TI  - Management of blunt injuries to the spleen.
AB  - BACKGROUND: Non-operative management (NOM) of blunt splenic injuries is nowadays
      considered the standard treatment. The present study identified selection
      criteria for primary operative management (OM) and planned NOM. METHODS: All
      adult patients with blunt splenic injuries treated at Berne University Hospital,
      Switzerland, between 2000 and 2008 were reviewed. RESULTS: There were 206
      patients (146 men) with a mean(s.d.) age of 38.2(19.1) years and an Injury
      Severity Score of 30.9(11.6). The American Association for the Surgery of Trauma
      classification of the splenic injury was grade 1 in 43 patients (20.9 per cent),
      grade 2 in 52 (25.2 per cent), grade 3 in 60 (29.1 per cent), grade 4 in 42 (20.4
      per cent) and grade 5 in nine (4.4 per cent). Forty-seven patients (22.8 per
      cent) required immediate surgery. Transfusion of at least 5 units of red cells
      (odds ratio (OR) 13.72, 95 per cent confidence interval 5.08 to 37.01), Glasgow
      Coma Scale score below 11 (OR 9.88, 1.77 to 55.16) and age 55 years or more (OR
      3.29, 1.07 to 10.08) were associated with primary OM. The rate of primary OM
      decreased from 33.3 to 11.9 per cent after the introduction of transcatheter
      arterial embolization in 2005. Overall, 159 patients (77.2 per cent) qualified
      for NOM, which was successful in 143 (89.9 per cent). The splenic salvage rate
      was 69.4 per cent. In multivariable analysis age at least 40 years was the only
      factor independently related to failure of NOM (OR 13.58, 2.76 to 66.71).
      CONCLUSION: NOM of blunt splenic injuries has a low failure rate. Advanced age is
      independently associated with an increased failure rate.

PMID- 20799295
TI  - Percutaneous transhepatic biliary drainage catheter tract recurrence in
      cholangiocarcinoma.
AB  - BACKGROUND: The aim of the study was to clarify the incidence, risk factors and
      treatment of percutaneous transhepatic biliary drainage (PTBD) catheter tract
      recurrence in patients with resected cholangiocarcinoma. METHODS: The medical
      records of 445 patients with perihilar and distal cholangiocarcinoma who
      underwent resection following PTBD were reviewed retrospectively. RESULTS: PTBD
      catheter tract recurrence was detected in 23 patients (5.2 per cent). The
      mean(s.d.) interval between surgery and onset of the recurrence was 14.4(13.8)
      months. On multivariable analysis, duration of PTBD (60 days or more), multiple
      PTBD catheters and macroscopic papillary tumour type were identified as
      independent risk factors. In four patients with synchronous metastasis, the PTBD
      sinus tract was resected simultaneously, at the time of initial surgery. Of 19
      patients with metachronous metastasis, 15 underwent surgical resection of the
      metastasis. Survival of the 23 patients with PTBD catheter tract recurrence was
      poorer than that of the 422 patients without recurrence (median 22.8 versus 27.3
      months; P = 0.095). Even after surgical resection of PTBD catheter tract
      recurrence, survival was poor. CONCLUSION: PTBD catheter tract recurrence is not
      unusual. The prognosis for these patients is generally poor, even after
      resection. To prevent this troublesome complication, endoscopic biliary drainage
      is first recommended when drainage is indicated.

PMID- 20799297
TI  - Enzymatic production of beta-D-glucose-1-phosphate from trehalose.
AB  - beta-D-Glucose-1-phosphate (betaGlc1P) is an efficient glucosyl donor for both
      enzymatic and chemical glycosylation reactions but is currently very costly and
      not available in large amounts. This article provides an efficient production
      method of betaGlc1P from trehalose and phosphate using the thermostable trehalose
      phosphorylase from Thermoanaerobacter brockii. At the process temperature of 60 
      degrees C, Escherichia coli expression host cells are lysed and cell treatment
      prior to the reaction is, therefore, not required. In this way, the theoretical
      maximum yield of 26% could be easily achieved. Two different purification
      strategies have been compared, anion exchange chromatography or carbohydrate
      removal by treatment with trehalase and yeast, followed by chemical phosphate
      precipitation. In a next step, betaGlc1P was precipitated with ethanol but this
      did not induce crystallization, in contrast to what is observed with other
      glycosylphosphates. After conversion of the product to its cyclohexylammonium
      salt, however, crystals could be readily obtained. Although both purification
      methods were quantitative (>99% recovery), a large amount of product (50%) was
      lost during crystallization. Nevertheless, a production process for crystalline
      betaGlc1P is now available from the cheap substrates trehalose and inorganic
      phosphate.

PMID- 20799296
TI  - Randomized clinical trial comparing inflammatory and angiogenic response after
      open versus laparoscopic curative resection for colonic cancer.
AB  - BACKGROUND: Several studies have suggested that laparoscopy might confer an
      oncological advantage in patients undergoing surgery for colonic cancer. A
      decreased inflammatory and angiogenic response has been proposed. This study
      compared the local and systemic inflammatory and angiogenic responses after open
      and laparoscopic surgery for colonic cancer. METHODS: Some 122 patients with
      colonic cancer were randomized to open or laparoscopic colectomy. Levels of
      interleukin (IL) 6 and vascular endothelial growth factor (VEGF) were measured in
      serum and peritoneal fluid at baseline, then at 4, 12, 24 and 48 h and on day 4
      after surgery. Samples obtained on day 4 were tested in an in vitro angiogenesis
      assay, with measurement of number of capillaries per field and capillary length.
      RESULTS: The serum IL-6 level was lower in the laparoscopic group at 4 h
      (mean(s.d.) 124(110) versus 244(326) pg/dl after open colectomy; P = 0.027). The
      serum VEGF concentration was also lower in the laparoscopic group at 48 h and day
      4 (430(435) versus 650(686) pg/dl; P = 0.001). Overall, local IL-6 and VEGF
      levels were significantly higher than serum levels but there were no differences
      between groups. In vitro, postoperative serum and peritoneal fluid samples were
      potently angiogenic but there were no differences between open surgery and
      laparoscopy. Rates of tumour recurrence and survival were similar in the two
      groups. CONCLUSION: Despite differences in postoperative serum levels of IL-6 and
      VEGF after open and laparoscopic surgery in patients with colonic cancer, the
      angiogenic response is comparable in both surgical approaches. REGISTRATION
      NUMBER: ISRCTN55624793 (http://www.controlled-trials.com).

PMID- 20799299
TI  - "On-water," microwave-assisted, Pd-catalyzed synthesis of indoles from imines and
      o-difunctionalized arenes.
AB  - Regioselectively substituted indoles are prepared by a Pd-catalyzed C-C/C-N bond
      forming sequence from imines and o-dihaloarenes or o-haloarene sulfonates. The
      heterogeneous reaction as a suspension in water and under microwave heating
      offers important advantages in comparison with the conventional reaction in an
      organic solvent, among them, operational simplicity, the employment of KOH
      solutions instead of alkoxides, and a dramatic reduction of reaction times.

PMID- 20799300
TI  - A tetranuclear-zinc-cluster-catalyzed practical and versatile deprotection of
      acetates and benzoates.
AB  - A new catalytic deacylation of acetates and benzoates through transesterification
      with methanol was developed (see scheme). Reactions with various acid- and
      nucleophile-sensitive functional groups proceeded efficiently in the presence of
      a catalytic amount of the tetranuclear zinc cluster. The present catalysis is
      applicable to less-reactive tertiary acetates, the deacylation of which is
      difficult to achieve by transesterification with other catalysts.

PMID- 20799301
TI  - Insulator base pairs for lighting-up perylenediimide in a DNA duplex.
AB  - Quenched: Perylenediimide (PDI) is highly quenched by nucleobases, which greatly
      restricts its application as a fluorescent probe. Here, we propose "insulator
      base pairs" tethering cyclohexane ring through D-threoninol. When "insulator base
      pairs" were inserted between PDI and nucleobases, the quantum yield of PDI
      drastically increased several thousand-fold. The "insulator base pairs" reported
      here also have the potential to increase the quantum yields of other
      fluorophores.

PMID- 20799302
TI  - Formation of surface traps on quantum dots by bidentate chelation and their
      application in low-potential electrochemiluminescent biosensing.
AB  - Bidentate chelation, meso-2,3-dimercaptosuccinic acid (DMSA), was used as a
      stabilizer for the synthesis of CdTe quantum dots (QDs). The bidentate chelate
      QDs, characterized with FT-IR, PL, and UV/Vis spectroscopy; element analysis; and
      high-resolution transmission electron microscope, exhibited surface traps due to
      the large surface/volume ratio of QD particle and the steric hindrance of the
      DMSA molecule. The unpassivated surface of the QDs produced a narrower band gap
      than the core and electrochemiluminescent (ECL) emission at relatively low
      cathodic potential. In air-saturated pH 7.0 buffer, the QDs immobilized on
      electrode surface showed an intense ECL emission peak at -0.85 V (vs. Ag/AgCl).
      H(2)O(2) produced from electrochemical reduction of dissolved oxygen was
      demonstrated to be the co-reactant, which avoided the need of strong oxidant as
      the co-reactant and produced a sensitive analytical method for peroxidase-related
      analytes. Using hydroquinone/horseradish peroxidase/H(2)O(2) as a model system, a
      new, reagentless, phenolic, ECL biosensor for hydroquinone was constructed, based
      on the quenching effect of ECL emission of QDs by consumption of co-reactant
      H(2)O(2). The biosensor showed a linear range of 0.2-10 MUM with acceptable
      stability and reproducibility. This work opens new avenues in the search for new
      ECL emitters with excellent analytical performance and makes QDs a more
      attractive alternative in biosensing.

PMID- 20799304
TI  - Sexithiophene encapsulated in a single-walled carbon nanotube: an in situ Raman
      spectroelectrochemical study of a peapod structure.
AB  - The interaction of single-walled carbon nanotubes (SWCNTs) and alpha
      sexithiophene (6T) was studied by Raman spectroscopy and by in situ Raman
      spectroelectrochemistry. The encapsulation of 6T in SWCNT and its interaction
      causes a bleaching of its photoluminescence, and also small shifts of its Raman
      bands. The Raman features of the SWCNT with embedded 6T (6T-peapods) change in
      both intensity and frequency compared to those of pristine SWCNT, which is a
      consequence of a change of the resonant condition. Electrochemical doping
      demonstrated that the electrode potential applied to the SWCNT wall causes
      changes in the embedded 6T. The effects of electrochemical charging on the Raman
      features of pristine SWCNT and 6T@SWCNT were compared. It is shown that the
      interaction of SWCNT with 6T also changes the electronic structure of SWCNT in
      its charged state. This change of electronic structure is demonstrated both for
      semiconducting and metallic tubes.

PMID- 20799305
TI  - Glycosidic prodrugs of highly potent bifunctional duocarmycin derivatives for
      selective treatment of cancer.

PMID- 20799306
TI  - Dynamic peptides as biomimetic carbohydrate receptors.

PMID- 20799307
TI  - An organocatalytic, delta-regioselective, and highly enantioselective
      nucleophilic substitution of cyclic Morita-Baylis-Hillman alcohols with indoles.

PMID- 20799308
TI  - Photoswitchable nanoassemblies by electrostatic self-assembly.

PMID- 20799309
TI  - Asymmetric cyclopropanation of alkenes with dimethyl diazomalonate catalyzed by
      chiral diene-rhodium complexes.

PMID- 20799310
TI  - Catalyst-controlled Wacker-type oxidation of protected allylic amines.

PMID- 20799313
TI  - Photochemical incorporation of diphosphorus units into organic molecules.

PMID- 20799311
TI  - alpha-ketoheterocycles as inhibitors of Leishmania mexicana cysteine protease
      CPB.
AB  - Cysteine proteases of the papain superfamily are present in nearly all eukaryotes
      and also play pivotal roles in the biology of parasites. Inhibition of cysteine
      proteases is emerging as an important strategy to combat parasitic diseases such
      as sleeping sickness, Chagas disease, and leishmaniasis. Inspired by the in vivo
      antiparasitic activity of the vinylsulfone-based cysteine protease inhibitors, a
      series of alpha-ketoheterocycles were developed as reversible inhibitors of a
      recombinant L. mexicana cysteine protease, CPB2.8. Three isoxazoles and
      especially one oxadiazole compound are potent reversible inhibitors of CPB2.8;
      however, in vitro whole-organism screening against a panel of protozoan parasites
      did not fully correlate with the observed inhibition of the cysteine protease.

PMID- 20799315
TI  - Divergent heparin-induced fibrillation pathways of a prion amyloidogenic
      determinant.
AB  - Polysaccharides and glycosaminoglycans (GAGs), particularly heparin, have been
      shown to directly affect fibrillation phenomena and the biological activities of
      amyloid proteins. We present a systematic analysis of the impact of heparin upon
      fibrillation of the amyloidogenic determinant of the prion protein PrP(106-126).
      Experimental data, including thioflavin T fluorescence, transmission electron
      microscopy, and circular dichroism, demonstrate that heparin induced dramatically
      diverging aggregation pathways of PrP(106-126). Specifically, enhanced beta-sheet
      formation of the prion fragment leading to fibril assemblies occurred in
      solutions containing low heparin/prion mole ratios, while mixtures containing a
      greater abundance of heparin showed almost complete inhibition of PrP(106-126)
      fibril formation. Based upon the experimental data we have proposed a unified
      model accounting for the interplay between the roles of heparin as a scaffold for
      nucleation and fibril growth on the one hand and as a disruptor of fibrillation
      through electrostatic affinity with the monomeric peptide units on the other.
      This study clarifies previous conflicting studies, and concludes that GAGs
      inhibit fibrillation and amyloid toxicity in some cases, and promote
      amyloidogenesis in others.

PMID- 20799316
TI  - Dealloying to nanoporous silver and its implementation as a template material for
      construction of nanotubular mesoporous bimetallic nanostructures.
AB  - Nanoporous silver (NPS) is fabricated by selectively dissolving Al from AgAl
      alloys in corrosive electrolytes at room temperature. Electron spectroscopy
      characterizations demonstrate that the NaOH electrolyte is beneficial to the
      formation of a three-dimensional bicontinuous porous nanostructure with uniform
      and tunable pore and ligament dimensions of a few tens of nanometers, while
      processing in HCl electrolyte easily lead to coarsened porous nanostructures. The
      high-surface-area Ag nanostructures are demonstrated as novel effective template
      materials to the construction of nanotubular mesoporous Pt/Ag and Pd/Ag alloy
      structures, which are realized via room temperature galvanic replacement
      reactions with H(2)PtCl(6) and K(2)PdCl(4) solutions by adding a high
      concentration of Cl(-) ions as a coordinating agent. Electrochemical measurements
      indicate that the resulting hollow and porous bimetallic nanostructures show
      enhanced electrocatalytic activities and CO-tolerance with better durability
      toward methanol and formic acid oxidation due to alloying with Ag.

PMID- 20799317
TI  - An integrated catalytic approach to fermentable sugars from cellulose.

PMID- 20799318
TI  - Somatic mosaicism in Menkes disease suggests choroid plexus-mediated copper
      transport to the developing brain.
AB  - The primary mechanism of copper transport to the brain is unknown, although this
      process is drastically impaired in Menkes disease, an X-linked neurodevelopmental
      disorder caused by mutations in an evolutionarily conserved copper transporter,
      ATP7A. Potential central nervous system entry routes for copper include brain
      capillary endothelial cells that originate from mesodermal angioblasts and form
      the blood-brain barrier, and the choroid plexuses, which derive from embryonic
      ectoderm, and form the blood-cerebrospinal fluid barrier. We exploited a rare
      (and first reported) example of somatic mosaicism for an ATP7A mutation to shed
      light on questions about copper transport into the developing brain. In a 20
      month-old Menkes disease patient evaluated before copper treatment, blood copper,
      and catecholamine concentrations were normal, whereas levels in cerebrospinal
      fluid were abnormal and consistent with his neurologically severe phenotype. We
      documented disparate levels of mosaicism for an ATP7A missense mutation, P1001L,
      in tissues derived from different embryonic origins; allele quantitation showed
      P1001L in approximately 27% of DNA samples from blood cells (mesoderm-derived)
      and 88% from cultured fibroblasts (ectoderm-derived). These findings imply that
      the P1001L mutation in the patient preceded formation of the three primary
      embryonic lineages at gastrulation, with the ectoderm layer ultimately harboring
      a higher percentage of mutation-bearing cells than mesoderm or endoderm. Since
      choroid plexus epithelia are derived from neuroectoderm, and brain capillary
      endothelial cells from mesodermal angioblasts, the clinical and biochemical
      findings in this infant support a critical role for the blood-CSF barrier
      (choroid plexus epithelia) in copper entry to the developing brain.

PMID- 20799320
TI  - Further characterization of microdeletion syndrome involving 2p15-p16.1.
AB  - We report on a patient presenting with cognitive delay, prenatal and postnatal
      growth deficiency, microcephaly, ptosis of eyelids, high and broad nasal root,
      and camptodactyly. Analysis of a dense whole genome single-nucleotide
      polymorphism (SNP) array showed a de novo 3.35 Mb deletion on 2p15-p16.1. In
      order to study the parental origin of the deletion we analyzed selected SNPs in
      the deleted area in the proband and her parents showing Mendelian
      incompatibilities suggesting a de novo deletion on the chromosome of paternal
      origin. Based on the five cases described previously in the literature, we have
      narrowed the critical region responsible for the 2p15-p16.1 microdeletion
      syndrome phenotype. The critical region does not include the VRK2 gene that had
      been speculated to have a role in cortical dysplasia. However, the association of
      the VRK2 gene with cortical dysplasia remains to be determined, as MRI imaging of
      the brain and gene content of the 2p15-16 deletion becomes established in more
      patients.

PMID- 20799319
TI  - Recurrence risk for offspring of twins discordant for oral cleft: a population
      based cohort study of the Danish 1936-2004 cleft twin cohort.
AB  - Our objective in this Danish population-based cohort study was to estimate the
      recurrence risk of isolated oral cleft (OC) for offspring of the unaffected co
      twins of OC discordant twin pairs and to compare this risk to the recurrence risk
      in the offspring of the affected co-twin as well as to the risk in the background
      population. During 1936-2004, 207 twin pairs were ascertained, among whom at
      least one twin had an OC. The index persons were twins discordant for OC who had
      children (N=117), and their offspring (N=239). The participants were ascertained
      by linkage between The Danish Facial Cleft Database, The Danish Twin Registry and
      The Danish Civil Registration System. In the study OC recurrence risk for
      offspring of the affected and unaffected twin and relative risk were compared to
      the background prevalence. We found that among 110 children of the 54 OC affected
      twins, two (1.8%) children had OC corresponding to a significantly increased
      relative risk (RR=10; 95% CI 1.2-35) when compared to the frequency in the
      background population. Among the 129 children of the 63 unaffected twins, three
      (2.3%) children were affected, corresponding to a significantly increased
      relative risk (RR=13; 95% CI 2.6-36) when compared the background prevalence. We
      concluded that in OC discordant twin pairs similar increased recurrence risks
      were found among offspring of both OC affected and OC unaffected twins. This
      provides further evidence for a genetic component in cleft etiology and is useful
      information for genetic counseling of twin pairs discordant for clefting.

PMID- 20799321
TI  - Molecular characterization of a new patient with a non-recurrent inv dup del 2q
      and review of the mechanisms for this rearrangement.
AB  - We report on newborn baby with microcephaly, facial anomalies, congenital heart
      defects, hypotonia, wrist contractures, long fingers, adducted thumbs, and club
      feet. Cytogenetic studies revealed an inverted duplication with terminal deletion
      (inv dup del) of 2q in the patient and a paternal 2qter deletion polymorphism.
      Microsatellite markers demonstrated that the inv dup del was maternal in origin
      and intrachromosomal. Intra or interchromosomal rearrangements may cause this
      aberration either by a U-type exchange (end-to-end fusion), an unequal crossover
      between inverted repeats (non-allelic homologous recombination: NAHR), or through
      breakage-fusion-bridge (BFB) cycles leading to a sister chromatid fusion by non
      homologous end joining (NHEJ). A high-resolution oligo array-CGH (244 K) defined
      the breakpoints and did not detect a single copy region with a size exceeding
      12.93 Kb in the fusion site. The size of the duplicated segment was 38.75 Mb,
      extending from 2q33.1 to 2q37.3 and the size of the terminal deletion was 2.85 Mb
      in 2q37.3. Our results indicate that the inv dup del (2q) is likely a non
      recurrent chromosomal rearrangement generated by a NHEJ mechanism. The major
      clinical characteristics associated with this 2q rearrangement overlap with those
      commonly found in patients with 2q duplication reported in the literature.

PMID- 20799322
TI  - Communication of biobanks' research results: what do (potential) participants
      want?
AB  - The aim of this study was to investigate (potential) research participants' (a)
      information preferences with regard to receiving biobanks' genetic research
      results, and (b) attitudes towards the duties of researchers to communicate
      research results. A total group of 1,678 was analyzed, consisting of a sample of
      the general Dutch population (N=1,163) and patients with asthma, rhinitis, and
      thrombosis (N=515) who completed a survey including six fictitious genetic
      research results each presented as aggregate and individual result, varied for
      treatability and kind of disease. Five questions assessed attitudes towards
      researchers' duties to communicate research results. Additionally, background
      characteristics were measured. A majority of the respondents wanted to receive
      aggregate results as well as individual results. A small majority (59%) held the
      view that researchers should communicate individual results with no health
      consequences. One third agreed with an information duty only when treatment is
      available. A preference for individual results and an attitude in favor of
      communicating results were both associated with belonging to the general Dutch
      population rather than being a patient, wanting to learn about own health as the
      reason for biobank-participation, a monitoring coping style, a general desire for
      health information, perceived meaningfulness of genetic information and no
      anticipated anxiousness. A sizable majority of respondents showed a high
      information preference for individual results, even when it is unclear that
      treatment is available. Fewer were of the opinion that researchers should make
      this possible. For their communication policy biobanks should take notice of
      (potential) participants' high information preferences and expectations.

PMID- 20799324
TI  - A de novo p.Asp18Asn mutation in TREX1 in a patient with Aicardi-Goutieres
      syndrome.
AB  - Aicardi-Goutieres syndrome is a rare, genetically determined encephalopathy often
      resembling congenital infection. Mutations in the TREX1 gene are found in
      approximately 25% of patients. Aicardi-Goutieres syndrome is usually inherited as
      an autosomal recessive trait, although a single case of a heterozygous TREX1
      mutation associated with the syndrome has been reported. We present a second case
      of a de novo heterozygous TREX1 mutation causing an autosomal dominant phenotype
      of Aicardi-Goutieres syndrome with additional features indicative of
      mitochondrial dysfunction. This report serves to enhance awareness of de novo
      heterozygous mutations underlying Aicardi-Goutieres syndrome-with a concomitant
      low risk of recurrence.

PMID- 20799323
TI  - Characterization of the chromosome 1q41q42.12 region, and the candidate gene
      DISP1, in patients with CDH.
AB  - Cytogenetic and molecular cytogenetic studies demonstrate association between
      congenital diaphragmatic hernia (CDH) and chromosome 1q41q42 deletions. In this
      study, we screened a large CDH cohort (N=179) for microdeletions in this interval
      by the multiplex ligation-dependent probe amplification (MLPA) technique, and
      also sequenced two candidate genes located therein, dispatched 1 (DISP1) and homo
      sapiens H2.0-like homeobox (HLX). MLPA analysis verified deletions of this region
      in two cases, an unreported patient with a 46,XY,del(1)(q41q42.13) karyotype and
      a previously reported patient with a Fryns syndrome phenotype [Kantarci et al.,
      2006]. HLX sequencing showed a novel but maternally inherited single nucleotide
      variant (c.27C>G) in a patient with isolated CDH, while DISP1 sequencing revealed
      a mosaic de novo heterozygous substitution (c.4412C>G; p.Ala1471Gly) in a male
      with a left-sided Bochdalek hernia plus multiple other anomalies. Pyrosequencing
      demonstrated the mutant allele was present in 43%, 12%, and 4.5% of the patient's
      lymphoblastoid, peripheral blood lymphocytes, and saliva cells, respectively. We
      examined Disp1 expression at day E11.5 of mouse diaphragm formation and confirmed
      its presence in the pleuroperitoneal fold, as well as the nearby lung which also
      expresses Sonic hedgehog (Shh). Our report describes the first de novo DISP1
      point mutation in a patient with complex CDH. Combining this finding with Disp1
      embryonic mouse diaphragm and lung tissue expression, as well as previously
      reported human chromosome 1q41q42 aberrations in patients with CDH, suggests that
      DISP1 may warrant further consideration as a CDH candidate gene.

PMID- 20799325
TI  - Introductory comments on special section-new developments in craniofacial
      biology: putting on a happy face.
AB  - Approximately three quarters of children with birth defects have anomalies that
      affect the craniofacial structures. Defects in this area of the body result in
      lifelong disability, major challenges to families and society and often a serious
      effect on life expectancy. Surgery has been the primary intervention for these
      disorders, with frequently less than optimal outcomes and risk for additional
      morbidity and mortality. The challenge for clinicians caring for these children
      is to develop new methods for the treatment and prevention of these disorders. An
      understanding of the evolution of the head and the finely tuned temporospatial
      signaling pathways involved is critical to understanding the origins of the
      vertebrates as well as of human craniofacial malformations. In the future, these
      new approaches will be based upon our enhanced understanding of the developmental
      tool kit fashioned by evolution and the application of this knowledge toward the
      development of new diagnostic, pharmacologic, and genetic interventions for these
      disorders.

PMID- 20799326
TI  - Mutations in the G6PC3 gene cause Dursun syndrome.
AB  - Dursun syndrome is a triad of familial primary pulmonary hypertension,
      leucopenia, and atrial septal defect. Here we demonstrate that mutations in G6PC3
      cause Dursun syndrome. Mutations in G6PC3 are known to also cause severe
      congenital neutropenia type 4. Identification of the genetic basis of Dursun
      syndrome expands the pre-existing knowledge about the phenotypic effects of
      mutations in G6PC3. We propose that Dursun syndrome should now be considered as a
      subset of severe congenital neutropenia type 4 with pulmonary hypertension as an
      important clinical feature.

PMID- 20799327
TI  - Genetic Drift. The ancient Egyptian dwarfs of the Walters Art Museum.
AB  - The ancient Egyptians left an impressive artistic legacy documenting many aspects
      of their society including the existence of dwarfs as highly valued members. In
      previous publications in the Journal, I discussed dwarfs and skeletal dysplasia
      in ancient Egypt. In this study, I examined the ancient Egyptian representations
      of dwarfs of the Walters Art Museum in Baltimore, Maryland. One of the highlights
      of the collection is a group of five ivory figurines from Predynastic Times (pre
      3500-3100 BCE) depicting a couple, a man with a child, and two females.
      Representations from other periods include ordinary as well as dwarf deities. The
      dwarf gods, Bes and Ptah, are frequently depicted holding or biting snakes or
      standing on crocodiles symbolizing their ability to ward off dangers. A couple of
      statuettes from the Greco-Roman Period that, in contrast to earlier Egyptian
      Periods, depict harsh physical anomalies, twisted bodies, and facial pain. The
      artistic impression can be interpreted as either tragic or humorous. The
      grotesque depiction of dwarfs during the Greco-Roman Period in ancient Egypt is
      believed to be due to a greater infusion of Hellenistic influence. This study
      provides a microcosm of the legacy of dwarfs in ancient Egypt and supports the
      premise that dwarfs were accepted and integrated in the ancient Egyptian society,
      and with a few exceptions, their disorder was not depicted as a physical
      handicap.

PMID- 20799328
TI  - Comparative cranial osteology of fossorial lizards from the tribe Gymnophthalmini
      (Squamata, Gymnophthalmidae).
AB  - Squamates (lizards, snakes and amphisbaenians) are represented by a large number
      of species distributed among a wide variety of habitats. Changes in body plan
      related to a fossorial habit are a frequent trend within the group and many
      morphological adaptations to this particular lifestyle evolved convergently in
      nonrelated species, reflecting adaptations to a similar habitat. The fossorial
      lifestyle requires an optimal morphological organization for an effective use of
      the available resources. Skeleton arrangement in fossorial squamates reflects
      adaptations to the burrowing activity, and different degrees of fossoriality can
      be inferred through an analysis of skull morphology. Here, we provide a detailed
      description of the skull morphology of three fossorial gymnophthalmid species:
      Calyptommatus nicterus, Scriptosaura catimbau, and Nothobachia ablephara.

PMID- 20799329
TI  - Collagen XVIII mutation in Knobloch syndrome with acute lymphoblastic leukemia.
AB  - Knobloch syndrome (KNO) is caused by mutations in the collagen XVIII gene
      (COL18A1) and patients develop encephalocele and vitreoretinal degeneration.
      Here, we report an El Salvadorian family where two sisters showed features of
      KNO. One of the siblings also developed acute lymphoblastic leukemia. DNA
      sequencing of COL18A1 revealed a homozygous, 2-bp deletion (c3514-3515delCT) in
      exon 41, which leads to abnormal collagen XVIII and deficiency of its proteolytic
      cleavage product endostatin. KNO patients with mutations in COL18A1 may be at
      risk for endostatin-related conditions including malignancy.

PMID- 20799330
TI  - Barber-Say syndrome in a father and daughter.
AB  - We report on a father to daughter transmission of Barber-Say syndrome (BSS), a
      rare, congenital disorder characterized by severe generalized hypertrichosis,
      macrostomia, ocular telecanthus, bulbous nose and atrophic skin. These two cases
      further support the autosomal dominant inheritance. Both presented with the
      typical BSS symptoms but the phenotypic expression in the father was milder.
      Treatment is challenging for both patients and doctors, requiring a
      multidisciplinary approach.

PMID- 20799331
TI  - 11q14.1-11q22.1 deletion in a 1-year-old male with minor dysmorphic features.

PMID- 20799332
TI  - IRF6 polymorphisms are associated with nonsyndromic orofacial clefts in a Chinese
      Han population.
AB  - IRF6 plays an important role in orofacial development. In the present study, we
      genotyped two polymorphisms (rs642961 and rs2235371) within the IRF6 locus and
      estimated their associations with risk of nonsyndromic orofacial clefts (NSOC),
      including the subgroups, in a hospital-based case-control study in a Chinese Han
      population. In the single locus analyses, we found rs642961 AG and AG/AA
      genotypes were associated with increased risk of NSOC, especially cleft lip with
      or without cleft palate (CL/P) and cleft lip with cleft palate (CLP), while
      significantly decreased risks were associated with rs2235371 CT and CT/TT
      genotypes. When examining the combined effects of these two polymorphisms and
      using the rs642961 A and rs2235371 C alleles as the risk alleles, we found
      genotypes containing 2-4 risk alleles conferred high risk to NSOC, CL/P, and CLP.
      Furthermore, to test whether rs642961 could modulate IRF6 expression in vivo, we
      surgically collected lip skin tissues within the adjacent region of lip cleft
      site and found rs642961 genotypes were associated with differential levels of
      IRF6 mRNA and protein expression in an allele-dosage manner, providing the first
      evidence that rs642961 affected IRF6 expression in vivo. Taken together, these
      findings confirm the contribution of IRF6 genetic variants in the etiology of
      NSOC in a Chinese Han population.

PMID- 20799333
TI  - A Runx1 intronic enhancer marks hemogenic endothelial cells and hematopoietic
      stem cells.
AB  - Runx1 is essential for the generation of hematopoietic stem cells (HSCs) and is
      frequently mutated in human leukemias. However, the cis-regulatory mechanisms
      modulating the Runx1 gene expression remain to be elucidated. Herewith, we report
      the identification of an intronic Runx1 enhancer, Runx1 +24 mouse conserved
      noncoding element (mCNE), using a combinatorial in silico approach involving
      comparative genomics and retroviral integration sites mapping. The Runx1 +24 mCNE
      was found to possess hematopoietic-specific enhancer activity in both zebrafish
      and mouse models. Significantly, this enhancer is active specifically in
      hemogenic endothelial cells (ECs) at sites where the de novo generation of HSCs
      occurs. The activity of this enhancer is also strictly restricted to HSCs within
      the hematopoietic compartment of the adult bone marrow. We anticipate that Runx1
      +24 mCNE HSC enhancer will serve as a molecular handle for tracing and/or
      manipulating hemogenic ECs/HSCs behavior in vivo, and consequently become an
      invaluable tool for research on stem cell and cancer biology.

PMID- 20799334
TI  - ETV5 regulates sertoli cell chemokines involved in mouse stem/progenitor
      spermatogonia maintenance.
AB  - Spermatogonial stem cells are the only stem cells in the body that transmit
      genetic information to offspring. Although growth factors responsible for self
      renewal of these cells are known, the factors and mechanisms that attract and
      physically maintain these cells within their microenvironment are poorly
      understood. Mice with targeted disruption of Ets variant gene 5 (Etv5) show total
      loss of stem/progenitor spermatogonia following the first wave of
      spermatogenesis, resulting in a Sertoli cell-only phenotype and aspermia.
      Microarray analysis of primary Sertoli cells from Etv5 knockout (Etv5(-/-))
      versus wild-type (WT) mice revealed significant decreases in expression of
      several chemokines. Chemotaxis assays demonstrated that migration of
      stem/progenitor spermatogonia toward Etv5(-/-) Sertoli cells was significantly
      decreased compared to migration toward WT Sertoli cells. Interestingly,
      differentiating spermatogonia, spermatocytes, and round spermatids were not
      chemoattracted by WT Sertoli cells, whereas stem/progenitor spermatogonia showed
      a high and significant chemotactic index. Rescue assays using recombinant
      chemokines indicated that C-C-motif ligand 9 (CCL9) facilitates Sertoli cell
      chemoattraction of stem/progenitor spermatogonia, which express C-C-receptor type
      1 (CCR1). In addition, there is protein-DNA interaction between ETV5 and Ccl9,
      suggesting that ETV5 might be a direct regulator of Ccl9 expression. Taken
      together, our data show for the first time that Sertoli cells are chemoattractive
      for stem/progenitor spermatogonia, and that production of specific chemokines is
      regulated by ETV5. Therefore, changes in chemokine production and consequent
      decreases in chemoattraction by Etv5(-/-) Sertoli cells helps to explain
      stem/progenitor spermatogonia loss in Etv5(-/-) mice.

PMID- 20799335
TI  - Myoblast-derived neuronal cells form glutamatergic neurons in the mouse
      cerebellum.
AB  - Production of neurons from non-neural cells has far-reaching clinical
      significance. We previously found that myoblasts can be converted to a
      physiologically active neuronal phenotype by transferring a single recombinant
      transcription factor, REST-VP16, which directly activates target genes of the
      transcriptional repressor, REST. However, the neuronal subtype of M-RV cells and
      whether they can establish synaptic communication in the brain have remained
      unknown. M-RV cells engineered to express green fluorescent protein (M-RV-GFP)
      had functional ion channels but did not establish synaptic communication in
      vitro. However, when transplanted into newborn mice cerebella, a site of
      extensive postnatal neurogenesis, these cells expressed endogenous cerebellar
      granule precursors and neuron proteins, such as transient axonal glycoprotein-1,
      neurofilament, type-III beta-tubulin, superior cervical ganglia-clone 10,
      glutamate receptor-2, and glutamate decarboxylase. Importantly, they exhibited
      action potentials and were capable of receiving glutamatergic synaptic input,
      similar to the native cerebellar granule neurons. These results suggest that M-RV
      GFP cells differentiate into glutamatergic neurons, an important neuronal
      subtype, in the postnatal cerebellar milieu. Our findings suggest that although
      activation of REST-target genes can reprogram myoblasts to assume a general
      neuronal phenotype, the subtype specificity may then be directed by the brain
      microenvironment.

PMID- 20799336
TI  - Gli1 is an inducing factor in generating floor plate progenitor cells from human
      embryonic stem cells.
AB  - Generation of mesencephalic dopamine (mesDA) neurons from human embryonic stem
      cells (hESCs) requires several stages of signaling from various extrinsic and
      intrinsic factors. To date, most methods incorporate exogenous treatment of Sonic
      hedgehog (SHH) to derive mesDA neurons. However, we and others have shown that
      this approach is inefficient for generating FOXA2+ cells, the precursors of mesDA
      neurons. As mesDA neurons are derived from the ventral floor plate (FP) regions
      of the embryonic neural tube, we sought to develop a system to derive FP cells
      from hESC. We show that forced expression of the transcription factor GLI1 in
      hESC at the earliest stage of neural induction, resulted in their commitment to
      FP lineage. The GLI1+ cells coexpressed FP markers, FOXA2 and Corin, and
      displayed exocrine SHH activity by ventrally patterning the surrounding neural
      progenitors. This system results in 63% FOXA2+ cells at the neural progenitor
      stage of hESC differentiation. The GLI1-transduced cells were also able to
      differentiate to neurons expressing tyrosine hydroxylase. This study demonstrates
      that GLI1 is a determinant of FP specification in hESC and describes a highly
      robust and efficient in vitro model system that mimics the ventral neural tube
      organizer.

PMID- 20799338
TI  - Evidence for a recurrent microdeletion at chromosome 16p11.2 associated with
      congenital anomalies of the kidney and urinary tract (CAKUT) and Hirschsprung
      disease.
AB  - Congenital Anomalies of the Kidney and Urinary Tract can be associated with
      Hirschsprung disease. We report on three children with a similar 16p11.2
      microdeletion with a spectrum of clinical anomalies consisting of congenital
      anomalies of the kidney and urinary tract in two patients (Patients 1 and 2) and
      Hirschsprung disease in two patients (Patients 1 and 3), leading us to
      hypothesize that a gene in this region is associated with these phenotypes.
      Patient 1 presented with left renal agenesis, grade-IV vesicoureteral reflux, and
      Hirschsprung disease, Patient 2 with left renal agenesis, chronic kidney disease,
      chronic constipation, seizures, and developmental delay, and Patient 3 with
      Hirschsprung disease and normal kidneys. Genome-wide microarray analysis
      demonstrated overlapping microdeletions within 16p11.2. The shortest region of
      overlap in the three patients contained only eight genes, including the SH2
      domain-containing binding protein 1 (SH2B1), an adaptor protein which has been
      implicated in enhancement of the tyrosine kinase activity of RET, whose role in
      developmental disease of the kidney and enteric enervation is well established.
      Our findings suggest that 16p11.2 deletions are associated with abnormalities of
      renal and enteric development and we hypothesize that deletion of SH2B1 may
      account for the observed phenotype.

PMID- 20799337
TI  - Identification of novel FMR1 variants by massively parallel sequencing in
      developmentally delayed males.
AB  - Fragile X syndrome (FXS), the most common inherited form of developmental delay,
      is typically caused by CGG-repeat expansion in FMR1. However, little attention
      has been paid to sequence variants in FMR1. Through the use of pooled-template
      massively parallel sequencing, we identified 130 novel FMR1 sequence variants in
      a population of 963 developmentally delayed males without CGG-repeat expansion
      mutations. Among these, we identified a novel missense change, p.R138Q, which
      alters a conserved residue in the nuclear localization signal of FMRP. We have
      also identified three promoter mutations in this population, all of which
      significantly reduce in vitro levels of FMR1 transcription. Additionally, we
      identified 10 noncoding variants of possible functional significance in the
      introns and 3'-untranslated region of FMR1, including two predicted splice site
      mutations. These findings greatly expand the catalog of known FMR1 sequence
      variants and suggest that FMR1 sequence variants may represent an important cause
      of developmental delay.

PMID- 20799339
TI  - Cranial functional morphology of fossil dogs and adaptation for durophagy in
      Borophagus and Epicyon (Carnivora, Mammalia).
AB  - Morphological specialization is a complex interplay of adaptation and constraint,
      as similarly specialized features often evolve convergently in unrelated species,
      indicating that there are universally adaptive aspects to these morphologies. The
      evolutionary history of carnivores offers outstanding examples of convergent
      specialization. Among larger predators, borophagine canids were highly abundant
      during the tertiary of North America and are regarded as the ecological vicars of
      Afro-Eurasian hyenas. Borophaginae is an extinct group of 60+ species, the
      largest forms evolving robust skulls with prominently domed foreheads, short
      snouts, and hypertrophied fourth premolars. These specializations have been
      speculated to enhance bone cracking. To test the extent that the skulls of
      derived borophagines were adapted for producing large bite forces and
      withstanding the mechanical stresses associated with bone cracking relative to
      their nonrobust sister clades, we manipulated muscle forces in models of six
      canid skulls and analyzed their mechanical response using 3D finite element
      analysis. Performance measures of bite force production efficiency and
      deformation minimization showed that skulls of derived borophagines Borophagus
      secundus and Epicyon haydeni are particularly strong in the frontal region;
      maximum stresses are lower and more evenly distributed over the skull than in
      other canids. Frontal strength is potentially coupled with a temporalis-driven
      bite to minimize cranial stress during biting in the two derived genera, as
      tensile stress incurred by contracting temporalis muscles is dissipated rostro
      ventrally across the forehead and face. Comparison of estimated masticatory
      muscle cross section areas suggests that the temporalis-masseter ratio is not
      strongly associated with morphological adaptations for bone cracking in
      Borophagus and Epicyon; larger body size may explain relatively larger temporalis
      muscles in the latter. When compared with previous studies, the overall cranial
      mechanics of the derived borophagines is more similar to bone-cracking hyaenids
      and percrocutids than to their canid relatives, indicating convergence in both
      morphological form and functional capability.

PMID- 20799340
TI  - Diffusion tensor-based regional gray matter tissue segmentation using the
      international consortium for brain mapping atlases.
AB  - In this communication, we extended a previously described and validated diffusion
      tensor imaging (DTI) method for segmenting whole brain cerebrospinal fluid (CSF)
      and gray and white matter (WM) tissue to provide regional volume and DTI metrics
      of WM tract and cortical and subcortical gray matter. This DTI-based regional
      segmentation was implemented using the statistical parametric mapping (SPM)
      toolbox and used the international consortium for brain mapping atlases and
      Montreal Neurological Institute brain templates. We used our DTI-based
      segmentation approach to calculate the left putamen volume in a cohort of 136
      healthy right-handed males and females aged 15.8-62.8 years. We validated our
      approach by demonstrating its sensitivity to age-related changes of the putamen.
      Indeed, our method found that the putamen volume decreased with age (r = -0.30; P
      < 0.001) while the corresponding fractional anisotropy (FA) increased with
      advancing age (r = 0.5; P < 0.00001). It is then demonstrated, on a subset of our
      cohort (n = 31), that the putamen volume obtained by our method correlated with
      measurements obtained from FreeSurfer (r = 0.396, P < 0.05). Our novel approach
      increases the information obtained with a DTI examination by providing routine
      volumetry measure, thereby eliminating separate scans to obtain volumetry data.
      In addition, the labeled volumes obtained with our method have the potential to
      increase the accuracy of fiber tracking. In the future, this new approach can be
      automated to analyze large data sets to help discover noninvasive neuroimaging
      markers for clinical trials and brain-function studies in both health and
      disease.

PMID- 20799341
TI  - Overlapping high-resolution copy number alterations in cancer genomes identified
      putative cancer genes in hepatocellular carcinoma.
AB  - Recurrent cancer genome aberrations are indicators of residing crucial cancer
      genes. Although recent advances in genomic technologies have led to a global view
      of cancer genome aberrations, the identification of target genes and biomarkers
      from the aberrant loci remains difficult. To facilitate searches of cancer genes
      in human hepatocellular carcinoma (HCC), we established a comprehensive protocol
      to analyze copy number alterations (CNAs) in cancer genomes using high-density
      single nucleotide polymorphism arrays with unpaired reference genomes. We
      identified common HCC genes by overlapping the shared aberrant loci in multiple
      cell lines with functional validation and clinical implications. A total of 653
      amplicons and 57 homozygous deletions (HDs) were revealed in 23 cell lines. To
      search for novel HCC genes, we overlapped aberrant loci to uncover 6 HDs and 126
      amplicons shared by at least two cell lines. We selected two novel genes,
      fibronectin type III domain containing 3B (FNDC3B) at the 3q26.3 overlapped
      amplicon and solute carrier family 29 member 2 (SLC29A2) at the 11q13.2
      overlapped amplicon, to investigate their aberrations in HCC tumorigenesis.
      Aberrant up-regulation of FNDC3B and SLC29A2 occurred in multiple HCC data sets.
      Knockdown of these genes in amplified cells decreased cell proliferation,
      anchorage-independent growth, and tumor formation in xenograft models.
      Importantly, up-regulation of SLC29A2 in HCC tissues was significantly associated
      with advanced stages (P = 0.0031), vascular invasion (P = 0.0353), and poor
      patient survival (P = 0.0325). Overexpression of FNDC3B or SLC29A2 in unamplified
      HCC cells promoted cell proliferation through activation of the signal transducer
      and activator of transcription 3 signaling pathway. CONCLUSION: A standardized
      genome-wide CNA analysis protocol using data from user-generated or public
      domains normalized with unpaired reference genomes has been established to
      facilitate high-throughput detection of cancer genes as significant target genes
      and biomarkers for cancer diagnosis and therapy.

PMID- 20799342
TI  - Estimation of life-years gained and cost effectiveness based on cause-specific
      mortality.
AB  - Cost-effectiveness analysis is usually based on life-years gained estimated from
      all-cause mortality. When an intervention affects only a few causes of death
      accounting for a small fraction of all deaths, this approach may lack precision.
      We develop a novel technique for cost-effectiveness analysis when life-years
      gained are estimated from cause-specific mortality, allowing for competing causes
      of death. In the context of randomised trial data, we adjust for other-cause
      mortality combined across randomised groups. This method yields a greater
      precision than analysis based on total mortality, and we show application to life
      years gained, quality-adjusted life-years gained, incremental costs, and cost
      effectiveness. In multi-state health economic models, however, mortality from
      competing causes is commonly derived from national statistics and is assumed to
      be known and equal across intervention groups. In such models, our method based
      on cause-specific mortality and standard methods using total mortality give
      essentially identical estimates and precision. The methods are applied to a
      randomised trial and a health economic model, both of screening for abdominal
      aortic aneurysm. A gain in precision for cost-effectiveness estimates is clearly
      helpful for decision making, but it is important to ensure that 'cause-specific
      mortality' is defined to include all causes of death potentially affected by the
      intervention.

PMID- 20799343
TI  - Using discrete choice experiments to value informal care tasks: exploring
      preference heterogeneity.
AB  - While informal care is a significant part of non-market economic activity, its
      value is rarely acknowledged, perhaps reflecting a lack of market data.
      Traditional methods to value such care include opportunity and replacement cost.
      This study is the first to employ the discrete choice experiment methodology to
      value informal care tasks. A monetary value is estimated for three tasks
      (personal care, supervising and household tasks). The relationship between time
      spent on formal and informal care is also modelled and preference heterogeneity
      investigated using the Latent Class Model. Complementarity between supervising
      tasks and formal care is observed. Monetary compensation is important, with
      willingness to accept per hour values ranging from L0.38 to L0.83 for personal
      care, L0.75 for supervising and L0.31 to L0.6 for household tasks. Heterogeneity
      in preferences is observed, with monetary compensation being important for
      younger people, but insignificant for older individuals. Such heterogeneity is
      important at the policy level. Values are lower than those generated by
      opportunity cost and replacement cost methods, perhaps because of the limited
      ability of revealed preference methods to capture broader aspect of utility.
      Differences with contingent valuation methods are also observed, suggesting
      future research should investigate the external validity of the different
      methods.

PMID- 20799345
TI  - Mixtures of Uncaria and Tabebuia extracts are potentially chemopreventive in
      CBA/Ca mice: a long-term experiment.
AB  - A long-term experimental animal model was developed by our research group for the
      evaluation of potential chemopreventive effects. The inhibitory effects of agents
      on carcinogen (7,12-dimethylbenz[a]anthracene (DMBA) induced molecular
      epidemiological biomarkers, in this case the expression of key onco/suppressor
      genes were investigated. The expression pattern of c-myc, Ha-ras, Bcl-2, K-ras
      protooncogene and p53 tumour suppressor gene were studied to elucidate early
      carcinogenic and potential chemopreventive effects. The consumption of so-called
      Claw of Dragon tea (CoDTM tea) containing the bark of Uncaria guianensis, Cat's
      Claw (Uncaria sp. U. tomentosa) and Palmer trumpet-tree (Tabebuia sp. T.
      avellanedae) was able to decrease the DMBA-induced onco/suppressor gene
      overexpression in a short-term animal experiment. In a following study CBA/Ca
      mice were treated with 20 mg/kg bw DMBA intraperitoneally (i.p.) and the
      expression patterns of onco/suppressor genes were examined at several time
      intervals. According to the examined gene expression patterns in this long-term
      experiment the chemopreventive effect of CoDTM tea consumption could be
      confirmed.

PMID- 20799344
TI  - Review of statistical methods for analysing healthcare resources and costs.
AB  - We review statistical methods for analysing healthcare resource use and costs,
      their ability to address skewness, excess zeros, multimodality and heavy right
      tails, and their ease for general use. We aim to provide guidance on analysing
      resource use and costs focusing on randomised trials, although methods often have
      wider applicability. Twelve broad categories of methods were identified: (I)
      methods based on the normal distribution, (II) methods following transformation
      of data, (III) single-distribution generalized linear models (GLMs), (IV)
      parametric models based on skewed distributions outside the GLM family, (V)
      models based on mixtures of parametric distributions, (VI) two (or multi)-part
      and Tobit models, (VII) survival methods, (VIII) non-parametric methods, (IX)
      methods based on truncation or trimming of data, (X) data components models, (XI)
      methods based on averaging across models, and (XII) Markov chain methods. Based
      on this review, our recommendations are that, first, simple methods are preferred
      in large samples where the near-normality of sample means is assured. Second, in
      somewhat smaller samples, relatively simple methods, able to deal with one or two
      of above data characteristics, may be preferable but checking sensitivity to
      assumptions is necessary. Finally, some more complex methods hold promise, but
      are relatively untried; their implementation requires substantial expertise and
      they are not currently recommended for wider applied work.

PMID- 20799346
TI  - Analysis of changes in tyrosine and serine phosphorylation of red cell membrane
      proteins induced by P. falciparum growth.
AB  - Phosphorylation of erythrocyte membrane proteins has been previously documented
      following infection and intracellular growth of the malarial parasite, Plasmodium
      falciparum in red cells. Much of this data dealt with phosphorylation of serine
      residues. In this study, we report detailed characterization of phosphorylation
      of serine and tyrosine residues of red cell membrane proteins following infection
      by P falciparum. Western blot analysis using anti-phosphotyrosine and anti
      phosphoserine antibodies following 2-DE in conjunction with double channel laser
      induced infrared fluorescence enabled accurate assessment of phosphorylation
      changes. Tyrosine phosphorylation of band 3 represented the earliest modification
      observed during parasite development. Band 3 tyrosine phosphorylation observed at
      the ring stage appears to be under the control of Syk kinase. Serine and tyrosine
      phosphorylation of additional cytoskeletal, trans-membrane and membrane
      associated proteins was documented as intracellular development of parasite
      progressed. Importantly, during late schizont stage of parasite maturation, we
      observed widespread protein dephosphorylation. In vitro treatments that caused
      distinct activation of red cell tyrosine and serine kinases elicited
      phosphorylative patterns similar to what observed in parasitized red blood cell,
      suggesting primary involvement of erythrocyte kinases. Identification of tyrosine
      phosphorylations of band 3, band 4.2, catalase and actin which have not been
      previously described in P. falciparum infected red cells suggests new potential
      regulatory mechanisms that could modify the functions of the host cell membrane.

PMID- 20799347
TI  - Experimental optimization of protein refolding with a genetic algorithm.
AB  - Refolding of proteins from solubilized inclusion bodies still represents a major
      challenge for many recombinantly expressed proteins and often constitutes a major
      bottleneck. As in vitro refolding is a complex reaction with a variety of
      critical parameters, suitable refolding conditions are typically derived
      empirically in extensive screening experiments. Here, we introduce a new strategy
      that combines screening and optimization of refolding yields with a genetic
      algorithm (GA). The experimental setup was designed to achieve a robust and
      universal method that should allow optimizing the folding of a variety of
      proteins with the same routine procedure guided by the GA. In the screen, we
      incorporated a large number of common refolding additives and conditions. Using
      this design, the refolding of four structurally and functionally different model
      proteins was optimized experimentally, achieving 74-100% refolding yield for all
      of them. Interestingly, our results show that this new strategy provides optimum
      conditions not only for refolding but also for the activity of the native enzyme.
      It is designed to be generally applicable and seems to be eligible for all
      enzymes.

PMID- 20799348
TI  - The crystal structure Escherichia coli Spy.
AB  - Escherichia coli spheroplast protein y (EcSpy) is a small periplasmic protein
      that is homologous with CpxP, an inhibitor of the extracytoplasmic stress
      response. Stress conditions such as spheroplast formation induce the expression
      of Spy via the Cpx or the Bae two-component systems in E. coli, though the
      function of Spy is unknown. Here, we report the crystal structure of EcSpy, which
      reveals a long kinked hairpin-like structure of four alpha-helices that form an
      antiparallel dimer. The dimer contains a curved oval shape with a highly
      positively charged concave surface that may function as a ligand binding site.
      Sequence analysis reveals that Spy is highly conserved over the
      Enterobacteriaceae family. Notably, three conserved regions that contain
      identical residues and two LTxxQ motifs are placed at the horizontal end of the
      dimer structure, stabilizing the overall fold. CpxP also contains the conserved
      sequence motifs and has a predicted secondary structure similar to Spy,
      suggesting that Spy and CpxP likely share the same fold.

PMID- 20799349
TI  - A lead discovery strategy driven by a comprehensive analysis of proteases in the
      peptide substrate space.
AB  - We present here a comprehensive analysis of proteases in the peptide substrate
      space and demonstrate its applicability for lead discovery. Aligned octapeptide
      substrates of 498 proteases taken from the MEROPS peptidase database were used
      for the in silico analysis. A multiple-category naive Bayes model, trained on the
      two-dimensional chemical features of the substrates, was able to classify the
      substrates of 365 (73%) proteases and elucidate statistically significant
      chemical features for each of their specific substrate positions. The positional
      awareness of the method allows us to identify the most similar substrate
      positions between proteases. Our analysis reveals that proteases from different
      families, based on the traditional classification (aspartic, cysteine, serine,
      and metallo), could have substrates that differ at the cleavage site (P1-P1') but
      are similar away from it. Caspase-3 (cysteine protease) and granzyme B (serine
      protease) are previously known examples of cross-family neighbors identified by
      this method. To assess whether peptide substrate similarity between unrelated
      proteases could reliably translate into the discovery of low molecular weight
      synthetic inhibitors, a lead discovery strategy was tested on two other cross
      family neighbors--namely cathepsin L2 and matrix metallo proteinase 9, and
      calpain 1 and pepsin A. For both these pairs, a naive Bayes classifier model
      trained on inhibitors of one protease could successfully enrich those of its
      neighbor from a different family and vice versa, indicating that this approach
      could be prospectively applied to lead discovery for a novel protease target with
      no known synthetic inhibitors.

PMID- 20799350
TI  - Functional hot spots in human ATP-binding cassette transporter nucleotide binding
      domains.
AB  - The human ATP-binding cassette (ABC) transporter superfamily consists of 48
      integral membrane proteins that couple the action of ATP binding and hydrolysis
      to the transport of diverse substrates across cellular membranes. Defects in 18
      transporters have been implicated in human disease. In hundreds of cases, disease
      phenotypes and defects in function can be traced to nonsynonymous single
      nucleotide polymorphisms (nsSNPs). The functional impact of the majority of ABC
      transporter nsSNPs has yet to be experimentally characterized. Here, we combine
      experimental mutational studies with sequence and structural analysis to describe
      the impact of nsSNPs in human ABC transporters. First, the disease associations
      of 39 nsSNPs in 10 transporters were rationalized by identifying two conserved
      loops and a small alpha-helical region that may be involved in interdomain
      communication necessary for transport of substrates. Second, an approach to
      discriminate between disease-associated and neutral nsSNPs was developed and
      tailored to this superfamily. Finally, the functional impact of 40 unannotated
      nsSNPs in seven ABC transporters identified in 247 ethnically diverse individuals
      studied by the Pharmacogenetics of Membrane Transporters consortium was
      predicted. Three predictions were experimentally tested using human embryonic
      kidney epithelial (HEK) 293 cells stably transfected with the reference multidrug
      resistance transporter 4 and its variants to examine functional differences in
      transport of the antiviral drug, tenofovir. The experimental results confirmed
      two predictions. Our analysis provides a structural and evolutionary framework
      for rationalizing and predicting the functional effects of nsSNPs in this
      clinically important membrane transporter superfamily.

PMID- 20799351
TI  - Liver-specific suppressor of cytokine signaling-3 deletion in mice enhances
      hepatic insulin sensitivity and lipogenesis resulting in fatty liver and obesity.
AB  - Obesity is associated with chronic inflammation and contributes to the
      development of insulin resistance and nonalcoholic fatty liver disease. The
      suppressor of cytokine signaling-3 (SOCS3) protein is increased in inflammation
      and is thought to contribute to the pathogenesis of insulin resistance by
      inhibiting insulin and leptin signaling. Therefore, we studied the metabolic
      effects of liver-specific SOCS3 deletion in vivo. We fed wild-type (WT) and liver
      specific SOCS3 knockout (SOCS3 LKO) mice either a control diet or a high-fat diet
      (HFD) for 6 weeks and examined their metabolic phenotype. We isolated hepatocytes
      from WT and SOCS3 LKO mice and examined the effects of tumor necrosis factor
      alpha and insulin on Akt phosphorylation and fatty acid metabolism and lipogenic
      gene expression. Hepatocytes from control-fed SOCS3 LKO mice were protected from
      developing tumor necrosis factor alpha-induced insulin resistance but also had
      increased lipogenesis and expression of sterol response element-binding protein
      1c target genes. Lean SOCS3 LKO mice fed a control diet had enhanced hepatic
      insulin sensitivity; however, when fed an HFD, SOCS3 LKO mice had increased liver
      fat, inflammation, and whole-body insulin resistance. SOCS3 LKO mice fed an HFD
      also had elevated hypothalamic SOCS3 and fatty acid synthase expression and
      developed greater obesity due to increased food intake and reduced energy
      expenditure. CONCLUSION: Deletion of SOCS3 in the liver increases liver insulin
      sensitivity in mice fed a control diet but paradoxically promotes lipogenesis,
      leading to the development of nonalcoholic fatty liver disease, inflammation, and
      obesity.

PMID- 20799352
TI  - Noninvasive diagnostic criteria for hepatocellular carcinoma: a boat that leaks
      like a sieve.

PMID- 20799353
TI  - Alcohol septal ablation after myomectomy failure solutions for unusual cases.
AB  - We report an eight-year-old child presented with classical features of
      hypertrophic obstructive cardiomyopathy and with New York Heart Association
      (NYHA) class III symptoms, eight months after myectomy and refractory to medical
      treatment. Cardiac transplantation was indicated due to the severity of symptoms.
      But the lymphocyte reaction test showed almost 100% reaction of antibodies, and
      the surgeons rejected the heart transplantation for fear of hyperacute rejection.
      Then an alcohol septal ablation (ASA) was proposed, which was successfully
      performed on August 17, 2005. The post-extrasystolic gradient was reduced from
      160 to 60 mm Hg immediately and no other complications were seen. The child is
      being followed since then and echocardiography changes include a further
      reduction of septum thickness and gradient (P = 0.001), and important symptoms
      relieved after 3.5 years of follow up. ASA may be an option to be considered in
      children with critical hypertrophic obstructive cardiomyopathy in NYHA functional
      class III/IV, when other methods of treatment failed. (c) 2010 Wiley-Liss, Inc.

PMID- 20799354
TI  - The Bcl-xL inhibitor, ABT-737, efficiently induces apoptosis and suppresses
      growth of hepatoma cells in combination with sorafenib.
AB  - Tumor cells are characterized by uncontrolled proliferation, often driven by
      activation of oncogenes, and apoptosis resistance. The oncogenic kinase inhibitor
      sorafenib can significantly prolong median survival of patients with advanced
      hepatocellular carcinoma (HCC), although the response is disease-stabilizing and
      cytostatic rather than one of tumor regression. Bcl-xL (B cell lymphoma extra
      large), an antiapoptotic member of the B cell lymphoma-2 (Bcl-2) family, is
      frequently overexpressed in HCC. Here, we present in vivo evidence that Bcl-xL
      overexpression is directly linked to the rapid growth of solid tumors. We also
      examined whether ABT-737, a small molecule that specifically inhibits Bcl-xL but
      not myeloid cell leukemia-1 (Mcl-1), could control HCC progression, especially
      when used with sorafenib. Administration of ABT-737, even at an in vivo effective
      dose, failed to suppress Huh7 xenograft tumors in mice. ABT-737 caused the levels
      of Mcl-1 expression to rapidly increase by protein stabilization. This appeared
      to be related to resistance to ABT-737, because decreasing Mcl-1 expression
      levels to the baseline by a small interfering RNA-mediated strategy made hepatoma
      cells sensitive to this agent. Importantly, administration of ABT-737 to Mcl-1
      knockout mice induced severe liver apoptosis, suggesting that tumor-specific
      inhibition of Mcl-1 is required for therapeutic purposes. Sorafenib
      transcriptionally down-regulated Mcl-1 expression specifically in tumor cells and
      abolished Mcl-1 up-regulation induced by ABT-737. Sorafenib, not alone but in
      combination with ABT-737, efficiently induced apoptosis in hepatoma cells. This
      combination also led to stronger suppression of xenograft tumors than sorafenib
      alone. CONCLUSION: Bcl-xL inactivation by ABT-737 in combination with sorafenib
      was found to be safe and effective for anti-HCC therapy in preclinical models.
      Direct activation of the apoptosis machinery seems to unlock the antitumor
      potential of oncogenic kinase inhibitors and may produce durable clinical
      responses against HCC.

PMID- 20799355
TI  - Visceral adiposity index is associated with histological findings and high viral
      load in patients with chronic hepatitis C due to genotype 1.
AB  - Metabolic factors have been associated with liver damage in patients with
      genotype 1 chronic hepatitis C (G1 CHC). We tested visceral adiposity index
      (VAI), a new marker of adipose dysfunction in G1 CHC, patients to assess its
      association with host and viral factors and its link to both histological
      findings and sustained virological response (SVR). Two hundred thirty-six
      consecutive G1 CHC patients were evaluated by way of liver biopsy and
      anthropometric and metabolic measurements, including insulin resistance (IR),
      homeostasis model assessment (HOMA), and VAI using waist circumference, body mass
      index, triglycerides, and high-density lipoprotein cholesterol. All biopsies were
      scored by one pathologist for staging and grading and graded for steatosis, which
      was considered moderate to severe if >= 30%. Multiple linear regression analysis
      revealed that VAI score was independently associated with higher HOMA score (P =
      0.009), log10 hepatitis C virus RNA levels (P = 0.01), necroinflammatory activity
      (P = 0.04), and steatosis (P = 0.04). Multiple logistic regression analysis
      revealed that IR (OR 3.879, 95% CI 1.727-8.713, P = 0.001), higher VAI score (OR
      1.472, 95% CI 1.051-2.062, P = 0.02), and fibrosis (OR 2.255, 95% CI 1.349-3.768,
      P = 0.002) were linked to steatosis >= 30%. Logistic regression analysis revealed
      that older age (OR 1.030, 95% CI 1.002-1.059, P = 0.03), higher VAI score (OR
      1.618, 95% CI 1.001-2.617, P = 0.04), and fibrosis (OR 2.608, 95% CI 1.565-4.345,
      P < 0.001) were independently associated with moderate to severe
      necroinflammatory activity. No independent associations were found between VAI
      score and both fibrosis and SVR. CONCLUSION: In G1 CHC patients, higher VAI score
      is independently associated with both steatosis and necroinflammatory activity
      and has a direct correlation with viral load.

PMID- 20799356
TI  - Editorial: Canadian mass spectrometry: applications in medical research.

PMID- 20799357
TI  - Successful treatment of severe extremity pain in myelofibrosis with low-dose
      single-fraction radiation therapy.
AB  - Myelofibrosis (MF) is characterized by cytopenias/cytoses, leukoerythroblastic
      blood picture, bone marrow fibrosis, and extramedullary hematopoiesis. Extremity
      bone pain can be a feature of MF. There has been one case report of a patient
      with MF and bone pain treated with radiation. We treated five patients with MF
      and extremity pain with radiation at our institution between 2004 and 2010. All
      patients had severe pain unresponsive to narcotic medication. Radiation was one
      fraction of 100 to 600 cGy. Most patients saw improvement in the pain within days
      and achieved a complete response within days to weeks.The response lasted between
      1 month and 2 years. Retreatment was performed in four patients and achieved a
      durable response in three patients. No patients reported any acute or late side
      effects from radiation.Bone involvement in MF can cause disabling pain, but
      single-fraction low-dose radiation is a safe and effective treatment, often
      leading to a durable response. Retreatment is also safe and effective inpatients
      who experience recurrent pain.

PMID- 20799358
TI  - Different disparities of gender and race among the thrombotic thrombocytopenic
      purpura and hemolytic-uremic syndromes.
AB  - Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS)
      represent multiple disorders with diverse etiologies. We compared the gender and
      race of 335 patients enrolled in the Oklahoma TTP-HUS Registry across 21 years
      for their first episode of TTP or HUS to appropriate control groups. The relative
      frequency of women and white race among patients with TTP-HUS-associated with a
      bloody diarrhea prodrome and the relative frequency of women with quinine
      associated TTP-HUS were significantly greater than their control populations. The
      relative frequency of women and black race among patients with idiopathic TTP and
      TTP-associated with severe ADAMTS13 deficiency was significantly greater than
      their control populations. The relative frequency of black race among patients
      who had systemic lupus erythematosus (SLE) preceding TTP was significantly
      greater than among a population of patients with SLE, and the relative frequency
      of black race among patients with other autoimmune disorders preceding TTP was
      significantly greater than their control population. No significant gender or
      race disparities were present among patients with hematopoietic stem cell
      transplantation-associated thrombotic microangiopathy, TTP associated with
      pregnancy, or TTP associated with drugs other than quinine. The validity of these
      observations is supported by the enrollment of all consecutive patients across 21
      years from a defined geographic region, without selection or referral bias. These
      observations of different gender and race disparities among the TTP-HUS syndromes
      suggest the presence of different risk factors and may serve as starting points
      for novel investigations of pathogenesis.

PMID- 20799359
TI  - Beneficial effects of nitric oxide breathing in adult patients with sickle cell
      crisis.
AB  - Pain from vaso-occlusive crisis (VOC) is the major cause of hospitalization in
      patients with sickle cell disease (SCD). The beneficial therapeutic effects of
      inhaled nitric oxide (NO) on the pathophysiology of SCD have been reported. A
      double-blind, randomized, placebo-controlled clinical trial was conducted to
      determine whether NO breathing reduces acute VOC pain in adult patients and to
      study the safety of inhaled NO. Twenty-three patients experiencing acute VOC were
      enrolled. After randomization but before treatment, five were found to not meet
      final eligibility criteria. Nine patients were assigned to inhaled NO (80 ppm)
      and nine to placebo (21% O2). Primary outcome was the mean change in pain scores
      after 4 hr of inhalation, measured on a 10-cm visual analog scale (VAS). Both
      groups had similar baseline VAS pain scores but inhaled NO significantly reduced
      pain scores compared with placebo (P 5 0.02) at the end of NO inhalation.
      Secondary outcome was parenteral morphine use at baseline, 4, and 6 hr.
      Parenteral morphine use was lower in the inhaled NO group, but the difference was
      not statistically significant.Safety assessments included systolic blood pressure
      measurements,pulse oximetry readings, concentration of delivered nitrogen
      dioxide, and concentration of methemoglobin (metHb). None of these NO toxicities
      was observed.

PMID- 20799360
TI  - Follow-up report on the 2-year cardiac data from a deferasirox monotherapy trial.
AB  - The trial CICL670AUS04 was a single-arm, open-label study of the cardiac efficacy
      of 18 months of deferasirox monotherapy [1]. Cardiac response in this study was
      related to the degree of liver siderosis. Patients with mild to moderate liver
      siderosis improved their cardiac T2* while more severely siderotic patients did
      not, regardless of initial cardiac iron burden. In this letter, we report 2-year
      data in those patients who completed a 6-month extension phase (N 5 10). Cardiac
      and liver iron improved steadily during the 24-month period, with final cardiac
      T2* and LIC improving 37% and 27%, respectively, in this cohort. Serum ferritin
      and LVEF were not statistically different at anytime-point. When the extension
      phase (18-24 months) was considered in isolation, serum ferritin, liver iron
      concentration, and left ventricular ejection fraction were nearly identical to 18
      month results. Despite this, cardiac T2* continued to trend higher, increasing
      12.7% from 9.5 ms to 10.7 ms (P 5 0.06). Thus defersirox continued to demonstrate
      cardiac efficacy in patients with mild to moderate hepatic siderosis throughout 2
      years of therapy.

PMID- 20799361
TI  - Hemolytic anemia and distal renal tubular acidosis in two Indian patients
      homozygous for SLC4A1/AE1 mutation A858D.
AB  - Familial distal renal tubular acidosis (dRTA) can be caused by mutations in the
      Cl2/HCO32 exchanger of the renal Type A intercalated cell, kidney AE1/SLC4A1.
      dRTA-associated AE1 mutations have been reported in families from North America,
      Europe, Thailand, Malaysia, Papua-New Guinea, Taiwan, and the Philippines, but
      not India. The dRTA mutation AE1 A858D has been detected only in the context of
      compound heterozygosity. We report here two unrelated Indian patients with
      combined hemolytic anemia and dRTA who share homozygous A858D mutations of the
      AE1/SLC4A1 gene. The mutation creates a novel restriction site that is validated
      for diagnostic screening.

PMID- 20799362
TI  - Alteration in the pharmacokinetics of hemoglobin-vesicles in a rat model of
      chronic liver cirrhosis is associated with Kupffer cell phagocyte activity.
AB  - The hemoglobin-vesicle (HbV) is a cellular, hemoglobin-based oxygen carrier. Our
      previous pharmacokinetic studies demonstrated that the liver is strongly
      associated with the metabolism and excretion of HbV. The aim of this study was to
      evaluate the pharmacokinetics of HbV in a chronic cirrhosis rat (CCR) model
      induced by carbon tetrachloride (CCl(4) ) and explore whether liver functional
      parameters and Kupffer cell (KC) phagocyte activity are related to the
      pharmacokinetics of HbV. The CCRs were induced three times weekly by
      intraperitoneal administration of CCl(4) for 8 weeks and categorized as Child
      Pugh grade B. To analyze the pharmacokinetics, the CCRs were given a single
      intravenous injection of (3) H-HbV (1400 mg of Hb/kg). The total clearance and
      hepatic distribution of HbV were negatively correlated with plasma aspartate
      aminotransferase (AST) levels (p = 0.007). In addition, the phagocyte index was
      negatively correlated with plasma AST levels (p = 0.047). The excretion of lipid
      components in feces was also negatively correlated with plasma AST levels (p =
      0.049). In conclusion, alteration in the pharmacokinetics of HbV in CCRs can be
      attributed to a decrease in KC phagocyte activity and the extent of damage to
      parenchymal cells. This represents the first demonstration of the
      pharmacokinetics of a liposome preparation in chronic liverimpairment.

PMID- 20799363
TI  - Influence of Pluronic(r) F68 on ceftazidime biological activity in parenteral
      solutions.
AB  - beta-Lactam antimicrobials are known to have a low concentration/therapeutic
      response. However, extending the period in which beta-lactam are free in the
      plasma does directly influence therapeutic outcomes. The objective of this study
      was to evaluate the influence of Pluronic(r) F68 on the antimicrobial activity of
      ceftazidime when admixed with aminophylline in parenteral solutions by the
      evaluation of its minimal inhibitory concentration (MIC) within 24 h.
      Ceftazidime, aminophylline, and Pluronics(r) F68 were evaluated using the MIC
      method against Escherichia coli and Pseudomonas aeruginosa, with these compounds
      individually and associated in the same parenteral solutions. When Pluronics(r)
      F68 was admixtured with ceftazidime alone or with ceftazidime and aminophylline,
      it was possible to observe lower MIC values not only at 24 h but also at 0 h for
      both microorganisms. This indicates that Pluronics(r) F68 may be able to enhance
      ceftazidime antimicrobial activity in the presence or absence of aminophylline.
      This fact suggests that Pluronics(r) F68 can be applied to allow the
      administration of ceftazidime under continuous infusion in parenteral solutions,
      beneficiating hospital pharmacotherapy. It may also be possible to reduce
      ceftazidime doses in formulations achieving the same therapeutic results.

PMID- 20799364
TI  - Production of pH-responsive microparticles by spray drying: investigation of
      experimental parameter effects on morphological and release properties.
AB  - During spray drying, emphasis is placed on process optimisation to generate
      favourable particle morphological and flow properties. The effect of the initial
      feed solution composition on the drug release from the prepared microparticles
      (MPs) is rarely considered. We investigated the effects of solvent composition,
      feed solution concentration and drug-loading on sodium salicylate, hydrocortisone
      and triamcinolone release from spray-dried Eudragit L100 MPs. Eudragit L100 is a
      pH-responsive polymer whose dissolution threshold is pH 6 so dissolution testing
      of the prepared MPs at pH 5 and 1.2 illustrated non-polymer controlled burst
      release. Increasing the water content of the initial ethanolic feed solution
      significantly reduced hydrocortisone burst release at pH 5, as did reducing the
      feed solution concentration. These findings caution that changes in feed solution
      concentration or solvent composition not only affect particles' morphological
      characteristics but can also negatively alter their drug release properties. This
      work also illustrate that drug-free MPs can have different morphological
      properties to drug-loaded MPs. Therefore, process optimisation needs to be
      carried out using drug-loaded systems. Depending on the physicochemical
      properties of the encapsulated active pharmaceutical ingredient (API), drug
      loading can affect the polymer solubility in the initial feed solution with
      consequent impact on MPs morphological and release properties.

PMID- 20799365
TI  - A reliable predictive factorial model for entrapment optimization of a sodium
      bisphosphonate into biodegradable microspheres.
AB  - The aim of this work was to optimize the encapsulation of a third generation
      bisphosphonate (risedronate sodium RS) into polylactide-co-glycolide (PLGA)
      microspheres using a double emulsion technique for implant purposes. Microspheres
      were prepared by w/o/w double emulsion technique using PLGA in the ratio of 50:50
      and 75:25. Critical process parameters namely: polymer type and amount, drug
      amount and internal aqueous phase volume ratio were evaluated for their effect on
      entrapment efficiency (EE%) of RS. Microspheres were characterized for their
      entrapment efficiency, morphology and particle size by UV spectrophotometry,
      scanning electron microscopy, and laser diffraction respectively. A 2(4) full
      factorial design was used for model production. High EE% exceeding 80% were
      obtained through the manipulation of the previously mentioned factors.
      Microparticles showed smooth surface with few pores and a size ranging from 1-6
      um. The factorial mathematical model was validated by check point analysis
      revealing good agreement between actual and predicted values. PLGA microspheres
      successfully encapsulated RS at high levels with suitable size and morphology
      suggesting their potential use in the treatment of bone diseases as injectable
      implants.

PMID- 20799366
TI  - Intranasal clobazam delivery in the treatment of status epilepticus.
AB  - The aim of the present investigation was to prepare and characterize clobazam
      mucoadhesive microemulsion (CZMME) to assess brain drug uptake and protection
      against pentylenetetrazole (PTZ)-induced convulsions in mice. Clobazam
      microemulsion (CZME) and CZMME were prepared by titration method and
      characterized. Brain uptake and pharmacokinetic parameters were calculated from
      drug concentration in mice brain versus time plots following intranasal
      administration of radiolabeled CZME and CZMME, intravenous and intranasal
      administration of radiolabeled clobazam solution. Gamma scintigraphy imaging of
      rabbit brain following intranasal administration was performed. Formulations were
      investigated for the onset of seizures in PTZ-challenged mice. Brain targeting
      efficiency and direct nose-to-brain transport percentage for mucoadhesive
      microemulsion suggested an improved brain uptake following intranasal
      administration. The findings were supported by gamma scintigraphy images. Delay
      in onset of PTZ-induced seizures with CZMME compared with positive control and
      placebo-treated groups confirmed the improved brain uptake. However, extensive
      animal studies followed by clinical trials are necessary to develop a product
      suitable for emergencies of acute seizures in status epilepticus and patients
      suffering from drug tolerance and hepatic impairment on long-term use in
      treatment of epilepsy, schizophrenia, and anxiety.

PMID- 20799367
TI  - Thermosensitive hydrogels composed of hyaluronic acid and gelatin as carriers for
      the intravesical administration of cisplatin.
AB  - The aim of this work was to evaluate the use of thermosensitive hydrogels for
      intravesical cisplatin delivery into the bladder. Poly(N-isopropylacrylamide)
      (PNIPAM) was grafted onto hyaluronic acid (HA) to synthesize an HPN copolymer,
      which was further grafted with gelatin to form an HPNG copolymer. A 3%
      concentration of HPN and HPNG was sufficient to exert a thermosensitive response,
      whereas a concentration of 8% was needed for PNIPAM to form the hydrogel. The
      physicochemical and drug delivery properties were examined by scanning electron
      microscopy (SEM), the lower critical solution temperature (LCST), hydration
      ratio, and in vitro cisplatin release. The incorporation of HA and gelatin
      produced a different microstructure compared to the parent PNIPAM hydrogel.
      Gelatin conjugation increased the fibrous structure in the matrix. The LCSTs of
      PNIPAM, HPN, and HPNG were 32.3, 32.0, and 30.7 degrees C, respectively. The
      copolymers showed an eightfold increase in the hydration capacity compared to
      PNIPAM, with no significant difference in values between HPN and HPNG. The
      release of cisplatin from an aqueous solution (control) was nearly complete after
      8 h, compared to 85, 80, and 52% release from PNIPAM, HPN, and HPNG,
      respectively. In vivo evaluation of cisplatin levels in bladder tissues was
      performed following intravesical instillation in rats. When the dwell time was
      extended to 6 h, PNIPAM showed a sevenfold enhancement in the drug concentration
      in the bladder wall. HPNG also showed a twofold increase in the drug
      concentration. The administration of cisplatin by the HPN carrier did not change
      the drug accumulation compared to the control. Confocal laser scanning
      microscopic results confirmed the trend of drug absorption from various systems.
      A histological examination showed no adverse change in the urothelium with HPN or
      HPNG application. PNIPAM caused partial desquamation of umbrella cells. The
      thermosensitive hydrogels prepared in this study may be promising carriers for
      targeted drug delivery to the bladder.

PMID- 20799368
TI  - Monitoring of the secondary drying in freeze-drying of pharmaceuticals.
AB  - This paper is focused on the in-line monitoring of the secondary drying phase of
      a lyophilization process. An innovative software sensor is presented to estimate
      reliably the residual moisture in the product and the time required to complete
      secondary drying, that is, to reach the target value of the residual moisture or
      of the desorption rate. Such results are obtained by coupling a mathematical
      model of the process and the in-line measurement of the solvent desorption rate
      and by means of the pressure rise test or another sensors (e.g., windmills, laser
      sensors) that can measure the vapor flux in the drying chamber. The proposed
      method does not require extracting any vial during the operation or using
      expensive sensors to measure off-line the residual moisture. Moreover, it does
      not require any preliminary experiment to determine the relationship between the
      desorption rate and residual moisture in the product. The effectiveness of the
      proposed approach is demonstrated by means of experiments carried out in a pilot
      scale apparatus: in this case, some vials were extracted from the drying chamber
      and the moisture content was measured to validate the estimations provided by the
      soft-sensor.

PMID- 20799369
TI  - Activation of calcium/calmodulin-dependent protein kinase IV and peroxisome
      proliferator-activated receptor gamma coactivator-1alpha signaling pathway
      protects against neuronal injury and promotes mitochondrial biogenesis in the
      hippocampal CA1 subfield after transient global ischemia.
AB  - Delayed neuronal cell death occurs in the vulnerable CA1 subfield of the
      hippocampus after transient global ischemia (TGI). We demonstrated previously,
      based on an experimental model of TGI, that the significantly increased content
      of oxidized proteins in hippocampal CA1 neuron was observed as early as 30 min
      after TGI, followed by augmentation of PGC-1alpha expression at 1 hr, as well as
      up-regulation of mitochondrial uncoupling protein 2 (UCP2) and superoxide
      dismutases 2 (SOD2). Using the same animal model, the present study investigated
      the role of calcium/calmodulin-dependent protein kinase IV (CaMKIV) and PGC
      1alpha in delayed neuronal cell death and mitochondrial biogenesis in the
      hippocampus. In Sprague-Dawley rats, significantly increased expression of
      nuclear CaMKIV was noted in the hippocampal CA1 subfield as early as 15 min after
      TGI. In addition, the index of mitochondrial biogenesis, including a
      mitochondrial DNA-encoded polypeptide, cytochrome c oxidase subunit 1 (COX1), and
      mitochondrial number significantly increased in the hippocampal CA1 subfield 4 hr
      after TGI. Application bilaterally into the hippocampal CA1 subfield of an
      inhibitor of CaMKIV, KN-93, 30 min before TGI attenuated both CaMKIV and PGC
      1alpha expression, followed by down-regulation of UCP2 and SOD2, decrease of COX1
      expression and mitochondrial number, heightened protein oxidation, and enhanced
      hippocampal CA1 neuronal damage. This study provides correlative evidence for the
      neuroprotective cascade of CaMKIV/PGC-1alpha which implicates at least in part
      the mitochondrial antioxidants UCP2 and SOD2 as well as mitochondrial biogenesis
      in ischemic brain injury.

PMID- 20799370
TI  - Self-management strategies used during flares of rheumatoid arthritis in an
      ethnically diverse population.
AB  - OBJECTIVES:  Effective management of flares of rheumatoid arthritis (RA) can
      improve symptoms and may delay disease progression. The practice of
      rheumatologists in managing a flare has been studied, but patients' experiences
      of, and responses to, disease flares remain poorly defined. This study aimed to
      address this issue. METHODS:  Semi-structured interviews were conducted with 21
      patients from an ethnically diverse population who had suffered a recent RA
      flare. Open questions were asked regarding patients' definitions of a flare,
      causal attribution, self-management strategies, their triggers to consult health
      professionals, and the information they had received about RA flares from health
      professionals. Transcripts were studied using the grounded theory approach to
      identify themes. RESULTS:  Flares were usually described as worsening joint pain
      and swelling. Over-use of joints was identified as the most common cause of a
      flare, and commonly used self-management strategies included rest, gentle
      exercise and warming the joints. There was some variation in causal attribution
      and self-management with ethnicity. CONCLUSIONS:  This study identified a link
      between causal attribution of flares and the resultant self-management
      strategies. A perceived trigger of the flare in some patients formed a focus for
      their self-management strategies, whereas those who could not identify a cause
      aimed mainly to alleviate symptoms. A better understanding of patients'
      perspective in the context of disease flares will allow the development of
      educational programmes to facilitate more effective self-management of this
      important manifestation of disease.

PMID- 20799371
TI  - Real-time MRI at a resolution of 20 ms.
AB  - The desire to visualize noninvasively physiological processes at high temporal
      resolution has been a driving force for the development of MRI since its
      inception in 1973. In this article, we describe a unique method for real-time MRI
      that reduces image acquisition times to only 20 ms. Although approaching the
      ultimate limit of MRI technology, the method yields high image quality in terms
      of spatial resolution, signal-to-noise ratio and the absence of artifacts. As
      proposed previously, a fast low-angle shot (FLASH) gradient-echo MRI technique
      (which allows for rapid and continuous image acquisitions) is combined with a
      radial encoding scheme (which offers motion robustness and moderate tolerance to
      data undersampling) and, most importantly, an iterative image reconstruction by
      regularized nonlinear inversion (which exploits the advantages of parallel
      imaging with multiple receiver coils). In this article, the extension of
      regularization and filtering to the temporal domain exploits consistencies in
      successive data acquisitions and thereby enhances the degree of radial
      undersampling in a hitherto unexpected manner by one order of magnitude. The
      results obtained for turbulent flow, human speech production and human heart
      function demonstrate considerable potential for real-time MRI studies of dynamic
      processes in a wide range of scientific and clinical settings.

PMID- 20799372
TI  - Engineering homochiral metal-organic frameworks for heterogeneous asymmetric
      catalysis and enantioselective separation.
AB  - Owing to the potential applications in technological areas such as gas storage,
      catalysis, separation, sensing and nonlinear optics, tremendous efforts have been
      devoted to the development of porous metal-organic frameworks (MOFs) over the
      past ten years. Homochiral porous MOFs are particularly attractive candidates as
      heterogeneous asymmetric catalysts and enantioselective adsorbents and separators
      for production of optically active organic compounds due to the lack of
      homochiral inorganic porous materials such as zeolites. In this review, we
      summarize the recent research progress in homochiral MOF materials, including
      their synthetic strategy, distinctive structural features and latest advances in
      asymmetric heterogeneous catalysis and enantioselective separation.

PMID- 20799373
TI  - Stress, coping, and hope.
AB  - Hope is discussed in many literatures and from many perspectives. In this essay
      hope is discussed from the vantage of psychology and stress and coping theory.
      Hope and psychological stress share a number of formal properties: both are
      contextual, meaning-based, and dynamic, and both affect well-being in difficult
      circumstances. Two assumptions underlie this essay: (1) hope is essential for
      people who are coping with serious and prolonged psychological stress; and (2)
      hope is not a perpetually self-renewing resource; it has peaks and valleys and is
      at times absent altogether. The relationship between hope and coping is dynamic
      and reciprocal; each in turn supports and is supported by the other. This
      relationship is illustrated with two adaptive tasks common across situations that
      threaten physical or psychological well-being-managing uncertainty and coping
      with a changing reality. The essay describes ways in which coping fosters hope
      when it is at low ebb as well as ways in which hope fosters and sustains coping
      over the long term.

PMID- 20799374
TI  - Ethnic differences in participation in prenatal screening for Down syndrome: a
      register-based study.
AB  - OBJECTIVE: To assess ethnic differences in participation in prenatal screening
      for Down syndrome in the Netherlands. METHODS: Participation in prenatal
      screening was assessed for the period 1 January 2009 to 1 July 2009 in a defined
      postal code area in the southwest of the Netherlands. Data on ethnic origin,
      socio-economic background and age of participants in prenatal screening were
      obtained from the Medical Diagnostic Centre and the Department of Clinical
      Genetics. Population data were obtained from Statistics Netherlands. Logistic
      regression models were used to assess ethnic differences in participation,
      adjusted for socio-economic and age differences. RESULTS: The overall
      participation in prenatal screening was 3865 out of 15 093 (26%). Participation
      was 28% among Dutch women, 15% among those from Turkish ethnic origin, 8% among
      those from North-African origin, 15% among those from Aruban/Antillean origin and
      26% among women from Surinamese origin. CONCLUSIONS: Compared to Dutch women,
      those from Turkish, North-African, Aruban/Antillean and other non-Western ethnic
      origin were less likely to participate in screening. It was unexpected that women
      from Surinamese origin equally participated. It should be further investigated to
      what extent participation and non-participation in these various ethnic groups
      was based on informed decision-making.

PMID- 20799375
TI  - Aiming at multidisciplinary consensus: what should be detected in prenatal
      diagnosis?
AB  - OBJECTIVE: To determine expert consensus on which chromosomal abnormalities
      should and should not be detected in prenatal diagnosis, and for which
      abnormalities disagreement remains after structured discussion. METHODS: An
      expert panel of 24 prenatal experts (8 clinical cytogeneticists, 8 clinical
      geneticists and 8 obstetricians) rated 15 chromosomal abnormalities sampled from
      a nationwide study on rapid aneuploidy detection (RAD). In two individual
      anonymous rating rounds and one group meeting, the participants rated PRO or
      AGAINST detection and stated their main argument. The 15 chromosomal
      abnormalities were described in detail by a stylized vignette containing an
      obstetrical history, the indication for prenatal diagnosis and the range of
      possible outcomes of the chromosomal abnormality. Consensus was defined to be
      present if at least 80% of the experts agreed. RESULTS: Consensus was reached in
      12 out of 15 cases. In ten cases, there was agreement PRO detection and in two
      cases experts agreed AGAINST detection. At the end of the third round, dissensus
      remained on three abnormalities. CONCLUSION: Experts largely agreed on detecting
      chromosomal abnormalities with severe consequences and AGAINST detection in case
      of irrelevant clinical consequences. For chromosomal abnormalities with mild or
      uncertain outcomes, dissensus remained. None of the currently available tests
      corresponds to these demands.

PMID- 20799376
TI  - Mechanism for the direct synthesis of tryptophan from indole and serine: a useful
      NMR technique for the detection of a reactive intermediate in the reaction
      mixture.
AB  - The reaction mechanism for the biomimetic synthesis of tryptophan from indole and
      serine in the presence of Ac(2)O in AcOH was investigated. Although the time
      course (1)H-NMR spectra of the reaction of 5-methoxyindole with N-acetylserine
      were measured in the presence of (CD(3)CO)(2)O in CD(3)CO(2)D, the reactive
      intermediate could not be detected. This reaction was conducted without 5
      methoxyindole in order to elucidate the reactive intermediate, but the
      intermediate could not be isolated from the reaction mixture. Since the
      intermediate would be expected to have a very short life time, and therefore be
      very difficult to detect by conventional analytical methods, the structure of the
      intermediate was elucidated using a 2D-NMR technique, diffusion-ordered
      spectroscopy (DOSY). Two intermediates were detected and confirmed to be 2-methyl
      4-methyleneoxazol-5(4H)-one and 2-methyl-4-hydroxymethyloxazol-5(4H)-one. The
      present results demonstrated that DOSY is a powerful tool for the detection of
      unstable intermediates.

PMID- 20799377
TI  - It's not all Alzheimer's.  Sorting out cognitive changes.

PMID- 20799378
TI  - Promising research for advanced prostate cancer.

PMID- 20799379
TI  - Meningioma.  Understanding this usually benign brain tumor.

PMID- 20799380
TI  - Is it possible to be allergic to metal fillings or crowns on teeth?

PMID- 20799381
TI  - What's hyperbaric oxygen therapy?  What's it used for?

PMID- 20799382
TI  - Special report.  Deciphering dementia.  Loss of brain function can be caused by
      many disorders.

PMID- 20799383
TI  - Some questions provoked by a chronic headache (with mixed migraine and cluster
      headache features) in a woman with a pineal cyst. Answers from a literature
      review.
AB  - The main known function of the pineal gland in humans is the production of
      melatonin. Benign cysts of the gland have been related to headache, although the
      mechanism of production of this assumed clinical manifestation has not been
      clearly determined, due to the lack of large prospective studies. The question is
      complicated by the fact that pineal cysts are frequently found on brain magnetic
      resonance imaging. Much has been published about the possible role of benign
      pineal cysts in the pathophisiology of headaches and the potential of melatonin
      in headache therapy, as well as in other disorders. The aim of this article is to
      review the current state of the subject. We have tried to place accurately the
      relation between headache and pineal cysts based on the available evidence, as
      well as the actual role of melatonin in physiology and pharmacology, more
      specifically in headache therapy. We include a clinical case to illustrate the
      subject.

PMID- 20799384
TI  - Proceedings of the 14th Scientific Symposium Diabetes Mellitus Today. 13-14
      November, 2008, Madrid, Spain.

PMID- 20799386
TI  - Abstracts of the 16th European Bioenergetics Conference, 17-22 July 2010, Warsaw,
      Poland.

PMID- 20799385
TI  - Proceedings of the 2009 Iverson Bell Symposium: Recruiting and Retaining
      Minorities in Veterinary Education.

PMID- 20799387
TI  - HPV vaccination recommended for 9- to 26-year-old male patients.

PMID- 20799389
TI  - From the editors.

PMID- 20799388
TI  - Validation of measures of satisfaction with and impact of continuous and
      conventional glucose monitoring.
AB  - BACKGROUND: The evaluation of patient-reported outcomes (e.g. impact,
      satisfaction) is important in trials of continuous glucose monitoring (CGM). We
      evaluated psychometric properties of the CGM Satisfaction Scale (CGM-SAT) and the
      Glucose Monitoring Survey (GMS). METHODS: CGM-SAT is a 44-item scale on which
      patients (n=224) or parents (n=102) rated their experience with CGM over the
      prior 6 months. GMS is a 22-item scale on which patients (n=447) or parents
      (n=221) rated the blood glucose monitoring system they were using (home glucose
      meter with or without CGM) at baseline and 6 months. RESULTS: The alpha
      coefficient for the CGM-SAT was > or = 0.94 for all respondents and for the GMS
      was > or = 0.84 for all respondents at baseline and 6 months. Parent-youth
      agreement was 0.52 for the CGM-SAT at 6 months and 0.24 and 0.20 for the GMS at
      baseline and 6 months for the Standard Care Group, respectively. Test-retest
      reliability of the GMS at 6 months for controls was r=0.76 for adult patients,
      0.63 for pediatric patients, and 0.43 for parents. Factor analysis isolated
      measurement factors for the CGM-SAT labeled Benefits of CGM and Hassles of CGM,
      accounting for 33% and 9% of score variance, respectively. For the GMS, two
      factors emerged: Glucose Control and Social Complications, accounting for 28% and
      9% of variance, respectively. Significant correlations of CGM-SAT with frequency
      of CGM use between 6 months and baseline and GMS with frequency of conventional
      daily self-monitoring of blood glucose at baseline support their convergent
      validity. CONCLUSIONS: The CGM-SAT and GMS are reliable and valid measures of
      patient-reported CGM outcomes.

PMID- 20799391
TI  - [Proceedings of the 3rd International Congress on Hemodynamic Monitoring. 19-20
      February 2010, Dubrava, Zagreb].

PMID- 20799390
TI  - Population genetics: Breaking down hybrids.

PMID- 20799392
TI  - Antithrombotic medications and recurrent miscarriage.

PMID- 20799393
TI  - Cost consciousness and medical education.

PMID- 20799394
TI  - Cost consciousness and medical education.

PMID- 20799396
TI  - Proceedings from the XIII International Conference on Electron Microscopy.

PMID- 20799395
TI  - Cost consciousness and medical education.

PMID- 20799397
TI  - [Delayed influenza mortality in elderly persons].
AB  - AIM: Analysis of influenza morbidity and mortality including delayed mortality as
      well as study of the association between increased mortality in elderly and
      influenza incidence. MATERIALS AND METHODS: Epidemiologic methods of research as
      well as reporting forms No. 2 and C51 for Moscow for the period 1999-2005 were
      used. Analysis was performed for 28,801,565 cases of influenza illness as well as
      for 41,310 fatal cases, of which 6048 cases due to cardiovascular and respiratory
      diseases were extracted. Retrospective epidemiologic analysis of perennial and
      within-year incidence of influenza and mortality due to mentioned diseases in
      Moscow was performed. Correlation analysis was done using Spearman rank
      correlation coefficient and Pearson correlation coefficient. RESULTS: Delayed
      mortality concept was introduced. Existence of delayed mortality after influenza
      illness in persons >60 year old with ischemic heart disease, acute myocardial
      infarction and cerebrovascular disease was proved. It was established that
      vaccination against influenza in persons aged >60 years with underlying
      cardiovascular diseases during epidemic season could prevent 246 deaths each
      year. CONCLUSION: Delayed mortality was detected only in patients with
      cardiovascular diseases, whereas in patients with respiratory diseases direct
      complications due to influenza developed. Influenza immunization of elderly
      persons could yield marked economic effect as cost of treatment of one case of
      acute myocardial infarction or attack of cerebrovascular disease is significantly
      higher than cost of vaccination.

PMID- 20799398
TI  - [Anthrax cattle burial grounds in Russia and their biosafety].
AB  - AIM: To develop standard operating procedure for assessment level of biohazard
      for population living near existing cattle burial grounds. MATERIALS AND METHODS:
      Development of standard operating procedure for assessment of biosafety of cattle
      burial grounds was performed on the basis of regulatory documents and regional
      field practical experience. Assessment of biohazard level of anthrax cattle
      burial grounds was performed in 5 regions choosen on the basis of certain
      criteria. Total number of samples taken was 762. RESULTS: Rating of federal
      districts according to number of permanently problematic on anthrax places was
      composed. It was determined that maximal number of permanently problematic on
      anthrax places was active during time period until 1950. Agent of anthrax was not
      detected in studied samples either as spores or vegetative forms and soil was
      categorized as "clean" on all indicators. CONCLUSION: It was determined that
      conditions of burial of cattle fallen due to anthrax and their maintenance rules
      are followed in 5 places. All cattle burial grounds are located inside towns'
      borders or adjoin to areas of existing or planned apartment blocks.

PMID- 20799399
TI  - [Immunovac-VP4 vaccine used in complex allergen-specific immunotherapy of
      patients with hay fever].
AB  - AIM: Assessment of clinical and immunological effects of use of bacterial
      therapeutic polycomponent vaccine Immunovac-VP4 for allergen-specific
      immunotherapy (ASIT) of hay fever. MATERIALS AND METHODS: Five doses of Immunovac
      VP4 vaccine consisted of antigens of opportunistic bacteria was used and
      administered by nasal-oral route. ASIT was performed with standard water-saline
      solution of allergens according to defined schedule. Sixty-nine patients with
      season rhinoconjunctivitis, asthma and their combinations were included in the
      study and divided to two groups. Skin scarification test was performed, total
      level of serum IgE, IgG4 and IgE to pollen allergens were measured by ELISA.
      Also, questionnaire was sent to patients yearly. RESULTS: Administration of
      bacterial therapeutic vaccine Immunovac-VP4 before start of ASIT resulted in
      marked clinical and immunological effect. In group of patients receiving
      combination therapy compared to control group, 8.5 times lower incidence of acute
      respiratory infections was registered. According to results of analysis of
      patients' questionnaires after 7 years, effectiveness of therapy was 90% that
      points to achievement of prolonged remission after completion of ASIT course.
      CONCLUSION: Utilization of natural ligands of Toll-like receptors is a
      perspective direction for development of new immunotherapeutic strategies for
      treatment of allergic diseases.

PMID- 20799400
TI  - [Effect of Yersinia pestis EV 76 lypopolysaccharides with different levels of
      toxicity on dynamics of TNF-alpha and INF-gamma synthesis by human monocytes].
AB  - AIM. To study dynamics of synthesis of TNF-alpha and INF-gamma by cell line U-937
      human monocytes under the effect of Yersinia pestis EV 76 lypopolysaccharides
      (LPS) with different levels of toxicity: original LPS28 and LPS37 as well as
      their conformationally--changed variants with enhanced toxicity--complex of LPS
      with murine toxin (MT) of Y. pestis, and LPS modified by biologicall active
      compound (BAC) obtained from human erythrocytes. MATERIALS AND METHODS: Using
      phenol method, LPS were obtained from Y. pestis EV 76 cells grown at 28 and 37
      degrees C. Production of cytokines was measured by ELISA. RESULTS: It was shown
      that original and modified forms of LPS28 and LPS37 induce synthesis of both TNF
      alpha and INF-gamma by human monocytes. Expression of genes for two ways of
      synthesis of these cytokines points to activation and transmission of signal
      induced by all studied forms of Y. pestis EV 76 LPS through TLR4. Levels of
      activity of MyD88-dependent and MyD88-independent signaling pathways are
      different and depend from chemical structure of LPS28 and LPS37, conformation of
      their modified forms and duration of their exposition with monocytes. Dynamics
      ofcytokine synthesis corresponds to response of synergized TLR on activation with
      profound agonistic/antagonistic effect. CONCLUSION: It was determined that
      conformational modifications of Y. pestis EV76 LPS occurring due to effect of MT
      and BAC accompanied by quantitative, qualitative and temporal changes of TNF
      alpha and INF-gamma synthesis by human monocytes and correlate with increase of
      their toxic properties.

PMID- 20799401
TI  - [Improvement of method of Coxiella burnetii detection in biological material
      based on groEL gene amplification].
AB  - AIM: Improvement of PCR for detection of Coxiella burnetii in field material by
      development of set of primers for amplification of groEL gene fragment. MATERIALS
      AND METHODS: C. burnetii strains, samples from organs of wild rodents and
      laboratory animals, blood of healthy donors and laboratory animals. Methods of
      DNA isolation, PCR, and electrophoresis in agarose gel were used. RESULTS:
      Nucleotide sequences of primers amplifying groEL gene fragment, which could
      increase specificity of PCR during work with field material were proposed.
      CONCLUSION: Obtained data open perspective for using this method for detection of
      C. burnetii in environment.

PMID- 20799402
TI  - [Identification of Mycoplasma in patients with suspected prostate cancer].
AB  - AIM: Tests for Mycoplasma hominis, M. genitalium, Ureaplasma urealyticum in males
      with suspected prostate cancer. MATERIALS AND METHODS: Identification of
      mycoplasms was performed in prostate tissue samples using universal PCR as well
      as in serum samples of patients with suspected prostate cancer using ELISA for
      detection of IgG to M. hominis. Two hundred and fifty samples from each lobe of
      prostate were obtained from 125 patients with suspected prostate cancer by
      transrectal polyfocal biopsy. Blood samples were drawn from the same patients for
      ELISA. RESULTS: Out of 125 patients with suspected prostate cancer, 20.5% were
      positive for Mycoplasma by PCR. Between studied species, only M. hominis was
      found in big proportion of analyzed samples. Out of 118 serum samples, 30.5% were
      positive for IgG to M. hominis in ELISA. CONCLUSION: Fact of presence of
      Mycoplasma species in tissue of prostate was established in 20.5% pf patients
      with suspected prostate cancer. Obtained results show that M. hominis is
      frequently infects prostate tissue and that this infection was more common in
      patients with high grade prostatic interstitial neoplasia and prostate cancer
      than in patients with benign changes of prostate tissue or in persons without
      prostate disease. This allows to suggest that infection with M. hominis could
      play an important role in development of cancer.

PMID- 20799403
TI  - [Study of expression of contact-dependent secretion systems in Vibrio cholerae on
      the model of Dictyostelium discoideum].
AB  - AIM: To detect T3SS and T6SS genes in Vibrio cholerae genomes and assessment of
      resistance of strains with different genotype characteristics to ingestion by
      Dictyostelium discoideum amoeba. MATERIALS AND METHODS: One hundred thirty-five
      toxigenic and non-toxigenic strains of Echolerae O1, O139, and non-O1/non-O139
      were studied by PCR and on Dictyostelium discoideum model. RESULTS: T3SS cluster
      of genes was detected in several non-toxigenic representatives of 01 and non
      O1/non-O139 serogroups. All toxigenic vibrios except one strain belonging to non
      O1/ non-O139 serogroup lack this cluster. T6SS genes were presented in all
      studied strains although far from allofthem contained sequence coding ACD-domain
      of vgrG1 gene product--key effector of T6SS. Susceptibility of vibrios to
      ingestion by amoeba did not depend from presence of T3SS genes. Only strains with
      genetic determinants ACD-vgrG1 together with pathogenicity locus VPI were
      resistant to ingestion, all others were susceptible. CONCLUSION: D. discoideum
      model is adequate for study of expression of T6SS but not T3SS in V. cholerae.
      The latter is rather needed for colonization of intestine than for antagonistic
      activity against protozoa in external environment. Expression of T6SS is
      characteristic for many non-toxigenic strains of V. cholerae, whereas use of
      contact-dependent secretion is unlikely necessary for majority of toxigenic
      strains.

PMID- 20799404
TI  - [Influenza vaccination during pregnancy].
AB  - Review covers the problem of influenza vaccination during pregnancy, which
      according to WHO's experts conclusion represents a risk group. It is known that
      complications due to influenza develop significantly more frequently especially
      in case of presence of chronic diseases. It has been scientifically proven that
      vaccination against influenza is safe and effective for prevention of
      complications due to infection for both mother and fetus. Children born to
      mothers vaccinated during pregnancy are passively protected during first 6 months
      of life. It was shown that despite the potential value of influenza vaccines as a
      measure for reducing morbidity in mother and fetus, coverage of influenza
      immunization in pregnant women continues to be lower than 10%.

PMID- 20799405
TI  - [Interferons and other cytokines in rheumatic diseases].
AB  - With the growth of rheumatic morbidity the spectrum of medicines for its
      management needs to be extended. Selected aspects of etiology and clinical course
      of rheumatic diseases are discussed with reference to prospects of their
      application for etiopathogenetic therapy.

PMID- 20799406
TI  - [Plasma antioxidant activity--a test for impaired biological functions of
      endoecology, exotrophy, and inflammation reactions].
AB  - The authors discuss the diagnostic value of a test for total serum antioxidant
      activity determined by an electrochemistry method on a liquid chromatograph
      (without a column), by using an amperometric detector, as well as the composition
      of the endogenously synthesized hydrophilic and hydrophobic acceptors of reactive
      oxygen species (ROS). Uric acid is a major hydrophilic acceptor of ROS; monoenic
      oleic fatty acid acts as its major lipophilic acceptor. The constant determined
      by the authors for of 03 oleic acid oxidation during automatic titration in the
      organic medium is an order of magnitude higher than that for alpha-tocopherol,
      beta-carotene and linoleic fatty acid; its concentration is also an order of
      magnitude higher. In oxidative stress, the adrenal steroid hormone
      dehydroepiandrosterone initiates oleic acid synthesis via expression of palmitoyl
      elongase and steatoryl desaturase. In early steps of phylogenesis in primates,
      spontaneous mutation resulted in ascorbic acid synthesis gene knockout;
      phylogenetically, further other mutation knocked out the gene encoding the
      synthesis of uricase and the conversion of uric acid to alantoin. In primates,
      uric acid became not only a catabolite of purine bases in vivo, but also the
      major endogenous hydrophilic acceptor of ROS. This philogenetic order makes it
      clear why the epithelium in the proximal nephron tubule entirely reabsorbs uric
      acid (a catabolite?) from primary urine and then secretes it again to urine
      depending on the impairment of biological functions of endoecology (the
      intercellular medium being contaminated with biological rubbish), the activation
      of a biological inflammatory reaction, the cellular production of ROS, and the
      reduction in serum total antioxidant activity. With each biological reaction,
      there was an increase in the blood content of uric acid as a hydrophilic acceptor
      of ROS, by actively lowering its secretion into urine. Uric acid is a diagnostic
      test of inflammation, or rather compensatory anti-inflammatory response syndrome.

PMID- 20799407
TI  - [Impact of small molecules on intermolecular interactions underlying the ligand
      technologies in laboratory diagnosis].
AB  - Hydrogen peroxide has been found to have a distorting effect on the quality of
      determination of the serological markers of hepatitis B and C, transglutaminase
      antibodies: an increase in the percent of false higher (anti-HBsAg, HBeAg, anti
      HCV) and false lower (anti-HBeAg) values, and on the results of PCR-based
      diagnosis (PCR inhibition that was more pronounced especially in low viremia). A
      possibility of interference of measurement results in the blood metabolite pool
      should be taken into account in the use of high-technology methods of laboratory
      analysis. In particular, there may be changes in the detection of immunological
      and molecular biological methods in hyperpyruvatemia and hyperoxaloacetatemia,
      with elevated peroxide concentrations during pathological processes.

PMID- 20799408
TI  - [Role of an infectious factor in the pathogenesis of urolithiasis].
AB  - The paper gives the data of complex clinical and biochemical examination in 122
      urolithiasis (ULT) inpatients treated at the Urology Unit, Moscow City Clinical
      Hospital Seven, in February 2004 to January 2008. The levels of lithogenic
      substances and compounds, inhibitors and activators of lithogenesis have been
      determined. The authors show it possible to use the level of hydrolytic enzymes
      and activators of cooperative microbial sensitivity as diagnostic and prognostic
      criteria in diferent forms of ULT, which is in turn of no small importance in
      developing the science-based methods for the treatment and prevention of
      recurrent lithogenesis.

PMID- 20799409
TI  - [Metabolic processes in the body exposed to chemical pollutants].
AB  - The paper gives the results of studying the processes of free radical and
      microsomal oxidation, antioxidant defense, and energy and electrolyte metabolism
      in the workers of OAO "Salavatnefteorgsintez", one of the leading petrochemical
      plants in the Republic of Bashkortostan. The metabolic processes have been found
      to substantially change in the persons contacting a mixture of chlorinated and
      aromatic hydrocarbons under industrial conditions.

PMID- 20799410
TI  - [Information technologies in clinical cytology (a lecture)].
AB  - The lecture is devoted to the urgent problem that is to increase the quality of
      cytological diagnosis, by diminishing the subjectivism factor via introduction of
      up-to-date computer information technologies into a cytologist's practice. Its
      main lines from the standardization of cytological specimen preparation to the
      registration of a cytologist's opinion and the assessment of the specialist's
      work quality at the laboratories that successfully use the capacities of the
      current information systems are described. Information technology capabilities to
      improve the interpretation of the cellular composition of cytological specimens
      are detailed.

PMID- 20799411
TI  - [An electrosurgical tool on the basis of nanostructured dioxide zirconium
      crystals for dissection and coagulation of biological tissues].

PMID- 20799412
TI  - [Processing of dynamic images for solution of the navigation problem during
      transurethral resection of prostate gland].

PMID- 20799413
TI  - [A model impedance of cardiac pacemaker electrodes].

PMID- 20799415
TI  - Proceedings from the 15th EFIS-EJI Symposium on Signals and Signal Processing in
      the Immune System, September 2009.

PMID- 20799414
TI  - Corrigendum to "HMBA depolymerizes microtubules, activates mitotic checkpoints
      and induces mitotic block in MCF-7 cells by binding at the colchicine site in
      tubulin" [Biochem. Pharmacol. 80 (2010) 50-61].

PMID- 20799416
TI  - Niacin, fenofibrates increase benefits for statin users.  These HDL- raising,
      triglyceride-lowering drugs beat out the use of additional LDL-lowering drugs.

PMID- 20799417
TI  - Gait disturbances in older age.  The reasons are many and varied, but researchers
      agree that identifying the source and preserving mobility are primary concerns.

PMID- 20799418
TI  - Prostate cancer drugs' safety in question.  Links with heart disease and diabetes
      have resulted in FDA review of the drugs' safety.

PMID- 20799419
TI  - Interiors, intentions, and the "spirituality" of Islamic ritual practice.
AB  - The Arabic term niyya (intention) is prominent in texts of Islamic ritual law.
      Muslim jurists require niyya in the "heart" during such ritual duties as prayer,
      fasting, and pilgrimage. Western scholars often treat niyya as a "spiritual"
      component of Islamic ritual. Muslim jurists, however, consistently treat niyya as
      a formal, taxonomic matter, a mental focus that makes a given act into the
      specific named duty required by religious law. Although the effort to thrust
      niyya into a "spiritual" role is meant to defend Islam from charges of "empty
      ritualism," it subtly reinforces the characterization of Islam as rigidly
      legalistic. Much scholarship on niyya belies the scholars' own definition of
      "proper religion" centered on an inner, individual, nonmaterial dimension of the
      self. Instead of trying to wash away the formalism of niyya, I argue that
      scholars ought to recognize that such embodied practices are properly religious
      rather than spiritually defective.

PMID- 20799420
TI  - Free will and determinism in first Isaiah: secular hermeneutics, the poetics of
      contingency, and Emile Durkheim's Homo duplex.
AB  - Are human beings the sovereign authors of their own thoughts and actions? Or are
      thought and action determined by external forces beyond their comprehension and
      control? For the biblical document known to exegetes as First Isaiah (chapters 1
      39 of the Book of Isaiah) the answer to both queries seems to be yes. In this
      article various solutions are advanced to explain why this text equivocates on
      the question of free will and determinism. One possibility is that the document's
      collective, transhistorical composition may have scrambled its once coherent
      message beyond all recognition. Following Emile Durkheim's discussions of homo
      duplex, it will also be suggested that First Isaiah's confusion may be a
      manifestation of a deeper contradiction inherent to human consciousness-one that
      thus recurs across sociological time and space. Both solutions are united by
      their rejection of traditional theological approaches that have been brought to
      bear on First Isaiah and the Hebrew Bible in general. It is the movement away
      from such apologetic exegesis that characterizes the inchoate interpretive
      orientation that I call "secular hermeneutics."

PMID- 20799421
TI  - Good wives, family protectors: writing Jain laywomen's memorials.
AB  - While Jain religious models of virtue articulate the renouncer as the focus of
      virtue, Jains likewise participate in the western Indian discourse of women's
      virtue, which centers around the dedicated wife (pativrata) and the virtuous
      woman (sati). The parole of virtue in Jain dedicatory memorials can be seen as
      explicitly gendered; lay Jains are represented as the great patron or the
      dedicated wife. For Jain laymen who cannot be represented as great patrons, there
      is no langue to use to represent them. For Jain laywomen, the discourse of satis
      is invoked to frame the woman as virtuous and worthy of celebration-even in those
      memorials where women participate in the great patron model. These memorials are
      a place to examine how the telling of women's lives serves as a testing ground
      for competing ideologies and illustrates the patterns of negotiation between
      ideologies based on religious identity and gender.

PMID- 20799422
TI  - The Jewish refugee children from Europe in the eyes of the American press and
      public opinion 1934-1945.
AB  - Between 1934-1945 approximately 1000 unaccompanied Jewish children, refugees from
      Nazism, reached the United States. These were but a fraction of the total number
      of Jewish refugees who reached the USA during this period. Yet the Issue of child
      refugees differed from that of adults in several ways and therefore received
      separate mention in the American press. This article charts and analyzes the
      press coverage of the refugee child issue during six chronological periods 1934
      1938 and the arrival and acclimatization of the first child refugees from
      Germany, late 1938 - Kristallnacht and the aroused consciousness of the plight of
      persecuted children in Germany, 1939 - the Wagner-Rogers Bill to permit the extra
      quota entry of 20, 000 children from Germany into the United States; 1940 - the
      evacuation of British children to the United States and the furor over the use of
      American "Mercy Ships"; 1941 -1944 - the arrival of Central European refugee
      children who had found temporary refuge in France, Spain and Portugal; 1945 - the
      repatriation of evacuees and the reunion of refugee children with their surviving
      parents

PMID- 20799424
TI  - From Haeckel to Hackethal: lessons from Nazi medicine for students and
      practitioners of medicine.
AB  - In discussing such issues as euthanasia and eugenics there has been no lack of
      oblique references to Nazi medicine and the Nuremberg Trials. It is as if the
      impact of Nazi medicine on medical ethics has been most pronounced in its
      rhetoric, and regrettably also in inapt comparisons Is it possible at all to
      profitably apply the Nazi analogy to the problems of normal medicine? The
      thousand threads which linked the medical crimes inside the camps with the
      conduct of "innocent" doctors, nurses, civil administrators etc. outside, have
      been subjected to new scrutiny during the past decade. The results of these
      explorations are highly significant. They run the whole gamut from wishful
      Ignorance and timorous acquiescence to deliberate cooperation with the Nazi
      health policy of many officials and citizens. The silence of the outside world
      allowed the "few" perpetrators of medical crimes to have their way. Normal
      medicine has many important lessons to learn from this passivity and compliance
      of doctors and the public. This topic ought to be included in obligatory courses
      and examinations of medical ethics.

PMID- 20799423
TI  - A study of the readiness of Jewish/Israeli students in the health professions to
      authorize and execute involuntary mass euthanasia of "severely handicapped"
      patients.
AB  - The responses of 92 Jewish/Israeli students in the health professions in Israel
      were studied in the context of a projected future situation where the subjects
      would be working as physicians/psychologists/social workers, first in a
      developing country somewhere in Africa, and then, in the second experimental
      scenario, at a well-known treatment institution in the center of Israel. A
      successive series of contraints were described that led to a scarcity of
      resources, in which context the health authorities considered it advisable first
      to limit and then to curtail the treatment of the severebly handicapped who could
      benefit least from treatment, and as the situation became more severe to
      implement a program of involuntary mass euthanasia. Although an eithical point of
      view would call for zero participation in the policies which would bring about
      dealths of patients, it had been predicted that as many as 15% of the subjects
      would agree to curtailing treatment, 5% to participate in planning involunary
      mass euthanasia, and 2% to execute the euthanasia themselves. However, the
      results were that in African 39% agreed to curtail treatment, 17% to plan
      euthanasia, and 11% them selves to terminate the patients' lives; in Israel the
      corresponding figures were 38%, 12%, and 9% - the differences between Africa and
      Israel were not significant. The study is seen as contributing to emerging
      knowledge (in the Milgram tradition) of the widespread availability of human
      beings to undertake policies which harm, hurt and kill other human beings when
      instructed to do so by a policy directive.

PMID- 20799426
TI  - Changing thought patterns may help overcome depression.  Focusing on how patients
      think rather than how they behave helps patients with even severe depression.

PMID- 20799425
TI  - "Faith, ethics and the Holocaust": the Holocaust survivor's faith and religious
      behavior and some implications for treatment.
AB  - The survivor's religious experiences, both during and after the Holocaust have
      been underexplored in the psychological literature. This essay concerns itself
      with the survivor's religious realm as it affects the psychotherapeutic process.
      it also provides a conceptual framework for helping the therapist understand the
      significance of religion in the survivor's life. When a survivor's religious
      framework, his symbolic world, can no longer "make sense" of his life, when he
      cannot recognize his own identity, his psychological world begins to crumble:
      Clinical symptoms are thus an attempt to preserve self-cohesion, self-continuity
      and self-esteem amidst a tottering symbolic world. Treatment should focus on
      helping the survivor rebuild or create new viable human meaning formations that
      support self-affirmation.

PMID- 20799427
TI  - Trouble with weight management? Portion size might do the trick. Increasing
      intake of low-density vegetables while reducing energy-dense grains and meats can
      be an effective weight management tool.

PMID- 20799428
TI  - What's the difference between aspirin and nitroglycerin for heart attack
      prevention and treatment?

PMID- 20799429
TI  - Can clinical tests detect early signs of monohemispheric brain tumors?
AB  - BACKGROUND AND PURPOSE: Prior to modern neuroimaging, neurological treatment
      decisions were based on findings obtained from patient history and clinical
      examination. Despite the availability of sophisticated neuroimaging methods, to
      identify intracranial tumors the clinical recognition of associated subtle motor
      deficits is important for practice. Precise clinical tests are particularly
      advantageous, as some tumors may remain unnoticed for many. The purpose of this
      study was to determine the sensitivity and specificity of 13 clinical tests for
      detection of subtle motor deficits in patients with unilateral brain tumors.
      METHODS: Sixty patients with unilateral brain tumors without obvious focal signs
      and 30 controls with normal magnetic resonance imaging were examined. Thirteen
      clinical maneuvers described to detect motor deficits were performed and their
      sensitivity, specificity, and positive and negative predictive values were
      estimated. RESULTS: The test with greatest sensitivity and specificity (with 95%
      confidence interval) was the Digit Quinti Sign: 0.51 (0.41-0.61) and 0.70 (0.61
      0.79), respectively. The agreement measurement among the 3 most sensitive signs
      (Digit Quinti Sign, Pronator Drifting Test, and Finger Rolling Test) was 21%. The
      Kappa index for these 3 tests indicated no significant concordance. CONCLUSIONS:
      The Digit Quinti Sign, the Pronator Drifting Test, and the Finger Rolling Test
      are simple yet very useful maneuvers that clinicians can perform at bedside. Even
      without apparent motor deficits, when present, these signs suggest that
      comprehensive investigation for intracranial neoplams should be undertaken.

PMID- 20799430
TI  - The Kinesthetic and Visual Imagery Questionnaire is a reliable tool for
      individuals with Parkinson disease.
AB  - BACKGROUND AND PURPOSE: It is not known whether individuals with Parkinson
      disease (PD) can practice movements mentally. Before this question can be
      addressed, a reliable imagery assessment tool must be established. The recently
      developed Kinesthetic and Visual Imagery Questionnaire (KVIQ) is valid for non
      disabled individuals and individuals with stroke. We have extended this work by
      examining the test-retest reliability and concurrent validity of the KVIQ in
      individuals with PD. METHODS: Eleven individuals with mild to moderate PD were
      assessed, while on medication, by the same examiner at 2 sessions (5-12 days
      apart). Test-retest reliability was measured using intraclass correlation
      coefficients (ICCs). To examine concurrent validity, KVIQ scores from the second
      session were compared with a gold standard, the revised Movement Imagery
      Questionnaire, using Spearman rank order correlation coefficients. RESULTS: There
      was no significant difference between total KVIQ scores for the test-retest
      sessions (P > 0.05). Overall, test-retest reliability of the KVIQ was good (ICC =
      0.87), and reliability of the subscale of the KVIQ for indexing visual imagery
      and kinesthetic imagery was also good (ICC = 0.82 and 0.95, respectively).
      However, the subscale indexing axial visual imagery showed less reliability (ICC
      = 0.74), suggesting that individuals with PD were not as reliable when imagining
      axial visual movements as they were for imagining limb movements. Concurrent
      validity between the second session KVIQ score and the revised Movement Imagery
      Questionnaire score (gold standard) was excellent (rho = 0.93). CONCLUSION: Our
      data support the conclusion that the KVIQ is a reliable and valid test for
      indexing mental imagery ability in individuals with PD. The KVIQ is easy to
      administer, and the movements (both real and imagined) required are appropriate
      for individuals with neuropathology. Our data suggest that the KVIQ is a good
      choice for clinicians who may wish to index motor imagery ability before
      implementing imagery as a rehabilitation intervention.

PMID- 20799431
TI  - IOM report calls for sweeping changes in cancer clinical trials.

PMID- 20799432
TI  - NIH funding 30 research projects on molecular probes.

PMID- 20799433
TI  - [Dilution in agar and Vitek 2 in Staphylococcus spp. induced resistance to
      clindamycin].

PMID- 20799434
TI  - [Pneumocystis in autopsies in the general population].

PMID- 20799437
TI  - [Culture versus polymerase chain reaction for the surveillance of enterococcus
      resistant to vancomycin].

PMID- 20799438
TI  - The female reproductive unit of ephedra (Gnetales): comparative morphology and
      evolutionary perspectives.
AB  - Morphological variation in Ephedra (Gnetales) is limited and confusing from an
      evolutionary perspective, with parallelisms and intraspecific variation. However,
      recent analyses of molecular data provide a phylogenetic framework for
      investigations of morphological traits, albeit with few informative characters in
      the investigated gene regions. We document morphological, anatomical and
      histological variation patterns in the female reproductive unit and test the
      hypothesis that some Early Cretaceous fossils, which share synapomorphies with
      Ephedra, are members of the extant clade. Results indicate that some
      morphological features are evolutionarily informative although intraspecific
      variation is evident. Histology and anatomy of cone bracts and seed envelopes
      show clade-specific variation patterns. There is little evidence for an inclusion
      of the Cretaceous fossils in the extant clade. Rather, a hypothesized general
      pattern of reduction of the vasculature in the ephedran seed envelope, probably
      from four vascular bundles in the fossils, to ancestrally three in the living
      clade, and later to two, is consistent with phylogenetic and temporal analyses,
      which indicate that extant diversity evolved after the Cretaceous-Tertiary
      boundary. Notwithstanding striking similarities between living and Cretaceous
      Ephedra, available data indicate that the Mesozoic diversity went almost entirely
      extinct in the late Cretaceous causing a bottleneck effect in Ephedra, still
      reflected today by an extraordinarily low level of genetic and structural
      diversity.

PMID- 20799439
TI  - Regulatory control and standardization of allergenic extracts. Foreword.

PMID- 20799440
TI  - Allergen source materials: state-of-the-art.
AB  - A variety of positive outcomes can be realized from validation and risk
      management activities (see Table 4). They are dependent on the participation of
      multiple functional groups including the quality unit, regulatory and legal
      affairs, engineering and production operations, research and development, and
      sales and marketing. Quality risk management is receiving increased attention in
      the area of public health, pharmacovigilance, and pharmaceutical manufacturing.
      Recent examples of its regulatory use in our industry include the assessment of
      the potential risks of transmissible spongiform encephalopathies (TSE) agents
      through contaminated products], the risks of precipitates in allergenic extracts,
      and the revision of the potency limits for standardized dust mite and grass
      allergen vaccines. Its application to allergen source material process validation
      activities allowed for a practical strategy, especially in a complex
      manufacturing environment involving hundreds of products with multiple intended
      uses. In addition, the use of tools such as FMEA was useful in evaluating
      proposed changes made to manufacturing procedures and product specifications, new
      regulatory actions, and customer feedback or complaints. The success of such a
      quality assurance programs will ultimately be reflected in the elimination or
      reduction of product failures, improvement in the detection and prediction of
      potential product failures, and increased confidence in product quality.

PMID- 20799441
TI  - BSP090--the follow-up to CREATE.

PMID- 20799442
TI  - Allergen standardization: CREATE principles applied to other purified allergens.

PMID- 20799443
TI  - Round table discussion: potency--appropriate assays, hypoallergenic products.

PMID- 20799444
TI  - Physicochemical characterization of allergens: quantity, identity, purity,
      aggregation and conformation.
AB  - Allergens and allergoids can be characterized by means of physicochemical
      methods, resulting in a description of the protein on different structural
      levels. Several techniques are available and their suitability depends on the
      composition of the particular sample. Current European legislation on allergen
      products demands characterization of final products in particular focusing on
      identity, degree of modification (for allergoids) and stability of the
      composition. Structural parameters of allergens may be used to investigate the
      stability of an allergen product. The challenge is to identify and optimize
      techniques that allow determination of protein structure in the context of a
      formulated pharmaceutical product. As the majority of the products currently
      marketed are formulated with aluminium hydroxide or aluminium phosphate as a
      depot, most of the methods and techniques used for protein characterization in
      solution are not applicable. An additional hurdle is that allergen products are
      based on natural extracts, comprising a mixture of proteins, both allergens and
      non-allergens, sometimes in the presence of other uncharacterized components from
      the raw material. This paper describes which methods are suitable for the
      different stages of allergen product manufacturing, and how these relate to the
      current regulatory requirements. Some of the techniques are demonstrated using a
      model allergen, cod parvalbumin, and a chemically modified form thereof. We
      conclude that a variety of methods is available for characterization of proteins
      in solution, and that a limited number of techniques appear to be suitable for
      modified allergens (allergoids). Adaptation of existing methods, e.g. mass
      spectroscopy and infrared spectroscopy may be helpful to obtain protein
      parameters of allergens in a formulated allergen product. By choosing a
      combination of techniques, including those additional to physicochemical
      approaches, relevant parameters of allergens in formulated allergen products can
      be assessed in order to achieve a well-characterized pharmaceutical product.

PMID- 20799445
TI  - Application of proteomics for the characterization of biological allergen
      extracts.

PMID- 20799446
TI  - Characterization of allergoids.
AB  - So far it has not been possible to measure the amount of major allergens in the
      complexes after chemical modification. Furthermore, the presence of minor
      allergens remained obscure, unless antibodies were successfully generated by
      animal immunization with allergoids and shown to be reactive with purified
      natural or recombinant allergens in immunological assays. Thus, we adapted and
      employed a set of physicochemical methods with the aim of elucidating the
      molecular size and allergen composition of allergoids. Using online-HPSEC light
      scattering and DLS, it was shown that two thirds of depigmented allergoid
      prepared from birch pollen extracts adopted a MW between 1000 and 2000 kDa. The
      question of reproducibility of the polymerization reaction was addressed by
      investigating four batches of P. pratense allergoid. Three out of the four
      batches contained 73 to 77% of polymerized molecules in the above-mentioned range
      of molecular sizes. One batch showed a significantly higher content of molecules
      with a MW exceeding 2 MDa. Analysis of allergen composition in B. alba allergoids
      revealed the presence of all relevant Bet v 1 isoforms and minor allergens except
      for Bet v 3 and Bet v 4, which was in good agreement with the allergens detected
      in the native extracts. It should be noted that Bet v 3 has not been detected at
      the protein level before. Similarly, good agreement in allergen composition
      between allergoid and native extract was also found for D. pteronyssinus.
      Presently, the European Directorate for Quality of Medicines and Healthcare
      (EDQM) is committed to the application of the 3R principles (i. e. replace,
      reduce, refine the use of animals) for the quality control of medicines wherever
      possible. This is reflected by the regular review of the monographs of the
      European Pharmacopoeia and the introduction of alternative tests. For instance,
      recently it was decided to replace the rabbit pyrogen test by an in vitro test.
      Furthermore, through the Biological Standardisation Programme the EDQM develops,
      validates, and establishes alternative test methods in the field of quality
      control of biologicals (personal communication with Karl-Heinz Buchheit, EDQM).
      Therefore, the approach presented here for the characterization of allergoids
      relying on physicochemical methods shall also serve the growing needs for
      alternative methods to animal testing.

PMID- 20799447
TI  - Antibody-based methods for standardization of allergoids and recombinant
      hypoallergens.

PMID- 20799448
TI  - Specific immunotherapy by different allergen applications: subcutaneous,
      sublingual, oral or rectal administration and lymph node injection.

PMID- 20799449
TI  - Primary and secondary endpoints in clinical trials.

PMID- 20799450
TI  - State-of-the-art allergoids: overview of clinical trials.

PMID- 20799451
TI  - Potential uses of NIR and IR spectroscopy in quality control of allergy vaccine
      production.
AB  - BACKGROUND: Compared to conventional methods, infrared spectroscopy offers many
      potential uses in quality control of vaccine production. A major advantage is
      that the technique is non-invasive and non-destructive. In this study several
      possible uses of infrared spectroscopy in the control of allergy vaccines were
      investigated. METHODS: Near infrared spectroscopy (NIR) was applied to determine
      the aluminium content in aluminium hydroxide formulations, the particle size of
      aluminium hydroxide, the protein adsorption level on aluminium adjuvant and the
      moisture content of lyophilized vaccines. Mid infrared spectroscopy (IR) was used
      to investigate protein structural changes during adsorption and release from
      aluminium hydroxide and the stability of the complex. RESULTS: Based on the
      calibration models of NIR in different applications, it was demonstrated that NIR
      had great advantages for application in vaccine production. IR also showed
      advantages on structural analysis of adsorbed proteins. DISCUSSION: Infrared
      spectroscopy as a physical, non-invasive, non-destructive method should receive
      more attention in vaccine research and production.

PMID- 20799452
TI  - SQ-standardised grass tablet sublingual immunotherapy: persistent clinical
      benefit and progressive immunological changes during three years treatment.

PMID- 20799453
TI  - Diagnostic reagents for type I allergy--what criteria should be applied to
      validation?

PMID- 20799454
TI  - Design of clinical trials with patch test allergens in The Netherlands.

PMID- 20799455
TI  - Allergen microarrays for component-resolved diagnosis.

PMID- 20799456
TI  - The importance of molecular allergens for in vitro testing: a critical evaluation
      of component-resolved diagnostics.

PMID- 20799457
TI  - Responsibilities and new challenges for EDQM and the OMCL Network.

PMID- 20799458
TI  - Introduction to CHMP structures and procedures.

PMID- 20799459
TI  - A global view of allergenic product potency.

PMID- 20799460
TI  - New regulatory documents and procedures. I: Guideline on clinical trials of SIT
      products, European Pharmacopoeia, and note for guidance on allergen products.

PMID- 20799461
TI  - Regulation, role and future of named patient products in Germany.

PMID- 20799462
TI  - Regulatory aspects of clinical trials in children.
AB  - Since introduction of the EU Paediatric Regulation in January 2007 the
      development and the life cycle of a drug in pre- and post-authorisation period
      has changed significantly. Pharmacovigilance science has traditionally been a
      discipline focussed on the post-marketing or post-authorisation period, with due
      attention directed towards pre-clinical safety data, clinical trials and adverse
      events. As the biological sciences have evolved, pharmacovigilance has slowly
      shifted toward earlier, proactive consideration of risks and potential benefits
      of drugs in the pre- and post-approval stages of drug development, leading to a
      maturing of drug safety risk management. The development of drugs for the
      paediatric population has changed the awareness that not only the safety issues
      need to be thoroughly investigated for a safe treatment of the children. In
      conjunction with the knowledge about efficacy, pharmacokinetic/pharmacodynamic
      and the age appropriate formulation for the concerned drug, the impact on the aim
      to apply safe medicines for children will steadily increase. Therefore, a
      proposal for a joint effort performing clinical research and appropriate drug
      development and clinical trials in children needs a strong support from a number
      of stakeholders like Clinical Trial Network, Paediatric Society, pharmaceutical
      industry and authorities.

PMID- 20799463
TI  - Patient-tailored recombinant allergen products--mission impossible?

PMID- 20799464
TI  - Regulation of allergenic products in the United States: the promise and problem
      of adjuvants in allergen immunotherapy.

PMID- 20799465
TI  - Regulation of allergen products in Japan.
AB  - In Japan, standardization of allergens for therapeutics and diagnosis is very
      limited. Only one allergen (Cryptomeria japonica) extract was standardized. The
      standardization of two kinds of allergens for therapeutics (Cedar pollen and
      Dermatophagoides allergens) is now progressing. As for food allergens, the
      Japanese Ministry of Health Labour and Welfare (MHLW) made a decision for
      mandatory labeling of foods containing allergenic ingredients in 2001. Egg, milk,
      wheat, buckwheat and peanut, and most recently shrimp and crab require mandatory
      labeling. Standardization of food allergens for allergenic ingredient measurement
      has been advanced.

PMID- 20799466
TI  - Cellular responses, serological changes, or both: what are they good for?

PMID- 20799467
TI  - Different immunotherapy applications--different mechanisms? SLIT versus SCIT-
      differences in the mode of action.

PMID- 20799468
TI  - Protein families: implications for allergen nomenclature, standardisation and
      specific immunotherapy.
AB  - Allergens are embedded into the protein universe as members of large families and
      superfamilies of related proteins which is a direct consequence of their shared
      evolution. The classification of allergens by protein families offers a valuable
      frame of reference that allows the design of experiments to study cross
      reactivity and allergenic potency of proteins. Information on protein family
      membership also complements the current official IUIS allergen nomenclature. All
      presently known allergens belong to one of 140 (1.4%) of the 10,340 protein
      families currently described by version 23.0 of the Pfam database. This is
      indicative of a strong bias among allergens towards certain protein architectures
      that are able to induce an IgE response in an atopic immune system. However, even
      small variations in the structure of a protein alter its immunological
      characteristics. Various isoforms of the major birch pollen allergen Bet v 1 were
      shown to possess highly variant immunogenic and allergenic properties. Ber e 1
      and SFA8, two 2S albumins, were revealed to display differential capacities to
      polarise an immune response. Such data will be exploited in the future for the
      design of allergy vaccines.

PMID- 20799469
TI  - Clinical trials with recombinant allergens: research studies?

PMID- 20799470
TI  - Clinical trials with recombinant allergens--a regulatory perspective.

PMID- 20799471
TI  - Clinical trials with recombinant allergens--three perspectives: industry.

PMID- 20799473
TI  - Compliance and convenience to immunotherapy.

PMID- 20799472
TI  - Prophylactic allergen vaccination: current and future perspectives.
AB  - Allergen specific immunotherapy has traditionally been viewed as a treatment for
      established atopic disease. The disease target of choice has principally been
      allergic rhinitis, and in contrast there has been widespread reluctance in
      sectors of the clinical community to extend this approach to treatment of atopic
      asthma. However as understanding of the underlying pathogenic mechanisms which
      drive asthma aetiology and pathogenesis increases, the rationales for considering
      immunotherapy in this treatment context are expanding, particularly in relation
      to primary and secondary prevention of asthma in childhood. This brief review
      highlights recent development relating to this issue.

PMID- 20799474
TI  - Toll-like receptors as targets for enhancing the efficacy of immunotherapy.

PMID- 20799475
TI  - Treatment with a combination of anti-IgE and specific immunotherapy for allergic
      rhinitis and asthma.
AB  - Novel therapies that interfere specifically with immunological mechanisms
      underlying allergen-induced pathology are currently in clinical evaluation. Among
      these is anti-IgE, which directly targets IgE serum antibodies, thus inhibiting
      the central mechanism of immediate type hypersensitivity reactions. Application
      of anti-IgE antibodies effectively reduces IgE serum levels regardless of
      allergen specificity. It has been successfully tested in patients with allergic
      rhinitis, asthma and food allergy, showing significant efficacy in reducing
      symptom scores and use of rescue medications. Anti-IgE therapy is limited by high
      costs and the requirements for permanent or every-season treatment. The advantage
      of specific immune therapy (SIT) is the potential to alter the course of the
      disease, which has been demonstrated in patients with allergic rhinitis, insect
      venom allergy and, to a lesser degree, with asthma. The broader application of
      SIT is restricted by sometimes life-threatening side-effects. Here, we summarize
      the results of clinical trials investigating the effects of combination therapy
      with anti-IgE and SIT in patients with rhinitis and asthma. These studies show
      that combination of anti-IgE plus SIT may be beneficial for the treatment of
      allergic diseases by improving efficacy and limiting side effects.

PMID- 20799476
TI  - IVN201--therapy with a construct containing functional fusion peptides.
AB  - The new concept of immunotherapy with IVN201 against cat dander allergy combines
      two proprietary technology platforms: Intralymphatic immunotherapy (ILIT) with
      Modular-Antigen-Transportation (MAT) proteins. Intralymphatic immunotherapy
      (ILIT) is the injection of immunotherapeutics directly into the lymph node. Lymph
      nodes contain a high density of antigen presenting cells together with
      interacting T cells, which are necessary for allergen tolerance development.
      Therefore, this site-directed route of administration requires fewer injections
      of much smaller doses of the allergen than conventional administration routes to
      induce a highly effective, disease modifying immune response. ILIT was recently
      demonstrated in a clinical study to enhance safety and efficacy of immunotherapy
      and to reduce treatment time from 3 years to 8 weeks with only three injections,
      thereby significantly improving patient compliance. Patients subjectively
      perceived the intralymphatic injections less painful than a venous puncture.
      IVN201 is a functional fusion peptide which is a tailor-made recombinant allergen
      for ILIT with Fel d 1 as allergen module. It is designed to be rapidly taken up
      by antigen presenting cells in the lymph nodes and to improve the presentation of
      the allergen to the immune system. IVN201 was shown to induce allergen tolerance
      in a murine anaphylaxis model. Stimulation assays with basophil leukocytes
      isolated from allergic patients suggest an increased safety profile when compared
      to cat extract or recombinant Fel d 1. Therefore, MAT molecules are expected to
      be safer and more efficacious in inducing the desired immune response than
      recombinant allergens or allergen extracts in allergen immunotherapy when
      administered via the intralymphatic route.

PMID- 20799477
TI  - Sublingual immunotherapy for food allergy.

PMID- 20799478
TI  - A novel multi-potential dendritic cell targeted gene vaccination platform;
      application to food allergy and beyond.

PMID- 20799479
TI  - Allergy vaccination with peptides--SIT with major cat allergen Fel d 1 peptides:
      safety, tolerability and dose responses.

PMID- 20799480
TI  - [The National Organization of Nurses will negotiate but does not yield].

PMID- 20799481
TI  - [Regional health agencies want to combine proximity, efficiency and cooperation].

PMID- 20799482
TI  - [Cultural dimensions in nursing situations. Cultural competence will make all the
      difference].

PMID- 20799484
TI  - [Healthcare and culture, between diversity and universality].
AB  - Interrelations exist between people's behaviour and the reasons for it as
      explained by culture. The healthcare theory put forward by the American nurse
      Madeleine Leininger, at the end of the 1970s, integrates anthropology Identifying
      and understanding the patient's culture enables nursing care to be adapted to the
      patient's own view of his/her disease.

PMID- 20799483
TI  - [Culture and nursing care, from a biomedical to an anthropological approach].
AB  - Nursing training and practice have for a long time taken a biomedical approach to
      disease and the body, which fails to guarantee treatment which takes into account
      the differences of each patient. With transcultural healthcare theories and
      practices, partly inspired by anthropology, patients are explicitly considered as
      subjects whose experiences are a result of cultural, ethnic and social
      dimensions.

PMID- 20799485
TI  - [Cultural competence in the healthcare relationship with migrant patients].
AB  - The nursing encounter in an intercultural context focuses on culture as a central
      element of the healthcare relationship. Learning cultural competence enables
      nurses to understand others without stigmatizing them.

PMID- 20799486
TI  - [Hospitalization, new unknown territory for migrants].
AB  - Hospitalisation upsets the patient's life course, with individual psychosocial
      consequences the intensity of which varies according to the background of each
      patient. Some factors, such as the migration experience, impact the adjustment of
      foreign patients to hospitalisation.

PMID- 20799487
TI  - [The health education nurse faced with an African HIV-infected patient].
AB  - The health education nurse faced with an African HIV-infected patient. Disease
      and death are represented in a completely different manner in Sub-Saharan Africa
      than in the West. The role of the health education nurse working with African HIV
      infected patients requires a socio-ethnological understanding of this cultural
      context in order to provide a global, personalised and adapted treatment.

PMID- 20799488
TI  - [Avoiding the stereotypes of the culturalist approach in healthcare].
AB  - Healthcare institutions often turn to training organisations to train healthcare
      workers in an intercultural healthcare approach. The culturalist approach,
      usually expected from such training, is not always the most suitable. Working on
      differences provides a better understanding of the representations of patients
      and helps to avoid prejudices.

PMID- 20799489
TI  - [Healthcare for African patients provided by NGOs].
AB  - The humanitarian organisation Medecins d'Afrique works to promote access to
      healthcare for African patients, in France and in Africa. Through intercultural
      partnerships and training for healthcare professionals, it contributes to health
      promotion.

PMID- 20799490
TI  - [Impact of the institutional framework and context of intercultural nurse
      relations: nurses].

PMID- 20799491
TI  - [Elements of bibliography].

PMID- 20799492
TI  - [6/10. Writing about clinical reasoning (2/)].

PMID- 20799494
TI  - Hospitals must reduce readmissions as CMS moves to cut reimbursement.

PMID- 20799493
TI  - [5/5. Parkinson disease].

PMID- 20799495
TI  - Project to reduce costs for Medicare beneficiaries.

PMID- 20799496
TI  - Medical home model helps DP process with care.

PMID- 20799497
TI  - CMS adds outpatient data to website.

PMID- 20799499
TI  - Is 'boarded' care viewed as substandard?

PMID- 20799498
TI  - Collaboration on capacity management.

PMID- 20799500
TI  - MedPAC: PAC-MAN for the new millennium?

PMID- 20799501
TI  - Zoom in, zoom out: keeping Boomers in motion. Helping Baby Boomers reap the joy
      of movement/avoid pitfalls of exercise injury.

PMID- 20799502
TI  - Water works. Baby Boomers drive trend toward state-of-the-art aquatic therapy.

PMID- 20799503
TI  - Getting back in the game. Rehabbing lower extremity injuries and helping to stave
      off recurrence.

PMID- 20799504
TI  - Q-and-A: The perfect fit. How documentation systems have helped streamline
      operations for PTs, OTs, and SLPs at Tallahassee Memorial Rehabilitation Center
      in Florida. Interview by Judy O'Rourke.

PMID- 20799505
TI  - LTACH 2011 proposed rules and the initial impact of health care reform.

PMID- 20799506
TI  - Cancer in Puerto Rico: disease burden, public policy, research and training.

PMID- 20799507
TI  - Vitamin C and cancer: what can we conclude--1,609 patients and 33 years later?
AB  - In 1976 an article co-authored by Linus Pauling described that 100 terminal
      cancer patients treated with intravenous vitamin C, followed by oral maintenance,
      lived four times longer than a control group of 1,000 patients who did not
      receive vitamin C. The study was strongly criticized because the control group
      was very different from the group treated with vitamin C. The latter were
      declared terminally ill much sooner than the control group thus resulting in an
      artificially longer survival for the vitamin C group. Three double blind placebo
      controlled randomized trials performed at Mayo Clinic using oral vitamin C for
      cancer patients were negative. In a phase I-II trial performed by Riordan et al,
      none of 24 cancer patients treated with i.v. vitamin C responded. At this point
      we don't have information as to which is the actual plasma level of vitamin C
      that can produce tumor shrinkage. We don't have consistent information either
      regarding what is the clinical dose necessary to yield therapeutic plasma levels.
      In view of this lack of data after trials which have included at least 1,591
      patients over 33 years, we have to conclude that we still do not know whether
      Vitamin C has any clinically significant antitumor activity. Nor do we know which
      histological types of cancers, if any, are susceptible to this agent. Finally, we
      don't know what the recommended dose of Vitamin C is, if there is indeed such a
      dose, that can produce an anti-tumor response.

PMID- 20799508
TI  - Regulations and recommendations for appropriate disposal of antineoplastics.

PMID- 20799511
TI  - Productivity loss in Puerto Rico's labor market due to cancer mortality.
AB  - BACKGROUND: In Puerto Rico (PR), cancer is the second leading cause of death and
      the disease that causes most premature deaths, representing about 15% of them.
      Thus, premature death due to cancer decreases the productivity capacity in PR.
      OBJECTIVE: This study aimed to estimate the labor-market productivity loss in PR
      during 2004 as a result of premature mortality due to overall cancer and cause
      specific cancers. METHODS: A model based in the incidence-based approach and in
      the human capital approach was developed to estimate the labor-market
      productivity loss. Economic data were obtained from the Public Use Microdata
      Sample (PUMS) of the PR Community Survey (PRCS). Mortality data were obtained
      from the Vital Statistics of the PR Department of Health. RESULTS: The
      productivity costs of all cancer deaths were estimated to be approximately $64
      million (in constant value). The cancer deaths that contributed the most to
      productivity loss were lung and bronchus, colorectal, breast, and liver and
      intrahepatic bile duct. CONCLUSIONS: Although these results must be interpreted
      with caution, this study contributes to show a broader picture that includes the
      economic dimension of cancer in our society. These estimates imply that
      productivity cost due to cancer mortality have a great burden in PR. The leading
      cancer sites that generate most productivity losses are highly preventable or can
      be diagnosed early or are related to tobacco consumption. This study should be
      considered within the framework of future cost analyses for the development of
      health and cancer control policies.

PMID- 20799509
TI  - Current and future applications of magnetic resonance imaging (MRI) to breast and
      ovarian cancer patient management.
AB  - Magnetic resonance imaging (MRI) is occupying an increasing niche in the clinical
      diagnostic workup of several cancers, including breast cancers. Despite the high
      level of implementation of mammography, it has become apparent that MRI can play
      at least a complementary role in the imaging and diagnosis of primary breast
      cancers, including ductal carcinoma in situ, the earliest stage of breast cancer
      that is associated with an increased risk of invasive breast cancer. This can
      also be said of inflammatory breast cancer, of low incidence but with high impact
      on overall breast cancer mortality rates, and for which mammography is not ideal
      due to the typically diffused nature of this disease. Much of the value of breast
      MRI is dependent on its high sensitivity, resulting from the use of contrast
      agent enhancement in the detection of breast cancer. Interest has also increased
      in the application of diffusion-weighted MRI for early assessment of treatment
      response in this disease. Regarding ovarian and other gynecological cancers, MRI
      has already demonstrated value in the evaluation of patients with ovarian masses,
      uterine leiomyoma, endometrioma, and cervical cancer. Features on MRI suggestive
      of malignant ovarian tumors are varied, and span irregular or solid components to
      a cystic mass, prominent septations, evidence of peritoneal, hematogenous, or
      lymphatic spread, or local invasion. The majority of ovarian malignancies are
      diagnosed in advanced, incurable stages, where exploratory laparotomy provides
      the opportunity for maximal debulking. Although a role for MRI has yet to be
      established in this initial setting or in staging, some studies have shown that
      high sensitivity may be achieved with contrast agent-enhanced MRI for detection
      of recurrent disease, including demonstration of macroscopic intraabdominal
      dissemination and the hallmark omental "cake". Efforts in recent years have been
      focused on design of MRI contrast agents (MRI-CAs), which either target
      biomarkers, or take advantage of the different physiology of cancerous cells. MRI
      CAs based on gadolinium complexes, ferrumoxides, or other metallic nanoparticles
      have been investigated. This review will focus on the recent progress in the
      application of MRI to the imaging of breast and ovarian cancers, and present a
      possible role for molecularly-targeted contrast agents in enriching the context
      for MRI-based diagnosis.

PMID- 20799510
TI  - Burden of human papillomavirus infection and related comorbidities in men:
      implications for research, disease prevention and health promotion among Hispanic
      men.
AB  - Genital human papillomavirus (HPV) infection is one of the most commonly
      diagnosed sexually transmitted infections world-wide. Over the last two decades,
      research has established a strong causal link between specific types of HPV
      infection and cancer, particularly cervical, anal, vulvar/vaginal, penile, and
      oropharyngeal cancer. Limited epidemiological studies of anogenital HPV infection
      have been conducted in Hispanic populations (including Puerto Rico), and
      population-based incidence and prevalence estimates of HPV infection among
      Hispanics are limited. Studies that evaluate knowledge and awareness of HPV among
      men are also scarce. With the world-wide introduction of two new prophylactic
      vaccines against high-risk HPVs causing cervical cancer, and the recent FDA
      approval of the quadrivalent vaccine in preventing genital warts in men, there is
      an urgency to determine the burden of HPV in Hispanic populations before vaccine
      programs are implemented on a widespread basis. Knowledge and acceptability of
      the vaccine prior to implementation of these programs are also necessary to allow
      a targeted assessment. This review article summarizes existing research on HPV
      infection and HPV-related morbidities in men, with a particular emphasis on
      Hispanic men in the United States and Puerto Rico. Three major areas are
      discussed: (1) genital warts, (2) HPV and related cancers and (3) biobehavioral
      and psychosocial factors related to HPV infection and vaccination. Specific
      recommendations for advancing HPV research and knowledge among Hispanic
      populations also are suggested.

PMID- 20799512
TI  - Assessing the scientific research productivity of Puerto Rican cancer
      researchers: bibliometric analysis from the Science Citation Index.
AB  - OBJECTIVE: The analysis of cancer scientific production in Puerto Rico is largely
      unexplored. The objective of this study was to characterize trends in cancer
      related research publications by authors affiliated to Puerto Rican institutions
      in recent decades. METHODS: Manuscripts were retrieved from the Science Citation
      Index (SCI) database from 1982 to 2009. Search criterions were that the author's
      affiliation field contained some institution located in Puerto Rico and that the
      manuscripts were related to cancer research (according to keywords from the
      National Cancer Institute' cancer definition). Indexes measured in our analysis
      included number and type of manuscript, scientific collaboration, author's
      affiliation, and journal visibility. All the analyses were conducted using
      ProCite for bibliographic information management and STATA and SEER Joinpoint for
      the statistical inquiry. RESULTS: From 1982-2009, cancer-related papers authored
      by scientists located in Puerto Rico came to 451. Over the last three decades the
      scientific production underwent significant growth (APC = 6.4%, p < 0.05) with
      the highest peak between 2000 and 2009 (61.4% of all articles). Universities are
      the local institutional sector with the highest number of authors (81.4%), and
      the University of Puerto Rico is the most active center in this regard (68.5%).
      Forty-three percent of the manuscripts (n = 195) were published in 20 journals
      from which 14 are observed to have high visibility when compared to similar
      thematic journals. CONCLUSIONS: Cancer-scientific production in Puerto Rico
      underwent constant growth during the last three decades. A complete understanding
      of citing, publishing, and collaboration patterns in Puerto Rico is critical to
      researchers, policy makers, and health-care professionals in order to make
      informed decisions about cancer research priorities.

PMID- 20799513
TI  - Risk of cancer among Hispanics with AIDS compared with the general population in
      Puerto Rico: 1987-2003.
AB  - BACKGROUND: The risk of cancer among Hispanics with Acquired Immune Deficiency
      Syndrome (AIDS) in the United States and Puerto Rico (PR) has not been well
      described. The purpose of this study was to determine the risk of AIDS related
      and non-AIDS related cancers among Hispanics with AIDS in PR. METHODS: A
      probabilistic record linkage of the PR AIDS Surveillance Program and PR Central
      Cancer Registry databases was conducted. AIDS cases were grouped according to
      year of AIDS onset and antiretroviral therapy availability: 1987-1989 (limited
      availability), 1990-1995 (mono and dual therapy), and 1996-2003 (highly active
      antiretroviral therapy: HAART). Cancer risk was described using the standardized
      incidence ratios (SIR). RESULTS: A total of 612 cancers were identified after 3
      months of AIDS diagnosis: 409 (66.7%) AIDS related and 203 (33.1%) non-AIDS
      related. Although a decreasing trend in the risk of AIDS and non-AIDS related
      cancers was observed, the risk for both remained higher in the AIDS group
      compared to the general population in PR. Non-AIDS related cancers with higher
      risk during the HAART availability were: oropharyngeal, anal, liver, larynx, eye
      and orbit, Hodgkin lymphoma, and vaginal. CONCLUSION: Hispanics with AIDS in PR
      consistently showed a greater risk of AIDS and non-AIDS related cancers compared
      to the general population in PR and that has not changed over time.

PMID- 20799514
TI  - Clinicopathological factors associated to HER-2 status in a hospital-based sample
      of breast cancer patients in Puerto Rico.
AB  - Breast cancer is the most common female malignancy in Puerto Rico. Cases with
      human epidermal growth factor receptor 2 (HER-2) oncoprotein overamplification
      are associated with aggressive clinical behavior. Given the limited availability
      of information for Puerto Rico, we aimed to evaluate the prevalence and clinical
      correlates of HER-2 gene overexpression among a hospital-based female population
      of breast cancer cases. We analyzed data from 1,049 female patients with invasive
      breast cancer (diagnosed 2000-2005) at the I. Gonzalez Martinez Oncologic
      Hospital and the Auxilio Mutuo Hospital. HER-2 status and other clinical
      characteristics were retrieved from the hospitals' cancer registries, from the
      Puerto Rico Central Cancer Registry, and from a review of medical and
      pathological records. Prevalence odds ratios were estimated with 95% confidence
      intervals, using logistic regression models to quantify the association between
      HER-2 status and different clinicophatological factors. The overall prevalence of
      positive HER-2 expression was 22.5%. In the multivariate logistic regression
      model, factors significantly associated with HER-2 positivity included a
      diagnosis age of < 50 years, having a tumor with negative progesterone receptor
      (PR) status, and having regional disease (p < 0.05). No significant differences
      in HER-2 positivity were observed by tumor histology or estrogen receptor (ER)
      status (p > 0.05). This is the most comprehensive epidemiological study to date
      on HER-2 status in Puerto Rico. The prevalence and correlates of HER-2
      overexpression in this study are comparable to those observed in US populations.
      Study results will aid in the development of breast cancer control strategies in
      Puerto Rico.

PMID- 20799515
TI  - Clinic-based case-control study of the association between body mass index and
      endometrial cancer in Puerto Rican women.
AB  - BACKGROUND: Obesity is an established risk factor for endometrial cancer (EC).
      This association, however, has not been studied in Puerto Rico, where overweight
      and obesity have reached epidemic levels (38% and 26%, respectively). METHODS: A
      hospital based case-control study was designed to evaluate the association
      between body mass index (BMI) and EC in women older than 21 years of age. Seventy
      four prevalent EC cases diagnosed between January 2004 and August 2007 and a
      random sample of 88 healthy controls were recruited from gynecology clinics of
      the Medical Sciences Campus, University of Puerto Rico. Demographic,
      reproductive, lifestyle, and clinical information was obtained via structured
      telephone interviews and medical chart review. Unconditional logistic regression
      models were used to estimate adjusted odds ratios (OR) and 95% confidence
      intervals (CI). RESULTS: A significant trend was observed between BMI and EC in
      bivariate analyses (p < 0.05). Results showed that overweight (25.0 > BMI < 29.9
      kg/m2) (OR = 4.4, 95% CI = 1.6-12.3) and obese (BMI < or = 30 kg/m2) (OR = 9.9,
      95% CI = 3.6-26.9) women were more likely to have EC when compared to non-obese
      women. In multivariate analysis, obese women had a 4-fold greater possibility of
      EC (OR = 4.1; 95% CI: 1.8-8.6) than nonobese women, after adjusting for age,
      education, employment status, hypertension and diabetes diagnosis, use of oral
      contraceptives and consumption of poultry. CONCLUSION: Consistent with previous
      studies worldwide, adult obesity was a strong predictor for EC in this sample of
      Puerto Rican women. Thus, cancer control strategies should promote weight
      reduction strategies to reduce disease risk in this population.

PMID- 20799516
TI  - The effect of the smoke-free workplace policy in the exposure to secondhand smoke
      in restaurants, pubs, and discos in San Juan, Puerto Rico.
AB  - BACKGROUND: Tobacco use and the involuntary exposition to secondhand smoke (SHS)
      is one of the leading causes of all cancers in the world. The objective of this
      study was to assess the effect of the smoke-free workplace policy implemented in
      March of 2007 in Puerto Rico on the exposition to secondhand smoke in
      restaurants, pubs, and discos of the metropolitan area of San Juan, Puerto Rico.
      METHODS: The study used a pre-post comparison design on a random sample of 55
      establishments (32 restaurants and 23 pubs and discos) in the metropolitan area
      of San Juan, Puerto Rico. Measurements of indoor concentrations of fine
      particulate matter (PM) (2.5 mm diameter, PM2.5) were taken before and after the
      introduction of the law banning smoking using a SidePak AM510 Personal Aerosol
      Monitor (TSI Company). Also, data on the number of smokers, number of customers,
      and establishment area was collected. Paired t-tests and linear regression
      analyses were used to test any statistically significant effect of the law.
      RESULTS: After the smoking ban was implemented, restaurants experienced an 83.6%
      (p = 0.013) reduction in the mean of PM 2.5 levels, from 0.169 to 0.028 mg/ m3,
      and pubs and discos experienced a 95.6% (p = 0.004) reduction, from 0.626 to .028
      mg/m3. CONCLUSION: The implementation of the smoke-free workplace policy
      considerably reduced the exposition to SHS of workers and customers in the
      restaurants, pubs, and discos of the metropolitan area of San Juan, Puerto Rico.

PMID- 20799517
TI  - Stereotactic radiosurgery for intracranial tumors: Puerto Rico experience.
AB  - Historically, the treatment for most intracranial pathologies has included
      medical management, surgery, radiotherapy and recently, stereotactic
      radiosurgery. Since its introduction, stereotactic radiosurgery has evolved from
      an investigational concept into a recognized neurosurgical procedure for the
      management of a wide variety of brain disorders. The goal of this research was to
      describe the experience in Puerto Rico using this technology and review the
      efficacy, safety, and role of radiosurgery in the treatment of the most common
      intracranial tumors treated today. Patients treated from 1999-2009 at Clinicas
      Las Americas were reviewed and medical literature databases were searched for
      articles pertaining to stereotactic radiosurgery performed in these intracranial
      tumor pathologies: meningiomas, gliomas, cerebral metastasis, vestibular
      schwannomas and pituitary adenomas. Each study was examined to determine the
      radiosurgical parameters, duration of follow-up review, tumor growth control rate
      and complications. A total of 50 peer-reviewed studies were examined.
      Radiosurgery in benign tumors resulted in the control of tumor size in 90% of
      treated patients. Unfortunately radiosurgery for malignant tumors is not
      curative, but has been effective in improving survival and quality of life.
      Although microsurgery remains the primary treatment modality in most cases,
      stereotactic radiosurgery offers both safe and effective treatment for much
      intracranial pathologies. Further refinements in the radiosurgical technique will
      likely lead to improved outcomes and make it a standard of care.

PMID- 20799518
TI  - Modeling a radiotherapy clinical procedure: total body irradiation.
AB  - Leukemia, non-Hodgkin's lymphoma, and neuroblastoma patients prior to bone marrow
      transplants may be subject to a clinical radiotherapy procedure called total body
      irradiation (TBI). To mimic a TBI procedure, we modified the Jones model of bone
      marrow radiation cell kinetics by adding mutant and cancerous cell compartments.
      The modified Jones model is mathematically described by a set of n + 4
      differential equations, where n is the number of mutations before a normal cell
      becomes a cancerous cell. Assuming a standard TBI radiotherapy treatment with a
      total dose of 1320 cGy fractionated over four days, two cases were considered. In
      the first, repopulation and sub-lethal repair in the different cell populations
      were not taken into account (model I). In this case, the proposed modified Jones
      model could be solved in a closed form. In the second, repopulation and sub
      lethal repair were considered, and thus, we found that the modified Jones model
      could only be solved numerically (model II). After a numerical and graphical
      analysis, we concluded that the expected results of TBI treatment can be mimicked
      using model I. Model II can also be used, provided the cancer repopulation factor
      is less than the normal cell repopulation factor. However, model I has fewer free
      parameters compared to model II. In either case, our results are in agreement
      that the standard dose fractionated over four days, with two irradiations each
      day, provides the needed conditioning treatment prior to bone marrow transplant.
      Partial support for this research was supplied by the NIH-RISE program, the LSAMP
      Puerto Rico program, and the University of Puerto Rico-Humacao.

PMID- 20799519
TI  - Genetic variants of the drug-metabolizing enzyme CYP2D6 in Puerto Rican
      psychiatry patients: a preliminary report and potential implications for breast
      cancer patients.
AB  - BACKGROUND: The CYP2D6 liver enzyme, which metabolizes 25-30% of common
      medications, is highly polymorphic. Existing studies of Hispanics have focused on
      Mexicans and Mexican-Americans. The goal of the study was to identify the CYP2D6
      alleles associated with reduced or negligible activities present in the Puerto
      Rican population. METHODS: The study cohort comprised 40 Puerto Rican psychiatric
      patients referred because of suspected intolerance of drugs metabolized by
      CYP2D6, and five subjects without suspected adverse responses to these drugs. All
      subjects had both parents and all grandparents born in Puerto Rico. Genomic DNA
      was queried for 27 CYP2D6 alleles using the Roche AmpliChip P450 test. RESULTS: A
      total of 12 alleles were identified. The most common alleles were CYP2D6*1 > *2 >
      *4 > *41. The inactive alleles were *4 > * 5 > * 31 >*40; reduced activity
      alleles were *10 >* 17 > *9* = *29; active alleles were *1 > *2 > *35. Two
      subjects carried the rare *31 allele. Only one subject carried two non-functional
      alleles (CYP2D6*5/*40), and was predicted to be a poor metabolizer. CONCLUSIONS:
      Any conclusions should be interpreted with caution given the small population
      sample investigated. Nonetheless, our findings strongly suggest that Puerto
      Ricans exhibit distinct CYP2D6 allele frequencies and harbor a non-functional
      allele that is rare or absent in other populations and are highly valuable for
      the emerging practice of Personalized Medicine in admixed populations like Puerto
      Ricans.

PMID- 20799520
TI  - Two novel nonparametric methods for cancer diagnosis through microarray analysis.
AB  - Diagnosing cancer using microarray analysis to study differential gene expression
      has been a recent focus of intense research Although several very sophisticated
      analysis tools have been developed with this aim in mind, it still remains a
      challenge to keep these methods free of parametric adjustments as well as
      maintain their transparency for the final user. Nonparametric methods in general
      have been associated with these last two characteristics, thus becoming
      attractive tools for microarray analysis in cancer research. In particular,
      diagnosing cancer via microarray analysis is an exercise whereby tissue is
      characterized according to its differential gene expression levels. In this
      manuscript, two novel nonparametric methods for cancer diagnosis using microarray
      data are described and their performance assessed against a baseline approach
      that utilizes the Mann-Whitney test for median differences. Both methods show
      promising results in terms of their potential use in making diagnoses.

PMID- 20799521
TI  - Skin cancer in Puerto Rico: a multiannual incidence comparative study.
AB  - BACKGROUND: The incidence of skin cancer continues to increase worldwide. The
      purpose of this study was to determine the incidence of skin cancer in Puerto
      Rico in a selected year (2005) and to compare these findings with those
      previously reported for Puerto Rico in 1974 and 1981 and with other countries.
      METHODS: The data was collected from the pathology reports corresponding to the
      period of January to December 2005 of 21 participating Pathology Laboratories
      throughout Puerto Rico. The rate and distribution of the main types of skin
      cancer was calculated based on sex, age, anatomic location and laterality.
      RESULTS: The incidence of skin cancer in Puerto Rico for 2005 was 6,568 cases,
      which represent a rate of 167.9 per 100,000 inhabitants. The most common type of
      skin cancer was basal-cell carcinoma. Skin cancer was more common in males except
      for melanoma, which was more common in females. The incidence increases with age
      on all types of skin cancer. The head and neck area was the most frequent
      location, except for melanoma in women, which was more common on the legs. The
      incidence rate was 41.5/100,000 in 1974, 52.5/100,000 in 1981 and 167.9/100,000
      in 2005, a 305% increase. CONCLUSIONS: We found an increasing incidence of skin
      cancer in Puerto Rico when compared with previous reported data. This analysis
      provides a comprehensive evaluation of the epidemiology of skin cancer in Puerto
      Rico.

PMID- 20799522
TI  - Incidence and mortality of the leading cancer types in Puerto Rico: 1987-2004.
AB  - BACKGROUND: Cancer remains one of the leading causes of morbidity and mortality
      worldwide and is the second cause of death in Puerto Rico (PR). This article
      describes the incidence and the mortality from cancer in PR for the period of
      1987 to 2004. METHODS: We analyzed data from the PR Central Cancer Registry and
      the PR Demographic Registry from 1987-2004, for the leading cancer types in men
      and women in PR. Age-adjusted incidence and mortality rates were estimated by
      sex, municipality, health region and primary site and were age-standardized to
      the 2000 PR population. RESULTS: Incidence rates for overall cancer remained
      constant in men and increased in women (APC = 0.6%, p < 0.05), while mortality
      rates decreased (APC = -1.0%) for both sexes. A significant increase was observed
      in the cancer incidence rates for colorectal cancer in men, while in women, an
      increase in breast, colorectal, and corpus and uterus cancer was observed.
      Mortality rates decreased for most of the major cancers types in both sexes,
      except for colorectal cancer in men which showed a significant increase (p <
      0.05). CONCLUSION: The most important cancer types in PR (prostate, breast,
      colorectal, and lung) for both incidence and mortality are susceptible to primary
      prevention (eliminating or reducing risk factors) or to secondary prevention
      (early diagnosis) strategies. Our results are essential for the development of
      cancer prevention and control strategies in the Island.

PMID- 20799524
TI  - Cancer research training in Puerto Rico: challenges and opportunities.

PMID- 20799523
TI  - Cutaneous adrenal cortical carcinoma metastasis in a 6 year-old boy.
AB  - We report the case of a six year-old boy with a history of adrenal cortical
      carcinoma presenting with cutaneous metastasis. Due to the low incidence of
      cutaneous metastasis arising from adrenal cortical carcinoma, its diagnosis can
      be challenging based solely on histological analysis. Yet, the clinical history
      in combination with an immunohistochemical panel consisting of melan-A, alpha
      inhibin, D11, caretinin, neuron specific enolase, synatophysin, and chromogranin,
      can be useful in differentiating it from other tumors with similar
      cytomorphology.

PMID- 20799525
TI  - The 21st century, 5 of the 10 leading causes of death were related to chronic and
      noncommunicable diseases.

PMID- 20799526
TI  - International study of asthma and allergies in childhood: phase 3 in the Syrian
      Arab Republic.
AB  - The International Study of Asthma and Allergies in Childhood (ISAAC) uses
      standardized symptom-based questionnaires to describe the prevalence of symptoms
      of asthma, rhinoconjunctivitis and eczema in children worldwide. Three
      governorates in the Syrian Arab Republic (Aleppo, Lattakia and Tartous)
      participated in ISAAC phase 3 in 2001-03. Adolescents in the 13-14 year age group
      and parents of the 6-7-year-old children completed the questionnaire about asthma
      symptoms. The prevalence of current symptoms of asthma (wheezing in the last 12
      months) in different centres ranged from 4.7% to 5.7% for 6-7-year-olds and 3.9%
      to 6.5% for 13-14-year-olds. In 13-14-year-olds the prevalence of severe speech
      limiting wheeze was 2.0%-3.5%, of rhinoconjunctivitis was 8.6%-14.6% and of
      eczema was 3.3%-4.2%.

PMID- 20799527
TI  - Household characteristics and allergen and endotoxin levels in Aleppo, Syrian
      Arab Republic.
AB  - Few data are available from Eastern Mediterranean countries about levels of
      domestic allergens and endotoxins. Dust samples were collected from mattresses
      and floors of 457 homes in the Syrian city of Aleppo and analysed for antigens
      and endotoxins. The most important predictors for detectable levels of house-dust
      mite allergen Der p 1 were Arabic-style houses (OR 3.21) and newer houses (OR
      1.56). In homes without cats, rubber mattresses were associated with detectable
      cat allergen Fel d 1 in mattress dust (OR 1.6). Cockroach allergen Bla g 2 was
      significantly more likely to be detected in houses over 20 years old than newer
      houses. Endotoxin levels were significantly higher in wool/cotton mattresses and
      older houses.

PMID- 20799528
TI  - Screening for diabetes in Kuwait and evaluation of risk scores.
AB  - This study aimed to develop a simple risk score to identify individuals at high
      risk for undiagnosed diabetes in the Kuwaiti adult population and to assess the
      performance of previously published diabetes risk scores. A cross-sectional
      survey with a sample of 562 Kuwaiti public sector employees was carried out in
      2007. Data were collected through a self-administered questionnaire and a blood
      glucose test. The overall prevalence of diabetes using American Diabetes
      Association 2003 criteria was 21.4% (4.1% newly detected). The proposed score had
      87% sensitivity and 64% specificity in predicting undetected diabetes using only
      4 questions (age, waist circumference, use of blood pressure medication and
      diabetes in a sibling). Most previously published risk scores were not applicable
      to this population.

PMID- 20799529
TI  - Glycaemic control and its associated factors in type 2 diabetic patients in
      Amman, Jordan.
AB  - A study of 1000 patients attending a diabetes referral centre in Amman, Jordan,
      identified factors associated with good glycaemic control, as measured by
      glycosylated haemoglobin (HbA1c) levels. Glycaemic control improved significantly
      between the first clinic visit and at 12-months follow-up. The proportion of
      patients with extreme HbA1c (> or = 10%) decreased from 15.3% to 6.0% after 12
      months. The percentage of patients with optimal control (HbA1c < 7%) increased
      from 25.4% at the first visit to 27.5% at 12-month follow-up. Multivariate
      regression showed that low body mass index, shorter duration of diabetes and
      higher baseline HbA1c were related to reductions in HbA1c between the first and
      12-month visits.

PMID- 20799530
TI  - Type A behaviour pattern: is it a risk factor for hypertension?
AB  - Type A behaviour pattern has been found to be associated with coronary heart
      diseases, but its association with hypertension is inconsistent. To investigate
      the association between type A behaviour pattern and hypertension, 221 known
      hypertensive patients and a control group of 221 non-hypertensive patients in
      Basra, Iraq, were interviewed for type A behaviour using to a special
      questionnaire. Blood pressure, height and weight were measured. The proportion
      with type A behaviour was significantly higher in hypertensive than non
      hypertensive patients (57.5% versus 24.9%) and a highly significant association
      was found between type A behaviour and hypertension (OR 4.08, 95% CI: 2.72-6.11).
      Type A behaviour pattern was shown to be an independent risk factor for the
      development of hypertension.

PMID- 20799531
TI  - [Prevalence of overweight and obesity in schoolchildren in Tebessa (Algeria)
      between 1998 and 2005].
AB  - We studied the prevalence of obesity and overweight in schoolchildren aged 5-8
      years in Tebessa, Algeria between 1998 and 2005. All schoolchildren in 5 primary
      schools (n = 3396) were included. Age, sex, height and weight were recorded. For
      classification of obesity and overweight the International Obesity Task Force
      definitions was used. The prevalence of obesity and overweight for the total
      sample was 6.36% and fell from 7.44% in 1998 to 5.81% in 2005. The prevalence of
      obesity was higher in girls than boys (1.58% vs 1.26%) (P = 0.430) while the
      prevalence of overweight was higher in boys than girls (5.60% vs 4.18%) (P =
      0.057).

PMID- 20799532
TI  - Domestic abuse before, during and after pregnancy in Jahrom, Islamic Republic of
      Iran.
AB  - We conducted a cross-sectional study among 300 women with a child aged 6 to 18
      months, to determine the prevalence and determinants of domestic abuse against
      women in Jahrom; before, during and after pregnancy. The prevalence of abuse
      during pregnancy (42%) was lower than during the 1 year before pregnancy (51.7%)
      and after delivery (53.5%). The overall prevalence of emotional abuse, sexual
      abuse and physical abuse was 53.5%, 34.7% and 26.7% respectively. Abuse during
      any previous period was a strong risk factor for subsequent abuse. Other risk
      factors associated with abuse were: woman previously witnessing domestic
      violence, opium use by husband, woman's education < or = 12 years, age at
      marriage of woman < 18 years, husband's education < or = 12 years, woman's
      economic dependency and living in an extended family. Routine screening of abuse
      in maternity clinics should be considered.

PMID- 20799533
TI  - Determinants of maternal adaptation to mentally disabled children in El Minia,
      Egypt.
AB  - This study was carried out in a governmental school for mentally disabled
      children in El Minia. We assessed maternal adaptation and the relationship
      between maternal sociodemographic factors and adaptation as well as examining
      maternal distress. All 100 mothers with children aged 6-18 years attending the
      school were recruited in the study. Three tools were used: demographic data
      sheet, adaptation scale to assess the nature of mothers' interaction and patterns
      of psychosocial adaptation and depression scale to detect the presence of
      psychiatric disorders among the mothers. Only 35.0% of the mothers adapted
      positively to their child's condition; 62.9% of those had female children.
      Negatively adapted mothers were slightly older than positively adapted mothers
      and had more children. Maternal education and occupation were significantly
      associated with psychosocial adaptation. Knowledge of mothers about their child's
      condition significantly affected adaptation as well as the dependency of children
      in eating, drinking and sleeping. Two-thirds of mothers had high levels of
      psychopathology.

PMID- 20799534
TI  - Effect of group reminiscence therapy on depression in older adults attending a
      day centre in Shiraz, southern Islamic Republic of Iran.
AB  - The aim of this study was to examine the effectiveness of group reminiscence
      therapy on depression symptoms among elderly people attending a day centre in
      Shiraz, Islamic Republic of Iran. A sample of 49 people aged 60+ years
      participated in 6 group reminiscence sessions that were held twice weekly for a 3
      week period and completed a Farsi version of the 15-item geriatric depression
      scale. Mean depression scores decreased significantly from 8.18 (SD 1.20) before
      the intervention to 6.73 (SD 1.20) immediately after it and 7.55 (SD 1.19) 1
      month after the intervention. When analysed by demographic characteristics only
      marital status showed a statistically significant difference in depression scores
      comparing before and after the intervention.

PMID- 20799535
TI  - Proposal for a modernized Iranian notifiable infectious diseases surveillance
      system: comparison with USA and Australia.
AB  - This article reports on a comparative study of the national notifiable infectious
      diseases surveillance systems currently employed in the United States of America,
      Australia and the Islamic Republic of Iran, with the aim ofdeveloping a modified
      system specific to the needs of the Iranian health system. Features of the
      surveillance systems examined in each country included: official data gathering
      structures; types of data collected; case definition and classification criteria;
      data collection processes; data analysis methods; disease classification systems;
      data dissemination and distribution methods; data quality control; and
      confidentiality procedures and guidelines. After consolidating the data, a model
      for an Iranian notifiable infectious diseases surveillance system was developed
      and was tested by the Delphi method in 3 stages.

PMID- 20799536
TI  - [Helicobacter pylori infection in 755 patients with digestive complaints: Pasteur
      Institute, Morocco, 1998-2007].
AB  - We determined the prevalence of Helicobacter pylori infection in 755 patients
      with digestive complaints identified from laboratory records at the Pasteur
      Institute, Morocco from 1998 to 2007. Epidemiological factors and
      gastrointestinal conditions associated with this infection were also studied. All
      patients underwent endoscopy and diagnosis was by histology examination. The
      prevalence of H. pylori infection was 69%. The difference in prevalence between
      the age group 40-50 years and other age groups was statistically significant;
      gender had no significant association. H. pylori infection was found in 92% of
      chronic gastritis cases. The prevalence of H. pylori was significantly higher in
      the antrum (73%) than in the corpus (21%) and the pylorus (6%).

PMID- 20799537
TI  - Prevalence and antibiotic resistance of Pseudomonas aeruginosa isolated from
      swimming pools in northern Greece.
AB  - Pseudomonas aeruginosa is an important agent of opportunistic infection in
      aquatic environments. Our aim was to evaluate the occurrence and antimicrobial
      resistance of P. aeruginosa in the water of swimming pools in northern Greece.
      Water samples were obtained from hydrotherapy pools, jacuzzis/spas and swimming
      pools. A total of 16.6% (45/271) of the samples were positive for P. aeruginosa.
      Of the amenities examined, the most contaminated were hydrotherapy pools (25% of
      samples positive). A small percentage of isolates (20.0%) showed resistance to
      antibiotics. Compared with other studies, the prevalence of P. aeruginosa in
      swimming pools was relatively low, while the antibiotic resistance pattern of
      these community isolates was not high.

PMID- 20799538
TI  - Analysis of prescriptions dispensed at community pharmacies in Nablus, Palestine.
AB  - We investigated the prescription quality and prescribing trends of private
      clinicians in Nablus governorate, Palestine. A total of 363 prescriptions were
      collected from a random sample of 36 community pharmacies over a study period of
      288 working hours. Data regarding elements in the prescription and the types of
      drugs prescribed were analysed. Physician-related variables were mostly noted,
      however, patient's address and weight were absent in all prescriptions and less
      than half included age and sex. Information regarding strength of the medications
      prescribed was missing in over 70% of prescriptions. Other drug-related variables
      like frequency and instruction of use were present in over 80% of prescriptions.
      Antimicrobial agents were the most commonly prescribed followed by
      NSAIDs/analgesics. Amoxicillin alone or in combination was the most commonly
      prescribed antimicrobial agents followed by cefuroxime. Prescription writing
      quality in Nablus is deficient in certain aspects and improvement is required.

PMID- 20799539
TI  - Evaluation of the level of micronutrients in fortified foods in Alexandria,
      Egypt.
AB  - Food fortification is an effective, low-cost way to eliminate dietary
      micronutrient deficiencies in developing countries. This study in Egypt aimed to
      evaluate the levels of and variations in fortification with iron, iodine and
      vitamin A in food products from different manufacturers. Almost all iodized salt
      samples contained iodine concentrations within Egyptian standards. The iron
      content of iron-fortified biscuits supplied to schools and of vitamin-A-fortified
      margarine, infant formula milk powder and infant cereal food were highly variable
      and many samples were not within Egyptian standards. Monitoring of fortification
      levels of key products is required at the factory, retail and household levels.

PMID- 20799540
TI  - Dental visit patterns and periodontal treatment needs among Saudi students.
AB  - The aim of this study was to report on dental visit patterns and their
      association with periodontal health among young Saudi Arabian students. A
      representative sample of 3090 students was randomly selected. The students'
      dental visit patterns were assessed with a questionnaire. Clinical examinations
      were carried out using the community periodontal index of treatment needs. Age,
      sex and education level were significantly associated with the periodontal
      health. The prevalence of periodontal disease was significantly lower among
      subjects who were taught the right way to brush their teeth by the dentist. The
      highest occurrence of healthy periodontium (23.9%) and the lowest need for
      complex treatment (0%) were found among students who had annual reminders for
      check-ups (only 2.8% of the students).

PMID- 20799541
TI  - Update on mental health care in Lebanon.

PMID- 20799542
TI  - The focus of the World Health Day 2010 is on urbanization and health.

PMID- 20799543
TI  - Trialling diagnosis-related groups classification in the Iranian health system: a
      case study examining the feasibility of introducing casemix.
AB  - This paper examines the quality of routinely collected information in an Iranian
      hospital in a trial of casemix classification. Australian Refined Diagnosis
      Related Groups (AR-DRG) were used to classify patient episodes. There were 327
      DRGs identified, of which 20% had only 1 case. The grouper program identified
      invalid records for 4% of total separations. Approximately 4.5% of cases were
      classified into error DRGs and 3.4% were ungroupable. No complication and
      comorbidity effects were identified with 93% of total cases. R2 (variance in
      length of stay explained) was 44% for untrimmed cases, increasing to 63%, 57% and
      58% after trimming by L3H3, IQR and 10th-95th percentile methods respectively.

PMID- 20799544
TI  - Benefit-incidence analysis of government spending on Ministry of Health
      outpatient services in Jordan.
AB  - A benefit-incidence analysis was conducted for the year 2000 using various data
      sources including the Jordan healthcare utilization and expenditure survey 2000.
      The results illustrate that the poorest segment of the Jordanian population were
      the most likely to report sickness and seek treatment and were the main users of
      the Ministry of Health outpatient services. The poorest uninsured individuals
      were the main source of revenues generated through user fees. The targeting
      efficiency (i.e. total percentage of benefits received) for the poorest quintile
      was 33.8% compared with 4.0% in the richest quintile. The analysis demonstrates
      that the Jordanian government in-kind subsidy is reaching the poor.

PMID- 20799545
TI  - Surveillance of adverse events following immunization: 10 years' experience in
      Oman.
AB  - A descriptive record-based review of adverse events following immunization (AEFI)
      was carried out in Oman using the national database for the period 1996-2005. A
      total of 790 adverse event reports were received with an annual rate during the
      review period of 33.7 per 100 000 population or 10.8 per 100 000 doses
      administered. There were no reported deaths. The most frequently reported AEFI
      were BCG adenitis (69.7 per 100 000 doses) and local reactions (3.6 per 100 000
      doses respectively). The statistically significant higher rates among males, in
      children aged > 2 years and in some sparsely populated regions of Oman need
      further research. AEFI rates in Oman were similar or below the international
      averages

PMID- 20799546
TI  - Evaluation of HIV voluntary counselling and testing services in Egypt. Part 1:
      client satisfaction.
AB  - HIV voluntary counselling and testing (VCT) services were launched in Egypt in
      2005. A study of all functioning VCT centres in Egypt (7 mobile and 9 fixed)
      aimed to determine the profile of clients and their level of satisfaction to
      identify strengths and weaknesses in the service. In direct interviews with a
      sample of 928 clients, the main motive for seeking VCT was risky sexual behaviour
      (34.2%). More females than males sought services because of partners' risky
      sexual behaviour. More than 90% of the clients were satisfied with the
      counselling service. Only 41.4% were willing to discuss the test results with
      their partners. Male sex, higher education level and attendance at fixed VCT
      centres were associated with higher satisfaction.

PMID- 20799547
TI  - Evaluation of HIV voluntary counselling and testing services in Egypt. Part 2:
      service providers' satisfaction.
AB  - Voluntary counselling and testing (VCT) services are major components of HIV
      prevention and treatment efforts. A study in Egypt aimed to determine the
      satisfaction of service providers at VCTs to identify strengths and weaknesses in
      the service. Direct interviews with all 50 VCT team members and focus group
      discussions with 16 counsellors showed that the majority believed that they had
      received enough training (90%), but still 66% wanted further training. Only 50%
      reported receiving sufficient incentives. Problems that were highlighted included
      absence of a fixed job description, lack ofadministrative support, unclear
      working rules and regulations and lack of proper community awareness. Counsellors
      expressed the need for improving working environment to ensure privacy and
      confidentiality.

PMID- 20799548
TI  - Early experiences of abuse and current depressive disorders in Iranian women.
AB  - Early experience of abuse may be viewed as a risk factor for mental disorders in
      women later in life. This case-control study in Isfahan screened 709 women aged
      20-45 years using the Beck Depression Inventory and structured clinical
      interviews for Diagnostic Statistical Manual-IV criteria. Lifetime history of
      abuse was determined using a standard questionnaire. Among the women 35.1% had
      experienced fear of or actual abuse (physical, sexual or both) in childhood or
      adolescence. The risk of having major depression in adult life was significantly
      higher in women who experienced abuse in childhood and adolescence (OR 4.3),
      severe degrees of abuse (OR 3.9) or multiple forms of abuse (OR 3.8).

PMID- 20799549
TI  - Attention deficit-hyperactivity symptoms among Palestinian children.
AB  - We aimed to establish the prevalence and distribution of attention deficit
      hyperactivity disorder (ADHD) symptoms and other associated comorbid mental
      health problems in Palestinian schoolchildren. Thus 349 children aged 6-15 years
      were randomly selected from 23 schools in Gaza and the West Bank and were rated
      by their parents and teachers using both the ADHD DSM-IV Checklist and the
      Strengths and the Difficulties Questionnaire, which also measures conduct and
      emotional problems. There was a significant agreement between parents and
      teachers, with 4.3% of the children rated above the established cut-off scores on
      both the parent and teacher DSM-IV Checklist. Male gender, family size and living
      in an area of socioeconomic deprivation were independently associated with ADHD
      symptoms.

PMID- 20799550
TI  - Analysis of drug prescriptions in primary health care centres in Bahrain.

PMID- 20799551
TI  - Antibiotic use and knowledge in the community in Kalamoon, Syrian Arab Republic:
      a cross-sectional study.
AB  - Antibiotic misuse contributes to the growing problem of microbial resistance. To
      understand the current knowledge and practices regarding antibiotic use among
      Syrians, we conducted a cross-sectional study of 430 randomly selected adult
      residents of Kalamoon in the Syrian Arab Republic using a questionnaire. A high
      proportion (85%) had taken antibiotics in the past 4 weeks and 34% were not aware
      of the dangers of antibiotics. Of 365 participants, only 43% were prescribed the
      antibiotic by a physician to treat the condition, while 57% used an old
      prescription or took someone else's advice. Males, younger individuals, and those
      with low and medium income and lower educational status showed poorer practice
      and lower knowledge towards antibiotics. Educational efforts are needed to reduce
      patient demand for antibiotics.

PMID- 20799552
TI  - Knowledge, attitudes and practice of general practitioners towards complementary
      and alternative medicine in Doha, Qatar.

PMID- 20799553
TI  - Monitoring and enforcement of the salt iodization programme in Tabriz, Islamic
      Republic of Iran: a successful experience.
AB  - After a successful programme to prevent iodine deficiency disorders in the
      Islamic Republic of Iran in the 1990s and early 2000s, evidence emerged that
      urine iodine levels in the population were falling. This paper reviews efforts to
      monitor and enforce the iodization of salt production and shows the resulting
      improvements in iodization levels of factory table Salt and in urine iodine
      concentrations of primary-school children in East Azerbaijan province. Reaching
      targets for elimination of iodine deficiency disorders requires efficient
      monitoring of the population's iodine levels combined with monitoring of the
      iodine content of table salt and enforcement of iodization regulations.

PMID- 20799554
TI  - Spina bifida and birth outcome before and after fortification of flour with iron
      and folic acid in Oman.
AB  - This paper presents the trend of spina bifida and other neural tube defects in
      Oman after the nationwide implementation of folate supplementation of pregnant
      women in 1990 and the fortification of wheat flour with iron and folate in 1996.
      The annual incidence of spina bifida fluctuated from 2.34 to 4.03 per 1000
      deliveries between 1991 and 1996, but fell sharply to 2.11 per 1000 deliveries in
      1997, after which the downward trend continued, reaching 0.29 per 1000 deliveries
      by 2006. The rate of other neural tube defects remained almost constant. The
      reduction in spina bifida rates in Oman could be linked to the start of flour
      fortification but not the supplementation programme.

PMID- 20799555
TI  - [Infections with respiratory syncytial virus in North Lebanon--prevalence during
      winter 2008].
AB  - Between 1 December 2007 and 31 May 2008, we analysed 120 nasopharyngeal swabs for
      the presence respiratory syncytial virus (RSV) infection in 120 children aged 15
      days to 6 years, hospitalized in 2 hospitals in North Lebanon. Of the 120
      samples, 32 were positive (26.7%) for RSV. There was a peak in January which
      progressively disappeared from February to May. Being positive for RSV was
      significantly associated with the presence of rhinorrhoea and dyspnoea as
      clinical symptoms and the absence of pneumonia signs on chest X-ray and the
      diagnosis of bronchitises or bronchiolitis. Testing for RSV is important in cases
      of respiratory infections in children as it may limit unnecessary prescription of
      antibiotics.

PMID- 20799556
TI  - Nosocomial diarrhoea in relation to sanitation state: a study in Tikrit, Iraq.
AB  - A cross-sectional hospital-based study of 259 children aged < 5 years was carried
      out in Tikrit, Iraq, to identify the prevalence of nosocomial diarrhoea and
      sources of contamination in the ward environment. Nosocomial diarrhoea was
      diagnosed in 84 children (32.4%). Children with diarrhoea were more likely than
      unaffected children to be bottle-fed, given unboiled water, to have unclean food
      containers and contaminated bed sheets. Three out of 5 brands of formula milk
      (unopened cans) were contaminated. Three-quarters of medical staff and employees
      had contaminated hands. Enterobacter spp., Pseudomonas aeruginosa and Citrobacter
      spp. were the most commonly identified microorganisms. A greater emphasis on
      personal hygiene, improved care practices and promotion of breastfeeding is
      recommended.

PMID- 20799557
TI  - Estimation of birth weight by measurement of fundal height and abdominal girth in
      parturients at term.
AB  - in a prospective descriptive study, the usefulness of symphysis-fundal height and
      the product of abdominal girth and fundal height in predicting birth weight <
      2500 g and > 4000 g were examined. Fundal height and abdominal girth were
      measured at the time of admission on a sample of 795 parturient women at
      ateaching hospital in the Islamic Republic of Iran. Receiver operating
      characteristics curve analysis was used to select the best cut-off points. The
      product of abdominal girth x fundal height with the cut-off at 3900 g performed
      better for predicting birth weight > 4000 g, but for low birth weight, the
      regression model of fundal height with cut-off at 3000 g was a better predictor.

PMID- 20799558
TI  - Relationship between trait anxiety, dental anxiety and DMFT indexes of Turkish
      patients attending a dental school clinic.
AB  - The aims of this study were to evaluate possible relationships between trait
      anxiety, dental anxiety and the total number of decayed, missing and filled teeth
      (DMFT) index of patients attending a dental school clinic. A sample of 558
      patients was surveyed with the Turkish version of the Spielberger Trait Anxiety
      Inventory and Dental Anxiety Scale. DMFT index was calculated by clinical and
      radiographic examination. A significant linear correlation was observed between
      trait and dental anxiety, but there was no correlation between DMFT index, trait
      anxiety and dental anxiety. Trait anxiety has an impact on dental anxiety, but
      does not affect the DMFT index.

PMID- 20799559
TI  - Role of periodontitis in hospital-acquired pneumonia.
AB  - This study evaluated the role of periodontal pathogens in 50 hospitalized
      patients with hospital acquired pneumonia compared with 30 healthy controls.
      Specimens of oropharyngeal aspirate, dental plaque bronchoalveolar lavage and
      blood cultured 1 or more pathogens in around 80% of patients, predominatel 
      Staphylococcus aureus, followed by coagulase-negative staphylococci,
      Streptococcus pneumoniae and Klebsiell  pneumoniae. Antibiotic sensitivity
      patterns showed concordance of bacterial cultures from dental plaque an
      oropharyngeal cavity in 13 patients. C-reactive protein (CRP) levels were
      significantly higher in patients than ii controls and there was a significant
      correlation between serum and salivary CR1' levels. Dental plaque bioflln may
      promote oral and oronpharyngeal colonization of respiratory pathogens in
      hospitalized subiects.

PMID- 20799560
TI  - Mental and Social Health Atlas I in Saudi Arabia: 2007-08.
AB  - Based on the World Health Organization's Mental Health Atlas, the first Mental
      and Social Health Atlas in Saudi Arabia describes the historical background of
      mental health and social services in the country and identifies several
      deficiencies in the system including infrastructure and logistics and lack of
      epidemiological data. There is now great progress in strategic planning for
      developing and improving mental health care services across the nation, with
      suggestions to develop psychiatric services for identified special populations,
      to establish community mental health care services, to improve research and
      training in mental health, and to update mental health annual information systems
      using advanced information technology.

PMID- 20799561
TI  - Necrotizing fasciitis complicating female genital mutilation: case report.

PMID- 20799562
TI  - Prevalence of helminth ova in soil samples from public places in Shiraz.

PMID- 20799563
TI  - Sentinel surveillance for patients with acute hepatitis in Egypt, 2001-04.
AB  - Viral hepatitis is a major problem in Egypt. To define the epidemiology of the
      disease, sentinel surveillance was established in 5 hospitals in diverse areas of
      the country in 2001. Data were completed for patients meeting the case definition
      for viral hepatitis. Of a total of 5909 patients evaluated, 4189 (70.9%) showed
      positive antibody markers for hepatitis. Out of those, 40.2% had evidence of
      hepatitis A virus (HAV) infection, 30.0% hepatitis B virus (HBV) and 29.8%
      hepatitis C virus (HCV) infection. This surveillance system was useful in
      identifying the variable endemicity of acute HAV infection in different regions
      and for better understanding the epidemiology of HBV and HCV infection.

PMID- 20799564
TI  - The need for a comprehensive response to HIV/ AIDS in north-western Somalia:
      evidence from a seroprevalence survey.
AB  - The prolonged civil strife in the North-West Zone of Somalia (Somaliland) has
      hampered the development of social infrastructure and public health services.
      There are limited data on HIV/AIDS. In 2004, a sentinel HIV seroprevalence survey
      was conducted. Blood samples were collected from 1561 women attending antenatal
      care clinics, 249 tuberculosis (TB) patients and 243 people attending sexually
      transmitted disease (STD) clinics. Samples were tested for syphilis and HIV.
      Overall HIV prevalence was 1.4%, significantly higher than that observed in many
      other countries in the Region. Prevalence was 1.2% among pregnant women 15-24
      years, 12.3% among patients with STD and 5.6% among TB patients. The prevalence
      of syphilis was 1.3% in the pregnant women.

PMID- 20799565
TI  - Antimalarial drugs: availability and mode of prescribing in Mukalla, Yemen.
AB  - Malaria is one of the top health problems in Yemen. This study was done to
      evaluate the availabilit and prescribing of antimalarial drugs in Al-Mukalla
      city, based on the treatment guidelines of the National Malari Control Programme
      (NMCP). Chloroquine, quinine and sulfadoxine/pyrimethamine were the most availabl
      and prescribed antimalarial drugs in all 60 pharmacies (government and private)
      in the city. Of 42 prescriptions Sanalysed, 54.2% did not comply with NMCP
      guidelines on appropriate dose and duration, especially those prescribed by GPs:
      16.7% contained more than 1 antimalarial drug. More efforts are needed to educate
      physicians Sabout the NMCP treatment guidelines and to deter pharmacies from
      random selling of antimalarial drugs.

PMID- 20799566
TI  - Indicators of rational drug use and health services in Hadramout, Yemen.
AB  - WHO standard indicators of rational drug use, this study analysed 550
      prescriptions from 20 health facilities at different levels throughout Hadramout
      governorate, Yemen. A mean of 2.8 (SD 0.2) drugs were prescribed per
      prescription, with a low rate of prescribing drugs by generic name (39.2%). The
      proportion of prescriptions for antibiotics was 66.2%, for injectable drugs 46.0%
      and for vitamins/tonics 23.6%. The essential drugs list was available in 78.9% of
      facilities and a high percentage of drugs were prescribed from the list (81.2%).
      Other official sources of local drug information were less available.

PMID- 20799567
TI  - Smoking among male medical sciences students in Semnan, Islamic Republic of Iran.
AB  - We determined the prevalence of smoking among 320 male medical sciences students
      (174 studying for a medical degree, 95 a bachelor degree and 51 a associate
      degree) in Semnan, Islamic Republic of Iran. A self-administrated, anonymous
      questionnaire was used. The prevalence of smoking was 14.4%; 45.6% of the smokers
      started smoking between the ages of 18 and 20 years, 43.5% starting at
      university. There was no significant difference in the prevalence between
      students undertaking different college degrees and also those having different
      types of accommodation. However the smoking behaviour of friends and family was
      significantly correlated with smoking in the students. Smoking amongst medical
      sciences students, who will become the health professionals of the future, needs
      to be addressed.

PMID- 20799568
TI  - Effect of smoking on the response to nonsurgical periodontal therapy.
AB  - To investigate the influence of smoking on the response of nonsurical periodontal
      treatment, at prospective study was carried out on 65 smokers and 68 nonsmoker
      controls. Both groups were examined periodontally for plaque, bleeding and loss
      of attachment, before and after a course of treatment with oral hygiene
      instructions, scaling, root planning periodontal and polishing. Before treatment,
      mean bleeding index score was significantly higher in smokers than nonsmokers but
      scores were similar after treatment. Plaque index scores were similar in both
      groups before and after treatment. Loss of attachment score was significantly
      higher in smokers before treatment and remained higher after treatment. Smokers
      showed more signs of periodontal disease, and treatment did not reverse this
      fully.

PMID- 20799569
TI  - Clinical and epidemiological characteristics of lung cancer cases in Qatar.
AB  - This study documents for the first time the clinical and epidemiological
      characteristics of lung cancer cases in Qatar from 1998 to 2005. The age
      standardized incidence rate was higher than that in many other Gulf countries:
      8.95 per 100,000 (15.2 per 100,000 for males; 3.95 per 100,000 for females). Mean
      age at diagnosis was 57.5 years. Most patients were current smokers or ex-smokers
      at the time of diagnosis (82.5%). Unlike other Gulf countries, adenocarcinoma was
      the predominant type in both Qatari nationals and expatriates (43.9% of lung
      cancer types). Many cases were in an advanced stage at diagnosis (64.2% at stage
      IV). Incomplete information was available on mortality rate due to the migration
      of expatriates.

PMID- 20799570
TI  - Adherence of primary care physicians in Aseer region, Saudi Arabia to the
      National Protocol for the Management of Asthma.
AB  - To determine adherence of primary health care (PHC) physicians to the National
      Protocol for the Management of Asthma and barriers affecting adherence, we
      conducted a cross-sectional study in Aseer region, Saudi Arabia. Sixty-one PHC
      physicians completed self-administered questionnaires on the protocol
      recommendations. We also checked 212 medical records for adherence. Despite high
      awareness among the physicians, adherence to the protocol was low: perceived
      barriers included lack of essential medications, insufficient time and lack of
      training on the protocol. We recommend establishing a new strategy for effective
      training of PHC physicians on the protocol.

PMID- 20799571
TI  - Outcomes of total versus subtotal abdominal hysterectomy.
AB  - There is still controversy about the best technique for hysterectomy to reduce
      postoperative adverse effects. This randomized clinical study in Babol, Islamic
      Republic of Iran, compared some clinical complications and sexual functioning
      following subtotal (SAH) and total abdominal hysterectomy (TAH). A total of 150
      women (50 allocated to SAH and 100 to TAH) were followed up at 6 months
      postoperatively. Length of hospitalization was 4.40 (SD 1.90) days after SAH and
      4.48 (SD 1.67) days after TAH. Haemoglobin level, postoperative fever, symptoms
      of dyspareunia and frequency of sexual intercourse were not significantly
      different between the 2 groups of women. SAH did not show any significant
      benefits over TAH.

PMID- 20799572
TI  - Complementary feeding patterns in a developing country: a cross-sectional study
      across Lebanon.
AB  - This first, large-scale study on complementary feeding in Lebanon analysed the
      timing and types of food introduced to infants according to mothers' demographic
      and socioeconomic and infants' characteristics. A cross-sectional survey over 10
      months found that the majority of infants were introduced to solid foods at or
      after 4 months of age. A large number of infants were given liquids other than
      breast or formula milk earlier. Women in employment outside the home were almost
      twice as likely to introduce solid foods before age 4 months. The most common
      starting food was cereals. More than half the children consumed starchy foods and
      fruits every day, but not meats and fish.

PMID- 20799573
TI  - Nutritional interventions in refugee camps on Jordan's eastern border: assessment
      of status of vulnerable groups.
AB  - This study was carried out on refugees who had fled the turmoil in Iraq and were
      hosted atthe eastern border of Jordan. We assessed the nutritional status of 325
      children aged 6 months-10 years and 452 females aged 10-72 years, and evaluated
      the food rations supplied by the UNHCR. Dietary, anthropometric and laboratory
      indicators were determined. For females and children respectively, prevalence
      rates were: anaemia 45% and 75%, iron deficiency 44% and 64%, and vitamin A
      deficiency 6% and 28%. Rationed foods supplied little of some micronutrients:
      only 33% of vitamin A needs were met. Dietary supplementation for refugees in
      camps is always warranted.

PMID- 20799574
TI  - Practices in child growth monitoring in the countries of the Eastern
      Mediterranean Region.
AB  - Growth reference charts are among the most sensitive and valuable tools for
      assessing the health and development of children. A questionnaire survey was
      answered by 16 of the 21 ministries of health in the Eastern Mediterranean Region
      countries (EMR) about their use of growth charts for children under 5 years. Most
      of the countries (13/16) used the NCHS/WHO charts and weight-for-age was the most
      commonly used. Charts for height-for-age and head circumference-for-age were less
      commonly used. Problems in the use of charts were identified. The introduction of
      the new WHO Child Growth Standards, based on exclusively breastfed babies, is a
      unique opportunity to support growth monitoring and optimal feeding practices in
      EMR.

PMID- 20799575
TI  - Effect of breastfeeding on cognitive performance in a British birth cohort.
AB  - This cohort study investigated the effect of early life nutrition on later
      performance in developmental milestones and cognitive tests. Structural equation
      modelling was carried out on follow-up data from a national birth cohort of 5362
      children born in 1 week of 1946 in Britain. Children who were breastfed longer
      showed earlier developmental milestones. After adjusting for sex, social group
      and milestones, those children scored higher in verbal tests. Path analysis
      showed that breastfeeding may have an effect even into adult life. The chain of
      path coefficients from breastfeeding to developmental milestones at early ages,
      to cognitive scores at ages 8-15 years, to reading tests at age 26 years and to
      memory and visual tests at age 43 years were significant in females but not in
      males.

PMID- 20799576
TI  - Prevalence of skin disorders among primary-school children in Baghdad
      governorate, Iraq.
AB  - To determine the prevalence of skin diseases among primary-school children in
      Baghdad, Iraq, a total of 2160 schoolchildren were randomly selected from 30
      primary schools. Sociodemographic data were collected from each pupil and exposed
      parts of the body of each child were clinically examined. The overall prevalence
      of skin diseases was 40.9%. A significant association between the prevalence of
      skin diseases with education level of parents was demonstrated. The prevalence
      rates of transmissible and nontransmissible skin diseases were 8.8% and 33.7%
      respectively. The high prevalence rate may reflect prevailing low socioeconomic
      conditions.

PMID- 20799577
TI  - Ambiguous genitalia in neonates: a 4-year prospective study in a localized area.
AB  - This study aimed to determine the possible etiology ot ambiguous genitalia in 41
      newborn intants at a referral hospital in Hofuf city, Saudi Arabia. In 46,XX
      karyotype patients (n 14), congenital adrenal hyperplasia and general
      malformation disorder were the most common causes of genital ambiguity, while in
      46,XY karyotype patients (n=18), testosterone pathway biosynthetic defect was the
      most common cause even in conjunction with a generalized malformation disorder.
      In patients with abnormal karyotype (n=3), 1 had trisomy 18 (47,XX) and died
      after 3 months and 2 had different types of mosaic Turner syndrome. The karyotype
      was undetermined in 6 natients. Positive family history of ambiguous genitalia
      was noted in 4 patients.

PMID- 20799578
TI  - Validity of pulse oximetry in detection of hypoxaemia in children: comparison of
      ear, thumb and toe probe placements.
AB  - This study of paediatric intensive care patients aimed to determine where pulse
      oximetry probes shouid be placed to obtain the most accurate and reliable
      readings of peripheral oxygen saturation (SpO2). Using arterial blood gas
      analysis (SaO2) as the gold standard and SpO2 92% and SaO2 < 90% as indicators of
      hypoxaemia, negative predictive values of SpO2 were 96%, 98% and 98% at the ear,
      thumb and big toe respectively in 110 children, and 93% at all 3 sites in 90
      neonates. The highest clinical agreement between SaG, and SpO2 was for ear probes
      in children (kappa = 0.70) and the lowest was for big toe probes (kappa = 0.57
      and 0.28 in children and neonates respectively).

PMID- 20799579
TI  - Coverage of and barriers to routine child vaccination in Mukalla district,
      Hadramout governorate, Yemen.
AB  - To determine the vaccination coverage for children 12-23 months and to identify
      reasons for nonvaccination, we conducted a community-based survey in Al Mukalla
      district. Information about vaccination status and related barriers was collected
      for 210 children: 82% were fully vaccinated, 12% were partially vaccinated, and
      5% were not vaccinated. Drop-out rate between DPTI and DPT3 was 3.1%. Combining
      the evidence of vaccine cards and parent's history, the coverage for OPV1 was
      94.3%, OPV3 91.4%, measles 90%, and BCG 88.1%. Reasons for not vaccinating
      included lack of information (54%) and existence of obstacles (35%). There is a
      need to raise the awareness of families about vaccination and to expand
      continuous outreach sessions to cover all children.

PMID- 20799580
TI  - Causes and anatomical site of blindness and severe visual loss in Isfahan,
      Islamic Republic of Iran.
AB  - This study in 2005 evaluated the causes and major anatomical site of blindness
      and severe visual loss at a school for blind children in Isfahan province,
      Islamic Republic of Iran. All 211 students were examined according to the
      modified WHO/PBL eye examination record: 70.4% were blind, 24.3% had severe
      visual loss and 5.3% were visually impaired. The major causes of abnormality were
      hereditary factors (42.7%), prenatal/neonatal (18.5%) and unknown etiology
      (35.5%). The main sites of abnormality were the retina (62.6%), whole globe
      (17.5%), lens (7.1%) and optic nerve (7.1%). A high proportion of parents were in
      a consanguineous marriage (49.2%). The pattern of blindness in Isfahan
      encompasses characteristics of both developed and developing countries.

PMID- 20799581
TI  - Five-minute preparation of platelet-poor plasma for routine coagulation testing.
AB  - Clinical and Laboratory Standard Institute guidelines require that routine
      coagulation tests are performed with platelet-poor plasma (< 10,000
      platelets/microL) and prepared from whole citrated blood centrifuged at low speed
      for 10-30 minutes. To compare results obtained from plasma centrifuged for 5
      minutes at 3000 g or for 10 minutes at 2000 g, 46 blood samples from normal
      healthy adults were assayed for prothrombin time, international normalized ratio
      and activated partial thromboplastin time. No significant differences were found
      in test results and it was concluded that 5 minutes centrifugation at 3000 g is a
      reliable and useful option to reduce the turnaround time for these tests.

PMID- 20799582
TI  - Case of postoperative haematometra in a 40-year-old woman.

PMID- 20799583
TI  - Cholera outbreak in Baghdad in 2007: an epidemiological study.
AB  - In 2007 there was an epidemic of cholera in Iraq with 4667 cases. The first case
      in Baghdad was diagnosed on 19 September 2007 and the last case on 13 December
      2007. In all, 136 cases were reported (2.9% of the country total) in 6 of the 13
      districts of Baghdad. The median age of the cases was 11 years (range = 0.3-71
      years). There were 3 deaths giving a case fatality rate of 2.2%. Bacteriological
      testing confirmed that the outbreak was caused by Vibrio cholerae O1, biotype El
      Tor, serotype Inaba. The strain was resistant to trimethoprim-sulfamethoxazole,
      but sensitive to tetracycline and chloramphenicol. Efforts are needed in Baghdad
      to establish safe drinking-water and proper sanitation as limited availabilty of
      tap-water and sewage contamination probably contributed to the spread of the
      disease.

PMID- 20799584
TI  - Burden of Haemophilus influenzae type b disease in Pakistani children.
AB  - Estimates of the burden of Haemophilus influenzae type b (Hib) in children in
      Pakistan are limited. A prospective surveillance was set up in 8 sentinel sites
      in Karachi and Hyderabad in January 2004. A total of 1481 children aged < 5 years
      underwent lumbar puncture for suspected acute bacterial meningitis. Specimens
      from 237 (16.0%) children met the criteria for probable bacterial meningitis, and
      Hib was detected in 45 of them (19.0%). The minimum detected incidence of Hib
      meningitis in the Hyderabad area was 7.6 per 100 000 in children < 5 years of
      age, and 38.1 per 100 000 children < 1 year. Hib vaccination is justified for
      inclusion in Pakistan's expanded programme of immunization.

PMID- 20799586
TI  - [Cost effectiveness analysis of screening strategies for cervical cancer in
      Tunisia].
AB  - We aimed to identify the most appropriate screening strategy for cervical cancer
      (periodicity of 3, 5 or 10 years) for Tunisia, taking into consideration the
      incidence of the disease, costs of screening and economic implications. We
      simulated follow-up of a fictitious cohort of 1 million women 35-39 years over 30
      years. Computation of yearly medical care costs was based on data from medical
      files of patients diagnosed with cervical cancer in 2004 at the National
      Institute of Cancer, Tunis. For a 60% coverage level of screening, cervical
      cancer reduction would be 49.2% for a 3-year periodicity. The reduction would be
      40.3% and 33.1% for 5 and 10 years periodicity respectively. Considering cost
      effectiveness, 10-year screening gave the lowest annual cost to avoid 1 cervical
      cancer case.

PMID- 20799585
TI  - Fever prevalence and management among three rural communities in the North West
      Zone, Somalia.
AB  - Between March and August 2008 we undertook 2 cross-sectional surveys among 1375
      residents of 3 randomly selected villages in the district of Gebiley in the North
      West Zone, Somalia. We investigated for the presence of malaria infection and the
      period prevalence of self-reported fever 14 days prior to both surveys. All blood
      samples examined were negative for both species of Plasmodium. The period
      prevalence of 14-day fevers was 4.8% in March and 0.6% in August; the majority of
      fevers (84.4%) were associated with other symptoms including cough, running nose
      and sore throat; 48/64 cases had resolved by the day of interview (mean duration
      5.4 days). Only 18 (37.5%) fever cases were managed at a formal health care
      facility: 7 within 24 hours and 10 within 24-72 hours of onset. None of the
      fevers were investigated for malaria; they were treated with antibiotics,
      antipyretics and vitamins.

PMID- 20799587
TI  - Hyperglycaemia, hypertension and their risk factors among Palestine refugees
      served by UNRWA.
AB  - UNRWA's noncommunicable disease screening activities were evaluated among 7762
      refugees screened for hypertension and type 2 diabetes in Jordan, Syrian Arab
      Republic, Lebanon, Gaza Strip and West Bank in June 2007. People were referred
      for screening most commonly because of age (both sexes), followed by smoking
      (males) and family history (females). Atotal of 9% ofscreened people were
      diagnosed with hypertension/ diabetes. Being older than 40 years, obese or with a
      positive family history of diabetes or cardiovascular disease increased the risk
      of presenting with hypertension and/or hyperglycaemia 3.5, 1.6 and 1.2 times
      respectively. Differences in risk factor detection and screening outcome in
      relation to differences in lifestyle are discussed.

PMID- 20799588
TI  - Comparison of artificial neural network and binary logistic regression for
      determination of impaired glucose tolerance/diabetes.
AB  - Models based on an artificial neural network (the multilayer perceptron) and
      binary logistic regression were compared in their ability to differentiate
      between disease-free subjects and those with impaired glucose tolerance or
      diabetes mellitus diagnosed by fasting plasma glucose. Demographic,
      anthropometric and clinical data were collected from 7222 participants aged 30-88
      years in the Tehran Lipid and Glucose Study. The kappa statistics were 0.229 and
      0.218 and the area under the ROC curves were 0.760 and 0.770 for the logistic
      regression and perceptron respectively. There was no performance difference
      between models based on logistic regression and an artificial neural network for
      differentiating impaired glucose tolerance/diabetes patients from disease-free
      patients.

PMID- 20799589
TI  - Control of diabetes mellitus in the Eastern Province of Saudi Arabia: results of
      screening campaign.
AB  - To assess the status of diabetes mellitus (DM) control in the Eastern province of
      Saudi Arabia, all Saudi Arabian residents aged 30 years and above were invited to
      participate in a screening campaign. Of 197 681 participants screened 15.7% had a
      previous diagnosis of DM. Sociodemographic and clinical data were collected from
      these patients. Only 33.8% of patients were achieving their glycaemic control
      target (fasting or random capillary blood glucose < 130 mg/dL or < 180 mg/dL
      respectively). Multiple logistic regression analysis showed that higher age,
      current smoking and lower level of physical activity were significantly
      associated with uncontrolled DM. Hypertension was positively associated with
      glycaemic control. The overall rate of diabetes control is unacceptably low in
      the general population of this province.

PMID- 20799590
TI  - [Exclusive breastfeeding and mixed feeding: knowledge, attitudes and practices of
      primiparous mothers].
AB  - We assessed the knowledge attitudes and practices of primiparous women with
      regard to exclusive breastfeeding and the use of formula milk. A total of 260
      women were interviewed and the results showed that 41.5% of the women breastfed
      exclusively while 58.5% bottle-fed only or did so together with breastfeeding. Of
      those who breastfed, 43.0% did not do so soon after giving birth and did not know
      about colostrum. Overall, the knowledge, attitudes and practices of the mothers
      were unsatisfactory concerning the golden rules for successful breastfeeding, the
      ideal duration of exclusive breastfeeding and the food to include when
      introducing complementary feeding. This might be due to a low level of schooling
      and information, hence the need for improving strategies for maternal care during
      the antenatal and postnatal periods.

PMID- 20799591
TI  - Predictors of gestational diabetes mellitus in a high-parity community in Saudi
      Arabia.
AB  - A study in Riyadh, Saudi Arabia investigated the prevalence of gestational
      diabetes mellitus (GDM) and its predictors in a high-parity group of pregnant
      women (n = 633, 50.1% grand multiparas). The prevalence of GDM was 12.5% and 3.8%
      by World Health Organization and American Diabetes Association criteria
      respectively. Multiparous women were 8.29 times more likely to have GDM than
      nulliparous women. However, after adjustment for maternal age and history of
      abortion, nulliparous women were 2.95 times more likely to develop GDM than
      parous women. The probability of GDM for a parous woman increased from 2% to 21%
      when age increased from 20 to 40 years. The high rate of GDM among grand
      multiparas may be due to the confounding effect of maternal age.

PMID- 20799592
TI  - Evaluation of effect of silymarin on granulosa cell apoptosis and follicular
      development in patients undergoing in vitro fertilization.
AB  - To investigate the effects of silymarin on follicular development, we enrolled 40
      healthy women undergoingin vitro fertilization (IVF) due to male factor
      infertility in this trial. They underwent ovulation induction and on a random and
      blind basis, patients were assigned to receive silymarin (70 mg x 3/day) or
      placebo from the beginning of the induction cycle. The number and quality of
      oocytes retrieved were evaluated and apoptosis of > or = granolusa cells was
      studied. There was no significant difference between the groups for mean number
      of follicles 18 mm (P = 0.131), mean number of oocytes retrieved (P = 0.209) or
      endometrial thickness (P = 0.673). However, the proportion of total apoptosis in
      the study group was significantly lower than in the placebo group (P = 0.032).
      These data suggest that administration of silymarin in IVF patients concomitantly
      with gonadotropin results in reduction of granolusa cell apoptosis but does not
      have any effect in promotion of follicular development, oocyte retrieval or
      endometrial thickness.

PMID- 20799593
TI  - Insulin-like growth factor-1 and zinc status of goitrous primary-school children
      in Arak, Islamic Republic of Iran.
AB  - Despite a successful national salt iodinization programme, endemic goitre still
      persists in Iranian children. In a cross-sectional study in Arak the prevalence
      of goitre was 5.2% in a sample of 6520 primary-school children. Subsamples of 193
      children with goitre and 151 healthy children were assessed for urinary iodine
      excretion, thyroid hormone profile, insulin-like growth factor-1 (ICF-1) and
      serum zinc. The mean urinary iodine levels of goitrous children and healthy
      children were 17.4 microg/dL and 15.3 microg/dL respectively, suggesting that
      iodine consumption was adequate. No significant differences were found between
      goitrous and healthy schoolchildren in mean levels of urinary iodine, serum IGF-1
      or serum zinc. Other factors need be evaluated to, explain the residual
      prevalence of goitre.

PMID- 20799594
TI  - Prevalence of asthma among schoolchildren in Ahvaz, Islamic Republic of Iran.
AB  - The prevalence of asthma was determined in a random sample of schoolchildren in
      Ahvaz city, southwest Islamic Republic of Iran, based on the International Study
      of Asthma and Allergy in Childhood (ISAAC) protocol. The prevalence of ever
      wheeze and current wheeze was 11.1% and 7.4% among 1410 children aged 6-7 years
      (parent-reported) and 17.7% and 10.3% among 1450 children aged 13-14 years (self
      reported). The prevalence of ever asthma was significantly higher among 13-14
      year-olds (9.8%) than 6-7-year-olds (6.8%) but no significant difference was
      found between males and females in either age group. Comparisons are made with
      other Iranian cities and international data.

PMID- 20799595
TI  - Prevalence of overweight and obesity among adolescents in Irbid governorate,
      Jordan.
AB  - Overweight and obesity is an escalating health problem in both developed and
      developing countries. This descriptive cross-sectional study aimed to determine
      the prevalence of overweight and obesity among adolescents aged 13-16 years in
      Irbid governorate, Jordan, and to compare the prevalence by sex, residential area
      and socioeconomic status. In a cluster random sample of 1355 school students the
      prevalence of overweight and obesity (body mass index > or = 85th percentile) was
      24.4% (15.7% overweight and 8.7% obese) and was significantly higher among female
      students, students who lived in urban areas and those with working parents. This
      high prevalence of overweight is a serious concern for public health in Jordan.

PMID- 20799596
TI  - Could the employment-based targeting approach serve Egypt in moving towards a
      social health insurance model?
AB  - The current health insurance system in Egypt targets the productive population
      through an employment-based scheme bounded by a cost ceiling and focusing on
      curative care. Egypt Social Contract Survey data from 2005 were used to evaluate
      the impact of the employment-based scheme on health system accessibility and
      financing. Only 22.8% of the population in the productive age range (19-59 years)
      benefited from any health insurance scheme. The employment-based scheme covered
      39.3% of the working population and was skewed towards urban areas, older people,
      females and the wealthier. It did not increase service utilization, but reduced
      out-of-pocket expenditure. Egypt should blend all health insurance schemes and
      adopt an innovative approach to reach universal coverage.

PMID- 20799597
TI  - Prevalence of current smoking in Eastern province, Saudi Arabia.
AB  - All Saudi Arabian residents of the Eastern province of Saudi Arabia aged 30+
      years completed a structured interview questionnaire about smoking. The
      prevalence of current smoking (smoked > 100 cigarettes or any tobacco products
      including waterpipe in lifetime and still smoking daily or occasionally for 1
      month or more) among 196 268 respondents was 16.9% (28.7% among men and 4.5%
      among women). There was a significantly higher prevalence of smoking at younger
      ages in men and older ages in women. Multiple logistic regression analysis showed
      that factors independently associated with smoking were lower socioeconomic
      tatus, lower education, being divorced and occupations such as the military and
      self-employed.

PMID- 20799598
TI  - Burden of smoking in Moroccan rural areas.
AB  - The aim of this study was to estimate the prevalence and characteristics of
      current smoking among rural Moroccans. The population study included 3438
      individuals aged 15 years and above from both sexes. The crude prevalence of
      current smoking (currently smoked and had smoked > 100 cigarettes in lifetime)
      was 16.9% in the adolescent and adult rural population: 31.0% among men and 1.1%
      among women. The majority of smokers 74.4% of men and 68.8% of women) began
      smoking before age 20 years. Multiple logistic regression analysis showed that
      age, sex, marital status, occupation and region of residence were the strongest
      determinants of current smoking. These results showed a high prevalence of
      smoking among males in the rural population of Morocco.

PMID- 20799599
TI  - Implementing a gatekeeper system to strengthen primary care in Egypt: pilot
      study.
AB  - Overuse of hospital outpatient clinics in Egypt, due to lack of an effective
      gatekeeper system, has threatened the sustainability of improved primary care
      services. In this pilot project in Menoufia in the Nile delta region, the price
      of direct hospital outpatient visits was increased, encouraging patients to
      attend primary care clinics first. As a result, direct hospital outpatient
      utilization decreased by 63% in the project area compared with a 4% increase in a
      control district. The majority of this reduction was accounted for by patients
      attending either public primary care clinics or private clinics. Increasing the
      price of direct hospital outpatient visits was an effective way to establish a
      gatekeeper role for family health clinics.

PMID- 20799600
TI  - Triage systems: a review of the literature with reference to Saudi Arabia.
AB  - This review evaluates some of the international literature on triage in order to
      provide evidence-based data for the medical community in Saudi Arabia
      specifically and the Eastern Mediterranean Region in general. The aim is to
      encourage national health planners and decision-makers to apply formal triage
      systems in the emergency departments of general and specialist hospitals and
      other relevant health settings, including primary and psychiatric care. Research
      and training on triage is extremely limited in Saudi Arabia and the Region and
      this review highlights the need for more research on triage systems and for the
      inclusion of training on triage in medical education programmes.

PMID- 20799601
TI  - Pseudo-Bartter as an initial presentation of cystic fibrosis. A case report and
      review of the literature.

PMID- 20799602
TI  - First report on Leishmania major/HIV coinfection in a Sudanese patient.

PMID- 20799603
TI  - [Free amino acids and reducing sugars in the freshwater shrimp Gammarus lacustris
      (Crustacea, Amphipoda) at the initial stage of preparation to winter season].
AB  - A peculiarity of amino acid profile of the cold-resistant freshwater shrimp
      Gammarus lacustris in the beginning of autumn is a high level of ornithine, the
      second after alanine (17.0 +/- 1.4 and 22.6 +/- 1.4 micromol/ml of homogenate,
      respectively). The amount of alanine and ornithine accounts for 39.8% of the
      total pool of free amino acids and together with lysine and leucine - 55%. Free
      glucose is the major reducing sugar (6.42 +/- 0.78 micromol/ml).

PMID- 20799604
TI  - [Peculiarities of organization of tissue metabolism in molluscs with different
      tolerance to external hypoxia].
AB  - Oxygen consumption, content of several carbohydrate metabolites, and activities
      of their coupled enzymes were studied in bivalve molluscs with different
      tolerance to oxygen deficit: Mytilus galloprovincialis Lam. (black morpha) and
      Anadara inaequivalvis Br. It has been shown that under conditions of external
      normoxia the anadara resistance to hypoxia preserves anaerobic orientation of
      metabolism. Its tissues are distinguished by high activities of malate and
      lactate dehydrogenases with the decreased content of glucose and the increased
      level of lactate. In several organs the succinate thiokinase and fumarate
      reductase reactions are realized, which is indicated by elevated activities of
      the alanine and aspartate aminotransferases. The anaerobic orientation of protein
      metabolism is added by a high pool of free aminoacids and the elevated urea
      content in the molluscs tissues. The total orientation of metabolism in the
      anadara tissues rules out a significant lactate accumulation and determines low
      requirements of its organism in oxygen.

PMID- 20799605
TI  - [Comparative enzymological study of catalytic properties of liver monoamine
      oxidases in frogs].
AB  - Comparative enzymological study of catalytical properties of monoamine oxidase
      (MAO) of liver of the lake frog Rana ridibunda and brown frog Rana temporaria has
      revealed certain features of similarity and differences between these enzymes.
      The MAOs from both studied biological sources show catalytic properties
      resembling those of the classical MAO of terrestrial vertebrates: they deaminate
      tyramine, tryptamine, serotonin, benzylamine and do not deaminate histamine, have
      sensitivity to chlorgiline, the specific inhibitor of the MAO A form, and
      deprenyl, the specific inhibitor of the MAO B form, and are not inhibited with
      10(-2) M semicarbazide. Based on data of substrate-inhibitor analysis, a
      suggestion is put forward about the existence of two molecular forms of the
      enzyme in liver of the studied frog species. Interspecies quantitative
      differences have been revealed between liver MAO of Rana ridibunda and Rana
      temporaria in values of kinetic parameters of reactions of deamination of several
      substrates and in sensitivity to the inhibitors, deprenyl and clorgyline. In the
      species Rana temporaria the MAO activity in reaction of deamination of serotonin
      and benzylamine were practically identical, whereas in the species Rana ridibunda
      these parameters for serotonin were almost one order of magnitude higher than for
      benzylamine. For the species Rana ridibunda, selectivity of action of deprenyl
      was expressed many times weaker while selectivity of the chlorgiline--one order
      of magnitude stronger than for the species Rana temporaria. The catalytic
      activity for all studies substrates of liver MAO of both studied amphibian
      species were several times lower as compared with the enzyme of rat liver.

PMID- 20799606
TI  - [Correlation of phospholipid composition and physicochemical characteristics of
      lipids in tissues of the root vole Microtus oeconomus of different ages].
AB  - There was performed a comparative analysis of phospholipids and of lipid
      physicochemical characteristics in spleen, blood erythrocytes, and liver of the
      root voles caught in the natural environmental habitation at different phases of
      the population cycle, as well as of the animals born and raised throughout the
      entire life in vivarium, depending on the animals' sex and age. The age-related
      changes in the phospholipid composition have been established to correlate with
      lipid physicochemical characteristics, while the scale and direction of the
      changes depend on the tissue functional role, the initial level of the
      antioxidative activity (AOA) of its lipids, and sex of the animals. In the
      process of the organism aging, parameters of the system of regulation of lipid
      peroxidation change not unidirectionally; in group of animals of the same age,
      individuals with different biochemical characteristics can be present. Under
      natural conditions of habitation the degree of expression of age-related changes
      is modified by populational factors.

PMID- 20799607
TI  - [Sex-related peculiarities of conditioned reflex activity and dynamics of sex
      steroids in the brain].
AB  - Sexual peculiarities of dynamics of brain sex steroids in the process of learning
      and extinction of the conditioned reflex of passive avoidance have been studied
      in model experiment. Prior to learning of conditioned reflex, females were found
      to be distinguished by manifestation of anxiety and fear as compared with males.
      At formation of the conditioned reflex, no significant sex differences were
      detected between males and females, whereas extinction of the conditioned
      reaction of passive avoidance in rat males occurred by 2-3 days faster than in
      females. At learning of conditioned reaction of passive avoidance, in sexually
      mature rat males there was revealed an increase of the testosterone content in
      various brain structures, especially in hippocampus and frontal cortex, while its
      level in blood plasma remained unchanged. Also shown was an elevation of
      estradiol concentration in female amygdale, whereas at extinction of the
      conditioned reaction of passive avoidance, a rise of estradiol values was noted
      in hippocampus and cingular cortex. At the same time the testosterone level in
      blood plasma did not change, whereas the estradiol concentration decreased
      statistically significantly after extinction of the conditioned reflex. Different
      dynamics of changes of the sex steroid levels in brain and blood plasma can
      indicate a probability of their formation in the nervous tissue. The performed
      correlation analysis confirms the concept of selective involvement of
      testosterone and estradiol of specific brain structures in realization of the
      process of learning and memory in sexually mature rat males and females.

PMID- 20799608
TI  - [Preadaption to nitrogen anesthesia and impairment of brain cortex structure in
      rats during hypoxia].
AB  - The attenuating effect of various variants of hypoxia on hyperbaric anesthesia in
      rats was studied. The most efficient turned out to be the daily 8-fold one-hour
      interval 6% hypoxia that decreased manifestations of the anesthesia by 60-67%.
      The immunocytochemical light optical microscopy showed that in the brain cortex
      after the 8th seance of such hypoxia the number of neurons with the strong and
      moderate reaction to heat shock proteins (HSP-70) increased essentially, whereas
      the number of neurons with the weak reaction to these proteins decreased
      significantly. After the first hypoxia seances the number of cells with no
      reaction for the nuclear protein NeuN increased, while after its 8th seance the
      areas of the absence of neurons appeared. It is believed that one of the main
      causes of an increase of resistance of the rat organism to nitrogen anesthesia
      after seances of the many-day interval 6% hypoxia is accumulation of HSP-70 in
      brain motor cortex cells. At the same time, taking into account a possible cell
      death and areas of deletion of neurons in cortex at use of the hypoxic action, it
      is better to use as a preadaptogen the more moderate or not too frequent hypoxia.

PMID- 20799609
TI  - [Discrete phenotypical variability of electrophoretic specters of one of myogen
      systems in the Acipenseridae family].
AB  - Analysis of electrophoregrams of water-soluble proteins of white skeletal muscle
      of 10 fish species belonging to three genera of the Acipenseridae family has
      allowed revealing an earlier not described system that can serve as a biochemical
      marker. This protein system represents a set of five fractions (A, B, C, D, E). A
      part of the studied species is monomorphous for one of these fractions (sterlet,
      starred sturgeon, great sturgeon, and big shovelnose had phenotype A, barbel
      sturgeon--phenotype C, great Siberian sturgeon--phenotype D). In all individuals
      of the Amur sturgeon the identical three-component specter (phenotype ACE) was
      revealed. In the Sakhalin, Siberian, and Russian sturgeons a clearly expressed
      polymorphism was observed. Among the studied species the Russian sturgeon was
      characterized by the highest degree of heterogeneity and polymorphism. In the
      studied sample of this species all five protein variants are found, whereas in
      other species--only a part of this set.

PMID- 20799610
TI  - [Effect of chronic anosmia on morphofunctional parameters of the gustatory system
      primary centers of the carp Cyprinus carpio].
AB  - Morphofunctional state of neurons in primary centers of olfactory, external and
      intraoral gustatory systems in carp yearlings was studied at different time after
      bilateral anosming, with use of methods of morphometrical, biochemical, and
      histochemical analyses. The olfactory deafferentation produces centripetal
      translocation of olfactory bulbs and development of their degenerative changes.
      Chronic elimination of olfactory reception in carps leads to activation of
      neurons in the facial lobe of medulla--the primary center of the external
      gustatory system. The neuronal complexes of the vagus lobe representing the
      primary center of the intraoral taste did not have a similar reaction to
      elimination of the olfactory reception. The high level of central interaction of
      the fish olfactory and gustatory systems and its role in providing reliability of
      alimentary behavior are discussed.

PMID- 20799611
TI  - [In vivo studies of the main functional systems in the heteronemertean pilidium
      larva].
AB  - There is performed in vivo morphological study of the White Sea heteronemerteans
      belonging to the type of pilidium pyramidale (conussoidale). Based on the layer
      by-layer microshooting with subsequent computer processing, development of the
      pilidium digestive, nervous, and muscle systems is described from the stage
      following at once the gastrula to the premetamorphose larva. Peculiarities of
      structural organization of the main functional systems are revealed depending on
      the larva size and the stage of formation of imaginal discs. It is first shown
      that even in the not completely formed pilidium, neurons are located not only in
      integuments and wall of the digestive tract, but also in the depth of cupola
      along the central muscle retractor. Their processes are distributed between the
      main body parts and organs by seeming to perform connections of the apical organ
      and central muscle retractor with the digestive tract, blades, and the nerve
      plexus of the cupola wall. In the digestive tract between pharynx and stomach in
      the formed pilidium, the sphincter is first revealed. It has been shown that in
      the course of larva development, the non-orderly arranged and poorly developed
      muscle fibers gradually form in the blade the fan-like, whereas in the cupola
      wall, the net-like structure.

PMID- 20799612
TI  - [Peculiarities of ultrastructure of excretory system in Bothrioplana semperi
      (Platyhelminthes, Turbellaria)].
AB  - Ultrastructural study of morphology of cirtocytes and excretory channels was
      performed in the free living turbellaria Bothrioplana semperi (Turbellaria,
      Seriata). It has been shown that cirtocytes of this species are formed by two
      cells--the terminal and the proximal cells of the channel. The fan is composed of
      two rod rows. The external row goes out from the terminal cell, the internal one
      is a derivate of the channel proximal cell. Inside each rod of the external row
      there runs a bundle of microfilaments; it originates in the cytoplasm of the
      channel proximal cell distal to bases of the external rods. On the internal rod
      membranes there are noted small electrondense granules disposed separately or
      fused in the solid layer continuing into a dense "membrane" connecting rods of
      the external and internal rows. Rare internal leptotrichiae go out from the
      cirtocyte cavity bottom. External leptotrichiae are absent. The septate desmosome
      at the level of the terminal cell is absent, but is present in the channel
      proximal cell at the level of terminal of cilia. The apical surface of the
      channel cell carries rare short microvilli. The basement membrane of cells of
      excretory channels forms deep invaginations almost reaching the apical membrane.
      Epithelium of excretory channels is deprived of cilia. Ultrastructure of
      cirtocytes and excretory channels of B. semperi is similar to those in
      representatives of the suborder Proseriata (Seriata). The significance of
      ultrastructure of the Proseriata cirtocytes, especially of the order of formation
      of versh, for construction of phylogeny of Platyhelminthes is discussed.

PMID- 20799613
TI  - [Distribution of frataxin in eye retina of normal mice and of transgenic R7E mice
      with retinal degeneration].

PMID- 20799614
TI  - [Comparative analysis of rat survival under effect of acute heating and of
      poisons of animals belonging to different taxonomic groups].

PMID- 20799615
TI  - [About the olfactory system in the dragonfly of the Aeschna genus].

PMID- 20799616
TI  - [Organization of centromere regions of chromosomes in the lampbrush phase].
AB  - Centromeres have a pivotal role in the complex of structural elements that are
      required for precise segregation of eukaryotic chromosomes during two types of
      cellular divisions--mitosis and meiosis. Data of ultrastructural and
      cytomolecular analysis indicate significant changes in molecular composition and
      functional morphology of centromeres during preparation for the first meiotic
      division. The review is devoted to modern concepts of morpho-functional
      organization of chromosomal centromere regions in growing oocytes in birds and
      amphibians. Structure, molecular composition as well as domain organization of
      centromeres in the lampbrush phase are characterized; data of cytogenetic
      analysis are presented. Special attention is given to the significance and
      regulation of satellite DNA transcription in the nuclei of developing oocytes.
      Possible functions of centromere "protein bodies" formed at the primary
      constriction of meiotic bivalents are discussed.

PMID- 20799617
TI  - [Porosome: a new organelle and the universal secretion machine in cells].
AB  - A new cell organelle, porosome, discovered in the mid 1990's and its
      demonstration as the universal secretory machinery in cells is described. In
      contrast to the generally accepted belief that the secretory vesicle membrane is
      totally incorporated into the plasma membrane during cell secretion, it has been
      shown that secretory vesicles transiently dock and fuse with the porosome base
      via SNARE proteins to expel vesicular contents under intravesicular pressure
      which is generated by active transport of water through water channels located at
      the secretory vesicle membrane.

PMID- 20799618
TI  - [Gaba- and glycine-immunoreactive synapses in the spinal cord of the frog Rana
      temporaria].
AB  - Postembedding immunogold method was used to examine the distribution of gamma
      aminobutyric acid- and glycine-immunoreactives synapses on the motoneurons and
      primary afferent axons in frog spinal cord. Analysis of all labeled boutons on
      dendrites and somata of motoneurons showed that 7% were labeled for GABA, 23%
      only for glycine and approximately 70% were immunoreactive for both GABA and
      glycine. These results confirm the predominant role of glycine in postsynaptic
      inhibition of motoneuronal activity. Three populations of synaptic boutons were
      found on primary afferent axons: GABA-immunoreactive (25%), glycine
      immunoreactive (5%) and the majority of the immunoreactive synapses exhibited
      colocalization of two inhibitory transmitters. Greater proportion of axo-axonal
      synases was organized in synaptic triads. The possible roles of glycine in the
      axo-axonal synapses on the primary afferent fibers are discussed.

PMID- 20799619
TI  - [An extracellular pH changes registration by confocal microscopy in higher plant
      at the excitation potentials generation].
AB  - Confocal microscopy technique was applied for registration of apoplast pH changes
      in the Cucurbita pepo seedling stem during generation of action potential and
      variation potential. Fluorescent dye FITC-dextran was used for pH-changes
      registration. Analysis of fluorescence images and fluorescence spectra showed,
      that FITC-dextran was localized in cell walls. Propagation of action potential
      and variation potential was accompanied by transient increase of fluorescence
      intensity, which indicated alkalization of cell walls. This transient
      alkalization is proposed to be caused by a temporary inactivation of the H(+)
      pump in the plasma membrane.

PMID- 20799620
TI  - [N-acetylcysteine-induced reduction in susceptibility of transformed and
      embryonic cells to lytic activity of natural killer cells].
AB  - We studied N-acetylcysteine (NAC) ability to change the phenotype properties of
      several transformed and embryonic cells. We examined human epidermoid carcinoma
      A431 cells, murine hepatoma MH22a cells, and murine embryonic fibroblasts (MEFs)
      in terms of the sensitivity to natural killer (NK) recognition and abolishment.
      We have demonstrated that treatment with NAC (10 mM) results in a loss of
      susceptibility to NK cell activity by transformed A431 and MH22a cells similar to
      3T3-SV40 transformed cells whose partial reversion caused by NAC was revealed by
      us before. We have shown that MEFs are also sensitive to NK activity and
      abolished by NK cells as well as transformed cells. MEFs pretreated with 10 mM
      NAC as well as transformed cells lose their susceptibility to NK cell activity.
      The loss of cell sensitivity to NK cytolytic activity was accompanied by a
      reorganization of the actin cytoskeleton and the appearance of well-pronounced
      stress-fibers.

PMID- 20799621
TI  - [Changes in K+, Na+ and Cl- contents and K+ and Cl- fluxes during apoptosis of
      U937 cells by staurosporine. On the mechanism of cell dehydration in apoptosis].
AB  - K+, Na+ and Cl- balance and K+ (Rb+) and 36Cl fluxes in during apoptosis of U937
      cells caused by 0.2 or 1 microM staurosporine were studied by flame emission and
      radiotracer techniques. It is found that monovalent ion redistribution accounts
      for 2/3 of all decrease in the amount of intracellular osmolytes in apoptotic
      cells while 1/3 is due to the loss of other intracellular osmolytes. Na+ gain in
      apoptotic cells hampers dehydration is caused by K+ and Cl- loss. It is found
      that the rate of equilibration of 36Cl, Rb+ (K+) and 22Na+ between cells and the
      medium exceeds significantly the rate of alteration of cell ion content
      associated with apoptosis. It is concluded that apoptotic changes should be
      considered as a drift of the balanced ion distribution. Alteration of the ion
      balance in apoptosis, caused by 0.2 microM staurosporine, is associated with an
      increase in the uabain-resistant Rb+ (K+) "channel" influx and insignificant
      alteration of the uabain-sensitive "pump" influx. Stronger apoptosis, induced by
      1 microM staurosporine, is associated with a decrease in the pump fluxes and
      insignificant changes in the "channel" Rb+ (K+) fluxes. Decreasing of the Cl-
      level in apoptotic cells by a factor 1.4-1.8 is accompanied with a decrease in
      the flux, by a factor 1.2-1.6.

PMID- 20799622
TI  - [Computation of the K+, Na+ and Cl- fluxes through plasma membrane of animal cell
      with Na+/K+ pump, NKCC, NC cotransporters, and ionic channels with and without
      non-Goldman rectification in K+ channels. Norma and apoptosis].
AB  - The balance of K+, Na+ and Cl- fluxes through cell membrane with the Na+/K+ pump,
      ion channels and NKCC and NC cotransporters is considered. It is shown that all
      unidirectional K+, Na+ and Cl- fluxes through cell membrane, permeability
      coefficients of ion channels and membrane potential can be computed for balanced
      ion distribution between cell and the medium if K+, Na+ and Cl- concentration in
      cell water and three fluxes are known: total Cl- flux, total K+ influx and
      ouabain-inhibitable "pump" component of the K+ influx. Changes in the mortovalent
      ion balance in lymphoid cells U937 induced to apoptosis by 1 microM staurosporine
      are analyzed as an example. It is found that the apoptotic shift in ion and water
      balance in studied cells is caused by a decrease in the pump activity which is
      accompanied by a decrease in the integral permeability of Na+ channels without
      significant increase in K+ and Cl- channel permeabilities. Computation shows that
      only a small part of the total fluxes of K+, Na+ and Cl- accounts for the fluxes
      via NKCC and NC cotransporters. Therefore, cotransport fluxes can not be studied
      using inhibitors.

PMID- 20799623
TI  - [Spermatogenesis in Drosophila melanogaster: the role of the basic transport
      receptor of the mRNA (Dm NXF1)].
AB  - Specificity of regulation of genes expression at the transcriptional and
      posttranscriptional levels is typical for spermatogenesis in Drosophila and
      mammals, including humans. It becomes apparent in the existence of testis
      specific NXF (nuclear export factor). We have shown that the Dm NXF1 (SBR)
      protein is present in considerable amounts at all stages of the spermatogenesis.
      Using the antibody for the C-terminal part of the Dm NXF1 protein we have shown
      the cytoplasmic localization of the Dm NXF1 protein at early stages of the
      spermatogenesis. This protein is localized in the nuclear envelope at the stage
      of rounded spermatid. During the period of elongation, the Dm NXF1 protein has a
      polar localization, and is located only along one side of the extended spermatid
      nucleus. At the stage of spermatid individualization, this protein in the form of
      large cytoplasmic granules moves to the tail of the spermatozoon.

PMID- 20799624
TI  - [Comparative analysis of SGLT1 and GLUT2 transporter distribution in rat small
      intestine enterocytes and Caco2 cells during hexose absorption].
AB  - SGLT1 and GLUT2 hexose transporter distribution into enterocytes of small
      intestine isolated loop and Caco2 cell culture after absorption of high and low
      hexose concentrations has been considered. SGLT1 was found along intestine villus
      edge in isolated loop. After high concentration hexose load GLUT2 appeared to be
      situated in the apical parts of enterocytes. It is evident that GLUT2
      participates in hexose transport across apical membrane. Cultured Caco2 cells
      form microvilli and cell junction complex typical for enterocyte. Glucose and
      galactose absorption by the cells from incubation medium has been observed. SGLT1
      transporter is situated in the apical parts and around the nuclens of Caco2 cells
      and combined into globules. After low concentration hexose load, CLUT2
      transporter is localized in the basal parts of Caco2 cells. Caco2 cell culture
      can be used as a model for studying of hexose transport in small intestine
      epithelium.

PMID- 20799625
TI  - [Cellular factors of local protection under community acquired pneumonia].
AB  - The community acquired pneumonia (CAP) falls into the category of the most
      frequent human diseases and is one of the leading causes of death from infectious
      diseases. The main components that characterize the inflammatory process in the
      lungs at CAP include an increase in vascular permeability, and migration of
      neutrophils and monocytes/macrophages to the foci of infectious agents
      inoculation, and the reactivity of these cells defines the upshot of the disease.
      In the present work, a significant increase in the number of neutrophils and an
      increase in the number of perishing cells depending on the gravity of current CAP
      were determined. Herewith, the contents of necrotic neutrophils and macrophages
      in foci of inflammation dependent on the gravity of current CAP, while the
      difference between the factors of apoptosis in these patients was not reliable.
      Apoptotic cell death was mainly revealed in population of macrophages. Analysis
      of the phagocytic and enzymatic activities of cells of the local defense of CAP
      patients showed that the state of unspecific resistance of their organisms
      largely determined the severity of the disease and antibiotic treatment did not
      affect the normalization of neutrophils and macrophages functions.

PMID- 20799626
TI  - [Method of preparation of tissue engineering and cell cultivation collagen by
      acid extraction of calf skin].
AB  - Seven methods of preparation of intact native collagen with telopeptides by acid
      extraction of calf skin have been compared; the hide was first dehaired by
      original mild enzymatical method using Bacillus licheniformis protease. The
      noncollagenous proteins and proteoglycans were previously removed by different
      ways and collagen was extracted by acid solvents and purified by salt
      precipitation. The dynamic of noncollagen impurities removing was followed by
      noncollagen proteins and hexuronic acids analysis in extracts. The purity of the
      resulting collagen was determined by polyacrilamide gel electrophoresis. The gel
      forming capacity of the collagen was determined and the suitability of the
      product for tissue engineering was estimated by cultivation of fibroblasts and
      cardyomyocytes of new-born rats on collagen gells. All collagens obtained were
      not cytotoxic and had good gel-forming capacity. The preparation method with
      noncollagen impurities removing with 0.02 M K2HPO4 and collagen solution with 0.5
      M acetic acid and 5 mM EDTA proved to be the best by final yield of the product
      and cell reaction to it. Hence, the optimal variant of collagen preparation
      method has been developed. The Russian Federation patent on this method was taken
      out.

PMID- 20799627
TI  - [Valeology and biophysical medicine].
AB  - We analysed the official statistical data about the morbidity in different
      Ukrainian regions, its copulas over is brought with the ecological features in
      the environmental contamination of age-old features of development pathologies,
      which result in the loss of capacity and country's depopylation. Cited data about
      the medicinally conditioned diseases and by-reactions after drugs introduction.
      The own material contains the clinical supervisions results after additional
      application the instrumental oroterapy procedure--the drived gas environment with
      lowered oxygen partial pressure in co-operating with the traditional treatment
      for the patients suffering with the child's cerebral paralysis. The positive
      instrumental oroterapy effects was shown on the motive functions state,
      electroencephalography dates, about the main brain complex activity from 53
      childrens with pulsy. Drawn conclusion about the appropriateness of including the
      natural or instrumental oroterapy in the children's rehabilitation programs or
      for physiology regeneration in youth and adults.

PMID- 20799629
TI  - [The ways in which variations in space and atmospheric factors act upon the
      biosphere and humans].
AB  - The system analysis is validated to be an efficient means for studying the
      channels through which variations in space and tropospheric weather affect the
      biosphere (humans). The basics of the system analysis paradigm are presented. The
      causes of variations in space and tropospheric weather are determined, and the
      interrelations between them are demonstrated. The ways in which these variations
      affect the biosphere (humans) are discussed. Aperiodic and quasi-periodic
      disturbances in the physical fields that influence the biosphere (humans) are
      intercompared.

PMID- 20799628
TI  - Signal function of potassium channels--clinical aspects.
AB  - Potassium (K+) channels are the most diverse class of ion channels, and are
      important for regulating neuronal excitability and signaling activity in a
      variety of ways. They are major determinants of membrane excitability,
      influencing the resting potential of membranes, wave forms and frequencies of
      action potentials, and thresholds of excitation. Voltage-gated K+ cannels exist
      not as independent units merely responding to changes in transmembrane potential
      but as macromolecular complexes able to integrate a plethora of cellular signals
      that fine tune channel activities. There are a wide variety of therapeutic agents
      that are targeted to non-K+ channels, but result in unintended block of K+
      channels. This K+ channel block can result in potentially serious and sometimes
      even fatal side effects.

PMID- 20799630
TI  - [Correction of the bone tissue changes in the deficit of mechanical loading].
AB  - In a review the analysis of modern medical technologies of correction of the
      state of bone tissue is presented at situational hipokinezii, weightlessness or
      deficit of loading.

PMID- 20799631
TI  - [Relation of a suicidal behaviour with the heliogeophysical factors].
AB  - Heliogeophysical parameters of the environment at the time of realization of
      suicidal behaviours using the data of four independent cohorts from different
      Ukrainian regions, separately for men (totally 7585 cases) and women (totally
      4023 cases) for interval of 1989-2008 were analysed. A suicidal behaviour of men
      is actualized when geomagnetic activity decreases after its maximum.
      Heliogeophysical factors have smaller influence on women's suicidal behaviour.
      Suicide bombing attacks in Israel, Iraq and Afghanistan (for the period from 1994
      to 2008) tend to take place by the maximal values of geomagnetic activity or
      during changes in interplanetary magnetic field polarity from negative to
      positive. These findings promote future discussion regarding unifying
      psychological or psycho-physiological mechanisms in suicides and suicidal
      terroristic acts and have some predicting potential.

PMID- 20799632
TI  - [Influence of food restriction on the biomechanical properties of the tibia in
      male rats of different age].
AB  - The changes of tibial bones biomechanical properties after 28 daily 40% declines
      of calorie content of feed and subsequent period of proceeding in a food ration
      were study in young and adult rats.28 day diminishing of calorie content of day's
      ration decline of bone mass, load capacity, stiffness, energy of elastic
      deformation of tibial bones. The indexes of biomechanics properties of bones were
      normalized after 28 daily period of proceeding in the ordinary ration of feed.

PMID- 20799633
TI  - [Effects of hypokinesia and hypoxia on the bone static electrogenesis].
AB  - It was studied the conformities to law of quasistatic electric potential (QSEP)
      distribution on the periosteal surface of 64 adult Vistar rats-males fresh exited
      femur and their changes after dosed hypokinesia and hypoxia influences. The
      maximal negative sizes of QSEP were incorporated in epiphyseal-metaphyseal
      departments and minimal--in the central part of bone diaphysis. Conformities to
      law of QSEP distribution on the periosteal surface fresh exited bone represented
      the physiology unevenness of metabolic processes intensity in the different bone
      departments. Reparative regeneration was accompanied with strengthening of
      electro-negativity of reparations and adjacent parts and changing of physiology
      character of QSEP distribution on the periosteal surface of the damaged bone.
      Hypokinesia disturbed of bone static electrogenesis. It was accompanied with
      diminishing of QSEP size especially in bone parts which had hight level of
      metabolism. Dosed an intermittent normobarical and hypobarical hypoxia activated
      of bone static electrogenesis. More considerably increasing of QSEP in old rats
      was obtained after the intermittent hypobarical hypoxia influences.

PMID- 20799634
TI  - [Physiologic regeneration and functional activity of hepatocytes in normobaric
      hypoxia].
AB  - It was studied the effects of dosed normobaric hypoxia during 14 and 28 days on
      physiological regeneration and functional activity liver of parenhima fenomenas
      of adult rats. It was shown that after completion of experiment at rats increase
      sizes nucleus, the area of cytoplasm decrease, and also is increase the
      hepatocytes amount on tissue area unit. Concentration albumin increased after 14
      days ofnormobaric hypoxia. Activity alanine aminotranferease increased and
      aspartate aminotransferase activity decreased after 28 days of dosed normobaric
      hypoxia. Thus our study suggested that normobaric hypoxia stimulante
      morphological marcers functional action and regenerator liver ability.

PMID- 20799635
TI  - [The state of cyclic nucleotide system and morphofunctional changes of lung and
      heart tissues in hypoxia of different genesis].
AB  - It was investigated the intercommunication of the functional state of cyclic
      nucleotides (CN) system and morphofunctional states of lung and heart tissues and
      influence on these state of lipid peroxidation processes and adenylate cyclase
      system activity under development in organism of the hypoxic states of different
      genesis. Obtained dates testify that with the changes of cAMP and cGMP
      concentrations, and also with their ratio the level of hyperhydratation of air
      blood and blood-tissue barriers under the used influence on the organism are
      closely correlated. Intercommunication of the cyclic nucleotides system
      functioning and tissues oxygen consumption at the used influences carries
      sufficiently difficult and ambiguous character. It was shown that exactly at
      blood loss in lung and heart tissues there were the parallel diminishing of
      concentrations both cAMP and cGMP. It is accepted to correlate with a favorable
      histological dynamics. Exactly under these conditions the correlation of CN
      concentrations is possible to consider balanced and sent to limitation of
      displays of unfavorable influence of blood loss on investigated tissues
      ultrastructure. So, there is a tissue specific and depending from the type of
      influence on the organism character of intercommunication of the functional state
      of cyclic nucleotides system and morphofunctional states of lung and heart
      tissues.

PMID- 20799636
TI  - [Medical and technical aspects of using respiration monitoring of patients in
      clinical practice].
AB  - The article shows basic technical principles that have guided the design team
      ofpatient's respiration monitor. A block scheme of the monitor is showed, an
      algorithm of its work is described. Results of patient's respiratory function
      monitoring in postoperative period is discussed and illustrated by characteristic
      episodes of breathing. Authors describe the proposed method for analyzing the
      dynamics of respiration in time. Lot of possible steps for the improvement of
      hardware-software tools of patient's respiration monitor are determined.

PMID- 20799637
TI  - [Rheohepatography with ultrasound navigation of electrodes as biophysical method
      of the hepatic blood flow evaluation].
AB  - The transcutaneus Rheohepatography with ultrasound electrodes navigation (RUEN)
      discovered early specifically changes of hepatic blood flow in pts with diffuse
      hepatic pathology (DHP). It is necessary to use of the Conventional
      Rheohepatography for screening hepatics hemodynamics disorders in pts with DHP.
      For more differentiated approach it is necessary to use Doppler imaging of the
      hepatic blood flow. It is necessary to use the ultrasound electrodes navigation
      for increase of the self-descriptiveness Rheohepatography and for inclusion ofa
      maximum quantity hepatic parenchyma between interelectrodes space. As against the
      classical analysis extremities rheography in interpretation RUEN it is necessary
      to take into account, that the liver has 2 ways of inflow (proper hepatic artery
      and portal vein) and 1 way of outflow (hepatic veins running to cava inferior
      vein).

PMID- 20799638
TI  - [Mental foramens and dolphin hearing].
AB  - Detection thresholds of short broadband acoustic impulses with an energy maximum
      on frequencies 8, 16, 30 and 100 kHz was measured in the dolphin (Tursiops
      truncatus p.) with using techniques of behavioral responses in the indoor pool.
      At acoustic shielding of mental foramens, detection thresholds of these impulses
      worsen on 30, 34, 40 and 50 dB, respectively. The new original results obtained
      experimentally prove that mental foramens are the unique sound-conducting pathway
      for sounds of about 6-160 kHz frequency band (in consideration of stimulus
      broadbandness). In this connection the assumption that morphological structures
      of the lower jaw represent a specialized peripheral part of the dolphin hearing,
      which was based on studying of morphology and results of modelling, receives
      additional experimental confirmation. The mental foramens play part of external
      auditory canals and conduct all frequency range of the hearing of dolphin into
      fat body of the mandibular canal. Via fat body sounds transmit to a lateral side
      of an acoustical bone and into the middle and inner ear. From morphology
      similarity, it is possible to assume presence of the similar sound-conducting
      mechanism in Odontoceti.

PMID- 20799639
TI  - [In vitro organotypic cultivation of adult newt and rat retinas].
AB  - Adult rat and newt retinas were studied during long organotypic 3D cultivation. A
      high proliferation level was discovered in the region of growth by applying DNA
      synthesis markers and in vitro mitosis registration in newt retina. Aggregates
      were formed in the retina spheroid cavity because dedifferentiated cells migrated
      into this region. Small cell populations in nuclear layers also had dividing and
      migration capacity. Rosette formation has been shown in newt retina. It is a
      characteristic of fetal retinal development under pathological conditions. The
      antiG FAP antibody dye demonstrated an increase in the parent M@uller cell
      population and generation of a small cell pool with short GFAP-extensions de
      novo. Recoverin expression studies detected its translocation from photoreceptor
      extensions to the cell bodies. Moreover, protein was presented in some cells
      inside the spheroid. It has been shown for the first time that cell proliferation
      occurred in the developing adult rat retinal spheroid in vitro; BrdU-positive
      cells and multiple mitoses were revealed in this zone. However, the source of
      proliferation was not in the peripheral retina, and stable macrophages and glial
      cells located among neurons of the inner nuclear layer had the ability to divide.
      The antiGFAP antibody showed an increase in GFAP fibers in the rat retina as well
      as in the newt retina. Recoverin translocated into photoreceptor perikaryons and
      the outer plexiform layer in cultivated rat retina. Interestingly, some cells
      with probably de novo expression of recoverin were discovered in rat and newt
      retinas.

PMID- 20799640
TI  - [Wound healing potential of chitosan and its N-sulfosuccinoyl derivatives].
AB  - Comparative study of chitosan wound healing properties and its synthesized
      derivatives in MC-100 gel was carried out using the model of experimental full
      thickness skin wounds. It was determined that N-sulfosuccinoyl chitosan
      derivatives added into the gel in a concentration of 0.05% possess the higher
      wound healing activity in comparison with other chitosan derivatives and decrease
      the half-healing period of wounds 2-3 times in comparison with the control.

PMID- 20799641
TI  - [The drug hypoxen--a new inhibitor of mitochondrial respiration and mitochondrial
      dehydrogenases].
AB  - The effect of hypoxen on the oxygen consumption and activity of dehydrogenases in
      rat liver mitochondria has been studied. The addition of hypoxen to mitochondria
      caused a speed reduction of phosphorylating and uncoupling respiration. The
      minimal effective concentration of hypoxen was 15 microg/ml with succinate, 60
      microg/ml with pyruvate or palmitoylcarnitine, and 120 microg/ml with glutamate
      as the substrates. The activities of malate, glutamate, and succinate
      dehydrogenases in mitochondria were significantly decreased by the effect of
      hypoxen.

PMID- 20799642
TI  - [Chromosomal mutations in Scotch pine (Pinus sylvestris L.) growing in a
      hydromorphic environment: a first case of a giant chromosome detection].
AB  - Chromosomal mutations and mixoploidy have been revealed in the seedlings of
      Scotch pine (Pinus sylvestris) growing in a hydromorphic environment. A giant
      chromosome was detected for the first time in gymnosperms.

PMID- 20799643
TI  - [Testate amoebae inhabiting middle taiga bogs in Western Siberia].
AB  - The population of testate amoebae from the most typical middle taiga bogs of
      Western Siberia have been studied. More than one hundred (103) species and
      intraspecific taxons of testate amoebae have been revealed in recent surface
      samples. The relation between ecological characteristics of habitats and the
      composition of a Protozoa population has been demonstrated. The ecological
      preferences of species concerning the index of wetness, ash level, and acidity
      have been revealed. Using the correspondence analysis, the ecological optimums
      and the tolerance of species and intraspecific taxons of testate amoebae have
      been established.

PMID- 20799644
TI  - [Temporal dynamics of genetic diversity of Japanese scallop Mizuhopecten
      yessoensis (Jay, 1856)].
AB  - The season and age-related dependence of the distribution of the frequency of
      alleles and of five polymorphous loci have been studied for eight cultivated
      samples of the Japanese scallop M. yessoensis (Jay) from Alexeev Bay (Popov
      Island, Sea of Japan) using polyacrylamide gel electrophoresis. The consistency
      of the frequency of alleles and of heterozygotes was revealed for samples with an
      age greater than one year independently of the season and age. Samples of the
      younger (11 months) mollusks can have reliable deviations of the frequency of
      allele and of heterozygotes. However, as the sample reaches a certain age, these
      genetic parameters correspond to values general to the whole population. The
      episodic influence of ecological factors on the younger age groups of mollusks is
      discussed.

PMID- 20799645
TI  - [Termites (Isoptera) in forest ecosystems of Cat Tien National Park (Southern
      Vietnam)].
AB  - The species composition and termite community populations were studied and the
      total land termites biomass was estimated in five forest habitats of Cat Tien
      National Park, Southern Vietnam. Twenty-four species of two families,
      Rhinotermitidae (1 species) and Termitidae (23 species), the predominant
      representatives of the subfamily Macrotermitinae, were found in mounds and in
      soil samples. On the test plots the density of termite mounds averaged 68 per
      hectare, primarily the mounds of three Macrotermes species. Destructive sampling
      allowed estimation of the caste composition and total community biomass based on
      six termite mounds of the prevailing species (Globitermes sulphureus,
      Microcerotermes burmanicus, Macrotermes carbonarius, M. gilvus, M. malaccensis,
      and Hypotermes obscuriceps). The total number of termites in the nests ranged
      from 65 000 to 3 150 000 individuals with the total biomass ranging from 185 to
      2440 g live weight. The total abundance of nesting Macrotermes species alone
      could conservatively be estimated as 2.5 million individuals and 20.5 kg live
      weight per hectare. The number of soil- and litter-feeding termites averaged for
      the test plots was estimated at about 60 ind./m2. Four species dominating on the
      test plots (M. carbonarius, M. gilvus, M. malaccensis, and H. obscuriceps) belong
      to active tree litter feeders.

PMID- 20799646
TI  - [Mechanisms of the hypothalamic-pituitary and immune system regulation: the role
      of gonadotropin-releasing hormone and immune mediators].
AB  - Different aspects of the reciprocal regulatory influence of systems producing the
      immune and gonadotropin-releasing hormone (GnRH) in pre- and postnatal ontogeny
      are discussed in this review. GnRH is a neurohormone synthesized by a small
      population of neurons located in the anterior hypothalamus, which regulates the
      secretion of gonadotropines in the anterior lobe of the pituitary gland and they
      finally regulate the synthesis of sex steroids. Particular attention is given to
      analysis of the data involving the role of thymus peptides and cytokines in GnRH
      system regulation in the normal condition and in the case of inflammation
      development caused by endotoxines in adult animals. The main prospects of the
      studies involving the influence of proinflammatory cytokines on GnRH-neuron
      migration and differentiation in prenatal ontogenesis are also discussed.

PMID- 20799647
TI  - [Protective antithrombotic effects of proline-containing peptides in the animal
      body subjected to stress].
AB  - We discovered that simple proline-containing peptides Gly-Pro, Pro-Gly, Pro-Gly
      Pro, and semax had an antistress protective effect on the organism appearing as
      anticoagulation system activation. Repeated intranasal injection of each of these
      peptides to rats prior to acute immobilization stress prevented a
      hypercoagulation response to prolonged stress lasting 60 min. At the same time
      there was increase of antithrombotic, anticoagulant, and fibrin depolymerization
      activity and recovery of enzymatic fibrinolytic activity. Dipeptides were found
      to have the greatest antistress effect. Our results showed that semax had a
      protective effect against enhanced blood coagulability resulting from repeated
      immobilization stress.

PMID- 20799648
TI  - [Influence of ionizing radiation on the formation of adult antennae in large
      fruit-tree tortrix Archips podana Scop. (Lepidoptera, Tortricidae)].
AB  - The influence of sterilizing doses of X-radiation on the formation of adult
      antennae during the pupa period of development of Archips podana was studied. We
      found a change in the number of coeloconic and auriculate sensilla in those imago
      whose pupae were exposed to radiation. A slow-down in the process of antennae
      formation at the pupal stage was registered after the irradiation of instar five
      larvae and newly formed pupae.

PMID- 20799649
TI  - [Nanoparticles in the environment and their effect on hydrobionts].
AB  - This paper summarizes the data on the effect of engineered nanoparticles on
      aquatic organisms. The issues of penetration and accumulation of nanoparticles in
      the body of hydrobionts and their toxic effect, biotransformation, and migration
      along food chains are considered. It is demonstrated that the behavior of
      nanomaterials in the environment and their effect on living organisms have been
      studied insufficiently and require close attention, because their release into
      the environment will increase in the very near future.

PMID- 20799650
TI  - [Intraspecific variability of life strategies in boreal fishes inhabiting wide
      ranges].
AB  - Variability of the population structure, parameters of growth, and reproduction
      were analyzed in two freshwater (Siberian sturgeon and bream) and two marine (cod
      and flounder) widespread boreal fish species. These species have similar
      spectrums of adaptive life strategies including (a) the strategy of populations
      inhabiting zones of the species optimum, (b) the strategy of populations
      inhabiting the northern peripheral zones of low temperature and unstable food
      supply, (c) the strategy of populations inhabiting the southern peripheral zones,
      and (d) the strategy of dwarf forms. These spectrums of life strategies are
      apparently determined by (1) a high degree of intraspecific variability of the
      protein synthesis scale within extensive ranges of the species under study, (2)
      labile mechanisms regulating the plastic and generative metabolism ratio during
      ontogeny which are determined not only by thermal conditions but also by the
      level of food supply and its fluctuations, and (3) the mechanism regulating the
      size and weight of eggs.

PMID- 20799651
TI  - [Organic substances in the artificial forest ecosystems created on overburden
      dumps of open-cut coal mines in Middle Siberia].
AB  - The stock and structure of organic substances in the pine tree plantations on the
      overburden dumps of open-cut coal mines in Middle Siberia have been determined.
      It has been shown that the forming forest biogeocenoses differ from the natural
      phytocenoses and soils of the forest landscapes in the structure of the carbon
      pool and its distribution between the vegetation and soil components. In
      artificial forest ecosystems, the bulk of the plant component is accumulated in
      the aboveground part of the forest stand (40-59%). The aboveground grass cover
      contains only 0.1-1.4% of the total phytomass stock of the ecosystem. The annual
      accumulation of organic substances in the initial soils amounts to 0.28-1.45
      t/ha.

PMID- 20799652
TI  - [Space radiation doses in the anthropomorphous phantom in space experiment
      "Matryeshka-R" and spacesuit "Orlan-M" during extravehicular activity].
AB  - Russian space experiment "Matryeshka-R" was conducted in 2004-2005 to study dose
      distribution in the body of anthropomorphous phantom inserted in a spacesuit
      imitating container mounted on outer surface of the ISS Service module
      (experiment "Matryeshka"). The objective was to compare doses inside the phantom
      in the container to human body donned in spacesuit "Orlan-M" during
      extravehicular activity (EVA). The shielding function was calculated using the
      geometric model, specification of the phantom shielded by the container, "Orlan
      M" description, and results of ground-based estimation of shielding effectiveness
      by gamma-raying. Doses were calculated from the dose attenuation curves obtained
      for galactic cosmic rays, and the AE-8/AP-8 models of electron and proton flows
      in Earth's radiation belt. Calculated ratios of equivalent doses in
      representative points of the body critical organs to analogous doses in phantom
      "Matryeshka" H(ORLAN-M)/H(Matryeshka) for identical radiation conditions vary
      with organs and solar activity in the range from 0.1 to 1.8 with organs and solar
      activity. These observations should be taken into account when applying
      Matryeshka data to the EVA conditions.

PMID- 20799653
TI  - [Radiation sterilization of units of a Mars descent module--a miniature
      meteorological station].
AB  - Subject of the test was a procedure of electron sterilization of Mars descent
      module units. As a result, data on distribution of absorbed dose field across the
      surface and by the entire volume of the mockup of a miniature meteorological
      station (MMS) were obtained In addition, electron sterilization technology was
      developed and the range of absorbed dose from electron radiation that will
      sterilize reliably packaged MMS hardware were defined in the interval from 30 to
      40 kGy.

PMID- 20799654
TI  - [Investigation of cardiovascular adaptation to postural passive test in the
      course of selecting candidates for special contingent].
AB  - Selection of candidates for special contingent is made with the focus on
      evaluation of cardiovascular functioning and adaptability to stresses, and
      detection of pre-disease shifts in CV regulation. Hemodynamics regulation was
      assessed by tilt testing of 15 essentially healthy men at the age of 18 to 34.
      The tilt table was initially at 0 degrees (baseline), turned at +75 degrees (20
      min), and then back to 0 degrees for 5-min recovery. Simultaneously with the
      standard measurements of ECG and blood pressure, the myocardium state was
      registered with the use of KardioVizor-06; cerebral circulation was evaluated
      using rheoencephalography and microcirculation vessels, -ultrasonic Doppler.
      Three human subjects exhibited hypotensive reactions to the tilt test and two
      showed hypertensive reactions. However, no changes were present on ECG records.
      Hence, in-depth investigation of the CV reaction to tilt test is capable to
      reveal incipient regulatory disorders and their trend, and to assess adaptability
      to stresses.

PMID- 20799655
TI  - [Criteria of noise pathologies in aviation specialists and their prognostic
      implications].
AB  - The paper outlines the criteria of noise pathologies in aviation specialists
      after extended period of exposure to high-intensity noise and infrared sound.
      Analysis of morbidity and clinical researches shows prevalence of such
      pathologies as neurosensory deafness, hypertension and discirculatory
      encephalopathy. These disorders were correlated with career length.

PMID- 20799656
TI  - [Biochemical profile of human-spacesuit interaction].
AB  - The article discusses and analyzes the issues of optimizing energy, kinematic and
      dynamic structures of the process of human-spacesuit system movement.
      Recommendations concerning system stabilization during posture acquisition and
      motion are made; the biomechanic requirement for spacesuit R&D is that joints
      with preset frequencies must be designed.

PMID- 20799657
TI  - [Morphofunctional state of hepatocytes nuclear apparatus in Mongolian herbils
      after the flight on space apparatus Foton-M3].
AB  - Morphofunctional state of hepatocytes nuclear apparatus was analyzed in the liver
      of Mongolian gerbils Meriones unguiculatus returned from 12-d space flight of
      Foton-M3 (SF) and their vivarium and ground synchronous controls. Volume, ploidy
      and number of hepatocyte nuclei, nucleolus dimensions and number as well as
      contacts with karyolemma were determined in the central, intermediate and
      peripheral areas of the liver classical lobe. Also, total number of mitoses and
      amitoses was determined in the liver parenchyma. The vivarium control animals
      displayed specifics of the nucleus apparatus structure that depended on intralobe
      topography. Based on the selected criteria, high functional activity was
      characteristic of cells in the intermediate area. According to the criteria,
      nuclear apparatus in the synchronous control tended to down the functional
      activity The adaptive adjustment of nuclei in SF seemed to have been initiated by
      changes in the hepatic blood flow: volumes of hepatocyte nuclei and nucleoli
      increased as did the number of nuclei in cell, whereas ploidy made a decrease,
      especially in the intermediate area. Under the SF conditions, particularly
      important compensatory mechanism for the liver function was intensification of
      amitosis and consequent increase of the population of dinuclear hepatocytes.

PMID- 20799658
TI  - [Electrogenic activity of Na-K-ATPase and calcium ions in m. soleus fibers of
      rats and Mongolian gerbil during simulation of gravitational unloading].
AB  - Some of the electrophysiological parameters of m. soleus of rat and Mongolian
      gerbil, and Ca ions content in fiber myoplasm were compared in different periods
      of gravitational unloading simulated by tail-suspension. No difference was found
      between the control animals as for membrane potential at rest, electrogenic
      activities of Na-K-ATPase and its isoforms, and input resistance of m. soleus
      fibers. At the same time, unlike rats, gerbils exhibited a substantial Ca
      decrease in myoplasm. From day one to 14 of gravitational unloading the pace of
      electrophysiological changes in gerbil's m. soleus was noticeably slower than of
      rat's, whereas Ca ions depositing in myoplasm was observed in both species
      already at the beginning ofsuspension. Analysis of the results suggests that
      adaptive changes in m. soleus of Mongolian gerbil and rat during simulated
      gravitational unloading are fundamentally different due to, probably, peculiar
      water-electrolyte metabolism, type of locomotion, and other factors which are
      still unclear.

PMID- 20799660
TI  - [Effect of mechanic stimulation of foot support zones during 7-day dry immersion
      on alterations of ocular saccades kinematics associated with immersion].
AB  - Purpose of the investigation was to evaluate how daily sessions of mechanic
      stimulation (MS) of foot support zones applied to mitigate the effects of lack of
      support loading on the postural muscles influence ocular saccades during
      prolonged support deprivation. According to the experimental protocol, before and
      immediately after 7-day dry immersion, 4 control and 4 MC human subjects
      (experimental group) implemented the test of rapid blanking light target
      appearing on the visual field periphery. Eye motions were detected using infrared
      images obtained at 200 Hz. Analysis of normalized and consolidated data showed
      that MC of foot support zones moderated significantly alterations in ocular
      saccade kinematics associated with support load deprivation confirmed by
      recruitment of support afferentation in sensory input to mechanisms of ocular
      saccade generation.

PMID- 20799659
TI  - [Effect of vibrostimulation on support zones of rat's feet, and support loading
      on titin N2A-isoform and T2-fragment in m. soleus under the conditions of
      simulated microgravity].
AB  - Effects of daily 3-hr vibrostimulation of foot support zone and 3 hrs. of usual
      locomotion on titin N2A-isoform and proteolytic T2-fragment were studied in m.
      soleus of rats during 7-d suspension. Besides, effects of single one-hour support
      loading following 7-d weight-deprivation on titin N2A- and T2-forms were also
      evaluated in the muscle. Relative N2A content in m. soleus of the suspended group
      was noted to reduce approximately 25% as compared with the group of control. In
      the meantime, relative T2 content grew 2-3 times. Along with other changes in the
      muscle apparatus, N2A reduction contributes to the decline of m. soleus
      contractility in suspended rats, and development of the "hypogravity muscular
      syndrome" The daily 3-hr vibrostimulation of the foot support zones substantially
      (almost twice) decreased N2A disintegration with parallel reduction in
      approximately 1.5 times relative T2 content comparing with the Suspension group.
      Three hours of locomotion a day during suspension did not appear to decrease the
      relative N2A content in m. soleus. However, in this group of animals the relative
      T2 content in m. soleus was twice as high as in the control. Single-time
      presentation of support load for one hour soon after 7-d suspension resulted in
      more significant (approximately 30%) reduction in relative N2A content and
      twofold fall of relative T2 content as compared with m. soleus of the rats in
      group Suspension. These data attest to the leading role of support stimulation in
      maintaining the structural and functional properties of the musculoskeletal
      system, specifically the titin N2A-isoform content in m. soleus of rat deprived
      of gravitational loading. Besides, it was also shown that tracking changes in
      titin makes possible to follow the course of hypogravitational muscle syndrome
      and to evaluate effectiveness of preventive methods.

PMID- 20799661
TI  - [Effects of different neuromediators and regulatory peptides on the impulse
      activity of neurons in vestibular zone-I of the cerebral cortex].
AB  - Microelectrodes and micro-iontophoresis of physiologically active substances in
      experiments with cats immobilized by muscle relaxants made it apparent that
      different classical neuromediators (acetylcholine, norepinephrine, GABA and
      others) and regulatory peptides (enkephalins, thyrotropin-releasing hormone,
      vasoactive intestinal peptide (VIP), somatostatin (SS) and others) are capable to
      influence directly 68 to 100% of neurons in vestibular zone-I of the cerebral
      cortex. In the presence of L-glutamate, the inhibiting effect of enkephalins, VIP
      and SS on the neurons impulse activity was essentially unaltered. Also it was
      shown that enkephalins, VIP and SS are potent to augment the inhibiting effect of
      GABA and glycine. Therefore, these substances may have the neuromediator and/or
      neuromodulator role in this cortical zone.

PMID- 20799662
TI  - [Solar phase effect on elasticity of the brachial artery and blood flow in
      humans].
AB  - Single and double examinations of normal males and females in the course of 11
      year solar cycle with the use of oscillovasometry and occlusive plethysmography
      established a direct correlation between the effective diastolic radius of the
      brachial artery and solar activity characteristics on the day of examination,
      i.e. number of solar spots and intensity of radiation with the 10.7 cm
      wavelength. Other blood flow parameters demonstrated opposite correlations with
      the factors in males and females. As solar activity increased, females displayed
      linear decrements of arterial elasticity and regional peripheral resistance and
      growth of the volumetric blood flow velocity equally at rest and at the peak of
      post-occlusion reactive hyperemia. In males, the correlations had the reversed
      sign. Besides, males were noted to reduce venous reserve and venous outflow from
      antebrachial muscles proportionally to the increase of Wolf number. It is
      inferred that elevated solar activity may be responsible for impairment of the
      feeling of well-being of people with reduced cardiovascular reserve, particularly
      in space tight or at high altitudes in the absence of or under weak protection of
      the geomagnetic field and ozone layer.

PMID- 20799663
TI  - [Polyphase character of the dependence of Brassica napus germ root and hypocotyl
      growth on zeatin and thidiazuron concentrations with view of applicability to
      biological life support systems].
AB  - Physiologically active substances are considered as a potential component of
      plant cultivation technologies for biological life support systems. In
      spacelight, plant reactions to growth-regulating agents may be changed by the
      specific stress factors such as microgravity, radiation, and trace admixtures in
      cabin air. Complex character of the concentration dependence of PAS efficiency
      and consequent variability generate a need to optimize plant growth regulating
      technologies in order to stabilize the wanted effect. Pattern of the
      concentration dependence of zeatin and tidiazurone effects on roots and
      hypocotyls growth was analyzed in rape germs. 24-hour Brassica napus germs grown
      in the dark in thermostat at 24 degrees C were transferred to Petri dishes with
      solutions of cytokinins under study for continued incubation under the same
      conditions for the next 24 hours. Roots and hypocotyls were measured. Zeatin
      concentration curve for roots was multiphase and, in addition to the general
      trend towards greater inhibition with increase of phyto-hormone concentration and
      had clearly defined minimum and maximum. The dependence of root growth inhibition
      on tidiazurone concentration also was not monotonic and had a distinct similarity
      with the zeatin curve. Gradual increase of tidiazurone concentration used in
      combination with zeatin brought about a predictable gradual twist of the zeatin
      curve; however, in most of the instances no additive cytokinin effect was
      observed. A supposition can be made that PAS interaction with the phytohormone
      regulation system may be a factor in variability of activity of these substances.

PMID- 20799664
TI  - [Multipurpose probe for underwater assessment of marine basin ecology].
AB  - [The multipurpose probe for real-time assessment of behavior reactions of marine
      mammals and concurrent temperature and noise pollution measurements was subjected
      to field testing]

PMID- 20799665
TI  - [Radioprotective effect of "light" water: doubtful validity].
AB  - Several publications have reported a radioprotective and immunopotentiating
      action of "light" water with low content of such stable isotopes as deuterium and
      18O. Validity of these statements is the subject of the Letter to editors.
      Investigations of "light" water compare with that of water purified of a
      microelement. Prolonged consumption of this water may result in deficiency of the
      microelement, whereas the positive effect of absence in water of a natural
      microcomponent is impossible or very unlikely.

PMID- 20799666
TI  - Evidence based practice in CLS education.

PMID- 20799667
TI  - Earner-carer model at the crossroads: reforms and outcomes of Sweden's family
      policy in comparative perspective.
AB  - Following the 2006 election, the Swedish earner-carer model of family policy
      seems to have come to an important crossroads, and questions have been raised
      about the future course of policies. Will the prototypical earner-carer model in
      Sweden persist? The separate reforms in cash transfers, services, and tax systems
      in several respects seem to point in contradictory directions, simultaneously
      introducing new principles of social care. In this article, past and present
      reforms and potential outcomes of policies are discussed from an institutional
      and comparative perspective. Reviewing research on outcomes of earner-carer
      policies for gendered patterns of productive and reproductive work, class-based
      stratification, child well-being, fertility, and work-family conflict, the
      article also contributes to the discussion about future challenges for family
      policy institutions in Sweden and other advanced welfare states.

PMID- 20799668
TI  - Welfare state regime life courses: the development of western European welfare
      state regimes and age-related patterns of educational inequalities in self
      reported health.
AB  - This article uses data from three waves of the European Social Survey (2002,
      2004, 2006) to compare educational inequalities in self-reported health (good vs.
      bad) and limiting longstanding illness in six age groups based on decade of birth
      (1930s-1980s) in 17 countries, categorized into four welfare state regimes (Anglo
      Saxon, Bismarckian, Scandinavian, Southern). The authors hypothesized that health
      inequalities in these age groups would vary because of their different welfare
      state experiences-welfare state regime life courses-both temporally, in terms of
      different phases of welfare state development (inequalities smaller among older
      people), and spatially, in terms of welfare state regime type (inequalities
      smaller among older Scandinavians). The findings are that inequalities in health
      tended to increase, not decrease, with age. Similarly, inequalities in health
      were not smallest in the Scandinavian regime or among the older Scandinavian
      cohorts. In keeping with the rest of the literature, the Bismarckian and Southern
      regimes had smaller educational inequalities in health. Longitudinal analysis
      that integrates wider public health factors or makes smaller comparisons may be a
      more productive way of analyzing cross-national variations in health inequalities
      and their relationship to welfare state life courses.

PMID- 20799669
TI  - Trade policy, health, and corporate influence: British American tobacco and
      China's accession to the World Trade Organization.
AB  - Tobacco market liberalization can have a profound impact on health. This article
      analyzes internal documents of British American Tobacco (BAT), released as a
      result of litigation in the United States, in order to examine the company's
      attempts to influence negotiations over China's accession to the World Trade
      Organization. The documents demonstrate that BAT attempted to influence these
      negotiations through a range of mechanisms, including personal access of BAT
      employees and lobbyists to policymakers; employment of former civil servants from
      key U.K. government departments; use of organized business groups such as the
      Multinational Chairmen's Group and the European Round Table; and participation
      and leadership in forums organized by Chatham House. These processes contributed
      to significant concessions on the liberalization of the tobacco market in China,
      although the failure to break the Chinese state monopoly over the manufacture and
      distribution of cigarettes has ensured that foreign tobacco companies' share of
      the Chinese market has remained small. World Trade Organization accession has
      nevertheless led to a profound restructuring of the Chinese tobacco industry in
      anticipation of foreign competition, which may result in more market-based and
      internationally oriented Chinese tobacco firms.

PMID- 20799670
TI  - "Medical tourism" and the global marketplace in health services: U.S. patients,
      international hospitals, and the search for affordable health care.
AB  - Health services are now advertised in a global marketplace. Hip and knee
      replacements, ophthalmologic procedures, cosmetic surgery, cardiac care, organ
      transplants, and stem cell injections are all available for purchase in the
      global health services marketplace. "Medical tourism" companies market "sun and
      surgery" packages and arrange care at international hospitals in Costa Rica,
      India, Mexico, Singapore, Thailand, and other destination nations. Just as
      automobile manufacturing and textile production moved outside the United States,
      American patients are "offshoring" themselves to facilities that use low labor
      costs to gain competitive advantage in the marketplace. Proponents of medical
      tourism argue that a global market in health services will promote consumer
      choice, foster competition among hospitals, and enable customers to purchase high
      quality care at medical facilities around the world. Skeptics raise concerns
      about quality of care and patient safety, information disclosure to patients,
      legal redress when patients are harmed while receiving care at international
      hospitals, and harms to public health care systems in destination nations. The
      emergence of a global market in health services will have profound consequences
      for health insurance, delivery of health services, patient-physician
      relationships, publicly funded health care, and the spread of medical
      consumerism.

PMID- 20799671
TI  - A European perspective on medical tourism: the need for a knowledge base.
AB  - Since the early 1990s, medical tourism, whereby individuals choose to travel
      across national borders or overseas to receive treatments, has been increasingly
      recognized in the United States and Asia. This article highlights the emergence
      of medical tourism in the European context. It examines the drivers for such
      developments and situates medical tourism within the broader context of health
      globalization and forms of patient mobility in the European Union. In outlining
      the developments of medical tourism in Europe, the authors distinguish between
      two types of medical tourist: the citizen and the consumer. The discussion
      explores the need for greater empirical research on medical tourism in Europe and
      argues that such research will contribute toward knowledge of patient mobility
      and the broader theorization of medical tourism. The authors make suggestions
      about the content of this research agenda, including understanding the
      development of medical tourist markets, the nature of choice, equity
      implications, the role of brokers and intermediaries, and general issues for
      health management.

PMID- 20799672
TI  - The good, the bad, and the ugly of partnered research: revisiting the
      sequestration thesis and the role of universities in promoting social justice.
AB  - As universities increasingly rely on external sources of research funding,
      researchers worldwide are realizing that if their work is financially supported
      by organizations with distinct political or financial interests, they risk their
      careers if their results deviate from the interests of their funding partners.
      This article presents a case that illustrates how ugly this situation can become.
      Reviewing the literature on the advantages and dangers of partnered research, the
      historical role of universities, funding trends, and university mission
      statements, the authors contend that universities must engage in service learning
      and participatory action research, but must ensure that faculty members engaging
      in academic activity with partners-whether industry, hospitals, governments,
      nongovernmental organizations, or communities-have their professional integrity
      protected. If doubt exists about whether the partner can or will honor these
      principles or the mission of universities for social good, universities should
      avoid granting joint or affiliate appointments or accepting funds or favors of
      any kind. Universities also need formal structures to ensure ethical application
      of innovation and principled partnership engagement. In becoming servants of
      government or corporatism, universities have become less vital to society and are
      failing in their mission to promote social justice and sustainability. Strong
      measures are needed to restore public trust.

PMID- 20799673
TI  - Only half the problem is being addressed: underinsurance is as big a problem as
      uninsurance.
AB  - This article examines the sociodemographic and health characteristics of the
      underinsured-people who have some health insurance but are having trouble paying
      for health care or medications. It uses data from the Boston Area Community
      Health (BACH) Survey, a large (N=5503) community-based random sample of Boston
      residents aged 30 to 79 years (1767 black, 1,877 Hispanic, and 1859 white; 2301
      men and 3202 women). The authors found that minorities were less likely than
      whites to have health insurance (for men and women, respectively, 30% and 19% of
      Hispanics, 16% and 9% of blacks, and 9% and 7% of whites lacked health
      insurance). Blacks were the most likely to be underinsured (for men and women,
      respectively, 18% and 20% of blacks vs. 9% and 14% of Hispanics and 8% and 12% of
      whites were underinsured). Those of lower and middle socioeconomic status were
      also more likely to be uninsured or underinsured. The health status of the
      uninsured was similar to that of the adequately insured, whereas those who were
      underinsured reported more co-morbidities and depression. The underinsured are
      generally older and sicker, and make greater use of the health care system, and
      may present a larger public health and health policy challenge than the
      uninsured.

PMID- 20799674
TI  - Social class inequalities in the utilization of health care and preventive
      services in Spain, a country with a national health system.
AB  - In Spain, despite the existence of a National Health System (NHS), the
      utilization of some curative health services is related to social class. This
      study assesses (1) whether these inequalities are also observed for preventive
      health services and (2) the role of additional private health insurance for
      people of advantaged social classes. Using data from the Spanish National Health
      Survey of 2006, the authors analyze the relationships between social class and
      use of health services by means of Poisson regression models with robust
      variance, controlling for self-assessed health. Similar analyses were performed
      for waiting times for visits to a general practitioner (GP) and specialist. After
      controlling for self-perceived health, men and women from social classes IV-V had
      a higher probability of visiting the GP than other social classes, but a lower
      probability of visiting a specialist or dentist. No large class differences were
      observed in frequency of hospitalization or emergency services use, or in breast
      cancer screening or influenza vaccination; cervical cancer screening frequency
      was lower among women from social classes IV-V. The inequalities in specialist
      visits, dentist visits, and cervical cancer screening were larger among people
      with only NHS insurance than those with double health insurance. Social class
      differences in waiting times were observed for specialist visits, but not for GP
      visits. Men and women from social classes IV-V had longer waits for a specialist;
      this was most marked among people with only NHS insurance. Clearly, within the
      NHS, social class inequalities are still evident for some curative and preventive
      services. Further research is needed to identify the factors driving these
      inequalities and to tackle these factors from within the NHS. Priority areas
      include specialist services, dental care, and cervical cancer screening.

PMID- 20799675
TI  - Women's health in developing countries: beyond an investment?
AB  - Most international programs and policies devised to improve women's health in
      developing countries have been shaped by powerful agencies and development
      ideologies, including the tendency to view women solely through the lens of
      instrumentalism (i.e., as a means to an end). In a literature review, the authors
      followed the trail of instrumentalism by reviewing the different approaches and
      paradigms that have guided international development initiatives over the past 50
      years. The analysis focuses on three key approaches to international development:
      the economic development, public health, and women-gender approaches. The
      findings indicate that progressive changes have adopted a more inclusive
      development perspective that is potentially beneficial to women's health. On the
      other hand, most paradigms have largely viewed improving women's lives in
      general, and their health in particular, as an investment or a means to
      development rather than an end in itself. Public health strategies did not escape
      the instrumentalism entrenched in the broader development paradigms. Although
      there was an opportunity for progress in the 1990s with the emergence of the
      human development and human rights paradigms and critical advances in Cairo and
      Beijing promoting women's agency, the current Millennium Development Goals
      project seems to have relapsed into instrumentalism.

PMID- 20799676
TI  - Effects of modern forest management on winter grazing resources for reindeer in
      Sweden.
AB  - Boreal forests in Sweden are exploited in a number of ways, including forestry
      and reindeer husbandry. In the winter, reindeer feed mainly on lichens, and
      lichen-rich forests are a key resource in the herding system. Commercial forestry
      has mainly negative effects on reindeer husbandry, and conflicts between these
      two industries have escalated over the last century. This article reviews the
      effects of modern forest management practices on the winter resources available
      for reindeer husbandry. Forestry affects reindeer husbandry at both the stand
      level and the landscape level and over various time scales. Clear-cutting, site
      preparation, fertilization, short rotation times, and forest fragmentation have
      largely resulted in a reduced amount of ground growing and arboreal lichens and
      restricted access to resource. This article also discusses alternative forestry
      practices and approaches that could reduce the impacts of forestry on reindeer
      husbandry, both in the short and long-term.

PMID- 20799678
TI  - Forest cover and stream flow in a headwater of the Blue Nile: complementing
      observational data analysis with community perception.
AB  - This study analyses the relation of forest cover and stream flow on the 266 km2
      Koga watershed in a headwater of Blue Nile Basin using both observed hydrological
      data and community perception. The watershed declined from 16% forest cover in
      1957 to 1% by 1986. The hydrological record did not reveal changes in the flow
      regime between 1960 and 2002 despite the reduction in forest area. This agrees
      with the perception of the downstream community living near the gauging station.
      The upstream community, however, reported both decreases in low flows and
      increases in high flows shortly after the forest cover was reduced. The upstream
      deforestation effect appeared to have been buffered by a wetland lower in the
      watershed. This study concludes that community perception can be a complement to
      observational data for better understanding how forest cover influences the flow
      regime.

PMID- 20799677
TI  - Damage caused to the environment by reforestation policies in arid and semi-arid
      areas of China.
AB  - Traditional approaches to ecosystem restoration have considered afforestation to
      be an important tool. To alleviate land degradation in China, the Chinese
      government has therefore invested huge amounts of money in planting trees.
      However, the results of more than half a century of large-scale afforestation in
      arid and semi-arid China have shown that when the trees are not adapted to the
      local environment, the policy does not improve the environment, and may instead
      increase environmental degradation. When precipitation is lower than potential
      evaporation, surface soil moisture typically cannot sustain forest vegetation,
      and shrubs or steppe species replace the forest to form a sustainable natural
      ecosystem that exists in a stable equilibrium with the available water supply.
      The climate of much of northwestern China appears to be unsuitable for
      afforestation owing to the extremely low rainfall. Although some small-scale or
      short-term afforestation efforts have succeeded in this region, many of the
      resulting forests have died or degraded over longer periods, so policymakers must
      understand that these small-scale or short-term results do not support an
      inflexible policy of large-scale afforestation throughout arid and semi-arid
      northwestern China. Rather than focusing solely on afforestation, it would be
      more effective to attempt to recreate natural ecosystems that are better adapted
      to local environments and that thus provide a better chance of sustainable, long
      term rehabilitation.

PMID- 20799679
TI  - The effects of habitat on coral bleaching responses in Kenya.
AB  - This study examines the bleaching responses of scleractinian corals at four sites
      in Kenya (Kanamai, Vipingo, Mombasa and Nyali) representing two distinct lagoon
      habitats (relatively shallow and relatively deep). Bleaching incidence was
      monitored for the whole coral community, while zooxanthellae densities and
      chlorophyll levels were monitored for target species (Pocillopora damicornis,
      Porites lutea, and Porites cylindrica) during a non-bleaching year (2006) and a
      year of mild-bleaching (2007). Differences in bleaching responses between
      habitats were observed, with shallower sites Kanamai and Vipingo exhibiting lower
      bleaching incidence than deeper sites Nyali and Mombasa. These shallower lagoons
      display more fluctuating thermal and light environments than the deeper sites,
      suggesting that corals in the shallower lagoons have acclimatized and/or adapted
      to the fluctuating environmental conditions they endure on a daily basis and have
      become more resistant to bleaching stress. In deeper sites that did exhibit
      higher bleaching (Mombasa and Nyali), it was found that coral recovery occurred
      more quickly in the protected area than in the non-protected area.

PMID- 20799680
TI  - The links between resource dependency and attitude of commercial fishers to coral
      reef conservation in the Red Sea.
AB  - The imperative to further constrain extractive uses of natural resources will
      strengthen as resources degrade through over-use or exposure to climate changes.
      Here, we explore an approach to increase the support for marine conservation
      among coral reef fishers. We explore the proposition that resource dependency in
      the Egyptian Red Sea can act as a barrier to conservation. We administered face
      to-face surveys to 49% of the fishing industry to: (i) identify the level of
      compliance to the local marine protected area (MPA), (ii) assess the level of
      dependency on marine resources in the region and (iii) examine the relationship
      between resource dependency and conservation attitudes. Only 11.4% of fishers
      were aware of the MPA. Fishers were mostly limited in their social flexibility
      and livelihood options. Results suggest that resource dependency is highly and
      negatively correlated with conservation attitudes suggesting that management
      efforts need to seriously focus on reducing dependency if conservation goals are
      to be met.

PMID- 20799681
TI  - Trends in ecosystem service research: early steps and current drivers.
AB  - Over the past 50 years, human beings have influenced ecosystems more rapidly than
      at any similar time in human history, drastically altering ecosystem functioning.
      Along with ecosystem transformation and degradation, a number of studies have
      addressed the functioning, assessment and management of ecosystems. The concept
      of ecosystem services has been developed in the scientific literature since the
      end of the 1970s. However, ecosystem service research has focused on certain
      service categories, ecosystem types, and geographical areas, while substantial
      knowledge gaps remain concerning several aspects. We assess the development and
      current status of ecosystem service research on the basis of publications
      collected from the Web of Science. The material consists of (1) articles (n =
      353) from all the years included in the Web of Science down to the completion of
      the Millennium Ecosystem Assessment and (2) more recent articles (n = 687)
      published between 2006 and 2008. We also assess the importance of international
      processes, such as the Convention on Biological Diversity, the Kyoto Protocol and
      the Millennium Ecosystem Assessment, as drivers of ecosystem service research.
      Finally, we identify future prospects and research needs concerning the
      assessment and management of ecosystem services.

PMID- 20799682
TI  - Community-based participatory research helps farmers and scientists to manage
      invasive pests in the Ecuadorian Andes.
AB  - Participatory research has not been a conspicuous methodology in developing
      nations for studying invasive pests, an increasing threat to the sustainable
      development in the tropics. Our study presents a community-based monitoring
      system that focuses on three invasive potato tuber moth species (PTM). The
      monitoring was developed and implemented by young farmers in a remote mountainous
      area of Ecuador. Local participants collected data from the PTM invasion front,
      which revealed clear connection between the abundance of one of the species
      (Tecia solanivora) and the remoteness to the main market place. This suggests
      that mechanisms structuring invasive populations at the invasion front are
      different from those occurring in areas invaded for longer period. Participatory
      monitoring with local people may serve as a cost-effective early warning system
      to detect and control incipient invasive pest species in countries where the
      daily management of biological resources is largely in the hands of poor rural
      people.

PMID- 20799683
TI  - Fighting corruption to save the environment: Cameroon's experience.

PMID- 20799684
TI  - Combating climate change: what will China's forestry industry do?

PMID- 20799685
TI  - Fish migration, dams, and loss of ecosystem services in the Mekong basin.
AB  - The past decade has seen increased international recognition of the importance of
      the services provided by natural ecosystems. It is unclear however whether such
      international awareness will lead to improved environmental management in many
      regions. We explore this issue by examining the specific case of fish migration
      and dams on the Mekong river. We determine that dams on the Mekong mainstem and
      major tributaries will have a major impact on the basin's fisheries and the
      people who depend upon them for food and income. We find no evidence that current
      moves towards dam construction will stop, and consider two scenarios for the
      future of the fisheries and other ecosystems of the basin. We conclude that major
      investment is required in innovative technology to reduce the loss of ecosystem
      services, and alternative livelihood strategies to cope with the losses that do
      occur.

PMID- 20799686
TI  - Raptor pit mortality in Mongolia and a call to identify and modify death traps
      wherever they occur.

PMID- 20799688
TI  - Nanomechanics of lipid bilayers: heads or tails?
AB  - Understanding the effect of mechanical stress on membranes is of primary
      importance in biophysics. Here we use force spectroscopy AFM to quantitatively
      characterize the nanomechanical stability of supported lipid bilayers as a
      function of their chemical composition. The onset of plastic deformation reveals
      itself as a repetitive jump in the approaching force curve, which represents a
      molecular fingerprint for the bilayer mechanical stability. By systematically
      probing a set of chemically distinct supported lipid bilayers (SLBs), we first
      show that both the headgroup and tail have a decisive effect on their mechanical
      properties. While the mechanical stability of the probed SLBs linearly increases
      by 3.3 nN upon the introduction of each additional -CH(2)- in the chain, it
      exhibits a significant dependence on the phospholipid headgroup, ranging from 3
      nN for DPPA to 66 nN for DPPG. Furthermore, we also quantify the reduction of the
      membrane mechanical stability as a function of the number of unsaturations and
      molecular branching in the chemical structure of the apolar tails. Finally, we
      demonstrate that, upon introduction of cholesterol and ergosterol, contrary to
      previous belief the mechanical stability of membranes not only increases linearly
      in the liquid phase (DLPC) but also for phospholipids present in the gel phase
      (DPPC). Our results are discussed in the framework of the continuum nucleation
      model. This work highlights the compelling effect of subtle variations in the
      chemical structure of phospholipid molecules on the membrane response when
      exposed to mechanical forces, a mechanism of common occurrence in nature.

PMID- 20799687
TI  - Characterization of the N-acetyl-alpha-D-glucosaminyl l-malate synthase and
      deacetylase functions for bacillithiol biosynthesis in Bacillus anthracis .
AB  - Bacillithiol (Cys-GlcN-malate, BSH) has recently been identified as a novel low
      molecular weight thiol in Bacillus anthracis, Staphylococcus aureus, and several
      other Gram-positive bacteria lacking glutathione and mycothiol. We have now
      characterized the first two enzymes for the BSH biosynthetic pathway in B.
      anthracis, which combine to produce alpha-d-glucosaminyl l-malate (GlcN-malate)
      from UDP-GlcNAc and l-malate. The structure of the GlcNAc-malate intermediate has
      been determined, as have the kinetic parameters for the BaBshA
      glycosyltransferase (->GlcNAc-malate) and the BaBshB deacetylase (->GlcN-malate).
      BSH is one of only two natural products reported to contain a malyl glycoside,
      and the crystal structure of the BaBshA-UDP-malate ternary complex, determined in
      this work at 3.3 A resolution, identifies several active-site interactions
      important for the specific recognition of l-malate, but not other alpha-hydroxy
      acids, as the acceptor substrate. In sharp contrast to the structures reported
      for the GlcNAc-1-d-myo-inositol-3-phosphate synthase (MshA) apo and ternary
      complex forms, there is no major conformational change observed in the structures
      of the corresponding BaBshA forms. A mutant strain of B. anthracis deficient in
      the BshA glycosyltransferase fails to produce BSH, as predicted. This B.
      anthracis bshA locus (BA1558) has been identified in a transposon-site
      hybridization study as required for growth, sporulation, or germination [Day, W.
      A., Jr., Rasmussen, S. L., Carpenter, B. M., Peterson, S. N., and Friedlander, A.
      M. (2007) J. Bacteriol. 189, 3296-3301], suggesting that the biosynthesis of BSH
      could represent a target for the development of novel antimicrobials with broad
      spectrum activity against Gram-positive pathogens like B. anthracis. The
      metabolites that function in thiol redox buffering and homeostasis in Bacillus
      are not well understood, and we present a composite picture based on this and
      other recent work.

PMID- 20799689
TI  - pH-operated nanopistons on the surfaces of mesoporous silica nanoparticles.
AB  - The development of drug delivery systems for the targeted and on-demand release
      of pharmaceutical products has risen rapidly to become a contemporary challenge
      in the field of nanobiotechnology. Biocompatible mechanized phosphonate-clothed
      silica nanoparticles have been designed and fabricated in which the
      supramolecular machinery, which covers the surfaces of the nanoparticles, behaves
      like nanopistons, releasing encapsulated guest molecules in a controlled fashion
      under acidic conditions. The mechanized nanoparticles consist of a monolayer of
      beta-cyclodextrin (beta-CD) rings positioned selectively around the orifices of
      the nanopores of the mesoporous nanoparticles. A rhodamine B/benzidine conjugate
      was prepared for use as the nanopistons for movement in and out of the
      cylindrical cavities provided by the beta-CD rings on the surfaces of the
      nanoparticles. Luminescence experiments indicated that the mechanized
      nanoparticles were able to store small cargo molecules (e.g., 2,6
      naphthalenedisulfonic acid disodium) within their nanopores at neutral pH and
      then release them by passage through the cavities of the beta-CD rings as soon as
      the pH was lowered to ~5. In further investigations, the phosphonate-covered
      silica nanoparticles were functionalized selectively with the beta-CD rings, but
      on this occasion, the seven linkers attaching the rings to the orifices
      surrounding the nanopores contained cleavable imine double bonds. The beta-CD
      rings on the surface of the nanoparticles served as gates for the storage of
      large cargo molecules (e.g., rhodamine B) inside the nanopores of the
      nanoparticles under neutral conditions. Since imine bonds can be hydrolyzed under
      acidic conditions, the beta-CD rings could be severed from the surface of the
      nanoparticles when the pH was decreased to 6, releasing the large cargo
      molecules. The results described here present a significant step toward the
      development of pH-responsive nanoparticle-based dual drug delivery vehicles that
      are potentially capable of being interfaced with biological systems.

PMID- 20799690
TI  - National study of exposure to pesticides among professional applicators: an
      investigation based on urinary biomarkers.
AB  - Epidemiologic studies of pesticides have been subject to important biases arising
      from exposure misclassification. Although turf applicators are exposed to a
      variety of pesticides, these exposures have not been well characterized. This
      paper describes a repeated measures study of 135 TruGreen applicators over three
      spraying seasons via the collection of 1028 urine samples. These applicators were
      employed in six cities across the United States. Twenty-four-hour estimates (MUg)
      were calculated for the parent compounds 2,4-D, MCPA, mecoprop, dicamba, and
      imidacloprid and for the insecticide metabolites MPA and 6-CNA. Descriptive
      statistics were used to characterize the urinary levels of these pesticides,
      whereas mixed models were applied to describe the variance apportionment with
      respect to city, season, individual, and day of sampling. The contributions to
      the overall variance explained by each of these factors varied considerably by
      the type of pesticide. The implications for characterizing exposures in these
      workers within the context of a cohort study are discussed.

PMID- 20799691
TI  - Synthesis of 7-hydroperoxycholesterol and its separation, identification, and
      quantification in cholesterol heated model systems.
AB  - 7-Hydroperoxycholesterol is considered to be an intermediate compound of the
      cholesterol oxidation path as the first product formed when cholesterol is
      oxidized by triplet oxygen. However, there is a limitation on cholesterol
      mechanism studies because of the lack of 7-hydroperoxycholesterol analytical
      standard due to its low stability. To verify the formation of hydroperoxides in
      cholesterol model systems heated at 140, 180, and 220  degrees C, 7alpha
      hydroperoxycholesterol was synthesized by cholesterol photooxidation followed by
      rearrangement at room temperature in chloroform. Its structure was confirmed on
      the basis of 13C NMR and mass spectra obtained by APCI-LC-MS. The synthesized
      compound was also used as standard for the quantification of 7
      hydroperoxycholesterol as the sum of 7alpha- and 7beta-hydroperoxycholesterol.
      The results demonstrated that 7-hydroperoxycholesterol is the first compound
      formed when the temperature is lower (140  degrees C). However, the concentration
      of the 7-hydroperoxycholesterol depends on the temperature and time of exposure:
      the higher the time, the higher the amount of 7-hydroperoxycholesterol at lower
      temperatures, and the lower the time, the lower the amount of 7
      hydroperoxycholesterol at higher temperatures (180 and 220  degrees C). By the
      formation of 7-hydroperoxycholesterol, the known cholesterol oxidation mechanism
      in three phases (initiation, propagation, and termination) could be confirmed;
      once at lower temperatures, the stage of cholesterol oxidation is at initiation,
      at which hydroperoxide formation predominates.

PMID- 20799692
TI  - Plant-produced trastuzumab inhibits the growth of HER2 positive cancer cells.
AB  - To study the agricultural production of biosimilar antibodies, trastuzumab
      (Herceptin) was expressed in Nicotiana benthamiana using the magnICON viral-based
      transient expression system. Immunoblot analyses of crude plant extracts revealed
      that trastuzumab accumulates within plants mostly in the fully assembled
      tetrameric form. Purification of trastuzumab from N. benthamiana was achieved
      using a scheme that combined ammonium sulfate precipitation with affinity
      chromatography. Following purification, the specificity of the plant-produced
      trastuzumab for the HER2 receptor was compared with Herceptin and confirmed by
      western immunoblot. Functional assays revealed that plant-produced trastuzumab
      and Herceptin have similar in vitro antiproliferative effects on breast cancer
      cells that overexpress HER2. Results confirm that plants may be developed as an
      alternative to traditional antibody expression systems for the production of
      therapeutic mAbs.

PMID- 20799693
TI  - 3'-Deoxy phosphoramidate dinucleosides as improved inhibitors of hepatitis C
      virus subgenomic replicon and NS5B polymerase activity.
AB  - Phosphoramidate dinucleosides named "GC 3'-OH" series, carrying various
      phosphoramidate linkages have been previously reported as hepatitis C virus (HCV)
      inhibitors. To enhance the efficacy of these dinucleotides, we synthesized a
      novel "GC 3'-H" series as potential chain terminators. We showed that their
      inhibition potency is strongly increased by the introduction of novel neutral and
      bis-negatively charged phosphoramidate side chains. Their inhibitory effect on
      HCV NS5B polymerase was evaluated in vitro and in HCV subgenomic replicon
      containing Huh-6 cells. As expected, 3'-H compounds are more potent than their 3'
      OH counterparts to inhibit HCV polymerase activity. The most potent inhibitor, a
      5'-phosphorylated dinucleotide bearing a bis-negatively charged amino side chain
      (7), exhibits an IC(50) value of 8 MUM in vitro and EC(50) value of 2.6 MUM in
      the HCV subgenomic replicon system. A molecular structure model is presented to
      propose an interpretation of the gain afforded by the of 3'-H-cytidine
      modification.

PMID- 20799694
TI  - Nanoscale investigation of the impact of pH and orthophosphate on the corrosion
      of copper surfaces in water.
AB  - Advanced surface characterization techniques were used to systematically
      investigate either the corrosion or passivation of copper after immersion in
      water as impacted by pH and orthophosphate water chemistries. Atomic force
      microscopy, depth profiling with time-of-flight secondary ion mass spectrometry,
      and X-ray diffraction were used to evaluate changes in surface chemistry of
      copper surfaces resulting from various chemical treatments. Nanoscale differences
      in surface morphology are clearly evident after 6 and 24 h immersion in water
      samples. Orthophosphate and pH dramatically influence the evolution and
      progression of changes during surface corrosion. For example, in the absence of
      orthophosphate the surface of copper exposed to water at pH 6 had formed
      relatively large cubic crystals on the surface up to 400 nm in height. In the
      presence of orthophosphate, the morphology and growth rate of corrosion byproduct
      changed dramatically, and the formation of identifiable crystals diminished.
      These investigations provide insight into the mechanisms of surface passivation
      and the evolution of nanoscale mineral deposits on surfaces at very early stages
      of the corrosion of copper surfaces in water.

PMID- 20799695
TI  - Replicable multilayered nanofibrous patterns on a flexible film.
AB  - This report describes a simple method for the direct patterning of nanofibers on
      a flexible, insulating film. The method allows the replication of nanofibrous
      patterns from a single patterned electrode and the fabrication of multilayered
      patterns from various electrode shapes. The architecture of the fibrous patterns
      can be controlled by tailoring the ambient humidity, thickness of the insulating
      film, polarity of the electrode, and size of the patterned electrode. Using this
      novel technique, it is possible to fabricate various complex patterns of
      nanofibers as well as inexpensive patterned structures.

PMID- 20799696
TI  - The pH induced sol-gel transition in skim milk revisited. A detailed study using
      time-resolved light and x-ray scattering experiments.
AB  - We present a detailed study of the evolution of the size, structure and stability
      of casein micelles upon acidification of skim milk typically applied in yogurt
      making processes using a combination of time-resolved light and small-angle X-ray
      scattering experiments. While most of the available light scattering studies on
      casein acidification have been restricted to transparent and therefore highly
      diluted samples, we now profit from a newly developed multiangle 3D light
      scattering instrument, which allows for time-resolved measurements in highly
      turbid samples. Our experiments clearly demonstrate the presence of two parallel
      pH-dependent processes, micellar reassembly and aggregation. Using a systematic
      investigation of the effect of casein concentration, acidification rate, and
      ionic strength, we are able to decouple these two processes and obtain detailed
      information about the pH-induced restructuration of the casein micelle structure
      that occurs prior to destabilization. Moreover, our experiments also
      unambiguously demonstrate that these micellar reassembly processes are highly
      concentration dependent, and that typical light scattering studies conducted
      under highly diluted conditions are resulting in findings that may not be
      relevant for the situation encountered in industrial processes at higher
      concentrations. Experiments conducted with covalently cross-linked micelles,
      where the pH-induced reassembly has been suppressed, further confirm our
      findings. 

PMID- 20799697
TI  - Controlled assembly of Janus nanoparticles.
AB  - Janus nanoparticles were prepared by interfacial ligand exchange reactions of
      octanethiolate-protected gold (AuC8) nanoparticles with 3-mercapto-1,2
      propanediol (MPD) at the air/water interface. AFM and TEM measurements showed
      that the resulting particles formed stable aggregates in water with dimensions up
      to a few hundred nanometers, in sharp contrast to the original AuC8 particles and
      bulk-exchange counterparts where the aggregates were markedly smaller. Consistent
      behaviors were observed in dynamic light scattering measurements. FTIR
      measurements of solid films of the nanoparticles suggested that the
      octanethiolate ligands were mostly of trans conformation, whereas the MPD ligands
      exhibited gauche defects as a consequence of the hydrogen-bonding interactions
      between the hydroxyl moieties of adjacent ligands. Raman spectroscopic
      measurements in an aqueous solution of pyridine showed that the pyridine ring
      breathing modes remained practically unchanged and the intensity profiles
      indicated minimal interactions between pyridine and the gold cores within the
      three nanoparticle ensembles. However, water bending vibrational features were
      found to be enhanced substantially with the addition of Janus nanoparticles,
      which was ascribed to the formation of clusters of water molecules that were
      trapped within the nanoparticle ensembles. No apparent enhancement was observed
      with the AuC8 or bulk-exchange particles.

PMID- 20799698
TI  - Electrocatalytic oxygen reduction on functionalized gold nanoparticles
      incorporated in a hydrophobic environment.
AB  - The electrocatalytic properties of gold nanoparticles covalently capped with a
      monolayer film of 1,4-decylphenyl groups for oxygen reduction in an alkaline
      solution have been studied. Functionalized nanoparticles were adsorbed on a film
      of the same capping ligand previously grafted to a glassy carbon electrode. The
      molecular film-nanoparticle assembly was characterized by cyclic voltammetry and
      XPS. It is shown that although the attachment of the capping ligand to the
      electrode surface blocks direct electron transfer, the metal centers of the
      incorporated nanoparticles provide sites for electron tunneling from the
      electrode surface thus leading to sites where oxygen reduction can take place.
      Rotating disk voltammetry shows that the oxygen reduction reaction follows mainly
      a peroxide formation channel on these nanostructured surfaces. The capping ligand
      greatly influences the reduction mechanism by establishing a local hydrophobic
      environment at the reaction centers within the film.

PMID- 20799699
TI  - Remarkable reduction of thermal conductivity in silicon nanotubes.
AB  - We propose to reduce the thermal conductivity of silicon nanowires (SiNWs) by
      introducing a small hole at the center, i.e., construct a silicon nanotube (SiNT)
      structure. Our numerical results demonstrate that a very small hole (only 1%
      reduction in cross section area) can induce a 35% reduction in room temperature
      thermal conductivity. Moreover, with the same cross section area, thermal
      conductivity of SiNT is only about 33% of that of SiNW at room temperature. The
      spatial distribution of vibrational energy reveals that localization modes are
      concentrated on the inner and outer surfaces of SiNTs. The enhanced surface-to
      volume ratio in SiNTs reduces the percentage of delocalized modes, which is
      believed to be responsible for the reduction of thermal conductivity. Our study
      suggests SiNT is a promising thermoelectric material with low thermal
      conductivity.

PMID- 20799700
TI  - Purification, identification, and characterization of methylcobalamin from
      Spirulina platensis.
AB  - The present study reports methylcobalamin in Spirulina platensis using high
      performance liquid chromatography (HPLC), thin-layer chromatography (TLC),
      microbiological assay, chemiluminescence assay, liquid chromatography-mass
      spectrometry (LC-MS), and tandem mass spectrometry (MS/MS). Extraction of vitamin
      B12 from S. platensis was carried out without using cyanide. Partial purification
      was achieved using Amberlite XAD-2 followed by elution with 80% (v/v) methanol.
      Activated charcoal facilitated removal of impurities in S. platensis extract and
      in further purification of vitamin B12. The purified fraction was identified to
      contain methylcobalamin as analyzed by HPLC and TLC. Authenticity of
      methylcobalamin was further confirmed by LC-MS and MS/MS. Quantitation of
      methylcobalamin in a test sample of S. platensis biomass was performed using
      microbiological assay and chemiluminescence assay and was found to be 38.5+/-2
      and 35.7+/-2 MUg/100 g of dry biomass, respectively.

PMID- 20799701
TI  - Effects of protocatechuic acid on trans fat induced hepatic steatosis in mice.
AB  - The effects of protocatechuic acid (PCA) on hepatic activity and/or mRNA
      expression of lipogenic enzymes and sterol regulatory element-binding proteins
      (SREBPs) in mice fed a trans fatty acid (TFA)-rich diet were examined. PCA at 1,
      2, or 4% was provided for 10 weeks. Results showed that TFA diet significantly
      enhanced hepatic activity and mRNA expression of fatty acid synthase, 3-hydroxy-3
      methylglutaryl coenzyme A reductase, stearoyl-CoA desaturase-1, and SREBP-1c
      (P<0.05); however, the intake of PCA significantly diminished the activity and
      mRNA expression of these lipogenic factors and decreased hepatic lipid
      accumulation (P<0.05). TFA diet significantly increased hepatic levels of TFA and
      pro-inflammatory cytokines (P<0.05). However, PCA intake significantly lowered
      hepatic content of 18:1 trans and 18:2 trans, as well as reduced the level of
      test cytokines (P<0.05). These results indicate that PCA is a potent agent for
      attenuating TFA-induced hepatic steatosis.

PMID- 20799702
TI  - Use of total reflection X-ray fluorescence (TRXF) for the quantification of DNA
      binding to lipid monolayers at the air-water interface.
AB  - To use the TRXF technique for the quantification of DNA binding to monolayers at
      the air-water interface, DNA from salmon testes was labeled by covalently bound
      bromine. For this purpose, an analytical procedure for the quantification of
      bromine in labeled DNA with a detection limit of 10-20 MUg was developed. It was
      found that the pH of the solution has a strong influence on the yield of
      brominated DNA (BrDNA) when Br(2) is used as a reagent. Much higher degrees of
      bromination can be achieved at pH 5 than at pH 7. A degree of bromination above a
      threshold of 2 to 3% (bromine per base) leads to the cross linking of BrDNA with
      the formation of an insoluble gel during the precipitation procedure. Finally, a
      reaction scheme with N-bromosuccinimide (NBS) that avoids precipitation has been
      established. Succinimide and some bromide ions remain in the solution as
      byproducts. However, these bromide ions are not competitive with BrDNA for
      binding at positively charged monolayers. Therefore, a new method for binding
      studies of model DNA to Langmuir monolayers at the air-water interface has been
      established. An important result of these studies is the finding that higher salt
      concentrations (representing physiological conditions) lead to an increased
      amount of adsorbed DNA. This can be explained by the decrease in the effective
      charge of the DNA molecules with decreasing Debye screening length.

PMID- 20799703
TI  - Synthesis and structure-activity relationship study of deoxybenzoins on relaxing
      effects of porcine coronary artery.
AB  - Deoxybenzoins are potent antioxidants and tyrosinase inhibitors with potential to
      be developed as food preservatives and cosmetic ingredients. To explore the
      potential in cardiovascular protection, 25 polyphenolic deoxybenzoins were
      synthesized and evaluated for inhibitory effects on KCl-induced porcine coronary
      arterial contraction. The results revealed deoxybenzoins are significant
      inhibitors of KCl-induced arterial contraction. Among those synthesized, two
      thirds of the deoxybenzoins exhibited moderate to good efficacy on relaxing
      contracted artery including 2,4-dihydroxydeoxybenzoin with EC50=3.30 MUM
      (Emax=100%, n=7) and 2,4-dihydroxy-4'-methoxydeoxybenzoin EC50=3.70 MUM
      (Emax=100%, n=5). Deoxybenzoins displayed an endothelium-dependent relaxing
      manner on the contracted artery; the contractile responses of neither endothelium
      denuded nor L-NAME deactivated rings were inhibited. The structure-activity
      relationships of deoxybenzoin on arterial relaxing effects concluded that the 2,4
      dihydroxylated deoxybenzoins presented a potential vascular relaxing
      pharmacophore, with favoring substitution on ring B in the order of H>=p-OMe>p
      OH>o-OMe>m,p-diOMe>=m-OMe.

PMID- 20799704
TI  - Surface-induced rearrangement of polyelectrolyte complexes: influence of complex
      composition on adsorbed layer properties.
AB  - The adsorption characteristics of two different types of polyelectrolyte
      complexes (PECs), prepared by mixing poly(allylamine hydrochloride) and
      poly(acrylic acid) in a confined impinging jet (CIJ) mixer, have been
      investigated with the aid of stagnation point adsorption reflectometry (SPAR), a
      quartz crystal microbalance with dissipation (QCM-D), and atomic force microscopy
      (AFM) using SiO(2) surfaces. The two sets of PEC were prepared by combining high
      molecular mass PAH/PAA (PEC-A) and low molecular mass PAH/PAA (PEC-B). The PEC-A
      showed a higher adsorption to the SiO(2) surfaces than the PEC-B. The adsorption
      of the PEC-A also showed a larger change in the dissipation (DeltaD), according
      to the QCM-D measurements, suggesting that the adsorbed layer of these complexes
      had a relatively lower viscosity and a lower shear modulus. Complementary
      investigations of the adsorbed layer using AFM imaging showed that the adsorbed
      layer of PEC-A was significantly different from that of PEC-B and that the
      changes in properties with adsorption time were very different for the two types
      of PECs. The PEC-A complexes showed a coalescence into larger block of complexes
      on the SiO(2) surface, but this was not detected with the PEC-B. The size
      determinations of the complexes in solution showed that they were very stable
      over time, and it was therefore concluded that the coalescence of the complexes
      was induced by the interaction between the complexes and the surface. The results
      also indicated that polyelectrolytes can migrate between the different complexes
      adsorbed to the surface. The results also give indications that the preparation
      of PEC-B leads to the formation of two different types of polyelectrolyte
      complexes differing in the amount of polymer in the complexes; i.e., two
      populations of complexes were formed with similar sizes but with totally
      different adsorption structures at the solid-liquid interface.

PMID- 20799705
TI  - Selective acetylation of per-O-TMS-protected monosaccharides.
AB  - Selective acetylation of various per-O-TMS-protected carbohydrates has been
      accomplished. Using a protecting group exchange strategy and microwave
      assistance, monosaccharides (glucose, galactose, and mannose) can be selectively
      acetylated producing either the 6-O-monoacetate or 1,6-O-diacetylated species.
      This new class of molecules can be deprotected without migration of the acetyl
      groups, providing useful synthetic intermediates. To demonstrate the scope of the
      reaction, the methodology was successfully extended to TMS-protected ceramide.

PMID- 20799706
TI  - Protein aggregation in white wines: influence of the temperature on aggregation
      kinetics and mechanisms.
AB  - High temperatures (typically 80  degrees C) are widely used to assess wine
      stability with regard to protein haze or to study mechanisms involved in their
      formation. Dynamic light scattering experiments were performed to follow
      aggregation kinetics and aggregate characteristics in white wines at different
      temperatures (30-70  degrees C). Aggregation was followed during heating and
      cooling to 25  degrees C. Results were coupled with the study of the time
      temperature dependence of heat-induced protein aggregation. At low temperature
      (40  degrees C), aggregation developed during heating. Colloidal equilibria were
      such that attractive interactions between species led to the rapid formation of
      micrometer-sized aggregates. At higher temperatures (60 and 70  degrees C),
      enhanced protein precipitation was expected and observed. However, high
      temperatures prevented aggregation, which mainly developed during cooling.
      Depending on the wine, cooling induced the formation of sub-micronic metastable
      aggregates stabilized by electrostatic repulsions, or the rapid formation of
      micrometer-sized aggregates, prone to sedimentation.

PMID- 20799707
TI  - Highly sensitive microplate chemiluminescence enzyme immunoassay for the
      determination of staphylococcal enterotoxin B based on a pair of specific
      monoclonal antibodies and its application to various matrices.
AB  - A highly specific and sensitive microplate chemiluminescent enzyme immunoassay
      (CLEIA) was established and validated for the detection of staphylococcal
      enterotoxin B (SEB). A pair of monoclonal antibodies (mAbs) that recognizes
      different epitopes of SEB was selected from 20 SEB-specific mAbs, and the
      experimental conditions were examined and optimized for the development of the
      CLEIA. This method exhibited high performance with a dynamic range of 0.01-5
      ng/mL, and the measured limit of detection (LOD) was 0.01 ng/mL. Intra- and
      interassay coefficient variations were all lower than 13% at three concentrations
      (0.2, 0.4, and 2 ng/mL). For specificity studies, when this method was applied to
      test staphylococcal enterotoxins A, C1, and D, no cross-reactivity was observed.
      It has been successfully applied to the analysis of SEB in a variety of
      environmental, biological and humoral matrices such as sewage, tap water, river
      water, roast beef, peanut butter, cured ham, 10% nonfat dry milk, milk, orange
      juice, and human urine and serum. The aim of this article is to show that the
      highly sensitive, specific, and simple microplate CLEIA, based on a pair of
      highly specific monoclonal antibodies, has potential applications for quantifying
      SEB in public health and military reconnaissance.

PMID- 20799708
TI  - Light-induced switching of the wettability of novel asymmetrical poly(vinyl
      alcohol)-co-ethylene membranes blended with azobenzene polymers.
AB  - Novel composite asymmetrical membranes based on poly(vinyl alcohol)-co-ethylene
      (EVAL) as the host material and new polyethers that contain azobenzene moieties
      in the side chain were prepared by dry-cast phase inversion after dissolving the
      azo polymers in tetrahydrofuran and EVAL in dimethylsulfoxide and subsequently
      mixing the resulting solutions. By taking advantage of the proper temperature
      variation in the oven used for solvent evaporation, asymmetrical membranes that
      exhibited a dense, crystalline layer on the bottom and a porous, mainly amorphous
      layer on the top were obtained. Remarkable changes in the surface morphology and
      the contact angle with water were observed on the top surfaces of the composite
      membranes. This was ascribed not only to the enhanced concentration of azo
      polymer on the top surface but mostly to a conformational change in EVAL induced
      by the photoisomerization of the guest azo groups, as shown by HRMAS (1)H NMR.
      The morphological and structural changes in EVAL could be reversed on exposing
      the membrane to visible light for 24 h.

PMID- 20799709
TI  - Comparative effects of cellulose and soluble fibers (pectin, konjac glucomannan,
      inulin) on fecal water toxicity toward Caco-2 cells, fecal bacteria enzymes, bile
      acid, and short-chain fatty acids.
AB  - The aim of this study was to compare the effects of cellulose and three soluble
      dietary fibers, pectin, konjac glucomannan (KGM), and inulin, on the cytotoxicity
      and DNA damage of fecal water-treated Caco-2 cells, a human colon adenocarcinoma
      cell line, and to investigate the fecal components that potentially modulate the
      fecal toxicity, that is, bacterial enzymes, bile acids, and short-chain fatty
      acids. Six-week-old BALB/cJ mice were randomly allocated to consume an AIN-93
      diet that contained no dietary fiber (fiber-free) or 5% (w/w) cellulose, pectin,
      KGM, and inulin for 3 weeks. Feces were collected during days 18-21. Fecal waters
      were co-incubated with Caco-2 cells to determine the cytotoxicity and DNA damage.
      In addition, the fecal bacterial enzymes, bile acids, and short-chain fatty acids
      were determined. Results indicated that all fiber diets similarly increased the
      survival rate (%) of fecal water-treated Caco-2 cells as compared with the fiber
      free diet. The inhibition of fecal water-induced DNA damage in Caco-2 cells was
      greater for the pectin and inulin diets than for the cellulose and KGM diets. In
      contrast, cellulose exerted the greatest inhibitory effect on the fecal beta
      glucuronidase activity. Cellulose and all soluble dietary fibers reduced the
      secondary bile acid concentrations in the fecal water, but only soluble fibers
      increased the fecal concentrations of short-chain fatty acids, as compared with
      no fiber. Therefore, this study suggests that all dietary fibers substantially
      reduced the fecal water toxicity, which is associated with decreased secondary
      bile acid levels by all fibers, reduced fecal beta-glucuronidase activity by
      cellulose, and increased short-chain fatty acid levels by soluble dietary fibers.

PMID- 20799710
TI  - Microporous Ni-doped TiO2 film photocatalyst by plasma electrolytic oxidation.
AB  - Ni-doped TiO2 film catalysts were prepared by a plasma electrolytic oxidation
      (PEO) method and were mainly characterized by means of SEM, EDS, XRD, XPS, and
      DRS, respectively. The effects of Ni doping on the structure, composition and
      optical absorption property of the film catalysts were investigated along with
      their inherent relationships. The results show that the film catalyst is composed
      of anatase and rutile TiO2 with microporous structure. Doping Ni changes the
      phase composition and the lattice parameters (interplanar crystal spacing and
      cell volume) of the films. The optical absorption range of TiO2 film gradually
      expands and shifts to the red with increasing dosages. Both direct and indirect
      transition band gaps of the TiO2 films are deduced consequently. Moreover, the
      photocatalytic activity of the film catalysts for splitting Na2S+Na2SO3 solution
      into H2 is enhanced by doping with an appropriate amount of Ni. The as-prepared
      TiO2 film catalyst doping with 10 g/L of Ni(Ac)2 presents the highest
      photocatalytic reducing activity.

PMID- 20799711
TI  - Peptide arrays for screening cancer specific peptides.
AB  - In this paper, we describe a novel method to screen peptides for specific
      recognition by cancer cells. Seventy peptides were synthesized on a cellulose
      membrane in an array format, and a direct method to study the peptide-whole cell
      interaction was developed. The relative binding affinity of the cells for
      different peptides with respect to a lead 12-mer p160 peptide, identified by
      phage display, was evaluated using the CyQUANT fluorescence of the bound cells.
      Screening allowed identification of at least five new peptides that displayed
      higher affinity (up to 3-fold) for MDA-MB-435 and MCF-7 human cancer cells
      compared to the p160 peptide. These peptides showed very little binding to the
      control (noncancerous) human umbilical vein endothelial cells (HUVECs). Three of
      these peptides were synthesized separately and labeled with fluorescein
      isothiocyanate (FITC) to study their uptake and interaction with the cancer and
      control cells using confocal laser scanning microscopy and flow cytometry. The
      results confirmed the high and specific affinity of an 11-mer peptide 11
      (RGDPAYQGRFL) and a 10-mer peptide 18 (WXEAAYQRFL) for the cancer cells versus
      HUVECs. Peptide 11 binds different receptors on target cancer cells as its
      sequence contains multiple recognition motifs, whereas peptide 18 binds mainly to
      the putative p160 receptor. The peptide array-whole cell binding assay reported
      here is a complementary method to phage display for further screening and
      optimization of cancer targeting peptides for cancer therapy and diagnosis.

PMID- 20799712
TI  - Binding of oxytetracycline to bovine serum albumin: spectroscopic and molecular
      modeling investigations.
AB  - The residue of the widely used veterinary drug oxytetracycline (OTC) in the
      environment (e.g., animal food, soils, surface water, and groundwater) is
      potentially harmful. Knowledge of its binding to proteins contributes to the
      understanding of its toxicity in vivo. This work establishes the binding mode of
      OTC with bovine serum albumin (BSA) under physiological conditions by
      spectroscopic methods and molecular modeling techniques. The inner filter effect
      was eliminated to get accurate data (binding parameters). On the basis of the
      thermodynamic results and site marker competition experiments, it was considered
      that OTC binds to site II (subdomain IIIA) of BSA mainly by electrostatic
      interaction. Furthermore, using the BSA model established with CPHmodels,
      molecular docking and some other molecular modeling methods were applied to
      further define that OTC interacts with the Arg 433, Arg 436, Ala 429, and Pro 516
      residues of BSA. In addition, UV-visible absorption, synchronous fluorescence,
      and circular dichroism (CD) results showed that the binding of OTC can cause
      conformational and some microenvironmental changes of BSA. The work provides
      accurate and full basic data for clarifying the binding mechanisms of OTC with
      BSA in vivo and is helpful for understanding its effect on protein function
      during its transportation and distribution in blood.

PMID- 20799714
TI  - Functional fluorinated modifications on a polyelectrolyte coated
      polydimethylsiloxane substrate for fabricating antibody microarrays.
AB  - Fluorinated compounds exhibit hydrophobic, nonstick, and self-cleaning
      properties, making them attractive for use as the coating material for biochips.
      In this study, we copolymerized the fluorinated compound 1H,1H,2H-perfluoro-1
      decene (FD) with acrylic acid (AA) and bonded the resulting copolymer with
      protein G on the surface of polyelectrolyte coated polydimethylsiloxane (PDMS) to
      form a functional surface that captures antibodies. We demonstrated that the
      modified PDMS surface remained hydrophobic while becoming resistant to
      nonspecific protein binding. Thus, aqueous sample solutions formed the droplets
      (4 MUL) on the surface without spreading and drying during the sample printing.
      Contact angle measurements showed that this functionalized surface was as
      hydrophobic as the native PDMS with a virtually constant contact angle over seven
      days of the study under dried condition at 4  degrees C. Spectroscopic
      measurements revealed that FD/AA copolymerization formed a homogeneous and highly
      dense multilayer (50 mg/mm(2)) with a fluorine coverage of 35.4%. Moreover,
      protein G was shown to covalently bind to AA molecules on the surface at a
      binding density of 0.24 MUg/mm(2). We demonstrated that the fluorinated coating
      withstood nonspecific binding with extremely low background emission, leading to
      bioassays that, without the need of blocking agents, exhibited six times more
      sensitivity than PEG coatings. The fluorinated PDMS antibody microarrays were
      further applied to accurately determine the absolute concentration of ERalpha in
      MCF-7 cells. In conclusion, the unique properties of fluorinated compounds, such
      as withstanding wetting, nonspecific binding and contamination, make them an
      excellent coating material for use in sensitive and simple on-chip assays.

PMID- 20799713
TI  - Matrix-free LDI mass spectrometry platform using patterned nanostructured gold
      thin film.
AB  - A novel matrix-free LDI MS platform using a thin film of patterned nanostructured
      gold, capped with methyl- and carboxy-terminated self-assembled monolayers (SAMs)
      is presented. Calibration on the matrix-free LDI surface was performed using a
      peptide standard mixture available for MALDI analysis. MS analysis for limit of
      detection was performed using angiotensin I peptide. Peptide fragments from
      standard protein digests of bovine serum albumin, bovine catalase, and bovine
      lactoperoxidase were used to carry out peptide mass fingerprinting analysis.
      Sequence coverage of each protein digest and the number of detected peptide
      fragments were compared with conventional MALDI MS on a standard MALDI plate.
      Versatility of the nanostructured gold LDI substrate is illustrated by performing
      MS analysis on a protein digest using different enzymes and by small molecule MS
      analysis.

PMID- 20799715
TI  - Synthesis and stabilization of a monomeric iron(II) hydroxo complex via
      intramolecular hydrogen bonding in the secondary coordination sphere.
AB  - Utilizing the pyridinediimine ligand [(2,6
      (i)PrC(6)H(3))N?CMe)(N((i)Pr)(2)C(2)H(4))N?CMe)C(5)H(3)N] (didpa), the iron(II)
      complexes Fe(didpa)Br(2) (1), [Fe(Hdidpa)Br(2)][PF(6)] (2), and
      [Fe(Hdidpa)CH(3)CN(OH)][2PF(6)] (3) were synthesized and characterized by X-ray
      diffraction and spectroscopic methods. The X-ray data show that the didpa
      scaffold is capable of forming intramolecular hydrogen bonds in the solid state
      located within the secondary coordination sphere of complexes 2 and 3. These
      hydrogen bonds are responsible for stabilizing the iron(II) hydroxo ligand in 3,
      which originates from H(2)O.

PMID- 20799716
TI  - Square coordinated MnO(2)-units in BiMn(7)O(12).
AB  - Room temperature high-resolution synchrotron X-ray diffraction (HRSXRD)
      measurements were carried out on polycrystalline samples of BiMn(7)O(12) and
      LaMn(7)O(12). Rietveld refinements of HRSXRD data describe the crystal structures
      of both compounds in the monoclinic space group I2/m. The maximum entropy method
      based pattern fitting (MPF) method inversion of HRSXRD data was utilized to
      obtain the spatial electron density (ED) distribution. Obtained results show
      clear differences in ED distributions around Mn-O bonds between isomorphic
      BiMn(7)O(12) and LaMn(7)O(12). The scheme of ED distributions in BiMn(7)O(12)
      indicates the presence of orbital ordering in the MnO(2) planar arrangement that
      appears as prominent features in very distorted MnO(12) and MnO(6) polyhedrons in
      the perovskite related structure of [BiMn(3)](A-site)[Mn(4)](B-site)O(12).

PMID- 20799717
TI  - Penetration of lipid membranes by gold nanoparticles: insights into cellular
      uptake, cytotoxicity, and their relationship.
AB  - Nanoparticle penetration into cell membranes is an interesting phenomenon that
      may have crucial implications on the nanoparticles' biomedical applications. In
      this paper, a coarse-grained model for gold nanoparticles (AuNPs) is developed
      (verified against experimental data available) to simulate their interactions
      with model lipid membranes. Simulations reveal that AuNPs with different signs
      and densities of surface charges spontaneously adhere to the bilayer surface or
      penetrate into the bilayer interior. The potential of mean force calculations
      show that the energy gains upon adhesion or penetration is significant. In the
      case of penetration, it is found that defective areas are induced across the
      entire surface of the upper leaflet of the bilayer and a hydrophilic pore that
      transports water molecules was formed with its surrounding lipids highly
      disordered. Penetration and its concomitant membrane disruptions can be a
      possible mechanism of the two observed phenomena in experiments: AuNPs bypass
      endocytosis during their internalization into cells and cytotoxicity of AuNPs. It
      is also found that both the level of penetration and membrane disruption increase
      as the charge density of the AuNP increases, but in different manners. The
      findings suggest a way of controlling the AuNP-cell interactions by manipulating
      surface charge densities of AuNPs to achieve designated goals in their biomedical
      applications, such as striking a balance between their cellular uptake and
      cytotoxicity in order to achieve optimal delivery efficiency as delivery agents.

PMID- 20799718
TI  - Tri- and tetranuclear nickel(II) inverse metallacrown complexes involving oximato
      oxygen linkers: role of the guest anion (oxo versus alkoxo) in controlling the
      size of the ring topology.
AB  - A trinuclear oximato complex, [(NiHL(1))(3)(MU(3)-O)]ClO(4) (1), with inverse
      metallacrown 9-MC-3 topology has been synthesized using a Schiff-base ligand
      (H(2)L(1)) formed by condensation of ethanolamine (Hea) and diacetylmonoxime
      (Hdamo). The diamagnetic compound has been characterized by electrospray
      ionization mass spectrometry as well as by single-crystal X-ray diffraction
      analysis. In the solid state, the alcoholic OH group in this molecule stays away
      from coordination. Surprisingly in a similar chemical reaction, when intact Hea
      and Hdamo have been used as ligands instead of their Schiff-base forms, the
      product obtained is a 12-MC-4-type metallacrown,
      (Et(3)NH)[Ni(4)(damo)(4)(Hea)(2)(ea)(2)](ClO(4))(3) (2), with a larger cavity
      size needed to accommodate a pair of hydrogen-bonded (O-H...O)(-) anions. Unlike
      in 1, the alcoholic OH groups in 2 take part in metal coordination. Compound 2 on
      being refluxed with lithium hydroxide in methanol is converted to 1 in almost
      quantitative yield. This appears to be a novel reaction type, leading to
      contraction of a metallacrown ring size. A family of 12-MC-4 Ni(4) metallacrowns
      in inverse topology, viz.,
      [Ni(4)(damo)(4)(H(2)dea)(2)(Hdea)(2)](ClO(4))(2).2H(2)O (3),
      [Ni(4)(dpko)(4)(Hea)(2)(ea)(2)](ClO(4))(2).4H(2)O (4), and
      [Ni(4)(mpko)(4)(Hmea)(2)(mea)(2)](ClO(4))(2) (5), have been synthesized following
      a methodology similar to that adopted for 2, using different combinations of free
      oximes [viz., dipyridylketonoxime (Hdpko) and methylpyridylketonoxime (Hmpko)]
      and amino alcohols [viz., diethanolamine (H(2)dea), and N-methylethanolamine
      (Hmea)]. Crystal and molecular structures of 3-5 have been reported, each
      involving either a quasi (in 3) or a perfect (in 4 and 5) square plane (S(4)
      symmetry) with four octahedral Ni centers occupying the corners, and serve as a
      backbone of puckered metallacrown rings that accommodate a pair of hydrogen
      bonded (O-H...O)(-) anions. Antiferromagnetic interactions within the [Ni(4)]
      core [J/k(B) ~ -20 to -27 K based on the following spin Hamiltonian: H = 
      2J(S(1).S(2) + S(2).S(3) + S(3).S(4) + S(4).S(1))] lead to an S(T) = 0 ground
      state for these complexes.

PMID- 20799719
TI  - Ring-opening polymerization of epsilon-caprolactone catalyzed by sulfonic acids:
      computational evidence for bifunctional activation.
AB  - The mechanism of ring-opening of epsilon-caprolactone by methanol catalyzed by
      trifluoromethane and methane sulfonic acids has been studied computationally at
      the DFT level of theory. For both elementary steps, the sulfonic acid was
      predicted to behave as a bifunctional catalyst. The nucleophilic addition
      proceeds via activation of both the monomer and the alcohol. The ring-opening
      involves the cleavage of the endo C-O bond of the tetrahedral intermediate with
      concomitant proton transfer. In both cases, the sulfonic acid acts as a proton
      shuttle via its acidic hydrogen atom and basic oxygen atoms. The computed
      activation barriers are consistent with the relatively fast polymerizations
      observed experimentally at room temperature with both catalysts.

PMID- 20799720
TI  - Highly selective detection of silver in the low ppt range with ion-selective
      electrodes based on ionophore-doped fluorous membranes.
AB  - Ionophore-doped sensing membranes exhibit greater selectivities and wider
      measuring ranges if their membrane matrixes are noncoordinating and solvate
      interfering ions poorly. This is particularly true for fluorous phases, which are
      the least polar and polarizable condensed phases known. In this work, fluorous
      membrane matrixes were used to prepare silver ion-selective electrodes (ISEs).
      Sensing membranes composed of perfluoroperhydrophenanthrene, sodium tetrakis[3,5
      bis(perfluorohexyl) phenyl]borate, and one of four fluorophilic Ag(+)-selective
      ionophores with one or two thioether groups were investigated. All electrodes
      exhibited Nernstian responses to Ag(+) in a wide range of concentrations. Their
      selectivities for Ag(+) over interfering ions were found to depend on host
      preorganization and the length of the -(CH(2))(n)- spacers separating the
      coordinating thioether group from the strongly electron withdrawing
      perfluoroalkyl groups. ISEs based on the most selective of the four ionophores,
      that is, 1,3-bis(perfluorodecylethylthiomethyl)benzene, provided much higher
      selectivities for Ag(+) over many alkaline and heavy metal ions than most Ag(+)
      ISEs reported in the literature (e.g., log K(Ag,J)(pot) for K(+), -11.6; Pb(2+), 
      10.2; Cu(2+), -13.0; Cd(2+), -13.2). Moreover, the use of this ionophore with a
      linear perfluorooligoether as membrane matrix and solid contacts consisting of
      three-dimensionally ordered macroporous (3DOM) carbon resulted in a detection
      limit for Ag(+) of 4.1 ppt (3.8 * 10(-1)1 M).

PMID- 20799721
TI  - NMR spectroscopic evidence for the intermediacy of XeF(3)(-) in XeF(2)/F(-)
      exchange, attempted syntheses and thermochemistry of XeF(3)(-) salts, and
      theoretical studies of the XeF(3)(-) anion.
AB  - The existence of the trifluoroxenate(II) anion, XeF(3)(-), had been postulated in
      a prior NMR study of the exchange between fluoride ion and XeF(2) in CH(3)CN
      solution. The enthalpy of activation for this exchange, DeltaH(?), has now been
      determined by use of single selective inversion (19)F NMR spectroscopy to be 74.1
      +/- 5.0 kJ mol(-1) (0.18 M) and 56.9 +/- 6.7 kJ mol(-1) (0.36 M) for equimolar
      amounts of [N(CH(3))(4)][F] and XeF(2) in CH(3)CN solvent. Although the XeF(3)(-)
      anion has been observed in the gas phase, attempts to prepare the Cs(+) and
      N(CH(3))(4)(+) salts of XeF(3)(-) have been unsuccessful, and are attributed to
      the low fluoride ion affinity of XeF(2) and fluoride ion solvation in CH(3)CN
      solution. The XeF(3)(-) anion would represent the first example of an AX(3)E(3)
      valence shell electron pair repulsion (VSEPR) arrangement of electron lone pair
      and bond pair domains. Fluorine-19 exchange between XeF(2) and the F(-) anion has
      also been probed computationally using coupled-cluster singles and doubles (CCSD)
      and density functional theory (DFT; PBE1PBE) methods. The energy-minimized
      geometry of the ground state shows that the F(-) anion is only weakly coordinated
      to XeF(2) (F(2)Xe---F(-); a distorted Y-shape possessing C(s) symmetry), while
      the XeF(3)(-) anion exists as a first-order transition state in the fluoride ion
      exchange mechanism, and is planar and Y-shaped (C(2v) symmetry). The molecular
      geometry and bonding of the XeF(3)(-) anion has been described and rationalized
      in terms of electron localization function (ELF) calculations, as well as the
      VSEPR model of molecular geometry. Quantum-chemical calculations, using the CCSD
      method and a continuum solvent model for CH(3)CN, accurately reproduced the
      transition-state enthalpy observed by (19)F NMR spectroscopy, and showed a
      negative but negligible enthalpy for the formation of the F(2)Xe---F(-) adduct in
      this medium.

PMID- 20799723
TI  - Flipping the switch on chloride concentrations with a light-active foldamer.
AB  - Here we demonstrate a bioinspired system where light stimulus is used to trigger
      the wavelength-dependent release and then reuptake of chloride ions in nonaqueous
      solutions. A chiral aryl-triazole foldamer with two azobenzene end groups has
      been synthesized to define a folded binding pocket for chloride ions that unfolds
      with UV light to liberate the chloride. The trans-dominated helical foldamer
      becomes less stable upon photoisomerization to the cis forms. Simultaneously, the
      observed binding affinity shows an ~10-fold reduction from K = 3000 M(-1) (MeCN,
      298 K). Control of chloride levels using light is demonstrated by switching the
      conductivity of an electrolyte solution up and down.

PMID- 20799722
TI  - Physical trapping of HIV-1 synaptic complex by different structural classes of
      integrase strand transfer inhibitors.
AB  - Raltegravir is an FDA approved inhibitor directed against human immunodeficiency
      virus type 1 (HIV-1) integrase (IN). In this study, we investigated the
      mechanisms associated with multiple strand transfer inhibitors capable of
      inhibiting concerted integration by HIV-1 IN. The results show raltegravir,
      elvitegravir, MK-2048, RDS 1997, and RDS 2197 all appear to encompass a common
      inhibitory mechanism by modifying IN-viral DNA interactions. These structurally
      different inhibitors bind to and inactivate the synaptic complex, an intermediate
      in the concerted integration pathway in vitro. The inhibitors physically trap the
      synaptic complex, thereby preventing target DNA binding and thus concerted
      integration. The efficiency of a particular inhibitor to trap the synaptic
      complex observed on native agarose gels correlated with its potency for
      inhibiting the concerted integration reaction, defined by IC(50) values for each
      inhibitor. At low nanomolar concentrations (<50 nM), raltegravir displayed a time
      dependent inhibition of concerted integration, a property associated with slow
      binding inhibitors. Studies of raltegravir-resistant IN mutants N155H and Q148H
      without inhibitors demonstrated that their capacity to assemble the synaptic
      complex and promote concerted integration was similar to their reported virus
      replication capacities. The concerted integration activity of Q148H showed a
      higher cross-resistance to raltegravir than observed with N155H, providing
      evidence as to why the Q148H pathway with secondary mutations is the predominant
      pathway upon prolonged treatment. Notably, MK-2048 is equally potent against wild
      type IN and raltegravir-resistant IN mutant N155H, suggesting this inhibitor may
      bind similarly within their drug-binding pockets.

PMID- 20799724
TI  - Columnar self-assembly of Cu2S hexagonal nanoplates induced by tin(IV)-X complex
      as inorganic surface ligand.
AB  - We have prepared columnar self-assembled Cu(2)S hexagonal nanoplates induced by a
      Sn-X complex for the first time and demonstrated that the Sn-X complex can affect
      not only the morphology of the nanocrystals but also the self-assembly ability of
      the nanocrystals.

PMID- 20799725
TI  - Compartmentalization and regulation of mitochondrial function by methionine
      sulfoxide reductases in yeast.
AB  - Elevated levels of reactive oxygen species can damage proteins. Sulfur-containing
      amino acid residues, cysteine and methionine, are particularly susceptible to
      such damage. Various enzymes evolved to protect proteins or repair oxidized
      residues, including methionine sulfoxide reductases MsrA and MsrB, which reduce
      methionine (S)-sulfoxide (Met-SO) and methionine (R)-sulfoxide (Met-RO) residues,
      respectively, back to methionine. Here, we show that MsrA and MsrB are involved
      in the regulation of mitochondrial function. Saccharomyces cerevisiae mutant
      cells lacking MsrA, MsrB, or both proteins had normal levels of mitochondria but
      lower levels of cytochrome c and fewer respiration-competent mitochondria. The
      growth of single MsrA or MsrB mutants on respiratory carbon sources was
      inhibited, and that of the double mutant was severely compromised, indicating
      impairment of mitochondrial function. Although MsrA and MsrB are thought to have
      similar roles in oxidative protein repair each targeting a diastereomer of
      methionine sulfoxide, their deletion resulted in different phenotypes. GFP
      fusions of MsrA and MsrB showed different localization patterns and primarily
      localized to cytoplasm and mitochondria, respectively. This finding agreed with
      compartment-specific enrichment of MsrA and MsrB activities. These results show
      that oxidative stress contributes to mitochondrial dysfunction through oxidation
      of methionine residues in proteins located in different cellular compartments.

PMID- 20799726
TI  - Predicting phospholipidosis using machine learning.
AB  - Phospholipidosis is an adverse effect caused by numerous cationic amphiphilic
      drugs and can affect many cell types. It is characterized by the excess
      accumulation of phospholipids and is most reliably identified by electron
      microscopy of cells revealing the presence of lamellar inclusion bodies. The
      development of phospholipidosis can cause a delay in the drug development
      process, and the importance of computational approaches to the problem has been
      well documented. Previous work on predictive methods for phospholipidosis showed
      that state of the art machine learning methods produced the best results. Here we
      extend this work by looking at a larger data set mined from the literature. We
      find that circular fingerprints lead to better models than either E-Dragon
      descriptors or a combination of the two. We also observe very similar performance
      in general between Random Forest and Support Vector Machine models.

PMID- 20799727
TI  - NMR characterization of copper-binding domains 4-6 of ATP7B .
AB  - The Wilson disease protein (ATP7B) is a copper-transporting member of the P-type
      ATPase superfamily, which plays a central role in copper homeostasis and
      interacts with the copper chaperone Atox1. The N-terminus of ATP7B is comprised
      of six copper-binding domains (WCBDs), each capable of binding one copper atom in
      the +1 oxidation state. To better understand the regulatory effect of copper
      binding to these domains, we have performed NMR characterization of WCBD4-6
      (domains 4-6 of ATP7B). (15)N relaxation measurements on the apo and Cu(I)-bound
      WCBD4-6 show that there is no dramatic change in the dynamic properties of this
      three-domain construct; the linker between domains 4 and 5 remains flexible,
      domains 5 and 6 do not form a completely rigid dimer but rather have some
      flexibility with respect to each other, and there is minimal change in the
      relative orientation of the domains in the two states. We also show that,
      contrary to previous reports, the protein-protein interaction between Atox1 and
      the copper-binding domains takes place even in the absence of copper. Comparison
      of apo and Cu(I)-bound spectra of WCBD1-6 shows that binding of Cu(I) does not
      induce the formation of a unit that tumbles as a single entity, consistent with
      our results for WCBD4-6. We propose that copper transfer to and between the N
      terminal domains of the Wilson Cu-ATPase occurs via protein interactions that are
      facilitated by the flexibility of the linkers and the motional freedom of the
      domains with respect to each other.

PMID- 20799728
TI  - Intramolecular conversion of pentaaquahydroperoxidochromium(III) ion to aqueous
      chromium(V): potential source of carcinogenic forms of chromium in aerobic
      organisms.
AB  - The decomposition of the title compound (H(2)O)(5)CrOOH(2+) (hereafter
      Cr(aq)OOH(2+)) in acidic aqueous solutions is kinetically complex and generates
      mixtures of products (Cr(aq)(3+), HCrO(4)(-), H(2)O(2), and O(2)). Relative
      yields of individual products vary greatly with reaction conditions and initial
      concentrations of Cr(aq)OOH(2+). At pH 5.5 in the presence of O(2), the reaction
      was complete in less than a minute and generated chromate in about 70% yield.
      These findings, in addition to poor reproducibility of kinetic data, are
      indicative of the involvement of one or more reactive intermediates that consume
      additional amounts of Cr(aq)OOH(2+) in post-rate-determining steps. The kinetics
      were simplified in the presence of H(2)O(2) or ABTS(2-), both of which are
      capable of scavenging strongly oxidizing intermediates. The measured rate
      constant in 0.10 M HClO(4) at low O(2) concentrations (<=0.03 mM) was independent
      of the concentration of the scavengers and was, within error, the same for ABTS(2
      ), k = 4.9 (+/-0.2) * 10(-4) s(-1), and H(2)O(2), k = 5.3 (+/-0.7) * 10(-4) s(
      1). At a constant ionic strength of 1.0 M, the reaction in the presence of either
      H(2)O(2) or ABTS(2-) obeyed a two-term rate law, k(obs)/s(-1) = 6.7 (+/-0.7) *
      10(-4) + 7.6 (+/-1.1) * 10(-4) [H(+)]. Both in the presence and absence of ABTS(2
      ) as the scavenger, the yields of H(2)O(2) increased with increasing [H(+)].
      These results are discussed in terms of a dual-pathway mechanism for the decay of
      Cr(aq)OOH(2+). The H(+)-catalyzed path leads to the dissociation of H(2)O(2) from
      Cr(III), while in the H(+)-independent reaction, Cr(aq)OOH(2+) is transformed to
      Cr(V). Both scavengers rapidly remove Cr(V) and simplify both the kinetics and
      products.

PMID- 20799729
TI  - Persistence dictates two more R's.

PMID- 20799730
TI  - High-throughput identification of microbial transformation products of organic
      micropollutants.
AB  - During wastewater treatment, many organic micropollutants undergo microbially
      mediated reactions resulting in the formation of transformation products (TPs).
      Little is known on the reaction pathways that govern these transformations or on
      the occurrence of microbial TPs in surface waters. Large sets of
      biotransformation data for organic micropollutants would be useful for assessing
      the exposure potential of these TPs and for enabling the development of structure
      based biotransformation prediction tools. The objective of this work was to
      develop an efficient procedure to allow for high-throughput elucidation of TP
      structures for a broad and diverse set of xenobiotics undergoing microbially
      mediated transformation reactions. Six pharmaceuticals and six pesticides were
      spiked individually into batch reactors seeded with activated sludge. Samples
      from the reactors were separated with HPLC and analyzed by linear ion trap
      orbitrap mass spectrometry. Candidate TPs were preliminarily identified with an
      innovative post-acquisition data processing method based on target and non-target
      screenings of the full-scan MS data. Structures were proposed following
      interpretation of MS spectra and MS/MS fragments. Previously unreported microbial
      TPs were identified for the pharmaceuticals bezafibrate, diazepam, levetiracetam,
      oseltamivir, and valsartan. A variety of previously reported and unreported TPs
      were identified for the pesticides. The results showed that the complementary use
      of the target and non-target screening methods allowed for a more comprehensive
      interpretation of the TPs generated than either would have provided individually.

PMID- 20799732
TI  - Control over interpenetration in lanthanide-organic frameworks: synthetic
      strategy and gas-adsorption properties.
AB  - Two isostructural lanthanide-organic frameworks (1 and 2) with 2-fold
      interpenetrating nets have been synthesized based on 1,4-benzenedicarboxylic acid
      (H(2)BDC). By application of an organic ligand with hindrance groups and a
      terminal chelating ligand to replace BDC and coordinated solvates,
      interpenetration has been effectively controlled. The gas-sorption properties of
      the noninterpenetrating net have been studied.

PMID- 20799731
TI  - Oncogenic CARD11 mutations induce hyperactive signaling by disrupting
      autoinhibition by the PKC-responsive inhibitory domain.
AB  - The regulated activation of NF-kappaB by antigen receptor signaling is required
      for normal B and T lymphocyte activation during the adaptive immune response.
      Dysregulated NF-kappaB activation is associated with several types of lymphoma,
      including diffuse large B cell lymphoma (DLBCL). During normal antigen receptor
      signaling, the multidomain scaffold protein CARD11 undergoes a transition from a
      closed, inactive state to an open, active conformation that recruits several
      signaling proteins into a complex, leading to IKK kinase activation. This
      transition is regulated by the CARD11 inhibitory domain (ID), which participates
      in intramolecular interactions that prevent cofactor binding to CARD11 prior to
      signaling, but which is neutralized after receptor engagement by phosphorylation.
      Several oncogenic CARD11 mutations have been identified in DLBCL that enhance
      activity and that are mostly found in the coiled-coil domain. However, the
      mechanisms by which these mutations cause CARD11 hyperactivity and spontaneous NF
      kappaB activation are poorly understood. In this report, we provide several lines
      of evidence that oncogenic mutations F123I and L225LI induce CARD11 hyperactivity
      by disrupting autoinhibition by the CARD11 ID. These mutations disrupt ID
      mediated intramolecular interactions and ID-dependent inhibition and bypass the
      requirement for ID phosphorylation during T cell receptor signaling.
      Intriguingly, these mutations selectively enhance the apparent affinity of CARD11
      for Bcl10, but not for other signaling proteins that are recruited to CARD11 in
      an ID-dependent manner during normal antigen receptor signaling. Our results
      establish a mechanism that explains how DLBCL-associated mutations in CARD11 can
      initiate spontaneous, receptor-independent activation of NF-kappaB.

PMID- 20799733
TI  - Isomerism with metallacalix[4]arenes of the nonsymmetrical pyrimidine nucleobase
      cytosine: how connectivity and rotamer state determine the topology of
      multinuclear derivatives.
AB  - Two cyclic octanuclear complexes, 2 and 3, of cation composition
      [{Pd(bpy)}(8)C(4)](8+) (bpy = 2,2'-bipyridine) form side by side when
      [Pd(bpy)(H(2)O)(2)](2+) and cytosine (H(2)C) are reacted in water. The two
      complexes are isomers, composed of central metallacalix[4]arene backbones to
      which four additional Pd(bpy) units are bonded pairwise to exocyclic groups of
      the C(2-) ligands. As a consequence of differences in the N1-N3 connectivity
      patterns of the two central Pd(4)C(4) rings and 1,3-alternate rotamer states of
      cytosinate in both compounds, the spatial arrangements of exocyclic groups are
      distinctly different, leading to two Pd(3) stacks and two Pd(1) entities in 2,
      yet to four Pd(2) stacks in 3.

PMID- 20799734
TI  - Torsionally controlled electronic coupling in mixed-valence oxodimolybdenum
      nitrosyl scorpionates--a DFT study.
AB  - The density functional theory (DFT) method has been used to study the electronic
      communication in strongly interacting oxo-bridged di-{Mo(II,I)(NO(+))}(3+,2+)
      complexes stabilized by tris(3-methylpyrazol-1-yl)borate, [Tp(Me)](-) (dihydroxy
      1' and its modified analogs), having fully localized valences on the two Mo
      centers (Class I), despite a short (ca. 3.8 A) Mo...Mo distance. Structural and
      electrochemical (separation between the redox potentials Delta(red/ox)E(1/2))
      properties and IR spectra (in particular the nu(NO) frequencies) obtained from
      the B3LYP calculations for 1' are successfully related to experimental values.
      Strongly twisted geometry with the (O)N-Mo1...Mo2-N(O) angle close to 90 degrees
      (confirmed by DFT modeling performed for 1'(-1,0,+1) and X-ray diffraction study
      of [{Mo(NO)(Tp(Me2))(OH)}(2)(mu-O)](-) (1) presented herein) is a common, though
      so far not fully understood, structural feature of this class of mu-oxo species,
      in contrast to the closely related {Mo(V)(=O)}(3+) analogs. This study shows that
      the orthogonality of the local equatorial planes for the two Mo centers may be
      rationalized by the electronic structure, namely from the balance between the
      destabilizing repulsion of the Mo-based (d, pi(x)*)(b) electron pairs versus a
      favorable but relatively weak electron delocalization. Strongly repelling
      electron pairs avoid each other, which enforces the twisted geometries and blocks
      the electron delocalization. Steric hindrance (a nonbonding repulsion of the
      adjacent Tp(x) ligands and the weak hydrogen-bonding interactions, i.e., OH...ON,
      OH...OH, and C-H...O((NO/OH))) is shown not to be decisive since neither the
      removal of the inner 3-Me groups of [Tp(Me)](-) in complex 1' nor the
      substitution of OH groups by OCH(3) ligands did substantially influence the
      dihedral twist angle in the minimum energy structure. Yet the relative
      orientation of the {Mo(NO)}(2+,3+) cores along with the position of the bridging
      oxygen (significantly bent upon reduction) controls the prospective
      intramolecular through-bond electron transfer in the mixed valence form. Our DFT
      modeling demonstrates that a maximum delocalization (via a hole-transfer
      mechanism) of the unpaired electron in 1'(-), measured as a spin population on
      the nonreduced Mo2 center, is achieved for the structure with a torsional
      deflection of 23 degrees, at a cost of 16.5 kcal/mol. These results show that the
      electron exchange along the Mo-O-Mo array in the originally fully valence-trapped
      {17e:16e}(-) complexes may be controlled and can be thermally activated (e.g.,
      using a high-boiling solvent or by irradiation at ca. 50-200 cm(-1)).

PMID- 20799735
TI  - Porous coordination polymers of transition metal sulfides with PtS topology built
      on a semirigid tetrahedral linker.
AB  - Four novel porous metal sulfide coordination polymers, [M(tpom)S(x)(SH)(y)] x
      z(H(2)O) (metal-sulfide frameworks, denoted MSF-n, n = 1, Cd; 2, Mn; 3, Fe; 4,
      Co; x = 0, y = 2 for 1, 2, and 4 and x = 0.54, y = 1.46 for 3), were
      solvothermally prepared by using a quadridentate linker, tetrakis(4
      pyridyloxymethylene)methane (tpom), in the presence of organic sulfur compound
      under an acidic conditions. MSF-n (n = 1-4) is isostructural and built upon the
      tetrahedral tpom linker and square planar MS(x)(SH)(y) unit, which form a binodal
      4,4-connected porous framework with a 2-fold interpenetrated 4(2)8(4)-pts net.
      With rectangular pore channels of about 5 x 6 A(2) (interatomic distances between
      the nearest protruding H atoms across) running along both the crystallographic a
      and b directions, MSF-n possesses permanent porosity with a BET surface area of
      575, 622, 617, and 767 m(2)/g for MSF-1, -2, -3, and -4, respectively, as
      estimated from N(2) adsorption measurements. MSF-n (n = 1-4) has hydrogen storage
      capacities of 1.03, 1.37, 1.29, and 1.58 wt % at 77 K and 1 atm, respectively,
      each corresponding to 2.0 H(2) molecules per unit cell. In addition, MSF-n (n = 1
      4) can adsorb 24.1, 25.0, 21.6, and 24.1 wt % of carbon dioxide and 6.0, 6.1,
      5.6, and 6.4 wt % of methane, respectively, at room temperature and 20 atm.

PMID- 20799736
TI  - Probing the structure, conformation, and stereochemical exchange in a family of
      lanthanide complexes derived from tetrapyridyl-appended cyclen.
AB  - A series of lanthanide complexes have been synthesized from 1,4,7,10-tetrakis(2
      pyridylmethyl)-1,4,7,10-tetraazacyclododecane. Crystallographic studies indicate
      that, in the solid phase, all of the lanthanide ions are 9-coordinate and are
      bound to eight N atoms from the donor ligand, with the ninth site being filled by
      a counterion or solvent molecule. In solution, time-resolved luminescence studies
      indicate that the luminescence exhibits contributions from two species
      corresponding to the nonhydrated and hydrated forms. The NMR spectra in protic
      media show the presence of two dominant isomers on the NMR time scale;
      furthermore, the spectra are very different from those obtained for 1,4,7,10
      tetraazacyclododecane-N',N'',N''',N''''-tetraacetic acid (DOTA) and its
      derivatives. The different forms of the complex undergo slow conformational and
      enantiomeric exchange in solution, which has been measured by NMR. The exchange
      path has been mapped out by density functional theory calculations and shows
      multiple metastable conformations (with respect to the dihedral angles of the
      cyclen ring). This contrasts with the established NMR behavior of DOTA complexes,
      which has been described by a two-state solution equilibrium.

PMID- 20799737
TI  - X-ray structural characterization of the bis-guanine derivative of a cisplatin
      analogue having just one proton on each coordinated nitrogen and a head-to-head
      conformation: [Pt{(+/-)-N,N'-dimethyl-2,3-diaminobutane}(9-ethyl
      guanine)2]dinitrate.
AB  - The X-ray structural and NMR characterization of a bis-guanine derivative of a
      cisplatin analogue designed to reduce the rate of the Pt-N7 rotation of the
      coordinated guanine nucleobases by more than 1-million-fold is reported. The
      [Pt{(+/-)-Me(2)dab}(9-EtG)(2)](NO(3))(2) (Me(2)dab = N,N'-dimethyl-2,3
      diaminobutane, 9-EtG = 9-ethyl-guanine) complex crystallizes in the P2(1)/n space
      group, and the crystal contains a racemic mixture of complex molecules. The data
      were collected at 120 +/- 2 K, and the crystal and molecular structure
      (comprising one disordered nitrate) were resolved and refined to conventional
      agreement factors of R1 = 0.0270 and wR2 = 0.0565. The guanine ligands assume the
      less common head-to-head (HH) orientation, disclosing full details of the
      intramolecular relationships between cis guanines and between guanine and cis
      amine. Moreover, an understanding has been gained of the steric factors
      determining induction of asymmetry (from carbons to adjacent nitrogen atoms) and
      puckering of the chelate ring (delta or lambda for R,S,S,R or S,R,R,S
      configurations at the N,C,C,N chelate-ring atoms, respectively) within the
      Me(2)dab ligand. The chemical shift separation between H8 signals of the two HT
      atropisomers and between the two H8 signals of the single HH atropisomer can be
      explained in terms of canting of the nucleobases relative to the coordination
      plane and in terms of the different relationships between the H8 proton of one
      guanine and the shielding zone of the cis guanine. Furthermore, for each
      configuration of the Me(2)dab ligand (R,S,S,R or S,R,R,S), the NMR data indicate
      that the handedness of canting is similar for the two guanines in all three (two
      HT and one HH) conformers (R canting for R,S,S,R and L canting for S,R,R,S
      configuration).

PMID- 20799738
TI  - Synthesis of diamidopyrrolyl molybdenum complexes relevant to reduction of
      dinitrogen to ammonia.
AB  - A potentially useful trianionic ligand for the reduction of dinitrogen
      catalytically by molybdenum complexes is one in which one of the arms in a
      [(RNCH(2)CH(2))(3)N](3-) ligand is replaced by a 2-mesitylpyrrolyl-alpha-methyl
      arm, that is, [(RNCH(2)CH(2))(2)NCH(2)(2-MesitylPyrrolyl)](3-) (R = C(6)F(5), 3,5
      Me(2)C(6)H(3), or 3,5-t-Bu(2)C(6)H(3)). Compounds have been prepared that contain
      the ligand in which R = C(6)F(5) ([C(6)F(5)N)(2)Pyr](3-)); they include
      [(C(6)F(5)N)(2)Pyr]Mo(NMe(2)), [(C(6)F(5)N)(2)Pyr]MoCl, [(C(6)F(5)N)(2)Pyr]MoOTf,
      and [(C(6)F(5)N)(2)Pyr]MoN. Compounds that contain the ligand in which R = 3,5-t
      Bu(2)C(6)H(3) ([Ar(t-Bu)N)(2)Pyr](3-)) include {[(Ar(t-Bu)N)(2)Pyr]Mo(N(2))}Na(15
      crown-5), {[(Ar(t-Bu)N)(2)Pyr]Mo(N(2))}[NBu(4)], [(Ar(t-Bu)N)(2)Pyr]Mo(N(2))
      (nu(NN) = 2012 cm(-1) in C(6)D(6)), {[(Ar(t-Bu)N)(2)Pyr]Mo(NH(3))}BPh(4), and
      [(Ar(t-Bu)N)(2)Pyr]Mo(CO). X-ray studies are reported for
      [(C(6)F(5)N)(2)Pyr]Mo(NMe(2)), [(C(6)F(5)N)(2)Pyr]MoCl, and [(Ar(t
      Bu)N)(2)Pyr]MoN. The [(Ar(t-Bu)N)(2)Pyr]Mo(N(2))(0/-) reversible couple is found
      at -1.96 V (in PhF versus Cp(2)Fe(+/0)), but the [(Ar(t-Bu)N)(2)Pyr]Mo(N(2))(+/0)
      couple is irreversible. Reduction of {[(Ar(t-Bu)N)(2)Pyr]Mo(NH(3))}BPh(4) under
      Ar at approximately -1.68 V at a scan rate of 900 mV/s is not reversible. Ammonia
      in [(Ar(t-Bu)N)(2)Pyr]Mo(NH(3)) can be substituted for dinitrogen in about 2 h if
      10 equiv of BPh(3) are present to trap the ammonia that is released. [(Ar(t
      Bu)N)(2)Pyr]Mo-N=NH is a key intermediate in the proposed catalytic reduction of
      dinitrogen that could not be prepared. Dinitrogen exchange studies in [(Ar(t
      Bu)N)(2)Pyr]Mo(N(2)) suggest that steric hindrance by the ligand may be
      insufficient to protect decomposition of [(Ar(t-Bu)N)(2)Pyr]Mo-N=NH through a
      variety of pathways. Three attempts to reduce dinitrogen catalytically with
      [(Ar(t-Bu)N)(2)Pyr]Mo(N) as a "catalyst" yielded an average of 1.02 +/- 0.12
      equiv of NH(3).

PMID- 20799739
TI  - Synthesis, structure, and solid-state transformation studies of phosphonoacetate
      based hybrid compounds of uranium and thorium.
AB  - Three new phosphonoacetate hybrid frameworks based on the actinide elements
      uranium and thorium have been synthesized. The compounds
      [C(4)N(2)H(14)][(UO(2))(2)(O(3)PCH(2)COO)(2)] x H(2)O, I,
      [C(4)N(2)H(14)][(UO(2))(2)(C(2)O(4))(O(3)PCH(2)COOH)(2)], II, and
      Th(H(2)O)(2)(O(3)PCH(2)COO)(C(2)O(4))(0.5) x H(2)O, III, are built up from the
      connectivity between the metal polyhedra and the phosphonoacetate/oxalate units.
      Compound II has been prepared using a solvent-free approach, by a solid state
      reaction at 150 degrees C. It has been shown that II can also be prepared through
      a room temperature mechanochemical (grinding) route. The layer arrangement in III
      closely resembles to that observed in I. The compounds have been characterized by
      powder X-ray diffraction, IR spectroscopy, thermogravimetric analysis, and
      fluorescence studies.

PMID- 20799740
TI  - Structural and magnetic effects of meso-substitution in alkyl-substituted
      metalloporphyrinate pi-cation radicals: characterization of
      [Fe(TalkylP*)(Cl)]SbCl6 (alkyl = ethyl and n-propyl).
AB  - We report the preparation and characterization of two meso-alkyl substituted
      porphyrin pi-cation radical derivatives, [Fe(TalkylP(*))(Cl)]SbCl(6) (alkyl =
      ethyl or propyl). Both complexes have been characterized by UV/vis/near-IR, IR,
      and Mossbauer spectroscopy, temperature-dependent solid-state magnetic
      susceptibility measurements, and X-ray structure determinations. All data for
      both oxidized species are consistent with the formulation of the complexes as
      ring-oxidized iron(III) porphyrin species. The molecular structures of the two
      five-coordinate species have the typical square-pyramidal coordination group of
      high-spin iron(III) derivatives. The crystal structures also reveal that the
      species form cofacial pi-pi dimers with lateral shifts of 1.44 A and 3.22 A,
      respectively, for the propyl and ethyl radical derivatives. Both radicals exhibit
      porphyrin cores with alternating bond distance patterns in the inner 16-membered
      ring. In addition, [Fe(TEtP(*))(Cl)]SbCl(6) and [Fe(TPrP(*))(Cl)]SbCl(6) have
      been characterized by temperature-dependent (6-300 K) magnetic susceptibility
      studies, the best fitting of the temperature-dependent moments reveal strong
      coupling between iron spins and porphyrin radical, and a smaller magnitude of
      antiferromagnetic coupling between ring radicals, which are opposite to those
      found in the five-coordinate iron(III) OEP radicals. The differences in structure
      and properties of the cation radical meso-alkyl and beta-alkyl derivatives
      possibly reflect differences in properties of a(1u)- and a(2u)-forming radicals.

PMID- 20799741
TI  - 2-(Aminomethyl)phenyl complexes of Au(III), mixed Au(III)/Ag(I), and Pd(II) with
      the 2,2-diacetyl-1,1-ethylenedithiolato ligand: dancing of palladacycles around a
      juggler ligand.
AB  - The reaction of [Tl(2){mu-S,S-S(2)C=C{C(O)Me}(2)}] with [Au(C,N
      C(6)H(4)CH(2)NMe(2)-2)Cl(2)] (1:1) gives [{Au(C,N-C(6)H(4)CH(2)NMe(2)-2)}{S,S
      S(2)C=C{C(O)Me}(2)}] (1) which, in turn, reacts with AgClO(4) (1:1) to give
      [{Au(C,N-C(6)H(4)CH(2)NMe(2)-2)}{Ag(OClO(3))}{S(2)C=C{C(O)Me}(2)}] (2). Complexes
      [{Au(C,N-C(6)H(4)CH(2)NMe(2)-2)}{Ag(X)(PPh(3))}{S(2)C=C{C(O)Me}(2)}] [X = OClO(3)
      (3), ONO(2) (4)] have been obtained by reaction of 1 with PPh(3) and AgClO(4) or
      AgNO(3), respectively (1:1:1). Complex 3 can also be obtained by reacting 2 with
      PPh(3) (1:1). Complexes [Pd(C,N-C(6)H(4)CH(2)NR(2)-2)(mu-Cl)](2) (R = Me, H)
      react (i) with [Tl(2){S(2)C=C{C(O)Me}(2)}] and [PPN]Cl (0.5:1:1, PPN =
      Ph(3)P=N=PPh(3)) to form PPN[Pd(C,N-C(6)H(4)CH(2)NR(2)-2){S,S
      S(2)C=C{C(O)Me}(2)}] [R = H (5a), Me (5b)], or (ii) with
      [Tl(2){S(2)C=C{C(O)Me}(2)}] (1:1) to form [{Pd(C,N-C(6)H(4)CH(2)NR(2)-2)}(2){mu
      S,S,O-S(2)C=C{C(O)Me}(2)}] [R = H (6a), Me (6b)]. The trinuclear complexes
      [{Pd(C,N-C(6)H(4)CH(2)NR(2)-2)}(3){mu(3)-O,S,S,O-S(2)C=C{C(O)Me}(2)}]ClO(4) [R =
      H (7a), Me (7b)] can be prepared by reacting the corresponding dinuclear complex
      6a or 6b with [Pd(C,N-C(6)H(4)CH(2)NR(2)-2)(NCMe)(2)]ClO(4) (1:1). The crystal
      structures of 1, 6b x CH(2)Cl(2), and 7b x CH(2)Cl(2) have been determined. NMR
      studies have been carried out to explain the solution behavior of these
      complexes. VT-NMR and line shape analysis for the species where R = Me (5b, 6b,
      7b) have allowed the estimation of the activation parameters for these exchange
      processes.

PMID- 20799742
TI  - Formation of uranium(IV) oxide clusters from uranocene [U(eta(8)-C8H8)2] and
      uranyl [UO2X2] compounds.
AB  - Uranocene [U(eta(8)-C(8)H(8))(2)] reacted in refluxing pyridine with 2 equiv of
      the uranyl(VI) compound [UO(2)(OTf)(2)] or [UO(2)I(2)(THF)(3)] (OTf = O(3)SCF(3);
      THF = tetrahydrofuran) or 1 equiv of the uranyl(V) complex
      [UO(2)(py)(2.3)K(OTf)(2)] to afford the hexanuclear uranium(IV) oxide cluster
      [U(6)O(8)(OTf)(8)(py)(8)] (1) or [U(6)O(8)I(8)(py)(10)] (3). Complexes 1 and 3
      were easily isolated in good yield because they were deposited as
      microcrystalline powders with the release of free cyclooctatetraene as a unique
      byproduct. A similar reaction in THF gave [U(6)O(8)(OTf)(8)(THF)(8)] (2), whose
      isolation was impeded by polymerization of the solvent. With complexes [U(eta(8)
      C(8)H(8))(2)] and [UO(2)(OTf)(2)] in a molar ratio of 4:3 or in the presence of
      excess uranocene, only crystals of the mono(eta(8)-C(8)H(8)) aggregate
      [U(6)O(8)(eta(8)-C(8)H(8))(OTf)(6)(py)(8)] (4) were obtained. The crystal
      structures of 1 x 2 py, 2 x 2 THF, 3 x py, and 4 x py were determined. Whereas
      uranocene and uranyl(VI) compounds are generally viewed as the most robust
      uranium compounds, they were found to fuse together into hexanuclear assemblages.
      These studies revealed the unusual four-electron reductive capacity of a
      uranium(IV) complex, in particular uranocene, which, through the loss of its two
      C(8)H(8) ligands, induces the activation and reduction of the strong U=O bonds of
      the uranyl moiety.

PMID- 20799744
TI  - Acoustic-wave-induced analyte separation in narrow fluidic confinements in the
      presence of interfacial interactions.
AB  - In the present work, we attempt to analyze the influences of acoustic forces, in
      conjunction with the intrinsic electrokinetic effects as well as the near-wall
      attractive and repulsive forces, on the transport and size-based separation of
      charged analytes in a background-pressure-driven flow through a narrow fluidic
      confinement. By executing a regular perturbation analysis, we establish that the
      speed of traverse and the extent of spreading (dispersion) of the analyte bands
      is effectively determined by the ratio of particle to channel heights, channel
      height relative to the Debye length, and all other significant acoustic and
      nonacoustic parameters. These factors in tandem may dictate the analyte
      separation characteristics (quantified by the resolution of separation), in tune
      with the particular harmonic of the acoustic wave, the strengths of the induced
      electrical double layer fields, and the van der Waals interaction mechanisms. We
      quantitatively pinpoint the relationship between the harmonics to be employed and
      particle sizes to be separated. Our study reveals that there is a critical
      channel height beyond which the acoustic effects may effectively mask the near
      wall interactions and below which the transverse migrative influences induced by
      the walls may influence the separation characteristics in a rather profound
      manner. The results implicate an interesting high-efficiency separation regime
      that can be obtained with a judicious combination of the background flow, energy
      intensity of the acoustic effects, and induced electrical double layer
      interactions.

PMID- 20799745
TI  - Adsorption of beta-adrenergic agonists used in sport doping on metal
      nanoparticles: a detection study based on surface-enhanced Raman scattering.
AB  - The adsorption of beta(2)-adrenergic agonist (betaAA) drugs clenbuterol,
      salbutamol, and terbutaline on metal surfaces has been investigated in this work
      by means of surface-enhanced Raman scattering (SERS). To assist in this
      investigation, a previous vibrational (IR and normal Raman) characterization of
      these drugs was performed, supported by ab initio density functional theory
      calculations. The application of SERS was aimed to apply this highly sensitive
      technique, based on localized surface plasmon resonance, in the detection of
      betaAA at trace concentrations and as a possible alternative method which can be
      postulated in routine antidoping analysis. The adsorption of these drugs was
      studied in depth at different experimental conditions: on Au and Ag, at different
      pHs, and with varying adsorbate concentration. Moreover, plasmon resonance
      spectroscopy was employed to investigate the adsorption of these drugs on the
      metal nanoparticles as well as their aggregation. It was found that the
      adsorption of these molecules is more effective on gold nanoparticles and at
      acidic pH, based on the direct interaction of the aromatic or aliphatic moieties
      through ionic or coordination bonds with the metal. These drugs followed a
      Langmuir adsorption model from which the adsorption constant and the limit of
      detection can be determined.

PMID- 20799743
TI  - Development and application of an LC-MS/MS method for the detection of the vinyl
      chloride-induced DNA adduct N(2),3-ethenoguanine in tissues of adult and weanling
      rats following exposure to [(13)C(2)]-VC.
AB  - In the 1970s, exposure to vinyl chloride (VC) was shown to cause liver
      angiosarcoma in VC workers. We have developed a new LC-MS/MS method for analyzing
      the promutagenic DNA adduct N(2),3-ethenoguanine (epsilonG) and have applied this
      to DNA from tissues of both adult and weanling rats exposed to 1100 ppm
      [(13)C(2)]-VC for 5 days or 1100 ppm VC for 1 day. This assay utilizes neutral
      thermal hydrolysis and an HPLC cleanup prior to quantitation by LC-MS/MS. The
      number of endogenous and exogenous epsilonG adducts in DNA from tissues of adult
      rats exposed to [(13)C(2)]-VC for 5 days was 4.1 +/- 2.8 adducts/10(8) guanine of
      endogenous and 19.0 +/- 4.9 adducts/10(8) guanine of exogenous epsilonG in the
      liver, 8.4 +/- 2.8 adducts/10(8) guanine of endogenous and 7.4 +/- 0.5
      adducts/10(8) guanine of exogenous epsilonG in the lung, and 5.9 +/- 3.3
      adducts/10(8) guanine of endogenous and 5.7 +/- 2.1 adducts/10(8) guanine of
      exogenous epsilonG in the kidney (n = 4). Additionally, the data from weanling
      rats demonstrated higher numbers of exogenous epsilonG, with ~4-fold higher
      amounts in the liver DNA of weanlings (75.9 +/- 17.9 adducts/10(8) guanine) in
      comparison to adult rats and ~2-fold higher amounts in the lung (15.8 +/- 3.6
      adducts/10(8) guanine) and kidney (12.9 +/- 0.4 adducts/10(8) guanine) (n = 8).
      The use of stable isotope labeled VC permitted accurate estimates of the half
      life of epsilonG for the first time by comparing [(13)C(2)]-epsilonG in adult
      rats with identically exposed animals euthanized 2, 4, or 8 weeks later. The half
      life of epsilonG was found to be 150 days in the liver and lung and 75 days in
      the kidney, suggesting little or no active repair of this promutagenic adduct.

PMID- 20799746
TI  - Separating DNA with different topologies by atomic force microscopy in comparison
      with gel electrophoresis.
AB  - Atomic force microscopy, which is normally used for DNA imaging to gain
      qualitative results, can also be used for quantitative DNA research, at a single
      molecular level. Here, we evaluate the performance of AFM imaging specifically
      for quantifying supercoiled and relaxed plasmid DNA fractions within a mixture,
      and compare the results with the bulk material analysis method, gel
      electrophoresis. The advantages and shortcomings of both methods are discussed in
      detail. Gel electrophoresis is a quick and well-established quantification
      method. However, it requires a large amount of DNA, and needs to be carefully
      calibrated for even slightly different experimental conditions for accurate
      quantification. AFM imaging is accurate, in that single DNA molecules in
      different conformations can be seen and counted. When used carefully with
      necessary correction, both methods provide consistent results. Thus, AFM imaging
      can be used for DNA quantification, as an alternative to gel electrophoresis.

PMID- 20799748
TI  - Study of MoVO(y) (y = 2-5) anion and neutral clusters using anion photoelectron
      spectroscopy and density functional theory calculations.
AB  - The vibrationally resolved anion photoelectron (PE) spectra of MoVO(y)(-) (y = 2 
      5) metal suboxide clusters are presented and analyzed in the context of density
      functional theory (DFT) calculations. The electronically congested spectra
      reflect an increase in cluster electron affinity with increasing oxidation state.
      Ion beam hole-burning results reveal the features in the PE spectra of MoVO(2)(-)
      and MoVO(4)(-) are a result of only one anion isomer, while at least two isomers
      contribute to electronic structure observed in the PE spectrum of MoVO(3)(-).
      Spectral features of the binary systems are compared to their pure analogs,
      Mo(2)O(y) and V(2)O(y). An attempt to characterize the anion and neutral
      electronic and molecular structures is made by comparison with results from DFT
      calculations. However, reconciliation between the cluster spectra and the
      calculated spectroscopic parameters is not as straightforward as in previous
      studies on similar systems (Yoder, B. L.; Maze, J. T.; Raghavachari, K.; Jarrold,
      C. C. J. Chem. Phys. 2005, 122, 094313 and Mayhall, N. J.; Rothgeb, D. W.;
      Hossain, E.; Raghavachari, K.; Jarrold, C. C. J. Chem. Phys. 2009, 130, 124313).

PMID- 20799747
TI  - ExbB protein in the cytoplasmic membrane of Escherichia coli forms a stable
      oligomer.
AB  - In Gram-negative bacteria like Escherichia coli the ExbB-ExbD-TonB protein
      complex is anchored to the cytoplasmic membrane and is involved in energization
      of outer membrane transport. Outer membrane proteins catalyze energy-coupled
      transport of scarce nutrients. Energy is derived from the protonmotive force of
      the cytoplasmic membrane which is transferred through ExbB-ExbD-TonB to the outer
      membrane transporters. Earlier studies showed that ExbB is the most abundant
      protein of the ExbB-ExbD-TonB complex and stabilizes TonB and ExbD. To advance
      understanding of the role of ExbB in the membrane organization of the ExbB-ExbD
      TonB complex, His-tagged ExbB was solubilized with decyl maltoside and purified
      to electrophoretic homogeneity. Its size and shape were determined by blue native
      gel electrophoresis, size exclusion chromatography, transmission electron
      microscopy, and small-angle X-ray scattering. Decyl maltoside bound to ExbB was
      quantified by the anthrone method that determines the sugar moiety of decyl
      maltoside. The results obtained with the four methods consistently indicated that
      isolated ExbB adopts a stable homooligomer with four to six monomers. We propose
      that the ExbB homooligomer forms a platform on which ExbD and TonB are assembled
      to form the energy-transducing complex in the cytoplasmic membrane.

PMID- 20799749
TI  - FTIR spectroscopy studies on the bioprotective effectiveness of trehalose on
      human hemoglobin aqueous solutions under 50 Hz electromagnetic field exposure.
AB  - The effects of extremely low frequency electromagnetic field on the protein
      structure of hemoglobin were investigated by means of Fourier transform infrared
      spectroscopy. Three samples of different hemoglobin aqueous solutions (also in
      the presence of sucrose and trehalose) were exposed to a 50 Hz electromagnetic
      field at 1 mT, and FTIR measurements were performed after 3 h of exposure.
      Quantitative spectral analysis revealed an evident decrease in amide A band
      intensity for hemoglobin in bidistilled water and sucrose aqueous solutions, but
      not for hemoglobin in trehalose aqueous solution. In addition a low relative
      increase of beta-sheet in amide I region was detected for hemoglobin in both
      bidistilled water and sucrose aqueous solutions, whereas no appreciable changes
      were evidenced in the infrared spectra of hemoglobin in trehalose aqueous
      solutions. These results led us to conclude that a 50 Hz electromagnetic field
      can affect the N-H plane bending and C-N stretching vibrations of peptide
      linkages, suggesting compensatory mechanisms by means of environmental
      biochemical agents, such as evidenced by a protective effect of trehalose toward
      a low-frequency electromagnetic field.

PMID- 20799750
TI  - Patterning of peptide nucleic acids using reactive microcontact printing.
AB  - PNAs (peptide nucleic acids) have been immobilized onto surfaces in a fast,
      accurate way by employing reactive microcontact printing. Surfaces have been
      first modified with aldehyde groups to react with the amino end of the
      synthesized PNAs. When patterning fluorescein-labeled PNAs by reactive
      microcontact printing using oxygen-oxidized polydimethylsiloxane stamps,
      homogeneous arrays were fabricated and characterized using optical methods. PNA
      patterned surfaces were hybridized with complementary and mismatched dye-labeled
      oligonucleotides to test their ability to recognize DNA sequences. The stability
      and selectivity of the PNA-DNA duplexes on surfaces have been verified by
      fluorescence microscopy, and the melting curves have been recorded. Finally, the
      technique has been applied to the fabrication of chips by spotting a PNA
      microarray onto a flat PDMS stamp and reproducing the same features onto many
      slides. The chips were finally applied to single nucleotide polymorphism
      detection on oligonucleotides.

PMID- 20799751
TI  - Effects of coupled homogeneous chemical reactions on the response of large
      amplitude AC voltammetry: extraction of kinetic and mechanistic information by
      Fourier transform analysis of higher harmonic data.
AB  - Large-amplitude ac voltammograms contain a wealth of kinetic information
      concerning electrode processes and can provide unique mechanistic insights
      compared to other techniques. This paper describes the effects homogeneous
      chemical processes have on ac voltammetry in general and provides experimental
      examples using two well-known chemical systems: one simple and one complex.
      Oxidation of [Cp*Fe(CO)(2)](2) (Cp* = eta(5)-pentamethylcyclopentadienyl) in
      noncoordinating media is a reversible one-electron process; in the presence of
      nucleophiles, however, the resulting ligand-induced disproportionation changes
      the process to a multiple step regeneration. The chemical kinetic parameters of
      the regeneration mechanism were discerned via analysis of the third and higher
      harmonics of Fourier-transformed ac voltammetry data. Comparison of experimental
      data to digital simulations provides clear evidence that the reaction proceeds
      via a rapid pre-equilibrium between the electrogenerated monocation and the
      coordinating ligand; simultaneous fitting of the first nine harmonics indicates
      that k(f) = 7500 M(-1) s(-1) and k(r) = 100 s(-1), and that the unimolecular
      decomposition of the corresponding intermediate occurs with a rate constant of
      2.2 s(-1). The rapid cis(+) -> trans(+) isomerization of the electrogenerated cis
      [W(CO)(2)(dpe)(2)](+), where dpe = 1,2-diphenylphosphinoethane, was examined to
      illustrate the effects of a simpler EC mechanism on the higher harmonics; a rate
      constant of 280 s(-1) was determined. These results not only shed new light on
      the chemistry of these systems, but provide a clear demonstration that the higher
      harmonics of ac voltammetry provide mechanistic insights into coupled homogeneous
      processes far more detailed than those that are readily accessible with dc
      techniques.

PMID- 20799752
TI  - Kinetic pathway of antimicrobial peptide magainin 2-induced pore formation in
      lipid membranes.
AB  - The pore formation in lipid membranes induced by the antimicrobial peptide
      magainin 2 is considered to be the main cause for its bactericidal activity. To
      reveal the mechanism of the pore formation, it is important to elucidate the
      kinetic pathway of magainin 2-induced pore formation in lipid membranes. In this
      report, to examine the change in pore size over time during pore formation which
      can monitor its kinetic pathway, we investigated the rate of the leakage of
      various sized fluorescent probes through the magainin 2-induced pores in single
      giant unilamellar vesicles (GUVs) of 50% dioleoylphosphatidylglycerol (DOPG)/50%
      dioleoylphosphatidylcholine (DOPC) membrane. Magainin 2- induced leakage of Texas
      Red dextran 10,000, Texas-Red dextran 3000, and Alexa-Fluor trypsin inhibitor
      occurred in two stages; a transient rapid leakage in the initial stage followed
      by a stage of slow leakage. In contrast, magainin 2 induced a transient, but very
      small (10-20%), leakage of fluorescent probes of a larger size such as Texas-Red
      dextran 40,000 and FITC-BSA. These results indicate that magainin 2 molecules
      initially induce a large, transient pore in lipid membranes following which the
      radius of the pore decreases to a stable smaller size. We estimated the radius of
      these pores, which increases with an increase in magainin 2 concentration. On the
      basis of these data, we propose a hypothesis on the mechanism of magainin 2
      induced pore formation.

PMID- 20799753
TI  - Studies of single aerosol particles containing malonic acid, glutaric acid, and
      their mixtures with sodium chloride. II. Liquid-state vapor pressures of the
      acids.
AB  - The vapor pressures of two dicarboxylic acids, malonic acid and glutaric acid,
      are determined by the measurement of the evaporation rate of the dicarboxylic
      acids from single levitated particles. Two laboratory methods were used to
      isolate single particles, an electrodynamic balance and optical tweezers
      (glutaric acid only). The declining sizes of individual aerosol particles over
      time were followed using elastic Mie scattering or cavity enhanced Raman
      scattering. Experiments were conducted over the temperature range of 280-304 K
      and a range of relative humidities. The subcooled liquid vapor pressures of
      malonic and glutaric acid at 298.15 K were found to be 6.7(-1.2)(+2.6) x 10(-4)
      and 11.2(-4.7)(+9.6) x 10(-4) Pa, respectively, and the standard enthalpies of
      vaporization were respectively 141.9 +/- 19.9 and 100.8 +/- 23.9 kJ mol(-1). The
      vapor pressures of both glutaric acid and malonic acid in single particles
      composed of mixed inorganic/organic composition were found to be independent of
      salt concentration within the uncertainty of the measurements. Results are
      compared with previous laboratory determinations and theoretical predictions.

PMID- 20799754
TI  - Photoluminescence of 2,7-poly(9,9-dialkylfluorene-co-fluorenone) nanoparticles:
      effect of particle size and inert polymer addition.
AB  - Stable nanoparticle dispersions of 2,7-poly(9,9-dialkylfluorene-co-fluorenone)
      (PFFO) and of PFFO/cellulose acetate butyrate (CAB) mixtures with particle size
      ranging between 5 and 500 nm were prepared by miniemulsification in the presence
      of a cationic surfactant. Photoluminescence spectra of nanoparticle dispersions
      showed that the decrease of particle size and of the PFFO/CAB mass ratio induced
      the progressive suppression of the PFFO excimer emission band at 535 nm. This
      behavior was associated with the limited ordered structure and pi-stacking
      arrangement of PFFO molecules when confined within nanoparticles smaller than 150
      nm or in the presence of CAB molecules. All nanoparticle dispersions displayed
      high dimensional stability; however, the relative intensity of the excimer
      emission band increased upon aging reflecting excimer formation due to the high
      mobility of PFFO chains (T(g) -20  degrees C) or fluorene moiety oxidation.

PMID- 20799755
TI  - A new method for examining the cost savings of reducing COPD exacerbations.
AB  - BACKGROUND: Some treatments for chronic obstructive pulmonary disease (COPD) can
      reduce exacerbations, and thus could have a favourable impact on overall
      healthcare costs. OBJECTIVE: To evaluate a new method for assessing the potential
      cost savings of COPD controller medications based on the incidence of
      exacerbations and their related resource utilization in the general population.
      METHODS: Patients with COPD (n = 1074) enrolled in a regional managed care system
      in the US were identified using administrative data and divided by their
      medication use into three groups (salbutamol, ipratropium and salmeterol).
      Exacerbations were captured using International Classification of Diseases, Ninth
      Edition (ICD-9) and current procedural terminology (CPT) codes, then logistic
      regression models were created that described the risk of exacerbations for each
      comparator group and exacerbation type over a 6-month period. A Monte Carlo
      simulation was then applied 1000 times to provide the range of potential
      exacerbation reductions and cost consequences in response to a range of
      hypothetical examples of COPD controller medications. RESULTS: Exacerbation
      events for each group could be modelled such that the events predicted by the
      Monte Carlo estimates were very close to the actual prevalences. The estimated
      cost per exacerbation avoided depended on the incidence of exacerbation in the
      various subpopulations, the assumed relative risk reduction, the projected daily
      cost for new therapy, and the costs of exacerbation treatment. CONCLUSIONS: COPD
      exacerbation events can be accurately modelled from the healthcare utilization
      data of a defined cohort with sufficient accuracy for cost-effectiveness
      analysis. Treatments that reduce the risk or severity of exacerbations are likely
      to be cost effective among those patients who have frequent exacerbations and
      hospitalizations.

PMID- 20799756
TI  - An economic evaluation of colesevelam when added to metformin-, insulin- or
      sulfonylurea-based therapies in patients with uncontrolled type 2 diabetes
      mellitus.
AB  - BACKGROUND: Several early studies demonstrated that bile acid sequestrants were
      useful for lowering lipid levels in patients with hypercholesterolaemia and may
      also be useful for lowering glucose levels in patients with type 2 diabetes
      mellitus (T2DM) uncontrolled on existing treatment (metformin-, insulin- or
      sulfonylurea-based therapies). OBJECTIVE: This study modelled efficacy and safety
      data from the three clinical trials to evaluate the cost effectiveness to US
      Managed Care Organizations of add-on treatment with colesevelam for reducing
      diabetes-related complications. METHODS: Three randomized controlled trials in
      patients with T2DM and one in hyperlipidaemia established that colesevelam
      lowered both glycaemic and lipid parameters in adult patients participating in
      the studies. The validated 'diabetic risk equation' (DRE) and the 'LIPID
      cardiovascular risk equation' (LCRE) were used to translate the observed clinical
      benefits (surrogate markers related to T2DM [glycosylated haemoglobin {HbA(1c)}
      and fasting plasma glucose] and cardiovascular disease [low-density lipoprotein
      cholesterol {LDL-C}]). Performing an appropriate economic evaluation required the
      use of both the DRE and the LCRE. These equations parameterize the clinical
      efficacy measures as continuous, facilitating their application to clinical trial
      results as well as the replication of other well established epidemiological
      data. Tobit regressions were applied to a large commercially available managed
      care administrative claims database (2000-6), Integrated Health Care Services
      (IHCS), to evaluate the incremental costs associated with each type of diabetic
      complication. Costs were inflated to 2010 values using the Healthcare Consumer
      Price Index, while second- and third-year cost savings were discounted at 5% to
      the current year. Bootstrap sampling with 5000 samples of 100 patients per cohort
      was conducted, varying the number of events avoided as well as their associated
      cost. RESULTS: With established metformin-, insulin- or sulfonylurea-based
      therapies, the addition of colesevelam significantly reduced HbA(1c) by
      approximately 0.5% (p < 0.001) in all three studies. In addition, colesevelam
      reduced placebo-adjusted LDL-C by 12.8-16.7% (p < 0.001). Using the DRE and LCRE
      equations, the total savings from reductions in diabetes-related and
      cardiovascular events were $US3543, $US4074 and $US3855 for colesevelam added to
      metformin-, insulin- and sulfonylurea-based regimens in patients with normal
      lipid levels. After subtracting the cost of colesevelam, first-year savings were
      $US1326, $US1852 and $US1629 in the metformin, insulin and sulfonylurea studies,
      respectively, for patients with raised lipid levels. CONCLUSIONS: In adult
      patients with T2DM, the addition of colesevelam to metformin-, insulin- or
      sulfonylurea-based therapies significantly improves glycaemic control while also
      reducing LDL-C, and these improvements could translate into substantial cost
      reductions due to reductions in the rates of diabetes-related and cardiovascular
      complications.

PMID- 20799757
TI  - Hepatic veno-occlusive disease: a chemotherapy-related toxicity in children with
      malignancies.
AB  - Hepatic veno-occlusive disease (VOD) is a major manifestation of liver toxicity
      associated with conventional and high-dose chemotherapy in children affected by
      hematologic malignancies and certain solid tumors. Clinically, patients present
      with jaundice, painful hepatomegaly, and fluid retention, which may evolve into
      multi-organ failure, a hallmark of severe disease. The pathogenesis is complex
      and not completely understood, but the damage to sinusoidal endothelium,
      typically caused by toxic metabolites released from antineoplastic drugs, is
      thought to play a crucial role, together with cytokine activation, immune
      deregulation, and coagulopathy. Diagnosis is based on clinical criteria supported
      by characteristic ultrasound findings, with the gold standard investigation being
      hepatic-venous pressure gradient measurement and biopsy. Several treatment
      options have been tested; the most convincing approach to date is the use of
      defibrotide, a novel oligonucleotide with antithrombotic and antiplatelet
      aggregating properties, as well as endothelial-stabilizing effects. This agent,
      together with other specific forms of supportive care, has shown efficacy in the
      treatment of established VOD and promising results in the prevention of VOD in
      pediatric patients receiving chemotherapy.

PMID- 20799758
TI  - Antivirals for influenza: strategies for use in pediatrics.
AB  - Influenza infection is annually responsible for significant morbidity and
      mortality, particularly among the very young and old. Recently updated guidelines
      recommend influenza vaccination of all children aged 6 months to 18 years;
      however, childhood vaccination remains underutilized. Furthermore, concerns over
      the reduced efficacy of vaccination in children have further heightened the need
      for effective treatment schemes. Antiviral therapies have emerged as attractive
      options in the battle against influenza infection. These agents include the
      adamantanes (amantadine and rimantadine) and neuraminidase inhibitors (zanamivir,
      oseltamivir, and peramivir). Broad-scale use of adamantane antivirals has been
      severely limited in recent years because of high resistance rates and their
      inability to cover influenza type B. Neuraminidase inhibitors cover influenza
      types A and B, and have been promulgated to first-line therapy because of
      historically low resistance rates and relatively infrequent side effects.
      Moreover, these agents are effective options in combating non-seasonal influenza
      strains, including H5N1 and pandemic 2009 H1N1. Oseltamivir may be particularly
      appealing for treating children since it is available in multiple oral dosage
      formulations, whereas commercially available zanamivir use is limited in young
      children because it requires inhalation. However, the emergence of resistance to
      oseltamivir among influenza A strains may limit its usefulness. Additional
      concerns with neuraminidase inhibitor use in pediatrics center around emerging
      reports, primarily from Japan, that have temporally linked oseltamivir to
      significant neuropsychiatric events in children of varying ages. Numerous novel
      antiviral agents are under development, but most are far from market approval. In
      addition to treating and preventing the initial burden of pediatric influenza
      infection, antiviral therapies may significantly reduce secondary bacterial
      infections (including pneumonia and otitis media), unnecessary antibiotic
      prescribing, and healthcare-associated costs.

PMID- 20799759
TI  - Pentoxifylline in preterm neonates: a systematic review.
AB  - Sepsis, necrotizing enterocolitis (NEC), and chronic lung disease (CLD) in
      preterm neonates are associated with significant mortality and morbidity,
      including long-term neurodevelopmental impairment and socioeconomic burden. Safe
      and effective drugs for the prevention and treatment of these conditions are
      urgently needed. Pentoxifylline, a synthetic theobromine derivative, is a non
      steroidal immunomodulating agent with unique hemorrheologic effects which has
      been used in a range of infectious, vascular, and inflammatory conditions in
      adults and children. The unique properties of pentoxifylline explain its
      potential benefits in preterm neonates with sepsis, NEC, and CLD, conditions
      characterized by activation of the inflammatory cytokine cascade, free radical
      toxicity, and impaired microcirculation. Pentoxifylline has anti-inflammatory
      properties resulting from inhibition of erythrocyte phosphodiesterase. It lowers
      blood viscosity and improves microcirculation and tissue perfusion. As a
      phosphodiesterase inhibitor, pentoxifylline downregulates pro-inflammatory
      cytokines such as tumor necrosis factor-alpha, interleukin-6, and interferon
      gamma. Methylxanthines, including caffeine, theophylline, and theobromine are
      relatively non-toxic drugs; of these, theobromine is the least toxic.
      Pentoxifylline-related significant adverse events are thus very rare. Unlike
      other methylxanthines, pentoxifylline does not have significant cardiac and
      bronchodilating effects at therapeutic doses. Although it is contraindicated in
      adults with recent cerebral hemorrhage due to its effect on platelets, red blood
      cells, and plasma fibrinogen levels, no significant adverse effects including
      thrombocytopenia and bleeding have been reported in critically ill preterm
      neonates with sepsis or NEC after treatment with pentoxifylline. Based on data
      from pilot randomized trials and observational studies, our systematic review
      suggests that pentoxifylline may reduce mortality and/or morbidity in preterm
      neonates with sepsis, NEC, and CLD. Results of experimental studies also indicate
      that pentoxifylline may potentially be beneficial in meconium aspiration syndrome
      and hypoxic ischemic encephalopathy. Given the substantial burden of sepsis, NEC,
      and CLD in high-risk preterm neonates, and the findings of this systematic
      review, pentoxifylline needs to be evaluated urgently as a preventative and
      therapeutic agent for these conditions in randomized controlled trials that can
      detect minimal clinically significant effect sizes. Further clinical and
      experimental studies are also necessary to evaluate whether pentoxifylline is
      safe and effective in meconium aspiration syndrome and hypoxic ischemic
      encephalopathy.

PMID- 20799760
TI  - Ketoprofen pharmacokinetics, efficacy, and tolerability in pediatric patients.
AB  - The NSAID ketoprofen is used widely in the management of inflammatory and
      musculoskeletal conditions, pain, and fever in children and adults.
      Pharmacokinetic studies show that drug exposure after a single intravenous dose
      is similar in children and adults (after dose normalization), and thus similar
      mg/kg bodyweight dosing may be used in children and adults. Ketoprofen crosses
      the blood-brain barrier and therefore has the potential to cause central
      analgesic effects. Ketoprofen has been investigated in children for the treatment
      of pain and fever, peri- and postoperative pain, and inflammatory pain
      conditions. The results of four clinical trials in febrile conditions with the
      oral syrup formulation indicate that ketoprofen is as effective as acetaminophen
      (paracetamol) and ibuprofen, allowing children to rapidly return to daily
      activities with improvements in sleep quality and appetite. Studies of ketoprofen
      in the management of postoperative pain indicate that ketoprofen is a highly
      effective analgesic when administered perioperatively for a variety of surgical
      types, by a variety of routes, and whether given preoperatively or
      postoperatively. For adenoidectomy, intravenous ketoprofen provided superior
      postoperative analgesic efficacy compared with placebo. Analgesic efficacy was
      similar with intravenous, intramuscular, or rectal routes of administration, but
      oral administration just before surgery was inferior to intravenous
      administration in this setting. In patients undergoing a tonsillectomy,
      intravenous ketoprofen was superior to intravenous tramadol in terms of the need
      for postoperative rescue analgesia, but did not remove the need for rescue opioid
      therapy in these patients. Intravenous ketoprofen had superior postoperative
      analgesic efficacy to placebo when given as an adjuvant to epidural sufentanil
      analgesia after major surgery. Oral ketoprofen has shown efficacy in the
      treatment of juvenile rheumatoid arthritis. Ketoprofen is generally well
      tolerated in pediatric patients. Most of the adverse events reported are mild and
      transient, and are similar to those observed with other NSAIDs. Long-term
      tolerability has not yet been fully established in children, but data from three
      studies in >900 children indicate that oral ketoprofen is well tolerated when
      administered for up to 3 weeks after surgery. In conclusion, ketoprofen is
      effective and well tolerated in children for the control of post-surgical pain
      and for the control of pain and fever in inflammatory conditions.

PMID- 20799761
TI  - Clinical significance of medication reconciliation in children admitted to a UK
      pediatric hospital: observational study of neurosurgical patients.
AB  - BACKGROUND: In December 2007, the National Institute for Health and Clinical
      Excellence and the National Patient Safety Agency in the UK (NICE-NPSA) published
      guidance that recommends all adults admitted to hospital receive medication
      reconciliation, usually by pharmacy staff. A costing and report tool was provided
      indicating a resource requirement of 12.9 million pounds for England per year.
      Pediatric patients are excluded from this guidance. OBJECTIVE: To determine the
      clinical significance of medication reconciliation in children on admission to
      hospital. METHODS: A prospective observational study included pediatric patients
      admitted to a neurosurgical ward at Birmingham Children's Hospital, Birmingham,
      England, between September 2006 and March 2007. Medication reconciliation was
      conducted by a pharmacist after the admission of each of 100 consecutive eligible
      patients aged 4 months to 16 years. The clinical significance of prescribing
      disparities between pre-admission medications and initial admission medication
      orders was determined by an expert multidisciplinary panel and quantified using
      an analog scale. The main outcome measure was the clinical significance of
      unintentional variations between hospital admission medication orders and
      physician-prescribed pre-admission medication for repeat (continuing)
      medications. RESULTS: Initial admission medication orders for children differed
      from prescribed pre-admission medication in 39% of cases. Half of all resulting
      prescribing variations in this setting had the potential to cause moderate or
      severe discomfort or clinical deterioration. These results mirror findings for
      adults. CONCLUSIONS: The introduction of medication reconciliation in children on
      admission to hospital has the potential to reduce discomfort or clinical
      deterioration by reducing unintentional changes to repeat prescribed medication.
      Consequently, there is no justification for the omission of children from the
      NICE-NPSA guidance concerning medication reconciliation in hospitals, and costing
      tools should include pediatric patients.

PMID- 20799762
TI  - The role of rapid antigen testing for influenza in the era of molecular
      diagnostics.
AB  - Rapid antigen testing for influenza has been both maligned and revered since its
      conception. Microbiologists have long lamented the lack of sensitivity of
      commercial rapid influenza detection tests (RIDTs), whereas many clinicians have
      eschewed their utility by emphasizing the value of definitely diagnosing
      influenza at the patient's bedside. RIDTs, although quick and easy to perform,
      are widely accepted as being less sensitive than traditional culture techniques
      and newer molecular methods, including reverse-transcription polymerase chain
      reaction (RT-PCR). Moreover, the performance characteristics of RIDTs vary
      widely, and their applications as clinical diagnostic tools are not well
      understood. In contrast, traditional techniques are time consuming and require
      significant expertise to perform. Often, the delay in diagnosing influenza
      through these methods has little impact on patient care. The benefits of
      achieving a diagnosis of influenza at the point of care are numerous and include
      increased access to appropriate antivirals, appropriate patient cohorting for
      infection control purposes, and better resource utilization. Therefore, it
      behooves the microbiology community to communicate these issues to clinicians and
      to work to improve the sensitivity of RIDTs.

PMID- 20799763
TI  - Human papillomavirus DNA testing for cervical cancer screening: practical aspects
      in developing countries.
AB  - Cervical cancer is the second most common cancer in women worldwide, and the most
      common cause of death from cancer in women in the developing world. Cervical
      cancer represents the only gynecologic cancer that can be prevented through
      regular screening. Although there are established screening programs in the
      Western world that have effectively reduced the burden of cervical cancer, these
      programs have relied on insensitive screening technologies that depend on the
      long preinvasive phase of cervical carcinogenesis. The developing world faces
      specific additional challenges in implementing a successful cervical cancer
      screening program. The association between cervical cancers and human
      papillomavirus (HPV) make testing for the presence of HPV DNA a valuable
      screening tool. This review focuses on practical aspects of the implementation
      and delivery of HPV testing as the primary cervical cancer screening strategy in
      the developing world, and attempts to offer some solutions to the real-world
      challenges faced in these regions.

PMID- 20799764
TI  - Comparative evaluation of nested PCR and conventional smear methods for the
      detection of Mycobacterium tuberculosis in sputum samples.
AB  - BACKGROUND: With 1.8 million new cases each year, India carries 20% of the global
      burden of tuberculosis, a situation that is now further exacerbated with the
      emergence of drug resistance. The current diagnostic technique suggested by the
      Government of India's Revised National Tuberculosis Control Programme is Ziehl
      Neelsen staining of a sputum smear. This technique is known to be inadequate.
      OBJECTIVE: The aim of this study was to evaluate nested PCR (nPCR) in the
      detection of pulmonary tuberculosis in sputum samples in comparison with
      conventional smear findings, in an effort to improve detection rates from those
      obtained by the smear-alone approach. STUDY DESIGN: Patients attending a tertiary
      care hospital (situated in a rural area of Vellore district) with clinical
      suspicion of pulmonary tuberculosis were prospectively recruited from mid-April
      2009 to mid-December 2009 and investigated. The sputum samples were stained by
      Ziehl-Neelsen staining for smear examination. DNA extracted from concentrated
      sputum was tested by nPCR, targeting the IS6110 sequence in the Mycobacterium
      tuberculosis genome. RESULTS: Among 84 patients tested (median age 45.5 years),
      80.95% were from the rural community and 19.05% were from the peri-urban
      community. Seventeen patients (20.24%; mid-p 95% CI 31.5, 52.4) tested positive
      by the smear examination and 35 (41.67%; mid-p 95% CI 12.7, 29.8) tested positive
      by nPCR. The difference in detection rates was statistically significant (chi(2)
      = 9.02; p = 0.002). The kappa coefficient between smear findings and nPCR
      findings was 0.47, which was a statistically significant agreement (Z = 4.91; p <
      0.0001). CONCLUSION: This report describes the molecular detection of M.
      tuberculosis in patients' sputum samples tested by the nPCR format, using IS6110
      as a target sequence. A high prevalence of pulmonary tuberculosis was identified
      by the nPCR assay, which was shown to have a significantly higher detection rate
      than conventional smear staining.

PMID- 20799765
TI  - Cost effectiveness of interferon-gamma release assay versus chest X-ray for
      tuberculosis screening of BCG-vaccinated elderly populations.
AB  - BACKGROUND: The prevalence of tuberculosis (TB) in the elderly is higher than
      that in the general population, and elderly populations are considered a high
      risk group. Currently, annual TB screening of Bacille Calmette-Guerin (BCG)
      vaccinated people aged over 65 years is performed by an annual chest x-ray
      examination (CXR) in Japan. Interferon-gamma release assays (QuantiFERON-TB Gold
      and QuantiFERON-TB Gold In-Tube [QFT]) are new alternatives to the tuberculin
      skin test to diagnose latent TB infection (LTBI) that have no cross-reactivity
      with the BCG vaccine. We evaluated the cost effectiveness of QFT versus CXR
      versus no screening in BCG-vaccinated elderly populations. METHODS: We
      constructed a Markov model to evaluate the cost effectiveness of QFT, CXR, and no
      screening. The target population was a hypothetical cohort of 1000
      immunocompetent 65-year-olds, using a societal perspective and a lifetime
      horizon. All costs and clinical benefits were discounted at a fixed annual rate
      of 3%. RESULTS: In the base-case analysis, a no-screening strategy resulted in
      the lowest cost ($US303.51; 14.6475 quality-adjusted life-years [QALYs]) compared
      with CXR ($US393.22; 14.6477 QALYs) and QFT ($US525.45; 14.6516 QALYs) [year 2008
      values]. The sensitivity of QFT, as well as the prevalence of TB and LTBI,
      influenced the cost effectiveness; when the sensitivity of QFT was higher than
      0.89, QFT became more cost effective than providing no screening. As the
      prevalence of LTBI and TB increased, the QFT strategy became progressively more
      cost effective. CONCLUSIONS: Providing no routine TB screening is currently the
      most cost-effective strategy for BCG-vaccinated elderly populations in Japan.
      There appears to be little role for CXR in TB screening of elderly populations.
      These findings may be applicable to other countries with intermediate and high TB
      risks when choosing optimal TB screening of elderly populations.

PMID- 20799766
TI  - Frequent reoccurrence of hypoglycemia in a type 2 diabetic patient with insulin
      antibodies.
AB  - BACKGROUND: Insulin antibody (IAb) may be produced in patients receiving long
      term, animal-derived insulin, leading to insulin resistance or hypoglycemia.
      There have been very few reports of hypoglycemia caused by IAb in patients taking
      recombinant human insulin. CASE REPORT: We report the case of an 82-year-old male
      patient with type 2 diabetes mellitus who suffered repeated episodes of severe
      hypoglycemia-related symptoms (including coma) prior to admission. The patient
      had been taking Novolin 30R, a premixed human insulin. The patient's IAb level
      was markedly elevated, and hypoglycemia caused by recombinant human insulin
      treatment-induced IAb production was diagnosed. Acarbose and metformin were
      prescribed, and the patient recovered uneventfully. The patient ceased taking
      these medications, and he was subsequently treated with recombinant human insulin
      to combat hyperglycemia. This was followed by reoccurrence of hypoglycemic coma.
      The patient was advised to avoid taking recombinant human insulin for the rest of
      his life and to control hyperglycemia with acarbose and metformin. CONCLUSIONS:
      Although rare, hypoglycemia caused by recombinant human insulin-induced IAb
      production should be considered in patients with type 2 diabetes who experience
      repeated episodes of hypoglycemia.

PMID- 20799768
TI  - Photoacoustic lifetime imaging of dissolved oxygen using methylene blue.
AB  - Measuring distribution of dissolved oxygen in biological tissue is of prime
      interest for cancer diagnosis, prognosis, and therapy optimization. Tumor hypoxia
      indicates poor prognosis and resistance to radiotherapy. Despite its major
      clinical significance, no current imaging modality provides direct imaging of
      tissue oxygen. We present preliminary results demonstrating the potential of
      photoacoustic lifetime imaging (PALI) for noninvasive, 3-D imaging of tissue
      oxygen. The technique is based on photoacoustic probing of the excited state
      lifetime of methylene blue (MB) dye. MB is an FDA-approved water soluble dye with
      a peak absorption at 660 nm. A double pulse laser system (pump probe) is used to
      excite the dye and probe its transient absorption by detecting photoacoustic
      emission. The relaxation rate of MB depends linearly on oxygen concentration. Our
      measurements show high photoacoustic signal contrast at a probe wavelength of 810
      nm, where the excited state absorption is more than four times higher than the
      ground state absorption. Imaging of a simple phantom is demonstrated. We conclude
      by discussing possible implementations of the technique in clinical settings and
      combining it with photodynamic therapy (PDT) for real-time therapy monitoring.

PMID- 20799767
TI  - Primary bilateral Burkitt lymphoma of the lactating breast: a case report and
      review of the literature.
AB  - Burkitt lymphoma (BL) is a highly aggressive neoplasm, which frequently affects
      the ileocecal region in the sporadic form and the jaw in the endemic form;
      however, the breast is a rare primary site of this tumor. Here we describe a case
      of primary bilateral breast BL presenting during lactation in a 23-year-old
      woman. Excisional biopsy of breast masses demonstrated a B-cell lymphoma with a
      characteristic 'starry sky' pattern highly suggestive of BL. The neoplastic cells
      strongly expressed CD20 and CD10, and showed proliferative activity as measured
      by Ki-67. An IGH-MYC gene fusion indicating the presence of a typical Burkitt
      translocation t(8;14)(q24;q32) in the tumor tissue was detected by fluorescent in
      situ hybridization. The present case, along with a comprehensive review of the
      literature, demonstrates that BL of the breast should be considered in the
      differential diagnosis of lesions of the breast during lactation. Whether
      hormonal or antigenic factors trigger Burkitt lymphomagenesis in the lactating
      breast warrants further investigation.

PMID- 20799769
TI  - Needle-compatible single fiber bundle image guide reflectance endoscope.
AB  - We developed a miniaturized high-resolution low-cost reflectance-mode fiber
      microscope (RFM) aimed at optical tissue biopsy applications using a polarized
      imaging configuration to suppress background noise from specular reflectance. The
      RFM is equipped with an air-cooled light-emitting-diode illumination module and a
      single 450-microm outer-diameter fiber bundle image guide compatible with a 20
      gauge needle. The dual illumination and image acquisition nature of the fiber
      bundle simplifies the system and reduces the total cost. Imaging tests with a
      United States Air Force resolution target demonstrate a lateral resolution of
      approximately 3.5 microm. The performance of the imaging system is evaluated by
      examining samples of cells and excised human tissue. Still and video rate images
      are obtainable in reflectance mode using intrinsic contrast.

PMID- 20799770
TI  - Quantitative fluorescence tomography using a trimodality system: in vivo
      validation.
AB  - A fully integrated trimodality fluorescence, diffuse optical, and x-ray computed
      tomography (FT/DOT/XCT) system for small animal imaging is reported in this work.
      The main purpose of this system is to obtain quantitatively accurate fluorescence
      concentration images using a multimodality approach. XCT offers anatomical
      information, while DOT provides the necessary background optical property map to
      improve FT image accuracy. The quantitative accuracy of this trimodality system
      is demonstrated in vivo. In particular, we show that a 2-mm-diam fluorescence
      inclusion located 8 mm deep in a nude mouse can only be localized when functional
      a priori information from DOT is available. However, the error in the recovered
      fluorophore concentration is nearly 87%. On the other hand, the fluorophore
      concentration can be accurately recovered within 2% error when both DOT
      functional and XCT structural a priori information are utilized together to guide
      and constrain the FT reconstruction algorithm.

PMID- 20799771
TI  - Optical scatter changes at the onset of apoptosis are spatially associated with
      mitochondria.
AB  - We combine optical scatter imaging (OSI) with fluorescence imaging of
      mitochondria to investigate the spatial relationship between the optical scatter
      signal and the location and structure of mitochondria within endothelial cells
      undergoing apoptosis. The OSI data corroborate our previous results showing a
      decrease in the intensity ratio of wide-to-narrow angle scatter [optical scatter
      image ratio (OSIR)] during the first 60 min of apoptosis. In addition, we find
      here that this is followed by an increase in OSIR concurrent with mitochondrial
      fragmentation. We demonstrate that the dynamic change in light scattering is
      spatially associated with subcellular regions containing fluorescently labeled
      mitochondria, and remains absent from adjacent nonfluorescent regions dominated
      by other organelles. These results lend strong support to the hypothesis that
      mitochondria act as the source of the optical scatter changes measured at the
      onset of apoptosis.

PMID- 20799772
TI  - Study of back-scattering microspectrum for stomach cells at single-cell scale.
AB  - A fiber confocal backscattering (FCBS) spectrometer is developed based on fiber
      confocal microscopy and light scattering theory. The FCBS spectrometer can
      provide imaging and spectral information simultaneously at the cellular scale.
      Normal stomach epithelial cell line GES-1 and cancerous cell line NCI-N87 are
      measured and their spectral results show that backscattering intensity from NCI
      N87 cells is stronger than that from GES-1 cells in 500 to 800 nm, and the GES-1
      cells scattering spectra show regular intensity changes, while the NCI-N87 cells
      do not. The experiments prove that the FCBS spectrometer is able to distinguish
      cancerous cells from normal stomach cells at the cellular level. The spectrometer
      could be further developed into a noninvasive optical technology for early cancer
      detection.

PMID- 20799773
TI  - Combined optical coherence tomography and electroretinography system for in vivo
      simultaneous morphological and functional imaging of the rodent retina.
AB  - A combined ultrahigh resolution optical coherence tomography (UHROCT) and a
      electroretinography (ERG) system is presented for simultaneous imaging of the
      retinal structure and physiological response to light stimulation in the rodent
      eye. The 1060-nm UHROCT system provides approximately 3x5 microm (axialxlateral)
      resolution in the rat retina and time resolution of 22 micros. A custom-designed
      light stimulator integrated into the UHROCT imaging probe provides light stimuli
      with user-selected color, duration, and intensity. The performance of the
      combined system is demonstrated in vivo in healthy rats, and in a rat model of
      drug-induced outer retinal degeneration. Experimental results show correlation
      between the observed structural and physiological changes in the healthy and
      degenerated retina.

PMID- 20799774
TI  - Integrated autofluorescence endoscopic imaging and point-wise spectroscopy for
      real-time in vivo tissue measurements.
AB  - We report on the development of an integrated point-wise spectroscopy and
      autofluorescence (AF) endoscopic imaging technique for real-time in vivo tissue
      measurements at endoscopy. We implement a unique point spectrum optical design to
      realize real-time AF imaging and AF or diffuse reflectance (DR) spectroscopy
      measurements from a small area of tissue of interest on the AF image. We
      demonstrate that both the AF image and the point-wise AF/DR spectra can be
      simultaneously acquired from the oral cavity in vivo within 0.1 s, suggesting the
      potential of the integrated spectroscopy and endoscopic imaging technique
      developed to facilitate in vivo tissue diagnosis and characterization at
      endoscopy.

PMID- 20799775
TI  - In vivo volumetric imaging of the human upper eyelid with ultrahigh-resolution
      optical coherence tomography.
AB  - The upper eyelid is a biological tissue with complex structure, essential for the
      maintenance of an optically clear ocular surface due to its physical (blinking)
      effect. The Meibomian glands (MGs) are structures that lie beneath the surface of
      the inner eyelid and are partially responsible for the production of the
      superficial oily layer of the tear film. The MGs are only superficially visible
      under magnification when the eyelid is everted. We present for the first time in
      vivo 3-D images of healthy and inflamed human MGs. Tomograms were acquired from
      the tarsal plate of everted human eyelids with a 1060-nm ultrahigh-resolution
      optical coherence tomography (UHOCT) system, with approximately 3 microm x 10
      microm (axial x lateral) resolution in biological tissue at the rate of 91,911 A
      scans/s. Comparison with histology shows that the UHOCT images reveal a spatial
      distribution of structures that appear to correspond with the MGs' acini and
      ducts (in healthy subjects), and accumulation of heterogeneous, highly scattering
      biological material and clear fluids in the visibly blocked glands. Noninvasive,
      volumetric high-resolution morphological imaging of the human tarsal area could
      have a significant impact in the clinical diagnosis of inflammatory and
      noninflammatory lid pathologies.

PMID- 20799776
TI  - Population-based visual acuity in the presence of defocus well predicted by
      classical theory.
AB  - According to classical theory, visual acuity (VA) can be modeled using the
      intersection of the eye's modulation transfer function with a retinal threshold
      function. To date, there have been limited attempts to validate this methodology
      by comparing theory with actual measured data. We use the methodology to predict
      the visual acuity in the presence of defocus of a population of cataract patients
      implanted with diffractive multifocal intraocular lenses. For the prediction, we
      used a set of physiological eye models that include chromatic and higher order
      aberrations. We found that the simulations correlated strongly to the clinical
      outcomes (R(2)=0.93). While the simulated VA of the eye models was systematically
      0.05 logMAR units lower (better acuity) than the clinical results, this
      difference was independent of defocus (p=0.98). These results show that when the
      simple and straightforward classical theory is applied using physiological eye
      models, accurate predictions of the VA, and through-focus VA of a population can
      be made. This method may be suited for predicting visual performance of new
      cataract and refractive treatments.

PMID- 20799777
TI  - Growth of melanoma brain tumors monitored by photoacoustic microscopy.
AB  - Melanoma is a primary malignancy that is known to metastasize to the brain and
      often causes death. The ability to image the growth of brain melanoma in vivo can
      provide new insights into its evolution and response to therapies. In our study,
      we use a reflection mode photoacoustic microscopy (PAM) system to detect the
      growth of melanoma brain tumor in a small animal model. The melanoma tumor cells
      are implanted in the brain of a mouse at the beginning of the test. Then, PAM is
      used to scan the region of implantation in the mouse brain, and the growth of the
      melanoma is monitored until the death of the animal. It is demonstrated that PAM
      is capable of detecting and monitoring the brain melanoma growth noninvasively in
      vivo.

PMID- 20799778
TI  - Phasor representation of oxy- and deoxyhemoglobin concentrations: what is the
      meaning of out-of-phase oscillations as measured by near-infrared spectroscopy?
AB  - We propose a phasor representation for oscillations at a given frequency (or
      relatively narrow frequency band) of hemoglobin concentrations in tissue, as well
      as hemoglobin concentrations measured by near-infrared spectroscopy. This
      representation provides a straightforward visualization of the phase
      relationships between oscillations of oxy-, deoxy-, and total hemoglobin
      concentrations ([HbO], [Hb], and [HbT], respectively). We observe that measured
      oscillations of [Hb] and [HbO] with a phase difference that is neither 0 nor pi
      must result from the combination of different physiological processes that are
      out of phase (or time shifted) with respect to each other. Finally, we propose
      the use of cross-correlation phasors to map phase relationships and correlation
      levels among hemoglobin oscillations measured at spatially distinct locations at
      a given frequency. Such a representation may find a natural application in the
      study of functional connectivity networks in the brain.

PMID- 20799779
TI  - Selected topics in biophotonics: photodynamic therapy and optical
      micromanipulation for biophotonics.

PMID- 20799780
TI  - Photodynamic therapy: superficial and interstitial illumination.
AB  - Photodynamic therapy (PDT) is reviewed using the treatment of skin tumors as an
      example of superficial lesions and prostate cancer as an example of deep-lying
      lesions requiring interstitial intervention. These two applications are among the
      most commonly studied in oncological PDT, and illustrate well the different
      challenges facing the two modalities of PDT-superficial and interstitial. They
      thus serve as good examples to illustrate the entire field of PDT in oncology.
      PDT is discussed based on the Lund University group's over 20 yr of experience in
      the field. In particular, the interplay between optical diagnostics and dosimetry
      and the delivery of the therapeutic light dose are highlighted. An interactive
      multiple-fiber interstitial procedure to deliver the required therapeutic dose
      based on the assessment of light fluence rate and sensitizer concentration and
      oxygen level throughout the tumor is presented.

PMID- 20799781
TI  - Light forces the pace: optical manipulation for biophotonics.
AB  - The biomedical sciences have benefited immensely from photonics technologies in
      the last 50 years. This includes the application of minute forces that enable the
      trapping and manipulation of cells and single molecules. In terms of the area of
      biophotonics, optical manipulation has made a seminal contribution to our
      understanding of the dynamics of single molecules and the microrheology of cells.
      Here we present a review of optical manipulation, emphasizing its impact on the
      areas of single-molecule studies and single-cell biology, and indicating some of
      the key experiments in the fields.

PMID- 20799782
TI  - Shape anisotropy induces rotations in optically trapped red blood cells.
AB  - A combined experimental and theoretical study is carried out to probe the
      rotational behavior of red blood cells (RBCs) in a single beam optical trap. We
      induce shape changes in RBCs by altering the properties of the suspension medium
      in which live cells float. We find that certain shape anisotropies result in the
      rotation of optically trapped cells. Indeed, even normal (healthy) RBCs can be
      made to rotate using linearly polarized trapping light by altering the osmotic
      stress the cells are subjected to. Hyperosmotic stress is found to induce shape
      anisotropies. We also probe the effect of the medium's viscosity on cell
      rotation. The observed rotations are modeled using a Langevin-type equation of
      motion that takes into account frictional forces that are generated as RBCs
      rotate in the medium. We observe good correlation between our measured data and
      calculated results.

PMID- 20799783
TI  - Effect of long- and short-term exposure to laser light at 1070 nm on growth of
      Saccharomyces cerevisiae.
AB  - The effect of a 1070-nm continuous and pulsed wave ytterbium fiber laser on the
      growth of Saccharomyces cerevisiae single cells is investigated over a time span
      of 4 to 5 h. The cells are subjected to optical traps consisting of two
      counterpropagating plane wave beams with a uniform flux along the x, y axis. Even
      at the lowest continuous power investigated-i.e., 0.7 mW-the growth of S.
      cerevisiae cell clusters is markedly inhibited. The minimum power required to
      successfully trap single S. cerevisiae cells in three dimensions is estimated to
      be 3.5 mW. No threshold power for the photodamage, but instead a continuous
      response to the increased accumulated dose is found in the regime investigated
      from 0.7 to 2.6 mW. Furthermore, by keeping the delivered dose constant and
      varying the exposure time and power-i.e. pulsing-we find that the growth of S.
      cerevisiae cells is increasingly inhibited with increasing power. These results
      indicate that growth of S. cerevisiae is dependent on both the power as well as
      the accumulated dose at 1070 nm.

PMID- 20799784
TI  - Transient transfection of mammalian cells using a violet diode laser.
AB  - We demonstrate the first use of the violet diode laser for transient mammalian
      cell transfection. In contrast to previous studies, which showed the generation
      of stable cell lines over a few weeks, we develop a methodology to transiently
      transfect cells with an efficiency of up to approximately 40%. Chinese hamster
      ovary (CHO-K1) and human embryonic kidney (HEK293) cells are exposed to a tightly
      focused 405-nm laser in the presence of plasmid DNA encoding for a mitochondrial
      targeted red fluorescent protein. We report transfection efficiencies as a
      function of laser power and exposure time for our system. We also show, for the
      first time, that a continuous wave laser source can be successfully applied to
      selective gene silencing experiments using small interfering RNA. This work is a
      major step towards an inexpensive and portable phototransfection system.

PMID- 20799785
TI  - Phototransfection of mammalian cells using femtosecond laser pulses: optimization
      and applicability to stem cell differentiation.
AB  - Recently, femtosecond laser pulses have been utilized for the targeted
      introduction of genetic matter into mammalian cells. This rapidly expanding and
      developing novel optical technique using a tightly focused laser light beam is
      called phototransfection. Extending previous studies [Stevenson et al., Opt.
      Express 14, 7125-7133 (2006)], we show that femtosecond lasers can be used to
      phototransfect a range of different cell lines, and specifically that this novel
      technology can also transfect mouse embryonic stem cell colonies with
      approximately 25% efficiency. Notably, we show the ability of differentiating
      these cells into the extraembryonic endoderm using phototransfection.
      Furthermore, we present two new findings aimed at optimizing the
      phototransfection method and improving applicability: first, the influence of the
      cell passage number on the transfection efficiency is explored and, second, the
      ability to enhance the transfection efficiency via whole culture treatments. Our
      results should encourage wider uptake of this methodology.

PMID- 20799786
TI  - In vivo carotid artery closure by laser activation of hyaluronan-embedded gold
      nanorods.
AB  - We prove the first application of near-infrared-absorbing gold nanorods (GNRs)
      for in vivo laser closure of a rabbit carotid artery. GNRs are first
      functionalized with a biopolymeric shell and then embedded in hyaluronan, which
      gives a stabilized and handy laser-activable formulation. Four rabbits undergo
      closure of a 3-mm longitudinal incision performed on the carotid artery by means
      of a 810-nm diode laser in conjunction with the topical application of the GNRs
      composite. An effective surgery is obtained by using a 40-W/cm(2) laser power
      density. The histological and electron microscopy evaluation after a 30-day
      follow-up demonstrates complete healing of the treated arteries with full re
      endothelization at the site of GNRs application. The absence of microgranuloma
      formation and/or dystrophic calcification is evidence that no host reaction to
      nanoparticles interspersed through the vascular tissue occurred. The observation
      of a reshaping and associated blue shift of the NIR absorption band of GNRs after
      laser treatment supports the occurrence of a self-terminating process, and thus
      of additional safety of the minimally invasive laser procedure. This study
      underlines the feasibility of using GNRs for in vivo laser soldering
      applications, which represents a step forward toward the introduction of
      nanotechnology-based therapies in minimally invasive clinical practices.

PMID- 20799787
TI  - Contrast-enhanced digital holographic imaging of cellular structures by
      manipulating the intracellular refractive index.
AB  - The understanding of biological reactions and evaluation of the significance for
      living cells strongly depends on the ability to visualize and quantify these
      processes. Digital holographic microscopy (DHM) enables quantitative phase
      contrast imaging for high resolution and minimal invasive live cell analysis
      without the need of labeling or complex sample preparation. However, due to the
      rather homogeneous intracellular refractive index, the phase contrast of
      subcellular structures is limited and often low. We analyze the impact of the
      specific manipulation of the intracellular refractive index by microinjection on
      the DHM phase contrast. Glycerol is chosen as osmolyte, which combines high
      solubility in aqueous solutions and biological compatibility. We show that the
      intracellular injection of glycerol causes a contrast enhancement that can be
      explained by a decrease of the cytosolic refractive index due to a water influx.
      The underlying principle is proven by experiments inducing cell shrinkage and
      with fixated cells. The integrity of the cell membrane is considered as a
      prerequisite and allows a reversible cell swelling and shrinking within a certain
      limit. The presented approach to control the intracellular phase contrast
      demonstrated for the example of DHM opens prospects for applications with other
      quantitative phase contrast imaging methods.

PMID- 20799789
TI  - Signal power decrease due to fringe washout as an extension of the limited
      Doppler flow measurement range in spectral domain optical coherence tomography.
AB  - The recently introduced new phase-dependent Doppler model for spectral domain
      optical coherence tomography (SD OCT) has shown that the simple linear relation
      between the Doppler phase shift and the axial velocity component of an obliquely
      moving sample is not valid. Additionally, for nearly transverse sample motion
      with high velocities the phase shift will approach a constant value.
      Consequently, for small Doppler angles the velocity measurement range of the
      phase-resolved Doppler analysis is limited in SD OCT. Since these undesirable
      small Doppler angles can not be prevented, for example, in the in vivo 3-D
      measurement, we introduce a novel method extending the limited velocity detection
      range taking the signal power decrease due to fringe washout in SD OCT into
      account. The signal damping of an obliquely moving sample is presented as a
      function of the axial and transverse displacement by a universally valid contour
      plot and does not correspond simply to the sum of the axial and transverse
      effect. A quantitative combination of the Doppler analysis and the signal-damping
      method is presented with a flow phantom model. The practicability of this new
      combined method is presented for the blood flow of the saphenous artery in the in
      vivo mouse model.

PMID- 20799788
TI  - Toward guidance of epicardial cardiac radiofrequency ablation therapy using
      optical coherence tomography.
AB  - Radiofrequency ablation (RFA) is the standard of care to cure many cardiac
      arrhythmias. Epicardial ablation for the treatment of ventricular tachycardia has
      limited success rates due in part to the presence of epicardial fat, which
      prevents proper rf energy delivery, inadequate contact of ablation catheter with
      tissue, and increased likelihood of complications with energy delivery in close
      proximity to coronary vessels. A method to directly visualize the epicardial
      surface during RFA could potentially provide feedback to reduce complications and
      titrate rf energy dose by detecting critical structures, assessing probe contact,
      and confirming energy delivery by visualizing lesion formation. Currently, there
      is no technology available for direct visualization of the heart surface during
      epicardial RFA therapy. We demonstrate that optical coherence tomography (OCT)
      imaging has the potential to fill this unmet need. Spectral domain OCT at 1310 nm
      is employed to image the epicardial surface of freshly excised swine hearts using
      a microscope integrated bench-top scanner and a forward imaging catheter probe.
      OCT image features are observed that clearly distinguish untreated myocardium,
      ablation lesions, epicardial fat, and coronary vessels, and assess tissue contact
      with catheter-based imaging. These results support the potential for real-time
      guidance of epicardial RFA therapy using OCT imaging.

PMID- 20799791
TI  - In vivo functional retinal optical coherence tomography.
AB  - An experimental design for noninvasive assessment of neural retinal tissue
      function with enhanced sensitivity is presented. By matching the response
      detection to a defined flicker frequency stimulus similar to heterodyne
      detection, the response signal will be shifted out of the low-frequency noise and
      the specificity of response detection will be strongly enhanced. Optimal
      measurement parameters are discussed, such as the function and timing of the
      response function to a single flash stimulus. The results indicate responses on
      the order of 200 ms that have been probed with our frequency-encoded approach
      using 5 Hz flickering. Preliminary results indicate the feasibility of our
      measurement concept to assess small changes in reflectivity with enhanced
      sensitivity. A functional tomogram for response localization and quantification
      is introduced.

PMID- 20799790
TI  - Quantitative tool for rapid disease mapping using optical coherence tomography
      images of azoxymethane-treated mouse colon.
AB  - Optical coherence tomography (OCT) can provide new insight into disease
      progression and therapy by enabling nondestructive, serial imaging of in vivo
      cancer models. In previous studies, we have shown the utility of endoscopic OCT
      for identifying adenomas in the azoxymethane-treated mouse model of colorectal
      cancer and tracking disease progression over time. Because of improved imaging
      speed made possible through Fourier domain imaging, three-dimensional imaging of
      the entire mouse colon is possible. Increased amounts of data can facilitate more
      accurate classification of tissue but require more time on the part of the
      researcher to sift through and identify relevant data. We present quantitative
      software for automatically identifying potentially diseased areas that can be
      used to create a two-dimensional "disease map" from a three-dimensional Fourier
      domain OCT data set. In addition to sensing inherent changes in tissue that occur
      during disease development, the algorithm is sensitive to exogeneous highly
      scattering gold nanoshells that can be targeted to disease biomarkers. The
      results of the algorithm were compared to histological diagnosis. The algorithm
      was then used to assess the ability of gold nanoshells targeted to epidermal
      growth factor receptor in vivo to enable functional OCT imaging.

PMID- 20799792
TI  - In vivo measurement of epidermal thickness changes associated with tumor
      promotion in murine models.
AB  - The characterization of tissue morphology in murine models of pathogenesis has
      traditionally been carried out by excision of affected tissues with subsequent
      immunohistological examination. Excision-based histology provides a limited two
      dimensional presentation of tissue morphology at the cost of halting disease
      progression at a single time point and sacrifice of the animal. We investigate
      the use of noninvasive reflectance mode confocal scanning laser microscopy
      (rCSLM) as an alternative tool to biopsy in documenting epidermal hyperplasia in
      murine models exposed to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate
      (TPA). An automated technique utilizing average axial rCSLM reflectance profiles
      is used to extract epidermal thickness values from rCSLM data cubes. In
      comparisons to epidermal thicknesses determined from hematoxylin and eosin (H&E)
      stained tissue sections, we find no significant correlation to rCSLM-derived
      thickness values. This results from method-specific artifacts: physical
      alterations of tissue during H&E preparation in standard histology and specimen
      induced abberations in rCSLM imaging. Despite their disagreement, both histology
      and rCSLM methods reliably measure statistically significant thickness changes in
      response to TPA exposure. Our results demonstrate that in vivo rCSLM imaging
      provides epithelial biologists an accurate noninvasive means to monitor cutaneous
      pathogenesis.

PMID- 20799794
TI  - Structural analysis of the antimalarial drug halofantrine by means of Raman
      spectroscopy and density functional theory calculations.
AB  - The structure of the antimalarial drug halofantrine is analyzed by means of
      density functional theory (DFT) calculations, IR, and Raman spectroscopy. Strong,
      selective enhancements of the Raman bands of halofantrine at 1621 and 1590 cm(-1)
      are discovered by means of UV resonance Raman spectroscopy with excitation
      wavelength lambda(exc)=244 nm. These signal enhancements can be exploited for a
      localization of small concentrations of halofantrine in a biological environment.
      The Raman spectrum of halofantrine is calculated by means of DFT calculations
      [B3LYP/6-311+G(d,p)]. The calculation is very useful for a thorough mode
      assignment of the Raman bands of halofantrine. The strong bands at 1621 and 1590
      cm(-1) in the UV Raman spectrum are assigned to combined C[Double Bond]C
      stretching vibrations in the phenanthrene ring of halofantrine. These bands are
      considered as putative marker bands for pipi interactions with the biological
      target molecules. The calculation of the electron density demonstrates a strong
      distribution across the phenanthrene ring of halofantrine, besides the electron
      withdrawing effect of the Cl and CF(3) substituents. This strong and even
      electron density distribution supports the hypothesis of pipi stacking as a
      possible mode of action of halofantrine. Complementary IR spectroscopy is
      performed for an investigation of vibrations of polar functional groups of the
      halofantrine molecule.

PMID- 20799793
TI  - Optical tomography method that accounts for tilted chest wall in breast imaging.
AB  - The chest wall underneath breast tissue distorts light reflection measurements,
      especially measurements obtained from distant source-detector pairs. For patients
      with a chest wall located at a shallower depth, the chest-wall effect needs to be
      considered in the image reconstruction procedure. Following our previous studies,
      this work systemically evaluates the performance of a two-layer model-based
      reconstruction using the finite element method, and compares it with the
      performance of the semi-infinite model. The results obtained from simulations and
      phantom experiments show that the two-layer model improves the light
      quantification of the targets. The improvements are attributed to improved
      background estimation and more accurate weight matrix calculation using a two
      layer model compared to the semi-infinite model. Fitted two-layer background
      optical properties obtained from a group of ten patients with chest walls located
      less than 2 cm deep are more representative of breast tissue and chest-wall
      optical properties.

PMID- 20799795
TI  - Fluorescence excitation on monolithically integrated all-polymer chips.
AB  - All-polymer chips with integrated optical waveguides and microfluidic channels
      were built as a platform for fluorescence excitation of biological samples. Their
      functionality has been shown for four cases: (i) fluorescence of labeled
      phospholipids inside a microfluidic channel, (ii) fluorescence of stained cells
      inside a microfluidic channel, (iii) fluorescence of labeled phospholipids on top
      of a polymer waveguide, and (iv) fluorescence of stained cells on top of a
      polymer waveguide.

PMID- 20799796
TI  - Modeling light propagation through bacterial colonies and its correlation with
      forward scattering patterns.
AB  - Bacterial colonies play an important role in the isolation and identification of
      bacterial species, and plating on a petri dish is still regarded as the gold
      standard for confirming the cause of an outbreak situation. A bacterial colony
      consists of millions of densely packed individual bacteria along with matrices
      such as extracellular materials. When a laser is directed through a colony,
      complicated structures encode their characteristic signatures, which results in
      unique forward scattering patterns. We investigate the connection between the
      morphological parameters of a bacterial colony and corresponding forward
      scattering patterns to understand bacterial growth morphology. A colony elevation
      is modeled with a Gaussian profile, which is defined with two critical
      parameters: center thickness and diameter. Then, applying the scalar diffraction
      theory, we compute an amplitude modulation via light attenuation from multiple
      layers of bacteria while a phase modulation is computed from the colony profile.
      Computational results indicate that center thickness plays a critical role in the
      total number of diffraction rings while the magnitude of the slope of a colony
      determines the maximum diffraction angle. Experimental validation is performed by
      capturing the scattering patterns, monitoring colony diameters via phase contrast
      microscope, and acquiring the colony profiles via confocal displacement meter.

PMID- 20799797
TI  - Alterations in the characteristic size distributions of subcellular scatterers at
      the onset of apoptosis: effect of Bcl-xL and Bax/Bak.
AB  - Optical scatter imaging is used to estimate organelle size distributions in
      immortalized baby mouse kidney cells treated with 0.4 microM staurosporine to
      induce apoptosis. The study comprises apoptosis competent iBMK cells (W2)
      expressing the proapoptotic proteins Bax/Bak, apoptosis resistant Bax/Bak null
      cells (D3), and W2 and D3 cells expressing yellow fluorescent protein (YFP) or
      YFP fused to the antiapoptotic protein Bcl-x(L) (YFP-Bcl-x(L)). YFP expression is
      diffuse within the transfected cells, while YFP-Bcl-x(L) is localized to the
      mitochondria. Our results show a significant increase in the mean subcellular
      particle size from approximately 1.1 to 1.4 microm in both Bax/Bak expressing and
      Bax/Bak null cells after 60 min of STS treatment compared to DMSO-treated control
      cells. This dynamic is blocked by overexpression of YFP-Bcl-x(L) in Bax/Bak
      expressing cells, but is less significantly inhibited by YFP-Bcl-x(L) in Bax/Bak
      null cells. Our data suggest that the increase in subcellular particle size at
      the onset of apoptosis is modulated by Bcl-x(L) in the presence of Bax/Bak, but
      it occurs upstream of the final commitment to programmed cell death.
      Mitochondrial localization of YFP-Bcl-x(L) and the finding that micron-sized
      particles give rise to the scattering signal further suggest that alterations in
      mitochondrial morphology may underlie the observed changes in light scattering.

PMID- 20799798
TI  - Real-time observation of the effect of iron on receptor-mediated endocytosis of
      transferrin conjugated with quantum dots.
AB  - The optical properties of antiphotobleaching and the advantage of long-term
      fluorescence observation of quantum dots are fully adopted to study the effects
      of iron on the endocytosis of transferrin. Quantum dots are labeled for
      transferrin and endocytosis of transferrin in HeLa cells is observed under the
      normal state, iron overloading, and an iron-deficient state. In these three
      states, the fluorescence undergoes a gradual process of first dark, then light,
      and finally dark, indicating the endocytosis of transferrin. The fluorescence
      intensity analysis shows that a platform emerges when fluorescence changes to a
      certain degree in the three states. Experienced a same period of time after
      platform, the fluorescence strength of cells in the normal state is 1.2 times the
      first value, and the iron-deficiency state is 1.4 times, but the iron overloading
      state was 0.85 times. We also find that the average fluorescence intensity in
      cells detected by the spectrophotometer in the iron-deficiency state is almost 7
      times than that in a high iron state. All this proves that iron overloading would
      slow the process, but iron deficiency would accelerate endocytosis. We advance a
      direct observational method that may contribute to further study of the
      relationship of iron and transferrin.

PMID- 20799799
TI  - Computational study of scattering from healthy and diseased red blood cells.
AB  - We present a comparative study of scattering from healthy red blood cells (RBCs)
      and diseased RBCs with deformed shapes. Scattering problems involving three
      dimensional RBCs are formulated accurately with the electric and magnetic current
      combined-field integral equation and solved efficiently by the multilevel fast
      multipole algorithm. We compare scattering cross section values obtained for
      different RBC shapes and different orientations. In this way, we determine strict
      guidelines to distinguish deformed RBCs from healthy RBCs and to diagnose various
      diseases using scattering cross section values. The results may be useful for
      designing new and improved flow cytometry procedures.

PMID- 20799800
TI  - Silver nanoparticle-induced degranulation observed with quantitative phase
      microscopy.
AB  - Monitoring a degranulation process in a live mast cell is a quite important issue
      in immunology and pharmacology. Because the size of a granule is normally much
      smaller than the resolution limit of an optical microscope system, there is no
      direct real-time live cell imaging technique for observing degranulation
      processes except for fluorescence imaging techniques. In this research, we
      propose optical quantitative phase microscopy (QPM) as a new observation tool to
      study degranulation processes in a live mast cell without any fluorescence
      labeling. We measure the cell volumes and the cross sectional profiles (x-z
      plane) of an RBL-2H3 cell and a HeLa cell, before and after they are exposed to
      calcium ionophore A23187 and silver nanoparticles (AgNPs). We verify that the
      volume and the cross sectional line profile of the RBL-2H3 cell were changed
      significantly when it was exposed to A23187. When 50 microg/mL of AgNP is used
      instead of A23187, the measurements of cell volume and cross sectional profiles
      indicate that RBL-2H3 cells also follow degranulation processes. Degranulation
      processes for these cells are verified by monitoring the increase of
      intracellular calcium ([Ca(2+)](i)) and histamine with fluorescent methods.

PMID- 20799802
TI  - Relationships of skin depths and temperatures when varying pulse repetition
      frequencies from 2.0-microm laser light incident on pig skin.
AB  - Human perception of 2.0-microm infrared laser irradiation has become significant
      in such disparate fields as law enforcement, neuroscience, and pain research.
      Several recent studies have found damage thresholds for single-pulse and
      continuous wave irradiations at this wavelength. However, the only publication
      using multiple-pulse irradiations was investigating the cornea rather than skin.
      Literature has claimed that the 2.0-microm light characteristic thermal diffusion
      time was as long as 300-ms. Irradiating the skin with 2.0-microm lasers to
      produce sensation should follow published recommendations to use pulses on the
      order of 10 to 100 ms, which approach the theoretical thermal diffusion time.
      Therefore, investigation of the heating of skin for a variety of laser pulse
      combinations was undertaken. Temperatures of ex vivo pig skin were measured at
      the surface and at three depths from pulse sequences of six different duty
      factors. Differences were found in temperature rise per unit exposure that did
      not follow a linear relation to duty factor. The differences can be explained by
      significant heat conduction during the pulses. Therefore, the common heat
      modeling assumption of thermal confinement during a pulse may need to be
      experimentally verified if the pulse approaches the theoretical thermal
      confinement time.

PMID- 20799801
TI  - Simulation of single-molecule trapping in a nanochannel.
AB  - The detection and trapping of single fluorescent molecules in solution within a
      nanochannel is studied using numerical simulations. As optical forces are
      insufficient for trapping molecules much smaller than the optical wavelength, a
      means for sensing a molecule's position along the nanochannel and adjusting
      electrokinetic motion to compensate diffusion is assessed. Fluorescence
      excitation is provided by two adjacently focused laser beams containing
      temporally interleaved laser pulses. Photon detection is time-gated, and the
      displacement of the molecule from the middle of the two foci alters the count
      rates collected in the two detection channels. An algorithm for feedback control
      of the electrokinetic motion in response to the timing of photons, to reposition
      the molecule back toward the middle for trapping and to rapidly reload the trap
      after a molecule photobleaches or escapes, is evaluated. While accommodating the
      limited electrokinetic speed and the finite latency of feedback imposed by
      experimental hardware, the algorithm is shown to be effective for trapping fast
      diffusing single-chromophore molecules within a micron-sized confocal region.
      Studies show that there is an optimum laser power for which loss of molecules
      from the trap due to either photobleaching or shot-noise fluctuations is
      minimized.

PMID- 20799803
TI  - In-vivo dynamic characterization of microneedle skin penetration using optical
      coherence tomography.
AB  - The use of microneedles as a method of circumventing the barrier properties of
      the stratum corneum is receiving much attention. Although skin disruption
      technologies and subsequent transdermal diffusion rates are being extensively
      studied, no accurate data on depth and closure kinetics of microneedle-induced
      skin pores are available, primarily due to the cumbersome techniques currently
      required for skin analysis. We report on the first use of optical coherence
      tomography technology to image microneedle penetration in real time and in vivo.
      We show that optical coherence tomography (OCT) can be used to painlessly measure
      stratum corneum and epidermis thickness, as well as microneedle penetration depth
      after microneedle insertion. Since OCT is a real-time, in-vivo, nondestructive
      technique, we also analyze skin healing characteristics and present quantitative
      data on micropore closure rate. Two locations (the volar forearm and dorsal
      aspect of the fingertip) have been assessed as suitable candidates for
      microneedle administration. The results illustrate the applicability of OCT
      analysis as a tool for microneedle-related skin characterization.

PMID- 20799804
TI  - Noninvasive imaging of prefrontal activation during attention-demanding tasks
      performed while walking using a wearable optical topography system.
AB  - Optical topography (OT) based on near-infrared spectroscopy is a noninvasive
      technique for mapping the relative concentration changes in oxygenated and
      deoxygenated hemoglobin (oxy- and deoxy-Hb, respectively) in the human cerebral
      cortex. In our previous study, we developed a small and light wearable optical
      topography (WOT) system that covers the entire forehead for monitoring prefrontal
      activation. In the present study, we examine whether the WOT system is applicable
      to OT measurement while walking, which has been difficult with conventional OT
      systems. We conduct OT measurements while subjects perform an attention-demanding
      (AD) task of balancing a ping-pong ball on a small card while walking. The
      measured time course and power spectra of the relative concentration changes in
      oxy- and deoxy-Hb show that the step-related changes in the oxy- and deoxy-Hb
      signals are negligible compared to the task-related changes. Statistical
      assessment of the task-related changes in the oxy-Hb signals show that the
      dorsolateral prefrontal cortex and rostral prefrontal area are significantly
      activated during the AD task. These results suggest that our functional imaging
      technique with the WOT system is applicable to OT measurement while walking, and
      will be a powerful tool for evaluating brain activation in a natural environment.

PMID- 20799805
TI  - Effect of ultrasound transducer face reflectivity on the light fluence inside a
      turbid medium in photoacoustic imaging.
AB  - Many endoscopic, intravascular, and transvaginal applications require light to be
      delivered through optical fibers in a reflection mode. For photoacoustic imaging
      in reflection geometry, the front-face reflectivity of the ultrasound transducer
      face imposes a boundary condition that affects the light fluence and its
      distribution inside a turbid medium. Understanding and characterizing this
      boundary condition is critical for maximizing tissue illumination and therefore
      the signal-to-noise ratio of the photoacoustic signal. We systematically analyze
      the light fluence under three typical commercial transducer faces having
      reflection coefficients of 1.4, 18, and 28%, and compare the results to a
      transducer face with 60% coefficient at the laser wavelength of 750 nm. Monte
      Carlo simulations and experimental results show that light fluence and
      distribution obtained inside a turbid medium with the use of the 60% reflection
      coefficient transducer face has a significant improvement over the others,
      especially at shallower depths.

PMID- 20799806
TI  - Highly reproducible swept-source, dispersion-encoded full-range biometry and
      imaging of the mouse eye.
AB  - We report a high-speed, dispersion-encoded, full-range (DEFR) swept-source
      optical coherence tomography system for in vivo ocular imaging and biometry of
      small animals. The fast DEFR algorithm removes the depth ambiguity, gives access
      to objects located at the zero delay position, and doubles the sampling depth to
      2x5.0 mm (at -101 to -71 dB sensitivity) in a single scan using 2048
      samples/depth scan 0.43 nm line width of a light source operating at 1056 nm with
      70 nm tuning range. The acquisition speed (frames of 512 depth scans in 18.3 ms)
      permits precise on-line monitoring during positioning and provides cross
      sectional views of the mouse eye. Preliminary studies demonstrate high
      throughput, reproducible assessment of multiple biometric features (e.g., day-to
      day reproducibility of axial length measurement +/-5.3 microm) that is
      insensitive to eye motion sufficient for long-term monitoring.

PMID- 20799807
TI  - Comprehensive investigation of three-dimensional diffuse optical tomography with
      depth compensation algorithm.
AB  - A depth compensation algorithm (DCA) can effectively improve the depth
      localization of diffuse optical tomography (DOT) by compensating the
      exponentially decreased sensitivity in the deep tissue. In this study, DCA is
      investigated based on computer simulations, tissue phantom experiments, and human
      brain imaging. The simulations show that DCA can largely improve the spatial
      resolution of DOT in addition to the depth localization, and DCA is also
      effective for multispectral DOT with a wide range of optical properties in the
      background tissue. The laboratory phantom experiment demonstrates that DCA can
      effectively differentiate two embedded objects at different depths in the medium.
      DCA is further validated by human brain imaging using a finger-tapping task. To
      our knowledge, this is the first demonstration to show that DCA is capable of
      accurately localizing cortical activations in the human brain in three
      dimensions.

PMID- 20799808
TI  - Combined multiphoton imaging and automated functional enucleation of porcine
      oocytes using femtosecond laser pulses.
AB  - Since the birth of "Dolly" as the first mammal cloned from a differentiated cell,
      somatic cell cloning has been successful in several mammalian species, albeit at
      low success rates. The highly invasive mechanical enucleation step of a cloning
      protocol requires sophisticated, expensive equipment and considerable
      micromanipulation skill. We present a novel noninvasive method for combined
      oocyte imaging and automated functional enucleation using femtosecond (fs) laser
      pulses. After three-dimensional imaging of Hoechst-labeled porcine oocytes by
      multiphoton microscopy, our self-developed software automatically identified the
      metaphase plate. Subsequent irradiation of the metaphase chromosomes with the
      very same laser at higher pulse energies in the low-density-plasma regime was
      used for metaphase plate ablation (functional enucleation). We show that fs laser
      based functional enucleation of porcine oocytes completely inhibited the
      parthenogenetic development without affecting the oocyte morphology. In contrast,
      nonirradiated oocytes were able to develop parthenogenetically to the blastocyst
      stage without significant differences to controls. Our results indicate that fs
      laser systems have great potential for oocyte imaging and functional enucleation
      and may improve the efficiency of somatic cell cloning.

PMID- 20799809
TI  - Principal component model of multispectral data for near real-time skin
      chromophore mapping.
AB  - Multispectral images of skin contain information on the spatial distribution of
      biological chromophores, such as blood and melanin. From this, parameters such as
      blood volume and blood oxygenation can be retrieved using reconstruction
      algorithms. Most such approaches use some form of pixelwise or volumetric
      reconstruction code. We explore the use of principal component analysis (PCA) of
      multispectral images to access blood volume and blood oxygenation in near real
      time. We present data from healthy volunteers under arterial occlusion of the
      forearm, experiencing ischemia and reactive hyperemia. Using a two-layered
      analytical skin model, we show reconstruction results of blood volume and
      oxygenation and compare it to the results obtained from our new spectral analysis
      based on PCA. We demonstrate that PCA applied to multispectral images gives near
      equivalent results for skin chromophore mapping and quantification with the
      advantage of being three orders of magnitude faster than the reconstruction
      algorithm.

PMID- 20799810
TI  - Analysis of the metabolic deterioration of ex vivo skin from ischemic necrosis
      through the imaging of intracellular NAD(P)H by multiphoton tomography and
      fluorescence lifetime imaging microscopy.
AB  - Ex vivo human skin has been used extensively for cosmeceutical and drug delivery
      studies, transplantable skin allografts, or skin flaps. However, it has a half
      life of a few days due to ischemic necrosis. Traditional methods of assessing
      viability can be time-consuming and provide limited metabolic information. Using
      multiphoton tomography and fluorescence lifetime imaging (MPT-FLIM) we assess
      ischemic necrosis of ex vivo skin by NAD(P)H autofluorescence intensity and
      fluorescence lifetime. Ex vivo skin is stored in the presence and absence of
      nutrient media (Dulbecco Modified Eagle Medium) at -20, 4, and 37 degrees C and
      room temperature over a 7-day time course to establish different rates of
      metabolic deterioration. At higher temperatures we observe a decrease in NAD(P)H
      autofluorescence, higher image noise, and a significant increase in the average
      fluorescence lifetime (tau(m)) from approximately 1000 to 2000 ps. Additionally,
      significant distortions in NAD(P)H fluorescence lifetime histograms correspond to
      the reduction in autofluorescence. Skin kept at 4 degrees C, with or without
      media, showed the least change. Our findings suggest that MPT-FLIM enables useful
      noninvasive optical biopsies to monitor the metabolic state and deterioration of
      human skin for research and clinical purposes.

PMID- 20799811
TI  - High-resolution retinal imaging through open-loop adaptive optics.
AB  - Using the liquid crystal spatial light modulator (LC-SLM) as the wavefront
      corrector, an open-loop adaptive optics (AO) system for fundus imaging in vivo is
      constructed. Compared with the LC-SLM closed-loop AO system, the light energy
      efficiency is increased by a factor of 2, which is helpful for the safety of
      fundus illumination in vivo. In our experiment, the subjective accommodation
      method is used to precorrect the defocus aberration, and three subjects with
      different myopia 0, -3, and -5 D are tested. Although the residual wavefront
      error after correction cannot to detected, the fundus images adequately
      demonstrate that the imaging system reaches the resolution of a single
      photoreceptor cell through the open-loop correction. Without dilating and
      cyclopleging the eye, the continuous imaging for 8 s is recorded for one of the
      subjects.

PMID- 20799812
TI  - Handheld array-based photoacoustic probe for guiding needle biopsy of sentinel
      lymph nodes.
AB  - By modifying a clinical ultrasound array system, we develop a novel handheld
      photoacoustic probe for image-guided needle biopsy. The integration of optical
      fiber bundles for pulsed laser light delivery enables photoacoustic image-guided
      insertion of a needle into rat axillary lymph nodes with accumulated indocyanine
      green (ICG). Strong photoacoustic contrast of the needle is achieved. After
      subcutaneous injection of the dye in the left forepaw, sentinel lymph nodes are
      easily detected, in vivo and in real time, beneath 2-cm-thick chicken breast
      overlaying the axillary region. ICG uptake in axillary lymph nodes is confirmed
      with fluorescence imaging both in vivo and ex vivo. These results demonstrate the
      clinical potential of this handheld photoacoustic system for facile
      identification and needle biopsy of sentinel lymph nodes for cancer staging and
      metastasis detection in humans.

PMID- 20799813
TI  - Lifetime-based tomographic multiplexing.
AB  - Near-infrared (NIR) fluorescence tomography of multiple fluorophores has
      previously been limited by the bandwidth of the NIR spectral regime and the broad
      emission spectra of most NIR fluorophores. We describe in vivo tomography of
      three spectrally overlapping fluorophores using fluorescence lifetime-based
      separation. Time-domain images are acquired using a voltage-gated, intensified
      charge-coupled device (CCD) in free-space transmission geometry with 750 nm
      Ti:sapphire laser excitation. Lifetime components are fit from the asymptotic
      portion of fluorescence decay curve and reconstructed separately with a lifetime
      adjusted forward model. We use this system to test the in vivo lifetime
      multiplexing suitability of commercially available fluorophores, and demonstrate
      lifetime multiplexing in solution mixtures and in nude mice. All of the
      fluorophores tested exhibit nearly monoexponential decays, with narrow in vivo
      lifetime distributions suitable for lifetime multiplexing. Quantitative
      separation of two fluorophores with lifetimes of 1.1 and 1.37 ns is demonstrated
      for relative concentrations of 1:5. Finally, we demonstrate tomographic imaging
      of two and three fluorophores in nude mice with fluorophores that localize to
      distinct organ systems. This technique should be widely applicable to imaging
      multiple NIR fluorophores in 3-D.

PMID- 20799814
TI  - Virtual biopsy of rat tympanic membrane using higher harmonic generation
      microscopy.
AB  - Multiharmonic optical microscopy has been widely applied in biomedical research
      due to its unique capability to perform noninvasive studies of biomaterials. In
      this study, virtual biopsy based on back-propagating multiple optical harmonics,
      combining second and third harmonics, is applied in unfixed rat tympanic
      membrane. We show that third harmonic generation can provide morphologic
      information on the epithelial layers of rat tympanic membrane as well as radial
      collagen fibers in middle fibrous layers, and that second harmonic generation can
      provide information on both radial and circular collagen fibers in middle fibrous
      layers. Through third harmonic generation, the capillary and red blood cells in
      the middle fibrous layer are also noted. Additionally, the 3-D relationship to
      adjacent bony structures and spatial variations in thickness and curvature are
      obtained. Our study demonstrates the feasibility of using a noninvasive optical
      imaging system for comprehensive evaluation of the tympanic membrane.

PMID- 20799815
TI  - Direct curvature correction for noncontact imaging modalities applied to
      multispectral imaging.
AB  - Noncontact optical imaging of curved objects can result in strong artifacts due
      to the object's shape, leading to curvature biased intensity distributions. This
      artifact can mask variations due to the object's optical properties, and makes
      reconstruction of optical/physiological properties difficult. In this work we
      demonstrate a curvature correction method that removes this artifact and recovers
      the underlying data, without the necessity of measuring the object's shape. This
      method is applicable to many optical imaging modalities that suffer from shape
      based intensity biases. By separating the spatially varying data (e.g.,
      physiological changes) from the background signal (dc component), we show that
      the curvature can be extracted by either averaging or fitting the rows and
      columns of the images. Numerical simulations show that our method is equivalent
      to directly removing the curvature, when the object's shape is known, and
      accurately recovers the underlying data. Experiments on phantoms validate the
      numerical results and show that for a given image with 16.5% error due to
      curvature, the method reduces that error to 1.2%. Finally, diffuse multispectral
      images are acquired on forearms in vivo. We demonstrate the enhancement in image
      quality on intensity images, and consequently on reconstruction results of blood
      volume and oxygenation distributions.

PMID- 20799816
TI  - Combined image-processing algorithms for improved optical coherence tomography of
      prostate nerves.
AB  - Cavernous nerves course along the surface of the prostate gland and are
      responsible for erectile function. These nerves are at risk of injury during
      surgical removal of a cancerous prostate gland. In this work, a combination of
      segmentation, denoising, and edge detection algorithms are applied to time-domain
      optical coherence tomography (OCT) images of rat prostate to improve
      identification of cavernous nerves. First, OCT images of the prostate are
      segmented to differentiate the cavernous nerves from the prostate gland. Then, a
      locally adaptive denoising algorithm using a dual-tree complex wavelet transform
      is applied to reduce speckle noise. Finally, edge detection is used to provide
      deeper imaging of the prostate gland. Combined application of these three
      algorithms results in improved signal-to-noise ratio, imaging depth, and
      automatic identification of the cavernous nerves, which may be of direct benefit
      for use in laparoscopic and robotic nerve-sparing prostate cancer surgery.

PMID- 20799817
TI  - Improving image segmentation performance and quantitative analysis via a computer
      aided grading methodology for optical coherence tomography retinal image
      analysis.
AB  - We demonstrate quantitative analysis and error correction of optical coherence
      tomography (OCT) retinal images by using a custom-built, computer-aided grading
      methodology. A total of 60 Stratus OCT (Carl Zeiss Meditec, Dublin, California) B
      scans collected from ten normal healthy eyes are analyzed by two independent
      graders. The average retinal thickness per macular region is compared with the
      automated Stratus OCT results. Intergrader and intragrader reproducibility is
      calculated by Bland-Altman plots of the mean difference between both gradings and
      by Pearson correlation coefficients. In addition, the correlation between Stratus
      OCT and our methodology-derived thickness is also presented. The mean thickness
      difference between Stratus OCT and our methodology is 6.53 microm and 26.71
      microm when using the inner segment/outer segment (IS/OS) junction and outer
      segment/retinal pigment epithelium (OS/RPE) junction as the outer retinal border,
      respectively. Overall, the median of the thickness differences as a percentage of
      the mean thickness is less than 1% and 2% for the intragrader and intergrader
      reproducibility test, respectively. The measurement accuracy range of the OCT
      retinal image analysis (OCTRIMA) algorithm is between 0.27 and 1.47 microm and
      0.6 and 1.76 microm for the intragrader and intergrader reproducibility tests,
      respectively. Pearson correlation coefficients demonstrate R(2)>0.98 for all
      Early Treatment Diabetic Retinopathy Study (ETDRS) regions. Our methodology
      facilitates a more robust and localized quantification of the retinal structure
      in normal healthy controls and patients with clinically significant intraretinal
      features.

PMID- 20799818
TI  - Combined photoacoustic and oblique-incidence diffuse reflectance system for
      quantitative photoacoustic imaging in turbid media.
AB  - While photoacoustic imaging is capable of producing high-resolution biomedical
      images with optical absorption contrast, optical property quantification has thus
      far remained challenging. One reason for this is that laser-induced photoacoustic
      signal amplitudes are proportional to not only the local optical absorption
      coefficient, but also the local laser fluence in the tissue. Unfortunately, local
      laser fluence is often unknown, but could possibly be estimated if local bulk
      tissue optical properties were known. One method to estimate tissue optical
      properties is a technique known as oblique incidence diffuse reflectance (OIR).
      We report on an integrated OIR and photoacoustic imaging system and demonstrate,
      using phantom experiments, improved ability to quantitatively estimate optical
      properties of a turbid medium.

PMID- 20799819
TI  - Fluorescence imaging of membrane dynamics in living cells.
AB  - Methods of wide-field fluorescence microscopy for measuring membrane dynamics of
      living cells are described, including spectral imaging as well as anisotropy
      imaging of the membrane marker 6-dodecanoyl-2-dimethylamino naphthalene
      (laurdan). Plasma membranes are selected by illumination with an evanescent
      electromagnetic field and distinguished from intracellular membranes assessed by
      whole-cell illumination. While fluorescence spectra of laurdan appeared red
      shifted with decreasing membrane stiffness, fluorescence anisotropy and
      rotational correlation times were reduced with increasing membrane fluidity.
      Membrane stiffness was found to increase with decreasing temperature and
      increasing amounts of cholesterol and was always higher for the plasma membrane
      than for intracellular membranes. These effects may have some clinical relevance
      in the research of drug resistance or cell aging.

PMID- 20799820
TI  - Three-dimensional optical method for integrated visualization of mouse islet
      microstructure and vascular network with subcellular-level resolution.
AB  - Microscopic visualization of islets of Langerhans under normal and diabetic
      conditions is essential for understanding the pathophysiology of the disease. The
      intrinsic opacity of pancreata, however, limits optical accessibility for high
      resolution light microscopy of islets in situ. Because the standard microtome
      based, 2-D tissue analysis confines visualization of the islet architecture at a
      specific cut plane, 3-D representation of image data is preferable for islet
      assessment. We applied optical clearing to minimize the random light scattering
      in the mouse pancreatic tissue. The optical-cleared pancreas allowed penetrative,
      3-D microscopic imaging of the islet microstructure and vasculature.
      Specifically, the islet vasculature was revealed by vessel painting-lipophilic
      dye labeling of blood vessels-for confocal microscopy. The voxel-based confocal
      micrographs were digitally processed with projection algorithms for 3-D
      visualization. Unlike the microtome-based tissue imaging, this optical method for
      penetrative imaging of mouse islets yielded clear, continuous optical sections
      for an integrated visualization of the islet microstructure and vasculature with
      subcellular-level resolution. We thus provide a useful imaging approach to change
      our conventional planar view of the islet structure into a 3-D panorama for
      better understanding of the islet physiology.

PMID- 20799821
TI  - Comparison of optical coherence tomography, microcomputed tomography, and
      histology at a three-dimensionally imaged trabecular bone sample.
AB  - We investigate optical coherence tomography (OCT) as a method for imaging bone.
      The OCT images are compared directly to those of the standard methods of bone
      histology and microcomputed tomography (microCT) on a single, fixed human femoral
      trabecular bone sample. An advantage of OCT over bone histology is its
      noninvasive nature. OCT also images the lamellar structure of trabeculae at
      slightly higher contrast than normal bone histology. While microCT visualizes the
      trabecular framework of the whole sample, OCT can image additionally cells with a
      penetration depth limited approximately to 1 mm. The most significant advantage
      of OCT, however, is the absence of toxic effects (no ionizing radiation), i.e.,
      continuous images may be made and individual cell tracking may be performed. The
      penetration depth of OCT, however, limits its use to small animal models and
      small bone organ cultures.

PMID- 20799822
TI  - Third-harmonic generation for the study of Caenorhabditis elegans embryogenesis.
AB  - Live microscopy techniques (i.e., differential interference contrast, confocal
      microscopy, etc.) have enabled the understanding of the mechanisms involved in
      cells and tissue formation. In long-term studies, special care must be taken in
      order to avoid sample damage, restricting the applicability of the different
      microscopy techniques. We demonstrate the potential of using third-harmonic
      generation (THG) microscopy for morphogenesis/embryogenesis studies in living
      Caenorhabditis elegans (C. elegans). Moreover, we show that the THG signal is
      obtained in all the embryo development stages, showing different tissue/structure
      information. For this research, we employ a 1550-nm femtosecond fiber laser and
      demonstrate that the expected water absorption at this wavelength does not
      severely compromise sample viability. Additionally, this has the important
      advantage that the THG signal is emitted at visible wavelengths (516 nm).
      Therefore, standard collection optics and detectors operating near maximum
      efficiency enable an optimal signal reconstruction. All this, to the best of our
      knowledge, demonstrates for the first time the noninvasiveness and strong
      potential of this particular wavelength to be used for high-resolution four
      dimensional imaging of embryogenesis using unstained C. elegans in vivo samples.

PMID- 20799823
TI  - Acquiring 3-D information about thick objects from differential interference
      contrast images using texture extraction.
AB  - The extraction of 3-D morphological information about thick objects is explored
      in this work. We extract this information from 3-D differential interference
      contrast (DIC) images by applying a texture detection method. Texture extraction
      methods have been successfully used in different applications to study biological
      samples. A 3-D texture image is obtained by applying a local entropy-based
      texture extraction method. The use of this method to detect regions of blastocyst
      mouse embryos that are used in assisted reproduction techniques such as in vitro
      fertilization is presented as an example. Results demonstrate the potential of
      using texture detection methods to improve morphological analysis of thick
      samples, which is relevant to many biomedical and biological studies.
      Fluorescence and optical quadrature microscope phase images are used for
      validation.

PMID- 20799824
TI  - Shack-Hartmann wavefront-sensor-based adaptive optics system for multiphoton
      microscopy.
AB  - The imaging depth of two-photon excitation fluorescence microscopy is partly
      limited by the inhomogeneity of the refractive index in biological specimens.
      This inhomogeneity results in a distortion of the wavefront of the excitation
      light. This wavefront distortion results in image resolution degradation and
      lower signal level. Using an adaptive optics system consisting of a Shack
      Hartmann wavefront sensor and a deformable mirror, wavefront distortion can be
      measured and corrected. With adaptive optics compensation, we demonstrate that
      the resolution and signal level can be better preserved at greater imaging depth
      in a variety of ex-vivo tissue specimens including mouse tongue muscle, heart
      muscle, and brain. However, for these highly scattering tissues, we find signal
      degradation due to scattering to be a more dominant factor than aberration.

PMID- 20799825
TI  - Intravascular optical coherence tomography on a beating heart model.
AB  - The advantages and limitations of using a beating heart model in the development
      of intravascular optical coherence tomography are discussed. The model fills the
      gap between bench experiments, performed on phantoms and excised arteries, and
      whole animal in-vivo preparations. The beating heart model is stable for many
      hours, allowing for extended measurement times and multiple imaging sessions
      under in-vivo conditions without the complications of maintaining whole-animal
      preparation. The perfusate supplying the heart with nutrients can be switched
      between light scattering blood to a nonscattering perfusate to allow the optical
      system to be optimized without the need of an efficient blood displacement
      strategy. Direct access to the coronary vessels means that there is no need for x
      ray fluoroscopic guidance of the catheter to the heart, as is the case in whole
      animal preparation. The model proves to be a valuable asset in the development of
      our intravascular optical coherence tomography technology.

PMID- 20799826
TI  - Optical spectral imaging of degeneration of articular cartilage.
AB  - Osteoarthritis (OA) is a common musculoskeletal disorder often diagnosed during
      arthroscopy. In OA, visual color changes of the articular cartilage surface are
      typically observed. We demonstrate in vitro the potential of visible light
      spectral imaging (420 to 720 nm) to quantificate these color changes. Intact
      bovine articular cartilage samples (n=26) are degraded both enzymatically using
      the collagenase and mechanically using the emery paper (P60 grit, 269 microm
      particle size). Spectral images are analyzed by using standard CIELAB color
      coordinates and the principal component analysis (PCA). After collagenase
      digestion, changes in the CIELAB coordinates and projection of the spectra to PCA
      eigenvector are statistically significant (p<0.05). After mechanical degradation,
      the grinding tracks could not be visualized in the RGB presentation, i.e., in the
      visual appearance of the sample to the naked eye under the D65 illumination.
      However, after projecting to the chosen eigenvector, the grinding tracks are
      revealed. The tracks are also seen by using only one wavelength, i.e., 469 nm,
      however, the contrast in the projection image is 1.6 to 2.5 times higher. Our
      results support the idea that the spectral imaging can be used for evaluation of
      the integrity of the cartilage surface.

PMID- 20799827
TI  - Dark-field light scattering imaging of living cancer cell component from birth
      through division using bioconjugated gold nanoprobes.
AB  - Novel methods and technologies that could extend and complement the capabilities
      of the prevailing fluorescence microscope in following the cell cycle under
      different perturbations are highly desirable in the area of biological and
      biomedical imaging. We report a newly designed instrument for long-term light
      scattering live cell imaging based on integrating a homebuilt environmental cell
      incubation minichamber and an angled dark-field illumination system into a
      conventional inverted light microscope. Peptide-conjugated gold nanoparticles
      that are selectively delivered to either the cytoplasmic or nuclear region of the
      cell are used as light scattering contrast agents. The new system enables us to
      carry out continuous and intermittence-free dark-field live cell imaging over
      several tens of hours. A variety of applications of this imaging system are
      demonstrated, such as monitoring the nuclear uptake of peptide-conjugated gold
      nanoparticles, tracking the full cycle of cancer cells from birth to division,
      following the chromosome dynamics during cell mitosis, and observing the
      intracellular distribution of gold nanoparticles after cell division. We also
      discuss the overall effect of nuclear targeting gold nanoparticles on the cell
      viability of parent and daughter cells.

PMID- 20799828
TI  - Automated identification of abnormal metaphase chromosome cells for the detection
      of chronic myeloid leukemia using microscopic images.
AB  - Karyotyping is an important process to classify chromosomes into standard classes
      and the results are routinely used by the clinicians to diagnose cancers and
      genetic diseases. However, visual karyotyping using microscopic images is time
      consuming and tedious, which reduces the diagnostic efficiency and accuracy.
      Although many efforts have been made to develop computerized schemes for
      automated karyotyping, no schemes can get be performed without substantial human
      intervention. Instead of developing a method to classify all chromosome classes,
      we develop an automatic scheme to detect abnormal metaphase cells by identifying
      a specific class of chromosomes (class 22) and prescreen for suspicious chronic
      myeloid leukemia (CML). The scheme includes three steps: (1) iteratively segment
      randomly distributed individual chromosomes, (2) process segmented chromosomes
      and compute image features to identify the candidates, and (3) apply an adaptive
      matching template to identify chromosomes of class 22. An image data set of 451
      metaphase cells extracted from bone marrow specimens of 30 positive and 30
      negative cases for CML is selected to test the scheme's performance. The overall
      case-based classification accuracy is 93.3% (100% sensitivity and 86.7%
      specificity). The results demonstrate the feasibility of applying an automated
      scheme to detect or prescreen the suspicious cancer cases.

PMID- 20799829
TI  - Superresolved digital in-line holographic microscopy for high-resolution lensless
      biological imaging.
AB  - Digital in-line holographic microscopy (DIHM) is a modern approach capable of
      achieving micron-range lateral and depth resolutions in three-dimensional
      imaging. DIHM in combination with numerical imaging reconstruction uses an
      extremely simplified setup while retaining the advantages provided by holography
      with enhanced capabilities derived from algorithmic digital processing. We
      introduce superresolved DIHM incoming from time and angular multiplexing of the
      sample spatial frequency information and yielding in the generation of a
      synthetic aperture (SA). The SA expands the cutoff frequency of the imaging
      system, allowing submicron resolutions in both transversal and axial directions.
      The proposed approach can be applied when imaging essentially transparent (low
      concentration dilutions) and static (slow dynamics) samples. Validation of the
      method for both a synthetic object (U.S. Air Force resolution test) to quantify
      the resolution improvement and a biological specimen (sperm cells biosample) are
      reported showing the generation of high synthetic numerical aperture values
      working without lenses.

PMID- 20799830
TI  - Single-cell analysis of dihydroartemisinin-induced apoptosis through reactive
      oxygen species-mediated caspase-8 activation and mitochondrial pathway in ASTC-a
      1 cells using fluorescence imaging techniques.
AB  - Dihydroartemisinin (DHA), a front-line antimalarial herbal compound, has been
      shown to possess promising anticancer activity with low toxicity. We have
      previously reported that DHA induced caspase-3-dependent apoptosis in human lung
      adenocarcinoma cells. However, the cellular target and molecular mechanism of DHA
      induced apoptosis is still poorly defined. We use confocal fluorescence
      microscopy imaging, fluorescence resonance energy transfer, and fluorescence
      recovery after photobleaching techniques to explore the roles of DHA-elicited
      reactive oxygen species (ROS) in the DHA-induced Bcl-2 family proteins
      activation, mitochondrial dysfunction, caspase cascade, and cell death. Cell
      Counting Kit-8 assay and flow cytometry analysis showed that DHA induced ROS
      mediated apoptosis. Confocal imaging analysis in a single living cell and Western
      blot assay showed that DHA triggered ROS-dependent Bax translocation,
      mitochondrial membrane depolarization, alteration of mitochondrial morphology,
      cytochrome c release, caspase-9, caspase-8, and caspase-3 activation, indicating
      the coexistence of ROS-mediated mitochondrial and death receptor pathway.
      Collectively, our findings demonstrate for the first time that DHA induces cell
      apoptosis by triggering ROS-mediated caspase-8/Bid activation and the
      mitochondrial pathway, which provides some novel insights into the application of
      DHA as a potential anticancer drug and a new therapeutic strategy by targeting
      ROS signaling in lung adenocarcinoma therapy in the future.

PMID- 20799831
TI  - Parametric imaging of cancer with optical coherence tomography.
AB  - We present a parametric optical coherence tomography (OCT) technique to improve
      contrast between malignant and healthy non-neoplastic tissue. The technique
      incorporates a fully automated method to extract tissue attenuation
      characteristics. Results are represented visually as a parametric en face image,
      where the parameter used for contrast is indicative of the relative optical
      attenuation coefficient of the tissue. We present the first parametric OCT images
      of human lymph nodes containing malignant cells, and demonstrate improved tissue
      contrast over en face OCT images.

PMID- 20799832
TI  - Scanning elastic scattering spectroscopy detects metastatic breast cancer in
      sentinel lymph nodes.
AB  - A novel method for rapidly detecting metastatic breast cancer within excised
      sentinel lymph node(s) of the axilla is presented. Elastic scattering
      spectroscopy (ESS) is a point-contact technique that collects broadband optical
      spectra sensitive to absorption and scattering within the tissue. A statistical
      discrimination algorithm was generated from a training set of nearly 3000
      clinical spectra and used to test clinical spectra collected from an independent
      set of nodes. Freshly excised nodes were bivalved and mounted under a fiber-optic
      plate. Stepper motors raster-scanned a fiber-optic probe over the plate to
      interrogate the node's cut surface, creating a 20x20 grid of spectra. These
      spectra were analyzed to create a map of cancer risk across the node surface.
      Rules were developed to convert these maps to a prediction for the presence of
      cancer in the node. Using these analyses, a leave-one-out cross-validation to
      optimize discrimination parameters on 128 scanned nodes gave a sensitivity of 69%
      for detection of clinically relevant metastases (71% for macrometastases) and a
      specificity of 96%, comparable to literature results for touch imprint cytology,
      a standard technique for intraoperative diagnosis. ESS has the advantage of not
      requiring a pathologist to review the tissue sample.

PMID- 20799833
TI  - Near-infrared Raman spectroscopy to detect anti-Toxoplasma gondii antibody in
      blood sera of domestic cats: quantitative analysis based on partial least-squares
      multivariate statistics.
AB  - Toxoplasmosis is an important zoonosis in public health because domestic cats are
      the main agents responsible for the transmission of this disease in Brazil. We
      investigate a method for diagnosing toxoplasmosis based on Raman spectroscopy.
      Dispersive near-infrared Raman spectra are used to quantify anti-Toxoplasma
      gondii (IgG) antibodies in blood sera from domestic cats. An 830-nm laser is used
      for sample excitation, and a dispersive spectrometer is used to detect the Raman
      scattering. A serological test is performed in all serum samples by the enzyme
      linked immunosorbent assay (ELISA) for validation. Raman spectra are taken from
      59 blood serum samples and a quantification model is implemented based on partial
      least squares (PLS) to quantify the sample's serology by Raman spectra compared
      to the results provided by the ELISA test. Based on the serological values
      provided by the Raman/PLS model, diagnostic parameters such as sensitivity,
      specificity, accuracy, positive prediction values, and negative prediction values
      are calculated to discriminate negative from positive samples, obtaining 100, 80,
      90, 83.3, and 100%, respectively. Raman spectroscopy, associated with the PLS, is
      promising as a serological assay for toxoplasmosis, enabling fast and sensitive
      diagnosis.

PMID- 20799834
TI  - Detecting resting-state functional connectivity in the language system using
      functional near-infrared spectroscopy.
AB  - Functional connectivity has become one of the important approaches to
      understanding the functional organization of the human brain. Recently,
      functional near-infrared spectroscopy (fNIRS) was demonstrated as a feasible
      method to study resting-state functional connectivity (RSFC) in the sensory and
      motor systems. However, whether such fNIRS-based RSFC can be revealed in high
      level and complex functional systems remains unknown. In the present study, the
      feasibility of such an approach is tested on the language system, of which the
      neural substrates have been well documented in the literature. After
      determination of a seed channel by a language localizer task, the correlation
      strength between the low frequency fluctuations of the fNIRS signal at the seed
      channel and those at all other channels is used to evaluate the language system
      RSFC. Our results show a significant RSFC between the left inferior frontal
      cortex and superior temporal cortex, components both associated with dominant
      language regions. Moreover, the RSFC map demonstrates left lateralization of the
      language system. In conclusion, the present study successfully utilized fNIRS
      based RSFC to study a complex and high-level neural system, and provides further
      evidence for the validity of the fNIRS-based RSFC approach.

PMID- 20799835
TI  - Fiber-optic multiphoton flow cytometry in whole blood and in vivo.
AB  - Circulating tumor cells in the bloodstream are sensitive indicators for
      metastasis and disease prognosis. Circulating cells have usually been monitored
      via extraction from blood, and more recently in vivo using free-space optics;
      however, long-term intravital monitoring of rare circulating cells remains a
      major challenge. We demonstrate the application of a two-photon-fluorescence
      optical fiber probe for the detection of cells in whole blood and in vivo. A
      double-clad fiber was used to enhance the detection sensitivity. Two-channel
      detection was employed to enable simultaneous measurement of multiple fluorescent
      markers. Because the fiber probe circumvents scattering and absorption from whole
      blood, the detected signal strength from fluorescent cells was found to be
      similar in phosphate-buffered saline (PBS) and in whole blood. The detection
      efficiency of cells labeled with the membrane-binding dye 1,1'-dioctadecyl
      3,3,3',3'-tetramethylindoldicarbocyanine, 4-chlorobenzenesulfonate (DiD) was
      demonstrated to be the same in PBS and in whole blood. A high detection
      efficiency of green fluorescent protein (GFP)-expressing cells in whole blood was
      also demonstrated. To characterize in vivo detection, DiD-labeled untransfected
      and GFP-transfected cells were injected into live mice, and the cell circulation
      dynamics was monitored in real time. The detection efficiency of GFP-expressing
      cells in vivo was consistent with that observed ex vivo in whole blood.

PMID- 20799836
TI  - New methodology to assess activity status of occlusal caries in primary teeth
      using laser fluorescence device.
AB  - An in vivo study was conducted to verify the ability of laser fluorescence (LF)
      to assess the activity status of occlusal caries in primary teeth, using
      different air-drying times. Occlusal sites (707) were examined using LF
      (DIAGNOdent) after air-drying for 3 s and 15 s, and the difference between
      readings (DIF15 s-3 s) was calculated. For concurrent validation of LF, visual
      criteria-Nyvad (NY) and Lesion Activity Assessment associated with the
      International Caries Detection and Assessment System (LAA-ICDAS)-were the
      reference standards for lesion activity. Histological exam using a pH-indicator
      dye (0.1% methyl red) was performed in 46 exfoliated/extracted teeth for
      criterion validation. LF readings and DIF15 s-3 s were compared using Kruskall
      Wallis and Mann-Whitney tests. Receiver operating characteristic analyses were
      performed and validity parameters calculated, considering the caries activity
      assessment. Using NY, active lesions (3 s: 30.0+/-29.3; 15 s: 34.2+/-30.6)
      presented higher LF readings than inactive lesions (3 s: 17.0+/-16.3; 15 s:
      19.2+/-17.3; p<0.05), different from LAA-ICDAS. Active cavitated caries resulted
      in higher LF readings (3 s: 50.3+/-3.5; 15 s: 54.7+/-30.2) than inactive
      cavitated caries (3 s: 19.9+/-16.3; 15 s: 22.8+/-16.8). Therefore, LF can
      distinguish cavitated active and inactive lesions classified by NY, but not by
      LAA-ICDAS; however, this difference might be related to the visual system rather
      than to LF. The air-drying time could be an alternative to improve the caries
      activity assessment; however, longer air-drying time is suggested to be tested
      subsequently.

PMID- 20799837
TI  - Direct detection of aptamer-thrombin binding via surface-enhanced Raman
      spectroscopy.
AB  - In this study, we exploit the sensitivity offered by surface-enhanced Raman
      scattering (SERS) for the direct detection of thrombin using the thrombin-binding
      aptamer (TBA) as molecular receptor. The technique utilizes immobilized silver
      nanoparticles that are functionalized with thiolated thrombin-specific binding
      aptamer, a 15-mer (5'-GGTTGGTGTGGTTGG-3') quadruplex forming oligonucleotide. In
      addition to the Raman vibrational bands corresponding to the aptamer and blocking
      agent, new peaks (mainly at 1140, 1540, and 1635 cm(-1)) that are characteristic
      of the protein are observed upon binding of thrombin. These spectral changes are
      not observed when the aptamer-nanoparticle assembly is exposed to a nonbinding
      protein such as bovine serum albumin (BSA). This methodology could be further
      used for the development of label-free biosensors for direct detection of
      proteins and other molecules of interest for which aptamers are available.

PMID- 20799838
TI  - Murine photoplethysmography for in vivo estimation of vascular gold nanoshell
      concentration.
AB  - There is an urgent clinical need to monitor the intravenous delivery and
      bioavailability of circulating nanoparticles used in cancer therapy. This work
      presents the use of photoplethysmography for the noninvasive real-time estimation
      of vascular gold nanoshell concentration in a murine subject. We develop a pulse
      photometer capable of accurately measuring the photoplethysmogram in mice and
      determining the ratio of pulsatile changes in optical extinction between 805 and
      940 nm, commonly referred to as R. These wavelengths are selected to correspond
      to the extinction properties of gold nanoshells. Six 30-s measurements (5 min, 2,
      4, 6, 8, 10 h) are taken under light anesthesia to observe the change in R as the
      nanoparticles clear from the circulation. Our model describes the linear fit
      (R(2)=0.85) between R and the concentration of nanoparticles measured via ex vivo
      spectrophotometric and instrumental neutron activation analysis. This
      demonstrates the utility of this technique in support of clinical nanoparticle
      therapies.

PMID- 20799839
TI  - Changes of collagen and nicotinamide adenine dinucleotide in human cancerous and
      normal prostate tissues studied using native fluorescence spectroscopy with
      selective excitation wavelength.
AB  - The fluorescence spectra of human cancerous and normal prostate tissues obtained
      by the selective excitation wavelength of 340 nm were measured. The contributions
      of principle biochemical components to tissue fluorescence spectra were
      investigated using the method of multivariate curve resolution with alternating
      least squares. The results show that there is a reduced contribution from the
      emission of collagen and increased contribution from nicotinamide adenine
      dinucleotide (NADH) in cancerous tissues as compared with normal tissue. This
      difference is attributed to the changes of relative contents of NADH and collagen
      during cancer development. This research may present a potential native biomarker
      for prostate cancer detection.

PMID- 20799840
TI  - Polarization birefringence measurements for characterizing the myocardium,
      including healthy, infarcted, and stem-cell-regenerated tissues.
AB  - Myocardial infarction leads to structural remodeling of the myocardium, in
      particular to the loss of cardiomyocytes due to necrosis and an increase in
      collagen with scar formation. Stem cell regenerative treatments have been shown
      to alter this remodeling process, resulting in improved cardiac function. As
      healthy myocardial tissue is highly fibrous and anisotropic, it exhibits optical
      linear birefringence due to the different refractive indices parallel and
      perpendicular to the fibers. Accordingly, changes in myocardial structure
      associated with infarction and treatment-induced remodeling will alter the
      anisotropy exhibited by the tissue. Polarization-based linear birefringence is
      measured on the myocardium of adult rat hearts after myocardial infarction and
      compared with hearts that had received mesenchymal stem cell treatment. Both
      point measurement and imaging data show a decrease in birefringence in the region
      of infarction, with a partial rebound back toward the healthy values following
      regenerative treatment with stem cells. These results demonstrate the ability of
      optical polarimetry to characterize the micro-organizational state of the
      myocardium via its measured anisotropy, and the potential of this approach for
      monitoring regenerative treatments of myocardial infarction.

PMID- 20799841
TI  - Cell deformation cytometry using diode-bar optical stretchers.
AB  - The measurement of cell elastic parameters using optical forces has great
      potential as a reagent-free method for cell classification, identification of
      phenotype, and detection of disease; however, the low throughput associated with
      the sequential isolation and probing of individual cells has significantly
      limited its utility and application. We demonstrate a single-beam, high
      throughput method where optical forces are applied anisotropically to stretch
      swollen erythrocytes in microfluidic flow. We also present numerical simulations
      of model spherical elastic cells subjected to optical forces and show that dual,
      opposing optical traps are not required and that even a single linear trap can
      induce cell stretching, greatly simplifying experimental implementation. Last, we
      demonstrate how the elastic modulus of the cell can be determined from
      experimental measurements of the equilibrium deformation. This new optical
      approach has the potential to be readily integrated with other cytometric
      technologies and, with the capability of measuring cell populations, enabling
      true mechanical-property-based cell cytometry.

PMID- 20799842
TI  - Nondestructive assessment of the severity of occlusal caries lesions with near
      infrared imaging at 1310 nm.
AB  - The high transparency of dental enamel in the near-infrared (NIR) at 1310 nm can
      be exploited for imaging dental caries without the use of ionizing radiation. The
      objective of this study is to determine whether the lesion contrast derived from
      NIR imaging in both transmission and reflectance can be used to estimate lesion
      severity. Two NIR imaging detector technologies are investigated: a new Ge
      enhanced complementary metal-oxide-semiconductor (CMOS)-based NIR imaging camera,
      and an InGaAs focal plane array (FPA). Natural occlusal caries lesions are imaged
      with both cameras at 1310 nm, and the image contrast between sound and carious
      regions is calculated. After NIR imaging, teeth are sectioned and examined using
      polarized light microscopy (PLM) and transverse microradiography (TMR) to
      determine lesion severity. Lesions are then classified into four categories
      according to lesion severity. Lesion contrast increases significantly with lesion
      severity for both cameras (p<0.05). The Ge-enhanced CMOS camera equipped with the
      larger array and smaller pixels yields higher contrast values compared with the
      smaller InGaAs FPA (p<0.01). Results demonstrate that NIR lesion contrast can be
      used to estimate lesion severity.

PMID- 20799843
TI  - Adaptive spectral window sizes for extraction of diagnostic features from optical
      spectra.
AB  - We present an approach to adaptively adjust the spectral window sizes for optical
      spectra feature extraction. Previous studies extracted features from spectral
      windows of a fixed width. In our algorithm, piecewise linear regression is used
      to adaptively adjust the window sizes to find the maximum window size with
      reasonable linear fit with the spectrum. This adaptive windowing technique
      ensures the signal linearity in defined windows; hence, the adaptive windowing
      technique retains more diagnostic information while using fewer windows. This
      method was tested on a data set of diffuse reflectance spectra of oral mucosa
      lesions. Eight features were extracted from each window. We performed
      classifications using linear discriminant analysis with cross-validation. Using
      windowing techniques results in better classification performance than not using
      windowing. The area under the receiver-operating-characteristics curve for
      windowing techniques was greater than a nonwindowing technique for both normal
      versus mild dysplasia (MD) plus severe high-grade dysplasia or carcinama (SD)
      (MD+SD) and benign versus MD+SD. Although adaptive and fixed-size windowing
      perform similarly, adaptive windowing utilizes significantly fewer windows than
      fixed-size windows (number of windows per spectrum: 8 versus 16). Because
      adaptive windows retain most diagnostic information while reducing the number of
      windows needed for feature extraction, our results suggest that it isolates
      unique diagnostic features in optical spectra.

PMID- 20799845
TI  - Cavitation effect of holmium laser pulse applied to ablation of hard tissue
      underwater.
AB  - To overcome the inconsecutive drawback of shadow and schlieren photography, the
      complete dynamics of cavitation bubble oscillation or ablation products induced
      by a single holmium laser pulse [2.12 microm, 300 micros (FWHM)] transmitted in
      different core diameter (200, 400, and 600 microm) fibers is recorded by means of
      high-speed photography. Consecutive images from high-speed cameras can stand for
      the true and complete process of laser-water or laser-tissue interaction. Both
      laser pulse energy and fiber diameter determine cavitation bubble size, which
      further determines acoustic transient amplitudes. Based on the pictures taken by
      high-speed camera and scanned by an optical coherent microscopy (OCM) system, it
      is easily seen that the liquid layer at the distal end of the fiber plays an
      important role during the process of laser-tissue interaction, which can increase
      ablation efficiency, decrease heat side effects, and reduce cost.

PMID- 20799844
TI  - Application of an optical clearing agent during noninvasive laser coagulation of
      the canine vas deferens.
AB  - Development of a noninvasive vasectomy technique may eliminate male fear of
      complications and result in a more popular procedure. This study explores
      application of an optical clearing agent (OCA) to scrotal skin to reduce laser
      power necessary for successful noninvasive laser vasectomy and eliminate scrotal
      skin burns. A mixture of dimethyl sulfoxide and glycerol was noninvasively
      delivered into scrotal skin using a pneumatic jet device. Near-infrared laser
      radiation was delivered in conjunction with cryogen spray cooling to the skin
      surface in a canine model, ex vivo and in vivo. Burst pressure (BP) measurements
      were conducted to quantify strength of vas closure. A 30-min application of OCA
      improved skin transparency by 26+/-3%, reducing average power necessary for
      successful noninvasive laser vasectomy from 9.2 W without OCA (BP=291+/-31 mmHg)
      to 7.0 W with OCA (BP=292+/-19 mmHg). Control studies without OCA at 7.0 W failed
      to coagulate the vas with burst pressures (82+/-28 mmHg) significantly below
      typical ejaculation pressures (136+/-29 mmHg). Application of an OCA reduced the
      laser power necessary for successful noninvasive thermal coagulation of the vas
      by approximately 25%. This technique may result in use of a less expensive laser
      and eliminate the formation of scrotal skin burns during the procedure.

PMID- 20799846
TI  - Thermal effects of white light illumination during microsurgery: clinical pilot
      study on the application safety of surgical microscopes.
AB  - Modern operating microscopes offer high power illumination to ensure optimal
      visualization, but can also cause thermal damage. The aim of our study is to
      quantify the thermal effects in vivo and discuss conditions for safe use. In a
      pilot study on volunteers, we measured the temperature at the skin surface during
      microscope illumination, including the influence of anaesthesia and the effects
      of staining, draping, or moistening of the skin. Irradiation within the limit
      given by safety regulations (200 mW/cm(2)) results in skin surface temperature of
      43 degrees C. Higher intensities (forearm 335 mW/cm(2), back 250 mW/cm(2)) are
      tolerated, resulting in reversible hyperaemia. At a very high illumination
      intensity (750 mW/cm(2)), pain occurs within 30 s at temperatures of 46 degrees
      C+/-1 degrees C (hand and forearm), and 43 degrees C+/-2 degrees C (back),
      respectively. Anaesthesia has no distinct effect on the temperature, whereas
      staining and drapes result in much higher temperatures (>100 degrees C).
      Moistening at practicable flow rates can reduce temperature efficiently when
      combined with a light absorbing and water absorbent drape. In conclusion,
      surgeons must be aware that surgical microscope illumination without protective
      means can cause skin temperatures to rise much above pain threshold, which in our
      study serves as a (conservative) benchmark for potential damage.

PMID- 20799847
TI  - In vivo study of photosensitizer pharmacokinetics by fluorescence
      transillumination imaging.
AB  - The possibility of in vivo investigation of the pharmacokinetics of
      photosensitizers by means of fluorescence transillumination imaging is
      demonstrated. An animal is scanned in the transilluminative configuration by a
      single source and detector pair. Transillumination is chosen as an alternative
      approach to reflection imaging. In comparison with the traditional back
      reflection technique, transillumination is preferable for photosensitizer
      detection due to its higher sensitivity to deep-seated fluorophores. The
      experiments are performed on transplantable mouse cervical carcinomas using three
      drugs: photosens, alasens, and fotoditazin. For quantitative evaluation of the
      photosensitizer concentration in tumor tissue the fluorescence signal is
      calibrated using tissue phantoms. We show that the kinetics of photosensitizer
      tumor uptake obtained by transillumination imaging in vivo agree with data of
      standard ex vivo methods. The described approach enables rapid and cost-effective
      study of newly developed photosensitizers in small animals.

PMID- 20799848
TI  - Importance of pulsing illumination parameters in low-level-light therapy.
AB  - The influence of emission parameters in low-level-light therapy on cellular
      responses is not yet fully understood. This study assessed the impact of various
      light delivery modes on collagen production in human primary fibroblast cultured
      in monolayers after three treatments with red light-emitting diode illumination
      (630 nm, 8 J/cm(2)). Human type I collagen was measured in cell culture
      supernatants with procollagen type I C-peptide enzyme immunoassay. Results
      demonstrated that, 72 h post-baseline, specific microsecond pulsing patterns had
      a more favorable impact on the ability of fibroblasts to produce collagen de novo
      than comparative conditions of continuous wave, pulsed 50% duty cycle, and
      millisecond pulsing domains. The cascade of events leading to collagen production
      by red illumination may be explained by the photodissociation of nitric oxide
      from cytochrome c oxidase. Short and intermittent light delivery might enhance
      this cellular event.

PMID- 20799850
TI  - Signs of apoptosis in the pituitary, thyroid and ovaries of female rats after a
      single dose of potassium iodide.
AB  - OBJECTIVE: The aim of this work was to study the effect of a single dose of
      iodide on the expression of apoptosis mediating enzymes (caspase 32 and caspase
      8) as well as of antiapoptopic protein Bcl-2 in the anterior pituitary, thyroid
      and ovaries in rats. METHODS: A total of 24 inbred rat females of local
      laboratory strain weighing 250-300 g at the stage of diestrus and/or metestrus
      were used. Pituitary, thyroid and ovaries were dissected from the first group (8
      control rats) at the same time as these from the second group (8 rats) and third
      group (8 rats) which were given potassium iodide (KI; 4 microg/100g body weight
      by gavage) 48 hours and 120 hours prior to the sacrifice, respectively.
      Streptavidin-biotin method was used to define the expression of caspase 8 and 32
      as well as that of Bcl-2 with the aid of specific monoclonal antibodies in terms
      of the percentage of positive immunostained area (% PA). RESULTS: Histological
      examinations of endocrine glands did not show any signs of necrosis. In the
      thyroid a significant decrease of both caspases 32 and 8 was found at 120 hrs
      after KI administration. In contrast, however, in the pituitary a significant
      increase of caspase 32 appeared at 120 hrs after KI administration, although a
      considerable, but not significant increase of both caspases 32 and 8 already
      appeared after 48 hrs. In the ovaries a considerable and about the same increase
      of both caspases 32 and 8 appeared at 120 hrs after KI, though the difference was
      significant only for caspase 8. In addition, however, a considerable, but not
      significant, increase of caspase 32 at 48 hrs also appeared in the ovaries.
      CONCLUSION: The apoptotic activity was induced in the pituitary and ovaries of
      female rats by a single dose of KI, as shown by considerable increase of both the
      effectory caspase 32 and initiatory caspase 8 at 48 and 120 hrs after iodide
      administration. In contrast, however, in the thyroid any considerable changes in
      caspase 32 and caspase 8 were not observed after 48 hrs, while a significant
      decrease of both appeared after 120 hrs. Although no changes in Bcl-2 were found
      in the pituitary and thyroid, considerable and significant decrease appeared in
      the ovaries after 120 hrs.

PMID- 20799851
TI  - Fos expression in tyrosine hydroxylase containing hypothalamic neurons in CRH-KO
      mice: effect of immobilization stress.
AB  - OBJECTIVE: Little is known about the response of tyrosine hydroxylase (TH)
      containing hypothalamic neurons to stress in corticoliberine deficient (CRH-KO)
      mice. This study was aimed to extend this issue and reveal the data leading to a
      better understanding of physiological/anatomical plasticity of hypothalamic TH
      cells in response to acute immobilization stress (IMO) as well as of possible of
      CRH body deficiency contribution in the regulation of TH cells during stress. We
      examined the topographic distribution of TH protein immunolabeled perikarya in
      selected hypothalamic structures including the paraventricular (PVN), supraoptic
      (SON), periventricular (PeVN), arcuate (ArcN), dorsomedial (DMN), and
      ventromedial (VMN) nuclei and extrahypothalamic zona incerta (ZI) in CRH-KO and
      wild type (WT) mice. METHODS: The animals were perfused with fixative 120 min
      after a single IMO stress. The brains were removed, cryo-sectioned throughout the
      hypothalamus and Fos-TH co-localizations were processed immunohistochemically.
      Fos protein was visualized by diaminobenzidine (DAB) intensified with nickel
      ammonium sulphate, while TH cells were labeled only with DAB chromogen. The
      evaluation of Fos-TH co-labeled perikarya was performed with the use of
      computerized Leica light microscope and expressed as the percentage of total
      amount of TH labeled cells. RESULTS: From the qualitative point of view, the
      present data indicate similar anatomical distribution of TH immunoreactive
      perikarya in all brain structures investigated in both WT and CRH-KO mice, while
      from the quantitative point of view only TH cells in the DMN of CRH-KO mice
      showed a trend for increased activation by IMO. CONCLUSIONS: In several
      hypothalamic structures the basic population of TH neurons was not affected by
      the absence of endogenous CRH. Based on the data of this study it can also be
      assumed that despite of the presence of direct reciprocal connections between PVN
      and DMN neurons, PVN CRH neurons possibly are not participating in the regulation
      of TH neurons in the DMN during IMO stress. KEYWORDS: Hypothalamic nuclei - Fos
      immunohistochemistry - Tyrosine hydroxylase - Immobilization stress - CRH
      knockout mice.

PMID- 20799852
TI  - Interrelationship of endocrine glands under thermal stress: effect of exogenous
      glucocorticoids on mineral, enzyme, thyroid hormone profiles and phagocytosis
      index of Indian goats.
AB  - OBJECTIVE: The purpose of the investigation was to examine the pineal-adrenal
      thyroid-immune axis in female goats under short-term heat stress. The study was
      conducted to observe the influence of glucocorticoids on biochemical, endocrine
      profile and non-specific immune response in propranolol treated goats. METHODS:
      Melatonin and glucocorticoid secretions and several other endocrine and
      biochemical blood parameters reflecting the animals well being were determined
      over a one week period after goats had been exposed to 40 degrees C and 60%
      relative humidity for 17 days. Chemical pinealectomy was achieved using
      propranolol followed by exogenous hydrocortisone treatment. This treatment
      continued from day 11 to day 17 of the study. Blood samples were drawn on day 10
      to assess heat stress effect and twice daily after each treatment from day 11 to
      17 to find the effect of hydrocortisone on various parameters studied. RESULTS:
      Thermal stress significantly (P <or= 0.05) affected the levels of plasma calcium,
      ACP, ALP, T3, T4 and phagocytosis index. Chemical pinealectomy significantly (P
      <or= 0.05) affected plasma levels of the parameters studied and these could be
      significantly (P <or= 0.05) counteracted by administration of hydrocortisone to
      varying levels. Chemical pinealectomy aggravated thermal stress; although
      administration of hydrocortisone could ameliorate the condition. CONCLUSIONS: The
      data generated from the study help us to understand the functional relationship
      between pineal, adrenal and immune system, and how this relationship modifies the
      biochemical, endocrine and non-specific immune response for the well being of the
      goats under thermal stress.

PMID- 20799853
TI  - Polychlorinated biphenyls and testosterone: age and congener related correlation
      approach in heavily exposed males.
AB  - OBJECTIVE: It was aimed to evaluate some fundamental correlations of 15
      individual PCB congeners and their sum with serum testosterone level in highly
      and long-term exposed males with special respect to minimize the interfering
      effect of age. METHODS: A total of 834 males from eastern Slovakia (age range of
      21-78 years; median, 75th and 90th percentile of 48, 54 and 58 years,
      respectively) were examined consisting of 432 males from highly polluted area and
      402 males from the area of background pollution. In all of them the serum level
      of 15 polychlorinated biphenyl congeners (PCBs), hexachlorobenzene (HCB) and
      dichlorodiethyl-dichloroethylene (DDE) was measured by gas chomatography/mass
      spectrometry and total testosterone in serum was measured with the aid of
      electrochemiluminiscent immunoassay. Pearson's correlation coefficients for each
      individual PCB congener as well as for Sigma15PCBs with testosterone were
      assessed in the cohort of all 834 males and also in the cohort of 444 males with
      age range of 41-55 years in which any significant negative influence of age on
      testosterone level has not been found and thus the interfering effect of aging on
      that level was apparently minimized. RESULTS: In the cohort of 834 males with
      high level of Sigma15PCBs (median = 885; range = 211-77,084; 5% - 95% = 377 -
      4051 ng/g lipid) and highly significant negative correlation with age (r= 0.303;
      p<0.000) a significant negative correlation (p<0.05) with testosterone has been
      observed only for two mono-ortho-congeners (CB-105 and -118). However, in the
      cohort of 444 males aged 41-55 years any significant correlation for individual
      PCB congeners and for Sigma15PCBs with testosterone did not appear. CONCLUSION:
      In a large cohort of highly exposed males with minimized interfering effect of
      age any significant correlations between 15 PCB congeners analyzed and total
      testosterone were not found.

PMID- 20799854
TI  - Problems of metabolic syndrome diagnostics in children.
AB  - OBJECTIVE: Increasing prevalence of exogenous obesity in children appears
      possibly related to changes in their lipid and carbohydrate metabolism resulting
      from insulin resistance which, together with obesity and arterial hypertension,
      are among the components of metabolic syndrome. The aim of this study was to
      evaluate the age related incidence of obesity complications and the prevalence of
      metabolic syndrome in children according to the latest criteria. METHODS: A total
      of 98 obese children were divided in two age groups (5 to 10 and 10 to 16 years).
      In all patients the BMI was calculated, standard deviation score of BMI (SDS BMI)
      was estimated according to the data by anthropometric surveys Slovakia and
      obesity was defined as SDS BMI >2 which is equal to 97th percentile for the
      appropriate age and gender. Blood pressure >95th percentile for the appropriate
      gender, age and body was classified as hypertension. Fasting glycemia, total and
      HDL cholesterol and triglycerides were determined in serum and oral glucose
      tolerance test was performed. Insulin resistance was classified according to HOMA
      index. RESULTS: Among 21 children less than 10 years of age lower HOMA values and
      no impaired glucose tolerance appeared, but hypercholesterolemia was found in 8
      cases (38.1 %). Among 77 patients aged 10 to 16 years increased frequency of
      cases was found with insulin resistance (37.7 %), increased triglycerides (53.3
      %), decreased HDL cholesterol (54.4 %) and impaired glucose tolerance (7.8 %). In
      this group 32.5 % of children showed metabolic syndrome based on modified IDF
      criteria, while such prevalence rose to 39.0 % if borderline criteria for blood
      pressure were used. CONCLUSION: The treatment of referred pathological states
      requires lifestyle changes and follow up at the specialized clinic.

PMID- 20799855
TI  - Pineal-adrenal interactions in domestic male pigeon exposed to variable circadian
      light regimes and exogenous melatonin.
AB  - OBJECTIVE: This study was aimed to see the histophysiological changes of the
      pineal and adrenal glands under altered photoperiodic conditions due to the
      administration of melatonin in the male domestic pigeon, Columba livia Gmelin.
      METHODS: Young adult male domestic pigeons were exposed to long photoperiod (LP;
      20 hr light: 4 hr dark), short photoperiod (SP; 4 hr light: 20 hr dark) exogenous
      melatonin (MEL; 20 microg/100 g body weight/day) was administered for 60 days in
      the primary breeding and regressive phase. At the end of experiment, adrenal and
      pineal glands were quickly dissected and processed for histology, ultrastructure
      study, biochemical, histochemical and immunohistochemical analysis. RESULTS: In
      the primary breeding phase, the number of mitochondria and rough endoplasmic
      reticulum were increased in the adrenal gland in MEL-LP group, while lipid
      granules were also increased in the subcapsular zone. In MEL-SP treated group,
      however, the number of mitochondria decreased. Pinealocytes were increased in
      size and well-developed Golgi complexes were present near the cell nucleus after
      induction with MEL-LP treatment during the primary breeding phase. No remarkable
      changes were noticed in the number of mitochondria. In the regressive phase-I,
      the adrenocortical cytoplasm showed similar morphological features both in MEL-LP
      treatment and control groups. In pinealocytes, few rough endoplasmic reticulum
      and lipid droplets and moderate number of mitochondria were present. In MEL-SP
      treatment, increased number of mitochondria in the adrenocortical cells and
      decreased nuclear diameter of the pinealocytes were noticed. Few mitochondria
      were observed within the pinealocyte cytoplasm. Side chain cleavage enzyme
      (immunocytochemical) activity was increased in the subcapsular zone in MEL-LP
      treated group. CONCLUSIONS: The present data indicates that the changes in pineal
      and adrenocortical tissue histophysiology might be due to melatonin rhythm and
      light/dark regime which act as a modulator in the male domestic pigeon.

PMID- 20799857
TI  - Investigating shunt function using continuous intracranial pressure monitoring in
      adults: single center experience.
AB  - OBJECT: Managing symptomatic ventriculoperitoneal shunts with no clear evidence
      of shunt malfunction either clinically or radiologically can be a difficult task.
      The aim of this study was to assess intracranial pressure (ICP) monitoring as a
      method of investigating shunt function. METHODS: The authors performed a
      retrospective analysis of 38 continuous ICP monitoring procedures done in
      patients with ventriculoperitoneal shunts and suspected shunt malfunction.
      RESULTS: Thirty-eight procedures were performed in 31 patients between January
      2005 and October 2008. Sixteen recordings were normal, 6 revealed overdrainage or
      low pressure, 11 indicated underdrainage or high pressure, and 5 showed variable
      shunt function. Based on the findings after 20 procedures (53%), patients were
      treated conservatively: 4 by readjusting the valve setting and 16 by referral to
      the headache neurologist for medical treatment. Forty-five percent of the
      conservatively treated patients improved. Surgical exploration was undertaken
      following 18 procedures (47%); 72% of the surgically treated patients improved.
      CONCLUSIONS: Continuous ICP monitoring using an intraparenchymal probe is a safe
      and effective method of investigating adult hydrocephalus.

PMID- 20799856
TI  - MicroRNA-1 regulates smooth muscle cell differentiation by repressing Kruppel
      like factor 4.
AB  - The role of microRNA-1 (miR-1) has been studied in cardiac and skeletal muscle
      differentiation. However, it remains unexplored in vascular smooth muscle cells
      (SMCs) differentiation. The aim of this study was to uncover novel targets of and
      shed light on the function of miR-1 in the context of embryonic stem cell (ESC)
      differentiation of SMCs in vitro. miR-1 expression is steadily increased during
      differentiation of mouse ESC to SMCs. Loss-of-function approaches using miR-1
      inhibitors uncovered that miR-1 is required for SMC lineage differentiation in
      ESC-derived SMC cultures, as evidenced by downregulation of SMC-specific markers
      and decrease of derived SMC population. In addition, bioinformatics analysis
      unveiled a miR-1 binding site on the Kruppel-like factor 4 (KLF4) 3' untranslated
      region (3'UTR), in a region that is highly conserved across species.
      Consistently, miR-1 mimic reduced KLF4 3'UTR luciferase activity, which can be
      rescued by mutating the miR-1 binding site on the KLF4 3'UTR in the reporter
      construct. Additionally, repression of the miR-1 expression by miR-1 inhibitor
      can reverse KLF4 downregulation during ESC-SMC differentiation, which
      subsequently inhibits SMC differentiation. We conclude that miR-1 plays a
      critical role in the determination of SMC fate during retinoid acid-induced
      ESC/SMC differentiation, which may indicate that miR-1 has a role to promote SMC
      differentiation.

PMID- 20799858
TI  - En bloc temporal bone resection using a diamond threadwire saw for malignant
      tumors.
AB  - The purpose of this study is to describe a new technique for en bloc temporal
      bone resection using a diamond threadwire saw (T-saw) as an alternative to
      cutting the temporal bone with an osteotome. This technique has been performed in
      10 patients with external auditory canal and middle ear cancers without any
      injury to the internal carotid artery or jugular vein. The authors conclude that
      the use of a diamond threadwire saw after transposing the internal carotid artery
      anteriorly is a safe, simple, and reliable technique for en bloc temporal bone
      resection.

PMID- 20799859
TI  - Simultaneous measurements of intracranial pressure parameters in the epidural
      space and in brain parenchyma in patients with hydrocephalus.
AB  - OBJECT: In this study, the authors compare simultaneous measurements of static
      and pulsatile pressure parameters in the epidural space and brain parenchyma of
      hydrocephalic patients. METHODS: Simultaneous intracranial pressure (ICP) signals
      from the epidural space (ICPEPI) and the brain parenchyma (ICPPAR) were compared
      in 12 patients undergoing continuous ICP monitoring as part of their diagnostic
      workup for hydrocephalus. The static ICP was characterized by mean ICP and the
      frequency of B waves quantified in the time domain, while the pulsatile ICP was
      determined from the cardiac beat-induced single ICP waves and expressed by the
      ICP pulse pressure amplitude (dP) and latency (dT; that is, rise time). RESULTS:
      The 12 patients underwent a median of 22.5 hours (range 5.9-24.8 hours) of ICP
      monitoring. Considering the total recording period of each patient, the mean ICP
      (static ICP) differed between the 2 compartments by >=5 mm Hg in 8 patients (67%)
      and by >=10 mm Hg in 4 patients (33%). In contrast, for every patient the ICP
      pulse pressure readings from the 2 compartments showed near-identical results.
      Consequently, when sorting patients to shunt/no shunt treatment according to
      pulsatile ICP values, selection was independent of sensor placement. The
      frequency of B waves also compared well between the 2 compartments. CONCLUSIONS:
      The pulsatile ICP is measured with equal confidence from the ICPEPI and ICPPAR
      signals. When using the pulsatile ICP for evaluation of hydrocephalic patients,
      valid measurements may thus be obtained from pressure monitoring in the epidural
      space. Recorded differences in the mean ICP between the epidural space and the
      brain parenchyma are best explained by differences in the zero setting of
      different sensors.

PMID- 20799860
TI  - Regeneration of the transected rat sciatic nerve after suturing or adhesion with
      cyanoacrylate glue.
AB  - OBJECT: Traditional treatment of transected peripheral nerves has been by
      suturing the nerve ends to each other. Because this approach is not widely
      available and is technically demanding, the authors evaluated an easier method
      for end-to-end anastomosis using cyanoacrylate-based glue. METHODS: The authors
      used a rat sciatic nerve model. The sciatic nerve was transected in one hind limb
      in each of 40 rats. In 20 rats, end-to-end anastomosis was performed with
      suturing, while in the other 20 it was performed using only cyanoacrylate glue.
      The outcome variables were incapacitance test results; the functional sciatic
      index; somatosensory evoked potentials; axon counts and sizes at the proximal,
      anastomotic, and distal levels; local adhesions; and automutilation injuries.
      Outcomes were measured in a manner blinded to the anastomotic technique. RESULTS:
      Only the somatosensory evoked potentials and degree of local adhesions were
      significantly better in the Suture Group than in the Glue Group. With respect to
      the remaining outcomes (automutilation injuries, counts of large and medium axons
      combined, and counts of small axons), either the results were significantly
      better in the Glue Group or the between-groups difference was not statistically
      significant. There were no consistent significant correlations between the
      various outcome measures. CONCLUSIONS: Using cyanoacrylate-based glue for
      microanastomosis of cut nerves appears to be as effective as microsuturing the
      nerve ends. Despite more local adhesions in the glued nerves, most functional
      outcomes were not influenced by the anastomotic technique. Validation of these
      findings awaits studies of larger groups of animals.

PMID- 20799861
TI  - Transsphenoidal resection of 82 Rathke cleft cysts: limited value of alcohol
      cauterization in reducing recurrence rates.
AB  - OBJECT: The aim of this study was to report the results of a large clinical
      series of patients with symptomatic Rathke cleft cysts (RCCs) who underwent
      resection by a single neurosurgeon using intraoperative alcohol cauterization,
      and to review any possible differences in recurrence rates in those treated with
      this chemically ablative technique. METHODS: The authors performed a
      retrospective database review of 82 patients (age range 10-74 years) with
      symptomatic RCCs who underwent surgery between 1993 and 2009. RESULTS:
      Preoperative symptoms of headaches, vision disturbances, and hormone dysfunction
      were observed in 68%, 35%, and 56% of patients, respectively. All 82 patients
      underwent treatment by a single surgeon. Surgery consisting of simple cyst
      drainage followed by cyst wall biopsy without vigorous cyst wall removal was
      performed. A subset of these patients (62) received intraoperative alcohol
      instillation. Perioperative complication rates were low: CSF leakage, symptomatic
      hyponatremia, and permanent diabetes insipidus (DI) in 2%, 5%, and 0% of
      patients, respectively. Headaches and vision problems improved or resolved in 71%
      and 83% of patients, respectively. In addition, hyperprolactinemia,
      hypothyroidism, panhypopituitarism, DI, and adrenal insufficiency improved or
      resolved in 94%, 90%, 50%, 33%, and 67% of patients, respectively. Recurrence, as
      defined by enlargement of the cyst as compared with its appearance on baseline 3
      month postoperative MR imaging, was noted in 10.7% of the primary surgery group.
      There was a trend toward increased recurrence rates in the alcohol-treated
      (12.9%) versus no-alcohol treatment groups (0%), although not statistically
      significant (p = 0.20). CONCLUSIONS: This large, single-surgeon/single
      institution series of patients with symptomatic RCCs confirms that significant
      postoperative improvement in headaches, vision, and pituitary hormone dysfunction
      can be achieved via a conservative surgical approach, with low complication and
      recurrence rates. The data also demonstrate a limited role for alcohol
      cauterization in the treatment of symptomatic RCCs.

PMID- 20799862
TI  - Intraoperative mapping and monitoring of the corticospinal tracts with
      neurophysiological assessment and 3-dimensional ultrasonography-based navigation.
      Clinical article.
AB  - OBJECT: Preserving motor function is a major challenge in surgery for intraaxial
      brain tumors. Navigation systems are unreliable in predicting the location of the
      corticospinal tracts (CSTs) because of brain shift and the inability of current
      intraoperative systems to produce reliable diffusion tensor imaging data. The
      authors describe their experience with elaborate neurophysiological assessment
      and tractography-based navigation, corrected in real time by 3D intraoperative
      ultrasonography (IOUS) to identify motor pathways during subcortical tumor
      resection. METHODS: A retrospective analysis was conducted in 55 patients
      undergoing resection of tumors located within or in proximity to the CSTs at the
      authors' institution between November 2007 and June 2009. Corticospinal tract
      tractography was coregistered to surgical navigation-derived images in 42
      patients. Direct cortical-stimulated motor evoked potentials (dcMEPs) and
      subcortical-stimulated MEPs (scrtMEPs) were recorded intraoperatively to assess
      function and estimate the distance from the CSTs. Intraoperative ultrasonography
      updated the navigation imaging and estimated resection proximity to the CSTs.
      Preoperative clinical motor function was compared with postoperative outcome at
      several time points and correlated with incidences of intraoperative dcMEP alarm
      and low scrtMEP values. RESULTS: The threshold level needed to elicit scrtMEPs
      was plotted against the distance to the CSTs based on diffusion tensor imaging
      tractography after brain shift compensation with 3D IOUS, generating a trend line
      that demonstrated a linear order between these variables, and a relationship of
      0.97 mA for every 1 mm of brain tissue distance from the CSTs. Clinically, 39
      (71%) of 55 patients had no postoperative deficits, and 9 of the remaining 16
      improved to baseline function within 1 month. Seven patients had varying degrees
      of permanent motor deficits. Subcortical stimulation was applied in 45 of the
      procedures. The status of 32 patients did not deteriorate postoperatively (stable
      or improved motor status): 27 of them (84%) displayed minimum scrtMEP thresholds
      > 7 mA. Six patients who experienced postoperative deterioration quickly
      recovered (within 5 days) and displayed minimum scrtMEP thresholds > 6.8 mA. Five
      of the 7 patients who had late (> 5 days postoperatively) or no recovery had
      minimal scrtMEP thresholds < 3 mA. An scrtMEP threshold of 3 mA was found to be
      the cutoff point below which irreversible disruption of CST integrity may be
      anticipated (sensitivity 83%, specificity 95%). CONCLUSIONS: Combining elaborate
      neurophysiological assessment, tractography-based neuronavigation, and updated
      IOUS images provided accurate localization of the CSTs and enabled the safe
      resection of tumors approximating these tracts. This is the first attempt to
      evaluate the distance from the CSTs using the threshold of subcortical monopolar
      stimulation with real-time IOUS for the correction of brain shift. The linear
      correlation between the distance to the CSTs and the threshold of subcortical
      stimulation producing a motor response provides an intraoperative technique to
      better preserve motor function.

PMID- 20799863
TI  - Gamma Knife radiosurgery for larger-volume vestibular schwannomas. Clinical
      article.
AB  - OBJECT: Stereotactic radiosurgery (SRS) is an important management option for
      patients with small- and medium-sized vestibular schwannomas. To assess the
      potential role of SRS in larger tumors, the authors reviewed their recent
      experience. METHODS: Between 1994 and 2008, 65 patients with vestibular
      schwannomas between 3 and 4 cm in one extracanalicular maximum diameter (median
      tumor volume 9 ml) underwent Gamma Knife surgery. Seventeen patients (26%) had
      previously undergone resection. RESULTS: The median follow-up duration was 36
      months (range 1-146 months). At the first planned imaging follow-up at 6 months,
      5 tumors (8%) were slightly expanded, 53 (82%) were stable in size, and 7 (11%)
      were smaller. Two patients (3%) underwent resection within 6 months due to
      progressive symptoms. Two years later, with 63 tumors overall after the 2 post
      SRS resections, 16 tumors (25%) had a volume reduction of more than 50%, 22 (35%)
      tumors had a volume reduction of 10-50%, 18 (29%) were stable in volume (volume
      change < 10%), and 7 (11%) had larger volumes (5 of the 7 patients underwent
      resection and 1 of the 7 underwent repeat SRS). Eighteen (82%) of 22 patients
      with serviceable hearing before SRS still had serviceable hearing after SRS more
      than 2 years later. Three patients (5%) developed symptomatic hydrocephalus and
      underwent placement of a ventriculoperitoneal shunt. In 4 patients (6%)
      trigeminal sensory dysfunction developed, and in 1 patient (2%) mild facial
      weakness (House-Brackmann Grade II) developed after SRS. In univariate analysis,
      patients who had a previous resection (p = 0.010), those with a tumor volume
      exceeding 10 ml (p = 0.05), and those with Koos Grade 4 tumors (p = 0.02) had
      less likelihood of tumor control after SRS. CONCLUSIONS: Although microsurgical
      resection remains the primary management choice in patients with low
      comorbidities, most vestibular schwannomas with a maximum diameter less than 4 cm
      and without significant mass effect can be managed satisfactorily with Gamma
      Knife radiosurgery.

PMID- 20799864
TI  - The new role of microRNAs in cancer.

PMID- 20799867
TI  - Combretastatin A4 phosphate: a novel vascular disrupting agent.
AB  - Combretastatin A4 phosphate (CA4P) is the lead compound of a relatively new class
      of agents termed vascular disrupting agents that target existing tumor blood
      vessels. Rapid tumor blood flow shutdown has been demonstrated in preclinical
      models and patients by various techniques such as dynamic contrast-enhanced MRI,
      perfusion computed tomography and PET scans following CA4P infusion. CA4P
      typically induces rapid tumor necrosis in the center of the tumor and leaves a
      rim of viable cells in the periphery. In oncology, CA4P does not appear to be
      that active by itself, but may be more efficacious when combined with
      chemotherapy, antiangiogenic therapy and radiation therapy. Studies are currently
      underway, which combine CA4P with antiangiogenic agents. Side effects have
      included hypertension, tumor pain and occasional cardiovascular toxicity, without
      any significant myelosuppression or disabling systemic symptoms. The utility of
      CA4P for conditions other than cancer, which involves neovascularization such as
      macular degeneration, is also being explored.

PMID- 20799866
TI  - Forodesine: review of preclinical and clinical data.
AB  - Purine nucleoside phosphorylase (PNP) is an important catalytic enzyme in the
      purine salvage pathway; its deficiency is associated with T-cell lymphopenia and
      with humoral deficiency. This clinical observation led to the investigation of
      PNP inhibitors and their possible clinical application in the management of
      hematologic malignancies, notably those of T-cell lineage. Forodesine is the most
      potent of the PNP inhibitors. Its effect appears to be linked to increased 2 
      deoxyguanosine levels in plasma, which in turn is converted to 2 -deoxyguanosine
      triphosphate in target cells and disrupts DNA synthesis. Several preclinical
      studies have shown forodesine's effect against lymphocytes in vitro and in vivo,
      and these findings have led to several Phase I/II studies in patients with
      lymphoid neoplasms. Early clinical trials show that forodesine has promise as a
      single agent for the treatment of relapsed/refractory hematologic malignancies,
      and combination therapies might be warranted to improve clinical results.

PMID- 20799869
TI  - WT1 as a substrate of HtrA2: a potential pathway for therapeutic targeting by
      HtrA proteases.

PMID- 20799868
TI  - New concepts in organ site research on medulloblastoma: genetics and genomics.
AB  - Medulloblastoma is the most common solid tumor in childhood, developing in the
      cerebellum, a hindbrain structure with origins from two distinct germinal zones.
      Therefore, medulloblastoma tumors show a diversity of signaling abnormalities and
      stem cell biologies. Sonic Hedgehog and Wnt pathways drive a substantial fraction
      of tumors; however, genetic pathways underlying the most aggressive subset of
      these tumors remain uncharted. The speakers of this session discussed the genetic
      diversity of both tumors and metastases, including forward genetic screens,
      molecular classifications and stem cell biology. They also addressed novel
      signaling pathways, mouse models and biomarkers, and clinical progress in
      targeting inappropriate activation of Shh signaling.

PMID- 20799870
TI  - Effect of perioperative opioids on cancer recurrence: a hypothesis.
AB  - The possibility that anesthetic drugs can influence cancer recurrence rate is a
      subject of recent interest. Based on early in vitro data demonstrating opiates on
      breast cancer xenografts and two recent epidemiologic studies suggesting
      differences in recurrence rates in both breast and prostate cancer contingents
      dependent on whether patients received a combined regional-general anesthetic or
      a general anesthetic with opioid analgesia, there has been recent interest in the
      role of the micro-opioid receptor (MOR) in angiogenesis and oncogenic signaling.
      We recently demonstrated that morphine causes reciprocal transactivation of the
      MOR and VEGF receptors and that MOR-knockout mice do not develop significant
      tumors when injected with lung cancer cells as do their wild-type controls.
      Furthermore, infusion of the peripheral MOR antagonist methylnaltrexone markedly
      attenuates tumor growth in experimental mouse models. These experimental data
      support the hypothesis that opioids affect tumor progression and suggest the MOR
      as a potential target for chemotherapeutic drugs.

PMID- 20799871
TI  - An update on indications for treatment of solid hepatic neoplasms in noncirrhotic
      liver.
AB  - During recent years, we have experienced an increased detection of previously
      unsuspected liver masses in otherwise asymptomatic patients owing to the
      widespread application of imaging techniques. Regardless of the malignant or
      cystic tissues, a remarkable percentage of these masses are represented by benign
      solid neoplasms. Treatment of benign liver tumors still represents a major
      concern in the hepatic surgery field. Indications for surgery have remained
      unchanged for many years, but the laparoscopic approach could determine in some
      cases a broadening of indications, which may result in overtreatment. In this
      article, the main surgical indication for hepatic hemangioma, focal nodular
      hyperplasia and hepatocellular adenoma are discussed with regard to the most
      recent advancements in literature. In addition, a separate section deals with the
      role of laparoscopy in the treatment of benign liver neoplasms.

PMID- 20799872
TI  - Potential role of PI3K inhibitors in the treatment of breast cancer.
AB  - In recent years, we have witnessed advances in the understanding of molecular
      events that lead to breast cancer. This knowledge allowed, among other things,
      the development of novel therapies that target critical pathways involved in this
      disease. One of these pathways is the PI3K pathway, whose signaling axis has
      implications on cancer cell growth, survival, motility and metabolism. In the
      present review, the potential role of PI3K inhibitors in the treatment of breast
      cancer is discussed. The fast pace of development of these drugs urges the
      discussion on the advantages and pitfalls of their application and impact in the
      future therapy of breast cancer.

PMID- 20799873
TI  - Color Doppler ultrasonography for treatment response prediction and evaluation in
      breast cancer.
AB  - Primary systemic therapy is a well-established modality of treatment in locally
      advanced breast cancer. Assessment of tumor response to chemotherapy not only
      helps in assessing the efficacy of the regimen used but also predicts the overall
      outcome of the patient. The tumor vascularity is a surrogate marker of tumor
      burden and this can be readily assessed by color Doppler ultrasound using various
      indices (resistivity index, pulsatility index and maximum flow velocity). The pre
      and post-chemotherapy indices can be compared with in order assess the response
      to chemotherapy. Among various imaging modalities, MRI and PET have the highest
      sensitivity in detecting the tumor response, but they are not cost effective.
      Color Doppler ultrasound is a promising alternative for tumor response assessment
      owing to its availability, reproducibility and cost-effectiveness.

PMID- 20799874
TI  - Assessment and significance of quality of life in women with gynecologic cancer.
AB  - In the design of randomized clinical trials, quality of life (QOL) has become an
      important component across multiple cancer types. QOL includes the measurement of
      patient-reported outcomes, mostly described as the physical, social, emotional
      and functional wellbeing of the patient. These realms of wellbeing are reported
      by the patient themself and are thought to be a subjective measurement of
      response to treatment and/or treatment outcomes. Therapeutic interventions such
      as chemotherapy and/or radiation can thus be monitored from a patient
      perspective. In addition, while researchers and oncologists may recognize the
      futility of advanced and/or recurrent cancer therapy in the setting of reduced
      QOL, patients may have difficulty with discontinuing therapy. QOL research adds
      to the literature by introducing a patient perspective into the decision to treat
      aggressively. Specifically, in gynecologic cancers, there is a wide range of
      outcomes and patient characteristics to be considered. All three cancer settings 
      endometrial, cervical and ovarian - are remarkable in the QOL literature as this
      is a relatively new field with room to create interventions targeted towards
      improving QOL in often challenging clinical and life situations.

PMID- 20799875
TI  - Sexually transmitted infections and risk of prostate cancer: review of historical
      and emerging hypotheses.
AB  - Since the early 1950s when sexually transmitted infections (STIs) were first
      proposed as a possible risk factor for prostate cancer, numerous epidemiologic
      studies have been conducted. Initially, these studies were primarily small case
      control studies with retrospective, self-reported assessments of a narrow range
      of STIs, typically either any STIs, or gonorrhea and syphilis. However, as new
      STIs have been discovered/recognized, new and better tests to detect histories of
      STIs have been developed, and new resources for prostate cancer research have
      been created, epidemiologic studies have expanded to include a wide range of
      STIs, and have moved towards more rigorous, prospective study designs and
      serological assessment of STI histories. The results of these studies are
      reviewed and discussed, as well as possible new avenues of research, such as
      Trichomonas vaginalis infection and infections not typically considered to be
      sexually transmitted.

PMID- 20799876
TI  - Modern approach to metabolic rehabilitation of cancer patients: biguanides
      (phenformin and metformin) and beyond.
AB  - Comparing the experience accumulated for more than 40 years in the Laboratory of
      Endocrinology of Petrov Institute of Oncology (St Petersburg, Russia) with
      similar approaches practiced elsewhere, evidence supports the reasonability of
      metabolic rehabilitation of patients suffering from breast cancer or other
      hormone-dependent malignancies. The primary objective of such approaches is to
      improve treatment results by ameliorating hormonal-metabolic disturbances,
      including excess body fat, glucose intolerance, insulin resistance and
      manifestations of endocrine-genotoxic switchings, and modify tissue and cellular
      targets or mechanisms related or nondirectly related to the aforementioned
      disturbances. The relevant measures may be categorized as pharmacological
      (antidiabetic biguanides exemplified with metformin being most popular but not
      exclusive) and nonpharmacological (rational nutrition, moderate physical activity
      and so forth) and used separately or in different combinations.

PMID- 20799877
TI  - Radiometallated peptides targeting guanylate cyclase C and the urokinase-type
      plasminogen activator receptor.
AB  - Research is currently underway worldwide into the development of receptor
      specific radiopharmaceuticals for the imaging and treatment of cancer. The
      successful clinical development of radiolabeled somatostatin analogs for imaging
      and treatment of cancers overexpressing somatostatin receptors has catalyzed
      further preclinical investigation of other radiolabeled peptides for molecular
      imaging and peptide-receptor radiotherapy, including such well-studied peptide
      vectors as cholecystokinin, neurotensin, bombesin and RGD peptides. Within this
      larger context, this article will focus on the current status of two more recent
      additions to the list of molecular imaging targets - guanylate cyclase C, a
      specific marker for colorectal cancer, and the urokinase plasminogen activator
      receptor, a cell-surface receptor overexpressed in diverse cancer types.

PMID- 20799878
TI  - Early oncology clinical trial design in the era of molecular-targeted agents.
AB  - The introduction of molecularly targeted agents has changed the concept of drug
      development. The field has evolved over the last decade and therapeutic drugs are
      now being rationally designed to affect specific intracellular or extracellular
      pathways that are thought to be important for cancer progression. Traditionally,
      toxicity has been the primary end point for dose definition and escalation;
      however, novel targeted compounds are characterized by the lack of significant
      clinical toxicity compared with conventional chemotherapy. Alternative trial
      designs and pharmacodynamic-driven biomarkers that assess drug-target effect and
      allow demonstration of proof-of-concept for intended target modulation and
      achievement of desired biological effects have emerged to guide dose selection.
      This must be facilitated by validated preclinical tumor models and biomarker
      assays that are critical to aid understanding of which agents are likely to be
      beneficial in different cancer subtype patients and which biomarkers should be
      implemented into early trial design.

PMID- 20799879
TI  - Clinical characteristics and presentation of lung cancer according to race and
      place of birth.
AB  - This study compares the clinical presentation and characteristics of lung cancer
      among white and black patients according to place of birth, and correlates these
      factors to outcome. All newly diagnosed lung cancers from 2005 to 2007 in three
      tertiary medical centers were retrospectively reviewed; 767 patients were
      identified, 252 of whom were black. Age, sex, family history, place of birth,
      smoking history, insurance status, clinical stage, histology, grade of
      differentiation, symptoms, circumstance of diagnosis, treatment and outcome data
      were retrieved from medical charts. Lung cancer was diagnosed incidentally in
      28.2% of white individuals versus 12.3% in black individuals (p < 0.0001). After
      adjustment for other variables, black and white individuals have similar survival
      rates (hazard ratio: 1.3; 95% CI: 0.8-2.0). The differences in lung cancer
      survival could be related to access to care, environmental factors and the
      biology of the disease. Including place of birth in cancer outcome studies could
      help understanding the origin of health disparity.

PMID- 20799881
TI  - Cysteine-based redox switches in enzymes.
AB  - The enzymes involved in metabolism and signaling are regulated by
      posttranslational modifications that influence their catalytic activity, rates of
      turnover, and targeting to subcellular locations. Most prominent among these has
      been phosphorylation/dephosphorylation, but now a distinct class of modification
      coming to the fore is a set of versatile redox modifications of key cysteine
      residues. Here we review the chemical, structural, and regulatory aspects of such
      redox regulation of enzymes and discuss examples of how these regulatory
      modifications often work in concert with phosphorylation/dephosphorylation
      events, making redox dependence an integral part of many cell signaling
      processes. Included are the emerging roles played by peroxiredoxins, a family of
      cysteine-based peroxidases that now appear to be major players in both
      antioxidant defense and cell signaling.

PMID- 20799883
TI  - Clinical outcome of mild head injury with isolated oculomotor nerve palsy.
AB  - Isolated oculomotor nerve palsy after mild head injury is rare. Only a few case
      reports have described the clinical presentation of these patients, and clinical
      and functional outcome have not been discussed in depth. The outcome of 10
      patients with mild head injury in whom imaging studies ruled out other possible
      causes of oculomotor palsy was assessed during follow-up using the Glasgow
      Outcome Scale-Extended (GOSE). We suggest that limited eye movement is a major
      factor that negatively affects functional status after mild head injury.

PMID- 20799882
TI  - Sustained expression of vascular endothelial growth factor and angiopoietin-1
      improves blood-spinal cord barrier integrity and functional recovery after spinal
      cord injury.
AB  - Spinal cord injury (SCI) results in immediate disruption of the spinal vascular
      network, triggering an ischemic environment and initiating secondary
      degeneration. Promoting angiogenesis and vascular stability through the induction
      of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1),
      respectively, provides a possible therapeutic approach in treating SCI. We
      examined whether supplementing the injured environment with these two factors,
      which are significantly reduced following injury, has an effect on lesion size
      and functional outcome. Sustained delivery of both VEGF(165) and Ang-1 was
      realized using viral vectors based on the adeno-associated virus (AAV), which
      were injected directly into the lesion epicenter immediately after injury. Our
      results indicate that the combined treatment with VEGF and Ang-1 resulted in both
      reduced hyperintense lesion volume and vascular stabilization, as determined by
      magnetic resonance imaging (MRI). Western blot analysis indicated that the viral
      vector expression was maintained into the chronic phase of injury, and that the
      use of the AAV vectors did not exacerbate infiltration of microglia into the
      lesion epicenter. The combined treatment with AAV-VEGF and AAV-Ang-1 improved
      locomotor recovery in the chronic phase of injury. These results indicate that
      combining angiogenesis with vascular stabilization may have potential therapeutic
      applications following SCI.

PMID- 20799884
TI  - Spinal cord blood flow and blood vessel permeability measured by dynamic computed
      tomography imaging in rats after localized delivery of fibroblast growth factor.
AB  - Following spinal cord injury, profound vascular changes lead to ischemia and
      hypoxia of spinal cord tissue. Since fibroblast growth factor 2 (FGF2) has
      angiogenic effects, its delivery to the injured spinal cord may attenuate the
      tissue damage associated with ischemia. To limit systemic mitogenic effects, FGF2
      was delivered to the spinal cord via a gel of hyaluronan and methylcellulose
      (HAMC) injected into the intrathecal space, and compared to controls receiving
      HAMC alone and artificial cerebrospinal fluid (aCSF) alone. Dynamic perfusion
      computed tomography (CT) was employed for the first time in small animals to
      serially measure blood flow and permeability in the injured and uninjured spinal
      cord. Spinal cord blood flow (SCBF) and permeability-surface area (PS)
      measurements were obtained near the injury epicenter, and at two regions rostral
      to the epicenter in animals that received a 26-g clip compression injury. As
      predicted, SCBF measurements decreased and PS increased after injury. FGF2
      delivered via HAMC after injury restored SCBF towards pre-injury values in all
      regions, and increased blood flow rates at 7 days post-injury compared to pre
      injury measurements. PS was stabilized at regions rostral to the epicenter of
      injury when FGF2 was delivered with HAMC, with significantly lower values than
      aCSF controls at 7 days in the region farthest from the epicenter. Laminin
      staining for blood vessels showed a qualitative increase in vessel density after
      7 days when FGF2 was locally delivered. Additionally, permeability stains showed
      that FGF2 moderately decreased permeability at 7 days post-injury. These data
      demonstrate that localized delivery of FGF2 improves spinal cord hemodynamics
      following injury, and that perfusion CT is an important technique to serially
      measure these parameters in small animal models of spinal cord injury.

PMID- 20799885
TI  - Human primary articular chondrocytes, chondroblasts-like cells, and
      dedifferentiated chondrocytes: differences in gene, microRNA, and protein
      expression and phenotype.
AB  - In this study we have isolated human primary uncultured articular chondrocytes.
      When these cells are allowed to proliferate within their own extracellular matrix
      (ECM), they begin to produce hyaline ECM molecules similar to embryological
      chondroblasts. These cells are called chondroblast-like cells. Upon continued
      culture these cells spread onto the plastic surface and dedifferentiate. We have
      characterized these three stages of chondral cells by gene expression and
      expression of microRNAs (miRNAs) and proteins. Gene expression was quantified by
      real-time reverse transcriptase (RT) polymerase chain reaction, miRNA expression
      by miRNA arrays, and protein synthesis by extra- and intracellular flow
      cytometry. Many of the genes, miRNAs, and proteins were differentially expressed
      in the different stages of chondral cells. In the context of cellular therapy,
      expression of some genes is a cause for concern. The best source of cells for
      treatment of lesions of hyaline cartilage has not yet been identified. Adult
      chondroblast-like cells may be strong candidates. Profound understanding of how
      expression of genes and synthesis of proteins are regulated in these cells, for
      instance, by miRNAs, may reveal new strategies for improving their synthesis of
      hyaline ECM. This insight is important to be able to use these cells in the
      clinic.

PMID- 20799886
TI  - Bone formation and neovascularization mediated by mesenchymal stem cells and
      endothelial cells in critical-sized calvarial defects.
AB  - Bone represents a highly dynamic tissue whose development is strongly dependent
      on vasculogenic and angiogenic processes. Neovascularization also plays an
      important role in fracture healing and in tissue engineering applications aiming
      at restoring bone function. We have previously shown in a heterotopic
      subcutaneous implantation model of severe combined immunodeficiency (SCID) mice
      that implanted human umbilical vein endothelial cells (HUVECs) gave rise to the
      formation of a complex functional human neovasculature. In this study, we
      investigated the effect of HUVEC coimplantation on mesenchymal stem cell (MSC)
      mediated bone regeneration in an orthotopic calvarial bone defect model in
      immunocompromised mice. For this purpose, human fibrin/Matrigel-immobilized
      HUVECs and MSCs were seeded alone or in combination into scaffolds consisting of
      decalcified processed bovine cancellous bone (Tutobone) and implanted into
      calvarial critical-sized defects. Our results show that implanted HUVECs formed
      complex three-dimensional networks of perfused human neovessels that were
      stabilized by recruiting perivascular cells. Neovessel formation was considerably
      higher in the coimplantation group, suggesting that implanted MSCs supported
      HUVEC-triggered neovascularization. In addition, implanted MSCs effectively
      supported bone formation in calvarial defects. However, the HUVEC-derived
      neovasculature did not improve MSC-triggered bone regeneration in this orthotopic
      critical-sized defect model.

PMID- 20799887
TI  - Slow-release human recombinant bone morphogenetic protein-2 embedded within
      electrospun scaffolds for regeneration of bone defect: in vitro and in vivo
      evaluation.
AB  - The design of mat-like scaffolds slow-releasing bone morphogenetic protein-2 (BMP
      2) retaining bone regeneration functions has been a major challenge in tissue
      engineering. This study aimed to develop core-shell fiber scaffolds releasing BMP
      2 to support bone regeneration. BMP-2 was incorporated in an aqueous core
      solution of poly(ethylene oxide), whereas the shell solution was made of
      polycaprolactone blended with poly(ethylene glycol). This blending induced pores
      in the shell, which pronouncedly affected the movement of proteins out of the
      fibers. BMP-2 release profiles were monitored. In vitro bioactivity of BMP-2
      released from the scaffolds was assessed using human mesenchymal stem cells by
      measuring alkaline phosphatase activity. Bone regeneration capabilities were
      demonstrated by implanting the BMP-2-embedded scaffolds in rat cranial defect
      model followed by micro-computed tomography analysis. The degree of fiber's shell
      porosity, highly correlative with the slow- and fast-release patterns of BMP-2,
      were found to be dependent on the relative amount of poly(ethylene glycol) within
      the shell. In vitro assays of scaffolds manifesting the slow-release pattern have
      revealed significant (~9-fold) increase in alkaline phosphatase activity,
      compared to fast BMP-2 releasing scaffolds. Likewise, in vivo studies have
      revealed significant bone regeneration in cranial defects of scaffold implants
      with recombinant human BMP-2 with slow-release pattern.

PMID- 20799888
TI  - Three-dimensional co-cultures of osteoblasts and endothelial cells in DegraPol
      foam: histological and high-field magnetic resonance imaging analyses of pre
      engineered capillary networks in bone grafts.
AB  - Tissue engineering of bone grafts was addressed in a critical-sized model on the
      chick chorioallantoic membrane model, using DegraPol((r)) foam as scaffold
      material. The scaffolds were seeded with cultures of human osteoblasts and human
      endothelial cells, respectively, or with a co-culture of the two cell types
      (control: no cells). In vitro samples (7 days cultivation) and ex vivo
      chorioallantoic membrane model samples at incubation day 15 were analyzed by high
      field magnetic resonance imaging (MRI) and histology. The co-culture system
      performed best with respect to perfusion, as assessed by contrast-enhanced MRI
      using gadolinium-diethylene-triamine-pentaacetic acid (DTPA). The scaffold seeded
      by the co-culture supported an increased vascular ingrowth, which was confirmed
      by histological analysis. DegraPol foam is a suitable scaffold for bone tissue
      engineering and the MRI technique allows for nondestructive and quantitative
      assessment of perfusion capability during early stages of bone forming
      constructs.

PMID- 20799889
TI  - Porous poly(vinyl alcohol)-hydrogel matrix-engineered biosynthetic cartilage.
AB  - The objective of this study was to fabricate hydrogel matrix-engineered
      biosynthetic cartilage using a porous poly(vinyl alcohol) hydrogel (PVA-H) and
      articular chondrocytes. Chondrocytes were suspended in fibrin gel (FG) or saline
      carriers and injected into porous PVA-H discs and three-layered constructs (PVA-H
      between devitalized cartilage). After implantation in nude mice, PVA discs were
      explanted at 6 weeks and subjected to creep testing for a 20 h period. The three
      layered constructs were explanted at 12 weeks and subjected to tensile testing to
      determine the strength of the interface between the engineered hydrogel and
      devitalized cartilage. Histological analysis revealed PVA-H porous channels
      occupied by chondrocytes. Extracellular matrix was identified by Safranin-O and
      toluidine blue stains. Immunohistochemical analysis revealed a positive stain for
      COL II and scant staining for COL I. Creep and relaxation response of PVA-FG
      chondrocyte constructs was similar to that of native cartilage. The presence of
      cells and FG significantly enhanced the integration strength of layered
      constructs (p < 0.05). These results demonstrate that porous PVA-H in combination
      with FG and chondrocytes provides a favorable microenvironment for tissue
      engineering of articular cartilage, creating a biosynthetic construct that can
      adhere to native devitalized articular cartilage utilizing hydrogel matrix
      engineered technology.

PMID- 20799890
TI  - Three-dimensional tissue scaffolds from interbonded poly(epsilon-caprolactone)
      fibrous matrices with controlled porosity.
AB  - In this article, we report on the preparation and cell culture performance of a
      novel fibrous matrix that has an interbonded fiber architecture, excellent pore
      interconnectivity, and controlled pore size and porosity. The fibrous matrices
      were prepared by combining melt-bonding of short synthetic fibers with a template
      leaching technique. The microcomputed tomography and scanning electron microscopy
      imaging verified that the fibers in the matrix were highly bonded, forming unique
      isotropic pore architectures. The average pore size and porosity of the fibrous
      matrices were controlled by the fiber/template ratio. The matrices having the
      average pore size of 120, 207, 813, and 994 MUm, with the respective porosity of
      73%, 88%, 96%, and 97%, were investigated. The applicability of the matrix as a
      three-dimensional (3D) tissue scaffold for cell culture was demonstrated with two
      cell lines, rat skin fibroblast and Chinese hamster ovary, and the influences of
      the matrix porosity and surface area on the cell culture performance were
      examined. Both cell lines grew successfully in the matrices, but they showed
      different preferences in pore size and porosity. Compared with two-dimensional
      tissue culture plates, the cell number on 3D fibrous matrices was increased by
      97.27% for the Chinese hamster ovary cells and 49.46% for the fibroblasts after
      21 days of culture. The fibroblasts in the matrices not only grew along the fiber
      surface but also bridged among the fibers, which was much different from those on
      two-dimensional scaffolds. Such an interbonded fibrous matrix may be useful for
      developing new fiber-based 3D tissue scaffolds for various cell culture
      applications.

PMID- 20799891
TI  - Reestablishment of hope as an intervention for a patient with cystic fibrosis
      awaiting lung transplantation.
AB  - Patients with cystic fibrosis (CF) experience a progressive deterioration in
      health leading to a shortened life expectancy with concomitant psychologic
      challenges that also may require intervention. Approaches to address psychologic
      dysfunction include insight-oriented therapy, cognitive-behavioral therapy,
      biofeedback, hypnosis, massage, music therapy, relaxation, and family therapy.
      Patients who learn to use coping strategies are more likely to adhere to
      treatment, which helps improve both their physical and psychologic well-being.
      Unique stressors arise for patients awaiting lung transplant as a result of their
      advanced state of disease along with their fear of death before donor lungs
      become available. This case report demonstrates some of the psychologic struggles
      faced by a 10-year-old with CF as he awaited lung transplantation, which led to a
      loss of hope and his request for withdrawal of care. Encouraging of the patient
      to express how his life might be improved yielded changes in his management that
      restored his hopefulness, and allowed him to survive long enough to undergo
      successful lung transplantation. Thus, reestablishment of hope might be studied
      as an additional intervention to help improve the well-being of patients who are
      seriously ill.

PMID- 20799892
TI  - Functional single-nucleotide polymorphism in acetyl-CoA carboxylase ACACB gene
      promoter.
AB  - The acetyl-CoA carboxylase isoform ACC2 expressed in the liver generates malonyl
      CoA, which primarily regulates fatty acid oxidation through inhibition of the
      mitochondrial carrier carnitine palmitoyl-CoA transferase-I. Activity is
      initiated by sterol regulatory element-binding protein-1 (SREBP-1) binding to
      steroid response elements SRE in ACACB gene promoter P-II. We proposed that
      sequence variation in the promoter might affect expression. We investigated the
      effect of a single-nucleotide polymorphism -368 C/T (rs16939972) in ACACB P-II on
      activity in transfected HepG2 hepatoma cells. The T-allele construct showed
      significantly lower activity than the C-allele (p = 0.016) but only in the
      presence of SREBP-1a overexpression. Electrophoretic mobility shift assays showed
      that HepG2 nuclear proteins bound specifically to both allele probes, but with
      higher affinity to the T-allele. We tested competition for nuclear protein
      binding between the T-allele probe and unlabeled probes containing consensus
      sequences for six candidate transcription factors plus SREBP-1a. The SREBP-1a
      competitor probe had no effect on the shifted complex. GATA, c-Myb, and GR
      competitor probes abolished the complex; however, these proteins were
      undetectable in mass spectrometry of gel extracts from shifted bands. In
      conclusion, the -368 C/T single-nucleotide polymorphism in ACACB P-II binds HepG2
      nuclear proteins that affect promoter activity in an allele-specific fashion.

PMID- 20799894
TI  - The effect of community-based support services on clinical efficacy and health
      related quality of life in HIV/AIDS patients in resource-limited settings in sub
      Saharan Africa.
AB  - Antiretroviral therapy (ART) for HIV/AIDS in developing countries has been
      rapidly scaled up through directed public and private resources. Data on the
      efficacy of ART in developing countries are limited, as are operational research
      studies to determine the effect of selected nonmedical supportive care services
      on health outcomes in patients receiving ART. We report here on an investigation
      of the delivery of medical care combined with community-based supportive services
      for patients with HIV/AIDS in four resource-limited settings in sub-Saharan
      Africa, carried out between 2005 and 2007. The clinical and health-related
      quality of life (HRQOL) efficacy of ART combined with community support services
      was studied in a cohort of 377 HIV-infected patients followed for 18 months, in
      community-based clinics through patient interviews, clinical evaluations, and
      questionnaires. Patients exposed to community-based supportive services
      experienced a more rapid and greater overall increase in CD4 cell counts than
      unexposed patients. They also had higher levels of adherence, attributed
      primarily to exposure to home-based care services. In addition, patients
      receiving home-based care and/or food support services showed greater
      improvements in selected health-related QOL indicators. This report discusses the
      feasibility of effective ART in a large number of patients in resource-limited
      settings and the added value of concomitant community-based supportive care
      services.

PMID- 20799897
TI  - Infant feeding and contraceptive practices among adolescents with a high teen
      pregnancy rate: a 3-year retrospective study.
AB  - BACKGROUND: Adolescents consistently demonstrate the lowest rates of
      breastfeeding among women of reproductive age despite well-documented benefits of
      breastfeeding. In Amarillo, Texas, a medium-sized community with a perennially
      high teen pregnancy rate, we sought (1) to determine breastfeedings practices
      among adolescent females immediately after delivery and again at 6 weeks and (2)
      to identify contraceptive choices among the same teen population. METHODS: This
      was a retrospective chart review focused on adolescents between the ages of 13
      and 18 coming to a university-based obstetrical service between January 1, 2006,
      and December 31, 2008. Data on breastfeeding and contraceptive practices were
      analyzed. RESULTS: Five hundred forty-three cases were analyzed. At hospital
      discharge, 59.3% initiated breastfeeding, but this dropped to 22.2% at the 6-week
      postpartum appointment. Over 27% of all study subjects failed to appear for
      postpartum evaluation. Multiparity was the only outcome variable associated with
      failure to initiate breastfeeding. Depot-medroxyprogesterone acetate, the
      levonorgestrel intrauterine device (IUD), and combination oral contraceptives
      were the most popular contraceptive choices, but 16% elected to forego any form
      of contraception at the postpartum visit. CONCLUSIONS: Adolescent women living in
      an area of Texas with a high teen pregnancy rate reported relatively low
      breastfeeding rates immediately postpartum, with a >50% decrease in breastfeeding
      in any form by 6 weeks postpartum. A substantial number failed to initiate any
      form of contraception at the postpartum visit. These findings support the
      critical need for additional breastfeeding support and contraceptive education in
      this at-risk adolescent population.

PMID- 20799898
TI  - Cholesteryl ester transfer protein Taq1B polymorphism in an angiographically
      assessed Turkish population: no effects on coronary artery disease risk.
AB  - BACKGROUND: Taq1B polymorphism of cholesteryl ester transfer protein (CETP) is
      believed to associate with high-density lipoprotein-cholesterol (HDL-C) levels
      and may alter the susceptibility to atherosclerosis. AIM OF THE STUDY: This study
      investigated the effects of Taq1B polymorphism on HDL-C and coronary artery
      disease (CAD) risk in angiographically defined CAD patients. METHODS: One hundred
      thirty-five CAD patients and 112 healthy controls were screened for the CETP
      Taq1B genotype and plasma lipids. RESULTS: The genotype frequency of CAD patients
      and controls were similar. The HDL-C levels of all genotypes in the CAD group
      were significantly lower than the corresponding controls. Smoking and plasma
      triglycerides were the predictors of the HDL-C level in B1B1 bearers, whereas the
      subjects with a polymorphic B2 allele were affected by smoking and sex.
      CONCLUSION: CETP Taq1B polymorphism neither plays a role in determining HDL-C
      levels nor is a useful predictor of the risk of CAD.

PMID- 20799899
TI  - The essential unity of CAM.

PMID- 20799900
TI  - Chair massage for treating anxiety in patients withdrawing from psychoactive
      drugs.
AB  - CONTEXT: Therapeutic massage has been proven to be an effective,
      nonpharmacologic, alternative for managing state and trait anxiety in a variety
      of clinical situations. However, no controlled study has investigated this effect
      in an addiction treatment setting. AIM: The aim of this study was to investigate
      the effectiveness of chair massage for reducing anxiety in persons participating
      in an inpatient withdrawal management program for psychoactive drugs. DESIGN: The
      design was a randomized, controlled clinical trial conducted from June 2008 to
      January 2009. SUBJECTS: Eighty-two (82) adult patients received inpatient
      treatment for psychoactive drug withdrawal (alcohol, cocaine, and opiates).
      SETTING: This study was conducted at the Withdrawal Management Services at the
      Capital District Health Authority, Halifax, Nova Scotia. INTERVENTIONS: Subjects
      were randomly assigned to receive chair massage (n = 40) or a relaxation control
      condition (n = 42). Treatments were offered for 3 consecutive days. Standard
      counseling and pharmacologic management were also offered concurrently to
      patients in all conditions. MEASUREMENTS: The primary outcome measure was anxiety
      assessed using the Spielberger State-Trait Anxiety Inventory (STAI). State and
      trait anxiety scores were determined immediately prior to and following each
      treatment intervention. RESULTS: Analysis of STAI scores showed a significant
      reduction in state and trait anxiety for both interventions (p < 0.001). The
      magnitude in the reduction in state (p = 0.001) and trait (p = 0.045) anxiety was
      significantly greater in the chair massage group where the effect on state
      anxiety was sustained, at least in part, for 24 hours. CONCLUSIONS: Within the
      clinical context of this study, chair massage was more effective that relaxation
      control in reducing anxiety. Further investigation of chair massage as a
      potential nonpharmacologic adjunct in the management of withdrawal related
      anxiety is warranted.

PMID- 20799901
TI  - A randomized trial of nature scenery and sounds versus urban scenery and sounds
      to reduce pain in adults undergoing bone marrow aspirate and biopsy.
AB  - OBJECTIVES: Bone marrow aspiration and biopsy (BMAB) is painful when performed
      with only local anesthetic. Our objective was to determine whether viewing nature
      scenes and listening to nature sounds can reduce pain during BMAB. DESIGN: This
      was a randomized, controlled clinical trial. Adult patients undergoing outpatient
      BMAB with only local anesthetic were assigned to use either a nature scene with
      accompanying nature sounds, city scene with city sounds, or standard care. The
      primary outcome was a visual analog scale (0-10) of pain. Prespecified secondary
      analyses included categorizing pain as mild and moderate to severe and using
      multiple logistic regression to adjust for potential confounding variables.
      RESULTS: One hundred and twenty (120) subjects were enrolled: 44 in the Nature
      arm, 39 in the City arm, and 37 in the Standard Care arm. The mean pain scores,
      which were the primary outcome, were not significantly different between the
      three arms. A higher proportion in the Standard Care arm had moderate-to-severe
      pain (pain rating >=4) than in the Nature arm (78.4% versus 60.5%), though this
      was not statistically significant (p = 0.097). This difference was statistically
      significant after adjusting for differences in the operators who performed the
      procedures (odds ratio = 3.71, p = 0.02). CONCLUSIONS: We confirmed earlier
      findings showing that BMAB is poorly tolerated. While mean pain scores were not
      significantly different between the study arms, secondary analyses suggest that
      viewing a nature scene while listening to nature sounds is a safe, inexpensive
      method that may reduce pain during BMAB. This approach should be considered to
      alleviate pain during invasive procedures.

PMID- 20799902
TI  - Shared care in basic level palliative home care: organizational and interpersonal
      challenges.
AB  - BACKGROUND: Little is known about the existing barriers to cooperation among
      health professionals in basic level palliative care for terminally ill patients
      with cancer in primary health care. OBJECTIVE: The aim of this study was to
      analyze health professionals' views on interprofessional cooperation in basic
      level palliative home care for terminally ill cancer patients. METHOD: This study
      was a qualitative, descriptive study based on 7 semistructured group interviews
      conducted in the former Aarhus County, Denmark. Forty-three health professionals
      (23 family physicians, 5 chief physicians, and 15 home care nurses) were
      interviewed. RESULTS: Two main categories of problems were identified: (1) the
      organization of palliative home care (need for proactive planning from the start
      of the palliative trajectory, clear distribution of tasks, advancement of more
      efficient communication pathways, and improved accessibility to all health
      professionals) and (2) interaction between health professionals (increased
      knowledge of and respect for the competencies of other health occupations and
      individuals). CONCLUSION: The study indicates problems with respect to both the
      organization of the basic level palliative home care and the working culture
      among health professionals. The main issues: distribution of tasks, information
      exchange, availability, respect, and personal acquaintance are pivotal to improve
      the delivery of palliative home care, to training in palliative care and warrant
      future research.

PMID- 20799903
TI  - Opioid use at the end of life and survival in a Hospital at Home unit.
AB  - BACKGROUND AND SIGNIFICANCE: Although opioids are commonly used to treat pain,
      dyspnea, and other symptoms at the end of life, little information is available
      on the safety and efficacy of the use of these medications in terminally ill
      patients in the home care setting. OBJECTIVES: To explore whether high doses of
      opioids, or increasing doses, influence survival in patients with terminal cancer
      in a Hospital at Home unit. METHODOLOGY: A retrospective cohort study. Clinical
      records of 223 oncologic patients admitted to the Hospital at Home unit of
      Hospital Galdakao-Usansolo from 2003 to 2007 and who died at home were reviewed.
      Demographic variables (age and gender) as well as clinical variables at the time
      of admission (Eastern Cooperative Oncology Group Performance Status scale,
      previous intake of opioids, type of cancer, use of coadjuvant drugs) and daily
      doses of morphine during the admission were recorded. Main outcomes were the
      number of days from the maximum dose of opioids administered to death and total
      length of survival during the admission. RESULTS: Median survival from day of
      maximum dose to death was longer for patients who received higher doses of
      opioids (6 days) than those who received lower doses (2 days; p = 0.010). These
      differences disappeared after adjusting by demographic and clinical variables
      (HR, 0.86; 95% CI, 0.62-1.18 [p = 0.338]). Patients who received more than
      twofold increases in their initial doses had longer median survival (22 days)
      than those who did not (9 days; hazard ratio [HR], 0.45; 95% confidence interval
      [CI], 0.34-0.60 [p < 0.0001]); these differences persisted after adjustment.
      CONCLUSIONS: Our results suggest that the use of opioids is safe in for use in
      Hospital at Home patients with cancer and is not associated with reduced
      survival.

PMID- 20799904
TI  - Disability perspectives on health care planning and decision-making.
AB  - BACKGROUND: Despite the needs for people with disabilities to plan for times of
      serious illness in order to receive good end-of-life care and to have their
      wishes respected, this community has often been overlooked in the extensive
      research, programs, and policies regarding advance care planning and palliative
      care. This article reviews the literature addressing the significance of
      disability on health care decision-making, advance care planning, and end-of-life
      care. Special attention is provided to assessing the life values or preferences
      of persons with intellectual disability with limited decisional capacity.
      Recommendations are suggested for more inclusionary dialogue, research to better
      inform palliative care services, and new planning models for individuals with
      limited capacity.

PMID- 20799906
TI  - Fibrin glues in combination with mesenchymal stem cells to develop a tissue
      engineered cartilage substitute.
AB  - Damage of cartilage due to traumatic or pathological conditions results in
      disability and severe pain. Regenerative medicine, using tissue engineering-based
      constructs to enhance cartilage repair by mobilizing chondrogenic cells, is a
      promising approach for restoration of structure and function. Fresh fibrin (FG)
      and platelet-rich fibrin (PR-FG) glues produced by the CryoSeal((r)) FS System,
      in combination with human bone marrow-derived mesenchymal stem cells (BM-hMSCs),
      were evaluated in this study. We additionally tested the incorporation of heparin
      based delivery system (HBDS) into these scaffolds to immobilize endogenous growth
      factors as well as exogenous transforming growth factor-beta(2). Strongly, CD90+
      and CD105+ hMSCs were encapsulated into FG and PR-FG with and without HBDS.
      Encapsulation of hMSCs in PR-FG led to increased expression of collagen II gene
      at 2.5 weeks; however, no difference was observed between FG and PR-FG at 5
      weeks. The incorporation of HBDS prevented the enhancement of collagen II gene
      expression. BM-hMSCs in FG initially displayed enhanced aggrecan gene expression
      and increased accumulation of Alcian blue-positive extracellular matrix;
      incorporation of HBDS into these glues did not improve aggrecan gene expression
      and extracellular matrix accumulation. The most significant effect on cartilage
      marker gene expression and accumulation was observed after encapsulation of hMSCs
      in FG. We conclude that FG is more promising than PR-FG as a scaffold for
      chondrogenic differentiation of hMSCs; however, immobilization of growth factors
      inside these fibrin scaffolds with the HBDS system has a negative impact on this
      process. In addition, BM-hMSCs are valid and potentially superior alternatives to
      chondrocytes for tissue engineering of articular cartilage.

PMID- 20799905
TI  - Temporal exposure to chondrogenic factors modulates human mesenchymal stem cell
      chondrogenesis in hydrogels.
AB  - Tissue engineering utilizes scaffolds containing chondrogenic cells to promote
      cartilage development at a clinically relevant scale, yet there remains a limited
      understanding of the optimal conditions for inducing differentiation and matrix
      production. We investigated how cell density and temporal exposure to
      chondrogenic factors impacted chondrogenesis of human mesenchymal stem cells
      (hMSCs) encapsulated in poly(ethylene glycol) diacrylate hydrogels. We found
      maximal proteoglycan and collagen production in constructs seeded between 10 and
      25 * 10(6) cells/mL. Matrix deposition was significantly less per cell in
      constructs seeded at either higher or lower densities, indicating that paracrine
      communications may remain important despite loss of direct cell-cell contact. In
      vitro chondrogenesis of hMSCs was first accomplished using pellet cultures and a
      defined medium containing transforming growth factor (TGF)-beta1 and
      dexamethasone. The differentiation of hMSCs in hydrogels also required initial
      exposure to TGF-beta1, with no chondrogenic matrix produced in its absence. If
      TGF-beta1 was initially included for at least 7 days, its removal impacted
      collagen production per cell but also lead to an increase in cell number, such
      that total collagen deposition was equivalent to controls when TGF-beta1 was
      included for at least 3 weeks. Further, proteoglycan content per construct was
      higher at 6 weeks after removal of TGF-beta1 at any time. In contrast to TGF
      beta1, dexamethasone was not required for chondrogenesis of hMSCs in hydrogels:
      there was no difference in matrix deposition between hydrogels cultured with or
      without dexamethasone. Further, without dexamethasone, SOX9 gene expression was
      higher during early chondrogenesis and there was a significant reduction in
      collagen I deposition, suggesting that a more hyaline cartilage phenotype is
      achieved without dexamethasone. Collagen content at 6 weeks was lower if
      dexamethasone was excluded after the first 7 days, but was equivalent to control
      if dexamethasone was included for 2 weeks or longer. Proteoglycan deposition was
      unaffected by dexamethasone exclusion. These results indicate that modulating
      exposure to TGF-beta1 is beneficial for cell survival/proliferation and matrix
      production from hMSCs in hydrogels, and that not only is dexamethasone
      dispensable but also its exclusion may be advantageous for forming hyaline
      cartilage.

PMID- 20799907
TI  - Hepatic stellate cell-mediated three-dimensional hepatocyte and endothelial cell
      triculture model.
AB  - Hepatic stellate cells (HSCs) form a functional unit with endothelia and
      hepatocytes in the liver to play a pivotal role in heterotypic cellular
      communication. To investigate this role of HSCs, it is of great benefit to
      establish a triculture model that forms the functional unit from proximal layers
      of hepatocytes, HSCs, and endothelial cells (ECs). Here, we established a three
      dimensional triculture model, using a microporous membrane to create the
      functional unit. HSC behavior was controlled by the membrane pore size, which was
      critical for achieving proximal cell layers. With a specific pore size, the HSCs
      intercalated between layers of hepatocytes and ECs, due to the limitation on HSC
      behavior. When only cytoplasmic processes of quiescent HSCs were adjacent to ECs,
      while the HSC bodies remained on the side of the hepatocytes, the ECs changed
      morphologically and were capable of long-term survival. We confirmed that HSCs
      mediated the communication between hepatocytes and ECs in terms of EC
      morphogenesis. This triculture model allows us to investigate the roles of HSCs
      as both facilitators and integrators of cell-cell communication between
      hepatocytes and ECs, and is useful for investigating heterotypic cellular
      communication in vitro.

PMID- 20799908
TI  - Platelet-rich fibrin is a Bioscaffold and reservoir of growth factors for tissue
      regeneration.
AB  - The platelet-rich fibrin (PRF) is known as a rich source of autologous cytokines
      and growth factors and universally used for tissue regeneration in current
      clinical medicine. However, the microstructure of PRF has not been fully
      investigated nor have been studied the key molecules that differ PRF from
      platelet-rich plasma. We fabricated PRF under Choukroun's protocol and produced
      its extract (PRFe) by freezing at -80 degrees C. The conventional histological,
      immunohistological staining, and scanning electron microscopy images showed the
      microstructure of PRF, appearing as two zones, the zone of platelets and the zone
      of fibrin, which resembled a mesh containing blood cells. The PRFe increased
      proliferation, migration, and promoted differentiation of the human alveolar bone
      marrow stem cells (hABMSCs) at 0.5% concentration in vitro. From the results of
      proteome array, matrix metalloproteinase 9 (MMP9) and Serpin E1 were detected
      especially in PRFe but not in concentrated platelet-rich plasma. Simultaneous
      elevation of MMP9, CD44, and transforming growth factor beta-1 receptor was shown
      at 0.5% PRFe treatment to the hABMSC in immunoblot. Mineralization assay showed
      that MMP9 directly regulated mineralization differentiation of hABMSC.
      Transplantation of the fresh PRF into the mouse calvarias enhanced regeneration
      of the critical-sized defect. Our results strongly support the new
      characteristics of PRF as a bioscaffold and reservoir of growth factors for
      tissue regeneration.

PMID- 20799909
TI  - Influence of shear stress in perfusion bioreactor cultures for the development of
      three-dimensional bone tissue constructs: a review.
AB  - Bone tissue engineering aims to generate clinically applicable bone graft
      substitutes in an effort to ease the demands and reduce the potential risks
      associated with traditional autograft and allograft bone replacement procedures.
      Biomechanical stimuli play an important role under physiologically relevant
      conditions in the normal formation, development, and homeostasis of bone tissue-
      predominantly, strain (predicted levels in vivo for humans <2000 MUepsilon)
      caused by physical deformation, and fluid shear stress (0.8-3 Pa), generated by
      interstitial fluid movement through lacunae caused by compression and tension
      under loading. Therefore, in vitro bone tissue cultivation strategies seek to
      incorporate biochemical stimuli in an effort to create more physiologically
      relevant constructs for grafting. This review is focused on collating information
      pertaining to the relationship between fluid shear stress, cellular deformation,
      and osteogenic differentiation, providing further insight into the optimal
      culture conditions for the creation of bone tissue substitutes.

PMID- 20799910
TI  - PAM2 (piston assisted microsyringe): a new rapid prototyping technique for
      biofabrication of cell incorporated scaffolds.
AB  - Rapid prototyping techniques are widely used to fabricate well-defined three
      dimensional structures of tissue homologs. The piston-assisted microsyringe
      (PAM2) is a rapid prototyping technology specifically developed for low-shear
      stress extrusion of viscous hydrogel solutions containing cells. In this article
      the working parameters of the system were established to guarantee the
      realization of spatially controlled hydrogel scaffolds. Moreover the shear
      stresses acting on the cell membrane during extrusion was investigated through a
      computational fluid-dynamic analysis. The computational models show that the
      shear stress on the cells is of the order of 100 Pa during the extrusion process.
      HepG2 cells encapsulated in alginate were then extruded into spatially organized
      hepatic lobule-like architectures and their viability and function were
      evaluated. The results show that the metabolic fingerprint of the cells is
      preserved with respect to controls and the cells are uniformly distributed
      through the gel scaffold.

PMID- 20799911
TI  - Plasma TIMP-1 and CEA in detection of primary colorectal cancer: a prospective,
      population based study of 4509 high-risk individuals.
AB  - OBJECTIVE: The combination of plasma tissue inhibitor of metalloproteinases-1
      (TIMP-1) and carcinoembryonic antigen (CEA) may be valuable biomarkers for early
      detection of colorectal cancer (CRC). A prospective, population based study was
      performed to validate this hypothesis. MATERIAL AND METHODS: Individuals (n =
      4509) referred for large bowel endoscopy due to symptoms of CRC were
      prospectively included. Baseline data and concurrent diseases were recorded. The
      primary endpoint was detection of CRC and findings at examinations were recorded
      using International Classification of Diseases-10 codes. Plasma was obtained
      before endoscopy and TIMP-1 and CEA levels were determined after the inclusion of
      all individuals. RESULTS: Findings were based on sigmoidoscopy in 1766 and
      colonoscopy in 2743 individuals. Colon cancer (CC) was detected in 184 and rectal
      cancer in 110 individuals. Ten individuals with other cancers, 856 with adenomas
      and 1176 with non-neoplastic findings were also detected. The biomarker levels
      were increased in a variety of diseases including CRC compared to individuals
      without any findings at endoscopy. A multivariable analysis demonstrated that
      both markers were significant and independent detectors of CRC. Combining both
      biomarkers, independent contributions from each (TIMP-1, odds ratio (OR) = 1.8
      (95% confidence interval (CI): 1.4-2.2), p < 0.0001; CEA < 5 ng/ml, OR = 1.6, 1.3
      1.9, or >= 5 ng/ml, OR = 2.3, 95% CI: 1.9-2.7 (p < 0.0001)) were obtained.
      Subgroup analysis of individuals examined by colonoscopy with CC as the endpoint
      showed that combining both biomarkers, independent contributions from each (TIMP
      1, OR = 2.5, 95% CI: 1.8-3.4, p < 0.0001; CEA < 5 ng/ml, OR = 1.4, 95% CI: 1.1
      1.8, and CEA >= 5 ng/ml, OR = 2.3, 95% CI: 1.8-3.0 (p < 0.0001)) were obtained.
      CONCLUSIONS: This prospective validation study supports the use of the
      combination of plasma TIMP-1 and CEA protein measurements as a potential aid in
      early detection of CRC and specifically of CC.

PMID- 20799912
TI  - Effect of ionic stress on apoptosis and the expression of TRPM2 in human
      olfactory neuroepithelial-derived progenitors.
AB  - OBJECTIVES: Disturbed ion homeostasis and apoptosis have been implicated in the
      pathophysiology of bipolar disorder (BD). TRPM2, a nonselective cation channel,
      is involved in apoptosis and is possibly linked with BD. In this study, monensin,
      a sodium ionophore, was used to model the increase [Na(+)](in) and [Ca(2+)](in)
      seen in BD patients. METHODS: Human olfactory neuroepithelial-derived progenitors
      (ONP), which possess neuronal markers, were utilized to investigate the effects
      of monensin on apoptosis and the response of TRPM2, and the effects of lithium on
      the cellular response to monensin. Monensin treatment for 6 h activated caspase
      3, -7 and poly(ADP-ribose) polymerase (PARP), inducing apoptosis. RESULTS:
      [Na(+)](in) increased to twice the basal level and reached steady state after 2 h
      of 10(-6) M monensin treatment, while [Ca(2+)](in) rose after 6 h of the
      treatment. Monensin treatment for 24 h decreased expression of the long form of
      TRPM2, and increased expression of the short form. Lithium (1 mM) pretreatment
      reduced the [Na(+)](in) and [Ca(2+)](in) elevation caused by monensin, down
      regulated the levels of caspase-3, -7 and PARP, and reduced expression of TRPM2.
      CONCLUSIONS: Our findings suggest that the elevation of [Na(+)](in) and
      [Ca(2+)](in) induced ONP apoptosis and altered the expression of TRPM2. Lithium
      pretreatment attenuated the apoptosis induced by ionic stress.

PMID- 20799913
TI  - Activation of Notch signaling in cardiomyocytes during post-infarction
      remodeling.
AB  - OBJECTIVE: Notch signaling is crucial for cell-to-cell interaction during
      cardiovascular development and may influence differentiation, proliferation, and
      apoptotic events. We investigated whether Notch signaling is activated during
      myocardial remodeling in heart failure (HF). DESIGN: Myocardial gene expression
      and localization of Notch receptors (Notch1-4) and ligands (Jagged1-2, and Delta
      like (Dll)-1 and 4) were investigated in rats with HF after induction of
      myocardial infarction and in humans with HF. RESULTS: All Notch receptors and
      ligands investigated and Notch intracellular domain (NICD) were present in rat
      and human myocardial tissue and in cardiomyocytes with differences in their
      relative expression levels and altered expression levels in failing vs. non
      failing myocardium. In isolated rat cardiomyocytes, Notch3 and Notch4 appeared to
      be the major Notch receptors, and Notch3 and Notch4 mRNA levels and NICD-3 and -4
      in cardiomyocytes were upregulated in chronic HF (p < 0.05), indicating increased
      Notch3 and Notch4 signaling. CONCLUSION: The Notch signaling system is present in
      the cardiomyocytes and activated in HF, indicating a role of Notch signaling
      during myocardial remodeling in HF.

PMID- 20799914
TI  - Pediatric weight management programs in Canada: where, what and how?
AB  - Our purpose was to conduct a national environmental scan of pediatric weight
      management programs in Canada. Data were entered by program representatives
      regarding the history, structure, and function of their weight management
      programs using an online survey that our team developed in partnership with the
      Canadian Obesity Network ( www.obesitynetwork.ca ). Of the 18 programs that were
      identified, all included multidisciplinary teams that take a family-centred,
      lifestyle/behavioural therapeutic approach; health services were accessed
      primarily through physician referral. Most programs were launched in the past
      five years with public funding and enrolled ~125 clients/year into one-on-one
      and/or group-based weight management care. Although many participated in research
      and were affiliated with academic institutions, most did not systematically
      evaluate their obesity-related programming. Based on these observations,
      recommendations related to program evaluation, health services delivery, and
      network collaborations are provided to inform future directions for research and
      clinical care that have both domestic and international relevance.

PMID- 20799915
TI  - Fatal thrombotic microangiopathy after a single dose of gemcitabine as fourth
      line palliative treatment for metastasized ductal breast carcinoma.

PMID- 20799916
TI  - Advanced aggressive fibromatosis: Effective palliation with chemotherapy.
AB  - BACKGROUND: Aggressive fibromatosis (AF) is a locally invasive proliferative
      disease. The mainstay of treatment is surgery. Chemotherapy may be considered in
      inoperable AF following failure of hormonal therapy and/or NSAIDs. MATERIAL AND
      METHODS: We conducted a retrospective search of the prospectively maintained
      Royal Marsden Hospital Sarcoma Unit database to identify patients with AF treated
      with chemotherapy between 1987 and 2009. RESULTS: Thirty-nine patients, thirty
      one females and eight males, received one or more lines of chemotherapy. The most
      frequently employed chemotherapy regimens were methotrexate/vinblastine [MTX/VBL]
      (18) and pegylated liposomal doxorubicin [PLD] (14). MTX/VBL was administered
      weekly or every two weeks at MTX 50 mg and VBL 10 mg. Treatment duration ranged
      from three weeks to one year with a median of 4.5 months. Partial response (PR)
      was observed in 11% of cases, disease stabilisation (SD) in 60% and progressive
      disease (PD) in 22%. Time to progression ranged from one month to sixteen years.
      The main toxicities reported were mucositis (4), peripheral neuropathy (3),
      vomiting (3), and neutropenia (3). PLD was administered at 40-50 mg/m(2) every
      four weeks, for up to six cycles. PR was achieved in 33% and in the remainder the
      disease was stable with no progression during treatment. Three (25%) patients
      have so far progressed after treatment. Symptomatic benefit, especially pain
      relief, was reported in 86% (12/14) of cases. Main toxicities included palmar
      plantar erythema (5) and mucositis (4). DISCUSSION: MTX/VBL remains a useful
      combination but PLD is emerging as a well tolerated and effective systemic
      therapy in advanced AF.

PMID- 20799917
TI  - Unilateral renal agenesis and female genital tract pathologies.
AB  - OBJECTIVES: To analyze the gynecological pathologies and extragenital anomalies
      associated with unilateral renal agenesis (URA) and the possible origin of these
      congenital anomalies. DESIGN: Retrospective case-control study. SETTING:
      University Hospital. POPULATION: This study included 276 women with genitourinary
      malformations who had undergone hysterosalpingography (and/or laparoscopy) and
      pyelography with images available for review. METHODS: There were 60 cases of
      women diagnosed with genital malformations and congenital URA and 216 control
      cases of women with genital tract malformations and both kidneys present. All
      cases were categorized according to an embryological-clinical classification and
      the type of Mullerian malformation (American Society for Reproductive Medicine
      (ASRM) classification) and then compared by type for the presence of
      gynecological and extragenital pathologies. MAIN OUTCOME MEASURES: Genital
      malformations, endometriosis, leiomyomas and skeletal anomalies. RESULTS: URA was
      generally associated with either agenesis of all of the derivatives of the
      urogenital ridge on the same side of the body, which were usually found on the
      left, or distal mesonephric anomalies such as a double uterus with a blind
      hemivagina or unilateral cervico-vaginal atresia, which were most frequently on
      the right. The uterine malformations that were most commonly seen in women with
      renal agenesis were bicornis-bicollis, didelphys and unicornuate uteri. Women
      with bicornuate or didelphys uteri and renal agenesis had more gynecological
      pathologies, such as endometriosis, than those with both kidneys present.
      CONCLUSIONS: URA and major uterine malformations are frequently related, and
      individuals with bicornuate or didelphys uteri have endometriosis more often than
      those without renal agenesis. Those malformations that seem to be caused by the
      absence or anomaly of a mesonephric duct lead to renal agenesis, ipsilateral
      vaginal anomalies (blind or atretic hemivagina) and failure of the induction
      function of the Wolffian ducts on the Mullerian ducts, causing uterine
      malformations.

PMID- 20799918
TI  - Predicting cardiotoxicity propensity of the novel iodinated contrast medium GE
      145: Ventricular fibrillation during left coronary arteriography in pigs.
AB  - BACKGROUND: Severe side effects caused by iodinated radiographic contrast media
      (CM) are rare, but can occur in high risk patients and during percutaneous
      coronary intervention. To minimize this risk a new nonionic CM with low inherent
      osmolality has been designed, giving room for a relatively high concentration of
      favorable electrolytes in the isotonic formulation. PURPOSE: To test a new
      radiographic CM (GE-145) in a pig model of cardiotoxicity by comparing its
      ventricular fibrillation (VF) propensity and hemodynamic effects to that of
      iodixanol. MATERIAL AND METHODS: Test agents were injected into the left anterior
      descending coronary artery (LAD) of pigs through an inflated balloon catheter
      (injection volume 25 ml, injection rate 0.4 ml/s, maximum injection time 62.5 s).
      Series 1: GE-145 (338 mg I/ml) + 45 mM NaCl and iodixanol (321 mg I/ml) + 19 mM
      NaCl were injected in five pigs. Series 2: GE-145 (320 mg I/ml) + 45 mM NaCl +
      0.1, 0.3, or 0.7 mM CaCl2 and iodixanol (320 mg I/ml) + 19 mM NaCl + 0.3 mM CaC2
      (Visipaque) were injected in six pigs. RESULTS: Iodixanol + NaCl caused VF in 6
      of 13 injections (46%) after 60.3+/-7.5 s (mean +/- SD). GE-145 + NaCl did not
      cause any VF in 13 injections (0%) (P<0.05). Iodixanol + 19 mM NaCl + 0.3 mM
      CaCl2 caused VF in 9 of 9 injections (100%) after 61+/-4 s. GE-145 + 45 mM NaCl +
      0.1, 0.3, or 0.7 mM CaCl2 did not cause any VF during or after 9 injections of
      each agent (0%) (P<0.05). The least hemodynamic effects were seen with GE-145 +
      45 mM NaCl + 0.7 mM CaCl2. CONCLUSION: In this model of direct administration of
      CM into the LAD of anesthetized pigs, the tested GE-145 formulations had a
      significantly lower propensity to induce VF than iodixanol with electrolytes.
      Favorable hemodynamic properties of GE-145 can be achieved by optimizing
      concentrations of sodium and calcium.

PMID- 20799919
TI  - The frequency of diagnostic errors in radiologic reports depends on the patient's
      age.
AB  - BACKGROUND: Patients who undergo treatment may suffer preventable medical errors.
      Some of these errors are due to diagnostic imaging procedures. PURPOSE: To
      compare the frequency of diagnostic errors in different age groups in an urban
      European population. MATERIAL AND METHODS: A total of 19 129 reported radiologic
      examinations were included. During a 6-month period, the analyzed age groups
      were: children (aged 0-9 years), adults (40-49 years), and elderly (86-95 years).
      RESULTS: The frequency of radiologic examinations per year was 0.3 in children,
      0.6 in adults, and 1.1 in elderly. Significant errors were significantly more
      frequent in the elderly (1.7%) and children (1.4%) compared with adults (0.8%).
      There were 60 false-positive reports and 232 false-negative reports. Most errors
      were made by staff radiologists after hours when they reported on examinations
      outside their area of expertise. CONCLUSION: Diagnostic errors are more frequent
      in children and the elderly compared with middle-aged adults.

PMID- 20799920
TI  - Increased transcutaneous oxygen pressure is an indicator of revascularization
      after peripheral transluminal angioplasty.
AB  - BACKGROUND: In recent years, the use of peripheral transluminal angioplasty (PTA)
      procedures for revascularization of an ischemic limb has increased. Evaluation of
      reperfusion has been carried out by Doppler scan; however, a successful PTA does
      not necessarily result in improved oxygen delivery to the distal parts of the
      limb. PURPOSE: To evaluate the efficacy of the revascularization in diabetic
      patients with critical limb ischemia after treatment with PTA by comparing
      transcutaneous oxygen tension (TcpO2) with the ankle-brachial index (ABI) post
      PTA. MATERIAL AND METHODS: This prospective study included 151 consecutive
      diabetic patients. We evaluated the posterior tibial and dorsalis pedis Doppler,
      ABI, TcpO2, and duplex scan results. If two of these four examinations were
      abnormal, arteriography was carried out and PTA was performed concomitantly. At
      least 64 patients were considered suitable candidates for PTA. RESULTS: The ABI
      increased from 0.67+/-0.25 to 0.84+/-0.25 following PTA (P<0.001). TcpO2
      increased from 27.20+/-11.10 mm Hg to 40+/-12.10 mm Hg after PTA (P<0.001). While
      the TcpO2 could be measured in all patients, the ABI was not measurable in 25.37%
      pretreatment and in 17.91% post treatment. Statistical analysis revealed a scant
      correlation between the techniques used: TcpO2 and ABI (P=0.20). CONCLUSION: Our
      study confirms that the increase in TcpO2 in diabetic patients following PTA
      points to the physiologic significance of microvascular revascularization
      achieved in the treated limb and serves to assess functional improvement in
      tissue oxygenation obtained by PTA. The use of TcpO2 may represent an alternative
      to traditional assessment of peripheral transluminal angioplasty results.

PMID- 20799921
TI  - Phase-contrast X-ray imaging of breast.
AB  - When an X-ray wave traverses an object, its amplitude and phase change, resulting
      in attenuation, interference, and refraction, and in phase-contrast X-ray imaging
      (PCI) these are converted to intensity changes. The relative change of the X-ray
      phase per unit path length is even orders of magnitude larger than that of the X
      ray amplitude, so that the image contrast based on variation of the X-ray phase
      is potentially much stronger than the contrast based on X-ray amplitude
      (absorption contrast). An important medical application of PCI methods is soft
      tissue imaging, where the absorption contrast is inherently weak. It is shown by
      in vitro examples that signs of malignant human breast tumor are enhanced in PCI
      images. Owing to the strong contrast, the radiation dose can be greatly reduced,
      so that a high-resolution phase-contrast X-ray tomography of the breast is
      possible with about 1 mGy mean glandular dose. Scattered radiation carries
      essential information on the atomic and molecular structure of the object, and
      particularly small-angle X-ray scattering can be used to trace cancer. The
      imaging methods developed at the synchrotron radiation facilities will become
      available in the clinical environment with the ongoing development of compact
      radiation sources, which produce intense X-ray beams of sufficient coherence.
      Several developments that are under way are described here.

PMID- 20799922
TI  - Using lidocaine as an additional topical local anesthetic agent in gynecological
      procedures.

PMID- 20799923
TI  - Inclusion of women and gender-specific analyses in randomized clinical trials of
      treatments for depression.
AB  - BACKGROUND: The higher prevalence and cost of depression for women compared with
      men and the possible gender differences in treatment response demand the
      inclusion of women in clinical trials of depression treatments. The 1993 National
      Institutes of Health (NIH) Revitalization Act set a new standard, requiring
      investigators to consider the inclusion of women and analyze outcomes by gender,
      yet compliance with these standards in depression research has not been examined
      systematically. The purpose of this study is to examine the inclusion of women
      and gender-specific analyses in recent randomized clinical trials (RCTs) for
      depression. METHODS: RCTs were identified through a MEDLINE search for trials
      published between January 1 and December 31, 2007, and a Clinicaltrials.gov
      search of self-identified interventional studies to treat depression. RESULTS: Of
      the 150 RCTs for depression published in 2007, 15% did not report the gender
      composition of their sample, 50% of studies did not analyze outcomes by gender,
      and 12% controlled for gender but did not analyze for gender differences. Of the
      768 trials reviewed on Clinicaltrials.gov, 89% reported recruiting male and
      female participants, yet <1% reported an intention to analyze results by gender.
      CONCLUSIONS: Many recent studies of depression treatments include women but do
      not examine outcomes by gender. Understanding how women differ from men in
      response to treatment is critical for enhancing treatment efficacy for the
      greatest number of adults with depression.

PMID- 20799924
TI  - Predictors of breast and cervical cancer screening in a Spanish metropolitan
      area.
AB  - BACKGROUND: Gynecological cancers are an important cause of morbidity and
      mortality. Screening with mammography and Pap smear reduces breast and cervical
      cancer mortality. Neverthless, high participation rates are needed to ensure
      their effectiveness. We sought to assess the use of mammography and Pap smear and
      analyzed predictors of attendance at these cancer screenings in a large
      metropolitan area in Spain. METHODS: We included women surveyed in the Madrid
      City Health Survey 2005. Cancer screening included mammography in the last 2
      years and Pap smear in the last 3 years. Independent variables included
      sociodemographics, chronic diseases, and lifestyles. Predictors of mammography or
      Pap smear attendance were explored using logistic regression. RESULTS: The number
      of women eligible for mammography, aged >or=40 years, was 2580, and the number
      eligible for Pap smear, aged 18-69 years, was 3200. Overall, 60.5% and 76.6%,
      respectively, had received a mammography and Pap smear. Mammography uptake was
      positively associated with age, higher educational level, and osteomuscular
      disease. Obesity and unhealthy lifestyle were associated with nonattendance to
      mammography. Predictors of Pap smear attendance were the same as for mammography.
      CONCLUSIONS: Attendance at gynecological cancer screening in a large metropolitan
      area in Spain is acceptable in the age group for which it is recommended. An
      effort must be made, however, to recruit those women who are less likely to
      undergo screening, as they are at the highest risk of having these diseases.

PMID- 20799925
TI  - Tumor necrosis factor blockade for treatment of inflammatory bowel disease:
      efficacy and safety.
AB  - Inflammatory bowel disease (IBD), including Crohn's Disease (CD) and Ulcerative
      Colitis (UC), is characterized by inflammation of the gastrointestinal tract. In
      UC, inflammation is confined to the mucosa, initially involving the rectum, and
      may extend proximally to involve the entire colon. In CD, transmural inflammation
      may affect any portion of the GI tract. The etiology of these disease processes
      has remained unclear. Therapies are aimed at reducing inflammation and thereby
      improving symptomatology and morbidity. Traditional medical therapies have
      included corticosteroids, aminosalicylates, and immunomodulators. Within the past
      decade, another class of medications has been utilized targeting Tumor Necrosis
      Factor (TNF), a key, early signaling molecule in the inflammatory cascade.
      Increased levels of TNF have been found in the blood, epithelial tissue, and
      stool of patients with active IBD. Anti-TNF medications can not only have direct
      effects on immune system components, but they also can ameliorate apoptotic cell
      death and tight junction compromise in the gastrointestinal epithelium. Several
      randomized, placebo controlled studies have demonstrated the efficacy of these
      medications in achieving induction and maintaining remission of disease. Their
      safety profile, however, remains a concern. There has been a reported association
      of biologic therapy and increased opportunistic infections. A link between
      biologic therapy and the development of certain malignancies has also been
      described. Despite these associations, TNF blockade remains an important
      therapeutic development in the modern therapy of IBD. The role of barrier
      breakdown at the tight junction level in IBD, and of TNF induction of barrier
      disruption, is also discussed.

PMID- 20799927
TI  - The role of vicinal tyrosine residues in the function of Haemophilus influenzae
      ferric-binding protein A.
AB  - The periplasmic FbpA (ferric-binding protein A) from Haemophilus influenzae plays
      a critical role in acquiring iron from host transferrin, shuttling iron from the
      outer-membrane receptor complex to the inner-membrane transport complex
      responsible for transporting iron into the cytoplasm. In the present study, we
      report on the properties of a series of site-directed mutants of two adjacent
      tyrosine residues involved in iron co-ordination, and demonstrate that, in
      contrast with mutation of equivalent residues in the N-lobe of human transferrin,
      the mutant FbpAs retain significant iron-binding affinity regardless of the
      nature of the replacement amino acid. The Y195A and Y196A FbpAs are not only
      capable of binding iron, but are proficient in mediating periplasm-to-cytoplasm
      iron transport in a reconstituted FbpABC pathway in a specialized Escherichia
      coli reporter strain. This indicates that their inability to mediate iron
      acquisition from transferrin is due to their inability to compete for iron with
      receptor-bound transferrin. Wild-type iron-loaded FbpA could be crystalized in a
      closed or open state depending upon the crystallization conditions. The
      synergistic phosphate anion was not present in the iron-loaded open form,
      suggesting that initial anchoring of iron was mediated by the adjacent tyrosine
      residues and that alternate pathways for iron and anion binding and release may
      be considered. Collectively, these results demonstrate that the presence of a
      twin-tyrosine motif common to many periplasmic iron-binding proteins is critical
      for initially capturing the ferric ion released by the outer-membrane receptor
      complex.

PMID- 20799926
TI  - Lysophosphatidylcholines activate G2A inducing G(alphai)-1-/G(alphaq/)11- Ca2(+)
      flux, G(betagamma)-Hck activation and clathrin/beta-arrestin-1/GRK6 recruitment
      in PMNs.
AB  - Lyso-PCs (lysophosphatidylcholines) are a mixture of lipids that accumulate
      during storage of cellular blood components, have been implicated in TRALI
      (transfusion-related acute lung injury) and directly affect the physiology of
      neutrophils [PMNs (polymorphonuclear leucocytes)]. Because the G2A receptor,
      expressed on PMNs, has been reported to recognize lyso-PCs, we hypothesize that
      lyso-PC activation of G2A causes the increases in cytosolic Ca2(+) via release of
      G(alpha) and G(betagamma) subunits, kinase activation, and the recruitment of
      clathrin, beta-arrestin-1 and GRK6 (G-protein receptor kinase 6) to G2A for
      signal transduction. PMNs were isolated by standard techniques, primed with lyso
      PCs for 5-180 s, and lysed for Western blot analysis, immunoprecipitation or
      subcellular fractionation, or fixed and smeared on to slides for digital
      microscopy. The results demonstrated that lyso-PCs cause rapid activation of the
      G2A receptor through S-phosphorylation and internalization resulting in G(alphai)
      1 and G(alphaq/)11 release leading to increases in cytosolic Ca2(+), which was
      inhibited by an antibody to G2A or intracellular neutralization of these
      subunits. Lyso-PCs also caused the release of the G(betagamma) subunit which
      demonstrated a physical interaction (FRET+) with activated Hck (haemopoietic cell
      kinase; Tyr411). Moreover, G2A recruited clathrin, beta-arrestin-1 and GRK6:
      clathrin is important for signal transduction, GRK6 for receptor de
      sensitization, and beta-arrestin-1 both propagates and terminates signals. We
      conclude that lyso-PC activation of G2A caused release of G(alphai)-1,
      G(alphaq/)11 and G(betagamma), resulting in cytosolic Ca2(+) flux, Hck
      activation, and recruitment of clathrin, beta-arrestin-1 and GRK6.

PMID- 20799928
TI  - Only females in poor condition display a clear preference and prefer males with
      an average badge.
AB  - BACKGROUND: Female condition-dependent variation in mate preference may have
      important evolutionary implications, not only within the same population but also
      among populations. There are few experiments, however, on how condition and/or
      genotype influences female mate preferences. The black throat patch of the male
      house sparrow, Passer domesticus, is an intensively studied plumage trait. It is
      often referred to as a 'badge of status' and seems to be involved in female mate
      choice, but differences exist among populations. Between-population variation in
      mate preference may occur for condition-dependent mate preferences. We tested the
      hypothesis that female preference may vary with female quality (body condition).
      Therefore, we measured female preference for badge size using an aviary two
      choice test in which females were presented with two males that had different
      sizes of badges (enlarged or averaged). RESULTS: Overall we did not find a female
      preference for enlarged or average badges, but low-quality females spent more
      time near average badge males. Conversely, high-quality females did not show a
      clear preference. CONCLUSIONS: Collectively, these results indicate that female
      preference varies with female quality. Differences in female condition are causes
      of within-population variation in mating preferences. To our knowledge, our
      results provide one of the first experimental evidences that variation in
      preference for a male ornament is associated with female condition. In our study,
      however, only females of low condition displayed a clear mate preference.
      Differences observed among populations could be partly explained by differences
      in female condition.

PMID- 20799929
TI  - A prospective cohort study of biomarkers of prenatal tobacco smoke exposure: the
      correlation between serum and meconium and their association with infant birth
      weight.
AB  - BACKGROUND: The evaluation of infant meconium as a cumulative matrix of prenatal
      toxicant exposure requires comparison to established biomarkers of prenatal
      exposure. METHODS: We calculated the frequency of detection and concentration of
      tobacco smoke metabolites measured in meconium (nicotine, cotinine, and trans-3'
      hydroxycotinine concentrations) and three serial serum cotinine concentrations
      taken during the latter two-thirds of pregnancy among 337 mother-infant dyads. We
      estimated the duration and intensity of prenatal tobacco smoke exposure using
      serial serum cotinine concentrations and calculated geometric mean meconium
      tobacco smoke metabolite concentrations according to prenatal exposure. We also
      compared the estimated associations between these prenatal biomarkers and infant
      birth weight using linear regression. RESULTS: We detected nicotine (80%),
      cotinine (69%), and trans-3'-hydroxycotinine (57%) in most meconium samples.
      Meconium tobacco smoke metabolite concentrations were positively associated with
      serum cotinine concentrations and increased with the number of serum cotinine
      measurements consistent with secondhand or active tobacco smoke exposure. Like
      serum cotinine, meconium tobacco smoke metabolites were inversely associated with
      birth weight. CONCLUSIONS: Meconium is a useful biological matrix for measuring
      prenatal tobacco smoke exposure and could be used in epidemiological studies that
      enroll women and infants at birth. Meconium holds promise as a biological matrix
      for measuring the intensity and duration of environmental toxicant exposure and
      future studies should validate the utility of meconium using other environmental
      toxicants.

PMID- 20799930
TI  - The MATISSE study: a randomised trial of group art therapy for people with
      schizophrenia.
AB  - BACKGROUND: Art Therapy has been promoted as a means of helping people who may
      find it difficult to express themselves verbally engage in psychological
      treatment. Group Art Therapy has been widely used as an adjunctive treatment for
      people with schizophrenia but there have been few attempts to examine its effects
      and cost effectiveness has not been examined. The MATISSE study aims to evaluate
      the clinical and cost effectiveness of group Art Therapy for people with
      schizophrenia. METHOD/DESIGN: The MATISSE study is a three-arm, parallel group,
      pragmatic, randomised, controlled trial of referral to group Art Therapy plus
      standard care, referral to an attention control 'activity' group plus standard
      care, or standard care alone. Study participants were recruited from inpatient
      and community-based mental health and social care services at four centres in
      England and Northern Ireland. Participants were aged over 18 years with a
      clinical diagnosis of schizophrenia, confirmed by an examination of case notes
      using operationalised criteria. Participants were then randomised via an
      independent and remote telephone randomisation service using permuted stacked
      blocks, stratified by site. Art Therapy and activity groups were made available
      to participants once a week for up to 12 months. Outcome measures were assessed
      by researchers masked to allocation status at 12 and 24 months after
      randomisation. Participants and care givers were aware which arm of the trial
      participants were allocated to. The primary outcomes for the study are global
      functioning (measured using the Global Assessment of Functioning scale) and
      mental health symptoms (measured using the Positive and Negative Syndrome Scale)
      assessed at 24 months. Secondary outcomes were assessed at 12 and 24 months and
      comprise levels of group attendance, social function, satisfaction with care,
      mental wellbeing, and costs. DISCUSSION: We believe that this is the first large
      scale pragmatic trial of Art Therapy for people with schizophrenia. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN46150447.

PMID- 20799931
TI  - Anti-hepatitis B core antigen testing with detection and characterization of
      occult hepatitis B virus by an in-house nucleic acid testing among blood donors
      in Behrampur, Ganjam, Orissa in southeastern India: implications for transfusion.
AB  - BACKGROUND: Occult hepatitis B virus (HBV) infection might transmit viremic units
      into the public blood supply if only hepatitis B surface antigen (HBsAg) testing
      is used for donor screening. Our aim was to evaluate the prevalence of occult HBV
      infection among the HBsAg negative/antiHBc positive donations from a highly HIV
      prevalent region of India. METHODS: A total of 729 HBsAg negative donor units
      were included in this study. Surface gene and precore region were amplified by in
      house nucleic acid test (NAT) for detection of occult HBV infection and surface
      gene was analyzed after direct sequencing. RESULTS: A total of 220 (30.1%) HBsAg
      negative donors were antiHBc positive, of them 66 (30%) were HBV DNA positive by
      NAT. HBV DNA positivity among 164 antiHBc only group, was 27.1% and among 40
      antiHBs positive group was 30.0%. HBV/D (93.3%) was predominant and prevalence of
      both HBV/C and HBV/A was 3.3%. Single or multiple amino acids substitutions were
      found in 95% samples. CONCLUSION: Thus, a considerable number of HBV infected
      donors remain undiagnosed, if only HBsAg is used for screening. Addition of
      antiHBc testing for donor screening, although will lead to rejection of a large
      number of donor units, will definitely eliminate HBV infected donations and help
      in reducing HBV transmission with its potential consequences, especially among
      the immunocompromised population. The HBV genetic diversity found in this donor
      population are in accordance with other parts of India.

PMID- 20799932
TI  - Genomic acquisition of a capsular polysaccharide virulence cluster by non
      pathogenic Burkholderia isolates.
AB  - BACKGROUND: Burkholderia thailandensis is a non-pathogenic environmental
      saprophyte closely related to Burkholderia pseudomallei, the causative agent of
      the often fatal animal and human disease melioidosis. To study B. thailandensis
      genomic variation, we profiled 50 isolates using a pan-genome microarray
      comprising genomic elements from 28 Burkholderia strains and species. RESULTS: Of
      39 genomic regions variably present across the B. thailandensis strains, 13
      regions corresponded to known genomic islands, while 26 regions were novel.
      Variant B. thailandensis isolates exhibited isolated acquisition of a capsular
      polysaccharide biosynthesis gene cluster (B. pseudomallei-like capsular
      polysaccharide) closely resembling a similar cluster in B. pseudomallei that is
      essential for virulence in mammals; presence of this cluster was confirmed by
      whole genome sequencing of a representative variant strain (B. thailandensis
      E555). Both whole-genome microarray and multi-locus sequence typing analysis
      revealed that the variant strains formed part of a phylogenetic subgroup distinct
      from the ancestral B. thailandensis population and were associated with atypical
      isolation sources when compared to the majority of previously described B.
      thailandensis strains. In functional assays, B. thailandensis E555 exhibited
      several B. pseudomallei-like phenotypes, including colony wrinkling, resistance
      to human complement binding, and intracellular macrophage survival. However, in
      murine infection assays, B. thailandensis E555 did not exhibit enhanced virulence
      relative to other B. thailandensis strains, suggesting that additional factors
      are required to successfully colonize and infect mammals. CONCLUSIONS: The
      discovery of such novel variant strains demonstrates how unbiased genomic surveys
      of non-pathogenic isolates can reveal insights into the development and emergence
      of new pathogenic species.

PMID- 20799933
TI  - High mobility group box 1 potentiates the pro-inflammatory effects of interleukin
      1beta in osteoarthritic synoviocytes.
AB  - INTRODUCTION: High mobility group box 1 (HMGB1) is released by necrotic cells or
      secreted in response to inflammatory stimuli. Extracellular HMGB1 may act as a
      pro-inflammatory cytokine in rheumatoid arthritis. We have recently reported that
      HMGB1 is released by osteoarthritic synoviocytes after activation with
      interleukin-1beta (IL-1beta) The present study investigated the role of HMGB1 in
      synovial inflammation in osteoarthritis (OA). METHODS: HMGB1 was determined in
      human synovium using immunohistochemistry, comparing normal to OA. OA
      synoviocytes were incubated with HMGB1 at 15 or 25 ng/ml in the absence or
      presence of IL-1beta (10 ng/ml). Gene expression was analyzed by quantitative PCR
      and protein expression by Western Blot and ELISA. Matrix metalloproteinase (MMP)
      activity was studied by fluorometric procedures and nuclear factor (NF)-kappaB
      activation by transient transfection with a NF-kappaB-luciferase plasmid.
      RESULTS: In the normal synovium, HMGB1 was found in the synovial lining cells,
      sublining cells, and in the vascular wall cells. The distribution of HMGB1 in OA
      synovium was similar but the number of HMGB1 positive cells was higher and HMGB1
      was also present in infiltrated cells. In normal synovial membrane cells, HMGB1
      was found mostly in the nuclei, whereas in OA, HMGB1 was generally found mostly
      in the cytoplasm. In OA synoviocytes, HMGB1 alone at concentrations of 15 or 25
      ng/ml did not affect the production of IL-6, IL-8, CCL2, CCL20, MMP-1 or MMP-3,
      but in the presence of IL-1beta, a significant potentiation of protein and mRNA
      expression, as well as MMP activity was observed. HMGB1 also enhanced the
      phosphorylated ERK1/2 and p38 levels, with a lower effect on phosphorylated Akt.
      In contrast, JNK1/2 phosphorylation was not affected. In addition, HMGB1 at 25
      ng/ml significantly potentiated NF-kappaB activation in the presence of IL-1beta.
      CONCLUSIONS: Our results indicate that HMGB1 is overexpressed in OA synovium and
      mostly present in extracellular form. In OA synoviocytes, HMGB1 cooperates with
      IL-1beta to amplify the inflammatory response leading to the production of a
      number of cytokines, chemokines and MMPs. Our data support a pro-inflammatory
      role for this protein contributing to synovitis and articular destruction in OA.

PMID- 20799934
TI  - Hospitalized adult patients with 2009 influenza A(H1N1) in Beijing, China: risk
      factors for hospital mortality.
AB  - BACKGROUND: In April 2009, the pandemic influenza A(H1N1) virus emerged and
      spread globally. The objective of this study was to describe the independent risk
      factors for hospital mortality and the treatment effect of corticosteroids among
      patients with 2009 influenza A(H1N1) infection. METHODS: We retrospectively
      obtained clinical data of 155 adult patients with confirmed infection of 2009
      influenza A(H1N1) in 23 hospitals in Beijing, China from October 1 to December
      23, 2009. Risk factors for hospital mortality were identified with multivariate
      logistic regression analysis. RESULTS: Among the 155 patients, 90 (58.1%) were
      male, and mean age was 43.0 +/- 18.6 years, and comorbidities were present in 81
      (52.3%) patients. The most common organ dysfunctions included acute respiratory
      failure, altered mental status, septic shock, and acute renal failure.
      Oseltamivir was initiated in 125 patients (80.6%), only 16 patients received
      antiviral therapy within 48 hours after symptom onset. Fifty-two patients (33.5%)
      were treated with systemic corticosteroids, with a median daily dose of 80 mg.
      Twenty-seven patients (17.4%) died during hospital stay. Diabetes [odds ratio
      (OR) 8.830, 95% confidence interval [CI] 2.041 to 38.201, p = 0.004) and lactate
      dehydrogenase (LDH) level (OR 1.240, 95% CI 1.025 to 1.500, p = 0.027) were
      independent risk factors of hospital death, as were septic shock and altered
      mental status. Corticosteroids use was associated with a trend toward higher
      hospital mortality (OR 3.668, 95% CI 0.987 to 13.640, p = 0.052). CONCLUSIONS:
      Hospitalized patients with 2009 H1N1 influenza had relative poor outcome. The
      risk factors at hospitalization may help clinicians to identify the high-risk
      patients. In addition, corticosteroids use should not be regarded as routine
      pharmacologic therapy.

PMID- 20799935
TI  - A case-series study to explore the efficacy of foot orthoses in treating first
      metatarsophalangeal joint pain.
AB  - BACKGROUND: First metatarsophalangeal (MTP) joint pain is a common foot complaint
      which is often considered to be a consequence of altered mechanics. Foot orthoses
      are often prescribed to reduce 1st MTP joint pain with the aim of altering
      dorsiflexion at propulsion. This study explores changes in 1st MTP joint pain and
      kinematics following the use of foot orthoses. METHODS: The effect of modified,
      pre-fabricated foot orthoses (X-line(r)) were evaluated in thirty-two patients
      with 1st MTP joint pain of mechanical origin. The primary outcome was pain
      measured at baseline and 24 weeks using the pain subscale of the foot function
      index (FFI). In a small sub-group of patients (n = 9), the relationship between
      pain and kinematic variables was explored with and without their orthoses, using
      an electromagnetic motion tracking (EMT) system. RESULTS: A significant reduction
      in pain was observed between baseline (median = 48 mm) and the 24 week endpoint
      (median = 14.50 mm, z = -4.88, p < 0.001). In the sub-group analysis, we found no
      relationship between pain reduction and 1st MTP joint motion, and no significant
      differences were found between the 1st MTP joint maximum dorsiflexion or
      ankle/subtalar complex maximum eversion, with and without the orthoses.
      CONCLUSIONS: This observational study demonstrated a significant decrease in 1st
      MTP joint pain associated with the use of foot orthoses. Change in pain was not
      shown to be associated with 1st MTP joint dorsiflexion nor with altered
      ankle/subtalar complex eversion. Further research into the effect of foot
      orthoses on foot function is indicated.

PMID- 20799936
TI  - The essential oil of Brazilian pepper, Schinus terebinthifolia Raddi in larval
      control of Stegomyia aegypti (Linnaeus, 1762).
AB  - BACKGROUND: The ability of mosquitoes of the genus Aedes and its allies, such as
      Stegomyia, to transmit diseases such as dengue and yellow fever, makes them
      important in public health. This study aims to evaluate the use of the essential
      oil of Brazilian pepper in biological control of by assessing and quantifying the
      larvicidal effect against S. aegypti, the only available access to dengue
      control, and test its risk of genotoxicity with Salmonella typhimurium as an
      indicator of safety for its environmental use. RESULTS: The density of the oil
      was 0.8622 g mL-1. Gas chromatography coupled with mass spectrometry revealed six
      major constituents: delta-3-carene (55.43%), alpha-pinene (16.25%), sylvestrene
      (10.67%), germacrene D (2.17), beta-myrcene (1.99%), and isoterpinolene (1.4%).
      The minimum inhibitory dose to larvae development was 862.20 MUg mL-1. The median
      lethal dose (LD50) of the essential oil for larvae was between the concentrations
      of 172.44-344.88 MUg mL-1. There was no mutagenic risk for the essential oil,
      since there were no biochemical or morphological changes in S. typhimurium after
      exposure to the essential oil. CONCLUSIONS: The minimum inhibitory essential oil
      concentration and the median lethal dose pointed to the value of the use of water
      dispersions of Brazilian pepper essential oil as an environmental safe natural
      larvicidal for S. aegypti.

PMID- 20799937
TI  - Anopheline and culicine mosquitoes are not repelled by surfaces treated with the
      entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana.
AB  - BACKGROUND: Entomopathogenic fungi, Metarhizium anisopliae and Beauveria
      bassiana, are promising bio-pesticides for application against adult malaria
      mosquito vectors. An understanding of the behavioural responses of mosquitoes
      towards these fungi is necessary to guide development of fungi beyond the 'proof
      of concept' stage and to design suitable intervention tools. METHODS: Here we
      tested whether oil-formulations of the two fungi could be detected and avoided by
      adult Anopheles gambiae s.s., Anopheles arabiensis and Culex quinquefasciatus.
      The bioassays used a glass chamber divided into three compartments (each 250 *
      250 * 250 mm): release, middle and stimulus compartments. Netting with or without
      fungus was fitted in front of the stimulus compartment. Mosquitoes were released
      and the proportion that entered the stimulus compartment was determined and
      compared between treatments. Treatments were untreated netting (control 1),
      netting with mineral oil (control 2) and fungal conidia formulated in mineral oil
      evaluated at three different dosages (2 * 1010, 4 * 1010 and 8 * 1010 conidia m
      2). RESULTS: Neither fungal strain was repellent as the mean proportion of
      mosquitoes collected in the stimulus compartment did not differ between
      experiments with surfaces treated with and without fungus regardless of the
      fungal isolate and mosquito species tested. CONCLUSION: Our results indicate that
      mineral-oil formulations of M. anisopliae and B. bassiana were not repellent
      against the mosquito species tested. Therefore, both fungi are suitable
      candidates for the further development of tools that aim to control host-seeking
      or resting mosquitoes using entomopathogenic fungi.

PMID- 20799938
TI  - Staying at work with back pain: patients' experiences of work-related help
      received from GPs and other clinicians. A qualitative study.
AB  - BACKGROUND: Low back pain commonly affects work ability, but little is known
      about the work-related help and advice that patients receive from GPs and other
      clinicians. The purpose of this study was to explore the experiences of employed
      people with back pain and their perceptions of how GPs and other clinicians have
      addressed their work difficulties. METHODS: A qualitative approach with thematic
      analysis was used. Individual interviews were carried out with twenty-five
      employed patients who had been referred for back pain rehabilitation. All had
      expressed concern about their ability to work due to low back pain. RESULTS: The
      perception of the participants was that GPs and other clinicians had provided
      little or no work-focused guidance and support and rarely communicated with
      employers. Sickness certification was the main method that GPs used to manage
      participants' work problems. Few had received assistance with temporary
      modifications and many participants had remained in work despite the advice they
      had received. There was little expectation of what GPs and other clinicians could
      offer to address work issues. CONCLUSIONS: These findings question the ability of
      GPs and other clinicians to provide work-focused support and advice to patients
      with low back pain. Future research is recommended to explore how the workplace
      problems of patients can be best addressed by health professionals.

PMID- 20799939
TI  - The relevance of long head biceps degeneration in the presence of rotator cuff
      tears.
AB  - BACKGROUND: Long head biceps (LHB) degeneration in combination with rotator cuff
      tears can be a source of chronic shoulder pain. LHB tenotomy is an approved
      surgical procedure for pain reduction and improvement of joint function, however,
      the pathophysiology of LHB degeneration is not fully understood. In the
      literature, neoangiogenesis in tendon tissue has previously been shown to be
      associated with tendon degeneration. Vascular Endothelial Growth Factor (VEGF) is
      an important inducer of neoangiogenesis. The hypotheses are first that an
      elevated VEGF expression and vessel density can be found in degenerated LHB
      tissue and second that there is a relation between VEGF expression, vessel
      density and the different types of rotator cuff tears. METHODS: LHB samples of
      116 patients with degenerative rotator cuff tears were harvested during
      arthroscopic tenotomy. The samples were dehydrated and paraffin embedded. VEGF
      expression was determined using immunohistochemistry. Vessel density and vessel
      size were determined on Masson-Goldner stained tissue sections. On the basis of
      intraoperative findings, patients were assigned to 4 different groups (control
      group, partial thickness rotator cuff tear, full thickness rotator cuff tear and
      cuff arthropathy). Partial thickness rotator cuff tears were classified according
      to Ellman grade I-III, full thickness rotator cuff tears according to Bateman's
      classification (grade I-IV). The control group consisted of eight healthy tendon
      samples. RESULTS: VEGF expression in the LHB was significantly higher in the
      presence of rotator cuff tears than in healthy tendons (p < 0.05) whereas vessel
      density and vessel size were significantly higher in the LHB of patients with
      cuff arthropathy (p < 0.05). Furthermore, there was significantly higher VEGF
      expression in LHB samples from patients with articular-sided compared to bursal
      sided partial thickness rotator cuff tears (p < 0.05). No significant dependence
      was found between VEGF expression, vessel size and vessel density in LHB of
      patients with full thickness rotator cuff tears and the extent of the cuff tear
      following Bateman's classification. CONCLUSION: Elevated VEGF expression can be
      detected in degenerated LHB tissue. The quantity of VEGF expression and vessels
      are related to the extent of LHB degeneration.

PMID- 20799940
TI  - Investigating portable fluorescent microscopy (CyScope) as an alternative rapid
      diagnostic test for malaria in children and women of child-bearing age.
AB  - BACKGROUND: Prompt and correct diagnosis of malaria is crucial for accurate
      epidemiological assessment and better case management, and while the gold
      standard of light microscopy is often available, it requires both expertise and
      time. Portable fluorescent microscopy using the CyScope offers a potentially
      quicker, easier and more field-applicable alternative. This article reports on
      the strengths, limitations of this methodology and its diagnostic performance in
      cross-sectional surveys on young children and women of child-bearing age.
      METHODS: 552 adults (99% women of child-bearing age) and 980 children (99% <= 5
      years of age) from rural and peri-urban regions of Ugandan were examined for
      malaria using light microscopy (Giemsa-stain), a lateral-flow test (Paracheck-Pf)
      and the CyScope. Results from the surveys were used to calculate diagnostic
      performance (sensitivity and specificity) as well as to perform a receiver
      operating characteristics (ROC) analyses, using light microscopy as the gold
      standard. RESULTS: Fluorescent microscopy (qualitative reads) showed reduced
      specificity (<40%), resulting in higher community prevalence levels than those
      reported by light microscopy, particularly in adults (+180% in adults and +20% in
      children). Diagnostic sensitivity was 92.1% in adults and 86.7% in children, with
      an area under the ROC curve of 0.63. Importantly, optimum performance was
      achieved for higher parasitaemia (>400 parasites/MUL blood): sensitivity of 64.2%
      and specificity of 86.0%. Overall, the diagnostic performance of the CyScope was
      found inferior to that of Paracheck-Pf. DISCUSSION: Fluorescent microscopy using
      the CyScope is certainly a field-applicable and relatively affordable solution
      for malaria diagnoses especially in areas where electrical supplies may be
      lacking. While it is unlikely to miss higher parasitaemia, its application in
      cross-sectional community-based studies leads to many false positives (i.e. small
      fluorescent bodies of presently unknown origin mistaken as malaria parasites).
      Without recourse to other technologies, arbitration of these false positives is
      presently equivocal, which could ultimately lead to over-treatment; something
      that should be further explored in future investigations if the CyScope is to be
      more widely implemented.

PMID- 20799941
TI  - TRAIL death receptor-4, decoy receptor-1 and decoy receptor-2 expression on CD8+
      T cells correlate with the disease severity in patients with rheumatoid
      arthritis.
AB  - BACKGROUND: Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory
      disorder. Although the pathogenesis of disease is unclear, it is well known that
      T cells play a major role in both development and perpetuation of RA through
      activating macrophages and B cells. Since the lack of TNF-Related Apoptosis
      Inducing Ligand (TRAIL) expression resulted in defective thymocyte apoptosis
      leading to an autoimmune disease, we explored evidence for alterations in
      TRAIL/TRAIL receptor expression on peripheral T lymphocytes in the molecular
      mechanism of RA development. METHODS: The expression of TRAIL/TRAIL receptors on
      T cells in 20 RA patients and 12 control individuals were analyzed using flow
      cytometry. The correlation of TRAIL and its receptor expression profile was
      compared with clinical RA parameters (RA activity scored as per DAS28) using
      Spearman Rho Analysis. RESULTS: While no change was detected in the ratio of CD4+
      to CD8+ T cells between controls and RA patient groups, upregulation of TRAIL and
      its receptors (both death and decoy) was detected on both CD4+ and CD8+ T cells
      in RA patients compared to control individuals. Death Receptor-4 (DR4) and the
      decoy receptors DcR1 and DcR2 on CD8+ T cells, but not on CD4+ T cells, were
      positively correlated with patients' DAS scores. CONCLUSIONS: Our data suggest
      that TRAIL/TRAIL receptor expression profiles on T cells might be important in
      revelation of RA pathogenesis.

PMID- 20799942
TI  - Integration of transcript expression, copy number and LOH analysis of
      infiltrating ductal carcinoma of the breast.
AB  - BACKGROUND: A major challenge in the interpretation of genomic profiling data
      generated from breast cancer samples is the identification of driver genes as
      distinct from bystander genes which do not impact tumorigenesis. One way to
      assess the relative importance of alterations in the transcriptome profile is to
      combine parallel analyses that assess changes in the copy number alterations
      (CNAs). This integrated analysis permits the identification of genes with altered
      expression that map within specific chromosomal regions which demonstrate copy
      number alterations, providing a mechanistic approach to identify the 'driver
      genes'. METHODS: We have performed whole genome analysis of CNAs using the
      Affymetrix 250K Mapping array on 22 infiltrating ductal carcinoma samples (IDCs).
      Analysis of transcript expression alterations was performed using the Affymetrix
      U133 Plus2.0 array on 16 IDC samples. Fourteen IDC samples were analyzed using
      both platforms and the data integrated. We also incorporated data from loss of
      heterozygosity (LOH) analysis to identify genes showing altered expression in LOH
      regions. RESULTS: Common chromosome gains and amplifications were identified at
      1q21.3, 6p21.3, 7p11.2-p12.1, 8q21.11 and 8q24.3. A novel amplicon was identified
      at 5p15.33. Frequent losses were found at 1p36.22, 8q23.3, 11p13, 11q23, and
      22q13. Over 130 genes were identified with concurrent increases or decreases in
      expression that mapped to these regions of copy number alterations. LOH analysis
      revealed three tumors with whole chromosome or p arm allelic loss of chromosome
      17. Genes were identified that mapped to copy neutral LOH regions. LOH with
      accompanying copy loss was detected on Xp24 and Xp25 and genes mapping to these
      regions with decreased expression were identified. Gene expression data
      highlighted the PPARalpha/RXRalpha Activation Pathway as down-regulated in the
      tumor samples. CONCLUSION: We have demonstrated the utility of the application of
      integrated analysis using high resolution CGH and whole genome transcript
      analysis for detecting driver genes in IDC. The high resolution platform allowed
      a refined demarcation of CNAs and gene expression profiling provided a mechanism
      to detect genes directly impacted by the CNA. This is the first report of LOH
      integrated with gene expression in IDC using a high resolution platform.

PMID- 20799943
TI  - Molecular epidemiology of a hepatitis C virus epidemic in a haemodialysis unit:
      outbreak investigation and infection outcome.
AB  - BACKGROUND: HCV is a leading cause of liver chronic diseases all over the world.
      In developed countries the highest prevalence of infection is reported among
      intravenous drug users and haemodialysis (HD) patients. The present report is to
      identify the pathway of HCV transmission during an outbreak of HCV infection in a
      privately run haemodialysis (HD) unit in Italy in 2005. METHODS: Dynamics of the
      outbreak and infection clinical outcomes were defined through an ambi-directional
      cohort study. Molecular epidemiology techniques were used to define the
      relationships between the viral variants infecting the patients and confirm the
      outbreak. Risk analysis and auditing procedures were carried out to define the
      transmission pathway(s). RESULTS: Of the 50 patients treated in the HD unit 5
      were already anti-HCV positive and 13 became positive during the study period (AR
      = 28.9%). Phylogenic analysis identified that, all the molecularly characterized
      incident cases (10 out of 13), were infected with the same viral variant of one
      of the prevalent cases. The multivariate analysis and the auditing procedure
      disclosed a single event of multi-dose vials heparin contamination as the cause
      of transmission of the infection in 11 out of the 13 incident cases; 2 additional
      incident cases occurred possibly as a result of inappropriate risk management.
      DISCUSSION: More than 30% of all HCV infections in developed countries results
      from poor application of standard precautions during percutaneous procedures.
      Comprehensive strategy which included: educational programmes, periodical
      auditing on standard precaution, use of single-dose vials whenever possible,
      prospective surveillance for blood-borne infections (including a system of prompt
      notification) and risk assessment/management dedicated staff are the cornerstone
      to contain and prevent outbreaks in HD CONCLUSIONS: The outbreak described should
      serve as a reminder to HD providers that patients undergoing dialysis are at risk
      for HCV infection and that HCV may be easily transmitted whenever standard
      precautions are not strictly applied.

PMID- 20799944
TI  - Genes and pathways for CO2 fixation in the obligate, chemolithoautotrophic
      acidophile, Acidithiobacillus ferrooxidans, carbon fixation in A. ferrooxidans.
AB  - BACKGROUND: Acidithiobacillus ferrooxidans is chemolithoautotrophic gamma
      proteobacterium that thrives at extremely low pH (pH 1-2). Although a substantial
      amount of information is available regarding CO2 uptake and fixation in a variety
      of facultative autotrophs, less is known about the processes in obligate
      autotrophs, especially those living in extremely acidic conditions, prompting the
      present study. RESULTS: Four gene clusters (termed cbb1-4) in the A. ferrooxidans
      genome are predicted to encode enzymes and structural proteins involved in carbon
      assimilation via the Calvin-Benson-Bassham (CBB) cycle including form I of
      ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO, EC 4.1.1.39) and the
      CO2-concentrating carboxysomes. RT-PCR experiments demonstrated that each gene
      cluster is a single transcriptional unit and thus is an operon. Operon cbb1 is
      divergently transcribed from a gene, cbbR, encoding the LysR-type transcriptional
      regulator CbbR that has been shown in many organisms to regulate the expression
      of RubisCO genes. Sigma70-like -10 and -35 promoter boxes and potential CbbR
      binding sites (T-N11-A/TNA-N7TNA) were predicted in the upstream regions of the
      four operons. Electrophoretic mobility shift assays (EMSAs) confirmed that
      purified CbbR is able to bind to the upstream regions of the cbb1, cbb2 and cbb3
      operons, demonstrating that the predicted CbbR-binding sites are functional in
      vitro. However, CbbR failed to bind the upstream region of the cbb4 operon that
      contains cbbP, encoding phosphoribulokinase (EC 2.7.1.19). Thus, other factors
      not present in the assay may be required for binding or the region lacks a
      functional CbbR-binding site. The cbb3 operon contains genes predicted to encode
      anthranilate synthase components I and II, catalyzing the formation of
      anthranilate and pyruvate from chorismate. This suggests a novel regulatory
      connection between CO2 fixation and tryptophan biosynthesis. The presence of a
      form II RubisCO could promote the ability of A. ferrooxidans to fix CO2 at
      different concentrations of CO2. CONCLUSIONS: A. ferrooxidans has features of cbb
      gene organization for CO2-assimilating functions that are characteristic of
      obligate chemolithoautotrophs and distinguish this group from facultative
      autotrophs. The most conspicuous difference is a separate operon for the cbbP
      gene. It is hypothesized that this organization may provide greater flexibility
      in the regulation of expression of genes involved in inorganic carbon
      assimilation.

PMID- 20799945
TI  - Medial pelvic migration of the lag screw in a short gamma nail after hip fracture
      fixation: a case report and review of the literature.
AB  - Hip fractures are a common injury among the elderly. Internal fixation with an
      intramedullary (IM) system has gained popularity for the treatment of
      intertrochanteric femur fractures. Multiple complications associated with IM
      fracture fixation have been described, however, we report a rare complication of
      medial pelvic migration of the lag screw of a short IM nail in a stable construct
      ten weeks post surgery. The patient was subsequently treated with Lag Screw
      removal and revision surgery with a shorter Lag Screw and an accessory cannulated
      screw acting as a de-rotational device. The patient did well with the revision
      surgery and was able to return to full activities.

PMID- 20799946
TI  - Modeling the epidemiological history of plague in Central Asia: palaeoclimatic
      forcing on a disease system over the past millennium.
AB  - BACKGROUND: Human cases of plague (Yersinia pestis) infection originate,
      ultimately, in the bacterium's wildlife host populations. The epidemiological
      dynamics of the wildlife reservoir therefore determine the abundance,
      distribution and evolution of the pathogen, which in turn shape the frequency,
      distribution and virulence of human cases. Earlier studies have shown clear
      evidence of climatic forcing on contemporary plague abundance in rodents and
      humans. RESULTS: We find that high-resolution palaeoclimatic indices correlate
      with plague prevalence and population density in a major plague host species, the
      great gerbil (Rhombomys opimus), over 1949-1995. Climate-driven models trained on
      these data predict independent data on human plague cases in early 20th-century
      Kazakhstan from 1904-1948, suggesting a consistent impact of climate on large
      scale wildlife reservoir dynamics influencing human epidemics. Extending the
      models further back in time, we also find correspondence between their
      predictions and qualitative records of plague epidemics over the past 1500 years.
      CONCLUSIONS: Central Asian climate fluctuations appear to have had significant
      influences on regional human plague frequency in the first part of the 20th
      century, and probably over the past 1500 years. This first attempt at
      ecoepidemiological reconstruction of historical disease activity may shed some
      light on how long-term plague epidemiology interacts with human activity. As
      plague activity in Central Asia seems to have followed climate fluctuations over
      the past centuries, we may expect global warming to have an impact upon future
      plague epidemiology, probably sustaining or increasing plague activity in the
      region, at least in the rodent reservoirs, in the coming decades.See commentary:
      http://www.biomedcentral.com/1741-7007/8/108.

PMID- 20799947
TI  - Hypertonic saline increases lung epithelial lining fluid glutathione and
      thiocyanate: two protective CFTR-dependent thiols against oxidative injury.
AB  - BACKGROUND: Cystic fibrosis is a debilitating lung disease due to mutations in
      the cystic fibrosis transmembrane conductance regulator protein (CFTR) and is
      associated with chronic infections resulting in elevated myeloperoxidase activity
      and generation of hypochlorous acid (HOCl). CFTR mutations lead to decreased
      levels of glutathione (GSH) and thiocyanate (SCN) in the epithelial lining fluid
      (ELF). Hypertonic saline is used to improve lung function however the mechanism
      is uncertain. METHODS: In the present study, the effect of GSH and SCN on HOCl
      mediated cell injury and their changes in the ELF after hypertonic saline
      nebulization in wild type (WT) and CFTR KO mice was examined. CFTR sufficient and
      deficient lung cells were assessed for GSH, SCN and corresponding sensitivity
      towards HOCl-mediated injury, in vitro. RESULTS: CFTR (-) cells had lower
      extracellular levels of both GSH and SCN and were more sensitive to HOCl-mediated
      injury. In vivo, hypertonic saline increased ELF GSH in the WT and to a lesser
      extent in the CFTR KO mice but only SCN in the WT ELF. Finally, potential
      protective effects of GSH and SCN at concentrations found in the ELF against HOCl
      toxicity were examined in vitro. CONCLUSIONS: While the concentrations of GSH and
      SCN associated with the WT ELF protect against HOCl toxicity, those found in the
      CFTR KO mice were less sufficient to inhibit cell injury. These data suggests
      that CFTR has important roles in exporting GSH and SCN which are protective
      against oxidants and that hypertonic saline treatment may have beneficial effects
      by increasing their levels in the lung.

PMID- 20799948
TI  - Stigmatizing attitudes and low levels of knowledge but high willingness to
      participate in HIV management: a community-based survey of pharmacies in Pune,
      India.
AB  - BACKGROUND: The World Health Organization (WHO) recommends that the role of
      pharmacists in low-income settings be expanded to address the increasing
      complexity of HIV antiretroviral (ARV) and co-infection drug regimens. However,
      in many such settings including in India, many pharmacists and pharmacy workers
      are often neither well trained nor aware of the intricacies of HIV treatment. The
      aims of our study were; to determine the availability of ARVs, provision of ARVs,
      knowledge about ARVs, attitudes towards HIV-infected persons and self-perceived
      need for training among community-based pharmacies in an urban area of India.
      METHODS: We performed a survey of randomly selected, community-based pharmacies
      located in Pune, India, in 2004-2005 to determine the availability of ARVs at
      these pharmacies, how they were providing ARVs and their self-perceived need for
      training. We also assessed knowledge, attitudes and perceptions on HIV and ARVs
      and factors associated with stocking ARVs. RESULTS: Of 207 pharmacies included in
      the survey, 200 (96.6%) were single, private establishments. Seventy-three
      (35.3%) pharmacies stocked ARVs and 38 (18.4%) ordered ARVs upon request. The
      reported median number of ARV pills that patients bought at one time was 30, a
      two week supply of ARVs (range: 3-240 pills). Six (2.9%) pharmacy respondents
      reported selling non-allopathic medicines (i.e. Ayurvedic, homeopathy) for HIV.
      Ninety (44.2%) pharmacy respondents knew that ARVs cannot cure HIV, with those
      stocking ARVs being more likely to respond correctly (60.3% vs. 34.8%, p =
      0.001). Respondents of pharmacies which stocked ARVs were also more likely to
      believe it was a professional obligation to provide medications to HIV-infected
      persons (91.8% vs. 78.8%, p = 0.007) but they were also more likely to believe
      that HIV-infected persons are unable to adhere to their medicines (79.5% vs.
      40.9%, p < 0.01). Knowledge of the most common side effects of nevirapine,
      abnormal liver enzyme profile and skin rash, was reported correctly by 8 (3.9%)
      and 23 (11.1%) respondents, respectively. Seven (3.4%) respondents reported that
      they had received special training on HIV, 3 (1.5%) reported receipt of special
      training on ART and 167 (80.7%) reported that they believed that pharmacy staff
      should get special training on ART. CONCLUSION: There is a high willingness to
      participate in HIV management among community-based pharmacies but there is a
      tremendous need for training on HIV therapies. Furthermore, stigmatizing
      attitudes towards HIV-infected persons persist and interventions to reduce stigma
      are needed, particularly among those that stock ARVs.

PMID- 20799949
TI  - The association between ATM D1853N polymorphism and breast cancer susceptibility:
      a meta-analysis.
AB  - BACKGROUND: Emerging evidence suggests that ataxia telangiectasia-mutated (ATM)
      is involved in numerous damage repair signaling pathways and cell-cycle
      checkpoints. Heterozygous carriers of ATM-mutations have an increased risk for
      the development of breast cancer. The purpose of this study is to evaluate the
      association between ATM exon39 5557G > A (D1853N, rs1801516) polymorphism and
      breast cancer susceptibility with the use of a meta-analysis. METHODS: By
      searching PubMed and Embase databases, a total of 9 epidemiological studies with
      4,191 cases and 3,780 controls were identified. Crude odds ratios (ORs) and their
      corresponding 95% confidence intervals (CIs) for ATM D1853N polymorphism and
      breast cancer risk were calculated using fixed- or random-effects model based on
      the degree of heterogeneity among studies. RESULTS: No significant association
      between the ATM D1853N polymorphism and breast cancer risk was observed in
      overall analysis (GA versus GG: OR = 1.18; 95% CI, 0.90-1.53; AA versus GG: OR =
      0.77; 95% CI, 0.58-1.03; dominant model: OR = 1.16; 95% CI, 0.89-1.51; and
      recessive model: OR = 0.78; 95% CI, 0.59-1.04, respectively). CONCLUSION: Our
      results indicate that ATM D1853N polymorphism is not a risk factor for developing
      breast cancer.

PMID- 20799950
TI  - L1CAM expression in endometrial carcinomas is regulated by usage of two different
      promoter regions.
AB  - BACKGROUND: The L1 cell adhesion molecule (L1CAM) was originally identified as a
      neural adhesion molecule involved in axon guidance. In many human epithelial
      carcinomas L1CAM is overexpressed and thereby augments cell motility, invasion
      and metastasis formation. L1CAM positive carcinomas are associated with bad
      prognosis. Recent data point out that L1CAM is regulated in a fashion similar to
      epithelial-mesenchymal transition (EMT). Previous studies have implied the
      transcription factors Slug and/or beta-catenin in L1CAM transcriptional
      regulation. However, the regulation of human L1CAM expression at the
      transcriptional level is not well understood. RESULTS: To better understand the
      molecular basis of L1CAM transcriptional regulation, we carried out a detailed
      characterization of the human L1CAM promoter. We identified two transcription
      start sites, the first in front of a non-translated exon 0 (promoter 1) and the
      other next to the first protein-coding exon 1 (promoter 2). Both sites could be
      verified in endometrial carcinoma (EC) cell lines and appear to be used in a cell
      type specific manner. The two identified promoter regions showed activity in
      luciferase reporter assays. Chromatin-IP analyses confirmed the in silico
      predicted E-boxes, binding sites for transcription factors Snail and Slug, as
      well as Lef-1 sites, which are related to beta-catenin-mediated transcriptional
      regulation, in both promoters. Overexpression of beta-catenin exclusively
      augmented activity of promoter 1 whereas Slug enhanced promoter 1 and 2 activity
      suggesting that both promoters can be active. Overexpression of beta-catenin or
      Slug could upregulate L1CAM expression in a cell-type specific manner.
      CONCLUSIONS: Our results, for the first time, provide evidence that the L1CAM
      gene has two functionally active promoter sites that are used in a cell-type
      specific manner. Slug and beta-catenin are involved L1CAM transcriptional
      regulation. Nevertheless, Slug rather than beta-catenin levels are correlated
      with L1CAM expression in EC cell lines. Our findings suggest that the L1CAM
      transcriptional regulation is more complex than anticipated and this study
      provides the basis for a better understanding of L1CAM regulation in non
      neuronal/tumor cells.

PMID- 20799951
TI  - Leucine-rich repeat protein PRAME: expression, potential functions and clinical
      implications for leukaemia.
AB  - PRAME/MAPE/OIP4 is a germinal tissue-specific gene that is also expressed at high
      levels in haematological malignancies and solid tumours. The physiological
      functions of PRAME in normal and tumour cells are unknown, although a role in the
      regulation of retinoic acid signalling has been proposed. Sequence homology and
      structural predictions suggest that PRAME is related to the leucine-rich repeat
      (LRR) family of proteins, which have diverse functions. Here we review the
      current knowledge of the structure/function of PRAME and its relevance in
      leukaemia.

PMID- 20799952
TI  - Phylogenetic diversification patterns and divergence times in ground beetles
      (Coleoptera: Carabidae: Harpalinae).
AB  - BACKGROUND: Harpalinae is a species rich clade of carabid beetles with many
      unusual morphological forms and ecological interactions. How this diversity
      evolved has been difficult to reconstruct, perhaps because harpalines underwent a
      rapid burst of diversification early in their evolutionary history. Here we
      investigate the tempo of evolution in harpalines using molecular divergence
      dating techniques and explore the rates of lineage accumulation in harpalines and
      their sister group. RESULTS: According to molecular divergence date estimates,
      harpalines originated in the mid Cretaceous but did not diversify extensively
      until the late Cretaceous or early Paleogene about 32 million years after their
      origin. In a relatively small window of time, harpalines underwent rapid
      speciation. Harpalines have a relative high net diversification rate and
      increased cladogenesis in some regions of the clade. We did not see a significant
      decrease in diversification rate through time in the MCCR test, but a model of
      diversification with two shift points to lower diversification rates fit the
      harpaline lineage accumulation through time the best. CONCLUSIONS: Our results
      indicate harpalines are significantly more diverse and have higher
      diversification than their sistergroup. Instead of an immediate burst of
      explosive diversification, harpalines may have had a long "fuse" before major
      lineages diversified during the early Paleogene when other taxa such as mammals,
      birds, and some flowering plants were also rapidly diversifying.

PMID- 20799953
TI  - Mapping haplotype-haplotype interactions with adaptive LASSO.
AB  - BACKGROUND: The genetic etiology of complex diseases in human has been commonly
      viewed as a complex process involving both genetic and environmental factors
      functioning in a complicated manner. Quite often the interactions among genetic
      variants play major roles in determining the susceptibility of an individual to a
      particular disease. Statistical methods for modeling interactions underlying
      complex diseases between single genetic variants (e.g. single nucleotide
      polymorphisms or SNPs) have been extensively studied. Recently, haplotype-based
      analysis has gained its popularity among genetic association studies. When
      multiple sequence or haplotype interactions are involved in determining an
      individual's susceptibility to a disease, it presents daunting challenges in
      statistical modeling and testing of the interaction effects, largely due to the
      complicated higher order epistatic complexity. RESULTS: In this article, we
      propose a new strategy in modeling haplotype-haplotype interactions under the
      penalized logistic regression framework with adaptive L1-penalty. We consider
      interactions of sequence variants between haplotype blocks. The adaptive L1
      penalty allows simultaneous effect estimation and variable selection in a single
      model. We propose a new parameter estimation method which estimates and selects
      parameters by the modified Gauss-Seidel method nested within the EM algorithm.
      Simulation studies show that it has low false positive rate and reasonable power
      in detecting haplotype interactions. The method is applied to test haplotype
      interactions involved in mother and offspring genome in a small for gestational
      age (SGA) neonates data set, and significant interactions between different
      genomes are detected. CONCLUSIONS: As demonstrated by the simulation studies and
      real data analysis, the approach developed provides an efficient tool for the
      modeling and testing of haplotype interactions. The implementation of the method
      in R codes can be freely downloaded from
      http://www.stt.msu.edu/~cui/software.html.

PMID- 20799954
TI  - Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular
      carcinoma invasion.
AB  - BACKGROUND: Micro-ribonucleic acid (miRNA)-199a-5p has been reported to be
      decreased in hepatocellular carcinoma (HCC) compared to normal tissue. Discoidin
      domain receptor-1 (DDR1) tyrosine kinase, involved in cell invasion-related
      signaling pathway, was predicted to be a potential target of miR-199a-5p by the
      use of miRNA target prediction algorithms. The aim of this study was to
      investigate the role of miR-199a-5p and DDR1 in HCC invasion. METHODS: Mature miR
      199a-5p and DDR1 expression were evaluated in tumor and adjacent non-tumor liver
      tissues from 23 patients with HCC undergoing liver resection and five hepatoma
      cell lines by the use of real-time quantitative RT-PCR (qRT-PCR) analysis. The
      effect of aberrant miR-199a-5p expression on cell invasion was assessed in vitro
      using HepG2 and SNU-182 hepatoma cell lines. Luciferase reporter assay was
      employed to validate DDR1 as a putative miR-199a-5p target gene. Regulation of
      DDR1 expression by miR-199a-5p was assessed by the use qRT-PCR and western
      blotting analysis. RESULTS: A significant down-regulation of miR-199a-5p was
      observed in 65.2% of HCC tissues and in four of five cell lines. In contrast,
      DDR1 expression was significantly increased in 52.2% of HCC samples and in two of
      five cell lines. Increased DDR1 expression in HCC was associated with advanced
      tumor stage. DDR1 was shown to be a direct target of miR-199a-5p by luciferase
      reporter assay. Transfection of miR-199a-5p inhibited invasion of HepG2 but not
      SNU-182 hepatoma cells. CONCLUSIONS: Decreased expression of miR-199a-5p
      contributes to increased cell invasion by functional deregulation of DDR1
      activity in HCC. However, the effect of miR-199a-5p on DDR1 varies among
      individuals and hepatoma cell lines. These findings may have significant
      translational relevance for development of new targeted therapies as well as
      prognostic prediction for patients with HCC.

PMID- 20799955
TI  - DNA methylation patterns provide insight into epigenetic regulation in the
      Pacific oyster (Crassostrea gigas).
AB  - BACKGROUND: DNA methylation is an epigenetic mechanism with important regulatory
      functions in animals. While the mechanism itself is evolutionarily ancient, the
      distribution and function of DNA methylation is diverse both within and among
      phylogenetic groups. Although DNA methylation has been well studied in mammals,
      there are limited data on invertebrates, particularly molluscs. Here we
      characterize the distribution and investigate potential functions of DNA
      methylation in the Pacific oyster (Crassostrea gigas). RESULTS: Methylation
      sensitive PCR and bisulfite sequencing PCR approaches were used to identify CpG
      methylation in C. gigas genes and demonstrated that this species possesses
      intragenic methylation. In silico analysis of CpGo/e ratios in publicly available
      sequence data suggests that DNA methylation is a common feature of the C. gigas
      genome, and that specific functional categories of genes have significantly
      different levels of methylation. CONCLUSIONS: The Pacific oyster genome displays
      intragenic DNA methylation and contains genes necessary for DNA methylation in
      animals. Results of this investigation suggest that DNA methylation has
      regulatory functions in Crassostrea gigas, particularly in gene families that
      have inducible expression, including those involved in stress and environmental
      responses.

PMID- 20799956
TI  - The influence of demographic characteristics, living conditions, and trauma
      exposure on the overall health of a conflict-affected population in Southern
      Sudan.
AB  - BACKGROUND: There remains limited evidence on how armed conflict affects overall
      physical and mental well-being rather than specific physical or mental health
      conditions. The aim of this study was to investigate the influence of demographic
      characteristics, living conditions, and violent and traumatic events on general
      physical and mental health in Southern Sudan which is emerging from 20 years of
      armed conflict. METHODS: A cross-sectional survey of 1228 adults was conducted in
      November 2007 in the town of Juba, the capital of Southern Sudan. Multivariate
      linear regression analysis was used to investigate the associations and relative
      influence of variables in three models of demographic characteristics, living
      conditions, and trauma exposure, on general physical and mental health status.
      These models were run separately and also as a combined model. Data quality and
      the internal consistency of the health status instrument (SF-8) were assessed.
      RESULTS: The variables in the multivariate analysis (combined model) with
      negative coefficients of association with general physical health and mental
      health (i.e. worse health), respectively, were being female (coef. -2.47; -2.63),
      higher age (coef.-0.16; -0.17), absence of soap in the household (physical health
      coef. -2.24), and experiencing within the past 12 months a lack of food and/or
      water (coef. -1.46; -2.27) and lack of medical care (coef.-3.51; -3.17). A number
      of trauma variables and cumulative exposure to trauma showed an association with
      physical and mental health (see main text for data). There was limited variance
      in results when each of the three models were run separately and when they were
      combined, suggesting the pervasive influence of these variables. The SF-8 showed
      good data quality and internal consistency. CONCLUSIONS: This study provides
      evidence on the pervasive influence of demographic characteristics, living
      conditions, and violent and traumatic events on the general physical and mental
      health of a conflict-affected population in Southern Sudan, and highlights the
      importance of addressing all these influences on overall health.

PMID- 20799957
TI  - Proteomic identification of secreted proteins of Propionibacterium acnes.
AB  - BACKGROUND: The anaerobic Gram-positive bacterium Propionibacterium acnes is a
      human skin commensal that resides preferentially within sebaceous follicles;
      however, it also exhibits many traits of an opportunistic pathogen, playing roles
      in a variety of inflammatory diseases such as acne vulgaris. To date, the
      underlying disease-causing mechanisms remain ill-defined and knowledge of P.
      acnes virulence factors remains scarce. Here, we identified proteins secreted
      during anaerobic cultivation of a range of skin and clinical P. acnes isolates,
      spanning the four known phylogenetic groups. RESULTS: Culture supernatant
      proteins of P. acnes were separated by two-dimensional electrophoresis (2-DE) and
      all Coomassie-stained spots were subsequently identified by MALDI mass
      spectrometry (MALDI-MS). A set of 20 proteins was secreted in the mid-exponential
      growth phase by the majority of strains tested. Functional annotation revealed
      that many of these common proteins possess degrading activities, including
      glycoside hydrolases with similarities to endoglycoceramidase, beta-N
      acetylglucosaminidase and muramidase; esterases such as lysophospholipase and
      triacylglycerol lipase; and several proteases. Other secreted factors included
      Christie-Atkins-Munch-Petersen (CAMP) factors, glyceraldehyde 3-phosphate
      dehydrogenase (GAPDH), and several hypothetical proteins, a few of which are
      unique to P. acnes. Strain-specific differences were apparent, mostly in the
      secretion of putative adhesins, whose genes exhibit variable phase variation-like
      sequence signatures. CONCLUSIONS: Our proteomic investigations have revealed that
      the P. acnes secretome harbors several proteins likely to play a role in host
      tissue degradation and inflammation. Despite a large overlap between the
      secretomes of all four P. acnes phylotypes, distinct differences between
      predicted host-tissue interacting proteins were identified, providing potential
      insight into the differential virulence properties of P. acnes isolates. Thus,
      our data presents a rich resource for guiding much-needed investigations on P.
      acnes virulence factors and host interacting properties.

PMID- 20799958
TI  - Conservation between higher plants and the moss Physcomitrella patens in response
      to the phytohormone abscisic acid: a proteomics analysis.
AB  - BACKGROUND: The plant hormone abscisic acid (ABA) is ubiquitous among land plants
      where it plays an important role in plant growth and development. In seeds, ABA
      induces embryogenesis and seed maturation as well as seed dormancy and
      germination. In vegetative tissues, ABA is a necessary mediator in the triggering
      of many of the physiological and molecular adaptive responses of the plant to
      adverse environmental conditions, such as desiccation, salt and cold. RESULTS: In
      this study, we investigated the influence of abscisic acid (ABA) on
      Physcomitrella patens at the level of the proteome using two-dimensional gel
      electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC
      MS/MS). Sixty-five protein spots showed changes in response to ABA treatment.
      Among them, thirteen protein spots were down-regulated; fifty-two protein spots
      were up-regulated including four protein spots which were newly induced. These
      proteins were involved in various functions, including material and energy
      metabolism, defense, protein destination and storage, transcription, signal
      transduction, cell growth/division, transport, and cytoskeleton. Specifically,
      most of the up-regulated proteins functioned as molecular chaperones,
      transcriptional regulators, and defense proteins. Detailed analysis of these up
      regulated proteins showed that ABA could trigger stress and defense responses and
      protect plants from oxidative damage. Otherwise, three protein kinases involved
      in signal pathways were up-regulated suggesting that P. patens is sensitive to
      exogenous ABA. The down-regulated of the Rubisco small subunit, photosystem II
      oxygen-evolving complex proteins and photosystem assembly protein ycf3 indicated
      that photosynthesis of P. patens was inhibited by ABA treatment. CONCLUSION:
      Proteome analysis techniques have been applied as a direct, effective, and
      reliable tool in differential protein expressions. Sixty-five protein spots
      showed differences in accumulation levels as a result of treatment with ABA.
      Detailed analysis these protein functions showed that physiological and molecular
      responses to the plant hormone ABA appear to be conserved among higher plant
      species and bryophytes.

PMID- 20799960
TI  - Tuberculosis of symphysis pubis in a 17 year old male: a rare case presentation
      and review of literature.
AB  - Tuberculosis of symphysis pubis is a rare condition with hardly any report of
      such cases in the last decade. It is necessary to distinguish the entity from
      more common ones like Osteitis pubis and Osteomyelitis of pubis symphysis by
      urgent means in order to start the treatment early and thereby minimize morbidity
      and prevent complications. A rare case of tuberculosis of symphysis pubis in a 17
      year old male is described. A high index of suspicion along with an extensive
      workup including 3-phase bone scan and fine needle aspiration led to the
      diagnosis. The patient had an excellent outcome following a complete course of
      multidrug chemotherapy for tuberculosis.

PMID- 20799959
TI  - Selenium hyperaccumulation offers protection from cell disruptor herbivores.
AB  - BACKGROUND: Hyperaccumulation, the rare capacity of certain plant species to
      accumulate toxic trace elements to levels several orders of magnitude higher than
      other species growing on the same site, is thought to be an elemental defense
      mechanism against herbivores and pathogens. Previous research has shown that
      selenium (Se) hyperaccumulation protects plants from a variety of herbivores and
      pathogens. Selenium hyperaccumulating plants sequester Se in discrete locations
      in the leaf periphery, making them potentially more susceptible to some herbivore
      feeding modes than others. In this study we investigate the protective function
      of Se in the Se hyperaccumulators Stanleya pinnata and Astragalus bisulcatus
      against two cell disrupting herbivores, the western flower thrips (Frankliniella
      occidentalis) and the two-spotted spider mite (Tetranychus urticae). RESULTS:
      Astragalus bisulcatus and S. pinnata with high Se concentrations (greater than
      650 mg Se kg(-1)) were less subject to thrips herbivory than plants with low Se
      levels (less than 150 mg Se kg(-1)). Furthermore, in plants containing elevated
      Se levels, leaves with higher concentrations of Se suffered less herbivory than
      leaves with less Se. Spider mites also preferred to feed on low-Se A. bisulcatus
      and S. pinnata plants rather than high-Se plants. Spider mite populations on A.
      bisulcatus decreased after plants were given a higher concentration of Se.
      Interestingly, spider mites could colonize A. bisulcatus plants containing up to
      200 mg Se kg(-1) dry weight, concentrations which are toxic to many other
      herbivores. Selenium distribution and speciation studies using micro-focused X
      ray fluorescence (MUXRF) mapping and Se K-edge X-ray absorption spectroscopy
      revealed that the spider mites accumulated primarily methylselenocysteine, the
      relatively non-toxic form of Se that is also the predominant form of Se in
      hyperaccumulators. CONCLUSIONS: This is the first reported study investigating
      the protective effect of hyperaccumulated Se against cell-disrupting herbivores.
      The finding that Se protected the two hyperaccumulator species from both cell
      disruptors lends further support to the elemental defense hypothesis and
      increases the number of herbivores and feeding modes against which Se has shown a
      protective effect. Because western flower thrips and two-spotted spider mites are
      widespread and economically important herbivores, the results from this study
      also have potential applications in agriculture or horticulture, and implications
      for the management of Se-rich crops.

PMID- 20799961
TI  - Hepatitis C virus infection in Brazilian long-distance truck drivers.
AB  - Hepatitis C virus (HCV) infection is a global public health problem. Long
      distance truck drivers live apart from their family for long periods of time, a
      lifestyle that favors at-risk behaviors such as unprotected sex with multiple
      partners and illicit drug use. As data concerning HCV infection in this
      population are still rare, this paper aims to investigate the prevalence,
      genotypes/subtypes, and the factors associated with HCV infection in long
      distance truck drivers in Brazil. A cross-sectional survey was carried out with
      641 Brazilian long-truck drivers who were recruited at a major truck stop located
      at kilometer 1,296 of the BR-153 highway, which is considered to be one of the
      longest roads in Brazil. All individuals were interviewed, and their serum
      samples were tested for the presence of antibodies to HCV (anti-HCV) by ELISA and
      immunoblot. Anti-HCV positive samples were tested for HCV RNA by PCR
      amplification of the 5' NC and NS5B regions and were genotyped using the LiPA
      assay and nucleotide sequencing, respectively. Factors associated with HCV
      infection were identified with logistic regression. The prevalence of HCV
      infection was 1.4% (95% CI: 0.7-2.8). History of blood transfusion, sharing of
      personal hygiene tools, illicit drug use and HBV status were factors
      independently associated with HCV infection in the study population. HCV RNA was
      detected in 8/9 anti-HCV positive samples, in which genotypes 1 (n = 3), 2 (n =
      2), and 3 (n = 3) were determined by LiPA. Using phylogenetic tree analysis of
      the NS5B region, subtypes 1a (n = 1), 1b (n = 2), 2b (n = 2) and 3a (n = 3) were
      identified. These data show that the prevalence of HCV infection among Brazilian
      truck drivers was similar to that observed for the general population. History of
      blood transfusion, sharing of personal hygiene tools, illicit drug use and HBV
      status were predictors of HCV infection. The HCV genotypes/subtypes identified in
      the study population are consistent with those circulating in Brazil.

PMID- 20799962
TI  - A genetic screen for replication initiation defective (rid) mutants in
      Schizosaccharomyces pombe.
AB  - In fission yeast the intra-S phase and DNA damage checkpoints are activated in
      response to inhibition of DNA replication or DNA damage, respectively. The intra
      S phase checkpoint responds to stalled replication forks leading to the
      activation of the Cds1 kinase that both delays cell cycle progression and
      stabilizes DNA replication forks. The DNA damage checkpoint, that operates during
      the G2 phase of the cell cycle delays mitotic progression through activation of
      the checkpoint kinase, Chk1. Delay of the cell cycle is believed to be essential
      to allow time for either replication restart (in S phase) or DNA damage repair
      (in G2). Previously, our laboratory showed that fission yeast cells deleted for
      the N-terminal half of DNA polymerase epsilon (Cdc20) are delayed in S phase, but
      surprisingly require Chk1 rather than Cds1 to maintain cell viability. Several
      additional DNA replication mutants were then tested for their dependency on Chk1
      or Cds1 when grown under semi-permissive temperatures. We discovered that mutants
      defective in DNA replication initiation are sensitive only to loss of Chk1,
      whilst mutations that inhibit DNA replication elongation are sensitive to loss of
      both Cds1 and Chk1. To confirm that the Chk1-sensitive, Cds1-insensitive
      phenotype (rid phenotype) is specific to mutants defective in DNA replication
      initiation, we completed a genetic screen for cell cycle mutants that require
      Chk1, but not Cds1 to maintain cell viability when grown at semi-permissive
      temperatures. Our screen identified two mutants, rid1-1 and rid2-1, that are
      defective in Orc1 and Mcm4, respectively. Both mutants show defects in DNA
      replication initiation consistent with our hypothesis that the rid phenotype is
      replication initiation specific. In the case of Mcm4, the mutation has been
      mapped to a highly conserved region of the protein that appears to be required
      for DNA replication initiation, but not elongation. Therefore, we conclude that
      the cellular response to inhibition of DNA replication initiation is distinct
      from blocking DNA replication elongation, and this difference can be exploited to
      identify mutants specifically defective in DNA replication initiation.

PMID- 20799963
TI  - Carbohydrate mouth rinse: does it improve endurance exercise performance?
AB  - It is well known that carbohydrate (CHO) supplementation can improve performance
      in endurance exercises through several mechanisms such as maintenance of glycemia
      and sparing endogenous glycogen as well as the possibility of a central nervous
      system action. Some studies have emerged in recent years in order to test the
      hypothesis of ergogenic action via central nervous system. Recent studies have
      demonstrated that CHO mouth rinse can lead to improved performance of cyclists,
      and this may be associated with the activation of brain areas linked to
      motivation and reward. These findings have already been replicated in other
      endurance modalities, such as running. This alternative seems to be an attractive
      nutritional tool to improve endurance exercise performance.

PMID- 20799964
TI  - Women's sexual health and contraceptive needs after a severe obstetric
      complication ("near-miss"): a cohort study in Burkina Faso.
AB  - BACKGROUND: Little is known about the reproductive health of women who survive
      obstetric complications in poor countries. Our aim was to determine how severe
      obstetric complications in Burkina Faso affect reproductive events in the first
      year postpartum. METHODS: Data were collected from a prospective cohort of women
      who either experienced life threatening (near-miss) pregnancy-related
      complications or an uncomplicated childbirth, followed from the end of pregnancy
      to one year postpartum or post-abortum. Documented outcomes include menses
      resumption, sexual activity resumption, dyspareunia, uptake of contraceptives,
      unmet needs for contraception and women's reproductive intentions.Participants
      were recruited in seven hospitals between December 2004 and March 2005 in six
      towns in Burkina Faso. RESULTS: Reproductive events were associated with
      pregnancy outcome. The frequency of contraceptive use was low in all groups and
      the method used varied according to the presence or not of a live baby. The
      proportion with unmet need for contraception was high and varied according to the
      time since end of pregnancy. Desire for another pregnancy was highest among near
      miss women with perinatal death or natural abortion. Women in the near-miss group
      with induced abortion, perinatal death and natural abortion had significantly
      higher odds of subsequent pregnancy. Unintended pregnancies were observed mainly
      in women in the near-miss group with live birth and the uncomplicated delivery
      group. CONCLUSIONS: Considering the potential deleterious impact (on health and
      socio-economic life) of new pregnancies in near-miss women, it is important to
      ensure family planning coverage includes those who survive a severe complication.

PMID- 20799965
TI  - Expression levels of uridine 5'-diphospho-glucuronosyltransferase genes in breast
      tissue from healthy women are associated with mammographic density.
AB  - INTRODUCTION: Mammographic density (MD), as assessed from film screen mammograms,
      is determined by the relative content of adipose, connective and epithelial
      tissue in the female breast. In epidemiological studies, a high percentage of MD
      confers a four to six fold risk elevation of developing breast cancer, even after
      adjustment for other known breast cancer risk factors. However, the biologic
      correlates of density are little known. METHODS: Gene expression analysis using
      whole genome arrays was performed on breast biopsies from 143 women; 79 women
      with no malignancy (healthy women) and 64 newly diagnosed breast cancer patients,
      both included from mammographic centres. Percent MD was determined using a
      previously validated, computerized method on scanned mammograms. Significance
      analysis of microarrays (SAM) was performed to identify genes influencing MD and
      a linear regression model was used to assess the independent contribution from
      different variables to MD. RESULTS: SAM-analysis identified 24 genes
      differentially expressed between samples from breasts with high and low MD. These
      genes included three uridine 5'-diphospho-glucuronosyltransferase (UGT) genes and
      the oestrogen receptor gene (ESR1). These genes were down-regulated in samples
      with high MD compared to those with low MD. The UGT gene products, which are
      known to inactivate oestrogen metabolites, were also down-regulated in tumour
      samples compared to samples from healthy individuals. Several single nucleotide
      polymorphisms (SNPs) in the UGT genes associated with the expression of UGT and
      other genes in their vicinity were identified. CONCLUSIONS: Three UGT enzymes
      were lower expressed both in breast tissue biopsies from healthy women with high
      MD and in biopsies from newly diagnosed breast cancers. The association was
      strongest amongst young women and women using hormonal therapy. UGT2B10 predicts
      MD independently of age, hormone therapy and parity. Our results indicate that
      down-regulation of UGT genes in women exposed to female sex hormones is
      associated with high MD and might increase the risk of breast cancer.

PMID- 20799966
TI  - The assessment, serial evaluation, and subsequent sequelae of acute kidney injury
      (ASSESS-AKI) study: design and methods.
AB  - BACKGROUND: The incidence of acute kidney injury (AKI) has been increasing over
      time and is associated with a high risk of short-term death. Previous studies on
      hospital-acquired AKI have important methodological limitations, especially their
      retrospective study designs and limited ability to control for potential
      confounding factors. METHODS: The Assessment, Serial Evaluation, and Subsequent
      Sequelae of Acute Kidney Injury (ASSESS-AKI) Study was established to examine how
      a hospitalized episode of AKI independently affects the risk of chronic kidney
      disease development and progression, cardiovascular events, death, and other
      important patient-centered outcomes. This prospective study will enroll a cohort
      of 1100 adult participants with a broad range of AKI and matched hospitalized
      participants without AKI at three Clinical Research Centers, as well as 100
      children undergoing cardiac surgery at three Clinical Research Centers.
      Participants will be followed for up to four years, and will undergo serial
      evaluation during the index hospitalization, at three months post
      hospitalization, and at annual clinic visits, with telephone interviews occurring
      during the intervening six-month intervals. Biospecimens will be collected at
      each visit, along with information on lifestyle behaviors, quality of life and
      functional status, cognitive function, receipt of therapies, interim renal and
      cardiovascular events, electrocardiography and urinalysis. CONCLUSIONS: ASSESS
      AKI will characterize the short-term and long-term natural history of AKI,
      evaluate the incremental utility of novel blood and urine biomarkers to refine
      the diagnosis and prognosis of AKI, and identify a subset of high-risk patients
      who could be targeted for future clinical trials to improve outcomes after AKI.

PMID- 20799967
TI  - Tools for delivering entomopathogenic fungi to malaria mosquitoes: effects of
      delivery surfaces on fungal efficacy and persistence.
AB  - BACKGROUND: Entomopathogenic fungi infection on malaria vectors increases daily
      mortality rates and thus represents a control measure that could be used in
      integrated programmes alongside insecticide-treated bed nets (ITNs) and indoor
      residual spraying (IRS). Before entomopathogenic fungi can be integrated into
      control programmes, an effective delivery system must be developed. METHODS: The
      efficacy of Metarhizium anisopliae ICIPE-30 and Beauveria bassiana I93-825 (IMI
      391510) (2 * 10(10) conidia m(-2)) applied on mud panels (simulating walls of
      traditional Tanzanian houses), black cotton cloth and polyester netting was
      evaluated against adult Anopheles gambiae sensu stricto. Mosquitoes were exposed
      to the treated surfaces 2, 14 and 28 d after conidia were applied. Survival of
      mosquitoes was monitored daily. RESULTS: All fungal treatments caused a
      significantly increased mortality in the exposed mosquitoes, descending with time
      since fungal application. Mosquitoes exposed to M. anisopliae conidia on mud
      panels had a greater daily risk of dying compared to those exposed to conidia on
      either netting or cotton cloth (p < 0.001). Mosquitoes exposed to B. bassiana
      conidia on mud panels or cotton cloth had similar daily risk of death (p = 0.14),
      and a higher risk than those exposed to treated polyester netting (p < 0.001).
      Residual activity of fungi declined over time; however, conidia remained
      pathogenic at 28 d post application, and were able to infect and kill 73 - 82% of
      mosquitoes within 14 d. CONCLUSION: Both fungal isolates reduced mosquito
      survival on immediate exposure and up to 28 d after application. Conidia were
      more effective when applied on mud panels and cotton cloth compared with
      polyester netting. Cotton cloth and mud, therefore, represent potential
      substrates for delivering fungi to mosquitoes in the field.

PMID- 20799968
TI  - Comprehensive modeling of microRNA targets predicts functional non-conserved and
      non-canonical sites.
AB  - mirSVR is a new machine learning method for ranking microRNA target sites by a
      down-regulation score. The algorithm trains a regression model on sequence and
      contextual features extracted from miRanda-predicted target sites. In a large
      scale evaluation, miRanda-mirSVR is competitive with other target prediction
      methods in identifying target genes and predicting the extent of their
      downregulation at the mRNA or protein levels. Importantly, the method identifies
      a significant number of experimentally determined non-canonical and non-conserved
      sites.

PMID- 20799969
TI  - Antioxidant rich grape pomace extract suppresses postprandial hyperglycemia in
      diabetic mice by specifically inhibiting alpha-glucosidase.
AB  - BACKGROUND: Postprandial hyperglycemia is an early defect of type 2 diabetes and
      one of primary anti-diabetic targets. Treatment of postprandial hyperglycemia can
      be achieved by inhibiting intestinal alpha-glucosidase, the key enzyme for
      oligosaccharide digestion and further glucose absorption. Grape pomace is
      winemaking byproduct rich in bioactive food compounds such as phenolic
      antioxidants. This study evaluated the anti-diabetic potential of two specific
      grape pomace extracts by determining their antioxidant and anti-postprandial
      hyperglycemic activities in vitro and in vivo. METHODS: The extracts of red wine
      grape pomace (Cabernet Franc) and white wine grape pomace (Chardonnay) were
      prepared in 80% ethanol. An extract of red apple pomace was included as a
      comparison. The radical scavenging activities and phenolic profiles of the pomace
      extracts were determined through the measurement of oxygen radical absorbance
      capacity, DPPH radical scavenging activity, total phenolic content and
      flavonoids. The inhibitory effects of the pomace extracts on yeast and rat
      intestinal alpha-glucosidases were determined. Male 6-week old C57BLKS/6NCr mice
      were treated with streptozocin to induce diabetes. The diabetic mice were then
      treated with vehicle or the grape pomace extract to determine whether the oral
      intake of the extract can suppress postprandial hyperglycemia through the
      inhibition of intestinal alpha-glucosidases. RESULTS: The red grape pomace
      extract contained significantly higher amounts of flavonoids and phenolic
      compounds and exerted stronger oxygen radical absorbance capacity than the red
      apple pomace extract. Both the grape pomace extracts but not the apple pomace
      extract exerted significant inhibition on intestinal alpha-glucosidases and the
      inhibition appears to be specific. In the animal study, the oral intake of the
      grape pomace extract (400 mg/kg body weight) significantly suppressed the
      postprandial hyperglycemia by 35% in streptozocin-induced diabetic mice following
      starch challenge. CONCLUSION: This is the first report that the grape pomace
      extracts selectively and significantly inhibits intestinal alpha-glucosidase and
      suppresses postprandial hyperglycemia in diabetic mice. The antioxidant and anti
      postprandial hyperglycemic activities demonstrated on the tested grape pomace
      extract therefore suggest a potential for utilizing grape pomace-derived
      bioactive compounds in management of diabetes.

PMID- 20799971
TI  - Translation reinitiation and development are compromised in similar ways by
      mutations in translation initiation factor eIF3h and the ribosomal protein RPL24.
AB  - BACKGROUND: Within the scanning model of translation initiation, reinitiation is
      a non-canonical mechanism that operates on mRNAs harboring upstream open reading
      frames. The h subunit of eukaryotic initiation factor 3 (eIF3) boosts translation
      reinitiation on the uORF-containing mRNA coding for the Arabidopsis bZip
      transcription factor, AtbZip11, among others. The RPL24B protein of the large
      ribosomal subunit, which is encoded by SHORT VALVE1, likewise fosters translation
      of uORF-containing mRNAs, for example mRNAs for auxin response transcription
      factors (ARFs). RESULTS: Here we tested the hypothesis that RPL24B and eIF3h
      affect translation reinitiation in a similar fashion. First, like eif3h mutants,
      rpl24b mutants under-translate the AtbZip11 mRNA, and the detailed spectrum of
      translational defects in rpl24b is remarkably similar to that of eif3h. Second,
      eif3h mutants display defects in auxin mediated organogenesis and gene
      expression, similar to rpl24b. Like AtbZip11, the uORF-containing ARF mRNAs are
      indeed undertranslated in eif3h mutant seedlings. CONCLUSION: We conclude that,
      similar to eIF3h, RPL24B bolsters the reinitiation competence of uORF-translating
      ribosomes. Coordination between eIF3 and the large ribosomal subunit helps to
      fine-tune translation of uORF-containing mRNAs and, in turn, to orchestrate plant
      development.

PMID- 20799970
TI  - Levels of high-density lipoprotein cholesterol (HDL-C) among children with steady
      state sickle cell disease.
AB  - BACKGROUND: The search for sickle cell disease (SCD) prognosis biomarkers is a
      challenge. These markers identification can help to establish further therapy,
      later severe clinical complications and with patients follow-up. We attempted to
      study a possible involvement of levels of high-density lipoprotein cholesterol
      (HDL-C) in steady-state children with SCD, once that this lipid marker has been
      correlated with anti-inflammatory, anti-oxidative, anti-aggregation, anti
      coagulant and pro-fibrinolytic activities, important aspects to be considered in
      sickle cell disease pathogenesis. METHODS: We prospectively analyzed biochemical,
      inflammatory and hematological biomarkers of 152 steady-state infants with SCD
      and 132 healthy subjects using immunochemistry, immunoassay and electronic cell
      counter respectively. Clinical data were collected from patient medical records.
      RESULTS: Of the 152 infants investigated had a significant positive association
      of high-density lipoprotein cholesterol with hemoglobin (P < 0.001), hematocrit
      (P < 0.001) and total cholesterol (P < 0.001) and a negative significant
      association with reticulocytes (P = 0.046), leukocytes (P = 0.015), monocytes (P
      = 0.004) and platelets (P = 0.005), bilirubins [total bilirubin (P < 0.001),
      direct bilirubin (P < 0.001) and indirect bilirubin (P < 0.001], iron (P <
      0.001), aminotransferases [aspartate aminotransferase (P = 0.004), alanine
      aminotransferase (P = 0.035)], lactate dehydrogenase (P < 0.001), urea (P =
      0.030), alpha 1-antitrypsin (P < 0.001), very low-density lipoprotein cholesterol
      (P = 0.003), triglycerides (P = 0.005) and hemoglobin S (P = 0.002). Low high
      density lipoprotein cholesterol concentration was associated with the history of
      cardiac abnormalities (P = 0.025), pneumonia (P = 0.033) and blood transfusion
      use (P = 0.025). Lipids and inflammatory markers were associated with the
      presence of cholelithiasis. CONCLUSIONS: We hypothesize that some SCD patients
      can have a specific dyslipidemic subphenotype characterized by low HDL-C with
      hypertriglyceridemia and high VLDL-C in association with other biomarkers,
      including those related to inflammation. This represents an important step toward
      a more reliable clinical prognosis. Additional studies are warranted to test this
      hypothesis and the probably mechanisms involved in this complex network of
      markers and their role in SCD pathogenesis.

PMID- 20799972
TI  - An exploratory data analysis method to reveal modular latent structures in high
      throughput data.
AB  - BACKGROUND: Modular structures are ubiquitous across various types of biological
      networks. The study of network modularity can help reveal regulatory mechanisms
      in systems biology, evolutionary biology and developmental biology. Identifying
      putative modular latent structures from high-throughput data using exploratory
      analysis can help better interpret the data and generate new hypotheses.
      Unsupervised learning methods designed for global dimension reduction or
      clustering fall short of identifying modules with factors acting in linear
      combinations. RESULTS: We present an exploratory data analysis method named MLSA
      (Modular Latent Structure Analysis) to estimate modular latent structures, which
      can find co-regulative modules that involve non-coexpressive genes. CONCLUSIONS:
      Through simulations and real-data analyses, we show that the method can recover
      modular latent structures effectively. In addition, the method also performed
      very well on data generated from sparse global latent factor models. The R code
      is available at http://userwww.service.emory.edu/~tyu8/MLSA/.

PMID- 20799973
TI  - Community based intervention to optimize osteoporosis management: randomized
      controlled trial.
AB  - BACKGROUND: Osteoporosis-related fractures are a significant public health
      concern. Interventions that increase detection and treatment of osteoporosis are
      underutilized. This pragmatic randomised study was done to evaluate the impact of
      a multifaceted community-based care program aimed at optimizing evidence-based
      management in patients at risk for osteoporosis and fractures. METHODS: This was
      a 12-month randomized trial performed in Ontario, Canada. Eligible patients were
      community-dwelling, aged >=55 years, and identified to be at risk for
      osteoporosis-related fractures. Two hundred and one patients were allocated to
      the intervention group or to usual care. Components of the intervention were
      directed towards primary care physicians and patients and included facilitated
      bone mineral density testing, patient education and patient-specific
      recommendations for osteoporosis treatment. The primary outcome was the
      implementation of appropriate osteoporosis management. RESULTS: 101 patients were
      allocated to intervention and 100 to control. Mean age of participants was 71.9
      +/- 7.2 years and 94% were women. Pharmacological treatment (alendronate,
      risedronate, or raloxifene) for osteoporosis was increased by 29% compared to
      usual care (56% [29/52] vs. 27% [16/60]; relative risk [RR] 2.09, 95% confidence
      interval [CI] 1.29 to 3.40). More individuals in the intervention group were
      taking calcium (54% [54/101] vs. 20% [20/100]; RR 2.67, 95% CI 1.74 to 4.12) and
      vitamin D (33% [33/101] vs. 20% [20/100]; RR 1.63, 95% CI 1.01 to 2.65).
      CONCLUSIONS: A multi-faceted community-based intervention improved management of
      osteoporosis in high risk patients compared with usual care. TRIAL REGISTRATION:
      This trial has been registered with clinicaltrials.gov (ID: NCT00465387).

PMID- 20799974
TI  - Lessons to be learned from a missed case of Hamate fracture: a case report.
AB  - INTRODUCTION: We report the case of a missed fracture through the body of the
      hamate bone, only detected on a later, mistakenly taken 30 degrees  oblique x-ray
      view. This case highlights some of the problems encountered with traditional x
      ray views, and the need to consider oblique views as either standard procedure or
      as an adjunct where clinical suspicion remains high even in the presence of
      normal x-rays. CASE PRESENTATION: A healthy 26-year-old Caucasian male fell
      whilst jogging, suffering a low velocity injury to his right hand. Initial
      accident and emergency examination and x-rays failed to demonstrate a fracture.
      At clinic, anteroposterior and carpal tunnel radiographs showed no fracture,
      however a mistakenly taken oblique x-ray revealed a displaced hamate body
      fracture. CONCLUSION: The authors believe that where a hamate fracture is
      suspected, an oblique x-ray view should be considered as part of the initial
      diagnostic investigations. Furthermore an oblique x-ray view is of particular use
      when clinical suspicion for hamate fracture remains high in the light of
      otherwise normal x-rays.

PMID- 20799975
TI  - Factors associated with mortality in patients with tuberculosis.
AB  - BACKGROUND: Known risk factors for death following a diagnosis of tuberculosis
      may not be applicable to current U.S. cases. We evaluated the factors associated
      with all-cause mortality in patients with tuberculosis in Washington State.
      METHODS: Using data from the Tuberculosis Information Management System of
      Washington State, we conducted a cohort study of all residents diagnosed with
      tuberculosis from 1993 through 2005. Death from any cause was ascertained through
      the Washington State Death Certificate Data Files. Proportional hazards models
      were used to estimate the independent effect on all-cause mortality of
      demographic, clinical, and behavioral characteristics. RESULTS: During a median
      follow-up of 6 years in 3451 patients treated for tuberculosis, there were 417
      deaths. Mortality was independently associated with increasing age, male gender,
      HIV-coinfection, and U.S. birth. Within 1 year of tuberculosis diagnosis,
      treatment by a private provider and the use of directly observed therapy were
      also independently associated with increased mortality. In addition, an
      interaction term of private provider times directly observed therapy was also
      significantly associated with mortality. CONCLUSIONS: We identified factors
      independently associated with increased all-cause mortality following a diagnosis
      of tuberculosis. The associations between mortality and provider type should be
      evaluated with more thorough adjustment for severity of illness, but suggest
      important directions for future research.

PMID- 20799976
TI  - Global gene expression under nitrogen starvation in Xylella fastidiosa:
      contribution of the sigma54 regulon.
AB  - BACKGROUND: Xylella fastidiosa, a Gram-negative fastidious bacterium, grows in
      the xylem of several plants causing diseases such as citrus variegated chlorosis.
      As the xylem sap contains low concentrations of amino acids and other compounds,
      X. fastidiosa needs to cope with nitrogen limitation in its natural habitat.
      RESULTS: In this work, we performed a whole-genome microarray analysis of the X.
      fastidiosa nitrogen starvation response. A time course experiment (2, 8 and 12
      hours) of cultures grown in defined medium under nitrogen starvation revealed
      many differentially expressed genes, such as those related to transport, nitrogen
      assimilation, amino acid biosynthesis, transcriptional regulation, and many genes
      encoding hypothetical proteins. In addition, a decrease in the expression levels
      of many genes involved in carbon metabolism and energy generation pathways was
      also observed. Comparison of gene expression profiles between the wild type
      strain and the rpoN null mutant allowed the identification of genes directly or
      indirectly induced by nitrogen starvation in a sigma54-dependent manner. A more
      complete picture of the sigma54 regulon was achieved by combining the
      transcriptome data with an in silico search for potential sigma54-dependent
      promoters, using a position weight matrix approach. One of these sigma54
      predicted binding sites, located upstream of the glnA gene (encoding glutamine
      synthetase), was validated by primer extension assays, confirming that this gene
      has a sigma54-dependent promoter. CONCLUSIONS: Together, these results show that
      nitrogen starvation causes intense changes in the X. fastidiosa transcriptome and
      some of these differentially expressed genes belong to the sigma54 regulon.

PMID- 20799977
TI  - Protein solubility and differential proteomic profiling of recombinant
      Escherichia coli overexpressing double-tagged fusion proteins.
AB  - BACKGROUND: Overexpression of recombinant proteins usually triggers the induction
      of heat shock proteins that regulate aggregation and solubility of the
      overexpressed protein. The two-dimensional gel electrophoresis (2-DE)-mass
      spectrometry approach was used to profile the proteome of Escherichia coli
      overexpressing N-acetyl-D-glucosamine 2-epimerase (GlcNAc 2-epimerase) and N
      acetyl-D-neuraminic acid aldolase (Neu5Ac aldolase), both fused to glutathione S
      transferase (GST) and polyionic peptide (5D or 5R). RESULTS: Overexpression of
      fusion proteins by IPTG induction caused significant differential expression of
      numerous cellular proteins; most of these proteins were down-regulated, including
      enzymes connected to the pentose phosphate pathway and the enzyme LuxS that could
      lead to an inhibition of tRNA synthesis. Interestingly, when plasmid-harboring
      cells were cultured in LB medium, gluconeogenesis occurred mainly through MaeB,
      while in the host strain, gluconeogenesis occurred by a different pathway (by Mdh
      and PckA). Significant up-regulation of the chaperones ClpB, HslU and GroEL and
      high-level expression of two protective small heat shock proteins (IbpA and IbpB)
      were found in cells overexpressing GST-GlcNAc 2-epimerase-5D but not in GST
      Neu5Ac aldolase-5R-expressing E. coli. Although most of the recombinant protein
      was present in insoluble aggregates, the soluble fraction of GST-GlcNAc 2
      epimerase-5D was higher than that of GST-Neu5Ac aldolase-5R. Also, in cells
      overexpressing recombinant GST-GlcNAc 2-epimerase-5D, the expression of sigma32
      was maintained at a higher level following induction. CONCLUSIONS: Differential
      expression of metabolically functional proteins, especially those in the
      gluconeogenesis pathway, was found between host and recombinant cells. Also, the
      expression patterns of chaperones/heat shock proteins differed among the plasmid
      harboring bacteria in response to overproduction of recombinant proteins. In
      conclusion, the solubility of overexpressed recombinant proteins could be
      enhanced by maintaining the expression of sigma32, a bacterial heat shock
      transcription factor, at higher levels during overproduction.

PMID- 20799978
TI  - Significance of Aurora B overexpression in hepatocellular carcinoma. Aurora B
      Overexpression in HCC.
AB  - BACKGROUND: To investigate the significance of Aurora B expression in
      hepatocellular carcinoma (HCC). METHODS: The Aurora B and Aurora A mRNA level was
      measured in 160 HCCs and the paired nontumorous liver tissues by reverse
      transcription-polymerase chain reaction. Mutations of the p53 and beta-catenin
      genes were analyzed in 134 and 150 tumors, respectively, by direct sequencing of
      exon 2 to exon 11 of p53 and exon 3 of beta-catenin. Anticancer effects of
      AZD1152-HQPA, an Aurora B kinase selective inhibitor, were examined in Huh-7 and
      Hep3B cell lines. RESULTS: Aurora B was overexpressed in 98 (61%) of 160 HCCs and
      in all 7 HCC cell lines examined. The overexpression of Aurora B was associated
      with Aurora A overexpression (P = 0.0003) and p53 mutation (P = 0.002) and was
      inversely associated with beta-catenin mutation (P = 0.002). Aurora B
      overexpression correlated with worse clinicopathologic characteristics.
      Multivariate analysis confirmed that Aurora B overexpression was an independent
      poor prognostic factor, despite its interaction with Aurora A overexpression and
      mutations of p53 and beta-catenin. In Huh-7 and Hep3B cells, AZD1152-HQPA induced
      proliferation blockade, histone H3 (Ser10) dephosphorylation, cell cycle
      disturbance, and apoptosis. CONCLUSION: Aurora B overexpression is an independent
      molecular marker predicting tumor invasiveness and poor prognosis of HCC. Aurora
      B kinase selective inhibitors are potential therapeutic agents for HCC treatment.

PMID- 20799979
TI  - Prevalence of chronic diseases and morbidity in primary health care in central
      Greece: an epidemiological study.
AB  - BACKGROUND: In Greece there is lack of large epidemiological studies regarding
      morbidity and mortality in primary health care. The aim of the present study was
      to estimate the prevalence and morbidity of the most common diseases in a large
      population sample from primary health care. METHODS: Four primary health centres
      were randomly selected. During one year period, 12 visits were performed in each
      centre, one per month, in random order and all visitors willing to participate in
      the study were included. Data on morbidity of each subject were recorded after
      performing an interview with the participant and checking his medical records,
      medical history and current medication. Diseases were coded using the
      international classification of primary care (ICPC) system. RESULTS: In total
      20,299 subjects were recorded. The results revealed significant variations in
      morbidity between genders and age groups. However, in all age groups, diseases of
      the circulatory system were most prevalent, followed by endocrine, metabolic,
      musculoskeletal and respiratory diseases. Osteoporosis was significantly more
      prevalent in females compared to males, whereas skin and eye disorders were more
      prevalent in subjects below 65 years old. COPD prevalence was very low compared
      to worldwide data. CONCLUSIONS: The present study revealed great variations in
      the prevalence of the diseases between genders and age groups. Our data justify
      the urgent need for the development of electronic health records that may help in
      the design of new prevention strategies in primary health care.

PMID- 20799980
TI  - Synchronous primary intrapulmonary and mediastinal thymoma--a case report.
AB  - We report an extremely rare case of Synchronous primary intrapulmonary and
      mediastinal thymoma in a Chinese patient. We describe the histological and
      radiological findings, which support the possibility of multicentric thymoma.
      Resection of the mass in the left anterior superior mediastinum and upper
      lobectomy of right lung were performed, with lymph Nodes clearance, superior vena
      cava, left and right brachiocephalic veins resection, reconstruction of left
      brachiocephalic vein to right auricle and reconstruction of right brachiocephalic
      vein to superior vena cava.

PMID- 20799981
TI  - Patient experience of access to primary care: identification of predictors in a
      national patient survey.
AB  - BACKGROUND: The 2007/8 GP Access Survey in England measured experience with five
      dimensions of access: getting through on the phone to a practice, getting an
      early appointment, getting an advance appointment, making an appointment with a
      particular doctor, and surgery opening hours. Our aim was to identify predictors
      of patient satisfaction and experience with access to English primary care.
      METHODS: 8,307 English general practices were included in the survey (of 8,403
      identified). 4,922,080 patients were randomly selected and contacted by post and
      1,999,523 usable questionnaires were returned, a response rate of 40.6%. We used
      multi-level logistic regressions to identify patient, practice and regional
      predictors of patient satisfaction and experience. RESULTS: After controlling for
      all other factors, younger people, and people of Asian ethnicity, working full
      time, or with long commuting times to work, reported the lowest levels of
      satisfaction and experience of access. For people in work, the ability to take
      time off work to visit the GP effectively eliminated the disadvantage in access.
      The ethnic mix of the local area had an impact on a patient's reported
      satisfaction and experience over and above the patient's own ethnic identity.
      However, area deprivation had only low associations with patient ratings.
      Responses from patients in small practices were more positive for all aspects of
      access with the exception of satisfaction with practice opening hours. Positive
      reports of access to care were associated with higher scores on the Quality and
      Outcomes Framework and with slightly lower rates of emergency admission.
      Respondents in London were the least satisfied and had the worst experiences on
      almost all dimensions of access. CONCLUSIONS: This study identifies a number of
      patient groups with lower satisfaction, and poorer experience, of gaining access
      to primary care. The finding that access is better in small practices is
      important given the increasing tendency for small practices to combine into
      larger units. Consideration needs to be given to ways of retaining these and
      other benefits of small practice size when primary care services are
      reconfigured. Differences between population groups (e.g. younger people, ethnic
      minorities) may be due to differences in actual care received or different
      response tendencies of different groups. Further analysis is needed to determine
      whether case-mix adjustment is required when comparing practices serving
      different populations.

PMID- 20799982
TI  - Prevalence of diagnosis and direct treatment costs of back disorders in 644,773
      children and youths in Germany.
AB  - BACKGROUND: Many authors have reported about the high prevalence rates of self
      reported back pain in children. Nevertheless, little is known about the diagnosis
      of back disorders--regardless of whether the diagnosis is associated with back
      pain or not. Therefore, the aim of this study was to analyse the prevalence rates
      and costs of diagnosis of back disorders in childhood and youth. METHODS: We
      conducted a secondary data analysis of a large, population based German data set
      (2,300,980 insurants of statutory health insurance funds) which allowed for
      identification of prevalence rates of diagnoses of back disorders in children
      (age group 0-14 years) and youths (age group 15-24 years) using three digit ICD
      10 codes for dorsopathies (M40-M54: kyphosis and lordosis; scoliosis; spinal
      osteochondrosis; other deforming dorsopathies; ankylosing spondylitis; other
      inflammatory spondylopathies; spondylosis; other spondylopathies; spondylopathies
      in diseases classified elsewhere; cervical disc disorders; other intervertebral
      disc disorders; other dorsopathies, not elsewhere classified; dorsalgia). Direct
      treatment costs were calculated based on the real incurred costs for cases with a
      singular diagnosis of a back disorder. Wherever possible, the results of the
      random sample were extrapolated to all insurants of statutory health insurance
      funds (i. e., about 90% of the German population). RESULTS: We found prevalence
      rates for the diagnosis of back disorders to range between 0.01 - 12.5%.
      "Scoliosis" (M41) and "dorsalgia" (M54) were the most frequent diagnoses in both
      age groups. Based on these results, it was calculated that in 2002 alone,
      approximately 1.4 million children/youths in Germany were diagnosed with
      "dorsalgia" (M54), and that the direct costs for back disorders in childhood and
      youth accounted for at least 100 million Euros. CONCLUSIONS: Instead of focusing
      on the individual, and self-reported disorder or disability, this analysis
      allowed for the detailed evaluation of medical experts' opinion on back disorders
      in childhood and youth and for a more objective or public health oriented insight
      in the topic of diagnosis of back pain and other back disorders. However, due to
      the methodological limitations by using ICD-10 coding, standardized random
      validity checks of population based data sets should be mandatory.

PMID- 20799983
TI  - Mechanosensitivity during lower extremity neurodynamic testing is diminished in
      individuals with Type 2 Diabetes Mellitus and peripheral neuropathy: a cross
      sectional study.
AB  - BACKGROUND: Type 2 Diabetes Mellitus (T2DM) and diabetic symmetrical
      polyneuropathy (DSP) impact multiple modalities of sensation including light
      touch, temperature, position sense and vibration perception. No study to date has
      examined the mechanosensitivity of peripheral nerves during limb movement in this
      population. The objective was to determine the unique effects T2DM and DSP have
      on nerve mechanosensitivity in the lower extremity. METHODS: This cross-sectional
      study included 43 people with T2DM. Straight leg raise neurodynamic tests were
      performed with ankle plantar flexion (PF/SLR) and dorsiflexion (DF/SLR). Hip
      flexion range of motion (ROM), lower extremity muscle activity and symptom
      profile, intensity and location were measured at rest, first onset of symptoms
      (P1) and maximally tolerated symptoms (P2). RESULTS: The addition of ankle
      dorsiflexion during SLR testing reduced the hip flexion ROM by 4.3 degrees  +/-
      6.5 degrees  at P1 and by 5.4 degrees  +/- 4.9 degrees  at P2. Individuals in the
      T2DM group with signs of severe DSP (n = 9) had no difference in hip flexion ROM
      between PF/SLR and DF/SLR at P1 (1.4 degrees  +/- 4.2 degrees ; paired t-test p =
      0.34) or P2 (0.9 degrees  +/- 2.5 degrees ; paired t-test p = 0.31). Movement
      induced muscle activity was absent during SLR with the exception of the tibialis
      anterior during DF/SLR testing. Increases in symptom intensity during SLR testing
      were similar for both PF/SLR and DF/SLR. The addition of ankle dorsiflexion
      induced more frequent posterior leg symptoms when taken to P2. CONCLUSIONS:
      Consistent with previous recommendations in the literature, P1 is an appropriate
      test end point for SLR neurodynamic testing in people with T2DM. However, our
      findings suggest that people with T2DM and severe DSP have limited responses to
      SLR neurodynamic testing, and thus may be at risk for harm from nerve overstretch
      and the information gathered will be of limited clinical value.

PMID- 20799984
TI  - The effects of air pollution on vitamin D status in healthy women: a cross
      sectional study.
AB  - BACKGROUND: Inadequate radiation or insufficient cutaneous absorption of UVB is
      one of the cardinal causes of vitamin D deficiency. The aim of this study is to
      determine whether air pollution and low ground level of ultra-violet B light
      (UVB; 290-315) can deteriorate the body vitamin D status in healthy women.
      METHODS: In this cross sectional study 200, free-living, housewives, aged between
      20 to 55 years, from Tehran (high polluted area) and Ghazvin (low polluted area)
      were included. The Tehranian women were selected randomly from participants of
      the Tehran Lipid and Glucose Study (TLGS) and the Ghazvinian females from
      patients who came to public health centers. Participants were excluded for
      disease and drugs which affect vitamin D status and also if they were pregnant or
      breast feeding. We measured the ground level of UVB using a Haze meter as a
      surrogate of air pollution. In order to calculate the adjusted mean difference of
      25-OH-D, ANCOVA analysis was used. Moreover, Binary logistic regression model was
      developed to determine the odds of living in Tehran for having serum 25-OH-D less
      than 20 ng/ml. RESULTS: The mean +/- SD of serum 25-OH-D was significantly higher
      in Ghazvinian women ((18 +/- 11 vs. 13 +/- 7), P-value < 001). The prevalence of
      25-OH-D less than 10 ng/ml, and 25-OH-D between 10 and 20 ng/ml were higher in
      Tehranian group (36% and 54% vs. 31% and 32% in respectively). Secondary
      hyperparathyroidism was also significantly higher in Tehranian women (47% vs.
      32%). In ANCOVA analysis, after adjustment, the mean of 25-OH-D in the Ghazvinian
      group was still statistically significantly higher than Tehranians (13 vs. 17
      ng/ml P-value = 0.04). In addition, in binary logistic model, the odd of living
      in Tehran for having serum 25-OH-D less than 20 ng/ml was 5.22 (95% confidence
      interval 2.2-12.2, P-value < 0.001). CONCLUSION: We found that living in a
      polluted area plays a significant independent role in vitamin D deficiency and
      hence, residence can be one of the main reasons of vitamin D status of the women.

PMID- 20799985
TI  - Detection of swine transmissible gastroenteritis coronavirus using loop-mediated
      isothermal amplification.
AB  - A conserved nucleic acid fragment of the nucleocapsid gene of Swine Transmissible
      Gastroenteritis Coronavirus (TGEV) was chosen as the target, six special primers
      were designed successfully. Loop-mediated isothermal amplification (LAMP) was
      developed to detect the TGEV by incubation at 60 degrees C for 1 h and the
      product specificity was confirmed by HphI digestion. Standard curves with high
      accuracy for TGEV quantization was constructed by adding 1 * SYBR greenI in the
      LAMP reaction. The assay established in this study was found to detect only the
      TGEV and no cross-reaction with other viruses, demonstrating its high
      specificity. By using serial sample dilutions as templates, the detection limit
      of LAMP was about 10 pg RNA, 10 times more sensitive than that of PCR and could
      be comparable to the nest-PCR.

PMID- 20799986
TI  - Are probiotics a feasible intervention for prevention of diarrhoea in the
      developing world?
AB  - With more than 1.4 million of the 9 million child deaths being attributed to
      diarrhoea in 2008 and 49% of them occurring in five countries namely, India,
      Nigeria, Democratic Republic of the Congo, Pakistan and China, there is an urgent
      need for intervention to prevent and control diarrhoeal diseases. Of the various
      interventions, probiotics offer immense potential. The past decade has witnessed
      the validation of their utility for the prevention, treatment and management of a
      variety of infective and non infective disorders. The most investigated field
      continues to remain infectious diarrhoea and compelling evidence comes from
      randomized placebo controlled trials. While results from these studies are
      encouraging most of them reflect the outcomes of the developed world. Developing
      countries like India continue to struggle with nutritional and health challenges
      and bear the greatest burden of diarrhoea. A paucity of data from the developing
      countries limits the definite recommendation of probiotics. In these countries
      curd, often confused for a probiotic, is practiced as an integral part of the
      culture. While the nutritional benefits of these products cannot be understated,
      it is still uncertain whether these products can be classified as a probiotic.
      The emergence of probiotic foods which are scientifically validated for their
      efficacy and impart defined health benefits offer an excellent opportunity to
      improve public health. A recent randomized controlled trial conducted by the
      National Institute of Cholera and Enteric Diseases in Kolkata, India demonstrated
      a protective efficacy of 14% in preventing diarrhoea among children who received
      a probiotic. For the developing world however the vision for probiotics would
      mean a fundamental change in perception and developing a well planned strategy to
      allow interventions like probiotics to permeate to impoverished settings, where
      the assault of micro organisms is on a daily basis. This would mean that
      probiotics are ingrained into the public health system without being seen as a
      medicine.

PMID- 20799988
TI  - Study of Use of Products and Exposure-Related Behaviors (SUPERB): study design,
      methods, and demographic characteristics of cohorts.
AB  - BACKGROUND: Exposure to toxic chemicals in the home is a growing concern. This
      report presents an overview of the recruitment, methods for data collection,
      instruments used to collect data, and participant demographics for a study
      examining behaviors that influence exposure to environmental toxins in the home
      environment, also known as SUPERB (Study of Use of Products and Exposure Related
      Behaviors). METHODS: The methods involved three different platforms: telephone
      interviews, internet-based surveys, and home-based monitoring. The purposes of
      SUPERB were: first, to compare data collection platforms with regard to
      feasibility, acceptability and reliability; and second, to provide longitudinal
      population-based data characterizing seasonal and long-term changes in exposure
      related behaviors including food consumption, temporal-spatial activity, and
      household product use. RESULTS: Two cohorts of households were enrolled: families
      (one parent and one child) from northern California and older individuals (age
      55+) from central California. Parents (n = 499) in Northern California families
      were on average 36 years of age, 47.1% were Latino or nonwhite, and 10.2% took
      the survey in Spanish. Most of the children enrolled (n = 566) were under 6 years
      (82.7%). The older adults enrolled (n = 156) were, on average, 66 years of age
      and 23.7% were Latino or nonwhite, but only 2.6% completed the survey in Spanish.
      CONCLUSIONS: We found that oversampling was successful in improving recruitment
      of under-represented subgroups, such as those with low education, thereby
      increasing diversity of our study sample. Protocols that minimize participant
      time, e.g., use of bar scanners and scales rather than questionnaires regarding
      use of household products, and the implementation of these protocols by staff who
      built relationships of trust, resulted in high retention over a longitudinal data
      collection scheme. A relatively small fraction of those who volunteer for
      longitudinal internet surveys are consistent in filling them out. Future reports
      will provide critical information on cross-sectional, seasonal and longitudinal
      patterns of exposure related behaviors in young children, parents of young
      children, and older adults.

PMID- 20799987
TI  - Parental socioeconomic position and development of overweight in adolescence:
      longitudinal study of Danish adolescents.
AB  - BACKGROUND: An inverse social gradient in overweight among adolescents has been
      shown in developed countries, but few studies have examined whether weight gain
      and the development of overweight differs among adolescents from different
      socioeconomic groups in a longitudinal study. The objective was to identify the
      possible association between parental socioeconomic position, weight change and
      the risk of developing overweight among adolescents between the ages 15 to 21.
      METHODS: Prospective cohort study conducted in Denmark with baseline examination
      in 1996 and follow-up questionnaire in 2003 with a mean follow-up time of 6.4
      years. A sample of 1,656 adolescents participated in both baseline (mean age
      14.8) and follow-up (mean age 21.3). Of these, 1,402 had a body mass index (BMI =
      weight/height2kg/m2) corresponding to a value below 25 at baseline when adjusted
      for age and gender according to guidelines from International Obesity Taskforce,
      and were at risk of developing overweight during the study period. The exposure
      was parental occupational status. The main outcome measures were change in BMI
      and development of overweight (from BMI < 25 to BMI > = 25). RESULTS: Average BMI
      increased from 21.3 to 22.7 for girls and from 20.6 to 23.6 in boys during follow
      up. An inverse social gradient in overweight was seen for girls at baseline and
      follow-up and for boys at follow-up. In the full population there was a tendency
      to an inverse social gradient in the overall increase in BMI for girls, but not
      for boys. A total of 13.4% developed overweight during the follow-up period.
      Girls of lower parental socioeconomic position had a higher risk of developing
      overweight (OR's between 4.72; CI 1.31 to 17.04 and 2.03; CI 1.10-3.74) when
      compared to girls of high parental socioeconomic position. A tendency for an
      inverse social gradient in the development of overweight for boys was seen, but
      it did not meet the significance criteria CONCLUSIONS: The levels of overweight
      and obesity among adolescents are high and continue to rise. Results from this
      study suggest that the inverse social gradient in overweight becomes steeper for
      girls and emerges for boys in late adolescence (age span 15 to 21 years). Late
      adolescence seems to be an important window of opportunity in reducing the social
      inequality in overweight among Danish adolescents.

PMID- 20799989
TI  - Bisphosphonate treatment of aggressive primary, recurrent and metastatic Giant
      Cell Tumour of Bone.
AB  - BACKGROUND: Giant cell tumour of bone (GCTB) is an expansile osteolytic tumour
      which contains numerous osteoclast-like giant cells. GCTB frequently recurs and
      can produce metastatic lesions in the lungs. Bisphosphonates are anti-resorptive
      drugs which act mainly on osteoclasts. METHOD: In this study, we have examined
      clinical and radiological outcomes of treatment with aminobisphosphonates on 25
      cases of aggressive primary, recurrent and metastatic GCTB derived from four
      European centres. We also analysed in vitro the inhibitory effect of zoledronic
      acid on osteoclasts isolated from GCTBs. RESULTS: Treatment protocols differed
      with several different aminobisphosphonates being employed, but stabilisation of
      disease was achieved in most of these cases which were refractory to conventional
      treatment. Most inoperable sacral/pelvic tumours did not increase in size and no
      further recurrence was seen in GCTBs that had repeatedly recurred in bone and
      soft tissues. Lung metastases did not increase in size or number following
      treatment. Zoledronic acid markedly inhibited lacunar resorption by GCTB-derived
      osteoclasts in vitro. CONCLUSION: Our findings suggest that bisphosphonates may
      be useful in controlling disease progression in GCTB and that these agents
      directly inhibit GCTB - derived osteoclast resorption. These studies highlight
      the need for the establishment of standardised protocols to assess the efficacy
      of bisphosphonate treatment of GCTB.

PMID- 20799990
TI  - Mothers and daughters-in-law: a prospective study of informal care-giving
      arrangements and survival in Japan.
AB  - BACKGROUND: Daughters-in-law have played an important role in informal care
      giving arrangements within East Asian traditional norms. The aim of this study
      was to measure the impact of daughter-in-law care-giving on the survival of care
      recipients. We prospectively examined the associations between different types of
      kinship relationship between the main family caregiver and the care recipient in
      relation to survival among care recipients. METHODS: A questionnaire was
      administered to Japanese community-dwelling seniors who were eligible to receive
      national long-term care insurance (LTCI) community-based services. Among 191
      individuals whose informal care-giving arrangement was definitively determined,
      we observed 58 care recipients receiving care from spouses, 58 from daughters-in
      law, 27 from biological daughters, 25 from other relatives, and 23 care
      recipients living alone. RESULTS: During 51 months of follow-up from December
      2001, 68 care recipients died, 117 survived, and 6 moved. Hazard ratios of each
      care-giving arrangement were estimated by Cox proportional hazard models adjusted
      for care recipients' demographic factors, their care needs level based on their
      physical and cognitive functioning and their service use, caregivers' demographic
      factors, and household size. The highest risk of mortality was found for female
      elders receiving care from daughters-in-law (HR 4.15, 95% CI 1.02-16.90) followed
      by those receiving care from biological daughters (HR 1.64, 95% CI 0.37-7.21),
      compared to women receiving spousal care. By contrast, male elders receiving care
      from daughters-in-law tended to live longer than those receiving care from their
      spouses. CONCLUSIONS: Our finding suggests that there may be a survival "penalty"
      for older Japanese women who are cared for by their daughters-in-law.

PMID- 20799991
TI  - A mid term comparison of open wedge high tibial osteotomy vs unicompartmental
      knee arthroplasty for medial compartment osteoarthritis of the knee.
AB  - BACKGROUND: The choice of surgical treatments for unicompartmental osteoarthritis
      (OA) of the knee is still somewhat controversial. Midterm results from cases
      treated using unicompartmental knee arthroplasty (UKA) or open wedge high tibial
      osteotomy (OWHTO) were evaluated retrospectively. METHODS: Twenty-seven knees of
      24 patients with varus deformities underwent OWHTO and 30 knees of 18 patients
      underwent UKA surgeries for the treatment of medial compartmental osteoarthritis
      (OA). The KSS score, FTA, range of motion and complications were evaluated before
      and after surgery. RESULTS: The preoperative mean KSS scores were 49 points in
      the OWHTO group and 62 in the UKA group which improved postoperatively to 89
      (excellent; 19 knees, good; 8 knees), and 88 (excellent; 25, good; 4, fair; 1),
      respectively. There was no significant difference between the OWHTO and UKA
      scores. Seventeen patients in the OWHTO group could sit comfortably in the formal
      Japanese style after surgery. The preoperative mean FTA values for the OWHTO and
      UKA groups were 182 degrees and 184, and at follow-up measured 169 and 170,
      respectively. In the UKA group, the femoral component and the polyethylene
      insertion in one patient was exchanged at 5 years post-surgery and revision TKAs
      were performed in 2 cases. In the OWHTO group, one tibial plateau fracture and
      one subcutaneous tissue infection were noted. CONCLUSIONS: Treatment options
      should be carefully considered for each OA patient in accordance with their
      activity levels, grade of advanced OA, age, and range of motion of the knee.
      OWHTO shows an improved indication for active patients with a good range of
      motion of the knee.

PMID- 20799992
TI  - The adenosine A2A receptor is associated with methamphetamine
      dependence/psychosis in the Japanese population.
AB  - BACKGROUND: Several lines of evidence suggest that the dopaminergic nervous
      system contributes to methamphetamine (METH) dependence, and there is increasing
      evidence of antagonistic interactions between dopamine and adenosine receptors.
      We therefore hypothesized that variations in the A2A adenosine receptor (ADORA2A)
      gene modify genetic susceptibility to METH dependence/psychosis. METHODS: We
      first analyzed variations in the exons and exon-intron boundaries of the ADORA2A
      gene in METH dependent/psychotic patients. Then an association analysis between
      these single nucleotide polymorphisms and METH dependence/psychosis was performed
      using a total of 171 METH dependent/psychotic patients and 229 controls. RESULTS:
      We found 6 variations, of which one single nucleotide polymorphism (SNP) was
      novel. Significant associations were observed between the allelic and genotypic
      frequencies of the Exon2+751 (rs5751876) SNP and METH dependence/psychosis. These
      associations were observed especially in females. In the clinical feature
      analyses, significant associations were observed between the SNP and the patient
      subgroup using METH alone (i.e., without concomitant use of other substances of
      abuse). CONCLUSIONS: These results suggest that the ADORA2A gene could be a
      vulnerability factor for METH dependence/psychosis, especially in females and/or
      in patients using only METH.

PMID- 20799993
TI  - Health-related quality of life in Parkinson disease: correlation between Health
      Utilities Index III and Unified Parkinson's Disease Rating Scale (UPDRS) in U.S.
      male veterans.
AB  - OBJECTIVE: To apply a scaled, preference-based measure to the evaluation of
      health-related quality of life (HRQoL) in Parkinson's disease (PD); to evaluate
      the relationship between disease-specific rating scales and estimated HRQoL; and
      to identify predictors of diminished HRQoL. BACKGROUND: Scaled, preference-based
      measures of HRQoL ("utilities") serve as indices of impact of disease, and can be
      used to generate quality-adjusted estimates of survival for health-economic
      evaluations. Evaluation of utilities for PD and their correlation with standard
      rating scales have been limited. METHODS: Utilities were generated using the
      Health Utilities Index Mark III (HUI-III) on consecutive patients attending a PD
      Clinic between October 2003 and June 2006. Disease severity, medical, surgical
      (subthalamic nucleus deep brain stimulation (STN-DBS)), and demographic
      information were used as model covariates. Predictors of HUI-III utility scores
      were evaluated using the Wilxocon rank-sum test and linear regression models.
      RESULTS: 68 men with a diagnosis of PD and a mean age of 74.0 (SD 7.4) were
      included in the data analysis. Mean HUI-III utility at first visit was 0.45 (SD
      0.33). In multivariable models, UPDRS-II score (r2 = 0.56, P < 0.001) was highly
      predictive of HRQoL. UPDRS-III was a weaker, but still significant, predictor of
      utility scores, even after adjustment for UPDRS-II (P = 0.01). CONCLUSIONS: Poor
      self-care in PD reflected by worsening UPDRS-II scores is strongly correlated
      with low generic HRQoL. HUI-III-based health utilities display convergent
      validity with the UPDRS-II. These findings highlight the importance of measures
      of independence as determinants of HRQoL in PD, and will facilitate the
      utilization of existing UPDRS data into economic analyses of PD therapies.

PMID- 20799994
TI  - Anti-tumor effects of CIK combined with oxaliplatin in human oxaliplatin
      resistant gastric cancer cells in vivo and in vitro.
AB  - BACKGROUND: Drug resistance remains a great challenge in the treatment of gastric
      cancer. The goal of this study was to explore the anti-tumor effects and
      mechanism of cytokine-induced killer (CIK) cell combined with oxaliplatin (L-OHP)
      in human oxaliplatin-resistant gastric cancer cells. METHODS: After producing
      oxaliplatin-resistant gastric cancer cells, cell morphology, growth and doubling
      time were observed, followed by detection of cell cycle distribution and
      apoptosis, drug sensitivity (e.g., L-OHP) and expression of P-gp and livin. MTT
      assay, in vivo pharmacodynamics and pathomorphology experiments were used to
      detect killing activities of CIK combined with L-OHP. RESULTS: Compared with
      parental gastric cancer cells, oxaliplatin-resistant gastric cancer cells in S
      phase were reduced and cell apoptosis rate was increased (P < 0.05), the
      inhibition rate of 10 chemotherapeutics on oxaliplatin-resistant gastric cancer
      cells was significantly lower and the expression of P-gp was significantly higher
      (P < 0.05). However, there was no significant difference in livin expression
      between parental gastric cancer cells and oxaliplatin-resistant gastric cancer
      cells (P > 0.05). The in vitro killing activity of CIK combined with L-OHP on
      parental cells and oxaliplatin-resistant cells were significantly enhanced
      compared with L-OHP or CIK alone. And it showed greater synergetic effects
      against oxaliplatin-resistant cells compared with parental cells (P < 0.05). In
      addition, survival rate, abdominal circumference and pathomorphology results
      revealed stronger in vivo anti-tumor effects when the two therapies were
      combined. CONCLUSIONS: The mechanism of oxaliplatin-resistant cell secondary
      multidrug resistance was correlated with the variation of cell cycle
      distribution, extension of doubling time and upregulation of P-gp expression. The
      synergistic effect of CIK in combination with L-OHP on killing activity against
      oxaliplatin-resistant cells was shown in vivo and in vitro.

PMID- 20799996
TI  - Wash durability and optimal drying regimen of four brands of long-lasting
      insecticide-treated nets after repeated washing under tropical conditions.
AB  - BACKGROUND: The current study was undertaken to determine the optimal wash-drying
      regimen and the effects of different washing procedures on the efficacy, and
      durability of four brands of newly introduced long-lasting insecticide-treated
      nets (LLINs) under tropical conditions. METHODS: In the current study, the
      following four LLINs were tested: Olyset, PermaNet 2.0, BASF and TNT. Nets were
      divided into three sets; one set was washed by hand rubbing and air-dried either
      hanging or spread on the ground in direct sunlight or hanging or spread on the
      ground under the shade. A second set was washed using the WHO protocol (machine)
      and the third set was washed by beating the nets on rocks. The biological
      activities of the nets were assessed by a three-minute bioassay cone test and the
      residual insecticide contents were determined using high performance liquid
      chromatography (HPLC) procedure. RESULTS: Nets that were dried hanging under the
      shade retained more insecticide, 62.5% and recorded higher mortality compared to
      nets which were dried lying on the ground in direct sunlight 58.8%, nets dried
      under the shade spread on the ground 56.3%, and 57.8% for nets dried hanging in
      direct sunlight. It was also observed that nets washed by the standard WHO
      protocol, retained more insecticide and were more effective in killing mosquitoes
      compared to nets washed by local methods of hand rubbing and beating on rocks.
      There were significant differences between drying regimens (p < 0.0001) and
      between washing procedures (p < 0.001) respectively. However, the effect of net
      type was statistically insignificant. The statistical differences on individual
      nets were also compared, for PermaNet and TNT there were no significant
      differences observed between the four drying regimens (p = 0.7944 and 0.4703)
      respectively). For BASF and Olyset, the differences were significant (p < 0.001
      and p > 0.0001). CONCLUSION: The results of this study suggest that washing and
      drying regimen influence the insecticidal activity of LLINs. The standard WHOPES
      washing protocol underestimates the amount of insecticide washed from LLINs
      compared to the abrasive washing procedures that are used in the field. This
      suggests that there is need to educate net users to adopt a more gentle washing
      procedure while handling LLINs. The education should accompany net distribution
      campaigns.

PMID- 20799997
TI  - Sleep disorders: diagnosis and treatment. Foreword.

PMID- 20799995
TI  - Anti-folate drug resistance in Africa: meta-analysis of reported dihydrofolate
      reductase (dhfr) and dihydropteroate synthase (dhps) mutant genotype frequencies
      in African Plasmodium falciparum parasite populations.
AB  - BACKGROUND: Mutations in the dihydrofolate reductase (dhfr) and dihydropteroate
      synthase (dhps) genes of Plasmodium falciparum are associated with resistance to
      anti-folate drugs, most notably sulphadoxine-pyrimethamine (SP). Molecular
      studies document the prevalence of these mutations in parasite populations across
      the African continent. However, there is no systematic review examining the
      collective epidemiological significance of these studies. This meta-analysis
      attempts to: 1) summarize genotype frequency data that are critical for molecular
      surveillance of anti-folate resistance and 2) identify the specific challenges
      facing the development of future molecular databases. METHODS: This review
      consists of 220 studies published prior to 2009 that report the frequency of
      select dhfr and dhps mutations in 31 African countries. Maps were created to
      summarize the location and prevalence of the highly resistant dhfr triple mutant
      (N51I, C59R, S108N) genotype and dhps double mutant (A437G and K540E) genotype in
      Africa. A hierarchical mixed effects logistic regression was used to examine the
      influence of various factors on reported mutant genotype frequency. These factors
      include: year and location of study, age and clinical status of sampled
      population, and reporting conventions for mixed genotype data. RESULTS: A
      database consisting of dhfr and dhps mutant genotype frequencies from all African
      studies that met selection criteria was created for this analysis. The map
      illustrates particularly high prevalence of both the dhfr triple and dhps double
      mutant genotypes along the Kenya-Tanzania border and Malawi. The regression model
      shows a statistically significant increase in the prevalence of both the dhfr
      triple and dhps double mutant genotypes in Africa. CONCLUSION: Increasing
      prevalence of the dhfr triple mutant and dhps double mutant genotypes in Africa
      are consistent with the loss of efficacy of SP for treatment of clinical malaria
      in most parts of this continent. Continued assessment of the effectiveness of SP
      for the treatment of clinical malaria and intermittent preventive treatment in
      pregnancy is needed. The creation of a centralized resistance data network, such
      as the one proposed by the WorldWide Antimalarial Resistance Network (WWARN),
      will become a valuable resource for planning timely actions to combat drug
      resistant malaria.

PMID- 20799998
TI  - Obstructive sleep apnea: diagnosis, epidemiology, and economics.
AB  - Obstructive sleep apnea (OSA) is a disorder characterized by intermittent upper
      airway collapse, which impairs ventilation and disrupts sleep. Factors that
      contribute to upper-airway collapse include reduced upper-airway dilator muscle
      activity during sleep, specific upper-airway anatomical features, decreased end
      expiratory lung volume, ventilatory control instability, sleep-state instability,
      and rostral fluid shifts in the recumbent position. The relative contributions of
      these factors vary between individuals with OSA, and this may have implications
      as to which treatments are efficacious for an individual. OSA is common in
      adults; males, older individuals, and the obese are at higher risk. There is
      uncertainty in how to measure severity of sleep-disordered breathing, what cut
      off to use to demarcate abnormal, and how to define the clinical syndrome.
      Identifying patients at higher risk who should have a sleep study is relatively
      simple, involving assessment of several factors, such as snoring, witnessed
      apnea/self-reported gasping, hypertension, body mass index, and neck
      circumference. As would be expected from a disorder that causes morbidity, OSA is
      associated with substantial economic costs to society, including increased
      medical costs. A reduction in medical costs in a diverse adult patient population
      with OSA after therapy has not been convincingly demonstrated. Nevertheless, the
      results of cost-effectiveness analyses strongly support the cost-effectiveness of
      continuous positive airway pressure therapy in patients with moderate to severe
      OSA, relative to other standard medical therapies that society is willing to pay
      for.

PMID- 20800000
TI  - What every clinician should know about polysomnography.
AB  - Polysomnography studies are an essential tool for the sleep physician and aid in
      the diagnosis and treatment of sleep disorders. Polysomnography refers to the
      recording, analysis, and interpretation of multiple physiologic signals collected
      simultaneously. Rapid advancements in technology have transformed the field from
      a time when analog studies were collected on paper to computer-assisted
      collection of digitally transformed studies. Sleep clinicians, whether
      physicians, respiratory therapists, or sleep technologists, must therefore have
      an understanding of a broad array of principles underlying the collection of the
      various signals. In addition, an understanding of basic technical rules in the
      evaluation of polysomnography studies is necessary for both the scoring and
      interpretation of such studies. The American Academy of Sleep Medicine published
      a new manual for the scoring of sleep and associated events in 2007. These
      changes included modifications to the visual scoring of sleep, the scoring of
      sleep-disordered breathing events, and movement disorders during sleep. A few
      early studies have evaluated the effects of the changes in scoring guidelines to
      the previous Rechtschaffen and Kales (R&K) rules for sleep and the American
      Academy of Sleep Medicine rules for respiratory events. Some controversy
      regarding the scoring of respiratory events continues to exist and requires
      further studies to be performed.

PMID- 20799999
TI  - What is central sleep apnea?
AB  - Central sleep apnea (CSA) describes a group of conditions in which cessations in
      air flow occur without respiratory effort. In contrast, obstructive sleep apnea
      patients have ongoing respiratory effort during respiratory events. However,
      considerable overlap exists in the pathogenesis and clinical presentation of
      obstructive sleep apnea and CSA. A good working knowledge of the mechanisms
      underlying CSA is important for optimal clinical care. In general, CSA can be
      classified into those with excessive drive (eg, Cheyne-Stokes breathing) versus
      those with inadequate drive (eg, sleep hypoventilation syndrome). One critical
      factor contributing to the cessation of air flow during sleep is the concept of
      the apnea threshold, such that a P(aCO(2)) value below a certain level will lead
      to cessations in breathing. P(aCO(2)) can fall below the chemical apnea threshold
      when drive is excessive (eg, robust chemosensitivity) or when hyperventilation is
      occurring (eg, following arousal). Another important factor is the loss of the so
      called wakefulness drive to breathe, such that some rise in P(aCO(2)) is likely
      to occur at the onset of sleep. A variety of factors contribute to this rise,
      including upper-airway collapse and diminished chemosensitivity (particularly
      during rapid-eye-movement sleep). In patients with low central drive, this
      further loss of drive at sleep onset can lead to marked hypercapnia in some
      cases. The treatment of CSA is also reviewed in some detail, including a role for
      positive airway pressure (eg, bi-level positive airway pressure in
      hypoventilation patients) and optimization of medical therapy (eg, in Cheyne
      Stokes breathing). A paucity of research exists in this area, emphasizing the
      opportunities for young investigators who are interested in this field.

PMID- 20800001
TI  - Portable-monitor testing: an alternative strategy for managing patients with
      obstructive sleep apnea.
AB  - Portable-monitor testing is being used increasingly in ambulatory management
      pathways for the diagnosis and treatment of patients with obstructive sleep
      apnea. Wide varieties of portable monitors are commercially available and they
      range from single-channel recorders to units that record a full polysomnogram.
      Recent comparative effectiveness research studies have shown that clinical
      outcomes of patients with a high pretest probability for obstructive sleep apnea
      who receive ambulatory management using portable-monitor testing have similar
      functional outcomes and adherence to continuous positive airway pressure
      treatment, compared to patients managed with in-laboratory polysomnography. The
      cost-effectiveness of portable-monitor testing and its potential to improve
      patient access to diagnosis and treatment requires further investigation.

PMID- 20800003
TI  - Encouraging CPAP adherence: it is everyone's job.
AB  - Obstructive sleep apnea (OSA) is a chronic disease treated effectively with the
      use of continuous positive airway pressure (CPAP) therapy. Patient adherence to
      prescribed CPAP is variable, however, leaving the undertreated OSA patient at
      risk of development or worsening of comorbid medical conditions, including
      hypertension and cardiovascular disease. The severity of disease and the presence
      of daytime sleepiness appear to have some predictive quality for subsequent
      adherence, though a search for consistent predictive factors related to CPAP
      adherence has proven elusive. Other influences, such as sex, age, socioeconomic
      status, and personality traits are less robust predictors. The use of
      sophisticated therapy modalities such as auto-titration or bi-level PAP units has
      been shown to improve adherence in certain subsets of OSA patients. Adverse
      effects such as nasal congestion, dry mouth, or skin irritation occur in
      approximately 50% of CPAP users, and addressing these adverse effects may improve
      adherence in some patients. More encouraging, studies on the use of intensive
      patient education and behavioral interventions have shown more positive effects
      on adherence, leading to the conclusion that improvement in patient adherence to
      CPAP therapy requires a multi-layered approach, using combined technological,
      behavioral, and adverse-effect interventions.

PMID- 20800002
TI  - CPAP and bi-level PAP therapy: new and established roles.
AB  - Over the past few decades, continuous positive airway pressure (CPAP) therapy for
      obstructive sleep apnea has evolved into more and more sophisticated modes of
      therapy for various forms of sleep-disordered breathing. While the principles of
      splinting the airway and delivering assisted ventilation underpin the basics of
      this therapy, the introduction of newer technologies and miniaturization are
      revolutionizing the former conventions of the field. The purpose of this review
      is to improve our understanding of various forms of PAP therapy by providing the
      rationale for such modalities, gaining a basic working knowledge of device
      technology, and critically assessing the clinical research evidence while
      identifying barriers to implementation. Dissemination of such information is
      vital in order to prevent knowledge gaps in healthcare providers and systems.

PMID- 20800004
TI  - Sleep and sleep-disordered breathing in the hospitalized patient.
AB  - Clinicians are becoming more aware of the risks of sleep deprivation and
      unrecognized sleep-disordered breathing in hospitalized patients, most
      importantly in those patients planning to undergo surgical procedures.
      Polysomnography is difficult to perform in the hospital setting, such that
      actigraphy or urinary metabolites of melatonin are often used as surrogate
      measures, and show that sleep is markedly impaired. Patients in the medical
      intensive care unit with sepsis or requiring mechanical ventilation may show
      complete absence of the normal circadian rhythm pattern, and many centers have
      initiated sleep-enhancement protocols. In postoperative patients, rapid-eye
      movement sleep is nearly obliterated, especially in the first 1-2 days after
      surgery, and this appears closely related to the use of high-dose opioids. Sleep
      disordered breathing is common in postoperative patients, and tools such as the
      Sleep Apnea Clinical Score or the STOP-BANG (Snoring, Tiredness, Observed apnea,
      and high blood Pressure - Body mass index, Age, Neck circumference, and Gender)
      questionnaires have been utilized to predict the possibility of obstructive sleep
      apnea (OSA) and postoperative respiratory complications. Protocols to evaluate
      patients that determine the need and process for positive-airway-pressure
      treatment in the hospital patient with OSA are being developed. An obstructive
      apnea systematic intervention strategy protocol to deal with patients with
      suspected OSA can help guide diagnostic and therapeutic decision making.
      Hospitals that are proactive in the development of protocols for identification
      and management of patients with sleep-disordered breathing are likely to be
      rewarded with reduced complications and costs, and the issue is sure to be
      incorporated in future pay-for-performance evaluations.

PMID- 20800005
TI  - Concentrations of bovine lactoferrin and citrate in milk during experimental
      endotoxin mastitis in early- versus late-lactating dairy cows.
AB  - Lactoferrin (Lf) is a molecule naturally present in bovine milk that affects the
      availability and transport systems of iron. Lf also binds endotoxin
      (lipopolysaccharide, LPS) of Gram-negative bacteria and modulates the
      immunological response. In the present study, concentrations of bovine Lf (bLf)
      and citrate in milk were determined in early (EL) and late (LL) lactating dairy
      cows, using an experimentally induced endotoxin mastitis model and a crossover
      design. Nine clinically healthy Finnish Ayrshire cows were challenged twice with
      100 MUg endotoxin infused into one udder quarter. Milk samples were collected
      from the challenged and control quarters of each cow before and after endotoxin
      infusion during 3 d, and bLf and citrate concentrations were measured. In all
      cows, clinical signs of mastitis were seen at both times of challenge, but the
      response was more severe in EL than in LL. Concentration of bLf in the milk
      started to rise approximately 8 h after endotoxin infusion and was still higher
      than normal on the third day, especially in the late-lactating cows. In milk of
      the LL group, concentrations of bLf were significantly higher than in the EL
      group. In contrast, concentrations of citrate were higher in milk of the EL cows
      compared with the LL cows. Concentration of bLf and citrate varied substantially
      among cows. The molar ratio of citrate to bLf before and after challenge was
      significantly higher during the EL period. The results of this study partly
      explain why cows in early lactation are more susceptible to intramammary
      infections and why mastitis is more severe in them.

PMID- 20800006
TI  - Sporadic Cryptosporidium infection in Nigerian children: risk factors with
      species identification.
AB  - A cross-sectional study was conducted to investigate risk factors for sporadic
      Cryptosporidium infection in a paediatric population in Nigeria. Of 692 children,
      134 (19.4%) were infected with Cryptosporidium oocysts. Cryptosporidium spp. were
      identified in 49 positive samples using PCR-restriction fragment length
      polymorphism and direct sequencing of the glycoprotein60 (GP60) gene. Generalized
      linear mixed-effects models were used to identify risk factors for all
      Cryptosporidium infections, as well as for C. hominis and C. parvum both together
      and separately. Risk factors identified for all Cryptosporidium infections
      included malaria infection and a lack of Ascaris infection. For C. hominis
      infections, stunting and younger age were highlighted as risk factors, while
      stunting and malaria infection were identified as risk factors for C. parvum
      infection.

PMID- 20800007
TI  - Nosocomial outbreak of Crimean-Congo haemorrhagic fever.
AB  - We report a nosocomial outbreak of Crimean-Congo haemorrhagic fever (CCHF) that
      affected six patients in June 2009 in Ghaem Hospital, Mashhad, Iran, apparently
      related to one index case. The last four cases were healthcare workers. Infection
      was spread by percutaneous exposure to two cases, and probably by direct contact
      with blood, clothes and sheets, to three others. The diagnosis in the two fatal
      cases was not confirmed virologically. The diagnosis in four cases who survived
      was confirmed by specific reverse transcription polymerase chain reaction. The
      patients were treated with ribavirin. In endemic areas, every patient presenting
      with a febrile haemorrhagic syndrome should be considered to have a viral
      haemorrhagic fever until proven otherwise. Patients who meet the criteria for
      probable CCHF should be admitted to hospital and treated with ribavirin.
      Appropriate isolation precautions should be immediately initiated.

PMID- 20800008
TI  - Changes in knowledge, perceptions, preventive behaviours and psychological
      responses in the pre-community outbreak phase of the H1N1 epidemic.
AB  - To investigate the changes in community responsiveness during the pre-community
      outbreak phase of the H1N1 epidemic in Hong Kong, a pooled sample of 999 adults
      was interviewed in three surveys (S1, S2, S3) from 7 May to 6 June 2009. Over
      time, fewer people felt confident in staying free from H1N1 infection in the
      following year (S1, 63.3%; S3, 46%; P<0.001). The level of distress due to H1N1
      remained modest throughout the study period. People's confidence in the
      government's ability to control a large-scale H1N1 outbreak declined slightly at
      the third survey (S1, 80.5%; S3, 73.8%; P=0.025). Across the three surveys,
      respondents remained vigilant with frequent adoption of preventive measures (e.g.
      wearing face masks in public areas when suffering from influenza-like symptoms
      and frequent hand-washing). The public was generally supportive of the Hong Kong
      government although misconceptions regarding the disease were common. Provision
      of evidence-based public-health education is still warranted as the disease
      outbreak unfolds.

PMID- 20800009
TI  - An outbreak of Salmonella Paratyphi A in a boarding school: a community-acquired
      enteric fever and carriage investigation.
AB  - Salmonella Paratyphi A (SPA) is rapidly becoming a common cause of enteric fever
      in South East Asia. A large outbreak of SPA occurred in a boarding middle school
      in China in 2004. There were 394 suspected cases; 95.5% were students. The
      highest incidence was in the youngest children (7th grade). Forty-four of 151
      (29%) blood cultures and 4/54 (7.4%) rectal swabs were positive for SPA; three
      were from kitchen workers. The geometric mean levels of serum IgG anti
      lipopolysaccharide (anti-LPS) from patients was higher than from healthy
      individuals [35.25 vs. 5.20 ELISA units (EU), P<0.001]. A kitchen worker with a
      positive rectal swab, negative blood culture and a high level of serum IgG anti
      LPS (529.65 EU), was identified as a possible SPA carrier. No SPA was isolated
      from water or food samples. A survey of students' habits indicated drinking
      unboiled water as being the main reason for contracting the disease. Hand washing
      was the second most important factor. A food handler with possible SPA carriage
      could also have been a risk factor. Attention to maintaining a safe water supply,
      enhancing food-handler hygiene and proper hand washing can help to prevent
      similar outbreaks in the future.

PMID- 20800010
TI  - The astacin metalloprotease moulting enzyme NAS-36 is required for normal cuticle
      ecdysis in free-living and parasitic nematodes.
AB  - Nematodes represent one of the most abundant and species-rich groups of animals
      on the planet, with parasitic species causing chronic, debilitating infections in
      both livestock and humans worldwide. The prevalence and success of the nematodes
      is a direct consequence of the exceptionally protective properties of their
      cuticle. The synthesis of this cuticle is a complex multi-step process, which is
      repeated 4 times from hatchling to adult and has been investigated in detail in
      the free-living nematode, Caenorhabditis elegans. This process is known as
      moulting and involves numerous enzymes in the synthesis and degradation of the
      collagenous matrix. The nas-36 and nas-37 genes in C. elegans encode functionally
      conserved enzymes of the astacin metalloprotease family which, when mutated,
      result in a phenotype associated with the late-stage moulting defects, namely the
      inability to remove the preceding cuticle. Extensive genome searches in the
      gastrointestinal nematode of sheep, Haemonchus contortus, and in the filarial
      nematode of humans, Brugia malayi, identified NAS-36 but not NAS-37 homologues.
      Significantly, the nas-36 gene from B. malayi could successfully complement the
      moult defects associated with C. elegans nas-36, nas-37 and nas-36/nas-37 double
      mutants, suggesting a conserved function for NAS-36 between these diverse
      nematode species. This conservation between species was further indicated when
      the recombinant enzymes demonstrated a similar range of inhibitable
      metalloprotease activities.

PMID- 20800011
TI  - Genetic diversity of Babesia in Ixodes persulcatus and small mammals from North
      Ural and West Siberia, Russia.
AB  - OBJECTIVE: The aim of this work was to study the prevalence and genetic diversity
      of Babesia in Ixodes persulcatus ticks and small mammals from Ural and Siberia in
      Russia. METHODS: In total, 481 small mammals and 922 questing adult I.
      persulcatus from North Ural (Sverdlovsk region) and West Siberia (Novosibirsk
      region) were examined for the presence of Babesia by nested PCR based on the 18S
      rRNA gene. RESULTS: Babesia microti of the 'Munich'-type was found in 36.2% of
      blood samples of the small mammals from the Sverdlovsk region and B. microti of
      the 'US'-type in 5.3% of the animals from the Novosibirsk region. Babesia DNA was
      not detected in 133 analysed I. persulcatus from the Sverdlovsk region; however,
      it was found in 24 of 789 ticks from the Novosibirsk region. Three distinct
      Babesia species were detected in I. persulcatus. B. microti 'US'-type was
      identified in 10 ticks, Babesia closely related to B. divergens/B. capreoli in 2
      ticks, and Babesia closely related to B. venatorum (EU1) in 12 ticks. CONCLUSION:
      To our knowledge, this is the first detection of Babesia sensu stricto in I.
      persulcatus ticks and of B. microti in I. persulcatus in the Asian part of
      Russia.

PMID- 20800012
TI  - Efficacy of antidepressants: a re-analysis and re-interpretation of the Kirsch
      data.
AB  - Recently there has been much debate on the true usefulness of antidepressant
      therapy especially after the publication of a meta-analysis by Kirsch et al.
      (PLoS Medicine 2008, 5, e45). The aim of the current paper was to recalculate and
      re-interpret the data of that study. Effect-size and mean-score changes were
      calculated for each agent separately as well as pooled effect sizes and mean
      changes on the basis of the data reported by Kirsch et al. The weighted mean
      improvement was (depending on the method of calculation) 10.04 or 10.16 points on
      the Hamilton Depression Rating Scale (HAMD) in the drug groups, instead of 9.60,
      and thus the correct drug-placebo difference is 2.18 or 2.68 instead of 1.80.
      Kirsch et al. failed to report that that the change in HAMD score was 3.15 or
      3.47 points for venlafaxine and 3.12 or 3.22 for paroxetine, which are above the
      NICE threshold. Still the figures for fluoxetine and nefazodone are low. Thus it
      seems that the Kirsch et al.'s meta-analysis suffered from important flaws in the
      calculations; reporting of the results was selective and conclusions unjustified
      and overemphasized. Overall the results suggest that although a large percentage
      of the placebo response is due to expectancy this is not true for the active drug
      and effects are not additive. The drug effect is always present and is unrelated
      to depression severity, while this is not true for placebo.

PMID- 20800013
TI  - Eye fluke-induced cataracts in natural fish populations: is there potential for
      host manipulation?
AB  - Manipulation of host phenotype (e.g. behaviour, appearance) is suggested to be a
      common strategy to enhance transmission in trophically transmitted parasites.
      However, in many systems, evidence of manipulation comes exclusively from
      laboratory studies and its occurrence in natural host populations is poorly
      understood. Here, we examined the potential for host manipulation by Diplostomum
      eye flukes indirectly by quantifying the physiological effects of parasites on
      fish. Earlier laboratory studies have shown that Diplostomum infection
      predisposes fish to predation by birds (definitive hosts of the parasites) by
      reducing fish vision through cataract formation. However, occurrence of cataracts
      and the subsequent potential for host manipulation in natural fish populations
      has remained poorly explored. We studied the occurrence of eye fluke-induced
      cataracts from 7 common fish species (Gymnocephalus cernuus, Rutilus rutilus,
      Leuciscus leuciscus, Alburnus alburnus, Osmerus eperlanus, Coregonus lavaretus
      and Gasterosteus aculeatus) from the Bothnian Bay in the Baltic Sea. We found
      that the parasite-induced cataracts were common in fish and they also reached
      high levels which are likely to predispose fish to predation. However, we
      observed such cataracts only in species with the highest parasite abundances,
      which suggests that only certain hosts may be strongly affected by the infection.

PMID- 20800014
TI  - Is there a role for the nuclear receptor PPARgamma in neuropsychiatric diseases?
AB  - The aetiology of psychiatric diseases such as depression or schizophrenia remains
      largely unknown, even though multiple theories have been proposed. Although
      monoamine theory is the cornerstone of available pharmacological therapies,
      relapses, incomplete control of symptoms or failure in treatment occur
      frequently. From an inflammatory/immune point of view, both entities share
      several common hallmarks in their pathophysiology, e.g. neuroendocrine/immune
      alterations, structural/functional abnormalities in particular brain areas, and
      cognitive deficits, suggesting a dysregulated inflammatory-related component of
      these diseases that better explains the myriad of symptoms presented by affected
      individuals. In this review we aimed to explore the role and relevance of
      inflammatory related lipids (prostanoids) derived from arachidonic acid
      metabolism by identification of new inflammatory markers and possible
      pharmacological/dietary modulation of these compounds, with the aim of improving
      some of the symptoms developed by individuals affected with psychiatric diseases
      (a critical review of basic and clinical studies about inflammatory-related
      arachidonic acid metabolism on neuropsychiatric diseases is included). As a
      specific candidate, one of these immunoregulatory lipids, the anti-inflammatory
      prostaglandin 15d-PGJ2 and its nuclear receptor peroxisome proliferator-activated
      nuclear receptor (PPARgamma) could be used as a biological marker for psychiatric
      diseases. In addition, its pharmacological activation can be considered as a
      multi-faceted therapeutic target due to its anti-inflammatory/antioxidant/anti
      excitotoxic/pro-energetic profile, reported in some inflammatory-related
      scenarios (neurological and stress-related diseases). PPARs are activated by a
      great variety of compounds, the most relevant being the currently prescribed
      group of anti-diabetic drugs thiazolidinediones, and some cannabinoids (both
      endocannabinoids, phytocannabinoids or synthetic), as possible novel
      therapeutical strategy.

PMID- 20800015
TI  - Morphological changes and viability of Cryptosporidium parvum sporozoites after
      excystation in cell-free culture media.
AB  - Cryptosporidium parvum, belonging to the phylum Apicomplexa, is a major cause of
      waterborne gastroenteritis throughout the world. The sporozoites are thought to
      invade host enterocytes using an active process termed gliding motility. However,
      the biological and morphological changes within the sporozoites during this
      process are not fully understood. In the present study, excysted sporozoites of
      C. parvum were analysed ultrastructurally in vitro and their viability was
      evaluated using fluorescent dyes. The sporozoites excysted from oocysts changed
      morphologically from banana-shaped to rod-shaped and finally to a rounded shape,
      in culture media in 3 h. Transmission microscopy revealed that the distance
      between the apical end and the nucleus was markedly reduced, dense granules were
      present close to the rhoptry in the apical region, amylopectin granules were
      absent, and membranes of round sporozoites were less clear. A fluorescent assay
      showed that the rate of survival decreased from 89% to 56% at 0-3 h (84.3% for
      banana-shaped and 49.2% for rod-shaped sporozoites). Therefore, post-excysted
      sporozoites in vitro underwent morphological changes and a rapid loss of
      viability. This staining method is useful, inexpensive and provides an
      alternative to more costly and intensive flow cytometric assays or infectivity
      assays with host cells in vitro.

PMID- 20800016
TI  - Population dynamics of the liver fluke, Fasciola hepatica: the effect of time and
      spatial separation on the genetic diversity of fluke populations in the
      Netherlands.
AB  - An evaluation of the genetic diversity within Fasciola hepatica (liver fluke) may
      provide an insight into its potential to respond to environmental changes, such
      as anthelmintic use or climate change. In this study, we determined the
      mitochondrial DNA haplotypes of > 400 flukes from 29 individual cattle, from 2
      farms in the Netherlands, as an exemplar of fasciolosis in a European context.
      Analysis of this dataset has provided us with a measure of the genetic variation
      within infrapopulations (individual hosts) and the diversity between
      infrapopulations within a herd of cattle. Temporal sampling from one farm allowed
      for the measurement of the stability of genetic variation at a single location,
      whilst the comparison between the two farms provided information on the variation
      in relation to distance and previous anthelmintic regimes. We showed that the
      liver fluke population in this region is predominantly linked to 2 distinct
      clades. Individual infrapopulations contain a leptokurtic distribution of
      genetically diverse flukes. The haplotypes present on a farm have been shown to
      change significantly over a relatively short time-period.

PMID- 20800017
TI  - Testing temporal stability of the larval digenean community in Heleobia conexa
      (Mollusca: Cochliopidae) and its possible use as an indicator of environmental
      fluctuations.
AB  - Larval digeneans have been proposed as indicators of abundance and diversity of
      vertebrate and other hosts as well as environmental disturbances. To evaluate its
      response to environmental changes and its potential use as an indicator of
      environmental fluctuations, the temporal stability of the community of larval
      digeneans in Heleobia conexa was comparatively analysed in 4 separate years
      (1996, 1999, 2004 and 2005) in Mar Chiquita coastal lagoon (Buenos Aires
      province, Argentina). In total, 4579 specimens of H. conexa were collected and 22
      digenean species were observed. Overall prevalence presented inter-annual and
      seasonal differences. These differences correlate with seasonal changes in
      composition of the vertebrate definitive host community and with the elimination
      of the preferred habitat of H. conexa in 1999. In general, the larval digenean
      community of H. conexa showed a yearly re-establishment following the annual
      cycle of H. conexa and the presence of definitive hosts. This annual
      restructuring allowed inferences about the effects of short-term environmental
      changes in the lagoon. According to these observations, the larval digenean
      community of H. conexa could be considered as a good bio-indicator with quick
      response to environmental disturbances.

PMID- 20800018
TI  - Recent progress in nanotechnology for cancer therapy.
AB  - The application of nanotechnology significantly benefits clinical practice in
      cancer diagnosis, treatment, and management. Especially, nanotechnology offers a
      promise for the targeted delivery of drugs, genes, and proteins to tumor tissues
      and therefore alleviating the toxicity of anticancer agents in healthy tissues.
      This article reviews current nanotechnology platforms for anticancer drug
      delivery, including polymeric nanoparticles, liposomes, dendrimers, nanoshells,
      carbon nanotubes, superparamagnetic nanoparticles, and nucleic acid-based
      nanoparticles [DNA, RNA interference (RNAi), and antisense oligonucleotide (ASO)]
      as well as nanotechnologies for combination therapeutic strategies, for example,
      nanotechnologies combined with multidrug-resistance modulator, ultrasound,
      hyperthermia, or photodynamic therapy. This review raises awareness of the
      advantages and challenges for the application of these therapeutic
      nanotechnologies, in light of some recent advances in nanotechnologic drug
      delivery and cancer therapy.

PMID- 20800019
TI  - Blimp-1 protein and Hans classification on prognosis of diffuse large B-cell
      lymphoma and their interrelation.
AB  - BACKGROUND AND OBJECTIVE: Diffuse large B-cell lymphoma (DLBCL), the most common
      type of non-Hodgkin's lymphoma (NHL), is heterogeneous on molecular and clinical
      levels, therefore, its prognosis is difficult to predict. This study aimed to
      evaluate the value of Blimp-1 protein and Hans classification in predicting the
      prognosis of DLBCL and their interrelation. METHODS: The clinical records of 136
      patients with DLBCL were reviewed. The patients were followed up for 5-80 months
      (median, 39 months). Immunohistochemical staining for CD10, MUM1, Bcl-6, and
      Blimp-1 were performed on paraffin-embedded tumor tissues from the 136 patients.
      The correlations of Blimp-1 protein and Hans classification in prognosis of DLBCL
      and their interrelation were analyzed. RESULTS: Blimp-1 was detected in 38
      (30.0%) patients, and was associated with a significantly shorter overall
      survival (OS) (P = 0.030). Using the Hans classification based upon the
      expression of CD10, Bcl-6, and MUM1, 54 patients had germinal center B-cell (GCB)
      phenotype and 82 had non-GCB phenotype. The 5-year OS rate was 75% in the GCB
      group and 52% in the non-GCB group (P = 0.020). The positive rate of Blimp-1 was
      22.2% in the GCB group and 31.7% in the non-GCB group (P = 0.329). The Cox
      regression multivariate analysis showed that international prognosis index (IPI)
      and Hans classification had independent prognostic significance, whereas Blimp-1
      was not an independent prognostic factor. CONCLUSIONS: The patients with GCB
      subtype of DLBCL had better prognosis than the non-GCB subtype. High level of
      Blimp-1 expression in the patients with DLBCL implies a shorter survival, but it
      is not associated with Hans classification.

PMID- 20800020
TI  - The results and prognosis of different treatment modalities for solitary
      metastatic lung tumor from nasopharyngeal carcinoma: a retrospective study of 105
      cases.
AB  - BACKGROUND AND OBJECTIVE: Nasopharyngeal carcinoma (NPC) is known for its
      propensity for distant metastases. Lung metastasis is one of the most important
      causes of death for patients with NPC. Solitary metastatic lung tumor from NPC is
      a distinctive group associated with a better survival. This study was to find a
      more effective treatment modality and prognostic factors for the group. METHODS:
      Clinical data of 105 cases of solitary metastatic lung tumor from NPC were
      retrospectively analyzed. Survival rate was calculated by the Kaplan-Meier
      method. The difference of survival between the patients treated by different
      modalities was evaluated by the log-rank test. The Cox univariate and
      multivariate analyses of gender, age, pathologic type, stage, adjuvant
      chemotherapy, evaluation of treatment for NPC, disease-free interval, size of
      metastatic tumor, pulmonary hilar and/or mediastinal lymph node metastasis,
      treatment modalities, recurrent distant metastases and/or relapse of NPC were
      conducted. RESULTS: The local control rate was 53.8% in chemotherapy group, 88.0%
      in radiotherapy +/- chemotherapy group, and 96.4% in operation +/- chemotherapy
      group (P < 0.01). The most promising progression-free survival (PFS) and overall
      survival (OS) were obtained with operation +/- chemotherapy and followed by
      radiotherapy +/- chemotherapy. Both of them showed much better efficacy than
      chemotherapy (P < 0.001). The Cox multivariate analysis showed that recurrent
      distant metastases and/or relapse of NPC affected the survival (OR = 2.087, 95%
      CI = 1.277-3.410, P = 0.003). The T stage of NPC, size of metastatic tumor, hilar
      and/or mediastinal lymph node metastasis, and the treatment modality were
      independent prognostic factors. CONCLUSIONS: Operation +/- chemotherapy and
      radiotherapy +/- chemotherapy are better treatment of solitary metastatic lung
      tumor from NPC, which could improve the local control and prolong the PFS and OS.
      Chemotherapy is recommended for patients with higher T stage of NPC, size of
      metastatic tumor >= 3 cm, pulmonary hilar and/or mediastinal lymph node
      metastasis.

PMID- 20800021
TI  - Lentiviral vector-mediated doxycycline-inducible iASPP gene targeted RNA
      interference in hepatocellular carcinoma.
AB  - BACKGROUND AND OBJECTIVE: iASPP, an inhibitory member of the apoptosis
      stimulating proteins of p53 (ASPP) family, has been found to be up-regulated in
      various human tumor types. This study was to construct an efficient doxycycline
      regulated, lentiviral vector-mediated knockdown system for iASPP that will allow
      for inducible down-regulation of iASPP gene expression and preliminary functional
      analysis. METHODS: A pair of complementary oligos with hairpin structures
      targeting the iASPP gene and a negative control were synthesized, then ligated
      with pLVTHM vector and sequenced. The fragment containing the shRNA cassette was
      cloned to pLVCT-tTR-KRAB plasmid. The recombinant vectors were co-transfected
      with viral packaging mix into 293T cells, and viral supernatant was harvested to
      determine the titer. After treatment with or without doxycycline, HepG2 cells
      infected with virus were harvested and the expression of iASPP was detected by
      reverse transcription-polymerase chain reaction (RT-PCR) and Western blot
      analysis. Its effects on tumor growth were characterized using MTS assay, soft
      agar colony formation, and flow cytometry analysis. RESULTS: The lentiviral
      vector expressing shRNA that targets to the oncogene iASPP was constructed
      successfully. HepG2 infected with the lentivirus expressing shRNA against iASPP
      inhibited the expression of iASPP in the presence of doxycycline, which resulted
      in the repression of tumor cell proliferation and anchorage-independent growth
      potential. CONCLUSIONS: The lentiviral vector-mediated tet-on system demonstrates
      efficient and inducible knockdown of iASPP in hepatocellular carcinoma cells.
      iASPP gene may be involved in tumorigenesis and progression of human tumors.

PMID- 20800022
TI  - Preliminary efficacy of CyberKnife radiosurgery for locally advanced pancreatic
      cancer.
AB  - BACKGROUND AND OBJECTIVE: CybeKnife is a newly developed technology in the field
      of stereotactic radiosurgery/radiotherapy (SRS/SRT). Compared with conventional
      SRS/SRT, there are many advantages for CyberKnife in terms of treating tumors
      that move with respiration, being real-time image-guidance, frameless, high
      accurateness, and so on. Recently, it has been used to treat different types of
      malignant carcinoma including intracranial and caudomedial tumors. This study was
      designed to evaluate the short-term efficacy and toxicity of the CyberKnife
      radiotherapy for locally advanced pancreatic cancer. METHODS: A total of 20
      patients with locally advanced (stage II-III) pancreatic cancer treated with
      CyberKnife were recruited between April 2009 and December 2009. Of 20 patients,
      13 were with cancer located at the pancreatic head and 7 were located at the
      pancreatic body and tail. The planning target volume (PTV) was defined as gross
      tumor volume (GTV) plus 2-3 mm, and more than 95% PTV should be covered by 75%
      isodose surface. The median of PTV was 47 cm3 (26-64 cm3). The median total
      prescription dose was 40 Gy (32-55 Gy) at 3-6 fractions. During treatment
      delivery, X-Sight Spine Tracking System was used in 5 patients to track movement
      of the tumor. Other 15 patients were implanted fiducials in the tumors to track
      movement of the tumor and patient breathing patterns. RESULTS: The median follow
      up time was 7 months (3-11 months). All patients had finished the treatment and
      19 were alive by the last follow-up. Slight fatigue was the most common complain.
      Evaluated by CT scan, 6 were complete response, 9 were partial response, 3 were
      stable disease, and 1 was progression; 1 was dead. There were 6 patients with
      grade I granulocytopenia, 7 with grade I nausea, and 5 with grade II vomiting.
      CONCLUSIONS: The CyberKnife radiosurgery for the locally advanced pancreatic
      cancer shows a high rate of local control and minimal toxicity. Long-term follow
      up is necessary to evaluate the survival and late toxicity.

PMID- 20800023
TI  - 5-Fluorouracil upregulates the activity of Wnt signaling pathway in CD133
      positive colon cancer stem-like cells.
AB  - BACKGROUND AND OBJECTIVE: CD133-positive colon cancer stem like cells (CSLCs) are
      resistant to the conventional cytotoxic drug 5-fluorouracil (5-FU). Wnt signaling
      pathway plays important roles in colon cancer carcinogenesis and metastasis, and
      regulates the self-renewal capacity of CSLCs. In the present study, we explored
      the impact of 5-FU on Wnt signaling pathway of CD133-positive colon CSLCs, and
      the relation between Wnt signaling pathway and drug resistance of CD133-positive
      colon CSLCs. METHODS: Magnetic activation cell separation was used to collect
      CD133-positive cells from colon cancer cell line DLD1, which was transfected with
      luciferase reporter for Wnt signaling activity. The activity of Wnt signaling
      pathway was compared between CD133-positive and CD133-negative cells. After the
      treatment with 1 MUg/mL of 5-FU, the cell proliferation rates of DLD1 cells,
      CD133-positive cells, and CD133-negative cells were compared. After the treatment
      with 1 MUg/mL and 10 MUg/mL of 5-FU for 48 h, Wnt activity was compared between
      CD133-positive and CD133-negative cells. The expression of CD133 and cell
      apoptosis of CD133-positive cells was detected after exposure to 50 ng/mL of
      dickkopf (DKK)-1, a Wnt pathway inhibitor. RESULTS: After the treatment with 5
      FU, the cell proliferation rate of CD133-positive cells was higher than that of
      CD133-negative cells and the sensitivity of CD133-positive cells to 5-FU
      decreased. Wnt activity was higher in CD133-positive cells than in CD133-negative
      cells [(46.3 +/- 0.3)% vs. (33.9 +/- 2.7)%, P = 0.009]. After the treatment with
      1 MUg/mL and 10 MUg/mL of 5-FU, Wnt activity of CD133-positive cells was (90.1 +/
      10.0)% (P = 0.012) and (52.9 +/- 2.5)% (P = 0.047), respectively, whereas that
      of CD133-negative cells was (35.5 +/- 3.3)% (P = 0.434) and (26.5 +/- 0.4)% (P =
      0.046), respectively. CD133 expression in CD133-positive cells decreased from
      (87.2 +/- 5.3)% to (60.6 +/- 3.1)% (P = 0.022) after treatment with DKK-1,
      whereas the cell apoptosis rate increased from (11.8 +/- 0.2)% to (28.3 +/- 0.6)%
      (P = 0.013). CONCLUSIONS: Wnt activity is higher in CD133-positive DLD1 cells
      than in CD133-negative DLD1 cells. 5-FU can upregulate Wnt activity of CD133
      positive colon CSLCs. Blocking Wnt activity may reverse drug sensitivity of CD133
      positive cells to 5-FU.

PMID- 20800024
TI  - Effects of small interfering RNA targeting heparanase-1 combined with heparin on
      invasiveness of mouse hepatocellular carcinoma cell lines.
AB  - BACKGROUND AND OBJECTIVE: Heparanase-1 (HPA-1) can promote angiogenesis and
      metastasis of malignant tumors and plays an important role in the genesis and
      development of tumors. This study was to explore the effects of specific small
      interfering RNA (siRNA) targeting HPA-1 combined with heparin on invasiveness of
      mouse hepatocellular carcinoma cells. METHODS: The expression of HPA-1 in Hca-F,
      Hca-P, and Hepa1-6 cells, which have high, low, and no metastatic potential,
      respectively, was analyzed by reverse transcription-polymerase chain reaction (RT
      PCR), Western blot analysis and enzyme-linked immunosorbent assay (ELISA). After
      transfection with two specific siRNAs targeting HPA-1, siRNA-1 and siRNA-2, and
      treatment with heparin, invasiveness of Hca-F cells was observed by Matrigel
      invasion assay. RESULTS: HPA-1 was negative in Hepa1-6 cells while positive in
      both Hca-F and Hca-P cells. The expression levels of both HPA-1 mRNA and protein
      were obviously higher in Hca-F cells than in Hca-P cells. HPA-1 proteins could be
      secreted into culture supernatant of Hca-F and Hca-P cells, and the amount of
      secreted HPA-1 detected by Western blot analysis was larger in Hca-F cells than
      in Hca-P cells (1.34 +/- 0.02 vs. 0.60 +/- 0.01, P < 0.001), which was consistent
      with the results of ELISA. Both siRNA-1 and siRNA-2 downregulated the expression
      of HPA-1 and the siRNA-2 did more efficiently. The number of invasive Hca-F cells
      treated with siRNA-2 or heparin alone was larger than that of Hca-F cells treated
      with combination of them (9 +/- 1 vs. 4 +/- 1, P = 0.013; 15 +/- 2 vs. 4 +/- 1, P
      = 0.008), but smaller than that of untreated Hca-F cells (9 +/- 1 vs. 22 +/- 2, P
      = 0.006; 15 +/- 2 vs. 22 +/- 2, P = 0.026). CONCLUSION: The combined application
      of specific siRNA targeting HPA-1 and heparin is more effective in inhibiting the
      invasiveness of mouse hepatoma cells.

PMID- 20800025
TI  - Damage of nasal mucociliary movement after intensity-modulated radiation therapy
      of nasopharyngeal carcinoma.
AB  - BACKGROUND AND OBJECTIVE: Radiation usually results in paranasal sinusitis in
      patients with nasopharyngeal carcinoma (NPC), which influences patients' quality
      of life. This study aimed to determine the relationships between dose
      distribution in the nasal cavity and nasal mucous injury in patients with NPC
      treated by intensity-modulated radiation therapy (IMRT), and to find the
      tolerable radiation dose for the nasal mucous. METHODS: Sixty-six patients with
      NPC treated by IMRT between October 2006 and November 2008 were enrolled. The
      irradiation dose in the nasal cavity was determined by the computer with the IMRT
      work platform. Mucociliary transport rate (MTR) was detected by modified
      saccharine test before IMRT, at the end of IMRT, and at 3, 6, and 12 months after
      IMRT. RESULTS: The data were available for 129 nasal cavities. The cavities
      receiving a mean dose below or equal to 37 Gy showed substantial preservation of
      nasal mucous after IMRT. The MRT decreased to (62.82 +/- 38.59)%, (56.78 +/-
      37.79)%, (64.05 +/- 39.37)%, and (71.13 +/- 39.55)% of pre-IMRT value at 4 time
      points after IMRT, with significant differences among the data (P < 0.05). In
      contrast, when the cavities received a mean dose higher than 37 Gy, no
      significant differences in MTR among the time points were observed. At 3 months
      after IMRT, the MTR was the lowest (38.27% of pre-RT value). CONCLUSIONS: A mean
      radiation dose of <= 37 Gy for the nasal cavity is an optimal dose to protect the
      nasal cavity function.

PMID- 20800026
TI  - Percutaneous ultrasound-guided thermal ablation for liver tumor with artificial
      pleural effusion or ascites.
AB  - BACKGROUND AND OBJECTIVE: Percutaneous ultrasound-guided thermal ablation is one
      of the major treatment methods for liver cancer. Tumor location close to the
      diaphragm or gastrointestinal tract was regarded as the treatment
      contraindication before due to poor visibility of the tumor or increased risk of
      thermal injury to the adjacent organs. This study used artificial pleural
      effusion or ascites to extend the indications of thermal ablation for liver
      cancer. METHODS: Artificial pleural effusion (20 cases) or ascites (36 cases) was
      performed in 56 difficult cases of percutaneous thermal ablation for liver
      tumors. The technical success rates, the rate of approaching the procedure goal,
      complications, and local treatment response were assessed. RESULTS: The technical
      success rates were 95% (19/20) for artificial pleural effusion and 100% (36/36)
      for artificial ascites, the achieve purpose rates were 100% (19/19) and 91.7%
      (33/36), the complete ablation rates were 84.2% (16/19) and 93.9% (31/33),
      respectively. Coughing, transient hematuria, and subcutaneous effusion were
      observed in 3 patients after the procedure of artificial pleural effusion, and
      hydrothorax in the right chest occurred in 1 patient during the artificial
      ascites process. CONCLUSIONS: Thermal ablation with the use of artificial pleural
      effusion or ascites is a safe and effective treatment for liver tumors, and the
      technique can widen the indications of thermal ablation for liver tumors.

PMID- 20800027
TI  - Percutaneous radiofrequency ablation approach through the spleen: initial case
      report for pancreatic tail gastrinoma.
AB  - Gastrinoma has a low incidence, and the pancreas-originated gastrinoma is rare.
      Pancreatic gastrinoma patients with liver metastases have poor prognosis and
      short survival. Local treatment to reduce the tumor burden helps to improve
      symptoms and slows down tumor progression for patients with unresectable tumors.
      We report a case of pancreatic tail gastrinoma with unresectable liver
      metastases. The patient received a comprehensive minimally invasive
      interventional treatment, that is, chemoembolization and radiofrequency ablation
      for liver metastases, and percutaneous transplenic radiofrequency ablation
      combined with radioactive 125I seed implantation for pancreatic tail gastrinoma.
      The patient was followed up for more than 20 months, and showed no clear evidence
      of tumor recurrence. We explored the safety and feasibility of percutaneous
      transplenic radiofrequency ablation for unresectable pancreatic tail gastrinoma.
      This transplenic approach allow more indications for minimally invasive therapy
      and provides a new treatment option not only for patients with unresectable
      pancreatic tail tumor but also for patients refusing surgery.

PMID- 20800028
TI  - [Comments on article "A new technique to perform percutaneous nephrolithotripsy
      in "total dorsal decubitus position""].

PMID- 20800029
TI  - [Beyond the photodynamic diagnosis: Searching for excellence in the diagnosis of
      non-muscle-invasive bladder cancer].
AB  - Cystoscopy is gold-standard method in non muscule invasive bladder cancer
      diagnosis. In the cistoscopic exploration 30% of tumors could be overlooked: it
      is due to a flat forms, little size tumours or difficult visualization.
      Photodynamic diagnosis reduces overlooked tumours rate, and has improved
      diagnosis on flat forms, with the consequence of increasing lap time to
      recurrence and decreasing the number of iterative cistoscopy; nevertheless the
      false positive rate is high. In the last years developed new optical devices who
      try to improve alone or associated diagnostic sensibility in cistoscopy without
      reduction of specificity. Among new devices we must emphasize some like Narrow
      Band Imaging, Optical Coherence Tomography or Laser Confocal Endomicroscopy.

PMID- 20800030
TI  - [Reference values of prostate specific antigen (PSA) in 63926 workers without
      prostatic symptoms who participated in prostate screening cancer developed by the
      Ibermutuamur Prevention Society in 2006].
AB  - OBJECTIVE: To determine the values of PSA in Spanish workers without history of
      prostate problems and compare them with other geographical latitudes. METHODS:
      Observational, retrospective, multicenter and population-based study, conducted
      between January 1 and December 31, 2006. A total of 65303 workers participated in
      the Programme of prostate cancer screening conducted by the Ibermutuamur
      Prevention Society in different Spanish regions. Of these, were selected for this
      report, 63926: 149 were excluded by personal history of prostate problems and
      1328 for being over 64 years. PSA determinations were performed using the Abbott
      test. Were specified PSA values for each age and for the following age ranges:
      younger than 40 years, 40-49 years, 50-59 years and 60-64 years. Also calculated
      the mean PSA values by Autonomous Communities. The data were expressed as mean
      (+/-SD), confidence intervals 95%, standard error of the mean (SEM) and in the
      percentiles 5, 25, 50, 75 and 95. The results obtained were compared with those
      in other areas of the world. All data were analysed using the statistical
      software GraphPad Quick Calcs. RESULTS: Mean PSA value: for all cases was 1.06
      ng/ml (95% CI: +/-1,18) and age groups: under 40 years, 0.67 ng/ml (95% CI: +/
      0.49), 40-49 years, 0, 77 ng/ml (95% CI: +/-0.66), 50-59 years, 1.11 ng/ml (95%
      CI: +/-1.22) and 60-64 years, 1.57 ng/ml (95% CI: +/-1.72). Depending on the age
      ranged between 0.67 ng/ml under age 40 and 1.70 in the 64 years. According to
      region, the lowest value was recorded in the Pais Vasco with 0.98 ng/ml (95% CI:
      1.02) and higher in Asturias with 1.28 ng/ml (95% CI: 1.32). Percentile value
      PSA: the upper normal limit (95th percentile) was 1.40 ng/ml in those younger
      than 40 years, 1.70 ng/ml in 40-49 years, 3.30 ng/ml in 50-59 years and 5.18
      ng/ml in the group 60-64 years. CONCLUSIONS: PSA values collected in this study
      may serve as a reference for the Spanish working population, using the range
      described for decades, or even better, those relating to each age.

PMID- 20800031
TI  - [Erectile dysfunction in patients with prostate cancer who have undergone
      surgery: Systematic review of literature].
AB  - OBJECTIVE: To assess erectile dysfunction in patients with prostate cancer
      undergoing surgery by radical prostatectomy, laparoscopic prostatectomy or
      robotic prostatectomy. MATERIAL AND METHODS: Systematic Review of literature
      based on a search strategy (2000-10) in MedLine, Embase, Cochrane Library, CRD,
      ECRI, and Hayes. Mesh terms used were Prostatectomy, "Prostatic Neoplasm,
      Transuretral Resection Prostate, Impotence and as free terms erectile dysfunction
      and prostatectomy. Studies included patients with prostate cancer underwent by
      prostatectomy radical with open surgery (retropubic), laparoscopic or robotic
      surgery. RESULTS: Ten observational studies with moderate quality and 29 case
      series with low quality were selected. Observational studies showed lower
      percentages of erectile dysfunction after intervention in the patients underwent
      robotic surgery (3-51%). Radical surgery (36-91%) and laparoscopic surgery showed
      higher values of impotence. In the studies that compared surgery versus
      radiotherapy, the results were better for radiotherapy (3-72% erectile
      dysfunction). In the case series, lower percentages of erectile dysfunction were
      shown in patients underwent to robotic surgery (22%), the following was for
      laparoscopic surgery (40%) and open radical prostatectomy (41.4%). CONCLUSIONS:
      This result should be considered with caution because of the low methodological
      quality of the studies included. However, the different surgical techniques
      assessed showed similar effects in the two types of studies included and we found
      that robotic surgery presented lower percentages of sexual impotence.

PMID- 20800032
TI  - [CAVIPRES questionnaire as a measurement of quality of life in patients with
      prostate cancer in Spain: Daily clinical practice application].
AB  - INTRODUCTION: Prostate cancer (PC) states as the most frequent tumor in elderly
      patients. Although no direct involvement in death-related, PC entails an
      important lost in patient's quality of life. There are several questionnaires
      adapted to Spanish in order to measure the health-related quality of life (HRQoL)
      in PC patients. OBJECTIVES: To describe the content and feasibility of the
      Spanish CAVIPRES questionnaire both in its short version to the clinical daily
      practice and also in the extended version to be used in the investigational
      protocols. MATERIALS AND METHODS: A detailed review of the different quality of
      life-related aspects of PC patients gathered in the questionnaire and a cross
      comparison with other adapted HRQoL available is been performed. RESULTS: The
      HRQoL CAVIPRES questionnaire gathers information regarding social and partner
      support, psychological conditions of the patients, and also life expectancies
      against disease outcome together with classical symptomatic parameters as other
      available and adapted questionnaires. CONCLUSION: The CAVIPRES questionnaire in
      its short version is an adequate, feasible, valid, reliable and sensitive to
      change in the measurement of HRQoL in PC patients. The extended version is valid
      to be used in clinical research of PC patients. Both versions have been donated
      by Abbott to the Spanish Association of Urology (AEU) and are available at AEU
      web site (www.eau.es).

PMID- 20800033
TI  - [Detection of renin in chromophobe renal cell carcinomas].
AB  - AIM: To evaluate frequency of renin detection in chromophobe renal cell
      carcinoma, and if this expression was associated to systemic high blood pressure.
      MATERIAL AND METHODS: A descriptive retrospective study. All the cases with
      confirmed diagnosis of chromophobe carcinoma and resected between 1990 and 2004
      were included in our study: 31 cases from 31 patients. Immunohistochemistry was
      carried out on sections from the paraffin-embedded tissue using a monoclonal
      antiserum. Patient blood pressure before and after neoplasm resection was
      registered from clinical histories. We compared frequencies of hypertension in
      cases with and without expression of renin (Fisher's text or chi(2) as
      appropriate) and evolution of HTA after tumour resection. RESULTS: We found that
      10 of 31 tumors (32.3%) contained immunoreactivity for renin; this staining was
      diffuse in 6 cases and focal in the other 4. Systemic hypertension was detected
      in 6 of 10 (60.0%) patients with renin expression and in 6 of 21 (28.6%) patients
      without renin immunolabeling (p=0.13). After tumor resection none patient with
      renin expression and high blood pressure showed remission of the hypertension.
      CONCLUSION: Renin is frequently expressed in chromophobe renal cell carcinoma,
      but this renin appears clinically inactive. More studies will be necessary to
      know implications of this feature on clinical presentation, diagnosis or
      pathogenesis.

PMID- 20800034
TI  - [Evaluation of self-esteem in males with erectile dysfunction treated with
      viagra. Analysis of a Spanish patients group selected from a multicenter,
      international study].
AB  - INTRODUCTION AND OBJECTIVES: Erectile dysfunction (ED) leads to psychological
      disturbances, especially anxiety and loss of self-esteem. We try to understand
      the emotional changes, based on self-esteem and relationships in a group of
      Spanish men with ED after sildenafil treatment, with the use of the the SEAR
      questionnaire (Self-Esteem And Relationship). MATERIALS AND METHODS: The patients
      recruited in Spain, where selected from an international, multicenter,
      randomized, parallel-group, double-blind, placebo-controlled, sildenafil study
      designed to assess self-esteem and relationships in men with ED. We compared the
      changes in the different domains of the SEAR questionnaire (Self-steem, sexual
      activity, self-confidence and general relationships) that was administered before
      and after treatment; the different domains of the IIEF was evaluated as well. We
      also calculated the correlation between changes in self-esteem domain of the SEAR
      questionnaire. The statistical study was based on an analysis of covariance of
      change in scores and a correlation analysis. RESULTS: The Spanish group of
      researchers included 119 patients. The erectile function domain score showed
      significantly greater improvement for the group of sildenafil. The difference in
      change in total mean score of the SEAR after treatment was 16.9 (95% CI 8.9,
      24.8) for sildenafil over placebo (p=0.0001), with a significantly higher score
      improvement in all the domains of the SEAR for Sildenafil. There was a
      significant correlation between the changes in the domain of self-esteem of the
      SEAR and the IIEF erectile function domain for both treatment groups.
      CONCLUSIONS: Emotional improvement was confirmed in patients treated with
      sildenafil based on improved self-esteem, self-confidence and relationships.
      Changes in the IIEF erectile function domain correlate with the SEAR self-esteem
      domain.

PMID- 20800035
TI  - [Impact of topic administration of nitric oxide donor gel in the clitoridian
      blood flow, assessed by Doppler ultra-sound].
AB  - OBJECTIVE: This study aims to evaluate of the impact of NO molecules in Pluronic
      F-127 gel, applied topically in the clitoris, on the clitoridian blood flow of
      healthy volunteer women, using the Doppler ultra-sound. METHOD: A total of 20
      healthy women over 18 years old and sexually active with no sexual hormones
      alteration were enrolled. The Doppler ultra-sound procedure was performed on the
      artery of the clitoris in patients without the NO donor gel, and then after
      fifteen minutes of its application the same procedure was done again, to compare
      the values. RESULTS: The hemodynamic results showed, that this formulation was
      responsible for the increase of the systolic and diastolic speeds in about 2,5
      times after 15 min of the administration of the gel. The initial resistance index
      was increased in 1.2 due to the local venous congestion in only 15 min after the
      administration of gel. Indicating that this product can be used to promote the
      dilatation of the artery of the clitoris to treat women with sexual dysfunction.
      CONCLUSION: The use of topic hidrogel as a donor drug in the clitoris of women
      resulting in a local vasodilatation, without systemic effects. These findings
      suggest that this preparation may be useful in the management of selected cases
      of female sexual dysfunction.

PMID- 20800036
TI  - [Holmium laser enucleation of the prostate. Experience in Hospital Germans Trias
      i Pujol].
AB  - OBJECTIVES: Evaluate the introduction of the enucleation with Holmium laser in
      our center, including the surgeon's learning curve by the analysis of the
      patients. MATERIALS AND METHODS: 150 procedures have been analyzed in a
      retrospective manner with an average follow-up of 11 months. Qmax, IPSS and Qol
      have been determined before surgery, at 6 months and 12 months, realizing their
      statistic analysis. PSA was measured before surgery and after 3 months.
      Complications, surgical time and hospital stay have been analyzed. RESULTS:
      Average patient age was 72, 4 years. Average prostatic size was of 71,3 gr (18
      150). Average hospital stay was of 22 h. Qmax before surgery, 6 months, 12 months
      was of 7,53 ml/s, 23,24 ml/s and 21,62 ml/s being statistically significant
      (p<0,01). Transfusion rate was of 1,3% and urethral stenosis rate of 4%. IPSS
      improvement at 6 and 12 months was statistically significant as well (p<0, 01).
      CONCLUSIONS: Enucleation with Holmium laser is a safe and effective technique
      with lower complication rate than TURP, included during the learning curve.

PMID- 20800037
TI  - [Influence of donor age on graft survival].
AB  - INTRODUCTION: In 2007 in Spain 43% of donors were older than 60 years. This
      produces a worse graft quality and probably a worse survival. OBJECTIVE: Our
      objective is to analyze the influence of donor age on graft survival. MATERIAL
      AND METHODS: We analyze retrospectively 216 renal consecutive transplants
      realized between 2000 and 2008. A univaried and multivaried study (Cox
      regression) was performed and Kaplan-Meyer test with log rank for graft survival.
      RESULTS: Follow-up mean of 40 months (+/-33,4 SD). The univaried analysis of
      graft survival showed that donor age had a significative influence on graft
      survival. (OR=1,03; 95% CI 1,01-1,05) (p: 0,009). Studying the relation between
      donor and recipient age we find an inverse correlation (Pearson's Correlation:
      0,55. p<0,0001), but there are significative differences after the adjustment for
      recipient age. (OR: 1,02; 95% CI 1,01-1,04) (p: 0,04). Optimal cut-point value
      determined by the ROC analysis was 60 years. The graft survival of donors over 60
      years is 79% (95% CI; 74-84%) and 71% (95% CI; 65-77%) at 3 and 5 years in
      contrast with 94% (95% CI; 94-96%) and 90% (95% CI; 88-92 in donors under 60. (p:
      0,002). The multivaried study of the influential factors on graft survival
      reveals that donor age dichotomized in older or younger than 60, the presence of
      a surgical immediate reintervention and a delayed graft function were independent
      influence factors. CONCLUSIONS: Donor age over 60 years has a negative and
      independent prognostic influence on graft survival.

PMID- 20800038
TI  - [New techniques to perform percutaneous nephrolithotripsy total dorsal
      decubitus].
AB  - INTRODUCTION: Based on the knowledge on percutaneous surgeries performed by
      Valdivia-Uria technique, we developed changes which set a new technique to
      perform percutaneous nephrolithotripsy. MATERIAL AND METHODS: A retrospective
      study encompassing 1775 procedures was performed from 1996 to 2009, including all
      the patients who had undergone percutaneous nephrolithotripsy to treat urinary
      lithiasis. Patients were in total dorsal decubitus position, and it was performed
      a puncture in the posterior axillary line, dilation and placement of the Amplatz
      sheath in parallel position to the radio transparent table or slightly inclined
      downward. RESULTS: The median operating time was 55 min and a complete clearance
      of the stones was achieved in 81.8% of the cases. In 12% of the cases the
      concurrent removal of the renal and ureteral lithiasis was performed. CONCLUSION:
      This technique facilitates simultaneous ureteroscopy and nephroscopy without the
      need of repositioning the patient, and it is also a good option for percutaneous
      access.

PMID- 20800039
TI  - [Primitive neuroectodermical tumour of the kidney: Case report].

PMID- 20800040
TI  - [Sclerosing sertoli cell tumor. An unfrequent type of testicular neoplasm].

PMID- 20800041
TI  - [Giant fibroepithelial polyp of the ureter: treatment with ureteral resection and
      intestinal substitution].

PMID- 20800042
TI  - [Bladder carcinosarcoma. Two case reports and a literature review].

PMID- 20800043
TI  - [High grade dedifferentiated liposarcoma. Case report and review of the
      literature].

PMID- 20800044
TI  - [Post-renal transplantation intermittent anuria secondary to calcified granuloma
      of the neomeatus].

PMID- 20800051
TI  - Application of new semisynthetic aequorins with long half-decay time of
      luminescence to G-protein-coupled receptor assay.
AB  - Aequorin is a Ca(2+)-binding photoprotein and consists of an apoprotein
      (apoaequorin) and a 2-peroxide of coelenterazine. Eight new coelenterazine
      analogues modified at the C2-position were synthesized and incorporated into
      recombinant apoaequorin with O(2) to yield different semisynthetic aequorins. The
      luminescence properties and the sensitivity to Ca(2+) of these semisynthetic
      aequorins were characterized. Two semisynthetic aequorins, namely me- and cf3
      aequorin, showed a slow decay of the luminescence pattern with less sensitivity
      to Ca(2+) and were useful for the cell-based G-protein-coupled receptor (GPCR)
      reporter assays.

PMID- 20800052
TI  - Biosensor-based fragment screening using FastStep injections.
AB  - We have developed a novel analyte injection method for the SensiQ Pioneer surface
      plasmon resonance-based biosensor referred to as "FastStep." By merging buffer
      and sample streams immediately prior to the reaction flow cells, the instrument
      is capable of automatically generating a two- or threefold dilution series (of
      seven or five concentrations, respectively) from a single analyte sample. Using
      sucrose injections, we demonstrate that the production of each concentration
      within the step gradient is highly reproducible. For kinetic studies, we
      developed analysis software that utilizes the sucrose responses to automatically
      define the concentration of analyte at any point during the association phase. To
      validate this new approach, we compared the results of standard and FastStep
      injections for ADP binding to a target kinase and a panel of compounds binding to
      carbonic anhydrase II. Finally, we illustrate how FastStep can be used in a
      primary screening mode to obtain a full concentration series of each compound in
      a fragment library.

PMID- 20800053
TI  - The interaction of azurin and C-terminal domain of p53 is mediated by nucleic
      acids.
AB  - Azurin is bacterial protein, which was been reported to promote cancer cell death
      in vitro. The interaction of azurin and p53 is important for the cytotoxic effect
      of azurin towards cancer cells. In this study, it was found that nucleic acids
      mediated the interaction of azurin and the C-terminal domain of p53 (residues 352
      393). The results provide novel insight into the interaction, and raising the
      possibility that the allosteric regulation of C-terminus of p53 by nucleic acids
      play an important role in the interaction of p53 with azurin. Meanwhile an
      elongated expressed product of azurin was cloned and purified, which was found to
      have stronger interaction with C-terminal domain of p53. Cytotoxicity studies
      showed that the cytotoxic effect of this elongated expressed product of azurin
      was stronger than wild-type azurin. The difference found in the cytotoxic effect
      of azurin with various sequence may provide valuable insight for finding more
      effective anticancer peptides.

PMID- 20800055
TI  - Mitigation and detection of spurious potassium and sodium results.
AB  - Spurious laboratory results are results that are analytically correct but do not
      accurately reflect the in vivo plasma analyte concentrations. Spurious
      electrolyte results often lead to unnecessary testing or injudicious treatment
      and have an adverse effect on patient outcome. In this review we discuss the
      preanalytical and analytical variables that lead to spurious sodium and potassium
      results. We describe ways to detect them both in the laboratory and in clinical
      practice and suggest how to prevent them.

PMID- 20800054
TI  - Kisspeptins: bridging energy homeostasis and reproduction.
AB  - Body energy reserves and metabolic state are relevant modifiers of puberty onset
      and fertility; forms of metabolic stress ranging from persistent energy
      insufficiency to morbid obesity are frequently linked to reproductive disorders.
      The mechanisms for such a close connection between energy balance and
      reproduction have been the subject of considerable attention; however, our
      understanding of the neurobiological basis for this phenomenon is still
      incomplete. In mid 1990s, the adipose-hormone, leptin, was proven as an essential
      signal for transmitting metabolic information onto the centers governing puberty
      and reproduction; yet, the ultimate mode of action of leptin on GnRH neurons has
      remained contentious for years. More recently, kisspeptins, a family of
      neuropeptides encoded by the Kiss1 gene, have emerged as conduits for the
      metabolic regulation of reproduction and putative effectors of leptin actions on
      GnRH neurons. This review recapitulates the experimental evidence obtained to
      date, mostly in laboratory rodents, supporting the function of kisspeptins in
      bridging energy balance and reproduction, with special emphasis on recent
      developments in this field, such as the recognition of mTOR (mammalian target of
      rapamycin) and Crtc1 (Creb1-regulated transcription coactivator-1) as putative
      mediators for leptin regulation of Kiss1 expression, as well as the
      identification of other potential metabolic modulators of kisspeptin signaling,
      such as ghrelin, neuropeptide Y (NPY) and melanin-concentrating hormone (MCH).

PMID- 20800056
TI  - Mutations in APOA-I and ABCA1 in Norwegians with low levels of HDL cholesterol.
AB  - BACKGROUND: Epidemiological studies have shown that low levels of plasma high
      density lipoprotein (HDL) cholesterol are associated with increased risk of
      ischemic heart disease (IHD), but it appears that genetic forms of low HDL
      cholesterol levels, as opposed to lifestyle-induced low levels of HDL
      cholesterol, do not result in increased risk of IHD. Therefore, the etiology of
      reduced levels of plasma HDL cholesterol may represent a factor that should be
      considered in risk stratification with respect to primary prevention. Genes
      encoding proteins involved in HDL metabolism, such as the ATP-binding cassette
      transporter A1 (ABCA1) and apolipoprotein (apo) A-I genes, are candidate genes
      for harboring mutations that lead to low HDL cholesterol levels. METHODS: The
      ABCA1 and apoA-I genes in 56 Norwegian patients, with a mean HDL cholesterol
      level of 0.53 (+/-0.15) mmol/l, were subjected to DNA sequencing. RESULTS:
      Several mutations were identified in the ABCA1 gene, and two mutations were
      identified in the apoA-I gene. A total of 18 patients (32%) were carriers of
      mutations considered to be pathogenic. Their mean HDL cholesterol level was 0.45
      (+/-0.15) mmol/l compared to 0.57 (+/-0.14) mmol/l in noncarriers (p<0.005).
      CONCLUSION: Mutations in the genes encoding ABCA1 and apoA-I are common in
      Norwegians, with a markedly decreased HDL cholesterol level.

PMID- 20800057
TI  - Synergistic effects of the MTHFR C677T and A1298C polymorphisms on the increased
      risk of micro- and macro-albuminuria and progression of diabetic nephropathy
      among Iranians with type 2 diabetes mellitus.
AB  - OBJECTIVES: To find whether polymorphisms of methylenetetrahydrofolate reductase
      (MTHFR) C677T and A1298C are risk factors for diabetic nephropathy (DN) among
      type 2 diabetes mellitus (T2DM) patients from Western Iran. DESIGN AND METHODS:
      The MTHFR polymorphisms were detected in 72 microalbuminuric, 68 macroalbuminuric
      and 72 normoalbuinuric T2DM patients by PCR-RFLP. RESULTS: The possession of both
      MTHFR 677T and 1298C alleles increase the risk of microalbuminuria to 4.3-fold
      (p=0.007) in T2DM patients. The presence of either MTHFR 677T, 1298C allele is
      sufficient to increase the risk of macroalbuminuria in T2DM patients by 4.1 and
      5.5 times (p=0.027, and p=0.006, respectively). The concomitant presence of both
      677T and 1298C alleles act in synergy to increase the risk of macroalbuminuria by
      20.4-fold (p<0.001) and progression of DN from microalbuminuria to
      macroalbuminuria (OR=4.73, p=0.01). CONCLUSION: Both MTHFR 677T and 1298C alleles
      increased the susceptibility to the onset and progression of DN in Iranians with
      T2DM.

PMID- 20800058
TI  - Time of sampling is crucial for measurement of cell-free plasma DNA following
      acute aseptic inflammation induced by exercise.
AB  - OBJECTIVES: To determine the time-course changes of cell-free plasma DNA (cfDNA)
      following heavy exercise. METHODS: cfDNA concentration, C-reactive protein levels
      (hs-CRP), uric acid concentration (UA), creatine kinase activity (CK) were
      measured before and post-exercise (immediately post, 0.5h, 1h, 2h, 3h, 4h, 5h,
      6h, 8h, 10h, 24h). RESULTS: cfDNA increased (15-fold) 30-min post-exercise and
      normalized thereafter. hs-CRP increased (56%, p<0.001) 1h post-exercise, remained
      elevated throughout recovery (52-142%, p<0.0001), and peaked (200% rise,
      p<0.0001) at 24h post-exercise. UA and CK increased (p<0.05), immediately post
      exercise, remained elevated throughout recovery (p<0.0001), and peaked (p<0.0001)
      at 24h of post-exercise recovery. CONCLUSIONS: cfDNA sampling timing is crucial
      and a potential source of error following aseptic inflammation.

PMID- 20800059
TI  - Low DHA and plasmalogens associated with a precise PUFA-rich diet devoid of DHA.
AB  - OBJECTIVES: Fatty acids, being multi-functional and partially diet-dependent, are
      crucial for health yet optimal dietary composition remains controversial.
      Previous work suggests that nutritionally-dependent populations live with
      significant fatty acid abnormalities despite abundant polyunsaturated fatty acid
      intake. DESIGN AND METHODS: An analysis of fasting plasma phospholipids,
      including plasmalogens, and total fatty acids was conducted on twelve tube-fed
      people receiving a uniform diet which meets current polyunsaturated fatty acid
      intake recommendations, specifically, linoleic acid as 8.1% of energy and alpha
      linolenic acid as 1.3% of energy for at least two years. RESULTS:
      Eicosapentaenoic- and docosahexaenoic acid-related phospholipids were low. In
      addition, C16:0- and C18:0-related plasmalogens, components of phospholipids,
      were low. Essential fatty acid deficiency as classically defined was not present.
      CONCLUSIONS: Based upon extensive clinical investigations in neuro-typical
      people, abnormalities of these key cell-membrane components may have undesirable
      clinical consequences. In particular, docosahexaenoic acid sufficiency needs to
      be assured. Comprehensive re-evaluation of current recommendations may be
      necessary.

PMID- 20800060
TI  - Migration and differentiation potential of stem cells in the cnidarian
      Hydractinia analysed in eGFP-transgenic animals and chimeras.
AB  - To analyse cell migration and the differentiation potential of migratory stem
      cells in Hydractinia, we generated animals with an eGFP reporter gene stably
      expressed and transmitted via the germline. The transgene was placed under the
      control of two different actin promoters and the promoter of elongation factor
      1alpha. One actin promoter (Act-II) and the EF-1alpha promoter enabled expression
      of the transgene in all cells, the other actin promoter (Act-I) in epithelial and
      gametogenic cells, but not in the pluripotent migratory stem cells. We produced
      chimeric animals consisting of histocompatible wild type and transgenic parts.
      When the transgene was under the control of the epithelial cell specific actin-I
      promoter, non-fluorescent transgenic stem cells immigrated into wild type tissue,
      stopped migration and differentiated into epithelial cells which then commenced
      eGFP-expression. Migratory stem cells are therefore pluripotent and can give rise
      not only to germ cells, nematocytes and nerve cells, but also to epithelial
      cells. While in somatic cells expression of the act-I promoter was restricted to
      epithelial cells it became also active in gametogenesis. The act-I gene is
      expressed in spermatogonia, oogonia and oocytes. In males the expression pattern
      showed that migratory stem cells are the precursors of both the spermatogonia and
      their somatic envelopes. Comparative expression studies using the promoters of
      the actin-II gene and the elongation factor-1alpha gene revealed the potential of
      transgenic techniques to trace the development of the nervous system.

PMID- 20800061
TI  - Differential expression of Toll-like receptors in follicular lymphoma, diffuse
      large B-cell lymphoma and peripheral T-cell lymphoma.
AB  - Although Toll-like receptors (TLRs) in mammals are well-known to play important
      roles in innate immunity, newer roles for the TLRs have suggested that cells with
      aberrant TLR expression may have a survival advantage over normal cells.
      Lymphocytes are one of a small number of cell types that express many of the
      TLRs, suggesting that abnormal TLR levels/signaling may potentially influence the
      progression of malignant lymphomas. Thus, frozen samples of 51 lymph nodes from
      patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL) and
      peripheral T-cell lymphoma (PTCL) were analyzed for the expression of TLR1 to 9
      using quantitative real-time PCR, and compared to those in reactive
      lymphadenopathy (RL) samples. TLR2 was over-expressed in both DLBCL and PTCL but
      not in FL when compared to RL. TLR1 and TLR4 expression was up-regulated in PTCL,
      while TLR8 was highly expressed in DLBCL. Although TLR5 showed lower expression
      in FL, expression of TLR3, TLR6, TLR7 and TLR9 did not vary significantly between
      different lymphoma subtypes. Double immunostaining revealed an increase in the
      number of TLR2 and/or TLR8 expressing lymphoma cells in DLBCL. In PTCL, TLR2 and
      TLR4 expression was localized to neoplastic T cells. TLR expression is highly
      variable among lymphoma subtypes. However, despite this some significant
      differences exist that may prove useful in the development of novel therapeutic
      strategies.

PMID- 20800062
TI  - A model for signaling specificity of Wnt/Frizzled combinations through co
      receptor recruitment.
AB  - Wnts control mammalian developmental morphogenesis and are critical for adult
      stem cell maintenance. Wnts initiate several intracellular signaling cascades,
      such as Wnt/beta-catenin-, Wnt/Ca(2+)- and Wnt/ROR2-signaling. Signaling
      preference of Wnts for these various pathways is thought to depend on the
      repertoire of receptors present on recipient cells. Here, we propose a further
      refinement of this receptor model and hypothesize that Wnt signaling specificity
      depends on co-receptor recruitment upon binding of Wnt to Frizzled receptor
      molecules. In this model, recruitment of LRP5/6 leads to activation of Wnt/beta
      catenin signaling, whereas signaling through other pathways is mediated by
      recruiting ROR2.

PMID- 20800063
TI  - Mechanism of hCG-induced spermiation in the toad Rhinella arenarum (Amphibia,
      Anura).
AB  - In Rhinella arenarum spermiation occurs as a consequence of LH/FSH increase
      during the amplexus or by a single dose of hCG, among other gonadotropins. The
      present study employs an in vitro system to study the mechanism of action of hCG
      in the spermiation of R. arenarum. Testicular fragments were incubated for 2h at
      28 degrees C in the presence or absence of 20IU hCG with or without different
      PKA/PKC inhibitors and activators as well as ouabain and amiloride as Na(+)/K(+)
      ATPase and transcellular Na(+) transport inhibitors, respectively. Ouabain did
      not induce spermiation in absence of hCG and inhibited hCG-induced spermiation in
      a dose-dependent manner, reaching 90% inhibition with the higher concentration.
      In contrast, amiloride neither affected spermiation nor steroidogenesis.
      Activation of PKA with 8Br-cAMP induced spermiation in the absence of hCG while
      its inhibition with H89 blocked hCG action. On the other hand, PKC inhibition
      with Bi or STP did not affect hCG-induced spermiation although PKC activation
      significantly decreased hCG-dependent sperm release. These results suggest that
      PKC inhibits spermiation but also that the inhibition exerted by the kinase could
      be blocked by hCG. Taken together, these observations could indicate that PKA is
      involved in the mechanism of the gonadotropin action, mechanism also requiring
      the activation of a non-pumping Na(+)/K(+) ATPase pathway.

PMID- 20800065
TI  - Expression, purification and characterization of recombinant interleukin-21.
AB  - Interleukin-21 (IL-21) is a key regulator of the immune system. However, studies
      of this cytokine have so far been hampered by the limited availability of
      recombinant protein preparations. Here we describe a method based on refolding of
      inclusion bodies expressed in E. coli by rapid dilution. The method was applied
      to human and murine IL-21 proteins, which were further purified by affinity
      chromatography and gel-filtration. The proteins are pure and highly active as
      determined by endotoxin and cell proliferation assays. The availability of
      milligram quantities of protein enabled us to generate monoclonal antibody
      fragments against the cytokine and will aid in further structural, biochemical
      and physiological analyses.

PMID- 20800064
TI  - Hormonally mediated epigenetic changes to steroid receptors in the developing
      brain: implications for sexual differentiation.
AB  - The establishment of sex-specific neural morphology, which underlies sex-specific
      behaviors, occurs during a perinatal sensitive window in which brief exposure to
      gonadal steroid hormones produces permanent masculinization of the brain. In the
      rodent, estradiol derived from testicular androgens is a principal organizational
      hormone. The mechanism by which transient estradiol exposure induces permanent
      differences in neuronal anatomy has been widely investigated, but remains
      elusive. Epigenetic changes, such as DNA methylation, allow environmental
      influences to alter long-term gene expression patterns and therefore may be a
      potential mediator of estradiol-induced organization of the neonatal brain. Here
      we review data that demonstrate sex and estradiol-induced differences in DNA
      methylation on the estrogen receptor alpha (ERalpha), estrogen receptor beta
      (ERbeta), and progesterone receptor (PR) promoters in sexually dimorphic brain
      regions across development. Contrary to the overarching view of DNA methylation
      as a permanent modification directly tied to gene expression, these data
      demonstrate that methylation patterns on steroid hormone receptors change across
      the life span and do not necessarily predict expression. Although further
      exploration into the mechanism and significance of estradiol-induced alterations
      in DNA methylation patterns in the neonatal brain is necessary, these results
      provide preliminary evidence that epigenetic alterations can occur in response to
      early hormone exposure and may mediate estradiol-induced organization of sex
      differences in the neonatal brain.

PMID- 20800066
TI  - Novel application of Ki67 to quantify antigen-specific in vitro
      lymphoproliferation.
AB  - Antigen-specific proliferation is a critical function of memory T cells that is
      often utilised to measure vaccine immunogenicity and T cell function. We proposed
      that measurement of intracellular expression of the nuclear protein, Ki67, could
      reliably assess specific T cell proliferation in vitro. Ki67 was expressed in
      CD4+ and CD8+ T cells that had undergone in vitro proliferation after 6-day
      culture of human whole blood or PBMC with antigens. T cells cultured with no
      antigen did not express Ki67. When compared to current flow cytometry based
      proliferation assays, Ki67 detected proliferating cells with greater sensitivity
      than BrdU incorporation, whereas its sensitivity was similar to dye dilution of
      Oregon Green (OG), a CFSE derivative. Overall, the magnitude and cytokine
      expression profile of proliferating T cells detected by Ki67 expression
      correlated strongly with T cells detected with BrdU or OG. The intra-assay
      variability of Ki67 proliferation was 2-3% for CD4+ T cells, and 10-16% for CD8+
      T cells. Finally, we demonstrate that the Ki67 assay detects tetanus toxoid
      specific CD4+ T cell proliferation after infant vaccination with tetanus toxoid
      (TT). Overall our data suggest that intracellular Ki67 expression provides a
      specific, quantitative and reproducible measure of antigen-specific T cell
      proliferation in vitro.

PMID- 20800068
TI  - The switch that does not flip: the blue-light receptor YtvA from Bacillus
      subtilis adopts an elongated dimer conformation independent of the activation
      state as revealed by a combined AUC and SAXS study.
AB  - Photoreceptors play an important role in plants and bacteria by converting
      extracellular stimuli into intracellular signals. One distinct class are the blue
      light-sensitive phototropins harboring a light-oxygen-voltage (LOV) domain
      coupled to various effector domains. Photon absorption by the chromophore within
      the LOV domain results in an activation of the output domain via mechanisms that
      are hitherto not well understood. The photoreceptor YtvA from Bacillus subtilis
      is a bacterial analog of phototropins, consists of an LOV and a sulfate
      transporter/anti-sigma factor antagonist domain, and is involved in the response
      of the bacterium to environmental stress. We present here analytical
      ultracentrifugation studies and small-angle X-ray scattering experiments, showing
      that YtvA is a dimer. On the basis of these results, we present a low-resolution
      model of the dimer in the dark and the lit state of the protein. In addition, we
      show that YtvA does not change its oligomerization state or its overall shape
      upon light activation.

PMID- 20800067
TI  - GRK2 as a novel gene therapy target in heart failure.
AB  - Despite significant advances in pharmacological and clinical treatment, heart
      failure (HF) remains a leading cause of morbidity and mortality worldwide. HF is
      a chronic and progressive clinical syndrome characterized by a reduction in left
      ventricular (LV) ejection fraction and adverse remodeling of the myocardium. The
      past several years have seen remarkable progress using animal models in
      unraveling the cellular and molecular mechanisms underlying HF pathogenesis and
      progression. These studies have revealed potentially novel therapeutic
      targets/strategies. The application of cardiac gene transfer, which allows for
      the manipulation of targets in cardiomyocytes, appears to be a promising
      therapeutic tool in HF. beta-adrenergic receptor (betaAR) dysfunction represents
      a hallmark abnormality of chronic HF, and increased G protein-coupled receptor
      kinase 2 (GRK2) levels/activity in failing myocardium is among these alterations.
      In the past 15years, several animal studies have shown that expression of a
      peptide inhibitor of GRK2 (betaARKct) can improve the contractile function of
      failing myocardium including promoting reverse remodeling of the LV. Therefore,
      data support the use of the betaARKct as a promising candidate for therapeutic
      application in human HF. Importantly, recent studies in cardiac-specific GRK2
      knockout mice have corroborated GRK2 being pathological in failing myocytes. The
      purpose of this review is to discuss: 1) the alterations of betaAR signaling that
      occur in HF, 2) the evidence from transgenic mouse studies investigating the
      impact of GRK2 manipulation in failing myocardium, 3) the therapeutic efficacy of
      in vivo betaARKct gene therapy in HF, and 4) the intriguing possibility of
      lowering HF-related sympathetic nervous system hyperactivity by inhibiting GRK2
      activity in the adrenal gland. This article is part of a Special Section entitled
      "Special Section: Cardiovascular Gene Therapy".

PMID- 20800069
TI  - Structural analysis of HMGD-DNA complexes reveals influence of intercalation on
      sequence selectivity and DNA bending.
AB  - The ubiquitous, eukaryotic, high-mobility group box (HMGB) chromosomal proteins
      promote many chromatin-mediated cellular activities through their non-sequence
      specific binding and bending of DNA. Minor-groove DNA binding by the HMG box
      results in substantial DNA bending toward the major groove owing to electrostatic
      interactions, shape complementarity, and DNA intercalation that occurs at two
      sites. Here, the structures of the complexes formed with DNA by a partially DNA
      intercalation-deficient mutant of Drosophila melanogaster HMGD have been
      determined by X-ray crystallography at a resolution of 2.85 A. The six proteins
      and 50 bp of DNA in the crystal structure revealed a variety of bound
      conformations. All of the proteins bound in the minor groove, bridging DNA
      molecules, presumably because these DNA regions are easily deformed. The loss of
      the primary site of DNA intercalation decreased overall DNA bending and shape
      complementarity. However, DNA bending at the secondary site of intercalation was
      retained and most protein-DNA contacts were preserved. The mode of binding
      resembles the HMGB1 box A-cisplatin-DNA complex, which also lacks a primary
      intercalating residue. This study provides new insights into the binding
      mechanisms used by HMG boxes to recognize varied DNA structures and sequences as
      well as modulate DNA structure and DNA bending.

PMID- 20800071
TI  - Oscillations in a size-structured prey-predator model.
AB  - This article introduces a predator-prey model with the prey structured by body
      size, based on reports in the literature that predation rates are prey-size
      specific. The model is built on the foundation of the one-species physiologically
      structured models studied earlier. Three types of equilibria are found:
      extinction, multiple prey-only equilibria and possibly multiple predator-prey
      coexistence equilibria. The stabilities of the equilibria are investigated.
      Comparison is made with the underlying ODE Lotka-Volterra model. It turns out
      that the ODE model can exhibit sustain oscillations if there is an Allee effect
      in the net reproduction rate, that is the net reproduction rate grows for some
      range of the prey's population size. In contrast, it is shown that the structured
      PDE model can exhibit sustain oscillations even if the net reproductive rate is
      strictly declining with prey population size. We find that predation, even size
      non-specific linear predation can destabilize a stable prey-only equilibrium, if
      reproduction is size specific and limited to individuals of large enough size.
      Furthermore, we show that size-specific predation can also destabilize the
      predator-prey equilibrium in the PDE model. We surmise that size-specific
      predation allows for temporary prey escape which is responsible for
      destabilization in the predator-prey dynamics.

PMID- 20800072
TI  - Determining the parametric structure of models.
AB  - In this paper we develop a comprehensive approach to determining the parametric
      structure of models. This involves considering whether a model is parameter
      redundant or not and investigating model identifiability. The approach adopted
      makes use of exhaustive summaries, quantities that uniquely define the model. We
      review and generalise previous work on evaluating the symbolic rank of an
      appropriate derivative matrix to detect parameter redundancy, and then develop
      further tools for use within this framework, based on a matrix decomposition.
      Complex models, where the symbolic rank is difficult to calculate, may be
      simplified structurally using reparameterisation and by finding a reduced-form
      exhaustive summary. The approach of the paper is illustrated using examples from
      ecology, compartment modelling and Bayes networks. This work is topical as models
      in the biosciences and elsewhere are becoming increasingly complex.

PMID- 20800070
TI  - Expression-system-dependent modulation of HIV-1 envelope glycoprotein
      antigenicity and immunogenicity.
AB  - Recombinant expression systems differ in the type of glycosylation they impart on
      expressed antigens such as the human immunodeficiency virus type 1 (HIV-1)
      envelope glycoproteins, potentially affecting their biological properties. We
      performed head-to-head antigenic, immunogenic and molecular profiling of two
      distantly related Env surface (gp120) antigens produced in different systems: (a)
      mammalian (293 FreeStyle cells; 293F) cells in the presence of kifunensine, which
      impart only high-mannose glycans; (b) insect cells (Spodoptera frugiperda, Sf9),
      which confer mainly paucimannosidic glycans; (c) Sf9 cells recombinant for
      mammalian glycosylation enzymes (Sf9 Mimic), which impart high-mannose, hybrid
      and complex glycans without sialic acid; and (d) 293F cells, which impart high
      mannose, hybrid and complex glycans with sialic acid. Molecular models revealed a
      significant difference in gp120 glycan coverage between the Sf9-derived and wild
      type mammalian-cell-derived material that is predicted to affect ligand binding
      sites proximal to glycans. Modeling of solvent-exposed surface electrostatic
      potentials showed that sialic acid imparts a significant negative surface charge
      that may influence gp120 antigenicity and immunogenicity. Gp120 expressed in
      systems that do not incorporate sialic acid displayed increased ligand binding to
      the CD4 binding and CD4-induced sites compared to those expressed in the system
      that do, and imparted other more subtle differences in antigenicity in a gp120
      subtype-specific manner. Non-sialic-acid-containing gp120 was significantly more
      immunogenic than the sialylated version when administered in two different
      adjuvants, and induced higher titers of antibodies competing for CD4 binding site
      ligand-gp120 interaction. These findings suggest that non-sialic-acid-imparting
      systems yield gp120 immunogens with modified antigenic and immunogenic
      properties, considerations that should be considered when selecting expression
      systems for glycosylated antigens to be used for structure-function studies and
      for vaccine use.

PMID- 20800073
TI  - The neuroprotective effects of tanshinone IIA on beta-amyloid-induced toxicity in
      rat cortical neurons.
AB  - Oxidative stress caused by amyloid beta-peptide (Abeta) may play an important
      role in the pathogenesis of Alzheimer disease (AD). Abeta is known to be directly
      responsible for the production of reactive oxygen species (ROS) and induction of
      apoptosis. Tanshinone IIA (Tan IIA) is extracted from a traditional herbal
      medicine Salvia miltiorrhiza BUNGE, which has been shown to protect against
      oxidative stress and cell death. In this study, we investigated the
      neuroprotective effect of Tan IIA against Abeta25-35-induced cell death in
      cultured cortical neurons. Exposure of cortical neurons to 30MUM Abeta25-35
      caused a significant viability loss, cell apoptosis and decreased activities of
      superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as
      increased levels of malondialdehyde (MDA) production. In parallel, Abeta25-35
      significant increased the intracellular ROS elevation and decreased mitochondrial
      membrane potential (MMP). However, pretreatment of the cells with Tan IIA prior
      to Abeta25-35 exposure suppressed these Abeta25-35-induced cellular events
      noticeably. In addition, Tan IIA reduced the Abeta25-35-induced increase of
      caspase-3 activity, and reduced cytochrome c translocation into the cytosol from
      mitochondria. Furthermore, Tan IIA also ameliorated the Abeta25-35-induced Bcl
      2/Bax ratio reduction in cortical neurons. Taken together, these data indicate
      that Tan IIA protected cultured cortical neurons against Abeta25-35-induced
      neurotoxicity through its antioxidative potential. Our results strongly suggest
      that Tan IIA may be effective in treating AD associated with oxidative stress.

PMID- 20800075
TI  - Sweet taste intensity is enhanced by temporal fluctuation of aroma and taste, and
      depends on phase shift.
AB  - Pulsatile stimulation enhances taste intensity compared to continuous stimulation
      with stimuli of the same net tastant concentration. In the present work, we
      studied the effects of pulsatile delivery of aroma and taste on their combined
      contribution to taste intensity. Effects on taste perception were evaluated for
      aroma and taste pulsation and the aroma pulse-taste pulse phase shift. High
      concentration sucrose pulses were alternated with water rinses every 2.5s. Four
      different aroma (isoamyl acetate) versions were presented: (1) no aroma, (2)
      continuous aroma (3) aroma pulses in-phase and (4) aroma pulses out-of-phase with
      taste pulses. Aroma-taste combinations were evaluated for sweetness intensity by
      a 15-member trained panel using time-intensity analysis. Sweetness intensity was
      enhanced by pulsatile stimulation of sucrose or isoamyl acetate. In addition,
      taste enhancement by aroma and tastant pulses was additive if both were presented
      out-of-phase which resulted a sweetness intensity enhancement by more than 35%
      compared to a continuous sucrose reference of the same net sucrose concentration.
      Aroma-induced sweetness enhancement can be explained by cross-modal aroma-taste
      integration. Amplification of aroma-taste integration by pulsatile stimulation
      may be attributed to a potentiated afferent input of aroma and taste information
      prior to aroma-taste integration. Alternative mechanisms include the importance
      of swallowing on aroma-taste integration.

PMID- 20800074
TI  - Prokineticin 2 suppresses GABA-activated current in rat primary sensory neurons.
AB  - Prokineticin 2 (PK2) is a newly identified regulatory protein, which is involved
      in a wide range of physiological processes including pain perception in mammals.
      However, the precise role of PK2 in nociception is yet not fully understood.
      Here, we investigate the effects of PK2 on GABA(A) receptor function in rat
      trigeminal ganglion neurons using whole-cell patch clamp technique. PK2
      reversibly depressed inward currents produced by GABA(A) receptor activation
      (I(GABA)) with an IC50 of 0.26 +/- 0.02 nM. PK2 appeared to decrease the efficacy
      of GABA to GABA(A) receptor but not the affinity. The maximum response of the
      GABA dose-response curve decreased to 71.2 +/- 7.0% of control after pretreatment
      with PK2, while the threshold value and EC50 of curve did not alter
      significantly. The effects of PK2 on I(GABA) were voltage independent. The PK2
      induced inhibition of I(GABA) was removed by intracellular dialysis of either GDP
      beta-S (a non-hydrolyzable GDP analog), EGTA (a Ca2+ chelator) or GF109203X (a
      selective protein kinase C inhibitor), but not by H89 (a protein kinase A
      inhibitor). These results suggest that PK2 down-regulates the function of the
      GABA(A) receptor via G-protein and protein kinase C dependent signal pathways in
      primary sensory neurons and this depression might underlie the hyperalgesia
      induced by PK2.

PMID- 20800076
TI  - Taste mixture interactions: suppression, additivity, and the predominance of
      sweetness.
AB  - Most of what is known about taste interactions has come from studies of binary
      mixtures. The primary goal of this study was to determine whether asymmetries in
      suppression between stimuli in binary mixtures predict the perception of tastes
      in more complex mixtures (e.g., ternary and quaternary mixtures). Also of
      interest was the longstanding question of whether overall taste intensity derives
      from the sum of the tastes perceived within a mixture (perceptual additivity) or
      from the sum of the perceived intensities of the individual stimuli (stimulus
      additivity). Using the general labeled magnitude scale together with a sip-and
      spit procedure, we asked subjects to rate overall taste intensity and the
      sweetness, sourness, saltiness and bitterness of approximately equi-intense
      sucrose, NaCl, citric acid and QSO(4) stimuli presented alone and in all possible
      binary, ternary and quaternary mixtures. The results showed a consistent pattern
      of mixture suppression in which sucrose sweetness tended to be both the least
      suppressed quality and the strongest suppressor of other tastes. The overall
      intensity of mixtures was found to be predicted best by perceptual additivity. A
      second experiment that was designed to rule out potentially confounding effects
      of the order of taste ratings and the temperature of taste solutions replicated
      the main findings of the first experiment. Overall, the results imply that
      mixture suppression favors perception of sweet carbohydrates in foods at the
      expense of other potentially harmful ingredients, such as high levels of sodium
      (saltiness) and potential poisons or spoilage (bitterness and sourness).

PMID- 20800077
TI  - Lateral facilitation revealed dichoptically for luminance-modulated and contrast
      modulated stimuli.
AB  - Foveal detection thresholds for LM and CM Gaussian blobs in the presence of
      visible, laterally placed blobs (separations of 0-6 degrees ) were measured
      monocularly and dichoptically in observers with normal vision. In the monocular
      and dichoptic viewing conditions, masking occurs for overlapping blobs, followed
      by facilitation when they are completely separated (2-8 blob sd units under
      monocular conditions and 4-12 blob sd units under dichoptic conditions). For LM
      blobs, facilitation of 24.1+/-0.07% is demonstrated dichoptically, less than the
      57.0+/-0.06% demonstrated monocularly. For CM blobs, more robust facilitation of
      39.0+/-0.02% is demonstrated dichoptically, slightly more than the 34.6+/-0.1%
      demonstrated monocularly. Lateral facilitation is thus not purely a monocular
      phenomenon. More robust dichoptic facilitation for CM stimuli suggests a more
      binocular locus for their neural processing.

PMID- 20800078
TI  - Ocular wavefront aberrations in the common marmoset Callithrix jacchus: effects
      of age and refractive error.
AB  - The common marmoset, Callithrix jacchus, is a primate model for emmetropization
      studies. The refractive development of the marmoset eye depends on visual
      experience, so knowledge of the optical quality of the eye is valuable. We report
      on the wavefront aberrations of the marmoset eye, measured with a clinical
      Hartmann-Shack aberrometer (COAS, AMO Wavefront Sciences). Aberrations were
      measured on both eyes of 23 marmosets whose ages ranged from 18 to 452 days.
      Twenty-one of the subjects were members of studies of emmetropization and
      accommodation, and two were untreated normal subjects. Eleven of the 21
      experimental subjects had worn monocular diffusers and 10 had worn binocular
      spectacle lenses of equal power. Monocular deprivation or lens rearing began at
      about 45 days of age and ended at about 108 days of age. All refractions and
      aberration measures were performed while the eyes were cyclopleged; most
      aberration measures were made while subjects were awake, but some control
      measurements were performed under anesthesia. Wavefront error was expressed as a
      seventh-order Zernike polynomial expansion, using the Optical Society of
      America's naming convention. Aberrations in young marmosets decreased up to about
      100 days of age, after which the higher-order RMS aberration leveled off to about
      0.10 MUm over a 3 mm diameter pupil. Higher-order aberrations were 1.8 times
      greater when the subjects were under general anesthesia than when they were
      awake. Young marmoset eyes were characterized by negative spherical aberration.
      Form-deprived eyes of the monocular deprivation animals had greater wavefront
      aberrations than their fellow untreated eyes, particularly for asymmetric
      aberrations in the odd-numbered Zernike orders. Both lens-treated and form
      deprived eyes showed similar significant increases in Z3(-3) trefoil aberration,
      suggesting the increase in trefoil may be related to factors that do not involve
      visual feedback.

PMID- 20800079
TI  - Results of a multi-media multiple behavior obesity prevention program for
      adolescents.
AB  - BACKGROUND: This study reports on effectiveness trial outcomes of Health in
      Motion, a computer tailored multiple behavior intervention for adolescents.
      METHODS: Using school as level of assignment, students (n=1800) from eight high
      schools in four states (RI, TN, MA, and NY) were stratified and randomly assigned
      to no treatment or a multi-media intervention for physical activity, fruit and
      vegetable consumption, and limited TV viewing between 2006 and 2007. RESULTS:
      Intervention effects on continuous outcomes, on movement to action and
      maintenance stages, and on stability within action and maintenance stages were
      evaluated using random effects modeling. Effects were most pronounced for fruit
      and vegetable consumption and for total risks across all time points and for each
      behavior immediately post intervention. Co-variation of behavior change occurred
      within the treatment group, where individuals progressing to action or
      maintenance for one behavior were 1.4-4.2 times more likely to make similar
      progress on another behavior. CONCLUSION: Health in Motion is an innovative,
      multiple behavior obesity prevention intervention relevant for all adolescents
      that relies solely on interactive technology to deliver tailored feedback. The
      outcomes of the effectiveness trial demonstrate both an ability to initiate
      behavior change across multiple energy balance behaviors simultaneously and
      feasibility for ease of dissemination.

PMID- 20800080
TI  - Mercury(II)-resistance transposons Tn502 and Tn512, from Pseudomonas clinical
      strains, are structurally different members of the Tn5053 family.
AB  - The mercury(II)-resistance transposons Tn502 and Tn512 were sequenced and shown
      to be members of the Tn5053 family. They are currently the sole representatives
      from the clinical setting and were obtained from geographically disparate
      Pseudomonas aeruginosa strains. The family is comprised of six novel transposons
      that display genetic and structural variability that has arisen in different
      ways. The mer and tni arms of the transposons can be differently combined,
      suggesting that chimeric interchanges have occurred, possibly mediated by the
      TniR resolvase. The mer modules within the mer arms are remnants of Tn21/Tn501
      like transposons that inserted into a tni-containing ancestral transposon. The
      mer modules themselves are polymorphic and that of Tn502 is a new type. It
      includes the putative urf2M gene, the 3'-end of which expresses a protein and
      hence is a bone fide gene (tniM). Homologues of tniM occur beyond the Tn5053
      family and include Tn21 tnpM. Other studies have implicated tniM and tnpM in
      transposition. Based on sequence and compositional differences, members of the
      environmentally widespread Tn5053 family constitute a different lineage from the
      related and clinically successful intI-containing Tn402 family.

PMID- 20800081
TI  - Imaging of cellular therapies.
AB  - Cellular therapy promises to revolutionize medicine, by restoring tissue and
      organ function, and combating key disorders including cancer. As with all major
      developments, new tools must be introduced to allow optimization. For cell
      therapy, the key tool is in vivo imaging for real time assessment of parameters
      such as cell localization, numbers and viability. Such data is critical to
      modulate and tailor the therapy for each patient. In this review, we discuss
      recent work in the field of imaging cell therapies in the clinic, including
      preclinical work where clinical examples are not yet available. Clinical trials
      in which transferred cells were imaged using magnetic resonance imaging (MRI),
      nuclear scintigraphy, single photon emission computed tomography (SPECT), and
      positron emission tomography (PET) are evaluated from an imaging perspective.
      Preclinical cell tracking studies that focus on fluorescence and bioluminescence
      imaging are excluded, as these modalities are generally not applicable to
      clinical cell tracking. In this review, we assess the advantages and drawbacks of
      the various imaging techniques available, focusing on immune cells, particularly
      dendritic cells. Both strategies of prelabeling cells before transplant and the
      use of an injectable label to target cells in situ are covered. Finally, we
      discuss future developments, including the emergence of multimodal imaging
      technology for cell tracking from the preclinical to the clinical realm.

PMID- 20800082
TI  - Comparison of four different treatment conditions of extended exposure in the in
      vitro micronucleus assay using TK6 lymphoblastoid cells.
AB  - In the OECD Guideline 487, a total of four extended exposure treatment conditions
      are proposed for the in vitro micronucleus (MNvit) assay in the presence and
      absence of a cytokinesis block and with or without a recovery period. This
      guideline also states that rodent cell lines and human lymphocytes can be used as
      shown by many validated studies but that human cell lines such as TK6 and HepG2
      are not yet validated. In this present study each extended exposure condition was
      characterized by investigation using TK6 cells and nine chemicals known to be
      able to induce micronucleus (MN) in rodent cell lines. The results revealed two
      concerns: six chemicals did not show significant MN induction in the 'cytokinesis
      block without recovery period'; two aneugens showed no dose-dependent
      cytotoxicity in the 'cytokinesis block with recovery period'. Further
      investigation revealed that 3-4 times higher spontaneous MN frequency than that
      in the other conditions is a possible reason for the low sensitivity, and this
      high spontaneous MN frequency was not observed in Chinese hamster lung cells
      under the identical treatment condition. With regard to the two conditions
      without cytokinesis block, two negative substances were evaluated and found to be
      negative, suggesting the validity of the TK6 test system for these conditions.
      Although our findings showed a few concerns for the treatment with cytokinesis
      block, the TK6 cells were considered to be a reliable cell line to be used for
      detecting potential inducers of MN in the in vitro micronucleus assay based on
      the overall results.

PMID- 20800084
TI  - Benchmark dose approaches in chemical health risk assessment in relation to
      number and distress of laboratory animals.
AB  - Use of benchmark dose (BMD) approaches is expected to increase substantially,
      with growing awareness among researchers and inclusion in regulatory testing
      guidance documents such as REACH. The BMD approach has clear advantages over the
      No-Observed-Adverse-Effect-Level (NOAEL) approach in defining toxicological
      thresholds, risk levels, and points of departure as the basis for setting
      guidance and limit values. Several aspects of the BMD may increase the use of
      laboratory animals; the optimal number of dose groups for BMD calculation is
      between five and ten, rather than the current standard of four; also, experiments
      with more animals will result in narrow confidence intervals. However, this paper
      presents several counterarguments suggesting that design of experiments suited
      for BMD analyses might be used to decrease the distress and use of laboratory
      animals. If experiments are performed with unequal group size, with fewer animals
      in the high response dose groups and more animals close to toxicological
      threshold, the aggregated distress might be reduced. In addition, there is a need
      to evaluate how the total number of animals affects the quality of BMD (e.g. in
      terms of confidence intervals). Development of strategies for optimal design of
      experiments requires tools which evaluate experimental designs from an ethical
      perspective; a concept of distress-adjusted number of animals is suggested.

PMID- 20800083
TI  - Respiratory safety pharmacology: concurrent validation of volume, rate, time,
      flow and ratio variables in conscious male Sprague-Dawley rats.
AB  - This study compares basic respiratory variables (rate, tidal and minute volumes)
      with time-, flow- and ratio-derived parameters obtained using head-out
      plethysmography in rats following administration of reference drugs (isotonic
      saline, 2.0 mL/kg, IV; albuterol, 400 MUg/kg, inhalation; methacholine, 136
      MUg/kg, IV; and remifentanil, 14 MUg/kg, IV) to identify respiratory variables
      with superior sensitivity. Paired t-tests by block-period, and analysis of
      covariance (ANCOVA) with baseline as covariate and a posteriori pair-wise
      comparisons using Dunnett's test were used. Variations in respiratory parameters
      observed over time justify the use of a control group in any respiratory safety
      pharmacology study for inter-groups comparison. Handling-, and slumbering-,
      induced perturbations were minimal. The system was sensitive and specific to
      detect changes in respiratory variables related to pharmacologically-induced
      bronchodilation, bronchoconstriction and central respiratory depression. The
      standard variables (respiratory rate, tidal and minute volumes) confirmed to be
      the cornerstone of respiratory safety pharmacology to detect pharmacological
      changes. Flow-derived parameters appeared as highly valuable complement for
      interpretation of respiratory response, whereas time- and ratio-derived
      parameters presented limited added value during interpretation.

PMID- 20800085
TI  - SRD5A2 is associated with increased cortisol metabolism in schizophrenia spectrum
      disorders.
AB  - OBJECTIVE: Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is
      documented in bipolar disorder and schizophrenia, but the mechanism is unclear;
      recently, increased activity of cortisol metabolizing enzymes was indicated in
      these disorders. We investigated whether five genes involved in cortisol
      metabolism were associated with altered activity of cortisol metabolizing enzymes
      in bipolar disorder (BD) and schizophrenia spectrum disorders (SCZ). METHODS: A
      case-control sample of subjects with BD (N=213), SCZ (N=274) and healthy controls
      (N=370) from Oslo, Norway, were included and genotyped from 2003 to 2008. A sub
      sample (healthy controls: N=151; SCZ: N=40; BD: N=39) had estimated enzyme
      activities based on measurements of urinary free cortisol, urinary free cortisone
      and metabolites. A total of 102 single nucleotide polymorphisms (SNPs) in the
      SRD5A1, SRD5A2, AKR1D1, HSD11B1 and HSD11B2 genes were genotyped, and significant
      SNPs analyzed in the sub-sample. RESULTS: There was a significant association of
      rs6732223 in SRD5A2 (5alpha-reductase) with SCZ (p=0.0043, Bonferroni corrected
      p=0.030, T risk allele). There was a significantly increased 5alpha-reductase
      activity associated with rs6732223 (T allele) within the SCZ group (p=0.011).
      CONCLUSIONS: The present data suggest an interaction between SCZ and SRD5A2
      variants coding for the enzyme 5alpha-reductase, giving rise to increased 5alpha
      reductase activity in SCZ. The findings may have implications for cortisol
      metabolizing enzymes as possible drug targets.

PMID- 20800086
TI  - A validated bioanalytical method in mouse, rat, rabbit and human plasma for the
      quantification of one of the steroid glycosides found in Hoodia gordonii extract.
AB  - Hoodia gordonii extract contains steroid glycosides, fatty acids, plant sterols
      and polar organic material. Certain steroid glycosides show appetite suppressant
      activities following oral ingestion. This study describes the validation of a
      bioanalytical method for the quantification of one of the steroid glycosides,
      H.g.-12 (~ 10% (w/w) of the extract), in mouse, rat, rabbit and human plasma. The
      method utilises a liquid-liquid extraction with methyl-tert-butyl ether followed
      by chromatographic separation on a 2.1 * 50 mm C(18) Genesis high performance
      liquid chromatography (HPLC) column and detection on a triple quadrupole mass
      spectrometer. Detection of H.g.-12 and its stable isotope internal standards is
      performed using positive TurboIonsprayTM ionisation in multiple reaction
      monitoring mode. The validation procedure demonstrated assay sensitivity,
      linearity, accuracy, precision and selectivity over the calibration range of 0.5
      150 ng/mL in human plasma (500 MUL sample volume), 1.0-100 ng/mL in rat and
      rabbit plasma (150 MUL sample volume) and 1.0-250 ng/mL in mouse plasma (150 MUL
      sample volume) with good recoveries (>= 77%). H.g.-12 was stable in plasma for >=
      6 months at -20 degrees C, for up to 4h at ambient temperature (ca22 degrees C)
      and after 3 freeze-thaw cycles. Plasma extracts were stable for up to 24h at
      ambient temperature.

PMID- 20800087
TI  - CGX, a traditional Korean medicine ameliorates concanavalin A-induced acute liver
      injury.
AB  - Concanavalin A (Con A)-induced acute liver injury model is well established as a
      model of T cell-mediated liver injury, in which T cells and NKT cells exert their
      cytotoxicity towards liver cells. In this study, we investigated the protective
      effects of CGX, a traditional Korean medicine against Con A-induced liver injury
      and its underlying mechanisms. After pretreatment with CGX (po, 50, 100 or 200
      mg/kg) or distilled water once daily during 7 days, Con A (15 mg/kg) was injected
      intravenously. Thereafter serum level of AST and ALT, lipid peroxidation and
      cytokines in the liver tissue, and immune cell population in blood and the spleen
      were analyzed. CGX treatment reduced serum ALT, AST level in a dose-dependent
      manner. CGX treatment significantly decreased the lipid peroxidation and
      glutathione depletion in the liver tissue, and also lowered tissue levels of
      tumor necrotic factor-alpha and interferon-gamma. CGX treatment attenuated the
      compositional alteration of Tc, Th, NKT, and B cells in blood as well as in the
      spleen. These results suggest that CGX has hepatoprotective property against Con
      A-induced liver injury through antioxidant action and immune regulation.

PMID- 20800088
TI  - Cystatins--Extra- and intracellular cysteine protease inhibitors: High-level
      secretion and uptake of cystatin C in human neuroblastoma cells.
AB  - Cystatins are present in mammals, birds, fish, insects, plants, fungi and
      protozoa and constitute a large protein family, with most members sharing a
      cysteine protease inhibitory function. In humans 12 functional cystatins exist,
      forming three groups based on molecular organisation and distribution in the
      organism. The type 1 cystatins (A and B) are known as intracellular, type 2
      cystatins (C, D, E/M, F, G, S, SN and SA) extracellular and type 3 cystatins (L-
      and H-kininogen) intravascular proteins. The present paper is focused on the
      human cystatins and especially those of type 2, which are directed (with signal
      peptides) for cellular export following translation. Results indicating existence
      of systems for significant internalisation of type 2 cystatins from the
      extracellular to intracellular compartments are reviewed. Data showing that human
      neuroblastoma cell lines generally secrete high levels, but also contain high
      amounts of cystatin C are presented. Culturing of these cells in medium
      containing cystatin C at concentrations found in body fluids resulted in
      increased intracellular cystatin C, as a result of an uptake process. At
      immunofluorescence cytochemistry a pronounced vesicular cystatin C staining was
      observed. The simplistic denotation of the type 2 cystatins as extracellular
      inhibitors is thus challenged, and possible biological functions of the
      internalised cystatins are discussed. To illustrate the special case of high
      cellular cystatin content seen in cells of patients with hereditary cystatin C
      amyloid angiopathy, expression vectors for wild-type and L68Q mutated cystatin C
      were used to transfect SK-N-BE(2) cells. Clones overexpressing the two variants
      showed increased secreted levels of cystatin C. Within the cells the L68Q variant
      appeared to mainly localise to the endoplasmic reticulum rather than to acidic
      vesicular organelles, indicating limitations in the transport out from the cell
      rather than increased uptake as explanation for the elevated cellular cystatin
      levels seen in hereditary cystatin C amyloid angiopathy.

PMID- 20800089
TI  - Single-pair FRET experiments on nucleosome conformational dynamics.
AB  - Nucleosomes, the basic units of DNA compaction in eukaryotes, play a crucial role
      in regulating all processes involving DNA, including transcription, replication
      and repair. Nucleosomes modulate DNA accessibility through conformational
      dynamics like DNA breathing - the transient unwrapping of DNA from the
      nucleosome, repositioning of nucleosomes along the DNA, or partial dissociation.
      Single molecule techniques, in particular single-pair Fluorescence Resonance
      Energy Transfer (spFRET), have resolved such conformational dynamics in
      individual nucleosomes. Here, we review the results of FRET experiments on single
      nucleosomes, including fluorescence correlation spectroscopy (FCS), confocal
      single molecule microscopy on freely diffusing nucleosomes and widefield total
      internal reflection fluorescence (TIRF) microscopy on immobilized nucleosomes.
      The combined spFRET studies on single nucleosomes reveal a very dynamic
      organization of the nucleosome, that has been shown to be modulated by post
      translational modifications of the histones and by DNA sequence.

PMID- 20800090
TI  - Schisandrin B co-treatment ameliorates the impairment on mitochondrial
      antioxidant status in various tissues of long-term ethanol treated rats.
AB  - The effect of schisandrin B (Sch B) on long-term ethanol-induced oxidative stress
      in various rat tissues was investigated. Long-term ethanol treatment increased
      reactive oxygen metabolites (ROM) level in plasma. The ethanol-induced oxidative
      stress was assessed by mitochondrial glutathione and alpha-tocopherol levels,
      antioxidant enzyme activities, malondialdehyde (mtMDA) production and heat shock
      protein (Hsp) 25/70 levels. Liver was most susceptible to oxidative stress with a
      significant increase in mtMDA production. Long-term Sch B treatment enhanced
      mitochondrial antioxidant status in a tissue non-specific manner. Sch B co
      treatment ameliorated the alterations in plasma ROM levels, mtMDA production and
      Hsp 25/70 expression in rat tissues.

PMID- 20800091
TI  - Accumulation of pyrethroid compounds in primary cultures from rat cortex.
AB  - Recent studies have demonstrated that lipophilic compounds (e.g., methylmercury,
      polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDEs))
      rapidly accumulate in cells in culture to concentrations much higher than in the
      surrounding media. Primary cultures of neurons have been widely utilized to study
      the actions of pyrethroids, yet pyrethroid accumulation in these cells has not
      been studied to date. To test the hypothesis that pyrethroids rapidly accumulate
      in neurons in vitro, the time (0-90 min) and concentration (0.05-10 MUM)
      dependent accumulation of [(3)H]-deltamethrin (DM), [(3)H]-bifenthrin (BF) and
      [(14)C]-cis permethrin (PM) into primary cortical cultures was examined.
      Accumulation of all three pyrethroids was time- and concentration-dependent, with
      only small differences observed between the compounds. Concentration-dependent
      accumulation of PM and BF were similar, achieving a of total ~0.25 nmol in cells
      after 30 min in a 10 MUM solution. DM accumulation was lower, reaching a maximum
      of 0.14 nmol after 30 min in a 10 MUM solution. In 1 MUM solutions, DM and PM
      content in cells were 0.039 and 0.038 nmol after 90 min. At all concentrations
      and times, pyrethroid accumulation in cells was less than 5% of the total mass
      applied for DM and PM, and was less than 8% for BF. However, after 90 min,
      accumulation of all three compounds increased to as much as ~30-50-fold higher
      than the surrounding medium. The amount of compound recovered in the media at the
      end of incubation ranged from ~77% to 89%; the remainder (6-15%) was presumed to
      bind to the plastic of the culture plates. These results demonstrate rapid time-
      and concentration-dependent accumulation of pyrethroids in neurons in vitro.
      Further, for the three pyrethroids examined, there were not statistically
      significant differences in their accumulation. This data will be useful for
      making comparisons between in vivo and in vitro studies regarding effective
      concentrations of pyrethroids.

PMID- 20800093
TI  - Appraisal of translocation pathways for displaying ankyrin repeat protein on
      phage particles.
AB  - Depending on the molecular properties of the proteins of interest (POI), the rate
      of success in displaying proteins on phage particles is unpredictable. Formation
      of polypeptide tertiary structure in the cytoplasm occasionally results in low
      level display on viral particles. Here we assessed the influence of different
      leader peptides on the display of a premature cytoplasmic folding protein,
      ankyrin repeat protein (ARP), via the minor coat protein pIII. These peptides
      include the Sec, SRP and Tat pathways. The results demonstrated that the Sec and
      SRP pathways were capable of displaying the protein on the viral particle,
      whereas the Tat pathway failed to do so. Interestingly, the Tat pathway
      efficiently directed ARP through its translocon without fusing with pIII.
      Furthermore, the soluble form of ARP was detected in Escherichia coli periplasm.

PMID- 20800092
TI  - Candida albicans heme oxygenase and its product CO contribute to pathogenesis of
      candidemia and alter systemic chemokine and cytokine expression.
AB  - Mammalian heme oxygenases play important roles in immune regulation by producing
      immunosuppressive CO. The pathogenic yeast Candida albicans encodes a heme
      oxygenase, Hmx1, that is specifically induced by the host protein hemoglobin,
      suggesting a role in the pathogenesis of disseminated bloodstream infections. We
      show that exposing mice to therapeutic levels of CO increases C. albicans
      virulence, whereas an HMX1 null strain has decreased virulence in murine
      disseminated candidiasis. Levels of several regulatory cytokines and chemokines
      are decreased in mice infected with the null strain, and initial lesions in the
      kidney are more rapidly cleared after polymorphonuclear leukocyte infiltration.
      Reconstitution of one or both alleles restores virulence to the level of wild
      type. Growth in vitro and initial organ burdens in infected mice are not
      decreased and host iron overload does not restore virulence for the null strain,
      suggesting that early growth in the host is not limited by Hmx1-mediated iron
      scavenging. In contrast, inhaled CO partially reverses the virulence defect of
      the null strain and restores several host cytokine responses to wild-type levels.
      Collectively, these results show that C. albicans Hmx1 expression and CO
      production limit the host immune response and contribute to the pathogenesis of
      candidemia.

PMID- 20800094
TI  - Finite element modelling of cell wall properties for onion epidermis using a
      fibre-reinforced hyperelastic model.
AB  - A combined finite element method and inverse modelling approach is used to model
      the mechanical deformation of onion epidermis. A fibre-reinforced hyperelastic
      composite material model considering the fibre distribution has been used to
      simulate the mechanical behaviour of samples under tension. The mechanical
      parameters of onion epidermis are determined using an inverse modelling approach.
      The simulated results show a good correlation with experimental observations.

PMID- 20800095
TI  - Multivariate analysis of MRI data for Alzheimer's disease, mild cognitive
      impairment and healthy controls.
AB  - We have used multivariate data analysis, more specifically orthogonal partial
      least squares to latent structures (OPLS) analysis, to discriminate between
      Alzheimer's disease (AD), mild cognitive impairment (MCI) and elderly control
      subjects combining both regional and global magnetic resonance imaging (MRI)
      volumetric measures. In this study, 117 AD patients, 122 MCI patients and 112
      control subjects (from the AddNeuroMed study) were included. High-resolution
      sagittal 3D MP-RAGE datasets were acquired from each subject. Automated regional
      segmentation and manual outlining of the hippocampus were performed for each
      image. Altogether this yielded volumes of 24 different anatomically defined
      structures which were used for OPLS analysis. 17 randomly selected AD patients,
      12 randomly selected control subjects and the 22 MCI subjects who converted to AD
      at 1-year follow up were excluded from the initial OPLS analysis to provide a
      small external test set for model validation. Comparing AD with controls we found
      a sensitivity of 87% and a specificity of 90% using hippocampal measures alone.
      Combining both global and regional measures resulted in a sensitivity of 90% and
      a specificity of 94%. This increase in sensitivity and specificity resulted in an
      increase of the positive likelihood ratio from 9 to 15. From the external test
      set, the model predicted 82% of the AD patients and 83% of the control subjects
      correctly. Finally, 73% of the MCI subjects which converted to AD at 1 year
      follow-up were shown to resemble AD patients more closely than controls. This
      method shows potential for distinguishing between different patient groups.
      Combining the different MRI measures together resulted in a significantly better
      classification than using them separately. OPLS also shows potential for
      predicting conversion from MCI to AD.

PMID- 20800096
TI  - Functional connectivity in resting-state fMRI: is linear correlation sufficient?
AB  - Functional connectivity (FC) analysis is a prominent approach to analyzing fMRI
      data, especially acquired under the resting state condition. The commonly used
      linear correlation FC measure bears an implicit assumption of Gaussianity of the
      dependence structure. If only the marginals, but not all the bivariate
      distributions are Gaussian, linear correlation consistently underestimates the
      strength of the dependence. To assess the suitability of linear correlation and
      the general potential of nonlinear FC measures, we present a framework for
      testing and estimating the deviation from Gaussianity by means of comparing
      mutual information in the data and its Gaussianized counterpart. We apply this
      method to 24 sessions of human resting state fMRI. For each session, matrix of
      connectivities between 90 anatomical parcel time series is computed using mutual
      information and compared to results from its multivariate Gaussian surrogate that
      conserves the correlations but cancels any nonlinearity. While the group-level
      tests confirmed non-Gaussianity in the FC, the quantitative assessment revealed
      that the portion of mutual information neglected by linear correlation is
      relatively minor-on average only about 5% of the mutual information already
      captured by the linear correlation. The marginality of the non-Gaussianity was
      confirmed in comparisons using clustering of the parcels-the disagreement between
      clustering obtained from mutual information and linear correlation was
      attributable to random error. We conclude that for this type of data, practical
      relevance of nonlinear methods trying to improve over linear correlation might be
      limited by the fact that the data are indeed almost Gaussian.

PMID- 20800098
TI  - Evolutionary diversification of the genus Theba (Gastropoda: Helicidae) in space
      and time: a land snail conquering islands and continents.
AB  - Among oceanic islands, the Canary Islands offer exceptional opportunities for
      studying speciation processes due to their habitat diversity and well documented
      geological history. Based on a combined COI+ITS1 data set for more than 140
      specimens, we studied the diversification of the land snail genus Theba on the
      Canary Islands and adjacent African and European continental areas. Phylogenetic
      analyses resulted in the recognition of 18 genetically distinct clades including
      at least three new species. Divergence time estimates suggested an evolution of
      Theba in the Canarian archipelago and an initial radiation on the three eastern
      most islands during the Late Oligocene/Early Miocene. Despite the close proximity
      of NW Africa to the Canary Islands, the main mode of diversification was intra
      archipelago speciation rather than independent colonization of the islands from
      the mainland. Notably, species from Morocco are nested among species from the
      Canary Islands, indicating re-colonization of the continent from the islands. The
      re-colonization of NW Africa occurred during the Middle Miocene and led to a
      remarkable continental radiation.

PMID- 20800097
TI  - Regional reproducibility of pulsed arterial spin labeling perfusion imaging at
      3T.
AB  - Arterial spin labeling (ASL) is a promising non-invasive magnetic resonance
      imaging (MRI) technique for measuring regional cerebral blood flow (rCBF) or
      perfusion in vivo. To evaluate the feasibility of ASL as a biomarker for clinical
      trials, it is important to examine test-retest reproducibility. We investigated
      both inter- and intra-session reproducibility of perfusion MRI using a pulsed ASL
      (PASL) sequence PICORE Q2TIPS with an echo-planar imaging (EPI) readout.
      Structural MRI regions of interest (ROIs) were extracted individually by
      automated parcellation and segmentation methods using FreeSurfer. These cortical
      and subcortical ROIs were used to assess regional perfusion stability. Our
      results indicated regional variability in grey matter rCBF. Although rCBF
      measurements were characterized by intersubject variation, our results also
      indicated relatively less within-subject variability estimated as within-subject
      standard deviation (SD(W)) (intersession SD(W): 2.0 to 8.8; intrasession SD(W):
      2.8 to 9.6) and acceptable reliabilities as measured using intraclass correlation
      coefficient (ICC) (intersession ICC: 0.68 to 0.94; intrasession ICC: 0.66 to
      0.95) for regional MRI perfusion measurements using the PICORE Q2TIPS technique.
      Overall, our findings suggest that PASL is a technique with good within and
      between session reproducibility. Further reproducibility studies in target
      populations relevant for specific clinical trials of neurovascular related agents
      will be important and the present results provide a framework for such
      assessments.

PMID- 20800099
TI  - The genus Drosophila as a model for testing tree- and character-based methods of
      species identification using DNA barcoding.
AB  - DNA barcoding has recently been proposed as a promising tool for the (1) rapid
      assignment of unknown samples to described species by non-expert workers and (2)
      a potential method of new species discovery based on degree of DNA sequence
      divergence. Two broad methods have been used, one based on degree of DNA sequence
      variation, within and between species and another requiring the recovery of
      species as discrete clades (monophyly) on a phylogenetic tree. An alternative
      method relies on the identification of a set of specific diagnostic nucleotides
      for a given species (characters). The genus Drosophila has long served as a model
      system in genetics, development, ecology and evolutionary biology. As a result of
      this work, species boundaries within this genus are quite well delimited, with
      most taxa being defined by morphological characters and also conforming to a
      biological species concept (e.g., partial or complete reproductive isolation has
      used to erect and define species). In addition, some of the species in this group
      have also been subjected to phylogenetic analysis, yielding cases where taxa both
      conform and conflict with a phylogenetic species concept. Here, we analyzed 1058
      COI sequences belonging to 68 species belonging to Drosophila and its allied
      genus Zaprionus and with more than a single representative to assess the
      performance of the three DNA barcoding methods. 26% of the species could not be
      defined using distance methods, i.e. had a barcoding gap of <= 0, and 23% were
      not monophyletic. We focused then on four groups of closely-related species whose
      taxonomy is well-established on non-molecular basis (e.g., morphology, geography,
      reproductive isolation) and to which most of the problematic species belonged. We
      showed that characters performed better than other approaches in the case of
      paraphyletic species, but all methods failed in the case of polyphyletic species.
      For these polyphyletic species, other sources of evidence (e.g., morphology,
      geography, reproductive isolation) are more relevant than COI sequences,
      highlighting the limitation of DNA barcoding and the needs for integrative
      taxonomy approaches. In conclusion, DNA barcoding of Drosophila shows no reason
      to alter the 250 years old tradition of character-based taxonomy, and many
      reasons to shy away from the alternatives.

PMID- 20800100
TI  - Maintenance of enriched environment-induced changes of auditory spatial
      sensitivity and expression of GABAA, NMDA, and AMPA receptor subunits in rat
      auditory cortex.
AB  - Enriched environment (EE) has an important role in the development and plasticity
      of the brain. In this study, we investigated the maintenance of early EE exposure
      induced changes of spatial sensitivity, and the possible underlying mechanisms of
      this maintenance. We found that, compared with the age-matched control, the
      spatial sensitivity of A1 neurons was still enhanced after EE rats had been
      returned to the normal condition for 2 months. The enhancement was expressed by a
      sharper frequency tuning curve, smaller spatial receptive field, and a more
      selective directional curve of the early EE-exposed rats. Simultaneously, we
      detected significant increases in GABA(A) receptor alpha1, beta3 subunits; NMDA
      receptor NR2A, NR2B subunits; AMPA receptor GluR2 subunit protein expression; and
      in the ratios of GABA(A)alpha1/GABA(A)alpha3 and NR2A/NR2B. In particular, the
      expression ratio change of the GABA(A)alpha1/GABA(A)alpha3 was significant
      greater than that of NR2A/NR2B in early EE-exposed rats. These observations
      indicate that the persistent higher expression levels of the GABAergic and
      glutamatergic receptors expression induced by early EE exposure, especially
      enhancement of GABAergic inhibition in the auditory cortex, might be responsible
      for the maintenance of improved effects in auditory spatial sensitivity after the
      rats had been returned to the normal condition.

PMID- 20800101
TI  - Parathelypteriside attenuates cognition deficits in d-galactose treated mice by
      increasing antioxidant capacity and improving long-term potentiation.
AB  - Parathelypteriside (PG), a stilbenoid compound, was extracted from
      Parathelypteris glanduligera (kze.) ching that exhibits antioxidative and anti
      inflammatory effects. The aim of this study was to investigate the protective
      effect of PG against the d-galactose (d-gal)-induced neurotoxicity in mice. It
      was found that long-term intraperitoneal (i.p.) injection of PG (5 or 10 mg/(kg
      day)) for two weeks significantly improved the behavioral performance of d-gal
      treated mice in both Morris water maze test and step-down avoidance test.
      Biochemical examination revealed that PG reduced the increased levels of
      malondialdehyde (MDA), and attenuated the decreased activities of superoxide
      dismutase (SOD), glutathione peroxidase (GPx) and catalase in the hippocampus of
      d-gal-treated mice. Furthermore, the electrophysiological assay showed that PG
      significantly rescued the long-term potentiation (LTP) impairment in mice
      hippocampus, and western blotting analysis indicated that the effects of PG on
      LTP might be attributed to the activation of cAMP-response element-binding
      protein (CREB). Together, these results suggested that the natural product PG
      represented a potential source of medicine for the treatment of the
      neurodegenerative diseases.

PMID- 20800102
TI  - Cortisol enhances neural differentiation during fear acquisition and extinction
      in contingency aware young women.
AB  - Previously, we observed cortisol induced enhancement of neural fear acquisition
      in women. Yet, less is known about cortisol effects on neural fear extinction.
      Via differential fear conditioning, we explored cortisol effects on acquisition
      and extinction. Twenty contingency aware women taking monophasic oral
      contraceptives were included; 10 received placebo, 10 cortisol before
      conditioning. Group differences emerged in anterior cingulate cortex (ACC),
      hippocampus, and--as trend--in insula and thalamus during acquisition and in
      hippocampus, thalamus, and--as trend--in amygdala, insula, and ACC during
      extinction. During acquisition group differences were due to higher responses to
      the CS+ than to the CS- in the cortisol group. Notably, during extinction, group
      differences were due to higher responses to the CS- than to the CS+ in this
      group. Thus, cortisol induced a fear acquisition and extinction specific enhanced
      neural differentiation.

PMID- 20800104
TI  - A Mycobacterium ulcerans toxin, mycolactone, induces apoptosis in primary human
      keratinocytes and in HaCaT cells.
AB  - The pathogenicity of Mycobacterium ulcerans (Buruli ulcer) depends on cytotoxic
      effect of its exotoxin mycolactone. Since epidermis represents a barrier against
      infectious agents and balanced apoptosis is essential in epidermal homeostasis,
      we explored if mycolactone A/B induces apoptosis on two human keratinocyte
      populations, stem cells (KSC) and transit amplifying cells (TAC), and on human
      keratinocyte line, HaCaT. Treatment of TAC with 1 and 10 ng/ml mycolactone
      induced 60 and 90% apoptosis. KSC were more resistant than TAC: 50 and 75% of
      cells underwent apoptosis after 10 and 100 ng/ml toxin-treatment. Higher doses
      (1000 ng/ml) induced about 30% apoptosis on HaCaT. In contrast, mycolactone A/B
      was devoid of toxicity neither on human hepatoma HuH7 nor on human embryonic
      kidney HEK 293 T cell lines. In conclusion, mycolactone induces apoptosis in
      human keratinocytes, thus contributing to Buruli ulcer lesions development.

PMID- 20800103
TI  - Availability of cord blood extends allogeneic hematopoietic stem cell transplant
      access to racial and ethnic minorities.
AB  - Allogeneic transplant access can be severely limited for patients of racial and
      ethnic minorities without suitable sibling donors. Whether cord blood (CB)
      transplantation can extend transplant access because of the reduced stringency of
      required HLA-match is not proven. We prospectively evaluated availability of
      unrelated donors (URD) and CB according to patient ancestry in 553 patients
      without suitable sibling donors. URDs had priority if adequate donors were
      available. Otherwise >=4/6 HLA-matched CB grafts were chosen utilizing double
      units to augment graft dose. Patients had highly diverse ancestries including 35%
      non-Europeans. In 525 patients undergoing combined searches, 10/10 HLA-matched
      URDs were identified in 53% of those with European ancestry, but only 21% of
      patients with non-European origins (P < .001). However, the majority of both
      groups had 5-6/6 CB units. The 269 URD transplant recipients were predominantly
      European, with non-European patients accounting for only 23%. By contrast, 56% of
      CB transplant recipients had non-European ancestries (P < .001). Of 26 patients
      without any suitable stem cell source, 73% had non-European ancestries (P <
      .001). Their median weight was significantly higher than CB transplant recipients
      (P <.001), partially accounting for their lack of a CB graft. Availability of CB
      significantly extends allo-transplant access, especially in non-European
      patients, and has the greatest potential to provide a suitable stem cell source
      regardless of race or ethnicity. Minority patients in need of allografts, but
      without suitable matched sibling donors, should be referred for combined URD and
      CB searches to optimize transplant access.

PMID- 20800105
TI  - Identification and development of a promising novel mumps vaccine candidate
      strain.
AB  - Mumps epidemics are usually caused by airborne transmission of mumps virus (MuV)
      and have high morbidity in non-immunized children. Epidemiological studies in
      many regions of China show that the genotype F viral strain is the most
      prevalent. However, the genotype A strain is currently used to prepare vaccines.
      Regional epidemiological MuV data suggest a significant application for the
      development of live attenuated mumps vaccines targeting specific genotypes. This
      article reports the isolation and culture of a genotype F MuV candidate strain
      that could be used to prepare a live attenuated mumps vaccine. This strain is
      shown to have good immunological efficacy and stability in neurovirulence
      evaluations. This work should facilitate the implementation of mumps vaccination
      in mainland China by targeting the most prevalent MuV genotype, genotype F.

PMID- 20800106
TI  - vSPARQL: a view definition language for the semantic web.
AB  - Translational medicine applications would like to leverage the biological and
      biomedical ontologies, vocabularies, and data sets available on the semantic web.
      We present a general solution for RDF information set reuse inspired by database
      views. Our view definition language, vSPARQL, allows applications to specify the
      exact content that they are interested in and how that content should be
      restructured or modified. Applications can access relevant content by querying
      against these view definitions. We evaluate the expressivity of our approach by
      defining views for practical use cases and comparing our view definition language
      to existing query languages.

PMID- 20800107
TI  - Using an ECG reference ontology for semantic interoperability of ECG data.
AB  - In this paper we test the hypothesis that a domain reference ontology of the
      electrocardiogram (ECG) can be employed in an effective manner to achieve
      semantic integration between ECG data standards. Several standardization
      initiatives, namely AHA/MIT-BIH (Physionet), SCP-ECG and HL7 aECG, have led to
      heterogeneous conceptualizations of the ECG domain. We then argue that a shared
      anchor, the biomedical reality under scrutiny, can effectively support the
      semantic integration of these ECG standards into a coherent ECG representation
      for the sake of a unified Electronic Health Record (EHR) model. Our hypothesis is
      tested by means of an integration experiment that uses, on the one hand, an ECG
      Ontology and, on the other hand, elicited conceptual models of the ECG standards.
      As a conclusion, we attest the hypothesis and also provide an integration table
      depicting correspondence links between entities in the ECG Ontology and elements
      in the ECG standards.

PMID- 20800108
TI  - Pathogenesis of achalasia: lessons from mutant mice.

PMID- 20800109
TI  - DLC1 and liver cancer: the Akt connection.

PMID- 20800110
TI  - In the absence of HCV infection, interferon stimulated gene expression in liver
      is not associated with IL28B genotype.

PMID- 20800111
TI  - Antibody persistence in young adults 1 year after MMR immunization by aerosol or
      by subcutaneous route.
AB  - Information on antibody persistence after aerosol revaccination with MMR
      components is limited. Thus, antibody titers were determined in 283 adult
      participants in a MMR vaccine trial 12 months after revaccination. One group had
      received aerosolized Triviraten vaccine while two other groups received either
      injected Triviraten or MMR II vaccine. Both MMR vaccines contained the same
      rubella strain, but different measles and mumps strains. Seropositivity to
      measles persisted in 98% of aerosolized vaccine recipients, 92% of injected
      Triviraten, and 95% of injected MMR II. All participants in the three groups
      retained seropositivity to rubella, while less than 50% remained seropositive to
      mumps.

PMID- 20800112
TI  - Rubella: serosusceptibility among Egyptian females in late childhood and
      childbearing period.
AB  - Our objective was to determine age-specific rubella susceptibility among Egyptian
      females. This was a cross-sectional survey in eight randomly selected
      communities, with the largest number of reported rubella cases in the 2007
      Rubella surveillance. A sample of 5672 females between the ages of 6 and 45 years
      were interviewed. Of those 602 blood samples were obtained and tested for rubella
      IgG. The proportion of seronegative females was 9.7%. The highest proportion of
      susceptible females was in the ages between 6 and 25 years and the highest risk
      of susceptibility was among unmarried females [odds ratio (OR)=7.2]. The
      knowledge of interviewed females about rubella, the vaccine and the effect
      rubella infection on pregnancy and on the fetus was very limited. In conclusion
      more vaccination coverage is needed, with simultaneous increase of public
      awareness to minimize the susceptible female population.

PMID- 20800113
TI  - Induction of protective and therapeutic antitumor immunity by a DNA vaccine with
      C3d as a molecular adjuvant.
AB  - Although the critical role of complement component C3d as a molecular adjuvant in
      preventing virus infection is well established, its role in cancer therapies is
      unclear. In this study, we have engineered a DNA vaccine that expresses
      extracellular region of murine VEGFR-2 (FLK1(265-2493)) and 3 copies of C3d
      (C3d3), a component of complement as a molecular adjuvant, designed to increase
      antitumor immunity. VEGFR-2 has a more restricted expression on endothelial cells
      and is upregulated once these cells proliferate during angiogenesis in the tumor
      vasculature. Immunization of mice with vector encoding FLK1(265-2493) alone
      generated only background levels of anti-VEGFR-2 antibodies and slight inhibitory
      effect on tumor growth. However, the addition of C3d3 to the vaccine construct
      significantly augmented the anti-VEGFR-2 humoral immune response and inhibited
      the tumor growth. The antitumor activity induced by vaccination with vector
      encoding FLK1(265-2493)-C3d3 fusion protein was also demonstrated via growth
      inhibition of established tumors following passive transfer of immune serum from
      vaccinated mice. Our results suggest that vaccination with vector encoding
      FLK1(265-2493) with C3d3 as a molecular adjuvant induces adaptive humoral
      activity, which is directed against the murine VEGFR-2 and can significantly
      inhibit tumor growth, and that administration of C3d as a molecular adjuvant to
      increase antibodies levels to VEGFR-2 may provide an alternative treatment
      modality for cancer therapies.

PMID- 20800115
TI  - Sweet obsession, bitter facts.

PMID- 20800114
TI  - HMGB1-derived peptide acts as adjuvant inducing immune responses to peptide and
      protein antigen.
AB  - There is a need for new adjuvants that will induce immune responses to subunit
      vaccines. We show that a short peptide, named Hp91, whose sequence corresponds to
      an area within the endogenous molecule high mobility group box (HMGB1) protein 1
      potentiates cellular immune responses to peptide antigen and cellular and humoral
      immune responses to protein antigen in vivo. Hp91 promoted the in vivo production
      of the immunomodulatory cytokines, IFN-gamma, TNF-alpha, IL-6, and IL-12 (p70),
      as well as antigen-specific activation of CD8+ T cells. These results demonstrate
      the ability of a short immunostimulatory peptide to serve as an adjuvant for
      subunit vaccines.

PMID- 20800116
TI  - ADA value: Innovation.

PMID- 20800117
TI  - A national approach to restaurant menu labeling: the Patient Protection and
      Affordable Health Care Act, Section 4205.

PMID- 20800118
TI  - Registered dietitians and speech-language pathologists: an important partnership
      in Dysphagia management.

PMID- 20800119
TI  - Weighing in on added sugars and health.

PMID- 20800120
TI  - Are ethanol and fructose similar?

PMID- 20800121
TI  - Perceived benefits, barriers, and strategies of family meals among children with
      type 1 diabetes mellitus and their parents: focus-group findings.
AB  - Dietary management of type 1 diabetes mellitus has become much less restrictive
      and more flexible in recent years due to contemporary insulin regimens, which may
      afford families of children with type 1 diabetes mellitus greater ease in sharing
      family meals. Although these treatment advancements might facilitate family
      meals, overall demands of diabetes management can influence family's perceived or
      actual ability to do so. Youths with type 1 diabetes mellitus (ages 8 to 20
      years) and parents participated in separate focus groups. Thirty-five youths with
      type 1 diabetes mellitus (mean age=15.1+/-3.6 years) and their parents
      participated in 21 focus groups (12 youth groups, nine parent groups). Although
      there was substantial variability in how often family meals occurred, both
      parents and youths consistently perceived family meals as valuable and enjoyable.
      The major barrier to family meals discussed by both youths and parents was busy
      schedules. Strategies for having family meals that were discussed by parents
      included shopping to ensure availability of the foods needed to prepare meals,
      planning, and cooking meals in advance, and using simplified cooking methods.
      These findings suggest that a family-focused approach to nutrition interventions
      in this population, as opposed to one targeting the child with diabetes only, can
      improve the chance for successful dietary change.

PMID- 20800122
TI  - Fructose: metabolic, hedonic, and societal parallels with ethanol.
AB  - Rates of fructose consumption continue to rise nationwide and have been linked to
      rising rates of obesity, type 2 diabetes, and metabolic syndrome. Because obesity
      has been equated with addiction, and because of their evolutionary commonalities,
      we chose to examine the metabolic, hedonic, and societal similarities between
      fructose and its fermentation byproduct ethanol. Elucidation of fructose
      metabolism in liver and fructose action in brain demonstrate three parallelisms
      with ethanol. First, hepatic fructose metabolism is similar to ethanol, as they
      both serve as substrates for de novo lipogenesis, and in the process both promote
      hepatic insulin resistance, dyslipidemia, and hepatic steatosis. Second,
      fructosylation of proteins with resultant superoxide formation can result in
      hepatic inflammation similar to acetaldehyde, an intermediary metabolite of
      ethanol. Lastly, by stimulating the "hedonic pathway" of the brain both directly
      and indirectly, fructose creates habituation, and possibly dependence; also
      paralleling ethanol. Thus, fructose induces alterations in both hepatic
      metabolism and central nervous system energy signaling, leading to a "vicious
      cycle" of excessive consumption and disease consistent with metabolic syndrome.
      On a societal level, the treatment of fructose as a commodity exhibits market
      similarities to ethanol. Analogous to ethanol, societal efforts to reduce
      fructose consumption will likely be necessary to combat the obesity epidemic.

PMID- 20800123
TI  - Snack selection influences nutrient intake, triglycerides, and bowel habits of
      adult women: a pilot study.
AB  - Because appropriate snacking can promote a healthy body weight and serve as an
      important contributor to a healthy diet for women, identification of suitable
      foods for incorporation between meals is essential. We investigated the influence
      of short-term (2 weeks) incorporation of 100-kcal servings of snacks of dried
      plums vs low-fat cookies twice daily on total energy and nutrient intake,
      biochemical parameters, and bowel habits in a randomized crossover design of two
      2-week trials separated by a 2-week wash-out period in 26 women aged 25 to 54
      years with a body mass index between 24 and 35. Incorporation of dried plums or
      low-fat cookies into the diet did not alter energy intake or weight; however,
      compared to cookies, dried plums promoted greater (P< or =0.05) intake of fiber,
      potassium, riboflavin, niacin, and calcium. Total fat intake tended (P=0.094) to
      decrease with dried plum consumption, as did cholesterol intake (P=0.098). Plasma
      triglyceride concentration remained unchanged (P>0.05) by dried plum consumption
      and was 17.0+/-29.2 mg/dL (0.19+/-0.33 mmol/L) higher (P< or =0.05) after
      consumption of low-fat cookies vs dried plums at the end of 2 weeks. Dried plums
      promoted a softer (P< or =0.05) stool consistency vs usual intake and in
      comparison to intake of low-fat cookies. These results suggest that relative to a
      commercially processed low-fat cookie snack, dried plums promote more favorable
      plasma triglyceride responses, improved dietary quality, and slightly improved
      bowel function.

PMID- 20800124
TI  - Population-specific short-form mini nutritional assessment with body mass index
      or calf circumference can predict risk of malnutrition in community-living or
      institutionalized elderly people in taiwan.
AB  - A simple, reliable, noninvasive, and easy-to-use instrument is important for
      successful monitoring of emerging nutrition problems in elderly people. The
      objectives of this study were to determine whether adoption of population
      specific body mass index (BMI) cutpoints would improve the predictive ability of
      the short-form Mini Nutritional Assessment (MNA) and whether calf circumference
      could be an acceptable alternative to BMI in the short-form MNA without
      compromising its predictive ability. Using convenience sampling, the study
      recruited 301 community-living, 109 care center-living, and 68 nursing home
      living elderly people, 65 years or older, as subjects. Subjects were evaluated
      with the short-form MNA in three versions: (a) the original, (b) Taiwan version 1
      (T1), that adopted population-specific BMI cutpoints, and (c) Taiwan version 2
      (T2), which substituted calf circumference for BMI, and with the long-form MNA-T2
      as a reference. The ability of the short forms to predict the long-form MNA-T2
      was evaluated with binary classification and analysis of receiver operating
      characteristic curves. Results were analyzed with an SPSS for Windows 12.0
      software package (version 12.0.1C, 2000, SPSS Inc, Chicago, IL). Results showed
      that adoption of population-specific anthropometric BMI cutpoints improved the
      predictive ability of the short-form MNA, whereas replacement of BMI with calf
      circumference further improved the predictive ability of the scale (kappa values
      of the binary classification tests were 0.596, 0.742, and 0.843 for community
      living; 0.560, 0.683, and 0.839 for care center-living; and 0.346, 0.454, and
      0.522 for nursing home-living elderly for the original, T1, and T2 MNA short-form
      versions, respectively). These results suggest that modification of a measurement
      tool according to cultural or anthropometric features of the target population is
      necessary. The study also shows that calf circumference can be an acceptable
      alternative to BMI in the short-form MNA. Because measuring calf circumference is
      easier and less time-consuming then measuring BMI, the modified tool can make
      periodic nutritional screening an easier job and routine nutritional screening a
      more realistic goal in geriatric care.

PMID- 20800125
TI  - The beneficial effect of family meals on obesity differs by race, sex, and
      household education: the national survey of children's health, 2003-2004.
AB  - Studies have indicated that family meals may be a protective factor for childhood
      obesity; however, limited evidence is available in children with different
      racial, socioeconomic, and individual characteristics. The purpose of this study
      was to examine family meal frequency as a protective factor for obesity in a US
      based sample of non-Hispanic white, non-Hispanic black, and Hispanic children age
      6 to 11 years, and to identify individual, familial, and socioeconomic factors
      that moderate this association. Data were from the 2003 National Survey of
      Children's Health (n=16,770). Multinomial logistic regression analyses were used
      to test the association between family meal frequency and weight status, and the
      moderating effects of household structure, education, poverty level, and sex, by
      racial group. Non-Hispanic white children who consumed family meals every day
      were less likely to be obese than those eating family meals zero or a few days
      per week. A moderating effect for sex was observed in non-Hispanic black children
      such that family meal frequency was marginally protective in boys but not in
      girls. Higher family meal frequency was a marginal risk factor for obesity in
      Hispanic boys from low-education households, but not in girls from similar
      households. In conclusion, family meals seem to be protective of obesity in non
      Hispanic white children and non-Hispanic black boys, whereas they may put
      Hispanic boys living in low-education households at risk. Greater emphasis is
      needed in future research on assessing why this association differs among
      different race/ethnic groups, and evaluating the influence of the quality and
      quantity of family meals on child obesity.

PMID- 20800127
TI  - Timely resolution of patient concerns improves post-discharge satisfaction.
AB  - This research examined the effectiveness of a Food and Nutrition Services (FNS)
      Patient Advocate program on post-discharge patient satisfaction. All inpatients
      (n=187) who rated their satisfaction with one or more of six FNS attributes as 3
      or lower (on a 5-point scale) during a 4-month time period were visited by the
      FNS Patient Advocate, as were other patients on the units. A questionnaire
      similar to the inpatient satisfaction questionnaire was sent post-discharge to
      patients visited by the FNS Patient Advocate (n=374); a total of 158 (42%)
      responded. Results indicated that most patients (73%) recalled their interaction
      with the FNS Patient Advocate and were highly satisfied with their interaction
      with the Advocate (mean=5.8 on 7-point scale). Comparison of inpatient and post
      discharge ratings of satisfaction indicated a significant improvement in ratings
      post-discharge for special/restricted diet explained (P<0.01), food temperature
      (P<0.001), food quality (P<0.001), courtesy of server (P<0.01), and likelihood of
      receiving ordered foods (P<0.01) by inpatients who gave ratings of 3 or lower for
      any item and were seen by the FNS Patient Advocate. Addressing patient concerns
      while the patient is in the hospital appeared to be an effective strategy in
      improving satisfaction ratings of those patients post-discharge.

PMID- 20800126
TI  - Dietary intake patterns of low-income urban african-american adolescents.
AB  - Unhealthy eating increases risks for chronic disease. Few studies have examined
      the multifaceted aspects of dietary intake of low-income, urban African-American
      adolescents. This study aimed to describe dietary patterns including energy,
      nutrients, food groups, and diet quality and to identify areas to guide future
      interventions. Baseline data for a school-based obesity prevention study were
      collected from 382 African-American adolescents (10- to 14-year-olds) from four
      Chicago, IL, public schools in 2003. Diet was assessed using a 152-item food
      frequency questionnaire. Diet quality was measured using a modified version of
      the US Department of Agriculture Healthy Eating Index (HEI) and compared to
      published estimates for a nationwide sample. Participants reported high energy
      intakes and several unhealthy eating patterns: 58.6% consumed one or more
      servings of sweetened beverages per day and 15.7% consumed three or more servings
      per day; average fried food consumption was high (1.4 servings/day), 58.4%
      consumed one or more serving per day; and 75% consumed three or more three snacks
      per day. Only 49% of participants met the recommended three servings of dairy
      foods per day. Compared to a national, mostly white sample, participants had
      lower HEI scores (P<0.05); mean score was 66.0+/-12.8 (100=maximum HEI score) vs
      70.3+/-13.0 in boys vs girls, one third had scores <60 ("needs improvement") and
      only 15% scored >80 ("good"). This study reveals key areas of problematic dietary
      patterns for future interventions targeting low-income African-American
      adolescents, including frequent intakes of calorie-dense, low nutrient-rich
      foods, such as fried foods, snacks, and sweetened beverages.

PMID- 20800128
TI  - Race, homelessness, and other environmental factors associated with the food
      purchasing behavior of low-income women.
AB  - Observance of the hunger-obesity paradox in urban Minnesota has ignited interest
      in the quality of low-income households' food purchases. This cross-sectional
      study investigated low-income, urban Minnesotan women's past-month food purchases
      and their associations with race, homelessness, and aspects of the food system,
      including food shelf (ie, food pantry) and food store usage, factors believed to
      influence food choice and grocery shopping behavior. The survey included
      demographics, the US Department of Agriculture's 18-item Household Food Security
      Survey Module, and grocery shopping questions related to food purchases and food
      stores visited in the past month. Participants were a convenience sample of 448
      low-income, urban Minnesotan women, and data were collected from February through
      May 2008. The sample was 44% African American, 35% American Indian, 10% white,
      and 11% other/mixed race; 37% were homeless. Rates of "less healthy" food group
      purchases were higher compared to "healthy" food group purchases. Significant
      racial differences were found with respect to purchasing healthy protein food
      groups (P<0.05 to P<0.01) but not fruits, vegetables, or whole grains.
      Homelessness reduced the odds of purchasing most food groups, regardless of
      nutrient density (P<0.05 to P<0.001). Food shelf and food store usage mainly
      increased the odds of purchasing "less healthy" food groups (P<0.05 to P<0.01).
      These findings may help registered dietitians strategize with low-income, urban
      women how to make best use of food resources within their local food system.

PMID- 20800129
TI  - Intake of lutein and zeaxanthin differ with age, sex, and ethnicity.
AB  - Lutein and zeaxanthin are carotenoids that are selectively taken up into the
      macula of the eye, where they may protect against development of age-related
      macular degeneration. Accurate assessment of their intakes is important in the
      understanding of their individual roles in eye health. Current dietary databases
      lack the appropriate information to ascertain valid dietary intakes of these
      individual nutrients. The purpose of this research is to determine intakes of
      lutein and zeaxanthin separately in the National Health and Nutrition Examination
      Survey (NHANES) 2003-2004. The top major food sources for lutein and zeaxanthin
      intake in NHANES 2003-2004 were analyzed for lutein and zeaxanthin by high
      performance liquid chromatography from June to August 2006. Results were applied
      to dietary data from 8,525 participants in NHANES 2003-2004. Lutein and
      zeaxanthin food contents were separated into lutein and zeaxanthin in the
      nutrient database. Mean intakes from two nonconsecutive 24-hour recalls were
      grouped into food groups based on nutrient composition; these were matched to the
      new database, and lutein and zeaxanthin intakes were calculated separately. Among
      all age groups, both sexes, and all ethnicities, intakes of lutein were greater
      than of zeaxanthin. Relative intake of zeaxanthin to lutein decreased with age,
      with zeaxanthin to lutein ratios lower in females. Zeaxanthin to lutein ratios in
      Mexican Americans was considerably greater than other ethnicities (other
      Hispanics, non-Hispanic white, non-Hispanic black, other races). Lower zeaxanthin
      to lutein ratios were measured in groups at risk for age-related macular
      degeneration (eg, older participants, females). Our findings suggest that the
      relative intake of lutein and zeaxanthin may be important to age-related macular
      degeneration risk. Future studies are needed to assess the individual
      associations of lutein and zeaxanthin in eye health.

PMID- 20800130
TI  - Involvement of young Australian adults in meal preparation: cross-sectional
      associations with sociodemographic factors and diet quality.
AB  - Involvement in meal preparation has the potential to affect diet quality, but has
      not been thoroughly investigated. The study aims were to describe the involvement
      of young adult men and women in meal preparation and to investigate whether
      extent of involvement was associated with diet quality. During 2004 to 2006, a
      national sample of 2,814 Australian adults aged 26 to 36 years completed a self
      administered questionnaire on demographics, diet, and lifestyle factors.
      Participants were asked to report who was usually responsible for preparing the
      main meal on working days. Responses were categorized as "myself," "shared," or
      "someone else." Diet quality was assessed by calculating the mean number of daily
      servings for each food group. Analysis of variance was used to test for
      differences in means of dietary intake data. More women (65%) than men (29%) had
      sole responsibility for meal preparation. Shared meal preparation was reported by
      23% of women and 27% of men. Factors associated with greater involvement in meal
      preparation included marital status, education, occupation, and physical
      activity. After adjusting for sociodemographic and lifestyle factors, men who
      prepared the main meal themselves had a higher intake of lean meat and
      alternatives. Women who shared the meal preparation had higher intakes of
      vegetables and dairy; however, these differences in diet quality were only small.
      These results suggest that strategies seeking to motivate greater involvement in
      meal preparation might not be sufficient to markedly improve diet quality in
      young Australian adults.

PMID- 20800131
TI  - How can I help my clients sort out the conflicting and confusing information
      regarding dietary supplements?

PMID- 20800132
TI  - A distracting stroke and the erythematous flag.

PMID- 20800133
TI  - Recurrent perirectal abscess.

PMID- 20800134
TI  - Massive subcutaneous emphysema after endoscopic retrograde
      cholangiopancreatography.

PMID- 20800135
TI  - Hyponatremia and pseudohyponatremia: first, do no harm.

PMID- 20800136
TI  - Anticoagulation for portal vein thrombosis in cirrhosis.

PMID- 20800138
TI  - Green jaundice revisited.

PMID- 20800139
TI  - Antiphospholipid syndrome and homozygous factor V Leiden mutation in a young
      patient with Libman-Sacks endocarditis and stroke.

PMID- 20800140
TI  - Unusual presentation of a common disease: disseminated tuberculosis in an
      immunocompetent patient.

PMID- 20800141
TI  - Metastatic hepatic actinomycosis.

PMID- 20800142
TI  - Balancing work, family and friends, and lifestyle.

PMID- 20800143
TI  - Office management of peripheral arterial disease.
AB  - Patients with peripheral arterial disease are at increased risk for all-cause
      mortality, cardiovascular mortality, and mortality from coronary artery disease.
      Smoking should be stopped, and hypertension, diabetes mellitus, and dyslipidemia
      should be treated. Statins reduce the incidence of intermittent claudication and
      increase exercise duration until the onset of intermittent claudication in
      patients with peripheral arterial disease and hypercholesterolemia. Antiplatelet
      drugs, such as aspirin or clopidogrel, angiotensin-converting enzyme inhibitors,
      and statins, should be given to all patients with peripheral arterial disease.
      Beta-blockers should be given if coronary artery disease is present. Exercise
      rehabilitation programs and cilostazol improve exercise time until the onset of
      intermittent claudication. Indications for lower-extremity angioplasty,
      preferably with stenting, or bypass surgery are incapacitating claudication
      interfering with work or lifestyle in patients; limb salvage in patients with
      limb-threatening ischemia as manifested by rest pain, nonhealing ulcers,
      infection, or gangrene; and vasculogenic impotence.

PMID- 20800144
TI  - The most important neurologic reflex!

PMID- 20800145
TI  - Those who forget their history are condemned to repeat it.

PMID- 20800146
TI  - Unexpected renal and liver failure.

PMID- 20800147
TI  - A pale version.

PMID- 20800148
TI  - A breath-taking change.

PMID- 20800149
TI  - Fainting with HIV.

PMID- 20800150
TI  - Higher cardiovascular disease prevalence and mortality among younger blacks
      compared to whites.
AB  - BACKGROUND: Blacks have higher rates of cardiovascular disease than whites. The
      age at which these differential rates emerge has not been fully examined.
      OBJECTIVE: We examined cardiovascular disease prevalence and mortality among
      black and white adults across the adult age spectrum and explored potential
      mediators of these differential disease prevalence rates. METHODS: We conducted a
      cross-sectional analysis of National Health and Nutrition Examination Survey data
      from 1999-2006. We estimated age-adjusted and age-specific prevalence ratios (PR)
      for cardiovascular disease (heart failure, stroke, or myocardial infarction) for
      blacks versus whites in adults aged 35 years and older and examined potential
      explanatory factors. From the National Compressed Mortality File 5-year aggregate
      file of 1999-2003, we determined age-specific cardiovascular disease mortality
      rates. RESULTS: In young adulthood, cardiovascular disease prevalence was higher
      in blacks than whites (35-44 years PR 1.9; 95% confidence interval [CI], 1.1
      3.4). The black-white PR decreased with each decade of advancing age (P for
      trend=.04), leading to a narrowing of the racial gap at older ages (65-74 years
      PR 1.2; 95% CI, 0.8-1.6; > or =75 years PR 1.0; 95% CI, 0.7-1.4). Clinical and
      socioeconomic factors mediated some, but not all, of the excess cardiovascular
      disease prevalence among young to middle-aged blacks. Over a quarter (28%) of all
      cardiovascular disease deaths among blacks occurred in those aged <65 years,
      compared with 13% among whites. CONCLUSIONS: Reducing black/white disparities in
      cardiovascular disease will require a focus on young and middle-aged blacks.

PMID- 20800151
TI  - The clinical and prognostic importance of positive blood cultures in adults.
AB  - BACKGROUND: Bloodstream infections are a major cause of morbidity and mortality
      in adults. Bloodstream infections should be reassessed periodically because of
      increased antibiotic resistance, more patients receiving immunomodulatory
      therapy, improved antiretroviral therapy, and acquisition of infection in health
      care settings other than hospitals. METHODS: We conducted retrospective
      assessment by infectious disease physicians of hospitalized adults with positive
      blood cultures at 3 academic medical centers. RESULTS: Two thousand two hundred
      seventy positive blood culture episodes occurred in 1706 patients. Of 2669
      isolates, 51% represented true infection, 41% contamination, and 8% unknown
      clinical significance. Although coagulase-negative staphylococci were most
      common, only 10% were clinically significant. Among 1225 true bloodstream
      infections, the most frequent isolates were Staphylococcus aureus, Escherichia
      coli, Enterococcus spp., Klebsiella pneumoniae, coagulase-negative staphylococci,
      Pseudomonas aeruginosa, Candida albicans, Enterobacter cloacae, and Serratia
      marcescens. Intravenous catheters were the most common primary source of
      bloodstream infection (23% of episodes). Most (81%) bloodstream infections were
      acquired in the hospital or other health care settings. Crude and attributable in
      hospital case-fatality ratios were 20% and 12%, respectively, lower than in
      previous studies. Increasing age, hypotension, absence of fever, hospital
      acquisition, extreme white blood cell count values, and the presence of the
      acquired immunodeficiency syndrome, malignancy, or renal disease were
      significantly associated with an increased risk of in-hospital attributable death
      in multivariable analysis. CONCLUSIONS: The proportion of bloodstream infections
      due to intravenous catheters is continuing to increase. Most episodes were
      acquired in the hospital or other health care setting. In-hospital case-fatality
      ratios have decreased compared with previous studies. Several previously
      identified factors associated with an increased mortality remain statistically
      significant.

PMID- 20800152
TI  - Obesity and prostate cancer detection: insights from three national surveys.
AB  - BACKGROUND: Previous studies suggest that obesity is associated with higher
      prostate cancer progression and mortality despite an association with lower
      prostate cancer incidence. This study aims to better understand these apparently
      inconsistent relationships among obese men by combining evidence from 3
      nationally representative cross-sectional surveys. METHODS: We evaluated
      relationships between obesity and 1) testosterone concentrations in the Third
      National Health and Nutrition Examination Survey (NHANES III; n=845); 2) prostate
      specific antigen (PSA) in NHANES 2001-2004 (n=2458); and 3) prostate biopsy rates
      in the National Health Interview Survey (NHIS 2000; n=4789) population. Mean
      testosterone, PSA concentrations, and biopsy rates were computed for Body Mass
      Index (BMI) categories. RESULTS: Testosterone concentrations were inversely
      associated with obesity (P-trend <.0001) in NHANES III. In NHANES 2001-2004,
      obese (BMI >35) versus lean (BMI <25) men were less likely to have PSA
      concentrations that reached the biopsy threshold of >4 ng/mL (3% vs 8%; P
      <.0001). Among NHIS participants, all BMI groups had similar rates of PSA testing
      (P=.24). However, among men who had PSA tests, 11% of men with BMI >30 versus 16%
      with BMI <25, achieved a PSA threshold of 4 ng/mL; P=.01. Furthermore, biopsy
      rates were lower among men with BMI >30 versus BMI <25 in NHIS participants (4.6%
      vs 5.8%; P=.05). CONCLUSIONS: Obesity was associated with lower PSA-driven biopsy
      rates. These data support further studies to test the hypothesis that obesity
      affects prostate cancer detection independent of prostate cancer risk by
      decreasing the PSA-driven biopsy rates.

PMID- 20800153
TI  - A prediction model for the risk of incident chronic kidney disease.
AB  - BACKGROUND: Chronic kidney disease is a health burden for the general population.
      We designed a cohort study to construct prediction models for chronic kidney
      disease in the Chinese population. METHODS: A total of 5168 participants were
      followed up during a median of 2.2 (interquartile range, 1.5-2.9) years, and 190
      individuals (3.7%) developed chronic kidney disease, defined by a glomerular
      filtration rate of less than 60 mL/min/1.73 m(2). RESULTS: We developed a point
      system to estimate chronic kidney disease risk at 4 years using the following
      variables: age (8 points), body mass index (2 points), diastolic blood pressure
      (2 points), and history of type 2 diabetes (1 point) and stroke (4 points) for
      the clinical model, with the addition of uric acid (2 points), postprandial
      glucose (1 point), hemoglobin A1c (1 point), and proteinuria 100 mg/dL or greater
      (6 points) for the biochemical model. Similar discrimination measures were found
      between the clinical model (area under the receiver operating characteristic
      curve, 0.768; 95% confidence interval (CI), 0.738-0.798) and the biochemical
      model (area under the receiver operating characteristic curve, 0.765; 95% CI,
      0.734-0.796). The area under the receiver operating characteristic curve of the
      clinical model was 0.667 (95% CI, 0.631-0.703) for the external validation data
      from community-based cohort participants. The optimal cutoff value for the
      clinical model was set as 7, with a sensitivity of 0.76 and a specificity of
      0.66. CONCLUSION: We constructed a clinical point-based model to predict the 4
      year incidence of chronic kidney disease. This prediction tool may help to target
      Chinese subjects at risk of developing chronic kidney disease.

PMID- 20800154
TI  - Management and outcomes of renal disease and acute myocardial infarction.
AB  - BACKGROUND: Contemporary trends in the management and outcomes of chronic kidney
      disease patients who develop an acute myocardial infarction have not been
      adequately described, particularly from the more generalizable perspective of a
      population-based investigation. METHODS: The study population consisted of 6219
      residents of the Worcester, Massachusetts, metropolitan area who were
      hospitalized with acute myocardial infarction in 6 annual periods between 1995
      and 2005. Patients were categorized as having preserved kidney function (n=3154),
      mild to moderate chronic kidney disease (n=2313), or severe chronic kidney
      disease (n=752) at the time of hospital admission. RESULTS: Patients with chronic
      kidney disease were more likely to be older, to have a greater prevalence of
      comorbidities, and to experience significant in-hospital complications or die
      during hospitalization in comparison with patients with preserved kidney
      function. Although patients with chronic kidney disease were less likely to
      receive effective cardiac medications or undergo coronary interventional
      procedures than patients without kidney disease, we observed a marked increase in
      the use of effective cardiac medications and coronary interventional procedures
      in patients with chronic kidney disease during the period under study. In
      hospital death rates declined over time among patients with chronic kidney
      disease, whereas these death rates remained unchanged among persons with normal
      kidney function. CONCLUSION: The results of this study in residents of a large
      New England metropolitan area provide insights into changing trends in the
      treatment and impact of chronic kidney disease in patients hospitalized with
      acute myocardial infarction.

PMID- 20800155
TI  - Clinical features of sarcoid rhinosinusitis.
AB  - OBJECTIVE: We asked if certain clinical features were useful predictors of
      sarcoid rhinosinusitis in general populations of patients with chronic
      rhinosinusitis. METHODS: Our patients with sarcoid rhinosinusitis and those from
      the literature formed the study group. A group of 21 randomly selected patients
      from The University of Mississippi Medical Center Allergy Clinic with chronic
      rhinosinusitis composed the control group. RESULTS: Our literature search
      identified 73 patients with sarcoid rhinosinusitis reported since 1999. Twenty
      patients met inclusion criteria and were added to 16 of our patients to compose
      the study group of 36 patients. The majority of the study group was African
      American (61%) and female (69%) and had pulmonary sarcoidosis (67%) and other
      forms of extrapulmonary sarcoidosis in addition to sarcoid rhinosinusitis (86%).
      The 5 most common upper respiratory signs/symptoms were nasal obstruction (86%),
      nasal crusting (47%), anosmia (44%), epistaxis (28%), and nasal polyposis (25%).
      Odds ratios for sarcoid rhinosinusitis were 2.5 for persistent nasal obstruction,
      7.7 for epistaxis, 16.0 for anosmia, and 18.8 for nasal crusting. For each
      symptom, the odds of sarcoid rhinosinusitis increased by 9.4 (95% confidence
      interval, 1.8-49.9). Nasal crusting was associated with the coexistence of
      atrophic rhinosinusitis at nasal endoscopy. Treatment with oral corticosteroids
      and other immunosuppressive therapy, primarily methotrexate, was frequently
      required. CONCLUSION: The coexistence of chronic rhinosinusitis and 2 of the
      signs of nasal crusting, anosmia, or epistaxis are highly specific for sarcoid
      rhinosinusitis. Even in the absence of an established diagnosis of sarcoidosis,
      sinonasal biopsy should be considered for diagnosing these patients with chronic
      rhinosinusitis.

PMID- 20800156
TI  - Lactation and maternal risk of type 2 diabetes: a population-based study.
AB  - BACKGROUND: Lactation has been associated with improvements in maternal glucose
      metabolism. METHODS: We explored the relationships between lactation and risk of
      type 2 diabetes in a well-characterized, population-representative cohort of
      women, aged 40-78 years, who were members of a large integrated health care
      delivery organization in California and enrolled in the Reproductive Risk factors
      for Incontinence Study at Kaiser (RRISK), between 2003 and 2008. Multivariable
      logistic regression was used to control for age, parity, race, education,
      hysterectomy, physical activity, tobacco and alcohol use, family history of
      diabetes, and body mass index while examining the impact of duration,
      exclusivity, and consistency of lactation on risk of having developed type 2
      diabetes. RESULTS: Of 2233 women studied, 1828 were mothers; 56% had breastfed an
      infant for > or =1 month. In fully adjusted models, the risk of type 2 diabetes
      among women who consistently breastfed all of their children for > or =1 month
      remained similar to that of women who had never given birth (odds ratio [OR]
      1.01; 95% confidence interval [CI], 0.56-1.81). In contrast, mothers who had
      never breastfed an infant were more likely to have developed type 2 diabetes than
      nulliparous women (OR 1.93; 95% CI, 1.14-3.27) [corrected]. Mothers who never
      exclusively breastfed were more likely to have developed type 2 diabetes than
      mothers who exclusively breastfed for 1-3 months (OR 1.52; 95% CI, 1.11-2.10).
      CONCLUSIONS: Risk of type 2 diabetes increases when term pregnancy is followed by
      <1 month of lactation, independent of physical activity and body mass index in
      later life. Mothers should be encouraged to exclusively breastfeed all of their
      infants for at least 1 month.

PMID- 20800157
TI  - Agreement between erythrocyte sedimentation rate and C-reactive protein in
      hospital practice.
AB  - BACKGROUND: Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are
      frequently prescribed jointly. The usefulness of this practice is uncertain.
      METHODS: All patients with ESR and CRP measured at the same time in an academic
      tertiary hospital during a 1-year period were included. Concomitant measures of
      serum creatinine, hematocrit, and anti-Xa activity were recorded to study
      noninflammatory cause of increased ESR. Level of agreement between ESR and CRP
      was assessed with kappa coefficient, and their accuracy was determined in a
      medical chart review of 99 randomly selected patients with disagreement between
      both markers. RESULTS: Among 5777 patients, 35% and 58% had an elevated CRP and
      ESR, respectively. ESR and CRP were in agreement in 67% of patients (both
      elevated in 30%, both normal in 37%). A disagreement was observed in 33%
      (elevated ESR/normal CRP in 28%, normal ESR/elevated CRP in 5%). The kappa
      coefficient showed poor agreement (k=0.38) between both markers. Review of
      medical chart showed that 25 patients with elevated CRP and normal ESR had an
      active inflammatory disease (false-negative ESR). Conversely, 74 patients had
      elevated ESR and normal CRP-32% had resolving inflammatory disorders, 28%
      disclosed a variable interfering with the ESR measure (false-positive ESR), 32%
      had unexplained discrepancies, and 8% had an active inflammatory disease (false
      negative CRP). CONCLUSION: In hospital practice, joint measurement of ESR and CRP
      is unwarranted. Because of slow variation and frequent confounding, ESR is
      frequently misleading in unselected patients. When an inflammatory disorder is
      suspected, priority should be given to CRP.

PMID- 20800158
TI  - Prognosis assessment of cardiac involvement in systemic AL amyloidosis by
      magnetic resonance imaging.
AB  - BACKGROUND: Cardiac involvement is one of the most important prognostic factors
      in systemic AL amyloidosis. The aim of our study was to assess the role of
      cardiovascular magnetic resonance (CMR) imaging in prognosis evaluation in AL
      amyloidosis. METHODS: We retrospectively analyzed 29 consecutive patients with AL
      amyloidosis who had undergone CMR. Clinical, laboratory, echocardiographic, and
      CMR characteristics were compared between CMR-positive (ie, with CMR signs of
      cardiac localization of AL amyloidosis) and CMR-negative patients. Univariate and
      multivariate analyses were performed to assess the prognostic value of positive
      CMR in comparison with other prognostic factors. RESULTS: CMR was positive in 11
      patients (38%). The overall survival rates for CMR-positive patients were 28%,
      14%, and 14% versus 84%, 77%, and 45% at 1, 2, and 5 years, respectively, for CMR
      negative patients (P=.002). Late gadolinium enhancement patterns, biventricular
      hypertrophy, and pericardial effusion on CMR were more frequent in nonsurvivors.
      Congestive heart failure, abnormal echocardiography, Eastern Cooperative Oncology
      Group grade >1, brain natriuretic peptide, and left ventricular ejection fraction
      <55% also were associated with a decreased survival. The presence of congestive
      heart failure was the only significant variable associated with survival on
      multivariate analysis. CONCLUSION: We found that the presence of a positive CMR
      in AL amyloidosis was associated with a significantly increased risk of death, in
      particular of cardiac origin, but was not independent of clinical congestive
      heart failure.

PMID- 20800159
TI  - AAIM Report on Master Teachers and Clinician Educators Part 2: faculty
      development and training.

PMID- 20800160
TI  - Watching in George Tooker's waiting room.

PMID- 20800161
TI  - Report of the AGA Institute Education and Training Committee Task Force on
      physician reentry.

PMID- 20800162
TI  - [Three-month course of rifampicin and isoniazid for the treatment of latent
      tuberculous infection].
AB  - BACKGROUND AND OBJECTIVES: Isoniazid (I) is the drug of choice for treating
      latent tuberculous infection (LTI). Duration of treatment with I and its liver
      toxicity represent a serious drawback for a correct enforceability. In several
      clinical guides, a 3-month course with rifampicin (Rif) and I is recommended as
      an acceptable alternative to the 6-9 month course with I. Here we present our
      experience with this new regimen. PATIENTS AND METHODS: From 2001, the 3-month
      regimen with Rif and I was offered to patients older than 14 years, who were
      recruited in the contacts study. A good adherence was considered when the patient
      manifested so and he/she went to the scheduled monthly controls. We performed
      baseline liver analyses in those patients at risk of hepatotoxicity and in all
      patients older than 35 years. In all cases, a liver laboratory control was done
      at the first month of treatment and whenever patients had symptoms suggestive of
      intolerance. Databases of tuberculosis controls and contacts were crossed to
      evaluate the number of individuals who developed tuberculosis. RESULTS: Between
      2000 and 2008, treatment for LTI was indicated in 547 contacts (7.8% refused
      treatment, 34.1% with the 6-month I course, 63.5% with the 3-month Rif and I
      course and 2.3% with other regimens). A total of 84.97% (147/173) patients with
      the 6-month I regimen and 92.55% (302/322) with the 3-month Rif and I course
      fulfilled the treatment (p=0.024). 2.37% (4/169) and 1.6% (5/313) patients with
      the 6-month I course and 3-month Rif and I course, respectively, withdrew because
      of hepatotoxicity (p=0.33). There were no patients among those who fulfilled the
      treatment in any of the 2 study arms. CONCLUSION: There was a higher adherence
      (statistically significant) and lower hepatotoxicity with the 3-month Rif and I
      regimen. Both regimens showed a full effectivity.

PMID- 20800163
TI  - [Pharmacogenetic studies assessment in clinical research: Four issues, four
      opinions].

PMID- 20800164
TI  - [Never-functioning kidney transplant in a 76-year old woman].

PMID- 20800165
TI  - Biomedical applications of radiation force of ultrasound: historical roots and
      physical basis.
AB  - Radiation force is a universal phenomenon in any wave motion, electromagnetic or
      acoustic. Although acoustic and electromagnetic waves are both characterized by
      time variation of basic quantities, they are also both capable of exerting a
      steady force called radiation force. In 1902, Lord Rayleigh published his classic
      work on the radiation force of sound, introducing the concept of acoustic
      radiation pressure, and some years later, further fundamental contributions to
      the radiation force phenomenon were made by L. Brillouin and P. Langevin. Many of
      the studies discussing radiation force published before 1990 were related to
      techniques for measuring acoustic power of therapeutic devices; also, radiation
      force was one of the factors considered in the search for noncavitational,
      nonthermal mechanisms of ultrasonic bioeffects. A major surge in various
      biomedical applications of acoustic radiation force started in the 1990s and
      continues today. Numerous new applications emerged including manipulation of
      cells in suspension, increasing the sensitivity of biosensors and immunochemical
      tests, assessing viscoelastic properties of fluids and biological tissues,
      elasticity imaging, monitoring ablation of lesions during ablation therapy,
      targeted drug and gene delivery, molecular imaging and acoustical tweezers. We
      briefly present in this review the major milestones in the history of radiation
      force and its biomedical applications. In discussing the physical basis of
      radiation force and its applications, we present basic equations describing the
      relationship of radiation stress with parameters of acoustical fields and with
      the induced motion in the biological media. Momentum and force associated with a
      plane-traveling wave, equations for nonlinear and nonsteady-state acoustic
      streams, radiation stress tensor for solids and biological tissues and radiation
      force acting on particles and microbubbles are considered.

PMID- 20800166
TI  - Investigation of acoustic changes resulting from contrast enhancement in through
      transmission ultrasonic imaging.
AB  - Through-transmitted ultrasonic waves can be used for computed projection imaging
      of the breast. The goal of this research was to analyze the acoustic properties
      changes associated with the propagation of ultrasonic waves through media before
      and after ultrasound contrast agent (UCA) injection and to study the feasibility
      of a new imaging method combining projection imaging and UCA. Two transmission
      techniques were examined: Gaussian pulses and pulse inversion. In the latter,
      three different double inverted pulses were studied: double Gaussian, double
      square and double sine. A computerized automatic ultrasonic scanning system was
      used for imaging. To simulate blood vessels, a phantom, consisting of a latex
      tube through which saline was circulated, was assembled. The phantom was placed
      within the scanner and sets of acoustic projection images were acquired. Then, a
      suspension of the UCA Definitely was added to the saline and a new set of images
      was obtained. The pre and postcontrast images were quantitatively compared in
      terms of amplitude and time-of-flight (TOF). In addition, nonlinearity was
      evaluated by comparing the relative alteration of the positive and negative parts
      of the signal. Statistically significant (p < 0.001) changes in the projection
      images resulting from the UCA injection were observed in wave amplitude (22% +/-
      13%), TOF (7.9 ns +/- 6.3 ns) and nonlinear properties (35% +/- 32% and 56% +/-
      17% for Gausian pulses and pulse inversion, respectively). One in vivo study of a
      female breast is also presented and its preliminary outcomes discussed. Together,
      these results indicate the technical feasibility of the suggested method and its
      potential to detect breast tumors.

PMID- 20800167
TI  - Evaluation of the intraobserver and interobserver reliability of data acquisition
      for three-dimensional power Doppler angiography of the whole placenta at 12 weeks
      gestation.
AB  - The aim of this study was to investigate the intra- and interobserver
      reproducibility of three-dimensional (3-D) power Doppler (3-DPD) data acquisition
      from women at 12 weeks gestation, which were then subsequently measured by a
      single observer. Women with an uncomplicated, viable singleton pregnancy were
      scanned between 12 + 0 and 13 + 6 weeks gestations with a Voluson 730 Expert. 3
      DPD data were acquired of the whole placenta by two observers: the first observer
      captured two datasets and the second a single dataset. Each dataset was analysed
      using VOCAL in the A plane with 9 degree rotation steps. Eighteen low risk women
      were recruited with a total of 54 datasets analysed. The intraclass correlation
      coefficient (ICC) was highest for the vascular indices vascularisation index (VI)
      and vascularisation-flow index (VFI), greater than 0.75. ICC for flow index (FI)
      showed moderate correlation at 0.47 to 0.65. Bland Altman plots showed the most
      precise vascular index to be the FI (-15% to 10% for interobserver agreement).
      There was no bias between datasets. Prospective studies are now required to
      identify if this analysis tool and method is sensitive enough to recognise
      patients with early-onset placental dysfunction.

PMID- 20800168
TI  - Ultrasound measurements of the masseter muscle as predictors of cephalometric
      indices in orthodontics: a pilot study.
AB  - This study investigated the potential of ultrasound measurements of the masseter
      muscle to accurately predict indices normally derived from cephalograms. Masseter
      muscle measurements on 11 adults (22 to 30 y) were made using lateral
      cephalometrics and extended field-of-view ultrasound. The ultrasound technique
      was validated in a simulation pilot study using 12 dry skulls and raw chicken
      breasts. Twenty cephalometric variables were analyzed against four ultrasound
      measurements of the masseter muscle. Highly significant correlations (r = 0.81
      0.85, p = 0.001-0.002) between ultrasound measurements of the masseter muscle and
      cephalometric measurements representing the length of the superficial masseter
      muscle, the length and shape of the mandible and vertical facial proportions were
      demonstrated. Predictive equations from regression analyses were constructed to
      deduce ramus length and shape from the ultrasound measurements. The results
      provide pilot data suggesting that ultrasound is a potential clinical tool for
      sequential evaluation of masseter muscle length in orthodontics and facial muscle
      growth studies.

PMID- 20800169
TI  - Normative cross-sectional area of the C5-C8 nerve roots using ultrasonography.
AB  - This study will define a normal range of values for the cross-sectional area
      (CSA) of the C5-C8 ventral rami in normal subjects and will assess the
      interexaminer reliability of the CSA measurements. We also describe the normal
      sonoanatomy of the C5-C8 ventral rami. Thirty-three normal subjects (20 female)
      were scanned bilaterally. The mean CSA and reference ranges for the C5, C6, C7
      and C8 ventral rami were 7.1 +/- 4.1 mm(2), 10.6 +/- 4.3 mm(2), 12.1 +/- 4.1
      mm(2) and 10.7 +/- 4.8 mm(2), respectively. The intraclass correlation
      coefficient (ICC) demonstrated good reliability with a coefficient of 0.76
      overall, with individual level coefficients at C5, C6, C7 and C8 of 0.69, 0.71,
      0.76 and 0.72, respectively. This is the first study to obtain normative CSA
      measurements of the C5-C8 ventral rami.

PMID- 20800170
TI  - Ultrasound-guided core needle biopsy of cervical lymphadenopathy in patients with
      lymphoma: the clinical efficacy and factors associated with unsuccessful
      diagnosis.
AB  - This study attempts to identify factors that influence the success or failure of
      subclassifying 154 cases of neck lymphoma by ultrasound-guided core needle biopsy
      (UGCNB). Variables including age, gender, nodal size, cutting needle bore, number
      of core tissues obtained, presence of nodal necrosis or infarct, fragmentation of
      the specimens and subclassification of lymphoma were reviewed and statistically
      analyzed to check if they were related to the success of UGCNB. UGCNB was
      successful in subclassifying lymphoma in 138 (89.7%) cases, in diagnosing
      lymphoma in 11 (7.1%) and unsuccessful in diagnosing lymphoma in five (3.2%)
      cases. No complications were encountered. The factors leading to failure in
      subclassification included the presence of composite lymphoma (p = 0.001), nodal
      necrosis or infarct (p = 0.001) and insufficiency or fragmentation of the
      specimens (p < 0.001). UGCNB is a safe and efficient procedure in subclassifying
      lymphoma. It may obviate surgical biopsy in 89.7% of cases.

PMID- 20800171
TI  - Pathological changes on human breast cancer specimens ablated in vitro with high
      intensity focused ultrasound.
AB  - The purpose of this study was to evaluate the pathologic changes of human breast
      cancer specimens ablated with high-intensity focused ultrasound (HIFU) in vitro.
      Twenty specimens of pathologically confirmed breast cancer tissue were ablated
      with ultrasound-guided HIFU. The evaluation methods include histopathologic
      observation using hematoxylin-eosin staining, electron microscopic imaging,
      enzyme histochemical and immunohistochemical examination on tumor antigens.
      Vacuole-like structures in cytoplasm were observed by histopathologic observation
      but there were no significant changes in cell morphology and nucleus karyotype.
      Typical phenomena related to coagulation necrosis were observed in electron
      microscopic studies; the contour of cell structure was still preserved but the
      structures of cell (all kinds of organelles and nucleus) were damaged or
      disappeared. Acid phosphatase and succinate dehydrogenase staining showed that
      tumor cells were inactivated. In immunohistochemical evaluations, estrogen
      receptor, progesterone receptor, cerbB-2 and P53 expression changed from 85%,
      82%, 75% and 80% in nonablation tissue to no expression in ablated tumor tissue,
      respectively. We, therefore, conclude that breast cancer cells appear normal
      contour immediately after ablation with HIFU under light microscopic but they
      were evaluated to be dead by electron microscopic imaging, enzyme histochemical
      and immunohistochemical examinations.

PMID- 20800172
TI  - Multi-modality safety assessment of blood-brain barrier opening using focused
      ultrasound and definity microbubbles: a short-term study.
AB  - As a potentially viable method of brain drug delivery, the safety profile of
      blood-brain barrier (BBB) opening using focused ultrasound (FUS) and ultrasound
      contrast agents (UCA) needs to be established. In this study, we provide a short
      term (30-min or 5-h survival) histological assessment of murine brains undergoing
      FUS-induced BBB opening. Forty-nine mice were intravenously injected with
      Definity microbubbles (0.05 microL/kg) and sonicated under the following
      parameters: frequency of 1.525 MHz, pulse length of 20 ms, pulse repetition
      frequency of 10 Hz, peak rarefactional acoustic pressures of 0.15-0.98 MPa and
      two 30-s sonication intervals with an intermittent 30-s delay. The BBB opening
      threshold was found to be 0.15-0.3 MPa based on fluorescence and magnetic
      resonance imaging of systemically injected tracers. Analysis of three
      histological measures in hematoxylin and eosin-stained sections revealed the
      safest acoustic pressure to be within the range of 0.3-0.46 MPa in all examined
      time periods post sonication. Across different pressure amplitudes, only the
      samples 30 min post opening showed significant difference (p < 0.05) in the
      average number of distinct damaged sites, microvacuolated sites, dark neurons and
      sites with extravasated erythrocytes. Enhanced fluorescence around severed
      microvessels was also noted and found to be associated with the largest tissue
      effects, whereas mildly diffuse BBB opening with uniform fluorescence in the
      parenchyma was associated with no or mild tissue injury. Region-specific areas of
      the sonicated brain (thalamus, hippocampal fissure, dentate gyrus and CA3 area of
      hippocampus) exhibited variation in fluorescence intensity based on the position,
      orientation and size of affected vessels. The results of this short-term
      histological analysis demonstrated the feasibility of a safe FUS-UCA-induced BBB
      opening under a specific set of sonication parameters and provided new insights
      on the mechanism of BBB opening.

PMID- 20800173
TI  - Effects of focused ultrasound and microbubbles on the vascular permeability of
      nanoparticles delivered into mouse tumors.
AB  - Ultrasound sonication with microbubbles (MBs) was evaluated for enhancement of
      the release of nanoparticles from vasculature to tumor tissues. In this study,
      tumor-bearing Balb/c mice were insonicated with focused ultrasound (FUS) in the
      tumors after the injection of MBs (SonoVue) and then lipid-coated quantum dot
      (LQD) nanoparticles (130 +/- 25 nm) were injected through the tail vein. We
      studied the effects of the injected MB dose (0-300 microL/kg), sonication
      duration (0-300 s) and treatment-procedure sequence on the accumulation of
      nanoparticles in the tumors 24 h after the treatment and the time response of the
      accumulation (0.5-24 h). After the treatment, the mice were sacrificed and
      perfused and then the tumor tissues were harvested for quantifying the amount of
      nanoparticles using graphite furnace atomic absorption spectrometry (GF-AAS). The
      results showed that pulsed-FUS sonication with MBs can effectively enhance the
      vascular permeability for LQD nanoparticle delivery into the sonicated tumors. It
      indicates that this technique is promising for a better nanodrug delivery for
      tumor chemotherapy.

PMID- 20800175
TI  - Determining if the relative shear modulus or the inverse of the relative shear
      modulus should be imaged using axial strain ratios on agar phantoms.
AB  - An axial strain image is considered to be an image of a relative shear modulus.
      However, through simulations of focal lesions, it was previously confirmed that
      reconstruction imaging of the 1-D relative shear modulus or its inverse obtained
      from the ratio of the axial strain in the axial direction (i.e., the axial strain
      ratio), with respect to a reference strain, produces larger contrast-to-noise
      ratios (CNRs) than that of the axial strain, although both of the reconstructions
      have smaller relative contrasts than that of the original shear modulus. The
      reference strain is appropriately chosen in the area of a homogeneous
      neighborhood in front of or behind the target by viewing in the B-mode and strain
      images. It has also been confirmed that the evaluations of CNRs of
      reconstructions immediately after strain measurement permit a prediction of which
      reconstructions should be imaged, i.e., a decision can be made without obtaining
      the reconstruction images, but by using the statistical evaluations of the
      measured strains in the focal lesion and in the surrounding region. In this
      study, the feasibility of using this prediction is verified through agar phantom
      experiments using actual measured axial strains obtained with the 2-D cross
      spectrum phase-gradient method. The resulting successful prediction revealed that
      the assumptions of independent stationary and random axial-strain measurement
      errors in the focal lesion and in the surrounding region are appropriate.

PMID- 20800174
TI  - Targeted gene transfection from microbubbles into vascular smooth muscle cells
      using focused, ultrasound-mediated delivery.
AB  - We investigated a method for gene delivery to vascular smooth muscle cells using
      ultrasound triggered delivery of plasmid DNA from electrostatically coupled
      cationic microbubbles. Microbubbles carrying reporter plasmid DNA were
      acoustically ruptured in the vicinity of smooth muscle cells in vitro under a
      range of acoustic pressures (0 to 950 kPa) and pulse durations (0 to 100 cycles).
      No effect on gene transfection or viability was observed from application of
      microbubbles, DNA or ultrasound alone. Microbubbles in combination with
      ultrasound (500-kPa, 1-MHz, 50-cycle bursts at a pulse repetition frequency [PRF]
      of 100 Hz) significantly reduced viability both with DNA (53 +/- 27%) and without
      (19 +/- 8%). Maximal gene transfection ( approximately 1% of cells) occurred
      using 50-cycle, 1-MHz pulses at 300 kPa, which resulted in 40% viability of
      cells. We demonstrated that we can locally deliver DNA to vascular smooth muscle
      cells in vitro using microbubble carriers and focused ultrasound.

PMID- 20800176
TI  - Ultrasound dynamic micro-elastography applied to the viscoelastic
      characterization of soft tissues and arterial walls.
AB  - Quantitative noninvasive methods that provide in vivo assessment of mechanical
      characterization of living tissues, organs and artery walls are of interest
      because information on their viscoelastic properties in the presence of disease
      can affect diagnosis and treatment options. This article proposes the dynamic
      micro-elastography (DME) method to characterize viscoelasticity of small
      homogeneous soft tissues, as well as the adaptation of the method for vascular
      applications [vascular dynamic micro-elastography (VDME)]. The technique is based
      on the generation of relatively high-frequency (240-1100 Hz) monochromatic or
      transient plane shear waves within the medium and the tracking of these waves
      from radio-frequency (RF) echoes acquired at 25 MHz with an ultrasound
      biomicroscope (Vevo 770, Visualsonics). By employing a dedicated shear wave gated
      strategy during signal acquisition, postprocessed RF sequences could achieve a
      very high frame rate (16,000 images per s). The proposed technique successfully
      reconstructed shear wave displacement maps at very high axial (60 mum) and
      lateral (250 mum) spatial resolutions for motions as low as a few mum. An inverse
      problem formulated as a least-square minimization, involving analytical
      simulations (for homogenous and vascular geometries) and experimental
      measurements were performed to retrieve storage (G') and loss (G'') moduli as a
      function of the shearing frequency. Viscoelasticity measurements of agar-gelatin
      materials and of a small rat liver were proven feasible. Results on a very thin
      wall (3 mm thickness) mimicking artery enabled to validate the feasibility and
      the reliability of the vascular inverse problem formulation. Subsequently, the G'
      and G'' of a porcine aorta showed that both parameters are strongly dependent on
      frequency, suggesting that the vascular wall is mechanically governed by complex
      viscoelastic laws.

PMID- 20800177
TI  - A method for arterial diameter change measurements using ultrasonic B-mode data.
AB  - Arterial diameter change is related to distending blood pressure and is used in
      estimation of arterial stiffness parameters. A common technique to track the
      arterial walls is by integration of wall velocities estimated by different
      methods using cross correlation or tissue Doppler. However, because of the high
      pulse repetition frequency and the need for separate pulsing sequences, the B
      mode image quality is affected. We have previously developed a fast algorithm for
      direct measurement of lumen diameter using B-mode images. In this study we have
      improved the technique to be more robust and also implemented measurements of
      diameter change, maximum differential wall velocity and relative diameter change
      of the common carotid artery noninvasively in vivo. The influence of the lateral
      width of the region of interest (ROI; 1 pixel, 0.1 mm, 0.5 mm, 1 mm, 2.5 mm and 5
      mm) was evaluated. Using the optimal lateral width (2.5 mm), the systematic and
      random differences between two consecutive measurements were 21 microm and 105
      microm, respectively, for lumen diameter measurement; -7 microm and 39 microm,
      respectively, for lumen diameter change measurements; -0.2 mm/s and 0.9 mm/s,
      respectively, for maximum relative wall velocity; and -0.2 % and 0.8 %,
      respectively, for measurements of the relative diameter change. The coefficient
      of variation (CV) was 1.9%, 5.2%, 7.9% and 6.0%, respectively. The study
      indicates that the reproducibility is sufficient for in vivo studies when the
      width of the ROI is 1.0 mm or wider.

PMID- 20800178
TI  - Optimization of Doppler echocardiographic velocity measurements using an
      automatic contour detection method.
AB  - Intra- and interobserver variability in Doppler echocardiographic velocity
      measurements (DEVM) is a significant issue. Indeed, imprecisions of DEVM can lead
      to diagnostic errors, particularly in the quantification of the severity of heart
      valve dysfunctions. To reduce the variability and rapidity of DEVM, we have
      developed an automatic method of Doppler velocity wave contour detection, based
      on active contour models. To validate our new method, results obtained with this
      method were compared with those obtained manually by two experienced
      echocardiographers on Doppler echocardiographic images of left ventricular
      outflow tract and transvalvular flow velocity signals recorded in 30 patients
      with aortic or mitral stenosis, 20 with normal sinus rhythm and 10 with atrial
      fibrillation. We focused on the three essential variables that are measured
      routinely using Doppler echocardiography in the clinical setting: the maximum
      velocity (Vmax), the mean velocity (Vmean) and the velocity-time integral (VTI).
      Comparison between the two methods has shown a very good agreement. A small bias
      value was found between the two methods (between -3.9% and 0.5% for Vmax, between
      -4.6% and -1.4% for Vmean and between -3.6% and 4.4% for VTI). Moreover, the
      computation time was short, approximately 5 s. This new method applied to DEVM
      could, therefore, provide a useful tool to eliminate the intra- and interobserver
      variabilities associated with DEVM and thereby to improve the accuracy of the
      diagnosis of cardiovascular disease. This automatic method could also allow the
      echocardiographer to realize these measurements within a much shorter period of
      time compared with the standard manual tracing method. From a practical point of
      view, the model developed can be easily implemented in a standard
      echocardiographic system.

PMID- 20800179
TI  - Computer aided diagnosis of parotid gland lesions using ultrasonic multi-feature
      tissue characterization.
AB  - In this article, an ultrasound based system for computer aided characterization
      of biologic tissue and its application to differential diagnosis of parotid gland
      lesions is proposed. Aiming at an automated differentiation between malignant and
      benign cases, the system is based on a supervised classification using tissue
      describing features derived from ultrasound radio-frequency (RF) echo signals and
      image data. Standard diagnostic ultrasound equipment was employed to acquire
      ultrasound RF echo data from parotid glands of 138 patients. Lesions were
      manually demarcated as regions-of-interest (ROIs) in the B-mode images. Spectral
      ultrasound backscatter and attenuation parameters are estimated from diffraction
      corrected RF data, yielding spatially resolved parameter images. Histogram based
      statistical measures derived from the parameters distributions inside the ROI are
      used as tissue describing features. In addition, texture features and shape
      descriptors are extracted from demodulated ultrasound image data. The features
      are processed by a maximum likelihood classifier. An optimal set of 10 features
      was chosen by a sequential forward selection algorithm. The classifier's
      performance is evaluated using total cross validation and receiver operating
      characteristic (ROC) analysis. As a reference method, postoperative
      pathohistologic analysis was conducted and proved malignancy or prospective
      malignancy in 51 patients. The classification using the proposed system yielded
      an area under the ROC curve of 0.91, proving significant potential for
      differentiating between malignant and benign parotid gland lesions.

PMID- 20800180
TI  - Amplitude-modulation chirp imaging for contrast detection.
AB  - We propose an amplitude-modulation chirp imaging method for contrast detection
      with high-frequency ultrasound. Our proposed method detects microbubbles by
      extracting and then selectively compressing the component of the backscattered
      chirp signal modulated by changes in the radii of microbubbles at their resonance
      frequency. Microbubbles are sonicated simultaneously with a narrowband, low
      frequency pumping signal at their resonance frequency and a wideband, high
      frequency imaging chirp signal. Changes in the radii of the resonant microbubbles
      result in periodic changes in their acoustic cross section that modulate the
      amplitude of the backscattered imaging chirp signal, forming pumping and imaging
      frequency sum-and-difference chirp terms. The frequency-sum or -difference chirp
      component is then extracted by a bandpass filter (BPF). Because a long imaging
      pulse duration is required to obtain a sufficient modulation depth on the chirp
      for contrast detection and to facilitate frequency-sum-and-difference signal
      extraction with the BPF, a chirp with a longer-than-usual waveform is used so
      pulse compression of the extracted chirp signal can then be performed to maintain
      the axial resolution, and even further improve the signal-to-noise ratio and
      contrast-to-tissue ratio. Experiments performed on flow phantoms with and without
      a speckle-generating background were performed to demonstrate the efficacy of the
      proposed technique. These results indicate that our proposed method can
      potentially provide high-resolution contrast detection in the microvasculature.

PMID- 20800181
TI  - An increase in cellular size variance contributes to the increase in ultrasound
      backscatter during cell death.
AB  - This study aims to explain the contribution of changes in cellular size variance
      (CSV) to increases in ultrasound-integrated backscatter (UIB) measured from cell
      samples undergoing cell death. A Monte Carlo algorithm was used to compare
      simulations of 2D distributions of cells, uniform (CSV = 0) versus heterogeneous
      (CSV > 0) and the same mean cellular size (M ). UIB increased in arrangements
      with heterogeneous cellular sizes from 3.6dB (M = 20 mum, CSV = 0 microm/CSV = 18
      microm) to 5.6 dB (M =10 microm, CSV = 0 microm/CSV = 8 microm). Experimentally,
      UIB (10 to 30 MHz) was measured from cell samples of four tumor cell lines viable
      and undergoing cell death after radiotherapy and chemotherapy treatment. An
      increase of 3.8-7.5 dB (p < 0.001) in UIB was measured from three cell lines. No
      increase in UIB was measured from one cell line. An increase in CSV was found for
      all cell samples after cell death. The results suggest that an increase in CSV
      could have a significant contribution to the increases measured in UIB after cell
      death in cell samples exposed to anticancer therapies.

PMID- 20800182
TI  - [Genetic barrier to antiretroviral drug-resistance. Focus on raltegravir, the
      first integrase inhibitor].
AB  - The genetic barrier for the antiretroviral describes the ability to select
      resistant viruses to this antiretroviral when the viral replication is not
      controlled. This includes combining several concepts: (1) the number of
      nucleotide changes required for a resistance mutation, (2) the impact of this
      mutation on the level of susceptibility to antiretroviral (3) the impact of this
      mutation on viral replication capacity; all theses conditions influencing the
      level of resistant variants. The antiretroviral concentration impact also the
      emergence of resistance. Finally, combine with other molecules, the selection of
      resistance mutations ton an antiretroviral may differ from one treatment to
      another. It is recognized that the genetic barrier to lamivudine/emtricitabine,
      efavirenz and nevirapine is low, and is intermediate for nucleoside such as
      zidovudine and tenofovir. However, ritonavir boosted protease inhibitor with high
      plasma concentration have a high genetic barrier. For integrase inhibitors such
      as raltegravir, the emergence of resistance is certainly faster than the
      ritonavir boosted protease inhibitors, but seems slower and less systematic than
      for efavirenz or lamivudine. Many factors could influence the raltegravir
      resistance such as the level of viral load and replication duration, genetic
      polymorphism of HIV (integrase gene and other, viral subtype) and the plasma
      and/or intra- cellular raltegravir concentration.

PMID- 20800183
TI  - Mouse models of neurological disorders. Preface.

PMID- 20800184
TI  - Feasibility and safety of a new robotic thyroidectomy through a gasless,
      transaxillary single-incision approach.

PMID- 20800185
TI  - Cognitive functioning, retirement status, and age: results from the Cognitive
      Changes and Retirement among Senior Surgeons study.
AB  - BACKGROUND: Accurate assessment of cognitive functioning is an important step in
      understanding how to better evaluate both clinical and cognitive competence in
      practicing surgeons. As part of the Cognitive Changes and Retirement among Senior
      Surgeons study, we examined the objective cognitive functioning of senior
      surgeons in relation to retirement status and age. STUDY DESIGN: Computerized
      cognitive tasks measuring visual sustained attention, reaction time, and visual
      learning and memory were administered to both practicing and retired surgeons at
      annual meetings of the American College of Surgeons. Data from 168 senior
      surgeons aged 60 and older were compared with data from 126 younger surgeons aged
      45 to 59, with performance below 1.5 standard deviations or more indicating a
      significant difference between the groups. RESULTS: Sixty-one percent of
      practicing senior surgeons performed within the range of the younger surgeons on
      all cognitive tasks. Seventy-eight percent of practicing senior surgeons aged 60
      to 64 performed within the range of the younger surgeons on all tasks compared
      with 38% of practicing senior surgeons aged 70 and older. Forty-five percent of
      retired senior surgeons performed within the range of the younger surgeons on all
      tasks. No senior surgeon performed below the younger surgeons on all 3 tasks.
      CONCLUSIONS: The majority of practicing senior surgeons performed at or near the
      level of their younger peers on all cognitive tasks, as did almost half of the
      retired senior surgeons. This suggests that older age does not inevitably
      preclude cognitive proficiency. The variability in cognitive performance across
      age groups and retirement status suggests the need for formal measures of
      objective cognitive functioning to help surgeons detect changes in cognitive
      performance and aid in their decisions to retire.

PMID- 20800186
TI  - Electronic synoptic operative reporting: assessing the reliability and
      completeness of synoptic reports for pancreatic resection.
AB  - BACKGROUND: Electronic synoptic operative reports (E-SORs) have replaced dictated
      reports at many institutions, but whether E-SORs adequately document the
      components and findings of an operation has received limited study. This study
      assessed the reliability and completeness of E-SORs for pancreatic surgery
      developed at our institution. STUDY DESIGN: An attending surgeon and surgical
      fellow prospectively and independently completed an E-SOR after each of 112 major
      pancreatic resections (78 proximal, 29 distal, and 5 central) over a 10-month
      period (September 2008 to June 2009). Reliability was assessed by calculating the
      interobserver agreement between attending physician and fellow reports.
      Completeness was assessed by comparing E-SORs to a case-matched (surgeon and
      procedure) historical control of dictated reports, using a 39-item checklist
      developed through an internal and external query of 13 high-volume pancreatic
      surgeons. RESULTS: Interobserver agreement between attending and fellow was
      moderate to very good for individual categorical E-SOR items (kappa = 0.65 to
      1.00, p < 0.001 for all items). Compared with dictated reports, E-SORs had
      significantly higher completeness checklist scores (mean 88.8 +/- 5.4 vs 59.6 +/-
      9.2 [maximum possible score, 100], p < 0.01) and were available in patients'
      electronic records in a significantly shorter interval of time (median 0.5 vs 5.8
      days from case end, p < 0.01). The mean time taken to complete E-SORs was 4.0 +/-
      1.6 minutes per case. CONCLUSIONS: E-SORs for pancreatic surgery are reliable,
      complete in data collected, and rapidly available, all of which support their
      clinical implementation. The inherent strengths of E-SORs offer real promise of a
      new standard for operative reporting and health communication.

PMID- 20800187
TI  - Prosthetic graft reconstruction after portal vein resection in
      pancreaticoduodenectomy: a multicenter analysis.
AB  - BACKGROUND: Use of prosthetic grafts for reconstruction after portal vein (PV)
      resection during pancreaticoduodenectomy is controversial. We examined outcomes
      in patients who underwent vein reconstruction using polytetrafluoroethylene
      (PTFE). STUDY DESIGN: Review of prospectively maintained databases at 3 centers
      identified all patients who underwent pancreaticoduodenectomy (PD) with vein
      resection and reconstruction using PTFE grafts between 1994 and 2009. Patient,
      operative, and outcomes variables were studied. Graft patency and survival were
      assessed using the Kaplan-Meier technique. RESULTS: Thirty-three patients
      underwent segmental vein resection with interposition PTFE graft reconstruction.
      Median age was 67 years; median Eastern Cooperative Oncology Group score was 1.
      Most operations were performed for pancreatic adenocarcinoma (n = 28, 85%); 96%
      were T3 lesions or greater. Standard PD was performed in 12 (36%) patients,
      pylorus-preservation in 17 (52%), and total pancreatectomy in 4 (12%). Combined
      resection of portal and superior mesenteric veins (SMV) was required in 49%, with
      resection isolated to PV in 12% and SMV in 39%. Splenic vein ligation was
      necessary in 30%. Median graft diameter was 12 mm (range 8 to 20 mm), with the
      majority being ring-enforced (73%). Median operative and vascular clamp times
      were 463 and 41 minutes, respectively, with median blood loss of 1,500 mL. The
      negative margin rate was 64%. Overall morbidity rate was 46%, and 30-day
      mortality was 6%. No patients developed irreversible hepatic necrosis or graft
      infection. Pancreatic fistulas occurred in 3 (9.1%). With mean follow-up of 14
      months, overall graft patency was 76%. Estimated median duration of graft patency
      was 21 months. Median survival was 12 months for pancreatic adenocarcinoma.
      CONCLUSIONS: With careful patient selection, PTFE graft reconstruction of
      resected PV/SMV during pancreaticoduodenectomy is possible with minimal risk of
      hepatic necrosis or graft infection. Comparison studies to primary anastomosis
      and autologous vein reconstruction are necessary.

PMID- 20800188
TI  - Hospital characteristics associated with failure to rescue from complications
      after pancreatectomy.
AB  - BACKGROUND: Failure to rescue (ie, mortality after a major complication) has
      recently been demonstrated as a mechanism underlying differences between high and
      low mortality hospitals. In this study, we sought to better understand the
      hospital characteristics that may explain failure to rescue. STUDY DESIGN: Using
      data from the 2000 to 2006 Nationwide Inpatient Sample and the American Hospital
      Association annual survey, we evaluated the effect of 5 hospital level
      characteristics on failure to rescue (FTR) rates. Using multivariate logistic
      regression models, we determined the relative contribution of each of these
      factors to the FTR rates at the lowest and highest mortality hospitals. RESULTS:
      Failure to rescue varied 6-fold across hospitals (6.4% in very low mortality
      hospitals vs 40.0% in very high mortality hospitals, p < 0.001). Several hospital
      characteristics were significantly associated with lower FTR: teaching status
      (odds ratio [OR] 0.66, 95% CI 0.53 to 0.82), hospital size greater than 200 beds
      (OR 0.65, 95% CI 0.48 to 0.87), average daily census greater than 50% capacity
      (OR 0.56, 95%CI 0.32 to 0.98), increased nurse-to-patient ratios (OR 0.94, 95% CI
      0.89 to 0.99), and high hospital technology (OR 0.65, 95% CI 0.52 to 0.81).
      Including all hospital characteristics into a multivariate model results in a 36%
      reduction in the odds of FTR between very high and very low mortality hospitals
      (OR 6.6, 95% CI 3.7 to 11.9). CONCLUSIONS: Several hospital characteristics are
      associated with FTR from major complications. However, a large portion of what
      makes some hospitals better than others at rescuing patients remains unexplained.
      Future research should focus on hospital cultures and attitudes that may
      contribute to the timely recognition and effective management of major
      complications.

PMID- 20800189
TI  - Online spaced education generates transfer and improves long-term retention of
      diagnostic skills: a randomized controlled trial.
AB  - BACKGROUND: Retention of learning from surgical training is often limited,
      especially if the knowledge and skills are used infrequently. Using
      histopathology diagnostic skills as an experimental system, we compared knowledge
      transfer and retention between bolus Web-based teaching (WBT) modules and online
      spaced education, a novel email-based method of online education founded on the
      spacing effect. STUDY DESIGN: All US urology residents were eligible to
      participate. Enrollees were randomized to 1 of 2 cohorts. Cohort 1 residents
      received 3 cycles/repetitions of spaced education on prostate-testis
      histopathology (weeks 1 to 16) and 3 WBT modules on bladder-kidney (weeks 14 to
      16). Cohort 2 residents received 3 cycles of spaced education on bladder-kidney
      (weeks 1 to 16) and 3 WBT modules on prostate-testis (weeks 14 to 16). Each daily
      spaced education email presented a clinical scenario with histopathology image
      and asked for a diagnosis. Participants received immediate feedback after
      submitting their answers. Each cycle/repetition was 4 weeks long and consisted of
      20 questions with unique images. WBT used the identical content and delivery
      system, with questions aggregated into three 20-question modules. Long-term
      retention of all 4 topics was assessed during weeks 18 to 45. RESULTS: Seven
      hundred and twenty-four urology residents enrolled. Spaced education and WBT were
      completed by 77% and 66% of residents, respectively. Spaced education and WBT
      generated mean long-term score increases of 15.2% (SD 15.3%) and 3.4% (SD 16.3%),
      respectively (p < 0.01). Spaced education increased long-term learning efficiency
      4-fold. CONCLUSIONS: Online spaced education generates transfer of histopathology
      diagnostic skills and substantially improves their long-term retention.
      Additional research is needed to determine how spaced education can optimize
      learning, transfer, and retention of surgical skills.

PMID- 20800190
TI  - Effect of pre-existing medical conditions on in-hospital mortality: analysis of
      20,257 trauma patients in Japan.
AB  - BACKGROUND: The average life expectancy of Japanese individuals is the longest in
      the world. The mortality rate from injury is increasing among older people. There
      have been no detailed reports on the relationship between pre-existing medical
      conditions (PMCs) and mortality from trauma among elderly people in Japan. STUDY
      DESIGN: We conducted a retrospective analysis using 20,257 cases recorded in the
      Japan Trauma Data Bank from 2004 to 2007. The subjects were 11,590 hospital
      inpatients (57.2%) 16 years of age or older. A logistic regression analysis was
      conducted for the relation between 23 PMCs and in-hospital mortality. RESULTS:
      Overall in-hospital mortality was 10.8%, and for people 75 years of age and
      older, was 17.7%. The incidence of PMC was 4,752 (41.0%). Patients with PMCs of
      cirrhosis, active cancer, chronic obstructive pulmonary disease, hematologic
      disorders, anticoagulation drugs, dementia or mental retardation, or other
      conditions had higher in-hospital mortality. The existence of a single PMC did
      not increase mortality, but with 2 or more PMCs, mortality significantly
      increased. The existence of 2 or more PMCs in the 50- to 74-year-old age group
      and in the minor injury group strongly affected the odds ratio for mortality.
      CONCLUSIONS: The existence of certain PMCs or of 2 or more PMCs increases in
      hospital mortality from injury. This effect is particularly conspicuous in middle
      aged patients and people with minor injuries, but was not found to be a problem
      among elderly people. The increased mortality from injury in elderly people in
      Japan is therefore not affected by the existence of PMCs.

PMID- 20800191
TI  - Detection of postoperative respiratory failure: how predictive is the Agency for
      Healthcare Research and Quality's Patient Safety Indicator?
AB  - BACKGROUND: Patient Safety Indicator (PSI) 11, or postoperative respiratory
      failure, was developed by the US Agency for Healthcare Research and Quality to
      detect incident cases of respiratory failure after elective operations through
      use of ICD-9-CM diagnosis and procedure codes. We sought to determine the
      positive predictive value (PPV) of this indicator. STUDY DESIGN: We conducted a
      retrospective cross-sectional study, sampling consecutive cases that met PSI 11
      criteria from 18 geographically diverse academic medical centers on or before
      June 30, 2007. Trained abstractors from each center reviewed medical records
      using a standard instrument. We assessed the PPV of the indicator (with 95% CI
      adjusted for clustering within centers) and conducted descriptive analyses of the
      cases. RESULTS: Of 609 cases that met PSI 11 criteria, 551 (90.5%; 95% CI, 86.5
      94.4%) satisfied the technical criteria of the indicator and 507 (83.2%; 95% CI,
      77.2-89.3%) represented true cases of postoperative respiratory failure from a
      clinical standpoint. The most frequent reasons for being falsely positive were
      nonelective hospitalization, prolonged intubation for airway protection, and
      insufficient evidence to support a diagnosis of acute respiratory failure. Fifty
      percent of true-positive cases involved substantial baseline comorbidities, and
      23% resulted in death. CONCLUSIONS: Although PSI 11 predicts true postoperative
      respiratory failure with relatively high frequency, the indicator does not limit
      detection to preventable cases. The PPV of PSI 11 might be increased by excluding
      cases with a principal diagnosis suggestive of a nonelective hospitalization and
      those with head or neck procedures. Removing the diagnosis code criterion from
      the indicator might also increase PPV, but would decrease the number of true
      positive cases detected by 20%.

PMID- 20800192
TI  - Examination of the impact of airbags on renal injury using a national database.
AB  - BACKGROUND: Little is known about preventative measures to lessen solid organ
      injury in motor vehicle collisions (MVCs). To evaluate the efficacy of airbags in
      reducing renal injuries in MVC, we analyzed renal injury rates in vehicles with
      and without airbags using the Crash Injury Research and Engineering Network
      (CIREN) database. STUDY DESIGN: The CIREN database was queried for MVC and renal
      injury from 1996 to September 2008. CIREN is weighted toward late model vehicles
      and selects more severely injured patients. Search fields were primary direction
      of force (PDOF), presence of airbags, and location of airbags (steering wheel,
      instrument panel, seat back, door panel, and roof-side curtain). Abdominal
      Abbreviated Injury Score was converted to AAST renal injury grade. Renal injury
      rates were compared between vehicles with and without frontal and side airbags.
      RESULTS: We reviewed 2,864 records and identified 139 renal injuries (28.9% AAST
      grade III to V). In MVCs with renal injuries, frontal impact was 54.7% of total
      (n = 76) and side impact was 45.3% of total (n = 63). Most occupants in frontal
      impact MVCs had exposure to a steering wheel airbag (74.9%); 16.6% had an
      instrument panel (passenger) airbags. In side impact MVCs, 32.2% of occupants had
      a side airbag. Compared with the non-airbags cohort, frontal airbags and side
      airbags were associated with a 45.3% and 52.8% reduction in renal injury,
      respectively. CONCLUSIONS: Passengers in automobiles with frontal and side
      airbags have a reduced rate of renal injury compared with those without airbags.
      Our data support further study of the role of airbags in reducing renal injury
      after MVC.

PMID- 20800193
TI  - Prospective randomized trial of accelerated re-epithelization of skin graft donor
      sites using extracorporeal shock wave therapy.
AB  - BACKGROUND: Extracorporeal shock wave therapy may enhance revascularization and
      repair of healing soft tissue. METHODS: Between January 2006, and September 2007,
      28 patients with acute traumatic wounds and burns requiring skin grafting were
      randomly assigned in a 1:1 fashion to receive standard topical therapy
      (nonadherent silicone mesh [Mepitel, Molnlycke Health Care] and antiseptic gel
      [polyhexanide/octenidine]) to graft donor sites with (n = 13) or without (n = 15)
      defocused extracorporeal shock wave therapy (ESWT, 100 impulses/cm(2) at 0.1
      mJ/mm(2)) applied once to the donor site, immediately after skin harvest. The
      randomization sequence was computer generated, and the patients were blinded to
      treatment allocation. The primary endpoint was time to complete donor site
      epithelialization and was determined by an independent blinded observer. RESULTS:
      Statistical tests indicated no unbalanced distribution of subject characteristics
      across the two study groups. Mean times to complete graft donor site
      epithelialization for patients who did and did not undergo ESWT were 13.9 +/- 2.0
      days and 16.7 +/- 2.0 days, respectively (p = 0.0001). CONCLUSIONS: For centers
      that apply nonadherent gauze dressings and topical antiseptics to skin graft
      donor sites, application of a single defocused shock wave treatment immediately
      after skin graft harvest can significantly accelerate donor site
      epithelialization.

PMID- 20800194
TI  - Comparison of cross-linked and non-cross-linked porcine acellular dermal matrices
      for ventral hernia repair.
AB  - BACKGROUND: Porcine acellular dermal matrices (PADMs) have been used clinically
      for abdominal wall repair. The newer non-cross-linked PADMs, however, have not
      been directly compared with cross-linked PADMs. We hypothesized that chemical
      cross-linking affects the biologic host response to PADMs used to repair ventral
      hernias. STUDY DESIGN: Fifty-eight guinea pigs underwent inlay repair of
      surgically created ventral hernias using cross-linked or non-cross-linked PADM.
      After animals were sacrificed at 1, 2, or 4 weeks, the tenacity of and surface
      area involved by adhesions to the repair sites were measured. Sections of the
      repair sites, including the bioprosthesis-musculofascia interface, underwent
      histologic analysis of cellular and vascular infiltration plus mechanical
      testing. RESULTS: Compared with cross-linked PADM repairs, non-cross-linked PADM
      repairs had a significantly lower mean tenacity grade of adhesions at all
      timepoints and mean adhesion surface area at week 1. Mean cellular and vascular
      densities were significantly higher in non-cross-linked PADM at all timepoints.
      Cells and vessels readily infiltrated into the center of non-cross-linked PADM,
      but encapsulated cross-linked PADM, with a paucity of penetration into it.
      Mechanical properties were similar for the two PADMs (in isolation) at all
      timepoints; however, at the bioprosthesis-musculofascia interface, both elastic
      modulus and ultimate tensile strength were significantly higher at weeks 1 and 2
      for non-cross-linked PADM. CONCLUSIONS: Non-cross-linked PADM is rapidly
      infiltrated with host cells and vessels; cross-linked PADM becomes encapsulated.
      Non-cross-linked PADM causes weaker adhesions to repair sites while increasing
      the mechanical strength of the bioprosthesis-musculofascia interface at early
      timepoints. Non-cross-linked PADM may have early clinical advantages over cross
      linked PADM for bioprosthetic abdominal wall reconstruction.

PMID- 20800195
TI  - Laparoscopic versus open 2-stage ileal pouch: laparoscopic approach allows for
      faster restoration of intestinal continuity.
AB  - BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA)
      is the treatment of choice for patients with ulcerative colitis and familial
      adenomatous. This study examined the impact of the surgical approach
      (laparoscopic versus open) to IPAA on short-term outcomes and time to ileostomy
      closure in 2-stage restorative proctocolectomies. STUDY DESIGN: A retrospective
      review was performed on a prospectively maintained database at Washington
      University School of Medicine for patients undergoing elective 2-stage
      restorative proctocolectomy and IPAA from April of 1999 through July of 2008.
      Outcomes for patients were analyzed according to laparoscopic versus open
      technique. RESULTS: A total of 124 patients (55 laparoscopy, 69 open) were
      included in this study. Laparoscopic IPAA took, on average, 79.2 minutes longer
      to complete than open IPAA (p < 0.0001) and required significantly more
      intravenous fluid administration (p = 0.0004). There was no significant
      difference between laparoscopic and open IPAA with respect to estimated blood
      loss, blood transfusions, postoperative narcotic usage, return of bowel function,
      length of stay, and hospital readmission rates. Total complications were not
      statistically significant between the 2 groups. Patients in the laparoscopic IPAA
      group underwent ileostomy closure an average of 24.1 days sooner than patients in
      the open group (p = 0.045). Multivariate analysis revealed that surgical approach
      (p = 0.018) and length of stay (p = 0.004) were associated with faster time to
      closure of loop ileostomy. CONCLUSIONS: Laparoscopic IPAA is safe, with
      postoperative morbidity comparable with open IPAA. Laparoscopic IPAA can lead to
      faster recovery and result in faster progression to restoration of intestinal
      continuity in patients undergoing 2-stage restorative proctocolectomy.

PMID- 20800197
TI  - Impact of extended spectrum beta-lactamase producing Klebsiella pneumoniae
      infections in severely burned patients.
AB  - BACKGROUND: Significantly higher mortality has been demonstrated in patients who
      suffer severe burns complicated by Klebsiella pneumoniae bacteremia. The specific
      virulence mechanisms associated with this organism in this population are
      unclear. STUDY DESIGN: Our study assessed the impact of the mechanism of
      antibiotic resistance, strain clonality, and other host factors on morbidity and
      mortality. All patients with thermal burns infected with K pneumoniae between
      January 1, 2004 and July 1, 2008 were included in the analysis. RESULTS: Ninety
      one patients had 111 episodes of K pneumoniae infections, with 59 isolates among
      the 91 patients producing extended spectrum beta-lactamase (ESBL). Patients with
      ESBL-producing strains were slightly younger, had higher Injury Severity Scores
      (ISS), and higher percent full thickness burns. Those who survived to discharge
      were younger (p < 0.001), had less burned surface area (p = 0.013), had fewer
      ventilator days (p = 0.016), and fewer infections with ESBL-producing isolates (p
      = 0.042). Logistic regression revealed that an infection with ESBL-producing K
      pneumoniae during the hospital stay was the factor most predictive of death, with
      a nearly 4-fold increased odds of dying. However, survival duration analysis of
      the population with and without ESBL-producing K pneumoniae using Kaplan-Meier
      technique showed no significant difference in the populations. Cox regression
      proportional hazards model revealed that only age (p = 0.01) and ventilator days
      (p < or = 0.01) were associated with time to death. No specific clonality of the
      strains tested or ESBL production resistance genes were associated with mortality
      or ESBL production. CONCLUSIONS: These results suggest that infections caused by
      ESBL-producing K pneumoniae are predictive of death when occurring in an older,
      more badly burned population.

PMID- 20800196
TI  - Consequences of adrenal venous sampling in primary hyperaldosteronism and
      predictors of unilateral adrenal disease.
AB  - BACKGROUND: In patients with primary hyperaldosteronism, distinguishing between
      unilateral and bilateral adrenal hypersecretion is critical in assessing
      treatment options. Adrenal venous sampling (AVS) has been advocated by some to be
      the gold standard for localization of the responsible lesion, but there remains a
      lack of consensus for the criteria and the standardization of technique. STUDY
      DESIGN: We performed a retrospective study of 114 patients with a biochemical
      diagnosis of primary hyperaldosteronism who all underwent CT scan and AVS before
      and after corticotropin (ACTH) stimulation. Univariate and multivariate analyses
      were performed to determine what factors were associated with AVS lateralization,
      and which AVS values were the most accurate criteria for lateralization. RESULTS:
      Eighty-five patients underwent surgery at our institution for unilateral
      hyperaldosteronism. Of the 57 patients who demonstrated unilateral abnormalities
      on CT, AVS localized to the contralateral side in 5 patients and revealed
      bilateral hyperplasia in 6 patients. Of the 52 patients who showed bilateral
      disease on CT scan, 43 lateralized with AVS. The most accurate criterion on AVS
      for lateralization was the post-ACTH stimulation value. Factors associated with
      AVS lateralization included a low renin value, high plasma aldosterone-to plasma
      renin ratio, and adrenal mass > or = 3 cm on CT scan. CONCLUSIONS: Because 50% of
      patients would have been inappropriately managed based on CT scan findings,
      patients with biochemical evidence of primary hyperaldosteronism and considering
      adrenalectomy should have AVS. The most accurate measurement for AVS
      lateralization was the post-ACTH stimulation value. Although several factors
      predict successful AVS lateralization, none are accurate enough to perform AVS
      selectively.

PMID- 20800198
TI  - Live transference of surgical subspecialty skills using telerobotic proctoring to
      remote general surgeons.
AB  - BACKGROUND: Certain clinical environments, including military field hospitals or
      rural medical centers, lack readily available surgical subspecialists. We
      hypothesized that telementoring by a surgical subspecialist using a robotic
      platform is feasible and can convey subspecialty knowledge and skill to a
      remotely located general surgeon. STUDY DESIGN: Eight general surgery residents
      evaluated the effect of remote surgical telementoring by performing 3 operative
      procedures, first unproctored and then again when teleproctored by a surgical
      subspecialist. The clinical scenarios consisted of a penetrating right
      ventricular injury requiring suture repair, an open tibial fracture requiring
      external fixation, and a traumatic subdural hematoma requiring craniectomy. A
      robotic platform consisting of a pan-and-tilt camera with laser pointer attached
      to an overhead surgical light with integrated audio allowed surgical
      subspecialists the ability to remotely teleproctor residents. Performance was
      evaluated using an Operative Performance Scale. Satisfaction surveys were given
      after performing the scenario unproctored and again after proctoring. RESULTS:
      Overall mean performance scores were superior in all scenarios when residents
      were proctored than when they were not (4.30 +/- 0.25 versus 2.43 +/- 0.20; p <
      0.001). Mean performance scores for individual metrics, including tissue
      handling, instrument handling, speed of completion, and knowledge of anatomy,
      were all superior when residents were proctored (p < 0.001). Satisfaction surveys
      showed greater satisfaction and comfort among residents when proctored. Proctored
      residents believed the robotic platform facilitated learning and would be
      feasible if used clinically. CONCLUSIONS: This study supports the use of surgical
      teleproctoring in guiding remote general surgeons by a surgical subspecialist in
      the care of a wounded patient in need of an emergency subspecialty operation.

PMID- 20800200
TI  - Dr Gross's assistants in The Gross Clinic.

PMID- 20800201
TI  - Meta-analysis comparing healing by primary closure and open healing after surgery
      for pilonidal sinus.

PMID- 20800202
TI  - Missing data analyses.

PMID- 20800199
TI  - Laparoscopic surgery for cancer: a systematic review and a way forward.

PMID- 20800204
TI  - Primary hyperparathyroidism from parathyroid microadenoma.

PMID- 20800207
TI  - The fight against some formidable fungal foes.

PMID- 20800208
TI  - Feline hyperthyroidism: potential relationship with iodine supplement
      requirements of commercial cat foods.
AB  - ARTICLE RATIONALE: Since the late 1970s, there has been a significant increase in
      the prevalence of feline hyperthyroidism (FH). It is now recognized worldwide as
      the most common endocrinopathy of older cats, resembling toxic nodular goiter of
      older humans in iodine-deficient areas. The purpose of this article is to
      identify the potential for iodine concentrations in the diet to contribute to the
      etiology of FH. HISTORICAL CONTEXT: Iodine concentrations of commercial cat foods
      vary widely. A review of historical iodine recommendations revealed that the
      units of iodine supplementation changed in the 1970s. Given this change, foods
      minimally supplemented since the late 1970s would have been iodine deficient for
      most cats. PRACTICAL RELEVANCE: Iodine supplementation of commercial cat foods
      should be evaluated in the light of the iodine recommendations revised in 2006.
      Foods may remain deficient in iodine if supplemented at the minimum recommended
      concentration, possibly contributing to the development of FH.

PMID- 20800209
TI  - Feline asthma: what's new and where might clinical practice be heading?
AB  - PRACTICAL RELEVANCE: Feline bronchial asthma is one of the most commonly
      diagnosed respiratory conditions of cats. Clinical signs range from intermittent
      wheezing and coughing, which can compromise quality of life, to episodes of
      severe dyspnea that can be life-threatening. CLINICAL CHALLENGES: Feline asthma
      can be easily disregarded as a simplistic condition. However, much about its
      pathophysiology remains obscure. There is no gold standard method of diagnosis,
      and current approaches are associated with various limitations. Also, feline
      asthma is typically treated with long-term glucocorticoid therapy, which can have
      significant consequences. AUDIENCE: Because of its prevalence, general
      practitioners encounter asthma regularly. Refractory cases are often managed by
      veterinary internists and pulmonologists. PATIENT GROUP: Asthma can be diagnosed
      in cats of any age but is usually seen in young to middle-aged adults (mean 4
      years, range 1-15 years). There is no sex predilection, but the Siamese breed
      appears to be overrepresented. EVIDENCE BASE: While the standard clinical
      approach to feline asthma has changed little in recent years, new research has
      provided greater insight into many aspects of this complex disease and new
      strategies are being studied. This article reviews the current literature in
      order to raise awareness of how advances in the understanding of the
      pathophysiology, diagnosis and treatment of feline asthma may be determining the
      future direction of clinical practice.

PMID- 20800210
TI  - Pleural effusion in the cat: a practical approach to determining aetiology.
AB  - PRACTICAL RELEVANCE: Diverse disease processes result in sufficient fluid
      accumulation within the pleural space to cause respiratory compromise.
      Determining the underlying aetiology is key to appropriate management. This
      review outlines a practical approach to cases of pleural effusion, focusing on
      early recognition and confirmation of pleural space disease, stabilisation of the
      patient and logical diagnostic investigation. It emphasises the importance of a
      holistic approach, incorporating fluid analysis with other clinical data to
      determine the underlying aetiology. CLINICAL CHALLENGES: Cats with pleural
      effusion often have severe respiratory compromise at presentation. Careful
      handling and prompt and adequate stabilisation, incorporating supplemental oxygen
      and therapeutic thoracocentesis, is essential to avoid respiratory failure. The
      typical, stepwise approach to the case must be adapted and the clinician may have
      to proceed, at least initially, without the luxury of information gained from a
      full history and physical examination. The challenge is to juggle stabilisation,
      localisation and confirmation of pleural effusion, owner communication and
      minimally invasive examination while remaining vigilant for clues that allow
      ranking of the differentials to formulate a diagnostic plan. EVIDENCE BASE:
      Appropriately designed studies to determine the utility of diagnostic techniques
      in cases with confirmed aetiology are limited. The evidence supporting this
      review is grade II, III and IV, comprising a small number of prospective studies,
      several case series, reviews, extrapolation from other species,
      pathophysiological justification and combined clinical experience of those
      working in the field.

PMID- 20800211
TI  - Alternative sampling site for blood glucose testing in cats: giving the ears a
      rest.
AB  - BACKGROUND AND STUDY RATIONALE: Home monitoring is an important part of the long
      term management of diabetic cats. Despite the extensive use of glucometers in
      this species, up until now only the pinna of the ear has been validated as a
      testing site. This cross-sectional study investigated the feasibility and
      validity of sampling from the metacarpal/metatarsal pads in hospitalised cats
      with various diseases. INVESTIGATIONS: The large pads were compared with the ear
      as a sampling site in 75 cats. Lancing the pads was tolerated very well. If the
      initial drop of blood was too small, an adequate volume of blood was almost
      always achieved by squeezing the pads. No significant differences were observed
      in first-attempt success rate or glucose values between the two sites. Due to the
      inability to obtain an adequate volume of blood or struggling, no measurement was
      possible in four cats. PRACTICAL RELEVANCE: While further work is necessary to
      assess the utility of this technique, especially in the home environment, the
      results indicate that the metacarpal pads, in particular, may offer a viable
      alternative testing site for the measurement of blood glucose concentrations,
      especially if ear sampling fails.

PMID- 20800212
TI  - Invasive mould infections of the naso-orbital region of cats: a case involving
      Aspergillus fumigatus and an aetiological review.
AB  - CASE AND CONTEXT: This report describes a cat diagnosed with sinonasal-orbital
      Aspergillus fumigatus infection using advanced imaging, histopathology and
      culture. Aetiology, clinical aspects and treatment of this rare and devastating
      infection are discussed with reference to a literature review of invasive mould
      (ie, filamentous fungal) infections involving tissues of the naso-orbital region
      of cats. PRESENTATIONS: Invasive fungal infections can present with different
      localisations (nasal passages, sinuses, orbits, subcutaneous space, palate, etc)
      depending on the species involved and its means of introduction into the tissues.
      Localised subcutaneous lesions (swellings, ulcerations, masses, nodules, etc),
      without concomitant signs of nasal/orbital disease, generally result from
      traumatic injuries and subsequent inoculation of fungal spores into the
      subcutaneous space. In contrast, naso-ocular involvement and concurrent signs of
      nasal disease (nasal discharge, sneezing, masses protruding from the nostrils)
      generally result from inhalation of spores, with subsequent spread of infection
      into the nasal planum or penetration of overlying bone and invasion of the
      subcutaneous space. Aspergillus species typically show such an invasion mechanism
      and frequently affect orbital tissues. Dematiaceous fungi (ie, filamentous fungi
      with brown/black hyphae) are reported to cause solitary, less invasive, slowly
      developing lesions, probably as a result of traumatic injuries with inoculation
      of fungal propagules. Accordingly, the subcutaneous space is more frequently
      primarily involved. TREATMENT AND OUTCOME: Whatever the mould species, reported
      treatment options include surgery and a series of antifungal drugs. The outcome
      is frequently poor, especially for Aspergillus infections, although various
      measures can be taken to maximise the chances of success, as discussed in this
      report.

PMID- 20800213
TI  - Reproduction control - new developments, old debates.

PMID- 20800214
TI  - Risk of deep venous thrombosis and pulmonary embolism in urogynecologic surgical
      patients.
AB  - OBJECTIVE: We sought to determine the incidence of symptomatic deep venous
      thrombosis and pulmonary embolism, collectively referred to as venous
      thromboembolic events (VTE), in patients undergoing urogynecologic surgery to
      guide development of a VTE prophylaxis policy for this patient population. STUDY
      DESIGN: We conducted a retrospective analysis of VTE incidence among women
      undergoing urogynecologic surgery over a 3-year period. All patients wore
      sequential compression devices intraoperatively through hospital discharge.
      RESULTS: Forty of 1104 patients (3.6%) undergoing urogynecologic surgery were
      evaluated with chest computed tomography, lower extremity ultrasound, or both for
      suspicion of VTE postoperatively. The overall rate of venous thromboembolism in
      this population was 0.3% (95% confidence interval, 0.1-0.8). CONCLUSION: Most
      women undergoing incontinence and reconstructive pelvic surgery are at a low risk
      for VTE. Sequential compression devices appear to provide adequate VTE
      prophylaxis in this patient population.

PMID- 20800215
TI  - The impact of maternal age on fetal death: does length of gestation matter?
AB  - OBJECTIVE: The objective of the investigation was to study the association of
      fetal death with maternal age by length of gestation. STUDY DESIGN: This was a
      population study including all ongoing pregnancies after 16 weeks of gestation in
      Norway during the period 1967-2006 (n = 2,182,756). RESULTS: The risk of fetal
      death was 1.4 times higher in women 40-44 years old than in women aged 20-24
      years in midpregnancy but 2.8 times higher at term. In term pregnancies the
      relative importance of maternal age increased by additional pregnancy weeks. In
      gestational weeks 42-43, the crude risk was 5.1 times higher in mothers 40 years
      old or older. In the recent period, the elevated risk of fetal death in elderly
      mothers at term has been attenuated. CONCLUSION: Women 40 years old or older had
      the highest risk of fetal death throughout pregnancy, particularly in term and
      postterm pregnancies. Improved obstetric care may explain the attenuation of risk
      associated with age in recent time.

PMID- 20800216
TI  - Detection of cervical cancer and its precursors by endocervical curettage in
      13,115 colposcopically guided biopsy examinations.
AB  - OBJECTIVE: Endocervical curettage (ECC) specimens obtained during colposcopy can
      detect cervical cancer and precursors otherwise missed by biopsy alone, but the
      procedure can be painful and reduce compliance with needed follow-up. ECC is
      routinely performed in the Calgary Health Region colposcopy clinics, permitting a
      look at its real-world utility. STUDY DESIGN: We analyzed pathology and
      colposcopy reports from 2003 to 2007. We calculated the added diagnostic utility
      of ECC compared with cervical biopsy alone. RESULTS: ECC increased the diagnostic
      yield of cervical intraepithelial neoplasia grade 2 or worse (cervical
      intraepithelial neoplasia [CIN]2+) in 1.01% of 13,115 colposcopically guided
      biopsy examinations. Therefore, 99 ECC specimens were taken to detect 1
      additional CIN2+. ECC detected 5.4% of 2443 CIN2+ subjects otherwise missed by
      biopsy alone. Utility was greatest among women aged 46 years or older referred
      after a high-grade cytology. CONCLUSION: ECC is rarely informative when used
      routinely in colposcopic practice. Older women referred after high-risk cytology
      benefit most from ECC.

PMID- 20800217
TI  - [Myocardial infarction after voluntary intoxication by drug interaction between
      dipyridamole and aspirin].
AB  - A 60-year-old male presented a myocardial infarction after a voluntary overdose
      of Asasantine((r)) started after strokes. He took chronically this association
      and some psychotropic drugs with vasodilator effects. After an intake of 40
      tablets, he presented a cardiogenic shock with a myocardial infarction confirmed
      by biological samples, EKG, echocardiography and angiocoronarographie. No recent
      change of his treatment was found and symptoms regressed when dipyridamole was
      stopped while other vasodilators drugs were continued. Chronological analysis of
      events led us to suspect dipyridamole as a starter of the myocardial infarction
      secondary to a coronary artery steal reinforced by the vasodilator effect of
      combined treatments, in a patient at risk of ischemia. This case shows that, in
      such particular conditions, a change in dipyridamole dosage can induce a
      myocardial infarction even if its blood level remains in the therapeutic range.

PMID- 20800218
TI  - [Knowledge of hypertension among hypertensive patients in general practice, and
      its relation to achieving therapeutic goals: The Co-HACT study, French West
      Indies].
AB  - OBJECTIVES: Appraisal of the agreement between patients' reports and general
      practitionners' declaration in a French Caribbean population and relationship
      with blood pressure normalization. METHODS: One hundred French Caribbean
      practitioners participated in this observational survey: each of them included
      five essential hypertensives treated for more than three months. BP was
      considered to be normalized if inferior to 140/90 mmHg. We considered that there
      is a total agreement between patient and GP declaration when SBP and DBP did not
      differ by more than 5 mmHg and when the eight risk factors or co-morbidity were
      identical. Identification of independent factors of BP normalization and
      awareness was performed using logistic regression. RESULTS: Five hundred and nine
      hypertensives (57% women) were recruited. Sixty-nine percent (n = 328) were less
      than 65 years, 75% (n = 341) had an educational level less than high school. The
      normalisation rate was 39% (n = 185) within the whole population. 63.4% had a
      high cardiovascular risk. BP normalization appeared to be closely associated to
      BP awareness. CONCLUSIONS: In this observational survey, in a French Caribbean
      hypertensive population, two third had a high cardiovascular risk. The
      normalization rate was 39%. This BP normalization appeared to be closely
      associated to BP awareness.

PMID- 20800219
TI  - [Pseudoaneurysm of the ascending aorta. Rare complication following aortic valve
      replacement].
AB  - False aneurysm of the ascending aorta has been reported as a rare complication of
      cardiovascular surgery among which the etiology, the physiopathology and the
      natural evolution are still badly known. The diagnosis is often fortuitous. The
      clinical polymorphism of the affection imposes the appeal to the morphological
      explorations to establish an early diagnosis and determine the adequate
      therapeutic attitude. This complication of the cardiac surgery is associated with
      a high mortality in spite of the cardiovascular surgery progress. In this report,
      we present a case of a pseudoaneurysm of the ascending aorta which was discovered
      six months after aortic valve replacement for severe aortic stenosis. We discuss
      in this article the diagnostic and therapeutic aspects of this case.

PMID- 20800220
TI  - Quantitative scintigraphic analysis of pulp revascularization in autotransplanted
      teeth in dogs.
AB  - OBJECTIVE: The purpose of this study was to evaluate the pulpal changes
      associated with autogenous single-rooted immature tooth transplantation in dogs,
      using either one, or two-stage surgical techniques. METHODS: Teeth from 3 beagle
      dogs, 5 months old, were extracted and transplanted to mechanically prepared
      recipient sockets. Group (A), where the teeth were transplanted using a one-stage
      method to recipient beds prepared immediately before transplantation. Group (B),
      where the teeth were transplanted using a two-stage method in which the recipient
      beds were prepared and left to heal for 7 days before transplantation. Clinical
      examinations were done every week during 9 weeks. After 9 weeks, the animals were
      injected with 99(m)Technetium hydroxylmethylene diphosphonate (99(m)Tc-HMDP) and
      3h after injection, a whole body scintigraphic acquisition was performed. After
      scintigraphic acquisition the animals were euthanized and the teeth extracted and
      its radioactivity counted in a well counter calibrated to 99(m)Tc. With the data
      obtained, the percentage of activity injected was calculated for each tooth. The
      data for each group of teeth were evaluated and analyzed using the Mann-Whitney
      test (p=0.05). RESULTS: All the transplanted teeth in both groups survived. No
      statistically significant difference was found in the absorption of the 99(m)Tc
      HMDP, between the treatment groups (p=0.464) and between them and the control
      group (Group A vs. control p=0.713 and Group B vs. control p=0.157). CONCLUSIONS:
      This study demonstrated that there was no difference between the two surgical
      techniques in terms of the pulp revascularization in transplanted teeth.

PMID- 20800221
TI  - Genome-wide association scan of trait depression.
AB  - BACKGROUND: Independent of temporal circumstances, some individuals have greater
      susceptibility to depressive affects, such as feelings of guilt, sadness,
      hopelessness, and loneliness. Identifying the genetic variants that contribute to
      these individual differences can point to biological pathways etiologically
      involved in psychiatric disorders. METHODS: Genome-wide association scans for the
      depression scale of the Revised NEO Personality Inventory in community-based
      samples from a genetically homogeneous area of Sardinia, Italy (n = 3972) and
      from the Baltimore Longitudinal Study of Aging in the United States (n = 839).
      RESULTS: Meta-analytic results for genotyped or imputed single nucleotide
      polymorphisms indicate that the strongest association signals for trait
      depression were found in RORA (rs12912233; p = 6 * 10-7), a gene involved in
      circadian rhythm. A plausible biological association was also found with single
      nucleotide polymorphisms within GRM8 (rs17864092; p = 5 * 10-6), a metabotropic
      receptor for glutamate, a major excitatory neurotransmitter in the central
      nervous system. CONCLUSIONS: These findings suggest shared genetic basis
      underlying the continuum from personality traits to psychopathology.

PMID- 20800222
TI  - Antimicrobial activity of highly stable silver nanoparticles embedded in agar
      agar matrix as a thin film.
AB  - Highly stable silver nanoparticles (Ag NPs) in agar-agar (Ag/agar) as inorganic
      organic hybrid were obtained as free-standing film by in situ reduction of silver
      nitrate by ethanol. The antimicrobial activity of Ag/agar film on Escherichia
      coli (E. coli), Staphylococcus aureus (S. aureus), and Candida albicans (C.
      albicans) was evaluated in a nutrient broth and also in saline solution. In
      particular, films were repeatedly tested for antimicrobial activity after
      recycling. UV-vis absorption and TEM studies were carried out on films at
      different stages and morphological studies on microbes were carried out by SEM.
      Results showed spherical Ag NPs of size 15-25 nm, having sharp surface plasmon
      resonance (SPR) band. The antimicrobial activity of Ag/agar film was found to be
      in the order, C. albicans>E. coli>S. aureus, and antimicrobial activity against
      C. albicans was almost maintained even after the third cycle. Whereas, in case of
      E. coli and S. aureus there was a sharp decline in antimicrobial activity after
      the second cycle. Agglomeration of Ag NPs in Ag/agar film on exposure to microbes
      was observed by TEM studies. Cytotoxic experiments carried out on HeLa cells
      showed a threshold Ag NPs concentration of 60 MUg/mL, much higher than the
      minimum inhibition concentration of Ag NPs (25.8 MUg/mL) for E. coli. The
      mechanical strength of the film determined by nanoindentation technique showed
      almost retention of the strength even after repeated cycle.

PMID- 20800223
TI  - Glucans from the alkaline extract of an edible mushroom, Pleurotus florida, cv
      Assam Florida: isolation, purification, and characterization.
AB  - Three different glucans (PS-I, PS-II, and PS-III) were isolated from the alkaline
      extract of the fruiting bodies of an edible mushroom Pleurotus florida, cultivar
      Assam Florida. On the basis of total acid hydrolysis, methylation analysis,
      periodate oxidation, Smith degradation, and NMR experiments ((1)H, (13)C, DEPT
      135, DQF-COSY, TOCSY, NOESY, ROESY, HMQC, and HMBC), the structure of the
      repeating unit of these polysaccharides was established as follows: [Formula: see
      text].

PMID- 20800224
TI  - Structural characterization of glycoprotein NGAL, an early predictive biomarker
      for acute kidney injury.
AB  - Neutrophil gelatinase-associated lipocalin (NGAL) is a promising new renal
      biomarker that can reduce the time to diagnose acute kidney injury (AKI). There
      is little information available about complex glycans on NGAL. Detailed
      structural characterization of NGAL is necessary to understand the structural
      variability of NGAL used as a standard in the NGAL immunoassay. This study
      demonstrated that 7-9% of mutant (C87S) recombinant NGAL was N-glycosylated and
      no O-glycosylation was detected. The NGAL sequence was confirmed by nanoLC/MS/MS
      following in gel and in solution trypsin digestion, and the N-glycosylation site
      was localized by MS/MS. Six different mutant recombinant NGAL samples (samples A
      F) were analyzed in this study; however, these samples demonstrated two different
      glycan patterns. Forty-one N-glycans were detected in sample A and the more
      abundant N-glycans were unsialylated. Forty-three N-glycans were detected in
      sample F and the more abundant N-glycans were sialylated. Each of the other four
      samples (B-E) had a similar N-glycan pattern as sample F.

PMID- 20800225
TI  - Extraction and physico-chemical characterization of a versatile biodegradable
      polysaccharide obtained from green algae.
AB  - During the last years, considerable attention has been given to different marine
      organisms, like algae, as potential sources of valuable materials. The continuous
      demand for novel materials and technologies is high and research on the
      underexploited marine green algae, including its polysaccharidic part-ulvan, has
      increased accordingly. In this research work, a novel method for extraction of
      ulvan from green algae is proposed and demonstrated successfully. Different
      characterization techniques were employed to characterize the isolated algal
      polysaccharide, namely, on what concerns its thermal trace and crystallinity.
      Upon heating, ulvan behaves as a non-meltable polysaccharide that is thermally
      stable before degradation at 220 degrees C. Ulvan is semi-crystalline in nature
      and possesses high hygroscopic features, as revealed in this research work. Due
      to its properties, ulvan can be considered, pure or modified, as a versatile
      biodegradable polymer for different applications, including tissue engineering
      and regenerative medicine.

PMID- 20800226
TI  - Synthesis of a novel class of glycocluster with a cyclic alpha-(1->6)
      octaglucoside as a scaffold and their binding abilities to concanavalin A.
AB  - The synthesis of small glycoclusters with high affinity toward lectins is one of
      the important subjects in glycotechnology. Although cyclic alpha-(1->6)-d
      octaglucoside (CI8) is an attractive scaffold on which to put glycosyl pendants,
      the compound has only secondary hydroxyl groups, which are relatively unreactive
      for substitution reactions. The oxidation of the vicinal diols of CI8 and
      reductive amination of the resultant dialdehydes with 2-aminoethyl mannoside gave
      mannose-CI8 conjugates with a variety of average mannose incorporation numbers (2
      7). The average numbers were deduced from MALDI-TOF mass and (1)H NMR
      spectroscopy. The binding ability of mannose-CI8 conjugates to concanavalin A
      increased with the increasing numbers of average mannose incorporation, reaching
      a plateau at tetravalence, as estimated from a latex bead-based agglutination
      lectin assay. Toxicity tests demonstrated the biocompatibility of mannose-CI8
      conjugates.

PMID- 20800227
TI  - Cyclooxygenase-2 network as predictive molecular marker for clinical pregnancy in
      in vitro fertilization.
AB  - The gene expression of human endometrium on the day of oocyte retrieval of
      pregnant and nonpregnant patients in a stimulated IVF cycle was compared in two
      independent groups with different GnRH-antagonist ovarian stimulation protocols.
      The present data suggest that increased gene expression of cyclooxygenase-2,
      together with the expression of other molecules in the cyclooxygenase-2 network,
      on the day of oocyte retrieval in GnRH-antagonist cycles coincides with a lower
      probability of achieving a clinical pregnancy in this cycle.

PMID- 20800228
TI  - Troponin determination and cardiac injury.

PMID- 20800229
TI  - alpha-Smooth muscle actin and TGF-beta receptor I expression in the healing
      rabbit medial collateral and anterior cruciate ligaments.
AB  - The aim of our study was to advance the knowledge about the biological
      differences in the healing of the anterior cruciate ligament (ACL) versus the
      medial collateral ligament (MCL). We quantified alpha-smooth muscle actin (alpha
      SMA) expression and TGF-beta receptor I (TGF-betaRI) expression in experimentally
      injured rabbit ligaments (from day 3 to 12 weeks post-injury). Myofibroblasts
      (alpha-SMA positive cells) were identified as early as the third day post-injury
      in MCL and their density increased steadily up to day 21. Myofibroblasts were
      also detected in injured ACL but their density remained very low at all time
      points. The percentage of positive TGF-betaRI area significantly increased in
      both injured ligaments compared to controls, with a peak expression at day 21;
      however, it remained constantly lower in ACL compared to MCL. A significant
      correlation was found between the percentage of TGF-betaRI positive cells and the
      percentage of alpha-SMA expression only in injured MCL. These results provide
      evidence that myofibroblasts are important players in MCL remodelling after
      injury. The combined presence of myofibroblasts and TGF-betaRI in the first 3
      weeks post-MCL injury may partially explain the difference in the MCL and ACL
      healing process.

PMID- 20800230
TI  - Feedback control from the jaw joints during biting: an investigation of the
      reptile Sphenodon using multibody modelling.
AB  - Sphenodon, a lizard-like reptile, is the only living representative of a group
      that was once widespread at the time of the dinosaurs. Unique jaw mechanics
      incorporate crushing and shearing motions to breakdown food, but during this
      process excessive loading could cause damage to the jaw joints and teeth. In
      mammals like ourselves, feedback from mechanoreceptors within the periodontal
      ligament surrounding the teeth is thought to modulate muscle activity and thereby
      minimise such damage. However, Sphenodon and many other tetrapods lack the
      periodontal ligament and must rely on alternative control mechanisms during
      biting. Here we assess whether mechanoreceptors in the jaw joints could provide
      feedback to control muscle activity levels during biting. We investigate the
      relationship between joint, bite, and muscle forces using a multibody computer
      model of the skull and neck of Sphenodon. When feedback from the jaw joints is
      included in the model, predictions agree well with experimental studies, where
      the activity of the balancing side muscles reduces to maintain equal and minimal
      joint forces. When necessary, higher, but asymmetric, joint forces associated
      with higher bite forces were achievable, but these are likely to occur
      infrequently during normal food processing. Under maximum bite forces associated
      with symmetric maximal muscle activation, peak balancing side joint forces were
      more than double those of the working side. These findings are consistent with
      the hypothesis that feedback similar to that used in the simulation is present in
      Sphenodon.

PMID- 20800231
TI  - Electrochromatography in cyclic olefin copolymer microchips: a step towards field
      portable analysis.
AB  - In order to develop a portable and disposable instrument for on-site analysis of
      neutral compounds, a lauryl methacrylate monolith has been synthesized into a
      cyclic olefin copolymer microdevice for reversed-phase electrochromatography
      purposes. This monolith was tested in capillary to evaluate
      electrochromatographic performances in terms of electroosmotic flow (EOF)
      mobility, retention and efficiency prior to its transfer into the microfluidic
      device. The produced monolithic bed exhibited a good run-to-run repeatability,
      column-to-column reproducibility and batch-to-batch reproducibility, with
      relative standard deviation (RSD) values below 9% for EOF mobility, retention
      factors and heights of theoretical plate. The electrochromatographic performances
      of the monolith were optimized by reducing irradiation time. Photopolymerization
      time of 10 min was found to be the best process in order to obtain a robust,
      retentive and efficient system. The on-chip performances of this monolith were
      evaluated in detail for the reversed-phase electrochromatographic separation of
      polycyclic aromatic hydrocarbons, with plate heights reaching down to 15 MUm when
      working at optimal velocity. Aiming at the maximum simplification of instrumental
      fabrication and operation, a direct injection from a 2 MUL droplet was compared
      with more conventional dynamic injection process.

PMID- 20800232
TI  - Automated alignment of one-dimensional chromatographic fingerprints.
AB  - A general framework for the automatic alignment of one-dimensional
      chromatographic signals is presented in this article. The alignment of signals
      was achieved by explicitly modeling the warping function. Its shape was estimated
      using a linear combination of several B-spline functions. The coefficients of the
      spline functions were found in the course of an optimization procedure to
      maximize the Pearson's correlation coefficient between a target chromatogram and
      aligned chromatogram(s). The computational requirements of the method are
      discussed with respect to the correlation optimized warping method, frequently
      used for the alignment of chromatographic signals. As illustrated with two sets
      of one-dimensional chromatographic fingerprints, the automatic alignment approach
      performs well even when non-linear peak shifts need to be corrected. It can be
      applied in an on-the-fly manner since the alignment of signals is rapid.

PMID- 20800234
TI  - Determination of melamine and cyanuric acid in powdered milk using injection-port
      derivatization and gas chromatography-tandem mass spectrometry with furan
      chemical ionization.
AB  - A reliable, sensitive and eco-friendly injection-port trimethylsilylated (TMS)
      derivatization and gas chromatography-tandem mass spectrometry (GC-MS/MS) with
      furan chemical ionization (furan-CI) method was developed to determine melamine
      and cyanuric acid in powdered milk samples. The effects of several parameters
      related to the TMS-derivatization process (i.e., injection-port temperature,
      residence time and volume of silylating agent) and of various CI agents were
      investigated. Addition of a solution (3 MUL) of
      bis(trimethyl)silyltrifluoroacetamide (BSTFA) containing 1% trimethylchlorosilane
      (TMCS) reagent to a 20-MUL extract from the powdered milk sample gave an
      excellent yield of the tris-TMS-derivatives of melamine and cyanuric acid at an
      injection-port temperature of 90 degrees C. Furthermore, using furan as the CI
      agent in conjunction with tandem mass spectrometry provided the greatest
      sensitivity and selectivity of detection. The limits of quantitation (LOQs) for
      melamine and cyanuric acid were 0.5 and 1.0 ng/g in 0.5-g of powdered milk
      samples, respectively. The recoveries from spiked samples--after simple ultra
      sonication with 5% dimethyl sulfoxide in acetonitrile coupled with n-hexane
      liquid-liquid extraction--ranged from 72% to 93% with relative standard
      deviations of lower than or equal to 18%. In three of four real powdered milk
      samples, melamine was detected at concentrations ranging from 36 to 1460 ng/g;
      and cyanuric acid was detected in two of these samples at concentrations of 17
      and 180 ng/g.

PMID- 20800233
TI  - Peptide affinity chromatography media that bind N(pro) fusion proteins under
      chaotropic conditions.
AB  - To design a generic purification platform and to combine the advantages of fusion
      protein technology and matrix-assisted refolding, a peptide affinity medium was
      developed that binds inclusion body-derived N(pro) fusion proteins under
      chaotropic conditions. Proteins were expressed in Escherichia coli using an
      expression system comprising the autoprotease N(pro) from Pestivirus, or its
      engineered mutant called EDDIE, with C-terminally linked target proteins. Upon
      refolding, the autoprotease became active and cleaved off its fusion partner,
      forming an authentic N-terminus. Peptide ligands binding to the autoprotease at 4
      M urea were screened from a combinatorial peptide library. A group of positive
      peptides were identified and further refined by mutational analysis. The best
      binders represent a common motif comprising positively charged and aromatic amino
      acids, which can be distributed in a random disposition. Mutational analysis
      showed that exchange of a single amino acid within the peptide ligand caused a
      total loss of binding activity. Functional affinity media comprising hexa- or
      octapeptides were synthesized using a 15-atom spacer with terminal sulfhydryl
      function and site-directed immobilization of peptides derivatized with iodoacetic
      anhydride. The peptide size was further reduced to dipeptides comprising only one
      positively charged and one aromatic amino acid. Based on this, affinity media
      were prepared by immobilization of a poly amino acid comprising lysine or
      arginine, and tryptophan, phenylalanine, or tyrosine, respectively, in certain
      ratios. Binding capacities were in the range of 7-15 mg protein mL(-1) of medium,
      as could be shown for several EDDIE fusion proteins. An efficient protocol for
      autoproteolytic cleavage using an on-column refolding method was implemented.

PMID- 20800235
TI  - Tuning the selectivity of polymeric ionic liquid sorbent coatings for the
      extraction of polycyclic aromatic hydrocarbons using solid-phase microextraction.
AB  - A new generation polymeric ionic liquid (PIL), poly(1-4-vinylbenzyl)-3
      hexadecylimidazolium bis[(trifluoromethyl)sulfonyl]imide (poly(VBHDIm(+) NTf(2)(
      ))), was synthesized and is shown to exhibit impressive selectivity towards the
      extraction of 12 polycyclic aromatic hydrocarbons (PAHs) from aqueous samples
      when used as a sorbent coating in direct-immersion solid-phase microextraction
      (SPME) coupled to gas chromatography (GC). The PIL was imparted with aromatic
      character to enhance pi-pi interactions between the analytes and the sorbent
      coating. For comparison purposes, a PIL with similar structure but lacking the pi
      pi interaction capability, poly(1-vinyl-3-hexadecylimidazolium
      bis[(trifluoromethyl)sulfonyl]imide) (poly(HDIm(+) NTf(2)(-))), as well as a
      commercial polydimethylsiloxane (PDMS) sorbent coating were evaluated and
      exhibited much lower extraction efficiencies. Extraction parameters, including
      stir rate and extraction time, were studied and optimized. The detection limits
      of poly(VBHDIm(+) NTf(2)(-)), poly(HDIm(+) NTf(2)(-)), and PDMS coatings varied
      between 0.003-0.07 MUg L(-1), 0.02-0.6 MUg L(-1), and 0.1-6 MUg L(-1),
      respectively. The partition coefficients (logK(fs)) of eight PAHs to the three
      studied fiber coatings were estimated using a static SPME approach. This study
      represents the first report of analyte partition coefficients to any PIL-based
      material.

PMID- 20800236
TI  - Dimeric and monomeric surfactants derived from sulfur-containing amino acids.
AB  - Anionic urea-based dimeric (gemini) surfactants derived from the amino acids L
      cystine, D-cystine and DL-cystine, as well as monomeric surfactants derived from
      L-cysteine, L-methionine and L-cysteic acid were synthesized and their solution
      properties characterized by electrical conductivity, equilibrium surface tension,
      and steady-state fluorescence spectroscopy techniques. The geminis studied showed
      the lowest critical micelle concentration (cmc) values, however the monomeric
      cysteine counterpart exhibited superior efficiency in lowering surface tension,
      an unusual finding that can be attributed to the free sulfhydryl group. Chirality
      seems to play a role in the surface active properties of the gemini surfactants,
      but not on micelle formation. All the surfactants studied showed a higher
      preference for adsorption at the air/water interface rather than to form
      micelles, a fact that may be related to the urea moiety. The polarity of the
      interfacial region, measured with the solvatochromic probe E(T)(30) (Reichardt's
      betaine dye), was similar to sodium dodecyl sulphate (SDS) micelles.

PMID- 20800237
TI  - On the composition fluctuations of reverse micelles.
AB  - The polydispersity of the reverse micelles is determined mainly by the
      fluctuations of their composition. The composition of the reverse micelle is a
      two-dimensional random variable whose components are the numbers of water (i) and
      surfactant (j) molecules. In this study the fluctuations of the composition of
      the reverse micelles are considered in the Gaussian approximation. It is shown
      that the standard deviation of the quantity w=i/j may be calculated from the
      dependence of the water vapor pressure above the microemulsion on the molar ratio
      W=[water]/[surfactant]. The estimation based on the literature data for
      microemulsion system sodium bis(2-ethylhexyl)sulfosuccinate/water/isooctane at 37
      degrees C in the range W=0-18 has shown that the relative standard deviation of
      the quantity w is about 10%. It is shown that the value of the composition
      fluctuations is related to the dependence of average composition on the
      concentration of reverse micelles at constant parameter W.

PMID- 20800238
TI  - Formation of core (polystyrene)-shell (polybenzimidazole) nanoparticles using
      sulfonated polystyrene as template.
AB  - We report formation of core (polystyrene)-shell (polybenzimidazole) nanoparticles
      from a new blend system consisting of an amorphous polymer polybenzimidazole
      (PBI) and an ionomer sodium salt of sulfonated polystyrene (SPS-Na). The ionomer
      used for the blending is spherical in shape with sulfonate groups on the surface
      of the particles. An in depth investigation of the blends at various sulfonation
      degrees and compositions using Fourier transform infrared (FT-IR) spectroscopy
      provides direct evidence of specific hydrogen bonding interactions between the N
      H groups of PBI and the sulfonate groups of SPS-Na. The disruption of PBI chains
      self association owing to the interaction between the functional groups of these
      polymer pairs is the driving force for the blending. Thermodynamical studies
      carried out by using differential scanning calorimeter (DSC) establish partially
      miscible phase separated blending of these polymers in a wider composition range.
      The two distinguishable glass transition temperatures (T(g)) which are different
      from the neat components and unaltered with the blends composition attribute that
      the domain size of heterogeneity (d(d)) of the blends is >20 nm since one of the
      blend component (SPS-Na particle) diameter is ~70 nm. The diminish of PBI chains
      self association upon blending with SPS-Na particles and the presence of
      invariant T(g)'s of the blends suggest the wrapping of PBI chains over the SPS-Na
      spherical particle surface and hence resulting a core-shell morphology.
      Transmission electron microscopy (TEM) study provides direct evidence of core
      shell nanoparticle formation; where core is the polystyrene and shell is the PBI.
      The sulfonation degree affects the blends phase separations. The higher degree of
      sulfonation favors the disruption of PBI self association and thus forms
      partially miscible two phases blends with core-shell morphology.

PMID- 20800239
TI  - Porcine circovirus type 2 morphogenesis in a clone derived from the l35
      lymphoblastoid cell line.
AB  - Porcine circovirus type 2 (PCV2) is the essential infectious agent of post
      weaning multisystemic wasting syndrome (PMWS), one of the most important diseases
      of swine. Although several studies have described different biological properties
      of the virus, some aspects of its replication cycle, including ultrastructural
      alterations, remain unknown. The aim of the present study was to describe for the
      first time a complete morphogenesis study of PCV2 in a clone of the
      lymphoblastoid L35 cell line at the ultrastructural level using electron
      microscopy techniques. Cells were infected with PCV2 at a multiplicity of
      infection of 10 and examined at 0, 6, 12, 24, 48, 60 and 72h post-infection. PCV2
      was internalized by endocytosis, after which the virus aggregated in
      intracytoplasmic inclusion bodies (ICIs). Subsequently, PCV2 was closely
      associated with mitochondria, completing a first cytoplasmic phase. The virus
      entered the nucleus for replication and virus assembly and encapsidation occurred
      with the participation of the nuclear membrane. Immature virions left the nucleus
      and formed ICIs in a second cytoplasmic phase. The results suggest that at the
      end of the replication cycle (between 24 and 48h), PCV2 was released either by
      budding of mature virion clusters or by lysis of apoptotic or dead cells. In
      conclusion, the L35-derived clone represents a suitable in-vitro model for PCV2
      morphogenesis studies and characterization of the PCV2 replication cycle.

PMID- 20800240
TI  - Cerebro- and cardiovascular reactivity and neuropsychological performance in
      hypertensive patients.
AB  - BACKGROUND: Hypertensive (HT) patients are at higher risk of cognitive decline
      than normotensive individuals, because high blood pressure is a risk factor for
      mild cognitive deterioration. In this study cardio- and cerebrovascular
      reactivity along with cognitive performance was assessed on newly diagnosed HT
      patients. METHODS: Diagnosis of hypertension was based on international
      recommendations. None of the patients had diabetes, and all of them had normal
      cerebral CT scan. Eighty-one patients (43.5+/-10.2 years, male/female ratio:
      42/39) were compared with 94 healthy controls (44+/-9.4 years, male/female ratio:
      50/44). In both groups continuous, non-invasive and simultaneous monitoring of
      cerebral and cardiac hemodynamical parameters were recorded during head-up tilt
      table testing (HUTT). Reaction time, attention and memory skills, anxiety and
      depression rate were determined by neuropsychological tests. RESULTS: During HUTT
      significant differences were found in certain cardiovascular parameters (blood
      pressure, total peripheral resistance index, stroke index), but no differences
      were detected in cerebral blood flow velocity. While there was no significant
      difference in reaction time between the two groups, tests estimating short-term
      memory (Digit Span Test) differed significantly. Moreover, sum of standardized
      test scores was significantly lower, while anxiety level was significantly
      increased in HT patients compared to controls. CONCLUSION: Decrease in
      neuropsychological performance along with alterations of cardiovascular
      parameters is an early manifestation of hypertension. Aim for an early
      intervention and accurate treatment is crucial for preventing further
      impairments.

PMID- 20800241
TI  - Cardiotomy suction, but not open venous reservoirs, activates coagulofibrinolysis
      in coronary artery surgery.
AB  - OBJECTIVES: Closed and miniaturized cardiopulmonary bypass circuits, which
      eliminate cardiotomy suction and open venous reservoirs with a reduced priming
      volume, have been reported to be advantageous. We comparatively examined the
      respective contribution of cardiotomy suction and open venous reservoirs to
      perioperative activation in coagulofibrinolysis and inflammation systems, with
      identical conditions of priming volume and anticoagulation. METHODS: A total of
      75 consecutive coronary artery bypass grafting procedures were performed using 1
      of the following 3 cardiopulmonary bypass circuits under identical conditions of
      priming volumes, heparin coating, and protocols of anticoagulation and
      transfusion, as follows: a circuit with an open venous reservoir and cardiotomy
      suction (open group, n = 25), a circuit with an open venous reservoir without
      cardiotomy suction (nonsuction group, n = 25), or a circuit without either
      (closed group, n = 25). Blood samples were collected at 8 points up to the first
      postoperative morning. RESULTS: The thrombin-antithrombin III complex, fibrinogen
      degeneration products, D-dimer, plasmin-alpha2 plasmin inhibitor complex, and
      plasminogen activator inhibitor-1 levels were significantly greater in the open
      group than those in the other 2 groups (P < .0001, for all markers). The C3a and
      interleukin-6 levels were similar among all the groups. The incidences of
      perioperative transfusion and postoperative bleeding were increased and the early
      graft patency rate of saphenous veins was lower in the open group than those in
      the other 2 groups. CONCLUSIONS: Cardiotomy suction, but not open venous
      reservoirs, causes perioperative coagulofibrinolysis activation, although neither
      affects the inflammation system. The use of cardiotomy suction needs to be
      examined further in association with postoperative PAI-1 elevation and early vein
      graft occlusion.

PMID- 20800243
TI  - A combined procedure of thoracoabdominal aortic aneurysm repair and coronary
      artery bypass grafting: report of two cases.

PMID- 20800242
TI  - Optimized temporary biventricular pacing acutely improves intraoperative cardiac
      output after weaning from cardiopulmonary bypass: a substudy of a randomized
      clinical trial.
AB  - OBJECTIVE: Permanent biventricular pacing benefits patients with heart failure
      and interventricular conduction delay, but the importance of pacing with and
      without optimization in patients at risk of low cardiac output after cardiac
      surgery is unknown. We hypothesized that pacing parameters independently affect
      cardiac output. Accordingly, we analyzed aortic flow measured with an
      electromagnetic flowmeter in patients at risk of low cardiac output during an
      ongoing randomized clinical trial of biventricular pacing (n = 11) versus
      standard of care (n = 9). METHODS: A substudy was conducted in all 20 patients in
      both groups with stable pacing after coronary artery bypass grafting, valve
      surgery, or both. Ejection fraction averaged 33% +/- 15%, and QRS duration was
      116 +/- 19 ms. Effects were measured within 1 hour of the conclusion of
      cardiopulmonary bypass. Atrioventricular delay (7 settings) and interventricular
      delay (9 settings) were optimized in random sequence. RESULTS: Optimization of
      atrioventricular delay (171 +/- 8 ms) at an interventricular delay of 0 ms
      increased flow by 14% versus the worst setting (111 +/- 11 ms, P < .001) and 7%
      versus nominal atrioventricular delay (120 ms, P < .001). Interventricular delay
      optimization increased flow 10% versus the worst setting (P < .001) and 5% versus
      nominal interventricular delay (0 ms, P < .001). Optimized pacing increased
      cardiac output 13% versus atrial pacing at matched heart rate (5.5 +/- 0.5 vs 4.9
      +/- 0.6 L/min, P = .003) and 10% versus sinus rhythm (5.0 +/- 0.6 L/min, P =
      .019). CONCLUSIONS: Temporary biventricular pacing increases intraoperative
      cardiac output in patients with left ventricular dysfunction undergoing cardiac
      surgery. Atrioventricular and interventricular delay optimization maximizes this
      benefit.

PMID- 20800244
TI  - One single dose of histidine-tryptophan-ketoglutarate solution gives equally good
      myocardial protection in elective mitral valve surgery as repetitive cold blood
      cardioplegia: a prospective randomized study.
AB  - OBJECTIVES: Histidine-tryptophan-ketoglutarate (HTK-Custodiol) cardioplegic
      solution is administered as one single dose for more than 2 hours of ischemia. No
      prospective randomized clinical study has compared the effects of HTK and cold
      blood cardioplegia on myocardial damage in elective mitral valve surgery. Thus,
      the main aim of the present study was to examine whether one single dose of cold
      antegrade HTK gives as good myocardial protection as repetitive antegrade cold
      blood cardioplegia in mitral valve surgery. METHODS: Eighty consecutive patients
      undergoing elective isolated mitral valve surgery for mitral regurgitation, with
      or without ablation for atrial fibrillation, were included in the study and
      randomized to HTK or blood cardioplegia. Markers of myocardial injury (troponin-T
      and creatine kinase MB) were analyzed at baseline and 7 hours, 1 day, 2 days, and
      3 days after surgery. RESULTS: No significant difference in creatine kinase MB
      and troponin-T between HTK and blood cardioplegia groups was found at any time
      point. There was a significant correlation between ischemic time and markers of
      myocardial injury in the HTK group only and significantly more spontaneous
      ventricular fibrillation after release of crossclamping in the HTK group.
      CONCLUSIONS: One single dose of antegrade cold HTK cardioplegic solution in
      elective mitral valve surgery protects the myocardium equally well as repetitive
      antegrade cold blood cardioplegia.

PMID- 20800245
TI  - Chronic thromboembolic pulmonary hypertension in pediatric patients.
AB  - OBJECTIVE: Chronic thromboembolic pulmonary hypertension is a rare form of
      pulmonary hypertension that can lead to progressive right heart failure and
      death. Pulmonary thromboendarterectomy surgery is the treatment of choice
      resulting in significant improvements in functional status, cardiopulmonary
      hemodynamics, and survival. This study reports the largest case series of
      pediatric patients with chronic thromboembolic pulmonary hypertension who
      underwent pulmonary thromboendarterectomy surgery at one institution. PATIENT AND
      METHODS: The University of California, San Diego, chronic thromboembolic
      pulmonary hypertension database identified patients 18 years or younger at the
      time of pulmonary thromboendarterectomy surgery (n = 17). Medical charts were
      reviewed for hemodynamics, thromboembolic risk factors, and postoperative
      outcomes. RESULTS: Pulmonary thromboendarterectomy surgery in pediatric patients
      resulted in improved functional status and significantly improved cardiopulmonary
      hemodynamics: mean arterial pressure decreased from 45.5 mm Hg +/- 20.7 to 27.3
      +/- 13.0 mm Hg (P = .00073), pulmonary vascular resistance decreased from 929 +/-
      dynes . s . cm(-5) to 299 +/- 307 dynes . s . cm(-5) (P = .0012), and cardiac
      output improved from 3.8 +/- 1.1 L/min to 5.6 +/- 1.6 L/min (P = .0061). There
      were no deaths during surgery or 30 days after surgery, and long-term survival
      (5+ years) was achieved in 87.5%. As compared to adults with chronic
      thromboembolic pulmonary hypertension, there was a higher rate of rethrombosis in
      pediatric patients (38% vs 1%-4%). CONCLUSIONS: This study demonstrates that
      pulmonary thromboendarterectomy surgery in pediatric patients with chronic
      thromboembolic pulmonary hypertension is well tolerated with improved
      postoperative hemodynamics, functional status, minimal postoperative
      complications, and low perioperative mortality, similar to that reported for
      adults with chronic thromboembolic pulmonary hypertension, with the notable
      exception being a higher rate of rethrombosis in pediatric patients.

PMID- 20800246
TI  - Immunohistochemical evaluation of surfactant proteins and lymphocyte phenotypes
      in the lungs of cattle with natural tuberculosis.
AB  - The aim of the present study was to evaluate the immunohistochemical expression
      of pulmonary surfactant proteins (SP-A, SP-B, SP-C) and lymphocytic phenotypes in
      the lungs of 12 cattle with natural tuberculosis. Grossly, the disease-affected
      cattle revealed numerous granulomas in the lung lobes. Histopathological
      examination found multiple lung granulomas with typical cellular elements. Type
      II pneumocytes with adenomatous proliferation around the granulomas were strongly
      immunopositive for SP-A and SP-B compared to normal type II cells. Clara cells
      showed also cytoplasmic immunopositivity for these surfactant proteins. Positive
      immunolabelling for proSP-C was detected exclusively in the normal and
      proliferative type II pneumocytes, and the reaction was marked in the perinuclear
      area of the cells. CD3(+) T and CD79alphacy(+) B lymphocytes were predominantly
      localized in the fibrotic capsule margin of advanced granulomas, in greater
      numbers than in the early granulomas. In conclusion, the study found that type II
      pneumocytes proliferated highly and surrounded the tuberculous granulomas in the
      lungs, that hyperplastic type II pneumocytes synthesized and secreted larger
      amounts of surfactant proteins than the normal type II cells, and that SP-A might
      have played an important role in host defence against the mycobacterial agents.
      Additionally, the presence of high numbers of CD3(+) T cells throughout the
      granulomas confirmed the dominance of a cellular immune response in cattle
      tuberculosis.

PMID- 20800247
TI  - Naringin and vitamin E influence the oxidative stability and lipid profile of
      plasma in lambs fed fish oil.
AB  - Thirty two Merino lambs (15 weeks old) fed barley straw and fish oil enriched
      concentrate were used to assess the effect of vitamin E (6 g kg(-1) DM) and
      naringin (1.5-3 g kg(-1) DM) on plasma lipid peroxidation (TBARS), total
      antioxidant status (TAS), immune response, plasma cholesterol, and triglycerides.
      After 21 days feeding the experimental diets, lambs were subjected to a 4 h
      transportation stress period and then held 4 more hours without feed. TBARS
      values before stress were lower for animals consuming vitamine E and naringin
      when compared to control lambs (P<0.05). However, after stress all groups
      presented similar levels of TBARS. TAS decreased (P<0.05) in all groups in
      response to stress with values recovering (P<0.05) to pre-stress values following
      4 h of rest. A rise (P<0.05) in serum concentrations of triacylglycerol following
      21 d of fish oil supplementation was dampened in lambs consuming vitamin E or
      naringin. Both pre-stress TBARS and triacylglycerol-reducing effects of naringin
      added to fish oil enriched concentrate for fattening lambs are reported.

PMID- 20800248
TI  - Pharmacokinetics and bioavailability of a long-acting formulation of cephalexin
      after intramuscular administration to cats.
AB  - The pharmacokinetic profile and bioavailability of a long-acting formulation of
      cephalexin after intramuscular administration to cats was investigated. Single
      intravenous (cephalexin lysine salt) and intramuscular (20% cephalexin
      monohydrate suspension) were administered to five cats at a dose rate of 10
      mg/kg. Serum disposition curves were analyzed by noncompartmental approaches.
      After intravenous administration, volume of distribution (V(z)), total body
      clearance (Cl(t)), elimination constant (lambda(z)), elimination half-life
      (t(1/2)(lambda)) and mean residence time (MRT) were: 0.33+/-0.03 L/kg; 0.14+/
      0.02 L/hkg, 0.42+/-0.05 h(-1), 1.68+/-0.20 h and 2.11+/-0.25 h, respectively.
      Peak serum concentration (C(max)), time to peak serum concentration (T(max)) and
      bioavailability after intramuscular administration were 15.67+/-1.95 MUg/mL,
      2.00+/-0.61 h and 83.33+/-8.74%, respectively.

PMID- 20800249
TI  - Ivermectin impairs sexual behavior in sexually naive, but not sexually
      experienced male rats.
AB  - Ivermectin (IVM) is an antiparasitic drug, widely used in domestic animals. In
      mammals, IVM act as a GABA agonist. This neurotransmitter has an important role
      in the regulation of sexual behavior. Thus, this study sought to investigate the
      effects of various medically relevant doses IVM on the sexual behavior of male
      rats. In particular, we also wished to examine if previous sexual experience
      modulated responses to IVM. In the first experiment, the sexual behavior of
      inexperienced male rats was analyzed after they received 0.2, 0.6, 1.0 or 2.0
      mg/kg IVM, 15 min prior to behavioral testing. In the second experiment, the
      effects of four previous sexual experiences on IVM treated rats (1.0 or 2.0
      mg/kg, 15 min prior to the 5th session) were assessed. The standard therapeutic
      dose (0.2 mg/kg) did not impair the sexual behavior of inexperienced male rats.
      At a more concentrated dose (0.6 mg/kg), which is still within the therapeutic
      range, the appetitive phase of sexual behavior of inexperienced male rats was
      impaired. Likewise, 1.0 mg/kg impaired the appetitive phase. Previous sexual
      experience blocked almost entirely this sexual impairment, suggesting that
      previous sexual experience exerts a positive effect in attenuating the sexual
      impairment produced by IVM treatment. Therefore, the standard therapeutic dose of
      IVM can be used without producing side effects on sexual behavior. Use of more
      concentrated therapeutic doses is not recommended during reproductive periods,
      unless the animals have had previous sexual experience.

PMID- 20800250
TI  - [Dysarthria across Parkinson's disease progression. Natural history of its
      components: dysphonia, dysprosody and dysarthria].
AB  - Dysarthria refers to a collective name for a group of neurologic motor speech
      disorders, resulting from central and/or peripheral nervous system abnormalities.
      Speech alteration in Parkinson's disease, so-called hypokinetic dysarthria,
      presents with prosodic insufficiency, related to a monotony of pitch and
      intensity, a reduction of accentuation, variable speech rate and possible phoneme
      imprecision. In most cases, voice is harsh and breathy. This symptom can affect
      both voice and speech quality, as well as prosody and intelligibility. As a
      consequence, many patients complain about speech impairments, which affect their
      communication in daily living activities. Perceptual and instrumental assessments
      require different and numerous investigation methods, which use may help to
      further understand the specific dysarthria pathophysiology. This is of importance
      in order to adjust treatments for dysarthria; as a matter of fact, dopa-therapy,
      functional neurosurgery or even behavioural speech therapy have variable effects
      on voice and speech quality in Parkinson's disease.

PMID- 20800251
TI  - [Severe form of hereditary neuralgic amyotrophy without SEPT9 gene mutation].
AB  - INTRODUCTION: Hereditary neuralgic amyotrophy (HNA) is a rare condition
      characterized by recurrent episodes of painful paralysis preferentially affecting
      the brachial plexus. It is often linked to a mutation in the SEPT9 gene. CASE
      REPORT: A 69-year-old female patient experienced a dozen episodes of severe
      neurological deficit mainly affecting the brachial plexus and the phrenic and
      recurrent nerves. The diagnosis of HNA without SEPT9 gene mutation was retained.
      DISCUSSION: HNA can have significant sequelae. A genetic heterogeneity exists and
      mutations in the SEPT9 gene may not be found. Immunomodulatory and corticosteroid
      treatments have sometimes proved to be effective.

PMID- 20800252
TI  - All serotypes of dengue virus induce HLA-A2 major histocompatibility complex
      class I promoter activity in human liver cells.
AB  - In contrast to many viruses that escape the host's immune responses by
      suppressing the major histocompatibility complex (MHC) class I pathway,
      flaviviruses have been shown to up-regulate the cell surface expression of MHC
      class I complex. The mechanism by which dengue virus (DV) achieves this up
      regulation remains unclear. Our investigation on the HLA-A2 gene in human liver
      cells demonstrated that all four serotypes of dengue virus, DV1 to DV4, resulted
      in variable degrees of promoter induction. This illustrates the importance of MHC
      class I transcription regulation in primary infections by different DV serotypes
      that may have even greater impact in secondary infections, associated with
      increased disease severity.

PMID- 20800253
TI  - Attrition of HIV-infected individuals not yet eligible for antiretroviral
      treatment: do we care?

PMID- 20800254
TI  - Modified gold nanoparticle vectors: a biocompatible intracellular delivery system
      for pancreatic islet cell transplantation.
AB  - BACKGROUND: Islet transplantation is an emerging therapy for type 1 diabetes
      mellitus with variable success. Molecular therapeutics is a promising approach to
      improve islet graft function and transplant outcomes. Traditional delivery
      vectors, however, have poor cell penetration and generally lead to compromised
      islet function. Modified gold nanoparticles represent a potential alternative in
      that they are taken up into cells efficiently and have unique binding properties.
      The objective of this study was to investigate whether gold nanoparticles can
      transfect islets uniformly without compromising cellular function. METHODS: Cy5
      oligonucleotide-conjugated gold nanoparticle islet transfection was evaluated
      using confocal microscopy and flow cytometry. Isolated mice and human islets were
      transfected and evaluated for mitochondrial potential changes, calcium influx,
      and insulin secretion in response to glucose challenge and in vivo graft
      function. RESULTS: Highly efficient gold nanoparticle uptake was observed.
      Transfected islets demonstrated normal mitochondrial function, calcium influx,
      and insulin release when stimulated by glucose. These islets produced a 100%
      diabetes cure rate after transplantation. Intraperitoneal glucose tolerance test
      demonstrated similar graft function as controls. CONCLUSION: We describe the
      development of a modified gold nanoparticle approach that allows for the
      efficient and nontoxic transfection of not only single cells but also more
      complex tissue architectures, such as pancreatic islets, both in vitro and in
      vivo.

PMID- 20800255
TI  - Recurrent hyperparathyroidism and forearm parathyromatosis after total
      parathyroidectomy.
AB  - BACKGROUND: In multiple endocrine neoplasia type I and renal failure, the type of
      initial parathyroidectomy for hyperparathyroidism may influence the operative
      risks and development of recurrence. We compared subtotal parathyroidectomy with
      total parathyroidectomy and immediate forearm autotransplantation (TPFA) in a
      large series with long-term follow-up. METHODS: The data of patients treated from
      1977 to 2009 by initial or reoperative TPFA or subtotal parathyroidectomy were
      examined for outcomes including the interval to sites and tissue patterns of
      recurrence. RESULTS: Permanent hypoparathyroidism was rare and uninfluenced by
      disease type. Neither initial procedure nor underlying disease affected the mean
      time to reoperation for recurrent hyperparathyroidism. In renal failure,
      reoperation was more common after TPFA than subtotal parathyroidectomy (5/19, 26%
      vs 11/193, 6%; P = .008). Twelve patients required forearm reoperation after
      TPFA, which was often complicated by parathyromatosis (7/12, 58%). Further
      reoperative forearm surgery was more likely after explant excision than after en
      bloc resection (7/11 vs 0/8; P = .01) and occurred sooner in renal failure than
      in multiple endocrine neoplasia type I (mean 4.4 vs 9 years; P = .04). Permanent
      hypoparathyroidism was rare and uninfluenced by disease type. CONCLUSION: Because
      of frequent recurrence, TPFA should be abandoned as a treatment of renal
      hyperparathyroidism. In multiple endocrine neoplasia type I, subtotal
      parathyroidectomy has similar outcomes to TPFA. Forearm autotransplantation can
      be complicated by parathyromatosis, and surgeons should be prepared for
      reoperative en bloc resection.

PMID- 20800256
TI  - Comparison of the surface wave method and the indentation method for measuring
      the elasticity of gelatin phantoms of different concentrations.
AB  - The speed of the surface Rayleigh wave, which is related to the viscoelastic
      properties of the medium, can be measured by noninvasive and noncontact methods.
      This technique has been applied in biomedical applications such as detecting skin
      diseases. Static spherical indentation, which quantifies material elasticity
      through the relationship between loading force and displacement, has been applied
      in various areas including a number of biomedical applications. This paper
      compares the results obtained from these two methods on five gelatin phantoms of
      different concentrations (5%, 7.5%, 10%, 12.5% and 15%). The concentrations are
      chosen because the elasticity of such gelatin phantoms is close to that of tissue
      types such as skin. The results show that both the surface wave method and the
      static spherical indentation method produce the same values for shear elasticity.
      For example, the shear elasticities measured by the surface wave method are 1.51,
      2.75, 5.34, 6.90 and 8.40kPa on the five phantoms, respectively. In addition, by
      studying the dispersion curve of the surface wave speed, shear viscosity can be
      extracted. The measured shear viscosities are 0.00, 0.00, 0.13, 0.39 and 1.22Pa.s
      on the five phantoms, respectively. The results also show that the shear
      elasticity of the gelatin phantoms increases linearly with their prepared
      concentrations. The linear regressions between concentration and shear elasticity
      have R(2) values larger than 0.98 for both methods.

PMID- 20800259
TI  - A Bayesian changepoint-threshold model to examine the effect of TMDL
      implementation on the flow-nitrogen concentration relationship in the Neuse River
      basin.
AB  - In-stream nutrient concentrations are well known to exhibit a strong relationship
      with river flow. The use of flow measurements to predict nutrient concentrations
      and subsequently nutrient loads is common in water quality modeling.
      Nevertheless, most adopted models assume that the relationship between flow and
      concentration is fixed across time as well as across different flow regimes. In
      this study, we developed a Bayesian changepoint-threshold model that relaxes
      these constraints and allows for the identification and quantification of any
      changes in the underlying flow-concentration relationship across time. The
      results from our study support the occurrence of a changepoint in time around the
      year 1999, which coincided with the period of implementing nitrogen control
      measures as part of the TMDL program developed for the Neuse Estuary in North
      Carolina. The occurrence of the changepoint challenges the underlying assumption
      of temporal invariance in the flow-concentrations relationship. The model results
      also point towards a transition in the river nitrogen delivery system from a
      point source dominated loading system towards a more complicated nonlinear
      system, where non-point source nutrient delivery plays a major role. Moreover, we
      use the developed model to assess the effectiveness of the nitrogen reduction
      measures in achieving a 30% drop in loading. The results indicate that while
      there is a strong evidence of a load reduction, there still remains a high level
      of uncertainty associated with the mean nitrogen load reduction. We show that the
      level of uncertainty around the estimated load reduction is not random but is
      flow related.

PMID- 20800257
TI  - The rate of hepatitis C virus infection initiation in vitro is directly related
      to particle density.
AB  - To gain a more complete understanding of hepatitis C virus (HCV) entry, we
      initially assessed the rate at which HCV initiates productive
      attachment/infection in vitro and discovered it to be slower than most viruses.
      Since HCV, including cell culture-derived HCV (HCVcc), exhibits a broad-density
      profile (1.01-1.16 g/ml), we hypothesized that the varying densities of the HCVcc
      particles present in the inoculum may be responsible for this prolonged entry
      phenotype. To test this hypothesis, we show that during infection, particles of
      high density disappeared from the viral inoculum sooner and initiated productive
      infection faster than virions of low density. Moreover, we could alter the rate
      of attachment/infection initiation by increasing or decreasing the density of the
      cell culture medium. Together, these findings demonstrate that the relationship
      between the density of HCVcc and the density of the extracellular milieu can
      significantly impact the rate at which HCVcc productively interacts with target
      cells in vitro.

PMID- 20800258
TI  - The nuclear localization of low risk HPV11 E7 protein mediated by its zinc
      binding domain is independent of nuclear import receptors.
AB  - We investigated the nuclear import of low risk HPV11 E7 protein using 1)
      transfection assays in HeLa cells with EGFP fusion plasmids containing 11E7 and
      its domains and 2) nuclear import assays in digitonin-permeabilized HeLa cells
      with GST fusion proteins containing 11E7 and its domains. The EGFP-11E7 and EGFP
      11cE7(39-98) localized mostly to the nucleus. The GST-11E7 and GST-11cE7(39-98)
      were imported into the nuclei in the presence of either Ran-GDP or RanG19V-GTP
      mutant and in the absence of nuclear import receptors. This suggests that 11E7
      enters the nucleus via a Ran-dependent pathway, independent of nuclear import
      receptors, mediated by a nuclear localization signal located in its C-terminal
      domain (cNLS). This cNLS contains the zinc binding domain consisting of two
      copies of Cys-X-X-Cys motif. Mutagenesis of Cys residues in these motifs changed
      the localization of the EGFP-11cE7/-11E7 mutants to cytoplasmic, suggesting that
      the zinc binding domain is essential for nuclear localization of 11E7.

PMID- 20800260
TI  - Contribution of Streptomyces in sediment to earthy odor in the overlying water in
      Xionghe Reservoir, China.
AB  - Musty and earthy odors frequently characterize the source water and fish of the
      Xionghe Reservoir in China. Although odorous compounds and odor-producing
      cyanobacteria have been analyzed in surface water, potential odorants in
      sediments and their contribution to the water body have remained uninvestigated.
      In this study, we examined the odorous compounds and possible odor-producers in
      the sediments and overlying water of Xionghe Reservoir from November 2007 to
      October 2008. High concentrations of geosmin (up to 5280.1 ng kg(-1) dw(-1)) were
      detected in sediments, and eight strains of Streptomyces isolated from sediments
      were verified as producers of geosmin and/or 2-MIB in M liquid medium by HSPME-GC
      MS. Geosmin concentrations in the overlying water were correlated with those in
      the sediments (r = 0.838, p < 0.05). In vitro studies showed that geosmin in the
      overlying water was released from the sediment, and that within 12 days the
      amount released from the sediment was 21.4-51.4%. Concentrations of geosmin in
      sediments were positively correlated with organic matter (r = 0.642, p < 0.01),
      total nitrogen (r = 0.606, p < 0.01) and Chl a (r = 0.674, p < 0.01), and were
      negatively associated with temperature (r = -0.425, p < 0.05). This study
      indicates that odorous compounds that are released from sediments should be taken
      into account when assessing the sources of these odorants in waters.

PMID- 20800261
TI  - Effects of water chemistry on arsenic removal from drinking water by
      electrocoagulation.
AB  - Exposure to arsenic through drinking water poses a threat to human health.
      Electrocoagulation is a water treatment technology that involves electrolytic
      oxidation of anode materials and in-situ generation of coagulant. The
      electrochemical generation of coagulant is an alternative to using chemical
      coagulants, and the process can also oxidize As(III) to As(V). Batch
      electrocoagulation experiments were performed in the laboratory using iron
      electrodes. The experiments quantified the effects of pH, initial arsenic
      concentration and oxidation state, and concentrations of dissolved phosphate,
      silica and sulfate on the rate and extent of arsenic removal. The iron generated
      during electrocoagulation precipitated as lepidocrocite (gamma-FeOOH), except
      when dissolved silica was present, and arsenic was removed by adsorption to the
      lepidocrocite. Arsenic removal was slower at higher pH. When solutions initially
      contained As(III), a portion of the As(III) was oxidized to As(V) during
      electrocoagulation. As(V) removal was faster than As(III) removal. The presence
      of 1 and 4 mg/L phosphate inhibited arsenic removal, while the presence of 5 and
      20 mg/L silica or 10 and 50 mg/L sulfate had no significant effect on arsenic
      removal. For most conditions examined in this study, over 99.9% arsenic removal
      efficiency was achieved. Electrocoagulation was also highly effective at removing
      arsenic from drinking water in field trials conducted in a village in Eastern
      India. By using operation times long enough to produce sufficient iron oxide for
      removal of both phosphate and arsenate, the performance of the systems in field
      trials was not inhibited by high phosphate concentrations.

PMID- 20800262
TI  - Characterization of endotoxic indicative organic matter (2-keto-3deoxyoctulosonic
      acid) in raw and biologically treated domestic wastewater.
AB  - The aim of this research is to characterize the organic matter showing
      endotoxicity in domestic wastewater. It is assumed that endotoxicity is caused by
      lipo-polysaccharide (LPS), particularly large and hydrophobic molecules. In this
      study, a batch experiment (decay test for 12 h) was conducted to confirm whether
      LPS is the cause of endotoxicity or not. 2-keto-3deoxyoctulosonic acid (KDO) was
      used as an indicator of presence of LPS.A size and structural characterization of
      several samples from raw and domestic wastewater was also carried out in order
      know which fractions are causing endotoxicity. Endotoxin and KDO patterns were
      found to be similar, peaking at the same time. Thus, organic matter showing
      endotoxicity, such as LPS was released in the decay test. Moreover, the organic
      matter released from bacteria during decay test was partly biodegradable. Results
      from size characterization (Molecular Weight Distribution) showed that the
      majority of endotoxin (up to 82%), in domestic sewage and secondary effluents,is
      composed of molecules larger than 100 kDa and less than 0.1 MUm. Similarly,
      structural characterization (hydrophobic and hydrophilic) showed that the
      majority of endotoxin, ranging from 59% to 83% of the total endotoxicity, is
      hydrophobic fractions. Therefore, removing large and hydrophobic molecules from
      wastewater can be an effective way to achieve a significant decrease in its
      endotoxicity.

PMID- 20800263
TI  - PCB and DDT levels do not appear to have enhanced the mortality of striped
      dolphins (Stenella coeruleoalba) in the 2007 Mediterranean epizootic.
AB  - In 2007, 17 years after the first reported Mediterranean epizootic of striped
      dolphins (Stenella coeruleoalba), a new strain of the morbillivirus caused the
      deaths of dozens of striped dolphins that appeared dead on Western Mediterranean
      beaches. DDT and PCB levels were determined in these dolphins, and in individuals
      from sporadic strandings in the surrounding years. Comparison between the two
      epidemic events showed that organochlorine (OC) levels in the dolphins from 1990
      epizootic were more than 10-fold higher for tPCB and 6-fold higher for tDDT than
      levels in dolphins from the 2007 outbreak. In contrast to what occurred in 1990,
      OCs from individuals affected by the second outburst fit well with curves of OC
      trends in the Mediterranean. Because the virulence of the 2007 epizootic was much
      lower, and the deceased dolphins affected by it did not present OC concentrations
      that were more elevated than in presumably healthy individuals, this second
      outburst is not believed to have been enhanced by OC pollutants.

PMID- 20800264
TI  - Treatment of gaseous hydrogen chloride using Mg-Al layered double hydroxide
      intercalated with carbonate ion.
AB  - It is important to treat gaseous HCl from incineration streams efficiently to
      avoid adverse environmental consequences. In this paper, a new treatment method
      for gaseous HCl is presented-the application of Mg-Al layered double hydroxide
      (LDH) intercalated with CO(3)(2-) (CO(3).Mg-Al LDH) to treat gaseous HCl
      continuously. The degree of HCl removal without water vapor is higher than that
      with water vapor; further, this reaction does not require H(2)O. In addition, the
      degree of HCl removal increases with increasing temperature, CO(3).Mg-Al LDH
      quantity, HCl concentration, and improved contact between CO(3).Mg-Al LDH and HCl
      gas. The treatment of HCl gas by CO(3).Mg-Al LDH leads to the production of Mg-Al
      LDH intercalated with Cl(-). Further, HCl is also absorbed on the surface of
      CO(3).Mg-Al LDH. Our proposed treatment method works effectively for the
      treatment of gaseous HCl from incinerator streams.

PMID- 20800265
TI  - Protein profiles in zebrafish (Danio rerio) brains exposed to chronic microcystin
      LR.
AB  - Microcystin-LR (MCLR) is a commonly encountered blue-green algal hepatotoxin and
      a known inhibitor of cellular protein phosphatase (PP), however, little is known
      about its neurotoxicity. This study investigated the protein profiles of
      zebrafish (Danio rerio) brains chronically exposed to MCLR concentrations (2 or
      20 MUg L(-1)) using the proteomic approach. The results showed that MCLR
      strikingly enhanced toxin accumulation and the PP activity in zebrafish brains
      after 30 d exposure. Comparison of two-dimensional electrophoresis protein
      profiles of MCLR exposed and non-exposed zebrafish brains revealed that the
      abundance of 30 protein spots was remarkably altered in response to MCLR
      exposure. These proteins are involved in cytoskeleton assembly, macromolecule
      metabolism, oxidative stress, signal transduction, and other functions (e.g.
      transporting, protein degradation, apoptosis and translation), indicating that
      MCLR toxicity in the fish brain is complex and diverse. The chronic neurotoxicity
      of MCLR might initiate the PP pathway via an upregulation of PP2C in the
      zebrafish brain, in addition to the reactive oxygen species pathway.
      Additionally, the increase of vitellogenin abundance in MCLR exposed zebrafish
      brains suggested that MCLR might mimic the effects of endocrine disrupting
      chemicals. This study demonstrated that MCLR causes neurotoxicity in zebrafish at
      the proteomic level, which provides a new insight into MCLR toxicity in aquatic
      organisms and human beings.

PMID- 20800266
TI  - Estimation of the carbon footprint of the Galician fishing activity (NW Spain).
AB  - The food production system as a whole is recognized as one of the major
      contributors to environmental impacts. Accordingly, food production, processing,
      transport and consumption account for a relevant portion of the greenhouse gas
      (GHG) emissions associated with any country. In this context, there is an
      increasing market demand for climate-relevant information regarding the global
      warming impact of consumer food products throughout the supply chains. This
      article deals with the assessment of the carbon footprint of seafood products as
      a key subgroup in the food sector. Galicia (NW Spain) was selected as a case
      study. The analysis is based on a representative set of species within the
      Galician fishing sector, including species obtained from coastal fishing (e.g.
      horse mackerel, Atlantic mackerel, European pilchard and blue whiting), offshore
      fishing (e.g. European hake, megrim and anglerfish), deep-sea fishing (skipjack
      and yellowfin tuna), extensive aquaculture (mussels) and intensive aquaculture
      (turbot). The carbon footprints associated with the production-related activities
      of each selected species were quantified following a business-to-business
      approach on the basis of 1year of fishing activity. These individual carbon
      footprints were used to calculate the carbon footprint for each of the different
      Galician fisheries and culture activities. Finally, the lump sum of the carbon
      footprints for coastal, offshore and deep-sea fishing and extensive and intensive
      aquaculture brought about the carbon footprint of the Galician fishing activity
      (i.e., capture and culture). A benchmark for quantifying and communicating
      emission reductions was then provided, and opportunities to reduce the GHG
      emissions associated with the Galician fishing activity could be prioritized.

PMID- 20800267
TI  - Characterisation and reproducibility of a human ex vivo model of thrombosis.
AB  - BACKGROUND: The Badimon chamber is a clinical ex vivo model of thrombosis that
      mimics flow conditions within the coronary circulation of man. The aims of this
      study were to characterise thrombus formation in the chamber and evaluate its
      reproducibility. METHODS: Using blood from 24 healthy human volunteers, thrombus
      formation was assessed at low and high shear rates with porcine aortic tunica
      media as the thrombogenic substrate. Thrombus area was measured
      histomorphometrically. Reproducibility was assessed by paired measurements made
      both within and between days. Platelet activation was assessed before and at
      selected points within the extracorporeal circuit using flow cytometry, and
      fibrin content and distribution within the thrombus were assessed by
      immunohistochemistry. RESULTS: Total thrombus area was highly reproducible within
      and between days in the low shear ([mean thrombus area, mean difference +/- SEM]
      8,018MUm(2), 58+/-204MUm(2) and 8,177MUm(2), -154+/-168MUm(2) respectively) and
      high shear chambers (11,802MUm(2), -52+/-175MUm(2) and 11,877MUm(2), 220+/
      181MUm(2) respectively). Total thrombus area was greater in the high compared to
      the low shear chamber (11,970+/-285MUm(2)versus 7,892+/-298MUm(2); P<0.0001).
      Transit through the extracorporeal circuit did not result in platelet activation
      which was only detected after blood passed across the perfusion chambers (P=0.02
      for platelet-monocyte aggregate formation and P=0.05 for P-selectin expression).
      Thrombus in the low shear chamber contained a greater proportion of fibrin
      (25.0+/-6.0% versus 8.3+/-1.6%, P<0.001). CONCLUSIONS: The Badimon chamber
      provides a highly reproducible technique for the assessment of ex vivo platelet
      rich thrombus formation in man.

PMID- 20800268
TI  - Chronic unpredictable stress accelerates atherosclerosis through promoting
      inflammation in apolipoprotein E knockout mice.
AB  - INTRODUCTION: Chronic unpredictable stress (CUS) has been suggested to accelerate
      atherosclerosis. However, the underlying mechanism of this adverse effect is not
      fully understood. Since chronic stress can promote or even initiate inflammation
      response, which is thought to be a major contributor to atherogenesis, we
      postulated that stress-induced inflammatory response might be one important
      reason for CUS-promoted atherosclerotic disease. MATERIALS AND METHODS: We used
      the CUS treated apolipoprotein E (ApoE)-deficient mice, which have been shown to
      spontaneously develop atherosclerosis with features similar to those seen in
      humans, as an animal model. Haematoxylin and eosin staining and
      immunohistostaining were used to analyze the plaque formation and composition.
      RESULTS: Histological analysis clearly demonstrated that CUS treatment promoted
      the development of atherosclerotic lesions, such as triggering plaque rupture,
      increasing plaque size and plaque-to-surface ratio, and also led to profound
      changes in plaque composition, as evidenced by increased macrophage and T cell
      infiltration and decreased smooth muscle cell mass, all reflecting an unstable
      plaque phenotype. Moreover, adhesion molecular vascular cell adhesion molecule-1
      (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), acute phase reactant C
      reactive protein (CRP), and proinflammatory cytokine interleukin-6 (IL-6) were
      significantly enhanced in CUS treated ApoE(-/-) mice compared with untreated
      control animals (P<0.01). CONCLUSION: The involvement of CUS in the pathogenesis
      of atherosclerosis is at least partially attributable to its acceleration of
      inflammation.

PMID- 20800269
TI  - Role of maximal primary cytoreductive surgery in patients with advanced
      epithelial ovarian and tubal cancer: Surgical and oncological outcomes. Single
      institution experience.
AB  - OBJECTIVE: To determinate the impact of maximal cytoreductive surgery on
      progression free survival (PFS), overall survival (OS) rates and morbidity, in
      patients with advanced epithelial ovarian or fallopian tube cancer. METHODS: We
      reviewed all medical records of patients with stages IIIC-IV epithelial ovarian
      and fallopian tube cancer that were managed at our institution between January
      2001 and December 2008. The following information was collected: demographics,
      tumor characteristics, operative information, surgical outcomes and peri
      operative complication. RESULTS: A total of 288 patients with advanced epithelial
      ovarian and fallopian tube cancer were referred to our institution between
      January 2001 and December 2008, 259 consecutive patients were enrolled in the
      study. After a median follow-up of 29.8 months, the PFS and OS were 19.9 and 57.6
      months, respectively. At univariate analysis, factors significantly associated
      with decreased PFS included: age greater than median (>60 years), stage IV,
      presence of ascites >1000 cc, presence of diffuse peritoneal carcinomatosis and
      diameter of residual disease. This was confirmed also at multivariate analysis
      with age greater than 60 years (P=0.025), stage IV vs IIIC (P=0.037) and any
      residual disease (P=0.032) having an independent association with worse PFS.
      CONCLUSIONS: Our study seems to demonstrate that a more extensive surgical
      approach is associated with prolonged disease-free interval and improved survival
      in patients with stages IIIC-IV epithelial ovarian and fallopian tube cancer.
      Moreover all patients with no residual tumor seem to have the best prognosis and
      in view of these results we believe that the goal of primary surgery should be
      considered as leaving no macroscopic disease.

PMID- 20800270
TI  - Long-term degradation of enamel and dentin bonds: 6-year results in vitro vs. in
      vivo.
AB  - OBJECTIVES: To evaluate marginal integrity of direct resin composite restorations
      before and after thermo-mechanical loading in vitro, and before and after 6 years
      of clinical service in a prospective clinical trial. METHODS: For the in vitro
      part, MO cavities with the proximal box beneath the cemento-enamel junction were
      prepared in 32 extracted human third molars. The specimens were randomly assigned
      to four groups (n=8) and received bonded resin composite restorations (two groups
      each Grandio bonded with Solobond M and Tetric Ceram bonded with Syntac).
      Specimens were subjected to three different aging protocols: 6-year water storage
      (WS), thermo-mechanical loading (TML; 100,000*50N; 2500*+5/+55 degrees C), and 6
      year water storage plus thermo-mechanical loading (WS+TML). Initially and after
      aging, marginal qualities in enamel and dentin were evaluated using replicas at
      200* magnification (SEM). For the in vivo part, 30 patients received 68 direct
      resin composite restorations of the same materials in a prospective clinical
      trial. Replicas of 11 selected subjects per group were assessed for marginal
      quality under a SEM at 200*. RESULTS: in vitro, all initial results showed nearly
      100% gap-free margins. For TML, percentages of gap-free margins dropped to 87-90%
      in enamel and to 58-66% in dentin (p<0.05). For WS, enamel margins still were at
      97-99% whereas dentin margins exhibited 67-75% gap-free margins, and for WS+TML,
      enamel margins were at 85-87% and dentin margins at 42-52% gap-free margins. In
      vivo, gap-free enamel margins were reduced from initially 86-90% to 74-80% after
      6 years of clinical service (p<0.05). Proximally exposed dentin margins were not
      recordable by impressions, however, clinically no considerable problems like
      recurrent caries or discolorations were detected. SIGNIFICANCE: In vitro,
      hydrolytic degradation supports mechanical fatigue in dentin-composite bonds over
      time. In vivo, wear phenomena are superimposing marginal quality aspects. Gaps
      between enamel and resin composite did not play a major role.

PMID- 20800271
TI  - Identification of a mutation in complement factor H-related protein 5 in patients
      of Cypriot origin with glomerulonephritis.
AB  - BACKGROUND: Complement is a key component of the innate immune system, and
      variation in genes that regulate its activation is associated with renal and
      other disease. We aimed to establish the genetic basis for a familial disorder of
      complement regulation associated with persistent microscopic haematuria,
      recurrent macroscopic haematuria, glomerulonephritis, and progressive renal
      failure. METHODS: We sought patients from the West London Renal and Transplant
      Centre (London, UK) with unusual renal disease and affected family members as a
      method of identification of new genetic causes of kidney disease. Two families of
      Cypriot origin were identified in which renal disease was consistent with
      autosomal dominant transmission and renal biopsy of at least one individual
      showed C3 glomerulonephritis. A mutation was identified via a genome-wide linkage
      study and candidate gene analysis. A PCR-based diagnostic test was then developed
      and used to screen for the mutation in population-based samples and in
      individuals and families with renal disease. FINDINGS: Occurrence of familial
      renal disease cosegregated with the same mutation in the complement factor H
      related protein 5 gene (CFHR5). In a cohort of 84 Cypriots with unexplained renal
      disease, four had mutation in CFHR5. Overall, we identified 26 individuals with
      the mutation and evidence of renal disease from 11 ostensibly unrelated kindreds,
      including the original two families. A mutant CFHR5 protein present in patient
      serum had reduced affinity for surface-bound complement. We term this renal
      disease CFHR5 nephropathy. INTERPRETATION: CFHR5 nephropathy accounts for a
      substantial burden of renal disease in patients of Cypriot origin and can be
      diagnosed with a specific molecular test. The high risk of progressive renal
      disease in carriers of the CFHR5 mutation implies that isolated microscopic
      haematuria or recurrent macroscopic haematuria should not be regarded as a benign
      finding in individuals of Cypriot descent. FUNDING: UK Medical Research Council
      and Wellcome Trust.

PMID- 20800272
TI  - A complement to kidney disease: CFHR5 nephropathy.

PMID- 20800273
TI  - Tissue engineered human tracheas for in vivo implantation.
AB  - Two years ago we performed the first clinical successful transplantation of a
      fully tissue engineered trachea. Despite the clinically positive outcome, the
      graft production took almost 3 months, a not feasible period of time for patients
      with the need of an urgent transplantation. We have then improved
      decellularization process and herein, for the first time, we completely describe
      and characterize the obtainment of human tracheal bioactive supports.
      Histological and molecular biology analysis demonstrated that all cellular
      components and nuclear material were removed and quantitative PCR confirmed it.
      SEM analysis revealed that the decellularized matrices retained the hierarchical
      structures of native trachea, and biomechanical tests showed that
      decellularization approach did not led to any influence on tracheal morphological
      and mechanical properties. Moreover immunohistological staining showed the
      preservation of angiogenic factors and angiogenic assays demonstrated that
      acellular human tracheal scaffolds exert an in vitro chemo-active action and
      induce strong in vivo angiogenic response (CAM analysis). We are now able to
      obtained, in a short and clinically useful time (approximately 3 weeks), a
      bioengineered trachea that is structurally and mechanically similar to native
      trachea, which exert chemotactive and pro-angiogenic properties and which could
      be successfully used for clinical tissue engineered airway clinical replacements.

PMID- 20800274
TI  - Enhancement of efficiencies of the cellular uptake and gene silencing of
      chitosan/siRNA complexes via the inclusion of a negatively charged poly(gamma
      glutamic acid).
AB  - Although advantageous for siRNA packing and protection, chitosan (CS)-based
      complexes may lead to difficulties in siRNA release once they arrive at the site
      of action, due to their electrostatic interactions. To assist the intracellular
      release of siRNA and thus enhance its effectiveness in gene silencing, we
      incorporated a negatively charged poly(gamma-glutamic acid) (gamma-PGA) into
      CS/siRNA complexes. The inclusion of gamma-PGA did not alter the complex
      formation ability between CS and siRNA; additionally, their cellular uptake was
      significantly enhanced. The results obtained in our molecular dynamic simulations
      indicate that the binding between CS and siRNA remained stable in the cytosol
      environment. In contrast, the compact structure of the ternary CS/siRNA/gamma-PGA
      complexes was unpacked; such a structural unpackage may facilitate the
      intracellular release of siRNA. In the gene silencing study, we found that the
      inclusion of gamma-PGA into complexes could significantly expedite the onset of
      gene knockdown, enhance their inhibition efficiency and prolong the duration of
      gene silencing. These findings may be attributed to the fact that there were
      significantly more CS/siRNA/gamma-PGA complexes internalized into the cells in
      company with their more rapid intracellular unpackage and release of siRNA when
      compared with their binary counterparts in the absence of gamma-PGA. The
      aforementioned results suggest that CS/siRNA/gamma-PGA complexes can be an
      efficient vector for siRNA transfection.

PMID- 20800275
TI  - The effect of strontium-substituted hydroxyapatite coating on implant fixation in
      ovariectomized rats.
AB  - This study was designed to investigate the effects of strontium-substituted
      hydroxyapatite coatings with 10 mol% Ca(2+) replaced by Sr(2+) (10% SrHA) on
      implant fixation in ovariectomized (OVX) rats. Coatings of HA and 10% SrHA were
      prepared on the surface of titanium implant using sol-gel dip methods, and then
      characterized by Scanning Electron Microscope, Atomic Force Microscope, X-ray
      diffraction, X-ray Photoemission Spectroscopy, and an automatic scratch tester.
      Twelve weeks after bilateral ovariectomy, twenty OVX rats accepted implant
      insertion in the proximal tibiae, half with HA-coated implants and the other half
      with 10% SrHA coated implants. After 12-week healing period, 10% SrHA coated
      implants revealed improved osseointegration compared to HA, with the bone area
      ratio and bone-to-implant contact increased by 70.9% and 49.9% in
      histomorphometry, the bone volume ratio and percent osseointegration by 73.7% and
      45.2% in micro-CT evaluation, and the maximal push-out force and ultimate shear
      strength by 107.2% and 132.9% in push out test. These results demonstrated that
      10% SrHA coatings could enhance implant osseointegration in OVX rats, and
      suggested the feasibility of using SrHA coatings to improve implant fixation in
      osteoporotic bone.

PMID- 20800276
TI  - An in vitro assessment of titanium functionalized with polysaccharides conjugated
      with vascular endothelial growth factor for enhanced osseointegration and
      inhibition of bacterial adhesion.
AB  - The long-term success of orthopedic implants may be compromised by defective
      osseointegration and bacterial infection. An effective approach to minimize
      implant failure would be to modify the surface of the implant to make it
      habitable for bone-forming cells and anti-infective at the same time. In this in
      vitro study, the surfaces of titanium (Ti) substrates were functionalized by
      first covalently grafting either dopamine followed by carboxymethyl chitosan
      (CMCS) or hyaluronic acid-catechol (HAC). Vascular endothelial growth factor
      (VEGF) was then conjugated to the polysaccharide-grafted surface. Antibacterial
      assay with Staphylococcus aureus (S. aureus) showed that the polysaccharide
      modified substrates significantly decrease bacterial adhesion. The CMCS
      functionalized Ti demonstrated better antibacterial property than the HAC
      functionalized Ti since CMCS is bactericidal while HA only inhibits the adhesion
      of bacteria without killing them. Osteoblast attachment, as well as alkaline
      phosphatase (ALP) activity and calcium deposition were enhanced by the
      immobilized VEGF on the polysaccharide-grafted Ti. Thus, Ti substrates modified
      with polysaccharides conjugated with VEGF can promote osteoblast functions and
      concurrently reduce bacterial adhesion. Since VEGF is also known to enhance
      angiogenesis, the VEGF-polysaccharide functionalized substrates will have
      promising applications in the orthopedic field.

PMID- 20800277
TI  - Miscibility of choline-substituted polyphosphazenes with PLGA and osteoblast
      activity on resulting blends.
AB  - The preparation of phosphazene tissue engineering scaffolds with bioactive side
      groups has been accomplished using the biological buffer, choline chloride. Mixed
      substituent phosphazene cyclic trimers (as model systems) and polymers with
      choline chloride and glycine ethyl ester, alanine ethyl ester, valine ethyl
      ester, or phenylalanine ethyl ester were synthesized. Two different synthetic
      protocols were examined. A sodium hydride mediated route resulted in
      polyphosphazenes with a low choline content, while a cesium carbonate mediated
      process produced polyphosphazenes with higher choline content. The phosphazene
      structures and physical properties were studied using multinuclear NMR,
      differential scanning calorimetry (DSC), and gel permeation chromatography (GPC)
      techniques. The resultant polymers were then blended with PLGA (50:50) or PLGA
      (85:15) and characterized by DSC analysis and scanning electron microscopy (SEM).
      Polymer products obtained via the sodium hydride route produced miscible blends
      with both ratios of PLGA, while the cesium carbonate route yielded products with
      reduced blend miscibility. Heterophase hydrolysis experiments in aqueous media
      revealed that the polymer blends hydrolyzed to near-neutral pH media (~5.8 to
      6.8). The effect of different molecular structures on cellular adhesion showed
      osteoblast proliferation with an elevated osteoblast phenotype expression
      compared to PLGA over a 21-day culture period.

PMID- 20800278
TI  - Tissue-engineered conduit using urine-derived stem cells seeded bacterial
      cellulose polymer in urinary reconstruction and diversion.
AB  - The objective of this study was to generate bacterial cellulose (BC) scaffolds
      seeded with human urine-derived stem cells (USC) to form a tissue-engineered
      conduit for use in urinary diversion. Microporous BC scaffolds were synthesized
      and USC were induced to differentiate into urothelial and smooth muscle cells
      (SMC). Induced USC (10(6) cells/cm(2)) were seeded onto BC under static and 3D
      dynamic (10 or 40 RPM) conditions and cultured for 2 weeks. The urothelial cells
      and SMC derived from USC formed multilayers on the BC scaffold surface, and some
      cells infiltrated into the scaffold. The urothelium derived from USC
      differentiation expressed urothelial markers (uroplakin Ia and AE1/AE3) and the
      SMC expressed SMC markers (alpha-smooth muscle actin and desmin). In addition,
      USC/BC scaffold constructs were implanted into athymic mice, and the cells were
      tracked using immunohistochemical staining for human nuclear antigen. In vivo,
      the cells appeared to differentiate and express urothelial and SMC markers. In
      conclusion, porous BC scaffolds allow 3 dimensional growth of USC, leading to
      formation of a multilayered urothelium and cell-matrix infiltration. Thus, cell
      seeded BC scaffolds hold promise for use in tissue-engineered urinary conduits
      for urinary reconstruction.

PMID- 20800279
TI  - Modulating Notch signaling to enhance neovascularization and reperfusion in
      diabetic mice.
AB  - Diabetes can diminish the responsiveness to angiogenic factors (e.g., VEGF)
      important for wound healing and the treatment of ischemic diseases, and this
      study investigated the hypothesis that this effect can be reversed by altering
      Notch signaling. Aortic endothelial cells (ECs) isolated from diabetic mice
      demonstrated reduced sprouting capability in vitro, but adding a Notch inhibitor
      (DAPT) led to cell-density and VEGF-dose dependent enhancement of proliferation,
      migration and sprouting, in both 2-D and 3-D cultures, as compared to VEGF alone.
      The in vivo effects of VEGF and DAPT were tested in the ischemic hind limbs of
      diabetic mice. Combining VEGF and DAPT delivery resulted in increased blood
      vessel density (~150%) and improved tissue perfusion (~160%), as compared to VEGF
      alone. To examine if DAPT would interfere with vessel maturation, DAPT was also
      delivered with a combination of VEGF and platelet derived growth factor (PDGF).
      DAPT and PDGF did not interfere with the effects of the other, and highly
      functional and mature networks of vessels could be formed with appropriate
      delivery. In summary, modulating Notch signaling enhances neovascularization and
      perfusion recovery in diabetic mice suffering from ischemia, suggesting this
      approach could have utility for human diabetics.

PMID- 20800280
TI  - Bioreactor based engineering of large-scale human cartilage grafts for joint
      resurfacing.
AB  - Apart from partial or total joint replacement, no surgical procedure is currently
      available to treat large and deep cartilage defects associated with advanced
      diseases such as osteoarthritis. In this work, we developed a perfusion
      bioreactor system to engineer human cartilage grafts in a size with clinical
      relevance for unicompartmental resurfacing of human knee joints (50 mm diameter *
      3 mm thick). Computational fluid dynamics models were developed to optimize the
      flow profile when designing the perfusion chamber. Using the developed system,
      human chondrocytes could be seeded throughout large 50 mm diameter scaffolds with
      a uniform distribution. Following two weeks culture, tissues grown in the
      bioreactor were viable and homogeneously cartilaginous, with biomechanical
      properties approaching those of native cartilage. In contrast, tissues generated
      by conventional manual production procedures were highly inhomogeneous and
      contained large necrotic regions. The unprecedented engineering of human
      cartilage tissues in this large-scale opens the practical perspective of grafting
      functional biological substitutes for the clinical treatment for extensive
      cartilage defects, possibly in combination with surgical or pharmacological
      therapies to support durability of the implant. Ongoing efforts are aimed at
      integrating the up-scaled bioreactor based processes within a fully automated and
      closed manufacturing system for safe, standardized, and GMP compliant production
      of large-scale cartilage grafts.

PMID- 20800282
TI  - Uptake and biochemical responses of mussels Mytilus galloprovincialis exposed to
      sublethal nickel concentrations.
AB  - In the present study, mussel (Mytilus galloprovincialis) digestive gland
      oxidative stress biomarkers and detoxification responses to acute exposure to
      nickel (Ni) were investigated. Mussels were exposed to two sublethal
      concentrations of Ni (135 MUg/L per animal (2.5 MUM) and 770 MUg/L per animal (13
      MUM)) for 24, 48, 72, 96 h and 8 days. Following biological responses were
      measured: (1) glutathione S-transferase (GST) activity as a phase II conjugation
      enzyme, (2) catalase activity as antioxidant response, (3) malondialdehyde
      accumulation (MDA) as lipid peroxydation marker and metallothionein as specific
      response to metals exposure. The cholinergic system was evaluated using the
      acetylcholinesterase activity (AChE). Moreover, Ni uptakes during the exposure
      periods were assessed and the uptake rate constant determined. A correlation
      matrix (CM) between the investigated biomarkers and a principal component
      analysis (PCA) were achieved for the two tested concentrations. The Ni-uptake
      constant was higher in animals exposed to the lowest concentration. The CM and
      the PCA showed a time-dependent effect of the Ni exposure on the investigated
      biomarkers being more pronounced in animals exposed to the highest Ni
      concentration. While AChE showed a significant increase after 48 h and a further
      return to control values in the lowest concentration, it was drastically
      maintained inhibited in the highest concentration. Our data provided clues about
      the occurrence of different toxicokinetics and toxicodynamics of two Ni sublethal
      concentrations in an ecologically relevant organism.

PMID- 20800283
TI  - Daptomycin as successful treatment for a refractory case of prosthetic valve
      endocarditis because of methicillin-sensitive Staphylococcus aureus.
AB  - We report on an intravenous drug user who presented with methicillin-sensitive
      Staphylococcus aureus bacteremia and endocarditis of a prosthetic tricuspid
      valve, with a 4-cm vegetation refractory to standard antibiotic treatment. The
      patient responded to intravenous daptomycin therapy clinically and
      microbiologically, despite an absence of surgical intervention.

PMID- 20800281
TI  - Evidence that low-grade systemic inflammation can induce islet dysfunction as
      measured by impaired calcium handling.
AB  - In obesity and the early stages of type 2 diabetes (T2D), proinflammatory
      cytokines are mildly elevated in the systemic circulation. This low-grade
      systemic inflammation exposes pancreatic islets to these circulating cytokines at
      much lower levels than seen within the islet during insulitis. These low-dose
      effects have not been well described. We examined mouse islets treated overnight
      with a low-dose cytokine combination commonly associated with inflammation (TNF
      alpha, IL-1 beta, and IFN-gamma). We then examined islet function primarily using
      intracellular calcium ([Ca(2+)](i)), a key component of insulin secretion and
      cytokine signaling. Cytokine-treated islets demonstrated several features that
      suggested dysfunction including excess [Ca(2+)](i) in low physiological glucose
      (3mM), reduced responses to glucose stimulation, and disrupted [Ca(2+)](i)
      oscillations. Interestingly, islets taken from young db/db mice showed similar
      disruptions in [Ca(2+)](i) dynamics as cytokine-treated islets. Additional
      studies of control islets showed that the cytokine-induced elevation in basal
      [Ca(2+)](i) was due to both greater calcium influx through L-type-calcium
      channels and reduced endoplasmic reticulum (ER) calcium storage. Many of these
      cytokine-induced disruptions could be reproduced by SERCA blockade. Our data
      suggest that chronic low-grade inflammation produces circulating cytokine levels
      that are sufficient to induce beta-cell dysfunction and may play a contributing
      role in beta-cell failure in early T2D.

PMID- 20800284
TI  - Implementation of an evidence-based modified therapeutic community: staff and
      resident perspectives.
AB  - The widespread successful implementation of evidence-based practices (EBPs) into
      community substance abuse settings require a thorough understanding of
      practitioner and client attitudes toward these approaches. This paper presents
      the first that we know of a qualitative study that explores staff and resident
      experience of the change process of a therapeutic community to an evidence-based
      modified therapeutic community for homeless individuals with co-occurring
      substance abuse and mental illness disorders. The sample consists of 20
      participants; 10 staff and 10 residents. Interviews were conducted at the agency,
      recorded and transcribed verbatim. Transcripts were organized and coded from a
      grounded theory perspective. Themes and patterns of staff and resident experience
      were identified. The change in program structure from TC to MTC were perceived by
      staff as efforts to accommodate the particular needs of the homeless individuals
      with mental and substance abuse disorders and feeling they were inadequately
      prepared with inadequate resources to facilitate a successful transition.
      Participant descriptions were described in terms of loss of structure, loss of
      peers and being helped. Findings have potential to shape implementation of
      evidence-based practices in community substance abuse treatment.

PMID- 20800285
TI  - The clinical validity and reliability of the Brief Infant-Toddler Social and
      Emotional Assessment (BITSEA).
AB  - This study investigates the construct validity and reliability of the Brief
      Infant-Toddler Social and Emotional Assessment (BITSEA) in a psychiatric clinical
      sample of toddlers. The sample consisted of a psychiatric clinical sample (N=112)
      (male, n=79; female, n=33) of toddlers (12- to 42-months old). Both mothers and
      fathers completed the BITSEA and mothers completed the Child Behavior Checklist
      2/3 (CBCL). Children and their parents were administered a comprehensive
      psychiatric evaluation. Parents were also given the Autistic Behavior Checklist
      (AuBC) and the Aberrant Behavior Checklist-Community (ABC). The internal
      consistency of BITSEA scores was good to excellent for both parents. The
      BITSEA/Problem (P) scores were significantly correlated with Internalizing,
      Externalizing and Total Problem scores of the CBCL, all subscores of ABC and
      total score of AuBC. The BITSEA/Competence (C) scores were significantly
      inversely correlated with ABC total and AuBC lethargy scores. With respect to a
      community sample, BITSEA/P scores were significantly higher in the disruptive
      behavior disorder (DBD) and anxiety/depression (Anx/Dep) groups and BITSEA/C
      scores were significantly lower in the autism group. These results support the
      reliability and validity of the BITSEA as a screening tool that may be employed
      in primary health care services and in psychiatric clinical settings for
      assessing social-emotional/behavioral problems and delays in competence in
      infants and toddlers.

PMID- 20800286
TI  - Brazelton Neonatal Behavioral Assessment Scale: a psychometric study in a
      Portuguese sample.
AB  - BACKGROUND: The Neonatal Behavioral Assessment Scale (NBAS, Brazelton & Nugent,
      1995) is an instrument conceived to observe the neonatal neurobehavior. Data
      analysis is usually performed by organizing items into groups. The most widely
      used data reduction for the NBAS was developed by Lester, Als, and Brazelton
      (1982). OBJECTIVE: Examine the psychometric properties of the NBAS items in a
      sample of 213 Portuguese infants. METHOD: The NBAS was performed in the first
      week of infant life (3 days+/-2) and in the seventh week of life (52 days+/-5).
      RESULTS: Principal component analyses yielded a solution of four components
      explaining 55.13% of total variance. Construct validity was supported by better
      neurobehavioral performance of 7-week-old infants compared with 1-week-old
      infants. CONCLUSION: Changes in the NBAS structure for the Portuguese sample are
      suggested compared to Lester factors in order to reach better internal
      consistency of the scale.

PMID- 20800287
TI  - Differential impairments in emotion face recognition in postpartum and
      nonpostpartum depressed women.
AB  - BACKGROUND: Though potential differences in postpartum and nonpostpartum major
      depression have major implications for the etiology and treatment of both
      disorders, these differences have not been clearly delineated. Emotion theory
      presents a potentially important framework for understanding these differences.
      METHODS: The current study examined the performance of 65 postpartum depressed,
      65 nonpostpartum depressed, and 65 healthy control women on two facial
      recognition tasks. RESULTS: Postpartum and nonpostpartum participants performed
      worse on the recognition of emotions of happiness and fear when compared to
      controls on both tasks. Participants with postpartum depression showed a greater
      impairment on both disgust and anger when compared to participants with
      nonpostpartum depression; participants with nonpostpartum depression showed
      greater impairment on happiness when compared to postpartum depression.
      CONCLUSION: Postpartum and nonpostpartum depression may impair facial expression
      recognition differently. Results are discussed in terms of limitations and
      clinical implications.

PMID- 20800288
TI  - Alexithymia in personality disorders: correlations with symptoms and
      interpersonal functioning.
AB  - Impairment in the ability to recognize and make sense of emotions has been
      hypothesized to be present in a sub-sample of people suffering from personality
      disorder (PD). In particular it is possible that difficulty recognizing and
      expressing feelings, or alexithymia, is related to many of the symptoms and
      problems in making sense of social interactions which are hallmarks of PD. In
      this study we measured levels of alexithymia with the Toronto Alexithymia Scale
      20 and explored its correlations with the overall presence of PD and different PD
      diagnoses, symptoms, and interpersonal difficulties. Results were largely
      consistent with the hypothesis. Higher levels of alexithymia were related to high
      levels of global psychopathology and with dysfunctional representation of
      interpersonal relations. A sub-sample of patients, mostly suffering from
      avoidant, dependent, passive-aggressive and depressive PD, had alexithymic
      features and, in particular reported difficulties describing their feelings to
      others. A patient with cluster B PD featured no alexithymia. Implications of this
      study for future research and treatment are discussed.

PMID- 20800289
TI  - Reality monitoring and its association with social functioning in schizophrenia.
AB  - Reality monitoring, or the ability to discriminate internal from external
      information present in short-term memory, is relevant in the study of
      schizophrenia. Previous research has linked monitoring impairments with psychotic
      symptoms and certain forms of communication disturbance. The focus of the present
      study was to test the hypothesis that there would be specific relationships
      between reality monitoring in patients with schizophrenia and current and pre
      morbid social functioning, beyond the effects of general verbal ability. Fifty
      outpatients with schizophrenia or schizoaffective disorder were assessed for
      internal/external reality monitoring deficits, general verbal intelligence, and
      both current and pre-morbid social functioning. Associations between these
      variables were assessed. Exploratory analyses also were conducted to determine
      whether specific types of reality monitoring errors were related to social
      functioning. Results showed that (a) overall accuracy in reality monitoring was
      related to pre-morbid social functioning beyond the effects of verbal ability,
      (b) sensitivity to old versus new information in reality monitoring was related
      to current social functioning, and (c) a say-report-think reality monitoring
      error was significantly associated with pre-morbid social functioning. The
      results support the hypothesis of an association between reality monitoring
      sensitivity and social functioning.

PMID- 20800290
TI  - Effects of feed-borne Fusarium mycotoxins and an organic mycotoxin adsorbent on
      immune cell dynamics in the jejunum of chickens infected with Eimeria maxima.
AB  - An experiment was conducted to explore the effects of Fusarium mycotoxins, common
      animal feed contaminants, on intestinal immune responses to coccidia (Eimeria) in
      chickens. Effects of feed-borne Fusarium mycotoxins and a polymeric glucomannan
      mycotoxin adsorbent (GMA) on immune cell populations were studied in the jejunum
      of broiler breeder pullets using an Eimeria maxima infection model. Birds were
      fed a control diet, a diet naturally contaminated with Fusarium mycotoxins,
      contaminated diet plus 0.2% GMA, or control diet plus 0.2% GMA. Contaminated
      diets contained up to 6.5MUg/g deoxynivalenol (DON), 0.47MUg/g 15-acetyl-DON and
      0.73MUg/g zearalenone. Birds received a primary oral inoculation (1000
      oocysts/bird) with E. maxima USDA strain 68 at 2 weeks of age and a secondary
      oral inoculation (30,000 oocysts/bird) with the same strain at 4 weeks of age.
      Diet-related differences in CD4(+) cell, CD8(+) cell and macrophage recruitment
      pattern into the jejunum were observed following both the primary and secondary
      infections. It was concluded that feed-borne Fusarium mycotoxins and GMA have the
      potential to modulate immune response to coccidial infections.

PMID- 20800292
TI  - Sex and autoantibody titers determine the development of neuropsychiatric
      manifestations in lupus-prone mice.
AB  - Emotional disturbances are among the most common neuropsychiatric manifestations
      of SLE, a systemic autoimmune disease with a strong female predominance. In this
      study, we evaluated young MRL/lpr mice, directly comparing males and females.
      MRL/lpr females exhibited significant depression as early as 5 weeks (at which
      time elevated levels of autoantibodies were already present), as compared to
      MRL/lpr males, where depression was noted only at 18 weeks. Depression was
      significantly correlated with autoantibodies against nuclear antigens, NMDA
      receptor, and ribosomal P. Our results are consistent with a primary role of
      autoantibodies in the pathogenesis of early neuropsychiatric deficits in this
      lupus model, which translate into gender-based differences in clinical phenotype.

PMID- 20800291
TI  - Acute mastitis induces upregulation of expression of plasminogen activator
      related genes by blood monocytes and neutrophils in dairy ewes.
AB  - The main objective of the present study was to examine whether genes implicated
      in the plasminogen activating cascade: urokinase-type plasminogen activator (u
      PA), u-PA receptor (u-PAR) and plasminogen activator inhibitors type 1 (PAI-1)
      and type 2 (PAI-2) are expressed in a differential manner in ovine blood
      monocytes and neutrophils obtained from healthy and mastitic dairy ewes. A total
      of 48 blood samples were collected from 8 healthy and 8 mastitic dairy ewes over
      a period of 3 weeks. Streptococcus agalactiae was detected in milk samples
      isolated from mastitic animals. Results indicated that expression of all four
      genes was very low in monocytes and neutrophils isolated from healthy animals. In
      contrast, there was a 2- to 5-fold increase (P<0.05) in expression of all four
      genes in monocytes and an 18- to 38-fold increase (P<0.01) in neutrophils
      isolated from mastitic animals. In conclusion, upregulation of expression of u-PA
      and u-PAR by monocytes and neutrophils is probably related to the rapidity of
      migration of these cells towards the mammary gland, while the upregulation of PAI
      1 and PAI-2 is a rather enigmatic observation and it is probably related to the
      successful localization of the infection.

PMID- 20800293
TI  - Language development in children after receiving bilateral cochlear implants
      between 5 and 18 months.
AB  - OBJECTIVE: The objective of this study was to examine receptive and expressive
      language development in children who received simultaneous bilateral cochlear
      implants (CIs) between 5 and 18 months of age and to compare the results with
      language development in chronologically age-matched children with normal hearing.
      METHODS: The study used a prospective, longitudinal matched-group design. Data
      were collected in a clinical setting at postoperative cochlear implant check-ups
      after 3, 6, 9, 12, 18, 24, 36, and 48 months of implant use. The sample included
      42 children: 21 cochlear implant users and 21 with normal hearing, matched
      pairwise according to gender and chronological age. Communication assessments
      included the LittlEARS questionnaire, the Mullen Scale of Early Learning, and the
      Minnesota Child Development Inventory. RESULTS: The cochlear implant users'
      hearing function according to LittlEARS was comparable to that of normal-hearing
      children within 9 months post-implantation. The mean scores after 9 and 12 months
      were 31 and 33, respectively in the prelingually deaf versus 31 and 34 in the
      normal-hearing children. The children's receptive and expressive language scores
      showed that after 12-48 months with cochlear implants, 81% had receptive language
      skills within the normative range and 57% had expressive language skills within
      the normative range. The number of children who scored within the normal range
      increased with increasing CI experience. CONCLUSIONS: The present study showed
      that prelingually deaf children's ability to develop complex expressive and
      receptive spoken language after early bilateral implantation appears promising.
      The majority of the children developed language skills at a faster pace than
      their hearing ages would suggest and over time achieved expressive and receptive
      language skills within the normative range.

PMID- 20800294
TI  - Expanded protocol of orofacial myofunctional evaluation with scores: Validity and
      reliability.
AB  - OBJECTIVE: Clinical evaluation of the stomatognathic system is indispensable for
      the diagnosis of orofacial myofunctional disorders. In order to obtain a more
      precise diagnosis, the protocol of orofacial myofunctional evaluation with scores
      (OMES protocol) (Int. J. Pediatr. Otorhinolaryngol. 72 (2008) 367-375) was
      expanded in terms of number of items and scale amplitude. The proposal of this
      study is to describe the expanded OMES protocol (OMES-E) for the evaluation of
      children. Validity of the protocol, reliability of the examiners and agreement
      between them were analyzed, as also were the sensitivity, specificity and
      predictive values of the instrument. METHODS: The sample consisted of
      videorecorded images of 50 children, 25 boys (mean age=8.4 years, SD=1.8) and 25
      girls (mean age=8.2 years, SD=1.7) selected at random from 200 samples. Three
      speech therapists prepared for orofacial myofunctional evaluation participated as
      examiners (E). The OMES and OMES-E protocols were used for evaluation on
      different days. E1 evaluated all images, E2 analyzed children with recordings
      from 1 to 25 and E3 analyzed children with recordings from 26 to 50. The validity
      of OMES-E was analyzed by comparing the instrument to the OMES protocol using the
      Pearson correlation test complemented with the split-half reliability test
      (p<0.05). The linear weighted Kappa coefficient of agreement (Kw'), the
      sensitivity, specificity and predictive values and the prevalence of OMD were
      calculated. RESULTS: There was a statistically significant correlation between
      the OMES and OMES-E protocols (0.79>r<0.94, p<0.01) and a significant test-retest
      correlation with the OMES-E (0.75>r<0.86, p<0.01), with a reliability range of
      0.86-0.93. The correlation and reliability coefficients between examiners were:
      E1*E2 (r=0.74, 0.84), E1*E3 (r=0.70, 0.83) (p<0.01). Kw' coefficients with
      moderate and good strength predominated. The OMES-E protocol presented mean
      sensitivity=0.91, specificity=0.77, positive predictive value=0.87 and negative
      predictive value=0.85. The mean prevalence of OMD was 0.58. CONCLUSION: The OMES
      E protocol is valid and reliable for orofacial myofunctional evaluation.

PMID- 20800295
TI  - Propranolol in the therapeutic strategy of infantile laryngotracheal hemangioma:
      A preliminary retrospective study of French experience.
AB  - OBJECTIVE: Preliminary assessment of the efficacy of propranolol on subglottic
      hemangioma in children on a nation-wide scale. METHODS: Multicentric,
      retrospective study of clinical files of 14 children; pre- and post-treatment
      endoscopies. RESULTS: Mean age at diagnosis was 2.3 (0.7-4) months. Mean
      percentage of airway obstruction was 68% (15-90) before propranolol introduction.
      Propranolol was started at 5.2 (0.7-16) months of age. This treatment was
      effective in all cases with a mean regression of the stenosis to 22% after 2
      weeks and 12% after 4 weeks. Other medical treatments (steroids) could be
      stopped. In one patient, a side effect of propranolol motivated the switch to
      another beta-blocker. In four patients, treatment was stopped after 5.2 (1-10)
      months with a relapse in 2 (50%) cases. One of these two patients developed a
      resistance to propranolol and required a surgical procedure by external approach.
      CONCLUSION: This preliminary nation-wide survey confirms propranolol high
      effectiveness against airways' localization of infantile hemangiomas. Propranolol
      also allows alleviation or cut-off of previous medical treatments. However,
      recurrences are possible after early treatment interruption.

PMID- 20800296
TI  - Comment on "Prevalence and risk factors for allergic rhinitis in primary school
      children in Budapest" by Monika Sultesz et al. [Int. J. Pediatr.
      Otorhinolaryngol. 74 (2010) 503-509].

PMID- 20800297
TI  - Laser division of congenital complete tracheal rings.
AB  - Congenital complete tracheal rings are a rare and life threatening problem in
      young children and they are often challenging to manage. Whilst historically
      associated with high mortality rates increasing experience with this tracheal
      pathology has led to much improved survival rates and slide tracheoplasty has
      become the treatment of choice. We present 3 cases in which an open procedure was
      not deemed possible and they underwent laser division (CO2, KTP) of their
      complete rings. Two patients subsequently required stent insertion. All patients
      are alive and well at a mean follow up of 3 years and 5 months. Whilst laser
      division of complete tracheal rings has only been described in a small number of
      cases it may provide an alternative approach in patients who are not able to
      undergo an open procedure or in an emergency situation.

PMID- 20800298
TI  - Long term results of ossiculoplasties with partial and total titanium Vario Kurz
      prostheses in children.
AB  - OBJECTIVE: To assess and compare the efficacy of the Kurz titanium prostheses for
      total or partial ossicular reconstruction in children. PATIENTS AND METHODS:
      Retrospective chart review was performed for 71 consecutive children who
      underwent 74 ossicular reconstructions with Kurz prostheses between December 1999
      and October 2007 (27 PORP and 47 TORP). Audiological parameters using four
      frequency averages (0.5, 1, 2 and 4 kHz) were assessed pre- and postoperatively.
      Clinical and audiometric follow-up times were respectively 33+/-18.6 and 30+/
      17.7 months (mean+/-SD). RESULTS: Fifty-two percent of all patients achieved an
      air bone gap (ABG) <=20 dB, 53.8% in the PORP group and 51.1% in the TORP group.
      The improvement of the mean ABG was 13.3 dB, 9.4 dB for PORP and 14.6 dB for
      TORP. Overall mean pure tone averages improved 13.2+/-1.8 dB (mean+/-SEM) with
      10+/-2.7 dB for PORP and 15+/-2.4 dB for TORP. The sensory neural hearing loss
      rate was 1.4% (one TORP) and the extrusion rate was 2.7% (n=2/74). CONCLUSION:
      The success rate (ABG<=20 dB) and the pure tone averages were not different
      between PORP and TORP. Kurz titanium ossicular prostheses offer high
      biocompatibility and high stability with low complication rates in pediatric
      ossicular reconstruction.

PMID- 20800299
TI  - Management and outcome of pediatric skull base fractures.
AB  - OBJECTIVE: The management of skull base fractures in the pediatric age group
      continues to be a major challenge even for experienced multidisciplinary teams.
      This retrospective study was undertaken at a tertiary care academic hospital to
      evaluate the management and outcome of pediatric skull base fractures. METHODS:
      Retrospective analysis covering a period of 13.5 years (from 1996 to 2009) and 63
      patients (mean age 10.7 years; range 1-18 years) was performed. RESULTS: A road
      traffic accident was the most frequent etiological factor (38%). The most common
      skull base fracture type was temporal bone fracture (64%). Longitudinal temporal
      fractures were observed in 45% and transversal in 23% of these patients; in 10
      cases (25%) the fracture was comminuted or mixed type. A fracture involving the
      spheno-ethmoidal complex was the second most common type of basilar skull
      fracture (41%) followed by fracture through the orbital bone (35%). Forty-three
      percent of the patients had a concomitant intracranial injury. Early neurological
      deficits were diagnosed in 21 patients (33%) and 10 patients (16%) had permanent
      neurological deficits. One patient died after 1 week of intensive care treatment.
      Fifty-four patients (86%) were discharged home and 8 patients (13%) were
      discharged for further rehabilitation. Glasgow Coma Scale score of 8 or lower
      correlated with moderate to poor outcome. CONCLUSIONS: We conclude that skull
      base fracture is a rare injury in childhood. Mortality is uncommon, but this
      trauma is commonly associated with intracranial injury. Early neurological
      deficits are caused by traumatic brain injury and were observed in one-third of
      the patients. However, only less than one-sixth suffered from permanent
      neurological or neuropsychiatric disorders.

PMID- 20800300
TI  - Revision of the ADA-classification of diabetes mellitus type 2 (DMT2): the
      importance of maturity onset diabetes (MOD), and senile diabetes (DS).
AB  - The changing social and economic conditions and the increase of the life span
      induced a progressive increase of the general prevalence of DMT2, particularly in
      the elderly population of the highly evoluted countries. Up to now 18 genetic
      loci have been identified, each of them consisting of several single nucleotide
      polymorphisms (SNPs). The evidence that the DMT2 is regulated by a high number of
      genes, demonstrate the pathogenetic complexity of this disease. The onset of
      diabetes mellitus (DM) in medium age is a consequence of the breakdown of the
      glycemic homeostasis in correlation with the genetic factors, such as the
      variants of the TCF7L2, obesity, etc., and the environmental factors, such as the
      life-style, the evolution of chronic-degenerative diseases, etc. In case of DM
      that onsets in old age we have to add the deterioration of the anti-aging defense
      mechanisms, characterized by the antagonistic action of the genes of longevity
      and aging. One can observe several clinical and therapeutic differences;
      therefore, the authors of this review propose the reinsertion of three forms into
      the DMT2 correlated with the age of onset and with the actual age of the
      subjects: the maturity onset diabetes (MOD), the maturity onset diabetes in
      elderly (MODE), and the senile diabetes (DS).

PMID- 20800301
TI  - Economic effect of bovine abortion syndrome in commercial dairy herds in Southern
      Chile.
AB  - Bovine abortion is a limiting factor for dairy business, as it decreases milk
      production and the potential, number of herd replacements, increases feeding and
      medical treatment costs, increases the number of artificial inseminations to
      obtain a calf as well as culling rates of cows. An estimation of the economic
      impact of abortion in dairy farms in Chile is not available yet. The aim of this
      study was to estimate the economic consequences of bovine abortion syndrome (BAS)
      in dairy cows from Chile. A stochastic model was proposed to evaluate the cost of
      an abortion on a yearly basis to include variability in cost and income by dairy
      and by year. The marginal total net revenue (DeltaTNR) for a typical, lactation
      was obtained by the calculating the difference between total revenues (retail
      milk and calf sales) and total expenses (production cost (cows, feeding, labor,
      health) plus administrative and, general costs) for lactation with and without
      abortion. Production data were obtained from a retrospective study of 127 dairy
      herds located in southern Chile between 2000 and 2006. Milk production from cows
      with and without abortion was estimated by a mixed model using milk test day
      data. Production cost and prices paid to farmers were obtained from service
      company records (TODOAGRO S.A.). Cost and income value was corrected for
      inflation and expressed in the values from 2006. In addition, a separate analysis
      for different parities (1, 2, 3 or more) was performed. Distributions for the
      stochastic variables were obtained by fitting distributions from our database
      using @Risk. The stochastic variables included in the analysis were all related
      to income, feeding, depreciation, health, Artificial Insemination and general
      costs like fuel, salaries, taxes, etc. There was a high probability (89.20%) of a
      negative DeltaTNR in lactations with abortion for overall, parities, with a mean
      loss of $ -143.32. Stratifying by parity, the predicted mean of the distribution
      for DeltaTNR in each parity (1, 2, 3 or more) was also negative and the
      probability of a negative DeltaTNR was 89.40%, 95.30% and 97.00%, respectively,
      but differs between them (p<0.05). For parity 1, mean DeltaTNR was $ -120.92,
      parity 2 $ -116.35 and for parities >=3 it was $ -132.26 and the mean was
      statistically different from the others (p<0.05). The age of culled cows was the
      input variable most correlated with TNR and dairy production was the second.
      However, the sale price of milk resulted in a low correlation with abortion cost.

PMID- 20800302
TI  - Platform technologies for tubular organ regeneration.
AB  - As a result of recent successes in regenerative medicine approaches to
      engineering multiple disparate tubular organs, methodology commonalities are
      emerging. Principal themes include the importance of a biodegradable scaffold
      seeded with a population of smooth muscle cells. Such composites trigger a
      regenerative response following in vivo implantation, resulting in de novo
      organogenesis. In this review, we examine bladder regeneration as a foundational
      platform technology to highlight key principles applicable to the regeneration of
      any tubular organ, and illustrate how these general concepts underlie current
      strategies to regenerate components of gastrointestinal, vascular, pulmonary and
      genitourinary systems. We focus on identifying the elements of this platform that
      have facilitated the transition of tubular organ regeneration from academic proof
      of-concept to commercial viability.

PMID- 20800303
TI  - Potential of Arabidopsis systems biology to advance the biofuel field.
AB  - Plant biomass is a renewable and potentially sustainable resource for the
      production of liquid biofuels and a multitude of bio-based materials. To tailor
      plants for biofuel production, a powerful gene discovery program targeted to cell
      wall recalcitrance genes is needed. In parallel, a system is required that
      reveals the pleiotropic effects of gene modifications and that delivers the
      fundamental knowledge necessary for successful gene stacking. In our opinion,
      these objectives can be pioneered through a systems biology approach in
      Arabidopsis. We develop our ideas with a focus on the lignin biosynthetic
      pathway, because lignin is among the most important factors determining cell wall
      recalcitrance.

PMID- 20800304
TI  - Curved motions in horizontal and vertical orientations.
AB  - A consideration of handwriting demonstrates that motions can be remarkably
      constant, even when performed with different effectors. Nevertheless, the
      transposition of writing from horizontal to vertical orientations, as occurs when
      writing on blackboards, poses additional problems for the constraint of movement.
      Motions in horizontal and vertical planes potentially challenge the mechanisms
      responsible for motor constancy. Gravitational fields impose different
      accelerative forces on vertical (up/down) compared with horizontal (left/right)
      motions. A 1/3 power law linking tangential velocity and radius of curvature is
      sometimes invoked to explain how equivalent motions can be performed by different
      effectors. To evaluate the operation of the power law when movements are
      performed in different orientations, 12 participants drew ellipses in horizontal
      and vertical planes at about 1 or 2 Hz. Mean tangential velocity, radius of
      curvature and the strength of the 1/3 power law were analyzed. The power law was
      strongest for curved motions at faster speeds. The power law was weakest at
      slower speeds in the vertical orientation. As participants controlled their
      movement periodicity, this placed tighter constraints upon curvature in the
      vertical orientations than the horizontal orientations. Speed of motion had a
      greater effect upon curvatures in the horizontal than the vertical orientation.
      The data offer insights into variations in the strength of the power law under
      different orientations, and indicate a limited role for the 1/3 power law in
      motor constancy.

PMID- 20800305
TI  - Fulminant type 1 diabetes mellitus with rhabdomyolysis: have we overlooked the
      situation?
AB  - Fulminant type 1 diabetes mellitus (FT1DM) is characterized as remarkably abrupt
      onset and severe metabolic disorder. Prominent derangement of serum electrolytes
      was frequently observed, which could be associated with rhabdomyolysis. But the
      issue was not touched upon in most of the articles concerning FT1DM. Herein, we
      reported 2 cases. Since the clinical features of rhabdomyolysis vary, and
      creatine kinase levels are not routinely tested in young patients, the situation
      of rhabdomyolysis associated with FT1DM may be overlooked.

PMID- 20800306
TI  - Relapsing features of bile salt export pump deficiency after liver
      transplantation in two patients with progressive familial intrahepatic
      cholestasis type 2.
AB  - BACKGROUND & AIMS: PFIC2 is caused by mutations in ABCB11 encoding BSEP. In most
      cases affected children need liver transplantation that is thought to be
      curative. We report on two patients who developed recurrent normal GGT
      cholestasis mimicking primary BSEP disease, after liver transplantation. METHODS:
      PFIC2 diagnosis was made in infancy in both patients on absence of canalicular
      BSEP immunodetection and on ABCB11 mutation identification. Liver transplantation
      was performed at age 9 (patient 1) and 2.8 (patient 2) years without major
      complications. Cholestasis with normal GGT developed 17 and 4.8years after liver
      transplantation, in patient 1 and patient 2, respectively, during an
      immunosuppression reduction period. RESULTS: Liver biopsies showed canalicular
      cholestasis, giant hepatocytes, and slight lobular fibrosis, without evidence of
      rejection or biliary complications. An increase in immunosuppression resulted in
      cholestasis resolution in only one patient. Both patients developed atrial
      fibrillation, and one melanonychia. The newborn of patient 1 developed transient
      neonatal normal GGT cholestasis. Immunofluorescence staining of normal human
      liver sections with patient's sera, collected at the time of cholestasis, and
      using an anti-human IgG antibody to detect serum antibodies, showed reactivity to
      a canalicular epitope, likely to be BSEP. Indeed, Western blot analysis showed
      that patient 2 serum recognized rat Bsep. CONCLUSIONS: Allo-immune mediated BSEP
      dysfunction may occur after liver transplantation in PFIC2 patients leading to a
      PFIC2 like phenotype. Extrahepatic features and/or offspring transient neonatal
      cholestasis of possible immune mediated mechanisms, may be associated. Increasing
      the immunosuppressive regimen might be an effective therapy.

PMID- 20800307
TI  - Retransplantation in patients with hepatitis C recurrence after liver
      transplantation.
AB  - Hepatitis C virus (HCV) infection recurs universally after liver transplantation
      (LT) and fibrosis progression is accelerated in the graft. Retransplantation (RT)
      is the only therapeutic option to achieve long-term survival in patients with
      decompensated cirrhosis after LT. Patient and graft survival rates after RT are
      inferior to those after primary LT. It is generally accepted that severe
      hepatitis C recurrence (cholestatic hepatitis) and forms with rapid fibrosis
      progression have a poor survival after RT. However, it is not clear whether rapid
      fibrosis progression in the first graft will be followed by the same rate of
      fibrosis progression in the second graft. The use of prognostic scores as
      screening tools has shown an improvement in survival in HCV-infected patients
      after RT, reaching similar survival rates as those obtained in non HCV-infected
      patients. Moreover, these scores can identify candidates with a high risk of
      mortality in whom the use of a new organ would be unreasonable. Prevention of
      severe hepatitis C recurrence could be the first step to avoid RT. Thus,
      antiviral treatment on the waiting list (if possible) and early identification
      and treatment of patients with severe hepatitis C recurrence may be a good
      strategy to avoid RT. In addition, active management of factors which can
      accelerate fibrosis progression (donor age, post-transplant diabetes, high dose
      of corticosteroids) might reduce the incidence of severe forms of hepatitis C
      recurrence.

PMID- 20800308
TI  - Fibroblast growth factor 21 as a biomarker for NAFLD: integrating pathobiology
      into clinical practice.

PMID- 20800309
TI  - Malignant but not naive hepatocytes of human and rodent origin are killed by TNF
      after metabolic depletion of ATP by fructose.
AB  - BACKGROUND & AIMS: TNF was the first cytokine employed for cancer therapy, but
      its use was limited due to its insufficient selectivity towards malignant cells.
      Fructose induces transient hepatic ATP depletion in humans and rodents due to the
      liver-specific fructose metabolism via fructokinase, while other cells e.g.
      Muscle cells metabolize fructose via hexokinase. Under ATP depleted conditions
      hepatocytes are protected against TNF-induced apoptosis. Our aim was to identify
      metabolic differences between normal and malignant liver cells that can be
      exploited for selective immunotherapy. METHODS: We analyzed the expression and
      activities of enzymes involved in fructose metabolism in primary hepatocytes and
      hepatoma cell lines. Furthermore, we studied the influence of hexokinase II
      (HKII) on fructose-mediated ATP depletion and cytoprotection in murine
      hepatocytes. RESULTS: Primary mouse, rat and human hepatocytes depleted of ATP by
      fructose were fully protected against TNF-induced cytotoxicity. By contrast,
      hepatic tumor cell lines showed increased HKII expression, lack of fructose
      mediated ATP depletion and, therefore, remained susceptible to TNF/ActD-induced
      apoptosis. Inhibition of hexokinases restored fructose-induced ATP depletion in
      hepg2 cells. Finally, hypoxia-inducible factor1 (HIF1)-mediated up-regulation of
      HKII prevented fructose-induced ATP depletion and overexpression of HKII
      inhibited fructose-mediated cytoprotection against TNF-induced apoptosis in
      primary murine hepatocytes. CONCLUSION: Increased expression of HKII in malignant
      cells of hepatic origin shifts the fructose metabolism from liver- to muscle
      type, thereby preventing ATP depletion and subsequent cytoprotection of the
      target cells. Therefore, healthy liver cells are transiently protected from TNF
      mediated cell death by fructose-induced ATP depletion, while malignant cells can
      be selectively eliminated through TNF-induced apoptosis.

PMID- 20800310
TI  - Flexible employment and nurses' intention to leave the profession: The role of
      support at work.
AB  - OBJECTIVES: The objectives of this paper are to examine (1) the association
      between flexible employment and nurses' intention to leave the profession, and
      (2) whether or not support at work mediates the association between flexible
      employment and nurses' intention to leave the profession. Flexible employment is
      analyzed objectively using non-permanent contract, part-time employment status,
      casual employment status, involuntary hours and on-call work, and subjectively
      using job insecurity. Support at work refers to organizational, supervisor and
      peer support. METHODS: Data come from our survey of 1396 nurses employed in three
      teaching hospitals in Southern Ontario. Descriptive statistics are provided.
      Bivariate correlations, hierarchical regression analysis and mediation tests are
      conducted. RESULTS: Compared to those in full-time employment, nurses in part
      time employment do not intend to leave the profession. None of the other
      objective flexible employment factors are associated with intention to leave the
      profession. Perceived job insecurity is associated with intention to leave the
      profession. Low support at work contributes to intention to leave the profession
      and mediates the association between job insecurity and intention to leave the
      profession. CONCLUSIONS: The study provides evidence to health sector managers
      and policy makers that part-time employment, perceived job security and support
      at work are important factors to consider in efforts to retain nurses in the
      profession.

PMID- 20800311
TI  - An analysis of hospital capital planning and financing in three European
      countries: Using the principal-agent approach to identify the potential for
      economic problems.
AB  - OBJECTIVE: To explore differences in national approaches to hospital capital
      planning and financing in three European countries and to understand the roles
      and positions of the actors involved. METHODS: Case studies of major new hospital
      developments were undertaken in each of the study countries (France, Sweden and
      England), based on a review of documents related to each development and the
      national framework within which they took place, as well as interviews with key
      informants. The principal-agent model was used, focusing on identification of
      differing utilities and information asymmetries. RESULTS: There are substantial
      differences between countries, for example in relation to the role of the
      hospital in its own redevelopment, the organisational distance between actors,
      the institutional level at which decision rights for major investments are
      exercised, and how principals control the agents. These differences have
      implications for the processes involved and the nature of economic and health
      care problems that can arise. CONCLUSIONS: There is evidence of, and opportunity
      for economic problems in all systems but these seems to be greater in France and
      England where the hospital leads the process, where there is limited involvement
      by the regional bodies, and informational differences appear greater. We conclude
      that hospital planning processes should be informed by an explicit understanding
      of the powerful groups involved and their divergent preferences and utilities.

PMID- 20800312
TI  - Time for a paradigm change? Tracing the institutionalisation of health impact
      assessment in the Republic of Ireland across health and environmental sectors.
AB  - This paper presents a critical analysis of health impact assessment (HIA) in the
      Republic of Ireland (ROI) in the context of institutional policy and practice. It
      begins with a brief background to the origins and aims of HIA. Core developments
      in health and environmental sectors pertaining to HIA in the ROI are then
      considered. A series of significant developments have taken place in these
      sectors over the past decade that are positively associated with the promotion of
      HIA in the ROI. However, it is argued that in spite of various institutional
      facilitators, the practice of implementing HIAs in the ROI is significantly
      underdeveloped, and it continues to lag behind several of its European Union
      counterparts. It is contended that a paradigm change is required in order to
      address the current policy-action gap. An organisation theory framework is used
      to assess the implementation problem and a number of suggestions are highlighted
      as potential facilitators of this process.

PMID- 20800313
TI  - Crosstalk between genetic and epigenetic information through cytosine
      deamination.
AB  - Decades of work have elucidated the existence of two forms of heritable
      information, namely genetic and epigenetic, which are collectively referred to as
      the 'dual inheritance'. The underlying mechanisms behind these two modes of
      inheritance have so far remained distinct. Cytosine deaminases, such as
      activation-induced cytidine deaminase (AID) and other members of the APOBEC
      family, have been implicated both in genetic variation of somatic cells and in
      epigenetic remodeling of germ and pluripotent cells. We hereby synthesize these
      seemingly dissociated functions into one coherent model, and further suggest that
      cytosine deaminases, particularly AID, might have a broader influence by
      modulating epigenetic information in somatic or cancer cells, as well as by
      triggering genetic variation in germ and pluripotent cells through mutation
      followed by natural selection. We therefore propose that the AID/APOBEC family of
      deaminases are likely to have acted as drivers throughout vertebrate evolution.

PMID- 20800314
TI  - Independent cohort cross-validation of the real-time DISTq estimation of insulin
      sensitivity.
AB  - Insulin sensitivity (SI) is useful in the diagnosis, screening and treatment of
      diabetes. However, most current tests cannot provide an accurate, immediate or
      real-time estimate. The DISTq method does not require insulin or C-peptide assays
      like most SI tests, thus enabling real-time, low-cost SI estimation. The method
      uses a posteriori parameter estimations in the absence of insulin or C-peptide
      assays to simulate accurate, patient-specific, insulin concentrations that enable
      SI identification. Mathematical functions for the a posteriori parameter
      estimates were generated using data from 46 fully sampled DIST tests (glucose,
      insulin and C-peptide). SI values found using the DISTq from the 46 test pilot
      cohort and a second independent 218 test cohort correlated R=0.890 and R=0.825,
      respectively, to the fully sampled (including insulin and C-peptide assays) DIST
      SI metrics. When the a posteriori insulin estimation functions were derived using
      the second cohort, correlations for the pilot and second cohorts reduced to 0.765
      and 0.818, respectively. These results show accurate SI estimation is possible in
      the absence of insulin or C-peptide assays using the proposed method. Such
      estimates may only need to be generated once and then used repeatedly in the
      future for isolated cohorts. The reduced correlation using the second cohort was
      due to this cohort's bias towards low SI insulin resistant subjects, limiting the
      data set's ability to generalise over a wider range. All the correlations remain
      high enough for the DISTq to be a useful test for a number of clinical
      applications. The unique real-time results can be generated within minutes of
      testing as no insulin and C-peptide assays are required and may enable new
      clinical applications.

PMID- 20800315
TI  - Biodiversity baselines, thresholds and resilience: testing predictions and
      assumptions using palaeoecological data.
AB  - Fossil records are replete with examples of long-term biotic responses to past
      climate change. One particularly useful set of records are those preserved in
      lake and marine sediments, recording both climate changes and corresponding
      biotic responses. Recently there has been increasing focus on the need for
      conservation of ecological and evolutionary processes in the face of climate
      change. We review key areas where palaeoecological archives contribute to this
      conservation goal, namely: (i) determination of rates and nature of biodiversity
      response to climate change; (ii) climate processes responsible for ecological
      thresholds; (iii) identification of ecological resilience to climate change; and
      (iv) management of novel ecosystems. We stress the importance of long-term
      palaeoecological data in fully understanding contemporary and future biotic
      responses.

PMID- 20800316
TI  - Rising to the challenge of sustaining coral reef resilience.
AB  - Phase-shifts from one persistent assemblage of species to another have become
      increasingly commonplace on coral reefs and in many other ecosystems due to
      escalating human impacts. Coral reef science, monitoring and global assessments
      have focused mainly on producing detailed descriptions of reef decline, and
      continue to pay insufficient attention to the underlying processes causing
      degradation. A more productive way forward is to harness new theoretical insights
      and empirical information on why some reefs degrade and others do not. Learning
      how to avoid undesirable phase-shifts, and how to reverse them when they occur,
      requires an urgent reform of scientific approaches, policies, governance
      structures and coral reef management.

PMID- 20800317
TI  - NMR measurement of hydrodynamic dispersion in porous media subject to biofilm
      mediated precipitation reactions.
AB  - Noninvasive measurements of hydrodynamic dispersion by nuclear magnetic resonance
      (NMR) are made in a model porous system before and after a biologically mediated
      precipitation reaction. Traditional magnetic resonance imaging (MRI) was unable
      to detect the small scale changes in pore structure visualized during light
      microscopy analysis after destructive sampling of the porous medium. However,
      pulse gradient spin echo nuclear magnetic resonance (PGSE NMR) measurements
      clearly indicated a change in hydrodynamics including increased pore scale
      mixing. These changes were detected through time-dependent measurement of the
      propagator by PGSE NMR. The dynamics indicate an increased pore scale mixing
      which alters the preasymptotic approach to asymptotic Gaussian dynamics governed
      by the advection diffusion equation. The methods described here can be used in
      the future to directly measure the transport of solutes in biomineral-affected
      porous media and contribute towards reactive transport models, which take into
      account the influence of pore scale changes in hydrodynamics.

PMID- 20800318
TI  - The molecular genetics underlying basal cell carcinoma pathogenesis and links to
      targeted therapeutics.
AB  - Mutations in the sonic hedgehog signaling pathway play a key role in the
      development of basal cell carcinomas. Specifically, mutations in the PTCH1 (also
      known as PTCH or PTC1) and SMO genes cause tumor formation through constitutive
      activation of the pathway. Misregulation of the pathway has also been implicated
      in the nevoid basal cell carcinoma syndrome and other tumors. Understanding the
      function of the sonic hedgehog pathway has led to novel strategies for treatment.
      In this review we highlight the role of the pathway in the pathogenesis of basal
      cell carcinoma and review potential targeted therapies.

PMID- 20800319
TI  - Cutaneous lupus erythematosus: update of therapeutic options part II.
AB  - In the first part of the review, topical agents and first-line systemic treatment
      options for cutaneous lupus erythematosus were discussed whereas in the second
      part, recent information on efficacy, dosage, and side effects for further
      systemic treatment options are described in detail. In contrast to other
      immunosuppressive agents, such as azathioprine, cyclophosphamide, and
      cyclosporine, methotrexate has recently received more attention in the treatment
      of the disease. Further second-line treatment includes retinoids, dapsone, and
      mycophenolate mofetil. Because of severe side effects or high costs, other
      agents, such as thalidomide or high-dose intravenous immunoglobulins, are
      reserved for severe recalcitrant CLE. Biologics, ie, rituximab, have been used to
      treat systemic lupus erythematosus; however, in CLE, most biologics have only
      been applied in single cases. In addition to successful treatment, induction of
      CLE subtypes by biologics has been reported. In conclusion, many treatment
      options exist for CLE, but not many are supported by evidence from randomized
      controlled trials.

PMID- 20800320
TI  - Prospective study of wound infections in Mohs micrographic surgery using clean
      surgical technique in the absence of prophylactic antibiotics.
AB  - BACKGROUND: Mohs micrographic surgery (MMS) has a low rate of surgical site
      infection (SSI) without the use of prophylactic antibiotics. In the studies to
      date, there has been variation in the steps taken by each surgeon to prevent SSIs
      but in all cases sterile technique was used during wound reconstruction.
      OBJECTIVE: We sought to evaluate the rate of SSIs among patients undergoing MMS
      with the use of clean surgical technique for all steps of MMS including wound
      reconstruction in the absence of prophylactic antibiotics. METHODS: We
      prospectively evaluated 1000 patients undergoing MMS using clean surgical
      technique for SSIs. Clean surgical technique includes the use of clean surgical
      gloves and towels and a single pack of sterile instruments for all steps
      including wound reconstruction. RESULTS: There were 11 SSIs among 1000 patients
      with 1204 tumors, with an overall rate of infection of 0.91% (95% confidence
      interval 0.38%-1.45%). Three of the 11 infections were complications of
      hematomas. Four of the 11 infections occurred in flap closures, which had the
      highest rate of SSIs of 2.67% (4/150). LIMITATIONS: The study was a prospective,
      single-institution uncontrolled study. CONCLUSION: To our knowledge, this is the
      first study to examine the rate of SSIs with the use of clean surgical technique,
      in the absence of antibiotic prophylaxis, for all steps of MMS including wound
      reconstruction. Our rate of SSIs of 0.91% is exceedingly low, underscoring the
      overall safety of MMS and its performance in the outpatient setting without the
      use of antibiotic prophylaxis or sterile technique.

PMID- 20800321
TI  - Chemometric modeling of free radical scavenging activity of flavone derivatives.
AB  - The present work deals with the chemometric modeling of antioxidant molecules
      belonging to the class of flavone derivatives employing the quantitative
      structure-activity relationship (QSAR) technique. A QSAR model was initially
      built based on the Fujita-Ban method with the training set molecules. Due to the
      inability of the Fujita-Ban type model to predict satisfactorily the activity of
      the test set molecules, further QSAR models were built using different
      chemometric tools (genetic function approximation, genetic partial least squares)
      with additional descriptors viz., topological, structural, spatial and quantum
      chemical ones. The statistically significant models thus developed suggest that
      hydroxy and methoxy substituents at certain specified positions of the A and B
      rings of the flavone moiety chiefly influence the antioxidant activity of these
      molecules.

PMID- 20800322
TI  - Synthesis, biological assay in vitro and molecular docking studies of new
      imidazopyrazinone derivatives as potential dipeptidyl peptidase IV inhibitors.
AB  - A series of novel imidazopyrazinone derivatives were synthesized and evaluated
      with regard to their ability to inhibit dipeptidyl peptidase IV (DPP-IV) in
      vitro. Of these compounds (2R)-4-oxo-4-[2-(3-carbamoylbenzyl)-hexahydro-3
      oxoimidazo [1,5-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine
      fumaric acid (17h, IC(50)=78 nM) was shown to effectively inhibit the activity of
      the dipeptidyl peptidase IV enzyme. Molecular docking studies were also performed
      to illustrate the binding mode of compounds 15c and 17h. Favorable interactions
      were identified from the binding of inhibitor 15c with DPP-IV. By analogy to the
      binding mode of compound 15c, it seems that the introduction of a substituted
      benzyl moiety onto the imidazopyrazinone could remarkably improve the inhibitory
      activity of compound 17h.

PMID- 20800323
TI  - [Diagnostic strategy and comparison of clinical scores for pulmonary embolism].
AB  - The diagnostic approach to pulmonary embolism can be divided in several
      consecutive steps. First of all, the clinician must identify the patients with
      potential pulmonary embolism based on clinical presentation and the presence or
      absence of personal risk factors. Further investigations can then be guided by
      the use of a clinical probability score. The revised Geneva score and the Wells
      score are the most validated tools. They are reliable in stratifying patients
      into low, intermediate, and high-risk categories. When clinical probability is
      low or intermediate, the dosage of d-dimers is helpful. A negative result
      excludes pulmonary embolism with a very high negative predictive value, close to
      100%. When positive, a multidetector thoracic CT will confirm or exclude the
      diagnosis. The utility of a lower-limb venous ultrasound is very low, and its use
      is therefore no longer recommended.

PMID- 20800324
TI  - C. Wright Mills on intellectual craftsmanship.

PMID- 20800325
TI  - Differences in fat content and fatty acid proportions among colostrum,
      transitional, and mature milk from women delivering very preterm, preterm, and
      term infants.
AB  - BACKGROUND & AIMS: Human milk composition changes according to gestational age
      and stage of lactation, but infants fed banked human milk often receive pooled
      milk. We studied the changes in fat content and fatty acid proportions throughout
      lactation in very preterm, preterm, and full term milk, and the differences among
      gestational age groups. METHODS: Samples from women delivering before 30 (n =
      10), between 30 and 37 (n = 10), and between 38 and 42 (n = 23) weeks of
      gestation were analyzed. RESULTS: Fat content was higher in very preterm than in
      preterm and full term samples (p < 0.05). Medium-chain saturated fatty acids,
      alpha-linolenic acid, and rumenic acid proportions increased (p < 0.05) during
      lactation, while those of most long-chain saturated fatty acids and most long
      chain polyunsaturated fatty acids from the n-3 and n-6 families decreased (p <
      0.05). In colostrum and transitional milk, medium-chain saturated fatty acid
      proportions were highest in the very preterm group, and decreased with
      gestational age (p < 0.05). CONCLUSIONS: The differences in fat and fatty acids
      of human milk obtained at different gestational ages and stages of lactation may
      impact preterm infants' health. Therefore they could be taken into account when
      feeding newborns banked human milk and when designing infant formulas or human
      milk fortifiers.

PMID- 20800326
TI  - Does cancellous bone compaction due to insertion of a blade implant influence the
      cut-out resistance? A biomechanical study.
AB  - BACKGROUND: For the treatment of hip fractures helically shaped implants, like
      the Dynamic Hip Screw (DHS) Blade, are often used. One consequence of blade
      implantation, the compaction of cancellous bone, is still believed to increase
      cut-out resistance. This in vitro study investigates implant anchorage of Dynamic
      Hip Screw Blades in femoral heads due to insertion with or without predrilling
      under cyclic physiological loading conditions. METHODS: Six pairs of fresh frozen
      (-20 degrees C) human cadaveric proximal femora were instrumented with DHS
      Blades. Bone pairs were randomly assigned to two study groups: 1) predrilled; 2)
      non-predrilled. Prior instrumentation, bone mineral density was determined in the
      center of the femoral head by Xtreme-CT measurement. After instrumentation
      biomechanical testing was performed under cyclic loading. The bone-implant
      interface was monitored by means of fluoroscopic imaging throughout the
      experiment. Paired t-tests were performed to identify differences regarding bone
      mineral density, stiffness and cycles to failure. FINDINGS: No significant
      differences were found between study groups with regard to axial stiffness
      (P=0.626) and number of cycles to failure (P=0.961). INTERPRETATION: This in
      vitro study did not show differences in biomechanical stability of proximal
      femora instrumented with a helical blade implant with or without predrilling.
      Clinically, the findings suggest that predrilling may be performed to ease the
      surgical procedure without compromising the implant anchorage.

PMID- 20800328
TI  - Survival from out-of-hospital cardiac arrest in New Zealand following the 2005
      resuscitation guideline changes.
AB  - AIMS: The effect of cardiopulmonary resuscitation guideline changes on out-of
      hospital survival rates and defibrillation efficacy was investigated. The
      guideline changes were those recommended by the International Liaison Committee
      on Resuscitation in 2005. METHODS: A retrospective comparative study was
      undertaken of out-of-hospital cardiac arrests in the Wellington region. The
      effect of guideline changes between the periods of 1st July 2005-30th June 2006
      and 1st June 2007-31st May 2008 was examined. Data was collected from Wellington
      Free Ambulance and hospital records in accordance with the Utstein template. The
      primary outcome measure was survival to hospital discharge. Additional end points
      included individual shock success, return of spontaneous circulation (ROSC) and
      survival to hospital admission. RESULTS: There was no significant increase in
      survival to hospital discharge with 11% (18/162) pre-change and 12% (20/170) post
      change (p=0.5). First-shock efficacy decreased from 68% (65/96) to 62% (57/92)
      (p=0.75). Second shock efficacy decreased from 47% (14/30) to 27% (9/33)
      (p=0.12). The proportion of patients with ROSC increased from 34% (55/162) to 42%
      (72/170) (p=0.07, Chi squared). The proportion surviving to hospital increased
      significantly from 22% (36/162) to 36% (61/170) (p=0.006). Withdrawal of atropine
      in 2005 had no adverse effect on the outcome. CONCLUSION: This study suggests
      that in the Wellington Region of New Zealand, the new guidelines have improved
      survival to hospital but not to discharge. Whilst the guideline changes have
      resulted in a trend towards decreased shock success rates, ROSC and survival to
      hospital admission have both increased.

PMID- 20800327
TI  - Cognitive impairment and 7-year mortality in dialysis patients.
AB  - BACKGROUND: Although dementia has predicted mortality in large dialysis cohorts,
      little is known about the relationship between less pronounced cognitive deficits
      and mortality in patients with end-stage renal disease. This study assessed
      whether cognitive impairment without dementia was an independent predictor of 7
      year survival in dialysis patients after controlling for other risk factors.
      STUDY DESIGN: Prospective single-cohort study. SETTING & PARTICIPANTS: 145
      prevalent dialysis patients from 2 units in London, UK, were followed up for 64.3
      +/- 27.4 months and censored at the time of change to a different treatment.
      PREDICTORS: Cognitive impairment, defined as performance 1 standard deviation
      less than normative values on 2 or more cognitive tests within a neurocognitive
      battery assessing attention/concentration, memory, and psychomotor function
      domains. Depression, quality-of-life, and clinical measures also were obtained.
      OUTCOMES & MEASUREMENTS: All-cause mortality was the primary outcome. Cox
      proportional hazard models were used to assess the contribution of demographics
      and clinical and psychological measures and cognitive impairment to mortality.
      RESULTS: 98 (67.6%) patients were cognitively impaired at baseline. At follow-up,
      56 (38.6%) patients had died, 29 of cardiac causes. Unadjusted Kaplan-Meier
      analysis showed higher mortality in cognitively impaired patients, in whom 7-year
      survival was 49% versus 83.2% in those with no cognitive impairment (P < 0.001).
      Mortality risk associated with cognitive impairment remained significant in
      adjusted analysis controlling for sociodemographic, clinical, and psychological
      factors (adjusted HR, 2.53; 95% CI, 1.03-6.22; P = 0.04). LIMITATIONS: Small
      sample size and number of events. CONCLUSIONS: Cognitive impairment is an
      independent predictor of mortality in dialysis patients. Although the
      implications of early recognition and treatment of cognitive impairment for
      clinical outcomes are unclear, these results suggest that patient management
      protocols should attempt to ensure prevention of cognitive decline in addition to
      managing coexisting medical conditions.

PMID- 20800329
TI  - Cardiopulmonary resuscitation (CPR) survival rates and Internet search for CPR:
      is there a relation?

PMID- 20800330
TI  - Is there a role for remote ischaemic postconditioning in cardiopulmonary
      resuscitation?
AB  - Cardiac arrest causes whole body ischaemic injury and cellular death. Successful
      cardiopulmonary resuscitation (CPR) can subsequently lead to a global reperfusion
      phenomenon with a paradoxically increased rate of cellular death. Interventions
      that decrease the ischaemia-reperfusion injury may be useful in the treatment of
      these patients. Remote ischaemic postconditioning with transient limb ischaemia
      is feasible in cardiac arrest patients. This article discusses the concept of
      ischaemic pre- and postconditioning and its potential use in patients during CPR
      and after return of a spontaneous circulation.

PMID- 20800331
TI  - External cardiac massage improved cerebral tissue oxygenation shown by near
      infrared spectroscopy during transcatheter aortic valve implantation.

PMID- 20800332
TI  - Use of simulation-based medical education to improve patient care quality.

PMID- 20800333
TI  - Does change in thoracic impedance measured via defibrillator electrode pads
      accurately detect ventilation breaths in children?
AB  - INTRODUCTION: Resuscitation guidelines recommend rescue ventilations consist of
      tidal volumes 7-10 ml/kg. Changes in thoracic impedance (DeltaTI) measured using
      defibrillator electrode pads to detect and guide rescue ventilations have not
      been studied in children. AIM: We hypothesized that DeltaTI measured via standard
      anterior-apical (AA) position can accurately detect ventilations with volume > 7
      ml/kg in children. We also compared standard AA position with alternative
      anterior-posterior (AP) position. METHODS: IRB-approved, prospective,
      observational study of sedated, subjects (6 months to 17 years) on conventional
      mechanical ventilation. Thoracic impedance (TI) was obtained via Philips MRx
      defibrillator with standard electrode pads for 5 min each in AA and AP positions.
      Ventilations were simultaneously measured by pneumotachometer (Novametrix
      CO(2)SMO Plus). RESULTS: Twenty-eight subjects (median 4 years, IQR 1.7-9 years;
      median 16.3 kg, IQR 10.5-39 kg) were enrolled. Data were available for 21
      episodes in AA position and 22 episodes in AP position, with paired AA and AP
      data available for 18. For ventilations with volume < 7 ml/kg, the defibrillator
      algorithm detected 80.0% for both AA and AP (p=0.99). For ventilations >= 7
      ml/kg, detection was 95.1% for AA and 95.7% for AP (p=0.38). CONCLUSIONS: Changes
      in thoracic impedance obtained via defibrillator pads can accurately detect
      ventilations above 7 ml/kg in stable, mechanically ventilated children,
      corresponding to rescue ventilations recommended during CPR. Both AA and AP pad
      positions were less sensitive to detect smaller volumes (< 7 ml/kg) than higher
      volumes (>= 7 ml/kg), suggesting that shallow ventilations during CPR might be
      missed. There were no differences in impedance measurements between standard AA
      pad position and commonly used alternative AP pad position.

PMID- 20800334
TI  - Socioeconomic disparities in the knowledge of basic life support techniques.
AB  - OBJECTIVES: Substantial disparities exist in health measures between different
      socioeconomic groups, including mortality. We hypothesized that a difference in
      knowledge of life-saving basic life support (BLS) techniques between groups may
      also contribute. METHODS: A 34-question survey was administered to a convenience
      sample of patients 18 and older presenting to an urban ED in Boston. Patients who
      were intoxicated, prisoners, critically or mentally ill, had an insurmountable
      language barrier or victims of abuse were excluded. Trained research assistants
      collected the data. An inactivated automated external defibrillator (AED) device
      was utilized to test identification of the device and its correct usage. RESULTS:
      440 patients were considered for inclusion. 163 patients met exclusion criteria,
      leaving 277 eligible patients. 59 patients refused, and 218 patients (78.7%)
      completed the survey instrument. Overall, 144 (66.7% (95% CI 60.1-72.6%)) felt
      confident recognizing the signs of a heart attack. 93 (42.9% (95% CI 36.5-49.5%))
      recognized that heart attack symptoms were different in men and women. 112 (51.3%
      (95% CI 44.8-57.9%)) were trained to do CPR. Patients were more likely to be
      trained in CPR if English is their first language (OR 2.25 (1.18-4.28) p=0.012)
      or if they earned >$40,000 per year (OR 2.15 (1.17-3.95) p=0.013). Recognition of
      the AED was more common in those who completed college (OR 2.70 (1.52-4.78)
      p=0.0005), were white (OR 1.78 (1.03-3.08) p=0.036), had English as the 1st
      language (OR 3.33 (1.63-6.81) p=0.0005), earned >$40,000 per year (OR 3.21 (1.70
      6.06) p=0.0002) or had private insurance (OR 2.32 (1.33-4.04) p=0.003).
      Demonstration of correct usage of the AED was more common in patients who
      completed college (OR 1.91 (1.09-3.32) p=0.022) and had private insurance (OR
      2.19 (1.26-3.82) p=0.005). No differences were detected between the genders, age
      > or < than 50, or patients who have a PCP. CONCLUSIONS: Multiple socioeconomic
      disparities exist in the knowledge of BLS techniques. This study describes these
      disparities, and presents an opportunity to target education and potentially
      reduce mortality for these specific groups.

PMID- 20800336
TI  - Fetal myocardial morphological and functional changes associated with well
      controlled gestational diabetes.
AB  - OBJECTIVE: To make a global evaluation of the fetal myocardial changes in a well
      controlled gestational diabetic population. STUDY DESIGN: Twenty-four pregnant
      well-controlled diabetic patients were selected. Sixteen normal pregnancies were
      randomly collected as a control group. Measurements of morphological and
      functional myocardial parameters were performed. Data from the left ventricular
      outflow tract and peripheral Doppler data were obtained. RESULT: The thickness of
      the interventricular septum was increased in diabetic pregnancies (p < 0.001).
      Tricuspid E/A index was the only functional parameter showing a significant
      variation, with lower values in diabetic pregnancies. Doppler parameters from the
      left ventricular outflow tract and peripheral Doppler waveforms were similar
      between groups. CONCLUSION: A tendency towards interventricular septum
      hypertrophy was observed even in well-controlled diabetic pregnancies. Mild
      hypertrophic cardiac changes were not associated with abnormal cardiac function
      or signs of left ventricular outflow obstruction, although minor changes in right
      ventricular diastolic function were recorded.

PMID- 20800337
TI  - Benign metastasizing leiomyoma of external iliac vessels: an unusual case report.

PMID- 20800338
TI  - Retroperitoneal and transperitoneal robot-assisted pyeloplasty in adults:
      techniques and results.
AB  - BACKGROUND: The surgical management of ureteropelvic junction obstruction (UPJO)
      has dramatically evolved over the past 20 yr due to the development of new
      technology. OBJECTIVE: Our aim was to report the feasibility and efficacy of
      robot-assisted pyeloplasty (RAP) performed by either the retroperitoneal or the
      transperitoneal approach. DESIGN, SETTING, AND PARTICIPANTS: A stage 2
      investigative study was conducted including development (stage 2a) and
      exploration (stage 2b) of transperitoneal and retroperitoneal RAP performed in 55
      patients at an urban tertiary university department of urology. SURGICAL
      PROCEDURE: Retroperitoneal RAP was performed with the patient in full flank
      position using a 12-mm Hasson-style optical port at the tip of the 12th rib, plus
      two operative 8-mm robotic trocars and an assistant 5-mm port. The stenotic
      ureteropelvic junction was excised, the ureter was spatulated, and a dismembered
      pyeloplasty was performed in all cases. Transperitoneal RAP was performed with
      the patients in the 60 degrees  flank position. The optical port is in the
      umbilical area, plus two 8-mm operative robotic ports and one 5-mm assistant
      port. The pyeloplasty technique is similar to the retroperitoneoscopic approach.
      In both groups, the stent can be positioned in an anterograde or retrograde
      fashion. MEASUREMENTS: Success consisted of no evidence of obstruction on
      computed tomography urography or mercaptoacetyltriglycine-3 diuretic renal scan,
      no postoperative symptoms, and no further treatment. RESULTS AND LIMITATIONS:
      Thirty-six patients underwent retroperitoneoscopic RAP and 19 transperitoneal RAP
      for UPJO. All the procedures were completed with robotic assistance. The overall
      objective success (measured by diuretic renal scan and/or imaging techniques) was
      96% with two cases of recurrence (both in the retroperitoneal group). The main
      limitation was the short follow-up, although all patients reached at least a 6-mo
      follow-up. CONCLUSIONS: RAP performed either retroperitoneally or
      transperitoneally was revealed as a feasible and reproducible surgical option for
      the treatment of UPJO, offering a subjective optimal plasty reconfiguration at
      short follow-up.

PMID- 20800339
TI  - Prognostic factors for occult inguinal lymph node involvement in penile carcinoma
      and assessment of the high-risk EAU subgroup: a two-institution analysis of 342
      clinically node-negative patients.
AB  - BACKGROUND: The European Association of Urology (EAU) guidelines advise an
      elective bilateral lymphadenectomy in clinically node-negative (cN0) patients
      with high-risk penile carcinoma (>=pT2, G3, or lymphovascular invasion [LVI]).
      OBJECTIVE: Our aim was to assess prognostic factors for occult metastasis and to
      determine whether current EAU guidelines accurately stratify patients at high
      risk. DESIGN, SETTING, AND PARTICIPANTS: Data of 342 cN0 patients with
      histologically proven invasive penile squamous cell carcinoma who had undergone
      the current dynamic sentinel node biopsy (DSNB) protocol were analysed. A
      complete ipsilateral inguinal lymphadenectomy was only done if the sentinel node
      was tumour positive. MEASUREMENTS: The presence of occult metastasis was
      established by preoperative ultrasound and tumour-positive fine-needle aspiration
      cytology, tumour-positive sentinel nodes, and groin metastases during follow-up
      after a negative DSNB procedure. Median follow-up was 31 mo. RESULTS AND
      LIMITATIONS: Sixty-eight of 342 patients (20%) and 87 of 684 groins (13%) had
      occult nodal involvement including 6 patients (2%) with a groin metastasis after
      negative DSNB. Corpus spongiosum invasion, corpus cavernosum invasion, histologic
      grade, and LVI were each significant prognosticators for occult metastasis on
      univariate analysis. On multivariate analysis, grade (odds ratio [OR]: 3.3 for
      intermediate and 4.9 for poor, respectively) and LVI (OR: 2.2) remained
      predictive factors. In total, 245 patients (72%) were classified high risk
      according to EAU guidelines. Among them, the incidence of occult metastasis was
      23% (57 of 245). A potential limitation of this study is the lack of external
      review. CONCLUSIONS: Histologic grade and LVI are independent prognostic factors
      for occult metastasis in penile carcinoma. Although both predictors are
      incorporated into the current EAU guidelines, the stratification of patients
      needing a lymph node dissection is inaccurate. Approximately 77% of high-risk
      patients (188 of 245) would have had a negative bilateral inguinal
      lymphadenectomy. For the time being, DSNB is considered a more suitable staging
      method than EAU risk stratification for an accurate determination of patients who
      require lymph node dissection.

PMID- 20800340
TI  - A prospective, randomised trial comparing plasmakinetic enucleation to standard
      transurethral resection of the prostate for symptomatic benign prostatic
      hyperplasia: three-year follow-up results.
AB  - BACKGROUND: Plasmakinetic enucleation of the prostate (PKEP) has recently been
      proved a safe and technically feasible procedure for benign prostatic hyperplasia
      (BPH). However, its long-term safety, efficacy, and durability in comparison with
      the gold-standard transurethral resection of the prostate (TURP) have not yet
      been reported. OBJECTIVE: To report the 3-yr follow-up results of a prospective,
      randomised clinical trial comparing PKEP with standard TURP for symptomatic BPH.
      DESIGN, SETTING, AND PARTICIPANTS: A total of 204 patients with bladder outflow
      obstruction (BOO) secondary to BPH were prospectively randomised 1:1 into either
      the PKEP group or the TURP group. INTERVENTION: The patients in each group
      underwent the procedure accordingly. MEASUREMENTS: All patients were assessed
      perioperatively and followed at 1, 3, 6, 12, 18, 24, and 36 mo postoperatively.
      The preoperative and postoperative parameters included International Prostate
      Symptom Score (IPSS), quality of life (QoL) scores, the International Index of
      Erectile Function (IIEF) questionnaire, maximum urinary flow rates (Q(max)),
      transrectal ultrasound (TRUS)-assessed prostate volume, postvoid residual urine
      (PVRU) volume, and serum prostate-specific antigen (PSA) level. Patient baseline
      characteristics, perioperative data, and postoperative outcomes were compared.
      All complications were recorded. RESULTS AND LIMITATIONS: PKEP was significantly
      superior to TURP in terms of the drop in haemoglobin (0.74+/-0.33 g/dl vs 1.88+/
      1.06 g/dl; p<0.001), intraoperative irrigation volume (11.7+/-4.5 l vs 15.4+/-6.2
      l; p<0.001), postoperative irrigation volume and time (18.5+/-7.6 l vs. 30.0+/
      11.4 l and 16.6+/-5.2 h vs 25.3+/-8.5 h; all p<0.001), recovery room stay (67.3+/
      11.1 min vs 82.0+/-16.4 min; p<0.001), catheterisation time (51.7+/-26.3 h vs
      80.5+/-31.6 h; p<0.001), hospital stay (98.4+/-20.4 h vs 134.2+/-31.5 h;
      p<0.001), and resected tissue (56.4+/-12.8 g vs 43.8+/-15.5 g; p<0.001). There
      were no statistical differences in operation time and sexual function between the
      two groups. At 36 mo postoperatively, the PKEP group had a maintained and
      statistically significant improvement in IPSS (2.4+/-2.2 vs 4.3+/-2.9; p<0.001),
      QoL (0.6+/-0.5 vs 1.6+/-1.4; p<0.001), Q(max) (28.8+/-10.1 ml/s vs 25.1+/-8.0
      ml/s; p=0.017), and TRUS volume (21.0+/-7.3 ml vs 26.4+/-6.8 ml; p<0.001), with
      urodynamically proven deobstruction (Schafer grade 0.2+/-0.02 vs 0.8+/-0.1;
      p<0.001). More extensive clinical trials are required to validate these results.
      CONCLUSIONS: PKEP is a safe and highly effective technique for relieving BOO. At
      3-yr follow-up, the clinical efficacy of PKEP is durable and compares favourably
      with TURP.

PMID- 20800341
TI  - Complications in 2200 consecutive laparoscopic radical prostatectomies:
      standardised evaluation and analysis of learning curves.
AB  - BACKGROUND: Laparoscopic radical prostatectomy (LRP) represents an established
      treatment modality for localised prostate cancer. OBJECTIVE: To report
      standardised complication rates for LRP, evaluate the development of complication
      rates over time, and show changes within the learning curves of laparoscopic
      surgeons. DESIGN, SETTING, AND PARTICIPANTS: We conducted a standardised analysis
      of 2200 consecutive patients who underwent LRP between 1999 and 2008 at a single
      institution. INTERVENTION: LRP was performed using a transperitoneal (n=871) or
      extraperitoneal (n=1329) retrograde Heilbronn technique. Five surgeons operated
      on 96% of the patients. MEASUREMENTS: Complications were classified according to
      the modified Clavien system. Total complication rates and changes over time were
      analysed. Three generations of surgeons were defined for evaluation of learning
      curves. RESULTS AND LIMITATIONS: Minor complications occurred in 21.7% of
      patients (Clavien 1: 6.8%; Clavien 2: 14.9%); anaemia requiring transfusion
      (10.4%) dominated. Early reinterventions were necessary in 6.7% of patients
      (Clavien 3a: 3.6%; Clavien 3b: 1.5%; Clavien 4a: 1.5%; Clavien 4b: 0.1%). Late
      Clavien 3b complications occurred in 4.7% of patients-most of them anastomotic
      strictures. Mortality was 0.1% (Clavien 5). There was a significant decrease in
      overall complication rates over time, resulting predominantly from decreasing
      Clavien 1-2 events. Learning curves of third-generation surgeons plateaued
      earlier compared to the first generation (250 vs 700 cases). The limitation of
      this study is that data concerning comorbidity were not included. CONCLUSIONS:
      LRP is a safe procedure characterised by an acceptable profile of complications.
      Specifically, few major complications are reported. According to the complication
      rates, the learning curve of third-generation surgeons is significantly shorter
      compared to first- and second-generation surgeons.

PMID- 20800342
TI  - Pain is common in Parkinson's disease.
AB  - OBJECTIVE AND BACKGROUND: Patients with Parkinson's disease may present with
      severe or intractable pain, which can be more distressing than the motor
      disability. The aim of this prospective study was to assess the prevalence of
      pain and underlying causes in patients with idiopathic Parkinson's disease.
      PATIENTS AND METHODS: Ninety-six patients (42 female, 54 men) were interviewed
      and pain was assessed using patient descriptions, Visual Analog Scale (VAS) and
      Leeds Assessment of Neuropathic Symptoms and Signs (LANSS). Stait Trait Anxiety
      Inventory (STAI-TX 1 and 2) and Beck Depression Scale were also administered.
      RESULTS: Pain as the first symptom of PD was seen in 3 patients (2.8%), 63
      (64.9%) out of 96 patients reported pain. Pain types included musculoskeletal
      type of different etiologies (28 patients, 44.4%), radicular or neuropathic pain
      (7 patients, 11.1%), pain secondary to dystonia (12 patients, 19.1%) and central
      pain (8 patients, 12.7%). Eight patients (12.7%) described more than one type of
      pain. Pain did not correlate with sex, duration of disease, disease stage, use of
      dopamine agonists and levodopa, years of levodopa treatment and current levodopa
      dosage, depression, anxiety, sleep disturbances, age at onset of PD or history of
      disease in first-degree relatives. Akathisia seemed to be correlated with
      presence of pain (p<0.02). CONCLUSIONS: Our results suggest that pain is one of
      the most common non-motor symptoms in patients with PD. In order to identify the
      appropriate treatment strategy, it is essential to identify the underlying
      etiology.

PMID- 20800343
TI  - Presentation of reversible posterior leukoencephalopathy syndrome in patients on
      calcineurin inhibitors.
AB  - BACKGROUND: Reversible posterior leukoencephalopathy syndrome (RPLS) is a clinico
      radiologic diagnosis associated with numerous medical conditions including
      hypertension, immunosuppressant medications, and eclampsia. It is characterized
      by headache, altered mental status, seizures, visual disturbance, and
      neuroimaging consistent with posterior-predominant vasogenic edema. The objective
      of this study was to characterize the clinical spectrum and outcomes in a large
      series of RPLS patients, and to compare the presentation of patients taking
      calcineurin inhibitors (CNIs) to that of other RPLS patients. METHODS: We
      reviewed records of patients seen by the neurology and transplant services over
      an 18-year period. Comorbid conditions, medications, blood pressure, laboratory
      testing, clinical outcomes, and radiographic findings were collected. RESULTS: 84
      episodes of RPLS were identified in 79 patients. Etiologies included CNIs (43%),
      hypertension (29%), renal disease (12%), preeclampsia/eclampsia (7%), and
      chemotherapy (5%). Patients on CNIs had lower blood pressures (p=0.002) and a
      lower prevalence of headache (p=0.02) compared to RPLS patients with other
      etiologies. Clinical recovery occurred in 65% of episodes, and radiographic
      resolution occurred in 67%. CONCLUSIONS: Patients with CNI-induced RPLS have
      lower blood pressure than other RPLS patients, but otherwise present similarly.
      RPLS typically occurs within days to weeks of CNI initiation in patients without
      elevated medication levels. Clinical and radiographic recovery occurred in the
      majority of patients in this series, but one-third suffered residual neurologic
      deficits or death. These findings highlight the importance of prompt recognition
      and treatment of RPLS triggers to prevent permanent sequelae.

PMID- 20800344
TI  - Botox transient treatment of tinnitus due to stapedius myoclonus: case report.
AB  - OBJECT: To explore the feasibility of using botulinum toxin type A (BTXA) to
      treat tinnitus due to stapedius myoclonus. METHOD: A piece of gelfoam containing
      BTXA (25 U/ml) was placed, through a perforation in tympanic membrane, into the
      middle ear cavity of a patient suffering from tinnitus due to stapedius
      myoclonus. RESULTS: The tinnitus disappeared on the second day after the BTXA
      treatment. The patient was free of symptoms during a 3-month follow-up period.
      Tinnitus reappeared at 4 months, and disappeared after second BTXA local
      treatment. CONCLUSION: Local BTXA treatment may be considered as a treatment for
      tinnitus caused by stapedius myoclonus.

PMID- 20800345
TI  - Prevalence of non-motor dysfunction among Parkinson's disease patients from a
      tertiary referral center in Mexico City.
AB  - Data on the frequency of non-motor symptoms among patients with Parkinson's
      disease (PD) in Mexico has not been reported. OBJECTIVE: To study the prevalence
      of these symptoms in a sample of Mexican PD patients attending a referral
      neurologic center using the Non Motor Symptoms Questionnaire (NMSQuest) and the
      Non Motor Symtpoms Scale (NMSS). METHODS: One-hundred consecutive PD patients, of
      all ages and disease severity were included in a cross-sectional design study.
      The NMSQuest and NMSS were applied during the "on" state. RESULTS: Sample had a
      mean age of 64.5+/-10.9 years and disease duration of 6.6+/-4.8 years. Total
      NMSQuest median score was 10 and the mean NMSS score was 69.3+/-56.7. Positive
      answers classified by domain were as follows: gastrointestinal symptoms 30%,
      urinary symptoms 60%, memory/attention/apathy 39%, hallucinations/delusions 16%,
      depression/anxiety 55%, sexual dysfunction 30%, cardiovascular symptoms 35%,
      sleep disorders 40% and miscellany 27%. CONCLUSION: The prevalence of non-motor
      symptoms among mexican patients with PD is similar to other countries. Mood,
      cognitive and perceptual symptoms seems to be more severe in our population.

PMID- 20800346
TI  - Late-onset CMT2 associated with a novel missense mutation in the cytoplasmic
      domain of the MPZ gene.
AB  - Phenotypic variations have been reported in Charcot-Marie-Tooth disease type 2
      (CMT2) including age-at-onset, disease progression and severity. Sporadic cases
      with CMT2 have also been demonstrated by genetic test. We here report a patient
      with late-onset CMT2 without family history, who developed gait disturbance at
      the age of 68. Sequence analysis revealed a novel heterozygous Arg198Gly mutation
      in the cytoplasmic domain of the major peripheral myelin protein zero (MPZ). The
      mutation is located in the protein kinase C (PKC) alpha substrate motif (RSTK) of
      MPZ, presumably leading to the loss of PKC-mediated phosphorylation in adhesion.
      Routine genetic test for CMT is not recommended for every patient with late-onset
      peripheral neuropathy without known causes, however, the genetic test may be
      taken into consideration if the patient shows a clinical phenotype similar to
      that of CMT, and the possibility of a de novo mutation cannot be excluded.

PMID- 20800347
TI  - Facile preparation of magnetic carbonaceous nanoparticles for Pb2+ ions removal.
AB  - Magnetic carbonaceous nanoparticles were prepared by a facile two-step solution
      phase thermal synthesis. Magnetic nanoparticles (MNPs) with size less than 100 nm
      were first generated from FeCl(3) in a solvothermal reaction. The size could be
      significantly reduced to approximately 30 nm when 1,6-hexanediamine was employed
      in the reaction solution to functionalize the surface of MNPs with amine. Both
      the plain and amine-functionalized MNPs (MH) were effectively encapsulated in the
      carbonaceous shell by hydrothermal treatment in 0.5 M glucose solution. The
      saturation magnetization of MH decreased significantly from 70 to 25 emu/g after
      carbonaceous shell was formed. The as-prepared magnetic carbonaceous
      nanoparticles (MH@C) carries a negative surface charge (-30 mV) at neutral pH and
      has a point of zero charge (PZC) at pH 2. The carbonaceous shell not only can
      protect the magnetic nanoparticles (MNP) from the corrosive environment but also
      possesses a high adsorption capacity towards Pb(II). The adsorption isotherm at
      room temperature can be well-fitted by Langmuir model with a maximum adsorption
      capacity of 123 mg/g.

PMID- 20800348
TI  - A new approach to increasing the efficiency of low-pH Fe-electrocoagulation
      applications.
AB  - Incomplete oxidation of Fe(II) species released from the anode to Fe(III) may
      impede iron electrocoagulation processes conducted under low dissolved oxygen
      and/or pH<7 conditions, accompanied by the typically high buffering capacity of
      wastewater. This paper introduces a new approach to overcome this drawback by
      applying a second electrochemical cell (Ti/RuO(2) anode and Ti cathode) to be
      operated in parallel to the electrocoagulation cell. The second unit oxidizes Cl(
      ) ions invariably present in the water to HOCl, which is capable of oxidizing
      Fe(II) species at a high rate, irrespective of pH or O(2(aq)) concentration. An
      electrolytic cell with a Ti/RuO(2) anode and Ti cathode was shown to successively
      operate in parallel to a sacrificial electrocoagulation cell (Fe anode and Ti
      cathode) to attain complete Fe(II) conversion to Fe(III) under low-pH conditions,
      in which, in the absence of the 2nd cell, unwanted Fe(II) species would have
      dominated the dissolved iron species. Current efficiency for Cl(2) production was
      12.4% and 45.7% at 200 and 1000 mg Cl/l, respectively. Under three practical
      conditions (pH 6, [Cl(-)]=200 mg/l; pH 6, [Cl(-)]=400 mg/l; pH 5, [Cl(-)]=600
      mg/l) the power demand of the combined system was 25.29, 12.7 and 8.1 kWh/kg
      Fe(III)(produced), respectively, suggesting that the presented approach is
      competitive at [Cl(-)]>~600 mg/l.

PMID- 20800349
TI  - Decontamination of Yperite using mesoporous mixed metal oxide nanocrystals.
AB  - Mixed metal oxide nanocrystals of AP-Al(2)O(3), AP-Al(2)O(3)-Fe(2)O(3), AP
      Al(2)O(3)-V(2)O(5) and AP-Al(2)O(3)-CuO have been prepared by aerogel process.
      XRD data of prepared materials revealed the formation of nanocrystals with a size
      range of 3-15 nm diameters. N(2) BET investigations on these materials revealed
      larger values of surface area ranging from 350 to 540 m(2)/g. Reactivity of these
      nanocrystalline materials against Yperite was examined by gas chromatography, gas
      chromatography-mass spectrometry and infrared spectroscopy techniques. AP
      Al(2)O(3)-Fe(2)O(3), AP-Al(2)O(3)-V(2)O(5) and AP-Al(2)O(3)-CuO nanocrystals
      exhibited superior decontamination properties against Yperite than AP-Al(2)O(3).
      The reactions exhibited pseudo first order behaviour. 100% of Yperite was found
      to be decontaminated on Al(2)O(3)-Fe(2)O(3), Al(2)O(3)-V(2)O(5) and Al(2)O(3)-CuO
      where only 75% of the same was found to be decontaminated on AP-Al(2)O(3) within
      40 h.

PMID- 20800350
TI  - Photodegradation of organic dyes in the presence of [Fe(III)-salen]Cl complex and
      H2O2 under visible light irradiation.
AB  - Photodegradation of persistent organic dyes (Rhodamine B (RhB), Malachite Green
      Oxalate (MG) and Crystal Violet 10B (CV)) is studied with Fe(III)-salen complex
      (lambda(max) 494 nm), and hydrogen peroxide under visible light irradiation
      (lambda>=400 nm). The complete decolourization of the dyes (60 mg/L each) was
      achieved in the aqueous medium. The pseudo-first-order degradation rate constants
      of RhB, MG, CV were found to be 2.83*10(-3) s(-1), 1.57*10(-3) s(-1) and 1.34*10(
      3) s(-1), respectively. The effect of various parameters like concentration of
      H(2)O(2), pH of the medium, and influence of electrolytes are investigated on the
      degradation of RhB. A modified benzoic acid hydroxylation method has been used to
      detect the active oxygen species (OH radicals) in this study. The hydroxyl
      radical production is increased with the increase in irradiation time.
      Interestingly, even an excess amount of scavenger could not arrest the
      degradation of the dyes. This may be due to the formation of some secondary
      oxidants. Here, active ferryl ion was identified as the secondary oxidant.
      Degradation products of the dye (RhB) were determined by GC-MS, and phthalic acid
      was identified as the major one. From the results, a possible photodegradation
      mechanism has been proposed.

PMID- 20800351
TI  - Two important factors influencing shock sensitivity of nitro compounds: Bond
      dissociation energy of X-NO2 (X = C, N, O) and Mulliken charges of nitro group.
AB  - DFT/BLYP/DNP is employed to calculate bond dissociation energy of X-NO(2) (X = C,
      N, O) and Mulliken charges of nitro group of 14 kinds of nitro compounds, and
      partial least squares approximation is applied to linearly fit their shock
      initiation pressure (p(90%,TMD)). It is found that the fitted values are in good
      agreement with the experimental shock initiation pressures. The fitted model is
      used to predict the shock initiation pressures of two kinds of explosives, TNB
      and TNETB. The predictive values are in accordance with experimental ones. It
      reflects that bond dissociation energy of X-NO(2) (X = C, N, O) and Mulliken
      charge of nitro groups may be the important factors influencing the shock
      sensitivity of nitro compounds. On the basis of the fitted model, bond
      dissociation energy of X-NO(2) (X = C) and Mulliken charges of nitro groups of
      another 14 kinds of heterocyclic nitro compounds are in consideration to predict
      shock sensitivity. This work is meaningful in further understanding the shock
      mechanism and helpful to the design and synthesis of novel energetic materials.

PMID- 20800352
TI  - Photocatalytic activity of silver vanadate with one-dimensional structure under
      fluorescent light.
AB  - One-dimensional beta-AgVO(3) nanobelts (SVN) were realized by a facile
      hydrothermal method. It indicates the anisotropic crystallographic
      characteristics through the characterization. With the additive PEG, the sample
      was restrained in the one-dimensional preferential orientation (SV-P)
      effectively. The photocatalytic activity studies reveal that the photocatalyst
      beta-AgVO(3) exhibits excellent photocatalytic activity in the inactivation of
      Escherichia coli under fluorescent light. In addition, it is found that the
      morphology has effect on the photocatalytic activity. The beta-AgVO(3)
      photocatalyst with one-dimensional structure has the potential and promising
      application in bacterial disinfection indoor using fluorescent light.

PMID- 20800353
TI  - The adsorption properties of Pb(II) and Cd(II) on functionalized graphene
      prepared by electrolysis method.
AB  - The functionalized graphene (GNS(PF6)) was fabricated by simple and fast method
      of electrolysis with potassium hexafluorophosphate solution as electrolyte under
      the static potential of 15 V. The characterization results of transmission
      electron microscopy, atom force microscopy, X-ray photoelectron spectroscopy, X
      ray powder diffraction, Raman spectroscopy and thermogravimetric analysis
      indicate that graphite rod was completely exfoliated to graphene layer containing
      30 wt.% PF(6)- with the average thickness ca. 1.0 nm. Our sample of GNS(PF6) was
      developed for the removal of Pb(II) or Cd(II) ions from water, and the determined
      adsorption capacities are 406.6 mg/g (pH=5.1) for Pb(II) and 73.42 mg/g (pH=6.2)
      for Cd(II), which is much higher than that by our previous sample of GNS(C8P) and
      carbon nanotube. The adsorption processes reach equilibrium in just 40 min and
      the adsorption isotherms are described well by Langmuir and Freundlich classical
      isotherms models.

PMID- 20800354
TI  - Leaching of copper and tin from used printed circuit boards after thermal
      treatment.
AB  - The hydrometallurgical route of copper and tin extraction from printed circuit
      boards (PCBs) of used personal computers after thermal pretreatment is discussed.
      The samples were thermally pretreated within temperature range of 300-900 degrees
      C during 15, 30 and 60 min. Two methods of the thermal pretreatment were studied:
      burning and pyrolysis. The leaching solution of 1 M HCl at 80 degrees C was used.
      The original as well as thermally pretreated samples were leached. The weight
      losses within the range from 5 to 35% were achieved. The increase of burning
      temperature causes the copper extraction into solution up to 98%, while copper
      extraction into solution from non-burned samples was up to 6%. In the case of the
      tin leaching the highest extraction was achieved when the original sample was
      leached. The increase of the burning temperature caused the lowering of the
      copper extraction. The increase of the pyrolysis temperature enhances copper and
      tin extraction.

PMID- 20800355
TI  - Ageing behavior of phenanthrene and pyrene in soils: a study using sodium
      dodecylbenzenesulfonate extraction.
AB  - The surfactant SDBS has potential to be used as an extractant in advanced
      extraction methods. It was investigated if SDBS in concentrations of 10,000 mg L(
      1) can be used to study the ageing behaviors of phenanthrene and pyrene in two
      soils. Compared to dichloromethane extraction, extraction with 10,000 mg L(-1)
      SDBS can improve the precision of the determination due to the low volatility of
      surfactant solution. In all cases tested, the amount of sorbed phenanthrene and
      pyrene in soils increased with contact time from 1 to 120 days, and can be
      applied well to both the three-domain model and the dual mode model. Redundancy
      analysis showed that time, organic carbon content and logK(ow) are major factors
      affecting the fitted Freundlich parameters and the sorption kinetics of
      phenanthrene and pyrene. The amount of sorbed phenanthrene and pyrene in low
      concentrations samples varied more with time than the one in high concentrations,
      indicating that the sorption on soils is concentration-dependent. Also, the
      isotherms were operationally separated into a "fast" fraction and a "slow"
      fraction. The results imply that the adsorption sites are internal to the SOM
      matrix and unevenly distributed.

PMID- 20800356
TI  - Mildly negative social encounters reduce physical pain sensitivity.
AB  - While previous research has demonstrated a reduction in physical pain sensitivity
      in response to social exclusion, the manipulations employed have arguably been
      far removed from typical daily experience. The purpose of this study was to
      investigate the effects of relatively ordinary social encounters on the
      perception of pain. Healthy participants rated the intensity and unpleasantness
      of painful stimuli before and after engaging in a structured interaction with a
      confederate who was instructed to either be warm and friendly or indifferent. A
      control group was asked to perform a similar structured activity, but alone.
      Consistent with predictions, participants who experienced the mildly negative
      social exchange reported lower pain intensity and unpleasantness after the
      encounter relative to baseline, whereas those exposed to the positive social
      exchange did not evidence any change in pain ratings. These results were not
      mediated by changes in mood or perceived connectedness. If mildly negative social
      encounters can provoke an analgesic effect, it is possible that social
      hypoalgesia may be considerably more commonplace than previously realized.
      Discussion focuses on the role of stress-induced hypoalgesia, and the
      implications of the results for clinical assessments of pain.

PMID- 20800359
TI  - Psychological approaches are effective for fibromyalgia: remaining issues and
      challenges.

PMID- 20800358
TI  - A multicenter, placebo-controlled, double-blind, multiple-crossover study of
      Fentanyl Pectin Nasal Spray (FPNS) in the treatment of breakthrough cancer pain.
AB  - This randomized, double-blind, crossover study assessed the efficacy and
      tolerability of a new rapid onset nasal fentanyl formulation (Fentanyl Pectin
      Nasal Spray; FPNS) for breakthrough cancer pain (BTCP). Eighty-three of 114
      patients experiencing one to four BTCP episodes/day while taking >=60 mg/day of
      oral morphine or equivalent successfully identified an effective dose of FPNS
      during a titration phase and entered a double-blind phase in which 10 BTCP
      episodes were treated with this effective dose (7) or placebo (3). Compared with
      placebo, FPNS significantly improved mean summed pain intensity difference (SPID)
      from 10 min (P<0.05) until 60 min (P<0.0001), including the primary endpoint at
      30 min (P<0.0001). FPNS significantly improved pain intensity (PI) scores as
      early as 5 min (P<0.05); pain intensity difference (PID) from 10 min (P<0.01);
      and pain relief (PR) scores from 10 min (P<0.001). More patients showed a
      clinically meaningful (>= 2-point reduction in PI) pain reduction from 10 min
      onward (P <= 0.01) and 90.6% of the FPNS-treated versus 80.0% of placebo-treated
      BTCP episodes did not require rescue medication (P<0.001). Approximately 70% of
      patients were satisfied or very satisfied with the convenience and ease of use of
      FPNS. Only 5.3% of patients withdrew from treatment due to adverse events, no
      significant nasal effects were reported, and 87% of patients elected to continue
      open-label treatment post-study. In this short-term study, FPNS was safe, well
      tolerated, and rapidly efficacious for BTCP.

PMID- 20800357
TI  - Neuropathic pain-like alterations in muscle nociceptor function associated with
      vibration-induced muscle pain.
AB  - We recently developed a rodent model of the painful muscle disorders induced by
      occupational exposure to vibration. In the present study we used this model to
      evaluate the function of sensory neurons innervating the vibration-exposed
      gastrocnemius muscle. Activity of 74 vibration-exposed and 40 control
      nociceptors, with mechanical receptive fields in the gastrocnemius muscle, were
      recorded. In vibration-exposed rats ~15% of nociceptors demonstrated an intense
      and long-lasting barrage of action potentials in response to sustained
      suprathreshold mechanical stimulation (average of 2635 action potentials with
      frequency of ~44Hz during a 1min suprathreshold stimulus) much greater than that
      has been reported to be produced even by potent inflammatory mediators. While
      these high-firing nociceptors had lower mechanical thresholds than the remaining
      nociceptors, exposure to vibration had no effect on conduction velocity and did
      not induce spontaneous activity. Hyperactivity was not observed in any of 19
      neurons from vibration-exposed rats pretreated with intrathecal antisense for the
      IL-6 receptor subunit gp130. Since vibration can injure peripheral nerves and IL
      6 has been implicated in painful peripheral neuropathies, we suggest that the
      dramatic change in sensory neuron function and development of muscles pain,
      induced by exposure to vibration, reflects a neuropathic muscle pain syndrome.

PMID- 20800360
TI  - Evolving strategies for the treatment of hepatocellular carcinoma: from clinical
      guided to molecularly-tailored therapeutic options.
AB  - Hepatocellular carcinoma (hepatocellular carcinoma, HCC) is the commonest primary
      liver cancer (80-90%) and represents the leading cause of cancer-related death,
      after lung and stomach cancer. The process of neoplastic transformation proceeds
      through the accumulation of mutations in the genes governing cell proliferation
      and apoptosis. It is currently difficult to determine the natural history of
      patients with untreated early-stage HCC, since most with early-stage tumor
      patients undergoes curative therapy. Survival rates at 3 years is 65% in patients
      with Child-Pugh A, and single untreated lesion. This proportion increases to 70%
      at 5 years after radical treatment. In patients included in randomized controlled
      clinical trials with advanced disease, survival at 1 and 2 years is respectively
      72% and 50%. Surgery is the only potentially curative treatment for HCC. In
      carefully selected patients, resection and transplantation in fact, allow a 5
      years survival from 60% to 70%. Unfortunately most patients in Western countries
      present with an intermediate or advanced HCC at diagnosis with the consequent
      inability to use curative treatments. These patients are therefore candidates to
      palliative therapies that include arterial embolization and chemoembolization and
      systemic treatments including chemotherapy, immunotherapy and hormonal therapy.
      Only recently the molecular targeted drug, Sorafenib, has been introduced among
      the therapeutic options for these patients.

PMID- 20800361
TI  - Acute stress impairs memory retrieval independent of time of day.
AB  - It is widely recognized that acute stress and associated glucocorticoid stress
      responses yield memory-enhancing effects when the memory consolidation phase is
      targeted, while impairing effects are generally found with regard to memory
      retrieval performance. While some evidence exists that the memory-enhancing
      effects of consolidation stress are modulated by time of day, no study to date
      has investigated whether stress-induced retrieval deficits are also prone to such
      time of day effects. To address this issue, participants (N=76) were exposed to a
      stressor or control condition before a retrieval test that probed for neutral and
      negative words learned 24h before. Results show that stress exposure resulted in
      impaired retrieval of both neutral and negative words, but that time of day did
      not moderate this effect. This memory-impairing effect was larger for negative
      than for neutral information, and was significantly associated with stress
      induced cortisol responses. The current findings demonstrate the robustness of
      stress-induced retrieval deficits throughout the day, in particular for emotional
      memory material, and further underscore the importance of cortisol reactivity in
      impairing memory retrieval.

PMID- 20800362
TI  - Chronic immune stimulation as a contributing cause of chronic disease in opiate
      addiction including multi-system ageing.
AB  - Evidence of immune stimulation has been noted in opiate dependent patients for
      many decades. Documented changes have included lymphadenopathy, round cell
      infiltration of the hepatic portal triads, diffuse peri-bronchitis,
      hyperglobulinaemia, lymphocytosis, monocytosis, systemic cytokine stimulation,
      and cytokine and chemokine activation within the neuraxis. A parallel literature
      describes an elevated list of chronic degenerative disease as common in such
      patients including neurodegenerative conditions, atherosclerosis,
      nephrosclerosis, hepatic fibrosis and cirrhosis, chronic obstructive and fibrotic
      lung disease, osteoporosis, chronic periodontitis, various cancers, hair greying,
      and stem cell suppression. All of these disorders are now known to have an
      important immunological role in their pathogenic pathways. The multisystem nature
      of these myriad changes strongly suggest that the ageing process itself is
      stimulated in these patients. The link between the immunostimulation on the one
      hand and the elevated and temporally advanced nature of the chronic degenerative
      diseases on the other appears not to have been made in the literature. Moreover
      as immunostimulation is also believed to be an important, potent and principal
      contributor to the ageing process it appears that experimental and studies of
      this putative link are warranted. Verification of such an hypothesis would also
      carry management implications for dose and duration of chronic pain and addiction
      treatment, pharmacotherapeutic selection, and novel treatments such as long term
      naltrexone implant therapy and heroin trials.

PMID- 20800363
TI  - Dental follicle cells combined with beta-tricalcium phosphate ceramic: a novel
      available therapeutic strategy to restore periodontal defects.
AB  - Tissue-engineering strategies to restore the periodontal defects are being
      developed. It will result in the periodontal formation and growing new function
      tissue rather than new replacement of periodontium. Although a number of
      procedures have been investigated in an attempt to regenerate lost periodontal
      tissue, none has yet led to new cementum formation, remodeling of the periodontal
      ligament, and new bone formation in clinic. Dental follicle cells (DFCs), as a
      progenitor cell of periodontal ligament cell and stem cell, have more potential
      abilities than PDL-cell in formation of periodontal tissue. More researches focus
      on the inductive environments, such as bone morphogenetic protein-2 (BMP-2),
      dexamethasone, and transfer growth factor, and scaffold. We hypotheses that DFCs
      from Beagle's dog are isolated, induced by BMP-2, basic-fibroblast growth factor
      and dexamethasone, and seeded by beta-tricalcium phosphate ceramic (beta-TCP),
      then the complex was auto-implanted into the periodontal defects in the same
      Beagle's dog to observe the regeneration of periodontal tissue in vivo. The study
      will explore the feasibility and application of restore of periodontal defects by
      DFCs-beta-TCP complex. We believe it is especially helpful to future clinical
      study and application.

PMID- 20800364
TI  - Eppin, a novel marker to differentially diagnose azoospermia?

PMID- 20800365
TI  - Culturing functional cartilage tissue under a novel bionic mechanical condition.
AB  - Bioreactor, which is used for in vitro construction of tissue-engineered
      cartilage, has been extensively studied by researchers. The growth and
      development of articular cartilage tissue are affected by biomechanical and
      biochemical factors, especially mechanical condition. Kinds of mechanical
      conditions including compressive and shear force, fluid flow, hydrostatic
      pressure, and tissue deformation, were developed in the past years. However, most
      mechanical conditions of improved bioreactor involve only one or two external
      force, which is merely partial for engineering cartilage tissue. No bioreactor
      which can simulate a normal articular cartilage in terms of structure and
      function has been reported. Consequently, simulation of bionic mechanical
      environment of a normal articular cartilage is considered to be the optimal
      environment for culturing the functional articular cartilage in vitro. Based upon
      this purpose, we designed a rolling-compression loading bioreactor. It could
      provide cultures with multi-mechanical stimulations and sufficiently mimic the
      complex mechanical environment of a normal articular cartilage. We propose that
      this comprehensive rolling-compression loading bioreactor can enhance the
      cultivation of functional cartilage constructs in vitro.

PMID- 20800366
TI  - Baseline event rate, the Concorde fallacy, and the topography of cardiac risk.
AB  - Cardiac risk stratification is the attempt to delineate who is at risk of cardiac
      event and who is not. Increasingly, the medical literature is filled with novel
      methods and markers of baseline risk assessment. This body of literature has been
      criticized broadly for making claims beyond what is statistically justified. In
      this hypothesis, we will explore an alterative explanation for the limitations of
      baseline risk assessment. I will contend that current risk models commit a
      logical error called the Concorde fallacy. The role of risk topography will be
      suggested as a novel method to rescue cardiac risk models.

PMID- 20800367
TI  - Transient oncogenes.
AB  - A given cancer is produced by a unique combination of genetic alterations that
      target specific genes, most often leading to activation of oncogenes and
      inactivation of tumor suppressor genes. Traditional oncogenes, such as RasV12,
      are involved in maintaining pro-survival and proliferation signals activated in
      the cell. Several evidences suggest that cancer cells are addicted to oncogenes
      and that their inhibition has dramatic effects on cancer cells. Here, the
      hypothesis that oncogenes may be activated only transiently and that this short
      activation may be important for cancer formation by affecting the differentiation
      state of the cancer cells is presented. These "transient oncogenes" are
      overlooked in genomic or proteomic analysis due to their transient nature. Here
      we argue that transcription factors, such as the so called Yamanaka factors,
      capable of reprogramming cells to a less differentiated state, which normally
      happens to cancer cells, can function as transient oncogenes. Several published
      evidences are used to support the proposed hypothesis. Analysis and even
      targeting of this new class of oncogenes could have a great impact on cancer
      biology, treatment and, most importantly, prevention.

PMID- 20800368
TI  - Morquio disease: the role of cartilage canals in the pathogenesis of chondrogenic
      dwarfism.
AB  - Chondrogenic dwarfism in Morquio disease (mucopolysaccharidosis IV) has been
      suggested to be strongly linked to the abnormal lysosomal storage of
      cartilaginous extracellular matrix waste products within chondrocytes and
      fibroblasts. The specific genetic defects of enzymes of the keratan sulfate and
      chondroitin-6-sulfate metabolism have been detected at the molecular level and
      importantly contributed to the current knowledge on the phenotype of this rare
      metabolic disorder. However, the pathogenesis of this epiphyseal centered
      progressive skeletal disease does not seem to be fully explained by the
      dysfunction of the chondrocyte cytoplasm that presents with vacuolar changes in
      adult patients. I propose that the accumulation of extracellular matrix
      degradation product-laden macrophages within epiphyseal cartilage canals during
      the early postnatal period causes dysregulation in the synchronized process of
      the neoformation and resorption of the maturing radial growing epiphyses.
      Similarly, the resorption of pannus tissue following the microtraumatisation of
      weight-bearing joints and epiphysis-type bones becomes impacted. If the
      hypothesis is valid, the early pathogenesis in Morquio disease could be because
      of the inadequate regression of cartilage canals and impaired resorption and
      restitution of pannus tissue.

PMID- 20800369
TI  - Moderate levels of plasma uric acid could promote fracture healing.

PMID- 20800370
TI  - Sleep impairment during pregnancy: possible implications on mother-infant
      relationship.
AB  - The modern living standard has imposed upon society a situation of chronic sleep
      deprivation. This chronic loss of sleep affects women more than it does men. As a
      result, the postponement of pregnancy has become a common choice due to the
      priority given to social and domestic activities. For women, pregnancy represents
      a condition of intense physical and physiological changes that subject the
      pregnant woman to a number of potentially stressful situations, ultimately
      interfering with their quality of sleep. Chronic sleep deprivation, along with
      the changes imposed on women through pregnancy, can lead to several harmful
      consequences for the pregnant woman and the child, and can potentially undermine
      the mother-infant relationship. This article discusses circumstances under which
      sleep deprivation and poor sleep quality during pregnancy could result in damage
      to the mother-infant relationship, specifically through maternal fatigue,
      postpartum depression and changes in pregnancy-related hormonal secretions and
      activity.

PMID- 20800371
TI  - Evaluation of stored lamb bio-preserved using a three-strain cocktail of
      Lactobacillus sakei.
AB  - Commercially prepared lamb was stored at -1.5  degrees C after inoculation with a
      combination of three Lactobacillus sakei strains previously shown to inhibit
      spoilage and pathogenic bacteria of importance to the meat industry. Between 6
      and 14 weeks storage samples were evaluated for growth of inoculated strains,
      production of fermentation end-products and sensory acceptance of the cooked
      product. All three L. sakei strains flourished during storage, formed
      consistently dominant populations and were associated with lower surface pH and
      increased levels of lactic and acetic acids. Inoculated samples were determined
      to be as equally acceptable for smell, acidity, rancidity and overall liking as
      un-inoculated controls.

PMID- 20800372
TI  - Changes in the bacterial communities of vacuum-packaged pork during chilled
      storage analyzed by PCR-DGGE.
AB  - In this study, PCR-denaturing gradient gel electrophoresis (DGGE) was used to
      investigate the bacterial communities of vacuum-packaged pork during chilled
      storage. Eight kinds of lactic acid bacteria (LAB) were identified from the
      strains isolated from MRS plates by PCR-DGGE of the V3 region, and Lactobacillus
      sakei was the representative isolate at the end of the monitoring. By means of
      the direct meat analysis of PCR-DGGE, LAB increased gradually and Carnobacterium
      sp./Car. divergens, Lactobacillus sakei and Lactococcus sp./Lc. piscium, became
      the predominant bacteria at the end of the storage. The results of Lactobacillus
      specific PCR and DGGE showed that different Lactobacillus populations were
      present at different storage periods and Lb. sakei became the predominant
      bacteria in the end. In conclusion, the PCR-DGGE technique as a culture
      independent method is applicable to monitoring bacterial population dynamics in
      vacuum-packaged pork.

PMID- 20800373
TI  - Parametrial boost using midline shielding results in an unpredictable dose to
      tumor and organs at risk in combined external beam radiotherapy and brachytherapy
      for locally advanced cervical cancer.
AB  - PURPOSE: Midline-blocked boost (MBB) fields are frequently used in the treatment
      of locally advanced cervical cancer. The purpose of this study was to evaluate
      the dose contribution from MBBs to tumor and organs at risk. METHODS AND
      MATERIALS: Six patients with locally advanced cervical cancer (IIB-IIIB) treated
      with definitive chemoradiotherapy and magnetic resonance imaging (MRI)-guided
      brachytherapy were analyzed. A three-phase plan was modeled: 45 Gy (1.8 Gy per
      fraction) four-field box, 9 Gy (1.8 Gy per fraction) MBB (midline-shielded
      anteroposterior/posteroanterior fields), and intracavitary MRI-guided
      brachytherapy boost of 28 Gy (7 Gy per fraction). Midline shields 3, 4, and 5 cm
      wide were simulated for each patient. Brachytherapy and MBB plans were
      volumetrically summed. The rectum, sigmoid, and bladder minimum dose in the most
      exposed 2 cm(3) of an organ at risk (D(2 cc)) and high-risk clinical target
      volume (HR-CTV) and intermediate-risk clinical target volume (IR-CTV) D90 and
      D100 were evaluated. The intended HR-CTV D90 was 85 Gy or greater, and the
      intended IR-CTV D90 was greater than 60 Gy. RESULTS: After a 4-cm MBB, HR-CTV D90
      remained lower than 85 Gy in all cases (mean, 74 Gy; range, 64-82 Gy). High-risk
      clinical target volume (85 Gy) coverage increased slightly from 73% (range, 64
      82%) to 78% (range, 69-88%). Mean IR-CTV D90 increased from 56 Gy (range, 53-64
      Gy) to 62 Gy (range, 59-67 Gy). Intermediate-risk clinical target volume 60-Gy
      dose coverage increased from 81% (range, 72-96%) to 96% (range, 90-100%). The
      mean volume irradiated to 85 Gy increased by 14 cm(3) (range, 10-22 cm(3)),
      whereas the volume irradiated to 60 Gy increased from 276 cm(3) (range, 185-417
      cm(3)) to 592 cm(3) (range, 385-807 cm(3)). Bladder, rectum, or sigmoid D(2 cc)
      increased by more than 50% of the boost dose in 4 of 6 patients. CONCLUSIONS:
      Midline-blocked boosts contribute substantial dose to rectum, sigmoid, and
      bladder D(2 cc). HR-CTV dose and 85-Gy coverage remain compromised in large
      tumors despite MBB. IR-CTV 60-Gy coverage improved at the expense of a
      considerable increase in volume of normal tissue irradiated to 60 Gy.

PMID- 20800374
TI  - Accelerated partial breast irradiation for pure ductal carcinoma in situ.
AB  - PURPOSE: To report outcomes for ductal carcinoma in situ (DCIS) treated with
      breast-conserving therapy using accelerated partial breast irradiation (APBI).
      METHODS AND MATERIALS: From March 2001 to February 2009, 53 patients with Stage 0
      breast cancer were treated with breast conserving surgery and adjuvant APBI.
      Median age was 62 years. All patients underwent excision with margins negative by
      >=1 mm before adjuvant radiotherapy (RT). A total of 39 MammoSite brachytherapy
      (MS) patients and 14 three-dimensional conformal external beam RT (3DCRT)
      patients were treated to the lumpectomy bed alone with 34 Gy and 38.5 Gy,
      respectively. Of the DCIS cases, 94% were mammographically detected. All patients
      with calcifications had either specimen radiography or postsurgical mammography
      confirmation of clearance. Median tumor size was 6 mm, and median margin distance
      was 5 mm. There were no statistically significant differences according to APBI
      method for race/ethnicity, tumor detection method, tumor grade, estrogen receptor
      (ER) status, or use of tamoxifen (p = NS). Recurrence and survival were
      calculated using the Kaplan-Meier method. Cosmesis was scored by the Harvard
      criteria. RESULTS: With a median follow-up of 3.6 years (range, 0.4-6.3 years),
      the overall and cause-specific survival rates were 98% and 100%, respectively.
      Three-year actuarial ipsilateral breast tumor recurrence was 2%. One failure was
      observed at the resection bed 11 months post-RT. No other elsewhere breast
      failures, regional recurrences, or distant metastases were noted. Cosmesis was
      excellent or good in 92.4% of cases, with no statistically significant
      differences according to the APBI method (92.3% with MammoSite and 92.8% with
      3DCRT; p = 0.649). CONCLUSIONS: APBI as part of breast-conserving therapy for
      pure DCIS was associated with excellent local control and survival rates, with
      the vast majority of patients having good to excellent cosmesis. This finding
      supports the recent analysis by the American Society of Breast Surgeons on a
      subset of DCIS patients treated efficaciously with APBI.

PMID- 20800375
TI  - Clinical outcome of hypofractionated stereotactic radiotherapy for abdominal
      lymph node metastases.
AB  - PURPOSE: We report the medium-term clinical outcome of hypofractionated
      stereotactic body radiotherapy (SBRT) in a series of patients with either a
      solitary metastasis or oligometastases from different tumors to abdominal lymph
      nodes. METHODS AND MATERIALS: Between January 2006 and June 2009, 19 patients
      with unresectable nodal metastases in the abdominal retroperitoneal region were
      treated with SBRT. Of the patients, 11 had a solitary nodal metastasis and 8 had
      a dominant nodal lesion as part of oligometastatic disease, defined as up to five
      metastases. The dose prescription was 45 Gy to the clinical target volume in six
      fractions. The prescription had to be downscaled by 10% to 20% in 6 of 19 cases
      to keep within dose/volume constraints. The first 11 patients were treated with
      three-dimensional conformal techniques and the last 8 by volumetric intensity
      modulated arc therapy. Median follow-up was 1 year. RESULTS: Of 19 patients, 2
      had a local progression at the site of SBRT; both also showed concomitant tumor
      growth at distant sites. The actuarial rate of freedom from local progression was
      77.8% +/- 13.9% at both 12 and 24 months. Eleven patients showed progressive
      local and/or distant disease at follow-up. The 12- and 24-month progression-free
      survival rates were 29.5% +/- 13.4% and 19.7% +/- 12.0%, respectively. The number
      of metastases (solitary vs. nonsolitary oligometastases) emerged as the only
      significant variable affecting progression-free survival (p < 0.0004). Both acute
      and chronic toxicities were minimal. CONCLUSIONS: Stereotactic body radiotherapy
      for metastases to abdominal lymph nodes was shown to be feasible with good
      clinical results in terms of medium-term local control and toxicity rates. Even
      if most patients eventually show progressive disease at other sites, local
      control achieved by SBRT may be potentially significant for preserving quality of
      life and delaying further chemotherapy.

PMID- 20800376
TI  - Renal shielding and dosimetry for patients with severe systemic sclerosis
      receiving immunoablation with total body irradiation in the scleroderma:
      cyclophosphamide or transplantation trial.
AB  - PURPOSE: To describe renal shielding techniques and dosimetry in delivering total
      body irradiation (TBI) to patients with severe systemic sclerosis (SSc) enrolled
      in a hematopoietic stem cell transplant protocol. METHODS AND MATERIALS: The
      Scleroderma: Cyclophosphamide or Transplantation (SCOT) protocol uses a
      lymphoablative preparative regimen including 800 cGy TBI delivered in two 200-cGy
      fractions twice a day before CD34(+) selected autologous hematopoietic stem cell
      transplantation. Lung and kidney doses are limited to 200 cGy to protect organs
      damaged by SSc. Kidney block proximity to the spinal cord was investigated, and
      guidelines were developed for acceptable lumbar area TBI dosing. Information
      about kidney size and the organ shifts from supine to standing positions were
      recorded using diagnostic ultrasound (US). Minimum distance between the kidney
      blocks (dkB) and the lumbar spine region dose was recorded, and in vivo dosimetry
      was performed at several locations to determine the radiation doses delivered.
      RESULTS: Eleven patients were treated at our center with an anteroposterior
      (AP)/posteroanterior (PA) TBI technique. A 10% to 20% dose inhomogeneity in the
      lumbar spine region was achieved with a minimum kidney block separation of 4 to 5
      cm. The average lumbar spine dose was 179.6 +/- 18.1 cGy, with an average dkB of
      5.0 +/- 1.0 cm. Kidney block shield design was accomplished using a combination
      of US and noncontrast computerized tomography (CT) or CT imaging alone. The renal
      US revealed a wide range of kidney displacement from upright to supine positions.
      Overall, the average in vivo dose for the kidney prescription point was 193.4 +/-
      5.1 cGy. CONCLUSIONS: The dose to the kidneys can be attenuated while maintaining
      a 10% to 20% dose inhomogeneity in the lumbar spine area. Kidneys were localized
      more accurately using both US and CT imaging. With this technique, renal function
      has been preserved, and the study continues to enroll patients.

PMID- 20800377
TI  - Development of late toxicity and International Prostate Symptom Score resolution
      after external-beam radiotherapy combined with pulsed dose rate brachytherapy for
      prostate cancer.
AB  - PURPOSE: To investigate the development of gastrointestinal (GI) toxicity,
      genitourinary (GU) toxicity, erectile dysfunction, and International Prostate
      Symptom Score (IPSS) resolution in a cohort of patients treated with external
      beam radiotherapy (EBRT) followed by a brachytherapy pulsed dose rate (PDR)
      boost. METHODS AND MATERIALS: Between 2002 and 2008, 110 patients were treated
      with 46-Gy EBRT followed by PDR brachytherapy (24.96-28.80 Gy). The investigated
      outcome variables, GI toxicity, GU toxicity, erectile dysfunction, and IPSS were
      prospectively scored at several time points during follow-up. Association between
      time (as continuous and categorical variable) and the outcome variables was
      assessed using generalized linear models. RESULTS: No statistically significant
      association was found between time (continuous) and GI toxicity (odds ratio [OR],
      0.97; 95% confidence interval [CI], 0.89-1.06), GU toxicity (OR, 0.97; 95% CI,
      0.91-1.03), erectile dysfunction (OR, 1.06; 95% CI, 0.99-1.11), and IPSS (-0.11;
      95% CI, -0.41-0.20). Also, no statistically significant association was found
      between these variables and time as a categorical variable. GU toxicity was
      associated with IPSS resolution (OR, 1.16; 95% CI, 1.09-1.24). Posttreatment IPSS
      was associated with pretreatment IPSS (0.52; 95% CI, 0.25-0.79). CONCLUSIONS: No
      accumulation of high-grade toxicity over time could be established for a group of
      patients treated with EBRT and PDR brachytherapy for prostate cancer, probably
      because high-grade late toxicity resolves with time. Also, differences in IPSS
      values among patients are smaller after treatment than before treatment.

PMID- 20800378
TI  - Imaging opportunities in radiation oncology.
AB  - Interdisciplinary efforts may significantly affect the way that clinical
      knowledge and scientific research related to imaging impact the field of
      Radiation Oncology. This report summarizes the findings of an intersociety
      workshop held in October 2008, with the express purpose of exploring "Imaging
      Opportunities in Radiation Oncology." Participants from the American Society for
      Radiation Oncology (ASTRO), National Institutes of Health (NIH), Radiological
      Society of North America (RSNA), American Association of physicists in Medicine
      (AAPM), American Board of Radiology (ABR), Radiation Therapy Oncology Group
      (RTOG), European Society for Therapeutic Radiology and Oncology (ESTRO), and
      Society of Nuclear Medicine (SNM) discussed areas of education, clinical
      practice, and research that bridge disciplines and potentially would lead to
      improved clinical practice. Findings from this workshop include recommendations
      for cross-training opportunities within the allowed structured of Radiology and
      Radiation Oncology residency programs, expanded representation of ASTRO in
      imaging related multidisciplinary groups (and reciprocal representation within
      ASTRO committees), increased attention to imaging validation and credentialing
      for clinical trials (e.g., through the American College of Radiology Imaging
      Network (ACRIN)), and building ties through collaborative research as well as
      smaller joint workshops and symposia.

PMID- 20800379
TI  - The use of the Active Breathing Coordinator throughout radical non-small-cell
      lung cancer (NSCLC) radiotherapy.
AB  - PURPOSE: To assess feasibility and reproducibility of an Active Breathing
      Coordinator (ABC) used throughout radical radiotherapy for non-small-cell lung
      cancer, and compare lung dosimetric parameters between free-breathing and ABC
      plans. METHODS AND MATERIALS: A total of 18 patients, recruited into an approved
      study, had free-breathing and ABC breath-hold treatment plans generated. Lung
      volume, the percentage volume of lung treated to a dose of >=20 Gy (V(20)), and
      mean lung dose (MLD) were compared. Treatment (64 Gy in 32 fractions, 5
      days/week) was delivered in breath-hold. Repeat breath-hold computed tomography
      scans were used to assess change in gross tumor volume (GTV) size and position.
      Setup error was also measured and potential GTV-planning target volume (PTV)
      margins calculated. RESULTS: Seventeen of 18 patients completed radiotherapy
      using ABC daily. Intrafraction tumor position was consistent, but interfraction
      variation had mean (range) values of 5.1 (0-25), 3.6 (0-9.7), and 3.5 (0-16.6) mm
      in the superoinferior (SI), right-left (RL), and anteroposterior (AP) directions,
      respectively. Tumor moved partially outside the PTV in 5 patients. Mean reduction
      in GTV from planning to end of treatment was 25% (p = 0.003). Potentially
      required PTV margins were 18.1, 11.9, and 11.9 mm in SI, RL, and AP directions.
      ABC reduced V(20) by 13% (p = 0.0001), V(13) by 12% (p = 0.001), and MLD by 13%
      (p < 0.001) compared with free-breathing; lung volume increased by 41% (p <
      0.001). CONCLUSIONS: Clinically significant movements of GTV were seen during
      radiotherapy for non-small-cell lung cancer using ABC. Image guidance is
      recommended with ABC. The use of ABC can reduce dose volume parameters
      determining lung toxicity, and might allow for equitoxic radiotherapy dose
      escalation.

PMID- 20800380
TI  - Primary analysis of a phase II randomized trial Radiation Therapy Oncology Group
      (RTOG) 0212: impact of different total doses and schedules of prophylactic
      cranial irradiation on chronic neurotoxicity and quality of life for patients
      with limited-disease small-cell lung cancer.
AB  - PURPOSE: To determine the effect of dose and fractionation schedule of
      prophylactic cranial irradiation (PCI) on the incidence of chronic neurotoxicity
      (CNt) and changes in quality of life for selected patients with limited-disease
      small-cell lung cancer (LD SCLC). METHODS AND MATERIALS: Patients with LD SCLC
      who achieved a complete response after chemotherapy and thoracic irradiation were
      eligible for randomization to undergo PCI to a total dose of 25 Gy in 10 daily
      fractions (Arm 1) vs. the experimental cohort of 36 Gy. Those receiving 36 Gy
      underwent a secondary randomization between daily 18 fractions (Arm 2) and twice
      daily 24 fractions (Arm 3). Enrolled patients participated in baseline and follow
      up neuropsychological test batteries along with quality-of-life assessments.
      RESULTS: A total of 265 patients were accrued, with 131 in Arm 1, 67 in Arm 2,
      and 66 in Arm 3 being eligible. There are 112 patients (42.2%) alive with 25.3
      months of median follow-up. There were no significant baseline differences among
      groups regarding quality-of-life measures and one of the neuropsychological
      tests, namely the Hopkins Verbal Learning Test. However, at 12 months after PCI
      there was a significant increase in the occurrence of CNt in the 36-Gy cohort
      (p=0.02). Logistic regression analysis revealed increasing age to be the most
      significant predictor of CNt (p=0.005). CONCLUSIONS: Because of the increased
      risk of developing CNt in study patients with 36 Gy, a total PCI dose of 25 Gy
      remains the standard of care for patients with LD SCLC attaining a complete
      response to initial chemoradiation.

PMID- 20800382
TI  - Data-driven approach to generating achievable dose-volume histogram objectives in
      intensity-modulated radiotherapy planning.
AB  - PURPOSE: To propose a method of intensity-modulated radiotherapy (IMRT) planning
      that generates achievable dose-volume histogram (DVH) objectives using a database
      containing geometric and dosimetric information of previous patients. METHODS AND
      MATERIALS: The overlap volume histogram (OVH) is used to compare the spatial
      relationships between the organs at risk and targets of a new patient with those
      of previous patients in a database. From the OVH analysis, the DVH objectives of
      the new patient were generated from the database and used as the initial planning
      goals. In a retrospective OVH-assisted planning demonstration, 15 patients were
      randomly selected from a database containing clinical plans (CPs) of 91 previous
      head-and-neck patients treated by a three-level IMRT-simultaneous integrated
      boost technique. OVH-assisted plans (OPs) were planned in a leave-one-out manner
      by a planner who had no knowledge of CPs. Thus, DVH objectives of an OP were
      generated from a subdatabase containing the information of the other 90 patients.
      Those DVH objectives were then used as the initial planning goals in IMRT
      optimization. Planning efficiency was evaluated by the number of clicks of the
      "Start Optimization" button in the course of planning. Although the Pinnacle(3)
      treatment planning system allows planners to interactively adjust the DVH
      parameters during optimization, planners in our institution have never used this
      function in planning. RESULTS: The average clicks required for completing the CP
      and OP was 27.6 and 1.9, respectively (p <.00001); three OPs were finished within
      a single click. Ten more patient's cord + 4 mm reached the sparing goal D(0.1cc)
      <44 Gy (p <.0001), where D(0.1cc) represents the dose corresponding to 0.1 cc.
      For planning target volume uniformity, conformity, and other organ at risk
      sparing, the OPs were at least comparable with the CPs. Additionally, the
      averages of D(0.1cc) to the cord + 4 mm decreased by 6.9 Gy (p <.0001); averages
      of D(0.1cc) to the brainstem decreased by 7.7 Gy (p <.005). The averages of V(30
      Gy) to the contralateral parotid decreased by 8.7% (p <.0001), where V(30 Gy)
      represents the percentage volume corresponding to 30 Gy. CONCLUSION: The method
      heralds the possibility of automated IMRT planning.

PMID- 20800381
TI  - Mometasone furoate effect on acute skin toxicity in breast cancer patients
      receiving radiotherapy: a phase III double-blind, randomized trial from the North
      Central Cancer Treatment Group N06C4.
AB  - PURPOSE: A two-arm, double-blind, randomized trial was performed to evaluate the
      effect of 0.1% mometasone furoate (MMF) on acute skin-related toxicity in
      patients undergoing breast or chest wall radiotherapy. METHODS AND MATERIALS:
      Patients with ductal carcinoma in situ or invasive breast carcinoma who were
      undergoing external beam radiotherapy to the breast or chest wall were randomly
      assigned to apply 0.1% MMF or placebo cream daily. The primary study endpoint was
      the provider-assessed maximal grade of Common Terminology Criteria for Adverse
      Events, version 3.0, radiation dermatitis. The secondary endpoints included
      provider-assessed Common Terminology Criteria for Adverse Events Grade 3 or
      greater radiation dermatitis and adverse event monitoring. The patient-reported
      outcome measures included the Skindex-16, the Skin Toxicity Assessment Tool, a
      Symptom Experience Diary, and a quality-of-life self-assessment. An assessment
      was performed at baseline, weekly during radiotherapy, and for 2 weeks after
      radiotherapy. RESULTS: A total of 176 patients were enrolled between September
      21, 2007, and December 7, 2007. The provider-assessed primary endpoint showed no
      difference in the mean maximum grade of radiation dermatitis by treatment arm
      (1.2 for MMF vs. 1.3 for placebo; p = .18). Common Terminology Criteria for
      Adverse Events toxicity was greater in the placebo group (p = .04), primarily
      from pruritus. For the patient-reported outcome measures, the maximum Skindex-16
      score for the MMF group showed less itching (p = .008), less irritation (p =
      .01), less symptom persistence or recurrence (p = .02), and less annoyance with
      skin problems (p = .04). The group's maximal Skin Toxicity Assessment Tool score
      showed less burning sensation (p = .02) and less itching (p = .002). CONCLUSION:
      Patients receiving daily MMF during radiotherapy might experience reduced acute
      skin toxicity compared with patients receiving placebo.

PMID- 20800383
TI  - Predicted risk of radiation-induced cancers after involved field and involved
      node radiotherapy with or without intensity modulation for early-stage hodgkin
      lymphoma in female patients.
AB  - PURPOSE: To assess the excess relative risk (ERR) of radiation-induced cancers
      (RIC) in female patients with Hodgkin lymphoma (HL) female patients treated with
      conformal (3DCRT), intensity modulated (IMRT), or volumetric modulated arc (RA)
      radiation therapy. METHODS AND MATERIALS: Plans for 10 early-stage HL female
      patients were computed for 3DCRT, IMRT, and RA with involved field RT (IFRT) and
      involvednode RT (INRT) radiation fields. Organs at risk dose--volume histograms
      were computed and inter-compared for IFRT vs. INRT and 3DCRT vs. IMRT/RA,
      respectively. The ERR for cancer induction in breasts, lungs, and thyroid was
      estimated using both linear and nonlinear models. RESULTS: The mean estimated ERR
      for breast, lung, and thyroid were significantly lower (p < 0.01) with INRT than
      with IFRT planning, regardless of the radiation delivery technique used, assuming
      a linear dose-risk relationship. We found that using the nonlinear model, the
      mean ERR values were significantly (p < 0.01) increased with IMRT or RA compared
      to those with 3DCRT planning for the breast, lung, and thyroid, using an IFRT
      paradigm. After INRT planning, IMRT or RA increased the risk of RIC for lung and
      thyroid only. CONCLUSIONS: In this comparative planning study, using a nonlinear
      dose--risk model, IMRT or RA increased the estimated risk of RIC for breast,
      lung, and thyroid for HL female patients. This study also suggests that INRT
      planning, compared to IFRT planning, may reduce the ERR of RIC when risk is
      predicted using a linear model. Observing the opposite effect, with a nonlinear
      model, however, questions the validity of these biologically parameterized
      models.

PMID- 20800384
TI  - Determination of the absorbed dose rate to water for the 18-mm helmet of a gamma
      knife.
AB  - PURPOSE: To measure the absorbed dose rate to water of (60)Co gamma rays of a
      Gamma Knife Model C using water-filled phantoms (WFP). METHODS AND MATERIALS:
      Spherical WFP with an equivalent water depth of 5, 7, 8, and 9 cm were
      constructed. The dose rates at the center of an 18-mm helmet were measured in an
      8-cm WFP (WFP-3) and two plastic phantoms. Two independent measurement systems
      were used: one was calibrated to an air kerma (Set I) and the other was
      calibrated to the absorbed dose to water (Set II). The dose rates of WFP-3 and
      the plastic phantoms were converted to dose rates for an 8-cm water depth using
      the attenuation coefficient and the equivalent water depths. RESULTS: The dose
      rate measured at the center of WFP-3 using Set II was 2.2% and 1.0% higher than
      dose rates measured at the center of the two plastic phantoms. The measured
      effective attenuation coefficient of Gamma Knife photon beam in WFPs was 0.0621
      cm(-1). After attenuation correction, the difference between the dose rate at an
      8-cm water depth measured in WFP-3 and dose rates in the plastic phantoms was
      smaller than the uncertainty of the measurements. CONCLUSIONS: Systematic errors
      related to the characteristics of the phantom materials in the dose rate
      measurement of a Gamma Knife need to be corrected for. Correction of the dose
      rate using an equivalent water depth and attenuation provided results that were
      more consistent.

PMID- 20800385
TI  - Intrafractional target motions and uncertainties of treatment setup reference
      systems in accelerated partial breast irradiation.
AB  - PURPOSE: This study investigated the magnitude of intrafractional motion and
      level of accuracy of various setup strategies in accelerated partial breast
      irradiation (APBI) using three-dimensional conformal external beam radiotherapy.
      METHODS AND MATERIALS: At lumpectomy, gold fiducial markers were strategically
      sutured to the surrounding walls of the cavity. Weekly fluoroscopy imaging was
      conducted at treatment to investigate the respiration-induced target motions.
      Daily pre- and post-RT kV imaging was performed, and images were matched to
      digitally reconstructed radiographs based on bony anatomy and fiducial markers,
      respectively, to determine the intrafractional motion magnitudes over the course
      of treatment. The positioning differences of the laser tattoo- and the bony
      anatomy-based setups compared with those of the marker-based setup (benchmark)
      were also determined. The study included 21 patients. RESULTS: Although lung
      exhibited significant motion, the average marker motion amplitude on the
      fluoroscopic image was about 1 mm. Over a typical treatment time period, average
      intrafractional motion magnitude was 4.2 mm and 2.6 mm based on the marker and
      bony anatomy matching, respectively. The bony anatomy- and laser tattoo-based
      interfractional setup errors, with respect to the fiducial marker-based setup,
      were 7.1 and 9.0 mm, respectively. CONCLUSIONS: Respiration has limited effects
      on the target motion during APBI. Bony anatomy-based treatment setup improves the
      accuracy relative to that of the laser tattoo-based setup approach. Since
      fiducial markers are sutured directly to the surgical cavity, the marker-based
      approach can further improve the interfractional setup accuracy. On average, a
      seroma cavity exhibits intrafractional motion of more than 4 mm, a magnitude that
      is larger than that which is otherwise derived based on bony anatomy matching. A
      seroma-specific marker-based approach has the potential to improve treatment
      accuracy by taking the true inter- and intrafractional motions into
      consideration.

PMID- 20800386
TI  - Single-dose versus fractionated stereotactic radiotherapy for brain metastases.
AB  - PURPOSE: To evaluate the efficacy of stereotactic radiotherapy in patients with
      brain metastases by comparing two different treatment regimens, single-dose
      radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT). METHODS AND
      MATERIALS: Between November 2003 and December 2008, 98 patients with brain
      metastases were included. Fifty-eight patients were treated with SRS, and forty
      were treated with FSRT. Fractionated stereotactic radiotherapy was used for large
      lesions or lesions located near critical structures. The median doses were 20 Gy
      for the SRS group and 36 Gy in 6 fractions for the FSRT group. RESULTS: With a
      median follow-up period of 7 months, the median survival was 7 months for all
      patients, with a median of 6 months for the SRS group and 8 months for the FSRT
      group (p = 0.89). Local progression-free survival (LPFS) rates at 6 months and 1
      year were 81% and 71%, respectively, for the SRS group and 97% and 69%,
      respectively, for the FSRT group (p = 0.31). Despite the fact that FSRT was used
      for large lesions and lesions in adverse locations, LPFS was not inferior to SRS.
      Toxicity was more frequently observed in the SRS group than in the FSRT group
      (17% vs. 5%, p = 0.05). CONCLUSIONS: Because patients treated with FSRT exhibited
      similar survival times and LPFS rates with a lower risk of toxicity in comparison
      to those treated with SRS, despite the fact that FSRT was used for large lesions
      and lesions in adverse locations, we find that FSRT can particularly be
      beneficial for patients with large lesions or lesions located near critical
      structures. Further investigation is warranted to determine the optimal
      dose/fractionation.

PMID- 20800388
TI  - Three or four fractions of 4-5 Gy per week in postoperative high-dose-rate
      brachytherapy for endometrial carcinoma.
AB  - PURPOSE: To evaluate the results of high-dose-rate brachytherapy (HDRBT) using a
      schedule of three or four fractions per week, when possible, in 89 patients on
      local control and toxicity in postoperative treatment of endometrial carcinoma.
      The effect of the overall HDRBT treatment time (OTT) on toxicity was also
      evaluated. PATIENTS AND METHODS: Federation Internationale de Gynecologie
      Obstetrique Stage: 24 IB, 45 IC, 4 IIA, 6 IIB, 4 IIIA, 2 IIIB, and 4 IIIC.
      Radiotherapy: Group 1-67 of 89 patients received external beam irradiation (EBI;
      44-50 Gy) plus HDRBT (3 fractions of 4-6 Gy); Group 2-22 of 89 patients received
      HDRBT alone (6 fractions of 4-5 Gy). OTT: Group 1-HDRBT was completed in a median
      of 5 days in 32 patients and in >5 days in 35; Group 2-HDRBT was completed in <15
      days in 11 patients and in >=16 days in 11. Toxicity was evaluated using
      Radiation Therapy Oncology Group scores and the bioequivalent dose (BED) study
      was performed in vaginal mucosa surface. Statistics included Student's t test,
      chi-square test, and receiving operator curves. RESULTS: With a mean follow-up of
      31 months (range, 6-70), 1 of 89 patients had vaginal relapse. Early toxicity
      appeared in 8 of 89 (9%) patients and was resolved. Late toxicity appeared in
      13/89 (14%): vaginal nine Grade 1, three Grade 2, one Grade 4; bladder two Grade
      2; rectal three Grade 1, one Grade 2. No differences were found in relation to
      OTT in Groups 1 and 2. Mean BED was 88.48 Gy in Group 1 and 165.28 Gy in Group 2.
      Cases with Grade 2 late vaginal toxicity received >75 Gy after EBI and >165 Gy in
      Group 2. CONCLUSIONS: Three fractions of 4-5 Gy in 3-5 days after EBI or 6
      fractions in <15 days in patients receiving HDRBT alone was a safe treatment in
      relation to toxicity and local control. Vaginal surface BED less than 75 Gy after
      EBI and less than 160 Gy in HDRBT alone may be safe to avoid G2 toxicity.

PMID- 20800387
TI  - CHOD/BVAM chemotherapy and whole-brain radiotherapy for newly diagnosed primary
      central nervous system lymphoma.
AB  - PURPOSE: To assess the efficacy and toxicity of chemotherapy consisting of
      cyclophosphamide, doxorubicin (Adriamycin), vincristine, and dexamethasone (CHOD)
      plus bis-chloronitrosourea (BCNU), cytosine arabinoside, and methotrexate (BVAM)
      followed by whole-brain irradiation (WBRT) for patients with primary central
      nervous system lymphoma (PCNSL). METHODS AND MATERIALS: Patients 70 years old and
      younger with newly diagnosed, biopsy-proven PCNSL received one cycle of CHOD
      followed by two cycles of BVAM. Patients then received WBRT, 30.6 Gy, if a
      complete response was evoked, or 50.4 Gy if the response was less than complete;
      both doses were given in 1.8-Gy daily fractions. The primary efficacy endpoint
      was 1-year survival. RESULTS: Thirty-six patients (19 men, 17 women) enrolled
      between 1995 and 2000. Median age was 60.5 years (range, 34 to 69 years). Thirty
      (83%) patients had baseline Eastern Cooperative Oncology Group performance scores
      of 0 to 1. All 36 patients were eligible for survival and response evaluations.
      Median time to progression was 12.3 months, and median survival was 18.5 months.
      The percentages of patients alive at 1, 2, and 3 years were 64%, 36%, and 33%,
      respectively. The best response was complete response in 10 patients and
      immediate progression in 7 patients. Ten (28%) patients had at least one grade 3
      or higher neurologic toxicity. CONCLUSIONS: This regimen did improve the survival
      of PCNSL patients but also caused substantial toxicity. The improvement in
      survival is less than that reported with high-dose methotrexate-based therapies.

PMID- 20800389
TI  - Patterns of response after preoperative intensity-modulated radiation therapy and
      capecitabine/oxaliplatin in rectal cancer: is there still a place for
      ecoendoscopic ultrasound?
AB  - PURPOSE: The main goals of preoperative chemoradiotherapy (CHRT) in rectal cancer
      are to achieve pathological response and to ensure tumor control with functional
      surgery when possible. Assessment of the concordance between clinical and
      pathological responses is necessary to make decisions regarding alternative
      conservative procedures. The present study evaluates the patterns of response
      after a preoperative CHRT regimen, and the value of endoscopic ultrasound (EUS)
      in assessing response. METHODS AND MATERIALS: A total of 51 EUS-staged T3 to T4
      and/or N0 to N+ rectal cancer patients received preoperative CHRT (intensity
      modulated radiation therapy and capecitabine/oxaliplatin (XELOX) followed by
      radical resection. Clinical response was assesed by EUS. Rates of pathological
      tumor regression grade (TRG) and lymph node (LN) involvement were determined in
      the surgical specimen. Clinical and pathological responses were compared, and the
      accuracy of EUS in assessing response was calculated. RESULTS: Twenty-four
      patients (45%) achieved a major pathological response (complete or >95%
      pathological response (TRG 3+/4)). Sensitivity, specificity, negative predictive
      value, and positive predictive value of EUS in predicting pathological T response
      after preoperative CHRT were 77.8%, 37.5%, 60%, and 58%, respectively. The EUS
      sensitivity, specificity, negative predictive value, and positive predictive
      value for nodal staging were 44%, 88%, 88%, and 44%, respectively. Furthermore,
      EUS after CHRT accurately predicted the absence of LN involvement in 7 of 7
      patients (100%) with major pathological response of the primary tumor.
      CONCLUSION: Preoperative IMRT with concomitant XELOX induces favorable rates of
      major pathological response. EUS has a limited ability to predict primary tumor
      response after preoperative CHRT, but it is useful for accurately determining LN
      status. EUS may have a potential value in identifying patients with a very low
      risk of LN involvement in association with a good pathological response as
      potential candidates for conservative local surgical protocols.

PMID- 20800390
TI  - Comparison of nodal risk formula and MR lymphography for predicting lymph node
      involvement in prostate cancer.
AB  - PURPOSE: To compare the nodal risk formula (NRF) as a predictor for lymph node
      (LN) metastasis in patients with prostate cancer with magnetic resonance
      lymphography (MRL) using Ultrasmall Super-Paramagnetic particles of Iron Oxide
      (USPIO) and with histology as gold standard. METHODS AND MATERIALS: Logistic
      regression analysis was performed with the results of histopathological
      evaluation of the LN as dependent variable and the nodal risk according to the
      NRF and the result of MRL as independent input variables. Receiver operating
      characteristic (ROC) analysis was performed to assess the performance of the
      models. RESULTS: The analysis included 375 patients. In the single-predictor
      regression models, the NRF and MRL results were both significantly (p<0.001)
      predictive of the presence of LN metastasis. In the models with both predictors
      included, NRF was nonsignificant (p=0.126), but MRL remained significant
      (p<0.001). For NRF, sensitivity was 0.79 and specificity was 0.38; for MRL,
      sensitivity was 0.82 and specificity was 0.93. After a negative MRL result, the
      probability of LN metastasis is 4% regardless of the NRF result. After a positive
      MRL, the probability of having LN metastasis is 68%. CONCLUSIONS: MRL is a better
      predictor of the presence of LN metastasis than NRF. Using only the NRF can lead
      to a significant overtreatment on the pelvic LN by radiation therapy. When the
      MRL result is available, the NRF is no longer of added value.

PMID- 20800391
TI  - Smoking and everyday prospective memory: a comparison of self-report and
      objective methodologies.
AB  - AIMS: To examine whether persistent smoking leads to impairments in self-reported
      and objective measures of prospective memory (PM: the cognitive ability to
      remember to carry out activities at some future point in time). METHODS: An
      opportunity sample of 18 existing smokers and 22 who had never smoked were
      compared. An existing-groups design was utilised, comparing a smoking group with
      a never-smoked control group as the independent factor. Scores on the sub-scales
      of the Prospective and Retrospective Memory Questionnaire (PRMQ) and scores on
      the Cambridge Prospective Memory Test (CAMPROMPT) constituted the dependent
      factors. Age, mood, other drug use, strategy scores and IQ were also measured.
      Each participant was tested in a laboratory setting. Self-reported PM lapses were
      measured using the PRMQ. The CAMPROMPT was used as an objective measure of PM.
      Alcohol and other drug use were assessed by a Recreational Drug Use
      Questionnaire. The Hospital Anxiety and Depression Scale gauged levels of anxiety
      and depression. A strategy scale measured the number of strategies used to aid
      memory. The National Adult Reading Test measured IQ. RESULTS: After observing no
      between-group differences on age, mood, alcohol use, strategy use, and IQ,
      smokers and the never-smoked did not differ on the self-reported lapses measured
      on the PRMQ. However, smokers recalled significantly fewer items on the CAMPROMPT
      than the never-smoked group. CONCLUSION: The results of the present study suggest
      that persistent smoking leads to impairments in everyday PM.

PMID- 20800392
TI  - Predicting neurosensory disabilities at two years of age in a national cohort of
      extremely premature infants.
AB  - BACKGROUND: Extreme prematurity carries a high risk of neurosensory disability.
      AIMS: Examine which information obtained pre-, peri- and postnatally may be
      predictive of neurosensory disabilities at 2 years of age. STUDY DESIGN:
      Prospective observational study of all infants born in Norway in 1999 and 2000
      with gestational age (GA) 22-27 completed weeks or birth weight (BW) of 500-999
      g. OUTCOME MEASURES: Incidence of neurosensory disabilities. RESULTS: Of 373
      surviving children, 30 (8%) had major neurosensory disabilities (26 CP, 6 blind,
      3 deaf), and a further 46 (12%) had minor visual or hearing disabilities. The
      rate of major neurosensory disabilities was 19 of 99 (19%) for children with GA
      23-25 vs. 8 of 189 (4%) for GA 26-27 weeks (p<0.001). In a multivariable model,
      only morbidities detected in the neonatal intensive care unit (NICU) were
      associated with major neurosensory disabilities; adjusted odds ratios (95%
      confidence intervals) were 68.6 (18.7, 252.2) for major abnormalities on cerebral
      ultrasound, 6.8 (1.7, 27.4) for retinopathy of prematurity (ROP) grade>2, 3.2
      (1.0, 9.7) for ROP grade 1-2, 6.5 (1.9, 22.3) for prolonged use (> or = 21 days)
      of steroid treatment for lung disease and 3.1 (1.0, 9.4) for clinical
      chorioamnionitis. The visual outcome was strongly related to the degree of ROP
      (p<0.001), and all who had a normal hearing screen in the NICU had normal hearing
      at 2 years. CONCLUSION: NICU morbidities, rather than GA or intrauterine growth
      are the significant predictors of major neurosensory disabilities among extreme
      prematurity surviving to discharge from the NICU.

PMID- 20800393
TI  - Goat and sheep ovarian tissue cryopreservation: Effects on the morphology and
      development of primordial follicles and density of stromal cell.
AB  - The effect of exposure to cryoprotectant and cryopreservation of goat and sheep
      ovarian cortical fragments on the morphology of primordial follicles, stromal
      cell density and follicular development was performed. Goat and sheep ovarian
      fragments were exposed to 1.0 or 1.5M ethylene glycol (EG) for 5, 10 or 20min,
      followed or not by conventional cryopreservation. Follicular morphology and
      stromal cell density were evaluated by means of classical histological analysis.
      In addition, ovarian fragments were cultured for 1 or 7 days after
      cryopreservation to evaluate follicular development. Both exposure to
      cryoprotectant and cryopreservation of goat and sheep ovarian tissue did affect
      the morphology of primordial follicles and stromal cell density, except when goat
      ovarian tissue was exposed to EG for 5min. Although exposure time did not
      influence follicular morphology in both species, increase in the exposure time
      from 5 to 20min did reduce goat stromal cell density. Increase in EG
      concentration from 1.0 to 1.5M did result in the decrease of the percentage of
      goat morphologically normal primordial follicles evaluated after exposure only.
      In vitro culture of frozen-thawed goat and sheep ovarian tissue showed that
      exposure to 1.0M, for 10min, before freezing of goat and sheep ovarian tissue
      does not impair follicular developmental capacity. In addition, stromal cell
      density may play a role in follicular survival and development after
      cryopreservation of ovarian tissue.

PMID- 20800394
TI  - Vascular endothelial growth factor isoforms 120, 164 and 205 are reduced with
      atresia in ovarian follicles of sheep.
AB  - Vascular endothelial growth factor (VEGF) is a potent stimulator of endothelial
      cell proliferation and neo-vasculogenesis. In the ovary, VEGF mRNA is localised
      in the follicle, and it is associated with follicular growth and dominance.
      Alternative splicing of VEGF mRNA produces eight mature forms of mRNA for equal
      number of VEGF isoforms. In the present study, the VEGF isoforms in granulosa and
      theca cells of large (4-6mm) and preovulatory (>6mm) sheep follicles were studied
      during the process of atresia. Follicles were classified as healthy, early
      atretic and atretic, and the granulosa and theca cells were isolated. The mRNA
      for three of these isoforms was found in both theca and granulosa cells, and was
      quantified by image analysis after RT-PCR using primers that amplified VEGF120,
      VEGF164, VEGF188 and VEGF205 isoforms. The mRNA for these three isoforms was
      found in both theca and granulosa cells of healthy and atretic follicles. Atresia
      was accompanied with a reduction in mRNA for VEGF164 and VEGF120 in granulosa and
      theca cells (P<0.05). Amounts of both isoforms were reduced with the extent of
      atresia in the granulosa cells, whilst in the theca cells this reduction was only
      evident in advanced atretic follicles. Furthermore, after the onset of atresia,
      VEGF205 was not detectable in the granulosa cells. Follicle size did not affect
      the amount of VEGF mRNA. Hence, the onset of atresia in follicles of sheep is
      coupled with a reduction in VEGF mRNA. The decrease in VEGF observed with atresia
      in follicles of sheep was greater in granulosa than in theca cells.

PMID- 20800395
TI  - Determination of the sequence of latent fingermarks and writing or printing on
      white office paper.
AB  - Latent fingermarks were deposited onto white office paper samples containing
      writing or printing from several media (for example, ballpoint pens and laser
      printers). Fingermarks were deposited both before and after writing/printing. The
      marks were then treated with appropriate latent fingermark development
      techniques. Once treated, they were examined with standard techniques applied in
      document examination (filtered light analysis, electrostatic detection device and
      Raman spectroscopy) to determine the sequence of application. The results
      suggested that the sequence of laser printing and latent marks could be
      determined via electrostatic detection device examination of undeveloped and
      Ninhydrin developed samples.

PMID- 20800396
TI  - Four cases of acute epiglottitis with a peritonsillar abscess.
AB  - We report four cases of acute epiglottitis with a peritonsillar abscess
      originating from the inferior pole of the palatine tonsil. All cases were male,
      and presented with acute onset of sore throat and dysphagia. Flexible
      laryngoscopy revealed swollen epiglottis and swelling at the base of tongue along
      the edge of the epiglottis in all cases. Computed tomography (CT) revealed the
      position and extent of a peritonsillar abscess. Surgical drainage was not
      performed. Abscesses decreased in size following intravenous antibiotics and
      corticosteroids. We surmise that inflammatory exudates extending widely in the
      pre-epiglottic space cause epiglottic swelling from oropharyngeal infection, the
      latter of which is thought to produce a peritonsillar abscess. We recommend CT
      examination for patients with a stable airway and swollen epiglottis, even if the
      swelling is mild. This will allow for exclusion of deep neck abscess and
      determination of the most effective treatment including intravenous antibiotics
      against anaerobe, incision and drainage of an abscess.

PMID- 20800397
TI  - [Clones of Neisseria meningitidis strains in Mali].
AB  - OBJECTIVE: The purpose of our study was to identify strains of Neisseria
      meningitidis isolated from 2005 to 2007 in Mali. PATIENTS AND METHOD: We carried
      out a cross-sectional and descriptive study of 1573 meningitidis suspected case
      cerebrospinal fluid (CSF) samples before antibiotherapy. The identification of
      isolated germs was serogroup, serotype, subtype, sequence type, and clonal
      complexes. RESULTS: CSF samples were taken from children under 1 (30.1%),
      children between 1 and 4 (26.3%), and children between 5 and 14 years of age
      (25.7%). Neisseria meningitidis was identified in 144 out of 244 CSF positive
      samples. Streptococcus pneumoniae (73/244), and Haemophilus influenzae b (44/244)
      were also present. The most frequent Neisseria meningitidis serogroups were A,
      W135, and Y. Genotyping of the 33 live Neisseria meningitidis strains showed that
      three clonal complexes were present, especially serogroup A complex ST-5 with
      sequence type ST-7 and ST-2859, serogroup W135 complex ST-11 with sequence type
      ST-11, and serogroup Y complex ST-167 with sequence type ST-167 and ST-192.
      DISCUSSION: The introduction of tetravalent vaccine ACYW135 should be considered
      in Mali and West Africa.

PMID- 20800398
TI  - [Post-malaria neurological syndrome complicating a relapse of Plasmodium
      falciparum malaria after atovaquone-proguanil treatment].

PMID- 20800399
TI  - Synthetic lethal interaction may be a new approach in chemoprevention of
      colorectal cancer.

PMID- 20800400
TI  - Is Reynolds syndrome a genetic laminopathy?
AB  - Reynolds syndrome is a rare disease associating primary biliary cirrhosis (PBC)
      and systemic scleroderma (SSc). Although generally considered as an autoimmune
      disease owing to the presence of typical autoantibodies and to microscopical
      abnormalities suggesting autoimmunity (lymphoid infiltrate around the biliary
      ducts and the cutaneous vessels, pericarditis, pleurisy), other causes have been
      searched for, especially genetic. The discovery of a new mutation in the Lamin
      receptor B in a French patient suffering from Reynolds syndrome [1] revives this
      controversy. Laminopathies have a great variety of manifestations, but some are
      quite comparable with either SSc or PBC, and the new mutation has been found
      neither in a group of 27 other patients with SSc, nor in 400 normal subjects.
      After bioinformatics searching, the authors claim that it is plausible that the
      new mutation is pathogenic. It remains to be shown, however, that this is really
      the case by testing directly the liver and skin fibroblasts of the patient.
      Moreover, looking at a series of CBP patients and at a larger SSc sample will be
      enlightening to appreciate the real value of that discovery.

PMID- 20800401
TI  - PET/CT with 68Gallium-DOTA-peptides in NET: an overview.
AB  - In the present review article we presented the major technical innovations
      regarding the diagnosis of NET with PET/CT 68Ga-DOTA-peptides compounds over
      conventional radiologic and scintigraphic imaging, discussing both the different
      types of radiopharmaceuticals commercially available, trying to making a
      comparison on the possible advantages and drawbacks of these
      radiopharmaceuticals, and providing also some technical recommendations to the
      radiologists and nuclear physicians for using these new methodology in an
      appropriate manner in the clinical setting.

PMID- 20800402
TI  - Ultrasound characterization of the seminal vesicles in infertile patients with
      type 2 diabetes mellitus.
AB  - Male patients with type 2 diabetes mellitus (DM) may experience infertility
      because the disease affects negatively many aspects of reproduction, including
      seminal vesicle (SV) function. The aim of this study was to evaluate the
      ultrasound characteristics of the SVs of infertile patients with DM because no
      such data are available in these patients. To accomplish this, 25 infertile
      patients with type 2 DM and no other known causes of sperm parameter
      abnormalities were selected. Two different control groups were also enrolled:
      healthy men with idiopathic infertility (n=25) and infertile patients with male
      accessory gland infections (MAGI) (n=25), a well-studied clinical model of SV
      inflammation. Patients and controls underwent prostate-vesicular transrectal
      ultrasonography after 1 day of sexual abstinence before and 1h after ejaculation.
      The following SV ultrasound parameters were recorded: (1) body antero-posterior
      diameter (ADP); (2) fundus APD; (3) parietal thickness of the right and left SVs;
      (4) number of polycyclic areas within both SVs; (5) fundus/body ratio; (6)
      difference of the parietal thickness between the right and the left SV; and (7)
      pre- and post-ejaculatory APD difference. Patients with DM had a significantly
      (p<0.05) higher F/B ratio compared to controls and patients with MAGI. Only
      patients with MAGI had a significantly (p<0.05) higher number of polycyclic
      areas. Controls and MAGI patients have a similar pre- and post-ejaculatory
      difference of the body SV APD, whereas this difference was significantly (p<0.05)
      lower in patients with DM. In conclusion, this study showed that infertile
      patients with DM have peculiar SV ultrasound features suggestive of functional
      atony.

PMID- 20800403
TI  - Effectiveness of the STIR turbo spin-echo sequence MR imaging in evaluation of
      lymphadenopathy in esophageal cancer.
AB  - PURPOSE: We have investigated the utility of the STIR TSE sequence in the
      differentiation of benign from malignant mediastinal lymph nodes in patients with
      esophageal cancer. PATIENTS AND METHODS: This study included 35 consecutive
      patients who were diagnosed as esophageal cancer and were undergone surgery. STIR
      TSE sequences were obtained as the ECG trigger. The signal intensity of the
      benign and malign lymph nodes, normal esophagus, and pathologic esophagus can be
      calculated on STIR sequence. RESULTS: Pathologically, the number of total lymph
      nodes in 35 operated cases was 482. Approximately 152 lymph nodes were detected
      with MR imaging. Of these, 28 were thought to be malignant, and 124 were thought
      to be benign, although 32 were malignant and 120 were benign according
      pathological results. The ratio of benign lymph node intensity value to normal
      esophagus intensity value was 0.73+/-0.3. The ratio of malignant lymph node
      intensity value to normal esophagus intensity value ratio was 2.03+/-0.4.
      According to these results, the sensitivity of MR was 81.3%, the specificity was
      98.3%. CONCLUSION: We think that if motionless images can be obtained with MRI,
      we may be able to differentiate benign lymph nodes from malignant ones.

PMID- 20800404
TI  - Choline PET/CT for prostate cancer: main clinical applications.
AB  - Several studies investigated the potential roles of imaging modalities in
      prostate cancer patients for the evaluation of intra-prostatic disease, stage and
      restage. However no precise guidelines exist about the use of imaging modalities,
      in particular about the role of PET/CT hybrid imaging. Considering the results of
      the literature and our experience, we tried to summarize the main applications of
      choline positron emission tomography (PET) in prostate cancer patients. The use
      of choline PET/CT for initial diagnosis and staging is not recommended as a first
      line method. Instead the main and important application of choline PET/CT is
      represented by the restaging of the disease in case of biochemical relapse for
      the detection of lymph node and distant recurrence. In particular choline PET/CT
      could play a crucial role as first diagnostic procedure in prostate cancer
      patients who show a fast growing Prostate Specific Antigen (PSA) kinetics.

PMID- 20800405
TI  - Non-enhanced MR angiography of renal artery using inflow-sensitive inversion
      recovery pulse sequence: a prospective comparison with enhanced CT angiography.
AB  - PURPOSE: To prospectively evaluate the diagnostic value of non-enhanced inflow
      sensitive inversion recovery (IFIR) MR angiography for the detection of renal
      artery stenosis (RAS), with enhanced CT angiography performed as the reference
      standard. MATERIALS AND METHODS: Sixty consecutive patients suspected of RAS
      underwent both of IFIR MR and enhanced CT angiography. Subjective image quality,
      renal artery depiction and renal artery grading were all evaluated on artery-by
      artery basis. Spearman rank correlation analysis was used to assess agreement
      between the two techniques. The diagnostic sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV) for RAS detection at
      IFIR MR angiography were calculated. RESULTS: One hundred twenty-six main renal
      arteries were visualized on enhanced CT and non-enhanced MR angiographic images,
      respectively. The Spearman rank correlation was 0.773 (P<.001) for renal artery
      depiction, 0.998 (P<.001) for renal arteries grading and 0.833 (P<.001) for RAS
      detection between the two modalities. The sensitivity, specificity, PPV and NPV
      of IFIR MR angiography for RAS detection demonstrated 100%, 99.0%, 92.0% and
      100%, respectively. CONCLUSION: Non-enhanced IFIR MR angiography had high
      sensitivity, specificity, PPV and NPV for RAS detection. It could be the first
      choice of renal artery imaging methods to avoid ionizing irradiation and renal
      toxicity from contrast media.

PMID- 20800406
TI  - Assessment of the quality and structural integrity of a complex glycoprotein
      mixture following extraction from the formulated biopharmaceutical drug product.
AB  - Biological drugs represent an important and rapidly growing class of therapeutics
      useful in the treatment of a variety of disorders ranging from cancer to
      inflammation to infectious diseases. Unlike single chemical entities, the
      recombinant production of these drugs in living cells confers considerable
      structural and chemical heterogeneity to the biologically derived protein product
      that constitutes the active pharmaceutical ingredient (API). In mammalian based
      expression systems, much of this diversity is conferred through heterogeneous
      protein glycosylation. These post-translational modifications can have
      significant effects on the structure, biological function, and pharmacological
      properties of the API. In addition, the bulk proteins that comprise the API are
      further formulated through the use of multiple excipients designed to ensure
      product stability, solubility, and lot-to-lot consistency. Unfortunately, these
      matrices can interfere with commonly available analytical methods used in the
      thorough chemical characterization of the biological drug product. At the same
      time, a demonstration of the suitable extraction of the bulk drug substance in a
      manner and form that does not destabilize the active ingredient or introduce any
      structural bias with direct reference to the original drug product is both
      critical and necessary. Here, we use recombinant human follicle stimulating
      hormone (follitropin alpha for injection) from a pharmaceutical source as an
      example to illustrate a suitable purification strategy to effectively extract the
      bulk drug substance from the formulated drug product with high purity and yield.
      We assess the suitability of this extraction method in preserving the structural
      integrity and overall quality of the drug substance relative to the formulated
      drug product, placing a particular emphasis on glycosylation as a key product
      attribute. In so doing, we demonstrate that it is possible to effectively extract
      the active pharmaceutical ingredient from a formulated biological drug product in
      a manner that is consequently sufficient for its use in comparability studies.

PMID- 20800408
TI  - Female with abdominal pain and neck swelling.

PMID- 20800407
TI  - New P2Y12 inhibitors versus clopidogrel in percutaneous coronary intervention: a
      meta-analysis.
AB  - OBJECTIVES: The purpose of this study was to perform a meta-analysis of
      randomized trials that compare new P2Y(12) inhibitors with clopidogrel to
      determine whether they improve clinical outcomes after percutaneous intervention
      (PCI). BACKGROUND: Ticlopidine/clopidogrel prevents major adverse cardiac events
      after PCI, but no trials have shown an effect on mortality. New P2Y(12)
      inhibitors are more potent and evaluated in PCI. Whether they decrease mortality
      after PCI compared with clopidogrel is unknown. METHODS: MEDLINE and Cochrane
      Controlled Trials Register databases were searched from January 1980 through
      January 2010. Randomized, placebo-controlled trials that compared new P2Y(12)
      antagonists with clopidogrel in PCI were selected. Data from 8 studies were
      evaluated and analyses performed for all randomized patients, PCI patients (any
      PCI), and PCI for ST-segment elevation myocardial infarction (STEMI) patients.
      All-cause mortality was the primary efficacy end point. Thrombolysis In
      Myocardial Infarction major bleeding was the primary safety end point. RESULTS: A
      total of 48,599 patients were included with 94% of patients with acute coronary
      syndrome and 84% of patients undergoing PCI. New P2Y(12) inhibitors significantly
      decreased death (odds ratio [OR]: 0.83, 95% confidence interval [CI]: 0.75 to
      0.92, p < 0.001 for the whole cohort; OR: 0.85, 95% CI: 0.75 to 0.96, p = 0.008
      for any PCI; and OR: 0.78, 95% CI: 0.66 to 0.92, p = 0.003 for PCI for STEMI). In
      PCI patients, new P2Y(12) inhibitors also significantly decreased major adverse
      cardiac events by 18% (p < 0.001) and stent thrombosis by 40% (p < 0.001).
      Although there was an increase in Thrombolysis In Myocardial Infarction major
      bleeding for any PCI (OR: 1.23, 95% CI: 1.04 to 1.46, p = 0.01), no difference
      was observed in PCI for STEMI (OR: 0.98, 95% CI: 0.85 to 1.13, p = 0.76), with
      similar outcomes in primary PCI for STEMI. Results were confirmed in sensitivity
      analyses that removed the largest study. CONCLUSIONS: New P2Y(12) inhibitors
      decrease mortality after PCI compared with clopidogrel. The risk/benefit ratio is
      particularly favorable in PCI for STEMI patients.

PMID- 20800409
TI  - Successful tracheal intubation through an intubating laryngeal airway in
      pediatric patients with airway hemorrhage.
AB  - BACKGROUND: This case report describes the use of the air-Q intubating laryngeal
      airway (air-Q ILA; Cookgas LLC, St. Louis, MO) for airway rescue and a conduit
      for blind tracheal intubation in two pediatric patients with failed rapid
      sequence intubation and difficult airways secondary to airway bleeding in the
      emergency department (ED). OBJECTIVES: To describe the use of a new supraglottic
      rescue device in the management of the pediatric patient's difficult airway in
      the emergency setting. CASE REPORT: Case 1 was a 5-year-old boy who presented to
      the ED for bleeding one day after his tonsillectomy. After a rapid sequence
      intubation, direct laryngoscopy was difficult, with copious bleeding in the
      oropharynx and inability to visualize the glottis. After two failed direct
      laryngoscopic attempts to intubate, a size-2 air-Q ILA was inserted. A cuffed 5.0
      mm inner diameter (ID) endotracheal tube (ETT) was blindly inserted through the
      lumen of the air-Q ILA into the trachea successfully. Case 2 was a 13-year-old
      boy who presented to the ED with a large nasopharyngeal laceration from a motor
      vehicle accident. After a rapid sequence intubation, direct laryngoscopy showed
      copious blood with no glottic visualization. A size 3 Laryngeal Mask Airway
      ClassicTM (cLMA; LMA North America Inc., San Diego, CA) was inserted with a large
      airway leak, and blind ETT insertion via the cLMA was unsuccessful. Subsequently,
      a size-2.5 air-Q ILA was inserted and adequate ventilation was restored. A cuffed
      6.0-mm ID ETT was blindly inserted through the air-Q ILA into the trachea
      successfully. CONCLUSION: Two cases of failed laryngoscopy in pediatric patients
      with blood in the airway are described. In each case, insertion of an air-Q ILA
      was followed by successful blind tracheal intubation via the lumen of the air-Q
      ILA.

PMID- 20800410
TI  - Hypotension is uncommon in patients presenting to the emergency department with
      non-traumatic cardiac tamponade.
AB  - BACKGROUND: Cardiac tamponade is a life-threatening disease in which hypotension
      is believed to be a common finding. Prior inpatient studies have described
      normotensive or hypertensive cases of tamponade; however, because the data were
      not collected from the Emergency Department (ED), the hemodynamic spectrum may
      differ from those presenting to the ED. OBJECTIVES: We hypothesized that
      hypotension is uncommon in patients presenting to the ED with non-traumatic
      tamponade. METHODS: A retrospective chart review was conducted between January
      2002 and December 2007 of patients presenting to our ED who were subsequently
      diagnosed with cardiac tamponade. RESULTS: A total of 34 patients were identified
      with a diagnosis of tamponade. The mean blood pressure on ED arrival was 131/79mm
      Hg. Upon initial presentation to the ED, 35% (n=12) of patients were
      hypertensive, 50% (n=17) were normotensive, and 15% (n=5) were hypotensive. Of
      the 5 patients who were hypotensive on ED arrival, only 2 (6% of all patients)
      remained hypotensive upon admission to the hospital and before a
      pericardiocentesis. An average of 995mL of fluid was removed from the
      pericardium. The chief complaint for the majority of patients in tamponade was
      shortness of breath (70%); 59% were tachycardic in the ED, and 72% had
      cardiomegaly on chest X-ray study. CONCLUSIONS: Hypotension is uncommon in
      patients presenting to the ED with non-traumatic cardiac tamponade. The majority
      of patients are normotensive or even hypertensive. Thus, the emergency physician
      should not exclude the diagnosis of tamponade even in light of normotension or
      hypertension.

PMID- 20800411
TI  - Purchase and use patterns of heroin users at an inner-city emergency department.
AB  - BACKGROUND: Many consider heroin abuse a problem of the inner city, but suburban
      patients may also be at risk. OBJECTIVE: To characterize the demographics and
      purchase/use patterns of heroin users in an inner-city emergency department (ED).
      METHODS: The study was conducted in one of the most impoverished and crime-ridden
      cities in the United States. Demographics and substance use habits of ED patients
      were prospectively collected. Patients who were<18 years of age, cognitively
      impaired, or did not speak English were excluded. Participants were further
      categorized as homeless, inner-city, and suburban residents. RESULTS: Of 3947
      participants, 608 (15%) used an illicit substance in the past year, with
      marijuana (9%) and cocaine (6%) the most commonly used. Heroin ranked third, used
      by 180 (5%) participants, with 61% male, 31% black, and 20% Hispanic. There were
      64 homeless, 60 suburban, and 56 inner-city heroin users. The most common route
      of use was injection (68%), with the highest rate in the homeless (84%). The
      majority of homeless and inner-city users bought (73%, both groups) and used
      (homeless 74%, inner city 88%) in the inner city. Of suburban users, 58%
      purchased and 61% used heroin in the inner city. Prescription narcotic use was
      more common in homeless (20%) and suburban (23%) heroin users than in inner-city
      users (9%) (p<0.001). CONCLUSIONS: Heroin is the third most commonly used illicit
      substance by ED patients, and a significant amount of inner-city purchase and use
      activity is conducted by suburban heroin users.

PMID- 20800412
TI  - Bilateral mastoiditis from red tide exposure.
AB  - BACKGROUND: Bilateral mastoiditis in adults has previously been reported only in
      association with diabetes mellitus or immunocompromised patients. OBJECTIVES: To
      describe a case of bilateral mastoiditis in a healthy adult and to investigate
      the etiology. CASE REPORT: A 53-year-old woman presented to the Emergency
      Department with bilateral otitis externa and mastoiditis after scuba diving
      during a harmful algal bloom, commonly known as a "red tide." The levels of
      coliform bacteria recorded at the time and location of her dive exceeded health
      regulatory limits and correlate with her atypical culture results. CONCLUSION:
      Elevated bacterial counts that result from harmful algal blooms may account for
      this rare infection.

PMID- 20800413
TI  - Isolated capitate and hamate dislocation.

PMID- 20800415
TI  - Informed decision-making in prenatal screening for Down's syndrome: what
      knowledge is relevant?
AB  - OBJECTIVE: To determine the content of decision-relevant knowledge needed for
      informed decision-making about (non-) participation in prenatal screening for
      Down's syndrome (DS), in order to develop a knowledge questionnaire for routine
      application in large-scale programme evaluations. METHODS: A generic list of
      content domains for knowledge about screening was extracted from the literature.
      Items reflecting specific knowledge domains were constructed. An expert group of
      professionals and pregnant women expressed whether domains and items represented
      decision-relevant information. RESULTS: All presented domains were scored as
      (very) important. Options when receiving an 'increased probability for DS' test
      result, the meaning of this result, the aim of the screening, and voluntary
      nature of the test were scored as most important. The condition being screened
      for, prevalence, and the screening procedure were scored as relatively less
      important, with a high amount of expert consensus. CONCLUSION: A knowledge
      measure for prenatal screening for DS was developed, based on domains and items
      acquired by expert consensus. PRACTICE IMPLICATIONS: This measure of decision
      relevant knowledge can be used in routine, large-scale evaluations of the
      procedure for offering information about prenatal screening for DS.

PMID- 20800414
TI  - Asking questions: the effect of a brief intervention in community health centers
      on patient activation.
AB  - OBJECTIVE: To evaluate the impact of a patient activation intervention (PAI)
      focused on building question formulation skills that was delivered to patients in
      community health centers prior to their physician visit. METHODS: Level of
      patient activation and patient preferred role were examined using the patient
      activation measure (PAM) and the patient preference for control (PPC) measure.
      RESULTS: More of the 252 patients evaluated were at lower levels of activation
      (PAM levels 1 or 2) than U.S. population norms before the intervention. Paired
      samples t-test revealed a statistically significant increase from pre
      intervention to post-visit PAM scores. One-third of participants moved from lower
      levels of activation to higher levels (PAM levels 3 or 4) post-intervention.
      Patients preferring a more passive role had lower initial PAM scores and greater
      increases in their post-intervention PAM scores than did those who preferred a
      more active role. CONCLUSION: Patients exposed to the PAI demonstrated
      significant improvement on a measure of activation. The PAI may be useful in
      helping patients prepare for more effective encounters with their physicians.
      PRACTICE IMPLICATIONS: The PAI was feasible to deliver in the health center
      setting and may be a useful method for activating low-income, racial/ethnic
      minority patient populations.

PMID- 20800416
TI  - The middle-arm fistula as a valuable surgical approach in patients with end-stage
      renal disease.
AB  - BACKGROUND: American and European guidelines recommend the distal radial-cephalic
      fistula (dRCF) as the first and best hemodialysis access in patients with end
      stage renal disease (ESRD). However, this kind of arteriovenous fistula (AVF)
      shows a limited primary unassisted patency and frequently needs surgical
      revisions or angiographic procedures, or both. When dRCF is not feasible,
      guidelines suggest a proximal brachiocephalic AVF. The middle-arm fistula (MAF),
      or autogenous forearm radial-median direct access, has been suggested as a
      possible alternative approach. This study evaluated MAF primary unassisted
      patency, the most frequent causes of MAF failure, and the possible related
      factors. METHODS: Data on patients with a MAF placed from January 1991 until June
      2008 were retrospectively collected. The probability of MAF failure overall and
      by the main subgroups was estimated according to Kaplan-Meier with Greenwood
      standard error (SE). Comparison of failure among different subgroups was
      performed using the log rank test in univariate analyses. The Cox regression
      model was used to investigate factors that independently affected the overall
      hazard of failure and cause-specific hazard of thrombosis. RESULTS: At the end of
      follow-up, 14.0% of MAF failed (11.6% thrombosis, 1.7% stenosis, 0.7% failed
      maturation), and 44.2% of MAF were still working. Cumulative probability of MAF
      unassisted primary patency after 4 years from the creation was 79%. Univariate
      analyses highlighted that women (P = .019), underweight patients (P = .010), and
      MAF implantation after starting hemodialysis (P < .001) had a higher risk of MAF
      failure for any cause than men, normal and overweight patients, and MAF implanted
      before starting hemodialysis. Results of the Cox multivariate analysis for
      overall MAF failure confirmed that only MAF implantation before starting
      hemodialysis is a protective factor against any failure (P = .003), whereas
      female gender (P = .016) was associated with an increase of the thrombosis hazard
      ratio to 2.04 (95% confidence interval, 1.14-3.63). CONCLUSION: Our data
      demonstrate that MAF has a good unassisted primary patency and suggest that this
      kind of AVF could be a valuable alternative surgical approach when dRCF is not
      feasible in ESRD patients.

PMID- 20800417
TI  - Stent graft-induced new entry after endovascular repair for Stanford type B
      aortic dissection.
AB  - BACKGROUND: Stent graft-induced new entry (SINE), defined as the new tear caused
      by the stent graft and excluding those arising from natural disease progression
      or iatrogenic injury from the endovascular manipulation, has been increasingly
      observed after thoracic endovascular aortic repair (TEVAR) for Stanford type B
      dissection in our center. SINE appears to be remarkably life threatening. We
      investigated the incidence, mortality, causes, and preventions of SINE after
      TEVAR for Stanford type B dissection. METHODS: Data for 22 patients with SINE
      were retrospectively collected and analyzed from 650 patients undergoing TEVAR
      for type B dissection from August 2000 to June 2008. An additional patient was
      referred to our center 14 months after TEVAR was performed in another hospital.
      The potential associations of SINE with Marfan syndrome, location of SINE and
      endograft placement, and the oversizing rate were analyzed by Fisher exact
      probability test or t test. RESULTS: We found 24 SINE tears in 23 patients,
      including SINE at the proximal end of the endograft in 15, at the distal end in
      7, and at both ends in 1. Six patients died. SINE incidence and mortality reached
      3.4% and 26.1%, respectively. Two SINE patients were diagnosed with Marfan
      syndrome, whereas there were only 6 Marfan patients among the 651 patients. The
      16 proximal SINEs were evidenced at the greater curve of the arch and caused
      retrograde type A dissection. The eight distal SINEs occurred at the dissected
      flap, and five caused enlarging aneurysm whereas three remained stable. The
      endograft was placed across the distal aortic arch during the primary TEVAR in
      all 23 patients. The incidence of SINE was 33.33% among Marfan patients vs 3.26%
      among non-Marfan patients (P = .016). There was no significant difference in
      mortality between proximal and distal SINE (25% vs 28.6%, P > .99), incidence of
      SINE between endograft placement across the arch and at the straight portion of
      descending thoracic aorta (23 of 613 vs 0 of 38, P = .39), and the oversizing
      rate between SINE and non-SINE patients (13% +/- 4.5% vs 16% +/- 6.5%, P = .98).
      CONCLUSIONS: SINE appears not to be rare after TEVAR for type B dissection and is
      associated with substantial mortality. The stress yielded by the endograft seems
      to play a predominant role in its occurrence. It is important to take this stress
      induced injury into account during both design and placement of the endograft.

PMID- 20800418
TI  - Lymphatic malformation is a common component of Klippel-Trenaunay syndrome.
AB  - OBJECTIVES: Few previous studies have focused on the involvement of the lymphatic
      system in Klippel-Trenaunay syndrome (KTS), although some evidence suggests that
      lymphatic abnormalities are associated with the disease. The aim of the present
      study was to investigate the involvement of the lymphatic system in KTS. METHODS:
      Magnetic resonance lymphangiography (MRL) with the use of gadobenate dimeglumine
      as the contrast was performed on 32 patients with KTS involving the extremities
      to evaluate lymphatic vessels, lymph nodes, and veins. RESULTS: Thirty-one of 32
      patients exhibited lymphatic vessel and/or lymph node anomalies, including
      hyperplasia (11/31), hypoplasia or aplasia (20/31) of lymphatic vessels, and
      lymphedema (31/31) of the affected limbs. Twenty-two patients showed asymmetry of
      the inguinal nodes exhibiting either the absence, or an increase or a decrease in
      number and size of the inguinal nodes. Venous dysplasia was found in 31 patients
      in superficial and/or deep veins. The results showed a high concomitance of
      malformations of the lymphatic system and veins in the affected limbs of patients
      with KTS. CONCLUSIONS: Lymphatic system abnormalities as examined with MRL are
      commonly associated with KTS and are likely to play a significant role in the
      disorder.

PMID- 20800419
TI  - Advanced thoracic endovascular aortic repair: late complications of thoracic
      endografts.

PMID- 20800420
TI  - Traumatic thoracic aortic injury and ruptures.

PMID- 20800421
TI  - Required skills and interdisciplinary teams in starting a TEVAR practice.

PMID- 20800422
TI  - Fenestrated and branched devices in the pipeline.

PMID- 20800423
TI  - Thoracic aortic endovascular repair for mycotic aneurysms and fistulas.

PMID- 20800424
TI  - Novel aspects of in vitro IL-2 or IFN-alpha enhanced NK cytotoxicity of healthy
      individuals based on NKG2D and CD161 NK cell receptor induction.
AB  - As IL-2 and IFN-alpha modulate NK cell activity it was of interest to investigate
      the expression of newly defined NK cell receptors and augmented NK cell activity
      in healthy individuals after cytokine in vitro treatment. Peripheral blood
      lymphocytes (PBL) obtained from 31 healthy volunteers treated for 18 h with 200
      IU/ml IL-2 and 250 IU/ml IFN-alpha were evaluated for NK cell cytotoxicity.
      Expression of NKG2D, CD161, CD158a, CD158b receptors was analyzed on CD3-CD16+ NK
      cells, cytotoxic CD16(bright) and regulatory CD16(dim) subsets by FACS flow. The
      found induced significant in vitro enhancement of NK cell activity by both
      cytokines is supported by specific cytokine induction in PBL of pSTAT1 and
      pSTAT5, determined by Western blotting, as well as induction of IRF-1
      transcription. Both cytokines induce significant up-regulation of NKG2D
      expression while only IFN-alpha induced significant up-regulation of CD161, with
      no alteration in KIR expression by either cytokine on CD3-CD16+ NK cells.
      Investigated cytokines did not induce change in NK cell bright and dim subset
      distribution. Moreover, we find that, not only cytokine receptor induction on the
      CD3-CD16+ NK cells, but also simultaneous increase in their percentage and/or
      density on CD16(bright) and CD16(dim) subsets, represent good indicators of
      receptor cytokine-susceptibility. As the role of NK cells has been shown in the
      loss of tolerance, infection and cancer, the data obtained in this study may be
      of help in NK cell profiling, by giving referent values of cytokine-induced novel
      NK cell receptor expression either in evaluation of these diseases or in
      immunomonitoring during cytokine immunotherapy.

PMID- 20800425
TI  - The care strategy for families of terminally ill cancer patients who become
      unable to take nourishment orally: recommendations from a nationwide survey of
      bereaved family members' experiences.
AB  - CONTEXT: Anorexia is one of the most common symptoms in terminally ill cancer
      patients and causes considerable distress for both patients and their families.
      OBJECTIVES: The primary aims of the present study were to clarify the level of
      the family-perceived emotional distress and necessity for improvement in
      professional practice when a relative becomes unable to take nourishment orally
      and explore the determinants of these outcomes. The ultimate aim was to develop
      an effective care strategy for family members of terminally ill cancer patients
      who become unable to take nourishment orally. METHODS: A cross-sectional
      anonymous nationwide survey was conducted involving 662 bereaved family members
      of cancer patients who had been admitted to 95 palliative care units throughout
      Japan. RESULTS: A total of 452 bereaved family members returned the
      questionnaires (effective response rate, 68%). Overall, 80% of family members
      experienced the situation where a terminally ill relative became unable to take
      nourishment orally. The reported level of family-perceived emotional distress was
      very distressing (38%) and distressing (33%). Responses to the family-perceived
      necessity for improvement in professional practice they received were much
      improvement needed (4%), considerable improvement needed (10%), and some
      improvement needed (46%). The independent determinants of a high level of family
      perceived emotional distress were a sense of helplessness and guilt, and belief
      that dehydration causes profound distress for dying patients. Independent
      determinants of a high level of family-perceived necessity for improvement in
      professional practice were a sense of helplessness and guilt, experience that
      health care providers did not pay enough attention to family members' concerns,
      and insufficient relief of the patient's symptoms. CONCLUSION: A considerable
      number of family members experienced high levels of emotional distress when a
      terminally ill cancer patient became unable to take nourishment orally, and many
      perceived a necessity for improvement in professional practice they received. A
      recommended care strategy includes the following four major domains: 1) relieving
      the family members' sense of helplessness and guilt, 2) providing up-to-date
      information about hydration and nutrition at the end of life, 3) understanding
      family members' concerns and providing emotional support, and 4) relieving the
      patient's symptoms. Further research is needed to evaluate the effects of this
      care strategy on family members' outcomes, including clinical studies to obtain
      more accurate understanding of the symptomatic effects of hydration and nutrition
      in terminally ill cancer patients.

PMID- 20800426
TI  - Social anxiety and posttraumatic stress symptoms: the impact of distressing
      social events.
AB  - Recent evidence supports the notion that relatively common social events, such as
      public humiliation and teasing, may precipitate or exacerbate symptoms of social
      anxiety disorder (SAD; Erwin et al., 2006; McCabe et al., 2010). In addition,
      individuals with SAD often report event-specific hallmark symptoms of
      posttraumatic stress (PTSS; e.g., intrusive memories, avoidance, hyperarousal)
      following significant negative social events. Although intriguing, there is a
      paucity of research data to date exploring the relationships between negative
      social events, social anxiety, and PTSS. The present study (1) assessed
      endorsement rates of negative social events; (2) compared patterns of social
      anxiety and PTSS reporting among persons reporting negative social events
      relative to persons reporting the Criterion A1 events associated with
      posttraumatic stress disorder; and (3) evaluated the interrelationships between
      social anxiety and PTSS, and common constructs including fear of negative
      evaluation, anxiety sensitivity, and depression. Participants included community
      members (n = 601; 74% women; M(age) = 25.8, SD = 9.8) who endorsed experiencing a
      significantly negative social event. Approximately 55% of all participants
      reported experiencing a negative social event, with one-third of those indicating
      it was worse than the Criterion A events they had experienced. Participants
      reporting negative social events scored higher on measures of social anxiety and
      PTSS than those reporting only Criterion A events. Trauma symptoms only predicted
      social anxiety symptoms for participants who reported a negative social event.
      Comprehensive results and directions for future research are discussed.

PMID- 20800427
TI  - Hoarding among patients seeking treatment for anxiety disorders.
AB  - The aim of the present study was to examine the prevalence of hoarding symptoms
      among individuals presenting for treatment of anxiety symptoms. Participants
      included 130 adults who were seeking treatment at an outpatient anxiety disorders
      clinic between January 2004 and February 2006. During their initial assessment,
      participants (31 with panic disorder, 15 specific phobia, 27 social phobia, 36
      obsessive-compulsive disorder, 21 generalized anxiety disorder, mean age 37
      years, 57% female, 88% White) completed the Saving Inventory-Revised, a self
      report measure of hoarding symptoms, and several measures of anxiety symptoms,
      depressive symptoms, and functional impairment. Approximately 12-25% of anxious
      patients reported significant hoarding symptoms. Patients diagnosed with
      generalized anxiety disorder and obsessive-compulsive disorder were more likely
      to report significant hoarding symptoms than were those with panic disorder or
      specific phobia. Hoarding symptoms were positively correlated with trait anxiety,
      depressive symptoms, and functional impairment. These findings suggest that
      hoarding symptoms may be associated with anxiety disorders other than obsessive
      compulsive disorder. The findings further suggest that hoarding symptoms may be
      underreported by anxious populations since typical intake assessments do not
      include specific questions about hoarding and individuals with hoarding symptoms
      may be unlikely to spontaneously report them.

PMID- 20800428
TI  - Disgust and the development of posttraumatic stress among soldiers deployed to
      Afghanistan.
AB  - Although the DSM-IV recognizes that events can traumatize by evoking horror, not
      just fear, the role of disgust in the development of posttraumatic stress
      disorder (PTSD) has received little research attention. In a study of soldiers
      deployed to Afghanistan, we examined whether reports of peritraumatic disgust and
      trait disgust vulnerability factors (disgust propensity and disgust sensitivity)
      predict PTSD-symptoms, independently of peritraumatic fear, neuroticism, and
      anxiety sensitivity. Participants (N = 174) enrolled in this study before
      deployment, and were retested around 6 months (N = 138; 79%) and, again, 15
      months (N = 107; 62%) after returning home. The results showed that (1) greater
      peritraumatic disgust and fear independently predicted PTSD-symptom severity at 6
      months, (2) greater disgust propensity predicted more peritraumatic disgust, but
      not PTSD-symptom severity, and (3) disgust sensitivity moderated the relationship
      between peritraumatic disgust and PTSD-symptom severity. Implications of these
      findings for broadening the affective vulnerabilities that may contribute to PTSD
      will be discussed.

PMID- 20800429
TI  - Treatment of perigraft seroma in expanded polytetrafluoroethylene grafts by
      sequential fibrin sealing of the outer graft surface.
AB  - BACKGROUND: The recommended standard for treatment of perigraft seroma (PS) is
      the graft removal and the reconstruction using an alternative prosthesis. We
      assumed that a fibrin sealing of the outer surface of expanded
      polytetrafluoroethylene (ePTFE) grafts would prevent leakage and used this
      technique in the treatment and prevention of PS. METHODS: Over a 10-year period,
      24 patients were treated for PS after subcutaneous implantation of ePTFE grafts
      (14 arterial bypasses and 10 arteriovenous grafts). Affected graft segments were
      temporarily removed and underwent sequential fibrin sealing technique before
      reimplantation. In addition, an in vitro experiment was carried out to
      demonstrate the efficacy of fibrin sealing to prevent leakage through the ePTFE
      graft wall, after its hydrophobic barrier was destroyed by filling with saline
      solution under pressure. RESULTS: A cure of PS was observed in 20 patients (84%)
      at a follow-up period of 37 +/- 18 months. A later graft infection was not seen
      in any patient. The patency rate of reconstructed grafts appears to be
      unaffected. In the performed experiment we have demonstrated an elimination of
      leakage through the graft wall by the fibrin sealing technique. CONCLUSIONS:
      Sequential fibrin sealing of the outer surface is an effective way to treat PS in
      ePTFE grafts. However, failure of this treatment cannot be precluded. Further
      studies are necessary that may provide further insights into the causes and best
      treatment of PS and the possibly important role of PS in the aneurysm enlargement
      after complete endovascular exclusion with ePTFE endografts.

PMID- 20800430
TI  - Carotid endarterectomy: comparison between general and local anesthesia. Revision
      of our experience with 428 consecutive cases.
AB  - BACKGROUND: This sequential retrospective monocentric study compares the results
      between general and local anesthesia for carotid endarterectomy (CEA). METHODS:
      Between November 2002 and October 2004, 428 CEAs were performed in our vascular
      unit. Two groups were formed: group GA (general anesthesia): 219 patients
      operated under general anesthesia; group LA (local anesthesia): 209 patients
      operated under local anesthesia. RESULTS: No mortality was found in both groups.
      After surgery, three strokes were detected in group GA and three in group LA (GA
      1.36% vs. LA 1.43%, p = .9540); After CEA, there were three TIAs in GA group and
      none in LA group (GA 0.42% vs. LA 0%, p = .2634). CONCLUSION: The morbi-mortality
      was not influenced by the type of anesthesia used for carotid surgery. No
      statistical difference was detected in the perioperative neurological and
      cardiopulmonary complication rates between GA and LA.

PMID- 20800431
TI  - Bilateral post-traumatic carotid dissection as a result of a strangulation
      injury.
AB  - Carotid trauma is always very serious. Post-traumatic carotid dissection is
      rather rare and can be diagnosed late. Authors present a case report of post
      traumatic bilateral carotid dissection and its spontaneous recovery. Symptoms,
      diagnosis, and treatment are discussed.

PMID- 20800432
TI  - Combined femoral vein transposition and iliac vein to suprarenal vena cava bypass
      as a last resort dialysis access.
AB  - Patients undergoing hemodialysis are known to develop central venous occlusion
      and exhaust all options for vascular access to upper extremity sites; therefore,
      creating and maintaining vascular access is paramount in such patients. The
      present case report describes the condition of a 34-year-old woman with failed
      upper extremity access, frequent catheter-related issues, and multiple central
      venous occlusions. As a last resort, access to the lower extremity was pursued as
      follows: an inferior vena cava bypass was combined with a right femoral
      transposition fistula and a distal revascularization interval ligation procedure.
      This complex procedure that was carried out for the purpose of vascular access is
      a unique, albeit aggressive, surgical solution that resulted in autologous
      vascular access with a 6-month patency and also served to improve the quality of
      life in the seemingly hopeless case.

PMID- 20800433
TI  - Endovascular stenting for popliteal vascular entrapment is not recommended.
AB  - Endovascular techniques are often applied, but they have occasionally been
      reported in the treatment of popliteal vascular entrapment (PVE). A case of
      bilateral PVE is presented with an acute occlusion of the right popliteal artery.
      This was twice unsuccessfully treated with arterial recanalization and stenting
      at another Institution. The patient required an arterial reconstruction with his
      reversed saphenous vein, in addition to resection of the medial gastrocnemius
      muscle laterally inserted on his right limb. The left limb was treated with a
      simple myotomy. Recanalization and stenting is not recommended for PVE treatment.

PMID- 20800434
TI  - Recurrent cervical carcinoma presenting as a primary aortoduodenal fistula.
AB  - Aortoduodenal fistula is a rare cause of gastrointestinal (GI) bleeding, and
      carries high morbidity and mortality even in modern practice. Cervical carcinoma
      is a major health threat among adult women, and its recurrence is not uncommon.
      We herein present a case of primary aortoduodenal fistula because of recurrent
      cervical carcinoma. Our case demonstrated that diagnosis of primary aortoenteric
      fistula requires a high index of suspicion and a combination of diagnostic
      modalities to establish the diagnosis. Prompt diagnosis and rapid treatment are
      critical in reducing mortality and morbidity. Although rare, metastatic carcinoma
      can lead to aortoenteric fistula.

PMID- 20800435
TI  - Endovascular repair of an intraoperative thoracic aortic injury during all
      posterior vertebral column resection surgery.
AB  - Iatrogenic aortic injuries that occur during spinal procedures are rare but
      potentially lethal. When the posterior spinal approach is used, prone positioning
      and the need to prevent contamination of exposed bone and hardware adds
      complexity to the management of significant aortic injuries. We present a case of
      an intraoperative aortic injury that occurred during reoperative all-posterior
      vertebral column resection surgery that was successfully treated with emergent
      endograft deployment. The patient recovered without significant clinical
      sequelae. To our knowledge, this is the first reported case of intraoperative
      endovascular repair of a thoracic aortic injury incurred during posterior
      approach spinal surgery.

PMID- 20800436
TI  - Incidence and characteristics of venous thromboembolic disease during pregnancy
      and the postnatal period: a contemporary series.
AB  - BACKGROUND: To evaluate the incidence and characteristics of venous
      thromboembolic events (VTE) associated with pregnancy in a contemporary patient
      series. METHODS: We performed a retrospective review of 33,311 deliveries between
      June 2003 and June 2008. Patients with objective documentation of a VTE during
      pregnancy or the 3-month postnatal period were identified from hospital discharge
      International Classification of Disease Codes edition 9 codes. Diagnosis of deep
      venous thrombosis (DVT) was largely made by a Duplex ultrasound, whereas
      pulmonary embolism (PE) was diagnosed by a computerized tomographic angiography
      (CTA). RESULTS: Of 33,311 deliveries during the study period, 74 patients (0.22%)
      had a VTE. There were 40 incidents of DVT (0.12%) and 37 of PE (0.11%). DVT
      involved the iliac veins (6), the femoral or popliteal veins (16), the
      infrapopliteal veins (17), and the axillary vein (1). Most (57.5%) of the DVTs
      involved the left lower extremity. Thirty-eight (51.6%) of the VTEs occurred in
      the postnatal period, and of those 33 (87%) occurred within 1 week of delivery.
      Most of the postnatal VTEs (68%) were seen in patients who underwent a cesarean
      section. Among patients with VTE during pregnancy, there were 28% in the first
      trimester, 25% in the second, and 47% in the third. Events were distributed among
      maternal age groups as follows: 26% aged 13-24, 50% aged 25-34, and 24% aged 35
      54. Of the 35 patients tested for a hypercoagulable disorder, 12 were found to
      have a positive test result. Five (6.8%) of these 74 patients had a prior history
      of VTE, with two having a hypercoagulable disorder. In addition, 45 of the 74
      patients were on oral contraceptive therapy or received hormonal stimulation
      therapy before pregnancy. Patients with a VTE during pregnancy were treated with
      low molecular weight or unfractionated heparin. Most postnatal patients were
      treated with subcutaneous low molecular weight heparin and coumadin. Six inferior
      vena cava filters were placed in patients with bleeding complications as a result
      of anticoagulation. There were no deaths during the study period. CONCLUSIONS:
      Comparing our results with historic controls (DVT: 0.04-0.14% and PE: 0.003
      0.04%), the incidence of DVT in pregnancy has not changed significantly. We note,
      however, that the incidence of pulmonary embolus in our series is higher than
      previously reported. CTA has been used for the diagnosis of PE since the past
      decade. The increase in the rate of PE in the current series may be because of
      the higher sensitivity of CTA when compared with previous diagnostic modalities.

PMID- 20800437
TI  - Feasibility of quantitative ultrasound measurement of the heel bone in people
      with intellectual disabilities.
AB  - Low bone mineral density (BMD) and fractures are common in people with
      intellectual disabilities (ID). Reduced mobility in case of motor impairment and
      the use of anti-epileptic drugs contribute to the development of low BMD.
      Quantitative ultrasound (QUS) measurement of the heel bone is a non-invasive and
      radiation-free method for measuring bone status that can be used outside the
      hospital. QUS might be used for screening purposes to identify people with
      intellectual disability with poor bone status, who are in need of supplementary
      examination and treatment. To investigate feasibility of QUS in this group, QUS
      of the heel bone was performed on-site in 151 people with ID living in
      residential care. Measurements were successfully performed in at least one foot
      in 94.7%, were interpretable (resulting in a stiffness index) in 91.6%, and
      induced barely or no stress in 90.4% of the study population. Measurements
      generally took less than 10 min. In 93 persons bone status of both feet had been
      measured. The "mean percentage of the absolute difference" between outcomes of
      both feet was 15.5% (+/-15.3% SD, range 0-76.5%). Ultrasound measurement of the
      heel bone is a feasible and non-stressful method for measuring bone status in
      people with ID. Since the mean difference between outcomes of the left and right
      foot were large, measurement of both feet is recommended to prevent inaccurate
      interpretation.

PMID- 20800438
TI  - Translating shoulder computerized adaptive testing generated outcome measures
      into clinical practice.
AB  - STUDY DESIGN: Prospective longitudinal cohort study. INTRODUCTION: Increased use
      of computerized adaptive tests (CATs) to generate outcome measures during
      rehabilitation has stimulated questions concerning score interpretation. PURPOSE
      OF THE STUDY: The purpose of the study was to describe meaningful interpretations
      of scores from patient self-report shoulder functional status (FS) outcome
      measures estimated using a shoulder CAT (score range=0-100). METHODS: We applied
      four approaches to the clinical interpretation of outcomes data from 30,987
      patients with shoulder impairments receiving outpatient rehabilitation in 518
      clinics in 30 states (United States) between August 2007 and July 2009. First, we
      used standard error of estimates to construct 95% confidence intervals for each
      CAT estimated score. Second, we estimated the percentile rank (PR) of FS scores.
      Third, we used two threshold approaches to define individual patient-level
      change: statistically reliable change (i.e., minimal detectable change or MDC)
      and clinically important change. Fourth, we developed and applied a functional
      staging model, the Shoulder Function Classification System (SFCS). RESULTS:
      Precision of a single score was estimated by FS score +/-4. Based on score
      distribution, 25th, 50th, and 75th PRs corresponded to intake FS scores of 43,
      52, and 59 and discharge FS scores of 59, 68, and 80, respectively. MDC
      calculations indicated that changes in FS scores of 11 or more units represented
      statistically reliable change. FS score increments of eight or more units were
      estimated to represent minimal clinically important improvement based on receiver
      operating characteristic. The five-level SFCS was judged to be clinically logical
      and provide insight for clinical interpretation of patient progress. CONCLUSIONS:
      Results may improve clinical interpretation of CAT-generated outcome measures and
      assist clinicians using patient-reported outcomes during clinical practice. LEVEL
      OF EVIDENCE: Therapy level 2c.

PMID- 20800439
TI  - Different determinants of improvement of early and late systolic mitral
      regurgitation contributed after cardiac resynchronization therapy.
AB  - BACKGROUND: Functional mitral regurgitation (MR) at different phases of the
      regurgitant period may respond differently to cardiac resynchronization therapy
      (CRT). The aims of this study were to examine the impact of CRT on the phasic
      changes of MR (early vs late systole) and to explore the mechanisms of such
      changes. METHODS: Instantaneous MR flow rate and total MR volume were evaluated
      in 60 patients who had more than mild functional MR before and 3 months after
      CRT. In addition, indices of global left ventricular (LV) remodeling, mitral
      deformation, and LV systolic dyssynchrony were assessed. RESULTS: CRT diminished
      MR volume (38 +/- 18 vs 32 +/- 20 mL) by reducing both the early (72 +/- 47 vs 58
      +/- 48 mL/sec) and late (48 +/- 42 vs 40 +/- 42 mL/sec) systolic components (all
      p values < .01). In patients with >=10% reductions in total MR volume but not in
      patients without this improvement, there were significant reductions in LV end
      systolic volume, increases in LV +dP/dt, decreases in mitral valvular tenting,
      and improvements of systolic dyssynchrony at 3 months (all P values < .05). By
      multivariate regression, the reductions in LV end-systolic volume and tenting
      area were independent determinants of a reduction in total MR volume: the
      reductions in LV end-systolic volume and global dyssynchrony determined the
      reduction in early systolic MR, and the reductions in tenting area and global
      dyssynchrony determined reduction in late systolic MR. CONCLUSIONS: CRT decreases
      MR volume by reducing both early and late systolic MR. The determinants of the
      phasic improvement in functional MR are different.

PMID- 20800440
TI  - Advantage of right ventricular outflow tract pacing on cardiac function and
      coronary circulation in comparison with right ventricular apex pacing.
AB  - BACKGROUND: The purpose of this study was to investigate the acute effect of
      right ventricular outflow tract (RVOT) pacing and right ventricular apex (RVA)
      pacing on synchronous ventricular activation and coronary flow dynamics. METHODS:
      We enrolled 20 consecutive patients who underwent electrophysiologic study.
      Echocardiographic study including two-dimensional tissue tracking imaging and
      Doppler guide wire examination was performed during RVOT pacing and RVA pacing.
      RESULTS: The improvement of left ventricular radial dyssynchrony (99 +/- 12 ms
      vs. 142 +/- 16 ms, P < .001), time-averaged peak velocities of coronary blood
      flow (54 +/- 18 cm/s vs. 47 +/- 17 cm/s, P = .007), and coronary microvascular
      resistance index (2.0 +/- 0.8 vs. 2.4 +/- 1.1, P = .028) was observed with RVOT
      pacing compared with RVA pacing. CONCLUSION: RVOT pacing might provide favorable
      effects on the left ventricular function and coronary flow dynamics over RVA
      pacing.

PMID- 20800441
TI  - Future disability projections could be improved by connecting to the theory of a
      dynamic equilibrium.
AB  - OBJECTIVE: Projections of future trends in the burden of disability could be
      guided by models linking disability to life expectancy, such as the dynamic
      equilibrium theory. This article tests the key assumption of this theory that
      severe disability is associated with proximity to death, whereas mild disability
      is not. STUDY DESIGN AND SETTING: Using data from the GLOBE study (Gezondheid en
      Levensomstandigheden Bevolking Eindhoven en omstreken), the association of three
      levels of self-reported disabilities in activities of daily living with age and
      proximity to death was studied using logistic regression models. Regression
      estimates were used to estimate the number of life years with disability for life
      spans of 75 and 85 years. RESULTS: Odds ratios of 0.976 (not significant) for
      mild disability, 1.137 for moderate disability, and 1.231 for severe disability
      showed a stronger effect of proximity to death for more severe levels of
      disability. A 10-year increase of life span was estimated to result in a
      substantial expansion of mild disability (4.6 years) compared with a small
      expansion of moderate (0.7 years) and severe (0.9 years) disability. CONCLUSION:
      These findings support the theory of a dynamic equilibrium. Projections of the
      future burden of disability could be substantially improved by connecting to this
      theory and incorporating information on proximity to death.

PMID- 20800442
TI  - Published norms underestimate the health-related quality of life among persons
      with type 2 diabetes.
AB  - OBJECTIVE: To assess health-related quality of life (HRQL) among adults with type
      2 diabetes using the Short Form (SF)-36 and to obtain pooled estimates of HRQL
      for subpopulations defined by demographic characteristics, diabetes-related
      complications, and comorbidities. STUDY DESIGN AND METHODS: We conducted
      computerized searches of multiple electronic bibliographic databases, and studies
      in any language were selected in which HRQL was reported among adults with type 2
      diabetes using the SF-36. Estimates were combined using a random-effects model.
      RESULTS: One hundred eighteen studies fulfilled the inclusion criteria. HRQL was
      lower in persons with type 2 diabetes, as measured by all the eight component
      scores of the SF-36 when compared with the existing U.S. population norms and
      with previously published type 2 diabetes norms. SF-36 component and summary
      scores were extremely heterogeneous, and subpopulation data were sparse; this
      precluded obtaining meaningful pooled scores for most populations of interest and
      made comparisons among subpopulations difficult. CONCLUSION: Our data suggest
      that previously published norms may underestimate the effect of diabetes on HRQL,
      and diabetes populations are extremely heterogeneous, making broad population
      "norms" for HRQL in type 2 diabetes of limited use. Additional research with
      important subpopulations and individual-level data are needed to further explore
      the effect of diabetes on HRQL.

PMID- 20800443
TI  - Bayesian statistical method was underused despite its advantages in the
      assessment of implantable medical devices.
AB  - OBJECTIVE: We sought to review the use of Bayesian methods in the evaluation of
      the effectiveness of implantable medical devices (IMDs) to identify which areas
      of research need to be further investigated to improve IMD assessment. STUDY
      DESIGN AND SETTING: Relevant studies were identified by searching PubMed and the
      Food and Drug Administration Web site. Data were extracted independently by the
      two authors. The quality of Bayesian analysis reporting was summarized using the
      ROBUST (Reporting Of Bayes Used in clinical STudies) checklist. RESULTS:
      Seventeen studies met the inclusion criteria; five published meta-analyses and 12
      clinical studies were reported as FDA summaries of safety and effectiveness.
      Reporting of data was of high quality in meta-analyses, whereas it was of poor
      quality in clinical studies. Bayesian methods were used in meta-analyses to model
      study heterogeneity. In clinical studies, the objectives of the Bayesian analyses
      were mostly to address the question of equivalence and to use surrogate outcome
      predictors. Prior information, when reported, was less informative. Clinical data
      external to the trial itself and expert opinions were never used to elicit prior
      information. CONCLUSION: Our review highlighted the underuse of Bayesian methods
      in IMD assessment. The major challenge is to provide to clinical researchers a
      framework that helps them use external evidence to elicit prior distributions.

PMID- 20800444
TI  - The rhythm of chronic obstructive pulmonary disease exacerbations.

PMID- 20800445
TI  - Prospectively screening for eligible patients was inaccurate in predicting
      patient recruitment of orthopedic randomized trials.
AB  - OBJECTIVE: To compare the accuracy of estimates of potential recruitment from a
      prospective 8-week screening study compared with a retrospective chart review
      across sites participating in two fracture management trials. STUDY DESIGN AND
      SETTING: During the planning phase of two large, multicenter, randomized
      controlled fracture management trials, 74 clinical sites provided estimates of
      the annual recruitment rate both retrospectively (based on chart reviews) and
      prospectively. The prospective estimate was generated by screening, for 8 weeks,
      all incoming patients for eligibility in the concerning trial, without actually
      enrolling any patient. We compared these prospective and retrospective estimates
      with one another (for 74 sites in the two trials) and with actual 1-year
      recruitment rates in the definitive trial (for nine sites in one trial). RESULTS:
      There was a median difference of four patients (interquartile range: -14 to 18
      patients; P=0.89) between a center's prospective estimate and its retrospective
      estimate. Both predictions were overestimations of recruitment in the definitive
      trial; only 31% (95% confidence interval [CI]: 28, 35) of retrospectively
      estimated patients, and 31% (95% CI: 27, 35) of prospectively estimated patients
      were recruited in the definitive trials. CONCLUSION: Compared with relatively
      simple chart reviews, prospectively screening for eligible patients at clinical
      sites, which is associated with substantial costs, did not result in more
      accurate predictions of accrual in large, multicenter, randomized controlled
      trials.

PMID- 20800447
TI  - A threshold regression model for recurrent exacerbations in chronic obstructive
      pulmonary disease.
AB  - OBJECTIVE: Respiratory exacerbations are a major source of morbidity in patients
      with chronic obstructive pulmonary disease (COPD). In this article, we model COPD
      health status as a formal stochastic process. A successful model will provide a
      suitable statistical structure for analysis of the effects of medical
      interventions on a patient's health status, and, possibly, offer new insights
      into the underlying disease process. STUDY DESIGN AND SETTING: Our approach uses
      a regression methodology for time-to-event data called threshold regression (TR).
      We test the methodology on COPD data from a randomized clinical trial. Two TR
      models are studied: one based on a Poisson process and the other, a Wiener
      diffusion process. RESULTS: Both models provide reasonably accurate fits to the
      clinical trial data. The insights offered by the fitted models are interpreted.
      Analysis of the clinical trial data set using these TR models revealed that
      patients who experienced multiple exacerbations showed a progressive acceleration
      in rate of exacerbations, and successive shortening of stable intervals between
      exacerbations. CONCLUSION: TR techniques allow for realistic modeling of the COPD
      health state. A hybrid Poisson/Wiener diffusion TR model that incorporates the
      causal determinants of disease operating in each patient may be preferable.

PMID- 20800448
TI  - Predictive value of Medicare claims data for identifying revision of index hip
      replacement was modest.
AB  - OBJECTIVE: To determine the positive predictive value of Medicare claims for
      identifying revision of total hip replacement (THR), a frequent marker of THR
      quality and outcome. STUDY DESIGN AND SETTING: We obtained Medicare Part A
      (Hospital) claims from seven states on patients that had primary THR from July
      1995 through June 1996. We searched claims to determine whether these THR
      recipients had a subsequent revision THR through December 2006. We selected a
      sample of subjects with codes indicating both index primary and subsequent
      revision THR. We obtained medical records for both procedures to establish
      whether the revision occurred on the same side as index primary THR. RESULTS:
      Three hundred seventy-four subjects had codes indicating primary THR in 1995-96
      and subsequent revision. Seventy-one percent (95% confidence interval: 66, 76) of
      the revisions were performed on the index joint and would be correctly attributed
      as revisions of the index THR, using Medicare claims data. CONCLUSION: Claims
      data on revision THR that do not contain information on the side that was
      operated on are ambiguous with respect to whether the revision was performed on
      the index or contralateral side. Claims-based analyses of revisions after an
      index THR should acknowledge and adjust for this source of potential
      misclassification.

PMID- 20800449
TI  - N-of-1 clinical trials should be incorporated into clinical practice.
AB  - N-of-1 clinical trials have the potential to contribute to individual patient
      management and to the accrual of important information about populations.
      Incorporating these studies into clinical practice will require creative thinking
      so as to maintain rigor without excessive disruption of routine care.

PMID- 20800450
TI  - Validity and reliability of a nutrition screening tool in hospitalized patients.
AB  - OBJECTIVE: The British nutrition screening tool is a questionnaire designed to
      assess the nutrition status of hospitalized patients by nurses. The aim of this
      study was to evaluate the validity and reliability of this questionnaire in
      patients on admission to the hospital in Tehran. METHODS: For 6 mo, 446 patients
      aged over 18 y admitted to different wards of a general hospital were studied
      within the first 24 h of admission. A nutritionist undertook nutritional
      assessment in all patients to determine their nutritional status as an objective
      standard. Then a nurse completed the screening tool for patients. Results
      obtained using the screening tool were compared with those of the nutritional
      assessment to calculate the sensitivity, specificity, and predictive values. The
      interrater reliability of the tool was assessed by two nurses who completed the
      screening tool separately during the first 24 h following admission of each
      patient. It was also completed by a nurse within 2-d period of admission to test
      the intrarater reliability. RESULTS: Study participants included 229 women and
      217 men with mean age of 49.5 +/- 16.0 y. Sensitivity and specificity of the
      questionnaire were 86.7% (95% CI: 83.9-90.3%) and 61.7% (95% CI: 57.5-66.5%),
      respectively. Positive and negative predictive values were 79.1% (95% CI: 68.9
      77.1%) and 73.1% (95% CI: 75.1-82.9), respectively. The sensitivity of the tool
      was over 80% for both genders, for all body mass index grades, and for data
      obtained from gastroenterology, transplant, oncology, and hematology wards. The
      interrater reliability of screening tool was interpreted as substantial, being k
      = 0.68 and k = 0.74 on both the first and second days, respectively. The
      intrarater reliability of the screening tool was also interpreted as substantial,
      being k = 0.77. CONCLUSION: The nutrition screening tool is a simple, valid, and
      reliable tool that can be used by nurses to facilitate identification of patients
      requiring nutritional interventions.

PMID- 20800451
TI  - Low serum retinol and carotenoid levels in children and adolescents with AIDS:
      Does it really not matter?

PMID- 20800452
TI  - Clinical and laboratory characteristics in patients with acute myocardial
      infarction due to occlusive vasospasm.
AB  - BACKGROUND: The purpose of this study was to determine the clinical and
      laboratory characteristics in patients with acute myocardial infarction (AMI)
      associated with coronary vasospasm. METHODS AND RESULTS: Consecutive 231 patients
      with documented coronary vasospasm by ergonovine provocation test but with a
      normal-appearing coronary angiogram were divided into two groups, variant angina
      pectoris (VAP) patients (group I; n=202, 49.5 +/- 11.1 years) and AMI patients
      (group II; n=29, 47.4 +/- 11.2 years). Matched control patients were 84 AMI
      patients with significant stenosis (>50%) (group III; n=84, 61.2 +/- 11.8 years).
      Although, the incidence of hypertension, diabetes mellitus, and smoking were
      lower in group I than in group III, there was no difference between group II and
      III (diabetes, 7.9% vs. 13.8% vs. 29.8%; hypertension, 19.8% vs. 24.1% vs. 41.7%;
      smoking 48% vs. 48.3% vs. 61.9%; respectively, p<0.01). Measured high-sensitivity
      C-reactive protein (hsCRP) and fibrinogen level were higher (respectively,
      p<0.001, p<0.001) in groups II and III (group II, 1.88 +/- 2.9 mg/dl, 317.5 +/-
      51.2mg/dl; group III, 2.92 +/- 3.9 mg/dl, 326.8 +/- 107.7 mg/dl) than those in
      group I (0.68 +/- 1.5mg/dl, 263.2 +/- 70.3mg/dl). A correlation was clearly seen
      between fibrinogen and hsCRP (r=0.472, p<0.001). CONCLUSION: The clinical
      characteristics of patients with AMI associated with spasm were similar to those
      with VAP, but laboratory findings were similar to those of AMI in patients with
      significant stenosis.

PMID- 20800453
TI  - Vocational rehabilitation improves cognition and negative symptoms in
      schizophrenia.
AB  - Several studies in schizophrenia found a positive association between cognitive
      performance and work status, and it has been reported that good cognitive
      performance at the outset does predict the success of vocational interventions.
      However little has been done to investigate whether vocational interventions
      itself benefit cognitive performance. To test this hypothesis we performed a
      randomized, placebo-controlled trial to investigate in remitted schizophrenic
      patients the effect of a 6-months vocational rehabilitation program on cognitive
      performance. We recruited 112 remitted and clinically stable schizophrenic
      patients who aimed to enter a vocational rehabilitation program. From these, 57
      immediately entered a 6-months vocational rehabilitation program, whereas the
      remaining 55 were allocated to a waiting-list; the latter formed our control
      group, which received during the 6 months out-clinic follow-up treatment. Before
      and after the 6-months period we assessed changes in cognitive performance
      through a neuropsychological test battery, as well as changes in the
      psychopathological status and in quality of life. We found that vocational
      rehabilitation significantly improved patients' performance in cognitive measures
      that assess executive functions (concept formation, shifting ability,
      flexibility, inhibitory control, and judgment and critics abilities). Moreover,
      after 6 months the vocational group improved significantly in the negative
      symptoms and in quality of life, as compared to controls. Together with results
      from the literature, our findings reinforce the notion that the inclusion of
      vocational interventions may enhance the effectiveness of therapeutic strategies
      for schizophrenia patients.

PMID- 20800454
TI  - Serum TARC/CCL17 levels are increased in dermatomyositis associated with
      interstitial lung disease.

PMID- 20800455
TI  - Abnormal DNA methylation in skin lesions and PBMCs of patients with psoriasis
      vulgaris.

PMID- 20800456
TI  - Sorption of lanthanum and erbium from aqueous solution by activated carbon
      prepared from rice husk.
AB  - A biomass agricultural waste material, rice husk (RH) was used for preparation of
      activated carbon by chemical activation using phosphoric acid. The effect of
      various factors, e.g. time, pH, initial concentration and temperature of carbon
      on the adsorption capacity of lanthanum and erbium was quantitatively determined.
      It was found that the monolayer capacity is 175.4 mg g(-1) for La(III) and 250 mg
      g(-1) for Er(III). The calculated activation energy of La(III) adsorption on the
      activated carbon derived from rice husk was equal to 5.84 kJ/mol while it was 3.6
      kJ/mol for Er(III), which confirm that the reaction is mainly particle-diffusion
      controlled. The kinetics of sorption was described by a model of a pseudo-second
      order. External diffusion and intra-particular diffusion were examined. The
      experimental data show that the external diffusion and intra-particular diffusion
      are significant in the determination of the sorption rate. Therefore, the
      developed sorbent is considered as a better replacement technology for removal of
      La(III) and Er(III) ions from aqueous solution due to its low-cost and good
      efficiency, fast kinetics, as well as easy to handle and thus no or small amount
      of secondary sludge is obtained in this application.

PMID- 20800457
TI  - Surface plasmon resonance biosensor based on Fe3O4/Au nanocomposites.
AB  - In this paper, the core/shell Fe3O4/Au nanocomposites modified with 3
      mercaptopropionic acid (MPA) were prepared and applied in the surface plasmon
      resonance (SPR) biosensor. And the detailed investigation of Fe3O4/Au
      nanocomposites was separately performed by UV-vis spectroscopy and transmission
      electronic microscopy. As the magnetic property and exceptional optical
      properties, the Fe3O4/Au nanocomposites were used as the solid support for the
      goat anti-human IgM, which could be immobilized on the surface of SPR biosensor
      chip by a magnetic pillar. This novel method of immobilizing goat anti-human IgM
      simplified experimental procedures and facilitated the regeneration of the
      sensing membrane. In addition, the different diameter of Fe3O4/Au nanocomposites
      could be obtained with the different amount of MPA in the solution. And the
      effect of Fe3O4/Au nanocomposites with different diameters on the sensitivity of
      SPR biosensor was also explored. As a result, the SPR biosensor exhibits a
      satisfactory response for human IgM in the concentration range of 0.30-20.00 MUg
      ml(-1) and the increasing nanocomposite diameter is in favor of the sensitivity
      enhancement of SPR biosensor.

PMID- 20800458
TI  - Palliation of male genital cancers.
AB  - Advanced genital tumours are rare. Traditionally, surgical intervention in these
      patients has had a limited role due to the associated co-morbidities, poor
      performance status and overall poor prognosis. Because the potential benefit of
      surgical intervention in advanced cases is not evidence based, a large proportion
      of these patients are treated palliatively with chemoradiation therapy, which may
      have a limited role in advanced disease together with no significant improvement
      in quality of life for the patient. We present a review of palliative surgical
      techniques and non-surgical interventions in a range of male genital
      malignancies. Although the focus relates to advanced tumours with a palliative
      intent, a brief discussion on treatment with a view to cure is also covered. The
      traditional dogma is challenged with demonstration of value in surgery as part of
      multimodal therapy. Various surgical techniques that are used not only to excise
      the primary tumour, but also those of reconstruction of the urinary tract as well
      as techniques of flap and graft-based coverage are described. We show the
      essential role of surgery as part of multimodal therapy in well-motivated
      patients. No longer is surgery considered as having a limited role in these
      patients with advanced male genital malignancy.

PMID- 20800459
TI  - Nuclear imaging in three dimensions: a unique tool in cancer research.
AB  - Tumorigenesis includes alterations in the three-dimensional (3D) nuclear
      organization of the genome. The combination of sensitive quantitative fluorescent
      in situ hybridization (Q-FISH) and three-dimensional (3D) microscopy have evolved
      as powerful tools in studying the dynamic 3D organization of telomeres and
      chromosomes in the interphase nucleus of individual normal and tumor cells. Tumor
      specific alterations in 3D telomere architecture, particularly the appearance of
      telomeric aggregates, are early events in tumorigenesis and have diagnostic and
      prognostic value. Novel tools in the 3D nuclear imaging arsenal now include high
      throughput scanning capabilities and new 3D nano-resolution microscopy of tissues
      and cells. In this review, we summarize our current understanding of the biology
      of telomeres in the context of tumorigenesis and elucidate the important
      integrating function of advanced 3D imaging technologies in translating new
      discoveries in basic cancer research into new diagnostic tools for clinical
      oncologists to improve patient care.

PMID- 20800460
TI  - Occurrence and diversity of lipids in modern coral skeletons.
AB  - Coral skeletons are composite acellular structures, in which organic
      macromolecules are intimately associated with mineral phases. Previous studies
      focussed on proteins and sugars of the soluble organic matrices extracted from
      the skeletons. Here we report the occurrence of diverse lipids which were
      extracted from the aragonitic skeletons of seven modern coral species. Using thin
      layer chromatography, we show that these lipids differ in quantity and
      composition between the species. Higher proportions of sterols and sterol esters
      in skeleton extracts as compared to a much higher abundance of waxes and
      triglycerides in previously studied extracts from scleractinian soft tissues
      suggest a specific, although not yet determined, role in biomineralization. The
      occurrence of intraskeletal lipids along with other organic components should
      also be taken into account when using coral skeletons as bone allografts, as well
      as in fossilization processes.

PMID- 20800461
TI  - Limits to sustainable energy budget during lactation in the striped hamster
      (Cricetulus barabensis) raising litters of different size.
AB  - A female animal appears to approach an upper limit to the rate of sustained
      energy intake/metabolic rate (SusEI/MR) during lactation. However, different
      species of animals may respond differently to the sustainable limit. Here, we
      measured energy budget during lactation in female striped hamsters raising
      litters of natural size (Con), and females whose litter size was manipulated
      during early lactation to support fewer or more pups (minus pups, MP or plus
      pups, PP). The striped hamsters significantly decreased their body mass and
      increased food intake from early to late lactation; and MP females had lower
      weight loss and food intake than the control and PP females. Litter size of the
      PP group decreased significantly over the period of lactation, and pups were
      weaned at a similar weight to that of the controls. MP females supported a
      significantly lower litter mass throughout lactation compared with the control
      and PP females, but during late lactation the pups from the MP group were
      significantly heavier. Resting metabolic rate (RMR) did not differ significantly
      between the three groups and the gross energy intake during peak lactation was
      5.0 *, 4.2 * and 5.0 * RMR for the control, MP and PP females, respectively.
      Female striped hamsters reached a plateau in food intake at around 14 g/d during
      peak lactation, which might signify a limit of SusEI at 5.0 * RMR. However, it
      was not possible to determine whether the limitation on SusEI was imposed
      centrally by the capacity of the gastrointestinal tract to process food,
      peripherally by the capacity of the mammary gland to produce milk, or by the
      capacity of animals to dissipate heat.

PMID- 20800463
TI  - Prevalence and factors related to syringe sharing behaviours among female
      injecting drug users who are also sex workers in China.
AB  - BACKGROUND: Female injecting drug users who are sex workers (IDUFSWs) are at high
      risk of contracting HIV. They may bridge HIV transmissions from injecting drug
      users to clients of female sex workers. METHODS: A total of 216 non
      institutionalised IDUFSWs were recruited by snowball sampling methods. Anonymous
      face-to-face interviews were conducted to collect data. Univariate, multivariate
      and hierarchical logistic regression models were fitted to investigate the
      associations between background characteristics, cognitive variables,
      psychological stress and syringe sharing behaviours among IDUFSWs. RESULTS:
      Respectively 33.8% and 27.8% of the respondents injected drugs with others' used
      syringes and gave used syringes to others for drug injection in the last month.
      These two syringe sharing behaviours were significantly associated with
      inconsistent condom use during commercial sex (OR=5.00 and 1.92, p<0.05). Over
      90% of the respondents reported at least one type(s) of psychological distress
      included in this study. Adjusting for significant background variables, all
      variables that are related to the Theory of Planned Behaviour (attitude, norm,
      perceived control and behavioural intention) and psychological distress (except
      for depression) were significantly associated with injecting drugs with others'
      used syringes (adjusted OR=2.08-6.25, p<0.05), whilst variables related to
      perceived control, behavioural intention and insomnia were significantly
      associated with providing used syringes to others for injection (adjusted OR=2.00
      3.56, p<0.05). In two separate summary multivariate models, variables related to
      the Theory of Planned Behaviours and psychological distress were independently
      associated with injecting drugs with others' used syringes (OR=1.98-4.02, p<0.05)
      and giving used syringes to others for injection (OR=2.06-3.59, p<0.05).
      CONCLUSIONS: Syringe sharing behaviours were prevalent among IDUFSWs and were
      associated with cognitive and psychological factors. Effective integrative
      intervention programmes targeting IDUFSWs are warranted.

PMID- 20800462
TI  - Infrequent opioid overdose risk reduction behaviours among young adult heroin
      users in cities with wide coverage of HIV prevention programmes.
AB  - BACKGROUND: Opioid overdose risk reduction behaviours include some preventive
      behaviours to avoid overdoses (PB) and others to avoid death after overdose, such
      as never using heroin while alone (NUA). Few studies have examined the prevalence
      and predictors of these behaviours. AIM: To establish the prevalence and
      predictors of PBs and NUA among heroin users, both injectors and non-injectors,
      in three Spanish cities. METHODS: 516 injecting and 475 non-injecting heroin
      users aged 18-30 were street-recruited in 2001-2003 and interviewed by face-to
      face computer-assisted interview. PBs and NUA in the last 12 months were explored
      using open-ended and precoded questions, respectively. Specific predictors for
      three PB categories were investigated: control of route of drug administration,
      control of quantity or type of heroin used, and control of co-use of other drugs.
      Bivariate and logistic regression methods were used. RESULTS: Overall, the most
      prevalent PBs were: using a stable and not excessive amount of heroin (12.7%),
      injecting or using the whole heroin dose slowly or dividing it into smaller doses
      (12.4%), reducing or stopping heroin injection (8.3%), and not mixing heroin with
      tranquillisers (5.1%). Most PBs were significantly more prevalent among injectors
      than non-injectors. No one mentioned reducing the amount of heroin after an
      abstinence period. Some 36.2% had NUA. In multiple regression analysis, knowledge
      of risk factors for opioid overdose was a predictor of specific PBs, although
      this was not always the case. Use of syringe exchange programmes was a predictor
      of PB among injectors. However, attending methadone maintenance treatment (MMT)
      or other drug-dependence treatment was not a predictor of any opioid overdose
      reduction behaviour. Only ever having witnessed or experienced an overdose
      predicted PB in both injectors and non-injectors. CONCLUSIONS: The proportion of
      heroin users with opioid overdose risk reduction behaviours is very low.
      Additional specific measures to prevent overdose are needed, as well as increased
      emphasis on reducing the risk of overdose in programmes to prevent HIV and other
      blood-borne infections in heroin injectors.

PMID- 20800464
TI  - Managing la malilla: Exploring drug treatment experiences among injection drug
      users in Tijuana, Mexico, and their implications for drug law reform.
AB  - BACKGROUND: In August 2009, Mexico reformed its drug laws and decriminalized
      small quantities of drugs for personal use; offenders caught three times will be
      mandated to enter drug treatment. However, little is known about the quality or
      effectiveness of drug treatment programs in Mexico. We examined injection drug
      users' (IDUs) experiences in drug treatment in Tijuana, Mexico, with the goal of
      informing program planning and policy. METHODS: We examined qualitative and
      quantitative data from Proyecto El Cuete, a multi-phased research study on HIV
      risk among IDUs in Tijuana. Phase I consisted of 20 in-depth interviews and Phase
      II employed respondent-driven sampling to recruit 222 IDUs for a quantitative
      survey. We also reviewed national drug policy documents, surveillance data, and
      media reports to situate drug users' experiences within the broader
      sociopolitical context. RESULTS: Participants in the qualitative study were 50%
      male with a mean age of 32; most injected heroin (85.0%) and methamphetamine
      (60.0%). The quantitative sample was 91.4% male with a mean age of 35; 98.2%
      injected heroin and 83.7% injected heroin and methamphetamine together. The
      majority of participants reported receiving treatment: residential treatment was
      most common, followed by methadone; other types of services were infrequently
      reported. Participants' perceptions of program acceptability and effectiveness
      were mixed. Mistreatment emerged as a theme in the qualitative interviews and was
      reported by 21.6% of Phase II participants, primarily physical (72.0%) and verbal
      (52.0%) abuse. CONCLUSIONS: Our results point to the need for political,
      economic, and social investment in the drug treatment system before offenders are
      sentenced to treatment under the revised national drug law. Resources are needed
      to strengthen program quality and ensure accountability. The public health impact
      of the new legislation that attempts to bring drug treatment to the forefront of
      national drug policy should be systematically evaluated.

PMID- 20800466
TI  - Differential spectral phase interferometry for wide dynamic range surface plasmon
      resonance biosensing.
AB  - We introduce a novel wide dynamic range phase-sensitive surface plasmon resonance
      (SPR) biosensor based on differential spectral interferometry. Superseding
      conventional spectroscopic approach where only the SPR dip is monitored, our
      system acquires the spectral phase information of the entire electromagnetic
      field that undergoes SPR transformation. Since the SPR-induced phase change is
      highly wavelength specific with fixed incident angle, ultra-high sensitivity
      achievable through phase-sensitive detection, as reported herein, is maintained
      continuously across the spectral domain in response to refractive index changes.
      Our system has demonstrated a detection limit of 2.2*10(-7) in terms of
      refractive index unit (RIU) using standard single-layer gold surface. In terms of
      biosensing performance, the estimated detection sensitivity obtained from bovine
      serum albumin (BSA) antibody-antigen binding experiments is 0.5 ng ml(-1).

PMID- 20800465
TI  - Group sex events amongst non-gay drug users: an understudied risk environment.
AB  - This article discusses relevant literature on group sex events--defined as events
      at which some people have sex with more than one partner--as risk environments,
      with a particular focus on group sex events where people who take drugs by non
      injection routes of administration participate and where the event is not
      primarily LGBT-identified, at a "classic" crack house, nor in a brothel. It also
      briefly presents some findings from a small ethnography of such events. Group sex
      participation by people who take drugs by non-injection routes of administration
      seems to be widespread. It involves both behavioural and network risk for HIV and
      STI infection, including documented high-risk behaviour and sexual mixing of STI-
      and HIV-infected people with those who are uninfected. Indeed several HIV and STI
      outbreaks have been documented as based on such group sex events. Further, group
      sex events often serve as potential bridge environments that may allow infections
      to pass from members of one high-risk-behavioural category to another, and to
      branch out through these people's sexual and/or injection networks to other
      members of the local community. The ethnographic data presented here suggest a
      serious possibility of "third party transmission" of infectious agents between
      people who do not have sex with each other. This can occur even when condoms are
      consistently used since condoms and sex toys are sometimes used with different
      people without being removed or cleaned, and since fingers and mouths come into
      contact with mucosal surfaces of other members of the same or opposite sex. In
      addition to being risk environments, many of these group sex events are venues
      where risk-reducing norms, activities and roles are present--which lays the basis
      for harm reduction interventions. Research in more geographical locations is
      needed so we can better understand risks associated with group sex events in
      which drug users participate--and, in particular, how both participants and
      others can intervene effectively to reduce the risks posed to participants and
      non-participants by these group sex events. Such interventions are needed and
      should be developed.

PMID- 20800467
TI  - Recording electric potentials from single adherent cells with 3D microelectrode
      arrays after local electroporation.
AB  - This short communication reports on the innovative method of the local micro
      invasive needle electroporation (LOMINE) of single adherent cells. The
      investigation of cellular reactions in living cell cultures represents a
      fundamental method, e.g. for drug development and environmental monitoring.
      Existing classical methods for intracellular measurements using, e.g. patch clamp
      techniques are time-consuming and complex. Present patch-on-chip systems are
      limited to the investigation of single cells in suspension. Nevertheless, the
      most part of the cells of the human body is adherently growing. Therefore, we
      develop a new chip system for the growth of adherent cells with 64 micro
      structured needle electrodes as well as 128 dielectrophoretic electrodes, located
      within a measuring area of 1 mm(2). With this analytical chip, the intracellular
      investigation of electro-chemical changes and processes in adherently growing
      cells will become possible in the near future. Here, we present first
      intracellular measurements with this chip system.

PMID- 20800468
TI  - Aptamer-based biosensor for sensitive PDGF detection using diamond transistor.
AB  - The detection of platelet-derived growth factor (PDGF) via a solution-gate field
      effect transistor (SGFET) has been demonstrated for the first time using aptamers
      immobilized on a diamond surface. Upon introduction of PDGF to the immobilized
      aptamer, a shift of 31.7 mV in the negative direction is observed at a source
      drain current of -50 MUA. A shift of 32.3 mV in the positive direction is
      detected after regeneration by SDS solution, indicating that the static
      measurement returns to its original value. These SGFETs operate stably within the
      large potential window of diamond (>3.0 V), and hence the surface channel does
      not need passivating with a thick insulating layer. Thereof, the immobilized
      aptamer channels have been exposed directly to the electrolyte solution without a
      gate insulator. Immobilization is achieved via aptamers covalently bonding to
      amine sites, thereby increasing the sensitivity of the biosensors. Diamond SGFETs
      have potential for the detection of PDGF and show durability against biological
      degradation after repeated usage and regeneration.

PMID- 20800469
TI  - Highly sensitive and reversible silicon nanowire biosensor to study nuclear
      hormone receptor protein and response element DNA interactions.
AB  - To thoroughly understand the role that estrogen receptors partake in regulation
      of gene expression, characterization of estrogen receptors (ERs) and estrogen
      response elements (EREs) interactions is essential. In the work, we present a
      highly sensitive and reusable silicon nanowire (SiNW) biosensor to study the
      interactions between human ER proteins (ER, alpha and beta subtypes) and EREs
      (dsDNA). The proteins were covalently immobilized on the SiNW surface. Various
      EREs including wild-type, mutant and scrambled DNA sequences were then applied to
      the protein-functionalized SiNW surface. Due to negatively charged dsDNA, binding
      of the EREs to the ERs on the n-type SiNW biosensor leads to the accumulation of
      negative charges on the surface, thereby inducing increase in resistance. The
      results show that the specificity of the ERE-ERalpha binding is higher than that
      of the ERE-ERbeta binding, what is more, the mutant ERE reduces the binding
      affinity for both ERalpha and ERbeta. By applying various concentrations of wild
      type ERE to the bound ERalpha, a very low concentration of 10 fM wild-type ERE
      was found to be able to bind to the ERalpha. The reversible association and
      dissociation between ERalpha and wt-ERE was achieved, pointing to a reusable
      biosensor for protein-DNA binding. Through the study, we have established the
      SiNW biosensor as a promising method in providing comprehensive study for hormone
      receptor-response element interactions.

PMID- 20800470
TI  - Chemical and biological sensing applications based on graphene field-effect
      transistors.
AB  - Chemical and biological sensors based on graphene field-effect transistors (G
      FETs) were investigated. A single-layer of graphene was prepared by mechanical
      cleavage of natural graphite. The G-FETs were driven by a reference-gate
      operating in buffer solution, and exhibited very good transport characteristics.
      The G-FETs detected the pH value of the solution with high precision. The Dirac
      point shifted in the positive direction with increasing pH of the solution. The
      detection limit (signal/noise=3) for measuring changes in the pH of the solution
      was estimated to be 0.025, indicating the high sensitivity of the G-FETs.
      Moreover, the devices electrically detected proteins with different charge types.
      The drain current decreased (increased) when positively (negatively) charged
      proteins were added to the solution. These results indicate that the G-FETs are
      among the most suitable candidates for FET-based chemical and biological sensors.

PMID- 20800472
TI  - Control of embryonic stem cell identity by nucleosome remodeling enzymes.
AB  - Embryonic stem (ES) cells are pluripotent cells that can self-renew indefinitely
      or be induced to differentiate into multiple cell lineages, and thus have the
      potential to be used in regenerative medicine. Pluripotency transcription factors
      (TFs), such as Oct4, Sox2, and Nanog, function in a regulatory circuit that
      silences the expression of key TFs required for differentiation and activates the
      expression of genes important for maintenance of pluripotency. In addition,
      proteins that remodel chromatin structure also play important roles in
      determining the ES cell-specific gene expression pattern. Here we review recent
      studies demonstrating the roles of enzymes that carry out one facet of chromatin
      regulation, nucleosome remodeling, in control of ES cell self-renewal and
      differentiation.

PMID- 20800471
TI  - Photogenerated carbohydrate microarrays to study carbohydrate-protein
      interactions using surface plasmon resonance imaging.
AB  - A photochemical strategy to generate carbohydrate microarrays on flat sensor
      surfaces, and to study the protein-binding effects of these arrays by surface
      plasmon resonance imaging is described. The approach was validated using a panel
      of carbohydrate-binding proteins. The coupling agents, thiol-functionalized
      perfluorophenyl azides, allow the covalent attachment of underivatized
      carbohydrates to gold surfaces by a fast photochemical reaction. Carbohydrate
      microarrays composed of 3,6-di-O-(alpha-D-mannopyranosyl)-D-mannopyranose (Man3),
      2-O-alpha-D-mannopyranosyl-D-mannopyranose (Man2), D-mannose (Man), D-glucose
      (Glc), and D-galactose (Gal) were constructed, and the binding studies were
      carried out in real-time using surface plasmon resonance imaging. Results showed
      that the immobilized carbohydrate ligands retained their binding affinities with
      lectins, the rank order of which was consistent with that of the free ligands in
      solution. The detection limit of Man3, Man2, Man, and Glc with the lectin
      Concanavalin A was measured to be 0.29 nM, 0.18 nM, 0.61 nM, and 3.1 nM,
      respectively. In addition, soybean agglutinin and Griffonia simplicifolia lectin
      II were tested on the array, and the results were consistent with the binding
      selectivity of these lectins with the carbohydrate ligands.

PMID- 20800473
TI  - The single dendritic branch as a fundamental functional unit in the nervous
      system.
AB  - The conventional view of dendritic function is that dendrites collect synaptic
      input and deliver it to the soma. This view has been challenged in recent years
      by new results demonstrating that dendrites can act as independent processing and
      signalling units, performing local computations that are then broadcast to the
      rest of the neuron, or to other neurons via dendritic transmitter and
      neuromodulator release. Here we describe these findings and discuss the notion
      that the single dendritic branch may represent a fundamental unit of signalling
      in the mammalian nervous system. This view proposes that the dendritic branch is
      a basic organizational unit for integrating synaptic input, implementing synaptic
      and homeostatic plasticity, and controlling local cellular processes such as
      protein translation.

PMID- 20800474
TI  - A step-by-step guide to visual circuit assembly in Drosophila.
AB  - The ability of vertebrates and insects to perceive and process information about
      the visual world is mediated by neural circuits, which share a strikingly
      conserved architecture of reiterated columnar and layered synaptic units. Recent
      genetic approaches conferring single-cell resolution have enabled major advances
      in our understanding of the cellular and molecular strategies that orchestrate
      visual circuit assembly in Drosophila. Photoreceptor axon targeting relies on a
      sequence of interdependent developmental steps to achieve temporal coordination
      with the formation and maturation of partner neurons. Distinct targeting events
      depend on anterograde and autocrine signaling, neuron-glia interactions, axon
      tiling and the timely expression of homophilic cell surface molecules. These
      mediate local adhesive or repulsive interactions of photoreceptor axons with each
      other and with target neurons.

PMID- 20800476
TI  - Combustion and NO emission of high nitrogen content biomass in a pilot-scale
      vortexing fluidized bed combustor.
AB  - The combustion of biomass of various nitrogen contents and its NO emission were
      investigated experimentally in this study. All the experiments were conducted in
      an I.D. 0.45 m pilot-scale vortexing fluidized bed combustor (VFBC). Rice husk,
      corn, and soybean were used as feeding materials. Urea was added into the feeding
      materials for the purpose of adjusting nitrogen content. The effects of various
      operating parameters on NO emission, such as bed temperature, excess air ratio,
      and flow rate of secondary air, were investigated. The effects of nitrogen
      content of fuels on NO emissions were also investigated by using the mixtures of
      rice husk/soybean, rice husk/urea, corn/soybean, and corn/urea in various weight
      ratios. The NO concentrations at various positions in the combustor were sampled
      and recorded. The experimental results show that most nitric oxide is formed at
      just above the bed surface. Temperature and excess air ratio are the major
      operating parameters for NO emission. For biomass with high nitrogen content, NO
      emission decreases with excess air, and increases with bed temperature. Compared
      with char-N, volatile-N is the more dominant reactant source for NO emission.

PMID- 20800475
TI  - A phase 2 study of vatalanib in metastatic melanoma patients.
AB  - BACKGROUND: A phase 2 study of vatalanib (PTK787/ZK222584) an oral tyrosine
      kinase inhibitor of VEGFR 1, 2 and 3 was undertaken in patients with metastatic
      melanoma. METHODS: Adults with pathologically confirmed metastatic melanoma, WHO
      Performance status 0-2, and adequate haematological, hepatic and renal function,
      were treated with vatalanib until disease progression. The trial used Fleming's
      single stage design. RESULTS: Tumour control rate (CR+PR+SD) was 35% at 16 weeks,
      with objective response seen in only 1 patient. Median progression-free survival
      was 1.8 months (95% CI 1.8-3.7 months) and median overall survival was 6.5 months
      (95% CI 3.9-10.2 months). CONCLUSION: Vatalanib stabilised disease in a
      proportion of patients, although overall survival was disappointing.

PMID- 20800477
TI  - Chemical reaction- and particle diffusion-based kinetic modeling of metal
      biosorption by a Phormidium sp.-dominated cyanobacterial mat.
AB  - The present study explores the suitability of chemical reaction-based and
      diffusion-based kinetic models for defining the biosorption of Cu(II), Cd(II) and
      Pb(II) by Phormidium sp.-dominated mat. The time-course data of metal sorption by
      the test mat significantly (r2=0.932-0.999) fitted to the chemical reaction-based
      models namely pseudo-first-order, -second-order, and the general rate law.
      However, these models fail to accurately describe the kinetics of metal
      biosorption due either to prefixed order or unjustifiable change in rate constant
      and reaction order with varying concentrations of metal and biomass in the
      solution. The diffusion-based models, namely, the intra-particle diffusion model
      and the external mass transfer model fitted well to the time-course metal
      sorption data, thus suggesting involvement of both external and intra-particle
      diffusion processes in sorption of test metals by mat biomass. However, the Boyd
      kinetic expression clearly showed that the external mass transfer is the dominant
      process.

PMID- 20800478
TI  - Bio-kinetic analysis on treatment of textile dye wastewater using anaerobic batch
      reactor.
AB  - An anaerobic digestion technique was applied to textile dye wastewater aiming at
      the colour and COD removal. Pet bottles of 5 L capacity were used as reactor
      which contains methanogenic sludge of half a liter capacity which was used for
      the treatment of combined synthetic textile dye and starch wastewater at
      different mixing ratios of 20:80, 30:70, 40:60, 50:50 and 60:40 with initial COD
      concentrations as 3520, 3440, 3360, 3264 and 3144 mg L(-1), respectively. The
      reactor was maintained at room temperature (30+/-3 degrees C) with initial pH of
      7. The maximum COD and colour removal were 81.0% and 87.3% at an optimum mixing
      ratio of 30:70 of textile dye and starch wastewaters. Both Monod's and Haldane's
      models were adopted in this study. The kinetic constants of cell growth under
      Haldane's model were satisfactory when compared to Monod's model. The kinetic
      constants obtained by Haldane's model were found to be in the range of
      MUmax=0.037-0.146 h(-1), Ks=651.04-1372.88 mg L(-1) and Ki=5681.81-18727.59 mg L(
      1).

PMID- 20800479
TI  - Switch control pocket inhibitors of p38-MAP kinase. Durable type II inhibitors
      that do not require binding into the canonical ATP hinge region.
AB  - Switch control pocket inhibitors of p38-alpha kinase are described. Durable type
      II inhibitors were designed which bind to arginines (Arg67 or Arg70) that
      function as key residues for mediating phospho-threonine 180 dependant
      conformational fluxing of p38-alpha from an inactive type II state to an active
      type I state. Binding to Arg70 in particular led to potent inhibitors,
      exemplified by DP-802, which also exhibited high kinase selectivity. Binding to
      Arg70 obviated the requirement for binding into the ATP Hinge region. X-ray
      crystallography revealed that DP-802 and analogs induce an enhanced type II
      conformation upon binding to either the unphosphorylated or the doubly
      phosphorylated form of p38-alpha kinase.

PMID- 20800480
TI  - Synthesis and molecular docking study of novel coumarin derivatives containing
      4,5-dihydropyrazole moiety as potential antitumor agents.
AB  - A series of novel coumarin derivatives containing 4,5-dihydropyrazole moiety as
      potential telomerase inhibitors were synthesized. The bioassay tests show that
      compound 3d exhibited potentially high activity against human gastric cancer cell
      SGC-7901 with IC(50) value of 2.69 +/- 0.60 MUg/mL. All title compounds were
      assayed for telomerase inhibition by a modified TRAP assay, the results show that
      compounds 3d and 3f can strongly inhibit telomerase with IC(50) values of 2.0 +/-
      0.07 and 1.8 +/- 0.35 MUM, respectively. Docking simulation was performed to
      position compound 3d into the telomerase (3DU6) active site to determine the
      probable binding model.

PMID- 20800481
TI  - Synthesis and cytotoxicity of some biurets against human breast cancer T47D cell
      line.
AB  - Design, synthesis and cytotoxicity of several known and novel biurets against
      human breast cancer T47D cell line in comparison to doxorubicin are described.
      Biurets incorporating 2-methyl quinoline-4-yl and benzo[d]thiazol-2-ylthio
      moieties showed higher cytotoxicity and decreased cell viability in a
      concentration- and time-dependent manner.

PMID- 20800482
TI  - Synthesis and biological evaluation of novel coumarin-based inhibitors of Cdc25
      phosphatases.
AB  - The cell division cycle 25 (Cdc25) family of proteins are dual specificity
      phosphatases that activate cyclin-dependent kinase (CDK) complexes, which in turn
      regulate progression through the cell division cycle. Overexpression of Cdc25
      proteins has been reported in a wide variety of cancers; their inhibition may
      thus represent a novel approach for the development of anticancer therapeutics.
      Herein we report new coumarin-based scaffolds endowed with a selective inhibition
      against Cdc25A and Cdc25C, being 6a and 6d the most efficient inhibitors and
      worthy of further investigation as anticancer agents.

PMID- 20800483
TI  - Novel indoline-1- or 3,4-dihydroquinoline-1(2H)-substituted carbothiohydrazides
      as TPO receptor agonists.
AB  - Synthesis and evaluation of novel series of indoline-1- or 3,4-dihydroquinoline
      1(2H)-substituted carbothiohydrazide or carbohydrazide based small molecule
      compounds as thrombopoietin (TPO) receptor agonists are reported. Members of
      these compounds have been identified as full agonists of human c-mpl in BaF3/TPOR
      cell line. Indoline-1-carbohydrazide 9b exhibited reasonable pharmacokinetic
      profile.

PMID- 20800484
TI  - Reverse-benzamidine antimalarial agents: design, synthesis, and biological
      evaluation.
AB  - In the frame of the development of bis-cationic choline analogs, the RSA of bis-N
      alkylamidines were studied and a new series of reverse-benzamidine derivatives
      was designed. Contrary to the lipophilicity, the basicity of alkylamidine
      compounds directly influences their antimalarial potencies.

PMID- 20800485
TI  - On resin amino acid side chain attachment strategy for the head to tail synthesis
      of new glutamine containing gramicidin-S analogs and their antimicrobial
      activity.
AB  - The alarming increase in infections caused by multiple drug resistant bacteria
      including methicillin-resistant Staphylococcus aureus has prompted a desperate
      search for new antimicrobials. Augmenting the discoveries of completely new
      scaffolds with antimicrobial activity are efforts aimed at modifying existing
      molecules to optimize activity or reduce toxicity. We report herein the parallel
      solid-phase synthesis of analogues of the cationic antimicrobial peptide
      gramicidin S (GS) using amino acid side chain attachment strategy. The ornithine
      (Orn) residues were replaced by glutamine (Gln) and the aromatic D-phenylalanine
      (Phe) were replaced by different aromatic D-amino acids. Additional Gln
      containing GS analogues with all the possible combinations of the hydrophobic
      amino acids valine and leucine were also synthesized. In this work we also report
      the antibacterial activity of these analogs against several clinically-important
      drug-resistant Gram-positive and Gram-negative pathogens.

PMID- 20800486
TI  - Identification of a novel selective H1-antihistamine with optimized
      pharmacokinetic properties for clinical evaluation in the treatment of insomnia.
AB  - Analogs of the known H(1)-antihistamine R-dimethindene with suitable selectivity
      for key GPCRs, P450 enzymes and hERG channel were assessed for metabolism profile
      and in vivo properties. Several analogs were determined to exhibit diverse
      metabolism. One of these compounds, 10a, showed equivalent efficacy in a rat
      EEG/EMG model to a previously identified clinical candidate and a potentially
      superior pharmacokinetic profile as determined from a human microdose study.

PMID- 20800487
TI  - Synthesis and evaluation of novel chloropyrrole molecules designed by molecular
      hybridization of common pharmacophores as potential antimicrobial agents.
AB  - In an attempt to identify new potential lead as antimicrobial agent, 31 novel
      chloropyrrole derivatives of aroyl hydrazones and chalcones incorporating common
      pharmacophore of pyoluteorin derivatives were synthesized. Antimicrobial activity
      of the synthesized compounds was evaluated using broth dilution technique. Based
      on biological evaluation data it was observed that activity increases as the
      number of chlorines on pyrrole core increases. Few 1H-pyrrole-2-carbohydrazide
      derivatives shows activity equivalent to the standard drug ciprofloxacin. Thus,
      these compounds can act as potential lead for further antibacterial studies.

PMID- 20800488
TI  - Imaging of transgenic cricket embryos reveals cell movements consistent with a
      syncytial patterning mechanism.
AB  - The mode of insect embryogenesis varies among species, reflecting adaptations to
      different life history strategies [1, 2]. In holometabolous insects, which
      include the model systems, such as the fruit fly and the red flour beetle, a
      large proportion of the blastoderm produces an embryo, whereas hemimetabolous
      embryos generally arise from a small region of the blastoderm [3]. Despite their
      importance in evolutionary studies, information of early developmental dynamics
      of hemimetabolous insects remains limited. Here, to clarify how maternal and gap
      gene products act in patterning the embryo of basal hemimetabolous insects, we
      analyzed the dynamic segmentation process in transgenic embryos of an
      intermediate-germ insect species, the cricket, Gryllus bimaculatus. Our data
      based on live imaging of fluorescently labeled embryonic cells and nuclei suggest
      that the positional specification of the cellular blastoderm may be established
      in the syncytium, where maternally derived gradients could act fundamentally in a
      way that is similar to that of Drosophila, namely throughout the egg. Then, the
      blastoderm cells move dynamically, retaining their positional information to form
      the posteriorly localized germ anlage. Furthermore, we find that the anterior
      head region of the cricket embryo is specified by orthodenticle in a cellular
      environment earlier than the gnathal and thoracic regions. Our findings imply
      that the syncytial mode of the early segmentation in long-germ insects evolved
      from a dynamic syncytial-to-cellular mode found in the present study, accompanied
      by a heterochronic shift of gap gene action.

PMID- 20800489
TI  - The effect of cane use method on center of mass displacement during stair ascent.
AB  - The aim of the study was to examine the effect of forward and lateral cane
      placement on displacement of whole body center of mass (COM) and spatial
      relationship between COM and the cane during stair ascent (SA) in healthy adults.
      The data were obtained using three-dimensional motion analysis while ascending
      stairs non-reciprocally with following methods: (1) dominant foot stepped up
      first, then the opposite foot without a cane (NC); (2) forward placement of a
      quadricane followed by the ipsilateral foot, then contralateral foot (FCI); (3)
      forward cane placement followed by the contralateral foot, then ipsilateral foot
      (FCC); (4) ipsilateral foot stepping up first, followed by the contralateral
      foot, then the cane (LCI); (5) contralateral foot stepping up, followed by the
      ipsilateral foot, then the cane (LCC). The results indicated that the cane
      placement had significant effect on the medial-lateral (ML) COM displacement and
      the kinematics of the trunk. Lateral cane placement requires greater trunk
      extension and side-flexion. The major differences between ipsilateral and
      contralateral cane use are the motions at frontal and transverse planes in which
      the COM displacement in ML direction is larger in ipsilateral cane use. The COM
      displacement in ML direction is larger in ipsilateral use of cane (LCI and FCI).
      The results of this study may help clinicians better understand the possible
      nature of balance control in patients who ascend stairs with a cane, and suggest
      that the method of cane placement should be taken into consideration by
      clinicians when teaching the cane user to ascend stairs.

PMID- 20800490
TI  - Neuronal ceroid lipofuscinosis diagnosed via skin biopsy.
AB  - We aim to report that skin biopsy, a non-invasive test by neurological standards,
      may lead to a diagnosis. A 4-year-old male presented with a 2-year history of
      epilepsy and progressive developmental regression. The patient had a mildly
      elevated ammonia level; however, evaluation for the accumulation of excess serum
      amino acids and evaluation of urine for organic acids was negative. MRI revealed
      cerebral atrophy, and an electroencephalogram demonstrated multifocal sharp and
      slow waves. Due to the progressive degenerative neurologic presentation, a
      neurologic storage disease was favored. An axillary skin biopsy was performed,
      revealing eosinophilic intra-cytoplasmic inclusions within the eccrine glands. A
      periodic acid-Schiff stain also highlighted these inclusions. Electron
      microscopic studies demonstrated characteristic multiple membrane-bound
      inclusions within the eccrine epithelial cells, containing curvilinear inclusion
      material characteristic of neuronal ceroid lipofuscinosis. The clinical,
      histological, electron microscopic and enzymatic studies were diagnostic of late
      infantile onset neuronal ceroid lipofuscinosis.

PMID- 20800491
TI  - Comparison of outpatient and inpatient spine surgery patients with regards to
      obesity, comorbidities and readmission for infection.
AB  - Outpatient spine surgery is becoming popular because of its substantial economic
      advantages. We retrospectively studied 97 spine surgery outpatients and 578
      inpatients who had proceeded through a common process of surgical venue
      selection. No differences (p > 0.05) were found in gender, race, obesity rate
      (46.9% versus [vs.] 42.9%), hypertension (9.7% vs. 8.8%), chronic obstructive
      pulmonary disease (11.8% vs. 13.5%), and history of stroke (1.9% vs. 2.5%).
      However, age was statistically different between inpatients (55 years) and
      outpatients (49 years) (p < 0.001). The prevalence of diabetes mellitus (19% vs.
      10%), congestive heart disease (19.7% vs. 1.3%), coronary artery procedures
      (15.9% vs. 3.8%), and use of antidepressants (25.4% vs. 11.6%) was higher in the
      inpatient group (p < 0.05). There were more comorbidities in the inpatient cohort
      of each spine surgery type except for chronic obstructive pulmonary disease
      (COPD) and history of stroke in the outpatient cervical surgery group (p < 0.05).
      Among outpatients, only one patient (~ 1%) had postoperative infection while
      among the inpatients, 16 patients had postoperative infections (2.8%) (p > 0.05).
      All seven patients readmitted due to infection were obese (body mass index >=
      30). Obese patients in the inpatient cohort had higher chronic disease rates.
      Comorbidities are the main determinants of inpatient/outpatient selection.
      Postoperative infection was not a significant complication for appropriately
      selected patients for outpatient spine surgery. Despite increased hospital care
      and observation in the inpatient group, infection rates were not statistically
      different. Obesity seems to be a predictor of readmission with infection.

PMID- 20800492
TI  - Successful treatment of sellar aspergillus abscess.
AB  - A sellar aspergillus abscess is a rare fungal infection of the central nervous
      system (CNS). A retrospective analysis of three patients with sellar aspergillus
      abscess was conducted from 2006 to 2008. Data were retrieved from patient records
      at our hospital. Clinical findings, pathological data and final outcomes were
      reviewed and analysed. All patients underwent transsphenoidal surgery with the
      operating microscope and histopathologic examination revealed aspergillosis in
      all cases. Postoperatively, all patients received medical treatment with
      voriconazole and caspofungin. During the 3-6-month follow-up period, the patients
      were symptom free with no recurrences. Therefore, sellar aspergillus abscess
      should be included in the differential diagnosis of a sellar mass. Early and
      correct diagnosis via surgery can improve the prognosis. A combination of
      surgical resection and antifungal therapy has a good outcome. The importance of
      early treatment for sellar aspergillus abscesses is emphasised.

PMID- 20800493
TI  - Intracranial hypertension caused by a meningioma compressing the transverse
      sinus.
AB  - We report a 55-year-old woman with intracranial hypertension due to unilateral
      extrinsic compression of the left transverse sinus by a meningioma. Because of
      the high risk of the conventional neurosurgical intervention, she underwent an
      endovascular procedure consisting of a transstenotic stent placement in the left
      transverse sinus. One month after stenting, her ophthalmological examination
      revealed complete regression of the bilateral papilledema, with persistent
      improvement at 1 year. Cerebral venous-stenting could be a safe alternative for
      patients suffering from intracranial hypertension caused by extrinsic sinus
      compression.

PMID- 20800494
TI  - Atlantoaxial stabilization utilizing atlas translaminar fixation.
AB  - Atlantoaxial instability is a potentially devastating sequela of tumor invasion
      to the upper cervical spine. We aim to report an alternative technique for
      atlantoaxial stabilization. Stabilization is technically demanding due to limited
      bony elements and proximity of the regional neurovascular structures. While the
      C1 lateral masses are considered robust points of fixation, one or both of these
      structures may be destroyed by pathology. A 54-year-old female presented with a
      lytic, metastatic lesion to one of the C1 lateral masses, which precluded its use
      for fixation. We utilized the contralateral hemilamina of the atlas for screw
      fixation and devised a stable construct that provided immediate stability. Thus,
      atlas translaminar fixation is a feasible option when the lateral masses cannot
      be utilized.

PMID- 20800495
TI  - Use of transcranial Doppler ultrasonography and jugular oximetry to optimize
      hemodynamics during pediatric posterior fossa craniotomy.
AB  - We describe a 13-year-old child who developed inadvertent intraoperative cerebral
      oxygen desaturation attributed to empiric hyperventilation during posterior fossa
      craniotomy, diagnosed by jugular venous oximetry. Although restoration of
      normocapnia at age-appropriate mean arterial blood pressure improved jugular
      venous saturation (SjvO), it remained below acceptable values. Transcranial
      Doppler (TCD) ultrasonography-guided stepwise increase in mean arterial pressure
      led to a linear increase in the mean flow velocity of the middle cerebral artery
      and SjvO2 to desirable values. Intraoperative SjvO2 monitoring and TCD
      ultrasonography may be utilized together to individualize hemodynamic targets and
      ventilation parameters and maintain adequate cerebral oxygenation during
      paediatric craniotomies.

PMID- 20800496
TI  - Rhabdoid meningioma presenting with subependymal and diffuse meningeal
      involvement but no mass lesion.
AB  - Rhabdoid meningiomas are rare, aggressive tumours of the meninges that have a
      generally poor prognosis. We report a 49-year-old man with a background history
      of sarcoidosis who presented with nausea and vomiting. Imaging showed generalised
      leptomeningeal and subependymal enhancement suggestive of chronic meningitis. He
      had multiple lumbar punctures and a brain biopsy, none of which led to a
      pathological diagnosis. He died within months, and a postmortem examination was
      performed. At this stage, a diagnosis of rhabdoid meningioma was made. The
      clinical and radiological presentation of rhabdoid meningioma as a diffuse
      leptomeningeal process without a mass lesion is unique. All other published cases
      of rhabdoid meningioma have been of a discrete lesion. This highlights the
      importance of a tissue diagnosis in patients where the imaging is non-specific. A
      brief review of rhabdoid meningioma follows.

PMID- 20800497
TI  - Treatment of atypical meningioma.
AB  - The aim of this study was to review the outcome after multimodality therapy in
      atypical meningiomas using the 2000 World Health Organization (WHO)
      classification system, and to suggest a logical therapeutic approach. Between
      April 1997 and February 2008, 35 patients with atypical meningiomas were managed
      in our hospital. All surgical specimens were reviewed according to the 2000 WHO
      classification system. The median follow-up was 40 months (range: 6-97 months).
      Radical extirpation surgery (Simpson grade I) was performed in 11 (31%) patients,
      and there was no tumor recurrence for these patients. For patients who underwent
      incomplete resection, the median interval to recurrence was increased from 17
      months for surgery alone to 39 months for surgery with adjuvant radiation therapy
      (p=0.138). Age, MIB-l labeling index, and tumor location had no significant
      effect on either progression-free survival or overall survival. Atypical
      meningiomas are difficult to manage and have high recurrence and poor survival
      rates. In our series, complete resection of the tumor is a key determinant for a
      better outcome. Adjuvant radiation therapy is recommended if incomplete surgical
      excision is performed.

PMID- 20800498
TI  - Investigating meniscal symptoms in patients with knee osteoarthritis--is MRI an
      unnecessary investigation?
AB  - The aim of this study was to evaluate the relationship between radiographic knee
      osteoarthritis and the presence of a relevant meniscal tear detected on MRI in
      symptomatic patients over the age of 60. Seventy seven patients over the age of
      60 who had been investigated with a knee MRI over a 1-year period were
      identified. Sixty patients had a full set of data available for analysis. Their
      plain radiographs were blindly graded for osteoarthritis using the Kellgren
      Lawrence (K-L) scale. The indications for the MRI were subdivided into: meniscal
      symptoms, general knee pain and "other". These indications were correlated with
      the K-L grade and result of the MRI. Overall, 40% of patients with a K-L grade of
      0 had a meniscal tear compared to 89% of patients with a K-L score of 3, and 88%
      with a K-L score of 4. The indications for an MRI were grouped into meniscal
      symptoms (49), general pain (6) and other (5). In the group investigated for
      meniscal symptoms, the incidence of meniscal tears was 92% and 100% with a K-L
      grade of 3 and 4 respectively. This equated to a positive predictive value of 93%
      for K-L grade 3 and above, and 100% for K-L grade 4 alone. Given the
      predictability of the MRI findings in patients with significant osteoarthritis as
      well as meniscal symptoms, we conclude that this is an unnecessary investigation
      when used for this indication.

PMID- 20800499
TI  - Delayed intra-articular migration of the IntraFix outer sheath after anterior
      cruciate ligament reconstruction: a case report.
AB  - We describe a case of foreign body synovitis caused by delayed intra-articular
      migration of the outer sheath 5 months after anterior cruciate ligament (ACL)
      reconstruction with a quadrupled tibialis allograft tendon using the IntraFix
      device for tibial fixation. The postoperative course was unremarkable. At 5
      months after surgery, the patient experienced a sudden catching sensation and a
      slight pain without any obvious twisting or trauma. At 6 months after surgery,
      extension deficit was 20 degrees . At arthroscopy, intra-articular migration of
      the outer sheath from the tibial tunnel and reactive synovitis were observed. The
      outer sheath in the joint and the inner screw in the tibial tunnel were removed
      successfully. The ACL graft was well incorporated under good tension. Patient was
      able to return to her previous level of all daily activities with no further
      episodes of swelling. To our knowledge, described here is the only case of
      foreign body synovitis due to intra-articular migration of the unbroken sheath.

PMID- 20800500
TI  - Design and synthesis of de novo cytotoxic alkaloids by mimicking the bioactive
      conformation of paclitaxel.
AB  - Novel paclitaxel-mimicking alkaloids were designed and synthesized based on a
      bioactive conformation of paclitaxel, that is, REDOR-Taxol. The alkaloid 2
      bearing a 5-7-6 tricyclic scaffold mimics REDOR-Taxol best among the compounds
      designed and was found to be the most potent compound against several drug
      sensitive and drug-resistant human cancer cell lines. MD simulation study on the
      paclitaxel mimics 1 and 2 as well as REDOR-Taxol bound to the 1JFF tubulin
      structure was quite informative to evaluate the level of mimicking. The MD
      simulation study clearly distinguishes the 5-6-6 and 5-7-6 tricyclic scaffolds,
      and also shows substantial difference in the conformational stability of the
      tubulin-bound structures between 2 and REDOR-Taxol. The latter may account for
      the large difference in potency, and provides critical information for possible
      improvement in the future design of paclitaxel mimics.

PMID- 20800501
TI  - Synthesis and biological activities of new di- and trimeric quinoline
      derivatives.
AB  - The synthesis of non-peptidic helix mimetics based on a trimeric quinoline
      scaffold is described. The ability of these new compounds, as well as their
      synthetic dimeric intermediates, to bind to various members of the Bcl-2 protein
      anti-apoptotic group is also evaluated. The most interesting derivative of this
      new series (compound A) inhibited Bcl-x(L)/Bak, Bcl-x(L)/Bax and Bcl-x(L)/Bid
      interactions with IC(50) values around 25 MUM.

PMID- 20800502
TI  - Development of a plate-based scintillation proximity assay for the mycobacterial
      AftB enzyme involved in cell wall arabinan biosynthesis.
AB  - A number of mycobacterial arabinosyltransferases, such as the Emb proteins, AftA,
      AftB, AftC, and AftD have been characterized and implicated to be involved in the
      cell wall arabinan assembly. These arabinosyltransferases are essential for the
      viability of the organism and are logically valid targets for developing new anti
      tuberculosis agents. For instance, Ethambutol, a first line anti-tuberculosis
      drug, targets the Emb proteins involved in the formation of the arabinan of cell
      wall arabinogalactan. Among these arabinosyltransferases, the terminal beta-(1
      >2) arabinosyltransferase activity has been associated with AftB. The predicted
      topology of AftB in Mycobacterium tuberculosis has 10 N terminal transmembrane
      domains and a C terminal hydrophilic domain similar to the Emb proteins. It has a
      conserved GT-C motif and is difficult to express. In a cell free assay, synthetic
      disaccharide, alpha-D-Araf-(1->5)-alpha-D-Araf-octyl, has been used as a
      substrate to explore the function of AftB. In our work, the disaccharide was
      synthesized in its pentenylated and biotinylated form, and the enzymatic product
      formed was identified as the beta-(1->2) arabinofuranose adduct. When synthetic
      tri- and tetra-saccharides were used as substrates, a mixture of products
      containing both beta-(1->2) and alpha-(1->5) linkages were formed. Therefore, the
      biotinylated disaccharide was selected to develop a scintillation proximity
      assay.

PMID- 20800504
TI  - Investigation of activation cross sections of deuteron induced reactions on
      indium up to 40 MeV for production of a 113 Sn/113m In generator.
AB  - (113)Sn (115.09 d) is the parent nuclide of the (113)Sn/(113m)In generator
      system. (113m)In (99.476 min) is used in diagnostic nuclear medicine and as an
      Auger-electron emitter is a candidate for internal radiotherapy. Excitation
      functions of the (nat)In(d,x) (113 mg)Sn, (116 m)In, (ind115m)In, (114m)In,
      (ind113m)In, (cum111)In, (115g)Cd,(111m)Cd reactions were measured up to 40 MeV
      for the first time. The experimental results were compared with the curves
      calculated with the ALICE-D and EMPIRE-D theoretical model codes and curves given
      in the EAF-2007 and TENDL-2009 databases. Thick target yields, impurity levels
      and specific activities for the optimal energy range were deduced and compared
      with the same parameters of other charged particle production routes of (113)Sn.

PMID- 20800503
TI  - Folding, DNA recognition, and function of GIY-YIG endonucleases: crystal
      structures of R.Eco29kI.
AB  - The GIY-YIG endonuclease family comprises hundreds of diverse proteins and a
      multitude of functions; none have been visualized bound to DNA. The structure of
      the GIY-YIG restriction endonuclease R.Eco29kI has been solved both alone and
      bound to its target site. The protein displays a domain-swapped homodimeric
      structure with several extended surface loops encircling the DNA. Only three side
      chains from each protein subunit contact DNA bases, two directly and one via a
      bridging solvent molecule. Both tyrosine residues within the GIY-YIG motif are
      positioned in the catalytic center near a putative nucleophilic water; the
      remainder of the active site resembles the HNH endonuclease family. The structure
      illustrates how the GIY-YIG scaffold has been adapted for the highly specific
      recognition of a DNA restriction site, in contrast to nonspecific DNA cleavage by
      GIY-YIG domains in homing endonucleases or structure-specific cleavage by DNA
      repair enzymes such as UvrC.

PMID- 20800505
TI  - Editorial comment: Listen and watch me carefully. Later, you can try it on your
      own patients.

PMID- 20800506
TI  - Vitamin D, light and mental health.
AB  - Vitamin D receptors and vitamin D metabolizing enzymes are present in the central
      nervous system. Calcitriol (the active vitamin D hormone) affects numerous
      neurotransmitters and neurotrophic factors, relevant for mental disorders. In the
      case of depressive disorders, considerable evidence supports a role of suboptimal
      vitamin D levels. However, the data are not conclusive and further studies are
      necessary. Especially, the relative importance of the pineal-melatonin system
      versus the vitamin D-endocrine system for the pathogenesis of seasonal affective
      disorders is presently unresolved. Two diagnoses, schizophrenia and autism, have
      been hypothetically linked to developmental (prenatal) vitamin D deficiency,
      however, also in adult patients, low levels have been reported, supporting the
      notion that vitamin D deficiency may not only be a predisposing developmental
      factor but also relate to the adult patients' psychiatric state. Two cases are
      described, whose psychiatric improvement coincided with effective treatment of
      vitamin D deficiency.

PMID- 20800507
TI  - Th1 and Th2 cytokines in a self-healing primary pulmonary Aspergillus flavus
      infection in BALB/c mice.
AB  - Studies with non-immunocompromised mice have demonstrated that Aspergillus flavus
      is more virulent than almost all other Aspergillus species. However, the type of
      immune response this fungus induces in mammals has not been investigated
      thoroughly. The study was carried out to analyze the sequential pathogenesis of
      pulmonary A. flavus infection and the role of cytokines in host response in
      BALB/c mice. Two distinct phases were observed in mice: First, an intense rate of
      clearance of A. flavus occurred, most likely through recruited neutrophils and
      the resident alveolar macrophages with concurrent release of pro-inflammatory
      cytokines and second, fungal and cellular debris were cleaned by recruited
      monocytes, pro-inflammatory cytokine production rapidly decreased and infection
      self-healed. The pro-inflammatory cytokine IFN-gamma demonstrated an upward trend
      up to 24h PI followed by a steady decline. The titers of TNF-alpha (a pro
      inflammatory Th1 cytokine) were, however, inversely related to the titers of IL
      10 an anti-inflammatory Th2 cytokine. The anti-inflammatory cytokine IL-4 showed
      slightly decreasing trend between 12 and 48 h PI, beyond that it again reached to
      the titers observed at 6h PI. The infected mice produced signs of Th1 type
      response with self healing capabilities.

PMID- 20800508
TI  - Hemochromatosis genotypes and risk of iron overload--a meta-analysis.
AB  - PURPOSE: The incomplete phenotypic penetrance of high iron Fe genotypes in
      relation to hemochromatosis poses a practical problem in the interpretation of
      the genotyping results by clinicians. We carried out meta-analyses of the
      associations between hemochromatosis genotypes C282Y/C282Y, C282Y/H63D,
      C282Y/wild-type, H63D/H63D, H63D/wild-type, versus wild-type/wild-type and iron
      overload, both provisional (elevated serum iron markers) and documented (elevated
      serum iron markers associated with evidence of iron excess based on liver biopsy
      and/or quantitative phlebotomy). METHODS: After reviewing 3572 article titles and
      evaluating 92 articles in detail, odds ratios were pooled from 43 study
      populations (9986 cases and 25,492 controls) using a random-effects model.
      RESULTS: Homozygosity for either variant or compound heterozygosity was
      associated with both provisional and documented iron overload. Single
      heterozygosity conferred no risk for elevated hepatic iron index and/or
      mobilizable iron by quantitative phlebotomy. In patients with clinical hereditary
      hemochromatosis, no evidence of provisional and documented iron overload with
      transferrin saturation (TS) values greater than 55% was evidenced for C282Y and
      H63D single heterozygotes whereas documented iron overload including TS of 45% to
      50% was weakly associated with C282Y/wild-type genotype; H63D/H63D genotype was
      not associated with documented iron overload in patients with TS values of 45% to
      50%. CONCLUSIONS: The results, mainly from case-control studies, cannot
      necessarily be extrapolated to the general population.

PMID- 20800509
TI  - Direct observation of the human microcirculation during cardiopulmonary bypass:
      effects of pulsatile perfusion.
AB  - OBJECTIVES: Possible benefits of pulsatile perfusion during cardiopulmonary
      bypass often are attributed to enhanced microvascular flow. However, there is no
      evidence to support this in humans. Therefore, the authors assessed whether
      pulsatile perfusion alters human microvascular flow. DESIGN: A prospective,
      randomized observational crossover study. SETTING: A tertiary cardiothoracic
      surgery referral center. PARTICIPANTS: Sixteen patients undergoing routine
      cardiopulmonary bypass for cardiac surgery. INTERVENTIONS: All patients underwent
      both pulsatile and nonpulsatile perfusion in random order. MEASUREMENTS AND MAIN
      RESULTS: The authors used sidestream dark-field imaging to record video clips of
      the sublingual human microcirculation. Perfusion was started either in the
      pulsatile (n = 8) or the nonpulsatile mode. After 10 minutes, microvascular
      recordings were made. The perfusion mode was then switched, and after 10 minutes,
      new microvascular recordings were taken. The authors quantified pulsatile
      perfusion-generated surplus hemodynamic energy by calculating pulse pressure and
      energy-equivalent pressure. Microvascular analysis included determination of the
      perfused vessel density (mean +/- standard deviation). This did not differ
      between nonpulsatile and pulsatile perfusion (6.65 +/- 1.39 v 6.83 +/- 1.23 mm(
      1), p = 0.58, and 2.16 +/- 0.64 v 1.96 +/- 0.48 mm(-1), p = 0.20 for small and
      large microvessels, respectively, cutoff diameter = 20 MUm). Pulse pressure and
      energy-equivalent pressure was higher during pulsatile perfusion. However, there
      was no correlation between the difference in energy-equivalent pressure or pulse
      pressure and perfused vessel density (r = -0.43, p = 0.13, and r = -0.09, p =
      0.76, respectively). CONCLUSION: Pulsatile perfusion does not alter human
      microvascular perfusion using standard equipment in routine cardiac surgery.
      Changes in pulse pressure or energy-equivalent pressure bear no obvious
      relationship with microcirculatory parameters.

PMID- 20800510
TI  - Fixation of the glenoid component in total shoulder arthroplasty: what is "modern
      cementing technique?".

PMID- 20800511
TI  - Postoperative rupture of the anterolateral deltoid muscle following reverse total
      shoulder arthroplasty in patients who have undergone open rotator cuff repair.
AB  - BACKGROUND: Postoperative ruptures of the antero-lateral deltoid in patients with
      reverse total shoulder arthroplasty utilizing the delto-pectoral approach
      following failed mini-open or open rotator cuff repairs have not been reported in
      the English literature. The incidence of this complication is unknown. MATERIALS
      AND METHODS: A retrospective review of 199 patients who underwent reverse total
      shoulder arthroplasty utilizing a deltopectoral approach was performed. These
      procedures were performed by 2 surgeons in 2 hospitals. There were 3 patients who
      had postoperative rupture of the deltoid. These ruptures occurred without any
      history of trauma to the patient. In all 3 patients, past surgical history was
      significant for a rotator cuff repair utilizing a mini-open or mini-open modified
      to open approach. Successful repair of the deltoid was achieved using a
      transosseous suture repair in all 3 patients. RESULTS: At most current follow-up
      (all >12 months), average forward elevation was 120 degrees . A small residual
      anterior deltoid defect was present in all 3 patients, but pain was quantified as
      0-4 out of 10 and radiographs demonstrated satisfactory position of the reverse
      arthroplasty implants. CONCLUSION: Postoperative ruptures of the antero-lateral
      deltoid can occur in patients who have undergone reverse total shoulder
      arthroplasty, utilizing the delto-pectoral approach following failed mini-open or
      open rotator cuff repairs. A supero-lateral approach during reverse total
      shoulder arthroplasty could be useful in assessing and possibly reinforcing a
      deltoid origin previously damaged or repaired during mini-open or open rotator
      cuff repair.

PMID- 20800512
TI  - Dutasteride monotherapy in men with serologic relapse following radical therapy
      for adenocarcinoma of the prostate: a pilot study.
AB  - OBJECTIVE: The objective of this study was to assess the effect of dutasteride on
      serum prostate specific antigen (PSA) levels in men with serologic relapse
      following radical prostatectomy and/or radiation therapy for clinically localized
      adenocarcinoma of the prostate. METHODS: A prospective, single institution, IRB
      approved trial was conducted. Entry criteria required that all participants have
      serologic disease relapse only with serum PSA levels between 0.4 and 10.0 ng/ml.
      Enrolled participants were treated with 0.5 mg dutasteride daily. The primary
      endpoints were serum PSA level and clinical recurrence. The rate of durable
      decline in PSA was assessed according to the recommendations of the Prostate
      Specific Antigen Working Group. RESULTS: Thirty-five patients provided informed
      consent and participated in the present study. At a median follow-up duration of
      27 months (range, 4-42 months), 46% of enrolled men had a serum PSA decrease of
      greater than 10%, and 25% had a serum PSA decrease of greater than 50% (P <
      0.001). Pre-study PSA doubling time (PSADT) (>=12 months vs. <12 months), and
      Gleason score (<=6 vs. >=7) were associated with a better response to
      dutasteride, but only PSADT was statistically significant (P < 0.001). Thirty
      percent of patients experienced PSA progression (increase in serum PSA of greater
      than 50%). Two (6%) patients developed bone metastasis. No patient was removed
      from the study for drug-related toxicity. CONCLUSIONS: In the present pilot
      study, treatment with dutasteride resulted in a significant decrease in serum PSA
      in men with serologic relapse following radical treatment for adenocarcinoma of
      the prostate. These data appear to suggest that dutasteride may delay or prevent
      progression of prostate cancer in some men with biochemical relapse after radical
      therapy. These findings require confirmation in the setting of a larger, longer
      trial.

PMID- 20800513
TI  - Hypermethylation of E-cadherin, p16, p14, and RASSF1A genes in pathologically
      normal urothelium predict bladder recurrence of bladder cancer after
      transurethral resection.
AB  - OBJECTIVES: This study investigated the hypermethylation of E-cadherin, p16, p14,
      and RASSF1A in pathologically normal urothelium to predict recurrence of bladder
      cancer after transurethral resection. MATERIALS AND METHODS: Samples of bladder
      tumor and paired pathologically normal urothelium were obtained from 50 bladder
      cancer patients. The status of promoter hypermethylation in these four genes was
      investigated by methylation-specific polymerase chain reaction. The
      clinicopathologic data in these patients were also analyzed in order to evaluate
      the clinical implication of aberrant methylation in bladder cancer recurrence.
      RESULTS: Hypermethylation of E-cadherin (30%), p16 (16%), p14 (14%), and RASSF1A
      (36%) was detected in the pathologically normal urothelium samples. Promoter
      hypermethylation occurred frequently in both pathologically normal urothelium and
      tumor samples from bladder cancer patients, and increased with progression from
      normal to bladder cancer at E-cadherin (P = 0.067), p16 (P < 0.001), p14 (P =
      0.01), and RASSF1A (P = 0.01). No significant correlation was observed between
      hypermethylation in any genes and muscle/organ invasion and stage/grade, except
      p14. However, p14 hypermethylation in pathologically normal urothelium samples
      was associated with shorter recurrence-free interval (P = 0.019). CONCLUSIONS:
      p14 hypermethylation could be involved in early stage of bladder carcinogenesis,
      and p14 hypermethylation in pathologically normal urothelium samples should be
      considered a predictor of bladder cancer recurrence.

PMID- 20800514
TI  - Prostate specific antigen screening for prostate cancer: knowledge of, attitudes
      towards, and utilization among primary care physicians.
AB  - OBJECTIVE: Prostate specific antigen (PSA) screening for prostate cancer
      screening is not uniformly recommended by national organizations or primary care
      physicians (PCPs). Given this lack of consensus, we sought to identify patterns
      in physician knowledge of and attitudes towards PSA screening and to determine
      how these patterns along with patient and provider demographics influence PSA
      screening practices. METHODS: A self-administered questionnaire, which assessed
      provider's knowledge of prostate cancer, confidence in his/her knowledge, and PSA
      screening practices, was mailed to PCPs at an academic medical center.
      Frequencies of responses were summarized and 3 outcome variables (knowledge,
      confidence, and propensity to screen) were derived. Association of covariates
      with the outcome variables was determined using multivariable logistic
      regression. RESULTS: Eight-two (30.4%) physicians completed the survey; 98%
      identified African-American race as a prostate cancer risk factor, 42% identified
      digital rectal exam and PSA as the accepted screening method, and 59%
      underestimated the likelihood of prostate cancer in a man with a PSA level > 4
      ng/ml; 19% were confident in their knowledge of prostate cancer; 86% screened
      fewer than 60% of their male patients over 50. A knowledge score above the median
      was not associated with a higher propensity to screen (r = 0.06, P = 0.61).
      Confidence in one's knowledge was correlated with ordering PSA testing (r = 0.33,
      P < 0.01). Physician (e.g., ethnicity) and patient (e.g., request for PSA
      testing) related factors, as well as practice guidelines, particularly those of
      the US Preventative Services Task Force, influenced providers' decision to offer
      PSA screening. CONCLUSIONS: Respondents correctly identified prostate cancer risk
      factors but were less knowledgeable about prostate cancer screening tests and
      overall prostate cancer risk. Most respondents were not confident in their
      knowledge and did not screen men over 50. Multiple patient- and provider-specific
      factors influence the decision to offer or not offer PSA screening.

PMID- 20800515
TI  - Serum hepcidin but not prohepcidin may be an effective marker for anemia of
      inflammation (AI).
AB  - Anemia in cancer patients can result from a complex interaction of numerous
      factors including iron deficiency, inflammation, toxicity related to therapy and
      effect of cancer on the marrow. Determining effective anemia treatment can
      therefore be complex, requiring a combination of diagnostic tests. Research on
      iron metabolism has highlighted the importance of hepcidin and its potential role
      in development of anemia of inflammation (AI). Hepcidin is a peptide that
      controls iron flow, is induced by inflammation and is speculated to cause the
      sequestration of iron in patients with inflammation. In the present study, serum
      hepcidin concentration determined by LC-MS/MS was shown to correlate with
      inflammatory markers in patients with anemia of cancer (AoC). In the absence of a
      widely-available serum hepcidin detection assay, detection of prohepcidin using a
      commercial assay has been used for several years as a surrogate for measuring
      serum hepcidin concentration. Analysis of prohepcidin concentration did not
      reveal any correlation with hepcidin or with inflammatory markers in patient
      samples and our data suggest that prohepcidin may not be stable in serum.
      Algorithms to sub-classify AoC patients showed that hepcidin was strongly
      associated with the population subset with inflammation and without iron
      deficiency. Serum hepcidin concentrations may therefore be a good predictor of
      AI, useful in diagnosis of anemia etiology and in treatment determination.

PMID- 20800517
TI  - Are fungi important in veterinary medicine?

PMID- 20800516
TI  - The familial Parkinson's disease gene DJ-1 (PARK7) is expressed in red cells and
      plays a role in protection against oxidative damage.
AB  - The antioxidant enzyme manganese superoxide dismutase (SOD2) serves as the
      primary defense against mitochondrial superoxide. Impaired SOD2 activity in
      murine hematopoietic cells affects erythroid development, resulting in anemia
      characterized by intra-mitochondrial iron deposition, reticulocytosis and
      shortened red cell life span. Gene expression profiling of normal and SOD2
      deficient erythroblasts identified the Parkinson's disease locus DJ-1 (Park7) as
      a differentially expressed transcript. To investigate the role of DJ-1 in
      hematopoietic cell development and protection against oxidative stress caused by
      Sod2 loss, we evaluated red cell parameters, reticulocyte count, red cell
      turnover and reactive oxygen species production in DJ-1 knockout animals and
      chimeric animals lacking both SOD2 and DJ-1 in hematopoietic cells generated by
      fetal liver transplantation. We also investigated DJ-1 protein expression in
      primary murine erythroid and erythroleukemia cells (MEL). Loss of DJ-1
      exacerbates the phenotype of SOD2 deficiency, increasing reticulocyte count and
      decreasing red cell survival. Using MEL cells, we show that DJ-1 is up-regulated
      at the protein level during erythroid differentiation. These results indicate
      that DJ-1 plays a physiologic role in protection of erythroid cells from oxidant
      damage, a function unmasked in the context of oxidative stress.

PMID- 20800518
TI  - Recurrence of Chlamydiasuis infection in pigs after short-term antimicrobial
      treatment.
AB  - The effect of short-term antimicrobial treatment on natural excretion of
      Chlamydia suis in rectal swabs and C. suis and Chlamydophila psittaci in nasal
      swabs was investigated in 47 clinically normal piglets by quantitative real-time
      PCR. Pigs were treated IM with 4 mg/kg enrofloxacin for 5 days (n = 22) or
      2.5mg/kg enrofloxacin for 3 days followed by 100mg/mL tiamulin (n = 25).
      Antimicrobial treatment reduced the number of pigs positive for chlamydiae and
      the quantity of chlamydial DNA in positive swabs for a few days, but chlamydial
      excretion recurred in both groups. Short-term antimicrobial treatment at dosages
      recommended for treatment of other bacterial infections in pig herds was not
      effective in eliminating naturally occurring subclinical chlamydial infection in
      pigs.

PMID- 20800519
TI  - Self-reported quality of life has no correlation with functional status in
      children and adolescents with spinal muscular atrophy.
AB  - BACKGROUND: Spinal muscular atrophy is one of the most common neuromuscular
      disorders in children. Associated with progressive muscular weakness, it may
      assume a chronic course. In chronic disorders it is of utmost importance to
      determine the quality of life level. OBJECTIVE: To determine the level of quality
      of life in a cohort of SMA children and adolescents, and study its relation to
      motor ability. METHODS: From the children and adolescents with confirmed SMA
      diagnosis (presence of deletion) followed at a University Hospital, we selected
      those that were 4 years or older. They were classified as SMA type II or III
      according to their best motor ability, evaluated according to the modified
      Hammersmith functional score, and undertook the AUQEI Portuguese version to
      determine quality of life. This is an Institutional Review Board approved study
      and consent was given by all those included. RESULTS: Thirty-three children and
      adolescent with a mean age of 10.28 (+/- 4.71) took part of the study. The
      fourteen SMA type II had a mean Hammersmith score of 11 (+/- 9.50) and AUQEI of
      55.85 (+/- 7.16), while the nineteen SMA type III scored 31.10 (+/- 12.30) and
      52.94 (+/- 4.85). No significant difference was found when quality of life scores
      was compared among those groups. CONCLUSION: On a self-reported scale it seems
      that regardless the functional status an SMA child and adolescent has a
      perception of good quality of life.

PMID- 20800520
TI  - Calculation and application of activity discriminants in lead optimization.
AB  - We present a technique for computing activity discriminants of in vitro
      (pharmacological, DMPK, and safety) assays and the application to the prediction
      of in vitro activities of proposed synthetic targets during the lead optimization
      phase of drug discovery projects. This technique emulates how medicinal chemists
      perform SAR analysis and activity prediction. The activity discriminants that are
      functions of 6 commonly used medicinal chemistry descriptors can be interpreted
      easily by medicinal chemists. Further, visualization with Spotfire allows
      medicinal chemists to analyze how the query molecule is related to compounds
      tested previously, and to evaluate easily the relevance of the activity
      discriminants to the activities of the query molecule. Validation with all
      compounds synthesized and tested in AstraZeneca Wilmington since 2006
      demonstrates that this approach is useful for prioritizing new synthetic targets
      for synthesis.

PMID- 20800521
TI  - Tetrapyrrole binding affinity of the murine and human p22HBP heme-binding
      proteins.
AB  - We present the first systematic molecular modeling study of the binding
      properties of murine (mHBP) and human (hHBP) p22HBP protein (heme-binding
      protein) with four tetrapyrrole ring systems belonging to the heme biosynthetic
      pathway: iron protoporphyrin IX (HEMIN), protoporphyrin IX (PPIX), coproporphyrin
      III (CPIII), coproporphyrin I (CPI). The relative binding affinities predicted by
      our computational study were found to be similar to those observed
      experimentally, providing a first rational structural analysis of the molecular
      recognition mechanism, by p22HBP, toward a number of different tetrapyrrole
      ligands. To probe the structure of these p22HBP protein complexes, docking,
      molecular dynamics and MM-PBSA methodologies supported by experimental NMR ring
      current shift data have been employed. The tetrapyrroles studied were found to
      bind murine p22HBP with the following binding affinity order: HEMIN> PPIX> CPIII>
      CPI, which ranged from -22.2 to -6.1 kcal/mol. In general, the protein
      tetrapyrrole complexes are stabilized by non-bonded interactions between the
      tetrapyrrole propionate groups and basic residues of the protein, and by the
      preferential solvation of the complex compared to the unbound components.

PMID- 20800522
TI  - Considerations and recommendations for national guidance regarding the retention
      and use of residual dried blood spots specimens after newborn screening.

PMID- 20800523
TI  - Genetic, structural and biochemical basis of carbamoyl phosphate synthetase 1
      deficiency.
AB  - Carbamoyl phosphate synthetase 1 (CPS1) plays a paramount role in liver
      ureagenesis since it catalyzes the first and rate-limiting step of the urea
      cycle, the major pathway for nitrogen disposal in humans. CPS1 deficiency (CPS1D)
      is an autosomal recessive inborn error which leads to hyperammonemia due to
      mutations in the CPS1 gene, or is caused secondarily by lack of its allosteric
      activator NAG. Proteolytic, immunological and structural data indicate that human
      CPS1 resembles Escherichia coli CPS in structure, and a 3D model of CPS1 has been
      presented for elucidating the pathogenic role of missense mutations. Recent
      availability of CPS1 expression systems also can provide valuable tools for
      structure-function analysis and pathogenicity-testing of mutations in CPS1. In
      this paper, we provide a comprehensive compilation of clinical CPS1 mutations,
      and discuss how structural knowledge of CPS enzymes in combination with in vitro
      analyses can be a useful tool for diagnosis of CPS1D.

PMID- 20800524
TI  - Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI): a single dose of
      galsulfase further reduces urine glycosaminoglycans after hematopoietic stem cell
      transplantation.
AB  - BACKGROUND: Maroteaux-Lamy syndrome, or mucopolysaccharidosis (MPS) type VI, is
      the autosomal recessive lysosomal disorder resulting from deficient N
      acetylgalactosamine 4-sulfatase (ARSB) and the consequent accumulation of
      glycosaminoglycan (GAG). Patients fully engrafted after hematopoietic stem cell
      transplantation (HSCT) demonstrate several indicators of metabolic correction
      such as reduction in liver size, absence of hepatic ultrastructural pathology,
      and patients do not develop cervical cord compression. Engrafted patients
      demonstrate reduction in urine GAG achieving near-normal levels. HYPOTHESIS: We
      presumed that HSCT engraftment from a normal individual would provide sufficient
      systemic enzyme to accomplish maximal metabolic correction, and that no
      additional benefit would accrue from additional therapy such as with intravenous
      recombinant human ARSB protein, galsulfase. MATERIALS AND METHODS: A 22-year-old
      male had received an allogeneic bone marrow transplant from an HLA-identical
      sibling donor, and remained fully engrafted after 20 years. In response to his
      request regarding the potential benefit of enzyme replacement therapy, we
      administered a single, standard dose of galsulfase while monitoring urine GAG
      daily, before and after the treatment. RESULTS: Urine GAG declined from slightly
      high pre-treatment levels (7.63 mg GAG/mmol creatinine; range 7.0-8.5, N=3)
      progressively declining below the age-specific normal range (<6.5) over 10 days
      to the lowest level of 4.4, with a mean post-treatment level of 5.60 (N=10).
      CONCLUSIONS: Somewhat surprisingly, the biomarker urine GAG was significantly
      reduced after a single treatment of intravenous galsulfase thus suggesting that
      supplemental enzyme replacement therapy might improve the clinical outcome for
      donor-engrafted patients with MPS VI.

PMID- 20800525
TI  - Health-seeking patterns among participants of population-based morbidity
      surveillance in rural western Kenya: implications for calculating disease rates.
AB  - BACKGROUND: Calculation of disease rates in developing countries using facility
      based surveillance is affected by patterns of health utilization. We describe
      temporal patterns in health care seeking by syndrome as part of population-based
      morbidity surveillance in rural western Kenya. METHODS: From July 2006 to June
      2008, health utilization data were collected from 27 171 participants at biweekly
      home visits and at Lwak Hospital, the designated referral clinic where free care
      provided by dedicated study clinical staff was available. Ill persons were asked
      if and where they sought care. Proportions seeking care for children and adults
      with fever, acute respiratory infection (ARI), acute lower respiratory infection
      (ALRI), and diarrhea were compared by Chi-square test. Care-seeking by distance
      was evaluated by logistic regression. RESULTS: While care-seeking outside the
      home was common for all syndromes (>50%), only 18-38% of care-seeking was to
      health facilities. Children were more likely than adults to visit health
      facilities for all syndromes. Of ill persons visiting Lwak Hospital, 45-54% had
      previously sought care elsewhere, mostly from informal drug sellers, and 11-24%
      with fever, ARI, or ALRI had already taken an antimalarial or antibiotic. The
      distance from the participant's home to Lwak Hospital was the most common reason
      (71%) for ill participants not seeking care there. The likelihood of visiting
      Lwak decreased with increasing distance of residence (p<0.001) and fluctuated
      significantly over the study period. CONCLUSIONS: Even in a study setting where
      free and reliable care is offered, health utilization is affected by other
      factors, such as distance. Health utilization data in population-based
      surveillance are important in adjusting disease rates.

PMID- 20800526
TI  - Osteomyelitis in adults: an underrecognized clinical entity in immunocompetent
      hosts. A report of six cases.
AB  - OBJECTIVE: Osteomyelitis is rare in adults and typically occurs in patients with
      risk factors such as sickle cell disease or immune deficiency. Cases in
      immunocompetent adults without sickle cell disease are extremely rare. The
      objective of this work was to describe the epidemiological, clinical, laboratory,
      and radiological features and the management of long-bone osteomyelitis in
      immunocompetent adults without sickle cell disease. METHODS: We conducted a
      retrospective descriptive study of all immunocompetent adults without sickle cell
      disease who were admitted to our center between November 2002 and November 2008
      for long-bone osteomyelitis. In all patients, the clinical symptoms started in
      adulthood, in the absence of a childhood history of osteomyelitis. RESULTS: We
      identified six patients meeting our inclusion criteria over the 6-year study
      period. The causative microorganism was methicillin-susceptible Staphylococcus
      aureus in four patients and Salmonella in two patients (wild-type S. typhi and S.
      enterica, respectively). In each patient, there was a single focus of
      osteomyelitis and a single causative microorganism. The symptoms developed
      insidiously and lacked specificity. At presentation, the patients had moderate
      pain with or without a swelling. There was no fever initially in five patients,
      three of whom had major diagnostic delays as a result. Treatment associated
      antibiotics and surgery in all patients and the initial outcome was consistently
      favorable (median follow-up: 15 months; range: 8-72). CONCLUSION: Osteomyelitis
      can occur even in immunocompetent adults. The protracted course and atypical
      presentation of osteomyelitis in immunocompetent adults may lead to major
      diagnostic delays.

PMID- 20800527
TI  - [Closed carrier device: a reality to vitrify oocytes and embryos in aseptic
      conditions].
AB  - Vitrification with the use of "Open" carrier devices (Cryoloop, cryotop,
      cryoleaf, Vitriplug) which allowed the contact with liquid nitrogen has become a
      more popular way to achieve cooling rate superior to 20,000  degrees C/min. Even
      though the question of contamination with liquid nitrogen during ultra-rapid
      cooling and storage remain debatable with the use of "open" devices, it is
      important to revise the carrier system in a way, which minimizes the risk of
      contamination. According to the EU tissues and cells directive, it is advisable
      that the cooling and storage should be carried out in embryo carrier devices
      ensuring complete separation of the embryos from liquid nitrogen in a way, which
      minimizes the risk of contamination. The consequence of a reduction in the
      cooling rate resulting from the heat-insulating barrier of aseptic devices has to
      be counteracted by gradually increasing intracellular concentrations of
      cryoprotectants without inducing a toxic effect. We developed an aseptic
      vitrification method of vitrification for MII oocytes and embryos at different
      stage of development using the "VitriSafe" as "closed" carrier device.

PMID- 20800528
TI  - [Vitrification and the use of high concentrations of cryoprotectants: is it a
      justified argument to prefer slow freezing?].
AB  - The use of high levels of cryoprotectants (CPs) in solutions applied to vitrify
      oocytes or embryos is an argument to still prefer slow freezing procedure. Is it
      a justified argument? Out of three studies using mice zygotes we may assume that
      (i) the intracellular concentration of CPs is far lower than the one in the
      vitrification solutions, (ii) the intracellular concentration of CPs in the
      vitrified zygote is in contrary to the common beliefs even lower than the one
      observed after a slow freezing procedure, (iii) survival after slow freezing
      reflects the presence of an intracellular vitrified state in these cells.

PMID- 20800529
TI  - Frequency effects on the sonochemical degradation of chlorinated compounds.
AB  - The effects of frequency in chlorobenzene, chloroform, and carbon tetrachloride
      have been experimentally investigated in this study. The irradiation frequencies
      were 35, 74, 170, 300 and 1000 kHz. The degradation rates of chlorobenzene,
      chloroform, and carbon tetrachloride were highest at 300 kHz. The results of
      between formation of hydrogen peroxide concentration and degradation of
      chlorinated compounds were not a coincidence. Methods of the sonochemical
      efficiency were needed to review. The concentration of total organic carbon was
      remained after 4 h of sonication. High power intensity, longer sonication time,
      addition of catalysts and combination of the AOP process, were needed for the
      degradation of TOC. The formation of chloride ion in aqueous solution was evident
      for the degradation of chlorinated compounds. However, the theoretical
      concentration of chloride ion was higher than the measured concentration. This
      means that the remaining chlorinated contaminants in each solution cannot
      complete dechlorination and some intermediated were produced.

PMID- 20800530
TI  - Large SGCE deletion contributes to Taiwanese myoclonus-dystonia syndrome.
AB  - We report three novel deletions of the SGCE gene in three families with myoclonus
      dystonia (M-D) syndrome in Taiwan. Their clinical characteristics included: early
      onset, dominant myoclonus and dystonia in the neck, trunk and upper limbs. By
      direct sequencing of the SGCE gene coding regions, we identified a small
      heterozygous deletion (c.842delA) in exon 7 of the three sibs and asymptomatic
      father in the first family and an eight-base heterozygous deletion (c.524_531del)
      in exon 5 of the mother and a daughter in the second family. Using multiple
      ligation-dependent probe amplification (MLPA), a large heterozygous deletion of 2
      11 exons was identified in the father and a son in the third family which was
      undetected by initial sequencing. It is the largest intragenic deletion ever
      reported. In conclusion, we have identified three novel mutations of SGCE in the
      respective three M-D families. The large deletion was responsible for one third
      of these M-D families which might implicate an important contribution to
      Taiwanese M-D syndrome. We suggest that the contribution of large deletion should
      be further verified in a large cohort of patients with M-D syndrome in Han
      Chinese.

PMID- 20800531
TI  - Botulinum toxin for painful limbs moving extremities: are distal injections
      critical?

PMID- 20800532
TI  - Race, class and the stigma of place: moving to "opportunity" in Eastern Iowa.
AB  - In this paper, we explore how the stigmatization of place is transported to new
      destinations and negotiated by those who carry it. Additionally, we discuss the
      implications of 'spatial stigmatization' for the health and well-being of those
      who relocate from discursively condemned places such as high-poverty urban
      neighborhoods. Specifically, we analyze in-depth interviews conducted with 25 low
      income African American men and women who have moved from urban neighborhoods in
      Chicago to predominantly white small town communities in eastern Iowa. These men
      and women, who moved to Iowa in the context of gentrification and public housing
      demolition, describe encountering pervasive stigmatization that is associated not
      only with race and class, but also with defamed notions of Chicago neighborhoods.

PMID- 20800533
TI  - Genomic insights into photosynthesis in eukaryotic phytoplankton.
AB  - The evolution of photosynthesis completely altered the biogeochemistry of our
      planet and permitted the evolution of more complex multicellular organisms.
      Curiously, terrestrial photosynthesis is carried out largely by green algae and
      their descendents the higher plants, whereas in the ocean the most abundant
      photosynthetic eukaryotes are microscopic and have red algal affiliations.
      Although primary productivity is approximately equal between the land and the
      ocean, the marine microbes represent less than 1% of the photosynthetic biomass
      found on land. This review focuses on this highly successful and diverse group of
      organisms collectively known as phytoplankton and reviews how insights from whole
      genome analyses have improved our understanding of the novel innovations employed
      by them to maximize photosynthetic efficiency in variable light environments.

PMID- 20800534
TI  - Geometrical analysis of registration errors in point-based rigid-body
      registration using invariants.
AB  - Point-based rigid registration is the method of choice for aligning medical
      datasets in diagnostic and image-guided surgery systems. The most clinically
      relevant localization error measure is the Target Registration Error (TRE), which
      is the distance between the image-defined target and the corresponding target
      defined on another image or on the physical anatomy after registration. The TRE
      directly depends on the Fiducial Localization Error (FLE), which is the
      discrepancy between the selected and the actual (unknown) fiducial locations.
      Since the actual locations of targets usually cannot be measured after
      registration, the TRE is often estimated by the Fiducial Registration Error
      (FRE), which is the RMS distance between the fiducials in both datasets after
      registration, or with Fitzpatrick's TRE (FTRE) formula. However, low FRE-TRE and
      FTRE-TRE correlations have been reported in clinical practice and in theoretical
      studies. In this article, we show that for realistic FLE classes, the TRE and the
      FRE are uncorrelated, regardless of the target location and the number of
      fiducials and their configuration, and regardless of the FLE magnitude
      distribution. We use a geometrical approach and classical invariant theory to
      model the FLE and derive its relation to the TRE and FRE values. We show that,
      for these FLE classes, the FTRE and TRE are also uncorrelated. Finally, we show
      with simulations on clinical data that the FRE-TRE correlation is low also in the
      neighborhood of the FLE-FRE invariant classes. Consequently, and contrary to
      common practice, the FRE and FTRE may not always be used as surrogates for the
      TRE.

PMID- 20800535
TI  - Microfluidic landscapes for evolution.
AB  - Evolution at its heart is an iterative algorithm composed of three steps:
      selection, amplification and mutagenesis. This algorithm can be applied to
      complex inputs such as populations of whole organisms and viruses, or mixtures of
      bare nucleic acids and proteins. The output is the same: evolutionary adaptation
      of new and improved function subject to selection. Recent breakthroughs in
      microfluidic technology have introduced automation and process monitoring to in
      vitro evolution, and reproducible preparation of emulsions and other multi-phase
      reaction landscapes. It is at this intersection of compartmentalization and in
      vitro evolution where miniaturization is again redefining experimental design in
      contemporary chemistry and biology.

PMID- 20800536
TI  - Rapid green synthesis of spherical gold nanoparticles using Mangifera indica
      leaf.
AB  - This paper reports the rapid biological synthesis of spherical gold nanoparticles
      at room temperature using fresh/dry leaf extract of Mangifera indica. This is a
      simple, cost-effective, stable for long time and reproducible aqueous synthesis
      method to obtain a self-assembly of nearly monodispersed Au nanoparticles of size
      ~20 nm and 17 nm. The nanoparticles were obtained within 2 min of addition of the
      extract to the solution of HAuCl 4.3H2O and the colloid is found to be stable for
      more than 5 months. Smaller and more uniformly distributed particles could be
      obtained with dried leaf extract. The nanoparticles obtained are characterized by
      UV-vis, transmission electron microscopy (TEM) and X-ray diffraction (XRD).
      Crystalline nature of the nanoparticles in the fcc structure is confirmed by the
      peaks in the XRD pattern corresponding to (111), (200), (220), (311) and (222)
      planes, bright circular spots in the selected area electron diffraction (SAED)
      and clear lattice fringes in the high-resolution TEM image. The possible
      biomolecules responsible for efficient stabilization are suggested by studying
      the FTIR spectrum of the sample. This environmentally benign method provides much
      faster synthesis and colloidal stability comparable to those of chemical
      reduction.

PMID- 20800538
TI  - Movement imagery-related lateralization of event-related (de)synchronization
      (ERD/ERS): motor-imagery duration effects.
AB  - OBJECTIVE: To investigate movement imagery-related lateralization of event
      related (de)synchronization (ERD/ERS) during two motor-imagery tasks with varying
      movement duration (brief versus continuous). METHODS: Twelve subjects performed
      or kinesthetically imagined the indicated movement (left or right hand movement)
      for 1 s (brief) or 5 s (continuous) while electroencephalograms (EEGs) were
      recorded using 16 electrodes covering the sensorimotor cortex of the brain
      according to the modified 10-20 system. RESULTS: Significant hemispheric
      differences were found between contralateral and ipsilateral area in mu ERD, mu
      ERS and beta ERD during both brief and continuous conditions, showing
      contralateral dominance of mu and beta ERD and ipsilateral dominance of mu ERS.
      Beta ERS showed a significant ipsilateral dominance only in the brief condition.
      Movement imagery duration influenced the lateralization of mu ERD, beta ERD, and
      beta ERS, but not mu ERS. CONCLUSIONS: The results of this study will aid in
      clarifying movement-related lateralization in association with imagery tasks
      under varying movement duration. SIGNIFICANCE: For designing an EEG-based brain
      computer interface (BCI) for people with severe neuromuscular impairments,
      movement imagery-related lateralization can play a key role in utilizing motor
      imagery tasks as a control or communication strategy.

PMID- 20800537
TI  - Effect of KI/AgI on the thermal and optical properties of the GeS2-In2S3
      chalcogenide glasses.
AB  - GeS2-In2S3-KI/AgI chalcohalide glasses were prepared by traditional melt
      quenching method and the glass-forming region was determined. The dependence of
      glass properties on composition as formula of (100 - x)(0.75GeS2-0.25In2S3) -
      x(In2S3-KI/AgI) was investigated. The allowed indirect transition of samples was
      calculated according to the classical Tauc equation. The results show that 50
      mol% AgI can be introduced in the glassy matrix while only 40 mol% of KI can be
      incorporated in the GeS2-In2S3-KI glass system. GeS2-In2 S3-AgI glass system has
      larger density, higher refractive index and better thermal stability, while GeS2
      In2S3-KI glass system has shorter visible cut-off wavelength and higher optical
      band gap.

PMID- 20800539
TI  - Effects of unilateral voluntary movement on motor imagery of the contralateral
      limb.
AB  - OBJECTIVE: To investigate whether unilateral voluntary movement affects voluntary
      drive of motor imagery for the contralateral limb. METHODS: The subjects were
      asked to maintain the left index-finger movements with different directions
      (abduction and adduction, 5% of maximum voluntary contraction; MVC) and with
      different force levels (10% and 25% MVC). Under these conditions, transcranial
      magnetic stimulation was applied over the left motor cortex to record motor
      evoked potential (MEP) from the right first dorsal interosseous muscle with or
      without motor imagery of the right index-finger abduction. RESULTS: Voluntary
      movement of the left index finger with isodirection, but not mirrored direction,
      to the imagined movement reduced the MEP enhancement induced by motor imagery.
      MEP was gradually increased depending on increment of the force level on the left
      side, while the motor imagery-induced MEP enhancement was consequently reduced.
      CONCLUSIONS: Enhancement of the motor cortex excitability driven by motor imagery
      of the contralateral limb is interfered with by isodirection and forceful
      movement of the ipsilateral limb, which may be due to an increase in the
      transcallosal inhibitory effects. SIGNIFICANCE: Using motor imagery as a
      therapeutic tool, the voluntary movements on the other side of the body should be
      taken into account.

PMID- 20800540
TI  - Identifying key belief-based targets for promoting regular physical activity
      among mothers and fathers with young children.
AB  - We investigated the key beliefs to target in interventions aimed at increasing
      physical activity (PA) among mothers and fathers of young children. Parents (288
      mothers and 292 fathers) completed a Theory of Planned Behaviour belief-based
      questionnaire and a 1-week follow-up of PA behaviour. We found that a range of
      behavioural, normative, and control beliefs were significantly correlated with
      parents' PA intentions and behaviour, with only a few differences observed in
      correlations between PA beliefs and intention and behaviour by gender. A range of
      key beliefs was identified as making independent contributions to parents' PA
      intentions; however, the behavioural beliefs about improving parenting practices
      (beta=0.13), interfering with other commitments (beta=-0.29); normative beliefs
      about people I exercise with (beta=0.20); and control beliefs about lack of time
      (beta=-0.24), inconvenience (beta=-0.14), lack of motivation (beta=-0.34), were
      revealed as significant independent predictors of actual PA behaviour.
      Furthermore, we found that a limited amount of parents already hold these
      beliefs, suggesting that these key beliefs warrant changing and, therefore, are
      appropriate targets for subsequent intervention. The current study fills an
      empirical gap in the PA literature by investigating an at-risk group and using a
      well established theoretical framework to identify key beliefs that guide
      parents' PA decision-making. Overall, we found support for parents being a unique
      group who hold distinctive behavioural, normative, and control beliefs toward PA.
      Attention to these key underlying beliefs will assist intervention work aimed at
      combating inactivity among this at-risk population.

PMID- 20800541
TI  - Endovascular covered stent treatment for descending aorta pseudoaneurysm
      following coarctation of the aorta repair in an infant.
AB  - The development of a pseudoaneurysm is a rare complication following repair of a
      coarctation of the aorta. Surgical management of pseudoaneurysms is associated
      with high morbidity and mortality. We describe the successful endovascular
      deployment of a covered stent in a sick infant with a descending aorta
      pseudoaneurysm, following the repair of an aortic coarctation. We highlight the
      challenges we encountered. Endovascular repair is a safe palliative alternative
      to re-do open surgery in unstable infants with large pseudoaneurysms following
      aortic coarctation repair. The role of endovascular stents as the final
      definitive therapy will remain limited by the deployable, small-size stents in
      small, growing children.

PMID- 20800542
TI  - Effect of statins in preventing postoperative atrial fibrillation following
      cardiac surgery.
AB  - BACKGROUND: Postoperative occurrence of AF has been associated with less
      favourable outcomes in patients undergoing cardiac surgery and may result in
      increased postoperative morbidity and mortality. OBJECTIVES: A focused clinical
      question was designed and a meta-analysis of published studies was performed to
      identify the effect of preoperative use of statins on the occurrence of AF after
      cardiac surgery. METHODS: Using the Medline database, the Cochrane clinical
      trials database and online clinical trial databases, we reviewed all RCTs and
      observational studies examining the effect of statins on AF occurrence following
      cardiac surgery. We searched for the literature published before April 2009 and
      earlier. RESULTS: This analysis identified six studies (observational studies)
      which examined the effect of preoperative use of statins on AF occurrence
      following cardiac surgery, involving 10,165 patients. Contradictory to most of
      previous studies, the overall outcomes suggested that the statins group did not
      have a significant decrease in AF occurrence following cardiac surgery comparing
      to control group (P=0.19). CONCLUSIONS: The preoperative medication of statins
      showed no significant decrease in AF occurrence following cardiac surgery in this
      meta-analysis result. More prospective studies and researches are needed to
      explore and demonstrate the accurate mechanism and effect of statins on
      postoperative AF.

PMID- 20800543
TI  - Choosing anti-Plasmodium molecules for genetically modifying mosquitoes: focus on
      peptides.
AB  - In the wake of the development of insecticide resistance in mosquitoes, novel
      strategies for halting malaria transmission are being developed. These include
      the genetic modification (GM) of mosquitoes to become incompetent vectors.
      Although mosquito GM technologies are progressing rapidly, the rationale behind
      choosing anti-parasite molecules to be expressed by mosquitoes has received less
      attention. Here, questions are explored that that should be addressed during the
      strategic selection of these anti-Plasmodium molecules, focusing on antimicrobial
      peptides. Properties that will enhance the likelihood of success are discussed,
      and the need to plan an initial strategy to eliminate molecules that cause
      fitness costs to the mosquito is considered. Effector molecules with proven anti
      sporogonic stage activity are reviewed, and the activity of a selection of these
      molecules is detailed.

PMID- 20800544
TI  - Implication of apoptosis in sperm cryoinjury.
AB  - Apoptosis is an ongoing physiological phenomenon that has been documented to play
      a role in male infertility, if deregulated. Caspase activation, externalization
      of phosphatidylserine, alteration of mitochondrial membrane potential and DNA
      fragmentation are markers of apoptosis found in ejaculated human spermatozoa.
      These markers appear in excess in subfertile men and functionally incompetent
      spermatozoa. Sperm cryopreservation is a widely used procedure in the context of
      assisted reproductive techniques. Cryopreservation and thawing is a procedure
      that inflicts irreversible injury on human spermatozoa. The damage is manifested
      by a decrease in recovery of viable spermatozoa with optimum fertilization
      potential. This review describes the implication of apoptosis as one of the
      possible mechanisms involved in sperm cryoinjury. Evidence shows significant
      increase in some apoptosis markers following cryopreservation and thawing. On the
      other hand, the increase in sperm DNA fragmentation following cryopreservation
      and thawing requires further investigation. Specific technical measures should be
      applied to minimize the induction of apoptosis in human spermatozoa during
      cryopreservation and thawing. These include standardization of freezing protocols
      and cryoprotectant use. Selection of non-apoptotic spermatozoa may also prove to
      be of benefit.

PMID- 20800545
TI  - Misplaced obsession with prospectively randomized studies.
AB  - Medical care should be based on best available evidence. While randomized
      controlled trials (RCT) are currently considered a gold standard of study design,
      they are not always available and do not represent the only study format that can
      lead to best available evidence. This communication argues that overvaluation of
      RCT and undervaluation of other study formats in establishing best available
      evidence hurts progress in reproductive medicine and in medicine in general.

PMID- 20800546
TI  - Can Doppler ultrasound-guided oocyte retrieval improve IVF safety?
AB  - Transvaginal ultrasound-guided oocyte retrieval has gained universal acceptance
      with an excellent safety record overall. However, even with contemporary
      ultrasound resolution, the aspiration needle can injure adjacent pelvic organs
      and blood vessels and result in external and internal bleeding. Although the idea
      that Doppler ultrasound might reduce the risk of blood vessel injury during
      follicular aspiration seems to be plausable, measurement of peritoneal blood loss
      and the validity of this opinion has never been appropriately tested. Using a
      proposed classification method in an IVF programme, it was estimated that a
      significant peritoneal bleeding occurred in 56/898 (6%) of IVF patients. Although
      Doppler ultrasound was routinely used in all patients, it did not predict 24/53
      (45%) of the patients with moderate peritoneal bleeding. In 8/53 cases (15%) with
      moderate peritoneal bleeding, vaginal bleeding was also detected and correctly
      predicted during oocyte aspiration using colour Doppler vaginal vessel imaging.
      Colour Doppler ultrasound guidance is an easily accessible technology with a
      theoretical promise to improve IVF safety and, with proper usage, has the
      potential to reduce haemorrhagic complications.

PMID- 20800547
TI  - Chromosome abnormality rates in human embryos obtained from in-vitro maturation
      and IVF treatment cycles.
AB  - The aim of this retrospective study was to compare the incidence of chromosomal
      abnormality in embryos from in-vitro maturation (IVM) and IVF cycles. The copy
      numbers of chromosomes 13, 15, 16, 18, 21, 22, X and Y were assessed with
      fluorescence in-situ hybridization (FISH) in single blastomeres biopsied from
      cleavage stage embryos. Spare embryos that were not transferred or cryopreserved
      were also analysed in full. IVM and IVF groups comprised six and 30 couples, with
      mean +/- SD embryos with FISH result of 8.0 +/- 4.4 and 11.7 +/- 3.8,
      respectively. The incidence of chromosomal abnormality per FISH result was
      similar in IVM and IVF embryos (58.7% versus 57.4%, respectively). When embryos
      were categorized based on maturation time of oocytes in IVM cycles, embryos
      derived from oocytes that matured 48 h after collection had a higher chromosomal
      abnormality rate compared with embryos derived from in-vivo matured oocytes and
      to embryos derived from oocytes that matured in the first 24 h after collection.

PMID- 20800548
TI  - The source and implications of progesterone rise during the follicular phase of
      assisted reproduction cycles.
AB  - Moderate elevations in serum progesterone concentrations are observed following
      the use of gonadotrophin-releasing hormone agonists during ovarian stimulation.
      The clinical significance of this phenomenon has been investigated, but findings
      have been inconclusive. This commentary proposes that progesterone concentrations
      are indeed important in endometrial advancement and oocyte/embryo development,
      which, may lead to asynchrony between endometrial and embryo development. Based
      on the two-cell, two-gonadotrophin model, this commentary proposes a hypothesis
      to describe how progesterone concentration increases during ovarian stimulation
      and three factors influencing this during ovarian stimulation are identified: the
      number of follicles, the FSH drive and the LH activity. It also suggests how
      differences in gonadotrophin preparations used for ovarian stimulation may have
      differential effects on progesterone synthesis. It remains to be tested whether
      routine measurement of late follicular progesterone concentrations may prove
      beneficial as suitable assay methods are now available. However, strategies that
      reduce follicular recruitment in high-responding women and gonadotrophins that
      contain LH activity may reduce the degree of progesterone elevation prior to
      luteinization.

PMID- 20800550
TI  - Pregnancy and live birth following the transfer of vitrified-warmed blastocysts
      derived from zona- and corona-cell-free oocytes.
AB  - This study reports two clinical pregnancies and one live birth following the
      transfer of vitrified blastocysts developed from oocytes with neither zona
      pellucida nor corona cells. Two zona-free oocytes obtained from two patients of
      advanced maternal age undergoing minimal stimulation were normally fertilized
      after intracytoplasmic sperm injection. In case 1, all four blastomeres of the
      zona-free embryo were loosely associated and inserted back into ruptured zona on
      day 2. Zona-free embryo from case 2 had tight contacts between blastomeres and
      was cultured without zona. Both embryos derived from zona-free oocytes progressed
      to blastocyst stage and were cryopreserved by vitrification. When patients came
      back for a cryopreserved embryo transfer, both vitrified blastocysts survived
      warming. In case 1, transfer of a warmed blastocyst with reconstructed zona
      resulted in a clinical pregnancy that ended in a spontaneous abortion at 22
      weeks. In case 2, live birth was achieved with a normal healthy baby (male)
      weighing 2381 g at 40 weeks' gestation. This report emphasizes the importance of
      maintenance of normal cell arrangement on the subsequent embryonic development
      for a zona-free oocyte. Zona-free oocytes may provide a valuable source of
      embryos for infertility patients, especially for those with a limited number of
      oocytes.

PMID- 20800549
TI  - Intracytoplasmic sperm injection outcome versus intracytoplasmic morphologically
      selected sperm injection outcome: a meta-analysis.
AB  - The development of a modified intracytoplasmic sperm injection (ICSI), called
      intracytoplasmic morphologically selected sperm injection (IMSI), demonstrated
      that a profound morphological investigation of the spermatozoon, under the
      magnification of 6600 x, enables outcome improvement. The aim of this study was
      to compare ICSI outcome with IMSI outcome. The meta-analysis results demonstrated
      no significant difference in fertilization rate between ICSI and IMSI groups.
      However, a significantly improved implantation (odds ratio (OR) 2.72; 95%
      confidence interval (CI) 1.50-4.95) and pregnancy rate (OR 3.12; 95% CI 1.55
      6.26) was observed in IMSI cycles. Moreover, the results showed a significantly
      decreased miscarriage rate (OR 0.42; 95% CI 0.23-0.78) in IMSI cycles as compared
      with ICSI cycles. This is the first meta-analysis of published data to evaluate
      the potential benefits of IMSI. The pooled data of IMSI cycles demonstrate a
      statistically significant improvement in implantation and pregnancy rates and a
      statistically significant reduction in miscarriage rates. However, more
      randomized controlled trials are needed to confirm these results.

PMID- 20800551
TI  - Cardiovascular and metabolic characteristics of infertile Chinese women with PCOS
      diagnosed according to the Rotterdam consensus criteria.
AB  - Polycystic ovary syndrome (PCOS) is strongly associated with metabolic
      abnormalities in Western women. However, data from other populations and
      geographical regions are scarce. This study evaluated cardiovascular and
      metabolic risk factors in Chinese infertile women diagnosed with PCOS using the
      2003 Rotterdam consensus criteria. A total of 615 women representing the four
      PCOS phenotypes (oligo- or anovulation (AO)+hyperandrogenism (HA)+polycystic
      ovaries (PCO), AO+HA, AO+PCO and HA+PCO) underwent standardized metabolic
      screening including a 75g oral glucose tolerance test. All groups presented with
      similar reproductive characteristics, with the only difference being a
      significantly higher Ferriman-Gallwey score for hirsutism (P=0.01) in the
      subgroup characterized by HA+PCO. Overall, the prevalence of metabolic syndrome
      was 6.4%, with no difference among the four groups (range of 2.3-12.2%).
      Metabolic syndrome was associated with body mass index (P<0.001), waist/hip ratio
      (P=0.002), index of insulin resistance (P=0.005) and fasting insulin (P=0.009) in
      multivariate analysis. Compared with Caucasians and Chinese women in Westernized
      societies, mainland Chinese women with PCOS have a low risk of metabolic syndrome
      and its presence does not vary across the specific PCOS phenotypes.

PMID- 20800552
TI  - Occurrence and lateralizing value of "rare" peri-ictal vegetative symptoms in
      temporal lobe epilepsy.
AB  - We retrospectively investigated rare peri-ictal vegetative symptoms (PIVS) in 380
      seizures of 97 patients with temporal lobe epilepsy (TLE): 234 seizures of 60
      patients with TLE with mesiotemporal sclerosis (TLE/MTS) and 146 seizures of 37
      patients with TLE with other lesions (TLE/non-MTS) who were at least 2 years
      after epilepsy surgery and classified as Engel I. We assessed the following PIVS:
      peri-ictal cough (pC), peri-ictal water drinking (pWD), peri-ictal vomiting (pV),
      and peri-ictal spitting (pS). We observed pC in 24.7% of patients and 10% of
      seizures; pWD in 14.4% of patients and 5.9% of seizures; pV and pS occurred more
      rarely. Both pWD and pC occurred significantly more often in those with TLE of
      the non- language-dominant hemisphere. The limited occurrence of pV and pS made
      it impossible to perform statistical analysis for these symptoms. In patients
      with TLE, pC and pWD were quite frequent; we observed pV and pS less frequently.
      Both pC and pWD have a significant lateralizing value in TLE.

PMID- 20800553
TI  - Peri-ictal yawning lateralizes the seizure onset zone to the nondominant
      hemisphere in patients with temporal lobe epilepsy.
AB  - The main aim of this retrospective study was to investigate the incidence and
      lateralizing value of peri-ictal yawning in patients with temporal lobe epilepsy
      (TLE) who underwent successful surgery for epilepsy (Engel class I outcome at the
      2-year follow-up visit). We reviewed a total of 97 patients (59 men and 38
      women). Fifty-three patients had TLE arising from the nondominant temporal lobe,
      and 44 had TLE arising from the dominant temporal lobe. In total, we reviewed 380
      seizures. Of those, 202 seizures arose from the nondominant temporal lobe and 178
      from the dominant one. Peri-ictal yawning was observed in 4 of 97 patients (4.1%)
      and in 7 of 380 seizures (1.8%), in the postictal period in all cases. Peri-ictal
      yawning occurred only in patients with right-sided, nondominant TLE. It may have
      a lateralizing value.

PMID- 20800554
TI  - Vagus nerve stimulation for drop attacks in a pediatric population.
AB  - A retrospective analysis of 43 patients with drop attack seizures who were
      treated with vagus nerve stimulation (VNS) was undertaken to determine the
      efficacy of VNS and to determine pre-implantation characteristics associated with
      VNS success. It was found that on last follow-up, 46% of patients had at least a
      75% reduction in drops per day. Forty-six percent of patients had less than a 50%
      reduction in drops per day and were considered nonresponders. Univariate analysis
      failed to uncover significant associations between pre-implantation
      characteristics and VNS success. It was found that atonic head nods were more
      amenable to VNS treatment as compared with atonic or tonic drop attacks. In
      addition, patients with focal or lateralized epileptiform abnormalities responded
      better to VNS compared with those with more diffuse or poorly localized findings
      on ictal and/or interictal recordings. Our data suggest that VNS offers
      significant palliative benefit to many children with medically intractable drop
      attack seizures.

PMID- 20800556
TI  - GC-FPD measurement of urinary dialkylphosphate metabolites of organophosphorous
      pesticides as pentafluorobenzyl derivatives in occupationally exposed workers and
      in a general population in Shanghai (China).
AB  - Measurement of organophosphorus (OP) pesticide metabolites in human biological
      fluids is an important biomarker of pesticides exposure. We measured the urinary
      excretion of OP pesticide metabolites to evaluate occupational and non
      occupational exposure to OP pesticides in the Chinese population in Shanghai
      (Eastern China). We collected urine samples from 30 exposed workers in a
      dimethoate emulsion packing division and from 60 healthy adults without any
      report of occupational exposure. DMP, DMTP, DMDTP, DEP, DEDP and DEDTP were
      measured by GC-FPD after derivatization with pentafluorobenzyl bromide. The LOQ
      values (1 mL urine) were 2.0 MUg/L for DMP and DETP, 4.0 MUg/L for DEP and DEDTP,
      8.0 MUg/L for DMDTP, and 10.0 MUg/L for DMTP. Dimethyl phosphates were detected
      in the majority of the urine samples, i.e., 90-100% in the exposed group and 80
      87% in the control group. The concentration of the urinary diethyl phosphates DEP
      and DETP was above the LOQ values in 40 and 20% of samples for the exposed group,
      and in 50 and 30% of the samples for the control group, respectively. DEDTP was
      not detectable in the urine samples except for a post-shift exposed worker
      (detection frequency, 6.7%). Median creatinine-adjusted values (MUg/gcr.) for DAP
      in Chinese with pre-shift, post-shift and without occupational exposure to OP
      were 316, 584 and 170 for DMP, below LOQ, 115 and 114 for DEP, 840, 1730 and 693
      for DMTP, and 255, 756 and 135 for DMDTP, respectively. In all subjects, the
      highest excretion levels were found for DMTP. Several OP pesticide metabolites
      were frequently detected in urine samples of both populations studied.

PMID- 20800555
TI  - Telomeric repeat mutagenicity in human somatic cells is modulated by repeat
      orientation and G-quadruplex stability.
AB  - Telomeres consisting of tandem guanine-rich repeats can form secondary DNA
      structures called G-quadruplexes that represent potential targets for DNA repair
      enzymes. While G-quadruplexes interfere with DNA synthesis in vitro, the impact
      of G-quadruplex formation on telomeric repeat replication in human cells is not
      clear. We investigated the mutagenicity of telomeric repeats as a function of G
      quadruplex folding opportunity and thermal stability using a shuttle vector
      mutagenesis assay. Since single-stranded DNA during lagging strand replication
      increases the opportunity for G-quadruplex folding, we tested vectors with G-rich
      sequences on the lagging versus the leading strand. Contrary to our prediction,
      vectors containing human [TTAGGG]10 repeats with a G-rich lagging strand were
      significantly less mutagenic than vectors with a G-rich leading strand, after
      replication in normal human cells. We show by UV melting experiments that G
      quadruplexes from ciliates [TTGGGG]4 and [TTTTGGGG]4 are thermally more stable
      compared to human [TTAGGG]4. Consistent with this, replication of vectors with
      ciliate [TTGGGG]10 repeats yielded a 3-fold higher mutant rate compared to the
      human [TTAGGG]10 vectors. Furthermore, we observed significantly more mutagenic
      events in the ciliate repeats compared to the human repeats. Our data demonstrate
      that increased G-quadruplex opportunity (repeat orientation) in human telomeric
      repeats decreased mutagenicity, while increased thermal stability of telomeric G
      quadruplexes was associated with increased mutagenicity.

PMID- 20800557
TI  - Simultaneous determination of a novel antifibrotic agent and three metabolites in
      human urine by LC-MS/MS.
AB  - A robust and validated high performance liquid chromatography tandem mass
      spectrometry (LC-MS/MS) method has been developed for simultaneous determination
      of F351 (5-methyl-1-(4-hydroxylphenyl)-2-(1H)-pyridone) and three major
      metabolites in human urine sample. This assay method has also been validated in
      terms of selectivity, linearity, lower limit of quantification (LLOQ), accuracy,
      precision, stability, matrix effect and recovery. Chromatography was carried out
      on an XTerra RP 18 column and mass spectrometric analysis was performed using an
      API 4000 mass spectrometer coupled with electro-spray ionization (ESI) source in
      the positive ion mode. The MRM transitions of m/z 202-->109, 232-->93, 282-->202
      and 378-->202 were used to quantify F351 and three metabolites, respectively.
      Retention times for F351 and three metabolites were 2.54, 1.38, 1.53 and 1.34
      min, respectively. The assay was validated from 20 to 4000 ng/mL for F351 and M1,
      from 80 to16,000 ng/mL for M2 and M3. Intra- and inter-day precision for all
      analytes was <6.3%, method accuracy was between -11.2 and 0.3%. This assay was
      used to support a clinical study where multiple oral doses were administered to
      healthy subjects to investigate the pharmacokinetics, safety, and tolerability of
      F351.

PMID- 20800558
TI  - The relationship between height and economic development in Spain, 1850-1958.
AB  - We investigate the relationship between height and some economic-development
      indicators in modern Spain by means of a recently constructed times series of
      data on conscripts. We estimate a Vector Autoregressive Equilibrium Correction
      Model (VECqM) to quantify the height and GDP per capita response to various
      living-standard indicators. We observe that conditions that perpetuate an
      elevated level of sickness and mortality and that raise the relative price of
      consumption goods tend to impede human growth, as reflected in a decline in
      average adult height, whereas factors that promote the purchase of health
      services and that help to open up the economy to international trade and ideas
      have tended to have an opposite effect from the 1850s onward. Our results also
      indicate that neither the level of per capita GDP nor its growth rate has a
      unidirectional relation to various measures of living standards, chiefly adult
      stature. Instead, our findings suggest that there may be behavioral factors
      (e.g., emphasis on health services), political factors (e.g., degree of
      openness), and economic factors (e.g., relative consumer costs to GDP deflator)
      whose affects may have been influenced the level of GDP, over the sample period.

PMID- 20800560
TI  - Prediction of response in rectal cancer: we are still far from the "crystal
      ball".

PMID- 20800561
TI  - Factor structure of the Sociocultural Attitudes Towards Appearance Questionnaire
      3 (SATAQ-3) among adolescent boys in China.
AB  - There is considerable evidence that mass media portrayals of body image
      contribute to body dissatisfaction, yet the assessment of perceived media
      influences has been examined fleetingly in highly populated, non-Western
      cultures, particularly among young males. This research examined the factor
      structure of the Sociocultural Attitudes Towards Appearance Questionnaire-3
      (SATAQ-3) among adolescent boys in China. In an initial exploratory factor
      analysis (N=719), a four factor solution emerged with components reflecting
      General Pressure-Internalization, Sources of Appearance Information, Pressure
      Internalization of an Athletic Ideal, and Pressure to be Thin. Subsequently,
      confirmatory factor analyses in a new sample (n=749) assessed fits of the derived
      four factor model, a three factor variant, and alternatives reflecting "Western"
      and "Malay" SATAQ-3 solutions. The derived four factor solution had the most
      acceptable structure across several fit indices. Patterns of correlation with
      other self-report measures also provided preliminary support for the validity of
      the derived solution.

PMID- 20800559
TI  - Genomic instability and copy-number heterogeneity of chromosome 19q, including
      the kallikrein locus, in ovarian carcinomas.
AB  - Many tissue kallikrein (KLK) genes and proteins are candidate diagnostic,
      prognostic and predictive biomarkers for ovarian cancer (OCa). We previously
      demonstrated that the KLK locus (19q13.3/4) is subject to copy-number gains and
      structural rearrangements in a pilot study of cell lines and ovarian cancer
      primary tissues, shown to overexpress KLK gene family members. To determine the
      overall frequency of genomic instability and copy-number changes, a retrospective
      study was conducted using formalin-fixed paraffin embedded (FFPE) tissues. Eighty
      one chemotherapy naive serous OCas were examined using 3-colour fluorescence in
      situ hybridization (FISH) to identify structural and numerical changes on 19q,
      including the KLK locus; in addition to immunohistochemistry (IHC) for KLK6,
      which has been shown to be overexpressed in OCa. The KLK locus was subject to
      copy-number changes in ~83% of cases: net gain in 51%, net loss in 30% and
      amplified in 2%; and found to be chromosomally unstable (p < 0.001). All cases
      showed a wide range of immuoreactivity for KLK6 by IHC. Although no strong
      correlation could be found with copy-number, the latter was contributing factor
      to the observed KLK6 protein overexpression. Moreover, univariate and
      multivariate analyses showed an association between the net loss of the KLK locus
      and longer disease-free survival. Interestingly, FISH analyses indicated that
      chromosome 19q was subjected to structural rearrangement in 62% of cases and was
      significantly correlated to tumor grade (p < 0.001). We conclude that numerical
      and structural aberrations of chromosome 19q, affect genes including the KLK gene
      members, may contribute to ovarian carcinoma progression and aggressiveness.

PMID- 20800563
TI  - Cochrane systematic reviews in orthodontics.
AB  - INTRODUCTION: The Cochrane Collaboration is an international scientific not-for
      profit organization the purpose of which is to produce and distribute systematic
      reviews of randomized clinical trials. The aim of this paper is to list the
      different existing Cochrane systematic reviews in the field of dentofacial
      orthopedics (DFO) and to analyse their main features. MATERIAL AND METHODS: The
      choice of Cochrane systematic reviews based on dentofacial orthopedics was made
      from the exhaustive list published by the Cochrane Oral Health Group. RESULTS: A
      total of 12 systematic Cochrane reviews related to dentofacial orthopedics were
      listed. All concluded on the need to conduct randomized clinical trials using
      more appropriate methodologies and comprising larger samples. None of these
      systematic reviews offered clear proof supporting any one form of treatment or
      treatment modality. DISCUSSION: Despite the lack of relevant conclusions in the
      still meagre number of Cochrane systematic reviews related to DFO, it is
      essential for orthodontists to regularly consult the reviews in the framework of
      their daily evidence-based orthodontic practice. This is true too for orthodontic
      researchers as clinical DFO research needs to be extended with the setting up of
      methodologically unquestionable randomized clinical trials. However, there exist
      alternatives to randomized clinical trials offering a lower level of proof but
      which are better suited to the field of dentofacial orthopedics.

PMID- 20800564
TI  - Impact of self-care programs for lower limb osteoarthritis and influence of
      patients' beliefs.
AB  - OBJECTIVE: To assess therapeutic education program impact for lower limb
      osteoarthritis (OA) at both the medical and surgical stage. Factors limiting
      efficiency and implementation of these programs such as patients' beliefs will be
      highlighted. METHOD: A non systematic literature review on Medline and Cochrane
      Library databases from 1966 to 2009 using following key words "knee/hip
      osteoarthritis", "self-care/therapeutic education", "total hip/knee
      replacement/arthroplasty", "patients' beliefs" is conducted. Clinical trials and
      randomized clinical trials, as well as literature reviews and practice
      guidelines, published in English and French will be analysed. RESULTS:
      Therapeutic education is part of the non-pharmacological management of chronic
      illnesses such as OA. The aim of education at an early stage of OA is to change
      patients' lifestyle, especially the regular practice of physical activity and
      weight reduction. Fears and avoidance assessment is necessary before patients'
      education process. When a surgical option is considered, the aim of education is
      to hasten patient recovery, improve autonomy after surgery, facilitate the return
      home and reduce the rate of transfer to a rehabilitation unit. CONCLUSION: The
      efficacy of therapeutic education could be optimised for the management of OA
      with use of standardized rules and methods to deliver information and education.
      One way to improve therapeutic education in the management of OA could be to
      propose dedicated continuing medical education programs supported by specific
      economic sources for health care professionals.

PMID- 20800565
TI  - Maternal body mass index and risk of testicular cancer in male offspring: a
      systematic review and meta-analysis.
AB  - OBJECTIVES: To date a number of studies have examined the association between
      maternal weight and testicular cancer risk although results have been largely
      inconsistent. This systematic review and meta-analysis investigated the nature of
      this association. METHODS: Search strategies were conducted in Ovid Medline (1950
      2009), Embase (1980-2009), Web of Science (1970-2009), and CINAHL (1937-2009)
      using keywords for maternal weight (BMI) and testicular cancer. RESULTS: The
      literature search produced 1689 hits from which 63 papers were extracted. Only 7
      studies met the pre-defined criteria. Random effects meta-analyses were
      conducted. The combined unadjusted OR (95% CI) of testicular cancer in the
      highest reported category of maternal BMI compared with the moderate maternal BMI
      was 0.82 (0.65-1.02). The Cochran's Q P value was 0.82 and the corresponding I(2)
      was 0%, both indicating very little variability among studies. The combined
      unadjusted OR (95% CI) for testicular cancer risk in the lowest reported category
      of maternal BMI compared to a moderate maternal BMI category was 0.88 (0.65
      1.20). The Cochran's Q P value was 0.05 and the corresponding I(2) was 54%,
      indicating evidence of statistical heterogeneity. The combined unadjusted OR (95%
      CI) of testicular cancer risk per unit increase in maternal BMI was 1.01 (0.97
      1.06). The Cochran's Q test had a P value of 0.05 and the corresponding I(2) was
      55% indicating evidence of statistical heterogeneity. CONCLUSION: This meta
      analysis, which included a small number of studies, showed that a higher maternal
      weight does not increase the risk of testicular cancer in male offspring. Though
      an inverse association between high maternal BMI and testicular cancer risk was
      detected, it was not statistically significant. Further primary studies with
      adjustment for appropriate confounders are required.

PMID- 20800566
TI  - Motivation of French medical students to pursue surgical careers: results of
      national survey of 1742 students.
AB  - OBJECTIVES: Analyze the aspirations and personal motivations behind the choice of
      surgical specialties in a large sample of students in their 6th year of medical
      school. MATERIAL AND METHODS: In December 2008, 2588 students participated in a
      nation-wide mock exam, before taking the National Ranking Exam. When they looked
      for their grades on the web, the students were prompted to answer a questionnaire
      containing socio-demographic questions concerning their choice and motivation to
      pursue a career in a surgical specialty. The survey called also for listing the
      three main factors (out of a list of 11) motivating their choice. RESULTS:
      Students originated from 39 medical schools. Of the 2588 students, 1427 (55%)
      were women. The response rate to the questionnaire was 1742/2588=67%. Two hundred
      and twenty students (13%) did not express any specific professional orientation.
      Of the 1522 responses obtained, 522 students wanted to become surgeons. Gender
      was a determining factor as 44% of male students (n=252) versus 29% of female
      students wanted to become a surgeon; P<0.0001. The three most selected surgical
      subspecialties were gynecology (n=137), orthopedics (n=91) and ophthalmology
      (n=57). Once again gender played a role in the choice: 82% who chose gynecology
      were women while 73% of future urologists were men (P<0.0001). Special interest
      in specific diseases (n=356, 23%), the possibility of private practice (n=280,
      18%) and life style (n=175, 11%) were the motivations most often cited to back
      their choice. CONCLUSION: One third of medical students want to become surgeons.
      Feminization, life style and income are the principal factors influencing the
      choice of the type of surgical subspecialization.

PMID- 20800567
TI  - Injury patterns in female Irish dancers.
AB  - OBJECTIVE: To determine the type of Irish dance injuries requiring evaluation and
      treatment by a sports medicine physician. DESIGN: Cross-sectional retrospective
      chart review. SETTING: Academic sports medicine center in the Midwest.
      PARTICIPANTS: Female Irish dancers who presented at an academic sports medicine
      center from June 2002 to September 2009. MAIN OUTCOME MEASURES: This was a
      retrospective chart review identifying injuries sustained to female Irish dancers
      in a single Irish dance company in a major metropolitan area. Dancers were
      evaluated and injuries were diagnosed by one sports medicine physician at an
      academic sports medicine center. RESULTS: Sixty-nine female Irish dancers, ages 8
      to 23 years, sustained 217 recorded injuries. The top injuries included stress
      fractures (29.9%), patellofemoral pain syndrome (11.1%), Sever condition (6.0%),
      ankle sprains (5.1%), posterior tibialis tendonitis (4.6%), and plantar fasciitis
      (4.6%). The most common site for stress fractures were the sesamoids, comprising
      27.7% of all stress fractures and 8.3% of total injuries. The majority of
      injuries were in the lower extremities (94.9%), remaining injuries involved the
      lumbosacral spine and pelvis (5.1%). Most dancers (79.7%) had multiple injuries.
      The number of injuries per dancer increased as the dancer's level increased.
      There was a trend for the average age of the dancers to decrease as the level of
      skill increased. CONCLUSION: Lower extremity injuries comprised the majority of
      Irish dance injuries. Stress fractures (29.9%), patellofemoral pain syndrome
      (11.1%), and Sever condition (6.0%) were the most common injuries.

PMID- 20800568
TI  - Accuracy of the Kato-Katz, adhesive tape and FLOTAC techniques for helminth
      diagnosis among children in Kyrgyzstan.
AB  - The purpose of this study was to assess the accuracy of three copro-microscopic
      techniques for helminth diagnosis: Kato-Katz, adhesive tape and FLOTAC. A total
      of 163 children from a peri-urban municipality near Bishkek, Kyrgyzstan,
      participated and submitted multiple stool samples and adhesive tapes. Ninety
      children supplied at least two stool samples and two adhesive tapes. Three stool
      samples and three adhesive tapes were available from 71 and 64 children,
      respectively. From each stool sample, a single Kato-Katz thick smear was prepared
      and examined quantitatively. Additionally, the first stool sample was subjected
      to the FLOTAC technique and helminth eggs were counted. Adhesive tapes were
      checked for the presence of Enterobius vermicularis eggs. Using pooled results as
      a diagnostic 'gold' standard, the prevalence of Ascaris lumbricoides, E.
      vermicularis, Hymenolepis nana and Dicrocoelium dendriticum were 54.4%, 13.3%,
      11.1% and 11.1%, respectively. Infection intensities were low. When compared to
      triplicate Kato-Katz, a single FLOTAC was more sensitive for the diagnosis of A.
      lumbricoides (89.5% versus 39.5%) and D. dendriticum (88.9% versus 33.3%), but
      less sensitive for H. nana (66.7% versus 88.9%). For E. vermicularis, three
      adhesive tapes showed much higher sensitivity than a single FLOTAC (92.9% versus
      14.3%). FLOTAC yielded significantly higher faecal egg counts than Kato-Katz for
      A. lumbricoides and D. dendriticum. Overall results suggest that, although FLOTAC
      represents a promising technique for helminth diagnosis in Kyrgyzstan, the
      repeated adhesive tape test remains so far the method of choice for diagnosing E.
      vermicularis.

PMID- 20800569
TI  - Ubiquinol (QH(2)) functions as a negative regulator of purine nucleotide
      inhibition of Acanthamoeba castellanii mitochondrial uncoupling protein.
AB  - We compared the influence of different adenine and guanine nucleotides on the
      free fatty acid-induced uncoupling protein (UCP) activity in non-phosphorylating
      Acanthamoeba castellanii mitochondria when the membranous ubiquinone (Q) redox
      state was varied. The purine nucleotides exhibit an inhibitory effect in the
      following descending order: GTP>ATP>GDP>ADP?GMP>AMP. The efficiency of guanine
      and adenine nucleotides to inhibit UCP-sustained uncoupling in A. castellanii
      mitochondria depends on the Q redox state. Inhibition by purine nucleotides can
      be increased with decreasing Q reduction level (thereby ubiquinol, QH2
      concentration) even with nucleoside monophosphates that are very weak inhibitors
      at the initial respiration. On the other hand, the inhibition can be alleviated
      with increasing Q reduction level (thereby QH2 concentration). The most important
      finding was that ubiquinol (QH2) but not oxidised Q functions as a negative
      regulator of UCP inhibition by purine nucleotides. For a given concentration of
      QH2, the linoleic acid-induced GTP-inhibited H(+) leak was the same for two types
      of A. castellanii mitochondria that differ in the endogenous Q content. When
      availability of the inhibitor (GTP) or the negative inhibition modulator (QH2)
      was changed, a competitive influence on the UCP activity was observed. QH2
      decreases the affinity of UCP for GTP and, vice versa, GTP decreases the affinity
      of UCP for QH2. These results describe the kinetic mechanism of regulation of UCP
      affinity for purine nucleotides by endogenous QH2 in the mitochondria of a
      unicellular eukaryote.

PMID- 20800570
TI  - Quantitative evaluation of the intrinsic uncoupling modulated by ADP and P(i) in
      the reconstituted ATP synthase of Escherichia coli.
AB  - The ATP synthase from Escherichia coli was isolated and reconstituted into
      liposomes. The ATP hydrolysis by these proteoliposomes was coupled to proton
      pumping, and the ensuing inner volume acidification was measured by the
      fluorescent probe 9-amino-6-chloro-2-methoxyacridine (ACMA). The ACMA response
      was calibrated by acid-base transitions, and converted into internal pH values.
      The rates of internal acidification and of ATP hydrolysis were measured in
      parallel, as a function of P(i) or ADP concentration. Increasing P(i)
      monotonically inhibited the hydrolysis rate with a half-maximal effect at 510MUM,
      whereas it stimulated the acidification rate up to 100-200MUM, inhibiting it only
      at higher concentrations. The ADP concentration in the assay, due both to
      contaminant ADP in ATP and to the hydrolysis reaction, was progressively
      decreased by means of increasing pyruvate kinase activities. Decreasing ADP
      stimulated the hydrolysis rate, whereas it inhibited the internal acidification
      rate. The quantitative analysis showed that the relative number of translocated
      protons per hydrolyzed ATP, i.e. the relative coupling ratio, depended on the
      concentrations of P(i) and ADP with apparent K(d) values of 220MUM and 27nM
      respectively. At the smallest ADP concentrations reached, and in the absence of
      P(i), the coupling ratio dropped down to 15% relative to the value observed at
      the highest ADP and P(i) concentrations tested. In addition, the data indicate
      the presence of two ADP and P(i) binding sites, of which only the highest
      affinity one is related to changes in the coupling ratio.

PMID- 20800571
TI  - Inserting membrane proteins: the YidC/Oxa1/Alb3 machinery in bacteria,
      mitochondria, and chloroplasts.
AB  - The evolutionarily conserved YidC/Oxa1p/Alb3 family of proteins plays important
      roles in the membrane biogenesis in bacteria, mitochondria, and chloroplasts. The
      members in this family function as novel membrane protein insertases, chaperones,
      and assembly factors for transmembrane proteins, including energy transduction
      complexes localized in the bacterial and mitochondrial inner membrane, and in the
      chloroplast thylakoid membrane. In this review, we will present recent progress
      with this class of proteins in membrane protein biogenesis and discuss the
      structure/function relationships. This article is part of a Special Issue
      entitled Protein translocation across or insertion into membranes.

PMID- 20800572
TI  - Negative regulation of neuronal cell differentiation by INHAT subunit SET/TAF
      Ibeta.
AB  - Epigenetic modification plays an important role in transcriptional regulation. As
      a subunit of the INHAT (inhibitor of histone acetyltransferases) complex, SET/TAF
      Ibeta evidences transcriptional repression activity. In this study, we
      demonstrate that SET/TAF-Ibeta is abundantly expressed in neuronal tissues of
      Drosophila embryos. It is expressed at high levels prior to and in early stages
      of neuronal development, and gradually reduced as differentiation proceeds.
      SET/TAF-Ibeta binds to the promoters of a subset of neuronal development markers
      and negatively regulates the transcription of these genes. The results of this
      study show that the knockdown of SET/TAF-Ibeta by si-RNA induces neuronal cell
      differentiation, thus implicating SET/TAF-Ibeta as a negative regulator of
      neuronal development.

PMID- 20800574
TI  - Regulation of the Polycomb protein RING1B ubiquitination by USP7.
AB  - The E3 ubiquitin ligase RING1B plays an important role in Polycomb-mediated gene
      silencing by monoubiquitinating histone H2A. Both the activity and stability of
      RING1B are controlled by ubiquitination in two distinct manners. Self
      ubiquitination of RING1B generates K6, K27 and K48-based mixed polyubiquitin
      chain, and is required for its activity as a ligase. On the other hand, its
      proteasomal degradation is mediated by another ligase; E6-AP catalyzes the
      formation of K48-based chains. Since these two modes of ubiquitination target the
      same lysine residues and are therefore mutually exclusive, an important mode of
      regulation of RING1B should be at the level of deubiquitination. Here we identify
      USP7 as a deubiquitinating enzyme that regulates the ubiquitination state of
      RING1B. RING1B interacts with USP7, which is mediated in part by its RING domain.
      In addition, USP7 was found in a complex with other Polycomb proteins, suggesting
      a broad role in regulating these complexes. Although, USP7 directly and
      specifically deubiquitinates RING1B in vitro and in vivo, it does not
      discriminate between the activating and proteolysis-targeting modes of
      ubiquitination, and therefore has a stabilizing effect on RING1B.

PMID- 20800575
TI  - Dimeric and tetrameric forms of enoyl-acyl carrier protein reductase from
      Bacillus cereus.
AB  - Enoyl-[acyl carrier protein] reductase (ENR) is an essential enzyme in type II
      fatty-acid synthesis that catalyzes the last step in each elongation cycle. Thus
      far FabI, FabL and FabK have been reported to carry out the reaction, with FabI
      being the most characterized. Some bacteria have more than one ENR, and Bacillus
      cereus has two (FabI and FabL) reported. Here, we have determined the crystal
      structures of the later in the apo form and in the ternary complex with NADP(+)
      and an indole naphthyridinone inhibitor. The two structures are almost identical,
      except for the three stretches that are disordered in the apo form. The apo form
      exists as a homo-dimer in both crystal and solution, while the ternary complex
      forms a homo-tetramer. The three stretches disordered in the apo structure are
      important in the cofactor and the inhibitor binding as well as in tetramer
      formation.

PMID- 20800573
TI  - BAG3 directly associates with guanine nucleotide exchange factor of Rap1,
      PDZGEF2, and regulates cell adhesion.
AB  - BAG3, a member of the Hsc70 binding co-chaperone BAG-family proteins, has
      critical roles in regulating actin organization, cell adhesion, cell motility and
      tumor metastasis. The PDZ domain containing guanine nucleotide exchange factor 2
      (PDZGEF2) was cloned as a BAG3-interacting protein. PDZGEF2 induces activation of
      Rap1 and increases integrin-mediated cell adhesion. The PPDY motif at the C
      terminus of PDZGEF2 binds to the WW domain of BAG3 in vitro and in vivo. BAG3
      deletion mutant lacking the WW domain lose its cell adhesion and motility
      activity. Gene knockdown of PDZGEF2 leads to the loss of cell adhesion on
      fibronectin-coated plates while BAG3 overexpression increases cell adhesion in
      Cos7 cells, but not in PDZGEF2 gene knockdown cells indicating that PDZGEF2 is a
      critical partner for BAG3 in regulating cell adhesion.

PMID- 20800576
TI  - Amino acid residues involved in organic solvent-stability of the LST-03 lipase.
AB  - LST-03 lipase from Pseudomonas aeruginosa LST-03 is highly active and stable in
      the presence of various organic solvents. To further characterize and improve the
      organic solvent-stability of the LST-03 lipase, residues that potentially provide
      this stability were identified and mutated to other amino acids in an effort to
      increase the organic solvent-stability of the protein. S155L, G157R, S164K,
      S194R, and D209N mutations were found to improve the organic solvent-stability of
      the wild-type LST-03 lipase. Such mutations were found to induce structural
      changes, including the formation of a salt bridge, hydrogen bonds, lead to an
      improved packing of the hydrophobic core, and pI shift of side chain. These
      changes increased the stability of the protein, thereby improving the organic
      solvent-stability of the wild-type LST-03 lipase. In addition, a single mutation
      was found to stabilize the lipase by single or multiple factors.

PMID- 20800577
TI  - Non-acylated Mycobacterium bovis glycoprotein MPB83 binds to TLR1/2 and
      stimulates production of matrix metalloproteinase 9.
AB  - A variety of Mycobacterium tuberculosis cell wall components induce expression of
      matrix metalloproteinase 9 (MMP-9) by monocytic cells and levels of MMP-9 in vivo
      positively correlate with severity of disease. Toll-like receptor (TLR)2 mediates
      cellular responses to acylated molecules but can also mediate responsiveness to
      diverse molecular structures, including non-acylated native viral and bacterial
      proteins. MPT/B-83 is a cell-associated lipoglycoprotein common to M.
      tuberculosis and M. bovis and an important antigen during infection of cattle.
      Since MPB83 is acylated and glycosylated, we investigated whether MPB83 would
      induce MMP-9 expression via interaction with TLR2, and assessed the contribution
      of the lipid, glycan and polypeptide components to its activity. Acylated peptide
      derived from MPB83 stimulated MMP-9 expression by human macrophage cells via
      interaction with both TLR2 and TLR1, but not TLR4. Lesser induction was found
      with secreted (non-acylated, but glycosylated) MPB83 protein purified from
      culture of M. bovis. Stimulation of cells with MPB83 induced TNF-alpha production
      which acted to upregulate MMP-9 expression. Surprisingly, recombinant MPB83
      protein devoid of any post-translational modification also induced MMP-9
      expression. Direct interaction of RecMPB83 with TLR2 was demonstrated by surface
      plasmon-resonance. MPB83 may act as a virulence factor through TLR2 mediated
      induction of MMP-9.

PMID- 20800578
TI  - Bcl3-dependent stabilization of CtBP1 is crucial for the inhibition of apoptosis
      and tumor progression in breast cancer.
AB  - B-cell lymphoma 3 (Bcl3) is a proto-oncogene upregulated in a wide range of
      cancers, including breast cancer. Although Bcl3 is known to promote cell
      proliferation and inhibit apoptosis, the molecular mechanisms underlying the
      proto-oncogenic function of Bcl3 have not been completely elucidated. To gain
      insight into the oncogenic role of Bcl3, we applied a proteomic approach, which
      led to the identification of C-terminal binding protein 1 (CtBP1) as a binding
      partner of Bcl3. A PXDLS/R motif embedded in Bcl3 was found to mediate the
      interaction between Bcl3 and CtBP1, which caused the stabilization of CtBP1 by
      blocking proteasome-dependent degradation. Apoptotic stimuli-induced degradation
      of CtBP1 was significantly abolished by the upregulation of Bcl3, leading to the
      sustained repression of pro-apoptotic gene expression and subsequent inhibition
      of apoptosis. Intriguingly, a strong positive correlation between the protein
      levels of Bcl3 and CtBP1 was detected in breast cancer patient samples. Our study
      reveals a novel combinatorial role for Bcl3 and CtBP1, providing an explanation
      for the acquisition of resistance to apoptosis in cancer cells, which is a major
      requirement for cancer development.

PMID- 20800579
TI  - The role of the glycine triad in human glutathione synthetase.
AB  - Experimental kinetics and computational modeling of human glutathione synthetase
      (hGS) support the significant role of the G-loop glycine triad (G369, G370, G371)
      for activity of this ATP-grasp enzyme. Enzyme kinetic experiments indicate that
      G369V and G370V mutant hGS have little activity (<0.7 and 0.3%, respectively,
      versus wild-type hGS). However, G371V retains ~13% of the activity of wild-type
      hGS. With respect to G-loop:A-loop interaction in hGS, mutations at Gly369 and
      Gly370 decrease ligand binding and prevent active site closure and protection.
      This research indicates that Gly369 and Gly370 have essential roles in hGS, while
      Gly371 has a lesser involvement. Implications for glycine-rich ensembles in other
      phosphate-binding enzymes are discussed.

PMID- 20800580
TI  - Cleavage of peptide bonds bearing ionizable amino acids at P(1) by serine
      proteases with hydrophobic S(1) pocket.
AB  - Enzymatic hydrolysis of the synthetic substrate succinyl-Ala-Ala-Pro-Xxx-pNA
      (where Xxx=Leu, Asp or Lys) catalyzed by bovine chymotrypsin (CHYM) or
      Streptomyces griseus protease B (SGPB) has been studied at different pH values in
      the pH range 3-11. The pH optima for substrates having Leu, Asp, and Lys have
      been found to be 7.5-8.0, 5.5-6.0, and ~10, respectively. At the normally
      reported pH optimum (pH 7-8) of CHYM and SGPB, the substrate with Leu at the
      reactive site is more than 25,000-fold more reactive than that with Asp. However,
      when fully protonated, Asp is nearly as good a substrate as Leu. The pK values of
      the side chains of Asp and Lys in the hydrophobic S(1) pocket of CHYM and SGPB
      have been calculated from pH-dependent hydrolysis data and have been found to be
      about 9 for Asp and 7.4 and 9.7 for Lys for CHYM and SGPB, respectively. The
      results presented in this communication suggest a possible application of CHYM
      like enzymes in cleaving peptide bonds contributed by acidic amino acids between
      pH 5 and 6.

PMID- 20800581
TI  - The adipokine leptin increases skeletal muscle mass and significantly alters
      skeletal muscle miRNA expression profile in aged mice.
AB  - Age-associated loss of muscle mass, or sarcopenia, contributes directly to
      frailty and an increased risk of falls and fractures among the elderly. Aged mice
      and elderly adults both show decreased muscle mass as well as relatively low
      levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle
      mass and myofiber size with aging in mice is associated with significant changes
      in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs
      in mouse skeletal muscle, and many of these miRNAs are now reported to be
      associated specifically with age-related muscle atrophy. These include miR-221,
      previously identified in studies of myogenesis and muscle development as playing
      a role in the proliferation and terminal differentiation of myogenic precursors.
      We also treated aged mice with recombinant leptin, to determine whether leptin
      therapy could improve muscle mass and alter the miRNA expression profile of aging
      skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass
      and extensor digitorum longus fiber size in aged mice. Furthermore, the
      expression of 37 miRNAs was altered in muscles of leptin-treated mice. In
      particular, leptin treatment increased the expression of miR-31 and miR-223,
      miRNAs known to be elevated during muscle regeneration and repair. These findings
      suggest that aging in skeletal muscle is associated with marked changes in the
      expression of specific miRNAs, and that nutrient-related hormones such as leptin
      may be able to reverse muscle atrophy and alter the expression of atrophy-related
      miRNAs in aging skeletal muscle.

PMID- 20800584
TI  - Parkin dosage mutations in patients with early-onset sporadic and familial
      Parkinson's disease in Chinese: an independent pathogenic role.
AB  - Mutations in the parkin gene have been identified as one of the important genetic
      factors for the etiology of PD. However, pathogenicities of parkin mutations,
      especially of those heterozygotes, remain controversial, possibly due to
      confusions caused by the "mixed" effects of all types of mutations. Here we
      report a study on the independent effects of exonic deletions/duplications (or
      dosage mutations) on the risk for and clinical profiles of PD in a Chinese cohort
      consisting of 29 autosomal-recessive early-onset parkinsonism (AREP) families and
      173 patients with sporadic early-onset Parkinson's disease (EOPD). Detected
      simultaneously by multiplex PCR/denaturing high-performance liquid chromatography
      and real-time quantitative PCR analysis, heterozygous or homozygous dosage
      mutations were identified in exons 2-7 of parkin. The overall frequency of these
      mutations for both types of EOPD patients (8.91%, 18/202) was significantly
      higher than that of the controls (0%, 0/54) (p=0.03), and heterozygous mutations
      were more frequent in the AREP probands (17.2%, 5/29) than in the controls (0%)
      (p=0.004) and the sporadic EOPD cases (3.5%, 6/173) (p=0.01). AREP patients with
      dosage mutations had significantly younger age at onset (AAO) (p=0.000) and were
      more likely to present as bradykinesia and complicated with dystonia or
      dyskinesia compared with those without mutations. Sporadic EOPD patients with
      dosage mutations do not have an earlier AAO but are more likely to present as
      tremor and bradykinesia. These data suggested that dosage mutations alone can
      increase the risk for both sporadic and familial EOPD and affect their clinical
      aspects, but might contribute to a greater degree to familial EOPD.

PMID- 20800583
TI  - DL-3-n-butylphthalide prevents neuronal cell death after focal cerebral ischemia
      in mice via the JNK pathway.
AB  - DL-3-n-Butylphthalide (NBP) has shown cytoprotective effects in animal models of
      stroke and has passed clinical trials as a therapeutic drug for stroke in China.
      Hence, as a potential clinical treatment for stroke, understanding the
      mechanism(s) of action of NBP is essential. This investigation aimed to delineate
      the cellular and molecular mechanism of NBP protection in neuronal cultures and
      in the ischemic brain. NBP (10 MUM) attenuated serum deprivation-induced neuronal
      apoptosis and the production of reactive oxygen species (ROS) in cortical
      neuronal cultures. Adult male 129S2/sv mice were subjected to permanent occlusion
      of the middle cerebral artery (MCA). NBP (100 mg/kg, i.p.) administrated 2 hrs
      before or 1 hr after ischemia reduced ischemia-induced infarct formation,
      attenuated caspase-3 and caspase-9 activation in the ischemic brain. TUNEL
      positive cells and mitochondrial release of cytochrome c and apoptosis-inducing
      factor (AIF) in the penumbra region were reduced by NBP. The proapoptotic
      signaling mediated by phospho-JNK and p38 expression was downregulated by NBP
      treatment in vitro and in vivo. It is suggested that NBP protects against
      ischemic damage via multiple mechanisms including mitochondria associated caspase
      dependent and -independent apoptotic pathways. Previous and current studies and
      recent clinical trials encourage exploration of NBP as a neuroprotective drug for
      the treatment of ischemic stroke.

PMID- 20800582
TI  - Neurokinin B and the hypothalamic regulation of reproduction.
AB  - Loss-of-function mutations in the genes encoding either neurokinin B (NKB) or its
      receptor, NK3 (NK3R), result in hypogonadotropic hypogonadism, characterized by
      an absence of pubertal development and low circulating levels of LH and gonadal
      steroids. These studies implicate NKB and NK3R as essential elements of the human
      reproductive axis. Studies over the last two decades provide evidence that a
      group of neurons in the hypothalamic infundibular/arcuate nucleus form an
      important component of this regulatory circuit. These neurons are steroid
      responsive and coexpress NKB, kisspeptin, dynorphin, NK3R, and estrogen receptor
      alpha (ERalpha) in a variety of mammalian species. Compelling evidence in the
      human indicates these neurons function in the hypothalamic circuitry regulating
      estrogen negative feedback on gonadotropin-releasing hormone (GnRH) secretion.
      Moreover, in the rat, they form a bilateral, interconnected network that projects
      to NK3R-expressing GnRH terminals in the median eminence. This network provides
      an anatomical framework to explain how coordination among
      NKB/kisspeptin/dynorphin/NK3R/ERalpha neurons could mediate feedback information
      from the gonads to modulate pulsatile GnRH secretion. There is substantial (but
      indirect) evidence that this network may be part of the neural circuitry known as
      the "GnRH pulse generator," with NK3R signaling as an important component. This
      theory provides a compelling explanation for the occurrence of hypogonadotropic
      hypogonadism in patients with inactivating mutations in the TAC3 or TACR3 genes.
      Future studies will be needed to determine whether NKB signaling plays a
      permissive role in the onset of puberty or is part of the driving force
      initiating the maturation of reproductive function.

PMID- 20800585
TI  - Synapse-to-neuron ratio is inversely related to neuronal density in mature
      neuronal cultures.
AB  - Synapse formation is a fundamental process in neurons that occurs throughout
      development, maturity, and aging. Although these stages contain disparate and
      fluctuating numbers of mature neurons, tactics employed by neuronal networks to
      modulate synapse number as a function of neuronal density are not well
      understood. The goal of this study was to utilize an in vitro model to assess the
      influence of cell density and neuronal maturity on synapse number and
      distribution. Specifically, cerebral cortical neurons were plated in planar
      culture at densities ranging from 10 to 5000 neurons/mm2, and synapse number and
      distribution were evaluated via immunocytochemistry over 21 days in vitro (DIV).
      High-resolution confocal microscopy revealed an elaborate three-dimensional
      distribution of neurites and synapses across the heights of high-density neuronal
      networks by 21 DIV, which were up to 18 MUm thick, demonstrating the complex
      degree of spatial interactions even in planar high-density cultures. At 7 DIV,
      the mean number of synapses per neuron was less than 5, and this did not vary as
      a function of neuronal density. However, by 21 DIV, the number of synapses per
      neuron had jumped 30- to 80-fold, and the synapse-to-neuron ratio was greatest at
      lower neuronal densities (< 500 neurons/mm2; mean approximately 400
      synapses/neuron) compared to mid and higher neuronal densities (500-4500
      neurons/mm2; mean of approximately 150 synapses/neuron) (p<0.05). These results
      suggest a relationship between neuronal density and synapse number that may have
      implications in the neurobiology of developing neuronal networks as well as
      processes of cell death and regeneration.

PMID- 20800586
TI  - Effects of anticoagulants on human plasma soluble corin levels measured by ELISA.
AB  - BACKGROUND: Recently, soluble corin was detected in human plasma. In patients
      with heart failure, plasma corin levels were lower than that of normal controls.
      In this study, we analyzed experimental conditions for measuring plasma or serum
      corin by an immunoassay. METHODS: Serum and plasma corin levels were measured by
      ELISA. Effects of different anticoagulants (EDTA, heparin and sodium citrate) on
      plasma corin levels were examined. RESULTS: Corin levels in serum were similar to
      that in plasma with heparin (950+/-305 vs. 929+/-301 pg/ml, n=40, p=0.73), but
      were significantly higher than those in plasma with sodium citrate (735+/-237
      pg/ml, p<0.01) or EDTA (716+/-261 pg/ml, p<0.001). Native and recombinant human
      corin proteins were stable in human plasma with EDTA at 4 degrees C or underwent
      freezing-and-thawing. In 348 healthy Chinese individuals, plasma corin levels
      ranged from 216 to 1663 pg/ml. The levels were higher in males than that in
      females (842+/-283 vs. 569+/-192 pg/ml, p<0.001). CONCLUSION: Soluble corin was
      stable in plasma samples. Plasma soluble corin levels vary depending on
      anticoagulants used. Samples containing heparin had significantly higher levels
      of corin than that in samples with EDTA or sodium citrate.

PMID- 20800587
TI  - Molecular pathology of haemophilia A in Indian patients: identification of 11
      novel mutations.
AB  - BACKGROUND: The identification of pathogenic mutations in haemophilia A (HA)
      patients is important as a basis for genetic diagnosis and also for the
      assessment of clinical manifestations. METHOD: We analyzed 36 inversion negative
      congenital HA cases (28 unrelated and 8 familial) by multiplex PCR and the
      conformation sensitive gel electrophoresis (CSGE) technique, followed by DNA
      sequencing. The pathogenicity of each of these mutations was assessed using
      various prediction software. RESULTS: We found 17 missense, 5 deletions, 3
      insertions, and 2 nonsense mutations, out of which 16 were recurrent and 11
      novel. All novel substitution mutations were found to be deleterious using the
      prediction softwares. We also encountered a double mutation (1 novel and 1 hot
      spot mutation) in a family with a strong family history. A missense mutation in
      heterozygous state was also detected in a female bleeder with very low factor
      VIII levels, probably due to extreme lyonization. CONCLUSION: High heterogeneity
      in mutational profile has been observed in the present study. The outcome of this
      study would enable us to give an accurate diagnosis in all affected families by
      direct mutation analysis.

PMID- 20800588
TI  - Development of a high resolution melting method for the detection of genetic
      variations in hypertrophic cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac
      disease affecting 1 in 500 people. Due to large cohorts to investigate, the
      number of disease-causing genes, the size of the 2 prevalent mutated genes, and
      the presence of a large spectrum of private mutations, mutational screening must
      be performed using an extremely sensitive and specific scanning method. METHODS:
      High Resolution Melting (HRM) analysis was developed for prevalent HCM-causing
      genes (MYBPC3, MYH7, TNNT2, and TNNI3) using control DNAs and DNAs carrying
      previously identified gene variants. A cohort of 34 HCM patients was further
      blindly screened. To evaluate HRM sensitivity, this cohort was also screened
      using an optimized DHPLC methodology. RESULTS: All gene variants detected by
      DHPLC were also readily identified as abnormal by HRM analysis. Mutational
      screening of a cohort of 34 HCM cases led to identification of 19 mutated
      alleles. Complete molecular investigation was completed two times faster and
      cheaper than using DHPLC strategy. CONCLUSIONS: HRM analysis represents an
      inexpensive, highly sensitive and high-throughput method to allow identification
      of mutations in the coding sequences of prevalent HCM genes. Identification of
      more HCM mutations will provide new insights into genotype/phenotype
      relationships and will allow a better knowledge of the HCM physiopathology.

PMID- 20800589
TI  - A rapid and sensitive protocol for prenatal molecular diagnosis of X-linked
      adrenoleukodystrophy.
AB  - BACKGROUND: X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative genetic
      disease characterized by progressive demylination of the brain, adrenal
      insufficiency and elevated VLCFA level. ABCD1gene is the disease gene and more
      than 500 unique mutations in the ABCD1gene have been recorded in the database,
      approximately 60% of which are noncurrent ones. Although great progress has been
      made in the treatment of X-ALD, prenatal diagnosis is still badly needed by X-ALD
      stricken families. METHODS: Twelve high-risk fetuses entered this study. Amniotic
      fluid (AF) was divided into two parts, with one part being used directly to
      isolate genomic DNA and debris from the other part for amniotic fluid cells (AFC)
      culturing. STR profiling was performed to evaluate maternal contamination of AFC
      genomic DNA. Two different molecular approaches, be they any two of direct
      sequencing, PCR-RFLP, ARMS, dot hybridization and DHPLC, were applied to
      determine whether the mutation identified in the index patient was found in the
      fetus. RESULTS: The genotypes of all 12 fetuses were determined, among which 2
      were diagnosed as ALD males, 5 unaffected males, 1 heterozygote, and 4 normal
      unaffected females. A total of 9 families sent samples of umbilical blood at the
      time of delivery, and results of molecular checking of these samples agreed with
      those of prenatal diagnosis. Up until now, no ALD-related abnormalities were
      reported postnatally. CONCLUSION: An in-house protocol for the prenatal molecular
      diagnosis of X-ALD was established, and this protocol would provide accurate and
      rapid prenatal genetic service to X-ALD-stricken families.

PMID- 20800590
TI  - Influences of sleep and the circadian rhythm on iron-status indices.
AB  - OBJECTIVES: The aim was to study the influence of sampling time, food intake and
      sleep on tests used to screen for and monitor conditions of iron deficiency and
      overload. DESIGN AND METHODS: The 24 h variations of iron, transferrin,
      transferrin saturation (TS) and ferritin were studied in seven healthy
      individuals during standardised food intake, and during night or day sleep.
      RESULTS: Iron and TS showed clear diurnal variations, with peaks at 12.6 h and
      12.8 h respectively, during night sleep, and at 19.7 h and 19.3 h, respectively,
      during day sleep. Ferritin did not demonstrate any circadian variation.
      Transferrin and ferritin were unaffected by sleep-condition. Meals did not have
      any effect except a slight decline of transferrin. CONCLUSIONS: Time of day and
      sleeping patterns had great influence on iron and TS, whereas no or only minor
      effects are seen on the concentration of ferritin and transferrin. Meals have
      limited effects.

PMID- 20800591
TI  - Applications of liquid chromatography coupled to mass spectrometry-based
      metabolomics in clinical chemistry and toxicology: A review.
AB  - The metabolome is the set of small molecular mass organic compounds found in a
      given biological media. It includes all organic substances naturally occurring
      from the metabolism of the studied living organism, except biological polymers,
      but also xenobiotics and their biotransformation products. The metabolic
      fingerprints of biofluids obtained by mass spectrometry (MS) or nuclear magnetic
      resonance (NMR)-based methods contain a few hundreds to thousands of signals
      related to both genetic and environmental contributions. Metabolomics, which
      refers to the untargeted quantitative or semi-quantitative analysis of the
      metabolome, is a promising tool for biomarker discovery. Although proof-of
      concept studies by metabolomics-based approaches in the field of toxicology and
      clinical chemistry have initially been performed using NMR, the use of liquid
      chromatography hyphenated to mass spectrometry (LC/MS) has increased over the
      recent years, providing complementary results to those obtained with other
      approaches. This paper reviews and comments the input of LC/MS in this field. We
      describe here the overall process of analysis, review some seminal papers in the
      field and discuss the perspectives of metabolomics for the biomonitoring of
      exposure and diagnosis of diseases.

PMID- 20800592
TI  - Exercise training enhances elastin, fibrillin and nitric oxide in the aorta wall
      of spontaneously hypertensive rats.
AB  - This work aimed to analyze the effect of low-intensity exercise training on
      ultrastructural and molecular aortic remodeling. Male Wistar-Kyoto rats (WKY) and
      spontaneously hypertensive rats (SHR) were allocated into four groups: sedentary
      WKY (SED-WKY), exercised WKY (EX-WKY, 1 h/day, 5 days/week treadmill exercise
      training), sedentary SHR (SED-SHR), and exercised SHR (EX-SHR). EX-SHR showed
      blood pressure reduction of 26% in comparison to SED-SHR after 1 month of
      exercise (P<0.05). At the 20th week, BP level was not different between EX-SHRs
      and WKYs. Circumferential wall tension (CWT) was higher by 77% in SED-SHRs than
      in SED-WKYs (P<0.001). Exercise training reduced CWT by 30% in EX- vs. SED-SHR
      (P<0.001). In SED-SHRs, endothelial cells showed large and numerous cytoplasmatic
      vacuoles, fragmented inner elastic lamina and scarce elastin and fibrillin, while
      exercise training ameliorated it in EX-SHR group. The highest eNOS immunodensity
      was observed in EX-SHR, which was 50% higher than EX-WKY (P<0.01) and 120% higher
      than SED-SHR (P<0.0001). In conclusion, present findings indicate beneficial
      effects of exercise training in hypertensive rats since it increased elastin,
      fibrillin and eNOS content in the aortic wall.

PMID- 20800593
TI  - Neuroprotection in glaucoma - Is there a future role?
AB  - In glaucoma, the major cause of global irreversible blindness, there is an urgent
      need for treatment modalities that directly target the RGCs. The discovery of an
      alternative therapeutic approach, independent of IOP reduction, is highly sought
      after, due to the indirect nature and limited effectiveness of IOP lowering
      therapy in preventing RGC loss. Several mechanisms have been implicated in
      initiating the apoptotic cascade in glaucomatous retinopathy and numerous drugs
      have been shown to be neuroprotective in animal models of glaucoma. These
      mechanisms and their potential treatment include excitotoxicity, protein
      misfolding, mitochondrial dysfunction, oxidative stress, inflammation and
      neurotrophin deprivation. All of these mechanisms ultimately lead to programmed
      cell death with loss of RGCs. In this article we summarize the mechanisms
      involved in glaucomatous disease, highlight the rationale for neuroprotection in
      glaucoma management and review current potential neuroprotective strategies
      targeting RGCs from the laboratory to the clinic.

PMID- 20800594
TI  - Knockdown of apoptosis signal-regulating kinase 1 modulates basal glycogen
      synthase kinase-3beta kinase activity and regulates cell migration.
AB  - GSK-3beta is a basally active kinase. Axin forms a complex with GSK-3beta and
      beta-catenin; this complex promotes the GSK-3beta-dependent phosphorylation of
      beta-catenin, thereby inducing its degradation. However, the inhibition of GSK
      3beta provokes cell migration via the dysregulation of beta-catenin. In this
      study, we determined that the level of apoptosis signal-regulating kinase 1
      (ASK1) was lower in a metastatic breast cancer cell line, compared to that of non
      metastatic cancer cell lines and the knockdown of ASK1 not only induces beta
      catenin activation via the inhibition of GSK-3beta and collapsing the subsequent
      protein complex by regulating Axin dynamics, but also stimulates cell migration.
      Together, the blockage of the GSK-3beta-beta-catenin pathway resulting from the
      knockdown of ASK1 modulates the migration of breast cancer cells.

PMID- 20800595
TI  - Perspectives on concordant and discordant relations between insulin-like growth
      factor 1 (IGF1) and growth in fishes.
AB  - Many physiological processes are modulated by the endocrine system, including
      growth. Insulin-like growth factor 1 is one of the primary hormones involved in
      growth regulation in vertebrates, including fishes. Current work on IGF1 in
      fishes is driven both by a desire to better understand mechanisms of growth as
      well as to develop a reliable index of growth rate. A review of studies relating
      IGF1 to growth broadly reveals positive and significant relations between IGF1
      and growth; however, relations found in individual studies range from no
      correlation to highly significant correlations. Potential sources for this
      variation include both biological and methodological issues and range from
      differences in how growth is defined (changes in length or weight), the duration
      of growth assessed (weeks to months) and how growth is calculated (total change,
      rate, percent change); yet, these methodological concerns cannot account for all
      the variation found. A further review of the literature reveals a number of
      physiological conditions and environmental factors that might influence IGF1
      level and the subsequent relation of that IGF1 level to growth rate. The term
      concordance is introduced to categorize factors that influence IGF1 and growth in
      a similar fashion, such that positive and significant relations between IGF1 and
      growth are maintained even though the factor stimulates changes in IGF1 level.
      Conversely, the term discordance is introduced to categorize factors that
      stimulate changes in the relations between IGF1 and growth, such that IGF1 is not
      an efficacious index of growth for both pre and post-stimulus fish combined. IGF1
      and growth relations generally remain concordant after changes in nutrition
      (consumption rate or diet). Differences in IGF1 level of juvenile, maturing male
      and maturing female fish are common and IGF1-growth relations appear discordant
      between these groups. Acute changes in temperature and salinity induce discordant
      relations between IGF1 and growth but acclimation to persistent differences in
      environmental condition generally result in concordant relations. Overall, by
      discriminating between fish of differing physiological status and discerning and
      categorizing differences among environments one may effectively use IGF1 as a
      growth index for fishes.

PMID- 20800596
TI  - Using T. brucei as a biological epitope-display platform to elicit specific
      antibody responses.
AB  - The African trypanosome (Trypanosoma brucei) is transmitted by the bite of the
      tsetse vector to the mammalian bloodstream where it exists as a completely
      extracellular parasite. As a result of this exposure, the parasite elicits a
      robust immune response that is almost exclusively antibody mediated, and is
      extremely specific to the trypanosome coat displayed on the surface. This coat is
      comprised of ~11 million copies of a single gpi-linked molecule (the variable
      surface glycoprotein or VSG) and can therefore be used as a powerful platform for
      the immunogenic display of antigenic determinants. Here we describe a method to
      display repetitive, ordered arrays of linear epitopes on the surface of T. brucei
      and to then use the engineered organisms to generate specific anti-epitope
      antibody responses, upon injection into mice. This method offers an alternative
      approach to generating anti-peptide antibodies, and could be a useful option in
      cases where more traditional methods have failed.

PMID- 20800597
TI  - Crystallographic snapshot of glycosylasparaginase precursor poised for
      autoprocessing.
AB  - Glycosylasparaginase belongs to a family of N-terminal nucleophile hydrolases
      that autoproteolytically generate their mature enzymes from single-chain protein
      precursors. Previously, based on a precursor structure paused at pre
      autoproteolysis stage by a reversible inhibitor (glycine), we proposed a
      mechanism of intramolecular autoproteolysis. A key structural feature, a highly
      strained conformation at the scissile peptide bond, had been identified and was
      hypothesized to be critical for driving autoproteolysis through an N-O acyl
      shift. To examine this "twist-and-break" hypothesis, we report here a 1. 9-A
      resolution structure of an autoproteolysis-active precursor (a T152C mutant) that
      is free of inhibitor or ligand and is poised to undergo autoproteolysis. The
      current crystallographic study has provided direct evidence for the natural
      conformation of the glycosylasparaginase autocatalytic site without influence
      from any inhibitor or ligand. This finding has confirmed our previous proposal
      that conformational strain is an intrinsic feature of an active precursor.

PMID- 20800598
TI  - Crystal structures of nucleosome core particles containing the '601' strong
      positioning sequence.
AB  - Nucleosome positioning plays a key role in genomic regulation by defining histone
      DNA context and by modulating access to specific sites. Moreover, the histone-DNA
      register influences the double-helix structure, which in turn can affect the
      association of small molecules and protein factors. Analysis of genomic and
      synthetic DNA has revealed sequence motifs that direct nucleosome positioning in
      vitro; thus, establishing the basis for the DNA sequence dependence of
      positioning would shed light on the mechanics of the double helix and its
      contribution to chromatin structure in vivo. However, acquisition of well
      diffracting nucleosome core particle (NCP) crystals is extremely dependent on the
      DNA fragment used for assembly, and all previous NCP crystal structures have been
      based on human alpha-satellite sequences. Here, we describe the crystal
      structures of Xenopus NCPs containing one of the strongest known histone octamer
      binding and positioning sequences, the so-called '601' DNA. Two distinct 145-bp
      601 crystal forms display the same histone-DNA register, which coincides with the
      occurrence of DNA stretching-overtwisting in both halves of the particle around
      five double-helical turns from the nucleosome center, giving the DNA an
      'effective length' of 147 bp. As we have found previously with stretching around
      two turns from the nucleosome center for a centromere-based sequence, the
      terminal stretching observed in the 601 constructs is associated with extreme
      kinking into the minor groove at purine-purine (pyrimidine-pyrimidine)
      dinucleotide steps. In other contexts, these step types display an overall
      nonflexible behavior, which raises the possibility that DNA stretching in the
      nucleosome or extreme distortions in general have unique sequence dependency
      characteristics. Our findings indicate that DNA stretching is an intrinsically
      predisposed site-specific property of the nucleosome and suggest how NCP crystal
      structures with diverse DNA sequences can be obtained.

PMID- 20800599
TI  - Enhancer and competitive allosteric modulation model for G-protein-coupled
      receptors.
AB  - A new mathematical model, referred to as Enhancer and Competitive Allosteric
      Modulator (ECAM) model, developed with the aim of quantitatively describing the
      interaction of an allosteric modulator with both enhancer and competitive
      properties towards G-protein-coupled receptors is described here. Model
      simulations for equilibrium (displacement-like and saturation-like), and kinetic
      (association and dissociation) binding experiments were performed. The results
      showed the ability of the model to interpret a number of possible ligand-receptor
      binding behaviors. In particular, the binding properties of PD81723, an enhancer
      and competitive allosteric modulator for the adenosine A(1) receptor, were
      experimentally evaluated by radioligand binding assays and interpreted by the
      ECAM model. The results also offer a theoretical background enabling the design
      and optimization of compounds endowed with allosteric enhancer, competitive,
      agonist, antagonist, and inverse agonist properties.

PMID- 20800600
TI  - Pollinator coupling can induce synchronized flowering in different plant species.
AB  - Synchronous and intermittent plant reproduction has been identified widely in
      diverse biomes. While synchronous flowering is normally observed within the same
      species, different species also flower in synchrony. A well-known example of
      interspecific synchrony is "general flowering" in tropical rain forests of
      Southeast Asia. Environmental factors, such as low temperature and drought, have
      been considered as major trigger of general flowering. However, environmental
      cues are not enough to explain general flowering because some trees do not flower
      even when they encounter favorable environmental cues. We propose alternative
      explanation of general flowering; "pollinator coupling". When species flower
      synchronously, the elevated pollen and nectar resource may attract increased
      numbers of generalist pollinators, with a concomitant enhancement of pollination
      success (facilitation). However, under these circumstances, plants of different
      species may compete with one another for limited pollinator services, resulting
      in declines in pollination success for individual species (competition). Here, we
      present a model describing resource dynamics of individual trees serviced by
      generalist pollinators. We analyze combinations of conditions under which plants
      reproduce intermittently with synchronization within species, and/or (sometimes)
      between different species. We show that plants synchronize flowering when the
      number of pollinators attracted to an area increases at an accelerating rate with
      increasing numbers of flowers. In this case, facilitation of flowering by
      different species exceeds the negative influence of interspecific plant
      competition. We demonstrate mathematically that co-flowering of different species
      occurs under a much narrower range of circumstances than intraspecific co
      flowering.

PMID- 20800601
TI  - A two level mutation-selection model of cultural evolution and diversity.
AB  - Cultural evolution is a complex process that can happen at several levels. At the
      level of individuals in a population, each human bears a set of cultural traits
      that he or she can transmit to its offspring (vertical transmission) or to other
      members of his or her society (horizontal transmission). The relative frequency
      of a cultural trait in a population or society can thus increase or decrease with
      the relative reproductive success of its bearers (individual's level) or the
      relative success of transmission (called the idea's level). This article presents
      a mathematical model on the interplay between these two levels. The first aim of
      this article is to explore when cultural evolution is driven by the idea's level,
      when it is driven by the individual's level and when it is driven by both. These
      three possibilities are explored in relation to (a) the amount of interchange of
      cultural traits between individuals, (b) the selective pressure acting on
      individuals, (c) the rate of production of new cultural traits, (d) the
      individual's capacity to remember cultural traits and to the population size. The
      aim is to explore the conditions in which cultural evolution does not lead to a
      better adaptation of individuals to the environment. This is to contrast the
      spread of fitness-enhancing ideas, which make individual bearers better adapted
      to the environment, to the spread of "selfish" ideas, which spread well simply
      because they are easy to remember but do not help their individual bearers (and
      may even hurt them). At the same time this article explores in which conditions
      the adaptation of individuals is maximal. The second aim is to explore how these
      factors affect cultural diversity, or the amount of different cultural traits in
      a population. This study suggests that a larger interchange of cultural traits
      between populations could lead to cultural evolution not improving the adaptation
      of individuals to their environment and to a decrease of cultural diversity.

PMID- 20800602
TI  - Formulas for intrinsic noise evaluation in oscillatory genetic networks.
AB  - The linear noise approximation is a useful method for stochastic noise
      evaluations in genetic regulatory networks, where the covariance equation
      described as a Lyapunov equation plays a central role. We discuss the linear
      noise approximation method for evaluations of an intrinsic noise in autonomously
      oscillatory genetic networks; in such oscillatory networks, the covariance
      equation becomes a periodic differential equation that provides generally an
      unbounded covariance matrix, so that the standard method of noise evaluation
      based on the covariance matrix cannot be adopted directly. In this paper, we
      develop a new method of noise evaluation in oscillatory genetic networks; first,
      we investigate structural properties, e.g., orbital stability and periodicity, of
      the solutions to the covariance equation given as a periodic Lyapunov
      differential equation by using the Floquet-Lyapunov theory, and propose a global
      measure for evaluating stochastic amplitude fluctuations on the periodic
      trajectory; we also derive an evaluation formula for the period fluctuation.
      Finally, we apply our method to a model of circadian oscillations based on
      negative auto-regulation of gene expression, and show validity of our method by
      comparing the evaluation results with stochastic simulations.

PMID- 20800603
TI  - Investigation of genetic susceptibility factors for human longevity - a targeted
      nonsynonymous SNP study.
AB  - Twin studies have shown that longevity in humans is moderately heritable with a
      genetic component of 25-32%. Experimental model organisms point to the existence
      of core survival and anti-ageing pathways that have been conserved throughout
      evolution. It has been shown that mutations in single genes involved in these
      pathways can either delay or accelerate the ageing process and that many of these
      genes and pathways are also present in humans. Here, we performed a targeted
      investigation of selected genes (i) involved in longevity pathways (insulin
      receptor/insulin-like growth factor-I signaling and energy metabolism,
      intracellular signaling, apoptosis and stress response) and (ii) in which
      mutations lead to genetic perturbations in animal models or human diseases.
      Altogether, we tested 500 nonsynonymous single nucleotide polymorphisms (SNPs) in
      343 candidate genes for association with the longevity phenotype in a German
      sample comprising about 400 centenarians and an equal number of younger control
      subjects. Thus, this study presents one of the largest candidate studies in human
      genetic longevity research conducted to-date. The three top-ranking markers,
      which are located in the genes DUSP6, NALP1 and PERP, revealed p-values<=0.01 in
      the allelic case-control comparisons. Although the association signals in Germans
      were not replicated in an independent French sample, the large number of analysis
      results is deemed a valuable reference point for further genetic studies.

PMID- 20800604
TI  - Occupation attributes relate to location of atrophy in frontotemporal lobar
      degeneration.
AB  - Frontotemporal lobar degeneration (FTLD) often presents with asymmetric atrophy.
      We assessed whether premorbid occupations in FTLD patients were associated with
      these hemispheric asymmetries. In a multi-center chart review of 588 patients,
      occupation information was related to location of tissue loss or dysfunction.
      Patients with atrophy lateralized to the right had professions more dependent on
      verbal abilities than patients with left-lateralized or symmetrical atrophy. In a
      subgroup of 96 well-characterized patients with quantified neuroimaging data, the
      lateralization effect was localized to the temporal lobes and included verbal and
      mathematical ability. Patients whose professions placed high demands on language
      and mathematics had relatively preserved left temporal relative to right temporal
      volumes. Thus, occupation selection occurring in early adulthood is related to
      lateralized brain asymmetry in patients who develop FTLD decades later in the
      relatively deficient hemisphere. The finding suggests that verbal and
      mathematical occupations may have been pursued due to developmental right
      lateralized functional impairment that precedes the neurodegenerative process.
      Alternatively, long-term engagement of activities associated with these
      occupations contributed to left-lateralized reserve, right-lateralized
      dysfunction, or both.

PMID- 20800606
TI  - Uptake and cytotoxic effects of multi-walled carbon nanotubes in human bronchial
      epithelial cells.
AB  - Carbon nanotubes (CNT) are cytotoxic to several cell types. However, the
      mechanism of CNT toxicity has not been fully studied, and dosimetric analyses of
      CNT in the cell culture system are lacking. Here, we describe a novel, high
      throughput method to measure cellular uptake of CNT using turbimetry. BEAS-2B, a
      human bronchial epithelial cell line, was used to investigate cellular uptake,
      cytotoxicity, and inflammatory effects of multi-walled CNT (MWCNT). The
      cytotoxicity of MWCNT was higher than that of crocidolite asbestos in BEAS-2B
      cells. The IC(50) of MWCNT was 12 MUg/ml, whereas that of asbestos (crocidolite)
      was 678 MUg/ml. Over the course of 5 to 8 h, BEAS-2B cells took up 17-18% of the
      MWCNT when they were added to the culture medium at a concentration of 10 MUg/ml.
      BEAS-2B cells were exposed to 2, 5, or 10 MUg/ml of MWCNT, and total RNA was
      extracted for cytokine cDNA primer array assays. The culture supernatant was
      collected for cytokine antibody array assays. Cytokines IL-6 and IL-8 increased
      in a dose dependent manner at both the mRNA and protein levels. Migration
      inhibitory factor (MIF) also increased in the culture supernatant in response to
      MWCNT. A phosphokinase array study using lysates from BEAS-2B cells exposed to
      MWCNT indicated that phosphorylation of p38, ERK1, and HSP27 increased
      significantly in response to MWCNT. Results from a reporter gene assays using the
      NF-kappaB or AP-1 promoter linked to the luciferase gene in transiently
      transfected CHO-KI cells revealed that NF-kappaB was activated following MWCNT
      exposure, while AP-1 was not changed. Collectively, MWCNT activated NF-kappaB,
      enhanced phosphorylation of MAP kinase pathway components, and increased
      production of proinflammatory cytokines in human bronchial epithelial cells.

PMID- 20800605
TI  - An analysis of the effects of Mn2+ on oxidative phosphorylation in liver, brain,
      and heart mitochondria using state 3 oxidation rate assays.
AB  - Manganese (Mn) toxicity is partially mediated by reduced ATP production. We have
      used oxidation rate assays--a measure of ATP production--under rapid
      phosphorylation conditions to explore sites of Mn(2+) inhibition of ATP
      production in isolated liver, brain, and heart mitochondria. This approach has
      several advantages. First, the target tissue for Mn toxicity in the basal ganglia
      is energetically active and should be studied under rapid phosphorylation
      conditions. Second, Mn may inhibit metabolic steps which do not affect ATP
      production rate. This approach allows identification of inhibitions that decrease
      this rate. Third, mitochondria from different tissues contain different amounts
      of the components of the metabolic pathways potentially resulting in different
      patterns of ATP inhibition. Our results indicate that Mn(2+) inhibits ATP
      production with very different patterns in liver, brain, and heart mitochondria.
      The primary Mn(2+) inhibition site in liver and heart mitochondria, but not in
      brain mitochondria, is the F1F0 ATP synthase. In mitochondria fueled by either
      succinate or glutamate+malate, ATP production is much more strongly inhibited in
      brain than in liver or heart mitochondria; moreover, Mn(2+) inhibits two
      independent sites in brain mitochondria. The primary site of Mn-induced
      inhibition of ATP production in brain mitochondria when succinate is substrate is
      either fumarase or complex II, while the likely site of the primary inhibition
      when glutamate plus malate are the substrates is either the glutamate/aspartate
      exchanger or aspartate aminotransferase.

PMID- 20800607
TI  - Sub-lethal dosing of azaspiracid-1 in female NMRI mice.
AB  - The main aim of this study was to examine absorption and pathological effects of
      a single sub-lethal dose of the marine biotoxin azaspiracid-1 (AZA1) in mice
      after oral intubation. When the mice received AZA1 at doses of 100, 200 or 300
      MUg/kg body weight (b.w.), the toxin was absorbed dose-dependently. Highest
      concentrations after 24 h were detected in kidneys, spleen and lungs, followed by
      liver and heart. Only trace amounts were seen in the brain. After seven days, the
      toxin level had dropped significantly in all organs except for the kidneys. The
      amount of toxin absorbed was highest in the liver, followed by kidneys, lungs,
      spleen and heart and the total amount of toxin in the internal organs analysed
      after 24 h was estimated to be only about 2% of the total amount given for all
      three dose groups. Pathological changes were only detected in the upper part of
      the small intestine (duodenum), consisting of mild cellular detachment in the
      tips of the villi, expansion of the crypts and necrotic changes in lamina
      propria. In a previous study very long persistence of damage to the
      gastrointestinal tract by repeated exposures to AZA toxins was reported. In our
      study, full recovery from the pathological changes was observed seven days after
      a single exposure to AZA1 at the doses applied.

PMID- 20800608
TI  - Young without plastic surgery: perceptual adaptation to the age of female and
      male faces.
AB  - Adaptation influences perception not only of simple stimulus qualities such as
      motion or colour, but also of complex stimuli such as faces. Here we demonstrate
      contrasting aftereffects of adaptation to facial age. In Experiment 1,
      participants adapted to either young or old faces, and subsequently estimated the
      age of morphed test faces with interpolated ages of 30, 40, 50 or 60 years.
      Following adaptation to old adaptors, test faces were classified as much younger
      when compared to classifications of the same test faces following adaptation to
      young faces, which in turn caused subjective test face "aging". These
      aftereffects were reduced but remained clear even when facial gender changed
      between adaptor and test faces. In Experiment 2, we induced simultaneous opposite
      age aftereffects for female and male faces. Overall, these results demonstrate
      interactions in the perception of facial age and gender, and support dissociable
      neuronal coding of male and female faces.

PMID- 20800609
TI  - Contribution of post-receporal cells to the cone a-wave of the human
      electroretinogram in congenital stationary night blindness and autoimmune-like
      retinopathy.
AB  - In normal subjects the later part of the cone a-wave to a brief flash increases
      in amplitude after 50-100 ms darkness due to a contribution from secondary
      hyperpolarising cells. We recorded these responses along with clinical ON and OFF
      ERGs in patients with inner retinal dysfunction to see if this part of the a-wave
      is affected. Patients with autoimmune-like retinopathy and CSNB2 had abnormal ON
      and OFF responses but the a-wave increased in amplitude in the dark as in
      normals. Conversely, the OFF-response was normal in CSNB1 but the a-wave did not
      increase in the dark. Contrary to expectation these results show some
      hyperpolarising cell function in autoimmune-like disease and CSNB2 and some OFF
      pathway abnormality in CSNB1. The a- and d-wave are needed to assess OFF-pathway
      function.

PMID- 20800610
TI  - Biological motion influences the visuomotor transformation for smooth pursuit eye
      movements.
AB  - Humans are very sensitive to the presence of other living persons or animals in
      their surrounding. Human actions can readily be perceived, even in a noisy
      environment. We recently demonstrated that biological motion, which schematically
      represents human motion, influences smooth pursuit eye movements during the
      initiation period (Orban de Xivry, Coppe, Lefevre, & Missal, 2010). This smooth
      pursuit response is driven both by a visuomotor pathway, which transforms retinal
      inputs into motor commands, and by a memory pathway, which is directly related to
      the predictive properties of smooth pursuit. To date, it is unknown which of
      these pathways is influenced by biological motion. In the present study, we first
      use a theoretical model to demonstrate that an influence of biological motion on
      the visuomotor and memory pathways might both explain its influence on smooth
      pursuit initiation. In light of this model, we made theoretical predictions of
      the possible influence of biological motion on smooth pursuit during and after
      the transient blanking of the stimulus. These qualitative predictions were then
      compared with recordings of eye movements acquired before, during and after the
      transient blanking of the stimulus. The absence of difference in smooth pursuit
      eye movements during blanking of the stimuli and the stronger visually guided
      smooth pursuit reacceleration after reappearance of the biological motion stimuli
      in comparison with control stimuli suggests that biological motion influences the
      visuomotor pathway but not the memory pathway.

PMID- 20800611
TI  - Lateral facilitation--no effect on the target noise level.
AB  - The detection threshold of a centrally placed Gabor target is reduced in the
      presence of aligned high-contrast Gabor patches that are optimally spaced from
      the target (Polat & Sagi, 1993). Here we determined whether threshold reduction
      is due to signal enhancement or to decreased signal response variability
      (internal noise), using a recently developed analysis for a Signal Detection
      Theory (SDT)-based contrast-identification paradigm (Katkov, Tsodyks, & Sagi,
      2007a). We found that flankers did not affect internal noise, but instead caused
      increased target response when collinear with it, in agreement with the lateral
      facilitation effect. Based on these results, we concluded that lateral
      facilitation can be explained by signal enhancement only, and that uncertainty
      based models do not provide a satisfactory description of the data.

PMID- 20800612
TI  - Biomaterials based on new polyurethane and hydrolyzed collagen, k-elastin,
      hyaluronic acid and chondroitin sulfate.
AB  - In this paper biomaterials based on various polyurethane formulations have been
      physically characterized by FT-IR spectroscopy, contact angle measurements, DSC,
      TG/DTG and SEM methods. It has been established that the transition temperatures
      of soft and hard segments of polyurethane (glass transition or melting) depend on
      the blend composition. The melting temperature varies from 54.2 to 81.9 degrees C
      for soft segments, and from 220 to 235 degrees C for hard segments. FT-IR
      spectrometry allows identifying the functional groups involved in interactions
      and consequently the changes in polymer chain mobility. From SEM images, is
      evident that polyurethanic film is porous and spongious. By adding of the others
      components such as hydrolyzed collagen, elastin, chondroitin sulfate or
      hyaluronic acid, a reduction of porosity of films was obtained.

PMID- 20800613
TI  - Global trends and performances of acupuncture research.
AB  - This study was designed to evaluate the global scientific output of acupuncture
      research in the Science Citation Index-Expanded and to assess the tendencies and
      research performances of leading countries/territories and institutes. Articles
      referring to acupuncture were assessed by distribution of document types,
      languages, journals, subject categories, source countries, and source institutes.
      Results showed that 15 languages were represented in articles from 65
      countries/territories. Journal of Alternative and Complementary Medicine
      published the most articles, followed by American Journal of Chinese Medicine and
      Acupuncture & Electro-Therapeutics Research which were listed in category of
      integrative & complementary medicine. In the study period of 1991-2009, USA was
      the top producing country, followed by China (mainland) with a sharply growth
      trend. In 2009, publication of China (mainland) ranked top one in the world. In
      addition, an acupuncture research trend was found in two phases in terms of the
      increase of number of SCI-expanded journals' articles. Among the acupuncture
      research, pain control has been the most prevalent direction of study, and brain
      imaging is attracting the most recent attention.

PMID- 20800614
TI  - Potential animal models of seasonal affective disorder.
AB  - Seasonal affective disorder (SAD) is characterized by depressive episodes during
      winter that are alleviated during summer and by morning bright light treatment.
      Currently, there is no animal model of SAD. However, it may be possible to use
      rodents that respond to day length (photoperiod) to understand how photoperiod
      can shape the brain and behavior in humans. As nights lengthen in the autumn, the
      duration of the nightly elevation of melatonin increase; seasonally breeding
      animals use this information to orchestrate seasonal changes in physiology and
      behavior. SAD may originate from the extended duration of nightly melatonin
      secretion during fall and winter. These similarities between humans and rodents
      in melatonin secretion allows for comparisons with rodents that express more
      depressive-like responses when exposed to short day lengths. For instance,
      Siberian hamsters, fat sand rats, Nile grass rats, and Wistar rats display a
      depressive-like phenotype when exposed to short days. Current research in
      depression and animal models of depression suggests that hippocampal plasticity
      may underlie the symptoms of depression and depressive-like behaviors,
      respectively. It is also possible that day length induces structural changes in
      human brains. Many seasonally breeding rodents undergo changes in whole brain and
      hippocampal volume in short days. Based on strict validity criteria, there is no
      animal model of SAD, but rodents that respond to reduced day lengths may be
      useful to approximate the neurobiological phenomena that occur in people with
      SAD, leading to greater understanding of the etiology of the disorder as well as
      novel therapeutic interventions.

PMID- 20800617
TI  - Transcriptome profiling in neurodegenerative disease.
AB  - Changes in gene expression and splicing patterns (that occur prior to the onset
      and during the progression of complex diseases) have become a major focus of
      neurodegenerative disease research. These signature patterns of gene expression
      provide clues about the mechanisms involved in the molecular pathogenesis of
      neurodegenerative disease and may facilitate the discovery of novel therapeutic
      drugs. With the development of array technologies and the very recent RNA-seq
      technique, our understanding of the pathogenesis of neurodegenerative disease is
      expanding exponentially. Here, we review the technologies involved in gene
      expression and splicing analysis and the related literature on three common
      neurodegenerative diseases: Alzheimer's disease, Parkinson's disease and
      Huntington's disease.

PMID- 20800616
TI  - MDMA administration decreases serotonin but not N-acetylaspartate in the rat
      brain.
AB  - In animals, repeated administration of 3,4-methylenedioxymethamphetamine (MDMA)
      reduces markers of serotonergic activity and studies show similar serotonergic
      deficits in human MDMA users. Using proton-magnetic resonance spectroscopy ((1)H
      MRS) at 11.7Tesla, we measured the metabolic neurochemical profile in intact,
      discrete tissue punches taken from prefrontal cortex, anterior striatum, and
      hippocampus of rats administered MDMA (5mg/kg IP, 4* q 2h) or saline and
      euthanized 7 days after the last injection. Monoamine content was measured with
      HPLC in contralateral punches from striatum and hippocampus to compare the MDMA
      induced loss of 5HT innervation with constituents in the (1)H-MRS profile. When
      assessed 7 days after the last MDMA injection, levels of hippocampal and striatal
      serotonin (5HT) were significantly reduced, consistent with published animal
      studies. N-Acetylaspartate (NAA) levels were significantly increased in
      prefrontal cortex and not affected in anterior striatum or hippocampus; myo
      inositol (INS) levels were increased in prefrontal cortex and hippocampus but not
      anterior striatum. Glutamate levels were increased in prefrontal cortex and
      decreased in hippocampus, while GABA levels were decreased only in hippocampus.
      The data suggest that NAA may not reliably reflect MDMA-induced 5HT
      neurotoxicity. However, the collective pattern of changes in 5HT, INS, glutamate
      and GABA is consistent with persistent hippocampal neuroadaptations caused by
      MDMA.

PMID- 20800618
TI  - Remote switching of temperature, gaseous, and aqueous phase in a low-volume
      interface chamber for brain slices.
AB  - A new remote-controlled interface-type chamber was designed in order to conduct
      experiments in brain slices involving gas, fluid, and temperature changes with as
      little tissue manipulation as possible. The chamber allows for extremely quick
      changes between different fluid and/or gaseous phases and for active cooling as
      well as heating by using a set of electromechanical valves and Peltier elements.
      The design drawings are complemented by exemplary tests of temperature and gas
      changes, and electrophysiological recordings of slices manipulated with gas and
      fluid alterations were used to test the efficacy and accuracy of the design.
      Changing between normoxia and anoxia needs less than 30 s, while the readjustment
      of the chamber to a new, preset temperature is accomplished in about 1 min.
      Supplementary data provide a proposal for the electronic circuit diagram. This
      chamber design should simplify data acquisition in interface environments.

PMID- 20800619
TI  - Facial affect processing in social anxiety: tasks and stimuli.
AB  - Social anxiety (SA) has as its main feature the fear of social situations, being
      characterized as social phobia or social anxiety disorder when functional
      impairment emerges as a result of that fear. Although the recognition of the
      condition has increased in recent years, it is believed that many patients and
      physicians still take the symptoms of the disorder for personality traits with no
      need for treatment. There is evidence that people with SA display abnormal
      patterns of facial emotion processing that could account for the onset and
      maintenance of the disorder. The objective of this review is to describe,
      compare, and discuss the methods used to study facial emotion processing in SA
      with an emphasis on the tasks and stimuli employed. Articles were searched for on
      online scientific databases. Forty research articles were selected according to
      the inclusion and exclusion criteria established. The articles were read and
      information from them was gathered on a comparative table for analysis. Evidence
      available to date suggests that SA individuals have abnormal patterns of facial
      information processing characterized by a bias for negative emotions. The results
      of the articles analyzed have a high degree of concordance, in spite of the
      variety of tasks and stimuli employed. The similarity between results from non
      clinical samples with SA and patients affected by social phobia speaks in favor
      of the current view that SA occurs as a continuum of severity, rather than a
      clearly circumscribed nosological entity.

PMID- 20800615
TI  - Sniffing out the contributions of the olfactory tubercle to the sense of smell:
      hedonics, sensory integration, and more?
AB  - Since its designation in 1896 as a putative olfactory structure, the olfactory
      tubercle has received little attention in terms of elucidating its role in the
      processing and perception of odors. Instead, research on the olfactory tubercle
      has mostly focused on its relationship with the reward system. Here we provide a
      comprehensive review of research on the olfactory tubercle-with an emphasis on
      the likely role of this region in olfactory processing and its contributions to
      perception. Further, we propose several testable hypotheses regarding the likely
      involvement of the olfactory tubercle in both basic (odor detection,
      discrimination, parallel processing of olfactory information) and higher-order
      (social odor processing, hedonics, multi-modal integration) functions. Together,
      the information within this review highlights an understudied yet potentially
      critical component in central odor processing.

PMID- 20800620
TI  - Performance of juvenile mice in a reach-to-grasp task.
AB  - Reach-to-grasp tasks have been used to study rodent models of motor system
      damage, stroke, and neurodegenerative disorders such as Parkinson's. These tasks
      are especially useful as they allow evaluation of bilateral or unilateral damage
      in different regions of the brain. Performing reach-to-grasp tests in juvenile
      mice may be important to understand motor disorders of early onset. This study
      evaluated the performance of juvenile and adolescent mice on a reach-to-grasp
      task. Male and female C57BL/6J mice (n=93) were tested in a forelimb reaching
      task at postnatal weeks 4, 5, 7, 9 and 12. At all ages mice could learn the task
      and improved performance with training. Results show that reach-to-grasp tasks
      can be used to study skill learning in juvenile and adolescent mice. Results are
      discussed in terms of adapting methodologies (test protocols and arenas) when
      performing behaviour tests in young mice.

PMID- 20800621
TI  - Comparison of NT-proCNP and CNP plasma levels in heart failure, diabetes and
      cirrhosis patients.
AB  - C-type natriuretic peptide (CNP) plasma levels are extremely low and a pre
      analytical phase is necessary to assay plasma CNP concentrations. Amino-terminal
      CNP (NT-proCNP) circulates at higher concentrations than CNP, allowing a direct
      assay and the use of smaller amounts of plasma. Aim of this study was to evaluate
      the analytical performance of a direct NT-proCNP assay and to measure its plasma
      levels in heart failure (CHF), diabetes and chirrosis patients. NT-proCNP and CNP
      were measured in 130 CHF, 19 patients with diabetes, 24 with hepatic cirrhosis
      and 73 controls. Plasma NT-proCNP was higher in all the clinical conditions
      studied (controls:45.5 +/- 1.84 pg/ml, CHF:67.09 +/- 7.36, diabetes:51.5 +/- 5.75
      cirrhosis:78.4 +/- 19.9; p = 0.034, p = 0.04 controls vs. CHF and cirrhosis,
      respectively) and in CHF NT-proCNP concentration showed a significant increase as
      a function of clinical severity. By comparison of ROC curves, CNP assay resulted
      better associated with disease than NT-proCNP assay in all the different clinical
      conditions probably due to different release and clearance. The determination of
      NT-proCNP adds a piece of information to better understanding the molecular
      mechanisms at the basis of CNP action in different diseases. Due to its higher
      analytical feasibility, this determination could become widespread in clinical
      biochemistry laboratories and serve as a complementary marker of disease
      conditions.

PMID- 20800622
TI  - Etoposide induces apoptosis and upregulation of TACE/ADAM17 and ADAM10 in an in
      vitro male germ cell line model.
AB  - Etoposide is a widely used anticancer drug in the treatment of different tumors.
      Etoposide is known to activate a wide range of intracellular signals, which may
      in turn induce cellular responses other than apoptosis. ADAM10 and TACE/ADAM17
      belong to a family of transmembrane extracellular metalloproteinases involved in
      paracrine/juxtacrine regulation of many signaling pathways. The aim of this work
      was to evaluate if etoposide induces upregulation of ADAM10 or TACE/ADAM17 in two
      cell lines (GC-1 and GC-2) derived from male germ cells. Results showed that
      etoposide induced apoptosis in a dose-response manner in both GC-1 and GC-2
      cells. Apoptosis started to increase 6h after etoposide addition in GC-2 cells,
      whereas the same was observed 18h after addition to the GC-1 cells. Protein and
      mRNA levels of ADAM10 and TACE/ADAM17 increased 18h after etoposide was removed
      from the GC-1 cells. In GC-2 cells, the protein levels of both proteins increased
      12h after etoposide was removed. ADAM10 mRNA increased after 3h and then steadily
      decreased up to 12h after removal, whereas TACE/ADAM17 mRNA decreased after
      etoposide removal. Finally, apoptosis was prevented in GC-1 and GC-2 cells by the
      addition of pharmacological inhibitors of ADAM10 and TACE/ADAM17 to the culture
      medium of etoposide-treated cells. Our results show for the first time that
      etoposide upregulates ADAM10 and TACE/ADAM17 mRNA and protein levels. In
      addition, we also show that ADAM10 and TACE/ADAM17 have a role in etoposide
      induced apoptosis.

PMID- 20800623
TI  - Processing of visual stimuli in borderline personality disorder: a combined
      behavioural and magnetoencephalographic study.
AB  - BACKGROUND: Behavioral studies on facial emotion recognition yielded
      heterogeneous results in patients with Borderline Personality Disorder (BPD).
      Extrastriate cortex hyperactivation has been demonstrated in imaging studies in
      patients with BPD during face recognition, but electrophysiological studies are
      lacking. The aim was to investigate temporal processes following face perception
      in patients with BPD. METHODS: Magnetoencephalography (MEG) was used in eleven
      non-medicated patients with BPD and nine age-matched healthy subjects. Behavioral
      responses to visual stimuli and an emotion discrimination task were evaluated.
      First, participants had to silently watch faces, houses and animals. Emotional
      expressive faces then had to be judged from two basic emotions in a two
      alternative forced choice task. Regional field power (RFP) of MEG signals was
      obtained from two regions of interest: Temporal and occipital areas. Psychometric
      assessment was performed. RESULTS: Patients with BPD had significantly reduced
      RFP amplitudes in the right posterior occipital region of interest, for the time
      window between 150 and 160 ms, irrespective of the type of visual stimulus or the
      emotional face category. Patients with BPD had significantly higher error rates
      for recognition of emotional expressive faces compared to healthy controls though
      they showed a higher accuracy in detecting fearful faces. Controls improved
      during face recognition, whereas patients showed no learning effect. CONCLUSION:
      This MEG study provides evidence for disturbances in cortical visual perception
      in BPD patients regardless of emotional salience of the stimulus. In line with
      previous studies subtle deficits in visual perception might be related to
      impairment in interpersonal communication in BPD.

PMID- 20800624
TI  - The effect of stimulus expectancy on dishabituation of auditory evoked
      potentials.
AB  - OBJECTIVES: Having foreknowledge of the type and timing of sensory stimulation
      modulates the electrophysiological response and can result in short-term
      habituation. Here we explore if dishabituation is similarly affected. METHODS:
      Seventeen healthy subjects were tested with five different auditory stimuli
      paradigms to see if knowledge of the stimulus train length and/or deviant
      stimulus affects the amount of dishabituation of auditory evoked potentials.
      Furthermore it was determined if the degree of difference between the repeating
      stimulus and deviant stimulus affected the amount of dishabituation. RESULTS:
      Stimulus complexity is the main determinant of the degree of dishabituation,
      followed by lack of knowledge about train length. Not knowing the deviant
      stimulus has little or no effect on dishabituation. Also, P200 is the most
      affected by expectancy and P50 not at all. CONCLUSIONS: Foreknowledge of the type
      and timing of sensory stimulation modulates the degree of dishabituation.
      SIGNIFICANCE: Previous reports have shown that expectancy does affect (certain)
      evoked potential components. Here we extend this knowledge to the effect of
      expectancy on dishabituation.

PMID- 20800625
TI  - Modulation of cortically induced rhythmic jaw movements in rats by stimulation of
      the vestibular nuclear complex.
AB  - We study whether stimulation of the vestibular nuclear (VN) complex can modulate
      rhythmic jaw movements in rats anesthetized by urethane. Rhythmic jaw movements
      were induced by repetitive electrical stimulation of the orofacial motor cortex.
      Stimulation of the medial vestibular nucleus (MVN) during the jaw-closing phase
      increased the amplitude of the jaw-closing movement. (This is not a movement that
      continues to closure.) Stimulation of the MVN during the jaw-opening phase
      disturbed the rhythm of jaw movements and induced a small jaw-closing movement.
      Stimulation of the superior VN (SVN) and the lateral VN (LVN) during the jaw
      closing phase did not affect the amplitude of the jaw-closing movement.
      Stimulation of the SVN and the LVN during the jaw-opening phase increased the
      amplitude of the jaw-opening movement, however. Stimulation of the inferior VN
      during the jaw-closing and the jaw-opening phase, respectively decreased the
      amplitude of the jaw-closing and the jaw-opening movements. Stimulation applied
      outside the VN did not modulate the amplitude of the jaw movements. These results
      imply that the VN is involved in the modulation of rhythmic jaw movements induced
      by stimulation of the orofacial motor cortex.

PMID- 20800626
TI  - Evaluation of the effect of pyrimethamine, an anti-malarial drug, on HIV-1
      replication.
AB  - Co-infection of human immunodeficiency virus (HIV) with malaria is one of the
      pandemic problems in Africa and parts of Asia. Here we investigated the impact of
      pyrimethamine (PYR) and two other clinical anti-malarial drugs (chloroquine [CQ]
      or artemisinin [ART]) on HIV-1 replication. Peripheral blood mononuclear cells
      (PBMCs) or MT-2 cells were infected with HIV(NL4.3) strain and treated with
      different concentrations of the anti-malarial drugs. HIV-1 replication was
      measured using p24 ELISA. We show that 10 MUM CQ and ART inhibited HIV-1
      replication by 76% and 60% in PBMCs, respectively, but not in MT-2 cells. In
      contrast, 10 MUM PYR enhanced HIV-1 replication in MT-2 cells by >10-fold. A
      series of molecular mechanism studies revealed that PYR increased intracellular
      HIV gag proteins without affecting the promoter or the reverse transcriptase
      activity. The effect of PYR was independent of HTLV-1 produced by MT-2 cells. Of
      interest, PYR treatment led to S-phase accumulation and increased AZT and d4T
      antiviral activity by ~ 4-fold. Taken together, we show that PYR significantly
      enhances HIV-1 replication by affecting the cellular machinery. Our results could
      be relevant for the management of malaria and HIV particularly in regions where
      HIV-1 and malaria epidemics overlap.

PMID- 20800627
TI  - SARS-coronavirus protein 6 conformations required to impede protein import into
      the nucleus.
AB  - The severe acute respiratory syndrome coronavirus (SARS-CoV) genome encodes eight
      accessory proteins. Accessory protein 6 is a 63-residue amphipathic peptide that
      accelerates coronavirus infection kinetics in cell culture and in mice. Protein 6
      is minimally bifunctional, with an N-terminal lipophilic part implicated in
      accelerating viral growth and a C-terminal hydrophilic part interfering with
      general protein import into the nucleus. This interference with nuclear import
      requires interaction between protein 6 and cellular karyopherins, a process that
      typically involves nuclear localization signal (NLS) motifs. Here we dissected
      protein 6 using site-directed mutagenesis and found no evidence for a classical
      NLS. Furthermore, we found that the C-terminal tail of protein 6 impeded nuclear
      import only in the context of a lipophilic N-terminus, which could be derived
      from membrane proteins unrelated to protein 6. These findings are discussed in
      the context of the proposed protein 6 structure.

PMID- 20800628
TI  - RVG peptide tethered bioreducible polyethylenimine for gene delivery to brain.
AB  - The work demonstrated the successful delivery of gene to mouse brain overcoming
      the blood-brain barrier (BBB) through expedient vector construct having RVG
      peptide as targeting ligand for neuronal cells. The newly developed delivery
      vector was designed to impart bioreducibility for greater intracellular pDNA
      release, higher serum stability and efficient complexing ability by incorporating
      disulfide linkage, PEG and low molecular weight polyethylenimine, respectively.
      The physiochemical properties of the polyplex, its cytotoxicity and the in vitro
      transfection efficiency on Neuro2a cell were studied prior to the successful in
      vivo study. In vivo fluorescence assay substantiated the permeation of the pDNA
      loaded polymeric vector through the BBB. The RVG-mediated target-specific
      cellular uptake of polymeric vector was established conclusively by competitive
      assay.

PMID- 20800629
TI  - Peritoneal retention of liposomes: Effects of lipid composition, PEG coating and
      liposome charge.
AB  - In the treatment of peritoneal carcinomatosis, systemic chemotherapy is not quite
      effective due to the poor penetration of cytotoxic agents into the peritoneal
      cavity, whereas intraperitoneal administration of chemotherapeutic agents is
      generally accompanied by quick absorption of the free drug from the peritoneum.
      Local delivery of drugs with controlled-release delivery systems like liposomes
      could provide sustained, elevated drug levels and reduce local and systemic
      toxicity. In order to achieve an ameliorated liposomal formulation that results
      in higher peritoneal levels of the drug and retention, vesicles composed of
      different phospholipid compositions (distearoyl [DSPC]; dipalmitoyl [DPPC]; or
      dimiristoylphosphatidylcholine [DMPC]) and various charges (neutral; negative,
      containing distearoylphosphatidylglycerol [DSPG]; or positive, containing
      dioleyloxy trimethylammonium propane [DOTAP]) were prepared at two sizes of 100
      and 1000nm. The effect of surface hydrophilicity was also investigated by
      incorporating PEG into the DSPC-containing neutral and charged liposomes.
      Liposomes were labeled with (99m)Tc and injected into mouse peritoneum. Mice were
      then sacrificed at eight different time points, and the percentage of injected
      radiolabel in the peritoneal cavity and the tissue distribution in terms of the
      percent of the injected dose/gram of tissue (%ID/g) were obtained. The ratio of
      the peritoneal AUC to the free label ranged from a minimum of 4.95 for DMPC/CHOL
      (cholesterol) 100nm vesicles to a maximum of 24.99 for DSPC/CHOL/DOTAP 1000nm
      (DOTAP 1000) vesicles. These last positively charged vesicles had the greatest
      peritoneal level; moreover, their level remained constant at approximately 25% of
      the injected dose from 2 to 48h. Among the conventional (i.e., without PEG) 100nm
      liposomes, the positively charged vesicles again showed the greatest retention.
      Incorporation of PEG at this size into the lipid structures augmented the
      peritoneal level, particularly for negatively charged liposomes. The positively
      charged PEGylated vesicles (DOTAP/PEG 100) had the second-greatest peritoneal
      level after DOTAP 1000; however, their peritoneal-to-blood AUC ratio was low
      (3.05). Overall, among the different liposomal formulations, the positively
      charged conventional liposomes (100 and 1000nm) provided greater peritoneal
      levels and retention. DOTAP/PEG100 may also be a more efficient formulation
      because this formulation can provide a high level of anticancer drug into the
      peritoneal cavity and also can passively target the primary tumor.

PMID- 20800630
TI  - Adenovirus serotype 35 vector-induced innate immune responses in dendritic cells
      derived from wild-type and human CD46-transgenic mice: Comparison with a fiber
      substituted Ad vector containing fiber proteins of Ad serotype 35.
AB  - Recently, much attention has focused on replication-incompetent adenovirus (Ad)
      vectors containing fiber proteins derived from species B Ad serotype 35 (Ad35)
      (Ad5F35) and Ad vectors fully constructed from Ad35 as vaccine vectors expressing
      antigens. However, differences in the transduction properties, including the
      induction of innate immunity, of Ad5F35 and Ad35 vectors have not been properly
      and fully examined, partly because the transduction properties of these Ad
      vectors should be evaluated using nonhuman primates or human CD46-transgenic
      (CD46TG) mice, which ubiquitously express the primary receptor of Ad35, human
      CD46, in a pattern similar to that of humans. In the present study, we evaluated
      innate immune responses of mouse dendritic cells (mDCs) derived from bone marrow
      cells of wild-type (WT) and CD46TG mice following transduction with Ad serotype 5
      (Ad5), fiber-substituted Ad5F35, or Ad35 vectors. Ad5F35 and Ad35 vectors
      mediated more efficient transduction in mDCs derived from CD46TG mice (CD46TG
      mDCs) than did Ad5 vectors. Upregulation of costimulatory molecules and
      inflammatory cytokine induction by Ad5F35 and Ad35 vectors were significantly
      higher than those by Ad5 vectors in CD46TG-mDCs. However, the induction
      properties of the innate immune responses were different between Ad5F35 and Ad35
      vectors. Ad35 vectors induced higher levels of costimulatory molecule expression
      and inflammatory cytokine production than did Ad5F35 vectors in CD46TG-mDCs.
      Furthermore, intravenous administration of Ad35 vectors in WT and CD46TG mice
      resulted in higher levels of serum interleukin (IL)-6 and IL-12 compared with
      administration of Ad5F35 vectors, which exhibited almost mock-transduced levels
      of these inflammatory cytokines. This study indicates that innate immune
      responses by Ad35 and Ad5F35 vectors are distinct even although both Ad vectors
      recognize human CD46 as a receptor.

PMID- 20800631
TI  - Oligoarginine-linked polymers as a new class of penetration enhancers.
AB  - Oligoarginines, which are known as cell-penetrating peptides, enhance the
      cellular uptake of poorly membrane-permeable bioactive molecules that are
      chemically conjugated to them. We designed a novel polymer: oligoarginine-linked
      poly(N-vinylacetamide-co-acrylic acid), with the expectation that the polymers
      will enhance the cellular uptake of the bioactive molecules that are physically
      mixed with them. Oligoarginines were grafted onto the polymer backbone through
      the chemical reaction with acrylic acid functional groups. The changes in the
      blood glucose concentration after nasal administration of insulin with and
      without the polymer were monitored in mice. The blood glucose concentration was
      slightly reduced when insulin was given solely at a dose of 10IU/kg. A D
      octaarginine-linked poly(N-vinylacetamide-co-acrylic acid) with a grafting degree
      of 2% significantly enhanced the insulin-induced hypoglycemic effect. A similar
      enhancement was not observed when the polymer was substituted with intact D
      octaarginine. The penetration-enhancing function of D-octaarginine-linked poly(N
      vinylacetamide-co-acrylic acid) increased dramatically with an increase in the
      grafting degree of D-octaarginine. Substitution of D-octaarginine with the
      corresponding optical isomer and an increase in the number of arginine residues
      rather reduced the penetration-enhancing function. In vitro cell studies also
      indicated that a D-octaarginine-linked poly(N-vinylacetamide-co-acrylic acid)
      with a grafting degree of 17% enabled fluorescein isothiocyanate-dextran to
      effectively penetrate the cell membrane. Results demonstrated that our
      oligoarginine-linked polymer has a potential to provide a new class of
      penetration enhancers.

PMID- 20800632
TI  - Effects of nutritional supplementation on the appetite and energy intake
      responses to IV cholecystokinin in older adults.
AB  - Human aging is associated with a reduction in appetite and food intake. Increased
      activity of the satiety hormone, cholecystokinin (CCK), may be partly
      responsible. This study aimed to determine whether an increase in fat and energy
      intake modifies the suppressive effects of CCK-8 on appetite and energy intake.
      Fourteen healthy older adults completed three separate dietary periods, a 14-day
      and a 7-day normal diet (ND; 8272 +/- 480 kJ/day; 35% fat), and a 14-day high-fat
      diet (HFD; 11,642 +/- 414 kJ/day; 43% fat), in randomised order. Immediately
      following each diet, subjects received, in single-blinded fashion, a 30-min
      intravenous infusion of either CCK-8 (1.5 ng/kg/min) (ND-CCK, HFD-CCK) or 0.9%
      saline (ND-SAL), the latter following only ND. Plasma CCK concentrations,
      appetite responses and energy intake at a buffet meal were determined. Energy
      intake at the buffet meal was higher on the ND-SAL study day (3349 +/- 224 kJ),
      when compared with either ND-CCK (3023 +/- 317 kJ) or HFD-CCK (2905 +/- 316 kJ).
      The suppression of energy intake by CCK-8 infusion did not differ between the two
      diets. We conclude that suppression of energy intake by exogenous CCK-8 does not
      appear to be attenuated by incorporation of supplemental high-energy, high-fat
      drinks in the diet of healthy older adults.

PMID- 20800633
TI  - Effects of PACAP and VIP on hyperglycemia-induced proliferation in murine
      microvascular endothelial cells.
AB  - Hyperglycemia is implicated both in micro- and macro-vascular complications in
      diabetes mellitus. Pituitary adenylate cyclase-activating polypeptide (PACAP) and
      vasoactive intestinal polypeptide (VIP) are two known nonclassic regulators of
      angiogenesis, although their biological role on endothelial cell proliferation
      remains poorly defined. In the present study we hypothesized that either peptides
      might play an inhibitory role on hyperglycemia-induced cell growth. To this end,
      we investigated the effect of both PACAP and VIP on cell proliferation in murine
      microvascular endothelial cells (H5V) cultured both under euglycemic and
      hyperglycemic conditions (5 and 25 mM glucose, respectively) for 24, 48 h, 7 and
      15 days. Results demonstrated that high glucose treatment induced a time
      dependent increase in cell viability after 48 h (p<0.05), which was much more
      evident after 7 and 15 days (p<0.001). Similar effects were observed in cell
      proliferation, although significant changes were obtained after prolonged
      exposures to high glucose (7 and 15 days; p<0.001). The proliferative response to
      the glucose-enriched environment was correlated to changes in the expression of
      PAC1 and, to a minor extent, to VPAC2, but not VPAC1 receptors, as measured by
      quantitative real-time PCR. These results were further confirmed by Western blot
      and immunofluorescence analyses. Interestingly, 10-7 M PACAP or VIP treatment
      significantly attenuated hyperglycemia-induced increase in cell viability and
      proliferation after 7 and 15 days. Taken together, our findings demonstrate that
      both PACAP and VIP peptides exert an inhibitory activity on hyperglycemia-induced
      endothelial cell proliferation, thus suggesting that the effect might be mediated
      by PAC1 and VPAC2 receptors.

PMID- 20800634
TI  - Selective substitution of amino acids limits proteolytic cleavage and improves
      the bioactivity of an anti-biofilm peptide that targets the periodontal pathogen,
      Porphyromonas gingivalis.
AB  - The interaction of the periodontal pathogen, Porphyromonas gingivalis, with oral
      streptococci such as Streptococcus gordonii precedes colonization of the
      subgingival pocket and represents a target for limiting P. gingivalis
      colonization of the oral cavity. Previous studies showed that a synthetic peptide
      (designated BAR) derived from the antigen I/II protein of S. gordonii was a
      potent competitive inhibitor of P. gingivalis adherence to S. gordonii and
      subsequent biofilm formation. Here we show that despite its inhibitory activity,
      BAR is rapidly degraded by intact P. gingivalis cells in vitro. However, in the
      presence of soluble Mfa protein, the P. gingivalis receptor for BAR, the peptide
      is protected from proteolytic degradation suggesting that the affinity of BAR for
      Mfa is higher than for P. gingivalis proteases. The rate of BAR degradation was
      reduced when the P. gingivalis lysine-specific gingipain was inhibited using the
      specific protease inhibitor, z-FKcK, or when the gene encoding the Lys-gingipain
      was inactivated. In addition, substituting d-Lys for l-Lys residues in BAR
      prevented degradation of the peptide when incubated with the Lys-gingipain and
      increased its specific adherence inhibitory activity in a S. gordonii-P.
      gingivalis dual species biofilm model. These results suggest that Lys-gingipain
      accounts in large part for P. gingivalis-mediated degradation of BAR and that
      more effective peptide inhibitors of P. gingivalis adherence to streptococci can
      be produced by introducing modifications that limit the susceptibility of BAR to
      the Lys-gingipain and other P. gingivalis associated proteases.

PMID- 20800635
TI  - Antihypertensive effect of insect cells: in vitro and in vivo evaluation.
AB  - In this study, we investigated the in vitro ACE inhibitory and in vivo
      antihypertensive effect of insect cell extracts. The IC(50) of three insect cell
      lines from different type and insect species origin: S2 (embryo, Drosophila
      melanogaster), Sf21 (ovary, Spodoptera frugiperda) and Bm5 (ovary, Bombyx mori),
      were evaluated. Most interesting results were that the IC(50) values ranged
      between 0.4 and 0.9 mg/ml, and that an extra hydrolysis with gastrointestinal
      enzymes did not increase the ACE inhibitory activity conspicuously. Finally, a
      single oral administration with a gavage of 150 mg cell extract/kg BW to
      spontaneous hypertensive rats (SHR) significantly decreased (p<0.05) their
      systolic blood pressure (SBP) with 5-6% (9-12 mmHg) compared to the controls at 6
      h post-administration. Here the undigested and digested insect S2 cell extracts
      were equal in activity to lower the SBP. To the best of our knowledge, this is
      the first report of in vivo antihypertensive activity of insect cell extracts and
      this without an extra digestion requirement.

PMID- 20800636
TI  - Effect of MTII on food intake and brain c-Fos in melanocortin-3, melanocortin-4,
      and double MC3 and MC4 receptor knockout mice.
AB  - Mice with genomic knockout of either melanocortin type 3 receptors (MC3R-/-),
      type 4 receptors (MC4R-/-) or knockout of both (double knockout, DKO) were tested
      for their anorectic response to the mixed MC3/4R agonist, MTII, injected into the
      anterior cerebral ventricle. Wild type (WT) mice showed a strong anorexia and, as
      expected, DKO were completely unresponsive to MTII. In contrast, both MC3R-/- and
      MC4R-/- showed a partial anorectic response. Induction of c-Fos immunoreactivity
      by MTII was examined in brain regions including paraventricular hypothalamus
      (PVN) and area postrema (AP). Compared with WT, MC4R-/- showed no activation in
      AP but showed normal activation in PVN, whereas MC3R-/- showed reduced activation
      in PVN but not in AP. RT-PCR analysis showed that hypothalamic mRNA for MC3R in
      MC4R-/- and for MC4R in MC3R-/- was unaltered from WT levels. These data suggest
      that both receptor subtypes are involved in the behavioral action of MTII, and
      that the critical receptors are in different brain regions.

PMID- 20800637
TI  - Central Neuropeptide S inhibits food intake in mice through activation of
      Neuropeptide S receptor.
AB  - Neuropeptide S (NPS), the endogenous ligand of NPS receptor (NPSR), can regulate
      a variety of biological functions, including arousal, anxiety, locomotion, memory
      and drug abuse. Previous studies have shown that central NPS inhibited food
      intake in rats and chicks. In the present study, we investigated the role of
      central NPS on food intake in fasted mice, and detected the underlying
      mechanism(s) by using NPSR antagonist [D-Val(5)]NPS and Corticotropin-Releasing
      Factor 1 (CRF1) Receptor antagonist NBI-27914. The present results indicated that
      intracerebroventricular injection of NPS (0.001-0.1 nmol) dose-dependently
      inhibited food intake in fasted mice. The anorectic effect of NPS reached the
      maximum at the dose of 0.1 nmol, which could be antagonized by co-injection of 10
      nmol NPSR antagonist [D-Val(5)]NPS. Furthermore, CRF1 receptor antagonist NBI
      27914 at the dose of 2 MUg antagonized the hyperlocomotor action of NPS, but did
      not affect the role of NPS on food intake. In conclusion, our results
      demonstrated central NPS inhibited food intake in fasted mice, mediated by its
      cognate NPSR, but not by CRF1 receptor.

PMID- 20800638
TI  - Structure-activity studies of RALF, Rapid Alkalinization Factor, reveal an
      essential--YISY--motif.
AB  - Rapid Alkalinization Factor (RALF) is a 49-amino acid peptide initially isolated
      from tobacco leaves that is capable of arresting both root and pollen tube
      growth. With suspension cells, addition of RALF causes an elevation of the pH of
      the extracellular media, caused by the blockage of a proton pump. RALF associates
      with a putative receptor(s) on the surface of the plant cell, initiating a signal
      transduction pathway. Although the exact function(s) of RALFs are unknown, its
      presence throughout the plant kingdom attests to its importance in some type of
      basic regulatory role. In the present study, deletion and substitution analyses
      of RALF reveal a specific - YISY - motif located at positions 5 through 8 from
      the N-terminus, highly conserved within the plant kingdom, which is a requirement
      for productive binding of RALF to its putative receptor. Replacement of
      isoleucine with alanine in the - YISY - motif caused a severe reduction in
      alkalinization of suspension cell media and a loss of root growth inhibition with
      tomato seedlings.

PMID- 20800639
TI  - Review of fullerene toxicity and exposure--appraisal of a human health risk
      assessment, based on open literature.
AB  - Fullerenes have gained considerable attention due to their anti-oxidant and
      radical scavenging properties. Their current applications include targeted drug
      delivery, energy application, polymer modifications and cosmetic products. The
      production of fullerenes and their use in consumer products is expected to
      increase in future. This study aims to investigate the feasibility and challenges
      associated with conducting a human health risk assessment for fullerenes based on
      the open literature, utilising an approach similar to that of a classical
      regulatory risk assessment. Available data relates to different types of
      fullerenes (with varying size, surface chemistry, solubility,
      aggregation/agglomeration) and care should therefore be taken when drawing
      general conclusions across the parameters. Pristine fullerenes have shown low
      toxicity and there is probably no risks expected for humans exposed to fullerenes
      in the workplace under good hygiene conditions. The main concern for consumers is
      exposure via direct dermal application of fullerenes present in cosmetics.
      Available studies do not indicate a short term risk from the tested fullerene
      types, however no extrapolation to all fullerene types and to chronic exposure
      can be made. In conclusion, the current dataset on fullerenes in relation to
      both, human exposure and hazard is limited and does not allow reaching any
      definite conclusions suitable for regulatory decision making. Main future work
      should focus on generating occupational and consumer exposure data, as well as
      suitable data on toxicokinetics and potential toxic effects following repeated
      inhalation and dermal exposure allowing to determine a NOAEL. It seems also
      relevant to clarify whether certain fullerene types may potentially induce
      genotoxic and/or carcinogenic effects via physiologically relevant routes.

PMID- 20800640
TI  - Association analysis between polymorphisms in the myo-inositol monophosphatase 2
      (IMPA2) gene and bipolar disorder.
AB  - Linkage studies in bipolar disorder (BPD) suggest that a susceptibility locus
      exists on chromosome 18p11. The myo-inositol monophosphatase 2 gene (IMPA2) maps
      to this genomic region. Myo-inositol monophosphatase dephosphorylates inositol
      monophosphate, regenerating free inositol. Lithium, a common treatment for BPD,
      has been shown to inhibit IMPA2 activity and decrease levels of inositol. It is
      hypothesized that lithium conveys its therapeutic effect for BPD patients
      partially through inositol regulation. Hence, dysfunction of inositol caused by
      IMPA2 irregularity may contribute to the pathophysiology of BPD. In this study,
      we hypothesize that genetic variations in the IMPA2 gene contributes to increased
      susceptibility to BPD. We tested this hypothesis by genotyping 9 SNPs (rs1787984;
      rs585247; rs3974759; rs650727; rs589247; rs669838; rs636173; rs3786285; rs613993)
      in BPD patients (n=556) and controls (n=735). Genotype and allele frequencies
      were compared between groups using Chi square contingency analysis. Linkage
      disequilibrium (LD) between markers was calculated and estimated haplotype
      frequencies were compared between groups. Single marker analysis revealed several
      associations between IMPA2 variations and BPD, which were subsequently rendered
      non-significant after correction for multiple testing. Although our study did not
      show strong support for an association between the tested IMPA2 polymorphisms and
      susceptibility to BPD, additional larger studies are necessary to comprehensively
      investigate a role of the IMPA2 gene in the pathophysiology of BPD.

PMID- 20800641
TI  - Association between the dopamine transporter gene and the inattentive subtype of
      attention deficit hyperactivity disorder in Taiwan.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common heritable childhood
      psychiatric disorder. Since methylphenidate, one of the main drugs used to treat
      ADHD, targets the dopamine transporter, this study examined the linkage
      disequilibrium (LD) structure of the dopamine transporter gene (DAT1) and
      investigated whether the DAT1 gene was associated with ADHD. This Chinese family
      based association sample consisted of 273 DSM-IV diagnosed ADHD probands and
      their family members (n=906). We screened 15 polymorphisms across the DAT1 gene,
      including 14 single nucleotide polymorphism (SNP) markers and the variable number
      of tandem repeat (VNTR) polymorphism in 3'-untranslated region (3'UTR).
      Calculations of pairwise LD revealed three main haplotype blocks (HBs): HB1
      (intron 2 through intron 6), HB2 (intron 8 through intron 11), and HB3 (3'UTR).
      Family-Based Association Tests showed that no allele was significantly more
      transmitted than expected to the ADHD children for these 15 markers. Haplotype
      Based Association Tests showed that a haplotype rs27048 (C)/rs429699 (T) was
      significantly associated with the inattentive subtype (P=0.008). In quantitative
      analyses, this haplotype also demonstrated significant association with the
      inattention severity (P=0.012). Our finding of the haplotype rs27048 (C)/rs429699
      (T) as a novel genetic marker in the inattentive ADHD subtype suggests that
      variation in the DAT1 gene may primarily affect the inattentive subtype of ADHD.

PMID- 20800642
TI  - The relationship between baseline prepulse inhibition levels and ethanol
      withdrawal severity in rats.
AB  - Baseline prepulse inhibition (PPI) of the acoustic startle reflex is thought to
      reflect the functioning of the sensorimotor gating system in the brain. The
      current literature indicates that similar neurotransmitter systems may play roles
      both in the regulation of PPI and in the development of ethanol withdrawal
      syndrome (EWS). The aim of the present study was to test if individual baseline
      PPI levels have any relationship to the behavioral and neurochemical consequences
      of EWS in rats. A batch of rats (n=30) was sorted according to baseline PPI
      levels and classified as either high-inhibitory (HI) or low-inhibitory (LI) rats
      (n=10 in each group). Ethanol was administered in a liquid diet for 21 days. On
      the 22nd day, ethanol was removed from the diet, and EWS was induced. At the 2nd,
      4th, and 6th hours of EWS, locomotor activity and behavioral symptoms were
      evaluated. Brain tissue concentrations of dopamine, serotonin and noradrenaline
      in hippocampus, cortex, and striatum were measured after the 6th hour of EWS
      testing. Another batch of rats (n=30) was classified using the same procedure and
      fed with regular diet. On the 22nd day, rats were decapitated and neurochemical
      measurements were repeated. HI and LI rats consumed similar amounts of ethanol.
      However, EWS signs such as stereotyped behaviors, wet-dog shakes, and tremor were
      more intense in LI rats compared to their HI counterparts. Audiogenic seizures
      occurred in both groups in a similar manner. Although the catecholamine
      concentrations in the brains of both groups were parallel under baseline
      conditions, dopamine levels increased in the cortex of LI and in the striatum of
      HI rats, whereas striatum serotonin levels decreased only in LI rats after the
      6th hour of EWS. In conclusion, the data suggest that the behavioral symptoms and
      neurochemical changes observed in EWS may be associated with baseline PPI levels.

PMID- 20800643
TI  - Exposure to the context and removing the unpredictability of the US: two methods
      to reduce contextual anxiety compared.
AB  - Chronic anxiety may differ from cued fear and hence require other treatment
      strategies. In a human fear conditioning paradigm, chronic anxiety to the
      experimental context was experimentally induced by presenting unpredictable
      shocks. Two methods to reduce chronic anxiety were tested and compared. First, in
      parallel with the standard extinction procedure, participants were exposed to the
      anxiety-eliciting context in the absence of shocks (context-exposure group).
      Second, an alternative procedure was tested in which the previously unpredictable
      shocks were now signaled by a specific cue (signaled group). A control group
      continued to receive unsignaled shocks. Results indicated that chronic contextual
      anxiety, as measured by fear-potentiated startle and US-expectancy ratings, was
      equally reduced in the context-exposure group as in the signaled group compared
      with the control group. When applied to the treatment of, for example, panic
      disorder, these findings support the idea that exposure to the context in which
      the unpredictable panic attacks occurred and making unpredictable panic attacks
      predictable, are both valuable methods in order to reduce chronic anxiety.

PMID- 20800645
TI  - Acquisition of G0 state by CD34-positive cord blood cells after bone marrow
      transplantation.
AB  - OBJECTIVE: Hematopoietic stem cells are kept in a quiescent state in the hypoxic
      area of the bone marrow, which is essential for hematopoietic stem cell
      maintenance. However, when and how hematopoietic stem cells acquire their hypoxic
      state and maintain quiescence has not been fully elucidated. The aim of this
      study was to understand this process in human hematopoietic stem cells after bone
      marrow transplantation. MATERIALS AND METHODS: Human CD34-positive cord blood
      cells were transplanted into nonobese diabetic/severe combined immunodeficient
      interleukin-2 receptor gamma chain knockout mice. Cell cycle and hypoxia assay
      analyses were performed, to identify changes in the characteristics of human
      hematopoietic stem cells following transplantation. Quantitative real-time
      reverse transcription polymerase chain reaction analysis was used to analyze the
      transcriptional changes accompanying this transition. RESULTS: Engrafted
      primitive lineage-negative CD34-positive CD38-negative cells acquired hypoxic
      state and quiescence in the recipient bone marrow between 4 and 8 weeks, and
      between 8 and 12 weeks after transplantation, respectively. During 4 and 8 weeks
      after transplantation, changes in the transcription levels of G0 regulatory
      factors, such as CCNC and RBL1, and stem cell regulators, such as Flt3, were also
      seen, which may be related to the characteristic changes in the cell cycle or
      oxygenation state. CONCLUSIONS: Behavioral changes of hematopoietic stem cells in
      their cell cycle and oxygenation state during and after bone marrow engraftment
      may provide insights into hematopoietic stem cell regulation, mediating the
      improvement of clinical hematopoietic stem cell transplantation protocols and the
      eradication of leukemia stem cells.

PMID- 20800644
TI  - Evidence of mobilization of pluripotent stem cells into peripheral blood of
      patients with myocardial ischemia.
AB  - OBJECTIVE: The ischemic myocardium releases multiple chemotactic factors
      responsible for the mobilization and recruitment of bone marrow-derived cells to
      injured myocardium. However, the mobilization of primitive pluripotent stem cells
      (PSCs) enriched in very small embryonic-like stem cells (VSELs) in various
      cardiac ischemic scenarios is not well understood. MATERIALS AND METHODS: Fifty
      four ischemic heart disease patients, including subjects with stable angina, non
      ST elevation myocardial infarction, and ST elevation myocardial infarction
      (STEMI) and 12 matched controls were enrolled. The absolute numbers of
      circulating stem/primitive cells in samples of peripheral blood (PB) were
      quantitated by ImageStream analysis and conventional flow cytometry. Gene
      expression of PSC (Oct-4 and Nanog), early cardiomyocyte (Nkx-2.5 and GATA-4),
      and endothelial (von Willebrand factor) markers was analyzed by real-time
      polymerase chain reaction. RESULTS: The absolute numbers of PSCs, stem cell
      populations enriched in VSELs, and hematopoietic stem cells present in PB were
      significantly higher in STEMI patients at presentation and declined over time.
      There was a corresponding increase in pluripotent, cardiac, and endothelial gene
      expression in unfractionated PB cells and sorted PB-derived primitive CD34(+)
      cells. The absolute numbers of circulating VSELs and hematopoietic stem cells in
      STEMI correlated negatively with patient age. CONCLUSIONS: Myocardial ischemia
      mobilizes primitive PSCs including pluripotent VSELs into the circulation. The
      peak of mobilization occurs within 12 hours in patients presenting with STEMI,
      which may represent a therapeutic window for future clinical applications.
      Reduced stem cell mobilization with advancing age could explain, in part, the
      observation that age is associated with poor prognosis in patients with
      myocardial infarction.

PMID- 20800646
TI  - Effects of anesthetic propofol on release of amino acids from the spinal cord
      during visceral pain.
AB  - As one of general anesthetics, propofol, has been used for surgical procedures of
      visceral organs. However, the mechanisms underlying the action of propofol on
      visceral nociception remain controversial. The aim of this study is to test
      whether the antinociception of systemic administration of propofol against
      visceral stimuli is related to the changes in release of excitatory and
      inhibitory amino acids in the spinal cord. The spinal microdialysis catheters
      were implanted subarachnoidally via the atlanto-occipital membrane in healthy SD
      rats. The rats received an intraperitoneal injection of acetic acid for visceral
      pain induction 10min after intraperitoneal pretreatment with vehicle or propofol
      (100mg/kg). The acetic acid-induced writhing assay was used to determine the
      degree of antinociception. Cerebrospinal fluid dialysate was collected by
      microdialysis from the spinal subarachnoid space before pretreatment and after
      visceral pain induction. Visceral pain-induced release of amino acids into the
      dialysate, including glutamate, aspartate, and gamma-amino butyric acid was
      evaluated by measuring the changes in the concentrations of these amino acids.
      Acetic acid increased release of aspartate and glutamate, and decreased release
      of gamma-amino butyric acid in the cerebrospinal fluid as measured by
      microdialysis. Pretreatment with propofol significantly decreased writhing
      responses induced by visceral pain, suppressed the visceral pain-induced
      aspartate and glutamate release, and reversed the decreased release of gamma
      amino butyric acid in the cerebrospinal fluid. These data provide evidence for a
      potential mechanism for the antinociceptive effects of propofol on visceral
      nociception.

PMID- 20800647
TI  - Injury-induced CRMP4 expression in adult sensory neurons; a possible target gene
      for ciliary neurotrophic factor.
AB  - Neurotrophic cytokines, such as ciliary neurotrophic factor (CNTF) play an
      important role in the development and regeneration of the nervous system. In the
      present study, we screened gene expression induced by CNTF in adult dorsal root
      ganglion (DRG) neurons using the Illumina microarray. We found that the
      expression of both short and long forms of collapsin response-mediator protein 4
      (CRMP4) was increased in cultured primary sensory neurons by CNTF. In addition,
      sciatic nerve injury induced the expression of CRMP4 mRNA and protein in DRG
      neurons. Finally, the increased CRMP4 protein was transported into peripheral
      axons following nerve injury. These findings indicate that CRMP4 may be a target
      gene for CNTF in the regenerative axon growth of DRG neurons after injury.

PMID- 20800648
TI  - Effects of C3 deficiency on inflammation and regeneration following spinal cord
      injury in mice.
AB  - Inflammation can activate the complement system, which in turn enhances
      inflammation and aggravates secondary injury after spinal cord injury (SCI). As
      the three complement activation pathways converge at the cleavage of C3, we
      investigated whether inhibiting complement activation in C3-deficient mice would
      reduce secondary injury after SCI and improve axon regeneration. Weight-drop
      contusion injury (5g, 6cm) was created in wild-type or C3-deficient mice.
      Astrocytes (ASTs) activation, TNF-alpha expression, and axon regeneration were
      investigated in vivo. In other studies, dorsal root ganglia (DRGs) were co
      cultured with mechanically injured ASTs in vitro to evaluate effects on neurite
      outgrowth. Our results show that, after injury, C3-deficient mice exhibit higher
      BBB scores than wild-type mice. In addition, ASTs activation was inhibited, TNF
      alpha expression process was delayed in vivo and inhibited in vitro, and nerve
      fiber regeneration was improved in C3-deficient mice. DRGs co-cultured with
      mechanically injured ASTs from C3-deficient mice also showed improved neurite
      outgrowth. We conclude that C3 deficiency can inhibit inflammation through
      suppressing ASTs activation and TNF-alpha expression, thereby reducing secondary
      injury and improving neural regeneration and functional recovery after SCI. The
      above results suggest that complement inhibition may be a potential therapy to
      promote central nervous system regeneration by targeting C3.

PMID- 20800649
TI  - Brain resting state is disrupted in chronic back pain patients.
AB  - Recent brain functional magnetic resonance imaging (fMRI) studies have shown that
      chronic back pain (CBP) alters brain dynamics beyond the feeling of pain. In
      particular, the response of the brain default mode network (DMN) during an
      attention task was found abnormal. In the present work similar alterations are
      demonstrated for spontaneous resting patterns of fMRI brain activity over a
      population of CBP patients (n=12, 29-67 years old, mean=51.2). Results show
      abnormal correlations of three out of four highly connected sites of the DMN with
      bilateral insular cortex and regions in the middle frontal gyrus (p<0.05), in
      comparison with a control group of healthy subjects (n=20, 21-60 years old,
      mean=38.4). The alterations were confirmed by the calculation of triggered
      averages, which demonstrated increased coactivation of the DMN and the former
      regions. These findings demonstrate that CBP disrupts normal activity in the DMN
      even during the brain resting state, highlighting the impact of enduring pain
      over brain structure and function.

PMID- 20800650
TI  - Overexpression of CD133 promotes the phosphorylation of Erk in U87MG human
      glioblastoma cells.
AB  - An increasing number of studies support the presence of stem-like cells in human
      malignancies. These cells are primarily responsible for tumor initiation and thus
      considered as a potential target to eradicate tumors. CD133 has been identified
      as an important cell surface marker to enrich the stem-like population in various
      human tumors. However, the biological function of CD133 protein remains unknown.
      In this study, we observed no significant effects on cell proliferation and
      migration in CD133 overexpressed U87MG human glioblastoma cells. It is reported
      that MAPK/Erk was constitutively activated in CD133 positive liver cancer stem
      cell. To find out possible mechanism between CD133 and Erk phosphorylation, we
      performed this study to evaluate the level of Erk phosphorylation in CD133
      overexpressed U87MG cells. We found that CD133 overexpression significantly
      activated Erk, which suggested CD133 involved in activation of MAPK/Erk pathway.

PMID- 20800651
TI  - Serum anti-inflammatory markers in general population subjects with elevated
      depressive symptoms.
AB  - Anti-inflammatory substances have previously been suggested to show compensatory
      elevations in depressed individuals with pronounced inflammatory changes. In
      order to further clarify these observations, we examined depression-related
      alterations in the serum levels of anti-inflammatory markers interleukin (IL)-1
      receptor antagonist (RA) and IL-10 and the pro-inflammatory marker IL-6 in 416
      general population participants. Depression was evaluated with the Beck
      Depression Inventory (BDI). Participants with elevated depressive symptoms
      (BDI>14, n=44) had increased levels of IL-1 RA and IL-6. No changes were observed
      in their IL-10 levels. In multivariate modeling with adjustments for age, gender,
      obesity, regular smoking, alcohol use, metabolic syndrome, physical exercise,
      sleep disturbance, and the use of non-steroidal anti-inflammatory drugs, a high
      level of IL-1 RA was associated with an increased likelihood of belonging to the
      group with elevated depressive symptoms (OR for each 1 SD increase in the serum
      level of IL-1 RA: 2.17, 95% CI 1.35-3.48, p=0.001). The significance of IL-6
      alterations did not persist in the same model. The pronounced secretion of anti
      inflammatory marker IL-1 RA may reflect the presence of compensatory mechanisms
      during a depression-related inflammatory state.

PMID- 20800652
TI  - Why do we need another interferon?

PMID- 20800654
TI  - Trouble with a shunt: alcohol and spastic paraparesis. Hepatic myelopathy.

PMID- 20800653
TI  - Acute obstructive cholangitis due to foreign body in the common bile duct.
      Migrated endoclip.

PMID- 20800655
TI  - Epithelial to mesenchymal transition in injury of solid organs: fact or artifact?

PMID- 20800656
TI  - A pancreatic mass presented with multiple hot spots in the subcutaneous fat layer
      on positron emission tomography. Acinar cell carcinoma with multiple fat
      necrosis.

PMID- 20800657
TI  - Colonic polyposis: more than meets the eye. Metastatic melanoma.

PMID- 20800658
TI  - Anandamide centrally depresses the respiratory rhythm generator of neonatal mice.
AB  - Endogenous cannabinoid receptors are widely distributed throughout the CNS,
      including the brainstem, and modulate a variety of functions, including
      breathing. In adult rats, activation of cannabinoid 1 receptors has been shown to
      depress breathing. Here in neonatal mice, we used in vitro electrophysiology,
      pharmacology, and immunohistochemistry to analyse the central effects of the
      endocannabinoid anandamide (AEA) on the activity of the medullary respiratory
      rhythm generator (RRG). First of all, in vitro electrophysiology on medullary
      preparations has revealed that bath application of AEA (30 MUM, 15 min)
      significantly depressed respiratory activity. Secondly, applying pre-treatments
      with alpha-1 (Prazosin, 5 MUM, 10 min) and alpha-2 (Yohimbine, 5 MUM, 10 min)
      adrenoceptor antagonists prior to AEA application abolished the AEA-induced
      depression of the RRG. Finally, immunostaining revealed a dense network of fibres
      positive for the cannabinoid 1 receptor in the ventrolateral medulla (VLM), a
      region known to contain both the RRG and the modulatory A1/C1 catecholaminergic
      group. Moreover, cannabinoid 1 receptor positive fibres were found in close
      apposition with A1/C1 catecholaminergic cells, identified by the presence of
      tyrosine hydroxylase. In regard of our electrophysiological, pharmacological and
      immunostaining results, we conclude that AEA has a central depressive effect on
      the neonatal RRG, probably via the medullary A1/C1 catecholaminergic neurons
      which are already known to modulate the respiratory rhythm generator.

PMID- 20800659
TI  - Peripheral nerve injury differentially regulates dopaminergic pathways in the
      nucleus accumbens of rats with either 'pain alone' or 'pain and disability'.
AB  - Following unilateral chronic constriction injury (CCI) of the sciatic nerve,
      histochemical and gene expression changes were examined in the rat nucleus
      accumbens (NAcc), a region critical to affective-motivational regulation. Rats
      were categorised as having Pain alone (45%) or Pain and Disability (30%), on the
      basis of either unaltered or decreased dominance behaviour in the resident
      intruder paradigm, respectively. Tyrosine hydroxylase (TH) expression was
      significantly increased bilaterally, throughout the rostrocaudal extent of the
      NAcc in Pain alone animals. Increased TH likely reflects increased dopamine
      levels in the Pain alone group, which may modulate dopamine receptor subtype 2
      (D2) receptor expression. Stereological analyses of D2 receptor immunoreactive
      (D2-IR) cells revealed lateralised changes which correlated significantly with
      dominance behaviour. In the contralateral NAcc, D2-IR negatively correlated with
      post-CCI dominance behaviour (i.e. Pain alone animals have decreased D2-IR),
      whereas ipsilaterally there was a positive correlation between D2-IR and post-CCI
      dominance behaviour (i.e. Pain and Disability animals have decreased D2-IR).
      Western blots for D2 protein expression confirmed these correlations.
      Additionally, D2 mRNA expression within the NAcc showed lateralised and group
      specific changes. In the ipsilateral NAcc D2 mRNA was increased in Pain alone
      animals. It is hypothesised that increased D2 mRNA in the ipsilateral NAcc of
      Pain alone animals may be a protective mechanism, maintaining D2-IR despite
      increased dopamine, which may otherwise induce receptor desensitisation. D2 mRNA
      is not altered in the ipsilateral NAcc of Pain and Disability animals, therefore
      loss of D2-IR is likely, albeit by an alternate mechanism. In summary, unilateral
      CCI in rats induces specific and lateralised adaptations in the dopaminergic
      circuitry of the NAcc. These distinct neural adaptations correlate with changes
      in social behaviour, and likely underlie some of the affective-motivational state
      changes associated with neuropathic pain in a subset of rats (i.e. Pain and
      Disability group).

PMID- 20800660
TI  - Minimum neuron density for synchronized bursts in a rat cortical culture on multi
      electrode arrays.
AB  - To investigate the minimum neuron and neurite densities required for synchronized
      bursts, we cultured rat cortical neurons on planar multi-electrode arrays (MEAs)
      at five plating densities (2500, 1000, 500, 250, and 100 cells/mm(2)) using two
      culture media: Neuron Culture Medium and Dulbecco's Modified Eagle Medium
      supplemented with serum (DMEM/serum). Long-term recording of spontaneous
      electrical activity clarified that the cultures exhibiting synchronized bursts
      required an initial plating density of at least 250 cells/mm(2) for Neuron
      Culture Medium and 500 cells/mm(2) for DMEM/serum. Immediately after electrical
      recording, immunocytochemistry of microtubule-associated protein 2 (MAP2) and
      Neurofilament 200 kD (NF200) was performed directly on MEAs to investigate the
      actual densities of neurons and neurites forming the networks. Immunofluorescence
      observation revealed that the construction of complicated neuronal networks
      required the same initial plating density as for synchronized bursts, and that
      overly sparse cultures showed significant decreases of neurons and neurites. We
      also found that the final densities of surviving neurons at 1 month decreased
      greatly compared with the initial plating densities and became saturated in
      denser cultures. In addition, the area of neurites and the number of nuclei were
      saturated in denser cultures. By comparing both the results of
      electrophysiological recording and immunocytochemical observation, we revealed
      that there is a minimum threshold of neuron densities that must be met for the
      exhibition of synchronized bursts. Interestingly, these minimum densities of MAP2
      positive final neurons did not differ between the two culture media; the density
      was approximately 50 neurons/mm(2). This value was obtained in the cultures with
      the initial plating densities of 250 cells/mm(2) for Neuron Culture Medium and
      500 cells/mm(2) for DMEM/serum.

PMID- 20800661
TI  - Proline-rich synapse-associated protein-1 and 2 (ProSAP1/Shank2 and
      ProSAP2/Shank3)-scaffolding proteins are also present in postsynaptic
      specializations of the peripheral nervous system.
AB  - Proline-rich synapse-associated protein-1 and 2 (ProSAP1/Shank2 and
      ProSAP2/Shank3) were originally found as synapse-associated protein
      90/postsynaptic density protein-95-associated protein (SAPAP)/guanylate-kinase
      associated protein (GKAP) interaction partners and also isolated from synaptic
      junctional protein preparations of rat brain. They are essential components of
      the postsynaptic density (PSD) and are specifically targeted to excitatory
      asymmetric type 1 synapses. Functionally, the members of the ProSAP/Shank family
      are one of the postsynaptic key elements since they link and attach the
      postsynaptic signaling apparatus, for example N-methyl-d-aspartic acid (NMDA)
      receptors via direct and indirect protein interactions to the actin-based
      cytoskeleton. The functional significance of ProSAP1/2 for synaptic transmission
      and the paucity of data with respect to the molecular composition of PSDs of the
      peripheral nervous system (PNS) stimulated us to investigate neuromuscular
      junctions (NMJs), synapses of the superior cervical ganglion (SCG), and synapses
      in myenteric ganglia as representative synaptic junctions of the PNS. Confocal
      imaging revealed ProSAP1/2-immunoreactivity (-iry) in NMJs of rat and mouse
      sternomastoid and tibialis anterior muscles. In contrast, ProSAP1/2-iry was only
      negligibly found in motor endplates of striated esophageal muscle probably caused
      by antigen masking or a different postsynaptic molecular anatomy at these
      synapses. ProSAP1/2-iry was furthermore detected in cell bodies and dendrites of
      superior cervical ganglion neurons and myenteric neurons in esophagus and
      stomach. Ultrastructural analysis of ProSAP1/2 expression in myenteric ganglia
      demonstrated that ProSAP1 and ProSAP2 antibodies specifically labelled PSDs of
      myenteric neurons. Thus, scaffolding proteins ProSAP1/2 were found within the
      postsynaptic specializations of synapses within the PNS, indicating a similar
      molecular assembly of central and peripheral postsynapses.

PMID- 20800662
TI  - The effect of Delta9-tetrahydrocannabinol on 5-HT3 receptors depends on the
      current density.
AB  - The effects of Delta(9)-tetrahydrocannabinol (THC), the psychoactive component of
      cannabis, on the function of 5-HT type 3 (5-HT(3)) receptors were investigated
      using a two-electrode voltage clamp technique in Xenopus oocytes, and a whole
      cell patch clamp technique in rat nodose ganglion neurons. In oocytes injected
      with 3 ng cRNA of 5-HT(3A) receptor, THC reversibly inhibited currents evoked
      with 5-HT (1 MUM) in a concentration-dependent manner (IC(50)=1.2 MUM). The
      extent of THC inhibition was inversely correlated with the amount of cRNA
      injected and the mean 5-HT(3A) receptor current densities. Pretreatment with
      actinomycin D, which inhibits transcription, decreased the mean 5-HT(3) receptor
      current density and increased the extent of THC inhibition on 5-HT(3) receptor
      mediated currents. The IC(50) values for THC increased from 285 nM to 1.2 MUM in
      oocytes injected with 1 and 3 ng of 5-HT(3A) cRNA, respectively. In radioligand
      binding studies on membrane preparations of oocytes expressing 5-HT(3A)
      receptors, THC did not alter the specific binding of a 5-HT(3A) receptor
      antagonist, [(3)H]GR65630. In the presence of 1 MUM THC, the maximum 5-HT-induced
      response was also inhibited without a significant change in 5-HT potency,
      indicating that THC acts as a noncompetitive antagonist on 5-HT(3) receptors. In
      adult rat nodose ganglion neurons, application of 1 MUM THC caused a significant
      inhibition of 5-HT(3) receptors, extent of which correlated with the density of 5
      HT-induced currents, indicating that the observed THC effects occur in mammalian
      neurons. The inhibition of 5-HT(3) receptors by THC may contribute to its
      pharmacological actions in nociception and emesis.

PMID- 20800663
TI  - Shifting the balance: evidence of an exploratory role for postural sway.
AB  - Humans and other species are unable to stand perfectly still; their bodies
      continuously sway during stance even during concentrated efforts to avoid such
      movement. Traditionally, this phenomenon has been viewed as an inability of the
      central nervous system (CNS) to maintain perfect equilibrium because of its
      reliance on feedback from sensory signals to control corrective ground-reaction
      forces. Using a novel method to minimize movements of the body during stance
      without subject awareness, we have made the unique discovery that ground-reaction
      forces are generated independent of body sway, as evidenced by observations of
      increased centre of pressure variability when postural sway is minimized
      experimentally. Contrary to traditional views, our results suggest that postural
      sway may be used by the CNS as an exploratory mechanism to ensure that continuous
      dynamic inputs are provided by multiple sensory systems. This novel paradigm has
      the potential to significantly shift long-standing views on balance, and
      questions the theoretical basis behind conventional treatment strategies for
      balance deficits associated with age and disease.

PMID- 20800664
TI  - Mesenchymal stem cells in a polycaprolactone conduit enhance median-nerve
      regeneration, prevent decrease of creatine phosphokinase levels in muscle, and
      improve functional recovery in mice.
AB  - Although the majority of peripheral-nerve regeneration studies are carried out on
      the sciatic nerve, lesions of the upper extremities are more common in humans and
      usually lead to significant physical disabilities. The present study was driven
      by the hypothesis that a combination of strategies, namely grafts of mesenchymal
      stem cells (MSC) and resorbable polycaprolactone (PCL) conduits would improve
      median-nerve regeneration after transection. Mouse median nerves were transected
      and sutured to PCL tubes that were filled with either green fluorescent protein
      (GFP(+)) MSC in DMEM or with DMEM alone. During the post-operative period,
      animals were tested weekly for flexor digitorum muscle function by means of the
      grasping test. After 8 weeks, the proximal and middle portions of the PCL tube
      and the regenerating nerves were harvested and processed for light and electron
      microscopy. The flexor digitorum muscle was weighed and subjected to biochemical
      analysis for creatine phosphokinase (CK) levels. Scanning electron microscopy of
      the PCL tube 8 weeks after implantation showed clear signs of wall
      disintegration. MSC-treated animals showed significantly larger numbers of
      myelinated and unmyelinated nerve fibers and blood vessels compared with DMEM
      treated animals. The flexor digitorum muscle CK levels were significantly higher
      in the MSC-treated animals, but muscle weight values did not differ between the
      groups. Compared with the DMEM-treated group, MSC-treated animals showed, by the
      grasping test, improved functional performance throughout the period analyzed.
      Immunofluorescence for S-100 and GFP showed, in a few cases, double-labeled
      cells, suggesting that transplanted cells may occasionally transdifferentiate
      into Schwann cells. Our data demonstrate that the polycaprolactone conduit filled
      with MSC is capable of significantly improving the median-nerve regeneration
      after a traumatic lesion.

PMID- 20800665
TI  - Effect of modafinil on learning performance and neocortical long-term
      potentiation in rats.
AB  - Modafinil is a novel wake-promoting agent whose effects on cognitive performance
      have begun to be addressed at both preclinical and clinical level. The present
      study was designed to investigate in rats the effects of chronic modafinil
      administration on cognitive performance by evaluating: (i) working and reference
      memories in an Olton 4*4 maze, and (ii) learning of a complex operant
      conditioning task in a Skinner box. In addition, the effect of modafinil on the
      ability of the rat frontal cortex to develop long-term potentiation (LTP) was
      also studied. Chronic modafinil did not significantly modify working memory
      errors but decreased long-term memory errors on the Olton 4*4 maze, meaning that
      the drug may have a favourable profile on performance of visuo-spatial tasks
      (typically, a hippocampus-dependent task) when chronically administered. On the
      other hand, chronic modafinil resulted in a marked decrease of successful
      responses in a complex operant conditioning learning, which means that repeated
      administration of the drug influences negatively problem-solving abilities when
      confronting the rat to a sequencing task (typically, a prefrontal cortex
      dependent task). In addition, in vivo electrophysiology showed that modafinil
      resulted in impaired capacity of the rat prefrontal cortex to develop LTP
      following tetanization. It is concluded that modafinil can improve the
      performance of spatial tasks that depend almost exclusively on hippocampal
      functioning, but not the performance in tasks including a temporal factor where
      the prefrontal cortex plays an important role. The fact that modafinil together
      with preventing operant conditioning learning was also able to block LTP
      induction in the prefrontal cortex, suggests that the drug could interfere some
      critical component required for LTP can be developed, thereby altering
      neuroplastic capabilities of the prefrontal cortex.

PMID- 20800666
TI  - Glucose exacerbates zinc-induced astrocyte death.
AB  - Zinc and cytosolic phospholipase A(2) (cPLA(2)) have been implicated in the death
      of neural cells and the pathogenesis of ischemia, and hyperglycemia is a
      potential augmenting factor. However, their potential crosstalk and/or
      interaction in mediating cell damage have not yet been fully elucidated. Here, we
      report that a potential link between cPLA(2) activation and zinc-induced
      astrocyte damage involving reactive oxygen species (ROS)/protein kinase C-alpha
      (PKC-alpha)/extracellular signal-regulated kinase (ERK) signaling and glucose is
      able to increase zinc uptake and potentiate zinc-induced alterations and
      astrocyte damage. The cell death caused by ZnCl(2) was accompanied by increased
      ROS generation, PKC-alpha membrane translocation, ERK phosphorylation, and
      cPLA(2) phosphorylation and activity. Pharmacological studies revealed that these
      activations contributed to ZnCl(2)-induced astrocyte death. Mechanistic studies
      had suggested that ROS/PKC-alpha/ERK was a potential signal linking zinc and
      cPLA(2). Glucose increased zinc uptake and potentiated ZnCl(2)-induced
      alterations and astrocyte death. These observations indicated that ROS/PKC
      alpha/ERK signaling and cPLA(2) were actively involved in zinc-induced astrocyte
      damage, and suggested zinc was a potential downstream effector in hyperglycemia
      aggravated astrocyte injury.

PMID- 20800667
TI  - PYDDT, a novel phase 2 enzymes inducer, activates Keap1-Nrf2 pathway via
      depleting the cellular level of glutathione.
AB  - Keap1-Nrf2 pathway has emerged as a regulator for the endogenous antioxidant
      response, which is critical in defending cells against carcinogenesis. Herein, we
      demonstrated that depleting the cellular level of glutathione (GSH) by a novel
      electrophilic agent 2-(pro-1-ynyl)-5-(5,6-dihydroxypenta-1,3-diynyl) thiophene
      (PYDDT) could activate Keap1-Nrf2 pathway. In above process, it was found that
      Keap1 was modified by S-glutathionylation, an important post-translational
      modification of protein cysteines with critical roles in oxidative stress and
      signal transduction. We concluded from our findings that conjugation with
      intracellular GSH by PYDDT might lead to Keap1 S-glutathionylation and was a key
      event involved in its Nrf2 inducing activity.

PMID- 20800668
TI  - Comparative effects of Rauwolfia vomitoria and chlorpromazine on locomotor
      behaviour and anxiety in mice.
AB  - AIM OF THE STUDY: Since remedies for mental disorders have been sought through
      both orthodox and traditional medicine this study compared the effects of the
      antipsychotic, chlorpromazine (Cpz), the herb Rauwolfia vomitoria (RV) and its
      alkaloid reserpine (Res) in mice. MATERIALS AND METHODS: Ninety male CD-1 strain
      of mice (75-80 days old; 30-34 g body weight) were divided into 3 major groups
      and each consisting 5 subgroups (n=6). Cpz (0.0, 0.25, 1.0, 2.0 and 4.0 mg/kg,
      i.p.), was administered 30 min before testing. RV (0.0, 0.25, 1.0, 2.0 and 4.0
      mg/kg, i.p.) and Res (0.0, 0.1, 0.4, 0.8, 1.6 mg/kg, i.p.) were administered 24 h
      before testing. The open field test was used to assess locomotor and exploratory
      behaviour, acceleratory rotarod for motor coordination, light/dark box for
      anxiety. RESULTS: CPZ dose-dependently decreased locomotor and exploration
      behaviour and impaired motor coordination (p<0.01). RV also decreased locomotor
      behaviour at 4.0 mg/kg (p<0.5) but did not alter exploration and motor
      coordination. Res however, decreased locomotion and exploration and impaired
      motor coordination 0.8 and 1.6 mg/kg (p<0.05). In the light/dark box, CPZ
      increased anxiety related behaviour at 1.0, 2.0 mg/kg (p<0.05) whereas RV dose
      dependently decreased anxiety from 1.0 to 4.0 mg/kg (p<0.01). Res, unlike RV,
      dose-dependently increased anxiety related behaviour from 0.4 to 1.6 mg/kg.
      CONCLUSION: Root bark extract from Rauwolfia vomitoria produced better
      behavioural effects with less distortion in motor coordination when compared to
      chlorpromazine and so has a great potential as an alternative antipsychotic agent
      compared to chlorpromazine. Since Res did not produce same effects as RV, the
      effect of RV may not be due solely to Res as claimed.

PMID- 20800669
TI  - Xanthine oxidase inhibitory properties of Czech medicinal plants.
AB  - AIM OF THE STUDY: To investigate in vitro xanthine oxidase inhibitory properties
      of plants traditionally used in Czech Republic and Central-East Europe region for
      gout, arthritis or rheumatism treatment. MATERIALS AND METHODS: Methylene
      chloride-methanolic and two ethanolic extracts of 27 plant species were screened
      for in vitro xanthine oxidase inhibitory activity using a spectrophotometric
      method. RESULTS: Around 50% of the species exhibited some degree of xanthine
      oxidase inhibitory properties at 200 MUg/mL, showing a moderate correlation
      (r=0.59) with total phenol content. The most active were methylene chloride
      methanolic extracts of Populus nigra and Betula pendula, with IC(50) of 8.3 and
      25.9 MUg/mL, respectively, followed by 80% ethanolic extract of Caryophyllus
      aromaticus and Hypericum perforatum, both under 50 MUg/mL. CONCLUSIONS: Populus
      nigra and Betula pendula were identified as species with the highest xanthine
      oxidase inhibitory potential in our study. This correlates with the
      ethnobotanical data on their use in Central European folklore and provides the
      basis for further investigation on these plants.

PMID- 20800670
TI  - Anti-inflammatory effect of a methanolic extract of leaves of Dregea volubilis.
AB  - AIM OF STUDY: The aim of this study was to establish the anti-inflammatory
      activity of the methanolic extract of Dregea volubilis leaves (MEDV) with its
      fractions and to delineate the possible mechanism of action for MEDV. MATERIALS
      AND METHODS: The anti-inflammatory activities of MEDV along with its petroleum
      ether and chloroform fractions were evaluated in a carrageenan induced model of
      acute inflammation. The effect of MEDV on lipopolysaccharide induced production
      of nitric oxide (NO) in macrophages was also studied. RESULTS: MEDV (100, 200 and
      400 mg/kg body weight) significantly reduced carrageenan induced paw edema;
      chloroform fraction was most potent (66%, p<0.001). MEDV was non-toxic up to 125
      MUg/ml in mouse peritoneal macrophages wherein it (0-100 MUg/ml) reduced
      lipopolysaccharide induced NO production. CONCLUSION: MEDV possesses significant
      anti-inflammatory activity. Chloroform fraction of MEDV showed best anti
      inflammatory activity.

PMID- 20800671
TI  - Acute and sub-chronic toxicity of a lyophilised aqueous extract of Centaurium
      erythraea in rodents.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: An aqueous concoction made from centaury
      (Centaurium erythraea (L.) Rafn., (Gentianaceae) whole plant is used in the
      Moroccan traditional medicine for the treatment of diabetes, as well as a number
      of other diseases. No systematic study of the potential toxicity of the plant has
      been described. AIM OF THE STUDY: The present investigation was carried out to
      evaluate the safety of an aqueous extract of Centaurium erythraea whole plant (CE
      extract) by determining its potential toxicity after acute and sub-chronic
      administration in rats and mice. MATERIALS AND METHODS: For the acute study, the
      lyophilised CE-extract was administered to adult IOPS OFA mice in single oral
      doses of 1-15 g/kg given by gavage, and single intraperitoneal (i.p.) doses of 1
      14 g/kg. General behavioral adverse effects, mortality, and latency of mortality
      were determined for up to 14 days. In the sub-chronic dose study, the CE-extract
      was administered orally at doses of 100, 600 and 1200 mg/kg daily for 90 days to
      Wistar rats. Body weight and selected biochemical and hematological parameters
      were determined every 30 days and at the end of 90 days of daily administration;
      sections of liver and kidney were examined histologically for any signs of organ
      damage at the end of the treatment. RESULTS: In the acute study in mice, there
      were no deaths or any signs of toxicity observed after oral administration of
      single doses of the CE-extract at any dose level up to the highest dose tested
      (15 g/kg), which was the no-observed-adverse-effect level (NOAEL). However, the
      mortality rate as well as the acute toxicity of the i.p. administered CE-extract
      increased progressively with increasing dose. The NOAEL for the i.p. dose was 6
      g/kg while the lowest-observed-adverse-effect level (LOAEL) was 8 g/kg; the
      calculated acute toxicity (LD(50)) of i.p. administered CE-extract in mice was
      12.13 g/kg. In sub-chronic studies in rats, the CE-extract (administered orally
      at daily doses of 100, 600 and 1200 mg/kg for 90 days), did not cause any changes
      in hematological and biochemical parameters, except a small reduction of mean
      corpuscular volume, and a decrease in serum glucose and triglyceride levels at
      the higher doses. Histopathological examination of the liver and kidneys at the
      end of the study showed normal architecture suggesting no morphological
      disturbances. CONCLUSIONS: Because of the lack of toxicity of the CE-extract
      given by the oral route, and relatively high NOAEL values for the i.p. dose in
      the acute study in mice, as well as lack of mortality or clinically significant
      adverse changes in the biological and hematological parameters, and the
      morphology of liver and kidneys in rats after 90 days of daily dosing, it may be
      concluded that the CE-extract is relatively non-toxic. Also, in view of the doses
      consumed empirically in traditional medicine in Morocco, there is a wide margin
      of safety for the therapeutic use of Centaurium erythraea.

PMID- 20800672
TI  - Drosophila as a model for age-related impairment in locomotor and other
      behaviors.
AB  - Aging is a multifaceted phenomenon that occurs in most species including humans
      and the fruit fly, Drosophila melanogaster. One of the most fundamental features
      of aging is the progressive decline in functional capacity that occurs with age
      (i.e. functional senescence). Age-related declines in function undermine many
      aspects of normal youthful physiology including behavior. Age-related behavioral
      declines are quite telling because they presumably reflect primary functional
      defects in the nervous system or musculature. Consequently, a more detailed
      understanding of behavioral declines that occur with age, including mechanisms
      that impinge on them, could ultimately lead to improved treatment or diagnosis of
      age-related defects in physiological processes that depend on normal function of
      the nervous system or musculature. Such advances in diagnosis or treatment would
      translate into tremendous gains in quality of life for elderly populations. In
      this article, we review progress using Drosophila to better understand age
      related behavioral declines with a focus on age-related locomotor impairment.

PMID- 20800673
TI  - Age-associated plasticity of alpha1-adrenoceptor-mediated tuning of T-cell
      development.
AB  - Alpha(1)-adrenoceptors (alpha(1)-ARs) are involved in neuro-thymic and thymic
      intercellular communications, and consequently modulation of T-cell development.
      Ageing is associated with a number of changes in noradrenergic neuro-effector
      transmission, and possibly intercellular noradrenaline (NA)-mediated
      communication resulting in altered responses of target cells to NA. Thus, in old
      animals an altered NA modulation of thymopoiesis via alpha(1)-ARs may be
      expected. To test this hypothesis, in old and young adult Wistar rats we
      examined: 1) thymic NA levels, density of noradrenergic innervation and NA
      synthesizing cells, as well as alpha(1)-AR expression, and 2) then the effects of
      14-day-long treatment with the alpha(1)-AR blocker, urapidil, on thymocyte
      development. Overall, the first part of study suggested augmented NA signalling
      to thymic cells via alpha(1)-ARs due to increased NA availability and alpha(1)-AR
      thymocyte surface density in old rats. The second part of study supported this
      assumption. Namely, although in rats of both ages urapidil affected the same
      thymocyte developmental steps ultimately leading to changes in the relative
      number of the most mature single positive TCRalphabeta(high) thymocytes, its
      effects were generally more prominent in old animals. Following urapidil
      treatment, the percentages of CD4+CD8- cells, including those showing a
      regulatory CD4+CD25+RT6.1- phenotype, were increased, while CD4-CD8+ cells
      decreased. In old rats, an augmented thymic escape of immature CD4+CD8+ cells was
      also registered. In rats of both ages the thymic changes were accompanied by
      alterations in the proportions of major cell populations in the T-lymphocyte
      compartment of both peripheral blood and spleen, leading to an increase in the
      CD4+/CD8+ T-cell ratio. These alterations were also more pronounced in old rats.
      Moreover, in old rats following urapidil treatment the proportion of
      TCRalphabeta+cells in the periphery was slightly greater reflecting, most likely,
      partly enhanced thymic production of regulatory CD161+TCRalphabeta+cells. Thus,
      the study indirectly suggests an age-associated increase in the basal alpha(1)-AR
      mediated inhibitory influence of NA on thymopoiesis.

PMID- 20800674
TI  - A comparative analysis of liver transcriptome suggests divergent liver function
      among human, mouse and rat.
AB  - The human liver plays a vital role in meeting the body's metabolic needs and
      maintaining homeostasis. To address the molecular mechanisms of liver function,
      we integrated multiple gene expression datasets from microarray, MPSS, SAGE and
      EST platforms to generate a transcriptome atlas of the normal human liver. Our
      results show that 17396 genes are expressed in the human liver. 238 genes were
      identified as liver enrichment genes, involved in the functions of immune
      response and metabolic processes, from the MPSS and EST datasets. A comparative
      analysis of liver transcriptomes was performed in humans, mice and rats with
      microarray datasets shows that the expression profile of homologous genes remains
      significantly different between mouse/rat and human, suggesting a functional
      variance and regulation bias of genes expressed in the livers. The integrated
      liver transcriptome data should provide a valuable resource for the in-depth
      understanding of human liver biology and liver disease.

PMID- 20800675
TI  - Cell proliferation and apoptosis in the olfactory epithelium of the shark
      Scyliorhinus canicula.
AB  - To date, no study has been published on cell renewal in the olfactory epithelium
      of Chondrichthyes. Our work aimed at detecting proliferating cells (by
      Proliferating Cell Nuclear Antigen - PCNA immunohistochemistry) and apoptotic
      cells (by terminal uridine deoxynucleotidyl transferase nick end labeling method)
      in the olfactory epithelium of the shark Scyliorhinus canicula. PCNA
      immunoreactivity and mitotic figures were localized almost exclusively at the
      basal and apical thirds of the epithelial thickness. Double immunofluorescence
      for PCNA and OMP (a marker of mature olfactory neurons) showed that PCNA
      immunoreactivity is lacking in mature olfactory neurons, with the exception of
      crypt neurons. Crypt neurons, a cell type peculiar to fish, often showed PCNA
      immunoreactivity in the nucleus and may be involved in repair processes. The role
      of PCNA in mature crypt neurons requires further investigation to be clarified.
      Apoptosis was observed in sensory neurons and in basal cells. Our data highlight
      the presence of cell proliferation at different levels within the epithelium and
      the occurrence of apoptosis in both mature and proliferating cells.

PMID- 20800676
TI  - Advanced age-related denervation and fiber-type grouping in skeletal muscle of
      SOD1 knockout mice.
AB  - In this study skeletal muscles from 1.5- and 10-month-old Cu/Zn superoxide
      dismutase (SOD1) homozygous knockout (JLSod1(-/-)) mice obtained from The Jackson
      Laboratory (C57Bl6/129SvEv background) were compared with muscles from age- and
      sex-matched heterozygous (JLSod1(+/-)) littermates. The results of this study
      were compared with previously published data on two different strains of Sod1(-/
      ) mice: one from Dr. Epstein's laboratory (ELSod1(-/-); C57Bl6 background) and
      the other from Cephalon, Inc. (CSod1(-/-); 129/CD-1 background). Grouping of
      succinate dehydrogenase-positive fibers characterized muscles of Sod1(-/-) mice
      from all three strains. The 10-month-old Sod1(-/-)C and JL mice displayed
      pronounced denervation of the gastrocnemius muscle, whereas the ELSod1(-/-) mice
      displayed a small degree of denervation at this age, but developed accelerated
      age-related denervation later on. Denervation markers were up-regulated in
      skeletal muscle of 10-month-old JLSod1(-/-) mice. This study is the first to show
      that metallothionein mRNA and protein expression was up-regulated in the skeletal
      muscle of 10-month-old JLSod1(-/-) mice and was mostly localized to the small
      atrophic muscle fibers. In conclusion, all three strains of Sod1(-/-) mice
      develop accelerated age-related muscle denervation, but the genetic background
      has significant influence on the progress of denervation.

PMID- 20800677
TI  - JNK activation is regulated by E2F and promotes E2F1-induced apoptosis.
AB  - Members of the E2F transcription factor family are critical downstream targets of
      the tumor suppressor RB and are often deregulated and hyperactive in human
      tumors. E2F regulates a diverse array of cellular functions including cell
      proliferation and apoptosis. Recent studies indicate that E2F also regulates
      expression of upstream components of pivotal signal transduction pathways,
      thereby modulating the activity of these pathways. We show here that E2F
      modulates the activity of the JNK pathway via E2F-induced upregulation of JNK
      phosphorylation. Accordingly, downregulating E2F1and E2F3 inhibits sustained UV
      induced JNK phosphorylation and ectopic expression of E2F1 or E2F3 induces JNK
      phosphorylation and activation. The mechanism by which E2F modulates JNK
      phosphorylation involves transcriptional induction of the kinase GCK, a MAP4K
      that can activate JNK indirectly. Hence, inhibition of GCK expression impairs
      E2F1-induced JNK phosphorylation. The JNK pathway is an important mediator of
      stress-induced apoptosis and we show here that inhibition of JNK expression or
      activity significantly hinders E2F1-induced apoptosis. Overall, our data identify
      the kinase GCK as a novel E2F-regulated gene and reveal a functional link between
      a central signaling pathway, namely the JNK pathway, and the transcription factor
      E2F.

PMID- 20800678
TI  - Chitosan based delivery systems for mucosal immunization against bovine
      herpesvirus 1 (BHV-1).
AB  - Bovine herpesvirus 1 (BHV-1), is a major pathogen of cattle which causes serious
      infections, including infectious bovine rhinotracheitis (IBR)/infectious pustular
      vulvovaginitis (IPV). At present, BHV-1 is still a serious threat to animal
      health and productivity in Turkey, hence to develop a more efficient and
      economical vaccine system against BHV-1 is certainly an important necessity. A
      mucosal vaccination strategy would provide both mucosal and systemic immune
      responses to protect disease progression and transmission. However, vaccination
      through mucosal membranes requires adjuvants/delivery systems in order to enhance
      the immunogenicity of the antigens. Chitosan, which is a biodegradable,
      biocompatible and bioadhesive natural polysaccharide, has been shown to be
      promising both as a delivery system and an adjuvant for mucosal vaccination. In
      this study, microparticles with appropriate size (<10MUm), positive surface
      charge and high loading efficiency (~95%) were prepared for mucosal delivery of
      BHV-1, using various types of chitosan with different molecular weight and
      solubility. Particles were shown to be taken up by the cells, mostly around the
      nucleus, whereas with aggregates which were bigger in size were adsorbed at the
      surface. Furthermore, gel formulations with a suitable viscosity which would
      provide easy application and remain on the mucosa for extended period of time
      were also developed with a high zeta potential indicating a stable system. Both
      the BHV-1 loaded microparticle and gel formulations were shown to maintain cell
      viability and antigen integrity. Chitosan-based formulations are suggested as
      promising adjuvant/delivery systems for mucosal immunization against BHV-1.

PMID- 20800679
TI  - Pharmacological effect of orally delivered insulin facilitated by multilayered
      stable nanoparticles.
AB  - Intestinal uptake, insulinemia and hypoglycemic effect of orally delivered
      insulin encapsulated in polyelectrolytically stable nanoparticles were evaluated
      in streptozotocin-induced Wistar diabetic rats. Nanoparticles with 396nm mean
      diameter were formed by alginate and dextran sulfate nucleating around calcium
      and binding to poloxamer, stabilized by chitosan, and subsequently coated with
      albumin. The resulting negatively charged nanoparticles retained insulin
      bioactivity and enhanced pharmacological availability by shielding insulin from
      enzymatic degradation and through chemical and physical facilitation of
      permeation through the intestinal membrane. Insulin nanoencapsulated through a
      simplified method avoiding harsh conditions and organic solvents, reduced plasma
      glucose levels to 40% of the basal values with a sustained hypoglycemic effect
      over 24h. Pharmacodynamic and pharmacokinetic parameters were evaluated at a dose
      of 50IU/kg nanoencapsulated insulin, and 13% oral bioavailability showed a
      threefold increase in comparison to free insulin. Confocal microscopy showed
      internalization of nanoencapsulated insulin in the small intestinal mucosa using
      independently labeled insulin-FITC and alginate-RBITC. Therefore the
      nanoformulation facilitated the oral delivery of insulin, and potentially that of
      other therapeutic proteins.

PMID- 20800680
TI  - Long-term stability of sterically stabilized liposomes by freezing and freeze
      drying: Effects of cryoprotectants on structure.
AB  - Liposomes are widely investigated for their use as drug delivery systems, where
      they have to meet strict stability criteria. Hence, it is of common interest to
      establish appropriate storage conditions to improve the shelf life of liposomes.
      In general, long-term stability can be achieved by freezing as well as freeze
      drying, and different carbohydrates or polyalcohols, such as mannitol or glycerol
      are considered as cryoprotective agents to inhibit liposomal fusion or
      degradation during freezing procedures. Here, we determined the impact of
      different cryoprotectants on physicochemical parameters of sterically stabilized
      PEGylated liposomes, which become increasingly important for pharmaceutical
      applications. We investigated particle stability in terms of size, lamellarity
      and thickness of the lipid bilayer using photon correlation spectroscopy and
      small angle X-ray scattering. Besides, we evaluated the impact of cryoprotectants
      on the thermal lipid phase behavior of either frozen/thawn or
      lyophilised/rehydrated PEGylated liposome formulations by differential scanning
      calorimetry. Optimal results for the preservation of the average size of the
      extruded unilamellar liposomes during freezing were achieved using a mixture of
      glycerol and carbohydrate concentrations of about 1% (w/v), irrespective of the
      carbohydrate used. We found no significant changes in the bilayer organisation,
      and the transition behavior of lipids was almost uneffected by freezing. In case
      of freeze-drying, similar carbohydrate concentrations as used for freezing were
      sufficient to maintain the size of PEGylated liposomes after reconstitution of
      the dried lyophilised cakes, but our small angle X-ray scattering data provide
      strong evidence that the lyophilisation/rehydration process affects lipid
      membrane reorganisation on a molecular level such that a swelling of the bilayer
      might occur. These internal structural changes, which are not detected by
      standard particle size analysis, might well influence drug release profiles and
      the pharmacological performance of a liposomal drug delivery system.

PMID- 20800681
TI  - Preservation of viability and antibacterial activity of Lactobacillus spp. in
      calcium alginate beads.
AB  - The objective of the study was to produce calcium alginate beads able to deliver
      Lactobacillus spp. (Lactobacillus plantarum, Lactobacillus rhamnosus GG,
      Lactobacillus bulgaricus and Lactobacillus lactis) with preserved viability and
      antibacterial activity. Four types of beads, containing entrapped (E), surface
      and entrapped (ES), surface (S) and concentrated surface and entrapped
      lactobacilli (C(ES)) were prepared and physically characterized. The
      antibacterial activity of lactobacilli cultures before and after immobilization,
      freeze-drying and throughout storage was studied in relationship to the viable
      number of lactobacilli. Multi-resistant clinical isolates (methicillin-resistant
      Staphylococcus aureus, vancomycine-resistant Enterococcus faecalis, VIM-2-metalo
      beta-lactamase producing Pseudomonas aeruginosa and CTX-M-15-beta-lactamase
      producing strains: Escherichia coli and Klebsiella pneumoniae) were used as
      indicator strains. Alginate beads in which lactobacilli proliferated to the beads
      surface (ES and C(ES)) differed significantly from the other types of beads in
      their physicochemical properties, showing smoother surface morphology, more
      spherical shape, bigger weight, lower calcium content, density and crushing
      force. Lactobacilli cultures, at high cell concentrations (10(8)cfu/ml) were
      active against both Gram-positive and negative multi-resistant bacteria. Beads
      containing both entrapped and surface lactobacilli (ES) resulted in viability and
      antibacterial activity most similar to non-processed lactobacilli cultures. The
      viability and antibacterial activity of the immobilized lactobacilli remained
      stable after 6 months storage.

PMID- 20800682
TI  - The use of dynamic mechanical analysis (DMA) to evaluate plasticization of
      acrylic polymer films under simulated gastrointestinal conditions.
AB  - PURPOSE: Glass transition temperature (T(g)) measurements of polymers are
      conventionally conducted in the dry state with little attention to the
      environment they are designed to work in. Our aim was to develop the novel use of
      dynamic mechanical analysis (DMA) to measure the T(g) of enteric polymethacrylic
      acid methylmethacrylate (Eudragit L and S) polymer films formulated with a range
      of plasticizers in the dry and wet (while immersed in simulated gastric media)
      states. METHODS: Polymer films were fabricated with and without different
      plasticizers (triacetin, acetyl triethyl citrate, triethyl citrate, polyethylene
      glycol, propylene glycol, dibutyl phthalate, dibutyl sebacate). T(g) was measured
      by a dynamic oscillating force with simultaneous heating at 1  degrees C/min.
      This was conducted on films in the dry state and while immersed in 0.1M HCl to
      simulate the pH environment in the stomach. RESULTS: The T(g) of unplasticized
      Eudragit L and S films in the dry state was measured to be 150 and 120  degrees
      C, respectively. These values were drastically reduced in the wet state to 20 and
      71  degrees C for Eudragit L and S films, respectively. The plasticized films
      showed similar falls in T(g) in the wet state. The fall in T(g) of Eudragit L
      films to below body temperature will have far-reaching implications on polymer
      functionality and drug release. CONCLUSIONS: Immersion DMA provides a robust
      method for measuring T(g) of polymer films in the wet state. This allows better
      prediction of polymer behaviour in vivo.

PMID- 20800683
TI  - Increasing cholesterol synthesis in 7-dehydrosterol reductase (DHCR7) deficient
      mouse models through gene transfer.
AB  - Smith-Lemli-Opitz syndrome (SLOS) is caused by deficiency in the terminal step of
      cholesterol biosynthesis: the conversion of 7-dehydrocholesterol (7DHC) to
      cholesterol (C), catalyzed by 7-dehydrocholesterol reductase (DHCR7). This
      disorder exhibits several phenotypic traits including dysmorphia and mental
      retardation with a broad range of severity. There are few proven treatment
      options. That most commonly used is a high cholesterol diet that seems to enhance
      the quality of life and improve behavioral characteristics of patients, although
      these positive effects are controversial. The goal of our study was to
      investigate the possibility of restoring DHCR7 activity by gene transfer. We
      constructed an adeno-associated virus (AAV) vector containing the DHCR7 gene.
      After we infused this vector into affected mice, the introduced DHCR7 gene could
      be identified in liver, mRNA was expressed and a functional enzyme was produced.
      Evidence of functionality came from the ability to partially normalize the serum
      ratio of 7DHC/C in treated animals, apparently by increasing cholesterol
      production with concomitant decrease in 7DHC precursor. By 5 weeks after
      treatment the mean ratio (for 7 animals) had fallen to 0.05 while the ratio for
      untreated littermate controls had risen to 0.14. This provides proof of principle
      that gene transfer can ameliorate the genetic defect causing SLOS and provides a
      new experimental tool for studying the pathogenesis of this disease. If effective
      in humans, it might also offer a possible alternative to exogenous cholesterol
      therapy. However, it would not offer a complete cure for the disorder as many of
      the negative implications of defective synthesis are already established during
      prenatal development.

PMID- 20800684
TI  - Estrogen receptor (ER) subtype agonists alter monoamine levels in the female rat
      brain.
AB  - We assessed the effects of subtype-selective ER agonists on monoamine levels in
      discrete regions of the female rat brain. Ovariectomized (ovx) rats were treated
      for 4 days with vehicle, 17beta-estradiol (E; 0.05mg/kg), an ERbeta agonist (C19;
      3mg/kg) or an ERalpha agonist (PPT; 3mg/kg) and samples from brain regions were
      assessed for monoamines and metabolites. We also assessed effects of ERbeta
      modulation on baseline and fenfluramine-induced release of monoamines in
      hippocampus using microdialysis. In the first study, E and the ERalpha agonist
      increased norepinephrine in cortex and all three ER ligands increased it in the
      ventral hippocampus. Changes in levels of the noradrenergic metabolite, MHPG and
      the dopaminergic metabolite, DOPAC were noted in brain areas of ER ligand-treated
      animals. E also increased levels of 5HIAA in three brain areas. In the
      microdialysis study, there were no differences among groups in baseline levels of
      monoamines. However, E and the ERbeta agonist increased levels of the
      dopaminergic metabolite, HVA following fenfluramine. In summary, activation of
      the two nuclear ERs with selective agonists affects monoamine and metabolite
      levels in discrete brain areas, a number of which are known to play key roles in
      cognitive and affective function.

PMID- 20800685
TI  - Molecular cloning and antiviral activity of IFN-beta promoter stimulator-1 (IPS
      1) gene in Japanese flounder, Paralichthys olivaceus.
AB  - The mitochondrial adaptor, IFN-beta promoter stimulator-1 (IPS-1), also known as
      MAVS/VISA/Cardif, plays a key role in the signal transduction of the RIG-1/MDA5
      pathway to induce the production of interferons (IFNs) and other cytokines. In
      the present study, Japanese flounder (Paralichthys olivaceus) IPS-1 cDNA was
      cloned from Japanese flounder spleen using PCR-based methods. The full-length
      cDNA has 2235 nucleotides and encodes a polypeptide of 641 amino acids. The
      putative Japanese flounder IPS-1 protein contains an N-terminal CARD-like domain,
      a central proline-rich domain, a C-terminal transmembrane domain, and exhibits
      similarity to other teleost counterparts ranging from 20% to 34%. Semi
      quantitative RT-PCR showed that Japanese flounder IPS-1 mRNA was expressed in all
      tissues examined. The expression level of flounder IPS-1 gene was unchanged in
      viral hemorrhagic septicemia virus (VHSV)-infected kidney as measured by
      quantitative real-time PCR (Q-PCR). In addition, Japanese flounder IPS-1
      overexpressing cells were protected against hirame rhabdovirus (HIRRV) and VHSV
      infection as manifested by the delayed appearance of cytopathic effect (CPE) and
      decreased viral titers. Expression of IFN-inducible genes including Mx, ISG15 and
      IRF3 were also induced in the IPS-1-overexpressing cells. These results suggest
      that Japanese flounder IPS-1 is involved in the antiviral immunity as a one of
      the adaptors in fish IFN-activation pathway.

PMID- 20800686
TI  - Linear model decomposition for voltage-sensitive dye imaging signals: application
      in awake behaving monkey.
AB  - Voltage sensitive dye imaging (VSDI) is the only technique that allows to
      directly measure neuronal activity over a large cortical population. It thus
      gives access to the dynamics of lateral interactions within or between cortical
      areas. However, VSDI signal suffers from a weak signal-to-noise ratio and
      processing methods are either rudimentary or dedicated to spatial or temporal
      denoising alone. Here we present an innovative method inspired by fMRI data
      processing, where the goal is to allow, for the first time, denoising of spatio
      temporally inseparable VSDI signals and in the most challenging experimental
      condition, i.e. single trials in awake behaving monkeys. The method is based on a
      linear model (LM) decomposition of individual VSDI trials. The LM was designed
      meticulously by identifying all noise and signal components that are known to
      affect VSDI. We then compared its output against the classical methods based on
      blank division and detrending. LM proved to be significantly much more efficient
      to denoise spatial maps and temporal dynamics compared to these usual techniques.
      It also largely reduced trial-to-trial variability. These performances resulted
      in a four-fold improvement of signal-to-noise ratio and a two-fold increase of
      response detectability. Hence, with this method, fewer trials were needed to
      reach a high signal-to-noise ratio. Lastly, we showed that the LM method can
      accommodate for a large range of response dynamics, a crucial property for
      estimating spatial spread of activity or contrast dynamics. We believe that this
      method will make a strong contribution to imaging dynamics of population
      responses with high spatial and temporal resolution in trial-based experiments of
      awake animals.

PMID- 20800687
TI  - Amygdala responsivity related to memory of emotionally neutral stimuli
      constitutes a trait factor for depression.
AB  - Episodic memory impairment is considered to be a core cognitive deficit of Major
      Depressive Disorder (MDD) and has motivated a line of research investigating the
      role of the amygdala and the hippocampus in depression. While functional
      neuroimaging studies have focused on memory for emotional but not for neutral
      stimuli, in order to probe amygdala function, structural imaging studies have
      tied episodic memory to hippocampal function. We therefore investigated the
      neural correlates of episodic memory formation for neutral stimuli in 20 patients
      with a first depressive episode, 20 patients recovered from a first episode and
      20 healthy controls. Because there is evidence that the amygdala exhibits
      hyperactive responses even to neutral stimuli in depressed subjects, we
      specifically explored the potential role of the amygdala in forming episodic
      memories with neutral content. Both patient groups showed stronger subsequent
      memory effects in the amygdala when compared to controls, in the absence of any
      differences in hippocampal activity between groups. Patients with a first episode
      of MDD showed increased activity related to episodic memory formation in a fronto
      limbic network. These state-related activations may be related to a compensatory
      mechanism, which is supported by the absence of any differences in memory
      performance between groups. These findings represent initial evidence for a
      neurocognitive trait or vulnerability marker of depression-amygdala involvement
      in episodic memory formation of neutral stimuli.

PMID- 20800688
TI  - Regulation of SOX9 in normal and osteoarthritic equine articular chondrocytes by
      hyperosmotic loading.
AB  - OBJECTIVES: SOX9 is a transcription factor that is essential for cartilage
      extracellular matrix (ECM) formation. Osteoarthritis (OA) is characterised by a
      loss of cartilage ECM. In chondrocytes SOX9 gene expression is regulated by
      osmotic loading. Here we characterise SOX9 mRNA regulation through static and
      cyclical application of hyperosmotic conditions in normal and OA monolayer equine
      chondrocytes. Furthermore, we investigate whether extracellular signal-regulated
      protein kinase (ERK)1/2 mitogen-activated protein kinases (MAPK) pathways have a
      role in this regulation of SOX9. METHODS: Equine chondrocytes harvested from
      normal or OA joints were subjected to different osmotic loading patterns as
      either primary (P0) or passaged (P2) cells. The involvement of MEK-ERK signalling
      was demonstrated by using pharmacological inhibitors. In addition SOX9 gene
      stability was determined. Levels of transcripts encoding SOX9, Col2A1 and
      aggrecan were measured using qRT-PCR. De novo glycosaminoglycan synthesis of
      explants was determined with (35)S sulphate during static hyperosmolar loading.
      RESULTS: MEK-ERK signalling increases glycosaminoglycans (GAG) synthesis in
      explants. Static hyperosmotic conditions significantly reduced SOX9 mRNA in
      normal P2 and OA P0 but not normal P0 chondrocytes. SOX9 mRNA was stabilised by
      hyperosmotic conditions. Cyclical loading of normal P2 and OA P0 but not normal
      P0 cells led to an increase in SOX9 gene expression and this was prevented by
      MEK1/2 inhibition. CONCLUSIONS: The response to osmotic loading of SOX9 mRNA is
      dependent on the nature of the osmotic stimulation and the chondrocyte phenotype.
      This variation may be important in disease progression.

PMID- 20800689
TI  - Impact of aerobic exercise training on cognitive functions and affect associated
      to the COMT polymorphism in young adults.
AB  - Physical fitness can serve as a means to enhance cognitive functioning by
      modulating particular aspects of brain functioning. However, mechanisms
      underlying this modulating effect remain widely unresolved. To examine the impact
      and to clarify the mechanisms of physical fitness training in a young and healthy
      population, it was investigated whether an increase in fitness would result in
      improvements in executive control processes and positive and negative affect.
      Moreover, genotype of the Val158Met polymorphism in catechol-O-methyltransferase
      (COMT) as an index of relative central dopamine bioavailability was determined to
      elucidate dopamine tuning efficiency and its association with performance in the
      applied cognitive tasks. Seventy-five individuals participated and underwent an
      incremental fitness test to assess physical fitness. An exercising group
      subsequently engaged in a 17 weeks running training consisting of three running
      sessions at moderate to high, individually adjusted intensities. Associated with
      increased fitness improved cognitive flexibility and cognitive control were
      observed, whereas working memory remained unaffected. In runners, Val/Val
      participants improved cognitive performance to a greater extent compared to
      individuals carrying a Met allele. From the present results it is concluded that
      an increase in physical fitness provides a means to improve cognitive functioning
      via dopaminergic modulation.

PMID- 20800690
TI  - A review of three cases of Clostridium aldenense bacteremia.
AB  - Three cases of Clostridium aldenense bacteremia are reported. C. aldenense is
      also associated with intra-abdominal infections and closely resembles Clostridium
      clostridioforme and therefore may be misidentified. C. aldenense may be a more
      frequent pathogen than appreciated and is generally fluoroquinolone resistant.

PMID- 20800691
TI  - Limbus damage in ocular graft-versus-host disease.
AB  - Graft-versus-host disease (GVHD) is the major cause of morbidity and mortality
      among patients undergoing allogeneic hematopoietic stem cell transplantation.
      Although animal models have been clearly established for the study of skin,
      liver, and gut, currently there is no equivalent experiemental model for
      analyzing ocular involvement, which is rather common, especially among patients
      diagnosed with chronic GVHD. In the current study we have developed a murine
      model of ocular GVHD and, for the first time, we describe the histopathologic
      features involving cornea and limbus, which could play a role in the
      physiopathology of the disease at the ocular level. Our results represent a major
      finding that allows us to define a model for evaluating new therapeutic
      strategies for treating ocular GVHD prior to their use in clinical setting.

PMID- 20800693
TI  - Signaling different pathways of cell death: Abrin induced programmed necrosis in
      U266B1 cells.
AB  - Abrin is a type II ribosome-inactivating protein comprising of two subunits, A
      and B. Of the two, the A-subunit harbours the RNA-N-glycosidase activity and the
      B subunit is a galactose specific lectin that enables the entry of the protein
      inside the cell. Abrin inhibits protein synthesis and has been reported to induce
      apoptosis in several cell types. Based on these observations abrin is considered
      to have potential for the construction of immunotoxin in cell targeted therapy.
      Preliminary data from our laboratory however showed that although abrin inhibited
      the protein synthesis in all cell types, the mode of cell death varied. The aim
      of the present study was therefore to understand different death pathways induced
      by abrin in different cells. We used the human B cell line, U266B1 and compared
      it with the earlier studied T cell line Jurkat, for abrin-mediated inhibition of
      protein translation as well as cell death. While abrin triggered programmed
      apoptosis in Jurkat cells in a caspase-dependent manner, it induced programmed
      necrosis in U266B1 cells in a caspase-independent manner, even when there was
      reactive oxygen species production and loss of mitochondrial membrane potential.
      The data revealed that abrin-mediated necrosis involves lysosomal membrane
      permeabilization and release of cathepsins from the lysosomes. Importantly, the
      choice of abrin-mediated death pathway in the cells appears to depend on which of
      the two events occurs first: lysosomal membrane permeabilization or loss of
      mitochondrial membrane potential that decides cell death by necrosis or
      apoptosis.

PMID- 20800692
TI  - Persistent cognitive and motor deficits after successful antimalarial treatment
      in murine cerebral malaria.
AB  - Human cerebral malaria causes neurological and behavioral deficits which persist
      long after resolution of infection and clearance of parasites with antimalarial
      drugs. Previously, we demonstrated that during active infection, mice with
      cerebral malaria demonstrated negative behavioral outcomes. Here we used a
      chloroquine treatment model of cerebral malaria to determine whether these
      abnormal outcomes would be persistent in the mouse model. C57BL/6 mice were
      infected with Plasmodium berghei ANKA, and treated for ten days. After cessation
      of chloroquine, a comprehensive assessment of cognitive and motor function
      demonstrated persistence of abnormal behavioral outcomes, 10 days after
      successful eradication of parasites. Furthermore, these deficits were still
      evident forty days after cessation of chloroquine, indicating persistence long
      after successful treatment, a hallmark feature of human cerebral malaria. Thus,
      cognitive tests similar to those used in these mouse studies could facilitate the
      development of adjunctive therapies that can ameliorate adverse neurological
      outcomes in human cerebral malaria.

PMID- 20800694
TI  - Cyclic-stretch induces the apoptosis of myoblast by activation of Caspase-3
      protease in a magnitude-dependent manner.
AB  - Although many studies have been performed investigating the effects of mechanical
      stress on the generation and differentiation of myoblasts, little is known about
      the effects of different magnitudes of mechanical stretch on apoptosis in these
      cells. The aim of this study was to investigate the effects of different
      magnitudes of cyclic stretch on apoptosis levels in myoblasts and to investigate
      the possible mechanisms involved. Myoblasts were cultured on flexible membranes
      and subjected to cyclic strain stress in a magnitude-dependent manner (6%, 12% or
      20% surface elongation). Apoptosis rates were evaluated using flow cytometry,
      transmission electron microscopy, and caspase assays. Fas/FasL expression was
      determined by Western blot. The application of different magnitudes of cyclic
      stretch-induced a magnitude-dependent increase in apoptosis and caspase-3
      activity in cultured myoblasts. Furthermore, inhibition of caspase-3 prevented
      stretch-induced apoptosis in myoblasts but did not change Fas and FasL protein
      levels. These data indicate that cyclic stretch induces a magnitude- and caspase
      3-dependent increase of apoptosis in cultured myoblasts in vitro. Mechanical
      forces induced activation of caspase-3 through signalling pathways independent of
      the Fas/FasL system. These results suggest the existence of a novel mechanism for
      the regulation of myoblast apoptosis by cyclic stretch.

PMID- 20800695
TI  - Endoplasmic reticulum targeted Bcl2 confers long term cell survival through
      phosphorylation of heat shock protein 27.
AB  - Overexpression of anti-apoptotic Bcl2 family proteins is often seen in cancers
      rendering them insensitive to apoptosis inducing anticancer strategies. Anti
      apoptotic Bcl2 family proteins are associated with different organelles like
      mitochondria and endoplasmic reticulum (ER) and exert their anti-apoptotic
      activity by inhibiting the release of Cyt.C from mitochondria irrespective of its
      localization. Here, we have identified a long term survival function for Bcl2
      targeted at ER in mammalian system compared to wild type Bcl2 that is mediated by
      enhanced phosphorylation of heat shock protein 27 at ser 15, 78 and 82 sites with
      inhibition of caspase9 activity. Phosphorylation of hsp27 was prevented and the
      survival of ER-Bcl2 cells was reversed by inhibiting p38 and MEK suggesting that
      these kinases can act as the upstream targets for hsp27 phosphorylation. The
      results suggest that Bcl2 possess additional survival function in the regulation
      of apoptosis which is primarily regulated by its association with the ER in an
      hsp27 dependent manner. The interplay of both hsp27 and ER-Bcl2 in providing long
      term survival to cancer cells is interesting since both of these proteins are
      overexpressed in tumors with aggressive phenotype. The results suggest that
      spatial localization of Bcl2 family proteins also play a key role in long term
      survival of cancers indicating another level of functional regulation of Bcl2 in
      cancer cell survival.

PMID- 20800696
TI  - PET tracers for the peripheral benzodiazepine receptor and uses thereof.
AB  - The peripheral benzodiazepine receptor (PBR) is expressed on the outer
      mitochondrial membrane of activated microglia and is implicated in the
      pathophysiology of a variety of central nervous system and peripheral diseases.
      The abundant receptor concentration makes PBR a potential biomarker and an
      attractive target for quantification in vivo using positron emission tomography.
      PBR can be an important target for monitoring disease progression, for evaluating
      the effect of therapy, and for investigating new treatment modalities. PBR is
      also emerging as a potential target in the treatment of neuroinflammatory and
      neuropsychiatric disorders. Here, we review the positron emission tomography
      radioligands employed for imaging PBR in living brain and their applications.

PMID- 20800697
TI  - Improvement of lymphocyte resistance against H(2)O(2)-induced DNA damage in
      Sprague-Dawley rats after eight weeks of a wild blueberry (Vaccinium
      angustifolium)-enriched diet.
AB  - The effect of wild-blueberry consumption on the resistance of H(2)O(2)-induced
      DNA damage was evaluated in the Sprague-Dawley (SD) rat. Thirty-two, four week
      old SD rats were randomly assigned to two groups of sixteen rats each and fed a
      control diet (C) or a wild-blueberry (WB) diet for four or eight weeks. Following
      the dietary treatment, plasma antioxidant capacity was assessed by the TRAP
      assay. Ex vivo protection from H(2)O(2)-induced DNA damage was evaluated in
      lymphocytes by means of the comet assay. No significant effect was detected in
      plasma antioxidant capacity at four and eight weeks in both dietary groups. In
      contrast, the level of DNA damage was significantly lower in rats fed the WB diet
      compared with those on the C diet after eight weeks (11.+/- 1.0% vs 17.2 +/- 2.4%
      DNA in tail, p <= 0.05) but not after four weeks. In conclusion, while WB
      consumption did not affect plasma antioxidant activity, it improved lymphocyte
      protection against oxidative damage, but only after eight weeks.

PMID- 20800698
TI  - Modulation of lipid droplet size and lipid droplet proteins by trans-10,cis-12
      conjugated linoleic acid parallels improvements in hepatic steatosis in obese,
      insulin-resistant rats.
AB  - The isomer-specific effects of conjugated linoleic acid (CLA) on hepatic
      steatosis were assessed in fa/fa Zucker rats, a model for insulin resistance and
      the metabolic syndrome. Eight weeks of feeding trans-10,cis-12 CLA significantly
      improved glucose tolerance without changing body weight or visceral adipose mass.
      The trans-10,cis-12 isomer was also associated with reduced liver lipid content,
      improved liver function and reduced inflammation; these effects were not observed
      in rats fed the cis-9,trans-11 CLA isomer. Reduced liver lipid content did not
      correlate with activation of AMP-activated protein kinase or suppressed
      activation of sterol-regulatory element binding protein-1, two key regulators of
      hepatic lipid metabolism. Interestingly, rats fed cis-9,trans-11 CLA had fewer
      cytoplasmic lipid droplets in hepatocytes compared to rats fed control diet, but
      these droplets were larger in size. Conversely, fa/fa rats fed the trans-10,cis
      12 CLA isomer had greater numbers of hepatic lipid droplets that were smaller in
      size, resulting in overall lower total lipid within these droplets. Changes in
      lipid droplets were associated with lower hepatic levels of PERILIPIN-2 (formerly
      known as adipophilin) in rats fed trans-10,cis-12 CLA, whereas amounts of other
      members of the PERILIPIN family of lipid droplet proteins were unaffected by
      dietary CLA. However, CLA isomers differentially affected the subcellular
      localization of these proteins. Treatment of H4IIE rat hepatoma cells with CLA
      isomers neither prevented nor reversed, but rather induced cytoplasmic lipid
      droplet formation, suggesting that the anti-steatotic effects of trans-10,cis-12
      CLA are likely indirect and potentially mediated via increased lipid utilization
      by peripheral tissues.

PMID- 20800699
TI  - Production and antigenic properties of influenza virus from suspension MDCK
      siat7e cells in a bench-scale bioreactor.
AB  - In efforts to overcome limitations associated with egg-based influenza vaccines,
      mammalian cell substrates have gradually emerged as potential production
      platforms. Recently, a suspension Madin Darby canine kidney (MDCK) cell line for
      influenza virus production was created by expressing the human siat7e gene. To
      examine the broad susceptibility of this novel cell line, the scalability of the
      production process, and the antigenic stability of cell-derived progeny viruses,
      infection experiments using four current influenza vaccine strains
      (A/California/07/2009 X-179A H1N1, A/Brisbane/59/2007 IVR-148 H1N1,
      A/Uruguay/716/2007 X-175C H3N2, and B/Brisbane/60/2008) were performed. In small
      scale experiments, this cell line was found to support high-titer replication of
      all four virus strains. Subsequently, production in a bench-scale bioreactor and
      the antigenic characteristics of progeny viruses were assessed. High titers of
      hemagglutinin (at least 1:512) were produced in a 2-L bench-scale bioreactor with
      all four strains. Immunoblot results demonstrated higher yields in the cells than
      those obtained in chicken embryonated eggs with three of the four tested strains.
      Progeny viruses collected after serial passages in this cell line exhibited
      minimal mutations in the HA-encoding gene. Hemagglutination inhibition (HAI)
      assays using ferret antiserum confirmed the antigenic stability. As a proof-of
      concept this work demonstrates that by using a proper strategy, high yields of
      biologically active hemagglutinin can be produced from scalable cultures of
      suspension MDCK-siat7e cells.

PMID- 20800700
TI  - The efficacy of pneumococcal capsular polysaccharide-specific antibodies to
      serotype 3 Streptococcus pneumoniae requires macrophages.
AB  - The efficacy of antibody immunity against Streptococcus pneumoniae stems from the
      ability of opsonic, serotype (ST)-specific antibodies to pneumococcal capsular
      polysaccharide (PPS) to facilitate killing of the homologous ST by host
      phagocytes. However, PPS-specific antibodies have been identified that are
      protective in mice, but do not promote opsonic killing in vitro, raising the
      question of how they mediate protection in vivo. To probe this question, we
      investigated the dependence of antibody efficacy against lethal systemic
      (intraperitoneal, i.p.) infection with Streptococcus pneumoniae serotype 3 (ST3)
      on macrophages and neutrophils for the following PPS3-specific monoclonal
      antibodies (MAbs) in survival experiments in mice using a non-opsonic human IgM
      (A7), a non-opsonic mouse IgG1 (1E2) and an opsonic mouse IgG1 (5F6). The
      survival of A7- and PPS3-specific and isotype control MAb-treated neutrophil
      depleted and neutrophil-sufficient and macrophage-depleted and macrophage
      sufficient mice were determined after i.p. challenge with ST3 strains 6303 and
      WU2. Neutrophils were dispensable for A7 and the mouse MAbs to mediate protection
      in this model, but macrophages were required for the efficacy of A7 and optimal
      mouse MAb-mediated protection. For A7-treated mice, macrophage-depleted mice had
      higher blood CFU, cytokines and peripheral neutrophil levels than macrophage
      sufficient mice, and macrophage-sufficient mice had lower tissue bacterial
      burdens than control MAb-treated mice. These findings demonstrate that
      macrophages contribute to opsonic and non-opsonic PPS3-specific MAb-mediated
      protection against ST3 infection by enhancing bacterial clearance and suggest
      that neutrophils do not compensate for the absence of macrophages in the model
      used in this study.

PMID- 20800702
TI  - Post-licensure comparison of the safety profile of diphtheria/tetanus/whole cell
      pertussis/haemophilus influenza type b vaccine and a 5-in-1
      diphtheria/tetanus/acellular pertussis/haemophilus influenza type b/polio vaccine
      in the United Kingdom.
AB  - General practitioner consultation data were used to compare the reactogenicity in
      infants of a 5-in-1 acellular pertussis vaccine (DTaP(5)/Hib/IPV) introduced in
      the United Kingdom in 2004 to the 4-in-1 whole cell-pertussis vaccine (DTwP/Hib)
      that it replaced. For each vaccine the incidence in the week following
      vaccination was compared to other periods to obtain a relative incidence. A lower
      relative incidence of crying, fever and local reactions was seen with
      DTaP(5)/Hib/IPV than DTwP/Hib. Although there were no other significant
      differences between vaccines the relative incidence was significantly above one
      on the day of vaccination for convulsions following DTwP/Hib and for
      apnoea/collapse following DTaP(5)/Hib/IPV.

PMID- 20800703
TI  - Genetics, development and composition of the insect head--a beetle's view.
AB  - Many questions regarding evolution and ontogeny of the insect head remain open.
      Likewise, the genetic basis of insect head development is poorly understood.
      Recently, the investigation of gene expression data and the analysis of
      patterning gene function have revived interest in insect head development. Here,
      we argue that the red flour beetle Tribolium castaneum is a well suited model
      organism to spearhead research with respect to the genetic control of insect head
      development. We review recent molecular data and discuss its bearing on early
      development and morphogenesis of the head. We present a novel hypothesis on the
      ontogenetic origin of insect head sutures and review recent insights into the
      question on the origin of the labrum. Further, we argue that the study of
      developmental genes may identify the elusive anterior non-segmental region and
      present some evidence in favor of its existence. With respect to the question of
      evolution of patterning we show that the head Anlagen of the fruit fly Drosophila
      melanogaster and Tribolium differ considerably and we review profound differences
      of their genetic regulation. Finally, we discuss which insect model species might
      help us to answer the open questions concerning the genetic regulation of head
      development and its evolution.

PMID- 20800701
TI  - Antibody response to Haemophilus influenzae outer membrane protein D, P6, and
      OMP26 after nasopharyngeal colonization and acute otitis media in children.
AB  - Development of natural antibodies to 3 nontypeable Haemophilus influenzae (NTHi)
      outer membrane proteins (D, P6 and OMP26) was prospectively studied in 130
      children 6-30 months of age during NP colonization and acute otitis media (AOM).
      IgG antibody to protein D, P6 and OMP26 increased with age (p<0.001). Serum IgG
      responses to NP colonization were different for the 3 proteins: protein D
      responses occurred at a later age than P6, and OMP26 responses were minimal. For
      all 3 proteins serum antibody levels in the convalescent phase of AOM infection
      were not as high as after NP colonization. Antibodies to protein D and P6 but not
      OMP26 were bactericidal.

PMID- 20800704
TI  - Challenges and responsibilities for public sector scientists.
AB  - Current agriculture faces the challenge of doubling food production to meet the
      food needs of a population expected to reach 9 billion by mid-century whilst
      maintaining soil and water quality and conserving biodiversity. These challenges
      are more overwhelming for the rural poor, who are the custodians of environmental
      resources and at the same time particularly vulnerable to environmental
      degradation. Solutions have to come from concerted actions by different segments
      of society in which public sector science plays a fundamental role. Public sector
      scientists are at the root of all the present generation of GM crop traits under
      cultivation and more will come with the new knowledge that is being generated by
      systems biology. To speed up innovation, molecular biologists must interact with
      scientists from the different fields as well as with stakeholders outside the
      academic world in order to create an environment capable of capturing value from
      public sector knowledge. I highlight here the measures that have to be taken
      urgently to guarantee that science and technology can tackle the problems of
      subsistence farmers.

PMID- 20800705
TI  - Wheat germ cell-free protein production system for post-genomic research.
AB  - Genomic information becomes useful knowledge only when the structures and
      functions of gene products are understood. In spite of a vast array of analytical
      tools developed for biological studies in recent years, producing proteins at
      will is still a bottleneck in post-genomic studies. The cell-free protein
      production system we developed using wheat embryos has enabled us to produce high
      quality proteins for genome-wide functional and structural analyses and at the
      same time circumvent almost all the limitations, such as biohazards and costs,
      that have hampered conventional cell-free protein synthesis systems. In the
      present article, we introduce examples of our new wheat germ cell-free protein
      production system and its application to functional and structural analyses, with
      the focus on the former.

PMID- 20800706
TI  - In the cauldron of cell-free synthesis of membrane proteins: playing with new
      surfactants.
AB  - Cell-free protein synthesis is a well-known technique for the roles it has played
      in deciphering the genetic code and in the beginnings of signal sequence studies.
      Since then, many efforts have been made to optimise this technique and, recently,
      to adapt it to membrane protein production with yields compatible with structural
      investigations. The versatility of the method allows membrane proteins to be
      obtained directly stabilised in surfactant micelles or inserted in a lipidic
      environment (proteoliposome, bicelle, and nanodisc) at the end of synthesis.
      Among the surfactants used, non-detergent ones such as fluorinated surfactants
      proved to be a good alternative in terms of colloidal stability and preservation
      of the integrity of membrane proteins, as shown for Escherichia coli homo
      pentameric channel, MscL (Park et al., Biochem. J., 403: 183-187). Here we report
      cell-free expression of Escherichia coli leader peptidase (a transmembrane
      protease), Halobacterium salinarium bacteriorhodopsin (a transmembrane protein
      binding a hydrophobic cofactor) and E. coli MscL in the presence of non-detergent
      surfactants, amphipols and fluorinated surfactants in comparison to their
      expression in classical detergents. The results confirm the potentialities of
      fluorinated surfactants and, although pointing to limitations in using the first
      generations amphipols, results are discussed in the light of membrane protein
      refolding, especially in the case of bacteriorhodopsin. Preliminary experiments
      using new generations of amphipols supports choices made in developing new
      molecules.

PMID- 20800709
TI  - Linker histone subtypes are not generalized gene repressors.
AB  - Antibodies to the six chicken histone H1 subtypes and the variant histone H5 have
      been used in immunoprecipitations of crosslinked chromatin fragments (xChIPs) to
      map linker histones across the beta-globin locus and the widely expressed
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and carbonic anhydrase (CA)
      genes in three cell types: 15-day embryo chicken erythrocytes, 15-day embryo
      chicken brain and the early erythroid cell line HD24. In erythrocytes, where the
      beta-adult and beta-hatching genes are active, the H1.01, H1.11L and H1.11R
      subtypes are substantially depleted throughout the beta-globin locus and the
      neighboring heterochromatin, in contrast to the other four subtypes, in
      particular the more abundant H5. Active genes therefore carry high levels of some
      but not all linker histone subtypes. The situation is similar in HD24 cells,
      except that substantial depletions are found at the promoters of the adult
      beta(A) and embryonic beta(rho) and beta(epsilon) genes, despite these genes not
      yet being active in HD24 cells. The distributions in the brain tissue are
      characterised by the absence of H1.02, H1.03 and H5 from the hypersensitive site
      HS3 and from the beta-adult 3' enhancer for the H1.11L and H1.11R subtypes. The
      data show that although linker histone subtypes play distinct cell-type specific
      roles in gene regulation, their widespread distribution indicates they are not
      intrinsically inhibitory to basic chromatin transactions.

PMID- 20800710
TI  - Comprehensive analysis of elastase-induced pulmonary emphysema in mice: effects
      of ambient existing particulate matters.
AB  - Pulmonary exposure of rodents to porcine pancreatic elastase (PPE) induces
      lesions that morphologically resemble human panacinar emphysema. However, there
      has been little work on the comprehensive analysis of this model. The present
      study was designed to extensively examine the biological effects of PPE on
      inflammation, cell damage, emphysematous change, and cholinergic reactivity in
      the lungs of mice. Furthermore, we evaluated the effects of pulmonary exposure to
      diesel exhaust particles (DEP) on the disease model. Intratracheal administration
      of PPE induced (1) proinflammatory response in the lungs that was characterized
      by significant infiltration of leukocytes such as macrophages, eosinophils, and
      lymphocytes and an increased level of interleukin-1beta in lung homogenates, (2)
      lung cell damage, indicated by higher levels of total protein, lactate
      dehydrogenase, and alkaline phosphatase in lung homogenates, (3) emphysema
      related morphological changes including airspace enlargement and progressive
      destruction of alveolar wall structures, and (4) airway responsiveness to
      methacholine in the context of the compliance value of the respiratory system in
      a dose-dependent manner showing an overall trend. A single intratracheal
      administration of DEP did not significantly facilitate the hallmark of the
      disease. This is the first study to extensively analyze PPE-induced lung
      emphysema in mice with evaluation of the effects of DEP. Furthermore, this
      bioassay may be applied to future investigations that evaluate new therapeutic
      agents or risk factors for pulmonary emphysema.

PMID- 20800711
TI  - Influence of dipyridamole and its combination with NO donor or NO synthase
      inhibitor on adjuvant arthritis.
AB  - The anti-arthritic and anti-inflammatory effects of dipyridamole and the possible
      involvement of NO in the dipyridamole action are not yet clear. The aim of this
      study was to evaluate the effects of dipyridamole alone and in combination with
      either the nitric oxide donor, sodium nitroprusside (SNP) or the non-selective
      nitric oxide synthase inhibitor, L-NG- monomethyl arginine (L-NMMA), on
      pathogenesis of adjuvant-induced arthritis model in rats. The results of the
      present work showed that prophylactic administration of dipyridamole alone and
      dipyridamole administration in combination with either low dose of SNP or L-NMMA
      significantly ameliorated pathogenesis of adjuvant arthritis in rats as evidenced
      by significant decrease in arthritis index, hind paws volume, loss of body
      weight, hyperalgesia compared with control vehicle (1% DMSO) treated adjuvant
      arthritic rats. Inflammatory cellular infiltrate in synovium of ankle joint and
      pannus formation were also markedly inhibited. Interleukin-10(IL-10) levels were
      significantly increased in these groups of animals. In contrast, a high dose of
      SNP counteracted the anti-inflammatory and anti-arthritic effects of
      dipyridamole. The inhibitory effect of therapeutic administration of dipyridamole
      alone on adjuvant arthritis syndrome was not significantly different from that of
      vehicle administration. In conclusion, dipyridamole has prophylactic but not
      therapeutic anti-arthritic and anti-inflammatory effects that appear to be
      dependent on inhibition of NO synthase. A synergistic combination between
      dipyridamole and NO synthase inhibitor or low dose of NO donor may have
      prophylactic and therapeutic values in autoimmune diseases like RA.

PMID- 20800712
TI  - A left circum-aortic renal vein aneurysm.
AB  - A well-defined, slow-flowing vascular lesion was found incidentally by Doppler
      abdominal sonography in the left renal hilar region of a 36-year-old Taiwanese
      woman. Clinically, the physical examination and laboratory screening were
      unremarkable. A magnetic resonance angiography of the area near the renal hilum
      showed a saccular mass (3.5 x 3.1 x 2.5 cm) embracing the aorta by the anterior
      and posterior branch of the aneurysm originating from the left renal vein to the
      inferior vena cava. However, the patient refused further invasive intervention
      and has since been examined periodically by ultrasonography for 18 months without
      increasing size or symptoms.

PMID- 20800707
TI  - Distinct regulatory mechanisms of eukaryotic transcriptional activation by SAGA
      and TFIID.
AB  - A growing number of human diseases are linked to abnormal gene expression which
      is largely controlled at the level of transcriptional initiation. The gene
      specific activator promotes the initiation of transcription through its
      interaction with one or more components of the transcriptional initiation
      machinery, hence leading to stimulated transcriptional initiation or activation.
      However, all activator proteins do not target the same component(s) of the
      transcriptional initiation machinery. Rather, they can have different target
      specificities, and thus, can lead to distinct mechanisms of transcriptional
      activation. Two such distinct mechanisms of transcriptional activation in yeast
      are mediated by the SAGA (Spt-Ada-Gcn5-Acetyltransferase) and TFIID
      (Transcription factor IID) complexes, and are termed as "SAGA-dependent" and
      "TFIID-dependent" transcriptional activation, respectively. SAGA is the target of
      the activator in case of SAGA-dependent transcriptional activation, while the
      targeting of TFIID by the activator leads to TFIID-dependent transcriptional
      activation. Both the SAGA and TFIID complexes are highly conserved from yeast to
      human, and play crucial roles in gene activation among eukaryotes. The regulatory
      mechanisms of eukaryotic transcriptional activation by SAGA and TFIID are
      discussed here. This article is part of a Special Issue entitled The 26S
      Proteasome: When degradation is just not enough!

PMID- 20800708
TI  - Structure characterization of the 26S proteasome.
AB  - In all eukaryotic cells, 26S proteasome plays an essential role in the process of
      ATP-dependent protein degradation. In this review, we focus on structure
      characterization of the 26S proteasome. Although the progress towards a high
      resolution structure of the 26S proteasome has been slow, the recently solved
      structures of various proteasomal subcomplexes have greatly enhanced our
      understanding of this large machinery. In addition to having an ATP-dependent
      proteolytic function, the 26S proteasome is also involved in many non-proteolytic
      cellular activities, which are often mediated by subunits in its 19S regulatory
      complex. Thus, we include a detailed discussion of the structures of 19S
      subunits, including proteasomal ATPases, ubiquitin receptors, deubiquitinating
      enzymes and subunits that contain PCI domain. This article is part of a Special
      Issue entitled The 26S Proteasome: When degradation is just not enough!

PMID- 20800713
TI  - Eversion endarterectomy of the internal carotid artery combined with open
      endarterectomy of the common carotid artery.
AB  - The author presents a technique for endarterectomy and reconstruction of the
      carotid bifurcation in difficult cases when the plaque extends high into the
      internal carotid artery. The technique combines the aspects of the 2 most
      commonly performed procedures: carotid endarterectomy after a longitudinal
      arteriotomy extending from the common carotid artery into the internal carotid
      artery and eversion endarterectomy in which the plaque is removed from the
      internal carotid artery sectioned from the common carotid artery and everted. The
      author suggests applying this technique selectively in patients in whom the
      atherosclerotic plaque extends very high into the internal carotid artery. The
      technique offers the advantages of removing the plaque into the common carotid
      artery under direct vision and leaving the original dimensions and geometry of
      the internal carotid artery, theoretically decreasing the probability of early
      thrombosis and recurrent carotid disease. For routine cases, the author prefers
      and recommends standard carotid bifurcation endarterectomy with patch closure
      when the size of the arteries is reduced like in women and selected male
      patients.

PMID- 20800714
TI  - Post-appendectomy visits to the emergency department within the global period: a
      target for cost containment.
AB  - BACKGROUND: Postoperative visits to the emergency department (ED) instead of the
      surgeon's office consume enormous cost. HYPOTHESIS: Postoperative ED visits can
      be avoided. SETTING: Fully accredited, single-institution, 617-bed hospital
      affiliated with the University of Connecticut School of Medicine. PATIENTS:
      Retrospective analysis of 597 consecutive patients with appendectomies over a 4
      year period. METHODS: Demographic and medical data, at initial presentation,
      surgery, and ED visit were recorded as categorical variables and statistically
      analyzed (Pearson chi(2) test, Fisher exact test, and linear-by-linear). Costs
      were calculated from the hospital's billing department. RESULTS: Forty-six
      patients returned to the ED within the global period with pain (n = 22, 48%),
      wound-related issues (n = 6, 13%), weakness (n = 4, 9%), fever (13%), and nausea
      and vomiting (n = 3, 6%). Thirteen patients (28%) required readmission.
      Predictive factors for ED visit postoperatively were perforated appendicitis (2
      fold increase over uncomplicated appendicitis) and comorbidities (cardiovascular
      or diabetes). The cost of investigations during ED visits was $55,000 plus
      physician services. CONCLUSIONS: ED visits during the postoperative global period
      are avoidable by identifying patients who may need additional care; improving
      patient education, optimizing pain control, and improving patient office access.

PMID- 20800715
TI  - The use of laparoscopic surgery in pregnancy: evaluation of safety and efficacy.
AB  - BACKGROUND: Laparoscopic surgery in pregnant women has become increasingly more
      common since the 1990s; however, the safety of laparoscopy in this population has
      been widely debated, particularly in emergent and urgent situations. METHODS: A
      retrospective chart review of all pregnant women following a nonobstetric
      abdominal operation at a University hospital between 1993 and 2007. Perioperative
      morbidity and mortality for the mother and fetus were evaluated. RESULTS: Ninety
      four subjects were identified; 53 underwent laparoscopic procedures and 41
      underwent open procedures. Cholecystectomy and appendectomy were performed in
      both groups with salpingectomy/ovarian cystectomy only in the laparoscopic group.
      No maternal deaths occurred, while fetal loss occurred in 3 cases within 7 days
      of the operation and in 1 case 7 weeks postoperatively. This and other perinatal
      complications occurred in 36.7% of the laparoscopic group and 41.7% of the open
      group. CONCLUSION: Laparoscopic appendectomy and cholecystectomy appear to be as
      safe as the respective open procedures in pregnant patients; however, this
      population in particular remains at risk for perinatal complications regardless
      of the method of abdominal access.

PMID- 20800717
TI  - Parenteral nutrition: a clear and present danger unabated by tight glucose
      control.
AB  - BACKGROUND: The infectious risks of parenteral nutrition (PN) in critical illness
      are well described, although most literature predates tight glucose control (TGC)
      practice. The authors hypothesized that PN-related complications are ameliorated
      by TGC and are equivalent to those in enteral nutrition (EN) patients. METHODS: A
      prospective cohort study of patients admitted to the surgical intensive care unit
      was conducted, comparing PN and EN patients. TGC target was 80 to 110 mg/dL.
      Univariate and multivariate logistic regression was used to explore the
      association between infectious outcomes and PN use. RESULTS: One hundred fifty
      five patients were studied. Mean daily glucose values were lower for the PN group
      than for the EN patients (118.2 vs 125.6 mg/dL, P = .002). Nonetheless, the
      incidence of bloodstream infection and catheter-related bloodstream infection was
      significantly associated with the administration of PN. In a multivariate
      logistic regression model, PN was associated with a >4-fold increase in the odds
      of having a catheter-related bloodstream infection (odds ratio, 4.48; 95%
      confidence interval, 1.14-17.49; P = .03). CONCLUSIONS: Despite the successful
      implementation of TGC, PN is still a significant risk factor for infectious
      complications among surgical intensive care unit patients.

PMID- 20800716
TI  - The clinical impact and outcomes of immunohistochemistry-only metastasis in
      breast cancer.
AB  - BACKGROUND: Modern surgical and pathological techniques can detect small-volume
      axillary metastases in breast cancer with unknown clinical significance. METHODS:
      A retrospective database review from 1996 through 2004 identified all patients
      with immunohistochemical (IHC)-only sentinel node (IHC-SN) metastases and
      compared them with negative controls (Neg-SN). RESULTS: When comparing the 232
      IHC-SN patients with the 252 Neg-SN controls, the IHC-SN patients had larger
      tumors, more lobular histology, a higher grade, and more HER2/neu positivity.
      They also received more systemic therapy. With a median follow-up of 5 years,
      there were no differences in recurrence-free survival or overall survival. In 123
      IHC-SN patients treated with axillary dissection (axillary lymph node
      dissection), 16% had positive non-SLNs. Patients with positive non-SLNs tended to
      have worse outcomes. CONCLUSIONS: IHC-only sentinel lymph node (SLN) metastases
      were associated with worse prognostic features and higher rates of systemic
      therapy. However, no outcomes differences were noted.

PMID- 20800718
TI  - Biomechanical analysis of polypropylene prosthetic implants for hernia repair: an
      experimental study.
AB  - BACKGROUND: Although polypropylene (PP) is the most common biomaterial used for
      ventral and inguinal hernia repairs, its mechanical properties remain obscure.
      METHODS: Retraction, solidity, and elasticity of 3 large pore-size monofilament
      PP prostheses, 1 heavy-weight PP (HWPP), a second low-weight PP, and a third
      coated with atelocollagen were evaluated in a rabbit incisional hernia model. A
      small pore-size multifilament PP implant (MPP) also was tested. RESULTS: Unlike
      pore size, the weight of the prosthesis was not an influencing factor for
      retraction. Atelocollagen coating reduced retraction (P < .05). HWPP and MPP were
      less likely to rupture (P < .05). HWPP had comparatively better elasticity (P <
      .05), whereas MPP supported the greatest elastic force (P < .05). Nevertheless,
      the amount of shrinkage of MPP (30% of the original size) made this prosthesis
      unusable. CONCLUSIONS: In this study, HWPP presented the most advantageous
      biomechanical compromise for hernia surgery.

PMID- 20800719
TI  - Invited commentary on "Duration of deep vein thrombosis prophylaxis in the
      surgical patient and its relation to quality issues" by Muntz.

PMID- 20800720
TI  - Determination of polybrominated diphenyl ethers in fish tissues by matrix solid
      phase dispersion and gas chromatography coupled to triple quadrupole mass
      spectrometry: case study on European eel (Anguilla anguilla) from Mediterranean
      coastal lagoons.
AB  - This paper describes the development and validation of an analytical methodology
      to determine 28 polybrominated diphenyl ethers (PBDEs) in European eel (Anguilla
      anguilla) tissues using matrix solid-phase dispersion (MSPD) and gas
      chromatography coupled to triple quadrupole mass spectrometry (GC-QQQ-MS/MS). A
      total of 28 PBDEs were targeted, including tri- to deca-brominated congeners. The
      robustness and effectiveness of the proposed sample preparation procedure was
      demonstrated in lipid-rich eel tissues. The use of batch MSPD with activated
      silica gel and H(2)SO(4)-impregnated silica gel, followed by H(2)SO(4) digestion
      and multilayer cartridge clean-up allowed for complete lipid removal and
      eliminated matrix effects during GC-QQQ-MS/MS analysis. The average PBDE
      recoveries from eel muscle samples spiked with PBDEs at two levels were in the
      range 56.2-119.0%. Precision was satisfactory since relative standard deviations
      were lower than 19.6%, regardless of spike level, and method quantification
      limits ranged between 1 and 170 pg g(-1) (wet weight). The method demonstrated
      its successful application for the analysis of eel samples from two coastal
      lagoons located on the western French Mediterranean coast. All samples tested
      positive, but for tri- to hexa-brominated congeners only and total PBDE levels
      observed in this study were in the range 0.08-1.80 ng g(-1) wet weight.

PMID- 20800721
TI  - Stochastic nanopore sensors for the detection of terrorist agents: current status
      and challenges.
AB  - Nanopore stochastic sensor works by monitoring the ionic current modulations
      induced by the passage of analytes of interest through a single pore, which can
      be obtained from a biological ion channel by self-assembly or artificially
      fabricated in a solid-state membrane. In this minireview, we overview the use of
      biological nanopores and artificial nanopores for the detection of terrorist
      agents including explosives, organophosphorus nerve agents, nitrogen mustards,
      organoarsenic compounds, toxins, and viruses. We also discuss the current
      challenge in the development of deployable nanopore sensors for real-world
      applications.

PMID- 20800722
TI  - Assessment of accuracy and precision in speciation analysis by competitive ligand
      equilibration-cathodic stripping voltammetry (CLE-CSV) and application to
      Antarctic samples.
AB  - The analytical performances of Competitive Ligand Equilibration with Cathodic
      Stripping Voltammetric detection of the labile fraction (CLE-CSV) were assessed.
      This speciation method enables the concentration of natural ligand(s) and their
      conditional stability constants for the complexation of the investigated metal to
      be determined through thermodynamic considerations. Literature data were
      discussed and general trends in the precision of the determined parameters
      identified: ligand concentrations were affected, on average, by a 10% relative
      percentage standard deviation (RSD%), whereas conditional stability constants
      showed much lower precision, with an average RSD% of 50%. New experimental data
      were collected to obtain a complete assessment of accuracy and precision
      attainable for the determination of strong ligands at the ultra trace level,
      enabling the whole protocol to be evaluated. Firstly, the side reaction
      coefficient alpha for the formation of the complex between the added ligand and
      the investigated metal (alpha(CuL)) was determined. The method was subsequently
      applied to the analysis of solution containing ligand at trace levels (5-50 nM)
      with known complexing characteristics. Copper was used as the model metal ion and
      ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid
      (DTPA) as the model ligands. Results evidenced that the CLE-CSV protocol is not
      affected by systematic errors in the determination of both ligand concentration
      and the conditional stability constants. Good precision is obtained for ligand
      concentrations, with an average relative standard deviation (RSD%) of 5%; an
      average RSD% of 23% was calculated for the conditional stability constants.
      Including the contribution of the uncertainty in the value of alpha(CuL) in the
      evaluation of the uncertainty in the latter parameter increased the RSD% up to
      40%. The CLE-CSV protocol was subsequently applied to the detection of strong
      ligands in water samples collected in Antarctica: precision was shown to be
      comparable with literature data.

PMID- 20800723
TI  - An amperometric method for the detection of amitrole, glyphosate and its
      aminomethyl-phosphonic acid metabolite in environmental waters using passive
      samplers.
AB  - The herbicides amitrole and glyphosate, and its metabolite aminomethyl-phosphonic
      acid (AMPA), in water samples have been directly analysed by high-performance
      liquid chromatography using an electrochemical (EC) detector. Limits of detection
      of 0.3 microg mL(-1) for glyphosate, 0.05 microg mL(-1) for AMPA and 0.03 microg
      mL(-1) for amitrole were comparable to those obtained by other authors using EC
      and also by liquid chromatography coupled to mass spectrometry, but the latter
      method requires derivatisation and pre-concentration of the sample whereas EC
      methods show similar sensitivity without the need of any derivatisation. The
      method was specifically designed to analyse extracts from passive samplers used
      for monitoring of polar herbicide residues in waters. To this purpose, three
      types of Empore disks were tested for their ability to adsorb and desorb these
      ionic, polar analytes. A procedure for their extraction from the membranes and
      reducing the interferences from other substances present in natural waters (i.e.
      humic acids) is described. The method is simple, does not require sophisticated
      equipment and is valid for the analysis and monitoring of herbicides residues
      using passive samplers.

PMID- 20800724
TI  - Micro-solid phase extraction coupled with high-performance liquid chromatography
      tandem mass spectrometry for the determination of stimulants, hallucinogens,
      ketamine and phencyclidine in oral fluids.
AB  - A confirmatory method for the determination of illicit drugs based on micro-solid
      phase extraction with modified tips, made of a functionalized fiberglass with
      apolar chains of octadecylsilane into monolithic structure, has been developed in
      this study. Drugs belonging to different chemical classes, such as amphetamine,
      methamphetamine, methylenedioxyamphetamine, methylenedioxyethylamphetamine,
      methylenedioxymethylamphetamine, cocaine, benzoylecgonine, ketamine, mescaline,
      phencyclidine and psilocybine were analyzed. The quantitation was performed by
      liquid chromatography-tandem mass spectrometry and the analytes were detected in
      positive ionization by means of an electrospray source. The limits of
      quantification ranged between 0.3 ng mL(-1) for cocaine and 4.9 ng mL(-1) for
      psilocybine, with coefficients of determination (r(2)) >0.99 for all the analytes
      as recommended in the guidelines of Society of Forensic Toxicologists-American
      Association Forensic Sciences.

PMID- 20800725
TI  - Development of an immunoassay and a sol-gel-based immunoaffinity cleanup method
      for coplanar polychlorinated biphenyls from soil and sediment samples.
AB  - Two polychlorinated biphenyls (PCB) enzyme linked immunosorbent assays (ELISAs)
      were developed using goat PCB purified immunoglobulin (IgG) antibodies (Abs). The
      IgGs exhibited the highest affinity toward PCB-77 (24 ng mL(-1)) with
      sensitivities in the range of 6-11 ng mL(-1). The Abs cross-reacted with PCB-126
      and the heptachlorodibenzofuran 1,2,3,4,6,7,8-HpCDF but not with PCB-169, PCB
      118, Aroclor 1232, 1248, 1260 or the hexachlorodibenzofuran 2,3,4,6,7,8-HxCDF.
      The IgGs were also used to develop a sol-gel-based immunoaffinity purification
      (IAP) method for cleanup of PCB-126. Recovery efficiencies depended on the sol
      gel formats; a 1:12 format resulted in the highest binding capacity. Net binding
      capacity ranged from 112 to 257 ng, and 90% of the analyte could be eluted with
      only 2 mL of ethanol. The method was also very efficient in purifying PCB-126
      from spiked soil and sediment samples from contaminated sites; and eliminating
      matrix interferences to a degree that enabled analysis of the purified samples by
      ELISA. The approaches developed in the course of the study form a basis for the
      development of additional IAP methods for other PCBs, and their implementation in
      high-throughput screening programs for PCB in food, soil, and other environmental
      and biological samples.

PMID- 20800726
TI  - Quantification of 2-acetyl-1-pyrroline in rice by stable isotope dilution assay
      through headspace solid-phase microextraction coupled to gas chromatography
      tandem mass spectrometry.
AB  - A new and convenient synthesis of 2-acetyl-1-pyrroline (2AP), a potent flavor
      compound in rice, and its ring-deuterated analog, 2-acetyl-1-d(2)-pyrroline (2AP
      d(2)), was reported. A stable isotope dilution assay (SIDA), involving headspace
      solid-phase microextraction (HS-SPME) combined with gas chromatography-positive
      chemical ionization-ion trap-tandem mass spectrometry (GC-PCI-IT-MS-MS), was
      developed for 2AP quantification. A divinylbenzene/carboxen/polydimethylsiloxane
      (DVB/CAR/PDMS) fiber was used for HS-SPME procedure and parameters affecting
      analytes recovery, such as extraction time and temperature, pH and salt, were
      studied. The repeatability of the method (n=10) expressed as relative standard
      deviation (RSD) was 11.6%. A good linearity was observed from 5.9 to 779 ng of
      2AP (r(2)=0.9989). Limits of detection (LOD) and quantification (LOQ) for 2AP
      were 0.1 and 0.4 ng g(-1) of rice, respectively. The recovery of spiked 2AP from
      rice matrix was almost complete. The developed method was applied to the
      quantification of 2AP in aerial parts and grains of scented and non-scented rice
      cultivars.

PMID- 20800727
TI  - Application of enzymatic probe sonication extraction for the determination of
      selected veterinary antibiotics and their main metabolites in fish and mussel
      samples.
AB  - A new method based on enzymatic probe sonication extraction prior to high
      performance liquid chromatography (HPLC) has been developed for the determination
      of 11 antibiotics (drugs) and the main metabolites of five of them in fish tissue
      and mussel samples. The analytes belong to four different classes of antibiotics
      (sulfonamides, tetracyclines, penicillins and amphenicols). The analysed
      compounds were sulfadiazine (SDI) and N(4)-acetylsulfadiazine (NDI) metabolite,
      sulfamethazine (SMZ) and N(4)-acetylsulfamethazine (NMZ), sulfamerazine (SMR) and
      N(4)-acetylsulfamerazine (NMR), sulfamethoxazole (SMX), trimetroprim (TMP),
      amoxicillin (AMX) and its main metabolite amoxicilloic acid (AMA), ampicillin
      (AMP) and its main metabolite ampicilloic acid (APA), chloramphenicol (CLF),
      thiamphenicol (TIF), oxytetracycline (OXT) and chlortetracycline (CLT). The main
      factors affecting the extraction efficiency (type of enzyme, type and volume of
      extractant, ultrasounds power and extraction time) were optimised in tissue of
      hake (Merluccius merluccius), anchovy (Engraulis encrasicolus), mussel (Mytilus
      sp.) and wedge sole (Solea solea). The extraction was carried out using an
      extraction time of 5 min with 5 mL of water and subsequent clean-up with
      dichloromethane. High-performance liquid chromatography (HPLC) with diode array
      (DAD) and fluorescence (FLD) detectors was used for the determination of the
      antibiotics. The separation of the analysed compounds was conducted by means of a
      Phenomenex Gemini C(18) (150 mm x 4.6 mm I.D., particle size 5 microm) analytical
      column with LiChroCART LiChrospher C(18) (4 mm x 4 mm, particle size 5 microm)
      guard-column. Analysed drugs were determined using formic acid 0.1% (v/v) in
      water and acetonitrile in gradient elution mode as mobile phase. The proposed
      method was also evaluated by a laboratory assay consisting of the determination
      of the targeted analytes in samples of Cyprinus carpio which had previously
      administered the antibiotics.

PMID- 20800728
TI  - Quantum dot based probing of mannitol: an implication in clinical diagnostics.
AB  - We demonstrate that mannitol, an important diuretic, can be determined with
      cysteine-capped CdS quantum dots (QDs) using optical spectroscopy. Unique
      luminescence enhancement of QDs was observed on interaction with mannitol. The
      binding between QDs and mannitol was monitored by UV-vis, Fourier transform infra
      red and Raman spectroscopy. The binding constant was determined following the
      Langmuir binding isotherm. A quantitative correlation between mannitol
      concentration and PL enhancement of CdS QDs has been established. We also
      observed that possible interfering agents, such as, urea, uric acid, creatinine,
      some metal ions, glucose, sorbitol or sucrose had no significant effect on
      luminescence of CdS QDs. The proposed strategy can be a very fast, simple and
      potential tool for the monitoring of diuretics and assaying intestinal
      permeability.

PMID- 20800729
TI  - Determination of cerium ion by polymeric membrane and coated graphite electrode
      based on novel pendant armed macrocycle.
AB  - Plasticized membranes using 2,3,4:12,13,14-dipyridine-1,3,5,8,11,13,15,18
      octaazacycloicosa-2,12-diene (L(1)) and 2,3,4:12,13,14-dipyridine-1,5,8,11,15,18
      hexamethylacrylate-1,3,5,8,11,13,15,18-octaazacycloicosa-2,12-diene (L(2)) have
      been prepared and explored as Ce(III) selective sensors. Effect of various
      plasticizers viz. dibutylphthalate (DBP), tri-n-butylphthalate (TBP), o
      nitrophenyloctylether (o-NPOE), dioctylphthalate (DOP), benzylacetate (BA) and
      anion excluders, sodium tetraphenylborate (NaTPB) and potassium tetrakis p
      (chlorophenyl) borate was studied in detail and improved performance was
      observed. Optimum performance was observed for the membrane sensor having a
      composition of L(2):PVC:o-NPOE:KTpClPB in the ratio of 6:34:58:2 (w/w, mg). The
      performance of the membrane based on L(2) was compared with polymeric membrane
      electrode (PME) as well as with coated graphite electrode (CGE). The electrodes
      exhibit Nernstian slope for Ce(III) ions with limits of detection of 8.3x10(-8)
      mol L(-1) for PME and 7.7x10(-9) mol L(-1) for CGE. The response time for PME and
      CGE was found to be 12 s and 10 s respectively. The potentiometric responses are
      independent of the pH of the test solution in the pH range 3.5-7.5 for PME and
      2.5-8.5 for CGE. The CGE could be used for a period of 5 months. The practical
      utility of the CGE has been demonstrated by its usage as an indicator electrode
      in potentiometric titration of oxalate and fluoride ions with Ce(III) solution.
      The proposed electrode was also successfully applied to the determination of
      fluoride ions in mouthwash solution and oxalate ions in real samples.

PMID- 20800730
TI  - Fabrication and kinetic studies of a novel silver nanoparticles-glucose oxidase
      bioconjugate.
AB  - In this study, a new effective, pH and thermally stable glucose oxidase (GOX)
      silver nanoparticles (AgNPs) bioconjugate was designed. AgNPs were synthesized
      based on the reduction of silver nitrate (AgNO(3)) by sodium borohydride
      (NaBH(4)) using two simple procedures. Periodic acid was used for oxidation of
      the GOX and emission of Lucifer yellow (LyCH) was monitored by spectrofluorometer
      for evaluation of the oxidation properties of the GOX. The oxidized GOX (Ox-GOX)
      was immobilized on AgNPs by its sugar moieties via 6-aminohexanoic acid (6AHA) as
      linker. A sample of the synthesized bioconjugate was loaded on 7.5% non
      denaturing polyacrylamide gel electrophoresis (PAGE) to confirm its structural
      and physical stability. The results from enzymatic activity assay showed that the
      bioconjugate, GOX and Ox-GOX were similar in stability and activity in acidic and
      basic pH (optimum pH=7.0-8.0). Based on the results from thermal stability assay,
      it was found that the activity of the bioconjugate was found to be higher at
      lower temperatures. The V(max) of the bioconjugate, GOX, and Ox-GOX was estimated
      as 28.6, 6.2, and 6 IU microg(-1) enzyme and the K(m) was calculated as 2.7, 9,
      and 9.5 mM, respectively. It was found that the immobilization method improves
      the activity and stability of the GOX in different pH and temperatures. As a
      conclusion, the proposed method opens up the way to the development of a new
      bioconjugate with potential use in sensing, and many find potential applications
      in clinical diagnostics, medicine, and industries.

PMID- 20800732
TI  - Thermal aggregation of bovine serum albumin studied by asymmetrical flow field
      flow fractionation.
AB  - The use of asymmetrical flow field-flow fractionation (AsFlFFF) in the study of
      heat-induced aggregation of proteins is demonstrated with bovine serum albumin
      (BSA) as a model analyte. The hydrodynamic diameter (d(h)), the molar mass of
      heat-induced aggregates, and the radius of gyration (R(g)) were calculated in
      order to get more detailed understanding of the conformational changes of BSA
      upon heating. The hydrodynamic diameter of native BSA at ambient temperature was
      approximately 7 nm. The particle size was relatively stable up to 60 degrees C;
      above 63 degrees C, however, BSA underwent aggregation (growth of hydrodynamic
      diameter). The hydrodynamic diameters of the aggregated particles, heated to 80
      degrees C, ranged from 15 to 149 nm depending on the BSA concentration, duration
      of incubation, and the ionic strength of the solvent. Heating of BSA in the
      presence of sodium dodecyl sulfate (1.7 or 17 mM) did not lead to aggregation.
      The heat-induced aggregates were characterized in terms of their molar mass and
      particle size together with their respective distributions with a hyphenated
      technique consisting of an asymmetrical field-flow fractionation device and a
      multi-angle light scattering detector and a UV-detector. The carrier solution
      comprised 8.5 mM phosphate and 150 mM sodium chloride at pH 7.4. The weight
      average molar mass (M(w)) of native BSA at ambient temperature is 6.6x10(4) g
      mol(-1). Incubation of solutions with BSA concentrations of 1.0 and 2.5 mg mL(-1)
      at 80 degrees C for 1 h resulted in aggregates with M(w) 1.2x10(6) and 1.9x10(6)
      g mol(-1), respectively. The average radius of gyration and the average
      hydrodynamic radius of the heat-induced aggregate samples were calculated and
      compared to the values obtained from the size distributions measured by AsFlFFF.
      For comparison static light scattering measurements were carried out and the
      corresponding average molar mass distributions of solutions with BSA
      concentrations of 1.0 and 2.5 mg mL(-1) at 80 degrees C for 1 h gave aggregates
      with M(w) 1.7x10(6) and 3.5x10(6) g mol(-1), respectively.

PMID- 20800731
TI  - Towards the development of a portable sensor based on a molecularly imprinted
      membrane for the rapid determination of salbutamol in pig urine.
AB  - A new type of conductometric probe based on a molecularly imprinted membrane
      (MIM) for the detection of salbutamol has been designed and fabricated. The probe
      consists of two parallel screen-printed electrodes (SPE). One of the SPEs was
      coated with a molecularly imprinted membrane using salbutamol as the template,
      and the other was modified with a non-molecularly imprinted membrane (N-MIM).
      Measurements of salbutamol were conducted after the conductometric probe had been
      connected to a commercial portable conductometer. Multi-sample or successive
      detections could be easily accomplished by replacing the one-off SPE coated with
      the salbutamol molecularly imprinted membrane with a new one. The conductometric
      response of the sensor to the concentration of salbutamol displayed a linear
      correlation over a range from 50 to 280 nM, with a detection limit of 13.5 nM.
      The recoveries reached 92.1-98.3% based on pig urine samples. In addition, the
      sensor based on this new type of probe demonstrated high sensitivity and
      selectivity for salbutamol.

PMID- 20800734
TI  - Single-walled carbon nanotubes as stationary phase in gas chromatographic
      separation and determination of argon, carbon dioxide and hydrogen.
AB  - A chromatographic technique is introduced based on single-walled carbon nanotubes
      (SWCNTs) as stationary phase for separation of Ar, CO(2) and H(2) at parts per
      million (ppm) levels. The efficiency of SWCNTs was compared with solid materials
      such as molecular sieve, charcoal, multi-walled carbon nanotubes and carbon
      nanofibers. The morphology of SWCNTs was optimized for maximum adsorption of
      H(2), CO(2) and Ar and minimum adsorption of gases such as N(2), O(2), CO and
      H(2)O vapour. To control temperature of the gas chromatography column, peltier
      cooler was used. Mixtures of Ar, CO(2) and H(2) were separated according to
      column temperature program. Relative standard deviation for nine replicate
      analyses of 0.2 mL H(2) containing 10 microL of each Ar or CO(2) was 2.5% for Ar,
      2.8% for CO(2) and 3.6% for H(2). The interfering effects of CO, and O(2) were
      investigated. Working ranges were evaluated as 40-600 ppm for Ar, 30-850 ppm for
      CO(2) and 10-1200 ppm for H(2). Significant sensitivity, small relative standard
      deviation (RSD) and acceptable limit of detection (LOD) were obtained for each
      analyte, showing capability of SWCNTs for gas separation and determination
      processes. Finally, the method was used to evaluate the contents of CO(2) in air
      sample.

PMID- 20800733
TI  - Rapid resolution liquid chromatography-mass spectrometry and high-performance
      liquid chromatography-fluorescence detection for metabolism and pharmacokinetic
      studies of ergosta-4,6,8(14),22-tetraen-3-one.
AB  - Ergosta-4,6,8(14),22-tetraen-3-one (ergone) from many medicinal plants has been
      demonstrated to possess a variety of pharmacological activities in vivo and in
      vitro, including cytotoxic, diuretic and immunosuppressive activity. Metabolism
      and pharmacokinetic studies on rat were conducted for ergone. Rapid resolution
      liquid chromatography with atmospheric pressure chemical ionization tandem multi
      stage mass spectrometry (RRLC-APCI-MS(n)) and high-performance liquid
      chromatography with fluorescence detection (HPLC-FLD) methods were applied for
      the identification and quantification of ergone and its metabolite from rat
      plasma, faeces and urine. A metabolite was identified by RRLC-DAD-APCI-MS(n):
      22,23-epoxy-ergosta-4,6,8(14)-triaen-3-one (epoxyergone). The concentrations of
      the analyte with its metabolites were determined by HPLC-FLD at excitation
      wavelength of 370 nm and emission wavelength of 485 nm. The samples were
      deproteinized with methanol after addition of camptothecin as internal standard
      (IS). The analysis was performed on a Diamonsil C18 column (150 mm x 4.6 mm x 5
      microm) with a mobile phase gradient consisting of methanol and water at a flow
      rate of 1 mL min(-1). The assay was linear over the concentration range of 42
      1500, 36-7500 and 42-1500 ng mL(-1) for plasma, faecal homogenate and urine
      respectively. The absolute recoveries were found to be 97.0+/-1.2%, 98.1+/-0.7%
      and 96.6+/-1.8% for plasma, faecal homogenate and urine respectively. The intra
      day and inter-day relative standard deviations (RSD) were less than 10%. The
      previous HPLC-MS/MS method is not affordable for most laboratories because of the
      specialty requirement and high equipment cost. However, the HPLC-FLD method is
      economic and operating simply for quantitative determination of ergone and its
      metabolite in rat plasma, faeces and urine. In addition, liquid chromatography
      coupled with ion trap multi-stage mass spectrometry is becoming a useful
      technique for ergone metabolite identification.

PMID- 20800735
TI  - Electrodeposition of PANi films on platinum needle type microelectrodes.
      Application to the oxidation of ascorbate in human plasma.
AB  - Needle type (165 microm(2)) and small Pt disc (3-11 microm(2)) microelectrodes
      were used for the electrodeposition of composite poly(aniline), PANi, films by
      cyclic voltammetry and chronoamperometry for the oxidation of ascorbate. PANi
      electroactivity at neutral pH was retained through polymer alkylation or by using
      large poly-anions, such as poly(vinylsulfonate), PVS, and poly(styrenesulfonate),
      PSS. Hence the growth of the composite films was studied in the presence of
      different counter ions such as SO(4)(2-), Cl(-), NaPVS and NaPSS. The morphology
      of the resulting films was examined by scanning electron microscopy. Results
      showed that flat PANi films with thicknesses much lower than the microelectrode
      radius were obtained by potentiodynamic electrodeposition. On the other hand
      films with mushroom shapes, with significant spill over, were obtained under
      constant potential. The resulting polymer modified microelectrodes films were
      shown to be suitable for the oxidation of ascorbate at 0.1 V vs. SCE and pH 7
      with a detection limit of 1 microM for PANi/PSS composites. The current was
      independent of film thickness, mass transport controlled at low ascorbate
      concentrations and not affected by the presence of common interferences such as
      uric acid, glutathione or vitamin E. Due to their excellent properties the PANi
      PSS film coated microelectrodes were used for the amperometric detection of
      ascorbate in human plasma. The results are encouraging for the use of small
      polymer modified Pt needle type microelectrodes for the detection of ascorbate in
      biological systems.

PMID- 20800736
TI  - Characterization of metal-humic acid complexes by polyacrylamide gel
      electrophoresis-laser ablation-inductively coupled plasma mass spectrometry.
AB  - A new speciation methodology based on the use of 1D-PAGE (one dimensional
      polyacrylamide gel electrophoresis), IEF (isoelectric focusing electrophoresis)
      and 2D-PAGE (two dimensional-polyacrylamide gel electrophoresis) as separation
      techniques and LA-ICP-MS (laser ablation-inductively coupled plasma mass
      spectrometry) as detection system have been applied to study the distribution of
      metal-humic acids (metal-HA) complexes in environmental samples. The use of 1D
      Tris borate method using low current (10 mA) and Tris borate as trailing ion
      previous to LA-ICP-MS measurements, allowed to obtain the distribution of metals
      HA complexes from a compost sample maintaining metals-HA complexes stability. It
      was observed that metals were associated with the smallest HA size fraction
      (around 3 kDa), validating results obtained by high performance size-exclusion
      chromatography (HP-SEC), cross-flow field flow fractionation (FIFFF) and
      ultrafiltration. IEF-LA-ICP-MS profiles indicated that there are two main
      regions: (A) with 3<pI<4.5 and (B) with pI>5. The biggest metals-HA signals are
      obtained in A region (low pIs) corresponding to low molecular weight (MW)
      compounds which are predominant in our compost sample indicating a low
      stabilization of organic matter is low. These results are coincident with 1D-Tris
      borate PAGE-LA-ICP-MS results. The use of 2D-PAGE method followed by LA-ICP-MS
      confirmed the results obtained by 1D and IEF as PAGE methods and added
      information about humic acid molecular size distribution.

PMID- 20800737
TI  - Modern sampling and analytical methods for the determination of trace elements in
      marine particulate material using magnetic sector inductively coupled plasma-mass
      spectrometry.
AB  - Trace elements often limit phytoplankton growth in the ocean, and the
      quantification of particulate forms is essential to fully understand their
      biogeochemical cycling. There is presently a lack of reliable measurements on the
      trace elemental content of marine particles, in part due to the inadequacies of
      the sampling and analytical methods employed. Here we report on the development
      of a series of state-of-the-art trace metal clean methods to collect and process
      oceanic particulate material in open-ocean and sea ice environments, including
      sampling, size-fractionated filtration, particle digestions and analysis by
      magnetic sector inductively coupled plasma-mass spectrometry (ICP-MS). Particular
      attention was paid to the analysis of certified reference materials (CRMs) and
      field blanks, which are typically the limiting factor for the accurate analysis
      of low concentrations of trace metals in marine particulate samples. Theoretical
      detection limits (3 s of the blank) were low for all 17 elements considered, and
      varied according to filter material and porosity (sub-microg L(-1) for
      polycarbonate filters and 1-2 microg L(-1) for quartz and polyester filters).
      Analytical accuracy was verified using fresh water CRMs, with excellent
      recoveries noted (93-103%). Digestion efficiencies for various acid combinations
      were assessed using sediment and plankton CRMs. Using nitric acid only, good
      recoveries (79-90%) were achieved for Mo, Cd, Ba, Pb, Mn, Fe, Co, Ni, Cu, Zn and
      Ga. The addition of HF was necessary for the quantitative recovery of the more
      refractory trace elements such as U, Al, V and Cr. Bioactive elements such as P
      can also be analysed and used as a biomass normaliser. Our developed sampling and
      analytical methods proved reliable when applied during two major field programs
      in both the open Southern Ocean and Antarctic sea ice environments during the
      International Polar Year in 2007. Trace elemental data are presented for
      particulate samples collected in both suspended and sinking marine material, and
      also within sea ice cores.

PMID- 20800738
TI  - Determination of sulphate in water and biodiesel samples by a sequential
      injection analysis--multivariate curve resolution method.
AB  - A spectrophotometric sequential injection analysis (SIA-DAD) method linked to
      multivariate curve resolution-alternating least squares (MCR-ALS) has been
      developed for sulphate determination. This method involves the reaction, inside
      the tubes of the SIA system, of sulphate with barium-dimethylsulphonazo (III)
      complex, Ba-DMSA (III), displacing Ba(2+) from the complex and forming DMSA
      (III). When the reaction products reach the detector a data matrix is obtained,
      which allows a second-order calibration to be developed. The experimental
      conditions (concentration and sample and reagent volumes) to obtain the highest
      sensitivity have been chosen applying a 2(4-1) fractional factorial design. The
      proposed sequential flow procedure permits up to 15 mg SO(4)(2-) L(-1) to be
      determined with a limit of detection of 1.42 mg L(-1) and it is able to monitor
      sulphate in samples at a frequency of 15 samples per hour. The method was applied
      to determine sulphate in natural and residual waters and in biodiesel. The
      reliability of the method was established for water samples by parallel
      determination using a standard turbidimetric method for sulphate in natural and
      residual water samples with results within statistical variation. For biodiesel
      samples, the method was validated comparing the concentration of some spiked
      samples with the expected concentration using a test-t.

PMID- 20800739
TI  - Towards a robust water content determination of freeze-dried samples by near
      infrared spectroscopy.
AB  - The possibility for determination of the water content in pharmaceutical samples
      by near-infrared (NIR) spectroscopy has been more widely investigated in the past
      few years. However, many studies claim that changes in sample composition will
      require the establishment of a new method. The aim of this study was several
      fold: firstly to investigate validation aspects of water content determination in
      samples with varying composition and furthermore to see if a model based solely
      on freeze-dried mannitol-sucrose mixtures can be established that will be able to
      predict water contents for samples containing proteins, excipients or having a
      lower density of freeze-dried solids. Samples were measured by NIR, standard
      normal variate (SNV) corrected and the obtained spectra were compared with the
      results from a conventional Karl-Fischer titration by means of multivariate
      analysis, namely principal component analysis (PCA) and partial least square
      regression (PLS). For the overall sample set, a highly linear correlation between
      the NIR and the Karl-Fischer method with a slope of 1.00, an R(2) value of 0.98
      and a root mean square error of cross-validation (RMSECV) of 0.15% were found. In
      a second step samples solely consisting of mannitol and sucrose mixtures were
      used to build a calibration set, which resulted in a RMSECV of 0.16%. The
      prediction of the remaining samples, which included protein or excipient
      containing samples, as well as lower density samples, resulted in a root mean
      square error of prediction (RMSEP) of 0.19%. Thus the present study demonstrated,
      that a general model for the determination of the water content by NIR could be
      established, within the limits investigated.

PMID- 20800740
TI  - Highly sensitive electrochemiluminescence displacement method for the study of
      DNA/small molecule binding interactions.
AB  - Non-covalent binding interactions of small molecules with DNA play important
      roles in regulating gene expression and gene function. In this work, a highly
      sensitive electrochemiluminescence (ECL) displacement method has been developed
      to investigate such interactions, particularly for weak DNA binders. This ECL
      method relies on a double-stranded DNA film deposited on an indium tin oxide
      electrode (ITO) surface by layer-by-layer self-assembly. A DNA intercalator,
      [Ru(bpy)(2)(dppz)](2+) (bpy = 2,2'-bipyridine, dppz = dipyrido[3,2-a:2'3'
      c]phenazine), is employed as the ECL signal indicator. If a test compound
      competes with the indicator for the same binding sites in DNA, it would displace
      the indicator from the film and reduce ECL signal. The new method was validated
      by measuring five well-known DNA-binding organic molecules including quinacrine,
      H33258, thiazole orange, ethidium bromide and 4,6-diamidine-2-phenylindole
      dihydrochloride. Due to high ECL sensitivity, only 0.4 micromol L(-1)
      [Ru(bpy)(2)(dppz)](2+) was needed in the ECL displacement measurement, which is
      about 75-fold less than the concentration in the voltammetric measurement. The
      lowered concentration permitted direct measurement of IC(50) values of eight
      hydroxylated polycyclic aromatic hydrocarbons in their ECL displacement curves
      and subsequent calculation of their binding constants with DNA. The ECL
      displacement method is particularly useful for investigating weak DNA binders
      with limited aqueous solubility.

PMID- 20800741
TI  - Quantitative analysis of heavy metals in automotive brake linings: a comparison
      between wet-chemistry based analysis and in-situ screening with a handheld X-ray
      fluorescence spectrometer.
AB  - Two extraction procedures for ecologically relevant elements present in
      automotive brake linings (Sb, Bi, Pb, Cd, Cr (total), Co, Cu, Mo, Ni, Sr, V, Zn,
      Sn) were developed and validated, applying a high pressure asher (HPA-S) and
      microwave extraction, respectively. Both of these methods allowed for the
      quantitative analysis of the extracted elements by inductively coupled plasma
      optical emission spectrometry (ICP-OES). The results were compared to
      measurements using a handheld energy-dispersive X-ray fluorescence spectrometer
      (ED-XRF), being in discussion by regulating agencies as in-situ screening tool
      for brake pads. The comparison indicates that the handheld ED-XRF analysis is
      basically an efficient screening tool for a reliable assessment of trace metal
      contents in automotive brake pads with respect to legal standards. While a
      quantitative determination of elements like Cd, Co, Cr, Mn, Mo, Ni, Pb and Sb was
      achievable, other elements (V, Cu, Bi, Zn, Sn and Sr) could only be determined
      qualitatively due to the special matrix characteristics of brake pads.

PMID- 20800742
TI  - Determination of volatile monophenols in beer using acetylation and headspace
      solid-phase microextraction in combination with gas chromatography and mass
      spectrometry.
AB  - Monophenols are widely spread compounds contributing to the flavour of many foods
      and beverages. They are most likely present in beer, but so far, little is known
      about their influence on beer flavour. To quantify these monophenols in beer, we
      optimised a headspace solid-phase microextraction method coupled to gas
      chromatography-mass spectrometry. To improve their isolation from the beer matrix
      and their chromatographic properties, the monophenols were acetylated using
      acetic anhydride and KHCO(3) as derivatising agent and base catalyst,
      respectively. Derivatisation conditions were optimised with attention for the pH
      of the reaction medium. Additionally, different parameters affecting extraction
      efficiency were optimised, including fibre coating, extraction time and
      temperature and salt addition. Afterwards, we calibrated and validated the method
      successfully and applied it for the analysis of monophenols in beer samples.

PMID- 20800743
TI  - Accessibility governs the relative reactivity of basic residues in formaldehyde
      induced protein modifications.
AB  - Cross-linking of proteins in a complex requires the chemical modification of the
      proteins in order to form a covalent link. This can be achieved in vivo using
      formaldehyde as it is small and rapidly permeates the cell membrane. Previous
      model studies of the speed and specificity of the first step of this reaction on
      peptides have suggested that residue accessibility and sequence micro-environment
      play a significant role in the production of the reactive intermediate necessary
      for cross-linking. This dependency was therefore further investigated on model
      proteins, which contain a more complex tertiary structure. Under mild reaction
      conditions, similar to those used for in vivo protein cross-linking, it was found
      that the vast majority of modification occurred on lysines, tertiary structure
      and solvent accessible surface area played a major role in regulating the extent
      of formaldehyde-induced modifications, and that the modifications on a folded
      protein did not significantly affect its tertiary structural stability.

PMID- 20800745
TI  - Laser-induced thermal effect in surface plasmon resonance.
AB  - In this work, thermal effect inherent in long-term irradiation of a focused laser
      beam may become a major source of error in surface plasmon resonance (SPR)
      measurements, especially when infinitesimal signals (e.g., reorganization of
      monolayers or conformational changes of immobilized proteins) are measured. The
      laser-induced thermal effect was examined by continuously monitoring changes
      brought about by injecting 2% ethanol solution into a flow cell housing bare and
      chemically modified gold films that had been irradiated by a laser beam for
      various times, and a maximum relative error of 21% was obtained. Factors
      affecting the SPR response, namely solution flow rate, compactness of the
      adsorbate layer, and power of the laser beam, were examined. The SPR dip shift
      (SPR angular shift) was shown to be dependent not only on the magnitude of the
      laser power but also on the thermal dissipation at the metal-solution interface.
      With a better understanding of the parameters affecting the thermal energy
      dissipation and the temperature dependence of the SPR signals, measures can be
      taken to improve the accuracy of SPR data. We show as an example that, if the
      laser-induced thermal effect is not considered or reduced, accuracy in
      determining redox-triggered reorganization of a pre-immobilized 11
      ferrocenylundecanethiol self-assembled monolayer (SAM) may be decreased by more
      than 40%, leading to an erroneous conclusion.

PMID- 20800744
TI  - Nanoengineered optical urea biosensor for estimating hemodialysis parameters in
      spent dialysate.
AB  - An optical biosensing scheme based on urease encapsulated calcium alginate
      microspheres which are coated with polyelectrolyte nanofilms predominantly
      composed of cresol red (CR) dye is demonstrated in this paper. The dye molecules
      within the nanofilms are deposited via the layer-by-layer (LbL) self-assembly
      technique on the microspheres and used as the optical transducer. A flow through
      cell constructed using a cuvette attached to a fiber optic spectrometer was used
      to determine the response of the biosensor to standard urea solutions of
      different concentrations. The change in pH and the absorbance ratio was monitored
      with time and these results were used for measurements of urea concentrations in
      the spent dialysate fluid. The biological parameters controlling hemodialysis
      such as dialyzer clearance or Kt/V and percent removed urea (PRU) have also been
      reported. The results demonstrate that the urea biosensor is pH reversible with a
      sensitivity of 0.09 pH units/min and is able to detect a change of 0.005 ratio
      units in urea concentration ranging 0.1-60 mg dL(-1). The response time of the
      sensor was calculated as 8 min while the detection range of urea covered the
      levels that are present in the spent dialysate fluid. The results obtained in the
      analysis of biological samples were in good agreement with those obtained by a
      reference method, showing no significant differences at a confidence level of
      95%.

PMID- 20800746
TI  - Detection of copper ions using microcantilever immunosensors and enzyme-linked
      immunosorbent assay.
AB  - A sensitive and specific monoclonal antibody (designated as mAb6A9) recognizing a
      Cu(II)-ethylenediamine-N,N,N',N'-tetraacetic acid (EDTA) complex but not metal
      free EDTA was obtained by using an 1-(4-aminobenzyl)-EDTA-Cu(II) complex
      covalently coupled to a carrier protein as an immunogen to immunize the Balb/c
      mice. A mAb6A9-modified microcantilever sensor (MCS) was developed. A bending
      response was found to occur at or below 1 ng mL(-1) of Cu(II)-EDTA complex. An
      indirect competitive enzyme-linked immunosorbent assay (icELISA) was developed
      with mAb6A9. The icELISA had a half maximum inhibition concentration and working
      range of approximately 1.8 and 0.2-17 ng mL(-1), respectively. The icELISA showed
      cross-reactivity of 18.8%, 1.1% and less than 1% with bivalent cobalt, mercury
      and other metals, respectively. The icELISA and functionalized MCSs were utilized
      to analyze the content of copper in spiked tap water samples. The assay
      conditions were optimized. The results of icELISA and MCS correlated well with
      those obtained by graphite furnace atomic absorption spectrometry.

PMID- 20800747
TI  - Fluoroimmunoassay based on suppression of fluorescence self-quenching for ultra
      sensitive detection of herbicide diuron.
AB  - A highly sensitive heterogeneous fluoroimmunoassay has been developed for
      monitoring phenylurea herbicide diuron on the basis of suppression of
      fluorescence self-quenching. Specific antibody against diuron was produced and
      labeled with rhodamine isothiocyanate at different molar ratios and used as
      tracer in the developed immunoassay. The analytical sensitivity of immunoassay
      was enhanced by changing the microenvironment of fluorescence label with glycerin
      solution after the completion of immunoassay. Enhancer treatment on developed
      immunoassay showed improvement of fluorescence signal intensity by approximately
      4-folds with higher stability compared with the signal determined without
      enhancer treatment of the wells. The immunoassay has a detection limit of 0.1 ng
      mL(-1) with good signal precision (approximately 2%) in the optimum working
      concentration range between 0.01 and 100 ng mL(-1) of diuron. In addition, the
      use of enhancer improved the stability of fluorescence signal by suppression of
      self-quenching of fluorescence signal. The proposed method has been applied
      satisfactorily for the ultra-sensitive detection of herbicide diuron in samples.

PMID- 20800748
TI  - Effective desorption of tritium from diverse solid matrices and its application
      to routine analysis of decommissioning materials.
AB  - Tritium extraction from materials is most commonly carried out using oxidative
      thermal desorption in purpose-built furnace systems and typically involves
      trapping the product in a water bubbler which is sampled for measurement using
      liquid scintillation counting (LSC). The performance of perhaps the most widely
      used commercial system, the Raddec Pyrolyser, has been evaluated for a broad
      range of sample types. Several parameters that were expected to affect tritium
      desorption and recovery were systematically studied. These included sample
      heating rates and end-point temperatures, carrier/oxidant gas flows, catalyst
      temperature, bubbler trapping and carry-over/memory effects. A catalyst such as
      platinised-alumina is used to ensure the quantitative oxidation of volatile
      combustion products to HTO and CO(2). This also ensures that the trapped
      decomposition products do not colourise the bubbler solutions that are
      subsequently sampled for LSC. Tritium evolution profiles were determined for a
      range of sample types and were obtained by systematically changing bubblers at a
      set of progressively increasing temperatures. These experiments showed the
      maximum heating temperature and total combustion time required for the complete
      recovery of tritium from samples was dependent on the sample matrix types and the
      (3)H form. These evolution profiles need only be determined once and are readily
      transferable to other Pyrolyser systems. For example tritiated water is rapidly
      liberated from samples at temperature around 100 degrees C whereas (3)H
      substituted for structural H in organic species can require a temperature in
      excess of 300 degrees C to be released. Higher temperatures (up to 900 degrees C)
      are needed to liberate (3)H originating from neutron capture reactions on trace
      Li or B within a material (e.g. reactor graphite or concrete). The furnace system
      investigated is highly effective at extracting tritium and (14)C from all sample
      types studied (soil, sediment, biota, wood, metal, plastic, concrete, graphite,
      etc.) and overall it demonstrates high and reproducible recoveries.

PMID- 20800749
TI  - Poly(methacrylic acid-co-ethylene glycol dimethacrylate) monolith microextraction
      coupled with high performance liquid chromatography for the determination of
      phthalate esters in cosmetics.
AB  - A simple, sensitive, and rapid strategy has been reported in this work which is
      based on polymer monolith microextraction (PMME) and high performance liquid
      chromatography (HPLC) for the determination of phthalate esters in cosmetics. A
      poly(methacrylic acid-co-ethylene glycol dimethacrylate) (MAA-EGDMA) monolithic
      capillary column is selected as the extraction medium for PMME. In order to
      obtain optimum extraction efficiency, the conditions of PMME including sample
      flow rate, sample volume, sample pH, and eluent flow rate have been investigated.
      Under the optimum conditions, the limits of detection for dimethyl phthalate
      (DMP), di-n-butyl phthalate (DBP), dicyclohexyl phthalate (DCHP), and di-n-octyl
      phthalate (DOP) based three times of standard deviations of blank by seven
      replicated are in the range of 0.7-3.7 ng mL(-1). The reproducibility of the
      method is obtained with intra-day and inter-day relative standard deviations less
      than 3.2% and 7.7%, respectively. The method has been successfully applied to the
      determination of the four phthalate esters in cosmetics with a recovery range of
      81.2-108.8% in all the samples.

PMID- 20800750
TI  - The relationship between obsessive beliefs and symptom dimensions in obsessive
      compulsive disorder.
AB  - Research findings on the specific relationships between beliefs and OCD symptoms
      have been inconsistent, yet the existing studies vary in their approach to
      measuring the highly heterogeneous symptoms of this disorder. The Dimensional
      Obsessive-Compulsive Scale (DOCS) is a new measure that allows for the assessment
      of OCD symptom dimensions, rather than types of obsessions and compulsions per
      se. The present study examined the relationship between OCD symptom dimensions
      and dysfunctional (obsessive) beliefs believed to underlie these symptom
      dimensions using a large clinical sample of treatment-seeking adults with OCD.
      Results revealed that certain obsessive beliefs predicted certain OCD symptom
      dimensions in a manner consistent with cognitive-behavioral conceptual models.
      Specifically, contamination symptoms were predicted by responsibility/threat
      estimation beliefs, symmetry symptoms were predicted by perfectionism/certainty
      beliefs, unacceptable thoughts were predicted by importance/control of thoughts
      beliefs and symptoms related to being responsible for harm were predicted by
      responsibility/threat estimation beliefs. Implications for cognitive
      conceptualizations of OCD symptom dimensions are discussed.

PMID- 20800751
TI  - Constructing a self: the role of self-structure and self-certainty in social
      anxiety.
AB  - Current cognitive models stress the importance of negative self-perceptions in
      maintaining social anxiety, but focus predominantly on content rather than
      structure. Two studies examine the role of self-structure (self-organisation,
      self-complexity, and self-concept clarity) in social anxiety. In study one, self
      organisation and self-concept clarity were correlated with social anxiety, and a
      step-wise multiple regression showed that after controlling for depression and
      self-esteem, which explained 35% of the variance in social anxiety scores, self
      concept clarity uniquely predicted social anxiety and accounted for an additional
      7% of the variance in social anxiety scores in an undergraduate sample (N=95) and
      the interaction between self-concept clarity and compartmentalisation (an aspect
      of evaluative self-organisation) at step 3 of the multiple regression accounted
      for a further 3% of the variance in social anxiety scores. In study two, high
      (n=26) socially anxious participants demonstrated less self-concept clarity than
      low socially anxious participants (n=26) on both self-report (used in study one)
      and on computerised measures of self-consistency and confidence in self-related
      judgments. The high socially anxious group had more compartmentalised self
      organisation than the low anxious group, but there were no differences between
      the two groups on any of the other measures of self-organisation. Self-complexity
      did not contribute to social anxiety in either study, although this may have been
      due to the absence of a stressor. Overall, the results suggest that self
      structure has a potentially important role in understanding social anxiety and
      that self-concept clarity and other aspects of self-structure such as
      compartmentalisation interact with each other and could be potential maintaining
      factors in social anxiety. Cognitive therapy for social phobia might influence
      self-structure, and understanding the role of structural variables in maintenance
      and treatment could eventually help to improve treatment outcome.

PMID- 20800754
TI  - Approach to anemia.

PMID- 20800755
TI  - Anemia in the elderly.

PMID- 20800756
TI  - Myelodysplastic syndromes: what a primary care physician needs to know.

PMID- 20800757
TI  - Heterologous protein secretion by bacillus species from the cradle to the grave.
AB  - The Gram-positive bacterium Bacillus subtilis and some of its close relatives are
      widely used for the industrial production of enzymes for the detergents, food,
      and beverage industries. The choice of these organisms is based almost
      exclusively on the high capacity of their secretion systems that are, under the
      right conditions, able to secrete proteins at grams per liter concentrations. In
      contrast, there are relatively few examples of Bacillus species being used for
      the cytoplasmic production of proteins. The range of proteins that are capable of
      high-level production and secretion is limited by a combination of
      characteristics of both the target protein and the host bacterium. The secretion
      pathway includes checkpoints that are designed to validate the authenticity of
      pathway substrates. Although many of these checkpoints are known, only some can
      be overcome by reengineering the host. As a result, the yield of heterologous
      protein production is extremely variable. In this review, we consider the
      Bacillus protein secretion pathway from the synthesis of the target protein
      (cradle) to its emergence at the outer surface of the complex cell wall (grave),
      and discuss the roles of the various checkpoints both with respect to the target
      protein and their role on cell homeostasis.

PMID- 20800758
TI  - Function of protein phosphatase-1, Glc7, in Saccharomyces cerevisiae.
AB  - Budding yeast, Saccharomyces cerevisiae, and its close relatives are unique among
      eukaryotes in having a single gene, GLC7, encoding protein phosphatase-1 (PP1).
      This enzyme with a highly conserved amino acid sequence controls many processes
      in all eukaryotic cells. Therefore, the study of Glc7 function offers a unique
      opportunity to gain a comprehensive understanding of this critical regulatory
      enzyme. This review summarizes our current knowledge of how Glc7 function
      modulates processes in the cytoplasm and nucleus. Additionally, global Glc7
      regulation is described.

PMID- 20800759
TI  - Milliliter-scale stirred tank reactors for the cultivation of microorganisms.
AB  - This review focuses on recent developments in the field of miniaturized stirred
      tank bioreactors for application in high-throughput bioprocess development.
      Different reactor concepts and their potential for parallel bioprocess
      development are discussed. A detailed description of important engineering state
      variables, their measurement at small-scale and their implication for scale-up
      and scale-down of bioprocesses are given. Examples of two different parallel
      cultivations at small-scale are presented: one with Escherichia coli and the
      other one with the filamentous microorganism Streptomyces tendae. It is shown
      that results obtained in parallelized milliliter-scale stirred tank reactors can
      be scaled up to the laboratory- and/or pilot-scale in a highly reliable manner.
      This helps to reduce development times for bioprocesses significantly. Finally,
      directions for future research are presented.

PMID- 20800760
TI  - Type I interferon modulates the battle of host immune system against viruses.
AB  - Type I interferon (IFN), as its name implies, 'interferes' with virus replication
      by activating numerous genes. Further, virus-induced type I IFN regulates the
      magnitude and functions of cells directing the host immune system. Importantly,
      recent exploration into how type I IFN operates following virus infection has
      advanced our understanding of its role with respect to modulation of host innate
      and adaptive immune responses. Such activities include the activation of antigen
      presenting dendritic cells and the localization, expansion or differentiation of
      virus-specific T lymphocytes and antibody-producing B lymphocytes. However, type
      I IFN not only benefits the host but can also induce unnecessary or extremely
      pathogenic immune responses. This review focuses on such interactions and the
      manner in which type I IFN induces dynamic changes in the host immune network,
      particularly adaptive immune responses to viral invasion. Manipulating the type I
      IFN-mediated host immune response during virus infections could provide new
      immunotherapeutic interventions to remedy viral diseases and implement more
      effective and sustainable type I IFN therapy.

PMID- 20800761
TI  - A comparative study of European rare disease and orphan drug markets.
AB  - OBJECTIVES: This article aims to compare regulatory aspects of rare disease and
      orphan drug markets in Belgium, France, Italy, the Netherlands, Sweden and the
      United Kingdom. METHODS: Information was derived from the international
      literature, analysis of legal texts, and a survey completed by national experts.
      RESULTS: These countries adopted varying approaches towards regulating rare
      disease and orphan drug markets and, hence, the availability, pricing and
      reimbursement of orphan drugs vary between countries. Strategies to keep down
      prices include public procurement in Sweden, profit controls in the United
      Kingdom, and price comparisons with other countries. To gain reimbursement, the
      cost-effectiveness and/or budget impact of orphan drugs is considered in some
      countries. Other societal considerations, such as whether the drug treats a life
      threatening disease, are sometimes taken into account. CONCLUSIONS: Extensive
      government intervention exists in rare disease and orphan drug markets in the
      countries studied. Our recommendations are to define priorities for research on
      rare diseases and orphan drugs at the European level, to set up disease and
      patient registries with a view to investigating the long-term effectiveness and
      cost-effectiveness of orphan drugs, to assess the profitability of orphan drugs,
      and to take into account societal considerations when evaluating orphan drugs.

PMID- 20800762
TI  - Using micro-simulation to create a synthesised data set and test policy options:
      the case of health service effects under demographic ageing.
AB  - OBJECTIVES: To assess micro-simulation for testing policy options under
      demographic ageing. METHODS: Individual-level data were drawn from the New
      Zealand Health Survey (1996/7 and 2002/3), a national survey of ambulatory care
      in New Zealand (2001/2), and the Australian National Health Survey (1995). Health
      service effects assessed were visits to the family doctor, and rates of
      prescribing and referral. We created a representative set of synthetic health
      histories by imputation and tested the health service effects of different policy
      scenarios. These were created by varying ageing and morbidity trajectories,
      degree of social support available, and intensity of practitioner behaviour.
      RESULTS: The set of synthetic health histories created by combining the data
      sources generated outcomes reasonably close to external benchmarks. Altering the
      age distribution of 2002 to approximate settings for 2021 produced no change in
      rates of visiting, prescribing, or referral for the 65-and-over population.
      Quantifying the health service effects of different scenarios showed no impact on
      visit rates by varying social support, but substantial differences for visits
      between high and low morbidity scenarios and for prescribing and referral rates
      according to practitioner behaviour. CONCLUSIONS: There is potential for micro
      simulation to assist in the synthesis of data and to help quantify scenario
      options for policy development.

PMID- 20800763
TI  - Special issue on estrogen actions in the brain.

PMID- 20800764
TI  - The underappreciated impact of heart disease.
AB  - The 2009 recommendations of the U.S. Preventive Services Task Force regarding
      mammography have called attention to the roles of prevention and screening in
      promoting women's health. We take this opportunity to raise awareness of another
      devastating illness in women, ischemic heart disease, and to suggest that
      screening for ischemic heart disease, by providing early detection and
      identifying women who would benefit most from intensified medical therapy, merits
      consideration.

PMID- 20800765
TI  - Pregnancy: a screening test for later life cardiovascular disease.

PMID- 20800766
TI  - Gender differences in psychosocial issues affecting low-income, underserved
      patients' ability to manage cardiovascular disease.
AB  - RESEARCH OBJECTIVE: This paper examines the psychosocial challenges that
      interfere with low-income, underserved patients' ability to manage cardiovascular
      disease (CVD) and seeks to explore the differences in how men and women manifest
      these issues. STUDY DESIGN: We convened 33 focus group discussions with low
      income, underserved heart patients in 10 U.S. communities. Using content
      analysis, we identified key psychosocial issues that illustrate the psychosocial
      barriers patients experience as they manage their illness and analyzed these
      issues by gender to uncover differences in coping and self-management. PRINCIPAL
      FINDINGS: We identified eight factors that represent the most frequently cited
      psychosocial issues by participants: 1) depression; 2) fear; 3) anger; 4) disease
      stress; 5) financial stress; 6) social isolation; 7) burden to family and
      friends; and 8) social supports. For the most part, men and women characterized
      psychosocial problems very differently. Among the eight themes identified, four
      emerged as dominant themes among women participants and three emerged among male
      participants. One factor, depression, was a prevalent theme for both men and
      women. CONCLUSION: This study suggests that low-income, underserved women and men
      experience gender-specific psychosocial problems that interfere with their
      ability to manage their disease. Programs and interventions to improve the
      psychosocial issues related to CVD, particularly for low-income underserved
      populations, may be more effective if they are designed to address the unique
      ways in which women and men experience their illnesses.

PMID- 20800767
TI  - Self-reported delays in receipt of health care among women with diabetes and
      cardiovascular conditions.
AB  - PURPOSE: Midlife and older adults have high rates of chronic conditions, and
      differences in health insurance coverage may affect their access to care. Women
      may be particularly at risk for access problems. This study examines the
      association of gender and health insurance status with delays in care, a
      dimension of access to care, among midlife (age 45-64) and older (age > or = 65)
      adults with diabetes and cardiovascular conditions. METHODS: Data were from the
      2004 through 2006 national Medical Expenditure Panel Survey. A total of 4,706
      adults with self-identified diabetes and 17,636 adults with self-identified
      cardiovascular conditions, aged 45 years and older, were included. The analyses
      examined associations of gender and insurance status with self-reported delays in
      medical care, dental care, prescription medication, and illness/injury care,
      using bivariate and multivariate analyses adjusted for race/ethnicity, education,
      income, and perceived health status. MAIN FINDINGS: Midlife women with diabetes
      or cardiovascular conditions were more likely to report delays in care than men,
      even after adjusting for key factors (85%-111% higher odds of delays among
      diabetes patients, 56%-84% higher odds of delays among cardiovascular patients;
      all p < .01). Many, but not all, of these gender differences were eliminated
      among Medicare-insured older adults. Among midlife adults, health insurance
      coverage differences were also significantly associated with delays in care.
      CONCLUSION: Women are more likely to experience delays in health care, even after
      adjusting for health coverage. Efforts are needed to understand factors that
      influence gender differences in these delays and to determine whether policy
      reforms eliminate or exacerbate these differences.

PMID- 20800768
TI  - Racial/ethnic disparities in gestational diabetes mellitus: findings from a
      population-based survey.
AB  - PURPOSE: We sought to explore racial/ethnic disparities in the prevalence of
      gestational diabetes mellitus (GDM) in a population-based sample. METHODS: Data
      from the Oregon Pregnancy Risk Assessment Monitoring System (PRAMS), a
      stratified, random sample of postpartum women who delivered in Oregon in 2004 and
      2005 (n = 3,883; weighted response rate, 75.2%) and linked birth certificates
      were analyzed. Hispanic, non-Hispanic Black, non-Hispanic American Indian, and
      non-Hispanic Asian/Pacific Islander (API) women were oversampled. We categorized
      women as having had GDM if they gave an affirmative answer on the birth
      certificate or the PRAMS survey. RESULTS: Non-Hispanic API women had the highest
      prevalence of GDM (14.8%); this was true for women with both a normal and a high
      body mass index (BMI). Asian women were more likely to have had GDM than Pacific
      Islander women. On multivariate analysis, non-Hispanic APIs were significantly
      more likely to have a pregnancy complicated by GDM (adjusted odds ratio, 2.26;
      95% confidence interval, 1.23-4.13) than non-Hispanic White women. CONCLUSION:
      Non-Hispanic API women, especially Asian women with both normal and high BMI,
      have increased risk of GDM. Future research should examine the unique risk
      factors experienced by Asians and health practitioners should be vigilant in
      screening for GDM regardless of BMI.

PMID- 20800769
TI  - Factors affecting the willingness of counselors to integrate preconception care
      into sexually transmitted disease clinics.
AB  - BACKGROUND: The high rate of unintended pregnancy is an immediate barrier to
      providing preconception care (PCC). Failure to deliver additional PCC messages at
      sexually transmitted disease (STD) clinics might represent a major missed
      opportunity to target women at increased risk for unintended pregnancy for
      behaviors that also put them at risk for adverse pregnancy outcomes. METHODS:
      Using a survey questionnaire, we assessed perceptions of PCC and factors
      influencing the willingness of STD counselors to integrate PCC as an intervention
      service provided by the STD clinics of 140 STD counselors. We used a cross
      sectional design and selected survey participants with a minimum of 2 years'
      experience in providing HIV pretest and posttest counseling and syphilis
      interviewing using a nonprobability, purposive sample. RESULTS: The level of
      occupational responsibility and the amount of time available seemed to affect
      counselor perceptions of the importance of PCC and whether it should be
      integrated as an intervention service provided by STD clinics. Findings suggested
      that, although most STD counselors reported that PCC was an important issue,
      there was significant variation in the perception of whether PCC should be
      delivered at STD clinics. CONCLUSION: STD counselors perceived PCC to be an
      important intervention service that can be delivered at STD clinics. Additional
      study is needed to identify factors that might affect full integration into the
      STD clinic setting.

PMID- 20800770
TI  - Adherence to mammography and colorectal cancer screening in women 50-80 years of
      age the role of psychological distress.
AB  - PURPOSE: The purpose of this study was to examine the impact of women's attitudes
      and health beliefs regarding breast and colorectal cancer screening practices.
      METHODS: Nine hundred five women, 50 to 80 years of age, were recruited from 63
      randomly selected physician offices within the greater Los Angeles area. The
      Health Belief Model was used to evaluate potential predictor variables associated
      with patients' breast and colorectal cancer screening practices. RESULTS: The
      study results revealed that mammographic screening compliance was relatively high
      (70%), whereas only 29% of the patients were compliant with fecal occult blood
      test (FOBT) screening guidelines. Women were far more likely to obtain regular
      mammography screening than an FOBT. Psychological distress had one of the
      strongest, negative associations with breast cancer and colorectal cancer
      screening, and was also a prevalent predictor for many of the variables examined.
      CONCLUSION: Psychological distress seems to negatively impact a patient's
      decision to adhere to breast cancer and colorectal cancer screening
      recommendations, although participants were far more likely to obtain regular
      mammography screening than an FOBT.

PMID- 20800771
TI  - Perceived discrimination and health outcomes a gender comparison among Asian
      Americans nationwide.
AB  - OBJECTIVES: We examined whether similarities and differences exist in the
      association between perceived discrimination and poor mental and physical health
      among Asian-American adult women and men. We also tested whether Asian-American
      women would have a lower perceived discrimination threshold for developing
      negative health outcomes than Asian-American men. METHODS: Data were derived from
      the National Latino and Asian-American Study (2002-2003). A nationally
      representative sample of Asian-American adults (1,075 women and 972 men) was
      examined. RESULTS: There were more gender similarities than differences in the
      strong association between discrimination and health. More prominent gender
      differences were found for the specific level of discrimination and its potential
      health effects. Specifically, for both Asian women and men, a high level of
      perceived discrimination showed stronger associations with mental health than
      with physical health outcomes. And yet, compared with men, the threshold of
      discrimination was lower for women in affecting mental and physical health
      status. CONCLUSION: The findings underscore that a high level of discrimination
      was associated with negative mental and physical health outcomes for both women
      and men. However, women had more negative mental and physical health outcomes
      when exposed to a lower threshold of discrimination than men. These findings
      suggest that failing to examine women and men separately in discrimination
      research may no longer be appropriate among the Asian-American population. Future
      research should focus attention on the biological, social, and political
      mechanisms that mitigate the adverse health effects of discrimination in order to
      develop a more comprehensive approach to eliminate disparities in health.

PMID- 20800772
TI  - Dentists' perceptions of barriers to providing dental care to pregnant women.
AB  - PURPOSE: The purpose of the study was to understand US dentists' attitudes,
      knowledge, and practices regarding dental care for pregnant women and to
      determine the impact of recent papers on oral health and pregnancy and guidelines
      disseminated widely. METHODS: In 2006 and 2007, the investigators conducted a
      mailed survey of all 1,604 general dentists in Oregon; 55.2% responded).
      Structural equation modeling was used to estimate associations between dentists'
      attitudes toward providing care to pregnant women, dentists' knowledge about the
      safety of dental procedures, and dentists' current practice patterns. RESULTS:
      Dentist's perceived barriers have the strongest direct effect on current practice
      and might be the most important factor deterring dentists from providing care to
      pregnant patients. Five attitudes (perceived barriers) were associated with
      providing less dental services: time, economic, skills, dental staff resistance,
      and peer pressure. The final model shows a good fit with a chi-square of 38.286
      (p = .12; n = 772; df = 52) and a Bentler-Bonett normed fit index of .98 and a
      comparative fit index of .993. The root mean square error of approximation is
      .02. CONCLUSION: Findings suggest that attitudes are significant determinants of
      accurate knowledge and current practice. Multidimensional approaches are needed
      to increase access to dental care and protect the oral health of women during
      pregnancy. Despite current clinical recommendations to deliver all necessary care
      to pregnant patients during the first, second, and third trimesters, dentists'
      knowledge of the appropriateness of procedures continues to lag the state of the
      art in dental science.

PMID- 20800773
TI  - Survey of knowledge, attitudes, and practice management patterns of Atlanta-area
      obstetricians regarding stillbirth.
AB  - OBJECTIVE: Existing surveillance data on fetal death certificates are suboptimal
      for conducting reliable epidemiologic studies on stillbirth. The objective of
      this survey was to better understand the factors potentially affecting the
      quality of data collected on stillbirths among a defined population. METHODS: A
      survey was mailed to all physicians (n = 661) listed in the July 2007 version of
      the American Medical Association master file with a primary specialty of
      obstetrics/gynecology and a mailing address within five counties in metropolitan
      Atlanta. RESULTS: A total of 487 physicians met eligibility criteria: 279
      returned the survey, 179 did not return the survey, and 29 were returned as
      unable to locate. Two respondents returned incomplete surveys, leaving 277
      participants for the final analysis. Respondents reported seeing an average of
      six stillbirths per year. A cause of death was not identified in two thirds of
      cases. Almost half (46.8%) of participants responded that 20 weeks was the
      minimum gestational age defining stillbirth, whereas 33.1% responded that it was
      24 weeks. A majority (92.6%) responded that a standardized definition for
      stillbirth should be adopted. More than 80% agreed that a comprehensive
      evaluation was important to identify a cause of death, and 91.9% agreed that the
      use of a standardized protocol for post-mortem stillbirth evaluation would be
      helpful. A majority also agreed that ongoing surveillance of stillbirths and a
      national research agenda on causes of stillbirth are important. CONCLUSION:
      Comprehensive educational and awareness efforts for obstetricians and other
      related health care personnel are needed to further improve on the data collected
      for surveillance purposes on stillbirth.

PMID- 20800774
TI  - Should "Dr. S" maintain her American Board of Radiology subspecialty certificate
      in Vascular and Interventional Radiology?

PMID- 20800775
TI  - Vertebroplasty for acute osteoporotic spinal fractures-best evidence?

PMID- 20800776
TI  - Interventional endovascular management of chronic cerebrospinal venous
      insufficiency in patients with multiple sclerosis: a position statement by the
      Society of Interventional Radiology, endorsed by the Canadian Interventional
      Radiology Association.

PMID- 20800777
TI  - Occupational health hazards in the interventional laboratory: progress report of
      the Multispecialty Occupational Health Group.
AB  - The Multispecialty Occupational Health Group (MSOHG), formed in 2005, is an
      informal coalition of societies representing professionals who work in, or are
      concerned with, interventional fluoroscopy. The group's long-term goals are to
      improve occupational health and operator and staff safety in the interventional
      laboratory while maintaining quality patient care and optimal use of the
      laboratory. MSOHG has conducted a dialogue with equipment manufacturers and has
      developed a list of specific objectives for research and development. The group
      has also represented the member societies in educating regulators, in educating
      interventionalists, and in fostering and collaborating on research into
      occupational health issues affecting interventionalists. Not least of the group's
      accomplishments, as a result of their collaboration in MSOHG, the group's members
      have developed a mutual respect that can serve as a basis for joint efforts in
      the future among interventionalists of different medical specialties.

PMID- 20800778
TI  - Significant prostacyclin/thromboxane level imbalance after lower limb arterial
      angioplasty: a possible platelet function alteration.
AB  - PURPOSE: The authors investigated prostacyclin (PGI2) and thromboxane (TX)
      productions in peripheral venous blood after lower limb revascularization by
      percutaneous transluminal angioplasty (PTA) versus diagnostic angiography. The
      purpose of this study was to investigate PGI2/TX imbalance after PTA. This
      imbalance is of pathophysiologic importance and it is a potential sign of
      platelet function alteration. MATERIALS AND METHODS: Twenty-five patients
      requiring PTA were compared with 20 patients undergoing angiography alone from
      April 2004-December 2005 from a single vascular unit. Patient age range was 42-90
      years, and the majority of patients were men. Prostaglandin F2-alpha (PGF2-alpha)
      and thromboxane B2 (TXB2) were measured sequentially (preprocedure, at 1 hour,
      and 24 hours after procedure). Differences between postprocedure and preprocedure
      level were compared statistically between angiography and PTA. RESULTS: Baseline
      demographics were distributed equally between the two groups except presence of
      critical ischemia and ankle brachial pressure index, which were two significant
      confounders. TXB2 was significantly higher after PTA at 1 hour and 24 hours after
      PTA (P = .005 and P = .014 respectively), PGF2-alpha was significantly higher 24
      hours after PTA only (P = .018) (Mann-Whitney U test). CONCLUSIONS: PGI2/TX
      balance homeostasis is of significant pathophysiologic importance. The authors
      found that PTA results in significant PGI2/TX imbalance and shifts more toward
      increased TX production. This finding is partly suggestive of significant
      platelet activation. This imbalance in PGI2/TX level may have implications for
      future failure of PTA. Future research in reducing this platelet activation is
      recommended.

PMID- 20800779
TI  - Clinical course of pain in acute osteoporotic vertebral compression fractures.
AB  - PURPOSE: The authors prospectively determined the natural course of pain in
      patients with conservatively treated acute osteoporotic vertebral compression
      fractures (VCF). In addition, the type of conservative therapy that these
      patients received was assessed. MATERIALS AND METHODS: Patients older than 50
      years, referred for spine radiography for acute back pain, were asked to complete
      a baseline clinical questionnaire. Patients with an acute VCF were followed up at
      6 and 23 months with a questionnaire that included a Visual Analog Score (VAS)
      and type of pain medication and other conservative treatment. Significant pain
      relief was defined as a decrease in VAS of 50% or more. RESULTS: Forty-nine
      patients (mean age, 78 years; range, 51-95) with acute VCF were followed up for
      almost 2 years. Significant pain relief was noted in 22 of 35 patients (63%) at 6
      months and in 25 of 36 (69%) at 23 months. In patients with persisting pain at 23
      months (mean VAS 6.4), some decrease in VAS was apparent at 6 months but not in
      the 6-23 months interval. No predictors for significant pain relief could be
      identified. Patients with significant pain relief used less pain medication and
      had less physical therapy. CONCLUSIONS: In most patients with an acute VCF, pain
      decreases significantly with conservative therapy, predominantly in the first 6
      months. However, almost 2 years after an acute VCF, a third of patients still had
      severe pain necessitating pain medication and physical therapy in the majority.
      No predictors for transition from acute to chronic pain could be identified.

PMID- 20800780
TI  - Prospective evaluation of a newly designed T-configured stent graft system for
      palliative treatment of advanced hilar malignant biliary obstructions.
AB  - PURPOSE: To investigate the technical and clinical safety and efficacy of using a
      newly designed T-configured stent graft for palliative treatment of advanced
      hilar malignant biliary obstructions. MATERIALS AND METHODS: This is a
      prospective study that enrolled 30 patients who had malignant hilar obstructions
      from May 2007 to November 2008. All patients were treated with percutaneous
      transhepatic placement of two specially designed stent grafts in a T
      configuration. Technical success, evaluation of blocked branching ducts,
      complications, clinical success, stent patency time, and patient survival rates
      were analyzed. RESULTS: Stent graft deployment was technically successful in all
      patients. The bilirubin level and the bile duct diameter decreases were
      statistically significant after stent placement (P < .001), and all patients
      showed clinical improvement. Minor complications, including procedure-related
      complications (self-limiting hemobilia [n = 3], perihepatic biloma [n = 1], and
      acute pancreatitis [n = 1]) and rapidly resolving cholangitis (n = 5), occurred
      in ten patients (33.3%). Major complications, including acute cholecystitis,
      occurred in three patients (10%). Stent occlusion occurred in 12 patients (40%)
      after a mean period of 160 days (range, 82-307 days). The median survival and
      stent patency times were 334 days (range, 195.6-472.4 days) and 279 days (range,
      194.7-363.3 days), respectively. There were no statistical differences in age,
      sex, Bismuth type, or number of blocked branching ducts. CONCLUSIONS: The initial
      results of percutaneous palliative treatment of advanced hilar malignancies with
      T-configured stent grafts suggest that they are safe and potentially clinically
      effective.

PMID- 20800781
TI  - Percutaneous osteoplasty with a bone marrow nail for fractures of long bones:
      experimental study.
AB  - PURPOSE: To develop percutaneous osteoplasty with the use of a bone marrow nail
      for fixation of long-bone fractures, and to evaluate its feasibility and safety
      in vivo and in vitro. MATERIALS AND METHODS: Six long bones in three healthy
      swine were used in the in vivo study. Acrylic cement was injected through an 11
      gauge bone biopsy needle and a catheter into a covered metallic stent placed
      within the long bone, creating a bone marrow nail. In the in vitro study, we
      determined the bending, tug, and compression strengths of the acrylic cement
      nails 9 cm long and 8 mm in diameter (N = 10). The bending strength of the
      artificially fractured bones (N = 6) restored with the bone marrow nail and
      cement augmentation was then compared with that of normal long bones (N = 6).
      RESULTS: Percutaneous osteoplasty with a bone marrow nail was successfully
      achieved within 1 hour for all swine. After osteoplasty, all swine regained the
      ability to run until they were euthanized. Blood tests and pathologic findings
      showed no adverse effects. The mean bending, tug, and compression strengths of
      the nail were 91.4 N/mm(2) (range, 75.0-114.1 N/mm(2)), 20.9 N/mm(2) (range, 6.6
      30.4 N/mm(2)), and 103.0 N/mm(2) (range, 96.3-110.0 N/mm(2)), respectively. The
      bending strength ratio of artificially fractured bones restored with bone marrow
      nail and cement augmentation to normal long bone was 0.32. CONCLUSIONS:
      Percutaneous osteoplasty with use of a bone marrow nail and cement augmentation
      appears to have potential in treating fractures of non-weight-bearing long bones.

PMID- 20800782
TI  - Percutaneous transrenal embolization of vascular complication of nephrostomy.

PMID- 20800783
TI  - QRS in pigs versus in dogs.

PMID- 20800785
TI  - The role of vitamin D in asthma.
AB  - OBJECTIVE: To review the current literature on vitamin D and asthma, discussing
      the possible roles of vitamin D on asthma pathogenesis and the potential
      consequences of vitamin D deficiency. DATA SOURCES: PubMed database was searched
      from 1950 to 2009. Keywords used included asthma, vitamin D, inflammation, airway
      smooth muscle and cytokines. STUDY SELECTION: Articles were selected based on
      relevance to the subject. RESULTS: Vitamin D deficiency has been associated with
      epidemiologic patterns observed in the asthma epidemic. Vitamin D deficiency is
      more common with obesity, African American ethnicity, and westernization of
      countries with higher-risk populations for asthma. Evidence suggests that vitamin
      D deficiency is associated with increased airway hyperresponsiveness, lower
      pulmonary functions, worse asthma control, and possibly steroid resistance. Lung
      epithelial cells express high baseline levels of 1alpha-hydroxylase. This allows
      the conversion of inactive calcidiol to active calcitriol locally within the
      lung. Calcitriol has been shown to inhibit the synthesis and release of certain
      cytokines, such as RANTES, platelet-derived growth factor, and matrix
      metalloproteinases, from bronchial smooth muscle cells, thereby leading to
      decreased lung inflammation and smooth muscle cell proliferation. Vitamin D also
      increases synthesis of interleukin 10 by CD4+CD25+Foxp3+ T-regulatory cells and
      dendritic cells, while concurrently inhibiting dendritic cell activation by
      downregulating expression of costimulatory molecules CD40 and CD80/86. Vitamin D
      is also capable of inducing the expression of several anti-infective molecules,
      such as cathelicidin. Thus, vitamin D has a number of biologic effects that are
      likely important in regulating key mechanisms in asthma. CONCLUSIONS: We
      hypothesize that vitamin D supplementation may lead to improved asthma control by
      inhibiting the influx of inflammatory cytokines in the lung and increasing the
      secretion of interleukin 10 by T-regulatory cells and dendritic cells.

PMID- 20800786
TI  - Development of a nomogram for identification of asthma among adults in
      epidemiologic studies.
AB  - BACKGROUND: The criteria used to identify persons with asthma in epidemiologic
      studies are varying and, depending on the method used, can be challenging and
      resource consuming. OBJECTIVE: To develop a nomogram (scoring system) to identify
      adult patients with asthma using a combination of variables collected via a
      validated questionnaire. METHODS: We studied the first 268 women aged 40 to 69
      years in the Shanghai Women's Asthma and Allergy Study who reported signs and
      symptoms of asthma and underwent either methacholine challenge testing or test of
      reversibility during the asthma screening survey between 2003 and 2007. These
      women were defined as having definite asthma (n=106) or not (n=162).
      Multivariable logistic regression analysis was performed to develop a predictive
      model for identifying asthma using survey information alone. RESULTS: Clinically
      relevant questions were used for the predictive multivariable logistic regression
      model and included the following: ever wheezing or whistling in the chest,
      current medication use for asthma, self-reported ever asthma, self-reported ever
      allergic rhinitis, family history of allergy, and age. The area under the
      receiver operating characteristic curve of the prediction model was 0.75 (95%
      confidence interval, 0.69-0.81). A nomogram was developed to assess the
      individual probability of asthma based on individually weighted variables in the
      predictive model. CONCLUSIONS: In clinical or epidemiologic studies, this asthma
      nomogram could be used as a tool to assess the probability of asthma for an
      individual patient by incorporating asthma-related predictor variables obtained
      through a field questionnaire.

PMID- 20800787
TI  - Risk of perinatal mortality associated with asthma during pregnancy: a 2-stage
      sampling cohort study.
AB  - BACKGROUND: The association between maternal asthma during pregnancy and
      perinatal mortality has been investigated in 21 studies, and a significantly
      increased risk among asthmatic women was found in 4 studies. However, these
      studies have methodologic limitations, such as lack of adjustment for cigarette
      smoking, a major risk factor for perinatal mortality. OBJECTIVE: To evaluate
      whether maternal asthma during pregnancy increases the risk of perinatal
      mortality. METHODS: From the linkage of 3 administrative databases from Quebec,
      Canada, a cohort including 13,100 asthmatic and 28,042 nonasthmatic women who had
      at least 1 pregnancy between 1990 and 2002 was constructed. We used a 2-stage
      sampling cohort design to obtain information on cigarette smoking and other
      potential confounders from the medical records of 1,247 selected mothers.
      RESULTS: In the cohort, 353 cases of perinatal mortality were identified, and we
      were able to retrieve the medical record of the mother for 304 cases. A
      significantly increased crude risk of perinatal mortality of 34% among asthmatic
      women compared with nonasthmatic women was found, but the odds ratio did not
      remain significant after adjustment for placental abruption and cigarette smoking
      (odds ratio, 1.12; 95% confidence interval, 0.87-1.45). CONCLUSION: The risk of
      perinatal mortality was not found to be significantly associated with maternal
      asthma after the effect of smoking was removed.

PMID- 20800788
TI  - Premenstrual asthma and atopy markers.
AB  - BACKGROUND: The frequency of atopy in women with premenstrual asthma (PMA) and
      its possible effect on the premenstrual exacerbation of asthma are unknown.
      OBJECTIVE: To analyze the relation between atopy markers (total IgE, Phadiatop,
      and specific IgE) and PMA. METHODS: Asthmatic women of reproductive age completed
      a questionnaire about respiratory symptoms and recorded peak flow during an
      entire menstrual cycle to be classified as asthmatic patients with or without
      PMA. Their asthma severity was graded according to the 2005 Global Initiative for
      Asthma scale. PMA was defined as a clinical or functional exacerbation (>or=20%)
      in the premenstrual phase compared with the preovulatory phase. Blood tests for
      several atopy markers were conducted for: total IgE and screening for
      aeroallergens (Phadiatop) and specific IgE. RESULTS: Blood determinations were
      performed in 59 asthmatic women, of whom 31 (53%) had PMA. Twenty-six patients
      with PMA (84%) and 12 without PMA (43%) had total IgE values greater than 100
      kU/L (P=.001). Twenty-one patients with PMA (68%) and 14 without PMA (50%) tested
      positive for Phadiatop (P=.17). Those who were positive for Phadiatop were also
      tested for specific IgE. No relation was found between specific IgE and PMA;
      values for ryegrass (63%), olive (60%), and Dermatophagoides pteronyssinus (54%)
      exceeded 0.35 kU/L. CONCLUSIONS: PMA seems to be closely linked to total IgE
      levels but not to specific allergens. The atopy affects the clinical
      manifestations of PMA in women of reproductive age.

PMID- 20800789
TI  - Bridging allergologic and botanical knowledge in seasonal allergy: a role for
      phenology.
AB  - BACKGROUND: Grass pollen is a worldwide cause of respiratory allergy. Identifying
      the causative species is essential, for example for choosing the appropriate
      immunotherapy, because not all grass allergens are totally cross-reacting, and
      the pollen calendars provide only a gross estimate. Phenologic analyses allow
      identification of the pollen release for each individual grass. OBJECTIVES: To
      assess, using phenologic analyses, the true flowering periods of grasses and to
      compare the data with the standard pollen calendar. METHODS: Phenologic analyses
      were performed of the following grasses: black grass, sweet vernal grass, common
      wild oat, barren brome, cocksfoot, tall fescue, Yorkshire fog, ryegrass, Timothy
      grass, bulbous meadow-grass, Kentucky bluegrass, and Bermuda grass. Sampling was
      performed every 10 days, starting in April 2009, at 50 stations distributed
      across Italy. The flowering phase was assessed using a stereomicroscopy-based
      method for the detection of spreading stamens. The official pollen calendar was
      used for comparison. RESULTS: Relevant differences were found between grass
      pollen count and effective flowering of the grass species. Only some species
      contributed to the pollen peak, and a relevant pollen load for other species was
      also present out of the peak. Important Pooideae, such as Timothy grass, were not
      present during the pollen peak in northern and central Italy, and the same
      occurred with Bermuda grass. CONCLUSIONS: The various species of grasses release
      their pollen grains at different times during the pollen season, and this
      information is missing with pollen calendars. This may have a relevant effect on
      the choice of an appropriate immunotherapy.

PMID- 20800790
TI  - Dog characteristics and allergen levels in the home.
AB  - BACKGROUND: Comprehensive analyses on the effect of household dogs on dog
      allergen levels in the home are lacking. OBJECTIVE: To identify environmental
      factors and dog-specific characteristics that influence the accumulation of Canis
      familiaris 1 (Can f 1) in homes. METHODS: Dust samples were collected from the
      floor of infants' bedrooms at a Wayne County Health, Environment, Allergy, &
      Asthma Longitudinal Study birth cohort study home visit and processed for Can f 1
      using a standardized protocol. Dog characteristics were based on maternal report.
      Homes with 1 dog were included in detailed analyses, including characterization
      of the dog based on coat type, dander level, and shedding. RESULTS: Households
      with dogs had higher levels of dog allergen in the home than those without dogs;
      however, the number of dogs in the home was not related to dog allergen levels.
      Homes with exclusively outdoor dogs had significantly higher dog allergen levels
      than homes without any dogs but significantly lower levels of dog allergen than
      homes with indoor dogs. Homes where the dog was allowed in the infant's bedroom
      had significantly higher Can f 1 levels on the child's bedroom floor than homes
      where it was not. The homes of altered dogs had higher Can f 1 levels than did
      their unaltered counterparts. CONCLUSIONS: Dogs in the home corresponded to dog
      allergen in the home. Time the dog was indoors and whether it was allowed on the
      vacuumed surface mattered. No dog characteristic, other than altered status, was
      associated with allergen levels in the home.

PMID- 20800792
TI  - Anaphylaxis induced by fosfomycin.

PMID- 20800791
TI  - Induction of interleukin 8 by American cockroach allergens from human airway
      epithelial cells via extracellular signal regulatory kinase and jun N-terminal
      kinase but not p38 mitogen-activated protein kinase.
AB  - BACKGROUND: Cockroaches are potent aeroallergens associated with asthma. Several
      reports suggest that a novel group of G protein-linked receptors, protease
      activated receptors (PARs), may be involved in the intracellular signaling
      pathway induced by aeroallergens of the epithelial cells. OBJECTIVE: To
      investigate the mechanisms of American cockroach allergens (CraA) on interleukin
      8 (IL-8) in human pulmonary epithelial cells. METHODS: Protease activities of
      CraA were quantified by the Azocoll method. The gene and protein expressions of
      IL-8 from CraA-stimulated A549 cells were quantified by real-time polymerase
      chain reaction and enzyme-linked immunosorbent assay, respectively. The activity
      of different mitogen-activated protein kinases (MAPKs) was assessed by Western
      blot. RESULTS: CraA-induced A549 cell IL-8 secretion in a dose-dependent manner
      at both the messenger RNA and protein levels. CraA-induced IL-8 secretion can be
      blocked by serine protease inhibitors, phenylmethane sulfonyl fluoride, and
      aprotinin but not by other protease inhibitors. Blocking antibodies against the
      cleavage sites of PAR-2 and PAR-3, but not of PAR-1, inhibited CraA-induced IL-8
      production. CraA induced significant PAR-2 and PAR-3 messenger RNA upregulation
      and extracellular-regulated kinase (ERK/1/2) and Jun N-terminal kinase (JNK)
      phosphorylation but not p38 MAPK. Furthermore, ERK1/2 (U0126) and JNK (SP600125)
      inhibitors inhibited CraA-induced IL-8 secretion by 100% and 45%, respectively.
      CONCLUSIONS: Both PAR-2 and PAR-3 might play a role in CraA-induced IL-8
      secretion from human airway epithelial cells. It signals mainly through the
      ERK1/2 and partly from the JNK pathways. The key receptors and signaling
      molecules mediate cytokine release from the respiratory epithelium and can be
      potential therapeutic targets in treating cockroach allergy.

PMID- 20800793
TI  - Acute generalized exanthematous pustulosis: the first pediatric case caused by a
      contrast agent.

PMID- 20800794
TI  - Returning the athlete to sports after a near-fatal asthma event.

PMID- 20800796
TI  - Multiple treatment cycles of high-dose intravenous immunoglobulin for chronic
      spontaneous urticaria.

PMID- 20800797
TI  - Hiding in plain sight: a case of Tarlov perineural cysts.

PMID- 20800798
TI  - Clopidogrel resistance: what's new?
AB  - The concept of clopidogrel resistance emerged several years ago. Since then, many
      studies have been performed to elucidate the mechanisms and potential clinical
      impact of this biological finding. These studies identified complex mechanisms,
      including drug-drug interactions, genetic polymorphisms and clinical factors, and
      showed consistently the clinical relevance of the variability of clopidogrel
      response, with higher ischaemic risk in low-responders or non-responders, and
      higher bleeding risk in hyper-responders. Several strategies for overcoming
      clopidogrel resistance have been evaluated in small clinical studies, but the
      benefit of tailored antiplatelet therapy has yet to be validated in large
      randomized trials, which are currently ongoing. Upcoming antiplatelet drugs that
      are more potent will change the field of antiplatelet therapy in acute coronary
      syndromes. The future of antiplatelet therapy sounds more complex, with different
      drugs, and tailored therapy based on platelet tests and/or genetic testing, but
      it will lead us to propose a more individualized therapy, which hopefully will
      improve patient outcome.

PMID- 20800800
TI  - Evidence-based pharmacotherapy after myocardial infarction in France: adherence
      associated factors and relationship with 30-month mortality and
      rehospitalization.
AB  - BACKGROUND: International guidelines recommend long-term use of evidence-based
      treatment (EBT) combining beta-blockers, aspirin/clopidogrel, statins and either
      angiotensin-converting enzyme inhibitors or angiotensin receptor blockers
      (ACEIs/ARBs) after a myocardial infarction (MI), to reduce cardiac morbidity and
      mortality. AIMS: To evaluate medication adherence after hospital admission for MI
      and the relationship with mortality and readmission for acute coronary syndrome.
      METHODS: Observational, 30-month follow-up of patients admitted for acute MI in
      France in the first half of 2006 and still alive 6 months later. Data from the
      national hospital discharge database and the outpatient medications reimbursement
      database were linked for all patients covered by the general health insurance
      scheme (70% of the French population). A patient was considered as adherent when
      the proportion of days covered by a filled prescription was greater than 80%.
      RESULTS: The proportion of nonadherent patients was 32.0% for beta-blockers,
      24.0% for statins, 22.7% for ACEIs/ARBs, 18.3% for aspirin/clopidogrel and 50.0%
      for combined EBT. Adherence to EBT was decreased significantly by age greater
      than 74 years, comorbidities and full healthcare coverage for low earners. Prior
      EBT use and stent implantation, before or during index hospitalization, increased
      adherence. After adjustment for patient characteristics and management, prior use
      of each class decreased mortality. Nonadherence to EBT after MI increased
      mortality and readmission (hazard ratio=1.43, P<0.0001). CONCLUSION: After MI,
      nonadherence to EBT is associated with a marked increase in all-cause mortality
      and readmission for acute coronary syndrome. Cost-effective strategies for
      adherence improvement should be developed among patient groups with poor
      adherence.

PMID- 20800799
TI  - Distribution of left ventricular ejection fraction and heart rate values in a
      cohort of stable coronary patients: the INDYCE registry.
AB  - BACKGROUND: The distribution of left ventricular ejection fraction (LVEF) - a key
      factor in coronary artery disease (CAD) patient management and prognostication -
      is poorly documented. OBJECTIVE: To determine LVEF and heart rate (HR) values,
      and describe the management of stable CAD patients in France. METHODS: The INDYCE
      survey was a prospective, multicentre registry of consecutive stable CAD
      outpatients attending a cardiology consultation. The survey focused on LVEF
      values measured using the echocardiographic Simpson biplane method. Drug therapy,
      resting HR, blood pressure and symptoms were also recorded. RESULTS: Overall,
      3119 patients (68.4 +/- 11.0 years; 80% men) were enrolled. LVEF was 56.1+/-11.8%
      on average, and was poor (<40%) and moderately impaired (40-50%) in 9.6% (n=298)
      and 19.8% (n=619) of cases, respectively. Symptomatic angina pectoris was present
      in 19.2% of cases and only 40.6% of patients were asymptomatic (no angina and
      NYHA class < or = I) despite relatively aggressive management (79.0% of patients
      had undergone coronary angioplasty and/or bypass graft). Interestingly, 14.1% of
      patients with LVEF less than 40% were asymptomatic. In multivariable analysis,
      LVEF less than 40% was associated most strongly with symptomatic status (odds
      ratio 3.82; 95% CI 2.59-5.63; P<0.0001), together with female sex, age greater
      than 75 years, diabetes, HR greater or equal to 70 bpm, sedentariness, obesity
      and disease duration. CONCLUSION: Only 9.6% of stable CAD patients had severe
      left ventricular dysfunction; among them, 14.1% were strictly asymptomatic. This
      could justify regular LVEF measurement in CAD patients. Three potentially
      reversible factors (HR>or=70 bpm, being overweight and sedentariness) were linked
      independently to the presence of symptoms.

PMID- 20800802
TI  - Cryoballoon for pulmonary vein isolation: Is it better tolerated than
      radiofrequency? Retrospective study comparing the use of analgesia and sedation
      in both ablation techniques.
AB  - BACKGROUND: Treatment of atrial fibrillation (AF) by radiofrequency or
      cryoballoon ablation requires good sedation and effective analgesia to be carried
      out safely and successfully. AIM: To compare analgesic and sedative drug usage
      during ablation procedures for paroxysmal AF. METHODS: The records of 60 patients
      hospitalized for ablation of paroxysmal AF were studied. Patients were divided
      into two groups, according to the technique used: radiofrequency ablation (group
      A) and cryoballoon ablation (group B). Anaesthetic and sedative medication usage
      was compared between groups. RESULTS: Patients' mean age was 56.2 +/- 1 years in
      the radiofrequency group and 57.0 +/- 0.74 years in the cryoballoon group; mean
      duration of AF was 6.91+/-2.36 and 6.77 +/- 2.51 years, respectively. Twenty
      patients from group A and 18 from group B had transesophageal echocardiography.
      With regard to sedative use, 3.01 +/- 1.3 mg/m(2) of midazolam was used in group
      A versus 3.5 +/- 1.26 mg/m(2) in group B (p=0.14). Propofol was seldom used. For
      analgesia, 0.31 +/- 0.26 g/m(2) of paracetamol was used in group A versus 0.73 +/
      1.86 g/m(2) in group B (p=0.23). Mean morphine dose was higher in group A versus
      group B (3 +/- 1.5 vs 2.09 +/- 1.02 mg/m(2), respectively; p=0.01). CONCLUSION:
      In this study, patients who underwent cryoballoon ablation required a lower dose
      of morphine compared with those who underwent radiofrequency ablation. Catheter
      cryoballoon ablation appears better tolerated than radiofrequency ablation for
      the treatment of paroxysmal AF.

PMID- 20800803
TI  - Factors influencing the level of circulating procoagulant microparticles in acute
      pulmonary embolism.
AB  - BACKGROUND: Flow cytometry has shown levels of platelet-derived microparticles
      (PMPs) and endothelial-derived microparticles (EMPs) to be elevated in deep-vein
      thrombosis. Cardiovascular risk factors can also contribute to hypercoagulability
      due to circulating procoagulant microparticles (CPMPs). AIMS: To investigate in a
      case-control study the respective contribution of pulmonary embolism and
      cardiovascular risk factors to the level of hypercoagulability due to CPMPs.
      METHODS: CPMP, PMP and EMP levels were measured in 45 consecutive patients (age
      67.9 +/- 11.6 years; 66.7% men) admitted to an intensive care unit for acute
      pulmonary embolism (APE), 45 healthy control subjects with no history of venous
      thromboembolism or vascular risk factors (Controls(noCVRFs)), and 45 patients
      with cardiovascular risk factors (Controls(CVRFs)). APE was diagnosed by spiral
      computed tomography or scintigraphy. CPMP levels were assessed using a
      prothrombinase assay on platelet-depleted plasma (results expressed as nmol/L
      equivalent). RESULTS: CPMP levels were higher in APE patients than in
      Controls(noCVRFs) (medians 4.7 vs 3.2 nmol/L, interquartile ranges [IQRs] 2.9
      11.1 vs 2.3-4.6 nmol/L; p=0.02). Similar results were reported for PMPs (medians
      2.2 vs 1.9 nmol/L, IQRs 1.7-5.8 vs 1.4-2.4 nmol/L; p=0.02), whereas EMP levels
      were not significantly different. However, CPMP procoagulant activity was not
      significantly different in APE patients and Controls(CVRFs). CONCLUSIONS: CPMPs
      and PMPs were significantly elevated in APE patients vs Controls(noCVRFs), but
      this correlation was not significant when APE patients were compared with
      Controls(CVRFs). Our observations highlight the importance of adjusting for the
      presence of cardiovascular risk factors in conditions in which microparticle
      levels are raised.

PMID- 20800804
TI  - Is cardiac resynchronization therapy an option in heart failure patients with
      preserved ejection fraction? Justification for the ongoing KaRen project.
AB  - The relevance of electrical and mechanical dyssynchrony has been demonstrated in
      heart failure with reduced ejection fraction. Preserved ejection fraction is
      present in as many as 50% of patients with chronic heart failure. Recent small
      studies suggest that both electrical and mechanical left ventricular dyssynchrony
      are sometimes present in patients with heart failure and preserved ejection
      fraction (HFPEF). These data remain controversial and a robust validation of this
      hypothesis has to be achieved. In the present paper, we review in detail the
      concepts and try to justify the ongoing KaRen registry. This is a prospective,
      multicentre, international, observational study to characterize the prevalence of
      electrical or mechanical dyssynchrony in HFPEF and the resultant effect on
      prognosis. Patients are enrolled currently at the time of an acute congestive
      episode. The diagnosis of HFPEF is made according to clinical data, natriuretic
      peptides and echocardiography for the measurement of ejection fraction. Once
      stabilized, patients return for a hospital check-up. They undergo clinical and
      biological evaluation, electrocardiography and Doppler echocardiography.
      Thereafter, patients are followed every six months, for at least 18 months for
      mortality, and heart failure-related and non-cardiovascular hospitalizations.
      KaRen aims to characterize electrical and mechanical dyssynchrony and to assess
      its prognostic impact in HFPEF. The results may improve our understanding of
      HFPEF and generate answers to the question of whether or not dyssynchrony could
      be a target for cardiac resynchronization therapy in HFPEF.

PMID- 20800805
TI  - Problems in the organization of care for patients with adult congenital heart
      disease.
AB  - The prevalence of congenital heart disease among adults in Europe, or in any
      country in Europe, is not known. This is due to a lack of agreement on the
      incidence of congenital heart disease, with estimations varying from four per
      1000 births to 50 per 1000 births, and it is not known how many patients with
      congenital heart disease have died. Based on several studies that estimated and
      calculated the number of adult patients with congenital heart disease, the number
      of patients should be much higher than the number of patients that are actually
      seen in specialized centres throughout Europe. This implies that either a large
      proportion of adult patients with congenital heart disease do not receive
      appropriate medical care, or that the calculations and estimations are grossly
      wrong. A combination of the two is also possible. A substantial expansion of the
      number and size of specialized centres for adult congenital heart disease is
      advocated, but since setting up (and running) a service for this disease is a
      costly affair, and because uncertainty remains about the actual number of
      patients needing specialized care, this has been difficult to realize in most
      European countries in the past few years.

PMID- 20800806
TI  - Pacemaker endocarditis: approach to lead management.

PMID- 20800807
TI  - Transcatheter closure of a traumatic ventricular septal defect.

PMID- 20800808
TI  - Unusual evolution of an aneurysm of the proximal left anterior descending
      coronary artery 15 years after a Simpson atherectomy.

PMID- 20800801
TI  - Characteristics and management of outpatients with history of or current atrial
      fibrillation: the observational French EPHA study.
AB  - BACKGROUND: Limited French data are available for the different clinical types
      (paroxysmal, persistent and permanent) of atrial fibrillation and their
      comorbidities (AF). AIMS: To provide contemporary insights into the
      characteristics and management of outpatients with a history of or current AF in
      France. METHODS: EPHA is a national, observational, cross-sectional, multicentre
      descriptive study with retrospective data collection relating to the management,
      treatment and hospitalization of patients with AF. RESULTS: One thousand three
      hundred and thirty-one patients (mean age: 74 +/- 11 years [55.7% > or =75
      years]; 58.8% men) were included into the study between February 2009 and May
      2009; their data were collected during the past 12 months. Of these, 38.2% had
      paroxysmal AF, 10.0% persistent AF and 51.8% permanent AF. Most patients had at
      least one cardiovascular risk factor (80.8%). Almost all patients (96.6%) had
      received an antiarrhythmic drug in the previous year, of which 59.6% received a
      rhythm control strategy (class I, class III) with or without rate control
      strategy (class II, class IV, digitalis) and 40.6% received a rate control
      strategy exclusively. Almost all (94.4%) patients were treated with an
      antithrombotic: 83.4% with a vitamin K antagonist and 21.9% with antiplatelet
      therapy. Almost one-fifth (18.4%) of patients had been hospitalized related to AF
      at least once in the previous year. Patients with paroxysmal and persistent AF
      were hospitalized more frequently (20.0% and 31.1%, respectively) than patients
      with permanent AF (14.8%). CONCLUSIONS: About half of the patients had paroxysmal
      or persistent AF. Four-fifths of AF patients had at least one cardiovascular risk
      factor. The use of antiarrhythmic and antithrombotic treatments was very high.
      The rhythm control strategy was preferred in patients with paroxysmal or
      persistent AF.

PMID- 20800809
TI  - Right pneumothorax resulting from an atrial lead inserted through the left
      cephalic vein.

PMID- 20800810
TI  - The development of T-cell immunity.

PMID- 20800811
TI  - Genome duplication and T cell immunity.
AB  - The adaptive immune system (AIS) mediated by T cells and B cells arose ~450
      million years ago in a common ancestor of jawed vertebrates. This system was so
      successful that, once established, it has been maintained in all classes of jawed
      vertebrates with only minor modifications. One event thought to have contributed
      to the emergence of this form of AIS is two rounds of whole-genome duplication.
      This event enabled jawed vertebrate ancestors to acquire many paralogous genes,
      known as ohnologs, with essential roles in T cell and B cell immunity. Ohnologs
      encode the key components of the antigen presentation machinery and signal
      transduction pathway for lymphocyte activation as well as numerous transcription
      factors important for lymphocyte development. Recently, it has been discovered
      that jawless vertebrates have developed an AIS employing antigen receptors
      unrelated to T/B cell receptors, but with marked overall similarities to the AIS
      of jawed vertebrates. Emerging evidence suggests that a common ancestor of all
      vertebrates was equipped with T-lymphoid and B-lymphoid lineages.

PMID- 20800812
TI  - Questions arising from "genome duplication and T cell immunity".

PMID- 20800814
TI  - The origin and role of MHC class I-associated self-peptides.
AB  - Under steady-state conditions, cell surface major histocompatibility complex
      (MHC) I molecules are associated with self-peptides collectively referred to as
      the self-MHC I immunopeptidome (SMII). The SMII regulates all key events that
      occur during the lifetime of CD8 T cells in the thymus and in the periphery. The
      SMII derives mainly from rapidly degraded proteins and contains a tissue-specific
      signature. Peptide-source proteins derive from all cell compartments but are
      enriched in RNA- and DNA-binding proteins, cyclins and cyclin-dependent kinases,
      ribosomal constituents, and chaperones. Cell stress, infection, and
      transformation can modify the repertoire of peptides in the SMII. Constitutive
      MHC I presentation of self-peptides is fraught with the risk of autoimmunity, and
      there is the need for complex self-tolerance mechanisms. However, self
      peptide/MHC I complexes are essential for the development of "classic adaptive"
      TCRalphabeta CD8 T cells and directly contribute to CD8 T-cell responses against
      pathogens and transformed cells.

PMID- 20800815
TI  - Questions arising from "the origin and role of MHC class I-associated self
      peptides".

PMID- 20800818
TI  - Transcriptional regulation of thymus organogenesis and thymic epithelial cell
      differentiation.
AB  - Transcriptional regulatory networks are the central regulatory mechanisms that
      control organ identity, patterning, and differentiation. In the case of the
      thymus, several key transcription factors have been identified that are critical
      for various aspects of thymus organogenesis and thymic epithelial cell (TEC)
      differentiation. The thymus forms from the third pharyngeal pouch endoderm during
      embryogenesis. Organ development progresses from initial thymus cell fate
      specification, through multiple stages of TEC differentiation and cortical (cTEC)
      and medullary (mTEC) formation. Transcription factors have been identified for
      each of these stages: a Hoxa3-dependent cascade at initial fate specification,
      Foxn1 for early (and later) TEC differentiation, and NF-kappaB for mTEC
      differentiation. As important as these factors are, their interrelationships are
      not understood, and many more transcription factors are likely required for
      complete thymus organogenesis to occur. In this chapter, we review the literature
      on these known genes, as well as identify gaps in our knowledge for future
      studies.

PMID- 20800819
TI  - Early T cell differentiation lessons from T-cell acute lymphoblastic leukemia.
AB  - T cells develop from bone marrow-derived self-renewing hematopoietic stem cells
      (HSC). Upon entering the thymus, these cells undergo progressive commitment and
      differentiation driven by the thymic stroma and the pre-T cell receptor (pre
      TCR). These processes are disrupted in T-cell acute lymphoblastic leukemia (T
      ALL). More than 70% of recurring chromosomal rearrangements in T-ALL activate the
      expression of oncogenic transcription factors, belonging mostly to three
      families, basic helix-loop-helix (bHLH), homeobox (HOX), and c-MYB. This
      prevalence is indicative of their importance in the T lineage, and their dominant
      mechanisms of transformation. For example, bHLH oncoproteins inhibit E2A and HEB,
      revealing their tumor suppressor function in the thymus. The induction of T-ALL,
      nonetheless, requires collaboration with constitutive NOTCH1 signaling and the
      pre-TCR, as well as loss-of-function mutations for CDKN2A and PTEN.
      Significantly, NOTCH1, the pre-TCR pathway, and E2A/HEB proteins control critical
      checkpoints and branchpoints in early thymocyte development whereas several
      oncogenic transcription factors, HOXA9, c-MYB, SCL, and LYL-1 control HSC self
      renewal. Together, these genetic lesions alter key regulatory processes in the
      cell, favoring self-renewal and subvert the normal control of thymocyte
      homeostasis.

PMID- 20800817
TI  - Functional development of the T cell receptor for antigen.
AB  - For over three decades now, the T cell receptor (TCR) for antigen has not ceased
      to challenge the imaginations of cellular and molecular immunologists alike. T
      cell antigen recognition transcends every aspect of adaptive immunity: it shapes
      the T cell repertoire in the thymus and directs T cell-mediated effector
      functions in the periphery, where it is also central to the induction of
      peripheral tolerance. Yet, despite its central position, there remain many
      questions unresolved: how can one TCR be specific for one particular peptide
      major histocompatibility complex (pMHC) ligand while also binding other pMHC
      ligands with an immunologically relevant affinity? And how can a T cell's extreme
      specificity (alterations of single methyl groups in their ligand can abrogate a
      response) and sensitivity (single agonist ligands on a cell surface are
      sufficient to trigger a measurable response) emerge from TCR-ligand interactions
      that are so low in affinity? Solving these questions is intimately tied to a
      fundamental understanding of molecular recognition dynamics within the many
      different contexts of various T cell-antigen presenting cell (APC) contacts: from
      the thymic APCs that shape the TCR repertoire and guide functional
      differentiation of developing T cells to the peripheral APCs that support
      homeostasis and provoke antigen responses in naive, effector, memory, and
      regulatory T cells. Here, we discuss our recent findings relating to T cell
      antigen recognition and how this leads to the thymic development of foreign
      antigen-responsive alphabetaT cells.

PMID- 20800820
TI  - Lymphoid tissue inducer cells and the evolution of CD4 dependent high-affinity
      antibody responses.
AB  - Phylogeny indicates that in mammals memory CD4-dependent antibody responses
      evolved after monotremes split from the common ancestor of marsupial and
      eutherian mammals. This was strongly associated with the development of
      segregated B and T cell areas and the development of a linked lymph node network.
      The evolution of the lymphotoxin beta receptor in these higher mammals was key to
      the development of these new functions. Here, we argue that lymphoid tissue
      inducer cells played a pivotal role not only in the development of organized
      lymphoid structures but also in the subsequent genesis of the CD4-dependent class
      switched memory antibody responses that depend on an organized infrastructure to
      work. In this review, we concentrate on the role of this cell type in the making
      of a tolerant CD4 T cell repertoire and in the sustenance of CD4 T cell responses
      for protective immunity.

PMID- 20800821
TI  - Commentary on "lymphoid tissue inducer cells and the evolution of CD4 dependent
      high-affinity antibody responses".

PMID- 20800822
TI  - Cellular and molecular requirements in lymph node and Peyer's patch development.
AB  - Lymphoid tissues have a unique role in the organization and function of the
      adaptive immune system. Mechanisms driving the development of these tissues have
      fascinated immunologists for the last 175 years. In this review, we will
      initially focus on historical literature describing lymph node (LN) anlage
      development and then on the contemporary understanding of the molecular
      mechanisms driving LN and Peyer's patch (PP) formation. Utilizing transgenic
      reporters and gene knockout mice, the interplay between hematopoietic inducer
      cells and stromal organizer cells has been shown to have a key role in the
      development and organization of the lymphoid tissues. Although PPs and LNs share
      many similarities in their development, key differences in the molecular
      requirements for their development have recently emerged.

PMID- 20800823
TI  - T follicular helper cells during immunity and tolerance.
AB  - Helper T cells are required for the generation of a potent immune response to
      foreign antigens. Amongst them, T follicular helper (Tfh) cells are specialized
      in promoting protective, long-lived antibody responses that arise from germinal
      centers. Within these structures, the specificity of B cell receptors may change,
      due to the process of random somatic hypermutation aimed at increasing the
      overall affinity of the antibody response. The danger of emerging self-reactive
      specificities is offset by a stringent selection mechanism delegated in great
      part to Tfh cells. Only those B cells receiving survival signals from Tfh cells
      can exit the germinal centers to join the long-lived pools of memory B cells and
      bone marrow-homing plasma cells. Thus, a crucial immune tolerance checkpoint to
      prevent long-term autoantibody production lies in the ability to tolerize Tfh
      cells and to control positive and negative selection signals delivered by this
      subset. This review tackles the known mechanisms that ensure Tfh tolerance, many
      of them shared by other T helper subsets during thymic development and priming,
      but others unique to Tfh cells. Amongst the latter are checkpoints at the stages
      of Tfh differentiation, follicular migration, growth, longevity, and quality
      control of selection signals. Finally, we also discuss the consequences of a
      breakdown in Tfh tolerance.

PMID- 20800824
TI  - Thymic selection and lineage commitment of CD4(+)Foxp3(+) regulatory T
      lymphocytes.
AB  - Regulatory T lymphocytes play a central role in the control of a variety of
      immune-responses. Their absence in humans and in experimental animal models leads
      to severe autoimmune and inflammatory disorders. Consistent with their major role
      in prevention of autoimmune pathology, their repertoire is enriched in
      autospecific cells. Probably the majority of regulatory T cells develop in the
      thymus. How T cell-precursors choose between the conventional versus regulatory T
      cell lineages remains an unanswered question. More is known about selection of
      regulatory T cell precursors. Positive selection of these cells is favored by
      high affinity interactions with MHC class II/peptide ligands expressed by thymic
      epithelial or dendritic cells. They are also known to be relatively resistant to
      negative selection. These two parameters allow for the generation of the
      autoreactive regulatory T cell repertoire, and clearly distinguish selection
      criteria of conventional versus regulatory T cell-precursors. It will now be
      important to elucidate the molecular mechanisms involved in the intrathymic
      choice of the regulatory T cell-lineage.

PMID- 20800825
TI  - Molecular mechanisms of regulatory T cell development and suppressive function.
AB  - The requirement for regulatory T cells (Treg) to maintain tolerance to self
      tissues is evidenced by fatal autoimmune disease that results from genetic
      deficiencies in Treg cell development or Treg cell depletion in vivo. These
      observations revealed that a normal T cell repertoire harbors self-reactive T
      cells that are kept dormant by Treg cells. In order to prevent auto-reactive T
      cell activation, Treg cells disarm antigen-presenting cells (APC) through
      multiple suppressive mechanisms including B7 signaling and sequestration, ATP
      catabolism, cytolysis, and immunosuppressive cytokine secretion. In addition to
      APCs, multiple leukocyte subsets are subjected to Treg cell mediated suppression.
      The acquisition of suppressive activity occurs concomitantly with Treg cell
      lineage commitment. The identification of molecular cues that guide
      differentiation of Treg cells versus auto-reactive cells or other CD4(+) T cell
      subsets have been aided by the differential expression of the transcription
      factor Foxp3 by Treg cells. Foxp3 is the most faithful marker for Treg cells and
      in its absence, Treg cell development is abrogated. Utilizing Foxp3 expression as
      a surrogate for Treg cell commitment, factors that promote Foxp3 transcription
      have provided new insights to Treg cell development at a molecular level.

PMID- 20800826
TI  - Is foxp3 the master regulator of regulatory T cells?

PMID- 20800827
TI  - Parallel patterns of spatial compatibility and spatial congruence...as long as
      you don't look too closely.
AB  - The effects of spatial compatibility and spatial congruence have both been
      explained in terms of a dual-route model under which spatial information about
      the stimulus, regardless of task relevance, is directly passed from perception to
      action. Recently, however, some alternatives to the dual-route model of the Simon
      Effect have been proposed (or re-introduced) as viable explanations. The present
      experiment compared the magnitudes of the effects of spatial compatibility and
      spatial congruence across a range of tasks that varied in their dimensional
      overlap. The results exhibited a remarkable parallel between the two phenomena
      when viewed only in terms of the interaction between stimulus set and response
      set. This could be taken as new evidence for a common origin. However, when the
      entire pattern of results was examined, a large difference between compatibility
      and congruence were also seen, which implies that there is at least one important
      difference between the two phenomena.

PMID- 20800828
TI  - Oral contraceptives vs injectable progestin in their effect on sexual behavior.
AB  - OBJECTIVE: We sought to compare sexual function and hormone concentrations in
      combined oral contraceptive (COC) and injectable progestin users. STUDY DESIGN:
      Sexually active COC and depot medroxyprogesterone acetate (DMPA) users completed
      the Female Sexual Function Index (FSFI) questionnaire, a demographic data form,
      and had serum testosterone and estradiol levels measured. Multiple linear
      regression was used to measure associations of interest. RESULTS: Among 50
      subjects enrolled, COC users had lower levels of free testosterone compared to
      DMPA users (0.2 vs 0.6 pg/mL; P < .0001) and higher levels of estradiol (75.8 vs
      62.8 pg/mL; P = .0057), but scores of desire (4.2 vs 3.8; P = .27), scores of
      arousal (5.0 vs 4.8; P = .46), or total scores (30.1 vs 28.8; P = .28) were no
      different. Demographic characteristics were similar except for ethnicity, level
      of education, gravidity, parity, and frequency of intercourse. In multivariate
      analysis, birth control type was not significantly associated with desire score
      or total FSFI score. CONCLUSION: While users of COC and DMPA have significantly
      different sex hormone levels, they are not different in sexual function as
      measured by the FSFI.

PMID- 20800829
TI  - [Inflammasome and cardiovascular diseases].
AB  - NOD-like receptors (NLRs) constitute a recently identified family of
      intracellular pattern recognition receptors which contains more than 20 members
      in mammals. Some of the NLRs, the NALP subfamily, constituted from 14 members,
      many of them without actual identified role, form multiproteic complex known as
      inflammasome, that initiate inflammation by processing inactive pro-caspase-1 to
      its active form, allowing the cleavage and subsequent activation of pro-IL-1beta
      and pro-IL-18. We review the identified roles of NLRs in pathologies and argue
      for the role of inflammasome in the development of cardiovascular diseases. The
      atherogenic cytokines IL-1beta and IL-18 are matured in NLRPs inflammasomes.
      Immunocytochemistry shows that Nlrp3 inflammasome is expressed in plaques,
      upregulated and activated in the CD11b(+)Gr1(high) atherosclerosis-prone monocyte
      subset and modulated by oxLDL in murine macrophages. These results provide an
      unexpected role for Nlrp3 inflammasome in atherosclerosis.

PMID- 20800830
TI  - MUC1 and the simple mucin-type antigens: Tn and Sialyl-Tn are differently
      expressed in salivary gland acini and ducts from the submandibular gland, the
      vestibular folds, and the soft palate.
AB  - OBJECTIVE AND DESIGN: Autopsies of the submandibular gland, the vestibular folds
      and the soft palate from 65-87 old humans were examined to record the
      immunohistochemical expression of MUC1 and the simple mucin-type antigens Tn and
      Sialyl-Tn. RESULTS: (1) The serous acini in the submucosal glands from the larynx
      and the soft palate expressed MUC1-associated glycans that were not detectable in
      the serous acini from the submandibular gland. (2) Virtually all the submucosal
      acini at oral site of the soft palate are mucous, and in contrast to mucous acini
      in the vestibular folds and submandibular gland, the palatinal acini in the
      submucosa underneath the oral mucosa showed a well-defined cytoplasmic reaction
      with anti-MUC1 antibodies as wells as with anti-Tn. (3) Both the mucous acini and
      the ducts at the oral site of the soft palate showed reaction for Sialyl-Tn while
      in the vestibular folds and in the submandibular gland expression for this
      carbohydrate was observed only in the acini. (4) The staining obtained after
      incubation with the Tn antibodies showed no cross localization with the staining
      obtained after incubation with an anti-A blood group antibody. (5) All the
      autopsies showed reaction in the glands after incubation with the MUC1 antibodies
      while some autopsies reacted with the anti-Tn antibodies and/or with the anti
      Sialyl-Tn antibodies and others did not. CONCLUSION: The mucin expression in the
      acini and ducts from the upper human aerodigestive tract strongly depended on the
      location of the glandular tissue.

PMID- 20800831
TI  - No evidence for a prolonged attentional blink in developmental dyslexia.
AB  - When two targets are presented within 500 msec of each other in rapid serial
      visual presentation (RSVP), the accuracy of second target identification is
      significantly reduced; a phenomenon termed the attentional blink. Recent studies
      have reported that children and adults with dyslexia exhibit deficits tied to the
      attentional blink; however, some ambiguity remains as to the nature of these
      impairments and how they relate to reading difficulties. The current study aimed
      to address these issues by examining attentional blink deficits in relation to
      orthographic, phonological, and fluency aspects of reading impairment. Twenty-two
      children with dyslexia were compared to 22 children with normally developing
      reading skills on an attentional blink task with results indicating the dyslexia
      group exhibited impaired performance regardless of the temporal lag between
      targets. These deficits appeared tied to general RSVP performance rather than a
      prolonged attentional blink and differences between groups fell below
      significance when the influence of general performance factors were controlled
      for.

PMID- 20800832
TI  - Prenatal exposure to PFOA and PFOS and risk of hospitalization for infectious
      diseases in early childhood.
AB  - OBJECTIVES: To examine whether prenatal exposure to perfluorooctanesulfonate
      (PFOS) or perfluorooctanoate (PFOA) is associated with the occurrence of
      hospitalization for infectious diseases during early childhood. METHODS: We
      randomly selected 1400 pregnant women and their offspring from the Danish
      National Birth Cohort (1996-2002) and measured PFOS and PFOA levels in maternal
      blood during early pregnancy. Hospitalizations for infection of the offspring
      were identified by the linkage to the National Hospital Discharge Register
      through 2008. RESULTS: Hospitalizations due to infections were not associated
      with prenatal exposure to PFOA and PFOS. On the contrary, the relative risks of
      hospitalizations ranged from 0.71 to 0.84 for the three higher quartiles of
      maternal PFOA levels compared with the lowest, but no dose-response pattern was
      found. No clear pattern was observed when results were stratified by child's age
      at infection, with the exception of an inverse association between maternal PFC
      levels and risk of hospitalization during the child's first year of life.
      CONCLUSIONS: These findings suggest that prenatal exposure to PFOA or PFOS is not
      associated with increased risk of infectious diseases leading to hospitalization
      in early childhood.

PMID- 20800833
TI  - Evaluation of endometrial biomarkers for semi-invasive diagnosis of
      endometriosis.
AB  - OBJECTIVE: To test the hypothesis that specific proteins and peptides are
      expressed differentially in eutopic endometrium of women with and without
      endometriosis and at specific stages of the disease (minimal, mild, moderate, or
      severe) during the secretory phase. DESIGN: Patients with endometriosis were
      compared with controls. SETTING: University hospital. PATIENT(S): A total of 29
      patients during the secretory phase were selected for this study on the basis of
      cycle phase and presence or absence of endometriosis. INTERVENTION(S):
      Endometriosis was confirmed laparoscopically and histologically in 19 patients
      with endometriosis of revised American Society for Reproductive Medicine stages
      (9 minimal-mild and 10 moderate-severe), and the presence of a normal pelvis was
      documented by laparoscopy in 10 controls. MAIN OUTCOME MEASURE(S): Protein
      expression of endometrium was evaluated with use of surface-enhanced laser
      desorption/ionization time-of-flight mass spectrometry. The differential
      expression of protein mass peaks was analyzed with use of support vector machine
      algorithms and logistic regression models. RESULT(S): Data preprocessing resulted
      in differential expression of 73, 30, and 131 mass peaks between controls and
      patients with endometriosis (all stages), with minimal-mild endometriosis, and
      with moderate-severe endometriosis, respectively. Endometriosis was diagnosed
      with high sensitivity (89.5%) and specificity (90%) with use of five down
      regulated mass peaks (1.949 kDa, 5.183 kDa, 8.650 kDa, 8.659 kDa, and 13.910 kDa)
      obtained after support vector machine ranking and logistic regression
      classification. With use of a similar analysis, minimal-mild endometriosis was
      diagnosed with four mass peaks (two up-regulated: 35.956 kDa and 90.675 kDa and
      two down-regulated: 1.924 kDa and 2.504 kDa) with maximal sensitivity (100%) and
      specificity (100%). The 90.675-kDa and 35.956-kDa mass peaks were identified as T
      plastin and annexin V, respectively. CONCLUSION(S): Surface-enhanced laser
      desorption/ionization time-of-flight mass spectrometry analysis of secretory
      phase endometrium combined with bioinformatics puts forward a prospective panel
      of potential biomarkers with sensitivity of 100% and specificity of 100% for the
      diagnosis of minimal to mild endometriosis.

PMID- 20800834
TI  - Periodontal disease in polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) and periodontal disease (inflammatory diseases
      of the tissues around teeth) are common disorders associated with diabetes and
      cardiometabolic risk. Comprehensively examining the periodontal status in PCOS,
      this study suggests that the susceptibility for periodontal disease may
      significantly increase in patients with PCOS compared with healthy young women,
      and that local/periodontal oxidant status appears to be affected in PCOS.

PMID- 20800835
TI  - Operational space trajectory tracking control of robot manipulators endowed with
      a primary controller of synthetic joint velocity.
AB  - In this paper, a new control algorithm for operational space trajectory tracking
      control of robot arms is introduced. The new algorithm does not require velocity
      measurement and is based on (1) a primary controller which incorporates an
      algorithm to obtain synthesized velocity from joint position measurements and (2)
      a secondary controller which computes the desired joint acceleration and velocity
      required to achieve operational space motion control. The theory of singularly
      perturbed systems is crucial for the analysis of the closed-loop system
      trajectories. In addition, the practical viability of the proposed algorithm is
      explored through real-time experiments in a two degrees-of-freedom horizontal
      planar direct-drive arm.

PMID- 20800836
TI  - Sexual dysfunction among women of low-income status in an urban setting.
AB  - OBJECTIVE: To determine demographic and clinical conditions associated with
      sexual dysfunction among women of low-income status living in an urban setting.
      METHODS: Cross-sectional study of 102 consecutive women attending an urban
      gynecology clinic. Women were given validated questionnaires to measure sexual
      function, depression, urinary incontinence, and erectile dysfunction in the
      partner. The association of sexual dysfunction with demographic variables,
      depression, urinary incontinence, and sexual function in the partner was assessed
      by the respondent. RESULTS: The prevalence of sexual dysfunction was 37.3%
      (n=38). Women with sexual dysfunction reported significantly lower scores on all
      subscales of sexual function compared with women without sexual dysfunction.
      Women with sexual dysfunction were more likely to be older (33+/-11.2 vs 28.7+/
      8.6; P<0.04), unemployed (68% vs 47%; P<0.03), and report depression (OR 4.4; 95%
      CI, 1.7-11.3), urinary urge incontinence (OR 2.7; 95% CI, 1.2-7.3), and intake of
      multiple medications (OR 5.4; 95% CI, 1.6-20.1). On multivariate analysis,
      depression and urge urinary incontinence were independently associated with
      sexual dysfunction. CONCLUSION: Female sexual dysfunction is associated with the
      presence of depression and urge urinary incontinence in women of low-income
      status living in an urban setting.

PMID- 20800837
TI  - Adolescent pregnancy outcomes and risk factors in Malaysia.
AB  - OBJECTIVE: To assess the outcomes and risk factors of adolescent pregnancies in 2
      major hospitals in Malaysia. METHODS: We conducted a case-control study of
      pregnant girls aged 10 through 19 years. The controls were women aged 20 through
      35 years who did not become pregnant in their adolescence. Cases and controls
      were matched for parity and place of delivery. Data were collected from
      questionnaires and the hospitals' medical records. RESULTS: The study included
      102 cases and 102 controls. There were significant associations between
      adolescent pregnancy and low education level, low socioeconomic status, being
      raised by a single parent, not engaging in extracurricular school activities,
      engaging in unsupervised activities with peers after school, and substance abuse
      (P<0.05 for all); being anemic, being unsure of the expected delivery date, and
      having few antenatal visits and a late delivery booking; and low Apgar scores and
      perinatal complications. CONCLUSION: Adolescent pregnancies are high-risk
      pregnancies. Better sexual health strategies are required to address the
      associated complications.

PMID- 20800838
TI  - Long-term follow-up of a comprehensive HIV and sexually transmitted infection
      prevention program for female sex workers in Ningbo, China.

PMID- 20800839
TI  - Effect of married women's beliefs about gender equity on their use of prenatal
      and delivery care in rural China.
AB  - OBJECTIVE: To investigate the effect of married women's beliefs regarding gender
      equity on their use of prenatal and delivery care in China's rural Xinjiang and
      Anhui provinces. METHODS: In this survey, 1029 women aged from 15 to 69 years,
      living in rural Xinjiang and Anhui provinces, and married, answered a
      questionnaire designed to collect information on their demographic
      characteristics, reproductive history (number of pregnancies, level of prenatal
      care, and mode and place of delivery), and beliefs regarding gender equity. We
      quantified "belief in gender equity" based on responses to 7 specific statements
      and graded the responses according to a system scoring the strength of the
      overall belief (a total score >=19, strong; 15-18, moderate; and <=14, weak).
      RESULTS: Only 34.3% of the women demonstrated strong convictions about gender
      equity. Even after adjusting for education and ethnicity, the percentage of women
      who received consistent prenatal care and were delivered at a maternity facility
      was highest among those scoring 19 or higher, and the reverse was true for women
      scoring 14 or less. CONCLUSION: Overall, women in China's rural Xinjiang and
      Anhui provinces do not hold strong convictions about gender equity. There was a
      positive correlation between belief in gender equity and use of prenatal and
      delivery care.

PMID- 20800840
TI  - Comparison of the effects of episiotomy and no episiotomy on pain, urinary
      incontinence, and sexual function 3 months postpartum: a prospective follow-up
      study.
AB  - BACKGROUND: The episiotomy rate has declined worldwide but remains high in
      several countries such as Taiwan. The effects of episiotomy on women's health
      should be a constant concern. Few data are available on the effect of episiotomy
      by validated measures. OBJECTIVE: The present study examined the effect of
      episiotomy on pain, urinary incontinence, and sexual function up to 3 months
      postpartum. DESIGN, SETTING AND PARTICIPANTS: A prospective follow-up study of
      243 women who completed the Taiwanese versions of the Short Form McGill Pain
      Questionnaire, International Consultation on Incontinence Questionnaire - Urinary
      Incontinence Short Form, Female Sexual Function Index, and a demographic
      questionnaire after vaginal delivery in a Taiwanese medical center. METHODS:
      Differences between those who did and did not have an episiotomy were tested
      using ANCOVA, adjusting for age, parity, newborn weight, and vacuum delivery. The
      reliability and validity of the measuring instruments were assessed using
      Cronbach's alpha coefficient and factor analysis. RESULTS: Women who delivered
      without an episiotomy had significantly lower perineal pain scores at weeks 1, 2
      and 6 postpartum compared to women who had an episiotomy (p=0.0065, 0.0391,
      0.0497, respectively). Women in the no-episiotomy group had significantly lower
      non-localized pain scores at week 2 postpartum compared to women in the
      episiotomy group (p=0.0438). The mean urinary incontinence score was
      significantly higher in the episiotomy group 3 months postpartum (p=0.0293). No
      significant difference in sexual function score was found between groups.
      CONCLUSIONS: The results indicate that episiotomy increased pain at weeks 1, 2
      and 6 postpartum, and urinary incontinence at 3 months postpartum. Awareness of
      the relationship between episiotomy and women's health will help health care
      professionals develop policy and promote the application of restrictive
      episiotomy.

PMID- 20800841
TI  - A novel method of studying fascicle architecture in relaxed and contracted
      muscles.
AB  - A muscle's architecture, described by geometric variables such as fascicle
      pennation angles or lengths, plays a crucial role in its functionality. Usually,
      single parameters are used to estimate force vectors or lengthening rates,
      thereby assuming that they represent the architecture properly and are constant
      during contraction. To describe muscle architecture in more detail and compare
      relaxed and contracted states, we developed and validated a new approach. The m.
      soleus of the laboratory rat was shock-frozen while relaxed and under isometric
      contraction, reconstructed three-dimensionally from histological sections, and
      fascicle lengths, curvatures and pennation angles, as well as the shape of the
      aponeuroses were analysed. Remarkable differences in volume distribution and the
      shapes of the aponeuroses as well as locally varying changes in the fascicle
      architecture were observed. While the mean pennation angle increased by only 2
      degrees  due to contraction, local changes of up to 4 degrees  were observed.
      Fascicle curvature increased in the distal but remained unchanged in the proximal
      parts. Our approach may help to identify functional subunits within the muscle,
      i.e., regions with homogeneous architectural properties. Our results are
      discussed regarding the input parameters essential for realistic muscle modelling
      and challenge maximum isometric force estimations that are based on the
      physiological cross-sectional area or the Hill-model.

PMID- 20800842
TI  - Mechanical skin thinning-to-thickening transition observed in vivo through 2D
      high frequency elastography.
AB  - This study was based on two dimensional (2D) high frequency elastography to
      describe quantitatively the mechanical behavior of the human dermis in vivo. The
      study was conducted on the forearm skin and elastographic tests were performed
      using a combination of two devices: an extensiometer developed for the in vivo
      study of the mechanical behavior of the skin using uniaxial stretching stress,
      and a 20MHz real time sonographer (Dermcup 2020TM) for ultrasound skin imaging.
      The staggered strain estimation algorithm (SSE) was used to produce elastograms.
      A temporal cumulative technique was applied to improve elastogram quality and to
      monitor variations in skin strain during stretching. The influence of the natural
      skin tension controlled by arm bending was studied and distinctive mechanical
      behavior was observed for low and high mechanical stress levels. In a preliminary
      analysis, the reproducibility of measurements was assessed by means of
      coefficient of variation (CV) in 5 selected healthy volunteers.Finally, two
      hypotheses linked to the geometrical and structural properties of the dermis are
      proposed to account for the new findings described in this study.

PMID- 20800843
TI  - A motion-decomposition approach to address gimbal lock in the 3-cylinder open
      chain mechanism description of a joint coordinate system at the glenohumeral
      joint.
AB  - In this study, the standard-sequence properties of a joint coordinate system were
      implemented for the glenohumeral joint by the use of a set of instantaneous
      geometrical planes. These are: a plane that is bound by the humeral long axis and
      an orthogonal axis that is the cross product of the scapular anterior axis and
      this long axis, and a plane that is bounded by the long axis of the humerus and
      the cross product of the scapular lateral axis and this long axis. The relevant
      axes are updated after every decomposition of a motion component of a humeral
      position. Flexion, abduction and rotation are then implemented upon three of
      these axes and are applied in a step-wise uncoupling of an acquired humeral
      motion to extract the joint coordinate system angles. This technique was
      numerically applied to physiological kinematics data from the literature to
      convert them to the joint coordinate system and to visually reconstruct the
      motion on a set of glenohumeral bones for validation.

PMID- 20800844
TI  - Solvent effects on the retention of oligosaccharides in porous graphitic carbon
      liquid chromatography.
AB  - Porous graphitic carbon (PGC) is known as well suited adsorbent for liquid
      chromatography of carbohydrates. In this work we report on systematic
      investigations of solvent effects on the retention mechanism of fluorescence
      labeled malto-oligosaccharides on PGC. The adsorption mechanism was found to
      depend on the type of organic modifier used in the mobile phase. Positive
      adsorption enthalpies and entropies, which have already been reported in the
      literature, were solely produced using acetonitrile. Both alternative solvents
      (tetrahydrofuran, 2-propanol) yielded in contrast negative enthalpies. As
      plausible retention mechanism for oligosaccharides on PGC applying acetonitrile
      as mobile phase component we propose the formation of a dense and highly ordered
      solvation layer of the PGC surface with the linear acetonitrile molecules.
      Adsorption of analyte molecules requires a displacement of numerous acetonitrile
      molecules, which explains the positive enthalpy and entropy values measured. The
      interplay of enthalpic and entropic contributions to the overall adsorption
      phenomena results in strongly temperature dependent chromatographic selectivity
      values.

PMID- 20800845
TI  - Analysis of phenylpiperazine-like stimulants in human hair as trimethylsilyl
      derivatives by gas chromatography-mass spectrometry.
AB  - A simple and sensitive procedure, using p-tolylpiperazine (pTP) as internal
      standard (IS), has been developed and validated for the qualitative and
      quantitative analysis of 1-(3-trifuoromethylphenyl)piperazine (TFMPP), 1-(3
      chlorophenyl)piperazine (mCPP) and 1-(4-methoxyphenyl)piperazine (MeOPP) in hair.
      Drug extraction was performed by incubation with 1 M sodium hydroxide at 50
      degrees C for 40 min, and the extracts were cleaned up using mixed-mode solid
      phase extraction. The analytes were derivatized with N-methyl-N-(trimethylsilyl)
      trifluoroacetamide with 5% trimethylchlorosilane and analysed by gas
      chromatography-mass spectrometry in the selected ion monitoring mode. The method
      was linear from 0.05 (lower limit of quantitation) to 4 ng mg(-1), with
      correlation coefficients higher than 0.99 for all the compounds. Intra- and
      interday precision and accuracy were in conformity with the criteria normally
      accepted in bioanalytical method validation, and the sample cleanup step
      presented a mean efficiency higher than 90% for all the analytes. Due to its
      simplicity and speed, this method can be successfully applied in the screening
      and quantitation of these compounds in hair samples, and is suitable for
      application in forensic toxicology routine analysis.

PMID- 20800846
TI  - Controlled fabrication and characterization of microspherical FeCO3 and alpha
      Fe2O3.
AB  - In this paper, the microspherical Fe(2)O(3) was successfully obtained by
      calcining the FeCO(3) sphere prepared by a hydrothermal route. The sphere
      morphology perfectly remained after the calcination of FeCO(3) but the diameter
      of sphere decreased in a certain degree from 70-100 MUm to 50-70 MUm, which might
      be due to some loss of quantity during the calcination (FeCO(3)-Fe(2)O(3)). The
      sphere was solid and highly densified. At the same time, the effects of factors
      influencing the formation of FeCO(3), such as PVP, reaction temperature were
      investigated. The simple formation process of FeCO(3) was also proposed as
      follows: Fe(2+) produced by the reduction of Fe(3+) reacted with CO(3)(2-)
      released from the decomposition of urea to form FeCO(3) nanoparticle. Then, the
      formed nanoparticles aggregated together to produce sphere structure via oriented
      attachment. With the reaction time increasing, the sphere became solidness and
      densification.

PMID- 20800847
TI  - A competitive aggregation model for flash nanoprecipitation.
AB  - Flash NanoPrecipitation (FNP) is a novel approach for producing functional
      nanoparticles stabilized by amphiphilic block copolymers. FNP involves the rapid
      mixing of a hydrophobic active (organic) and an amphiphilic di-block copolymer
      with a non-solvent (water) and subsequent co-precipitation of nanoparticles
      composed of both the organic and copolymer. During this process, the particle
      size distribution (PSD) is frozen and stabilized by the hydrophilic portion of
      the amphiphilic di-block copolymer residing on the particle surface. That is, the
      particle growth is kinetically arrested and thus a narrow PSD can be attained. To
      model the co-precipitation process, a bivariate population balance equation (PBE)
      has been formulated to account for the competitive aggregation of the organic and
      copolymer versus pure organic-organic or copolymer-copolymer aggregation.
      Aggregation rate kernels have been derived to account for the major aggregation
      events: free coupling, unimer insertion, and aggregate fusion. The resulting PBE
      is solved both by direct integration and by using the conditional quadrature
      method of moments (CQMOM). By solving the competitive aggregation model under
      well-mixed conditions, it is demonstrated that the PSD is controlled primarily by
      the copolymer-copolymer aggregation process and that the energy barrier to
      aggregate fusion plays a key role in determining the PSD. It is also shown that
      the characteristic aggregation times are smaller than the turbulent mixing time
      so that the FNP process is always mixing limited.

PMID- 20800848
TI  - Evaporation-induced self assembly of nanoparticles in non-buckling regime: volume
      fraction dependent packing.
AB  - Hierarchically structured micrometric spheres are synthesized by evaporation
      induced self assembly of silica colloids using spray drying technique. Packing of
      nanoparticles during drying of droplets is an important issue. The motivation of
      the present work is to investigate the effects of concentration of initial
      colloidal dispersion on the packing of the nanoparticles in assembled grains in
      non-buckling regime of drying. It has been observed that the packing of
      nanoparticles inside the dried grains, even in the non-buckling regime, varies
      significantly with concentration. Although, the packing of nanoparticles remains
      uniform in an assembled grain at smaller concentration, the same becomes non
      uniform at higher concentration. Further, the average packing fraction of the
      nanoparticles within the assembled grains, decreases with increasing colloidal
      concentration. These observations have been attributed to the modification in
      viscosity of the initial dispersion. Electron microscopy, light scattering
      measurements have been performed to probe overall morphology of the dried grains,
      while inter-particle correlation inside the grains has been investigated by small
      angle neutron scattering.

PMID- 20800849
TI  - Fabrication of silver nanoparticles/single-walled carbon nanotubes composite for
      surface-enhanced Raman scattering.
AB  - A simple method of the fabrication of silver nanoparticles/single-walled carbon
      nanotubes (Ag/SWNTs) composite for surface-enhanced Raman scattering was
      presented. The morphology of Ag/SWNTs composite was characterized by scanning
      electron microscopy and X-ray diffraction. The performance of the Ag/SWNTs
      composite as surface-enhanced Raman scattering (SERS) active substrate was
      evaluated via using 4-aminothiophenol (PATP) as the probe molecule. Compared with
      PATP on AgNPs film, the SERS signal of PATP was obviously improved on the
      Ag/SWNTs composite. Then, by examining the relative enhancement of the nontotally
      symmetric (b(2)) modes of PATP, this effect was shown to arise from a charge
      transfer contribution between molecule and metal.

PMID- 20800850
TI  - Effects of solid particle content on properties of o/w Pickering emulsions.
AB  - The control of droplet size and stability of oil-in-water Pickering emulsions
      stabilized by hydrophobized fumed silica was investigated. Three regimes were
      observed according to the silica content: instability at low silica content,
      stable emulsions with droplet size controlled by the silica content, and
      emulsions of constant size set by the emulsification process at high silica
      concentrations. The oil-to-silica ratio was the relevant parameter of the size
      control in the medium concentration regime. Centrifugation experiments and
      particle size distribution measurements gave evidence of the presence of excess
      silica present as dispersion in the aqueous phase in the high silica content
      regime. Adsorption of silica to the droplet surface did not follow adsorption
      equilibrium; strong adsorption prevailed. Lastly, aggregation of silica particles
      appeared a crucial parameter. Oil adsorption and capillary condensation of oil
      within the silica aggregates provided a supplementary mechanism of silica
      aggregation that contributed to the stability of emulsions.

PMID- 20800851
TI  - Plasmonic heating assisted deposition of bare Au nanoparticles on titania
      nanoshells.
AB  - A very simple procedure for depositing bare Au nanoparticles onto the surface of
      oxide nanoshells is presented. This method is based on plasmonic heating assisted
      processes which are triggered by a continuous wave laser source that is focused
      through the objective of a Raman microscope. The Au nanoparticles are obtained
      upon laser irradiation of colloidal crystals consisting of Au semishells buried
      in titania overlayers. SERS activity and heating effects induced by laser
      irradiation are demonstrated in a series of microRaman experiments.

PMID- 20800853
TI  - Organic pollutants in microplastics from two beaches of the Portuguese coast.
AB  - Microplastics pose a threat to coastal environments due to their capacity to
      adsorb persistent organic pollutants (POPs). These particles (less than 5 mm in
      size) are potentially dangerous to marine species due to magnification risk over
      the food chain. Samples were collected from two Portuguese beaches and sorted in
      four classes to relate the adsorption capacity of pollutants with color and age.
      Polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and
      DDTs were analysed on pellets through gas chromatography mass spectrometry (GC
      MS), and types of plastic were identified using Fourier transformed infra-red
      spectroscopy (micro-FTIR). Microplastics were mostly polyethylene and
      polypropylene. Regarding sizes, some fibres ranged from 1 to 5 MUm in diameter
      and were 500 MUm in length. The majority of samples collected had sizes above 200
      MUm. Black pellets, unlike aged pellets, had the highest concentrations of POPs
      except for PAHs in Fonte da Telha beach. PAHs with higher concentrations were
      pyrene, phenantrene, chrysene and fluoranthene. Higher concentrations of PCBs
      were found for congeners 18, 31, 138 and 187. Further investigation is necessary
      to understand the relationship between plastic degradation and adsorption for
      different pollutants.

PMID- 20800852
TI  - Gambling problem severity and psychiatric disorders among Hispanic and white
      adults: findings from a nationally representative sample.
AB  - OBJECTIVE: To examine differences in the associations of gambling problem
      severity and psychiatric disorders among a nationally representative sample of
      Hispanic and white adults. METHOD: Chi-square tests and multinomial logistic
      regression analyses were performed on data obtained from the National
      Epidemiologic Survey on Alcohol and Related Conditions from 31,830 adult
      respondents (13% Hispanic; 87% white), who were categorized according to three
      levels of gambling problem severity (i.e., no gambling or low-frequency gambling
      [NG], low-risk or at-risk gambling [LRG], problem or pathological gambling
      [PPG]). RESULTS: Hispanic respondents in comparison to white respondents were
      more likely to exhibit PPG. Problem gambling severity was associated with past
      year Axis I and lifetime Axis II psychiatric disorders in both Hispanic and white
      respondents, with the largest odds typically observed in association with the
      most severe gambling pathology. A stronger relationship between subsyndromal
      gambling and a broad range of Axis I disorders (mood, anxiety and substance use
      disorders) and Axis II disorders (particularly cluster B) was observed in
      Hispanic respondents as compared to white ones. CONCLUSIONS: Levels of problem
      gambling severity are associated with the prevalence of Axis I and Axis II
      psychiatric disorders in both Hispanics and whites. Differences in the patterns
      of co-occurring disorders between subsyndromal levels of gambling in Hispanic and
      white respondents indicate the importance of considering ethnicity/race-related
      factors related to subthreshold levels of gambling in developing improved mental
      health prevention and treatment strategies.

PMID- 20800854
TI  - Chronic exposure of adults and embryos of Pandalus borealis to oil causes PAH
      accumulation, initiation of biomarker responses and an increase in larval
      mortality.
AB  - Adult shrimps (Pandalus borealis) and their embryos were exposed to an oil-water
      dispersion (OWD) at concentrations of 0.015, 0.06 and 0.25 mg/L using a
      continuous flow system. Lysosomal membrane stability was analysed in haemocytes
      using the neutral red retention assay and an alkaline unwinding assay was used to
      measure DNA damage in hepatopancreas tissue. Exposure to oil induced
      concentration and time dependent biomarker responses in adult shrimps together
      with the accumulation of PAH in their tissues. Oil exposure of shrimp embryos
      caused increased mortality in the resultant larvae, even if the larvae were kept
      in clean water after hatching. There were minor differences observed in larval
      stage development times in the first part of the experiments. The fatty acid
      composition of embryos exposed to oil was different to that of non-exposed
      larvae. PAH tissue concentration and biomarker responses correlated to the
      reduced survival of the shrimp larvae.

PMID- 20800855
TI  - Additive toxicity of herbicide mixtures and comparative sensitivity of tropical
      benthic microalgae.
AB  - Natural waters often contain complex mixtures of unknown contaminants potentially
      posing a threat to marine communities through chemical interactions. Here, acute
      effects of the photosystem II-inhibiting herbicides diuron, tebuthiuron,
      atrazine, simazine, and hexazinone, herbicide breakdown products (desethyl
      atrazine (DEA) and 3,4-dichloroaniline (3,4-DCA)) and binary mixtures, were
      investigated using three tropical benthic microalgae; Navicula sp. and
      Cylindrotheca closterium (Ochrophyta) and Nephroselmis pyriformis (Chlorophyta),
      and one standard test species, Phaeodactylum tricornutum (Ochrophyta), in a high
      throughput Maxi-Imaging-PAM bioassay (Maxi-IPAM). The order of toxicity was;
      diuron > hexazinone > tebuthiuron > atrazine > simazine > DEA > 3,4-DCA for all
      species. The tropical green alga N. pyriformis was up to 10-fold more sensitive
      than the diatoms tested here and reported for coral symbionts, and is recommended
      as a standard tropical test species for future research. All binary mixtures
      exhibited additive toxicity, and the use of herbicide equivalents (HEq) is
      therefore recommended in order to incorporate total-maximum-load measures for
      environmental regulatory purposes.

PMID- 20800856
TI  - Phenolamides: bridging polyamines to the phenolic metabolism.
AB  - Phenolamides constitute a diverse and quantitatively major group of secondary
      metabolites resulting from the conjugation of a phenolic moiety with polyamines
      or with deaminated aromatic aminoacids. This review summarizes their
      bioactivities and their reported roles in plant development, adaptation and
      defence compared to those of their polyamine precursors. The most conclusive
      recent developments point to their contribution to cell-wall reinforcement and to
      direct toxicity for predators and pathogens, either as built-in or inducible
      defence. Phenolamides were often considered as accumulated end-chain products.
      Recent data bring a light on their biosynthesis and suggests their possible
      contribution in the branching of the phenylpropanoid metabolism.

PMID- 20800858
TI  - Triterpenoidal saponins of Pulsatilla koreana roots.
AB  - Sixteen (1-16) triterpenoidal saponins were isolated from the roots of Pulsatilla
      koreana, of which four were determined as the previously unknown 23-hydroxy-3beta
      [(O-alpha-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid 28-O-beta-D
      glucopyranosyl ester (1), 23-hydroxy-3beta-[(O-alpha-L-rhamnopyranosyl-(1->2)
      alpha-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid 28-O-beta-D-glucopyranosyl
      ester (2), 3beta-[(O-alpha-L-rhamnopyranosyl-(1->2)-alpha-L
      arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid 28-O-beta-D-glucopyranosyl-(1->6)
      beta-D-glucopyranosyl ester (3), and 3beta-[(O-alpha-L-rhamnopyranosyl-(1->2)-O
      [beta-D-glucopyranosyl-(1->4)]-alpha-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic
      acid 28-O-alpha-L-rhamnopyranosyl-(1->4)-O-beta-D-glucopyranosyl-(1->6)-beta-D
      glucopyranosyl ester (4), respectively, based on spectroscopic analysis. The
      inhibition of the lipopolysaccharide-induced nitric oxide production of sixteen
      isolated compounds was evaluated in RAW 264.7 cells at concentrations ranging
      from 1 MUM to 100 MUM.

PMID- 20800857
TI  - Comparison of transcriptional profiles of flavonoid genes and anthocyanin
      contents during fruit development of two botanical forms of Fragaria chiloensis
      ssp. chiloensis.
AB  - Difference in fruit pigmentation observed between two botanical forms of Fragaria
      chiloensis ssp. chiloensis (form chiloensis and form patagonica) was studied
      through transcriptional and chemical approaches. The proportion of different
      anthocyanins was demonstrated to be characteristic of each botanical form, with
      pelargonidin 3-glucoside being the most abundant in f. patagonica fruit and
      cyaniding 3-glucoside as the major one in f. chiloensis fruit. Partial gene
      sequences of the phenylpropanoid and flavonoid biosynthesis pathways were
      isolated from the native Chilean strawberry fruits, and used to design gene
      specific primers in order to perform transcriptional analyses by qRT-PCR. These
      genes showed spatial, developmental, and genotypic associated patterns. The red
      fruit of f. patagonica exhibited higher transcript levels of anthocyanin-related
      genes and higher levels of anthocyanins compared to the barely pigmented fruit of
      f. chiloensis. The anthocyanin accumulation in F. chiloensis ssp. chiloensis
      fruits was concomitant with the particular progress of the transcriptional
      activity of genes involved in the biosynthesis of flavonoid pigments. The
      differences in anthocyanin contents, both in terms of type and quantity, between
      the two botanical forms of F. chiloensis ssp. chiloensis were coincident with the
      differential transcriptional patterns found in the anthocyanin-related genes.

PMID- 20800859
TI  - The effect of medetomidine on the regional cerebral blood flow in dogs measured
      using Technetium-99m-Ethyl Cysteinate Dimer SPECT.
AB  - Sedatives and anaesthetics are known to cause changes in the regional cerebral
      blood flow. In dogs intramuscular sedation with medetomidine, a potent sedative
      frequently used in veterinary medicine, is sometimes indicated prior to
      intravenous injection of (99m)Technetium-Ethyl Cysteinate Dimer ((99m)Tc-ECD) in
      brain perfusion studies using Single Photon Emission Computed Tomography (SPECT).
      Based on the knowledge of the distribution of alpha(2)-receptors in the brain, we
      hypothesized altered regional brain perfusion in dogs receiving medetomidine
      prior to (99m)Tc-ECD. Two conditions were compared in 10 dogs; tracer injection
      before and after intramuscular sedation with medetomidine. In our study,
      medetomidine caused a significantly higher tracer uptake in all brain regions.
      Semi-quantification of brain perfusion rendered a lower perfusion index in the
      subcortical region and an imbalance between left and right cortical perfusion
      induced by medetomidine. This study shows that caution is needed when quantifying
      the brain perfusion indices under medetomidine sedation.

PMID- 20800860
TI  - [Management of stroke in sub-Saharan Africa: current issues].
AB  - In sub-Saharan Africa, stroke is likely to present an increasingly important
      public health problem with a larger relative share of overall morbidity and
      mortality. Overall, sub-Saharan Health Care is characterized by a lack of human
      resources, lack of facilities for special investigations, and especially an
      absence of specific programs addressing the prevention of cardiovascular
      conditions. Current data on the epidemiology of stroke in sub-Saharan Africa,
      although sparse and fragmentary, indicate a comparatively high incidence of
      cerebral hemorrhage associated with high blood pressure, while ischemic stroke in
      black Africans still appears to be related primarily to small artery disease, HIV
      infection, and sickle cell disease. With urbanization, the role of large-vessel
      atherosclerosis is increasing. It is thus essential to coordinate government
      funding, health care professionals and development agencies to address this
      rising health problem. Access to health care needs to be better structured, and
      screening programs should be developed in order to identify and treat vascular
      risk factors. Improved training of health care professionals is also required in
      the areas of prevention, diagnosis and management of stroke. Implementation of
      best-practice recommendations for the management of stroke adapted to the
      specificities and resources of African countries would help rationalize the
      scarce resources currently available.

PMID- 20800861
TI  - Influence of haemoglobins S and C on predominantly asymptomatic Plasmodium
      infections in northern Ghana.
AB  - The haemoglobin (Hb) variants HbS and HbC protect against severe malaria. Yet,
      the influence particularly of HbC on asymptomatic or mild Plasmodium infection is
      not well established. In a dry season cross-sectional survey among 2108 children
      aged 0.5-9 years in the Northern Region of Ghana, Plasmodium species and density,
      as well as Hb, were analysed with respect to Hb genotypes. HbAC occurred in 19.7%
      and HbAS in 7.4% (HbSC, 0.8%; HbCC, 0.8%; HbSS, 0.3%). Overall, 56% of the
      children had microscopically visible parasitaemia. By PCR, P. falciparum, P.
      malariae, and P. ovale were present in 74.5%, 9.7%, and 5.5%, respectively.
      Febrile parasitaemia was rare (2.8%) but anaemia (Hb<11g/dL) frequent (59.3%).
      Children with HbAA and HbAC showed virtually identical malariometric parameters.
      In contrast, children with HbAS had significantly less parasitaemia, lower
      parasite densities, and a higher proportion of submicroscopic P. falciparum
      infection. Remarkably, in children with HbCC, P. malariae infection occurred in
      37.5% (adjusted odds ratio (aOR), 5.8; 95% CI, 1.8-18.8) and P. ovale in 18.8%
      (aOR, 3.61; 95% CI, 0.97-13.5). In this population with predominantly
      asymptomatic Plasmodium infection, HbAC shows no discernible effect on malaria
      related parameters. Homozygous HbC, in contrast, confers an increased risk of P.
      malariae infection which conceivably may modulate falciparum malaria.

PMID- 20800862
TI  - Surveillance after surgical treatment of melanoma: futility of routine chest
      radiography.
AB  - BACKGROUND: Current recommendations by the National Comprehensive Cancer Network
      and other groups suggest that follow-up of cutaneous melanoma may include chest
      radiography (CXR) at 6- to 12-month intervals. The aim of this study was to
      determine the clinical efficacy of routine CXR for recurrence surveillance in
      melanoma. METHODS: Post hoc analysis was performed on data from a prospective,
      randomized, multi-institutional study on melanoma >=1.0 mm in Breslow thickness.
      All patients underwent excision of the primary melanoma and sentinel node biopsy
      with completion lymphadenectomy for positive sentinel nodes. Yearly CXR and
      clinical assessments were obtained during follow-up. Results of routine CXR were
      compared with clinical disease states over the course of the study. RESULTS: A
      total of 1,235 patients were included in the analysis over a median follow-up of
      74 months (range, 12-138). Overall, 210 patients (17.0%) had a recurrence, most
      commonly local or in-transit. Review of CXR results showed that 4,218 CXR were
      obtained in 1,235 patients either before, or in the absence of, initial
      recurrence. To date, 88% (n = 3,722) CXR are associated with no evidence of
      recurrence. Of CXR associated with recurrence, only 7.7% (n = 38) of surveillance
      CXR were read as "abnormal." Overall, 99% (n = 4,180) of CXR were read as either
      "normal" or found to be falsely positive (read as "abnormal," but without
      evidence of recurrence on investigation). Only 0.9% (n = 38) of all CXR obtained
      were true positives ("abnormal" CXR, with confirmed first known recurrence).
      Among these 38 patients with true positive CXR, 35 revealed widely disseminated
      disease (multiorgan or bilateral pulmonary metastases); only 3 (0.2%) had
      isolated pulmonary metastases amenable to resection. Sensitivity and specificity
      for surveillance CXR in detecting initial recurrence were 7.7% and 96.5%,
      respectively. CONCLUSION: The routine use of surveillance CXR provides no
      clinically useful information in the follow-up of patients with melanoma. CXR
      does not detect recurrence at levels sufficient to justify its routine use and,
      therefore, cannot be recommended as part of the standard surveillance regimen for
      these patients.

PMID- 20800863
TI  - Parathyroidectomy for hypercalcemic crisis: 40 years' experience and long-term
      outcomes.
AB  - BACKGROUND: Hypercalcemic crisis is a serious and potentially life-threatening
      complication of markedly increased serum calcium concentrations most commonly due
      to severe primary sporadic hyperparathyroidism (HPT). METHODS: A review of 1,310
      consecutive patients with severe sporadic HPT who underwent parathyroidectomy at
      a single institution from April 1970 through July 2009 was performed. Of this
      series, 88 patients were treated operatively for hypercalcemic crisis associated
      with signs and symptoms of acute calcium intoxication and/or serum calcium
      concentrations >=14 mg/dL (3.5 mmol/L). Clinical presentation, laboratory values,
      operative success, operative failure, and disease recurrence were compared to
      noncrisis patients. RESULTS: Preoperative calcium and parathyroid hormone (PTH)
      concentrations were significantly greater among patients with hypercalcemic
      crisis. Crisis patients had a greater incidence of mental status changes,
      fatigue, ectopic glands, and pancreatitis. Postoperatively, calcium and PTH
      levels were similar. Overall, crisis patients had a lesser rate of operative
      success compared to noncrisis patients (92% vs 97%). With the advent of
      intraoperative PTH monitoring-guided focused parathyroidectomy in 1993, success
      rates equalized (95% vs 97%). There was no difference in disease recurrence.
      Overall follow-up was 59 months. CONCLUSION: Hypercalcemic crisis patients are
      appropriately treated by expeditious parathyroidectomy, but overall have slightly
      lesser rates of initial operative success than noncrisis patients. Long-term
      results reveal similar serum calcium, PTH concentrations, and recurrence rates at
      a mean follow-up of nearly 5 years.

PMID- 20800864
TI  - Impact of anastomotic leak on outcomes after transhiatal esophagectomy.
AB  - BACKGROUND: The development of anastomotic leaks and/or strictures can be
      associated with considerable morbidity and impairment of quality of life. In the
      current study, we evaluated the outcomes of patients who developed anastomotic
      complications after esophagectomy to elucidate the impact of these events on
      morbidity, mortality, and subsequent need for dilation. METHODS: We analyzed
      retrospectively the clinical course of 235 patients who underwent transhiatal
      esophagectomy for cancer from 2001 to 2009. Patients with confirmed anastomotic
      leaks were identified and classified with the following scale: class 1:
      Radiographic leak only, no intervention; class 2: leak requiring opening of the
      wound, cervical and/or percutaneous drainage; class 3: disruption of anastomosis
      (10-50% circumference) with perianastomotic abscess requiring video-assisted
      thoracoscopic surgery or thoracotomy; and class 4: gastric tip necrosis with
      anastomotic separation (>50% circumference). RESULTS: Anastomotic leaks were
      encountered in 30 patients (13%). Anastomotic leaks were associated with greater
      morbidity (70% vs 47%; P = .02) and stricture formation (57% vs 19%; P = .0001).
      Mortality was not different. Increasing leak class was associated with an
      increased need for postoperative anastomotic dilations (P = .016). CONCLUSION:
      Anastomotic integrity after esophagectomy has a substantial impact on
      perioperative course and long-term swallowing. A more formal radiographic and
      endoscopic leak classification system seems justified.

PMID- 20800865
TI  - FAST scan: is it worth doing in hemodynamically stable blunt trauma patients?
AB  - BACKGROUND: During the last decade, focused assessment with sonography for trauma
      increasingly has become the initial diagnostic modality of choice in trauma
      patients. It is still questionable, however, whether its use results in the
      underdiagnosis of intra-abdominal injury. It also remains doubtful whether a
      positive focused assessment with sonography for trauma affects clinical decision
      making in hemodynamically stable blunt trauma patients as evidenced through
      abdominal computerized tomography use. The aim of this study was to evaluate the
      results of focused assessment with sonography for trauma in hemodynamically
      stable blunt trauma patients and to determine its role in the diagnostic
      evaluation of these patients. METHODS: We reviewed our prospectively maintained
      trauma database. In trauma patients at our institute, focused assessment with
      sonography for trauma examinations are performed by surgery residents and are
      considered positive when free intra-abdominal fluid is visualized. Abdominal
      computerized tomography, diagnostic peritoneal lavage, or exploratory laparotomy
      findings were used as confirmation of intra-abdominal injury. RESULTS: In our 7
      year study period, 2,980 trauma patients were evaluated at our institute, of
      which 2,130 patients underwent a focused assessment with sonography for trauma.
      In all, 18 patients had an inconclusive focused assessment with sonography for
      trauma, whereas 7 patients died on arrival, leaving 2,105 patients for our
      analysis. A total 88 true positive focused assessment with sonography for trauma
      were conducted. All hemodynamically stable blunt trauma patients who had a
      positive focused assessment with sonography for trauma (70/88) were confirmed by
      computerized tomography. Patients who underwent exploratory laparotomy directly
      (17/88) or diagnostic peritoneal lavage (1/88) as confirmation either had
      penetrating trauma or became hemodynamically unstable. A total of 1,894 true
      negative focused assessments with sonography for trauma scans were conducted,
      with 1,201 confirmed by computerized tomography and the rest by observation. In
      all, 118 false negative focused assessment with sonography for trauma were
      performed, of which 44 (37.3%) subsequently required exploratory laparotomy. Five
      patients had false positive focused assessment with sonography for trauma scans.
      Focused assessment with sonography for trauma scan had an overall sensitivity of
      43%, a specificity of 99%, and positive and negative predictive values of 95% and
      94%, respectively. Accuracy was 94.1%. In the hemodynamically stable blunt trauma
      group, there were 60 patients with true positive focused assessment with
      sonography for trauma examinations and 87 patients with false negative focused
      assessment with sonography for trauma examinations. In this group of patients,
      focused assessment with sonography for trauma had a sensitivity of 41%,
      specificity of 99%, and positive and negative predictive values of 94% and 95%,
      respectively. The overall accuracy was 95%. CONCLUSION: Given the low
      sensitivity, a negative focused assessment with sonography for trauma without
      confirmation by computerized tomography may result in missed intra-abdominal
      injuries. It is also observed in all focused assessment with sonography for
      trauma positive hemodynamically stable blunt trauma patients, confirmation is
      preferred through the use of a computerized tomography for better understanding
      of the intra-abdominal injuries and to decide on operative versus no-operative
      management. Thus, the use of focused assessment with sonography for trauma in
      hemodynamically stable blunt trauma patients seems not worthwhile. It should be
      reserved for hemodynamically unstable patients with blunt trauma.

PMID- 20800866
TI  - A snake-based method for segmentation of intravascular ultrasound images and its
      in vivo validation.
AB  - Image segmentation for detection of vessel walls is necessary for quantitative
      assessment of vessel diseases by intravascular ultrasound. A new segmentation
      method based on gradient vector flow (GVF) snake model is proposed in this paper.
      The main characteristics of the proposed method include two aspects: one is that
      nonlinear filtering is performed on GVF field to reduce the critical points,
      change the morphological structure of the parallel curves and extend the capture
      range; the other is that balloon snake is combined with the model. Thus, the
      improved GVF and balloon snake can be automatically initialized and overcome the
      problem caused by local energy minima. Results of 20 in vivo cases validated the
      accuracy and stability of the segmentation method for intravascular ultrasound
      images.

PMID- 20800867
TI  - Effects of the interactions of classical swine fever virus Core protein with
      proteins of the SUMOylation pathway on virulence in swine.
AB  - Here we have identified host cell proteins involved with the cellular SUMOylation
      pathway, SUMO-1 (small ubiquitin-like modifier) and UBC9, a SUMO-1 conjugating
      enzyme that interact with classical swine fever virus (CSFV) Core protein. Five
      highly conserved lysine residues (K179, K180, K220, K221, and K246) within the
      CSFV Core were identified as putative SUMOylation sites. Analysis of these
      interactions showed that K179A, K180A, and K221A substitutions disrupt Core-SUMO
      1 binding, while K220A substitution precludes Core-UBC9 binding. In vivo, Core
      mutant viruses (K179A, K180A, K220A, K221A) and (K220A, K221A) harboring those
      substitutions were attenuated in swine. These data shows a clear correlation
      between the disruption of Core protein binding to SUMO-1 and UBC9 and CSFV
      attenuation. Overall, these data suggest that the interaction of Core with the
      cellular SUMOylation pathway plays a significant role in the CSFV growth cycle in
      vivo.

PMID- 20800868
TI  - Discovering microRNAs from Bombyx mori nucleopolyhedrosis virus.
AB  - MicroRNAs (miRNAs) have emerged as key players in host-pathogen interaction.
      Recently, many virus-encoded miRNAs have been identified from different mammalian
      species. However, the large family of invertebrate viruses of Baculoviridae,
      which infects diverse species of beneficial insects and agriculture pests, has
      hardly been investigated for elucidating the role of miRNAs in host-pathogen
      interaction. In the study reported here, we have identified four Bombyx mori
      nucleopolyhedrosis virus (BmNPV)-encoded miRNAs using a combination of in silico
      and experimental methods. Unlike other reported viral miRNAs, the BmNPV-encoded
      miRNAs identified in the present study were found to be evolutionarily conserved
      among many closely related baculoviruses. Besides, we have computationally
      predicted 8 viral and 64 cellular targets of these virus-encoded miRNAs and the
      putative functions of these targets suggest a key role of viral miRNAs in insect
      pathogen interactions by modulating several viral replication genes as well as
      those involved in host immune defense machinery.

PMID- 20800869
TI  - Optimization of performance assessment and design characteristics in constructed
      wetlands for the removal of organic matter.
AB  - Some of the most used constructed wetland (CW) configurations [conventional and
      modified free-water (FW) flow, surface flow, conventional horizontal subsurface
      flow (SSF) and soilless systems with floating macrophytes (FM)] were assessed in
      order to compare their efficiencies for the removal of organic pollutants [COD,
      filtered COD (FCOD), BOD and total suspended solids (TSS)] from urban sewage
      under the same climatic and wastewater conditions. The removal performance was
      calculated using three approaches: effluent concentrations, areal removed loads
      and mass removal. Results were very different depending on the approach, which
      indicates that the way to present CW efficiency should be considered carefully.
      All CW-configurations obtained BOD effluent concentrations below 25 mg L(-1) in
      summer, with a FW-CW with effluent leaving through the bottom of the tank being
      the only one maintaining low BOD effluent concentrations even in winter and under
      high organic loading conditions. In this kind of CW, the presence of plants
      favoured pollutant removal. SSF-CWs were the most efficient for the removal of
      COD. FM systems can be as efficient as some gravel bed CWs. Typhaangustifolia
      worked better than Phragmitesaustralis, at least when the systems were at the
      beginning of their operation period.

PMID- 20800870
TI  - Occurrence, distribution and origin of C30 cyclobotryococcenes in a subtropical
      wetland/estuarine ecosystem.
AB  - A series of C30 branched isoprenoid hydrocarbons with a cyclobotryococcane
      skeleton were identified in the Florida Coastal Everglades Ecosystem. Nine such
      C30 alkenes were detected and identified as five-membered ring monocyclic
      hydrocarbons with an identical parent structure of 7,11-cyclobotryococcane based
      on their mass spectra and hydrogenation behavior. Previous reports have suggested
      Botryococcus Braunii or green sulfur bacteria (Chlorobiaceae) as likely sources
      of these 7,11-cyclobotryococcanes. However, their enriched delta13C values (about
      -18%) determined in this study and their absence in freshwater marsh environments
      of the Everglades suggest that an origin from green sulfur bacteria or possibly
      marine diatoms is more likely. The depth profile of individual C30
      cyclobotryococcenes in one sediment core from Florida Bay shows abundant
      variations in their historical deposition and may indicate long-term changes of
      their source strength due to variations in local environmental conditions.

PMID- 20800871
TI  - Immunohistochemical analysis of NOTCH1 and JAGGED1 expression in multiple myeloma
      and monoclonal gammopathy of undetermined significance.
AB  - Notch signaling is implicated in the pathogenesis of multiple myeloma expressing
      high level of active Notch proteins NOTCH1 and JAGGED1 in tumor plasma cells. We
      investigated expression of NOTCH1 and JAGGED1 in bone marrow trephine biopsies of
      80 newly diagnosed multiple myeloma and 20 monoclonal gammopathy of undetermined
      significance patients using immunohistochemical methods. The number of positive
      tumor cells was counted per 1000 tumor cells and the intensity of staining was
      assessed semi quantitatively. Multiple myelomas expressed NOTCH1 in 92.31%
      (72/78) and JAGGED1 in 92.21% (71/77) cases. NOTCH1 staining was strong in the
      majority of cases (59.7%), whereas JAGGED1 was predominately weak (67.6% of
      cases). In contrast, both markers were negative in all monoclonal gammopathy of
      undetermined significance cases. However, upon progression of disease from
      monoclonal gammopathy of undetermined significance to multiple myeloma (seen in 4
      patients), analysis of the subsequent bone marrow biopsy showed weak expression
      of both markers in tumorous plasma cells. Immunohistochemistry results were
      compared with the pattern of bone marrow infiltration, plasma cell
      differentiation, and the presence of t(11;14)(q13,q32), t(14;16)(q32;q23),and
      t(4;14)(p16.3;q23) and overall survival in multiple myeloma patients. A
      significant correlation was found between strong NOTCH1 staining in multiple
      myeloma plasma cells and the diffuse type of bone marrow infiltration (P = .002)
      and an immature morphologic type of plasma cells (P = .043). After a median
      follow-up of 20.3 months, in multiple myeloma patients no difference in overall
      survival between NOTCH1 (P = .484) and JAGGED1 (P = .822) positive and negative
      cases were found. In conclusion, our results indicate importance of NOTCH1 and
      JAGGED1 expression in plasma cell neoplasia and a possible diagnostic value of
      their immunohistochemical evaluation of bone marrow infiltrates for multiple
      myeloma.

PMID- 20800872
TI  - Prognostic impact of CD133 expression as a tumor-initiating cell marker in
      endometrial cancer.
AB  - Tumor-initiating cells are known to be the major source of tumor propagation and
      might be an attractive therapeutic target. The present study dissected the roles
      of CD133 as a tumor-initiating cell marker in endometrial cancer and investigated
      the prognostic impact of this marker expression. Flow cytometry using 6
      endometrial cancer cell lines revealed that the frequency of CD133(+) cells
      varied widely among the cell types and that Ishikawa and MFE280 cells contained
      significantly higher ratio (10%-20%) of such cells; therefore, these were
      subjected to the subsequent analyses. Sorted CD133(+) cells showed more
      aggressive proliferative potential in vitro and more increased tumorigenicity in
      nude or NOD/SCID mice than CD133(-) cells and generated both CD133(+) and CD133(
      ) cells. Furthermore, they showed apparent resistance to cisplatin- or paclitaxel
      induced cytotoxicity compared with CD133(-) cells. CD133(+) cells had a greater S
      phase fraction than CD133(-) cells, and the serum starvation that induced G0/G1
      accumulation decreased the population of CD133(+) cells. Finally, we
      immunohistochemically analyzed the CD133 expression in endometrial cancer
      specimens from 62 patients. CD133 expression was not significantly associated
      with any of the clinicopathologic characteristic of tumors. However, the Kaplan
      Meier analysis revealed that tumors with high CD133 expression showed worse
      overall survival (P = .023, log-rank test) than those with low CD133 expression;
      and the Cox regression hazard model found that high CD133 expression was an
      independent prognostic factor (P = .045). Thus, the present study demonstrates
      that CD133 is not only a tumor-initiating cell marker but also a critical
      prognostic marker in endometrial cancer.

PMID- 20800873
TI  - Accumulation of metals in Elodea canadensis and Elodea nuttallii: implications
      for plant-macroinvertebrate interactions.
AB  - Elodea nuttallii and Elodea canadensis are considered good candidates for metal
      studies. Metal pollution can disturb the interactions between trophic levels. Our
      goals were 1) to analyse the metal content in plants, sediment and water from
      three polluted sites, and 2) to analyse the impact of metal contamination on
      plant consumption by macroinvertebrates. The concentrations of Cd, Cr, Cu, Mn,
      Ni, Pb, Zn and Fe and S were measured in water, sediment and in the two Elodea
      species during two years. Our results showed that metal accumulation varied
      according to site, metal and season. The ability to uptake metal was similar in
      E. canadensis and in E. nuttallii. No significant seasonal metal accumulation was
      established for plants or sediment. Metal accumulation in Elodea species in
      polluted sites had no impact on their palatability. The plant palatability
      depends on the season and varies according to the part of the plant. In autumn,
      apex was less consumed than defoliated and foliated stems.

PMID- 20800874
TI  - Exposure matrices of endotoxin, (1->3)-beta-d-glucan, fungi, and dust mite
      allergens in flood-affected homes of New Orleans.
AB  - This study examined: (i) biocontaminant levels in flooded homes of New Orleans
      two years after the flooding; (ii) seasonal changes in biocontaminant levels, and
      (iii) correlations between biocontaminant levels obtained by different
      environmental monitoring methods. Endotoxin, (1->3)-beta-d-glucan, fungal spores,
      and dust mite allergens were measured in 35 homes during summer and winter. A
      combination of dust sampling, aerosolization-based microbial source assessment,
      and long-term inhalable bioaerosol sampling aided in understanding exposure
      matrices. On average, endotoxin found in the aerosolized fraction accounted for
      <2% of that measured in the floor dust, suggesting that vacuuming could
      overestimate inhalation exposures. In contrast, the (1->3)-beta-d-glucan levels
      in the floor dust and aerosolized fractions were mostly comparable, and 25% of
      the homes showed aerosolizable levels even higher than the dust-borne levels. The
      seasonal patterns for endotoxin in dust and the aerosolizable fraction were
      different from those found for (1->3)-beta-d-glucan, reflecting the temperature
      and humidity effects on bacterial and fungal contamination. While the
      concentration of airborne endotoxin followed the same seasonal trend as endotoxin
      aerosolized from surfaces, no significant seasonal difference was identified for
      the concentrations of airborne (1->3)-beta-d-glucan and fungal spores. This was
      attributed to the difference in the particle size; smaller endotoxin-containing
      particles can remain airborne for longer time than larger fungal spores or (1->3)
      beta-d-glucan-containing particles. It is also possible that fungal
      aerosolization in home environments did not reach its full potential. Detectable
      dust mite allergens were found only in dust samples, and more commonly in
      occupied homes. Levels of endotoxin, (1->3)-beta-d-glucan, and fungi in air had
      decreased during the two-year period following the flooding as compared to
      immediate measurements; however, the dust-borne endotoxin and (1->3)-beta-d
      glucan levels remained elevated. No conclusive correlations were found between
      the three environmental monitoring methods. The findings support the use of
      multiple methods when assessing exposure to microbial contaminants.

PMID- 20800875
TI  - A screening of persistent organohalogenated contaminants in hair of East
      Greenland polar bears.
AB  - In this pilot study, we report on levels of persistent organohalogenated
      contaminants (OHCs) in hair of polar bears (Ursus maritimus) from East Greenland
      sampled between 1999 and 2001. To our knowledge, this is the first study on the
      validation of polar bear hair as a non-invasive matrix representative of
      concentrations and profiles in internal organs and blood plasma. Because of low
      sample weights (13-140mg), only major bioaccumulative OHCs were detected above
      the limit of quantification: five polychlorinated biphenyl (PCB) congeners (CB
      99, 138, 153, 170 and 180), one polybrominated diphenyl ether (PBDE) congener
      (BDE 47), oxychlordane, trans-nonachlor and beta-hexachlorocyclohexane. The PCB
      profile in hair was similar to that of internal tissues (i.e. adipose, liver,
      brain and blood), with CB 153 and 180 as the major congeners in all matrices. A
      gender difference was found for concentrations in hair relative to concentrations
      in internal tissues. Females (n=6) were found to display negative correlations,
      while males (n=5) showed positive correlations, although p-values were not found
      significant. These negative correlations in females may reflect seasonal OHC
      mobilisation from periphery adipose tissue due to, for example, lactation and
      fasting. The lack of significance in most correlations may be due to small sample
      sizes and seasonal variability of concentrations in soft tissues. Further
      research with larger sample weights and sizes is therefore necessary to draw more
      definitive conclusions on the usefulness of hair for biomonitoring OHCs in polar
      bears and other fur mammals.

PMID- 20800876
TI  - Integrated biological and chemical analysis of organochlorine compound pollution
      and of its biological effects in a riverine system downstream the discharge
      point.
AB  - Pollution in riverine systems, along with its biological effects, may propagate
      downstream even at considerable distances. We analyzed the organochlorine
      compound (OC) pollution in a section of the low Ebro River (Northeast Spain)
      downstream a long-operating chlor-alkali plant. Maximal levels of OCs and of
      their associated dioxin-like biological activity occurred in residue samples from
      the plant, and persisted in river sediments some 40km downstream (Xerta site).
      Biological analysis at multiple organization levels in local carp (Cyprinus
      carpio, EROD, Cyp1A mRNA expression in the liver, hepatosomatic index, condition
      factor, and micronuclei index in peripheral blood) showed a similar pattern, with
      a maximal impact in Asco, few kilometers downstream the plant, and a clear
      reduction at Xerta. This combination of chemical, molecular, cellular and
      physiological data allowed the precise assessment of the negative impact of the
      chlor-alkali plant on the quality of river sediments and on fish, and suggests
      that sediments may be a reservoir for toxic substances even in dynamic
      environments like rivers.

PMID- 20800877
TI  - Fate of the antiretroviral drug tenofovir in agricultural soil.
AB  - Tenofovir (9-(R)-(2-phosphonylmethoxypropyl)-adenine) is an antiretroviral drug
      widely used for the treatment of human immunodeficiency virus (HIV-1) and
      Hepatitis B virus (HBV) infections. Tenofovir is extensively and rapidly excreted
      unchanged in the urine. In the expectation that tenofovir could potentially reach
      agricultural lands through the application of municipal biosolids or wastewater,
      and in the absence of any environmental fate data, we evaluated its persistence
      in selected agricultural soils. Less than 10% of [adenine-8-(14)C]-tenofovir
      added to soils varying widely in texture (sand, loam, clay loam) was mineralized
      in a 2-month incubation under laboratory conditions. Tenofovir was less readily
      extractable from clay soils than from a loam or a sandy loam soil. Radioactive
      residues of tenofovir were removed from the soil extractable fraction with
      DT(50)s ranging from 24+/-2 to 67+22days (first order kinetic model) or 44+9 to
      127+55days (zero order model). No extractable transformation products were
      detectable by HPLC. Tenofovir mineralization in the loam soil increased with
      temperature (range 4 degrees C to 30 degrees C), and did not occur in autoclaved
      soil, suggesting a microbial basis. Mineralization rates increased with soil
      moisture content, ranging from air-dried to saturated. In summary, tenofovir was
      relatively persistent in soils, there were no extractable transformation products
      detected, and the response of [adenine-8-(14)C]-tenofovir mineralization to soil
      temperature and heat sterilization indicated that the molecule was biodegraded by
      aerobic microorganisms. Sorption isotherms with dewatered biosolids suggested
      that tenofovir residues could potentially partition into the particulate fraction
      during sewage treatment.

PMID- 20800878
TI  - Potential enzyme toxicity of oxytetracycline to catalase.
AB  - Oxytetracycline (OTC) is a kind of widely used veterinary drugs. The residue of
      OTC in the environment is potentially harmful. In the present work, the non
      covalent toxic interaction of OTC with catalase was investigated by the
      fluorescence spectroscopy, UV-vis absorption and circular dichroism (CD)
      spectroscopy at physiological pH 7.4. OTC can interact with catalase to form a
      complex mainly by van der Waals' interactions and hydrogen bonds with one binding
      site. The association constants K were determined to be K(293K)=7.09*10(4)Lmol(
      1) and K(311K)=3.31*10(4)Lmol(-1). The thermodynamic parameters (DeltaH degrees ,
      DeltaG degrees  and DeltaS degrees ) of the interaction were calculated. Based on
      the Forster theory of non-radiative energy transfer, the distance between bound
      OTC and the tryptophan residues of catalase was determined to be 6.48nm. The
      binding of OTC can result in change of the micro-environment of the tryptophan
      residues and the secondary structure of catalase. The activity of catalase was
      also inhibited for the bound OTC. This work establishes a new strategy to probe
      the enzyme toxicity of veterinary drug residues and is helpful for clarifying the
      molecular toxic mechanism of OTC in vivo. The established strategy can be used to
      investigate the potential enzyme toxicity of other small organic pollutants and
      drugs.

PMID- 20800879
TI  - Health risk assessment on dietary exposure to polycyclic aromatic hydrocarbons
      (PAHs) in Taiyuan, China.
AB  - Twenty-five kinds of seven categories of foods were sampled in December 2008 and
      the concentrations of 16 polycyclic aromatic hydrocarbons (PAHs) were determined.
      The highest level of total PAHs was detected in pork (195.30ng/g) whereas the
      lowest concentration was found in milk (8.73ng/g). The median values of B[a]P
      equivalent (B[a]P(eq)) daily exposure doses for children, adolescents, adults and
      seniors of male were estimated to be 392.42, 511.01, 571.56 and 532.56ng/d,
      respectively, whereas those for the above population groups of female were found
      to be 355.16, 440.51, 487.64 and 444.85ng/d, respectively. The incremental
      lifetime cancer risk (ILCR) values at the 22.1th, 26.1th, 12.7th, 24.9th, 22.7th,
      27.0th, 12.9th, and 25.5th percentiles for male children, male adolescents, male
      adults, male seniors, female children, female adolescents, female adults and
      female seniors, respectively, were larger than 10(-6), indicating high potential
      carcinogenic risk, and were larger than 10(-4) at the 74.5th, 78.7th, 60.6th,
      77.4th, 75.3th, 79.5th, 60.8th and 77.9th percentiles for the above groups,
      respectively, which implied significant cancer risk. Sensitivity analysis found
      that the two variables of oral cancer slope factor of benzo(a) pyrene (SF) and
      the daily dietary PAH exposure level (ED) had the greater impact than that of
      body weight (BW) on the ILCR.

PMID- 20800880
TI  - Estimation of prostate size in community-dwelling men.
AB  - OBJECTIVES: To use two population-based samples of prostate cancer-free men to
      develop and validate a novel multivariable equation for estimating prostate
      volume (PV). Previous investigators have demonstrated the ability to use serum
      prostate-specific antigen (PSA) levels to estimate PV in men without prostate
      cancer; however, the ability of additional clinical variables to further enhance
      PV estimation in these men remains unclear. METHODS: We applied linear regression
      modeling to data from an 80% random sample (n = 366) of the baseline cohort from
      the Olmsted County Study of Urinary Symptoms and Health Status among Men (OCS) to
      develop an equation for estimating PV in men without prostate cancer. We then
      evaluated the predictive ability of this equation by comparing estimated and
      measured PV values in 3 additional validation sets of men. RESULTS: The final
      linear regression model included PSA, age, and weight as independent predictors
      of PV. For prediction in baseline OCS men, the multiple correlation coefficients
      increased from 0.62(PSAalone) to 0.71(fullmodel). In addition, the area under the
      curve estimates from the receiver operating characteristic curves increased from
      0.79(PSAalone) to 0.85(fullmodel) for predicting PV >30 mL. CONCLUSIONS: Our data
      suggest that PV can be estimated with easily obtained clinical variables.
      Moreover, we demonstrate that age and weight can be added to PSA level to achieve
      greater accuracy in predicting PV. This methodology may prove useful for
      estimating PV in men in settings where costs and practicality preclude the use of
      imaging techniques.

PMID- 20800881
TI  - TMPRSS2-ERG gene fusion and clinicopathologic characteristics of Korean prostate
      cancer patients.
AB  - OBJECTIVES: To survey the status of TMPRSS2-ERG fusion in Korean prostate cancer
      patients, we assessed the differences in clinicopathologic characteristics and
      biochemical recurrence according to TMPRSS2-ERG fusion status. METHODS: The
      incidence of the TMPRSS2-ERG fusion gene was evaluated via fluorescence in situ
      hybridization (FISH) using ERG break-apart probes in 254 prostate cancer tissues
      resected by radical prostatectomy, and analyses of clinicopathologic parameters
      and biochemical recurrence were conducted. RESULTS: The fusion rate of the
      TMPRSS2-ERG gene was 20.9% (53/254). TMPRSS2-ERG gene fusion was identified more
      frequently in patients with low Gleason grade (primary Gleason pattern <= 3 or
      sum of Gleason score <= 7, P = .015 and .027). Patients with large cribriform
      glands in Gleason pattern 4 harbored a rare TMPRSS2-ERG fusion gene compared with
      patients without large cribriform glands (P = .027). The incidence of biochemical
      recurrence did not differ according to TMPRSS2-ERG fusion gene status (P = .598).
      CONCLUSIONS: ERG gene aberration did not correlate with biochemical recurrence of
      prostate cancers in Korean patients. Lower Gleason grade demonstrated higher
      rates of TMPRSS2-ERG fusion compared with high-grade tumors, including those
      demonstrating a large cribriform glands pattern. Prostate cancer with large
      cribriform glands revealed rare TMPRSS2-ERG gene fusion.

PMID- 20800882
TI  - Surgically corrected urethral diverticula: long-term voiding dysfunction and
      reoperation rates.
AB  - OBJECTIVES: To present the largest reported cohort of women with urethral
      diverticula and to evaluate the surgical outcomes and long-term voiding symptoms
      after urethral diverticulectomy. Studies evaluating the outcomes after urethral
      diverticulectomy have been limited by small patient numbers and short-term follow
      up. METHODS: Women who had undergone diverticulectomy at our institution from
      1996 to 2008 were mailed surveys. Urinary bother was assessed using the
      Urogenital Distress Inventory 6-item questionnaire, and patients were asked to
      report subsequent urethral or vaginal surgery and the number of urinary tract
      infections within the previous year. To determine the rate of surgical
      recurrence, the charts of women not responding to the survey were reviewed.
      RESULTS: A total of 122 women were identified as having undergone urethral
      diverticulectomy during the study period. Of these, 13 (10.7%) had an eventual
      recurrence that required repeat surgical excision. Patients with a proximal
      diverticulum, multiple diverticula, or previous pelvic or vaginal surgery
      (excluding previous diverticulectomy) were more likely to develop recurrence (P =
      .01, P = .03, and P < .001, respectively). For the 61 women (50%) responding to
      our survey, the mean follow-up was 50.4 months. Of these 61 women, 24 (39.3%) had
      had a urinary tract infection within the previous year, with 14 (23%) women
      having had >=3 within the previous year. Also, 16 (26.2%) had persistent pain or
      discomfort with urination. The mean +/- SD total Urogenital Distress Inventory-6
      score was 31.1 +/- 25.5 for the survey responders. CONCLUSIONS: To our knowledge,
      our study represents the largest study with the longest follow-up after urethral
      diverticulectomy. Patients with proximal or multiple diverticula and those with
      previous pelvic surgery should be counseled appropriately regarding the risks of
      recurrence and persistent voiding dysfunction.

PMID- 20800883
TI  - Cholesterol embolization to bladder in setting of transient ischemic attack and
      hematochezia: an unusual presentation of cholesterol embolization syndrome.

PMID- 20800884
TI  - Urinary prostaglandin E2 was increased in patients with suprapontine brain
      diseases, and associated with overactive bladder syndrome.
AB  - OBJECTIVE: To investigate the association between the urinary levels of
      prostaglandins (PGE(2) and PGF(2alpha)), nerve growth factor (NGF) and substance
      P, and overactive bladder (OAB) symptoms in patients with suprapontine brain
      diseases. MATERIALS AND METHODS: The subjects were 114 patients in the chronic
      phase of a brain disease and 27 healthy controls with no brain disease or lower
      urinary tract symptoms (LUTS). The OAB symptoms were assessed with the OAB
      symptom score and the subjects were then classified into 5 groups: healthy
      control, patients without LUTS, increased bladder sensation (IBS), OAB dry, and
      OAB wet. Urinary mediator concentrations were measured using enzyme-linked
      immunosorbent assay and normalized to the urinary creatinine concentration, and
      then compared among the 5 groups. RESULTS: The urinary PGE(2) level was
      significantly higher in patients with brain diseases than in healthy controls,
      even in the patients without any OAB symptoms, and compared with patients without
      LUTS, a significant increase in the urinary PGE(2) was observed in patients with
      OAB dry or wet (P = .004 or .015, respectively). The PGF(2alpha) level showed a
      significant increase in OAB wet compared with patients without LUTS (P = .001).
      The urinary levels of NGF and substance P were not significantly associated with
      OAB as a result of this type of brain disease. CONCLUSION: The urinary PGE(2)
      level was putatively elevated in patients with suprapontine brain diseases and
      associated with the presence of OAB. The PGF(2alpha) level may also be associated
      with OAB.

PMID- 20800885
TI  - Multiple circumferential urethrocutaneous fistulae as a rare complication of
      circumcision and review of literature.
AB  - Circumcision remains the most common surgical procedure performed in boys
      worldwide. Although circumcision can be associated with numerous major and minor
      complications, urethrocutaneous fistula is extremely rare and serious. An 18
      years-old boy presented with urine passage from 4 fistula orifices. He had been
      circumcised by nonmedical personnel when he was 2 years old. During the surgery,
      after degloving the penis, it was observed that the fistulae tracts were
      combining. There were only 2 fistulae orifices on the urethra. The fistulae were
      repaired with simple closure. This is the second case reported in the literature
      describing multiple urethrocutaneous fistulae.

PMID- 20800886
TI  - Intravesical electromotive botulinum toxin type A administration--part II:
      Clinical application.
AB  - OBJECTIVES: To assess the effect of electromotive botulinum toxin type A
      administration on urodynamic variables, urinary/fecal incontinence, and
      vesicoureteral reflux (VUR) due to refractory neurogenic detrusor overactivity in
      children with myelomeningocele. METHODS: A total of 15 children (mean age 7.8
      years) were included. Using a specially designed catheter, 10 IU/kg of
      electromotive botulinum toxin type A was inserted into the distended bladder.
      While connected to the indwelling catheter and 2 dispersive pads, a pulsed
      current generator delivered 10 mA for 15 minutes. The urodynamic parameters,
      including reflex volume, maximal bladder capacity, maximal detrusor pressure, and
      end-fill pressure, and the urinary/fecal incontinence status and VUR grade were
      evaluated before and at 1, 4, and 9 months after treatment. RESULTS: The mean
      reflex volume and maximal bladder capacity had increased considerably (99 +/- 35
      mL versus 216 +/- 35 mL and 121 +/- 39 mL versus 262 +/- 41 mL, respectively; P <
      .001). In contrast, the mean maximal detrusor pressure and end-fill pressure had
      significantly decreased (75 +/- 16 cm H(2)O versus 39 +/- 10 cm H(2)O and 22 +/-
      7 cm H(2)O versus 13 +/- 2 cm H(2)O) after treatment. The difference was
      statistically significant (P < .001). Urinary incontinence improved in 12
      patients (80%). The VUR grade substantially decreased in 7 of the 12 children
      (mean VUR grade 2.25 +/- 1.3 versus 1.37 +/- 0.7; P = .001), and none of the
      children required surgical intervention. Fecal incontinence was alleviated in 10
      (83.3%) of the 12 children. Skin erythema and burning sensation were observed in
      6 children. CONCLUSIONS: The results of our study have shown that electromotive
      botulinum toxin type A administration is a feasible and safe method with no need
      for anesthesia. This novel delivery system resulted in considerable improvement
      in the urodynamic parameters, urinary/fecal incontinence, and VUR in patients
      with refractory neurogenic detrusor overactivity.

PMID- 20800887
TI  - Concordance between one-hour pad test and subjective assessment of stress
      incontinence.
AB  - OBJECTIVES: To examine the concordance among the 1-hour pad test results,
      subjective questions regarding incontinence, and a quality-of-life questionnaire
      to assess the role of the pad test as a noninvasive measurement tool in clinical
      trials. The 1-hour nonstandard pad test is one of several quantitative tools used
      to measure urinary incontinence; however, its utility has been questioned.
      METHODS: The study subjects were women participating in 2 clinical trials
      evaluating noninvasive interventions: circular muscle exercises versus pelvic
      floor muscle training for urinary incontinence. The quantity of urinary leakage
      according to the pad test and questions regarding subjective urinary leakage from
      the quality-of-life questionnaire were evaluated for all study subjects combined
      and in subgroups. RESULTS: A total of 731 clinical pad tests were evaluated from
      the 2 trials. Significant associations were found between several questions
      regarding subjective leakage and the pad test results in the study subgroups. A
      significant correlation was seen between the pad test results and the quality-of
      life questionnaire scores (r = 0.14 before intervention and r = 0.42 after
      intervention in the combined studies; P < .05). CONCLUSIONS: The 1-hour pad test
      demonstrated concordance with subjective assessment tools for urinary
      incontinence and should be considered a part of the armamentarium for assessing
      the severity of this condition.

PMID- 20800888
TI  - Urachal catheter provides new choice for long-term urinary diversion in prune
      belly syndrome.
AB  - Prune belly syndrome has been identified as a clinical triad of abdominal muscle
      deficiency, bilateral cryptorchidism, and urologic abnormalities. We present the
      case of a discordant monozygotic twin with prune belly syndrome and voiding
      dysfunction that was relieved by long-term urinary catheterization by way of the
      urachus. To the best of our knowledge, this alternative method has not been
      previously reported. We suggest that for newborn infants with long-term voiding
      dysfunction, if the urachus retains patency, urinary catheterization through the
      urachus could be a choice for urine drainage instead of cystostomy, providing a
      better cosmetic appearance and quality of life.

PMID- 20800889
TI  - Long-term outcomes of dismembered pyeloplasty for midline-crossing giant
      hydronephrosis caused by ureteropelvic junction obstruction in children.
AB  - OBJECTIVES: To assess the long-term surgical outcomes of dismembered pyeloplasty
      for congenital midline-crossing giant hydronephrosis (GH) caused by ureteropelvic
      junction obstruction (UPJO). METHODS: From June 1986 to September 2005, 167
      unilateral UPJO pediatric patients who underwent dismembered pyeloplasty
      performed by a single surgeon were retrospectively analyzed. The patients were
      followed up for more than 5 years. Differential renal function (DRF) assessed by
      DTPA renal scan more than 3 years postoperatively was compared between GH and non
      GH children. Improvement in renal parenchymal thickness (RPT) on ultrasonography
      at 5 years postsurgery was also compared. In GH children, surgical outcomes were
      compared based on the age at operation and whether preoperative nephrostomy was
      performed. RESULTS: DRF measured more than 3 years postoperatively was 33 +/- 14%
      versus 48 +/- 12% (P < .05), and the improvement of RPT was 4 +/- 2 mm (181%)
      versus 5 +/- 4 mm (168%) in GH (n = 25) and non-GH (n = 142) children,
      respectively (P = .305). GH patients who underwent pyeloplasty before 12 months
      of age (n = 13) experienced more improvement in RPT (192% vs 102%) compared with
      GH patients who underwent surgery after 12 months of age (n = 12) (P < .05). The
      surgical outcomes for RPT improvement or long-term DRF were not different based
      on whether preoperative nephrostomy was performed. No children developed
      hypertension or elevated serum creatinine. CONCLUSIONS: Long-term surgical
      outcomes after dismembered pyeloplasty for GH were satisfactory. In children with
      GH caused by UPJO, early relief of obstruction allows comparable nephron sparing.

PMID- 20800890
TI  - Experience of retroperitoneal laparoscopic treatment on pheochromocytoma.
AB  - OBJECTIVES: To evaluate the safety and efficacy of retroperitoneal laparoscopic
      resection for pheochromocytoma. METHODS: The clinical data of 131 cases of
      pheochromocytoma were analyzed retrospectively. There were 69 males and 62
      females with an age range of 8 to 77 years, including 120 cases of adrenal
      pheochromocytoma and 11 extraadrenal pheochromocytomas. Retroperitoneal
      laparoscopic resection was performed in all cases. We divided our practical
      experience into three stages: (1) the tentative and exploratory stage, (2) the
      accumulative stage, and (3) the mature stage. RESULTS: During the tentative and
      exploratory stage, 10 patients underwent retroperitoneal laparoscopic surgery.
      The mean diameter of the tumor was 4.2 cm. The mean operation time was 105
      minutes, and the median volume of blood loss during surgery was 450 mL. During
      the accumulative stage, the mean tumor diameter of the 72 cases was 5.6 cm. The
      mean operation time was 85 minutes and median volume of blood loss was 140 mL.
      During the mature stage, the mean tumor diameter of the 49 cases (including 11
      extra-adrenal pheochromocytoma patients) was 6.7 cm. The mean operation time was
      75 minutes and median volume of blood loss was 70 mL. Follow-ups ranging from 1
      to 70 months were conducted, with three cases recurring. There were no cases of
      distant metastases or death. CONCLUSIONS: Retroperitoneal laparoscopic surgery
      for pheochromocytoma is feasible and safe. This procedure will be increasingly
      performed as medical personnel continue to develop their skills and accumulate
      experience.

PMID- 20800891
TI  - Predicting romantic involvement, relationship cognitions, and relationship
      qualities from physical appearance, perceived norms, and relational styles
      regarding friends and parents.
AB  - Using a sample of 199 adolescents, the present study examined Furman and Wehner's
      (1999) hypothesis that the predictors of the degree of romantic involvement and
      the predictors of romantic relationship cognitions and qualities differ. As
      hypothesized, physical appearance and friends' normative romantic involvement
      were related to the degree of casual and serious romantic involvement, whereas
      relational styles regarding friends and parents were unrelated in almost all
      cases. On the other hand, relational styles regarding friends and parents were
      related to supportive and negative romantic interactions and romantic styles. In
      contrast, physical appearance and friends' normative romantic involvement were
      generally unrelated to interactions and romantic styles. Physical appearance was
      also related to romantic appeal and satisfaction.

PMID- 20800892
TI  - Effects of small pulsed nanocurrents on cell viability in vitro and in vivo:
      implications for biomedical electrodes.
AB  - Using a custom-built, implantable pulse generator, we studied the effects of
      small pulsed currents on the viability on rat aortic-derived cells (RAOC) in
      vitro. The pulsed currents (0.37A/m(2)) underwent apoptosis within 24h as shown
      by the positive staining for cleaved caspase-3 and classically apoptotic
      morphology. Based on these findings, we examined the effects of nanocurrents in
      vivo. The pulse generator was implanted subcutaneously in the rat model. The
      electrode|tissue interface histology revealed no difference between the active
      platinum surface and the neighboring control surface, however we found a large
      difference between electrodes that were functional during the entire experiment
      and non-active electrodes. These non-active electrodes showed an increase in
      impedance at higher frequencies 21 days post-implantation, whereas working
      electrodes retained their impedance value for the entire experiment. These
      results indicate that applied currents can reduce the impedance of implanted
      electrodes.

PMID- 20800894
TI  - Activating protein-1 family of transcription factors in the human placenta
      complicated by preeclampsia with and without fetal growth restriction.
AB  - Preeclampsia (PE) is a serious disorder of human pregnancy, it is often
      associated with fetal growth restriction (FGR) which is a failure of the fetus to
      reach its own growth potential. Activator protein-1 (AP-1) is a family of
      transcription factors inducible in response to a variety of extracellular stimuli
      and functions. AP-1 plays a complex role in the regulation of different
      fundamental cellular processes, including cell proliferation, survival, death and
      transformation. We investigate the expression pattern of AP-1 transcription
      factors in normal placentas during gestation and in placentas from PE without and
      with FGR using semiquantitative RT-PCR and immunohistochemistry techniques. The
      most interesting data concern the alterations of protein expression patterns of c
      fos, Jun D and c-jun in normal gestation as well as in PE and PE-FGR pathologies.
      In addition, alterations but not significant changes are detected in mRNA
      expressions for these transcription factors. We strongly suggest that c-fos is
      implicated in regulating invasiveness mechanism of extravillous trophoblast in
      normal gestation as well as in PE placentas. In addition, we suggest that the
      opposite modulation of Jun D and c-jun in PE and PE-FGR supports the recent
      hypothesis that PE and PE-FGR could be considered two pathologies with different
      origin (maternal and placental) each of which has a different molecular pattern
      of expression.

PMID- 20800893
TI  - Citric acid-derived in situ crosslinkable biodegradable polymers for cell
      delivery.
AB  - Herein, we report a first citric acid (CA)-derived in situ crosslinkable
      biodegradable polymer, poly(ethylene glycol) maleate citrate (PEGMC). The
      synthesis of PEGMC could be carried out via a one-pot polycondensation reaction
      without using organic solvents or catalysts. PEGMC could be in situ crosslinked
      into elastomeric PPEGMC hydrogels. The performance of hydrogels in terms of
      swelling, degradation, and mechanical properties were highly dependent on the
      molar ratio of monomers, crosslinker concentration, and crosslinking mechanism
      used in the synthesis process. Cyclic conditioning tests showed that PPEGMC
      hydrogels could be compressed up to 75% strain without permanent deformation and
      with negligible hysteresis. Water-soluble PEGMC demonstrated excellent
      cytocompatibilty in vitro. The degradation products of PPEGMC also showed minimal
      cytotoxicity in vitro. Animal studies in rats clearly demonstrated the excellent
      injectability of PEGMC and degradability of the in situ-formed PPEGMC. PPEGMC
      elicited minimal inflammation in the early stages post-injection and was
      completely degraded within 30 days in rats. In conclusion, the development of CA
      derived injectable biodegradable PEGMC presents numerous opportunities for
      material innovation and offers excellent candidate materials for in situ tissue
      engineering and drug delivery applications.

PMID- 20800896
TI  - Setting priorities for comparative effectiveness research: a case study using
      primary open-angle glaucoma.
AB  - OBJECTIVE: To test the feasibility of a framework for prioritizing new
      comparative effectiveness research (CER) questions related to management of
      primary open-angle glaucoma (POAG) using practice guidelines and a survey of
      clinicians. DESIGN: Cross-sectional survey. PARTICIPANTS: Members of the American
      Glaucoma Society (AGS). METHODS: We restated as an answerable clinical question
      each recommendation in the 2005 American Academy of Ophthalmology Preferred
      Practice Patterns (PPPs) regarding the management of POAG. We asked members of
      the AGS to rank the importance of each clinical question, on a scale of 0 (not
      important at all) to 10 (very important), using a 2-round Delphi survey conducted
      online between April and September 2008. Respondents had the option of selecting
      "no judgment" or "research has already answered this question" to each question
      in lieu of the 0 to 10 rating. We used the ratings assigned by the Delphi
      respondents to determine the importance of each clinical question. MAIN OUTCOME
      MEASURES: Ranking of importance of each clinical question. RESULTS: We derived 45
      clinical questions from the POAG PPPs. Of the 620 AGS members invited to
      participate in the survey, 169 completed the Round 1 survey; 105 of 169 also
      completed Round 2. We observed 4 response patterns to the individual questions.
      Nine clinical questions were ranked as the most important: 4 questions on medical
      intervention, 4 questions on filtering surgery, and 1 question on adjustment of
      therapy. CONCLUSIONS: Our theoretical model for priority setting for CER
      questions is a feasible and pragmatic approach that merits testing in other
      medical settings.

PMID- 20800895
TI  - Complement regulates TLR4-mediated inflammatory responses during intestinal
      ischemia reperfusion.
AB  - Innate immune responses including TLR4 and complement activation are required for
      mesenteric ischemia/reperfusion (IR)-induced tissue damage. We examined the
      regulation of TLR4 and complement activation in a mouse model of intestinal IR.
      Intestinal IR-induced C3 deposition in a TLR4 dependent manner. In addition, in
      wild-type but not TLR4 deficient mice, IR significantly increased C3 and Factor B
      (FB) mRNA expression within the intestine. To further examine the role of TLR4
      and complement, we administered the complement inhibitor, CR2-Crry, to target
      local complement activation in wild-type C57Bl/10, and TLR4 deficient B10/ScN
      mice. TLR4 deficient mice sustained less damage and inflammation after IR than
      wild-type mice, but administration of CR2-Crry did not further reduce tissue
      damage. In contrast, CR2-Crry treatment of wild-type mice was accompanied by a
      reduction in complement activation and in C3 and FB transcription in response to
      IR. CR2-Crry also significantly decreased intestinal IL-6 and IL-12p40 production
      in both the wild-type and TLR4 deficient mice. These data indicate that TLR4
      regulates extrahepatic complement production while complement regulates TLR4
      mediated cytokine production during intestinal IR.

PMID- 20800897
TI  - N-acetyl cysteine add-on treatment for bipolar II disorder: a subgroup analysis
      of a randomized placebo-controlled trial.
AB  - BACKGROUND: The evidence base for the pharmacological treatment of bipolar II
      disorder is limited. In bipolar disorder, there is evidence for glutathione
      depletion and increased oxidative stress, as well as dysregulation of glutamate;
      N-acetyl cysteine (NAC) has effects on both of these systems. Add-on NAC has been
      shown to have a significant benefit on depressive symptoms in a randomized
      placebo-controlled trial. In this report, we explore the effects of this compound
      in a subset of patients with bipolar II disorder from that trial. METHODS:
      Individuals were randomized to NAC or placebo in addition to treatment as usual,
      in a double-blind fashion. Mood and functional outcomes were assessed up to 24
      weeks of treatment. RESULTS: Fourteen individuals were available for this report,
      seven in each group. Six people achieved full remission of both depressive and
      manic symptoms in the NAC group; this was true for only two people in the placebo
      group (chi(2)=4.67, p=0.031). LIMITATIONS: Subgroup analyses in a small subsample
      of patients. Not all participants had elevated depression scores at baseline.
      CONCLUSION: Notwithstanding all the limitations that subgroup analysis of trials
      carry, this data could serve as a hypothesis-generating stimulus for further
      clinical trials of pharmacologic treatment for bipolar II depression.

PMID- 20800898
TI  - Long-term outcomes of participants in a perinatal depression early detection
      program.
AB  - BACKGROUND: Long-term follow-up studies are required to better understand the
      extent of the effectiveness of early detection programs for perinatal depression.
      We followed up participants in such a program to investigate the long-term
      depression, treatment and relationship outcomes of mothers originally identified
      as 'probably depressed' (screened positive). METHODS: At 2 years postpartum all
      participants who had 'screened positive' (N=159) and a random sample of
      participants who had 'screened negative' were invited to participate in a mailed
      survey. Measures included: current mood; coping; access to treatment; quality of
      partner relationship; and mother-infant bonding. RESULTS: Mothers originally
      detected as probably depressed (n=98) fared significantly worse than 'screened
      negative' mothers (n=101) both in terms of their higher mean depression scores
      (EPDS: Ms=11.0 vs. 6.4) and greater proportions categorised as probably depressed
      at 2 years postpartum (40% vs. 11% respectively, p<.001, phi=.33). Elevated
      depression symptoms at 2 years postpartum were associated with poorer partner
      relationships and mother-infant bonding. Moreover, there appears to be a double
      dose effect for women who screen positive on two occasions. Thirty-seven percent
      of depressed mothers did not take up treatment, frequently citing a preference
      for using their own resources. LIMITATIONS: Limitations include the use of self
      report measures to assess depression symptoms and mother-infant bonding.
      Treatment data was collected retrospectively. CONCLUSIONS: Despite being offered
      treatment options, a substantial proportion of women who screened positive had
      poor long-term mental health and relationship outcomes. This paper discusses some
      of the implications for perinatal early detection and treatment programs.

PMID- 20800899
TI  - Uterine natural killer cells in peri-implantation endometrium from women with
      repeated implantation failure after IVF.
AB  - Several studies have suggested that endometrial uNK (CD56+) cells may play a role
      in implantation. The aim of this study was to investigate the number of CD56+,
      CD16+ and CD69+ cells in the unstimulated endometrium of women with recurrent
      implantation failure after IVF. The percentage of stromal cells positive for
      CD56, CD16 and CD69 was identified by immunocytochemistry in endometrial biopsies
      from 15 normal control women and 40 women with recurrent implantation failure.
      All biopsies were obtained on days LH+7 to LH+9. The density of CD56+ cells in
      endometrium from women with repeated implantation failure after IVF [median
      (range) CD56+ cell density=14.5% (1.5-71.4%)] was significantly higher (P=0.005)
      than in endometrium from control women [5% (2.1-19.2%)]. There was no significant
      difference in the densities of CD16+ and CD69+ cells in the endometrium from
      women in the two groups. The increased density of CD56+ cells in the endometrium
      of women with recurrent implantation failure suggests that these cells are
      directly involved in the implantation process; alternatively this may indicate a
      general endometrial defect in these women, which leads to the inability of the
      embryo to implant.

PMID- 20800900
TI  - A cross-cultural comparison between Spain and the USA: temperament and character
      distribution by sex and age.
AB  - The Unified Biosocial Theory of Personality developed by Cloninger has been
      applied in different cultures. Distribution by age and sex of the Temperament and
      Character Inventory (TCI) dimensions were assessed cross-culturally for samples
      in Spain and the USA. Three non-clinical samples were included: i) 404
      participants from Asturias (Spain); ii) 240 participants from Burgos (Spain); and
      iii) 300 adults from St. Louis (USA). Each participant was assessed by means of
      the TCI. A significant negative correlation between NS and both HA (r=-0.329;
      P<0.01) and P (r=-0.217; P<0.01) was found in the study sample, as well as
      significant effects of age in NS, HA, RD, and C for women and in NS and HA for
      men, and also of sex in HA and RD. Personality dimensions for the two Spanish
      samples appear to be similar (differences in HA4 and RD) compared to those for
      the US sample (differences in NS, HA, RD and P). Findings support Cloninger's
      theory about differences between men and women, but not regarding the
      intercorrelations between temperament dimensions.

PMID- 20800901
TI  - Serotonin transporter polymorphism as a predictor for escitalopram treatment of
      major depressive disorder comorbid with alcohol dependence.
AB  - The aim of this study was to determine whether the serotonin transporter gene
      polymorphism (5-HTTLPR) is associated with the treatment outcomes of escitalopram
      for patients with comorbid major depression and alcohol dependence. Eighty
      treatment-seeking patients were randomly assigned to either receive 20mg of
      escitalopram or a control of 20mg of the non-serotonergically acting memantine.
      Depression was measured by the Montgomery-Asberg Depression Rating Scale (MADRS)
      and alcoholism by the Alcohol Use Disorders Identification Test (AUDIT). Twenty
      nine participants in each treatment group completed the study, and from those DNA
      was given by 27 in the escitalopram group and 21 in the memantine group. In the
      escitalopram group linear regression showed that LL genotype predicted greater
      decrease in MADRS scores compared with the SS/SL genotypes (p=0.04) after a
      3month treatment period. Moreover, each L allele associated with MADRS score
      decrease by 15% (p=0.04) in the escitalopram group. In the memantine group,
      however, no association between LL genotype and MADRS decrease was detected.
      AUDIT decrease was not associated with the 5-HTTLPR genotype for either
      medication. This is the first study in the treatment of depression in dual
      diagnosis patients to report a significant association between outcomes with
      escitalopram and the 5-HTTLPR gene polymorphism.

PMID- 20800902
TI  - Factor structure of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) in a large
      sample of patients with schizophrenia or related disorders and comorbid obsessive
      compulsive symptoms.
AB  - In the past decade there has been an increasing interest in the levels of
      obsessive-compulsive symptoms (OCS) found in patients with schizophrenia or
      related disorders. The widely acknowledged gold standard measure of the severity
      of OCS is the content-free version of the Yale-Brown Obsessive-Compulsive Scale
      (Y-BOCS) (Goodman et al., 1989a,b). However, factor analytic research in patients
      with obsessive-compulsive disorder (OCD) provided varied results. So far no study
      has been conducted on the factor structure of the Y-BOCS in patients with
      schizophrenia. The present study addresses this issue. We administered the Y-BOCS
      in a sample of 217 patients with schizophrenia or related disorders and comorbid
      OCS who participated in a multicentre cohort study. We used principal component
      analysis (PCA) to explore the underlying factor structure. A two-factor solution
      consistent with the originally proposed scoring structure of the Y-BOCS provided
      the optimal fit. We also found some support for a three-factor solution
      consistent with earlier findings by Kim et al. and Moritz et al. (Kim et al.,
      1994; Moritz et al., 2002). The produced factors showed good reliability and
      strong correlations with the Y-BOCS Total score. However, the resistance to
      compulsion item failed to demonstrate adequate correlation to the Total score, a
      finding consistent with earlier findings in several studies with patients with
      OCD.

PMID- 20800903
TI  - Self-mutilative behaviours in male alcohol-dependent inpatients and relationship
      with posttraumatic stress disorder.
AB  - The aim of this study was to investigate the relationship between self-mutilation
      (SM) and posttraumatic stress disorder (PTSD) in male alcohol-dependent
      inpatients, and to examine whether there is something unique about self
      mutilaters with the PTSD/alcohol-dependence co-morbidity, compared with self
      mutilaters without PTSD in this population. Participants were 156 consecutively
      admitted male alcohol-dependent inpatients. Patients were investigated with the
      Self-mutilative Behaviour Questionnaire (SMBQ), the Traumatic Experiences
      Checklist (TEC), the Clinician Administered PTSD Scale (CAPS), the Symptom
      Checklist-Revised (SCL-90-R) and the Michigan Alcoholism Screening Test (MAST).
      Among alcohol-dependent inpatients, 34.0% (n=53) were considered as group with
      SM. Rate of being unemployed, history of any trauma, history of suicide attempt
      and lifetime PTSD diagnosis were higher, whereas being married, current age, age
      at onset of regular alcohol use and duration of education were lower in the group
      with SM. Mean scores of SCL-90 subscales, TEC and MAST were higher in the SM
      group. Although SM might be related with PTSD among male alcohol-dependent
      inpatients, predictors of SM were age at onset of regular alcohol use, history of
      suicide attempt, anxiety, depression and hostility. Age at onset of regular
      alcohol use, history of suicide attempt, anxiety, depression and somatisation
      predicted SM in the subgroup of patients without PTSD, whereas hostility
      predicted SM alone in the subgroup of patients with PTSD. Results support the
      anti-suicide and the affect-regulation models of SM in the non-PTSD group,
      whereas they support the hostility model of SM in the subgroup with PTSD in
      alcohol-dependent inpatients. Thus, to reduce self-mutilative behaviour
      (SMB)among alcohol-dependent patients, clinicians must address different subjects
      in different subgroup patients; that is, focussing hostility in those with PTSD
      co-morbidity.

PMID- 20800904
TI  - Membrane fatty acid levels as a predictor of treatment response in chronic
      schizophrenia.
AB  - Abnormal fatty acid composition in neural membranes, that is, the balance between
      essential polyunsaturated fatty acids (EPUFAs) and saturated fatty acids, has
      been suggested to be related to the psychotic symptoms and cognitive impairment
      of schizophrenia. This study was conducted to test the hypothesis that the
      ability of atypical antipsychotic drugs to ameliorate positive symptoms and
      cognitive function relevant to daily living would be predicted by baseline EPUFAs
      concentrations in the erythrocyte membrane in subjects with schizophrenia. A
      total of 24 actively psychotic patients with schizophrenia participated in the
      study. After blood drawing, they were treated with olanzapine or perospirone. The
      Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for Assessment
      of Negative symptoms (SANS), as well as the script tasks, a measure of event
      schema recognition, were administered at baseline and 3months after the start of
      treatment. Erythrocyte membrane fatty acid levels were analysed using a gas
      chromatography system. Scores of SAPS and SANS, as well as script task
      performance, were improved during treatment with either antipsychotic drug.
      Regression analysis indicates baseline EPUFAs concentrations were positively and
      negatively related with percent improvement of positive symptoms and script task
      performance, respectively. The results of this study suggest composition of
      phospholipids in the erythrocyte membrane provide a feasible marker to predict
      treatment response in patients with schizophrenia.

PMID- 20800905
TI  - Expression of oxidative stress-response genes is not activated in the prefrontal
      cortex of patients with depressive disorder.
AB  - To test the hypothesis that the oxidative stress consistently detected in the
      peripheral blood of patients with depressive disorder impacts on the functionally
      relevant brain region, the expression level of nine major genes of the stress
      response and repair systems has been quantified in the prefrontal cortex of 24
      depressive and 12 control subjects. These genes were: superoxide dismutase
      (SOD1), SOD2, catalase (CAT), gluthatione peroxidase 1 (GPx1), 8-oxoguanine DNA
      glycosylase (OGG1), nei-like 1 (NEIL1), methionine sulphoxide reductase A (MSRA),
      telomere repeat-binding factor 2 (TERF2) and C-FOS. Telomere length (a maker of
      chronic exposure to oxidative stress) has been measured in the DNA of the
      occipital cortex. No significant difference has been found between the compared
      groups. It must be concluded that the pathogenic role of the oxidative stress in
      the cerebral mechanism of depression cannot be inferred from the alteration of
      peripheral parameters.

PMID- 20800906
TI  - Low dose combination steroids control autoimmune mouse hearing loss.
AB  - The severe side effects of glucocorticoids prevent long term management of
      hearing loss. Alternative steroid treatments that minimize or eliminate these
      effects would significantly benefit therapeutic control of hearing disorders. A
      steroid treatment study of autoimmune mouse hearing loss was conducted to
      determine the efficacy of combining aldosterone and prednisolone at low doses. An
      assessment also was made of low dose fludrocortisone, a synthetic
      mineralocorticoid that also has a slight glucocorticoid effect. MRL/MpJ-Fas(lpr)
      mice were tested for baseline ABR thresholds at 3 months of age and then treated
      with aldosterone (3.0 MUg/kg) or prednisolone (1.0 mg/kg) to determine the lowest
      effective dose of each. Other mice were given the two steroids in combination at
      doses of Pred 0.5 mg+Aldo 1.5 MUg; Pred 1.0 mg+Aldo 3.0 MUg; or Pred 1.5 mg+Aldo
      5.0 MUg. Mice were retested with ABR at 1 and 2 months to determine the efficacy
      of the different steroid treatments in controlling hearing loss. Another series
      of mice were given the synthetic mineralocorticoid fludrocortisone at low (2.8
      MUg/kg) or high (10 MUg/kg) doses and retested at monthly intervals for 3 months.
      Autoimmune mouse hearing loss developed in untreated controls. This threshold
      elevation was not prevented by prednisolone at 1 mg/kg or by aldosterone at 3
      MUg/kg when each was given alone. However, the two steroids combined at these
      doses effectively controlled hearing loss. The fludrocortisone treatments also
      were effective at low doses in preventing or reversing the autoimmune mouse
      hearing loss. This efficacy of combined steroids at low doses suggests the
      potential for reducing the side effects of glucocorticoids in the therapeutic
      control of hearing disorders.

PMID- 20800907
TI  - Common variation in the MOG gene influences transcript splicing in humans.
AB  - Multiple sclerosis (MS) is a complex autoimmune disease characterised by
      demyelinating lesions in the central nervous system (CNS) and myelin
      oligodendrocyte glycoprotein (MOG), a CNS-restricted protein expressed on the
      outer cell membrane of oligodendrocytes, has been linked with disease
      pathogenesis. We have investigated whether expression of MOG in post-mortem human
      brain tissue is associated with genetic variations in the MOG gene that have
      previously been associated with genetic susceptibility to MS (520G>A, rs3130253,
      V145I and 511G>C, rs2857766, V142L). Using quantitative reverse transcriptase PCR
      (qPCR), we found that the haplotype containing the 520A (rs3130253A, I145) allele
      is associated with a 1.7-fold increase in splicing of exon 2 to exon 3, which
      encodes the extracellular and transmembrane domains of MOG. Using predictive
      algorithms, we found that the 520G>A variant also alters a putative exonic
      splicing enhancer (ESE) involving the SC35 and SRp55 RNA-binding proteins,
      supporting the notion that this variation has a regulatory effect. No consistent
      differences in allele-specific expression were observed for any of the SNPs using
      the SNaPshot(r) method. In this exploratory study we have observed that changes
      in splicing, but not expression levels, are associated with common genetic
      variation in the MOG gene. Further work is now required to confirm these data and
      determine whether this altered MOG expression profile, which is predicted to be
      over-represented in Northern Europeans with MS, is relevant to the
      pathophysiology of this debilitating disease.

PMID- 20800908
TI  - Increased intramuscular nerve branching and inhibition of programmed cell death
      of chick embryo motoneurons by immunoglobulins from patients with motoneuron
      disease.
AB  - Massive programmed cell death (PCD) of developing chick embryo motoneurons (MNs)
      occurs in a well defined temporal and spatial sequence between embryonic day (E)
      6 and E10. We have found that, when administered in ovo, either circulating
      immunoglobulins G (IgGs) or cerebrospinal fluid from patients with MN disease can
      rescue a significant number of chick embryo MNs from normally occurring PCD. An
      increase of branching of intramuscular nerves was also observed that may account
      for the rescuing effects of pathologic IgGs. Proteomic analysis and further
      analysis by ELISA indicated that these effects may be mediated by the interaction
      of circulating human immunoglobulins with proteins of the semaphorin family.

PMID- 20800909
TI  - Inter-observer reliability of localization of recorded stridor sounds in
      children.
AB  - OBJECTIVE: To determine the inter-observer reliability in localization of
      recorded stridor sounds in children. METHOD: The stridor sounds of 28 children
      programmed for laryngobronchoscopy were recorded with a high quality digital
      recorder. Nineteen of these recordings with a diagnosis confirmed by endoscopy,
      were presented to otorhinolaryngology residents, academic specialists and non
      academic consultants (n=38) in different situations with and without additional
      information about the subject. The participants were requested to score the
      sounds as pharyngeal, supraglottic, glottic, subglottic or tracheal in both
      situations. The scores were analyzed per group of participants, per location of
      obstruction and per diagnosis in the different situations. RESULTS: The
      performance of the total group was just above chance level with an average score
      of 29.6%. The total results improved slightly with the additional information
      present, although not significantly. No significant difference was found between
      the three categories of participants. The supraglottic sounds were significantly
      better differentiated from the other locations in both assessment types
      (p<0.001). The tracheal region (p<0.01) and the supraglottic region (p<0.05)
      received significantly higher scores when the additional information was present.
      Laryngomalacia was significantly better differentiated (p<0.001) from the other
      diagnoses. The improvement in assessment with and without additional information
      present was significant for laryngomalacia (p=0.002) and tracheomalacia
      (p<0.035). CONCLUSION: The clinical observation of stridor in children shows poor
      levels of localization. Even though the two most common diagnoses, laryngomalacia
      and tracheomalacia are localized more correctly, the general performance is not
      significantly higher than random. No evidence was found in this study for
      differences in results by the observer's level of experience. We would recommend
      that an observational policy is only adequate when clear clinical signs are
      present that indicate laryngomalacia as first differential diagnosis. In other
      cases rigid and flexible endoscopy is indicated to locate the site and nature of
      obstruction.

PMID- 20800910
TI  - White matter hyperintensities (WMH) are associated with intracranial
      atherosclerosis rather than extracranial atherosclerosis.
AB  - There is increasing evidence for an association between WMH and large-artery
      atherosclerosis. We evaluated 268 patients with acute ischemic stroke to assess
      the relationship between intracranial (IC) atherosclerosis and WMH. The patients
      were classified into three groups according to the location of the stenosis; IC,
      extracranial (EC), and non-stenosis (NS) group. WMH were rated using the
      semiquantitative method of Scheltens and coworkers. The IC group had
      significantly more WMH score in comparison with the other groups after
      controlling age. The linear regression analysis showed that age was the factor
      most strongly associated with the total score of WMH; and the location of
      stenosis was positively related to WMH, especially in deep white matter. Our data
      show that IC stenosis is associated with WMH, indicating that IC stenosis, rather
      than EC stenosis, is likely to cause white matter lesions. These findings raise
      the possibility that occlusion of penetrating arteries, embolism to border-zone
      areas and a hemodynamic mechanism associated with IC stenosis leads to the
      formation of white matter lesions.

PMID- 20800911
TI  - Activation of matrix metalloproteinase-9 is associated with mobilization of bone
      marrow-derived cells after coronary stent implantation.
AB  - BACKGROUND: After stent-related vascular injury, an inflammatory response
      triggers the mobilization of bone marrow-derived stem cells, including both
      endothelial and smooth muscle progenitors, leading to re-endothelialization as
      well as restenosis. It has been postulated that neutrophil-released matrix
      metalloproteinase-9 (MMP-9) induces stem cell mobilization. AIM: To elucidate the
      mechanistic link between inflammation and stem cell mobilization after coronary
      stenting. METHODS: In 31 patients undergoing coronary stenting, we serially
      measured activated Mac-1 on the surface of neutrophils and active MMP-9 levels in
      the coronary sinus blood plasma, and the number of circulating CD34-positive
      cells in the peripheral blood. RESULTS: After bare-metal stent implantation
      (n=21), significant increases in the numbers of CD34-positive cells (maximum on
      post-procedure day 7, P<0.001), activated Mac-1 (at 48 h, P<0.001), and active
      MMP-9 levels (at 24h, P<0.001) were observed. However, these changes were absent
      after sirolimus-eluting stent implantation (n=10). In overall patients, the
      numbers of CD34-positive cells on day 7 (R=0.58, P<0.01) and activated Mac-1 at
      48 h (R=0.58, P<0.01) were both correlated with active MMP-9 levels at 24h.
      Stimulation of activated Mac-1 on the surface of isolated human neutrophils
      produced active MMP-9 release in vitro. CONCLUSIONS: These results suggest that
      stent-induced activation of Mac-1 on the surface of neutrophils might trigger
      their MMP-9 release, possibly leading to the mobilization of bone marrow-derived
      stem cells. These reactions were substantially inhibited by sirolimus-eluting
      stents.

PMID- 20800912
TI  - EEG correlates of postural audio-biofeedback.
AB  - The control of postural sway depends on the dynamic integration of multi-sensory
      information in the central nervous system. Augmentation of sensory information,
      such as during auditory biofeedback (ABF) of the trunk acceleration, has been
      shown to improve postural control. By means of quantitative
      electroencephalography (EEG), we examined the basic processes in the brain that
      are involved in the perception and cognition of auditory signals used for ABF.
      ABF and Fake ABF (FAKE) auditory stimulations were delivered to 10 healthy naive
      participants during quiet standing postural tasks, with eyes-open and closed.
      Trunk acceleration and 19-channels EEG were recorded at the same time. Advanced,
      state-of-the-art EEG analysis and modeling methods were employed to assess the
      possibly differential, functional activation, and localization of EEG spectral
      features (power in alpha, beta, and gamma bands) between the FAKE and the ABF
      conditions, for both the eyes-open and the eyes-closed tasks. Participants gained
      advantage by ABF in reducing their postural sway, as measured by a reduction of
      the root mean square of trunk acceleration during the ABF compared to the FAKE
      condition. Population-wise localization analysis performed on the comparison FAKE
      - ABF revealed: (i) a significant decrease of alpha power in the right inferior
      parietal cortex for the eyes-open task; (ii) a significant increase of gamma
      power in left temporo-parietal areas for the eyes-closed task; (iii) a
      significant increase of gamma power in the left temporo-occipital areas in the
      eyes-open task. EEG outcomes supported the idea that ABF for postural control
      heavily modulates (increases) the cortical activation in healthy participants.
      The sites showing the higher ABF-related modulation are among the known cortical
      areas associated with multi-sensory, perceptual integration, and sensorimotor
      integration, showing a differential activation between the eyes-open and eyes
      closed conditions.

PMID- 20800913
TI  - Comparative analyses of rider position according to skill levels during walk and
      trot in Jeju horse.
AB  - The purpose of this study was to evaluate the rider position at walk and trot as
      a function of rider skill level by analyzing joint angles. Participants included
      three advanced riders and six beginners, and training was conducted for one hour,
      twice a week for 24 weeks. In the walk stage of the beginners' group, the elbows
      and shoulders sustained postures comparable to those of the advanced riders
      group; the trunk tilted forwards at first, but later it tilted slightly behind
      the vertical. The knee, ankle, and left-right angle kept stable postures after 12
      weeks of training (p<.05). The front-rear (FR) angle of the beginners group
      improved during training, but it was still lower than the advanced riders group
      after 24 weeks of training (p<.05). At trot, while the knee angle measurement of
      the beginners' group was similar to the advanced riders, the ankle joint
      sustained a forward point posture. The ankle joint maintained dorsiflexion
      posture with 83.9 degrees +/-5.3 in the advanced riders group, while the
      beginners group had plantar flexion posture with 98.7 degrees +/-6.0. This study
      suggested that the correlation between the joint and body segment angles could be
      an important indicator in the evaluation of rider proficiency.

PMID- 20800914
TI  - Influence of swimming speed on inter-arm coordination in competitive unilateral
      arm amputee front crawl swimmers.
AB  - This study examined the effect of swimming speed on inter-arm coordination and
      the inter-relationships between swimming speed, inter-arm coordination, and other
      stroke parameters, in a group of competitive unilateral arm amputee front crawl
      swimmers. Thirteen highly-trained swimmers were filmed underwater during a series
      of 25-m front crawl trials of increasing speed. Arm coordination for both arms
      was quantified using an adapted version of the Index of Coordination. Inter-arm
      coordination of the amputee swimmers did not change as swimming speed was
      increased up to maximum. Swimmers showed significantly more catch-up coordination
      of their affected-arm compared to their unaffected-arm. When sprinting, the
      fastest swimmers used higher stroke frequencies and less catch-up of their
      affected-arm than the slower swimmers. Unilateral arm-amputees used an
      asymmetrical strategy for coordinating their affected-arm relative to their
      unaffected-arm to maintain the stable repetition of their overall arm stroke
      cycle. When sprinting, the attainment of a high stroke frequency is influenced
      mainly by the length of time the affected-arm is held in a stationary position in
      front of the body before pulling. Reducing this time delay appears to be
      beneficial for successful swimming performance.

PMID- 20800915
TI  - Assessment of postural control in patients with Parkinson's disease: sway ratio
      analysis.
AB  - Analysis of the postural stability impairments in neurodegenerative diseases is a
      very demanding task. Age-related declines in posturographic indices are usually
      superimposed on effects associated with the pathology and its treatment. We
      present the results of a novel postural sway ratio (SR) analysis in patients with
      Parkinson's disease (PD) and age-matched healthy subjects. The sway ratios have
      been assessed based upon center of foot-pressure (CP) signals recorded in 55
      parkinsonians (Hoehn and Yahr: 1-3) and 55 age-matched healthy volunteers while
      standing quiet with eyes open (EO) and then with eyes closed (EC). Complementing
      classical sway measure abnormalities, the SR exhibited a high discriminative
      power for all controlled factors: pathology, vision, and direction of sway. Both
      the anteroposterior (AP) and mediolateral (ML) sway ratios were significantly
      increased in PD patients when compared to the control group. An additional SR
      increase was observed in the response to eyes closure. The sway ratio changes
      documented here can be attributed to a progressive decline of a postural
      stability control due to pathology. In fact, a significant correlation between
      the mediolateral SR under EO conditions and Motor Exam (section III) score of the
      UPDRS was found. The mediolateral sway ratios computed for EO and EC conditions
      significantly correlated with the CP path length (r = .87) and the mean
      anteroposterior CP position within the base of support (r = .38). Both indices
      reflect postural stability decline and fall tendency # in parkinsonians. The
      tremor-type PD patients (N=34) showed more pronounced relationships between the
      mediolateral SR and selected items from the UPDRS scale, including: falls
      (Kendall Tau=.47, p < .05), rigidity (.45, p < .05), postural stability
      (retropulsion) (.52), and the Motor Exam score (.73). The anteroposterior SR
      correlated only with tremor (Kendal Tau = .77, p < .05). It seems that in force
      plate posturography the SR can be recommended as a single reliable measure that
      allows for a better quantitative assessment of postural stability impairments.

PMID- 20800916
TI  - Movement duration does not affect automatic online control.
AB  - Pisella et al. (2000) have shown that fast aiming movements are automatically
      modified on-line in response to a change in target position. Specifically, when a
      movement is less than 300ms in duration the reach is completed to a target's new
      location even when one never intended to respond to the target jump. In contrast,
      when movements are slower, the reach is completed according to instructions. At
      present, it is unclear if it is possible for one's intentions to guide the
      initial stages of these slow movements. To determine if the intentional control
      mechanism can guide the initial stages of a slow aiming movement, participants
      aimed to targets that could jump at movement onset, with a slow and very slow
      movement time goal. In particular, participants were to point towards ("pro
      point") or away from ("anti-point") the target jump, with a movement time goal of
      500 or 1200ms. Results showed that in the anti-point condition, movement
      trajectories first deviated in the same direction as the target jump, followed by
      a response in the intended (opposite) direction. This suggests that while
      movement outcome is controlled by the intentional system, even in these slow
      aiming movements the automatic system is engaged at movement onset.

PMID- 20800917
TI  - Evaluation of Bacillus strains as model systems for the work on Bacillus
      anthracis spores.
AB  - Available strain collections of Bacillus anthracis and Bacillus cereus were
      screened for B. cereus strains sharing major genotypic characteristics with B.
      anthracis. Based on the comparison of partial spoIIIAB sequences, whole genome
      sequences and MLST, a strain set representing different lineages including
      candidate model strains for B. anthracis was compiled. Spores from the selected
      strain set and two B. anthracis strains were prepared according to a newly
      optimized protocol transferable to biosafety level-3 (BSL3) conditions and
      phenotypic characteristics including scanning electron microscopy (SEM), heat
      inactivation, and germination were evaluated. Two B. cereus isolates were
      identified that were genetically related to B. anthracis and showed high
      similarity to B. anthracis spores in their heat inactivation profile and their
      response to the germinants l-alanine and inosine. In addition, these isolates
      were also mimicking B. anthracis on modified PLET, a selective plating medium for
      B. anthracis, and shared various other biochemical characteristics with B.
      anthracis. Therefore these two strains are not only appropriate models for B.
      anthracis in experiments based on spore characteristics but also in trials
      working with plating media. These two strains are now used within the BIOTRACER
      consortium as validated models for B. anthracis and will facilitate the
      development and optimization of tracing and detection systems for B. anthracis in
      the food and feed chain.

PMID- 20800918
TI  - Evaluation of Penicillium expansum isolates for aggressiveness, growth and
      patulin accumulation in usual and less common fruit hosts.
AB  - Experiments were carried out in vivo and in vitro with four isolates of
      Penicillium expansum (I 1, E 11, C 28 and I 12) to evaluate their aggressiveness,
      growth and patulin accumulation in both usual (pears and apples) and less common
      hosts (apricots, peaches, strawberries and kiwifruits) of the pathogen. The 75%
      of isolates showed the ability to cause blue mould in all tested hosts. In
      particular, C 28 and I 1 were the most and the least aggressive isolates,
      respectively (52.9 and 10.6% infection and 20.7 and 15.4 mm lesion diameters).
      'Candonga' strawberries and 'Pinkcot' apricots showed the largest lesion
      diameters (29.8 and 25.3 mm), followed by 'Conference' pears, 'Spring Crest'
      peaches and 'Abate Fetel' pears. With the exception of 'Candonga' strawberries,
      the formation of colonies and mycelial growth of P. expansum isolates on fruit
      puree agar media (PAMs) was stimulated in comparison to a standard growth medium
      (malt extract agar, MEA). Two of the most aggressive isolates in our assays (I 12
      and C 28) showed the greatest accumulation of patulin both in vitro and in vivo,
      while the least aggressive isolate (I 1) produced patulin only in a few growth
      media and cvs. Patulin concentration on fruit PAMs was higher than patulin
      detected in infected fruit tissues. Apple PAMs were the more favorable substrates
      for patulin accumulation in vitro (maximum concentration 173.1 and 74.1 MUg/mL in
      'Pink Lady and 'Golden Delicious' PAMs, respectively) and 'Pink Lady' apples
      inoculated with the isolate E 11 showed the greatest accumulation of patulin in
      the whole in vivo assay (33.9 MUg/mL). However, infected tissue of cv Golden
      Delicious showed lower average accumulation of patulin (1.7 MUg/mL) than that of
      cv Pink Lady (19.1 MUg/mL), and no significant differences in patulin
      concentrations were found among 'Golden Delicious' apples and tested cvs of
      pears, kiwifruits and strawberries. Peaches were highly susceptible to patulin
      accumulation, showing average concentrations of 27.4 and 18.6 MUg/mL in vitro and
      in vivo, respectively. Apricots were also consistently positive for patulin
      accumulation, both in vitro (average values of 20.1 MUg/mL) and in vivo (average
      values of 9.4 MUg/mL). Our study showed the potential of some less common hosts
      of P. expansum (in particular peaches and apricots) to support patulin
      production, indicating that a steady monitoring of patulin contamination should
      be carried out in fruit substrates other than apples and pears.

PMID- 20800919
TI  - Outcome of chronic delta hepatitis in Italy: a long-term cohort study.
AB  - BACKGROUND & AIMS: To investigate the impact of HDV infection on morbidity and
      mortality of patients. PATIENTS AND METHODS: This was a retrospective study on
      188 patients that underwent a program of periodic surveillance until 2008. The
      demographic data, stage of liver disease, treatment efficacy, development of
      liver complications (ascites, oesophageal bleeding, encephalopathy), and survival
      were registered. A Cox regression analysis was carried out to determine the
      impact of viral and patient features on survival. RESULTS: At baseline, 126
      patients (67%) tested positive for serum IgM anti-HDV antibodies, 171 (91%) for
      anti-HBe, 175 (93%) for serum HDV-RNA, and 61 (33%) for serum HBV-DNA. Eighty-two
      patients (43%) had chronic hepatitis at histology; the remaining 106 individuals
      had a clinical/histological diagnosis of cirrhosis. Ninety-six patients received
      interferon (n = 90) or lamivudine (n = 6) therapy, and 27 of them (30%) attained
      a sustained response. During follow up, 21 patients with chronic hepatitis
      progressed to cirrhosis. Of the 127 cirrhotic patients, hepatic decompensation
      occurred in 42 patients (33%) and hepatocellular carcinoma in 17 (13%). The 5-
      and 10-year survival free of events were 96.8% and 81.9%, respectively, for
      patients with chronic hepatitis, and 83.9% and 59.4% for cirrhotics (p<0.01). At
      multivariate analysis, lack of antiviral therapy (p = 0.01), cirrhosis at
      presentation (p<0.01), and male sex (p = 0.03) independently predicted a worse
      outcome. CONCLUSION: HDV liver disease lasts several decades. Half of all
      patients who develop cirrhosis later will advance to liver failure. At present,
      interferon therapy is recommended as soon as possible to slow or alter the
      natural course of liver disease.

PMID- 20800921
TI  - Human leucocyte antigen class II genotype in susceptibility and resistance to co
      amoxiclav-induced liver injury.
AB  - BACKGROUND & AIMS: Co-amoxiclav is one of the most common causes of drug-induced
      liver injury (DILI). Although there are previous reports of genetic associations
      between HLA class II and co-amoxiclav-related DILI, studies to date have been
      based on very small numbers from single centres only. In order to address this
      problem we have investigated the role of HLA class II DRB1 and DQB1 in 61 cases
      of co-amoxiclav DILI as part of a UK-wide multicentre study. METHODS: HLA alleles
      and genotypes were compared with those of 40 individuals exposed to co-amoxiclav
      without toxicity (treated controls) and 191 population controls. RESULTS: There
      were two significant findings from the study. First, HLA-DRB1*15 was increased in
      patients (53%) versus both treated (33%: OR=2.29: 95% CI: 1.00-5.26) and
      population controls (30%: OR=2.59:95% CI: 1.44-4.68: p=0.002). Second, DRB1*07
      was found to be reduced in patients (9.8%) compared to both treated (35%:
      OR=0.18: 95% CI: 0.06-0.52: p=0.0011, pc=0.0154) and population controls (29%:
      OR=0.266: 95% CI: 0.11-0.65: p=0.0019, pc=0.0266). CONCLUSIONS: These results
      confirm the previously reported significant genetic risk for HLA-DRB1*15 and also
      provide evidence of a protective effect of the HLA-DRB1*07 family of alleles. HLA
      alleles and haplotypes may be particularly important in susceptibility and
      resistance to co-amoxiclav-DILI, but it remains to be seen whether this effect is
      due to the identified alleles or others in close linkage disequilibrium elsewhere
      on the MHC.

PMID- 20800922
TI  - HLA class I allele associations with HCV genetic variants in patients with
      chronic HCV genotypes 1a or 1b infection.
AB  - BACKGROUND & AIMS: The adaptive immune response against hepatitis C virus (HCV)
      is significantly shaped by the host's composition of HLA-alleles with the
      consequence that the HLA phenotype is a critical determinant of viral evolution
      during adaptive immune pressure. In the present study, we aimed to identify
      associations of HLA class I alleles with HCV subtypes 1a and 1b genetic variants.
      METHODS: The association between HCV genetic variants and specific HLA-alleles
      was investigated in a cohort of 159 patients with chronic HCV genotypes 1a- and
      1b-infection who were treated with pegylated interferon-alfa 2b and ribavirin in
      a prospective controlled trial for 48 weeks by direct sequencing of the genes
      encoding the HCV proteins E2, NS3, and NS5B and by HLA class I-genotyping of
      patients. HCV genetic variants were associated with specific HLA-alleles and the
      binding strength of accordant amino acid sequences to the corresponding HLA
      allele was assessed by using the SYFPEITHI-algorithm. RESULTS: Overall,
      associations between HLA class I alleles and HCV sequence variation were rare.
      Five unknown HLA class I-associated viral genetic variations were identified,
      which in part affected the binding of predicted HCV CD8+ T cell epitopes to the
      respective HLA-allele. In addition, different patterns of HLA class I-allele/HCV
      sequence associations between the two subtypes were observed. CONCLUSIONS: We
      identified several unknown HLA class I-restricted HCV variants which in part
      impair binding to predicted HCV CD8+ T cell epitopes with remarkable differences
      between HCV subtypes 1a and 1b quasispecies.

PMID- 20800923
TI  - Inactivation of extrahepatic vascular Akt improves systemic hemodynamics and
      sodium excretion in cirrhotic rats.
AB  - BACKGROUND & AIMS: Increased activity of the vascular Akt/eNOS signaling pathway
      is involved in the hemodynamic and renal complications developed by patients and
      rats with cirrhosis and ascites. This occurs in the setting of impaired Akt/eNOS
      activity within the cirrhotic liver. Here we assessed the feasibility of
      selectively inhibiting vascular eNOS without further impairing the intrahepatic
      activity of this enzyme. Ultimately, we sought to determine whether endothelial
      transduction of a constitutively inactive mutant of Akt (AA-Akt) improves
      circulatory function and sodium excretion in cirrhotic rats with ascites.
      METHODS: First, we administered recombinant adenoviruses that encode the beta
      galactosidase gene (beta-gal) to 5 control rats and 5 cirrhotic rats with ascites
      and analyzed their tissue distribution by chemiluminescence. Next, urine samples
      were obtained from 18 cirrhotic rats with ascites and then the animal randomly
      received saline or adenoviruses containing the beta-gal or the AA-Akt genes.
      Following a 24-h urine collection period, hemodynamic studies were performed and
      tissue samples were obtained to analyze Akt and eNOS expressions. RESULTS: No
      beta-gal activity was detected in the liver of cirrhotic rats compared to that of
      controls. This was paralleled by increased beta-gal activity in other territories
      such as the thoracic aorta. AA-Akt transduction improved systemic hemodynamics,
      splanchnic perfusion pressure and renal excretory function in comparison with
      cirrhotic rats transduced with beta-gal adenoviruses or receiving saline.
      Moreover, the AA-Akt transgene did not modify portal pressure. CONCLUSIONS:
      Inactivation of extrahepatic vascular Akt and the concomitant decrease in nitric
      oxide expression ameliorate systemic hemodynamics and renal excretory function in
      experimental cirrhosis.

PMID- 20800924
TI  - The independent effects of fatigue and UDCA therapy on mortality in primary
      biliary cirrhosis: results of a 9 year follow-up.
AB  - BACKGROUND & AIMS: Long-term outcome in primary biliary cirrhosis (PBC) remains
      unclear. Whilst response to ursodeoxycholic acid (UDCA) is associated with good
      outcome, this effect is not universal. Early data from our group have suggested
      that one factor associated with a poorer outcome in PBC is fatigue. The aim of
      this study was to explore the inter-relationship between UDCA use, response, and
      fatigue in determining outcome over 9 years in a unique, comprehensive patient
      cohort. METHODS: Longitudinal prospective study of a geographically-defined
      complete cohort of PBC patients in North-East England and matched community
      controls. RESULTS: Survival to death or transplant was significantly lower in PBC
      patients than in the case-control population (88/136 (65%) v 114/136 84% (p<0.001
      by log-rank test), with better survival in UDCA responders (defined using the
      Paris criteria) than in patients not treated with UDCA at study outset. Compared
      to the whole control group survival was reduced in PBC patients fatigued at study
      outset but not in those without fatigue (p<0.0001); an effect independent of the
      beneficial effect of UDCA response and of conventional parameters of liver
      disease severity. UDCA responders without fatigue at the study outset had a 9
      year survival which was identical to controls. Patients without fatigue at the
      study outset who developed fatigue during follow-up had significantly worse
      survival than patients who remained without fatigue throughout (p<0.05). Fatigued
      controls had worse survival than non-fatigued controls (p = 0.05). CONCLUSIONS:
      Survival in a comprehensive cohort of PBC patients is substantially reduced
      compared with case-matched community controls. Development of fatigue and non
      treatment with UDCA were specifically (and independently) associated with
      increased risk of death in PBC.

PMID- 20800925
TI  - Brain hypoxanthine concentration correlates to lactate/pyruvate ratio but not
      intracranial pressure in patients with acute liver failure.
AB  - BACKGROUND & AIMS: The pathogenesis of cerebral edema in acute liver failure is
      suggested, in in vitro and animal studies, to involve a compromised oxidative
      metabolism with a decrease in cerebral ATP levels and an increase in purine
      concentrations. In this study we hypothesize that the cerebral concentrations of
      hypoxanthine, inosine, and lactate/pyruvate (LP) ratio are increased and
      correlated in patients with acute liver failure. Furthermore, we expect the
      purines and L/P ratio to correlate with intracranial pressure (ICP) (positively),
      and cerebral perfusion pressure (CPP) (negatively). METHODS: In 17 patients (aged
      18-60 years) with acute liver failure and severe hyperammonemia (182 +/- 36 MUM
      (mean +/- SD)), cerebral microdialysis was performed, and ICP and CPP were
      monitored. Microdialysate concentrations of hypoxanthine, inosine, lactate, and
      pyruvate were measured. RESULTS: The hypoxanthine concentration was 23.0 +/- 12
      MUM in early samples and 11.7 +/- 6.8 MUM in late samples (normal level ~2.0
      MUM). The inosine concentration was 7.2 +/- 7.1 MUM and 2.8 +/- 1.6 MUM, and the
      LP ratio was 55.8 +/- 21.6 and 45.6 +/- 20.8, respectively (normal level ~18).
      Hypoxanthine correlated significantly to LP ratio (r(2)=0.40, p<0.01) while
      inosine did not. The purine levels and L/P ratio did not correlate to ICP or CPP,
      nor did they differ between patients with high ICP (>20 mmHg, n=9) and patients
      without (n=8). CONCLUSIONS: This study shows that the high cerebral LP ratio
      correlates to the hypoxanthine level in patients with acute liver failure.
      However, these metabolic alterations were not related to the development of
      intracranial hypertension.

PMID- 20800920
TI  - Management and treatment of chronic hepatitis B virus infection in HIV positive
      and negative patients: the EPIB 2008 study.
AB  - BACKGROUND & AIMS: To compare the management and the virological and serological
      efficacy of treatments for chronic hepatitis B (CHB) in HIV positive and negative
      patients. METHODS: Two hundred and forty-six HIV positive and 205 HIV negative
      consecutive patients with past or present CHB, seen in October 2008 in
      participating departments, were included in a multicenter study. All the data
      were retrospectively collected from the first visit to October 2008 through a
      standardized questionnaire. RESULTS: Compared to HIV negative patients, HIV
      positive patients more often presented positive HBeAg (46.4% vs. 32.8%, p=0.01),
      HBV genotype A (54.8% vs. 17.1%, p<0.0001), co-infection with HCV (12.4% vs.
      5.9%, p=0.0002) or HDV (12.6% vs. 2.9%, p=0.04). HIV positive patients were more
      often on HBV therapy (92.7% vs. 57.1%, p<0.0001), leading to undetectable serum
      HBV DNA levels (71.0% vs. 44.1%, p<0.0001). In HIV positive patients,
      multivariate analysis showed that older age, lower initial HBV DNA levels, and
      longer time on HBV therapy significantly correlated with undetectable HBV DNA. No
      difference in efficacy was observed between tenofovir used alone or in
      combination. HBsAg (but not HBe) loss was more often observed in HIV positive
      patients, sometimes followed by HBsAg re-appearance after withdrawal of HBV
      treatment. Excluding the 37 HBV-HCV-co-infected patients, the last clinical
      presentation and liver fibrosis scores were similar in HIV positive and negative
      patients. CONCLUSIONS: The assessment of CHB and the efficacy of HBV therapy have
      improved in HIV positive patients. HIV infection did not have a negative impact
      on the likelihood of HBV therapeutic success.

PMID- 20800926
TI  - Intrahepatic angiogenesis and sinusoidal remodeling in chronic liver disease: new
      targets for the treatment of portal hypertension?
AB  - Portal hypertension accounts for the majority of morbidity and mortality that is
      encountered in patients with cirrhosis. Portal hypertension is initiated in large
      part through increases in intrahepatic vascular resistance. Fibrosis,
      regenerative nodule formation, and intrahepatic vasoconstriction are classical
      mechanisms that account for increased intrahepatic vascular resistance in
      cirrhosis. Recent data suggest that intrahepatic angiogenesis and sinusoidal
      remodeling could also be involved in sinusoidal resistance, fibrosis, and portal
      hypertension. While angiogenesis is defined as the formation of new vessels
      deriving from existing ones, sinusoidal remodeling in its pathological form
      associated with cirrhosis is characterized by increased mural coverage of vessels
      by contractile HSC. Most attention on the mechanisms of these processes has
      focused on the liver sinusoidal endothelial cell (SEC), the hepatic stellate cell
      (HSC), and the paracrine signaling pathways between these two cell types.
      Interventions that target these vascular structural changes have beneficial
      effects on portal hypertension and fibrosis in some animal studies which has
      stimulated interest for pursuing parallel studies in humans with portal
      hypertension.

PMID- 20800927
TI  - Enhancing community system in China's recent health reform: An effort to improve
      equity in essential health care.
AB  - OBJECTS: This article reviews China's policy development on community health
      centers and examines effects on service selection, due to difference in funding
      level and profit seeking incentive. METHODS: We summarize policies on community
      health centers since 1997 and identify the importance of joint action from seven
      government agencies in 2006. Using survey data in 2006 and 2007 from two cities
      with different financing capability and management strategy, we analyze service
      selection between these cities and before and after a funding policy change.
      RESULTS: With better financing capability (65 vs. 9 Yuan per resident) and a
      government backup for any loss, community centers in city A provide more high
      cost services than city B such as house visits (275 vs. 6 per 10,000 residents)
      and house beds (52 vs. 1 per 10,000 residents). Both services are mostly demanded
      by residents. CONCLUSION: Joint action from related government agencies in 2006
      is critical for the rapid development of community health system in China. With
      less funding, community centers have to restrict high-cost services. There is no
      evidence of shirking after initiating a fully funded financing policy. Economic
      disparity among cities is a major barrier for improving equity in basic health
      care.

PMID- 20800929
TI  - NO (nitric oxide): the ring master.
AB  - The migration and proliferation of endothelial cells affect the process of
      angiogenesis or the formation of blood vessels. Endothelial cells interact with
      each other to form ring-like structures in monolayers and tubular structures in
      matrigels. However, the transit phase between the individual endothelial cells
      and fully formed tubular structures is yet to be established. Guided by imaging,
      Western blot analysis, drug perturbation studies and siRNA studies we validate
      that endothelial ring structures are the fundamental and monomeric units of
      capillary tubes and nitric oxide is implicated in their fabrication. Giving input
      from experimental data, we used bagging classifier and information-gain to
      determine some of the physical and chemical parameters that define these
      biological structures. Further, we elucidated the implications of endothelial
      nitric oxide synthase and the NO/sGC/cGMP pathway in the formation of endothelial
      rings. We conclude that, formation of endothelial ring structure is important for
      angiogenesis and is mediated by the NO/sGC/cGMP pathway; and further endothelial
      rings can be used as in vitro models to study angiogenesis.

PMID- 20800928
TI  - Never mind the length, feel the quality: the impact of long-term epidemiological
      data sets on theory, application and policy.
AB  - Infectious diseases have been a prime testing ground for ecological theory.
      However, the ecological perspective is increasingly recognized as essential in
      epidemiology. Long-term, spatially resolved reliable data on disease incidence
      and the ability to test them using mechanistic models have been critical in this
      cross-fertilization. Here, we review some of the key intellectual developments in
      epidemiology facilitated by long-term data. We identify research frontiers at the
      interface of ecology and epidemiology and their associated data needs.

PMID- 20800930
TI  - Energy dissipation is an essential mechanism to sustain the viability of plants:
      The physiological limits of improved photosynthesis.
AB  - In bright sunlight photosynthetic activity is limited by the enzymatic machinery
      of carbon dioxide assimilation. This supererogation of energy can be easily
      visualized by the significant increases of photosynthetic activity under high
      CO(2) conditions or other metabolic strategies which can increase the carbon flux
      from CO(2) to metabolic pools. However, even under optimal CO(2) conditions
      plants will provide much more NADPH+H(+) and ATP that are required for the actual
      demand, yielding in a metabolic situation, in which no reducible NADP(+) would be
      available. As a consequence, excited chlorophylls can activate oxygen to its
      singlet state or the photosynthetic electrons can be transferred to oxygen,
      producing highly active oxygen species such as the superoxide anion, hydroxyl
      radicals and hydrogen peroxide. All of them can initiate radical chain reactions
      which degrade proteins, pigments, lipids and nucleotides. Therefore, the plants
      have developed protection and repair mechanism to prevent photodamage and to
      maintain the physiological integrity of metabolic apparatus. The first protection
      wall is regulatory energy dissipation on the level of the photosynthetic primary
      reactions by the so-called non-photochemical quenching. This dissipative pathway
      is under the control of the proton gradient generated by the electron flow and
      the xanthophyll cycle. A second protection mechanism is the effective re
      oxidation of the reduction equivalents by so-called "alternative electron
      cycling" which includes the water-water cycle, the photorespiration, the malate
      valve and the action of antioxidants. The third system of defence is the repair
      of damaged components. Therefore, plants do not suffer from energy shortage, but
      instead they have to invest in proteins and cellular components which protect the
      plants from potential damage by the supererogation of energy. Under this premise,
      our understanding and evaluation for certain energy dissipating processes such as
      non-photochemical quenching or photorespiration appear in a quite new
      perspective, especially when discussing strategies to improve the solar energy
      conversion into plant biomass.

PMID- 20800931
TI  - Medical missions: a therapeutic primer.
AB  - Trips abroad to underdeveloped countries for the purpose of providing
      dermatologic care (medical missions), while both exciting and gratifying, require
      planning and forethought. What do I bring? What conditions will I encounter? What
      medications will be available? This paper outlines my experiences on such trips
      over the past 15 years, providing an approach and formulary which facilitates the
      performance of daily medical dermatology clinics.

PMID- 20800932
TI  - [Living arrangements of elderly adults in Catalonia (Spain). The impact of health
      deterioration on residential independence].
AB  - OBJECTIVES: To identify the effect of health deterioration on residential
      dependency. MATERIAL AND METHODS: We performed a cross-sectional analysis of the
      microdata from the Catalan Survey of Health (2006), which features a sample of
      3566 individuals aged 65 and over. A set of socio-demographic (sex, age, marital
      status, educational level and municipality size), as well as health variables
      (self-rated health, BADL and IADL dependency) associated with residential
      dependency are analysed by bivariate and multivariate logistic regression.
      RESULTS: Multivariate analysis shows that age, marital status and health are the
      variables that most affect living arrangements and cohabitation. Among men, being
      aged 80 or over (OR>4), being unmarried or widowed (OR=6.4) and having one or
      more IADL dependencies (OR>2.8) increases the risk of residential dependency.
      Whereas for women being aged 80 and over (OR>4), being unmarried (OR=6.8) or
      widowed (OR=11.8) and having three or more IADL dependencies (OR=2.7) is
      associated with residential dependency. Municipality size and the level of
      education (in the latter case only for men) are also significant determining
      factors (P<0.05). CONCLUSION: Although health deterioration, and especially IADL
      dependency, affects residential dependency, its impact is lower than that of
      socio-demographic variables, such as marital status or age. What is more, health
      has a greater influence on men than women, who live independently until they
      experience great difficulty in coping with their activities of daily living. On
      the other hand, men seem to fall more easily into residential dependency once
      they experience any IADL dependency.

PMID- 20800933
TI  - Synthesis, structural elucidation and DNA-dependant protein kinase and
      antiplatelet studies of 2-amino-[5, 6, 7, 8-mono and 7, 8-di-substituted]-1,3
      benzoxazines.
AB  - A number of new 2-amino-[5, 6, 7 and 8]-O-substituted 1,3-benzoxazines, and 2
      amino 8-methyl-7-O-substituted-1,3-benzoxazines were synthesized. Thirty one new
      compounds were tested for their effect on collagen induced platelet aggregation
      and it was found that the most active compounds were 8-methyl-2-morpholin-4-yl-7
      (pyridin-3-ylmethoxy)-4H-1,3-benzoxazin-4-one 9f and 8-methyl-2-morpholin-4-yl-7
      (pyridin-4-ylmethoxy)-4H-1,3-benzoxazin-4-one 9j with IC(50) = 2 +/- 1.5 and 4 +/
      2 MUM respectively. Inhibition of DNA-PK activity at concentrations of 1.6-4 MUM
      were tested for 9 products 5i, 7a-e and 9b, 9f and 9j.

PMID- 20800934
TI  - Synthesis, anti-inflammatory evaluation and docking studies of some new
      fluorinated fused quinazolines.
AB  - A series of novel 8/10-trifluoromethyl-substituted-imidazo[1,2-c] quinazolines
      have been synthesized and evaluated in vivo (rat paw edema) for their anti
      inflammatory activity and in silico (docking studies) to recognize the
      hypothetical binding motif of the title compounds with the cyclooxygenase
      isoenzymes (COX-1 and COX-2) employing GOLD (CCDC, 4.0.1 version) software. The
      compounds, 9b and 10b, were found to have good anti-inflammatory activity [around
      80% of the standard: indomethacin]. The binding mode of the title compounds has
      been proposed based on the docking studies.

PMID- 20800936
TI  - Interactive effects of metal contamination and pathogenic organisms on the
      introduced marine bivalve Ruditapes philippinarum in European populations.
AB  - In natural environment, marine organisms are concomitantly exposed to pollutants
      and multiple disease agents resulting in detrimental interactions. The present
      study evaluated interactive effects of metal contamination (cadmium) and
      pathogenic organisms (trematode parasites Himasthla elongata and pathogenic
      bacteria Vibrio tapetis) singularly and in combination on the bivalve Ruditapes
      philippinarum, an introduced species to Europe, under laboratory controlled
      conditions. After 7 days, metal bioaccumulation and pathogen load were analyzed
      as well as metallothionein (MT) response and hemocyte concentrations and
      activities. Results showed that infection by opportunistic pathogens affects
      metal accumulation, leading to maximal Cd accumulation in co-infected clams.
      Among stressors only V. tapetis induced significant effects on immune parameters
      whereas a particular interaction "trematode-bacteria" was shown on MT responses.
      Despite low trematode infection in agreement with the resistant status of R.
      philippinarum to these macroparasites, significant interaction with bacteria and
      metal occurred. Such results highlight the necessity of taking pathogens into
      account in ecotoxicological studies.

PMID- 20800937
TI  - The dispatcher's window.

PMID- 20800938
TI  - CD27 expression on lymphocyte and sCD27 levels in children with asthma.
AB  - BACKGROUND: CD27, a lymphocyte specific member of the Tumour Necrosis Factor-
      Receptor (TNF-R) family is expressed on the majority of peripheral blood T cells.
      Activation of T cells via TCR/CD3 induces high CD27 surface expression and
      release of a soluble form (sCD27) of the molecule. sCD27 level increases in
      patients suffering from a variety of chronic inflammatory diseases. In the
      present study we aimed to measure both the serum sCD27 levels and CD27 expression
      on T cells in asthmatic patients, to evaluate the state of this molecule in
      allergic inflammation. METHODS: Forty-three patients with asthma were included in
      to the study. CD27 molecule expression and soluble form of this molecule were
      analysed in atopic asthmatic (n:17) and non-atopic asthmatic (n:13) patients
      receiving inhaled corticosteroid treatment, in asthmatic patients whose treatment
      ceased at least for 6 months (n:13) and healthy control subjects (n:14). RESULTS:
      There were no differences in the expression of CD27 molecule on peripheral blood
      lymphocyte nor in its soluble form sCD27 levels in sera between the atopic
      asthmatic and non-atopic asthmatic patients receiving ICS treatment, treatment
      free asthmatic patients and healthy control subjects. CONCLUSIONS: Neither the
      soluble form of CD27 nor its expression on T cells seem to be a reliable marker
      of atopic or non-atopic asthmatic inflammation.

PMID- 20800939
TI  - Initial investigation of acoustic droplet vaporization for occlusion in canine
      kidney.
AB  - Acoustic droplet vaporization (ADV) shows promise for spatially and temporally
      targeted tissue occlusion. In this study, substantial tissue occlusion was
      achieved in operatively exposed and transcutaneous canine kidneys by generating
      ADV gas bubbles in the renal arteries or segmental arteries. Fifteen canines were
      anesthetized, among which 10 underwent laparotomy to externalize the left kidney
      and five were undisturbed for transcutaneous ADV. The microbubbles were generated
      by phase conversion of perfluoropentane droplets encapsulated in albumin or lipid
      shells in the blood. A 3.5-MHz single-element therapy transducer was aligned with
      an imaging array in a water tank with direct access to the renal artery or a
      segmental artery. In vivo color flow and spectral Doppler imaging were used to
      identify the target arteries. Tone bursts of 1 kHz pulse repetition frequency
      with 0.25% duty cycle vaporized the droplets during bolus passage. Both
      intracardiac (IC) and intravenous (IV) injections repeatedly produced ADV in
      chosen arteries in externalized kidneys, as seen by B-mode imaging. Concurrent
      with this in two cases was the detection by pulse-wave Doppler of blood flow
      reversal, along with a narrowing of the waveform. Localized cortex occlusion was
      achieved with 87% regional flow reduction in one case using IC injections.
      Vaporization from IV injections resulted in a substantial echogenicity increase
      with an average half-life of 8 min per droplet dose. Gas bubbles sufficient to
      produce some shadowing were generated by transcutaneous vaporization of
      intrarenal artery or IV-administered droplets, with a tissue path up to 5.5 cm.

PMID- 20800940
TI  - Acoustic radiation force impulse elastography for chronic liver disease:
      comparison with ultrasound-based scores of experienced radiologists, Child-Pugh
      scores and liver function tests.
AB  - The purpose of our study was to investigate whether acoustic radiation force
      impulse (ARFI) elastography provides better diagnostic performance for diagnosis
      of chronic liver disease and correlates better with Child-Pugh scores and liver
      function tests, compared with an ultrasound (US) scoring system based on visual
      assessment of conventional B-mode US images by experienced radiologists. Five
      hundred and twenty-one patients with clinically proven chronic liver disease (n =
      293), fatty liver (n = 95) or normal liver (n = 133) were included in this study.
      B-mode liver US and ARFI elastography were performed in all patients. ARFI
      elastography was performed at least five times, with each measurement obtained at
      a different area of the right hepatic lobe; mean shear wave velocity (SWV) was
      calculated for each patient. The mean SWV was compared with US-based scores from
      two radiologists (based on liver surface nodularity, parenchyma echotexture and
      hepatic vein contour), Child-Pugh scores and liver function tests. The mean SWV
      of the normal liver group was 1.08 m/s +/- 0.15; of the fatty liver group, 1.02
      m/s +/- 0.16; and of the chronic liver disease group, 1.66 m/s +/- 0.60 (p <
      0.001). The area under the receiver operating characteristics curve of the mean
      SWV in ARFI elastography was significantly higher than that of the conventional B
      mode US-based scores by two radiologists (0.89 vs. 0.74 and 0.77, p < 0.05), with
      a sensitivity of 75.4% and a specificity of 89.5% at the cut-off value of 1.22
      m/s. The sensitivity of the mean SWV was significantly higher than the US-based
      scores (p < 0.001), although the specificity was not (p > 0.05). The mean SWV was
      better correlated with Child-Pugh scores and all liver function tests (except
      total protein) than the US-based scores from two radiologists. In conclusion,
      ARFI elastography showed better diagnostic performance than visual assessment of
      experienced radiologists for diagnosis of chronic liver disease, as well as for
      evaluation of the severity of chronic liver disease.

PMID- 20800941
TI  - Real-time qualitative ultrasound elastography of miscellaneous non-nodal neck
      masses: applications and limitations.
AB  - To evaluate real-time qualitative ultrasound elastography as an adjunct to
      conventional sonography for evaluation of non-nodal neck masses identified in
      routine clinical practice, 52 consecutive masses in 49 patients underwent both
      techniques. Lesion stiffness was graded visually on chromatic-scale elastograms
      from ES0-3 (low to high). Diagnosis was based on (cyto)pathology (11),
      corroborative cross-sectional imaging (18) or characteristic conventional
      sonography (23). There were 16 lipomas, 15 lymphatic/venous vascular
      malformations (LVVMs), six neurogenic tumours/neuromas, five thyroglossal duct
      cysts (TGCs), five (epi)dermoids, three abscesses, one second-arch branchial
      cleft cyst (BCC), and one soft-tissue metastasis. In general terms, lesion
      stiffness was high (ES2-3) for neurogenic tumours/neuromas, (epi)dermoids and
      metastasis, and low (ES0-1) for lipomas, LVVM, TGCs and BCC. Abscesses displayed
      variable stiffness according to fluid content. Technical limitations and
      artefacts of elastograms were identified. Data from real-time qualitative
      ultrasound elastography may be a useful adjunct to sonography for diagnosis of
      non-nodal neck masses.

PMID- 20800942
TI  - Quantitative assessment of arterial wall biomechanical properties using shear
      wave imaging.
AB  - A new ultrasound-based technique is proposed to assess the arterial stiffness:
      the radiation force of an ultrasonic beam focused on the arterial wall induces a
      transient shear wave (~10 ms) whose propagation is tracked by ultrafast imaging.
      The large and high-frequency content (100 to 1500 Hz) of the induced wave enables
      studying the wave dispersion, which is shown experimentally in vitro and
      numerically to be linked to arterial wall stiffness and geometry. The proposed
      method is applied in vivo. By repeating the acquisition up to 10 times per second
      (theoretical maximal frame rate is ~100 Hz), it is possible to assess in vivo the
      arterial wall elasticity dynamics: shear modulus of a healthy volunteer carotid
      wall is shown to vary strongly during the cardiac cycle and measured to be 130 +/
      15 kPa in systole and 80 +/- 10 kPa in diastole.

PMID- 20800943
TI  - Modelling the propagation of ultrasound in the joint space of a human knee.
AB  - There is strong evidence to support the clinical use of low-intensity pulsed
      ultrasound (LIPUS) to augment fracture healing. A previous experimental study
      showed that ultrasound can propagate in the joint space of a single human
      cadaveric knee. A full experimental investigation of this propagation is not
      possible due to poor reproducibility, the scarcity of human cadaveric tissues and
      the practical difficulties in making ultrasound measurements in the knee. The aim
      of the present work is to investigate whether a computer simulation (Wave2000
      Pro(r); Cyberlogic Inc., New York, NY, USA) can give a good representation of the
      experimental model. The simulations provided a good agreement with the
      experimental data, giving some confidence in the application of this computer
      simulation method as a means of determining whether ultrasound can propagate
      through different anatomical regions where bone is present.

PMID- 20800944
TI  - Comparative study of the topical application of Aloe vera gel, therapeutic
      ultrasound and phonophoresis on the tissue repair in collagenase-induced rat
      tendinitis.
AB  - The aim of our study was to compare topical use of Aloe vera gel, pulsed mode
      ultrasound (US) and Aloe vera phonophoresis on rat paw with collagenase-induced
      tendinitis. Edema size, tensile tendon strength, tendon elasticity, number of
      inflammatory cells and tissue histology were studied at 7 and 14 days after
      tendinitis induction. Pulse mode US parameters were: 1 MHz frequency, 100 Hz
      repetition rate, 10% duty cycle, and 0.5 W/cm(2) intensity, applied for 2 min
      each session. A 0.5 mL of Aloe vera gel at 2% concentration was applied for 2 min
      per session, topically and by phonophoresis. Topical application of Aloe vera gel
      did not show any statistically significant improvement in the inflammatory
      process, whereas phonophoresis enhanced the gel action reducing edema and number
      of inflammatory cells, promoting the rearrangement of collagen fibers and
      promoting also the recovery of the tensile strength and elasticity of the
      inflamed tendon to recover their normal pre-injury status. Results seem to
      indicate that Aloe vera phonophoresis is a promising technique for tendinitis
      treatment, without the adverse effect provoked by systemic anti-inflammatory
      drugs.

PMID- 20800945
TI  - Analysis of in vitro transfection by sonoporation using cationic and neutral
      microbubbles.
AB  - The objective of the study was to examine the role of acoustic power intensity
      and microbubble and plasmid concentrations on transfection efficiency in HEK-293
      cells using a sonoporator with a 1-MHz transducer. A green fluorescent protein
      (GFP) reporter plasmid was delivered in as much as 80% of treated cells, and
      expression of the GFP protein was observed in as much as 75% of cells, using a
      power intensity of 2 W/cm(2) with a 25% duty cycle. In addition, the relative
      transfection abilities of a lipid noncationic and cationic microbubble platform
      were investigated. As a positive control, cells were transfected using
      Lipofectamine reagent. Cell survival and transfection efficiency were inversely
      proportional to acoustic power and microbubble concentration. Our results further
      demonstrated that high-efficiency transfection could be achieved, but at the
      expense of cell loss. Moreover, direct conjugation of plasmid to the microbubble
      did not appear to significantly enhance transfection efficiency under the
      examined conditions, although this strategy may be important for targeted
      transfection in vivo.

PMID- 20800947
TI  - Characterization of single thyroid nodules by contrast-enhanced 3-D ultrasound.
AB  - High-resolution ultrasonography (HRUS) has potentialities in differential
      diagnosis between malignant and benign thyroid lesions, but interpretative
      pitfalls remain and accuracy is still poor. We developed an image processing
      technique for characterizing the intra-nodular vascularization of thyroid
      lesions. Twenty nodules (10 malignant) were analyzed by three-dimensional (3-D)
      contrast-enhanced ultrasound imaging. The 3-D volumes were preprocessed and
      skeletonized. Seven vascular parameters were computed on the skeletons: number of
      vascular trees (NT); vascular density (VD); number of branching nodes (or
      branching points) (NB); mean vessel radius (MR); 2-D (DM) and 3-D (SOAM)
      tortuosity; and inflection count metric (ICM). Results showed that the malignant
      nodules had higher values of NT (83.1 vs. 18.1), VD (00.4 vs. 0.01), NB (1453 vs.
      552), DM (51 vs. 18), ICM (19.9 vs. 8.7) and SOAM (26 vs. 11). Quantification of
      nodular vascularization based on 3-D contrast-enhanced ultrasound and
      skeletonization could help differential diagnosis of thyroid lesions.

PMID- 20800946
TI  - Echocardiographic tissue characterization demonstrates differences in the left
      and right sides of the ventricular septum.
AB  - The left and right ventricular function of the heart are influenced by the
      complex structure of the ventricular septum. The cyclic variation of ultrasonic
      backscatter over the cardiac cycle is known to be sensitive to both structural
      and functional characteristics of the myocardium. The objective of this study was
      to investigate differences in the measured magnitude and normalized delay of
      cyclic variation between the left and right sides of the ventricular septum in
      normal adult subjects (N = 31). The measured mean magnitudes of cyclic variation
      were found to be 4.9 +/- 0.4 dB and 2.4 +/- 0.3 dB (mean +/- SE; p < 0.0001) and
      the corresponding normalized delay values were found to be 0.94 +/- 0.05 and 1.59
      +/- 0.12 (mean +/- SE; p < 0.0001) for the left and right sides, respectively.
      These results show significant differences in the measured magnitude and
      normalized delay of cyclic variation between the left and right sides of the
      ventricular septum in normal subjects that appear consistent with predictions
      based on previously described models of cyclic variation of backscatter and
      reported measurements of transmural differences in strain properties of the
      septum.

PMID- 20800949
TI  - Two-dimensional flow imaging in the carotid bifurcation using a combined speckle
      tracking and phase-shift estimator: a study based on ultrasound simulations and
      in vivo analysis.
AB  - A two-dimensional (2-D) blood velocity estimator is presented combining speckle
      tracking (ST) and phase-shift estimation (PE) to measure lateral (vx) and axial
      (vz) velocities respectively. Estimator properties were assessed in a carotid
      bifurcation using ultrasound simulations based on computational fluid dynamics,
      allowing validation toward a ground truth. Simulation results were supported with
      in vivo data of a healthy carotid. ST and PE estimates were combined as: (1) vx
      from 2D-ST and vz from PE, (2) vx from 2D-ST and vz from PE with aliasing
      correction based on ST and (3) vz from PE and only lateral ST for vx. Regression
      analysis showed a 35% to 77% decrease in standard deviation for vz for PE
      compared with ST. Aliasing correction based on ST improved results but also
      introduced spurious artifacts. A marginal decrease in performance was observed
      when only tracking laterally. Further work will focus on in vivo trials in
      patients with carotid plaques.

PMID- 20800948
TI  - Axial-shear strain imaging for differentiating benign and malignant breast
      masses.
AB  - Axial strain imaging has been utilized for the characterization of breast masses
      for over a decade; however, another important feature namely the shear strain
      distribution around breast masses has only recently been used. In this article,
      we examine the feasibility of utilizing in vivo axial-shear strain imaging for
      differentiating benign from malignant breast masses. Radio-frequency data was
      acquired using a VFX 13-5 linear array transducer on 41 patients using a Siemens
      SONOLINE Antares real-time clinical scanner at the University of Wisconsin Breast
      Cancer Center. Free-hand palpation using deformations of up to 10% was utilized
      to generate axial strain and axial-shear strain images using a two-dimensional
      cross-correlation algorithm from the radio-frequency data loops. Axial-shear
      strain areas normalized to the lesion size, applied strain and lesion strain
      contrast was utilized as a feature for differentiating benign from malignant
      masses. The normalized axial-shear strain area feature estimated on eight
      patients with malignant tumors and 33 patients with fibroadenomas was utilized to
      demonstrate its potential for lesion differentiation. Biopsy results were
      considered the diagnostic standard for comparison. Our results indicate that the
      normalized axial-shear strain area is significantly larger for malignant tumors
      compared with benign masses such as fibroadenomas. Axial-shear strain pixel
      values greater than a specified threshold, including only those with correlation
      coefficient values greater than 0.75, were overlaid on the corresponding B-mode
      image to aid in diagnosis. A scatter plot of the normalized area feature
      demonstrates the feasibility of developing a linear classifier to differentiate
      benign from malignant masses. The area under the receiver operator characteristic
      curve utilizing the normalized axial-shear strain area feature was 0.996,
      demonstrating the potential of this feature to noninvasively differentiate
      between benign and malignant breast masses.

PMID- 20800950
TI  - Jugular venous hemodynamic changes with aging.
AB  - Cerebral venous outflow insufficiency via the internal jugular vein (IJV) is
      associated with several neurological disorders. However, a normal reference set
      of IJV hemodynamic parameters derived from a large, healthy population over a
      wide range of age has, until now, been lacking. Color-coded duplex sonography was
      performed on the IJVs of 349 subjects (55.60 +/- 17.49,16 to 89 y; 167 M/182 F).
      With increasing age, increased lumen area and decreased time-averaged mean
      velocity of bilateral IJV and a decreased proportion of total flow volume,
      drainage in the left IJV were found. The frequency of left jugular venous reflux
      (JVR) also increased with aging. We report IJV hemodynamic parameters across a
      large population, which could be used as a normal reference for clinical and
      research purposes. Furthermore, we found a decreased proportion of venous
      drainage, increased JVR prevalence, dilated lumen and slowed flow velocity in the
      left IJV, all of which suggest increased left IJV outflow impedance with aging.

PMID- 20800952
TI  - The acoustic scatter from single biSphere microbubbles.
AB  - Single microbubble acoustic acquisitions provide information on the behaviour of
      microbubble populations by enabling the generation of large amounts of data.
      Acoustic signals from single polylactide-shelled and albumin coated biSphereTM
      microbubbles have been acquired. The responses observed from a range of incident
      frequencies and acoustic pressures varied in duration. Partial echoes shorter
      than the incident pulse duration have been observed for low frequency pulses of
      sufficient amplitude, suggesting release of gas from bubbles. The results
      presented suggest that the mechanism of scatter from hard shelled agents may be
      shell disruption and gas release, or partly from gas leaking from defected shell
      sites, which has previously not been observed optically. These results can
      provide the basis for improved imaging through optimization of incident pulse
      parameters, with potential benefits to both diagnostic and therapeutic
      techniques.

PMID- 20800953
TI  - Validation of endoscopic ultrasound measured flow rate in the azygos vein using a
      flow phantom.
AB  - Increase in flow rate within the azygos vein may be used as an indicator of the
      degree of liver cirrhosis. The aim of this study was to evaluate the error in
      measurement of flow rate using a commercial endoscopic ultrasound system, using a
      flow phantom that mimicked azygos vein depth, diameter and flow rate. Diameter
      was underestimated in all cases, with an average underestimation of 0.09 cm.
      Maximum velocity was overestimated, by 4 +/- 4% at 50 degrees , 11 +/- 3% at 60
      degrees  and 23 +/- 7% at 70 degrees . The increase in error with beam-vessel
      angle is consistent with the error as arising from geometric spectral broadening.
      Flow was underestimated by amounts up to 33%, and it is noted that the
      overestimation caused by geometric spectral broadening is in part compensated by
      underestimation of diameter. It was concluded that measurement of flow rate using
      a commercially available endoscopic ultrasound system is dependent on the beam
      vessel angle, with errors up to 33% for typical vessel depths, diameter and beam
      vessel angle.

PMID- 20800954
TI  - Perfusion CT and US of colorectal cancer liver metastases: a correlative study of
      two dynamic imaging modalities.
AB  - The purpose of this study was to evaluate the correlation between dynamic
      contrast-enhanced computed tomography (DCE-CT) and first-pass dynamic-contrast
      enhanced ultrasound (DCE-US) of normal appearing liver parenchyma and of
      colorectal cancer liver metastases. Thirty patients with hepatic metastases from
      colorectal cancer underwent DCE-CT and DCE-US. To obtain DCE-US reproducibility
      measurements, double contrast-passages (2 * 2.4 mL SonoVue intravenous) were
      acquired. From several DCE-US-derived perfusion indices, the slope-value scored
      best with a reproducibility concordance correlation coefficient ranging from 0.75
      0.93 and overall highest correlation to DCE-CT-derived variables (r = 0.52 to
      0.73). The DCE-US-based tumor-to-liver perfusion gradient also showed a low test
      retest variability and moderately correlated to DCE-CT (concordance correlation
      coefficient 0.87-0.92; r = 0.57 to 0.59). To conclude, DCE-US-based slope-value
      and tumor-to-liver perfusion gradient correlate best with DCE-CT perfusion
      values. However, both techniques cannot be used interchangeably. DCE-US should be
      restricted for studies in which a considerable change in perfusion is expected
      and for patients with a relatively high tumor blood flow at baseline.

PMID- 20800955
TI  - Contrast-enhanced ultrasound of liver lesions.

PMID- 20800956
TI  - Evaluation of coronary flow velocity reserve in homozygous familial
      hypercholesterolemia by transthoracic Doppler echocardiography and dual-source
      computed tomography.
AB  - Homozygous familial hypercholesterolemia (HoFH) is a rare disorder characterized
      by the early onset of atherosclerosis and usually occurs at the ostia of coronary
      arteries. In this study, we used transthoracic Doppler echocardiography (TTDE) to
      evaluate the dynamic changes of coronary flow in HoFH patients and to detect
      aortic and coronary atherosclerosis by dual-source computed tomography (DSCT). We
      studied 20 HoFH patients (12 females, 8 males, mean age 13.1 +/- 5.3 years, with
      a mean low density lipoprotein (LDL) cholesterol of 583 +/- 113 mg/dL) and 15
      control patients (8 females, 7 males, mean age 15.2 +/- 6.9 years, with a mean
      LDL cholesterol 128 +/- 71 mg/dL) using TTDE and DSCT. None of the patients
      showed evidence of ischemia with standard exercise testing. Though the baseline
      coronary flow was similar between HoFH patients and normal controls, the
      hyperemic flow velocities and, thus, the coronary flow velocity reserve (CFVR)
      were significantly lower in those with HoFH. All HoFH patients had aortic
      plaques, nine of them with the coronary artery ostia simultaneously, who had
      significantly higher LDL-cholesterol and lower CFVR than those without ostia
      plaques. Our data demonstrated that TTDE together with DSCT could be a useful
      noninvasive method for detection of coronary flow dynamics and atherosclerosis
      specifically in HoFH subjects with coronary ostia.

PMID- 20800957
TI  - Transcranial Doppler monitoring in Parkinson's disease: cerebrovascular
      compensation of orthostatic hypotension.
AB  - Despite of precipitous blood pressure falls in Parkinson's Disease (PD) patients,
      they may not experience syncope or postural complaints. Can cerebral blood flow
      regulation explain why orthostatic hypotension (OH) has often no accompanying
      symptoms? In patients with PD and OH (18 asymptomatic; 8 symptomatic), arterial
      blood pressure (ABP) as well as Doppler-detected cerebral blood flow velocity
      (CBFV) in middle and posterior cerebral arteries (MCA and PCA) were monitored
      during head-up tilt and compared with 25 controls and eight non-PD-OH patients.
      Analysis included the transfer function between slow spontaneous pressure and
      flow-oscillations. ABP and CBFV were maintained at significantly higher levels in
      asymptomatic than symptomatic PD-OH (ABP: 85.7 +/- 10.5 vs. 66.9 +/- 12.5%; MCA
      FV: 83.3 +/- 9.3 vs. 66.1 +/- 6.8%; PCA-FV: 84.4 +/- 12.2 vs. 65.9 +/- 9.3% of
      supine). When orthostatic complaints occurred, CBFV depended directly on ABP
      changes (MCA r(2) = 0.64; PCA r(2) = 0.62; both p < 0.05). Despite of a tilt
      induced blood pressure instability in PD-OH, the transfer function parameters did
      not differ from normal [phase: MCA: 46.6 +/- 20.5 degrees ; PCA 39.2 +/- 28.8
      degrees , gain: MCA 2.0 +/- 0.7; PCA 2.9 +/- 1.6)]. Results showed a normal
      autoregulatory response to downward blood pressure shifts in PD. Moreover,
      orthostatic blood pressure instability is compensated equally sufficient in
      anterior and posterior parts of cerebral circulation. Whether in PD patients, OH
      becomes symptomatic rather seems to depend on blood pressure falling below the
      autoregulated range.

PMID- 20800958
TI  - Liver metastases: Sulphur hexafluoride-enhanced ultrasonography for lesion
      detection: a systematic review.
AB  - This is a systematic review to evaluate the accuracy of contrast-enhanced
      ultrasonography (CEUS) performed with "SonoVue" (sulphur hexafluoride) in the
      detection of hepatic metastases. The MEDLINE, EMBASE and COCHRANE Databases were
      searched, regardless of language, for relevant articles published before December
      2009. Two reviewers independently assessed study eligibility using a standardized
      form and methodological quality using the quality assessment of diagnostic
      accuracy studies (QUADAS) Checklist. Sensitivity estimates were calculated on a
      per-patient and/or per-lesion basis. The search for published articles yielded
      718 potentially relevant abstracts. Of these, 14 papers were eligible but only
      three articles fulfilled the inclusion criteria, which comprised a total of 450
      patients (patient sample number: range 12 to 365; cancer prevalence: 14.8 to
      71.2%). Estimated per-patient sensitivity ranged from 79-100%. Although the
      quality assessment of diagnostic accuracy studies checklist showed the papers
      were of good quality, a meta-analysis was not applicable because of the lack of
      eligible studies. In conclusion, CEUS seems to be promising in the detection of
      liver metastases; however, there have not been enough studies to conduct meta
      analysis. Further studies are required before this promising method can be widely
      used.

PMID- 20800960
TI  - Splanchnic arterial blood flow is significantly influenced by breathing
      assessment by duplex-Doppler ultrasound.
AB  - Duplex ultrasound is established for the assessment of mesenteric ischemia but
      potential influences of breathing on mesenteric arterial blood velocity have not
      been investigated so far. In 100 patients without abdominal diseases (39 men; age
      59.4 +/- 18.0 years), peak systolic (PSV), end diastolic velocity (EDV) and
      resistance index (RI) were assessed in the celiac trunk (CT) and the superior
      mesenteric artery (SMA) by Doppler ultrasound during expiration and deep
      inspiration. Expiratory PSVs in the CT and the SMA (153.4 +/- 42.5 and 145.3 +/-
      39.5 cm/s) were significantly higher than inspiratory velocities (135.4 +/- 36.8
      and 131.9 +/- 42.2 cm/s, p < 0.0001 and p = 0.0002), with expiratory PSVs
      exceeding inspiratory PSVs in more than 75% of patients. The mean percentage of
      PSV-variation was 21.5% +/- 15.3% and 24.6% +/- 19.1%, respectively. The study
      demonstrates that breathing may exert considerable periodic effects on splanchnic
      arterial hemodynamics. We, therefore, recommend that to prevent an
      underestimation of arterial stenosis, mesenteric Doppler ultrasound should be
      performed during expiration.

PMID- 20800959
TI  - Theoretical and experimental study on temperature elevation behind ribs caused by
      weakly focused ultrasound.
AB  - Temperature distribution in tissues behind ribs produced by weakly focused
      ultrasound had been calculated using Pennes bioheat equation and the validity of
      the theoretical model was experimentally confirmed in vitro using porcine live.
      We found that the position of the maximum temperature in tissue is strongly
      influenced by the distance between the transducer and ribs, while the gap between
      ribs is the determining factor for the maximum achievable temperature. Within the
      focal length, when the distance between the transducer and ribs increases, the
      maximum temperature increases and its position shifts away from the transducer.
      The rib width has little effect on the position of the maximum temperature but
      affects the achievable peak temperature. Our results provide useful information
      for treating liver cancers using ultrasound induced hyperthermia.

PMID- 20800962
TI  - Broadband reduction of the second harmonic distortion during nonlinear ultrasound
      wave propagation.
AB  - Ultrasound contrast harmonic imaging and detection techniques are hampered by the
      harmonic distortion of the ultrasound wave caused by the nonlinearities of the
      medium. To increase the discrimination between the tissue and ultrasound contrast
      agents at higher harmonics, we investigate a tissue harmonic suppression
      technique. The main attention of the research is the signal that is introduced at
      the source and is constructed out of several discrete frequency components from
      the second harmonic band. Therefore, this method was coined as the multiple
      component second harmonic reduction signal or multiple component SHRS. By
      adjusting the amplitude and phase of discrete components and simultaneously
      propagating multiple component SHRS with the imaging signal, the nonlinear
      distortion of the ultrasound waveform is considerably reduced. Using the
      numerical simulation, the optimal parameters for multiple component SRHS were
      deduced. The simulations results were corroborated in the water tank experiments
      and showed 40 dB reduction with respect to the fundamental, covering up to 75% of
      the entire second harmonic band. In the other series of experiments with the
      clinically used contrast agent, the uniform increase in agent-to-tissue ratio of
      7.4 dB over a relatively large region of imaging was observed. The use of the
      proposed method in the everyday clinical practice can improve discrimination
      between the tissue and the contrast agent in harmonic imaging.

PMID- 20800963
TI  - Calibration of the 1-MHz Sonitron ultrasound system.
AB  - Successful drug and gene delivery across cellular membranes can lead to improved
      therapeutic outcomes. Recent studies have suggested that sonoporation may enhance
      drug and gene delivery across cellular membranes. The enhancement may be a result
      of transient permeation of the membrane from cavitation or microstreaming effects
      of microbubbles exposed to ultrasound. Given limited acoustic pressure
      calibration and beam profile characterization of the Sonitron ultrasound systems
      in cellular bioeffects studies previously published, the objective of this work
      was to calibrate the acoustic output and explore the potential for standing waves
      in a cell-well plate. In this study, three 1-MHz transducers driven by Sonitron
      ultrasound systems, which have been used in a number of sonoporation studies,
      were calibrated. Transducers with 10-mm, 6-mm and 20-mm-diameter apertures
      (Sonitron 1000 and 2000, Rich-Mar, Inola, OK, USA) were calibrated using
      polyvinylidene fluoride (PVDF) needle hydrophones. Axial and transverse beam
      profiles were obtained, and the pressures were measured as a function of Sonitron
      intensity dial setting and duty cycle. The acoustic intensity was calculated and
      compared with the Sonitron intensity dial setting for duty cycles from 10-100%.
      Standing waves caused by reflections from the hydrophone holder were detected for
      each transducer. This observation may also have implications for in vitro
      sonoporation studies. Acoustic field characterization is an important first step
      in understanding the mechanisms of sonoporation and drug delivery across
      biomembranes.

PMID- 20800961
TI  - Reliability and responsiveness of musculoskeletal ultrasound in subjects with and
      without spinal cord injury.
AB  - Rehabilitation after spinal cord injury (SCI) aims to preserve the integrity of
      the paralyzed musculoskeletal system. The suitability of ultrasound (US) for
      delineating training-related muscle/tendon adaptations after SCI is unknown. The
      purpose of this study was to quantify within- and between-operator reliability
      for US and to determine its responsiveness to post-training muscle/tendon
      adaptations in SCI subjects. Two novice operators and one experienced operator
      obtained sonographic images of the vastus lateralis, patellar tendon, soleus, and
      Achilles tendon from seven SCI subjects and 16 controls. For control subjects,
      within-operator concordance (ICC [3,1]) ranged from 0.58 to 0.95 for novice
      operators and exceeded 0.86 for the experienced operator. Between-operator
      concordance (ICC [2,1]) ranged from 0.62 to 0.74. Ultrasound detected muscle
      hypertrophy (p < 0.05) following electrical stimulation training in subjects with
      SCI (responsiveness) but did not detect differences in tendon thickness. These
      error estimates support the utility of US in future post-SCI training studies.

PMID- 20800964
TI  - Careful selection and close monitoring of low-risk prostate cancer patients on
      active surveillance minimizes the need for treatment.
AB  - BACKGROUND: With the advent of prostate-specific antigen (PSA) screening and the
      increase in the number of transrectal ultrasound-guided biopsy cores, there has
      been a dramatic rise in the incidence of low-risk prostate cancer (LRPC). Because
      > 97% of men with LRPC are likely to die of something other than prostate cancer,
      it is critical that patients give thought to whether early curative treatment is
      the only option at diagnosis. OBJECTIVE: To identify a group of men with LRPC who
      may not require initial treatment and monitor them on our active surveillance
      (AS) protocol, to determine the percentage treated and the outcome and to analyze
      the quality-of-life data. DESIGN, SETTING, AND PARTICIPANTS: We defined patients
      eligible for AS as Gleason <= 6, PSA <= 10, and two or fewer biopsy cores with <=
      20% tumor in each core. MEASUREMENTS: Kaplan Meier analysis was used to predict
      the 5-year treatment free survival. Logistic regression determined the predictors
      of treatment. Data on sexual function, continence, and outcome were obtained and
      analyzed. RESULTS AND LIMITATIONS: The AS cohort consisted of 230 patients with a
      mean age of 63.4 yr; 86% remained on AS for a mean follow-up of 44 mo. Thirty-two
      of the 230 patients (14%) were treated for a mean follow-up of 33 mo. Twelve had
      a total prostatectomy (TP). The pathologic stage of these patients was similar to
      initially treated TP patients with LRPC. Fourteen underwent radiation therapy,
      and six underwent androgen-deprivation therapy. Fifty percent of patients had no
      tumor on the first rebiopsy, and only 5% of these patients were subsequently
      treated. PSA doubling time and clinical stage were not predictors of treatment.
      No patient progressed after treatment. Among the AS patients, 30% had
      incontinence, yet < 15% were bothered by it. As measured by the Sexual Health
      Inventory for Men, 49% of patients had, at a minimum, moderate (<= 16) erectile
      dysfunction. CONCLUSIONS: If guidelines for AS are narrowly defined to include
      only patients with Gleason 6, tumor volume <= 20% in one or two biopsy cores, and
      PSA levels <= 10, few patients are likely to require treatment. Progression-free
      survival of those treated is likely to be equivalent to patients with similar
      clinical findings treated at diagnosis.

PMID- 20800965
TI  - Some considerations on atypical cases of Charcot-Marie-Tooth disease and use of
      genetic testing in idiopathic polyneuropathies.

PMID- 20800966
TI  - Thermal modification of activated carbon surface chemistry improves its capacity
      as redox mediator for azo dye reduction.
AB  - The surface chemistry of a commercial AC (AC(0)) was selectively modified,
      without changing significantly its textural properties, by chemical oxidation
      with HNO(3) (AC(HNO3)) and O(2) (AC(O2)), and thermal treatments under H(2)
      (AC(H2)) or N(2) (AC(N2)) flow. The effect of modified AC on anaerobic chemical
      dye reduction was assayed with sulphide at different pH values 5, 7 and 9. Four
      dyes were tested: Acid Orange 7, Reactive Red 2, Mordant Yellow 10 and Direct
      Blue 71. Batch experiments with low amounts of AC (0.1 g L(-1)) demonstrated an
      increase of the first-order reduction rate constants, up to 9-fold, as compared
      with assays without AC. Optimum rates were obtained at pH 5 except for MY10,
      higher at pH 7. In general, rates increased with increasing the pH of point zero
      charge (pH(pzc)), following the trend AC(HNO3) < AC(O2) < AC(0) < AC(N2) <
      AC(H2). The highest reduction rate was obtained for MY10 with AC(H2) at pH 7,
      which corresponded to the double, as compared with non-modified AC. In a
      biological system using granular biomass, AC(H2) also duplicated and increase 4.5
      fold the decolourisation rates of MY10 and RR2, respectively. In this last
      experiment, reaction rate was independent of AC concentration in the tested range
      0.1-0.6 g L(-1).

PMID- 20800967
TI  - Bioventing remediation and ecotoxicity evaluation of phenanthrene-contaminated
      soil.
AB  - The objectives of soil remediation processes are usually based on threshold
      levels of soil contaminants. However, during remediation processes, changes in
      bioavailability and metabolite production can occur, making it necessary to
      incorporate an ecotoxicity assessment to estimate the risk to ecological
      receptors. The evolution of contaminants and soil ecotoxicity of artificially
      phenanthrene-contaminated soil (1000 mg/kg soil) during soil treatment through
      bioventing was studied in this work. Bioventing was performed in glass columns
      containing 5.5 kg of phenanthrene-contaminated soil and uncontaminated natural
      soil over a period of 7 months. Optimum conditions of mineralisation
      (humidity=60% WHC; C/N/P=100:20:1) were determined in a previous work. The
      evolution of oxygen consumption, carbon dioxide production, phenanthrene
      concentration and soil toxicity were studied on sacrificed columns at periods of
      0, 3 and 7 months. Toxicity to soil and aquatic organisms was determined using a
      multispecies system in the soil columns (MS-3). In the optimal bioventing
      treatability test, we obtained a reduction rate in phenanthrene concentration
      higher that 93% after 7 months of treatment. The residual toxicity obtained at
      the end of the treatment was not attributed to the low phenanthrene
      concentration, but to the ammonia used to restore the optimal C/N ratio.

PMID- 20800968
TI  - Prevention of medication overuse in patients with migraine.
AB  - This multi-center study compared the therapeutic effect of a cognitive-behavioral
      minimal contact program (MCT) to the effect of a brochure (bibliotherapy) for the
      prevention of medication overuse headache (MOH) in migraine patients. Seven
      German headache centers recruited 182 migraine patients with high triptan or
      analgesic intake frequency. Patients were randomly allocated to either the MCT
      group, receiving both an MCT program and an educational brochure or to the biblio
      group receiving only the brochure. All participants continued usual medical
      treatment. Course of headaches, intake of analgesics or triptans after training,
      3 months post-training as well as 1-2 years (mean 15.7 months) later and
      psychological variables were defined as outcome variables. A significant decline
      was observed in the number of headache days (11.0-8.8), migraine days (7.3-5.7)
      and medication intake days (7.4-6.1) from pre to post in the MCT-group (p<0.001
      each) and in the biblio-group (p<0.001 each). The pre-to-post-improvements were
      maintained from pre- to short- and from pre- to long-term follow-up (p<0.001
      each) in both groups. Both groups improved significantly from pre to post in
      psychological variables, e.g. pain acceptance: p<0.001; pain catastrophizing:
      p<0.001; functional pain coping: p<0.001; and pain related internal control
      beliefs: p<0.01. Psychological improvements remained stable in both groups at
      short- and long-term follow-up. During the study, none of the patients developed
      an MOH. MCT- and bibliotherapy are useful in migraine patients to prevent
      medication overuse headache or the transition of episodic to chronic headache.

PMID- 20800969
TI  - Increased excitability and spontaneous activity of rat sensory neurons following
      in vitro stimulation of sympathetic fiber sprouts in the isolated dorsal root
      ganglion.
AB  - Many chronic pain conditions including complex regional pain syndrome are
      exacerbated by sympathetic activity. In animal models, sympathetic fibers sprout
      into the dorsal root ganglia (DRG) after peripheral nerve injury, forming
      abnormal connections with sensory neurons. However, functional studies of
      sympathetic-sensory connections have been limited largely to in vivo studies.
      This study describes a new method for studying sympathetic-sensory connections in
      an isolated whole DRG preparation in the rat spinal nerve ligation (SNL) model.
      Three days after ligation of the ventral ramus of the spinal nerve (SNL),
      sympathetic fibers sprouting into the DRG were observed to originate largely in
      the intact dorsal ramus of the spinal nerve, which at the lumbar level is a small
      branch of the spinal nerve separating from the ventral ramus near the
      intervertebral foramen. In whole DRG isolated 3 days after SNL, microelectrode
      recordings of sensory neurons showed that repeated stimulation of the dorsal
      ramus enhanced spontaneous activity in large and medium diameter neurons and
      reduced rheobase in large neurons. These effects, which were slow and long
      lasting, were attributed to stimulation of the sympathetic sprouts because:
      stimulation had no effect in uninjured DRG; and effects could be reduced or
      eliminated by a "cocktail" of antagonists of norepinephrine and ATP receptors, by
      pretreatment with the sympathetic release blocker bretylium, or by pre-cutting
      the grey ramus through which sympathetic fibers coursed to the ligated DRG. The
      latter treatment, a relatively minimal form of sympathectomy, was also highly
      effective in reducing mechanical pain ipsilateral to the SNL.

PMID- 20800970
TI  - In vitro infection of sheep lice (Bovicola ovis Schrank) by Steinernematid and
      Heterorhabditid nematodes.
AB  - Control of sheep lice with conventional pesticides can be compromised by
      difficulty in contacting lice in the dense water repellent fleeces of sheep,
      particularly when sheep have not been recently shorn. Entomopathogenic nematodes
      (ENs) are motile and are able to actively seek out insect hosts. They have
      particular advantages for the control of pests in cryptic habitats, such as the
      fleeces of sheep and avoid many of the problems frequently associated with
      chemical controls. This study investigated whether ENs were able infect and kill
      Bovicola ovis and compared the effectiveness of different species at different
      temperatures and when applied to wool. Four species of nematodes, Steinernema
      carpocapsae, Steinernema riobrave, Steinernema feltiae and Heterorhabditis
      bacteriophora were tested. All were shown to infect and kill lice in Petri dish
      assays at 30 degrees C. At 35 degrees C, the percent infection for S. carpocapsae
      and S. riobrave was significantly higher than for the other two species and
      percent infection by S. feltiae was significantly greater than for H.
      bacteriophora (P<0.05). At 37 degrees C the percent mortality induced by S.
      riobrave was significantly greater than for S. carpocapsae (P<0.05). All species
      were able to locate and infect lice in wool when formulated in water with 8%
      Tween 80. In wool assays the percent lice infected with nematodes was
      significantly greater for S. riobrave than H. bacteriophora at 25 degrees C, but
      there were no other differences between species (P=0.05). S. carpocapsae, S.
      riobrave and S. feltiae caused significantly higher lice mortality than H.
      bacteriophora at both 25 and 35 degrees C in wool assays, but mortality induced
      by the three steinernematid species did not differ significantly (P>0.05). It is
      concluded that of the ENs studied S. riobrave is likely to be most effective
      against B. ovis when applied to live sheep because of its greater tolerance to
      high temperatures and 'cruiser' foraging strategy.

PMID- 20800971
TI  - Effect of Eimeria acervulina infection history on the immune response and
      transmission in broilers.
AB  - Heterogeneity in exposure to Eimeria spp. of chickens in a flock will result in
      differences between individual birds in oocyst output and acquired immunity,
      which subsequently affects transmission of the parasite in the population. The
      aim of this study was to quantify effects of previous infection of broilers with
      Eimeria acervulina on immune responses, oocyst output and transmission. A
      transmission experiment was carried out with pair-wise housed broilers, that
      differed in infection history. This "infection history" was achieved by
      establishment of a primary infection by inoculation of birds with 50,000
      sporulated E. acervulina oocysts at day 6 of age ("primed"); the other birds did
      not receive a primary infection ("naive"). The actual transmission experiment
      started at day 24 of age: one bird (I) was inoculated with 50,000 sporulated
      oocysts and was housed together with a non-inoculated contact bird (C). Oocyst
      excretion and parameters describing transmission, i.e. the number of infected C
      birds and time passed before start of excretion of C birds, were determined from
      day 28 to day 50 for six pairs of four different combinations of I and C birds (I
      C): naive-naive, naive-primed, primed-naive and primed-primed. Immune parameters,
      CD4(+), CD8(+), alphabetaTCR(+) and gammadeltaTCR(+) T cells and macrophages in
      duodenum, were determined in an additional 25 non-primed, non-inoculated control
      birds, and in the naive-naive and naive-primed groups, each group consisting of
      25 pairs. Although the numbers of CD4(+) T cells and gammadeltaTCR(+) T cells
      increased after primary infection, none of the immunological cell types provided
      an indication of differences in infectivity, susceptibility or transmission
      between birds. Oocyst output was significantly reduced in primed I and C birds.
      Transmission was reduced most in the primed-primed group, but nonetheless
      transmission occurred in all groups. This study also showed that acquired
      immunity significantly reduced oocyst output after inoculation and contact
      infection, but not sufficiently to prevent transmission to contact-exposed birds.

PMID- 20800972
TI  - Effect of a calcium-channel blocker (verapamil) on the morphology, cytoskeleton
      and collagenase activity of human skin fibroblasts.
AB  - The effects of verapamil modulating collagen biosynthesis have prompted us to
      study the role of this drug in cultured fibroblasts. In this article, we describe
      the effects of verapamil on fibroblast behaviour, with special emphasis to
      phenotypic modifications, reorganisation of actin filaments and secretion of
      MMP1. Human dermal fibroblasts treated with 50-MUM verapamil changed their normal
      spindle-shaped morphology to stellate. Treated cells showed discrete
      reorganisation of actin filaments, as revealed by fluorescein isothiocyanate
      (FITC)-phalloidin staining and confocal microscopy. We hypothesised that these
      effects would be associated to lower levels of cytosolic Ca(2+). Indeed, short
      time loading with calcium green confirmed that verapamil-treated fibroblasts
      exhibited lower intracellular calcium levels compared to controls. We also
      observed that verapamil increases the secretion of MMP1 in cultured fibroblasts,
      as demonstrated by zymography, specific substrate assays and immunoblot. The
      morphological alterations induced by verapamil are neither cytotoxic nor
      associated with other dramatic cytoskeleton alterations. Thus we may conclude
      that this drug enhances collagenase secretion and does not disrupt the major
      tracks necessary to deliver these enzymes in the extracellular space. The present
      results suggested that verapamil could be used at physiological levels to enhance
      collagen I breakdown, and may be considered a potential candidate for
      intralesional therapy of wound healing and fibrocontractive diseases.

PMID- 20800973
TI  - Reduction of the negative influence of patient motion on quality of CBCT scan.
AB  - The role of cone beam computed tomography (CBCT) in imaging of the oral and
      maxillofacial region is well known and its indications and possibilities are
      still increasing. More sophisticated technologies are being developed each year,
      mainly providing higher resolution, bigger field of view, faster scanning and
      better scatter reduction. One of the major problems remaining to be solved is the
      unwanted movement of the patient during the scanning procedure. All hardware
      solutions that have been developed to fix the patient's head in a steady position
      have their limits. For example, they cannot eliminate small movements caused by
      breathing, heartbeat, and swallowing. We have developed a simple method to
      improve these CBCT images. The movement of the scanned object is monitored with
      marks attached to it. These marks are identified on every 2D image captured
      during the scanning procedure and used to unify the position of these 2D images.
      The final 3D reconstruction produces a sharper 3D data set with higher resolution
      and reduced blur. In conclusion, this simple method has the potential to improve
      the quality of CBCT scans.

PMID- 20800974
TI  - Dorsal pads versus nodules in normal population and Dupuytren's disease patients.
AB  - PURPOSE: There is ambiguity about using the term "knuckle pads" in Dupuytren's
      disease (DD). Clear definitions of dorsal knuckle pads and nodules are lacking
      and the prevalence of these 2 entities has not been determined. We sought to
      define these terms and investigate the distribution and frequency of dorsal
      knuckle pads and dorsal nodules in the normal volunteers and in DD patients.
      METHODS: We assessed 50 consecutive study patients with DD and a convenience
      sample group of 50 control patients without DD for dorsal cutaneous pads (DCP)
      (ie, thickening, sclerosis, and loss of skin elasticity) and dorsal Dupuytren's
      nodules (DDN) (ie, solid tumor-like masses over the digital joints). Demographic
      information was collected for both groups, including the extent of the disease in
      DD patients. We examined both groups for the presence of dorsal lesions and their
      characteristics, and the DD patients for other local and ectopic Dupuytren's
      lesions and for the level of diathesis. RESULTS: None of the control patients had
      DDN, whereas 9 DD patients had DDN (p = .002). Nine control patients had DCP,
      whereas 11 DD patients had DCP (p = .803) Among the 9 control patients with DCP,
      pads were predominantly over the proximal interphalangeal joints and tended to
      occur in men with physically demanding occupations, and in the dominant hand. The
      index and long fingers were most frequently affected. Six patients had only DCP,
      4 had only DDN, and 5 had both DDN and DCP. In the control and study groups, the
      DCP characteristics and patients' demographic data were comparable. Patients with
      DDN were white men with physically undemanding occupations and had lesions over
      the proximal interphalangeal joints, most frequently in the index finger, with an
      average size of 6 mm. Neither DCP nor DDN were encountered in the thumb.
      CONCLUSIONS: Future studies should clearly distinguish between DCP and DDN.
      Although DDN are pathognomonic of DD, DCP demonstrates similar prevalence in
      normal and DD populations.

PMID- 20800975
TI  - Anatomic outcome of percutaneous release among patients with trigger finger.
AB  - PURPOSE: To investigate the adequacy and safety of percutaneous trigger finger
      release on symptomatic patients. METHODS: Two orthopedic non-hand surgeons
      performed percutaneous A1 pulley release on the thumb, index, middle, and ring
      fingers with the use of a 19-gauge needle in 25 fingers of 24 patients. Open
      inspection was then performed to determine the extent of release and any injury
      to the surrounding anatomic structures. RESULTS: Triggering was eliminated in all
      fingers. Of the 25 A1 pulleys, 19 were partially released; only 6 were completely
      released. Noted injury included only superficial abrasions in 15 tendons. None of
      the patients had injury to the digital artery or nerve. CONCLUSIONS: In the
      percutaneous release of trigger fingers, complete anatomic release of the A1
      pulley is not always adequately achieved, even though clinically patients
      experience relief of triggering. It is a safe procedure for the thumb, index,
      middle, and ring fingers as long as the recommended technique is observed.

PMID- 20800976
TI  - Injection drug use cessation and use of North America's first medically
      supervised safer injecting facility.
AB  - BACKGROUND: Vancouver, Canada has a pilot supervised injecting facility (SIF),
      where individuals can inject pre-obtained drugs under the supervision of medical
      staff. There has been concern that the program may facilitate ongoing drug use
      and delay entry into addiction treatment. METHODS: We used Cox regression to
      examine factors associated with the time to the cessation of injecting, for a
      minimum of 6 months, among a random sample of individuals recruited from within
      the Vancouver SIF. In further analyses, we evaluated the time to enrollment in
      addiction treatment. RESULTS: Between December 2003 and June 2006, 1090
      participants were recruited. In Cox regression, factors independently associated
      with drug use cessation included use of methadone maintenance therapy (Adjusted
      Hazard Ratio [AHR] = 1.57 [95% Confidence Interval [CI]: 1.02-2.40]) and other
      addiction treatment (AHR = 1.85 [95% CI: 1.06-3.24]). In subsequent analyses,
      factors independently associated with the initiation of addiction treatment
      included: regular SIF use at baseline (AHR = 1.33 [95% CI: 1.04-1.72]); having
      contact with the addiction counselor within the SIF (AHR = 1.54 [95% CI: 1.13
      2.08]); and Aboriginal ancestry (AHR = 0.66 [95% CI: 0.47-0.92]). CONCLUSIONS:
      While the role of addiction treatment in promoting injection cessation has been
      well described, these data indicate a potential role of SIF in promoting
      increased uptake of addiction treatment and subsequent injection cessation. The
      finding that Aboriginal persons were less likely to enroll in addiction treatment
      is consistent with prior reports and demonstrates the need for novel and
      culturally appropriate drug treatment approaches for this population.

PMID- 20800977
TI  - Self-administration of bretazenil under progressive-ratio schedules: behavioral
      economic analysis of the role intrinsic efficacy plays in the reinforcing effects
      of benzodiazepines.
AB  - Previous research suggests that intrinsic efficacy of benzodiazepines is an
      important determinant of their behavioral effects. We evaluated the reinforcing
      effects of the benzodiazepine partial agonist bretazenil using behavioral
      economic models referred to as "consumer demand" and "labor supply". Four rhesus
      monkeys were trained under a progressive-ratio (PR) schedule of i.v. midazolam
      injection. A range of doses of bretazenil (0.001-0.03 mg/kg/injection and
      vehicle) was evaluated for self-administration with an initial response
      requirement of 40 that doubled to 640; significant self-administration was
      maintained at doses of 0.003-0.03 mg/kg/injection. Next, a dose of bretazenil
      that maintained peak injections/session was made available with initial response
      requirements doubling from 10 to 320 (maximum possible response requirements of
      160 and 5120, respectively), and increasing response requirements decreased self
      administration (mean number of injections/session) of a peak dose (0.01
      mg/kg/injection). Analyses based on consumer demand revealed that a measure of
      reinforcing strength termed "essential value", for bretazenil was similar to that
      previously obtained with midazolam (non-selective full agonist), but less than
      that observed for zolpidem (full agonist, selective for alpha1 subunit-containing
      GABA(A) receptors). According to labor supply analysis, the reinforcing effects
      of bretazenil were influenced by the economic concept referred to as a "price
      effect", similar to our previous findings with midazolam but not zolpidem. In
      general, behavioral economic indicators of reinforcing effectiveness did not
      differentiate bretazenil from a non-selective full agonist. These findings raise
      the possibility that degree of intrinsic efficacy of a benzodiazepine agonist may
      not be predictive of relative reinforcing effectiveness.

PMID- 20800978
TI  - Pythium insidiosum: an overview.
AB  - Pythium insidiosum is an oomycete pathogenic in mammals. The infection occurs
      mainly in tropical and subtropical areas, particularly in horses, dogs and
      humans. Infection is acquired through small wounds via contact with water that
      contains motile zoospores or other propagules (zoospores or hyphae). The disease,
      though described as emerging has in fact already been described since 1884.
      Depending on the site of entry, infection can lead to different forms of
      pythiosis i.e. a cutaneous, vascular, ocular, gastrointestinal and a systemic
      form, which is rarely seen. The infection is not contagious; no animal-animal or
      animal-human transmission has been reported so far. Therapy includes radical
      surgery, antifungal drugs, immunotherapy or a combination of these therapies. The
      prevention to contract the disease in endemic areas is difficult. Avoiding
      stagnant waters could be of help, although the presence of P. insidiosum on grass
      and soil in enzootic areas renders this practice useless.

PMID- 20800979
TI  - Identification of bovine papilloma virus 10 in teat warts of cattle by DNase
      SISPA.
AB  - Papilloma viruses are detected and identified by PCR with consensus primers
      designed from human papilloma virus sequences. These and other primers could not
      detect papilloma virus in bovine teat wart samples despite repeated attempts.
      DNase-SISPA, a metagenomic method for identifying viruses, could identify bovine
      papilloma virus type 10 in bovine teat warts. The sequence comparison between
      consensus primers and bovine papilloma virus type 10 sequences revealed many
      differences between consensus primers and BPV-10 sequences. We suggest, DNase
      SISPA may be used as an alternate method for papilloma virus diagnosis, in cases
      where PCR fails to identify papilloma viruses.

PMID- 20800980
TI  - Cell proliferation and survival mechanisms underlying the abnormal persistence of
      follicular cysts in bovines with cystic ovarian disease induced by ACTH.
AB  - Cystic ovarian disease (COD) is an important cause of infertility that affects
      cattle. Alterations in the ovarian micro-environment of females with follicular
      cysts could alter the normal processes of proliferation and programmed cell death
      in ovarian cells. Thus, the objective in the present study was to evaluate
      apoptosis and proliferation in induced ovarian cystic follicles in cows to
      investigate the follicular persistence. Stage of estrous cycle was synchronized
      in 10 heifers and 5 were then subjected to the induction of COD by administration
      of ACTH. After the ovariectomy number of in situ apoptotic cells by TUNEL assay,
      active caspase-3, FAS/FASLG and members of the BCL2 family were compared by
      immunohistochemistry and multiplex PCR and cell proliferation by evaluation of Ki
      67 protein and cyclin D1 and E mRNA. Significantly (p<0.05) lesser proliferative
      and apoptotic rates were found in cystic follicles from cows with COD compared
      with those with regular cycles. The relatively minimal proliferation found by
      immunohistochemistry with Ki-67 marker were confirmed by the gene expression of
      cyclin D1 and E. Lesser apoptotic rates were associated with decreased amounts of
      apoptotic-related proteins BAX, FASLG and caspase-3 as well as the in situ
      apoptosis detected by TUNEL assay, and increased amounts of the anti-apoptotic
      survival factor cellular BCL2 in the cystic follicles of the COD group. The
      BAX/BCL2 gene expression profile confirmed the immunohistochemical findings.
      Results from the present study indicate that cellular proliferation and apoptosis
      are altered in cystic follicles of cattle. The present study provides new
      insights into the molecular mechanisms underlying the aberrant persistence of
      follicular cysts and related diseases.

PMID- 20800982
TI  - Serial ultrasonographic observation of bilateral thalami in low birth weight
      infants with periventricular leukomalacia.
AB  - Periventricular leukomalacia is a major form of neuropathology in preterm infants
      that is associated with adverse motor and cognitive outcomes. The volume of
      periventricular white matter and corpus callosum has been reported to be
      diminished in infants with PVL, and the degree of the volume loss is correlated
      with the severity of neurological impairment. The thalamic index was calculated
      from the length, height, width of the thalamus, and thalamic volume was
      calculated using the formula for an ovoid in 62 low birth weight infants with
      gestational ages of 24-35weeks, 51 control infants (cerebral palsy, 1 case), and
      11 infants diagnosed with PVL (cerebral palsy, 7 cases) at postnatal days0-70.
      The indices of the right thalamus were lower in infants with PVL than in control
      infants from day0 to day70, and there were significant differences on days 21,
      28, 35, 42, 49, 56, 63, and 70. The indices of the left thalamus were lower in
      infants with PVL than in control infants from day0 to day70, and there were
      significant differences on days 21, 28, 35, 42, 49, 56, 63, and 70. The results
      of the present study suggest that the volume of the thalami is reduced and that
      thalamic injury is associated with white matter lesions in infants with PVL.

PMID- 20800981
TI  - Sleep quality and effects of position on sleep apnea in East Asian children.
AB  - OBJECTIVES: To assess whether obstructive sleep apnea syndrome (OSAS) affects
      sleep architecture and quality in East Asian children, and also to assess the
      effects of body position during sleep on respiratory disturbance during sleep.
      MATERIALS AND METHODS: We enrolled 50 consecutive East Asian children with
      habitual snoring between 2007 and 2009. Nineteen children had OSAS (apnea
      hypopnea index, AHI>=5; OSAS group) and 31 children were simple snorers (control
      group). They underwent polysomnography and physical examination of their nasal
      and oral cavities with a roentgenogram of the nasopharynx. Sleep architecture and
      other polysomnographic variables were compared between the OSAS and control
      groups. The effect of body position during sleep on respiratory disturbance was
      examined, and also in relation to obesity and adeno-tonsillar size. RESULTS:
      There was a decrease in total sleep time and in sleep efficiency, as well as
      increased arousal and heart rate (P<0.05) in the OSAS group. Sub-analysis of AHI
      according to sleep posture showed that AHI is higher when the patient is in the
      supine position than in the non-supine position (P=0.032). The presence of OSAS
      and kissing tonsils were contributing factors to the positional difference in AHI
      (P<0.05). Obesity and adenoid hypertrophy did not affect the positional
      difference of AHI. CONCLUSIONS: OSAS may have a greater influence on the sleep
      architecture of East Asian children, and East Asian children may have a higher
      AHI when sleeping in the supine position. Tonsillar hypertrophy and the presence
      of OSAS are possible contributing factors for positional difference of AHI in
      East Asian children.

PMID- 20800983
TI  - Differentiation between cavernous hemangiomas and untreated malignant neoplasms
      of the liver with free-breathing diffusion-weighted MR imaging: comparison with
      T2-weighted fast spin-echo MR imaging.
AB  - OBJECTIVE: To test interobserver variability of ADC measurements and compare the
      diagnostic performances of free-breathing diffusion-weighted (FBDW) with that of
      T2-weighted FSE (T2WFSE) MR imaging for differentiating between cavernous
      hemangiomas and untreated malignant hepatic neoplasms. MATERIALS AND METHODS:
      Thirty-five patients with cavernous hemangiomas and 35 with untreated hepatic
      malignant neoplasms had FBDW and T2WFSE MR imaging. Hepatic lesions were
      characterized with ADC measurement and visual evaluation. Interobserver agreement
      for ADC measurement was calculated. Association between ADC value and lesion type
      was assessed using univariate analysis. Sensitivity, specificity and accuracy of
      ADC values and visual evaluation of MR images for the diagnosis of untreated
      malignant hepatic neoplasm were compared. RESULTS: ADC measurements showed
      excellent interobserver correlation (intraclass correlation coefficient=0.980).
      Malignant neoplasms had lower ADC values than hemangiomas for the two observers
      (1.11*10(-3) mm2/s+/-.21*10(-3) vs. 1.77*10(-3) mm2/s+/-.29*10(-3) for observer 1
      and 1.11*10(-3) mm2/s+/-.19*10(-3) vs. 1.79*10(-3) mm2/s+/-.32*10(-3) for
      observer 2) and univariate analysis found significant correlations between lesion
      type and ADC values. Depending on ADC threshold value, accuracy for the diagnosis
      of malignant neoplasm varied from 82.9% to 94.3%. Using visual evaluation, FBDW
      showed better specificity and accuracy than T2WFSE MR images for the diagnosis of
      malignant neoplasm (97.1% vs. 77.1% and 94.3% vs. 62.9%, respectively).
      CONCLUSION: FBDW imaging provides reproducible quantitative information and
      surpasses the value of T2WFSE MR imaging for differentiating between cavernous
      hemangiomas and untreated malignant hepatic neoplasms.

PMID- 20800984
TI  - MR findings of focal eosinophilic liver disease using gadoxetic acid.
AB  - PURPOSE: The purpose of this study was to describe magnetic resonance (MR)
      findings of focal eosinophilic liver disease using gadoxetic acid (Gd-EOB-DTPA).
      MATERIALS AND METHODS: Nineteen patients (M:F=14:5; age range, 26-66 years; mean
      age, 50 years) with 35 focal eosinophilic liver lesions were included after
      reviewing the medical records of 482 patients who underwent Gd-EOB-DTPA-enhanced
      MR imaging (MRI) on a 3.0-T unit between April 2008 and June 2009. The diagnosis
      of focal eosinophilic liver disease was established by means of percutaneous
      liver biopsy or surgery and consistent clinical findings. Two radiologists
      retrospectively reviewed MR images with consensus. Margin, shape and distribution
      of the lesions were analyzed. We also evaluated signal intensity of focal hepatic
      lesions on T(1)- and T(2)-weighted images and patterns of enhancement in dynamic
      contrast study. RESULTS: The mean diameter of the lesions was 1.7 cm (range, 0.7
      6.1 cm). Most of the focal eosinophilic liver lesions [n=31/35 (88.6%)] had
      poorly defined margins. They were usually isointense or slightly hypointense
      [n=34/35 (97.2%)] on T(1)-weighted images and hyperintense [n=32/35 (91.4%)] on
      T(2)-weighted images. Dynamic study showed enhancement (rim or homogeneous) on
      the arterial phase [n=21/35 (60%)] and hypointensity on the late venous phase
      [n=31/35 (88.6%)]. All the lesions were hypointense on the hepatobiliary phase
      images. CONCLUSION: Focal eosinophilic liver lesions tend to be hyperintense on
      the arterial phase and hypointense on the late venous phase during dynamic study
      of Gd-EOB-DTPA-enhanced MRI. Although these findings mimic other focal hepatic
      lesions, poorly defined margins of the lesions and peripheral eosinophilia might
      help distinguish focal eosinophilic liver disease from other hepatic lesions.

PMID- 20800985
TI  - HPLC method validation for Digitalis and its analogue by pulsed amperometric
      detection.
AB  - We developed a highly sensitive and selective reversed-phase HPLC-pulsed
      amperometric detection (RP-HPLC-PAD) method for cardiac glycoside detection.
      Eight cardiac glycosides were completely separated within 45 min on a reversed
      phase column using a water-acetonitrile gradient, and were detected using a PAD
      under NaOH alkaline conditions. The detection (S/N=3) and quantification (S/N=10)
      limits for the cardiac glycosides were 0.1-0.3 and 0.3-0.8 ng, respectively. The
      linear regression coefficient was 0.9962-0.9998 for concentrations of 1-25
      MUg/mL. Cardiac glycosides in the Digitalis purpurea leaf displayed intra- and
      inter-day precisions (RSDs) of <9.30% and average recoveries of 98.63-99.94%. The
      contents of gitoxin, digitonin, and digitoxin in the D. purpurea were 0.197,
      0.11, and 0.379 mg/g for leaf dried at 60  degrees C, 0.058, 0.11, and 0.090 mg/g
      for leaf dried at ambient temperature, and N.D. (not detected), and 18.379 mg/g,
      N.D. for seed, respectively. We conclude that our method shows good precision and
      accuracy.

PMID- 20800986
TI  - Magnetic resonance imaging evaluation of the integration and maturation of
      semitendinosus-gracilis graft in anterior cruciate ligament reconstruction using
      autologous platelet concentrate.
AB  - PURPOSE: To evaluate integration and maturation of semitendinosus-gracilis (STG)
      grafts in anterior cruciate ligament (ACL) reconstruction with magnetic resonance
      imaging (MRI) in patients who underwent ACL reconstruction with STG with and
      without autologous platelet concentrate (APC). METHODS: A randomized single
      blinded evaluator prospective study was performed in 2 consecutive series of
      patients who underwent reconstruction over a 14-month period: 30 with APC use
      (group A) and 20 as control subjects (group B). At 6 months, an MRI evaluation
      was performed, with observation of the graft's maturation and presence or absence
      of synovial fluid at the tunnel-graft interface. To facilitate interpretation, a
      scoring scale was designed to evaluate graft integration and maturation. RESULTS:
      Regarding the presence of synovial fluid at the bone-graft interface, the test
      was negative in 86.84% of patients in group A and 94.74% in group B. A
      disorganized autograft signal pattern was found in 2.63% in group A and 5.26% in
      group B. Signal intensity was considered hypointense in 63.16% in group A and
      42.11% in group B, isointense in 34.21% in group A and 52.63% in group B, and
      hyperintense in 0% in both groups. The final mean score was 4.45 points in group
      A and 4.2 points in group B (P >= .05). Poor integration was found in 2.63% in
      group A and 5.26% in group B (P = .214). Good integration was found in 97.37% in
      group A and 94.74% in group B (P = .784). CONCLUSIONS: In our consecutive series
      of patients who underwent ACL reconstruction with STG grafts, 1 group with
      intraoperative APC use versus a control group, followed up by MRI at 6 months
      after reconstruction, we did not find any statistically significant benefit in
      the APC group in terms of integration assessment and graft maturation
      (ligamentization). LEVEL OF EVIDENCE: Level III, case-control study.

PMID- 20800987
TI  - Pre-emptive analgesia for chronic limb pain after amputation for peripheral
      vascular disease: a systematic review.
AB  - BACKGROUND: Chronic stump and phantom limb pain after amputation for critical
      ischemia significantly affect patients' quality of life and pose challenging
      clinical problems. Pre-emptive analgesia attempts to prevent chronic
      postoperative pain by minimizing painful stimuli before and during surgery.
      METHODS: This systematic literature review aimed to evaluate the evidence
      supporting the use of pre-emptive analgesia in minimizing the risk of chronic
      stump and phantom pain after lower limb amputation for critical ischemia of
      peripheral vascular disease. RESULTS: A total of 11 studies have been retrieved.
      Five different types of analgesic drugs were evaluated (local anesthetics,
      opiates, N-methyl-D-aspartate receptor antagonists, a(2)-agonist, and gamma
      aminobutyric acid analogues), administered separately or in combinations, through
      the oral, intravenous, epidural, or regional (perineural) route. The beneficial
      effect of combined bupivacaine, diamorphine, and clonidine in reducing the risk
      of phantom limb pain was supported by only one study (level 3 evidence). Epidural
      and perineural infusions containing local anesthetic +/- opiates are effective in
      treating acute perioperative pain, although not without potentially serious
      complications. Most studies were characterized by high drop-out rates because of
      disease-associated mortality. CONCLUSIONS: There is no robust evidence supporting
      the use of pre-emptive analgesia to minimize the risk of chronic pain after
      amputation for critical ischemia of peripheral vascular disease. The methods used
      are, however, effective in treating acute postoperative pain.

PMID- 20800988
TI  - Evaluation of two instruction methods to increase employment options for young
      adults with autism spectrum disorders.
AB  - We evaluated the efficacy of a vocational training program including behavioral
      skills training, and a "performance cue system" (i.e., a proprietary iPhone
      application adapted for the study) to teach targeted social-vocational skills to
      six young adults with an Autism Spectrum Disorder. In two separate studies,
      participants were employed to assist in the delivery of a fire safety education
      program. Participants were asked to wear an inflatable firefighter WalkAround(r)
      mascot costume and to perform 63 scripted behaviors in coordination with a fire
      prevention specialist who was the lead program presenter. In Study 1, three
      participants were initially exposed to established company training procedures
      comprised of behavioral skills training components to determine whether they met
      mastery of the skills. If necessary to reach criteria, participants were then
      exposed to a performance cue system. In Study 2, three additional participants
      were provided with the performance cue system alone, and then behavioral skills
      training if required. A single case, multiple-baseline design across subjects was
      used to evaluate efficacy of each intervention. Results indicate that 5 of 6
      participants reached criterion only after introduction of the cue system while
      the sixth reached criterion with behavioral skills training alone. The program
      received high satisfaction ratings from participants, their parents, and
      consumers. Implications and potential use of the PCS in other employment settings
      are discussed.

PMID- 20800989
TI  - An embodied account of serial order: how instabilities drive sequence generation.
AB  - Learning and generating serially ordered sequences of actions is a core component
      of cognition both in organisms and in artificial cognitive systems. When these
      systems are embodied and situated in partially unknown environments, specific
      constraints arise for any neural mechanism of sequence generation. In particular,
      sequential action must resist fluctuating sensory information and be capable of
      generating sequences in which the individual actions may vary unpredictably in
      duration. We provide a solution to this problem within the framework of Dynamic
      Field Theory by proposing an architecture in which dynamic neural networks create
      stable states at each stage of a sequence. These neural attractors are
      destabilized in a cascade of bifurcations triggered by a neural representation of
      a condition of satisfaction for each action. We implement the architecture on a
      robotic vehicle in a color search task, demonstrating both sequence learning and
      sequence generation on the basis of low-level sensory information.

PMID- 20800991
TI  - Covariate adjustment increases statistical power in randomized controlled trials.

PMID- 20800990
TI  - The origins of social impairments in autism spectrum disorder: studies of infants
      at risk.
AB  - Core impairments in social and communicative behaviors are among the defining
      characteristics of autism spectrum disorder (ASD), making this a model syndrome
      for investigating the mechanisms that underlie social cognition and behavior.
      Current research is exploring the origins of social impairments in prospective
      longitudinal studies of infants who are at high risk for ASD, defined as having
      an older sibling with the disorder. Behavioral studies that have followed these
      infants through to outcomes have found that during the early months of life they
      are no different from typically developing infants; they are socially interested,
      engaged and enjoy interactions with people. By the end of the first year risk
      signs for later ASD can be identified though no single marker has been
      identified. It seems that an aggregate of risk markers together may be needed to
      predict ASD. Other studies have compared infants at risk for ASD to low risk
      controls to identify neurocognitive endophenotypes. Several differences in subtle
      aspects of behavior and in brain organization have been found in infants younger
      than 12 months, though it is not known whether these differences are also risk
      markers for a later ASD diagnosis. The findings from these lines of research are
      used to provide a new view of ASD, as a disorder defined on the basis of
      alterations in the developmental trajectories across multiple domains. ASD is an
      emergent disorder that is characterized by the loss of social communication
      skills in the period between 9 and 24 months. Across children the rate, timing
      and severity of this loss is highly variable. Future research will lead to a
      greater understanding of the genetic and neurocognitive mechanisms that underlie
      these fundamental changes in the developmental patterns of individuals with ASD.

PMID- 20800992
TI  - Uptake of methods to deal with publication bias in systematic reviews has
      increased over time, but there is still much scope for improvement.
AB  - OBJECTIVE: To evaluate the measures taken to deal with publication bias across
      different categories of systematic reviews published in 2006 and to compare these
      with reviews published in 1996. STUDY DESIGN AND SETTING: PubMed was searched for
      systematic reviews published in 2006; 100 treatment effect, 50 diagnostic
      accuracy, 100 risk factor, and 50 gene-disease association reviews were randomly
      selected. RESULTS: The use of MEDLINE increased from 74% to 95%; checking
      references increased from 42% to 73%; use of Cochrane Library increased from 5%
      to 58%; and use of CINAHL increased from 8% in 1996 to 24% in treatment reviews,
      20% in diagnostic reviews, 18% in risk factor reviews, and 0% in genetic reviews
      published in 2006. A 20% increase was observed for explicit searching of non
      English-language studies in all reviews published in 2006. Efforts to search for
      unpublished studies increased to 61% from 35% in treatment reviews published in
      1996. Twenty-six percent of the reviews used funnel plots or related methods to
      test for publication bias compared with less than 6% in earlier reviews.
      CONCLUSION: Recent reviews show a significant improvement in the measures taken
      to prevent publication bias. However, few methods exist to deal with publication
      bias in the nonquantitative findings of systematic reviews.

PMID- 20800993
TI  - Validation testing of a three-component model of Short Form-36 scores.
AB  - OBJECTIVE: The two-component factor structure underlying Short Form-36 (SF-36)
      summary scores may not be valid worldwide. We studied a three-component model of
      SF-36 scores in Japan. STUDY DESIGN AND SETTING: The SF-36 scores came from
      representative samples of the population of Japan. Factor analysis and structural
      equation modeling were used. The two-component model gave physical component
      summary (PCS) scores and mental component summary (MCS) scores. The three
      component model gave scores on the PCS, the MCS, and also on the third component,
      which we call the role component summary (RCS) score. These were evaluated with
      external criteria. RESULTS: In the three-component model, the RCS was strongly
      associated with the role-physical, social functioning, and role-emotional
      subscales, whereas the PCS and MCS were associated with the physical functioning
      and mental health subscales, as expected. The goodness-of-fit index was 0.945 for
      the three-component model and 0.935 for the two-component model. The PCS
      discriminated between groups stratified by comorbid conditions, and the MCS
      discriminated between groups stratified by psychological depression. Absence from
      work was associated with both PCS and RCS. CONCLUSION: The three-component model
      is better than the two-component model, and it provides more useful PCS and MCS
      scores. Criteria for validation testing of the RCS are needed.

PMID- 20800994
TI  - Routine health insurance data for scientific research: potential and limitations
      of the Agis Health Database.
AB  - OBJECTIVE: Observational studies performed within routine health care databases
      have the advantage of their large size and, when the aim is to assess the effect
      of interventions, can offer a completion to randomized controlled trials with
      usually small samples from experimental situations. Institutional Health
      Insurance Databases (HIDs) are attractive for research because of their large
      size, their longitudinal perspective, and their practice-based information. As
      they are based on financial reimbursement, the information is generally reliable.
      STUDY DESIGN: The database of one of the major insurance companies in the
      Netherlands, the Agis Health Database (AHD), is described in detail. Whether the
      AHD data sets meet the specific requirements to conduct several types of clinical
      studies is discussed according to the classification of the four different types
      of clinical research; that is, diagnostic, etiologic, prognostic, and
      intervention research. The potential of the AHD for these various types of
      research is illustrated using examples of studies recently conducted in the AHD.
      CONCLUSION: HIDs such as the AHD offer large potential for several types of
      clinical research, in particular etiologic and intervention studies, but at
      present the lack of detailed clinical information is an important limitation.

PMID- 20800995
TI  - Fast density-based lesion detection in dermoscopy images.
AB  - Dermoscopy is one of the major imaging modalities used in the diagnosis of
      melanoma and other pigmented skin lesions. Automated assessment tools for
      dermoscopy images have become an important research field mainly because of inter
      and intra-observer variations in human interpretation. One of the most important
      steps in dermoscopy image analysis is automated detection of lesion borders. In
      this study, we introduce a border-driven density-based framework to identify skin
      lesion(s) in dermoscopy images. Unlike the conventional density-based clustering
      algorithms, proposed algorithm expands regions only at borders of a cluster that
      in turn speeds up the process without losing precision or recall. In our method,
      border regions are represented with one or more simple polygons at any time. We
      tested our algorithm on a dataset of 100 dermoscopy cases with multiple
      physicians' drawn ground truth borders. The results show that border error and f
      measure of assessment averages out at 6.9% and 0.86 respectively.

PMID- 20800996
TI  - Memory in frontal lobe epilepsy.
AB  - In contrast to the well studied long-term memory dysfunction of temporal lobe
      epilepsy (TLE) syndromes, data on memory performance of frontal lobe epilepsy
      (FLE) patients are limited and controversial. Behavioural and functional
      neuroimaging findings suggest that different regions within the frontal lobes
      contribute to long-term memory functioning, offering an explanation for the
      variability on memory function observed on patients with frontal lobe damage.
      Available evidence suggests memory dysfunction is a common finding on
      neuropsychological evaluation of FLE patients but prevalence and underlying
      mechanisms remain poorly understood. Variability on memory performance reported
      in FLE studies suggest this deficit may be dependant on the areas involved in
      seizure generation and spread. Recent research findings and the application of
      cognitive fMRI paradigms to FLE patients holds the promise of increasing
      understanding further.

PMID- 20800997
TI  - The relationship of brain weight to body mass index (BMI) upon autopsy in young
      people with severe mental illness.

PMID- 20800998
TI  - The relationships between schizophrenia symptom dimensions and executive
      functioning components.
AB  - Research investigating the relationships between executive functioning
      impairments and the positive, negative, and cognitive schizophrenia symptoms has
      produced inconsistent results. This inconsistency may be due to the tendency to
      view executive functioning as a unified process as opposed to multiple
      fractionated processes. A fractionated model of executive functioning has been
      supported in several studies of various populations, but few schizophrenia
      studies have used the factor analytic methods of these studies to empirically
      determine separate executive functioning components, causing conclusions
      regarding the relationships between these components and schizophrenia symptoms
      to be unreliable. The purposes of the present study were to (1) identify separate
      components of executive functioning by conducting a factor analysis of the
      performance of individuals with schizophrenia on the Delis Kaplan Executive
      Function System (D-KEFS) and (2) investigate the relationships between executive
      functioning components and the three schizophrenia symptom dimensions by
      correlating the derived factor scores with the scale scores of the Positive and
      Negative Symptom Scale (PANSS). An exploratory factor analysis revealed two
      separate components: inhibition/set shifting and mental flexibility. The results
      showed that the symptom dimensions were differentially related to impairments in
      executive functioning, with both negative and cognitive symptoms associated with
      the inhibition/set shifting component, cognitive symptoms alone associated with
      the mental flexibility component, and positive symptoms unrelated to either
      component.

PMID- 20800999
TI  - Alkhurma haemorrhagic fever--a viral haemorrhagic disease unique to the Arabian
      Peninsula.
AB  - The emergence and re-emergence of human and animal pathogens on a global scale
      continues unabated. One such pathogen is the arbovirus that causes Alkhurma
      haemorrhagic fever, which emerged in the Kingdom of Saudi Arabia in the mid
      1990s. It has since re-emerged in other regions of the country and threatens to
      widen its area of endemicity beyond the peninsula. Human and animal movements,
      especially those associated with the annual mass gathering event of Hajj
      (pilgrimage) may facilitate introduction into other continental masses, where it
      must be differentiated from dengue and other similar arboviral haemorrhagic
      fevers. In addition to dengue and Kadam viruses, which are known to be endemic in
      Saudi Arabia, it is thought that other flaviviruses exist in the region, though
      undetected. Collectively, these viruses present diagnostic challenges that may
      confound the recognition of clinical cases of Alkhurma haemorrhagic fever. The
      Saudi Ministry of Health is making concerted efforts to expand the evidence base
      in order to enhance the diagnostic and preventive protocols used to address the
      challenge of Alkhurma haemorrhagic fever.

PMID- 20801000
TI  - Leishmaniasis vaccines: past, present and future.
AB  - No vaccine exists against any form of leishmaniasis. Because recovery from
      infection is usually accompanied by a strong immunity and because it is possible
      to protect experimental animals against live challenge, hope for the development
      of a vaccine for humans has been high. However, leishmaniasis is a disease of the
      poor and the market for a vaccine is very limited. Until a few years ago, with
      minimal resources, only a pragmatic approach was possible for testing the first
      generation vaccines (i.e. killed whole parasites). Recently, funding has become
      available for developing defined second-generation vaccines, including
      recombinant proteins and DNA constructs. With new adjuvants also being developed
      there is new hope, and several new vaccines are in development against
      leishmaniasis.

PMID- 20801001
TI  - Update on SARS research and other possibly zoonotic coronaviruses.
AB  - The global outbreak of severe acute respiratory syndrome (SARS) in 2003 led to an
      intense and effective global response that stopped the spread of the disease by
      July 2003. There was also an intensive and very productive research effort to
      identify the aetiological agent, characterise the clinical and epidemiological
      features of the disease, understand the pathogenesis of the disease and the
      molecular biology of the virus, and design antiviral drugs and vaccines to treat
      and prevent the disease. In parallel with the SARS research effort there have
      been continuous improvements in our ability to detect and characterise other
      novel viruses. The SARS outbreak illustrates the importance of such detection
      tools in the response to public health threats. Studies since the SARS outbreak
      suggest that many novel viruses exist in animals and some, but probably not many,
      will present a risk to humans.

PMID- 20801002
TI  - Biosafety and biosecurity measures: management of biosafety level 3 facilities.
AB  - With the increasing biological threat from emerging infectious diseases and
      bioterrorism, it has become essential for governments around the globe to
      increase awareness and preparedness for identifying and containing those agents.
      This article introduces the basic concepts of laboratory management, laboratory
      biosafety and laboratory biosecurity. Assessment criteria for laboratories'
      biorisk should include both biosafety and biosecurity measures. The assessment
      requires setting specific goals and selecting management approaches. In order to
      implement technologies at the laboratory working level, a management team should
      be created whose role is to implement biorisk policies, rules and regulations
      appropriate for that facility. Rules and regulations required by government
      authorities are presented, with special emphasis on methods for air control, and
      liquid and solid waste management. Management and biorisk measures and
      appropriate physical facilities must keep pace, ensuring efficient facilities
      that protect workers, the environment, the product (research, diagnostic and/or
      vaccine) and the biological pathogen.

PMID- 20801003
TI  - Rabies and African bat lyssavirus encephalitis and its prevention.
AB  - Unlike any other human infection, encephalitis caused by dog rabies virus is
      always fatal. Rabies and other lyssaviruses have been found in unexpected places,
      and human disease, especially paralytic rabies, has gone unrecognised. Evidence
      is emerging that rabies-related bat lyssaviruses are enzootic across Europe,
      Africa, Asia and Australia, but none has been detected in the Americas. The
      epidemiology and origins of African lyssaviruses are discussed. Ideal rabies
      prophylaxis (pre-exposure immunisation followed by post-exposure booster
      vaccination) has proved 100% effective; hence all human deaths result from
      failure of prevention. Rabies vaccines of known quality are unaffordable for the
      majority in Africa. Although intradermal regimens requiring <40% of the usual
      vaccine dose are economical and are recommended by the World Health Organization,
      several problems have inhibited their use. A new, simplified, economical post
      exposure vaccine regimen that uses an initial dose of intradermal injections at
      four sites overcomes many of the difficulties of the previous methods: it is at
      least as immunogenic as the standard intramuscular course of tissue-culture
      vaccine; is safer in inexperienced hands; requires fewer than two ampoules of
      vaccine and only three instead of five clinic visits. Recent data should increase
      the confidence of physicians to use the World Health Organization-accredited
      rabies vaccines more efficiently and at lower cost.

PMID- 20801004
TI  - Preparation of silver nanoparticles using tryptophan and its formation mechanism.
AB  - A non-toxic route was used for the preparation of silver nanoparticles using
      tryptophan (Trp) as reducing/stabilizing agent in the presence of cetyltrimethyl
      ammonium bromide (CTAB). Role of water soluble neutral polymer
      poly(vinylpyrrolidone) (PVP) has been studied on the growth of yellow colour
      silver nanoparticle formation. The synthesized nanostructures were characterized
      by UV-Visible absorption spectroscopy, transmission electron microscopy (TEM) by
      observing the size and distribution of silver nanoparticles. As the reaction
      proceeded, particles grew up to about 10 and 20 nm in the presence and absence of
      PVP, respectively, as determined by TEM. The formed nanoparticles showed the
      highest absorption plasmon band at 425 nm. Rate of silver sol formation increases
      with the [Trp], [CTAB] and [PVP], reaching a limiting value and then decreases
      with the increase in concentrations of these reagents. It was observed that
      nanoparticles are spherical, aggregated and poly dispersed in the absence and
      presence of PVP, respectively. On the basis of kinetic data, a suitable mechanism
      is proposed and discussed for the silver sol formation.

PMID- 20801005
TI  - Polystyrene microspheres based sandwich immunosensor using CdTe nanoparticles
      amplification and ultrasensitive flow-injection chemiluminescence detection.
AB  - In this paper we propose a specific sandwich immunoassay method for human
      immunoglobulin G (HIgG). This immunoassay protocol takes advantage of sandwich
      binding of primary and secondary antibodies for increased specificity.
      Polystyrene microspheres (PS) serve as immobilizing support, site for sandwich
      immunoassay and then subsequently used for chemiluminescence (CL) detections. In
      this sandwich immunoassay, PS microspheres were modified with the primary anti
      HIgG (Ab1) via electrostatic interaction, while CdTe nanoparticles (CdTeNPs) were
      modified with horseradish peroxidase labeled anti-HIgG (Ab2) via covalent
      binding. Antigen HIgG (Ag) was specifically captured by the first and secondary
      antibody and form sandwich immunoassay format. Combination of the remarkable
      sensitivity of CL method and the use of CdTe NPs as anti-HIgG-HRP carrier for the
      enzymatic signal amplification, provide a linear response range of HIgG from 0.01
      to 300 ng mL(-1) with an extremely low detection limit of 0.3 pg mL(-1). This
      immunoassay system has many desirable merits including sensitivity, accuracy, and
      little required instrumentation. The assay results were compared with enzyme
      linked immunosorbent assay (ELISA), and showed relatively good reliability.
      Significantly the new protocol may become quite promising technique for protein
      immune-detection as well as DNA analysis and other biological analyses.

PMID- 20801006
TI  - [Neonatal resuscitation and unreasonable obstinacy: a hospital ordered to pay
      damages].

PMID- 20801007
TI  - [A case of extravaginal twisting of spermatic cord].
AB  - Extravaginal twisting of the spermatic cord is rare and its management is still
      open to debate. We report the case in a 12-day-old boy with right testicular pain
      evolving since birth. Scrototomy revealed a complete twist of the extravaginal
      spermatic cord. The testis was already necrotic and the intervention consisted in
      orchidectomy and orchidopexy. Twisting of the extravaginal cord remains a
      surgical emergency, which allows contralateral orchydopexy.

PMID- 20801008
TI  - Physiological characteristics of several rumen protozoa grown in vitro with
      observations on within and among species variation.
AB  - When fed equal amounts of substrate, two Epidinium caudatum clone cultures of
      markedly different size produced similar volumes of microbial protoplasm.
      Addition of up to 50% volume of 72h culture medium had no inhibitory effects on
      growth of Epidinium. Two clone cultures of Epidinium caudatum from Australia had
      longer generation times and showed less substrate attachment when compared to
      Ohio clones of this same species. Substitution of alfalfa for orchardgrass in the
      normal substrate increased Epidinium concentrations, while feeding only ground
      orchardgrass or alfalfa resulted in a marked decrease or disappearance of the
      protozoa. Eudiplodinium impalae, isolated from rumen contents of a steer in
      Australia, was successfully cultured, with generation times for this species
      averaging 11.3h. Reducing particle size of the substrates by ball-milling was
      detrimental for growth of Entodinium and Epidinium; however, Eudiplodinium
      increased in concentration. Significant concentration differences were observed
      among six clone cultures of Epidinium obtained from Europe. A generation time of
      18.7h was measured for Enoploplastron triloricatum when the culture was
      transferred every 12h. Lowering the incubation temperature to 34 degrees C
      completely inhibited protozoal growth of Epidinium and Entodinium exiguum after
      12 days, but not for Entodinium caudatum.

PMID- 20801009
TI  - Bone marrow stromal cells as an inducer for cardiomyocyte differentiation from
      mouse embryonic stem cells.
AB  - Bone marrow stromal cells (BMSCs) secrete soluble factors and display varied cell
      biological functions. To confirm the ability and efficiency of BMSCs to induce
      embryonic stem cells (ESCs) into cardiomyocytes, mouse embryoid bodies (EBs) were
      co-cultured with rat BMSCs. After about 10 days, areas of rhythmically
      contracting cells in more solid aggregates became evident with bundle-like
      structures formed along borders between EB outgrowth and BMSC layer. ESC-derived
      cardiomyocytes exhibited sarcomeric striations when stained with troponin I (Trop
      I), organized in separated bundles. Besides, the staining for connexin 43 was
      detected in cell-cell junctions, which demonstrated that ESC-derived
      cardiomyocytes were coupled by gap junction in culture. The related genes of
      cardiomyocytes were found in these beating and no-beating EBs co-cultured with
      BMSCs. In addition, an improved efficiency of cardiomyocyte differentiation from
      ESC-BMSC co-culture was found in the serum-free medium: 5-fold up-regulation in
      the number of beating area compared with the serum medium. Effective cardiac
      differentiation was also recognized in transfer filter assay and in condition
      medium obtained from BMSC culture. A clear increase in the expression of cardiac
      genes and TropI protein confirmed further cardiac differentiation by BMP4 and
      Retinoic Acid (RA) treatment. These results demonstrate that BMSCs can induce
      cardiomyocyte differentiation from ESCs through soluble factors and enhance it
      with BMP4 or RA treatment. Serum-free ESC-BMSC co-culture represents a defined in
      vitro model for identifying the cardiomyocyte-inducing activity from BMSCs and,
      in addition, a straightforward experimental system for assessing clinical
      applications.

PMID- 20801010
TI  - Omalizumab-induced decrease of FcxiRI expression in patients with severe allergic
      asthma.
AB  - BACKGROUND: It is documented that omalizumab treatment reduces the cell surface
      expression of immunoglobulin E high-affinity receptor (FcERI) on several cell
      types. This has not been investigated in patients with uncontrolled severe
      persistent allergic asthma. METHODS: In a double-blind, randomized, placebo
      controlled study, patients with severe allergic asthma uncontrolled by high dose
      inhaled corticosteroids and long-acting beta(2)-agonist received either
      omalizumab (n = 20) or placebo (n = 11) over 16 weeks at appropriate doses and
      frequencies. Baseline and end of study (week 16) FcERI expression on basophils
      and plasmacytoid dendritic cells was determined by flow cytometry for the primary
      endpoint. Secondary efficacy endpoints included asthma control and lung function
      as part of an initial investigation into the use of FcERI expression as a marker
      of response. RESULTS: In the omalizumab group, and with respect to placebo, FcERI
      expression was significantly reduced at end of study on basophils (-82.6%, p <
      0.01) and plasmacytoid dendritic cells (-44.2%, p = 0.029). FcERI expression
      reduction was not found to be correlated with clinical response. CONCLUSIONS:
      Long-term omalizumab treatment induced reduction of FcERI expression on
      circulating basophils and plasmacytoid dendritic cells. These changes were not
      associated with those of clinical features related to severe asthma, which does
      not support further investigation into its use as a predictive marker of
      response. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov
      (identifier: NCT00454051) and the European Clinical Trials Database, EudraCT
      (identifier: 2006-003591-35).

PMID- 20801011
TI  - Apoptosis: embedded in membranes.
AB  - Many different signals for cell death converge on outer mitochondrial membrane
      permeabilization, a process controlled by the Bcl-2 family of proteins. Recent
      structural and biochemical analyses emphasize that key regulatory interactions
      between different classes of Bcl-2 family members occur at and in intracellular
      membranes, and insertion into membranes causes functionally important
      conformational changes in the proteins.

PMID- 20801013
TI  - A gold-sputtered carbon paper as an anode for improved electricity generation
      from a microbial fuel cell inoculated with Shewanella oneidensis MR-1.
AB  - Gold is among the highly conductive and stable materials, which are ideal anodes
      for microbial fuel cells (MFCs). However, previous studies have shown that bare
      gold surface is recalcitrant for the colonization of some exoelectrogens, e.g.,
      Shewanella putrefacians. In this work, the problem regarding the poor bio
      compatibility of gold as an anode material was sorted out through coupling it
      with carbon paper. A new composite anode material was fabricated through
      sputtering gold layer homogeneously on carbon paper matrix. Results of cyclic
      voltammetry and electrochemical impedance spectroscopy in Fe(CN)6(3-/4-) solution
      demonstrated better electrochemical performance of the carbon paper-gold (C-Au)
      composite than either carbon paper or bare gold, when they were used in MFCs.
      With Shewanella oneidensis MR-1 as the inoculum, the C-Au anode-based MFC
      produced total electric charges higher than the carbon-paper-anode-based MFC by
      47%. The cyclic voltammetry analysis and the scanning electron microscopy
      observation showed that the MR-1 biofilm growth was accelerated when the carbon
      paper surface was sputtered with gold. Utilization of such a carbon paper-gold
      composite significantly enhanced the MFC performance.

PMID- 20801014
TI  - Comparison of prostate IMRT and VMAT biologically optimised treatment plans.
AB  - Recently, a new radiotherapy delivery technique has become clinically available-
      volumetric modulated arc therapy (VMAT). VMAT is the delivery of IMRT while the
      gantry is in motion using dynamic leaf motion. The perceived benefit of VMAT over
      IMRT is a reduction in delivery time. In this study, VMAT was compared directly
      with IMRT for a series of prostate cases. For 10 patients, a biologically
      optimized seven-field IMRT plan was compared with a biologically optimized VMAT
      plan using the same planning objectives. The Pinnacle RTPS was used. The
      resultant target and organ-at-risk dose-volume histograms (DVHs) were compared.
      The normal tissue complication probability (NTCP) for the IMRT and VMAT plans was
      calculated for 3 model parameter sets. The delivery efficiency and time for the
      IMRT and VMAT plans was compared. The VMAT plans resulted in a statistically
      significant reduction in the rectal V25Gy parameter of 8.2% on average over the
      IMRT plans. For one of the NTCP parameter sets, the VMAT plans had a
      statistically significant lower rectal NTCP. These reductions in rectal dose were
      achieved using 18.6% fewer monitor units and a delivery time reduction of up to
      69%. VMAT plans resulted in reductions in rectal doses for all 10 patients in the
      study. This was achieved with significant reductions in delivery time and monitor
      units. Given the target coverage was equivalent, the VMAT plans were superior.

PMID- 20801015
TI  - Interleukin-1beta regulates the migratory potential of MDAMB231 breast cancer
      cells through the hypoxia-inducible factor-1alpha.
AB  - The casual relationship between inflammation and tumour progression has been
      widely accepted and the etiology of breast cancer has been associated with
      inflammatory processes. Interleukin (IL)-1beta, besides its central role in
      inflammation, has also been recognised as a powerful player in tumour
      progression, angiogenesis and invasiveness. Recently, there has been considerable
      interest in understanding the non-hypoxic upregulation of the hypoxia-inducible
      factor (HIF)-1alpha by IL-1 in neoplastic cells since aberrant expression of HIF
      1alpha correlates with tumour progression. Here, using the highly invasive human
      breast cancer cell line MDAMB231, we studied the effect of IL-1beta on tumour
      cell migration along with HIF-1alpha accumulation. We observed that non-hypoxic
      induction of HIF-1alpha by IL-1beta in MDAMB231 was associated with increased
      cell migration, paralleled by upregulation of p38 MAPK phosphorylation and
      CXCL8/CXCR1 expression. Inhibition of HIF-1alpha by siRNA resulted in a
      significant reduction of CXCR1 expression and IL-1beta-induced cell migration in
      MDAMB231 cells, thus confirming a role of HIF-1alpha in the non-hypoxic-IL-1beta
      dependent induction of migratory potentials. Our observation that IL-1 induces
      HIF-1alpha accumulation in MDAMB231 cells was confirmed in tumour cells growing
      in vivo using an experimental approach, mimicking the endogenous release of IL-1
      in mice bearing MDAMB231 xenografts. Our in vivo data, along with the fact that
      inhibition of HIF-1alpha resulted in the decrease of IL-1beta-promoted cell
      migration, further support the link between inflammation and cancer. The overall
      results may have important implications in those therapeutic approaches aimed to
      inhibit IL-1-mediated activities in tumour cells, specifically in breast cancer.

PMID- 20801016
TI  - Early cessation of the clinical development of LiPlaCis, a liposomal cisplatin
      formulation.
AB  - PURPOSE: To evaluate the safety and tolerability of LiPlaCis, a liposomal
      formulated platinum compound, in patients with solid tumours and to determine the
      maximum tolerated dose (MTD) of intravenous (i.v.) LiPlaCis. and to assess plasma
      and urine pharmacokinetics and plasma biomarkers. PATIENTS AND METHODS: Patients
      with solid tumours without standard therapeutic options were enrolled to receive
      LiPlaCis administered as a 1 h infusion without additional hydration every 3weeks
      until RECIST progression or unacceptable toxicity. Cohorts of 3-6 patients were
      treated at each dose level until MTD was reached. RESULTS: Eighteen patients were
      enrolled and 64 cycles were delivered. At the first dose level 3 patients
      experienced an infusion reaction. Despite prophylactic pre-medication and
      prolongation of the infusion to 2 h in further patients, three other patients had
      mild acute infusion reactions. Toxicity at the fifth dose level of 120 mg
      consisted of grade 2 renal toxicity reversible after hydration in 2 patients and
      grade 4 thrombocytopaenia in one of these patients. Peak plasma concentrations
      and AUC were dose proportional. The interpatient variability in the clearance of
      total LiPlaCis-derived platinum was 41%. Platinum was excreted via the urine
      mainly during the first 24 h after administration. Investigated plasma biomarkers
      sPLA(2) and SC5b-9 were related to, but not predictive for, acute infusion
      reactions. CONCLUSION: The observed safety profile suggests no benefit over
      standard cisplatin formulations and LiPlaCis will require reformulation to enable
      further development.

PMID- 20801017
TI  - Influence of vegetable oils fatty acid composition on reaction temperature and
      glycerides conversion to biodiesel during transesterification.
AB  - Presence of unreacted glycerides in biodiesel may reduce drastically its quality.
      This is why conversion of raw material in biodiesel through transesterification
      needs to readjust reaction parameter values to complete. In the present work,
      monitoring of glycerides transformation in biodiesel during the
      transesterification of vegetable oils was carried out. To check the influence of
      the chemical composition on glycerides conversion, selected vegetable oils
      covered a wide range of fatty acid composition. Reactions were carried out under
      alkali-transesterification in the presence of methanol. In addition, a multiple
      regression model was proposed. Results showed that kinetics depends on chemical
      and physical properties of the oils. It was found that the optimal reaction
      temperature depends on both length and unsaturation degree of vegetable oils
      fatty acid chains. Vegetable oils with higher degree of unsaturation exhibit
      faster monoglycerides conversion to biodiesel. It can be concluded that fatty
      acid composition influences reaction parameters and glycerides conversion, hence
      biodiesel yield and economic viability.

PMID- 20801018
TI  - Concepts and profitability of biogas production from landscape management grass.
AB  - Landscape management grass is generally harvested late, resulting in unfavorable
      composition for many utilization purposes. This study explores various technical
      concepts of biogas production and their economic viability. The Lower Oder Valley
      National Park is taken here as an example. This National Park in North-East
      Germany comprises large grassland areas with conservation-related restrictions on
      management. The concepts of biogas production and use considered are: (1)
      decentralized digestion and use of biogas at five autonomous combined heat and
      power (CHP) units, (2) decentralized digestion and delivery of the biogas to a
      centralized CHP unit, (3) decentralized digestion, upgrading of the biogas and
      feeding into the natural gas grid, and (4) one central biogas plant with
      centralized CHP unit. Annual costs and revenues of biogas production were
      calculated for each alternative. Biogas production from landscape management
      grass meets the conservational demands of late cutting periods and under certain
      circumstances shows a profit.

PMID- 20801019
TI  - The slow and fast pyrolysis of cherry seed.
AB  - The slow and fast pyrolysis of cherry seeds (CWS) and cherry seeds shells (CSS)
      was studied in fixed-bed and fluidized bed reactors at different pyrolysis
      temperatures. The effects of reactor type and temperature on the yields and
      composition of products were investigated. In the case of fast pyrolysis, the
      maximum bio-oil yield was found to be about 44 wt% at pyrolysis temperature of
      500  degrees C for both CWS and CSS, whereas the bio yields were of 21 and 15 wt%
      obtained at 500  degrees C from slow pyrolysis of CWS and CSS, respectively. Both
      temperature and reactor type affected the composition of bio-oils. The results
      showed that bio-oils obtained from slow pyrolysis of CWS and CSS can be used as a
      fuel for combustion systems in industry and the bio-oil produced from fast
      pyrolysis can be evaluated as a chemical feedstock.

PMID- 20801020
TI  - Trypsin-enabled construction of anti-fouling and self-cleaning polyethersulfone
      membrane.
AB  - Constructing anti-fouling and self-cleaning membrane surfaces based on covalent
      attachment of trypsin on poly(methacrylic acid)-graft-polyethersulfone (PMAA-g
      PES) membrane was reported. The carboxylic acid groups enriched on asymmetric
      PMAA-g-PES membrane surface were activated with 1-ethyl-(3-3-dimethylaminopropyl)
      carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS) and employed as
      chemical anchors for the conjugation with amino groups of trypsin. Activity
      assays showed that such chemically immobilized trypsin was much more active and
      stable than that of the physically adsorbed counterpart. Trypsin covalently
      attached on membrane surface could substantially resist protein fouling in
      dynamic flow process. The considerable enhancement of protein solution permeation
      flux was observed as a consequence of rapid enzymatic degradation of protein
      deposited onto membrane surface. The permeation flux of the membrane could be
      recovered upon simple hydraulic flush after protein filtration, suggesting
      superior self-cleaning property. After multi-cycle BSA filtration over 15-day
      period, the active self-cleaning membrane maintained more than 95.0% of its
      initial flux.

PMID- 20801021
TI  - Absorptive removal of biomass tar using water and oily materials.
AB  - Water is the most common choice of absorption medium selected in many
      gasification systems. Because of poor solubility of tar in water, hydrophobic
      absorbents (diesel fuel, biodiesel fuel, vegetable oil, and engine oil) were
      studied on their absorption efficiency of biomass tar and compared with water.
      The results showed that only 31.8% of gravimetric tar was removed by the water
      scrubber, whereas the highest removal of gravimetric tar was obtained by a
      vegetable oil scrubber with a removal efficiency of 60.4%. When focusing on light
      PAH tar removal, the absorption efficiency can be ranked in the following order;
      diesel fuel>vegetable oil>biodiesel fuel>engine oil>water. On the other hand, an
      increase in gravimetric tar was observed for diesel fuel and biodiesel fuel
      scrubbers because of their easy evaporation. Therefore, the vegetable oil is
      recommended as the best absorbent to be used in gasification systems.

PMID- 20801022
TI  - Pathogen removal in farm-scale psychrophilic anaerobic digesters processing swine
      manure.
AB  - This study assessed the efficiency of commercial-scale psychrophilic anaerobic
      digestion in sequencing batch reactors (PADSBRs) for pathogen removal from pig
      manure. The impact of treatment cycle length and of hydraulic flow regimes on
      pathogen removal efficiency was investigated. Two conventionally operated SBRs
      (BR1 and BR2) and two SBRs simultaneously fed during the draw step (BR3 and BR4)
      were monitored over a two-year period. PADSBRs significantly decreased the
      concentration of coliforms, Salmonella, Campylobacter spp., and Y.
      enterocolitica, respectively from about 10(6), 10(3) CFU g(-1), 10(3), and 10(4)
      CFU g(-1) to undetectable levels in most samples. Densities of the gram-positive
      Clostridium perfringens and Enterococcus spp. remained high (10(5) CFU g(-1)) in
      the digesters throughout treatment. The PADSBRs maintained the same level of
      pathogen removal when the treatment cycle length was reduced from 2 to 1 week.
      Mass balances on volatile fatty acids (VFAs) revealed short-circuits of inlet
      flow respectively averaging 6.3% and 6.4% for BR3 and BR4, significantly reducing
      the overall performance of these reactors regarding pathogens removal. The
      results obtained in this study show the ability of low temperature anaerobic
      digestion to remove or significantly reduce indicator and pathogen concentration
      from raw pig manure.

PMID- 20801023
TI  - Impact of torrefaction on the grindability and fuel characteristics of forest
      biomass.
AB  - Thermal pretreatment or torrefaction of biomass under anoxic condition can
      produce an energy dense and consistent quality solid biomass fuel for combustion
      and co-firing applications. This paper investigates the fuel characteristics and
      grindability of pine chips and logging residues torrefied at temperatures ranging
      from 225  degrees C to 300  degrees C and 30 min residence time. Grinding
      performance of torrefied biomass evaluated by determining energy required for
      grinding, particle size distribution and average particle size were compared with
      raw biomass and coal. Specific energy required for grinding of torrefied biomass
      decreased significantly with increase in torrefaction temperatures. The grinding
      energy of torrefied biomass was reduced to as low as 24 kW h/t at 300  degrees C
      torrefaction temperature. The gross calorific value of torrefied chips increased
      with increase in torrefaction temperature. Torrefaction of biomass clearly showed
      the improved fuel characteristics and grinding properties closer to coal.

PMID- 20801024
TI  - Immobilized humic substances on an anion exchange resin and their role on the
      redox biotransformation of contaminants.
AB  - A novel technique to immobilize humic substances (HS) on an anion exchange resin
      is presented. Immobilized HS were demonstrated as an effective solid-phase redox
      mediator (RM) during the reductive biotransformation of carbon tetrachloride (CT)
      and the azo model compound, Reactive Red 2 (RR2). Immobilized HS increased ~4
      fold the extent of CT reduction to chloroform by a humus-reducing consortium in
      comparison to incubations lacking HS. Immobilized HS also increased 2-fold the
      second-order rate constant of decolorization of RR2 as compared with sludge
      incubations lacking HS. To our knowledge, the present study constitutes the first
      demonstration of immobilized HS serving as an effective solid-phase RM during the
      reductive biotransformation of priority contaminants. The immobilizing technique
      developed could be appropriate for enhancing the redox biotransformation of
      recalcitrant pollutants in anaerobic wastewater treatment systems.

PMID- 20801025
TI  - WITHDRAWN: A continuous transesterification process of Jatropha curcas oil in the
      presence of biodiesel as a green solvent.
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- 20801026
TI  - Identification of amino acid residues responsible for increased thermostability
      of feruloyl esterase A from Aspergillus niger using the PoPMuSiC algorithm.
AB  - Feruloyl esterases are key enzymes involved in the complete hydrolysis of
      hemicellulose. In order to improve the thermostability of feruloyl esterase A
      (FaeA) from Aspergillus niger CIB 423.1, the PoPMuSiC algorithm was applied to
      predict the folding free energy change (DeltaDeltaG) of amino acid substitutions.
      Four amino acid substitutions (S92A, D93G, D174A and S187F) were introduced into
      the enzyme by site-directed mutagenesis and the enzymes were produced in Pichia
      pastoris KM71. No obvious changes in thermal stability resulted from
      substitutions S92A and D174A, but, compared to the wild-type enzyme which has a
      half-life of inactivation of 8 min, the half-lives of enzymes with a D93G or
      S187F substitution increased to 9.4 and 60.5 min, respectively. The double mutant
      D93G/S187F displayed a synergistic effect with a t1/2 value of 77.0 min. It also
      displayed over 10-fold increase in catalytic turnover frequency. The result will
      benefit further investigation of the thermostability of feruloyl esterase A.

PMID- 20801027
TI  - An artificial intelligence approach to Bacillus amyloliquefaciens CCMI 1051
      cultures: application to the production of anti-fungal compounds.
AB  - The combined effect of incubation time (IT) and aspartic acid concentration (AA)
      on the predicted biomass concentration (BC), Bacillus sporulation (BS) and anti
      fungal activity of compounds (AFA) produced by Bacillus amyloliquefaciens CCMI
      1051, was studied using Artificial Neural Networks (ANNs). The values predicted
      by ANN were in good agreement with experimental results, and were better than
      those obtained when using Response Surface Methodology. The database used to
      train and validate ANNs contains experimental data of B. amyloliquefaciens
      cultures (AFA, BS and BC) with different incubation times (1-9 days) using
      aspartic acid (3-42 mM) as nitrogen source. After the training and validation
      stages, the 2-7-6-3 neural network results showed that maximum AFA can be
      achieved with 19.5 mM AA on day 9; however, maximum AFA can also be obtained with
      an incubation time as short as 6 days with 36.6 mM AA. Furthermore, the model
      results showed two distinct behaviors for AFA, depending on IT.

PMID- 20801029
TI  - Affibody-displaying bionanocapsules for specific drug delivery to HER2-expressing
      cancer cells.
AB  - A novel HER2-targeted carrier was developed using bionanocapsules (BNCs).
      Bionanocapsules (BNCs) are 100-nm hollow nanoparticles composed of the L-protein
      of hepatitis B virus surface antigen. An affibody of HER2 was genetically
      displayed on the BNC surface (Z(HER2)-BNC). For the investigation of binding
      affinity, Z(HER2)-BNC was incubated with the cancer cell lines SK-BR-3 (HER2
      positive), and MDA-MB-231 (HER2 negative). For analysis of HER2 targeting
      specificity, Z(HER2)-BNC or Z(WT)-BNC (without affibody) was incubated with both
      SK-BR-3 and MDA-MB-231 cells by time lapse and concentration. For the delivery of
      encapsulated molecules (calcein), fluorescence of Z(HER2)-BNC mixed with
      liposomes was also compared with that of Z(WT)-BNC and nude liposomes by
      incubation with SK-BR-3 cells. As a result, Z(HER2)-BNC-liposome complex
      demonstrated the delivery to HER2-expressing cells (SK-BR-3) with a high degree
      of specificity. This indicates that genetically engineered BNCs are promising
      carrier for cancer treatment.

PMID- 20801028
TI  - Synthesis and evaluation of 1,2,4-triazolo[1,5-c]pyrimidine derivatives as A2A
      receptor-selective antagonists.
AB  - Movement disorders such as Parkinson's disease and Huntington's disease are
      serious life-limiting and debilitating movement disorders. Their onset typically
      occurs from mid-life to late in life, and effective diagnostic techniques for
      detecting and following the disease course are lacking. Our goal is to develop
      receptor imaging agents for positron emission tomography (PET) that selectively
      target the most relevant subtype of adenosine receptors (AR) that are highly
      expressed in the striatum, that is, the A(2A) AR. To further this goal, we have
      synthesized and characterized pharmacologically a family of high affinity A(2A)
      AR ligands, based on the known antagonist, SCH 442416 (R=-Me), which have
      structural variability on the terminus (R=-Et, -i-Pr, -allyl, and others). A O
      fluoroethyl analogue suitable for use as a PET tracer had a K(i) value of 12.4 nM
      and was highly selective for the A(2A) AR in comparison to the A(1) and A(3) ARs.

PMID- 20801030
TI  - Discovery of potent and selective histamine H3 receptor inverse agonists based on
      the 3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one scaffold.
AB  - A novel series of potent histamine H(3) receptor inverse agonists based on the
      3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one scaffold has been discovered. Several
      compounds display high selectivity over other histamine receptor subtypes and
      have favorable physicochemical properties, low potential for CYP450 enzyme
      inhibition and high metabolic stability in microsomal preparations. (R)-2
      Cyclopropylmethyl-8-(1-isopropyl-piperidin-4-yloxy)-3-methyl-3,4-dihydro-2H
      pyrazino[1,2-a]indol-1-one (8t) showed good in vivo efficacy after per os
      application in an acute rat dipsogenia model of water intake.

PMID- 20801031
TI  - Preparation and characterization of novel 4-bromo-3,4-dimethyl-1-phenyl-2
      phospholene 1-oxide and the analogous phosphorus heterocycles or phospha sugars.
AB  - 4-Bromo-3,4-dimethyl-1-phenyl-2-phospholene 1-oxide (3c) was first synthesized
      from 3,4-dimethyl-1-phenyl-2-phospholene 1-oxide (2c) by a bromo-radical
      substitution reaction occurred at C-4 position by N-bromosuccinimide and 2,2'
      azobisisobutyronitrile. The novel phospha sugar analogue 3c exerted high anti
      proliferative effect on U937 cells evaluated by MTT in vitro methods and was much
      more efficient than that of Gleevec, which is known as a molecule targeting
      chemotherapeutical agent. The substitution of 2-phospholenes at C-3 and C-4
      position with methyl groups as well as 4-bromo substituent suggests a good anti
      proliferative effect.

PMID- 20801032
TI  - Novel bisphosphonate inhibitors of the human farnesyl pyrophosphate synthase.
AB  - A structure-based approach was pursued in designing novel bisphosphonate
      inhibitors of the human farnesyl pyrophosphate synthase (hFPPS). Preliminary SAR
      and structural evidence for the simultaneous binding of these inhibitors into the
      isopentenyl pyrophosphate (IPP) and the geranyl pyrophosphate (GPP) substrate sub
      pockets of the enzyme are presented.

PMID- 20801033
TI  - Probing the active-site requirements of human intestinal N-terminal maltase
      glucoamylase: the effect of replacing the sulfate moiety by a methyl ether in
      ponkoranol, a naturally occurring alpha-glucosidase inhibitor.
AB  - Ponkoranol is a naturally occurring glucosidase inhibitor isolated from the plant
      Salacia reticulata. The compound comprises a sulfonium ion with an internal
      sulfate counter ion. We report here an efficient synthetic route to 3'-O-methyl
      ponkoranol to test the hypothesis that occupation of a hydrophobic pocket by a
      methyl group instead of the polar sulfate ion within the active site of human N
      terminal maltase glucoamylase would be beneficial. The synthetic strategy relies
      on the nucleophilic attack of 2,3,5-tri-O-benzyl-1,4-anhydro-4-thio-D-arabinitol
      at the C-6 position of benzyl 6-O-p-toluenesulfonyl beta-D-glucopyranoside,
      followed by deprotection using boron trichloride and reduction with sodium
      borohydride. The target compound inhibited the N-terminal catalytic domain of
      intestinal human maltase glucoamylase (ntMGAM) with a K(i) value of 0.50 +/- 0.04
      MUM, higher than those of de-O-sulfonated ponkoranol (K(i)=43 +/- 3 nM), or its
      5'-stereoisomer (K(i)=15 +/- 1 nM). We conclude that the interaction of the
      methyl group with hydrophobic residues in the active site is not as beneficial to
      inhibition of ntMGAM as the other interactions of the polyhydroxylated chain with
      active-site residues.

PMID- 20801034
TI  - Natural product derivatives with bactericidal activity against Gram-positive
      pathogens including methicillin-resistant Staphylococcus aureus and vancomycin
      resistant Enterococcus faecalis.
AB  - We have shown that the intentional engineering of a natural product biosynthesis
      pathway is a useful way to generate stereochemically complex scaffolds for use in
      the generation of combinatorial libraries that capture the structural features of
      both natural products and synthetic compounds. Analysis of a prototype library
      based upon nonactic acid lead to the discovery of triazole-containing nonactic
      acid analogs, a new structural class of antibiotic that exhibits bactericidal
      activity against drug resistant, Gram-positive pathogens including Staphylococcus
      aureus and Enterococcus faecalis.

PMID- 20801035
TI  - Synthesis and biological evaluation of C-2 halogenated analogs of salvinorin A.
AB  - Salvinorin A (1), the main active ingredient of Salvia divinorum, is a potent and
      selective kappa opioid receptor (KOPR) agonist. Based on the SAR, its C-2
      position is one of the key binding sites and has very little space tolerance (3-4
      carbons atoms) and limited to only lipophilic groups. In our attempt to prepare
      PET brain imaging agent for mapping KOPR, a series of C-2 halogenated analogs
      have been synthesized and screened for binding affinity at kappa (KOPR), MU
      (MOPR), and delta (DOPR). These C-2 halogenated analogs with sequential changes
      of atomic radius and electron density serve as excellent molecular probes for
      further investigating the binding pocket at C-2, particularly on the effects of
      alpha verses beta configuration at C-2 position. The results of KOPR binding and
      functional studies reveal beta isomer in general binds better than alpha isomer
      with the exception of iodinated analogs and none of the C-2 halogenated analogs
      shows any improvement of KOPR binding affinity. Interestingly, functional assay
      has characterized that 6b is a partial agonist with E(max) of 46% of the kappa
      receptor full agonist U50,488H at 250 nM (K(i)). We have also observed that the
      affinity to the kappa receptor increases with atomic radius (I>Br>Cl>F) which is
      in good agreement with halogen bonding interactions reported in the literature.

PMID- 20801036
TI  - A general scheme for synthesis of substrate-based polyketide labels for acyl
      carrier proteins.
AB  - A general strategy to enzymatically label acyl carrier proteins (ACPs) of
      polyketide synthases has been developed. Incorporation of a chloromethyl ketone
      or vinyl ketone moiety into polyketide chain elongation intermediate mimics
      allows for the synthesis of CoA adducts. These CoA adducts undergo enzymatic
      reaction with Sfp, a phosphopantetheinyl transferase, to afford labeled CurB
      carrier proteins.

PMID- 20801037
TI  - Synthesis and SAR of 2-aryl-3-aminomethylquinolines as agonists of the bile acid
      receptor TGR5.
AB  - Optimization of a screening hit from uHTS led to the discovery of TGR5 agonist
      32, which was shown to have activity in a rodent model for diabetes.

PMID- 20801038
TI  - Unusual antimalarial meroditerpenes from tropical red macroalgae.
AB  - Three antimalarial meroditerpenes have been isolated from two Fijian red
      macroalgae. The absolute stereochemistry of callophycolide A (1), a unique
      macrolide from Callophycus serratus, was determined using a combination of
      Mosher's ester analysis, circular dichroism analysis with a dimolybdenum
      tetraacetate complex, and conformational analysis using NOEs. In addition, two
      known tocopherols, beta-tocopherylhydroquinone (4) and delta
      tocopherylhydroquinone (5), were isolated from Amphiroa crassa. By oxidizing 5 to
      the corresponding delta-tocopherylquinone (6), antimalarial activity against the
      human malaria parasite Plasmodium falciparum was increased by more than 20-fold.

PMID- 20801039
TI  - 9-Dihydroerythromycins as non-antibiotic motilin receptor agonists.
AB  - A series of 9-dihydroerythromycin A and B analogues with modification of the
      desosamine nitrogen have been synthesized and screened for motilin agonist
      activity, antibiotic activity, tachyphylaxis and hERG channel current inhibition.
      Small alkyl groups resulted in the potency while compounds with a primary or
      secondary amine resulted in the low motilin agonist potency. Several compounds
      were identified as non-antibiotic motilin receptor agonists with minimal
      tachyphylaxis and low hERG interaction.

PMID- 20801040
TI  - Effect of granulocyte-colony stimulating factor on spinal cord tissue after
      experimental contusion injury.
AB  - The purpose of this study was to investigate the early effects of granulocyte
      colony stimulating factor (G-CSF) on myeloperoxidase (MPO) activity, lipid
      peroxidation (LPO) and ultrastructural findings in rats after spinal cord injury
      (SCI). We also compared the effects of G-CSF and methylprednisolone sodium
      succinate (MPSS). Wistar rats were divided into four groups: control, SCI alone
      (50 g/cm weight drop trauma), SCI+MPSS (30 mg/kg), and SCI+G-CSF (50 MUg/kg).
      Administration of G-CSF and MPSS significantly decreased LPO (p < 0.05) and MPO
      activity (p < 0.05) in the first 24 hours. MPSS was more effective than G-CSF in
      reducing LPO (p < 0.05) and in minimizing ultrastructure changes. The results of
      this study indicate that G-CSF exerts a beneficial effect by decreasing MPO
      activity and LPO and may reduce tissue damage in the first 24 hours after SCI.
      Our findings do not exclude the possibility that G-CSF has a protective effect on
      spinal cord ultrastructure after the first 24 hours following SCI.

PMID- 20801041
TI  - Microsurgical management of dumbbell C1 and C2 schwannomas via the far lateral
      approach.
AB  - Dumbbell C1 and C2 schwannomas are rare and have a distinctive presentation and
      anatomical features. To study the clinical characteristics of these tumors, we
      reviewed the microsurgical management of 18 patients with dumbbell C1 and C2
      schwannomas by the far lateral approach. Data regarding clinical manifestations,
      radiological findings and surgical results were analyzed retrospectively. Total
      and subtotal resection of the tumor was achieved in 15 and three patients,
      respectively. At the time of discharge, 12 patients showed improvement while five
      patients remained the same. The average follow-up duration was 43 months (range =
      3-110 months); six of seven patients had recovery from local pain or numbness.
      With the exception of one patient with hemiplegia or hemiparesthesia
      preoperatively, all patients recovered within 6 months postoperatively. The far
      lateral approach offers adequate exposure and access with minimal neural
      manipulation for treating dumbbell C1 and C2 schwannomas, and is considered the
      preferred surgical approach for resection of these tumors located ventrally or
      ventrolaterally to the first two cervical vertebrae.

PMID- 20801042
TI  - A stereological study of MRI and the Cavalieri principle combined for diagnosis
      and monitoring of brain tumor volume.
AB  - In this study, we aimed to describe the application of the Cavalieri principle
      for the assessment of tumor volume using MRI without an over
      projection/estimation effect. For this purpose, the volume of a patient's brain
      and the brain tumor volume, or the volume of the former tumor region, were
      estimated preoperatively and postoperatively using a combination of the Cavalieri
      principle and MRI. The previously described formula was modified for MRI
      measurements to eliminate the over-estimation effects of imaging. The total brain
      and tumor volumes estimated using the MRI of a representative patient with
      glioblastoma multiforme were: preoperative, 1562.46 cm3 and 81.59 cm3,
      respectively; and postoperative, 1571.72 cm3 and 86.92 cm3, respectively. The
      mean time to count points for an estimation of brain and tumor volume (or the
      volume of the former tumor region) were 14 minutes and 3 minutes, respectively.
      The coefficients of the errors of the estimates for brain and tumor volume
      (former tumor volume, postoperative) measurements were: preoperative 0.01 and
      0.02; and postoperative 0.01 and 0.03, respectively. Our results show that the
      combination of MRI and the Cavalieri principle can provide an unbiased, direct
      and assumption-free estimate of the regions of interest. Therefore, the presented
      method could be applied efficiently without any need for special software,
      additional equipment or personnel other than that required for routine MRI in
      daily use.

PMID- 20801043
TI  - CTG repeat lengths of the DMPK gene in myotonic dystrophy patients compared to
      healthy controls in Thailand.
AB  - Myotonic dystrophy (DM) is frequently associated with large expansions of the
      cytosine-thymine-guanine (CTG) repeat in the myotonic dystrophy protein kinase
      gene (DMPK). The frequency of distribution of the CTG repeat length in normal
      alleles of several populations is well correlated with the prevalence of DM.
      Therefore, we studied the CTG repeat length of the DMPK gene in DM patients and
      controls in Thailand. Only seven typical patients with DM from six unrelated
      families were identified, all with large pathological CTG repeat expansions (>
      400 repeats) in the DMPK gene. Only 2.75% of controls had normal CTG repeat
      alleles > 18 repeats. The frequency distribution of the CTG-repeat alleles in the
      normal Thai population is similar to that of the Taiwanese population (chi2 with
      Yates correction = 1.393; p = 0.2379). These data suggest that the incidence of
      DM might be rare in Thailand, where the risk of developing DM is possibly similar
      to that in Taiwan.

PMID- 20801044
TI  - Emerging complex pathways of the actomyosin powerstroke.
AB  - Actomyosin powers muscle contraction and various cellular activities, including
      cell division, differentiation, intracellular transport and sensory functions.
      Despite their crucial roles, key aspects of force generation have remained
      elusive. To perform efficient force generation, the powerstroke must occur while
      myosin is bound to actin. Paradoxically, this process must be initiated when
      myosin is in a very low actin-affinity state. Recent results shed light on a
      kinetic pathway selection mechanism whereby the actin-induced activation of the
      swing of myosin's lever enables efficient mechanical functioning. Structural
      elements and biochemical principles involved in this mechanism are conserved
      among various NTPase-effector (e.g. kinesin-microtubule, G protein exchange
      factor and kinase-scaffold protein) systems that perform chemomechanical or
      signal transduction.

PMID- 20801045
TI  - Predicting dynamic knee joint load with clinical measures in people with medial
      knee osteoarthritis.
AB  - Knee joint loading, as measured by the knee adduction moment (KAM), has been
      implicated in the pathogenesis of knee osteoarthritis (OA). Given that the KAM
      can only currently be accurately measured in the laboratory setting with
      sophisticated and expensive equipment, its utility in the clinical setting is
      limited. This study aimed to determine the ability of a combination of four
      clinical measures to predict KAM values. Three-dimensional motion analysis was
      used to calculate the peak KAM at a self-selected walking speed in 47 consecutive
      individuals with medial compartment knee OA and varus malalignment. Clinical
      predictors included: body mass; tibial angle measured using an inclinometer;
      walking speed; and visually observed trunk lean toward the affected limb during
      the stance phase of walking. Multiple linear regression was performed to predict
      KAM magnitudes using the four clinical measures. A regression model including
      body mass (41% explained variance), tibial angle (17% explained variance), and
      walking speed (9% explained variance) explained a total of 67% of variance in the
      peak KAM. Our study demonstrates that a set of measures easily obtained in the
      clinical setting (body mass, tibial alignment, and walking speed) can help
      predict the KAM in people with medial knee OA. Identifying those patients who are
      more likely to experience high medial knee loads could assist clinicians in
      deciding whether load-modifying interventions may be appropriate for patients,
      whilst repeated assessment of joint load could provide a mechanism to monitor
      disease progression or success of treatment.

PMID- 20801046
TI  - Early complications of medial opening wedge high tibial osteotomy using
      autologous tricortical iliac bone graft and T-plate fixation.
AB  - Despite several advantages of medial opening wedge high tibial osteotomy, this
      procedure has been noted to have a high rate of complications especially with the
      use of a spacer plate for fixation. We retrospectively evaluated the early
      complications of 138 medial opening wedge high tibial osteotomies done using
      autologous tricortical iliac bone graft and T-plate fixation(AO locking
      compression T-plate, Ti/3H 4.5-5.0 mm, Synthes, Switzerland, Model No. 440.131 in
      30 and low-profile locking T-plate and low-profile locking T-plate in 128
      patients. At a mean follow-up of 36.8 months (13 to 78), 26 knees (18.8%)
      developed complications. Complications varied from osteotomy site infection, loss
      of correction, broken screws and lateral tibial plateau fracture to joint fluid
      leakage, pseudoaneurysm and iliac bone fractures. Using the "safe zone" technique
      and penetrating the lateral cortex with Steinmann pins may help to avoid
      complications such as loss of correction and lateral tibial plateau fractures.
      The results of this study indicate that medial opening wedge high tibial
      osteotomy using autologous tricortical iliac bone graft and T-plate fixation may
      be a technically demanding procedure associated with a moderate rate of
      complications. However, these complications could be minimized with proper
      planning, adequate intra-operative precautions and few modifications to avoid
      technical error.

PMID- 20801047
TI  - Preoperative proprioceptive training in patients with total knee arthroplasty.
AB  - Proprioceptive deficiencies due to osteoarthritis and arthroplasty have been
      repeatedly reported. Proprioceptive training, which leads to an economisation of
      movements and supports energy-saving movement patterns, has become popular in
      athletes, but not in rehabilitation yet. The aim of this randomised phase IIb
      study was to evaluate whether preoperative proprioceptive training would
      influence postoperative balance and function in activities of daily life in
      patients undergoing total knee arthroplasty. Subjects with severe osteoarthritis
      of the knee scheduled for TKA were randomised to either a control group (CG) or a
      training group (TG). All patients were examined 6 weeks before and 6 weeks after
      TKA, patients of the TG also one day before surgery, i.e. after six weeks of
      preoperative proprioceptive training, in order to evaluate the influence of
      training without TKA. Evaluation included balance assessment using the Biodex
      Stability System, as well as measurements of gait speed and clinical outcome
      using the WOMAC and Knee Society Score. As opposed to the CG, stance stability
      improved significantly in the TG (Biodex OSI (p=0.045), APSI (p=0.029)) 6 weeks
      after TKA. There was a significant improvement in KSS, WOMAC pain and stiffness
      in both groups after TKA. Preoperative proprioceptive training in patients
      undergoing TKA resulted in improved standing balance, but no difference in
      clinical outcome was observed between the two groups.

PMID- 20801048
TI  - Novel imidazoline compounds as partial or full agonists of D2-like dopamine
      receptors inspired by I2-imidazoline binding sites ligand 2-BFI.
AB  - Based on the well known biological versatility of the imidazoline nucleus, we
      prepared the novel derivatives 3a-k inspired by 2-BFI scaffold to assess
      imidazoline molecules as D(2)-like dopamine receptor ligands. Conservative
      chemical modifications of the lead structure, such as the introduction of an
      hydroxy group in the aromatic ring alone or associated with N-benzyl
      substitution, provided partial (3f) or nearly full (3e and 3h) agonists, all
      endowed with D(2)-like potency comparable to that of dopamine.

PMID- 20801049
TI  - Sucralose sweetener in vivo effects on blood constituents radiolabeling, red
      blood cell morphology and radiopharmaceutical biodistribution in rats.
AB  - Effects of sucralose sweetener on blood constituents labelled with technetium-99m
      ((99m)Tc) on red blood cell (RBC) morphology, sodium pertechnetate
      (Na(99m)TcO(4)) and diethylenetriaminepentaacetic acid labeled with (99m)Tc
      ((99m)Tc-DTPA) biodistribution in rats were evaluated. Radiolabeling on blood
      constituents from Wistar rats was undertaken for determining the activity
      percentage (%ATI) on blood constituents. RBC morphology was also evaluated.
      Na(99m)TcO(4) and (99m)Tc-DTPA biodistribution was used to determine %ATI/g in
      organs. There was no alteration on RBC blood constituents and morphology %ATI.
      Sucralose sweetener was capable of altering %ATI/g of the radiopharmaceuticals in
      different organs. These findings are associated to the sucralose sweetener in
      specific organs.

PMID- 20801050
TI  - Chest-tube digital assessment after pulmonary resection: the crucial role of time
      trend analysis and a new model to predict a persistent air leak.

PMID- 20801051
TI  - Minimizing bleeding associated with mechanical circulatory support following
      pediatric heart surgery.
AB  - OBJECTIVE: The use of extracorporeal membrane oxygenation (ECMO) to support
      patients with early postcardiotomy heart failure may be associated with
      catastrophic bleeding, making its use undesirable. However, postcardiotomy
      mechanical circulatory assistance is necessary in some patients to allow for
      myocardial recovery. We have assembled a centrifugal pump system (CPS) that does
      not require early systemic anticoagulation. This study compares postoperative
      bleeding in pediatric patients placed on standard ECMO versus CPS within 24h of
      cardiotomy. METHODS: Between November 2002 and February 2007, 25 patients (age 0
      days-1.72 years) received postcardiotomy mechanical support. Fourteen patients
      were placed on ECMO and 11 patients were placed on CPS within 24h of surgical
      repair. Retrospective analysis was performed of chest-tube drainage at multiple
      time points following initiation of mechanical support. Additional variables,
      including Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1) score, total
      time on mechanical support, 30-day mortality, activated clotting time, blood
      product administration, circuit-related complications, and circuit changes were
      also analyzed. RESULTS: Patients on ECMO (0.30 +/- 0.39 years) and CPS (0.40 +/-
      0.56 years) were of similar age (p = 0.64). Patients on ECMO (0.3 +/- 0.1m(2))
      and CPS (0.3 +/- 0.1m(2)) had similar body surface areas (p = 0.46). Patients
      placed on CPS had significantly less chest-tube drainage during the first 4h of
      support. Activated clotting times appeared to be higher during the first 12h of
      ECMO versus CPS. There was no statistical difference between ECMO and CPS with
      respect to the following variables: RACHS-1 score, time on support, 30-day
      mortality, circuit-related complications, and circuit changes. Blood-product
      administration at 24h of support was significantly less (p = 0.04) for patients
      on CPS versus ECMO. CONCLUSIONS: Mechanical circulatory support can be provided
      without the complication of clinically significant bleeding if a specialized
      circuit is used. This has important implications for the decision to use
      mechanical support in the immediate postoperative period in the face of
      ventricular failure. In addition, early mechanical support can be used with a low
      incidence of circuit-related complications.

PMID- 20801053
TI  - Anomalous coronary supply from right internal mammary artery.

PMID- 20801054
TI  - Digital measurements of air leak flow and intrapleural pressures in the immediate
      postoperative period predict risk of prolonged air leak after pulmonary
      lobectomy.
AB  - BACKGROUND: The objective of this prospective observational study was to evaluate
      the association between the airflow and intrapleural pressures digitally recorded
      during the immediate postoperative period after lobectomy and their ability to
      predict the risk of subsequent prolonged air leak (PAL). METHODS: A total of 145
      consecutive patients underwent pulmonary lobectomy in two centers. All patients
      were managed with the chest tube placed on suction (-20 cm H(2)O) until the
      morning of the first postoperative day. Measurement of airflow and maximum and
      minimum intrapleural pressures were recorded during the 6th postoperative hour
      using a digital chest drainage device. Logistic regression analysis validated by
      bootstrap was used to test independent association of variables with PAL (air
      leak>72 h). RESULTS: The mean air leak flow at the 6th postoperative hour was 86
      ml min(-1) (0-1100 ml min(-1)). The mean maximum and minimum pleural pressures at
      the 6th postoperative hour were -11.4 cm H(2)O and -21.9 cm H(2)O, respectively.
      Logistic regression and bootstrap showed that the mean air leak flow (p=0.007)
      and the mean differential pleural pressure (DeltaP: maximum-minimum intrapleural
      pressure) (p=0.02) at the 6th postoperative hour were reliably associated with
      PAL, independent of the effect of age, forced expiratory volume 1 (FEV1), chronic
      obstructive pulmonary disease (COPD) status, diffusing capacity of the lung for
      carbon monoxide (DLCO), side, and site of lobectomy. According to best cutoffs
      derived by receiver operating characteristic (ROC) analysis the following
      combinations showed incremental risk of PAL: DeltaP<10+Flow<50: 4% (3/73);
      DeltaP>10+Flow<50: 15% (5/33); DeltaP<10+Flow>50: 36% (5/14); DeltaP>10+Flow>50:
      52% (13/25). CONCLUSIONS: The levels of both air leak flow and pleural pressure
      measured at the 6th postoperative hour are associated to a different extent with
      the duration of air leak. Interpretation of the data measured at an early time
      point by digital chest drainage systems allows estimation of the risk of
      subsequent PAL. In this way, digital devices may help to plan postoperative
      management to allow both safe and more accurate implementation of fast-tracking
      strategies.

PMID- 20801055
TI  - Evaluation of the bioactive and total transforming growth factor beta1 levels in
      primary myelofibrosis.
AB  - TGFbeta1 is secreted as latent protein that requires activation to become
      biologically active. It negatively regulates the progenitor cell growth, and
      favours the deposition of extra-cellular matrix in different tissues. We have
      studied TGFbeta1 levels in Philadelphia-negative (Ph-) myeloproliferative
      diseases, evaluating patients with primary myelofibrosis (PMF) that is
      characterized by increased numbers of circulating progenitor cells and bone
      marrow (BM) fibrosis, and patients with polycythemia vera (PV) or essential
      thrombocythemia (ET) that do not present BM fibrosis. We found that patients with
      PMF, PV or ET have higher peripheral blood (PB) plasma levels of both bioactive
      and total TGFbeta1 than healthy controls, with a balance bioactive/total TGFbeta1
      in favour of the latter. The balance between bioactive/total TGFbeta1 in the BM
      plasma of patients mirrored that of PB, with most of TGFbeta1 in the latent form;
      on the contrary, in the BM plasma of healthy controls most of the TGFbeta1 was in
      the bioactive form. In conclusion, increased plasma levels of TGFbeta1 and an
      altered ratio bioactive/total TGFbeta1 in BM are not peculiar of patients with
      PMF suggesting that, whether altered levels of TGFbeta1 have a role in
      myelofibrosis, this may not be related to the induction of BM fibrosis.

PMID- 20801056
TI  - Quantifying labile protein-ligand interactions using electrospray ionization mass
      spectrometry.
AB  - A new electrospray ionization mass spectrometry (ES-MS) approach for quantifying
      protein-ligand complexes that are prone to in-source (gas-phase) dissociation is
      described. The method, referred to here as the reference ligand ES-MS method, is
      based on the direct ES-MS assay and competitive ligand binding. A reference
      ligand (L(ref)), which binds specifically to the protein (P), at the same binding
      site as the ligand (L) of interest, with known affinity and forms a stable
      protein-ligand complex in the gas phase, is added to the solution. The fraction
      of P bound to L(ref), which is determined directly from the ES mass spectrum, is
      sensitive to the fraction of P bound to L in solution and enables the affinity of
      P for L to be determined. A mathematical framework for the implementation of the
      method in cases where P has one or two specific ligand binding sites is given.
      Affinities of two carbohydrate-binding proteins, a single chain fragment of a
      monoclonal antibody and the lectin concanavalin A, for monosaccharide ligands are
      reported and the results are shown to agree with values obtained using isothermal
      titration calorimetry.

PMID- 20801057
TI  - Redo sternotomy for cardiac reoperations using peripheral heparin-bonded
      cardiopulmonary bypass circuits without systemic heparinization: technique and
      results.
AB  - OBJECTIVE: Cardiac reoperations are challenging and time-consuming and incur a
      high incidence of perioperative complications because of injuries to cardiac
      structures, bleeding, and hemodynamic instability. Some centers are using
      extracorporeal circulation with heparinization at the time of resternotomy, but
      it leads to prolonged anticoagulation, platelet dysfunction, fibrinolysis,
      coagulopathy, and morbidity. The authors routinely perform resternotomy in
      complex surgery with the support of heparinless cardiopulmonary bypass with
      heparin-bonded circuits (HBCs). The authors describe their technique, indication,
      and results. METHODS: The femoral artery or axillary artery and femoral veins are
      cannulated before sternotomy, and cardiopulmonary bypass is instituted using an
      HBC without systemic heparinization. Systemic heparin (200-300 U/kg) is
      administered when all structures are isolated before aortic cross-clamping
      (activated coagulation time >400 seconds). RESULTS: Between 1996 and 2008, 336
      patients underwent redo sternotomy using the HBC for complex cardiac procedures,
      with 29 deaths (8.6% deaths within 30 days). Only 5 (1.5%) of 336 patients
      sustained injury to the right ventricle, aorta, bypass grafts, or ventricular
      fibrillation during re-entry without hemodynamic deterioration; and underwent
      uneventful repair and outcomes. There was no online HBC thrombosis. CONCLUSIONS:
      This study shows that HBC without systemic heparinization during resternotomy can
      be used safely in complex redo cardiac surgery. The heart is completely
      decompressed during the resternotomy, allowing easy dissection, less likely
      injury to vital structures, and less bleeding without compromising the
      hemodynamics.

PMID- 20801058
TI  - Caldesmon over-expression in type 1 diabetic nephropathy.
AB  - Substantial evidence supports a genetic susceptibility to develop nephropathy in
      type 1 diabetes and a key pathogenic role of actin cytoskeleton dysfunction in
      this complication. We previously reported that many cytoskeletal proteins were
      either up- or down-regulated in fibroblast cells from type 1 diabetic (T1DM)
      patients with nephropathy. The gene of one of these proteins, caldesmon, lies in
      a chromosomal region linked to nephropathy and its promoter region contains a
      single nucleotide polymorphism that is associated with nephropathy. Hence, we
      analyzed caldesmon gene and protein expression in cultured fibroblasts from T1DM
      patients with and without nephropathy and from control subjects. Caldesmon gene
      was studied in cells cultured under normal glucose levels by quantitative real
      time RT-PCR. Caldesmon protein isoforms were quantified both under normal and
      high glucose conditions by two-dimensional electrophoresis. Caldesmon gene was
      over-expressed in fibroblasts from diabetic patients with nephropathy, in
      comparison to both those from diabetic patients without nephropathy and those
      from controls. We quantified six caldesmon protein isoforms, two of them were
      increased whereas another one was decreased only in fibroblasts from diabetic
      patients with nephropathy. None of these isoforms showed any difference in their
      relative abundance in response to high glucose. Variable results in response to
      high glucose were observed in the expression of other proteins in the three
      experimental groups. Our data lend further support to an involvement of caldesmon
      in the susceptibility to diabetic nephropathy in type 1 diabetes, independently
      from environmental glucose levels.

PMID- 20801059
TI  - Comparison of some of the physicochemical characteristics of type 2 diabetic and
      normal human bones: a sample study.
AB  - AIM: The aim of this study was to compare some of the physicochemical
      characteristics of type 2 diabetic bones (DBs) and normal bones (NBs). MATERIALS
      AND METHODS: The organic and inorganic parts of human NBs and DBs were separated
      using conventional methods, and their physicochemical characteristics were
      compared using infrared (IR) spectroscopy, sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis, thermogravimetric analysis, X-ray diffraction (XRD), and
      scanning electron microscopy (SEM). RESULTS: The IR spectrum of the collagen part
      of DBs has showed the presence of carbonyl groups, indicating cross-linking in
      the alpha-chain. This was also confirmed by the increased thermal stability (22
      degrees C) in DB collagen. The XRD data of the inorganic part of DBs have
      revealed decreased crystallinity. SEM images of the inorganic part of DBs have
      shown a porous (weak) nature compared to those of NBs, which exhibited a compact
      (healthy) nature. CONCLUSION: The cross-linking in DB collagen molecules and the
      decreased and defective crystallinity in the inorganic portion of DBs might be
      the reasons for the increased risk of fracture among diabetic patients.

PMID- 20801060
TI  - Depression and incident lower limb amputations in veterans with diabetes.
AB  - PROBLEM: Depression is associated with a higher risk of macrovascular and
      microvascular complications and mortality in diabetes, but whether depression is
      linked to an increased risk of incident amputations is unknown. We examined the
      association between diagnosed depression and incident non-traumatic lower limb
      amputations in veterans with diabetes. METHODS: This was a retrospective cohort
      study from 2000-2004 that included 531,973 veterans from the Diabetes
      Epidemiology Cohorts, a national Veterans Affairs (VA) registry with VA and
      Medicare data. Depression was defined by diagnostic codes or antidepressant
      prescriptions. Amputations were defined by diagnostic and procedural codes. We
      determined the HR and 95% CI for incident non-traumatic lower limb amputation by
      major (transtibial and above) and minor (ankle and below) subtypes, comparing
      veterans with and without diagnosed depression and adjusting for demographics,
      health care utilization, diabetes severity and comorbid medical and mental health
      conditions. RESULTS: Over a mean 4.1 years of follow-up, there were 1289 major
      and 2541 minor amputations. Diagnosed depression was associated with an adjusted
      HR of 1.33 (95% CI: 1.15-1.55) for major amputations. There was no statistically
      significant association between depression and minor amputations (adjusted HR
      1.01, 95% CI: 0.90-1.13). CONCLUSIONS: Diagnosed depression is associated with a
      33% higher risk of incident major lower limb amputation in veterans with
      diabetes. Further study is needed to understand this relationship and to
      determine whether depression screening and treatment in patients with diabetes
      could decrease amputation rates.

PMID- 20801061
TI  - Dental caries in diabetes mellitus: role of salivary flow rate and minerals.
AB  - This study was designed to evaluate the possible protective role of salivary
      factors like salivary flow rate and adequate level of calcium, phosphate, and
      fluoride in diabetes mellitus type 2 patients with dental caries. A total of 398
      diabetes mellitus type 2 patients with dental caries and 395 age- and sex-matched
      non-diabetic subjects with dental caries were included as controls, all of whom
      gave informed consent. All subjects were divided into four groups according to
      their age. Decayed, missed, and filled teeth (DMFT) were scored to indicate the
      severity of dental caries. Saliva was collected, flow rate was noted, and
      calcium, phosphate, and fluoride were analyzed. The blood glucose, HbA1c, and
      DMFT indices were found to be significantly high in diabetic patients as compared
      to controls. The salivary flow rate, calcium, phosphate, and fluoride were found
      to be significantly low whereas no significant difference was found in salivary
      magnesium in patients as compared to controls. Optimum salivary flow rate is
      responsible for establishing protective environment against dental caries.
      Adequate level of salivary calcium, phosphate, and fluoride is also involved in
      significant deposition of these minerals in plaque, which greatly reduces the
      development of caries in the adjacent enamel of teeth.

PMID- 20801063
TI  - Chronic blockade of interleukin-1 (IL-1) prevents and attenuates neuropathic pain
      behavior and spontaneous ectopic neuronal activity following nerve injury.
AB  - Neuropathic pain is a chronic pain state resulting from peripheral nerve injury,
      characterized by hyperalgesia and allodynia. We have reported that mice with
      genetic impairment of IL-1 signaling display attenuated neuropathic pain behavior
      and ectopic neuronal activity. In order to substantiate the role of IL-1 in
      neuropathic pain, WT mice were implanted subcutaneously with osmotic micropumps
      containing either IL-1ra or vehicle. Two days following the implantation, two
      models of neuropathic pain were used; partial nerve injury (spinal nerve
      transection, SNT), or complete nerve cut (spinal neuroma model).
      Mechanosensitivity was assessed seven consecutive days following SNT, and on day
      7 recordings of spontaneous ectopic activity were performed. In the spinal nerve
      neuroma model, autotomy scores were recorded up to 35 days. Vehicle-treated mice
      developed significant allodynia and autotomy, and clear ectopic activity (4.1+/
      1.1% of the axons); whereas IL-1ra-treated mice did not display allodynic
      response, displayed delayed onset of autotomy and markedly reduced severity of
      autotomy scores, and displayed reduced spontaneous activity (0.8+/-0.4% of the
      axons). To test whether IL-1 is involved in maintenance of mechanical allodynia,
      a separate group of WT mice was treated with a single injection of either saline
      or IL-1ra four days following SNT, after the allodynic response was already
      manifested. Whereas saline-treated mice displayed robust allodynia, acute IL-1ra
      treatment induced long-lasting attenuation of the allodynic response. The results
      support our hypothesis that IL-1 signaling plays an important role in neuropathic
      pain and in the ectopic neuronal activity that underling its development.

PMID- 20801062
TI  - alpha-Lipoic acid protects diabetic apolipoprotein E-deficient mice from
      nephropathy.
AB  - AIM: Both hyperglycemia and hyperlipidemia increase oxidative stress and
      contribute to the development of diabetic nephropathy (DN). We investigated the
      effects of alpha-lipoic acid, a natural antioxidant and a cofactor in the
      multienzyme complexes, on the development of DN in diabetic apolipoprotein E
      deficient mice. METHODS: Twelve-week-old male apoE-/- mice on C57BL/6J genetic
      background were made diabetic with injections of streptozotocin (STZ). STZ
      treated diabetic apoE-/- mice and non-diabetic control were fed with a synthetic
      high-fat (HF) diet with or without lipoic acid (LA) supplementation. Multiple
      parameters including plasma glucose, cholesterol, oxidative stress markers,
      cytokines, and kidney cortex gene expression, and glomerular morphology were
      evaluated. RESULTS: LA supplementation markedly protected the beta cells, reduced
      cholesterol levels, and attenuated albuminuria and glomerular mesangial expansion
      in the diabetic mice. Renoprotection by LA was equally effective regardless of
      whether the dietary supplementation was started 4 weeks before, simultaneously
      with, or 4 weeks after the induction of diabetes by STZ. LA supplementation
      significantly improved DN and oxidative stress in the diabetic mice. Severity of
      albuminuria was positively correlated with level of thiobarbituric acid reactive
      substances (TBARs) in the kidney (r(2)=0.62, P<.05). Diabetes significantly
      changed the kidney expression of Rage, Sod2, Tgfb1 and Ctgf, Pdp2, nephrin, and
      Lias. LA supplementation corrected these changes except that it further
      suppressed the expression of the Lias gene coding for lipoic acid synthase.
      CONCLUSIONS: Our data indicate that LA supplementation effectively attenuates the
      development and progression of DN through its antioxidant effect as well as
      enhances glucose oxidation.

PMID- 20801064
TI  - Psychological changes and the resolution of acute neck pain after a motor vehicle
      accident.
AB  - This study examines the changes in self-perception during resolution of an
      acutely painful neck injury sustained in a motor vehicle accident. We tested
      predictions from self-discrepancy theory and a model of self-pain enmeshment.
      Measures of discrepancy between the current (actual) self and both the ideal and
      feared-for self were predicted to remain stable over a 21-day recovery period
      whereas a measure of enmeshment was predicted to decrease as pain resolved. We
      also examined the relationship between daily ratings of achievement in several
      domains and participants perceived ideal performance. Sixty patients with
      possible acute neck injury recruited within 1 month after a motor vehicle
      accident gave consent and data were obtained from 42 participants. Standard
      questionnaire measures of pain, disability, fear of movement, pain
      catastrophizing and self-discrepancies, self-pain enmeshment and data from
      diaries (measures of pain, mood, self-discrepancies, pain catastrophizing and
      fear of movement) were obtained. In general the relationships between the
      measures of self-discrepancy and enmeshment and mood were in accord with both
      theoretical predictions and previous observations. Resolution of pain was
      associated with a reduction in enmeshment but not to change in self-discrepancy.
      Multilevel analyses of the diary data showed that concordance between actual and
      ideal performance increased over the 21 days of data collection. These data
      provide preliminary support for aspects of self-discrepancy theory and the self
      pain enmeshment model.

PMID- 20801065
TI  - Filter diagonalization using a "sensitivity-enhanced basis": improved performance
      for noisy NMR spectra.
AB  - The Filter Diagonalization Method (FDM) has been used to process NMR data in
      liquids and can be advantageous when the spectrum is sparse enough, the lines are
      sharp and Lorentzian, raw sensitivity is adequate, and the measured time-domain
      data is short, so that the Fourier Transform spectrum exhibits distorted line
      shapes. Noise can adversely impact resolution and/or frequency accuracy in FDM
      spectral estimates. Paradoxically, more complete data can lead to worse FDM
      spectra if there is appreciable noise. However, by modifying the numerical
      method, the FDM noise performance improves significantly, without apparently
      losing any of the existing advantages. The two key modifications are to adjust
      the FDM basis functions so that matrix elements computed from them have less
      noise contribution on average, and to regularize each dimension of a
      multidimensional spectrum independently. The modifications can be recommended for
      general-purpose use in the case of somewhat noisy, incomplete data.

PMID- 20801066
TI  - An evaluation of the GLYCAM06 and MM3 force fields, and the PM3-D* molecular
      orbital method for modelling prototype carbohydrate-aromatic interactions.
AB  - The structures and interaction energies of 21 binary complexes of fucose and
      glucose with toluene, 3-methylindole or p-hydroxytoluene, evaluated at the DFT-D
      level, are used to judge the accuracy of the GLYCAM06 and MM3 force fields, and
      the PM3-D* molecular orbital method for modelling carbohydrate-arene
      interactions. The accuracy of the DFT-D method is substantiated by comparison
      with high level CCSD(T) calculations on a small number of representative
      complexes. It is found that a correct description of the intermolecular
      dispersive interactions is essential. Both the PM3-D* method and the GYLCAM06
      force field yield interaction energies within 1 kcal mol-1 of the DFT-D values,
      whilst those from the MM3 force field are in error by more than 2 kcal mol-1.

PMID- 20801067
TI  - Effect of high- and low-intensity exercise and metabolic acidosis on levels of
      GH, IGF-I, IGFBP-3 and cortisol.
AB  - OBJECTIVE: The purpose of the present study was to examine the acute hormonal
      response of a short term high-intensity training (HIT) versus a high volume
      endurance training (HVT) and to determine the contribution of the metabolic
      acidosis as a stimulus for possibly different reactions of circulating hGH, IGF
      1, IGFBP-3 and cortisol. DESIGN: Eleven subjects participated in three
      experimental trials separated by one week. Two times subjects performed four 30s
      maximal effort exercise bouts on a cycle ergometer separated by 5 min rest each.
      Before the exercise subjects either received (single-blinded) bicarbonate (HIT
      (B)) or a placebo (HIT (P)). The third exercise trail consisted of a constant
      load exercise for 1h at 50% VO2max (HVT). Venous blood samples were taken under
      resting conditions, 10 min, 60 min and 240 min after each exercise condition to
      determine hGH, IGF-1, IGFBP-3 and cortisol serum concentrations. Capillary blood
      samples were taken to determine lactate concentrations and blood gas parameters.
      RESULTS: Power output, mean lactate concentrations and mean pH values were
      significantly higher during HIT (B) compared to HIT (P). Serum cortisol and hGH
      concentrations were significantly increased 10 min post exercise in both HIT
      interventions. IGFBP-3 was only significantly increased after HIT (P), whereas
      IGF-1 was not affected by any of the interventions. HVT showed no significant
      effects on cortisol, hGH, IGF-1 and IGFBP-3 levels. Additionally it was shown
      that the diminished acidosis during HIT (B) attenuates the cortisol and hGH
      response. CONCLUSIONS: The present study suggests that HIT/acidosis is a stimulus
      for exercise-induced cortisol/hGH secretion, but not for IGF-1 and IGFBP-3 under
      these experimental conditions. These findings might be relevant for arrangements
      of interval training, due to the fact that active or passive recovery during rest
      periods influence the acid base status and may therefore influence the hormonal
      response.

PMID- 20801068
TI  - Differences in the predominance of lysosomal and autophagic pathologies between
      infants and adults with Pompe disease: implications for therapy.
AB  - Pompe disease is a lysosomal storage disorder caused by the deficiency of acid
      alpha-glucosidase, the enzyme that degrades glycogen in the lysosomes. The
      disease manifests as a fatal cardiomyopathy and skeletal muscle myopathy in
      infants; in milder late-onset forms skeletal muscle is the major tissue affected.
      We have previously demonstrated that autophagic inclusions in muscle are
      prominent in adult patients and the mouse model. In this study we have evaluated
      the contribution of the autophagic pathology in infants before and 6 months after
      enzyme replacement therapy. Single muscle fibers, isolated from muscle biopsies,
      were stained for autophagosomal and lysosomal markers and analyzed by confocal
      microscopy. In addition, unstained bundles of fixed muscles were analyzed by
      second harmonic imaging. Unexpectedly, the autophagic component which is so
      prominent in juvenile and adult patients was negligible in infants; instead, the
      overwhelming characteristic was the presence of hugely expanded lysosomes. After
      6 months on therapy, however, the autophagic buildup becomes visible as if
      unmasked by the clearance of glycogen. In most fibers, the two pathologies did
      not seem to coexist. These data point to the possibility of differences in the
      pathogenesis of Pompe disease in infants and adults.

PMID- 20801069
TI  - Ocular motor abnormalities in Parkinsonian syndromes.
AB  - Oculomotor abnormalities can be observed in all Parkinsonian syndromes (PS).
      Nevertheless, due to the considerable overlap of oculomotor pathology in
      Parkinsonism, oculomotor changes are not generally considered to contribute
      substantially to the differential diagnosis of PS. Here we review the
      characteristics of oculomotor disturbances in the major PS, we provide a survey
      of the current concepts of the underlying neural physiology of oculomotor control
      and a summary of the major recording techniques for eye movements. The main focus
      of this review is to outline the subtle differences between apparently similar
      oculomotor alterations in Parkinson's disease (PD) and atypical neurodegenerative
      PS that can contribute to the early differential diagnosis of these entities.

PMID- 20801070
TI  - Authors' replies to the comments of Giugni et al. on "Hiccups in Parkinson's
      disease: an overlooked non-motor symptom?".

PMID- 20801071
TI  - Health impact assessment and evaluation of a Roma housing project in Hungary.
AB  - An outstanding feature of marginalized Roma communities is their severely
      substandard living conditions, which contribute to their worse health status
      compared to the majority. However, health consequences of international and local
      level housing initiatives in most cases fail to be assessed prospectively or
      evaluated after implementation. This paper summarizes the result of a
      retrospective health impact assessment of a Roma housing project in Hungary in
      comparison with the outcome evaluation of the same project. Positive impacts on
      education, in- and outdoor conditions were noted, but negative impacts on social
      networks, housing expenses and maintenance, neighbourhood satisfaction and no
      sustained change in health status or employment were identified. Recommendations
      are made to improve efficiency and sustainability of housing development
      initiatives among disadvantaged populations.

PMID- 20801073
TI  - Sinner Ladies and the gospel of good taste: geographies of food, class and care.
AB  - Set against a background of continuing state, media and public concerns regarding
      obesity, this article examines the media event of the 'Sinner Ladies', in
      Rawmarsh, England. Between 2006 and 2008 three women sparked a controversy that
      illustrates not only the contradictions inherent in health promotion and
      surveillance, especially in relation to diet, parenting and care, but also the
      ways in which such debates touch upon older understandings of social class and
      locality. Healthy eating policies, including those that stress individual
      responsibility, need to be contextualised in the cultures and environments in
      which they are received. Drawing upon notions of health, place, inequality and
      celebrity, we argue that identity and history continue to play a key role in
      competing notions of care in relation to family and food.

PMID- 20801072
TI  - Longitudinal associations between neighborhood-level street network with walking,
      bicycling, and jogging: the CARDIA study.
AB  - OBJECTIVE: To investigate the differential association between neighborhood-level
      street network with walking, bicycling, and jogging by urbanicity and gender.
      METHODS: We used prospective data from 4 repeated exams on 5115 young adults
      recruited in 1985-1986, followed through 2000-2001, with self-reported walking,
      bicycling, and jogging. Using a Geographic Information System, we spatially and
      temporally linked time-varying residential locations to street network data
      within a 1 km Euclidean buffer. Two-part marginal effect modeling assessed
      longitudinal associations between neighborhood-level street network with walking,
      bicycling, and jogging, by urbanicity and gender, controlling for time-varying
      individual- and census-level covariates. RESULTS: Neighborhood street density was
      positively associated with walking, bicycling, and jogging in low urbanicity
      areas, but in middle and high urbanicity areas, these associations became null
      (men) or inverse (women). CONCLUSION: Characteristics of neighborhood streets may
      influence adult residents' walking, bicycling, and jogging, particularly in less
      urban areas. This research may inform policy efforts to encourage physical
      activity.

PMID- 20801074
TI  - Chlorophyll biosynthesis: spotlight on protochlorophyllide reduction.
AB  - Photosynthetic organisms require chlorophyll or bacteriochlorophyll for their
      light trapping and energy transduction activities. The biosynthetic pathways of
      chlorophyll and bacteriochlorophyll are similar in most of their early steps,
      except for the reduction of protochlorophyllide (Pchlide) to chlorophyllide.
      Whereas angiosperms make use of a light-dependent enzyme, cyanobacteria, algae,
      bryophytes, pteridophytes and gymnosperms contain an additional, light
      independent enzyme dubbed dark-operative Pchlide oxidoreductase (DPOR).
      Anoxygenic photosynthetic bacteria such as Rhodobacter capsulatus and Rhodobacter
      sphaeroides rely solely on DPOR. Recent atomic resolution of reductase and
      catalytic components of DPOR from R. sphaeroides and R. capsulatus, respectively,
      have revealed their similarity to nitrogenase components. In this review, we
      discuss the two fundamentally different mechanisms of Pchlide reduction in
      photosynthetic organisms.

PMID- 20801076
TI  - The V-ATPase: small cargo, large effects.
AB  - About 30 years ago seminal reports of anion-sensitive proton-pumping activity
      associated with microsomal membranes initiated research on the plant vacuolar
      type H(+)-ATPase (V-ATPase, VHA). Since, it has been firmly established that
      these complex molecular machines are essential for what can be defined as
      cellular logistics. In a eukaryotic cell, the flow of goods between compartments
      is achieved either by protein-mediated membrane transport or via vesicular
      trafficking. Over the past years, it has become increasingly clear that V-ATPases
      do not only energize secondary active transport but are also important regulators
      of membrane trafficking.

PMID- 20801075
TI  - A general approach to differential sensing using synthetic molecular receptors.
AB  - Differential sensing is continuing to develop as an alternative to traditional,
      selective chemosensing techniques. This technique takes a cue from how the human
      senses of taste and smell operate in order to obtain qualitative and even
      quantitative data on single analytes and mixtures. Whereas classical chemosensing
      techniques inspired by the 'lock-and-key' approach depend on the development of a
      selective receptor for a target analyte, pattern-based sensing depends on the
      development of an array of cross-reactive receptors, which produce a collection
      of responses upon the array's interaction with a target analyte. This review
      focuses on an approach to differential sensing that diversifies synthetic
      receptors to be used in an array via appending combinatorial peptidic arms, metal
      ions, and indicators to a core binding unit.

PMID- 20801077
TI  - Differential resistance to antiviral drugs in an immunocompromised patient with
      cytomegalovirus encephalitis.

PMID- 20801078
TI  - Laboratory evaluation of the new Access (r) cytomegalovirus immunoglobulin IgM
      and IgG assays.
AB  - BACKGROUND: Reliable laboratory methods for detecting congenital CMV infection
      are valuable since CMV infections are asymptomatic and because early detection is
      important for correct management and counseling of expectant mothers. OBJECTIVES:
      Compare the Beckman Coulter Access((r)) method for the Unicel((r)) DxI 800
      analyzer with the bioMerieux VIDAS((r)) method for two serological markers: CMV
      IgG and CMV IgM. STUDY DESIGN: Precision was determined with CLSI EP5-A2
      protocol. Linearity of the Access CMV IgG was evaluated using selected high
      positive samples. Performance was assessed by testing non-selected pregnant
      women, frozen negative and positive samples with recent and old infections.
      Kinetics of the anti-CMV antibodies response was studied using samples from
      pregnant women with a recent infection. In a prospective study, 3992 pregnant
      women were screened for determining prevalence of a primo-infection and CMV IgM
      non-specific rate. RESULTS: Total CV is lower than 10% and 12% for Access CMV IgG
      and CMV IgM. The IgG method is linear (R(2)=0.999) with recoveries between 85%
      and 108%. Correlation between Access and VIDAS CMV IgG is highly significant
      (P<0.001). Observed agreement was 97.4% for CMV IgG and 93.7% for CMV IgM.
      Relative sensitivity and specificity was 97.2% and 100% for IgG and 100% and
      97.4% for IgM. Kinetics of the antibody response measured with Access methods is
      significantly higher (P<0.02) when compared with VIDAS and probably easier to
      interpret. Prevalence of a recent infection was 0.85% and CMV IgM non-specific
      rate was 2.9%. CONCLUSION: Good sensitivity and specificity and pronounced anti
      CMV antibody response make the Access CMV IgG and IgM tests suitable for
      screening prenatal CMV infections.

PMID- 20801079
TI  - The difference between uni- and bilateral auditory phantom percept.
AB  - OBJECTIVE: Tinnitus can be considered an auditory phantom percept, in which
      patients hear an internal sound in the absence of any external sound source,
      mimicking tonal memory. Tinnitus however can be perceived exclusively uni- or
      bilaterally. METHODS: The neurophysiological differences were investigated
      between unilateral and bilateral tinnitus using LORETA source localized resting
      state EEG recordings. RESULTS: The difference between unilateral and bilateral
      tinnitus is reflected by high frequency activity (beta and gamma) in the superior
      prefrontal gurus, right parahippocampus, right angular gyrus and right auditory
      cortex. Unilateral tinnitus is characterized by contralateral beta2 in the
      superior prefrontal gyrus in comparison to bilateral tinnitus, but gamma in
      comparison to non-tinnitus subjects. Bilateral tinnitus has delta activity in the
      ventrolateral prefrontal cortex in comparison to unilateral tinnitus, and
      bilateral beta1 in comparison to non-tinnitus subjects. Bilateral tinnitus is
      also characterized by bilateral frontopolar beta1 activity. CONCLUSIONS:
      Unilateral and bilateral tinnitus can be differentiated based on their resting
      state oscillation patterns: beta3 and gamma-band activity in the superior
      premotor cortex, parahippocampal area and angular gyrus seem to form the core of
      a spatial localization network involved in tinnitus. SIGNIFICANCE: These
      differences should be taken into account when evaluating functional neuroimaging
      data relating to tinnitus.

PMID- 20801080
TI  - Time for universal HIV and HBV screening for patients with cancer.

PMID- 20801081
TI  - Glucocorticoid receptor cofactors as therapeutic targets.
AB  - Numerous transcriptional cofactors (e.g. coactivators, corepressors, and
      comodulators) are known to alter the maximal transcriptional activity (A(max)) in
      gene induction and repression by steroid receptors in general and glucocorticoid
      receptors (GRs) in particular. However, recent data advance the earlier reports
      that these same factors also modify other parameters of glucocorticoid receptor
      transcriptional activity: the potency of agonists (or EC50 and the partial
      agonist activity of antisteroids (or PAA). In several instances, factors modulate
      the EC50 and/or PAA without changing A(max). Thus, studies of all three
      parameters reveal new factors acting at various stages of receptor action,
      thereby increasing the potential therapeutic targets for adjusting GR actions in
      pathological situations.

PMID- 20801082
TI  - Interactions between intestinal compounds of triatomines and Trypanosoma cruzi.
AB  - Triatomine bugs are vectors of Trypanosoma cruzi, the etiologic agent of Chagas
      disease, a devastating disease that disables and leads to the death of many
      people in Latin America. In this review, factors from the insect vector are
      described, including digestive enzymes, hemolysins, agglutinins, microbiota and
      especially antimicrobial factors, which are potentially involved in regulating
      the development of T. cruzi in the gut. Differential regulation of parasite
      populations shows that some triatomine defense reactions discriminate not only
      between molecular signals specific for trypanosome infections but also between
      different strains of T. cruzi.

PMID- 20801083
TI  - Fragile X syndrome prenatal diagnosis: parental attitudes and reproductive
      responses.
AB  - Fragile X syndrome (FXS) is the most common inherited form of mental retardation.
      It is caused by a CGG repeat expansion, which results in hypermethylation and
      silencing of the FMR1 gene. The results from 213 FXS prenatal diagnoses performed
      in the study centre were reviewed. Family history of FXS or undiagnosed mental
      retardation (MR) were the reasons for referral and 64% of mothers were not aware
      of their status so prenatal and mother tests were performed at the same time.
      Among those women referred for family history of unknown MR, 17.6% were found to
      be FXS carriers. The attitudes and perceptions of the syndrome of 52 FXS carriers
      were also evaluated. Most of them had been diagnosed as carriers when the child
      was already born and the most common feeling was sadness, followed by impotence
      and guilt. The majority of them had received genetic counselling and they
      considered it useful. Regarding reproductive options, prenatal diagnosis was
      chosen by 40.5% of women. Prenatal diagnosis for FXS is a good reproductive
      option and it should be carried out whenever family history of MR is present. A
      high percentage of FXS carriers are detected following this approach.

PMID- 20801084
TI  - Possible role of endometriosis in the aetiology of spontaneous miscarriage in
      patients with septate uterus.
AB  - A recent study found a significant correlation between endometriosis and non
      obstructive forms of Mullerian anomalies. Other studies described an increased
      miscarriage rate in patients with endometriosis. This study assessed the effect
      of endometriosis on pregnancy outcome in a group of patients with endometriosis
      and septate uterus. Spontaneously achieved pregnancies were taken into
      consideration. The outcome of 179 infertile women who underwent surgery for
      septate uterus was analysed in a retrospective study. Stage I or II endometriosis
      was found by laparoscopy in 36 patients. The pregnancy outcomes, before and after
      metroplasty, of the group of 36 patients with septum and endometriosis were
      compared with the pregnancy outcomes of 143 patients with septate uterus with no
      endometriosis. Before metroplasty the incidence of pregnancy loss was 67% in
      patients without endometriosis and 75% in patients with endometriosis and the
      difference was not significant. After metroplasty, no significant differences
      have been found between the two groups, suggesting that endometriosis could be an
      occasional finding not influencing pregnancy outcome.

PMID- 20801085
TI  - Treatment of Duchenne muscular dystrophy with ciclosporin A: a randomised, double
      blind, placebo-controlled multicentre trial.
AB  - BACKGROUND: Duchenne muscular dystrophy is a rare X-linked progressive disease
      characterised by loss of ambulation at about age 10 years, with death in early
      adulthood due to respiratory and cardiac insufficiency. Steroids are effective at
      slowing the progression of muscle weakness; however, their use is limited by side
      effects, prompting the search for alternatives. We assessed the effect of
      ciclosporin A as monotherapy and in combination with intermittent prednisone for
      the treatment of ambulant patients with this disorder. METHODS: Our study was a
      parallel-group, placebo-controlled, double-blind, multicentre trial at trial
      sites of the German muscular dystrophy network, MD-NET, over 36 months. Ambulant
      patients with Duchenne muscular dystrophy who were aged 5 years or older were
      randomly assigned to receive either ciclosporin A (3.5-4.0 mg/kg per day) or
      matching placebo. Allocation was done centrally with computer-generated random
      numbers. Patients and investigators were masked to the allocated treatment. After
      3 months of treatment, both groups were also given intermittent prednisone for a
      further 12 months (0.75 mg/kg, alternating 10 days on with 10 days off). All
      patients who received at least one dose of study drug or placebo were included in
      the primary analysis. The primary outcome measure was manual muscle strength
      measured on the Medical Research Council (MRC) scale. This trial is registered
      with the German clinical trial register DRKS, number DRKS00000445. FINDINGS: 77
      patients were randomly assigned to the ciclosporin A group and 76 to the placebo
      group; 73 patients on ciclosporin A and 73 on placebo received at least one dose
      and were available for efficacy analyses. 3 months of treatment with ciclosporin
      A alone did not show any significant improvement in primary outcome measures
      (mean change in the proportion of a possible total MRC score [%MRC] was -2.6 [SD
      6.0] for patients on ciclosporin A and -0.8 [4.9] for patients on placebo;
      adjusted group difference estimate -0.88, 97.5% CI -2.6 to 0.9; p=0.26). The
      combination of ciclosporin A with intermittent steroids was not better than
      intermittent steroids alone over 12 months (mean change in %MRC was 0.7 [7.1] for
      patients on ciclosporin A and -0.3 [7.9] for patients on placebo; adjusted group
      difference estimate -0.85, -3.6 to 1.9; p=0.48). Numbers of adverse events (75 in
      patients on ciclosporin A and 74 on placebo) and serious adverse events (four
      with ciclosporin A and four with placebo) did not differ significantly between
      groups. INTERPRETATION: Ciclosporin A alone or in combination with intermittent
      prednisone does not improve muscle strength or functional abilities in ambulant
      boys with Duchenne muscular dystrophy, but is safe and well tolerated. FUNDING:
      German Federal Ministry of Education and Research, Action Benni and co eV,
      Novartis Pharma AG, and Deutsche Gesellschaft fur Muskelkranke eV.

PMID- 20801086
TI  - Duchenne muscular dystrophy: an important negative trial.

PMID- 20801087
TI  - Antiepileptic action of exogenous dehydroepiandrosterone in iron-induced epilepsy
      in rat brain.
AB  - In the study described here, the antiepileptic effect of dehydroepiandrosterone
      (DHEA) treatment on iron-induced focal epileptiform activity in the rat brain was
      investigated. DHEA is a neuroactive corticosteroid hormone synthesized both in
      the adrenal cortex and in the brain. Its antioxidant properties are well known.
      As oxidative stress seems to play a major role in epileptogenesis in the iron
      induced model of posttraumatic epilepsy, it was of interest to examine whether
      DHEA would exert antiepileptic activity. DHEA at a dose of 30 mg/kg/day
      administered intraperitoneally for 7, 14, and 21 days to iron-induced epileptic
      rats prevented epileptiform electrophysiological activity. Morris water maze and
      open-field tests on iron-induced epileptic rats revealed that DHEA also prevented
      behavioral alterations related to epileptiform activity. Thus, DHEA attenuated
      the cognitive defects produced by epileptic activity. Moreover, alterations in
      epileptogenesis-related biochemical parameters-lipid peroxidation, protein
      oxidation and Na(+), K(+)-ATPase (sodium pump) activity--were also countered by
      DHEA.

PMID- 20801088
TI  - Epilepsy research: occurrences of sudden death in dogs with epilepsy may be
      numbered.

PMID- 20801090
TI  - A simple and sensitive HPLC fluorescence method for determination of tadalafil in
      mouse plasma.
AB  - A simple and sensitive high-performance liquid chromatographic (HPLC) method
      utilizing fluorescence detection was developed for the determination of the
      phosphodiesterase type 5 inhibitor tadalafil in mouse plasma. This method
      utilizes a simple sample preparation (protein precipitation) with high recovery
      of tadalafil (~98%), which eliminates the need for an internal standard. For
      constituent separation, the method utilized a monolithic C(18) column and a flow
      rate of 1.0mL/min with a mobile phase gradient consisting of aqueous
      trifluoroacetic acid (0.1% TFA in deionized water pH 2.2, v/v) and acetonitrile.
      The method calibration was linear for tadalafil in mouse plasma from 100 to
      2000ng/mL (r>0.999) with a detection limit of approximately 40ng/mL. Component
      fluorescence detection was achieved using an excitation wavelength of 275nm with
      monitoring of the emission wavelength at 335nm. The intra-day and inter-day
      precision (relative standard deviation, RSD) values for tadalafil in mouse plasma
      were less than 14%, and the accuracy (percent error) was within -14% of the
      nominal concentration. The method was utilized on mouse plasma samples from
      research evaluating the potential cardioprotective effects of tadalafil on mouse
      heart tissue exposed to doxorubicin, a chemotherapeutic drug with reported
      cardiotoxic effects.

PMID- 20801092
TI  - Frequencies of 33 coding region mitochondrial SNPs in a Danish and a Turkish
      population.

PMID- 20801093
TI  - Croatian Society of PRM and UEMS PRM Section and Board agreement.

PMID- 20801091
TI  - Brain tumor stem cells: the cancer stem cell hypothesis writ large.
AB  - Brain tumors, which are typically very heterogeneous at the cellular level,
      appear to have a stem cell foundation. Recently, investigations from multiple
      groups have found that human as well as experimental mouse brain tumors contain
      subpopulations of cells that functionally behave as tumor stem cells, driving
      tumor growth and generating tumor cell progeny that form the tumor bulk, but
      which then lose tumorigenic ability. In human glioblastomas, these tumor stem
      cells express neural precursor markers and are capable of differentiating into
      tumor cells that express more mature neural lineage markers. In addition,
      modeling brain tumors in mice suggests that neural precursor cells more readily
      give rise to full blown tumors, narrowing potential cells of origin to those
      rarer brain cells that have a proliferative potential. Applying stem cell
      concepts and methodologies is giving fresh insight into brain tumor biology, cell
      of origin and mechanisms of growth, and is offering new opportunities for
      development of more effective treatments. The field of brain tumor stem cells
      remains very young and there is much to be learned before these new insights are
      translated into new patient treatments.

PMID- 20801094
TI  - Elimination of human onchocerciasis: history of progress and current feasibility
      using ivermectin (Mectizan((r))) monotherapy.
AB  - We review and analyze approaches over a 65 year period that have proven
      successful for onchocerciasis control in several different epidemiological
      settings. These include vector control with the goal of transmission interruption
      versus the use of mass drug administration using ivermectin (Mectizan((r)))
      monotherapy. Ivermectin has proven exceedingly effective because it is highly
      efficacious against Onchocerca volvulus microfilariae, the etiological agent of
      onchocercal skin and ocular disease and the infective stage for the vector. For
      these reasons, the drug was donated by the Merck Company for regional control
      programs in Africa and the Americas. Recurrent treatment with ivermectin at semi
      annual intervals also impacts adult worms and result in loss of fecundity and
      increased mortality. Using a strategy of 6-monthly treatments with high coverage
      rates, the Onchocerciasis Elimination Program for the Americas has interrupted
      transmission in seven of the thirteen foci in the Americas and is on track to
      eliminate onchocerciasis in the region by 2015. Treatments given annually or semi
      annually for 15-17 years in three hyperendemic onchocerciasis foci in Mali and
      Senegal also have resulted in a few infections in the human population with
      transmission levels below thresholds postulated for elimination. Follow-up
      evaluations did not detect any recrudescence of infection or transmission,
      suggesting that onchocerciasis elimination could be feasible with Mectizan((r))
      treatment in some endemic foci in Africa.

PMID- 20801095
TI  - Molecular enzymology of lipoxygenases.
AB  - Lipoxygenases (LOXs) are lipid peroxidizing enzymes, implicated in the
      pathogenesis of inflammatory and hyperproliferative diseases, which represent
      potential targets for pharmacological intervention. Although soybean LOX1 was
      discovered more than 60years ago, the structural biology of these enzymes was not
      studied until the mid 1990s. In 1993 the first crystal structure for a plant LOX
      was solved and following this protein biochemistry and molecular enzymology
      became major fields in LOX research. This review focuses on recent developments
      in molecular enzymology of LOXs and summarizes our current understanding of the
      structural basis of LOX catalysis. Various hypotheses explaining the reaction
      specificity of different isoforms are critically reviewed and their pros and cons
      briefly discussed. Moreover, we summarize the current knowledge of LOX evolution
      by profiling the existence of LOX-related genomic sequences in the three kingdoms
      of life. Such sequences are found in eukaryotes and bacteria but not in archaea.
      Although the biological role of LOXs in lower organisms is far from clear,
      sequence data suggests that this enzyme family might have evolved shortly after
      the appearance of atmospheric oxygen on earth.

PMID- 20801096
TI  - Effects of peptide hydrophobicity on its incorporation in phospholipid membranes-
      an NMR and ellipsometry study.
AB  - Effects of peptide hydrophobicity on lipid membrane binding, incorporation, and
      defect formation was investigated for variants of the complement-derived
      antimicrobial peptide CNY21 (CNYITELRRQHARASHLGLAR), in anionic 1-palmitoyl-2
      oleoylphosphatidylethanolamine (POPE)/1-palmitoyl-2-oleoylphosphatidylglycerol
      (POPG) and zwitterionic 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) membranes.
      Using a method combination of, e.g., ellipsometry, CD, and fluorescence
      spectroscopy, it was shown that peptide adsorption, as well as peptide-induced
      liposome leakage and bactericidal potency against Escherichia coli and
      Pseudomonas aeruginosa, was promoted by increasing the hydrophobicity of CNY21
      through either substituting the two histidines (H) in CNY21 with more hydrophobic
      leucine (L) residues, or end-tagging with tritryptophan (WWW). Fluorescence
      spectroscopy revealed that both CNY21WWW and the WWW tripeptide localized to the
      polar headgroup region of these phospholipid membranes. Deuterium NMR experiments
      on macroscopically oriented membranes containing fully (palmitoyl) deuterated
      POPC (POPC-d(31)) demonstrated that both CNY21L and CNY21WWW induced disordering
      of the lipid membrane. In contrast, for cholesterol-supplemented POPC-d(31)
      bilayers, peptide-induced disordering was less pronounced in the case of CNY21L,
      indicating that the peptide is unable to partition to the interior of the lipid
      membrane in the presence of cholesterol. CNY21WWW, on the other hand, retained
      its membrane-disordering effect also for cholesterol-supplemented POPC-d(31).
      These findings were supported by pulsed field gradient NMR experiments where the
      lateral lipid diffusion was determined in the absence and presence of peptides.
      Overall, the results provide some mechanistic understanding to previously
      observed effects of peptide hydrophobization through point mutations and end
      tagging, particularly so for complement-based antimicrobial peptides.

PMID- 20801097
TI  - The Sec translocase.
AB  - The vast majority of proteins trafficking across or into the bacterial
      cytoplasmic membrane occur via the translocon. The translocon consists of the
      SecYEG complex that forms an evolutionarily conserved heterotrimeric protein
      conducting membrane channel that functions in conjunction with a variety of
      ancillary proteins. For posttranslational protein translocation, the translocon
      interacts with the cytosolic motor protein SecA that drives the ATP-dependent
      stepwise translocation of unfolded polypeptides across the membrane. For the
      cotranslational integration of membrane proteins, the translocon interacts with
      ribosome-nascent chain complexes and membrane insertion is coupled to polypeptide
      chain elongation at the ribosome. These processes are assisted by the YidC and
      SecDF(yajC) complex that transiently interacts with the translocon. This review
      summarizes our current understanding of the structure-function relationship of
      the translocon and its interactions with ancillary components during protein
      translocation and membrane protein insertion. This article is part of a Special
      Issue entitled Protein translocation across or insertion into membranes.

PMID- 20801098
TI  - Cyclin D1 blocks the anti-proliferative function of RUNX3 by interfering with
      RUNX3-p300 interaction.
AB  - Transcriptional function of cyclin D1, whose deregulation is frequently observed
      in human cancers, has been suggested to contribute to cancer formation. In the
      present study, we show that cyclin D1 protein inhibits RUNX3 activity by directly
      binding to it and interfering with its interaction with p300 interaction in lung
      cancer cells. Cyclin D1 inhibits p300-dependent RUNX3 acetylation and negatively
      regulates cyclin-dependent kinase (cdk) inhibitor p21 expression. These
      transcriptional effects of cyclin D1 do not require cdk4/6 kinase activation. We
      propose that cyclin D1 provides a transcriptional switch that allows the tumor
      suppressor activity of RUNX3 to be repressed in cancer cells. Since RUNX3 plays
      tumor suppressive roles in a wide range of cancers, a non-canonical cyclin D1
      function may be critical for neoplastic transformation of the epithelial cells in
      which RUNX3 regulates proliferation.

PMID- 20801099
TI  - Microparticles mediate enzyme transfer from platelets to mast cells: a new
      pathway for lipoxin A4 biosynthesis.
AB  - The inflammation-resolving lipid mediator lipoxin A4 (LXA4), which is derived
      from arachidonic acid in the context of inflammation, can be generated
      physiologically in vivo. However, the mechanism of physiologic formation of LXA4
      remains elusive. In this report, we provide evidence that platelet-derived
      microparticles contain lipoxygenase 12 (12-LO) protein and act as a mediator in
      transferring 12-LO to mast cells, leading to the production of LXA4 by mast
      cells. Absence of either leukotriene, the precursor for LXA4, in mast cells or 12
      LO in microparticles abolished LXA4 production. Using a mouse model, we
      demonstrated that platelet-derived microparticles were taken up by peritoneal
      mast cells in vivo and triggered LXA4 production. We also found that similar to
      LXA4, platelet-derived microparticles attenuated LPS- or dextran sulfate sodium
      induced inflammation by regulating inflammatory cytokines. Together, these data
      suggest a critical role of platetlet-derived microparticles as a signal mediator,
      at least in LXA4 production, resulting in significant immunoregulatory
      consequences.

PMID- 20801100
TI  - Amyloid formation and disaggregation of alpha-synuclein and its tandem repeat
      (alpha-TR).
AB  - The aggregation of alpha-synuclein is clearly related to the pathogenesis of
      Parkinson's disease. Therefore, detailed understanding of the mechanism of fibril
      formation is highly valuable for the development of clinical treatment and also
      of the diagnostic tools. Here, we have investigated the interaction of alpha
      synuclein with ionic liquids by using several biochemical techniques including
      Thioflavin T assays and transmission electron microscopy (TEM). Our data shows a
      rapid formation of alpha-synuclein amyloid fibrils was stimulated by 1-butyl-3
      methylimidazolium bis(trifluoromethylsulfonyl)imide [BIMbF(3)Im], and these
      fibrils could be disaggregated by polyphenols such as epigallocatechin gallate
      (EGCG) and baicalein. Furthermore, the effect of [BIMbF(3)Im] on the alpha
      synuclein tandem repeat (alpha-TR) in the aggregation process was studied.

PMID- 20801101
TI  - Deacetylase inhibitor trichostatin A down-regulates Foxp3 expression and reduces
      CD4+CD25+ regulatory T cells.
AB  - The forkhead transcription factor Foxp3 is essential for the development and
      function of CD4+CD25+ regulatory T (Treg) cells, which act to maintain immune
      tolerance and prevent autoimmunity. Lysine acetylation that is regulated by
      lysine acetyltransferases and lysine deacetylases plays an important role in gene
      transcription and protein function. Lysine deacetylase inhibitor trichostatin A
      (TSA) is reported to up-regulate Foxp3 expression and increase the generation of
      CD4+CD25+ Treg cells in vivo. In contrast, we found that TSA dramatically reduced
      the levels of Foxp3 mRNA and protein in vitro. Moreover, TSA enhanced the
      activity of the Foxp3 promoter but increased the decay of Foxp3 mRNA.
      Furthermore, administration of TSA significantly impaired the expression of Foxp3
      and reduced the number of CD4+CD25+Foxp3+ Treg cells in C57BL/6J mice. Thus, our
      results show that TSA reduces the expression of Foxp3 through induction of mRNA
      degradation in vitro. Accordingly, TSA decreases Foxp3 expression and reduces the
      number of Treg cells in vivo. Our results are not in agreement with previous
      reports, which are discussed.

PMID- 20801102
TI  - Mel-18, a mammalian Polycomb gene, regulates angiogenic gene expression of
      endothelial cells.
AB  - Mel-18 is a mammalian homolog of Polycomb group (PcG) genes. Microarray analysis
      revealed that Mel-18 expression was induced during endothelial progenitor cell
      (EPC) differentiation and correlates with the expression of EC-specific protein
      markers. Overexpression of Mel-18 promoted EPC differentiation and angiogenic
      activity of ECs. Accordingly, silencing Mel-18 inhibited EC migration and tube
      formation in vitro. Gene expression profiling showed that Mel-18 regulates
      angiogenic genes including kinase insert domain receptor (KDR), claudin 5, and
      angiopoietin-like 2. Our findings demonstrate, for the first time, that Mel-18
      plays a significant role in the angiogenic function of ECs by regulating
      endothelial gene expression.

PMID- 20801103
TI  - Characterization of WbiQ: An alpha1,2-fucosyltransferase from Escherichia coli
      O127:K63(B8), and synthesis of H-type 3 blood group antigen.
AB  - Escherichia coli O127:K63(B8) possesses high human blood group H (O) activity due
      to its O-antigen repeating unit structure. In this work, the wbiQ gene from E.
      coli O127:K63(B8) was expressed in E. coli BL21 (DE3) and purified as a fusion
      protein containing an N-terminal GST affinity tag. Using the GST-WbiQ fusion
      protein, the wbiQ gene was identified to encode an alpha1,2-fucosyltransferase
      using a radioactivity based assay, thin-layer chromatography assay, as well
      confirming product formation by using mass spectrometry and NMR spectroscopy. The
      fused enzyme (GST-WbiQ) has an optimal pH range from 6.5 to 7.5 and does not
      require the presence of a divalent metal to be enzymatically active. WbiQ
      displays strict substrate specificity, displaying activity only towards acceptors
      that contain Gal-beta1,3-GalNAc-alpha-OR linkages; indicating that both the Gal
      and GalNAc residues are vital for enzymatic activity. In addition, WbiQ was used
      to prepare the H-type 3 blood group antigen, Fuc-alpha1,2-Gal-beta1,3-GalNAc
      alpha-OMe, on a milligram scale.

PMID- 20801104
TI  - Association study of polymorphisms in the promoter region of DRD4 with
      schizophrenia, depression, and heroin addiction.
AB  - This study investigated the possible association between three functional
      polymorphisms in the promoter region of the dopamine D4 receptor (DRD4) gene and
      schizophrenia, depression, and heroin addiction. Genomic DNA was isolated from
      the venous blood leukocytes of 322 unrelated patients with schizophrenia, 156
      patients with depression, 300 patients with heroin addiction, and 300 healthy
      unrelated individuals. Polymorphisms in the promoter region of DRD4 (-120 bp
      duplication, -616C/G, and -521C/T) were genotyped using allele-specific
      polymerase chain reaction analysis. Genotype and allele were analyzed using SPSS
      11.5 software. Results of this analysis indicated that there is a strong finding
      of -120 bp duplication allele frequencies with schizophrenia (p=0.008) and weak
      finding with -1240 L/S and for paranoid schizophrenia (p=0.022). Interestingly,
      there is a stronger finding with -521 C/T allele frequencies with heroin
      dependence (p=0.0002). These observations strongly suggest that the -120-bp
      duplication polymorphism of DRD4 is associated with schizophrenia and that the 
      521 C/T polymorphism is associated with heroin addiction.

PMID- 20801105
TI  - Projections from the hypothalamic paraventricular nucleus and the nucleus of the
      solitary tract to prechoroidal neurons in the superior salivatory nucleus:
      Pathways controlling rodent choroidal blood flow.
AB  - Using intrachoroidal injection of the transneuronal retrograde tracer
      pseudorabies virus (PRV) in rats, we previously localized preganglionic neurons
      in the superior salivatory nucleus (SSN) that regulate choroidal blood flow
      (ChBF) via projections to the pterygopalatine ganglion (PPG). In the present
      study, we used higher-order transneuronal retrograde labeling following
      intrachoroidal PRV injection to identify central neuronal cell groups involved in
      parasympathetic regulation of ChBF via input to the SSN. These prominently
      included the hypothalamic paraventricular nucleus (PVN) and the nucleus of the
      solitary tract (NTS), both of which are responsive to systemic BP and are
      involved in systemic sympathetic vasoconstriction. Conventional pathway tracing
      methods were then used to determine if the PVN and/or NTS project directly to the
      choroidal subdivision of the SSN. Following retrograde tracer injection into SSN
      (biotinylated dextran amine 3K or Fluorogold), labeled perikarya were found in
      PVN and NTS. Injection of the anterograde tracer, biotinylated dextran amine 10K
      (BDA10K), into PVN or NTS resulted in densely packed BDA10K+terminals in
      prechoroidal SSN (as defined by its enrichment in nitric oxide synthase
      containing perikarya). Double-label studies showed these inputs ended directly on
      prechoroidal nitric oxide synthase-containing neurons of SSN. Our study thus
      establishes that PVN and NTS project directly to the part of SSN involved in
      parasympathetic vasodilatory control of the choroid via the PPG. These results
      suggest that control of ChBF may be linked to systemic blood pressure and central
      control of the systemic vasculature.

PMID- 20801106
TI  - Von Economo neurons in autism: a stereologic study of the frontoinsular cortex in
      children.
AB  - The presence of von Economo neurons (VENs) in the frontoinsular cortex (FI) has
      been linked to a possible role in the integration of bodily feelings, emotional
      regulation, and goal-directed behaviors. They have also been implicated in fast
      intuitive evaluation of complex social situations. Several studies reported a
      decreased number of VENs in neuropsychiatric diseases in which the "embodied"
      dimension of social cognition is markedly affected. Neuropathological analyses of
      VENs in patients with autism are few and did not report alterations in VEN
      numbers. In this study we re-evaluated the possible presence of changes in VEN
      numbers and their relationship with the diagnosis of autism. Using a stereologic
      approach we quantified VENs and pyramidal neurons in layer V of FI in postmortem
      brains of four young patients with autism and three comparably aged controls. We
      also investigated possible autism-related differences in FI layer V volume.
      Patients with autism consistently had a significantly higher ratio of VENs to
      pyramidal neurons (p=0.020) than control subjects. This result may reflect the
      presence of neuronal overgrowth in young patients with autism and may also be
      related to alterations in migration, cortical lamination, and apoptosis. Higher
      numbers of VENs in the FI of patients with autism may also underlie a heightened
      interoception, described in some clinical observations.

PMID- 20801107
TI  - Mechanism of K(v)2.1 channel inhibition by a selective COX-2 inhibitor SC-791
      modification of gating.
AB  - Recent research suggests that some clinical effects of coxibs, selective
      inhibitors of cyclooxygenase-2 (COX-2), can be mediated via modulation of ion
      channels. It has been shown that clinically relevant concentrations of celecoxib
      can cause inhibition or augmentation of various ionic currents and alter
      functioning of neurons and myocytes. Independence of these effects from
      inhibition of cyclooxygenases raises an important question if other structurally
      related COX-2 inhibitors can affect ion channels in similar fashion. Here we
      studied effects of SC-791, a highly selective COX-2 inhibitor, on K(v)2.1
      channels expressed in HEK-293 cells. SC-791 reversibly inhibited K(v)2.1 in
      voltage-dependent manner with stronger inhibition at negative potentials. The
      values of IC50 were 1.8 MUM and 7.2 MUM for suppression of peak current at -20
      and +40 mV, respectively. The current was reduced via acceleration of
      inactivation, hyperpolarizing shift in the half-inactivation potential and a
      large depolarizing shift in the half-activation potential. In addition, SC-791
      accelerated all other aspects of K(v)2.1 kinetics: activation, deactivation and
      recovery from inactivation. Our results show that SC-791 modified K(v)2.1 gating,
      but, unlike celecoxib, did not induce channel block. These findings help to
      understand the mechanisms of unanticipated action of COX-2 inhibitors on voltage
      activated potassium channels and their physiological implications.

PMID- 20801108
TI  - Diffusible, membrane-bound, and extracellular matrix factors from olfactory
      ensheathing cells have different effects on the self-renewing and differentiating
      properties of neural stem cells.
AB  - Transplantation of olfactory ensheathing cells (OECs) has been a promising
      strategy in enhancing central nervous system (CNS) regeneration. However, little
      is known about the effects of transplanted OECs on the self-renewal,
      neurogenesis, and oligodendrogenesis of neural stem cells (NSCs), which are known
      to play a very important role in the repair of damaged CNS tissue. In this study,
      we investigated the influence of diffusible, membrane-bound, and extracellular
      matrix factors from OECs on the self-renewal and differentiation properties of
      NSCs. We found that diffusible factors from cultured OECs promoted self-renewal,
      whereas the extracellular matrix molecules from OECs increased neurogenesis and
      oligodendrogenesis of NSCs. Furthermore, we demonstrated that directly
      coculturing OECs and NSCs inhibited not only self-renewal but also neurogenesis
      and oligodendrogenesis of NSCs. We propose three models for the interaction
      between transplanted OECs and endogenous NSCs. Our findings provide new insight
      into the ability of OECs to promote CNS repair and also indicate potential
      targets for manipulation of these cells to enhance their restorative ability.

PMID- 20801109
TI  - Anomalous observations of hydrocodone in patients on oxycodone.
AB  - BACKGROUND: Urine drug monitoring is used by physicians treating chronic pain
      patients with opioid therapy. Patients are tested in part to insure that they are
      not taking other drugs. Therefore, the finding of hydrocodone in a patient who is
      only prescribed oxycodone has clinical implications. Oxycodone preparations are
      known to have small amounts of hydrocodone as an impurity estimated to be < 0.1%.
      We established the concentration of unexpected hydrocodone in patients taking
      oxycodone. METHODS: Urine drug testing specimens from a population of 30,000 pain
      patients prescribed oxycodone in various formulations were quantitatively
      measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The
      frequency and concentration of hydrocodone as a function of oxycodone
      concentration were determined. RESULTS: There were 187 specimens with > 100,000
      ng/ml of oxycodone. Of these, 72% were positive for hydrocodone. Of the 311
      specimens with oxycodone concentrations > 50,000-100,000 ng/ml, 33% were positive
      for hydrocodone. Of the 1067 specimens with oxycodone > 20,000-50,000 ng/ml, 16%
      were positive for hydrocodone. Of the 8508 specimens with oxycodone > 1000-20,000
      ng/ml, 16% were positive for hydrocodone. CONCLUSIONS: The high frequency of
      hydrocodone in samples containing high concentrations of oxycodone was ascribed
      to the manufacturing process of the oxycodone medications. However, a significant
      number of patients also took hydrocodone that was not listed on their prescribed
      medications. When oxycodone is > 100,000 ng/ml, hydrocodone should be <1500
      ng/ml. When oxycodone is < 100,000 ng/ml then hydrocodone should be <500 ng/ml.
      Values greater than these indicate non-prescribed hydrocodone use. Clinicians and
      laboratories testing urine for drugs should be aware of the possibility of low
      concentrations of hydrocodone in the urine of patients taking high doses of
      oxycodone.

PMID- 20801110
TI  - Undetectable AMH at 3 days of age: a clue to bilateral anorchia.
AB  - We report the case of a newborn boy who presented with micropenis and bilateral
      cryptorchidism at birth. The determination of AMH level strongly suggested a
      diagnosis of bilateral anorchia at 3 days of age whereas FSH and LH levels at the
      same time were not informative. The rapidity and reliability of results can
      reduce parental anxiety and avoid more invasive explorations.

PMID- 20801111
TI  - Sumoylation controls retinal progenitor proliferation by repressing cell cycle
      exit in Xenopus laevis.
AB  - Precisely controlled progenitor proliferation is essential for normal
      development. However, molecular mechanisms, which control the correct timing of
      cell cycle withdrawal during development, have been poorly understood. We show
      here that ubc9, a sumo-conjugating enzyme, controls the cell cycle exit of
      retinal progenitors. We found that ubc9 is highly expressed in retinal
      progenitors and stem cells in Xenopus embryos. Ubc9 physically and functionally
      associates with Xenopus hmgb3, which is required for retinal cell proliferation,
      and prolonged expression of ubc9 and hmgb3 results in suppression of the cell
      cycle exit of retinal progenitors in a sumoylation-dependent manner.
      Overexpression of ubc9 and hmgb3 decreased expression of the cell-cycle inhibitor
      p27(Xic1). Furthermore, progenitor proliferation is regulated, at least in part,
      by sumoylation of transcription factor Sp1. These results suggest a significant
      role of sumoylation for cell cycle regulation in retinal progenitors.

PMID- 20801113
TI  - Retinol dehydrogenases (RDHs) in the visual cycle.
AB  - The isomerization of 11-cis retinal to all-trans retinal in photoreceptors is the
      first step in vision. For photoreceptors to function in constant light, the all
      trans retinal must be converted back to 11-cis retinal via the enzymatic steps of
      the visual cycle. Within this cycle, all-trans retinal is reduced to all-trans
      retinol in photoreceptors and transported to the retinal pigment epithelium
      (RPE). In the RPE, all-trans retinol is converted to 11-cis retinol, and in the
      final enzymatic step, 11-cis retinol is oxidized to 11-cis retinal. The first and
      last steps of the classical visual cycle are reduction and oxidation reactions,
      respectively, that utilize retinol dehydrogenase (RDH) enzymes. The visual cycle
      RDHs have been extensively studied, but because multiple RDHs are capable of
      catalyzing each step, the exact RDHs responsible for each reaction remain
      unknown. Within rods, RDH8 is largely responsible for the reduction of all-trans
      retinal with possible assistance from RDH12. retSDR1 is thought to reduce all
      trans retinal in cones. In the RPE, the oxidation of 11-cis retinol is carried
      out by RDH5 with possible help from RDH11 and RDH10. Here, we review the
      characteristics of each RDH in vitro and the findings from knockout models that
      suggest the roles for each in the visual cycle.

PMID- 20801112
TI  - Growth differentiation factor 11 signaling controls retinoic acid activity for
      axial vertebral development.
AB  - Mice deficient in growth differentiation factor 11 (GDF11) signaling display
      anterior transformation of axial vertebrae and truncation of caudal vertebrae.
      However, the in vivo molecular mechanisms by which GDF11 signaling regulates the
      development of the vertebral column have yet to be determined. We found that
      Gdf11 and Acvr2b mutants are sensitive to exogenous RA treatment on vertebral
      specification and caudal vertebral development. We show that diminished
      expression of Cyp26a1, a retinoic acid inactivating enzyme, and concomitant
      elevation of retinoic acid activity in the caudal region of Gdf11(-/-) embryos
      may account for this phenomenon. Reduced expression or function of Cyp26a1
      enhanced anterior transformation of axial vertebrae in wild-type and Acvr2b
      mutants. Furthermore, a pan retinoic acid receptor antagonist (AGN193109) could
      lessen the anterior transformation phenotype and rescue the tail truncation
      phenotype of Gdf11(-/-) mice. Taken together, these results suggest that GDF11
      signaling regulates development of caudal vertebrae and is involved in
      specification of axial vertebrae in part by maintaining Cyp26a1 expression, which
      represses retinoic acid activity in the caudal region of embryos during the
      somitogenesis stage.

PMID- 20801114
TI  - The case for autoimmunity in glaucoma.
AB  - Although the majority of patients with glaucoma have elevated intraocular
      pressure as the presumed etiology for their resultant neuropathy, it is well
      known that approximately 25% of patients with glaucoma have intraocular pressure
      within the normal range for their race. These patients may have conditions that
      facilitate non-pressure related stress to the retina and optic nerve that might
      directly contribute to their glaucomatous neuropathy and include chronic or
      intermittent ischemia (i.e atherosclerosis, heart disease, vasospasm, migraine,
      sleep apnea), altered scleral/optic nerve head morphology that predisposes to
      glaucomatous stress (i.e myopia); genetic mutations that predispose to glaucoma
      damage at normal IOP (OPA-1,optineurin, myocilin) and evidence of aberrant
      immunity that suggests that their glaucoma might be a form of an autoimmune
      neuropathy (i.e. presumed autoimmune glaucoma). This review provides a critical
      assessment of the potential role for autoimmunity as an initiating or
      exacerbating etiology in some patients with glaucoma.

PMID- 20801115
TI  - Dopaminergic agonists that result in ocular growth inhibition also elicit
      transient increases in choroidal thickness in chicks.
AB  - The dopaminergic system has been implicated in ocular growth regulation in chicks
      and monkeys. In both, dopamine D2 agonists inhibit the development of myopia in
      response to form deprivation, and in chicks, to negative lenses as well. Because
      there is mounting evidence that the choroidal response to defocus plays a role in
      ocular growth regulation, we asked whether the effective agonists also elicit
      transient thickening of the choroid concomitant with the growth inhibition.
      Negative lenses mounted on velcro rings were worn on one eye starting at age 8-12
      days. Intravitreal injections (20 MUl; dose = 10 nmole) of the agonist (dissolved
      in saline) or saline, were given through the superior temporal sclera using a 30G
      needle. Eyes were injected daily at noon, for 4 days, and the lenses immediately
      replaced. Agonists used were apomorphine (non-specific; n = 17), quinpirole (D2;
      n = 10), SKF-38393 (D1; n = 9), and saline controls (n = 22). For the
      antagonists, the same protocol was used, but on each day, the lenses were removed
      for 2 h. Immediately prior to lens-removal, the antagonist was injected (20 MUl;
      dose = 5 nmole). Antagonists used were methylergonovine (non-specific; n = 12),
      spiperone (D2; n = 20), SCH-23390 (D1; n = 6) and saline controls (n = 27).
      Comparisons to saline (continuous lens wear) controls were from the agonist
      experiment. Axial dimensions were measured using high frequency A-scan
      ultrasonography at the start of lens wear, and on day 4 prior to the injections,
      and then again 3 h later. Refractive errors were measured using a Hartinger's
      refractometer at the end of the experiment. Apomorphine and quinpirole inhibited
      the refractive response to the hyperopic defocus induced by the negative lenses
      (drug vs saline controls: -1.3 and 1.2 D vs -5.6 D; p < 0.005 for both). This
      effect was axial: both drugs prevented the excessive ocular elongation (change in
      axial length: 233 and 205 MUm vs 417 MUm; p < 0.01 for both). Both drugs were
      also associated with a transient thickening of the choroid over 3 h (41 and 32
      MUm vs -1 MUm; p < 0.01; p = 0.059 respectively) that did not summate: choroids
      thinned significantly over the 4 day period in all lens-wearing eyes. Two daily
      hours of unrestricted vision during negative lens wear normally prevents the
      development of myopia. Spiperone and SCH-23390 inhibited the ameliorating effects
      of periods of vision on lens-induced refractive error (-2.9 and -2.8 D vs 0.6 D;
      p < 0.0001), however, the effects on neither axial length nor choroidal thickness
      were significant. These data support a role for both D1 and D2 receptors in the
      ocular growth responses.

PMID- 20801116
TI  - Migratory route of Strongyloides venezuelensis in Lewis rats: comparison of
      histological analyses and PCR.
AB  - Strongyloides venezuelensis is a parasitic nematode that has been used as a model
      to study human and animal strongyloidiasis. In this study, we compared the
      sensitivity between traditional methodologies and PCR assay to characterize the
      dynamics of S. venezuelensis infection and its migration route in Lewis rats
      subcutaneously infected with 4000 L3. The dynamics of the infection was
      determined by counting the number of eggs and by detecting parasite
      deoxyribonucleic acid in faeces samples. Both techniques similarly detected the
      infection at day 6 after larvae inoculation. However, PCR performed with the
      genus primer showed higher sensitivity during the recovery phase. Histological
      analysis and PCR assay were then used to follow parasite tissue migration. S.
      venezuelensis migration route included the muscular fibers below the skin, the
      pulmonary alveoli and the small intestine vilosities. The sensitivity of these
      two techniques to detect parasite's presence in these tissues was statistically
      similar.

PMID- 20801117
TI  - The role of Pvs28 in sporozoite development in Anopheles sinensis and its
      longevity in BALB/c mice.
AB  - To develop a vivax malaria vaccine for blocking malarial transmission, the
      ookinete surface protein Pvs28 was cloned from Korean malaria patients using
      polymerase chain reaction. The Pvs28 gene consists of 726bp and encodes 241 amino
      acids. It was subcloned into the expression vector pQE30 and expressed in
      Escherichia coli. The expressed recombinant protein, rPvs28, has a molecular
      weight of about 28 kDa in SDS-PAGE analysis. A monoclonal antibody against rPvs28
      was produced using BALB/c mice. It inhibited sporozoite development in Anopheles
      sinensis mosquitoes (n = 81) which is one of the malaria vectors in Korea, with
      relatively high antibody titer against rPv28 persisting for more than 6 months.
      These results indicate that rPvs28 induces an immune response in mice that
      effectively blocks sporozoite development in mosquitoes. Therefore it could be a
      vaccine candidate for preventing vivax malaria in Korea.

PMID- 20801118
TI  - Dysfunctional gastric emptying with down-regulation of muscle-specific microRNAs
      in Helicobacter pylori-infected mice.
AB  - BACKGROUND & AIMS: Little is known about the pathogenic mechanisms of functional
      dyspepsia. We investigated the role of microRNAs (miRNAs) in gastric motility
      disorders associated with Helicobacter pylori infection. METHODS: Male C57BL/6
      mice were infected with H pylori. After long-term infection, gastric emptying was
      examined and compared with that of uninfected mice (controls). The miRNA
      expression profile was analyzed by miRNA microarray and quantitative reverse
      transcriptase polymerase chain reaction. The results obtained from the animal
      study were confirmed by in vitro experiments. RESULTS: Gastric emptying was
      significantly accelerated in mice after chronic infection with H pylori.
      Histologic examination showed that the muscular layers of the stomachs of H
      pylori-infected mice were significantly thickened. The miRNA expression profile
      revealed that the muscle-specific miRNAs miR-1 and miR-133 were significantly
      down-regulated in the stomachs after long-term infection with H pylori. However,
      expression of histone deacetylase 4 and serum response factor, which are reported
      target genes of miR-1 and miR-133, increased. Down-regulation of miR-1 and miR
      133 and increased cell proliferation were observed in C2C12 mouse myoblast cells
      after coculture with H pylori. CONCLUSIONS: Chronic infection with H pylori down
      regulates expression of muscle-specific miRNAs and up-regulates expression of
      histone deacetylase 4 and serum response factor. These might cause hyperplasia in
      the muscular layer of the stomach and dysfunction in gastric emptying. These
      findings provide insight into the molecular pathogenesis of gastric motility
      disorders, including functional dyspepsia.

PMID- 20801120
TI  - Proton pump inhibitor therapy improves symptoms in postnasal drainage.
AB  - BACKGROUND & AIMS: Gastroesophageal reflux is common among patients with
      postnasal drainage. We investigated whether proton pump inhibitor therapy
      improved symptoms in patients with postnasal drainage without sinusitis or
      allergies. METHODS: In a parallel-group, double-blind, multi-specialty trial, we
      randomly assigned 75 participants with continued symptoms of chronic postnasal
      drainage to groups that were given 30 mg of lansoprazole twice daily or placebo.
      Participants were followed up for 16 weeks. Symptoms were assessed at baseline
      and after 8 and 16 weeks. Ambulatory pH and impedance monitoring assessed
      presence of baseline reflux. The primary objective of the study was to determine
      if acid suppressive therapy improved postnasal drainage symptoms. The secondary
      objective was to assess if pH and impedance monitoring at baseline predicted
      response to treatment. RESULTS: Postnasal drainage symptoms improved
      significantly among patients given lansoprazole compared with placebo. After 8
      and 16 weeks, participants given lansoprazole were 3.12-fold (1.28-7.59) and 3.50
      fold (1.41-8.67) more likely to respond, respectively, than participants given
      placebo. After 16 weeks, median (interquartile) percent symptom improvements were
      50.0% (10.0%-72.0%) for participants given lansoprazole and 5.0% (0.0%-40.0%) for
      participants given placebo (P = .006). Neither baseline presence of typical
      reflux symptoms nor esophageal physiologic parameters predicted response to
      therapy. CONCLUSIONS: Among participants with chronic postnasal drainage without
      evidence of sinusitis and allergies, twice-daily therapy with proton pump
      inhibitors significantly improved symptoms after 8 and 16 weeks. The presence of
      heartburn, regurgitation, abnormal levels of esophageal acid, or nonacid reflux
      did not predict response to therapy.

PMID- 20801119
TI  - Helicobacter pylori infection promotes methylation and silencing of trefoil
      factor 2, leading to gastric tumor development in mice and humans.
AB  - BACKGROUND & AIMS: Trefoil factors (TFFs) regulate mucosal repair and suppress
      tumor formation in the stomach. Tff1 deficiency results in gastric cancer,
      whereas Tff2 deficiency increases gastric inflammation. TFF2 expression is
      frequently lost in gastric neoplasms, but the nature of the silencing mechanism
      and associated impact on tumorigenesis have not been determined. METHODS: We
      investigated the epigenetic silencing of TFF2 in gastric biopsy specimens from
      individuals with Helicobacter pylori-positive gastritis, intestinal metaplasia,
      gastric cancer, and disease-free controls. TFF2 function and methylation were
      manipulated in gastric cancer cell lines. The effects of Tff2 deficiency on tumor
      growth were investigated in the gp130(F/F) mouse model of gastric cancer.
      RESULTS: In human tissue samples, DNA methylation at the TFF2 promoter began at
      the time of H pylori infection and increased throughout gastric tumor
      progression. TFF2 methylation levels were inversely correlated with TFF2
      messenger RNA levels and could be used to discriminate between disease-free
      controls, H pylori-infected, and tumor tissues. Genome demethylation restored
      TFF2 expression in gastric cancer cell lines, so TFF2 silencing requires
      methylation. In Tff2-deficient gp130(F/F)/Tff2(-/-) mice, proliferation of
      mucosal cells and release of T helper cell type-1 (Th-1) 1 cytokines increased,
      whereas expression of gastric tumor suppressor genes and Th-2 cytokines were
      reduced, compared with gp130(F/F)controls. The fundus of gp130(F/F)/Tff2(-/-)
      mice displayed glandular atrophy and metaplasia, indicating accelerated
      preneoplasia. Experimental H pylori infection in wild-type mice reduced antral
      expression of Tff2 by increased promoter methylation. CONCLUSIONS: TFF2
      negatively regulates preneoplastic progression and subsequent tumor development
      in the stomach, a role that is subverted by promoter methylation during H pylori
      infection.

PMID- 20801121
TI  - NOTCH1 and NOTCH3 coordinate esophageal squamous differentiation through a CSL
      dependent transcriptional network.
AB  - BACKGROUND & AIMS: The Notch receptor family regulates cell fate through cell
      cell communication. CSL (CBF-1/RBP-jkappa, Su(H), Lag-1) drives canonical Notch
      mediated gene transcription during cell lineage specification, differentiation,
      and proliferation in the hematopoietic system, the intestine, the pancreas, and
      the skin. However, the functional roles of Notch in esophageal squamous
      epithelial biology are unknown. METHODS: Normal esophageal keratinocytes were
      stimulated with calcium chloride to induce terminal differentiation. The squamous
      epithelia were reconstituted in organotypic 3-dimensional culture, a form of
      human tissue engineering. Notch was inhibited in culture with a gamma-secretase
      inhibitor or dominant negative mastermind-like 1 (DNMAML1). The roles of Notch
      receptors were evaluated by in vitro gain-of-function and loss-of-function
      experiments. Additionally, DNMAML1 was targeted to the mouse esophagus by
      cytokeratin K14 promoter-driven Cre (K14Cre) recombination of Lox-STOP-Lox
      DNMAML1. Notch-regulated gene expression was determined by reporter transfection,
      chromatin immunoprecipitation assays, quantitative reverse-transcription
      polymerase chain reaction, Western blotting, immunofluorescence, and
      immunohistochemistry. RESULTS: NOTCH1 (N1) was activated at the onset of squamous
      differentiation in the esophagus. Intracellular domain of N1 (ICN1) directly
      activated NOTCH3 (N3) transcription, inducing HES5 and early differentiation
      markers such as involucrin (IVL) and cytokeratin CK13 in a CSL-dependent fashion.
      N3 enhanced ICN1 activity and was required for squamous differentiation. Loss of
      Notch signaling in K14Cre;DNMAML1 mice perturbed esophageal squamous
      differentiation and resulted in N3 loss and basal cell hyperplasia. CONCLUSIONS:
      Notch signaling is important for esophageal epithelial homeostasis. In
      particular, the cross talk of N3 with N1 during differentiation provides novel,
      mechanistic insights into Notch signaling and squamous epithelial biology.

PMID- 20801122
TI  - Linaclotide improves abdominal pain and bowel habits in a phase IIb study of
      patients with irritable bowel syndrome with constipation.
AB  - BACKGROUND & AIMS: Linaclotide, a minimally absorbed, 14-amino acid peptide
      agonist of guanylate cyclase-C, has shown benefit in a proof-of-concept study for
      the treatment of patients with irritable bowel syndrome (IBS) with constipation
      (IBS-C). We assessed the efficacy and safety of linaclotide at a daily dose range
      of 75-600 MUg in IBS-C. METHODS: We performed a randomized, double-blind,
      multicenter, placebo-controlled study of 420 patients with IBS-C given oral
      linaclotide at doses of 75, 150, 300, or 600 MUg or placebo once daily for 12
      weeks. End points included change from baseline in daily bowel habits, daily
      abdominal symptoms, and weekly global assessments, in addition to responder
      criteria. RESULTS: All doses of linaclotide significantly improved bowel habits,
      including frequency of spontaneous bowel movements and complete spontaneous bowel
      movements (primary end point), severity of straining, and stool consistency.
      Abdominal pain was significantly reduced from baseline, compared with placebo;
      mean changes in abdominal pain (assessed on a 5-point scale) from baseline were 
      0.71, -0.71, -0.90, and -0.86 for linaclotide doses of 75, 150, 300, and 600 MUg,
      respectively, compared with -0.49 for placebo. Likewise, most doses of
      linaclotide significantly improved other abdominal symptoms, including discomfort
      and bloating, and global measures of IBS-C compared with placebo. Effects were
      observed within the first week and were sustained throughout 12 weeks of
      treatment. Except for diarrhea, the incidence of adverse events was similar
      between placebo and linaclotide groups. CONCLUSIONS: Linaclotide, across a wide
      range of doses, significantly improved symptoms of IBS-C, including abdominal
      pain and bowel symptoms. Diarrhea was the only dose-dependent adverse event and
      was usually of mild or moderate severity.

PMID- 20801123
TI  - Long-term therapy with tenofovir is effective for patients co-infected with human
      immunodeficiency virus and hepatitis B virus.
AB  - BACKGROUND & AIMS: We investigated the long-term efficacy and renal safety of
      tenofovir disoproxil fumarate (TDF), administered to patients co-infected with
      human immunodeficiency virus and hepatitis B virus (HBV) as part of an
      antiretroviral therapy. METHODS: We performed a multicenter, prospective cohort
      study of 102 patients co-infected with human immunodeficiency virus and HBV who
      were treated with TDF. RESULTS: At baseline, 80% of patients had a detectable
      viral load (HBV DNA >20 IU/mL). Among patients positive for hepatitis B e antigen
      (HBeAg) (n = 67), 92% had a virologic response (HBV DNA <20 IU/mL) after 5 years
      of treatment. There was no difference between patients with or without lamivudine
      resistance at baseline (P = .39). Loss rates of HBeAg and hepatitis B s antigen
      (HBsAg) were 46% and 12%, respectively. Among HBeAg-negative patients (n = 15),
      100% had a virologic response after 4 years of treatment and 2 (13%) lost HBsAg.
      Twenty subjects (20%, all HBeAg-negative) had undetectable HBV DNA at baseline;
      during a median follow-up period of 52 months (interquartile range, 41-63 mo), 19
      (95%) maintained a virologic response and 2 (10%) lost HBsAg. Overall, one
      patient acquired a combination of resistance mutations for anti-HBV drugs and
      experienced a virologic breakthrough. Three (3%) patients discontinued TDF
      because of increased serum creatinine levels. The estimated decrease in renal
      function after 5 years of TDF therapy was 9.8 mL/min/1.73 m(2), which was most
      pronounced shortly after TDF therapy was initiated. CONCLUSIONS: TDF,
      administered as part of antiretroviral therapy, is a potent anti-HBV agent with a
      good resistance profile throughout 5 years of therapy. Only small nonprogressive
      decreases in renal function were observed.

PMID- 20801125
TI  - Development of a second generation anti-Mullerian hormone (AMH) ELISA.
AB  - AMH is a glycoprotein dimer composed of two 72kDa monomers linked by disulfide
      bridges. It belongs to the transforming growth factor-beta family. AMH performs
      various physiological functions. In males, AMH is secreted by the Sertoli cells
      of the testis. During embryonic development, AMH is responsible for Mullerian
      duct regression. AMH continues to be produced by the testicles until puberty and
      then decreases slowly to residual post-puberty values. In females, AMH is
      produced in small amounts by ovarian granulosa cells after birth, until
      menopause, and then becomes undetectable. A two-step, sandwich-type enzymatic
      microplate assay has been developed to measure AMH levels in 20 MUL of sample in
      less than 3h. AMH calibrators range from 0.2 to 28 ng/mL. The antibodies used in
      the assay bind to the mature region of AMH, which is more stable to proteolysis
      compared to prohormone region. The AMH Gen II assay (Beckman Coulter, Inc.,
      Webster, Texas) was standardized to the Immunotech (IOT, Beckman Coulter, Inc.,
      Marseilles, France) AMH assay. AMH Gen II, when compared to IOT using 120 serum
      samples in the range of 0-20.4 ng/mL yielded a correlation coefficient of 0.98
      and a slope of 1.0. Total imprecision, calculated on four samples over 40 runs,
      four replicates per run, between two lots using CLSI EP5-A guidelines, was 5.7%
      at 3.8 ng/mL, 7.7% at 4.4 ng/mL, 5.8% at 14 ng/mL and 5.3% at 16.4 ng/mL. The
      average analytical sensitivity calculated by the interpolation of the mean plus
      two standard deviations of 16 replicates of the zero calibrator on two
      independent lots was 0.08ng/mL. Dilution and spiking studies showed an average
      recovery of 91-110%. Lot-to-lot comparison of two independent lots testing 38
      serum samples (1.5-33 ng/mL range) yielded a slope of 1.01, intercept of -0.08
      ng/mL and r of 0.99. When potential interferents (hemoglobin, triglycerides, and
      bilirubin) were added at two times the physiological concentrations, AMH
      concentrations were within +/- 10% of the control. A highly specific and
      reproducible microplate AMH Gen II assay has been developed to standardize the
      measurement of AMH between methods. The performance of the AMH Gen II assay is
      ideal for investigation into the physiologic roles of AMH in men and women.

PMID- 20801124
TI  - Hepatoblast-like progenitor cells derived from embryonic stem cells can
      repopulate livers of mice.
AB  - BACKGROUND & AIMS: Hepatocyte-like cells can be derived from pluripotent stem
      cells such as embryonic stem (ES) cells, but ES cell-derived hepatic cells with
      extensive capacity to repopulate liver have not been identified. We aimed to
      identify and purify ES cell-derived hepatoblast-like progenitor cells and to
      explore their capacity for liver repopulation in mice after in vitro expansion.
      METHODS: Unmanipulated mouse ES cells were cultured under defined conditions and
      allowed to undergo stepwise hepatic differentiation. The derived hepatic cells
      were examined by morphologic, fluorescence-activated cell sorting, gene
      expression, and clonal expansion analyses. The capacities of ES cell-derived
      hepatic progenitor cells to repopulate liver were investigated in mice that were
      deficient in fumarylacetoacetate hydrolase (Fah) (a model of liver injury).
      RESULTS: Mouse ES cells were induced to differentiate into a population that
      contained hepatic progenitor cells; this population included cells that expressed
      epithelial cell adhesion molecule (EpCAM) but did not express c-Kit. Clonal
      hepatic progenitors that arose from single c-Kit(-)EpCAM(+) cells could undergo
      long-term expansion and maintain hepatoblast-like characteristics. Enriched c
      Kit(-)EpCAM(+) cells and clonally expanded hepatic progenitor cells repopulated
      the livers of Fah-deficient mice without inducing tumorigenesis. CONCLUSIONS: ES
      cell-derived c-Kit(-)EpCAM(+) cells contain a population of hepatoblast-like
      progenitor cells that can repopulate livers of mice.

PMID- 20801126
TI  - Effects of wing polyphenism, aphid genotype and host plant chemistry on energy
      metabolism of the grain aphid, Sitobion avenae.
AB  - Wing dimorphism has been proposed as a strategy to face trade-offs between flight
      capability and fecundity. In aphids, individuals with functional wings have
      slower development and lower fecundity compared with wingless individuals.
      However, differential maintenance costs between winged and wingless aphids have
      not been deeply investigated. In the current study, we studied the combined
      effect of wing dimorphism with the effects of aphid genotypes and of wheat hosts
      having different levels of chemical defences (hydroxamic acids, Hx) on adult body
      mass and standard metabolic rates (SMR) of winged and wingless morphs of the
      grain aphid, Sitobion avenae. We found that wingless aphids had higher body mass
      than winged aphids and that body mass also increased towards host with high Hx
      levels. Furthermore, winged aphids showed a plastic SMR in terms of Hx levels,
      whereas wingless aphids displayed a rigid reaction norm (significant interaction
      between morph condition and wheat host). These findings suggest that winged
      aphids have reduced adult size compared to wingless aphids, likely due to costs
      associated to the development of flight structure in early-life stages. These
      costs contrast with the absence of detectable metabolic costs related to fuelling
      and maintenance of the flight apparatus in adults.

PMID- 20801127
TI  - Paclitaxel accelerates spontaneous calcium oscillations in cardiomyocytes by
      interacting with NCS-1 and the InsP3R.
AB  - Paclitaxel (Taxol) is a microtubule-stabilizing compound that is used for cancer
      chemotherapy. However, Taxol administration is limited by serious side effects
      including cardiac arrhythmia, which cannot be explained by its microtubule
      stabilizing effect. Recently, neuronal calcium sensor 1 (NCS-1), a calcium
      binding protein that modulates the inositol-1,4,5-trisphosphate receptor
      (InsP(3)R), was described as a binding partner of Taxol and as a substrate of
      calpain. We examined calcium signaling processes in cardiomyocytes after
      treatment with Taxol to investigate the basis of Taxol-induced cardiac
      arrhythmia. After treating isolated neonatal rat ventricular myocytes with a
      therapeutic concentration of Taxol for several hours live cell imaging
      experiments showed that the frequency of spontaneous calcium oscillations
      significantly increased. This effect was not mimicked by other tubulin
      stabilizing agents. However, it was prevented by inhibiting the InsP(3)R. Taxol
      treated cells had increased expression of NCS-1, an effect also detectable after
      Taxol administration in vivo. Short hairpin RNA mediated knockdown of NCS-1
      decreased InsP(3)R dependent intracellular calcium release, whereas Taxol
      treatment, that increased NCS-1 levels, increased InsP(3)R dependent calcium
      release. The effects of Taxol were ryanodine receptor independent. At the single
      channel level Taxol and NCS-1 mediated an increase in InsP(3)R activity. Calpain
      activity was not affected by Taxol in cardiomyocytes suggesting a calpain
      independent signaling pathway. In short, our study shows that Taxol impacts
      calcium signaling and calcium oscillations in cardiomyocytes through NCS-1 and
      the InsP(3)R.

PMID- 20801128
TI  - VAMP-1, VAMP-2, and syntaxin-4 regulate ANP release from cardiac myocytes.
AB  - ANP is a peptide released by cardiac myocytes that regulates blood pressure and
      natriuresis. However, the molecular mechanisms controlling ANP release from
      cardiac myocytes are not defined. We now identify three components of the
      exocytic machinery that regulate ANP release from atrial myocytes. We found that
      cardiac myocytes express N-ethylmaleimide sensitive factor (NSF), soluble NSF
      attachment protein (alpha-SNAP), and SNAP receptors (SNAREs). Additionally we
      found that specific SNARE molecules, VAMP-1 and VAMP-2, both co-sediment and co
      localize with ANP. Also, one SNARE molecule, syntaxin-4, partially co-sediments
      and partially co-localizes with ANP. Furthermore, these three SNAREs, syntaxin-4
      and VAMP-1 and VAMP-2, form a SNARE complex inside cardiac myocytes. Finally,
      knockdown of VAMP-1, VAMP-2, or syntaxin-4 blocks regulated release of ANP. In
      contrast, silencing of VAMP-3 did not have an effect on ANP release. Our data
      suggest that three specific SNAREs regulate cardiac myocyte exocytosis of ANP.
      Pathways that modify the exocytic machinery may influence natriuresis and blood
      pressure.

PMID- 20801129
TI  - Survivin: a novel player in insulin cardioprotection against myocardial
      ischemia/reperfusion injury.
AB  - Insulin inhibits ischemia/reperfusion-induced myocardial apoptosis through the
      activation of a survival signaling cascade including the phosphatidylinositol 3
      kinase (PI3K)-Akt pathway. However, the down-stream mechanism of PI3K remains
      elusive. This study is aimed at investigating whether survivin (SVV) plays a role
      in the insulin-induced anti-apoptotic effect in the ischemic/reperfused (I/R)
      hearts, and if so, further determining the signaling mechanism involved. Isolated
      adult rat hearts were subjected to 30 min regional ischemia followed by
      reperfusion with or without insulin (10(-7)mol/L) at the onset of reperfusion.
      Reperfusion with insulin inhibited myocardial apoptosis and reduced infarct size,
      along with significantly up-regulated myocardial SVV expression (5.9+/-0.3 Group
      MI/R+Ins vs. 2.1+/-0.1 Group MI/R, p<0.05) and increased phosphorylations of mTOR
      and p70S6K compared with I/R group, which was blocked by pretreatment of PI3K
      inhibitor LY294002. Rapamycin, a specific mTOR inhibitor, did not alter insulin
      induced Akt phosphorylation but significantly inhibited SVV expression (from
      6.1+/-0.3 to 3.0+/-0.15, p<0.05). Moreover, rapamycin blunted insulin-induced
      anti-apoptosis in the I/R hearts (8.1+/-0.4% vs. 16.5+/-1.8%, p<0.05). To further
      ascertain the role of SVV in insulin-induced cardioprotection, cardiomyocytes
      were transfected with adenovirus encoding SVV (gain-of-function) or siRNA
      targeting SVV (loss-of-function). Overexpression of SVV decreased I/R-induced
      cardiomyocyte apoptosis in vitro, while siRNA targeting SVV significantly blunted
      the anti-apoptotic effect of insulin. Taken together, these results suggest a
      novel role of PI3K/Akt/mTOR/SVV signaling in the cardioprotective effect of
      insulin.

PMID- 20801131
TI  - How different two almost identical action potentials can be: a model study on
      cardiac repolarization.
AB  - Spatial heterogeneity in the properties of ion channels generates spatial
      dispersion of ventricular repolarization, which is modulated by gap junctional
      coupling. However, it is possible to simulate conditions in which local
      differences in excitation properties are electrophysiologically silent and only
      play a role in pathological states. We use a numerical procedure on the Luo-Rudy
      phase 1 model of the ventricular action potential (AP1) in order to find a
      modified set of model parameters which generates an action potential profile
      (AP2) almost identical to AP1. We show that, although the two waveforms elicited
      from resting conditions as a single AP are very similar and belong to membranes
      sharing similar passive electrical properties, the modified membrane generating
      AP2 is a weaker current source than the one generating AP1, has different
      sensitivity to up/down-regulation of ion channels and to extracellular potassium,
      and a different electrical restitution profile. We study electrotonic interaction
      of AP1- and AP2- type membranes in cell pairs and in cable conduction, and find
      differences in source-sink properties which are masked in physiological
      conditions and become manifest during intercellular uncoupling or partial block
      of ion channels, leading to unidirectional block and spatial repolarization
      gradients. We provide contour plot representations that summarize differences and
      similarities. The present report characterizes an inverse problem in cardiac
      cells, and strengthen the recently emergent notion that a comprehensive
      characterization and validation of cell models and their components are necessary
      in order to correctly understand simulation results at higher levels of
      complexity.

PMID- 20801132
TI  - Impact of group mixing on disease dynamics.
AB  - A general mathematical model is proposed to study the impact of group mixing in a
      heterogeneous host population on the spread of a disease that confers temporary
      immunity upon recovery. The model contains general distribution functions that
      account for the probabilities that individuals remain in the recovered class
      after recovery. For this model, the basic reproduction number R0 is identified.
      It is shown that if R0 < 1, then the disease dies out in the sense that the
      disease free equilibrium is globally asymptotically stable; whereas if R0 > 1,
      this equilibrium becomes unstable. In this latter case, depending on the
      distribution functions and the group mixing strengths, the disease either
      persists at a constant endemic level or exhibits sustained oscillatory behavior.

PMID- 20801130
TI  - A structural and functional perspective into the mechanism of Ca2+-sensitizers
      that target the cardiac troponin complex.
AB  - The Ca(2+) dependent interaction between troponin I (cTnI) and troponin C (cTnC)
      triggers contraction in heart muscle. Heart failure is characterized by a
      decrease in cardiac output, and compounds that increase the sensitivity of
      cardiac muscle to Ca(2+) have therapeutic potential. The Ca(2+)-sensitizer,
      levosimendan, targets cTnC; however, detailed understanding of its mechanism has
      been obscured by its instability. In order to understand how this class of
      positive inotropes function, we investigated the mode of action of two fluorine
      containing novel analogs of levosimendan; 2',4'-difluoro(1,1'-biphenyl)-4-yloxy
      acetic acid (dfbp-o) and 2',4'-difluoro(1,1'-biphenyl)-4-yl acetic acid (dfbp).
      The affinities of dfbp and dfbp-o for the regulatory domain of cTnC were measured
      in the absence and presence of cTnI by NMR spectroscopy, and dfbp-o was found to
      bind more strongly than dfbp. Dfbp-o also increased the affinity of cTnI for
      cTnC. Dfbp-o increased the Ca(2+)-sensitivity of demembranated cardiac trabeculae
      in a manner similar to levosimendan. The high resolution NMR solution structure
      of the cTnC-cTnI-dfbp-o ternary complex showed that dfbp-o bound at the
      hydrophobic interface formed by cTnC and cTnI making critical interactions with
      residues such as Arg147 of cTnI. In the absence of cTnI, docking localized dfbp-o
      to the same position in the hydrophobic groove of cTnC. The structural and
      functional data reveal that the levosimendan class of Ca(2+)-sensitizers work by
      binding to the regulatory domain of cTnC and stabilizing the pivotal cTnC-cTnI
      regulatory unit via a network of hydrophobic and electrostatic interactions, in
      contrast to the destabilizing effects of antagonists such as W7 at the same
      interface.

PMID- 20801133
TI  - On the number of recovered individuals in the SIS and SIR stochastic epidemic
      models.
AB  - The basic models of infectious disease dynamics (the SIS and SIR models) are
      considered. Particular attention is paid to the number of infected individuals
      that recovered and its relationship with the final epidemic size. We investigate
      this descriptor both until the extinction of the epidemic and in transient
      regime. Simple and efficient methods to obtain the distribution of the number of
      recovered individuals and its moments are proposed and discussed with respect to
      the previous work. The methodology could also be extended to other stochastic
      epidemic models. The theory is illustrated by numerical experiments, which
      demonstrate that the proposed computational methods can be applied efficiently.
      In particular, we use the distribution of the number of individuals removed in
      the SIR model in conjunction with data of outbreaks of ESBL observed in the
      intensive care unit of a Spanish hospital.

PMID- 20801134
TI  - Right fronto-parietal dysfunction in children with ADHD and developmental
      dyslexia as determined by line bisection judgements.
AB  - Visual line bisection is a reliable and valid laterality task that is typically
      used with patients with acquired brain damage to assess right hemisphere
      functioning. Neurologically normal individuals tend to bisect lines to the left
      of the objective midline whereas those with right parietal damage bisect lines to
      the right. In this study children with ADHD were matched with children with
      developmental dyslexia on IQ and gender to test the hypothesis that right
      hemisphere neurological abnormalities underlie the behavioural deficits observed
      in these two disorders. Line bisection performance was compared between groups as
      a function of response hand, scanning direction and line position. In contrast to
      results typically found with neurologically normal children, a rightward bias was
      found for both clinical groups, but to different degrees depending on which hand
      was used to bisect lines. These findings suggest pathology of the corpus callosum
      and/or the right fronto-parietal cortex.

PMID- 20801135
TI  - The emotional paradox: dissociation between explicit and implicit processing of
      emotional prosody in schizophrenia.
AB  - People with schizophrenia show well-replicated deficits on tasks of explicit
      recognition of emotional prosody. However it remains unclear whether they are
      still sensitive to the implicit cues of emotional prosody, particularly when they
      exhibit high levels of social anhedonia. A dual processing model suggesting a
      dissociation between the neural networks involved in explicit and implicit
      recognition of emotional prosody has yet to be validated. 21 participants with
      schizophrenia and 21 controls were recruited. In the explicit recognition task,
      individuals listened to semantically neutral words pronounced with two different
      emotions and judged their emotional prosody. In the vocal emotional Stroop task,
      patients and controls listened to words with a positive or negative emotional
      valence pronounced with congruent or incongruent emotional prosody and judged
      their emotional content. Patients were also assessed with the Chapman Anhedonia
      Questionnaire and the Schizophrenic Communication Disorders scale. Individuals
      with schizophrenia were impaired in their explicit recognition of emotional
      prosody related to controls. In contrast, they showed a vocal emotional Stroop
      effect that was identical to controls for reaction time and greater for accuracy:
      patients were still sensitive to implicit emotional prosody. In addition the
      vocal emotional Stroop score increased with social anhedonia but was unrelated to
      communication disorders. Whereas explicit vocal affect recognition is impaired,
      implicit processing of emotional prosody seems to be preserved in schizophrenia.
      Our results provide evidence that at a behavioural level, the implicit and
      explicit processing of emotional prosody can be dissociated. Remediation of
      emotional prosody recognition in schizophrenia should target cognitive rather
      than sensory processes.

PMID- 20801136
TI  - Increased attentional demands impair contralesional space awareness following
      stroke.
AB  - Rate and severity of contralesional loss of awareness following stroke is highly
      variable across patients and assessment methods. We studied whether the degree of
      impairment for contralesional space awareness depends on the quantity of
      attentional resources that are available for task performance. A new computer
      based paradigm was used to assess visual extinction and single-target detection
      rate in four right hemisphere stroke patients. In the single-task condition, they
      had to report only the position of the target(s) ("right", "left", or "both"
      sides). In the dual-task conditions, patients also performed a second task,
      visual or auditory, that recruited additional attentional resources. The same
      tasks were also performed by healthy controls and by a left hemisphere stroke
      patient. Patients' performance was apparently unimpaired in the single-task
      condition. In contrast, dramatic failures to report the left-sided target emerged
      in the dual-task conditions. The performance of control participants was
      unaffected by the dual-task manipulation, whereas the left stroke patient showed
      the opposite pattern (i.e., unawareness of right-sided targets). Severe
      contralesional space unawareness under dual-task conditions reveals that
      visuospatial deficits can dramatically emerge when attentional resources are
      consumed by a concurrent task. Apparently spared contralesional awareness may
      simply reflect the availability of resources that are just sufficient to perform
      a single-task. This finding has important implications for the assessment of
      contralesional space awareness following stroke, because everyday life activities
      are often more demanding than most of the tests adopted for diagnosing space
      awareness disorders.

PMID- 20801137
TI  - Obesity-resistant S5B rats showed greater cocaine conditioned place preference
      than the obesity-prone OM rats.
AB  - BACKGROUND: Dopamine (DA) and the DA D2 receptor (D2R) are involved in the
      rewarding and conditioned responses to food and drug rewards. Osborne-Mendel (OM)
      rats are genetically prone and S5B/P rats are genetically resistant to obesity
      when fed a high-fat diet. We hypothesized that the differential sensitivity of
      these two rat strains to natural rewards may also be reflected in sensitivity to
      drugs of abuse. Therefore, we tested whether OM and S5B/P rats showed a
      differential preference to cocaine using conditioned place preference (CPP). To
      also evaluate whether there is specific involvement of the D2R in this
      differential conditioning sensitivity, we then tested whether the D2R agonist
      bromocriptine (BC) would differentially affect the effects of cocaine in the two
      strains. METHODS: OM and S5B/P rats were conditioned with cocaine (5 or 10mg/kg)
      in one chamber and saline in another for 8days. Rats were then tested for cocaine
      preference. The effects of BC (0.5, 1, 5, 10, 20mg/kg) on cocaine preference were
      then assessed in subsequent test sessions. RESULTS: OM rats did not show a
      significant preference for the cocaine-paired chamber on test day. Only the S5B/P
      rats showed cocaine CPP. Later treatment with only the highest dose of BC
      resulted in reduced cocaine CPP in S5B/P rats when treated with 5mg/kg cocaine
      and in OM rats treated with 10mg/kg cocaine. CONCLUSION: Our results indicated
      that obesity-resistant S5B rats showed greater cocaine CPP than the obesity-prone
      OM rats. These findings do not support a theory of common vulnerability for
      reinforcer preferences (food and cocaine). However, they show that BC reduced
      cocaine conditioning effects supporting at least a partial regulatory role of D2R
      in conditioned responses to drugs.

PMID- 20801138
TI  - Microbial transformation of 3beta-acetoxypregna-5,16-diene-20-one by Penicillium
      citrinum.
AB  - The biotransformation of 3beta-acetoxypregna-5,16-diene-20-one (1) by using a
      filamentous fungus Penicillium citrinum resulted in the production of four
      metabolites 2-5. The structures of these compounds were elucidated by different
      spectroscopic analysis (1D- and 2D-NMR) and HR-ESI-MS as 3beta,7beta-dihydroxy
      pregn-5,16(17)-dien-20-one (2), 3beta-hydroxy-7alpha-methoxy-pregn-5,16(17)-dien
      20-one (3), 3beta,7beta,11alpha-trihydroxy-pregn-5,16(17)-dien-20-one (4), and a
      known 3beta,7alpha-dihydroxy-pregn-5,16(17)-dien-20-one (5). The 7-O-methylation
      is a novel reaction in the field of microbial transformation of pregnane
      steroids.

PMID- 20801139
TI  - Beneficial effect of 17beta-estradiol on hyperglycemia and islet beta-cell
      functions in a streptozotocin-induced diabetic rat model.
AB  - The modulating effect of estrogen on glucose homeostasis remains a controversial
      issue at present. In this study, we sought to determine the beneficial effect of
      17beta-estradiol (E2) on hyperglycemia and islet beta-cell functions in
      streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were
      injected i.p. with STZ to induce a relatively mild diabetic condition. The rats
      were then treated with E2 orally at 500 MUg/kg body weight/day for 15 days to
      evaluate the modulating effect on hyperglycemia, insulin secretion, and islet
      beta-cell proliferation. E2 administration for 10 days significantly lowered
      plasma glucose levels, increased plasma insulin levels, and improved glucose
      tolerance by attenuating insulin response to oral glucose loading. These
      beneficial effects of E2 were accompanied by increases in islet number and
      volume, rate of islet cell proliferation, and the amount of insulin secreted. The
      growth-stimulatory effect of E2 on islet cells was linked to the functions of the
      estrogen receptor alpha. Notably, these protective effects of E2 on diabetic
      conditions were basically not observed when the STZ-treated rats had a more
      severe degree of islet damage and hyperglycemia. Taken together, we conclude that
      E2 can promote the regeneration of damaged pancreatic islets by stimulating beta
      cell proliferation in diabetic rats, and this effect is accompanied by
      improvements in glucose tolerance and a decrease in plasma glucose levels. These
      findings suggest that oral administration of E2 may be beneficial in diabetic
      patients with an accelerated loss of islet beta-cells.

PMID- 20801140
TI  - The perceptual expansion of a filled area depends on textural characteristics.
AB  - According to the Oppel-Kundt illusion, a filled space appears larger than an
      empty one. In the present research we studied how textural characteristics affect
      the perceived size of two-dimensional patterns. We investigated the perceived
      extension of square textures by manipulating spatial frequency and filling
      microelements' numerosity. Subjects compared the test stimuli with a uniform gray
      square varied in size and performed the task both with the adjustment and the
      constant stimuli methods. An illusory increment of area extension was generally
      found with textured stimuli. The illusory effect increased with spatial frequency
      and decreased with the microelements' number, indicating an independent
      processing of these two basic properties. Moreover, the smaller effect found when
      spatial frequency extraction became harder, confirmed that the illusion involves
      spatial frequency processing. Finally, the reduced overestimation of areas
      observed with a weaker subparts' articulation confirmed the relevance of clear
      distinguishable micropatterns at the basis of the phenomenon. Those results
      demonstrate the influence of textural statistical properties on perceiving the
      size of a visual object.

PMID- 20801141
TI  - A computational vector-map model of neonate saccades: modulating the externality
      effect through refraction periods.
AB  - The present study develops an explicit and predictive computational model of
      neonate saccades based on the interaction of several simple mechanisms, including
      the tendency to fixate towards areas of high contrast, and the decay and recovery
      of a world-centered contrast representation simulating a low-level inhibition of
      return mechanism. Emergent properties similar to early visual behaviors develop,
      including the externality effect (or tendency to focus on external then internal
      features). The age-associated progression of this effect is modulated by the
      decay period of the model's contrast representation, where the high-level
      behavior of either scanning broadly or locally is modulated by a single decay
      parameter.

PMID- 20801142
TI  - Plasticity of TRPM1 expression and localization in the wild type and degenerating
      mouse retina.
AB  - The light response in retinal ON bipolar cells is associated with disinhibition
      of current flow through cation channels recently identified as type 1 members of
      the melastatin transient receptor potential (TRPM) family. We determined the
      developmental expression of Trpm1 in the wild type C57BL/6, DBA/2J, DBA2J-Gpnmb
      mouse retinas and in Pde6brd1 retinas characterized by degeneration of rod
      photoreceptors. Trpm1 mRNA in wild type retinas was low at birth but exhibited
      progressive increases in abundance up to early adulthood at postnatal day 21
      (P21). Retinal Trpm1 mRNA content did not decrease following loss of
      photoreceptors. At P21, TRPM1-immunopositive perikarya migrated into the outer
      nuclear layer. The TRPM1 protein was trafficked to discrete postsynaptic puncta
      in wild type retinas whereas in adult Pde6brd1 mouse retinas, TRPM1 translocated
      to bipolar perikarya and bar-like structures in the distal inner nuclear layer.
      These findings show that expression and localization of the TRPM1 in the mouse
      retina is plastic, modulated by use-dependence and availability of sustained
      excitatory input.

PMID- 20801143
TI  - The disembodied eye: consequences of displacing perception from action.
AB  - In our research, people use actions to expose hidden targets as planar images
      displayed either in situ or ex situ (displaced remotely). We show that because ex
      situ viewing impedes relating actions to their perceptual consequences, it
      impairs localizing targets, including compensating for surface deformation, and
      directing movement toward them. Using a 3D analogue of anorthoscopic perception,
      we demonstrate that spatio-temporal integration of contiguous planar slices is
      possible when action and perception are co-located, but not when they are
      separated. Ex situ viewing precludes the formation of a spatial frame of
      reference that supports complex visualization from action.

PMID- 20801144
TI  - Identifying steep psychometric function slope quickly in clinical applications.
AB  - Knowledge of an observer's psychometric function slope is potentially useful in
      clinical visual psychophysics (for example, perimetry), however, the short test
      times necessary in a clinical setting typically prevent slope estimation. We
      explore, using computer simulation, the performance of several possible
      procedures for estimating psychometric function slope within limited
      presentations (aiming for approximately 30 or 140 trials). Procedures were based
      on either adaptive staircase or Bayesian techniques, and performance was compared
      to a Method of Constant Stimuli. An adaptation of the Psi algorithm was best
      performing, being able to reliably identify steep from flat psychometric
      functions in less than 30 presentations, however reliable quantification of
      shallow psychometric functions was not possible.

PMID- 20801145
TI  - Mouse models of dominant optic atrophy: what do they tell us about the
      pathophysiology of visual loss?
AB  - Dominant optic atrophy (DOA) is the most common inherited optic neuropathy
      affecting one in every 12,000 people. It presents with bilateral visual loss,
      central visual fields defects, colour vision disturbance and optic disc pallor.
      OPA1 has been identified as the responsible gene and its locus mapped to
      chromosome 3q28-q29. Mutations in this gene are responsible for the clinical
      phenotype in over 70% of patients with DOA. Histopathological studies in tissues
      from patients reveal loss of retinal ganglion cells but the paucity of viable
      human tissue has raised the importance of an animal model to study the
      pathophysiology of the disease. In the last decade considerable work has gone
      into the generation of animal, most notably mouse, models of Opa1 DOA. Two murine
      models of DOA have been published, designated B6;C3-Opa1(Q285STOP) and B6;C3
      Opa1(329-355del) and they provide valuable insights with respect to neurological
      and visual phenotyping, mitochondrial dysfunction, optic nerve and axonal
      changes, retinal ganglion cell depletion and dendritic atrophy. Here we summarise
      the current state of knowledge of the mechanisms of disease based on data from
      these models of Opa1 DOA.

PMID- 20801146
TI  - Association of visual function and ganglion cell layer thickness in patients with
      diabetes mellitus type 1 and no or minimal diabetic retinopathy.
AB  - Diabetic retinopathy (DR) classically presents with micro-aneurysms, small
      haemorrhages and/or lipoprotein exudates. Several studies have indicated that
      neural loss occurs in DR even before vascular damage can be observed. This study
      evaluated the possible relationship between structure (spectral domain-optical
      coherence tomography) and function (Rarebit visual field test) in patients with
      type 1 diabetes mellitus and no or minimal diabetic retinopathy (DR). Results
      demonstrated loss of macular visual function and corresponding thinning of the
      ganglion cell layer (GCL) in the pericentral area of the macula of diabetic
      patients (Rs = 0.65, p < 0.001). In multivariable logistic regression analysis,
      GCL thickness remained an independent predictor of decreased visual function (OR
      1.5, 95% CI 1.1-2.1). Early DR seems to include a neurodegenerative component.

PMID- 20801147
TI  - Efficient coding and multiple motions.
AB  - Based on the principle of efficient coding, we present a theoretical framework
      for how to categorize the basic types of changes that can occur in a spatio
      temporal signal. First, theoretical results for the problem of estimating
      multiple transparent motions are reviewed. Then, confidence measures for the
      presence of multiple motions are used to derive a basic alphabet of local signal
      variation that includes motion layers. To better understand and visualize this
      alphabet, a representation of motions in the projective plane is used. A further,
      practical contribution is an interactive tool that allows generating multiple
      motion patterns and displaying them in various apertures. In our framework, we
      can explain some well-known results on coherent motion and a few more complex
      perceptual phenomena such as the 2D-1D entrainment effect, but the focus of this
      paper is on the methods. Our working hypothesis is that efficient representations
      can be obtained by suppressing all the redundancies that arise if the visual
      input does not change in a particular direction, or a set of directions. Finally,
      we assume that human eye movements will tend to avoid the redundant parts of the
      visual input and report results where our framework has been used to obtain very
      good predictions of eye movements made on overlaid natural videos.

PMID- 20801148
TI  - Review of the major findings about Duane retraction syndrome (DRS) leading to an
      updated form of classification.
AB  - In view of all the reported evidence by electromyography in the 1970s, by
      histology in the 1980s, and by cerebral imagery since the 2000s, Duane retraction
      syndrome (DRS) has been described as the consequence of a congenital anomaly of
      the 6th cranial nerve nuclei with aberrant innervations by supply from the 3rd
      cranial nerve. Both genetic and environmental factors are likely to play a role
      when the cranial nerves and ocular muscles are developing between the 4th and the
      8th week of gestation. New data from eye movement recordings contributed to
      better understanding the binocular control of saccades. Modeling of saccades in
      DRS seems promising for the quantification of the innervational deficit and the
      mechanical properties of the eye plant. The usual clinical classification of DRS
      needs to be updated in order to match more accurately the underlying
      dysinnervation of the extra ocular muscles and to illustrate the continuum that
      exists between the various forms. This review aims to summarize the major
      findings about DRS and to guide the clinician in the surgical management of this
      particular form of strabismus.

PMID- 20801149
TI  - Anticonvulsive effect of vitamin C on pentylenetetrazol-induced seizures in
      immature rats.
AB  - Vitamin C helps to prevent brain oxidative stress and participate in the
      synthesis of progesterone. It also possesses a progesterone-like effect and acts
      synergistically with progesterone on the brain. Progesterone and its metabolites,
      but also vitamin C have been associated with anticonvulsant effects. We evaluated
      the progesterone concentration 30min and 24h after the last administration of
      vitamin C (500mg/kg, i.p. for five days). We also evaluated how vitamin C altered
      pentylenetetrazol (PTZ)-induced seizures by measuring the onset latency of
      seizures, percentage of incidence and mortality as well as amino acid levels
      after seizures. Vitamin C treatment alone increased basal progesterone
      concentrations to 531% after 30min compared to 253% after 24h. Furthermore,
      vitamin C significantly increased the latency to the first myoclonic, clonic and
      tonic seizure induced by PTZ (80mg/kg, i.p.) and decreased the percentage of
      incidence of clonic and tonic seizures as well as the mortality rate. Changes in
      tissue concentration of amino acids were primarily observed at 24h after vitamin
      C treatment. Our results suggest that vitamin C together with progesterone and/or
      its metabolites are involved in the protection against PTZ-induced seizures in
      immature rats.

PMID- 20801150
TI  - Basolateral amygdala opioids contribute to increased high-fat intake following
      intra-accumbens opioid administration, but not following 24-h food deprivation.
AB  - Previous research has demonstrated that administration of MU-opioid receptor
      agonists into the nucleus accumbens increases high-fat diet consumption in sated
      rats and has shown a role of basolateral amygdala (BLA) activity in mediating
      this response. The present experiments were conducted to examine the role of BLA
      opioid transmission in mediating high-fat feeding driven by either intra
      accumbens opioid activation or 24-h home cage food deprivation. Injection of the
      MU-opioid agonist, d-Ala2-NMe-Phe4-Glyol5-enkephalin (DAMGO) into the nucleus
      accumbens (0.25MUg/0.5MUl/side) increased consumption of a high-fat diet, and
      this effect was attenuated by pre-treatment with the opioid antagonist,
      naltrexone (5MUg/0.25MUl/side) administered into the BLA. In contrast, intra-BLA
      naltrexone administration had no influence on the increase in high-fat intake
      following 24-h food deprivation. These findings suggest that BLA opioid
      transmission is an important mediator of palatability-driven feeding as modeled
      by intra-accumbens opioid activation, while BLA opioid transmission has no
      significant influence on the increase in high-fat feeding driven by short-term
      negative-energy balance.

PMID- 20801151
TI  - A diverse development of 5-HT1A receptor binding is relevant to behavioral
      differences observed in adult mice of two genetically closely related inbred
      strains.
AB  - Only few genetic loci were supposed to be crucial for strong behavioral
      differences, especially in locomotion and aggression, in two closely related mice
      inbred strains: AB/Halle (ABH) and AB/Gatersleben (ABG). Previously we reported
      remarkable strain differences in 5-HT1A receptor binding in adult mice. In the
      present study, we were interested if the strain-specific 5-HT1A receptor binding
      pattern is already present very early in ontogeny which could indirectly hint at
      a gene that is differentially regulated in these 2 mouse strains. Since the 5
      HT1A receptor is involved in the regulation of locomotion and aggression, one
      genetic determinate for the behavioral differences in ABH and ABG mice would have
      been found. Therefore, we measured [3H]8-OH-DPAT specific binding at postnatal
      day (PND) 1 and 21 (weanlings) using in vitro autoradiography. 5-HT1A receptor
      binding was not significantly different at PND 1 between strains. However, in
      weanlings the same 5-HT1A receptor binding pattern was observed as in adults,
      i.e. ABH mice display a higher forebrain 5-HT1A receptor binding compared to ABG
      mice. So the strain-specific forebrain 5-HT1A receptor binding pattern develops
      during the first 3 postnatal weeks and genetically driven mechanisms seem to be
      crucial. However, early environmental influences, e.g. differences in maternal
      care, can't be excluded.

PMID- 20801152
TI  - Agmatine inhibits morphine-induced memory impairment in the mouse step-down
      inhibitory avoidance task.
AB  - The effect of agmatine on memory formation in morphine-treated mice on the step
      down inhibitory avoidance test was examined. Pre-training and pre-test
      administration of agmatine (5, 10 and 20mg/kg, s.c.) facilitated memory formation
      and retrieval while post-training administration of agmatine (5, 10 and 20mg/kg,
      s.c.) had no effect on memory consolidation. Idazoxan (5mg/kg, i.p.) inhibited
      the effect of agmatine on memory formation and retrieval. Pre-training
      administration of morphine (1.25, 2.5 and 5mg/kg, s.c.) impaired memory formation
      while post-training and pre-test administration of morphine (1.25, 2.5 and
      5mg/kg, s.c.) had no effect on memory consolidation and retrieval. Pre-training
      agmatine treatment reversed the impairment of morphine on memory formation.
      Moreover, pre-test administration of agmatine inhibited morphine-induced amnesia.
      Pre-training and pre-test idazoxan (5mg/kg, i.p.) treatment inhibited the effect
      of agmatine on morphine induced memory impairment. In conclusion, agmatine
      inhibited morphine-induced memory impairment on the mice step-down inhibitory
      avoidance test. The mechanism was exerted, at least in part, through activation
      of imidazoline receptors.

PMID- 20801153
TI  - Are workplace interventions to reduce sitting effective? A systematic review.
AB  - OBJECTIVE: To systematically review the effectiveness of workplace interventions
      for reducing sitting. METHODS: Studies published up to April 2009 were identified
      by literature searches in multiple databases. Studies were included if they were
      interventions to increase energy expenditure (increase physical activity or
      decrease sitting); were conducted in a workplace setting; and specifically
      measured sitting as a primary or secondary outcome. Two independent reviewers
      assessed methodological quality of the included studies, and data on study
      design, sample, measures of sitting, intervention and results were extracted.
      RESULTS: Six studies met the inclusion criteria (five randomised trials and one
      pre-post study). The primary aim of all six was to increase physical activity;
      all had reducing sitting as a secondary aim. All used self-report measures of
      sitting; one specifically assessed occupational sitting time; the others used
      measures of general sitting. No studies showed that sitting decreased
      significantly in the intervention group, compared with a control or comparison
      group. CONCLUSION: Currently, there is a dearth of evidence on the effectiveness
      of workplace interventions for reducing sitting. In light of the growing body of
      evidence that prolonged sitting is negatively associated with health, this
      highlights a gap in the scientific literature that needs to be addressed.

PMID- 20801155
TI  - Smoking habits among university students in Florence: is a medical degree course
      the right choice?

PMID- 20801154
TI  - Correlates of kidney stone disease differ by race in a multi-ethnic middle-aged
      population: the ARIC study.
AB  - OBJECTIVE: To identify correlates of kidney stone disease in white and African
      American men and women in a population-based longitudinal study starting in four
      US communities, and to assess differences in correlates across racial groups.
      METHODS: Between 1993 and 1995, 12,161 middle-aged participants of the ARIC Study
      provided information on history of kidney stone disease. Information on incident
      kidney stone-related hospitalizations was obtained from ICD codes on hospital
      discharge records. RESULTS: Kidney stone disease was reported by 12.0% of men and
      4.8% of women. After multivariable adjustment, prevalent kidney stone disease was
      significantly (p<0.05) associated with male gender (PR=2.50), increased serum
      triglycerides (PR=1.07 per SD increase), diabetes (PR=1.27), gallstone disease
      (PR=1.54), white race (PR=1.67), and region of residence. Male gender (HR=1.70),
      diabetes (HR=1.98), and hypertension (HR=1.69) were significantly associated
      (p<0.05) with incident kidney stone-related hospitalizations (n=94). Race
      stratified analyses showed stronger associations of prevalent kidney stone
      disease with increased triglycerides, older age, and gallstone disease in African
      Americans compared to whites, whereas male gender showed stronger association in
      whites (all p-interaction<0.05). CONCLUSION: We identified novel correlates of
      kidney stone disease (triglycerides, gallstone disease) and risk factor
      interactions by race (age, male gender, triglycerides, gallstone disease).

PMID- 20801157
TI  - Modeling the vagus nerve system with the Unified Modeling Language.
AB  - Traditionally, the means of describing anatomical and physiological structures of
      the autonomic nervous system is natural language, drawings and images as
      represented in the scientific literature. In behavioral studies of this system,
      mathematical and electrical models and computer simulation tools are in use. In
      this article, we propose the use of the Unified Modeling Language to describe and
      specify the anatomical and physiological structures and indicate how these can be
      enriched to capture the behavioral view as well. Using the metamodel facilities
      of the language, we propose a domain specific language that captures the domain
      concepts, their relationships and constraints. Application of the language is
      demonstrated by modeling the vagus nerve in part.

PMID- 20801156
TI  - Identification and functional characterization of an Rbx1 in an invertebrate
      Haliotis diversicolor supertexta.
AB  - Rbx1 (RING box1) is an evolutionarily conserved RING-H2 finger protein and
      belongs to the RING-finger family of Ubiquitin ligase E3, which determines the
      substrate specificity of ubiquitination and regulates a variety of biological
      processes. We report here the identification and functional characterization of
      an Rbx1 homologue in abalone, which we named ab-Rbx1. Ab-Rbx1 contains conserved
      cysteine/histidine residues which are the characteristics of Rbx proteins.
      Phylogenetic tree analysis further demonstrated that ab-Rbx1 belongs to the Rbx1
      family other than Rbx2 family. Real-time PCR analysis revealed that ab-Rbx1 was
      ubiquitously expressed in all examined tissues of abalone and the expression
      level of ab-Rbx1 was significantly induced by mitogenic situation.
      Immunohistochemical and immunofluorescent staining showed that the ab-Rbx1 was
      expressed predominantly in epithelial cells and localized both in the cytoplasmic
      and nuclear compartment. Ubiquitination assay demonstrated that ab-Rbx1 had
      ubiquitin ligase activity and could auto-ubiquitinated itself. These results
      suggest that ab-Rbx1 is an Rbx1 homologue and may be indirectly involved in the
      immune response of abalone through ubiquitination.

PMID- 20801158
TI  - The effects of VTA NMDA receptor antagonism on reward-related learning and
      associated c-fos expression in forebrain.
AB  - The mechanisms whereby reward-associated stimuli come to function as conditioned
      stimuli and acquire the capacity to activate the same neural regions activated by
      primary rewards (i.e., dopamine terminal regions) is not fully understood. We
      hypothesized that NMDA receptor stimulation in the VTA is necessary for the
      acquisition by a CS to both produce conditioned approach and activate dopamine
      terminal regions. Rats were tested in a conditioned approach protocol that
      consisted of light stimulus-food conditioning sessions (30 randomly presented
      light stimulus-food pellet pairings), a session with no stimuli or food and 1
      session with only light stimulus (CS-only) presentations. Food trough head
      entries during the CS and just prior to the CS were recorded and a CS/pre-CS
      ratio indicating the conditioned approach response was calculated. Brain tissue
      was harvested after the CS-only session and processed for c-fos expression in
      prefrontal cortex area 2, nucleus accumbens core and shell and medial and lateral
      caudate. When bilateral intra-VTA microinjections of AP-5 (0, 0.25 or 0.5 MUg)
      were made prior to each of the conditioning sessions the 0.5 MUg AP-5 dose
      prevented the acquisition of conditioned approach; when 0.5 MUg AP-5 injections
      were made prior to the CS-only test they failed to affect expression of the
      response. Also, 0.5 MUg AP-5 prior to conditioning significantly reduced c-fos
      expression in response to the CS in nucleus accumbens core. These results suggest
      that VTA NMDA receptor stimulation is necessary for both the acquisition of
      reward-related learning and acquisition by the CS to activate dopamine terminal
      regions.

PMID- 20801159
TI  - The relationships between trait anxiety, place recognition memory, and learning
      strategy.
AB  - Rodents learn to navigate mazes using various strategies that are governed by
      specific regions of the brain. The type of strategy used when learning to
      navigate a spatial environment is moderated by a number of factors including
      emotional states. Heightened anxiety states, induced by exposure to stressors or
      administration of anxiogenic agents, have been found to bias male rats toward the
      use of a striatum-based stimulus-response strategy rather than a hippocampus
      based place strategy. However, no study has yet examined the relationship between
      natural anxiety levels, or trait anxiety, and the type of learning strategy used
      by rats on a dual-solution task. In the current experiment, levels of inherent
      anxiety were measured in an open field and compared to performance on two
      separate cognitive tasks, a Y-maze task that assessed place recognition memory,
      and a visible platform water maze task that assessed learning strategy. Results
      indicated that place recognition memory on the Y-maze correlated with the use of
      place learning strategy on the water maze. Furthermore, lower levels of trait
      anxiety correlated positively with better place recognition memory and with the
      preferred use of place learning strategy. Therefore, competency in place memory
      and bias in place strategy are linked to the levels of inherent anxiety in male
      rats.

PMID- 20801160
TI  - Learning, memory and search strategies of inbred mouse strains with different
      visual abilities in the Barnes maze.
AB  - Visuo-spatial learning and memory were assessed in male and female mice of 13
      inbred strains on a small diameter mouse version of the Barnes maze surrounded by
      a wall and intra-maze visual cues. Mice completed acquisition and reversal
      training to assess learning, followed by a probe test to assess memory for the
      spatial location of the escape hole. The C57BL/6J and CAST/EiJ strains showed
      better learning performance than the other strains. A/J and 129/SvImJ strains
      showed poor learning performance, which may be due to their low rates of
      exploration. No differences in memory were found between strains in the probe
      test. Males showed better learning performance than females in the DBA/2J and
      C3H/HeJ strains, but there were no sex differences in the other strains. However,
      mice may not have used visuo-spatial cues to locate the escape hole in this maze,
      as (1) all strains primarily used the non-spatial serial/thigmotaxic search
      strategy, (2) no strains showed a reversal effect when the escape hole location
      was moved, and (3) learning and memory performance were not correlated with
      measures of visual ability. Multivariate and univariate analyses of variance
      indicated that mice with good visual ability performed better than mice with poor
      visual ability, but the effect sizes were small. The small diameter of the maze
      and the presence of a wall around the edge of the maze may promote thigmotaxis in
      mice, increasing the use of a non-visual search strategy, thereby reducing the
      influence of vision on performance and decreasing the sensitivity of this maze
      design to detect strain differences in visuo-spatial learning and memory. These
      results indicate that the design of the Barnes maze has a significant effect on
      learning and memory processes.

PMID- 20801161
TI  - Classical and instrumental conditioning of eyeblink responses in Wistar-Kyoto and
      Sprague-Dawley rats.
AB  - Wistar-Kyoto (WKY) rats, an animal model of anxiety vulnerability, acquire lever
      press avoidance faster than outbred Sprague-Dawley (SD) rats. Faster avoidance
      acquisition may reflect an inherent ability to acquire cue-outcome associations,
      response-outcome associations or both. To evaluate cue-outcome learning,
      acquisition of classically conditioned eyeblink response was compared in SD and
      WKY rats using a delay-type paradigm (500-ms conditioned stimulus (CS)
      coterminating with a 10-ms unconditional stimulus (US)). WKY rats demonstrated
      enhanced classical conditioning, with both faster acquisition and greater
      asymptotic performance in delay-type training than SD rats. To evaluate response
      outcome learning, separate SD and WKY rats were given control over US delivery
      through imposition of an omission contingency into delay-type training (emitting
      a conditioned response (CR) prevented delivery of the US). The schedule of US
      delivery derived by these rats became the training regimen for a separate group
      of SD and WKY rats, yoked within strain. In SD rats, no differences in
      acquisition were detected between those given control over US delivery and those
      trained with the same partial reinforcement schedule. Acquisition rates of those
      WKY rats with control exceeded those trained with a yoked-schedule of US
      presentation. Collectively, WKY rats exhibit enhanced classical conditioning and
      sensitivity to schedules of reinforcement compared to outbred SD rats. Anxiety
      vulnerability, in particular inhibited temperament, may be traced to active
      processes in the prediction and control of aversive events.

PMID- 20801162
TI  - Effects of intracerebral ventricular administration of gastrin-releasing peptide
      and its receptor antagonist RC-3095 on learned fear responses in the rat.
AB  - Several lines of evidence have implicated bombesin and its mammalian analogue,
      gastrin-releasing peptide (GRP), in the mediation and/or modulation of the stress
      response. However, the physiological role of GRP in mediating conditioned fear
      responses remains to be elucidated. The objective of the present study was to
      characterize the role(s) of GRP and its receptor antagonist (D-Tpi6, Leu13
      psi[CH2NH]-Leu14) BB((6-14)) (RC-3095) in fear-related responses using two animal
      models of conditioned fear. To this end, the effects of intracerebroventricular
      (i.c.v.) administration of GRP (0.062, 0.30, 3.0 nmol) and RC-3095 (0.3, 3.0 and
      9.0 nmol) were assessed in the conditioned emotional response (CER) and the fear
      potentiated startle (FPS) paradigms. In the CER paradigm, i.c.v. administration
      of GRP dose-dependently (all doses) attenuated the expression of both contextual
      and cued fear as reflected by a reduction in freezing behavior to both the
      context (cage where shock was received) and cue (tone paired with shock).
      Conversely, pretreatment with RC-3095 (high dose), blocked the reduction of
      contextual and cued fear normally observed over time. Further, in the FPS
      paradigm, i.c.v. administration of GRP significantly attenuated the fear
      potentiated startle response at medium and high doses without affecting basal
      startle amplitude. In contrast, pretreatment with RC-3095 at the highest dose
      (9.0 nmol) significantly increased the basal startle amplitude without affecting
      fear-potentiation, suggesting elevated fear at the onset of testing. These data
      provide further evidence that GRP is involved in conditioned fear responses.

PMID- 20801163
TI  - Crystal structure of Leishmania major ADP-ribosylation factor-like 1 and a
      classification of related GTPase family members in this Kinetoplastid.
AB  - ADP-ribosylation factor-like (ARL) proteins are small GTPases that undergo
      conformational changes upon nucleotide binding, and which regulate the affinity
      of ARLs for binding other proteins, lipids or membranes. There is a paucity of
      structural data on this family of proteins in the Kinetoplastida, despite studies
      implicating them in key events related to vesicular transport and regulation of
      microtubule-dependent processes. The crystal structure of Leishmania major ARL1
      in complex with GDP has been determined to 2.1 A resolution and reveals a high
      degree of structural conservation with human ADP-ribosylation factor 1 (ARF1).
      Putative L. major and Trypanosoma brucei ARF/ARL family members have been
      classified based on structural considerations, amino acid sequence conservation
      combined with functional data on Kinetoplastid and human orthologues. This
      classification may guide future studies designed to elucidate the function of
      specific family members.

PMID- 20801164
TI  - Eimeria bovis-induced modulation of the host cell proteome at the meront I stage.
AB  - The proteome of Eimeria bovis meront I-carrying host cells was analyzed by two
      dimensional gel electrophoresis (2DE) at 14 days p.i. and compared to non
      infected control cells. A total of 221 protein spots were modulated in their
      abundance in E. bovis-infected host cells and were subsequently analyzed by
      matrix-assisted laser desorption ionization time-of-flight mass spectometry
      (MALDI-TOF-MS). These analyses identified 104 proteins in total with 25 host cell
      proteins being up-regulated and 79 proteins being down-regulated in E. bovis
      infected host cells. Moreover, 20 newly expressed proteins were identified
      exclusively in E. bovis-infected host cells and were most likely of parasite
      origin. Parasite-induced differences in protein abundance concerned distinct
      functional categories, with most proteins being involved in host cell metabolism,
      cell structure, protein fate and gene transcription. Some of the modulated
      molecules also indicated regulatory processes on the level of host cell stress
      response (HSP70, HSP90), host cell apoptosis (caspase 8) and actin
      elongation/depolymerization (alpha-actinin-1, gelsonin, tropomodulin-3,
      transgelin). Since merozoites I were already released shortly after cell
      sampling, the current data reflect the situation at the end of first merogony.
      This is the first proteomic approach on E. bovis-infected host cells that was
      undertaken to gain a rather broad insight into Eimeria-induced host cell
      modulation. The data processed in this investigation should provide a useful
      basis for more detailed analyses concerning Eimeria-host cell interactions.

PMID- 20801165
TI  - Corticotropin releasing factor-distribution in rat intestine and role in
      neuroprotection.
AB  - Aims of the present study were to describe the distribution of corticotropin
      releasing factor (CRF) immunoreactivity in rat small and large intestines, to
      quantify the percentage of CRF-immunoreactive (CRF-IR) enteric neurons, to reveal
      possible CRF immunoreactivity in cultured myenteric neurons from rat ileum and to
      examine if additions of CRF, urocortin 1 (Ucn1), CRF antagonist or vasoactive
      intestinal peptide (VIP) affect neuronal survival in vitro. Co-localization of
      CRF- and VIP-immunoreactivity was examined, as well as a possible interplay
      between CRF and VIP in neuroprotection. Further we wanted to elucidate if mast
      cells affect neuronal survival via CRF signaling. Networks of CRF-containing
      nerve cell bodies and fibers were detected in rat intestine. CRF-IR neurons
      contained to a high degree also VIP. A low number of cultured myenteric neurons
      was CRF-IR. CRF, Ucn1 or CRF-antagonist did not promote neuronal survival of
      cultured myenteric neurons, while VIP significantly enhanced neuronal survival.
      Simultaneous presence of CRF attenuated the VIP mediated increase in neuronal
      survival. Co-culturing neurons and mast cells resulted in a marked reduction in
      neuronal survival, not executed via CRF signaling pathways. CONCLUSION: CRF is
      present in enteric neurons and counteracts the neuroprotective effect of VIP in
      vitro.

PMID- 20801166
TI  - Development of an up-converting phosphor technology-based 10-channel lateral flow
      assay for profiling antibodies against Yersinia pestis.
AB  - In this study, a 10-channel up-converting phosphor technology-based lateral flow
      (TC-UPT-LF) assay was developed to profile antibodies against Yersinia pestis.
      Ten expressed Y. pestis proteins were covalently conjugated with an up-converting
      phosphor particle to develop double-antigen sandwich immunochromatographic strips
      to detect corresponding antibodies. After optimization one by one, each strip was
      integrated into a TC-UPT-LF disc for simultaneously detection of different
      antibodies. A scanning biosensor was also developed to acquire the results. The
      performance of the TC-UPT-LF assay was evaluated by using standard samples and
      plague monkey serum samples. Fifty-one patient serum samples were detected by the
      TC-UPT-LF assay. The TC-UPT-LF disc could be stable for 10 days at 37 degrees C
      with an average CV of 10.3%. Its sensitivity and qualitative results are
      comparable to those of ELISA. Its linearity fitting coefficient of determination
      (R2) for different antibody detection is between 0.93 and 0.99. Besides F1
      antibody, the LcrV and YopD antibodies also showed higher positive ratio than the
      other seven antibodies, as 100% (13/13) and 92% (12/13) in monkey sera and 86.3%
      (44/51) and 66.7% (34/51) in patient sera, respectively. It is suggested that the
      TC-UPT-LF assay has been successfully developed for multi-detection and LcrV and
      YopD can be the potential diagnostic markers of the plague.

PMID- 20801167
TI  - Improved performance of the modified Hodge test with MacConkey agar for screening
      carbapenemase-producing Gram-negative bacilli.
AB  - The detection of carbapenemases in Gram-negative bacilli is important for optimal
      patient treatment and to control spread of the resistance. The modified Hodge
      test can detect carbapenemase-producing Gram-negative bacilli. In this study, we
      compared the performance of MacConkey agar and Mueller-Hinton agar for metallo
      beta-lactamase (MBL) and OXA carbapenemase screening. Overall, the performance of
      Hodge test was better with MacConkey agar due to enhanced release of beta
      lactamases from the cells in the presence of bile compounds. Concomitant use of
      the modified Hodge test could resolve most of the problems with uncertain double
      disk synergy tests in MBL detection.

PMID- 20801168
TI  - A duplex PCR method to identify mosaic penA gene and predict reduced
      susceptibility to oral cephalosporins in Neisseria gonorrhoeae.
AB  - Neisseria gonorrhoeae with mosaic penicillin-binding protein 2 (PBP2) is
      associated with reduced susceptibility to third-generation oral cephalosporins. A
      simple and rapid PCR method using three primers was designed to identify mosaic
      PBP2, which could help predict reduced susceptibility to expanded-spectrum
      cephalosporins in N. gonorrhoeae.

PMID- 20801169
TI  - Real-time PCR detection of Holophagae (Acidobacteria) and Verrucomicrobia
      subdivision 1 groups in bulk and leek (Allium porrum) rhizosphere soils.
AB  - In the light of the poor culturability of Acidobacteria and Verrucomicrobia
      species, group-specific real-time (qPCR) systems were developed based on the 16S
      rRNA gene sequences from culturable representatives of both groups. The number of
      DNA targets from three different groups, i.e. Holophagae (Acidobacteria group 8)
      and Luteolibacter/Prosthecobacter and unclassified Verrucomicrobiaceae
      subdivision 1, was determined in DNA extracts from different leek (Allium porrum)
      rhizosphere soil compartments and from bulk soil with the aim to determine the
      distribution of the three bacterial groups in the plant-soil ecosystem. The
      specificity of the designed primers was evaluated in three steps. First, in
      silico tests were performed which demonstrated that all designed primers 100%
      matched with database sequences of their respective groups, whereas lower matches
      with other non-target bacterial groups were found. Second, PCR amplification with
      the different primer sets was performed on genomic DNA extracts from target and
      from non-target bacteria. This test demonstrated specificity of the designed
      primers for the target groups, as single amplicons of expected sizes were found
      only for the target bacteria. Third, the qPCR systems were tested for specific
      amplifications from soil DNA extracts and 48 amplicons from each primer system
      were sequenced. All sequences were >97% similar to database sequences of the
      respective target groups. Estimated cell numbers based on Holophagae-,
      Luteolibacter/Prosthecobacter- and unclassified Verrucomicrobiaceae subdivision 1
      specific qPCRs from leek rhizosphere compartments and bulk soils demonstrated
      higher preference for one or both rhizosphere compartments above bulk soil for
      all three bacterial groups.

PMID- 20801170
TI  - A rapid microtiter plate assay for measuring the effect of compounds on
      Staphylococcus aureus membrane potential.
AB  - We developed a homogenous microtiter based assay using the cationic dye 3, 3'
      Diethyloxacarbocyanine iodide, DiOC2(3), to measure the effect of compounds on
      membrane potential in Staphylococcus aureus. In a screen of 372 compounds from a
      synthetic compound collection with anti-Escherichia coli activity due to unknown
      modes of action at least 17% demonstrated potent membrane activity, enabling
      rapid discrimination of nuisance compounds.

PMID- 20801171
TI  - Novel plasmid-based genetic tools for the study of promoters and terminators in
      Streptococcus pneumoniae and Enterococcus faecalis.
AB  - Promoter-probe and terminator-probe plasmid vectors make possible to rapidly
      examine whether particular sequences function as promoter or terminator signals
      in various genetic backgrounds and under diverse environmental stimuli. At
      present, such plasmid-based genetic tools are very scarce in the Gram-positive
      pathogenic bacteria Streptococcus pneumoniae and Enterococcus faecalis. Hence, we
      developed novel promoter-probe and terminator-probe vectors based on the
      Streptococcus agalactiae pMV158 plasmid, which replicates autonomously in
      numerous Gram-positive bacteria. As reporter gene, a gfp allele encoding a
      variant of the green fluorescent protein was used. These genetic tools were shown
      to be suitable to assess the activity of promoters and terminators (both
      homologous and heterologous) in S. pneumoniae and E. faecalis. In addition, the
      promoter-probe vector was shown to be a valuable tool for the analysis of
      regulated promoters in vivo, such as the promoter of the pneumococcal fuculose
      kinase gene. These new plasmid vectors will be very useful for the experimental
      verification of predicted promoter and terminator sequences, as well as for the
      construction of new inducible-expression vectors. Given the promiscuity exhibited
      by the pMV158 replicon, these vectors could be used in a variety of Gram-positive
      bacteria.

PMID- 20801172
TI  - Capturing SCL and HR changes to win and loss events during gambling on electronic
      machines.
AB  - The role of physiological arousal is central to theories about the onset and
      maintenance of gambling behaviours including problem gambling. The range of
      possibilities suggested include tonic underarousal and phasic abnormalities such
      as hypersensitivity to reward and/or reduced sensitivity to negative consequences
      associated with losses. Among the various types of gambling, electronic gambling
      machines (EGMs) are associated with the large majority of gambling related
      problems. The demonstration that physiological changes associated with rapidly
      occurring win and loss events during electronic gambling can be reliably captured
      is fundamental to further progress in the psychophysiology of gambling. The
      current study monitored electrodermal and cardiac activities of twenty-four
      healthy participants to event outcomes (losses, fake wins, small wins and big
      wins) during a task on a real EGM. The results demonstrated that it is possible
      to reliably capture the profile of physiological changes as they occurred in real
      time to the many different win and loss events during electronic gambling.
      Relative to baseline levels, win events produced significant increases in skin
      conductance levels, (but not in HR) whereas loss events produced no significant
      changes. The study has important applications for further experimental and
      clinical research.

PMID- 20801173
TI  - The ever-expanding diversity of porcine reproductive and respiratory syndrome
      virus.
AB  - Porcine reproductive and respiratory syndrome (PRRS) virus appeared 20 years ago
      as the cause of a new disease in swine. Today PRRS is the most significant swine
      disease worldwide in spite of intensive immunological interventions. The virus
      showed remarkable genetic variation with two geographically distinct genotypes at
      the time of its discovery, indicating the possibility of prolonged evolutionary
      divergence prior to its appearance as a swine pathogen. Since then, both type 1
      and type 2 have spread geographically, radiated genetically, and acquired new
      phenotypic characteristics, especially increased virulence. Here, we explore
      various hypotheses that might account for rapid expansion and diversification of
      PRRSV, including mechanisms specific to PRRSV and other arteriviruses, cellular
      modification processes, and immunological selection. Phylogenetic analysis of
      PRRSV has provided a broadly applicable means to relate diverse isolates, but it
      does not explain biological variation in virulence or immunological cross
      protection. We present other methods of classification and review their
      limitations. Major questions about PRRSV remain unanswered despite intensive
      investigation, suggesting that the interaction of PRRSV with pigs involves novel
      biological processes that may be relevant to other RNA virus and host
      interactions.

PMID- 20801175
TI  - Functional integrity of naturally occurring mutants of HIV-1 subtype C Vpr.
AB  - HIV-1 Vpr, an accessory protein with multiple functions, is involved in the
      induction of apoptosis, cell cycle G2 arrest, and modulation of gene expression.
      Many functions of this protein have been documented for the wild-type subtype B
      Vpr, however the functionality of other subtypes has not sufficiently been
      addressed. In this study, the functionality of Subtype B Vpr, 6 subtype C mutant
      Vpr proteins and the consensus sequence of subtype C Vpr were compared with each
      other. All the subtype B and C Vpr proteins localized to the nucleus of human
      293T cells. Subtype C Vpr proteins induced cell cycle G2 arrest in a lower
      proportion of human 293T cells compared to subtype B Vpr. Subtype B and the
      naturally mutant Vpr proteins induced apoptosis in a similar manner, ranging from
      95.33% to 98.64%. However, an artificially designed Vpr protein containing the
      consensus sequences of subtype C Vpr indicated a reduced ability in induction of
      apoptosis. The study of mRNA profile of the transfected cells indicated that all
      Vpr proteins modulated the apoptotic genes triggering the intrinsic pathway of
      apoptosis. Our results indicate that subtype C Vpr is able to exert the same
      functions previously reported for subtype B Vpr. Most natural mutations in Vpr
      not only do not disturb the functions of the protein but also potentiate the
      protein for an increased functionality. The natural mutations of Vpr may thus not
      always be regarded as defective mutations. The study suggests the adaptive role
      of the natural mutations commonly found in subtype C Vpr.

PMID- 20801174
TI  - Enhanced transduction efficiency of fiber-substituted adenovirus vectors by the
      incorporation of RGD peptides in two distinct regions of the adenovirus serotype
      35 fiber knob.
AB  - Fiber-substituted Ad serotype 5 vectors containing the fiber protein from Ad
      serotype 35 (Ad5F35) exhibit properties that render them suitable as a platform
      for targeted Ad vectors. Ad5F35 vectors do not show apparent tropism in certain
      organs, including the liver, and they elicit less innate immunity than other
      vectors after intravenous administration. In order to develop a targeted Ad
      vector, we previously developed fiber-mutant Ad5F35 vectors containing the
      integrin binding Arg-Gly-Asn (RGD) motif in the FG or HI loop of the Ad35 fiber
      knob. Mutant Ad5F35 vectors containing the RGD peptide in the FG or HI loop
      transduced CD46-negative cells more efficiently in an RGD-dependent manner, as
      compared to the efficiency achieved with unmodified Ad5F35 vectors (Matsui et
      al., 2009. Gene Therapy 16, 1050-1057). However, the transduction efficiency of
      the mutant Ad5F35 vectors in CD46-negative cells remained lower than had been
      expected. Ad5F35 vectors containing the RGD peptide in the HI or FG loop enabled
      a 6-fold higher transduction efficiency than that achieved with unmodified Ad5F35
      vectors in CD46-negative cells, although this cell type abundantly expresses
      alpha(v)-integrins. In the present study, we aimed to enhance the transduction
      efficiency of fiber-mutant Ad5F35 vectors. To this end, we developed an Ad5F35
      vector system in which foreign peptides could be incorporated into regions of FG
      and HI loops of the Ad35 fiber knob by means of in vitro ligation. Using this
      Ad5F35-vector system, firefly luciferase-expressing mutant Ad5F35 vectors
      containing the RGD peptides in both loops (Ad5F35-2xRGD-L2) were constructed. In
      CD46-negative cells, Ad5F35-2xRGD-L2 showed 12-fold and 3-fold greater
      transduction efficiency than unmodified Ad5F35 vectors and mutant Ad5F35 vectors
      containing only one copy of the RGD peptide in the FG or the HI loop. In
      addition, transduction with Ad5F35-2xRGD-L2 in CD46-negative cells was RGD
      peptide-dependent. These results indicate that fiber-mutant Ad5F35 vectors, by
      which foreign peptides can be simultaneously incorporated into both the FG and
      the HI loops of the Ad35 fiber knob, could be a promising gene delivery vehicle
      for various gene therapies, and could facilitate basic research efforts such as
      analyses of gene function.

PMID- 20801176
TI  - The infection of mammalian and insect cells with SFV bearing nsP1 palmitoylation
      mutations.
AB  - Semliki Forest virus (SFV), an alphavirus, replicates in vertebrate host and
      mosquito vector cells. The virus-specific part of the replicase complex
      constitutes nonstructural proteins 1-4 (nsP1-nsP4) and is bound to cytoplasmic
      membranes by an amphipathic helix inside of nsP1 and through the palmitoylation
      of cysteine residues in nsP1. In mammalian cells, defects in these viral
      functions result in a nonviable phenotype or the emergence of second-site
      compensatory mutations that have a positive impact on SFV infection. In most
      cases, these second-site compensatory mutations were found to compensate for the
      defect caused by the absence of palmitoylation in mosquito cells (C6/36). In
      C6/36 cells, however, all palmitoylation-defective viruses had severely reduced
      synthesis of subgenomic RNA; at the same time, several of them had very efficient
      formation of defective interfering genomes. Analysis of C6/36 cells that
      individually expressed either wild type (wt) or palmitoylation-deficient nsP1
      forms revealed that similar to mammalian cells, the wt nsP1 localized
      predominantly to the plasma membrane, whereas its mutant forms localized to the
      cytoplasm. In contrast to transfected mammalian cells, all forms of nsP1 induced
      the formation of filopodia-like structures on some, but not all, transfected
      mosquito cells. These findings indicate that the plasma membrane and associated
      host factors may have different roles in alphavirus replicase complex formation
      in mammalian and mosquito cells. In general, the lack of nsP1 palmitoylation had
      a less severe effect on the function of the replication complex in mammalian
      cells when compared with that in mosquito cells.

PMID- 20801177
TI  - Apple and peach consumption habits across European countries.
AB  - The aim of this study was to gain information concerning apple and peach
      consumption frequency within different European countries in relation to age and
      gender. The survey was a part of a complex experiment with the aim of evaluating
      consumers' preferences towards new varieties, and the data is based on the self
      reported declarations of respondents, male and female, between 15 and 70 years
      old. 4271 consumers from 7 European countries were invited to supply information
      about their apple consumption habits, whereas 499 respondents from 5 countries
      answered questions relating to frequency of peach and nectarine consumption. In
      both, the apple and the peach surveys, data analysis of declared intake showed
      significant differences between nationalities. The highest apple consumption was
      in Poland, where over 55% declared a consumption of more than 5 apples per week.
      In comparison, Italian consumers most often indicated eating 3-5 apples per week
      (39.3%). The lowest apple consumption was in the Netherlands and Spain. In the
      case of peaches, the highest consumption was indicated in France where 48% of
      respondents declared a peach consumption of 3-5 per week with 40% eating more
      than 5 fruits per week. The lowest peach intake was declared in Germany.
      Irrespective of country women were shown to eat more apples that men.
      Furthermore, the group of older people (61-70 years) consume apples more often
      than the adult group (36-60), while within the youngest group of consumers (16
      35) eating apples was not at all popular. As with apples females declared a
      higher peach consumption, and again significantly lower fruit consumption by the
      youngest group (16-35) was indicated. Although the availability of fruit at the
      market remains a prime factor in determining apple and peach consumption, our
      survey confirmed the trends of declining this popular fruit intake by the younger
      generation, as well as the persistent tendency of lower frequency of fruit
      consumption among men than women.

PMID- 20801178
TI  - The effect of texture differences on satiation in 3 pairs of solid foods.
AB  - This study explored the effect of texture differences on satiation (ad libitum
      food intake) in 3 pairs of solid foods. Test products were specially developed
      luncheon meat, meat replacers and sweets. Each food consisted of a "hard" and
      "soft" version, expected to lead to different eating rates and consequently to
      differences in oral sensory exposure time. One hundred and six subjects
      participated in 7 sessions. During the first sessions, subjects consumed the
      products ad libitum while watching a movie in a cinema. During the last session,
      eating rate of all products was measured. Mean intake did not differ
      significantly between the hard and soft version for any of the products, but
      subjects who ate more of the soft luncheon meat significantly outnumbered
      subjects who ate more of the hard version. Eating rate was significantly slower
      for the hard than for the soft luncheon meat (21 +/- 10 vs. 25 +/- 13 g/min); no
      differences were found for the other food types. Ad libitum intake was twice as
      high in the highest versus the lowest quartile of eating rate (p < 0.001).
      Texture differences between the hard and soft versions may have been too subtle
      to lead to differences in eating rate for meat replacers and sweets and
      consequently to differences in food intake.

PMID- 20801179
TI  - Eating habits, health attitudes and obesity indices among medical students in
      northern Greece.
AB  - Medical students represent not only the final but also the most crucial
      opportunity for education in the field of healthy lifestyles and nutritional
      habits. Eating habits and obesity indices among medical students in southern
      Greece were described almost a decade ago. However, there is a lack of current,
      relevant data concerning students living in northern Greece. The purpose of the
      present study was to evaluate the body mass index distribution and nutritional
      and health-related behavior among medical students in northern Greece. The
      participants, 187 males (21.5 +/- 1.9 years) and 203 females (21.3 +/- 2.2
      years), filled out a self-report questionnaire. Height and weight measurements
      were obtained. Dietary practices of fast food consumption (more frequent for
      males) and regular consumption of fruits and vegetables (more frequent for
      females) were reported. Females seemed to adopt different practices than males
      when trying to lose weight and were significantly better informed about the
      nutrient value of the food consumed. Although the prevalence of overweight
      (males: 32.1%, females: 8.4%) and obesity (males: 5.9%, females: 1.5%) in the
      present sample is lower compared to previous data, it remains high according to
      what would be health promoting. The above findings suggest a need for further
      improvement in strategies promoting healthier nutrition habits.

PMID- 20801180
TI  - Eating behavior in obese and overweight persons with and without anhedonia.
AB  - The aim of this study was to evaluate differences in body mass index and eating
      behavior in obese and overweight persons with and without anhedonia during a
      weight loss intervention study. Psychiatric diagnostics were based on the
      Structured Clinical Interview for DSM-IV disorders. Eating behavior was assessed
      by the Three Factor Eating Questionnaire (TFEQ-18) and binge eating by the Binge
      Eating Scale (BES). Out of 82 participants, 20 (24.4%) reported experiencing
      anhedonia at least once during the study period. Those suffering from anhedonia
      scored significantly higher values in BES at baseline and at follow-up. They also
      reported more uncontrolled and emotional eating at the first follow-up. Overall,
      persons suffering from anhedonia achieved a poorer outcome in weight loss
      compared to those without anhedonia. Anhedonia was associated with uncontrolled
      eating, emotional eating, and binge eating, all of which may have contributed to
      the poorer outcomes achieved in weight loss.

PMID- 20801181
TI  - Safety assessment of Cry1C protein from genetically modified rice according to
      the national standards of PR China for a new food resource.
AB  - The Cry1C protein produced in Escherichia coli was used for in vitro evaluation
      and animal studies to support the safety assessment of GM food or feed products
      containing the Cry1C protein. The Cry1C protein does not have any sequence
      homology with known allergens or toxins. Although the Cry1C protein was heat
      stable it was rapidly degraded in vitro with simulated gastric or intestinal
      fluids. It did not cause adverse effects in mice as administered by gavage at a
      high level dosage of 5 g (Cry1C protein)/kg body weight. The mutagenicity of this
      protein was evaluated according to the national standards of People's Republic of
      China (PR China) for a new food resource. In mutagenic tests, the Cry1C protein
      caused<4 micronucleated cells per 1000 cells, <16 sperm abnormalities per 1000
      cells and was not associated with any increased mutations in the Ames test. Taken
      together, these data indicate that the Cry1C protein is not a potential allergen
      or toxin.

PMID- 20801182
TI  - Toxicogenomics and cancer risk assessment: a framework for key event analysis and
      dose-response assessment for nongenotoxic carcinogens.
AB  - In order to determine a threshold for nongenotoxic carcinogens, the traditional
      risk assessment approach has been to identify a mode of action (MOA) with a
      nonlinear dose-response. The dose-response for one or more key event(s) linked to
      the MOA for carcinogenicity allows a point of departure (POD) to be selected from
      the most sensitive effect dose or no-effect dose. However, this can be
      challenging because multiple MOAs and key events may exist for carcinogenicity
      and oftentimes extensive research is required to elucidate the MOA. In the
      present study, a microarray analysis was conducted to determine if a POD could be
      identified following short-term oral rat exposure with two nongenotoxic rodent
      carcinogens, fenofibrate and methapyrilene, using a benchmark dose analysis of
      genes aggregated in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and
      Gene Ontology (GO) biological processes, which likely encompass key event(s) for
      carcinogenicity. The gene expression response for fenofibrate given to rats for
      2days was consistent with its MOA and known key events linked to PPARalpha
      activation. The temporal response from daily dosing with methapyrilene
      demonstrated biological complexity with waves of pathways/biological processes
      occurring over 1, 3, and 7days; nonetheless, the benchmark dose values were
      consistent over time. When comparing the dose-response of toxicogenomic data to
      tumorigenesis or precursor events, the toxicogenomics POD was slightly below any
      effect level. Our results suggest that toxicogenomic analysis using short-term
      studies can be used to identify a threshold for nongenotoxic carcinogens based on
      evaluation of potential key event(s) which then can be used within a risk
      assessment framework.

PMID- 20801183
TI  - Effect of firing protocols on cohesive failure of all-ceramic crowns.
AB  - OBJECTIVES: The mechanical properties of veneering material in all-ceramic
      restorations are inferior to those of high-strength ceramics. The objective of
      this study was to assess the effect of three different firing protocols
      (different cooling times) on cohesive failure of veneered all-ceramic crowns
      using a newly developed in vitro test design. METHODS: A prepared anterior
      maxillary incisor was used to produce geometrically identical crowns (n=68) with
      a zirconia framework 0.4mm thick veneered with two different ceramics and
      prepared by use of three different firing protocols. Twenty crowns were loaded
      until fracture without artificial ageing; the other crowns underwent
      thermocycling and chewing simulation before ultimate-load testing. Statistical
      analysis was performed using non-parametric tests. RESULTS: The results showed
      that a reduced temperature decrease after firing led to better performance of all
      ceramic anterior crowns in the in vitro tests. A significant difference with
      regard to firing protocol (p=0.006) was observed for one veneering ceramic
      material only, however. CONCLUSION: It can therefore be concluded that the test
      design presented enabled sensitive measurement of the effect of firing protocol
      on cohesive failure of all-ceramic crowns. The modified firing protocol with 6min
      additional cooling time resulted in greater resistance.

PMID- 20801184
TI  - An investigation into the effect of try-in pastes, uncured and cured resin
      cements on the overall color of ceramic veneer restorations: an in vitro study.
AB  - OBJECTIVES: The aim of this study was to assess how different shades of try-in
      pastes, uncured and cured resin cements influence the overall color of porcelain
      veneer restorations. METHODS: Porcelain veneers of shade Vita 1M1 VM7 and 1mm
      thick were applied to bovine teeth using three shades of resin cement and their
      try-in paste produced by three manufacturers. Analysis of variance was carried
      out on the color difference values (DeltaE*) between the Aquagel and both the try
      in paste and cured resins. An assessment of the clinical significance of DeltaE*
      between the try-in paste and the cured resin and also between the uncured and
      cured resin was made. RESULTS: There were statistically significant differences
      in veneers' colors when using different shades of both Calibra and Nexus resin
      cements (p<0.05). Also, statistically significant differences were noticed when
      using different shades of both Rely-X and Nexus try-in pastes (p<0.05). Color
      differences produced between the try-in pastes and the corresponding shades of
      cured resin cements ranged from DeltaE* 1.05 to 3.34. The color differences
      between uncured and cured resins of the same shade ranged from DeltaE* 0.78 to
      1.41. CONCLUSIONS: Different colored try-in pastes and resin cements produced
      color changes which are clinically useful in changing the color of veneer
      restorations and therefore aid color matching to adjacent dentition. Clinically
      significant differences were found between try-in pastes and the cured resin of
      the same shade, however, there were relatively small changes measured between
      uncured and cured resins. The color match achieved by the try-in paste has to be
      treated with caution and further assessment of the restoration made with the
      resin in place before curing is recommended.

PMID- 20801185
TI  - Two imaging techniques for 3D quantification of pre-cementation space for CAD/CAM
      crowns.
AB  - OBJECTIVES: Internal three-dimensional (3D) "fit" of prostheses to prepared teeth
      is likely more important clinically than "fit" judged only at the level of the
      margin (i.e. marginal "opening"). This work evaluates two techniques for
      quantitatively defining 3D "fit", both using pre-cementation space impressions: X
      ray microcomputed tomography (micro-CT) and quantitative optical analysis. Both
      techniques are of interest for comparison of CAD/CAM system capabilities and for
      documenting "fit" as part of clinical studies. METHODS: Pre-cementation space
      impressions were taken of a single zirconia coping on its die using a low
      viscosity poly(vinyl siloxane) impression material. Calibration specimens of this
      material were fabricated between the measuring platens of a micrometre. Both
      calibration curves and pre-cementation space impression data sets were obtained
      by examination using micro-CT and quantitative optical analysis. Regression
      analysis was used to compare calibration curves with calibration sets. RESULTS:
      Micro-CT calibration data showed tighter 95% confidence intervals and was able to
      measure over a wider thickness range than for the optical technique. Regions of
      interest (e.g., lingual, cervical) were more easily analysed with optical image
      analysis and this technique was more suitable for extremely thin impression walls
      (<10-15MUm). Specimen preparation is easier for micro-CT and segmentation
      parameters appeared to capture dimensions accurately. CONCLUSIONS: Both micro-CT
      and the optical method can be used to quantify the thickness of pre-cementation
      space impressions. Each has advantages and limitations but either technique has
      the potential for use as part of clinical studies or CAD/CAM protocol
      optimization.

PMID- 20801186
TI  - Preferential beta-arrestin signalling at low receptor density revealed by
      functional characterization of the human FSH receptor A189 V mutation.
AB  - The A189 V inactivating mutation of the human FSH receptor (FSHR) leads to
      subfertility in men and primary ovarian failure in women. This mutation has
      previously been associated with intracellular retention of the FSHR and impaired
      cAMP production. Here, we show that the A189 V FSHR stably expressed in HEK293N
      cells provoked ERK MAP kinases phosphorylation through beta-arrestins,
      independently of the canonical cAMP/PKA pathway. Interesting, both the A189 V and
      wild-type (Wt) FSHRs selectively activated cAMP-independent ERK phosphorylation
      when expressed at low plasma membrane densities. These data indicate that the
      selective intracellular signalling triggered by the A189 V FSHR resulted from
      reduced membrane expression rather than by switching receptor coupling. Hence,
      receptor density at the plasma membrane might control the balance between
      distinct signal transduction mechanisms. Furthermore, our results help to clarify
      why mutations of FSHbeta are more deleterious to human fertility than the FSHR
      A189 V mutation which preserves parts of receptor signalling repertoire.

PMID- 20801187
TI  - Analysis of the effects of androgens and training on myostatin propeptide and
      follistatin concentrations in blood and skeletal muscle using highly sensitive
      immuno PCR.
AB  - Myostatin propeptide (MYOPRO) and follistatin (FOLLI) are potent myostatin
      inhibitors. In this study we analysed effects of training and androgens on MYOPRO
      and FOLLI concentrations in blood and skeletal muscle using Immuno PCR. Young
      healthy males performed either a 3-month endurance training or a strength
      training. Blood and biopsy samples were analysed. Training did not significantly
      affect MYOPRO and FOLLI concentrations in serum and muscle. To investigate
      whether total skeletal muscle mass may affect circulating MYOPRO and FOLLI
      levels, blood samples of tetraplegic patients, untrained volunteers and
      bodybuilders were analysed. MYOPRO was significantly increased exclusively in the
      bodybuilder group. In orchiectomised rats MYOPRO increased in blood and muscle
      after treatment with testosterone. In summary our data demonstrate that moderate
      training does not affect the concentrations of MYOPRO to FOLLI. In contrast
      androgen treatment results in a significant increase of MYOPRO in skeletal muscle
      and serum.

PMID- 20801188
TI  - Cognitive processing of traffic signs in immersive virtual reality environment:
      An ERP study.
AB  - The virtual reality environment can provide an immersive feeling as in the real
      word. So, using virtual reality technology to construct realistic experimental
      scenarios, the mechanism of cognitive processing in the human brain could be
      better studied. In this paper, we have designed an experiment, where through the
      presentation of traffic signs with correct or incorrect background colors in a
      virtual reality traffic environment, and studied the cognitive processing in the
      human brain using event-related potential (ERP) method. The results showed that
      whether the background colors of traffic signs were correct or not, the degrees
      of familiarity to these traffic signs in the human brain were similar, and the
      degree of contrast between the background colors and foreground colors of traffic
      signs would influence the degree of difficulty in cognitive processing. The
      degree of complexity in contents of traffic signs appears related to the
      cognitive speed in the human brain. In sum, simpler contents and larger contrast
      between the background colors and foreground colors of traffic signs would make
      the human brain respond faster.

PMID- 20801189
TI  - Retinal blood vessels are damaged in a rat model of NMDA-induced retinal
      degeneration.
AB  - Retinal ischemia-reperfusion causes capillary degeneration but the mechanisms of
      damage are not well understood. The NMDA receptor plays an important role in
      neuronal damage after ischemia-reperfusion. Therefore, we determined whether
      retinal blood vessels are damaged structurally and functionally in a rat model of
      retinal degeneration induced by NMDA. At 7 days after a single intravitreal
      injection of NMDA (200nmol) into the eye, loss of retinal ganglion cells and
      thinning of the inner plexiform layer were observed. Endothelial cells
      disappeared in some regressing vessels and empty basement membrane sleeves were
      left as remnants of the vessels. The number of basement membrane sleeves was
      increased in the NMDA-treated retina and non-perfused vessels were found in the
      injured retina. These results indicate that retinal blood vessels are damaged in
      the NMDA-induced retinal degeneration model. Neuronal cells may play a role in
      maintaining normal structure and function of the vasculature in the retina.

PMID- 20801190
TI  - Protein profiling of Guillain-Barre syndrome cerebrospinal fluid by two
      dimensional electrophoresis and mass spectrometry.
AB  - Protein profiling of cerebrospinal fluid in Guillain-Barre syndrome (GBS), an
      acute and immune-mediated disease affecting the peripheral nervous system, was
      performed by two-dimensional electrophoresis. Significant modulated spots in GBS
      patients vs. control groups (a group of multiple sclerosis patients and one of
      healthy donors) underwent MALDI-TOF/TOF investigation. Inflammation-related
      proteins, such as vitamin D-binding protein, beta-2 glycoprotein I (ApoH), and a
      complement component C3 isoform were up-regulated in GBS, whereas transthyretin
      (the monomer and the dimer forms), apolipoprotein E, albumin and five of its
      fragments were down-regulated. Then, we used an isoelectric-focusing
      dinitrophenylhydrazine-based technique to analyse the extent of carbonylation
      and, as a result, of oxidative damage of GBS CSF proteome. We observed a major
      sensitivity to carbonylation for albumin and alpha-glycoprotein in inflammation
      and a selective increase of reactivity for a glycosylated Fab from an IgM
      globulin in GBS CSF. Our results add new proteins to candidate CSF features of
      GBS, and suggest that oxidative stress could contribute to the immunopathological
      mechanisms in this syndrome.

PMID- 20801191
TI  - Chronic hypoxia- and cold-induced changes in cardiac enzyme and gene expression
      in CD-1 mice.
AB  - BACKGROUND: In mammals, environmental challenges often result in physical and
      metabolic cardiac remodeling (i.e., hypertrophy and a shift from lipid to
      carbohydrate oxidation). While chronic hypoxia and cold are both known to elicit
      cardiac changes, little is known about their combined effects. METHODS: To
      investigate the cumulated effects of these two stressors on cardiac physiology,
      CD-1 mice were exposed for 4 weeks to normoxia/normothermia, hypoxia, cold, or
      combined hypoxic-cold. We assessed physical characteristics, left ventricular
      activities of fatty acid catabolic enzymes short-chain beta-hydroxyacyl-CoA
      dehydrogenase (SCHAD) and medium-chain acyl-CoA dehydrogenase, and mRNA levels of
      Acadm, muscle- and liver-type carnitine palmitoyltransferase (Cpt-1beta, Cpt
      1alpha), and the transcriptional regulator PPARalpha. RESULTS: 1) Chronic hypoxia
      reduced SCHAD activity without physical remodeling or mRNA changes; 2) chronic
      cold lead to reduced SCHAD activity in hypertrophied left ventricles and lowered
      right ventricular Cpt-1alpha mRNA (compared to chronic hypoxia); and 3) despite
      causing hypertrophy of both ventricles, chronic exposure to combined hypoxic-cold
      did not induce significant metabolic remodeling. GENERAL SIGNIFICANCE: In
      response to environmental challenges, cardiac muscles 1) show distinct physical
      and metabolic remodeling, 2) respond to two stressors simultaneously but not
      additively, and 3) maintain an adult metabolic phenotype with long-term exposure
      to environmentally realistic hypoxic-cold.

PMID- 20801193
TI  - Connexins: sensors and regulators of cell cycling.
AB  - It is nowadays well established that gap junctions are critical gatekeepers of
      cell proliferation, by controlling the intercellular exchange of essential growth
      regulators. In recent years, however, it has become clear that the picture is not
      as simple as originally anticipated, as structural precursors of gap junctions
      can affect cell cycling by performing actions not related to gap junctional
      intercellular communication. Indeed, connexin hemichannels also foresee a pathway
      for cell growth communication, albeit between the intracellular compartment and
      the extracellular environment, while connexin proteins as such can directly or
      indirectly influence the production of cell cycle regulators independently of
      their channel activities. Furthermore, a novel set of connexin-like proteins, the
      pannexins, have lately joined in as regulators of the cell proliferation process,
      which they can affect as either single units or as channel entities. In the
      current paper, these multifaceted aspects of connexin-related signalling in cell
      cycling are reviewed.

PMID- 20801192
TI  - Hepcidin expression by human monocytes in response to adhesion and pro
      inflammatory cytokines.
AB  - BACKGROUND: A previous urine proteomic analysis from our laboratory suggested
      that hepcidin may be a biomarker for lupus nephritis flare. Immunohistochemical
      staining of kidney biopsies from lupus patients showed that hepcidin was
      expressed by infiltrating renal leukocytes. Here we investigated whether
      inflammatory cytokines relevant to the pathogenesis of lupus nephritis and other
      glomerular diseases regulate hepcidin expression by human monocytes. METHODS:
      Human CD14+ monocytes were incubated with interferon alpha (IFNalpha), interferon
      gamma (IFNgamma), interleukin-6 (IL6), interleukin-1 beta (IL1beta), monocyte
      chemotactic factor-1 (MCP1), or tumor necrosis factor alpha (TNFalpha). Hepcidin
      expression was examined by real-time PCR and enzyme immunoassay. RESULTS:
      Monocyte hepcidin mRNA increased during adherence to the tissue culture wells,
      reaching a level 150-fold higher than baseline within 12 h of plating. After
      accounting for the effects of adhesion, monocytes showed time and dose-dependent
      up-regulation of hepcidin mRNA upon treatment with IFNalpha or IL6. One hour of
      incubation with IFNalpha or IL6 increased hepcidin mRNA 20 and 80-fold,
      respectively; by 24 h the mRNA remained 5- and 2.4-fold higher than baseline.
      IL1beta, IFNgamma, and MCP-1 did not affect monocyte hepcidin expression.
      TNFalpha inhibited hepcidin induction by IL6 in monocytes by 44%. After 24 h of
      treatment with IFNalpha or IL6, immunoreactive hepcidin production by monocytes
      increased 3- and 2.6-fold, respectively. CONCLUSION: Human monocytes produce
      hepcidin in response to adhesion and the pro-inflammatory cytokines IFNalpha and
      IL6. GENERAL SIGNIFICANCE: The appearance of hepcidin in the kidneys or urine
      during glomerular diseases may be from infiltrating monocytes induced to express
      hepcidin by adherence and exposure to pro-inflammatory cytokines found in the
      renal milieu.

PMID- 20801195
TI  - Distribution and morphology of the catecholaminergic neural elements in the human
      hypothalamus.
AB  - Previous studies have demonstrated that catecholaminergic, tyrosine hydroxylase
      (TH)-immunoreactive (IR) perikarya and fibers are widely distributed in the human
      hypothalamus. Since TH is the key and rate-limiting enzyme for catecholaminergic
      synthesis, these IR neurons may represent dopaminergic, noradrenergic or
      adrenergic neural elements. However, the distribution and morphology of these
      neurotransmitter systems in the human hypothalamus is not entirely known. Since
      the different catecholaminergic systems can be detected by identifying the
      neurons containing the specific key enzymes of catecholaminergic synthesis, in
      the present study we mapped the catecholaminergic elements in the human
      hypothalamus using immunohistochemistry against the catecholaminergic enzymes,
      TH, dopamine beta-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase
      (PNMT). Only a few, PNMT-IR, adrenergic neuronal elements were found mainly in
      the infundibulum and the periventricular zone. DBH-IR structures were more widely
      distributed in the human hypothalamus occupying chiefly the
      infundibulum/infundibular nucleus, periventricular area, supraoptic and
      paraventricular nuclei. Dopaminergic elements were detected by utilizing double
      label immunohistochemistry. First, the DBH-IR elements were visualized; then the
      TH-IR structures, that lack DBH, were detected with a different chromogen. In our
      study, we conclude that all of the catecholaminergic perikarya and the majority
      of the catecholaminergic fibers represent dopaminergic neurons in the human
      hypothalamus. Due to the extremely small number of PNMT-IR, adrenergic structures
      in the human hypothalamus, the DBH-IR fibers represent almost exclusively
      noradrenergic neuronal processes. These findings suggest that the juxtapositions
      between the TH-IR and numerous peptidergic systems revealed by previous reports
      indicate mostly dopaminergic synapses.

PMID- 20801194
TI  - Complex role of zinc in methamphetamine toxicity in vitro.
AB  - Methamphetamine is a drug of abuse that can induce oxidative stress and
      neurotoxicity to dopaminergic neurons. We have previously reported that oxidative
      stress promotes the liberation of intracellular Zn(2+) from metal-binding
      proteins, which, in turn, can initiate neuronal injurious signaling processes.
      Here, we report that methamphetamine mobilizes Zn(2+) in catecholaminergic rat
      pheochromocytoma (PC12) cells, as measured by an increase in Zn(2+)-regulated
      gene expression driven by the metal response element transcription factor-1.
      Moreover, methamphetamine-liberated Zn(2+) was responsible for a pronounced
      enhancement in voltage-dependent K(+) currents in these cells, a process that
      normally accompanies Zn(2+)-dependent cell injury. Overnight exposure to
      methamphetamine induced PC12 cell death. This toxicity could be prevented by the
      cell-permeant zinc chelator N,N,N', N'-tetrakis(2-pyridylmethyl)-ethylenediamine
      (TPEN), and by over-expression of the Zn(2+)-binding protein metallothionein 3
      (MT3), but not by tricine, an extracellular Zn(2+) chelator. The toxicity of
      methamphetamine to PC12 cells was enhanced by the presence of co-cultured
      microglia. Remarkably, under these conditions, TPEN no longer protected but, in
      fact, dramatically exacerbated methamphetamine toxicity, tricine again being
      without effect. Over-expression of MT3 in PC12 cells did not mimic these toxicity
      enhancing actions of TPEN, suggesting that the chelator affected microglial
      function. Interestingly, P2X receptor antagonists reversed the toxicity-enhancing
      effect of TPEN. As such, endogenous levels of intracellular Zn(2+) may normally
      interfere with the activation of P2X channels in microglia. We conclude that
      Zn(2+) plays a significant but complex role in modulating the cellular response
      of PC12 cells to methamphetamine exposure in both the absence and presence of
      microglia.

PMID- 20801196
TI  - Aging effects on selective attention-related electroencephalographic patterns
      during face encoding.
AB  - Previous electrophysiological studies revealed that human faces elicit an early
      visual event-related potential (ERP) within the occipito-temporal cortex, the
      N170 component. Although face perception has been proposed to rely on automatic
      processing, the impact of selective attention on N170 remains controversial both
      in young and elderly individuals. Using early visual ERP and alpha power
      analysis, we assessed the influence of aging on selective attention to faces
      during delayed-recognition tasks for face and letter stimuli, examining 36
      elderly and 20 young adults with preserved cognition. Face recognition
      performance worsened with age. Aging induced a latency delay of the N1 component
      for faces and letters, as well as of the face N170 component. Contrasting with
      letters, ignored faces elicited larger N1 and N170 components than attended faces
      in both age groups. This counterintuitive attention effect on face processing
      persisted when scenes replaced letters. In contrast with young, elderly subjects
      failed to suppress irrelevant letters when attending faces. Whereas attended
      stimuli induced a parietal alpha band desynchronization within 300-1000 ms post
      stimulus with bilateral-to-right distribution for faces and left lateralization
      for letters, ignored and passively viewed stimuli elicited a central alpha
      synchronization larger on the right hemisphere. Aging delayed the latency of this
      alpha synchronization for both face and letter stimuli, and reduced its amplitude
      for ignored letters. These results suggest that due to their social relevance,
      human faces may cause paradoxical attention effects on early visual ERP
      components, but they still undergo classical top-down control as a function of
      endogenous selective attention. Aging does not affect the face bottom-up alerting
      mechanism but reduces the top-down suppression of distracting letters, possibly
      impinging upon face recognition, and more generally delays the top-down
      suppression of task-irrelevant information.

PMID- 20801197
TI  - Dopamine enhances the excitability of somatosensory thalamocortical neurons.
AB  - The thalamus conveys sensory information from peripheral and subcortical regions
      to the neocortex in a dynamic manner that can be influenced by several
      neuromodulators. Alterations in dopamine (DA) receptor function in thalami of
      Schizophrenic patients have recently been reported. In addition, schizophrenia is
      associated with sensory gating abnormalities and sleep-wake disturbances, thus we
      examined the role of DA on neuronal excitability in somatosensory thalamus. The
      ventrobasal (VB) thalamus receives dopaminergic innervation and expresses DA
      receptors; however, the action of DA on VB neurons is unknown. In the present
      study, we performed whole cell current- and voltage-clamp recordings in rat brain
      slices to investigate the role of DA on excitability of VB neurons. We found that
      DA increased action potential discharge and elicited membrane depolarization via
      activation of different receptor subtypes. Activation of D2-like receptors
      (D(2R)) leads to enhanced action potential discharge, whereas the membrane
      depolarization was mediated by D1-like receptors (D(1R)). The D(2R-mediated)
      increase in spike discharge was mimicked and occluded by alpha-dendrotoxin (alpha
      DTX), indicating the involvement of a slowly inactivating K(+) channels. The D1R
      mediated membrane depolarization was occluded by barium, suggesting the
      involvement of a G protein-coupled K(+) channel or an inwardly rectifying K(+)
      channel. Our results indicate that DA produces dual modulatory effects acting on
      subtypes of DA receptors in thalamocortical relay neurons, and likely plays a
      significant role in the modulation of sensory information.

PMID- 20801198
TI  - Abnormal 5-HT modulation of stress behaviors in the Kv4.2 knockout mouse.
AB  - The Kv4.2 gene codes for an essential subunit of voltage-gated A-type potassium
      channels that are involved in dendritic signal integration and synaptic
      plasticity. Detailed cellular characterization in CA1 pyramidal neurons of the
      hippocampus has shown that knocking out the Kv4.2 gene increases neuronal
      excitability and promotes long-term potentiation. However, the overall behavioral
      consequences of these modifications have not been fully explored. Given the
      growing connection between neuronal plasticity and affect processing in the
      hippocampus and other Kv4.2 expressing regions, we proposed to investigate
      whether the absence of this gene would alter the stress response of mice to the
      forced swimming and tail suspension tests (TSTs) for depression-like behavior.
      Kv4.2 knockout (KO) mice, generated in the 129SvEv background, demonstrated
      elevated immobility and a loss of swimming, as well as antidepressant resistance
      to the selective 5-HT reuptake inhibitor fluoxetine (FLX). Characterization of a
      relatively new head movement behavior category, responsive to serotonergic
      treatment in wildtype (WT) mice, supported conclusions of abnormal 5-HT
      modulation. Electrophysiology recordings in the prefrontal cortex showed a
      blunting of postsynaptic response to direct 5-HT application following a single
      period of swim stress only in the animals without the Kv4.2 subunit. Based on our
      findings, we hypothesize that Kv4.2 KO mice may have an exaggerated 5-HT response
      to stress leading to a premature desensitization of postsynaptic receptors and a
      loss of continued behavior modulation. These results may shed some light on the
      involvement of A-type potassium channels in the effective action of selective
      serotonin reuptake inhibitor (SSRI) antidepressants.

PMID- 20801199
TI  - Resurgence of derived stimulus relations: replication and extensions.
AB  - Resurgence typically refers to the recovery of a previously reinforced response
      when a more recently reinforced response is extinguished. Under conditions of
      punishment, Wilson and Hayes (1996) observed the recovery of derived stimulus
      relations that never had been correlated with differential consequences. The
      present study systematically replicated the findings of Wilson and Hayes by
      observing the recovery of derived stimulus relations under extinction conditions
      and with an additional equivalence class. College students received arbitrary
      matching-to-sample training in Phase 1 that resulted in four 4-member stimulus
      equivalence classes. These derived relations were not correlated with
      differential consequences. In Phase 2, with the same stimuli, the students
      received training that resulted in four different 4-member stimulus-equivalence
      classes. After the emergence and reinforcement of the latter derived relations,
      their extinction generated the recurrence of the derived relations from Phase 1.
      The implications of these findings for conceptualizing resurgence are discussed.

PMID- 20801200
TI  - Risperidone solid dispersion for orally disintegrating tablet: its formulation
      design and non-destructive methods of evaluation.
AB  - The focus of present investigation was to assess the utility of non-destructive
      techniques in the evaluation of risperidone solid dispersions (SD) with methyl
      beta-cyclodextrin (MBCD) and subsequent incorporation of the SD into orally
      disintegrating tablets (ODT) for a faster release of risperidone. The SD was
      prepared by a solvent evaporation method and evaluated by scanning electron
      microscopy (SEM), Fourier transform infrared (FTIR), near infrared spectroscopy
      (NIR), NIR-chemical imaging (NIR-CI), powder X-ray diffraction (PXRD) and
      differential scanning calorimetry (DSC). DSC and XRD analysis indicated that
      crystallinity of SD has reduced significantly. FTIR showed no interaction between
      risperidone and MBCD. Partial least square (PLS) was applied to the NIR data for
      the construction of chemometric models to determine both components of the SD.
      Good correlations were obtained for calibration and prediction as indicated by
      correlation coefficients >0.9965. The model was more accurate and less biased in
      predicting the MBCD than risperidone as indicated by its lower mean accuracy and
      mean bias values. SD-3 (risperidone:MBCD, 1:3) was incorporated into ODT tablets
      containing diluent (D-mannitol, FlowLac((r)) 100 or galenIQTM-721) and
      superdisintegrant (Kollidon((r)) CL-SF, Ac-Di-Sol or sodium starch glycolate).
      Disintegration time, T(50) and T(90) were decreased in the formulations
      containing mannitol and Kollidon((r)) CL-SF, but increased with galenIQTM-721 and
      sodium starch glycolate, respectively. NIR-CI images confirmed the homogeneity of
      SD and ODT formulations.

PMID- 20801201
TI  - Preparation and evaluation of nicotinic acid sustained-release pellets combined
      with immediate release simvastatin.
AB  - This study was performed to prepare high-dose nicotinic acid (NA) loaded
      sustained-release pellets coated with double polymer and simvastatin (SIM). The
      uncoated pellets were prepared by extrusion-spheronization and the double
      ethylcellucose (EC) films were coated in a bottom-spray fluidized bed coater. SIM
      was milled by wet grinding and then the milled suspension was layered on the
      coated pellets. Results showed that coated with 1.5% subcoating and 1% outer
      coating composed of EC and polyvinyl pyrrolidone K30 (PVP(K30)) in ratios of 5:1
      and 2:1, NA release behavior was very similar to the reference (NER/S; SIMCOR,
      Abbott) in different media. And SIM was delivered more rapidly than that of the
      reference, while the SIM layer had no influence on NA release. During 6-month
      storage at 40 degrees C/75% RH, the two drugs exhibited stable dissolution
      behavior. It was observed that the content uniformity of SIM was provided by the
      present preparation and SIM was stable if adding light magnesium oxide in the
      grinding procedure. Results indicated it was possible to prepare high-dose
      sustained-release NA pellets combined with little-dose immediate release SIM by
      spraying double EC polymer and SIM milled suspension on NA pellets in a bottom
      spray fluidized bed coater, respectively.

PMID- 20801202
TI  - Characterization and in vitro evaluation of freeze-dried microparticles composed
      of granisetron-cyclodextrin complex and carboxymethylcellulose for intranasal
      delivery.
AB  - The aim of this study was to prepare microparticles (MPs) of granisetron (GRN) in
      combination with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and sodium
      carboxymethylcellulose (CMC-Na) by the simple freeze-drying method for intranasal
      delivery. The composition of MPs was determined from the phase-solubility study
      of GRN in various CDs. Fourier transform infrared spectroscopy (FT-IR), powder X
      ray diffraction (PXRD) analysis and differential scanning calorimetry (DSC)
      studies were performed to evaluate possible interactions between GRN and
      excipients. The results indicated the formation of inclusion complex between GRN
      and CD, and the conversion of drug into amorphous state. The in vitro release of
      GRN from MPs was determined in phosphate buffered saline (pH 6.4) at 37 degrees
      C. Cytotoxicity of the MPs and in vitro permeation study were conducted by using
      primary human nasal epithelial (HNE) cells and their monolayer system cultured by
      air-liquid interface (ALI) method, respectively. The MPs showed significantly
      higher GRN release profile compared to pure GRN. Moreover, the prepared MPs
      showed significantly lower cytotoxicity and higher permeation profile than that
      of GRN powder (p<0.05). These results suggested that the MPs composed of GRN, HP
      beta-CD and CMC-Na represent a simple and new GRN intranasal delivery system as
      an alternative to the oral and intravenous administration of GRN.

PMID- 20801203
TI  - Novel pH-sensitive polyacetal-based block copolymers for controlled drug
      delivery.
AB  - The principal aim of this study was to synthesize and characterize pH-sensitive
      biodegradable triblock copolymers containing a hydrophobic polyacetal segment for
      controlled drug delivery. Poly(ethylene glycol)-poly(ethyl glyoxylate)
      poly(ethylene glycol) (PEG-PEtG-PEG) triblock copolymers with PEG molecular
      weights 500 (PEtG-PEG(500)) and 750 (PEtG-PEG(750)) were synthesized by PEtG end
      capping with methoxy PEG via a carbamate linkage. Synthesized amphiphilic PEG
      PEtG-PEG was characterized by (1)H NMR spectroscopy. Molecular weights of PEtG
      PEG(500) and PEtG-PEG(750) were determined to be 2823 and 3387, respectively, by
      gel permeation chromatography. The polymers with a biodegradable polyacetal block
      underwent pH-dependent degradation via an acid-catalyzed hydrolysis. Paclitaxel
      (PTX)-loaded polymeric micelles were prepared by a dialysis method and the amount
      of PTX incorporated into the polymeric micelle formulations was 45,000 times
      greater than the water solubility of PTX at room temperature. The polymeric
      micelles prepared from the amphiphilic PEG-PEtG-PEG triblock copolymers have
      released the loaded PTX in a pH-dependent manner. The novel PEtG-based
      amphiphilic block copolymers can find applications for targeted and controlled
      drug delivery to the acidic environments found in tumors and intracellular
      compartments.

PMID- 20801204
TI  - Improving the hardness of dry granulated tablets containing sodium lauryl
      sulfate.
AB  - The impact of the addition of a wetting agent, the surfactant sodium lauryl
      sulfate (SLS), on the tablet hardness of a dry granulated, solid oral dosage form
      was investigated. In three batches, SLS was added concurrently with: (1) a poorly
      soluble, highly hydrophobic active pharmaceutical ingredient (API) and the other
      excipients prior to the initial blending step, (2) magnesium stearate prior to
      roller compaction, or (3) magnesium stearate prior to tableting. A fourth batch,
      which did not contain SLS, served as a control. The maximum hardness of 100 mg,
      1/4"-SRC tablets for the four batches--SLS added initially, prior to roller
      compaction, prior to tableting, and no SLS--were 61+/-3, 71+/-3, 89+/-5, and 86+/
      3N, respectively, suggesting reduced processing of SLS improves tablet hardness
      by ~50%. Dissolution of the tablets in 900 ml of simulated gastric fluid with
      paddles at 75 rpm showed that: (1) there was no impact on the insertion point of
      SLS into the process on API dissolution, and (2) that the presence of SLS
      improved dissolution by 5% compared to the control tablets. Adding SLS just prior
      to tableting can improve tablet hardness and yield similar dissolution
      performance relative to SLS addition prior to the initial blending step.

PMID- 20801205
TI  - Evaluation of cationic nanoparticles of biodegradable copolymers as siRNA
      delivery system for hepatitis B treatment.
AB  - Cationic nanoparticles of biodegradable polymers such as poly (lactide) (PLA)
      have been shown to be promising carrier systems for DNA and siRNA delivery.
      However, the parameters which influence the transfection efficiency have not been
      investigated in details. In this work, four groups of cationic PLA-based
      nanoparticles were synthesized by the nanoprecipitation method and solvent
      evaporation method with polyethyleneimine (PEI) and chitosan as two types of
      surface coating materials. Cationic poly (D,L-lactide-co-glycolide) (PLGA)-PEI,
      PLGA-chitosan and methoxy poly (ethylene glycol)-poly (lactide) (mPEG)-PLA/PEI,
      mPEG-PLA-chitosan nanoparticles were characterized in terms of size and size
      distribution by laser scattering, surface charge by zeta potential measurement,
      and surface chemistry by X-ray electron spectroscopy (XPS). The four type pg
      nanoparticles were compared for their interaction with siRNA and nanoparticles
      mediated siRNA transfection efficiency with a hepatitis B model, where the
      inhibition effects of the double strand RNA (dsRNA) mediated by the four types of
      nanoparticles were evaluated by measuring the HBsAg expression level. The highest
      inhibition effect of HBsAg (the surface antigen of the hepatitis B Virus (HBV),
      which indicates current hepatitis B infection) expression was achieved by the
      mPEG-PLA-PEI nanoparticles mediated siRNA transfection. The results demonstrated
      that the siRNA delivery follows a size and surface charge dependant manner.

PMID- 20801206
TI  - Errors in measurement of three-dimensional motions of the stapes using a laser
      Doppler vibrometer system.
AB  - Previous studies have suggested complex modes of physiological stapes motions
      based upon various measurements. The goal of this study was to analyze the
      detailed errors in measurement of the complex stapes motions using laser Doppler
      vibrometer (LDV) systems, which are highly sensitive to the stimulation intensity
      and the exact angulations of the stapes. Stapes motions were measured with
      acoustic stimuli as well as mechanical stimuli using a custom-made three-axis
      piezoelectric actuator, and errors in the motion components were analyzed. The
      ratio of error in each motion component was reduced by increasing the magnitude
      of the stimuli, but the improvement was limited when the motion component was
      small relative to other components. This problem was solved with an improved
      reflectivity on the measurement surface. Errors in estimating the position of the
      stapes also caused errors on the coordinates of the measurement points and the
      laser beam direction relative to the stapes footplate, thus producing errors in
      the 3-D motion components. This effect was small when the position error of the
      stapes footplate did not exceed 5 degrees.

PMID- 20801207
TI  - The genus Stephania (Menispermaceae): chemical and pharmacological perspectives.
AB  - The plants of the genus Stephania (Menispermaceae) are widely distributed, and
      have long been used in folk medicine for the treatment of various ailments such
      as asthma, tuberculosis, dysentery, hyperglycemia, malaria, cancer and fever.
      Over 150 alkaloids together with flavonoids, lignans, steroids, terpenoids and
      coumarins have been identified in the genus, and many of these have been
      evaluated for biological activity. This review presents comprehensive information
      on the chemistry and pharmacology of the genus together with the traditional uses
      of many of its plants. In addition, this review discusses the structure-activity
      relationship of different compounds as well as recent developments and the scope
      for future research in this aspect.

PMID- 20801208
TI  - Serum N-glycan profile shift during human ageing.
AB  - Biomarkers indicating biological age are of significant interest for prevention,
      diagnosis and monitoring (and the treatment) of age-related diseases. We
      previously reported an alteration of serum N-glycan profile in old humans using
      "DNA Sequencer Adapted-Fluorophore Assisted Carbohydrate Electrophoresis" (DSA
      FACE). To validate the shift in serum N-glycan profile during ageing, we studied
      serum N-glycan profiles in different age groups of healthy volunteers, patients
      with dementia, and patients with Cockayne syndrome, a genetic DNA repair disorder
      involving neurodegeneration and premature ageing. We found that the log of the
      ratio of two glycans (NGA2F and NA2F), named GlycoAgeTest, remained steady up to
      the age of 40years and thereafter gradually increased to reach its highest level
      in nonagenarians. Patients with dementia or Cockayne syndrome had a higher
      GlycoAgeTest level than age-matched healthy individuals. We thus demonstrate that
      the value of GlycoAgeTest is better than chronological age for estimating the
      physiological age of a human individual, and that it could be used as an ageing
      biomarker for healthy humans. Our data indicate that the GlycoAgeTest could be
      used as a non-invasive surrogate marker for general health, for forecasting
      disease progression during ageing, and for monitoring the efficacy of anti-ageing
      food compounds.

PMID- 20801209
TI  - Endotoxin and polycyclic aromatic hydrocarbons in ambient fine particulate matter
      from Fresno, California initiate human monocyte inflammatory responses mediated
      by reactive oxygen species.
AB  - In urban areas, a correlation between exposure to particulate matter (PM) from
      air pollution and increased cardiovascular morbidity and mortality has been
      observed. Components of PM include bacterial contaminants, transition metals,
      salts, polycyclic aromatic hydrocarbons (PAH), and carbonaceous material, which
      could interact with various cell types to produce systemic responses when
      inhaled. We examined the effects of PM collected from Fresno, California on
      activation of human monocytes and their interaction with vascular endothelium, a
      key event in atherogenesis. PM exposure increased cytokine expression and
      secretion from monocytes and enhanced monocyte adhesion to human aortic
      endothelial cells, both of which were attenuated by neutralizing endotoxin. PM
      also increased monocyte CYP1a1 expression, and inhibition of the aryl hydrocarbon
      receptor reduced the CYP1a1 and inflammatory responses. PM-treated monocytes
      accumulated intracellular reactive oxygen species (ROS), and antioxidants
      attenuated inflammatory and xenobiotic responses. Finally, supernatants from PM
      treated pulmonary microvascular endothelial cells induced monocyte inflammatory
      responses that were not a consequence of endotoxin transfer. These results
      suggest that certain components of urban PM, namely endotoxin and PAH, activate
      circulating monocytes directly or indirectly by first stimulating other cells
      such as pulmonary endothelial cells, providing several mechanisms by which PM
      inhalation could induce pulmonary and/or systemic inflammation.

PMID- 20801210
TI  - Genome-wide analysis of hepatic gene silencing in mammalian cell hybrids.
AB  - Silencing of tissue-specific gene expression in mammalian somatic cell hybrids is
      a well-documented epigenetic phenomenon which is both profound (involving a large
      number of genes) and enigmatic. Our aim was to utilize whole-genome microarray
      analyses to determine the true extent of gene silencing on a genomic level. By
      comparing gene expression profiles of hepatoma*fibroblast cell hybrids with those
      of parental cells, we have identified over 300 liver-enriched genes that are
      repressed at least 5-fold in the cell hybrids, the majority of which are
      repressed at least 10-fold. Also, we identify nearly 200 fibroblast-enriched
      genes that are repressed at least 5-fold. Silenced hepatic genes include several
      that encode transcription factors and proteins involved in signal transduction
      pathways. These data suggest that extensive reprogramming occurs in cell hybrids,
      leading to a nearly global (although not complete) loss of tissue-specific gene
      expression.

PMID- 20801211
TI  - A reinvestigation of the reaction of coumarins with superoxide in the liposomal
      bilayer: correlation between depth and reactivity.
AB  - Afri et al. reported in this journal (Free Radic. Biol. Med.32:605-618; 2002)
      that a direct relationship exists between the depth of alkanoylcoumarins 1 within
      the liposomal lipid bilayer and the rate at which they undergo superoxide
      mediated saponification. These results were based on a correlation between the
      (13)C NMR chemical shift of polarizable carbonyl carbons and the E(T)(30)
      polarity they sense. Subsequent studies challenged these results, however,
      demonstrating that, in conjugated ketones and aldehydes, charge separation
      influences the E(T)(30) polarity measured. To elucidate whether this is true for
      conjugated esters such as coumarins as well, the nonconjugated analogs 3,4
      dihydrocoumarins 11 and 15 were intercalated within DMPC liposomal bilayers and
      their relative locations within the liposomal bilayer were determined. The length
      of the alkyl chain substituted at C-4 and C-10 influences the depth of the
      substrates within the liposome. The location of these 3,4-dihydrocoumarins
      corresponds well with the conjugated analog coumarin 1-confirming the validity of
      the abovementioned results of Afri et al. The lack of substantial charge
      separation in the coumarin 1 system presumably results from the "swamping-out"
      effect of the ester oxygen. Instead of 1,3-delocalization of charge, typical of
      conjugated systems, delocalization of the nonbonding pair on the ester oxygen
      predominates.

PMID- 20801212
TI  - H2O2-induced mitochondrial fragmentation in C2C12 myocytes.
AB  - In skeletal muscle and many other cell types, mitochondria exist as an elaborate
      and dynamic network in which "individual" mitochondria exist only transiently
      even under nonstimulated conditions. The balance of continuous mitochondrial
      fission and fusion defines the morphology of the mitochondrial reticulum.
      Environmental stimuli, such as oxidative stress, can influence fusion and fission
      rates, resulting in a transformation of the network's connectivity. Using
      confocal laser scanning microscopy of C(2)C(12) mouse myocytes, we show that
      acute exposure to the reactive oxygen species (ROS) hydrogen peroxide (H(2)O(2))
      induces a slow fragmentation of the mitochondrial reticulum that is reversible
      over 24h. Although H(2)O(2) decomposes rapidly in culture medium, the full extent
      of fragmentation occurs 5-6h posttreatment, suggesting that H(2)O(2) affects
      mitochondrial morphology by modulating cellular physiology. Supraphysiological
      (>1 mM) concentrations of H(2)O(2) are cytotoxic, but lower concentrations (250
      MUM) sufficient to induce transient fragmentation do not lower cell viability.
      H(2)O(2)-induced mitochondrial fragmentation is preceded by decreases in inner
      mitochondrial membrane potential and maximal respiratory rate, suggesting a
      possible mechanism. Because H(2)O(2) is produced in contracting muscle, our
      results raise the possibility that ROS generation may contribute to exercise
      induced changes in mitochondrial morphology in vivo.

PMID- 20801214
TI  - Ppm1E is an in cellulo AMP-activated protein kinase phosphatase.
AB  - Activation of 5'-AMP-activated protein kinase (AMPK) is believed to be the
      mechanism by which the pharmaceuticals, metformin and phenformin, exert their
      beneficial effects for treatment of type 2 diabetes. These biguanide drugs
      elevate 5'-AMP, which allosterically activates AMPK and promotes phosphorylation
      on Thr172 of AMPK catalytic alpha subunits. Although kinases phosphorylating this
      site have been identified, phosphatases that dephosphorylate it are unknown. The
      aim of this study is to identify protein phosphatase(s) that dephosphorylate
      AMPKalpha-Thr172 within cells. Our initial data indicated that members of the
      protein phosphatase Mg/Mn(2+)-dependent [corrected] (PPM) family and not those of
      the PPP family of protein serine/threonine phosphatases may be directly or
      indirectly inhibited by phenformin. Using antibodies raised to individual Ppm
      phosphatases that facilitated the assessment of their activities, phenformin
      stimulation of cells was found to decrease the Mg(2+)/Mn(2+)-dependent
      [corrected] protein serine/threonine phosphatase activity of Ppm1E and Ppm1F, but
      not that attributable to other PPM family members, including Ppm1A/PP2Calpha.
      Depletion of Ppm1E, but not Ppm1A, using lentiviral-mediated stable gene
      silencing, increased AMPKalpha-Thr172 phosphorylation approximately three fold in
      HEK293 cells. In addition, incubation of cells with low concentrations of
      phenformin and depletion of Ppm1E increased AMPK phosphorylation synergistically.
      Ppm1E and the closely related Ppm1F interact weakly with AMPK and assays with
      lysates of cells stably depleted of Ppm1F suggest [corrected] that this
      phosphatase contributes to dephosphorylation of AMPK. The data indicate that
      Ppm1E and probably PpM1F are in cellulo AMPK phosphatases and that Ppm1E is a
      potential anti-diabetic drug target.

PMID- 20801215
TI  - Ultrasound assisted cocrystallization from solution (USSC) containing a non
      congruently soluble cocrystal component pair: Caffeine/maleic acid.
AB  - Ultrasound assisted solution cocrystallization (USSC) has been studied using a
      non-congruently soluble pair of caffeine and maleic acid in methanol. USSC was
      compared with solvent cooling and slurry sonication using different molar ratios
      of caffeine:maleic acid (1:0.5, 1:1, 1:2, 1:3 and 1:3.5) in solution/slurry.
      Products were characterized by PXRD and Raman spectroscopy techniques. In USSC
      trials, the content of cocrystal in the product was observed to increase with
      increase in amount of maleic acid in solution. Only USSC offered pure
      caffeine/maleic acid 2:1 cocrystal product when caffeine:maleic acid; 1:3.5 molar
      ratio was taken in solution. Caffeine/maleic acid 1:1 cocrystal and maleic acid
      were not obtained in neither of the techniques. Products of solvent cooling and
      slurry sonication experiments were mixtures of caffeine and caffeine/maleic acid
      2:1 cocrystal in varying amounts. In USSC, ultrasound application must have
      attained simultaneous supersaturation of cocrystal components in solution due to
      altered supersaturation conditions resulting in cocrystal formation. For this
      simultaneous attainment of supersaturation, molar ratio of cocrystal components
      in solution was identified as an important parameter while designing experiments
      for a non-congruently soluble pair having large solubility difference.

PMID- 20801213
TI  - Ferricytochrome c protects mitochondrial cytochrome c oxidase against hydrogen
      peroxide-induced oxidative damage.
AB  - An excess of ferricytochrome c protects purified mitochondrial cytochrome c
      oxidase and bound cardiolipin from hydrogen peroxide-induced oxidative
      modification. All of the peroxide-induced changes within cytochrome c oxidase,
      such as oxidation of Trp(19,IV) and Trp(48,VIIc), partial dissociation of
      subunits VIa and VIIa, and generation of cardiolipin hydroperoxide, no longer
      take place in the presence of ferricytochrome c. Furthermore, ferricytochrome c
      suppresses the yield of H(2)O(2)-induced free radical detectable by electron
      paramagnetic resonance spectroscopy within cytochrome c oxidase. These protective
      effects are based on two mechanisms. The first involves the peroxidase/catalase
      like activity of ferricytochrome c, which results in the decomposition of
      H(2)O(2), with the apparent bimolecular rate constant of 5.1+/-1.0M(-1)s(-1).
      Although this value is lower than the rate constant of a specialized peroxidase,
      the activity is sufficient to eliminate H(2)O(2)-induced damage to cytochrome c
      oxidase in the presence of an excess of ferricytochrome c. The second mechanism
      involves ferricytochrome c-induced quenching of free radicals generated within
      cytochrome c oxidase. These results suggest that ferricytochrome c may have an
      important role in protection of cytochrome c oxidase and consequently the
      mitochondrion against oxidative damage.

PMID- 20801216
TI  - Elucidation of the internal physical and chemical microstructure of
      pharmaceutical granules using X-ray micro-computed tomography, Raman microscopy
      and infrared spectroscopy.
AB  - X-ray micro-computed tomography (XMCT) was used in conjunction with confocal
      Raman mapping to measure the intra-granular pore size, binder volumes and to
      provide spatial and chemical maps of internal granular components in alpha
      lactose monohydrate granules formulated with different molecular weights of
      polyvinyl pyrrolidone (PVP). Infrared spectroscopy was used to understand the
      molecular association of binder domains. Granules were prepared by high-shear
      aqueous granulation from alpha-lactose monohydrate and PVP K29/32 or K90. XMCT
      was used to visualise the granule microstructure, intra-granular binder
      distribution and measure intra-granular porosity, which was subsequently related
      to intrusion porosimetry measurements. Confocal Raman microscopy and infrared
      microscopy were employed to investigate the distribution of components within the
      granule and explore the nature of binder substrate interactions. XMCT data sets
      of internal granule microstructure provided values of residual porosity in the
      lactose:PVP K29/32 and lactose:PVP K90 granules of 32.41 +/- 4.60% and 22.40 +/-
      0.03%, respectively. The binder volumes of the lactose:PVP K29/32 and lactose:PVP
      K90 granules were 2.98 +/- 0.10% and 3.38 +/- 0.07%, respectively, and were
      attributed to PVP-rich binder domains within the granule. Confocal Raman
      microscopy revealed anisotropic domains of PVP between 2 MUm and 20 MUm in size
      surrounded by larger particles of lactose, in both granule types. Raman data
      showed that PVP domains contained various amounts of lactose, whilst IR
      microscopy determined that the PVP was molecularly associated with lactose,
      rather than residual water. The work shows that XMCT can be applied to
      investigate granular microstructure and resolve the porosity and the excipient
      and binder volumes. Combining this technique with vibrational techniques provides
      further structural information and aids the interpretations of the XMCT images.
      When used complementarily, these techniques highlighted that porosity and binder
      volume were the most significant microstructural differences between the alpha
      lactose monohydrate granules formulated with the different grades of PVP.

PMID- 20801217
TI  - The impact of CD4+Foxp3+ Treg on immunity to murine cytomegalovirus after bone
      marrow transplantation depends on the peripheral or thymic source of T cell
      regeneration.
AB  - OBJECTIVE: The adoptive transfer of regulatory T cells (Treg) in murine models
      has been shown to ameliorate graft-versus-host disease while it may preserve the
      graft-versus-leukemia effect. However, the impact of Treg on infectious immunity
      after bone marrow transplantation (BMT) is still unclear. Immunocompetence
      against opportunistic viral infections depends on the kinetics of T cell recovery
      after BMT through two distinctive processes, i.e. lymphopenia-induced
      proliferation (LIP) of mature T cells and generation of T cells through
      thymopoiesis. METHODS: In this study, we set out to assess the effects of
      adoptively transferred Treg on T cell regeneration in a homeostatic peripheral T
      cell expansion model and a thymopoiesis-dependent BMT model, and on murine
      cytomegalovirus (mCMV) clearance and mortality following mCMV challenge. RESULTS:
      Using lymphopenic Rag-2(-/-)gammac(-/-) mice that received a limited number of
      congenic T cells, we demonstrate that adoptively transferred Treg abrogate LIP of
      T cells. mCMV challenge resulted in a rapid increase of viral load and death in
      mice that received Treg, but not in controls. In contrast, following syngeneic T
      cell-depleted BMT in Rag-2(-/-)gammac(-/-) mice, adoptively transferred Treg did
      not delay T cell reconstitution nor suppressed thymic output and had no effect on
      viral clearance and survival following mCMV-challenge. CONCLUSION: The effect of
      Treg on T cell-mediated immunocompetence against mCMV early after BMT depends on
      the relative contribution of peripheral expansion and thymopoiesis to T cell
      regeneration.

PMID- 20801218
TI  - CREB signalling regulates early survival, neuronal gene expression and
      morphological development in adult subventricular zone neurogenesis.
AB  - Neural stem cells in the subventricular zone (SVZ) of the lateral ventricles give
      rise to new interneurons of the olfactory bulb (OB) throughout life. SVZ/OB
      neurogenesis is influenced by olfactory network activity, which modulates the
      survival of new neurons during their integration into the OB network. Previous
      work suggested that such activity-dependent survival is regulated via the CREB
      signalling pathway. Curiously, CREB signalling is already active during the early
      developmental stages of adult SVZ/OB neurogenesis. To investigate the role of
      cell autonomous CREB signalling during early stages of adult SVZ/OB neurogenesis,
      we ablated CREB-pathway activity in the SVZ/OB neurogenic lineage using a
      retroviral strategy. Surprisingly, loss of CREB signalling resulted in increased
      cell death and loss of expression of the neurogenic transcription factor Pax 6,
      and of a subset of neuronal proteins in migrating neurons of the RMS. Moreover,
      post-migratory neurons in the OB displayed impaired dendritic development. These
      results demonstrate an essential role for CREB signalling in maturation of
      newborn neurons in the OB and uncover a novel role for CREB signalling in the
      survival and maintenance of neuronal gene expression during the early stages of
      SVZ/OB neurogenesis.

PMID- 20801219
TI  - Full length TrkB potentiates estrogen receptor alpha mediated transcription
      suggesting convergence of susceptibility pathways in schizophrenia.
AB  - In this study, we determined if estrogen receptor alpha (ERalpha) can interact
      with the full length tropomyosin receptor kinase B (TrkB-TK+), both of which are
      implicated in schizophrenia pathogenesis. Using neuronal (SHSY5Y) and non
      neuronal (CHOK1) cell-lines, we showed that TrkB-TK+ can increase transcription
      at estrogen response elements (EREs) with and without exogenous estrogen
      treatment. In the presence of estrogen, TrkB-TK+ further potentiated the effect
      of estrogen stimulation on ERalpha-mediated transcription. This synergistic
      effect of TrkB-TK+ on ERalpha-mediated transcription was not due to direct
      effects of TrkB-TK+ in the nucleus, but occurred through cytoplasmic signaling of
      TrkB-TK+ via the MAPK/ERK pathway to phosphorylate ERalpha, leading to an
      induction in ERalpha-mediated transcription. When we examined the PI3K/AKT
      pathway, we found that PI3K/AKT activity constitutively inhibited baseline
      transcription at EREs. Furthermore, we showed that signaling via PI3K/AKT
      inhibited TrkB-TK+-dependent transcriptional potentiation at EREs. Our findings
      suggest that TrkB-TK+-linked second messenger signaling pathways can reciprocally
      regulate ERalpha-mediated transcription at EREs. Considering that both ERalpha
      and TrkB-TK+ expression are reduced in schizophrenia, our findings suggest that
      dysfunction in TrkB-TK+ signaling may occur upstream of, or in conjunction with a
      dysfunction in ERalpha, and that transcriptional regulation by ERalpha may be
      decreased by reductions in TrkB-TK+.

PMID- 20801220
TI  - Neurostatin blocks glioma cell cycle progression by inhibiting EGFR activation.
AB  - The high frequency and malignancy of human glioblastomas has stimulated the
      search for potential therapeutic approaches. The control of the glioma cell
      proliferation in response to mitogenic signals is one of the most promising
      antitumoral strategies, and the main target of several therapies. Neurostatin, an
      O-acetylated derivative of the ganglioside GD1b, has potent antiproliferative
      activity over the in vitro and in vivo growth of glioma cells. The mechanism of
      its antitumoral action is the focus of the present study. Using a combined in
      vitro-in vivo approach, we observed that neurostatin arrested glioma
      proliferation by inhibiting the expression of cell cycle promoters (i.e. cyclins
      and CDKs) and promoting the expression of cell cycle inhibitors (i.e. p21 and
      p27). Neurostatin inhibits epidermal growth factor receptor (EGFR) signaling
      pathways, blocking the activation of the main promitogenic MAPKs and PI3K
      pathways. Neurostatin action not only interferes in the cell cycle progression,
      but also in the protection from apoptosis, and the generation of angiogenic and
      invasive responses. The antitumoral actions described here point to neurostatin
      as a novel and promising chemotherapeutic agent for glioma treatment.

PMID- 20801221
TI  - The use of immunohistochemistry to determine oncolytic reovirus distribution and
      replication in-human tumors.
AB  - An oncolytic virus is considered a targeted cancer therapy due to its ability to
      specifically target, replicate in and lyse cancer cells while leaving normal
      cells unharmed. Over the last few years several tumor selective oncolytic viruses
      have been developed. These include certain DNA viruses such as adenovirus that
      have been genetically manipulated to target specific cancer cells by exerting
      restrictions on the virus at the level of cell entry, viral gene transcription
      and viral protein translation. There are a variety of RNA viruses being studied
      as possible cancer therapies including reovirus. Reovirus is intrinsically
      oncolytic without the need for any genetic manipulation. The inherent oncolytic
      properties of this virus are derived from the fact that it specifically targets
      cells with an activated Ras pathway found in many cancer cells. REOLYSIN(r) is a
      proprietary formulation of human reovirus type 3 Dearing developed by Oncolytics
      Biotech Inc. and is the only therapeutic reovirus in clinical development. This
      review provides an overview of the development of REOLYSIN as a potential cancer
      therapeutic and the growing role of in situ based molecular pathology methods in
      providing clinical proof of concept and in guiding clinical development.

PMID- 20801223
TI  - Microbial manipulations to improve fish health and production--a Mediterranean
      perspective.
AB  - The interactions between the endogenous gut microbiota and the fish host are
      integral in mediating the development, maintenance and effective functionality of
      the intestinal mucosa and gut associated lymphoid tissues (GALTs). These
      microbial populations also provide a level of protection against pathogenic
      visitors to the gastrointestinal (GI) tract and aid host digestive function via
      the production of exogenous digestive enzymes and vitamins. Manipulation of these
      endogenous populations may provide an alternative method to antibiotics to
      control disease and promote health management. Applications of probiotics for
      Mediterranean teleosts can stimulate immune responses, enhance growth
      performance, feed utilisation, digestive enzyme activities, antioxidant enzyme
      activities, gene expression, disease resistance, larval survival, gut morphology,
      modulate GI microbiota and mediate stress responses. Although considerably less
      information is available regarding prebiotic applications for Mediterranean
      teleosts, prebiotics also offer benefits with regards to improving immune status
      and fish production. Despite the promising potential benefits demonstrated in
      current literature, obtaining consistent and reliable results is often difficult
      due to our incomplete understanding of indigenous fish GI microbiota and their
      subsequent host interactions which mediate and drive both localised and systemic
      host immunological responses. Additionally, the probiotic and prebiotic (biotics)
      mechanisms which mediate host benefits at the mucosal interface are poorly
      understood. Future studies focused on these interactions utilising gnotobiotic
      techniques should provide a better understanding of how to extract the full
      potential of biotic applications to promote immune function of Mediterranean
      teleosts.

PMID- 20801224
TI  - The evolution of autodigestion in the mushroom family Psathyrellaceae
      (Agaricales) inferred from Maximum Likelihood and Bayesian methods.
AB  - Recently developed comparative phylogenetic methods offer a wide spectrum of
      applications in evolutionary biology, although it is generally accepted that
      their statistical properties are incompletely known. Here, we examine and compare
      the statistical power of the ML and Bayesian methods with regard to selection of
      best-fit models of fruiting-body evolution and hypothesis testing of ancestral
      states on a real-life data set of a physiological trait (autodigestion) in the
      family Psathyrellaceae. Our phylogenies are based on the first multigene data set
      generated for the family. Two different coding regimes (binary and multistate)
      and two data sets differing in taxon sampling density are examined. The Bayesian
      method outperformed Maximum Likelihood with regard to statistical power in all
      analyses. This is particularly evident if the signal in the data is weak, i.e. in
      cases when the ML approach does not provide support to choose among competing
      hypotheses. Results based on binary and multistate coding differed only modestly,
      although it was evident that multistate analyses were less conclusive in all
      cases. It seems that increased taxon sampling density has favourable effects on
      inference of ancestral states, while model parameters are influenced to a smaller
      extent. The model best fitting our data implies that the rate of losses of
      deliquescence equals zero, although model selection in ML does not provide proper
      support to reject three of the four candidate models. The results also support
      the hypothesis that non-deliquescence (lack of autodigestion) has been ancestral
      in Psathyrellaceae, and that deliquescent fruiting bodies represent the preferred
      state, having evolved independently several times during evolution.

PMID- 20801225
TI  - Genetic variation and phylogeny of the cosmopolitan marine genus Tubificoides
      (Annelida: Clitellata: Naididae: Tubificinae).
AB  - Prior attempts to resolve the phylogenetic relationships of the cosmopolitan,
      marine clitellate genus Tubificoides, using only morphology, resulted in
      unresolved trees. In this study, three mitochondrial and three nuclear loci (5912
      aligned sites) were analyzed, representing 14 morphologically separate species.
      Genetic distances within and between these forms on the basis of the
      mitochondrial genes (COI, 16S and 12S) revealed that 18 distinct mitochondrial
      lineages were represented in the data set. After analyzing also nuclear data
      (28S, 18S and ITS) we conclude that 17 separately evolving lineages (i.e.,
      phylogenetic species) were represented, including three new, cryptic species
      closely related to T. pseudogaster, T. amplivasatus and T. insularis,
      respectively. Special emphasis was put on the DNA barcoding gene (COI), which was
      subject to haplotype diversity analysis and, for four species, diagnostic
      position (as determined by the Characteristic Attribute Organization System
      [CAOS]) screening. Typically, the intralineage variation was 1-2 orders of
      magnitude smaller than the interlineage divergence, making COI useful for
      identification of species within Tubificoides. The genetic data corroborate that
      many of the morphospecies are coherent but widely distributed metapopulations.
      Monophyly of the genus is supported and the evolutionary history of parts of the
      genus is revealed by phylogenetic analysis of the combined data set. A northern
      hemisphere origin of the genus is suggested, and most of the widely distributed
      species are members of one particular clade. Two morphological characters
      previously emphasized in Tubificoides taxonomy (hair chaetae and cuticular
      papillation) were optimized on the phylogenetic tree, revealing considerable
      homoplasy, belying the utility of these features as phylogenetic markers.

PMID- 20801227
TI  - Thermodynamics guided lead discovery and optimization.
AB  - The documented unfavorable changes of physicochemical properties during lead
      discovery and optimization prompted us to investigate the present practice of
      medicinal chemistry optimization from a thermodynamic perspective. Basic
      principles of binding thermodynamics suggest that discriminating between enthalpy
      driven and entropy-driven optimizations could be beneficial. We hypothesize that
      entropy-driven optimizations might be responsible for the undesirable trend
      observed in physicochemical properties. Consequently, we suggest that enthalpy
      driven optimizations are preferred because they provide better quality compounds.
      Monitoring binding thermodynamics during optimization programs initiated from
      thermodynamically characterized hits or leads, therefore, could improve the
      success of discovery programs. Here, we summarize common industry practices for
      tackling optimization challenges and review how the assessment of binding
      thermodynamics could support medicinal chemistry efforts.

PMID- 20801228
TI  - L-DOPA-induced dyskinesia in Parkinson's disease: a drug discovery perspective.
AB  - L-DOPA-induced dyskinesia is a debilitating, treatment-limiting adverse effect
      that eventually occurs in the majority of Parkinson's disease patients. This
      review describes the strategy of biological testing, focusing on in vivo proof-of
      concept animal models. We distinguish between symptomatic efficacy markers in
      predictive preclinical in vivo models and confounding factors that eventually
      produce false positive results. Clinical studies and predicted efficacy from
      preclinical studies are recapitulated and insights into the attempt to bridge
      preclinical and clinical studies are given. Furthermore, the mode of action that
      is to be involved in emerging therapy against L-DOPA-induced dyskinesia is
      reviewed.

PMID- 20801226
TI  - Ciliary blood flow and aqueous humor production.
AB  - Aqueous humor production is a metabolically active process sustained by the
      delivery of oxygen and nutrients and removal of metabolic waste by the ciliary
      circulation. This article describes our investigations into the relationship
      between ciliary blood flow and aqueous humor production. The results presented
      indicate that there is a dynamic relationship between ciliary blood flow and
      aqueous humor production, with production being blood flow independent above a
      critical level of perfusion, and blood flow dependent below it. The results also
      show that the plateau portion of the relationship shifts up or down depending on
      the level of secretory stimulation or inhibition, and that oxygen is one critical
      factor provided by ciliary blood flow. Also presented is a theoretical model of
      ocular hydrodynamics incorporating these new findings.

PMID- 20801222
TI  - Identification of immune genes of the miiuy croaker (Miichthys miiuy) by
      sequencing and bioinformatic analysis of ESTs.
AB  - Miiuy croaker (Miichthys miiuy) is an economically important fish in China.
      However, genomic research on this species is still in its infancy, and genomic
      resources are largely unavailable. In order to isolate functional genes involved
      in immunity, a normalized cDNA library was constructed from the spleen of the
      miiuy croaker. A total of 5053 ESTs from the library were sequenced and compared
      with sequences in the GenBank database. The 4609 high-quality ESTs were assembled
      into 3221 unigenes. Based on sequence similarities, 193 immune genes were
      identified such as major histocompatibility complex, cytokines and cytokine
      receptors, adhesive proteins, stress proteins, transcription factors for immune
      response, immunoglobulin and coagulation factors. Our study thus provides both a
      detailed annotation of immune genes in miiuy croaker and a collection of novel
      transcripts of Fc receptor-like 5 in teleost for the first time.

PMID- 20801229
TI  - Fragment-based approaches and the prospect of fragmented prodrugs.

PMID- 20801230
TI  - Chromosomal aberration in the post-implantation embryos sired by tamoxifen
      treated male rats.
AB  - Tamoxifen is a synthetic non-steroidal Selective Estrogen Receptor Modulator used
      in the treatment of breast cancer and in treatment of male fertility. Earlier
      studies from our laboratory had demonstrated an increase in post-implantation
      embryo loss following tamoxifen treatment to adult male rats at a dose of
      0.4mg/kg/day for 60 days. The post-implantation loss occurred at around 9-10 days
      of gestation suggesting that paternal factors involved in embryo development were
      affected by tamoxifen treatment. The present study was done to determine if any
      chromosomal aberrations occurred in the embryos sired by tamoxifen treated male
      rats. Chromosomal aberrations induced by tamoxifen treatment to adult male rats
      in the bone marrow (F(0) males) and in the embryos sired by these males (F(1)
      progeny) were determined. In addition, the reproductive performance of the F(1)
      progeny was assessed. A significant dose dependent reduction in mitotic activity
      in the bone marrow and embryonic cells was observed after tamoxifen treatment. In
      addition, tamoxifen also induced a significant dose dependent increase in the
      frequency of chromosomal aberrations, mainly gaps and breaks in bone marrow and
      embryonic cells. However, the embryos sired by the tamoxifen treated males had no
      effect on developmental milestones achieved and on their reproductive
      performance. The present study suggests that chromosomal aberrations observed in
      the embryos did not the affect their development until adulthood but could make
      the progeny of the tamoxifen treated males vulnerable to the development of adult
      onset diseases later in life.

PMID- 20801231
TI  - Assessment of the cytotoxicity and genotoxicity of haloacetic acids using
      microplate-based cytotoxicity test and CHO/HGPRT gene mutation assay.
AB  - Haloacetic acids (HAAs) are the second most prevalent class of disinfection
      byproducts found in drinking water. The implications of HAAs presence in drinking
      water are a public health concern due to their potential mutagenic and
      carcinogenic effects. In the present study, we examined the cytotoxic and
      genotoxic effects of six common HAAs using a microplate-based cytotoxicity test
      and a hypoxanthine-guanine phosphoribosyltransferase (HGPRT) gene mutation assay
      in Chinese hamster ovary K1 (CHO-K1) cells. We found that their chronic
      cytotoxicities (72h exposure) to CHO-K1 cells varied, and we ranked their levels
      of toxicity in the following descending order: iodoacetic acid (IA)>bromoacetic
      acid (BA)>dibromoacetic acid (DBA)>chloroacetic acid (CA)>dichloroacetic acid
      (DCA)>trichloroacetic acid (TCA). The toxicity of IA is 1040-fold of that of TCA.
      All HAAs except TCA were shown to be mutagenic to CHO-K1 cells in the HGPRT gene
      mutation assay. The mutagenic potency was compared and ranked as follows:
      IA>DBA>BA>CA>DCA>TCA. There was a statistically significant correlation between
      cytotoxicity and mutagenicity of the HAAs in CHO-K1 cells. The microplate-based
      cytotoxicity assay and HGPRT gene mutation assay were suitable methods to monitor
      the cytotoxicity and genotoxicity of HAAs, particularly for comparing the toxic
      intensities quantitatively.

PMID- 20801232
TI  - Antimutagenic; differentiation-inducing; and antioxidative effects of fragrant
      ingredients in Katsura-uri (Japanese pickling melon; Cucumis melo var. conomon).
AB  - Six fragrant ingredients were identified in fully-ripened Katsura-uri (Japanese
      pickling melon; Cucumis melo var. conomon). Four of them were sulfur-containing
      compounds [methylthioacetic acid ethyl ester (MTAE), acetic acid 2-methylthio
      ethyl ester (AMTE), 3-methylthiopropionic acid ethyl ester (MTPE), and acetic
      acid 3-methylthio propyl ester (AMTP)]; and the others were benzyl acetate and
      eugenol. The newly identified MTAE and AMTP possessed antimutagenic activity as
      determined by their ability to inhibit the UV-induced mutation in repair
      proficient E. coli B/r WP2. MTAE and MTPE (esters with thiocarbonic acid and
      alkyl alcohol) induced the differentiation of human colon cancer cells (RCM-1
      cells), but AMTE and AMTP (esters with carbonic acid and thioalkyl alcohol) did
      not. A specific thioester motif containing a thiocarbonic acid and alkyl alcohol
      correlated with these compounds ability to induce differentiation. AMTE, MTPE,
      AMTP, and eugenol had higher oxygen radical absorbing capacity than the
      antioxidative vitamin, ascorbic acid. The quantity of MTPE, AMTP and eugenol
      increased 49-fold, >1175-fold and 11-fold, respectively, in the fully-ripened
      fruit as compared to the mid-ripened fruit.

PMID- 20801233
TI  - An overview of the "Positive Action for Today's Health" (PATH) trial for
      increasing walking in low income, ethnic minority communities.
AB  - BACKGROUND: Ethnic minorities and lower-income adults have among the highest
      rates of obesity and lowest levels of regular physical activity (PA). The
      Positive Action for Today's Health (PATH) trial compares three communities that
      are randomly assigned to different levels of an environmental intervention to
      improve safety and access for walking in low income communities. DESIGN AND
      SETTING: Three communities matched on census tract information (crime, PA, ethnic
      minorities, and income) were randomized to receive either: an intervention that
      combines a police-patrolled-walking program with social marketing strategies to
      promote PA, a police-patrolled-walking only intervention, or no-walking
      intervention (general health education only). Measures include PA (7-day
      accelerometer estimates), body composition, blood pressure, psychosocial
      measures, and perceptions of safety and access for PA at baseline, 6, 12, 18, and
      24 months. INTERVENTION: The police-patrolled walking plus social marketing
      intervention targets increasing safety (training community leaders as walking
      captains, hiring off-duty police officers to patrol the walking trail, and
      containing stray dogs), increasing access for PA (marking a walking route), and
      utilizes a social marketing campaign that targets psychosocial and environmental
      mediators for increasing PA. MAIN HYPOTHESES/OUTCOMES: It is hypothesized that
      the police-patrolled walking plus social marketing intervention will result in
      greater increases in moderate-to-vigorous PA as compared to the police-patrolled
      walking only or the general health intervention after 12 months and that this
      effect will be maintained at 18 and 24 months. CONCLUSIONS: Implications of this
      community-based trial are discussed.

PMID- 20801234
TI  - PorA VR3 Typing Database: a web-based resource for the determination of PorA VR3
      alleles of Neisseria meningitidis.
AB  - The variable regions (VR) of the surface-exposed PorA protein of Meningococci are
      used for subtyping and are considered the most abundant epitopes of outer
      membrane vesicle-based vaccine preparations. We have developed both a database
      that maintains all the known VR3 alleles and a web-based application for the
      rapid identification and submission of new VR3 variants based on sequence
      comparison.

PMID- 20801235
TI  - Redox signaling and reactive oxygen species in hypoxic pulmonary
      vasoconstriction.
AB  - Hypoxic pulmonary vasoconstriction (HPV) is an essential physiological mechanism
      of the lung that matches blood perfusion with alveolar ventilation to optimize
      gas exchange. Perturbations of HPV, as may occur in pneumonia or adult
      respiratory distress syndrome, can cause life-threatening hypoxemia. Despite
      intensive research for decades, the molecular mechanisms of HPV have not been
      fully elucidated. Reactive oxygen species (ROS) and changes in the cellular redox
      state are proposed to link O2 sensing and pulmonary arterial smooth muscle cell
      contraction underlying HPV. In this regard, mitochondria and NAD(P)H oxidases are
      discussed as sources of ROS. However, there is controversy whether ROS levels
      decrease or increase during hypoxia. With this background we summarize the
      current knowledge on the role of ROS and redox state in HPV.

PMID- 20801237
TI  - The role of redox changes in oxygen sensing.
AB  - The specialized oxygen-sensing tissues include the carotid body and arterial
      smooth muscle cells in the pulmonary artery (PA) and ductus arteriosus (DA). We
      discuss the evidence that changes in oxygen tension are sensed through changes in
      redox status. "Redox" changes imply the giving or accepting of electrons. This
      might occur through the direct tunneling of electrons from mitochondria or redox
      couples to an effector protein (e.g. ion channel). Alternatively, the electron
      might be transferred through reactive oxygen species from mitochondria or an
      NADPH oxidase isoform. The PA's response to hypoxia and DA's response to normoxia
      result from reduction or oxidation, respectively. These opposing redox stimuli
      lead to K+ channel inhibition, membrane depolarization and an increase in
      cytosolic calcium and/or calcium sensitization that causes contraction. In the
      neuroendocrine cells (the type 1 cell of the carotid body, neuroepithelial body
      and adrenomedullary cells), the response is secretion. We examine the roles
      played by superoxide anion, hydrogen peroxide and the anti-oxidant enzymes in the
      signaling of oxygen tensions.

PMID- 20801239
TI  - Cell redox state and hypoxic pulmonary vasoconstriction: recent evidence and
      possible mechanisms.
AB  - During alveolar hypoxia, hypoxic pulmonary vasoconstriction (HPV) maintains blood
      oxygenation near optimum via incompletely defined mechanisms. It is proposed that
      a hypoxia-induced rise in the intracellular concentration of reactive oxygen
      species (ROS) or an oxidising shift in the cytoplasmic redox state provides the
      signal which initiates the constriction of pulmonary arteries (PA), although this
      is controversial. Here, we review recent investigations demonstrating that
      hypoxia causes a rise in [ROS] in PA smooth muscle, and that ROS and antioxidants
      have effects on PA which would be predicted if cell oxidation causes contraction.
      We argue that intracellular Ca2+ release and Ca2+-sensitisation are the key
      effector mechanisms causing HPV, and discuss evidence that both processes are
      promoted by ROS or oxidative protein modifications. We conclude that while it is
      plausible that an increase in cytoplasmic [ROS] activates HPV effector
      mechanisms, proving this link will require the determination of whether hypoxia
      causes oxidative modifications of proteins involved in Ca2+ homeostasis and
      sensitisation.

PMID- 20801236
TI  - The role of serotonin in respiratory function and dysfunction.
AB  - Serotonin (5-HT) is a neuromodulator-transmitter influencing global brain
      function. Past and present findings illustrate a prominent role for 5-HT in the
      modulation of ponto-medullary autonomic circuits. 5-HT is also involved in the
      control of neurotrophic processes during pre- and postnatal development of neural
      circuits. The functional implications of 5-HT are particularly illustrated in the
      alterations to the serotonergic system, as seen in a wide range of neurological
      disorders. This article reviews the role of 5-HT in the development and control
      of respiratory networks in the ponto-medullary brainstem. The review further
      examines the role of 5-HT in breathing disorders occurring at different stages of
      life, in particular, the neonatal neurodevelopmental diseases such as Rett,
      sudden infant death and Prader-Willi syndromes, adult diseases such as sleep
      apnoea and mental illness linked to neurodegeneration.

PMID- 20801240
TI  - Enhanced regeneration of the ligament-bone interface using a poly(L-lactide-co
      epsilon-caprolactone) scaffold with local delivery of cells/BMP-2 using a heparin
      based hydrogel.
AB  - Recently, the ligament-bone (LTB) junction has been emphasized for the effective
      transmission of mechanical force and the reduction in stress concentration
      between the soft ligament and hard bone tissue. The aim of this study was to
      regenerate an integrated LTB interface by inoculating LTB-relevant cells,
      isolated from fibrocartilage (FC) or ligament (LIG), separately into each
      designated region in a single porous cylindrical PLCL scaffold. An injectable,
      heparin-based hydrogel that has proved to be effective in the culture of
      chondrocytes as well as the sustained release of growth factor was employed to
      locally deliver fibrochondrocytes and osteoinductive bone morphogenetic protein-2
      (BMP-2) into the FC region, to promote FC regeneration. In in vitro experiments
      the hydrogel-combined FC systems produced significantly larger amounts of calcium
      and glycosaminoglycans (GAGs), but less collagen and DNA than FC samples without
      the hydrogel and all LIG samples. After in vivo subcutaneous implantation in mice
      for 8 weeks the secreted calcium and GAG contents of the hydrogel-containing FC
      samples were superior or similar to those of the in vitro hydrogel-containing FC
      samples at 6 weeks. As a result of the enhanced production of calcium and GAG,
      the in vivo hydrogel-containing FC samples produced the highest compressive
      modulus among all samples. Histological and immunofluorescence analysis as well
      as elemental analysis also confirmed a denser and more homogeneous distribution
      of calcium, GAG, osteocalcin and neovascularization marker in the in vitro/in
      vivo hydrogel-containing FC systems than those without hydrogel. These results
      also show the beneficial effects of BMP-2 added using the hydrogel. In summary,
      the use of a heparin-based hydrogel for the local delivery of fibrochondrocytes
      and BMP-2 could accelerate the maturation and differentiation of LTB-specific FC
      tissues, and it was also possible to recreate the unique stratification of
      calcified FC and LIG tissues in a single porous PLCL scaffold in terms of both
      biochemical and biomechanical properties.

PMID- 20801238
TI  - Interactions between calcium and reactive oxygen species in pulmonary arterial
      smooth muscle responses to hypoxia.
AB  - In contrast to the systemic vasculature, where hypoxia causes vasodilation,
      pulmonary arteries constrict in response to hypoxia. The mechanisms underlying
      this unique response have been the subject of investigation for over 50 years,
      and still remain a topic of great debate. Over the last 20 years, there has
      emerged a general consensus that both increases in intracellular calcium
      concentration and changes in reactive oxygen species (ROS) generation play key
      roles in the pulmonary vascular response to hypoxia. Controversy exists, however,
      regarding whether ROS increase or decrease during hypoxia, the source of ROS, and
      the mechanisms by which changes in ROS might impact intracellular calcium, and
      vice versa. This review will discuss the mechanisms regulating [Ca2+]i and ROS in
      PASMCs, and the interaction between ROS and Ca2+ signaling during exposure to
      acute hypoxia.

PMID- 20801241
TI  - A novel spatially designed and functionally graded electrospun membrane for
      periodontal regeneration.
AB  - A periodontal membrane with a graded structure allows tailoring of the layer
      properties to design a material system that will retain its physical, chemical
      and mechanical characteristics for a period long enough to optimize periodontal
      regeneration. In this work a novel functionally graded membrane (FGM) was
      designed and fabricated via sequential multilayer electrospinning. The FGM
      consists of a core layer (CL) and two functional surface layers (SLs) interfacing
      with bone (nano-hydroxyapatite, n-HAp) and epithelial (metronidazole, MET)
      tissues. The CL comprises a neat poly(DL-lactide-co-epsilon-caprolactone) (PLCL)
      layer surrounded by two composite layers composed of a protein/polymer ternary
      blend (PLCL:PLA:GEL). Electrospinning parameters involved in fabrication of the
      individual layers (i.e. neat PLCL, ternary blend, PLA:GEL+10%n-HAp and
      PLA:GEL+25%MET) were optimized to obtain fibrous layers free of beads.
      Morphology, structure and mechanical property studies were carried out on each
      electrospun layer. The individual fiber morphology and roughness of the
      functional SLs, which are the n-HAp containing and drug-incorporating layers were
      evaluated by atomic force microscopy. The CL structure demonstrated higher
      strength (8.7 MPa) and a more elastic behavior (strain at break 357%) compared
      with the FGM (3.5 MPa, 297%). Incorporation of n-HAp to enhance osteoconductive
      behavior and MET to combat periodontal pathogens led to a novel FGM that holds
      promise at solving the drawbacks of currently available membranes.

PMID- 20801243
TI  - A rare complication of chemotherapy in a 56-year-old patient. Gastric emphysema.

PMID- 20801242
TI  - Covalently immobilized platelet-derived growth factor-BB promotes angiogenesis in
      biomimetic poly(ethylene glycol) hydrogels.
AB  - The field of tissue engineering is severely limited by a lack of
      microvascularization in tissue engineered constructs. Biomimetic poly(ethylene
      glycol) hydrogels containing covalently immobilized platelet-derived growth
      factor BB (PDGF-BB) were developed to promote angiogenesis. Poly(ethylene glycol)
      hydrogels resist protein absorption and subsequent non-specific cell adhesion,
      thus providing a "blank slate", which can be modified through the incorporation
      of cell adhesive ligands and growth factors. PDGF-BB is a key angiogenic protein
      able to support neovessel stabilization by inducing functional anastomoses and
      recruiting pericytes. Due to the widespread effects of PDGF in the body and a
      half-life of only 30 min in circulating blood, immobilization of PDGF-BB may be
      necessary. In this work bioactive, covalently immobilized PDGF-BB was shown to
      induce tubulogenesis on two-dimensional modified surfaces, migration in three
      dimensional (3D) degradable hydrogels and angiogenesis in a mouse cornea
      micropocket angiogenesis assay. Covalently immobilized PDGF-BB was also used in
      combination with covalently immobilized fibroblast growth factor-2, which led to
      significantly increased endothelial cell migration in 3D degradable hydrogels
      compared with the presentation of each factor alone. When a co-culture of
      endothelial cells and mouse pericyte precursor 10T1/2 cells was seeded onto
      modified surfaces tubule formation was independent of surface modifications with
      covalently immobilized growth factors. Furthermore, the combination of soluble
      PDGF-BB and immobilized PDGF-BB induced a more robust vascular response compared
      with soluble PDGF-BB alone when implanted into an in vivo mouse cornea
      micropocket angiogenesis assay. Based on these results, we believe bioactive
      hydrogels can be tailored to improve the formation of functional microvasculature
      for tissue engineering.

PMID- 20801244
TI  - Middle- and high-school health education regarding adolescent vaccines and human
      papillomavirus.
AB  - We performed a mail-based survey of health education teachers in 6 states with
      diverse health education environments to better understand health education
      curricula in secondary schools related to adolescent vaccination and human
      papillomavirus (HPV) infection. Of the 198 respondents (response rate 68%), 66%
      and 71% reported teaching adolescents about recommended vaccines and HPV,
      respectively. Middle schools were significantly less likely to include these
      topics in their health curriculum than high schools even though middle schools
      are generally the school type attended by 11-12 year olds, the preferred target
      age for adolescent vaccination and HPV prevention activities.

PMID- 20801245
TI  - The 4th International Conference on Polyphenols and Health (ICPH2009).

PMID- 20801246
TI  - A randomized controlled trial comparing manipulation with mobilization for recent
      onset neck pain.
AB  - A randomized controlled trial comparing manipulation with mobilization for recent
      onset neck pain. OBJECTIVE: To determine whether neck manipulation is more
      effective for neck pain than mobilization. DESIGN: Randomized controlled trial
      with blind assessment of outcome. SETTING: Primary care physiotherapy,
      chiropractic, and osteopathy clinics in Sydney, Australia. PARTICIPANTS: Patients
      (N=182) with nonspecific neck pain less than 3 months in duration and deemed
      suitable for treatment with manipulation by the treating practitioner.
      INTERVENTIONS: Participants were randomly assigned to receive treatment with neck
      manipulation (n=91) or mobilization (n=91). Patients in both groups received 4
      treatments over 2 weeks. MAIN OUTCOME MEASURE: The number of days taken to
      recover from the episode of neck pain. RESULTS: The median number of days to
      recovery of pain was 47 in the manipulation group and 43 in the mobilization
      group. Participants treated with neck manipulation did not experience more rapid
      recovery than those treated with neck mobilization (hazard ratio=.98; 95%
      confidence interval, .66-1.46). CONCLUSIONS: Neck manipulation is not appreciably
      more effective than mobilization. The use of neck manipulation therefore cannot
      be justified on the basis of superior effectiveness.

PMID- 20801247
TI  - Forgoing physician visits because of cost: a source of health disparities for
      elderly people with disabilities?
AB  - OBJECTIVE: To examine disparities in having a usual source of care and forgoing
      physician visits because of cost between elderly people (age > or =65y) with and
      without disabilities after consecutively controlling for predisposing, enabling,
      and perceived and evaluated health need factors using the Andersen behavioral
      model, and to identify the determinants of such disparities. DESIGN: Cross
      sectional analysis. SETTING: Community. PARTICIPANTS: Nationally representative
      sample of community-dwelling adults age 65 years or greater in the United States
      from the 2006 Behavioral Risk Factor Surveillance System (BRFSS) (N=93,933).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Responses to 2 BRFSS
      questions: (1) whether the respondent had a health care provider, and (2) whether
      the respondent had forgone seeing a physician because of cost in the past 12
      months. RESULTS: After controlling for the aforementioned factors, elderly
      persons with disabilities were more likely than their counterparts without
      disabilities to have a usual source of care (adjusted odds ratio [AOR]=1.33; 95%
      confidence interval [CI], 1.08-1.64), and those with disabilities were more
      likely to forgo physician visits because of cost (AOR=1.64; 95% CI, 1.31-2.04).
      The unadjusted odds of forgoing physician visits (odds ratio [OR]=2.13; 95% CI,
      1.87-2.43) did not decrease after controlling for predisposing factors (AOR=2.32;
      95% CI, 1.96-2.75), whereas the odds were attenuated after controlling for
      enabling factors (AOR=2.18; 95% CI, 1.84-2.59), perceived health need (AOR=1.70;
      95% CI, 1.37-2.12), and evaluated health need (AOR=1.64; 95% CI, 1.31-2.04).
      CONCLUSIONS: Although elderly people with disabilities were more likely than
      their counterparts without disabilities to have a usual source of care, those
      with disabilities were more likely to forgo physician visits because of cost.
      Elderly persons with greater perceived health needs were most likely to
      experience the disparity.

PMID- 20801248
TI  - Comparison of trunk proprioception between patients with low back pain and
      healthy controls.
AB  - OBJECTIVE: To determine whether proprioceptive impairments exist in patients with
      low back pain (LBP). We hypothesized that patients with LBP would exhibit larger
      trunk proprioception errors than healthy controls. DESIGN: Case-control study.
      SETTING: University laboratory. PARTICIPANTS: 24 patients with nonspecific LBP
      and 24 age-matched healthy controls. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: We measured trunk proprioception in all 3 anatomical planes using
      motion perception threshold, active repositioning, and passive repositioning
      tests. RESULTS: LBP patients had significantly greater motion perception
      threshold than controls (P<.001) (1.3+/-0.9 degrees vs 0.8+/-0.6 degrees ).
      Furthermore, all subjects had the largest motion perception threshold in the
      transverse plane (P<.001) (1.2+/-0.7 degrees vs 1.0+/-0.8 degrees for all other
      planes averaged). There was no significant difference between LBP and healthy
      control groups in the repositioning tasks. Errors in the active repositioning
      test were significantly smaller than in the passive repositioning test (P=.032)
      (1.9+/-1.2 degrees vs 2.3+/-1.4 degrees ). CONCLUSIONS: These findings suggest
      that impairments in proprioception may be detected in patients with LBP when
      assessed with a motion perception threshold measure.

PMID- 20801249
TI  - Preparation for compensatory forward stepping in Parkinson's disease.
AB  - OBJECTIVE: To characterize preparation for compensatory stepping in people with
      Parkinson's disease (PD) compared with healthy control subjects, and to determine
      whether levodopa medication improves preparation or the execution phases of the
      step. DESIGN: Observational study. SETTING: Outpatient neuroscience laboratory.
      PARTICIPANTS: Nineteen participants with idiopathic PD tested both in the on and
      off levodopa states and 17 healthy subjects. INTERVENTION: Moveable platform with
      posterior translations of 24cm at 56cm/s. MAIN OUTCOME MEASURES: Compensatory
      steps forward, in response to a backward surface translation (24cm amplitude at
      56cm/s), were categorized according to the presence of an anticipatory postural
      adjustment (APA) before stepping: no APA, single APA, or multiple APAs. The
      following step parameters were calculated: step latency, step length, center of
      mass (CoM) average velocity, and CoM displacement at the step initiation.
      RESULTS: Lateral APAs were evident in 57% and 42% of trials for people with PD in
      the off and on medication states, respectively, compared with only 10% of trials
      for control subjects. Compared with subjects with PD who did not have APAs, those
      subjects with PD who did make an APA prior to stepping had significantly later
      (mean +/- SEM, 356+/-16ms vs 305+/-8ms) and shorter (mean +/- SEM, 251+/-27mm vs
      300+/-16mm) steps, their CoM was significantly farther forward (185+/-7mm vs
      171+/-5mm) at foot-off, and they took significantly more steps to regain
      equilibrium. Levodopa did not affect the preparation or execution phase of
      compensatory stepping. Poor axial scores and reports of freezing in the United
      Parkinson's Disease Rating Scale were associated with use of 1 or more APAs
      before compensatory stepping. CONCLUSIONS: Lateral postural preparation prior to
      compensatory stepping in subjects with PD was associated with inefficient balance
      recovery from external perturbations.

PMID- 20801250
TI  - Case-mix adjustment and enabled reporting of the health care experiences of
      adults with disabilities.
AB  - OBJECTIVES: To develop activity limitation clusters for case-mix adjustment of
      health care ratings and as a population profiler, and to develop a cognitively
      accessible report of statistically reliable quality and access measures comparing
      the health care experiences of adults with and without disabilities, within and
      across health delivery organizations. DESIGN: Observational study. SETTING: Three
      California Medicaid health care organizations. PARTICIPANTS: Adults (N = 1086) of
      working age enrolled for at least 1 year in Medicaid because of disability.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Principal components
      analysis created 4 clusters of activity limitations that we used to characterize
      case mix. We identified and calculated 28 quality measures using responses from a
      proposed enabled version of the Consumer Assessment of Healthcare Providers and
      Systems (CAHPS) survey. We calculated scores for overall care as the weighted
      mean of the case-mix adjusted ratings. RESULTS: Disability caused a greater bias
      on health plan ratings and specialist ratings than did demographic factors. Proxy
      respondents rated care the same as self-respondents. Telephone and mail
      administration were equivalent for service reports, but telephone respondents
      tended to offer more positive global ratings. Plan-level reliability estimates
      for new composites on shared decision making and advice on healthy living are .79
      and .87, respectively. Plan-level reliability estimates for a new composite
      measure on family planning did not discriminate between health plans because
      respondents rated all health plans poorly. Approximately 125 respondents per site
      are necessary to detect group differences. CONCLUSIONS: Self-reported activity
      limitations incorporating standard questions from the American Community Survey
      can be used to create a disability case-mix index and to construct profiles of a
      population's activity limitations. The enabled comparative report, which we call
      the Assessment of Health Plans and Providers by People with Activity Limitations,
      is more cognitively accessible than typical CAHPS report templates for state
      Medicaid plans. The CAHPS Medicaid reporting tools may provide misleading ratings
      of health plan and physician quality by people with disabilities because the mean
      ratings do not account for systematic biases associated with disability. More
      testing on larger populations would help to quantify the strength of various
      reporting biases.

PMID- 20801252
TI  - Impact of traumatic brain injury on participation in leisure activities.
AB  - OBJECTIVE: To determine how participation in leisure activities for people with
      traumatic brain injury (TBI) changes from before injury to 1 year after injury.
      DESIGN: Prospective evaluation of leisure participation at 1 year after TBI.
      SETTING: Level I trauma center. PARTICIPANTS: Rehabilitation inpatients (mean
      age, 35.3 years; 77% male; 77% white) with moderate to severe TBI (N=160).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Functional Status
      Examination. RESULTS: At 1 year after injury, 81% had not returned to preinjury
      levels of leisure participation. Activities most frequently discontinued included
      partying, drug and alcohol use, and various sports. The activity most often
      reported as new after injury was watching television. Of the small fraction who
      returned to preinjury levels, 70% did so within 4 months of injury. Sixty percent
      of those who did not return to preinjury levels were moderately to severely
      bothered by the changes. CONCLUSIONS: At 1 year after injury, many TBI survivors
      engage in a reduced number of leisure activities, which are more sedentary and
      less social, with a substantial fraction dissatisfied with these changes. While
      discontinuing some activities may be viewed as a positive change, there are few
      new ones to replace them.

PMID- 20801251
TI  - Development and validation of participation and positive psychologic function
      measures for stroke survivors.
AB  - OBJECTIVE: To evaluate the reliability and validity of Neurologic Quality of Life
      (NeuroQOL) item banks that assess quality-of-life (QOL) domains not typically
      included in poststroke measures. DESIGN: Secondary analysis of item responses to
      selected NeuroQOL domains. SETTING: Community. PARTICIPANTS: Community-dwelling
      stroke survivors (n=111) who were at least 12 months poststroke. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Five measures developed for 3 NeuroQoL
      domains: ability to participate in social activities, satisfaction with
      participation in social activities, and positive psychologic function. RESULTS: A
      single bank was developed for the positive psychologic function domain, but 2
      banks each were developed for the ability-to-participate and satisfaction-with
      participation domains. The resulting item banks showed good psychometric
      properties and external construct validity with correlations with the legacy
      instruments, ranging from .53 to .71. Using these measures, stroke survivors in
      this sample reported an overall high level of QOL. CONCLUSIONS: The NeuroQoL
      derived measures are promising and valid methods for assessing aspects of QOL not
      typically measured in this population.

PMID- 20801253
TI  - Baseline comorbidity associated with the short-term effects of exercise
      intervention on quality of life in the Japanese older population: an
      observational study.
AB  - Tamari K. Baseline comorbidity associated with the short-term effects of exercise
      intervention on quality of life in the Japanese older population: an
      observational study. OBJECTIVE: To investigate predictors of responses to a class
      based exercise program in terms of health-related quality of life (HRQOL).
      DESIGN: A 3-month prospective cohort study. SETTING: General community.
      PARTICIPANTS: A sample of community-dwelling Japanese volunteers (N=137; aged >
      or =65y) initially was included in the study. More than three fourths (76.6%)
      completed the follow-up examination. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Eight domains of the Medical Outcomes Study 36-Item Short-Form Health
      Survey, version 2, were used as main outcome measures. Candidate predictors
      included demographic variables, medical history of chronic diseases, and results
      of a set of physical performance tests at the baseline examination. Logistic
      regression models were used to detect predictors. RESULTS: Bodily pain, vitality,
      social functioning, and mental health domains improved after the intervention
      (P<.01 vs baseline). The absence of diabetes mellitus showed an association with
      a good response in the identified domains, with an adjusted odds ratio (OR) of
      2.88 (confidence interval [CI], .90-9.25). More than 20% of participants had
      negative changes in the physical functioning, physical role, general health, and
      emotional role domains at follow-up. The presence of osteoarthritis significantly
      predicted a poor response in these domains, with an adjusted OR of 6.75 (CI, 1.58
      28.83). CONCLUSIONS: Three months of class-based exercise is effective in
      alleviating bodily pain and the mental components of HRQOL; however, the effect
      of exercise on the physical domains of HRQOL may be limited. The presence of
      osteoarthritis may moderate the effects of exercise on HRQOL physical components.

PMID- 20801254
TI  - Suggestions for refinement of the Disabilities of the Arm, Shoulder and Hand
      Outcome Measure (DASH): a factor analysis and Rasch validation study.
AB  - OBJECTIVE: To perform a comprehensive psychometric analysis of Disabilities of
      the Arm, Shoulder and Hand (DASH) to examine its properties and provide insights
      for an improved version. DESIGN: Methodologic research on cross-sectional data
      from a convenience sample. SETTING: A free-standing rehabilitation center.
      PARTICIPANTS: Outpatients and inpatients (N=238; 56% men; mean age, 52.2y) with
      upper-extremity musculoskeletal disorders. MAIN OUTCOME MEASURE: The official
      Italian version of DASH was analyzed by factor (both explorative and
      confirmatory) and Rasch analysis for evaluating dimensionality, functioning of
      rating scale categories, item fit, hierarchy of item difficulties, and
      reliability indices. INTERVENTIONS: Not applicable. RESULTS: Factor analysis
      established the presence of 3 underlying constructs related to manual functioning
      (items 1-5, 7-11, 16-18, 20, 21), shoulder range of motion (items 6, 12-15, 19),
      and symptoms and consequences (items 22-30). Rating scale diagnostics showed
      category malfunctioning. The fit to the Rasch model was good for all items except
      4 (items 20, 21, 25, 26). Ten item pairs had high residual correlations after
      subtraction of the Rasch dimension (local dependency). A test model based on the
      3 subscales suggested by factor analysis and corrected categories still showed
      misfitting in items 21 ("Sexual Activities") and 26 ("Tingling") and the presence
      of some dependent items. CONCLUSIONS: Unidimensionality and the key domains
      identified by the original developers as the theoretic framework of DASH were not
      confirmed by our analyses. The response categories showed misfunctioning. "Sexual
      Activities" and "Tingling" misfit the Rasch model. Further detailed
      investigations of DASH are warranted, both to confirm these results in different
      health conditions and cultures, and to reanalyze in-depth content validity issues
      regarding the questionnaire.

PMID- 20801255
TI  - Electric pulse frequency and magnitude of perceived sensation during
      electrocutaneous forearm stimulation.
AB  - OBJECTIVES: To investigate the effect that electric pulse frequency has on the
      perceived magnitude of sensation and to quantify the relationship between
      electric pulse frequency and perceived magnitude of sensation during low
      intensity electrocutaneous stimulation. DESIGN: A repeated-measures research
      design was applied to evaluate the effect of electric pulse frequency on the
      perceived magnitude of electrocutaneous stimulation. SETTING: Electrocutaneous
      agents laboratory. PARTICIPANTS: University students (N=26) with normal hearing
      and normal sensation were recruited for the study. INTERVENTIONS:
      Electrocutaneous stimulation was applied to the forearm at 10 electric pulse
      frequencies. MAIN OUTCOME MEASURES: A cross-modality matching procedure was used
      in which stimulation intensity was matched with the level of loudness. Pairwise
      comparisons with 2 degrees of freedom at a power of 80% was performed.
      Statistical significance was set at P equal to .05. RESULTS: Electric pulse
      frequency had a significant effect on the perceived magnitude of sensation, with
      the perceived sensation growing between 0 and 120Hz (F=36.02; P<.001). The
      relationship between the 2 variables was strong (r(2)=.99; P<.01). CONCLUSIONS:
      Increasing the electric pulse frequency of electrocutaneous stimulation increases
      the perceived magnitude of the resulting sensation. This has implications for the
      use of electrocutaneous stimulation for both analgesia and muscle stimulation.

PMID- 20801256
TI  - Effect of taping on actual and perceived dynamic postural stability in persons
      with chronic ankle instability.
AB  - OBJECTIVE: To investigate whether 2 different mechanisms of ankle joint taping
      ([1] lateral subtalar sling or [2] fibular repositioning) can enhance actual and
      perceived dynamic postural stability in participants with chronic ankle
      instability (CAI). DESIGN: Laboratory-based repeated-measures study. SETTING:
      University biomechanics laboratory. PARTICIPANTS: Participants (n=16) with CAI.
      INTERVENTIONS: Participants performed the Star Excursion Balance Test (SEBT)
      under 3 different conditions: (1) no tape, (2) lateral subtalar sling taping and
      (3) fibular repositioning taping. MAIN OUTCOME MEASURES: Reach distances in the
      anterior, posteromedial, and posterolateral directions on the SEBT. Participants'
      perceptions of stability, confidence, and reassurance when performing the SEBT
      under 2 different taping conditions. RESULTS: Taping did not improve reach
      distance on the SEBT (P>.05). Feelings of confidence increased for 56% of
      participants (P=.002) under both tape conditions. Feelings of stability increased
      for 87.5% of participants (P<.001) using condition 2 (lateral subtalar sling
      taping) and 75% of participants (P=.001) using condition 3 (fibular repositioning
      taping). Feelings of reassurance increased for 68.75% of participants (P=.001)
      using condition 2 (lateral subtalar sling taping) and 50% of participants
      (P=.005) using condition 3 (fibular repositioning taping). CONCLUSIONS: No
      significant change in dynamic postural stability was observed after application
      of either taping mechanism; however, participants' perceptions of confidence,
      stability, and reassurance were significantly improved. Further research is
      necessary to fully elucidate the exact mechanisms by which taping may help reduce
      the incidence of repeated injury in subjects with CAI.

PMID- 20801257
TI  - Differences in preferred walking speeds in a gait laboratory compared with the
      real world after total hip replacement.
AB  - OBJECTIVE: To evaluate the relation between walking speeds measured in a gait
      laboratory and those measured in real-world settings (habitual speed) in subjects
      with total hip replacements (THRs) and control subjects. The secondary objective
      is to determine whether the relationship between gait laboratory and habitual
      speeds was affected by recovery time or related to clinical indices. DESIGN:
      Cohort study. SETTING: Academic medical center. PARTICIPANTS: Experimental
      subjects (n=26) evaluated 3 weeks and 12 months after THR and control subjects
      (n=24). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Walking speed measured in the
      gait laboratory, walking speed measured in the field by using activity monitors,
      Harris Hip Score (HHS), and the Western Ontario and McMaster Osteoarthritis Index
      (WOMAC). RESULTS: Laboratory speeds were significantly faster than habitual
      speeds in all groups (P<.001), but the 2 correlated significantly. The laboratory
      versus habitual-speed difference was unaffected by recovery time within the THR
      group (P=.180) but was larger for control subjects (.32+/-.21m/s) than for THR
      subjects (.19+/-.15m/s 1 year after surgery). Habitual speed significantly
      correlated with total WOMAC scores and with WOMAC stiffness and function
      subscores 3 weeks after THR. The HHS weakly correlated with 3-week laboratory
      speed. No speed and clinical correlations were seen 1 year after THR.
      CONCLUSIONS: Although subjects may exaggerate walking speeds in laboratory
      settings, laboratory-based data accurately reflect real-world activity. Setting
      affected speeds most in the control group. It is important to consider potential
      discrepancies between speeds walked in a laboratory versus in the real world when
      interpreting gait studies comparing 2 or more populations. Finally, analysis of
      these data suggests that clinical indices may more accurately reflect
      biomechanical function during early recovery after THR than after full recovery.

PMID- 20801258
TI  - Construct validity and test-retest reliability of the climbing stairs
      questionnaire in lower-limb amputees.
AB  - OBJECTIVE: To investigate the construct validity and test-retest reliability of
      the Climbing Stairs Questionnaire, a patient-reported measure of activity
      limitations in climbing stairs, in lower-limb amputees. DESIGN: A cross-sectional
      study. SETTING: Outpatient department of a rehabilitation center. PARTICIPANTS:
      Lower-limb amputees (N=172; mean +/- SD age, 65+/-12y; 71% men; 82% vascular
      cause) participated in the study; 33 participated in the reliability study.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Construct validity was
      investigated by testing 10 hypotheses: limitations in climbing stairs according
      to the Climbing Stairs Questionnaire will be greater in lower-limb amputees who:
      (1) are older, (2) have a vascular cause of amputation, (3) have a bilateral
      amputation, (4) have a higher level of amputation, (5) have more comorbid
      conditions, (6) had their rehabilitation treatment in a nursing home, and (7)
      climb fewer flights of stairs. Furthermore, limitations in climbing stairs will
      be related positively to activity limitations according to: (8) the Locomotor
      Capabilities Index, (9) the Questionnaire Rising and Sitting down, and (10) the
      Walking Questionnaire. Construct validity was quantified by using the Mann
      Whitney U test, Kruskal-Wallis test, and Spearman correlation coefficient. Test
      retest reliability was assessed with a 3-week interval and quantified using the
      intraclass correlation coefficient (ICC). RESULTS: Construct validity (8 of 10
      null hypotheses not rejected) and test-retest reliability were good (ICC=.79; 95%
      confidence interval, .57-.90). CONCLUSION: The Climbing Stairs Questionnaire has
      good construct validity and test-retest reliability in lower-limb amputees.

PMID- 20801260
TI  - Predicting exercise capacity through submaximal fitness tests in persons with
      multiple sclerosis.
AB  - OBJECTIVE: To estimate, for persons with multiple sclerosis (MS), the extent to
      which peak oxygen consumption (Vo(2)peak) can be predicted by the results on
      submaximal tests. DESIGN: Cross-sectional study. SETTING: Three MS clinics in the
      Greater Montreal region, Canada. PARTICIPANTS: A center-stratified random sample
      of 135 women and 48 men was drawn (N=183). A subgroup of 59 subjects with MS, who
      were able to perform the step test, was selected from this sample to complete the
      maximal exercise test. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE:
      Vo(2)peak. RESULTS: In this sample (mean age +/- SD, 39 +/- 9 y; median Expanded
      Disability Status Scale=1.5), the mean Vo(2)peak +/- SD was 27.6 +/- 7.3 mL.kg(
      1).min(-1). This value is considerably low when compared with healthy persons,
      ranking below the 25th percentile for both men and women. In a multivariate
      regression analysis, the step test and grip strength were identified as the only
      significant predictors of Vo(2)peak. When combined with body weight, grip
      strength and the step test explained 74% of the variance in Vo(2)peak.
      CONCLUSIONS: Patients with MS with a mild degree of disability exhibit marked
      reductions in exercise capacity. Also, in persons with MS, submaximal tests are
      good predictors of exercise capacity. These measures may be used in clinical
      settings to help assess and monitor maximum oxygen consumption and in research to
      evaluate the effect of exercise-related interventions. Furthermore, they will
      allow people with MS to self-monitor their exercise capacity and be more actively
      engaged in taking charge of their fitness level.

PMID- 20801261
TI  - Craniocervical orientation affects muscle activation when exercising the cervical
      extensors in healthy subjects.
AB  - OBJECTIVE: To evaluate the activity of neck extensor muscles during different
      extension exercises with muscle functional magnetic resonance imaging (mfMRI).
      DESIGN: Cross-sectional. SETTING: University laboratory. PARTICIPANTS: Healthy
      subjects (N=11; 7 men, mean age +/- SD, 34+/-5.6y; 4 women, mean age +/- SD,
      23.3+/-5.2y; group mean age +/- SD, 30.1+/-7.5y). INTERVENTION: Not applicable.
      MAIN OUTCOME MEASURES: mfMRI measures of T2 relaxation were made for the
      multifidus (Mul), the semispinalis cervicis (SCe), the semispinalis capitis
      (SCa), and the splenius capitis (SpC) at C2-3, C5-6, and C7-T1 in response to 2
      head/neck orientations: craniocervical neutral (CCN) and craniocervical extension
      (CCE). Subjects performed three 1-minute repetitions of each condition at 20%
      maximum voluntary contraction. RESULTS: Significant shifts were observed in all
      muscle groups at the C5-6 and C7-T1 levels after both conditions (P=.04) except
      the SpC muscle at C5-6 with CCN (P=.17). T2 shifts in the SCa were significantly
      greater in response to CCE than CCN at C2-3 (P=.03) and C5-6 (P=.02). Similarly,
      CCE resulted in larger shifts than CCN in the Mul/SCe at C7-T1 (P=.003). No
      segmental differences were observed between exercises for SpC (P=.25).
      CONCLUSIONS: The results of this study provide some preliminary insight into the
      impact of craniocervical orientation on the differential response of the deep and
      superficial cervical extensor muscles during the performance of cervical extensor
      exercises.

PMID- 20801259
TI  - Exploratory study on oxygen consumption on-kinetics during treadmill walking in
      women with systemic lupus erythematosus.
AB  - OBJECTIVE: To determine whether oxygen consumption (V o(2)) on-kinetics differed
      between groups of women with systemic lupus erythematosus (SLE) and sedentary but
      otherwise healthy controls. DESIGN: Exploratory case-control study. SETTING:
      Medical school exercise physiology laboratory. PARTICIPANTS: Convenience samples
      of women with SLE (n=12) and sedentary but otherwise healthy controls (n=10).
      INTERVENTION: None. MAIN OUTCOME MEASURES: V o(2) on-kinetics indices including
      time to steady state, rate constant, mean response time (MRT), transition
      constant, and oxygen deficit measured during bouts of treadmill walking at
      intensities of 3 and 5 metabolic equivalents (METs). RESULTS: Time to steady
      state and oxygen deficit were increased and rate constant was decreased in the
      women with SLE compared with controls. At the 5-MET energy demand, the transition
      constant was lower and MRT was longer in the women with SLE than in controls. For
      a similar relative energy expenditure that was slightly lower than the anaerobic
      threshold, the transition constant was higher in controls than in women with SLE.
      CONCLUSION: V o(2) on-kinetics was prolonged in women with SLE. The prolongation
      was concomitant with an increase in oxygen deficit and may underlie performance
      fatigability in women with SLE.

PMID- 20801262
TI  - Development of romantic relationships and sexual activity in young adults with
      cerebral palsy: a longitudinal study.
AB  - OBJECTIVES: To describe the development of romantic relationships and sexual
      activity of young adults with cerebral palsy (CP), to investigate whether this
      development is associated with demographic and physical characteristics, and to
      compare the sexual activity of this group with an age-appropriate Dutch reference
      population. DESIGN: Prospective longitudinal study with 3 biannual assessments.
      SETTING: Eight rehabilitation centers and departments in the southwestern regions
      of The Netherlands. PARTICIPANTS: Young adults (N=103; 61 men, 42 women) with CP
      without cognitive disabilities (age range at first assessment, 16-20 y; 82% Gross
      Motor Function Classification System level I or II). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Sexual interest, romantic relationships, and
      sexual activity. RESULTS: We observed a significant increase in dating in young
      adults with CP during the 4-year period; however, the experience in romantic
      relationships did not increase largely during this period. Young adults with a
      lower education level began dating later than those with higher levels.
      Significantly more women were in current romantic relationships than men. During
      the 4 years, participants' sexual experience increased significantly for all
      sexual milestones evaluated. Level of gross motor function was associated
      significantly with intercourse experience. Compared with an age-appropriate Dutch
      reference population, young adults with CP participated at a lower level in
      romantic relationships and sexual activities, but had equal sexual interest at
      the final assessment. CONCLUSIONS: Young ambulatory adults with CP had similar
      sexual interests and had increasing experiences with romantic relationships and
      sexual activities during the transition from late adolescence to young adulthood.
      However, the percentage of young adults with CP in current romantic relationships
      was low, especially for men.

PMID- 20801263
TI  - Effects of midodrine hydrochloride on blood pressure and cerebral blood flow
      during orthostasis in persons with chronic tetraplegia.
AB  - OBJECTIVE: To determine the mean arterial pressure (MAP) and middle cerebral
      artery mean blood flow velocity (MFV) responses to 5 and 10mg midodrine during
      head-up tilt (HUT) in persons with tetraplegia. DESIGN: Prospective dose-response
      trial. SETTING: James J. Peters Veterans Administration Medical Center.
      PARTICIPANTS: Persons (N=10) with chronic tetraplegia (duration of injury=23+/-11
      y). INTERVENTION: A dose titration study was performed over 3 testing days:
      control (no drug), 5mg midodrine (5mg), or 10mg midodrine (10mg) during 30
      minutes of baseline (predrug/no drug), 30 minutes of supine rest postdrug/no
      drug, 15 minutes of progressive HUT (5 minutes at 15 degrees , 25 degrees , 35
      degrees ), and 45 minutes of 45 degrees HUT. MAIN OUTCOME MEASURES: MAP and MFV
      response to midodrine supine and during HUT. RESULTS: Ten milligrams of midodrine
      significantly increased MAP while supine and during the HUT maneuver. Of note,
      the mean increase in MAP during HUT with 10mg was a result of a robust effect in
      2 persons, with minimal change in the remaining 8 study subjects. The reduction
      in cerebral MFV during HUT was attenuated with 10mg. CONCLUSIONS: These findings
      suggest that midodrine 10mg may be efficacious for treatment of hypotension and
      orthostatic hypotension in select persons with tetraplegia. Although midodrine is
      routinely prescribed to treat orthostatic hypotension, the results of our work
      suggests limited efficacy of this agent, but additional studies in a larger
      sample of subjects with spinal cord injury should be performed.

PMID- 20801264
TI  - Cognitive and behavioral impairment in traumatic brain injury related to outcome
      and return to work.
AB  - OBJECTIVE: To evaluate the cognitive and behavioral disturbances related to
      return to work (RTW) in patients with traumatic brain injury (TBI) with the
      application of a differentiated outcome scale. DESIGN: Longitudinal cohort study.
      SETTING: Level I trauma center. PARTICIPANTS: Adults (N=434) with TBI of various
      severity. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Extended Glasgow
      Outcome Scale (GOS-E), Differentiated Outcome Scale (DOS), and RTW. RESULTS:
      Patients encountered problems in the physical (40%), cognitive (62%), behavioral
      (55%), and social domains (49%) of the DOS, with higher frequency related to
      severity of injury. Even those with mild TBI experienced cognitive (43%) and
      behavioral problems (33%). Patients with good recovery (58%) according to the GOS
      E experienced problems in 1 or more domains of the DOS. Half the patients were
      able to resume previous vocational activities completely, although 1 in 3
      experienced cognitive or behavioral problems. Using multivariate logistic
      regression analysis, the cognitive (odds ratio [OR], 10.548; confidence interval
      [CI], 5.99-18.67), behavioral (OR, 2.648; CI, 1.63-4.29), and physical domains
      (OR, 2.763; CI, 1.60-4.78) were significant (P<.01) predictors of RTW. For
      subcategories of TBI, the cognitive domain was predictive for RTW in those with
      moderate and severe TBI, whereas both the cognitive and behavioral domains were
      predictive for RTW in those with mild TBI. CONCLUSIONS: With application of a
      more detailed outcome scale, cognitive and behavioral impairments interfering
      with RTW were present in a substantial part of patients with TBI in the chronic
      phase after injury. More research is needed exploring the cognitive and
      behavioral outcome in different categories of injury severity separately.

PMID- 20801265
TI  - Learning to control opening and closing a myoelectric hand.
AB  - OBJECTIVE: To compare 3 different types of myoelectric signal training. DESIGN: A
      cohort analytic study. SETTING: University laboratory. PARTICIPANTS: Able-bodied
      right-handed participants (N=34) randomly assigned to 1 of 3 groups.
      INTERVENTIONS: Participants trained hand opening and closing on 3 consecutive
      days. One group trained with a virtual myoelectric hand presented on a computer
      screen, 1 group trained with an isolated prosthetic hand, and 1 group trained
      with a prosthetic simulator. One half of the participants trained with their
      dominant side, and the other half trained with their nondominant side. Before and
      after the training period, a test was administered to determine the improvement
      in skill. Participants were asked to open and close the hand on 3 different
      velocities at command. MAIN OUTCOME MEASURES: Peak velocity, mean velocity, and
      number of peaks in the myoelectric signal of hand opening and closing. RESULTS:
      No differences were found for the different types of training; all participants
      learned to control the myoelectric hand. However, differences in learning
      abilities were revealed. After learning, a subgroup of the participants could
      produce clearly distinct myoelectric signals, which resulted in the ability to
      open and close the hand at 3 different speeds, whereas others could not produce
      distinct myoelectric signals. CONCLUSIONS: Acquired control of a myoelectric hand
      is irrespective of the type of training. Prosthetic users may differ in learning
      capacity; this should be taken into account when choosing the appropriate type of
      control for each patient.

PMID- 20801266
TI  - Minimal detectable change in quadriceps strength and voluntary muscle activation
      in patients with knee osteoarthritis.
AB  - OBJECTIVE: To examine the test-retest reliability and quantify the minimal
      detectable change (MDC) in quadriceps strength and voluntary activation in
      patients with knee osteoarthritis (OA). DESIGN: Repeated measures over a 1-week
      interval. SETTING: Tertiary care center. PARTICIPANTS: A convenience sample of
      patients (N=20) diagnosed with knee OA. INTERVENTION: Isokinetic and isometric
      quadriceps strength testing and voluntary quadriceps activation testing using
      interpolated twitch technique. MAIN OUTCOME MEASURES: Peak isokinetic and
      isometric knee extension torque (Nm) and percentage of voluntary quadriceps
      activation (%). RESULTS: The mean differences with 95% confidence intervals
      between the 2 test sessions for quadriceps isokinetic strength, isometric
      strength, and percent of voluntary activation were -4.34Nm (-14.01 to 5.34Nm),
      1.56Nm (-5.56 to 8.68Nm), and 1.34% (-.53 to 3.22%), respectively. The intraclass
      correlation coefficients for all measures ranged from .93 to .98. The standard
      errors of measurement (SEMs) for quadriceps isokinetic and isometric strength
      were 14.57Nm and 10.76Nm, respectively. The SEM for percentage of voluntary
      activation was 2.84%. Based on these values, the MDCs were 33.90Nm, 25.02Nm, and
      6.60% for quadriceps isokinetic strength, isometric strength, and percentage of
      voluntary activation, respectively. CONCLUSIONS: Maximal quadriceps isokinetic
      strength, isometric strength, and percentage of voluntary activation measures
      demonstrate excellent test-retest reliability in patients with knee OA. In
      addition to research applications, the present findings suggest these measures
      are appropriate for use when evaluating change in neuromuscular function of the
      quadriceps in individual patients.

PMID- 20801267
TI  - Diagnostic accuracy of history taking and physical examination for assessing
      anterior cruciate ligament lesions of the knee in primary care.
AB  - OBJECTIVE: To assess the diagnostic accuracy of history taking and physical
      examination for assessing anterior cruciate ligament (ACL) lesions in primary
      care. DESIGN: Cross-sectional diagnostic study. SETTING: Primary care.
      PARTICIPANTS: Patients (N=134; age, 18-65y) who consulted their general
      practitioner (GP) within 5 weeks after injury. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Index tests were obtained with a questionnaire and
      physical examination. Magnetic resonance imaging (MRI) was used as the reference
      test. Logistic regression analysis was used to determine associations with ACL
      lesions. Diagnostic accuracy was determined by calculating sensitivity (Se),
      specificity (Sp), predictive values, and likelihood ratio (LR). RESULTS: MRI
      showed an ACL lesion in 28 of 134 included patients. "Effusion," "popping
      sensation," "giving way," and "anterior drawer test (ADT)" showed associations
      with an ACL lesion (P<.05). Popping sensation showed Se, Sp, positive predictive
      value (PPV), and positive LR (LR(+)) of .63, .73, .39, and 2.3, respectively.
      Combining determinants from history taking (2 of 3 positive results regarding
      effusion, popping sensation, and giving way) improved diagnostic accuracy (Se,
      .71; Sp, .71; PPV, .42; and LR(+), 2.5). The ADT added diagnostic accuracy to
      these combinations (Se, .63; Sp, .85; PPV, .52; and LR(+), 4.2). CONCLUSIONS: ACL
      lesions are seen frequently. Based on history taking (effusion, popping
      sensation, and/or giving way) and physical examination (ADT), GPs can screen for
      ACL lesions in primary care.

PMID- 20801268
TI  - Effect of pulmonary rehabilitation on balance in persons with chronic obstructive
      pulmonary disease.
AB  - OBJECTIVES: To describe within-subject effects of pulmonary rehabilitation (PR)
      on balance in persons with chronic obstructive pulmonary disease (COPD) and to
      determine whether any observed changes in balance were associated with change in
      exercise tolerance or health-related quality of life. DESIGN: Single-arm
      longitudinal study. SETTING: Inpatient PR center. PARTICIPANTS: Subjects with
      COPD (N=29; mean +/- SD age, 69.8+/-10.3y; forced expiratory volume in 1 second,
      46.3%+/-22.3% predicted; 59% men [n=17]). INTERVENTIONS: A standardized 6-week
      multidisciplinary PR program (exercise training, breathing exercises, education,
      and psychologic support). MAIN OUTCOME MEASURES: Balance was assessed using the
      Berg Balance Scale (BBS), Timed Up and Go (TUG) test, and the Activities-Specific
      Balance Confidence (ABC) scale. Exercise tolerance was determined from the 6
      minute walk test (6MWT), and health-related quality of life from the Chronic
      Respiratory Questionnaire (CRQ). RESULTS: Subjects showed small improvements in
      BBS (2.8+/-2.8 points; P<.001) and TUG (-1.5+/-2.4s; P=.003) scores, but not in
      ABC scores (4.8+/-15.4 points; P>.05). There was a weak relationship between
      change in BBS and change in CRQ scores (r=.40; P=.045) and no relationship with
      change in 6MWT. CONCLUSIONS: PR contributed to minor improvements in balance and
      had no effect on balance confidence in subjects with COPD. Further work is
      warranted to determine the optimal intervention for improving balance in this
      population.

PMID- 20801269
TI  - Inspiratory muscle training for patients with chronic obstructive pulmonary
      disease: a practical guide for clinicians.
AB  - Reduced inspiratory muscle strength is common in people with chronic obstructive
      pulmonary disease (COPD) and is associated with dyspnea and decreased exercise
      capacity. Most studies of inspiratory muscle training (IMT) in COPD have
      demonstrated increased inspiratory muscle strength. Many have also shown
      improvements in dyspnea and exercise capacity. However, a persisting challenge
      when translating and applying the findings of these studies in clinical practice
      is the disparity in training loads, modalities, and outcomes measures used in the
      different studies. This commentary summarizes our clinical and research
      experience with a threshold IMT device with the aim of providing clinicians
      interested in prescribing IMT in this population with practical recommendations
      regarding patient selection, assessment, and implementation of training. We
      propose using an interval-based high-intensity threshold IMT program for people
      who are unable to participate fully in whole-body exercise training because of
      comorbidities such as severe musculoskeletal problems. Initial training loads
      equivalent to at least 30% of a person's maximum inspiratory pressure (PImax) are
      required for all people undertaking IMT. Supervision, which includes monitoring
      of oxygen saturation throughout the first training session, is recommended, and
      patients are warned to expect transient delayed-onset muscle soreness, a
      consequence of muscle adaptation to an unaccustomed activity. We recommend
      training be undertaken 3 times a week for 8 weeks, with loads progressively
      increased as symptoms permit. It is prudent to exclude people at risk of
      pneumothorax or spontaneous rib fracture. Evaluation of IMT should include
      measures of PImax, dyspnea, health-related quality of life, and exercise
      capacity.

PMID- 20801270
TI  - Adverse events reported in progressive resistance strength training trials in
      older adults: 2 sides of a coin.
AB  - OBJECTIVES: To summarize adverse events reported in randomized controlled trials
      that applied progressive resistance strength training in older adults and to
      examine factors that might be associated with these events. DESIGN: After
      systematic searches of databases, 2 reviewers independently screened and
      extracted adverse event-related information from identified trials. SETTING: Not
      applicable. PARTICIPANTS: Older adults 60 years of age and above (N = 6700).
      INTERVENTION: Muscle strength training exercise that increases load gradually.
      MAIN OUTCOME MEASURES: Adverse events and reasons for dropout. Adverse events
      include any undesirable outcomes that may be directly related or unrelated to the
      intervention. RESULTS: Among 121 trials identified, 53 trials provided no
      comments about adverse events, 25 trials reported no adverse events occurred, and
      43 trials reported some types of adverse events. Most adverse events reported
      were musculoskeletal problems such as muscle strain or joint pain. Adverse events
      were reported more often in trials that recruited participants with certain
      health conditions, functional limitations, or sedentary lifestyle; in trials that
      applied high intensity; and in trials that were published after the 2001
      Consolidated Standards of Reporting Trials statement had been published. Reasons
      reported for dropout in 58 trials might be related to adverse events. The most
      frequent reasons for dropout were illness or medical problems. CONCLUSIONS:
      Adverse events may be underreported because there is no consensus on the
      definition. Reporting adverse events associated with progressive resistance
      strength training in older adults is informative for practitioners to translate
      clinical research to clinical practice by knowing both the benefits and risks.
      Future trials should clearly define adverse events and report them in the
      published article.

PMID- 20801271
TI  - No effects of whole-body vibration training on muscle strength and gait
      performance in persons with late effects of polio: a pilot study.
AB  - OBJECTIVE: To evaluate the feasibility and possible effects of whole-body
      vibration (WBV) training on muscle strength and gait performance in people with
      late effects of polio. DESIGN: A case-controlled pilot study with assessments
      before and after training. SETTING: A university hospital rehabilitation
      department. PARTICIPANTS: People (N=5; 3 men, 2 women; mean age, 64+/-6.7y;
      range, 55-71y) with clinically and electrophysiologically verified late effects
      of polio. INTERVENTIONS: All participants underwent 10 sessions of supervised WBV
      training (standing with knees flexed 40 degrees -55 degrees up to 60 seconds per
      repetition and 10 repetitions per session twice weekly for 5 weeks). MAIN OUTCOME
      MEASURES: Isokinetic and isometric knee muscle strength (dynamometer), and gait
      performance (Timed Up & Go, Comfortable Gait Speed, Fast Gait Speed, and six
      minute walk tests). RESULTS: All participants completed the 5 weeks of WBV
      training, with no discernible discomfort. No significant changes in knee muscle
      strength or gait performance were found after the WBV training period.
      CONCLUSIONS: This pilot study did not show any significant improvements in knee
      muscle strength and gait performance following a standard protocol of WBV
      training. Thus, the results do not lend support to WBV training for people with
      late effects of polio.

PMID- 20801272
TI  - The trouble with "body weight support" in treadmill training.

PMID- 20801274
TI  - Measurement of participation in rehabilitation research.
AB  - The Rehabilitation Research and Training Center on Measuring Rehabilitation
      Outcomes and Effectiveness sponsored a 2-day International Symposium on
      Measurement of Participation in Rehabilitation Research in October 2008 as a
      preconference to the annual meeting of the American Congress of Rehabilitation
      Medicine and the American Society of Neurorehabilitation. The aims of the
      symposium were to highlight the state of the art in the measurement of
      participation and discuss its utility as an outcome measure for persons with
      disabilities by examining the construct of participation and its measurement.
      Plenary presentations and group discussions were organized around 4 key issues:
      (1) conceptualization, (2) operationalization, (3) environmental influences, and
      (4) personal characteristics. The full set of symposium articles, including
      recommendations for future research, appears in this supplement to Archives of
      Physical Medicine and Rehabilitation.

PMID- 20801275
TI  - A comparative review of contemporary participation measures' psychometric
      properties and content coverage.
AB  - OBJECTIVES: To provide a review of contemporary participation measures'
      conceptual foundations, psychometric properties and linkage to the International
      Classification of Functioning, Disability and Health (ICF). DATA SOURCES: Major
      medical databases, including PubMed, Medline, PsychInfo, and CINAHL. STUDY
      SELECTION: Articles that described the psychometric properties of generic
      measures of adult participation published in English between 1998 and 2008 were
      included. DATA EXTRACTION: Two reviewers independently reviewed each measure
      using recognized quality criteria for health questionnaires. Individual items
      were linked to the ICF using established linking rules. DATA SYNTHESIS: Eight
      measures met the inclusion criteria: Impact on Participation and Autonomy, ICF
      Measure of Participation and Activities, Keele Assessment of Participation,
      Assessment of Life Habits, Participation Profile, Participation Survey/Mobility,
      Participation Scale, and the Participation Measure for Post-Acute Care. The
      selected measures were based primarily on the ICF and demonstrated moderate to
      good validity and reliability, but psychometric information was often incomplete.
      The most commonly addressed ICF domains were mobility; domestic life; social
      interactions; major life domains; and community, social, and civic life.
      CONCLUSIONS: This review provides tools--a detailed review of individual
      participation measures, a comparative table of the measures' psychometric
      properties, and ICF linkages-and a set of 3 guiding questions to help users
      select appropriate participation measures.

PMID- 20801276
TI  - Measurement of participation: intersecting person, task, and environment.
AB  - The goals of this article are to describe participation as a transaction and
      issues involved in measuring and intervening using this transactional approach;
      describe ecologic and systems-based theoretic approaches for conceptualizing
      person-task-environment transactions; and illustrate examples of an exploratory
      strategy, radar plots, as a clinical tool for rehabilitation professionals to
      show this interaction and use it to inform participation-focused interventions
      with people with disabilities in rehabilitation settings. Participation
      necessarily occurs at the intersection of what the person can do, wants to do,
      has the opportunity to do, and is not prevented from doing. It is a transaction
      that occurs at the nexus of the person-task-environment. Measurement of
      participation should capture this transactive nature. Radar plots are part of a
      group of graphic displays frequently referred to as exploratory data analysis. In
      situations in which theory is not well developed, exploratory techniques such as
      radar plots may hold promise as ways to explore better the relationship among
      variables. This article describes strengths and limitations of radar plots and
      presents an example with data from the Community Participation Database.

PMID- 20801277
TI  - Participation: the insider's perspective.
AB  - The insider-outsider distinction is discussed in the context of people with
      disabilities. Insiders to disability are likely to have different subjective
      responses to life situations than do those who experience disability as
      onlookers. The importance of including the insider's perspective is discussed
      with respect to assessing participation in terms of setting goals, evaluating
      programs, setting research agendas, and conducting needs assessments. In terms of
      incorporating the insider's subjective response to participation into assessment,
      it is argued that both importance and salience are required to reflect the
      person's values and goals fully. A review of a sample of currently used
      assessment approaches is provided with a focus on how each instrument either
      incorporates or fails to incorporate the insider's perspective on participation.
      A distinction is made between instruments that tap into the perspective of a
      specific person at the point of assessment versus those that substitute a
      perspective based on discussions by groups of insiders, such as emerges from
      focus groups.

PMID- 20801278
TI  - Applications of response shift theory and methods to participation measurement: a
      brief history of a young field.
AB  - Measurement of participation in people with disability can pose psychometric and
      conceptual challenges. Ambiguous or paradoxical findings can occur because of
      differences among people or changes within people regarding internal standards,
      values, or conceptualization of participation. These response shifts can affect
      standard psychometric indices, such as reliability and validity. We focus herein
      on the interpretation of patient-reported outcomes and, in particular, on the
      cognitive appraisal processes known as response shift. We present theoretical and
      conceptual distinctions building on response shift theory and other current
      developments in health-related quality of life research to inform participation
      measurement research. We discuss how response shifts can influence the
      interpretation of reliability, validity, and responsiveness of participation
      measures. We then discuss the evidence for the clinical significance of response
      shift phenomena and describe current design, statistical, and individualized
      approaches for detecting response shift phenomena.

PMID- 20801279
TI  - Intersection of participation and environmental factors: a complex interactive
      process.
AB  - The objective was to review contemporary and historical rehabilitation-focused
      literature on conceptualizations of the environment, broadly defined, and
      environmental measures. Data sources included historical nonempirical American
      based literature from 1935 to the present and descriptive and empirical
      rehabilitation articles worldwide, retrieved from computerized databases
      predominantly from past 10 years depicting a participation-environment
      association. Literature selection required relevance to 3 combined topics:
      physical disability rehabilitation, participation/community integration, and
      impact of environmental barriers and facilitators. The ultimate focus was on
      spinal cord injury for recent literature and measures reviewed. Data extraction
      was based on author-assessed relevance to both participation and environmental
      considerations. Nonempirical literature from last three quarters of a century
      suggests an environmental impact on participation, focusing on "person
      environment fit." Recent empirical evidence supports environmental contributions
      to participation, but the magnitude of the contribution is low. Despite the
      obvious theoretic impact of the environment, scientific demonstration of
      environmental contribution to participation restriction or facilitation has yet
      to be achieved. Participation-environment interaction could be illustrated better
      by (1) taking into account critical elements in environmental measures (eg,
      comprehensiveness of approach to environment, scales describing spectrum of
      environmental influence, subjective vs objective perspectives), (2) addressing
      the concept of participation in a dimension-specific approach, and (3) avoiding
      environmental features in construction of participation measures.

PMID- 20801280
TI  - Issues in the conceptualization and measurement of participation: an overview.
AB  - While participation is increasingly defined as the key outcome of rehabilitation,
      disagreements on and shortcomings in the definition, operationalization, and
      measurement of this concept abound and interfere with the progress of clinical
      services and research. This article explores a number of the major issues related
      to the quantification of participation and makes suggestions for new directions,
      using the following orienting questions: What is the definition of participation?
      Where is the border between Participation and Activity? Is there more to
      participation than performance? What domains should be included in a
      participation measure? What are the appropriate metrics in quantifying
      participation? How do we define adequate participation? How should participation
      be operationalized? What is the proper measurement model for participation
      instruments? How should we collect data on participation? How do we evaluate the
      quality of a participation instrument?

PMID- 20801281
TI  - Issues affecting the selection of participation measurement in outcomes research
      and clinical trials.
AB  - The ever-growing number of participation measures without consensus on which is
      best makes it difficult to determine which measure to use in rehabilitation
      research and clinical trials. In an effort to address issues affecting the
      selection of a participation measure for a specific research purpose, this
      article (1) outlines the types and characteristics of participation measures, (2)
      enumerates various uses of participation measures in disability and
      rehabilitation research, (3) discusses appropriate matching of the type of
      participation measure with the research task, and (4) offers recommendations for
      future participation research. Participation instruments vary in terms of their
      degree of participation specificity, the conceptual model that underlies their
      development, whether they include multiple domains or take a more global
      approach, the extent to which they are objective versus subjective, whether they
      use general population norms, who is the respondent, the method of item and scale
      development, and their psychometric properties. Participation measures are used
      in individual and population assessments, observational research, and
      interventional research. Selection of a participation measure for use in a
      specific study requires an understanding of the characteristics of available
      tools and the nature of the research design, but most importantly, it requires
      matching the instrument to the specific research question or hypothesis.
      Instruments assessing participation are currently appropriate as secondary
      outcomes in trials evaluating interventions targeting activity limitation, and
      they will become appropriate as primary outcomes when interventions are tested
      that target participation directly. It will be easier to apply participation
      measures appropriately to their many research uses once substantial progress is
      made in obtaining better participation measurements and consensus is reached
      about the best tools.

PMID- 20801283
TI  - Community participation: measurement issues with persons with deficits in
      executive functioning.
AB  - Deficits in executive functioning and self-regulation, which are characteristic
      of many rehabilitation populations, can interfere with the provision of accurate
      and reliable responses to surveys designed to measure psychosocial constructs,
      including community participation. Using the Cognitive Aspects of Survey
      Methodology paradigm, survey researchers have found that respondents proceed
      through 4 processes that draw heavily on executive functions: (1) question
      comprehension and interpretation, (2) retrieval of applicable information from
      memory, (3) integration of retrieved information to form a judgment, and (4)
      configuration or mapping of the judgment to the response choices. Respondents
      without cognitive deficits frequently make errors because of challenges to their
      executive functions; it should therefore be anticipated that persons with
      deficits in executive functions will have even greater difficulties providing
      consistent and accurate responses. Research with persons with executive
      functioning deficits that empirically evaluates the various strategies
      recommended by survey researchers is sorely needed. At a minimum, survey design
      and administration should take into account potential sources of error resulting
      from executive functioning deficits by testing and incorporating strategies for
      reducing error.

PMID- 20801282
TI  - Measuring participation: the Patient-Reported Outcomes Measurement Information
      System experience.
AB  - OBJECTIVES: To describe the lessons learned in the initial development of Patient
      Reported Outcomes Measurement Information System social function item banks.
      DESIGN: Development and testing of 2 item pools within a general population to
      create item banks that measure ability to participate and satisfaction with
      participation in social activities. SETTING: Administration via the Internet.
      PARTICIPANTS: General population members (N=956) of a national polling
      organization registry participated; data for 768 and 778 participants were used
      in the analysis. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Measures
      of ability to participate and satisfaction with participation in social
      activities. RESULTS: Fifty-six items measuring the ability to participate were
      essentially unidimensional but did not fit an item response theory model. As a
      result, item banks were not developed for these items. Of the 56 items measuring
      satisfaction with participation, 14 items measuring social roles and 12 items
      measuring discretionary activities were unidimensional and met item response
      theory model assumptions. Two 7-item short forms were also developed.
      CONCLUSIONS: Four lessons, mostly concerning item content, were learned in the
      development of banks measuring social function. These lessons led to item
      revisions that are being tested in subsequent studies.

PMID- 20801284
TI  - Issues in participation measurement in research and clinical applications.
AB  - This article summarizes the recommendations made by participants at the
      International Symposium on Measurement of Participation in Rehabilitation
      Research. We draw on presentations by researchers, clinicians, and consumers; a
      respondent panel; and small group discussions that included symposium faculty and
      participants. Breakout groups discussion questions focused on several key issues:
      What do we know about defining and measuring participation? What don't we know?
      What are the research barriers to defining and measuring participation? What are
      the research priorities to resolve these obstacles and develop better
      instruments? What are the organizations and opportunities to continue the work of
      this symposium? What are the major aspects of participation that should be
      measured? With what kinds of participation constructs do item response theory
      methods and clinimetric and other psychometric approaches fit? Do people form
      "types" of "participants" that can be categorized? Which person characteristics
      should be considered when evaluating differential item functioning? What cultural
      and physical features should be considered in measuring participation? What
      legacy measures could be used as an item pool to tap "participation?" Can a
      crosswalk unite "legacy" participation measures? Reporters summarized the
      subgroups' discussions, and then the larger group focused on shared concerns,
      which are summarized here.

PMID- 20801285
TI  - The role of endoscopy in the management of obscure GI bleeding.
AB  - This is one of a series of statements discussing the use of GI endoscopy in
      common clinical situations. The Standards of Practice Committee of the American
      Society for Gastrointestinal Endoscopy (ASGE) prepared this text. In preparing
      this guideline, we performed a search of the medical literature by using PubMed.
      Additional references were obtained from the bibliographies of the identified
      articles and from recommendations of expert consultants. Guidelines for
      appropriate use of endoscopy are based on a critical review of the available data
      and expert consensus at the time the guidelines were drafted. Further controlled
      clinical studies may be needed to clarify aspects of this guideline. This
      guideline may be revised as necessary to account for changes in technology, new
      data, or other aspects of clinical practice. The recommendations are based on
      reviewed studies and are graded on the strength of the supporting evidence (Table
      1).(1) The strength of individual recommendations is based both upon the
      aggregate evidence quality and an assessment of the anticipated benefits and
      harms. Weaker recommendations are indicated by phrases such as "we suggest,"
      whereas stronger recommendations are typically stated as "we recommend." This
      guideline is intended to be an educational device to provide information that may
      assist endoscopists in providing care to patients. This guideline is not a rule
      and should not be construed as establishing a legal standard of care or as
      encouraging, advocating, requiring, or discouraging any particular treatment.
      Clinical decisions in any particular case involve a complex analysis of the
      patient's condition and available courses of action. Therefore, clinical
      considerations may lead an endoscopist to take a course of action that varies
      from these guidelines.

PMID- 20801286
TI  - Endoscopic therapy of obesity: a new paradigm in bariatric care.

PMID- 20801287
TI  - Distal pancreatectomy: another indication for prophylactic pancreatic stenting?

PMID- 20801288
TI  - Not everything is celiac disease.

PMID- 20801289
TI  - Narrow-band imaging for colorectal polyps: it can be taught but will it be used?

PMID- 20801290
TI  - The benefits of a gastroenterology fellows club.

PMID- 20801291
TI  - Erupted cysts in the cervical esophagus result in gastric inlet patches.

PMID- 20801292
TI  - Confocal laser endomicroscopy in Barrett's esophagus and endoscopically
      inapparent Barrett's neoplasia: a prospective, randomized, double-blind,
      controlled, crossover trial.

PMID- 20801293
TI  - "Locked" pancreatic duct-wire technique for biliary cannulation.

PMID- 20801295
TI  - Using an overtube for cholangioscopy.

PMID- 20801296
TI  - Does the selective use of metoclopramide improve the completion rate of small
      bowel capsule endoscopy?

PMID- 20801298
TI  - Ongoing colorectal cancer risk despite surveillance colonoscopy: the Polyp
      Prevention Trial Continued Follow-up Study.

PMID- 20801300
TI  - Problems with combining esophagogastroduodenoscopy and colonoscopy to analyze
      risks of transient hypoxia from procedures in patients with risk factors for
      obstructive sleep apnea: a call for stratifying risks according to individual
      procedures.

PMID- 20801302
TI  - Analytical methods for estimation of organophosphorus pesticide residues in
      fruits and vegetables: a review.
AB  - Use of pesticides has turned out to be an obligatory input to agriculture and
      public health. Versatile use of pesticides had resulted in contamination of all
      basic necessities of life, i.e. air, water and food. Among various pesticides,
      organophosphorus pesticides (OPPs), derivative of phosphoric acid, are the most
      extensively used insecticides or acaricides in many crops. Due to low persistency
      and high killing efficiency of OPPs, many agriculturalists regularly use this
      group of pesticides for various vegetables and fruits crops. The continuous use
      of pesticides has caused the deleterious effects to ecosystem. In response to
      this, a number of methods have been developed by several regulatory agencies and
      private laboratories and are applied routinely for the quantification and
      monitoring of multi pesticide residues in vegetables and crops. The present
      review pertains to various extraction and quantification procedures used world
      wide to analyze OPPs residues in various vegetables and fruits.

PMID- 20801303
TI  - Chromatographic and electrophoretic techniques used in the analysis of triazole
      antifungal agents-a review.
AB  - Systematic review of literature coupled with integrative research of published
      data for triazole antifungal agents was done. The investigated literature covered
      chromatographic and electrophoretic methods developed in the last 10 years (2000
      2009). The aim of this review was to compare different methodologies, assess
      preferences in the selection of analytical methods and to find still existing
      analytical problems. Last decade is characterized by dynamic development of
      instrumental methods, that results in advance and diversity of applied analytical
      procedures. The main focus was given to high-performance liquid chromatography
      (HPLC), the technique of choice in the analysis of most of pharmaceuticals. The
      review includes literature on 8 triazole antifungal drugs: fluconazole,
      itraconazole and terconazole from the first generation and posaconazole,
      voriconazole, ravuconazole, isavuconazole and albaconazole classified in second
      generation. Investigations of pharmaceutical formulations and biological samples
      were considered.

PMID- 20801304
TI  - Analysis of microcystins by capillary zone electrophoresis coupling with
      electrospray ionization mass spectrometry.
AB  - In this paper, a rapid and effective method based on capillary zone
      electrophoresis (CZE) coupled with electrospray ionization mass spectrometry (ESI
      MS) was established for the trace analysis of microcystin (MC) isomers in crude
      algae sample. The experimental conditions including the composition, acidity and
      concentration of buffer, separation voltage, injection time, and MS detection
      parameters were investigated in detail. A capillary separation system was as
      follows: a uncoated fused-silica capillary tube (50 microm i.d. x 90 cm), 40 mmol
      L(-1) ammonium acetate solution (pH 9.86) as running buffer, 25 kV as separation
      voltage, 20 kV x 3s water first and 20 kV x 20s for sample injection. Mass
      analysis was performed in ESI source, with sheath gas temperature 150 degrees C,
      sheath gas pressure 10 psi, and sheath gas flow 6 L min(-1). And sheath liquid
      was 7.5 mmol L(-1) acetic acid in 50% isopropanol-water (3 microg L min(-1)).
      Protonation and ammonium adduct molecular ions m/z 506.9 (MC-LR) and 532.0 (MC
      YR) were used for the quantification of MCs. Under these conditions, two MCs were
      baseline separated within 9 min, the calibration curves were obtained in the
      range of 0.11-10.0 microg mL(-1) and 0.16-10.5 microg mL(-1) for MC-LR and MC-YR,
      respectively. Meanwhile, limits of detection were 0.05 and 0.08 microg mL(-1) for
      MC-LR and MC-YR, respectively. The recoveries for the two MCs were in the range
      of 95.8-108%. The developed approach had been successfully applied to the
      analysis of MCs in crude algae samples.

PMID- 20801305
TI  - An all-solid-state monohydrogen phosphate sensor based on a macrocyclic
      ionophore.
AB  - An all-solid-state electrode, containing a synthesized chiral A(2)B(2)
      macrocyclic compound namely (4R,5R,15R,16R)-4,5,15,16-tetraphenyl-3,6,14,17
      tetraazatricyclo [13.3.1.18,12] tetracosa-1(23),8,10,12(24)19,21-hexaene
      2,7,13,18-tetrone as an ionophore in polyvinyl chloride (PVC)/polyurethane (PU)
      membrane matrix, has been developed for the selective quantification of
      monohydrogen phosphate ions. The best performing membrane contained PVC, PU,
      ionophore, and nitrophenyl octyl ether as a plasticizer in the ratio
      32.2:2.6:65.1 (w/w, %). It exhibited a near-Nernstian slope of 31.0+/-1.0
      mV/decade of activity for HPO(4)(2-) ions in the concentration range of 1. 10(-6)
      to 1.0 x 10(-2)M at pH 7.4. The detection limit of the electrode was 8.4 x 10(
      7)M and the life time was six weeks. The electrode displayed excellent
      selectivity for monohydrogen phosphate over other anions and the selectivity
      sequence was determined as HPO(4)(2-)>SO(4)(2-)>Ac(-)>NO(3)(-)>ClO(4)(-)>Cl(-)>I(
      ). The selective electrode for the monohydrogen phosphate ions was evaluated with
      a standard reference material (SRM 1548) and the titration of the sample
      solution.

PMID- 20801306
TI  - A sensitive immunoassay based on direct hapten coated format and biotin
      streptavidin system for the detection of chloramphenicol.
AB  - A novel enzyme liked immunosorbent assay (ELISA) was developed for the detection
      of chloramphenicol (CAP). In this assay, the small molecular hapten (Hap) was
      directly coated on the surface of microtiter plates and biotin-streptavidin
      system (BSAS) was employed to improve the sensitivity of immunoassay (BSAS-direct
      Hap coated ELISA). The surface of microtiter plates was treated with
      glutaraldehyde (GA) polymer network to introduce aldehyde group, which was used
      to cross-link with amino group of CAP. Compared with conventional ELISA (the
      plates were coated with Hap-carrier protein conjugates), the modified plates
      presented significantly high antibody and antigen (Ab-Ag) affinity and showed
      excellent stability. And then the biotinylated monoclonal antibody (mAb) and HRP
      labeled streptavidin were employed in this assay for amplification of signals.
      The sensitivity of BSAS-direct Hap coated ELISA was increased by approximately 20
      folds and the stability was also improved greatly compared to conventional ELISA.
      Its 50% inhibition concentration (IC(50)) for CAP was 10.5 ng mL(-1) and the
      limit of detection (LOD) was 0.2 ng mL(-1) after optimization of reaction
      conditions. To our knowledge, this was one of the most sensitive immunoassay for
      CAP yet reported. In sample analysis, the results of CAP detected by this assay
      were in accordance with which obtained by conventional ELISA and high performance
      liquid chromatography (HPLC). Therefore, it is an attractive alternative compared
      to conventional immunoassays in routine supervision for residue detection in food
      and environment.

PMID- 20801307
TI  - An i-DNA based electrochemical sensor for proton detection.
AB  - An i-DNA based electrochemical proton sensor which is fabricated by attaching the
      ferrocene-labeled i-DNA (Fc-i-DNA) onto a gold electrode is reported. This type
      of i-DNA is a cytidine-rich single-stranded oligonucleotide that its conformation
      can be switched between the random coil conformation and the folded i-motif
      structure at different pH values. The Fc-i-DNA is thiol terminated and can be
      bound to the gold electrode surface by Au-S interaction. With the variation of
      solution pH, the distance between ferrocene moiety and electrode surface is
      changed, leading to different redox currents. The pH can then be determined by
      measurement of the corresponding currents. In the range of pH 5.6-7.1, it is
      shown a linear relationship between the currents and pH values. The proton sensor
      also exhibits quick response, easy fabrication, and good selectivity.

PMID- 20801308
TI  - Nickel oxide nanotubes-carbon microparticles/Nafion nanocomposite for the
      electrooxidation and sensitive detection of metformin.
AB  - The electrocatalytic oxidation of metformin was studied on a nickel oxide
      nanotubes-carbon microparticles/Nafion nanocomposite, using cyclic voltammetry
      and chronoamperometry. In the presence of metformin, the anodic peak current of
      the Ni(II)/Ni(III) transition increased, followed by a decrease in the
      corresponding cathodic currents. Based on the results, the drug was oxidized on
      nickel oxide nanotubes via an electrocatalytic mechanism. The catalytic rate
      constant, the electron transfer coefficient and the diffusion coefficient
      involved in the electrocatalytic oxidation of the drug were reported. A sensitive
      and efficient amperometric method was presented for the analysis of the drug, and
      the corresponding analytical parameters were reported. For metformin, a detection
      limit of 0.45 micromol L(-1) was obtained. The proposed amperometric method was
      also applied to the analysis of commercial tablets and the results were in good
      agreement with the declared values. Also, the applicability of the method to the
      direct assays of the drug in human serum and urine and breast milk was described.

PMID- 20801309
TI  - Comparative studies on Tb (III)-selective PVC membrane sensors.
AB  - A new terbium selective sensor based on N-(2-hydroxyphenyl)-3-(2
      hydroxyphenylhydroxyphenylimino)-N-phenylbutanamidine (L(1)) and N,N'-bis((1H
      indole-3-yl)methylene)butane-1,4 diamine (L(2)) as a ionophore is reported.
      Effect of various plasticizers; 2-nitrophenyloctylether (o-NPOE), dibutyl
      butylphosphonate (DBBP), chloronaphthelene (CN), dioctylphthalate (DOP) and tri
      (2-ethylhexyl)phosphate (TEHP) with anion excluder, potassium tetrakis (p
      chloropheny1)borate (KTpClPB) have been studied. The membrane with a composition
      of ionophore (L(1)):KTpClPB:PVC:o-NPOE (w/w, %) in ratio of 3.0:5.0:30.0:62.0
      exhibited enhanced selectivity towards terbium ions (III) in the concentration
      range of 3.5 x 10(-7) to 1.0x10(-2)M with a detection limit of 1.2 x 10(-7)M and
      a Nernstian slope (20.0+/-0.5mVdec(-1) activity). The sensors showed the working
      pH range to be 3.5-7.5 with response time of 11s. The sensor has been found to
      work satisfactorily in partially non-aqueous media up to 15% (v/v) content of
      methanol, ethanol or acetonitrile and could be used for a period of 3 months. The
      selectivity coefficients indicated high selectivity for terbium (III). The fast
      and stable response, good reproducibility and long-term stability of the sensors
      were observed. The application of the sensor has been demonstrated in
      determination of terbium (III) ions in spiked water samples.

PMID- 20801310
TI  - Accurate determination of arsenic in arsenobetaine standard solutions of BCR-626
      and NMIJ CRM 7901-a by neutron activation analysis coupled with internal standard
      method.
AB  - Neutron activation analysis (NAA) coupled with an internal standard method was
      applied for the determination of As in the certified reference material (CRM) of
      arsenobetaine (AB) standard solutions to verify their certified values. Gold was
      used as an internal standard to compensate for the difference of the neutron
      exposure in an irradiation capsule and to improve the sample-to-sample
      repeatability. Application of the internal standard method significantly improved
      linearity of the calibration curve up to 1 microg of As, too. The analytical
      reliability of the proposed method was evaluated by k(0)-standardization NAA. The
      analytical results of As in AB standard solutions of BCR-626 and NMIJ CRM 7901-a
      were (499+/-55)mgkg(-1) (k=2) and (10.16+/-0.15)mgkg(-1) (k=2), respectively.
      These values were found to be 15-20% higher than the certified values. The
      between-bottle variation of BCR-626 was much larger than the expanded uncertainty
      of the certified value, although that of NMIJ CRM 7901-a was almost negligible.

PMID- 20801312
TI  - Mathematical modeling of a Nafion membrane based optode incorporating 1-(2'
      pyridylazo)-2-naphthol under flow injection conditions.
AB  - A general mathematical model of a flow-through optical chemical sensor prepared
      by the immobilization of 1-(2'-pyridylazo)-2-naphthol (PAN) into a commercial
      Nafion membrane was developed. The model takes into account the preparation of
      the optode membrane and in our opinion the most important chemical and physical
      processes involved in the generation of the analytical signal. The following
      model parameters were determined separately from the experimental verification of
      the model: aqueous diffusion coefficient of CuSO(4) - 8.75 x 10(-10)m(2)s(-1);
      membrane self-diffusion coefficient of the Cu(2+)-PAN complex and Cu(2+) - 1.87 x
      10(-16) and 6.00 x 10(-15)m(2)s(-1), respectively; Nafion/water ion-exchange
      equilibrium constants for the Cu(2+)-PAN complex and Cu(2+) - 109.2 and 3.65 x
      10(-3), respectively. Very good agreement was obtained between the experimental
      optode response and the model predictions thus showing that the model developed
      could be used successfully for the mathematical description and optimization of
      the PAN/Nafion optode as well as of other ion-exchange membrane based optodes
      having a similar response mechanism.

PMID- 20801311
TI  - Oxidation and flow-injection amperometric determination of 5-hydroxytryptophan at
      an electrode modified by electrochemically assisted deposition of a sol-gel film
      with templated nanoscale pores.
AB  - The oxidation of 5-hydroxytryptophan (5-HTPP) yielded a passivating polymeric
      film at an indium tin oxide (ITO) electrode. Coating ITO with a nanoscale sol-gel
      film with a mesoporous structure was shown to change the pathway of the chemical
      reaction coupled to the electron transfer. The sol-gel film was deposited by an
      electrochemically assisted process, and the mesoporosity was imparted by
      including generation-4 poly(amidoamine) dendrimer in the precursor solution. The
      dendrimer was removed subsequently with an atmospheric oxygen plasma. This
      electrode remained active during cyclic voltammetry and controlled potential
      electrolysis of 5-HTPP, which was attributed to dimer, rather than polymer,
      formation from the oxidation product. Mass spectrometry confirmed this
      hypothesis. The anodic current was limited by the electron-transfer kinetics.
      Modification of the sol-gel film by inclusion of cobalt hexacyanoferrate, which
      catalyzes the oxidation, resulted in a diffusion-limited current. Determination
      of 5-HTPP by flow-injection amperometry had a detection limit of 17nM.

PMID- 20801313
TI  - Direct electrochemistry of cytochrome c immobilized on a novel macroporous gold
      film coated with a self-assembled 11-mercaptoundecanoic acid monolayer.
AB  - We have successfully constructed a novel gold film with open interconnected
      macroporous walls of nanoparticles by combining the hydrogen bubble dynamic
      template synthesis with galvanic replacement reaction. After modified by a self
      assembled monolayer (SAM) of 11-mercaptoundecanoic acid (MUA), the three
      dimensionally (3D) interconnected macroporous Au film has been used as a
      biocompatible substrate for the immobilization of cytochrome c. The morphology,
      structure and electrochemical features of the modified and unmodified macroporous
      Au films were characterized by field-emission scanning electron microscopy
      (FESEM), energy-dispersive X-ray (EDX), cyclic voltammetry (CV) and
      electrochemical impedance spectroscopy (EIS). The results reveal that the
      resultant films had a large electroactive surface area for high protein loading,
      enhanced electron transfer of cytochrome c, retained electrochemical activity,
      good stability and repeatability. And the excellent electrochemical behaviors
      could be attributed to the hierarchical structure of the macroporous Au film
      constructed by nanoparticles.

PMID- 20801314
TI  - Immobilized capillary adenosine deaminase microreactor for inhibitor screening in
      natural extracts by capillary electrophoresis.
AB  - A novel strategy for the preparation of in-column adenosine deaminase (ADA)
      microreactor and rapid screening of enzyme inhibitors in natural extracts was
      demonstrated. In this approach, ADA was encapsulated in anionic polyelectrolyte
      alginate that was immobilized on the surface of fused-silica capillary via ionic
      binding technique with cationic polyelectrolyte polyethylenimine (PEI). On-line
      enzyme inhibition study was performed by capillary electrophoresis (CE). The
      substrate and product were baselined separated within 75s. The enzyme activity
      was determined by the quantification of peak area of the product. Enzyme
      inhibition can be read out directly from the reduced peak area of the product in
      comparison with a reference electropherogram obtained in the absence of any
      inhibitor. The inhibition percentage was used to evaluate relative activity of
      ADA microreactor. A known ADA inhibitor, erythro-9-(2-hydroxy-3-nonyl) adenine
      (EHNA) was employed as a model compound for the validation of the inhibitor
      screening method, and the screening of ADA inhibitor in 19 traditional Chinese
      herbal medicines was performed.

PMID- 20801315
TI  - Conductive three-dimensional ordered nano-gold film: ultrasensitive
      electrochemical sensing platform for clinical immunoassay.
AB  - A simple, reusable and ultrasensitive electrochemical clinic immunoassay is
      proposed via developing a versatile CTDONG (conductive three-dimensional ordered
      nano-gold) film-modified gold electrode, in which ferrocene derivative and human
      immunoglobulin G (hIgG) are used as signaling probe and model molecule,
      respectively. A signal-on signaling mechanism is achieved by utilizing a sandwich
      format of the primary antibody/hIgG/the secondary antibody labeled with Ferrocene
      (PAb/Ag/SAb). Owing to the combination of the advantages of CTDONG film with the
      versatility of ferrocene derivatives, a substantially enhanced signal accompanied
      by a low background peak current is achieved. By this sensing scheme, target
      molecule can be readily quantified in a comparatively wide dynamic range (8.1 x
      10(-13)-6.2 x 10(-10)M) with a relatively low detection limit (2.7 x 10(-13)M).
      In addition to a greatly improved signal gain, this immunosensor gives a
      favourable reusability and good reproducibility. Moreover, the CTDONG film-based
      sensing interface shows excellent anti-interference ability to the coexistent
      proteins. Meanwhile, the recovery test and determination of target molecule in
      real samples have confirmed the feasibility of designed sensing system for clinic
      immunoassay of protein molecules, demonstrating the potential application of
      described CTDONG film in the development of biomolecule assay platforms.

PMID- 20801316
TI  - Fast determination of chlorogenic acid in tobacco residues using microwave
      assisted extraction and capillary zone electrophoresis technique.
AB  - In this work, for the first time, capillary zone electrophoresis (CZE) technique
      combined with microwave-assisted extraction (MAE) was developed for the fast
      quantification of chlorogenic acid (CA) in tobacco residues. CA in tobacco
      residue samples were extracted by MAE technique, and then analyzed by CZE. As a
      new sample preparation method for tobacco residues, the MAE procedure is
      optimized, validated and compared with conventional methods including ultrasonic
      extraction (USE) and reflux extraction (RE). It is found that MAE gives the best
      result due to the highest extraction efficiency within shortest extraction time
      (only 4.0 min). Here, CA is determined by CZE based on the calibration curve of
      its authentic standard. The method linearity, detection limit, precision and
      recovery are studied. The results show that the combined MAE and CZE method has a
      linearity (R(2) 0.991, 0.003-0.5 mg ml(-1)), a limit of detection (0.003 mg ml(
      1)), a limit of quantification (0.01 mg ml(-1)), good precision (R.S.D.=4.28%)
      and a finer recovery (89.0%). The proposed method was successfully applied to the
      analysis of CA in tobacco residue samples. The experiment results have
      demonstrated that the CZE combined with MAE is a convenient, fast, economical and
      reliable method for the determination of CA in tobacco residues.

PMID- 20801317
TI  - A green method using micellar system for determination of sulfonamides in soil.
AB  - A green and simple method was developed for determination of sulfonamides (SAs)
      in soil samples. The procedure was based on the microwave-assisted extraction
      (MAE) of SAs from soil using non-ionic surfactant Triton X-114 as the extraction
      medium. Then sodium chloride was added into the MAE extract and the mixture was
      equilibrated for some time at high temperature. The analytes in the surfactant
      rich phase were concentrated with the help of centrifugation and directly
      analyzed by high performance liquid chromatography with UV detection. None of
      potentially hazardous organic solvents was used in the whole sample preparation
      procedure. The significant variables for the performance of extraction and
      concentration were studied. The limits of detection of SAs obtained are in the
      range of 3.2-5.7 ng g(-1). The relative standard deviations of intra- and inter
      day tests ranging from 3.5% to 7.7% and from 4.6% to 9.5% are obtained,
      respectively. This method was applied to the determination of SAs in some soil
      samples with different characteristics. The SAs recoveries obtained at fortified
      level of 100 ng g(-1) for these samples are in the range of 81.2-93.7%. The
      effect of ageing time of spiked soil samples on the SAs recoveries was examined
      by the proposed method and a method reported in the literature. The recoveries of
      SAs decreased when the ageing time changed from 1 day to 4 weeks.

PMID- 20801318
TI  - Electrocatalytic oxidation behavior of guanosine at graphene, chitosan and Fe3O4
      nanoparticles modified glassy carbon electrode and its determination.
AB  - A graphene, chitosan and Fe(3)O(4) nanoparticles (nano-Fe(3)O(4)) modified glassy
      carbon electrode (graphene-chitosan/nano-Fe(3)O(4)/GCE) was fabricated. The
      modified electrode was characterized by scanning electron microscope and
      electrochemical impedance spectroscopy. The electrochemical oxidation behavior of
      guanosine was investigated in pH 7.0 phosphate buffer solution by cyclic
      voltammetry and differential pulse voltammetry. The experimental results
      indicated that the modified electrode exhibited an electrocatalytic and
      adsorptive activities towards the oxidation of guanosine. The transfer electron
      number (n), transfer proton number (m) and electrochemically effective surface
      area (A) were calculated. Under the optimized conditions, the oxidation peak
      current was proportional to guanosine concentration in the range of 2.0 x 10(-6)
      to 3.5 x 10(-4) mol L(-1) with the correlation coefficient of 0.9939 and the
      detection limit of 7.5 x 10(-7) mol L(-1) (S/N=3). Moreover, the modified
      electrode showed good ability to discriminate the electrochemical oxidation
      response of guanosine, guanine and adenosine. The proposed method was further
      applied to determine guanosine in spiked urine samples and traditional Chinese
      medicines with satisfactory results.

PMID- 20801319
TI  - Structural elucidation of in vivo metabolites of phencynonate and its analogue
      thiencynonate in rats by HPLC-ESI-MSn.
AB  - The structural elucidation of the metabolites of phencynonate and its analogue
      thiencynonate in rats was performed by liquid chromatography-electrospray
      ionization tandem mass spectrometry (LC-ESI-MS(n)) in positive ion mode, by
      comparing their changes in molecular masses (DeltaM), retention times and
      spectral patterns with those of the parent drug. Phencynonate and thiencynonate
      were easily biotransformed in vivo by the pathways of N-demethylated, oxidative,
      hydroxylated and methoxylated to form seventeen metabolites that retained the
      some features of the two parent molecules. These metabolites included ten
      phencynonate metabolites (N-demethyphencynonate monoxide, N-demethyhydroxy
      phencynonate, phencynonate monoxide, hydroxyphencynonate, phencynonate dioxide,
      methoxyphencynonate, dihydroxyphencynonate, dihydroxyphencynonate, hydroxymethoxy
      phencynonate, trihydroxyphencynonate) and seven thiencynonate metabolites (N
      demethy thiencynonate, N-demethythiencynonate monoxide, N
      demethyhydroxythiencynonate, thiencynonate monoxide, hydroxythiencynonate,
      hydroxythiencynonate monoxide, dihydroxy thiencynonate). The described method has
      wide applicability to rapidly screen and provide structural information of these
      metabolites. The identifications of precise structures of these metabolites need
      to be confirmed by other techniques such as the (1)H and (13)C NMR.

PMID- 20801320
TI  - On-line solid-phase extraction-HPLC-fluorescence detection for simultaneous
      determination of puerarin and daidzein in human serum.
AB  - Response surface methodology (RSM) was applied to the optimization of on-line
      solid-phase extraction (SPE) parameters, and an automated system of on-line SPE
      coupled with high-performance liquid chromatography (HPLC) with fluorescence
      detection was developed for the determination of puerarin and daidzein in human
      serum. The human serum sample of 50 microL was injected into a conditioned C18
      SPE cartridge, and the matrix was washed out with acetonitrile-KH(2)PO(4)
      triethylamine buffer (0.01 M, pH 7.4) (3:97, v/v) for 3 min at a flow rate of
      0.25 mL/min. Then the target analytes were eluted and transferred to the
      analytical column. A chromatographic gradient elution was programmed with the
      mobile phase consisting of acetonitrile and KH(2)PO(4)-triethylamine buffer, and
      the analytes were determined with a fluorescence detector at excitation
      wavelength of 350 nm and emission wavelength of 472 nm, respectively. The
      proposed method presented good linear relations (0.85-170 microg/mL for puerarin
      and 0.2-40 microg/mL for daidzein), satisfactory precision (RSD<8%), and
      accredited recovery (92.5-107.8%).

PMID- 20801321
TI  - A novel electrochemical sensor based on nano-structured film electrode for
      monitoring nitric oxide in living tissues.
AB  - A sensor exhibited high sensitivity and good selectivity for determination of
      nitric oxide (NO) was fabricated. The sensor was constructured by coating
      Nafion/multi-walled carbon nanoubes-chitosan-gold nanoparticles (Nafion/MWNTs-CS
      AuNPs) film on glassy carbon electrode (GCE). Several key parameters affecting on
      the electrochemical response were optimized, such as the film thickness, applied
      potential and volume of Nafion. The sensor showed good linear relationship with
      the NO concentration in the range of 1.90 x 10(-8) to 5.40 x 10(-5)M and with the
      detection limit of 7.60 x 10(-9)M (S/N=3). Finally, the sensor was successfully
      applied to the monitoring of NO release from living tissues, including mouse
      kidney, heart, spleen and liver (a slice). NO release at micro-molar level can be
      detected while the NO donor l-arginine (l-Arg), nitroglycerin (GTN) and aspirin
      (ASA) was present. It was interestedly found that the capacities to induce NO
      generation were in the order of GTN>ASA>l-Arg when these stimulants were
      converted to the same concentration. In addition, the NO release is associated
      with the functional groups in these donors.

PMID- 20801322
TI  - Flow-injection determination of hydrogen peroxide based on fluorescence quenching
      of chromotropic acid catalyzed with Fe(II).
AB  - Flow-injection analysis system (FIA system), which was based on Fe(II)-catalyzed
      oxidation of chromotropic acid with hydrogen peroxide, was developed for the
      determination of hydrogen peroxide. The chromotropic acid has a fluorescence
      measured at lambda(em)=440 nm (emission wavelength) with lambda(ex)=235 nm
      (excitation wavelength), and the fluorescence intensity at lambda(em)=440 nm
      quietly decreased in the presence of hydrogen peroxide and Fe(II), which was
      caused by Fe(II)-catalyzed oxidation of chromotropic acid with hydrogen peroxide.
      By measuring the difference of fluorescence intensity, hydrogen peroxide (1.0 x
      10(-8)-1.0 x 10(-3) mol L(-1)) could be determined by the proposed FIA system,
      whose analytical throughput was 40 samples h(-1). The relative standard deviation
      (RSD) was 1.03% (n=10) for 4.0 x 10(-8) mol L(-1) hydrogen peroxide. The proposed
      FIA technique could be applied to the determination of hydrogen peroxide in rain
      water samples.

PMID- 20801323
TI  - Development and validation by accuracy profile of a method for the analysis of
      monoterpenes in indoor air by active sampling and thermal desorption-gas
      chromatography-mass spectrometry.
AB  - The technique of thermal desorption (TD)-GC/MS was evaluated for the measurement
      of monoterpenes in indoor air. The validation strategy was intentionally oriented
      towards routine use and the reliability of the method rather than extreme
      performance. For this reason, validation by accuracy profile was chosen. The
      accuracy profile procedure, which is based on the concept of total error
      (bias+standard deviation), guarantees that a known proportion of future results
      obtained with the method will be within acceptance limits. For all the compounds
      tested in the present study, alpha-pinene, alpha-terpineol, beta-pinene, d
      limonene, Delta(3)-carene, camphene, 1,8-cineole, p-cymene, linalool, but not in
      the case of carvone, the accuracy profile procedure established that at least 95%
      of the future results obtained would be within the +/-15% acceptance limits of
      the validated method over the whole defined concentration range. Other
      parameters, such as selectivity, recovery, repeatability, stability of the
      molecules of interest and the effect of temperature, were also determined. The
      performance of the described method was finally evaluated by the analysis of
      indoor air from new timber frame constructions.

PMID- 20801324
TI  - Preparation of a new 1,3-alternate-calix[4]arene-bonded HPLC stationary phase for
      the separation of phenols, aromatic amines and drugs.
AB  - We have synthesized the 1,3-alternate 25,27-dioctyloxy-26,28-bis-[3
      aminopropyloxy]-calix[4]arene and then immobilized onto gamma-chloropropylsilica
      gel (CPS). The high-performance liquid chromatographic behavior of some aromatic
      hydrocarbons, phenolic compounds, aromatic amines and drug compounds was studied
      on this 1,3-alternate-calix[4]arene-bonded silica gel stationary phase (CIMS).
      The effect of organic modifier content and pH of the mobile phase on retention
      and selectivity of these compounds were investigated. According to
      chromatographic data, it can be concluded that the selectivity of CIMS for
      analytes ascribes to various interactions between CIMS and the analytes, such as
      hydrophobic interaction, hydrogen bonding interaction, pi-pi interaction and
      inclusion interaction.

PMID- 20801325
TI  - Extraction and concentration of vapors from fire debris for forensic purposes:
      evaluation of the use of Radiello Passive Air Sampler.
AB  - The Radiello Passive Air Sampler is one of the latest innovations developed for
      the sampling of pollutants in the air by passive headspace. It has been reported
      that its properties allow an enhanced sensitivity, reproducibility and adsorption
      capacity. It therefore appears to be of interest in the extraction of potential
      residues of ignitable liquids present in fire debris when arson is suspected. A
      theoretical approach and several laboratory tests have made it possible to
      precisely characterize in a forensic perspective the potential of the device in
      extracting and concentrating the vapors of ignitable liquids found in fire
      debris. Despite some advantages, the Radiello device appears to be less efficient
      than traditional axial symmetry samplers.

PMID- 20801326
TI  - Partial least squares X-ray fluorescence determination of trace elements in
      sediments from the estuary of Nerbioi-Ibaizabal River.
AB  - The feasibility of partial least squares (PLS) regression modeling of X-ray
      fluorescence (XRF) spectra of estuarine sediments has been evaluated as a tool
      for rapid trace element content monitoring. Multivariate PLS calibration models
      were developed to predict the concentration of Al, As, Cd, Co, Cr, Cu, Fe, Mg,
      Mn, Ni, Pb, Sn, V and Zn in sediments collected from different locations across
      the estuary of the Nerbioi-Ibaizabal River (Metropolitan Bilbao, Bay of Biscay,
      Basque Country). The study was carried out on a set of 116 sediment samples,
      previously lyophilized and sieved with a particle size lower than 63 microm.
      Sample reference data were obtained by inductively coupled plasma mass
      spectrometry. 34 samples were selected for building PLS models through a
      hierarchical cluster analysis. The remaining 82 samples were used as a test set
      to validate the models. Results obtained in the present study involved relative
      root mean square errors of prediction varying from 21%, for the determination of
      Pb at hundreds microg g(-1) level, up to 87%, for Ni determination at little tens
      microg g(-1) level. An average prediction error of +/-37% for the 14 elements
      under study was obtained, being in all cases mean differences between predicted
      and reference results of the same order than the standard deviation of three
      replicates from a same sample. Residual predictive deviation values obtained
      ranged from 1.1 to 3.9.

PMID- 20801327
TI  - Elucidation of triacylglycerols in cod liver oil by liquid chromatography
      electrospray tandem ion-trap mass spectrometry.
AB  - Though liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS(2))
      has been widely used in the structural elucidation of triacylglycerols (TAG) in
      vegetable oils, its potentiality for the identification of TAG molecules in omega
      3 rich oils remains unexplored till date. Hence, this article investigates the
      applicability of LC-ESI-MS(2) for the structural characterization of naturally
      occurring TAG in cod liver oil without the TAG fractionation during the sample
      preparation. A computational algorithm was developed to automatically interpret
      the mass spectra and elucidate the TAG structures respectively. The results were
      compared against the lipase benchmark method. A principal component analysis
      study revealed that it is possible to discriminate genuine from adulterated cod
      liver oil.

PMID- 20801328
TI  - Development and application of UHPLC-MS/MS method for the determination of
      phenolic compounds in Chamomile flowers and Chamomile tea extracts.
AB  - UHPLC-MS/MS method using BEH C18 analytical column was developed for the
      separation and quantitation of 12 phenolic compounds of Chamomile (Matricaria
      recutita L.). The separation was accomplished using gradient elution with mobile
      phase consisting of methanol and formic acid 0.1%. ESI in both positive and
      negative ion mode was optimized with the aim to reach high sensitivity and
      selectivity for quantitation using SRM experiment. ESI in negative ion mode was
      found to be more convenient for quantitative analysis of all phenolics except of
      chlorogenic acid and kaempherol, which demonstrated better results of linearity,
      accuracy and precision in ESI positive ion mode. The results of method validation
      confirmed, that developed UHPLC-MS/MS method was convenient and reliable for the
      determination of phenolic compounds in Chamomile extracts with linearity >0.9982,
      accuracy within 76.7-126.7% and precision within 2.2-12.7% at three spiked
      concentration levels. Method sensitivity expressed as LOQ was typically 5-20
      nmol/l. Extracts of Chamomile flowers and Chamomile tea were subjected to UHPLC
      MS/MS analysis. The most abundant phenolic compounds in both Chamomile flowers
      and Chamomile tea extracts were chlorogenic acid, umbelliferone, apigenin and
      apigenin-7-glucoside. In Chamomile tea extracts there was greater abundance of
      flavonoid glycosides such as rutin or quercitrin, while the aglycone apigenin and
      its glycoside were present in lower amount.

PMID- 20801329
TI  - Determination of homocysteine thiolactone, reduced homocysteine, homocystine,
      homocysteine-cysteine mixed disulfide, cysteine and cystine in a reaction mixture
      by overimposed pressure/voltage capillary electrophoresis.
AB  - An elevated level of thiol amino acid homocysteine is associated with several
      complex disorders. Homocysteine ability to bind proteins, thereby modulating
      their structure and function, is proposed to be one of the mechanisms of
      homocysteine induced pathogenecity. Homocysteine and homocysteine thiolactone
      bind to protein cysteine and lysine residues respectively. A major hurdle in
      studying protein homocysteinylation is the lack of suitable analytical techniques
      to determine simultaneously the concentrations of reduced and oxidized forms of
      homocysteine and cysteine (especially homocysteine-cysteine mixed disulfide)
      together with thiolactone formed during the reaction of homocysteine or
      thiolactone with proteins. Herein we report a capillary electrophoresis method to
      determine simultaneously the levels of these intermediates. For this 40 mmol/L
      Tris phosphate buffer at (pH 1.60) was used as running electrolyte, and the
      separation was performed by the simultaneous application of a CE voltage of 15kV
      and an overimposed pressure of 0.1 psi. A rapid separation of these intermediates
      in less than 6 min with a good reproducibility of both peak areas (CV<2%) and
      migration time (CV<0.2%) was obtained. The applicability of our method was
      validated by incubating reduced homocysteine and albumin and measuring the
      reaction intermediates in the solution mixture.

PMID- 20801330
TI  - Sensitive determination of pesticides residues in wine samples with the aid of
      single-drop microextraction and response surface methodology.
AB  - The multi-residue trace-level determination of six pesticides (diazinon,
      dimethoate, chlorpyrifos, vinclozolin, fenthion and quinalphos) in wine samples,
      after their single-drop microextraction (SDME) is presented herein. The
      extraction procedure was optimized using the multivariate optimization approach
      following a two-stage process. The first screening experimental design brought
      out the significant parameters and was followed by a central composite design
      (CCD) experiment, which revealed the simultaneous effect of the significant
      factors affecting the SDME process. High level of linearity for all target
      analytes was recorded with r(2) ranging between 0.9978 and 0.9999 while
      repeatability (intra-day) and reproducibility (inter-day) varied from 5.6% to
      7.4% and 4.9% to 12.5%, respectively. Limits of detection (LODs) and limits of
      quantification (LOQs) were found to range in the low microg L(-1) level. In
      general, the developed methodology presented simplicity and enhanced sensitivity,
      rendering it appropriate for routine wine screening purposes.

PMID- 20801331
TI  - Simultaneous determination of fermented milk aroma compounds by a potentiometric
      sensor array.
AB  - The paper reports on the application of an electronic tongue for simultaneous
      determination of ethanol, acetaldehyde, diacetyl, lactic acid, acetic acid and
      citric acid content in probiotic fermented milk. The alphaAstree electronic
      tongue by Alpha M.O.S. was employed. The sensor array comprised of seven non
      specific, cross-sensitive sensors developed especially for food analysis coupled
      with a reference Ag/AgCl electrode. Samples of plain, strawberry, apple-pear and
      forest-fruit flavored probiotic fermented milk were analyzed both by standard
      methods and by the potentiometric sensor array. The results obtained by these
      methods were used for the development of neural network models for rapid
      estimation of aroma compounds content in probiotic fermented milk. The highest
      correlation (0.967) and lowest standard deviation of error for the training
      (0.585), selection (0.503) and testing (0.571) subset was obtained for the
      estimation of ethanol content. The lowest correlation (0.669) was obtained for
      the estimation of acetaldehyde content. The model exhibited poor performance in
      average error and standard deviations of errors in all subsets which could be
      explained by low sensitivity of the sensor array to the compound. The obtained
      results indicate that the potentiometric electronic tongue coupled with
      artificial neural networks can be applied as a rapid method for the determination
      of aroma compounds in probiotic fermented milk.

PMID- 20801332
TI  - Determination of diffusible and total hydrogen concentration in coated and
      uncoated steel using melt and solid extraction techniques: Part I.
AB  - It is essentially to know the bulk hydrogen concentration in various types of
      steel because it indicates the amount of hydrogen that can be trapped by the
      different alloys of steel. This information leads to more knowledge about the
      interactions of steel alloys with hydrogen containing environment and stability
      of the steel material during usage. To get this information precise analytical
      methods are necessary. Although the analytical methods for the determination of
      hydrogen in steel samples are often discussed, there are no sufficient systematic
      studies as far as the influence of the sample preparation on the analytical value
      is concerned. The influence of different sample preparation methods on the
      hydrogen determination in steel at parts per million levels by melting extracting
      methods has been investigated in this work. The hydrogen was measured by thermal
      conductivity and infrared detection. The flat sheet samples were zinc coated and
      uncoated ferritic types of steel. The zinc coating was removed by chemical (acid
      etching) and physical (paper scraping) methods. Dichloromethane acetone/ethanol,
      tetrachloromethane and alkaline steel cleaner (Ridoline C72) have been used for
      cleaning the surface of uncoated samples. The results of the total hydrogen
      content obtained by applying the different methods were evaluated.

PMID- 20801333
TI  - Enantioselective HPLC combined with spectroscopic methods: a valid strategy to
      determine the absolute configuration of potential beta-secretase inhibitors.
AB  - A direct HPLC enantioseparation of three representative compounds of a new family
      of potential non-peptide beta-secretase inhibitors was performed on the
      immobilized Chiralpak IA chiral stationary phase. Semipreparative amounts of
      enantiopure forms were collected and submitted to stereochemical
      characterization. The absolute configuration was assigned by a multi-step
      methodology based on the combination of Mosher's method with circular dichroism
      (CD) spectroscopy. The results from the NMR/CD study fully correlated the
      configurational assignment obtained by a second approach involving single crystal
      X-ray diffraction.

PMID- 20801334
TI  - A simple ion chromatography method for inorganic anion analysis in edible
      seaweeds.
AB  - A new, simple, fast and sensitive ion chromatography (IC) method, for the
      simultaneous analysis of fluoride, chloride, nitrite, bromide, nitrate, phosphate
      and sulphate in edible seaweeds was developed and reported for the first time.
      The validation of the analytical method was studied in terms of linearity,
      sensitivity, precision and accuracy. All standard calibration curves showed very
      good correlation between anion peak area and concentration (r>0.999). Limits of
      detection and quantitation ranged between 0.002-0.05 mg/L and 0.01-0.1mg/L,
      respectively and indicated the high sensitivity of the method. Relative standard
      deviation values of repeatability and inter-day precision for standard anions
      with the same sample were less than 2%. Anion recoveries ranged from 97 to 113%
      for chloride and from 87 to 105% for sulphate, respectively and showed the fairly
      good accuracy of the method. The method was applied to the analysis of inorganic
      anions in brown and red edible seaweeds. Brown seaweeds were characterized by
      higher chloride content up to 33.7-36.9%, while red seaweeds were characterized
      by higher sulphate content (45-57%). Sulphate content in seaweeds is related to
      the presence of sulphated polysaccharides of biological importance. The method
      developed was well applicable to mineral anion analysis in edible seaweeds and
      shows suitability and reliability of use in other food samples of nutritional
      importance.

PMID- 20801335
TI  - Determination of organic priority pollutants in sewage treatment plant effluents
      by gas chromatography high-resolution mass spectrometry.
AB  - In this work, we report the development and validation of an analytical method
      for the trace level determination of 14 selected (EU-directive) priority organic
      pollutants (namely, 1,2,3-trichlorobenzene (1,2,3-TCB), 1,2,4-trichlorobenzene,
      1,3,5-trichlorobenzene, hexachloro-1,3-butadiene, pentachlorobenzene,
      hexachlorobenzene, alachlor, alpha-hexachloro-cyclohexane (alpha-HCH), beta-HCH,
      gamma-HCH (lindane), delta-HCH, tetra-brominated diphenyl ether (tetra-BDE),
      penta-brominated diphenyl ether and hepta-brominated diphenyl ether) in
      wastewater samples from 5 different sewage treatment plants (STPs) located in
      Spain. The proposed methodology is based on liquid-liquid extraction with n
      hexane followed by identification and confirmation of the selected pollutants by
      gas chromatography high-resolution mass spectrometry in selected ion recording
      acquisition mode. Recovery studies performed with spiked wastewater samples at
      two different concentration levels (0.1 and 1 microg L(-1)) gave mean recoveries
      in the range 80-120% (except for trichlorobenzenes, ca. with 50%) with RSD values
      below 10% in most cases, thus confirming the usefulness of the proposed
      methodology for the analyses of this kind of complex samples. The obtained
      detection limits in effluent wastewater matrices were in the low nanogram per
      liter range, with values as low as 0.09 ng L(-1) for tetra-BDE and 0.3 ng L(-1)
      for hexachlorobenzene. Finally, the proposed methodology was successfully applied
      to a monitoring study intended to characterize wastewater effluents of 5
      different sewage treatment plants with different major activities (Industrial,
      Coastal, Urban). Most of the compounds targeted were detected in the ng L(-1)
      range at concentrations ranging from 0.19 ng L(-1) to 135 ng L(-1)
      (hexachlorobenzene).

PMID- 20801336
TI  - Comparison of action of mixed permanent chemical modifiers for cadmium and lead
      determination in sediments and soils by slurry sampling graphite furnace atomic
      absorption spectrometry.
AB  - Slurry sampling atomic absorption spectrometry with electrothermal atomization
      was used to the determination of cadmium (Cd) and lead (Pb) in soils and
      sediments using permanent modifiers. Comparison of action of mixed permanent
      modifiers niobium (Nb)/iridium (Ir) and tungsten (W)/iridium (Ir) were studied in
      detail. The effect of amount of Ir, W and Nb on analytical signals of Cd and Pb
      was examined. The optimal amounts of modifiers for Cd and Pb determination were
      stated. Niobium carbide formation on graphite surface was studied for different
      pyrolysis temperatures. Finally for Cd determination in sediments and soils 200
      microg of Nb mixed with 5 microg of Ir was used as permanent modifiers and 15
      microg of Nb mixed with 200 microg of Ir for Pb determination. Suspensions were
      prepared in 5% HNO(3). The analytical procedure was optimized carefully basing on
      data from pyrolysis and atomization curves studies. Ammonium dihydrogen phosphate
      was used additionally as matrix modifier during Cd determination in samples in
      order to prevent interferences coming from matrix components. The analysis of
      CRMs confirmed the reliability of the proposed approach. The precision and
      accuracy of Cd and Pb determination by the described method for soils and
      sediments were acceptable.

PMID- 20801337
TI  - High-performance affinity monolith chromatography for chiral separation and
      determination of enzyme kinetic constants.
AB  - A new kind of immobilized human serum albumin (HSA) column was developed by using
      the sub-micron skeletal polymer monolith based on poly(glycidyl methacrylate-co
      ethylene glycol dimethacrylate) [poly(GMA-EDMA)] as the support of high
      performance affinity chromatography. Using the epoxide functional groups
      presented in GMA, the HSA immobilization procedure was performed by two different
      means. The affinity columns were successfully adopted for the chiral separation
      of D,L-amino acids (AAs). Then this method was shown to be applicable to the
      quantitative analysis of D-tryptophan, with a linear range between 12.0 microM
      and 979.0 microM, and a correlation coefficient above 0.99. Furthermore, it was
      used for the analysis of urine sample. This assay is demonstrated to be facile
      and relatively rapid. So it allows us to measure the enzyme catalytic activity in
      the incubation of D,L-AAs with D-AA oxidase and to study the kinetics of the
      enzyme reaction. It implied that the affinity monolithic columns can be a useful
      tool for studying DAAO enzyme reaction and investigating the potential enzyme
      mechanism requirement among chiral conversion.

PMID- 20801338
TI  - Novel flexible chemical gas sensor based on poly(3,4-ethylenedioxythiophene)
      nanotube membrane.
AB  - Poly(3,4-ethylenedioxythiophene) nanotubes (PEDOT NTs) flexible membrane was
      successfully fabricated by vapor deposition polymerization (VDP) mediated
      electrospinning for ammonia gas detection. PVA nanofibers (NFs) were electrospun
      as a core part and polyvinyl alcohol (PVA)/PEDOT coaxial nanocables (NCs) were
      prepared by VDP method via EDOT monomer adsorption onto the electrospun PVA NFs
      as templates. To obtain the PEDOT NTs membrane, the PVA NFs were removed from
      PVA/PEDOT coaxial NCs with distilled water. PVA/PEDOT coaxial NCs and PEDOT NTs
      had the conductivities of 71 and 61 Scm(-1) and were applied as a transducer for
      ammonia gas detection in the range of 1-100 parts per million (ppm) of NH(3) gas.
      They exhibited the minimum detectable level of ca. 5 parts per million (ppm) and
      fast response time (less than 1s) towards ammonia gas. In a recovery time, the
      PEDOT NTs membrane sensor was ca. 30s and shorter compared to that of the
      membrane sensor based on the PVA/PEDOT NCs (ca. 50s). In addition, sensor
      performance of PEDOT NTs membrane was also undertaken as a function of membrane
      thickness. Thick membrane sensor (30 microm) had the enhanced sensitivity and the
      sensitivity on the membrane thickness was in the order of 30 microm>20 microm>10
      microm at 60 ppm of NH(3) gas.

PMID- 20801339
TI  - Direct electrochemistry-based hydrogen peroxide biosensor formed from single
      layer graphene nanoplatelet-enzyme composite film.
AB  - A novel electrochemical sensing system for direct electrochemistry-based hydrogen
      peroxide biosensor was developed that relied on the virtues of excellent
      biocompatibility, conductivity and high sensitivity to the local perturbations of
      single-layer graphene nanoplatelet (SLGnP). To demonstrate the concept, the
      horseradish peroxidase (HRP) enzyme was selected as a model to form the SLGnP-TPA
      (tetrasodium 1,3,6,8-pyrenetetrasulfonic acid)-HRP composite film. The single
      layer graphene composite film displayed a pair of well-defined and good
      reversible cyclic voltammetric peak for Fe(III)/Fe(II) redox couple of HRP,
      reflecting the enhancement for the direct electron transfer between the enzyme
      and the electrode surface. Analysis using electrochemical impedance spectroscopy
      (EIS) revealed that electrostatic attractions existed between graphene monolayers
      and enzyme molecules. The intimate graphene and enzyme interaction was also
      observed using scanning electron microscopy (SEM), which resulted in the special
      properties of the composite film. Ultraviolet visible spectroscopy (UV-vis)
      indicated the enzyme in the composite film retained its secondary structure
      similar to the native state. The composite film demonstrated excellent
      electrochemical responses for the electrocatalytic reduction of hydrogen peroxide
      (H(2)O(2)), thus suggesting its great potential applications in direct
      electrochemistry-based biosensors.

PMID- 20801340
TI  - The assessment of pi-pi selective stationary phases for two-dimensional HPLC
      analysis of foods: application to the analysis of coffee.
AB  - Differences between alkyl, dipole-dipole, hydrogen bonding, and pi-pi selective
      surfaces represented by non-resonance and resonance pi-stationary phases have
      been assessed for the separation of 'Ristretto' cafe espresso by employing 2DHPLC
      techniques with C18 phase selectivity detection. Geometric approach to factor
      analysis (GAFA) was used to measure the detected peaks (N), spreading angle
      (beta), correlation, practical peak capacity (n(p)) and percentage usage of the
      separations space, as an assessment of selectivity differences between regional
      quadrants of the two-dimensional separation plane. Although all tested systems
      were correlated to some degree to the C18 dimension, regional measurement of
      separation divergence revealed that performance of specific systems was better
      for certain sample components. The results illustrate that because of the
      complexity of the 'real' sample obtaining a truly orthogonal two-dimensional
      system for complex samples of natural origin may be practically impossible.

PMID- 20801341
TI  - The analysis of cafe espresso using two-dimensional reversed phase-reversed phase
      high performance liquid chromatography with UV-absorbance and chemiluminescence
      detection.
AB  - In this study, an activity based screening technique combining two-dimensional
      liquid chromatography (2DHPLC) with UV-absorbance and chemiluminescence detection
      was applied to study "Ristretto", "Decaffeinatto" and "Volluto" espresso coffees.
      This technique, which coupled the separation power of 2DHPLC with the sensitivity
      and selectivity of the chemiluminescence detection, offers great potential for
      screening complex samples for antioxidant compounds. Detailed information
      regarding the complexity of the sample, and the variation between these three
      coffees could be obtained using this multidimensional-hyphenated method of
      analysis.

PMID- 20801342
TI  - A four-electrode microconstant direct current resistance detector for ion
      chromatography applying ion-exchange membrane and porous electrode.
AB  - A four-electrode microconstant direct current resistance detector for ion
      chromatography not sensitive to the effects of electrode polarization,
      capacitance, and electrolysis by-products is proposed. A constant current of
      microampere magnitude is applied across the current electrodes of the four
      electrode device, and the voltage responses between the detection probes are
      directly picked up by a high input impedance instrumentation amplifier. The ion
      exchange membranes, which separate the detection chamber from the electrolysis
      chambers, enable the measurement of solution resistance free of the interference
      of electrolysis by-products. Two resin beds in the detection chamber serve as ion
      conductors while reduce the dead volume of the detector. Recycled detection
      effluent supplies water for the electrolysis reactions at the current electrodes
      to sustain constant current in solution. The porous detection probes provide
      microchannel for the flowing solution while indicating signals. Owing to the
      constant current excitation, the electronics setup becomes simple. The cell
      configuration, operating principle, electronics, and error analysis of this
      detection mode are discussed along with their use for suppressed anion
      chromatography. Experimental data show that this four-electrode direct current
      detection mode is comparable to conventional two-electrode alternating current
      method.

PMID- 20801343
TI  - Determination of phenylurea and triazine herbicides in milk by microwave assisted
      ionic liquid microextraction high-performance liquid chromatography.
AB  - The determination of phenylurea and triazine herbicides in milk based on
      microwave assisted ionic liquid microextraction (MAILME) coupled with high
      performance liquid chromatographic separation was described. The experimental
      parameters of the MAILE, including type and amount of ionic liquid, microwave
      extraction power, extraction time and salt concentration in sample, were
      evaluated by a univariate method and orthogonal screening. When 60 microL of
      [C(6)MIM][PF(6)] was used as extraction solvent the target compounds can be
      isolated from the 4 mL of milk. The MAILME is quick (7 min) and simple. The
      detection limits for isoproturon, monolinuron, linuron, propazine, prometryne,
      terbutryn and trietazine are 0.46, 0.78, 1.00, 1.21, 1.96, 0.84 and 1.28 microg
      L(-1), respectively. The proposed method was applied to the analysis of milk
      samples and the recoveries of the analytes ranged from 88.4 to 117.9% and
      relative standard deviations were lower than 7.43%.

PMID- 20801344
TI  - Direct separation of boron from Na- and Ca-rich matrices by sublimation for
      stable isotope measurement by MC-ICP-MS.
AB  - An improved technique for precise and accurate determination of boron isotopic
      composition in Na-rich natural waters (groundwater, seawater) and marine biogenic
      carbonates was developed. This study used a 'micro-sublimation' technique to
      separate B from natural sample matrices in place of the conventional ion-exchange
      extraction. By adjusting analyte to appropriate pH, quantitative recovery of
      boron can be achieved (>98%) and the B procedural blank is limited to <8 pg. An
      additional mass bias effect in MC-ICP-MS was observed which could not be improved
      via the standard-sample-standard bracketing or the 'pseudo internal'
      normalization by Li. Therefore a standard other than NBS SRM 951 was used to
      monitor plasma condition in order to maintain analytical accuracy. An isotope
      cross-calibration with results from TIMS shows that the space-charge mass bias on
      MC-ICP-MS can be successfully corrected using off-line mathematical manipulation.
      Several reference materials, including the seawater IAPSO and two groundwater
      standards IAEA-B-2 and IAEA-B-3, were used to validate this approach. We found
      that the delta(11)B of the reference coral JCp-1 was 24.22+/-0.28 per thousand,
      corresponding to seawater pH based on the coral delta(11)B-pH function.

PMID- 20801345
TI  - A 4-hydroxy-N'-[(E)-(2-hydroxyphenyl)methylidene]benzohydrazide-based sorbent
      material for the extraction-HPLC determination of biogenic amines in food
      samples.
AB  - A sorbent material based on a newly synthesized hydrazone ligand, 4-hydroxy-N'
      [(E)-(2-hydroxyphenyl)methylidene]benzohydrazide was prepared by immobilizing the
      ligand into a silica sol-gel matrix. The capability of the sorbent material for
      the extraction of seven biogenic amines (BAs), i.e., tryptamine (TRY), beta
      phenylethylamine (PEA), putrescine (PUT), cadaverine (CAD), histamine (HIS),
      tyramine (TYR), and spermidine (SPD) was studied. Under the adopted conditions,
      the sorbent showed good selectivity towards PUT, CAD, HIS and SPD (% extraction
      (%E)>96) while %E for TYR, TRY and PEA were 82.0, 78.9 and 46.4%, respectively.
      The sorbent could be used up to six extraction cycles for SPD, CAD and PUT and
      was applied to the determination of food samples ("budu", ketchup, orange juice,
      soy sauce) that were spiked with 20 mg L(-1) of the BAs. The extracted analytes
      were derivatized with dansyl chloride before the HPLC determination. With the
      exception of HIS and TYR in "budu" sample, reasonable recoveries were found for
      the other analytes in all the tested food samples.

PMID- 20801346
TI  - Sensitive coating for water vapors detection based on thermally sputtered calcein
      thin films.
AB  - In this paper the adsorption properties of thermally sputtered calcein thin films
      towards water and other polar molecules vapors are studied by different
      characterization techniques: quartz crystal microbalance, surface plasmon
      resonance and visible spectroscopy. Sensitivity of calcein thin films to water
      vapors resulted much higher as compared with those of a number of dyes whose
      structure was close to that of calcein. All types of sensors with calcein
      coatings have demonstrated linear concentration dependences in the wide range of
      water vapor pressure from low concentrations up to 27,000 ppm (close to
      saturation). At higher concentrations of water vapor all sensors demonstrate the
      abrupt increase of the response (up to two orders). A theoretical model is
      advanced explaining the adsorption properties of calcein thin films taking into
      account their chemical structure and peculiarities of molecular packing. The
      possibility of application of thermally sputtered calcein films in sensing
      technique is discussed.

PMID- 20801347
TI  - Comparison of fluorescence and QCM technologies: example of explosives detection
      with a pi-conjugated thin film.
AB  - A pi-conjugated compound was synthesized as a sensitive material for explosives
      detection. The detection of vapors of 2,4-dinitrotoluene was demonstrated with
      quartz crystal microbalance (QCM) and fluorescence transduction methods. The
      fluorescence intensity monitoring shows a higher sensitivity and selectivity than
      the monitoring of the QCM frequency. Both methods appear to be synergic when used
      simultaneously as the sensor helps to discriminate interferent vapors from
      nitroaromatics.

PMID- 20801348
TI  - Modeling the analytical response of optical fiber sensors for aromatic compounds
      determination.
AB  - In recent years, there has been an increasing interest in the application of
      optical fiber sensors for in situ monitoring of chemical pollutants, including
      volatile organic compounds, regarding air quality assurance. In order to enhance
      the usefulness and applicability of this methodology to environmental analysis, a
      proper study of the analytical signal and an adequate calibration model are
      required. This contribution is focused on the model for optical fiber sensors
      calibration, discussing some problems associated with the estimates of the
      figures of merit of these analytical systems. We also suggest and discuss a
      calibration model based on a cumulative symmetric double sigmoidal (SDS)
      function, as a suitable and general alternative to the more limited and classical
      linear calibration model.

PMID- 20801349
TI  - Decision peptide-driven: a free software tool for accurate protein quantification
      using gel electrophoresis and matrix assisted laser desorption ionization time of
      flight mass spectrometry.
AB  - The decision peptide-driven tool implements a software application for assisting
      the user in a protocol for accurate protein quantification based on the following
      steps: (1) protein separation through gel electrophoresis; (2) in-gel protein
      digestion; (3) direct and inverse (18)O-labeling and (4) matrix assisted laser
      desorption ionization time of flight mass spectrometry, MALDI analysis. The DPD
      software compares the MALDI results of the direct and inverse (18)O-labeling
      experiments and quickly identifies those peptides with paralleled loses in
      different sets of a typical proteomic workflow. Those peptides are used for
      subsequent accurate protein quantification. The interpretation of the MALDI data
      from direct and inverse labeling experiments is time-consuming requiring a
      significant amount of time to do all comparisons manually. The DPD software
      shortens and simplifies the searching of the peptides that must be used for
      quantification from a week to just some minutes. To do so, it takes as input
      several MALDI spectra and aids the researcher in an automatic mode (i) to compare
      data from direct and inverse (18)O-labeling experiments, calculating the
      corresponding ratios to determine those peptides with paralleled losses
      throughout different sets of experiments; and (ii) allow to use those peptides as
      internal standards for subsequent accurate protein quantification using (18)O
      labeling. In this work the DPD software is presented and explained with the
      quantification of protein carbonic anhydrase.

PMID- 20801350
TI  - The optimization of microwave digestion procedures and application to an
      evaluation of potentially toxic element contamination on a former industrial
      site.
AB  - The optimization of a microwave dissolution procedure for potentially toxic
      elements in a contaminated soil sample has been evaluated using a central
      composite design approach. By considering the operating parameters of
      temperature, digestion time, microwave power and acid volume it was possible to
      identify the following optimum conditions: temperature, 160 degrees C; power, 750
      W; digestion time, 25 min; and, an aqua regia volume of 13 mL. These microwave
      digestion conditions were then applied to 19 samples obtained from a former
      industrial site in Newcastle upon Tyne. Of the range of potentially toxic
      elements present at the site as a consequence of former industrial activity (As,
      Cd, Cr, Cu, Mo, Ni, Pb and Zn), the majority of topsoil samples indicated
      elevated concentrations of one or more of these elements. In particular, data
      obtained using either inductively coupled plasma mass spectrometry or flame
      atomic absorption spectroscopy indicates the high and wide concentration of Pb on
      the site (188-60300 mg/kg). Comparing the resulting potentially toxic elements
      data with UK soil guidelines values (SGVs) suggests at least parts of the site
      represent areas of potential human health risk. It was found that lead soil
      values exceeded the SGV on 17 out of the 19 sampling sites; similarly for As 6
      out of 19 sampling sites exceeded the SGV. While for Cd, Cr and Ni the soil
      levels were below the stated SGVs.

PMID- 20801351
TI  - Analyses of synthetic antioxidants by capillary electrochromatography using
      poly(styrene-divinylbenzene-lauryl methacrylate) monolith.
AB  - In this study, several organic polymer-based monoliths prepared by single step in
      situ copolymerization of styrene- and methacrylate ester-based monomers (styrene
      (S), divinylbenzene (DVB) and lauryl methacrylate (LMA)) were developed as
      stationary phases of capillary electrochromatography (CEC) for the analyses of
      synthetic antioxidants. These monoliths were characterized by examining the SEM
      image, IR spectrum, and measuring the pore size, surface area, conversion yield,
      and thermal decomposition temperature. The polymerization procedure was optimized
      by varying the reaction temperature, the reaction time, and the LMA-styrene
      ratio. The LMA-styrene ratio had the most significant influence on the peak
      symmetry of butylated hydroxyanisole (BHA) and 2, 6-di-tert-butyl-4-methyl phenol
      (BHT), the latter being greatly affected by excessive peak tailing in the poly(S
      DVB) monolith. It showed that the interaction between the poly(S-DVB) monolith
      and the antioxidant (BHT or BHA) was significantly altered by the insertion of
      LMA. Compared with the best HPLC and CE methods previously reported, this
      proposed CEC method provides a comparable separation ability for the five
      antioxidants analyzed. This study demonstrates that the potentiality of poly(S
      DVB-LMA) monolith as stationary phase, especially for CEC system, because of high
      thermal stability and good column reproducibility.

PMID- 20801353
TI  - Preparation, characterization, and analytical applications of a novel polymer
      stationary phase with embedded or grafted carbon fibers.
AB  - A polymer-based chromatographic stationary phase with embedded or grafted multi
      walled carbon nanotubes (MWCNTs) has been developed. Three different synthetic
      methods were utilized to combine the nano-fibers with the substrate of
      polystyrene-divinylbenzene (PS-DVB). After optimizing the synthetic conditions,
      this novel polystyrene-divinylbenzene-carbon nanotube (PS-DVB-CNT) stationary
      phase was characterized by scanning electron microscopy, Raman spectroscopy,
      thermogravimetric analysis, chemical adsorption and desorption measurement, and
      mechanical stability test. Compared to PS-DVB particles, PS-DVB-CNT particles
      have certain improvement in physical and chromatographic performances because the
      addition of MWCNTs has altered the structures of the particles. The novel
      stationary phase owns satisfactory resolution, wide pH endurance, and long
      lifetime, which can be used as an extent to normal HPLC.

PMID- 20801352
TI  - Fast quantification of the exhaled breath condensate of oxidative stress 8-iso
      prostaglandin F2alpha using on-line solid-phase extraction coupled with liquid
      chromatography/electrospray ionization mass spectrometry.
AB  - A method using automated on-line solid-phase extraction (SPE) liquid
      chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS) for the
      determination of 8-iso-PGF2alpha in human exhaled breath condensate (EBC) was
      developed and validated. A C18 SPE column with an affinity sorbent was used for
      on-line extraction. A C18 column was employed for LC separation and ESI-MS/MS was
      utilized for detection. 8-iso-PGF2alpha-d(4) was used as an internal standard for
      quantitative determination. The extraction, cleanup and analysis procedures were
      controlled by a fully automated six-port switch valve. Identification and
      quantification were based on the following transitions: m/z 353-->193 for 8-iso
      PGF2alpha and m/z 357-->197 for 8-iso-PGF2alpha-d(4), respectively. Good
      recoveries from 98.94 to 99.86% were measured and satisfactory linear ranges for
      these analytical compounds were determined. Intra-day and inter-day precision
      showed that coefficients of variance (CV) ranged from 6.5 to 8.0% and 5.2 to
      6.3%, respectively. The applicability of this newly developed method was
      demonstrated by analyzing human EBC samples for an evaluation of the future risk
      of human exposure to nanoparticles.

PMID- 20801354
TI  - Characterization of home-made silver sulphide based iodide selective electrode.
AB  - Polycrystalline silver sulphide/silver iodide ion selective electrodes (ISEs)
      with four different compositions, 9:1, 2:1, 1:1, 1:9 Ag(2)S-AgI mole ratios, have
      been fabricated in the laboratory and characterized by X-ray diffractometry
      (XRD), scanning electron microscopy (SEM), and electrochemical impedance
      spectroscopy (EIS). X-ray diffraction studies show the presence of Ag(3)SI,
      Ag(2)S and AgI crystalline phases in the electrode material. The electrode
      surfaces have been found to become smoother and lustrous with increasing
      percentage of silver sulphide in silver iodide. ISE 1:1, ISE 2:1 and ISE 9:1 all
      responded in Nernstian manner with slopes of about 60 mV/decade change in iodide
      ion concentration in the linear range of 1 x 10(-1) to 1 x 10(-6)M while ISE 1:9
      showed sub-Nernstian behavior with slope of about 45 mV up to the concentration 1
      x 10(-5)M. Two capacitive loops, one corresponding to the charge transfer process
      at metal electrode and the back contact and a second loop corresponding to the
      charge transfer process at membrane-electrolyte interface have been observed at
      high and low frequency ranges, respectively. Mott-Schottky analysis shows that
      the materials are n-type semiconductors with donor defect concentrations in the
      range of 5.1 x 10(14) to 2.4 x 10(19)/cm(3).

PMID- 20801355
TI  - Hot electron induced cathodic electrochemiluminescence at AuSb alloy electrode
      for fabricating immunosensor with self-assembled monolayers.
AB  - Thin antimony oxide covered AuSb alloy electrode was firstly found to be an
      excellent cold cathode for generating hot electrons during cathodic pulse
      polarization. Owing to the injection of hot electrons and the subsequent
      generation of hydrated electrons, fluorescein iso-thiocyanate (FITC) that cannot
      be excited in common ECL was cathodically excited at the alloy electrode. Self
      assembled thiol monolayers were formed on the electrode surface due to the
      presence of Au in the alloy, to which strepavidin was covalently bound, and then
      biotinylated antibody was immobilized through the strepavidin-biotin interaction.
      As a simple model, an immunosensor for the detection of human IgG (hIgG) using
      FITC as labeling agent was fabricated. ECL signals were responsive to the amount
      of hIgG bounded to the immunosensor. The ECL intensity was linearly changed with
      the logarithm of hIgG concentration in the range of 1.0-1000 ng mL(-1), and the
      detection limit was ca. 0.3 ng mL(-1) (S/N=3). The proposed immunosensor showed a
      broad linear range (three magnitudes), good reproducibility and stability, which
      is promising in detecting FITC-based labels in various types of bioaffinity
      assays.

PMID- 20801356
TI  - Automated chemiluminescent dual-analyte immunoassay based on resolved
      immunosensing channels.
AB  - A novel system of series-wound immunosensing channels (SWIC) was proposed for
      automated chemiluminescent (CL) dual-analyte immunoassay by immobilizing
      respectively different capture antibodies on the inner walls of series-wound
      glass channels. This system could use a single enzyme as label to perform
      multiplex immunoassay in one fluid way. Using alpha-fetoprotein (AFP) and
      carcinoembryonic antigen (CEA) as model analytes, the mixture including AFP,
      horseradish peroxidase (HRP)-labeled anti-AFP antibody, CEA and HRP-labeled anti
      CEA antibody was introduced into the SWIC for carrying out the on-line
      incubation. Upon injection of CL substrate the CL signals from the two
      immunosensing channels were conveniently resolved and near-simultaneously
      collected with the aid of optical shutter. AFP and CEA could be rapidly assayed
      in the ranges of 1.0-100 and 1.0-80 ng/ml with detection limits of 0.41 and 0.39
      ng/ml, respectively. The assay results of clinical serum samples were in an
      acceptable agreement with the reference values. This designed flow-through
      immunosensing system based on SWIC provided an automated, reusable, simple,
      sensitive and low-cost approach for multianalyte immunoassay.

PMID- 20801357
TI  - Sandwich-type electrochemiluminescence immunosensor based on Ru-silica@Au
      composite nanoparticles labeled anti-AFP.
AB  - A simple and sensitive sandwich-type electrochemiluminescence immunosensor for
      alpha-1-fetoprotein (AFP) on a gold nanoparticles (nano-Au) modified glassy
      carbon electrode (GCE) was developed by using Ru-silica (Ru(bpy)(3)(2+)-doped
      silica) doped Au (Ru-silica@Au) composite as labels. The primary antibody, anti
      AFP was first immobilized on the gold nanoparticles modified electrode due to the
      covalent conjugation, then the antigen and the Ru-silica@Au composite
      nanoparticles labeled secondary antibody was conjugated successively to form a
      sandwich-type immunocomplex through the specific interaction. The surfaces of Ru
      silica nanoparticles were modified via the assemble of Au nanoparticles. The
      prepared Ru-silica@Au composite nanoparticles own the large surface area, good
      biocompatibility and highly effective electrochemiluminescence properties. The
      morphologies of the Ru-silica@Au composite nanoparticles were investigated by
      using transmission electronic microscope (TEM). The Ru-silica@Au composite
      nanoparticles labeled anti-AFP/AFP/bovine serum albumin (BSA)/anti-AFP/nano-Au
      modified GCE electrode was evaluated by means of cyclic voltammetry (CV) and
      electrogenerated chemiluminescence (ECL). The immunosensor performed high
      sensitivity and wide liner for detection AFP in the range of 0.05-50 ng/mL and
      the limit detection was 0.03 ng/mL (defined as S/N=3).

PMID- 20801358
TI  - A secondary antibody format chemiluminescence immunoassay for the determination
      of estradiol in human serum.
AB  - A competitive immunoassay for estradiol (E2) based on secondary antibody format
      was established. The donkey anti-rabbit IgG was used as the secondary antibody to
      coat micro-plates, and the horseradish peroxidase (HRP)-luminol-H(2)O(2)
      chemiluminescent system with high sensitivity was chosen as the detection system.
      The addition of sodium trichloroacetate (CCl(3)COONa) in the enzyme buffer as a
      replaceable packing material can realize directly analysis of E2 in human serum
      without extraction, which improved reproducibility and resolution of the assay.
      Additionally, the method showed specific recognition of estrogen, without cross
      reaction for the major steroids (estrone (E1), estriol (E3), dihydrotestosterone
      (DHT), androstenedione, testosterone (T)) commonly found in human serum. The
      chemiluminescence immunoassay with secondary antibody can be applied to detect E2
      with good precision at concentrations as low as 1.48 pg mL(-1). The proposed
      method has been successfully applied to the determination of E2 in 97 human sera
      and showed a good correlation compared with the commercially radioimmunoassay
      (RIA) kit with a correlative coefficient of 0.9881. This method has exhibited
      great potential in the fabrication of diagnostic kit and can be used in the
      clinical analysis of E2 in human serum.

PMID- 20801359
TI  - Determination of trace metals in seawater by an automated flow injection ion
      chromatograph pretreatment system with ICPMS.
AB  - A novel flow injection ion chromatograph (FI-IC) system has been developed to
      fully automate pretreatment procedures for multi-elemental analysis of trace
      metals in seawater by inductively coupled plasma mass spectrometer (ICPMS). By
      combining 10-port, 2 position and 3-way valves in the FI-IC manifold, the system
      effectively increase sample throughput by simultaneously processing three
      seawater samples online for: sample loading, injection, buffering,
      preconcentration, matrix removal, metal elution, and sample collection. Forty-two
      seawater samples can be continuously processed without any manual handing. Each
      sample pretreatment takes about 10 min by consuming 25 mL of seawater and
      producing 5 mL of processed concentrated samples for multi-elemental offline
      analysis by ICPMS. The offline analysis improve analytical precision and
      significantly increase total numbers of isotopes determined by ICPMS, which
      include the metals Al, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Ti, V, and Zn. The blank
      value and detection limits of trace metals using the system with ICPMS analysis
      all range from 0.1 to 10 parts per trillion (ppt), except Al, Fe, and Zn. The
      accuracy of the pretreatment system was validated by measuring open-ocean and
      coastal reference seawater, NASS-5 and CASS-4. Using the system with ICPMS
      analysis, we have obtained reliable trace metal concentrations in the water
      columns of the South China Sea. Possessing the features of full automation, high
      throughput, low blank, and low reagent volume used, the system automates and
      simplifies rigorous and complicated pretreatment procedures for multi-elemental
      analysis of trace metals in seawater and effectively enhances analytical capacity
      for trace metal analysis in environmental and seawater samples.

PMID- 20801360
TI  - Room temperature ppb level Cl2 sensing using sulphonated copper phthalocyanine
      films.
AB  - We present room temperature chemiresistive gas sensing characteristics of drop
      casted sulphonated copper phthalocyanine (CuTsPc) films. It has been demonstrated
      that these films are highly selective to Cl(2) and the sensitivity in the 5-2000
      ppb range varies linearly between 65 and 625%. However, for concentrations
      >or=2000 ppb, the response becomes irreversible, which is found to be due to the
      chemical bond formation between Cl(2) and SO(3)Na group of CuTsPc films. The X
      ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) data
      confirms the oxidation of SO(3)Na group by Cl(2) gas.

PMID- 20801361
TI  - A HPLC method to evaluate the influence of photostabilizers on cosmetic
      formulations containing UV-filters and vitamins A and E.
AB  - This paper reports a simple and reliable HPLC method to evaluate the influence of
      two currently available photostabilizers on cosmetic formulations containing
      combined UV-filters and vitamins A and E. Vitamins and UV-filters, widely
      encountered in products of daily use have to be routinely evaluated since
      photoinstability can lead to reductions in their efficacy and safety. UV
      irradiated formulation samples were submitted to a procedure that included a
      reliable, precise and specific HPLC method employing a C18 column and detection
      at 325 and 235 nm. Methanol, isopropanol and water were the mobile phases in
      gradient elution. The method precision was between 0.28 and 5.07. The
      photostabilizers studied [diethylhexyl 2,6-naphthalate (DEHN) and benzotriazolyl
      dodecyl p-cresol (BTDC)], influenced the stability of octyl methoxycinnamate
      (OMC) associated with vitamins A and E. BTDC was considered the best
      photostabilizer to vitamins and OMC when the UV-filters were combined with both
      vitamins A and E.

PMID- 20801362
TI  - Development of a durable fiber-optic oxygen sensor for harsh underground
      environments.
AB  - This paper focuses on effects of protection with a silicone resin to develop a
      fiber-optic oxygen sensor with long-term stability and durability in harsh
      underground environments. Ruthenium (II) complexes were used as oxygen-sensing
      compounds. A uniform composite film composed of silicone resin and the Ru complex
      was prepared with spin coating technique. A comparison of dissolved-oxygen (DO)
      sensitivity between the composite film and a Ru complex film was made by exposing
      to hot water (80 degrees C). The result of the accelerated degradation test
      showed that sensitivity of the Ru complex film was stable; meanwhile that of the
      composite film increased with exposure time in a short period. In order to
      improve stability, the Ru complex film overcoated with silicone resin was
      prepared. Differences in sensitivity for saturated DO (8.5 ppm) between with and
      without the silicone resin overcoating on the Ru complex film were investigated
      by exposing to the hot water and simulated underground water. These results
      revealed that the sensitivities and response times of the overcoated films were
      stable and slow, respectively, compared to those of non-overcoated films. Then,
      optodes were evaluated for effects of the overcoating on sensing properties by
      exposing to 100 vol.% oxygen gas. The experiment showed that: (1) the response
      time was significantly influenced by the thickness of the overcoating; and (2)
      response speed of the overcoated optode was slow by a factor of about 35 compared
      to that of the non-overcoated. We concluded that the overcoating was effective in
      the application to mid- and long-term oxygen monitoring in the harsh
      environments.

PMID- 20801363
TI  - Lab-on-valve (LOV) system coupled to irreversible biamperometric detection for
      the on-line monitoring of catechol.
AB  - The analytical performance of lab-on-valve (LOV) system using irreversible
      biamperometry for the determination of catechol was evaluated. By integrating
      miniaturized electrochemical flow cell (EFC) designed and processed which is
      furnished with two identical polarized platinum electrodes, into the LOV unit,
      the lab-on-valve system combines sampling with analysis, realizing automated on
      line analysis for catechol in a closed system. The biamperometric detection
      system was established to record the relationship between oxidation current and
      time by coupling the irreversible oxidation of catechol at one pretreated
      platinum electrode with the irreversible reduction of platinum oxide at the other
      pretreated platinum electrode. Factors influencing the analytical performance
      were optimized, including the potential difference (DeltaE), buffer solution and
      pH, and flow variables in the LOV. A linear calibration curve was obtained within
      the range of 1.0 x 10(-6)-5.0 x 10(-4) mol L(-1) of catechol with the detection
      limit (3 sigma) of 5.09 x 10(-7)mol L(-1). The relative standard deviation
      (R.S.D.) was 2.39% for 11 successive determinations of 1 x 10(-5)mol L(-1)
      catechol and the sample throughput was 35h(-1). Moreover, this proposed method
      was applied to the analysis of catechol in beer sample, which was testified by
      high-performance liquid chromatography (HPLC).

PMID- 20801364
TI  - Non-chromatographic screening method for the determination of mercury species.
      Application to the monitoring of mercury levels in Antarctic samples.
AB  - A simple non-chromatographic method for the determination of mercury (Hg(2+)),
      methylmercury (MeHg(+)), dimethylmercury (Me(2)Hg), and phenylmercury (PhHg(+))
      employing atomic fluorescence spectrometry (AFS) as detection technique was
      developed. Mercury species showed a particular behavior in the presence of
      several reagents. In a first stage SnCl(2) was employed for Hg(2+) determination;
      in a second step, [Hg(2+)+PhHg(+)] concentration was determined using SnCl(2) and
      UV radiation. MeHg(+) decomposition was prevented adding 2-mercaptoethanol. In a
      third stage, [Hg(2+)+PhHg(+)+MeHg(+)] concentration was determined using
      K(2)S(2)O(8). Finally, the four species were determined employing NaBH(4).
      Reagents concentration and flow rates were optimized. The extraction technique of
      mercury species involved the use of 2-mercaptoethanol as ion-pair reagent. The
      limits of detection for Hg(2+), PhHg(+), MeHg(+), and Me(2)Hg were 1, 40, 68, and
      99 ng L(-1) with a relative standard deviation of 1.5, 3.1, 4.7 and 5.8%,
      respectively. Calibration curve was linear with a correlation factor equal to
      0.9995. The method was successfully applied to the determination of the mercury
      species in two Antarctic materials: IRMM 813 (Adamussium colbecki) and MURST-ISS
      A2 (Antarctic Krill).

PMID- 20801365
TI  - A highly soluble poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonic acid)/Au
      nanocomposite for horseradish peroxidase immobilization and biosensing.
AB  - A highly soluble poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonic acid)/Au
      (PEDOT-PSS/Au) nanocomposite was prepared via one-step chemical synthesis and the
      matrix was characterized by UV-vis spectroscopy (UV-vis), Fourier transform
      infrared spectroscopy (FT-IR), scanning electron microscope (SEM) and
      transmission electron microscope (TEM). Due to the excellent aqueous
      compatibility and biocompatibility, the PEDOT/PSS-Au nanocomposite can be used as
      biomaterial for enzymes immobilization. In this system, redox enzyme, horseradish
      peroxidase (HRP) was integrated with PEDOT/PSS-Au nanocomposite and the direct
      electron transfer of HRP was observed. Moreover, we find that the HRP/PEDOT
      PSS/Au modified electrode shows excellent electrocatalytic ability for H(2)O(2)
      and the formal Michaelis-Menten constant (K(m)(app)) was 0.78 mmol/L. The
      response currents have good linear relation with the concentrations of H(2)O(2)
      with a linear range from 2.0 x 10(-7) to 3.8 x 10(-4)mol/L.

PMID- 20801366
TI  - Rapid simultaneous determination of protoporphyrin IX, uroporphyrin III and
      coproporphyrin III in human whole blood by non-linear variable-angle synchronous
      fluorescence technique coupled with partial least squares.
AB  - Fluorescence spectroscopy provides high sensitivity in quantitative analysis.
      However, due to spectral interference, it is difficult to determine the
      individual components of fluorescent multi-component mixtures in such complicated
      and important body matrices as blood, urine and feces without any pre-separation.
      In this study, a simple and rapid approach based on non-linear variable-angle
      synchronous fluorescence spectrometry coupled with partial least squares analysis
      (NLVASF/PLS) was developed for the simultaneous determination of protoporphyrin
      IX (PP), uroporphyrin III (UP) and coproporphyrin III (CP). The detection limits
      were 0.18, 0.29 and 0.24 nmol L(-1) for protoporphyrin IX (PP), uroporphyrin III
      (UP) and coproporphyrin III (CP), respectively. The individual components of
      blood porphyrins were quantified, by this method, simultaneously in one scan with
      only about 30s. The recoveries of this method were above 80% in human whole blood
      samples. This method provided a potential tool for the determination of
      porphyrins in whole blood and the differential diagnosis of porphyria, especially
      for rapid routine screening of large number of samples.

PMID- 20801367
TI  - Quick identification of apoptosis inducer from Isodon eriocalyx by a drug
      discovery platform composed of analytical high-speed counter-current
      chromatography and the fluorescence-based caspase-3 biosensor detection.
AB  - Analytical high-speed counter-current chromatography (HSCCC), a unique liquid-to
      liquid separation technology, has an inherent capability to provide perfect
      fractionation for tracking active ingredients of medicinal herbs, in a quick,
      efficient, and high-recovery manner. A high throughput screening (HTS) method
      which utilizes a novel biosensor that selectively detects apoptosis based on the
      fluorescence resonance energy transfer (FRET) technique, was newly established
      and proved to be very sensitive in detecting apoptosis induced by various known
      anticancer drugs. The first combination of both advanced techniques formed an
      efficient platform for drug discovery and succeeded in quickly identifying the
      most potent apoptotic constituent of a Chinese herb namely Isodon eriocalyx. The
      system of n-hexane/ethyl acetate/methanol/water was used as the separation
      solvent. The solvent ratio was first set at 3:5:3:5 to check the water-soluble
      part of the crude extract, and then 1:1:1:1 was used to isolate the target
      compounds. The active fraction was tracked and purified continuously using HSCCC
      which was guided by the apoptosis detection at gradually decreased drug
      concentrations. As a result, the most potent apoptosis inducer in this herb was
      discovered by analytical HSCCC equipped with a 16 ml mini-coil column, using less
      than 50 ml diphase solvent, from about 50mg active fraction. It was identified as
      eriocalyxin B, a well-known antitumor natural product, by NMR analysis of the
      HSCCC purified fraction.

PMID- 20801368
TI  - Determination of pK(a) values of some antihypertensive drugs by liquid
      chromatography and simultaneous assay of lercanidipine and enalapril in their
      binary mixtures.
AB  - In this study, pK(a) values were determined using the dependence of the retention
      factor on the pH of the mobile phase for three ionizable substances, namely,
      enalapril, lercanidipine and ramipril (IS). The effect of the mobile phase
      composition on the ionization constant was studied by measuring the pK(a) at
      different methanol-water mixtures, ranging between 50 and 65% (v/v), using LC-DAD
      method. Two simple, accurate, precise and fully validated analytical methods for
      the simultaneous determination of enalapril and lercanidipine in combined dosage
      forms have been developed. Separation was performed on an X-Terra RP-18 column
      (250 mm x 4.60mm ID x 5 microm) at 40 degrees C with the mobile phase of methanol
      water 55:45 (v/v) adjusted to pH 2.7 with 15 mM orthophosphoric acid. Isocratic
      elution was performed in less than 12 min with a flow rate of 1.2 mL min(-1).
      Good sensitivity for the analytes was observed with DAD detection. The LC method
      allowed quantitation over the 0.50-20.00 microg mL(-1) range for enalapril and
      lercanidipine. The second method depends on first derivative of the ratio-spectra
      by measurements of the amplitudes at 219.7 nm for enalapril and 233.0 nm for
      lercanidipine. Calibration graphs were established for 1-20 microg mL(-1) for
      enalapril and 1-16 microg mL(-1) lercanidipine, using first derivative of the
      ratio spectrophotometric method. Both methods have been extensively validated.
      These methods allow a number of cost and time saving benefits. The described
      methods can be readily utilized for analysis of pharmaceutical formulations. The
      methods have been applied, without any interference from excipients, for the
      simultaneous determination of these compounds in tablets. There was no
      significant difference between the performance of the proposed methods regarding
      the mean values and standard deviations.

PMID- 20801369
TI  - A novel benzothiazole based azocalix[4]arene as a highly selective chromogenic
      chemosensor for Hg2+ ion: a rapid test application in aqueous environment.
AB  - A novel calix[4]arene derivative containing benzothiazole azo groups at the upper
      rim was synthesized as chromogenic chemosensor, and its binding and sensing
      properties with heavy metal ions (Pb(2+), Hg(2+), Ni(2+), Cd(2+), Cu(2+), Zn(2+),
      Co(2+), Fe(2+), Mn(2+), Cr(3+), Ag(+)) were investigated by UV-vis spectroscopy
      and voltammetric techniques. The results of spectroscopic and voltammetric
      experiments showed that the chromogenic chemosensor has high selectivity towards
      Hg(2+) ion over the other heavy metal ions. Moreover, it was shown that the
      interaction between Hg(2+) and the chromogenic chemosensor occurs by means of the
      benzothiazole azo groups at the upper rim by using differential pulse
      voltammetry. The stoichiometric ratio and the association constant were
      determined as 1:1 and (6.1+/-0.3)x10(5) L mol(-1) for the complex between Hg(2+)
      and the ionophore. Furthermore, we prepared a rapid test kit for early detection
      of Hg(2+) in aqueous environment in the concentration range of 1 x 10(-4) to 1 x
      10(-2)M.

PMID- 20801370
TI  - Monitoring of melamine contamination in fat watery milk by the photoluminescence
      analysis.
AB  - A photoluminescence method to detect the toxic melamine contamination in fat
      watery milk has been proposed. Despite the quite different luminescence origins
      of milk and melamine patterns, their wide emission spectra under UV excitation
      are similar and in the range of 2.2-3.5 eV. The complex milk photoluminescence
      spectrum composed of riboflavin, furosine, lactulose, Vitamin E and tryptophan
      emitting species can be modified if milk pattern is undergone by acid treatment
      (for example, in vinegar). At the same time the melamine emission is not
      subjected to any modification in vinegar. It allows quantitatively discriminating
      the melamine contamination in milk in linear range, at least, 0.05-7 g/l from
      different photoluminescence spectra of milk (water) with and without melamine.
      Limit of melamine detection achieves 0.01 g/l.

PMID- 20801371
TI  - Improved sample treatment for the determination of insoluble soap in sewage
      sludge samples by liquid chromatography with fluorescence detection.
AB  - A new selective and sensitive method for the determination of insoluble fatty
      acid salts (soap) in sewage sludge samples is proposed. The method involves a
      clean up of sample with petroleum ether, the conversion of calcium and magnesium
      insoluble salts into soluble potassium salts, potassium salts extraction with
      methanol, and a derivatization procedure previous to the liquid chromatography
      with fluorescence detection (LC-FLD) analysis. Three different extraction
      techniques (Soxhlet, microwave-assisted extraction and ultrasounds) were compared
      and microwave-assisted extraction (MAE) was selected as appropriate for our
      purpose. This allowed to reduce the extraction time and solvent waste (50 mL of
      methanol in contrast with 250 mL for Soxhlet procedure). The absence of matrix
      effect was demonstrated with two standards (C(13:0) and C(17:0)) that are not
      commercials and neither of them has been detected in sewage sludge samples.
      Therefore, it was possible to evaluate the matrix effect since both standards
      have similar environmental behaviour (adsorption and precipitation) to commercial
      soaps (C(10:0)-C(18:0)). The method was successfully applied to samples from
      different sources and consequently, with different composition.

PMID- 20801372
TI  - Ochratoxin A survey in Portuguese wine by LC-FD with direct injection.
AB  - Wine and grape juices were identified as one of the most important sources of
      ochratoxin A (OTA), a mycotoxin with diverse toxic effects that naturally appears
      in food and foodstuffs all over the world. The aim of this study was to assess
      the OTA levels in Portuguese wines through the application of a simple and
      accurate method based on liquid chromatography (LC) with direct injection,
      followed by fluorescence detection (FD). Randomly selected wine samples were used
      to evaluate the performance of direct injection as efficient, fast, inexpensive
      and safe sample preparation method. The proposed method was successfully
      validated. The limit of quantification (LOQ) was 1.0 microg/L and OTA recoveries
      from wine samples, spiked at the three fortification levels, were higher than
      85.4%, with RSDs lower than 9.6% for both red and white wines. The presence of
      OTA was confirmed by methyl ester derivatization followed by LC analysis. Data on
      OTA levels were obtained for 60 Portuguese red and white wine samples. OTA was
      found in 12 samples, nine (26%) red wine samples and three (12%) white wine
      samples. Only one red wine sample and one white wine sample presented a
      contamination level above the LOQ, with 1.23 and 2.4 microg/L, respectively. It
      should be pointed out that this white wine sample exceeded the EC maximum
      permitted level of 2.0 microg/L. The safe dose established as 120 ng/kg body
      weight/week was not exceeded by the weekly intake estimated for the samples
      contaminated above the LOQ.

PMID- 20801373
TI  - Multiresidue determination of (fluoro)quinolone antibiotics in chicken by polymer
      monolith microextraction and field-amplified sample stacking procedures coupled
      to CE-UV.
AB  - Simultaneous determination of 9 (fluoro)quinolone antibiotics (FQs) was
      accomplished by capillary electrophoresis-ultraviolet (CE-UV) based on
      poly(methacrylic acid-co-ethylene glycol dimethacrylate) (MAA-EGDMA) monolith
      microextraction (PMME) coupled with on-line preconcentration technique of field
      amplified sample stacking (FASS). The effects of composition of the acid and
      organic solvent in the sample solution, sampling time, and voltage on the
      efficiency of the sample stacking have been systematically investigated. Several
      parameters that influence extraction efficiency for PMME such as pH of sample
      solution, extraction volume, and wash and desorption conditions were optimized.
      In the proposed method, a substantial increase in sensitivity for all the FQs
      tested was achieved by the combination of PMME procedure with on-line
      preconcentration of FASS prior to CE analysis. Good linearities were obtained for
      the 9 tested FQs with the correlation coefficients (R) above 0.9954. The limits
      of detection (S/N=3) were found to be 2.4-34.0 ng g(-1) and the recoveries ranged
      from 81.2 to 100% with relative standard deviations less than 11.3%. The proposed
      PMME-FASS-CE method was applied to the determination of FQs residues in chicken
      samples.

PMID- 20801375
TI  - Determination of bisphenol A based on chemiluminescence from gold(III)
      peroxymonocarbonate.
AB  - Peroxymonocarbonate (HCO(4)(-)) was produced by the online reaction of
      bicarbonate with hydrogen peroxide. A strong chemiluminescence (CL) was observed
      when HCO(4)(-) reacted with AuCl(4)(-) without any special CL reagent. When
      bisphenol A (BPA) was added to AuCl(4)(-)-HCO(4)(-) CL system, the CL emission
      was inhibited significantly. This new CL system was developed as a flow-injection
      method for the determination of BPA. Under the optimum experimental conditions,
      the inhibited CL intensity was linearly related to the concentration of BPA from
      0.3 to 80 microM (R=0.9958). The detection limit of BPA was 0.08 microM. The
      relative standard deviation for 12 repeated measurements of 1.0 microM BPA was
      2.9%. The interferences of some cationic ions can be removed by an online cation
      exchange column. The applicability of the present CL system was demonstrated for
      the sensitive and selective determination of BPA in real samples (mineral water
      bottle, baby bottle, beverage bottle and polycarbonate container). Based on the
      CL spectrum, UV-visible adsorption spectra, and the quenching effect of reactive
      oxygen species scavengers, a possible CL mechanism was proposed.

PMID- 20801374
TI  - A random forest of combined features in the classification of cut tobacco based
      on gas chromatography fingerprinting.
AB  - We applied the random forest method to discriminate among different kinds of cut
      tobacco. To overcome the influence of the descending resolution caused by column
      pollution and the subsequent deterioration of column efficacy at different
      testing times, we constructed combined peaks by summing the peaks over a specific
      elution time interval Deltat. On constructing tree classifiers, both the original
      peaks and the combined peaks were considered. A data set of 75 samples from three
      grades of the same tobacco brand was used to evaluate our method. Two parameters
      of the random forest were optimized using out-of-bag error, and the relationship
      between Deltat and classification rate was investigated. Experiments show that
      partial least squares discriminant analysis was not suitable because of the
      overfitting, and the random forest with the combined features performed more
      accurately than Naive Bayes, support vector machines, bootstrap aggregating and
      the random forest using only its original features.

PMID- 20801376
TI  - Enzyme-linked immunosorbent assays for the synthetic steroid gestrinone.
AB  - Gestrinone is a synthetic steroid hormone with anti-estrogenic and anti
      progesterone properties. It is used to treat endometriosis, shrink uterine
      fibroids and reduce menorrhagia; besides, it has been investigated for use as
      contraceptive. Also, due to its anabolic effects, it has been included in the
      banned list of performance enhanced drugs in sport. Polyclonal antibodies raised
      against bovine serum albumin coupled to gestrinone 3-carboxymethyloxime (3OCMO-G)
      were used to develop two highly sensitive and specific enzyme-linked
      immunosorbent assays for gestrinone. One of them, based on direct format, shows a
      detection limit (LD) of 0.09+/-0.03 ng L(-1). The second assay, hapten-protein
      coating format, can detect until (LD) 0.14+/-0.05 ng L(-1). Both immunoassays
      were also highly specific, showing negligible or no cross-reactivity to other
      anabolic steroids. The developed ELISAs detected lower amounts of gestrinone than
      those determined by the reference chromatographic HPLC/MS/MS methods. The direct
      format was applied to quantify this steroid in spiked human urine without sample
      pre-treatment, with recovery values between 76 and 122%.

PMID- 20801377
TI  - Combined hollow fiber-based liquid-liquid-liquid microextraction and in-situ
      differential pulse voltammetry to improve selectivity, sensitivity, and
      interference elimination in electrochemical analysis.
AB  - In this paper, a combined hollow fiber-based liquid three-phase microextraction
      and voltammetric method are applied for the first time as a highly selective and
      sensitive method of electrochemical analysis. Desipramine, used as a model
      compound was extracted from 8 mL aqueous solution (donor phase, 0.10 mol L(-1)
      NaOH) through a thin phase of propyl benzoate inside the pores of a polypropylene
      hollow fiber and finally into a 10 microL acidic acceptor solution inside the
      hollow fiber. Three microelectrodes designed and constructed for the purposes of
      this study were placed into the two ends of the hollow fiber inside the acceptor
      solution, and voltammetric analysis was performed in-situ during the extraction.
      After 15 min, the final stable signal was used for analytical applications. Under
      the optimized conditions, an enrichment factor of 301 was achieved and the
      relative standard deviation (R.S.D.) of the method was 6.2% (n=5). The
      calibration curve was obtained in the range of 5-5000 nmol L(-1) with a
      reasonable linearity (R(2)>0.988) and the limit of detection (LOD) was found to
      be 0.8 nmol L(-1). Finally, the applicability of the proposed method was
      evaluated by extraction and determination of desipramine in plasma and urine
      samples without any dilutions.

PMID- 20801378
TI  - A robust new strategy for high-molecular-weight proteome research: a 2
      hydroxyethyl agarose/polyacrylamide gel enhanced separation and ZnO-PMMA
      nanobeads assisted identification.
AB  - A new mass spectrometry based analysis strategy has been established here for
      high-molecular-weight (HMW) proteome research. First, a 2-hydroxyethyl
      agarose/polyacrylamide (HEAG/PAM) electrophoresis gel was designed for the first
      time to realize an easy-handling separation method with high spatial resolution
      for HMW proteins, good reproducibility and mass spectrometry-compatible silver
      staining. Second, ZnO-polymethyl methacrylate (ZnO-PMMA) nanobeads were applied
      here for enriching and desalting the peptides from the HMW proteins. Third, the
      peptides were analyzed by matrix-assisted laser desorption/ionization-mass
      spectrometry (MALDI-MS) with the presence of the ZnO-PMMA nanobeads, and their MS
      signals were enhanced markedly. The success rate of identification for HMW
      proteins was significantly increased due to high enriching efficiency and salt
      tolerance capability as well as signal enhancing capability of the ZnO-PMMA
      nanobeads. We believe that this analysis strategy will inspire and accelerate the
      HMW proteome studies.

PMID- 20801379
TI  - Direct amperometric determination of tert-butylhydroquinone in biodiesel.
AB  - The direct amperometric determination of tert-butylhydroquinone (TBHQ) in
      biodiesel at an unmodified glassy carbon electrode is reported. A biodiesel
      aliquot was added into an electrochemical cell containing a 75% (v/v) ethanol
      water solution under stirring (with final concentration of 50 mmol L(-1)
      HClO(4)). The amperometric method involved the continuous application of three
      sequential potential pulses to the working electrode (700 mV for 300 ms, 0 mV for
      100 ms and -50 mV for 1s). TBHQ was continuously monitored at the first (direct
      oxidation) and optionally at the second (reduction) potential pulse while the
      third potential pulse was applied for cleaning of the electrode surface. For
      comparison, the samples were also analyzed by high-performance liquid
      chromatography and a good agreement between the results was verified. Recovery
      values for spiked samples were between 90% and 95% and the reproducibility of the
      proposed method was around 5% (n=5). The proposed method can be easily adapted
      for on-site analysis.

PMID- 20801380
TI  - Simultaneous determination of diclofenac potassium and methocarbamol in ternary
      mixture with guaifenesin by reversed phase liquid chromatography.
AB  - New, simple, rapid and precise reversed phase liquid chromatographic (RP-LC)
      method has been developed for the simultaneous determination of diclofenac
      potassium (DP) and methocarbamol (MT) in ternary mixture with guaifenesin (GF),
      degradation product of methocarbamol. Chromatographic separation was achieved on
      a Symmetry Waters C18 column (150 mm x 4. 6mm, 5 microm). Gradient elution based
      on phosphate buffer pH (8)-acetonitrile at a flow rate of 1 mL min(-1) was
      applied. The UV detector was operated at 282 nm for DP and 274 nm for MT and GF.
      Linearity, accuracy and precision were found to be acceptable over the
      concentration ranges of 0.05-16, 0.5-160 and 0.5-160 microg mL(-1) for DP, MT and
      GF, respectively. The optimized method proved to be specific, robust and accurate
      for the quality control of the cited drugs in pharmaceutical preparation.

PMID- 20801381
TI  - Selective and specific detection of sulfate-reducing bacteria using
      potentiometric stripping analysis.
AB  - A fast, sensitive and reliable potentiometric stripping analysis (PSA) is
      described for the selective detection of the marine pathogenic sulfate-reducing
      bacterium (SRB), Desulforibrio caledoiensis. The chemical and electrochemical
      parameters that exert influence on the deposition and stripping of lead ion, such
      as deposition potential, deposition time and pH value were carefully studied. The
      concentration of SRB was determined in acetate buffer solution (pH 5.2) under the
      optimized condition (deposition potential of -1.3V, deposition time of 250s,
      ionic strength of 0.2 mol L(-1) and oxidant mercury (II) concentration of 40 mg
      L(-1)). A linear relationship between the stripping response and the logarithm of
      the bacterial concentration was observed in the range of 2.3 x 10 to 2.3 x 10(7)
      cfu mL(-1). In addition, the potentiometric stripping technique gave a distinct
      response to the SRB, but had no obvious response to Escherichia coli. The
      measurement system has a potential for further applications and provides a facile
      and sample method for detection of pathogenic bacteria.

PMID- 20801382
TI  - Rapid simultaneous determination of nitrate and nitrite on a centrifugal
      microfluidic device.
AB  - A centrifugal microfluidic device was developed for the rapid sequential
      determination of two critical environmental species, nitrate and nitrite, in
      water samples. The nitrate is reduced to nitrite and the nitrite is derivatized.
      The analytes are determined spectrophotometrically through the disc with a 1.4mm
      pathlength. The detection limits are 0.05 and 0.16 mg L(-1) for nitrite and
      nitrate respectively. The use of powdered reagents, the 100 microL sample
      required and the design of the device suggest that it would be suitable for field
      use.

PMID- 20801383
TI  - Molecular fluorescence analysis of rainwater: effects of sample preservation.
AB  - Very different filtration and preservation procedures may be found in the
      literature on the study of the rainwater dissolved organic fraction. Thus, the
      influence of sample filtration and preservation procedures on the fluorescence of
      rainwater dissolved organic matter (DOM) was studied in this work. Rainwater was
      filtered through different filters (quartz 0.22 microm or PVDF 0.45 microm) and
      excitation (lambda(em)=415 nm) and synchronous (Deltalambda=70 nm) fluorescence
      spectra were obtained at the same day of collection, or after preservation by
      refrigeration (1-7 days) or by freezing (1-4 weeks). The excitation-emission
      matrix (EEM) spectra of rainwater showed six types of fluorescent bands: two
      corresponding to humic-like bands, and four resembling proteins. Then, the
      excitation and synchronous spectra were chosen in order to monitor changes in the
      humic-like and protein-like bands, respectively. The filtration procedures
      adopted in this work did not affect the fluorescence properties of the rainwater
      samples. However, these properties were differently preserved by refrigeration or
      freezing: after refrigeration, filtered rainwater maintained the original
      fluorescent properties for at least 4 days, while after freezing fluorescent
      properties were not always preserved since it occurred a decrease of protein-like
      fluorescence intensity.

PMID- 20801384
TI  - TritonX-100 selective chemosensor based on beta-cyclodextrin modified by
      anthracene derivative.
AB  - Beta-cyclodextrin (CD) modified by 2-(9-anthracenecarboxamido)phenyl group (Ant
      CD) was synthesized and their complexation behavior was investigated by UV and
      fluorescence spectroscopy. Fluorescence intensity of Ant-CD was dramatically
      enhanced ca. 10-fold by the addition of TritonX-100 (TX-100) in water below the
      critical micelle concentration. Ant-CD also showed ca. 4-fold fluorescence
      increasing in the addition of analogous materials, n-octylbenzenesulfonate in
      water. These results indicate that Ant-CD can act as a highly sensitive and
      selective chemosensor for TX-100. Ant-CD and TX-100 formed a pseudorotaxane
      supramolecular complex. This result was supported by (1)H-(1)H NOESY NMR
      measurement.

PMID- 20801385
TI  - Chinese doctors are under threat.

PMID- 20801386
TI  - What makes a good doctor?

PMID- 20801387
TI  - Why are drug trials in Alzheimer's disease failing?

PMID- 20801388
TI  - The unfolding human tragedy in Pakistan: fighting alone.

PMID- 20801389
TI  - The James Lind Alliance: tackling research mismatches.

PMID- 20801390
TI  - The potato: fertile ground for more funding.

PMID- 20801392
TI  - Bernard Pecoul: championing the cause of neglected diseases.

PMID- 20801394
TI  - Extensively drug-resistant tuberculosis in South Africa.

PMID- 20801395
TI  - Extensively drug-resistant tuberculosis in South Africa.

PMID- 20801396
TI  - Multidrug-resistant tuberculosis in India.

PMID- 20801397
TI  - Opportunistic screening for type 2 diabetes in primary care.

PMID- 20801398
TI  - Where is diabetes in The Lancet's tuberculosis Series?

PMID- 20801400
TI  - Like-with-like comparisons?

PMID- 20801401
TI  - Preventable cancer in the USA.

PMID- 20801402
TI  - Changing doctors in changing times.

PMID- 20801403
TI  - Galen's "errors".

PMID- 20801404
TI  - Endometriosis and infertility: pathophysiology and management.
AB  - Endometriosis and infertility are associated clinically. Medical and surgical
      treatments for endometriosis have different effects on a woman's chances of
      conception, either spontaneously or via assisted reproductive technologies (ART).
      Medical treatments for endometriosis are contraceptive. Data, mostly
      uncontrolled, indicate that surgery at any stage of endometriosis enhances the
      chances of natural conception. Criteria for non-removal of endometriomas are:
      bilateral cysts, history of past surgery, and altered ovarian reserve. Fears that
      surgery can alter ovarian function that is already compromised sparked a rule of
      no surgery before ART. Exceptions to this guidance are pain, hydrosalpinges, and
      very large endometriomas. Medical treatment-eg, 3-6 months of gonadotropin
      releasing hormone analogues-improves the outcome of ART. When age, ovarian
      reserve, and male and tubal status permit, surgery should be considered
      immediately so that time is dedicated to attempts to conceive naturally. In other
      cases, the preference is for administration of gonadotropin-releasing hormone
      analogues before ART, and no surgery beforehand. The strategy of early surgery,
      however, seems counterintuitive because of beliefs that milder non-surgical
      options should be offered first and surgery last (only if initial treatment
      attempts fail). Weighing up the relative advantages of surgery, medical treatment
      and ART are the foundations for a global approach to infertility associated with
      endometriosis.

PMID- 20801405
TI  - A harmless high?

PMID- 20801407
TI  - Advances and challenges in translating stem cell therapies for clinical diseases.

PMID- 20801408
TI  - Bone marrow and circulating stem/progenitor cells for regenerative cardiovascular
      therapy.
AB  - Cardiovascular disease is the leading cause of death and disability in the
      Western world. In addition to the advancement of current therapeutic approaches
      to reduce the associated morbidity and mortality, regenerative medicine and cell
      based therapy have been areas of continuous investigation. Circulating and bone
      marrow-derived stem or endothelial progenitor cells are an attractive source for
      regenerative therapy in the cardiovascular field. In this review, we highlight
      the advantages and limitations of this approach with a focus on key observations
      from animal studies and clinical trials.

PMID- 20801409
TI  - New therapies for the failing heart: trans-genes versus trans-cells.
AB  - During the past 30 years, hundreds of pharmacological agents have been developed
      for the treatment of heart failure; yet few of them ultimately have been tested
      in patients. Such a disconcerting debacle has spurred the search for non
      pharmacological therapies, including those based on cardiac delivery of
      transgenes and stem cells. Cardiac gene therapy preceded stem cell therapy by
      approximately 10 years; however, both of them already have known an initial phase
      of enormous enthusiasm followed by moderate-to-strong skepticism, not necessarily
      justified. The aim of the present review is to discuss succinctly some key
      aspects of these 2 biological therapies and to argue that, after a phase of
      disillusionment, gene therapy for the failing heart likely will have the chance
      to regain the stage. In fact, discoveries in stem cell biology might revitalize
      gene therapy and, vice versa, gene therapy might potentiate synergistically the
      regenerative capacity of stem cells.

PMID- 20801410
TI  - Endothelial lineage cell as a vehicle for systemic delivery of cancer gene
      therapy.
AB  - A major limitation of cancer gene therapy is the difficulty of delivering a
      therapeutic gene to distant sites of metastatic disease. A promising strategy to
      address this difficulty is to use expanded ex vivo cells to produce a therapeutic
      protein. As with other approaches to gene therapy, this strategy is attractive
      when the therapeutic protein is unstable ex vivo or has a short circulating half
      life in vivo. The initial step to develop a cancer gene therapy using autologous
      cell delivery is the identification of a cell type that migrates to the tumor
      site, is readily available for harvesting, and is manipulated easily ex vivo.
      Recent evidence suggests that endothelial progenitor, precursor, and blood
      outgrowth endothelial cells are attracted to the tumor vasculature by its
      angiogenic drive. Here, we review recent advances in the study of circulating
      endothelial cell-mediated tumor vasculogenesis and discuss the advantages and
      challenges of bringing endothelial lineage-based cancer gene therapy closer to
      clinical application.

PMID- 20801412
TI  - Translation of stem cell therapy for neurological diseases.
AB  - "Regenerative medicine" hopefully will provide novel therapies for diseases that
      remain without effective therapy. This development is also true for most
      neurodegenerative disorders including Alzheimer's disease, Huntington's disease,
      or Parkinson's disease. Transplantation of new neurons to the brain has been
      performed in Parkinson's disease and in Huntington's disease. The restoration of
      dopaminergic neurons in patients with Parkinson's disease via implantation of
      embryonic midbrain tissue was taken from animal experiments to clinical
      applications, showing a limited efficacy. Clinical trials in patients with
      Huntington's disease using fetal striatal tissue currently are underway. Today,
      it seems possible to generate functional dopaminergic or striatal neurons form a
      variety of stem cells including embryonic or neural stem cells as well as induced
      pluripotent stem cells. First clinical trials using neural stem cell or embryonic
      stem-cell-derived tissue are approved or already underway. Such cells allow for
      extensive in vitro and in vivo testing as well as "good manufacturing
      production," reducing the risks in clinical application.

PMID- 20801411
TI  - Pluripotent stem cell-derived natural killer cells for cancer therapy.
AB  - Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs)
      provide an accessible, genetically tractable, and homogenous starting cell
      population to efficiently study human blood cell development. These cell
      populations provide platforms to develop new cell-based therapies to treat both
      malignant and nonmalignant hematological diseases. Our group previously
      demonstrated the ability of hESC-derived hematopoietic precursors to produce
      functional natural killer (NK) cells as well as an explanation of the underlying
      mechanism responsible for the inefficient development of T and B cells from
      hESCs. hESCs and iPSCs, which can be engineered reliably in vitro, provide an
      important new model system to study human lymphocyte development and produce
      enhanced cell-based therapies with the potential to serve as a "universal" source
      of antitumor lymphocytes. This review will focus on the application of hESC
      derived NK cells with currently used and novel therapeutics for clinical trials,
      barriers to translation, and future applications through genetic engineering
      approaches.

PMID- 20801413
TI  - Stem cell technology for the treatment of acute and chronic renal failure.
AB  - Acute and chronic renal failure are disorders with high rates of morbidity and
      mortality. Current treatment is based upon conventional dialysis to provide
      volume regulation and small solute clearance. There is growing recognition that
      renal failure is a complex disease state requiring a multifactorial therapy to
      address the short-comings of the conventional monofactorial approach. Kidney
      transplantation remains the most effective treatment, however, organ availability
      lags far behind demand. Many key kidney functions including gluconeogenesis,
      ammoniagenesis, metabolism of glutathione, catabolism of important peptide
      hormones, growth factors, and cytokines critical to multiorgan homeostasis and
      immunomodulation are provided by renal tubule cells. Therefore, cell-based
      therapies are promising multifactorial treatment approaches. In this review,
      current stem cell technologies including adult stem cells, embryonic stem cells
      and induced pluripotent stem cells will be discussed as cell sources for the
      treatment of acute and chronic renal failure.

PMID- 20801414
TI  - Stem cell approaches for the treatment of type 1 diabetes mellitus.
AB  - Type 1 diabetes is characterized by near total absence of pancreatic b cells.
      Current treatments consisting of insulin injections and islet transplantation are
      clinically unsatisfactory. In order to develop a cure for type 1 diabetes, we
      must find a way to reverse autoimmunity, which underlies b cell destruction, as
      well as an effective strategy to generate new b cells. This article reviews the
      different approaches that are being taken to produce new b cells. Much emphasis
      has been placed on selecting the right non-b cell population, either in vivo or
      in vitro, as the starting material. Different cell types, including adult stem
      cells, other types of progenitor cells in situ, and even differentiated cell
      populations, as well as embryonic stem cells and induced pluripotent stem cells,
      will require different methods for islet and b cell induction. We discussed the
      pros and cons of the different strategies that are being used to re-invent the
      pancreatic b cell.

PMID- 20801415
TI  - Intestinal stem cells and epithelial-mesenchymal interactions in the crypt and
      stem cell niche.
AB  - The intestinal epithelium contains a rapidly proliferating and perpetually
      differentiating epithelium. The principal functional unit of the small intestine
      is the crypt-villus axis. Stem cells located in the crypts of Lieberkuhn give
      rise to proliferating progenitor or transit amplifying cells that differentiate
      into the 4 major epithelial cell types. The study of adult gastrointestinal tract
      stem cells has progressed rapidly with the recent discovery of several putative
      stem cell markers. Substantial evidence suggests 2 populations of stem cells:
      long-term quiescent (reserved) and actively cycling (primed) stem cells. These
      cells are in adjoining locations and are presumably maintained by the secretion
      of specific proteins generated in a unique microenvironment or stem cell niche
      surrounding each population. The relationship between these 2 populations, as
      well as the cellular sources and composition of the surrounding environment,
      remains to be defined, and is an active area of research. In this review, we will
      outline progress in identifying stem cells and in defining epithelial-mesenchymal
      interactions in the crypt. We will summarize early advances using stem cells for
      therapy of gastrointestinal disorders.

PMID- 20801418
TI  - New insights into the dynamics of cell adhesions.
AB  - Adhesion to the extracellular matrix (ECM) and to adjacent cells is a fundamental
      requirement for survival, differentiation, and migration of numerous cell types
      during both embryonic development and adult homeostasis. Different types of
      adhesion structures have been classified within different cell types or tissue
      environments. Much is now known regarding the complexity of protein composition
      of these critical points of cell contact with the extracellular environment. It
      has become clear that adhesions are highly ordered, dynamic structures under
      tight spatial control at the subcellular level to enable localized responses to
      extracellular cues. However, it is only in the last decade that the relative
      dynamics of these adhesion proteins have been closely studied. Here, we provide
      an overview of the recent data arising from such studies of cell-matrix and cell
      cell contact and an overview of the imaging strategies that have been developed
      and implemented to study the intricacies and hierarchy of protein turnover within
      adhesions.

PMID- 20801417
TI  - Use of virtual cell in studies of cellular dynamics.
AB  - The Virtual Cell (VCell) is a unique computational environment for modeling and
      simulation of cell biology. It has been specifically designed to be a tool for a
      wide range of scientists, from experimental cell biologists to theoretical
      biophysicists. The models created with VCell can range from the simple, to
      evaluate hypotheses or to interpret experimental data, to complex multilayered
      models used to probe the predicted behavior of spatially resolved, highly
      nonlinear systems. In this chapter, we discuss modeling capabilities of VCell and
      demonstrate representative examples of the models published by the VCell users.

PMID- 20801416
TI  - Stem cells and cell therapy approaches in lung biology and diseases.
AB  - Cell-based therapies with embryonic or adult stem cells, including induced
      pluripotent stem cells, have emerged as potential novel approaches for several
      devastating and otherwise incurable lung diseases, including emphysema, pulmonary
      fibrosis, pulmonary hypertension, and the acute respiratory distress syndrome.
      Although initial studies suggested engraftment of exogenously administered stem
      cells in lung, this is now generally felt to be a rare occurrence of uncertain
      physiologic significance. However, more recent studies have demonstrated
      paracrine effects of administered cells, including stimulation of angiogenesis
      and modulation of local inflammatory and immune responses in mouse lung disease
      models. Based on these studies and on safety and initial efficacy data from
      trials of adult stem cells in other diseases, groundbreaking clinical trials of
      cell-based therapy have been initiated for pulmonary hypertension and for chronic
      obstructive pulmonary disease. In parallel, the identity and role of endogenous
      lung progenitor cells in development and in repair from injury and potential
      contribution as lung cancer stem cells continue to be elucidated. Most recently,
      novel bioengineering approaches have been applied to develop functional lung
      tissue ex vivo. Advances in each of these areas will be described in this review
      with particular reference to animal models.

PMID- 20801420
TI  - Making senses development of vertebrate cranial placodes.
AB  - Cranial placodes (which include the adenohypophyseal, olfactory, lens, otic,
      lateral line, profundal/trigeminal, and epibranchial placodes) give rise to many
      sense organs and ganglia of the vertebrate head. Recent evidence suggests that
      all cranial placodes may be developmentally related structures, which originate
      from a common panplacodal primordium at neural plate stages and use similar
      regulatory mechanisms to control developmental processes shared between different
      placodes such as neurogenesis and morphogenetic movements. After providing a
      brief overview of placodal diversity, the present review summarizes current
      evidence for the existence of a panplacodal primordium and discusses the central
      role of transcription factors Six1 and Eya1 in the regulation of processes shared
      between different placodes. Upstream signaling events and transcription factors
      involved in early embryonic induction and specification of the panplacodal
      primordium are discussed next. I then review how individual placodes arise from
      the panplacodal primordium and present a model of multistep placode induction.
      Finally, I briefly summarize recent advances concerning how placodal neurons and
      sensory cells are specified, and how morphogenesis of placodes (including
      delamination and migration of placode-derived cells and invagination) is
      controlled.

PMID- 20801419
TI  - Axonal ensheathment and intercellular barrier formation in Drosophila.
AB  - Glial cells are critical players in every major aspect of nervous system
      development, function, and disease. Other than their traditional supportive role,
      glial cells perform a variety of important functions such as myelination, synapse
      formation and plasticity, and establishment of blood-brain and blood-nerve
      barriers in the nervous system. Recent studies highlight the striking functional
      similarities between Drosophila and vertebrate glia. In both systems, glial cells
      play an essential role in neural ensheathment thereby isolating the nervous
      system and help to create a local ionic microenvironment for conduction of nerve
      impulses. Here, we review the anatomical aspects and the molecular players that
      underlie ensheathment during different stages of nervous system development in
      Drosophila and how these processes lead to the organization of neuroglial
      junctions. We also discuss some key aspects of the invertebrate axonal
      ensheathment and junctional organization with that of vertebrate myelination and
      axon-glial interactions. Finally, we highlight the importance of intercellular
      junctions in barrier formation in various cellular contexts in Drosophila. We
      speculate that unraveling the genetic and molecular mechanisms of ensheathment
      across species might provide key insights into human myelin-related disorders and
      help in designing therapeutic interventions.

PMID- 20801421
TI  - Mechanisms of protein kinase A anchoring.
AB  - The second messenger cyclic adenosine monophosphate (cAMP), which is produced by
      adenylyl cyclases following stimulation of G-protein-coupled receptors, exerts
      its effect mainly through the cAMP-dependent serine/threonine protein kinase A
      (PKA). Due to the ubiquitous nature of the cAMP/PKA system, PKA signaling
      pathways underlie strict spatial and temporal control to achieve specificity. A
      kinase anchoring proteins (AKAPs) bind to the regulatory subunit dimer of the
      tetrameric PKA holoenzyme and thereby target PKA to defined cellular compartments
      in the vicinity of its substrates. AKAPs promote the termination of cAMP signals
      by recruiting phosphodiesterases and protein phosphatases, and the integration of
      signaling pathways by binding additional signaling proteins. AKAPs are a
      heterogeneous family of proteins that only display similarity within their PKA
      binding domains, amphipathic helixes docking into a hydrophobic groove formed by
      the PKA regulatory subunit dimer. This review summarizes the current state of
      information on compartmentalized cAMP/PKA signaling with a major focus on
      structural aspects, evolution, diversity, and (patho)physiological functions of
      AKAPs and intends to outline newly emerging directions of the field, such as the
      elucidation of AKAP mutations and alterations of AKAP expression in human
      diseases, and the validation of AKAP-dependent protein-protein interactions as
      new drug targets. In addition, alternative PKA anchoring mechanisms employed by
      noncanonical AKAPs and PKA catalytic subunit-interacting proteins are
      illustrated.

PMID- 20801422
TI  - Intestinal lymphangiectasia mimicking primary peritoneal carcinoma.
AB  - Intestinal lymphangiectasia is an obstruction of the lymphatic system. We report
      on a patient with mesenteric adenopathy and an elevated CA125 level, which were
      suspicious for peritoneal carcinoma. Further evaluation and bowel resection
      identified intestinal lymphangiectasia. This disease should be considered in
      patients with mesenteric adenopathy and a small bowel mass.

PMID- 20801424
TI  - Intravitreal injection of autologous plasmin enzyme for macular edema associated
      with branch retinal vein occlusion.
AB  - PURPOSE: To investigate the effects of an intravitreal injection of autologous
      plasmin enzyme for macular edema associated with a branch retinal vein occlusion
      (BRVO). DESIGN: Prospective, interventional case studies. METHODS: Twenty-six
      eyes of 26 patients (14 men and 12 women) with macular edema resulting from a
      BRVO were studied. None of the eyes had a posterior vitreous detachment (PVD).
      The average age at the onset of BRVO was 58.7 +/- 6.6 years. The interval between
      onset of the macular edema and injection of autologous plasmin enzyme was 4.2
      months. One international unit of autologous plasmin enzyme in 0.1 mL was
      injected into each vitreous. The presence of a PVD was evaluated 1 week after the
      injection, and the visual acuity and macular thickness were measured before and 1
      week and 1, 3, 6, and 12 months after the autologous plasmin enzyme injection.
      RESULTS: After the autologous plasmin enzyme injection, a total PVD was observed
      in 23 eyes and no PVD was observed in 3 eyes. The visual acuity gradually
      recovered after the injection, improved by 2 lines or more in 23 eyes, and
      remained unchanged in the 3 eyes. The retinal thickness also recovered gradually
      at 1, 3, 6, and 12 months. The mean retinal thickness was reduced from 602.12 to
      253.62 MUm at 12 months after surgery. It was reduced significantly after 1, 3,
      6, and 12 months (P < .0001). CONCLUSIONS: Intravitreal autologous plasmin enzyme
      may lead to an improvement of visual acuity and a reduction of macula edema in
      eyes with BRVO.

PMID- 20801423
TI  - Magnetic resonance imaging of tissues compatible with supernumerary extraocular
      muscles.
AB  - PURPOSE: To determine by magnetic resonance imaging (MRI) the prevalence and
      anatomy of anomalous extraocular muscle (EOM) bands. DESIGN: Prospective,
      observational case series. METHODS: High-resolution, multipositional, surface
      coil orbital MRI was performed using T1 or T2 fast spin echo weighting with
      target fixation control under a prospective protocol in normal adult subjects and
      a diverse group of strabismic patients between 1996 and 2009. Images
      demonstrating anomalous EOM bands were analyzed digitally to evaluate their sizes
      and paths, correlating findings with complete ophthalmic and motility
      examinations. RESULTS: Among 118 orthotropic and 453 strabismic subjects, 1
      (0.8%) orthotropic and 11 (2.4%) strabismic subjects exhibited unilateral or
      bilateral orbital bands having MRI signal characteristics identical to EOM. Most
      bands occurred without other EOM dysplasia and coursed in the retrobulbar space
      between rectus EOMs such as the medial rectus to lateral rectus, from superior to
      inferior rectus, or from 1 EOM to the globe. In 2 cases, horizontal bands from
      the medial rectus to lateral rectus muscles immediately posterior to the globe
      apparently limited supraduction by collision with the optic nerve. All bands were
      too deep to be approached via conventional strabismus surgical approaches.
      CONCLUSIONS: Approximately 2% of humans exhibit on MRI deep orbital bands
      consistent with supernumerary EOMs. Although band anatomy is nonoculorotary, some
      bands may cause restrictive strabismus.

PMID- 20801425
TI  - Stress distribution prevents ischaemia and bone resorption in residual ridge.
AB  - OBJECTIVE: Intensive mechanical stress and/or inflammation are known to induce
      alveolar bone resorption. This study investigated whether a distribution of
      mechanical stress would reduce residual ridge resorption or improve ischaemia.
      DESIGN: Thirty rats were divided into six experimental groups (n=5). The control
      group received no intentional stimulation, but rats in the experimental groups
      wore denture stimulators made of acrylic resin or a soft lining material. The
      stimulator transmitted masticatory pressure to the rats' palates for four weeks.
      The four types of soft lining materials investigated in this study dispersed the
      applied pressure, with compressive stress ranging from 20.8 to 90.8kPa. Volumes
      of blood flow and bone resorption of denture foundations were measured every week
      for 4 weeks. Statistical evaluation of these results was performed using two-way
      ANOVA and Holm-Sidak test within 5% error limits. RESULTS: Non-viscoelastic
      material clearly induced bone resorption and ischaemia of denture foundations,
      while viscoelastic materials reduced these phenomena to different extents
      according to their viscoelastic properties. Ischaemia in the alveolar ridge
      preceded residual ridge resorption, because the amount of residual ridge
      resorption and blood flow rate showed a simple linear regression. CONCLUSION:
      Animal model of this study suggested that a distribution or reduction of
      mechanical stress could improve blood flow and decrease alveolar ridge
      resorption.

PMID- 20801426
TI  - Fear and perceived uncontrollability of emotion: Evaluating the unique
      contribution of emotion appraisal variables to prediction of worry and
      generalised anxiety disorder.
AB  - Novel theoretical frameworks place the symptom profile of generalised anxiety
      disorder (GAD) within the context of dysfunctional emotional processes. It is
      suggested that fear and intolerance of emotions exacerbate subjective distress
      and motivate the use of maladaptive coping strategies, such as worry. To date,
      studies evaluating these models have suffered two key limitations. Firstly, few
      studies have involved treatment-seeking samples, and secondly, none have
      evaluated the unique variance attributable to emotion appraisal variables above
      and beyond previously established predictors of worry and GAD. The present study
      begins to address these limitations by assessing the contribution of fear and
      perceived uncontrollability of emotions in predicting worry and clinical GAD
      status after controlling for variance attributable to depressive symptoms, meta
      cognitive beliefs, intolerance of uncertainty, and perceptions of external
      threat. Supporting current models, results showed that perceived control over
      emotional reactions was a unique predictor of GAD diagnostic status and both
      clinical and non-clinical worry.

PMID- 20801427
TI  - Reduced gray matter volume of pars opercularis is associated with impaired social
      communication in high-functioning autism spectrum disorders.
AB  - BACKGROUND: Recent literature suggests that the inferior frontal gyrus,
      especially its posterior portion, has an important role in imitation and social
      reciprocity and in the pathophysiology of their disturbance in autism spectrum
      disorders (ASD). However, the structural abnormality of this region has not fully
      been clarified in subjects with ASD. METHODS: Here we obtained magnetic resonance
      images from 13 right-handed men with high-functioning ASD (Asperger disorder [n =
      10] or autism [n = 3]) and from 11 age-, parental socioeconomic background-, and
      intelligence quotient-matched right-handed typical men. A reliable manual tracing
      methodology was employed to measure the gray matter volume of the pars
      opercularis, corresponding to Brodmann area 44, and the pars triangularis,
      corresponding to Brodmann area 45. RESULTS: A significant gray matter volume
      reduction of both the pars opercularis and triangularis was found bilaterally in
      the subjects with ASD compared with the typical control subjects. The effect size
      seemed to be larger for pars opercularis (1.25) than for pars triangularis (.90).
      The reduced volume of right as well as total pars opercularis showed a
      significant association with the increased severity of social communication
      problems in the ASD group. CONCLUSIONS: The current findings support an important
      role of pars opercularis, a center of the mirror neuron system, in the
      pathophysiology of ASD.

PMID- 20801429
TI  - Cocaine-insensitive dopamine transporters with intact substrate transport
      produced by self-administration.
AB  - BACKGROUND: Psychomotor stimulant drugs such as cocaine and amphetamine activate
      brain dopamine (DA) neurotransmission and support self-administration in humans
      and laboratory animals. Cocaine amplifies DA signaling by blocking the DA
      transporter (DAT), and this has been described as the most important mechanism
      underlying cocaine's reinforcing effects. Amphetamine has the added mechanism of
      reverse transport of intracellular DA through the DAT. METHODS: We used cocaine
      and amphetamine self-administration under a fixed-ratio 1 schedule followed by
      microdialysis in freely moving rats to measure extracellular DA levels and fast
      scan cyclic voltammetry in brain slices to measure subsecond DA release and
      uptake parameters. RESULTS: Following a high dose (1.5 mg/kg intravenous) cocaine
      self-administration paradigm (40 injections/day * 5 days), the DAT was markedly
      less sensitive to cocaine, as measured by microdialysis and voltammetry in the
      nucleus accumbens core. In contrast, the DAT substrate amphetamine retained the
      same efficacy at the DAT in cocaine self-administering animals, and amphetamine
      did not mimic cocaine's effect on the DAT when self-administered. A single
      session of cocaine self-administration caused a significant decrease in the
      ability of cocaine to inhibit the DAT, a finding that may provide a neurochemical
      basis for rapid tolerance. The effects of cocaine returned to normal within a few
      weeks following cessation of self-administration. CONCLUSIONS: Here, we, for the
      first time, demonstrate an in vivo, pharmacologically induced alteration in the
      sensitivity of the DAT to cocaine that is specific to cocaine, spares DAT and
      substrate/releaser interactions, and is independent of maximal rate of DA uptake
      (V(max)).

PMID- 20801428
TI  - Analyzing schizophrenia by DNA microarrays.
AB  - To understand the pathological processes of schizophrenia, we must embrace the
      analysis of the diseased human brain: we will never be able to recapitulate the
      pathology of uniquely human disorders in an animal model. Based on the outcome of
      the transcriptome profiling experiments performed to date, it appears that
      schizophrenia is associated with a global gene expression disturbance across many
      cortical regions. In addition, transcriptome changes are present in multiple cell
      types, including specific subclasses of principal neurons, interneurons, and
      oligodendrocytes. Furthermore, transcripts related to synaptic transmission,
      energy metabolism, and inhibitory neurotransmission are routinely found
      underexpressed in the postmortem brain tissue of subjects with schizophrenia. To
      put these transcriptome data in biological context, we must make our data
      publicly available and report our findings in a proper, expanded Minimum
      Information About a Microarray Experiment format. Cell-type specific expression
      profiling and sequencing-based transcript assessments should be expanded, with
      particular attention to understanding splice-variant changes in various mental
      disorders. Deciphering the pathophysiology of mental disorders depends on
      integrating data from across many research fields and techniques. Leads from
      postmortem transcriptome profiling will be essential to generate model animals,
      perform tissue culture experiments, and develop or evaluate novel drugs to treat
      this devastating disorder.

PMID- 20801431
TI  - Synthesis and inhibition properties of a series of pyranose derivatives towards a
      Zn-metalloproteinase from Saccharomonospora canescens.
AB  - The Zn-proteinase, isolated from Saccharomonospora canescens (NPS), shares many
      common features with thermolysin, but considerable differences are also evident,
      as far as the substrate recognition site is concerned. In substrates of general
      structure AcylAlaAlaPhe 4NA, this neutral proteinase cleaves only the arylamide
      bond (non-typical activity of Zn-proteinases), while thermolysin attacks the
      peptide bond Ala-Phe. Phosphoramidon is a powerful tight binding inhibitor for
      thermolysin and significantly less specific towards NPS. The K(i)-values (65 MUM
      for NPS vs 0.034 MUM for thermolysin) differ nearly 2000-folds. This implies
      significant differences in the specificity of the corresponding subsites. The
      carbohydrate moiety is supposed to accommodate in the S1-subsite and the series
      of arabinopyranosides and glucopyranosides (12 compounds), which are assayed as
      inhibitors in a model system: NPS with SucAlaAlaPhe4NA as a substrate could be
      considered as mapping the S1-subsite of NPS. Members of the series with an
      additional ring (3,4-epithio, 3,4-anhydro-derivatives) turned out to be
      reasonably good competitive inhibitors (K(i)~0.1-0.2 mM are of the same order as
      the K(i) value for phosphoramidon). The structure of these compounds (8, 9, 11
      and 12) seems to fit the size of the S1-subsite and due to an appropriately
      oriented OH-group in addition, to protect the active site Zn(2+).

PMID- 20801432
TI  - Wheat gluten-based renewable and biodegradable polymer materials with enhanced
      hydrophobicity by using epoxidized soybean oil as a modifier.
AB  - Epoxidized soybean oil (ESO) was applied as an additive for wheat gluten (WG) to
      modify the properties of the renewable and biodegradable natural polymer
      materials. Optimum intermolecular interactions and crosslinking between ESO
      chains and the WG matrix were achieved under alkaline conditions. The WGESO
      materials were heterogeneous on a scale of 20-30 nm, but the homogeneity was
      improved upon increasing the amount of glycerol as a plasticizer in the
      materials. The combination of plasticization and crosslinking effects derived
      from ESO resulted in good retention in mechanical strength for the plasticized
      WGESO materials as compared to those without 10 wt% of mobile ESO additives. The
      hydrophobicity of the plasticized WG materials was also enhanced significantly by
      using the ESO additives.

PMID- 20801430
TI  - Blockade of nicotine reward and reinstatement by activation of alpha-type
      peroxisome proliferator-activated receptors.
AB  - BACKGROUND: Recent findings indicate that inhibitors of fatty acid amide
      hydrolase (FAAH) counteract the rewarding effects of nicotine in rats. Inhibition
      of FAAH increases levels of several endogenous substances in the brain, including
      the endocannabinoid anandamide and the noncannabinoid fatty acid ethanolamides
      oleoylethanolamide (OEA) and palmitoylethanolamide, which are ligands for alpha
      type peroxisome proliferator-activated nuclear receptors (PPAR-alpha). Here, we
      evaluated whether directly acting PPAR-alpha agonists can modulate reward-related
      effects of nicotine. METHODS: We combined behavioral, neurochemical, and
      electrophysiological approaches to evaluate effects of the PPAR-alpha agonists
      [[4-Chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]thio]acetic acid (WY14643)
      and methyl oleoylethanolamide (methOEA; a long-lasting form of OEA) on 1)
      nicotine self-administration in rats and squirrel monkeys; 2) reinstatement of
      nicotine-seeking behavior in rats and monkeys; 3) nicotine discrimination in
      rats; 4) nicotine-induced electrophysiological activity of ventral tegmental area
      dopamine neurons in anesthetized rats; and 5) nicotine-induced elevation of
      dopamine levels in the nucleus accumbens shell of freely moving rats. RESULTS:
      The PPAR-alpha agonists dose-dependently decreased nicotine self-administration
      and nicotine-induced reinstatement in rats and monkeys but did not alter food- or
      cocaine-reinforced operant behavior or the interoceptive effects of nicotine. The
      PPAR-alpha agonists also dose-dependently decreased nicotine-induced excitation
      of dopamine neurons in the ventral tegmental area and nicotine-induced elevations
      of dopamine levels in the nucleus accumbens shell of rats. The ability of WY14643
      and methOEA to counteract the behavioral, electrophysiological, and neurochemical
      effects of nicotine was reversed by the PPAR-alpha antagonist 1-[(4
      Chlorophenyl)methyl]-3-[(1,1-dimethylethyl)thio]-a,a-dimethyl-5-(1-methylethyl)
      1H-Indole-2-propanoic acid (MK886). CONCLUSIONS: These findings indicate that
      PPAR-alpha might provide a valuable new target for antismoking medications.

PMID- 20801433
TI  - Repeated speech errors: evidence for learning.
AB  - Three experiments elicited phonological speech errors using the SLIP procedure to
      investigate whether there is a tendency for speech errors on specific words to
      reoccur, and whether this effect can be attributed to implicit learning of an
      incorrect mapping from lemma to phonology for that word. In Experiment 1, when
      speakers made a phonological speech error in the study phase of the experiment
      (e.g. saying "beg pet" in place of "peg bet") they were over four times as likely
      to make an error on that same item several minutes later at test. A pseudo-error
      condition demonstrated that the effect is not simply due to a propensity for
      speakers to repeat phonological forms, regardless of whether or not they have
      been made in error. That is, saying "beg pet" correctly at study did not induce
      speakers to say "beg pet" in error instead of "peg bet" at test. Instead, the
      effect appeared to be due to learning of the error pathway. Experiment 2
      replicated this finding, but also showed that after 48 h, errors made at study
      were no longer more likely to reoccur. As well as providing constraints on the
      longevity of the effect, this provides strong evidence that the error
      reoccurrences observed are not due to item-specific difficulty that leads
      individual speakers to make habitual mistakes on certain items. Experiment 3
      showed that the diminishment of the effect 48 h later is not due to specific
      extra practice at the task. We discuss how these results fit in with a larger
      view of language as a dynamic system that is constantly adapting in response to
      experience.

PMID- 20801434
TI  - Causal-explanatory pluralism: How intentions, functions, and mechanisms influence
      causal ascriptions.
AB  - Both philosophers and psychologists have argued for the existence of distinct
      kinds of explanations, including teleological explanations that cite functions or
      goals, and mechanistic explanations that cite causal mechanisms. Theories of
      causation, in contrast, have generally been unitary, with dominant theories
      focusing either on counterfactual dependence or on physical connections. This
      paper argues that both approaches to causation are psychologically real, with
      different modes of explanation promoting judgments more or less consistent with
      each approach. Two sets of experiments isolate the contributions of
      counterfactual dependence and physical connections in causal ascriptions
      involving events with people, artifacts, or biological traits, and manipulate
      whether the events are construed teleologically or mechanistically. The findings
      suggest that when events are construed teleologically, causal ascriptions are
      sensitive to counterfactual dependence and relatively insensitive to the presence
      of physical connections, but when events are construed mechanistically, causal
      ascriptions are sensitive to both counterfactual dependence and physical
      connections. The conclusion introduces an account of causation, an "exportable
      dependence theory," that provides a way to understand the contributions of
      physical connections and teleology in terms of the functions of causal
      ascriptions.

PMID- 20801435
TI  - On subjective time.

PMID- 20801436
TI  - The effect of transdermal testosterone gel pretreatment on controlled ovarian
      stimulation and IVF outcome in low responders.
AB  - OBJECTIVE: To investigate the effectiveness of treatment with transdermal
      testosterone gel (TTG) before controlled ovarian stimulation (COS) using GnRH
      antagonist multiple-dose protocol (MDP) in low responders undergoing
      IVF/intracytoplasmic sperm injection (ICSI). DESIGN: Prospective randomized
      controlled trial. SETTING: University-affiliated infertility clinic. PATIENT(S):
      A total of 110 low responders, who were defined as patients who failed to produce
      <= 3 follicles with a mean diameter of >= 16 mm with the result that <= 3 oocytes
      were retrieved despite the use of a high gonadotropin dose (>2,500 IU) in a
      previous failed IVF/ICSI cycle. INTERVENTION(S): Patients were randomized into
      TTG pretreatment group or control group. For TTG pretreatment group, 12.5 mg TTG
      were applied daily for 21 days in the cycle preceding COS for IVF. MAIN OUTCOME
      MEASURE(S): COS results and IVF outcome. RESULT(S): There were no differences in
      patients' characteristics between the two groups. Total dose and days of rhFSH
      used were significantly fewer in the TTG pretreatment group than in the control
      group. The numbers of oocytes retrieved, mature oocytes, fertilized oocytes, and
      good-quality embryos were significantly higher in the TTG pretreatment group.
      Embryo implantation rate and clinical pregnancy rate per cycle initiated also
      were significantly higher in the women pretreated with TTG. No patient reported
      adverse effects attributed to TTG use. CONCLUSION(S): TTG pretreatment might be
      beneficial in improving both response to COS and IVF outcome in low responders
      undergoing IVF/ICSI.

PMID- 20801437
TI  - Which are the ideal donor and recipient vessels for a whole ovarian
      transplantation?
AB  - OBJECTIVE: To compare deep circumflex iliac (DCI) and deep inferior epigastric
      (DIE) pedicles as potential recipient vessels for a whole ovarian microvascular
      transplantation. DESIGN: Anatomical study. SETTING: Laboratory of anatomy,
      university center. PATIENT(S): Ten fresh human female cadavers. INTERVENTION(S):
      Anatomical dissections, vascular injections, histologic analysis. MAIN OUTCOME
      MEASURE(S): Morphological analysis of the gonadic, DCI, and DIE pedicles;
      diameter of the vessels at regular intervals along their entire length.
      Comparisons of the caliber values between receiving (DCI and DIE) and gonadic
      pedicles aiming to determine the optimal size match. RESULT(S): We highlight a
      tortuous appearance of the gonadic artery. This morphology contrasted with the
      venous system that included two or three straight veins, one of them being wider
      than the others. The gonadic vessels converge into a wider artery and vein at 5
      cm from the ovary. An optimal size match existed between gonadic and DCI arteries
      and veins sections, in 13 of 14 gonadic pedicles. CONCLUSION(S): A safe
      microsurgical whole ovarian transplantation is feasible if the gonadic pedicle is
      harvested with a minimal length of 5 cm from the ovary. The DCI pedicle seems to
      have the best size match with the ovarian vessels to perform a reliable end-to
      end microvascular anastomosis.

PMID- 20801438
TI  - SEPT12 deficiency causes sperm nucleus damage and developmental arrest of
      preimplantation embryos.
AB  - Oocytes fertilized with spermatozoa obtained from Septin 12+/- chimeric mice
      failed to develop beyond the morula stage after IVF and intracytoplasmic sperm
      injection because of significant DNA defects in the spermatozoa. Given that
      SEPT12 is expressed at the edge of the sperm nucleus in both humans and mice, we
      hypothesized the vital roles of Septin 12 in sperm head shaping, nuclear DNA
      condensation, and early embryonic development.

PMID- 20801439
TI  - GnRH-agonist induced depressive and anxiety symptoms during in vitro
      fertilization-embryo transfer cycles.
AB  - To determine whether the use of a GnRH agonist inducing a hypogonadic state
      during IVF-ET cycles induces negative mood symptoms, we conducted a prospective
      randomized study in 108 women comparing two different controlled ovarian
      stimulation protocols. A significant phase effect was observed for depression and
      anxiety symptoms during IVF-ET cycles reflecting an increase in symptoms between
      the hypogonadal phase and the peak in gonadotropin stimulation; however, the
      hypogonadal phase induced by the GnRH agonist was not associated with a
      significant increase in any of the studied mood parameters.

PMID- 20801440
TI  - Detection of Hodgkin lymphoma within ovarian tissue.
AB  - OBJECTIVE: To describe the detection of Hodgkin lymphoma within ovarian tissue
      taken at the time of harvest for cryopreservation. DESIGN: Case report. SETTING:
      University-affiliated women's hospital. PATIENT(S): A 19-year-old woman diagnosed
      with Hodgkin lymphoma. INTERVENTION(S): Laparoscopic removal of ovarian tissue
      for cryopreservation. MAIN OUTCOME MEASURE(S): Histologic and immunohistochemical
      evaluation of ovarian tissue harvested for fertility preservation. RESULT(S):
      Histologic and immunohistochemical identification of Hodgkin lymphoma within
      ovarian tissue harvested for cryopreservation. CONCLUSION(S): Ovarian
      cryopreservation and subsequent autografting is a procedure still in an
      experimental phase that has yielded promising findings. This option is frequently
      offered to young women with neoplasms such as Hodgkin lymphoma. Although the risk
      of Hodgkin lymphoma infiltration into the ovary may be low, the identification of
      lymphoma in this case emphasizes the importance of histologic examination of
      ovarian tissue before freezing and indicates that there is a possibility of
      reintroducing tumor.

PMID- 20801441
TI  - Four spontaneous pregnancies and three live births following subcutaneous
      transplantation of frozen banked ovarian tissue: what is the explanation?
AB  - OBJECTIVE: To report the long-term follow-up of an experimental heterotopic
      ovarian transplantation with frozen-thawed ovarian tissue. DESIGN: Long-term
      follow-up of an experimental surgery; case report. SETTING: Academic reproductive
      medicine center. PATIENT(S): A 28-year-old cancer survivor with previous Hodgkin
      disease and relapse. INTERVENTION(S): Laparoscopic oophorectomy for ovarian
      cryopreservation before preconditioning chemotherapy for hematologic stem cell
      transplantation. Ovarian tissue thawing and subcutaneous heterotopic ovarian
      transplantation in the lower abdominal wall 21/2 years after the hematologic stem
      cell transplantation. MAIN OUTCOME MEASURE(S): Resumption of ovarian function
      after transplantation, recovery of fertility, and pregnancy outcome. RESULT(S):
      Follicle development was observed in the graft 2 months after transplantation,
      and a P value of 14 ng/mL indicated ovulation. The patient conceived
      spontaneously four times within 5 years and delivered three children. The in situ
      ovary remained atrophic but showed occasional follicle activity contemporaneously
      with the graft. CONCLUSION(S): The mechanism behind spontaneous restoration of
      fertility with consecutive viable pregnancies after a heterotopic ovarian
      transplantation needs to be explored. Further laboratory and clinical research
      will be needed to explore the true origin of pregnancies after ovarian
      transplantations.

PMID- 20801442
TI  - Cranial vault shape in fossil hominids: Fourier descriptors in norma lateralis.
AB  - Two major views of human evolution have elicited considerable controversy. These
      are: [1] the "out of Africa" hypothesis and [2] the "multiregional" hypothesis.
      This paper is an attempt to try to reconcile these two scenarios using hominid
      cranial vault data. Elliptical Fourier functions (EFFs) were used to describe, in
      visual and numerical terms, the shape of the human cranial vault in norma
      lateralis. Using jpeg images, contours of the cranial vault of a large sample of
      hominid specimens were pre-processed in Photoshop CS and rotated in 2D space
      (positional-orientation) so that a line drawn from nasion to porion was
      horizontal. The cranial vault image was then digitized with 72 closely-spaced
      points and submitted to a specially written routine that computed EFFs normalized
      by scaling (size-standardization). This ensured that the representation was
      invariant with respect to starting point, size and orientation. Statistically
      significant differences were found between the H. sapiens sample and both the H.
      erectus and H. neanderthalensis samples. In contrast, there were no statistically
      significant differences between the H. erectus and H. neanderthalensis groups,
      leading to three conclusions: [1] the similarity in cranial vault shape between
      H. erectus and H. neanderthalensis suggests a single gradually evolving lineage;
      [2] The taxon H. heidelbergensis can be embedded into the H. erectus->H.
      neanderthalensis line; and [3] H. sapiens seems to be a separate evolutionary
      development and is considered here either as a separate species or as a possible
      example of an allopatric semispecies (Grant, 1977). The results here suggest that
      human evolution over the last 2 Ma may turn out to be neither totally
      multiregional or simply out of Africa but rather represents a considerably more
      complicated picture.

PMID- 20801443
TI  - Disclosing adverse outcomes in medical care: FIGO Committee for the Ethical
      Aspects of Human Reproduction and Women's Health.

PMID- 20801444
TI  - A randomized controlled trial of 400-MUg sublingual misoprostol versus manual
      vacuum aspiration for the treatment of incomplete abortion in two Egyptian
      hospitals.
AB  - OBJECTIVE: To compare the safety, efficacy, and acceptability of 400-MUg
      sublingual misoprostol with that of manual vacuum aspiration (MVA) in 2 Egyptian
      hospitals. METHODS: Participating women were randomized to either MVA or
      misoprostol treatment for incomplete abortion. The primary outcome, complete
      uterine evacuation, was determined 1 week later, as were adverse effects, change
      in hemoglobin, acceptability, and satisfaction. RESULTS: Complete uterine
      evacuation was achieved in 98.3% of women who received misoprostol and 99.7% who
      underwent MVA (relative risk [RR] 0.99; 95% confidence interval [CI], 0.97-1.00).
      A decrease in hemoglobin of 2g/dL or more was comparably rare in the 2 groups
      (0.3% misoprostol vs 0.9% MVA; RR 0.34 [95% CI, 0.04-3.21]). Mean change in
      hemoglobin was also clinically similar (-0.5 g/dL misoprostol vs -0.4 g/dL MVA;
      P<0.01). Heavy bleeding was rare (2.4% misoprostol vs 1.6% MVA; RR 1.55 [95% CI,
      0.51-4.68]) following treatment. Nearly all women (96.8% misoprostol vs 98.3%
      MVA) were satisfied with their treatment but those who received misoprostol were
      significantly more likely to prefer that method in the future (81.9% vs 62.8%; RR
      1.30 [95% CI, 1.19-1.43]). CONCLUSION: The high efficacy, safety, and
      acceptability of 400-MUg sublingual misoprostol indicate that it is analogous to
      surgery as a first-line treatment for incomplete abortion. Misoprostol might
      improve post-abortion care when resources are limited and surgical treatment is
      unavailable.

PMID- 20801445
TI  - Domestic violence during pregnancy reported by women attending a university
      teaching hospital in Nigeria for antenatal care.

PMID- 20801446
TI  - Lactobacillus rhamnosus GR-1 and L. reuteri RC-14 to prevent or cure bacterial
      vaginosis among women with HIV.
AB  - OBJECTIVE: To assess, among women with HIV, whether long-term oral Lactobacillus
      rhamnosus GR-1 and Lactobacillus reuteri RC-14 supplementation can prevent
      bacterial vaginosis (BV) and enhance the cure rate of metronidazole among those
      with BV. METHODS: A randomized, double-blind, placebo-controlled trial conducted
      among 65 HIV-infected women with an aberrant microbiota (Nugent score 4-10) who
      were randomized to receive daily probiotics or placebo for 6 months. Those with
      BV (Nugent score 7-10) additionally received metronidazole for 10 days (400 mg
      twice daily). RESULTS: We did not find an enhanced cure rate of BV among women
      with HIV treated with adjuvant probiotics to metronidazole treatment. Among women
      with an intermediate vaginal flora, probiotics tended to increase the probability
      of a normal vaginal flora (odds ratio 2.4; P=0.1) and significantly increased the
      probability of a beneficial vaginal pH (odds ratio 3.8; P=0.02) at follow-up.
      CONCLUSION: Supplementation of probiotic L. rhamnosus GR-1 and L. reuteri RC-14
      did not enhance the cure of BV among women living with HIV, but may prevent the
      condition among this population. TRIAL REGISTRATION: NCT00536848.

PMID- 20801447
TI  - Cytology versus visual inspection with acetic acid among women treated previously
      with cryotherapy in a low-resource setting.
AB  - OBJECTIVE: To compare visual inspection with acetic acid (VIA) with conventional
      cervical cytology as a follow-up cervical cancer screening method in women who
      had been treated previously with cryotherapy. METHODS: Salvadoran women screened
      with VIA and treated with cryotherapy within 3 years were eligible to
      participate. Study participants were rescreened with VIA, Pap smear, colposcopy,
      4-quandrant biopsy, and endocervical curettage. RESULTS: Of 147 women enrolled in
      the study, post-cryotherapy VIA was positive in 39 women (26.5%; 95% CI, 19.6%
      34.4%). Of these 39, 1 woman had CIN 1 or higher on biopsy. Post-cryotherapy Pap
      smear was positive (ASCUS or higher) in 6 women (4.1%; 95% CI, 1.5%-8.7%). Of
      these 6, 2 women had CIN 1 or higher on biopsy. Post-cryotherapy specificity was
      significantly higher for Pap compared with VIA (95.8% [138/144]; 95% CI, 91.2%
      98.5% vs 73.6% [106/144]; 95% CI, 65.6%-80.6%; P<0.001). CONCLUSION: As the
      single-visit approach for cervical cancer screening gains popularity, more women
      will have been treated with cryotherapy. Appropriate follow-up screening is
      therefore vital. Cytology may be a more suitable screening method than VIA in low
      resource settings for women treated previously with cryotherapy.

PMID- 20801448
TI  - Cross-border reproductive services: FIGO Committee for the Ethical Aspects of
      Human Reproduction and Women's Health.

PMID- 20801449
TI  - Outcomes for pregnant women infected with the influenza A (H1N1) virus during the
      2009 pandemic in Porto Alegre, Brazil.
AB  - OBJECTIVE: To study the epidemiologic characteristics and underlying conditions
      that place pregnant women infected with H1N1 virus at increased risk for being
      admitted to the intensive care unit (ICU). METHODS: In this cross-sectional study
      conducted in Porto Alegre, Brazil, with 57 pregnant women hospitalized with the
      H1N1 influenza during the 2009 pandemic, we collected epidemiologic
      characteristics and assessed the rates of ICU admission according to pregnancy
      duration and the presence or absence of comorbidities. RESULTS: The median
      (range) of maternal age was 26 years (15-41 years), the pregnancy duration at the
      time of infection was 29 weeks (8-41 weeks), and the birth weight was 3180 g (740
      3900 g). Five patients (8.8%) were in the first, 22 (38.6%) in the second, and 30
      (52.6%) in the third trimester, and (22.8%) had comorbidities. Antiviral drugs
      were administered to all, and 46 (80.7%) patients received an early treatment.
      There were no maternal, fetal, or neonatal deaths. Eight patients (14%) required
      ICU admission and 15 (50%) of the patients who gave birth during their
      hospitalization underwent a cesarean delivery. The risk of being treated at the
      ICU did not increase for patients with comorbidities (P=0.22) or an advanced
      pregnancy (P=0.31). The study revealed a relationship between early initiation of
      an antiviral treatment and a lower mortality rate. CONCLUSION: Neither an
      advanced pregnancy nor comorbidities increased the risk of being admitted to the
      ICU but, compared with the results of other studies, a prompt treatment lowered
      mortality.

PMID- 20801450
TI  - A 'good hospital': nurse and patient perceptions of good clinical care for HIV
      positive people on antiretroviral treatment in rural Zimbabwe--a mixed-methods
      qualitative study.
AB  - BACKGROUND: Antiretroviral treatment for HIV is gradually being made available
      across sub-Saharan Africa. With antiretroviral treatment, HIV can be approached
      as a chronic, manageable condition rather than a shorter-term issue of palliative
      care. This treatment involves repeated interaction between health staff and
      patients for ongoing check-ups and prescription refills. OBJECTIVE: This study
      aimed to understand patient and healthcare staff perceptions of good clinical
      antiretroviral treatment care. DESIGN: Over 100 h of ethnographic observation at
      healthcare sites; interviews and focus groups with 25 healthcentre workers
      (mostly nurses), 53 HIV-positive adults taking ARVs and 40 carers of children on
      ART. The data were analyzed using thematic content analysis. SETTING: Three
      healthcare sites providing free antiretroviral drugs in rural Zimbabwe, where the
      adult HIV infection rate is approximately 20%. RESULTS: Contrary to reports of
      poor antiretroviral treatment adherence and task-oriented rather than patient
      oriented nursing, our study found great patient commitment to adherence,
      outstanding nurse dedication and a pervasive sense of hope about coping with HIV.
      Within this context however there were some situations where patients and nurses
      had different expectations of the medical encounter, leading to stress and
      dissatisfaction. Patients and staff both emphasized the importance of nurse
      kindness, understanding, confidentiality and acceptance (i.e. treating HIV
      patients 'like normal') and patient adherence to medical directions. However,
      nurses at times overlooked the negative effects of long wait times and frequent
      hospital visits. Further, nurses sometimes conflated medical adherence with
      general patient obedience in all aspects of the nurse-patient relationships.
      Patients and staff were frustrated by the ambiguity and unpredictability
      surrounding key elements of hospital visits such as how much patients had to pay
      for service, how long it would take to be served, and whether drugs or the
      doctor's services would be available.

PMID- 20801452
TI  - Determination of toe-off event time during treadmill locomotion using kinematic
      data.
AB  - Researchers collecting gait kinematic data during treadmill locomotion are often
      interested in determining the times of toe off and heel strike for each stride.
      In the absence of additional hardware, only position data collected with motion
      capture equipment may be available. Others have published methods for using
      kinematic data for detecting overground gait events. However, during treadmill
      locomotion, especially running, overground methods may not possess sufficient
      accuracy. The purpose of this paper is to describe a method for using kinematic
      data to determine the time of toe off during treadmill locomotion. Ten subjects
      walked and ran on a treadmill while a motion-capture system collected positional
      data from heel and toe markers. The treadmill was equipped with force platforms
      that allowed an accurate determination of foot-ground contact. The time of toe
      off was determined using the vertical component of the toe marker, and this
      method was found to have greater accuracy for event detection than other
      published methods. Researchers can use the described method to determine times of
      heel strike and toe off during treadmill locomotion using only kinematic data.

PMID- 20801451
TI  - Association of epicardial adipose tissue with coronary atherosclerosis is region
      specific and independent of conventional risk factors and intra-abdominal
      adiposity.
AB  - OBJECTIVE: To elucidate which measurement of epicardial adipose tissue (EAT) best
      reflects its atherogenic risk, we examined the associations between different EAT
      measurements and various atherosclerotic parameters of the entire coronary tree
      and individual coronary arteries. METHODS: This study included 224 consecutive
      patients underwent multidetector computed tomography before diagnostic coronary
      angiography. Regional thickness, cross-sectional areas, and total volume of EAT
      were measured. Four atherosclerotic parameters, including severity score, extent
      score, calcium volume score, and number of coronary arteries with >=50% luminal
      stenosis, of the entire coronary tree and individual coronary arteries were
      assessed. RESULTS: Both total EAT volume and thickness of EAT in the left
      atrioventricular groove were unanimously associated with the presence of coronary
      atherosclerosis dichotomously defined by the 4 scoring systems. However, only EAT
      thickness in the left atrioventricular groove, but not total EAT volume, was
      significantly associated with all 4 parameters of coronary atherosclerosis in a
      dose-dependent manner, even after adjustments for conventional risk factors, body
      mass index, waist circumference, C-reactive protein, and intra-abdominal visceral
      fat area. Using the receiver-operating-characteristic analysis, 12.2mm was the
      optimal cutoff point for left atrioventricular groove thickness to predict the
      presence of significant coronary stenosis (>=50% diameter stenosis). Among the
      three coronary arteries, left atrioventricular groove thickness was most strongly
      correlated with >=50% diameter stenosis in the embedded left circumflex artery by
      multivariate regression model. CONCLUSIONS: Thickness of EAT in the left
      atrioventricular groove provides a more accurate assessment of its atherogenic
      risk and is therefore a better coronary risk factor than total EAT volume.

PMID- 20801453
TI  - Thermal effect on heart rate and hemodynamics in vitelline arteries of stage 18
      chicken embryos.
AB  - We investigated the thermal effects on heart rate, hemodynamics, and response of
      vitelline arteries of stage-18 chicken embryos. Heart rate was monitored by a
      high-speed imaging method, while hemodynamic quantities were evaluated using a
      particle image velocimetry (PIV) technique. Experiments were carried out at seven
      different temperatures (36-42  degrees C with 1  degrees C interval) after 1h of
      incubation to stabilize the heart rate. The heart rate increased in a linear
      manner (r = 0.992). Due to the increased cardiac output (or heart rate), the
      hemodynamic quantities such as mean velocity (U(mean)), velocity fluctuation
      (U(fluc)), and peak velocity (U(peak)) also increased with respect to the
      Womersley number (Omega) in the manner r = 0.599, 0.693, and 0.725, respectively.
      This indicates that the mechanical force exerting on the vessel walls increases.
      However, the active response (or regulation) of the vitelline arteries was not
      observed in this study.

PMID- 20801454
TI  - Interpreting the difference between conventional and bi-directional plate-height
      measurements in liquid chromatography.
AB  - An experimental and theoretical study was conducted of the column
      characterization technique in which plate heights determined using the
      conventional pulse-response method are compared with those determined using a bi
      directional method where an eluite sample is introduced into one end of a
      chromatographic column and elution occurs at the same end after the flow
      direction is reversed inside the column. Experiments are presented for a
      micropellicular HPLC column before and after its performance has been degraded by
      repeated sample injections, for a low-pressure column containing nonporous glass
      particles, and for an HPLC column containing particles with 300 A pores. The
      results obtained are interpreted in terms of several different theories which
      apply in various Fourier number ranges. It was shown that the transcolumn
      contribution to convective dispersion in a chromatographic column is largely
      responsible for the difference observed between conventional and bi-directional
      plate-height measurements and that a collocation method can be employed to
      develop a useful analytical expression for this contribution.

PMID- 20801455
TI  - A generic static headspace gas chromatography method for determination of
      residual solvents in drug substance.
AB  - In order to increase productivity of drug analysis in the pharmaceutical
      industry, an efficient and sensitive generic static headspace gas chromatography
      (HSGC) method was successfully developed and validated for the determination of
      44 classes 2 and 3 solvents of International Conference of Harmonization (ICH)
      guideline Q3C, as residual solvents in drug substance. In order to increase the
      method sensitivity and efficiency in sample equilibration, dimethylsulfoxide
      (DMSO) was selected as the sample diluent based on its high capacity of
      dissolving drug substance, stability and high boiling point. The HS sample
      equilibration temperature and equilibration time are assessed in ranges of 125
      150 degrees C and 8-15 min, respectively. The results indicate that the residual
      solvents in 200mg of drug substance can be equilibrated efficiently in HS sampler
      at 140 degrees C for 10 min. The GC parameters, e.g. sample split ratio, carrier
      flow rate and oven temperature gradient are manipulated to enhance the method
      sensitivity and separation efficiency. The two-stage gradient GC run from 35 to
      240 degrees C, using an Agilent DB-624 capillary column (30 m long, 0.32 mm I.D.,
      1.8 MUm film thickness), is suitable to determine 44 ICH classes 2 and 3 solvents
      in 30 min. The method validation results indicate that the method is accurate,
      precise, linear and sensitive for solvents assessed. The recoveries of most of
      these solvents from four drug substances are greater than 80% within the method
      determination ranges. However, this method is not suitable for the 10 remaining
      ICH classes 2 and 3 solvents, because they are too polar (e.g. formic acid and
      acidic acid), or have boiling points higher than 150 degrees C, (e.g. anisol and
      cumene). In comparison with the previous published methods, this method has a
      much shorter sample equilibration time, a better separation for many solvents, a
      higher sensitivity and a broader concentration range.

PMID- 20801456
TI  - High-performance liquid chromatography-off line mass spectrometry analysis of
      anthraquinones produced by Geosmithia lavendula.
AB  - Lilac coloured species of Geosmithia lavendula produce a mixture of
      polyhydroxylated anthraquinones under condition of submerged fermentation. Three
      pigments had been isolated and identified earlier as a 1,3,6,8
      tetrahydroxyanthraquinone (compound 7), rhodolamprometrin (1-acetyl 2,4,5,7
      tetrahydroxyanthraquinone; compound 5), and 1-acetyl 2,4,5,7,8
      penthahydroxyanthraquinone (compound 4). A new HPLC method was developed for the
      separation of three known and ten new anthraquinone pigments. In addition, five
      new pigments were determined by FTMS as coeluting impurities. The analyses were
      performed on a reversed phase column using gradient elution with a mobile phase
      system consisting of phosphate buffer (50 mM; pH=2.0) and acetonitrile. The
      structure evaluation was based namely on FTMS and UV-VIS spectrometry. The
      developed procedure was used for the determination of individual anthraquinones
      in fermentation broth of G. lavendula after 14 days of cultivation. The
      extractable amount and LOQ (both in MUg ml(-1)) for the two main pigments from G.
      lavendula are 50.02 and 2.15 for compound 4, and 63.77 and 2.75, for compound 5,
      respectively.

PMID- 20801457
TI  - Sustained attention and age predict inhibitory control during early childhood.
AB  - Executive functioning skills develop rapidly during early childhood. Recent
      research has focused on specifying this development, particularly predictors of
      executive functioning skills. Here we focus on sustained attention as a predictor
      of inhibitory control, one key executive functioning component. Although
      sustained attention and inhibitory control have been linked in older children and
      adults, these links have not been well specified during early childhood. The
      current study examined both parent-rated and laboratory measures of sustained
      attention as predictors of both parent-rated and laboratory measures of
      inhibitory control among 3- to 6-year-olds. As expected, children with higher
      sustained attention abilities exhibited greater inhibitory control. Moreover,
      inhibitory control increased across age. These findings reveal important details
      about the development of sustained attention and inhibitory control during early
      childhood.

PMID- 20801459
TI  - The triglyceride to high-density lipoprotein-cholesterol ratio in adolescence and
      subsequent weight gain predict nuclear magnetic resonance-measured lipoprotein
      subclasses in adulthood.
AB  - OBJECTIVE: To assess whether the fasting triglyceride-to-high-density lipoprotein
      (HDL)-cholesterol (TG/HDL) ratio in adolescence is predictive of a proatherogenic
      lipid profile in adulthood. STUDY DESIGN: A longitudinal follow-up of 770 Israeli
      adolescents 16 to 17 years of age who participated in the Jerusalem Lipid
      Research Clinic study and were reevaluated 13 years later. Lipoprotein particle
      size was assessed at the follow-up with proton nuclear magnetic resonance.
      RESULTS: The TG/HDL ratio measured in adolescence was strongly associated with
      low-density lipoprotein, very low-density lipoprotein (VLDL), and HDL mean
      particle size in young adulthood in both sexes, even after adjustment for
      baseline body mass index and body mass index change. The TG/HDL ratio measured in
      adolescence and subsequent weight gain independently predicted atherogenic small
      low-density lipoprotein and large VLDL particle concentrations (P < .001 in both
      sexes). Baseline TG/HDL and weight gain interacted to increase large VLDL
      concentration in men (P < .001). CONCLUSIONS: Adolescents with an elevated TG/HDL
      ratio are prone to express a proatherogenic lipid profile in adulthood. This
      profile is additionally worsened by weight gain.

PMID- 20801460
TI  - Physical activity and academics.

PMID- 20801461
TI  - Incomplete specialty referral among children in community health centers.
AB  - OBJECTIVE: To assess rates of incomplete specialty referral (referral not
      resulting in a specialist visit) and risk factors for incomplete referral in
      pediatric community health care centers. STUDY DESIGN: In this cross-sectional
      study, we used referral records and electronic health records to calculate rate
      of incomplete referral in 577 children referred from two health care centers in
      underserved communities to any of 19 pediatric specialties at an affiliated
      tertiary care center, over 7 months in 2008-2009. We used logistic regression to
      test the association of incomplete referral with child/family sociodemographic
      and health care system factors. RESULTS: Of the children, 30.2% had an incomplete
      referral. Incomplete referral rates were similar at the two health care centers,
      but varied from 10% to 73% according to specialty clinic type. In multivariate
      analysis, sociodemographic factors of older child age, public insurance status,
      and no chronic health conditions correlated with incomplete referral, as did
      health care system factors of surgical specialty clinic type, low patient volume,
      longer wait for visit, and appointment rescheduling. CONCLUSION: Almost one-third
      of children referred to specialists were unable to complete the referral in a
      timely manner. To improve specialty access, health care organizations and
      policymakers should target support to families with high-risk children and
      remediate problematic health care system features.

PMID- 20801462
TI  - Normative cerebrospinal fluid profiles in febrile infants.
AB  - OBJECTIVE: To describe the cerebrospinal fluid (CSF) profiles of febrile infants
      aged 1 to 90 days with negative bacterial culture test results and negative
      results for enteroviruses with polymerase chain reaction. STUDY DESIGN:
      Statistical analysis of a retrospective cohort. RESULTS: CSF profiles from 823
      infants with negative test results for infection were analyzed. For 677 infants
      with atraumatic lumbar punctures (red blood cell [RBC] count < 1000/mm(3)), the
      mean and median CSF white blood cell (WBC) counts were 4.3/mm(3) and 3.0/mm(3),
      respectively, with a range from 0 to 12/mm(3). Mean CSF WBC counts (6.1/mm(3)
      versus 3.1/mm(3) and 3.0/mm(3)) and protein levels (75.4 mg/dL versus 58.9 mg/dL
      and 39.2 mg/dL) were higher in the first month compared with months 2 and 3,
      respectively (P < .001 for all). CSF glucose levels were lower in the first month
      compared with month 3 (45.3 mg/dL versus 48.0 mg/dL and 57.7 mg/dL; P < .001).
      Increasing RBC counts were statistically associated with increasing WBC counts (P
      < .001). However, the contribution of RBC < 10,000/mm(3) was small, and the
      reference range for WBC in uninfected infants with traumatic lumbar punctures was
      0 to 16/mm(3). CONCLUSION: CSF WBC counts in febrile infants without evidence of
      bacterial or enteroviral infection, even in those with traumatic lumbar puncture,
      are lower than reported in pediatric references.

PMID- 20801463
TI  - Psychopathology in offspring from families of alcohol dependent female probands:
      a prospective study.
AB  - BACKGROUND: Despite the importance of understanding the long-term outcome for
      children of alcohol dependent (AD) women, the available literature is largely
      based on offspring of AD fathers and few have utilized prospective designs that
      include child, adolescent and young adult assessments. Multiplex AD families in
      which multiple cases of AD are present provide an ideal setting for understanding
      developmental variants of the adult phenotype. METHOD: Offspring from multiplex
      AD families identified through the mother or control families were evaluated
      multiple times during childhood and followed to young adulthood. Familial risk
      status and the presence of specific child/adolescent disorders were used as
      predictors of substance use disorder outcome by young adulthood. RESULTS:
      Offspring who were members of maternal multiplex families had elevated rates of
      child and young adulthood disorders. High risk offspring of alcohol dependent
      women were at increased risk for externalizing (Conduct Disorder and ADHD) and
      internalizing disorders (Major Depressive Disorder (MDD) and Anxiety Disorders).
      By young adulthood, offspring from these multiplex families had significantly
      greater odds of developing alcohol abuse or dependence (odds ratio [OR] = 3.63
      [CI 1.36-9.64]) and drug abuse or dependence (OR = 4.23 [CI 1.73-10.32]). The
      prospective design of the study revealed that specific childhood disorders
      (Conduct Disorder, ADHD, MDD) increased the odds of subsequent development of
      substance use disorder (SUD). CONCLUSIONS: Multiplex familial risk for alcohol
      dependence is a significant predictor of substance use disorders by young
      adulthood. Familial risk and an earlier childhood disorder may set the stage for
      later development of SUD.

PMID- 20801464
TI  - Comparing venlafaxine extended release and fluoxetine for preventing the
      recurrence of major depression: results from the PREVENT study.
AB  - This secondary analysis from the Prevention of Recurrent Episodes of Depression
      with Venlafaxine Extended Release (ER) for Two Years (PREVENT) study compared the
      efficacy of venlafaxine ER and fluoxetine for the prevention of recurrence in
      patients with a history of recurrent major depressive disorder (MDD). Patients
      received double-blind treatment with venlafaxine ER (75-300 mg/d) or fluoxetine
      (20-60 mg/d) for 10 weeks (acute phase). Responders (17-item Hamilton Rating
      Scale for Depression [HAM-D(17)] score <= 12 and >= 50% reduction from baseline)
      continued on the same treatment during the 6-month continuation phase. At the
      start of the first and second 12-month maintenance phases, venlafaxine ER
      responders were randomly assigned to receive venlafaxine ER or placebo, whereas
      patients receiving fluoxetine continued to receive fluoxetine throughout both
      maintenance phases. The primary outcome was time to recurrence (HAM-D(17) > 12,
      reduction in HAM-D(17) score <= 50% from acute baseline, and meeting DSM-IV
      criteria for a diagnosis of MDD), which was assessed using Kaplan-Meier
      estimates. Using the primary definition of recurrence, the estimated probability
      of not experiencing a recurrence was 71.9% for venlafaxine ER (n = 160) and 55.8%
      for fluoxetine (n = 99) across 24 months of maintenance treatment. For this
      primary analysis, the overall effect of venlafaxine ER treatment was not
      statistically significant (p = 0.399) compared with fluoxetine; however, a
      significant treatment-by-time interaction was observed (p = 0.034). No
      significant between-group differences were observed with any of the secondary
      efficacy variables. Venlafaxine ER and fluoxetine were similarly well tolerated
      across 2 years of maintenance-phase therapy.

PMID- 20801465
TI  - Cytotoxic triterpenoid saponins acylated with monoterpenic acids from fruits of
      Gleditsia caspica Desf.
AB  - Four bisdesmosidic triterpenoid saponins named caspicaosides A-D, were isolated
      from the fruits of Gleditsia caspica Desf. Their structures were determined by
      NMR spectroscopy including HOHAHA, 1H-1H COSY, ROE, HMQC, HMBC experiments and
      HRFAB-MS as well as acid hydrolysis. The four 3,28-O-bisdesmosidic triterpenoid
      saponins comprised echinocystic acid as the aglycone and common oligosaccharide
      moieties at C3 and C28. The saccharide moiety at C-3 was identified as beta-D
      xylopyranosyl-(1->2)-alpha-L-arabinopyranosyl-(1->6)-beta-D-glucopyranosyl while
      that at C-28 was determined as beta-D-xylopyranosyl-(1->3)-beta-d-xylopyranosyl
      (1->4)-alpha-L-rhamnopyranosyl-(1->2)-[alpha-L-rhamnopyranosyl-(1->6)-]beta-D
      glucopyranosyl. The pentasaccharide moiety linked to C-28 was acylated with
      monoterpenic acid and or monoterpene-arabinoside moieties at C-2 or C-2 and C-3
      of the terminal rhamnose unit. The isolated saponins were assayed for their in
      vitro cytotoxicities against the three human tumor cell lines HepG2, A549 and
      HT29 using MTT method. The results showed that caspicaosides B and C bearing two
      and three monoterpene units, respectively, exhibited significant cytotoxic
      activities against the used cell lines with IC50 values 1.5-6.5 MUM.
      Caspicaosides A and D with one monoterpene unit exhibited significant cytotoxic
      activities on HepG2 cell line with IC50 values equal to 4.5 and 5.4 MUM,
      respectively, and IC50 values > 10 MUM against the other two cell lines. The
      number of monoterpene units seems to play a main role in determining the
      activity.

PMID- 20801466
TI  - Inhibitor and substrate activities of sesquiterpene olefins toward +-delta
      cadinene-8-hydroxylase, a cytochrome P450 monooxygenase (CYP706B1).
AB  - Several lines of evidence indicate that (+)-delta-cadinene-8-hydroxylase
      (CYP706B1) plays an important role in biosynthesis of gossypol in Gossypium
      arboreum L. (Luo et al., 2001; Wang et al., 2003). The catalytically active
      enzyme has been expressed in yeast microsomes. Some microsomal preparations
      conjugated the hydroxylated (+)-delta-cadinene to a moiety that has not yet been
      identified. However, when microsomes were treated with n-octyl-beta-d-glucoside
      (OG), a non-ionic detergent, (+)-delta-cadinene was reproducibly converted to the
      free alcohol, 8-hydroxy-(+)-delta-cadinene. OG had little effect on K(m) and
      slightly stimulated apparent V(max). Enzymic activity was more than 10-fold more
      sensitive to inhibition by the N-substituted imidazole clotrimazole than to
      miconazole. Sesquiterpene olefins (-)-delta-cadinene, (-)-alpha-cubebene, (-)
      alpha-muurolene, alpha-humulene, and a mixture of (-)- and (+)-alpha-copaene were
      inhibitory to hydroxylation of (+)-delta-cadinene. In addition, (-)-alpha
      cubebene, (-)-alpha-muurolene, alpha-humulene, and, to a smaller extent, (-)
      delta-cadinene served as alternative substrates for (+)-delta-cadinene-8
      hydroxylase and were converted to mono-hydroxylated products. Of the five olefins
      tested, alpha-humulene and alpha-copaene are found in lysigenous glands of cotton
      (Elzen et al., 1985), which are also the site of gossypol accumulation (Bell et
      al., 1978; Mace et al., 1976) and the probable site of its biosynthesis.

PMID- 20801467
TI  - Peripheral white blood cell counts throughout pregnancy in non-aborting Neospora
      caninum-seronegative and seropositive high-producing dairy cows in a Holstein
      Friesian herd.
AB  - Pregnancy is characterized by transient changes in the maternal immune system,
      also evident at peripheral level. The present study analyzes the kinetics and
      possible factors affecting peripheral white blood cell populations throughout
      pregnancy in a herd of high-producing dairy cows chronically infected or not with
      Neospora caninum. We examined 54 pregnant parous cows: 29 Neospora-seronegative
      and 25 Neospora-seropositive cows. Blood samples were collected on Days 90, 120,
      150, 180 and 210 of gestation. General Linear Model (GLM) repeated measures
      analysis of variance showed that the interaction Neospora-seropositivity * parity
      significantly affected total leukocyte, neutrophil and monocyte counts with lower
      levels of total leukocytes, lower neutrophil and higher monocyte counts recorded
      in primiparous Neospora-seropositive cows. In addition, N. caninum-seropositive
      cows had significantly increased monocyte counts on Day 180 of gestation compared
      to seronegative ones. Other factors significantly associated with changes in
      total and/or differential leukocyte profiles were period of pregnancy, season,
      twin pregnancy and milk production. In conclusion, a parity-associated effect of
      chronic N. caninum infection was observed on peripheral blood cell profiles in
      dairy cattle during gestation.

PMID- 20801468
TI  - [Bifid mandibular condyle: position of the supernumerary condyle].
AB  - INTRODUCTION: Bifid condyles are uncommon and include post-traumatic aberrant
      reorganization of the temporomandibular joint (TMJ) and congenital forms. CASE
      REPORT: We report two cases of unilateral bifid condyles, responsible for
      functional dysfunction of the TMJ. The first case, probably of congenital origin,
      was oriented frontally. The second case, oriented in the sagittal plane, was
      probably post-traumatic. Functional treatment was used for both patients.
      DISCUSSION: Bifid condyles is asymptomatic in most cases. Their most frequent
      clinical consequence is TMJ pain. Surgical treatment is rarely indicated.
      Determining the congenital or post-traumatic origin of bifid condyles is often
      difficult. The orientation of the supernumerary condyle head could help for the
      etiological diagnosis.

PMID- 20801469
TI  - [Parkinson's diseases: power of search].

PMID- 20801470
TI  - [REM sleep behavior disorder: an overt access to motor and cognitive control
      during sleep].
AB  - Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by
      violent, or potentially violent, movements during REM sleep, corresponding to
      enacted dreams. During sleep monitoring, there is a partial or total loss of the
      normal muscle atonia during REM sleep. REM sleep behavior disorder predominantly
      affects elderly subjects without any other disease (idiopathic RBD, a precursor
      of Parkinson disease and Lewy body dementia) or suffering from various
      neurological and neurodegenerative diseases, mainly synucleinopathies. In
      addition to being a treatable cause of nocturnal injury of the patients or their
      bed-partners, RBD is a fantastic window into motor and cognitive control during
      REM sleep. Notably, parkinsonism transiently disappears during RBD. The patient's
      voice is louder and better articulated than when awake, and movements are rapid
      (but jerky) suggesting that the deleterious message from the basal ganglia to the
      primary motor cortex is reduced or bypassed. As we observed culturally-acquired
      behaviors, retired patients practicing their former work with mastered gestures,
      as well as sentences pronounced with appropriate prosody, gesturing, fluency, and
      syntax during the RBD, we suggest that these behaviors are generated by the same
      cortical areas as during wakefulness. This model also enables the demonstration
      that REM during REM sleep are coded in the same direction as the arm and hand
      movements, as if the dreamer were scanning the dream images. This online access
      to the motor and verbal dream scenario (through the video and audio monitoring),
      and the physiological measures (via the EEG, eye movements, muscle tone,
      respiration, heart rate), together with the offline access to the mental content
      (dream report after the awakening) constitute a triangulation for validating new
      hypotheses about REM sleep and dreams.

PMID- 20801471
TI  - Serodiagnostic reliability of single-step enriched low-molecular weight proteins
      of Taenia solium metacestode of American and Asian isolates.
AB  - The low-molecular weight proteins (LMWPs) of Taenia solium metacestode (TsM)
      constituted pertinent serodiagnostic antigens for cysticercosis. We established a
      novel single-step purification of the LMWPs from TsM cyst fluid (CF). When the CF
      was precipitated with trichloroacetic acid/acetone mixture at the final
      concentrations of 5 and 50%, most LMWPs (ranging 7-38kDa) remained in the
      supernatant fraction. Sodium dodecyl sulfate polyacrylamide gel electrophoresis
      (SDS-PAGE) and immunoblot analyses revealed that the LMWPs consisted mainly with
      the previously reported subunit proteins of the 120- and 150-kDa antigen
      complexes. Serum samples from neurocysticercosis (NC) and other helminthic
      infections, as well as those from healthy controls were tested by both
      immunoblotting and micro-ELISA. In 135 cases of active stage NC patients, 132
      cases (97.7%) showed positive reactions. Serum samples from other helminthic
      diseases (n=125) and healthy controls (n=100) exhibited no positive reactions
      except for cystic echinococcosis, of which 12% (3/25 cases) exhibited low levels
      of cross-reactivity. The LMWPs from different geographical regions (Korea and
      Mexico) showed diagnostic sensitivity and specificity of 97.7% and 98.7% against
      active stage NC. Our single-step separation method for the LMWPs provided
      excellent performance with easy applicability and high reproducibility, which has
      a great benefit for preparation of potent antigen in endemic areas.

PMID- 20801472
TI  - Reply to comment: left upper quadrant abdominal pain in malaria: suspect
      pathological splenic rupture first.

PMID- 20801473
TI  - Long-term clinical evaluation of asymptomatic subjects positive for circulating
      Taenia solium antigens.
AB  - Although presence of cysticercal antigens in serum is presumed to indicate active
      cysticercosis not all positive persons are symptomatic. The significance of a
      positive antigen test in asymptomatic individuals, in predicting development of
      symptomatic cysticercosis on long-term follow up, is unknown. Forty two of 48
      persons from Vellore district, India who were positive for circulating serum
      cysticercal antigens were followed up for four to five years. None of them
      developed clinical evidence of neurocysticercosis or subcutaneous cysts. We
      conclude that asymptomatic individuals with circulating cysticercal antigens have
      a low risk of developing symptomatic cysticercosis within four to five years.

PMID- 20801474
TI  - Trastuzumab-binding peptide display by Tobacco mosaic virus.
AB  - Human epidermal growth factor receptor-2 (HER2/neu) is a target for the humanized
      monoclonal antibody trastuzumab. Recently, trastuzumab-binding peptides (TBP) of
      HER2/neu that inhibit proliferation of breast cancer cells were identified. We
      have now studied conditions of efficient assembly in vivo of Tobacco mosaic virus
      (TMV)-based particles displaying TBP on its surface. The system is based on an
      Agrobacterium-mediated co-delivery of binary vectors encoding TMV RNA and coat
      protein (CP) with TBP in its C-terminal extension into plant leaves. We show how
      the fusion of amino acid substituted TBP (sTBP) to CP via a flexible peptide
      linker can improve the manufacturability of recombinant TMV (rTMV). We also
      reveal that rTMV particles with exposed sTBP retained trastuzumab-binding
      capacity but lost an anti-HER2/neu immunogenic scaffold function. Mouse
      antibodies against rTMV did not recognize HER2/neu on surface of human SK-BR-3
      cells.

PMID- 20801475
TI  - Improvement of metal adsorption onto chitosan/Sargassum sp. composite sorbent by
      an innovative ion-imprint technology.
AB  - Technology for immobilization of biomass has attracted a great interest due to
      the high sorption capacity of biomass for sequestration of toxic metals from
      industrial effluents. However, the currently practiced immobilization methods
      normally reduce the metal sorption capacities. In this study, an innovative ion
      imprint technology was developed to overcome the drawback. Copper ion was first
      imprinted onto the functional groups of chitosan that formed a pellet-typed
      sorbent through the granulation with Sargassum sp.; the imprinted copper ion was
      chemically detached from the sorbent, leading to the formation of a novel copper
      ion-imprinted chitosan/Sargassum sp. (CICS) composite adsorbent. The copper
      sorption on CICS was found to be highly pH-dependent and the maximum uptake
      capacity was achieved at pH 4.7-5.5. The adsorption isotherm study showed the
      maximum sorption capacity of CICS of 1.08 mmol/g, much higher than the non
      imprinted chitosan/Sargassum sp. sorbent (NICS) (0.49 mmol/g). The used sorbent
      was reusable after being regenerated through desorption. The FTIR and XPS studies
      revealed that the greater sorption of heavy metal was attributed to the large
      number of primary amine groups available on the surfaces of the ion-imprinted
      chitosan and the abundant carboxyl groups on Sargassum sp. Finally, an
      intraparticle surface diffusion controlled model well described the sorption
      history of the sorbents.

PMID- 20801476
TI  - Combined anaerobic and aerobic digestion for increased solids reduction and
      nitrogen removal.
AB  - A unique sludge digestion system consisting of anaerobic digestion followed by
      aerobic digestion and then a recycle step where thickened sludge from the aerobic
      digester was recirculated back to the anaerobic unit was studied to determine the
      impact on volatile solids (VS) reduction and nitrogen removal. It was found that
      the combined anaerobic/aerobic/anaerobic (ANA/AER/ANA) system provided 70% VS
      reduction compared to 50% for conventional mesophilic anaerobic digestion with a
      20 day SRT and 62% for combined anaerobic/aerobic (ANA/AER) digestion with a 15
      day anaerobic and a 5 day aerobic SRT. Total Kjeldahl nitrogen (TKN) removal for
      the ANA/AER/ANA system was 70% for sludge wasted from the aerobic unit and 43.7%
      when wasted from the anaerobic unit. TKN removal was 64.5% for the ANA/AER
      system.

PMID- 20801477
TI  - Nitritation performance in membrane-aerated biofilm reactors differs from
      conventional biofilm systems.
AB  - Nitrogen removal via nitrite has gained increasing attention in recent years due
      to its potential cost savings. Membrane-aerated biofilm reactors (MABRs) are one
      potential technology suitable to achieve nitritation. In this study we compared
      lab scale MABRs with conventional biofilm reactors to evaluate the influence of
      environmental conditions and operational parameters on nitritation performance.
      The oxygen mass transfer rate is postulated as a crucial parameter to control
      nitritation in the MABR: Clean water measurements showed significant
      underestimation of the total oxygen mass transfer, however, accurate
      determination of the oxygen mass transfer coefficient (k(m)) of the system could
      be achieved by adjusting the liquid-phase mass transfer resistance in the
      constructed model. Batch experiments at different initial ammonium concentrations
      revealed that the conventional biofilm geometry was superior for nitritation
      compared to MABRs. These differences were reflected well in estimates of the
      oxygen affinity constants of the key microbial players, AOB and NOB (K(O,AOB) <
      K(O,NOB) (in both systems) and K(O,NOB) values smaller in the MABR vs. the
      conventional biofilm system). It also appeared that - in addition to oxygen
      limitation - the absolute and relative substrate concentrations in the biofilm
      (esp. of oxygen) are very important for successful nitritation. Initial biomass
      composition, furthermore, impacted reactor performance in the MABR systems
      indicating the need for appropriate inoculum choice.

PMID- 20801478
TI  - Performance of high-loaded ANAMMOX UASB reactors containing granular sludge.
AB  - The performance of high-loaded anaerobic ammonium oxidizing (ANAMMOX) upflow
      anaerobic sludge bed (UASB) reactors was investigated. Two ANAMMOX reactors (R1
      with and R2 without effluent recycling, respectively) were fed with relatively
      low nitrite concentration of 240 mg-N L(-1) with subsequent progressive increase
      in the nitrogen loading rate (NLR) by shortening the hydraulic retention time
      (HRT) till the end of the experiment. A super high-rate performance with nitrogen
      removal rate (NRR) of 74.3-76.7 kg-N m(-3) day(-1) was accomplished in the lab
      scale ANAMMOX UASB reactors, which was 3 times of the highest reported value. The
      biomass concentrations in the reactors were as high as 42.0-57.7 g-VSS L(-1) with
      the specific ANAMMOX activity (SAA) approaching to 5.6 kg-N kg-VSS(-1) day(-1).
      The high SAA and high biomass concentration were regarded as the key factors for
      the super high-rate performance. ANAMMOX granules were observed in the reactors
      with settling velocities of 73-88 m h(-1). The ANAMMOX granules were found to
      contain a plenty of extracellular polymers (ECPs) such as 71.8-112.1 mg g-VSS(-1)
      of polysaccharides (PS) and 164.4-298.2 mg g-VSS(-1) of proteins (PN). High
      content of hemachrome (6.8-10.3 MUmol g-VSS(-1)) was detected in the ANAMMOX
      granules, which is supposed to be attributed to their unique carmine color.

PMID- 20801479
TI  - Photochemical fate of atorvastatin (lipitor) in simulated natural waters.
AB  - Cholesterol-lowering statin drugs are among the most frequently prescribed for
      reducing human blood cholesterol and they have been detected as contaminants in
      natural waters. In this study the photochemical behavior of atorvastatin
      (lipitor) was investigated at two different concentrations of 35.8 MUM (20 mg L(
      1)) and 35.8 nM (20 MUg L(-1)) using a solar simulator and a UV reactor.
      Photochemical fate in natural waters can be described in most cases by the sum of
      the loss due to hydrolysis, direct photolysis, and, reaction with hydroxyl
      radical (*OH), singlet oxygen ((1)O(2)) (or O(2) ((1)D)), and excited state
      dissolved organic matter (DOM). The absolute bimolecular reaction rate constant
      with OH was measured, using pulsed radiolysis, (1.19 +/- 0.04) * 10(10) M(-1) s(
      1). The reaction rate constant of (1)O(2) was determined to be (3.1 +/- 0.2) *
      10(8) M(-1) s(-1). Under the experimental conditions used, at high atorvastatin
      concentration (35.8 MUM) the contribution of singlet oxygen ((1)O(2)) to the
      photodegradation of atorvastatin in natural waters was higher than that of
      hydroxyl radical, and accounted for up to 23% of the loss in aqueous solutions.
      Whereas, at a concentration of 35.8 nM, (1)O(2) (and *OH) both played a minor
      role in the removal of this compound. Lastly, it also appears that atorvastatin
      reacts with (3)DOM* contributing to its loss in simulated natural waters.

PMID- 20801480
TI  - Biological treatment of propanil and 3,4-dichloroaniline: kinetic and
      microbiological characterisation.
AB  - Propanil (3,4-dichloropropionanilide) is a widely used herbicide, applied
      worldwide in rice paddies. Propanil is primarily transformed in nature to 3,4
      dichloroaniline (DCA), which is more slowly biodegradable. Both compounds have
      adverse health and ecotoxicity effects. This work investigated the microbial
      ecology and kinetics of propanil-degrading enrichments obtained from soil in a
      sequencing batch reactor (SBR) operated with different feeding strategies, aiming
      at the enhanced biological removal of propanil and DCA from contaminated waters.
      During SBR operation with a dump feeding strategy, a high propanil concentration
      led to DCA accumulation, which was only fully degraded after 5 days, likely due
      to DCA inhibition. For this reason, the operational mode was changed to fed-batch
      operation with lower initial propanil concentrations, which resulted in faster
      propanil and DCA biodegradation. Thus a fed-batch operation seems more
      appropriate for the acclimatisation of an effective propanil- and DCA-degrading
      population. The changes in performance were accompanied by a shift in the
      microbial population structure, as determined by DGGE of the 16S rRNA gene,
      particularly after a feed of DCA as the sole carbon source. Isolates obtained
      from the acclimatised population included members of the genera Enterococcus and
      Rhodococcus, as well as Brevundimonas, which displayed >90% propanil
      biodegradation efficiency.

PMID- 20801481
TI  - Diuron biotransformation and its effects on biofilm bacterial community
      structure.
AB  - The effect of realistic environmental contamination of diuron on natural
      epilithic biofilms dwelling bacterial communities and their transformation
      capacities were investigated by using microcosm experiments. Cobbles carrying
      biofilms from two sites ("Pau" and "Lacq") located in areas of contrasting
      pesticide use (urban and agricultural) on the Gave de Pau river (South-West
      France) were analysed. The water of the upstream site, Pau, was characterised by
      fewer pesticides than the water of Lacq, whereas concentrations were higher at
      Pau. The sampled cobbles were exposed to diuron (10 MUg L(-1)) in microcosms.
      After 3 weeks of exposure, pesticides were analysed and bacterial community
      structures were assessed with terminal-restriction fragment length polymorphism
      (T-RFLP). Diuron was biotransformed during contact with biofilms, revealing that
      these communities contribute to the production of DCPMU (1-(3,4-dichlorophenyl)-3
      methylurea) and DCPU metabolites (1-(3,4-dichlorophenyl) urea) in the river
      ecosystems. Bacterial communities from the most contaminated site appeared to be
      more resistant to diuron exposure. Correlation analyses combining chemical data
      with molecular fingerprinting showed that past in situ exposure drove the
      response of the bacterial communities.

PMID- 20801482
TI  - Degradation of trinitroglycerin (TNG) using zero-valent iron
      nanoparticles/nanosilica SBA-15 composite (ZVINs/SBA-15).
AB  - Trinitroglycerin (TNG) is an industrial chemical mostly known for its clinical
      use in treating angina and manufacturing dynamite. The wide manufacture and
      application of TNG has led to contamination of vast areas of soil and water. The
      present study describes degradation of TNG with zero-valent iron nanoparticles
      (ZVINs) in water either present alone or stabilized on nanostructured silica SBA
      15 (Santa Barbara Amorphous No. 15). The BET surface areas of ZVINs/SBA-15 (275.1
      m2 g(-1)), as determined by nitrogen adsorption-desorption isotherms, was much
      larger than the non-stabilized ZVINs (82.0 m2 g(-1)). X-ray diffraction (XRD)
      showed that iron in both ZVINs and ZVINs/SBA-15 was present mostly in the alpha
      Fe0 crystalline form considered responsible for TNG degradation. Transmission
      Electron Microscopy (TEM) showed that iron nanoparticles were well dispersed on
      the surface of the nanosilica support. Both ZVINs and ZVINs/SBA-15 degraded TNG
      (100%) in water to eventually produce glycerol and ammonium. The reaction
      followed pseudo-first-order kinetics and was faster with ZVINs/SBA-15 (k1 0.83
      min(-1)) than with ZVINs (k1 0.228 min(-1)). The corresponding surface-area
      normalized rate constants, knorm, were 0.36 and 0.33 L h(-1) m(-2) for ZVINs/SBA
      15 and ZVINs, respectively. The ZVINs/SBA-15 retained its original degradation
      efficiency of TNG after repeatedly reacting with fresh nitrate ester for five
      successive cycles. The rapid and efficient transformation of TNG with ZVINs/SBA
      15, combined with excellent sustained reactivity, makes the nanometal an ideal
      choice for the clean up of water contaminated with TNG.

PMID- 20801483
TI  - Electroanalytical studies of sulfentrazone in protic medium, its degradation by
      the electro-Fenton process, and toxicity assessment using ss-DNA.
AB  - Sulfentrazone is an herbicide used as a pre-plant incorporated or pre-emergence
      treatment. The electrochemical oxidation of sulfentrazone was studied, by cyclic,
      differential and square-wave voltammetry on unmodified and on glassy carbon
      nanotube-modified electrodes, and by controlled-potential coulometry and
      electrolysis. The voltammograms of sulfentrazone showed a main irreversible
      diffusion-controlled pH-dependent oxidation peak. The in situ DNA-damaging
      capacity of sulfentrazone was also investigated, employing double stranded ds-DNA
      modified glassy carbon electrode, without evidence of interaction. On the other
      hand, in a solution of sulfentrazone and single stranded ss-DNA, the oxidation
      signals of the respective bases decreased concentration-dependently, indicating
      binding of sulfentrazone to guanine and adenine. The electro-Fenton method was
      employed to promote decontamination by eliminating the herbicide, resulting in
      almost 60% of mineralization.

PMID- 20801484
TI  - Complexation of arsenite with dissolved organic matter: conditional distribution
      coefficients and apparent stability constants.
AB  - The complexation of arsenic (As) with dissolved organic matter (DOM), although
      playing an important role in regulating As mobility and transformation, is poorly
      characterized, as evidenced by scarce reporting of fundamental parameters of As
      DOM complexes. The complexation of arsenite (AsIII) with Aldrich humic acid (HA)
      at different pHs was characterized using a recently developed analytical
      technique to measure both free and DOM-bound As. Conditional distribution
      coefficient (KD), describing capacity of DOM in binding AsIII from the mass
      perspective, and apparent stability constant (Ks), describing stability of
      resulting AsIII-DOM complexes, were calculated to characterize AsIII-DOM
      complexation. LogKD of AsIII ranged from 3.7 to 2.2 (decreasing with increase of
      As/DOM ratio) at pH 5.2, from 3.6 to 2.6 at pH 7, and from 4.3 to 3.2 at pH=9.3,
      respectively. Two-site ligand binding models can capture the heterogeneity of
      binding sites and be used to calculate Ks by classifying the binding sites into
      strong (S1) and weak (S2) groups. LogKs for S1 sites are 7.0, 6.5, and 5.9 for pH
      5.2, 7, and 9.3, respectively, which are approximately 1-2 orders of magnitude
      higher than for weak S2 sites. The results suggest that AsIII complexation with
      DOM increases with pH, as evidenced by significant spikes in concentrations of
      DOM-bound AsIII and in KD values at pH 9.3. In contrary to KD, logKs decreased
      with pH, in particular for S1 sites, probably due to the presence of negatively
      charged H2AsO3- and the involvement of metal-bridged AsIII-DOM complexation at pH
      9.3.

PMID- 20801485
TI  - Hydrolysis of fluorotelomer compounds leading to fluorotelomer alcohol production
      during solvent extractions of soils.
AB  - The experimental approaches used in assessing the biodegradability of
      fluorotelomer-based surfactants and polymers have been under increasing scrutiny.
      These substances consist of an aliphatic or aromatic backbone linked to
      perfluoroethyl moieties by ester, ether or urethane linkages. These linkages when
      broken yield fluorotelomer alcohols (FTOHs), which are known to biotransform to a
      suite of polyfluorinated metabolites including perfluorinated carboxylic acids.
      Quantifying FTOH levels with minimal experimental artifacts is imperative in
      properly assessing the biotransformation potential and half-lives of
      fluorotelomer-based materials. We examined the potential for solvent-enhanced
      ester hydrolysis of fluorotelomer compounds with different hydrocarbon backbones
      including a monoester stearate (FTS), a citrate tri-ester (TBC), an acrylate
      (FTA), and a 2,4-toluenediamine urethane (FTU) in acetonitrile, methyl-t-butyl
      ether (MTBE), and ethyl acetate with live, autoclaved, 60Co-gamma-irradiated, and
      heat-treated (400 degrees C) soils. Substantial hydrolysis only occurred with FTS
      in live and gamma-irradiated soils for which microbial enzymes are expected to be
      active, but not in autoclaved soils where enzymes are deactivated. Acetonitrile
      and methanol (solvents with higher dielectric constants) enhanced hydrolysis by
      an order of magnitude compared to less polar solvents such as MTBE and ethyl
      acetate. For example, in a 24-h extraction with acetonitrile of FTS-amended soil,
      >5wt.% FTOH was produced compared to <0.04wt.% in either ethyl acetate or MTBE.
      FTA hydrolysis was <0.7 wt.% after a 15-h extraction period and was not solvent
      dependent. No statistically significant solvent-enhanced hydrolysis was observed
      for TBC, FTA or FTU.

PMID- 20801486
TI  - Odor detection thresholds of naphthenic acids from commercial sources and oil
      sands process-affected water.
AB  - Naphthenic acids (NAs) occur naturally in various petroleums and in oil sands
      tailings waters and have been implicated as potential fish tainting compounds. In
      this study, trained sensory panels and the general population from a university
      were used to determine the odor detection thresholds of two commercial NAs
      preparations (Acros and Merichem) and of NAs extracted from an oil sands
      experimental reclamation pond (Pond 9). Using the three-alternative forced choice
      method, a concentration series of NAs were presented to the sensory panels in
      phosphate buffer (pH 8) and in steamed fish (Sander vitreus). In buffer, the odor
      detection thresholds of Acros, Merichem and Pond 9 NAs, as evaluated by the
      trained panelists, were 1.5, 0.04, and 1.0 mg L(-1), respectively. Only the
      detection threshold for the Merichem NAs was significantly different (p<0.01)
      than the other two sources. Based on the general population assessments, all
      three odor detection thresholds were significantly different from one another;
      4.8, 0.2, and 2.5 mg L(-1) for Acros, Merichem, and Pond 9 NAs, respectively
      (p<0.01). The odor detection thresholds of Merichem and Pond 9 NAs in steamed
      fish were 0.6 and 12 mg kg(-1), respectively and were significantly different
      from each other (p<0.01). The detection threshold of Acros NAs was estimated to
      be >21 mg kg(-1). For the steamed fish evaluations, the odor descriptors of all
      three of the NAs preparations was given as chemical in nature (Acros: oil,
      plastic; Merichem: gasoline; Pond 9: gasoline, tar). Exposure of live rainbow
      trout to a non-lethal concentration of Merichem NAs (3 mg L(-1) for 10 d)
      imparted an odor to the fish flesh. Analyses of the three NAs preparations by gas
      chromatography-mass spectrometry showed that each had a unique distribution of
      acids. We conclude that the source of the NAs is important when interpreting odor
      threshold data and that the two commercial preparations of NAs that were tested
      do not represent oil sands waters' tainting potential.

PMID- 20801487
TI  - Analysis of llicit and illicit drugs in waste, surface and lake water samples
      using large volume direct injection high performance liquid chromatography-
      electrospray tandem mass spectrometry (HPLC-MS/MS).
AB  - Llicit and illicit drugs represent a recent group of emerging contaminants and
      have been found in the aquatic environment. A HPLC-MS/MS method was developed
      using direct injection (DI) of larger volumes and a polar endcapped reversed
      phase (RP) column to measure drug components in water samples belonging to the
      cocaine group, opiates, amphetamine-like stimulants and metabolites thereof.
      After validation, including sensitivity, linearity, recovery, precision and
      matrix effect studies, most drugs could be detected with limits of quantitation
      (LOQ) of 20 ng L(-1) in wastewater (WW) and 0.2 ng L(-1) in surface water. The
      major substances found in influents and effluents were cocaine (COC),
      benzoylecgonine (BE), morphine (MO), methadone (MD) and its main metabolite 2
      ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) with concentrations up to
      2 MUg L(-1), followed by codeine (COD) and the amphetamines which ranged between
      20 and 400 ng L(-1). Except for MO, COD and EDDP levels were generally lower in
      the effluents. River and lake water contained trace amounts of mainly BE, MD and
      EDDP from the high pg L(-1) to the low ng L(-1) level. Monitoring COC and BE
      levels over 11 consecutive days in influents and effluents suggests a consumption
      preference on week-end days. Finally, measuring an influent after a major music
      event revealed that sewage treatment plants (STPs) are exposed, for a limited
      period of time, to high concentration peaks of COC and BE as well as amphetamine
      like stimulants such as ecstasy (MDMA).

PMID- 20801488
TI  - Comprehensive keratin profiling reveals different histopathogenesis of
      keratocystic odontogenic tumor and orthokeratinized odontogenic cyst.
AB  - Keratocystic odontogenic tumor is a cystic lesion that behaves more aggressively
      than other jaw cysts. One of its characteristic histologic features is a
      parakeratinized uniform layer of lining epithelium. A jaw cyst lined with
      orthokeratinized epithelium is called an orthokeratinized odontogenic cyst. These
      keratinized jaw cysts are thought to be separate entities, although their
      histopathogenesis has not been fully assessed. To better understand these
      lesions, we performed comprehensive immunohistochemical profiling of the keratin
      expression of each. Orthokeratinized odontogenic cysts expressed keratin 1,
      keratin 2, keratin 10, and loricrin, suggesting differentiation toward normal
      epidermis. Keratocystic odontogenic tumors expressed keratin 4, keratin 13,
      keratin 17, and keratin 19, which is a unique expression pattern reminiscent of a
      mucosal squamous epithelium and an epithelial appendage. In neonatal rat tooth
      germ, cells strongly positive for keratin 17 and keratin 19 were observed,
      specifically in the dental lamina, implying the origin of keratocystic
      odontogenic tumor. GLI2, a downstream effector of hedgehog signaling, was
      significantly expressed in keratocystic odontogenic tumor and basal cell
      carcinoma, accompanied with robust expression of keratin 17, mammalian target of
      rapamycin, and BCL2. The expression of these GLI2- or keratin 17-related factors
      was not significantly observed in orthokeratinized odontogenic cysts. These
      findings provide evidence to support the viewpoint that keratocystic odontogenic
      tumor and orthokeratinized odontogenic cyst are separate entities, and
      furthermore suggest their characteristic histology, pathogenesis, and biological
      behaviors.

PMID- 20801489
TI  - Technetium-99 ((99)Tc) in annual growth segments of knotted wrack (Ascophyllum
      nodosum).
AB  - The distribution of technetium-99 ((99)Tc) in annual growth segments of the brown
      seaweed Ascophyllum nodosum (Fucales, Phaeophyceae) from the southwestern coast
      of Norway is examined in samples collected from January to November 2006. A
      twenty-fold increase in the (99)Tc-concentration from the youngest to the oldest
      growth segments was found. The concentrations ranged from 42 to 98Bq/kg dry
      weight (d.w.) and from 964 to 1000Bq/kg d.w. in growth segments formed in 2006
      and 1996, respectively. In addition, a seasonal variation in the (99)Tc
      concentration was observed in the actively growing 2006-segments: concentrations
      decreased from 98Bq/kg d.w. in April to 54Bq/kg d.w. in June; there was a further
      reduction from June to August (42Bq/kg d.w.); and, finally there was an increase
      from August to November (93Bq/kg d.w.). In most of the segments formed between
      2000 and 2005, there was a tendency of slightly decreasing (99)Tc-concentrations
      between June and November but this pattern was not observed for the older growth
      segments. In order to find an explanation for the non-homogenous distribution of
      (99)Tc within thalli of A. nodosum, different hypotheses are discussed. Uptake
      and elimination of (99)Tc appears to be most pronounced in the actively growing
      segments. To date, such non-homogenous distribution of (99)Tc within thalli of A.
      nodosum has not been taken into consideration, neither in connection with sample
      collection nor analysis. This paper shows that special protocols must be followed
      if A. nodosum is going to be used as a bioindicator for (99)Tc in the marine
      environment. A sampling strategy is proposed.

PMID- 20801490
TI  - Environmental exposure of lead and iron deficit anemia in children age ranged 1-5
      years: a cross sectional study.
AB  - Iron (Fe) deficiency is the most common nutritional problem among children and
      lead (Pb) toxicity is the most common environmental health threat to children all
      over the world. The objective of this study was to determine blood lead (BPb)
      levels and prevalence of Fe deficient anemia among 1 to 5year old children
      attending day care clinic in pediatric ward of civil hospital Karachi, Pakistan.
      A total of 340 children of both genders participating in this study, were
      screened for anemia. Among them 215 were anemic and 125 non-anemic. The anemic
      group was further divided in two groups on the basis of % hemoglobin (Hb), mild
      (Hb <10g/dL) and severe anemic group (Hb <8g/dL), while non-anemic as referent
      children (Hb >10g/dL). The blood samples were analysed for Pb and Fe, along with
      hematological parameters. The result indicated that anemic children had a higher
      mean values of Pb in blood than referent children with Hb >10g/dL. The Pb levels
      <100MUg/L were detected in 40% referent children while 60% of them had >10MUg/dL.
      The BPb concentration in severe anemic children (53%) was found in the range of
      100-200MUg/L, whereas 47% had >200MUg/L. The significant negative correlations of
      BPb level with % Hb (r=-0.514 and r=-0.685) and Fe contents (r=-0.522, r=-0.762,
      p<0.001) were observed in mild and severe anemic children respectively. While
      positive correlation was observed between BPb and age of both group and genders
      (r=0.69, p<0.01). The BPb levels were significantly associated with biochemical
      indices in the blood which have the potential to be used as biomarkers of Pb
      intoxication and Fe deficient anemia.

PMID- 20801491
TI  - Robot-assisted tapered ureteral reimplantation for congenital megaureter.
AB  - OBJECTIVE: To discuss the clinical implications of primary obstructed congenital
      megaureter in the adult and illustrate a minimally-invasive approach for surgical
      intervention. METHODS: We present the case of a 51-year-old man with a
      longstanding history of symptomatic congenital megaureter, illustrating an
      approach for robot-assisted tapered ureteral reimplantation. Ureteral dissection,
      tapering, and nonrefluxing ureteroneocystostomy were all completed using a robot
      assisted laparoscopic technique. RESULTS: The total operative time was 262
      minutes, with an estimated blood loss of 150 mL. The patient's hospital course
      was uneventful, with discharge on postoperative day 4 without a Foley catheter or
      drain. A diuretic renal scan was performed at 5 months that showed good
      preservation of renal function with rapid clearance of tracer on the
      reconstructed side. The patient was pain free at his last follow-up visit without
      any symptoms. CONCLUSIONS: We have demonstrated a technique for robot-assisted
      tapered nonrefluxing ureteral reimplantation for congenital megaureter. Robotic
      assistance provided a safe and effective approach for complex ureteral
      reconstruction while minimizing morbidity.

PMID- 20801492
TI  - Squamous cell carcinoma within a horseshoe kidney with associated renal stones
      detected by computed tomography and magnetic resonance imaging.
AB  - We describe a 69-year-old man who came to our observation with a history of
      persistent left flank abdominal pain, fever for several weeks, and a previous
      history of passing renal stones. Radiological examinations with computed
      tomography and magnetic resonance imaging revealed a solid mass within the left
      side of a horseshoe kidney, with associated large renal stones. The patient
      subsequently underwent partial left nephrectomy. The final diagnosis was
      consistent with squamous cell carcinoma arising in a horseshoe kidney, with
      associated renal stones.

PMID- 20801493
TI  - Correlation and quantitation of microRNA aberrant expression in tissues and sera
      from patients with breast tumor.
AB  - OBJECTIVES: MicroRNAs (miRNAs) have been underlined as a promising potential
      biomarker for breast cancer but are limited to tissue specimens. Clinical
      specimens of sera are more abundant and more conveniently collected than tissues.
      This work was designed to investigate the expression and correlation of a
      selected panel of miRNAs associated with breast tumor in tissues and matching
      serum samples. METHODS: Tumor tissues, adjacent non-tumor tissues and matching
      serum samples were collected from 68 patients with newly diagnosed breast tumors.
      Normal control sera were collected from 40 healthy subjects. A panel of 6 miRNAs
      (miRNA-21, 106a, 126, 155, 199a and 335) were selected and their aberrant
      expression levels were quantified by using real-time PCR technique. RESULTS: A
      high correlation of miRNA expression level was found between breast tumor tissues
      and sera. MiR-21, miR-106a and miR-155 were significantly over-expressed in the
      tumor specimens compared with those in normal controls (P < 0.05), whereas miR
      126, miR-199a and miR-335 were significantly under-expressed (P < 0.05).
      Furthermore, the relative expression of miR-21, miR-126, miR-155, miR-199a and
      miR-335 was closely associated with clinicopathologic features of breast cancer
      (P < 0.05), such as histological tumor grades and sex hormone receptor
      expression. CONCLUSIONS: Selective expression and modulation of miRNAs could be
      potential blood-based biomarkers for breast cancer diagnosis, grading and
      prognosis. Our results should encourage further studies on the use of miRNAs in
      serum samples as an easy and convenient method of breast cancer screening.

PMID- 20801494
TI  - Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment
      with clopidogrel and prasugrel in the TRITON-TIMI 38 trial: a pharmacogenetic
      analysis.
AB  - BACKGROUND: Clopidogrel and prasugrel are subject to efflux via P-glycoprotein
      (encoded by ABCB1, also known as MDR1). ABCB1 polymorphisms, particularly 3435C
      >T, may affect drug transport and efficacy. We aimed to assess the effect of this
      polymorphism by itself and alongside variants in CYP2C19 on cardiovascular
      outcomes in patients treated with clopidogrel or prasugrel in TRITON-TIMI 38. We
      also assessed the effect of genotype on the pharmacodynamic and pharmacokinetic
      properties of these drugs in healthy individuals. METHODS: We genotyped ABCB1 in
      2932 patients with acute coronary syndromes undergoing percutaneous intervention
      who were treated with clopidogrel (n=1471) or prasugrel (n=1461) in the TRITON
      TIMI 38 trial. We evaluated the association between ABCB1 3435C->T and rates of
      the primary efficacy endpoint (cardiovascular death, myocardial infarction, or
      stroke) until 15 months. We then assessed the combined effect of ABCB1 3435C->T
      genotype and reduced-function alleles of CYP2C19. 321 healthy individuals were
      also genotyped, and we tested the association of genetic variants with reduction
      in maximum platelet aggregation and plasma concentrations of active drug
      metabolites. FINDINGS: In patients treated with clopidogrel, ABCB1 3435C->T
      genotype was significantly associated with the risk of cardiovascular death,
      myocardial infarction, or stroke (p=0.0064). TT homozygotes had a 72% increased
      risk of the primary endpoint compared with CT/CC individuals (Kaplan-Meier event
      rates 12.9% [52 of 414] vs 7.8% [80 of 1057 participants]; HR 1.72, 95% CI 1.22
      2.44, p=0.002). ABCB1 3435C->T and CYP2C19 genotypes were significant,
      independent predictors of the primary endpoint, and 681 (47%) of the 1454
      genotyped patients taking clopidogrel who were either CYP2C19 reduced-function
      allele carriers, ABCB1 3435 TT homozygotes, or both were at increased risk of the
      primary endpoint (HR 1.97, 95% CI 1.38-2.82, p=0.0002). In healthy participants,
      3435 TT homozygotes had an absolute reduction in maximum platelet aggregation
      with clopidogrel that was 7.3 percentage points less than for CT/CC individuals
      (p=0.0127). ABCB1 genotypes were not significantly associated with clinical or
      pharmacological outcomes in patients with an acute coronary syndrome or healthy
      individuals treated with prasugrel, respectively. INTERPRETATION: Individuals
      with the ABCB1 3435 TT genotype have reduced platelet inhibition and are at
      increased risk of recurrent ischaemic events during clopidogrel treatment. In
      patients with acute coronary syndromes who have undergone percutaneous
      intervention, when both ABCB1 and CYP2C19 are taken into account, nearly half of
      the population carries a genotype associated with increased risk of major adverse
      cardiovascular events while on standard doses of clopidogrel. FUNDING: Daiichi
      Sankyo Company Ltd and Eli Lilly and Company.

PMID- 20801495
TI  - Heart rate as a risk factor in chronic heart failure (SHIFT): the association
      between heart rate and outcomes in a randomised placebo-controlled trial.
AB  - BACKGROUND: Raised resting heart rate is a marker of cardiovascular risk. We
      postulated that heart rate is also a risk factor for cardiovascular events in
      heart failure. In the SHIFT trial, patients with chronic heart failure were
      treated with the selective heart-rate-lowering agent ivabradine. We aimed to test
      our hypothesis by investigating the association between heart rate and events in
      this patient population. METHODS: We analysed cardiovascular outcomes in the
      placebo (n=3264) and ivabradine groups (n=3241) of this randomised trial, divided
      by quintiles of baseline heart rate in the placebo group. The primary composite
      endpoint was cardiovascular death or hospital admission for worsening heart
      failure. In the ivabradine group, heart rate achieved at 28 days was also
      analysed in relation to subsequent outcomes. Analysis adjusted to change in heart
      rate was used to study heart-rate reduction as mechanism for risk reduction by
      ivabradine directly. FINDINGS: In the placebo group, patients with the highest
      heart rates (>or=87 beats per min [bpm], n=682, 286 events) were at more than two
      fold higher risk for the primary composite endpoint than were patients with the
      lowest heart rates (70 to <72 bpm, n=461, 92 events; hazard ratio [HR] 2.34, 95%
      CI 1.84-2.98, p<0.0001). Risk of primary composite endpoint events increased by
      3% with every beat increase from baseline heart rate and 16% for every 5-bpm
      increase. In the ivabradine group, there was a direct association between heart
      rate achieved at 28 days and subsequent cardiac outcomes. Patients with heart
      rates lower than 60 bpm at 28 days on treatment had fewer primary composite
      endpoint events during the study (n=1192; event rate 17.4%, 95% CI 15.3-19.6)
      than did patients with higher heart rates. The effect of ivabradine is accounted
      for by heart-rate reduction, as shown by the neutralisation of the treatment
      effect after adjustment for change of heart rate at 28 days (HR 0.95, 0.85-1.06,
      p=0.352). INTERPRETATION: Our analysis confirms that high heart rate is a risk
      factor in heart failure. Selective lowering of heart rates with ivabradine
      improves cardiovascular outcomes. Heart rate is an important target for treatment
      of heart failure. FUNDING: Servier, France.

PMID- 20801496
TI  - Efficacy and safety of dabigatran compared with warfarin at different levels of
      international normalised ratio control for stroke prevention in atrial
      fibrillation: an analysis of the RE-LY trial.
AB  - BACKGROUND: Effectiveness and safety of warfarin is associated with the time in
      therapeutic range (TTR) with an international normalised ratio (INR) of 2.0-3.0.
      In the Randomised Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial,
      dabigatran versus warfarin reduced both stroke and haemorrhage. We aimed to
      investigate the primary and secondary outcomes of the RE-LY trial in relation to
      each centre's mean TTR (cTTR) in the warfarin population. METHODS: In the RE-LY
      trial, 18 113 patients at 951 sites were randomly assigned to 110 mg or 150 mg
      dabigatran twice daily versus warfarin dose adjusted to INR 2.0-3.0. Median
      follow-up was 2.0 years. For 18 024 patients at 906 sites, the cTTR was estimated
      by averaging TTR for individual warfarin-treated patients calculated by the
      Rosendaal method. We compared the outcomes of RE-LY across the three treatment
      groups within four groups defined by the quartiles of cTTR. RE-LY is registered
      with ClinicalTrials.gov, number NCT00262600. FINDINGS: The quartiles of cTTR for
      patients in the warfarin group were: less than 57.1%, 57.1-65.5%, 65.5-72.6%, and
      greater than 72.6%. There were no significant interactions between cTTR and
      prevention of stroke and systemic embolism with either 110 mg dabigatran
      (interaction p=0.89) or 150 mg dabigatran (interaction p=0.20) versus warfarin.
      Neither were any significant interactions recorded with cTTR with regards to
      intracranial bleeding with 110 mg dabigatran (interaction p=0.71) or 150 mg
      dabigatran (interaction p=0.89) versus warfarin. There was a significant
      interaction between cTTR and major bleeding when comparing 150 mg dabigatran with
      warfarin (interaction p=0.03), with less bleeding events at lower cTTR but
      similar events at higher cTTR, whereas rates of major bleeding were lower with
      110 mg dabigatran than with warfarin irrespective of cTTR. There were significant
      interactions between cTTR and effects of both 110 mg and 150 mg dabigatran versus
      warfarin on the composite of all cardiovascular events (interaction p=0.036 and
      p=0.0006, respectively) and total mortality (interaction p=0.066 and p=0.052,
      respectively) with reduced event rates at low cTTR, and similar rates at high
      cTTR. INTERPRETATION: The benefits of 150 mg dabigatran at reducing stroke, 110
      mg dabigatran at reducing bleeding, and both doses at reducing intracranial
      bleeding versus warfarin were consistent irrespective of centres' quality of INR
      control. For all vascular events, non-haemorrhagic events, and mortality,
      advantages of dabigatran were greater at sites with poor INR control than at
      those with good INR control. Overall, these results show that local standards of
      care affect the benefits of use of new treatment alternatives. FUNDING:
      Boehringer Ingelheim.

PMID- 20801497
TI  - Response to antiplatelet treatment: from genes to outcome.

PMID- 20801498
TI  - Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of
      treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a
      genetic substudy of the PLATO trial.
AB  - BACKGROUND: In the PLATO trial of ticagrelor versus clopidogrel for treatment of
      acute coronary syndromes, ticagrelor reduced the composite outcome of
      cardiovascular death, myocardial infarction, and stroke, but increased events of
      major bleeding related to non-coronary artery bypass graft (CABG). CYP2C19 and
      ABCB1 genotypes are known to influence the effects of clopidogrel. In this
      substudy, we investigated the effects of these genotypes on outcomes between and
      within treatment groups. METHODS: DNA samples obtained from patients in the PLATO
      trial were genotyped for CYP2C19 loss-of-function alleles (*2, *3, *4, *5, *6,
      *7, and *8), the CYP2C19 gain-of-function allele *17, and the ABCB1 single
      nucleotide polymorphism 3435C->T. For the CYP2C19 genotype, patients were
      stratified by the presence or absence of any loss-of-function allele, and for the
      ABCB1 genotype, patients were stratified by predicted gene expression (high,
      intermediate, or low). The primary efficacy endpoint was the composite of
      cardiovascular death, myocardial infarction, or stroke after up to 12 months'
      treatment with ticagrelor or clopidogrel. FINDINGS: 10 285 patients provided
      samples for genetic analysis. The primary outcome occurred less often with
      ticagrelor versus clopidogrel, irrespective of CYP2C19 genotype: 8.6% versus
      11.2% (hazard ratio 0.77, 95% CI 0.60-0.99, p=0.0380) in patients with any loss
      of-function allele; and 8.8% versus 10.0% (0.86, 0.74-1.01, p=0.0608) in those
      without any loss-of-function allele (interaction p=0.46). For the ABCB1 genotype,
      event rates for the primary outcome were also consistently lower in the
      ticagrelor than in the clopidogrel group for all genotype groups (interaction
      p=0.39; 8.8%vs 11.9%; 0.71, 0.55-0.92 for the high-expression genotype). In the
      clopidogrel group, the event rate at 30 days was higher in patients with than in
      those without any loss-of-function CYP2C19 alleles (5.7%vs 3.8%, p=0.028),
      leading to earlier separation of event rates between treatment groups in patients
      with loss-of-function alleles. Patients on clopidogrel who had any gain-of
      function CYP2C19 allele had a higher frequency of major bleeding (11.9%) than did
      those without any gain-of-function or loss-of-function alleles (9.5%; p=0.022),
      but interaction between treatment and genotype groups was not significant for any
      type of major bleeding. INTERPRETATION: Ticagrelor is a more efficacious
      treatment for acute coronary syndromes than is clopidogrel, irrespective of
      CYP2C19 and ABCB1 polymorphisms. Use of ticagrelor instead of clopidogrel
      eliminates the need for presently recommended genetic testing before dual
      antiplatelet treatment. FUNDING: AstraZeneca.

PMID- 20801499
TI  - Quality of anticoagulation control in atrial fibrillation.

PMID- 20801501
TI  - Ivabradine in heart failure--no paradigm SHIFT...yet.

PMID- 20801502
TI  - Characterization, purification, and stability of gold nanoparticles.
AB  - Impurities in the synthesized gold nanoparticle (AuNP) solution are
      systematically identified followed by determining an optimal purification process
      and evaluating the stability as well as oxidation state of the purified 20-nm
      AuNPs. Quantified non-AuNP components and a newly speciated byproduct (acetate)
      complete the stoichiometric equation of AuNP synthesis through the citrate
      reduction method. Among the five tested centrifugation forces (3000-11,000g) and
      durations (10-60 min), optimal purification of AuNPs was achieved by
      centrifugation operating at 7000 g for 20 min which satisfactorily recovers ~80%
      of AuNPs without detectable impurities. Storage in the dark at 4  degrees C
      prolongs the stability of the purified AuNP suspensions up to 20 days. AuNPs
      employed in this study persist in their atomic status without being oxidized,
      even after they were aerosolized in air or heated at 500  degrees C. This work
      demonstrates how impurities are identified and removed, and the purified AuNPs
      can be a reference material to evaluate toxicity or reactivity of other
      engineered nanomaterials.

PMID- 20801504
TI  - Roles of TauT and system A in cytoprotection of rat syncytiotrophoblast cell line
      exposed to hypertonic stress.
AB  - The purpose of this study was to clarify the cytoprotective mechanism(s) induced
      in a conditionally immortalized syncytiotrophoblast cell line (TR-TBT 18d-1)
      exposed to hypertonic conditions. Hypertonicity-induced apoptosis of TR-TBT 18d-1
      cells, but this was blocked by addition of 1 mM taurine to the culture medium.
      TauT-knockdown using siRNA revealed that TauT is a major contributor to taurine
      uptake by TR-TBT 18d-1 cells, at least under normal conditions. Cellular uptake
      of [(3)H]taurine and [(14)C]betaine by TR-TBT 18d-1 cells cultured under
      hypertonic conditions was increased compared to that under normal conditions.
      TauT, BGT-1, ATA2 and HSP70 mRNAs were upregulated by hypertonicity, while OCTN2,
      ENT1 and CNT1 mRNAs were downregulated. [(3)H]Taurine uptake was strongly
      inhibited by TauT inhibitors such as hypotaurine and beta-alanine. MeAIB, a
      system A specific substrate, inhibited hypertonic stress-induced [(14)C]betaine
      uptake. These results suggest that TauT and system A play cytoprotective roles in
      syncytiotrophoblasts exposed to hypertonic stress.

PMID- 20801503
TI  - Helicoidal multi-lamellar features of RGD-functionalized silk biomaterials for
      corneal tissue engineering.
AB  - RGD-coupled silk protein-biomaterial lamellar systems were prepared and studied
      with human cornea fibroblasts (hCFs) to match functional requirements. A strategy
      for corneal tissue engineering was pursued to replicate the structural hierarchy
      of human corneal stroma within thin stacks of lamellae-like tissues, in this case
      constructed from scaffolds constructed with RGD-coupled, patterned, porous,
      mechanically robust and transparent silk films. The influence of RGD-coupling on
      the orientation, proliferation, ECM organization, and gene expression of hCFs was
      assessed. RGD surface modification enhanced cell attachment, proliferation,
      alignment and expression of both collagens (type I and V) and proteoglycans
      (decorin and biglycan). Confocal and histological images of the lamellar systems
      revealed that the bio-functionalized silk human cornea 3D constructs exhibited
      integrated corneal stroma tissue with helicoidal multi-lamellar alignment of
      collagen-rich and proteoglycan-rich extracellular matrix, with transparency of
      the construct. This biomimetic approach to replicate corneal stromal tissue
      structural hierarchy and architecture demonstrates a useful strategy for
      engineering human cornea. Further, this approach can be exploited for other
      tissue systems due to the pervasive nature of such helicoids in most human
      tissues.

PMID- 20801506
TI  - Copy number alterations at polymorphic loci may be acquired somatically in
      patients with myelodysplastic syndromes.
AB  - Loss of genomic integrity is thought to be one of the underlying causes of
      myelodysplastic syndromes (MDS). However, it is unclear whether changes in copy
      number at loci that are common sites of copy number polymorphisms play a
      pathogenic role. Here we show that copy number changes in the MDS clone that
      occur at polymorphic loci are frequently somatic alterations rather than
      constitutional variants, and the extent of copy number changes at polymorphic
      loci is increased in CD34(+) cells of MDS patients compared to age-matched
      controls. This study suggests a potential pathophysiological role for copy number
      alterations at polymorphic loci in patients with MDS, and highlights the need for
      somatic control tissues for each patient studied in high-resolution genome-wide
      investigations.

PMID- 20801505
TI  - STIM1, but not STIM2, is required for proper agonist-induced Ca2+ signaling.
AB  - The stromal interaction molecules STIM1 and STIM2 sense a decreasing Ca(2+)
      concentration in the lumen of the endoplasmic reticulum and activate Ca(2+)
      channels in the plasma membrane. In addition, at least 2 reports suggested that
      STIM1 may also interact with the inositol 1,4,5-trisphosphate (IP(3)) receptor.
      Using embryonic fibroblasts from Stim1(-/-), Stim2(-/-) and wild-type mice, we
      now tested the hypothesis that STIM1 and STIM2 would also regulate the IP(3)
      receptor. We investigated whether STIM1 or STIM2 would be the luminal Ca(2+)
      sensor that controls the loading dependence of the IP(3)-induced Ca(2+) release.
      Partial emptying of the stores in plasma-membrane permeabilized cells resulted in
      an increased EC(50) and a decreased Hill coefficient for IP(3)-induced Ca(2+)
      release. This effect occurred both in the presence and absence of STIM proteins,
      indicating that these proteins were not the luminal Ca(2+) sensor for the IP(3)
      receptor. Although Stim1(-/-) cells displayed a normal IP(3)-receptor function,
      agonist-induced Ca(2+) release was reduced. This finding suggests that the
      presence of STIM1 is required for proper agonist-induced Ca(2+) signaling. Our
      data do not provide experimental evidence for the suggestion that STIM proteins
      would directly control the function of the IP(3) receptor.

PMID- 20801507
TI  - Proteomic differentiation pattern in the U937 cell line.
AB  - The U937 cell line, originally established from a histiocytic lymphoma, has been
      widely used as a powerful in vitro model for haematological studies. These cells
      retain the immature cell phenotype and can be induced to differentiate by several
      factors, among which 12-O-tetradecanoyl-13-phorbol acetate (TPA). Fully
      differentiated cells acquire the adherent phenotype and exhibit various
      properties typical of macrophages. However, in spite of a great deal of research
      devoted to the U937 cellular model, the molecular basis of biological processes
      involved in the monocyte/macrophage differentiation remains unclear. The present
      study has been undertaken to contribute to this knowledge, in order to identify
      proteomic-based differentiation pattern for the U937 cells exposed to TPA.
      Present results have highlighted that the U937 cell differentiation is correlated
      with a significant proteomic modulation, corresponding to about 30% of the
      identified proteins, including both over- and down-regulated proteins. Negative
      modulation regarded proteins involved in the regulation of cell proliferation and
      in metabolic processes. Proteins appearing incremented in macrophagic phenotype
      include calcium- and phospholipid-binding proteins and several proteins related
      to the phagocytic activity. Conclusively, we suggest that this new set of
      differentially expressed proteins may represent meaningful myelo-monocytic
      differentiation markers to be applied to the study of several haematological
      diseases.

PMID- 20801508
TI  - Assessment of the health status of mussels Mytilus galloprovincialis along
      Thermaikos Gulf (Northern Greece): an integrative biomarker approach using
      ecosystem health indices.
AB  - Pollution biomarkers were assessed in the digestive gland of mussels Mytilus
      galloprovincialis collected from Greek coasts (Thermaikos and Strymonikos Gulf,
      Northern Greece) on July 2004. The values of biomarkers were integrated using
      three ecosystem health indices: health status index (HIS) calculated by the
      expert system, lysosomal response index (LRI) and integrated biomarker response
      (IBR). The HIS is based on the integration of the biomarker values, classifying
      the health status of mussels according to pollution degree. The LRI combines two
      lysosomal responses (lysosomal membrane stability and lysosomal structural
      changes) in a single index, which is associated with the ecosystem contamination.
      The IBR is a useful tool for the visualization of biological responses in marine
      environments. The results support the use of HIS and LRI as powerful tools for
      the qualitative and quantitative evaluation of environmental stress, while
      enhance the use of IBR as a constructive method for the qualitative
      discrimination of contaminated sites. HIS and LRI revealed high stress conditions
      in all sampling stations of Thermaikos gulf, whereas unstressed conditions were
      detected in Olympiada (reference station) by the use of HIS and low stress
      conditions were shown by the use of LRI. The IBR illustrated higher levels of
      stress in mussels collected from Thermaikos Gulf, compared to mussels gathered
      from the reference station. The advantages and disadvantages of the HIS, LRI and
      IBR are also discussed.

PMID- 20801509
TI  - Effects of ZnO nanomaterials on Xenopus laevis growth and development.
AB  - The objectives of this study were to quantify uptake and developmental effects of
      zinc oxide nanomaterials (nano-ZnO) on Xenopus laevis throughout the metomormosis
      process. To accomplish this, X. laevis were exposed to aqueous suspensions of 40
      100 nm nano-ZnO beginning in-ovo and proceeding through metamorphosis.
      Nanomaterials were dispersed via sonication methods into reconstituted moderately
      hard water test solutions. A flow-through system was utilized to decrease the
      likelihood of depletion in ZnO concentration. Exposure to 2 mg/L nano-ZnO
      significantly increased mortality incidence to 40% and negatively affected
      metamorphosis of X. laevis. Tadpoles exposed to 2 mg/L nano-ZnO developed slower
      as indicated by tadpoles with an average stage of 56 at the conclusion of the
      study which was significantly lower than the control tadpole stages. No tadpoles
      exposed to 2 mg/L of nano-ZnO completed metamorphosis by the conclusion of the
      study. Tadpoles exposed to 0.125 mg/L nano-ZnO experienced faster development
      along with larger body measurements indicating that low dose exposure to nano-ZnO
      can stimulate growth and metamorphosis of X. laevis.

PMID- 20801510
TI  - Dietary intake and potential health risk of DDTs and PBDEs via seafood
      consumption in South China.
AB  - A total of 602 seafood samples, including fish, shrimps, crabs and molluscs, were
      analyzed for a suite of persistent halogenated compounds. The residual levels of
      DDTs (sum of o,p'- and p,p'-DDT, DDD, and DDE) and polybrominated diphenyl ethers
      (PBDEs) varied significantly among different species, and ranged from non
      detectable (nd) to 699 ng/g and nd to 5.93 ng/g, respectively. Comparison of the
      levels of DDTs and PBDEs in mussel samples worldwide suggested that South China
      is probably one of the most DDT-polluted areas, but is moderate at most in terms
      of PBDE contamination. Combined with a recent dietary survey at the same sampling
      locations, dietary intakes of DDTs and PBDEs by local residents via seafood
      consumption for all age groups were estimated to be 147-564 and 4.7-18.5 ng/day,
      or 8.5-12.9 and 0.27-0.46 g/kg bw/day, respectively. Among the different seafood
      types, fish contributed the largest portion of the dietary intakes of DDTs (57%),
      followed by molluscs (38%). Similarly, the dietary intakes of PBDEs were also
      dominated by fish (45%) and molluscs (45%). Assessment based on several available
      guidelines suggested that though no significant human health risk associated with
      the dietary intake of PBDEs, a lifetime cancer risk from dietary exposure to DDTs
      remains a probability. Because dietary intake of DDTs was dominated by fish and
      molluscs, added concern should be paid to fish and molluscs.

PMID- 20801511
TI  - All oligosaccharide moieties of the MU chains in the pre-BCR are of the high
      mannose type.
AB  - Although it is well established that pre-BCR signaling governs proliferation and
      differentiation during B cell development, the components of the pre-BCR that are
      important for signaling are a matter of controversy. It has been suggested that
      signaling by the MU heavy chains of the pre-BCR induces survival and
      differentiation of pre-B cells, while the lambda5 part of the pre-BCR is
      essential for proliferation and clonal expansion. However, the mechanism by which
      pre-BCR MU chains initiate differentiation signals is not clear. Using two
      variants of a murine B-lymphocyte cell line that differ only in surface
      expression of either BCR or pre-BCR, we demonstrated that surface MU chains in
      the pre-BCR are of the high-mannose type only, while those in the BCR are of the
      complex type. It is hypothesized that mannose-specific lectin-like molecules on
      accessory cells or in solution may function as the non-antigen ligand that
      triggers the pre-BCR.

PMID- 20801512
TI  - Decoy receptor 3 protects non-obese diabetic mice from autoimmune diabetes by
      regulating dendritic cell maturation and function.
AB  - Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor
      superfamily, regulates immune responses through competing with receptors of Fas
      ligand (FasL), LIGHT and TNF-like molecule 1A (TL1A). We have previously
      demonstrated that transgenic expression of DcR3 in a beta cell-specific manner
      significantly protects non-obese diabetic (NOD) mice from autoimmune diabetes. In
      this study, we further investigated the systemic effect of DcR3 in regulating
      lymphocytes and dendritic cells in NOD mice. Our results demonstrated that both
      DcR3 plasmid and protein treatments significantly inhibited insulitis and
      diabetes. Lymphocytes from DcR3.Fc-treated mice revealed less proliferative
      potential and transferred ameliorated diabetes. By administration of DcR3.Fc in
      T1 and T2 double transgenic NOD mice expressing human Thy1 or murine Thy1.1
      surface marker under IFN-gamma or IL-4 promoter control respectively, we observed
      a remarkable reduction of Th1 and an increase of Th2 immune responses in vivo.
      Strikingly, in vitro polarization experiments exhibited that not only Th1 but
      also Th17 cell differentiation was significantly inhibited in splenocytes treated
      with DcR3.Fc protein. However, this phenomenon was only observed in splenocytes,
      not in purified CD4(+) T cells, suggesting that DcR3-mediated inhibition of Th1
      and Th17 differentiation is not T cell-autonomous and maybe through other cell
      types such as dendritic cells. Finally, our results demonstrated that DcR3
      directly modulates the differentiation and maturation of dendritic cells and
      subsequently regulates the differentiation and effector function of T cells.

PMID- 20801513
TI  - Low intraocular pressure resulting from ciliary body detachment in patients with
      myotonic dystrophy.
AB  - PURPOSE: To investigate why myotonic dystrophy type 1 (DM1) patients have low
      intraocular pressure (IOP). DESIGN: Prospective, comparative case series.
      PARTICIPANTS: One hundred two eyes of 51 patients with DM1 (age range, 21-64
      years) and 44 eyes of 22 healthy subjects of similar age (21-64 years). METHODS:
      All participants underwent IOP measurement with Goldmann applanation tonometry
      and an in vivo examination of the ciliary body with a 35-MHz high-resolution B
      scan. The findings were compared between the 2 groups. In both groups, only
      patients with no history of ocular trauma or surgery were included. The
      differences were evaluated using the unpaired Student t test. MAIN OUTCOME
      MEASUREMENTS: Intraocular pressure, central corneal thickness (CCT), and
      echographic evidence of ciliary body detachment. RESULTS: The mean +/- standard
      deviation (SD) IOP in patients with DM1 was 10.9 +/- 3.1 mmHg and that in the
      control patients was 15.4 +/- 2.2 mmHg, a difference that reached significance
      (P<0.01). The mean +/- SD CCT (measured at the pupillary center) was 574.4 +/-
      37.9 MUm in the patients with DM1 and 557.8 +/- 39.2 MUm in the controls (P =
      0.02). Detachment of the ciliary body was identified in all DM1 subjects. Size
      was variable and the detachment involved 1 or more quadrants. The number of
      quadrants affected by the detachment was not correlated with the IOP (R(2) =
      0.088) or the size of the CTG expansion. No detachments were found in the healthy
      controls. CONCLUSIONS: Detachment of the ciliary body may explain the low IOP
      values in patients with DM1. The finding of a ciliary body detachment in an
      individual who has not had recent eye surgery or trauma raises the possibility of
      a DM1 diagnosis.

PMID- 20801514
TI  - Prevalence of cataract in an older population in India: the India study of age
      related eye disease.
AB  - PURPOSE: To describe the prevalence of cataract in older people in 2 areas of
      north and south India. DESIGN: Population-based, cross-sectional study.
      PARTICIPANTS: Randomly sampled villages were enumerated to identify people aged
      >= 60 years. Of 7518 enumerated people, 78% participated in a hospital-based
      ophthalmic examination. METHODS: The examination included visual acuity
      measurement, dilatation, and anterior and posterior segment examination. Digital
      images of the lens were taken and graded by type and severity of opacity using
      the Lens Opacity Classification System III (LOCS III). MAIN OUTCOME MEASURES: Age
      and gender-standardized prevalence of cataract and 95% confidence intervals
      (CIs). We defined type of cataract based on the LOCS III grade in the worse eye
      of: >= 4 for nuclear cataract, >= 3 for cortical cataract, and >= 2 for posterior
      subcapsular cataract (PSC). Any unoperated cataract was based on these criteria
      or ungradable dense opacities. Any cataract was defined as any unoperated or
      operated cataract. RESULTS: The prevalence of unoperated cataract in people aged
      >= 60 was 58% in north India (95% CI, 56-60) and 53% (95% CI, 51-55) in south
      India (P = 0.01). Nuclear cataract was the most common type: 48% (95% CI, 46-50)
      in north India and 38% (95% CI, 37-40) in south India (P<0.0001); corresponding
      figures for PSC were 21% (95% CI, 20-23) and 17% (95% CI, 16-19; P = 0.003),
      respectively, and for cortical cataract 7.6% (95% CI, 7-9) and 10.2% (95% CI, 9
      11; P<0.004). Bilateral aphakia/pseudophakia was slightly higher in the south
      (15.5%) than in the north (13.2%; P<0.03). The prevalence of any cataracts was
      similar in north (73.8%) and south India (71.8%). The prevalence of unoperated
      cataract increased with age and was higher in women than men (odds ratio [OR],
      1.8). Aphakia/pseudophakia was also more common in women, either unilateral (OR,
      1.2; P<0.02) or bilateral (OR, 1.3; P<0.002). CONCLUSIONS: We found high rates of
      unoperated cataract in older people in north and south India. Posterior
      subcapsular cataract was more common than in western studies. Women had higher
      rates of cataract, which was not explained by differential access to surgery.

PMID- 20801515
TI  - Role of confocal microscopy in the diagnosis of fungal and acanthamoeba
      keratitis.
AB  - PURPOSE: To investigate the role of confocal microscopy as a diagnostic modality
      in microbial keratitis and to determine inter- and intraobserver variation in the
      analysis and interpretation of confocal microscopy findings. DESIGN: Prospective,
      double masked, nonrandomized, observational clinical trial. PARTICIPANTS: We
      included 146 consecutive patients with clinically suspected microbial keratitis.
      METHODS: Confocal microscopy and microbiology evaluation of study participants.
      MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative
      predictive values of confocal microscopy in diagnosing fungal and Acanthamoeba
      keratitis compared with microbiologic evaluation, as well as the intra- and
      interobserver variation in interpretation of confocal scans. RESULTS: We included
      148 cases of infiltrative keratitis. Of the 103 microbiologically proven cases of
      Acanthamoeba or fungal keratitis, the confocal microscope was able to identify
      fungal filaments or Acanthamoeba cysts in 91 cases with either fungal or
      Acanthamoeba keratitis with a sensitivity of 88.3% (95% confidence interval [CI],
      82.2-94.5) and a specificity of 91.1% (95% CI, 82.8-99.4). The interobserver
      agreement in interpreting the scans was good (kappa = 0.6; phi = 0.617). The
      intraobserver agreement was kappa = 0.795 and phi = 0.807. CONCLUSIONS: The
      confocal microscope seems to be an accurate and reliable diagnostic modality in
      the etiologic diagnosis of fungal and Acanthamoeba keratitis.

PMID- 20801516
TI  - Simultaneous mutation detection in 90 retinal disease genes in multiple patients
      using a custom-designed 300-kb retinal resequencing chip.
AB  - PURPOSE: To develop a high-throughput, cost-effective diagnostic strategy for the
      identification of known and new mutations in 90 retinal disease genes. DESIGN:
      Evidence-based study. PARTICIPANTS: Sixty patients with a variety of retinal
      disorders, including Leber's congenital amaurosis, ocular albinism,
      pseudoxanthoma elasticum, retinitis pigmentosa, and Stargardt's disease. METHODS:
      We designed a custom 300-kb resequencing chip. Polymerase chain reaction (PCR)
      amplification, DNA fragmentation, and chip hybridization were performed according
      to Affymetrix recommendations. Hybridization signals were analyzed using Sequence
      pilot module seq-C mutation detection software (2009). This resequencing approach
      was validated by Sanger sequence technology. MAIN OUTCOME MEASURES: Disease
      causing sequence changes. RESULTS: We developed a retinal resequencing chip that
      covers all exons of 90 retinal disease genes. We developed and tested multiplex
      primer sets for 1445 amplicons representing the genes included on the chip. We
      validated our approach by screening 87 exons from 25 retinal disease genes
      containing 87 known sequence changes previously identified in our patient group
      using Sanger sequencing. Call rates for successfully hybridized amplicons were
      98% to 100%. Of the known single nucleotide changes, 99% could be detected on the
      chip. As expected, deletions could not be detected reliably. CONCLUSIONS: We
      designed a custom resequencing chip that can detect known and new sequence
      changes in 90 retinal disease genes using a new high-throughput strategy with a
      high sensitivity and specificity for one tenth of the cost of conventional direct
      sequencing. The developed amplification strategy allows for the pooling of
      multiple patients with non-overlapping phenotypes, enabling many patients to be
      analyzed simultaneously in a fast and cost-effective manner.

PMID- 20801517
TI  - Spectral transmittance of intraocular lenses under natural and artificial
      illumination: criteria analysis for choosing a suitable filter.
AB  - PURPOSE: To compare the spectral transmission of different intraocular lenses
      (IOLs) with either ultraviolet (UV) or blue-light filters, and to analyze the
      performance of these filters with artificial light sources as well as sunlight.
      DESIGN: Experimental study. METHODS: The spectral transmission curve of 10 IOLs
      was measured using a PerkinElmer Lambda 800 UV/VIS spectrometer (Waltham, MA).
      Different filtering simulations were performed using the D65 standard illuminant
      as daylight and standard incandescent lamp and fluorescent bulb illuminants. MAIN
      OUTCOMES MEASURES: Spectral transmittance of the IOLs. RESULTS: All the IOLs
      studied provide good UVC (200-280 nm) and UVB (280-315 nm) protection, except for
      one that presented an appreciable window at 270 nm. Nevertheless, both natural
      and artificial sources have practically no emission under 300 nm. In the UVA (315
      380 nm) range the curves of the different IOLs manifested different degrees of
      absorption. CONCLUSIONS: Not all the UV filters incorporated in different IOLs
      protect equally. The filters that provide greater photoprotection against UV
      radiation, even blue light, are yellow and orange. Then, yellow and orange IOL
      filters may be best suited for cases requiring special retinal protection. The
      filters that favor better photoreception of visible light (380-780 nm) are those
      that transmit this radiation close to 100%. Artificial illumination practically
      does not emit in the UV range, but its levels of illumination are very low when
      compared with solar light. A possible balance between photoprotection and
      photoreception could be a sharp cutoff filter with the cutoff wavelength near 400
      nm and a maximum transmittance around 100%.

PMID- 20801518
TI  - Slow enlargement of choroidal nevi: a long-term follow-up study.
AB  - PURPOSE: Choroidal nevi are generally considered to be stable lesions, and growth
      of a choroidal nevus is usually believed to be a sign of malignant
      transformation. We performed this study to determine whether choroidal nevi
      enlarge over a long period of follow-up without undergoing malignant
      transformation. DESIGN: Retrospective observational case series. PARTICIPANTS: A
      total of 278 patients with 284 nevi who had at least 7 years of photographic
      follow-up without clinical signs of transformation into melanoma were included in
      the study. METHODS: Data on demographic and clinical information were extracted
      from patients' charts. Detailed fundus drawings and color fundus photographs were
      reviewed and compared for evidence of enlargement. MAIN OUTCOME MEASURES: Nevus
      enlargement without clinical evidence of transformation into melanoma. RESULTS:
      Of the 278 patients, 69% were female and more than 99% were White with a median
      age at presentation of 57 years (range, 4-87 years). The largest nevus basal
      diameter was a median of 5 mm (range, 0.5-14 mm), and the median thickness was
      1.5 mm (range, 0.1-3.6 mm). Only 14 nevi (5%) had subretinal fluid outside the
      nevus, and 6% showed overlying orange pigment. Overlying retinal pigment
      epithelial alterations included drusen (61%), atrophy (6%), hyperplasia (10%),
      and fibrous metaplasia (6%). Of 284 nevi, 31% showed slight enlargement over a
      mean follow-up of 15 years. The median increase in diameter was 1 mm (mean, 0.9
      mm; range, 0.2-3.0 mm), and the median rate of enlargement was 0.06 mm/yr (mean,
      0.06 mm/yr; range, 0.01-0.36 mm/yr). None of the lesions that enlarged developed
      new risk factors that are generally associated with malignant transformation.
      Frequency of enlargement was 54% in patients aged less than 40 years and 19% in
      patients aged more than 60 years. On multivariate analysis, younger patient age
      was the only factor predictive of nevus enlargement (P<0.001). CONCLUSIONS: With
      long-term follow up, 31% of choroidal nevi showed slight enlargement without
      clinical evidence of transformation into melanoma. The frequency of enlargement
      was inversely related to patient age.

PMID- 20801519
TI  - The concave iris in pigment dispersion syndrome.
AB  - OBJECTIVE: To visualize the changes of the iris contour in patients with pigment
      dispersion syndrome after blinking, accommodation, and pharmacologic miosis using
      anterior segment optical coherence tomography. DESIGN: Observational case series.
      PARTICIPANTS: A total of 33 eyes of 20 patients with pigment dispersion syndrome.
      METHODS: Each eye was imaged along the horizontal 0- to 180-degree meridian using
      the Visante Anterior Segment Imaging System (Carl Zeiss Meditec, Dublin, CA).
      Scans were performed at baseline and after focusing on an internal fixation
      target for 5 minutes, forced blinking, accommodation, and pharmacologic miosis
      with pilocarpine 2%. MAIN OUTCOME MEASURES: Quantitative analysis of the changes
      in the iris configuration. RESULTS: After 5 minutes of continual fixation, the
      iris became planar with the mean +/- standard deviation curvature decreasing from
      214 +/- 74 MUm to 67 +/- 76 MUm (P < 0.05). The iris remained planar in all
      patients with pigment dispersion syndrome after forced blinking, but the iris
      concavity recovered to 227 +/- 113 MUm (P = 0.34) and 238 +/- 119 MUm (P = 0.19)
      with the -3.0 and -6.0 diopter lenses, respectively. Pilocarpine-induced miosis
      caused the iris to assume a planar configuration in all subjects. CONCLUSIONS:
      This study shows that the iris in pigment dispersion syndrome assumes a planar
      configuration when fixating and that the concavity of the iris surface is not
      restored by blinking. Accommodation restored the iris concavity, suggesting that
      the posterior curvature of the iris in pigment dispersion syndrome is induced and
      probably maintained, at least in part, by accommodation.

PMID- 20801520
TI  - Vitreoretinal surgery for severe retinal capillary hemangiomas in von hippel
      lindau disease.
AB  - PURPOSE: To evaluate the long-term success rate of vitreoretinal surgery for
      severe cases of retinal capillary hemangiomas (RCHs) caused by von Hippel-Lindau
      (VHL) disease. DESIGN: Retrospective case series. PARTICIPANTS: Twenty-three eyes
      of 21 patients with severe exudative or tractional retinal detachment caused by
      RCH, who had undergone vitreoretinal surgery. Patients' age at initial surgery
      ranged from 12 to 47 years (median, 27 years), and the fellow eye was already
      blind in 6 of 21 patients. INTERVENTIONS: All eyes underwent pars plana
      vitrectomy with posterior hyaloid detachment epiretinal membrane dissection and
      silicone oil or gas injection. In 9 eyes, retinectomy was performed to remove the
      RCH (group R). In the other 14 eyes, the RCH was treated by laser
      endophotocoagulation alone or combined with transscleral cryotherapy (group L).
      MAIN OUTCOME MEASURES: Visual acuity (preoperative, 6 and 18 months
      postoperatively), rate of RCH recurrence, and postoperative complications.
      RESULTS: In group R, an average of 2 operations per patient was needed. Six
      months after surgery, the retina was flat in 8 eyes. Mean follow-up was 8 years.
      Long-term complications included RCH reproliferation and neovascular glaucoma in
      4 eyes, 4 to 8 years after initial surgery. In the remaining 5 eyes, visual
      acuity ranged from 20/320 to counting fingers 18 months postoperatively. In group
      L, an average of 1.7 operations was needed. Six months after surgery, the retina
      was flat in 13 of 14 eyes. Mean follow-up was 4 years. New RCH occurred in 10
      eyes and required laser treatment. In the long term, 1 eye became blind after 5
      years because of aggressive RCH reproliferation and neovascular glaucoma, and 2
      eyes became blind after 10 years because of exudative retinal detachment. In the
      11 remaining eyes, visual acuity ranged from 20/320 to 20/20 (median: 20/50) 18
      months postoperatively. CONCLUSIONS: Vitreoretinal surgery is an effective
      treatment for severe VHL retinal hemangiomas. Large RCHs were satisfactorily
      treated by (1) vitrectomy with epiretinal dissection and endolaser
      photocoagulation or (2) retinectomy for RCH resection, although a high rate of
      vision-threatening RCH recurrence was observed in the long term. However in most
      cases, surgery improved or prolonged visual function in these eyes.

PMID- 20801521
TI  - Development of a risk score for geographic atrophy in complications of the age
      related macular degeneration prevention trial.
AB  - OBJECTIVE: To develop a risk score for developing geographic atrophy (GA)
      involving easily obtainable information among patients with bilateral large
      drusen. DESIGN: Cohort study within a multicenter randomized clinical trial.
      PARTICIPANTS: We included 1052 participants with >= 10 large (>125 MUm) drusen
      and visual acuity >= 20/40 in each eye. METHODS: In the Complications of Age
      related Macular Degeneration (AMD) Prevention Trial (CAPT), 1 eye of each
      participant was randomly assigned to laser treatment and the contralateral eye
      was assigned to observation to evaluate whether laser treatment of drusen could
      prevent vision loss. Gradings by a reading center were used to identify: CAPT end
      point GA (total area of GA [>250 MUm] > 1 disc area), GA (>175 MUm) involving the
      foveal center (CGA), and GA of any size and location (any GA). Established risk
      factors (age, smoking status, hypertension, Age-related Eye Disease Study simple
      severity scale score), both with and without a novel risk factor (night vision
      score), were used in assigning risk points. The risk scores were evaluated for
      the ability to discriminate and calibrate GA risk. MAIN OUTCOME MEASURES:
      Development of end point GA, CGA, and any GA. RESULTS: Among 942 CAPT
      participants who completed 5 years of follow-up and did not have any GA at
      baseline, 6.8% participants developed CAPT end point GA, 9.6% developed CGA, and
      34.4% developed any GA. The 5-year incidence of end point GA in 1 or both eyes of
      a participant increased with the 15-point GA risk score, from 0.6% for <7 points
      to 15% for >= 12 points. The 5-factor risk score predicted development of GA
      moderately well with the area under the receiver operating characteristic curve
      (AUC) 0.76 (95% confidence interval [CI], 0.71-0.81) for end point GA; 0.76 (95%
      CI, 0.71-0.80) for CGA, and 0.68 (95% CI, 0.65-0.72) for any GA. Prediction from
      the risk score without the night vision score had lower AUCs (range, 0.67-0.72).
      CONCLUSIONS: If validated in other patients, the GA risk score will be useful for
      identifying high-risk patients for clinical trials of prevention of GA and for
      clinical assessment of GA risk in early AMD patients.

PMID- 20801522
TI  - Effect of optic nerve sheath fenestration on papilledema of the operated and the
      contralateral nonoperated eyes in idiopathic intracranial hypertension.
AB  - PURPOSE: To evaluate the effect of optic nerve sheath fenestration (ONSF) on
      papilledema grade in the operated eyes and the contralateral nonoperated fellow
      eyes in patients with idiopathic intracranial hypertension (IIH). DESIGN:
      Retrospective review. PARTICIPANTS: A total of 78 patients underwent ONSF, and 20
      patients served as controls. METHODS: Charts of patients with IIH who had ONSF at
      the University of Iowa Hospital and Clinics were reviewed for age, gender, body
      mass index, and clinical findings. Optic disc photographs were graded by a masked
      observer using the Frisen papilledema grading scale at preoperative baseline and
      postoperatively at 2 weeks, 3 months, 6 months, and 12 months follow-up. Wilcoxon
      signed-rank test was used to examine the change in papilledema grade in both
      operated and nonoperated eyes at each time point. MAIN OUTCOME MEASURES: Grade of
      papilledema. RESULTS: Sixty-two patients (52 women and 10 men) with a mean age of
      32 years (range, 13-57 years) underwent unilateral ONSF. The median grade of
      papilledema for operated and nonoperated eyes was 3 and 2, respectively, at
      preoperative baseline. Postoperatively the grade was 2 in each eye at 2 weeks
      (P<0.0001 and <0.0002 for operated and nonoperated eyes, respectively), 1 in each
      eye at 3 months (P<0.0001 for both operated and nonoperated eyes), 1 in each eye
      at 6 months (P<0.0001 for both operated and nonoperated eyes), and 0.5 and 1 for
      operated and nonoperated eyes, respectively, at 12 months follow-up (P<0.0001 for
      both operated and nonoperated eyes). There was no significant difference in grade
      of disc edema or reduction of disc edema on the basis of age, gender, or body
      mass index. CONCLUSIONS: Unilateral ONSF significantly decreases the grade of
      papilledema in both ipsilateral (operated) and contralateral (unoperated) eyes.
      The reduction of the papilledema and the stability of visual field in the
      contralateral (nonoperated) eyes suggest that bilateral ONSF may not always be
      necessary in patients with bilateral visual loss and papilledema due to IIH.

PMID- 20801523
TI  - Glia atrophy in the hippocampus of chronic unpredictable stress-induced
      depression model rats is reversed by electroacupuncture treatment.
AB  - BACKGROUND: Growing evidence indicates that glia atrophy contributes to the
      pathophysiology and possibly the pathogenesis of major depressive disorder.
      Electroacupuncture (EA), one of Chinese traditional therapy, has potent
      antidepressant-like effect in many clinical studies. The mechanism by which EA
      improves behavioral deficits is still unclear. METHOD: Chronic unpredictable
      stress (CUS)-induced depression model rats were used to study the effect of EA
      treatment. EA was performed on acupoints 'Bai-Hui' (Du 20) and unilateral 'An
      Mian' (EX 17) once daily for three consecutive weeks, two weeks post CUS
      procedure. The antidepressant-like effect of EA treatment was analyzed by
      physical state (PS) and open field test (OFT). Astrocytic marker glial fibrillary
      acidic protein (GFAP) level in the hippocampus was detected by
      immunohistochemistry, Western blot analysis and reverse transcription-polymerase
      chain reaction (RT-PCR). RESULTS: Exposure to CUS resulted in a decrease of
      behavioral activity, whereas a daily session of EA treatment significantly
      reversed the behavioral deficit of these depression model rats. Moreover, the
      levels of GFAP mRNA and protein were decreased in the hippocampus of depression
      model rats. Intriguingly, EA treatment blocked effectively the decreased GFAP
      level. LIMITATION: The relative small number of the depression model rats may
      cause some bias of behavioral tests. CONCLUSION: EA has potential antidepressant
      like effect on CUS-induced depression model rats, which might be mediated by
      affecting the glial atrophy in the hippocampus.

PMID- 20801524
TI  - Comparing adult and adolescent transsexuals: an MMPI-2 and MMPI-A study.
AB  - Sex, sexual orientation and age have been shown to be important in relation to
      psychological functioning in transsexuals. However, only few studies to date took
      these factors into account and not earlier have adolescent transsexuals
      participated. In this study the Minnesota Multiphasic Personality Inventory (MMPI
      2 or MMPI-A, respectively) was administered to 293 adults (207 male to female
      transsexuals (MtFs), mean age 38.04 (range 18.56-65.62) and 86 female to male
      transsexuals (FtMs), mean age 33.26 (range 18.95-64.30)) and 83 adolescents (43
      MtFs, mean age 15.70 (range 13.16-18.70) and 40 FtMs, mean age 15.64 (range 13.05
      18.56)) with a gender identity disorder (GID). Of adult MtFs, 33% were
      categorized as "homosexuals" and 66% as "non-homosexuals". Of adult FtMs, 77%
      were categorized as "homosexuals" and 33% as "non-homosexuals". Adult FtMs
      functioned significantly better than MtFs on three clinical scales. Contrary to
      what is often assumed, no differences in psychological functioning were found in
      the adult transsexuals with regard to sexual orientation, except on one clinical
      scale. Most remarkably, significantly more adults with GID scored in the clinical
      range on two or more clinical scales than adolescents with GID. Therefore, early
      medical intervention may be recommendable for adolescents with GID.

PMID- 20801500
TI  - Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo
      controlled study.
AB  - BACKGROUND: Chronic heart failure is associated with high mortality and
      morbidity. Raised resting heart rate is a risk factor for adverse outcomes. We
      aimed to assess the effect of heart-rate reduction by the selective sinus-node
      inhibitor ivabradine on outcomes in heart failure. METHODS: Patients were
      eligible for participation in this randomised, double-blind, placebo-controlled,
      parallel-group study if they had symptomatic heart failure and a left-ventricular
      ejection fraction of 35% or lower, were in sinus rhythm with heart rate 70 beats
      per min or higher, had been admitted to hospital for heart failure within the
      previous year, and were on stable background treatment including a beta blocker
      if tolerated. Patients were randomly assigned by computer-generated allocation
      schedule to ivabradine titrated to a maximum of 7.5 mg twice daily or matching
      placebo. Patients and investigators were masked to treatment allocation. The
      primary endpoint was the composite of cardiovascular death or hospital admission
      for worsening heart failure. Analysis was by intention to treat. This trial is
      registered, number ISRCTN70429960. FINDINGS: 6558 patients were randomly assigned
      to treatment groups (3268 ivabradine, 3290 placebo). Data were available for
      analysis for 3241 patients in the ivabradine group and 3264 patients allocated
      placebo. Median follow-up was 22.9 (IQR 18-28) months. 793 (24%) patients in the
      ivabradine group and 937 (29%) of those taking placebo had a primary endpoint
      event (HR 0.82, 95% CI 0.75-0.90, p<0.0001). The effects were driven mainly by
      hospital admissions for worsening heart failure (672 [21%] placebo vs 514 [16%]
      ivabradine; HR 0.74, 0.66-0.83; p<0.0001) and deaths due to heart failure (151
      [5%] vs 113 [3%]; HR 0.74, 0.58-0.94, p=0.014). Fewer serious adverse events
      occurred in the ivabradine group (3388 events) than in the placebo group (3847;
      p=0.025). 150 (5%) of ivabradine patients had symptomatic bradycardia compared
      with 32 (1%) of the placebo group (p<0.0001). Visual side-effects (phosphenes)
      were reported by 89 (3%) of patients on ivabradine and 17 (1%) on placebo
      (p<0.0001). INTERPRETATION: Our results support the importance of heart-rate
      reduction with ivabradine for improvement of clinical outcomes in heart failure
      and confirm the important role of heart rate in the pathophysiology of this
      disorder. FUNDING: Servier, France.

PMID- 20801525
TI  - Re-examination of the seasonality of suicide in Taiwan during 1991-2008: a
      population-based study.
AB  - The purpose of the present study was to re-examine the monthly distribution of
      suicide death rates and the change of the suicide seasonality in Taiwan during
      1991-2008. The monthly suicide death rates of the total, male and female
      populations during January 1991-December 2008 were obtained from a population
      based database. There was an upward trend. The means of the monthly suicide rates
      after adjusting the calendar effect and the upward trend were compared. The
      suicide data were further analysed in three 6-year periods to explore the change
      of seasonality. During 1991-2008 in Taiwan, suicide rates had significant peaks
      in April and May, and nadirs in January and December. The monthly distributions
      varied during 1991-1996, 1997-2002 and 2003-2008 in the patterns and the
      statistical significance. There was no linear trend for the change of the
      seasonality of suicide death rate.

PMID- 20801526
TI  - Molecular cloning of IgT from Atlantic salmon, and analysis of the relative
      expression of tau, MU, and delta in different tissues.
AB  - In the present study, IgT genes of Atlantic salmon were cloned and characterised.
      Analysis of our sequence data as well as ESTs reported to the databases revealed
      three distinct IgT heavy chain sub-variants in salmon, as opposed to two of IgM
      and IgD. The IgT sub-variants in salmon are 76-80% identical to each other, and
      75-82% identical to the reported rainbow trout sequences, whereas the similarity
      to the orthologous molecules in zebrafish, grass carp, mandarin fish, and grouper
      is 25-41%. The heavy chains of both secreted and membrane anchored forms of
      salmon IgT include four constant Ig domains, tau1-tau4. This parallels the IgM
      heavy chains in elasmobranch fish and higher vertebrates, but differs from IgM in
      teleost fish where the membrane anchored form include only three constant Ig
      domains, MU1-MU3. The similarity between tau1 and MU1 in salmon is relatively
      high (52%) when compared to the remaining part of the molecules (tau2-tau4 and
      MU2-MU4 are 13-24% similar). To compare tau, MU and delta expressions in
      different tissues (head kidney, thymus, spleen, gill, skin, hind gut, brain and
      muscle) of Atlantic salmon, RT-qPCR assays were designed and evaluated. The
      analyses revealed that IgM transcripts are most abundant (up to 200 times more
      than IgD) followed by IgT (up to 20 times more than IgD) in most tissues. Highest
      expression of IgM, IgT, and IgD was in head kidney and spleen.

PMID- 20801527
TI  - Differential induction of Toll-like receptor gene expression in equine monocytes
      activated by Toll-like receptor ligands or TNF-alpha.
AB  - Toll-like receptors (TLRs) function as sentinels for the innate immune system,
      detecting microbial ligands during infection and inflammation. Previous studies
      indicate that activation of these receptors on equine monocytes leads to discrete
      pro- and anti-inflammatory responses that are mediated through the induction of
      specific cytokine genes. However, less is known regarding the regulation of TLR
      gene expression in these cells. Therefore, we investigated the effects of ligands
      recognized by TLR2, 3 or 4 upon TLR2, 3 and 4 gene expression by equine
      monocytes. We determined that incubation of monocytes with TLR2 and 4 ligands,
      which signal through the intracellular adaptor protein MyD88, induces expression
      of the TLR2 and 4 genes, but not the TLR3 gene. Conversely, incubation with a
      TLR3 ligand, which recruits the TRIF adaptor protein, selectively induces
      expression of the TLR3 gene, but not TLR2 or 4 genes. Furthermore, incubation of
      these cells with TNF-alpha, the pro-inflammatory cytokine that is a hallmark of
      TLR activation, does not affect expression of the three TLR genes. These findings
      suggest that exposure of equine monocytes to microbial ligands but not to
      endogenous inflammatory mediators may initiate responses that alter the horse's
      sensitivity to other microbial components during infections.

PMID- 20801528
TI  - Photoreceptor cells constitutively express functional TLR4.
AB  - Toll-like receptor 4 (TLR4) is expressed on a number of cells including neurons
      in the brain. However, it has yet to be determined if TLR4 is expressed on
      photoreceptor cells in the retina. In this report, we examined primary
      photoreceptor cells and an established photoreceptor cell line (661W). We found
      that functional TLR4 is constitutively expressed on photoreceptor cells, and can
      be activated by LPS. We conclude that TLR4 on photoreceptor cells could directly
      contribute to retinal inflammatory diseases and photoreceptor cell survival.

PMID- 20801529
TI  - Recent advances in the development of antimuscarinic agents for overactive
      bladder.
AB  - Pharmacologic therapies (primarily antimuscarinic agents) have been the mainstay
      of treatment for overactive bladder. In their traditional forms, these drugs
      produce variable efficacy, a moderate prevalence of side effects, and rare
      occurrences of cure. The search for newer and better formulations and derivatives
      of this class of medication (as well as novel therapies) is ongoing, fueled
      primarily by the high prevalence of overactive bladder and the tremendous number
      of healthcare dollars spent on current therapy. In the present article, we
      discuss recent advances in the development of new antimuscarinic agents,
      important progress in understanding the mechanism of action of this class of
      drug, and the impact these developments have had on clinical practice.

PMID- 20801530
TI  - Pain, physical performance and balance in the elderly at hospital.
AB  - This study was aimed to determine the pain, physical performance and balance
      conditions of the elderly hospitalized in university hospital geriatric wards.
      The reasons for hospitalization and co-morbid diseases were recorded. Severity of
      pain was assessed on a visual analogue scale. Activity independence ability was
      tested by physical performance test (PPT). Tinetti balance and gait evaluation
      scale (GES) were used to assess balance. Fifty patients (54%) had reported any
      kind of pain. Mean score for PPT was 13.32 +/- 6.56 and for Tinetti test was 9.76
      +/- 3.8. The correlation between pain, physical performance and balance for 93
      patients, 65 years and above was analyzed and not found statistically
      significant. We believe that pain can affect physical performance and balance.
      Therefore, it should be carefully evaluated in every elderly patient. Further
      studies are necessary to investigate the relationship between pain, physical
      performance and balance of elderly hospitalized patients.

PMID- 20801531
TI  - Impact of nutritional status on long-term functional outcomes of post-acute
      stroke patients in Taiwan.
AB  - Nutritional status is important in stroke care, but little is known regarding to
      the prognostic role of nutritional status on long-term functional outcomes among
      stroke survivors. The main purpose of this study was to evaluate to the
      prognostic role of nutritional status on long-term functional outcomes among
      stroke survivors. Data of acute stroke registry in Kaohsiung Veterans General
      Hospital were retrieved for analysis. Overall, 483 patients (mean age = 70.7 +/-
      10.3 years) with first-ever stroke were found. Among them, 95 patients (19.7%)
      were malnourished at admission, 310 (mean age = 70.4 +/- 10.1 years, 63.5% males)
      survived for 6 months, and 244 (78.7%) had good functional outcomes. Subjects
      with poor functional outcomes were older (74.7 +/- 8.9 vs. 69.0 +/- 10.1 years, p
      < 0.001), more likely to be malnourished (56.2% vs. 26.6%, p < 0.001), to develop
      pneumonia upon admission (23.3% vs. 12.7%, p = 0.027), had a longer hospital stay
      (23.5 +/- 13.9 vs. 12.5 +/- 8.2 days, p < 0.001), had a higher National
      Institutes of Health Stroke Scale (NIHSS) score (12.9 +/- 9.3 vs. 4.9 +/- 4.3, p
      < 0.001), poorer stroke recovery (NIHSS improvement: 6.9% vs. 27.4%, p = 0.005),
      and poorer functional improvement (Barthel index = BI improvement in the first
      month: 31.4% vs. 138%, p < 0.001). Older age (odds ratio = OR) = 1.07, 95%
      confidence interval (CI = 1.03-1.11, p<0.001), baseline NIHSS score (OR = 1.23,
      95%CI = 1.15-1.31, p < 0.001) and malnutrition at acute stroke (OR = 2.57, 95%CI:
      1.29-5.13, p<0.001) were all independent risk factors for poorer functional
      outcomes. In conclusion, as a potentially modifiable factor, more attentions
      should be paid to malnutrition to promote quality of stroke care since the acute
      stage.

PMID- 20801532
TI  - Analysis of the Z-disc genes PDLIM3 and MYPN in patients with hypertrophic
      cardiomyopathy.

PMID- 20801533
TI  - The cost of different types of lameness in dairy cows calculated by dynamic
      programming.
AB  - Traditionally, studies which placed a monetary value on the effect of lameness
      have calculated the costs at the herd level and rarely have they been specific to
      different types of lameness. These costs which have been calculated from former
      studies are not particularly useful for farmers in making economically optimal
      decisions depending on individual cow characteristics. The objective of this
      study was to calculate the cost of different types of lameness at the individual
      cow level and thereby identify the optimal management decision for each of three
      representative lameness diagnoses. This model would provide a more informed
      decision making process in lameness management for maximal economic
      profitability. We made modifications to an existing dynamic optimization and
      simulation model, studying the effects of various factors (incidence of lameness,
      milk loss, pregnancy rate and treatment cost) on the cost of different types of
      lameness. The average cost per case (US$) of sole ulcer, digital dermatitis and
      foot rot were 216.07, 132.96 and 120.70, respectively. It was recommended that
      97.3% of foot rot cases, 95.5% of digital dermatitis cases and 92.3% of sole
      ulcer cases be treated. The main contributor to the total cost per case of sole
      ulcer was milk loss (38%), treatment cost for digital dermatitis (42%) and the
      effect of decreased fertility for foot rot (50%). This model affords versatility
      as it allows for parameters such as production costs, economic values and disease
      frequencies to be altered. Therefore, cost estimates are the direct outcome of
      the farm specific parameters entered into the model. Thus, this model can provide
      farmers economically optimal guidelines specific to their individual cows
      suffering from different types of lameness.

PMID- 20801534
TI  - A cohort study of post-weaning multisystemic wasting syndrome and PCV2 in 178
      pigs from birth to 14 weeks on a single farm in England.
AB  - Our hypothesis was that pigs that develop post-weaning multisystemic wasting
      syndrome (PMWS) are detectable from an early age with signs of weight loss and
      other clinical and serological abnormalities. Therefore, the objective of this
      study was to investigate the temporally varying and fixed events linked with the
      clinical incidence of PMWS by comparing affected and unaffected pigs in a cohort
      of 178 male piglets. Piglets were enrolled at birth and examined each week.
      Samples of blood were collected at regular intervals. The exposures measured were
      porcine circovirus type 2 (PCV2) antibody titres in all 178 and PCV2 antigen in a
      subset of 75 piglets. We also observed piglet health and measured their weight,
      and a post-mortem examination was performed by an external laboratory on all pigs
      between 6 and 14 weeks of age that died. From the cohort, 14 (8%) pigs died from
      PMWS and 4% from other causes. A further 37 pigs between 6 and 14 weeks of age
      died from PMWS (30) and ileitis and other causes (7). PMWS was only apparent in
      pigs from 1 to 2 weeks before death when they wasted rapidly. There were no other
      characteristic clinical signs and no obvious gross clinical lesions post-mortem.
      There was no strong link with PCV2 antibody throughout life but PCV2 antigen
      level was higher from 4 to 6 weeks of age in pigs that died from PMWS compared
      with pigs that died from other causes.

PMID- 20801535
TI  - Detection and characterization of infectious bursal disease viruses in broilers
      at processing.
AB  - The presence of infectious bursal disease virus (IBDV) in broilers entering
      processing plants was examined. The dissemination of IBDV and the introduction of
      non-native strains for example very virulent (vv) IBDV have had a negative
      economic impact on poultry production in many countries. Restrictions have been
      placed on the import and export of poultry products by some countries. There is a
      perceived risk that IBDV can be spread through transportation and contamination
      of processing equipment, poultry protein products and processing plant personnel.
      This risk, however, is fundamentally unknown because scientific studies have not
      been conducted on the presence of IBDV in birds entering processing plants or the
      variables that may affect this risk during and post-harvest. The goal of this
      study was to determine if infectious IBDV was present in broilers entering
      processing plants. A total of 47 pooled bursa samples from 26 processing plants
      in the Eastern U.S. were examined. Molecular testing indicated that an IBDV
      specific RT-PCR was positive in 12 (25.5%) of the samples from 11 different
      processing plants. Nucleotide sequence analysis was conducted on the 12 RT-PCR
      positive samples and indicated the IBDV was not commercially available attenuated
      vaccine strains. Most of the sequences were unique and a phylogenic analysis
      indicated they were most closely related to variant strains of IBDV. Five RT-PCR
      positive samples were selected at random for testing in specific-pathogen-free
      chickens. All five samples contained infectious IBDV as evidenced by macroscopic
      lesions and bursa/body weight ratios that were significantly lower in infected
      birds than in the non-inoculated controls. The five viruses were re-identified in
      bursa tissue from chickens in their respective groups at necropsy using RT-PCR
      and nucleotide sequencing. The results indicate that infectious and pathogenic
      IBDV are entering processing plants in this geographic region of the U.S.
      Additional studies are needed on post-harvest variables that could increase or
      decrease the risk that these viruses are being disseminated during this process.

PMID- 20801536
TI  - Lactobacilli as multifaceted probiotics with poorly disclosed molecular
      mechanisms.
AB  - Lactic acid bacteria and more particularly lactobacilli have been used for the
      production of fermented foods for centuries. Several lactobacilli have been
      recognized as probiotics due to their wide range of health-promoting effects in
      humans. However, little is known about the molecular mechanisms underpinning
      their probiotic functions. Here we reviewed the main beneficial effects of
      lactobacilli and discussed, when the information is available, the molecular
      machinery involved in their probiotic function. Among the beneficial effects,
      lactobacilli can improve digestion, absorption and availability of nutrients. As
      an example, some strains are able to degrade carbohydrates such as lactose or
      alpha-galactosides that may cause abdominal pain. Furthermore, they can hydrolyze
      compounds that limit the bioavailability of minerals like tannin and phytate due
      to tannin acylhydrolase and phytase activities. In addition, it was shown that
      some lactobacilli strains can improve mineral absorption in Caco-2 cells.
      Lactobacilli can also contribute to improve the nutritional status of the host by
      producing B group vitamins. More recently, the role of lactobacilli in energy
      homeostasis, particularly in obese patients, is the object of an increased
      interest. Lactobacilli are also involved in the prevention of diseases. They have
      potential to prevent carcinogenesis through the modulation of enzymes involved in
      the xenobiotic pathway, and may prevent cardiovascular diseases such as
      hypertension through the production of a bioactive peptide that may have
      angiotensin converting enzyme inhibitor activity. Lactobacilli are increasingly
      studied for the treatment of inflammatory bowel diseases and exhibit interesting
      potential in the reduction of pain perception. The ability of some strains to
      bind to intestinal cells, their pathogen-associated molecular patterns and the
      metabolites they produce confer interesting immunomodulatory effects. Finally,
      pathogenic fungi, virus or bacteria can be inhibited by probiotics. They can
      reinforce the intestinal barrier, simply occupying the ecological niche, or they
      can have an active role by synthesizing various metabolites inhibiting pathogen
      development. Lactobacilli have a long standing history with foods and humans but
      comparatively, their history as probiotics is recent. Their effects are
      investigated in in vitro and in vivo models leading sometimes to contradictory or
      controversial results that make necessary final demonstrations through clinical
      trials. Researches on molecular mechanisms involved in the beneficial effects
      reviewed here are necessary for a better understanding of these effects, but
      could also lead to the development of molecular tools to help the screening of
      the probiotic potential of lactobacilli that are common inhabitants of numerous
      fermented foods around the world.

PMID- 20801537
TI  - Hepatitis C virus NS2 protein triggers endoplasmic reticulum stress and
      suppresses its own viral replication.
AB  - BACKGROUND & AIMS: We previously reported that the NS2 protein of hepatitis C
      virus (HCV) inhibits the expression of reporter genes driven by a variety of
      cellular and viral promoters. The aim of the study was to determine whether the
      broad transcriptional repression is caused by endoplasmic reticulum (ER) stress.
      METHODS: Phosphorylation of the translation initiation factor eIF2alpha and HCV
      replication was detected by Western and Northern blot, respectively. De novo
      protein synthesis was measured by metabolic labeling. Activation of ER stress
      responsive genes was determined by promoter reporter assay, as well as mRNA and
      protein measurement by real time PCR and Western blot. RESULTS: Transient or
      inducible NS2 protein expression increased eIF2alpha phosphorylation and reduced
      de novo protein synthesis. It up-regulated promoter activities and transcript
      levels of ER stress inducible genes including GRP78, ATF6, and GADD153, as well
      as GRP78 protein level. The same effect was observed when NS2 was synthesized as
      part of the core-E1-E2-p7-NS2 polypeptide. NS2 protein also inhibited reporter
      gene expression from the HCV internal ribosome entry site and consequently
      reduced HCV replication. The full-length HCV replicon activated GRP78, ATF6, and
      GADD153 promoters more efficiently than the subgenomic replicon lacking the
      coding sequence for both the structural proteins and NS2. Abrogation of HCV
      infection/replication, by an inhibitor of the NS3 protease, relieved ER stress.
      CONCLUSIONS: HCV infection can induce ER stress, with NS2 protein being a major
      mediator. The stress can be relieved by a feedback mechanism.

PMID- 20801538
TI  - The SV2 variant of KLF6 is down-regulated in hepatocellular carcinoma and
      displays anti-proliferative and pro-apoptotic functions.
AB  - BACKGROUND & AIMS: KLF6 protein is a transcription factor that plays important
      functions in hepatocellular carcinoma (HCC), which is one of the leading causes
      of death by cancer worldwide. Previous studies showed the existence of three
      splice variants of KLF6, termed SV1, SV2, and SV3. An increased SV1/KLF6 mRNA
      ratio in HCC was already described. In this study, we aimed to investigate the
      expression of the SV2 variant in HCC samples and its role in hepatic cells.
      METHODS: We measured the expression of the SV2 variant in HCC and adjacent tissue
      samples by q-RT-PCR. We established IHH and HepG2 stable cell lines over
      expressing the SV2 variant and measured cell growth and apoptotic rate. RESULTS:
      We observed a reduced expression of the SV2 variant in HCC samples versus
      surrounding tissues and normal liver. Interestingly, our findings demonstrate
      that the over-expression of the SV2 variant in IHH and HepG2 cells leads to a
      significant reduction of proliferation associated with cell death by apoptosis.
      We further demonstrate that the SV2 expression leads to an induction of the cell
      cycle-controlling p21(CIP/WAF1) and the pro-apoptotic Bax genes, mediated by the
      p53 protein. We show further that the SV2 expression in IHH and HepG2 cells
      induces their sensitivity to the anti-cancer drug, gemcitabine. CONCLUSION: We
      reveal a reduced expression of the SV2 variant of KLF6 in HCC samples and
      describe anti-proliferative and pro-apoptotic functions for this variant in
      hepatic cells.

PMID- 20801539
TI  - Hepatitis C virus entry and glucocorticosteroids.

PMID- 20801541
TI  - Assessment of liver fibrosis with transient elastography and FibroTest in
      patients treated with methotrexate for chronic inflammatory diseases: a case
      control study.
AB  - BACKGROUND & AIMS: Although methotrexate (MTX) is used in the effective treatment
      of inflammatory disorders, its use is hampered by the risk of liver fibrosis. Non
      invasive methods for the diagnosis of liver fibrosis, such as transient
      elastography (FibroScan) and FibroTest could be useful for monitoring MTX-liver
      toxicity. The aim of this case-control study was to determine factors associated
      with liver fibrosis in a large cohort of patients requiring MTX. METHODS:
      Consecutive adults with various benign inflammatory diseases were prospectively
      assessed using FibroScan and FibroTest when they were treated with MTX (cases) or
      before beginning treatment (controls). RESULTS: Among 518 included patients, 44
      patients (8.5%) had FibroScan and/or FibroTest results suggesting severe liver
      fibrosis. In a multivariate analysis, factors associated with abnormal markers of
      liver fibrosis were the body mass index >28 kg/m(2) and high alcohol consumption.
      Neither long MTX duration nor cumulative doses were associated with elevated
      FibroScan or FibroTest results. CONCLUSIONS: Severe liver fibrosis is a rare
      event in patients treated with MTX and is probably unrelated to the total dose.
      Patients with other risk factors for liver disease should be closely monitored
      with non-invasive methods before and during MTX treatment.

PMID- 20801540
TI  - Hepatic but not brain iron is rapidly chelated by deferasirox in
      aceruloplasminemia due to a novel gene mutation.
AB  - BACKGROUND & AIMS: Aceruloplasminemia is a rare autosomal recessive
      neurodegenerative disease associated with brain and liver iron accumulation which
      typically presents with movement disorders, retinal degeneration, and diabetes
      mellitus. Ceruloplasmin is a multi-copper ferroxidase that is secreted into
      plasma and facilitates cellular iron export and iron binding to transferrin.
      RESULTS: A novel homozygous ceruloplasmin gene mutation, c.2554+1G>T, was
      identified as the cause of aceruloplasminemia in three affected siblings. Two
      siblings presented with movement disorders and diabetes. Complementary DNA
      sequencing showed that this mutation causes skipping of exon 14 and deletion of
      amino acids 809-852 while preserving the open reading frame. Western blotting of
      liver extracts and sera of affected patients showed retention of the abnormal
      protein in the liver. Aceruloplasminemia was associated with severe brain and
      liver iron overload, where hepatic mRNA expression of the iron hormone hepcidin
      was increased, corresponding to the degree of iron overload. Hepatic iron
      concentration normalized after 3 and 5months of iron chelation therapy with
      deferasirox, which was also associated with reduced insulin demands. During short
      term treatment there was no clinical or imaging evidence for significant effects
      on brain iron overload. CONCLUSIONS: Aceruloplasminemia can show an incomplete
      clinical penetrance but is invariably associated with iron accumulation in the
      liver and in the brain. Iron accumulation in aceruloplasminemia is a result of
      defective cellular iron export, where hepcidin regulation is appropriate for the
      degree of iron overload. Iron chelation with deferasirox was effective in
      mobilizing hepatic iron but has no effect on brain iron.

PMID- 20801542
TI  - Enteral nutrition with or without N-acetylcysteine in the treatment of severe
      acute alcoholic hepatitis: a randomized multicenter controlled trial.
AB  - BACKGROUND & AIMS: Severe acute alcoholic hepatitis is associated with a high
      mortality rate. Oxidative stress is involved in the pathogenesis of acute
      alcoholic hepatitis. Previous findings had also suggested that enteral
      nutritional support might increase survival in patients with severe acute
      alcoholic hepatitis. Therefore, the aim of the present study was to evaluate the
      efficacy of N-acetylcysteine in combination with adequate nutritional support in
      patients with severe acute alcoholic hepatitis. METHODS: Patients with biopsy
      proven acute alcoholic hepatitis and mDF >=32 were randomized to receive N
      acetylcysteine intravenously or a placebo perfusion along with adequate
      nutritional support for 14 days. The primary endpoint was 6-month survival;
      secondary endpoints were biological parameter evolution and infection rate.
      RESULTS: Fifty-two patients were randomized in the study (28 into the N
      acetylcysteine arm, 24 into the control arm), and among them, five were excluded
      from the analysis for protocol violation. The two groups did not differ in
      baseline characteristics. Survival rates at 1 and 6 months in N-acetylcysteine
      and control groups were 70.2 vs. 83.8% (p=0.26) and 62.4 vs. 67.1% (p=0.60),
      respectively. Early biological changes, documented infection rate at 1 month, and
      incidence of hepatorenal syndrome did not differ between the two groups.
      CONCLUSIONS: In this study, high doses of intravenous N-acetylcysteine therapy
      for 14 days conferred neither survival benefits nor early biological improvement
      in severe acute alcoholic hepatitis patients with adequate nutritional support.
      However, these results must be viewed with caution, since the study suffered from
      a lack of power.

PMID- 20801543
TI  - Impact of glucocorticoids on insulin resistance in the critically ill.
AB  - Glucocorticoids (GCs) have been shown to reduce insulin sensitivity in healthy
      individuals. Widely used in critical care to treat a variety of inflammatory and
      allergic disorders, they may inadvertently exacerbate stress-hyperglycaemia. This
      research uses model-based methods to quantify the reduction in insulin
      sensitivity from GCs in critically ill patients, and thus their impact on
      glycaemic control. A model-based measure of insulin sensitivity (S(I)) was used
      to quantify changes between two matched cohorts of 40 intensive care unit (ICU)
      patients. Patients in one cohort received GC treatment, while patients in the
      control cohort did not. All patients were admitted to the Christchurch hospital
      ICU between 2005 and 2007 and spent at least 24h on the SPRINT glycaemic control
      protocol. A 31% reduction in whole-cohort median insulin sensitivity was seen
      between the control cohort and patients receiving glucocorticoids with a median
      dose equivalent to 200mg/d of hydrocortisone per patient. Comparing percentile
      patients as a surrogate for matched patients, reductions in median insulin
      sensitivity of 20%, 25%, and 21% were observed for the 25th-, 50th- and 75th
      percentile patients, respectively. These cohort and percentile patient reductions
      are less than or equivalent to the 30-62% reductions reported in healthy subjects
      especially when considering the fact that the GC doses in this study are 1.3-4.0
      times larger than those in studies of healthy subjects. This reduced suppression
      of insulin sensitivity in critically ill patients could be a result of saturation
      due to already increased levels of catecholamines and cortisol common in
      critically illness. Virtual trial simulation showed that reductions in insulin
      sensitivity of 20-30% associated with glucocorticoid treatment in the ICU have
      limited impact on glycaemic control levels within the context of the SPRINT
      protocol.

PMID- 20801544
TI  - Inoperable early stage non-small cell lung cancer: comorbidity, patterns of care
      and survival.
AB  - PURPOSE: To evaluate comorbidities, patterns of care and outcomes for patients
      with inoperable stage I and II non-small cell lung cancer (NSCLC). MATERIALS AND
      METHODS: Patients diagnosed with stage I or II NSCLC in British Columbia between
      1996 and 2005 who did not undergo primary surgery and were referred for oncology
      assessment were identified in a retrospective analysis. Baseline comorbidity and
      pulmonary function data for patients treated with curative radiotherapy (CurRT;
      biologically effective dose [BED]>58 Gy(10)) were abstracted by chart review.
      Kaplan-Meier and Cox regression were used to determine factors associated with
      overall survival (OS) and cause-specific survival (CSS) based on treatment group
      [no radiotherapy (NoRT), palliative radiotherapy (PallRT), or CurRT]. RESULTS: Of
      1043 patients identified, approximately 1/3 received CurRT, and these patients
      had better performance status and lower stage disease than the other groups.
      There was a high prevalence of comorbid conditions in the CurRT group; 90% of
      CurRT patients had an age-adjusted Charlson comorbidity index (CCI) score >=5.
      CurRT patients had a median survival 1-year longer than patients treated with
      PallRT or NoRT (p < 0.0001). In CurRT patients, CCI was predictive of OS (HR 1.1
      per point CCI increase; p = 0.044), but not CSS. Patients receiving PallRT with a
      BED > 50 Gy(10) had significantly longer OS than those receiving PallRT of <=50
      Gy(10) (p < 0.0001). CONCLUSIONS: Treatment of medically inoperable early stage
      NSCLC patients with CurRT is associated with a significantly longer survival, and
      for these patients CCI is a significant predictor of OS. For patients treated
      with PallRT, higher doses of palliative thoracic RT is associated with improved
      OS.

PMID- 20801545
TI  - Macrophage podosomes go 3D.
AB  - Macrophage tissue infiltration is a critical step in the immune response against
      microorganisms and is also associated with disease progression in chronic
      inflammation and cancer. Macrophages are constitutively equipped with specialized
      structures called podosomes dedicated to extracellular matrix (ECM) degradation.
      We recently reported that these structures play a critical role in trans-matrix
      mesenchymal migration mode, a protease-dependent mechanism. Podosome molecular
      components and their ECM-degrading activity have been extensively studied in two
      dimensions (2D), but yet very little is known about their fate in three
      dimensional (3D) environments. Therefore, localization of podosome markers and
      proteolytic activity were carefully examined in human macrophages performing
      mesenchymal migration. Using our gelled collagen I 3D matrix model to obligate
      human macrophages to perform mesenchymal migration, classical podosome markers
      including talin, paxillin, vinculin, gelsolin, cortactin were found to accumulate
      at the tip of F-actin-rich cell protrusions together with beta1 integrin and CD44
      but not beta2 integrin. Macrophage proteolytic activity was observed at podosome
      like protrusion sites using confocal fluorescence microscopy and electron
      microscopy. The formation of migration tunnels by macrophages inside the matrix
      was accomplished by degradation, engulfment and mechanic compaction of the
      matrix. In addition, videomicroscopy revealed that 3D F-actin-rich protrusions of
      migrating macrophages were as dynamic as their 2D counterparts. Overall, the
      specifications of 3D podosomes resembled those of 2D podosome rosettes rather
      than those of individual podosomes. This observation was further supported by the
      aspect of 3D podosomes in fibroblasts expressing Hck, a master regulator of
      podosome rosettes in macrophages. In conclusion, human macrophage podosomes go 3D
      and take the shape of spherical podosome rosettes when the cells perform
      mesenchymal migration. This work sets the scene for future studies of molecular
      and cellular processes regulating macrophage trans-migration.

PMID- 20801546
TI  - Characterization of the Medicago truncatula cell wall proteome in cell suspension
      culture upon elicitation and suppression of plant defense.
AB  - In addition to establishing methods for proteome analysis of cell wall proteins
      (CWPs) for the model plant Medicago truncatula, this work highlights the presence
      of several protein classes in cell culture. Using a combination of two
      dimensional gel electrophoresis (2D-PAGE) and/or liquid chromatography-tandem
      mass spectrometry (LC-MS/MS), we established the proteome reference map of M.
      truncatula cell wall proteins. CWPs extracted from purified cell wall fragments
      resulted in the identification of 46 (2D-PAGE) and 65 (LC-MS/MS) proteins,
      respectively, with a total of 111 proteins. The identified proteins are involved
      in various processes, including cell wall modifications, signaling, defense
      mechanisms, membrane transport, protein synthesis and processing. Further, we
      conducted comparative proteome analysis to identify changes in protein
      composition during interaction of M. truncatula cell suspension culture with a
      pathogen-derived yeast elicitor (YE) and suppressor using Sinorhizobium meliloti
      LPS. 2D-PAGE analysis for the CWPs after YE and LPS treatment resembled the
      proteome map of YE alone, with a few up-regulated proteins involved in defense,
      and in the case of the LPS-treated cell wall proteome, there was no significant
      difference observed. Using this approach, proteins involved in defense, such as l
      ascorbate peroxidase, specifically targeted proteins to the cell wall during
      defense, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and proteins
      that play an important role during growth and development were identified. Also,
      some defense-related proteins were absent in the same gel after YE treatment,
      suggesting that oxidant protection is regulated by these proteins.

PMID- 20801547
TI  - Genetic stability analysis of chrysanthemum (Chrysanthemum x morifolium Ramat)
      after different stages of an encapsulation-dehydration cryopreservation protocol.
AB  - Genetic stability in chrysanthemum (cultivar 'Pasodoble') apices was studied at
      each step of an encapsulation-dehydration cryopreservation protocol: control
      shoots (A), nodal segments after cold treatment (N), apices after osmotic stress
      (0.3M sucrose) and cold treatment (P), encapsulation and culture in 0.8M sucrose
      (S), dehydration (D), and cryopreservation (Cr). Two different markers were
      employed: RAPDs and AFLPs. Throughout the process, the origin of the apices (in
      vitro shoot from which they were excised) was recorded. Eight complete lines
      (from which DNA could be amplified after all the steps considered) were studied.
      Two out of twelve arbitrary primers showed polymorphisms. Three RAPD markers were
      replaced by three new ones in the Cr sample in one line. Using a different
      primer, a 700bp fragment was absent from all samples from the 0.3M sucrose
      culture step ('P') onwards, in all the lines studied. The sequences of these
      fragments were studied to find similarities with known sequences. Polymorphic
      AFLP fragments were also observed, and most of the differences appeared from step
      'P' onwards, pointing out the possible effect of this process (preculture on 0.3M
      sucrose) in the DNA variation. These results show that genetic variation can
      appear throughout the cryopreservation process, and the low temperature itself is
      not the only stress risk of the technique. Therefore, genetic stability of the
      regenerants obtained after cryopreservation should be monitored.

PMID- 20801548
TI  - Mycorrhizal fungi symbiosis as a strategy against oxidative stress in soybean
      plants.
AB  - Oxidative stress responses generated by paraquat (PQ), an herbicide that triggers
      an oxidative stress reaction in leaves, were studied in non-arbuscular
      mycorrhizal (non-AM) and in arbuscular mycorrhizal (AM) soybean plants inoculated
      with Glomus mosseae (Gm) or Glomus intraradices (Gi). Some oxidative stress
      symptoms were evident in non-AM after 6 d of PQ application on leaves. Oxidative
      damage, measured as malondialdehyde content (MDA), was significantly higher, and
      although no changes were evident in total catalase (CAT, EC 1.11.1.6) and total
      superoxide dismutase (SOD, EC 1.15.1.1) activity, total ascorbate peroxidase
      (APX, EC 1.11.1.11) activity was significantly reduced. These effects were
      correlated with a significant decrease in growth parameters. By contrast, in both
      AM plants, foliar MDA content was reduced or unaltered and, interestingly, after
      PQ stress, its level was unchanged and significantly lower than in PQ non-AM
      plants. Unlike PQ stress in non-AM plants, total APX activity was unaltered or
      induced by AM plants, while total SOD activity was unchanged and no consistent
      effects were detected in total CAT activity. All these events coincided with no
      changes or a significant increase in growth parameters. Since oxidative stress is
      a common phenomenon triggered by several environmental stresses, these results
      highlight the importance of mycorrhizal fungi in oxidative stress regulation as a
      general strategy to protect plants from abiotic and biotic stress.

PMID- 20801550
TI  - Synthesis, characterization, oxidative degradation, antibacterial activity and
      acetylcholinesterase/butyrylcholinesterase inhibitory effects of some new
      phosphorus(V) hydrazides.
AB  - Some new phosphorus(V) hydrazides 1a-12a were synthesized and characterized by
      (1)H, (13)C, (31)P NMR, IR spectroscopy and elemental analysis. Moreover, the
      interaction of Cu(M)(2).nH(2)O with 1a, 3a and 7a gave 4,4'
      bis(morpholine)diazene (1b). In fact, in these reactions, copper(II) ions acted
      as oxidizing agent. The results supported the proposed mechanism. The structures
      of compounds 1a, 1b and 1c were further determined by X-ray crystallography.
      Compounds 1a-12a were screened for their antibacterial activities. Also, the
      acetyl- and butyrylcholinesterase inhibitory activity of 1a, 3a, 7a, 11a and 12a
      was measured using Ellman's method. It is interesting that these compounds were
      more potent inhibitors of BChE than of AChE. Also, using Lineweaver-Burk plots,
      it was indicated these compounds are mixed inhibitors.

PMID- 20801549
TI  - Age-related effects on cortical thickness patterns of the Rhesus monkey brain.
AB  - The Rhesus monkey is a useful model for examining age-related as well as other
      neurological and developmental effects on the brain, because of the extensive
      neuroanatomical homology to the human brain, the reduced occurrence of
      neurological diseases such as Alzheimer's disease, and the possibility of
      obtaining relevant behavioral data and post-mortem tissue for histological
      analyses. In this study, cortical thickness measurements based on a cortical
      surface modeling technique were applied for the first time to investigate
      cortical thickness patterns in the rhesus monkey brain, and were used to evaluate
      regional age related effects across a wide range of ages. Age related effects
      were observed in several cortical areas, in particular in the somato-sensory and
      motor cortices, where a robust negative correlation of cortical thickness with
      age was observed, similar to that found in humans. In contrast, results for
      monkeys compared with humans show significant interspecies differences in
      cortical thickness patterns in the frontal and the inferior temporal regions.

PMID- 20801551
TI  - Synthesis and evaluation of novel stearoyl-CoA desaturase 1 inhibitors: 1'-{6-[5
      (pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-3,4
      dihydrospiro[chromene-2,4'-piperidine] analogs.
AB  - In continuation of our investigation on novel stearoyl-CoA desaturase (SCD) 1
      inhibitors, we have already reported on the structural modification of the
      benzoylpiperidines that led to a series of novel and highly potent
      spiropiperidine-based SCD1 inhibitors. In this report, we would like to extend
      the scope of our previous investigation and disclose details of the synthesis,
      SAR, ADME, PK, and pharmacological evaluation of the spiropiperidines with high
      potency for SCD1 inhibition. Our current efforts have culminated in the
      identification of 5-fluoro-1'-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2
      yl]pyridazin-3-yl}-3,4-dihydrospiro[chromene-2,4'-piperidine] (10e), which
      demonstrated a very strong potency for liver SCD1 inhibition (ID(50)=0.6 mg/kg).
      This highly efficacious inhibition is presumed to be the result of a combination
      of strong enzymatic inhibitory activity (IC(50) (mouse)=2 nM) and good oral
      bioavailability (F >95%). Pharmacological evaluation of 10e has demonstrated
      potent, dose-dependent reduction of the plasma desaturation index in C57BL/6J
      mice on a high carbohydrate diet after a 7-day oral administration (q.d.). In
      addition, it did not cause any noticeable skin abnormalities up to the highest
      dose (10 mg/kg).

PMID- 20801552
TI  - Therapeutic potential of sulindac hydroxamic acid against human pancreatic and
      colonic cancer cells.
AB  - The non-steroidal anti-inflammatory drug (NSAID) sulindac exhibits cyclooxygenase
      (COX)-dependent and COX-independent chemopreventive properties in human cancer.
      The present study was aimed at investigating whether the hydroxamic acid
      substitution for the carboxylic acid group could enhance the in vitro antitumor
      and antiangiogenic activities of sulindac. Characterization tools used on this
      study included analyses of cell viability, caspase 3/7 induction, DNA
      fragmentation, and gene expression. Our findings demonstrate that the newly
      synthesized hydroxamic acid derivative of sulindac and its sulfone and sulfide
      metabolites were characterized by a good anticancer activity on human pancreatic
      and colon cancer cells, both in terms of potency (IC(50) mean values from 6 +/-
      1.1 MUM to 64 +/- 1.1 MUM) and efficacy (E(max) of ~100%). Hydroxamic acid
      derivatives trigger a higher degree of apoptosis than carboxylic acid
      counterparts, increase bax/bcl-2 expression ratio and induce caspase 3/7
      activation. Most notably, these compounds significantly inhibit proangiogenic
      growth factor-stimulated proliferation of vascular endothelial cell (HUVEC) at
      sub-micromolar concentrations. Our data also provide evidence that the COX-active
      metabolite of sulindac hydroxamic acid were the most active of the series and
      selective inhibition of COX-1 but not COX-2 can mimic its effects, suggesting
      that COX inhibition could only play a partial role in the mechanism of compound
      action. In conclusion, these data demonstrate that substitution of the carboxylic
      acid group with the hydroxamic acid moiety enhances in vitro antiproliferative,
      proapoptotic and antiangiogenic properties of sulindac, therefore increasing the
      therapeutic potential of this drug.

PMID- 20801553
TI  - Synthesis, antimicrobial and anti-inflammatory activities of novel 5-(1
      adamantyl)-1,3,4-thiadiazole derivatives.
AB  - New 1-adamanyl-1,3,4-thiadiazole derivatives namely, 5-(1-adamantyl)-1,3,4
      thiadiazoline-2-thione 3, 5-(1-adamantyl)-3-(benzyl- or 4-substituted benzyl)
      1,3,4-thiadiazoline-2-thione 4a-d, 5-(1-adamantyl)-3-(4-substituted-1
      piperazinylmethyl)-1,3,4-thiadiazoline-2-thiones 5a-c, 2-[5-(1-adamantyl)-2
      thioxo-1,3,4-thiadiazolin-3-yl]acetic acid 7, (+/-)-2-[5-(1-adamantyl)-2-thioxo
      1,3,4-thiadiazolin-3-yl]propionic acid 9, 3-[5-(1-adamantyl)-2-thioxo-1,3,4
      thiadiazolin-3-yl]propionic acid 11, N-[5-(1-adamantyl)-1,3,4-thiadiazol-2-yl]-N'
      arylthioureas 15a-c and 5-(1-adamantyl)-1,3,4-thiadiazoline-2-one 16, were
      synthesized and tested for in vitro activities against a panel of gram-positive
      and gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans.
      Compounds 7, 9, 15b and 15c displayed marked activity against the tested gram
      positive bacteria, while compound 3 was highly active against the tested gram
      negative bacteria. Compounds 4b, 7 and 15c were weakly or moderately active
      against C. albicans. In addition, the in vivo anti-inflammatory activity of the
      synthesized compounds was determined using the carrageenan-induced paw oedema
      method in rats. The propionic acid derivative 9 produced good dose-dependent anti
      inflammatory activity.

PMID- 20801554
TI  - Synthesis of the steroidal glycoside (25R)-3beta,16beta-diacetoxy-12,22-dioxo
      5alpha-cholestan-26-yl beta-D-glucopyranoside and its anti-cancer properties on
      cervicouterine HeLa, CaSki, and ViBo cells.
AB  - The synthesis of the new glycoside (25R)-3beta,16beta-diacetoxy-12,22-dioxo
      5alpha-cholestan-26-yl beta-D-glucopyranoside starting from hecogenin is
      described. This compound showed anti-cancer activity against cervicouterine
      cancer cells HeLa, CaSki and ViBo in the micromolar range. Its effect on cell
      proliferation, cell cycle and cell death is also described. The cytotoxic effect
      of the title compound on HeLa, CaSki and ViBo cells and human lymphocytes was
      evaluated through the LDH released in the culture supernatant, indicating that
      the main cell death process is not necrosis; the null effect on lymphocytes
      implies that it is not cytotoxic. The ability of this novel glycoside to induce
      apoptosis was investigated; several apoptosis events like chromatin condensation,
      formation of apoptotic bodies, as well as the increase in the expression of
      active caspase-3 and the fragmentation of DNA confirmed that the compound induced
      apoptosis in cervicouterine cancer cells. Significantly, the antiproliferative
      activity on tumor cells did not affect the proliferative potential of normal
      fibroblasts from cervix and peripheral blood lymphocytes. The glycoside showed
      selective antitumor activity and greater antiproliferative activity than its
      aglycon; it therefore serves as a promising lead candidate for further
      optimization.

PMID- 20801555
TI  - Synthesis and molluscicidal evaluation of some new pyrazole, isoxazole, pyridine,
      pyrimidine, 1,4-thiazine and 1,3,4-thiadiazine derivatives incorporating
      benzofuran moiety.
AB  - Chalcone derivative 3 was synthesized via the base catalyzed Claisen-Schmidt
      condensation and was used as a precursor for synthesizing pyrazoline 11,
      isoxazoline 12, pyrazoline carbothioamide 13, 5,6-dihydropyrimidine-2-(1H)-thione
      14 and aminopyridinecarbonitrile derivative 15. Bromination of 3 afforded the
      dibromo derivative 4. Monobromo derivative 5 obtained by boiling 4 in dry benzene
      in the presence of triethylamine. Fused thiadiazines 9a,b and 1,4-thiazine 9c
      derivatives were synthesized upon treatment of alpha-bromopropenone derivative 5
      with 4-amino-4H-1,2,4-triazole-3-thiol (6) or 1-amino-2-mercapto-5
      methylpyrimidin-4(1H)-one (7) or with 2-aminothiophenol (8) in ethanolic
      potassium hydroxide solution. The newly synthesized compounds were screened for
      their molluscicidal activities, whereas compounds 3, 4, 9a, 11 and 15 exhibited
      promising molluscicidal activities. On the other hand compounds 5, 9b, 9c, 12, 13
      and 14 showed a moderate effect as compared to the standard molluscicidal agent
      (Bayluscide).

PMID- 20801556
TI  - Effect of milrinone analogues on intracellular calcium increase in single living
      H9C2 cardiac cells.
AB  - The synthesis of milrinone analogues where the 4-pyridyl moiety was replaced by
      an ester or amide group is reported. Only amide derivatives are able to support
      intracellular calcium influx following chemical depolarization with 60 mM KCl in
      a percentage varying from 20 to 45% of differentiated H9C2 cardiomyocytes. Those
      cells were differentiated after chronic exposure to 10 nM retinoic acid which
      induces the expression of voltage-gated calcium channels. Analogues of milrinone
      containing an ester function did not show significant activity.

PMID- 20801557
TI  - The synthesis, structure and activity evaluation of pyrogallol and catechol
      derivatives as Helicobacter pylori urease inhibitors.
AB  - Some pyrogallol and catechol derivatives were synthesized, and their urease
      inhibitory activity was evaluated by using acetohydroxamic acid (AHA), a well
      known Helicobacter pylori urease inhibitor, as positive control. The assay
      results indicate that many compounds have showed potential inhibitory activity
      against H. pylori urease. 4-(4-Hydroxyphenethyl)phen-1,2-diol (2a) was found to
      be the most potent urease inhibitor with IC(50)s of 1.5+/-0.2 MUM for extracted
      fraction and 4.2+/-0.3 MUM for intact cell, at least 10 times and 20 times lower
      than those of AHA (IC(50) of 17.2+/-0.9 MUM, 100.6+/-13 MUM), respectively. This
      finding indicate that 2a would be a potential urease inhibitor deserves further
      research. Molecular dockings of 2a into H. pylori urease active site were
      performed for understanding the good activity observed.

PMID- 20801558
TI  - [Medical assessment after a pre-eclampsia: why? for whom? when? how? for what
      purpose?].
AB  - The internist has a relevant role in the medical assessment which is mandatory
      after every case of pre-eclampsia. This postnatal visit has to be performed to
      assert there is no underlying disorder such as chronic arterial hypertension or
      nephropathy, autoimmune disease or thrombophilia. This visit is also needed to
      provide information to the woman about what occurred during the pregnancy as well
      as to consider which would have to be done in case of a subsequent pregnancy.
      Long-term outcome had also to be taken into account considering risks for
      cardiac, arterial, renal and metabolic diseases. This visit is of outmost
      importance after very early-onset pre-eclampsia, and especially if it has already
      occurred. The postnatal visit after pre-eclampsia represents a very demonstrative
      example of the role that the internist can afford to the obstetrician in the
      management of medical disorders occurring during pregnancy and needing a specific
      expertise as well as a long-term follow-up.

PMID- 20801559
TI  - [Myelodysplastic syndrome with erythroblastopenia].
AB  - Myelodysplastic syndrome with erythroid hypoplasia or erythroblastopenia has not
      yet been clearly defined, and in most patients it is mistaken for acquired pure
      red cell aplasia. Including one additional patient reported in this article, a
      literature review revealed only 50 cases over the last 20 years. These patients
      were predominantly elderly males, all required regular packed red cell
      transfusions, and they had a poor prognosis, mainly because of acute
      transformation. The mechanisms of erythroid aplasia remain unclear. However,
      recent data suggest the association of an intrinsic stem cell defect with
      immunological implication.

PMID- 20801560
TI  - [Fever and back pain in a 73-year-old man].

PMID- 20801561
TI  - Longitudinal analysis of macronutrients and minerals in human milk produced by
      mothers of preterm infants.
AB  - BACKGROUND & AIMS: The primary objective of this study was to investigate the
      composition of breast milk of mothers with extremely preterm infants (<28 weeks)
      for their nutrient content over the first 8 weeks of lactation, and to compare
      premature to term milk. METHODS: Breast milk from 102 mothers who had delivered
      preterm infants and from 10 mothers who had delivered term infants were collected
      longitudinally. Fat, protein, carbohydrate, minerals and energy content were
      estimated weekly in each participant. Milk samples were representative of
      complete 24-h cycles. RESULTS: Carbohydrate, fat and energy concentrations were
      significantly higher in preterm than in term milk (p < 0.05). Protein content of
      both preterm and term milk decreased with the progress of lactation demonstrating
      significantly higher values in extremely preterm milk (<28 weeks) than in
      moderately preterm and term milk (p < 0.0001). The sodium levels of preterm milk
      were significantly elevated (p < 0.05) only in the first week. Other changes in
      mineral content were detected neither in preterm nor term milk. CONCLUSIONS: Our
      data provide new information on the macronutrient content of milk in mothers of
      extremely preterm infants with possible implications for the nutrition of this
      population.

PMID- 20801562
TI  - Impact of anthropogenic emissions and open biomass burning on regional
      carbonaceous aerosols in South China.
AB  - Carbonaceous aerosols were studied at three background sites in south and
      southwest China. Hok Tsui in Hong Kong had the highest concentrations of
      carbonaceous aerosols (OC=8.7+/-4.5MUg/m(3), EC=2.5+/-1.9MUg/m(3)) among the
      three sites, and Jianfeng Mountains in Hainan Island (OC=5.8+/-2.6MUg/m(3),
      EC=0.8+/-0.4MUg/m(3)) and Tengchong mountain over the east edge of the Tibetan
      Plateau (OC=4.8+/-4.0MUg/m(3), EC=0.5+/-0.4MUg/m(3)) showed similar concentration
      levels. Distinct seasonal patterns with higher concentrations during the winter,
      and lower concentrations during the summertime were observed, which may be caused
      by the changes of the regional emissions, and monsoon effects. The industrial and
      vehicular emissions in East, Southeast and South China, and the regional open
      biomass burning in the Indo-Myanmar region of Asia were probably the two major
      potential sources for carbonaceous matters in this region.

PMID- 20801563
TI  - Biodegradation of PAHs in soil: Influence of chemical structure, concentration
      and multiple amendment.
AB  - The influence of PAH chemical structure and concentration, added in either single
      (75 or 300 mg kg(-1)) or multiple (2 * 75, 2 * 150 or 4 * 75 mg kg(-1))
      applications as single- or multiple-contaminant systems, on the development of
      PAH biodegradation in a pristine soil was investigated. Development in microbial
      catabolic ability was assessed at 0, 28, 56 and 84 d by monitoring (14)C
      naphthalene, (14)C-phenanthrene and (14)C-pyrene mineralisation over 14 d in
      respirometric assays. The presence of other contaminants influenced the ability
      of the indigenous microflora to mineralise structurally different contaminants
      over time. (14)C-Naphthalene mineralisation was inhibited by the presence of
      other contaminants; whereas the presence of naphthalene significantly enhanced
      rates of mineralisation in multiple-contaminant systems containing (14)C
      phenanthrene and (14)C-pyrene. Generally, increasing the number of contaminant
      applications has implications for catabolic activity of soil microbes. It is
      suggested the toxic nature of PAHs retarded mineralisation at increased
      contaminant concentrations.

PMID- 20801564
TI  - Contamination of an arctic terrestrial food web with marine-derived persistent
      organic pollutants transported by breeding seabirds.
AB  - At Cape Vera, Devon Island (Nunavut, Canada), a colony of northern fulmars
      (Fulmarus glacialis) concentrates and releases contaminants through their guano
      to the environment. We determined whether persistent organic pollutants (POPs)
      from seabirds were transferred to coastal food webs. Snow buntings (Plectrophenax
      nivalis) were the most contaminated species, with ?PCB and ?DDT (mean: 168, 106
      ng/g ww) concentrations surpassing environmental guidelines for protecting
      wildlife. When examined collectively, PCB congeners and DDT in jewel lichen
      (Xanthoria elegans) were lower in samples taken farther from the seabird colony,
      and increased with increasing delta(15)N values. However, only concentrations of
      p'p-DDE:?DDT and PCB-95 were significantly correlated inversely with distance
      from the seabird cliffs. Linkages between marine-derived POPs and their
      concentrations in terrestrial mammals were less clear. Our study provides novel
      contaminant data for these species and supports biovector transport as a source
      of organic contaminants to certain components of the terrestrial food web.

PMID- 20801565
TI  - A simple tool to predict outcomes after kidney transplant.
AB  - BACKGROUND: Surprisingly few tools have been developed to predict outcomes after
      kidney transplant. STUDY DESIGN: Retrospective observational cohort study.
      SETTING & PARTICIPANTS: Adult patients from US Renal Data System (USRDS) data who
      underwent deceased donor kidney transplant in 2000-2006. PREDICTOR: Full and
      abbreviated prediction tools for graft loss using candidate predictor variables
      available in the USRDS registry, including data from the Organ Procurement and
      Transplantation Network and the Centers for Medicare & Medicaid Services End
      Stage Renal Disease Program. OUTCOMES: Graft loss within 5 years, defined as
      return to maintenance dialysis therapy, preemptive retransplant, or death with a
      functioning graft. MEASUREMENTS: We used Cox proportional hazards analyses to
      develop separate tools for assessment (1) pretransplant, (2) at 7 days
      posttransplant, and (3) at 1 year posttransplant to predict subsequent risk of
      graft loss within 5 years of transplant. We used measures of discrimination and
      explained variation to determine the number of variables needed to predict
      outcomes at each assessment time in the full and abbreviated equations, creating
      simple user-friendly prediction tools. RESULTS: Although we could identify 32,
      29, and 18 variables that predicted graft loss assessed pretransplant and at 7
      days and 1 year posttransplant ("full" models), 98% of the discriminatory ability
      and >80% of the variability explained by the full models could be achieved using
      only 11, 8, and 6 variables, respectively. LIMITATIONS: Comorbidity data were
      from the Centers for Medicare & Medicaid Medical Evidence Report, which may
      significantly underreport comorbid conditions; C statistic values may indicate
      only modest ability to discriminate risk for an individual patient. CONCLUSIONS:
      This method produced risk-prediction tools that can be used easily by patients
      and clinicians to aid in understanding the absolute and relative risk of graft
      loss within 5 years of transplant.

PMID- 20801566
TI  - Filtration markers in acute kidney injury.

PMID- 20801568
TI  - Association of low serum fetuin A levels with poor arteriovenous access patency
      in patients undergoing maintenance hemodialysis.
AB  - BACKGROUND: Fetuin A, a predictor of mortality in dialysis patients, is
      associated with vascular calcification and atherosclerosis in hemodialysis (HD)
      patients. Whether it predicts arteriovenous (AV) access patency is unknown. This
      study aimed to investigate the association between fetuin A and AV access patency
      in HD patients. STUDY DESIGN: Prospective observational study. SETTING &
      PARTICIPANTS: 238 prevalent HD patients (127 women and 111 men; mean age, 60 +/-
      12 years) were followed up for AV access patency for 32 months. PREDICTORS:
      Tertiles of baseline circulating fetuin A levels, corresponding to 0.15-0.25,
      0.26-0.32, and 0.33-0.51 g/L. OUTCOME: The major outcome was loss of unassisted
      AV access patency, defined as AV access thrombosis or need for intervention.
      MEASUREMENTS: Fetuin A and other markers of inflammation. RESULTS: 100 patients
      had loss of AV access patency (42%) on follow-up. Patients in the lowest fetuin A
      tertile had the worst AV access patency (log-rank test, chi(2) = 8.68; P = 0.01).
      Using Cox proportional hazards regression with patients in the lowest fetuin A
      tertile as reference, patients in the intermediate tertile had an HR of 0.49 (95%
      CI, 0.29-0.82), whereas those in the highest fetuin A tertile had an HR of 0.43
      (95% CI, 0.25-0.75) for loss of AV access patency. Similarly, considering
      patients using AV fistulas or grafts separately, patients in the highest fetuin A
      tertile had less risk of losing AV access patency than patients in the other
      tertiles (HR, 0.40 [95% CI, 0.19-0.84] for patients with AV fistulas and HR, 0.25
      [95% CI, 0.10-0.65] for patients with AV grafts). LIMITATIONS: Focus on the
      patency of prevalent rather than new AV access in maintenance hemodialysis
      patients. CONCLUSIONS: Fetuin A deficiency is associated with a higher risk of
      loss of AV access patency in either native AV fistulas or AV grafts in HD
      patients.

PMID- 20801569
TI  - Reducing the incidence of pseudohyperkalemia by avoiding making a fist during
      phlebotomy: a quality improvement report.
AB  - BACKGROUND: Pseudohyperkalemia is uncommon, but important. Local release of
      potassium caused by contraction of the forearm muscles from a tightly clenched
      fist or repeated fist clenching during phlebotomy is a recognized cause of
      pseudohyperkalemia. We investigated the use of a standard protocol to avoid fist
      clenching during phlebotomy. STUDY DESIGN: Quality improvement report. SETTING &
      PARTICIPANTS: In 7 healthy volunteers, 10 blood samples were collected over 10
      second intervals after 20 repeated fist clenching and unclenching movements. In
      86 healthy volunteers, 3 blood samples were collected with and without prior fist
      clenching. Between September 1, 2006, and June 30, 2007, peripheral venous blood
      samples were collected from 73,846 outpatients at Chiba University Hospital
      without a protocol to avoid fist clenching. Between July 1, 2007, and March 31,
      2009, blood samples were collected from 171,053 outpatients using the protocol.
      QUALITY IMPROVEMENT PLAN: After July 1, 2007, blood samples were collected from
      the basilic or cephalic vein without making a fist or by making a fist using
      minimal gripping strength. Also, when multiple specimens were obtained from 1
      patient, the specimen for measuring serum electrolytes was obtained after the
      other specimens. OUTCOMES & MEASUREMENTS: Pseudohyperkalemia, defined as
      unexplained serum potassium level >=6.5 mmol/L. RESULTS: In the 7 volunteers, the
      decrease in serum potassium levels after cessation of fist clenching ranged from
      8.4%-25.9%. In the 86 volunteers, the percentage with a decrease in serum
      potassium level >=0.2 mmol/L between the first and third samples was 25.6% versus
      6.7% with or without prior fist clenching, respectively. In clinical practice, we
      observed 8 cases of pseudohyperkalemia before implementing the protocol (0.0081%)
      and 1 case (0.00058%) after implementing the protocol (P = 0.001). LIMITATIONS:
      Causes of hyperkalemia before using precautions were assessed using retrospective
      analyses. CONCLUSIONS: Avoiding fist clenching during phlebotomy and not using
      the first specimen for electrolyte measurements when obtaining multiple specimens
      from a single patient can reduce the occurrence of pseudohyperkalemia.

PMID- 20801570
TI  - Estimation of GFR: a comparison of new and established equations.

PMID- 20801567
TI  - Relationship between body mass index and proteinuria in hypertensive
      nephrosclerosis: results from the African American Study of Kidney Disease and
      Hypertension (AASK) cohort.
AB  - BACKGROUND: Few studies have examined the association between obesity and markers
      of kidney injury in a chronic kidney disease population. We hypothesized that
      obesity is independently associated with proteinuria, a marker of chronic kidney
      disease progression. STUDY DESIGN: Observational cross-sectional analysis.
      SETTING & PARTICIPANTS: Post hoc analysis of baseline data for 652 participants
      in the African American Study of Kidney Disease (AASK). PREDICTORS: Obesity,
      determined using body mass index (BMI). MEASUREMENTS & OUTCOMES: Urine total
      protein-creatinine ratio and albumin-creatinine ratio measured in 24-hour urine
      collections. RESULTS: AASK participants had a mean age of 60.2 +/- 10.2 years and
      serum creatinine level of 2.3 +/- 1.5 mg/dL; 61.3% were men. Mean BMI was 31.4 +/
      7.0 kg/m(2). Approximately 70% of participants had a daily urine total protein
      excretion rate <300 mg/d. In linear regression analyses adjusted for sex, each 2
      kg/m(2) increase in BMI was associated with a 6.7% (95% CI, 3.2-10.4) and 9.4%
      (95% CI, 4.9-14.1) increase in urine total protein-creatinine and urine albumin
      creatinine ratios, respectively. In multivariable models adjusting for age, sex,
      systolic blood pressure, serum glucose level, uric acid level, and creatinine
      level, each 2-kg/m(2) increase in BMI was associated with a 3.5% (95% CI, 0.4
      6.7) and 5.6% (95% CI, 1.5-9.9) increase in proteinuria and albuminuria,
      respectively. The interaction between older age and BMI was statistically
      significant, indicating that this relationship was driven by younger AASK
      participants. LIMITATIONS: May not generalize to other populations; cross
      sectional analysis precludes statements regarding causality. CONCLUSIONS: BMI is
      associated independently with urine total protein and albumin excretion in
      African Americans with hypertensive nephrosclerosis, particularly in younger
      patients.

PMID- 20801571
TI  - Hemoglobin variability and mortality: confounding by disease severity.
AB  - BACKGROUND: Substantial variability in hemoglobin levels has been associated with
      increased mortality risk in hemodialysis patients. Variability also has been
      associated with concurrent comorbid conditions and hospitalization. Adequate
      adjustment for confounding by disease severity is needed to estimate the
      association of hemoglobin level variability with mortality risk. STUDY DESIGN:
      Retrospective cohort study. SETTING & PARTICIPANTS: Medicare hemodialysis
      patients in 3 groups: prevalent on July 1, 2006 (n = 133,246), prevalent on July
      1, 1996 (n = 78,602), and incident between January 1, 2005, and June 30, 2006 (n
      = 24,999). PREDICTOR: Hemoglobin level variability estimated using the residual
      deviation around the linear trend in hemoglobin levels during a 6-month entry
      period. OUTCOME: Time to death. MEASUREMENTS: We fit Cox models of 1-year
      mortality with and without adjustment for disease severity (comorbid conditions,
      hospitalization days, and months with hemoglobin level <10 g/dL), measured
      concurrently with hemoglobin level variability. RESULTS: Disease severity was
      associated positively with hemoglobin level variability in all groups. Before
      adjustment for disease severity, HRs for hemoglobin level variability were 1.27
      (95% CI, 1.24-1.31) per 1 g/dL for patients prevalent in 2006, 1.32 (95% CI, 1.27
      1.38) for patients prevalent in 1996, and 1.08 (95% CI, 1.03-1.13) for patients
      incident in 2005-2006. After adjustment, HRs for hemoglobin level variability
      were 1.02 (95% CI, 0.99-1.05), 1.07 (95% CI, 1.03-1.12), and 1.01 (95% CI, 0.95
      1.06), respectively. LIMITATIONS: We did not adjust for time-varying confounding
      of hemoglobin level; an inclusion requirement introduces potential selection
      bias; our findings may not apply to incident hemodialysis patients younger than
      65 years; assessment of comorbid conditions from claims is subject to
      misclassification, with possible residual confounding attributable to comorbid
      conditions; this observational study cannot prove causality. CONCLUSIONS: After
      adjustment for concurrent disease severity, evidence supporting an association
      between hemoglobin level variability and mortality risk was weak and
      inconsistent. The clinical utility of hemoglobin level variability may be
      limited.

PMID- 20801572
TI  - Prevalence and correlates of self-reported sexual dysfunction in CKD: a meta
      analysis of observational studies.
AB  - BACKGROUND: Sexual dysfunction is an under-recognized problem in men and women
      with chronic kidney disease (CKD). The prevalence, correlates, and predictors of
      this condition in patients with CKD have not been evaluated comprehensively.
      STUDY DESIGN: Systematic review and meta-analysis. SETTING & POPULATION: Patients
      treated using dialysis (dialysis patients), patients treated using transplant
      (transplant recipients), and patients with CKD not treated using dialysis or
      transplant (nondialysis nontransplant patients with CKD). SELECTION CRITERIA FOR
      STUDIES: Observational studies conducted in patients with CKD only or including a
      control group without CKD. PREDICTOR: Type of study population. OUTCOMES: Sexual
      dysfunction in men and women with CKD using validated tools, such as the
      International Index of Erectile Function, the Female Sexual Function Index
      (FSFI), or other measures as reported by study investigators. RESULTS: 50 studies
      (8,343 patients) of variable size (range, 16-1,023 patients) were included in
      this review. Almost all studies explored sexual dysfunction in men and
      specifically erectile dysfunction. The summary estimate of erectile dysfunction
      in men with CKD was 70% (95% CI, 62%-77%; 21 studies, 4,389 patients).
      Differences in reported prevalence rates of erectile dysfunction between
      different studies were attributable primarily to age, study populations, and type
      of study tool used to assess the presence of erectile dysfunction. In women, the
      reported prevalence of sexual dysfunction was assessed in only 306 patients from
      2 studies and ranged from 30%-80%. Compared with the general population, women
      with CKD had a significantly lower overall FSFI score (8 studies or subgroups,
      407 patients; mean difference, -9.28; 95% CI, -12.92 to -5.64). Increasing age,
      diabetes mellitus, and depression consistently were found to correlate with
      sexual dysfunction in 20 individual studies of patients with CKD using different
      methods. LIMITATIONS: Suboptimal and lack of uniform assessment of outcome
      measures. CONCLUSIONS: Sexual dysfunction is highly prevalent in both men and
      women with CKD, especially among those on dialysis. Larger studies enrolling
      different ethnic groups, using validated study tools, and analyzing the influence
      of various factors on the development of sexual dysfunction are needed.

PMID- 20801573
TI  - Voicing the lifeworld: Parental accounts of responsibility in genetic
      consultations for polycystic kidney disease.
AB  - When parents, who are carriers of or are affected by a genetic disorder, make
      decisions about the health risks faced by their children, there may be multiple
      factors to consider. These may include the medical benefits, the parents' own
      experiences of learning about their genetic status, and the future autonomy of
      the child. Health professionals face the challenge of explaining the possible
      burdens as well as benefits of testing children, while promoting open
      communication within families about the risk of an inherited condition. While
      genetic consultations do not in themselves constitute decision making, parents
      nevertheless account for their actions and decisions in an attempt to display
      parental responsibility. In this paper we explore the accounting practices of
      parents in genetic consultations, focusing on how they articulate their
      responsibility with regard to testing their at-risk children for autosomal
      dominant polycystic kidney disease (PKD) and the communication issues surrounding
      the testing process and the disclosing of test results. Based on eight audio
      recorded and transcribed genetic consultations from the UK, and drawing upon
      rhetorical discourse analysis, our findings suggest that (i) parents tend to
      foreground their practical 'lifeworld' considerations to justify their decisional
      actions; and (ii) there is considerable variation in the ways in which parents
      respond to information and advice offered by the professionals. The affected
      parent often presents their lifeworld concerns as outweighing, at least for the
      present moment, the longer term health benefits that might accrue to their
      children.

PMID- 20801574
TI  - Effect of increased private share of inpatient psychiatric resources on jail
      population growth: evidence from the United States.
AB  - There is a strong connection between the mental health and criminal justice
      systems. This research empirically tested whether the privatization of the
      inpatient mental health system alters this relationship, contributing to jail
      population growth. Using state-level panel data on U.S. states and the District
      of Columbia for the years 1985-1998, this study analyzed the relationship between
      the size of jail populations and private share of hospital psychiatric beds,
      first for overall private beds and then separately by private for-profit and
      nonprofit. Empirical models controlled for changes in mental health financing and
      resources, variations in criminal justice practice, and demographic and socio
      economic factors as well as state and year fixed effects. A method of
      instrumental variables was employed to make a stronger case for causal inference.
      Results show that a one-percentage point increase in the private for-profit share
      of psychiatric beds contributes to the growth of jail inmates by approximately
      2.3% annually. A greater private nonprofit share of psychiatric beds does not
      appear to influence the size of jail populations. These findings suggest that the
      increased private for-profit share of inpatient psychiatric resources undermines
      the safety-net and some control function of the mental health system and leads to
      a greater number of jail inmates.

PMID- 20801575
TI  - Horizontal and vertical attentional orienting in Parkinson's disease.
AB  - Patients with Parkinson's disease (PD) typically suffer from an asymmetric
      degeneration of dopaminergic cells in the substantia nigra, resulting in right
      sided (RPD) or left-sided (LPD) predominance of motor symptomatology. As the
      dopaminergic system is also involved in attention, we examined horizontal and
      vertical orienting of attention in LPD (N=10), RPD (N=9) and controls (N=10).
      Four LPD patients demonstrated left neglect and three LPD patients demonstrated
      neglect for the upper visual field. LPD patients demonstrated a slower
      performance in detecting targets in the left hemifield and did not demonstrate a
      validity effect, unlike RPD patients and controls. RPD patients performed similar
      to controls, with the exception of one patient showing left and another showing
      right neglect, and two RPD patients demonstrated lower neglect. In sum,
      horizontal and vertical orienting of attention can be affected in Parkinson's
      disease - particularly in LPD - from very subtle slowing to clinically detectable
      horizontal and/or vertical neglect.

PMID- 20801576
TI  - Focused echocardiographic evaluation in life support and peri-resuscitation of
      emergency patients: a prospective trial.
AB  - PURPOSE OF THE STUDY: Focused ultrasound is increasingly used in the emergency
      setting, with an ALS-compliant focused echocardiography algorithm proposed as an
      adjunct in peri-resuscitation care (FEEL). The purpose of this study was to
      evaluate the feasibility of FEEL in pre-hospital resuscitation, the incidence of
      potentially treatable conditions detected, and the influence on patient
      management. PATIENTS, MATERIALS AND METHODS: A prospective observational study in
      a pre-hospital emergency setting in patients actively undergoing cardio-pulmonary
      resuscitation or in a shock state. The FEEL protocol was applied by trained
      emergency doctors, following which a standardised report sheet was completed,
      including echo findings and any echo-directed change in management. These reports
      were then analysed independently. RESULTS: A total of 230 patients were included,
      with 204 undergoing a FEEL examination during ongoing cardiac arrest (100) and in
      a shock state (104). Images of diagnostic quality were obtained in 96%. In 35% of
      those with an ECG diagnosis of asystole, and 58% of those with PEA, coordinated
      cardiac motion was detected, and associated with increased survival.
      Echocardiographic findings altered management in 78% of cases. CONCLUSIONS:
      Application of ALS-compliant echocardiography in pre-hospital care is feasible,
      and alters diagnosis and management in a significant number of patients. Further
      research into its effect on patient outcomes is warranted.

PMID- 20801577
TI  - Evaluation of sustainability by a population living near fossil fuel resources in
      Northwestern Greece.
AB  - The emergence of sustainability as a goal in the management of fossil fuel
      resources is a result of the growing global environmental concern, and highlights
      some of the issues expected to be significant in coming years. In order to secure
      social acceptance, the mining industry has to face these challenges by engaging
      its many different stakeholders and examining their sustainability concerns. For
      this reason a questionnaire was conducted involving a simple random sampling of
      inhabitants near an area rich in fossil fuel resources, in order to gather
      respondents' views on social, economic and environmental benefits. The study
      discusses new subnational findings on public attitudes to regional
      sustainability, based on a quantitative research design. The site of the study
      was the energy-rich Greek region of Kozani, Western Macedonia, one of the
      country's energy hubs. The paper examines the future perspectives of the area.
      The conclusions can form a useful framework for energy policy in the wider Balkan
      area, which contains important fossil fuel resources.

PMID- 20801578
TI  - Restoration of foothills rough fescue grassland following pipeline disturbance in
      southwestern Alberta.
AB  - The effects of pipeline construction and reclamation techniques on the
      restoration of rough fescue plant communities following pipeline construction in
      southwestern Alberta, Canada were evaluated after 7-40 years. The pipeline
      construction right-of-way (ROW) sites varied from no recovery of rough fescue
      grassland to moderate recovery. The ROW sites had a higher proportion of
      introduced grasses and forbs, less topsoil, and poorer rangeland health than the
      adjacent undisturbed grassland. Within the ROW sites, less topsoil was present on
      those with larger diameter pipe and which had topsoil fully stripped from the ROW
      during construction. Introduced grasses, Festuca ovina (sheep fescue) and Poa
      compressa (Canada bluegrass), succeeded in establishment following seeding and
      persisted for at least 40 years. Poa pratensis (Kentucky bluegrass) dominated
      many of the ROW sites. Contributing factors to moderate recovery of rough fescue
      grassland were related to post-growing season pipeline construction, ideally,
      between August and March, summer or fall seeding, and minimum disturbance trench
      only stripping. Reclamation practices appeared more important than time since
      restoration in the restoration of rough fescue grassland.

PMID- 20801579
TI  - Influence of modified posterior reconstruction of the rhabdosphincter on early
      recovery of continence and anastomotic leakage rates after robot-assisted radical
      prostatectomy.
AB  - BACKGROUND: Posterior reconstruction (PR) of the rhabdosphincter has been
      previously described during retropubic radical prostatectomy, and shorter times
      to return of urinary continence were reported using this technical modification.
      This technique has also been applied during robot-assisted radical prostatectomy
      (RARP); however, contradictory results have been reported. OBJECTIVE: We describe
      here a modified technique for PR of the rhabdosphincter during RARP and report
      its impact on early recovery of urinary continence and on cystographic leakage
      rates. DESIGN, SETTING, AND PARTICIPANTS: We analyzed 803 consecutive patients
      who underwent RARP by a single surgeon over a 12-mo period: 330 without
      performing PR and 473 with PR. SURGICAL PROCEDURE: The reconstruction was
      performed using two 6-in 3-0 Poliglecaprone sutures tied together. The free edge
      of the remaining Denonvillier's fascia was identified after prostatectomy and
      approximated to the posterior aspect of the rhabdosphincter and the posterior
      median raphe using one arm of the continuous suture. The second layer of the
      reconstruction was then performed with the other arm of the suture, approximating
      the posterior lip of the bladder neck and vesicoprostatic muscle to the posterior
      urethral edge. MEASUREMENTS: Continence rates were assessed with a self
      administrated, validated questionnaire (Expanded Prostate Cancer Index Composite)
      at 1, 4, 12, and 24 wk after catheter removal. Continence was defined as the use
      of "no absorbent pads." Cystogram was performed in all patients on postoperative
      day 4 or 5 before catheter removal. RESULTS AND LIMITATIONS: There was no
      significant difference between the groups with respect to patient age, body mass
      index, prostate-specific antigen levels, prostate weight, American Urological
      Association symptom score, estimated blood loss, operative time, number of nerve
      sparing procedures, and days with catheter. In the PR group, the continence rates
      at 1, 4, 12, and 24 wk postoperatively were 22.7%, 42.7%, 91.8%, and 96.3%,
      respectively; in the non-PR group, the continence rates were 28.7%, 51.6%, 91.1%,
      and 97%, respectively. The modified PR technique resulted in significantly higher
      continence rates at 1 and 4 wk after catheter removal (p=0.048 and 0.016,
      respectively), although the continence rates at 12 and 24 wk were not
      significantly affected (p=0.908 and p=0.741, respectively). The median interval
      to recovery of continence was also statistically significantly shorter in the PR
      group (median: 4 wk; 95% confidence interval [CI]: 3.39-4.61) when compared to
      the non-PR group (median: 6 wk; 95% CI: 5.18-6.82; log-rank test, p=0.037).
      Finally, the incidence of cystographic leaks was lower in the PR group (0.4% vs
      2.1%; p=0.036). Although the patients' baseline characteristics were similar
      between the groups, the patients were not preoperatively randomized and unknown
      confounding factors may have influenced the results. CONCLUSIONS: Our modified PR
      combines the benefits of early recovery of continence reported with the original
      PR technique with a reinforced watertight closure of the posterior anastomotic
      wall. Shorter interval to recovery of continence and lower incidence of
      cystographic leaks were demonstrated with our PR technique when compared to RARP
      with no reconstruction.

PMID- 20801581
TI  - Oral administration of mannitol may be an effective treatment for ischemia
      reperfusion injury.
AB  - Inhalation of hydrogen gas has been proved to be an effective treatment for
      ischemia-reperfusion injury. There has been considerable evidence of hydrogen's
      protective effect to diseases related to oxidative injury, such as the ischemia
      reperfusion injury of the brain, liver and heart. Our previous studies
      demonstrated that intraperitoneal injection of hydrogen-rich saline protected
      hypoxic-ischemic brain injury, myocardial and intestine ischemia-reperfusion
      injury in rats. Bacteria in the large intestinal can produce endogenous hydrogen,
      and our preliminary experiments revealed that oral administration of mannitol in
      humans and animals can significantly increase the level of endogenous hydrogen.
      Therefore, we speculated that oral administration of mannitol may be effective
      against ischemia-reperfusion injury, which is a convenient, effective and unique
      treatment for ischemia-reperfusion injury.

PMID- 20801580
TI  - Clinical characteristics of veterans prescribed high doses of opioid medications
      for chronic non-cancer pain.
AB  - Little is known about patients prescribed high doses of opioids to treat chronic
      non-cancer pain, though these patients may be at higher risk for medication
      related complications. We describe the prevalence of high-dose opioid use and
      associated demographic and clinical characteristics among veterans treated in a
      VA regional healthcare network. Veterans with chronic non-cancer pain prescribed
      high doses of opioids (>= 180 mg/day morphine equivalent; n=478) for 90+
      consecutive days were compared to two groups with chronic pain: Traditional-dose
      (5-179 mg/day; n=500) or no opioid (n=500). High-dose opioid use occurred in 2.4%
      of all chronic pain patients and in 8.2% of all chronic pain patients prescribed
      opioids long-term. The average dose in the high-dose group was 324.9
      (SD=285.1)mg/day. The only significant demographic difference among groups was
      race (p=0.03) with black veterans less likely to receive high doses. High-dose
      patients were more likely to have four or more pain diagnoses and the highest
      rates of medical, psychiatric, and substance use disorders. After controlling for
      demographic factors and VA facility, neuropathy, low back pain, and nicotine
      dependence diagnoses were associated with increased likelihood of high-dose
      prescriptions. High-dose patients frequently did not receive care consistent with
      treatment guidelines: there was frequent use of short-acting opioids, urine drug
      screens were administered to only 25.7% of patients in the prior year, and 32.0%
      received concurrent benzodiazepine prescriptions, which may increase risk for
      overdose and death. Further study is needed to identify better predictors of high
      dose usage, as well as the efficacy and safety of such dosing.

PMID- 20801582
TI  - Maltose, a promising osmotic agent in peritoneal dialysis solution.
AB  - Peritoneal dialysis has undergone considerable development from a technological
      point of view, and osmotic agent has played the essential role in peritoneal
      dialysis fluid. Because the most commonly used osmotic agent is glucose and
      icodextrin, there are some disadvantages related to the use of glucose-based
      solutions and icodextrin. So it is urgent to develop a new peritoneal dialysis
      osmotic agent. According to these characteristics of glucose and icodextrin, it
      is promising to explore a better osmotic agent of peritoneal dialysis solution
      which is able to allow maintenance of the maximum ultrafiltration gradient, and
      prevent toxicity or accumulation of unwanted substances in the blood, being non
      toxic or less-toxic, furthermore the metabolite should not cause significant
      metabolic disturbance. Maltose may be one of promising osmotic agent and may put
      an important influence on development of peritoneal dialysis.

PMID- 20801583
TI  - Could the inter-individual variability in cocaine-induced psychotic effects
      influence the development of cocaine addiction? Towards a new pharmacogenetic
      approach to addictions.
AB  - Cocaine addiction is a chronic disease marked by relapses, co-morbidities and the
      importance of psychosocial consequences. The etiology of cocaine addiction is
      complex and involves three types of factors: environmental factors, factors
      linked to the specific effects of cocaine and genetic factors. The latter could
      explain 40-60% of the risk for developing an addiction. Several studies have
      looked for a link between cocaine addiction and the genes of the dopaminergic
      system: the genes DRD2, COMT, SLC6A3 (coding for the dopamine transporter DAT)
      and DBH (coding for the dopamine beta hydroxylase) but unfortunately very few
      well established results. Pharmacogenetic approach could be an interesting
      opportunity for the future. The gene DBH has particularly been linked with the
      psychotic effects caused by cocaine. This so-called cocaine-induced psychosis
      (CIP) or cocaine-induced paranoia may influence the development of cocaine
      addiction. Indeed, these psychotic symptoms during cocaine exposure could cause
      an aversive effect limiting the development of an addiction. Several functional
      alterations caused by different mutations of the genes involved in dopaminergic
      transmission (principally-1021C>T of the gene DBH, but also Val158Met of the gene
      COMT, TaqI A of the gene DRD2 and VNTR 9 repeat of the DAT) could result in a
      cocaine-induced psychosis prone phenotype. We are hypothesising that the
      appearance of CIP during the first contact with cocaine is associated with a
      lower risk of developing cocaine addiction. This protective effect could be
      associated with the presence of one or more polymorphisms associated with CIP. A
      pharmacogenetic approach studying combination of polymorphism could isolate a sub
      group of patients at risk for CIPs but more favorably protected from developing
      an addiction. This theory could enable a better understanding of the protective
      factors against cocaine addiction and offer new therapeutic or preventive targets
      in vulnerable sub-groups exposed to cocaine.

PMID- 20801584
TI  - Technique for targeting arteriovenous malformations using frameless image-guided
      robotic radiosurgery.
AB  - PURPOSE: To integrate three-dimensional (3D) digital rotation angiography (DRA)
      and two-dimensional (2D) digital subtraction angiography (DSA) imaging into a
      targeting methodology enabling comprehensive image-guided robotic radiosurgery of
      arteriovenous malformations (AVMs). METHODS AND MATERIALS: DRA geometric
      integrity was evaluated by imaging a phantom with embedded markers. Dedicated DSA
      acquisition modes with preset C-arm positions were configured. The geometric
      reproducibility of the presets was determined, and its impact on localization
      accuracy was evaluated. An imaging protocol composed of anterior-posterior and
      lateral DSA series in combination with a DRA run without couch displacement
      between acquisitions was introduced. Software was developed for registration of
      DSA and DRA (2D-3D) images to correct for: (a) small misalignments of the C-arm
      with respect to the estimated geometry of the set positions and (b) potential
      patient motion between image series. Within the software, correlated navigation
      of registered DRA and DSA images was incorporated to localize AVMs within a 3D
      image coordinate space. Subsequent treatment planning and delivery followed a
      standard image-guided robotic radiosurgery process. RESULTS: DRA spatial
      distortions were typically smaller than 0.3 mm throughout a 145-mm * 145-mm * 145
      mm volume. With 2D-3D image registration, localization uncertainties resulting
      from the achievable reproducibility of the C-arm set positions could be reduced
      to about 0.2 mm. Overall system-related localization uncertainty within the DRA
      coordinate space was 0.4 mm. Image-guided frameless robotic radiosurgical
      treatments with this technique were initiated. CONCLUSIONS: The integration of
      DRA and DSA into the process of nidus localization increases the confidence with
      which radiosurgical ablation of AVMs can be performed when using only an image
      guided technique. Such an approach can increase patient comfort, decrease time
      pressure on clinical and technical staff, and possibly reduce the number of
      cerebral angiograms needed for a particular patient.

PMID- 20801585
TI  - Exposure to alcohol, drugs and tobacco and the risk of subsequent suicidality:
      findings from the Mexican Adolescent Mental Health Survey.
AB  - AIMS: To examine whether the association between prevalence measures of
      suicidality and substance abuse/dependence among adolescents (1) is attenuated
      when temporal priority of exposure and outcome are taken into account, (2)
      extends to substance use (i.e. without disorder), (3) applies to tobacco use and
      dependence independent of illicit drugs and alcohol use/disorder, and (4) is
      confounded by comorbid mental illness. DESIGN: Discrete-time survival models were
      applied to retrospectively reported age of onset of first suicidal ideation, plan
      and attempt and age of onset of first substance use and disorder. PARTICIPANTS:
      3005 adolescents aged 12-17 residing in the Mexico City Metropolitan Area in
      2005. MEASUREMENTS: The World Mental Health computer-assisted adolescent version
      of the Composite International Diagnostic Interview was used to assess suicidal
      outcomes and psychiatric disorders including substance dependence/abuse.
      FINDINGS: Use of and dependence on tobacco is as strong a predictor of subsequent
      suicidality as is use of and dependence with abuse of alcohol and drugs. The
      association between substance use and subsequent suicidality is not fully
      accounted for by comorbid mental illness. CONCLUSION: Efforts to reduce the use
      as well as the abuse of alcohol, drugs and tobacco may help reduce the risk of
      subsequent suicidal behaviors among adolescents in Mexico.

PMID- 20801586
TI  - Psychiatric comorbidity in illicit drug users: substance-induced versus
      independent disorders.
AB  - BACKGROUND: Few studies have differentiated between independent and substance
      induced psychiatric disorders. In this study we determine the risks associated
      with independent and substance-induced psychiatric disorders among a sample of
      629 illicit drug users recruited from treatment and out of treatment settings.
      METHODS: Secondary analysis of five cross-sectional studies conducted during 2000
      2006. Independent and substance-induced DSM-IV psychiatric diagnoses were
      assessed using the Psychiatric Research Interview for Substance and Mental
      Disorders. RESULTS: Lifetime prevalence of Axis I disorders other than substance
      use disorder (SUD) was 41.8%, with independent major depression being the most
      prevalent (17%). Lifetime prevalence of antisocial or borderline personality
      disorders was 22.9%. In multinominal logistic regression analysis (SUD only as
      the reference group), being female (OR 2.45; 95% CI 1.59, 3.77) and having
      lifetime borderline personality disorder (OR 2.45; 95% CI 1.31, 4.59) remained
      significant variables in the group with independent disorders. In the group with
      substance-induced disorders, being recruited from an out of treatment setting (OR
      3.50; 95% CI 1.54, 7.97), being female (OR 2.38; 95% CI 1.24, 4.59) and the
      number of SUD (OR 1.31; 95% CI 1.10, 1.57) remained significant in the model.
      These variables were also significant in the group with both substance-induced
      and independent disorders, together with borderline personality disorder (OR
      2.53; 95% CI 1.03, 6.27). CONCLUSIONS: Illicit drug users show high prevalence of
      co-occurrence of mainly independent mood and anxiety psychiatric disorders. Being
      female, recruited from an out of treatment setting and the number of SUD, are
      risk factors for substance-induced disorders.

PMID- 20801587
TI  - Molecular characterization and expression profile of uterine serpin (SERPINA14)
      during different reproductive phases in water buffalo (Bubalus bubalis).
AB  - Uterine serpins (SERPINA14) play important roles during pregnancy in the farm
      animals. In this study, we have cloned and characterized cDNA sequence encoding
      the bubaline SERPINA14. We also studied its spatio-temporal expression in the
      uterine endometrium. The bubaline SERPINA14 has an open reading frame of 1299bp.
      Itshares ~90% identity with the SERPINA14 of other ruminant livestock species.
      Phylogenetically, bubaline SERPINA14 has been placed in the same clade that
      contained other mammalian homologues with a maximum identity to bovine SERPINA14.
      Using an anti-ovine monoclonal antibody, Western blot analysis of the uterine
      fluid of buffalo during the early stage of pregnancy confirmed the presence of
      SERPINA14 of about 48,000Da. The results of quantitative real time PCR (RT-qPCR)
      as well as in situ hybridization demonstrated a stage and tissue specific
      expression of bubaline SERPINA14. The level of SERPINA14 mRNA was low during
      stage I (Days 3-5), which increased (P<0.05) during stage II (Days 6-15) and then
      subsequently declined during stage III (Days 16-21) of the estrus cycle. During
      early pregnancy (Days ~30 of gestation) the level of SERPINA14 mRNA was as high
      as that during stage II of the estrus cycle. The SERPINA14 mRNA was localized in
      the glandular epithelium. The differential spatio-temporal expression of
      SERPINA14 in the uterine endometrium of buffalo suggests its plausible important
      roles in reproduction.

PMID- 20801588
TI  - Development of a homogeneous immunoassay for the detection of fentanyl in urine.
AB  - OBJECTIVE: Fentanyl is an extremely potent synthetic opioid that is widely used
      for chronic pain treatment; it is highly addictive and prone to abuse. The
      objective is to develop a high throughput homogeneous enzyme immunoassay (HEIA)
      for the rapid detection of fentanyl in human urine. METHODS: The HEIA is based on
      an immunoassay format in which both the antibody and enzyme-drug conjugate are in
      ready-to-use solution. In the absence of the target analyte in the specimen,
      enzyme-labeled drug conjugate binds to the antibody and results in a decrease of
      the enzyme (G6PDH) activity; hence there is lower absorbance at 340 nm. If the
      target analyte is present in the specimen, it competes with the enzyme-labeled
      drug to bind to limited amount of specific antibody that result in more enzyme
      activity and yields an increased absorbance at 340 nm. A polyclonal "in-house"
      antibody was selected that is capable of measuring fentanyl at low concentrations
      thus the assay detection limit was determined to be 1 ng/mL. The assay was
      validated with clinical urine specimens that previously confirmed positively or
      negatively for fentanyl/norfentanyl by LC-MS/MS. RESULTS: The intra-day (n = 20)
      and inter-day (n = 100) precision of the assay was less than 1% CV. No
      interferences from structurally unrelated and commonly ingested drugs were
      observed at a concentration of 10,000 ng/mL. A total of 209 LC-MS/MS confirmed
      urine specimens (149 positive and 57 negative samples) were analyzed by HEIA. The
      sensitivity, specificity, and accuracy values were 99%, 95%, and 98%
      respectively. CONCLUSION: This paper describes the development of a highly
      sensitive homogenous enzyme immunoassay for detecting fentanyl in urine at a cut
      off concentration of 2 ng/mL.

PMID- 20801589
TI  - [Multidrug-resistant tuberculosis management in three French hospitals].
AB  - INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) management is based on
      specific WHO guidelines. OBJECTIVES: The authors report MDR-TB management, in
      three French hospitals. METHOD: The authors retrospectively included patients
      with positive sample for multidrug-resistant Mycobacterium tuberculosis
      (isoniazid+rifampicin) from January 1, 2000 to December 31, 2005. The management
      was compared to the French and international prevalent guidelines. RESULTS:
      Sixteen patients were initially managed for MDR-TB by eight different medical
      teams over 6 successive years: 12 (75%) presented with primary MDR-TB. Management
      advice from the national referee center (NRC) for tuberculosis was reported in
      seven out of 14 treated cases. The median length of the intensive treatment was 2
      months (IQR: 1-3). Eight patients (58%) had an overall treatment length of 18
      months. The median number of effective drugs prescribed was 4 (IQR: 4-5). Nine
      patients (64%) were also managed in a sanatorium. Only eight patients (57%)
      completed the prescribed treatment. Nine patients were clinically cured and still
      followed-up, six of whom were bacteriologically cured. CONCLUSION: TB-MDR
      management was not conform to WHO guidelines in our study. Management in a
      sanatorium, NRC involvement, ambulatory DOT were highly beneficial.

PMID- 20801590
TI  - Oral vitamin D replacement is effective in chronic liver disease.
AB  - BACKGROUND & AIMS: End-stage chronic liver disease is associated with vitamin D
      deficiency but the prevalence across a broad-spectrum of liver disease is
      unknown. This study prospectively examines prevalence of vitamin D deficiency and
      response to replacement in chronic liver disease. METHODS: One hundred and fifty
      eight outpatients with chronic liver disease were enrolled. Serum 25
      hydroxyvitamin D (25[OH]D) levels were classified as: severely deficient less
      than 25 nmol/l, deficient 25-54 nmol/l or replete greater than 54 nmol/l. Sixty
      five of 158 (41%) had cirrhosis. RESULTS: 25[OH]D was suboptimal in 101/158
      (64%), including severe deficiency in 24 patients (15%). Vitamin D deficiency
      occurred in liver disease of all aetiologies, including patients with only mild
      liver disease. 25[OH]D increased by 60.0% (19.11 +/- 13.20 nmol/l) in patients
      with deficiency after vitamin D replacement and decreased by 25.2% (-18.33 +/-
      12.02 nmol/l) in non-treated initially replete patients over a median of 4
      months. CONCLUSIONS: Vitamin D deficiency improves with oral vitamin D
      supplementation and levels fall without supplementation. Chronic liver disease
      patients are at very high risk of vitamin D deficiency regardless of etiology or
      severity.

PMID- 20801591
TI  - Endometriosis of the appendix presenting as acute appendicitis: report of a case.

PMID- 20801592
TI  - Diffusion weighted imaging of female pelvic cancers: concepts and clinical
      applications.
AB  - Early applications of diffusion weighted magnetic resonance imaging (DWI) were
      limited to neuroimaging, concentrating either on stroke or brain tumours. With
      recent advances in MRI hardware and software DWI is now increasingly being
      investigated for cancer assessment throughout the body. Clinical applications of
      DWI relating to female pelvic cancers have largely concentrated on detection,
      localisation and staging of disease. More recently investigators have started to
      evaluate the ability of DWI for determining tumour histology and even predicting
      the outcome of chemoradiation treatment. This article reviews the physical
      concepts of MR diffusion weighting, illustrates the biophysical basis of
      diffusion contrast and reports the clinical applications of DWI for cervical,
      endometrial, ovarian, rectal and bladder tumours.

PMID- 20801593
TI  - The increased range of cervical flexed motion detected by radiographs in Hirayama
      disease.
AB  - PURPOSE: Cervical flexion movement is supposed to play an important role in the
      pathogenesis of Hirayama disease. But there is no report on the range of cervical
      flexed motion in this disease. The purpose of current study was to compare the
      range of cervical flexed motion in patients with Hirayama disease with the one in
      healthy controls using conventional lateral flexion radiographs of the cervical
      spine, and to investigate the diagnostic value of radiographs for Hirayama
      disease. MATERIALS AND METHODS: This prospective study was approved by a local
      institutional review board and written informed consent was obtained. From August
      2007 to March 2009, conventional flexion cervical radiographs and flexion
      cervical MRI were performed on 31 Hirayama disease patients (all men, age range,
      16-24 years, mean age, 19.52+/-2.29 years) and 40 control subjects (all men, age
      range, 16-25 years, mean age, 23.10+/-2.20 years). The segmental and overall
      range of cervical flexed motion was quantitatively measured. Receiver operating
      characteristic curve was calculated and the diagnostic accuracy was qualified by
      using the area under the curve Az. RESULTS: Both the segmental and overall range
      of cervical flexed motion of patients determined by flexion cervical radiographs
      was greater than that of controls. The Az value was 0.90, indicating a moderate
      to good ability of conventional flexion radiographs in the diagnosis of Hirayama
      disease. CONCLUSION: Hirayama disease patients have an increased flexed motion
      range of cervical spine which would contribute to the pathophysiological change
      and determine its treatment. Conventional flexion radiographs might be suitable
      to be used as first line radiographic examination, followed by MRI in cases of
      suspected Hirayama disease.

PMID- 20801594
TI  - Validity of T2 mapping in characterization of the regeneration tissue by bone
      marrow derived cell transplantation in osteochondral lesions of the ankle.
AB  - OBJECTIVE: Bone marrow derived cell transplantation (BMDCT) has been recently
      suggested as a possible surgical technique to repair osteochondral lesions. To
      date, no qualitative MRI studies have evaluated its efficacy. The aim of our
      study is to investigate the validity of MRI T2-mapping sequence in characterizing
      the reparative tissue obtained and its ability to correlate with clinical
      results. METHODS AND MATERIALS: 20 patients with an osteochondral lesion of the
      talus underwent BMDCT and were evaluated at 2 years follow up using MRI T2
      mapping sequence. 20 healthy volunteers were recruited as controls. MRI images
      were acquired using a protocol suggested by the International Cartilage Repair
      Society, MOCART scoring system and T2 mapping. Results were then correlated with
      AOFAS clinical score. RESULTS: AOFAS score increased from 66.8+/-14.5 pre
      operatively to 91.2+/-8.3 (p<0.0005) at 2 years follow-up. T2-relaxation time
      value of 35-45 ms was derived from healthy ankles evaluation and assumed as
      normal hyaline cartilage value and used as a control. Regenerated tissue with a
      T2-relaxation time value comparable to hyaline cartilage was found in all the
      cases treated, covering a mean of 78% of the repaired lesion area. A high
      clinical score was related directly to isointense signal in DPFSE fat sat
      (p=0.05), and percentage of regenerated hyaline cartilage (p=0.05), inversely to
      the percentage of regenerated fibrocartilage. Lesion's depth negatively related
      to the integrity of the repaired tissue's surface (tau=-0.523, p=0.007), and to
      the percentage of regenerated hyaline cartilage (rho=-0.546, p=0.013).
      CONCLUSIONS: Because of its ability to detect cartilage's quality and to
      correlate to the clinical score, MRI T2-mapping sequence integrated with Mocart
      score represent a valid, non-invasive technique for qualitative cartilage
      assessment after regenerative surgical procedures.

PMID- 20801595
TI  - Breoghania corrubedonensis gen. nov. sp. nov., a novel alphaproteobacterium
      isolated from a Galician beach (NW Spain) after the Prestige fuel oil spill, and
      emended description of the family Cohaesibacteraceae and the species
      Cohaesibacter gelatinilyticus.
AB  - A Gram-negative bacterium designated UBF-P1(T) was isolated from an enrichment
      culture established in nutrient supplemented artificial sea water with pyrene as
      a carbon source, and inoculated with a marine fuel oil-degrading consortium
      obtained from a sand sample collected from the beach of Corrubedo (A Coruna,
      Galicia, Spain) after the Prestige accidental oil spill. Phylogenetic analysis
      based on the almost complete 16S rRNA gene sequence affiliated strain UBF-P1(T)
      with the family Cohaesibacteraceae, Cohaesibacter gelatinilyticus (DSM 18289(T))
      being the closest relative species with 92% sequence similarity. Cells were
      irregular rods, motile, strictly aerobic, catalase and oxidase positive.
      Ubiquinone 10 was the major respiratory lipoquinone. The major polar lipids
      comprised diphosphatidylglycerol (DPG), phosphatidylglycerol (PG),
      phosphatidylethanolamine (PE), phosphatidylmonomethylethanolamine (PME), and
      phosphatidylcholine (PC). The major fatty acids detected were C(18:1)omega7c,
      C(19:0) cycloomega8c, and C(16:0). The G+C content of strain UBF-P1(T) was 63.9
      mol%. The taxonomic comparison with the closest relative based on genotypic,
      phenotypic and chemotaxonomic characteristics supported that strain UBF-P1(T)
      could be classified as a novel genus and species, for which the name Breoghania
      corrubedonensis gen. nov., sp. nov. is proposed. The type strain of this new
      taxon is UBF-P1(T) (CECT 7622, LMG 25482, DSM 23382).

PMID- 20801596
TI  - Thermodynamic aspects of solubility process of some sulfonamides.
AB  - The thermodynamic aspects of solubility process of sulfonamides with the general
      structures C(6)H(5)-SO(2)NH-C(6)H(4)-R (R=4-NO(2); 4-Cl) and 4-NH(2)-C(6)H(4)
      SO(2)NH-C(6)H(4)-R (R=4-NO(2); 4-CN; 4-Cl; 4-OMe; 4-C(2)H(5)) in water, phosphate
      buffer with pH 7.4 and n-octanol (as phases modeling various drug delivery
      pathways) were studied using the isothermal saturated method.

PMID- 20801597
TI  - Qualitative and quantitative studies on human B7.1-Fc fusion protein and the
      application in pharmacokinetic study in rhesus monkeys.
AB  - A sensitive, accurate, and precise enzyme immunoassay (EIA) for the
      quantification of intact human B7.1-Fc in rhesus monkey serum was validated, and
      the characteristics of B7.1 and Fc moiety of fusion protein were identified by
      surface plasmon resonance (SPR) and flow-cytometric method, respectively. B7.1-Fc
      bound to CD28 and CTLA-4 with K(d) values of 45.1 and 9.58 nM, respectively,
      which were very closed to the previous reports and the function of Fc moiety of
      fusion protein was also confirmed by Fc receptor binding assay and IL-8 releasing
      assay. To monitor the intact protein, the EIA method employed a sandwich scheme
      in which a multiclonal anti-human IgG (Fc specific) antibody and a monoclonal
      anti-human B7.1 antibody were served as capture and detection antibody,
      respectively. This EIA has a range of reliable response of 0.5-32 ng/ml. The LLOQ
      was established at 0.5 ng/ml. The intra-assay precision and accuracy were 6.1
      8.8% and (3.0-9.0)%, respectively with the inter-assay precision and accuracy
      were 5.7-11.5% and (10.7-9.1)%, respectively. Stability was established under
      certain conditions and no significant differences were found. This validated EIA
      assay was then successfully employed in the assessment of pharmacokinetic
      behavior of B7.1-Fc in rhesus monkeys after intravenous infusion, and a non
      linear characteristics was established across the investigated dosage range (32
      320 MUg/kg).

PMID- 20801598
TI  - Effect of the statin therapy on biochemical laboratory tests--a chemometrics
      study.
AB  - Statins are the first-line choice for lowering total and LDL cholesterol levels
      and very important medicaments for reducing the risk of coronary artery disease.
      The aim of this study is therefore assessment of the results of biochemical tests
      characterizing the condition of 172 patients before and after administration of
      statins. For this purpose, several chemometric tools, namely principal component
      analysis, cluster analysis, discriminant analysis, logistic regression, KNN
      classification, ROC analysis, descriptive statistics and ANOVA were used. Mutual
      relations of 11 biochemical laboratory tests, the patient's age and gender were
      investigated in detail. Achieved results enable to evaluate the extent of the
      statin treatment in each individual case. They may also help in monitoring the
      dynamic progression of the disease.

PMID- 20801599
TI  - Development, validation and transfer of a near infrared method to determine in
      line the end point of a fluidised drying process for commercial production
      batches of an approved oral solid dose pharmaceutical product.
AB  - Pharmaceutical companies are progressively adopting and introducing the
      principles of Quality by Design with the main purpose of assurance and built-in
      quality throughout the whole manufacturing process. Within this framework, a
      Partial Least Square (PLS) model, based on Near Infrared (NIR) spectra and
      humidity determinations, was built in order to determine in-line the drying end
      point of a fluidized bed process. The in-process method was successfully
      validated following the principles described within The International Conference
      on Harmonization of Technical Requirements for Registration of Pharmaceuticals
      for Human Use - ICH Q2 (r1) - Validation of Analytical Procedures: Text and
      Methodology. However, in some aspects, the cited guidelines were not appropriate
      to in-process methods developed and validated exclusively with in-line samples
      and implemented in dynamic systems, such as drying processes. In this work, a
      customized interpretation of guidelines has been adopted which provided the
      framework of evidence to support a validated application. The application has
      been submitted to the United States Food and Drug Administration (FDA) and The
      European Medicines Agency (EMA) during applications for grant of licences.
      Representatives from these Regulatory Authorities have specifically reviewed this
      novel application during on-site inspections, and have subsequently approved both
      the product and this application. Currently, the NIR method is implemented as a
      primary in-line method to control the drying end point in real-time (to below a
      control limit of not greater than 1.2% w/w) for commercial production batches of
      an approved, solid, oral-dose medicine. The implementation of this in-process
      method allows real-time control with benefits including a reduction in operation
      time and labour; sample handling and waste generation; and a reduced risk to
      product quality in further unit operations due to improved consistency of
      intermediate output at this stage. To date, this has achieved approximately 10%
      savings in energy efficiency and operational time for this part of the
      manufacturing process.

PMID- 20801600
TI  - A rare cause of widened mediastinum.

PMID- 20801601
TI  - Determinants and outcomes of patient-centered care.
AB  - OBJECTIVE: This paper defines an interactional analysis instrument to
      characterize patient-centered care and identify associated variables. METHODS: In
      this study, 509 new adult patients were randomized to care by family physicians
      and general internists. An adaption of the Davis Observation Code was used to
      measure a patient-centered practice style. The main outcome measures were visit
      specific satisfaction and healthcare resource utilization. RESULTS: In initial
      primary care visits, patient-centered practice style was positively associated
      with higher patient self-reported physical health status (p=0.0328), higher
      educational level (p=0.0050), and non-smoking status (p=0.0108); it was also
      observed more often in the interactions of family physicians compared to
      internists (p=0.0003). Controlling for patient sociodemographic variables, self
      reported health status, pain, health risk behaviors (obesity, alcohol abuse, and
      smoking), and clinic assignment, patient satisfaction was not related to the
      provision of patient-centered care. Moreover, a higher average amount of patient
      centered care recorded in visits throughout the one-year study period was
      significantly related to lower annual medical charges (p=0.0003). CONCLUSIONS:
      Patient-centered care was observed more often with family physician caring for
      healthier, more educated patients, and was associated with lower charges.
      PRACTICE IMPLICATIONS: Reduced annual medical care charges are an important
      outcome of patient-centered medical visits.

PMID- 20801602
TI  - Nurse-led psychological interventions to improve diabetes control: assessing
      competencies.
AB  - OBJECTIVE: To assess whether medical nurses can deliver motivational enhancement
      therapy (MET) and cognitive behavioural therapy (CBT) to a competent level and
      whether treatment fidelity is maintained. METHODS: Training consisted of
      classroom teaching, written materials, a training caseload, and audio-visual
      feedback. We used the Motivational Interviewing Treatment Integrity (MITI), the
      Revised 12-item Cognitive Therapy Scale (CTS-R), and components of the
      Motivational Interviewing Skill Code (MISC) to assess competency and treatment
      fidelity. Two independent clinical psychologists who were blind to the allocation
      rated a random selection of 40 sessions. RESULTS: Six nurses were trained in both
      interventions. For the MET the mean (SD) scores for empathy and spirit on the
      MITI scale were 5.1 (0.7) and 4.6 (1.0) respectively and for CBT the total mean
      (SD) CTS-R score was 52.1 (7.5), which was acceptable competency in both
      treatments. The two interventions were distinguishable. CONCLUSION: Results
      suggest that nurses can be trained to deliver diabetes-specific MET and CBT
      competently and maintain treatment fidelity. PRACTICE IMPLICATIONS: Findings of
      this study provide preliminary evidence to suggest that nurse-led psychological
      interventions could be incorporated into the traditional diabetes setting.

PMID- 20801603
TI  - Incidence, prevention, and management in spinal cord protection during TEVAR.

PMID- 20801604
TI  - Proof-of-principle study of steam ablation as novel thermal therapy for saphenous
      varicose veins.
AB  - INTRODUCTION: During the last decade, thermal ablation techniques such as
      endovenous laser ablation have been challenging the position of traditional
      surgery for the treatment of saphenous varicose veins. The newest method of
      thermal ablation is pulsated steam, which works by heating the vein with steam at
      120 degrees C. This study assessed the effectiveness of steam ablation of
      varicose veins in sheep and in humans. METHODS: The safety of the procedure in
      sheep was assessed by cardiovascular monitoring during treatment. We used
      ultrasound imaging to examine occlusion of the veins. Changes in treated veins
      were examined microscopically. In a pilot study, 20 veins in 19 patients with
      insufficiency of the great or the small saphenous vein were treated with pulsated
      steam ablation. Anatomic success, patient satisfaction, and complications were
      investigated for 6 months after the procedure. RESULTS: All veins in the sheep
      were occluded. No cardiovascular changes occurred during treatment. Histologic
      examination of treated veins showed typical changes of the vein wall, such as
      disappearance of the endothelial layer, fibrotic thrombosis, and major
      alterations in collagen fibers in the media. Steam ablation was effective in the
      19 patients: 13 of 20 veins were completely closed, and 7 showed a very small
      segment of recanalization after 6 months of follow-up that did not seem to be
      clinically relevant. Nine patients had some ecchymoses at the puncture site, and
      one patient had a transient superficial phlebitis. A median maximal pain score of
      1 (range, 0-10) was reported. No serious side effects, such as deep vein
      thrombosis, nerve injury, skin burns, or infections, were reported. Patients were
      very satisfied with the treatment, with a median satisfaction score of 9.25
      (range, 0-10). CONCLUSIONS: In this proof-of-principle study, pulsated steam
      ablation was an effective treatment for saphenous varicose veins.

PMID- 20801605
TI  - The effects of ginsenoside Rb1 on endothelial damage and ghrelin expression
      induced by hyperhomocysteine.
AB  - OBJECTIVE: Studies have indicated that ginsenoside Rb1 and ghrelin could both
      prevent homocysteine (Hcy)-induced endothelial dysfunction through the
      endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) mechanism. This study
      investigated whether endogenous ghrelin mediates the endothelial protection of
      ginsenosidee Rb1 through in vitro and in vivo experiments. METHODS: Rats were
      randomized into a control group, a hyperhomocysteine (HHcy) model group with a
      high methionine diet, a ginsenosides (GS) group, and HHcy plus GS group. Plasma
      ghrelin was detected by enzyme-linked immunosorbent assay. Aortic rings for
      control and HHcy groups were treated with ghrelin or not. Endothelium-dependent
      vasodilatation function was evaluated by the aortic ring assay, and the
      structural changes were visualized by hematoxylin and eosin staining. Human
      umbilical vein endothelial cells (HUVECs) were cultured, and the experimental
      conditions were optimized according to NO production. After treatment, the NO,
      ghrelin, and von Willebrand factor (vWF) levels in the media were detected and
      analyzed with linear regression. Ghrelin and eNOS expression were observed by
      cell immunohistochemical staining. Ghrelin receptor antagonist was used to detect
      the mechanism of ginsenoside Rb1 on NO production, which was reflected by
      diacetylated 4,5-diaminofluorescein-2 diacetate fluorescence. RESULTS: In vivo
      experiments demonstrated that plasma ghrelin levels in the HHcy group were
      significantly elevated vs controls (P < .05) and were significantly increased in
      the HHcy plus GS group (P < .01). Compared with control, endothelium-dependent
      vasodilatation function was greatly reduced in the HHcy group (P < .01), which
      was significantly increased in HHcy plus ghrelin group compared with HHcy group
      (P < .01). The arterial walls of HHcy group exhibited characteristic pathologic
      changes, which were repaired in HHcy plus ghrelin group. In vivo, compared with
      Hcy (200 MUM) group, HUVECs pretreated with ginsenoside Rb1 (10 MUM) for 30
      minutes showed significant increases in NO and ghrelin levels and evident
      reduction in vWF levels. Linear regression analysis demonstrated that ghrelin
      levels were significantly positively correlated with NO levels and significantly
      negatively correlated with vWF levels. The addition of Rb1 to Hcy also greatly
      reversed Hcy-induced downregulation of ghrelin and eNOS expression. Ghrelin
      inhibition significantly abolished the upregulation of NO levels induced by Rb1.
      CONCLUSION: Ghrelin can prevent Hcy-induced vascular endothelial dysfunction and
      structural damage. The compensatory elevation of plasma ghrelin levels in an Hcy
      induced endothelial injury model may be a protective response. Ginsenoside Rb1
      can significantly stimulate the ghrelin endocrine to inhibit endothelial injury.
      Ginsenoside also upregulates the NO signaling pathway reduced by Hcy through the
      ghrelin molecular mechanism.

PMID- 20801606
TI  - First United States experience of the TX2 Pro-Form thoracic delivery system.
AB  - OBJECTIVES: Failure to conform to the arch ("bird-beaking") can lead to endoleak
      and graft collapse after thoracic endovascular aortic repair. We report the first
      United States experience with the new TX2 Pro-Form (Cook Inc, Bloomington, Ind),
      a novel delivery system that became commercially available in October 2009,
      designed to enhance circumferential apposition of the TX2 thoracic endograft to
      the arch. METHODS: This was a single-institution retrospective study. Endograft
      to-arch conformance was quantitatively analyzed using intraoperative angiograms
      of consecutive, reverse chronologic cohorts of TX2 Pro-Form, TX2 Z-Trak (prior
      delivery system; Cook), and Gore TAG (W.L. Gore and Assoc, Flagstaff, Ariz). Only
      native aortic arch deployments in zones 2 and 3 were included. RESULTS: During a
      6-week period, 20 Pro-Form cases were performed, of which 17 patients met
      inclusion criteria. These were compared with 17 Z-Trak and 17 TAG patients.
      Endografts were successfully delivered to their intended proximal landing zones
      in all 51 patients. A higher proportion of dissections were treated in the Z-Trak
      (65%) and TAG (76%) patients (P = .03), but similar rates of zone 2/3 deployments
      (P = .30). Despite the mean arch angle being greatest for the Pro-Form patients
      (90 degrees  vs 74 degrees  vs 71 degrees , P = .18), the mean separation between
      the leading endograft edge and the aortic wall along the inner curvature of the
      arch was significantly less (1.4 vs 4.1 vs 5.7 mm; P = .0002), with complete
      apposition achieved in 65% of Pro-Form patients (18% Z-Trak, 6% TAG, P < .0001).
      This resulted in the lowest reduction in aortic luminal diameter at the proximal
      landing zone (5.5% vs 13.4% vs 19.3%; P = .0006) compared with Z-Trak and TAG.
      Rates of type Ia endoleak were similar (P = .38). CONCLUSIONS: The Pro-Form
      delivery system significantly improves endograft conformation to the arch,
      resulting in minimum bird-beaking even in severely angulated anatomies.

PMID- 20801608
TI  - Prospective randomized trial comparing endovenous laser ablation and surgery for
      treatment of primary great saphenous varicose veins with a 2-year follow-up.
AB  - BACKGROUND: Endovenous laser therapy (EVLT) for ablation of the great saphenous
      vein (GSV) is thought to minimize postoperative morbidity compared with high
      ligation and stripping (HL/S). Only a few randomized trials have reported early
      results. This prospective randomized trial compared EVLT (980 nm) and HL/S
      results at 1 and 2 years after the intervention. METHOD: Patients with
      symptomatic varicose veins due to GSV insufficiency were randomized to HL/S (100
      limbs) or EVLT (104 limbs). Four EVLT procedures failed primarily and were
      excluded. Phlebectomy and ligature of incompetent perforators were performed
      whenever indicated in both groups. Patients were re-examined clinically and by
      duplex ultrasound imaging preoperatively and at 12 days and at 1 and 2 years
      after treatment. Closure rate, complication rate, time to return to normal
      activity, the Aberdeen Varicose Vein Symptom Severity Score (AVVSS), the Varicose
      Venous Clinical Severity Score (VVCSS), and the Medical Outcome Study Short Form
      36 scores were also recorded. RESULTS: There were no differences in patient
      demographics, CEAP class, Widmer class, or severity scores between the groups.
      Simultaneous interventions did not differ between the groups. Similar times for
      the return to normal activity and scores for postoperative pain were reported. No
      major complications after treatment were recorded. HL/S limbs had significantly
      more postoperative hematomas than EVLT limbs, and EVLT patients reported more
      bruising. Follow-up at 1 year was 100% for HL/S and 99% for EVLT. Two GSVs in the
      EVLT group reopened and three partially reopened. No open GSVs occurred in HL/S
      limbs. Ninety-eight percent of the limbs in both groups were free of symptoms.
      VCSS, AVVSS, and Short Form-36 scores did not reveal any group differences. At 2
      years, no differences compared with 1-year results were observed, except that two
      more GSVs in the EVLT group were partially reopened. CONCLUSIONS: Abolition of
      GSV reflux and improvement in quality of life was similar after HL/S and EVLT.
      After EVLT, however, two GSVs were found completely reopened and five were
      partially reopened, which was significantly higher than after HL/S. A prolonged
      follow-up is ongoing.

PMID- 20801607
TI  - Endothelial cells are susceptible to rapid siRNA transfection and gene silencing
      ex vivo.
AB  - BACKGROUND: Endothelial gene silencing via small interfering RNA (siRNA)
      transfection represents a promising strategy for the control of vascular disease.
      Here, we demonstrate endothelial gene silencing in human saphenous vein using
      three rapid siRNA transfection techniques amenable for use in the operating room.
      METHODS: Control siRNA, Cy5 siRNA, or siRNA targeting glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) or endothelial specific nitric oxide synthase (eNOS) were
      applied to surplus human saphenous vein for 10 minutes by (i) soaking, (ii)
      applying 300 mm Hg hyperbaric pressure, or (iii) 120 mm Hg luminal distending
      pressure. Transfected vein segments were maintained in organ culture. siRNA
      delivery and gene silencing were assessed by tissue layer using confocal
      microscopy and immunohistochemistry. RESULTS: Distending pressure transfection
      yielded the highest levels of endothelial siRNA delivery (22% pixels fluorescing)
      and gene silencing (60% GAPDH knockdown, 55% eNOS knockdown) as compared with
      hyperbaric (12% pixels fluorescing, 36% GAPDH knockdown, 30% eNOS knockdown) or
      non-pressurized transfections (10% pixels fluorescing, 30% GAPDH knockdown, 25%
      eNOS knockdown). Cumulative endothelial siRNA delivery (16% pixels fluorescing)
      and gene silencing (46% GAPDH knockdown) exceeded levels achieved in the
      media/adventitia (8% pixels fluorescing, 24% GAPDH knockdown) across all
      transfection methods. CONCLUSION: Endothelial gene silencing is possible within
      the time frame and conditions of surgical application without the use of
      transfection reagents. The high sensitivity of endothelial cells to siRNA
      transfection marks the endothelium as a promising target of gene therapy in
      vascular disease.

PMID- 20801609
TI  - Eight-year experience with carotid artery stenting for correction of symptomatic
      and asymptomatic post-endarterectomy defects.
AB  - BACKGROUND: Carotid endarterectomy (CEA) has been shown to be superior to medical
      therapy alone in the prevention of stroke only if it can be safely performed (ie,
      with a complication rate less than 3% in asymptomatic patients and less than 6%
      in symptomatic patients). Technical defects are the most common cause of
      neurological complications after CEA, and their correction has traditionally been
      performed through standard surgical techniques. METHODS: From 1999, we started to
      treat intimal flaps, dissection, or partial thrombosis after CEA with carotid
      artery stenting (CAS). A retrospective analysis of the operating room registry
      and of the registry of our Interventional Cardiology laboratory was conducted in
      order to identify all the patients that underwent stenting of the internal
      carotid artery after CEA between January 2001 and June 2009. RESULTS: During the
      time period considered, 5012 CEA were performed at our institution and a total of
      34 patients (34/5012; 0.6%) were found to have received carotid stenting after
      CEA, both for symptomatic and asymptomatic defects. Immediate technical success
      was obtained in all patients. One major cerebrovascular adverse event (1/34; 3%)
      in the immediate perioperative period was recorded. At a mean follow-up of 18.6
      months (range, 3-84 months; median, 12 months), we did not observe any
      neurological symptoms related to the treated carotid artery, nor hemodynamic in
      stent restenosis. Long-term follow-up (ie, equal or greater than 4 years) was
      available for five patients: all patients remained event-free during the entire
      period. CONCLUSIONS: Our study adds to the assumption that CAS in post-CEA
      symptomatic and asymptomatic patients is safe and technically feasible, and
      represents a valid and quick alternative to standard surgical revision. Even if
      in a small group of patients, long-term results seem promising.

PMID- 20801610
TI  - Outcomes before and after initiation of an acute aortic treatment center.
AB  - BACKGROUND: Acute aortic syndromes remain life-threatening. Time is of the
      essence, as mortality rises with increasing time after the acute episode. The aim
      of this report is to show changes in practice and outcomes after the
      establishment of an acute aortic treatment center (AATC) to expedite the care of
      acute aortic syndromes in a major metropolitan area with the belief that "door to
      intervention time under 90 minutes" reduces mortality and morbidity from acute
      aortic disease. METHODS: A database of patients admitted with acute aortic
      disease (Type A and B aortic dissections, acute thoraco-abdominal aortic
      aneurysms, acute and ruptured abdominal aortic aneurysms) for 1 year prior to
      initiation (2007) and 1 year after initiation of the pathway (AATC) in 2008 was
      developed. Comorbidities were scored according to Society of Vascular Surgery
      criteria. Anatomic and functional outcomes were determined and categorized by
      Society of Vascular Surgery reporting criteria. Multivariate analysis was
      performed for categorical outcomes and Cox proportional hazard analyses for time
      dependent outcomes. RESULTS: Six hundred twenty-one patients reported with aortic
      disease to the cardiovascular services; 306 patients were considered to have
      acute disease. When compared with the year before the AATC was instituted, there
      was a 30% increase in the total number of admissions and a 25% increase in acute
      pathology after setting up the AATC (P = .02). There was a two-fold increase in
      thoracic aortic dissections admitted to the service. Initiation of the treatment
      pathway resulted in a highly significant 64% reduction in time to definitive
      therapy (526 +/- 557 vs 187 +/- 258 minutes, mean +/- SD pre-AATC vs AATC; P =
      .0001). Comorbidity scores were equivalent between the two cohorts. Despite the
      increase in acuity, mortality (4% vs 6%) and morbidity (41% vs 45%) rates were
      unchanged, and there was a significant decrease in intensive care unit length of
      stay (5 vs 4 days, pre-AATC cohort vs the AATC cohort), but total hospital length
      of stay (11 vs 10 days) was unchanged. There was no correlation between deaths
      within 30 days and length of stay in the intensive care unit. CONCLUSION:
      Establishment of a multidisciplinary AATC pathway was associated with a 30%
      increase in volume, 64% reduction in time to definitive treatment, improved
      throughput with reduced intensive care unit time, and maintained clinical
      efficacy despite an increase in acute admissions. These results suggest the
      concept be further evaluated.

PMID- 20801611
TI  - Clinical applications of robotic technology in vascular and endovascular surgery.
AB  - BACKGROUND: Emerging robotic technologies are increasingly being used by surgical
      disciplines to facilitate and improve performance of minimally invasive surgery.
      Robot-assisted intervention has recently been introduced into the field of
      vascular surgery to potentially enhance laparoscopic vascular and endovascular
      capabilities. The objective of this study was to review the current status of
      clinical robotic applications in vascular surgery. METHODS: A systematic
      literature search was performed in order to identify all published clinical
      studies related to robotic implementation in vascular intervention. Web-based
      search engines were searched using the keywords "surgical robotics," "robotic
      surgery," "robotics," "computer assisted surgery," and "vascular surgery" or
      "endovascular" for articles published between January 1990 and November 2009. An
      evaluation and critical overview of these studies is reported. In addition, an
      analysis and discussion of supporting evidence for robotic computer-enhanced
      telemanipulation systems in relation to their applications in laparoscopic
      vascular and endovascular surgery was undertaken. RESULTS: Seventeen articles
      reporting on clinical applications of robotics in laparoscopic vascular and
      endovascular surgery were detected. They were either case reports or
      retrospective patient series and prospective studies reporting laparoscopic
      vascular and endovascular treatments for patients using robotic technology.
      Minimal comparative clinical evidence to evaluate the advantages of robot
      assisted vascular procedures was identified. Robot-assisted laparoscopic aortic
      procedures have been reported by several studies with satisfactory results.
      Furthermore, the use of robotic technology as a sole modality for abdominal
      aortic aneurysm repair and expansion of its applications to splenic and renal
      artery aneurysm reconstruction have been described. Robotically steerable
      endovascular catheter systems have potential advantages over conventional
      catheterization systems. Promising results from applications in cardiac
      interventions and preclinical studies have urged their use in vascular surgery.
      Although successful applications in endovascular repair of abdominal aortic
      aneurysm and lower extremity arterial disease have been reported, published
      clinical experience with the endovascular robot is limited. CONCLUSIONS: Robotic
      technology may enhance vascular surgical techniques given preclinical evidence
      and early clinical reports. Further clinical studies are required to quantify its
      advantages over conventional treatments and define its role in vascular and
      endovascular surgery.

PMID- 20801612
TI  - One hundred vascular surgery citation "classics" from the surgical literature.

PMID- 20801613
TI  - Enhancing soft tissue ingrowth in proximal femoral arthroplasty with aortograft
      sleeve: a novel technique and early results.
AB  - Hip abductor function is critical to joint stability after proximal femoral
      arthroplasty. Normal soft tissue relationships are often violated during this
      procedure for complete tumor resection. Abductor insufficiency leads to abnormal
      gait mechanics and poor function. To improve soft tissue stability about a
      metallic proximal femoral endoprosthesis, we devised a novel use of vascular
      graft material. Two patients received a proximal femoral arthroplasty using this
      technique. These patients were followed for an average of 26.5 months. They
      demonstrated mean active hip abduction of 48 degrees , hip flexion of 90 degrees
      , mean Musculoskeletal Tumor Society score of 24 (80%), and Toronto Extremity
      Salvage Score of 80. We believe that this technique may be useful in achieving
      soft tissue stability about a metal endoprosthesis and may facilitate better
      function in patients undergoing this surgery.

PMID- 20801614
TI  - The lateral compartment in knees with isolated medial and patellofemoral
      osteoarthritis: a histologic analysis of articular cartilage.
AB  - The purpose of this study was to examine, at a histologic level, the articular
      cartilage of the radiographically normal lateral compartment in knees with
      isolated medial and possibly patellofemoral osteoarthritis. Twenty patients with
      radiographic evidence of medial compartment osteoarthritis and a radiographically
      osteoarthritis-free lateral compartment underwent a tricompartmental total knee
      arthroplasty. The resected lateral femoral condyle and lateral tibial plateau
      were evaluated by a fellowship-trained musculoskeletal pathologist for the
      presence, or lack thereof, of osteoarthritis at a microscopic level. Both the
      tibia and femur showed evidence of mild osteoarthritis at a microscopic level.
      This study shows that in patients with radiographic evidence of medial
      osteoarthritis and a radiographically normal lateral compartment, there is mild
      osteoarthritis in the lateral compartment.

PMID- 20801615
TI  - Five cases of failure of the tibial polyethylene insert locking mechanism in one
      design of constrained knee arthroplasty.
AB  - We describe 5 cases of failure of the locking mechanism of the polyethylene
      insert and tibial base-plate in one design of constrained condylar knee
      prosthesis due to disengagement of the locking screw. Loosening of the screw is
      believed to occur because of a counterclockwise torque created by the axial
      rotation of the femur on the tibia that occurs as the knee extends during gait.
      This torque is transmitted via the highly rotationally constrained femoral
      housing and tibial post to the locking screw. These failures suggest that an
      alternative locking mechanism should be considered for this prosthesis.

PMID- 20801616
TI  - An unusual complication of osteotome sinus floor elevation: benign paroxysmal
      positional vertigo.
AB  - Maxillary sinus floor elevation in cases of reduced vertical bone height in the
      posterior maxilla allows predictable implant placement. The osteotome sinus floor
      elevation (OSFE) technique has shorter healing and waiting times because the
      fixture can be placed in the implant recipient site simultaneously with the ridge
      augmentation. Implant site preparation is more comfortable for the patient when
      performed with spiral drills than with continuous malleting of the osteotomes.
      Membrane perforation is the most frequent complication with the OSFE technique;
      postoperative infection is rare. Benign paroxysmal positional vertigo (BPPV) may
      be a complication of OSFE and may cause stress if not identified correctly and
      managed properly. The available treatment options, diagnostic strategies and the
      pathophysiology of this unusual complication are discussed. The authors present a
      case in which intense BPPV developed during OSFE, focusing on dental and
      maxillofacial surgery as risk factors for this pathology.

PMID- 20801617
TI  - The association between antiepileptic drug and HMG-CoA reductase inhibitor co
      medication and cholesterol management in patients with epilepsy.
AB  - PURPOSE: Pharmacokinetic interactions have been demonstrated in enzyme-inducing
      antiepileptic drugs (EIAEDs) and statins; however, their clinical significance is
      not well established. The purpose of this study was to evaluate the association
      of EIAEDs and non-enzyme-inducing antiepileptic drugs (NEIAEDs) on statin dose
      adjustments and low-density lipoprotein (LDL) cholesterol levels in patients with
      epilepsy. METHODS: Retrospective insurance claims from 2000 to 2006 from the
      Ingenix Impact (formerly Integrated Health Care Information Services) database
      were analyzed. Two cohorts were compared, EIAEDs+statin and NEIAEDs+statin: 1118
      patients were analyzed (58% men; 66% aged >55 years); 506 (45%) initiated with an
      EIAED. Outcomes assessed included statin dose adjustments and, for a subset of
      subjects, risk of mean LDL >100mg/dL during the 12-month follow-up period.
      Descriptive statistics were calculated and regression models estimated. RESULTS:
      Among the EIAED group, 72% initiated with phenytoin; among the NEIAED group, 57%
      initiated with gabapentin. For the EIAED group, the risk of upward statin dose
      adjustments was significantly greater (odds ratio=1.36; P=0.04) compared with the
      NEIAED group; similarly, the risk of having mean LDL >100mg/dL was significantly
      greater (odds ratio=41.22; P=0.005) and increased during the follow-up period
      (+26.6mg/dL; P=0.001) for the EIAED group. DISCUSSION: This study suggests that
      concomitant use of EIAEDs and statins may be associated with reduced clinical
      effectiveness of statins. Patients with epilepsy who use EIAEDs and statins
      concomitantly may require greater vigilance for optimal cholesterol management.

PMID- 20801618
TI  - Induced Sezary syndrome PBMCs poorly express immune response genes up-regulated
      in stimulated memory T cells.
AB  - BACKGROUND: Dysfunctions in memory T cells contribute to various inflammatory
      autoimmune diseases and neoplasms. We hypothesize that investigating the
      differences of genetic profiles between resting and activated naive and memory T
      cells may provide insight into the characterization of abnormal memory T cells in
      diseases, such as Sezary syndrome (SS), a neoplasm composed of CD4(+) CD45RO(+)
      cells. OBJECTIVE: We determined genes distinctively expressed between resting and
      activated naive and memory cells. Levels of up-regulated genes in resting and
      activated memory cells were measured in SS PBMCs, which were largely comprised of
      CD4(+) CD45RO(+) cells, to quantitatively assess how different Sezary cells were
      from memory cells. METHODS: We compared gene expression profiles using high
      density oligo-microarrays between resting and activated naive and memory CD4(+) T
      cells. Differentially expressed genes were confirmed by qRT-PCR and
      immunoblotting. Levels of genes up-regulated in activated and resting memory T
      cells were determined in SS PBMCs by qRT-PCR. RESULTS: Activated memory cells
      expressed greater numbers of immune-mediated genes involved in effector function
      compared to naive cells in our microarray analysis and qRT-PCR. Nine out of 14
      genes with enhanced levels in activated memory cells had reduced levels in SS
      PBMCs (p<0.05). CONCLUSIONS: Activation of memory and naive CD4(+) T cells
      revealed a diverging gap in gene expression between these subsets, with memory
      cells expressing immune-related genes important for effector function. Many of
      these genes were markedly depressed in SS patients, implying Sezary cells are
      markedly impaired in mounting immune responses compared to memory cells.

PMID- 20801619
TI  - Thioglucose-stabilized gold nanoparticles as a novel platform for colorimetric
      bioassay based on nanoparticle aggregation.
AB  - Gold nanoparticles stabilized with thioglucose (TGlu-AuNPs), which have carboxyl
      groups on the particle surface as anchoring sites for covalent immobilization of
      biomolecules, were prepared by the chemical reduction of HAuCl4 using 1-thio-beta
      D-glucose as a reducing and stabilizing agent, and their application to
      colorimetric bioassay was demonstrated using the carbohydrate-lectin system. p
      Aminophenyl alpha-D-mannose (Man-NH2) was covalently attached by a conventional
      method to the activated carboxyl groups on the TGlu-AuNPs. On addition of Con A
      to the Man-AuNPs, multiple binding events occurred between Con A and the mannoses
      immobilized on the particle surface. This Con A-induced aggregation resulted in a
      significant red shift in local surface plasmon resonance. The binding isotherm
      showed a sigmoidal curve, indicating cooperativity in the binding of Con A and
      the Man-AuNPs. In addition, Hill plots showed two nonequivalent binding modes,
      with the Kd values for high- and low-affinity binding of 11.3 and 66.5 pM,
      respectively, which was significantly lower than that for methyl-alpha-D-mannose
      binding to Con A. The enhanced binding affinity between Man-AuNPs and Con A
      involves the cluster effect of the carbohydrate groups on the AuNPs. A linear
      correlation curve was obtained in the range 10-100 nM (R2=0.983). The limit of
      detection (LOD) for Con A was 9.0 nM in aqueous buffer, which is comparable to
      that of other conventional methods such as ELISA.

PMID- 20801620
TI  - Surface forces and protein adsorption on dextran- and polyethylene glycol
      modified polydimethylsiloxane.
AB  - Dextran and polyethylene glycol (PEG) are often covalently bound to the surface
      of polydimethylsiloxane (PDMS) for the purpose of modifying its hydrophilicity
      and biocompatibility. In this work, the effects of the dextran and PEG on the
      morphology, wetting, and surface charge of the resulting surfaces were quantified
      and correlated with changes in the amount of fibrinogen and albumin adsorbed from
      aqueous solution. PDMS films were functionalized in a microwave oxygen plasma to
      create surface hydroxyl groups that were subsequently aminated by incubation in a
      (3-aminopropyl)trimethoxysilane (APTES) solution. Oxidized dextran and PEG
      aldehyde were linked to the surface amines via reductive amination. This process
      resulted in low surface coverage of immobilized PEG in the end-on conformation
      and a more uniform and dense distribution of side-on immobilized dextran. The
      immobilized dextran reduced the contact angle of the PDMS film from 109 degrees 
      to 80 degrees  and neutralized the zeta potential over the pH range from 3 to 11.
      An atomic force microscope was used to measure the interaction force between the
      modified PDMS and a model hydrophobic surface (polystyrene latex) and a model
      hydrophilic surface (silica) in aqueous solution to show that van der Waals and
      hydrophobic attractive forces are the dominant forces for protein adsorption in
      this system. The PEG- and dextran-modified PDMS were exposed to BSA and
      fibrinogen to test their resistance to protein adsorption. The coatings were
      ineffective at reducing the adsorption of either molecule, and the dextran
      modification of the PDMS caused more BSA to adsorb than in the case of the
      unmodified PDMS.

PMID- 20801621
TI  - Preparation of near-infrared light absorbing gold nanoparticles using
      polyethylene glycol-attached dendrimers.
AB  - The photochemical properties of gold nanoparticles (Au NPs) are largely
      influenced by their size and morphology. Stably dispersed Au NPs that absorb near
      infrared (NIR) light are useful for biomedical applications. We prepared well
      dispersed NIR-absorbing Au NPs using seeding growth from Au NPs encapsulated in
      polyethylene glycol (PEG)-attached dendrimers. Formaldehyde was used as a
      reductant to prepare gold nanoparticles with convex-concave surfaces. Low pH and
      an appropriate amount of gold ion were required to prepare Au NPs that absorbed
      NIR-light. Interestingly, the encapsulation of Au NPs within the PEGylated
      dendrimers was important for preparation of NIR-absorbing Au NPs. Transmission
      electron microscope (TEM) analysis showed that these Au NPs had convex-concave
      surfaces and large diameters. This paper presents a novel preparation method for
      NIR-responsive Au NPs by reduction with formaldehyde.

PMID- 20801622
TI  - Calcium phosphate solubility-In the blind spot.

PMID- 20801623
TI  - Concentration effect of gold nanoparticles on proliferation of keratinocytes.
AB  - 34 nm gold nanoparticles with good stability were synthesized and characterized
      and their effect (as a function of concentration) on the proliferation of
      keratinocytes was evaluated by means of MTT and nucleolar organizer region
      (AgNOR) count (silver staining). The cell morphology was observed by scanning
      electron microscopy (SEM) and transmission electron microscopy (TEM). The results
      demonstrate that a low concentration of gold nanoparticles enhances the
      proliferation of keratinocytes. Specifically, a concentration of 5.0 ppm gold
      nanoparticle has the best effect on the promotion of cell growth. In the
      experiment group, the AgNOR-positive areas and AgNOR area/nuclear area ratios of
      keratinocytes co-cultured with 5.0 ppm gold nanoparticles were greater than those
      in the control group (p<0.01). At a level greater than 10.0 ppm, gold
      nanoparticles were found to have a cytotoxic effect on keratinocytes. It is
      concluded that a low concentration of gold nanoparticles may be used as a
      biomedical material in skin tissue engineering.

PMID- 20801624
TI  - Characterization and preparation of core-shell type nanoparticle for
      encapsulation of anticancer drug.
AB  - The aim of this study is to prepare delivery vehicles of paclitaxel using low
      molecular weight water-soluble chitosan (LMWSC) and evaluate them as an
      anticancer drug delivery system. LMWSC was modified with methoxy polyethylene
      glycol (LMWSC-MPEG, ChitoPEG), and then it was conjugated with cholesterol (LMWSC
      MPEG-Chol). Core-shell type LMWSC-MPEG-Chol nanoparticles (LMWSC-NPs) were
      prepared by the dialysis method, and the core-shell structure was confirmed by 1H
      NMR analysis. To this polymer, paclitaxel was encapsulated and core-shell type
      nanoparticles were prepared. The release tests indicated that release of
      paclitaxel from the core-shell type nanoparticles and its transport across the
      dialysis membrane was slower than dialysis of free paclitaxel. In a cytotoxicity
      study using CT26 cell, the paclitaxel-encapsulated core-shell type nanoparticles
      (LMWSC-NPs) showed a toxicity against tumor cells similar to paclitaxel itself.
      The results of a tumor inhibition test with CT26 implanted upon mouse tumor
      models in vivo indicated that the application of a dose of 10 mg/kg of LMWSC-NPT
      showed a superior survival rate, and a slower tumor growth than when paclitaxel
      alone was administered, although the tumor growth and survival rate were not
      significantly changed at a dose of 2 mg/kg. The LMWSC-NPT dose above 10mg/kg
      showed a superior antitumor activity.

PMID- 20801625
TI  - xCT modulation in gliomas: relevance to energy metabolism and tumor
      microenvironment normalization.
AB  - Several nutrient transporters impacting the glutathione/redox cycle regulation
      and cell proliferation have been identified in cancer, which render these
      transporters potential prime targets for cytotoxic anticancer therapy. One
      promising transporter is system X(c)(-), also known as xCT (SLC7a11), which is
      expressed in various cancers including primary malignant brain tumors (gliomas).
      An important biological feature of these transporters, and in particular of xCT
      is its specific modulation of the tumor microenvironment leading to growth
      advantage for cancer. Thus, tumor microenvironment shaping by xCT inhibition
      revealed a so far neglected hallmark of gliomas, i.e. tumor-induced neurotoxicity
      and its impact on the development of peritumoral brain swelling. This review here
      discusses available pharmacological tools for the tumor microenvironment
      normalization, in the context of perifocal edema and the Warburg effect and
      highlights the implications of such metabolic normalization approach in the
      design of new therapies.

PMID- 20801626
TI  - Comparative functional structure of the olfactory mucosa in the domestic dog and
      sheep.
AB  - Olfactory acuity differs among animal species depending on age and dependence on
      smell. However, the attendant functional anatomy has not been elucidated. We
      sought to determine the functional structure of the olfactory mucosa in suckling
      and adult dog and sheep. Mucosal samples harvested from ethmoturbinates were
      analyzed qualitatively and quantitatively. In both species, the olfactory mucosa
      comprised olfactory, supporting and basal cells, and a lamina propria containing
      bundles of olfactory cell axons, Bowman's glands and vascular elements. The
      olfactory cells terminated apically with an expanded knob, from which cilia
      projected in a radial fashion from its base and in form of a tuft from its apex
      in the dog and the sheep respectively. Olfactory cilia per knob were more
      numerous in the dog (19 +/- 3) compared to the sheep (7 +/- 2) (p<0.05). In the
      dog, axonal bundles exhibited one to two centrally located capillaries and the
      bundles were of greater diameters (73.3 +/- 10.3 MUm) than those of the sheep
      (50.6 +/- 6.8 MUm), which had no capillaries. From suckling to adulthood in the
      dog, the packing density of the olfactory and supporting cells increased by 22.5%
      and 12.6% respectively. Surprisingly in the sheep, the density of the olfactory
      cells decreased by 26.2% while that of the supportive cells showed no change.
      Overall epithelial thickness reached 72.5 +/- 2.9 MUm in the dog and 56.8 +/- 3.1
      MUm in the sheep. These observations suggest that the mucosa is better
      structurally refined during maturation in the dog than in the sheep.

PMID- 20801627
TI  - Air pollution and children's respiratory symptoms in six cities of Northern
      China.
AB  - OBJECTIVE: The associations between air pollution and children's respiratory
      health in the high pollution range have not yet been clearly characterized. We
      evaluated the effects of outdoor air pollution on respiratory morbidity in
      children selected from multiple sites in a heavy industrial province of
      northeastern China. METHODS: The study included 11,860 children aged 3-12 years,
      selected from 18 districts of 6 cities in Liaoning province, the participation
      rate is 89.9%. Informed consent and written responses to surveys about children's
      historic and current health status, personal and household characteristics, and
      other information were obtained from parents. A two-stage regression approach was
      applied in data analyses. RESULTS: There were wide gradients for TSP (188-689
      MUg/m(3)), SO(2) (14-140 MUg/m(3) and NO(2) (29-94 MUg/m(3)) across the 18
      districts of 6 cities. The three air pollutants significantly increased the
      prevalence of persistent cough (21-28%), persistent phlegm (21-30%) and current
      asthma (39-56%) for each interquartile range increment (172 MUg/m(3) for TSP, 69
      MUg/m(3) for SO(2), 30 MUg/m(3) for NO(2)), showing larger between-city effects
      than within-city. Rates of respiratory symptoms were significantly higher for
      children with younger age, atopy, respiratory disease in early age, family
      history of asthma or chronic bronchitis, and tobacco smoke exposure. CONCLUSION:
      The high levels of outdoor air pollution in north China are positively associated
      with children's respiratory symptoms, the associations with TSP appear to be
      stronger than SO(2) and NO(2).

PMID- 20801628
TI  - Elevated HDL cholesterol levels are associated with osteoporosis in lung
      transplant candidates with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Osteoporosis is common in advanced COPD and worsens rapidly after
      transplantation, potentially impairing quality of life. Increased high density
      lipoprotein cholesterol (HDLc) has been observed in COPD and linked with
      osteoporosis in the general population. This association has not been previously
      examined in COPD. METHODS: We reviewed the records of 245 COPD patients referred
      for lung transplant evaluation. Osteoporosis was defined by either dual energy X
      ray absorptiometry scan or use of osteoporosis medications. The presence or
      absence of osteoporosis could be ascertained in 152 subjects. Cholesterol values
      and other clinical variables were assessed for their association with
      osteoporosis. RESULTS: Clinical factors associated with osteoporosis included
      lower BMI [OR 0.81, 95% CI 0.73-0.90], higher HDLc [OR 1.04, 95% CI 1.02 to
      1.07], and worse lung function. HDLc was an independent predictor of OP and
      demonstrated an inverse linear correlation with T-scores (r = -0.21, p = 0.05),
      which was stronger amongst males (r = -0.45, p = 0.004). CONCLUSION: In COPD
      patients referred for lung transplantation, osteoporosis is highly prevalent.
      Raised HDLc levels are common in this group and are independently associated with
      OP.

PMID- 20801629
TI  - Role of tumor necrosis factor alpha (TNFalpha) in the onset of fructose-induced
      nonalcoholic fatty liver disease in mice.
AB  - Tumor necrosis factor alpha (TNFalpha) is known to be involved in dysregulation
      of hepatic lipid metabolism and insulin signaling. However, whether TNFalpha also
      plays a casual role in the onset of fructose-induced nonalcoholic fatty liver
      disease (NAFLD) has not yet been determined. Therefore, wild-type and TNFalpha
      receptor 1 (TNFR1)-/- mice were fed with either 30% fructose solution or plain
      tap water. Hepatic triglycerides, markers of inflammation and ATP concentration
      as well as plasma ALT levels were determined. Hepatic PAI-1, SREBP-1, FAS mRNA
      expression was assessed by real-time RT-PCR. Furthermore, lipid peroxidation and
      indices of insulin resistance were determined in liver tissue and plasma. In
      comparison to water controls, chronic intake of 30% fructose solution caused a
      significant ~5-fold increase in triglyceride accumulation and neutrophil
      infiltration in livers of wild-type mice and a ~8-fold increase in plasma ALT
      levels. In TNFR1-/- mice, hepatic steatosis was attenuated and neutrophil
      infiltration in the liver as well as plasma ALT levels was similar to water
      controls. The protective effect of the TNFR1 deletion against the onset of
      fructose-induced steatosis was associated with increased phospho AMPK and Akt
      levels, decreased SREBP-1 and FAS expression in the liver and decreased RBP4
      plasma levels, whereas hepatic lipid peroxidation, iNOS protein and ATP levels
      were similar between wild-type and TNFR1-/- mice fed fructose. Taken together,
      these data suggest that TNFalpha plays a casual role in the onset of fructose
      induced liver damage as well as insulin resistance in mice through signaling
      cascades downstream of TNFR1.

PMID- 20801630
TI  - Ascorbate promotes carbon tetrachloride-induced hepatic injury in senescence
      marker protein 30-deficient mice by enhancing inflammation.
AB  - The genetic deletion of the senescence marker protein 30 (SMP30) gene results in
      ascorbate deficiency and the premature aging processes in mice. Apparent liver
      injury of SMP30(-/-) mice was less severe than those of wild type (WT) mice, upon
      chronic CCl(4) injection. The purpose of this study was to investigate the
      pathophysiology underlying the mild CCl(4) toxicity in SMP30(-/-) mice. Along
      with the lower level of serum alanine aminotransferase, the livers of SMP30(-/-)
      mice revealed a lesser glycogen depletion, a decrease in c-Jun N-terminal kinase
      (JNK)-mediated inflammatory signaling in parallel with tumor necrosis factor
      alpha and interleukin-1 beta, inducible nitric oxide synthase and glutathione
      peroxidase, and the lower lipid peroxidation as compared to those of WT mice.
      CCl(4)-induced proliferation, measured by the expression of proliferating cell
      nuclear antigen, was low in SMP30(-/-) mice as compared with that of WT mice
      whereas the levels of p21 and Bax were comparable to those of the CCl(4)-treated
      WT mice. Moreover, CCl(4) toxicity in ascorbate-fed SMP30(-/-) mice was
      comparable to that of the CCl(4)-alone treated WT mice, accompanied by an
      increase in the above mentioned factors. Conversely, ascorbate partly compensated
      for the CCl(4)-induced oxidative stress in WT mice, indicating that sufficient
      ascorbate may be required for an antioxidant function under severe levels of
      oxidative stress. Our data suggest that the restoration of ascorbate-deficiency
      reverses a sluggish immune system into an activated condition by an increase in
      JNK-mediated inflammation and free radical cascade; thus leading to accelerated
      hepatic damage in SMP30(-/-) mice.

PMID- 20801631
TI  - An increase in liver PPARgamma2 is an initial event to induce fatty liver in
      response to a diet high in butter: PPARgamma2 knockdown improves fatty liver
      induced by high-saturated fat.
AB  - The effects of a diet rich in saturated fat on fatty liver formation and the
      related mechanisms that induce fatty liver were examined. C57BL/6J mice were fed
      butter or safflower oil as a high-fat (HF) diet (40% fat calories) for 2, 4, 10,
      or 17 weeks. Although both HF diets induced similar levels of obesity, HF butter
      fed mice showed a two to threefold increase in liver triacylglycerol (TG)
      concentration compared to HF safflower oil-fed mice at 4 or 10 weeks without
      hyperinsulinemia. At 4 weeks, increases in peroxisome proliferator-activated
      receptor gamma2 (PPARgamma2), CD36, and adipose differentiation-related protein
      (ADRP) mRNAs were observed in HF butter-fed mice; at 10 weeks, an increase in
      sterol regulatory element-binding protein-1c (SREBP-1c) was observed; at 17
      weeks, these increases were attenuated. At 4 weeks, a single injection of
      adenoviral vector-based short hairpin interfering RNA against PPARgamma2 in HF
      butter-fed mice reduced PPARgamma protein and mRNA of its target genes (CD36 and
      ADRP) by 43%, 43%, and 39%, respectively, with a reduction in liver TG
      concentration by 38% in 5 days. PPARgamma2 knockdown also reduced mRNAs in
      lipogenic genes (fatty-acid-synthase, stearoyl-CoA desaturase 1, acetyl-CoA
      carboxylase 1) without alteration of SREBP-1c mRNA. PPARgamma2 knockdown reduced
      mRNAs in genes related to inflammation (CD68, interleukin-1beta, tumor necrosis
      factor-alpha, and monocyte chemoattractant protein-1). In conclusion, saturated
      fatty acid-rich oil induced fatty liver in mice, and this was triggered initially
      by an increase in PPARgamma2 protein in the liver, which led to increased
      expression of lipogenic genes. Inactivation of PPARgamma2 may improve fatty liver
      induced by HF saturated fat.

PMID- 20801632
TI  - Dietary soy and tea mitigate chronic inflammation and prostate cancer via
      NFkappaB pathway in the Noble rat model.
AB  - Chronic inflammation and nuclear factor-kappa B (NFkappaB) have been implicated
      in prostate cancer development; thus, dietary factors that inhibit NFkappaB may
      serve as effective chemo-preventative agents. Prostate cancer risk is
      significantly lower in Asian countries compared to the United States, which has
      prompted interest in the potential chemopreventative action of Asian dietary
      components such as soy and green tea. This study examined the effects of dietary
      soy and tea on NFkappaB activation and inflammation in vivo using a hormone
      induced rat model for prostate cancer. Male Noble rats implanted with estradiol
      and testosterone were divided into 4 dietary groups: control, soy, tea, or
      soy+tea. NFkappaB activation and inflammatory cytokines were measured post
      implantation. The combination of soy and tea suppressed NFkappaB p50 binding
      activity and protein levels via induction of IkappaBalpha. Soy and tea also
      decreased prostate inflammatory infiltration, increased Bax/BcL2 ratio and
      decreased protein expression of tumor necrosis factor-alpha, interleukin (IL)-6
      and IL-1beta compared to control. Soy and tea attenuated prostate malignancy by
      decreasing prostate hyperplasia. These effects were not apparent in groups
      treated with soy or tea alone. The ongoing in vivo studies thus far suggest that
      combination of foods, such as soy and tea, may inhibit hormone-induced
      proinflammatory NFkappaB signals that contribute to prostate cancer development.

PMID- 20801633
TI  - Reduced expression of SIRT1 is associated with diminished glucose-induced insulin
      secretion in islets from calorie-restricted rats.
AB  - Alterations in food intake such as caloric restriction modulate the expression of
      SIRT1 and SIRT4 proteins that are involved in pancreatic beta-cell function.
      Here, we search for a possible relationship between insulin secretion and the
      expression of SIRT1, SIRT4, PKC and PKA in islets from adult rats submitted to CR
      for 21 days. Rats were fed with an isocaloric diet (CTL) or received 60% (CR) of
      the food ingested by CTL. The dose-response curve of insulin secretion to glucose
      was shifted to the right in the CR compared with CTL islets (EC(50) of 15.1+/
      0.17 and 10.5+/-0.11 mmol/L glucose). Insulin release by the depolarizing agents
      arginine and KCl was reduced in CR compared with CTL islets. Total islet insulin
      content and glucose oxidation were also reduced in CR islets. Leucine-stimulated
      secretion was similar in both groups, slightly reduced in CR islets stimulated by
      leucine plus glutamine but higher in CR islets stimulated by ketoisocaproate
      (KIC). Insulin secretion was also higher in CR islets stimulated by carbachol,
      compared with CTL islets. No differences in the rise of cytosolic Ca(2+)
      concentrations stimulated by either glucose or KCl were observed between groups
      of islets. Finally, SIRT1, but not SIRT4, protein expression was lower in CR
      compared with CTL islets, whereas no differences in the expression of PKC and PKA
      proteins were observed. In conclusion, the lower insulin secretion in islets from
      CR rats was, at least in part, due to an imbalance between the expression of
      SIRT1 and SIRT4.

PMID- 20801634
TI  - Development of biocompatible SERS nanotag with increased stability by
      chemisorption of reporter molecule for in vivo cancer detection.
AB  - Biocompatible surface-enhanced Raman scattering (SERS) nanotag has been developed
      by chemisorption of novel Raman reporters on gold colloid. We modified our
      previously published best five reporter molecules (B2, B7, C3, C7 and C9) from
      triphenylmethine (TM) library using lipoic acid (LA) as a linker to covalently
      attach the reporters on gold colloid. Among these TM-LA molecules, B2LA showed
      the highest SERS signal intensity and stability over time. Further, time course
      SERS intensity of B2LA was compared with currently popular Raman reporter
      malachite green isothiocyanate (MGITC). The results demonstrated that signal
      intensity from B2LA was even stable over a period of one month. In vitro SERS
      screening was performed in cancer cell lines using B2LA containing nanotag
      conjugated with selective antibodies recognizing HER2 and EGFR cancer proteins.
      We found reasonably strong SERS signals from both HER2 and EGFR positive cells
      whereas no signal was measured from respective negative cells. Moreover, we
      successfully proved this recognition by cell imaging using fluorescein
      isothiocyanate (FITC) labeled antibody conjugated nanotag. Both SERS and cell
      imaging study further confirmed the selective binding of antibody conjugated
      nanotag to cancer cells over-expressing HER2 and EGFR. In addition, as a proof of
      concept, in vivo SERS measurement in a mouse model was carried out to detect the
      nanotag-anchored cancer cells that are subcutaneously injected to the animal.

PMID- 20801635
TI  - Affinity sensor using 3-aminophenylboronic acid for bacteria detection.
AB  - Boronic acid that can reversibly bind to diols was used to detect bacteria
      through its affinity binding reaction with diol-groups on bacterial cell walls. 3
      aminophenylboronic acid (3-APBA) was immobilized on a gold electrode via a self
      assembled monolayer. The change in capacitance of the sensing surface caused by
      the binding between 3-APBA and bacteria in a flow system was detected by a
      potentiostatic step method. Under optimal conditions the linear range of
      1.5*10(2)-1.5*10(6) CFU ml(-1) and the detection limit of 1.0*10(2) CFU ml(-1)
      was obtained. The sensing surface can be regenerated and reused up to 58 times.
      The method was used for the analysis of bacteria in several types of water, i.e.,
      bottled, well, tap, reservoir and wastewater. Compared with the standard plate
      count method, the results were within one standard deviation of each other. The
      proposed method can save both time and cost of analysis. The electrode modified
      with 3-APBA would also be applicable to the detection of other cis-diol
      containing analytes. The concept could be extended to other chemoselective
      ligands, offering less expensive and more robust affinity sensors for a wide
      range of compounds.

PMID- 20801636
TI  - Biomolecular plasmonics for quantitative biology and nanomedicine.
AB  - Free electrons in a noble metal nanoparticle can be resonantly excited, leading
      to their collective oscillation termed as a surface plasmon. These surface
      plasmons enable nanoparticles to absorb light, generate heat, transfer energy,
      and re-radiate incident photons. Creative designs of nanoplasmonic optical
      antennae (i.e. plasmon resonant nanoparticles) have become a new foundation of
      quantitative biology and nanomedicine. This review focuses on the recent
      developments in dual-functional nanoplasmonic optical antennae for label-free
      biosensors and nanoplasmonic gene switches. Nanoplasmonic optical antennae,
      functioning as biosensors to significantly enhance biochemical-specific spectral
      information via plasmon resonance energy transfer (PRET) and surface-enhanced
      Raman spectroscopy (SERS), are discussed. Nanoplasmonic optical antennae,
      functioning as nanoplasmonic gene switches to enable spatiotemporal regulation of
      genetic activity, are also reviewed. Nanoplasmonic molecular rulers and
      integrated photoacoustic-photothermal contrast agents are also described.

PMID- 20801637
TI  - Evaluation of two self-referent foot health instruments.
AB  - Two foot health inventories, the Foot Function Index and the Foot Health Status
      Questionnaire, are evaluated in terms of the developmental procedures used to
      create them. Both instruments have a number of deficiencies with regard to the
      initial stages of their development and with their purported reliability and
      validity. These deficiencies indicate that these instruments may have limited
      value and that in both clinical and research situations they may not produce
      sufficiently accurate or informative results. Given that these instruments are
      typical of many self-referent instruments used in health contexts, clinicians and
      researchers should carefully evaluate the credentials of such instruments before
      using them. This article demonstrates how such evaluations might be conducted.

PMID- 20801638
TI  - Machines that learn to segment images: a crucial technology for connectomics.
AB  - Connections between neurons can be found by checking whether synapses exist at
      points of contact, which in turn are determined by neural shapes. Finding these
      shapes is a special case of image segmentation, which is laborious for humans and
      would ideally be performed by computers. New metrics properly quantify the
      performance of a computer algorithm using its disagreement with 'true'
      segmentations of example images. New machine learning methods search for
      segmentation algorithms that minimize such metrics. These advances have reduced
      computer errors dramatically. It should now be faster for a human to correct the
      remaining errors than to segment an image manually. Further reductions in human
      effort are expected, and crucial for finding connectomes more complex than that
      of Caenorhabditis elegans.

PMID- 20801639
TI  - Cellular structural biology.
AB  - While we appreciate the complexity of the intracellular environment as a general
      property of every living organism, we collectively lack the appropriate tools to
      analyze protein structures in a cellular context. In-cell NMR spectroscopy
      represents a novel biophysical tool to investigate the conformational and
      functional characteristics of biomolecules at the atomic level inside live cells.
      Here, we review recent in-cell NMR developments and provide an outlook towards
      future applications in prokaryotic and eukaryotic cells. We hope to thereby
      emphasize the usefulness of in-cell NMR techniques for cellular studies of
      complex biological processes and for structural analyses in native environments.

PMID- 20801640
TI  - Downregulation of miR-21 modulates Ras expression to promote apoptosis and
      suppress invasion of Laryngeal squamous cell carcinoma.
AB  - MiRNAs are small, noncoding RNA molecules that emerge as important regulators of
      cancer-related processes. The miR-21 microRNA is overexpressed in a wide variety
      of cancers and has been causally related to cellular proliferation and apoptosis.
      In this study, we found that miR-21 is overexpressed in Laryngeal squamous cell
      carcinoma (LSCC) and correlated with advanced stage. Inhibition of miR-21 by
      antisense oligonucleotides (ASO) led to decreased protein level of Ras and
      profound suppression of cell proliferation and invasion. Hep-2 cells exposed to
      miR-21 ASO exhibited cell cycle arrest at G1 phase and increased apoptosis.
      Furthermore, growth of LSCC xenograft tumours was significantly suppressed by
      repeated injection of ASO-miR-21 lentivirus and the Ras protein expression in
      LSCC xenograft tumours was also downregulate by ASO-miR-21. Taken together, our
      data suggest that miR-21 may play an oncogenic role in the cellular processes of
      LSCC and represent a novel target for effective therapies.

PMID- 20801641
TI  - Expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of
      metalloproteinases 1 (TIMP-1) by colorectal cancer cells and adjacent stroma
      cells--associations with histopathology and patients outcome.
AB  - AIM: To elucidate cellular features accountable for colorectal cancers' (CRC)
      capability to invade normal tissue and to metastasize, we investigated the level
      of the collagenase matrix metalloproteinase 9 (MMP-9) and its physiological
      inhibitor tissue inhibitor of metalloproteinases 1 (TIMP-1) in cancer cells and
      supporting stroma cells of CRC. METHODS: Immunoreactivity of MMP-9 and TIMP-1 by
      carcinoma cells, lymphocytes and fibroblasts in archival specimens of paraffin
      embedded primary tumours were retrospectively associated with outcome in 340
      consecutive patients completely resected for CRC stages II-IV and subsequently
      treated with adjuvant 5-fluorouracil. RESULTS: Expression of MMP-9 by carcinoma
      cells was demonstrated in 9% of specimens without association to recurrence free
      survival (RFS) (HR = 1.0; 95% CI: 0.6-1.8; P = 0.9) or overall survival (OS) (HR
      = 0.9; 95% CI: 0.5-1.6; P = 0.6). TIMP-1 expression by carcinoma cells, which
      appeared in 64% of the specimens, was inversely related with RFS (HR = 1.3; 95%
      CI: 0.9-1.8; P = 0.08) and OS (HR = 1.5; 95% CI: 1.1-2.1; P = 0.02). Expression
      of TIMP-1 by fibroblasts at the invasive border was directly related to RFS (HR =
      0.7; 95% CI: 0.6-0.9; P = 0.02) and OS (HR = 0.7; 95% CI: 0.6-1.0; P = 0.05).
      Expression of MMP-9 by lymphocytes correlated significantly with the degree of
      peritumoural inflammation (P = 0.02) but not with RFS (HR = .9; 95% CI: 0.7-1.1;
      P = 0.2) or OS (HR = 0.8; 95% CI: 0.7-1.0; P = 0.07). CONCLUSION: TIMP-1 in
      cancer cells is associated with poor prognosis independent of its function as
      inhibitor of MMP-9. MMP-9 and TIMP-1 are important mediators of the host-cancer
      cell interaction in the tumour microenvironment with significant influence on the
      histopathology and on prognosis of CRC.

PMID- 20801642
TI  - Four and a half LIM protein 2 (FHL2) negatively regulates the transcription of E
      cadherin through interaction with Snail1.
AB  - E-cadherin is a hallmark of epithelial-mesenchymal transition (EMT), which plays
      a crucial role in cancer metastasis. We previously demonstrated that four and a
      half LIM protein 2 (FHL2) inhibited E-cadherin expression and promoted invasive
      potential and EMT in colon cancer. Here, we aim to further define the mechanism
      underlying the inhibition of E-cadherin by FHL2 in colon cancer. The expression
      profiles of FHL2 and Snail1 were first observed by Western blot,
      immunofluorescence and immunohistochemistry. We found that both the protein level
      and the cellular localisation of Snail1 were quite similar to FHL2 in colon
      cancer; reciprocal co-immunoprecipitation assay showed that FHL2 was able to bind
      Snail1 and its intact structure was required. The expression of FHL2 was
      positively correlated to Snail1 while negatively to E-cadherin and phospho
      Snail1. FHL2 over-expression induced the accumulation of Snail1 in the nucleus.
      Moreover, dual luciferase assay revealed that FHL2 over-expression decreased
      while FHL2 siRNA increased the transcriptional activities of two E-cadherin
      promoter constructs which contained E-box sites (Snail1-binding elements).
      Mutation of E-boxes increased the transcriptional activities and FHL2 expression
      was involved in the function of mutation. These results suggested that FHL2
      negatively regulated E-cadherin transcriptional activity through interaction with
      Snail1. Our study established a novel regulatory function of FHL2 and revealed a
      potential mechanism on promoting the process of EMT.

PMID- 20801643
TI  - Bioluminescence imaging correlates with tumor progression in an orthotopic mouse
      model of lung cancer.
AB  - BACKGROUND AND OBJECTIVES: To determine whether bioluminescence imaging of human
      lung cancer cells growing in an orthotopic murine model provides a sensitive tool
      for monitoring tumor progression in athymic nude mice. METHODS: Human lung cancer
      (A549) cells were stably transfected with the firefly luciferase gene and
      inoculated into the right lung of athymic nude mice. Seven days after inoculation
      tumor growth was evaluated using the Kodak in-vivo Imaging System FX and
      continued to be monitored on a weekly basis. RESULTS: In duplicate experiments,
      human lung cancer tumors formed in 90% of animal's injected orthotopically. The
      mean intensity of the bioluminescence signal emitted from the lung cancer cells
      increased logarithmically during the course of study. Mice with positive
      bioluminescence signaling had confirmed tumors by microscopic histological
      analysis. Bioluminescence activity had a strong correlation with the tumor volume
      as determined histologically. CONCLUSIONS: Bioluminescence intensity directly
      correlates with tumor volume and therefore offers a reliable approach for
      detecting and monitoring the growth of human lung cancer cells in orthotopic
      murine models.

PMID- 20801644
TI  - Succinic acid production by Actinobacillus succinogenes using hydrolysates of
      spent yeast cells and corn fiber.
AB  - The enzymatic hydrolysate of spent yeast cells was evaluated as a nitrogen source
      for succinic acid production by Actinobacillus succinogenes NJ113, using corn
      fiber hydrolysate as a carbon source. When spent yeast cell hydrolysate was used
      directly as a nitrogen source, a maximum succinic acid concentration of 35.5 g/l
      was obtained from a glucose concentration of 50 g/l, with a glucose utilization
      of 95.2%. Supplementation with individual vitamins showed that biotin was the
      most likely factor to be limiting for succinic acid production with spent yeast
      cell hydrolysate. After supplementing spent yeast cell hydrolysate and 90 g/l of
      glucose with 150 MUg/l of biotin, cell growth increased 32.5%, glucose
      utilization increased 37.6%, and succinic acid concentration was enhanced 49.0%.
      As a result, when biotin-supplemented spent yeast cell hydrolysate was used with
      corn fiber hydrolysate, a succinic acid yield of 67.7% was obtained from 70.3 g/l
      of total sugar concentration, with a productivity of 0.63 g/(l h). Our results
      suggest that biotin-supplemented spent yeast cell hydrolysate may be an
      alternative nitrogen source for the efficient production of succinic acid by A.
      succinogenes NJ113, using renewable resources.

PMID- 20801645
TI  - Expression of bacterial levanase in yeast enables simultaneous saccharification
      and fermentation of grass juice to bioethanol.
AB  - This study demonstrates use of recombinant yeast to simultaneously saccharify and
      ferment grass juice (GJ) to bioethanol. A modified Bacillus subtilis levanase
      gene (sacC) in which the native bacterial signal sequence was replaced with a
      yeast alpha-factor domain, was synthesised with yeast codon preferences and
      transformed into Saccharomyces cerevisiae (strain AH22) using the expression
      vector pMA91. AH22:psacC transformants secreted sacCp as an active, hyper
      glycosylated (>180 kDa) protein allowing them to utilise inulin (beta[2-1] linked
      fructose) and levan (beta[2-6] linkages) as growth substrates. The control
      (AH22:pMA91) strain, transformed with empty plasmid DNA was not able to utilise
      inulin or levan. When cultured on untreated GJ levels of growth and bioethanol
      production were significantly higher in experiments with AH22:psacC than with
      AH22:pMA91. Bioethanol yields from AH22:psacC grown on GJ (32.7[+/-4] mg mL(-1))
      compared closely to those recently achieved (Martel et al., 2010) using
      enzymatically pre-hydrolysed GJ (36.8[+/-4] mg mL(-1)).

PMID- 20801646
TI  - Upgrading of crude algal bio-oil in supercritical water.
AB  - We determined the influence of a Pt/C catalyst, high-pressure H2, and pH on the
      upgrading of a crude algal bio-oil in supercritical water (SCW). The SCW
      treatment led to a product oil with a higher heating value (~42 MJ/kg) and lower
      acid number than the crude bio-oil. The product oil was also lower in O and N and
      essentially free of sulfur. Including the Pt/C catalyst in the reactor led to a
      freely flowing liquid product oil with a high abundance of hydrocarbons. Overall,
      many of the properties of the upgraded oil obtained from catalytic treatment in
      SCW are similar to those of hydrocarbon fuels derived from fossil fuel resources.
      Thus, this work shows that the crude bio-oil from hydrothermal liquefaction of a
      microalga can be effectively upgraded in supercritical water in the presence of a
      Pt/C catalyst.

PMID- 20801647
TI  - Conditioning of dilute-acid pretreated corn stover hydrolysate liquors by
      treatment with lime or ammonium hydroxide to improve conversion of sugars to
      ethanol.
AB  - Dilute-acid pretreatment of lignocellulosic biomass enhances the ability of
      enzymes to hydrolyze cellulose to glucose, but produces many toxic compounds that
      inhibit fermentation of sugars to ethanol. The objective of this study was to
      compare the effectiveness of treating hydrolysate liquor with Ca(OH)2 and NH4OH
      for improving ethanol yields. Corn stover was pretreated in a pilot-scale reactor
      and then the liquor fraction (hydrolysate) was extracted and treated with various
      amounts of Ca(OH)2 or NH4OH at several temperatures. Glucose and xylose in the
      treated liquor were fermented to ethanol using a glucose-xylose fermenting
      bacteria, Zymomonas mobilis 8b. Sugar losses up to 10% occurred during treatment
      with Ca(OH)2, but these losses were two to fourfold lower with NH4OH treatment.
      Ethanol yields for NH4OH-treated hydrolysate were 33% greater than those achieved
      in Ca(OH)2-treated hydrolysate and pH adjustment to either 6.0 or 8.5 with NH4OH
      prior to fermentation produced equivalent ethanol yields.

PMID- 20801648
TI  - Swine manure/crude glycerol co-liquefaction: physical properties and chemical
      analysis of bio-oil product.
AB  - The aim of this work was to investigate the principal structural and physico
      chemical changes of bio-oils associated with liquefaction of swine manure with
      crude glycerol and its key fraction, free fatty acids. Bio-oils have been
      obtained from liquefaction processes at 340  degrees C. They were subjected to
      various physico-chemical characterization methods. FTIR data indicated a
      reduction in aliphatic structures and an increase in more oxidized and, probably,
      more polycondensed aromatic components resulting from the addition of crude
      glycerol to swine manure. GC-MS data indicated that the addition of crude
      glycerol facilitated the esterification reaction in sub-critical water to convert
      organic acids contained in bio-oil into various kinds of esters. The dynamic
      viscosity of bio-oil decreased dramatically by adding crude glycerol into the
      swine manure.

PMID- 20801649
TI  - Parallel synthesis and anti-inflammatory activity of cyclic peptides
      cyclosquamosin D and Met-cherimolacyclopeptide B and their analogs.
AB  - We report the parallel synthesis of two natural cyclopeptides, isolated from the
      seeds of Annona squamosa, cyclosquamosin D (A1), and Met-cherimolacyclopeptide B
      (B) and their analogs. All of the compounds were screened for anti-inflammatory
      activity by evaluating their inhibitory effects on the production of pro
      inflammatory cytokines using the lipopolysaccharide stimulated macrophage J774A.1
      cell line. Compounds having significant anti-inflammatory activity in suppressing
      the secretion of IL-6 and TNF-alpha have been identified, some of which exhibit
      activity superior to that observed with the natural products.

PMID- 20801650
TI  - 6-Alkoxyisoindolin-1-one based dopamine D2 partial agonists as potential
      antipsychotics.
AB  - A series of 6-alkoxyisoindolin-1-ones with a magic shotgun pharmacological
      profile are presented as potential antipsychotics. The in vitro pharmacological
      profile includes D(2) partial agonism (30-55%), 5-HT(1A) partial agonism (60
      90%), and 5-HT(2A) antagonism. Selected compounds in this series displayed good
      in vivo activity and potency.

PMID- 20801651
TI  - Heterobiaryl and heterobiaryl ether derived M5 positive allosteric modulators.
AB  - This Letter describes a chemical lead optimization campaign directed at
      VU0238429, the first M(5)-preferring positive allosteric modulator (PAM),
      discovered through analog work around VU0119498, a pan G(q) mAChR M(1), M(3),
      M(5) PAM. An iterative parallel synthesis approach was employed to incorporate
      basic heterocycles to improve physiochemical properties.

PMID- 20801652
TI  - Bis-alkylamine quindolone derivatives as new antimalarial leads.
AB  - Quindolone derivatives, designed to target the malaria parasite digestive vacuole
      and heme detoxification pathway, have been synthesized by reaction with 2-chloro
      N,N-diethylethanamine. This reaction gave N,O-, N,N- and O-alkylated products
      containing one or two basic side-chains. The compounds were evaluated for
      antiplasmodial activity against the chloroquine-resistant Plasmodium falciparum
      W2 strain and for cytotoxicity in HepG2 A16 hepatic cells. By incorporating
      alkylamine side chains and chlorine atoms in the quindolone nucleus we
      transformed the inactive tetracyclic parent quindolones into moderate or highly
      active and selective antimalarial compounds. The most active and selective
      compound, 5c, showed an IC(50)=51 nM for P. falciparum and a selectivity ratio of
      98.

PMID- 20801653
TI  - Novel macrocyclic HCV NS3 protease inhibitors derived from alpha-amino cyclic
      boronates.
AB  - A novel series of P2-P4 macrocyclic HCV NS3/4A protease inhibitors with alpha
      amino cyclic boronates as warheads at the P1 site was designed and synthesized.
      When compared to their linear analogs, these macrocyclic inhibitors exhibited a
      remarkable improvement in cell-based replicon activities, with compounds 9a and
      9e reaching sub-micromolar potency in replicon assay. The SAR around alpha-amino
      cyclic boronates clearly established the influence of ring size, chirality and of
      the substitution pattern. Furthermore, X-ray structure of the co-crystal of
      inhibitor 9a and NS3 protease revealed that Ser-139 in the enzyme active site
      traps boron in the warhead region of 9a, thus establishing its mode of action.

PMID- 20801654
TI  - Effect of unsaturation in fatty acids on the binding and oxidation by
      myeloperoxidase: ramifications for the initiation of atherosclerosis.
AB  - Oxidation of low density lipoproteins (LDL) in the presence of myeloperoxidase
      and subsequent uptake of the oxidized LDL by specialized receptors on macrophages
      has been suggested as an initiating event of atherosclerosis. Oxidized fatty acid
      chains within the glycerophospholipids of LDL have been implicated as the
      recognition feature by the receptors. The ability of three fatty acids (oleic,
      linoleic, and arachidonic acids) typically contained in the lipid portion of the
      glycerophospholipids to bind and be oxidized by myeloperoxidase was measured by
      spectroscopically observing interactions of the lipids with the heme prosthetic
      group of the enzyme. As unsaturation increases in the lipid chain,
      myeloperoxidase binds and oxidizes the fatty acid more readily, as measured by
      K(D), K(M), and k(cat). A possible mechanism of the free radical oxidation by
      myeloperoxidase is discussed.

PMID- 20801655
TI  - 2-, 3-, and 4-(1-Oxo-1H-2,3-dihydroisoindol-2-yl)benzoic acids and their
      corresponding organotin carboxylates: synthesis, characterization, fluorescent,
      and biological activities.
AB  - Three novel organotin complexes with general formula Sn(OH)(bz)(2)L (bz = benzyl,
      HL = 2-, 3-, or 4-(1-oxo-1H-2,3-dihydroisoindol-2-yl)benzoic acid) and one of
      their ligands were prepared and characterized. In vitro antifungal and
      antibacterial activities of these complexes and ligands were investigated with
      the representative strains of Candida albicans, Staphylococcus aureus,
      Escherichia coli, and Pseudomonas aeruginosa. Their fluorescence properties have
      also been discussed.

PMID- 20801656
TI  - A new NF-kappaB inhibitor based on the amino-epoxyquinol core of DHMEQ.
AB  - The amino-epoxyquinols 6a and 6b were synthesized as soluble derivatives of an NF
      kappaB inhibitor DHMEQ (1). In spite of the opposite configuration from 1, 6b
      rather than 6a affected the deactivation of NF-kappaB, based on NO secretion and
      MALDI-TOF MS analysis. It was indicated that 6b inhibited the activation by
      different manner from that of 1.

PMID- 20801658
TI  - Low vision affects dynamic stability of gait.
AB  - The objective of this study was to demonstrate specific differences in gait
      patterns between those with and without a visual impairment. We performed a
      biomechanical analysis of the gait pattern of young adults (27 +/- 13 years old)
      with a visual impairment (n=10) in an uncluttered environment and compared it to
      the gait pattern of age matched controls (n=20). Normally sighted adults were
      tested in a full vision and no vision condition. Differences are found in gait
      between both groups and both situations. Adults with a visual impairment walked
      with a shorter stride length (1.14 +/- 0.21m), less trunk flexion (4.55 +/- 5.14
      degrees ) and an earlier plantar foot contact at heel strike (1.83 +/- 3.49
      degrees ) than sighted individuals (1.39 +/- 0.08 m; 11.07 +/- 4.01 degrees ;
      5.10 +/- 3.53 degrees ). When sighted individuals were blindfolded (no vision
      condition) they showed similar gait adaptations as well as a slower walking speed
      (0.84 +/- 0.28 ms(-1)), a lower cadence (96.88 +/- 13.71 steps min(-1)) and
      limited movements of the hip (38.24 +/- 6.27 degrees ) and the ankle in the
      saggital plane (-5.60 +/- 5.07 degrees ) compared to a full vision condition
      (1.27 +/- 0.13 ms(-1); 110.55 +/- 7.09 steps min(-1); 45.32 +/- 4.57 degrees ; 
      16.51 +/- .59 degrees ). Results showed that even in an uncluttered environment
      vision is important for locomotion control. The differences between those with
      and without a visual impairment, and between the full vision and no vision
      conditions, may reflect a more cautious walking strategy and adaptive changes
      employed to use the foot to probe the ground for haptic exploration.

PMID- 20801659
TI  - Paraspinal malignant ossifying fibromyxoid tumor with spinal involvement.
AB  - Ossifying fibromyxoid tumors (OFT), first described in 1989 by Enzinger et al.,
      are rare lesions; malignant OFT (MOFT) are even rarer. We report a large
      recurrent paraspinal MOFT invading the spine and causing epidural compression in
      a 70-year-old male, despite prior debulking and radiotherapy. Paraspinal
      involvement of these tumors has been reported only twice before. We describe its
      imaging, pathology, and also review the pertinent literature.

PMID- 20801657
TI  - Transcription by the numbers redux: experiments and calculations that surprise.
AB  - The study of transcription has witnessed an explosion of quantitative effort both
      experimentally and theoretically. In this article we highlight some of the
      exciting recent experimental efforts in the study of transcription with an eye to
      the demands that such experiments put on theoretical models of transcription.
      From a modeling perspective, we focus on two broad classes of models: the so
      called thermodynamic models that use statistical mechanics to reckon the level of
      gene expression as probabilities of promoter occupancy, and rate-equation
      treatments that focus on the temporal evolution of the activity of a given
      promoter and that make it possible to compute the distributions of messenger RNA
      and proteins. We consider several appealing case studies to illustrate how
      quantitative models have been used to dissect transcriptional regulation.

PMID- 20801660
TI  - Responsive Mn(II) complexes for potential applications in diagnostic Magnetic
      Resonance Imaging.
AB  - The investigation of new Mn(II)-based MRI/Molecular Imaging probes responsive to
      the enzyme tyrosinase for potential diagnostic applications is herein described.
      The expression of the enzyme tyrosinase, an oxidoreductase, is up-regulated in
      melanoma cancer cells. Three novel ligands (L(1), L(2) and L(3)) were designed as
      modified acyclic polyaminocarboxylate chelates by introducing an l-tyrosine
      residue in place of an aminoacetate unit. The corresponding Mn(II) complexes were
      fully characterised by (1)H NMR relaxometric techniques in aqueous media. The
      responsive activity towards the expression of tyrosinase was then assessed by
      monitoring the (1)H 1/T(1) relaxivity changes during incubation experiments in
      buffered solutions containing tyrosinase at different concentrations and in
      B16F10 melanoma cell homogenate. New insight on the mechanism of action of these
      systems was gained by measuring the magnetic field dependence of the relaxivity
      and ESR spectra of the incubated solutions. The systems developed showed
      responsive activity to tyrosinase with a relaxation enhancement spanning from 50%
      (MnL(1)) to 350% (MnL(3)) which augurs well for the development of diagnostic
      probes to detect melanoma cancer.

PMID- 20801661
TI  - A fluorescein-containing, small-molecule, water-soluble receptor for cytosine
      free bases.
AB  - In this study, we synthesized small-molecule, water-soluble, fluorescein
      containing ureido compounds 6 and 8 as target receptors for cytosine free bases
      and then investigated the binding of cytosine free bases with the receptors using
      (15)N NMR spectroscopy and partially labeled cytosine-2,4-(13)C-1,3,4-(15)N
      cytosine. Binding with the receptor 6a (the disodium form of 6) caused the
      chemical shift of the nitrogen atom of the amino group of cytosine to move
      downfield; binding of the receptor 8a (the disodium form of 8), which is
      possessing no corresponding aryl nitrogen atom, had no effect on this signal.
      Fluorescence spectroscopy revealed that binding of cytosine and its derivatives
      led to quenching of the fluorescence of receptor 6a; in contrast, the quenching
      of receptor 8a was only slightly affected by cytosine. Because the fluorescence
      of 6a was not quenched by either deoxycytidine or uracil, it appears that this
      receptor is a specific for cytosine among the DNA bases. We used the fluorescence
      of 6a to measure the apparent binding constants for various cytosine derivatives,
      including the anticancer prodrug 5-fluorocytosine. Receptor 6a is the first small
      molecule, water-soluble fluorescent receptor for the specific binding of cytosine
      free bases in aqueous solution.

PMID- 20801662
TI  - Structure-activity relationships in 1,4-benzodioxan-related compounds. 10. Novel
      alpha1-adrenoreceptor antagonists related to openphendioxan: synthesis,
      biological evaluation, and alpha1d computational study.
AB  - A series of novel openphendioxan analogues were synthesized and tested at
      alpha(1)-adrenoreceptor (AR) subtypes by binding and functional assays. The
      alpha(1d)-AR binding profile was also examined by means of 2D, 3D-QSAR together
      with docking studies. Multiple regression analysis suggested the relevance of
      adequate number of heteroatoms in the whole molecule and of passive membrane
      diffusion to enhance alpha(1d)-AR affinity. Docking simulations against a
      computational structural model of the biological target further proved this
      evidence and furnished support for chemiometric analysis, where polar,
      electrostatic, hydrophobic and shape effects of the ortho substituents in the
      phenoxy terminal, most likely governing ligand binding, helped the depiction of
      pharmacophore hypothesis for the examined ligands data set.

PMID- 20801663
TI  - Delphinidin, a dietary anthocyanidin in berry fruits, inhibits human glyoxalase
      I.
AB  - Glyoxalase I (GLO I) is the rate-limiting enzyme for detoxification of
      methylglyoxal (MG), a side-product of glycolysis, which is able to induce
      apoptosis. Since GLO I is known to be highly expressed in the most tumor cells
      and little in normal cells, inhibitors of this enzyme has been expected to be new
      anticancer drugs. Here, we examined the inhibitory abilities to the human GLO I
      of anthocyanidins, such as delphinidin, cyanidin and pelargonidin. Among them,
      delphinidin was found to have the most potent inhibitory effect on human GLO I.
      Also, only delphinidin-induced apoptosis in HL-60 cells in a dose- and time
      dependent manner. Furthermore, we determined a pharmacophore for delphinidin
      binding to the human GLO I by computational simulation analyses of the binding
      modes of delphinidin, cyanidin and pelargonidin to the enzyme hot spot. These
      results suggest that delphinidin could be a useful lead compound for the
      development of novel GLO I inhibitory anticancer drugs.

PMID- 20801664
TI  - Chalcone glycosides isolated from aerial parts of Brassica rapa L. 'hidabeni'
      suppress antigen-stimulated degranulation in rat basophilic leukemia RBL-2H3
      cells.
AB  - We isolated three chalcone glycosides along with other glycoside constituents
      from the aerial parts of Brassica rapa L. 'hidabeni' and examined the effects of
      these compounds on the antigen-stimulated degranulation in rat basophilic
      leukemia RBL-2H3 cells. Treatments with both 4'-O-beta-D-glucopyranosyl-4-hydroxy
      3'-methoxychalcone (C1) and 4'-O-beta-D-glucopyranosyl-3',4-dimethoxychalcone
      (C2) markedly inhibited antigen (Ag)-stimulated degranulation. To gain further
      insight into the inhibitory mechanisms by C1 and C2, we examined early
      intracellular signaling events, Ca(2+) mobilization and intracellular reactive
      oxygen species (ROS) production. Both C1 and C2 did not affect early
      intracellular signaling events but exhibited the suppression of intracellular ROS
      production through NADPH oxidase (NOX) inactivation. From these results, we
      proposed that the inhibitory effects of C1 and C2 on Ag-stimulated degranulation
      were mainly due to suppression of intracellular Ca(2+) elevation by suppression
      of intracellular ROS production through NOX inactivation. Our findings suggest
      that C1 and C2 would be beneficial to alleviate symptoms of type I allergy.

PMID- 20801665
TI  - Excitation function for deuteron induced nuclear reactions on natural ytterbium
      for production of high specific activity 177g Lu in no-carrier-added form for
      metabolic radiotherapy.
AB  - Deuteron-induced nuclear reactions for generation of no-carrier-added Lu
      radionuclides were investigated using the stacked-foil activation technique on
      natural Yb targets at energies up to E(d)=18.18 MeV. Excitation functions of the
      reactions (nat)Yb(d,xn)(169,170,171,172,173,174g,174m,176m,177g)Lu and
      (nat)Yb(d,pxn)(169,175,177)Yb have been measured, among them three ((169)Lu,
      (174m)Lu and (176m)Lu) are reported for the first time. The upper limit of the
      contamination from the long-lived metastable level (177m)Lu was evaluated too.
      Thick-target yields for all investigated radionuclides are calculated.

PMID- 20801666
TI  - Horizontal and vertical characterization of radionuclides and minerals in river
      sediments.
AB  - The natural radionuclide ((238)U, (232)Th and (40)K) contents and mineral
      characteristics have been analyzed for the different depth sediment samples of
      Ponnaiyar River with an aim of evaluating the radiation hazard and its relation
      to specific minerals. To know the complete radiological characteristics, the
      radiological indices have been calculated and compared with recommended values.
      In an FTIR study, the extinction coefficient and crystallinity index is
      calculated to find the relative distribution of major minerals and the
      crystallinity of quartz, respectively. Both horizontal and vertical distributions
      of radionuclides and major minerals are studied. Multivariate statistical
      analyses (cluster and factor) were carried out to determine the relationship
      between the radioactivity and the minerals. Statistical analyses suggest that the
      kaolinite is the major mineral to increase the level of radioactivity in the
      river sediments.

PMID- 20801667
TI  - Straight, semi-anatomic and anatomic TMJ implants: the influence of condylar
      geometry and bone fixation screws.
AB  - A 3D finite element model of in vitro intact and implanted mandibles with
      different temporomandibular joints (TMJ) was analyzed. Three TMJ implant
      geometries were assessed. The displacements, stress and strain fields on the
      condyle were obtained for both simulated cases. Strains were also assessed near
      the screws that fixate the implant to the mandible. The geometry of the mandible
      was obtained through 3D digitalization of a synthetic model. The TMJ implants
      studied were modelled considering a commercial implant which was also used to
      create semi-anatomic and anatomic implants that were analyzed and to assess the
      influence of the geometry. Numerical finite element models were built and the
      implants were positioned by an experienced orofacial surgeon. All implants were
      fixed by four screws which were placed in the same position on the mandible. The
      boundary conditions were simulated considering the support on the incisive tooth,
      the loads of the five most important muscular forces and a 5mm mouth aperture.
      This study indicates that the deformation on the intact mandible was similar when
      an anatomic implant was considered in the implanted mandible. However, the
      anatomic geometry presented some problems concerning the implant integrity due to
      geometric variations. The geometry of TMJ implant also played a role relatively
      to the screws structural integration and bone fixation. The geometry of TMJ
      implant defines the necessary number of screws and position in the mandible
      fixation.

PMID- 20801668
TI  - Multivesicular intrapericardial hydatidosis.

PMID- 20801669
TI  - Inactivation of several strains of Listeria monocytogenes attached to the surface
      of packaging material by Na-Chlorophyllin-based photosensitization.
AB  - This study was focused on the possibility to inactivate thermosensitive Listeria
      monocytogenes ATC(L3)C 7644 and thermoresistant 56 Ly strain by Na-Chlorophyllin
      (Na-Chl)-based photosensitization in vitro and on the surface of packaging.
      Comparative analysis of antimicrobial efficiency of photosensitization with
      conventional surface cleaning was performed. Data indicate that both Listeria
      strains, after incubation with Na-Chl and following illumination (lambda=400nm,
      20mWcm(-2)), were inactivated by 7 log in vitro. This treatment cleaned both
      Listeria strains from packaging surfaces. Comparative analysis indicates that
      washing with water diminishes pathogens by less than 1 log, 200ppm Na
      hypochlorite by 1.7 log, Na-Chl-based photosensitization by 4.5 log. Listeria
      biofilms were totally removed from the surface by photosensitization at higher
      photosensitizer concentrations and longer incubation times. In conclusion, both
      strains of L. monocytogenes can be effectively inactivated by photosensitization
      in vitro and on the surface of packaging. Listeria biofilms are susceptible to
      this treatment as well. Comparison of different surface decontamination
      treatments reveals that photosensitization is much more effective against both
      Listeria strains than washing with water or 200ppm Na-hypochlorite. Our data
      support the idea that Na-Chl-based photosensitization is an effective
      antimicrobial tool which may serve in the future for the development of human and
      environmentally friendly surface decontamination techniques.

PMID- 20801670
TI  - Acute effect of labile surfaces during core stability exercises in people with
      and without low back pain.
AB  - OBJECTIVE: The purpose of this study was to measure trunk muscle activity, whole
      body balance, and lumbar range of motion during core stability exercises in
      individuals with and without low back pain (LBP) on and off a labile surface.
      DESIGN: Descriptive cross-sectional study. SETTING: University laboratory.
      PARTICIPANTS: Ten individuals with chronic non-specific LBP and 10 matched
      control subjects. MAIN OUTCOME MEASURES: Bilateral trunk muscle activity was
      measured using surface electromyography (EMG); whole body balance was measured by
      quantifying the dispersion of the centre of pressure (CoP); lumbar range of
      motion (LROM) was measured with single-axis inclinometers. RESULTS: Individuals
      with LBP had adaptive recruitment patterns during the side-bridge and modified
      push-up exercises. CoP dispersion and LROM were not different between groups for
      any exercise. The labile surface did not change the difference between groups,
      and only increased muscle activity during the side-bridge (p<0.05). The labile
      surface increased LROM (p=0.35) and CoP dispersion (p<0.001) during the
      quadruped, decreased LROM during squats (p=0.05), and increased CoP dispersion
      during push-ups (p=0.04). CONCLUSION: Individuals with LBP exhibited adaptive
      trunk muscle activity levels while maintaining similar levels of balance and
      lumbar movement to healthy controls. Since research suggests no one mode of
      exercise is more beneficial in LBP rehabilitation, the practicality and safety of
      labile surfaces for LBP exercise rehabilitation must be questioned from this
      study.

PMID- 20801671
TI  - Optimal whole-body vibration settings for muscle strength and power enhancement
      in human knee extensors.
AB  - This study compared the effects of 6-week whole-body vibration (WBV) training
      programs with different frequency and peak-to-peak displacement settings on knee
      extensor muscle strength and power. The underlying mechanisms of the expected
      gains were also investigated. Thirty-two physically active male subjects were
      randomly assigned to a high-frequency/high peak-to-peak displacement group (HH;
      n=12), a low-frequency/low peak-to-peak displacement group (LL; n=10) or a sham
      training group (SHAM; n=10). Maximal voluntary isometric, concentric and
      eccentric torque of the knee extensors, maximal voluntary isometric torque of the
      knee flexors, jump performance, voluntary muscle activation, and contractile
      properties of the knee extensors were assessed before and after the training
      period. Significant improvement in knee extensor eccentric voluntary torque
      (P<0.01), knee flexor isometric voluntary torque (P<0.05), and jump performance
      (P<0.05) was observed only for HH group. Regardless of the group, knee extensor
      muscle contractile properties (P<0.05) were enhanced. No modification was
      observed for voluntary muscle activation or electrical activity of agonist and
      antagonist muscles. We concluded that high-frequency/high peak-to-peak
      displacement was the most effective vibration setting to enhance knee extensor
      muscle strength and jump performance during a 6-week WBV training program and
      that these improvements were not mediated by central neural adaptations.

PMID- 20801672
TI  - Crosstalk effect on surface electromyogram of the forearm flexors during a static
      grip task.
AB  - The fraction of crosstalk was examined from the surface EMG signals collected
      from digit- and wrist-dedicated flexors with a blind signal separation (BSS)
      algorithm. Six participants performed static power grip tasks in a neutral
      posture at four different exertion levels of 25%, 50%, 75%, and 100% MVC. The
      signals were collected from the flexor digitorum superficialis, flexor digitorum
      profundus, flexor carpi radialis, palmaris longus, and flexor carpi ulnaris using
      a bipolar electrode configuration. The percentage of root mean square (RMS) was
      used as an amplitude-based index of crosstalk by normalizing the signals
      including crosstalk to those excluding crosstalk by the BSS algorithm for each
      %MVC exertion. The peak R(2) value of a cross-correlation function was also
      calculated as a correlation-based index of crosstalk for a group of forearm
      flexors by force level and algorithm application. The fraction of crosstalk
      ranged from 32% to 50% in the wrist-dedicated flexors and from 11% to 25% in the
      digit-dedicated flexors. Since surface EMG signals had such high levels of
      crosstalk, reduction methods like the BSS algorithm should be employed, as the
      BSS significantly reduced crosstalk in the forearm flexors 33% over all muscles
      and exertion levels. Thus, it is recommended that BSS be utilized to reduce
      crosstalk for the digit- and wrist-dedicated flexors during gripping tasks.

PMID- 20801673
TI  - Two-year clinical evaluation of the Zilver vascular stent for symptomatic iliac
      artery disease.
AB  - PURPOSE: To evaluate the 2-year outcomes of safety and effectiveness for iliac
      artery stent placement and examine the effects of placement in the common iliac
      artery (CIA) and external iliac artery (EIA), the degree of initial stenosis, and
      patient gender on success. MATERIALS AND METHODS: Zilver vascular stents (Cook
      Inc., Bloomington, Indiana) were placed in 151 consecutive patients whose iliac
      arteries remained stenotic after percutaneous transluminal angioplasty (PTA).
      Success at 2 years was determined by patency, ankle-brachial index (ABI) scores,
      and Walking Impairment Questionnaire (WIQ) scores. RESULTS: Patency, ABI
      measurements, and WIQ scores showed improvement at 2 years, compared with
      preprocedure measurements. Kaplan-Meier estimate of overall patency at 2 years
      was 90% (n = 117). Significant improvement in ABI and WIQ scores was seen at 2
      years, compared with preprocedural values (P < .01). The 2-year overall success
      rate was 91%. The degree of initial stenosis, stent location, and patient gender
      did not affect the success of the Zilver stent (P = .65, P = .58, and P = .77).
      The Kaplan-Meier estimate of the probability of experiencing a major adverse
      event (MAE) related to the device or stent placement procedure by the 2-year
      follow-up was 2.7%. CONCLUSIONS: The Zilver vascular stent remains durable at 2
      years in regard to safety and clinical effectiveness, and is effective in the CIA
      and EIA both in male and female patients.

PMID- 20801674
TI  - C-arm CT-guided foam sclerotherapy for the treatment of gastric varices.
AB  - The authors describe here the use of foam sclerotherapy under C-arm computed
      tomography (CT) guidance for the treatment of gastric varices via balloon
      occluded retrograde transvenous obliteration in seven patients and percutaneous
      transhepatic obliteration in one patient. All gastric varices were occluded
      successfully after replacement of blood by foam, which was trapped in the gastric
      varices as shown by C-arm CT. It also helped reduce the amount of sclerosant, an
      issue that is associated with severe complications, such as hemolysis, allergy,
      acute respiratory distress syndrome, and others. Foam sclerotherapy under C-arm
      CT guidance is a promising tool in the therapeutic armamentarium against gastric
      varices.

PMID- 20801675
TI  - Testicular ischemia following endovascular infrarenal abdominal aortic aneurysm
      repair: a rare complication.

PMID- 20801676
TI  - Distal embolism of percutaneous arterial closure device resulting in critical
      limb ischemia.

PMID- 20801677
TI  - The safety and effectiveness of a curved needle for vertebral augmentation:
      comparison with traditional techniques.
AB  - PURPOSE: To evaluate the safety and effectiveness of a curved needle compared
      with traditional (noncurved needle) techniques in a large single-center
      experience. MATERIALS AND METHODS: This study was a retrospective analysis of 243
      consecutive vertebral augmentation procedures over a 17-month period. Curved
      needle procedures were compared with noncurved needle procedures for baseline
      clinical variables, complication rate, pain relief, and improvement in
      disability. Procedure duration and fluoroscopy time were compared between the two
      cohorts. RESULTS: Between curved needle and noncurved needle procedures, there
      were no statistically significant differences in the baseline clinical variables,
      fracture location, and fracture etiology. No complications were noted in either
      group. In both groups, there was a median improvement in the visual analog scale
      (VAS) score of 2.0 points (P = .62). More than 90% of procedures in both groups
      resulted in some pain improvement (P = .78). For both groups, the median
      improvement in disability on the Roland Morris Disability Questionnaire (RMDQ)
      was 4.0 points (P = .69). Approximately 70% of procedures in both groups resulted
      in improvement in disability (P = 1.00). In single-level cases, there were
      shorter procedure times (51.8 min +/- 2.7 vs 62.8 min +/- 2.2, P = .002) and
      shorter fluoroscopy times (P = .31) for curved needle procedures. CONCLUSIONS:
      The curved needle is as safe and effective as traditional vertebral augmentation
      techniques in treating the pain and disability related to vertebral compression
      fractures. Additionally, the curved needle is associated with shorter procedure
      duration and reduced fluoroscopy time.

PMID- 20801678
TI  - Antegrade access to the superficial femoral artery with ultrasound guidance:
      feasibility and safety.
AB  - PURPOSE: To evaluate the feasibility and safety of antegrade superficial femoral
      artery (SFA) access with the use of ultrasound (US) guidance. MATERIALS AND
      METHODS: One hundred consecutive patients (56% men) were prospectively enrolled,
      with a median age of 76 years. The SFA was punctured in antegrade fashion with a
      19-gauge needle with US guidance, followed by sheath placement. The time from
      local anesthesia until successful blood aspiration from the sheath was measured.
      At the end of the case, hemostasis was achieved with a closure device or by
      manual compression. All cases were followed with US for access complications.
      RESULTS: Antegrade arterial access was successful in all cases. The arterial
      sheath was successfully placed into the SFA in 98 of 100 patients. In 95 of 98,
      the sheath was inserted with US guidance only; additional fluoroscopy was needed
      in three cases. In two of 100 patients, the common femoral artery (CFA) was
      accessed, accidentally in one case and deliberately in the other because the SFA
      was considered too small. Both patients were excluded from further analysis. The
      median time for arterial access was 3.5 minutes (interquartile range, 3.1-6.2
      min). All complications directly related to vascular access were minor (16;
      15.68%): 10 pseudoaneurysms (10.2%; median diameter, 15 mm) and six hematomas
      (6.12%; median diameter, 31.5 mm). CONCLUSIONS: Antegrade puncture into the SFA
      with US guidance is feasible and fast. The rate of minor complications is similar
      to other reported series, but a direct comparison with other studies is difficult
      because study designs vary.

PMID- 20801679
TI  - Thermochemical ablation in an ex-vivo porcine liver model using acetic acid and
      sodium hydroxide: proof of concept.
AB  - PURPOSE: To establish proof of concept in tissue, using the exothermic
      neutralization reaction of acetic acid and sodium hydroxide in ex vivo porcine
      liver and to conduct an initial probe into the relationships of volume and
      concentration of reagents to temperatures and the areas affected. MATERIALS AND
      METHODS: A total of 0.5 mL or 2 mL of either 5 mole/L or 10 mole/L acid and base
      solutions was injected simultaneously into the periphery of ex vivo porcine liver
      using a prototype injection device. Tissue temperature was recorded at the
      injection site for 5 minutes using a type T thermocouple temperature probe
      inserted parallel to and near the tip of the injection device. The injections
      were repeated for infrared thermography, and ablated tissues were sectioned
      quickly and imaged. A gross photograph was captured in each case to provide
      correlation. RESULTS: Maximum temperatures (17 degrees C baseline) ranged from
      42.1 degrees  +/- alpha3.34 degrees C to 61.7 degrees  +/- alpha10 degrees C
      (P<.05) when injecting 0.5 mL of 5 mole/L reactants and 2 mL of 10 mole/L
      reactants, respectively. The maximum temperature measured by infrared imaging
      ranged from 31 degrees -47 degrees C. Using an infrared viewing scale from 19
      degrees -40 degrees C, the cross-sectional area of tissue heating above baseline
      measured from 1.07 cm(2)+/- 0.45 to 4.95 cm(2)+/- 0.28 (P <05). CONCLUSIONS: The
      reaction of acetic acid and sodium hydroxide releases significant heat energy at
      the site of injection, and histologic changes are consistent with coagulation
      necrosis. Increased reagent concentration and volume were associated with larger
      temperature changes and larger areas of hyperthermia at gross pathology and
      infrared imaging.

PMID- 20801680
TI  - Therapeutic options for carotid in-stent restenosis: review of the literature.
AB  - To critically evaluate published evidence on therapeutic options for in-stent
      restenosis (ISR) after carotid artery stent (CAS) placement, a systematic
      analysis of studies reporting interventions for ISR after CAS placement was
      conducted. In total 20 studies were found, describing 100 interventions after
      carotid ISR in 96 patients. The interventions most performed were repeat
      percutaneous transluminal angioplasty (PTA; n = 54), repeat CAS placement (n =
      31), and carotid endarterectomy with stent removal (n = 9). No periprocedural
      complications were identified in any of the studies evaluated. Recurrent
      restenosis after intervention for ISR occurred in 12 of 84 cases (14%). All 12
      patients received tertiary treatment. Two patients developed a third recurrence
      and eventually disabling stroke, one of whom died. In the other 10 interventions,
      no further follow-up was described. In conclusion, several treatment strategies
      for ISR after CAS placement have been reported, with acceptable short-term
      results. The quality of the currently available data is still limited by the
      variability of results and study designs. Therefore, no recommendation can be
      made for any specific therapy. This argues for better study design and more
      consistency of reporting standards.

PMID- 20801681
TI  - Transcatheter N-butyl cyanoacrylate embolization of pseudoaneurysms.
AB  - PURPOSE: To report clinical experience with N-butyl cyanoacrylate (NBCA) for
      embolization of pseudoaneurysms at various locations. MATERIALS AND METHODS:
      Retrospective study of patients with pseudoaneurysms treated with NBCA over a 4
      year period was conducted. Seventeen consecutive patients were evaluated,
      including three women and 14 men ranging in age from 25 to 77 years (mean, 60.6
      y). NBCA was the only embolic agent used in 15 patients; in two patients, a
      liquid coil and a microcoil were placed before administration of NBCA. NBCA was
      mixed with iodized oil in a 1:3 ratio to control its polymerization time and to
      make it radiopaque. Diagnostic angiography and embolization were performed at the
      same session. Embolized sites included gastrointestinal tract (n = 6), spleen (n
      = 5), liver (n = 2), kidney (n = 1), chest (n = 1), oral cavity (n = 1), and
      buttock (n = 1). RESULTS: NBCA embolization was successful in 16 of 17 patients
      (94%), with complete occlusion of pseudoaneurysms. In one patient with a
      gastroduodenal artery stump pseudoaneurysm, NBCA embolization failed, and a stent
      graft (8 mm/40 mm) was placed in the hepatic artery, excluding the pseudoaneurysm
      and preserving the hepatic artery. No major complications occurred, and there
      were no recurrences of pseudoaneurysms. CONCLUSIONS: NBCA embolization was an
      effective method for the treatment of pseudoaneurysms.

PMID- 20801682
TI  - Endovascular preservation of full pelvic circulation with external iliac-to
      internal iliac artery "cross-stenting" in patients with aorto-iliac aneurysms.
AB  - Common iliac artery (CIA) aneurysms that extend into the iliac bifurcation and
      internal iliac artery (IIA) usually require exclusion of the IIA, exposing pelvic
      ischemic complication risks. This case report presents an endovascular technique
      of "cross-stenting" in a short proximal landing zone with complete exclusion of
      the CIA aneurysm using a covered stent graft with a longer uncovered stent
      extending into one branch of the IIAs, maintaining full pelvic circulation.
      External iliac artery to IIA cross-stenting with an additional uncovered stent
      warrants further investigation, because it seems to extend graft stent placement
      indications, increase stability, and help avoid IIA exclusion.

PMID- 20801683
TI  - Success of image-guided biopsy for small (<= 3 cm) focal liver lesions in
      cirrhotic and noncirrhotic individuals.
AB  - PURPOSE: Imaging techniques can detect small liver lesions, although these are a
      challenge to biopsy, particularly in cirrhotic liver. The authors assessed the
      diagnostic success of image-guided biopsies collected from small (<= 3 cm) focal
      liver lesions. MATERIALS AND METHODS: This single-center, retrospective study
      included 374 patients (199 men; mean age, 62 +/- 15). Eighteen-gauge core biopsy
      and 22-gauge fine needle aspiration (FNA) samples were collected from small focal
      liver lesions. Samples were compared by histology versus cytology, malignant
      versus benign, from lesions smaller versus larger than 1.5 cm, from livers with
      versus without cirrhosis, collected by computed tomography (CT) guidance versus
      ultrasound, and from different locations in the liver. RESULTS: The combined
      accuracy of core biopsy plus FNA analysis was 95.5%; core biopsy alone
      characterized 93.3% of samples, and FNA alone characterized 72.5% (P < .001).
      Biopsy successfully characterized 94.5% of malignant lesions and 98.8% of benign
      lesions (P > .05). Biopsy characterized 95.3% (102 of 107) lesions <= 1.5 cm. The
      success in cirrhotic livers was 94.8%, for CT-guided biopsies was 95%, and for
      ultrasound-guided biopsies was 95.8% (P > .05). The success rate was lower in
      liver caudate lobe than in other locations (P < .05). CONCLUSIONS: Image-guided
      biopsy of small (<= 3 cm) focal liver lesions is highly reliable with the use of
      core biopsy alone. Neither size <= 1.5 cm nor presence of cirrhosis is an
      impediment to biopsy. CT and ultrasound guidance produce similar rates of
      success.

PMID- 20801684
TI  - Radiofrequency ablation of a spinal osteoid osteoma: low heat-load technique.
AB  - The present report describes successful radiofrequency ablation of a small
      osteoid osteoma in the second lumbar (L2) pedicle of a 10-year-old boy who had
      been experiencing several months of back pain. The lesion had no cortical bone
      separation from the spinal canal contents and was positioned immediately adjacent
      to a synovial facet joint. Treatment involved a low heat-load technique to avoid
      damage to nearby sensitive structures. The adjacent epidural space was monitored
      for temperature increase.

PMID- 20801685
TI  - Percutaneous occlusion of the left subclavian and celiac arteries before or
      during endograft repair of thoracic and thoracoabdominal aortic aneurysms with
      detachable nitinol vascular plugs.
AB  - PURPOSE: To review an experience with the Amplatzer vascular plug (AVP) for
      prevention of type II endoleaks during endovascular aneurysm repair (EVAR) of
      thoracic and thoracoabdominal aneurysms. MATERIALS AND METHODS: Retrospective
      review was undertaken of 14 patients undergoing transcatheter occlusion of the
      left subclavian (n = 12) or celiac artery (n = 2) with the AVP as part of EVAR of
      thoracic and thoracoabdominal aneurysms at a single institution. Procedural
      criteria evaluated were success at target vessel occlusion, the number of AVPs
      used, use of adjunctive embolization devices, and embolization-related ischemic
      end-organ events. Follow-up imaging criteria included evaluation of persistent
      target vessel occlusion, evidence of device migration, and the presence and
      characterization of endoleak secondary to AVP failure. RESULTS: Complete target
      vessel occlusion was documented for all cases. In six cases, more than one AVP
      was placed, with an average of 1.5 devices per patient. In two cases, adjunctive
      coils were placed. Computed tomographic or magnetic resonance angiography follow
      up was available for all patients (mean follow-up, 419 days; range 28-930 d). No
      case showed evidence of device migration or type II endoleak resulting from AVP
      failure. There was a single instance of left subclavian artery recanalization
      without type II endoleak. There were no embolization-related ischemic end-organ
      events. CONCLUSIONS: Transcatheter arterial occlusion of the subclavian and
      celiac arteries with the AVP is a valuable adjunct to endografting in cases in
      which side branch embolization is necessary to extend the landing zone.

PMID- 20801686
TI  - Stent-grafts for transjugular intrahepatic portosystemic shunt creation:
      specialized TIPS stent-graft versus generic stent-graft/bare stent combination.
AB  - PURPOSE: To compare functional and anatomic outcomes of transjugular intrahepatic
      portosystemic shunts (TIPSs) created with the specialized Viatorr stent versus a
      Wallstent/Fluency stent combination. MATERIALS AND METHODS: Retrospective review
      of patients who underwent TIPS creation with stent-grafts was conducted over a 54
      month period ending in June 2008. Patients were divided into three groups:
      Viatorr only, Fluency only, and combined Viatorr/Fluency, the latter of which was
      included in the overall evaluation but excluded from the comparative analysis
      between the Viatorr and Fluency groups. Patient demographics, Child-Pugh scores,
      and portosystemic gradient (PSG) reduction were compared. Patencies were
      calculated using the Kaplan-Meier method and compared. RESULTS: A total of 126
      TIPSs created with stent-grafts were found: 28 with Fluency stents, 93 with
      Viatorr devices, and five combined. No significance in demographic factors or
      PSGs was found among groups (P > .05). Major encephalopathy rates were 3.6% and
      4.3% in the Fluency and Viatorr groups, respectively (P = 1.000). Hemodynamic
      success rates were 93% and 98% in the Fluency and Viatorr groups, respectively (P
      = .099). The primary unassisted patency rates at 6, 9, and 12 months were 87%,
      81%, and 81%, respectively, in the Fluency group and 95%, 93%, and 89%,
      respectively, in the Viatorr group (P = .03). Portal and hepatic end stenoses
      were the causes of TIPS narrowing in the Fluency and Viatorr groups,
      respectively. CONCLUSIONS: The Wallstent/Fluency stent combination is associated
      with a 1-year patency rate greater than 80%, with no significant difference
      versus the Viatorr stent regarding technical and hemodynamic success and
      encephalopathy rate. However, the Viatorr stent is associated with improved
      patency (89%) versus this bare stent/stent-graft combination.

PMID- 20801687
TI  - The cannon catheter--a prospective analysis.
AB  - Clinical outcomes associated with hemodialysis catheters often depend on correct
      tip positioning. Improper positioning of the catheter tips can reduce blood flow
      and lead to long-term complications. The authors evaluated the clinical
      performance of the Arrow Cannon II Plus hemodialysis catheter (Teleflex Medical,
      Research Triangle Park, North Carolina), a catheter that was designed for tip
      first (retrograde) placement to ensure accurate central positioning in the right
      atrium for optimal flow and minimal recirculation. This 6-month prospective
      analysis found that the catheter provided high blood flow rates (maximum flow,
      410.9-to 430.4 mL/min; mean flow, 378.9-402.4 mL/min) with recirculation rates
      well below the Kidney Disease Outcomes Quality Initiative (KDOQI) limit (3.6% to
      0%). In summary, the Arrow Cannon II Plus hemodialysis catheter was associated
      with high blood flow rates and minimal complications. Tip-first placement of this
      novel device represents an important advancement in vascular access for high
      performance hemodialysis.

PMID- 20801688
TI  - Transcatheter arterial chemoembolization for liver metastases in patients with
      adrenocortical carcinoma.
AB  - PURPOSE: To retrospectively evaluate the effectiveness, tolerance, and predictors
      of response to transcatheter arterial chemoembolization for treatment of liver
      metastases from adrenocortical carcinoma. MATERIALS AND METHODS: Twenty-nine
      patients with progressive liver metastases from adrenocortical carcinoma were
      treated with transcatheter arterial chemoembolization. Rate and duration of tumor
      response were defined according to Response Evaluation Criteria In Solid Tumors.
      The size of liver metastases, percentage of liver involvement, and Lipiodol
      uptake were studied as potential predictive factors of response. Time to liver
      and metastatic lesion progression were considered as endpoints. RESULTS: Three
      months after transcatheter arterial chemoembolization, a liver morphologic
      response was observed in six of 29 patients (21%), stabilization in 18 (62%), and
      progression in five (17%). According to per-lesion analysis (n = 103), a
      morphologic response was observed in 23 lesions (22%), stabilization in 67 (65%),
      and progression in 13 (13%). Higher response rates were observed in cases in
      which the diameter of the target metastasis was 3 cm or smaller (P = .002) and in
      cases of high Lipiodol uptake (> 50%; P < .0001). On per-patient and per-lesion
      bases, progression rates were 32% and 55% at 6 months and 23% and 38% at 12
      months. The median time to progression was 9 months and median survival was 11
      months after the first procedure. CONCLUSIONS: Transcatheter arterial
      chemoembolization should be considered as part of the therapeutic arsenal to
      treat liver metastases from adrenocortical carcinoma. The size of liver
      metastases and the percentage of Lipiodol uptake may help identify patients
      likely to benefit most from transcatheter arterial chemoembolization.

PMID- 20801690
TI  - Technical guide: transfibular ankle arthrodesis with fibular-onlay strut graft.
AB  - A wide range of techniques have been described for ankle arthrodesis, and
      although all of these have been shown to provide stability, few have been shown
      to achieve a solid construct in patients at risk of nonunion. In this technical
      guide, we describe a modified transfibular approach to ankle arthrodesis that
      uses a fibular-onlay strut graft for use in patients at high risk for nonunion.
      In our experience, the technique has been effective and reliable.

PMID- 20801689
TI  - Sudden death due to myocardial metastasis of lingual squamous cell carcinoma.
AB  - Cardiac metastases are rare events encountered in pathological practice but with
      often dramatic fatal outcome. Among malignancies associated with cardiac
      involvement, we would like to draw the attention of clinicians about lingual
      squamous cell carcinoma by reporting a sudden cardiac death in a 57-year-old
      woman without prior symptom and considered in remission 1 month before her death.
      The forensic autopsy led to the diagnosis emphasizing its role in epidemiology
      and public health.

PMID- 20801691
TI  - The use of negative pressure wound therapy for random local flaps at the ankle
      region.
AB  - Local random flaps are seldom used for reconstruction of complex ankle wounds
      because of concern for flap failure attributable to vascular compromise and
      tissue edema. Negative pressure wound therapy has been shown to improve perfusion
      and limit tissue edema. The objective of this study was to demonstrate the
      utility of negative pressure wound therapy in improving outcomes for local flaps
      of the ankle. Ten consecutive patients presenting with complex ankle wounds and
      reconstructed using local flaps were treated with negative pressure wound therapy
      postoperatively. Type of flap, immediate and long-term outcomes, and
      complications were assessed. Seventeen local flaps were performed on 10 patients
      to reconstruct their ankle wounds. Mean follow up was 88 days. All flaps healed
      without tissue compromise or necrosis. Only one partial dehiscence and no
      infections were observed. This study demonstrates that negative pressure therapy
      may contribute to the viability of random local flaps by decreasing venous
      congestion. Our experience using negative pressure wound therapy on local flaps
      suggests that it may serve as a useful adjunct to ensure successful closure of
      high-risk wounds.

PMID- 20801692
TI  - Is there a role for endoscopic therapy as a definitive treatment for post
      laparoscopic bile duct injuries?
AB  - BACKGROUND: Excellent results of surgical reconstruction of major bile duct
      injuries (BDIs) have been well-documented. Reports of successful definitive
      management of central bile duct leakage and stenoses have been reported
      infrequently. The aim of this study was to assess treatment and outcomes for
      operative and endoscopic treatment of BDI after laparoscopic cholecystectomy (LC)
      and define the role of endoscopy in management. STUDY DESIGN: All patients
      undergoing treatment for post-laparoscopic BDI from 1998 to 2007 at Mayo Clinic,
      Rochester, Minnesota were reviewed. Outcomes of surgical and endoscopic
      intervention were analyzed. RESULTS: BDI was identified in 159 patients (mean age
      51 years). Injury was recognized intraoperatively in 39 (25%) patients. Primary
      intervention was surgical in 59 (37%) and endoscopic in 100 (63%) patients. Class
      A BDIs (n = 77) were successfully treated endoscopically in 76 (99%) patients.
      Seven had class D BDIs; 4 were managed surgically, and 3 endoscopically. Of 66
      patients with E1 to E4 BDI, 44 (67%) were initially managed surgically and 22
      (33%) endoscopically. Thirteen of the latter 22 underwent sustained endoscopic
      therapy (median stent time 7 months), which was successful in 10 (77%). Four
      patients with E5 were managed surgically. Median follow-up was 45 months. Sixty
      three patients underwent Roux-en-Y hepaticojejunostomy reconstruction at Mayo; 3
      (5%) failed and required stenting. None required operative revision. CONCLUSIONS:
      Endoscopic management of class A BDI has excellent outcomes. Although surgical
      management remains the preferred therapy, short-term endoscopic treatment for
      class E1 to E4 can optimize the patient and operative field for reconstruction.
      Prolonged stenting in select patients with E1 to E4 characterized by stenosis is
      successful in the majority.

PMID- 20801693
TI  - Pancreatic anastomotic failure rate after pancreaticoduodenectomy decreases with
      microsurgery.
AB  - BACKGROUND: We have observed that leakage from pancreaticojejunostomy is reduced
      when a surgical microscope is used to construct the pancreaticojejunostomy during
      pancreaticoduodenectomy. To validate our hypothesis that better vision improves
      the technical performance of pancreaticojejunostomy, we limited inclusion
      criteria to those patients at high risk for leak, performed more cases, and used
      the grading system of the International Study Group of Pancreatic Surgery. STUDY
      DESIGN: From 1988 through 2008, 507 consecutive pancreaticoduodenectomies were
      performed with pancreaticojejunostomy. A subset of 283 patients at risk for leak
      had a main pancreatic duct (MPD) <=3 mm at the surgical margin.
      Pancreaticojejunostomy was completed with surgical loupes (n = 135) or surgical
      microscope (n = 148). Incidence of pancreaticojejunostomy leak and delayed
      gastric emptying was determined using a Web-based calculator for the severity
      grading scale of the International Study Group of Pancreatic Surgery. RESULTS:
      Within the 507 pancreaticoduodenectomies, the clinically relevant
      pancreaticojejunostomy leak for those with an MPD >3 mm (n = 224) was 4%, and
      with an MPD <=3 mm (n = 283) it was 16% (p < 0.0001). For these 283 high-risk
      patients, outcomes were worse in the loupes versus microscope group, ie,
      clinically relevant pancreaticojejunostomy leak (21% versus 11%; p = 0.021),
      pancreas-related complications (31% versus 19%; p = 0.018), clinically relevant
      delayed gastric emptying (19% versus 9%; p = 0.016), and hospital length of stay
      (12.9 versus 9.5 days; p < 0.0001). CONCLUSIONS: In a subset of
      pancreaticoduodenectomy patients at high risk for pancreaticojejunostomy leak,
      the increased visual acuity of the surgical microscope reduced clinically
      relevant pancreatic anastomotic failure, delayed gastric emptying, and hospital
      length of stay.

PMID- 20801694
TI  - Laparoscopic-assisted percutaneous gastrostomy tube placement in the initial
      management of resectable esophageal and gastroesophageal junction carcinoma.

PMID- 20801695
TI  - Resident participation does not affect surgical outcomes, despite introduction of
      new techniques.
AB  - BACKGROUND: Surgical operations at academic medical centers typically involve a
      resident physician performing cases together with, and/or under the supervision
      of, an attending physician. Although this is a widely accepted practice, recent
      emphasis on patient safety has led to scrutiny about this educational model.
      There are few studies evaluating whether complication rates, independent of
      patient risk factors, are affected by resident participation in operations. STUDY
      DESIGN: We identified 295 patients (590 breasts) who had undergone bilateral
      reduction mammoplasty led by a single attending surgeon between October 1, 1997
      and September 30, 2008 at the University of Michigan Health System. In all cases,
      the attending operated on the right breast and the resident operated on the left
      breast under the supervision of the attending, allowing each patient to act as
      their own control. Their charts were retrospectively reviewed and major
      complications were defined as those requiring either an operation or
      hospitalization to treat. RESULTS: Twenty-three patients (7.8%) had a major
      complication after their breast reduction. Ten of these complications occurred in
      the left breast, 9 in the right breast, and 4 in both breasts. Statistical
      analysis revealed no differences in major complication rates between the side
      operated on with the primary surgeon being the resident versus the attending
      (4.7% versus 4.4%; p = 1.00). CONCLUSIONS: In the context of this single surgical
      operation, resident participation does not substantially affect major
      complication rates. The common residency training paradigm provides clinical
      experience and supervision without necessarily impacting patient safety. Analysis
      of additional operations in different settings will be necessary.

PMID- 20801696
TI  - Fully automatic registration and segmentation of first-pass myocardial perfusion
      MR image sequences.
AB  - RATIONALE AND OBJECTIVES: Derivation of diagnostically relevant parameters from
      first-pass myocardial perfusion magnetic resonance images involves the tedious
      and time-consuming manual segmentation of the myocardium in a large number of
      images. To reduce the manual interaction and expedite the perfusion analysis, we
      propose an automatic registration and segmentation method for the derivation of
      perfusion linked parameters. MATERIALS AND METHODS: A complete automation was
      accomplished by first registering misaligned images using a method based on
      independent component analysis, and then using the registered data to
      automatically segment the myocardium with active appearance models. We used 18
      perfusion studies (100 images per study) for validation in which the
      automatically obtained (AO) contours were compared with expert drawn contours on
      the basis of point-to-curve error, Dice index, and relative perfusion upslope in
      the myocardium. RESULTS: Visual inspection revealed successful segmentation in 15
      out of 18 studies. Comparison of the AO contours with expert drawn contours
      yielded 2.23 +/- 0.53 mm and 0.91 +/- 0.02 as point-to-curve error and Dice
      index, respectively. The average difference between manually and automatically
      obtained relative upslope parameters was found to be statistically insignificant
      (P = .37). Moreover, the analysis time per slice was reduced from 20 minutes
      (manual) to 1.5 minutes (automatic). CONCLUSION: We proposed an automatic method
      that significantly reduced the time required for analysis of first-pass cardiac
      magnetic resonance perfusion images. The robustness and accuracy of the proposed
      method were demonstrated by the high spatial correspondence and statistically
      insignificant difference in perfusion parameters, when AO contours were compared
      with expert drawn contours.

PMID- 20801697
TI  - High-pitch 128-slice dual-source CT for the assessment of coronary stents in a
      phantom model.
AB  - RATIONALE AND OBJECTIVES: To evaluate the quality of stent lumen delineation
      using dual-source computed tomography (DSCT) in the standard-pitch mode (SP) as
      compared to the high-pitch mode (HP) in a phantom study. MATERIALS AND METHODS:
      Forty different coronary stents placed in plastic tubes filled with contrast
      agent were imaged with a second generation DSCT system in a SP (pitch 0.23) and
      HP (pitch 3.4) mode in orientations of 0 degrees , 45 degrees , and 90 degrees 
      relative to the z-axis. Two observers independently measured the in-stent lumen
      and the attenuation values in the center of the stents. The artificial lumen
      narrowing (ALN) was calculated using the measured in-stent lumen and the nominal
      diameter of the plastic tube. RESULTS: Interobserver correlation was excellent
      for in-stent lumen (0.86) and attenuation measurements (0.91). There was no
      significant difference neither for ALN (SP: 54.7-62.8%; HP: 55.8-64.0%) nor
      attenuation (SP: 356-395 Hounsfield units [HU]; HP: 352-384 HU) between SP and HP
      mode. For both modes, the orientation of the stent relative to the z-axis
      significantly affected ALN and attenuation (each P < .001). CT volume dose index
      was significantly lower using HP mode as compared to SP mode (P < .001).
      CONCLUSION: The HP mode in DSCT provides visualization of the coronary in-stent
      lumen comparable to that measured in SP mode while reducing applied radiation
      dose in a stationary phantom model.

PMID- 20801698
TI  - Optimal systolic and diastolic image reconstruction windows for coronary 256
      slice CT angiography.
AB  - RATIONALE AND OBJECTIVES: The aims of this study were to determine the optimal
      image reconstruction intervals for the systolic and diastolic phases of coronary
      computed tomographic angiography on 256-slice computed tomography and to assess
      their associated motion artifacts. MATERIALS AND METHODS: One hundred twenty-six
      patients were recruited (mean heart rate [HR], 72.1 beats/min; heart rate
      variability, 1.3 beats/min). Twenty data sets were reconstructed in 5% steps
      through 0% to 95% of the R-R interval. Two reviewers discriminated optimal
      reconstruction intervals for 15 segments distributed in three coronary arteries
      on the basis of motion artifacts, which were graded from 1 (no motion artifacts)
      to 4 (severe motion artifacts preventing diagnosis). Patients were then
      stratified into four HR groups for motion score comparison according to the
      results of a correlation analysis of HR and motion scores. RESULTS: The optimal
      systolic and diastolic reconstruction intervals were 44.4 +/- 3.8% and 77.4 +/-
      3.7%, respectively. The mean motion scores for systolic, diastolic, and combined
      systolic and diastolic (S+D) reconstructions were 1.8 +/- 0.3, 1.8 +/- 0.5, and
      1.5 +/- 0.3, respectively. Combined S+D reconstruction improved diagnostic
      evaluability to 100% and showed fewer motion artifacts compared to single-phase
      reconstructions for all HR ranges (S+D vs systolic, P < .05 for HR < 85
      beats/min; S+D vs diastolic, P < .05 for HRs of 73-84 beats/min). For HRs of 60
      to 72 beats/min, motion artifacts were significantly lower for diastole (1.6 +/-
      0.3) than systole (1.8 +/- 0.4) (P < .001), and vice versa for HRs of 73 to 84
      beats/min (1.7 +/- 0.3 for systole vs 2.0 +/- 0.5 for diastole, P < .01).
      CONCLUSIONS: Optimal systolic and diastolic reconstruction intervals were
      determined for this 256-slice coronary computed tomographic angiographic study.
      Combined reconstruction showed fewer motion artifacts compared to single-phase
      reconstruction. In conclusion, 256-slice computed tomography has the potential to
      improve the diagnostic accuracy of coronary computed tomographic angiography.

PMID- 20801699
TI  - Dissociation of rewarding, anti-aversive and anti-nociceptive effects of
      different classes of anti-nociceptives in the rat.
AB  - It was previously shown that morphine more potently reduces the affective as
      compared to the sensory component of nociception, and this effect is independent
      of morphine's rewarding properties. Here we investigated whether this finding can
      be generalized to other classes of anti-nociceptive drugs. The effect of
      oxycodone (0-10 mg/kg, i.p.), tramadol (0-10 mg/kg, i.p.), ibuprofen (0-300
      mg/kg, i.p.) and pregabalin (0-31.6 mg/kg, i.p.) on negative affect and
      mechanical hypersensitivity accompanying carrageenan-induced (0.5% intraplantar)
      inflammatory nociception was assessed using conditioned place aversion (CPA) and
      Randall Selitto paw pressure test, respectively. The rewarding effect of these
      drugs was assessed using conditioned place preference (CPP). All four anti
      nociceptive drugs dose-dependently reduced carrageenan-induced CPA and mechanical
      hypersensitivity. Furthermore all drugs induced CPP, except for ibuprofen.
      Similar to morphine, oxycodone and tramadol showed a large dissociation of anti
      aversive versus anti-nociceptive potency, i.e. 10 times more potent against the
      affective versus the sensory component of nociception. Oxycodone and tramadol
      were 30 and 10 times more potent to produce CPP in animals under normal versus
      painful conditions. Ibuprofen and pregabalin also showed a dissociation of anti
      aversive and anti-nociceptive potency, but less pronounced (i.e. three times more
      potent against the affective component). However, pregabalin showed no
      dissociation between rewarding potency under normal versus painful conditions.
      Taken together, these data suggest that the dissociation of rewarding potency in
      animals under normal versus painful conditions is limited to drugs with an opioid
      mechanism of action, while the dissociation of anti-aversive and anti-nociceptive
      potency applies to anti-nociceptive drugs with different mechanisms of action.

PMID- 20801700
TI  - Gaucher disease and parkinsonism, a molecular link theory.
AB  - Mutant GBA was found recently to be the most prevalent risk factor for familial
      parkinsonism. The two diseases do not share common symptoms and there is no
      direct pathway to explain the mechanism by which GBA mutations can confer the
      risk. Increased burden on the degradative pathway caused by defective
      glucocerebrosidase, or toxic side effects of glycosylated lipids accumulation
      were proposed to explain brain damage. Both hypotheses are not sufficient to
      explain the linkage. In order to develop a more inclusive theory we introduced
      into the model the prion theory and the second hit. Other possibilities are also
      brought into consideration.

PMID- 20801701
TI  - [Salvage treatments for prostatic radiation failure].
AB  - Local recurrence after external radiotherapy or brachytherapy occurs in 30% of
      patients treated for prostate cancer. These recurrences can be localised to the
      prostate and controlled by salvage treatment. Salvage prostatectomy is the gold
      standard treatment, however, it is associated with a high morbidity rate.
      Minimally invasive treatments such as cryotherapy and high intensity focused
      ultrasound (HIFU) can be proposed to treat local recurrences. Indications,
      complications and oncological results of these salvage treatments are discussed
      in this article.

PMID- 20801702
TI  - [Hypoplasia adrenal congenita of anencephalic type: two cases with pituitary
      abnormalities and review of literature].
AB  - Hypoplasia adrenal congenita is an extremely uncommon disease of early onset.
      This condition can be lethal in the absence of treatment. Some forms are due to
      the congenital adrenal hypoplasia of anencephalic type whose origin is even
      unknown. Here, we present two cases of congenital adrenal hypoplasia of
      anencephalic type with pituitary abnormalities. The two male newborns died
      because adrenal insufficiency in the neonatal period. The adrenal glands were
      hypoplastic with a histological structure of anencephalic type Immunocytochemical
      study of the pituitary revealed an absence of the gonadotrophs. No mutation of
      DAX 1 and SF-1 was found.

PMID- 20801703
TI  - [Donor sperm insemination after failed intracytoplasmic sperm injection].
AB  - After ICSI intracouple failure, donor sperm insemination (AID) is routinely
      offered. The prognostic factors and the rate of pregnancy resulting from this
      procedure are poorly documented (2 papers found). This retrospective study, which
      was conducted as part of the Federation of CECOS, completes a previous study and
      shows that female age, ovarian response and sperm characteristics were prognostic
      factors in obtaining a pregnancy with AID.

PMID- 20801704
TI  - Validation of an acoustic cavitation dose with hydroxyl radical production
      generated by inertial cavitation in pulsed mode: application to in vitro drug
      release from liposomes.
AB  - The purpose of this study was to define and validate an inertial cavitation dose
      (CD) based on the detection of broadband noise, designed to monitor ultrasound
      mediated drug release from liposomes. The validation consists of using the
      terephthalate dosimeter to quantify by fluorescence measurements the extent of
      hydroxyl radical (()OH) production during inertial cavitation. Sonication of
      samples was performed using tone bursts (pulse repetition frequency (PRF): 10 Hz(
      1) kHz, duty cycle (dc): 5-25%, Isppa: 4100-12,200 W/cm(2)) generated by a 1 MHz
      focused transducer. Three sets of ultrasound parameters with different PRF and dc
      were selected to be more precisely compared. Results demonstrated an excellent
      correlation between *OH radical production and CD for each set of parameters, but
      significant differences in hydroxyl radical levels were observed among the sets
      of parameters. The results were compared with other studies, and the same
      tendency of variation with pulse duration was demonstrated. Results also showed
      that the CD was not distorted by peak intensity variations and was a much more
      reliable indicator than sonication time. Consequently, one validated parameter
      was selected to monitor drug release from two liposome formulations, and compare
      their ultrasound sensitivity.

PMID- 20801705
TI  - Fast and easy synthesis of core-shell nanocrystal (CdS/TiO2) at low temperature
      by micro-emulsion under ultrasound.
AB  - CdS nanoparticles were easily combined with TiO(2) through a reaction in micro
      emulsion by means of ultrasonic irradiation. The formation of a uniform layer of
      TiO(2) on the CdS led to an increase of the size of nanoparticles. This is due to
      the appearance of a core-shell structure between the two combined semiconductors
      with a strong interface between them. TiO(2) shell depths were in the range of
      1.4-2.3 nm. Nano-scale depths of TiO(2) layers on the CdS can be easily
      controlled by adjusting the concentration of TTIP (titanium tetra-isopropoxide).
      Important variables such as the preparation method, molar ratio of the reactants,
      and time of sonication were investigated. Ultrasonic irradiation can control the
      hydrolysis and condensation of TTIP and the formation of a gradient TiO(2) shell
      around the CdS core. The nanoparticles were characterized by X-ray diffraction
      (XRD), UV-visible spectroscopy, energy dispersed analysis of X-ray (EDAX), HRTEM,
      SEM, and surface area measurements (BET).

PMID- 20801706
TI  - Assessing mobility at home in people with early Parkinson's disease using an
      instrumented Timed Up and Go test.
AB  - Gait and mobility problems are prominent features of Parkinson's Disease (PD),
      and are difficult to observe clinically in early stages of PD. We previously
      reported that gait changes were measurable in early to mid-stage PD subjects,
      when we used inertial sensors during an instrumented Timed Up and Go test (iTUG).
      With the advent of wearable inertial sensors, home assessment of mobility has
      become possible. We tested six people with early PD and eight control subjects
      using the iTUG in the home and laboratory. Our objectives were to 1) investigate
      the feasibility of testing subjects at home, and 2) compare performance at home
      versus laboratory. We found that home iTUG testing is feasible and the patients
      with PD were more affected than the healthy control subjects when tested at home.

PMID- 20801707
TI  - Array-based sensing with nanoparticles: 'chemical noses' for sensing biomolecules
      and cell surfaces.
AB  - Nanoparticle-based arrays have been used to distinguish a wide range of
      biomolecular targets through pattern recognition. In this report, we highlight
      new 'chemical nose' methodologies that use nanoparticle systems to provide high
      sensitivity sensing of biomolecular targets, including fluorescent polymer/gold
      nanoparticle complexes that can discriminate between different bioanalytes
      including proteins, bacteria, and mammalian cells as well as dye-based micellar
      systems for the detection of clinically important metalloproteins and
      nonmetalloproteins.

PMID- 20801708
TI  - Phytochrome: structural basis for its functions.
AB  - Phytochrome mediates various physiological as well as developmental responses to
      light stimuli in plants. Phytochrome is a soluble chromoprotein consisting of the
      N-terminal photosensory and C-terminal dimerization moieties. Close homologues of
      plant phytochromes are widely found in prokaryotes. Recently, the crystal
      structures of the core photosensory module of bacterial phytochromes are
      resolved. Intriguingly, three sub-domains (PAS, GAF and PHY) in the module are
      connected by unusual structures named 'light-sensing knot' and 'tongue', which
      are in tight contact with the chromophore. These findings enable us to review
      previous data on the structure-function relationships in phytochrome.
      Consequently, functional importance of these peculiar structures is further
      highlighted. Thus, the three-dimensional structure provides a framework for
      understanding how phytochrome processes the light signals.

PMID- 20801709
TI  - Binuclear cobalt(II), nickel(II), copper(II) and palladium(II) complexes of a new
      Schiff-base as ligand: synthesis, structural characterization, and antibacterial
      activity.
AB  - A binucleating new Schiff-base ligand with a phenylene spacer, afforded by the
      condensation of glycyl-glycine and o-phthalaldehyde has been served as an
      octadentate N4O4 ligand in designing some binuclear complexes of cobalt(II),
      nickel(II), copper(II), and palladium(II). The binding manner of the ligand to
      the metal and the composition and geometry of the metal complexes were examined
      by elemental analysis, conductivity measurements, magnetic moments, IR, 1H, 13C
      NMR, ESR and electronic spectroscopies, and TGA measurements. There are two
      different coordination/chelation environments present around two metal centers of
      each binuclear complex. The composition of the complexes in the coordination
      sphere was found to be [M2(L)(H(2)O)4] (where M=Co(II) and Ni(II)) and [M2(L)]
      (where M=Cu(II) and Pd(II)). In the case of Cu(II) complexes, ESR spectra
      provided further information to confirm the binuclear structure and the presence
      of magnetic interactions. All the above metal complexes have shown moderate to
      good antibacterial activity against Gram-positive and Gram-negative bacteria.

PMID- 20801710
TI  - Molecular spectroscopic analysis of nano-chitosan blend as biosensor.
AB  - Chitosan/starch and chitosan/gelatin of different ratios were prepared following
      casting method. FTIR results indicate the formation of hydrogen bonding which
      dedicates the prepared blends for interaction with wide range of molecules
      specially those of NH2 and COOH terminals. The results obtained with molecular
      modeling PM3 model are in agreement with spectroscopic data. As a result of
      increasing starch and gelatin in chitosan blends HOMO-LUMO energy slightly
      decreased while total dipole moment increased. UV-vis spectroscopy indicated the
      suitability of chitosan/starch blend as a glycine sensor. Further enhancement in
      the sensing performance of chitosan/starch blend was achieved by introducing 5 nm
      TiO2 into the blend.

PMID- 20801711
TI  - A series of transition and non-transition metal complexes from a N4O2 hexadentate
      Schiff base ligand: Synthesis, spectroscopic characterization and efficient
      antimicrobial activities.
AB  - Some transition and non-transition metal complexes of the hexadentate N4O2 donor
      Schiff base ligand 1,8-N-bis(3-carboxy)disalicylidene-3,6-diazaoctane-1,8
      diamine, abbreviated to H4fsatrien, have been synthesized. All the 14 metal
      complexes have been fully characterized with the help of elemental analyses,
      molecular weights, molar conductance values, magnetic moments and spectroscopic
      (UV-Vis, IR, NMR, ESR) data. The analytical data helped to elucidate the
      structures of the metal complexes. The Schiff base, H4fsatrien, is found to act
      as a dibasic hexadentate ligand using N2N2O2 donor set of atoms (leaving the COOH
      group uncoordinated) leading to an octahedral geometry for the complexes around
      all the metal ions except VO2(+) and UO22(+). However, surprisingly the same
      ligand functions as a neutral hexadentate and neutral tetradentate one towards
      UO22(+) and VO2(+), respectively. In case of divalent metal complexes they have
      the general formula [M(H2fsatrien)] (where M stands for Cu, Co, Hg and Zn); for
      trivalent metal complexes it is [M(H2fsatrien)]X.nH2O (where M stands for Cr, Mn,
      Fe, Co and X stands for CH3COO, Cl, NO3, ClO4) and for the complexes of VO2(+)
      and UO22(+), [M(H4fsatrien)]Y (where M=VO and Y=SO4); M=UO2 and Y=2 NO3). The
      Schiff base ligand and most of the complexes have been screened in vitro to judge
      their antibacterial (Escherichia coli and Staphylococcus aureus) and antifungal
      (Aspergillus niger and Pencillium chrysogenum) activities.

PMID- 20801712
TI  - Spectroscopic investigation of the interaction between diperoxovanadate complexes
      and benzimidazole-like ligands.
AB  - To understand the effects of benzimidazole substitution on reaction equilibrium,
      the interactions between a series of benzimidazole-like ligands and
      [OV(O2)2(D2O)]-/[OV(O2)2(HOD)]- in solution were explored by a combination of
      multinuclear ((1)H, (13)C, and (51)V) magnetic resonance and variable temperature
      NMR in 0.15 mol/L NaCl ionic medium for mimicking the physiological condition.
      Some direct NMR data are reported for the first time. These results show that the
      relative reactivity among the organic ligands is 2-methyl-1H
      benzo[d]imidazole>(1H-benzo[d]imidazol-2-yl)methanol>1-(1H-benzo[d]imidazol-2
      yl)ethanol>1H-benzo[d][1,2,3]triazole. Both the steric effect and the electron
      effect of the 2-position substituted groups in benzimidazole ring affect the
      reaction equilibrium. The competitive coordination results in the formation of a
      series of new six-coordinated peroxovanadate species [OV(O2)2L]-(L=benzimidazole
      like ligands). Moreover, the results of density functional calculations provided
      a reasonable explanation on the relative reactivity of the benzimidazole-like
      ligands as well as the important role of solvation in these reactions.

PMID- 20801713
TI  - Modulated differentiation of embryonic stem cells into hepatocyte-like cells by
      coculture with hepatic stellate cells.
AB  - We investigated the effects of coculture with hepatic stellate cells (HSCs) on
      the differentiation of embryonic stem (ES) cells and embryoid bodies (EBs). Rat
      HSCs were incubated until becoming semi-confluent and adherent to the dish.
      Undifferentiated mouse ES cells and 4-day EBs were cultured in gelatin-coated or
      HSC-feeder dishes, then induced hepatocyte-like cells and the remaining
      undifferentiated ES cells were examined using immunocytochemical and RT-PCR
      methods. HSCs promoted the differentiation of EBs into hepatocyte-like cells,
      whereas they inhibited the differentiation of undifferentiated ES cells. Among EB
      outgrowths cocultured with HSCs, albumin-immunopositive cells were clearly and
      abundantly observed, while they were faintly and scarcely seen in EB outgrowths
      without HSCs. mRNA expressions of the hepatocyte-related markers such as albumin,
      transthyretin, alpha-1-antitrypsin, tryptophan-2,3-dioxygenase,
      phosphoenolpyruvate carboxykinase, hepatocyte nuclear factor 4alpha and
      cytochrome P4507a1 were clearly detected in EB outgrowths cocultured with HSCs,
      while they were only weakly detected or undetected in spontaneous EB outgrowths
      without HSCs. In contrast to the promoted hepatic differentiation of EBs by HSCs,
      undifferentiated ES cells formed cellular colonies in HSC-feeder dishes that were
      similar to the colonies of undifferentiated ES cells kept in maintenance medium
      containing leukemia inhibitory factor. In addition, ES cell colonies were
      immunopositive for Oct-3/4, markers of an undifferentiated state, and there were
      few ALB-immunopositive cells in the colonies. Thus, HSCs have contrasting effects
      on EBs undergoing differentiation and undifferentiated ES cells, i.e., positive
      and negative modulation, respectively.

PMID- 20801714
TI  - Extraction and in vitro antioxidant activity of intracellular polysaccharide by
      Pholiota adiposa SX-02.
AB  - Response surface methodology (RSM) was used to optimize the extraction parameters
      for Pholiota adiposa SX-02 intracellular polysaccharide (IPS) produced during
      submerged culture. The optimum conditions of IPS extraction were predicted to be,
      ultrasonic power at 564.93 W, precipitation time 30.34 h and pH 8.28, and IPS
      yield was estimated at 19.75%. The actual value of IPS under these conditions was
      20.51%. The in vitro antioxidant results showed that the inhibition effects of
      IPS at a dosage of 250 mg/l on superoxide anion, hydroxyl and 1,1-diphenyl-2
      picrylhydrazyl (DPPH) radical were 74.66 +/- 5.31%, 69.20 +/- 5.13%, and 75.20 +/
      6.73%, respectively, which were 27.51 +/- 2.23%, 16.58 +/- 1.33%, and 9.46 +/-
      0.72% higher than that of butylated hydroxytoluene (BHT), respectively. The
      reducing power of IPS was 0.32 +/- 0.02 (absorbance at 700 nm), 39.13 +/- 3.47%
      higher than that of BHT. The results provide a reference for large-scale
      extraction of IPS by P. adiposa SX-02 in industrial fermentation and the IPS can
      be used as a potential antioxidant which enhances adaptive immune responses.

PMID- 20801715
TI  - Development of the Pediatric Restless Legs Syndrome Severity Scale (P-RLS-SS): a
      patient-reported outcome measure of pediatric RLS symptoms and impact.
AB  - OBJECTIVE: To develop a questionnaire to measure Pediatric Restless Legs Syndrome
      (P-RLS) symptoms and impact for use in clinical research. METHODS: Questionnaire
      items were developed based on open-ended, qualitative interviews of 33 children
      and adolescents diagnosed with definite RLS (ages 6-17 years) and their parents.
      The draft questionnaire was then tested through cognitive debriefing interviews
      with 21 of the same children/adolescents and 15 of their parents. This involved
      the children and parents answering the draft items and then interviewing them
      about the child's ability to understand and interpret the questionnaire. Expert
      clinicians provided clinical guidance throughout. RESULTS: Draft severity
      questions were generated to measure the four-symptom and four-impact domains
      identified from the concept elicitation interviews: RLS sensations, move/rub due
      to RLS, relief from move/rub, pain, and impact of RLS on sleep, awake activities,
      emotions, and tiredness. RLS descriptions, symptoms, and impact were compared
      between those who had comorbid attention-deficit/hyperactivity disorder and those
      who did not. Revisions to several questions were made based on the cognitive
      debriefing interviews and expert clinician review, resulting in a severity scale
      with 17 morning and 24 evening items. Caution regarding self-administration in
      children ages 6-8 years is recommended. To complement the child/adolescent
      measures, a separate parent questionnaire was also developed. CONCLUSIONS: The P
      RLS-SS was constructed based on detailed input from children and adolescents with
      RLS, their parents, and clinical experts, thus providing a scale with strong
      content validity that is intended to be comprehensive, clinically relevant, and
      important to patients. Validation of this scale is recommended.

PMID- 20801716
TI  - Evolution of dyskinetoplastic trypanosomes: how, and how often?

PMID- 20801717
TI  - Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven
      other countries: a genome-wide association study.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of
      motor neurons that results in progressive weakness and death from respiratory
      failure, commonly within about 3 years. Previous studies have shown association
      of a locus on chromosome 9p with ALS and linkage with ALS-frontotemporal
      dementia. We aimed to test whether this genomic region is also associated with
      ALS in an independent set of UK samples, and to identify risk factors associated
      with ALS in a further genome-wide association study that combined data from the
      independent analysis with those from other countries. METHODS: We collected
      samples from patients with sporadic ALS from 20 UK hospitals and obtained UK
      control samples from the control groups of the Depression Case Control study, the
      Bipolar Affective Case Control Study, and the British 1958 birth cohort DNA
      collection. Genotyping of DNA in this independent analysis was done with Illumina
      HumanHap550 BeadChips. We then undertook a joint genome-wide analysis that
      combined data from the independent set with published data from the UK, USA,
      Netherlands, Ireland, Italy, France, Sweden, and Belgium. The threshold for
      significance was p=0.05 in the independent analysis, because we were interested
      in replicating a small number of previously reported associations, whereas the
      Bonferroni-corrected threshold for significance in the joint analysis was
      p=2.20*10(-7) FINDINGS: After quality control, samples were available from 599
      patients and 4144 control individuals in the independent set. In this analysis,
      two single nucleotide polymorphisms in a locus on chromosome 9p21.2 were
      associated with ALS: rs3849942 (p=2.22*10(-6); odds ratio [OR] 1.39, 95% CI 1.21
      1.59) and rs2814707 (p=3.32*10(-6); 1.38, 1.20-1.58). In the joint analysis,
      which included samples from 4312 patients with ALS and 8425 control individuals,
      rs3849942 (p=4.64*10(-10); OR 1.22, 95% CI 1.15-1.30) and rs2814707 (p=4.72*10(
      10); 1.22, 1.15-1.30) were associated with ALS. INTERPRETATION: We have found
      strong evidence of a genetic association of two single nucleotide polymorphisms
      on chromosome 9 with sporadic ALS, in line with findings from previous
      independent GWAS of ALS and linkage studies of ALS-frontotemporal dementia. Our
      findings together with these earlier findings suggest that genetic variation at
      this locus on chromosome 9 causes sporadic ALS and familial ALS-frontotemporal
      dementia. Resequencing studies and then functional analysis should be done to
      identify the defective gene.

PMID- 20801719
TI  - Chromosome 9p21 in amyotrophic lateral sclerosis: the plot thickens.

PMID- 20801718
TI  - Chromosome 9p21 in amyotrophic lateral sclerosis in Finland: a genome-wide
      association study.
AB  - BACKGROUND: The genetic cause of amyotrophic lateral sclerosis (ALS) is not well
      understood. Finland is a well suited location for a genome-wide association study
      of ALS because the incidence of the disease is one of the highest in the world,
      and because the genetic homogeneity of the Finnish population enhances the
      ability to detect risk loci. We aimed to identify genetic risk factors for ALS in
      the Finnish population. METHODS: We did a genome-wide association study of
      Finnish patients with ALS and control individuals by use of Illumina genome-wide
      genotyping arrays. DNA was collected from patients who attended an ALS specialty
      clinic that receives referrals from neurologists throughout Finland. Control
      samples were from a population-based study of elderly Finnish individuals.
      Patients known to carry D90A alleles of the SOD1 gene (n=40) were included in the
      final analysis as positive controls to assess whether our genome-wide association
      study was able to detect an association signal at this locus. FINDINGS: We
      obtained samples from 442 patients with ALS and 521 control individuals. After
      quality control filters were applied, 318 167 single nucleotide polymorphisms
      (SNPs) from 405 people with ALS and 497 control individuals were available for
      analysis. We identified two association peaks that exceeded genome-wide
      significance. One was located on chromosome 21q22 (rs13048019, p=2.58*10(-8)),
      which corresponds to the autosomal recessive D90A allele of the SOD1 gene. The
      other was detected in a 232 kb block of linkage disequilibrium (rs3849942,
      p=9.11*10(-11)) in a region of chromosome 9p that was previously identified in
      linkage studies of families with ALS. Within this region, we defined a 42-SNP
      haplotype that was associated with significantly increased risk of ALS
      (p=7.47*10(-33) when people with familial ALS were compared with controls, odds
      ratio 21.0, 95% CI 11.2-39.1) and which overlapped with an association locus
      recently reported for frontotemporal dementia. For the 93 patients with familial
      ALS, the population attributable risk for the chromosome 9p21 locus was 37.9%
      (95% CI 27.7-48.1) and that for D90A homozygosity was 25.5% (16.9-34.1).
      INTERPRETATION: The chromosome 9p21 locus is a major cause of familial ALS in the
      Finnish population. Our data suggest the presence of a founder mutation for
      chromosome 9p21-linked ALS. Furthermore, the overlap with the risk haplotype
      recently reported for frontotemporal dementia provides further evidence of a
      shared genetic cause for these two neurodegenerative diseases. FUNDING: National
      Institutes of Health and National Institute on Aging, Microsoft Research, ALS
      Association, Helsinki University Central Hospital, Finnish Academy, Finnish
      Medical Society Duodecim, and Kuopio University.

PMID- 20801720
TI  - Early insertion of trans-scrotal port during laparoscopic orchidopexy: a new
      concept.
AB  - Laparoscopic orchidopexy has become the routine tool in managing abdominal
      testes. Many techniques have been used to deliver the dissected testis to the
      scrotal position; a trans-scrotal port is one of them. We present a technique in
      which the trans-scrotal port is inserted early on, and used not only for testis
      delivery but also to aid the testicular dissection. We used the technique for 15
      abdominal testes in 13 boys and it was safe, and very helpful in dissecting the
      vascular pedicle to higher levels in an ergonomically easier plane. In addition,
      it helped in establishing the tract and eventually guiding the dissected testis
      to the desired scrotal position (12 low and 3 mid-scrotal).

PMID- 20801721
TI  - Refractory nonconvulsive status epilepticus responsive to music as an add-on
      therapy: a second case.

PMID- 20801722
TI  - The effect of surgery on the postictal state.
AB  - The effect of surgery on the postictal state has not been studied in a systematic
      fashion. There is limited literature looking at the effect on postictal
      psychosis. The effect of surgery on this phenomenon has been varied with post
      ictal psychosis occurring post surgery when it has not occurred prior to surgery
      as well as resolution after surgery. Case reports of post ictal Kluver Bucy
      Syndrome and Capgas Syndrome have been reported after resective epilepsy surgery
      as well.

PMID- 20801724
TI  - Pregabalin-induced severe delayed ejaculation.

PMID- 20801723
TI  - Vascular endothelial growth factor attenuates status epilepticus-induced
      behavioral impairments in rats.
AB  - Vascular endothelial growth factor (VEGF) is a vascular growth factor more
      recently recognized as a neurotrophic factor (for review, see Storkebaum E,
      Lambrechts D, Carmeliet P. BioEssays 2004;26:943-54). We previously reported that
      endogenous VEGF protein is dramatically upregulated after pilocarpine-induced
      status epilepticus in the rat, and that intra-hippocampal infusions of
      recombinant human VEGF significantly protected against the loss of hippocampal
      CA1 neurons in this model (Nicoletti JN, Shah SK, McCloskey DP, et al.
      Neuroscience 2008;151:232-41). We hypothesized that we would see a preservation
      of cognitive and emotional functioning with VEGF treatment accompanying the
      neuroprotection previously observed in this paradigm. Using the Morris water maze
      to evaluate learning and memory, and the light-dark task to assess anxiety, we
      found a selective profile of preservation. Specifically, VEGF completely
      preserved normal anxiety functioning and partially but significantly protected
      learning and memory after status epilepticus. To determine whether the ability of
      VEGF to attenuate behavioral deficits was accompanied by sustained preservation
      of hippocampal neurons, we stereologically estimated CA1 pyramidal neuron
      densities 4 weeks after status epilepticus. At this time point, we found no
      significant difference in neuronal densities between VEGF- and control-treated
      status epilepticus animals, suggesting that VEGF could have protected hippocampal
      functioning independent of its neuroprotective effect.

PMID- 20801725
TI  - Obesity under affluence varies by welfare regimes: the effect of fast food,
      insecurity, and inequality.
AB  - Among affluent countries, those with market-liberal welfare regimes (which are
      also English-speaking) tend to have the highest prevalence of obesity. The impact
      of cheap, accessible high-energy food is often invoked in explanation. An
      alternative approach is that overeating is a response to stress, and that
      competition, uncertainty, and inequality make market-liberal societies more
      stressful. This ecological regression meta-study pools 96 body-weight surveys
      from 11 countries c. 1994-2004. The fast-food 'shock' impact is found to work
      most strongly in market-liberal countries. Economic insecurity, measured in
      several different ways, was almost twice as powerful, while the impact of
      inequality was weak, and went in the opposite direction.

PMID- 20801726
TI  - [Management of thyroid cancer in Spain].

PMID- 20801727
TI  - Feeling body dissatisfied after viewing thin-ideal pictures is mediated by self
      activation.
AB  - The present study sought to investigate the influence of self-activation on body
      and weight satisfaction in restrained and unrestrained eaters, after exposure to
      thin-ideal images. Restrained eaters (n=39) and unrestrained eaters (n=40) were
      randomly assigned to a self-activation manipulation versus a control
      manipulation. After the manipulation, all participants were exposed to eight thin
      ideal images. Measures of state body and weight satisfaction and of social
      comparison tendencies were assessed throughout the experiment. Self-activated
      restrained eaters showed a significant decrease in body and weight satisfaction
      after exposure to thin-ideal images, compared to restrained eaters who were not
      self-activated. In unrestrained eaters, the self-activation manipulation did not
      have any effect on body or weight dissatisfaction. In conclusion, exposure to
      fashion models only had a negative influence on women's self-evaluations when two
      conditions were met: (1) the participant was 'self-activated' and (2) the
      participant classified as a restrained eater.

PMID- 20801728
TI  - Turning routine NHS data into health care intelligence: NHS clinicians need
      public health doctors in primary care trusts (PCTs).

PMID- 20801729
TI  - Y-STR haplotypes in three ethnic linguistic groups of Angola population.

PMID- 20801730
TI  - Fiber Bragg grating sensor for monitoring bone decalcification.
AB  - INTRODUCTION: Estimation of decalcification is a vital tool to discern bone
      health. Different techniques are used for its quantitative measurement, e.g.
      DEXA, QCT & QUS. All these techniques, although noninvasive, suffer from
      limitations such as radiation exposure and inaccurate values. Recently, fiber
      optic techniques are fast emerging for medical applications owing to their
      various attractive features like immunity to EMI/RFI, geometric versatility,
      chemical inertness, etc. MATERIAL AND METHODS: The effect of decalcification on
      strain response of a goat tibia was investigated in vitro using fiber Bragg
      grating (FBG) sensing technique. The bone was strained by using three-point
      bending technique and corresponding Bragg wavelength shifts were recorded. Two
      similar bone samples from the same animal were taken and one was partially
      decalcified. Strain response of decalcified and untreated bone was taken
      concurrently to monitor the effects of calcium loss and that of degradation with
      time. RESULTS AND CONCLUSION: The strain generated for same stress increased with
      greater degree of decalcification and a steep increase occurred after 2g calcium
      loss, indicating the onset of damage. The strain response, therefore gives a
      direct indication of the degree of calcium present in the bone. LEVEL OF
      EVIDENCE: Level III.

PMID- 20801731
TI  - Intermediate term functional outcome prediction following full thickness rotator
      cuff tear reparative or not reparative surgery.
AB  - Although simple suturing repair of a full thickness cuff tear can be performed
      when the preoperative fatty degeneration index (FDI) is 2 or less, it is not
      known if the functional results will be better than palliative surgical
      treatment. The aim of this study is to describe and validate a method to predict
      the intermediate term unweighted Constant scores of different surgical treatments
      based on preoperative FDI. The hypothesis of this study is that the preoperative
      and final follow-up ratios FDI/final follow-up Constant scores regression lines,
      established on a previous "reference study"[5] (a series of 29 shoulders with
      cuff tears and sutured intact rotator cuff), could be used for this purpose.
      MATERIAL: The present study included seven series of sutured cuffs (five, which
      resulted in intact cuffs and two in recurrent tears) and one series of cuffs
      treated with palliative surgery. Knowledge of the preoperative FDI and the
      location of the recurrent or unrepaired tears were required criteria for these
      series inclusion in the study. METHOD: For each of the series in this study the
      Constant scores and selected score items were compared to scores calculated with
      the same mathematical formulas previously used to determine the regression lines
      in the reference study series (resulting in Constant scores in relation to
      preoperative and final follow-up FDI). RESULTS: The calculated Constant scores
      were similar to those reported by the authors, which validate the proposed
      method. DISCUSSION: Because of the small size of the series of sutured cuffs with
      recurrent tears and of cuffs that underwent palliative surgery and arthroscopic
      treatment it is impossible to definitely confirm the validity of this method.
      CONCLUSION: The intermediate term results of different surgical treatments can
      reasonably be predicted for full thickness tendon tears based on the preoperative
      FDI and the location of these tears. With this method the best treatment should
      be chosen for a rotator cuff tear on a case-by-case basis. LEVEL OF EVIDENCE:
      Level IV.

PMID- 20801732
TI  - Proximal ulna comminuted fractures: fixation using a double-plating technique.
AB  - INTRODUCTION: Comminuted fractures of the proximal ulna are severe injuries often
      associated with bone and ligament injuries of the elbow joint (Monteggia lesion,
      radial head fractures, dislocation of the elbow). The treatment of these
      fractures is very demanding and the functional results often fairly mediocre due
      to associated injuries. Based on a single-center retrospective study, we report
      the results of the treatment of these fractures fixed using a double-plate
      technique. The aim was to evaluate the feasibility and reliability of this
      fixation mode and to compare it with other fractures series using a single plate
      fixation (in terms of bone union, elbow joint function, and complications
      stemming from the plates). PATIENTS AND METHODS: Eighteen patients sustained a
      comminuted proximal ulna fracture between 2002 and 2006. The fractures were
      associated in five cases with a Monteggia type lesion, in two cases with elbow
      dislocation, and in four cases with a Mason 3 radial head fracture. Four patients
      had an open fracture. These comminuted ulna fractures included nine Mayo Clinic
      IIIB fractures. Bone fixation was performed with two third-cylinder tubular
      plates, one plate on each side of the proximal ulna. This allows more versatile
      solutions for screw insertion. Functional assessment (according to Broberg and
      Morrey) and radiological evaluation (bone healing) were provided at 6 months and
      at the longest follow-up by an independent surgeon. RESULTS: Sixteen of 18
      patients achieved bone union. No septic complications occurred and no hardware
      removal was required on patient request. In 67% of the cases, the Morrey score
      indicated excellent or good results with a mean score of 82. DISCUSSION: There
      are no reports in the literature on the technical point of fixation concerning
      complex fractures of the ulna. Two plates mean the possibility of twice the
      number of screw insertions for epiphyseal reconstruction . This fixation remains
      easy to perform and provides stable anatomic reconstruction of the ulna. LEVEL OF
      EVIDENCE: Level IV. Retrospective study.

PMID- 20801733
TI  - Transanal endoscopic microsurgery.

PMID- 20801734
TI  - From histology to computed tomography: every picture tells a story.

PMID- 20801735
TI  - President's page: The way ahead.

PMID- 20801736
TI  - Comparison of parasitological and productive traits of Criollo lambs native to
      the central Mexican Plateau and Suffolk lambs experimentally infected with
      Haemonchus contortus.
AB  - The study compares the parasitological and productive traits of Criollo lambs
      native to the central Mexican Plateau (CNCMP) and Suffolk (SU) lambs
      experimentally infected with Haemonchus contortus. CNCMP lambs (n=20) and SU
      lambs (n=15) were infected with L3 of H. contortus while five lambs of each
      genotype were kept as controls. Fecal egg count (FEC), packed cell volume (PCV),
      blood eosinophil number (BEN), ocular mucous membrane color (as measured by the
      FAMACHA index), changes in body condition score (BCS) and cumulative live weight
      gain (CLWG) were measured weekly during a 20-week period. On week 20, all animals
      were euthanized and the number of adult worms (AW) in the abomasum was counted.
      Infected SU lambs had higher (p<0.05) FEC and AW mean values compared to CNCMP
      lambs, which had a higher mean BEN count (p<0.05). Infected lambs had lower PCV
      values than controls, regardless of genotype, and had a negative correlation (r=
      0.84, p<0.05) with the FAMACHA index. BCS tended to decline for infected SU lambs
      and increased slightly for infected CNCMP lambs. CLWG differed in all groups
      (p<0.05); infected SU lambs gained 12.1+/-1.9kg, infected CNCMP lambs gained
      18.8+/-0.7kg, control SU lambs gained 34.6+/-1.6kg, and control CNCMP lambs
      gained 26.9+/-0.8kg. In conclusion, CNCMP lambs had a smaller worm burden, a
      better ability to maintain their productive traits, and were less affected by
      infection with Haemonchus contortus.

PMID- 20801738
TI  - Interactive streaming of stored multiview video using redundant frame structures.
AB  - While much of multiview video coding focuses on the rate-distortion performance
      of compressing all frames of all views for storage or non-interactive video
      delivery over networks, we address the problem of designing a frame structure to
      enable interactive multiview streaming, where clients can interactively switch
      views during video playback. Thus, as a client is playing back successive frames
      (in time) for a given view, it can send a request to the server to switch to a
      different view while continuing uninterrupted temporal playback. Noting that
      standard tools for random access (i.e., I-frame insertion) can be bandwidth
      inefficient for this application, we propose a redundant representation of I-, P
      , and "merge" frames, where each original picture can be encoded into multiple
      versions, appropriately trading off expected transmission rate with storage, to
      facilitate view switching. We first present ad hoc frame structures with good
      performance when the view-switching probabilities are either very large or very
      small. We then present optimization algorithms that generate more general frame
      structures with better overall performance for the general case. We show in our
      experiments that we can generate redundant frame structures offering a range of
      tradeoff points between transmission and storage, e.g., outperforming simple I
      frame insertion structures by up to 45% in terms of bandwidth efficiency at twice
      the storage cost.

PMID- 20801739
TI  - Iterative shrinkage approach to restoration of optical imagery.
AB  - The problem of reconstruction of digital images from their degraded measurements
      is regarded as a problem of central importance in various fields of engineering
      and imaging sciences. In such cases, the degradation is typically caused by the
      resolution limitations of an imaging device in use and/or by the destructive
      influence of measurement noise. Specifically, when the noise obeys a Poisson
      probability law, standard approaches to the problem of image reconstruction are
      based upon using fixed-point algorithms which follow the methodology first
      proposed by Richardson and Lucy. The practice of using these methods, however,
      shows that their convergence properties tend to deteriorate at relatively high
      noise levels. Accordingly, in the present paper, a novel method for denoising
      and/or deblurring of digital images corrupted by Poisson noise is introduced. The
      proposed method is derived under the assumption that the image of interest can be
      sparsely represented in the domain of a linear transform. Consequently, a
      shrinkage-based iterative procedure is proposed, which guarantees the solution to
      converge to the global maximizer of an associated maximum a posteriori criterion.
      It is shown in a series of computer-simulated experiments that the proposed
      method outperforms a number of existing alternatives in terms of stability,
      precision, and computational efficiency.

PMID- 20801740
TI  - Missing intensity interpolation using a kernel PCA-based POCS algorithm and its
      applications.
AB  - A missing intensity interpolation method using a kernel principal component
      analysis (PCA)-based projection onto convex sets (POCS) algorithm and its
      applications are presented in this paper. In order to interpolate missing
      intensities within a target image, the proposed method reconstructs local
      textures containing the missing pixels by using the POCS algorithm. In this
      reconstruction process, a nonlinear eigenspace is constructed from each kind of
      texture, and the optimal subspace for the target local texture is introduced into
      the constraint of the POCS algorithm. In the proposed method, the optimal
      subspace can be selected by monitoring errors converged in the reconstruction
      process. This approach provides a solution to the problem in conventional methods
      of not being able to effectively perform adaptive reconstruction of the target
      textures due to missing intensities, and successful interpolation of the missing
      intensities by the proposed method can be realized. Furthermore, since our method
      can restore any images including arbitrary-shaped missing areas, its potential in
      two image reconstruction tasks, image enlargement and missing area restoration,
      is also shown in this paper.

PMID- 20801741
TI  - Enhanced shift and scale tolerance for rotation invariant polar matching with
      dual-tree wavelets.
AB  - Polar matching is a recently developed shift and rotation invariant object
      detection method that is based upon dual-tree complex wavelet transforms or
      equivalent multiscale directional filterbanks. It can be used to facilitate both
      keypoint matching, neighborhood search detection, or detection and tracking with
      particle filters. The theory is extended here to incorporate an allowance for
      local spatial and dilation perturbations. With experiments, we demonstrate that
      the robustness of the polar matching method is strengthened at modest
      computational cost.

PMID- 20801742
TI  - Distance regularized level set evolution and its application to image
      segmentation.
AB  - Level set methods have been widely used in image processing and computer vision.
      In conventional level set formulations, the level set function typically develops
      irregularities during its evolution, which may cause numerical errors and
      eventually destroy the stability of the evolution. Therefore, a numerical remedy,
      called reinitialization, is typically applied to periodically replace the
      degraded level set function with a signed distance function. However, the
      practice of reinitialization not only raises serious problems as when and how it
      should be performed, but also affects numerical accuracy in an undesirable way.
      This paper proposes a new variational level set formulation in which the
      regularity of the level set function is intrinsically maintained during the level
      set evolution. The level set evolution is derived as the gradient flow that
      minimizes an energy functional with a distance regularization term and an
      external energy that drives the motion of the zero level set toward desired
      locations. The distance regularization term is defined with a potential function
      such that the derived level set evolution has a unique forward-and-backward (FAB)
      diffusion effect, which is able to maintain a desired shape of the level set
      function, particularly a signed distance profile near the zero level set. This
      yields a new type of level set evolution called distance regularized level set
      evolution (DRLSE). The distance regularization effect eliminates the need for
      reinitialization and thereby avoids its induced numerical errors. In contrast to
      complicated implementations of conventional level set formulations, a simpler and
      more efficient finite difference scheme can be used to implement the DRLSE
      formulation. DRLSE also allows the use of more general and efficient
      initialization of the level set function. In its numerical implementation,
      relatively large time steps can be used in the finite difference scheme to reduce
      the number of iterations, while ensuring sufficient numerical accuracy. To
      demonstrate the effectiveness of the DRLSE formulation, we apply it to an edge
      based active contour model for image segmentation, and provide a simple
      narrowband implementation to greatly reduce computational cost.

PMID- 20801743
TI  - Minimization of monotonically levelable higher order MRF energies via graph cuts.
AB  - A feature of minimizing images of submodular binary Markov random field energies
      is introduced. Using this novel feature, the collection of minimizing images of
      levels of higher order, monotonically levelable multi label MRF energies is shown
      to constitute a monotone collection. This implies that these minimizing binary
      images can be combined to give minimizing images of the multi label MRF energies.
      Thanks to the graph cuts framework, the mentioned class of binary MRF energies is
      known to be minimized by maximum flow computations on appropriately constructed
      graphs. With the aid of these developments an exact and efficient algorithm to
      minimize monotonically levelable multi label MRF energies of any order, which is
      composed of a series of maximum flow computations, is proposed and an application
      of the proposed algorithm to image denoising is given. 

PMID- 20801744
TI  - A novel 3-D color histogram equalization method with uniform 1-D gray scale
      histogram.
AB  - The majority of color histogram equalization methods do not yield uniform
      histogram in gray scale. After converting a color histogram equalized image into
      gray scale, the contrast of the converted image is worse than that of an 1-D gray
      scale histogram equalized image. We propose a novel 3-D color histogram
      equalization method that produces uniform distribution in gray scale histogram by
      defining a new cumulative probability density function in 3-D color space. Test
      results with natural and synthetic images are presented to compare and analyze
      various color histogram equalization algorithms based upon 3-D color histograms.
      We also present theoretical analysis for nonideal performance of existing
      methods.

PMID- 20801745
TI  - Computational intelligent gait-phase detection system to identify pathological
      gait.
AB  - An intelligent gait-phase detection algorithm based on kinematic and kinetic
      parameters is presented in this paper. The gait parameters do not vary distinctly
      for each gait phase; therefore, it is complex to differentiate gait phases with
      respect to a threshold value. To overcome this intricacy, the concept of fuzzy
      logic was applied to detect gait phases with respect to fuzzy membership values.
      A real-time data-acquisition system was developed consisting of four force
      sensitive resistors and two inertial sensors to obtain foot-pressure patterns and
      knee flexion/extension angle, respectively. The detected gait phases could be
      further analyzed to identify abnormality occurrences, and hence, is applicable to
      determine accurate timing for feedback. The large amount of data required for
      quality gait analysis necessitates the utilization of information technology to
      store, manage, and extract required information. Therefore, a software
      application was developed for real-time acquisition of sensor data, data
      processing, database management, and a user-friendly graphical-user interface as
      a tool to simplify the task of clinicians. The experiments carried out to
      validate the proposed system are presented along with the results analysis for
      normal and pathological walking patterns.

PMID- 20801746
TI  - Australia revises its mortality data on suicide.

PMID- 20801747
TI  - A study of the Irish system of recording suicide deaths.
AB  - BACKGROUND: Many studies have examined the reliability of national suicide
      statistics. AIMS: To examine the Irish system of certifying suicide deaths and
      data collected by it. METHODS: Data were recorded from a police form (Form 104)
      completed and sent to the Irish Central Statistics Office (CSO) after all
      inquested deaths that occurred in Ireland in 2002. RESULTS: Of the approximately
      1,800 inquested deaths, 6% (and 4% of suicides) were not included in routine
      mortality statistics because of late registration. Of the 495 deaths thought by
      the police to be suicide, 485 (98%) were so recorded by the CSO. Information
      relating to medical history and contributory factors was provided in just 54% and
      34% of suicides, respectively. Suicide deaths showed significant variation by
      weekday (excess on Mondays) and calendar month (summer peak). The peak suicide
      rate (35 per 100,000) was among men aged 25-34 years. Persons separated, living
      alone, and unemployed had significantly elevated suicide rates. CONCLUSIONS:
      There is a need for a better understanding of national suicide recording systems,
      as this study has provided for Ireland. Such systems may routinely provide data
      relating to sociodemographic factors but not relating to medical and psychosocial
      factors.

PMID- 20801749
TI  - Repetition of suicide attempts: data from emergency care settings in five
      culturally different low- and middle-income countries participating in the WHO
      SUPRE-MISS Study.
AB  - BACKGROUND: Attempted suicide is a strong risk factor for subsequent suicidal
      behaviors. Innovative strategies to deal with people who have attempted suicide
      are needed, particularly in resource-poor settings. AIMS: To evaluate a brief
      educational intervention and periodic follow-up contacts (BIC) for suicide
      attempters in five culturally different sites (Campinas, Brazil; Chennai, India;
      Colombo, Sri Lanka; Karaj, Islamic Republic of Iran; and Yuncheng, People's
      Republic of China) as part of the WHO Multisite Intervention Study on Suicidal
      Behaviors (SUPRE-MISS). METHODS: Among the 1,867 suicide attempters enrolled in
      the emergency departments of the participating sites, 922 (49.4%) were randomly
      assigned to a brief intervention and contact (BIC) group and 945 (50.6%) to a
      treatment as usual (TAU) group. Repeated suicide attempts over the 18 months
      following the index attempt - the secondary outcome measure presented in this
      paper - were identified by follow-up calls or visits. Subsequent completed
      suicide - the primary outcome measure - has been reported in a previous paper.
      RESULTS: Overall, the proportion of subjects with repeated suicide attempts was
      similar in the BIC and TAU groups (7.6% vs. 7.5%, chi(2) = 0.013; p = .909), but
      there were differences in rates across the five sites. CONCLUSIONS: This study
      from five low- and middle-income countries does not confirm the effectiveness of
      brief educational intervention and follow-up contacts for suicide attempters in
      reducing subsequent repetition of suicide attempts up to 18 months after
      discharge from emergency departments.

PMID- 20801748
TI  - The acceptability of suicide among rural residents, urban residents, and college
      students from three locations in China: a cross-sectional survey.
AB  - BACKGROUND: Community attitudes about suicide and their relationship to suicidal
      behavior have not been adequately investigated in low- and middle-income
      countries. AIMS: To compare the acceptability of suicide in different population
      cohorts in China, identify factors that affect the degree of acceptability, and
      assess the relationship of cohort-specific acceptability of suicide and suicide
      rates. METHODS: A multistage stratified random sample of 608 rural residents, 582
      urban residents, and 629 college students were administered a 25-item scale
      studying the likelihood they would consider suicide (on a 5-point Likert scale)
      if they experienced a variety of stressors ranging from "being disciplined at
      work" to "developing a chronic mental illness." The internal consistency and test
      retest reliability for the scale are excellent (Cronbach's alpha = 0.92, ICC =
      0.75). RESULTS: College students had the most permissive attitudes about suicide,
      and urban residents were significantly more accepting of suicide as a response to
      serious life stressors than were rural residents. Multivariate analysis found
      that the overall acceptability score was higher in women, decreased with age, and
      increased with years of education. CONCLUSIONS: There was no clear relationship
      between cohort-specific acceptance of suicide and reported rates of suicide,
      highlighting the complexity of the relationship between attitudes about suicide
      (of which acceptability is only one component) and suicidal behavior.

PMID- 20801750
TI  - The impact of patient suicide on the professional reactions and practices of
      mental health caregivers and social workers.
AB  - BACKGROUND: Mental health and social professionals are at high risk of
      experiencing at least one patient suicide during their career. AIMS: This paper
      investigates the impact of patient suicide on the reactions and working practices
      of mental health and social professionals. It also examines how such an impact
      may vary depending on the professionals' characteristics, their relationship with
      the patient, as well as the institutional setting in which they work. METHODS:
      275 professionals working in sociomedical institutions in French-speaking
      Switzerland completed a questionnaire. RESULTS: Patient suicide can cause a wide
      range of long-lasting reactions and changes in the working practices of mental
      health and social professionals. Professional's gender, place of suicide, as well
      as responsibility for and emotional attachment to the patient significantly
      influence the impact that a patient suicide has on such professionals.
      Professional's age, the type of profession, the number of suicides experienced,
      and previous suicide attempts by the deceased patient were also found to play a
      significant role with regard to changes in working practices. CONCLUSIONS: Beyond
      the emotional and professional impact, patient suicide may have also a formative
      influence, encouraging professionals to review and improve their working
      practices. Recommendations to help mental health and social professionals who
      have experienced a patient suicide are discussed.

PMID- 20801751
TI  - Psychosocial assessment following self-harm: repetition of nonfatal self-harm
      after assessment by psychiatrists or mental health nurses.
AB  - BACKGROUND: Patients admitted to hospital because of self-harm should receive
      psychosocial assessment before discharge. In practice many of these assessments
      in the United Kingdom and elsewhere are undertaken by trainee rather than
      specialist psychiatrists. AIMS: To compare psychosocial assessments, aftercare,
      and the pattern of non-fatal repetition for patients admitted to general hospital
      after self-harm: comparing assessments carried out by trainee psychiatrists,
      allocated to the task alongside other duties on a roster, or by mental health
      nurses with a designated role in self-harm services. METHODS: Arrangements for
      aftercare and rates of non-fatal repetition of self-harm in 787 consecutive
      psychosocial assessments in a large UK city were compared, according to whether
      the assessments were carried out by trainee psychiatrists or mental health
      nurses. RESULTS: Compared with nurses, psychiatrists were much more likely to
      arrange psychiatric admission or outpatient follow-up. Nurses more often pointed
      people towards voluntary sector help - such as drug, alcohol or relationship
      counselling. Repetition of self-harm was equally common among those assessed by
      nurses or psychiatrists (33%; hazard ratio 0.93, 95% confidence interval 0.71 to
      1.2). CONCLUSIONS: Despite making fewer aftercare arrangements that involved
      statutory mental health care services, psychosocial assessment by mental health
      nurses showed no sign of detrimental effects on repetition of self-harm.

PMID- 20801752
TI  - Assessing the impact of suicide exclusion periods on life insurance.
AB  - BACKGROUND: We study the impact of suicide-exclusion periods, common in life
      insurance policies in Australia, on suicide and accidental death rates for life
      insured individuals. If a life-insured individual dies by suicide during the
      period of suicide exclusion, commonly 13 months, the sum insured is not paid.
      AIMS: We examine whether a suicide-exclusion period affects the timing of
      suicides. We also analyze whether accidental deaths are more prevalent during the
      suicide-exclusion period as life-insured individuals disguise their death by
      suicide. We assess the relationship between the insured sum and suicidal death
      rates. METHODS: Crude and age-standardized rates of suicide, accidental death,
      and overall death, split by duration since the insured first bought their
      insurance policy, were computed. RESULTS: There were significantly fewer suicides
      and no significant spike in the number of accidental deaths in the exclusion
      period for Australian life insurance data. More suicides, however, were detected
      for the first 2 years after the exclusion period. Higher insured sums are
      associated with higher rates of suicide. CONCLUSIONS: Adverse selection in
      Australian life insurance is exacerbated by including a suicide-exclusion period.
      Extension of the suicide-exclusion period to 3 years may prevent some "insurance
      induced" suicides - a rationale for this conclusion is given.

PMID- 20801757
TI  - Increasing breast examinations among arab women using a tailored culture-based
      intervention.
AB  - This study aimed to assess outcomes of a culture-specific intervention devised to
      reduce barriers to breast cancer screening among Arab women in Israel. Women in
      intervention (n = 42) and control (n = 24) groups answered breast examination
      performance and Arab culture-specific barriers and health beliefs questionnaires
      at pre- and postintervention. Women in the study group received tailored
      telephone intervention between the 2 interviews. Although the study and control
      groups did not differ in rate of attending clinical examinations and mammography
      at pre-intervention, at post-intervention, almost 48% of the intervention group
      and 12.5% of the control group scheduled or attended a clinical examination, and
      38.5% of women in the intervention group and 21.4% of the control group attended
      or scheduled a mammography. Of the cultural barriers, a significant group x time
      effect was found for the cultural barriers of exposure, social barriers, and self
      uneasiness with body, with a higher decrease in the intervention group. Of the
      health beliefs, a group x time effect was found for perceived vulnerability and
      perceived barriers to clinical examination and mammography, which significantly
      decreased in the intervention group, but not in the control group. The
      preliminary results showed that the culture-based intervention was effective in
      reducing barriers and increasing the rate of breast cancer examinations.

PMID- 20801755
TI  - Impact of defensive hostility in cardiovascular disease.
AB  - Among the psychosocial factors that may influence the development, maintenance,
      and progression of cardiovascular disease, defensive hostility as a possible risk
      factor has received substantial empirical support in recent years. The aim of our
      study was to analyze the relationship between defensive hostility and
      cardiovascular response to stress situations, as a better predictor of
      cardiovascular functioning than hostility alone. The sample was composed of 130
      female university students. The Cook-Medley Hostility Inventory (Ho) and the
      Spanish version (CRP) of the Marlowe-Crowne Social Desirability Scale (MC) were
      used to measure defensive hostility. We used the registration system MP150
      (Biopac) to measure the physiological variables throughout the 3 experimental
      phases (adaptation, task, and recovery). The stress task was a real exam. We
      expected cardiovascular responses, heart rate, and systolic and diastolic blood
      pressure to be higher in subjects with high hostility and high defensiveness in
      all 3 phases. The results reflect that individuals with high hostility and high
      defensiveness present the highest values in the physiological variables, thus
      supporting the hypothesis that defensive hostility shows the greatest predictive
      power in relation to cardiovascular functioning in stressful situations.

PMID- 20801756
TI  - Psychological factors associated with poor sleep prior to breast surgery: an
      exploratory study.
AB  - This study explored the relationship between psychological factors (including
      intrusive thoughts, anxiety, well-being, depressed mood) and poor sleep the night
      before surgery. Patients (N = 39) scheduled for breast surgery (mean age = 47
      years) wore an actiwatch at home the night before surgery to provide an objective
      indication of sleep duration and sleep efficiency. Participants also completed 3
      measures of their psychological experience during the week prior to surgery. In
      separate regression analyses, intrusive thoughts, anxiety, and emotional well
      being were each related to sleep duration the night before surgery, when
      controlling for age, body mass index, ethnicity, and marital status. No
      relationships were found between depressed mood, physical or social well-being,
      and sleep duration. In a multiple regression model that included all significant
      variables, intrusive thoughts were most strongly associated with sleep duration.
      Intrusive thoughts were also significantly related to sleep efficiency. Results
      suggest that patients' intrusions about impending surgery are associated with
      lower sleep duration and sleep efficiency the night before surgery. Additional
      research is warranted to explore the implications of these associations for
      patients, as well as possible interventions to improve sleep in this clinical
      setting.

PMID- 20801758
TI  - Sociocognitive factors associated with nonadherence to medication after hospital
      discharge.
AB  - Poor adherence to prescribed medication is a well-known problem and continues to
      be a major challenge in all medical specialties. Unlike previous studies that
      have mainly focused on nonadherence behaviors in specific diseases, this study
      sought to examine socio-cognitive factors associated with nonadherence behavior
      in a sample of a general clinical population. A questionnaire investigating socio
      demographic and cognitive factors and a telephone follow-up interview were
      administered to 84 patients recruited in a General Medicine Unit before their
      discharge. Half of the participants were informed about that follow-up procedure.
      One month after hospital discharge, 42% of uninformed patients reported
      nonadherence behaviors, as against 21% of informed patients. Middle-aged patients
      and short-term treatments were associated significantly more often with
      nonadherence. Among cognitive factors, patients' perceived risks and benefits of
      nonadherence, personal susceptibility to diseases, subjective health value, and
      reported memory failures were significantly associated with adherence. We
      conclude that a patient's perception may be more important than medication load,
      illness severity, and complexity of regimen in influencing medication adherence,
      and that a telephone call follow-up helps in monitoring medication adherence
      after hospital discharge.

PMID- 20801759
TI  - Lack of alpha-xylosidase activity in Arabidopsis alters xyloglucan composition
      and results in growth defects.
AB  - Xyloglucan is the main hemicellulose in the primary cell walls of most seed
      plants and is thought to play a role in regulating the separation of cellulose
      microfibrils during growth. Xylose side chains block the degradation of the
      backbone, and alpha-xylosidase activity is necessary to remove them. Two
      Arabidopsis (Arabidopsis thaliana) mutant lines with insertions in the alpha
      xylosidase gene AtXYL1 were characterized in this work. Both lines showed a
      reduction to undetectable levels of alpha-xylosidase activity against xyloglucan
      oligosaccharides. This reduction resulted in the accumulation of XXXG and XXLG in
      the liquid growth medium of Atxyl1 seedlings. The presence of XXLG suggests that
      it is a poor substrate for xyloglucan beta-galactosidase. In addition, the
      polymeric xyloglucan of Atxyl1 lines was found to be enriched in XXLG subunits,
      with a concomitant decrease in XXFG and XLFG. This change can be explained by
      extensive exoglycosidase activity at the nonreducing ends of xyloglucan chains.
      These enzymes could thus have a larger role than previously thought in the
      metabolism of xyloglucan. Finally, Atxyl1 lines showed a reduced ability to
      control the anisotropic growth pattern of different organs, pointing to the
      importance of xyloglucan in this process. The promoter of AtXYL1 was shown to
      direct expression to many different organs and cell types undergoing cell wall
      modifications, including trichomes, vasculature, stomata, and elongating anther
      filaments.

PMID- 20801760
TI  - Maintenance of certification: where we are, why we are here, and where we need to
      be.

PMID- 20801761
TI  - Posterior circulation and high prevalence of ischemic stroke among young
      pediatric patients with Moyamoya disease: evidence of angiography-based
      differences by age at diagnosis.
AB  - BACKGROUND AND PURPOSE: At diagnosis, the primary clinical manifestations of
      pediatric Moyamoya disease are TIA or CSs. CSs are reported to be more prevalent
      in younger than in older children. We sought to determine whether age-related
      differences in clinical manifestations are associated with age-related
      angiographic differences. MATERIALS AND METHODS: We divided 78 patients diagnosed
      with Moyamoya disease before 16 years of age into four 4-year age groups and
      examined the relationships between age at diagnosis and clinical manifestations
      and angiographic and MR imaging findings. RESULTS: Among the 4 diagnostic age
      groups, in those younger than 4 years of age, the prevalence of CSs and of
      infarctions on MR images was highest, and along with severity of steno-occlusive
      lesions of the PCA, the prevalence was significantly higher than that in the next
      diagnostic age group (4-7 years), though the severity of steno-occlusive lesions
      in the ICA and the degree of transdural collaterals did not differ significantly.
      The prevalence of CSs and infarctions did not differ significantly in the 3
      oldest diagnostic age groups, whereas ICA and PCA lesions and transdural
      collaterals correlated positively with diagnostic age. CONCLUSIONS: The high
      prevalence of CSs and infarctions in patients diagnosed before 4 years of age is
      associated with advanced steno-occlusive lesions of the PCA. In patients 4 years
      of age and older at diagnosis, transdural collaterals develop in parallel with
      advancement of ICA and PCA lesions, which may contribute to the nearly constant
      prevalence of CSs.

PMID- 20801762
TI  - Abnormal axial diffusivity in the deep gray nuclei and dorsal brain stem in
      infantile spasm treated with vigabatrin.
AB  - We evaluated the DTI changes in the deep gray nuclei and dorsal brain stem, which
      demonstrated abnormal T2 and/or diffusion signal intensity, in 6 patients with
      infantile spasm treated with vigabatrin compared with 6 age-matched controls.
      Regions of interest were placed in the globi pallidi, thalami, and dorsal brain
      stem; FA, trace, D(||), and D(?) were measured. Patients on vigabatrin had
      significantly lower FA in both globi pallidi (P = .01) and the dorsal brain stem
      (P < .01), significantly lower trace in both globi pallidi (P = .01) and the
      thalami (P = .02 and .01 for right and left, respectively), and significantly
      lower D(||) in both globi pallidi (P <= .01), the thalami (P < .01), and the
      dorsal brain stem (P = .03). There were no significant differences in D(?) of the
      globi pallidi, thalami, or dorsal brain stem in patients compared with controls.
      The findings suggest that axonal changes play a greater role in the observed
      abnormal signal intensity, with lesser contribution from myelin changes.

PMID- 20801763
TI  - MR spectroscopy findings in early stages of motor neuron disease.
AB  - BACKGROUND AND PURPOSE: Upper motor neuron degeneration varies in different
      phenotypes of MND. We used single-voxel MR spectroscopy of the primary motor
      cortex to detect corticomotoneuron degeneration and glial hyperactivity in
      different phenotypes of MND with a relatively short disease duration,
      contributing to further delineation of the phenotypes. MATERIALS AND METHODS: We
      prospectively included patients with ALS-B, ALS-L, and PMA and compared their
      data with those of patients with PLS and healthy controls. Each cohort consisted
      of 12 individuals. Disease duration was <1 year in ALS and PMA, but longer in PLS
      by definition. Follow-up examination was at 6 months. We measured ALSFRS-R,
      finger- and foot-tapping speed, and levels of the following: 1) NAAx, 2) mIns,
      and 3) Glx in the primary motor cortex. RESULTS: At baseline, we found
      significantly decreased NAAx levels and increased mIns levels in PLS. Levels of
      NAAx and mIns in patients with ALS-L and ALS-B were not significantly different
      from those in controls, but NAAx levels were significantly lower compared with
      those in PMA. At follow-up, only in PMA was a decrease of NAAx demonstrated. Glx
      levels varied widely in all groups. Levels of NAAx and mIns correlated well with
      clinical variables. CONCLUSIONS: Metabolite changes suggest neuronal dysfunction
      and active glial involvement in PLS. The corticomotoneuron is affected in early
      ALS-B and ALS-L, but at a later stage also in PMA. MR spectroscopy data are
      useful to obtain insight into the disease process at the level of the upper motor
      neuron in various phenotypes of MND.

PMID- 20801764
TI  - Injury to the vertebral endplate-disk complex associated with osteoporotic
      vertebral compression fractures.
AB  - BACKGROUND AND PURPOSE: MR imaging has been used extensively for identification
      and determination of chronicity of VCF. A major emphasis is placed on
      identification of edema or fluid clefts within the vertebral body. Little
      attention is given to other spinal structures such as vertebral endplate,
      intervertebral disk, posterior elements, and facet joints, spinal ligaments, and
      paraspinal musculature. Our objective was to assess the incidence of vertebral
      endplate and adjacent-level intervertebral disk injury as seen on MR imaging
      studies of patients with acute or subacute painful osteoporotic vertebral
      compression fractures. MATERIALS AND METHODS: We performed a retrospective review
      of spine MR imaging examinations in all patients who presented to our institution
      for subsequent treatment with vertebral augmentation. One hundred six patients
      had MR imaging studies and reports available for review. A total of 211 acute or
      subacute vertebral compression fractures were identified in this group of
      patients. All fracture levels were evaluated for the presence or absence of
      vertebral endplate and/or associated intervertebral disk injury. RESULTS:
      Detailed analysis of the images showed a high incidence of endplate and
      intervertebral disk injury. Superior vertebral endplate injury (39%) was more
      common than inferior endplate injury (12%), while the combination of both was
      observed in 29% of the levels. The pattern of intervertebral disk injury was
      similar, with injury to the disk above the fracture (36%) more common than injury
      to the disk below the fracture level (15%). While the official radiology reports
      correctly identified the vertebral compression fractures, they did not mention or
      describe the associated vertebral endplate or disk abnormalities. CONCLUSIONS:
      Vertebral endplate injury is commonly seen in osteoporotic vertebral compression
      fractures. Furthermore, this is frequently associated with injury to the adjacent
      intervertebral disk. These findings are often under-reported but should be
      described because they may have important implications for symptomatic
      presentation, patient management, and outcomes.

PMID- 20801765
TI  - CT-guided cervical selective nerve root block with a dorsal approach.
AB  - BACKGROUND AND PURPOSE: Cervical transforaminal blocks are frequently performed
      to treat cervical radicular pain. These blocks are performed mostly under
      fluoroscopy, but a CT-guided technique has also been described. The aim of this
      study was to review the results of CT-guided CSNRB by using a dorsal approach, to
      describe the contrast patterns achieved with this injection technique, and to
      estimate the degree of specificity and sensitivity. MATERIALS AND METHODS: We
      used a CT-guided technique with a dorsal approach leading to a more extra-than
      transforaminal but a selective nerve root block as well. Of 53 blocks, we
      performed 38 for diagnostic and 15 for therapeutic indications. Pain relief was
      measured hourly on a VAS. The distribution of contrast and the angle of the
      trajectory of the injection needle were analyzed as well as the degree of pain
      relief. RESULTS: Contrast was found in the intraforaminal region in 8 (15%)
      blocks, extraforaminally in 40 (78%) blocks, and intraspinally in 3 (6%) blocks.
      The mean angle between the needle and the sagittal plane was 26.6 degrees 
      (range, from 1 degrees  to 50 degrees ). The mean distance between needle tip and
      nerve root was 4.43 mm (range, 0-20 mm). Twenty-six (68.4%) of the 38 diagnostic
      blocks led to a decrease in the pain rating of >50%. There were no complications
      or unintended side effects, apart from occasional local puncture pain.
      CONCLUSIONS: We conclude that CT-guided CSNRBs using a dorsal approach are
      feasible and that they are sensitive and specific.

PMID- 20801766
TI  - Functional MR imaging in patients with carotid artery stenosis before and after
      revascularization.
AB  - BACKGROUND AND PURPOSE: Significant extracranial stenosis of the ICA is a known
      risk factor for future stroke and it has been shown that revascularization
      reduces the risk of future stroke. We applied BOLD fMRI in patients with carotid
      artery stenosis before and after CEA. Our purpose was to determine whether fMRI
      is able to demonstrate impaired CVR and to identify patient parameters that are
      associated with postoperative changes of cerebral hemodynamics. MATERIALS AND
      METHODS: Nineteen consecutive patients with symptomatic (n = 13) and asymptomatic
      (n = 6) stenosis of the ICA were prospectively recruited (male/female ratio =
      16:3; age, 69 +/- 8,1 years). fMRI using a simple bilateral motor task was
      performed immediately before and after CEA. RESULTS: Mean BOLD MSC was
      significantly increased postoperatively (MSC, 0.13 +/- 0.66; P = 0.0002).
      Patients with a stenosis of <80% demonstrated an increase in MSC (MSC, 0.32 +/-
      0.59; P <= .0001). Patients with previous ischemic stroke showed a larger MSC
      than patients with TIAs (stroke: MSC, 0.55 +/- 0.65; P <= .0001; TIA: MSC, 0.05
      +/- 0.26; P = 0.054). Patients older than 70 years had a significantly larger MSC
      following surgery (<=70 years: MSC, -0.01 +/- 0.39; P = .429; >70 years: MSC,
      0.29 +/- 0.48; P <= .0001). CONCLUSIONS: BOLD fMRI can demonstrate changes in
      cerebral hemodynamics before and after CEA, indicative of an ameliorated CVR.
      This response is dependent on the age of the patient, the degree of preoperative
      stenosis, and the patient's symptoms.

PMID- 20801767
TI  - Bringing forward reperfusion with oxygenated blood perfusion beyond arterial
      occlusion during endovascular procedures in patients with acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: High recanalization rates achieved with endovascular
      procedures are not always followed by the expected clinical improvement. These
      time-consuming procedures imply a delayed reperfusion despite the capacity of
      earlier intravascular microcatheter bypass to the ischemic tissue beyond the
      clot. We aimed to explore the safety and feasibility of MOB beyond the clot.
      MATERIALS AND METHODS: We studied patients with stroke undergoing endovascular
      procedures. The timing of procedural steps was recorded. We then explored the
      safety and feasibility of repeated femoral artery MOB injections beyond the
      occlusion every time the clot was crossed in 17 patients. Pre- and postocclusion
      flow was continuously monitored with TCD. RESULTS: We studied 60 patients (mean
      age, 70 +/- 11 years; median NIHSS score, 20; IR, 18-21). Of them, 33 (55%)
      received IV-tPA before the endovascular procedure. The following arteries were
      occluded: the MCA (63.3%, n = 38) and the ICA (36.6%, n = 22). The TSO to
      arterial puncture was 193 +/- 77 minutes. The occluding clot was successfully
      crossed with the microcatheter in 46 patients (76.6%; mean TSO, 228 +/- 82
      minutes). Recanalization was achieved in 44 patients (73.2%; mean TSO, 328 +/-
      144 minutes). Repeated MOB injections were performed in 17 patients. Patients
      with/without MOB presented with similar baseline characteristics. The median
      number of MOB injections was 2 (IR, 2-3), and the median injected blood volume
      was 40 mL (IR, 27.5-50). The mean time from first MOB to arterial recanalization
      was 136 +/- 86 minutes. During MOB, a nonpulsatile flow appeared in previously
      nonvisible distal branches on TCD. CONCLUSIONS: In this small series, oxygenated
      blood delivered through a microcatheter positioned distal to the site of
      occlusion was feasible and safe. Until final recanalization is achieved, MOB
      injections may generate intermittent reperfusion for up to 2 hours.

PMID- 20801768
TI  - RPL30 regulation of splicing reveals distinct roles for Cbp80 in U1 and U2 snRNP
      cotranscriptional recruitment.
AB  - Pre-mRNA splicing is catalyzed by the spliceosome, and its control is essential
      for correct gene expression. While splicing repressors typically interfere with
      transcript recognition by spliceosomal components, the yeast protein L30 blocks
      spliceosomal rearrangements required for the engagement of U2 snRNP (small
      ribonucleoprotein particle) to its own transcript RPL30. Using a mutation in the
      RPL30 binding site that disrupts this repression, we have taken a genetic
      approach to reveal that regulation of splicing is restored in this mutant by
      deletion of the cap-binding complex (CBC) component Cbp80. Indeed, our data
      indicate that Cbp80 plays distinct roles in the recognition of the intron by U1
      and U2 snRNP. It promotes the initial 5' splice site recognition by U1 and,
      independently, facilitates U2 recruitment, depending on sequences located in the
      vicinity of the 5' splice site. These results reveal a novel function for CBC in
      splicing and imply that these molecular events can be the target of a splicing
      regulator.

PMID- 20801769
TI  - ncRNAimprint: a comprehensive database of mammalian imprinted noncoding RNAs.
AB  - Imprinted noncoding RNAs (ncRNAs) are expressed mono-allelically in a parent-of
      origin-dependent manner, which is mainly evident in mammals. Lying at a crossroad
      between imprinted genes and ncRNAs, imprinted ncRNAs show distinct features. They
      are likely to function in nontraditional ways compared to non-imprinted ncRNAs,
      and are much more responsible for the mechanism of genomic imprinting compared to
      imprinted protein-coding genes. An increasing number of human diseases have been
      shown to be related to abnormalities in imprinted ncRNAs. Due to their functional
      importance, many studies focusing on imprinted ncRNAs have been published in
      recent years; however, there is no systematic collection or description of
      imprinted ncRNAs and the rapidly growing knowledge is scattered in various
      places. Here, we describe a new database, ncRNAimprint, which serves as a
      comprehensive resource center for mammalian imprinted ncRNAs. A catalog of
      imprinted ncRNAs, including snoRNAs, microRNAs, piRNAs, siRNAs, antisense ncRNAs,
      and mRNA-like ncRNAs, was annotated in detail using information extracted from
      relevant literature and databases. Comprehensive collections of imprinted ncRNA
      related diseases, imprinting control regions (ICRs), and imprinted regions were
      manually compiled to provide resources for current research focusing on imprinted
      ncRNAs. Small RNA deep sequencing reads that fully matched within imprinted
      regions were also included to offer useful evidence in detecting novel imprinted
      ncRNAs and to aid in analyzing expression patterns of known imprinted ncRNAs. A
      search page including four effective search forms and two graphical browsers was
      created for rapid retrieval and visualization of these data. The imprinted ncRNA
      database is freely accessible at http://rnaqueen.sysu.edu.cn/ncRNAimprint.

PMID- 20801771
TI  - Faecal calprotectin, lactoferrin, M2-pyruvate kinase and S100A12 in severe
      ulcerative colitis: a prospective multicentre comparison of predicting outcomes
      and monitoring response.
AB  - OBJECTIVE: To compare four faecal markers for their ability to predict steroid
      refractoriness in severe paediatric ulcerative colitis (UC). Construct validity
      and responsiveness to change were also assessed. METHODS: This was a prospective
      multicentre cohort study. Stool samples from 101 children (13.3 + or - 3.6 years;
      Pediatric UC Activity Index (PUCAI) at admission 72 + or - 12 points) were
      obtained at the third day of intravenous steroid therapy. Repeated samples at
      discharge were obtained from 24 children. Predictive validity was assessed using
      diagnostic utility statistics to predict steroid failure (ie, the need for
      salvage treatment). Concurrent validity was assessed using correlational analysis
      with the following constructs: PUCAI, Lindgren and Seo scores, physician's global
      assessment, albumin, erythrocyte sedimentation rate and C-reactive protein (CRP).
      Responsiveness was assessed using test utility and correlational strategies.
      RESULTS: Median values (IQR) were very high at baseline for all four markers
      (calprotectin 4215 microg/g (2297-8808); lactoferrin 212 microg/g (114-328); M2
      pyruvate kinase (M2-PK) 363 U/g (119-3104); and S100A12 469 microg/g (193-1112)).
      M2-PK was numerically superior to the other three markers and CRP in predicting
      response to corticosteroid treatment (area under the receiver operating
      characteristic (ROC) curve 0.75 (95% CI 0.64 to 0.85; p<0.001) vs <0.65 for the
      others). However, it did not add to the predictive ability of the PUCAI (area
      under the ROC 0.81 (95% CI 0.73 to 0.89)). M2-PK also had the highest construct
      validity but with a modest mean correlation with all constructs (r=0.3; p<0.05).
      None of the markers was responsive to change (Spearman's rho correlation with
      change in the PUCAI <0.1; p>0.05, area under the ROC curve <0.65; p>0.05).
      CONCLUSIONS: The four markers were greatly elevated in severe paediatric UC. Only
      M2-PK had good construct and predictive validity, and none was responsive to
      change. The PUCAI, a simple clinical index, performed better than the faecal
      markers in predicting outcome following a course of intravenous corticosteroids
      in severe UC.

PMID- 20801772
TI  - Simple non-invasive fibrosis scoring systems can reliably exclude advanced
      fibrosis in patients with non-alcoholic fatty liver disease.
AB  - BACKGROUND: Accurate evaluation of liver fibrosis in patients with non-alcoholic
      fatty liver disease (NAFLD) is important to identify patients who may develop
      complications. The aim of this study was to compare the diagnostic performance of
      simple non-invasive tests in identifying advanced fibrosis among patients with
      biopsy-proven NAFLD. METHODS: Consecutive patients with biopsy proven NAFLD were
      recruited from the Newcastle Hospitals Fatty Liver Clinic from 2003 to 2009. The
      AST/ALT ratio, AST to platelet ratio index, BARD (weighted sum of BMI>28=1 point,
      AST/ALT ratio>0.8=2 points, diabetes=1 point), FIB-4 (agexAST (IU/l)/platelet
      count (x10(9)/litre)x radicalALT (IU/l)) and NAFLD fibrosis scores were
      calculated from blood tests taken at time of biopsy. RESULTS: 145 patients (82
      male (61%), mean age 51+ or -12 years) were included. The mean body mass index
      was 35+ or -5 kg/m(2). 73 subjects (50%) had diabetes. 93 patients (64%) had non
      alcoholic steatohepatitis. 27 (19%) had advanced fibrosis (Kleiner stage 3-4).
      The FIB-4 score had the best diagnostic accuracy for advanced fibrosis (area
      under receiver operator characteristic curve (AUROC) 0.86), followed by AST/ALT
      ratio (AUROC 0.83), NAFLD fibrosis score (AUROC 0.81), BARD (AUROC 0.77) and AST
      to platelet ratio index (AUROC 0.67). The AST/ALT ratio, BARD score, FIB-4 and
      NAFLD fibrosis scores had negative predictive values greater than 90% (93%, 95%,
      95% and 92% respectively). Positive predictive values were modest. In order to
      exclude advanced fibrosis liver biopsy could potentially be avoided in 69% with
      AST/ALT ratio, 62% with FIB-4, 52% with NAFLD fibrosis score and 38% with BARD.
      CONCLUSIONS: The ALT/AST ratio, FIB-4 and NAFLD fibrosis scores can reliably
      exclude advanced fibrosis in a high proportion of patients with NAFLD, allowing
      liver biopsy to be used in a more directed manner.

PMID- 20801773
TI  - Management of post-operative intestinal failure.

PMID- 20801776
TI  - Comment on 'Predicting the response to infliximab from trough serum levels'.

PMID- 20801775
TI  - Behavioural and new pharmacological treatments for constipation: getting the
      balance right.
AB  - Chronic constipation affects almost one in six adults and is even more frequent
      in the elderly. In the vast majority of patients, there is no obstructive mucosal
      or structural cause for constipation and, after excluding relatively rare
      systemic diseases (commonest of which is hypothyroidism), the differential
      diagnosis is quickly narrowed down to three processes: evacuation disorder of the
      spastic (pelvic floor dyssynergia, anismus) or flaccid (descending perineum
      syndrome) varieties, and normal or slow transit constipation. Treatment of
      chronic constipation based on identifying the underlying pathophysiology is
      generally successful with targeted therapy. The aims of this review are to
      discuss targeted therapy for chronic constipation: behavioural treatment for
      outlet dysfunction and pharmacological treatment for constipation not associated
      with outlet dysfunction. In particular, we shall review the evidence that
      behavioural treatment works for evacuation disorders, describe the new treatment
      options for constipation not associated with evacuation disorder, and demonstrate
      how 'targeting therapy' to the underlying diagnosis results in a balanced
      approach to patients with these common disorders.

PMID- 20801777
TI  - Treatment of Helicobacter pylori infection.

PMID- 20801778
TI  - Antibiotic prophylaxis in gastrointestinal endoscopy.

PMID- 20801780
TI  - The Swedish Web-system for enhancement and development of evidence-based care in
      heart disease evaluated according to recommended therapies (SWEDEHEART).
AB  - AIMS: The aims of the Swedish Web-system for Enhancement and Development of
      Evidence-based care in Heart disease Evaluated According to Recommended Therapies
      (SWEDEHEART) are to support the improvement of care and evidence-based
      development of therapy of coronary artery disease (CAD). INTERVENTIONS: To
      provide users with online interactive reports monitoring the processes of care
      and outcomes and allowing direct comparisons over time and with other hospitals.
      National, regional and county-based reports are publicly presented on a yearly
      basis. SETTING: Every hospital (n=74) in Sweden providing the relevant services
      participates. Launched in 2009 after merging four national registries on CAD.
      POPULATION: Consecutive acute coronary syndrome (ACS) patients, and patients
      undergoing coronary angiography/angioplasty or heart surgery. Includes
      approximately 80, 000 new cases each year. STARTPOINTS: On admission in ACS
      patients, at coronary angiography in patients with stable CAD. BASELINE DATA: 106
      variables for patients with ACS, another 75 variables regarding secondary
      prevention after 12-14 months, 150 variables for patients undergoing coronary
      angiography/angioplasty, 100 variables for patients undergoing heart surgery.
      DATA CAPTURE: Web-based registry with all data registered online directly by the
      caregiver. DATA QUALITY: A monitor visits approximately 20 hospitals each year.
      In 2007, there was a 96% agreement. ENDPOINTS AND LINKAGES TO OTHER DATA: Merged
      with the National Cause of Death Register, including information about vital
      status of all Swedish citizens, the National Patient Registry, containing
      diagnoses at discharge for all hospital stays in Sweden and the National Registry
      of Drug prescriptions recording all drug prescriptions in Sweden. ACCESS TO DATA:
      Available for research by application to the SWEDEHEART steering group.

PMID- 20801782
TI  - Safety of etravirine in HIV-1/hepatitis B and/or C virus co-infected patients:
      pooled 96 week results from the Phase III DUET trials.
AB  - OBJECTIVES: Human immunodeficiency virus (HIV)-infected patients are frequently
      co-infected with hepatitis B and/or C virus (HBV/HCV). The safety of etravirine
      was investigated over 96 weeks in patients co-infected with HIV type-1 (HIV-1)
      and HBV and/or HCV in the Phase III DUET trials. DUET-1 and DUET-2 are registered
      with clinicaltrials.gov (NCT00254046 and NCT00255099, respectively). METHODS:
      Treatment-experienced, HIV-1-infected patients with documented non-nucleoside
      reverse transcriptase inhibitor (NNRTI) resistance were randomized to receive
      either etravirine 200 mg or placebo, both twice daily plus a background regimen
      of darunavir/ritonavir, investigator-selected nucleoside reverse transcriptase
      inhibitors and optional enfuvirtide. Hepatitis co-infection status was confirmed
      by hepatitis B surface antigen or HCV antibody and qualitative HCV RNA. Co
      infected patients were eligible if they did not require anti-hepatitis treatment
      and were clinically stable, with aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT) concentrations <5* the upper limit of normal. Adverse
      events (AEs) and laboratory parameters were analysed. RESULTS: Data were
      available for 566 etravirine- and 564 placebo-treated patients, of whom 72 (13%)
      and 68 (12%), respectively, were co-infected with HBV/HCV. Irrespective of co
      infection status, the etravirine and placebo groups were comparable for the
      incidence of grade 3/4 AEs [co-infected: 31 (43%) versus 31 (46%) patients,
      respectively; non-co-infected: 200 (40%) versus 176 (35%), respectively] and
      serious AEs [co-infected: 25 (35%) versus 25 (37%), respectively; non-co
      infected: 123 (25%) versus 119 (24%), respectively]. Consistent with the
      underlying hepatitis, relative to non-co-infected patients the co-infected
      patients, had a higher incidence of hepatic AEs [co-infected: 13 (18%) etravirine
      treated versus 10 (15%) placebo-treated patients; non-co-infected: 36 (7%) versus
      32 (6%), respectively], and grade 3/4 elevation of AST [co-infected: 8 (11%)
      versus 5 (7%), respectively; non-co-infected: 14 (3%) versus 9 (2%),
      respectively] and ALT [co-infected: 10 (14%) versus 6 (9%), respectively; non-co
      infected: 14 (3%) versus 8 (2%), respectively]. Discontinuation due to hepatic
      AEs was low and comparable between the treatment groups, regardless of co
      infection status (two co-infected patients in each treatment group; five
      etravirine-treated versus two placebo-treated non-co-infected patients).
      CONCLUSIONS: Etravirine demonstrated a similar safety profile to placebo in the
      subgroup of patients co-infected with HIV and HBV and/or HCV in the DUET trials.
      The incidence and severity of AEs with etravirine was generally comparable to
      placebo irrespective of co-infection status.

PMID- 20801783
TI  - In vitro activity of ceftazidime+NXL104 against Pseudomonas aeruginosa and other
      non-fermenters.
AB  - BACKGROUND: NXL104 potentiates ceftazidime and ceftaroline against
      Enterobacteriaceae with extended-spectrum, AmpC, KPC and OXA beta-lactamases. We
      examined whether similar potentiation was obtained against non-fermenters, which
      are less permeable than Enterobacteriaceae and have more potent efflux. METHODS:
      MICs of ceftazidime+NXL104 (with NXL104 at 4 mg/L) and comparators were
      determined by CLSI agar dilution for: (i) Pseudomonas aeruginosa AmpC mutants and
      extended-spectrum beta-lactamase (ESBL)-producing transconjugants; (ii) clinical
      P. aeruginosa isolates with AmpC enzymes, ESBLs or up-regulated efflux; (iii) P.
      aeruginosa and Burkholderia cepacia complex isolates from cystic fibrosis
      patients; and (iv) Acinetobacter baumannii with OXA carbapenemases, which also
      compromise ceftazidime. RESULTS: NXL104 reversed AmpC-mediated ceftazidime
      resistance in P. aeruginosa, reducing MICs for fully derepressed mutants and
      isolates to <= 8 mg/L. NXL104 also reversed ceftazidime resistance caused by the
      ESBL PER-1, but not that due to OXA ESBLs or VEB-1 enzyme. Efflux-mediated
      resistance was unaffected. Resistance to ceftazidime in isolates of P. aeruginosa
      and the B. cepacia complex from patients with cystic fibrosis was variably
      overcome, generally to greater effect for B. cepacia. NXL104 had little effect on
      MICs of ceftazidime for A. baumannii isolates with OXA carbapenemases.
      CONCLUSIONS: The potentiation of ceftazidime against many beta-lactamase
      producing P. aeruginosa and B. cepacia complex strains confirms that NXL104
      penetrates these organisms. The utility of the combination against these
      pathogens will depend on the local prevalence of strains with beta-lactamase-
      versus efflux-mediated resistance. The lack of potentiation against A. baumannii
      may reflect failure of NXL104 to penetrate these bacteria to inhibit relevant
      (OXA-23, -40, -51 and -58) carbapenemases.

PMID- 20801781
TI  - Down-regulation of porin M35 in Moraxella catarrhalis by aminopenicillins and
      environmental factors and its potential contribution to the mechanism of
      resistance to aminopenicillins.
AB  - OBJECTIVES: The outer membrane protein M35 of Moraxella catarrhalis is an
      antigenically conserved porin. Knocking out M35 significantly increases the MICs
      of aminopenicillins. The aim of this study was to determine the biological
      mechanism of this potentially new antimicrobial resistance mechanism of M.
      catarrhalis and the behaviour of M35 in general stress situations. METHODS: PCR
      using m35-specific primers was used to detect the m35 gene in clinical isolates.
      The m35 mRNA expression of strains 300, O35E and 415 after exposure to
      amoxicillin and different stress conditions was measured by real-time PCR and
      normalized in relation to their 16S rRNA expression. The expression of M35
      protein was analysed by SDS-PAGE and western blotting. RESULTS: Screening of 52
      middle ear isolates resulted in positive PCR products for all tested strains. The
      analysis of m35 mRNA expression after amoxicillin treatment showed 24%-85% down
      regulation compared with the respective amoxicillin-free controls in all three
      strains tested. Also, analysis of protein concentrations revealed lower M35
      expression after growth with amoxicillin. Investigation of M35 during general
      stress responses showed down-regulation of the porin with growth at 26 degrees C
      and 42 degrees C, under hyperosmolar stress and under iron restriction.
      CONCLUSIONS: The reduced expression of M35 after aminopenicillin exposure
      indicates a novel resistance mechanism against aminopenicillins in M.
      catarrhalis, which may be relevant in vivo. The differences in expression after
      different stress treatments demonstrate that M35 is involved in general stress
      responses.

PMID- 20801850
TI  - Children deserve the same rights we do: the need for paediatric pulmonary
      arterial hypertension clinical drug development.

PMID- 20801851
TI  - Raising high-density lipoprotein: for better or worse?

PMID- 20801852
TI  - Transradial access for primary percutaneous coronary intervention: the next
      standard of care?
AB  - OBJECTIVE: Primary percutaneous coronary intervention (PPCI) has been
      acknowledged by the most recent European guidelines to be the preferred treatment
      for ST elevation myocardial infarction (STEMI). Patients undergoing PPCI are
      expected to receive a broad spectrum of anticoagulants and antiplatelet agents,
      which increases the risk of bleedings, in most cases, at the site of vascular
      access. The burden of bleeding complications after PPCI is as negative as that of
      ischemic complications not only on in-hospital morbidity, but also on mid- and
      long-term survival. Owing to the unique features of the radial artery,
      transradial approach (TRA) seems able to overcome most of the problems related to
      vascular access particularly in case of STEMI. In this short review we discuss
      the results of the latest studies and we highlight not only the safety and
      feasibility of TRA-PPCI, but also the advantages in terms of morbidity and
      mortality. We finally report on our experience at OLVG Amsterdam, and how TRA can
      also change the logistics in case of a PPCI programme (short stay).

PMID- 20801853
TI  - High-density lipoprotein cholesterol increase and non-cardiovascular mortality: a
      meta-analysis.
AB  - CONTEXT: Many observational prospective studies have confirmed the inverse
      relationship between high-density lipoprotein (HDL) cholesterol and coronary
      heart disease. However, the potential benefit of the pharmacological increase in
      HDL cholesterol has not been clearly demonstrated. Moreover, in some
      interventions an increase in total mortality has been reported. OBJECTIVE: The
      objective of this meta-analysis was to determine the relationship between HDL
      cholesterol increase and non-cardiovascular mortality in randomised trials. DATA
      SOURCES: Authors searched Medline up to December 2008. STUDY SELECTION: Four
      reviewers identified randomised trials in which, through different types of
      interventions, HDL cholesterol increase in the treatment group was >4% compared
      to control group, both groups reported separately non-cardiovascular mortality
      and the duration of the study was, at least, one year. DATA EXTRACTION: Data of
      HDL cholesterol concentrations and deaths were collected as they appeared in the
      original studies. If necessary, reviewers calculated data by using trial
      information. RESULTS: Meta-regression analysis included 44 articles corresponding
      to 107 773 participants. Analysis showed an association between HDL cholesterol
      increase and non-cardiovascular mortality (p=0.023), however, the correlation
      disappeared when we excluded the ILLUMINATE (Investigation of Lipid Level
      Management to Understand its Impact in Atherosclerosis Events) trial from the
      analysis (p=0.972). CONCLUSIONS: Meta-regression analysis results suggest that
      increases in HDL cholesterol up to 40% are not associated with higher non
      cardiovascular death. The increase in adverse events observed in some trials
      where HDL cholesterol was raised in large amounts could be related with the drug
      mechanisms more than the HDL cholesterol increase itself.

PMID- 20801854
TI  - Quantification of lumen stenoses with known dimensions by conventional
      angiography and computed tomography: implications of using conventional
      angiography as gold standard.
AB  - BACKGROUND: Quantitative coronary angiography (QCA) has inherent limitations for
      displaying complex vascular anatomy, yet it remains the gold standard for
      stenosis quantification. OBJECTIVE: To investigate the accuracy of stenosis
      assessment by multi-detector computed tomography (MDCT) and QCA compared to known
      dimensions. METHODS: Nineteen acrylic coronary vessel phantoms with precisely
      drilled stenoses of mild (25%), moderate (50%) and severe (75%) grade were
      studied with 64-slice MDCT and digital flat panel angiography. Fifty-seven
      stenoses of circular and non-circular shape were imaged with simulated cardiac
      motion (60 bpm). Image acquisition was optimised for both imaging modalities, and
      stenoses were quantified by blinded expert readers using electronic callipers
      (for MDCT) or lumen contour detection software (for QCA). RESULTS: Average
      difference between true and measured per cent diameter stenosis for QCA was
      similar compared to MDCT: 7 (+/-6)% vs 7 (+/-5)% (p=0.78). While QCA performed
      better than MDCT in stenoses with circular lumen (mean error 4 (+/-3)% vs 7 (+/
      6)%, p<0.01), MDCT was superior to QCA for evaluating stenoses with non-circular
      geometry (mean error 10 (+/-7)% vs 7 (+/-5)%, p<0.05). In such lesions, QCA
      underestimated the true diameter stenosis by >20% in 9 of 27 (33%) vs 1 of 29
      (3%) in lumen with circular geometry. CONCLUSIONS: QCA often underestimates
      diameter stenoses in lumen with non-circular geometry. Compared to QCA, MDCT
      yields mildly greater measurement errors in perfectly circular lumen but performs
      better in non-circular lesions. These findings have implications for using QCA as
      the gold standard for stenosis quantification by MDCT.

PMID- 20801855
TI  - Large thrombus burden in acute myocardial infarction: successful use of distal
      protection device following failure of thrombus aspiration.

PMID- 20801857
TI  - Prasugrel for the treatment of acute coronary syndromes with percutaneous
      coronary intervention: NICE technology appraisal guidance.

PMID- 20801856
TI  - Pulmonary venous isolation by antral ablation with a large cryoballoon for
      treatment of paroxysmal and persistent atrial fibrillation: medium-term outcomes
      and non-randomised comparison with pulmonary venous isolation by radiofrequency
      ablation.
AB  - BACKGROUND: To prevent atrial fibrillation (AF) recurrence after catheter
      ablation, pulmonary venous isolation (PVI) at an antral level is more effective
      than segmental ostial ablation. Cryoablation around the pulmonary venous (PV)
      ostia for AF therapy is potentially safer compared to radiofrequency ablation
      (RFA). The aim of this study was to investigate the efficacy of a strategy using
      a large cryoablation balloon to perform antral cryoablation with 'touch-up'
      ostial cryoablation for PVI in patients with paroxysmal and persistent AF.
      METHODS: Paroxysmal and persistent AF patients undergoing their first left atrial
      ablation were recruited. After cryoballoon therapy, each PV was assessed for
      isolation and if necessary, treated with focal ostial cryoablation until PVI was
      achieved. Follow-up with Holter monitoring was performed. Clinical outcomes of
      the cryoablation protocol were compared, with consecutive patients undergoing PVI
      by RFA. RESULTS: 124 consecutive patients underwent cryoablation. 77% of
      paroxysmal and 48% of persistent AF subjects were free from AF at 12 months after
      a single procedure. Over the same time period, 53 consecutive paroxysmal AF
      subjects underwent PVI with RFA and at 12 months, 72% were free from AF at 12
      months (p=NS). There were too few persistent AF subjects (n=8) undergoing solely
      PVI by RFA as a comparison group. Procedural and fluoroscopic times during
      cryoablation were significantly shorter than RFA. CONCLUSIONS: PV isolation can
      be achieved in less than 2 h by a simple cryoablation protocol with excellent
      results after a single intervention, particularly for paroxysmal AF.

PMID- 20801858
TI  - Echocardiography in the catheterisation laboratory.

PMID- 20801859
TI  - Acute and long term management of pulmonary embolism.

PMID- 20801860
TI  - Cardiac imaging training in the United Kingdom--time for a New Dawn.

PMID- 20801861
TI  - Coronary artery dilation in LEOPARD syndrome: surveillance with low radiation
      dose cardiac CT.

PMID- 20801862
TI  - Chest radiography of chronic rheumatic heart disease in 2010.

PMID- 20801863
TI  - Testing and estimating model-adjusted effect-measure modification using marginal
      structural models and complex survey data.
AB  - Recently, it has been shown how to estimate model-adjusted risks, risk
      differences, and risk ratios from complex survey data based on risk averaging and
      SUDAAN (Research Triangle Institute, Research Triangle Park, North Carolina). The
      authors present an alternative approach based on marginal structural models
      (MSMs) and SAS (SAS Institute, Inc., Cary, North Carolina). The authors estimate
      the parameters of the MSM using inverse weights that are the product of 2 terms.
      The first term is a survey weight that adjusts the sample to represent the
      unstandardized population. The second term is an inverse-probability-of-exposure
      weight that standardizes the population in order to adjust for confounding; it
      must be estimated using the survey weights. The authors show how to use the MSM
      parameter estimates and contrasts to test and estimate effect-measure
      modification; SAS code is provided. They also explain how to program the previous
      risk-averaging approach in SAS. The 2 methods are applied and compared using data
      from the 2007 Florida Behavioral Risk Factor Surveillance System Survey to assess
      effect modification by age of the difference in risk of cost barriers to health
      care between persons with disability and persons without disability.

PMID- 20801864
TI  - Epidemiology and risk factors of incident hepatitis E virus infections in rural
      Bangladesh.
AB  - Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the
      world. Most of South Asia is HEV endemic, with frequent seasonal epidemics of
      hepatitis E and continuous sporadic cases. This author group's epidemiologic work
      and clinical reports suggest that Bangladesh is HEV endemic, but there have been
      few population-based studies of this country's HEV burden. The authors calculated
      HEV infection rates, over an 18-month interval between 2003 and 2005, by
      following a randomly selected cohort of 1,134 subjects between the ages of 1 and
      88 years, representative of rural communities in southern Bangladesh. Baseline
      prevalence of antibody to hepatitis E virus (anti-HEV) was 22.5%. Seroincidence
      was 60.3 per 1,000 person-years during the first 12 months and 72.4 per 1,000
      person-years from >12 to 18 months (during the monsoon season), peaking by age 50
      years and with low rates during childhood. Few of the seroconverting subjects
      reported hepatitis-like illness. Overall incidence was calculated to be 64 per
      1,000 person-years, with 1,172 person-years followed. No significant associations
      were found between anti-HEV incidence and demographic or socioeconomic factors
      for which data were available. This is the first study to document annual HEV
      infection rates among "healthy" and very young to elderly subjects in a rural
      Bangladeshi population.

PMID- 20801866
TI  - Increases in energy intake, insulin resistance and stress in rats before Wenchuan
      earthquake far from the epicenter.
AB  - The study of pre-earthquake (PE) behavior in animals has always been shrouded by
      controversy. There is very little scientific evidence showing that animals can
      sense the coming of an earthquake and that their organisms undergo physiological
      changes during the PE period. On the day of the Wenchuan earthquake, prior to the
      time of its actual occurrence, we were coincidentally able to measure the insulin
      sensitivity and stress level in rats that were originally part of another study.
      We detected defects in insulin signaling and a decrease in glucose uptake in
      skeletal muscle (SkM) and adipose tissue (AT), indicating impaired insulin
      sensitivity. These changes were associated with significantly increased plasma
      corticosterone concentration and elevated HSD11B1 mRNA expression in SkM and AT.
      The increase in insulin resistance (IR) could be attributed to elevated local
      (SkM and AT) and systemic stress. Interestingly, we also noticed that the food
      intake in rats showed a sudden increase two days before the earthquake and
      reached a peak on the day of the earthquake itself. Our observations suggest the
      possibility that the rats underwent PE physiological changes consisting of an
      increase in the stress level and consequently leading to an increase in food
      intake and IR.

PMID- 20801865
TI  - Ethnic density and preterm birth in African-, Caribbean-, and US-born non
      Hispanic black populations in New York City.
AB  - Segregation studies suggest that the health of blacks in the United States is
      poorer in majority-black compared with mixed-race neighborhoods. However,
      segregation studies have not examined black immigrants, who may benefit from
      social support and country-of-origin foods in black immigrant areas. The authors
      used 1995-2003 New York City birth records and a spatial measure of ethnic
      density to conduct a cross-sectional investigation of the risks of preterm birth
      for African-, Caribbean-, and US-born non-Hispanic black women associated with
      neighborhood-level African-, Caribbean-, and US-born non-Hispanic black density,
      respectively. Preterm birth risk differences were computed from logistic model
      coefficients, comparing neighborhoods in the 90th percentile of ethnic density
      with those in the 10th percentile. African black preterm birth risks increased
      with African density, especially in more deprived neighborhoods, where the risk
      difference was 6.1 per 1,000 (95% confidence interval: 1.9, 10.2). There was
      little evidence of an ethnic density effect among non-Hispanic black Caribbeans.
      Among US-born non-Hispanic blacks, an increase in preterm birth risk associated
      with US-born black density was observed in more deprived neighborhoods only (risk
      difference = 12.5, 95% confidence interval: 6.6, 18.4). Ethnic density seems to
      be more strongly associated with preterm birth for US-born non-Hispanic blacks
      than for non-Hispanic black immigrants.

PMID- 20801867
TI  - Association of vascular endothelial growth factor -634C/G polymorphism and
      diabetic retinopathy in type 2 diabetic Han Chinese.
AB  - Genetic factors are important in the pathogenesis of diabetic retinopathy (DR);
      there is a clear association of increased expression of vascular endothelial
      growth factor (VEGF) with DR as well as numerous VEGF polymorphisms that are
      linked to increased VEGF levels and DR. In this study, the relationships between
      the VEGF promoter polymorphism -634C/G, plasma VEGF levels and DR were examined
      in the Han Chinese. Ninety-six healthy subjects and 285 subjects with type 2
      diabetes were enrolled in this study. The diabetic subjects were divided into
      three groups depending on the degree of DR as determined by fundus photography
      and fluorescent angiography. Along with standard clinical characteristics, the 
      634C/G polymorphism was examined using TaqMan allelic discrimination, and plasma
      VEGF levels were analyzed by enzyme-linked immunosorbent assay. The distribution
      of the polymorphism differed significantly between patients with and without
      retinopathy; this was most pronounced between the no DR and proliferative DR
      groups. Significantly greater plasma VEGF levels were present in those with the 
      634CC genotype, and only the proliferative DR group had elevated plasma VEGF
      levels. Logistic regression revealed that the -634C/G polymorphism is strongly
      associated with DR. This study suggests that diabetic Han Chinese carrying the 
      634CC VEGF promoter polymorphism have a genetic risk of DR, and this polymorphism
      may be a major factor influencing plasma VEGF levels. Therefore, this
      polymorphism may be used as a biomarker at the onset of diabetes in the Han
      Chinese to predict the risk of DR, allowing for clinicians to treat these
      patients more aggressively.

PMID- 20801868
TI  - Informatics in radiology: RADTF: a semantic search-enabled, natural language
      processor-generated radiology teaching file.
AB  - Storing and retrieving radiology cases is an important activity for education and
      clinical research, but this process can be time-consuming. In the process of
      structuring reports and images into organized teaching files, incidental
      pathologic conditions not pertinent to the primary teaching point can be omitted,
      as when a user saves images of an aortic dissection case but disregards the
      incidental osteoid osteoma. An alternate strategy for identifying teaching cases
      is text search of reports in radiology information systems (RIS), but retrieved
      reports are unstructured, teaching-related content is not highlighted, and
      patient identifying information is not removed. Furthermore, searching
      unstructured reports requires sophisticated retrieval methods to achieve useful
      results. An open-source, RadLex((r))-compatible teaching file solution called
      RADTF, which uses natural language processing (NLP) methods to process radiology
      reports, was developed to create a searchable teaching resource from the RIS and
      the picture archiving and communication system (PACS). The NLP system extracts
      and de-identifies teaching-relevant statements from full reports to generate a
      stand-alone database, thus converting existing RIS archives into an on-demand
      source of teaching material. Using RADTF, the authors generated a semantic search
      enabled, Web-based radiology archive containing over 700,000 cases with millions
      of images. RADTF combines a compact representation of the teaching-relevant
      content in radiology reports and a versatile search engine with the scale of the
      entire RIS-PACS collection of case material.

PMID- 20801869
TI  - Quality initiatives: department scorecard: a tool to help drive imaging care
      delivery performance.
AB  - The radiology department at a midwestern U.S. children's hospital has created a
      scorecard that is presented quarterly to the institutional leadership and is
      available to all radiology employees on the institutional intranet. The scorecard
      currently has 33 measures in six areas: clinical services (safety, quality,
      timeliness); education; research; professionalism, communication, and user
      satisfaction; finances and administration; and staffing. For each measure, the
      goal, current value of the measure, interval at which the measure is updated,
      date of last update, and previous value of the measure are listed. Each measure
      was reviewed over time to determine those measures for which target goals were
      met. Results indicate that a visible and transparent department scorecard is one
      of the more powerful tools available to the radiology leadership to call
      attention to and improve performance in specific areas. The use of such a
      scorecard can help develop a departmental culture of quality improvement, focus
      healthcare providers on specific quality improvement projects, and drive
      departmental performance.

PMID- 20801870
TI  - Mating pheromone in Cryptococcus neoformans is regulated by a
      transcriptional/degradative "futile" cycle.
AB  - Sexual reproduction in fungi requires induction of signaling pheromones within
      environments that are conducive to mating. The fungus Cryptococcus neoformans is
      currently the fourth greatest cause of infectious death in regions of Africa and
      undergoes mating in phytonutrient-rich environments to create spores with
      infectious potential. Here we show that under conditions where sexual development
      is inhibited, a ~17-fold excess of MFalpha pheromone transcript is synthesized
      and then degraded by a DEAD box protein, Vad1, resulting in low steady state
      transcript levels. Transfer to mating medium or deletion of the VAD1 gene
      resulted in high level accumulation of MFalpha transcripts and enhanced mating,
      acting in concert with the mating-related HOG1 pathway. We then investigated
      whether the high metabolic cost of this apparently futile transcriptional cycle
      could be justified by a more rapid induction of mating. Maintenance of Vad1
      activity on inductive mating medium by constitutive expression resulted in
      repressed levels of MFalpha that did not prevent but rather prolonged the time to
      successful mating from 5-6 h to 15 h (p < 0.0001). In sum, these data suggest
      that VAD1 negatively regulates the sexual cell cycle via degradation of
      constitutive high levels of MFalpha transcripts in a synthetic/degradative cycle,
      providing a mechanism of mRNA induction for time-critical cellular events, such
      as mating induction.

PMID- 20801871
TI  - Human alveolar type II cells secrete and absorb liquid in response to local
      nucleotide signaling.
AB  - A balance sheet describing the integrated homeostasis of secretion, absorption,
      and surface movement of liquids on pulmonary surfaces has remained elusive. It
      remains unclear whether the alveolus exhibits an intra-alveolar ion/liquid
      transport physiology or whether it secretes ions/liquid that may communicate with
      airway surfaces. Studies employing isolated human alveolar type II (AT2) cells
      were utilized to investigate this question. Human AT2 cells exhibited both
      epithelial Na(+) channel-mediated Na(+) absorption and cystic fibrosis
      transmembrane conductance regulator-mediated Cl(-) secretion, both significantly
      regulated by extracellular nucleotides. In addition, we observed in normal AT2
      cells an absence of cystic fibrosis transmembrane conductance regulator
      regulation of epithelial Na(+) channel activity and an absence of
      expression/activity of reported calcium-activated chloride channels (TMEM16A,
      Bestrophin-1, ClC2, and SLC26A9), both features strikingly different from normal
      airway epithelial cells. Measurements of alveolar surface liquid volume revealed
      that normal AT2 cells: 1) achieved an extracellular nucleotide concentration
      dependent steady state alveolar surface liquid height of ~4 MUm in vitro; 2)
      absorbed liquid when the lumen was flooded; and 3) secreted liquid when treated
      with UTP or forskolin or subjected to cyclic compressive stresses mimicking tidal
      breathing. Collectively, our studies suggest that human AT2 cells in vitro have
      the capacity to absorb or secrete liquid in response to local alveolar
      conditions.

PMID- 20801872
TI  - Heart-specific small subunit of myosin light chain phosphatase activates rho
      associated kinase and regulates phosphorylation of myosin phosphatase target
      subunit 1.
AB  - Phosphorylation of myosin regulatory light chain (MLC) plays a regulatory role in
      muscle contraction, and the level of MLC phosphorylation is balanced by MLC
      kinase and MLC phosphatase (MLCP). MLCP consists of a catalytic subunit, a large
      subunit (MYPT1 or MYPT2), and a small subunit. MLCP activity is regulated by
      phosphorylation of MYPTs, whereas the role of small subunit in the regulation
      remains unknown. We previously characterized a human heart-specific small subunit
      (hHS-M(21)) that increased the sensitivity to Ca(2+) in muscle contraction. In
      this study, we investigated the role of hHS-M(21) in the regulation of MLCP
      phosphorylation. Two isoforms of hHS-M(21), hHS-M(21)A and hHS-M(21)B,
      preferentially bound the C-terminal one-third region of MYPT1 and MYPT2,
      respectively. Amino acid substitutions at a phosphorylation site of MYPT1, Ser
      852, impaired the binding of MYPT1 and hHS-M(21). The hHS-M(21) increased the
      phosphorylation level of MYPT1 at Thr-696, which was attenuated by Rho-associated
      kinase (ROCK) inhibitors and small interfering RNAs for ROCK. In addition, hHS
      M(21) bound ROCK and enhanced the ROCK activity. These findings suggest that hHS
      M(21) is a heart-specific effector of ROCK and plays a regulatory role in the
      MYPT1 phosphorylation at Thr-696 by ROCK.

PMID- 20801873
TI  - Prolyl hydroxylase domain (PHD) 2 affects cell migration and F-actin formation
      via RhoA/rho-associated kinase-dependent cofilin phosphorylation.
AB  - Cells are responding to hypoxia via prolyl-4-hydroxylase domain (PHD) enzymes,
      which are responsible for oxygen-dependent hydroxylation of the hypoxia-inducible
      factor (HIF)-1alpha subunit. To gain further insight into PHD function, we
      generated knockdown cell models for the PHD2 isoform, which is the main isoform
      regulating HIF-1alpha hydroxylation and thus stability in normoxia. Induction of
      a PHD2 knockdown in tetracycline-inducible HeLa PHD2 knockdown cells resulted in
      increased F-actin formation as detected by phalloidin staining. A similar effect
      could be observed in the stably transfected PHD2 knockdown cell clones 1B6 and
      3B7. F-actin is at least in part responsible for shaping cell morphology as well
      as regulating cell migration. Cell migration was impaired significantly as a
      consequence of PHD2 knockdown in a scratch assay. Mechanistically, PHD2 knockdown
      resulted in activation of the RhoA (Ras homolog gene family member A)/Rho
      associated kinase pathway with subsequent phosphorylation of cofilin. Because
      cofilin phosphorylation impairs its actin-severing function, this may explain the
      F-actin phenotype, thereby providing a functional link between PHD2-dependent
      signaling and cell motility.

PMID- 20801874
TI  - Proline isomerase Pin1 represses terminal differentiation and myocyte enhancer
      factor 2C function in skeletal muscle cells.
AB  - Reversible proline-directed phosphorylation at Ser/Thr-Pro motifs has an
      essential role in myogenesis, a multistep process strictly regulated by several
      signaling pathways that impinge on two families of myogenic effectors, the basic
      helix-loop-helix myogenic transcription factors and the MEF2 (myocyte enhancer
      factor 2) proteins. The question of how these signals are deciphered by the
      myogenic effectors remains largely unaddressed. In this study, we show that the
      peptidyl-prolyl isomerase Pin1, which catalyzes the isomerization of
      phosphorylated Ser/Thr-Pro peptide bonds to induce conformational changes of its
      target proteins, acts as an inhibitor of muscle differentiation because its
      knockdown in myoblasts promotes myotube formation. With the aim of clarifying the
      mechanism of Pin1 function in skeletal myogenesis, we investigated whether MEF2C,
      a critical regulator of the myogenic program that is the end point of several
      signaling pathways, might serve as a/the target for the inhibitory effects of
      Pin1 on muscle differentiation. We show that Pin1 interacts selectively with
      phosphorylated MEF2C in skeletal muscle cells, both in vitro and in vivo. The
      interaction with Pin1 requires two novel critical phospho-Ser/Thr-Pro motifs in
      MEF2C, Ser(98) and Ser(110), which are phosphorylated in vivo. Overexpression of
      Pin1 decreases MEF2C stability and activity and its ability to cooperate with
      MyoD to activate myogenic conversion. Collectively, these findings reveal a novel
      role for Pin1 as a regulator of muscle terminal differentiation and suggest that
      Pin1-mediated repression of MEF2C function could contribute to this function.

PMID- 20801875
TI  - Zyxin-mediated actin assembly is required for efficient wound closure.
AB  - Cytoskeletal regulation of cell adhesion is vital to the organization of
      multicellular structures. The focal adhesion protein zyxin emerged as a key
      regulator of actin assembly because zyxin recruits Enabled/vasodilator-stimulated
      phospho-proteins (Ena/VASP) to promote actin assembly. Zyxin also localizes to
      the sites of cell-cell adhesion and is thought to promote actin assembly with
      Ena/VASP. Using shRNA targeted to zyxin, we analyzed the roles of zyxin at
      adhesive contacts. In zyxin-deficient cells, the actin assembly at both focal
      adhesion and cell-cell adhesion was limited, but their migration rate was
      unchanged. Cell spreading on E-cadherin-coated surfaces and the formation of cell
      clusters were slower for zyxin-deficient cells than wild type cells. By ablating
      a single cell within a cell monolayer, we quantified the rate of wound closure
      driven by a contractile circumferential actin ring. Zyxin-deficient cells failed
      to recruit VASP to cell-cell junctions at the wound edge and had a slower wound
      closure rate than wild type cells. Our results suggest that, by recruiting VASP,
      zyxin regulates actin assembly at the sites of force-bearing cell-cell adhesion.

PMID- 20801876
TI  - Collapsin response mediator protein-2 (Crmp2) regulates trafficking by linking
      endocytic regulatory proteins to dynein motors.
AB  - Endocytosis is a conserved cellular process in which nutrients, lipids, and
      receptors are internalized and transported to early endosomes, where they are
      sorted and either channeled to degradative pathways or recycled to the plasma
      membrane. MICAL-L1 and EHD1 are important regulatory proteins that control key
      endocytic transport steps. However, the precise mechanisms by which they mediate
      transport, and particularly the mode by which they connect to motor proteins,
      have remained enigmatic. Here we have identified the collapsin response mediator
      protein-2 (Crmp2) as an interaction partner of MICAL-L1 in non-neuronal cells.
      Crmp2 interacts with tubulin dimers and kinesin and negatively regulates dynein
      based transport in neuronal cells, but its expression and function in non
      neuronal cells have remained poorly characterized. Upon Crmp2 depletion, we
      observed dramatic relocalization of internalized transferrin (Tf) from peripheral
      vesicles to the endocytic recycling compartment (ERC), similar to the effect of
      depleting either MICAL-L1 or EHD1. Moreover, Tf relocalization to the ERC could
      be inhibited by interfering with microtubule polymerization, consistent with a
      role for uncoupled motor protein-based transport upon depletion of Crmp2, MICAL
      L1, or EHD1. Finally, transfection of dynamitin, a component of the dynactin
      complex whose overexpression inhibits dynein activity, prevented the
      relocalization of internalized Tf to the ERC upon depletion of Crmp2, MICAL-L1,
      or EHD1. These data provide the first trafficking regulatory role for Crmp2 in
      non-neuronal cells and support a model in which Crmp2 is an important endocytic
      regulatory protein that links MICAL-L1.EHD1-based vesicular transport to dynein
      motors.

PMID- 20801877
TI  - Aberrant overexpression of the Rgl2 Ral small GTPase-specific guanine nucleotide
      exchange factor promotes pancreatic cancer growth through Ral-dependent and Ral
      independent mechanisms.
AB  - Our recent studies established essential and distinct roles for RalA and RalB
      small GTPase activation in K-Ras mutant pancreatic ductal adenocarcinoma (PDAC)
      cell line tumorigencity, invasion, and metastasis. However, the mechanism of Ral
      GTPase activation in PDAC has not been determined. There are four highly related
      mammalian RalGEFs (RalGDS, Rgl1, Rgl2, and Rgl3) that can serve as Ras effectors.
      Whether or not they share distinct or overlapping functions in K-Ras-mediated
      growth transformation has not been explored. We found that plasma membrane
      targeting to mimic persistent Ras activation enhanced the growth-transforming
      activities of RalGEFs. Unexpectedly, transforming activity did not correlate
      directly with total cell steady-state levels of Ral activation. Next, we observed
      elevated Rgl2 expression in PDAC tumor tissue and cell lines. Expression of
      dominant negative Ral, which blocks RalGEF function, as well as interfering RNA
      suppression of Rgl2, reduced PDAC cell line steady-state Ral activity, growth in
      soft agar, and Matrigel invasion. Surprisingly, the effect of Rgl2 on anchorage
      independent growth could not be rescued by constitutively activated RalA,
      suggesting a novel Ral-independent function for Rgl2 in transformation. Finally,
      we determined that Rgl2 and RalB both localized to the leading edge, and this
      localization of RalB was dependent on endogenous Rgl2 expression. In summary, our
      observations support nonredundant roles for RalGEFs in Ras-mediated oncogenesis
      and a key role for Rgl2 in Ral activation and Ral-independent PDAC growth.

PMID- 20801878
TI  - Structural basis of cyclophilin B binding by the calnexin/calreticulin P-domain.
AB  - Little is known about how chaperones in the endoplasmic reticulum are organized
      into complexes to assist in the proper folding of secreted proteins. One notable
      exception is the complex of ERp57 and calnexin that functions as part the
      calnexin cycle to direct disulfide bond formation in N-glycoproteins. Here, we
      report three new complexes composed of the peptidyl prolyl cis-trans-isomerase
      cyclophilin B and any of the lectin chaperones: calnexin, calreticulin, or
      calmegin. The 1.7 A crystal structure of cyclophilin with the proline-rich P
      domain of calmegin reveals that binding is mediated by the same surface that
      binds ERp57. We used NMR titrations and mutagenesis to measure low micromolar
      binding of cyclophilin to all three lectin chaperones and identify essential
      interfacial residues. The immunosuppressant cyclosporin A did not affect complex
      formation, confirming the functional independence of the P-domain binding and
      proline isomerization sites of cyclophilin. Our results reveal the P-domain
      functions as a unique protein-protein interaction domain and implicate a peptidyl
      prolyl isomerase as a new element in the calnexin cycle.

PMID- 20801879
TI  - Mitotic phosphorylation of Cdc25B Ser321 disrupts 14-3-3 binding to the high
      affinity Ser323 site.
AB  - Cdc25B is a key regulator of entry into mitosis, and its activity and
      localization are regulated by binding of the 14-3-3 dimer. There are three 14-3-3
      binding sites on Cdc25B, with Ser(323) being the highest affinity binding and is
      highly homologous to the Ser(216) 14-3-3 binding site on Cdc25C. Loss of 14-3-3
      binding to Ser(323) increases cyclin/Cdk substrate access to the catalytic site,
      thereby increasing its activity. It also affects the localization of Cdc25B.
      Thus, phosphorylation and 14-3-3 binding to this site is essential for down
      regulating Cdc25B activity, blocking its mitosis promoting function. The question
      of how this inhibitory signal is relieved to allow Cdc25B activation and entry
      into mitosis is yet to be resolved. Here, we show that Ser(323) phosphorylation
      is maintained into mitosis, but phosphorylation of Ser(321) disrupts 14-3-3
      binding to Ser(323), mimicking the effect of inhibiting Ser(323) phosphorylation
      on both Cdc25B activity and localization. The unphosphorylated Ser(321) appears
      to have a role in stabilizing 14-3-3 binding to Ser(323), and loss of the Ser
      hydroxyl group appears to be sufficient to significantly reduce 14-3-3 binding. A
      consequence of loss of 14-3-3 binding is dephosphorylation of Ser(323). Ser(321)
      is phosphorylated in mitosis by Cdk1. The mitotic phosphorylation of Ser(321)
      acts to maintain full activation of Cdc25B by disrupting 14-3-3 binding to
      Ser(323) and enhancing the dephosphorylation of Ser(323) to block 14-3-3 binding
      to this site.

PMID- 20801880
TI  - Molecular basis of phosphatidyl-myo-inositol mannoside biosynthesis and
      regulation in mycobacteria.
AB  - Phosphatidyl-myo-inositol mannosides (PIMs) are unique glycolipids found in
      abundant quantities in the inner and outer membranes of the cell envelope of all
      Mycobacterium species. They are based on a phosphatidyl-myo-inositol lipid anchor
      carrying one to six mannose residues and up to four acyl chains. PIMs are
      considered not only essential structural components of the cell envelope but also
      the structural basis of the lipoglycans (lipomannan and lipoarabinomannan), all
      important molecules implicated in host-pathogen interactions in the course of
      tuberculosis and leprosy. Although the chemical structure of PIMs is now well
      established, knowledge of the enzymes and sequential events leading to their
      biosynthesis and regulation is still incomplete. Recent advances in the
      identification of key proteins involved in PIM biogenesis and the determination
      of the three-dimensional structures of the essential phosphatidyl-myo-inositol
      mannosyltransferase PimA and the lipoprotein LpqW have led to important insights
      into the molecular basis of this pathway.

PMID- 20801881
TI  - An exceptionally potent inducer of cytoprotective enzymes: elucidation of the
      structural features that determine inducer potency and reactivity with Keap1.
AB  - The Keap1/Nrf2/ARE pathway controls a network of cytoprotective genes that defend
      against the damaging effects of oxidative and electrophilic stress, and
      inflammation. Induction of this pathway is a highly effective strategy in
      combating the risk of cancer and chronic degenerative diseases, including
      atherosclerosis and neurodegeneration. An acetylenic tricyclic bis(cyano enone)
      bearing two highly electrophilic Michael acceptors is an extremely potent inducer
      in cells and in vivo. We demonstrate spectroscopically that both cyano enone
      functions of the tricyclic molecule react with cysteine residues of Keap1 and
      activate transcription of cytoprotective genes. Novel monocyclic cyano enones,
      representing fragments of rings A and C of the tricyclic compound, reveal that
      the contribution to inducer potency of the ring C Michael acceptor is much
      greater than that of ring A, and that potency is further enhanced by spatial
      proximity of an acetylenic function. Critically, the simultaneous presence of two
      cyano enone functions in rings A and C within a rigid three-ring system results
      in exceptionally high inducer potency. Detailed understanding of the structural
      elements that contribute to the reactivity with the protein sensor Keap1 and to
      high potency of induction is essential for the development of specific and
      selective lead compounds as clinically relevant chemoprotective agents.

PMID- 20801882
TI  - Requirement of the epithelium-specific Ets transcription factor Spdef for mucous
      gland cell function in the gastric antrum.
AB  - Mucus-secreting cells of the stomach epithelium provide a protective barrier
      against damage that might result from bacterial colonization or other stimuli.
      Impaired barrier function contributes to chronic inflammation and cancer. Knock
      out mice for the epithelium-specific transcription factor Spdef (also called
      Pdef) have defects in terminal differentiation of intestinal and bronchial
      secretory cells. We sought to determine the physiologic function of Spdef in the
      stomach, another site of significant levels of Spdef expression. We used in situ
      hybridization and immunohistochemistry to localize Spdef-expressing cells in the
      mouse stomach; targeted gene disruption to generate mice lacking Spdef; and
      histologic, immunologic, and transcriptional profiling approaches to determine
      the requirements of Spdef in stomach epithelial homeostasis. In wild-type mice,
      Spdef RNA and protein are expressed predominantly in mucous gland cells of the
      antrum and in mucous neck cells of the glandular corpus. Within 1.5 years, nearly
      half of homozygous mutant mice developed profound mucosal hyperplasia of the
      gastric antrum. Submucosal infiltration of inflammatory cells preceded antral
      hyperplasia by several weeks. The absence of Spdef impaired terminal maturation
      of antral mucous gland cells, as reflected in reduced expression of Muc6 and Tff2
      and reduced numbers of secretory granules. Antral gene expression abnormalities
      overlapped significantly with those in Spdef(-/-) colon, including genes
      implicated in secretory granule traffic and functions. Spdef is required for
      terminal maturation of antral mucous gland cells to protect animals from gastric
      inflammation and resulting hyperplasia. These requirements parallel Spdef
      functions in secretory intestinal cells and suggest a common molecular mechanism
      for maturation of gastrointestinal secretory lineages.

PMID- 20801883
TI  - Na+/H+ exchanger regulatory factor-1 is involved in chemokine receptor homodimer
      CCR5 internalization and signal transduction but does not affect CXCR4 homodimer
      or CXCR4-CCR5 heterodimer.
AB  - Chemokine receptors are members of the G protein-coupled receptor (GPCR) family.
      CCR5 is also the principal co-receptor for macrophage-tropic strains of human
      immunodeficiency virus, type 1 (HIV-1), and efforts have been made to develop
      ligands to inhibit HIV-1 infection by promoting CCR5 receptor endocytosis. Given
      the nature of GPCRs and their propensity to form oligomers, one can consider
      ligand-based therapies as unselective in terms of the oligomeric composition of
      complexes. For example, a ligand targeting a CCR5 homomer could likely induce
      signal transduction on a heteromeric CCR5-CXCR4. Other avenues could therefore be
      explored. We identified a receptor adaptor interacting specifically with one
      receptor complex but not others. NHERF1, an adaptor known for its role in
      desensitization, internalization, and regulation of the ERK signaling cascade for
      several GPCRs, interacts via its PDZ2 domain with the CCR5 homodimer but not with
      the CXCR4-CCR5 heterodimer or CXCR4 homodimer. To further characterize this
      interaction, we also show that NHERF1 increases the CCR5 recruitment of arrestin2
      following stimulation. NHERF1 is also involved in CCR5 internalization, as we
      demonstrate that co-expression of constructs bearing the PDZ2 domain can block
      CCR5 internalization. We also show that NHERF1 potentiates RANTES (regulated on
      activation normal T cell expressed and secreted)-induced ERK1/2 phosphorylation
      via CCR5 activation and that this activation requires NHERF1 but not arrestin2.
      Taken together, our results suggest that oligomeric receptor complexes can
      associate specifically with partners and that in this case NHERF1 could represent
      an interesting new target for the regulation of CCR5 internalization and
      potentially HIV infection.

PMID- 20801884
TI  - 3-Deoxy-D-manno-octulosonic acid (Kdo) hydrolase identified in Francisella
      tularensis, Helicobacter pylori, and Legionella pneumophila.
AB  - 3-Deoxy-D-manno-octulosonic acid (Kdo) is an eight-carbon sugar ubiquitous in
      Gram-negative bacterial lipopolysaccharides (LPS). Although its biosynthesis is
      well described, no protein has yet been identified as a Kdo hydrolase. However,
      Kdo hydrolase enzymatic activity has been detected in membranes of Helicobacter
      pylori and Francisella tularensis and may be responsible for the removal of side
      chain Kdo from the LPS core saccharides. We now report the identification of
      genes encoding a Kdo hydrolase in F. tularensis Schu S4 and live vaccine strain
      strains, in H. pylori 26695 strain and in Legionella pneumophila Philadelphia 1
      strain. We have renamed the genes kdhA for keto-deoxyoctulosonate hydrolase A.
      Deletion of kdhA abolished Kdo hydrolase activity in membranes of F. tularensis
      live vaccine strain. The F. tularensis kdhA mutant synthesized a core
      oligosaccharide containing a Kdo disaccharide with one of the Kdo residues being
      a terminal side chain. This side-chain Kdo monosaccharide was absent in the wild
      type core oligosaccharide. Expression in Escherichia coli of recombinant KdhA
      from F. tularensis, H. pylori, and L. pneumophila resulted in a reduction of
      membrane-associated side-chain Kdo. The identification of this previously
      faceless enzyme will accelerate study of the biosynthetic basis and biologic
      impact for postbiosynthetic LPS structural modification.

PMID- 20801885
TI  - Association with {beta}-COP regulates the trafficking of the newly synthesized
      Na,K-ATPase.
AB  - Plasma membrane expression of the Na,K-ATPase requires assembly of its alpha- and
      beta-subunits. Using a novel labeling technique to identify Na,K-ATPase partner
      proteins, we detected an interaction between the Na,K-ATPase alpha-subunit and
      the coat protein, beta-COP, a component of the COP-I complex. When expressed in
      the absence of the Na,K-ATPase beta-subunit, the Na,K-ATPase alpha-subunit
      interacts with beta-COP, is retained in the endoplasmic reticulum, and is
      targeted for degradation. In the presence of the Na,K-ATPase beta-subunit, the
      alpha-subunit does not interact with beta-COP and traffics to the plasma
      membrane. Pulse-chase experiments demonstrate that in cells expressing both the
      Na,K-ATPase alpha- and beta-subunits, newly synthesized alpha-subunit associates
      with beta-COP immediately after its synthesis but that this interaction does not
      constitute an obligate intermediate in the assembly of the alpha- and beta
      subunits to form the pump holoenzyme. The interaction with beta-COP was reduced
      by mutating a dibasic motif at Lys(54) in the Na,K-ATPase alpha-subunit. This
      mutant alpha-subunit is not retained in the endoplasmic reticulum and reaches the
      plasma membrane, even in the absence of Na,K-ATPase beta-subunit expression.
      Although the Lys(54) alpha-subunit reaches the cell surface without need for beta
      subunit assembly, it is only functional as an ion-transporting ATPase in the
      presence of the beta-subunit.

PMID- 20801886
TI  - Nesprin-2 interacts with {alpha}-catenin and regulates Wnt signaling at the
      nuclear envelope.
AB  - Nesprins and emerin are structural nuclear envelope proteins that tether nuclei
      to the cytoskeleton. In this work, we identified the cytoskeleton-associated
      alpha-N/E-catenins as novel nesprin-2-binding partners. The association involves
      the C termini of nesprin-2 giant and alpha-N/E-catenins. alpha-E/T/N-catenins are
      known primarily for their roles in cadherin-mediated cell-cell adhesion. Here, we
      show that, in addition, alpha-catenin forms complexes with nesprin-2 that include
      beta-catenin and emerin. We demonstrate that the depletion of nesprin-2 reduces
      both the amount of active beta-catenin inside the nucleus and T-cell
      factor/lymphoid-enhancing factor-dependent transcription. Taken together, these
      findings suggest novel nesprin-2 functions in cellular signaling. Moreover, we
      propose that, in contrast to emerin, nesprin-2 is a positive regulator of the Wnt
      signaling pathway.

PMID- 20801887
TI  - Vesicle fusion probability is determined by the specific interactions of munc18.
AB  - Mammalian-regulated secretion is absolutely dependent on four evolutionarily
      conserved proteins: three SNARE proteins and munc18. Dissecting the functional
      outcomes of the spatially organized protein interactions between these factors
      has been difficult because of the close interrelationship between different
      binding modes. Here, we investigated the spatial distribution of single munc18
      molecules at the plasma membrane of cells and the underlying interactions between
      syntaxin and munc18. Disruption of munc18 binding to the N-terminal peptide motif
      of syntaxin did not alter munc18 localization on the plasma membrane but had a
      pronounced influence on the behavior of secretory vesicles and their likelihood
      to undergo fusion. We therefore conclude that interaction with the syntaxin N
      peptide can confer differential release probabilities to secretory vesicles and
      may contribute to the delineation of secretory vesicle pools.

PMID- 20801888
TI  - Proteins at work: a combined small angle X-RAY scattering and theoretical
      determination of the multiple structures involved on the protein kinase
      functional landscape.
AB  - C-terminal Src kinase (Csk) phosphorylates and down-regulates the Src family
      tyrosine kinases (SFKs). Crystallographic studies of Csk found an unusual
      arrangement of the SH2 and SH3 regulatory domains about the kinase core, forming
      a compact structure. However, recent structural studies of mutant Csk in the
      presence of an inhibitor indicate that the enzyme accesses an expanded structure.
      To investigate whether wt-Csk may also access open conformations we applied small
      angle x-ray scattering (SAXS). We find wt-Csk frequently occupies an extended
      conformation where the regulatory domains are removed from the kinase core. In
      addition, all-atom structure-based simulations indicate Csk occupies two free
      energy basins. These basins correspond to ensembles of distinct global
      conformations of Csk: a compact structure and an extended structure. The
      transitions between these structures are entropically driven and accessible via
      thermal fluctuations that break local interactions. We further characterized the
      ensemble by generating theoretical scattering curves for mixed populations of
      conformations from both basins and compared the predicted scattering curves to
      the experimental profile. This population-combination analysis is more consistent
      with the experimental data than any rigid model. It suggests that Csk adopts a
      broad ensemble of conformations in solution, populating extended conformations
      not observed in the crystal structure that may play an important role in the
      regulation of Csk. The methodology developed here is broadly applicable to
      biological macromolecules and will provide useful information about what
      ensembles of conformations are consistent with the experimental data as well as
      the ubiquitous dynamic reversible assembly processes inherent in biology.

PMID- 20801889
TI  - Selective fusion of azurophilic granules with Leishmania-containing phagosomes in
      human neutrophils.
AB  - Leishmania parasites use polymorphonuclear neutrophils as intermediate hosts
      before their ultimate delivery to macrophages following engulfment of parasite
      infected neutrophils. This leads to a silent and unrecognized entry of Leishmania
      into the macrophage host cell. Neutrophil function depends on its cytoplasmic
      granules, but their mobilization and role in how Leishmania parasites evade
      intracellular killing in neutrophils remain undetermined. Here, we have found by
      ultrastructural approaches that neutrophils ingested Leishmania major
      promastigotes, and azurophilic granules fused in a preferential way with parasite
      containing phagosomes, without promoting parasite killing. Azurophilic granules,
      identified by the granule marker myeloperoxidase, also fused with Leishmania
      donovani-engulfed vacuoles in human neutrophils. In addition, the azurophilic
      membrane marker CD63 was also detected in the vacuole surrounding the parasite,
      and in the fusion of azurophilic granules with the parasite-engulfed phagosome.
      Tertiary and specific granules, involved in vacuole acidification and superoxide
      anion generation, hardly fused with Leishmania-containing phagosomes. L. major
      interaction with neutrophils did not elicit production of reactive oxygen species
      or mobilization of tertiary and specific granules. By using immunogold electron
      microscopy approaches in the engulfment of L. major and L. donovani by human
      neutrophils, we did not find a significant contribution of endoplasmic reticulum
      to the formation of Leishmania-containing vacuoles. Live Leishmania parasites
      were required to be optimally internalized by neutrophils. Our data suggest that
      Leishmania promastigotes modulate their uptake by neutrophils, and regulate
      granule fusion processes in a rather selective way to favor parasite survival in
      human neutrophils.

PMID- 20801890
TI  - Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977.
AB  - A phosphoramidate prodrug of 2'-deoxy-2'-alpha-fluoro-beta-C-methyluridine-5'
      monophosphate, PSI-7851, demonstrates potent anti-hepatitis C virus (HCV)
      activity both in vitro and in vivo. PSI-7851 is a mixture of two
      diastereoisomers, PSI-7976 and PSI-7977, with PSI-7977 being the more active
      inhibitor of HCV RNA replication in the HCV replicon assay. To inhibit the HCV
      NS5B RNA-dependent RNA polymerase, PSI-7851 must be metabolized to the active
      triphosphate form. The first step, hydrolysis of the carboxyl ester by human
      cathepsin A (CatA) and/or carboxylesterase 1 (CES1), is a stereospecific
      reaction. Western blot analysis showed that CatA and CES1 are both expressed in
      primary human hepatocytes. However, expression of CES1 is undetectable in clone A
      replicon cells. Studies with inhibitors of CatA and/or CES1 indicated that CatA
      is primarily responsible for hydrolysis of the carboxyl ester in clone A cells,
      although in primary human hepatocytes, both CatA and CES1 contribute to the
      hydrolysis. Hydrolysis of the ester is followed by a putative nucleophilic attack
      on the phosphorus by the carboxyl group resulting in the spontaneous elimination
      of phenol and the production of an alaninyl phosphate metabolite, PSI-352707,
      which is common to both isomers. The removal of the amino acid moiety of PSI
      352707 is catalyzed by histidine triad nucleotide-binding protein 1 (Hint1) to
      give the 5'-monophosphate form, PSI-7411. siRNA-mediated Hint1 knockdown studies
      further indicate that Hint1 is, at least in part, responsible for converting PSI
      352707 to PSI-7411. PSI-7411 is then consecutively phosphorylated to the
      diphosphate, PSI-7410, and to the active triphosphate metabolite, PSI-7409, by
      UMP-CMP kinase and nucleoside diphosphate kinase, respectively.

PMID- 20801891
TI  - Resveratrol impairs the release of steroid-resistant inflammatory cytokines from
      human airway smooth muscle cells in chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) therapy is complicated by
      corticosteroid resistance of the interleukin 8 (IL-8)-dependent and granulocyte
      macrophage-colony stimulating factor (GM-CSF)-dependent chronic airway
      inflammation, for whose establishment human airway smooth muscle cells (HASMCs)
      might be crucial. It is unclear whether the release of inflammatory mediators
      from HASMCs is modulated by cigarette smoking and is refractory to
      corticosteroids in COPD. Resveratrol, an antiaging drug with protective effects
      against lung cancer, might be an alternative to corticosteroids in COPD therapy.
      Vascular endothelial growth factor (VEGF) might offer protection from developing
      emphysema. We tested the following hypotheses for HASMCs: 1) smoking with or
      without airway obstruction modulates IL-8, GM-CSF, and VEGF release; and 2)
      corticosteroids, but not resveratrol, fail to inhibit cytokine release in COPD.
      Cytokine release from HASMCs exposed to tumor necrosis factor alpha (TNFalpha),
      dexamethasone, and/or resveratrol was measured via enzyme-linked immunosorbent
      assay and compared between nonsmokers (NS), smokers without COPD (S), and smokers
      with COPD (all n = 10). In response to TNFalpha, IL-8 release was increased, but
      GM-CSF and VEGF release was decreased in S and COPD compared with NS.
      Dexamethasone and resveratrol inhibited concentration-dependently TNFalpha
      induced IL-8, GM-CSF, and VEGF release. For IL-8 and GM-CSF efficiency of
      dexamethasone was NS > S > COPD. That of resveratrol was NS = S = COPD for IL-8
      and NS = S < COPD for GM-CSF. For VEGF the efficiency of dexamethasone was NS = S
      = COPD, and that of resveratrol was NS = S > COPD. All resveratrol effects were
      partially based on p38 mitogen-activated protein kinase blockade. In conclusion,
      smoking modulates cytokine release from HASMCs. Corticosteroid refractoriness of
      HASMCs in COPD is cytokine-dependent. Resveratrol might be superior to
      corticosteroids in COPD therapy, because it more efficiently reduces the release
      of inflammatory mediators and has limited effects on VEGF in COPD.

PMID- 20801892
TI  - Selectively engaging beta-arrestins at the angiotensin II type 1 receptor reduces
      blood pressure and increases cardiac performance.
AB  - Biased G protein-coupled receptor ligands engage subsets of the receptor signals
      normally stimulated by unbiased agonists. However, it is unclear whether ligand
      bias can elicit differentiated pharmacology in vivo. Here, we describe the
      discovery of a potent, selective beta-arrestin biased ligand of the angiotensin
      II type 1 receptor. TRV120027 (Sar-Arg-Val-Tyr-Ile-His-Pro-D-Ala-OH)
      competitively antagonizes angiotensin II-stimulated G protein signaling, but
      stimulates beta-arrestin recruitment and activates several kinase pathways,
      including p42/44 mitogen-activated protein kinase, Src, and endothelial nitric
      oxide synthase phosphorylation via beta-arrestin coupling. Consistent with beta
      arrestin efficacy, and unlike unbiased antagonists, TRV120027 increased
      cardiomyocyte contractility in vitro. In rats, TRV120027 reduced mean arterial
      pressure, as did the unbiased antagonists losartan and telmisartan. However,
      unlike the unbiased antagonists, which decreased cardiac performance, TRV120027
      increased cardiac performance and preserved cardiac stroke volume. These striking
      differences in vivo between unbiased and beta-arrestin biased ligands validate
      the use of biased ligands to selectively target specific receptor functions in
      drug discovery.

PMID- 20801894
TI  - Dietary protein deprivation upregulates insulin signaling and inhibits
      gluconeogenesis in rat liver.
AB  - This study was undertaken to elucidate the effects of dietary protein deprivation
      on glucose metabolism and hepatic insulin signaling in rats. The results of
      glucose and pyruvate tolerance tests in rats fed with a 12% casein diet (12C) and
      a protein-free diet (PF) indicated that protein deprivation enhanced clearance of
      blood glucose and suppressed gluconeogenesis. Correspondingly, the mRNA level of
      hepatic phosphoenolpyruvate carboxykinase, a key gluconeogenic enzyme, was
      suppressed by dietary protein deprivation. In PF-fed rats, total tyrosine
      phosphorylation of insulin receptor (IR) in the liver induced by insulin
      injection was enhanced compared with 12C pair-fed rats due to an increase in IR
      protein level. In addition, protein deprivation caused an increase in protein
      levels of IR substrate 1 (IRS1) and IRS2, leading to the marked enhancement of
      insulin-induced tyrosine phosphorylation of IRS2 and its binding to the p85
      regulatory subunit of phosphatidylinositol 3-kinase (PI3K). Based on these
      results, we conclude that protein deprivation suppresses gluconeogenesis by a
      mechanism primarily mediated by the enhancement of the insulin signals through
      the IR/IRS/PI3K/mammalian target of rapamycin complex 1 pathway in the liver.
      Taken together with our previous report, these findings suggest that tissue
      specific potentiation of insulin action in the liver and the skeletal muscle
      plays important roles in maintaining glucose homeostasis even when energy usage
      is reduced by dietary protein deprivation.

PMID- 20801893
TI  - In vitro cytotoxicity and in vivo efficacy, pharmacokinetics, and metabolism of
      10074-G5, a novel small-molecule inhibitor of c-Myc/Max dimerization.
AB  - The c-Myc oncoprotein is overexpressed in many tumors and is essential for
      maintaining the proliferation of transformed cells. To function as a
      transcription factor, c-Myc must dimerize with Max via the basic helix-loop-helix
      leucine zipper protein (bHLH-ZIP) domains in each protein. The small molecule 7
      nitro-N-(2-phenylphenyl)-2,1,3-benzoxadiazol-4-amine (10074-G5) binds to and
      distorts the bHLH-ZIP domain of c-Myc, thereby inhibiting c-Myc/Max heterodimer
      formation and inhibiting its transcriptional activity. We report in vitro
      cytotoxicity and in vivo efficacy, pharmacodynamics, pharmacokinetics, and
      metabolism of 10074-G5 in human xenograft-bearing mice. In vitro, 10074-G5
      inhibited the growth of Daudi Burkitt's lymphoma cells and disrupted c-Myc/Max
      dimerization. 10074-G5 had no effect on the growth of Daudi xenografts in C.B-17
      SCID mice that were treated with 20 mg/kg 10074-G5 intravenously for 5
      consecutive days. Inhibition of c-Myc/Max dimerization in Daudi xenografts was
      not seen 2 or 24 h after treatment. Concentrations of 10074-G5 in various
      matrices were determined by high-performance liquid chromatography-UV, and
      metabolites of 10074-G5 were identified by liquid chromatography/tandem mass
      spectrometry. The plasma half-life of 10074-G5 in mice treated with 20 mg/kg i.v.
      was 37 min, and peak plasma concentration was 58 MUM, which was 10-fold higher
      than peak tumor concentration. The lack of antitumor activity probably was caused
      by the rapid metabolism of 10074-G5 to inactive metabolites, resulting in tumor
      concentrations of 10074-G5 insufficient to inhibit c-Myc/Max dimerization. Our
      identification of 10074-G5 metabolites in mice will help design new, more
      metabolically stable small-molecule inhibitors of c-Myc.

PMID- 20801895
TI  - A study of somatolactin actions by ectopic expression in transgenic zebrafish
      larvae.
AB  - Somatolactin (SL) is a fish-specific hormone that belongs to the prolactin (PRL)
      and GH family. Recently, two forms of SL, SLalpha and SLbeta, have been found in
      some species, and may have different actions and functions. To investigate the
      role of SL in fish growth and metabolism, we generated transgenic fish founders
      with ectopic expression of SLalpha and SLbeta to study the physiological
      functions and actions of these SLs among several marker genes. We fused the cDNAs
      encoding the precursor SLs in frame to a zebrafish beta-actin gene promoter to
      generate transgenic zebrafish lines that were coinjected with a green fluorescent
      protein (GFP) driven by the same promoter. The transgenic zebrafish were selected
      based on GFP expression and confirmed by genomic PCR, Southern blot analysis, and
      transgene expression. Investigations into the expression of marker genes in
      larvae on different pathways using real-time PCR have provided a general
      understanding of the actions of SLs. This study found that the overexpression of
      SLalpha and SLbeta in vivo significantly enhanced the transcription of IGFs,
      insulin, leptin, sterol regulatory element binding protein 1, and fatty acid
      synthase, as well as the expression level of vitellogenin and
      proopiomelanocortin, while causing reduced levels of catalase and glutathione S
      transferase in the larvae of transgenic zebrafish.

PMID- 20801896
TI  - Individual differences in prefrontal cortex activity during perception of bitter
      taste using fNIRS methodology.
AB  - Although bitter taste has a crucial role in nutrition by preventing the ingestion
      of toxic foods, there are few studies on bitter taste neuroimaging. To identify
      cortical areas involved in bitter taste perception and to determine if individual
      differences in taste sensitivity to 6-n-propylthiouracil (PROP) are represented
      in the brain by different cortical activation patterns, we examined 48 healthy
      volunteers using functional near-infrared spectroscopy. Participants rated the
      perceived intensity of filter paper disks impregnated with PROP and NaCl during
      the imaging procedure and were then classified as PROP tasters and nontasters. We
      monitored cortical activity in both the anterior and posterior regions of the
      dorsolateral prefrontal cortex (DLPFC) and in the ventrolateral prefrontal cortex
      (VLPFC). No activity was detected in the anterior DLPFC in any of the
      participants. However, during the administration of PROP, significant cortical
      activation was detected in the more posterior regions of the left DLPFC and in
      the left and right VLPFC but only in PROP tasters. PROP nontasters showed no
      cortical activity in these areas. These data suggest that the prefrontal cortex
      is involved in the conscious perception of the bitter taste of PROP and that the
      pattern of activity is consistent with individual differences in the ability to
      taste this compound. Thus, the PROP phenotype is associated with fundamental
      differences in cortical taste processing.

PMID- 20801897
TI  - The role of the contralesional motor cortex for motor recovery in the early days
      after stroke assessed with longitudinal FMRI.
AB  - Stroke may trigger a number of cellular and molecular events in perilesional and
      remote brain regions enabling cortical reorganization and recovery of function.
      We here investigated the pattern and time course of acute stroke-induced changes
      in motor system activity during motor recovery using functional magnetic
      resonance imaging. Hand movement-related neural activity was assessed in 11 acute
      stroke patients scanned 3 times during the first 2 weeks starting within 72 h
      after symptom onset. A motor recovery score was computed based on the action
      research arm test and the maximum grip force. Increases of activity in primary
      motor cortex, premotor cortex (dorsal and ventral), and supplementary motor area
      in both hemispheres significantly correlated with behavioral recovery. These
      longitudinal changes depended upon the degree of initial motor impairment:
      Patients with mild deficits did not differ from healthy subjects. In contrast,
      patients with severe deficits were characterized by a global reduction of task
      related activity, followed by increases in ipsilesional as well as contralesional
      motor areas. The finding that the gradually increasing activity in contralesional
      primary motor and premotor cortex correlated with improved functional recovery in
      severely affected patients indicates early cortical reorganization supporting
      motor function of the affected hand.

PMID- 20801898
TI  - Distinct gene expression profiles in subsets of chronic lymphocytic leukemia
      expressing stereotyped IGHV4-34 B-cell receptors.
AB  - BACKGROUND: Numerous subsets of patients with chronic lymphocytic leukemia
      display similar immunoglobulin gene usage with almost identical complementarity
      determining region 3 sequences. Among IGHV4-34 cases, two such subsets with
      "stereotyped" B-cell receptors were recently identified, i.e. subset #4 (IGHV4
      34/IGKV2-30) and subset #16 (IGHV4-34/IGKV3-20). Subset #4 patients appear to
      share biological and clinical features, e.g. young age at diagnosis and indolent
      disease, whereas little is known about subset #16 at a clinical level. DESIGN AND
      METHODS: We investigated the global gene expression pattern in sorted chronic
      lymphocytic leukemia cells from 25 subset/non-subset IGHV4-34 patients using
      Affymetrix gene expression arrays. RESULTS: Although generally few differences
      were found when comparing subset to non-subset 4/16 IGHV4-34 cases, distinct gene
      expression profiles were revealed for subset #4 versus subset #16. The
      differentially expressed genes, predominantly with lower expression in subset #4
      patients, are involved in important cell regulatory pathways including cell-cycle
      control, proliferation and immune response, which may partly explain the low
      proliferative disease observed in subset #4 patients. CONCLUSIONS: Our novel data
      demonstrate distinct gene expression profiles among patients with stereotyped
      IGHV4-34 B-cell receptors, providing further evidence for biological differences
      in the pathogenesis of these subsets and underscoring the functional relevance of
      subset assignment based on B-cell receptor sequence features.

PMID- 20801899
TI  - Mesenchymal stromal cells transiently alter the inflammatory milieu post
      transplant to delay graft-versus-host disease.
AB  - BACKGROUND: Multipotent mesenchymal stromal cells suppress T-cell function in
      vitro, a property that has underpinned their use in treating clinical steroid
      refractory graft-versus-host disease after allogeneic hematopoietic stem cell
      transplantation. However the potential of mesenchymal stromal cells to resolve
      graft-versus-host disease is confounded by a paucity of pre-clinical data
      delineating their immunomodulatory effects in vivo. DESIGN AND METHODS: We
      examined the influence of timing and dose of donor-derived mesenchymal stromal
      cells on the kinetics of graft-versus-host disease in two murine models of graft
      versus-host disease (major histocompatibility complex-mismatched: UBI-GFP/BL6 [H
      2(b)]->BALB/c [H-2(d)] and the sibling transplant mimic, UBI-GFP/BL6 [H-2(b)]
      >BALB.B [H-2(b)]) using clinically relevant conditioning regimens. We also
      examined the effect of mesenchymal stromal cell infusion on bone marrow and
      spleen cellular composition and cytokine secretion in transplant recipients.
      RESULTS: Despite T-cell suppression in vitro, mesenchymal stromal cells delayed
      but did not prevent graft-versus-host disease in the major histocompatibility
      complex-mismatched model. In the sibling transplant model, however, 30% of
      mesenchymal stromal cell-treated mice did not develop graft-versus-host disease.
      The timing of administration and dose of the mesenchymal stromal cells influenced
      their effectiveness in attenuating graft-versus-host disease, such that a low
      dose of mesenchymal stromal cells administered early was more effective than a
      high dose of mesenchymal stromal cells given late. Compared to control-treated
      mice, mesenchymal stromal cell-treated mice had significant reductions in serum
      and splenic interferon-gamma, an important mediator of graft-versus-host disease.
      CONCLUSIONS: Mesenchymal stromal cells appear to delay death from graft-versus
      host disease by transiently altering the inflammatory milieu and reducing levels
      of interferon-gamma. Our data suggest that both the timing of infusion and the
      dose of mesenchymal stromal cells likely influence these cells' effectiveness in
      attenuating graft-versus-host disease.

PMID- 20801900
TI  - Highly active antiretroviral therapy alone may be an effective treatment for HIV
      associated multi-centric Castleman's disease.

PMID- 20801901
TI  - Effusion-associated anaplastic large cell lymphoma of the breast: time for it to
      be defined as a distinct clinico-pathological entity.

PMID- 20801902
TI  - Integration of molecular and clinical data of 40 unrelated von Willebrand Disease
      families in a Spanish locus-specific mutation database: first release including
      58 mutations.

PMID- 20801903
TI  - Indoleamine 2,3-dioxygenase-expressing leukemic dendritic cells impair a leukemia
      specific immune response by inducing potent T regulatory cells.
AB  - BACKGROUND: The immunoregulatory enzyme indoleamine 2,3-dioxygenase, which
      catalyzes the conversion of tryptophan into kynurenine, is expressed in a
      significant subset of patients with acute myeloid leukemia, resulting in the
      inhibition of T-cell proliferation and the induction of regulatory T cells. Acute
      myeloid leukemia cells can be differentiated into dendritic cells, which have
      increased immunogenicity and have been proposed as vaccines against leukemia.
      DESIGN AND METHODS: Leukemic dendritic cells were generated from acute myeloid
      leukemia cells and used as stimulators in functional assays, including the
      induction of regulatory T cells. Indoleamine 2,3-dioxygenase expression in
      leukemic dendritic cells was evaluated at molecular, protein and enzymatic
      levels. RESULTS: We demonstrate that, after differentiation into dendritic cells,
      both indoleamine 2,3-dioxygenase-negative and indoleamine 2,3-dioxygenase
      positive acute myeloid leukemia samples show induction and up-regulation of
      indoleamine 2,3-dioxygenase gene and protein, respectively. Indoleamine 2,3
      dioxygenase-positive acute myeloid leukemia dendritic cells catabolize tryptophan
      into kynurenine metabolite and inhibit T-cell proliferation through an
      indoleamine 2,3-dioxygenase-dependent mechanism. Moreover, indoleamine 2,3
      dioxygenase-positive leukemic dendritic cells increase the number of allogeneic
      and autologous CD4(+)CD25(+) Foxp3(+) T cells and this effect is completely
      abrogated by the indoleamine 2,3-dioxygenase-inhibitor, 1-methyl tryptophan.
      Purified CD4(+)CD25(+) T cells obtained from co-culture with indoleamine 2,3
      dioxygenase-positive leukemic dendritic cells act as regulatory T cells as they
      inhibit naive T-cell proliferation and impair the complete maturation of normal
      dendritic cells. Importantly, leukemic dendritic cell-induced regulatory T cells
      are capable of in vitro suppression of a leukemia-specific T cell-mediated immune
      response, directed against the leukemia-associated antigen, Wilms' tumor protein.
      CONCLUSIONS: These data identify indoleamine 2,3-dioxygenase-mediated catabolism
      as a tolerogenic mechanism exerted by leukemic dendritic cells and have clinical
      implications for the use of these cells for active immunotherapy of leukemia.

PMID- 20801904
TI  - Physical activity and risk of venous thromboembolism. The Tromso study.
AB  - BACKGROUND: Previous studies have shown differences in the impact of regular
      physical exercise on the risk of venous thromboembolism. The inconsistent
      findings may have depended on differences in study design and specific population
      cohorts (men only, women only and elderly). We conducted a prospective,
      population-based cohort to investigate the impact of regular physical exercise on
      the risk of venous thromboembolism. DESIGN AND METHODS: Risk factors, including
      self-reported moderate intensity physical exercise during leisure time, were
      recorded for 26,490 people aged 25-97 years old, who participated in a population
      health survey, the Tromso study, in 1994-95. Incident venous thromboembolic
      events were registered during the follow-up until September 1, 2007. RESULTS:
      There were 460 validated incident venous thromboembolic events (1.61 per 1000
      person-years) during a median of 12.5 years of follow-up. Age, body mass index,
      the proportion of daily smokers, total cholesterol, and serum triglycerides
      decreased (P<0.001), whereas high density cholesterol increased (P<0.001) across
      categories of more physical exercise. Regular physical exercise of moderate to
      high intensity during leisure time did not significantly affect the risk of
      venous thromboembolism in the general population. However, compared to
      inactivity, high amounts of physical exercise (>= 3 hours/week) tended to
      increase the risk of provoked venous thromboembolism (multivariable hazard ratio,
      1.30; 95% confidence interval, 0.84-2.0), and total venous thromboembolism in the
      elderly (multivariable hazard ratio, 1.33; 95% confidence interval, 0.80-2.21)
      and in the obese (multivariable hazard ratio, 1.49; 95% confidence interval, 0.63
      3.50). Contrariwise, compared to inactivity, moderate physical activity (1.0-2.9
      hours/week) was associated with a border-line significant decreased risk of
      venous thromboembolism among subjects under 60 years old (multivariable hazard
      ratio, 0.72; 95% confidence interval, 0.48-1.08) and subjects with a body mass
      index of less than 25 kg/m(2) (multivariable hazard ratio, 0.59; 95% confidence
      interval, 0.35-1.01). CONCLUSIONS: Our study showed that regular, moderate
      intensity physical exercise did not have a significant impact on the risk of
      venous thromboembolism in a general population. Future studies are required to
      assess the impact of regular physical exercise on venous thromboembolism risk in
      different population subgroups.

PMID- 20801905
TI  - ERCC1 influence on the incidence of brain metastases in patients with non
      squamous NSCLC treated with adjuvant cisplatin-based chemotherapy.
AB  - BACKGROUND: We recently demonstrated that excision repair cross-complementing
      group 1 protein (ERCC1) is predictive of adjuvant cisplatin-based chemotherapy
      benefit in resected non-small-cell lung cancer (NSCLC). Non-squamous cell
      carcinomas (non-SCCs) carry an increased risk of brain metastases (BMs). We
      hypothesised that there might be an increased incidence of BMs in ERCC1-negative
      non-SCCs when treated with adjuvant cisplatin-based chemotherapy. PATIENTS AND
      METHODS: Incidence of BMs and histoclinical parameters were analysed in a
      population of 761 patients enrolled in the International Adjuvant Lung Cancer
      Trial. A subgroup analysis was carried out in patients with ERCC1-negative non
      SCCs. RESULTS: Of 761 patients, 98 developed BMs alone or in association with
      other metastatic sites, with a 5-year incidence rate of 18.0% (14.7%-21.8%). In
      the multivariate analysis, the clinical parameters associated with the occurrence
      of BMs were the nodal status (P = 0.02) and histological type [give hazard ratio
      (HR) for non-squamous to quantify introduction assertion, P = 0.002].
      Chemotherapy had no effect on BMs [HR = 1.4 (0.90-2.1), P = 0.14]. In patients
      with non-SCC histology (n = 335), adjuvant chemotherapy was associated with an
      increased risk of BMs [HR = 2.1 (1.01-4.3), P = 0.04] for ERCC1-negative tumours,
      whereas there was no evidence of an effect on BMs for ERCC1-positive tumours [HR
      = 1.1 (0.38-3.0), P = 0.90]. Nevertheless, these two effects are not different (P
      = 0.30 for interaction) possibly due to a lack of power in this subgroup.
      CONCLUSIONS: This study suggests that adjuvant cisplatin-based chemotherapy is
      associated with an increased risk of BMs in patients with resected chemosensitive
      non-SCCs. If confirmed, these data could provide a rationale for new follow-up
      and/or prophylactic strategies.

PMID- 20801907
TI  - Choosing among partition models in Bayesian phylogenetics.
AB  - Bayesian phylogenetic analyses often depend on Bayes factors (BFs) to determine
      the optimal way to partition the data. The marginal likelihoods used to compute
      BFs, in turn, are most commonly estimated using the harmonic mean (HM) method,
      which has been shown to be inaccurate. We describe a new more accurate method for
      estimating the marginal likelihood of a model and compare it with the HM method
      on both simulated and empirical data. The new method generalizes our previously
      described stepping-stone (SS) approach by making use of a reference distribution
      parameterized using samples from the posterior distribution. This avoids one
      challenging aspect of the original SS method, namely the need to sample from
      distributions that are close (in the Kullback-Leibler sense) to the prior. We
      specifically address the choice of partition models and find that using the HM
      method can lead to a strong preference for an overpartitioned model. In contrast
      to the HM method and the original SS method, we show using simulated data that
      the generalized SS method is strikingly more precise (repeatable BF values of the
      same data and partition model) and yields BF values that are much more reasonable
      than those produced by the HM method. Comparisons of HM and generalized SS
      methods on an empirical data set demonstrate that the generalized SS method tends
      to choose simpler partition schemes that are more in line with expectation based
      on inferred patterns of molecular evolution. The generalized SS method shares
      with thermodynamic integration the need to sample from a series of distributions
      in addition to the posterior. Such dedicated path-based Markov chain Monte Carlo
      analyses appear to be a cost of estimating marginal likelihoods accurately.

PMID- 20801908
TI  - Combining comparative sequence and genomic data to ascertain phylogenetic
      relationships and explore the evolution of the large GDSL-lipase family in land
      plants.
AB  - The GDSL-lipase gene family is a very large subfamily within the supergene family
      of SGNH esterases, defined by the distinct GDSL amino acid motif and several
      highly conserved domains. Plants retain a large number of GDSL-lipases indicating
      that they have acquired important functions. Yet, in planta functions have been
      demonstrated for only a few GDSL-lipases from diverse species. Considering that
      orthologs often retain equivalent functions, we determined the phylogenetic
      relationships between GDSL-lipases from genome-sequenced species representing
      bryophytes, gymnosperms, monocots, and eudicots. An unrooted phylogenetic tree
      was constructed from the amino acid sequences of 604 GDSL-lipases from seven
      species. The topology of the tree depicts two major and one minor subfamily. This
      division is also supported by the unique gene structure of each subfamily.
      Because GDSL-lipase genes of all species are present in each of the three
      subfamilies, we conclude that the last common ancestor of the land plants already
      possessed at least one ancestral GDSL-lipase gene of each subfamily. Combined
      gene structure and synteny analyses revealed events of segmental duplications,
      gene transposition, and gene degeneration in the evolution of the GDSL-lipase
      gene family. Furthermore, these analyses showed that independent events of intron
      gain and loss also contributed to the extant repertoire of the GDSL-lipase gene
      family. Our findings suggest that underlying many of the intron losses was a
      spliceosomal-mediated mechanism followed by gene conversion. Sorting the
      phylogenetic relationships among the members of the GDSL-lipase gene family, as
      depicted by the tree and supported by synteny analyses, provides a framework for
      extrapolation of demonstrated functional data to GDSL-lipases, whose function is
      yet unknown. Furthermore, function(s) associated with specific lineage(s)
      enriched branches may reveal correlations between acquired and/or lost functions
      and speciation.

PMID- 20801906
TI  - TCDD induced pericardial edema and relative COX-2 expression in medaka (Oryzias
      Latipes) embryos.
AB  - Exposure to dioxin and other aryl hydrocarbon receptor (AhR) ligands results in
      multiple, specific developmental cardiovascular phenotypes including pericardial
      edema and circulatory failure in small aquarium fish models. Although phenotypes
      are well described, mechanistic underpinnings for such toxicities remain elusive.
      Here we suggest that AhR activation results in stimulation of inflammation and
      "eicosanoid" pathways, which contribute to the observed developmental,
      cardiovascular phenotypes. We demonstrate that medaka embryos exposed to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) (0.05-1 ppb) during early development result
      in a dose-related increase in the prevalence of pericardial edema and that this
      phenotype correlates with an increase in cyclooxygenase-2 (COX-2) gene
      expression. Those individuals exhibiting the edema phenotype had significantly
      greater COX-2 mRNA than their nonedematous cohort. Selective pharmacological
      inhibition of COX-2, with NS-398, and genetic knock down of COX-2 with a
      translation initiation morpholino significantly attenuated prevalence and
      severity of edema phenotype. Subsequently, exposures of medaka embryos to
      arachidonic acid (AA) resulted in recapitulation of the pericardial edema
      phenotype and significantly increased COX-2 expression only in those individuals
      exhibiting the edema phenotype compared with their nonedematous cohort. AA
      exposure does not result in significant induction of cytochrome P450 1A
      expression, suggesting that pericardial edema can be induced independent of
      AhR/aryl hydrocarbon receptor nuclear translocator/dioxin response element
      interactions. Results from this study demonstrate that developmental exposure to
      TCDD results in an induction of inflammatory mediators including COX-2, which
      contribute to the onset, and progression of heart dysmorphogenesis in the medaka
      model.

PMID- 20801909
TI  - Decrease in mitochondrial function in rat cardiac permeabilized fibers correlates
      with the aging phenotype.
AB  - We measured the loss of cardiac mitochondrial function related to aging in males
      of three rat strains presenting with different longevity and aging phenotypes:
      the Fischer 344 (F344), the Brown Norway (BN), and the hybrid F344*BN. The F344
      rat has a short life span and a ~45% decrease in coupled mitochondrial oxidation
      in the cardiac permeabilized fibers from the old rats compared with the young
      rats. Citrate synthase activity in the permeabilized fibers (mitochondrial
      content) did not change significantly with aging. The BN live longer compared
      with the F344 and have a 15%-18% loss of mitochondrial respiration in the aged
      rats compared with the young rats. The differences are not significant. In
      hybrids, more resistant to aging than are the BN and the F344, mitochondrial
      function is preserved during aging. The difference in longevity of the different
      strains is correlated with mitochondrial dysfunction in the heart, suggesting the
      importance of mitochondria in cardiac aging.

PMID- 20801910
TI  - A study of the efficiency of pooling in haplotype estimation.
AB  - MOTIVATION: It has been claimed in the literature that pooling DNA samples is
      efficient in estimating haplotype frequencies. There is, however, no theoretical
      justification based on calculation of statistical efficiency. In fact, the
      limited evidence given so far is based on simulation studies with small numbers
      of loci. With rapid advance in technology, it is of interest to see if pooling is
      still efficient when the number of loci increases. METHODS: Instead of resorting
      to simulation studies, we make use of asymptotic statistical theory to perform
      exact calculation of the efficiency of pooling relative to no pooling in the
      estimation of haplotype frequencies. As an intermediate step, we use the log
      linear formulation of the haplotype probabilities and derive the asymptotic
      variance-covariance matrix of the maximum likelihood estimators of the canonical
      parameters of the log-linear model. RESULTS: Based on our calculations under
      linkage equilibrium, pooling can suffer huge loss in efficiency relative to no
      pooling when there are more than three independent loci and the alleles are not
      rare. Pooling works better for rare alleles. In particular, if all the minor
      allele frequencies are 0.05, pooling maintains an advantage over no pooling until
      the number of independent loci reaches 6. High linkage disequilibrium effectively
      reduces the number of independent loci by ruling out certain haplotypes from
      occurring. Similar calculations of efficiency for the case of no pooling justify
      the common belief that it is not worthwhile to use molecular methods to resolve
      the phase ambiguity of individual genotype data. AVAILABILITY: The R codes for
      the calculation are available at http://www.stat.nus.edu.sg/~staxj/pooling
      CONTACT: stakuka@nus.edu.sg.

PMID- 20801911
TI  - miRNAkey: a software for microRNA deep sequencing analysis.
AB  - MOTIVATION: MicroRNAs (miRNAs) are short abundant non-coding RNAs critical for
      many cellular processes. Deep sequencing (next-generation sequencing)
      technologies are being readily used to receive a more accurate depiction of miRNA
      expression profiles in living cells. This type of analysis is a key step towards
      improving our understanding of the complexity and mode of miRNA regulation.
      RESULTS: miRNAkey is a software package designed to be used as a base-station for
      the analysis of miRNA deep sequencing data. The package implements common steps
      taken in the analysis of such data, as well as adds unique features, such as data
      statistics and multiple read determination, generating a novel platform for the
      analysis of miRNA expression. A user-friendly graphical interface is applied to
      determine the analysis steps. The tabular and graphical output contains general
      and detailed reports on the sequence reads and provides an accurate picture of
      the differentially expressed miRNAs in paired samples. AVAILABILITY AND
      IMPLEMENTATION: See http://ibis.tau.ac.il/miRNAkey CONTACT:
      nshomron@post.tau.ac.il SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 20801912
TI  - Ontology- and graph-based similarity assessment in biological networks.
AB  - SUMMARY: A standard systems-based approach to biomarker and drug target discovery
      consists of placing putative biomarkers in the context of a network of biological
      interactions, followed by different 'guilt-by-association' analyses. The latter
      is typically done based on network structural features. Here, an alternative
      analysis approach in which the networks are analyzed on a 'semantic similarity'
      space is reported. Such information is extracted from ontology-based functional
      annotations. We present SimTrek, a Cytoscape plugin for ontology-based similarity
      assessment in biological networks. AVAILABILITY:
      http://rosalind.infj.ulst.ac.uk/SimTrek.html CONTACT: francisco.azuaje@crp
      sante.lu SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 20801913
TI  - Simple sequence-based kernels do not predict protein-protein interactions.
AB  - MOTIVATION: A number of methods have been reported that predict protein-protein
      interactions (PPIs) with high accuracy using only simple sequence-based features
      such as amino acid 3mer content. This is surprising, given that many protein
      interactions have high specificity that depends on detailed atomic recognition
      between physiochemically complementary surfaces. Are the reported high accuracies
      realistic? RESULTS: We find that the reported accuracies of the predictions are
      significantly over-estimated, and strongly dependent on the structure of the
      training and testing datasets used. The choice of which protein pairs are deemed
      as non-interactions in the training data has a variable impact on the accuracy
      estimates, and the accuracies can be artificially inflated by a bias towards
      dominant samples in the positive data which result from the presence of hub
      proteins in the protein interaction network. To address this bias, we propose a
      positive set-specific method to create a 'balanced' negative set maintaining the
      degree distribution for each protein, leading to the conclusion that simple
      sequence-based features contain insufficient information to be useful for
      predicting PPIs, but that protein domain-based features have some predictive
      value. AVAILABILITY: Our method, named 'BRS-nonint', is available at
      http://www.bioinformatics.leeds.ac.uk/BRS-nonint/. All the datasets used in this
      study are derived from publicly available data, and are available at
      http://www.bioinformatics.leeds.ac.uk/BRS-nonint/PPI_RandomBalance.html CONTACT:
      maozuguo@hit.edu.cn; d.r.westhead@leeds.ac.uk.

PMID- 20801914
TI  - DCGL: an R package for identifying differentially coexpressed genes and links
      from gene expression microarray data.
AB  - SUMMARY: Gene coexpression analysis was developed to explore gene interconnection
      at the expression level from a systems perspective, and differential coexpression
      analysis (DCEA), which examines the change in gene expression correlation between
      two conditions, was accordingly designed as a complementary technique to
      traditional differential expression analysis (DEA). Since there is a shortage of
      DCEA tools, we implemented in an R package 'DCGL' five DCEA methods for
      identification of differentially coexpressed genes and differentially coexpressed
      links, including three currently popular methods and two novel algorithms
      described in a companion paper. DCGL can serve as an easy-to-use tool to
      facilitate differential coexpression analyses. CONTACT: yyli@scbit.org and
      yxli@scbit.org SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 20801915
TI  - Activation of the plant mitochondrial potassium channel by free fatty acids and
      acyl-CoA esters: a possible defence mechanism in the response to hyperosmotic
      stress.
AB  - The effect of free fatty acids (FFAs) and acyl-CoA esters on K(+) uptake was
      studied in mitochondria isolated from durum wheat (Triticum durum Desf.), a
      species that has adapted well to the semi-arid Mediterranean area and possessing
      a highly active mitochondrial ATP-sensitive K(+) channel (PmitoK(ATP)), that may
      confer resistance to environmental stresses. This was made by swelling
      experiments in KCl solution under experimental conditions in which PmitoK(ATP)
      activity was monitored. Linoleate and other FFAs (laurate, palmitate, stearate,
      palmitoleate, oleate, arachidonate, and the non-physiological 1
      undecanesulphonate and 5-phenylvalerate), used at a concentration (10 MUM) unable
      to damage membranes of isolated mitochondria, stimulated K(+) uptake by about 2-4
      fold. Acyl-CoAs also promoted K(+) transport to a much larger extent with respect
      to FFAs (about 5-12-fold). In a different experimental system based on safranin O
      fluorescence measurements, the dissipation of electrical membrane potential
      induced by K(+) uptake via PmitoK(ATP) was found to increase in the presence of 5
      phenylvalerate and palmitoyl-CoA, both unable to elicit the activity of the Plant
      Uncoupling Protein. This result suggests a direct activation of PmitoK(ATP).
      Stimulation of K(+) transport by FFAs/acyl-CoAs resulted in a widespread
      phenomenon in plant mitochondria from different mono/dicotyledonous species
      (bread wheat, barley, triticale, maize, lentil, pea, and topinambur) and from
      different organs (root, tuber, leaf, and shoot). Finally, an increase in
      mitochondrial FFAs up to a content of 50 nmol mg(-1) protein, which was able to
      activate PmitoK(ATP) strongly, was observed under hyperosmotic stress conditions.
      Since PmitoK(ATP) may act against environmental/oxidative stress, its activation
      by FFAs/acyl-CoAs is proposed to represent a physiological defence mechanism.

PMID- 20801916
TI  - Residents' practices and perceptions about do not resuscitate orders and
      pronouncing death: an opportunity for clinical training.
AB  - BACKGROUND: Although ''Do not resuscitate'' (DNR) orders are among the most
      commonly discussed patient preference treatment measures, few studies have
      assessed internal medicine residents' views on this complex topic. Our objective
      was to assess resident practices in establishing code status. We also examined
      resident training and experiences in pronouncing death. METHODS: An 18-question
      survey addressing DNR discussions and pronouncing death was emailed to internal
      medicine residents in the state of Illinois. Each question had multiple-choice
      options. RESULTS: A total of 175 residents completed the questionnaire (22%
      response rate). Seventy-eight percent of the residents had discussed DNR status
      with patients or their families at least 9 times. However, only one third of the
      residents felt very comfortable in such discussions. Only 26% of the residents
      had been observed by a faculty member during a code status discussion and fewer
      (16%) while pronouncing death. Do not resuscitate discussions rarely occurred in
      an outpatient clinic (27%). Most residents (90%) thought they would benefit from
      formal training in DNR discussion. CONCLUSION: Although most residents discuss
      DNR status with patients and families, only a quarter are observed in such
      discussions by attending physicians and only a third feel comfortable with this
      aspect of clinical care. Developing a structured residency program curriculum to
      address resident skills in end-of-life care would benefit residency training.

PMID- 20801917
TI  - Methylnaltrexone: treatment for opioid-induced constipation.
AB  - Opioids have become the gold standard for treatment of severe pain in advanced
      disease, but adverse effects can affect the quality of life. Opioid-induced bowel
      dysfunction can lead to refractory constipation. Methylnaltrexone bromide is a
      peripherally acting mu antagonist and is indicated for the treatment of opioid
      induced constipation in patients with advanced illness, when response to standard
      laxative therapy has been inefficacious. This pharmacology update will review the
      etiology, pathophysiology, and treatment of opioid-induced constipation, focused
      on methylnaltrexone as a novel treatment for refractory cases.

PMID- 20801918
TI  - End-of-life experiences: reaching out for compassion, communication, and
      connection-meaning of deathbed visions and coincidences.
AB  - A recent study shows that the greatest fear for many Britons is to die alone.
      More than half the complaints received by the UK National Health Service (NHS)
      concern end-of-life care, with an emphasis on spiritual matters. Much has been
      written on the spiritual needs of the dying, but many doctors and nurses still
      find this a difficult area to approach. They lack the confidence and/or training
      to recognize or discuss spiritual aspects of death and dying or to affirm the
      spiritual needs of the dying person. Our end-of-life experience (ELE) research
      suggests that deathbed visions (DVs) and deathbed coincidences (DCs) are not
      uncommon, and that the dying process appears to involve an instinctive need for
      spiritual connection and meaning, requiring compassionate understanding and
      respect from those who provide end-of-life care.

PMID- 20801919
TI  - The influence of hyperglycemia and other clinical variables on rehabilitation and
      hospital length of stay after neurosurgery in patients with cancer.
AB  - OBJECTIVE: Our study was designed to address whether steroid-induced
      hyperglycemia after neurosurgery affects rehabilitation and hospital length of
      stay (LOS) in patients with cancer. PATIENTS AND METHODS: We reviewed the medical
      records of 290 post-neurosurgery patients at our cancer center in 2002. RESULTS:
      Of the 267 nondiabetic patients and 23 diabetic patients (P < .001), 2 and 8,
      respectively, had hyperglycemia which is defined as casual plasma glucose
      concentrations of >=200 mg/dL on 2 different days. In all patients studied,
      hyperglycemia does not predict longer hospital stay or needs for rehabilitation.
      CONCLUSIONS: The frequency of corticosteroid-induced hyperglycemia in post
      neurosurgery patients with cancer was low.

PMID- 20801920
TI  - Barriers to hospice care in Alabama: provider-based perceptions.
AB  - Few studies have evaluated barriers to hospice from a hospice provider
      perspective. We assessed such views via a postal survey to all licensed hospices
      in Alabama (N = 193)-response = 55.4%. Most providers considered physicians and
      health care professionals to be somewhat knowledgeable of hospice, but also
      indicated a lack of knowledge constituted the barrier with the most impact in
      their communities. Respondents also cited physician difficulties with discussing
      end of life with patients and prognosticating death within 6 months as leading
      barriers. Providers also described Medicare reimbursement cap issues that have
      resulted in barriers to hospice. Our findings were similar to previous
      investigations assessing provider perceptions. Future studies should explore how
      reimbursement cap issues affect the receipt and delivery of hospice care.

PMID- 20801921
TI  - Comfort measures: practical care of the dying cancer patient.
AB  - Most patients with advanced malignancy will die of their disease. Care of the
      dying is therefore a fundamental skill for the oncologist. Although protocols
      exist in other countries, there is no established protocol in the United States.
      We present a protocol for management of the dying that is clinically useful and
      review the existing evidence-base.

PMID- 20801922
TI  - Chromoplast differentiation: current status and perspectives.
AB  - Chromoplasts are carotenoid-accumulating plastids conferring color to many
      flowers and fruits as well as to some tubers and roots. Chromoplast
      differentiation proceeds from preexisting plastids, most often chloroplasts. One
      of the most prominent changes is remodeling of the internal membrane system
      associated with the formation of carotenoid-accumulating structures. During the
      differentiation process the plastid genome is essentially stable and
      transcriptional activity is restricted. The buildup of the chromoplast for
      specific metabolic characteristics is essentially dependent upon the
      transcriptional activity of the nucleus. Important progress has been made in
      terms of mediation of the chloroplast-to-chromoplast transition with the
      discovery of the crucial role of the Or gene. In this article we review recent
      developments in the structural, biochemical and molecular aspects of chromoplast
      differentiation and also consider the reverse differentiation of chromoplasts
      into chloroplast-like structures during the regreening process occurring in some
      fruit. Future perspectives toward a full understanding of chromoplast
      differentiation include in-depth knowledge of the changes occurring in the
      plastidial proteome during chromoplastogenesis, elucidation of the role of
      hormones and the search for signals that govern the dialog between the nuclear
      and the chromoplastic genome.

PMID- 20801923
TI  - Involvement of ethylene and hydrogen peroxide in induction of alternative
      respiratory pathway in salt-treated Arabidopsis calluses.
AB  - The role of ethylene and hydrogen peroxide (H2O2) in the induction of the
      alternative respiratory pathway (AP) in calluses from wild-type (WT) Arabidopsis
      and ethylene-insensitive mutant etr1-3 under salt stress was investigated. The
      capacity and the contribution of the AP to the total respiration were
      significantly induced by 100 mM sodium chloride (NaCl) in WT calluses but only
      slightly induced in etr1-3 calluses. Ethylene emission was enhanced in WT
      calluses under salt stress. Application of 1-aminocyclopropane-1-carboxylic acid
      (an ethylene precursor) further increased the AP capacity in WT calluses but not
      in etr1-3 calluses under salt stress. Reduction of ethylene production by
      aminooxyacetic acid (AOA, an ethylene biosynthesis inhibitor) in WT calluses
      eliminated the NaCl-induced increase of ethylene emission and inhibited AP
      induction under salt stress, suggesting that ethylene is required for AP
      induction. H2O2 enhanced ethylene production while ethylene reduced H2O2
      generation in WT calluses under salt stress. In addition, ethylene and H2O2
      modulated NaCl-induced alternative oxidase gene (AOX1a) expression and the
      increase in pyruvate content in WT calluses. Inhibition of the AP by
      salicylhydroxamic acid in WT calluses under salt stress resulted in severe
      cellular damage as indicated by the high content of H2O2, malondialdehyde and
      more electrolyte leakage. Taken together, ethylene and H2O2 are involved in the
      salt-induced increase of the AP, which plays an important role in salt tolerance
      in WT calluses, and ethylene may be acting downstream of H2O2.

PMID- 20801924
TI  - 2010 Focused Update of ESC Guidelines on device therapy in heart failure: an
      update of the 2008 ESC Guidelines for the diagnosis and treatment of acute and
      chronic heart failure and the 2007 ESC guidelines for cardiac and
      resynchronization therapy. Developed with the special contribution of the Heart
      Failure Association and the European Heart Rhythm Association.

PMID- 20801925
TI  - Transcatheter device closure of perimembranous ventricular septal defects: mid
      term outcomes.
AB  - AIMS: The aim of this study was to evaluate the safety and efficacy of
      transcatheter closure for perimembranous ventricular septal defect (pmVSD) and
      its long-term results. The most common congenital heart condition is pmVSD.
      Transcatheter closure of pmVSD is a recently described technique with limited
      results for mid- to long-term follow-up. METHODS AND RESULTS: Between June 2002
      and June 2008, 848 patients with pmVSD were enrolled in our study and treated
      percutaneously with pmVSD occluders. All patients were followed up until December
      2008, an average of 37 months. According to colour Doppler transthoracic
      echocardiography before the intervention and ventriculography, the average end
      diastolic pmVSD size was 5.1 and 5.4 mm, respectively. Placement of the device
      was successful in 832 patients (98.1%) and the median device size was 8.6 mm.
      During follow-up, 103 adverse events (12.4%) were reported. Most adverse events
      were categorized as minor and there were nine major adverse events (8.7%),
      including two complete atrioventricular block requiring pacemaker implantation.
      Kaplan-Meier estimates showed >85% freedom from major or minor adverse events
      during a maximal follow-up of 79 months. CONCLUSIONS: In experienced hands,
      transcatheter pmVSD closure can be performed safely and successfully with low
      morbidity and mortality. Long-term prognostic results are favourable, and the
      transcatheter approach provides a less-invasive alternative that may become the
      first choice in selected pmVSD patients. This trial is registered with
      ClinicalTrials.gov, number NCT00890799.

PMID- 20801926
TI  - Markers of renal function and acute kidney injury in acute heart failure:
      definitions and impact on outcomes of the cardiorenal syndrome.
AB  - AIMS: Acute kidney injury (AKI) in patients hospitalized for acute heart failure
      (AHF) is part of the cardiorenal syndrome and has been associated with increased
      morbidity and mortality. However, definitions and prognostic impact of AKI in AHF
      have been variable. Cystatin C is a prospective new marker of AKI. The objective
      of this study was to investigate the use of cystatin C as a marker of early AKI
      in AHF. METHODS AND RESULTS: Patients (n = 292) hospitalized for AHF had
      measurements of cystatin C on admission and at 48 h. We assessed the incidence of
      a rise in cystatin C between the two measurements and evaluated the effect of an
      increase in cystatin C on outcomes up to 12 months. The population was on average
      75 years old and 49% were female. On admission, median cystatin C was 1.25 mg/L
      (interquartile range 0.99-1.61 mg/L). A rise in cystatin C by >0.3 mg/L within 48
      h after hospitalization (AKI(cysC)) occurred in 16% of patients and resulted in 3
      days (P = 0.01) longer hospital stay and was associated with significantly higher
      in-hospital mortality, odds ratio 4.0 [95% confidence intervals (CI) 1.3-11.7, P
      = 0.01]. During follow-up, AKI(cysC) was an independent predictor of 90 days
      mortality, adjusted odds ratio 2.8 (95% CI 1.2-6.7, P = 0.02). CONCLUSION:
      Cystatin C appears to be a useful marker of early AKI in patients hospitalized
      for AHF. A decline in renal function detected by cystatin C during the first 48 h
      after hospitalization occurs frequently in AHF and has a detrimental impact on
      prognosis.

PMID- 20801927
TI  - ESC Guidelines for the management of grown-up congenital heart disease (new
      version 2010).

PMID- 20801928
TI  - Identification and analysis of type II TGF-beta receptors in BMP-9-induced
      osteogenic differentiation of C3H10T1/2 mesenchymal stem cells.
AB  - Our previous studies have demonstrated that bone morphogenetic protein 9 (BMP-9)
      is one of the most efficacious BMPs to induce osteoblast differentiation of
      mesenchymal stem cells (MSCs). However, the molecular mechanism underlying the
      BMP-9-induced osteogenic differentiation of MSCs remains to be fully elucidated.
      In this study, dominant negative (DN) type II TGF-beta receptors were constructed
      and introduced into C3H10T1/2 stem cells, then in vitro and in vivo assays were
      carried out to analyze and identify the type II TGF-beta receptors required for
      BMP-9-induced osteogenesis. We found that three DN type II TGF-beta receptors, DN
      BMPRII, DN-ActRII, and DN-ActRIIB, diminished BMP-9-induced alkaline phosphatase
      (ALP) activity, led to a decrease in BMP-9-induced Smad binding element (SBE)
      controled reporter activity, reduced BMP-9-induced expressions of Smad6 and
      Smad7, and decreased BMP-9-induced mineralization in vitro and ectopic bone
      formation in vivo, finally resulted in decreased bone masses and immature
      osteogenesis. These findings strongly suggested that three wild-type II TGF-beta
      receptors, BMPRII, ActRII and ActRIIB, may play a functional role in BMP-9
      induced osteogenic differentiation of C3H10T1/2 cells. However, C3H10T1/2 stem
      cells can express BMPRII and ActRII, but not ActRIIB. Using RNA interference
      (RNAi), we found that luciferase reporter activity and ALP activity induced by
      BMP-9 were accordingly inhibited along with the knockdown of BMPRII and ActRII.
      Taken together, our results demonstrated that BMPRII and ActRII are the
      functional type II TGF-beta receptors in BMP-9-induced osteogenic differentiation
      of C3H10T1/2 cells.

PMID- 20801929
TI  - Chemical synthesis and characterization of two alpha4/7-conotoxins.
AB  - alpha-Conotoxins are small disulfide-constrained peptides that act as potent and
      selective antagonists on specific subtypes of nicotinic acetylcholine receptors
      (nAChRs). We previously cloned two alpha-conotoxins, Mr1.1 from the
      molluscivorous Conus marmoreus and Lp1.4 from the vermivorous Conus leopardus.
      Both of them have the typical 4/7-type framework of the subfamily of alpha
      conotoxins that act on neuronal nAChRs. In this work, we chemically synthesized
      these two toxins and characterized their functional properties. The synthetic
      Mr1.1 could primarily inhibit acetylcholine (ACh)-evoked currents reversibly in
      the oocyte-expressed rat alpha7 nAChR, whereas Lp1.4 was an unexpected specific
      blocker of the mouse fetal muscle alpha1beta1gammadelta receptor. Although their
      inhibition affinities were relatively low, their unique receptor recognition
      profiles make them valuable tools for toxin-receptor interaction studies. Mr1.1
      could also suppress the inflammatory response to pain in vivo, suggesting that it
      should be further investigated with respect to its molecular role in analgesia
      and its mechanism or therapeutic target for the treatment of pain.

PMID- 20801930
TI  - Quantifying the amount of congestion in heart failure.

PMID- 20801935
TI  - The TCT motif, a key component of an RNA polymerase II transcription system for
      the translational machinery.
AB  - The TCT motif (polypyrimidine initiator) encompasses the transcription start site
      of nearly all ribosomal protein genes in Drosophila and mammals. The TCT motif is
      required for transcription of ribosomal protein gene promoters. The TCT element
      resembles the Inr (initiator), but is not recognized by TFIID and cannot function
      in lieu of an Inr. However, a single T-to-A substitution converts the TCT element
      into a functionally active Inr. Thus, the TCT motif is a novel transcriptional
      element that is distinct from the Inr. These findings reveal a specialized TCT
      based transcription system that is directed toward the synthesis of ribosomal
      proteins.

PMID- 20801936
TI  - Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR
      complexes.
AB  - We reported previously that the stability of all mammalian phosphatidylinositol 3
      kinase-related protein kinases (PIKKs) depends on their interaction with Tel2,
      the ortholog of yeast Tel2 and Caenorhabditis elegans Clk-2. Here we provide
      evidence that Tel2 acts with Hsp90 in the maturation of PIKK complexes.
      Quantitative immunoblotting showed that the abundance of Tel2 is low compared
      with the PIKKs, and Tel2 preferentially bound newly synthesized ATM, ATR, mTOR,
      and DNA-PKcs. Tel2 complexes contained, in addition to Tti1-Tti2, the Hsp90
      chaperone, and inhibition of Hsp90 interfered with the interaction of Tel2 with
      the PIKKs. Analysis of in vivo labeled nascent protein complexes showed that Tel2
      and Hsp90 mediate the formation of the mTOR TORC1 and TORC2 complexes and the
      association of ATR with ATRIP. The structure of yeast Tel2, reported here, shows
      that Tel2 consists of HEAT-like helical repeats that assemble into two separate
      alpha-solenoids. Through mutagenesis, we identify a surface patch of conserved
      residues involved in binding to the Tti1-Tti2 complex in vitro. In vivo, mutation
      of this conserved patch affects cell growth, levels of PIKKs, and ATM/ATR
      mediated checkpoint signaling, highlighting the importance of Tti1-Tti2 binding
      to the function of Tel2. Taken together, our data suggest that the Tel2-Tti1-Tti2
      complex is a PIKK-specific cochaperone for Hsp90.

PMID- 20801937
TI  - N-Acetyltransferase-2 (NAT2) gene polymorphisms and enzyme activity in Serbs:
      unprecedented high prevalence of rapid acetylators in a White population.
AB  - The aim of this study was to investigate N-acetyltransferase 2 (NAT2) genetic
      polymorphism and enzyme activity in Serbs, and to examine the influence of NAT2
      genotype, sex, and smoking on the phenotype. Genotyping for 190C>T, 282C>T,
      341T>C, 403C>G, 411T>A, 481C>T, 590G>A, 803A>G, and 857G>A in the NAT2 gene, was
      performed in 140 healthy Serbs. NAT2 activity was determined as AFMU/ (AFMU + 1X
      + 1U) urinary ratio in 100 subjects using caffeine as a probe. The most frequent
      NAT2 haplotypes were NAT2*5B (38.2%), NAT2*6A (26.0%), and NAT2*4 (24.4%). The
      log-transformed NAT2 activity indices exhibited trimodal distribution with 9%,
      36%, and 55% of slow, intermediate, and rapid acetylators, respectively.
      Significant NAT2 genotype-phenotype correlation was observed (P < .0001). The
      frequency of NAT1*10 and NAT1*11 were 27.5% and 6.9%, respectively. There was no
      significant influence of sex or cigarette smoking on NAT2 enzyme activity. Eight
      subjects displayed rapid NAT2 acetylators phenotype despite being homozygous for
      NAT2 slow alleles, and NAT1 fast acetylators genotype (NAT1*10 and NAT1*11) had
      no implication. In contrast to other white populations described hitherto, rapid
      acetylator is the predominant NAT2 phenotype in Serbs. NAT2 genotype, but not sex
      and cigarette smoking, influence enzyme activity. NAT1 fast acetylators genotypes
      do not contribute for NAT2 genotype-phenotype discordance.

PMID- 20801938
TI  - Riociguat (BAY 63-2521) and warfarin: a pharmacodynamic and pharmacokinetic
      interaction study.
AB  - Riociguat (BAY 63-2521) and warfarin are likely to be used concomitantly to treat
      pulmonary hypertension. The aim of this double-blind, crossover, clinical
      pharmacological study in 30 healthy volunteers was to investigate potential
      pharmacodynamic and pharmacokinetic interactions between the 2 drugs. Healthy
      volunteers took 2.5 mg of oral riociguat or matching placebo 3 times daily for 10
      days. A single oral dose of warfarin sodium (25 mg) was given 21 days before the
      study and on the seventh day of riociguat/placebo treatment. Twenty-one
      participants valid for safety analysis reported 89 treatment-emergent adverse
      events, all of mild or moderate severity. No serious adverse events occurred. The
      most frequently reported treatment-emergent adverse events considered to be drug
      related were dyspepsia, headache, flatulence, nausea, and vomiting. Twenty-two
      participants were valid for pharmacodynamic/pharmaco-kinetic analysis. Riociguat
      (2.5 mg 3 times daily) had no pharmacodynamic interaction with warfarin. Steady
      state plasma levels of riociguat did not affect prothrombin time, factor VII
      clotting activity, or the pharmacokinetics of warfarin. The single dose of
      warfarin led to a slight decrease (16%) in maximum concentration of riociguat in
      plasma, which is not likely to be clinically relevant. Clinical studies will
      confirm the finding here that combined use of riociguat with warfarin will not
      require dose adaptation.

PMID- 20801939
TI  - Understanding subfertility at a molecular level in the female through the
      application of nuclear magnetic resonance (NMR) spectroscopy.
AB  - BACKGROUND: Understanding the aetiology of subfertility and female reproductive
      tract disorders at a molecular level may improve success rates in fertility
      treatment. Such understanding may be gained by the application of metabonomics
      technologies to tissues or biofluids. Metabonomics is concerned with the
      quantification of molecules in the metabolome and uses nuclear magnetic resonance
      (NMR) spectroscopy as one of the main technological platforms. This review
      concentrates on NMR studies of the female reproductive tract and discusses
      further possible applications. While full metabolic profiling is relatively
      recent, targeted NMR studies of biofluid and tissue has a longer history.
      METHODS: Searches were carried out on MEDLINE((r)), PubMed, SciFinder((r))
      Scholar 2007 and ISI Web of Knowledge(SM) for papers about NMR spectroscopy or
      metabonomics of the female reproductive tract and subfertility. RESULTS: NMR
      spectroscopy has been employed for the compositional analysis of various elements
      of the female reproductive tract, including cervical mucus, follicular fluid
      (FF), ovarian tissue, fallopian tubes and uterine matter. NMR was used to
      document for the first time a change in FF lipoprotein concentration during
      follicular development. NMR analysis of granulosa cells from rats has revealed
      that follicle-stimulating hormone increases the activity of the pentose pathway,
      having crucial implications for ovarian stimulation regimens. In the uterine
      matter work, it has been shown by NMR that glycolysis is rapidly stimulated by
      estrogen, and in another study, citrate in uterine fluid was found as a potential
      biomarker for adenomyosis. NMR has also been used to show that chlamydiae are
      able to achieve higher energy reserves by stimulating glucose transport in host
      cells. CONCLUSIONS: A range of NMR spectroscopic techniques have been applied to
      the analysis of the female reproductive tract, however great potential remains
      for further studies. Incorporation of metabonomics techniques into female
      fertility research may be valuable for understanding subfertility and predicting
      outcomes of assisted conception treatments.

PMID- 20801940
TI  - The natural radioactivity contents in feed coals from the lignite-fired power
      plants in Western Anatolia, Turkey.
AB  - Lignite burning is one of the sources of technologically enhanced exposure to
      humans from natural radionuclides. In the preliminary study, part of the survey,
      the activity concentrations of (226)Ra, (232)Th and (40)K in 112 samples of feed
      lignites from seven lignite-fired power plants in Western Anatolia (Seyitomer,
      Tuncbilek, Orhaneli, Soma, Yatagan, Yenikoy and Kemerkoy) were, therefore,
      determined by scintillation gamma spectrometry. The ranges of the relevant
      radionuclides in the lignite samples are as follows: (226)Ra, 23-291 Bq kg(-1);
      (232)Th, 12-68 Bq kg(-1); and (40)K, 67-284 Bq kg(-1). Taking the coefficient of
      variation (CV) as a measure of the variability, the CV is also calculated for the
      natural radionuclides in the feed lignites. Furthermore, the dose rates in the
      coal-handling areas due to external gamma radiation are found to be within the
      range specified by UNSCEAR (2000) report.

PMID- 20801941
TI  - Efficacy of an olmesartan medoxomil-based treatment algorithm in patients with
      hypertension and type 2 diabetes: analysis of diurnal blood pressure control as
      assessed by 24-hour ambulatory blood pressure monitoring.
AB  - OBJECTIVE: Secondary, prespecified analysis of a single-arm, open-label study
      evaluating the efficacy of olmesartan medoxomil (OM) plus hydrochlorothiazide
      (HCTZ) in patients with hypertension and type 2 diabetes. METHODS: After placebo
      run-in, 192 patients received OM 20 mg/day for 3 weeks. If blood pressure (BP)
      remained >=120/70 mmHg, patients were uptitrated every 3 weeks to OM 40 mg/day,
      OM/HCTZ 40/12.5 mg/day, and OM/HCTZ 40/25 mg/day. Efficacy was evaluated by 24
      hour ambulatory BP monitoring. Secondary endpoints included changes in ambulatory
      systolic BP (SBP) and diastolic BP (DBP) during daytime (08:00 to 16:00) and
      nighttime (22:00 to 06:00), as well as achievement of prespecified ambulatory BP
      targets in the total cohort and subgroups based on gender, race, hypertension
      severity, and age (>=65 or <65 years). Dipper status (nocturnal decrease in BP
      >=10% of mean daytime BP) was assessed. RESULTS: At baseline, mean ambulatory BP
      was 151.2 +/- 12.7/87.6 +/- 9.0 mmHg during the daytime and 140.3 +/- 13.1/78.1
      +/- 8.6 mmHg during the nighttime. Mean daytime and nighttime ambulatory BP was
      reduced from baseline by 22.3 +/- 13.7/12.0 +/- 8.9 mmHg and 18.8 +/- 12.4/ 10.2
      +/- 7.2 mmHg, respectively. The reduction in daytime ambulatory SBP was 24.4 +/-
      11.8 mmHg in Blacks, 21.7 +/- 14.2 mmHg in non-Blacks, 23.6 +/- 12.3 mmHg in
      females, 21.2 +/- 14.8 mmHg in males, 23.4 +/- 11.6 mmHg in patients aged >=65
      years, and 21.9 +/- 14.4 mmHg in those aged <65 years. Ambulatory BP targets of
      <130/80, <125/75, and <120/80 mmHg were reached by 51.7%, 36.0%, and 32.6% of
      patients during the daytime and 69.8%, 60.5%, and 50.6% of patients during the
      nighttime. After 12 weeks of treatment, 36.4% of baseline nondippers converted to
      dippers. CONCLUSIONS: OM +/- HCTZ effectively lowered ambulatory BP in patients
      with type 2 diabetes and hypertension, enabling them to achieve ambulatory BP
      targets during both the daytime and nighttime.

PMID- 20801942
TI  - A quasi-experimental feasibility study to determine the effect of a systematic
      treatment programme on the scores of the Nottingham Adjustment Scale of
      individuals with visual field deficits following stroke.
AB  - OBJECTIVE: To evaluate a systematic treatment programme developed by the
      researcher that targeted aspects of visual functioning affected by visual field
      deficits following stroke. DESIGN: The study design was a non-equivalent control
      (conventional) group pretest-posttest quasi-experimental feasibility design,
      using multisite data collection methods at specified stages. SETTING: The study
      was undertaken within three acute hospital settings as outpatient follow-up
      sessions. SUBJECTS: Individuals who had visual field deficits three months post
      stroke were studied. INTERVENTIONS: A treatment group received routine
      occupational therapy and an experimental group received, in addition, a
      systematic treatment programme. The treatment phase of both groups lasted six
      weeks. MAIN MEASURES: The Nottingham Adjustment Scale, a measure developed
      specifically for visual impairment, was used as the primary outcome measure.
      RESULTS: The change in Nottingham Adjustment Scale score was compared between the
      experimental (n = 7) and conventional (n = 8) treatment groups using the Wilcoxon
      signed ranks test. The result of Z = -2.028 (P = 0.043) showed that there was a
      statistically significant difference between the change in Nottingham Adjustment
      Scale score between both groups. CONCLUSIONS: The introduction of the systematic
      treatment programme resulted in a statistically significant change in the scores
      of the Nottingham Adjustment Scale.

PMID- 20801943
TI  - Visual field expansion after visual restoration therapy.
AB  - OBJECTIVE: To determine whether visual field expansion occurs with visual
      restoration therapy (VRT), using fundus-controlled microperimetry to assess
      visual fields. DESIGN: This longitudinal cohort analysis assesses patients'
      visual fields before and after visual restoration therapy using microperimetry
      and standard high-resolution perimetry. SUBJECTS: Seven patients with stroke
      induced homonymous field cuts were studied. INTERVENTION: Visual restoration
      therapy is a computerized, home-based treatment aimed at reducing the size of the
      visual field defect of stroke patients with hemianopia through repetitive
      stimulation of the visual borderzone adjacent to the blind field. During twice
      daily therapy for three months patients maintain central fixation while
      responding to eccentrically placed stimuli in the visual borderzone. The
      programme is adjusted monthly to changes in the patient's visual field.
      Controversy exists as to whether expansion of visual fields measured at home with
      high-resolution perimetry is due to inadvertent eye movements and therefore would
      overrepresent the treatment's effect. MAIN MEASURES: Microperimentry uses an
      infrared camera to track retinal vessels so that any shift or movement between
      the reference image and the real-time fundus image corrects the stimulus
      position, thus delivering stimuli to known retinal locations, and allowing
      accurate assessment of visual fields independent of eye movements. RESULTS: There
      was an average improvement in stimulus detection rate by microperimetry of 12.5%
      (range -1.4% to 38.9%, P =0.033). Six of 7 patients had >= 3% improvement in
      stimulus detection by home-based perimetry. CONCLUSION: Our results demonstrate
      modest but real expansion in visual fields following visual restoration therapy
      which is not due to eye movements.

PMID- 20801944
TI  - The role of religiosity, coping strategies, self-efficacy and personality
      dimensions in the prediction of Iranian undergraduate rehabilitation interns'
      satisfaction with their clinical experience.
AB  - OBJECTIVE: to investigate the relationship between religiosity, coping styles,
      self-efficacy and personality dimensions as predictors of satisfaction with
      clinical experience in rehabilitation interns during transition from academic
      study to clinical internship. DESIGN: a cross-sectional survey design. SETTING:
      five rehabilitation faculties. PARTICIPANTS: three hundred and eighteen
      undergraduate rehabilitation interns, including physical therapy, occupational
      therapy and speech and language pathology students. MAIN OUTCOME MEASURES:
      Islamic Religiosity Scale, Ways of Coping Questionnaire, General Self-efficacy
      Scale, NEO Five Factor Inventory, and Satisfaction with Clinical Experiences
      Questionnaire. RESULTS: religiosity, problem-focused coping and general self
      efficacy had significant positive correlation with satisfaction with clinical
      internship in rehabilitation students. Among personality dimensions, openness,
      agreement and consciousness had significant positive correlation with
      satisfaction with clinical experience and neuroticism had significant negative
      correlation with satisfaction with clinical experience. The results of regression
      analysis demonstrated that religiosity and self-efficacy had important roles in
      the prediction of satisfaction with clinical experience in all the rehabilitation
      intern students of three disciplines (physical therapy, occupational therapy, and
      speech and language pathology). CONCLUSION: religiosity, problem-focused coping
      and general self-efficacy seem to be good predictors of satisfaction with
      clinical internship in rehabilitation students.

PMID- 20801945
TI  - The Ways of Coping Checklist (WCC): validation in French-speaking cancer
      patients.
AB  - We explore the psychometric properties of the French version of the Ways of
      Coping Checklist Revised (WCC-R) for a cancer patient sample. The WCC-R was
      completed by 622 patients and 464 completed the State-Trait Anxiety Inventory
      (STAI). A confirmatory factor analysis (CFA) on the original factor structure did
      not fit the data. The sample was randomly divided into two subsamples.
      Exploratory factor analysis was conducted on one subsample and revealed three
      factors: 'Seeking social support', 'Problem focused-coping' and 'Self-blame and
      avoidance', including 21 items. A CFA confirmed this structure in the second
      subgroup. These scales correlated with the anxiety scores.

PMID- 20801946
TI  - Barriers to adherence to antiretroviral treatment: the perspectives of patient
      advocates.
AB  - Patient advocates were asked for their perspectives on the structural barriers to
      adherence to antiretroviral treatment among patients living with HIV. Poverty
      related barriers were transport difficulties, food insecurity and patients'
      receipt of a disability grant. Institutional barriers were long waiting times at
      clinics, negative experiences with clinic staff, low levels of health literacy
      and poor access to substance abuse treatment. Social and cultural barriers were
      the role of traditional healing practices, the influence of charismatic churches
      and perceived stigmatization. We offer a perspective on assisting patients living
      with HIV in addressing these key structural barriers to adherence.

PMID- 20801947
TI  - Community-building: a strategy to address inequality of health in Australia.
AB  - Given the improvements in the health of Australians in recent decades, not all
      sectors of populations have benefited equally. Inequality and poverty are major
      problems. Traditional hierarchical, top-down governance seems ineffective to
      address these complex problems. An innovative and more participatory community
      based approach is called for to address these issues. Community-building
      approaches, characterized by wide-ranging community involvement, emphasizing
      strength and collaboration, can be a good vehicle and intervention strategy to
      address the poverty problem by empowering both the individual and the community.
      The relevance of the community-building approach to the poverty issue and
      Australian context is discussed.

PMID- 20801948
TI  - Protective effects of organic solvent fractions from the seeds of Vigna radiata
      L. wilczek against antioxidant mechanisms.
AB  - This study was conducted to evaluate the in vitro scavenging activity and
      inhibitory effect of low-density lipoprotein oxidation of pro-oxidant reactive
      species in response to treatment with organic solvent fractions from mung bean
      (seeds of Vigna radiata) extracts using various screening methods including
      biological and non-biological oxidants. The antioxidant activity of different
      organic solvent fractions from mung bean extracts were studied in vitro methods
      by evaluating the total phenol components, measuring the antioxidant activity by
      trolox equivalent antioxidant capacity, measuring the scavenging effects on
      reactive oxygen species and on reactive nitrogen species as well as measuring the
      inhibitory effect on Cu(2+)-induced human low-density lipoprotein oxidation. The
      mung bean extracts were found to have a potent scavenging activity against all of
      the reactive species tested as well as an inhibitory effect on low-density
      lipoprotein oxidation, the studied mung bean was revealed to be very effective
      against the evaluated pro-oxidant species, including reactive oxygen species and
      on reactive nitrogen species.

PMID- 20801949
TI  - Effect of different doses of un-fractionated green and black tea extracts on
      thyroid physiology.
AB  - Tea is a rich source of polyphenolic flavonoids including catechins, which are
      thought to contribute to the health benefits of it. Flavonoids have been reported
      to have antithyroid and goitrogenic effect. The purpose of this study was to
      evaluate whether high doses of green and black tea have a harmful effect on
      thyroid physiology. Un-fractionated green and black tea extracts were
      administered orally to male rats for 30 days at doses of 1.25 g%, 2.5 g% and 5.0
      g%. The results showed that green tea extract at 2.5 g% and 5.0 g% doses and
      black tea extract only at 5.0 g% dose have the potential to alter the thyroid
      gland physiology and architecture, that is, enlargement of thyroid gland as well
      as hypertrophy and/or hyperplasia of the thyroid follicles and inhibition of the
      activity of thyroid peroxidase and 5(')-deiodinase I with elevated thyroidal Na+,
      K+-ATPase activity along with significant decrease in serum T3 and T4, and a
      parallel increase in serum thyroid stimulating hormone (TSH). This study
      concludes that goitrogenic/antithyroidal potential of un-fractionated green tea
      extract is much more than black tea extract because of the differences in
      catechin contents in the tea extracts.

PMID- 20801950
TI  - Protective potential of 17beta-estradiol against co-exposure of 4-hydroxynonenal
      and 6-hydroxydopamine in PC12 cells.
AB  - 4-hydroxynonenal (4-HNE) and 6-hydroxydopamine (6-OHDA)-mediated damage in
      dopaminergic neurons is well documented. Protective potential of steroidal
      hormone (17beta-estradiol) has also been suggested. However, therapeutic
      potential of such promising hormone is hampered due to complex brain anatomy and
      physiology. Thus, the present investigations were studied to suggest the
      applicability of dopamine expressing PC12 cells as in vitro tool to screen the
      pharmacological potential of 17beta-estradiol against 4-HNE and 6-OHDA. MTT assay
      was conducted for cytotoxicity assessment of both 4-HNE (1 MUM to 50 MUM) and 6
      OHDA (10(-4) to 10(-7) M). Non-cytotoxic concentrations, that is, 4-HNE (1 MUM)
      and 6-OHDA (10(-6) M) were selected to study the synergetic/additive responses.
      PC12 cells were found to be more vulnerable towards co-exposure of individual
      exposure of 4-HNE and 6-OHDA, even at non-cytotoxic concentrations. Then, cells
      were subjected to pre-treatment (24 hours) of 17beta-estradiol (1 MUM), followed
      by a permutation of combinations of both 4-HNE and 6-OHDA. Pretreatment of 17beta
      estradiol was found to be significantly effective against the cytotoxic responses
      of 4-HNE and 6-OHDA, when the damage was at lower level. However, 17beta
      estradiol was found to be ineffective against higher concentrations.
      Physiological-specific responses of PC12 cells against 4-HNE/6-OHDA and 17beta
      estradiol suggest its applicability as first tier of screening tool.

PMID- 20801952
TI  - The RET polymorphic allele S836S is associated with early metastatic disease in
      patients with hereditary or sporadic medullary thyroid carcinoma.
AB  - The possible role of RET variants in modifying the natural course of medullary
      thyroid carcinoma (MTC) is still a matter of debate. Here, we investigate whether
      the RET variants L769L, S836S, and G691S/S904S influence disease presentation in
      hereditary or sporadic MTC patients. One hundred and two patients with hereditary
      MTC and 81 patients with sporadic MTC attending our institution were evaluated.
      The frequencies of RET polymorphisms in hereditary MTC were as follows: L769L,
      17.3%; S836S, 7.95%; and S904S/G691S, 18.2%. No associations were observed
      between these polymorphisms and pheochromocytoma, hyperparathyroidism, lymph
      node, or distant metastasis. However, patients harboring the S836S variant were
      younger than those without this allele (17+/-8.2 vs 28.6+/-14.4 years, P=0.01),
      suggesting that these patients had metastases at a young age. Accordingly, the
      cumulative frequency of local and/or distant metastases as estimated by Kaplan
      Meier curves showed that lymph node and distant metastases occurred earlier in
      patients harboring the S836S variant (P=0.003 and P=0.026 respectively). The
      S836S allele frequency was higher in sporadic MTC patients than in controls (10.5
      vs 3.1%, P=0.01). Individuals harboring the S836S variant were younger (38.6+/
      13.3 vs 48.5+/-16.7 years, P=0.02) and showed a higher percentage of lymph node
      and distant metastases (P=0.02 and P=0.04 respectively). Kaplan-Meier estimates
      of lymph node and distant metastases yielded distinct curves for patients with or
      without the S836S allele (P=0.002 and P=0.001 respectively). Additional analyses
      using a COX regression model showed that the S836S variant was independently
      associated with metastatic disease (hazard ratio 2.82 (95% confidence interval
      1.51-5.26), P=0.001). In conclusion, the RET S836S variant is associated with
      early onset and increased risk for metastatic disease in patients with hereditary
      or sporadic MTC.

PMID- 20801953
TI  - Diverse physiological functions of MKK4 and MKK7 during early embryogenesis.
AB  - Mitogen-activated protein kinase kinases (MAPKKs) are important components of the
      stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) signalling
      pathway. Two MAPKKs that are crucial transducers upstream of JNK signalling are
      MKK4 and MKK7. These two MAPKKs directly phosphorylate specific Tyr and Thr
      residues located in the activation loop of the JNK protein and activate this
      kinase in response to environmental stress, pro-inflammatory cytokines or
      developmental cues. Although much is known about the biochemical and structural
      bases of the catalytic mechanism of the MAPKKs, the regulation and physiological
      functions of these enzymes during early embryogenesis have remained a mystery
      until relatively recently. Studies employing a range of animal models have now
      revealed the essential roles that MAPKKs play in diverse developmental contexts,
      including in dorsoventral patterning, convergent extension and somitogenesis.
      Focusing primarily on extensive work done in mouse and zebrafish models, this
      review summarizes the functional properties of MKK4 and MKK7 during vertebrate
      and invertebrate development, and the mechanisms by which these kinases regulate
      multiple steps in the establishment of the body plan of an organism.

PMID- 20801951
TI  - Mammalian target of rapamycin inhibition abrogates insulin-mediated mammary tumor
      progression in type 2 diabetes.
AB  - Type 2 diabetes increases breast cancer risk and mortality, and hyperinsulinemia
      is a major mediator of this effect. The mammalian target of rapamycin (mTOR) is
      activated by insulin and is a key regulator of mammary tumor progression.
      Pharmacological mTOR inhibition suppresses tumor growth in numerous mammary tumor
      models in the non-diabetic setting. However, the role of the mTOR pathway in type
      2 diabetes-induced tumor growth remains elusive. Herein, we investigated whether
      the mTOR pathway is implicated in insulin-induced mammary tumor progression in a
      transgenic mouse model of type 2 diabetes (MKR mice) and evaluated the impact of
      mTOR inhibition on the diabetic state. Mammary tumor progression was studied in
      the double transgenic MMTV-Polyoma Virus middle T antigen (PyVmT)/MKR mice and by
      orthotopic inoculation of PyVmT- and Neu/ErbB2-driven mammary tumor cells (Met-1
      and MCNeuA cells respectively). mTOR inhibition by rapamycin markedly suppressed
      tumor growth in both wild-type and MKR mice. In diabetic animals, however, the
      promoting action of insulin on tumor growth was completely blunted by rapamycin,
      despite a worsening of the carbohydrate and lipid metabolism. Taken together,
      pharmacological mTOR blockade is sufficient to abrogate mammary tumor progression
      in the setting of hyperinsulinemia, and thus mTOR inhibitors may be an attractive
      therapeutic modality for breast cancer patients with type 2 diabetes. Careful
      monitoring of the metabolic state, however, is important as dose adaptations of
      glucose- and/or lipid-lowering therapy might be necessary.

PMID- 20801954
TI  - The ethics of mutuality.

PMID- 20801955
TI  - Clinical ethics and challenges to individualized care.

PMID- 20801956
TI  - A tribute to Paul Wainwright: 9 February 1948-16 June 2010.

PMID- 20801958
TI  - Courage and nursing practice: a theoretical analysis.
AB  - This article aims to deepen the understanding of courage through a theoretical
      analysis of classical philosophers' work and a review of published and
      unpublished empirical research on courage in nursing. The authors sought answers
      to questions regarding how courage is understood from a philosophical viewpoint
      and how it is expressed in nursing actions. Four aspects were identified as
      relevant to a deeper understanding of courage in nursing practice: courage as an
      ontological concept, a moral virtue, a property of an ethical act, and a creative
      capacity. The literature review shed light on the complexity of the concept of
      courage and revealed some lack of clarity in its use. Consequently, if courage is
      to be used consciously to influence nurses' ethical actions it seems important to
      recognize its specific features. The results suggest it is imperative to foster
      courage among nurses and student nurses to prepare them for ethical, creative
      action and further the development of professional nursing practices.

PMID- 20801959
TI  - Dare we speak of ethics? Attending to the unsayable amongst nurse leaders.
AB  - There is increasing emphasis on the need for collaboration between practice and
      academic leaders in health care research. However, many problems can arise owing
      to differences between academic and clinical goals and timelines. In order for
      research to move forward it is important to name and address these issues early
      in a project. In this article we use an example of a participatory action
      research study of ethical practice in nursing to highlight some of the issues
      that are not frequently discussed and we identify the impact of things not-named.
      Further, we offer our insights to others who wish to be partners in research
      between academic and practice settings. These findings have wide implications for
      ameliorating misunderstandings that may develop between nurse leaders in light of
      collaborative research, as well as for participatory action research.

PMID- 20801960
TI  - Moral obligations of nurses and physicians in neonatal end-of-life care.
AB  - The aim of this study was to explore the obligations of nurses and physicians in
      providing end-of-life care. Nineteen nurses and 11 physicians from a single
      newborn intensive care unit participated. Using content analysis, an overarching
      obligation of creating the best possible experience for infants and parents was
      identified, within which two categories of obligations (decision making and the
      end of life itself) emerged. Obligations in decision making included talking to
      parents and timing withdrawal. End-of-life obligations included providing
      options, preparing parents, being with, advocating, creating peace and normalcy,
      and providing comfort. Nurses and physicians perceived obligations in both
      categories, although nurse obligations centered on the end of life while
      physician obligations focused on decision making. The findings demonstrate that,
      although the ultimate goal is shared by both disciplines, the paths to achieving
      that goal are often different. This has important implications for collaboration,
      communication, and improving the end of life.

PMID- 20801961
TI  - Ethical vulnerabilities in nursing history: conflicting loyalties and the patient
      as 'other'.
AB  - The purpose of this article is to explore enduring ethical vulnerabilities of the
      nursing profession as illustrated in historical chapters of nursing's past. It
      describes these events, then explores two ethical vulnerabilities in depth:
      conflicting loyalties and duties, and relationships with patients as 'other'. The
      article concludes with suggestions for more ethical approaches to the other in
      current nursing practice. The past may be one of the most fruitful sites for
      examining enduring ethical vulnerabilities of the nursing profession. First of
      all, professional identity, which includes moral identity, comes in part from
      knowledge of the nursing profession's past. Second, looking to the past to
      understand better how events and ideologies have brought vulnerabilities to the
      fore raises questions about ethical nursing practice today.

PMID- 20801962
TI  - Mentoring overseas nurses: barriers to effective and non-discriminatory mentoring
      practices.
AB  - In this article it is argued that there are barriers to effective and non
      discriminatory practice when mentoring overseas nurses within the National Health
      Service (NHS) and the care home sector. These include a lack of awareness about
      how cultural differences affect mentoring and learning for overseas nurses during
      their period of supervised practice prior to registration with the UK Nursing and
      Midwifery Council. These barriers may demonstrate a lack of effective teaching of
      ethical practice in the context of cultural diversity in health care. This
      argument is supported by empirical data from a national study. Interviews were
      undertaken with 93 overseas nurses and 24 national and 13 local managers and
      mentors from six research sites involving UK health care employers in the NHS and
      independent sectors in different regions of the UK. The data collected showed
      that overseas nurses are discriminated against in their learning by poor
      mentoring practices; equally, from these data, it appears that mentors are ill
      equipped by existing mentor preparation programmes to mentor overseas-trained
      nurses from culturally diverse backgrounds. Recommendations are made for
      improving mentoring programmes to address mentors' ability to facilitate learning
      in a culturally diverse workplace and thereby improve overseas nurses'
      experiences of their supervised practice.

PMID- 20801963
TI  - Nurses' perceptions of individual and organizational political reasons for
      horizontal peer bullying.
AB  - Nurses are exposed to bullying for various reasons. It has been argued that the
      reason for bullying can be political, meaning that the behavior occurs to serve
      the self-interests of the perpetrators. This study aims to identify how nurses
      perceive the relevance of individual and political reasons for bullying
      behaviors. In February 2009 a survey was conducted with nurses working in a
      research and training hospital located in Turkey. The results showed that the aim
      of influencing promotion, task assignments, performance appraisal, recruitment,
      dismissal, allocation of equipment and operational means, together with
      allocation of personal benefits and organizational structure decisions, were
      perceived as potential political reasons for bullying by nurses. Moreover, the
      reasons for the various bullying behaviors were perceived as relevant to
      individual characteristics, namely, the perpetrators' need for power, and their
      psychological and private life problems.

PMID- 20801964
TI  - A theoretical examination of the rights of nurses.
AB  - Nurses' duties and patients' rights have been important foci in nursing. Nurses'
      rights legitimate the power and responsibility of the profession. There are few
      published articles on this subject in the nursing science literature. This
      article is a theoretical examination of nurses' rights that aims to structure
      (i.e. show the internal logic of) those that have been little studied. It is
      based on the philosophical literature and published research. Nurses' rights can
      be divided into: human and civil rights, rights based on health care legislation,
      professional rights, and earned rights. In this context, professional rights
      relate to nursing and also to tasks shared with other health care professions.
      Analyzing nurses' rights will help to promote these rights, improve nurses'
      position both nationally and internationally, and provide possibilities for
      enhancing patient care.

PMID- 20801965
TI  - Battlefield conditions: different environment but the same duty of care.
AB  - Using an interpretative research approach to ethical and legal literature, it is
      argued that nursing in the battlefield is distinctly different to civilian
      nursing, even in an emergency, and that the environment is so different that a
      duty of care owed by military nurses to wounded soldiers should not apply. Such
      distinct differences in wartime can override normal peacetime professional ethics
      to the extent that the duty of care owed by military nurses to their patients on
      the battlefield should not exist. It is also argued that as military nurses have
      legal and professional obligations to care for wounded soldiers on the
      battlefield, this obligation conflicts with following military orders, causing a
      dual loyalty conflict. This is because soldiers are part of the 'fighting force'
      and must be fit to fight and win the battle. This makes them more of a commodity
      rather than individual persons with distinct health care needs.

PMID- 20801966
TI  - Changes in Taiwanese nursing student values during the educational experience.
AB  - Professional values are standards for action and provide a framework for
      evaluating behavior. This study examined changes in the professional values of
      nursing students between their entrance to and graduation from an undergraduate
      nursing program. A pre- and post-test design was employed. A convenience sample
      of 94 students from a university in Taiwan was surveyed. Data were collected from
      students during the sophomore and senior years. Total scores obtained for the
      revised Nurses Professional Values Scale during the senior year of the nursing
      program were significantly higher than upon program entry. The 'caring' subscale
      was scored highest at both program entry and graduation, but the pre- and post
      test scores were not significantly different from each other. The students scored
      significantly higher on the 'professionalism' and 'activism' subscales at post
      test than they did at pre-test. Professional values changed in a positive
      direction between the beginning of the student nurses' educational experience and
      their graduation. The results supported the premise that education had a positive
      effect on these students' professional values but causality could not be assumed.

PMID- 20801967
TI  - Ethical openings in palliative home care practice.
AB  - Understanding how a nurse acts in a particular situation reveals how nurses enact
      their ethics in day-to-day nursing. Our ethical frameworks assist us when we
      experience serious ethical dilemmas. Yet how a nurse responds in situations of
      daily practice is contingent upon all the presenting cues that build the current
      moment. In this article, we look at how a home care nurse responds to the ethical
      opening that arises when the nurse enters a person's home. We discuss how the
      home presents the nurse with knowledge that informs the provision of ethical
      nursing care. The analysis is based on findings from an interpretive research
      study in palliative home care in Canada. Through interpretive analysis of a
      nursing situation we delineate how the nurse engages with the whole and acts
      inside the moment. The analysis shows how home care nurses are ethically
      determined to engage with whatever is going on in a patient's home.

PMID- 20801968
TI  - Nursing in Iran.

PMID- 20801969
TI  - Broken promises and the bad patient.

PMID- 20801970
TI  - Editorial Board Member, Doug Olsen, interviewed by Ann Gallagher.

PMID- 20801971
TI  - Introduction to issue on professional competence-related concerns.

PMID- 20801972
TI  - A critical appraisal of standard guidelines for grading levels of evidence.
AB  - Over the past 30 years, a general consensus has emerged within the medical
      community regarding the essential role served by grading guidelines in evaluating
      the quality of evidence produced by a medical research study. Specifically,
      consensus exists regarding the hierarchy of evidence, where randomized controlled
      trials (RCTs) are considered the ''gold standard'' followed by nonrandomized
      controlled trials (non-RCTs) and uncontrolled trials. As guidelines have become
      more sophisticated, processes have been developed for downgrading poorly
      conducted studies and upgrading strong studies. Lists of threats to internal
      validity have been disseminated, thereby assisting reviewers in grading studies.
      However, despite these many accomplishments, considerable issues remain
      unresolved with respect to how to evaluate the strength of evidence produced by
      flawed RCTs versus well-conducted non-RCTs. The purpose of this article is to
      evaluate existing evidence-based grading guidelines and to offer suggestions for
      how such guidelines may be improved.

PMID- 20801973
TI  - Use of evidence-based therapy for the prevention of cardiovascular events among
      older people.
AB  - Evidence-based therapies (EBTs) for the prevention of cardiovascular disease
      (CVD) are reportedly underutilized in older people. The primary purpose of this
      study was to evaluate the use of EBTs for the prevention of CVD events in older
      people and secondarily whether a Home Medicines Review (HMR) service by
      pharmacists' predicts the use of these medicines. A retrospective cross-sectional
      audit of HMR reports pertaining to 608 community-dwelling older people (>or=65
      years) was conducted. EBTs considered for this audit included four guideline
      recommended therapies for CVD: antithrombotic therapy (warfarin +/- antiplatelet
      therapy), beta-blockers, statins, and angiotensin agents (angiotensin-converting
      enzyme inhibitors [ACEI] +/- angiotensin II receptor blockers [ARBs]). The
      prevalence of EBT use among the older people, mean age (SD) 75.6 (7.5) years,
      was: 73% for antithrombotic therapy, 75% for statins, 74% for angiotensin
      therapy, and 35% for beta-blockers. CVD risk factors warranting treatment with
      these EBTs were frequently associated with use of EBTs. EBTs were least likely to
      be used in those with coronary interventions like coronary artery bypass grafting
      (CABG)/stent insertion (all EBTs except angiotensin agents) and angiotensin
      agents in those with a history of myocardial infarction or chronic heart failure.
      A pharmacist-led HMR service was significantly associated with the prescribing of
      all 4 EBTs. The results from this study show good adherence to evidence-based
      guidelines in general, although there is still room for improvement to further
      optimize clinical outcomes in these complex patients. The study also adds to the
      available literature on the effectiveness of pharmacists' collaborative
      contribution to the care of these high-risk patients.

PMID- 20801974
TI  - Measuring physicians' performance in clinical practice: reliability,
      classification accuracy, and validity.
AB  - Much research has been devoted to addressing challenges in achieving reliable
      assessments of physicians' clinical performance but less work has focused on
      whether valid and accurate classification decisions are feasible. This study used
      957 physicians certified in internal medicine (IM) or a subspecialty, who
      completed the American Board of Internal Medicine (ABIM) Diabetes Practice
      Improvement Module (PIM). Ten clinical and two patient-experience measures were
      aggregated into a composite measure. The composite measure score was highly
      reliable (r = .91) and classification accuracy was high across the entire score
      scale (>0.90), which indicated that it is possible to differentiate high
      performing and low-performing physicians. Physicians certified in endocrinology
      and those who scored higher on their IM certification examination had higher
      composite scores, providing some validity evidence. In summary, it is feasible to
      create a psychometrically robust composite measure of physicians' clinical
      performance, specifically for the quality of care they provide to patients with
      diabetes.

PMID- 20801975
TI  - Satisfaction of patients and primary care physicians with shared decision making.
AB  - Satisfaction with treatment is regarded as an important outcome measure, but its
      suitability has not been thoroughly investigated in the context of shared
      decision making (SDM). The authors evaluated whether both patients' and
      physicians' satisfaction ratings differ between an intervention group and a
      control group within a structured tool for cardiovascular prevention (ARRIBA
      Herz). In a pragmatic, cluster-randomized, controlled trial, 44 family physicians
      in the intervention group consecutively recruited 550 patients whereas 47
      physicians in the control group included 582 patients. Main findings were high
      satisfaction ratings independent of group allocation in patients and physicians.
      Significant differences had only negligible effect sizes. Compared to global
      satisfaction ratings, the effects of the shared decision-making process are
      better measured by a more concrete approach representing different steps of this
      process. Further research should refine behaviorally oriented questionnaires that
      measure SDM and a version for physicians should also be created.

PMID- 20801976
TI  - Quality and coordination of care for patients with multiple conditions: results
      from an international survey of patient experience.
AB  - Previous studies using clinical performance measures suggest that quality of care
      for patients with multiple chronic conditions is not worse than that for others.
      This article presents patient-reported experiences of health care among 8,973 of
      chronically ill adults from eight countries, using telephone survey data. We
      designed a ''morbidity score'' combining the number of conditions and reported
      health status. Respondents with high morbidity scores reported less favorable
      experience with coordination of care compared to those with low morbidity scores.
      They also reported lower ratings of overall quality of care. There were no
      differences in reported experience with the individual physicians. Comparing type
      of comorbidity, chronic lung, and mental health problems were associated with
      lower ratings than hypertension, heart disease, diabetes, arthritis, and cancer.
      The implications and limitations of this study are discussed in the context of
      health care reform. Pay-for-performance programs need to account for chronic
      conditions to avoid penalizing physicians who care for larger shares of such
      patients.

PMID- 20801977
TI  - Assessing implicit gender bias in Medical Student Performance Evaluations.
AB  - For medical schools, the increasing presence of women makes it especially
      important that potential sources of gender bias be identified and removed from
      student evaluation methods. Our study looked for patterns of gender bias in
      adjective data used to inform our Medical Student Performance Evaluations
      (MSPEs). Multigroup Confirmatory Factor Analysis (CFA) was used to model the
      latent structure of the adjectives attributed to students (n = 657) and to test
      for systematic scoring errors by gender. Gender bias was evident in two areas:
      (a) women were more likely than comparable men to be described as
      ''compassionate,'' ''sensitive,'' and ''enthusiastic'' and (b) men were more
      likely than comparable women to be seen as ''quick learners.'' The gender gap in
      ''quick learner'' attribution grows with increasing student proficiency; men's
      rate of increase is over twice that of women's. Technical and nontechnical
      approaches for ameliorating the impact of gender bias on student recommendations
      are suggested.

PMID- 20801978
TI  - The second time around: accounting for retest effects on oral examinations.
AB  - Years of research with high-stakes written tests indicates that although repeat
      examinees typically experience score gains between their first and subsequent
      attempts, their pass rates remain considerably lower than pass rates for first
      time examinees. This outcome is consistent with expectations. Comparable studies
      of the performance of repeat examinees on oral examinations are lacking. The
      current research evaluated pass rates for more than 50,000 examinees on written
      and oral exams administered by six medical specialty boards for several recent
      years. Pass rates for first-time examinees were similar for both written and oral
      exams, averaging about 84% across all boards. Pass rates for repeat examinees on
      written exams were expectedly lower, ranging from 22% to 51%, with an average of
      36%. However, pass rates for repeat examinees on oral exams were markedly higher
      than for written exams, ranging from 53% to 77%, with an average of 65%. Four
      explanations for the elevated repeat pass rates on oral exams are proposed,
      including an increase in examinee proficiency, construct-irrelevant variance,
      measurement error (score unreliability), and memorization of test content.
      Simulated data are used to demonstrate that roughly one third of the score
      increase can be explained by measurement error alone. The authors suggest that a
      substantial portion of the score increase can also likely be attributed to
      construct-irrelevant variance. Results are discussed in terms of their
      implications for making pass-fail decisions when retesting is allowed. The
      article concludes by identifying areas for future research.

PMID- 20801980
TI  - Pregnant asylum seekers.

PMID- 20801981
TI  - Asylum seekers' health needs. Transfer care to the NHS.

PMID- 20801982
TI  - Asylum seekers' health needs. With what right do we detain?

PMID- 20801983
TI  - Asylum seekers' health needs. Inhumane starting point.

PMID- 20801984
TI  - Home v hospital birth. Recent meta-analysis is misleading.

PMID- 20801985
TI  - Promoting self care. NHS Direct plays a major role.

PMID- 20801986
TI  - Minimum alcohol price. Good supporting evidence exists.

PMID- 20801988
TI  - NICE on bacterial meningitis. Vancomycin may not be necessary.

PMID- 20801989
TI  - Suicide and euthanasia paradox. A question of rights.

PMID- 20801990
TI  - Suicide and euthanasia paradox. Between blind rebuttal and the knacker's bolt.

PMID- 20801992
TI  - Referral management centres. Time for free flow of care.

PMID- 20801994
TI  - Precarious beginnings: Gendered risk discourses in psychiatric research
      literature about postpartum depression.
AB  - The transition to motherhood in western society is particularly informed by risk
      based scientific and medical discourses and, as a result, women are especially
      subject to rationalities and practices that are employed in the name of risk. The
      aim of this article is to examine the gendered risk discourses that are embedded
      in one aspect of medicalized mothering - the postpartum period. This article
      interrogates three key elements of the discursive construction of postpartum
      depression (PPD) in contemporary psychiatric research literature (approximately
      1980-2007). Specifically, I examine how risk-based reasoning is incorporated into
      the concepts of the postpartum triad and the high-risk mother, and how arguments
      about why PPD is a 'significant social problem' create a tension between the
      rights of the mother and those of the child. By placing women in a position to
      manage certain types of risks related to the postpartum period, these discourses
      serve to responsibilize women and structure their subjectivities in gendered
      ways.This analysis contributes to a growing literature that investigates how
      assumptions about gender, race, class and sexuality are produced and re-produced
      through the notion of risk.

PMID- 20801995
TI  - Being a 'good mother': Dietary governmentality in the family food practices of
      three ethnocultural groups in Canada.
AB  - In this qualitative study with three ethnocultural groups in two regions of
      Canada, we explore how official dietary guidelines provide particular standards
      concerning 'healthy eating' that marginalize other understandings of the
      relationship between food and health. In families where parents and youth held
      shared ways of understanding healthy eating, the role of 'good mother' was
      constructed so as to include healthy eating expertise. Mothers expressed a
      perceived need to be personally responsible for providing skills and knowledge
      about healthy eating as well as guarding children against negative nutritional
      influences. Governing of family eating practices to conform to official
      nutritional advice occurred through information provision, monitoring in shopping
      and meal preparation, restricting and guiding food purchases, and directly
      translating expert knowledges into family food practices. In families where
      parents and youth held differing understandings of healthy eating, primarily
      families from ethnocultural minority groups, mothers often did not employ the
      particular western-originating strategies of conveying healthy eating
      information, or mentoring healthy meal preparation, nor did they regulate or
      restrict children's food consumption. Western dietary guidelines entered into the
      family primarily through the youth, emphasizing the nutritional properties of
      food, often devaluing 'traditional' knowledge about healthy eating. These
      processes exemplify techniques of governmentality which simultaneously exercise
      control over people's behaviour through normalizing some family food practices
      and marginalizing others.

PMID- 20801996
TI  - Cultural brokerage: Creating linkages between voices of lifeworld and medicine in
      cross-cultural clinical settings.
AB  - Culturally competent healthcare has emerged as a policy solution to racial and
      ethnic health disparities in the United States. Current research indicates that
      patient-centered care is a central component of culturally competent healthcare,
      and a rich literature exists on how to elicit patients' lifeworld voices through
      open-ended questions, sensitive communication skills, and power-sharing
      interaction styles. But it remains largely unclear how doctors create linkages
      between cultures of medicine and lifeworld as two sets of incongruent meaning
      systems. Without such linkages, a doctor lacks the cultural tool to incorporate
      her patient's assumptions or frameworks into the voice of medicine, rendering it
      difficult to (at least partially) expand and transform the latter from within.
      This study explores how doctors perform this bridging work, conceptualized as
      cultural brokerage, on the job. Cultural brokerage entails mutual inclusion of
      different sets of schemas or frameworks with which people organize their meanings
      and information. Based on 24 in-depth interviews with primary care physicians in
      Northern California, this study inductively documents four empirical mechanisms
      of cultural brokerage: 'translating between health systems', 'bridging divergent
      images of medicine', 'establishing long-term relationships', and 'working with
      patients' relational networks'. Furthermore, the study argues that cultural
      brokerage must be understood as concrete 'cultural labor', which involves
      specific tasks and requires time and resources. I argue that the performance of
      cultural brokerage work is embedded in the institutional contexts of the clinic
      and therefore faces two macro-level constraints: the cultural ideology and the
      political economy of the American healthcare system.

PMID- 20801997
TI  - Patient resistance towards diagnosis in primary care: Implications for
      concordance.
AB  - This article reports a conversation analytic study of patients' resisting
      responses after doctors' diagnostic statements. In these responses, patients
      bring forward information that confronts the doctor's diagnostic information. We
      examine two turn formats - aligning and misaligning - with which patients
      initiate resistance displays, and describe conversational resources of resistance
      the patients resort to: their immediate symptoms, their past experiences with
      similar illness conditions, information received in past medical visits and their
      diagnostic expectations that have been established earlier in the
      consultation.Through the deployment of these resources, patients orient to the
      doctor's diagnostic information as negotiable and seek to further a shared
      understanding with the doctor on their condition. The results are discussed with
      regard to concordance as a process in which patients and doctors arrive at a
      shared understanding on the nature of the illness and its proper treatment. Our
      analysis illuminates the mechanisms in interaction in and through which
      concordance can be realized. Thus, we suggest that concordance can be seen to
      encompass not only treatment discussion but also the process where participants
      reach agreement about the diagnosis. The data of the study consist of 16
      sequences of patients' resisting responses to diagnosis and is drawn from 86
      Finnish primary care visits for upper respiratory tract infections.

PMID- 20801998
TI  - The logic of identity and resemblance in culturally appropriate health care.
AB  - Greater diversity in the health care workforce is frequently proposed as a means
      of addressing health disparities between minority and majority populations in the
      USA by improving health care access and quality for minority groups. 'Culturally
      appropriate' health care programs that include ethnic resemblance between
      physician and patient are emerging as new technologies of knowledge and power in
      a wide range of health care settings. Based on participant-observation research
      and interviews with patients and health care providers at a federally funded New
      England clinic, this article uses theories of cultural identity supported by
      ethnographic examples to examine arguments in favor of patient-provider
      resemblance. While ethnic identity is often assumed to incorporate cultural
      expertise or competence, in practice, developing and maintaining such expertise
      is the result of repeated performances developed in part through didactic
      trainings described herein. Claims for the efficacy of patient-provider
      resemblance in addressing disparities in quality of care mobilize notions of
      specificity, difference and recognition that both depend on and construct
      racialized ethnic identities. Proposed as a means to expand access to health
      care, resemblance programs nonetheless perpetuate segregation in health care by
      relying on minority health care providers to care for the minority poor. Both
      patients and health care providers I interviewed perceived benefits associated
      with ethnic resemblance, yet also articulated critiques of the essentialized
      notions of identity that render ethnicity automatically efficacious. Following
      Laclau, I argue that an exclusive focus on physician-patient resemblance
      constructs ethnicity as 'mere particularity' and in so doing helps to obscure the
      relations of power and inequality that produce the very health disparities that
      resemblance is meant to solve.

PMID- 20801999
TI  - Septic arthritis in children.

PMID- 20802000
TI  - Evaluating policy and service interventions: framework to guide selection and
      interpretation of study end points.

PMID- 20802001
TI  - Managing gastro-oesophageal reflux in infants.

PMID- 20802002
TI  - Streamlined research governance: are we there yet?
AB  - Despite the promise of a new streamlined process for gaining research ethics and
      governance approval, Nina Fudge, Judith Redfern, Charles Wolfe, and Christopher
      McKevitt argue that the process is still dogged by delay and arbitrary decisions.

PMID- 20802005
TI  - Disease-specific survival in patients with renal cell carcinoma: an audit of a
      large series from Korea.
AB  - BACKGROUND: To evaluate the question of whether or not young age is an
      independent prognostic factor for disease-specific survival in Korean patients
      with renal cell carcinoma. METHODS: A total of 785 patients with an age range of
      22-84 years (median, 56) were included in the study. Patients were categorized
      according to age; 40 years or less (n = 93), 41-60 years (n = 416) and older than
      60 years (n = 276). RESULTS: Patients 40 years or less at diagnosis differed
      significantly from older patients for the following parameters: smaller tumour
      diameter (P = 0.001), less advanced stage (P = 0.002), lower Fuhrman nuclear
      grade (P = 0.017) and fewer clear cell carcinomas (P < 0.001). Five-year disease
      specific survival rate in patients 40 years or younger was also higher than that
      of older patients (92.7% versus 86.0% versus 69.2%; P < 0.001). When subgroup
      analysis was performed, only in patients with tumour diameter 4.1-7.0 cm (P =
      0.018), pT1-pT2,N0,M0 (P = 0.001) or clear cell type carcinoma (P < 0.001),
      disease-specific survival probability for patients 40 years or younger was higher
      than that of older patients. When the Cox proportional hazards model was applied,
      age at diagnosis was not an independent prognostic predictor of disease-specific
      survival. CONCLUSIONS: Tumours found in young adults show more favourable
      histological features than those found in older adults. However, according to
      results from multivariate analysis, young patients do not have higher disease
      specific survival rate after adjusting for clinical and pathological variables.

PMID- 20802006
TI  - A phase II study of cisplatin and irinotecan as induction chemotherapy followed
      by concomitant thoracic radiotherapy with weekly low-dose irinotecan in
      unresectable, stage III, non-small cell lung cancer: JCOG 9706.
AB  - OBJECTIVE: It is important to identify optimal regimens of cisplatin-based, third
      generation chemotherapy and thoracic radiotherapy for patients with unresectable,
      Stage III, non-small cell lung cancer. METHODS: Patients with unresectable, Stage
      III non-small cell lung cancer were treated with the following regimen: cisplatin
      80 mg/m(2) on days 1 and 29, with irinotecan 60 mg/m(2) on days 1, 8, 15, 29, 36,
      and 43 and 30 mg/m(2) on days 57, 64, 71, 78, 85 and 92. Thoracic radiotherapy
      was started on day 57 at 2 Gy/day (total 60 Gy). RESULTS: From February 1998 to
      January 1999, 68 patients were enrolled. Grade 3/4 toxicities during induction
      chemotherapy primarily included neutropenia (73.5%) and diarrhea (20.6%), while
      Grade 3/4 toxicities during concomitant thoracic radiotherapy with irinotecan
      consisted of neutropenia (18.4%), esophagitis (4.1%) and hypoxia (6.5%). There
      was one treatment-related death due to radiation pneumonitis. The response rate
      was 64.7% (95% confidence interval, 52.2-75.9%). The median survival time was
      16.5 (95% confidence interval, 12.6-19.8) months. The 1- and 2 year survival
      rates were 65.8% (95% confidence interval, 54.4-77.1%) and 32.9% (95% confidence
      interval, 21.6-44.1%), respectively. Overall, only 36 (56%) completed both the
      scheduled chemotherapy and thoracic radiotherapy. CONCLUSIONS: Induction
      chemotherapy with cisplatin plus irinotecan followed by low-dose irinotecan and
      concomitant thoracic radiotherapy was feasible according to the prespecified
      decision criteria in this study for patients with unresectable Stage III non
      small cell lung cancer. We did not decide to select this regimen for further
      investigations because approximately half of the patients completed the scheduled
      treatment.

PMID- 20802009
TI  - A patient with severe emphysema and aspiration pneumonia.

PMID- 20802008
TI  - TNF-alpha antagonists beyond approved indications: stories of success and
      prospects for the future.
AB  - Tumour necrosis factor alpha (TNF-alpha) is a key molecule of the inflammatory
      response and data derived from studies in experimental animal models and humans
      suggest that TNF-alpha may be implicated in the pathogenesis of various
      autoimmune and non-infectious inflammatory conditions. Over the past decade
      pharmaceutical agents directed against TNF-alpha (infliximab, adalimumab and
      etanercept) have been widely and successfully employed for the management of
      rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriasis, psoriatic
      arthritis, juvenile idiopathic arthritis and inflammatory bowel disease, whereas
      two novel anti-TNF-alpha agents, golimumab and certolimumab pegol, recently
      entered the market for the treatment of RA, AS, Crohn's disease and psoriasis.
      Encouraged by the positive results obtained from the use of TNF-alpha antagonists
      in terms of efficacy and safety and due to the increasingly accumulating evidence
      regarding the implication of TNF-alpha in the pathogenesis of numerous disorders,
      anti-TNF-alpha agents have been considered for the management of diseases other
      than the ones they were initially approved for. Although in the case of multiple
      sclerosis and chronic heart failure the outcome from the administration of TNF
      alpha blockers had been less than favourable, in other cases of non-infectious
      inflammatory conditions the response to TNF-alpha inhibition had been fairly
      beneficial. More specifically, according to well-documented clinical trials, anti
      TNF-alpha agents exhibited favourable results in Behcet's disease, non-infectious
      ocular inflammation, pyoderma gangrenosum and hidradenitis suppurativa. In this
      review we discuss the successful outcomes as well as the prospects for the future
      from the off-label use of TNF-alpha antagonists.

PMID- 20802010
TI  - Transbronchial needle aspiration: a useful adjunct.

PMID- 20802007
TI  - Environmental factors preceding illness onset differ in phenotypes of the
      juvenile idiopathic inflammatory myopathies.
AB  - OBJECTIVE: To assess whether certain environmental factors temporally associated
      with the onset of juvenile idiopathic inflammatory myopathies (JIIMs) differ
      between phenotypes. METHODS: Physicians completed questionnaires regarding
      documented infections, medications, immunizations and an open-ended question
      about other noted exposures within 6 months before illness onset for 285 patients
      with probable or definite JIIM. Medical records were reviewed for 81% of the
      patients. Phenotypes were defined by standard clinical and laboratory measures.
      RESULTS: Sixty per cent of JIIM patients had a reported exposure within 6 months
      before illness onset. Most patients (62%) had one recorded exposure, 26% had two
      and 12% had three to five exposures. Patients older than the median age at
      diagnosis, those with a longer delay to diagnosis and those with anti-signal
      recognition particle autoantibodies had a higher frequency of documented
      exposures [odds ratios (ORs) 95% CI 3.4, 31]. Infections were the most common
      exposure and represented 44% of the total number of reported exposures. Non
      infectious exposures included medications (18%), immunizations (11%), stressful
      life events (11%) and unusual sun exposure (7%). Exposures varied by age at
      diagnosis, race, disease course and the presence of certain myositis
      autoantibodies. CONCLUSION: The JIIMs may be related to multiple exposures and
      these appear to vary among phenotypes.

PMID- 20802011
TI  - Detailed analysis of health status of Q fever patients 1 year after the first
      Dutch outbreak: a case-control study.
AB  - BACKGROUND: Q fever is a zoonosis caused by the obligate intracellular bacterium
      Coxiella burnetii. The two long-term complications, after primary infection, are
      chronic Q fever in ~1% of patients, and a chronic fatigue syndrome in 10-20%.
      However, the existence of a protracted decreased health status after Q fever
      remains controversial. AIM: To determine the health status of the patients of the
      Q fever outbreak in The Netherlands in 2007, 1 year after primary infection.
      DESIGN: Cross-sectional case-control study. METHODS: Health status of the
      patients from the 2007 Dutch Q fever outbreak was compared to age-, sex- and
      geographically matched and Q fever seronegative controls. Health status of both
      patients and controls was assessed with the Nijmegen Clinical Screening
      Instrument (NCSI). RESULTS: Fifty-four Q fever patients provided 34 years of age-
      and sex-matched controls from the same neighbourhood. Eleven controls had
      positive Q fever serology and were excluded. Q fever patients had significantly
      more problems on the subdomains of symptoms and functional impairment. Overall
      quality of life was decreased in both patients and controls, 59% vs. 39%,
      respectively, ns). Severe fatigue levels were present in 52% of patients vs. 26%
      in controls (P < 0.05). CONCLUSION: These data support a sustained decrease in
      many aspects of health status in Q fever patients in The Netherlands, 1 year
      after primary infection.

PMID- 20802012
TI  - Cardiomyocyte clusters derived from human embryonic stem cells share similarities
      with human heart tissue.
AB  - Cardiotoxicity testing is a key activity in the pharmaceutical industry in order
      to detect detrimental effects of new drugs. A reliable human in vitro model would
      both be beneficial in selection of lead compounds and be important for reducing
      animal experimentation. However, the human heart is a complex organ composed of
      many distinct types of cardiomyocytes, but cardiomyocyte clusters (CMCs) derived
      from human embryonic stem cells could be an option for a cellular model. Data on
      functional properties of CMCs demonstrate similarities to their in vivo analogues
      in human. However, development of an in vitro model requires a more thorough
      comparison of CMCs to human heart tissue. Therefore, we directly compared
      individually isolated CMCs to human fetal, neonatal, adult atrial and ventricular
      heart tissues. Real-time qPCR analysis of mRNA levels and protein staining of ion
      channels and cardiac markers showed in general a similar expression pattern in
      CMCs and human heart. Moreover, a significant decrease in beat frequency was
      noted after addition of Zatebradine, a blocker to I(f) involved in regulation of
      spontaneous contraction in CMCs. The results underscore the similarities of CMCs
      to human cardiac tissue, and further support establishment of novel
      cardiotoxicity assays based on the CMCs in drug discovery.

PMID- 20802014
TI  - British and Polish general practitioners' opinions on the importance of
      preventive medicine.
AB  - The delivery of preventive services in GPs' surgeries falls below recommended
      levels. Different attempts are performed to change the situation. The
      introduction in the UK in 2004 of a new GP contract based on a QOF fundamentally
      changed the way that primary practitioners are paid. Success of this intervention
      caused international interest in using financial incentives as a method of
      improving general practice. Polish primary care is still under development. In
      contemplating reform and the possible introduction of some of these British
      solutions in Poland, it would be valuable to compare what British and Polish GPs'
      think about prevention and see how their opinions can be affected by context in
      which they work. The aim of the survey involving 65 British and 65 Polish GPs was
      to compare what are their views of health promotion. The questionnaire solicited
      information on doctors' demographic characteristics, attitudes toward prevention,
      time they think they spend on preventive procedures and perceptions of the
      importance of 13 selected preventive procedures. Most British and Polish GPs
      answered that prevention is very important and they spend 10-30% of each
      consultation on it. Almost all doctors rated blood pressure measurement as
      important. For British GPs BMI, blood glucose, lipid profile, anti-alcohol and
      anti-smoking advice were important, in contrast to Polish doctors. In the
      presence of clear clinical guidelines, age and gender do not affect doctors'
      opinion on the importance of preventive procedures. Procedures in which GPs are
      directly involved are more important for them.

PMID- 20802013
TI  - Gender-dependent expression of murine Irf5 gene: implications for sex bias in
      autoimmunity.
AB  - Molecular mechanisms that contribute to sex bias in the development of systemic
      lupus erythematosus (SLE), an autoimmune disease, remain unknown. We found that
      the expression levels of interferon regulatory factor 5 (IRF5), a lupus
      susceptibility factor, depend on gender of mice. We found that steady-state
      levels of the Irf5 mRNA were relatively higher in splenic cells from certain
      autoimmune-prone mice (for example, NZB and NZB/W F(1)) than in non-autoimmune
      C57BL/6 mice. Additionally, levels of Irf5 mRNA and protein were higher in
      females than in strain and age-matched males. Accordingly, splenic cells from
      estrogen receptor-alpha (ERalpha) knockout, when compared with the wild-type
      (ERalpha(+/+)), female mice expressed relatively lower levels of Irf5 mRNA and
      the treatment of splenic cells with 17beta-estradiol increased the levels.
      Furthermore, splenic B cells from the female mice had relatively more IRF5
      protein in the nucleus than the male mice. Collectively, our observations
      demonstrate a gender bias in the expression and sub-cellular localization of the
      murine IRF5.

PMID- 20802015
TI  - A marker of homologous recombination predicts pathologic complete response to
      neoadjuvant chemotherapy in primary breast cancer.
AB  - PURPOSE: To assess the prevalence of defective homologous recombination (HR)
      based DNA repair in sporadic primary breast cancers, examine the clincopathologic
      features that correlate with defective HR and the relationship with neoadjuvant
      chemotherapy response. EXPERIMENTAL DESIGN: We examined a cohort of 68 patients
      with sporadic primary breast cancer who received neoadjuvant anthracylcine-based
      chemotherapy, with core biopsies taken 24 hours after the first cycle of
      chemotherapy. We assessed RAD51 focus formation, a marker of HR competence, by
      immunofluorescence in postchemotherapy biopsies along with geminin as a marker of
      proliferative cells. We assessed the RAD51 score as the proportion of
      proliferative cells with RAD51 foci. RESULTS: A low RAD51 score was present in
      26% of cases (15/57, 95% CI: 15%-40%). Low RAD51 score correlated with high
      histologic grade (P = 0.031) and high baseline Ki67 (P = 0.005). Low RAD51 score
      was more frequent in triple-negative breast cancers than in ER- and/or HER2
      positive breast cancer (67% vs. 19% respectively; P = 0.0036). Low RAD51 score
      was strongly predictive of pathologic complete response (pathCR) to chemotherapy,
      with 33% low RAD51 score cancers achieving pathCR compared with 3% of other
      cancers (P = 0.011). CONCLUSIONS: Our results suggest that defective HR, as
      indicated by low RAD51 score, may be one of the factors that underlie sensitivity
      to anthracycline-based chemotherapy. Defective HR is frequent in triple-negative
      breast cancer, but it is also present in a subset of other subtypes, identifying
      breast cancers that may benefit from therapies that target defective HR such as
      PARP inhibitors.

PMID- 20802016
TI  - Radiation-guided drug delivery to mouse models of lung cancer.
AB  - PURPOSE: The purpose of this study was to achieve improved cancer-specific
      delivery and bioavailability of radiation-sensitizing chemotherapy using
      radiation-guided drug delivery. EXPERIMENTAL DESIGN: Phage display technology was
      used to isolate a recombinant peptide (HVGGSSV) that binds to a radiation
      inducible receptor in irradiated tumors. This peptide was used to target nab
      paclitaxel to irradiated tumors, achieving tumor-specificity and enhanced
      bioavailability of paclitaxel. RESULTS: Optical imaging studies showed that
      HVGGSSV-guided nab-paclitaxel selectively targeted irradiated tumors and showed
      1.48 +/- 1.66 photons/s/cm(2)/sr greater radiance compared with SGVSGHV-nab
      paclitaxel, and 1.49 +/- 1.36 photons/s/cm(2)/sr greater than nab-paclitaxel
      alone (P < 0.05). Biodistribution studies showed >5-fold increase in paclitaxel
      levels within irradiated tumors in HVGGSSV-nab-paclitaxel-treated groups as
      compared with either nab-paclitaxel or SGVSGHV-nab-paclitaxel at 72 hours. Both
      Lewis lung carcinoma and H460 lung carcinoma murine models showed significant
      tumor growth delay for HVGGSSV-nab-paclitaxel as compared with nab-paclitaxel,
      SGVSGHV-nab-paclitaxel,and saline controls. HVGGSSV-nab-paclitaxel treatment
      induced a significantly greater loss in vasculature in irradiated tumors compared
      with unirradiated tumors, nab-paclitaxel, SGVSGHV-nab-paclitaxel, and untreated
      controls. CONCLUSIONS: HVGGSSV-nab-paclitaxel was found to bind specifically to
      the tax-interacting protein-1 (TIP-1) receptor expressed in irradiated tumors,
      enhance bioavailability of paclitaxel, and significantly increase tumor growth
      delay as compared with controls in mouse models of lung cancer. Here we show that
      targeting nab-paclitaxel to radiation-inducible TIP-1 results in increased tumor
      specific drug delivery and enhanced biological efficacy in the treatment of
      cancer.

PMID- 20802017
TI  - The basolateral amygdala and nucleus accumbens core mediate dissociable aspects
      of drug memory reconsolidation.
AB  - A distributed limbic-corticostriatal circuitry is implicated in cue-induced drug
      craving and relapse. Exposure to drug-paired cues not only precipitates relapse,
      but also triggers the reactivation and reconsolidation of the cue-drug memory.
      However, the limbic cortical-striatal circuitry underlying drug memory
      reconsolidation is unclear. The aim of this study was to investigate the
      involvement of the nucleus accumbens core and the basolateral amygdala in the
      reconsolidation of a cocaine-conditioned stimulus-evoked memory. Antisense
      oligodeoxynucleotides (ASO) were infused into each structure to knock down the
      expression of the immediate-early gene zif268, which is known to be required for
      memory reconsolidation. Control infusions used missense oligodeoxynucleotides
      (MSO). The effects of zif268 knockdown were measured in two complementary
      paradigms widely used to assess the impact of drug-paired CSs upon drug seeking:
      the acquisition of a new instrumental response with conditioned reinforcement and
      conditioned place preference. The results show that both intranucleus accumbens
      core and intrabasolateral amygdala zif268 ASO infusions at memory reactivation
      impaired the reconsolidation of the memory underlying a cocaine-conditioned place
      preference. However, knockdown of zif268 in the nucleus accumbens at memory
      reactivation had no effect on the memory underlying the conditioned reinforcing
      properties of the cocaine-paired CS measured subsequently, and this is in
      contrast to the marked impairment observed previously following intrabasolateral
      amygdala zif268 ASO infusions. These results suggest that both the basolateral
      amygdala and nucleus accumbens core are key structures within limbic cortical
      striatal circuitry where reconsolidation of a cue-drug memory occurs. However
      reconsolidation of memory representations formed during Pavlovian conditioning
      are differentially localized in each site.

PMID- 20802018
TI  - A novel gene, ROA, is required for normal morphogenesis and discharge of
      ascospores in Gibberella zeae.
AB  - Head blight, caused by Gibberella zeae, is a significant disease among cereal
      crops, including wheat, barley, and rice, due to contamination of grain with
      mycotoxins. G. zeae is spread by ascospores forcibly discharged from sexual
      fruiting bodies forming on crop residues. In this study, we characterized a novel
      gene, ROA, which is required for normal sexual development. Deletion of ROA
      (Deltaroa) resulted in an abnormal size and shape of asci and ascospores but did
      not affect vegetative growth. The Deltaroa mutation triggered round ascospores
      and insufficient cell division after spore delimitation. The asci of the Deltaroa
      strain discharged fewer ascospores from the perithecia but achieved a greater
      dispersal distance than those of the wild-type strain. Turgor pressure within the
      asci was calculated through the analysis of osmolytes in the epiplasmic fluid.
      Deletion of the ROA gene appeared to increase turgor pressure in the mutant asci.
      The higher turgor pressure of the Deltaroa mutant asci and the mutant spore shape
      contributed to the longer distance dispersal. When the Deltaroa mutant was
      outcrossed with a Deltamat1-2 mutant, a strain that contains a green fluorescence
      protein (GFP) marker in place of the MAT1-2 gene, unusual phenotypic segregation
      occurred. The ratio of GFP to non-GFP segregation was 1:1; however, all eight
      spores had the same shape. Taken together, the results of this study suggest that
      ROA plays multiple roles in maintaining the proper morphology and discharge of
      ascospores in G. zeae.

PMID- 20802019
TI  - Associations of cumulative sun exposure and phenotypic characteristics with
      histologic solar elastosis.
AB  - BACKGROUND: Solar elastosis adjacent to melanomas in histologic sections is
      regarded as an indicator of sun exposure, although the associations of UV
      exposure and phenotype with solar elastosis are yet to be fully explored.
      METHODS: The study included 2,589 incident primary melanoma patients with
      assessment of histologic solar elastosis in the population-based Genes,
      Environment, and Melanoma study. Ambient erythemal UV (UVE) at places of
      residence and sun exposure hours, including body site-specific exposure, were
      collected. We examined the association of cumulative site-specific and non-site
      specific sun exposure hours and ambient UVE with solar elastosis in multivariable
      models adjusted for age, sex, center, pigmentary characteristics, nevi, and,
      where relevant, body site. RESULTS: Solar elastosis was associated most strongly
      with site-specific UVE [odds ratio (OR) for top exposure quartile, 5.20; 95%
      confidence interval (95% CI), 3.40-7.96; P for trend <0.001] and also with site
      specific sun exposure (OR for top quartile, 5.12; 95% CI, 3.35-7.83; P for trend
      <0.001). Older age (OR at >70 years, 7.69; 95% CI, 5.14-11.52; P for trend <
      0.001) and having more than 10 back nevi (OR, 0.77; 95% CI, 0.61-0.97; P = 0.03)
      were independently associated with solar elastosis. CONCLUSION: Solar elastosis
      had a strong association with higher site-specific UVE dose, older age, and fewer
      nevi. IMPACT: Solar elastosis could be a useful biomarker of lifetime site
      specific UV. Future research is needed to explore whether age represents more
      than simple accumulation of sun exposure and to determine why people with more
      nevi may be less prone to solar elastosis.

PMID- 20802020
TI  - Reproductive factors and exogenous hormone use in relation to risk of glioma and
      meningioma in a large European cohort study.
AB  - BACKGROUND: The etiologies of glioma and meningioma tumors are largely unknown.
      Although reproductive hormones are thought to influence the risk of these tumors,
      epidemiologic data are not supportive of this hypothesis; however, few cohort
      studies have published on this topic. We examined the relation between
      reproductive factors and the risk of glioma and meningioma among women in the
      European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS:
      After a mean of 8.4 years of follow-up, 193 glioma and 194 meningioma cases were
      identified among 276,212 women. Information on reproductive factors and hormone
      use was collected at baseline. Cox proportional hazard regression was used to
      determine hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS: No
      associations were observed between glioma or meningioma risk and reproductive
      factors, including age at menarche, parity, age at first birth, menopausal
      status, and age at menopause. A higher risk of meningioma was observed among
      postmenopausal women who were current users of hormone replacement therapy (HR,
      1.79; 95% CI, 1.18-2.71) compared with never users. Similarly, current users of
      oral contraceptives were at higher risk of meningioma than never users (HR, 3.61;
      95% CI, 1.75-7.46). CONCLUSION: Our results do not support a role for estrogens
      and glioma risk. Use of exogenous hormones, especially current use, seems to
      increase meningioma risk. However, these findings could be due to diagnostic bias
      and require confirmation. IMPACT: Elucidating the role of hormones in brain tumor
      development has important implications and needs to be further examined using
      biological measurements.

PMID- 20802021
TI  - Oral contraceptive use and breast cancer: a prospective study of young women.
AB  - BACKGROUND: Previous studies convincingly showed an increase in risk of breast
      cancer associated with current or recent use of oral contraceptives from the
      1960s to 1980s. The relation of contemporary oral contraceptive formulations to
      breast cancer risk is less clear. METHODS: We assessed lifetime oral
      contraceptive use and the specific formulations used among 116,608 female nurses
      ages 25 to 42 years at enrollment in 1989, and subsequently updated this
      information every 2 years. We related this information to risk of breast cancer
      up to June 1, 2001. RESULTS: During 1,246,967 person-years of follow-up, 1,344
      cases of invasive breast cancer were diagnosed. Past use of any oral
      contraceptive was not related to breast cancer risk [multivariate relative risk
      (RR), 1.12; 95% confidence interval 0.95-1.33]. Current use of any oral
      contraceptive was related to a marginally significant higher risk (multivariate
      RR, 1.33; 95% CI, 1.03-1.73). One specific formulation substantially accounted
      for the excess risk: the RR for current use of triphasic preparations with
      levonorgestrel as the progestin was 3.05 (95% CI, 2.00-4.66; P < 0.0001).
      CONCLUSIONS: Current use of oral contraceptives carries an excess risk of breast
      cancer. Levonorgestrel used in triphasic preparations may account for much of
      this elevation in risk. IMPACT: Different oral contraceptive formulations might
      convey different risks of breast cancer; ongoing monitoring of these associations
      is necessary as oral contraceptive formulations change.

PMID- 20802022
TI  - Identification of a novel biomarker, SEMA5A, for non-small cell lung carcinoma in
      nonsmoking women.
AB  - BACKGROUND: Although cigarette smoking is the major risk factor for lung cancer,
      only 7% of female lung cancer patients in Taiwan have a history of smoking. The
      genetic mechanisms of carcinogenesis in nonsmokers are unclear, but semaphorins
      have been suggested to play a role as lung tumor suppressors. This report is a
      comprehensive analysis of the molecular signature of nonsmoking female lung
      cancer patients in Taiwan, with a particular focus on the semaphorin gene family.
      METHODS: Sixty pairs of tumor and adjacent normal lung tissue specimens were
      analyzed by using Affymetrix U133plus2.0 expression arrays. Differentially
      expressed genes in tumor tissues were identified by a paired t test and validated
      by reverse transcriptase-PCR and immunohistochemistry. Functional analysis was
      conducted by using Ingenuity Pathway Analysis as well as gene set enrichment
      analysis and sigPathway algorithms. Kaplan-Meier survival analyses were used to
      evaluate the association of SEMA5A expression and clinical outcome. RESULTS: We
      identified 687 differentially expressed genes in non-small cell lung carcinoma
      (NSCLC). Many of these genes, most notably the semaphorin family, were
      participants in the axon guidance signaling pathway. The downregulation of SEMA5A
      in tumor tissue, both at the transcriptional and translational levels, was
      associated with poor survival among nonsmoking women with NSCLC. CONCLUSIONS: In
      summary, several semaphorin gene family members were identified as potential
      therapeutic targets, and SEMA5A may be useful as a prognostic biomarker for
      NSCLC, which may also be gender specific in Taiwanese patients. IMPACT: A novel
      biomarker for NSCLC is identified.

PMID- 20802023
TI  - Complement factor H is elevated in bronchoalveolar lavage fluid and sputum from
      patients with lung cancer.
AB  - BACKGROUND: Cytologic examination of specimens obtained from the respiratory
      tract is a lung cancer diagnostic procedure with high specificity but moderate
      sensitivity. The use of molecular biomarkers may enhance the sensitivity of
      cytologic examination in the detection of lung cancer. METHODS: Complement factor
      H, a protein secreted by lung cancer cells, was quantified in a series of
      bronchoalveolar lavage supernatants from lung cancer patients and patients with
      nonmalignant respiratory diseases. Albumin, total protein content, and hemoglobin
      were also analyzed. Results were validated in independent sets of bronchoalveolar
      lavage and sputum supernatants. RESULTS: There was a significantly higher
      concentration of factor H in bronchoalveolar lavage samples from lung cancer
      patients. The sensitivity and specificity of the factor H test was 82% and 77%,
      respectively. These results were validated in an independent set of patients with
      nearly identical results. Furthermore, 70% and 45% of bronchoalveolar lavage
      fluids from central and peripheral tumors, respectively, reported as
      cytologically negative, were classified as positive using this marker. Finally,
      the test was evaluated in a series of sputum supernatants from lung cancer
      patients and controls. The sensitivity and specificity of the factor H test in
      this series was 80% and 88%, respectively. CONCLUSION: Factor H is elevated in
      bronchoalveolar lavage and sputum from lung cancer patients. IMPACT: Measurement
      of molecular biomarkers, such as complement factor H, may be used in the future
      as an adjunct to cytology in the diagnosis of malignant pulmonary diseases.

PMID- 20802024
TI  - Complex karyotype newly defined: the strongest prognostic factor in advanced
      childhood myelodysplastic syndrome.
AB  - To identify cytogenetic risk factors predicting outcome in children with advanced
      myelodysplastic syndrome, overall survival of 192 children prospectively enrolled
      in European Working Group of Myelodysplastic Syndrome in Childhood studies was
      evaluated with regard to karyotypic complexity. Structurally complex constitutes
      a new definition of complex karyotype characterized by more than or equal to 3
      chromosomal aberrations, including at least one structural aberration. Five-year
      overall survival in patients with more than or equal to 3 clonal aberrations,
      which were not structurally complex, did not differ from that observed in
      patients with normal karyotype. Cox regression analysis revealed the presence of
      a monosomal and structurally complex karyotype to be strongly associated with
      poor prognosis (hazard ratio = 4.6, P < .01). Notably, a structurally complex
      karyotype without a monosomy was associated with a very short 2-year overall
      survival probability of only 14% (hazard ratio = 14.5; P < .01). The presence of
      a structurally complex karyotype was the strongest independent prognostic marker
      predicting poor outcome in children with advanced myelodysplastic syndrome.

PMID- 20802025
TI  - Genome-wide association study identifies novel loci for plasma levels of protein
      C: the ARIC study.
AB  - Protein C is an important endogenous anticoagulant in hemostasis. Deficiencies of
      protein C due to genetic mutations or a low level of circulating protein C
      increase the risk of venous thromboembolism. We performed a genome-wide
      association scan for plasma protein C antigen concentration with approximately
      2.5 million single-nucleotide polymorphisms in 8048 individuals of European
      ancestry and a replication analysis in a separate sample of 1376 individuals in
      the Atherosclerosis Risk in Communities Study. Four independent loci from 3
      regions were identified with genome-wide significance: 2p23 (GCKR, best SNP
      rs1260326, P = 2.04 * 10(-17)), 2q13-q14 (PROC, rs1158867, P = 3.77 * 10(-36)),
      20q11 (near and within PROCR, rs8119351, P = 2.68 * 10(-203)), and 20q11.22
      (EDEM2, rs6120849, P = 7.19 * 10(-37) and 5.23 * 10(-17) before and after
      conditional analysis, respectively). All 4 loci replicated in the independent
      sample. Furthermore, pooling the discovery and replication sets yielded an
      additional locus at chromosome 7q11.23 (BAZ1B, rs17145713, P = 2.83 * 10(-8)).
      The regions marked by GCKR, EDEM2, and BAZ1B are novel loci that have not been
      previously reported for association with protein C concentration. In summary,
      this first genome-wide scan for circulating protein C concentration identified
      both new and known loci in the general population. These findings may improve the
      understanding of physiologic mechanisms in protein C regulation.

PMID- 20802027
TI  - Rest tremor in advanced essential tremor: a post-mortem study of nine cases.
AB  - BACKGROUND: Rest tremor may occur in as many as 30% of essential tremor (ET)
      patients. It is not clear whether this tremor is a sentinel marker for brainstem
      Lewy body pathology. Here we report the clinical and post-mortem findings of nine
      ET cases with upper-extremity rest tremor in the absence of other parkinsonian
      features. METHODS: All brains had a complete neuropathological assessment. Tissue
      sections from the brainstem and basal ganglia were immunostained with alpha
      synuclein antibody. RESULTS: All cases had longstanding ET (median duration=42
      years) with moderate to severe arm tremor. Rest tremor involved both arms in
      seven (77.8%) cases and one arm in two cases. The rest tremor score was
      correlated with the total action tremor score (r=0.69, p=0.04). The number of
      torpedoes was elevated, and Purkinje cells, reduced. Post-mortem changes in the
      substantia nigra pars compacta (SNc), caudate, putamen and globus pallidum were
      minimal, and neither Lewy bodies nor Lewy neurites were evident. CONCLUSIONS: In
      nine ET brains with upper-extremity rest tremor, neither Lewy body-containing
      neurons nor Lewy neurites were found on alpha-synuclein immunostained sections,
      and other pathological changes in the basal ganglia were minimal. These data
      support the notion that isolated rest tremor in longstanding ET is not the
      expression of underlying Lewy body pathology in the SNc.

PMID- 20802026
TI  - Loss of basic lexical knowledge in old age.
AB  - BACKGROUND: Basic lexical skills are hypothesised to be relatively preserved in
      mild dementia, but clinical studies have reported inconsistent results. METHODS:
      More than 400 older Catholic nuns, priests and brothers recruited from groups
      across the USA completed annual evaluations for up to 15 years, died and
      underwent brain autopsy. Each clinical evaluation included administration of a 20
      item word reading test and a 15-item vocabulary test, which were combined to form
      a composite measure of word knowledge. In a uniform neuropathological
      examination, Alzheimer's disease pathology was quantified with a composite index
      of plaques and tangles, and the presence of gross and microscopic cerebral
      infarctions and Lewy bodies was recorded. RESULTS: The post-mortem level of
      Alzheimer's disease neuropathology was linearly related to rate of decline in
      word knowledge. Decline was nearly fourfold faster at a relatively high level of
      pathology (75th percentile) compared with a relatively low level (25th
      percentile). Neocortical (but not nigral or limbic) Lewy bodies and gross (but
      not microscopic) cerebral infarction were also associated with a more rapid
      decline in word knowledge. Effects for word reading and vocabulary were similar,
      except that gross cerebral infarction was associated with accelerated decline in
      vocabulary, but not in word reading. CONCLUSION: Common neuropathological changes
      associated with late-life dementia impair word knowledge in old age, calling into
      question the use of word knowledge tests to estimate premorbid cognitive ability.

PMID- 20802028
TI  - Stunned brain syndrome: serial diffusion perfusion MRI of delayed recovery
      following revascularisation for acute ischaemic stroke.
AB  - BACKGROUND: Clinical response immediately after revascularisation therapy differs
      among patients. Although reperfusion is the deciding factor with respect to this
      dramatic response to revascularisation therapy, the influence of pre- and post
      treatment diffusion-perfusion status on the speed and degree of recovery are
      unknown. METHODS: Consecutive stroke patients who were eligible for
      revascularisation therapy underwent serial diffusion-perfusion MRI. Tmax
      perfusion maps were generated, and stroke severity and recovery were assessed up
      to day 90. The relationship of diffusion and perfusion lesion indices with the
      speed and degree of recovery were evaluated. RESULTS: 69 patients (42 men; aged
      66.3+/-15.9 years) were included; National Institutes of Health Stroke Scale
      (NIHSS) score was 13.3+/-6.4 points. 19 received intravenous tissue plasminogen
      activator (tPA) and 50 received endovascular therapy with/without intravenous
      tPA. Early dramatic improvement (NIHSS score reduction of >=40% within 24 h) was
      observed in 24 (34.8%) patients. Among the other 45 patients, 18 (40%) showed
      good outcomes (modified Rankin score 0-2 at day 90), suggesting delayed recovery.
      The volume of post-treatment perfusion delay was similar between the early and
      delayed recovery groups (p=0.329) but smaller than in the non-responders group
      (p<0.05). Multivariate testing revealed that smaller post-treatment perfusion
      delay volumes were independently associated with both early dramatic improvement
      and delayed recovery. In addition, initial diffusion weighted imaging lesion
      volume was smaller in the former than in the latter (p=0.029) and was
      independently associated with early dramatic recovery. CONCLUSIONS: A significant
      proportion of patients with a lack of early dramatic improvement (40%) showed
      delayed recovery. Both pretreatment infarct volume and post-treatment reperfusion
      correlated with the degree and speed of recovery.

PMID- 20802029
TI  - How long can you keep working with benign multiple sclerosis?
AB  - OBJECTIVE: To study employment in benign multiple sclerosis (MS), the frequency
      of employment was analysed and the effect of early clinical and demographic
      factors on time to disability pension was evaluated in a population based MS
      cohort. The frequency of depression, cognitive function, fatigue and pain between
      benign and non-benign MS patients was compared, and their impact on employment in
      benign MS was studied. METHODS: All 188 patients alive, including 60 benign
      patients with onset of MS during 1976-1986 in Hordaland County, Western Norway,
      were interviewed and clinically examined in 2003. The Expanded Disability Status
      Scale (EDSS), depression (Beck Depression Inventory), cognitive function,
      fatigue, pain, year of disability pension, employment and type of occupation were
      registered. Benign MS was defined as an EDSS score <=3.0 at least 10 years after
      disease onset. RESULTS: After a mean disease duration of 22.2 years, 32.4% of the
      cohort were still employed. A relapsing-remitting course, higher educational
      level and light physical work were significantly associated with longer time to
      disability pension in the general MS population. Thirty-nine (65.0%) benign MS
      patients were employed, independent of light or heavy physical work. Mild
      depressive symptoms were markedly associated with not being employed in benign MS
      (OR=7.3). CONCLUSIONS: A relapsing-remitting course, higher educational level and
      light physical work significantly predicted longer time to disability pension in
      the total MS population. Among the benign MS patients, depressive symptoms,
      although mild, were strongly associated with not being employed.

PMID- 20802030
TI  - Posterior versus anterior circulation strokes: comparison of clinical,
      radiological and outcome characteristics.
AB  - BACKGROUND AND PURPOSE: Physicians treating patients with posterior circulation
      strokes (PCS) tended to debate more on whether or not to introduce
      anticoagulation rather than performing investigations to identify stroke
      aetiology, as in patients with anterior circulation strokes (ACS). Recent
      findings suggest that stroke aetiologies of PCS and ACS are more alike than
      dissimilar, suggesting that PCS deserve the same investigations as ACS. The
      characteristics and current diagnostic evaluation between patients with PCS and
      ACS were compared. METHODS: 312 consecutive patients with first ever ACS and 93
      patients with first ever PCS were prospectively analysed. RESULTS: Patients with
      ACS and PCS did not differ in terms of demographic characteristics, prevalence of
      vascular risk factors, diagnostic evaluation or stroke aetiology. The median
      National Institutes of Health Stroke Scale score was 8 in ACS and 4 in PCS
      (p=0.004). Brain imaging revealed more often pathological findings in ACS than
      PCS. The proportion of non-thrombolysed patients with a favourable clinical
      outcome (modified Rankin score 0-2) was similar in ACS and PCS (67.0% vs 78.4%;
      p=0.08). In non-thrombolysed patients, stroke severity was an independent
      predictor of clinical outcome both in ACS (OR 1.60, 95% CI 1.2 to 2.1; p<0.0001)
      and in PCS (OR 1.22, 95% CI 1.03 to 1.44; p=0.02) while age predicted poor
      outcome only in ACS (OR 1.11, 95% CI 1.01 to 1.22; p=0.007). In thrombolysed
      patients, stroke severity was the only outcome predictor in ACS (OR 1.14, 95% CI
      1.04 to 1.25; p=0.004) while we identified no statistically relevant predictor of
      PCS outcome. CONCLUSIONS: In PCS and ACS, baseline variables, aetiology and
      outcome are more alike than different.

PMID- 20802031
TI  - Increased number of heterotopic Purkinje cells in essential tremor.
AB  - OBJECTIVE: Recent postmortem studies reveal degenerative changes, including
      Purkinje cell (PC) loss, in most brains from individuals with essential tremor
      (ET). Heterotopic PCs (HPCs) (ie, PC bodies displaced into the molecular layer)
      may be found in neurodegenerative diseases with PC loss. HPCs have been observed
      in ET but no quantitative case control analysis has been performed. METHODS: HPCs
      were counted in 35 ET brains and 32 control brains (including 21 non-diseased
      controls and 11 diseased controls with progressive supranuclear palsy (PSP))
      using a standard 20 * 25 mm cerebellar cortical section stained with a modified
      Bielscholwsky method. RESULTS: The median number of HPCs per section was three
      times higher in 35 ET cases (median 3, mean +/- SD 3.8 +/- 3.6, range 0-14)
      versus 32 controls (median 1, mean +/- SD 1.6 +/- 1.7, range 0-5) (p = 0.007).
      The number of HPCs was similarly low in the 21 non-diseased controls and 12 PSP
      brains (median 1 in each group) (p = 0.04 and p = 0.01 compared with ET). In ET,
      the number of HPCs was inversely related to the number of PCs (Spearman's rho 
      0.36, p = 0.038) (ie, cases with more HPCs had fewer PCs). CONCLUSION: PC
      heterotopia, which occurs in cerebellar degenerative disorders, is also a feature
      of ET. These findings further contribute to our understanding of the postmortem
      changes in this common neurological disease.

PMID- 20802032
TI  - Complete genome sequence of Mycoplasma hyorhinis strain HUB-1.
AB  - Mycoplasma hyorhinis is generally considered a swine pathogen yet is most
      commonly found infecting laboratory cell lines. An increasing body of evidence
      suggests that chronic infections with M. hyorhinis may cause oncogenic
      transformation. Here, we announce the complete genome sequence of M. hyorhinis
      strain HUB-1.

PMID- 20802033
TI  - A periplasmic LolA derivative with a lethal disulfide bond activates the Cpx
      stress response system.
AB  - LolA accommodates the acyl chains of lipoproteins in its hydrophobic cavity and
      shuttles between the inner and outer membranes through the hydrophilic periplasm
      to place lipoproteins in the outer membrane. The LolA(I93C/F140C) derivative, in
      which Cys replaces Ile at position 93 and Phe at position 140, strongly inhibited
      growth in the absence of a reducing agent because of the lethal intramolecular
      disulfide bond between the two Cys residues. Expression of I93C/F140C was found
      to activate the Cpx two-component system, which responds to cell envelope stress.
      The inhibition of growth by I93C/F140C was partly suppressed by overproduction of
      LolCDE, which is an ATP-binding cassette transporter and mediates the transfer of
      lipoproteins from the inner membrane to LolA. A substantial portion of the
      oxidized form, but not the reduced one, of I93C/F140C expressed on LolCDE
      overproduction was recovered in the membrane fraction, whereas wild-type LolA was
      localized in the periplasm even when LolCDE was overproduced. Moreover, LolCDE
      overproduction stabilized I93C/F140C and therefore caused an increase in its
      level. Taken together, these results indicate that oxidized I93C/F140C stably
      binds to LolCDE, which causes strong envelope stress.

PMID- 20802034
TI  - Radiation desiccation response motif-like sequences are involved in
      transcriptional activation of the Deinococcal ssb gene by ionizing radiation but
      not by desiccation.
AB  - Single-stranded-DNA binding protein (SSB) levels during poststress recovery of
      Deinococcus radiodurans were significantly enhanced by (60)Co gamma rays or
      mitomycin C treatment but not by exposure to UV rays, hydrogen peroxide (H2O2),
      or desiccation. Addition of rifampin prior to postirradiation recovery blocked
      such induction. In silico analysis of the ssb promoter region revealed a 17-bp
      palindromic radiation/desiccation response motif (RDRM1) at bp -114 to -98 and a
      somewhat similar sequence (RDRM2) at bp -213 to -197, upstream of the ssb open
      reading frame. Involvement of these cis elements in radiation-responsive ssb gene
      expression was assessed by constructing transcriptional fusions of edited
      versions of the ssb promoter region with a nonspecific acid phosphatase encoding
      reporter gene, phoN. Recombinant D. radiodurans strains carrying such constructs
      clearly revealed (i) transcriptional induction of the ssb promoter upon
      irradiation and mitomycin C treatment but not upon UV or H2O2 treatment and (ii)
      involvement of both RDRM-like sequences in such activation of SSB expression, in
      an additive manner.

PMID- 20802035
TI  - A commensal gone bad: complete genome sequence of the prototypical
      enterotoxigenic Escherichia coli strain H10407.
AB  - In most cases, Escherichia coli exists as a harmless commensal organism, but it
      may on occasion cause intestinal and/or extraintestinal disease. Enterotoxigenic
      E. coli (ETEC) is the predominant cause of E. coli-mediated diarrhea in the
      developing world and is responsible for a significant portion of pediatric
      deaths. In this study, we determined the complete genomic sequence of E. coli
      H10407, a prototypical strain of enterotoxigenic E. coli, which reproducibly
      elicits diarrhea in human volunteer studies. We performed genomic and
      phylogenetic comparisons with other E. coli strains, revealing that the
      chromosome is closely related to that of the nonpathogenic commensal strain E.
      coli HS and to those of the laboratory strains E. coli K-12 and C. Furthermore,
      these analyses demonstrated that there were no chromosomally encoded factors
      unique to any sequenced ETEC strains. Comparison of the E. coli H10407 plasmids
      with those from several ETEC strains revealed that the plasmids had a mosaic
      structure but that several loci were conserved among ETEC strains. This study
      provides a genetic context for the vast amount of experimental and
      epidemiological data that have been published.

PMID- 20802036
TI  - Comparative analysis of the biochemical and functional properties of C-terminal
      domains of autotransporters.
AB  - Autotransporters (ATs) are the largest group of proteins secreted by Gram
      negative bacteria and include many virulence factors from human pathogens. ATs
      are synthesized as large precursors with a C-terminal domain that is inserted in
      the outer membrane (OM) and is essential for the translocation of an N-terminal
      passenger domain to the extracellular milieu. Several mechanisms have been
      proposed for AT secretion. Self-translocation models suggest transport across a
      hydrophilic channel formed by an internal pore of the beta-barrel or by the
      oligomerization of C-terminal domains. Alternatively, an assisted-translocation
      model suggests that transport employs a conserved machinery of the bacterial OM
      such as the Bam complex. In this work we have investigated AT secretion by
      carrying out a comparative study to analyze the conserved biochemical and
      functional features of different C-terminal domains selected from ATs of
      gammaproteobacteria, betaproteobacteria, alphaproteobacteria, and
      epsilonproteobacteria. Our results indicate that C-terminal domains having an N
      terminal alpha-helix and a beta-barrel constitute functional transport units for
      the translocation of peptides and immunoglobulin domains with disulfide bonds. In
      vivo and in vitro analyses show that multimerization is not a conserved feature
      in AT C-terminal domains. Furthermore, we demonstrate that the deletion of the
      conserved alpha-helix severely impairs beta-barrel folding and OM insertion and
      thereby blocks passenger domain secretion. These observations suggest that the AT
      beta-barrel without its alpha-helix cannot form a stable hydrophilic channel in
      the OM for protein translocation. The implications of our data for an
      understanding of AT secretion are discussed.

PMID- 20802037
TI  - A novel six-rhodopsin system in a single archaeon.
AB  - Microbial rhodopsins, a diverse group of photoactive proteins found in Archaea,
      Bacteria, and Eukarya, function in photosensing and photoenergy harvesting and
      may have been present in the resource-limited early global environment. Four
      different physiological functions have been identified and characterized for
      nearly 5,000 retinal-binding photoreceptors, these being ion transporters that
      transport proton or chloride and sensory rhodopsins that mediate light-attractant
      and/or -repellent responses. The greatest number of rhodopsins previously
      observed in a single archaeon had been four. Here, we report a newly discovered
      six-rhodopsin system in a single archaeon, Haloarcula marismortui, which shows a
      more diverse absorbance spectral distribution than any previously known rhodopsin
      system, and, for the first time, two light-driven proton transporters that
      respond to the same wavelength. All six rhodopsins, the greatest number ever
      identified in a single archaeon, were first shown to be expressed in H.
      marismortui, and these were then overexpressed in Escherichia coli. The proteins
      were purified for absorption spectra and photocycle determination, followed by
      measurement of ion transportation and phototaxis. The results clearly indicate
      the existence of a proton transporter system with two isochromatic rhodopsins and
      a new type of sensory rhodopsin-like transducer in H. marismortui.

PMID- 20802038
TI  - Mechanism of positive regulation by DsrA and RprA small noncoding RNAs: pairing
      increases translation and protects rpoS mRNA from degradation.
AB  - Small noncoding RNAs (sRNAs) regulate gene expression in Escherichia coli by base
      pairing with mRNAs and modulating translation and mRNA stability. The sRNAs DsrA
      and RprA stimulate the translation of the stress response transcription factor
      RpoS by base pairing with the 5' untranslated region of the rpoS mRNA. In the
      present study, we found that the rpoS mRNA was unstable in the absence of DsrA
      and RprA and that expression of these sRNAs increased both the accumulation and
      the half-life of the rpoS mRNA. Mutations in dsrA, rprA, or rpoS that disrupt the
      predicted pairing sequences and reduce translation of RpoS also destabilize the
      rpoS mRNA. We found that the rpoS mRNA accumulates in an RNase E mutant strain in
      the absence of sRNA expression and, therefore, is degraded by an RNase E-mediated
      mechanism. DsrA expression is required, however, for maximal translation even
      when rpoS mRNA is abundant. This suggests that DsrA protects rpoS mRNA from
      degradation by RNase E and that DsrA has a further activity in stimulating RpoS
      protein synthesis. rpoS mRNA is subject to degradation by an additional pathway,
      mediated by RNase III, which, in contrast to the RNase E-mediated pathway, occurs
      in the presence and absence of DsrA or RprA. rpoS mRNA and RpoS protein levels
      are increased in an RNase III mutant strain with or without the sRNAs, suggesting
      that the role of RNase III in this context is to reduce the translation of RpoS
      even when the sRNAs are acting to stimulate translation.

PMID- 20802039
TI  - AglJ adds the first sugar of the N-linked pentasaccharide decorating the
      Haloferax volcanii S-layer glycoprotein.
AB  - Like the Eukarya and Bacteria, the Archaea also perform N glycosylation. Using
      the haloarchaeon Haloferax volcanii as a model system, a series of Agl proteins
      involved in the archaeal version of this posttranslational modification has been
      identified. In the present study, the participation of HVO_1517 in N
      glycosylation was considered, given its homology to a known component of the
      eukaryal N-glycosylation pathway and because of the genomic proximity of HVO_1517
      to agl genes encoding known elements of the H. volcanii N-glycosylation process.
      By combining the deletion of HVO_1517 with mass spectrometric analysis of both
      dolichol phosphate monosaccharide-charged carriers and the S-layer glycoprotein,
      evidence was obtained showing the participation of HVO_1517, renamed AglJ, in
      adding the first hexose of the N-linked pentasaccharide decorating this reporter
      glycoprotein. The deletion of aglJ, however, did not fully prevent the attachment
      of a hexose residue to the S-layer glycoprotein. Moreover, in the absence of
      AglJ, the level of only one of the three monosaccharide-charged dolichol
      phosphate carriers detected in the cell was reduced. Nonetheless, in cells
      lacking AglJ, no further sugar subunits were added to the remaining
      monosaccharide-charged dolichol phosphate carriers or to the monosaccharide
      modified S-layer glycoprotein, pointing to the importance of the sugar added
      through the actions of AglJ for proper N glycosylation. Finally, while aglJ can
      be deleted, H. volcanii surface layer integrity is compromised in the absence of
      the encoded protein.

PMID- 20802040
TI  - Biosynthetic pathway for gamma-cyclic sarcinaxanthin in Micrococcus luteus:
      heterologous expression and evidence for diverse and multiple catalytic functions
      of C(50) carotenoid cyclases.
AB  - We report the cloning and characterization of the biosynthetic gene cluster
      (crtE, crtB, crtI, crtE2, crtYg, crtYh, and crtX) of the gamma-cyclic C(50)
      carotenoid sarcinaxanthin in Micrococcus luteus NCTC2665. Expression of the
      complete and partial gene cluster in Escherichia coli hosts revealed that
      sarcinaxanthin biosynthesis from the precursor molecule farnesyl pyrophosphate
      (FPP) proceeds via C(40) lycopene, C(45) nonaflavuxanthin, C(50) flavuxanthin,
      and C(50) sarcinaxanthin. Glucosylation of sarcinaxanthin was accomplished by the
      crtX gene product. This is the first report describing the biosynthetic pathway
      of a gamma-cyclic C(50) carotenoid. Expression of the corresponding genes from
      the marine M. luteus isolate Otnes7 in a lycopene-producing E. coli host resulted
      in the production of up to 2.5 mg/g cell dry weight sarcinaxanthin in shake
      flasks. In an attempt to experimentally understand the specific difference
      between the biosynthetic pathways of sarcinaxanthin and the structurally related
      epsilon-cyclic decaprenoxanthin, we constructed a hybrid gene cluster with the
      gamma-cyclic C(50) carotenoid cyclase genes crtYg and crtYh from M. luteus
      replaced with the analogous epsilon-cyclic C(50) carotenoid cyclase genes crtYe
      and crtYf from the natural decaprenoxanthin producer Corynebacterium glutamicum.
      Surprisingly, expression of this hybrid gene cluster in an E. coli host resulted
      in accumulation of not only decaprenoxanthin, but also sarcinaxanthin and the
      asymmetric epsilon- and gamma-cyclic C(50) carotenoid sarprenoxanthin, described
      for the first time in this work. Together, these data contributed to new insight
      into the diverse and multiple functions of bacterial C(50) carotenoid cyclases as
      key catalysts for the synthesis of structurally different carotenoids.

PMID- 20802041
TI  - The elemental sulfur-responsive protein (SipA) from the hyperthermophilic
      archaeon Pyrococcus furiosus is regulated by sulfide in an iron-dependent manner.
AB  - The gene (sipA) encoding the sulfur-induced protein A (PF2025) is highly
      upregulated during growth of Pyrococcus furiosus on elemental sulfur (S(0)).
      Expression of sipA is regulated by sulfide, the product of S(0) reduction, but in
      an iron-dependent manner. SipA is proposed to play a role in intracellular iron
      sulfide detoxification.

PMID- 20802042
TI  - Molecular and catalytic properties of the aldehyde dehydrogenase of
      Gluconacetobacter diazotrophicus, a quinoheme protein containing pyrroloquinoline
      quinone, cytochrome b, and cytochrome c.
AB  - Several aldehyde dehydrogenase (ALDH) complexes have been purified from the
      membranes of acetic acid bacteria. The enzyme structures and the chemical nature
      of the prosthetic groups associated with these enzymes remain a matter of debate.
      We report here on the molecular and catalytic properties of the membrane-bound
      ALDH complex of the diazotrophic bacterium Gluconacetobacter diazotrophicus. The
      purified ALDH complex is a heterodimer comprising two subunits of 79.7 and 50
      kDa, respectively. Reversed-phase high-pressure liquid chromatography (HPLC) and
      electron paramagnetic resonance spectroscopy led us to demonstrate, for the first
      time, the unequivocal presence of a pyrroloquinoline quinone prosthetic group
      associated with an ALDH complex from acetic acid bacteria. In addition, heme b
      was detected by UV-visible light (UV-Vis) spectroscopy and confirmed by reversed
      phase HPLC. The smaller subunit bears three cytochromes c. Aliphatic aldehydes,
      but not formaldehyde, were suitable substrates. Using ferricyanide as an electron
      acceptor, the enzyme showed an optimum pH of 3.5 that shifted to pH 7.0 when
      phenazine methosulfate plus 2,6-dichlorophenolindophenol were the electron
      acceptors. Acetaldehyde did not reduce measurable levels of the cytochrome b and
      c centers; however, the dithionite-reduced hemes were conveniently oxidized by
      ubiquinone-1; this finding suggests that cytochrome b and the cytochromes c
      constitute an intramolecular redox sequence that delivers electrons to the
      membrane ubiquinone.

PMID- 20802044
TI  - Loss of compartmentalization of sigma(E) activity need not prevent formation of
      spores by Bacillus subtilis.
AB  - Compartmentalization of the activities of RNA polymerase sigma factors is a
      hallmark of formation of spores by Bacillus subtilis. It is initiated soon after
      the asymmetrically located sporulation division takes place with the activation
      of sigma(F) in the smaller cell, the prespore. sigma(F) then directs a signal via
      the membrane protease SpoIIGA to activate sigma(E) in the larger mother cell by
      processing of pro-sigma(E). Here, we show that sigma(E) can be activated in the
      prespore with little effect on sporulation efficiency, implying that complete
      compartmentalization of sigma(E) activity is not essential for spore formation.
      sigma(E) activity in the prespore can be obtained by inducing transcription in
      the prespore of spoIIGA or of sigE*, which encodes a constitutively active form
      of sigma(E), but not of spoIIGB, which encodes pro-sigma(E). We infer that
      sigma(E) compartmentalization is partially attributed to a competition between
      the compartments for the activation signaling protein SpoIIR. Normally, SpoIIGA
      is predominantly located in the mother cell and as a consequence confines
      sigma(E) activation to it. In addition, we find that CsfB, previously shown to
      inhibit sigma(G), is independently inhibiting sigma(E) activity in the prespore.
      CsfB thus appears to serve a gatekeeper function in blocking the action of two
      sigma factors in the prespore: it prevents sigma(G) from becoming active before
      completion of engulfment and helps prevent sigma(E) from becoming active at all.

PMID- 20802043
TI  - Biogenesis of Salmonella enterica serovar typhimurium membrane vesicles provoked
      by induction of PagC.
AB  - Gram-negative bacteria ubiquitously release membrane vesicles (MVs) into the
      extracellular milieu. Although MVs are the product of growing bacteria, not of
      cell lysis or death, the regulatory mechanisms underlying MV formation remained
      unknown. We have found that MV biogenesis is provoked by the induction of PagC, a
      Salmonella-specific protein whose expression is activated by conditions that
      mimic acidified macrophage phagosomes. PagC is a major constituent of Salmonella
      MVs, and increased expression accelerates vesiculation. Expression of PagC is
      regulated at the posttranscriptional and/or posttranslational level in a sigmaS
      (RpoS)-dependent manner. Serial quantitative analysis has demonstrated that MV
      formation can accelerate when the quantity of the MV constituents, OmpX and PagC,
      rises. Overproduction of PagC dramatically impacts the difference in the relative
      amount of vesiculation, but the corresponding overproduction of OmpX was less
      pronounced. Quantitative examination of the ratios of PagC and OmpX in the
      periplasm, outer membrane, and MVs demonstrates that PagC is preferentially
      enriched in MVs released from Salmonella cells. This suggests that specific
      protein sorting mechanisms operate when MVs are formed. The possible role(s) of
      PagC-MV in host cells is discussed.

PMID- 20802045
TI  - Comparative genomic characterization of Actinobacillus pleuropneumoniae.
AB  - The Gram-negative bacterium Actinobacillus pleuropneumoniae is the etiologic
      agent of porcine contagious pleuropneumoniae, a lethal respiratory infectious
      disease causing great economic losses in the swine industry worldwide. In order
      to better interpret the genetic background of serotypic diversity, nine genomes
      of A. pleuropneumoniae reference strains of serovars 1, 2, 4, 6, 9, 10, 11, 12,
      and 13 were sequenced by using rapid high-throughput approach. Based on 12
      genomes of corresponding serovar reference strains including three publicly
      available complete genomes (serovars 3, 5b, and 7) of this bacterium, we
      performed a comprehensive analysis of comparative genomics and first reported a
      global genomic characterization for this pathogen. Clustering of 26,012 predicted
      protein-coding genes showed that the pan genome of A. pleuropneumoniae consists
      of 3,303 gene clusters, which contain 1,709 core genome genes, 822 distributed
      genes, and 772 strain-specific genes. The genome components involved in the
      biogenesis of capsular polysaccharide and lipopolysaccharide O antigen relative
      to serovar diversity were compared, and their genetic diversity was depicted. Our
      findings shed more light on genomic features associated with serovar diversity of
      A. pleuropneumoniae and provide broader insight into both pathogenesis research
      and clinical/epidemiological application against the severe disease caused by
      this swine pathogen.

PMID- 20802046
TI  - Complete genome sequence of Staphylococcus aureus strain JKD6008, an ST239 clone
      of methicillin-resistant Staphylococcus aureus with intermediate-level vancomycin
      resistance.
AB  - We report here the complete 2.92-Mb genome sequence of a clinical isolate of
      methicillin-resistant Staphylococcus aureus subsp. aureus that demonstrates
      intermediate-level vancomycin resistance. The strain, named JKD6008, belongs to
      multilocus sequence type 239 and was isolated from the bloodstream of a patient
      in New Zealand in 2003.

PMID- 20802047
TI  - Draft genome sequences of Actinobacillus pleuropneumoniae serotypes 2 and 6.
AB  - Actinobacillus pleuropneumoniae is a bacterial pathogen that causes highly
      contagious respiratory infection in pigs and has a serious impact on the
      production economy and animal welfare. As clear differences in virulence between
      serotypes have been observed, the genetic basis should be investigated at the
      genomic level. Here, we present the draft genome sequences of the A.
      pleuropneumoniae serotypes 2 (strain 4226) and 6 (strain Femo).

PMID- 20802048
TI  - Complete genome sequence of Methanothermobacter marburgensis, a methanoarchaeon
      model organism.
AB  - The circular genome sequence of the chemolithoautotrophic euryarchaeon
      Methanothermobacter marburgensis, with 1,639,135 bp, was determined and compared
      with that of Methanothermobacter thermautotrophicus. The genomes of the two model
      methanogens differ substantially in protein coding sequences, in insertion
      sequence (IS)-like elements, and in clustered regularly interspaced short
      palindromic repeats (CRISPR) loci.

PMID- 20802049
TI  - Fluctuating selection by water level on gynoecium colour polymorphism in an
      aquatic plant.
AB  - BACKGROUND AND AIMS: It has been proposed that variation in pollinator
      preferences or a fluctuating environment can act to maintain flower colour
      polymorphism. These two hypotheses were tested in an aquatic monocot Butomus
      umbellatus (Butomaceae) with a pink or white gynoecium in the field population.
      METHODS: Pollinator visitation was compared in experimental arrays of equivalent
      flowering cymes from both colour morphs. Seed set was compared between inter- and
      intramorph pollination under different water levels to test the effect of
      fluctuating environment on seed fertility. KEY RESULTS: Overall, the major
      pollinator groups did not discriminate between colour morphs. Compared with the
      white morph, seed production in the pink morph under intermorph, intramorph and
      open pollination treatments was significantly higher when the water level was low
      but not when it was high. Precipitation in July was correlated with yearly seed
      production in the pink morph but not in the white morph. CONCLUSIONS: The results
      indicated that the two colour morphs differed in their tolerance to water level.
      Our study on this aquatic plant provides additional evidence to support the
      hypothesis that flower colour polymorphism can be preserved by environmental
      heterogeneity.

PMID- 20802050
TI  - Synorganisation without organ fusion in the flowers of Geranium robertianum
      (Geraniaceae) and its not so trivial obdiplostemony.
AB  - BACKGROUND AND AIMS: Synorganisation of floral organs, an important means in
      angiosperm flower evolution, is mostly realized by congenital or post-genital
      organ fusion. Intimate synorganisation of many floral organs without fusion, as
      present in Geranium robertianum, is poorly known and needs to be studied.
      Obdiplostemony, the seemingly reversed position of two stamen whorls, widely
      distributed in core eudicots, has been the subject of much attention, but there
      is confusion in the literature. Obdiplostemony occurs in Geranium and whether and
      how it is involved in this synorganisation is explored here. METHODS: Floral
      development and architecture were studied with light microscopy based on
      microtome section series and with scanning electron microscopy. KEY RESULTS:
      Intimate synorganisation of floral organs is effected by the formation of five
      separate nectar canals for the proboscis of pollinators. Each nectar canal is
      formed by six adjacent organs from four organ whorls. In addition, the sepals are
      hooked together by the formation of longitudinal ribs and grooves, and provide a
      firm scaffold for the canals. Obdiplostemony provides a guide rail within each
      canal formed by the flanks of the antepetalous stamen filaments. CONCLUSIONS:
      Intimate synorganisation in flowers can be realized without any fusion, and
      obdiplostemony may play a role in this synorganisation.

PMID- 20802051
TI  - Epidemiology of ambulatory anesthesia for children in the United States: 2006 and
      1996.
AB  - BACKGROUND: There are few data that describe the frequency, anesthetic type,
      provider, or disposition of children requiring outpatient anesthesia in the
      United States (US). Since the early 1980s, the frequency of ambulatory surgery
      has increased dramatically because of advances in medical technology and changes
      in payment arrangements. Our primary aim in this study was to quantify the number
      of ambulatory anesthetics for children that occur annually and to study the
      change in utilization of pediatric anesthetic care over a decade. METHODS: The US
      National Center for Health Statistics performed the National Survey of Ambulatory
      Surgery in 1994 through 1996 and again in 2006. The survey is based on data
      abstracted from a national sample of ambulatory surgery centers and provides data
      on visits for surgical and nonsurgical procedures for patients of all ages. We
      abstracted data for children who had general anesthesia, regional anesthesia, or
      monitored anesthesia care during the ambulatory visit. We obtained the
      information from the 2006 and 1996 databases and used population census data to
      estimate the annual utilization of ambulatory anesthesia per 1000 children in the
      US. RESULTS: In 2006, an estimated 2.3 million ambulatory anesthesia episodes of
      care were provided in the US to children younger than 15 years (38 of 1000
      children). This amount compares with 26 per 1000 children of the same age group
      in 1996. In most cases, an anesthesiologist was involved in both time periods
      (74% in 2006 and 85% in 1996). Of the children, 14,200 were admitted to the
      hospital postoperatively, a rate of 6 per 1000 ambulatory anesthesia episodes.
      CONCLUSION: The number and rate of ambulatory anesthesia episodes for US children
      increased dramatically over a decade. This study provides an example of how
      databases can provide useful information to health care policy makers and
      educators on the utilization of ambulatory surgical centers by children.

PMID- 20802052
TI  - Oxygen delivery during transtracheal oxygenation: a comparison of two manual
      devices.
AB  - BACKGROUND: The ManujetTM and the ENK Oxygen Flow ModulatorTM (ENK) deliver
      oxygen during transtracheal oxygenation. We sought to describe the ventilation
      characteristics of these 2 devices. METHODS: The study was conducted in an
      artificial lung model consisting of a 15-cm ringed tube, simulating the trachea,
      connected via a flow analyzer and an artificial lung. A 15-gauge transtracheal
      wire reinforced catheter was used for transtracheal oxygenation. The ENK and
      Manujet were studied for 3 minutes at respiratory rates of 0, 4, and 12
      breaths/min, with and without the artificial lung, in a totally and a partially
      occluded airway. Statistical analysis was performed using analysis of variance
      followed by a Fisher exact test; P < 0.05 was considered significant. RESULTS:
      Gas flow and tidal volume were 3 times greater with the Manujet than the ENK
      (approximately 37 vs 14 L . min(-1) and 700 vs 250 mL, respectively) and were not
      dependent on the respiratory rate. In the absence of ventilation, the ENK
      delivered a 0.6 +/- 0.1 L . min(-1) constant gas flow. In the totally occluded
      airway, lung pressures increased to 136 cm H(2)O after 3 insufflations with the
      Manujet, whereas the ENK, which has a pressure release vent, generated acceptable
      pressures at a low respiratory rate (4 breaths/min) (peak pressure at 27.7 +/-
      0.7 and end-expiratory pressure at 18.8 +/- 3.8 cm H(2)O). When used at a
      respiratory rate of 12 breaths/min, the ENK generated higher pressures (peak
      pressure at 95.9 +/- 21.2 and end-expiratory pressure at 51.4 +/- 21.4 cm H(2)O).
      In the partially occluded airway, lung pressures were significantly greater with
      the Manujet compared with the ENK, and pressures increased with the respiratory
      rate with both devices. Finally, the gas flow and tidal volume generated by the
      Manujet varied proportionally with the driving pressure. DISCUSSION: This study
      confirms the absolute necessity of allowing gas exhalation between 2
      insufflations and maintaining low respiratory rates during transtracheal
      oxygenation. In the case of total airway obstruction, the ENK may be less
      deleterious because it has a pressure release vent. Using a Manujet at lower
      driving pressures may decrease the risk of barotrauma and allow the safe use of
      higher respiratory rates.

PMID- 20802054
TI  - Echo rounds: intraoperative transesophageal echocardiography-guided patent ductus
      arteriosus ligation in an asymptomatic nonbacterial endocarditis patient.

PMID- 20802053
TI  - Repinotan, a selective 5-HT1A-R-agonist, antagonizes morphine-induced ventilatory
      depression in anesthetized rats.
AB  - BACKGROUND: Spontaneous breathing during mechanical ventilation improves arterial
      oxygenation and cardiovascular function, but is depressed by opioids during
      critical care. Opioid-induced ventilatory depression was shown to be counteracted
      in anesthetized rats by serotonin(1A)-receptor (5-HT(1A)-R)-agonist 8-OH-DPAT,
      which cannot be applied to humans. Repinotan hydrochloride is a selective 5
      HT(1A)-R-agonist already investigated in humans, but the effects on ventilation
      and nociception are unknown. In this study, we sought to establish (a) the
      effects of repinotan on spontaneous breathing and nociception, and (b) the
      interaction with the standard opiate morphine. METHODS: The dose-dependent
      effects of repinotan, given alone or in combination with morphine, on spontaneous
      minute ventilation (MV) and nociceptive tail-flick reflex latencies (TFLs) were
      measured simultaneously in spontaneously breathing anesthetized rats. An
      additional series with NaCl 0.9% and the 5-HT(1A)-R-antagonist WAY 100 135 served
      as controls. RESULTS: (a) Repinotan dose-dependently activated spontaneous
      breathing (MV, mean [95% confidence interval]; 53% [29%-77%]) of pretreatment
      level) and suppressed nociception (TLF, 91% maximum possible effect [68%-114%])
      with higher doses of repinotan (2-200 MUg/kg). On the contrary, nociception was
      enhanced with a small dose of repinotan (0.2 MUg/kg; TFL, -47% maximum possible
      effect [-95% to 2%]). Effects were prevented by 5-HT(1A)-antagonist WAY 100 135.
      (B) Morphine-induced depression of ventilation (MV, -72% [-100% to -44%]) was
      reversed by repinotan (20 MUg/kg), which returned spontaneous ventilation to
      pretreatment levels (MV, 18% [-40% to 77%]). The morphine-induced complete
      depression of nociception was sustained throughout repinotan and NaCl 0.9%
      administration. Despite a mild decrease in mean arterial blood pressure, there
      were no serious cardiovascular side effects from repinotan. CONCLUSIONS: The 5
      HT(1A)-R-agonist repinotan activates spontaneous breathing in anesthetized rats
      even in morphine-induced ventilatory depression. The potency of 5-HT(1A)-R
      agonists to stimulate spontaneous breathing and their antinociceptive effects
      should be researched further.

PMID- 20802055
TI  - The anesthetic considerations of tracheobronchial foreign bodies in children: a
      literature review of 12,979 cases.
AB  - Asphyxiation by an inhaled foreign body is a leading cause of accidental death
      among children younger than 4 years. We analyzed the recent epidemiology of
      foreign body aspiration and reviewed the current trends in diagnosis and
      management. In this article, we discuss anesthetic management of bronchoscopy to
      remove objects. The reviewed articles total 12,979 pediatric bronchoscopies. Most
      aspirated foreign bodies are organic materials (81%, confidence interval [CI] =
      77%-86%), nuts and seeds being the most common. The majority of foreign bodies
      (88%, CI = 85%-91%) lodge in the bronchial tree, with the remainder catching in
      the larynx or trachea. The incidence of right-sided foreign bodies (52%, CI = 48%
      55%) is higher than that of left-sided foreign bodies (33%, CI = 30%-37%). A
      small number of objects fragment and lodge in different parts of the airways.
      Only 11% (CI = 8%-16%) of the foreign bodies were radio-opaque on radiograph,
      with chest radiographs being normal in 17% of children (CI = 13%-22%). Although
      rigid bronchoscopy is the traditional diagnostic "gold standard," the use of
      computerized tomography, virtual bronchoscopy, and flexible bronchoscopy is
      increasing. Reported mortality during bronchoscopy is 0.42%. Although asphyxia at
      presentation or initial emergency bronchoscopy causes some deaths, hypoxic
      cardiac arrest during retrieval of the object, bronchial rupture, and unspecified
      intraoperative complications in previously stable patients constitute the
      majority of in-hospital fatalities. Major complications include severe laryngeal
      edema or bronchospasm requiring tracheotomy or reintubation, pneumothorax,
      pneumomediastinum, cardiac arrest, tracheal or bronchial laceration, and hypoxic
      brain damage (0.96%). Aspiration of gastric contents is not reported.
      Preoperative assessment should determine where the aspirated foreign body has
      lodged, what was aspirated, and when the aspiration occurred ("what, where,
      when"). The choices of inhaled or IV induction, spontaneous or controlled
      ventilation, and inhaled or IV maintenance may be individualized to the
      circumstances. Although several anesthetic techniques are effective for managing
      children with foreign body aspiration, there is no consensus from the literature
      as to which technique is optimal. An induction that maintains spontaneous
      ventilation is commonly practiced to minimize the risk of converting a partial
      proximal obstruction to a complete obstruction. Controlled ventilation combined
      with IV drugs and paralysis allows for suitable rigid bronchoscopy conditions and
      a consistent level of anesthesia. Close communication between the
      anesthesiologist, bronchoscopist, and assistants is essential.

PMID- 20802056
TI  - Ipsilateral transversus abdominis plane block provides effective analgesia after
      appendectomy in children: a randomized controlled trial.
AB  - BACKGROUND: The transversus abdominis plane (TAP) block provides effective
      postoperative analgesia in adults undergoing major abdominal surgery. Its
      efficacy in children remains unclear, with no randomized clinical trials in this
      population. In this study, we evaluated its analgesic efficacy over the first 48
      postoperative hours after appendectomy performed through an open abdominal
      incision, in a randomized, controlled, double-blind clinical trial. METHODS:
      Forty children undergoing appendectomy were randomized to undergo unilateral TAP
      block with ropivacaine (n = 19) versus placebo (n = 21) in addition to standard
      postoperative analgesia comprising IV morphine analgesia and regular diclofenac
      and acetaminophen. All patients received a standard general anesthetic, and after
      induction of anesthesia, a TAP block was performed using the landmark technique
      with 2.5 mg . kg(-1) ropivacaine 0.75% or an equal volume (0.3 mL . kg(-1)) of
      saline on the ipsilateral side to the incision. RESULTS: The TAP block with
      ropivacaine reduced mean (+/- SD) morphine requirements in the first 48
      postoperative hours (10.3 +/- 12.7 vs 22.3 +/- 14.7 mg; P < 0.01) compared with
      placebo block. The TAP block also reduced postoperative visual analog scale pain
      scores at rest and on movement compared with placebo. Interval morphine
      consumption was reduced over the first 24 postoperative hours. There were no
      between-group differences in the incidence of sedation or nausea and vomiting.
      There were no complications attributable to the TAP block. CONCLUSIONS:
      Unilateral TAP block, as a component of a multimodal analgesic regimen, provided
      superior analgesia compared with placebo in the first 48 postoperative hours
      after appendectomy in children.

PMID- 20802057
TI  - Microbial evolution of sulphate reduction when lateral gene transfer is
      geographically restricted.
AB  - Lateral gene transfer (LGT) is an important mechanism by which micro-organisms
      acquire new functions. This process has been suggested to be central to
      prokaryotic evolution in various environments. However, the influence of
      geographical constraints on the evolution of laterally acquired genes in
      microbial metabolic evolution is not yet well understood. In this study, the
      influence of geographical isolation on the evolution of laterally acquired
      dissimilatory sulphite reductase (dsr) gene sequences in the sulphate-reducing
      micro-organisms (SRM) was investigated. Sequences on four continental blocks
      related to SRM known to have received dsr by LGT were analysed using standard
      phylogenetic and multidimensional statistical methods. Sequences related to
      lineages with large genetic diversity correlated positively with habitat
      divergence. Those affiliated to Thermodesulfobacterium indicated strong
      biogeographical delineation; hydrothermal-vent sequences clustered independently
      from hot-spring sequences. Some of the hydrothermal-vent and hot-spring sequences
      suggested to have been acquired from a common ancestral source may have diverged
      upon isolation within distinct habitats. In contrast, analysis of some
      Desulfotomaculum sequences indicated they could have been transferred from
      different ancestral sources but converged upon isolation within the same niche.
      These results hint that, after lateral acquisition of dsr genes, barriers to gene
      flow probably play a strong role in their subsequent evolution.

PMID- 20802058
TI  - Salinarimonas ramus sp. nov. and Tessaracoccus oleiagri sp. nov., isolated from a
      crude oil-contaminated saline soil.
AB  - Four bacterial strains, SL014B-41A4(T), SL014B-20A1(T), SL014B-76A1 and SL014B
      79A, isolated from a crude oil-contaminated saline soil of Shengli Oilfield,
      China, were investigated using a polyphasic approach. Phylogenetic analysis based
      on 16S rRNA gene sequences showed that strain SL014B-41A4(T) belonged to the
      genus Salinarimonas in the order Rhizobiales, with the highest sequence
      similarity with Salinarimonas rosea YIM YD3(T) (98.3 %). The DNA-DNA relatedness
      of strain SL014B-41A4(T) to S. rosea YIM YD3(T) was 27.03 +/- 3.0 %. Strain
      SL014B-41A4(T) was Gram-negative staining, facultatively anaerobic and produced
      deep red pigment in artificial seawater medium. Cells of strain SL014B-41A4(T)
      were rod-shaped (0.6-4.0 * 1.25-25 um), motile with a single polar flagellum and
      often formed branches. The strain contained Q-10 as the predominant respiratory
      ubiquinone and C(18 : 1)omega7c (57.5 %), C(16 : 0) (16.4 %) and 10-methyl C(19 :
      0) (9.1 %) as the major fatty acids. Strains SL014B-20A1(T), SL014B-76A1 and
      SL014B-79A were actinobacteria and belonged to the genus Tessaracoccus in the
      family Propionibacteriaceae of the order Actinomycetales with the highest 16S
      rRNA gene sequence similarities with Tessaracoccus flavescens SST-39(T) (96.4 %),
      Tessaracoccus lubricantis KISS-17Se(T) (96.2 %) and Tessaracoccus bendigoensis
      Ben 106(T) (94.7 %). Strains SL014B-20A1(T), SL014B-76A1 and SL014B-79A were Gram
      positive staining, facultatively anaerobic, non-endospore-forming, non-motile,
      acid-fast and oval to rod-shaped (0.48 * 0.5-1.0 um). These three novel strains
      had ll-diaminopimelic acid (DAP) as the diagnostic diamino acid in the cell-wall
      peptidoglycan, MK-9(H(4)) as the only menaquinone and anteiso-C(15 : 0) (67.11
      76.14 %) as the major cellular fatty acid. The G+C contents of the genomic DNA of
      strain SL014B-41A4(T) and strains SL014B-20A1(T), SL014B-76A1 and SL014B-79A were
      67.68 mol% and 65.65-67.17 mol%, respectively. Based on phenotypic and genotypic
      characteristics, strain SL014B-41A4(T) represents a novel species of the genus
      Salinarimonas, for which the name Salinarimonas ramus is proposed, with strain
      SL014B-41A4(T) ( = DSM 22962(T) = CGMCC 1.9161(T)) as the type strain. Strains
      SL014B-20A1(T), SL014B-76A1 and SL014B-79A represent a novel species of the genus
      Tessaracoccus, for which the name Tessaracoccus oleiagri is proposed, with strain
      SL014B-20A1(T) ( = DSM 22955(T) = CGMCC 1.9159(T)) as the type strain.

PMID- 20802059
TI  - Sphingobium wenxiniae sp. nov., a synthetic pyrethroid (SP)-degrading bacterium
      isolated from activated sludge in an SP-manufacturing wastewater treatment
      facility.
AB  - A synthetic pyrethroid (SP)-degrading bacterial strain, designated JZ-1(T), was
      isolated from activated sludge of a SP-manufacturing wastewater treatment
      facility and studied using a polyphasic taxonomic approach. Phylogenetic analysis
      based on 16S rRNA gene sequences indicated that strain JZ-1(T) belonged to the
      genus Sphingobium, showing highest sequence similarities to Sphingobium faniae
      DSM 21829(T) (98.6 %), Sphingobium cloacae JCM 10874(T) (98.5 %), Sphingobium
      vermicomposti DSM 21299(T) (97.4 %) and Sphingobium ummariense CCM 7431(T) (96.9
      %). The polar lipid pattern, the presence of spermidine and ubiquinone Q-10, the
      predominance of the cellular fatty acids C(18 : 1)omega7c, C(19 : 0) cyclo
      omega8c, 11 methyl C(18 : 1)omega7c, C(16 : 0) and C(14 : 0) 2-OH, and the G+C
      content of the genomic DNA also supported the affiliation of the strain with the
      genus Sphingobium. Strain JZ-1(T) showed low DNA-DNA relatedness values with S.
      faniae DSM 21829(T) (30.2 %), S. cloacae JCM 10874(T) (23.3 %), S. vermicomposti
      DSM 21299(T) (10.9 %) and S. ummariense CCM 7431(T) (7.9 %). Based on its
      phylogenetic position and its phenotypic and genotypic properties, strain JZ-1(T)
      represents a novel species of the genus Sphingobium, for which the name
      Sphingobium wenxiniae sp. nov. is proposed. The type strain is JZ-1(T) ( = CGMCC
      1.7748(T)  = DSM 21828(T)).

PMID- 20802060
TI  - Rhizomicrobium electricum sp. nov., a facultatively anaerobic, fermentative,
      prosthecate bacterium isolated from a cellulose-fed microbial fuel cell.
AB  - A facultatively anaerobic, prosthecate bacterium, strain Mfc52(T), was isolated
      from a microbial fuel cell inoculated with soil and fed with cellulose as the
      sole fuel. Cells were Gram-negative, non-spore-forming, straight or slightly
      curved rods, and some of them had one or two polar prosthecae (stalks). Cells
      reproduced by binary fission or by budding from mother cells having prosthecae.
      Strain Mfc52(T) fermented various sugars and produced lactate, acetate and
      fumarate. Ferric iron, nitrate, oxygen and fumarate served as electron acceptors,
      while sulfate and malate did not. Nitrate was reduced to nitrite. The DNA G+C
      content was 64.7 mol%. On the basis of 16S rRNA gene sequence phylogeny, strain
      Mfc52(T) was affiliated with the genus Rhizomicrobium in the class
      Alphaproteobacteria and most closely related to Rhizomicrobium palustre with a
      sequence similarity of 97 %. Based on these physiological and phylogenetic
      characteristics, the name Rhizomicrobium electricum sp. nov. is proposed; the
      type strain is Mfc52(T) ( = JCM 15089(T)  = KCTC 5806(T)).

PMID- 20802061
TI  - Modestobacter marinus sp. nov., a psychrotolerant actinobacterium from deep-sea
      sediment, and emended description of the genus Modestobacter.
AB  - The taxonomic status of an actinobacterium that changed colour during growth,
      strain 42H12-1(T), isolated from deep-sea sediment collected from the Atlantic
      Ocean, was established using a combination of genotypic and phenotypic data.
      Strain 42H12-1(T) formed a distinct branch in the 16S rRNA gene phylogenetic tree
      together with the type strains in the genus Modestobacter. The highest sequence
      similarity by blast analysis was to Modestobacter versicolor CP153-2(T) (98.5 %)
      and the second-highest sequence similarity was to Modestobacter multiseptatus AA
      826(T) (97.5 %). DNA-DNA relatedness of only 12 % (sd 1.82 %) between strain
      42H12-1(T) and M. versicolor DSM 16678(T) differentiated them as members of
      separate genomic species. Colonies of strain 42H12-1(T) were black on
      oligotrophic medium, but orange to red, turning black, on copiotrophic medium.
      The peptidoglycan contained meso-diaminopimelic acid. The polar lipids were
      diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol,
      phosphatidylinositol and an unknown aminophospholipid. The predominant
      menaquinone was MK-9(H(4)). The major fatty acids were iso-C(16 : 0) and C(17 :
      1)omega8c. The DNA G+C content was 72.3+/-1 mol%. Strain 42H12-1(T) ( = DSM
      45201(T)  = CGMCC 4.5581(T)) is assigned as the type strain of a novel species of
      the genus Modestobacter, for which the name Modestobacter marinus sp. nov. is
      proposed.

PMID- 20802062
TI  - Tumebacillus ginsengisoli sp. nov., isolated from soil of a ginseng field.
AB  - A gram-reaction-positive, rod-shaped, spore-forming bacterium, designated Gsoil
      1105(T), was isolated from soil of a ginseng field in Pocheon Province in South
      Korea and characterized in order to determine its taxonomic position. Comparative
      analysis of the 16S rRNA gene sequence showed that the isolate belongs to the
      order Bacillales, showing the highest level of sequence similarity with respect
      to Tumebacillus permanentifrigoris Eur1 9.5(T) (94.6 %). The phylogenetic
      distances from other described species with validly published names within the
      order Bacillales were greater than 9.0 %. Strain Gsoil 1105(T) had a genomic DNA
      G+C content of 55.6 mol% and menaquinone 7 (MK-7) as the major respiratory
      quinone. The major fatty acids were iso-C(15 : 0) and anteiso-C(15 : 0). On the
      basis of its phenotypic properties and phylogenetic distinctiveness, strain Gsoil
      1105(T) represents a novel species of the genus Tumebacillus, for which the name
      Tumebacillus ginsengisoli sp. nov. is proposed. The type strain is Gsoil 1105(T)
      ( = KCTC 13942(T)  = DSM 18389(T)).

PMID- 20802063
TI  - Jeotgalicoccus halophilus sp. nov., isolated from salt lakes.
AB  - Two slightly halophilic bacterial strains, C1-52(T) and YD-9, were isolated from
      Daban and Aiding salt lakes in Xinjiang, China, respectively. The isolates were
      gram-positive, non-endospore-forming, non-motile, facultatively anaerobic cocci.
      Colonies were pale yellow, and a light pink, diffusible pigment was produced
      after a few additional days of incubation. The isolates grew optimally with 2-3 %
      (w/v) NaCl, at pH 7.5 and at 30-35  degrees C. The peptidoglycan type was L-Lys
      Gly(3-4)-L-Ala(Gly). The menaquinones were MK-7 (83.2 %) and MK-6 (16.8 %). The
      major fatty acids (>10 %) were anteiso-C(15 : 0) and iso-C(15 : 0). The DNA G+C
      content of strains C1-52(T) and YD-9 was 41.2 and 41.0 mol%, respectively.
      Phylogenetic analysis based on 16S rRNA gene sequences revealed that strains C1
      52(T) and YD-9 were closely related to Jeotgalicoccus psychrophilus YKJ-115(T)
      (98.0 and 97.1 % 16S rRNA gene sequence similarity, respectively), followed by
      Jeotgalicoccus halotolerans YKJ-101(T) (97.1 and 96.8 %). Strains C1-52(T) and YD
      9 shared, respectively, 20 and 11 % DNA-DNA relatedness with J. halotolerans JCM
      11198(T) and 8 and 13 % with J. psychrophilus JCM 11199(T). DNA-DNA relatedness
      between the isolates was 91 %. On the basis of phenotypic and phylogenetic
      distinctiveness, strains C1-52(T) and YD-9 belonged to the same species, which
      should be placed in the genus Jeotgalicoccus as a novel species. The name
      Jeotgalicoccus halophilus sp. nov. is proposed, with the type strain C1-52(T) ( =
      CGMCC 1.8911(T)  = NBRC 105788(T)).

PMID- 20802064
TI  - Agromyces flavus sp. nov., an actinomycete isolated from soil.
AB  - A gram-positive, non-motile strain, designated CPCC 202695(T), was isolated from
      a soil sample collected from the Qinghai-Tibet plateau, north-west China. Strain
      CPCC 202695(T) contained rhamnose, glucose and galactose in the cell wall as
      diagnostic sugars and 2,4-diaminobutyric acid, alanine, glutamic acid and glycine
      in the peptidoglycan. The polar lipids consisted of diphosphatidylglycerol,
      phosphatidylglycerol and two unknown glycolipids. MK-12 was the predominant
      menaquinone and anteiso-C(15 : 0) (34.2 %), iso-C(15 : 0) (19.8 %), iso-C(16 : 0)
      (12.7 %) and anteiso-C(17 : 0) (11.1 %) were the major fatty acids. 16S rRNA gene
      sequence similarities (94.2-97.1 %) between the isolate and the type strains of
      recognized species of the genus Agromyces indicated that strain CPCC 202695(T)
      was a member of the genus Agromyces. DNA-DNA relatedness clearly separated strain
      CPCC 202695(T) from its closest relatives. The phenotypic and genotypic data
      demonstrated that strain CPCC 202695(T) represents a novel species of the genus
      Agromyces, for which the name Agromyces flavus sp. nov. is proposed. The type
      strain is CPCC 202695(T) ( = KCTC 19578(T)  = CCM 7623(T)).

PMID- 20802065
TI  - Vertical distribution of ammonia-oxidizing crenarchaeota and methanogens in the
      epipelagic waters of Lake Kivu (Rwanda-Democratic Republic of the Congo).
AB  - Four stratified basins in Lake Kivu (Rwanda-Democratic Republic of the Congo)
      were sampled in March 2007 to investigate the abundance, distribution, and
      potential biogeochemical role of planktonic archaea. We used fluorescence in situ
      hybridization with catalyzed-reported deposition microscopic counts (CARD-FISH),
      denaturing gradient gel electrophoresis (DGGE) fingerprinting, and quantitative
      PCR (qPCR) of signature genes for ammonia-oxidizing archaea (16S rRNA for marine
      Crenarchaeota group 1.1a [MCG1] and ammonia monooxygenase subunit A [amoA]).
      Abundance of archaea ranged from 1 to 4.5% of total DAPI (4',6-diamidino-2
      phenylindole) counts with maximal concentrations at the oxic-anoxic transition
      zone (~50-m depth). Phylogenetic analysis of the archaeal planktonic community
      revealed a higher level of richness of crenarchaeal 16S rRNA gene sequences (21
      of the 28 operational taxonomic units [OTUs] identified [75%]) over
      euryarchaeotal ones (7 OTUs). Sequences affiliated with the kingdom Euryarchaeota
      were mainly recovered from the anoxic water compartment and mostly grouped into
      methanogenic lineages (Methanosarcinales and Methanocellales). In turn,
      crenarchaeal phylotypes were recovered throughout the sampled epipelagic waters
      (0- to 100-m depth), with clear phylogenetic segregation along the transition
      from oxic to anoxic water masses. Thus, whereas in the anoxic hypolimnion
      crenarchaeotal OTUs were mainly assigned to the miscellaneous crenarchaeotic
      group, the OTUs from the oxic-anoxic transition and above belonged to
      Crenarchaeota groups 1.1a and 1.1b, two lineages containing most of the ammonia
      oxidizing representatives known so far. The concomitant vertical distribution of
      both nitrite and nitrate maxima and the copy numbers of both MCG1 16S rRNA and
      amoA genes suggest the potential implication of Crenarchaeota in nitrification
      processes occurring in the epilimnetic waters of the lake.

PMID- 20802067
TI  - Enhancement of targeted homologous recombination in Mycoplasma mycoides subsp.
      capri by inclusion of heterologous recA.
AB  - A suicide plasmid, pExp1-ctpA::tetM-recAec, employing recA from Escherichia coli
      and tetM as a selection marker, was used to generate ctpA knockout mutants in
      Mycoplasma mycoides subsp. capri through targeted gene disruption. Inclusion of
      E. coli recA greatly enhanced both the consistency and the recovery of mutants
      generated by homologous recombination.

PMID- 20802066
TI  - Broad conservation of milk utilization genes in Bifidobacterium longum subsp.
      infantis as revealed by comparative genomic hybridization.
AB  - Human milk oligosaccharides (HMOs) are the third-largest solid component of milk.
      Their structural complexity renders them nondigestible to the host but liable to
      hydrolytic enzymes of the infant colonic microbiota. Bifidobacteria and,
      frequently, Bifidobacterium longum strains predominate the colonic microbiota of
      exclusively breast-fed infants. Among the three recognized subspecies of B.
      longum, B. longum subsp. infantis achieves high levels of cell growth on HMOs and
      is associated with early colonization of the infant gut. The B. longum subsp.
      infantis ATCC 15697 genome features five distinct gene clusters with the
      predicted capacity to bind, cleave, and import milk oligosaccharides. Comparative
      genomic hybridizations (CGHs) were used to associate genotypic biomarkers among
      15 B. longum strains exhibiting various HMO utilization phenotypes and host
      associations. Multilocus sequence typing provided taxonomic subspecies
      designations and grouped the strains between B. longum subsp. infantis and B.
      longum subsp. longum. CGH analysis determined that HMO utilization gene regions
      are exclusively conserved across all B. longum subsp. infantis strains capable of
      growth on HMOs and have diverged in B. longum subsp. longum strains that cannot
      grow on HMOs. These regions contain fucosidases, sialidases, glycosyl hydrolases,
      ABC transporters, and family 1 solute binding proteins and are likely needed for
      efficient metabolism of HMOs. Urea metabolism genes and their activity were
      exclusively conserved in B. longum subsp. infantis. These results imply that the
      B. longum has at least two distinct subspecies: B. longum subsp. infantis,
      specialized to utilize milk carbon, and B. longum subsp. longum, specialized for
      plant-derived carbon metabolism.

PMID- 20802068
TI  - Acquisition of iron by alkaliphilic bacillus species.
AB  - The biochemical and molecular mechanisms used by alkaliphilic bacteria to acquire
      iron are unknown. We demonstrate that alkaliphilic (pH > 9) Bacillus species are
      sensitive to artificial iron (Fe3+) chelators and produce iron-chelating
      molecules. These alkaliphilic siderophores contain catechol and hydroxamate
      moieties, and their synthesis is stimulated by manganese(II) salts and suppressed
      by FeCl3 addition. Purification and mass spectrometric characterization of the
      siderophore produced by Caldalkalibacillus thermarum failed to identify any
      matches to previously observed fragmentation spectra of known siderophores,
      suggesting a novel structure.

PMID- 20802069
TI  - Quantitative fluorescence in situ hybridization of microbial communities in the
      rumens of cattle fed different diets.
AB  - At present there is little quantitative information on the identity and
      composition of bacterial populations in the rumen microbial community.
      Quantitative fluorescence in situ hybridization using newly designed
      oligonucleotide probes was applied to identify the microbial populations in
      liquid and solid fractions of rumen digesta from cows fed barley silage or grass
      hay diets with or without flaxseed. Bacteroidetes, Firmicutes, and Proteobacteria
      were abundant in both fractions, constituting 31.8 to 87.3% of the total cell
      numbers. They belong mainly to the order Bacteroidales (0.1 to 19.2%),
      hybridizing with probe BAC1080; the families Lachnospiraceae (9.3 to 25.5%) and
      Ruminococcaceae (5.5 to 23.8%), hybridizing with LAC435 and RUM831, respectively;
      and the classes Deltaproteobacteria (5.8 to 28.3%) and Gammaproteobacteria (1.2
      to 8.2%). All were more abundant in the rumen communities of cows fed diets
      containing silage (75.2 to 87.3%) than in those of cows fed diets containing hay
      (31.8 to 49.5%). The addition of flaxseed reduced their abundance in the rumens
      of cows fed silage-based diets (to 45.2 to 58.7%) but did not change markedly
      their abundance in the rumens of cows fed hay-based diets (31.8 to 49.5%).
      Fibrolytic species, including Fibrobacter succinogenes and Ruminococcus spp., and
      archaeal methanogens accounted for only a small proportion (0.4 to 2.1% and 0.2
      to 0.6%, respectively) of total cell numbers. Depending on diet, between 37.0 and
      91.6% of microbial cells specifically hybridized with the probes used in this
      study, allowing them to be identified in situ. The identities of other microbial
      populations (8.4 to 63.0%) remain unknown.

PMID- 20802070
TI  - Quantification of nitrogen reductase and nitrite reductase genes in soil of
      thinned and clear-cut Douglas-fir stands by using real-time PCR.
AB  - The abundance of nifH, nirS, and nirK gene fragments involved in nitrogen (N)
      fixation and denitrification in thinned second-growth Douglas-fir (Pseudotsuga
      menziesii subsp. menziesii [Mirb.] Franco) forest soil was investigated by using
      quantitative real-time PCR. Prokaryotic N cycling is an important aspect of N
      availability in forest soil. The abundance of universal nifH, Azotobacter sp.
      specific nifH (nifH-g1), nirS, and nirK gene fragments in unthinned control and
      30, 90, and 100% thinning treatments were compared at two long-term research
      sites on Vancouver Island, Canada. The soil was analyzed for organic matter (OM),
      total carbon (C), total N, NH4-N, NO3-N, and phosphorus (P). The soil horizon
      accounted for the greatest variation in nutrient status, followed by the site
      location. The 30% thinning treatment was associated with significantly greater
      nifH-g1 abundance than the control treatment in one site; at the same site, nirS
      in the mineral soil horizon was significantly reduced by thinning. The abundance
      of nirS genes significantly correlated with the abundance of nirK genes. In
      addition, significant correlations were observed between nifH-g1 abundance and C
      and N in the organic horizon and between nirS and nirK and N in the mineral
      horizon. Overall, no clear influence of tree thinning on nifH, nirS, and nirK was
      observed. However, soil OM, C, and N were found to significantly influence N
      cycling gene abundance.

PMID- 20802071
TI  - Proteolytic enzyme production by strains of the insect pathogen xenorhabdus and
      characterization of an early-log-phase-secreted protease as a potential virulence
      factor.
AB  - As a comparison to a similar study on Photorhabdus strains, 15 Xenorhabdus
      bacterial strains and secondary phenotypic variants of two strains were screened
      for proteolytic activity by five detection methods. Although the number and
      intensity of proteolytic activities were different, every strain was positive for
      proteolytic activity by several tests. Zymography following native PAGE detected
      two groups of activities with different substrate affinities and a higher and
      lower electrophoretic mobility that were distinguished as activity 1 and 2,
      respectively. Zymography following SDS-PAGE resolved three activities, which were
      provisionally named proteases A, B, and C. Only protease B, an ~55-kDa enzyme,
      was produced by every strain. This enzyme exhibited higher affinity to the
      gelatin substrate than to the casein substrate. Of the chromogenic substrates
      used, three were hydrolyzed: furylacryloyl-Ala-Leu-Val-Tyr (Fua-ALVY), Fua-LGPA
      (LGPA is Leu-Gly-Pro-Ala) (a substrate for collagen peptidases), and succinyl-Ala
      Ala-Pro-Phe-thiobenzyl (Succ-AAPF-SBzl). All but the Fua-LGPA-ase activity seemed
      to be from secreted enzymes. According to their substrate preference profiles and
      inhibitor sensitivities, at least six such proteolytic enzymes could be
      distinguished in the culture medium of Xenorhabdus strains. The proteolytic
      enzyme that was secreted the earliest, protease B and the Succ-AAPF-SBzl
      hydrolyzing enzyme, appeared from the early logarithmic phase of growth. Protease
      B could also be detected in the hemolymph of Xenorhabdus-infected Galleria
      mellonella larvae from 15 h postinfection. The purified protease B hydrolyzed in
      vitro seven proteins in the hemolymph of Manduca sexta that were also cleaved by
      PrtA peptidase from Photorhabdus. The N-terminal sequence of protease B showed
      similarity to a 55-kDa serralysin type metalloprotease in Xenorhabdus
      nematophila, which had been identified as an orthologue of Photorhabdus PrtA
      peptidase.

PMID- 20802072
TI  - Effect of estuarine wetland degradation on transport of Toxoplasma gondii
      surrogates from land to sea.
AB  - The flux of terrestrially derived pathogens to coastal waters presents a
      significant health risk to marine wildlife, as well as to humans who utilize the
      nearshore for recreation and seafood harvest. Anthropogenic changes in natural
      habitats may result in increased transmission of zoonotic pathogens to coastal
      waters. The objective of our work was to evaluate how human-caused alterations of
      coastal landscapes in California affect the transport of Toxoplasma gondii to
      estuarine waters. Toxoplasma gondii is a protozoan parasite that is excreted in
      the feces of infected felids and is thought to reach coastal waters in
      contaminated runoff. This zoonotic pathogen causes waterborne toxoplasmosis in
      humans and is a significant cause of death in threatened California sea otters.
      Surrogate particles that mimic the behavior of T. gondii oocysts in water were
      released in transport studies to evaluate if the loss of estuarine wetlands is
      contributing to an increased flux of oocysts into coastal waters. Compared to
      vegetated sites, more surrogates were recovered from unvegetated mudflat
      habitats, which represent degraded wetlands. Specifically, in Elkhorn Slough,
      where a large proportion of otters are infected with T. gondii, erosion of 36% of
      vegetated wetlands to mudflats may increase the flux of oocysts by more than 2
      orders of magnitude. Total degradation of wetlands may result in increased
      Toxoplasma transport of 6 orders of magnitude or more. Destruction of wetland
      habitats along central coastal California may thus facilitate pathogen pollution
      in coastal waters with detrimental health impacts to wildlife and humans.

PMID- 20802073
TI  - Sensitization of microcin J25-resistant strains by a membrane-permeabilizing
      peptide.
AB  - Microcin J25 (MccJ25) is a plasmid-encoded, 21-amino-acid, antibacterial peptide
      produced by Escherichia coli. MccJ25 inhibits RNA polymerase and the membrane
      respiratory chain. MccJ25 uptake into E. coli-sensitive strains is mediated by
      the outer membrane receptor FhuA and the inner membrane proteins TonB, ExbB,
      ExbD, and SbmA. This peptide is active on some E. coli, Salmonella, and Shigella
      species strains, while other Gram-negative bacteria, such as clinical isolates of
      Enterobacter cloacae, Citrobacter freundii, Klebsiella pneumoniae, Pseudomonas
      aeruginosa, Acinetobacter baumannii, Moraxella catarrhalis, and Salmonella
      enterica serovar Typhimurium, are completely resistant. In the present work, we
      demonstrated that the membrane-permeabilizing peptide (KFF)3K made some resistant
      strains sensitive to MccJ25, among them S. Typhimurium, where the antibiotic
      inhibits in vitro cell growth and bacterial replication within macrophages. The
      results demonstrate that the membrane permeabilization induced by (KFF)3K allows
      MccJ25 penetration in an FhuA and SbmA-independent manner and suggest that the
      combination of both peptides could be considered as a therapeutic agent against
      pathogenic Salmonella strains.

PMID- 20802074
TI  - Comparative analysis of myxococcus predation on soil bacteria.
AB  - Predator-prey relationships among prokaryotes have received little attention but
      are likely to be important determinants of the composition, structure, and
      dynamics of microbial communities. Many species of the soil-dwelling myxobacteria
      are predators of other microbes, but their predation range is poorly
      characterized. To better understand the predatory capabilities of myxobacteria in
      nature, we analyzed the predation performance of numerous Myxococcus isolates
      across 12 diverse species of bacteria. All predator isolates could utilize most
      potential prey species to effectively fuel colony expansion, although one species
      hindered predator swarming relative to a control treatment with no growth
      substrate. Predator strains varied significantly in their relative performance
      across prey types, but most variation in predatory performance was determined by
      prey type, with Gram-negative prey species supporting more Myxococcus growth than
      Gram-positive species. There was evidence for specialized predator performance in
      some predator-prey combinations. Such specialization may reduce resource
      competition among sympatric strains in natural habitats. The broad prey range of
      the Myxococcus genus coupled with its ubiquity in the soil suggests that
      myxobacteria are likely to have very important ecological and evolutionary
      effects on many species of soil prokaryotes.

PMID- 20802075
TI  - Use of purified Clostridium difficile spores to facilitate evaluation of health
      care disinfection regimens.
AB  - Clostridium difficile is a major cause of antibiotic-associated diarrheal disease
      in many parts of the world. In recent years, distinct genetic variants of C.
      difficile that cause severe disease and persist within health care settings have
      emerged. Highly resistant and infectious C. difficile spores are proposed to be
      the main vectors of environmental persistence and host transmission, so methods
      to accurately monitor spores and their inactivation are urgently needed. Here we
      describe simple quantitative methods, based on purified C. difficile spores and a
      murine transmission model, for evaluating health care disinfection regimens. We
      demonstrate that disinfectants that contain strong oxidizing active ingredients,
      such as hydrogen peroxide, are very effective in inactivating pure spores and
      blocking spore-mediated transmission. Complete inactivation of 106 pure C.
      difficile spores on indicator strips, a six-log reduction, and a standard measure
      of stringent disinfection regimens require at least 5 min of exposure to hydrogen
      peroxide vapor (HPV; 400 ppm). In contrast, a 1-min treatment with HPV was
      required to disinfect an environment that was heavily contaminated with C.
      difficile spores (17 to 29 spores/cm2) and block host transmission. Thus, pure C.
      difficile spores facilitate practical methods for evaluating the efficacy of C.
      difficile spore disinfection regimens and bringing scientific acumen to C.
      difficile infection control.

PMID- 20802076
TI  - Isolation and characterization of 4-tert-butylphenol-utilizing Sphingobium
      fuliginis strains from Phragmites australis rhizosphere sediment.
AB  - We isolated three Sphingobium fuliginis strains from Phragmites australis
      rhizosphere sediment that were capable of utilizing 4-tert-butylphenol as a sole
      carbon and energy source. These strains are the first 4-tert-butylphenol
      utilizing bacteria. The strain designated TIK-1 completely degraded 1.0 mM 4-tert
      butylphenol in basal salts medium within 12 h, with concomitant cell growth. We
      identified 4-tert-butylcatechol and 3,3-dimethyl-2-butanone as internal
      metabolites by gas chromatography-mass spectrometry. When 3-fluorocatechol was
      used as an inactivator of meta-cleavage enzymes, strain TIK-1 could not degrade 4
      tert-butylcatechol and 3,3-dimethyl-2-butanone was not detected. We concluded
      that metabolism of 4-tert-butylphenol by strain TIK-1 is initiated by
      hydroxylation to 4-tert-butylcatechol, followed by a meta-cleavage pathway.
      Growth experiments with 20 other alkylphenols showed that 4-isopropylphenol, 4
      sec-butylphenol, and 4-tert-pentylphenol, which have alkyl side chains of three
      to five carbon atoms with alpha-quaternary or alpha-tertiary carbons, supported
      cell growth but that 4-n-alkylphenols, 4-tert-octylphenol, technical nonylphenol,
      2-alkylphenols, and 3-alkylphenols did not. The rate of growth on 4-tert
      butylphenol was much higher than that of growth on the other alkylphenols.
      Degradation experiments with various alkylphenols showed that strain TIK-1 cells
      grown on 4-tert-butylphenol could degrade 4-alkylphenols with variously sized and
      branched side chains (ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl,
      n-pentyl, tert-pentyl, n-hexyl, n-heptyl, n-octyl, tert-octyl, n-nonyl, and
      branched nonyl) via a meta-cleavage pathway but not 2- or 3-alkylphenols. Along
      with the degradation of these alkylphenols, we detected methyl alkyl ketones that
      retained the structure of the original alkyl side chains. Strain TIK-1 may be
      useful in the bioremediation of environments polluted by 4-tert-butylphenol and
      various other 4-alkylphenols.

PMID- 20802077
TI  - Extracts of edible and medicinal plants damage membranes of Vibrio cholerae.
AB  - The use of natural compounds from plants can provide an alternative approach
      against food-borne pathogens. The mechanisms of action of most plant extracts
      with antimicrobial activity have been poorly studied. In this work, changes in
      membrane integrity, membrane potential, internal pH (pH(in)), and ATP synthesis
      were measured in Vibrio cholerae cells after exposure to extracts of edible and
      medicinal plants. A preliminary screen of methanolic, ethanolic, and aqueous
      extracts of medicinal and edible plants was performed. Minimal bactericidal
      concentrations (MBCs) were measured for extracts showing high antimicrobial
      activity. Our results indicate that methanolic extracts of basil (Ocimum
      basilicum L.), nopal cactus (Opuntia ficus-indica var. Villanueva L.), sweet
      acacia (Acacia farnesiana L.), and white sagebrush (Artemisia ludoviciana Nutt.)
      are the most active against V. cholera, with MBCs ranging from 0.5 to 3.0 mg/ml.
      Using four fluorogenic techniques, we studied the membrane integrity of V.
      cholerae cells after exposure to these four extracts. Extracts from these plants
      were able to disrupt the cell membranes of V. cholerae cells, causing increased
      membrane permeability, a clear decrease in cytoplasmic pH, cell membrane
      hyperpolarization, and a decrease in cellular ATP concentration in all strains
      tested. These four plant extracts could be studied as future alternatives to
      control V. cholerae contamination in foods and the diseases associated with this
      microorganism.

PMID- 20802078
TI  - Differential phenotypic diversity among epidemic-spanning Salmonella enterica
      serovar enteritidis isolates from humans or animals.
AB  - Nontyphoidal salmonellae are major causes of food-borne disease worldwide. In
      Uruguay, Salmonella enterica serovar Enteritidis was the most commonly isolated
      serovar throughout the last decade, with a marked epidemic period between 1995
      and 2004. In a previous study, we conducted comparative genomics of 29 epidemic
      spanning S. Enteritidis field isolates, and here we evaluated the pathogenic
      potential of the same set of isolates using several phenotypic assays. The sample
      included 15 isolates from human gastroenteritis, 5 from invasive disease, and 9
      from nonhuman sources. Contrary to the genetic homogeneity previously observed,
      we found great phenotypic variability among these isolates. One-third of them
      were defective in at least one assay, namely, 10 isolates were defective in
      motility, 8 in invasion of Caco-2 cells, and 10 in survival in egg albumen.
      Twelve isolates were tested for invasiveness in 3-day-old chickens, and five of
      these were significantly less invasive than the reference strain. The two oldest
      preepidemic isolates were reduced in fitness in all assays, providing a plausible
      explanation for the previous negligible incidence of S. Enteritidis in Uruguay
      and supporting the view that the introduction or emergence of a more virulent
      strain was responsible for the marked rise of this serovar. Further, we found
      differences in fitness among the isolates which depended on the source of
      isolation. A total of 1 out of 14 isolates from human gastroenteritis, but 6 out
      of 13 isolates from other sources, was impaired in at least two assays,
      suggesting enhanced fitness among strains able to cause intestinal disease in
      humans.

PMID- 20802079
TI  - Link between phosphate starvation and glycogen metabolism in Corynebacterium
      glutamicum, revealed by metabolomics.
AB  - In this study, we analyzed the influence of phosphate (P(i)) limitation on the
      metabolism of Corynebacterium glutamicum. Metabolite analysis by gas
      chromatography-time-of-flight (GC-TOF) mass spectrometry of cells cultivated in
      glucose minimal medium revealed a greatly increased maltose level under P(i)
      limitation. As maltose formation could be linked to glycogen metabolism, the
      cellular glycogen content was determined. Unlike in cells grown under P(i)
      excess, the glycogen level in P(i)-limited cells remained high in the stationary
      phase. Surprisingly, even acetate-grown cells, which do not form glycogen under
      P(i) excess, did so under P(i) limitation and also retained it in stationary
      phase. Expression of pgm and glgC, encoding the first two enzymes of glycogen
      synthesis, phosphoglucomutase and ADP-glucose pyrophosphorylase, was found to be
      increased 6- and 3-fold under P(i) limitation, respectively. Increased glycogen
      synthesis together with a decreased glycogen degradation might be responsible for
      the altered glycogen metabolism. Independent from these experimental results,
      flux balance analysis suggested that an increased carbon flux to glycogen is a
      solution for C. glutamicum to adapt carbon metabolism to limited P(i)
      concentrations.

PMID- 20802080
TI  - Diversity and abundance of zoonotic pathogens and indicators in manures of
      feedlot cattle in Australia.
AB  - The occurrence of 10 pathogens and three fecal indicators was assessed by
      quantitative PCR in manures of Australian feedlot cattle. Most samples tested
      positive for one or more pathogens. For the dominant pathogens Campylobacter
      jejuni, Listeria monocytogenes, Giardia spp., Cryptosporidium spp., and eaeA
      positive Escherichia coli, 102 to 107 genome copies g-1 (dry weight) manure were
      recovered.

PMID- 20802081
TI  - Bartonella genotypes in fleas (insecta: siphonaptera) collected from rodents in
      the negev desert, Israel.
AB  - Fleas collected from rodents in the Negev Desert in southern Israel were
      molecularly screened for Bartonella species. A total of 1,148 fleas, collected
      from 122 rodents belonging to six species, were pooled in 245 pools based on flea
      species, sex, and rodent host species. Two Bartonella gene fragments,
      corresponding to RNA polymerase B (rpoB) and citrate synthase (gltA), were
      targeted, and 94 and 74 flea pools were found positive by PCR, respectively. The
      Bartonella 16S-23S internal transcribed spacer (ITS) region was also targeted,
      and 66 flea pools were found to be positive by PCR. Sixteen different Bartonella
      gltA genotypes were detected in 94 positive flea pools collected from 5 different
      rodent species, indicating that fleas collected from each rodent species can
      harbor several Bartonella genotypes. Based on gltA analysis, identified
      Bartonella genotypes were highly similar or identical to strains previously
      detected in rodent species from different parts of the world. A gltA fragment
      100% similar to Bartonella henselae was detected in one flea pool. Another 2 flea
      pools contained gltA fragments that were closely related to B. henselae (98%
      similarity). The high sequence similarities to the zoonotic pathogen B. henselae
      warrant further investigation.

PMID- 20802082
TI  - Development of a genetic system for combinatorial biosynthesis of lipopeptides in
      Streptomyces fradiae and heterologous expression of the A54145 biosynthesis gene
      cluster.
AB  - A54145 factors are calcium-dependent lipopeptide antibiotics produced by
      Streptomyces fradiae NRRL 18160. A54145 is structurally related to the clinically
      important daptomycin, and as such may be a useful scaffold for the development of
      a novel lipopeptide antibiotic. We developed methods to genetically manipulate S.
      fradiae by deletion mutagenesis and conjugal transfer of plasmids from
      Escherichia coli. Cloning the complete pathway on a bacterial artificial
      chromosome (BAC) vector and the construction of ectopic trans-complementation
      with plasmids utilizing the phiC31 or phiBT1 site-specific integration system
      allowed manipulation of A54145 biosynthesis. The BAC clone pDA2002 was shown to
      harbor the complete A54145 biosynthesis gene cluster by heterologous expression
      in Streptomyces ambofaciens and Streptomyces roseosporus strains in yields of
      >100 mg/liter. S. fradiae mutants defective in LptI methyltransferase function
      were constructed, and they produced only A54145 factors containing glutamic acid
      (Glu12), at the expense of factors containing 3-methyl-glutamic acid (3mGlu12).
      This provided a practical route to produce high levels of pure Glu12-containing
      lipopeptides. A suite of mutant strains and plasmids was created for
      combinatorial biosynthesis efforts focused on modifying the A54145 peptide
      backbone to generate a compound with daptomycin antibacterial activity and
      activity in Streptococcus pneumoniae pulmonary infections.

PMID- 20802083
TI  - Engineered lactic acid bacterium Lactococcus lactis capable of binding antibodies
      and tumor necrosis factor alpha.
AB  - We have optimized the display of the B domain of staphylococcal protein A on the
      surface of Lactococcus lactis. The maximum binding capacity was estimated at
      0.146 MUg of antibody per 108 cells and was sustained at 86% after treatment with
      simulated gastric juice. A tumor necrosis factor alpha (TNF-alpha)-binding
      affibody was also displayed and bound TNF-alpha, which could be useful in the
      treatment of inflammatory bowel disease.

PMID- 20802084
TI  - Characterization of Lactococcus lactis phage 949 and comparison with other
      lactococcal phages.
AB  - The virulent Lactococcus lactis phage 949 was isolated in 1975 from cheese whey
      in New Zealand. This phage is a member of the Siphoviridae family and of a rare
      lactococcal phage group that bears its name (949 group). It has an icosahedral
      capsid (79-nm diameter) and a very long noncontractile tail (length, 500 nm;
      width, 12 nm). It infected 7 of 59 tested L. lactis strains, a somewhat expanded
      host range for a rare lactococcal phage. The abortive phage infection defense
      mechanisms AbiQ and AbiT strongly inhibited the multiplication of phage 949, but
      AbiK and AbiV did not. Its double-stranded DNA (dsDNA) genome of 114,768 bp is,
      to date, the largest among lactococcal phages. Its GC content was calculated at
      32.7%, which is the lowest reported for a lactococcal phage. Its 154 open reading
      frames (ORFs) share limited identity with database sequences. In addition,
      terminal redundancy was observed as well as the presence of six tRNAs, one group
      I intron, and putative recombinases. SDS-PAGE coupled with mass spectrometry
      identified 13 structural proteins. The genomes of the members of the 10 currently
      known L. lactis phage groups were used to construct a proteomic tree. Each L.
      lactis phage group separated into distinct genetic clusters, validating the
      current classification scheme. Of note, members of the polythetic P335 groups
      were clearly separated into subgroups.

PMID- 20802086
TI  - The effectiveness of a stimulation program on cognitive capacity among
      individuals older than 60.
AB  - The purpose of this study was to test the effects of a multistimulant home-based
      intervention program on cognitive function, anxiety, and depression among older
      adults with cognitive impairment. This research is quasi-experimental and was
      designed in an effort to increase the cognitive capacity of individuals above the
      age of 60 with reduced cognitive capacities. Each senior received a total of
      seven home visits, including intervention conversation, newspaper/ book reading,
      painting/handcraft activities, and physical exercise. The Mini Mental State Test
      scores of the participants statistically increased, whereas the Beck Anxiety and
      the Geriatric Depression Scale scores showed a decrease (p < .05) after the
      intervention. Findings demonstrate that the multistimulant approach to improve
      cognitive capacity among individuals older than 60 years was successful.

PMID- 20802085
TI  - Construction of a large extracellular protein interaction network and its
      resolution by spatiotemporal expression profiling.
AB  - Extracellular interactions involving both secreted and membrane-tethered receptor
      proteins are essential to initiate signaling pathways that orchestrate cellular
      behaviors within biological systems. Because of the biochemical properties of
      these proteins and their interactions, identifying novel extracellular
      interactions remains experimentally challenging. To address this, we have
      recently developed an assay, AVEXIS (avidity-based extracellular interaction
      screen) to detect low affinity extracellular interactions on a large scale and
      have begun to construct interaction networks between zebrafish receptors
      belonging to the immunoglobulin and leucine-rich repeat protein families to
      identify novel signaling pathways important for early development. Here, we
      expanded our zebrafish protein library to include other domain families and many
      more secreted proteins and performed our largest screen to date totaling 16,544
      potential unique interactions. We report 111 interactions of which 96 are novel
      and include the first documented extracellular ligands for 15 proteins. By
      including 77 interactions from previous screens, we assembled an expanded network
      of 188 extracellular interactions between 92 proteins and used it to show that
      secreted proteins have twice as many interaction partners as membrane-tethered
      receptors and that the connectivity of the extracellular network behaves as a
      power law. To try to understand the functional role of these interactions, we
      determined new expression patterns for 164 genes within our clone library by
      using whole embryo in situ hybridization at five key stages of zebrafish
      embryonic development. These expression data were integrated with the binding
      network to reveal where each interaction was likely to function within the embryo
      and were used to resolve the static interaction network into dynamic tissue- and
      stage-specific subnetworks within the developing zebrafish embryo. All these data
      were organized into a freely accessible on-line database called ARNIE (AVEXIS
      Receptor Network with Integrated Expression; www.sanger.ac.uk/arnie) and provide
      a valuable resource of new extracellular signaling interactions for developmental
      biology.

PMID- 20802088
TI  - Essential role of B7-H1 in double-stranded RNA-induced augmentation of an asthma
      phenotype in mice.
AB  - Clinical and epidemiological studies have shown the contribution of viral
      infection to the development of allergic asthma. Many RNA viruses, pathogenic for
      the respiratory tract, generate double-stranded (ds)RNA during their replication.
      Typical innate immune responses triggered by dsRNA involve the endosomal and
      cytoplasmic pathways. The former is mediated by Toll/IL-1R domain-containing
      adaptor inducing IFN-beta (TRIF), and the latter by IFN-beta promoter stimulator
      1 (IPS-1). We explored the effect of polyinocinic polycytidilic acid, a synthetic
      dsRNA, on the development of an asthma phenotype in mice. Administration of dsRNA
      during ovalbumin sensitization augmented airway eosinophilia and airway
      hyperresponsiveness after an antigen challenge, which was associated with
      enhanced induction of IL-13-producing CD8(+) T cells. The augmentation was
      induced in IPS-1-deficient mice but not in TRIF-deficient mice. The interactions
      between dendritic cells (DCs) and T cells are regulated by B7-family
      costimulatory molecules, including B7-H1 (also known as PD-L1), a putative ligand
      for programmed death-1 (PD-1). Treatment of bone marrow-derived DCs with dsRNA
      enhanced B7-H1 expression in a TRIF-dependent manner. Additionally, dsRNA
      increased B7-H1 expression on DCs in the draining lymph nodes of ovalbumin
      sensitized mice. The augmentation of the asthma phenotype was prevented by the
      treatment of mice with anti-B7-H1 mAb but not with anti-PD-1 mAb. The
      augmentation was not induced in B7-H1-deficient mice. These results suggest that
      dsRNA-triggered activation of the innate immune system in sensitization leads to
      augmentation of the asthma phenotype via IL-13 mainly from CD8(+) T cells. B7-H1
      plays a crucial role in the process without requiring interaction with PD-1.

PMID- 20802087
TI  - Effect of cocaine on human immunodeficiency virus-mediated pulmonary endothelial
      and smooth muscle dysfunction.
AB  - Human immunodeficiency virus (HIV)-associated pulmonary arterial hypertension
      (PAH) is a devastating, noninfectious complication of acquired immune deficiency
      syndrome, and the majority of HIV-PAH cases occur in individuals with a history
      of intravenous drug use (IVDU). However, although HIV-1 and IVDU have been
      associated with PAH independently or in combination, the pathogenesis of the
      disproportionate presence of HIV-PAH in association with IVDU has yet to be
      characterized. The objective of this study was to obtain a better understanding
      of the interactions between HIV-1 and cocaine to help uncover the mechanism(s) of
      the development of HIV-PAH. We observed that exposure of HIV-infected macrophages
      or HIV-Trans-Activator of Transcription (Tat)-treated pulmonary endothelial cells
      to cocaine enhanced the expression of platelet-derived growth factor (PDGF)-BB.
      Simultaneous treatment with Tat and cocaine, on the other hand, exacerbated both
      the disruption of tight junction proteins (TJPs), with enhanced permeability in
      pulmonary endothelial cells, and the proliferation of pulmonary smooth muscle
      cells (pSMCs) compared with either treatment alone. Histological examination of
      HIV plus IVDU human lung sections showed signs of early pulmonary arteriopathy,
      severe down-modulation of TJPs, and increased expression of PDGF-BB compared with
      the lung sections from individuals who are infected with HIV and without history
      of IVDU. Interestingly, blocking of PDGF receptor signaling with the receptor
      antagonist or small interfering RNA has been shown to inhibit the increase in
      proliferation of pSMCs on Tat and cocaine exposure. Our results, therefore,
      support an additive effect of cocaine to HIV infection in the development of
      pulmonary arteriopathy through enhancement of endothelial dysfunction and
      proliferation of pSMCs, while also suggesting PDGF-PDGF receptor axis as a
      potential target for use in clinical intervention.

PMID- 20802089
TI  - Computational analysis of genome-wide DNA methylation during the differentiation
      of human embryonic stem cells along the endodermal lineage.
AB  - The generation of genome-wide data derived from methylated DNA
      immunoprecipitation followed by sequencing (MeDIP-seq) has become a major tool
      for epigenetic studies in health and disease. The computational analysis of such
      data, however, still falls short on accuracy, sensitivity, and speed. We propose
      a time-efficient statistical method that is able to cope with the inherent
      complexity of MeDIP-seq data with similar performance compared with existing
      methods. In order to demonstrate the computational approach, we have analyzed
      alterations in DNA methylation during the differentiation of human embryonic stem
      cells (hESCs) to definitive endoderm. We show improved correlation of normalized
      MeDIP-seq data in comparison to available whole-genome bisulfite sequencing data,
      and investigated the effect of differential methylation on gene expression.
      Furthermore, we analyzed the interplay between DNA methylation, histone
      modifications, and transcription factor binding and show that in contrast to de
      novo methylation, demethylation is mainly associated with regions of low CpG
      densities.

PMID- 20802090
TI  - Physical temperature effects on trust behavior: the role of insula.
AB  - Trust lies at the heart of person perception and interpersonal decision making.
      In two studies, we investigated physical temperature as one factor that can
      influence human trust behavior, and the insula as a possible neural substrate.
      Participants briefly touched either a cold or warm pack, and then played an
      economic trust game. Those primed with cold invested less with an anonymous
      partner, revealing lesser interpersonal trust, as compared to those who touched a
      warm pack. In Study 2, we examined neural activity during trust-related processes
      after a temperature manipulation using functional magnetic resonance imaging. The
      left-anterior insular region activated more strongly than baseline only when the
      trust decision was preceded by touching a cold pack, and not a warm pack. In
      addition, greater activation within bilateral insula was identified during the
      decision phase followed by a cold manipulation, contrasted to warm. These results
      suggest that the insula may be a key shared neural substrate that mediates the
      influence of temperature on trust processes.

PMID- 20802092
TI  - Platelet-rich plasma releasate promotes differentiation of tendon stem cells into
      active tenocytes.
AB  - BACKGROUND: Platelet-rich plasma (PRP) has been used to enhance tendon healing in
      clinical settings. However, the cellular mechanisms underlying PRP treatment of
      injured tendons remain unclear. The aim of this study was to determine the
      effects of PRP, in the form of PRP-clot releasate (PRCR), on tendon stem cells
      (TSCs), a newly discovered cell population in tendons. HYPOTHESIS: The PRCR
      treatment promotes differentiation of TSCs into tenocytes that are activated to
      proliferate quickly and increase collagen production. STUDY DESIGN: Controlled
      laboratory study. METHODS: After PRCR treatment, cell morphology, expression of
      stem/progenitor cell marker nucleostemin, and population doubling time were
      examined. In addition, gene and protein analyses were performed using reverse
      transcription-polymerase chain reaction, immunocytochemistry, and Western blot to
      characterize the type of cells that had differentiated after PRCR treatment.
      RESULTS: The TSCs without PRCR treatment were small and exhibited an irregular
      shape, whereas with increasing PRCR dosage, TSCs became large, well spread, and
      highly elongated with downregulation of nucleostemin expression. The PRCR
      treatment also markedly enhanced TSC proliferation, tenocyte-related gene and
      protein expression, and total collagen production, all of which indicated that
      PRCR treatment induced differentiation of TSCs into activated tenocytes.
      CONCLUSION: The PRCR treatment promotes differentiation of TSCs into active
      tenocytes exhibiting high proliferation rates and collagen production capability.
      CLINICAL RELEVANCE: The findings of this study suggest that PRP treatment of
      injured tendons is "safe" as it promotes TSC differentiation into tenocytes
      rather than nontenocytes, which would compromise the structure and function of
      healing tendons by formation of nontendinous tissues. Moreover, they suggest that
      PRP treatment can enhance tendon healing because tenocytes induced to
      differentiate by PRP are activated to proliferate quickly and produce abundant
      collagen to repair injured tendons that have lost cells and matrix.

PMID- 20802091
TI  - Contrasting patterns of language-associated brain activity in autism and Williams
      syndrome.
AB  - Two neurodevelopmental disorders, Williams syndrome (WS) and autism, are both
      commonly described as having opposite social profiles: social avoidance in autism
      vs hypersociability in individuals with WS. The goal of this study was to
      contrast the brain activity associated with language processing in these two
      populations, in order to understand the very likely interplay between the use of
      language and the sociability dimension, on which these disorders diverge. Towards
      this aim, the N400 component of the event-related potentials was used to quantify
      the processing of semantic integration in these two populations. Results revealed
      that individuals with WS showed a significantly larger N400 effect, as compared
      to both typical controls and individuals with autism, while the latter group
      demonstrated the smallest N400 effect. The findings demonstrate quite opposite
      profiles of neural correlates of language processing in WS and autism, mirroring
      their contrasting social phenotypes.

PMID- 20802093
TI  - Less-invasive reconstruction of chronic achilles tendon ruptures using a peroneus
      brevis tendon transfer.
AB  - BACKGROUND: A less-invasive technique to reconstruct chronic Achilles tendon
      rupture with transfer of the tendon of peroneus brevis is suitable in patients
      with a tendon gap less than 6 cm. PURPOSE: To report the results of a
      longitudinal study on reconstruction of chronic Achilles tendon rupture using a
      less-invasive peroneus brevis repair through 2 paramidline incisions. STUDY
      DESIGN: Case series; Level of evidence, 4. METHODS: Thirty-two patients underwent
      surgery for chronic Achilles tendon rupture with a tendon gap during surgery less
      than 6 cm, occurring between 60 days and 9 months preoperatively. All
      participants were prospectively followed for 5 to 8 years; final review was
      performed at 48.4 +/- 13.5 months from the operation. Clinical and functional
      assessment (anthropometric measurements, isometric strength, postoperative
      Achilles tendon total rupture score) was performed. RESULTS: All patients were
      able to walk on tiptoes, and no patient used a heel lift or walked with a visible
      limp. No patient developed a clinically evident deep vein thrombosis or sustained
      a rerupture. Five patients were managed nonoperatively after a superficial
      infection of one of the surgical wounds. At final review, the maximum calf
      circumference remained significantly decreased in the operated leg (39.2 +/- 6.2
      cm [side with rupture] vs 40.9 +/- 7.0 cm [uninjured side]; P = .04). The
      operated limb was significantly less strong than the nonoperated one (231.2 +/-
      132.4 N vs 275.3 +/- 150.2 N; P = .033). The Achilles tendon total rupture score
      at final follow-up was 92.5 +/- 14.2. CONCLUSION: The management of chronic
      Achilles tendon tears by a less-invasive peroneus brevis repair is technically
      demanding but safe. It allows good recovery, even in patients with a chronic
      rupture of 9 months' duration. These patients should be warned that they are at
      risk for postoperative complications and that their ankle plantar flexion
      strength is likely to be reduced.

PMID- 20802094
TI  - Acute achilles tendon rupture: a randomized, controlled study comparing surgical
      and nonsurgical treatments using validated outcome measures.
AB  - BACKGROUND: There is no consensus regarding the optimal treatment for patients
      with acute Achilles tendon rupture. Few randomized controlled studies have
      compared outcomes after surgical or nonsurgical treatment with both groups
      receiving early mobilization. PURPOSE: This study was undertaken to compare
      outcomes of patients with acute Achilles tendon rupture treated with or without
      surgery using early mobilization and identical rehabilitation protocols. STUDY
      DESIGN: Randomized, controlled trial; Level of evidence, 1. METHODS: Ninety-seven
      patients (79 men, 18 women; mean age, 41 years) with acute Achilles tendon
      rupture were treated and followed for 1 year. The primary end point was
      rerupturing. Patients were evaluated using the Achilles tendon Total Rupture
      Score (ATRS), functional tests, and clinical examination at 6 and 12 months after
      injury. RESULTS: There were 6 (12%) reruptures in the nonsurgical group and 2
      (4%) in the surgical group (P = .377). The mean 6- and 12-month ATRS were 72 and
      88 points in the surgical group and 71 and 86 points in the nonsurgical group,
      respectively. Improvements in ATRS between 6 and 12 months were significant for
      both groups, with no significant between-group differences. At the 6-month
      evaluation, the surgical group had better results compared with the nonsurgically
      treated group in some of the muscle function tests; however, at the 12-month
      evaluation there were no differences between the 2 groups except for the heel
      rise work test in favor of the surgical group. At the 12-month follow-up, the
      level of function of the injured leg remained significantly lower than that of
      the uninjured leg in both groups. CONCLUSION: The results of this study did not
      demonstrate any statistically significant difference between surgical and
      nonsurgical treatment. Furthermore, the study suggests that early mobilization is
      beneficial for patients with acute Achilles tendon rupture whether they are
      treated surgically or nonsurgically. The preferred treatment strategy for
      patients with acute Achilles tendon rupture remains a subject of debate. Although
      the study met the sample size dictated by the authors' a priori power
      calculation, the difference in the rerupture rate might be considered clinically
      important by some.

PMID- 20802095
TI  - Cholesteryl ester transfer protein antagonism by drugs--a poor choice.

PMID- 20802096
TI  - A new assay for measurement of the liberated domain I of the urokinase receptor
      in plasma improves the prediction of survival in colorectal cancer.
AB  - BACKGROUND: The liberated domain I of the urokinase plasminogen activator
      receptor [uPAR(I)] is a significant prognostic marker in lung and ovarian cancer,
      although the uPAR(I) concentration is below the limit of quantification (LOQ) in
      a substantial proportion of patient samples (Lung Cancer 2005;48:349-55; Clin
      Cancer Res 2008;14:5785-93; APMIS 2009;117:755-61). This study was undertaken to
      design an immunoassay with improved functional sensitivity for measuring uPAR(I)
      and to evaluate the prognostic value of uPAR(I) for colorectal cancer (CRC)
      patients. METHODS: Surface plasmon resonance analysis identified 2 monoclonal
      antibodies, R3 and R20, that simultaneously bind to the liberated uPAR(I) but not
      to intact uPAR. We used R3 for capture and Eu-labeled R20 for detection in
      designing a 2-site sandwich time-resolved fluorescence immunoassay (TR-FIA 4) for
      measuring liberated uPAR(I). TR-FIA 4 was validated for use with citrated plasma.
      The prognostic value of the uPAR(I) concentration was evaluated in 298 CRC
      patients. The Cox proportional hazards model was used for the uni- and
      multivariate survival analyses. RESULTS: The LOQ was 0.65 pmol/L. Liberated
      uPAR(I) was measurable in all patient samples with TR-FIA 4. In the multivariate
      analysis that included sex, age, tumor stage, tumor localization, and adjuvant
      treatment, the uPAR(I) concentration measured with TR-FIA 4 (hazard ratio, 1.72;
      95% CI, 1.15-2.57; P = 0.009), as well as the concentration of intact soluble
      uPAR plus the cleaved uPAR fragment containing domains II and III, tumor stage,
      and age were independent predictors of prognosis. CONCLUSIONS: TR-FIA 4 has a
      functional sensitivity improved 4-fold over that of the previous uPAR(I) assay.
      The uPAR(I) concentration measured with TR-FIA 4 is an independent predictor of
      prognosis in CRC patients.

PMID- 20802097
TI  - Nanotechnology: improving clinical testing?

PMID- 20802098
TI  - A healthy young man presenting with multiple rib fractures.

PMID- 20802099
TI  - Commentary.

PMID- 20802100
TI  - Commentary.

PMID- 20802103
TI  - A 67-year-old woman with a systemic inflammatory syndrome and sicca.

PMID- 20802101
TI  - Intrapersonal and populational heterogeneity of the chemokine RANTES.
AB  - BACKGROUND: Current immunoassays for the chemokine RANTES (regulated on
      activation, normal T-cell expressed and secreted) are not tailored for specific
      isoforms that exist endogenously, despite the fact that variants with modified
      activity are known to exist. This is surprising in view of this protein's
      ubiquitous increased presence in many diseases and that the 2 established
      isoforms are truncated by enzymes also correlated to disease. An in-depth
      population survey of RANTES heterogeneity in the context of multiple diseases via
      a mass spectrometric immunoassay (MSIA) may resolve this issue. METHODS: We
      developed an MSIA for RANTES and endogenous variants apparent in human plasma.
      Samples from multiple cohorts of individuals (type 2 diabetes, congestive heart
      failure, history of myocardial infarction, and cancer patients) were run in
      parallel with samples from healthy individuals (239 people total). We used 230
      microL of plasma per individual and tabulated relative percent abundance (RPA)
      values for identified isoforms. RESULTS: We detected at least 19 variants,
      including the dipeptidyl peptidase IV (DPP-IV)-truncated variant. The majority of
      variants were unreported in the literature. Identifiable modifications included N
      and/or C-terminal truncations, oxidation, glycation, and glycosylation. We
      observed statistically significant differences in RPA values for multiple
      variants between disease cohorts and recognized prospective disease-specific
      protein profiles for RANTES. CONCLUSIONS: Because of widespread interest in the
      clinical value of RANTES, the protein diversity established here may aid in the
      design of future, fully quantitative assays. Equally important, an inclusive
      qualitative understanding of RANTES heterogeneity may present new insights into
      the relationship between RANTES and disease.

PMID- 20802105
TI  - Receptor activity modifying protein-3 mediates the protumorigenic activity of
      lysyl oxidase-like protein-2.
AB  - Lysyl oxidase-like protein-2 (LOXL2) induces epithelial to mesenchymal transition
      and promotes invasiveness. To understand the mechanisms involved, we examined the
      effect of LOXL2 overexpression in MCF-7 cells on gene expression. We found that
      LOXL2 up-regulated the expression of receptor activity modifying protein-3
      (RAMP3). Expression of RAMP3 in MDA-MB-231 cells in which LOXL2 expression was
      inhibited restored vimentin expression, invasiveness, and tumor development.
      Inhibition of RAMP3 expression in MDA-MB-231 cells mimicked the effects produced
      by inhibition of LOXL2 expression and was accompanied by inhibition of p38
      phosphorylation. LOXL2 overexpression in these cells did not restore
      invasiveness, suggesting that RAMP3 functions downstream to LOXL2. LOXL2 and
      RAMP3 are strongly coexpressed in human colon, breast, and gastric carcinomas but
      not in normal colon or gastric epithelial cells. RAMP3 associates with several G
      protein-coupled receptors forming receptors for peptides, such as adrenomedullin
      and amylin. We hypothesized that RAMP3 could function as a transducer of
      autocrine signals induced by such peptides. However, the proinvasive effects of
      RAMP3 could not be abrogated following inhibition of the expression or activity
      of these peptides. Our experiments suggest that the protumorigenic effects of
      LOXL2 are partially mediated by RAMP3 and that RAMP3 inhibitors may function as
      antitumorigenic agents. -

PMID- 20802106
TI  - The adverse effects of obesity on reproduction.

PMID- 20802108
TI  - A somewhat neglected aspect of insect neurophysiology.

PMID- 20802109
TI  - Catecholamines, cardiac natriuretic peptides and chromogranin A: evolution and
      physiopathology of a 'whip-brake' system of the endocrine heart.
AB  - In the past 50 years, extensive evidence has shown the ability of vertebrate
      cardiac non-neuronal cells to synthesize and release catecholamines (CA). This
      formed the mindset behind the search for the intrinsic endocrine heart
      properties, culminating in 1981 with the discovery of the natriuretic peptides
      (NP). CA and NP, co-existing in the endocrine secretion granules and acting as
      major cardiovascular regulators in health and disease, have become of great
      biomedical relevance for their potent diagnostic and therapeutic use. The concept
      of the endocrine heart was later enriched by the identification of a growing
      number of cardiac hormonal substances involved in organ modulation under normal
      and stress-induced conditions. Recently, chromogranin A (CgA), a major
      constituent of the secretory granules, and its derived cardio-suppressive and
      antiadrenergic peptides, vasostatin-1 and catestatin, were shown as new players
      in this framework, functioning as cardiac counter-regulators in 'zero steady
      state error' homeostasis, particularly under intense excitatory stimuli, e.g. CA
      induced myocardial stress. Here, we present evidence for the hypothesis that is
      gaining support, particularly among human cardiologists. The actions of CA, NP
      and CgA, we argue, may be viewed as a hallmark of the cardiac capacity to
      organize 'whip-brake' connection-integration processes in spatio-temporal
      networks. The involvement of the nitric oxide synthase (NOS)/nitric oxide (NO)
      system in this configuration is discussed. The use of fish and amphibian
      paradigms will illustrate the ways that incipient endocrine-humoral agents have
      evolved as components of cardiac molecular loops and important intermediates
      during evolutionary transitions, or in a distinct phylogenetic lineage, or under
      stress challenges. This may help to grasp the old evolutionary roots of these
      intracardiac endocrine/paracrine networks and how they have evolved from
      relatively less complicated designs. The latter can also be used as an
      intellectual tool to disentangle the experimental complexity of the mammalian and
      human endocrine hearts, suggesting future investigational avenues.

PMID- 20802107
TI  - Obesity and the pubertal transition in girls and boys.
AB  - Childhood obesity has become a major health concern in recent decades, especially
      with regard to metabolic abnormalities that impart a high risk for future
      cardiovascular disease. Recent data suggest that excess adiposity during
      childhood may influence pubertal development as well. In particular, excess
      adiposity during childhood may advance puberty in girls and delay puberty in
      boys. Obesity in peripubertal girls may also be associated with hyperandrogenemia
      and a high risk of adolescent polycystic ovary syndrome. How obesity may perturb
      various hormonal aspects of pubertal development remains unclear, but potential
      mechanisms are discussed herein. Insulin resistance and compensatory
      hyperinsulinemia may represent a common thread contributing to many of the
      pubertal changes reported to occur with childhood obesity. Our understanding of
      obesity's impact on pubertal development is in its infancy, and more research
      into pathophysiological mechanisms and longer-term sequelae is important.

PMID- 20802110
TI  - Single source sound production and dynamic beam formation in echolocating harbour
      porpoises (Phocoena phocoena).
AB  - Echolocating toothed whales produce high-powered clicks by pneumatic actuation of
      phonic lips in their nasal complexes. All non-physeteroid toothed whales have two
      pairs of phonic lips allowing many of these species to produce both whistles and
      clicks at the same time. That has led to the hypothesis that toothed whales can
      increase the power outputs and bandwidths of clicks, and enable fast clicking and
      beam steering by acutely timed actuation of both phonic lip pairs simultaneously.
      Here we test that hypothesis by applying suction cup hydrophones on the sound
      producing nasal complexes of three echolocating porpoises (Phocoena phocoena)
      with symmetrical pairs of phonic lips. Using time of arrival differences on three
      hydrophones, we show that all recorded clicks from these three porpoises are
      produced by the right pair of phonic lips with no evidence of simultaneous or
      independent actuation of the left pair. It is demonstrated that porpoises,
      despite actuation of only one sound source, can change their output and sound
      beam probably through conformation changes in the sound-producing soft tissues
      and nasal sacs, and that the coupling of the phonic lips and the melon acts as a
      waveguide for sound energy between 100 and 160 kHz to generate a forward-directed
      sound beam for echolocation.

PMID- 20802111
TI  - The orientation-dependent visual spatial cut-off frequency in a spider.
AB  - Cupiennius salei (Araneae, Ctenidae) has, like most spiders, eight camera-type
      eyes. The anterior median eyes are called principal eyes and have a movable
      retina; all of the other eyes are referred to as secondary eyes and are equipped
      with a reflecting tapetum. The photoreceptors in the secondary eyes are arranged
      in rows on the tapetum and the inter-receptor angle along such a row is smaller
      than normal to it. In this study, the vertical and horizontal spatial cut-off
      frequencies of moving gratings were measured for the posterior median (PM) eyes,
      and the data were then compared with the anatomical data reported in the
      literature. Detection of moving objects in the secondary eyes enhances the eye
      muscle potential frequency in the principal eyes. We thus recorded the eye muscle
      activity with a telemetric unit as a monitor for motion detection while moving
      stimuli - sinusoidally modulated bright and dark stripes - were presented to the
      PM eyes on a computer screen. A significant increase in the eye muscle activity
      was measured for gratings at an angular wavelength of 2.0 deg in the vertical
      orientation and of 2.7 deg in the horizontal direction. In the vertical
      orientation the critical wavelength is twice the inter-receptor angle; in the
      horizontal orientation the spiders responded to wavelengths that are smaller than
      twice the corresponding inter-receptor angle. The cut-off frequency seems thus to
      be limited by the visual field of the photoreceptors rather than the inter
      receptor angle. The relative intensity modulations modelled for the two different
      grating orientations in single photoreceptor cells were in line with our data.

PMID- 20802112
TI  - Sympathetic, parasympathetic and enteric regulation of the gastrointestinal
      vasculature in rainbow trout (Oncorhynchus mykiss) under normal and postprandial
      conditions.
AB  - The control of the gastrointestinal hyperemia that occurs after feeding in most
      animals is of fundamental importance for the subsequent absorption, metabolism
      and redistribution of nutrients. Yet, in fish, it has received little attention
      and the nature of it is far from clear. We sought to investigate the importance
      of extrinsic and intrinsic innervation of the gastrointestinal tract in the
      regulation of gastrointestinal blood flow in rainbow trout (Oncorhynchus mykiss).
      The contribution of the extrinsic innervation, i.e. by the sympathetic and the
      parasympathetic nervous system, was examined by comparing the response to the
      injection of a predigested nutrient diet into the proximal intestine of untreated
      fish with the response in fish in which the splanchnic and vagal innervation of
      the gut had been removed. We also injected the predigested nutrient diet into
      anaesthetized fish treated with tetrodotoxin that would block the intrinsic
      innervation of the gut (i.e. enteric nervous system). Our results confirm the
      notion that the sympathetic portion of the extrinsic innervation maintains the
      basal vascular tone, but neither the splanchnic nor the vagal innervation is
      fundamental to the postprandial hyperemia. However, the tetrodotoxin treatment
      completely abolished the postprandial hyperemia, indicating the importance of the
      enteric nervous system. In conclusion, it seems as though the enteric nervous
      system is essential to the regulation of the postprandial hyperemia, and that the
      extrinsic innervation is involved mainly in the regulation of gastrointestinal
      blood flow under normal conditions and in response to central coordination with
      other organs.

PMID- 20802113
TI  - Yolk testosterone shapes the expression of a melanin-based signal in great tits:
      an antioxidant-mediated mechanism?
AB  - Conspicuous traits produced by melanin deposition in integuments are often
      involved in visual communication. The information content of melanin-based
      signals is unclear as their expression is tightly controlled by genes and,
      apparently, is less dependent on individual condition. In birds, high
      heritabilities have been attributed to melanin-based plumages, often on the basis
      of egg-swapping manipulations (cross-fostering experiments). However, it is well
      known that female birds can differentially transfer testosterone to the egg yolk.
      Furthermore, high testosterone levels have been related to high oxidative stress.
      As we recently found that oxidative stress experienced during development
      influences the expression of melanin-based traits, here we manipulated the level
      of yolk testosterone in great tits (Parus major) to assess the influence of this
      maternal effect on the expression of the black breast stripe, a well-known
      melanin-based signal. We predicted that fledglings hatched from eggs with high
      testosterone levels will not only show larger black stripes but also experience
      changes in their antioxidant machinery. Indeed, the size of the black stripe of
      great tits hatched from testosterone-injected eggs was almost double that of
      controls. Furthermore, the same individuals showed a trend to higher levels of
      circulating antioxidants, which suggests an adaptive response against some
      testosterone-induced oxidative challenge.

PMID- 20802114
TI  - Are fish less responsive to a flow stimulus when swimming?
AB  - Fish use the lateral line system to sense the water flow created by a predator's
      strike. Despite its potential importance to the survival of a diversity of
      species, it is unclear whether this ability becomes compromised when a fish
      swims. Therefore, the present study compared the behavioral responsiveness of
      swimming and motionless zebrafish (Danio rerio) larvae when exposed to the flow
      of a suction-feeding predator. This flow was generated with an impulse chamber,
      which is a device that we developed to generate a repeatable stimulus with a
      computer-controlled servo motor. Using high-speed video recordings, we found that
      about three-quarters (0.76, N=121) of motionless larvae responded to the stimulus
      with an escape response. These larvae were 66% more likely to respond to flow
      directed perpendicular than flow running parallel to the body. Swimming larvae
      exhibited a 0.40 response probability and were therefore nearly half as likely to
      respond to flow as motionless larvae. However, the latency between stimulus and
      response was unaffected by swimming or the direction of flow. Therefore, swimming
      creates changes in the hydrodynamics or neurophysiology of a larval fish that
      diminish the probability, but not the speed, of their response to a flow
      stimulus. These findings demonstrate a sensory benefit to the intermittent
      swimming behavior observed among a broad diversity of fishes.

PMID- 20802115
TI  - Audiogram of a formerly stranded long-finned pilot whale (Globicephala melas)
      measured using auditory evoked potentials.
AB  - Long-finned pilot whales are highly social odontocetes found in temperate and
      subpolar regions. This species is particularly known for its interaction with
      fisheries as well as its mass strandings. Recent tagging work has provided some
      information about pilot whales in the wild but, even though they have been
      successfully kept in captivity, little is known about their sensory capabilities.
      This study investigates the hearing abilities of a rehabilitated 2 year old male
      long-finned pilot whale. A complete audiogram was collected using auditory evoked
      potential techniques that included measurements of nine frequencies from 4 to 100
      kHz presented as sinusoidally amplitude-modulated tones. The results indicated
      that the region of best hearing was between 11.2 and 50 kHz and the subject had
      relatively poor high frequency hearing compared with other odontocete species.
      This study emphasizes the importance of collecting basic hearing measurements
      from new species, understanding diagnostic life histories as well as continuously
      increasing the sample size of audiometry measurements within and between
      odontocete species as animals become available.

PMID- 20802116
TI  - Effects of tentacle amputation and regeneration on the morphology and activity of
      the olfactory center of the terrestrial slug Limax valentianus.
AB  - The tentacles of pulmonates regenerate spontaneously following amputation. The
      regenerated tentacle is equipped with all the elements necessary for normal
      olfactory functioning, and the slugs can behave as well as they did before the
      tentacle amputation. However, it is not known what changes occur to the olfactory
      center procerebrum in the brain at the morphological and physiological levels.
      Here, we investigated the innervation of tentacular nerves into the procerebrum
      by examining the size of the terminal mass (input layer from tentacular nerves)
      of the procerebrum and also by staining afferent nerves immunohistochemically at
      15, 58 and 75 days following unilateral amputation of the superior and inferior
      tentacles. The size of the terminal mass was significantly decreased, and the Phe
      Met-Arg-Phe-NH(2)ergic (FMRFamidergic) afferent nerves disappeared by 15 days
      following the tentacle amputation. However, the size of the terminal mass had
      recovered substantially by 58 days, as the tentacle regenerated. The
      FMRFamidergic innervation into the cerebral ganglion was also restored by this
      time. An extended recovery (75 days), however, did not result in any further
      increase in the size of the terminal mass. We also recorded the local field
      potential (LFP) oscillation in the procerebrum. We found that the oscillatory
      frequency of the LFP had decreased at 15 days following the tentacle amputation
      but had recovered at 58 and 75 days. These results suggest that the amputation
      and regrowth of the tentacle are accompanied by the respective degeneration and
      re-innervation of olfactory nerves, and these changes in the innervation status
      affect the basal state of LFP oscillation.

PMID- 20802117
TI  - Rh glycoprotein expression is modulated in pufferfish (Takifugu rubripes) during
      high environmental ammonia exposure.
AB  - Rhesus (Rh) protein involvement in ammonia transport processes in freshwater fish
      has received considerable attention; however, parallel investigations in seawater
      species are scant. We exposed pufferfish to high environmental ammonia (HEA; 1
      and 5 mmol l(-1) NH(4)HCO(3)) and evaluated the patterns of ammonia excretion and
      gill Rh mRNA and protein expression. Gill H(+)-ATPase, NHE1, NHE2, NHE3,
      Na(+)/K(+)-ATPase (NKA), Na(+)/K(+)/2Cl(-) co-transporter (NKCC1) mRNA, H(+)
      ATPase activity, NKA protein and activity, were also quantified. Activation of
      NKA by NH(4)(+) was demonstrated in vitro. The downregulation of Rhbg mRNA and
      simultaneous upregulations of Rhcg1, H(+)-ATPase, NHE3, NKA, NKCC1 mRNA, H(+)
      ATPase activity, and NKA protein and activity levels suggested that during HEA,
      ammonia excretion was mediated mainly by mitochondria-rich cells (MRCs) driven by
      NKA with basolateral NH(4)(+) entry via NKA and/or NKCC1, and apical NH(3)
      extrusion via Rhcg1. Reprotonation of NH(3) by NHE3 and/or H(+)-ATPase would
      minimise back flux through the Rh channels. Downregulated Rhbg and Rhag mRNA
      observed in the gill during HEA suggests a coordinated protective response to
      minimise the influx of external ammonia via the pavement cells and pillar cells,
      respectively, while routing ammonia excretion through the MRCs. Exposure to
      hypercapnia (1% CO(2) in air) resulted in downregulated gill and erythrocyte Rhag
      mRNA. Surprisingly, Rhag, Rhbg, Rhcg1 and Rhcg2 proteins responded to both
      hypercapnia and HEA with changes in their apparent molecular masses. A dual
      NH(3)/CO(2) transport function of the pufferfish Rh proteins is therefore
      suggested. The results support and extend an earlier proposed model of pufferfish
      gill ammonia excretion that was based on immunolocalisation of the Rh proteins.
      Passive processes and/or Rhbg and Rhcg2 in the pavement cells may maintain basal
      levels of plasma ammonia but elevated levels may require active excretion via NKA
      and Rhcg1 in the MRCs.

PMID- 20802118
TI  - Lymph flux rates from various lymph sacs in the cane toad Rhinella marina: an
      experimental evaluation of the roles of compliance, skeletal muscles and the
      lungs in the movement of lymph.
AB  - A new method for quantitatively determining lymph flux from various lymphatic
      sacs of an anuran, the cane toad, was developed. This method used the dye
      dilution principle of C(i)V(i)=C(f)V(f) following injection of Evans Blue into
      specific lymph sacs and measuring its appearance in the venous circulation. The
      apparent lymph volume was 57 ml kg(-1). The greatest rate of lymph return (0.5
      0.8 ml kg(-1) min(-1)) and best linear fit of Evans Blue appearance in the
      circulation with time followed injections into the subvertebral lymph sac, which
      has direct connections to both the anterior and posterior pairs of lymphatic
      hearts. Rate of lymph flux from the pair of posterior lymph hearts was three
      times greater than the anterior pair. Rates of lymph flux were only influenced by
      injection volume in the crural lymph sacs, implicating lymph sac compliance as
      the source of the pressure for lymph movement from these sacs. Femoral lymph sac
      fluxes were decreased by 60% following ablation of the tendons of the sphincter
      ani cloacalis, abdominal crenators and piriformis. This supports a role for these
      muscles in generating the pressure for vertical lymph movement. Femoral lymph sac
      fluxes were also decreased by 70% by the insertion of a coil in the subvertebral
      lymph sac, preventing normal compression and expansion of this sac by the lungs.
      This supports a role for lung ventilation in generating the pressure for vertical
      movement of lymph. Contrary to previous hypotheses, fluxes from the brachial sac
      were not influenced by insertion of the coil into the subvertebral sac. A
      haemorrhage equivalent to 50% of the blood volume did not change lymph flux rates
      from the femoral lymph sacs. These data provide the first experimental evidence
      that actual lymph fluxes in the cane toad Rhinella marina depend on lymph sac
      compliance, contraction of specific skeletal muscles and lung ventilation to move
      lymph laterally and vertically to the dorsally located lymphatic hearts.

PMID- 20802119
TI  - AMP-activated protein kinase controls metabolism and heat production during
      embryonic development in birds.
AB  - During embryonic and early juvenile development, endotherms must balance energy
      allocation between growth and heat production. Failure to either match the ATP
      demand of growing tissue or produce heat at the correct developmental stage will
      lead to damage of the organism. We tested the hypothesis that AMP-activated
      protein kinase (AMPK) is involved in the regulation of energy metabolism and heat
      production during development in the chicken (Gallus gallus). We show that mRNA
      concentrations of regulatory and catalytic AMPK subunits, AMPK total protein, and
      AMPK phosphorylation increase during development [3 days (-3 days) and one day (
      1 day) before hatching, and +1 day and +8 days after hatching] in liver, and to a
      lesser extent in skeletal muscle. Chronic stimulation with 5-aminoimidazole-4
      carboxamide-1-beta-D-ribofuranoside (AICAR) significantly increases AMPK
      phosphorylation in skeletal muscle and in liver. This increase was paralleled by
      significant increases in heat production, glucose utilization, and liver and
      skeletal muscle mitochondrial capacity (citrate synthase activity). The effects
      of AMPK are likely to be mediated by inhibition of acetyl CoA carboxylase (ACC)
      after hatching, when ACC protein concentration increases significantly, and by a
      significant AMPK-induced increase in PGC-1alpha mRNA concentration (at +1 day),
      but not in NRF-1 mRNA concentration. AMPK phosphorylation is under the control of
      thyroid hormone, and AMPK phosphorylation decreases significantly following the
      induction of hypothyroidism. We propose AMPK as a principal regulatory mechanism
      during the transition from ectothermy to endothermy in birds, and show that AMPK
      function in birds is similar to that observed in mammals.

PMID- 20802120
TI  - Innate olfactory preferences in dung beetles.
AB  - The effects of insect larval diet on adult olfactory responses to host-plant or
      food volatiles are still debated. The induction of adult host preferences has
      been studied in insects with diverse ecologies, including parasitoids, flower
      visitors and phytophagous species. We investigated this question for the first
      time in a coprophagous insect species. Larvae of the French scarab dung beetle
      Agrilinus constans were reared on four different artificial substrates containing
      dung from cattle, horse, sheep or wild boar, and responses of imagos to dung
      volatiles were then behaviourally tested in an olfactometer. We also reported the
      first analysis of the composition of different mammal dung volatiles. We showed
      that adult beetles were more attracted to cattle and sheep dung odours, and that
      larval feeding experience had no effect on the adult olfactory responses to dung
      volatiles. A second experiment showed that the presence of other insects inside
      the dung resource affects the process of dung selection by adults. We identified
      64 chemical compounds from dung emissions, and showed that dung volatiles clearly
      differed among different mammal species, allowing olfactory discrimination by
      dung beetles. Our results suggest that resource selection in coprophagous insects
      may be based on innate olfactory preferences. Further experiments should examine
      whether Agrilinus adults can learn new dung odours, and whether larval diet may
      influence the behaviour of adults in other coprophagous species.

PMID- 20802121
TI  - Spectral and polarization sensitivity of juvenile Atlantic salmon (Salmo salar):
      phylogenetic considerations.
AB  - We were interested in comparing the characteristics of polarization sensitivity
      in Atlantic salmon to those in Pacific salmon. Here we show that the common
      ancestor to the clade containing Salmo salar, Oncorhynchus mykiss, O. nerka, O.
      clarkii and Salvelinus fontinalis has the trait of ultraviolet polarization
      sensitivity. We examined spectral and polarization sensitivity of juvenile
      Atlantic salmon (Salmo salar) using both optic nerve compound action potential
      (CAP) and electroretinogram (ERG) recordings. Our experiments employed photic
      manipulation to adjust the sensitivity of the four cone mechanisms of Atlantic
      salmon. A spectrally broad background was used to ensure a contribution of all
      cone mechanisms to both spectral and polarization sensitivity. Chromatic
      adaptation was used to isolate the sensitivity of each of the four cone
      mechanisms for both spectral and polarization sensitivity. Under spectrally broad
      conditions, UV sensitive (UVS), mid wavelength sensitive (MWS) and long
      wavelength sensitive (LWS) cone mechanisms contributed to polarization
      sensitivity. CAP recordings produced the typical 'W' shaped polarization
      sensitivity curve reflecting two active polarization detectors with peaks at e
      vector orientations of 0 deg, 90 deg and 180 deg, and troughs at 30 deg and 150
      deg. ERG recordings produced a four-peaked polarization sensitivity curve
      reflecting two active polarization detectors and negative feedback activity, with
      peaks at e-vectors 0 deg, 45 deg, 90 deg, 135 deg and 180 deg, and troughs at 30
      deg, 60 deg, 120 deg and 150 deg. Polarization-sensitivity measurements of
      isolated cone mechanisms revealed two orthogonal polarization detector mechanisms
      in Atlantic salmon, identical to that found in rainbow trout and other Pacific
      salmonid fishes. Moreover, under spectrally broad background conditions, CAP and
      ERG polarization sensitivity of Atlantic salmon did not differ significantly from
      that reported in Pacific salmonids.

PMID- 20802122
TI  - Effects of feeding on thermoregulatory behaviours and gut blood flow in white
      sturgeon (Acipenser transmontanus) using biotelemetry in combination with
      standard techniques.
AB  - The effects of thermoregulatory behaviours on gut blood flow in white sturgeon
      Acipenser transmontanus before and after feeding was studied using a blood flow
      biotelemetry system in combination with a temperature preference chamber. This is
      the first study to look at cardiovascular responses to feeding in white sturgeon,
      and also the first time behavioural tests in fish have been combined with
      recordings of cardiac output, heart rate, cardiac stroke volume and gut blood
      flow. The results showed strong correlations between gut blood flow and
      temperature choice after feeding (R(2)=0.88+/-0.03, 6-8 h postprandially and
      R(2)=0.89+/-0.04, 8-10 h postprandially) but not prior to feeding (R(2)=0.11+/
      0.05). Feeding did not affect the actual temperature preference (18.4+/-0.7
      degrees C before feeding, 18.1+/-0.7 degrees C, 6-8 h postprandially and 17.5+/
      0.5 degrees C, 8-10 h postprandially). Fish instrumented with a blood flow
      biotelemetry device, and allowed to move freely in the water, had a significantly
      lower resting heart rate (37.3+/-0.26 beats min(-1)) compared with the control
      group that was traditionally instrumented with transit-time blood flow probes and
      kept in a confined area in accordance with the standard procedure (43.2+/-2.1
      beats min(-1)). This study shows, for the first time in fish, the correlation
      between body temperature and gut blood flow during behavioural thermoregulation.

PMID- 20802123
TI  - Plasticity in extended phenotypes: orb web architectural responses to variations
      in prey parameters.
AB  - A spider orb web is an extended phenotype; it modifies and interacts with the
      environment, influencing spider physiology. Orb webs are plastic, responding to
      variations in prey parameters. Studies attempting to understand how nutrients
      influence spider orb-web plasticity have been hampered by the inability to
      decouple prey nutrients from other, highly correlated, prey factors and the
      intrinsic link between prey protein and prey energy concentration. I analyzed the
      nutrient concentrations of cockroaches, and adult and juvenile crickets to devise
      experiments that controlled prey protein concentration while varying prey size,
      ingested mass, energy concentration and feeding frequency of the orb web spider
      Argiope keyserlingi. I found that A. keyserlingi alters overall architecture
      according to feeding frequency. Decoration length was inversely related to
      ingested prey mass and/or energy density in one experiment but directly related
      to ingested prey mass in another. These contradictory results suggest that
      factors not examined in this study have a confounding influence on decoration
      plasticity. As decorations attract prey as well as predators decreasing
      decoration investment may, in some instances, be attributable to benefits no
      longer outweighing the risks. Web area was altered according to feeding
      frequency, and mesh size altered according to feeding frequency and prey length.
      The number of radii in orb webs was unaffected by prey parameters. A finite
      amount of silk can be invested in the orb web, so spiders trade-off smaller mesh
      size with larger web capture area, explaining why feeding frequency influenced
      both web area and mesh size. Mesh size is additionally responsive to prey size
      via sensory cues, with spiders constructing webs suitable for catching the most
      common or most profitable prey.

PMID- 20802124
TI  - Effects of heterospecific and conspecific vibrational signal overlap and signal
      to-noise ratio on male responsiveness in Nezara viridula (L.).
AB  - Animals often communicate in environments with high levels of biotic noise that
      arises from the signals of other individuals. Although effects of background
      biotic noise on mate recognition and discrimination have been widely studied in
      air-born sound communication, little is known about incidental interference
      between signallers that use substrate-borne vibrational signals. In this study we
      investigated the ability of males of the southern green stink bug Nezara viridula
      (L.) (Heteroptera: Pentatomidae) to recognize conspecific female song in the
      presence of biotic noise originating from conspecific and heterospecific
      vibrational signals. We tested male responsiveness on a bean plant in playback
      experiments. One leaf was vibrated with conspecific female song, while to the
      other one we simultaneously applied either heterospecific female signal or
      various altered conspecific signals with different temporal parameters. We tested
      males in three levels of biotic noise, ranging from +6 dB to -6 dB and we
      compared male responsiveness in each treatment with response obtained in
      unilateral treatment with unaltered conspecific female calling song. Male
      responsiveness was reduced in the presence of heterospecific signals or when
      background noise from conspecific signals obscured the species-specific temporal
      pattern of conspecific female song. By contrast, the presence of two sources of
      conspecific female songs had a positive effect on male responsiveness, for as
      long as the signal repetition rate of perceived song did not differ from the
      species-specific value. In the presence of interfering background signals,
      searching activity was less affected than male signalling. Increased signal-to
      noise ratio restored male responsiveness to the level expressed in unilateral
      stimulation with conspecific female song. The results are discussed with regard
      to male behavioural strategies for vibrational communication in a noisy
      environment.

PMID- 20802125
TI  - An entomopathogenic Caenorhabditis briggsae.
AB  - Caenorhabditis elegans is a premier model organism upon which considerable
      knowledge of basic cell and developmental biology has been built. Yet, as is true
      for many traditional model systems, we have limited knowledge of the ecological
      context in which these systems evolved, severely limiting our understanding of
      gene function. A better grasp of the ecology of model systems would help us
      immensely in understanding the functionality of genes and evolution of genomes in
      an environmental context. Consequently, there are ongoing efforts to uncover
      natural populations of this model system globally. Here, we describe the
      discovery of a Caenorhabditis briggsae strain and its bacterial associate
      (Serratia sp.) that form an entomopathogenic complex in the wild. Laboratory
      experiments confirm that this nematode and its natural bacterial associate can
      penetrate, kill and reproduce in an insect host and that the bacterial associate
      can induce this insect pathogenic life cycle in other Caenorhabditis species,
      including C. elegans. Our findings suggest that this life history may be
      widespread in nature and critical to the understanding of the biology of this
      important model organism. Caenorhabditis-insect interaction could be a key factor
      in our quest for a better grasp of gene functionality in this important model
      species. The discovered association, consequently, would provide an ecological
      framework for functional genomics of Caenorhabditis.

PMID- 20802126
TI  - Call properties and morphology of the sound-producing organ in Ophidion rochei
      (Ophidiidae).
AB  - The anatomical structures of the sound-producing organ in Ophidion rochei males
      present an important panel of highly derived characters: three pairs of
      putatively slow sonic muscles; a neural arch that pivots; a rocker bone at the
      front pole of the swimbladder; a stretchable swimbladder fenestra; a swimbladder
      plate; and an internal cone that terminates in a pair of membranes in the caudal
      swimbladder. Male courtship calls are produced nocturnally and consist of trains
      of 10 to 40 pulses that increase in amplitude and decrease in rate before
      exhibiting alternating periods of ca. 84 and 111 ms. Each pulse includes an
      unusual waveform with two parts. Pulse part 1 is a single cycle followed by a
      longer duration pulse part that exhibits gradual damping. Sounds and morphology
      suggest two hypotheses on the sound-producing mechanism. The 'pulley' hypothesis
      would require an alternate contraction of the ventral and dorsal muscles to form
      the two parts of each pulse. The 'bow' hypothesis involves a release mechanism
      with the sustained contraction of the dorsal muscle during all of the call, and
      the rapid contraction/relaxation of the ventral muscle to form each pulse.

PMID- 20802127
TI  - Swimming behavior and prey retention of the polychaete larvae Polydora ciliata
      (Johnston).
AB  - The behavior of the ubiquitous estuarine planktotrophic spionid polychaete larvae
      Polydora ciliata was studied. We describe ontogenetic changes in morphology,
      swimming speed and feeding rates and have developed a simple swimming model using
      low Reynolds number hydrodynamics. In the model we assumed that the ciliary
      swimming apparatus is primarily composed of the prototroch and secondarily by the
      telotroch. The model predicted swimming speeds and feeding rates that
      corresponded well with the measured speeds and rates. Applying empirical data to
      the model, we were able to explain the profound decrease in specific feeding
      rates and the observed increase in the difference between upward and downward
      swimming speeds with larval size. We estimated a critical larval length above
      which the buoyancy-corrected weight of the larva exceeds the propulsion force
      generated by the ciliary swimming apparatus and thus forces the larva to the
      bottom. This modeled critical larval length corresponded to approximately 1 mm,
      at which, according to the literature, competence for metamorphosis and no more
      length increase is observed. These findings may have general implications for all
      planktivorous polychaete larvae that feed without trailing threads. We observed
      bell shaped particle retention spectra with a minimum prey size of approximately
      4 microm equivalent spherical diameter, and we found that an ontogenetic increase
      in maximum prey size add to a reduction in intra-specific food competition in the
      various larval stages. In a grazing experiment using natural seawater, ciliates
      were cleared approximately 50% more efficiently than similar sized
      dinoflagellates. The prey sizes retainable for P. ciliata larvae covers the
      microplankton fraction and includes non-motile as well as motile prey items,
      which is why the larvae are trophically positioned among the copepods and
      dinoflagellates. Not only do larval morphology and behavior govern larval
      feeding, prey behavior also influences the feeding efficiency of Polydora
      ciliata.

PMID- 20802128
TI  - Folic acid mitigated cardiac dysfunction by normalizing the levels of tissue
      inhibitor of metalloproteinase and homocysteine-metabolizing enzymes
      postmyocardial infarction in mice.
AB  - Myocardial infarction (MI) results in significant metabolic derangement, causing
      accumulation of metabolic by product, such as homocysteine (Hcy). Hcy is a
      nonprotein amino acid generated during nucleic acid methylation and demethylation
      of methionine. Folic acid (FA) decreases Hcy levels by remethylating the Hcy to
      methionine, by 5-methylene tetrahydrofolate reductase (5-MTHFR). Although
      clinical trials were inconclusive regarding the role of Hcy in MI, in animal
      models, the levels of 5-MTHFR were decreased, and FA mitigated the MI injury. We
      hypothesized that FA mitigated MI-induced injury, in part, by mitigating cardiac
      remodeling during chronic heart failure. Thus, MI was induced in 12-wk-old male
      C57BL/J mice by ligating the left anterior descending artery, and FA (0.03 g/l in
      drinking water) was administered for 4 wk after the surgery. Cardiac function was
      assessed by echocardiography and by a Millar pressure-volume catheter. The levels
      of Hcy-metabolizing enzymes, cystathionine beta-synthase (CBS), cystathionine
      gamma-lyase (CSE), and 5-MTHFR, were estimated by Western blot analyses. The
      results suggest that FA administered post-MI significantly improved cardiac
      ejection fraction and induced tissue inhibitor of metalloproteinase, CBS, CSE,
      and 5-MTHFR. We showed that FA supplementation resulted in significant
      improvement of myocardial function after MI. The study eluted the importance of
      homocysteine (Hcy) metabolism and FA supplementation in cardiovascular disease.

PMID- 20802129
TI  - Protease corin expression and activity in failing hearts.
AB  - Atrial and brain natriuretic peptides (ANP and BNP) regulate blood pressure and
      cardiac function. In patients with heart failure (HF), plasma levels of pro-ANP
      and pro-BNP, the precursor forms of ANP and BNP, are highly elevated, but the
      mechanism underlying the apparent deficiency in natriuretic peptide processing is
      unclear. Corin is a cardiac protease that activates natriuretic peptides. In this
      study, we examined corin protein expression and activity in mouse and human
      failing hearts. Tissue samples were obtained from a mouse model of HF induced by
      myotrophin overexpression and from human nonfailing, hypertrophic, and failing
      hearts. Corin protein levels in the membrane fraction and tissue lysate were
      measured by Western blotting and ELISA. Corin catalytic and biological activities
      were measured by fluorescent substrate and pro-ANP processing assays. In mice,
      corin protein levels did not change with age in normal hearts but increased
      significantly in failing hearts. In humans, corin protein levels were similar in
      the atrium from nonfailing and failing hearts but were increased in the ventricle
      in failing hearts compared with those in nonfailing or hypertrophic hearts.
      Unlike the protein level, however, corin activity did not increase in failing
      hearts, as measured by fluorogenic substrate and pro-ANP processing assays. Our
      results indicate that corin activation is a rate-limiting step in failing hearts.
      Insufficient corin activation is expected to prevent natriuretic peptide
      processing and may contribute to body fluid retention and impaired cardiac
      function in patients with HF.

PMID- 20802130
TI  - Transforming growth factor-beta1 regulation of C-type natriuretic peptide
      expression in human vascular smooth muscle cells: dependence on TSC22D1.
AB  - C-type natriuretic peptide (CNP) possesses nitric oxide-like signaling mechanisms
      and actions in the vasculature, including the inhibition of fibrosis and vascular
      remodeling through counterregulation of transforming growth factor-beta (TGF
      beta) signaling. The leucine zipper protein transforming growth factor stimulated
      clone 22 domain 1 (TSC22D1), cloned via its presumed binding to a GC-rich element
      in the CNP promoter, was the first protein to be described as a CNP transcription
      factor, but the lack of supporting evidence since its discovery and its lack of a
      classical DNA-binding site have left in question its role in the regulation of
      CNP by TGF-beta and other factors. To define a specific role for TSC22D1 in CNP
      transcription, we have examined the effects of the profibrotic growth factors TGF
      beta1 and PDGF-BB on CNP mRNA expression in cultured human vascular smooth muscle
      cells (SMC) in which TSC22D1 expression was suppressed with small interfering
      RNA. Results showed that TGF-beta and PDGF-BB significantly increased CNP
      expression in all three SMC types. Twenty-four-hour TGF-beta-induced elevations
      in CNP were strongly correlated with changes in TSC22D1 mRNA levels, and both
      genes exhibited their greatest response to TGF-beta1 in coronary artery SMC.
      Furthermore, siRNA suppression of TSC22D1 expression in coronary artery and
      aortic SMC by ~90% resulted in 45-65% reductions of both PDGF- and TGF-beta
      stimulated CNP expression, respectively. These results support a postulated role
      of TSC22D1 as an enhancer of CNP transcription and suggest that TGF-beta-induced
      upregulation of CNP expression in SMC may be mediated in part by increased
      transcription of TSC22D1.

PMID- 20802131
TI  - Pretreatment with the nitric oxide donor SNAP or nerve transection blocks humoral
      preconditioning by remote limb ischemia or intra-arterial adenosine.
AB  - We have previously shown that remote ischemic preconditioning (rIPC) by transient
      limb ischemia leads to the release of a circulating factor(s) that induces potent
      myocardial protection. Intra-arterial injection of adenosine into a limb also
      leads to cardioprotection, but the mechanism of its signal transduction is poorly
      understood. Eleven groups of rabbits received saline control or rIPC or adenosine
      administration with additional pretreatment with the nitric oxide (NO) synthase
      blocker N(G)-nitro-l-arginine methyl ester, the NO donor S-nitroso-N
      acetylpenicillamine, its non-NO-donating derivative N-acetylpenicillamine, or
      femoral nerve section. Blood was then drawn from each animal, and the dialysate
      of the plasma was used to perfuse a naive heart from an untreated donor. Infarct
      size was measured after 30 min of global ischemia and 120 min reperfusion. When
      compared with that of the control, mean infarct size was significantly smaller in
      groups treated with rIPC alone (P < 0.01) and intra-arterial adenosine (P <
      0.01). Pretreatment with N(G)-nitro-l-arginine methyl ester or N
      acetylpenicillamine did not affect the level of protection induced by rIPC (P =
      not significant, compared with rIPC alone) or intra-arterial adenosine (P = not
      significant, compared with intra-arterial adenosine alone), but prior femoral
      nerve transection or pretreatment with S-nitroso-N-acetylpenicillamine abolished
      the cardioprotective effect of intra-arterial adenosine and rIPC. Intra-arterial
      adenosine, like rIPC, releases a blood-borne cardioprotective factor(s) that is
      dependent on an intact femoral nerve and is inhibited by pretreatment with a NO
      donor. These results may be important when designing or assessing the results of
      clinical trials of adenosine or rIPC cardioprotection, where NO donors are used
      as part of therapy.

PMID- 20802132
TI  - Genetically manipulated progenitor cell sheet with diprotin A improves myocardial
      function and repair of infarcted hearts.
AB  - We postulated that the combination of overexpression of CXCR4 in mesenchymal stem
      cells (MSC) with diprotin A would enhance MSC recruitment and penetration into
      ischemic myocardium, leading to an improvement in heart function after myocardial
      infarction (MI). Male rat MSC were genetically engineered with adenoviral vectors
      coexpressing CXCR4 and enhanced green fluorescent protein (EGFP) (MSC(CXCR4)),
      GFP alone (MSC(Null), control), or siRNA-targeted CXCR4 (MSC(siRNA)). Cell sheets
      were applied over the surface of infarcted left ventricle (LV) in female rats 7
      days after ligation of the left anterior descending coronary artery (LAD)
      pretreated with either vehicle (VEH) or diprotin A (DIP). At 28 days after cell
      sheet implantation, echocardiography was performed. Hearts were harvested for
      histological analysis 7 days after LAD ligation or 28 days after cell sheet
      implantation. DPP-IV and stroma-derived factor-1alpha (SDF-1alpha) in the LV were
      analyzed. Efficacy of engraftment was determined by the presence of Y chromosome
      in nuclei (Y(ch+)). LV blood vessel density and apoptosis were also analyzed.
      Myocardial SDF-1alpha was elevated before placement of the cell sheet in the DIP
      group compared with vehicle group on day 7 after LAD. On day 28 after cell sheet
      transplantation, the number of Y(ch+) was increased in the MSC(CXCR4) + VEH group
      compared with the MSC(Null) + VEH group and further increased in the MSC(CXCR4) +
      DIP treated group. This enhanced response was associated with increased
      angiogenesis in both sides of epicardium and improvement of LV function.
      Combination of gene-manipulated MSC(CXCR4) patch with DIP pretreatment inhibits
      myocardial ischemia-induced apoptosis, promotes tissue angiogenesis, and enhances
      cell engraftment, leading to improved LV mechanical function after MI.

PMID- 20802133
TI  - Limb movement-induced hyperemia has a central hemodynamic component: evidence
      from a neural blockade study.
AB  - The purpose of this investigation was to partially remove feedback from type
      III/IV skeletal muscle afferents and determine how this feedback influences the
      central and peripheral hemodynamic responses to passive leg movement. Heart rate
      (HR), stroke volume (SV), cardiac output (CO), mean arterial pressure, leg
      vascular conductance (LVC), and leg blood flow (LBF) were measured during 2 min
      of passive knee extension in eight young men before and after intrathecal
      fentanyl injection. Passive movement increased HR by 14 beats/min from baseline
      to maximal response during control (CON) (65 +/- 4 to 79 +/- 5 beats/min, P <
      0.05), whereas HR did not significantly increase with the fentanyl block (BLK).
      LBF and LVC increased in both conditions; however, these increases were
      attenuated and delayed during BLK [%change from baseline to maximum, LBF: CON 295
      +/- 109 vs. BLK 210 +/- 86%, (P < 0.05); LVC: CON 322 +/- 40% vs. BLK 231 +/-
      32%, (P < 0.04)]. In CON, HR, SV, CO, and LVC increased contributing to the
      hyperemic response. However, under BLK conditions, statistically insignificant
      increases in HR and SV combined to yield a small, but significant, increase in CO
      and an attenuated hyperemic response. Therefore, partially blocking skeletal
      muscle afferent feedback blunts the central hemodynamic response due to passive
      limb movement, which then results in an attenuated and delayed movement-induced
      hyperemia. In combination, these findings provide evidence that limb movement
      induced hyperemia has a significant central hemodynamic component induced by
      peripheral nerve activation.

PMID- 20802134
TI  - Sigma1-receptor stimulation with fluvoxamine ameliorates transverse aortic
      constriction-induced myocardial hypertrophy and dysfunction in mice.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are known to reduce post
      myocardial infarction-induced morbidity and mortality. However, the molecular
      mechanism underlying SSRI-induced cardioprotection remains unclear. Here, we
      investigated the role of sigma(1)-receptor (sigma(1)R) stimulation with
      fluvoxamine on myocardial hypertrophy and cardiac functional recovery. Male ICR
      mice were subjected to transverse aortic constriction (TAC) in the cardiac aortic
      arch. To confirm the cardioprotective role of fluvoxamine by sigma(1)R
      stimulation, we treated mice with fluvoxamine (0.5 or 1 mg/kg) orally once per
      day for 4 wk after the onset of aortic banding. Interestingly, in untreated mice,
      sigma(1)R expression in the left ventricle (LV) decreased significantly over the
      4 wk as TAC-induced hypertrophy increased. In contrast, fluvoxamine
      administration significantly attenuated TAC-induced myocardial hypertrophy
      concomitant with recovery of sigma(1)R expression in the LV. Fluvoxamine also
      attenuated hypertrophy-induced impaired LV fractional shortening. The fluvoxamine
      cardioprotective effect was nullified by treatment with a sigma(1)R antagonist
      [NE-100 (1 mg/kg)]. Importantly, another SSRI with very low affinity for
      sigma(1)Rs, paroxetine, did not elicit antihypertrophic effects in TAC mice and
      cultured cardiomyocytes. Fluvoxamine treatment significantly restored TAC-induced
      impaired Akt and endothelial nitric oxide synthase (eNOS) phosphorylation in the
      LV. Our findings suggest that fluvoxamine protects against TAC-induced cardiac
      dysfunction via upregulated sigma(1)R expression and stimulation of sigma(1)R
      mediated Akt-eNOS signaling in mice. This is the first report of a potential role
      for sigma(1)R stimulation by fluvoxamine in attenuating cardiac hypertrophy and
      restoring contractility in TAC mice.

PMID- 20802135
TI  - Exaggerated sympathetic and pressor responses to handgrip exercise in older
      hypertensive humans: role of the muscle metaboreflex.
AB  - Recent animal studies have reported that exercise pressor reflex (EPR)-mediated
      increases in blood pressure are exaggerated in hypertensive (HTN) rodents.
      Whether these findings can be extended to human hypertension remains unclear.
      Mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), and
      venous metabolites were measured in normotensive (NTN; n = 23; 60 +/- 1 yr) and
      HTN (n = 15; 63 +/- 1 yr) subjects at baseline, and during static handgrip at 30
      and 40% maximal voluntary contraction (MVC) followed by a period of postexercise
      ischemia (PEI) to isolate the metabolic component of the EPR. Changes in MAP from
      baseline were augmented in HTN subjects during both 30 and 40% MVC handgrip (P <
      0.05 for both), and these group differences were maintained during PEI (30% PEI
      trial: Delta15 +/- 2 NTN vs. Delta19 +/- 2 HTN mmHg; 40% PEI trial: Delta16 +/- 1
      NTN vs. Delta23 +/- 2 HTN mmHg; P < 0.05 for both). Similarly, in HTN subjects,
      MSNA burst frequency was greater during 30 and 40% MVC handgrip (P < 0.05 for
      both), and these differences were maintained during PEI [30% PEI trial: 35 +/- 2
      (NTN) vs. 44 +/- 2 (HTN) bursts/min; 40% PEI trial: 36 +/- 2 (NTN) vs. 48 +/- 2
      (HTN) bursts/min; P < 0.05 for both]. No group differences in metabolites were
      observed. MAP and MSNA responses to a cold pressor test were not different
      between groups, suggesting no group differences in generalized sympathetic
      responsiveness. In summary, compared with NTN subjects, HTN adults exhibit
      exaggerated sympathetic and pressor responses to handgrip exercise that are
      maintained during PEI, indicating that activation of the metabolic component of
      the EPR is augmented in older HTN humans.

PMID- 20802136
TI  - Cre-loxP DNA recombination is possible with only minimal unspecific
      transcriptional changes and without cardiomyopathy in Tg(alphaMHC-MerCreMer)
      mice.
AB  - Cre-loxP technology for conditional gene inactivation is a powerful tool in
      cardiovascular research. Induction of gene inactivation can be carried out by per
      oral or intraperitoneal tamoxifen administration. Unintended transient
      cardiomyopathy following tamoxifen administration for gene inactivation has
      recently been reported. We aimed to develop a protocol for tamoxifen-induced gene
      inactivation with minimal effects on gene transcription and in vivo cardiac
      function, allowing studies of acute loss of the targeted gene. In mRNA
      microarrays, 35% of the 34,760 examined genes were significantly regulated in
      MCM(+/0) compared with wild type. In MCM(+/0), we found a correlation between
      tamoxifen dose and degree of gene regulation. Comparing one and four
      intraperitoneal injections of 40 mg.kg(-1).day(-1) tamoxifen, regulated genes
      were reduced to 1/5 in the single injection group. Pronounced alteration in
      protein abundance and acute cardiomyopathy were observed after the four-injection
      protocols but not the one-injection protocol. For verification of gene
      inactivation following one injection of tamoxifen, this protocol was applied to
      MCM(+/0)/Serca2(fl/fl). Serca2 mRNA levels and protein abundance followed the
      same pattern of decline with one and four tamoxifen injections. The presence of
      the MCM transgene induced major alterations of gene expression while
      administration of tamoxifen induced additional but less gene regulation. Thus
      nonfloxed MCM(+/0) should be considered as controls for mice that carry both a
      floxed gene of interest and the MCM transgene. One single tamoxifen injection
      administered to MCM(+/0)/Serca2(fl/fl) was sufficient for target gene
      inactivation, without acute cardiomyopathy, allowing acute studies subsequent to
      gene inactivation.

PMID- 20802137
TI  - cGMP-dependent protein kinase and the regulation of vascular smooth muscle cell
      gene expression: possible involvement of Elk-1 sumoylation.
AB  - Although the regulation of smooth muscle cell (SMC) gene expression by cGMP
      dependent protein kinase (PKG) is now recognized, the mechanisms underlying these
      effects are not fully understood. In this study, we report that PKG-I stimulates
      myocardin/serum response factor (SRF)-dependent gene expression in vascular SMCs.
      The expression of PKG in PKG-deficient cells enhanced myocardin-induced SM22
      promoter activity in a concentration-dependent fashion. However, neither SRF nor
      myocardin expression was affected. To investigate alternative mechanisms, we
      examined whether PKG affects the phosphorylation of E26-like protein-1 (Elk-1), a
      SRF/myocardin transcription antagonist. The activation of PKG caused an increase
      in a higher molecular mass form of phospho-Elk-1 that was determined to be small
      ubiquitin-related modifier (sumo)ylated Elk-1. PKG increased Elk-1 sumoylation
      twofold compared with the PKG-deficient cells, and Elk-1 sumoylation was reduced
      using dominant-negative sumo-conjugating enzyme, DN-Ubc9, confirming PKG
      dependent sumoylation of phospho-Elk-1 in vascular SMCs. In addition, PKG
      stimulated Elk-1 sumoylation in COS-7 cells overexpressing Elk-1, sumo-1, and PKG
      I. The increased expression of PKG in vascular SMCs inhibited Elk-1 binding to
      SMC-specific promoters, SM22 and smooth muscle myosin heavy chain, as measured by
      EMSA and chromatin immunoprecipitation assay, and PKG suppressed the Elk-1
      inhibition of SM22 reporter gene expression. Taken together, these data suggest
      that PKG-I decreases Elk-1 activity by sumo modification of Elk-1, thereby
      increasing myocardin-SRF activity on SMC-specific gene expression.

PMID- 20802138
TI  - Complex structure of electrophysiological gradients emerging during long-duration
      ventricular fibrillation in the canine heart.
AB  - Long-duration ventricular fibrillation (LDVF) in the globally ischemic heart is a
      common setting of cardiac arrest. Electrical heterogeneities during LDVF may
      affect outcomes of defibrillation and resuscitation. Previous studies in large
      mammalian hearts have investigated the role of Purkinje fibers and
      electrophysiological gradients between the endocardium (Endo) and epicardium
      (Epi). Much less is known about gradients between the right ventricle (RV) and
      left ventricle (LV) and within each chamber during LDVF. We studied the
      transmural distribution of the VF activation rate (VFR) in the RV and LV and at
      the junction of RV, LV, and septum (Sep) during LDVF using plunge needle
      electrodes in opened-chest dogs. We also used optical mapping to analyze the Epi
      distribution of VFR, action potential duration (APD), and diastolic interval (DI)
      during LDVF in the RV and LV of isolated hearts. Transmural VFR gradients
      developed in both the RV and LV, with a faster VFR in Endo. Concurrently, large
      VFR gradients developed in Epi, with the fastest VFR in the RV-Sep junction,
      intermediate in the RV, and slowest in the LV. Optical mapping revealed a
      progressively increasing VFR dispersion within both the LV and RV, with a mosaic
      presence of fully inexcitable areas after 4-8 min of LDVF. The transmural,
      interchamber, and intrachamber VFR heterogeneities were of similar magnitude. In
      both chambers, the inverse of VFR was highly correlated with DI, but not APD, at
      all time points of LDVF. We conclude that the complex VFR gradients during LDVF
      in the canine heart cannot be explained solely by the distribution of Purkinje
      fibers and are related to regional differences in the electrical depression
      secondary to LDVF.

PMID- 20802139
TI  - Gene silencing of myofibrillogenesis regulator-1 by adenovirus-delivered small
      interfering RNA suppresses cardiac hypertrophy induced by angiotensin II in mice.
AB  - Our previous studies proved that myofibrillogenesis regulator (MR)-1 has a close
      relationship with cardiac hypertrophy induced by ANG II. In the present study, we
      developed a recombinant adenoviral vector (AdSiR-MR-1) driving small interfering
      (si)RNA against MR-1 to evaluate its effect on cardiac hypertrophy in vivo.
      Cardiac hypertrophy was induced by chronic ANG II infusion in mice; AdSiR-MR-1
      was administered via the jugular vein through one bolus injection. Thirteen days
      after the injection, viral DNA was still detectable in the heart, validating the
      efficiency of gene transfer. Expression levels of MR-1 mRNA and protein were
      increased by 2.5-fold in the heart after ANG II infusion; AdSiR-control, which
      contained a scrambled siRNA sequence, had no effect on them. AdSiR-MR-1 treatment
      abolished the upregulation of MR-1 induced by ANG II. The silencing effect of
      AdSiR-MR-1 was observed in many other tissues, such as the liver, lung, and
      kidney, except skeletal muscle. ANG II-induced cardiac hypertrophy was suppressed
      in mice treated with AdSiR-MR-1, as determined by echocardiography. Morphological
      and immnohistochemical examinations revealed that interstitial cardiac fibrosis
      as well as infiltrating inflammatory cells were increased after ANG II infusion;
      AdSiR-MR-1 greatly ameliorated these disorders. In ANG II-infused mice, MR-1
      silencing also blocked the upregulation of other genes related to cardiac
      hypertrophy or metabolism of the extracellular matrix. In summary, our results
      demonstrate the feasibility of MR-1 silencing in vivo and suggest that MR-1 could
      be a potential new target to treat cardiac hypertrophy induced by ANG II.

PMID- 20802140
TI  - Loss of connexin40 is associated with decreased endothelium-dependent relaxations
      and eNOS levels in the mouse aorta.
AB  - Upon agonist stimulation, endothelial cells trigger smooth muscle relaxation
      through the release of relaxing factors such as nitric oxide (NO). Endothelial
      cells of mouse aorta are interconnected by gap junctions made of connexin40
      (Cx40) and connexin37 (Cx37), allowing the exchange of signaling molecules to
      coordinate their activity. Wild-type (Cx40(+/+)) and hypertensive Cx40-deficient
      mice (Cx40(-/-)), which also exhibit a marked decrease of Cx37 in the
      endothelium, were used to investigate the link between the expression of
      endothelial connexins (Cx40 and Cx37) and endothelial nitric oxide synthase
      (eNOS) expression and function in the mouse aorta. With the use of isometric
      tension measurements in aortic rings precontracted with U-46619, a stable
      thromboxane A(2) mimetic, we first demonstrate that ACh- and ATP-induced
      endothelium-dependent relaxations solely depend on NO release in both Cx40(+/+)
      and Cx40(-/-) mice, but are markedly weaker in Cx40(-/-) mice. Consistently, both
      basal and ACh- or ATP-induced NO production were decreased in the aorta of Cx40(
      /-) mice. Altered relaxations and NO release from aorta of Cx40(-/-) mice were
      associated with lower expression levels of eNOS in the aortic endothelium of
      Cx40(-/-) mice. Using immunoprecipitation and in situ ligation assay, we further
      demonstrate that eNOS, Cx40, and Cx37 tightly interact with each other at
      intercellular junctions in the aortic endothelium of Cx40(+/+) mice, suggesting
      that the absence of Cx40 in association with altered Cx37 levels in endothelial
      cells from Cx40(-/-) mice participate to the decreased levels of eNOS.
      Altogether, our data suggest that the endothelial connexins may participate in
      the control of eNOS expression levels and function.

PMID- 20802141
TI  - Breed difference and regulation of the porcine Sirtuin 1 by insulin.
AB  - Sirtuin 1 (Sirt1) plays an important role in fat metabolism. In the current
      study, we examined the breed differences in Sirt1 between Jinhua pigs (a fatty
      breed of China) and Landrace pigs (a leaner breed). In addition, the effect of
      insulin on the gene expression of Sirt1 and the major lipase, adipose
      triglyceride lipase (ATGL), and hormone-sensitive lipase (HSL) in fat metabolism
      was also studied in vitro. Compared with the Landrace pigs, the BW of Jinhua pigs
      was less (P < 0.01), whereas the body fat content were greater (P < 0.01). The
      protein content and the mRNA abundance of Sirt1 in Jinhua pigs were less (P <
      0.01) in subcutaneous adipose tissues compared with the Landrace pigs. Likewise,
      the mRNA abundance of ATGL and HSL were also less (P < 0.01) in Jinhua pigs. In
      vitro, treatment with a different dose of insulin (10, 50 and 100 nM) decreased
      (P < 0.01) glycerol release and the mRNA abundance of Sirt1, ATGL, and HSL in
      porcine adipocytes. Likewise, treatment with 50 nM insulin for 24 and 48 h also
      decreased (P < 0.05) glycerol release and the expression of Sirt1, ATGL, and HSL
      in porcine adipocytes. Furthermore, insulin and Sirt1-specific small interfering
      RNA treatment decreased (P < 0.01) the expression of Sirt1, ATGL, and HSL
      compared with the control or insulin treatment. These results indicate that
      insulin may regulate transcription of Sirt1, ATGL, and HSL in porcine adipocytes
      and provide information for manipulating these gene expressions in regulating fat
      metabolism in pigs.

PMID- 20802142
TI  - Phenotypic differences in matrix metalloproteinase 2 activity between fibroblasts
      from 3 bovine muscles.
AB  - Different muscles in a beef carcass are known to respond differently to the same
      stimulus or animal growth pattern or both. This may complicate the search by the
      meat industry for production methods to render meat tender. One of the major
      differences between muscles in the same carcass is in the expression of
      intramuscular connective tissue. Current study investigates the existence of a
      phenotypic difference among fibroblasts from 3 bovine skeletal muscles as
      exemplified by the expression of matrix metalloproteinases (MMP) the main enzymes
      responsible for connective tissue turnover. The sensitivity of phenotypic
      differences to cell culture conditions (passage number, presence of growth
      factors from fetal serum) was also examined. Fibroblasts, the main cells
      responsible for the production and turnover of collagen were isolated from LM,
      semitendinosus (STN), and sternomandibularis (SMD) muscles from a bull calf and
      grown in DMEM, 10% fetal bovine serum, and 5% CO(2). Cell doubling times,
      survival time, resting expression, and activity of MMP and the effect of serum
      withdrawal in the culture media on MMP expression and activity were determined
      for each cell line during 15 passages. Fibroblasts isolated from the 3 muscles
      had different growth potentials. The shortest (P < 0.0001) cell doubling times
      for almost every passage were found in cells from STN muscle. Cells from the LM
      had a shorter (P < 0.0001) survival time in comparison with STN and SMD. Cells
      derived from the STN had greater values (P > 0.05) of MMP-2 activity in
      comparison with LM and SMD cells until passage 4. At passage 15, no activity was
      detected for any cell line. Serum withdrawal generally reduced MMP-2 activation
      but did not eliminate differences in activity between fibroblasts from the 3
      muscles. These results suggest that fibroblasts from different locations are
      phenotypically different and may respond differently to the same growth or
      nutritional stimulus in vitro. This may be related to in vivo differences in
      accumulation, maturity, and turnover of collagen, and ultimately meat tenderness.
      These findings may be important for selecting a management strategy for improving
      meat tenderness by manipulation of animal growth; a strategy applied to the whole
      animal may work for some muscles but not for others.

PMID- 20802143
TI  - Effects of different moving devices at loading on stress response and meat
      quality in pigs.
AB  - Although there is increasing evidence regarding the negative welfare and meat
      quality implications of electric prod use for slaughter-weight pigs, this
      handling tool continues to be used. Therefore, the behavioral and physiological
      response and carcass and meat quality of 360 pigs being loaded onto a truck for
      transportation to slaughter according to 3 handling procedures were studied. The
      3 handling procedures were 1) moving with an electric prod and board from the
      finishing pen to the truck (EP); 2) moving with a board and a paddle from the
      finishing pen to the truck (PAD); 3) moving with a board and a paddle from the
      finishing pen and using a compressed air prod in the ramp before going into the
      truck (CAP). A subpopulation of 144 pigs (48 pigs/treatment) was equipped with
      heart rate monitors. Blood samples were collected from the same animals at
      exsanguination for the analysis of creatine phosphokinase and lactate. Data were
      analyzed using an ANOVA for factorial design, with the animal as the experimental
      unit. Behavior was analyzed with MIXED model procedure with treatment as a fixed
      effect. During loading, EP pigs slipped and fell (P < 0.001) and overlapped (P =
      0.03) more often, but stopped (P < 0.001) and attempted turns (P = 0.01) less
      often than CAP or PAD. With CAP, pigs made more 180 degrees  turns (P = 0.01)
      than with PAD or EP. Loading with EP led to more and longer vocalizations (P =
      0.02 and P = 0.001, respectively) than loading with CAP or PAD. Loading took
      longest with CAP and was quickest with EP (P = 0.01). Pigs handled with EP had a
      greater heart rate than those moved with PAD and CAP at loading (P < 0.001), wait
      at loading (P < 0.001), at unloading (P = 0.05), and in lairage (P = 0.02). Pigs
      loaded with EP had greater (P = 0.05) lactate concentrations in blood at
      exsanguination compared with pigs handled with CAP, with pigs loaded with PAD
      being intermediate. Furthermore, ultimate pH values in the semimembranosus and
      adductor muscles of EP pigs were greater (P = 0.002 and P = 0.004, respectively)
      compared with those from PAD and CAP pigs. Greater (P = 0.04) incidence of blood
      splashed hams was found in EP pigs compared with PAD and CAP pigs. Therefore,
      considering animal welfare, carcass bruising, and blood splashes standpoints, EP
      should be replaced with PAD or CAP. However, additional research is necessary to
      identify methods that improve the loading efficiencies of PAD and CAP without
      adversely affecting animal welfare parameters.

PMID- 20802144
TI  - Disease-related malnutrition and enteral nutrition therapy: a significant problem
      with a cost-effective solution.

PMID- 20802145
TI  - Viral inhibitory peptide of TLR4, a peptide derived from vaccinia protein A46,
      specifically inhibits TLR4 by directly targeting MyD88 adaptor-like and TRIF
      related adaptor molecule.
AB  - TLRs are critical pattern recognition receptors that recognize bacterial and
      viral pathogen-associated molecular patterns leading to innate and adaptive
      immune responses. TLRs signal via homotypic interactions between their
      cytoplasmic Toll/IL-1R (TIR) domains and TIR domain-containing adaptor proteins.
      Over the course of evolution, viruses have developed various immune evasion
      strategies, one of which involves inhibiting TLR signaling pathways to avoid
      immune detection. Thus, vaccinia virus encodes the A46 protein, which binds to
      multiple TIR-domain containing proteins, ultimately preventing TLRs from
      signaling. We have identified an 11-aa-long peptide from A46 (termed viral
      inhibitor peptide of TLR4, or VIPER), which, when fused to a cell-penetrating
      delivery sequence, potently inhibits TLR4-mediated responses. VIPER was TLR4
      specific, being inert toward other TLR pathways, and was active in murine and
      human cells and in vivo, where it inhibited LPS-induced IL-12p40 secretion. VIPER
      also prevented TLR4-mediated MAPK and transcription factor activation, suggesting
      it acted close to the TLR4 complex. Indeed, VIPER directly interacted with the
      TLR4 adaptor proteins MyD88 adaptor-like (Mal) and TRIF-related adaptor molecule
      (TRAM). Viral proteins target host proteins using evolutionary optimized binding
      surfaces. Thus, VIPER possibly represents a surface domain of A46 that
      specifically inhibits TLR4 by masking critical binding sites on Mal and TRAM.
      Apart from its potential therapeutic and experimental use in suppressing TLR4
      function, identification of VIPER's specific binding sites on TRAM and Mal may
      reveal novel therapeutic target sites. Overall, we demonstrate for the first time
      disruption of a specific TLR signaling pathway by a short virally derived
      peptide.

PMID- 20802146
TI  - Inflammasome-dependent release of the alarmin HMGB1 in endotoxemia.
AB  - Endotoxin administration recapitulates many of the host responses to sepsis.
      Inhibitors of the cysteine protease caspase 1 have long been sought as a
      therapeutic because mice lacking caspase 1 are resistant to LPS-induced endotoxic
      shock. According to current thinking, caspase 1-mediated shock requires the
      proinflammatory caspase 1 substrates IL-1beta and IL-18. We show, however, that
      mice lacking both IL-1beta and IL-18 are normally susceptible to LPS-induced
      splenocyte apoptosis and endotoxic shock. This finding indicates the existence of
      another caspase 1-dependent mediator of endotoxemia. Reduced serum high mobility
      group box 1 (HMGB1) levels in caspase 1-deficient mice correlated with their
      resistance to LPS. A critical role for HMGB1 in endotoxemia was confirmed when
      mice deficient for IL-1beta and IL-18 were protected from a lethal dose of LPS by
      pretreatment with HMGB1-neutralizing Abs. We found that HMGB1 secretion from LPS
      primed macrophages required the inflammasome components apoptotic speck protein
      containing a caspase activation and recruitment domain (ASC), caspase 1 and
      Nalp3, whereas HMGB1 secretion from macrophages infected in vitro with Salmonella
      typhimurium was dependent on caspase 1 and Ipaf. Thus, HMGB1 secretion, which is
      critical for endotoxemia, occurs downstream of inflammasome assembly and caspase
      1 activation.

PMID- 20802147
TI  - Suppression of Th2-driven airway inflammation by allergen immunotherapy is
      independent of B cell and Ig responses in mice.
AB  - Allergen-specific immunotherapy (IT) uniquely renders long-term relief from
      allergic symptoms and is associated with elevated serum levels of allergen
      specific IgG and IgA. The allergen-specific IgG response induced by IT treatment
      was shown to be critical for suppression of the immediate phase of the allergic
      response in mice, and this suppression was partially dependent on signaling
      through FcgammaRIIB. To investigate the relevance of the allergen-specific IgG
      responses for suppression of the Th2-driven late-phase allergic response, we
      performed IT in a mouse model of allergic asthma in the absence of FcgammaRIIB or
      FcgammaRI/FcgammaRIII signaling. We found that suppression of Th2 cell activity,
      allergic inflammation, and allergen-specific IgE responses is independent of
      FcgammaRIIB and FcgammaRI/FcgammaRIII signaling. Moreover, we show that the IT
      induced allergen-specific systemic IgG or IgA responses and B cell function are
      dispensable for suppression of the late-phase allergic response by IT treatment.
      Finally, we found that the secretory mucosal IgA response also is not required
      for suppression of the Th2-driven allergic inflammation by IT. These data are in
      contrast to the suppression of the immediate phase of the allergic response,
      which is critically dependent on the induced allergen-specific serum IgG
      response. Hence, IT-induced suppression of the immediate and late phases of the
      allergic response is governed by divergent and independent mechanisms. Our data
      show that the IT-induced suppression of the Th2 cell-dependent late-phase
      allergic response is independent of the allergen-specific IgG and IgA responses
      that are associated with IT treatment.

PMID- 20802148
TI  - Th17 cells contribute to viral replication in coxsackievirus B3-induced acute
      viral myocarditis.
AB  - Acute viral myocarditis (AVMC) is characterized by virus-triggered myocardial
      inflammation, and Coxsackievirus B3 (CVB3) is the primary pathogen. We previously
      proved that Th17 cells, besides having proinflammatory effects, were involved in
      AVMC by enhancing humoral response. However, the relationship between Th17 cells
      and CVB3 replication remains unknown. In this experiment, we infected BALB/c mice
      with CVB3 for establishing AVMC models and then found that, with the increase of
      viral replication, the expressions of splenic Th17 cells, serum IL-17, and
      cardiac IL-17 mRNA were elevated significantly, accompanied by the progressive
      cardiac injuries of AVMC. Furthermore, on day 5, the peak time for viral
      replication, correlation was positive between cardiac IL-17 mRNA and CVB3 RNA
      (correlation index = 0.835; p < 0.01). Although the expressions of Th1 and CD8(+)
      T cells, which could secrete the antiviral cytokine IFN-gamma and damage the
      heart, were also elevated, along with Th17 cells, in AVMC, the neutralization of
      IL-17 further upregulated the percentages of splenic Th1 and CD8(+) T cells and
      the levels of cardiac IFN-gamma mRNA. The cardiac pathological changes were
      obviously improved after neutralization, with reduced viral replication followed
      by decreases in the cardiac inflammatory cytokines IL-17, TNF-alpha, and IL
      1beta. These data suggest that Th17 cells contribute to CVB3 replication in AVMC,
      and that IL-17 might be an important target for regulating the balance of
      antiviral immunities.

PMID- 20802149
TI  - Cutting edge: Hematopoietic-derived APCs select regulatory T cells in thymus.
AB  - Recognition of self-peptide-MHC complexes by high-affinity TCRs and CD28
      signaling are critical for the development of forkhead-winged helix box
      transcription factor 3(+) regulatory T cells (Tregs) in thymus. However, the type
      of APCs that are responsible for selecting Tregs has remained unclear. To dissect
      the role of hematopoietic-derived APCs (HCs) and thymic epithelial cells (TECs)
      in Treg selection, we constructed bone marrow chimeras with disrupted CD28/B7
      signaling in the HC or TEC compartment and analyzed the generation of Tregs in
      the thymus. We found that both HCs and TECs were independently able to fully
      reconstitute the Treg population in the thymus of bone marrow chimeras. In
      addition, Treg selection requires the TCR signal and CD28 costimulation presented
      in cis on the same APC type in vivo. This study demonstrates a new role, to our
      knowledge, for HCs in the development of Tregs in thymus.

PMID- 20802150
TI  - Humans differ from other hominids in lacking an activating NK cell receptor that
      recognizes the C1 epitope of MHC class I.
AB  - Modulation of human NK cell function by killer cell Ig-like receptors (KIR) and
      MHC class I is dominated by the bipartite interactions of inhibitory lineage III
      KIR with the C1 and C2 epitopes of HLA-C. In comparison, the ligand specificities
      and functional contributions of the activating lineage III KIR remain poorly
      understood. Using a robust, sensitive assay of KIR binding and a representative
      panel of 95 HLA class I targets, we show that KIR2DS1 binds C2 with ~50% the
      avidity of KIR2DL1, whereas KIR2DS2, KIR2DS3, and KIR2DS5 have no detectable
      avidity for C1, C2, or any other HLA class I epitope. In contrast, the chimpanzee
      has activating C1- and C2-specific lineage III KIR with strong avidity,
      comparable to those of their paired inhibitory receptors. One variant of
      chimpanzee Pt-KIR3DS2, the activating C2-specific receptor, has the same avidity
      for C2 as does inhibitory Pt-KIR3DL4, and a second variant has ~73% the avidity.
      Chimpanzee Pt-KIR3DS6, the activating C1-specific receptor, has avidity for C1
      that is ~70% that of inhibitory Pt-KIR2DL6. In both humans and chimpanzees we
      observe an evolutionary trend toward reducing the avidity of the activating C1-
      and C2-specific receptors through selective acquisition of attenuating
      substitutions. However, the extent of attenuation has been extreme in humans, as
      exemplified by KIR2DS2, an activating C1-specific receptor that has lost all
      detectable avidity for HLA class I. Supporting such elimination of activating C1
      specific receptors as a uniquely human phenomenon is the presence of a high
      avidity activating C1-specific receptor (Gg-KIR2DSa) in gorilla.

PMID- 20802151
TI  - Secreted immunodominant Mycobacterium tuberculosis antigens are processed by the
      cytosolic pathway.
AB  - Exposure to Mycobacterium tuberculosis can result in lifelong but asymptomatic
      infection in most individuals. Although CD8(+) T cells are elicited at high
      frequencies over the course of infection in both humans and mice, how phagosomal
      M. tuberculosis Ags are processed and presented by MHC class I molecules is
      poorly understood. Broadly, both cytosolic and noncytosolic pathways have been
      described. We have previously characterized the presentation of three HLA-I
      epitopes from M. tuberculosis and shown that these Ags are processed in the
      cytosol, whereas others have demonstrated noncytosolic presentation of the 19-kDa
      lipoprotein as well as apoptotic bodies from M. tuberculosis-infected cells. In
      this paper, we now characterize the processing pathway in an additional six M.
      tuberculosis epitopes from four proteins in human dendritic cells. Addition of
      the endoplasmic reticulum-Golgi trafficking inhibitor, brefeldin A, resulted in
      complete abrogation of Ag processing consistent with cytosolic presentation.
      However, although addition of the proteasome inhibitor epoxomicin blocked the
      presentation of two epitopes, presentation of four epitopes was enhanced. To
      further examine the requirement for proteasomal processing of an epoxomicin
      enhanced epitope, an in vitro proteasome digestion assay was established. We find
      that the proteasome does indeed generate the epitope and that epitope generation
      is enhanced in the presence of epoxomicin. To further confirm that both the
      epoxomicin-inhibited and epoxomicin-enhanced epitopes are processed
      cytosolically, we demonstrate that TAP transport and new protein synthesis are
      required for presentation. Taken together, these data demonstrate that
      immunodominant M. tuberculosis CD8(+) Ags are processed and presented using a
      cytosolic pathway.

PMID- 20802152
TI  - Cutting edge: Expression of the transcription factor E74-like factor 4 is
      regulated by the mammalian target of rapamycin pathway in CD8+ T cells.
AB  - T cell receptor activation inhibits expression of the E74-like factor (ELF) 4 and
      Kruppel-like factor 4 genes to release naive CD8(+) T cells from their quiescent
      state. In this study, we show that ELF4 controls the ERK-mediated proliferative
      response by maintaining normal levels of dual-specificity phosphatases 1 and 5 in
      CD8(+) T cells. In activated CD8(+) T cells, the mammalian target of rapamycin
      pathway inhibits ELF4 and Kruppel-like factor 4 expression downstream of ERK and
      PI3K signaling. Our findings demonstrate that rapamycin could be used to modulate
      expression of this transcriptional network involved in cell-cycle regulation.

PMID- 20802153
TI  - Immature NK cells, capable of producing IL-22, are present in human uterine
      mucosa.
AB  - NK cells are the dominant population of immune cells in the endometrium in the
      secretory phase of the menstrual cycle and in the decidua in early pregnancy. The
      possibility that this is a site of NK cell development is of particular interest
      because of the cyclical death and regeneration of the NK population during the
      menstrual cycle. To investigate this, we searched for NK developmental stages 1
      4, based on expression of CD34, CD117, and CD94. In this study, we report that a
      heterogeneous population of stage 3 NK precursor (CD34(-)CD117(+)CD94(-)) and
      mature stage 4 NK (CD34(-)CD117(-/+)CD94(+)) cells, but not multipotent stages 1
      and 2 (CD34(+)), are present in the uterine mucosa. Cells within the uterine
      stage 3 population are able to give rise to mature stage 4-like cells in vitro
      but also produce IL-22 and express RORC and LTA. We also found stage 3 cells with
      NK progenitor potential in peripheral blood. We propose that stage 3 cells are
      recruited from the blood to the uterus and mature in the uterine microenvironment
      to become distinctive uterine NK cells. IL-22 producers in this population might
      have a physiological role in this specialist mucosa dedicated to reproduction.

PMID- 20802154
TI  - Immunomodulation of delayed-type hypersensitivity responses by mesenchymal stem
      cells is associated with bystander T cell apoptosis in the draining lymph node.
AB  - Disease amelioration by mesenchymal stem cells (MSCs) has been shown to be
      closely related to their immunomodulatory functions on the host immune system in
      many disease models. However, the underlying mechanisms of how these cells affect
      the immune cells in vivo are not fully understood. In this study, we report
      findings that a small but significant number of MSCs accumulate in the secondary
      lymphoid organs and attenuate delayed-type hypersensitivity (DTH) response by
      inducing apoptotic cell death of surrounding immune cells in the draining lymph
      node (LN). In the migration study, i.v. infused GFP-MSCs preferentially
      accumulated at the boundary between the paracortical area and the germinal center
      in the LNs, in close proximity to various types of immune cells including T, B,
      and dendritic cells in a dose-dependent manner. As a result, accumulated MSCs
      markedly attenuated DTH response in proportion to the number of MSCs infused.
      During the DTH response, the infiltration of T cells in the challenged site was
      significantly decreased, whereas a number of apoptotic T cells were remarkably
      increased in the draining LN. Apoptosis was significantly induced in activated T
      cells (CD3(+) and BrdU(+)), but not in the resting T cells (CD3(+) and BrdU(-)).
      NO was associated with these apoptotic events. Taken together, we conclude that
      significant numbers of i.v. infused MSCs preferentially localize in the draining
      LN, where they induce apoptosis of the activated T cells by producing NO and thus
      attenuate the DTH response.

PMID- 20802155
TI  - Sox17 modulates Wnt3A/beta-catenin-mediated transcriptional activation of the Lef
      1 promoter.
AB  - Wnt/beta-catenin-dependent activation of lymphoid enhancer factor 1 (Lef-1) plays
      an important role in numerous developmental processes. In this context,
      transcription of the Lef-1 gene is increased by Wnt-mediated TCF4/beta-catenin
      activation on the Lef-1 promoter through mechanisms that remain poorly defined.
      In mouse airway submucosal gland progenitor cells, Wnt3A transiently induces Lef
      1 gene expression, and this process is required for epithelial cell proliferation
      and glandular morphogenesis. In the present study, we sought to identify
      additional candidate transcriptional regulators of the Lef-1 gene during
      glandular morphogenesis. To this end, we found that Sox17 expression is
      dramatically downregulated in early glandular progenitor cells that induce Lef-1
      expression. Wnt stimulation of undifferentiated primary airway epithelial cells
      induced similar changes in Sox17 and Lef-1 expression. Reporter assays revealed
      that ectopic expression of Sox17 suppresses Wnt3A/beta-catenin activation of the
      Lef-1 promoter in cell lines. EMSA and ChIP analyses defined several Sox17- and
      TCF4-binding sites that collaborate in transcriptional control of the Lef-1
      promoter. More specifically, Sox17 bound to four sites in the Lef-1 promoter,
      either directly or indirectly through TCF complexes. The DNA- or beta-catenin
      binding domains of Sox17 controlled context-specific binding of Sox17/TCF
      complexes on the Lef-1 promoter. Combinatorial site-directed mutagenesis of Sox17
      or TCF-binding sites in the Lef-1 promoter demonstrated that these sites control
      Wnt/beta-catenin-mediated induction and/or repression. These findings demonstrate
      for the first time that Sox17 can directly regulate Wnt/beta-catenin-dependent
      transcription of the Lef-1 promoter and reveal new context-dependent binding
      sites in the Lef-1 promoter that facilitate protein-protein interactions between
      Sox17 and TCF4.

PMID- 20802157
TI  - Shedding light on photoperiodism.

PMID- 20802156
TI  - RNA helicase A is a DNA-binding partner for EGFR-mediated transcriptional
      activation in the nucleus.
AB  - EGF induces the translocation of EGF receptor (EGFR) from the cell surface to the
      nucleus where EGFR activates gene transcription through its binding to an AT-rich
      sequence (ATRS) of the target gene promoter. However, how EGFR, without a DNA
      binding domain, can bind to the gene promoter is unclear. In the present study,
      we show that RNA helicase A (RHA) is an important mediator for EGFR-induced gene
      transactivation. EGF stimulates the interaction of EGFR with RHA in the nucleus
      of cancer cells. The EGFR/RHA complex then associates with the target gene
      promoter through binding of RHA to the ATRS of the target gene promoter to
      activate its transcription. Knockdown of RHA expression in cancer cells abrogates
      the binding of EGFR to the target gene promoter, thereby reducing EGF/EGFR
      induced gene expression. In addition, interruption of EGFR-RHA interaction
      decreases the EGFR-induced promoter activity. Consistently, we observed a
      positive correlation of the nuclear expression of EGFR, RHA, and cyclin D1 in
      human breast cancer samples. These results indicate that RHA is a DNA-binding
      partner for EGFR-mediated transcriptional activation in the nucleus.

PMID- 20802158
TI  - Sexuality among middle-aged and older adults with diagnosed and undiagnosed
      diabetes: a national, population-based study.
AB  - OBJECTIVE: To describe sexual activity, behavior, and problems among middle-age
      and older adults by diabetes status. RESEARCH DESIGN AND METHODS: This was a
      substudy of 1,993 community-residing adults, aged 57-85 years, from a cross
      sectional, nationally representative sample (N = 3,005). In-home interviews,
      observed medications, and A1C were used to stratify by diagnosed diabetes,
      undiagnosed diabetes, or no diabetes. Logistic regression was used to model
      associations between diabetes conditions and sexual characteristics, separately
      by gender. RESULTS: The survey response rate was 75.5%. More than 60% of
      partnered individuals with diagnosed diabetes were sexually active. Women with
      diagnosed diabetes were less likely than men with diagnosed diabetes (adjusted
      odds ratio 0.28 [95% CI 0.16-0.49]) and other women (0.63 [0.45-0.87]) to be
      sexually active. Partnered sexual behaviors did not differ by gender or diabetes
      status. The prevalence of orgasm problems was similarly elevated among men with
      diagnosed and undiagnosed diabetes compared with that for other men, but erectile
      difficulties were elevated only among men with diagnosed diabetes (2.51 [1.53 to
      4.14]). Women with undiagnosed diabetes were less likely to have discussed sex
      with a physician (11%) than women with diagnosed diabetes (19%) and men with
      undiagnosed (28%) or diagnosed (47%) diabetes. CONCLUSIONS: Many middle-age and
      older adults with diabetes are sexually active and engage in sexual behaviors
      similarly to individuals without diabetes. Women with diabetes were more likely
      than men to cease all sexual activity. Older women with diabetes are as likely to
      have sexual problems but are significantly less likely than men to discuss them.

PMID- 20802160
TI  - Genetic analysis of abdominal fat distribution in SM/J and A/J mice.
AB  - Each abdominal fat depot, such as mesenteric or epididymal, differently
      contributes to the development of insulin resistance. The aim of this study was
      to identify the genetic regions that contribute to fat accumulation in
      epididymal/mesenteric fat and to examine whether or not the genetic regions that
      affect glucose metabolism and body fat distribution are coincident. We previously
      mapped a major quantitative trait locus (QTL) (T2dm2sa) for impaired glucose
      tolerance on chromosome 2 and revealed that SM.A-T2dm2sa congenic mice showed not
      only glucose tolerance but also fat accumulation. In the present study, to
      identify the loci/genes that control the accumulation of abdominal fat, we
      performed QTL analyses of epididymal/mesenteric fat weight by using (A/J x SM.A
      T2dm2sa)F2 mice in which the effect of T2dm2sa was excluded. As a result, two
      highly significant QTLs for mesenteric fat, as well as three significant QTLs for
      epididymal/mesenteric fat, were mapped on the different chromosomal regions. This
      suggests that the fat accumulations in individual fat depots are controlled by
      distinct genomic regions. Our comparison of these QTLs for abdominal fat
      distribution with those for glucose metabolism revealed that the major genetic
      factors affecting body fat distribution do not coincide with genetic factors
      affecting glucose metabolism in (A/J x SM.A-T2dm2sa)F2.

PMID- 20802159
TI  - CGI-58 knockdown in mice causes hepatic steatosis but prevents diet-induced
      obesity and glucose intolerance.
AB  - Mutations of Comparative Gene Identification-58 (CGI-58) in humans cause
      triglyceride (TG) accumulation in multiple tissues. Mice genetically lacking CGI
      58 die shortly after birth due to a skin barrier defect. To study the role of CGI
      58 in integrated lipid and energy metabolism, we utilized antisense
      oligonucleotides (ASOs) to inhibit CGI-58 expression in adult mice. Treatment
      with two distinct CGI-58-targeting ASOs resulted in ~80-95% knockdown of CGI-58
      protein expression in both liver and white adipose tissue. In chow-fed mice, ASO
      mediated depletion of CGI-58 did not alter weight gain, plasma TG, or plasma
      glucose, yet raised hepatic TG levels ~4-fold. When challenged with a high-fat
      diet (HFD), CGI-58 ASO-treated mice were protected against diet-induced obesity,
      but their hepatic contents of TG, diacylglycerols, and ceramides were all
      elevated, and intriguingly, their hepatic phosphatidylglycerol content was
      increased by 10-fold. These hepatic lipid alterations were associated with
      significant decreases in hepatic TG hydrolase activity, hepatic lipoprotein-TG
      secretion, and plasma concentrations of ketones, nonesterified fatty acids, and
      insulin. Additionally, HFD-fed CGI-58 ASO-treated mice were more glucose tolerant
      and insulin sensitive. Collectively, this work demonstrates that CGI-58 plays a
      critical role in limiting hepatic steatosis and maintaining hepatic
      glycerophospholipid homeostasis and has unmasked an unexpected role for CGI-58 in
      promoting HFD-induced obesity and insulin resistance.

PMID- 20802161
TI  - Interactions between the APOA5 -1131T>C and the FEN1 10154G>T polymorphisms on
      omega6 polyunsaturated fatty acids in serum phospholipids and coronary artery
      disease.
AB  - We determined the contribution of the combination of FEN1 10154G>T with the most
      significant association in the analysis of plasma arachidonic acid (AA,
      20:4omega6) and the APOA5-1131T>C on phospholipid omega6PUFA and coronary artery
      disease (CAD). Patients with CAD (n = 807, 27-81 years of age) and healthy
      controls (n = 1123) were genotyped for FEN1 10154G>T and APOA5-1131T>C. We found
      a significant interaction between these two genes for CAD risk (P = 0.007)
      adjusted for confounding factors. APOA5-1131C allele carriers had a higher CAD
      risk [odds ratio (OR):1.484, 95% confidence interval (CI):1.31-1.96; P = 0.005]
      compared with APOA5-1131TT individuals in the FEN1 10154GG genotype group but not
      in the FEN1 10154T allele group (OR:1.096, 95%CI:0.84-1.43; P = 0.504).
      Significant interactions between these two genes were also observed for the AA
      proportion (P = 0.04) and the ratio of AA/linoleic acid (LA, 18:2omega6) (P =
      0.004) in serum phospholipids of controls. The APOA5-1131C allele was associated
      with lower AA (P = 0.027) and AA/LA (P = 0.014) only in controls carrying the
      FEN1 10154T allele. In conclusion, the interaction between these genes suggests
      that the FEN1 10154T variant allele decreases AA and AA/LA in the serum
      phospholipids of carriers of the APOA5-1131C allele, but contributes no
      significant increase in CAD risk for this population subset despite their
      increased triglylcerides and decreased apoA5.

PMID- 20802162
TI  - Negative and positive predictive value of a whole-blood interferon-gamma release
      assay for developing active tuberculosis: an update.
AB  - RATIONALE: only limited data are available on the predictive value of interferon
      gamma release assays for progression from latent tuberculosis infection to active
      tuberculosis (TB). OBJECTIVES: to build on our initial study comparing the
      QuantiFERON-TB Gold in-tube assay (QFT) with the tuberculin skin test (TST) in
      close contacts of patients with TB and evaluating progression to active TB for up
      to 4 years. METHODS: a cohort of close contacts of smear-positive index cases
      established between May 2005 and April 2008 was tested with QFT and TST. Through
      April 2010, progressors to active TB were consecutively recorded. MEASUREMENTS
      AND MAIN RESULTS: of the 1,414 contacts (141 children), 1,033 were still resident
      in Hamburg at the end of the study period, and results of both tests were
      available for 954. QFT, but not TST, results were associated with exposure time
      (P < 0.0001). For QFT, 198 of 954 (20.8%) were positive; 63.3% (604) were TST
      positive at greater than 5 mm and 25.4% at greater than 10 mm. Nine hundred and
      three contacts refused chemoprevention and 19 developed active TB. All 19 (100%)
      had been QFT positive with a progression rate of 12.9% (19 of 147) over the
      observation period. Corresponding values for the TST were significantly lower:
      89.5% (17 of 19) and 3.1% (17 of 555) at greater than 5 mm, and 52.6% (10 of 19)
      and 4.8% (10 of 207) at greater than 10 mm, respectively. The progression rate of
      28.6% (6 of 21) for QFT-positive children was significantly higher than 10.3% (13
      of 126) for adults (P = 0.03). CONCLUSIONS: results suggest that QFT is more
      reliable than the TST for identifying those who will soon progress to active TB,
      especially in children.

PMID- 20802163
TI  - Genetic variation in the glutathione synthesis pathway, air pollution, and
      children's lung function growth.
AB  - RATIONALE: Glutathione plays an important role in antioxidant and inflammatory
      processes in the lung. Alterations in glutathione metabolism are a central
      feature of several chronic lung diseases. OBJECTIVES: To determine whether
      sequence variation in genes in the glutathione synthesis pathway alters
      susceptibility to air pollution effects on lung function. METHODS: In this
      prospective study, 14,821 lung function measurements were taken on 2,106 children
      from 12 Southern California cities. Tagging single-nucleotide polymorphisms in
      glutathione metabolism pathway genes GSS, GSR, GCLM, and GCLC were genotyped by
      GoldenGate assay (Illumina, San Diego, CA). Mixed regression models were used to
      determine whether particular haplotypes were associated with FEV(1), maximal mid
      expiratory flow rate, and FVC and whether any of the genetic associations varied
      with levels of exposure to air pollutants. MEASUREMENTS AND MAIN RESULTS: We
      found that variation in the GSS locus was associated with differences in
      susceptibility of children for lung function growth deficits associated with
      NO(2), PM(10), PM(2.5), elemental carbon, organic carbon, and O(3). The negative
      effects of air pollutants were largely observed within participants who had a
      particular GSS haplotype. The effects ranged from -124.2 to -149.1 for FEV(1),
      from -92.9 to -126.7 for FVC, and from -193.9 to -277.9 for maximal mid
      expiratory flow rate for all pollutants except O(3), which showed a larger
      decrease in lung function in children without this haplotype. CONCLUSIONS:
      Variation in GSS was associated with differences in susceptibility to adverse
      effects of pollutants on lung function growth.

PMID- 20802165
TI  - Written action plan in pediatric emergency room improves asthma prescribing,
      adherence, and control.
AB  - RATIONALE: An acute-care visit for asthma often signals a management failure.
      Although a written action plan is effective when combined with self-management
      education and regular medical review, its independent value remains
      controversial. OBJECTIVES: We examined the efficacy of providing a written action
      plan coupled with a prescription (WAP-P) to improve adherence to medications and
      other recommendations in a busy emergency department. METHODS: We randomized 219
      children aged 1-17 years to receive WAP-P (n = 109) or unformatted prescription
      (UP) (n = 110). All received fluticasone and albuterol inhalers, fitted with dose
      counters, to use at the discretion of the emergency physician. The main outcome
      was adherence to fluticasone (use/prescribed * 100%) over 28 days. Secondary
      outcomes included pharmacy dispensation of oral corticosteroids, beta(2)-agonist
      use, medical follow-up, asthma education, acute-care visits, and control.
      MEASUREMENTS AND MAIN RESULTS: Although both groups showed a similar drop in
      adherence in the initial 14 days, adherence to fluticasone was significantly
      higher over Days 15-28 in children receiving WAP-P (mean group difference, 16.13%
      [2.09, 29.91]). More WAP-P than UP patients filled their oral corticosteroid
      prescription (relative risk, 1.31 [1.07, 1.60]) and were well-controlled at 28
      days (1.39 [1.04, 1.86]). Compared with UP, use of WAP-P increased physicians'
      prescription of maintenance fluticasone (2.47 [1.53, 3.99]) and recommendation
      for medical follow-up (1.87 [1.48, 2.35]), without group differences in other
      outcomes. CONCLUSIONS: Provision of a written action plan significantly increased
      patient adherence to inhaled and oral corticosteroids and asthma control and
      physicians' recommendation for maintenance fluticasone and medical follow-up,
      supporting its independent value in the acute-care setting. Clinical trial
      registered with www.clinicaltrials.gov (NCT 00381355).

PMID- 20802166
TI  - The influence of neonatal lung function on rhinovirus-associated wheeze.
AB  - RATIONALE: Several studies have shown that the occurrence of wheezing illnesses
      during the first year of life is associated with lower levels of lung function
      shortly after birth and before any respiratory illness. It has been suggested
      that reduced lung function early in life predisposes infants to wheezing during
      viral respiratory infections, but the association between neonatal lung function
      and subsequent confirmed viral infections has never been investigated.
      OBJECTIVES: To study the influence between neonatal lung function and the
      occurrence of human rhinovirus (HRV)-associated wheeze. METHODS: In a prospective
      birth cohort study, infants were followed from birth through the first year of
      life with daily questionnaires about respiratory symptoms. Neonatal lung function
      was performed within the first 2 months of life. Nose and throat swabs were
      collected during episodes with respiratory symptoms. Polymerase chain reaction
      was used to detect single HRV infections. MEASUREMENTS AND MAIN RESULTS: In 176
      of the 202 infants (87%) with a single HRV infection, valid lung function
      measurements were obtained. The risk of wheeze was 1.49 times higher for each SD
      increase of airway resistance. The adjusted risk (corrected for possible
      important confounders) for wheeze was 1.77 (95% confidence interval, 1.16-2.69; P
      = 0.01) times higher for each SD increase of airway resistance. Maternal smoking
      during pregnancy was independently associated with wheeze (odds ratio 4.42; 95%
      confidence interval, 1.27-15.5; P = 0.02). CONCLUSIONS: This study showed that
      total lung resistance is clearly associated with HRV-associated wheeze. Moreover,
      HRV-associated wheeze might be the first sign to recognize infants with reduced
      neonatal lung function.

PMID- 20802164
TI  - Early identification of patients at risk of acute lung injury: evaluation of lung
      injury prediction score in a multicenter cohort study.
AB  - RATIONALE: Accurate, early identification of patients at risk for developing
      acute lung injury (ALI) provides the opportunity to test and implement secondary
      prevention strategies. OBJECTIVES: To determine the frequency and outcome of ALI
      development in patients at risk and validate a lung injury prediction score
      (LIPS). METHODS: In this prospective multicenter observational cohort study,
      predisposing conditions and risk modifiers predictive of ALI development were
      identified from routine clinical data available during initial evaluation. The
      discrimination of the model was assessed with area under receiver operating curve
      (AUC). The risk of death from ALI was determined after adjustment for severity of
      illness and predisposing conditions. MEASUREMENTS AND MAIN RESULTS: Twenty-two
      hospitals enrolled 5,584 patients at risk. ALI developed a median of 2
      (interquartile range 1-4) days after initial evaluation in 377 (6.8%; 148 ALI
      only, 229 adult respiratory distress syndrome) patients. The frequency of ALI
      varied according to predisposing conditions (from 3% in pancreatitis to 26% after
      smoke inhalation). LIPS discriminated patients who developed ALI from those who
      did not with an AUC of 0.80 (95% confidence interval, 0.78-0.82). When adjusted
      for severity of illness and predisposing conditions, development of ALI increased
      the risk of in-hospital death (odds ratio, 4.1; 95% confidence interval, 2.9
      5.7). CONCLUSIONS: ALI occurrence varies according to predisposing conditions and
      carries an independently poor prognosis. Using routinely available clinical data,
      LIPS identifies patients at high risk for ALI early in the course of their
      illness. This model will alert clinicians about the risk of ALI and facilitate
      testing and implementation of ALI prevention strategies. Clinical trial
      registered with www.clinicaltrials.gov (NCT00889772).

PMID- 20802167
TI  - Will the electronic medical record live up to its promise?

PMID- 20802168
TI  - The right ventricle in pulmonary hypertension: from dogma to data.

PMID- 20802169
TI  - An official American Thoracic Society public policy statement: Novel risk factors
      and the global burden of chronic obstructive pulmonary disease.
AB  - RATIONALE: Although cigarette smoking is the most important cause of chronic
      obstructive pulmonary disease (COPD), a substantial proportion of COPD cases
      cannot be explained by smoking alone. OBJECTIVES: To evaluate the risk factors
      for COPD besides personal cigarette smoking. METHODS: We constituted an ad hoc
      subcommittee of the American Thoracic Society Environmental and Occupational
      Health Assembly. An international group of members was invited, based on their
      scientific expertise in a specific risk factor for COPD. For each risk factor
      area, the committee reviewed the literature, summarized the evidence, and
      developed conclusions about the likelihood of it causing COPD. All conclusions
      were based on unanimous consensus. MEASUREMENTS AND MAIN RESULTS: The population
      attributable fraction for smoking as a cause of COPD ranged from 9.7 to 97.9%,
      but was less than 80% in most studies, indicating a substantial burden of disease
      attributable to nonsmoking risk factors. On the basis of our review, we concluded
      that specific genetic syndromes and occupational exposures were causally related
      to the development of COPD. Traffic and other outdoor pollution, secondhand
      smoke, biomass smoke, and dietary factors are associated with COPD, but
      sufficient criteria for causation were not met. Chronic asthma and tuberculosis
      are associated with irreversible loss of lung function, but there remains
      uncertainty about whether there are important phenotypic differences compared
      with COPD as it is typically encountered in clinical settings. CONCLUSIONS: In
      public health terms, a substantive burden of COPD is attributable to risk factors
      other than smoking. To prevent COPD-related disability and mortality, efforts
      must focus on prevention and cessation of exposure to smoking and these other,
      less well-recognized risk factors.

PMID- 20802170
TI  - Checking zero calibration of the HypAir FeNO.

PMID- 20802171
TI  - Bronchial thermoplasty in developing countries: is it really worth it?

PMID- 20802172
TI  - Does lung cancer screening with low-dose CT remain promising despite
      disappointing DANTE results?

PMID- 20802173
TI  - SCG10 expression on activation of hepatic stellate cells promotes cell motility
      through interference with microtubules.
AB  - During liver fibrogenesis, quiescent hepatic stellate cells switch their
      phenotype toward a myofibroblastic-like pattern with a gain in motility. Here, we
      show that SCG10 (superior cervical ganglia 10) mRNA expression, a microtubule
      destabilizing protein that favors cell growth and motility in neurons, both
      increases and correlates with the stage of fibrosis in patients with chronic
      hepatitis C. We also show the de novo expression of SCG10 mRNA in two rat models
      of liver fibrosis. We demonstrate that activated hepatic stellate cells appear to
      be the major cellular sources of SCG10 in the liver. Tracking of the SCG10
      pathway in hepatic stellate cells shows that SCG10 initially accumulates in the
      perinuclear Golgi area then migrates in small vesicle-like structures along
      individual microtubules. Moreover, SCG10 vesicles cluster at the distal ends of
      microtubules in areas where tubules are spread and decompacted, suggesting their
      preferential association with destabilized and dynamic microtubules. Inhibition
      of SCG10 expression by gene-specific short interfering RNA in primary rat hepatic
      stellate cells is associated with a significant reduction in microtubule
      dependent cellular functions, such as proliferation and migration. In conclusion,
      the de novo expression of SCG10 by hepatic stellate cells may play a major role
      in cellular mechanisms associated with HSC activation, namely cell motility and
      division, through interference with microtubules. SCG10 may represent a potential
      molecular target for anti-fibrosis therapies.

PMID- 20802174
TI  - Cytomegalovirus infection leads to microvascular dysfunction and exacerbates
      hypercholesterolemia-induced responses.
AB  - Cytomegalovirus (CMV) persistently infects more than 60% of the worldwide
      population. In immunocompetent hosts, it has been implicated in several diseases,
      including cardiovascular disease, possibly through the induction of inflammatory
      pathways. Cardiovascular risk factors promote an inflammatory phenotype in the
      microvasculature long before clinical disease is evident. This study determined
      whether CMV also impairs microvascular homeostasis and synergizes with
      hypercholesterolemia to exaggerate these responses. Intravital microscopy was
      used to assess endothelium-dependent and -independent arteriolar vasodilation and
      venular leukocyte and platelet adhesion in mice after injection with either mock
      inoculum or murine CMV (mCMV). Mice were fed a normal (ND) or high-cholesterol
      (HC) diet beginning at 5 weeks postinfection (p.i.), or a HC diet for the final 4
      weeks of infection. mCMV-ND mice exhibited impaired endothelium-dependent
      vasodilation versus mock-ND at 9 and 12 weeks and endothelium-independent
      arteriolar dysfunction by 24 weeks. Transient mild leukocyte adhesion occurred in
      mCMV-ND venules at 7 and 21 weeks p.i. HC alone caused temporary arteriolar
      dysfunction and venular leukocyte and platelet recruitment, which were
      exaggerated and prolonged by mCMV infection. The time of introduction of HC after
      mCMV infection determined whether mCMV+HC led to worse venular inflammation than
      either factor alone. These findings reveal a proinflammatory influence of
      persistent mCMV on the microvasculature, and suggest that mCMV infection enhances
      microvasculature susceptibility to both inflammatory and thrombogenic responses
      caused by hypercholesterolemia.

PMID- 20802175
TI  - Trophoblast- and vascular smooth muscle cell-derived MMP-12 mediates elastolysis
      during uterine spiral artery remodeling.
AB  - During the first trimester of pregnancy, the uterine spiral arteries are
      remodeled, creating heavily dilated conduits that lack maternal vasomotor control
      but allow the placenta to meet an increasing requirement for nutrients and
      oxygen. To effect permanent vasodilatation, the internal elastic lamina and
      medial elastin fibers must be degraded. In this study, we sought to identify the
      elastolytic proteases involved in this process. Primary first-trimester
      cytotrophoblasts (CTBs) derived from the placenta exhibited intracellular and
      membrane-associated elastase activity; membrane-associated activity was primarily
      attributable to matrix metalloproteinases (MMP). Indeed, Affymetrix microarray
      analysis and immunocytochemistry implicated MMP-12 (macrophage metalloelastase)
      as a key mediator of elastolysis. Cultured human aortic smooth muscle cells
      (HASMCs) exhibited constitutive membrane-associated elastase activity and
      inducible intracellular elastase activity; these cells also expressed MMP-12
      protein. Moreover, a specific inhibitor of MMP-12 significantly reduced CTB- and
      HASMC-mediated elastolysis in vitro, to 31.7 +/- 10.9% and 23.3 +/- 8.7% of
      control levels, respectively. MMP-12 is expressed by both interstitial and
      endovascular trophoblasts in the first-trimester placental bed and by vascular
      SMCs (VSMCs) in remodeling spiral arteries. Perfusion of isolated spiral artery
      segments with CTB-conditioned medium stimulated MMP-12 expression in medial
      VSMCs. Our data support a model in which trophoblasts and VSMCs use MMP-12
      cooperatively to degrade elastin during vascular remodeling in pregnancy, with
      the localized release of elastin peptides and CTB-derived factors amplifying
      elastin catabolism.

PMID- 20802176
TI  - The role of vascular endothelial growth factor-induced activation of NADPH
      oxidase in choroidal endothelial cells and choroidal neovascularization.
AB  - Rac1, a subunit of NADPH oxidase, plays an important role in directed endothelial
      cell motility. We reported previously that Rac1 activation was necessary for
      choroidal endothelial cell migration across the retinal pigment epithelium, a
      critical step in the development of vision-threatening neovascular age-related
      macular degeneration. Here we explored the roles of Rac1 and NADPH oxidase
      activation in response to vascular endothelial growth factor treatment in vitro
      and in a model of laser-induced choroidal neovascularization. We found that
      vascular endothelial growth factor induced the activation of Rac1 and of NADPH
      oxidase in cultured human choroidal endothelial cells. Further, vascular
      endothelial growth factor led to heightened generation of reactive oxygen species
      from cultured human choroidal endothelial cells, which was prevented by the NADPH
      oxidase inhibitors, apocynin and diphenyleneiodonium, or the antioxidant, N
      acetyl-L-cysteine. In a model of laser-induced injury, inhibition of NADPH
      oxidase with apocynin significantly reduced reactive oxygen species levels as
      measured by dihydroethidium fluorescence and the volume of laser-induced
      choroidal neovascularization. Mice lacking functional p47phox, a subunit of NADPH
      oxidase, had reduced dihydroethidium fluorescence and choroidal
      neovascularization compared with wild-type controls. Taken together, these
      results indicate that vascular endothelial growth factor activates Rac1 upstream
      from NADPH oxidase in human choroidal endothelial cells and increases generation
      of reactive oxygen species, contributing to choroidal neovascularization. These
      steps may contributed to the pathology of neovascular age-related macular
      degeneration.

PMID- 20802177
TI  - FTY720 regulates bone marrow egress of eosinophils and modulates late-phase skin
      reaction in mice.
AB  - Eosinophilia in the blood and skin is frequently observed in patients with
      certain inflammatory skin diseases, such as atopic dermatitis. However, the
      mechanism underlying eosinophil circulation and the role of eosinophils in
      cutaneous immune responses remain unclear. In repeated hapten application-induced
      cutaneous responses in BALB/c mice, the administration of FTY720 before the last
      challenge decreased the number of skin-infiltrating eosinophils and reduced the
      late-phase reaction. A similar reduction of the late-phase reaction was observed
      by a sphingosine-1-phosphate G protein-coupled receptor (S1P1)-selective agonist,
      SEW2871. We monitored numerous alterations of eosinophils in the blood, spleen,
      bone marrow, and lymph nodes of interleukin-5 transgenic mice, used as an
      eosinophilia model, following FTY720 administration. The number of circulating
      eosinophils was significantly decreased after treatment with FTY720, and
      eosinophils accumulated in the bone marrow. In addition, eosinophils expressed
      S1P1, S1P3, and S1P4 mRNAs, and their chemotactic response to S1P was abolished
      by FTY720 as well as by SEW2871. These findings suggest that FTY720 affects the
      number of eosinophils in both the blood and skin by inhibiting the egress of
      eosinophils from the bone marrow and thus downmodulating the late-phase reaction.

PMID- 20802178
TI  - TLR2-mediated expansion of MDSCs is dependent on the source of tumor exosomes.
AB  - Exosomes released from tumor cells having been shown to induce interleukin-6
      release from myeloid-derived suppressor cells in a Toll-like receptor 2/Stat3
      dependent manner. In this study, we show that exosomes released from tumor cells
      re-isolated from syngeneic mice are capable of inducing interleukin-6 in a Toll
      like receptor 2-independent manner, whereas the data generated from exosomes of
      tumor cells having undergone numerous in vitro passages induce interleukin-6 in a
      Toll-like receptor 2-dependent manner. This discrepancy may be due to the source
      of tumor cells used to generate the exosomes for this study. These results
      suggest that exosomes released from tumor cells that are not within a tumor
      microenvironment may not realistically represent the role of tumor exosomes in
      vivo. This is an important consideration since frequently passing tumor cells in
      vivo is an accepted practice for studying tumor exosome-mediated inflammatory
      responses.

PMID- 20802180
TI  - Adaptive calcified matrix response of dental pulp to bacterial invasion is
      associated with establishment of a network of glial fibrillary acidic
      protein+/glutamine synthetase+ cells.
AB  - We report evidence for anatomical and functional changes of dental pulp in
      response to bacterial invasion through dentin that parallel responses to noxious
      stimuli reported in neural crest-derived sensory tissues. Sections of resin
      embedded carious adult molar teeth were prepared for immunohistochemistry, in
      situ hybridization, ultrastructural analysis, and microdissection to extract mRNA
      for quantitative analyses. In odontoblasts adjacent to the leading edge of
      bacterial invasion in carious teeth, expression levels of the gene encoding
      dentin sialo-protein were 16-fold greater than in odontoblasts of healthy teeth,
      reducing progressively with distance from this site of the carious lesion. In
      contrast, gene expression for dentin matrix protein-1 by odontoblasts was
      completely suppressed in carious teeth relative to healthy teeth. These changes
      in gene expression were related to a gradient of deposited reactionary dentin
      that displayed a highly modified structure. In carious teeth, interodontoblastic
      dentin sialo-protein(-) cells expressing glutamine synthetase (GS) showed up
      regulation of glial fibrillary acidic protein (GFAP). These cells extended
      processes that associated with odontoblasts. Furthermore, connexin 43 established
      a linkage between adjacent GFAP(+)/GS(+) cells in carious teeth only. These
      findings indicate an adaptive pulpal response to encroaching caries that includes
      the deposition of modified, calcified, dentin matrix associated with networks of
      GFAP(+)/GS(+) interodontoblastic cells. A regulatory role for the networks of
      GFAP(+)/GS(+) cells is proposed, mediated by the secretion of glutamate to
      modulate odontoblastic response.

PMID- 20802179
TI  - Focal adhesion assembly in myofibroblasts fosters a microenvironment that
      promotes tumor growth.
AB  - Cells within the tumor microenvironment influence tumor growth through multiple
      mechanisms. Pericytes such as hepatic stellate cells are an important cell within
      the tumor microenvironment; their transformation into highly motile
      myofibroblasts leads to angiogenesis, stromal cell recruitment, matrix
      deposition, and ensuing tumor growth. Thus, a better understanding of mechanisms
      that regulate motility of pericytes is required. Focal adhesions (FAs) form a
      physical link between the extracellular environment and the actin cytoskeleton, a
      requisite step for cell motility. FAs contain a collection of proteins including
      the Ena/VASP family member, vasodilator-stimulated phosphoprotein (VASP);
      however, a role for VASP in FA development has been elusive. Using a
      comprehensive siRNA knockdown approach and a variety of VASP mutants coupled with
      complementary cell imaging methodologies, we demonstrate a requirement of VASP
      for optimal development of FAs and cell spreading in LX2 liver myofibroblasts,
      which express high levels of endogenous VASP. Rac1, a binding partner of VASP,
      acts in tandem with VASP to regulate FAs. In vivo, perturbation of Ena/VASP
      function in tumor myofibroblast precursor cells significantly reduces pericyte
      recruitment to tumor vasculature, myofibroblastic transformation, tumor
      angiogenesis, and tumor growth, providing in vivo pathobiologic relevance to
      these findings. Taken together, our results identify Ena/VASP as a significant
      modifier of tumor growth through regulation of FA dynamics and ensuing
      pericyte/myofibroblast function within the tumor microenvironment.

PMID- 20802181
TI  - BRAF mutation is rare in advanced-stage low-grade ovarian serous carcinomas.
AB  - Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous
      borderline tumor-serous carcinoma sequence. In this study, we found that advanced
      stage, low-grade ovarian serous carcinomas both with and without adjacent serous
      borderline tumor shared similar regions of loss of heterozygosity. We then
      analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53
      mutations were not detected in any serous borderline tumors (n = 30) or low-grade
      serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas
      (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous
      borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2
      stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a
      KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade
      serous carcinomas, which contrasts with previous findings, suggests that
      aggressive, low-grade serous carcinomas are more likely derived from serous
      borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade
      carcinoma patients with BRAF or KRAS mutation have a better apparent clinical
      outcome. However, further investigation is needed.

PMID- 20802182
TI  - A{beta} accelerates the spatiotemporal progression of tau pathology and augments
      tau amyloidosis in an Alzheimer mouse model.
AB  - Senile plaques formed by beta-amyloid peptides (Abeta) and neurofibrillary
      tangles (NFTs) formed by hyperphosphorylated tau, a microtubule-associated
      protein, are the hallmark lesions of Alzheimer's disease (AD) in addition to loss
      of neurons. While several transgenic (Tg) mouse models have recapitulated aspects
      of AD-like Abeta and tau pathologies, a spatiotemporal mapping paradigm for
      progressive NFT accumulation is urgently needed to stage disease progression in
      AD mouse models. Braak and co-workers developed an effective and widely used NFT
      staging paradigm for human AD brains. The creation of a Braak-like spatiotemporal
      staging scheme for tau pathology in mouse models would facilitate mechanistic
      studies of AD-like tau pathology. Such a scheme would also enhance the
      reproducibility of preclinical AD therapeutic studies. Thus, we developed a novel
      murine model of Abeta and tau pathologies and devised a spatiotemporal scheme to
      stage the emergence and accumulation of NFTs with advancing age. Notably, the
      development of NFTs followed a spatiotemporal Braak-like pattern similar to that
      observed in authentic AD. More significantly, the presence of Abeta accelerated
      NFT formation and enhanced tau amyloidosis; however, tau pathology did not have
      the same effect on Abeta pathology. This novel NFT staging scheme provides new
      insights into the mechanisms of tau pathobiology, and we speculate that this
      scheme will prove useful for other basic and translational studies of AD mouse
      models.

PMID- 20802184
TI  - Endoparasitic diseases cause losses of cattle and lambs.

PMID- 20802183
TI  - Blockade of endothelin-1 with a novel series of 1,3,6-trisubstituted-2-carboxy
      quinol-4-ones controls infection-associated preterm birth.
AB  - Preterm birth (PTB) currently accounts for 13% of all births in the United
      States, with the leading cause of PTB being maternal infection. Endothelin-1, an
      extremely potent vasoconstrictor capable of increasing myometrial smooth muscle
      tone, has been shown to be up-regulated in the setting of infection in pregnancy,
      ultimately leading to PTB. In previous work, we have shown that infection
      associated PTB is controlled in our murine model by using phospharamidon, an
      endothelin-converting enzyme-1 inhibitor; knocking down endothelin-converting
      enzyme-1 mRNA; or blocking the binding of endothelin-1 to the endothelin-A
      (ET(A)) receptor with either BQ-123 or with HJP-272, the 6-OH compound of our
      series of novel synthetic (ET(A)) receptor antagonists. In the current study, we
      show that HJP-272, a highly selective ET(A) receptor antagonist with an IC(50) of
      70.1 nmol/L, binds in a noncompetitive manner to the ET(A) receptor.
      Additionally, we introduce n-propyl (HJP-286) and n-butyl (HJP-278) analogs of
      HJP-272. We find that the LD(50) of HJP-272, the analog in the series most
      effective in controlling preterm birth, is more than 20-fold higher than its
      therapeutic dose. Acute exposure to high doses of these compounds produces no
      histological changes in any organ, while chronic exposure produces only a rare
      hepatotoxic effect. These findings may be of clinical significance, as there is
      currently no FDA-approved therapy for women presenting with threatened preterm
      delivery.

PMID- 20802185
TI  - Comparison of tuberculin activity using the interferon-gamma assay for the
      diagnosis of bovine tuberculosis.
AB  - In this study, interferon-gamma (IFN-gamma) responses in whole blood cultures
      stimulated with tuberculins from different sources were compared with regard to
      their diagnostic reliability in cattle experimentally and naturally infected with
      Mycobacterium bovis. The IFN-gamma responses to different concentrations of
      purified protein derivatives (PPDs) from M bovis and Mycobacterium avium were
      quantified. Significant differences (P<0.05) between sources and concentrations
      of PPDs used for stimulation were detected, indicating a need for standardisation
      of PPDs used in the IFN-gamma assay. Additionally, a tool named'relative potency
      30' that allows rapid comparison of batches and sources of PPDs was defined.

PMID- 20802186
TI  - Human exposures to immobilising agents: results of an online survey.
AB  - Cases of human exposure to veterinary injectable anaesthetics were reviewed
      following a literature search and completion of an online questionnaire in an
      attempt to provide an objective approach to the problem. The modified Glasgow
      Coma Scale was used to rank cases according to their severity. From the cases
      examined, results showed that intoxication with potent opioids, such as
      etorphine, carfentanil and thiafentanil, need to be treated with antagonists such
      as naloxone, nalmefene or naltrexone, and not with antagonists with agonistic
      properties, such as diprenorphine. With regard to the alpha(2)-agonists xylazine,
      detomidine, medetomidine and romifidine, no antagonist is currently accredited
      for human use. Atipamezole, a specific alpha(2)-antagonist, is widely used in
      veterinary medicine and has been used experimentally to reverse dexmetomidine in
      a study in human medicine. The high concentrations of alpha(2)-agonists being
      used in zoo and wildlife medicine warrant the accreditation of atipamezole for
      use in cases of human exposure. Knowledge and availability of the appropriate
      antagonist are essential in cases of human intoxication with injectable
      anaesthetics. Preventive measures, such as wearing gloves and eye protection,
      need to be used more regularly to reduce the risk of exposure.

PMID- 20802187
TI  - Clinical and clinicopathological features of non-suppurative meningoencephalitis
      in young greyhounds in Ireland.
AB  - The clinical and clinicopathological features of non-suppurative
      meningoencephalitis in 30 greyhounds were reviewed. The dogs were from 21
      separate litters, comprised both sexes (16 males and 14 females) and ranged in
      age from five to 18 months. In 14 (66.7 per cent) litters, more than one case was
      suspected or confirmed, and the number of siblings affected within individual
      litters ranged from one to seven. Clinical signs were progressive and varied from
      five days to 12 months in duration; 12 dogs had signs of two weeks' duration or
      less. The rate of progression of signs was variable. Common features included
      dullness or lethargy (22), altered behaviour (21), proprioceptive and postural
      reaction deficits (18), circling (17), ataxia (17), decreased appetite (15) and
      weight loss (13). No consistent haematological or biochemical abnormalities were
      identified and serology failed to implicate Toxoplasma gondii or Neospora
      caninum. Cerebrospinal fluid analysis revealed mild or moderate mononuclear
      pleocytosis in 12 (70.6 per cent) of 17 dogs. No definitive antemortem diagnosis
      could be made in any affected dog.

PMID- 20802188
TI  - Thymus atrophy and regeneration following dexamethasone administration to beef
      cattle.
AB  - Thymus atrophy and regeneration were studied in 13- to 22-month-old beef calves
      treated with dexamethasone (DMT), using anabolic dosages and implementing
      different withdrawal times. Two trials were conducted. In trial 1, group A (n=6)
      received 0.7 mg/day DMT orally for 40 days, group B (n=6) received 1.4 mg/day
      orally for 40 days and group C (n=6) was the control. In trial 2, group D (n=6)
      received 0.7 mg/day DMT orally for 40 days, group E (n=6) received 1.4 mg/day
      orally for 40 days and group K (n=6) was the control. DMT withdrawal times before
      slaughter were six days (groups A and B) and 26 days (groups D and E). At
      slaughter, thymus atrophy was severe and progressive in animals from groups A and
      B. In contrast, thymus weight and volume of the animals from groups D and E were
      almost normal. Slight atrophy was also detected in the calves in these groups.
      Histological changes and Ki67 immunostaining revealed a large number of positive
      lymphoid cells, mostly in the cortical area, associated with higher expression of
      apoptosis in the medulla compared with controls. This demonstrated that the
      thymus of beef cattle is still able to regenerate following DMT administration.

PMID- 20802189
TI  - Current infection patterns of porcine proliferative enteropathy in Great Britain
      and the Republic of Ireland.

PMID- 20802190
TI  - Isolation of Enterococcus hirae from suckling rabbits with diarrhoea.

PMID- 20802194
TI  - Group B Salmonella in lungworms from a harbour porpoise (Phocoena phocoena).

PMID- 20802195
TI  - Coonhound paralysis in South Yorkshire?

PMID- 20802196
TI  - Practice involvement in OV work.

PMID- 20802197
TI  - Use of jargon.

PMID- 20802199
TI  - Brain. Editorial.

PMID- 20802198
TI  - Heat shock transcription factor 1 localizes to sex chromatin during meiotic
      repression.
AB  - Heat shock factor 1 (HSF1) is an important transcription factor in cellular
      stress responses, cancer, aging, and developmental processes including
      gametogenesis. Disruption of Hsf1, together with another HSF family member, Hsf2,
      causes male sterility and complete lack of mature sperm in mice, but the specific
      role of HSF1 in spermatogenesis has remained unclear. Here, we show that HSF1 is
      transiently expressed in meiotic spermatocytes and haploid round spermatids in
      mouse testis. The Hsf1(-/-) male mice displayed regions of seminiferous tubules
      containing only spermatogonia and increased morphological abnormalities in sperm
      heads. In search for HSF1 target genes, we identified 742 putative promoters in
      mouse testis. Among them, the sex chromosomal multicopy genes that are expressed
      in postmeiotic cells were occupied by HSF1. Given that the sex chromatin mostly
      is repressed during and after meiosis, it is remarkable that HSF1 directly
      regulates the transcription of sex-linked multicopy genes during postmeiotic
      repression. In addition, our results show that HSF1 localizes to the sex body
      prior to the meiotic divisions and to the sex chromocenter after completed
      meiosis. To the best of our knowledge, HSF1 is the first known transcription
      factor found at the repressed sex chromatin during meiosis.

PMID- 20802200
TI  - Spatiotemporal aspects of slow-waves and seizures in humans.

PMID- 20802201
TI  - Polymorphisms in ion channel genes: emerging roles in pain.

PMID- 20802202
TI  - Modulation of nocioceptive transmission with calcitonin gene-related peptide
      receptor antagonists in the thalamus.
AB  - Calcitonin gene-related peptide receptor antagonists are effective acute migraine
      treatments without the vascular contraindications associated with triptans. While
      it has been demonstrated that calcitonin gene-related peptide receptor
      antagonists act in the central nervous system, their effects in preclinical
      migraine models have been investigated in only the trigeminocervical complex.
      Migraine is a complex neurological disorder; sites in the brainstem and forebrain
      are clearly involved in its expression. We have performed electrophysiological
      recordings in thalamic neurons of rats responding to nocioceptive
      trigeminovascular inputs and tested the effect of olcegepant, a calcitonin gene
      related peptide receptor antagonist (1 mg/kg, intravenously), on cell firing. We
      further tested the effect of microiontophoresed calcitonin gene-related peptide
      and the receptor antagonists calcitonin gene-related peptide 8-37 and olcegepant
      on thalamic cell firing, elicited by stimulation of the superior sagittal sinus
      or by microiontophoretic application of l-glutamate. Additionally, we used
      immunofluorescent staining to demonstrate the presence of functional calcitonin
      gene-related peptide receptors in the ventroposteromedial thalamic nucleus by
      specifically co-staining for the calcitonin gene-related peptide receptor
      subunits calcitonin receptor-like receptor and receptor activity modifying
      protein 1. Intravenously administered olcegepant significantly inhibited cell
      firing evoked by stimulation of the superior sagittal sinus as well as the
      background activity. Microiontophoresis of calcitonin gene-related peptide 8-37
      also showed a significant inhibition of l-glutamate-evoked cell firing and firing
      evoked by stimulation of the superior sagittal sinus. Immunofluorescent staining
      confirmed the presence of the components of a functional calcitonin gene-related
      peptide receptor, the calcitonin receptor-like receptor and the receptor activity
      modifying protein 1, within the area of the ventroposteromedial thalamic nucleus.
      This is the first report on the efficacy of calcitonin gene-related peptide
      receptor antagonists at the level of third-order neurons in the migraine pathway,
      showing that the central effects of calcitonin gene-related peptide receptor
      antagonists extend beyond the trigeminocervical complex at least to the sensory
      thalamus.

PMID- 20802203
TI  - Systemic blockade of P2X3 and P2X2/3 receptors attenuates bone cancer pain
      behaviour in rats.
AB  - Pain remains an area of considerable unmet clinical need, and this is
      particularly true of pain associated with bone metastases, in part because
      existing analgesic drugs show only limited efficacy in many patients and in part
      because of the adverse side effects associated with these agents. An important
      issue is that the nature and roles of the algogens produced in bone that drive
      pain-signalling systems remain unknown. Here, we tested the hypothesis that
      adenosine triphosphate is one such key mediator through actions on P2X3 and
      P2X2/3 receptors, which are expressed selectively on primary afferent
      nocioceptors, including those innervating the bone. Using a well-established rat
      model of bone cancer pain, AF-353, a recently described potent and selective P2X3
      and P2X2/3 receptor antagonist, was administered orally to rats and found to
      produce highly significant prevention and reversal of bone cancer pain behaviour.
      This attenuation occurred without apparent modification of the disease, since
      bone destruction induced by rat MRMT-1 carcinoma cells was not significantly
      altered by AF-353. Using in vivo electrophysiology, evidence for a central site
      of action was provided by dose-dependent reductions in electrical, mechanical and
      thermal stimuli-evoked dorsal horn neuronal hyperexcitability following direct AF
      353 administration onto the spinal cord of bone cancer animals. A peripheral site
      of action was also suggested by studies on the extracellular release of adenosine
      triphosphate from MRMT-1 carcinoma cells. Moreover, elevated phosphorylated
      extracellular signal-regulated kinase expression in dorsal root ganglion neurons,
      induced by co-cultured MRMT-1 carcinoma cells, was significantly reduced in the
      presence of AF-353. These data suggest that blockade of P2X3 and P2X2/3 receptors
      on both the peripheral and central terminals of nocioceptors contributes to
      analgesic efficacy in a model of bone cancer pain. Thus, systemic P2X3 and P2X2/3
      receptor antagonists with central nervous system penetration may offer a
      promising therapeutic tool in treating bone cancer pain.

PMID- 20802205
TI  - Prosody meets syntax: the role of the corpus callosum.
AB  - Contemporary neural models of auditory language comprehension proposed that the
      two hemispheres are differently specialized in the processing of segmental and
      suprasegmental features of language. While segmental processing of syntactic and
      lexical semantic information is predominantly assigned to the left hemisphere,
      the right hemisphere is thought to have a primacy for the processing of
      suprasegmental prosodic information such as accentuation and boundary marking. A
      dynamic interplay between the hemispheres is assumed to allow for the timely
      coordination of both information types. The present event-related potential study
      investigated whether the anterior and/or posterior portion of the corpus callosum
      provide the crucial brain basis for the online interaction of syntactic and
      prosodic information. Patients with lesions in the anterior two-thirds of the
      corpus callosum connecting orbital and frontal structures, or the posterior third
      of the corpus callosum connecting temporal, parietal and occipital areas, as well
      as matched healthy controls, were tested in a paradigm that crossed syntactic and
      prosodic manipulations. An anterior negativity elicited by a mismatch between
      syntactically predicted phrase structure and prosodic intonation was analysed as
      a marker for syntax-prosody interaction. Healthy controls and patients with
      lesions in the anterior corpus callosum showed this anterior negativity
      demonstrating an intact interplay between syntax and prosody. No such effect was
      found in patients with lesions in the posterior corpus callosum, although they
      exhibited intact, prosody-independent syntactic processing comparable with
      healthy controls and patients with lesions in the anterior corpus callosum. These
      data support the interplay between the speech processing streams in the left and
      right hemispheres via the posterior portion of the corpus callosum, building the
      brain basis for the coordination and integration of local syntactic and prosodic
      features during auditory speech comprehension.

PMID- 20802204
TI  - Genetic variation influences glutamate concentrations in brains of patients with
      multiple sclerosis.
AB  - Glutamate is the main excitatory neurotransmitter in the mammalian brain.
      Appropriate transmission of nerve impulses through glutamatergic synapses is
      required throughout the brain and forms the basis of many processes including
      learning and memory. However, abnormally high levels of extracellular brain
      glutamate can lead to neuroaxonal cell death. We have previously reported
      elevated glutamate levels in the brains of patients suffering from multiple
      sclerosis. Here two complementary analyses to assess the extent of genomic
      control over glutamate levels were used. First, a genome-wide association
      analysis in 382 patients with multiple sclerosis using brain glutamate
      concentration as a quantitative trait was conducted. In a second approach, a
      protein interaction network was used to find associated genes within the same
      pathway. The top associated marker was rs794185 (P < 6.44 x 10(-7)), a non-coding
      single nucleotide polymorphism within the gene sulphatase modifying factor 1. Our
      pathway approach identified a module composed of 70 genes with high relevance to
      glutamate biology. Individuals carrying a higher number of associated alleles
      from genes in this module showed the highest levels of glutamate. These
      individuals also showed greater decreases in N-acetylaspartate and in brain
      volume over 1 year of follow-up. Patients were then stratified by the amount of
      annual brain volume loss and the same approach was performed in the 'high' (n =
      250) and 'low' (n = 132) neurodegeneration groups. The association with rs794185
      was highly significant in the group with high neurodegeneration. Further, results
      from the network-based pathway analysis remained largely unchanged even after
      stratification. Results from these analyses indicated that variance in the
      activity of neurochemical pathways implicated in neurodegeneration is explained,
      at least in part, by the inheritance of common genetic polymorphisms.
      Spectroscopy-based imaging provides a novel quantitative endophenotype for
      genetic association studies directed towards identifying new factors that
      contribute to the heterogeneity of clinical expression of multiple sclerosis.

PMID- 20802206
TI  - Subthalamic nucleus stimulation and somatosensory temporal discrimination in
      Parkinson's disease.
AB  - Whereas numerous studies document the effects of dopamine medication and deep
      brain stimulation on motor function in patients with Parkinson's disease, few
      have investigated deep brain stimulation-induced changes in sensory functions. In
      this study of 13 patients with Parkinson's disease, we tested the effects of deep
      brain stimulation on the somatosensory temporal discrimination threshold. To
      investigate whether deep brain stimulation and dopaminergic medication induce
      similar changes in somatosensory discrimination, somatosensory temporal
      discrimination threshold values were acquired under four experimental conditions:
      (i) medication ON/deep brain stimulation on; (ii) medication ON/deep brain
      stimulation off; (iii) medication OFF/deep brain stimulation on; and (iv)
      medication OFF/deep brain stimulation off. Patients also underwent clinical and
      neuropsychological evaluations during each experimental session. Somatosensory
      temporal discrimination threshold values obtained in patients were compared with
      13 age-matched healthy subjects. Somatosensory temporal discrimination threshold
      values were significantly higher in patients than in healthy subjects. In
      patients, somatosensory temporal discrimination threshold values were
      significantly lower when patients were studied in medication ON than in
      medication OFF conditions. Somatosensory temporal discrimination threshold values
      differed significantly between deep brain stimulation on and deep brain
      stimulation off conditions only when the patients were studied in the medication
      ON condition and were higher in the deep brain stimulation on/medication ON than
      in the deep brain stimulation off/medication ON condition. Dopamine but not
      subthalamic nucleus deep brain stimulation restores the altered somatosensory
      temporal discrimination in patients with Parkinson's disease. Deep brain
      stimulation degrades somatosensory temporal discrimination by modifying central
      somatosensory processing whereas dopamine restores the interplay between cortical
      and subcortical structures.

PMID- 20802207
TI  - Motor and cognitive outcome in patients with Parkinson's disease 8 years after
      subthalamic implants.
AB  - Deep brain stimulation of the subthalamic nucleus represents the most important
      innovation for treatment of advanced Parkinson's disease. Prospective studies
      have shown that although the beneficial effects of this procedure are maintained
      at 5 years, axial motor features and cognitive decline may occur in the long term
      after the implants. In order to address some unsolved questions raised by
      previous studies, we evaluated a series of 20 consecutive patients who received
      continuous stimulation for 8 years. The overall motor improvement reported at 5
      years (55.5% at Unified Parkinson's Disease Rating Scale-motor part, P < 0.001
      compared with baseline) was only partly retained 3 years later (39%, P < 0.001,
      compared with baseline; -16.5%, P < 0.01, compared with 5 years), with
      differential effects on motor features: speech did not improve and postural
      stability worsened (P < 0.05). The preoperative levodopa equivalent daily dose
      was reduced by 58.2% at 5 years and by 60.3% at 8 years. In spite of subtle
      worsening of motor features, a dramatic impairment in functional state (-56.6% at
      Unified Parkinson's Disease Rating Scale-Activities of Daily Living, P < 0.01)
      emerged after the fifth year of stimulation. The present study did not reveal a
      predictive value of preoperative levodopa response, whereas few single features
      at baseline (such as gait and postural stability motor scores and the
      preoperative levodopa equivalent daily dose) could predict long-term motor
      outcome. A decline in verbal fluency (slightly more pronounced than after 5
      years) was detected after 8 years. A significant but slight decline in tasks of
      abstract reasoning, episodic memory and executive function was also found. One
      patient had developed dementia at 5 years with further progression at 8 years.
      Executive dysfunction correlated significantly with postural stability,
      suggesting interplay between axial motor deterioration and cognition. Eight years
      after surgery, no significant change was observed on scales assessing depression
      or anxiety when compared with baseline. At 8 years, there was no significant
      increase of side-effects when compared with 5-year follow-up. In conclusion, deep
      brain stimulation of the subthalamic nucleus is a safe procedure with regard to
      cognitive and behavioural morbidity over long-term follow-up. However, the global
      benefit partly decreases later in the course of the disease, due to progression
      of Parkinson's disease and the appearance of medication- and stimulation
      resistant symptoms.

PMID- 20802208
TI  - Preferential use of protein domain pairs as interaction mediators: order and
      transitivity.
AB  - MOTIVATION: Many protein-protein interactions (PPIs) are mediated by protein
      domains. The structural data of multi-domain PPIs reveal the domain pair (or
      pairs) that mediate a PPI, and implicitly also the domain pairs that are not
      involved in the interaction. By analyzing such data, preference relations between
      domain pairs as interaction mediators may be revealed. RESULTS: Here, we analyze
      the differential use of domain pairs as mediators of stable interactions based on
      structurally solved multi-domain protein complexes. Our analysis revealed domain
      pairs that are preferentially used as interaction mediators and domain pairs that
      rarely or never mediate interaction, independent of the proteins' context.
      Between these extremes, there are domain pairs that mediate protein interaction
      in some protein contexts, while in other contexts different domain pairs
      predominate over them. By describing the preference relations between domain
      pairs as a network, we uncovered partial order and transitivity in these
      relations, which we further exploited for predicting interaction-mediating
      domains. The preferred domain pairs and the ones over which they predominate
      differ in several properties, but these differences cannot yet determine
      explicitly what underlies the differential use of domain pairs as interaction
      mediators. One property that stood up was the over-abundance of homotypic
      interactions among the preferred domain pairs, supporting previous suggestions on
      the advantages in the use of domain self-interaction for mediating protein
      interactions. Finally, we show a possible association between the preferred
      domain pairs and the function of the complex where they reside. CONTACT:
      hanahm@ekmd.huji.ac.il SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 20802209
TI  - XMSF: Structure-preserving noise reduction and pre-segmentation in microscope
      tomography.
AB  - SUMMARY: Interpretation of electron tomograms is difficult due to the high noise
      levels. Thus, denoising techniques are needed to improve the signal-to-noise
      ratio. XMSF (Microscopy Mean Shift Filtering) is a fast, user-friendly
      application that succeeds in filtering noise while preserving the structures of
      interest. It is based on the extension to 3D of a method widely applied in other
      image processing fields under very different scenarios. XMSF has been tested for
      a variety of tomograms, showing a great potential to become a state-of-the-art
      filtering program in electron tomography. Applied iteratively, the algorithm
      yields pre-segmented volumes facilitating posterior segmentation tasks. Moreover,
      execution times remain low thanks to parallel computing techniques to exploit
      current multicore computers. AVAILABILITY:
      http://sites.google.com/site/xmsfilter/

PMID- 20802210
TI  - Idiopathic generalised epilepsy of late onset: a separate nosological entity?
AB  - AIM: Seizure onset in idiopathic generalised epilepsies (IGE) is considered to be
      rare after the second decade of life. The authors aimed to explore age of seizure
      onset in patients with IGE and compare 'classical' onset to late onset cases.
      METHODS: Patients with IGE, treated at the outpatient epilepsy clinic (Medical
      University of Innsbruck, Austria, 1985-2006, n=798) were retrospectively
      screened. The inclusion criteria were: diagnosis of IGE, more than two follow-up
      (FU) visits, duration of FU more than 1 year and normal brain imaging. The
      authors analysed demographic data, age of seizure onset, seizure types,
      syndromes, neuroimaging and EEG findings, seizure triggers and seizure freedom
      for 1 and 5 years at last FU. RESULTS: A total of 492 patients (mean age at
      seizure onset 14.6 years, range 0.1-55, SD 7.9) with IGE were identified:
      childhood absence epilepsy (n=113, range 1-55, SD 6.5), juvenile absence epilepsy
      (n=75, range 4-39, SD 5.1), juvenile myoclonic epilepsy (n=112, range 2-39, SD
      5.7), and epilepsy with grand mal seizures on awakening (n=192 range 1-52, SD
      17.3). Population was stratified into three groups: 28 patients with seizure
      onset at >30 years, 180 patients between 15 and 30 years and 284 patients <15
      years. The distribution of seizure types and epilepsy syndromes differed
      significantly in a group comparison (p<0.001); seizure outcome and other clinical
      variables did not differ throughout the groups. CONCLUSION: Apart from age
      related onset of seizure types and syndromes with a loose upper limit of onset
      age, patients with a late onset did not differ from their younger counterparts.
      These data do not support the view of IGE of late onset as a separate syndrome.

PMID- 20802211
TI  - Development and validation of a short version of the Stroke Specific Quality of
      Life Scale.
AB  - BACKGROUND AND PURPOSE: The Stroke Specific Quality of Life Scale (SS-QoL) is a
      well validated measure of health related quality of life in patients with stroke,
      but with 49 items its length is a disadvantage. A short version of the SS-QoL was
      developed and tested here. METHODS: Secondary analyses of three different
      studies. The short version was developed using data from 141 patients with
      aneurysmal subarachnoid haemorrhage (SAH) and tested on data from independent
      samples of 97 patients with SAH and 105 patients with ischaemic stroke or
      intracerebral haemorrhage. The item with the highest item domain correlation from
      each of the SS-QoL domains was selected to obtain a 12 item SS-QoL (SS-QoL-12)
      with a total score and physical and psychosocial subscores. Criterion validity of
      the SS-QoL-12 scores was tested in each sample with the original SS-QoL as
      reference. RESULTS: All three scores of the SS-QoL-12 showed good internal
      consistency (Cronbach's alpha 0.77-0.89). The SS-Qol-12 scores predicted 88-95%
      of the variance of the original SS-QoL. Mean differences between the SS-QoL-12
      and SS-QoL and their 95% CI were generally within 0.1 points on a 1-5 scale. The
      limits of agreement were generally within 0.4 points. CONCLUSION: The SS-QoL-12
      has good criterion validity for all subsets of stroke. Because it consists of
      only 12 questions, this short form will be easy to use in research and clinical
      settings.

PMID- 20802212
TI  - Pallidal neuronal discharge in Parkinson's disease following intraputamenal fetal
      mesencephalic allograft.
AB  - BACKGROUND: Human intrastriatal fetal allografts survive over long periods of
      time in the brains of Parkinson's disease (PD) patients and integrate into host
      circuitry. However, some grafted patients with a prior history of levodopa
      induced dyskinesias have developed off-medication dyskinesias and dystonias
      following allografting whose mechanism remains poorly understood. The authors
      present single-unit discharge characteristics in the external and internal globus
      pallidus (GPe and GPi) in an awake patient with PD undergoing microelectrode
      guided surgery for pallidal deep brain stimulation, 10 years following bilateral
      intraputamenal fetal mesencephalic allografting in an NIH-funded protocol.
      METHODS: Pallidal single-unit activity at 'rest' and during active movement was
      evaluated and compared with data sets from 13 PD patients in the 'off-medication'
      state and from one non-dyskinetic PD patient in the 'on-medication' state.
      RESULTS AND DISCUSSION: Analysis of firing rate, bursting discharge and
      oscillatory activity showed that the graft corrected some, but not all, of the
      abnormalities associated with the off-medication state. Additionally, in the
      transplanted patient, voluntary hand movement produced a marked reduction in
      pallidal discharge rate at multiple GPi recording sites, which was not observed
      during active movement in other patients. These findings are consistent with a
      persistent effect of transplanted dopamine cells on basal ganglia outflow and
      suggest a mechanism for the graft-induced dystonic phenotype.

PMID- 20802213
TI  - Reducing cognitive-motor declines associated with bilateral subthalamic deep
      brain stimulation through computational modelling in a Parkinson's disease
      patient.

PMID- 20802214
TI  - Impaired updating ability in drivers with Parkinson's disease.
AB  - OBJECTIVE: Driving activity requires major involvement of executive functions.
      The main objective of our study was to determine whether mental flexibility and
      the updating of information in working memory are affected in drivers with mild
      to moderate Parkinson's disease (PD). METHODS: The study included 25 patients,
      aged 58-76, with mild to moderate PD and 25 healthy controls matched for age, sex
      and education, with an average mileage of over 3000 km/year. Neuropsychological
      tests were conducted to assess global cognitive abilities, to evaluate updating
      (via the n-back task), flexibility (via the plus-minus task) and information
      processing speed (via the Stroop test). Three different scenarios were developed
      on a driving simulator. Participants were asked to recall road signs (updating
      task), indicate the shape or colour of road signs according to road side
      (flexibility task) and to brake at the same time as the car ahead (information
      processing speed task) while driving. RESULTS: An updating impairment was found
      in PD patients in the n-back and simulator tasks; patients recalled significantly
      fewer road signs. No notable differences were observed between groups in the plus
      minus task or in the simulator task evaluating flexibility. There was no
      significant difference between patients and controls in information-processing
      speed tasks. Regression analysis showed that the Trail-Making test (B-A)
      accounted for 40.7% of the variation in PD drivers' simulator task updating
      score. CONCLUSION: The updating function is clearly impaired in drivers with mild
      to moderate PD, while mental flexibility remains unaffected. This study
      demonstrates the interest of using the Trail Making Test and simulator tasks to
      assess PD drivers.

PMID- 20802215
TI  - Cerebrospinal fluid biomarkers in the differential diagnosis of Alzheimer's
      disease from other cortical dementias.
AB  - BACKGROUND: Considering that most semantic dementia (SD) and frontotemporal
      dementia (FTD) patients show no post-mortem Alzheimer's disease (AD) pathology,
      cerebrospinal fluid (CSF) biomarkers may be of value for distinguishing these
      patients from those with AD. Additionally, biomarkers may be useful for
      identifying patients with atypical phenotypic presentations of AD, such as
      posterior cortical atrophy (PCA) and primary progressive non-fluent or logopenic
      aphasia (PNFLA). METHODS: The authors investigated CSF biomarkers (beta-amyloid 1
      42 (Abeta(42)), total tau (T-tau) and phosphorylated tau (P-tau)) in 164 patients
      with AD (n=60), PCA (n=15), behavioural variant FTD (n=27), SD (n=19), PNFLA
      (n=26) and functional cognitive disorders (FCD, n=17). The authors then examined
      the diagnostic value of these CSF biomarkers in distinguishing these patients
      from those with AD. RESULTS: The P-Tau/Abeta(42) ratio was found to be the best
      biomarker for distinguishing AD from FTD and SD, with a sensitivity of 91.7% and
      98.3%, respectively, and a specificity of 92.6% and 84.2%, respectively. As
      expected, biomarkers were less effective in differentiating AD from PNFLA and
      PCA, as significant proportions of PCA and PNFLA patients (60% and 61.5%,
      respectively) had concurrent alterations of both T-tau/Abeta(42) and P
      Tau/Abeta(42) ratios. None of the FCD patients had a typical AD CSF profile or
      abnormal T-tau/Abeta(42) or P-Tau/Abeta(42) ratios. CONCLUSION: The P
      Tau/Abeta(42) ratio is a useful tool to distinguish AD from both FTD and SD,
      which are known to involve pathological processes distinct from AD. Biomarkers
      could be useful for identifying patients with an atypical AD phenotype that
      includes PNFLA and PCA.

PMID- 20802216
TI  - Familial Alzheimer's disease and inherited prion disease in the UK are poorly
      ascertained.
AB  - AIMS: To ascertain the frequency and geographical distribution of patients
      diagnosed with known genetic causes of Alzheimer's disease (AD) and inherited
      prion disease (IPD) in the UK 2001-2005. By comparison with frequencies predicted
      from published population studies, to estimate the proportion of patients with
      these conditions who are being accurately diagnosed. METHODS: All the positive
      diagnostic test results (from both genetic testing centres) were identified for
      mutations in presenilin-1 (PSEN1), presenilin-2 (PSEN2), amyloid precursor
      protein (APP) and prion protein genes (PRNP) for patients resident in the UK in a
      5 year period. The variation in the incidence of mutation detection between UK
      regions was assessed with census population data. Published studies of the
      genetic epidemiology of familial early onset AD (EOAD) were reviewed to produce
      estimates of the number of patients in the UK that should be detected. RESULTS:
      The rate of detection of EOAD and IPD varied very significantly and consistently
      between regions of the UK with low rates of detection in Northern and Western
      Britain (72% less detection in these regions compared with Central and Southeast
      Britain). The estimates from population studies further suggest a greater number
      of patients with EOAD than are diagnosed by genetic testing throughout the UK.
      CONCLUSIONS: It is likely that patients with EOAD and IPD are not being
      recognised and referred for testing. With the prospect of meaningful disease
      modifying therapeutics for these diseases, this study highlights an issue of
      relevance to neurologists and those planning for provision of National Health
      Services.

PMID- 20802217
TI  - Mild traumatic brain injury and Postconcussion Syndrome: a neuropsychological
      perspective.
AB  - Symptoms of mild traumatic brain injury typically resolve within days or weeks.
      However, a significant group of patients may report symptoms of Post-concussional
      Syndrome (PCS) weeks, months and years postinjury. This review presents an
      overview of the pathogenesis, diagnosis and treatment options for PCS. The
      authors review the evidence for factors that may predict such symptoms. At early
      phases, there are associations between neurological signs and symptoms,
      neurocognitive functions and self reports. Over time, such associations become
      less coherent, and psychological issues become particularly relevant. An accurate
      understanding of neurological and psychosocial factors at play in PCS is crucial
      for appropriate management of symptoms at various points postinjury.

PMID- 20802219
TI  - Psychological approaches to treatment of postconcussion syndrome: a systematic
      review.
AB  - BACKGROUND AND AIM: Postconcussion syndrome (PCS) is a term used to describe the
      complex, and controversial, constellation of physical, cognitive and emotional
      symptoms associated with mild brain injury. At the current time, there is a lack
      of clear, evidence-based treatment strategies. In this systematic review, the
      authors aimed to evaluate the potential efficacy of cognitive behavioural therapy
      (CBT) and other psychological treatments in postconcussion symptoms. METHODS:
      Four electronic databases were searched up to November 2008 for studies of
      psychological approaches to treatment or prevention of postconcussion syndrome or
      symptoms. RESULTS: The search identified 7763 citations, and 42 studies were
      included. This paper reports the results of 17 randomised controlled trials for
      psychological interventions which fell into four categories: CBT for PCS or
      specific PCS symptoms; information, reassurance and education; rehabilitation
      with a psychotherapeutic element and mindfulness/relaxation. Due to heterogeneity
      of methodology and outcome measures, a meta-analysis was not possible. The
      largest limitation to our findings was the lack of high-quality studies.
      CONCLUSION: There was evidence that CBT may be effective in the treatment of PCS.
      Information, education and reassurance alone may not be as beneficial as
      previously thought. There was limited evidence that multifaceted rehabilitation
      programmes that include a psychotherapeutic element or mindfulness/relaxation
      benefit those with persisting symptoms. Further, more rigorous trials of CBT for
      postconcussion symptoms are required.

PMID- 20802218
TI  - Selective neuronal damage and Wisconsin Card Sorting Test performance in
      atherosclerotic occlusive disease of the major cerebral artery.
AB  - BACKGROUND: In atherosclerotic internal carotid artery (ICA) or middle cerebral
      artery (MCA) disease, selective neuronal damage can be detected as a decrease in
      central benzodiazepine receptors (BZRs) in the normal-appearing cerebral cortex.
      This study aimed to determine whether a decrease in the BZRs in the non-infarcted
      cerebral cortex is associated with poor performance on the Wisconsin Card Sorting
      Test (WCST), which assesses executive functions. METHODS: The authors measured
      the BZRs using positron emission tomography and (11)C-flumazenil in 60 non
      disabled patients with unilateral atherosclerotic ICA or MCA disease and no
      cortical infarction. Using three-dimensional stereotactic surface projections,
      the abnormally decreased BZR index (extent (%) of pixels with Z score >2 compared
      with controls * average Z score in those pixels) in the cerebral cortex of the
      anterior cerebral artery (ACA) or MCA territory was calculated and found to be
      correlated with the patient's score on the WCST. RESULTS: On the basis of the
      WCST results, 39 patients were considered abnormal (low categories achieved) for
      their age. The BZR index of the ACA territory in the hemisphere affected by
      arterial disease was significantly higher in abnormal patients than in normal
      patients. The BZR index of the MCA territory differed significantly between the
      two groups when patients with left arterial disease (n=28) were analysed
      separately. CONCLUSIONS: In atherosclerotic ICA or MCA disease, selective
      neuronal damage that is manifested as a decrease in BZRs in the non-infarcted
      cerebral cortex may contribute to the development of executive dysfunction.

PMID- 20802220
TI  - Critical illness myopathy is frequent: accompanying neuropathy protracts ICU
      discharge.
AB  - OBJECTIVES: Neuromuscular dysfunction in critically ill patients is attributed to
      either critical illness myopathy (CIM) or critical illness polyneuropathy (CIP)
      or a combination of both. However, it is unknown whether differential diagnosis
      has an impact on prognosis. This study investigates whether there is an
      association between the early differentiation of CIM versus CIP and clinical
      prognosis. METHODS: The authors included mechanically ventilated patients who
      featured a Simplified Acute Physiology Score II (SAPS-II) >= 20 on three
      consecutive days within the first week after intensive care unit (ICU) admission.
      Fifty-three critically ill patients were enrolled and examined by conventional
      nerve-conduction studies and direct muscle stimulation (184 examinations in
      total). The first examination was conducted within the first week after admission
      to the ICU. RESULTS: In this cohort of critically ill patients, CIM was more
      frequent (68%) than CIP (38%). Electrophysiological signs of CIM preceded
      electrophysiological signs of CIP (median at day 7 in CIM patients vs day 10 in
      CIP patients, p<0.001). Most patients with CIP featured concomitant CIM. At
      discharge from ICU, 25% of patients with isolated CIM showed electrophysiological
      signs of recovery and significantly lower degrees of weakness. Recovery could not
      be observed in patients with combined CIM/CIP, even though the ICU length of stay
      was significantly longer (mean 35 days in CIM/CIP vs mean 19 days in CIM,
      p<0.001). CONCLUSION: Prognoses of patients differ depending on
      electrophysiological findings during early critical illness: early
      electrophysiological differentiation of ICU acquired neuromuscular disorder
      enhances the evaluation of clinical prognosis during critical illness.

PMID- 20802221
TI  - Structural brain changes following peripheral vestibulo-cochlear lesion may
      indicate multisensory compensation.
AB  - BACKGROUND: Do central mechanisms account for the variability of clinical
      recovery following peripheral vestibulo-cochlear lesions? OBJECTIVE: To
      investigate structural (morphological) plasticity in the human brain following
      unilateral vestibulo-cochlear lesions which might contribute to central
      vestibular compensation. METHODS: The authors compared regional grey matter
      volume (GMV) changes in patients after surgical removal of unilateral acoustic
      neuroma with age-matched control subjects, and hypothesised morphometric changes
      in the vestibular and auditory cortices which may be related to functional
      disability scores. Patients were examined with a battery of neuro-otological
      tests and clinical scores to assess vestibular and auditory disability. RESULTS:
      Voxel-based morphometry was used for categorical comparison between patients and
      age- and gender-matched controls. GMV increase was found bilaterally in primary
      somatosensory cortices and motion-sensitive areas in the medial temporal gyrus
      (MT). Simple regression analysis revealed a GMV increase (1) in the
      contralesional superior temporal gyrus/posterior insula to be correlated with
      decreasing clinically assessed vestibular deficits; (2) in the contralesional
      inferior parietal lobe with decreasing functional impairment of daily living
      activities; and (3) in the contralesional auditory cortex (Heschl gyrus) with
      decreasing hearing impairment. CONCLUSIONS: These data may suggest structural
      cortical plasticity in multisensory vestibular cortex areas of patients with
      unilateral peripheral vestibulo-cochlear lesion after surgical removal of
      acoustic neuroma. As changes of GMV were related to vestibular function,
      structural brain changes may reflect central mechanisms of vestibular
      compensation.

PMID- 20802222
TI  - Neurological picture. Contralateral cutaneous and MRI findings in a patient with
      Parry-Romberg syndrome.

PMID- 20802223
TI  - HINKEL kinesin, ANP MAPKKKs and MKK6/ANQ MAPKK, which phosphorylates and
      activates MPK4 MAPK, constitute a pathway that is required for cytokinesis in
      Arabidopsis thaliana.
AB  - Cytokinesis is regulated to ensure the precise partitioning of cytoplasm and
      duplicated chromosomes to daughter cells. The NACK-PQR pathway, which includes
      NACK1 kinesin-like protein (KLP) and a mitogen-activated protein kinase (MAPK)
      cascade, plays a key role in cytokinesis in tobacco cells. Although
      HINKEL/AtNACK1 (HIK) KLP, ANP MAP kinase kinase kinases (MAPKKKs) and MKK6/ ANQ
      MAP kinase kinase (MAPKK) have been identified independently as regulators of
      cytokinesis in Arabidopsis thaliana, the involvement of HIK, ANPs and MKK6/ANQ in
      a regulatory cascade remains to be demonstrated. Here we provide details of the
      protein kinase pathway that controls cytokinesis in A. thaliana. Analysis of the
      subcellular distribution of six MAPKKs of A. thaliana that had been fused to
      green fluorescent protein revealed that only MKK6/ANQ protein was concentrated at
      the equatorial plane of the phragmoplast, at the site of localization of HIK.
      Expression of MKK6/ANQ in yeast cells replaced the growth-control function of the
      MAPKK encoded by yeast PBS2, provided that both ANP1 MAPKKK and HIK [or
      TETRASPORE/AtNACK2 (TES)] KLP were coexpressed, suggesting that ANP1 activates
      MKK6/ANQ in the presence of HIK (or TES). Coexpression of HIK and ANP3 (another
      member of the ANP MAPKKK family) weakly activated MKK6/ANQ but that of TES and
      ANP3 did not. MKK6/ANQ phosphorylated MPK4 MAPK in vitro to activate the latter
      kinase. Thus cytokinesis in A. thaliana is controlled by a pathway that consists
      of ANP MAPKKKs that can be activated by HIK and MKK6/ANQ MAPKK, with MPK4 MAPK
      being a probable target of MKK6/ANQ.

PMID- 20802224
TI  - CLE peptides can negatively regulate protoxylem vessel formation via cytokinin
      signaling.
AB  - Cell-cell communication is critical for tissue and organ development. In plants,
      secretory CLAVATA3/EMBRYO SURROUNDING REGION-related (CLE) peptides function as
      intercellular signaling molecules in various aspects of tissue development
      including vascular development. However, little is known about intracellular
      signaling pathways functioning in vascular development downstream of the CLE
      ligands. We show that CLE peptides including CLE10, which is preferentially
      expressed in the root vascular system, inhibit protoxylem vessel formation in
      Arabidopsis roots. GeneChip analysis displayed that CLE10 peptides repressed
      specifically the expression of two type-A Arabidopsis Response Regulators (ARRs),
      ARR5 and ARR6, whose products act as negative regulators of cytokinin signaling.
      The arr5 arr6 roots exhibited defective protoxylem vessel formation. These
      results indicate that CLE10 inhibits protoxylem vessel formation by suppressing
      the expression of type-A ARR genes including ARR5 and ARR6. This was supported by
      the finding that CLE10 did not suppress protoxylem vessel formation in a
      background of arr10 arr12, a double mutant of type-B ARR genes. Thus, our results
      revealed cross-talk between CLE signaling and cytokinin signaling in protoxylem
      vessel formation in roots. Taken together with the indication that cytokinin
      signaling functions downstream of the CLV3/WUS signaling pathway in the shoot
      apical meristem, the cross-talk between CLE and cytokinin signaling pathways may
      be a common feature in plant development.

PMID- 20802225
TI  - Reference-unbiased copy number variant analysis using CGH microarrays.
AB  - Comparative genomic hybridization (CGH) microarrays have been used to determine
      copy number variations (CNVs) and their effects on complex diseases. Detection of
      absolute CNVs independent of genomic variants of an arbitrary reference sample
      has been a critical issue in CGH array experiments. Whole genome analysis using
      massively parallel sequencing with multiple ultra-high resolution CGH arrays
      provides an opportunity to catalog highly accurate genomic variants of the
      reference DNA (NA10851). Using information on variants, we developed a new
      method, the CGH array reference-free algorithm (CARA), which can determine
      reference-unbiased absolute CNVs from any CGH array platform. The algorithm
      enables the removal and rescue of false positive and false negative CNVs,
      respectively, which appear due to the effects of genomic variants of the
      reference sample in raw CGH array experiments. We found that the CARA remarkably
      enhanced the accuracy of CGH array in determining absolute CNVs. Our method thus
      provides a new approach to interpret CGH array data for personalized medicine.

PMID- 20802226
TI  - MapSplice: accurate mapping of RNA-seq reads for splice junction discovery.
AB  - The accurate mapping of reads that span splice junctions is a critical component
      of all analytic techniques that work with RNA-seq data. We introduce a second
      generation splice detection algorithm, MapSplice, whose focus is high sensitivity
      and specificity in the detection of splices as well as CPU and memory efficiency.
      MapSplice can be applied to both short (<75 bp) and long reads (>= 75 bp).
      MapSplice is not dependent on splice site features or intron length, consequently
      it can detect novel canonical as well as non-canonical splices. MapSplice
      leverages the quality and diversity of read alignments of a given splice to
      increase accuracy. We demonstrate that MapSplice achieves higher sensitivity and
      specificity than TopHat and SpliceMap on a set of simulated RNA-seq data.
      Experimental studies also support the accuracy of the algorithm. Splice junctions
      derived from eight breast cancer RNA-seq datasets recapitulated the extensiveness
      of alternative splicing on a global level as well as the differences between
      molecular subtypes of breast cancer. These combined results indicate that
      MapSplice is a highly accurate algorithm for the alignment of RNA-seq reads to
      splice junctions. Software download URL:
      http://www.netlab.uky.edu/p/bioinfo/MapSplice.

PMID- 20802228
TI  - Cell salvage as part of a blood conservation strategy in anaesthesia.
AB  - The use of intraoperative cell salvage and autologous blood transfusion has
      become an important method of blood conservation. The main aim of autologous
      transfusion is to reduce the need for allogeneic blood transfusion and its
      associated complications. Allogeneic blood transfusion has been associated with
      increased risk of tumour recurrence, postoperative infection, acute lung injury,
      perioperative myocardial infarction, postoperative low-output cardiac failure,
      and increased mortality. We have reviewed the current evidence for cell salvage
      in modern surgical practice and examined the controversial issues, such as the
      use of cell salvage in obstetrics, and in patients with malignancy, or intra
      abdominal or systemic sepsis. Cell salvage has been demonstrated to be safe and
      effective at reducing allogeneic blood transfusion requirements in adult elective
      surgery, with stronger evidence in cardiac and orthopaedic surgery. Prolonged use
      of cell salvage with large-volume autotransfusion may be associated with dilution
      of clotting factors and thrombocytopenia, and regular laboratory or near-patient
      monitoring is required, along with appropriate blood product use. Cell salvage
      should be considered in all cases where significant blood loss (>1000 ml) is
      expected or possible, where patients refuse allogeneic blood products or they are
      anaemic. The use of cell salvage in combination with a leucocyte depletion filter
      appears to be safe in obstetrics and cases of malignancy; however, further trials
      are required before definitive guidance may be provided. The only absolute
      contraindication to the use of cell salvage and autologous blood transfusion is
      patient refusal.

PMID- 20802227
TI  - Dual role of the carboxyl-terminal region of pig liver L-kynurenine 3
      monooxygenase: mitochondrial-targeting signal and enzymatic activity.
AB  - l-kynurenine 3-monooxygenase (KMO) is an NAD(P)H-dependent flavin monooxygenase
      that catalyses the hydroxylation of l-kynurenine to 3-hydroxykynurenine, and is
      localized as an oligomer in the mitochondrial outer membrane. In the human brain,
      KMO may play an important role in the formation of two neurotoxins, 3
      hydroxykynurenine and quinolinic acid, both of which provoke severe
      neurodegenerative diseases. In mosquitos, it plays a role in the formation both
      of eye pigment and of an exflagellation-inducing factor (xanthurenic acid). Here,
      we present evidence that the C-terminal region of pig liver KMO plays a dual
      role. First, it is required for the enzymatic activity. Second, it functions as a
      mitochondrial targeting signal as seen in monoamine oxidase B (MAO B) or outer
      membrane cytochrome b(5). The first role was shown by the comparison of the
      enzymatic activity of two mutants (C-terminally FLAG-tagged KMO and carboxyl
      terminal truncation form, KMODeltaC50) with that of the wild-type enzyme
      expressed in COS-7 cells. The second role was demonstrated with fluorescence
      microscopy by the comparison of the intracellular localization of the wild-type,
      three carboxyl-terminal truncated forms (DeltaC20, DeltaC30 and DeltaC50), C
      terminally FLAG-tagged wild-type and a mutant KMO, where two arginine residues,
      Arg461-Arg462, were replaced with Ser residues.

PMID- 20802229
TI  - Pearls of wisdom: eat, drink, have sex (using condoms), abstain from smoking and
      be merry.

PMID- 20802230
TI  - Post-partum haemorrhage and the WOMAN trial.

PMID- 20802233
TI  - Characterization of mutations in streptomycin-resistant Mycobacterium
      tuberculosis clinical isolates in the area of Barcelona.
AB  - OBJECTIVES: To determine the proportion and type of mutations in Mycobacterium
      tuberculosis isolates resistant to streptomycin, and their relationship with the
      level of resistance and with the epidemiological molecular pattern of the
      isolates. METHODS: Sixty-nine streptomycin-resistant isolates from a M.
      tuberculosis strain collection (1995-2005) from Barcelona were studied. The MIC
      of streptomycin for each isolate was determined using the proportions method with
      Middlebrook 7H11 medium. The entire rpsL gene and two specific fragments of the
      rrs gene (the 530 loop and the 912 region) were sequenced. IS6110-restriction
      fragment length polymorphism and spoligotyping were performed in each isolate.
      RESULTS: Twenty-six (26/69, 37.7%) streptomycin-resistant isolates presented a
      mutation in either the rpsL gene and/or the rrs530 loop, with no mutation in the
      rrs912 region. Seventeen (24.6%) isolates showed rpsL mutations (codons 43 and
      88) associated with high MIC levels. Nine (13.0%) isolates had alterations in the
      rrs gene (A513T, A513C and C516T). Nineteen isolates (19/64, 29.7%) were
      classified into seven clusters (containing 2-5 isolates per cluster). Nineteen
      different spoligotype patterns were found. All the LAM3 spoligotype isolates
      (10/67, 14.9%) were associated with a C491T change in the rrs gene, being also
      observed in all LAM3 streptomycin-susceptible isolates. CONCLUSIONS: Mutations in
      the rpsL and rrs genes were detected in 37.7% of streptomycin-resistant M.
      tuberculosis isolates. High-level resistance was associated with mutations in the
      rpsL gene, whereas wild-type isolates showed low MIC levels. The presence of the
      C491T substitution in the rrs gene in streptomycin-susceptible and -resistant
      isolates demonstrates that this change is an epidemiological marker associated
      with LAM3 sublineage.

PMID- 20802234
TI  - Tuning the serum persistence of human serum albumin domain III:diabody fusion
      proteins.
AB  - The long circulation persistence of human serum albumin (HSA) is enabled by its
      domain III (DIII) interaction with the neonatal Fc receptor (FcRn). A protein
      scaffold based on HSA DIII was designed. To modify the serum half life of the
      scaffold, residues H535, H510, and H464 were individually mutated to alanine. HSA
      DIII wild type (WT) and variants were fused to the anti-carcinoembryonic antigen
      (CEA) T84.66 diabody (Db), radiolabeled with (124)I and injected into xenografted
      athymic mice for serial PET/CT imaging. All proteins targeted the CEA-positive
      tumor. The mean residence times (MRT) of the proteins, calculated by quantifying
      blood activity from the PET images, were: Db-DIII WT (56.7 h), H535A (25 h),
      H510A (20 h), H464A (17 h), compared with Db (2.9 h). Biodistribution confirmed
      the order of blood clearance from slow to fast: Db-DIII WT > H535A > H510A >
      H464A > Db with 4.0, 2.0, 1.8, 1.6 and 0.08 %ID/g of remaining blood activity at
      51 h, respectively. This study demonstrates that attenuating the DIII-FcRn
      interaction provides a way of controlling the pharmacokinetics of the entire Db
      DIII fusion protein without compromising tumor targeting. H464 appears to be most
      crucial for FcRn binding (greatest reduction in MRT), followed by H510 and H535.
      By mutating the DIII scaffold, we can dial serum kinetics for imaging or therapy
      applications.

PMID- 20802235
TI  - TrkC plays an essential role in breast tumor growth and metastasis.
AB  - Tropomyosin-related kinase (Trk) C, a member of the Trk family of neurotrophin
      receptors, has been implicated in the growth and survival of human cancer
      tissues. Here, we report that TrkC is frequently overexpressed in human breast
      cancers and plays an essential role in tumor growth and metastasis. Ectopic
      expression of TrkC in non-malignant mammary epithelial cells suppressed anoikis,
      which correlated with activation of the Ras-mitogen-activated protein kinase and
      phosphatidylinositol-3-OH kinase (PI3K)/Akt pathways, and reduced expression of
      the metastatic regulator Twist. Furthermore, suppression of TrkC expression in
      highly metastatic mammary carcinoma cells inhibited their growth in vitro, as
      well as their ability to metastasize from the mammary gland to the lung in vivo.
      These results have identified TrkC as a critical regulator of breast cancer cell
      growth and metastasis.

PMID- 20802236
TI  - DNA methylation profiles delineate etiologic heterogeneity and clinically
      important subgroups of bladder cancer.
AB  - DNA methylation profiles can be used to define molecular cancer subtypes that may
      better inform disease etiology and clinical decision-making. This investigation
      aimed to create DNA methylation profiles of bladder cancer based on CpG
      methylation from almost 800 cancer-related genes and to then examine the
      relationship of those profiles with exposures related to risk and clinical
      characteristics. DNA, derived from formalin-fixed paraffin-embedded tumor samples
      obtained from incident cases involved in a population-based case-control study of
      bladder cancer in New Hampshire, was used for methylation profiling on the
      Illumina GoldenGate Methylation Bead Array. Unsupervised clustering of those loci
      with the greatest change in methylation between tumor and non-diseased tissue was
      performed to defined molecular subgroups of disease, and univariate tests of
      association followed by multinomial logistic regression was used to examine the
      association between these classes, bladder cancer risk factors and clinical
      phenotypes. Membership in the two most methylated classes was significantly
      associated with invasive disease (P < 0.001 for both class 3 and 4). Male gender
      (P = 0.04) and age >70 years (P = 0.05) was associated with membership in one of
      the most methylated classes. Finally, average water arsenic levels in the highest
      percentile predicted membership in an intermediately methylated class of tumors
      (P = 0.02 for both classes). Exposures and demographic associated with increased
      risk of bladder cancer specifically associate with particular subgroups of tumors
      defined by DNA methylation profiling and these subgroups may define more
      aggressive disease.

PMID- 20802237
TI  - Genetic variations in TERT-CLPTM1L genes and risk of squamous cell carcinoma of
      the head and neck.
AB  - Single-nucleotide polymorphisms (SNPs) of TERT-rs2736098 (C > T) and CLPTM1L
      rs401681(C > T) at the 5p15.33 locus are significantly associated with cancer
      risk as reported in genome-wide association studies (GWAS), but there are no
      reported studies for squamous cell carcinoma of the head and neck (SCCHN). In a
      case-control study of 1079 SCCHN cases and 1115 cancer-free controls of non
      Hispanic whites who were frequency matched by age and sex, we genotyped for these
      two SNPs and assessed their associations with SCCHN risk. Compared with the CC
      genotypes of each polymorphism, the associations of a slightly reduced risk of
      SCCHN with the variant genotypes of CT + TT of both polymorphisms were
      approaching statistical significance [Odds ratio (OR) = 0.90, 95% confidence
      interval (CI) = 0.76-1.08 for TERT-rs2736098 and OR = 0.86, 95% CI = 0.71-1.04
      for CLPTM1L-rs401681, respectively]. When the two SNPs were combined, the variant
      genotypes of the two SNPs were significantly associated a moderately reduced risk
      of SCCHN (OR = 0.82, 95% CI = 0.67-0.99), and the number of variant genotypes was
      associated with a significantly reduced risk in a dose-response manner (P =
      0.028). Furthermore, the reduced risk was more pronounced in ever smokers, ever
      drinkers and patients with oropharyngeal cancer. Our results suggested that these
      two SNPs at the 5p15.33 locus may be associated with a reduced risk of SCCHN,
      particularly for their combined effect. Although we added additional evidence for
      the association of the two SNPs with cancer risk as reported in GWAS, additional
      studies are needed to replicate our findings.

PMID- 20802239
TI  - Evolutionary history of chimpanzees inferred from complete mitochondrial genomes.
AB  - Investigations into the evolutionary history of the common chimpanzee, Pan
      troglodytes, have produced inconsistent results due to differences in the types
      of molecular data considered, the model assumptions employed, and the quantity
      and geographical range of samples used. We amplified and sequenced 24 complete P.
      troglodytes mitochondrial genomes from fecal samples collected at multiple study
      sites throughout sub-Saharan Africa. Using a "relaxed molecular clock," fossil
      calibrations, and 12 additional complete primate mitochondrial genomes, we
      analyzed the pattern and timing of primate diversification in a Bayesian
      framework. Our results support the recognition of four chimpanzee subspecies.
      Within P. troglodytes, we report a mean (95% highest posterior density [HPD])
      time since most recent common ancestor (tMRCA) of 1.026 (0.811-1.263) Ma for the
      four proposed subspecies, with two major lineages. One of these lineages (tMRCA =
      0.510 [0.387-0.650] Ma) contains P. t. verus (tMRCA = 0.155 [0.101-0.213] Ma) and
      P. t. ellioti (formerly P. t. vellerosus; tMRCA = 0.157 [0.102-0.215] Ma), both
      of which are monophyletic. The other major lineage contains P. t. schweinfurthii
      (tMRCA = 0.111 [0.077-0.146] Ma), a monophyletic clade nested within the P. t.
      troglodytes lineage (tMRCA = 0.380 [0.296-0.476] Ma). We utilized two analysis
      techniques that may be of widespread interest. First, we implemented a Yule
      speciation prior across the entire primate tree with separate coalescent priors
      on each of the chimpanzee subspecies. The validity of this approach was confirmed
      by estimates based on more traditional techniques. We also suggest that accurate
      tMRCA estimates from large computationally difficult sequence alignments may be
      obtained by implementing our novel method of bootstrapping smaller randomly
      subsampled alignments.

PMID- 20802238
TI  - Population genetic analysis of the uncoupling proteins supports a role for UCP3
      in human cold resistance.
AB  - Production of heat via nonshivering thermogenesis (NST) is critical for
      temperature homeostasis in mammals. Uncoupling protein UCP1 plays a central role
      in NST by uncoupling the proton gradients produced in the inner membranes of
      mitochondria to produce heat; however, the extent to which UCP1 homologues, UCP2
      and UCP3, are involved in NST is the subject of an ongoing debate. We used an
      evolutionary approach to test the hypotheses that variants that are associated
      with increased expression of these genes (UCP1 -3826A, UCP2 -866A, and UCP3 -55T)
      show evidence of adaptation with winter climate. To that end, we calculated
      correlations between allele frequencies and winter climate variables for these
      single-nucleotide polymorphisms (SNPs), which we genotyped in a panel of 52
      worldwide populations. We found significant correlations with winter climate for
      UCP1 -3826G/A and UCP3 -55C/T. Further, by analyzing previously published
      genotype data for these SNPs, we found that the peak of the correlation for the
      UCP1 region occurred at the disease-associated -3826A/G variant and that the UCP3
      region has a striking signal overall, with several individual SNPs showing
      interesting patterns, including the -55C/T variant. Resequencing of the regions
      in a set of three diverse population samples helped to clarify the signals that
      we found with the genotype data. At UCP1, the resequencing data revealed modest
      evidence that the haplotype carrying the -3826A variant was driven to high
      frequency by selection. In the UCP3 region, combining results from the climate
      analysis and resequencing survey suggest a more complex model in which variants
      on multiple haplotypes may independently be correlated with temperature. This is
      further supported by an excess of intermediate frequency variants in the UCP3
      region in the Han Chinese population. Taken together, our results suggest that
      adaptation to climate influenced the global distribution of allele frequencies in
      UCP1 and UCP3 and provide an independent source of evidence for a role in cold
      resistance for UCP3.

PMID- 20802240
TI  - The start of smoking and prior lifestyles among Japanese college students: a
      retrospective cohort study.
AB  - INTRODUCTION: Using annual health checkup questionnaire data, the present study
      aimed to explore the relationship between lifestyles and subsequent new smoking
      of college students. METHODS: Among the all undergraduate students who entered
      Kyoto University from 2000 through 2004, those who had never smoked until the
      beginning of their 2nd year were enrolled in the study. A Cox proportional
      hazards regression analysis was performed to reveal the association between
      lifestyle characteristics at the beginning of the 2nd year and the start of
      smoking during the 2nd and 3rd years. RESULTS: A total of 12,872 participants
      were enrolled in the analyses, 865 of whom started smoking during the subsequent
      2 years. Among the lifestyle characteristics we examined, skipping breakfast 2-4
      times a week (hazard ratio [HR] = 1.6; 95% CI = 1.4-1.9) or >= 5 times a week (HR
      = 2.0; 95% CI = 1.6-2.5), eating out for supper 2-4 times a week (HR = 1.4; 95%
      CI = 1.2-1.7) or >= 5 times a week (HR = 1.4; 95% CI = 1.2-1.8), drinking
      occasionally (HR = 1.7; 95% CI = 1.5-2.0) or almost everyday (HR = 4.1; 95% CI =
      3.1-5.7), and sleeping < 6 hr a day (HR = 1.3; 95% CI = 1.1-1.6) were significant
      risk factors for the start of smoking. However, exercising >= 5 times a week (HR
      = 0.5; 95% CI = 0.4-0.7) was a protective factor. DISCUSSION: Our results
      suggested that even never-smoking undergraduates with poor life habits are likely
      to start smoking and would make good candidates for preventive intervention.

PMID- 20802241
TI  - Statistical criteria for selecting the optimal number of untreated subjects
      matched to each treated subject when using many-to-one matching on the propensity
      score.
AB  - Propensity-score matching is increasingly being used to estimate the effects of
      treatments using observational data. In many-to-one (M:1) matching on the
      propensity score, M untreated subjects are matched to each treated subject using
      the propensity score. The authors used Monte Carlo simulations to examine the
      effect of the choice of M on the statistical performance of matched estimators.
      They considered matching 1-5 untreated subjects to each treated subject using
      both nearest-neighbor matching and caliper matching in 96 different scenarios.
      Increasing the number of untreated subjects matched to each treated subject
      tended to increase the bias in the estimated treatment effect; conversely,
      increasing the number of untreated subjects matched to each treated subject
      decreased the sampling variability of the estimated treatment effect. Using
      nearest-neighbor matching, the mean squared error of the estimated treatment
      effect was minimized in 67.7% of the scenarios when 1:1 matching was used. Using
      nearest-neighbor matching or caliper matching, the mean squared error was
      minimized in approximately 84% of the scenarios when, at most, 2 untreated
      subjects were matched to each treated subject. The authors recommend that, in
      most settings, researchers match either 1 or 2 untreated subjects to each treated
      subject when using propensity-score matching.

PMID- 20802242
TI  - Morphological changes and synaptogenesis of corticothalamic neurons in the
      somatosensory cortex of rat during perinatal development.
AB  - When rat fetuses grew from embryonic day (E) 18 to the day of birth (P0), the
      corticothalamic (CT) neurons, as identified by back labeling with 1,1'
      dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (DiI), in the somatosensory
      cortex underwent gradual changes in the shape of their cell bodies, in their
      distribution in the cortical plate and in the complexity of dendritic branching.
      Fluorescence immunocytochemical studies indicated that in the marginal zone (MZ)
      the apical dendrites of the CT neurons formed contacts with horizontally oriented
      axons and contained putative glutamatergic, as clusters exhibiting both
      synaptophysin and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
      receptor GluR1 subunit immunoreactivities, and gamma-aminobutyric acid (GABA)
      ergic synapses, as clusters exhibiting both synaptophysin and gephyrin
      immunoreactivities. Quantitative analyses further revealed that during this
      perinatal period, the proportion of CT neurons containing glutamatergic synapses
      increased significantly, whereas the proportion of CT neurons containing
      GABAergic synapses remained virtually unchanged. Our results indicate that
      glutamatergic and GABAergic synapses between the CT neurons and the axons in the
      MZ are already formed in rat cortices as early as E18 and further suggest that
      the activities of the neural networks in the somatosensory cortex could be
      conveyed to their targets in the thalamus in rat brains at least 3 days before
      birth.

PMID- 20802243
TI  - Implementation of the NHS Health Checks programme: baseline assessment of risk
      factor recording in an urban culturally diverse setting.
AB  - BACKGROUND: National Health Service (NHS) Health Checks, a population-wide
      prevention programme introduced during 2009, aims to measure and manage
      cardiovascular disease (CVD) risk factors among all persons aged 40-74 years in
      England. The potential workload implications of the programme for general
      practice are considerable, particularly in deprived culturally diverse settings.
      OBJECTIVE: To examine the baseline levels of CVD risk factor recording in general
      practices located in Ealing, North West London. METHODS: Cross-sectional study
      using data extracted from electronic medical records in 14 general practices
      between December 2008 and January 2009. The completeness of blood pressure,
      smoking, body mass index (BMI) and cholesterol recording was examined by practice
      and patient characteristics. RESULTS: Recording of blood pressure [85.6%
      (practice interquartile range = 10.1)] and smoking status [95.8% (2.6)] was very
      high in practices. Recording of BMI [72.8% (23.4)] and cholesterol [55.6% (25.3)]
      was considerably lower. There were large differences in recording between
      practices (range for cholesterol: 33.6-78.0%), though these were largely
      explained by patient characteristics. In regression analysis, hypertensive
      patients [adjusted odds ratio (AOR) = 36.3, 95% confidence interval (CI) 21.0
      62.9], women [AOR = 2.88 (95% CI 2.64-3.15)] and older patients [AOR = 2.75 (95%
      CI 2.28-3.32) for 65-74 against 35-44 years of age] had better recording of blood
      pressure as well as BMI and cholesterol. Recording of blood pressure [AOR = 1.38
      (95% CI 1.09-1.75)] and cholesterol [AOR = 1.47 (95% CI 1.30-1.66)] was
      significantly higher among South Asian patients. CONCLUSIONS: The workload
      implications of the NHS Health Checks programme for general practices in England
      are substantial. There are considerable variations in risk factor recording
      between practices and between age, gender and ethnic groups.

PMID- 20802246
TI  - Ticagrelor vs. clopidogrel in patients with acute coronary syndromes and
      diabetes: a substudy from the PLATelet inhibition and patient Outcomes (PLATO)
      trial.
AB  - AIMS: patients with diabetes mellitus (DM) have high platelet reactivity and are
      at increased risk of ischaemic events and bleeding post-acute coronary syndromes
      (ACS). In the PLATelet inhibition and patient Outcomes (PLATO) trial, ticagrelor
      reduced the primary composite endpoint of cardiovascular death, myocardial
      infarction, or stroke, but with similar rates of major bleeding compared with
      clopidogrel. We aimed to investigate the outcome with ticagrelor vs. clopidogrel
      in patients with DM or poor glycaemic control. METHODS AND RESULTS: we analysed
      patients with pre-existing DM (n = 4662), including 1036 patients on insulin,
      those without DM (n = 13 951), and subgroups based on admission levels of
      haemoglobin A1c (HbA1c; n = 15 150). In patients with DM, the reduction in the
      primary composite endpoint (HR: 0.88, 95% CI: 0.76-1.03), all-cause mortality
      (HR: 0.82, 95% CI: 0.66-1.01), and stent thrombosis (HR: 0.65, 95% CI: 0.36-1.17)
      with no increase in major bleeding (HR: 0.95, 95% CI: 0.81-1.12) with ticagrelor
      was consistent with the overall cohort and without significant diabetes status-by
      treatment interactions. There was no heterogeneity between patients with or
      without ongoing insulin treatment. ticagrelor reduced the primary endpoint, all
      cause mortality, and stent thrombosis in patients with HbA1c above the median
      (HR: 0.80, 95% CI: 0.70-0.91; HR: 0.78, 95% CI: 0.65-0.93; and HR: 0.62, 95% CI:
      0.39-1.00, respectively) with similar bleeding rates (HR: 0.98, 95% CI: 0.86
      1.12). CONCLUSION: ticagrelor, when compared with clopidogrel, reduced ischaemic
      events in ACS patients irrespective of diabetic status and glycaemic control,
      without an increase in major bleeding events.

PMID- 20802247
TI  - Guidelines for the management of atrial fibrillation: the Task Force for the
      Management of Atrial Fibrillation of the European Society of Cardiology (ESC).

PMID- 20802249
TI  - EPO's rescue mission in acute myocardial infarction: still more hopes than
      evidence.

PMID- 20802248
TI  - Guidelines on myocardial revascularization.

PMID- 20802250
TI  - A single dose of erythropoietin in ST-elevation myocardial infarction.
AB  - AIMS: Cardioprotective effects of erythropoietin (EPO) have been shown in
      experimental and smaller clinical studies. We performed a prospective,
      multicentre, randomized trial to assess the effects of a single high dose of EPO
      after primary coronary intervention (PCI) for an ST-elevation myocardial
      infarction (STEMI). Methods and results Patients with a successful PCI for a
      first STEMI were randomized to receive either standard medical care alone, or in
      combination with a single bolus with 60,000 IU i.v. of epoetin alfa within 3 h
      after PCI. Primary endpoint was left ventricular ejection fraction (LVEF) after 6
      weeks, assessed by planar radionuclide ventriculography. Pre-specified secondary
      endpoints included enzymatic infarct size and major adverse cardiovascular
      events. A total of 529 patients were enrolled (EPO n = 263, control n = 266). At
      baseline (before EPO administration), groups were well-matched for all relevant
      characteristics. After a mean of 6.5 (+/- 2.0) weeks, LVEF was 0.53 (+/- 0.10) in
      the EPO group and 0.52 (+/- 0.11) in the control group (P = 0.41). Median area
      under the curve (inter-quartile range) after 72 h for creatinine kinase was 50
      136 (28 212-76 664)U/L per 72 h in the EPO group and 53 510 (33 973-90 486)U/L
      per 72 h in the control group (P = 0.058). More major adverse cardiac events
      occurred in the control than in the EPO group (19 vs. 8; P = 0.032). Conclusion A
      single high dose of EPO after a successful PCI for a STEMI did not improve LVEF
      after 6 weeks. However, the use of EPO was related to less major adverse
      cardiovascular events and a favourable clinical safety profile. CLINICAL TRIAL
      REGISTRATION INFORMATION: NCT00449488;
      http://www.clinicaltrials.gov/ct2/show/NCT00449488?term=voors&rank=2.

PMID- 20802251
TI  - Model-based clustering of microarray expression data via latent Gaussian mixture
      models.
AB  - MOTIVATION: In recent years, work has been carried out on clustering gene
      expression microarray data. Some approaches are developed from an algorithmic
      viewpoint whereas others are developed via the application of mixture models. In
      this article, a family of eight mixture models which utilizes the factor analysis
      covariance structure is extended to 12 models and applied to gene expression
      microarray data. This modelling approach builds on previous work by introducing a
      modified factor analysis covariance structure, leading to a family of 12 mixture
      models, including parsimonious models. This family of models allows for the
      modelling of the correlation between gene expression levels even when the number
      of samples is small. Parameter estimation is carried out using a variant of the
      expectation-maximization algorithm and model selection is achieved using the
      Bayesian information criterion. This expanded family of Gaussian mixture models,
      known as the expanded parsimonious Gaussian mixture model (EPGMM) family, is then
      applied to two well-known gene expression data sets. RESULTS: The performance of
      the EPGMM family of models is quantified using the adjusted Rand index. This
      family of models gives very good performance, relative to existing popular
      clustering techniques, when applied to real gene expression microarray data.
      AVAILABILITY: The reduced, preprocessed data that were analysed are available at
      www.paulmcnicholas.info

PMID- 20802252
TI  - Cysteine-scanning analysis of helices TM8, TM9a, and TM9b and intervening loops
      in the YgfO xanthine permease: a carboxyl group is essential at ASP-276.
AB  - Bacterial and fungal members of the ubiquitous nucleobase-ascorbate transporter
      (NAT/NCS2) family use the NAT signature motif, a conserved 11-amino acid sequence
      between amphipathic helices TM9a and TM9b, to define function and selectivity of
      the purine binding site. To examine the role of flanking helices TM9a, TM9b, and
      TM8, we employed Cys-scanning analysis of the xanthine-specific homolog YgfO from
      Escherichia coli. Using a functional mutant devoid of Cys residues (C-less), each
      amino acid residue in sequences
      (259)FLVVGTIYLLSVLEAVGDITATAMVSRRPIQGEEYQSRLKGGVLADGLVSVIASAV(314) and
      (342)TIAVMLVILGLFP(354) including these TMs (underlined) was replaced
      individually with Cys, except the irreplaceable Glu-272 and Asp-304, which had
      been studied previously. Of 67 single Cys mutants, 55 accumulate xanthine to 35
      140% of the steady state observed with C-less, five (I265C, D276C, I277C, G299C,
      L350C) accumulate to low levels (10-20%) and seven (T278C, A279C, T280C, A281C,
      G305C, G351C, P354C) show negligible expression in the membrane. Extensive
      mutagenesis reveals that a carboxyl group is needed at Asp-276 for high activity
      and that D276E differs from wild type as it recognizes 8-methylxanthine (K(i) 79
      MUm) but fails to recognize 2-thioxanthine, 3-methylxanthine or 6-thioxanthine;
      bulky replacements of Ala-279 or Thr-280 and replacements of Gly-305, Gly-351, or
      Pro-354 impair activity or expression. Single Cys mutants V261C, A273C, G275C,
      and S284C are sensitive to inactivation by N-ethylmaleimide and sensitivity of
      G275C (IC(50) 15 MUm) is enhanced in the presence of substrate. The data suggest
      that residues crucial for the transport mechanism cluster in two conserved
      motifs, at the cytoplasmic end of TM8 (EXXGDXXAT) and in TM9a (GXXXDG).

PMID- 20802253
TI  - Glycemia determines the effect of type 2 diabetes risk genes on insulin
      secretion.
AB  - OBJECTIVE: Several single nucleotide polymorphisms (SNPs) in diabetes risk genes
      reduce glucose- and/or incretin-induced insulin secretion. Here, we investigated
      interactions between glycemia and such diabetes risk polymorphisms. RESEARCH
      DESIGN AND METHODS: Insulin secretion was assessed by insulinogenic index and
      areas under the curve of C-peptide/glucose in 1,576 subjects using an oral
      glucose tolerance test (OGTT). Participants were genotyped for 10 diabetes risk
      SNPs associated with beta-cell dysfunction: rs5215 (KCNJ11), rs13266634
      (SLC30A8), rs7754840 (CDKAL1), rs10811661 (CDKN2A/2B), rs10830963 (MTNR1B),
      rs7903146 (TCF7L2), rs10010131 (WFS1), rs7923837 (HHEX), rs151290 (KCNQ1), and
      rs4402960 (IGF2BP2). Furthermore, the impact of the interaction between genetic
      variation in TCF7L2 and glycemia on changes in insulin secretion was tested in
      315 individuals taking part in a lifestyle intervention study. RESULTS: For the
      SNPs in TCF7L2 and WFS1, we found a significant interaction between glucose
      control and insulin secretion (all P <= 0.0018 for glucose * genotype). When
      plotting insulin secretion against glucose at 120 min OGTT, the compromising SNP
      effects on insulin secretion are most apparent under high glucose. In the
      longitudinal study, rs7903146 in TCF7L2 showed a significant interaction with
      baseline glucose tolerance upon change in insulin secretion (P = 0.0027).
      Increased glucose levels at baseline predicted an increase in insulin secretion
      upon improvement of glycemia by lifestyle intervention only in carriers of the
      risk alleles. CONCLUSIONS: For the diabetes risk genes TCF7L2 and WFS1, which are
      associated with impaired incretin signaling, the level of glycemia determines SNP
      effects on insulin secretion. This indicates the increasing relevance of these
      SNPs during the progression of prediabetes stages toward clinically overt type 2
      diabetes.

PMID- 20802255
TI  - Adiponectin prevents diabetic premature senescence of endothelial progenitor
      cells and promotes endothelial repair by suppressing the p38 MAP kinase/p16INK4A
      signaling pathway.
AB  - OBJECTIVE: A reduced number of circulating endothelial progenitor cells (EPCs)
      are casually associated with the cardiovascular complication of diabetes.
      Adiponectin exerts multiple protective effects against cardiovascular disease,
      independent of its insulin-sensitizing activity. The objective of this study was
      to investigate whether adiponectin plays a role in modulating the bioavailability
      of circulating EPCs and endothelial repair. RESEARCH DESIGN AND METHODS:
      Adiponectin knockout mice were crossed with db(+/-) mice to produce db/db
      diabetic mice without adiponectin. Circulating number of EPCs were analyzed by
      flow cytometry. Reendothelialization was evaluated by staining with Evans blue
      after wire-induced carotid injury. RESULTS: In adiponectin knockout mice, the
      number of circulating EPCs decreased in an age-dependent manner compared with the
      wild-type controls, and this difference was reversed by the chronic infusion of
      recombinant adiponectin. In db/db diabetic mice, the lack of adiponectin
      aggravated the hyperglycemia-induced decrease in circulating EPCs and also
      diminished the stimulatory effects of the PPARgamma agonist rosiglitazone on EPC
      production and reendothelialization. In EPCs isolated from both human peripheral
      blood and mouse bone marrow, treatment with adiponectin prevented high glucose
      induced premature senescence. At the molecular level, adiponectin decreased high
      glucose-induced accumulation of intracellular reactive oxygen species and
      consequently suppressed activation of p38 MAP kinase (MAPK) and expression of the
      senescence marker p16(INK4A). CONCLUSIONS: Adiponectin prevents EPC senescence by
      inhibiting the ROS/p38 MAPK/p16(INK4A) signaling cascade. The protective effects
      of adiponectin against diabetes vascular complications are attributed in part to
      its ability to counteract hyperglycemia-mediated decrease in the number of
      circulating EPCs.

PMID- 20802254
TI  - Conditional gene targeting in mouse pancreatic beta-Cells: analysis of ectopic
      Cre transgene expression in the brain.
AB  - OBJECTIVE: Conditional gene targeting has been extensively used for in vivo
      analysis of gene function in beta-cell biology. The objective of this study was
      to examine whether mouse transgenic Cre lines, used to mediate beta-cell- or
      pancreas-specific recombination, also drive Cre expression in the brain. RESEARCH
      DESIGN AND METHODS: Transgenic Cre lines driven by Ins1, Ins2, and Pdx1 promoters
      were bred to R26R reporter strains. Cre activity was assessed by beta
      galactosidase or yellow fluorescent protein expression in the pancreas and the
      brain. Endogenous Pdx1 gene expression was monitored using Pdx1(tm1Cvw) lacZ
      knock-in mice. Cre expression in beta-cells and co-localization of Cre activity
      with orexin-expressing and leptin-responsive neurons within the brain was
      assessed by immunohistochemistry. RESULTS: All transgenic Cre lines examined that
      used the Ins2 promoter to drive Cre expression showed widespread Cre activity in
      the brain, whereas Cre lines that used Pdx1 promoter fragments showed more
      restricted Cre activity primarily within the hypothalamus. Immunohistochemical
      analysis of the hypothalamus from Tg(Pdx1-cre)(89.1Dam) mice revealed Cre
      activity in neurons expressing orexin and in neurons activated by leptin. Tg(Ins1
      Cre/ERT)(1Lphi) mice were the only line that lacked Cre activity in the brain.
      CONCLUSIONS: Cre-mediated gene manipulation using transgenic lines that express
      Cre under the control of the Ins2 and Pdx1 promoters are likely to alter gene
      expression in nutrient-sensing neurons. Therefore, data arising from the use of
      these transgenic Cre lines must be interpreted carefully to assess whether the
      resultant phenotype is solely attributable to alterations in the islet beta
      cells.

PMID- 20802256
TI  - Short- and long-term efficacy of combined cabergoline and octreotide treatment in
      controlling igf-I levels in acromegaly.
AB  - OBJECTIVE: Nearly 40% of acromegalic patients fail to control GH/IGF-I levels
      with somatostatin analogues (SA). Dopaminergic agonists (DA) are even less
      effective, but combination therapy with SA and DA normalizes IGF-I levels in 33
      56% of patients not controlled by octreotide alone in short-term studies. This
      study was designed to evaluate short- and long-term efficacy of cabergoline in
      controlling IGF-I levels in acromegalic patients receiving octreotide. DESIGN:
      Open-label, single arm, prospective trial. Nineteen patients (14 females, 29-78
      years of age) with high IGF-I on octreotide-LAR (30 mg/month IM) for > or =6
      months were enrolled. Study I: Cabergoline (PO) was started at 1.0, increased to
      2.0 and 3.5 mg/week, and withdrawn at 6-week intervals. IGF-I, GH, and PRL were
      measured at baseline and at 6-week intervals. Study II: Responder patients (IGF-I
      < or =1 ULN) resumed cabergoline at individual lowest effective doses and were
      evaluated at 6-month intervals for > or =12 months. Study III: Responders were
      withdrawn from octreotide and hormonally evaluated at 3-month intervals. METHODS:
      Serum IGF-I (IRMA), GH (ICMA) and PRL (ICMA) levels were determined by
      commercially available kits. RESULTS: Addition of cabergoline to octreotide-LAR
      normalized IGF-I levels in 7 of 19 patients (37%) during both short- and long
      term follow-up (12-27 months, mean: 18 months). Octreotide withdrawal increased
      IGF-I levels in only 2 of 6 responder patients. Normalization of IGF-I levels by
      cabergoline was strongly associated with IGF-I < or =2.2 ULNR and/or GH < or =4.0
      ng/ml under octreotide treatment. CONCLUSION: Addition of cabergoline to
      octreotide was effective in both short- and long-term control of IGF-I in
      acromegaly, especially in patients with mild/moderately elevated GH/IGF-I levels
      during octreotide.

PMID- 20802257
TI  - The effect of Ginkgo biloba extract (EGb 761) on parameters of oxidative stress
      in different regions of aging rat brains after acute hypoxia.
AB  - BACKGROUND AND AIMS: Neurodegenerative processes of aging seem to be associated
      with oxidative stress by reactive oxygen species (ROS). This study investigates
      the influence of age and of acute respiratoric hypoxia on parameters of oxidative
      stress in different brain regions of Wistar rats and the protective effects of
      Ginkgo extract (EGb 761) as a radical scavenger. METHODS: Biopsies of frontal and
      temporal cortices, the cerebellum, and the brainstem of young and old rats (each
      group n=6-8: normoxic - hypoxic; unprotected - EGb-protected) were analyzed for
      malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, glutathione
      (GSH) content, and creatine kinase (CK) activity. Experimental hypoxia:
      downregulation of oxygen partial pressure to 5 vol. % for 20 minutes. EGb
      administration: daily 100 mg/kg of body weight in drinking water for 3 months.
      RESULTS: Effects of age: While most oxidative stress parameters in the temporal
      cortex, the cerebellum, and the brainstem are increased, this is not the case in
      the frontal cortex; after additional hypoxia SOD and GSH are diminished in the
      temporal cortex and the brainstem of old rats. EGb treatment causes contradictory
      alterations in young, old, and hypoxic brain regions. Minor effects are seen in
      old hypoxic brains, while there are some protective effects in old normoxic
      brainstems and cerebellums. CONCLUSIONS: The old brain appears to adapt
      appropriately to chronic oxidative stress and to the specific conditions of
      shortterm hypoxia. EGb's protective effect is especially notable in the brainstem
      and the cerebellum.

PMID- 20802258
TI  - Benefits of home-based rocking-chair exercise for physical performance in
      community-dwelling elderly women: a randomized controlled trial.
AB  - BACKGROUND AND AIMS: Home-based exercise is a viable alternative for older adults
      with difficulties in exercise opportunities outside the home. The aim of this
      study was to investigate the benefits of home-based rocking-chair training, and
      its effects on the physical performance of elderly women. METHODS: Community-
      dwelling women (n=51) aged 73-87 years were randomly assigned to the rocking
      chair group (RCG, n=26) or control group (CG, n=25) by drawing lots. Baseline and
      outcome measurements were hand grip strength, maximal isometric knee extension,
      maximal walking speed over 10 meters, rising from a chair five times, and the
      Berg Balance Scale (BBS). The RCG carried out a six-week rocking-chair training
      program at home, involving ten sessions per week, twice a day for 15 minutes per
      session, and ten different movements. The CG continued their usual daily lives.
      After three months, the RCG responded to a mail questionnaire. RESULTS: After the
      intervention, the RCG improved and the CG declined. The data showed significant
      interactions of group by time in the BBS score (p=0.001), maximal knee extension
      strength (p=0.006) and maximal walking speed (p=0.046), which indicates that the
      change between groups during the follow-up period was significant. Adherence to
      the training protocol was high (96%). After three months, the exercise program
      had become a regular home exercise habit for 88.5% of the subjects. CONCLUSIONS:
      Results indicate that home-based elderly women benefit from this easily
      implemented rocking-chair exercise program. The subjects became motivated to
      participate in training and continued the exercises. This is a promising
      alternative exercise method for maintaining physical activity and leads to
      improvements in physical performance.

PMID- 20802259
TI  - A three-group comparison of acute-onset dizzy, long-term dizzy and non-dizzy
      older patients in primary care.
AB  - BACKGROUND AND AIMS: The hypothesis of increased cardiovascular risk contributing
      to chronic dizziness has been discussed controversially so far. We investigated
      older patients suffering from acute (<6 months), chronic (>= 6 months) or no
      dizziness, in terms of their cardiovascular risk and other impairments. METHODS:
      A cross-sectional three-group comparison of 257 patients (65+) presenting at
      family medicine surgeries in Germany was performed. Measures of cardiovascular
      risk, including overall scores, scores of quality of life (SF-12), activities of
      daily living (ADL), depression (GDS), dizziness handicap (DHI) and patients'
      needs (DiNA), as well as comorbidity and medication, were compared in univariate
      and multivariate logistic regression analysis. RESULTS: In univariate analysis,
      systolic and diastolic blood pressure were significantly lower in the dizziness
      groups. The overall cardiovascular risk was not increased in dizzy patients.
      Anxiety was strongly associated with dizziness, whereas other associations were
      of marginal importance. In multivariate analysis, age (OR 1.10, 95% CI 1.03
      1.17), female gender (OR 2.07, 95% CI 1.01-4.26) and anxiety (OR 2.50, 95% CI
      1.03-6.05) were associated with acute dizziness, whereas only female gender was
      significant in chronic dizziness (OR 1.96, 95% CI 1.02- 3.75). Comparing all
      dizzy patients with the non-dizzy group, lower systolic blood pressure was also
      significantly associated with dizziness. CONCLUSIONS: Results from our sample
      suggest that low systolic blood pressure is more important for dizziness in older
      patients than increased cardiovascular risk. Acute-onset and long-term dizzy
      patients were comparable in many aspects, which makes this classification less
      clinically important.

PMID- 20802260
TI  - Recruitment and retention: challenges and opportunities for the NIA funded
      Alzheimer Disease Centers Program. Introduction.

PMID- 20802262
TI  - Performance achievement award program for Get With The Guidelines--Coronary
      Artery Disease is associated with global and sustained improvement in cardiac
      care for patients hospitalized with an acute myocardial infarction.
AB  - BACKGROUND: Adherence to evidence-based guidelines for the treatment of coronary
      artery disease (CAD) is suboptimal. Our goal was to determine whether the
      performance achievement award program for Get With The Guidelines-Coronary Artery
      Disease (GWTG-CAD) was associated with global and sustained adherence to evidence
      based guidelines for acute myocardial infarction. METHODS: Adherence to evidence
      based guidelines was assessed in 170,061 hospitalized acute myocardial infarction
      patients from 418 US hospitals participating in GWTG-CAD from 2000 to 2008.
      Hospitals that received a performance achievement award by attaining 85%
      adherence with 6 GWTG performance measures for at least 12 consecutive months
      were compared with those that had enrolled in the GWTG-CAD and had not attained
      this level of adherence. The outcome measures were change in adherence for 6 GWTG
      performance measures, 9 GWTG quality measures, a composite score, and an all-or
      none measure. Generalized estimating equations were used to provide valid
      inference accounting for the within site correlation. RESULTS: Hospitals that
      maintained 85% adherence with GWTG performance measures for at least 12
      consecutive months had a higher composite score (94.78 +/- 15.99% vs. 89.72 +/-
      21.37, P < 0.0001) and an all-or-none measure (87.17% vs. 75.15%, P < 0.0001)
      compared with hospitals that had not yet attained this level of adherence.
      Hospital adherence with performance and quality measures generally improved over
      time. CONCLUSIONS: In conclusion, the performance achievement award program for
      GWTG-CAD was associated with global and sustained adherence to evidence-based
      guidelines. Our data suggest that this tool is a useful component of a quality
      improvement initiative and should be considered for other similar programs.

PMID- 20802263
TI  - "Call 911" STEMI protocol to reduce delays in transfer of patients from non
      primary percutaneous coronary intervention referral Centers.
AB  - Primary percutaneous coronary intervention (PPCI) is the preferred method of
      reperfusion for ST-segment elevation myocardial infarction (STEMI), if it can be
      performed in a timely manner by an experienced interventional cardiologist at a
      high volume STEMI Receiving Center. However, an estimated 50% of STEMI patients
      present to STEMI Referral Centers without PPCI capability. Transfer of STEMI
      patients for PPCI has been shown to improve outcomes as compared with
      fibrinolysis given at the presenting hospital. Nonetheless, transfer of STEMI
      patients for PPCI has not been used extensively in the United States and is
      associated with markedly prolonged transfer times. This study demonstrates that
      rapid transfer of STEMI patients from community hospitals without PPCI capability
      to a STEMI Receiving Center is both safe and feasible using a standardized
      protocol with an integrated transfer system.

PMID- 20802264
TI  - Prior cardiovascular interventions are not associated with worsened clinical
      outcomes in patients with symptomatic atherothrombosis.
AB  - To assess the effect of prior cardiovascular interventions on long-term clinical
      outcomes in patients with symptomatic atherothrombosis, the risk factor profiles,
      treatment patterns, and 24-month outcomes of patients in the United States with
      and without prior cardiovascular intervention (catheter-based, surgical, or lower
      limb amputation) enrolled in the global REACH (REduction of Atherothrombosis for
      Continued Health) Registry were compared. Of the 17,521 US outpatients aged > or
      =45 years with established coronary artery disease, cerebrovascular disease, or
      peripheral artery disease enrolled in the REACH Registry between December 1, 2003
      and June 1, 2004 who had > or =1 follow-up visit, 11,925 (68.1%) had a previous
      cardiovascular intervention. Prior intervention was most common in patients with
      coronary artery disease (76.7%) and least common in patients with cerebrovascular
      disease (14.6%) at baseline. Patients with prior cardiovascular intervention were
      significantly more likely to be taking antihypertensive, antithrombotic, or lipid
      lowering therapies than those without prior intervention (P < 0.0001 for each
      therapy). However, 24-month Kaplan-Meier event rates for the composite outcome of
      cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke were
      similar between patients with and without prior intervention (9.10% vs. 9.00%; P
      = 0.49). Thus, in the US REACH Registry, prior cardiovascular intervention was
      not associated with an increased risk of subsequent cardiovascular ischemic
      events during follow-up. Patients without prior cardiovascular intervention had a
      lower intensity of risk factor modification at baseline and appear to represent
      an at-risk, undertreated population.

PMID- 20802265
TI  - Perspectives on the 2009 focused updates on the management of ST-segment
      elevation myocardial infarction and percutaneous intervention.
AB  - The American College of Cardiology, American Heart Association and Society of
      Angiography and Intervention recently published updated guidelines for management
      of patients with acute ST elevation myocardial infarction (STEMI) and
      percutaneous coronary intervention (PCI). In this article, we highlight the most
      important new recommendations and review the supporting data. Key aspects of
      these updates include guidance regarding the selection of antithrombotic therapy,
      caution in treating hyperglycemia with insulin, and opinion that insufficient
      data currently exist to recommend against concomitant administration of proton
      pump inhibitors and thienopyridines. New interventional recommendations include
      support for aspiration thrombectomy, drug eluting stents, PCI of unprotected left
      main disease, and use of fractional flow reserve to guide whether PCI is
      warranted in symptomatic patients with intermediate coronary stenoses. As these
      guidelines represent a synopsis of the most recently available data in the
      management of patients with STEMI, health care providers should familiarize
      themselves with these updated recommendations to ensure optimal treatment of
      their patients.

PMID- 20802267
TI  - Evaluation of a clinical decision support system for glucose control: impact of
      protocol modifications on compliance and achievement of glycemic targets.
AB  - Treating hyperglycemia may improve patient outcome, but is a clinical challenge.
      Three variations of a computerized insulin protocol were compared with regard to
      protocol compliance and achievement of glucose target levels. In group 1, the
      existing protocol was applied, in group 2 the protocol was modified to account
      for decreasing glucose values; group 3 had a higher threshold for initiating
      insulin, wider glucose target ranges, and included instructions to regulate
      glucose around mealtimes. From July 28, 2008 until February 1, 2010, data from
      1255 patients admitted to our Intensive Cardiac Care Unit with at least 2 glucose
      measurements were analyzed. Mean age was 64 +/- 15 years, 66% were male, 21% had
      diabetes. Groups 1 to 3 included 269, 814, and 142 patients, respectively.
      Protocol compliance in group 2 was lower with 44% of the glucose measurements
      performed on time versus 51% in group 1 (P < 0.001), and insulin was dosed
      correctly in 57% versus 67% (P < 0.001). In group 3, compliance increased, 52% of
      the measurements were done on time, and insulin was dosed correctly in 71%.
      Average glucose levels increased in group 3 due to a higher threshold for
      starting insulin and a wider target range: 70% (group 1), 66% (group 2), and 61%
      (group 3) had an average glucose of <8 mmol/L (P < 0.001). Also, we observed a
      decreasing trend in incidence of hypoglycemia and reporting of noncompliance.
      Further improvements in glucose measurement technology and protocols are needed
      to optimally treat hyperglycemia in the Intensive Cardiac Care Unit.

PMID- 20802268
TI  - Utility of daily diuretic orders for identifying acute decompensated heart
      failure patients for quality improvement.
AB  - INTRODUCTION: Many studies have demonstrated gaps in adherence to American
      College of Cardiology (ACC)/American Heart Association (AHA) guidelines among
      patients with acute decompensated heart failure (ADHF). Quality improvement
      initiatives can improve compliance with guideline-recommended therapy yet a major
      challenge to such programs is identifying heart failure patients across the many
      wards and services of the complex hospital environment. METHODS AND RESULTS:
      Using our hospital's electronic order-entry system, we generated a daily list of
      all hospitalized patients receiving a loop diuretic. Over a 3-month period, each
      patient on this list was screened through chart review for a diagnosis of ADHF.
      For those patients with ADHF, a clinical reminder about ACC/AHA recommended
      therapies was placed in the chart. Patient outcomes were followed using the Get
      With The Guidelines heart failure database.During the study period, 98.6% of
      patients with ADHF were identified by the diuretics list. The diuretics list had
      a sensitivity of 98.6% and specificity of 92.2%. The diuretic list captured more
      ADHF patients than alternative methods such as chest x-ray and brain natriuretic
      peptide level. Use of the daily diuretic list and targeted reminders to
      clinicians was associated with an improvement in recommended therapies including
      smoking-cessation education and heart failure teaching. CONCLUSIONS: A daily list
      of inpatients receiving diuretics allowed real-time identification of most
      hospitalized heart failure patients at our institution. Targeted reminders to
      clinicians regarding ACC/AHA-recommended therapies for heart failure were
      associated with improvements in guideline adherence.

PMID- 20802269
TI  - Using waist circumference to screen for metabolic syndrome in an inpatient
      population.
AB  - OBJECTIVE: Metabolic syndrome (MetS) involves a combination of factors that
      increases the risk of cardiovascular disease. With no immediate physical symptoms
      or medical problems associated with this disorder, the diagnosis of MetS is a
      challenging one. The most widely recognized metabolic criteria (lipid profile,
      blood pressure, and glucose level) are commonly performed during a
      hospitalization. The waist circumference (WC) measurement, not a routine
      component of admission, is not available. Incomplete criteria affect the ability
      to diagnose MetS and prescribe risk reduction therapy. This study evaluated the
      efficacy of incorporating WC measurements in screening inpatients for MetS.
      METHODS: Over a 3-month period, 516 adult patients were admitted to medical units
      at Advocate Lutheran General Hospital in Illinois. A total of 439 (207 men and
      232 women) patients were included in this study. Nursing staff measured WC on
      admission. Additional data elements collected included fasting lipids, fasting
      plasma glucose, and early morning blood pressures. The prevalence of MetS was
      calculated using the American Heart Association criteria. RESULTS: Eliminating
      high-risk populations from the total sample, 210 (96 men and 124 women) patients
      remained in the study (refined study population). Of the 210 patients, 78% had an
      abnormal WC and the prevalence of MetS was found in 158 (75.2%). In men, the
      prevalence of MetS was 71%, and in women, 78.9%. Only 9 patients did not have an
      abnormal WC by American Heart Association definition. CONCLUSION: Measuring WC in
      the inpatient population improves the positive predictive value of the MetS
      diagnostic criteria. The measurement is an easy, inexpensive task to complete,
      providing complete criteria so that an accurate assessment can be made. Once
      identified, management of this high-risk group can focus on secondary risk
      reduction strategies.

PMID- 20802270
TI  - Office-based global cardiometabolic risk assessment: a simple tool incorporating
      nontraditional markers.
AB  - To facilitate comprehensive cardiometabolic risk assessment, we developed a
      simple 12-point checklist of traditional and emerging risk factors. We recently
      analyzed data from the Pravastatin or Atorvastatin Evaluation and Infection
      Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) trial of 4162
      high-risk patients hospitalized with recent acute coronary syndrome, and found
      that an increasing cardiometabolic risk factor count was associated with
      increasing risk of cardiovascular events over the next 2 years. In addition, we
      observed that the average number of risk factors a given patient had was 5, with
      some risk factors like obesity having clustering of additional risk factors,
      suggesting the need to assess the full list of risk factors to be able to provide
      comprehensive risk factor assessment and modification. We now have developed a 1
      page patient encounter sheet to facilitate rapid assessment of these 12
      cardiometabolic risk factors in a busy clinical office setting. It is hoped that
      with the simple risk assessment tool provided, clinicians would be able to
      comprehensively screen for and treat these traditional and nontraditional risk
      markers. As such, this could motivate both patients and physicians to work
      jointly toward reducing global cardiometabolic risk.

PMID- 20802266
TI  - Clinical pathways for acute coronary syndromes in China: protocol for a hospital
      quality improvement initiative.
AB  - Clinical pathways have been shown to be effective in improving quality of care
      for patients admitted to hospital for acute coronary syndromes (ACS) in high
      income countries. However, their utility has not formally been evaluated in low-
      or middle-income countries. The Clinical Pathways for Acute Coronary Syndromes in
      China program is a 7-year study with the overall goal of reducing evidence
      practice gaps in the management of patients admitted to hospitals in China with
      suspected ACS. The program comprises 2 phases: a prospective survey of current
      management of ACS patients to identify the areas that evidence-based patient care
      can be potentially improved, and a quality care initiative to maximize the use of
      evidence-based investigations and treatments for ACS patients in China. In this
      article, we outline the details of the study protocol, including key aspects of
      the development, implementation, and evaluation of the quality improvement
      initiative (clinical pathway) for management of patients with suspected ACS.

PMID- 20802271
TI  - Serum ferritin is linked with aortic stiffness in apparently healthy Korean
      women.
AB  - BACKGROUND: There has been strong recent interest in the association between
      serum ferritin concentrations and increased risk of cardiovascular events.
      Surplus nutrition and convenience-seeking behavior has contributed to emergence
      of an increasingly obese population, with a concurrent increase in the prevalence
      of cardiovascular diseases. To date, few studies have specifically examined the
      association between serum ferritin and aortic stiffness in healthy populations,
      thus we investigated the association between serum ferritin and aortic stiffness
      according to sex and obesity in healthy subjects. METHODS AND RESULTS: From a
      register of 196 healthy subjects (146 males, 50 females) 23 to 76 years of age,
      we measured BMI, serum ferritin, blood pressures, metabolic variables, and
      brachial ankle pulse wave velocity (baPWV). The average baPWV, serum ferritin and
      the sociodemographic prevalence (smoking, alcohol, and exercise) were higher in
      men than women. There was a positive association between serum ferritin and baPWV
      (R = 0.02) in total subjects after adjusting for age, sex, and blood pressures.
      The association between serum ferritin and baPWV (R = 0.099) in women was
      positive, yet negative in men (R = -0.007). The average baPWV and serum ferritin
      were highest in obese men, on the other hand lowest in nonobese women among 4
      groups according to sex and obesity. CONCLUSIONS: In conclusion, there was a
      stronger association between serum ferritin and PWV in healthy Korean women than
      men. Our finding suggests that cardiovascular risk factor monitoring through
      baPWV should be considered for even apparently healthy Korean women.

PMID- 20802272
TI  - Chest pain in the emergency room: a multicenter validation of the HEART Score.
AB  - OBJECTIVE: Decision-making in chest pain patients is hampered by poor diagnostic
      power of patient's history, electrocardiogram, age, risk factors, and troponin.
      Each of these findings may be qualified with 0, 1, or 2 points. Together they
      compose the HEART score. We tested the hypothesis that the HEART score predicts
      major adverse cardiac events. DESIGN: Retrospective multicenter analysis in
      patients presenting at the cardiology emergency room. SETTING: Patient inclusion
      between January 1 and March 31, 2006. PATIENTS: A total of 2161 patients were
      admitted, of which 910 patients (42%) presented with chest pain. Analysis was
      performed in 880 cases (96.7%). MAIN OUTCOME MEASURES: The primary endpoint was a
      composite of acute myocardial infarction, percutaneous coronary intervention,
      coronary artery bypass graft surgery and death, within 6 weeks after
      presentation, together called major adverse cardiac events. RESULTS: A total of
      158 patients (17.95%) reached the primary endpoint. Ninety-two patients had an
      acute myocardial infarction (10.45%), 82 a percutaneous coronary intervention
      (9.32%), 36 a coronary artery bypass graft (4.09%), and 13 died (1.48%). Of 303
      patients with HEART score 0 to 3, three (0.99%) had an endpoint. In 413 patients
      with HEART score 4 to 6, 48 cases (11.6%) reached an endpoint. In case of a HEART
      score of 7 to 10, an endpoint was reached in 107/164 cases (65.2%). CONCLUSIONS:
      The HEART score helps in making accurate diagnostic and therapeutic decisions
      without the use of radiation or invasive procedures. The HEART score is an easy,
      quick, and reliable predictor of outcome in chest pain patients and can be used
      for triage.

PMID- 20802273
TI  - Low-risk young adult patients with chest pain may not benefit from routine
      cardiac stress testing: a Bayesian analysis.
AB  - INTRODUCTION: Low-risk emergency department (ED) chest pain patients with a
      nondiagnostic electrocardiogram (ECG) and negative cardiac biomarkers are
      commonly evaluated with cardiac stress testing to detect undiagnosed coronary
      artery disease. Provocative testing incurs certain costs and may require
      additional time investment either in the ED or in an observation setting. Recent
      research has questioned the utility of provocative testing in young adults with
      negative cardiac biomarkers and nondiagnostic ECG. We sought to evaluate the
      utility of cardiac stress testing in our population of young adult patients with
      chest pain. METHODS: We performed a retrospective chart review of all chest pain
      patients aged 40 years and younger who were admitted to our ED observation unit
      over the 14-month period between April 2006 and May 2007. We included all
      patients who were admitted to the observation unit for serial biomarkers and
      provocative testing and had normal or nondiagnostic ECG, no history of coronary
      disease, and an initial negative troponin. We recorded baseline characteristics
      and stress test results of these patients and reviewed the patient charts for the
      30-day period following discharge to identify repeat hospital visits and adverse
      events. We used Bayesian analysis to estimate the rate of true-positive stress
      testing in this population, using the only prior study of unit patients showing
      as high as 2 of 220 patients testing positive as a prior estimate. RESULTS: A
      total of 36 patients met inclusion criteria; average age was 34.6 years old
      (range: 22-40 years) and 61% were male. Patient risk factors included
      hypertension (19%), diabetes (6%), family history (42%), and smoking (44%). All
      patients had negative serial cardiac biomarkers and a negative treadmill stress
      echocardiogram. Thirty-day follow-up demonstrated no adverse cardiac events. We
      performed Bayesian analysis through the addition of the 36 patients to the 220
      patients represented by prior data. The posterior probability distribution
      changed slightly in location and scale gave a median estimated rate of positive
      stress testing in this population of 1.04% (95% credible interval, 0.24%-2.78%).
      CONCLUSIONS: The population of chest pain patients younger than 40 years with no
      history of coronary disease, a nondiagnostic ECG, and negative serial biomarkers
      may not benefit from provocative testing. Our findings complement those reported
      previously on the limited utility of cardiac stress testing in this population.

PMID- 20802274
TI  - Society of Chest Pain Centers early heart attack care: an open letter.

PMID- 20802275
TI  - Recognizing and managing complications to prevent maternal deaths.

PMID- 20802276
TI  - Contributing factors associated with impulsivity-related falls in hospitalized,
      older adults.
AB  - Impulsivity-related falls (IRFs) sustained by hospitalized, older adults can lead
      to critical adverse events. The purpose of this study was to determine whether 7
      common fall risk factors contributed to the occurrence of IRF in hospitalized,
      older adults. This study found that 31% of falls were classified as IRF. Logistic
      regression indicated that inattention and mobility were contributors to IRF.
      Early identification of these 2 risk factors could improve identification of
      potential IRFs and reduce fall rates.

PMID- 20802277
TI  - Designing nursing excellence through a National Quality Forum nurse scholar
      program.
AB  - Closing the knowledge gap for current practicing nurses in the Institute of
      Medicine (IOM) core competencies is critical to providing safe patient care. The
      National Quality Forum (NQF) nurse scholar program is one organization's journey
      to close the gap in the IOM core competencies in a large teaching organization.
      The NQF nurse scholar program is positioned to provide a plan to assist current
      nurses to accelerate their learning about quality improvement, evidence-based
      practice, and informatics, 3 of the core competencies identified by the IOM, and
      focus on application of skills to NQF nurse-sensitive measures. Curriculum
      outline, educational methodologies, administrative processes, and aims of the
      project are discussed.

PMID- 20802278
TI  - Post-fall decision tree development and implementation.
AB  - Care and evaluation after a patient's fall require a number of steps to ensure
      that appropriate care is given and injury is minimized. Astute and appropriate
      assessment skills with strategic interventions and communication can minimize the
      harm from a fall. Post-Fall Decision Guidelines were developed to guide care and
      treatment and to identify potential complications after a patient has fallen.
      This systematic approach mobilizes the steps of communication, using the
      Situation-Background-Assessment-Recommendation (SBAR) format, and guides
      assessment interventions.

PMID- 20802279
TI  - The need for risk profiling in patient safety.

PMID- 20802280
TI  - A multicenter trial of aviation-style training for surgical teams.
AB  - AIMS: This study measured the effect of aviation-style team training on 3
      surgical teams from different specialties. It focused on team working and
      communication, particularly briefing, time-out, and debriefing, and sought to
      understand how improvements in team skills could be implemented in a broad range
      of naturalistic surgical environments to improve safety, quality, and efficiency.
      METHOD: Surgical teams performing maxillofacial, vascular, and neurosurgery were
      studied during 112 operations: 51 before and 61 after intervention. Human factors
      experts delivered the training of up to 2 days in the classroom followed by 6
      days of coaching in theater for each team. Trained observers measured teamwork
      using the Oxford NOTECHS and the frequency of preoperative briefings, pre
      incision time-outs, and postoperative debriefings. The Safety Attitudes
      Questionnaire and ethnographic observations were used to provide contextual
      details. RESULTS: There were significantly more time-outs (chi = 18.17, P <
      0.001), briefings (chi = 8.62, P = 0.004), and debriefings (chi = 8.58, P =
      0.004) after the intervention. The NOTECHS scores showed an interaction between
      site and intervention (F2,106 = 7.57, P = 0.001). The Safety Attitudes
      Questionnaire and ethnographic observations helped understand these differences.
      CONCLUSIONS: Aviation-style teamwork training can increase compliance and team
      performance, but this was influenced by the attitude and collaboration of key
      individuals, and the effect was reduced by significant latent failures. This
      study demonstrates the need to improve organizational and personal management
      factors in the National Health Service if training in patient safety is to be
      effective and sustained. It also shows the influence of working conditions on
      clinical studies of quality improvement.

PMID- 20802281
TI  - Activity profile and physiological requirements of junior elite basketball
      players in relation to aerobic-anaerobic fitness.
AB  - The aim of this research was to examine the demands of competitive basketball
      games and to study the relationship between athletes' physical capability and
      game performance. Physical and physiological game demands and the association of
      relevant field test with game performance were examined in 18 male junior
      basketball players. Computerized time-motion analysis, heart rate (HR), and blood
      lactate concentration [BL] measurements were performed during 6 basketball games.
      Players were also measured for explosive power, speed, agility, and maximal
      strength and endurance performance. During the games, players covered 7,558 +/-
      575 m, of which 1,743 +/- 317; 1,619 +/- 280; and 2,477 +/- 339 m were performed
      at high, moderate, and low intensities, respectively. The 19.3 +/- 3.5 and 56.0
      +/- 6.3% of the playing time was spent above 95% and at 85-95% of maximal HR,
      respectively. Average and mean peak [BL] were 5.75 +/- 1.25 and 6.22 +/- 1.34
      mmolxL, respectively. Distances covered at maximal- and high-speed running
      significantly (p < 0.01) decreased during the second half. Game maximal- and high
      speed running were significantly correlated with endurance performance (r = 0.52,
      p < 0.05 and r = 0.49, p < 0.05, respectively). High-intensity shuffling distance
      resulted in being negatively related with agility (r = -0.68, p < 0.05). This
      study showed that basketball players experience fatigue as game time progresses
      and suggests the potential benefit of aerobic and agility conditioning in junior
      basketball.

PMID- 20802282
TI  - A comparison of techniques for estimating training-induced changes in muscle
      cross-sectional area.
AB  - The ability to accurately estimate changes in muscle cross-sectional area (CSA)
      could be a useful tool for strength and conditioning practitioners to assess the
      effectiveness of a resistance training program. The purpose of this study was
      twofold: (a) to compare the reliability of 2 separate anthropometric-based field
      estimations of thigh muscle CSA with that of a more accurate, sophisticated
      imaging technique (peripheral quantitative computed tomography [pQCT] scanner)
      and (b) to determine if the field methods would be sensitive enough to detect
      changes in CSA during a resistance training program. Twenty-five healthy,
      untrained men completed 8 weeks of resistance training. Cross-sectional area
      testing occurred twice before the start of training, for reliability and again
      every 2 weeks during the study. Testing consisted of a pQCT scan of the right
      thigh followed by circumference and skinfold measurements. Two separate equations
      (Moritani and deVries [M + D] and Housh multiple regression [HMR]) were used to
      estimate CSA from the anthropometric data. The M + D and HMR methods demonstrated
      intraclass correlations of 0.983 and 0.961, respectively, but both significantly
      underestimated thigh muscle CSA when compared to the pQCT. This error was
      consistent, however, and consequently, the field methods were able to demonstrate
      increases in muscle CSA with a pattern similar to those from the pQCT. Thus,
      these equations can be useful tools to evaluate an athlete's progress toward the
      goal of increasing muscle CSA. It is the authors' hope that the present study
      will increase awareness among practitioners of these useful field methods for
      estimating training-induced changes in muscle CSA.

PMID- 20802283
TI  - Kinematic motion of the windmill softball pitch in prepubescent and pubescent
      girls.
AB  - This study examined the joint motions and movement patterns of the kinetic chain
      in the ballistic skill of performing the windmill pitch. Seventeen healthy girls
      who were currently playing competitive fast-pitch softball volunteered for the
      study. Subjects were instructed to perform 5 successful fastball windmill style
      deliveries. We selected 1 pitch for analysis based on the velocity, accuracy, and
      subjects' input. Kwon3D motion analysis package (Visol., Inc., Seoul, Korea),
      with 6 digital camcorders placed at 60 degrees apart was used for analysis. Raw
      data were interpolated using a frequency of 60 Hz and then smoothed using
      Butterworth low-pass second-order filter with a fixed cut-off frequency of 6 Hz.
      The subjects were divided into groups based on skill level: novice, intermediate,
      and advanced. Sequential progression of kinematic variables that resulted in
      increased throwing velocity and the contribution each segment (upper arm,
      forearm, and hand) possessed toward ball velocity with descriptive statistics and
      path analysis were assessed. There was evidence of sequentiality among the arm
      segments in the intermediate and advanced groups. The patterns of the shared
      positive contributions made by each of the limb segments were similar among the 3
      groups of participants. The novice group tended to rely on more of the upper arm
      and forearm than the other 2 groups. From this study, it is evident that all
      emphasis should not be placed on the shoulder, but training and conditioning
      methods should focus on the entire kinetic chain including the torso and the full
      arm segment, not just the shoulder in an attempt to gain the greatest velocity
      while performing the 360 degrees arc of the windmill softball pitch.

PMID- 20802284
TI  - A new individual and specific test to determine the aerobic-anaerobic transition
      zone (Santos Test) in competitive judokas.
AB  - The main goal of this research project was to design a specific, simple, and
      noninvasive field test to determine the individual aerobic-anaerobic transition
      zone in judokas. Our aim was to develop a field test as close as possible to real
      judo combat. Eight state- and national-level judokas participated in the study.
      To find the reliability of our test, all subjects repeated the same test under
      the same conditions within a 7-day period. Because the results were positive, we
      tested the validity of our proposal using a laboratory test that possessed the
      same characteristics. On both tests, the same parameters were studied. The mean
      data obtained in the laboratory test were as follows: maximum heart rate (HRmax):
      198.2 +/- 3.9 bxmin-1, HR at the anaerobic threshold: 170.3 +/- 5.7 bxmin-1,
      percentage of HRmax at which the anaerobic threshold appears: 85.9 +/- 2.9%,
      lactate max: 14.6 +/- 1.4 mmolxL-1, lactate threshold: 4 +/- 0.3 mmolxL-1, and
      VO2max: 58.3 +/- 4.4 mlxkgxmin-1. The mean data obtained in the field test were
      as follows: HRmax: 199.7 +/- 1.8 bxmin-1, HR at the anaerobic threshold: 169.7 +/
      2.7 bxmin-1, percentage of HRmax at which the anaerobic threshold appears: 85.0
      +/- 1.8%, lactate max: 17.0 +/- 2 mmolxL-1, lactate threshold: 4.0 +/- 0.3 mmolxL
      1, and VO2max: 59.8 +/- 3.6 mlxkgxmin-1. There were no significant differences
      between the data obtained on both tests in any of the parameters evaluated,
      except for the lactate maximum. Therefore, we can conclude that our field test is
      a useful tool for judo training.

PMID- 20802285
TI  - The effect of ankle bracing on peak mediolateral ground reaction force during
      cutting maneuvers in collegiate male basketball players.
AB  - The literature suggests that one-third of ankle injuries sustained during a
      collegiate basketball season are due to the poor execution of dynamic cutting
      movements, leading to increased mediolateral force being placed on the unstable
      ankle. The objective of the present study was to examine the effect of ankle
      bracing on peak mediolateral ground reaction forces (PMGRF) during sidestep
      cutting motions in collegiate basketball players. Ten male collegiate basketball
      players, with no previous history of ankle trauma, performed sidestep cutting
      motions past a static defensive opponent at speeds between 4.5 and 5.5 meters per
      second under 2 different conditions, with and without ankle bracing. Peak
      mediolateral ground reaction force was recorded (as a unit of body weight) for
      each subject in both bracing and control conditions. The application of an
      Aircast brace significantly (P = 0.01) reduced peak mediolateral forces during
      cutting maneuvers compared with no brace. Results suggest that the application of
      an Aircast ankle brace significantly reduces PMGRF during cutting maneuvers
      around a static defensive opponent.

PMID- 20802286
TI  - Motivation of fitness center participants toward resistance training.
AB  - There is a need to better understand the behavior and sense of motivation of
      fitness center participants. The purpose of this study was to assess whether or
      not demographic characteristics and health self-determinism (intrinsic or
      extrinsic motivation) of fitness center participants were predictive of their
      levels of resistance training. A cross-sectional design was used; participants
      were recruited via the Internet to complete an online survey. There were 185
      participants (age = 39.1 +/- 11.3 years) in the study. The majority of
      respondents reported having carried out levels of resistance training that met
      national health organization recommendations. Regression analysis of the data
      revealed that health self-determinism predicted quantity of resistance training
      reported (p = 0.014), whereas demographics did not. Being intrinsically motivated
      to health self-determinism predicted meeting national resistance training
      recommendations compared to participants extrinsically motivated (p = 0.007). For
      those who work with fitness center participants, our findings are useful by
      identifying participants as a predominantly intrinsically motivated group of
      people that performs adequate quantities of resistance training; the methodology
      employed in this study can be used to identify participants in need of increased
      levels of resistance training and heightened sense of motivation to do so.

PMID- 20802287
TI  - Effects of different resistance training intensity on indices of oxidative
      stress.
AB  - The purposes of this study were (a) to determine whether acute resistance
      exercise training (RET) induces oxidative stress, (b) to determine whether
      chronic RET decreases oxidative stress level at rest condition in previously
      untrained men, and (c) also to investigate how the RET intensity influences the
      training-induced oxidative stress response. Sixteen young men who did not have
      RET experience in the past were randomly divided in 2 groups. Hypertrophy
      intensity group (n = 9) performed 3 sets of 12 repetitions at an intensity
      corresponding to 70% of 1 repetition maximum (1RM), whereas strength-intensity
      group (n = 7) performed 3 sets of 6 repetitions at an intensity corresponding to
      85% of 1RM. Resistance exercise training involved 6 exercises, and it was
      performed 3 times a week on nonconsecutive days for 6 weeks. Blood samples were
      obtained just before (pre-RET) and immediately after RET (post-RET) on the first
      day of the first week, on the last day of the fourth and sixth weeks. The results
      indicated that malondialdehyde (MDA) significantly decreased (p < 0.05) in both
      groups immediately after RET; however, there was no significant acute alteration
      in glutathione (GSH) level in both groups (p > 0.05). After 6 weeks of training,
      pre-RET values of MDA significantly decreased and pre-RET values of GSH
      significantly increased in both hypertrophy- and strength-intensity groups (p <
      0.05). These alterations occurred independently of training intensity. This study
      indicated that hypertrophy- and strength-intensity whole-body RET performed
      regularly for 6 weeks, decreased MDA concentration and increased GSH level in
      healthy young men. Results suggest that chronic RET has protective effects
      against oxidative stress similar to aerobic exercises and that these effects seem
      to be independent of the training intensity.

PMID- 20802288
TI  - The effect of a short-term combined conditioning training for the development of
      leg strength and power.
AB  - The aim of the study was to compare the effect of combined weight and pendulum
      training exercises with those isolated ones on muscle strength and vertical jump
      performance. A total of 38 young active men were divided into 4 groups performing
      different combinations of strength and power training and measured directly and 2
      weeks after the training program. Weight training and pendulum swing exercises,
      involving lower body during dynamic bounces, were used. Results of 1 repetition
      maximum (1RM) in full squat and squat jump with the barbell, maximal force
      measured during countermovement jump (CMJ), and hip and knee flexor and extensor
      isometric strength were analyzed. Significant differences (p <or= 0.05) in
      strength test (1RM squat, hip and knee flexor and extensor strength) were found
      when performing weight training (1RM-10.2%; maximal torques-23.2%). Positive
      significant increase (p <or= 0.05) in all strength and power parameters (maximal
      torques-from 2, 468.9 +/- 387.4 to 2, 712.4 +/- 501.6 Nxm; 1RM squat-from 93.9 +/
      15.0 to 111.4 +/- 15.6 kg; CMJ power-from 3, 050.7 +/- 478.5 to 3, 419.8 +/-
      506.6 W; CMJ jump height-from 48.8 +/- 4.1 to 53.4+/-3.0 cm) after the training
      program was found when combined training was used. Seated safety position during
      the pendulum swing is responsible for significant training effect with reduced
      loads. Plyometric pendulum swing training combined with traditional training can
      be an alternative, effective method to increase muscle strength and power during
      short pre or in-season mesocycles.

PMID- 20802289
TI  - Effects of different magnitudes of whole-body vibration on arm muscular
      performance.
AB  - The purpose of this study was to analyze the effects of different vibration
      magnitudes via feet on the number of repetitions performed, mean velocity, and
      perceived exertion during a set of elbow-extension exercise to failure (70% 1
      repetition maximum [1RM] load). Twenty recreationally active students (14 men and
      6 women) performed, in 3 different days, 1 elbow-extension set applying randomly
      1 of the 3 experimental conditions: high magnitude (HM; 50 Hz and 2.51 mmp-p;
      98.55 mxs-2), low magnitude (LM; 30 Hz and 1.15 mmp-p; 20.44 m.s-2) or control
      (Control, without vibration stimulus). Results indicate that the vibration via
      feet provides superimposed stimuli for elbow-extensor performance, enhancing the
      total number of repetitions performed in the HM and LM conditions, which was
      significantly higher (p <or= 0.05) than that performed in the Control condition
      (21.5 and 18.1%, respectively). Moreover, there was a significant increase (p
      <or= 0.05) in the average velocity for the whole set in the HM condition in
      comparison to the LM and Control conditions. This study provides evidence that an
      HM of vibration generates more neuromuscular facilitation than an LM. These data
      suggest that a vibration stimulus applied to the feet can result in positive
      improvements in upper body resistance exercise performance.

PMID- 20802290
TI  - Determination of ventilatory threshold through quadratic regression analysis.
AB  - Ventilatory threshold (VT) has been used to measure physiological occurrences in
      athletes through models via gas analysis with limited accuracy. The purpose of
      this study is to establish a mathematical model to more accurately detect the
      ventilatory threshold using the ventilatory equivalent of carbon dioxide
      (VE/VCO2) and the ventilatory equivalent of oxygen (VE/Vo2). The methodology is
      primarily a mathematical analysis of data. The raw data used were archived from
      the cardiorespiratory laboratory in the Department of Kinesiology at Midwestern
      State University. Procedures for archived data collection included breath-by
      breath gas analysis averaged every 20 seconds (ParVoMedics, TrueMax 2400). A ramp
      protocol on a Velotron bicycle ergometer was used with increased work at 25 W.min
      beginning with 150 W, until volitional fatigue. The subjects consisted of 27
      healthy, trained cyclists with age ranging from 18 to 50 years. All subjects
      signed a university approved informed consent before testing. Graphic
      scatterplots and statistical regression analyses were performed to establish the
      crossover and subsequent dissociation of VE/Vo2 to VE/VCO2. A polynomial trend
      line along the scatterplots for VE/VO2 and VE/VCO2 was used because of the high
      correlation coefficient, the coefficient of determination, and trend line. The
      equations derived from the scatterplots and trend lines were quadratic in nature
      because they have a polynomial degree of 2. A graphing calculator in conjunction
      with a spreadsheet was used to find the exact point of intersection of the 2
      trend lines. After the quadratic regression analysis, the exact point of VE/Vo2
      and VE/VCO2 crossover was established as the VT. This application will allow
      investigators to more accurately determine the VT in subsequent research.

PMID- 20802291
TI  - Specific factors that influence deciding the takeoff leg during jumping
      movements.
AB  - The definition of the dominant leg (lateral dominance) is not clear, and there
      has been little reporting related to lateral dominance in the legs. To uncover
      the practical factors influencing which leg to use as the takeoff leg in 1-legged
      jumping movements, this study aimed to investigate the subjective dominance side
      of fundamental movements and to examine the lateral dominance of motor functions
      between the takeoff leg and non-takeoff leg. The subjects consisted of 27 young
      men who exercised regularly. They had not trained particularly on unilateral
      jumping. Fifteen men are the athlete group (left-legged jumpers group [LG]) using
      a left leg and 12 men are the athlete group (right-legged jumpers group [RG])
      using a right leg as determined by a preliminary survey related to takeoff leg
      during high jump. The fundamental motions of the subjective dominant leg were
      investigated and the differences between the motor functions of takeoff and lead
      legs, such as sole shapes, single-leg vertical jump, 20-m hopping, ladder
      hopping, single-leg balance, and isokinetic strength were examined. It was found
      that many RG subjects (83%) tended to select the right leg for hopping, and many
      LG subjects (87%) tended to select the left leg for 1-legged balance. It was
      suggested that skilled movements show right-leg dominance in both takeoff leg
      groups. In the LG subjects, the left leg showed a higher value than the right leg
      in sole shape. The RG subjects showed a higher value in the right leg than in the
      left leg in a single-leg vertical jump. However, marked dominance was not found
      in the takeoff leg. The lower limbs may not show marked lateral dominance such as
      in the upper limbs.

PMID- 20802292
TI  - Evaluation of the field tests of flexibility of the lower extremity: reliability
      and the concurrent and factorial validity.
AB  - The purpose of this study was to evaluate the standard field tests of flexibility
      of the lower extremity through their (a) intratrial and test-retest reliability,
      (b) concurrent validity with respect to a high-precision 3D system for kinematic
      recording, and (c) factorial validity. Physically active men (n = 84) were tested
      over 2 separate sessions by means of standard simple devices (kinanthropometry,
      ruler, and protractor) on the following flexibility tests: leg raise in a supine
      position, hip abduction test, single-legged knee bend (SLKB), sideward leg splits
      (SdLS), sit and reach (SR), sideways leg splits, and lengthwise leg splits.
      Additionally, 17 participants were simultaneously tested by means of a laboratory
      3D kinematic analysis system. Most of the tests demonstrated high intratrial and
      test-retest reliability and concurrent validity. The exceptions were SLKB and SR
      tests that revealed not only a somewhat lower reliability but also a lower
      concurrent validity. For estimation of factorial validity, we applied a principal
      component analysis of the intercorrelations among the evaluated flexibility tests
      that revealed a single extracted principal component. Strong mutual relationships
      among them also suggest that very few of them, if not a single one, should be
      applied within the standard batteries of physical performance tests. We
      particularly recommend using SdLS over the most frequently used SR not only
      because of its relatively high reliability and validity but also because of its
      postural properties. Finally, we conclude that most of the standard field tests
      of flexibility of the lower extremity based on using inexpensive field equipment
      could be both reliable and valid and, therefore, justified for use in routine
      testing.

PMID- 20802293
TI  - Resistance analyses in highly experienced patients failing raltegravir,
      etravirine and darunavir/ritonavir regimen.
AB  - OBJECTIVES: ANRS 139 TRIO trial was a phase II noncomparative trial that
      evaluated in highly experienced patients, a combination of raltegravir,
      etravirine and darunavir boosted with ritonavir. We analyzed emergence of
      resistant viruses at the time of virological failure and investigated the impact
      of baseline integrase polymorphisms on virological failure occurrence. METHODS:
      Bulk sequencing of protease, reverse transcriptase and integrase genes was
      performed for 103 patients at baseline and 14 patients at the time of virological
      failure. Additionally, integrase clonal analyses were performed at baseline and
      at virological failure in patients with successful integrase gene amplification.
      Impact of baseline integrase polymorphisms on virological failure occurrence was
      analyzed using Fisher exact and Wilcoxon tests. RESULTS: In the 14 failing
      patients median viral load at virological failure was 90 copies/ml (interquartile
      range = 60-783). Emergence of darunavir and etravirine resistance mutations was
      observed at virological failure in only one and three patients, respectively.
      Raltegravir resistance mutations were found neither at baseline nor at the time
      of virologic failure. Integrase clonal analyses showed neither the presence nor
      the selection of minority variants carrying raltegravir resistance mutations at
      baseline or at virological failure. No impact of baseline integrase polymorphisms
      was observed on virological failure either at week 24 or at week 48. CONCLUSION:
      Virological failure occurred in a small proportion of patients with low viral
      load. No raltegravir resistance mutations were observed using bulk sequencing or
      clonal analyses, and darunavir and etravirine resistance-associated mutations
      were detected in only one and three patients, respectively at virological
      failure. No impact of baseline integrase polymorphism was observed on virological
      failure occurrence.

PMID- 20802295
TI  - Pandemic influenza A (H1N1) in HIV-1-infected patients.
AB  - OBJECTIVE: To characterize the clinical presentation, course and mortality of
      pandemic influenza in HIV-1-infected patients in Santiago, Chile. METHODS:
      Prospective observational study. RESULTS: Thirty patients were included (three
      hospitalized), 93% were on HAART, mean CD4(+) cell count was 423 cells/MUl and
      viral load was undetectable in 77% of patients. All patients had fever, 90% had
      cough, 80% had myalgias, 70% had pharyngeal congestion, 47% had coryza, 47% had
      odynophagia, 37% had headache and 23% had vomiting. Four patients developed
      pneumonia. All patients received antiviral therapy and no patient died.
      CONCLUSIONS: HIV patients infected by the new influenza A pandemic (H1N1) virus
      behave similarly to the general population.

PMID- 20802294
TI  - Polymorphism in tumor necrosis factor-related apoptosis-inducing ligand receptor
      1 is associated with poor viral response to interferon-based hepatitis C virus
      therapy in HIV/hepatitis C virus-coinfected individuals.
AB  - OBJECTIVE(S): HIV/hepatitis C virus (HCV) coinfection causes accelerated liver
      disease compared to HCV monoinfection, and only 30-60% of HIV/HCV-coinfected
      individuals respond to HCV therapy with pegylated interferon and ribavirin. There
      are currently no biomarkers that predict treatment response in these coinfected
      patients. DESIGN: We investigated whether there is an association between HCV
      treatment response and SNPs of apoptosis-related genes during HIV/HCV
      coinfection. METHOD: Genomic DNA from 53 HIV/HCV-coinfected individuals was
      analyzed for 82 SNPs of 10 apoptosis-related genes. RESULTS: We found that the
      presence of the rs4242392 SNP in tumor necrosis factor receptor superfamily,
      member 10a (TNFRSF10A), which encodes for tumor necrosis factor-related apoptosis
      inducing ligand receptor 1, predicts poor outcome to HCV therapy, in HIV/HCV-co
      infected patients [odds ratio 5.91 (95% confidence interval 1.63-21.38, P =
      0.007)]. CONCLUSION: The rs4242392 SNP of the tumor necrosis factor-related
      apoptosis-inducing ligand receptor 1 gene predicted poor interferon-based HCV
      treatment response in HIV/HCV-coinfected patients.

PMID- 20802296
TI  - Distinct differentiation profiles of HIV-Gag and Nef-specific central memory CD8+
      T cells associated with HLA-B57/5801 and virus control.
AB  - OBJECTIVES: A superior capacity of controlling HIV has been attributed to CD8(+)
      T cells directed against HIV-Gag compared to Nef, particularly in the context of
      some protective human leukocyte antigen (HLA) alleles. To further elucidate this
      protective effect, we compared the multifunctional and differentiation
      characteristics of CD8(+) T cells specific for HIV-Gag and Nef in HLA-B57/5801
      positive and negative nonprogressors. METHODS: A head-to-head comparison of
      CD8(+) T cells specific for HIV-Gag and Nef frequencies, cytokine production and
      differentiation was conducted, in 11 HLA-B57/5801 and 11 HLA-B57/5801 HIV
      infected individuals selected from a cohort of 53 nonprogressors by using IFN
      gamma-ELISpot assay and flow cytometry analysis of intracellular cytokine
      production and differentiation profile. Correlations with HIV parameters were
      studied. RESULTS: Frequencies of Gag-specific but not of Nef-specific CD8(+) T
      cells correlated with peripheral blood mononuclear cell (PBMC)-associated HIV
      DNA. The HIV-Gag and Nef-specific CD8(+) T cells did not differ for IL-2
      production in either HLA-B57/5801 or HLA-B57/5801 individuals. The IFN-gamma
      producing Gag-specific CD8(+) T cells in HLA-B57/5801 individuals significantly
      differed from their Nef-specific counterparts by displaying higher proportions of
      central memory CD45RACCR7 cells positive for CD27(+). This differentiation
      pattern was not observed in HLA-B57/5801 individuals. Only these HLA-B57/5801
      positive Gag-specific CD27(+) central memory CD8(+) T cells, but not their Nef
      specific counterparts, negatively correlated with cell-associated HIV-DNA.
      CONCLUSION: HLA-B57/5801 drives a preferential CD27(+) differentiation of central
      memory CD8(+) T cells directed against HIV-Gag but not Nef that may contribute to
      the ability of Gag-specific CD8(+) T cells to better control HIV in HLA-B57/5801
      nonprogressors.

PMID- 20802297
TI  - Efficacy of darunavir/ritonavir maintenance monotherapy in patients with HIV-1
      viral suppression: a randomized open-label, noninferiority trial, MONOI-ANRS 136.
AB  - BACKGROUND: Darunavir/ritonavir (darunavir/r) maintenance strategy, in patients
      with suppressed HIV RNA viremia, is a potential long-term strategy to avoid
      nucleoside analogue toxicities and to reduce costs. METHODS: MONOtherapy
      Inhibitor protease is a prospective, open-label, noninferiority, 96-week safety
      and efficacy trial in virologically suppressed patients on triple therapy who
      were randomized to a darunavir/r triple drug regimen or darunavir/r monotherapy.
      The primary endpoint was the proportion of patients with HIV RNA less than 400
      copies/ml at week 48; treatment failure was defined as two consecutive HIV RNA
      more than 400 copies/ml (time to loss of virologic response) or any change in
      treatment. The trial had 80% power to show noninferiority for the monotherapy arm
      (delta =-10%, 90% confidence interval). RESULTS: A total of 242 patients were
      screened, 225 of whom were randomized. In the per protocol efficacy analysis,
      treatment success was 99% on darunavir/r triple drug versus 94% on darunavir/r
      monotherapy (delta = -4.9%, 90% confidence interval, from -9.1 to -0.8). Similar
      results were found in intent-to-treat population (92 versus 87.5%, delta = -4.5%,
      90% confidence interval from -11.2 to 2.1). Three patients experienced virologic
      failure on darunavir/monotherapy and none on darunavir/r triple drug. No
      resistance to protease inhibitor emerged in patients with plasma viral load above
      50 copies/ml. The two groups did not differ in the number of serious adverse
      events. CONCLUSION: Darunavir/r monotherapy exhibited efficacy rate over 85% with
      concordant results in the magnitude of difference with darunavir/r triple drug
      regimen in both intent-to-treat and per protocol analyses, but discordant
      conclusions with respect to the noninferiority margin. Patients failing on
      darunavir/r monotherapy had no emergence of new darunavir resistance mutations
      preserving future treatment options.

PMID- 20802299
TI  - The nipple-areola complex epidermis: a prospective systematic study in adult
      autopsies.
AB  - The prevalence of different types of clear cells and of the mite Demodex in the
      nipple-areola complex of adult autopsies of both sexes not suffering from breast
      cancer was studied in a total of 140 nipples. The epidermis of the nipple-areola
      complex shows squamous cells and 3 types of clear cells: Toker cells, pagetoid
      dyskeratosis cells, and signet ring-like cells. Toker cells were identified by
      standard light microscopy in 13 of 140 nipples (9.3%). Reactivity of these cells
      for CK7 was observed in 35 nipples (25%). They are derived from the lactiferous
      duct epithelium. Pagetoid dyskeratosis cells were identified in 56 of 140 nipples
      (40%). In 12 nipples, these cells were conspicuous (8.6%). It is suggested that
      the proliferation of these cells is induced by friction. Signet ring-like cells
      were identified in 71 nipples (50.7%). In 2 nipples, these cells were conspicuous
      (1.4%). They are a consequence of artefact related to formalin fixation. The
      prevalence of all these clear cells has no relationship with gender. Routine
      histopathological examination is usually enough to distinguish the characteristic
      features of the clear cells involving the nipple epidermis and permits
      differentiation of other entities with epidermal pale cells. Demodex mites were
      observed in 58 nipple-areola complexes (41.4%). They were more common in male
      nipple-areola complexes (P < 0.05). The prevalence of these mites was seen to
      remain steady along the years since the third decade. Demodex mites are common
      parasites of human nipple and are apparently of no pathologic significance.

PMID- 20802300
TI  - Acquired lymphangiectasias in genital lichen sclerosus.

PMID- 20802298
TI  - Randomized controlled study demonstrating failure of LPV/r monotherapy in HIV:
      the role of compartment and CD4-nadir.
AB  - BACKGROUND: Long-term side-effects and cost of HIV treatment motivate the
      development of simplified maintenance. Monotherapy with ritonavir-boosted
      lopinavir (LPV/r-MT) is the most widely studied strategy. However, efficacy of
      LPV/r-MT in compartments remains to be shown. METHODS: Randomized controlled open
      label trial comparing LPV/r-MT with continued treatment for 48 weeks in treated
      patients with fully suppressed viral load. The primary endpoint was treatment
      failure in the central nervous system [cerebrospinal fluid (CSF)] and/or genital
      tract. Treatment failure in blood was defined as two consecutive HIV RNA levels
      more than 400 copies/ml. RESULTS: The trial was prematurely stopped when six
      patients on monotherapy (none in continued treatment-arm) demonstrated a viral
      failure in blood. At study termination, 60 patients were included, 29 randomized
      to monotherapy and 13 additional patients switched from continued treatment to
      monotherapy after 48 weeks. All failures occurred in patients with a nadir CD4
      cell count below 200/microl and within the first 24 weeks of monotherapy. Among
      failing patients, all five patients with a lumbar puncture had an elevated HIV
      RNA load in CSF and four of six had neurological symptoms. Viral load was fully
      resuppressed in all failing patients after resumption of the original combination
      therapy. No drug resistant virus was found. The only predictor of failure was low
      nadir CD4 cell count (P < 0.02). CONCLUSION: Maintenance of HIV therapy with
      LPV/r alone should not be recommended as a standard strategy; particularly not in
      patients with a CD4 cell count nadir less than 200/microl. Further studies are
      warranted to elucidate the role of the central nervous system compartment in
      monotherapy-failure.

PMID- 20802301
TI  - The reports by Yanagihara et Al on primary cutaneous localized amyloidosis
      surrounding elastic fibers.

PMID- 20802302
TI  - Diffuse erythema and dry scales in a female infant. X-linked dominant Conradi
      Hunermann-Happle (CHH) syndrome.

PMID- 20802303
TI  - Benign "waxing-waning" vascular proliferations in previously irradiated skin.

PMID- 20802304
TI  - The dysplastic nevus controversy: It is not about the nevus per se but one's
      belief in the multistep tumorigenesis theory.

PMID- 20802305
TI  - Cutaneous colesional acquired immunodeficiency syndrome associated Kaposi sarcoma
      and cryptococcosis.
AB  - The clinicopathologic features of 4 AIDS patients with cutaneous colesional
      Kaposi sarcoma (KS) and cryptococcosis, a rare phenomenon, are described.
      Biopsies from 3 patients who were highly active antiretroviral therapy (HAART)
      naive demonstrated predominant KS with a conspicuous spindle cell component and
      small aggregates of cryptococcal yeasts in 2 biopsies and predominant gelatinous
      cryptococcosis with attenuated KS spindle cells in 1 biopsy. One patient was
      HAART exposed. He had childhood pulmonary tuberculosis, was treated for
      disseminated cutaneous cryptococcosis 18 months earlier and presented with
      cutaneous lesions, odynophagia and massive cervical lymphadenopathy in the eighth
      week of HAART, after achieving viral suppression and a CD4 cell increase from 28
      to 184 cells/MUL. His skin biopsy demonstrated a dense lymphoplasmacytic
      infiltrate, neutrophils, and granulomas with admixed aggregates and single
      Cryptococcus neoformans and focal aggregation of human herpes virus 8
      immunopositive spindle cells. Acid fast bacilli were not identified and
      mycobacterial molecular studies were negative. The features were compatible with
      cutaneous cryptococcal immune reconstitution inflammatory syndrome. His nodal and
      oropharyngeal biopsies demonstrated dense mixed, including granulomatous,
      inflammation with few cryptococcal yeasts and acid fast bacilli, confirmed to be
      Mycobacterium tuberculosis on polymerase chain reaction testing, without KS.
      These features were also compatible with immune reconstitution inflammatory
      syndrome, but the exact role of each infection in the extracutaneous sites was
      unconfirmed. Colesional KS and cryptococcosis served as the sentinel lesion of
      AIDS in 3 patients and of immune reconstitution inflammatory syndrome in 1
      patient.

PMID- 20802306
TI  - Cardiovascular and economic outcomes after initiation of atorvastatin versus
      simvastatin in an employed population stratified by cardiovascular risk.
AB  - The relative effects of atorvastatin and simvastatin among higher- and lower-risk
      patients are not well characterized. This study compared cardiovascular (CV) risk
      and direct and indirect costs among higher- and lower-risk employees initiating
      atorvastatin vs. simvastatin. Using a large employer claims database (1999-2006),
      employees were stratified as 1) high-risk employees with prior CV events,
      diabetes, or renal disorders; and 2) low- to intermediate-risk employees without
      these conditions. Propensity score matching was used, and 2-year outcomes were
      compared between matched cohorts. Indirect costs included disability payments and
      medically related absenteeism. Drug costs were imputed with recent prices to
      account for availability of generic simvastatin. Among 4167 matched pairs of high
      risk employees, atorvastatin use was associated with a numerically lower risk of
      CV events (17.6 versus 18.4%, P = 0.37), higher direct medical costs ($17,590
      versus $17,377, P = 0.002), numerically lower indirect costs ($4830 versus $4989,
      P = 0.29), and higher total costs by $54 ($22,420 versus $22,366, P = 0.034). The
      majority of high-risk employees (62%) received low initial statin doses
      (atorvastatin = 10 mg or simvastatin = 20 mg). Among 9326 matched pairs of low-
      to intermediate-risk employees, atorvastatin use was associated with a lower risk
      of CV events (3.1% versus 3.7%, P = 0.030), lower direct medical costs ($8400
      versus $8436, P < 0.001), numerically lower indirect costs ($2781 versus $2807; P
      = 0.12), and lower total costs by $61 ($11,181 versus $11,243, P < 0.001). These
      results suggest that formulary policies reserving atorvastatin for higher-risk
      patients may not be cost-saving from the employer perspective.

PMID- 20802308
TI  - Diagnosis of Pallister-Killian syndrome by array comparative genome hybridization
      from a spleen sample.

PMID- 20802307
TI  - Quetiapine anxiolytic-like effect in the Vogel conflict test is serotonin
      dependent.
AB  - There is growing evidence to show that atypical antipsychotic quetiapine might
      exert an anxiolytic effect in patients. Nevertheless, the mechanism underlying
      this effect has not yet been fully explored. Like other anxiolytic drugs,
      quetiapine exhibits partial agonistic activity toward serotonergic 1A (5HT1A)
      receptors. The involvement of the serotonin system in anxiety, particularly of
      5HT1A receptors, has been widely documented. In this study we have investigated
      whether different doses of quetiapine (5, 10, and 30 mg/kg, oral gavage)
      administered to C57BL6/N mice could produce an anxiolytic effect in the Vogel
      conflict test, a classical model of anxiety, and whether or not the selective
      5HT1A antagonist WAY100635 (0.1 mg/kg, subcutaneously) might prevent such an
      effect. Our results show that 10 mg/kg quetiapine exhibits an anxiolytic effect,
      that is, at least in part, 5HT1A-mediated, because it is completely eliminated by
      WAY100635.

PMID- 20802309
TI  - Subcutaneous nodules, arthropathy, coarse face, cataract and glaucoma: a newly
      recognized syndrome.

PMID- 20802310
TI  - Nicolaides-Baraitser syndrome: two new cases with autism spectrum disorder.
AB  - Nicolaides-Baraitser syndrome is a rare clinical condition characterized by
      mental retardation with impairment of expressive language, short stature,
      microcephaly, sparse hair, typical facial dysmorphisms, and interphalangeal joint
      swellings. To date 24 cases have been reported, most of them being sporadic. The
      genetic background of Nicolaides-Baraitser syndrome is unclear in terms of cause
      and mode of inheritance, one of the more probable explanations is de novo
      mutation of a dominant gene. Some reported patients presented autistic features,
      although in none of these patients was the diagnosis of autism spectrum disorder
      formally made. We describe two unrelated patients with clinical features
      suggesting Nicolaides-Baraitser syndrome and, in addition, autism spectrum
      disorder is defined by the presence of the three cardinal core features:
      qualitative impairments in social, communicative, and behavioral development.

PMID- 20802311
TI  - Posterior dislocation of descemet stripping automated endothelial keratoplasty
      graft can lead to retinal detachment.
AB  - PURPOSE: To describe traction retinal detachment as a complication of posterior
      dislocation of Descemet stripping automated endothelial keratoplasty (DSAEK)
      graft. METHODS: Vitrectomy surgery was performed in 3 eyes that developed
      posterior dislocation of DSAEK graft. Intraoperatively, the corneal tissue was
      found to be adherent to the retina. In 2 cases, a retinal detachment with
      proliferative vitreoretinopathy (PVR) was already present and the donor DSAEK
      flap was found to be fused with the retina. In 1 case, the retina was attached at
      the time of surgery but PVR subsequently developed despite near total removal of
      the graft, requiring an additional procedure to achieve retinal reattachment.
      RESULTS: Corneal tissue removal with a vitreous cutter was attempted in all
      cases. Residual tissue that had fused with the retina was left in place. Retinal
      reattachment was achieved with silicone oil injection in 2 cases and scleral
      buckle alone in 1 case. CONCLUSIONS: Posterior segment dislocation of a DSAEK
      flap and its adherence to the retina may cause PVR and traction retinal
      detachment. Early removal is warranted when dislocation occurs.

PMID- 20802312
TI  - Histopathological study of delayed regraft after corneal graft failure.
AB  - PURPOSE: To evaluate the histopathological features of corneal graft failures
      over time. METHODS: A single-center retrospective analysis was performed on
      corneal specimens diagnosed as corneal graft failure retrieved from The Henry C.
      Witelson Ophthalmic Pathology Laboratory and Registry (Montreal, Canada) over a 9
      year period. The corneal buttons were divided into 3 different groups according
      to the time between the diagnosis of corneal graft failure and regraft. Corneal
      specimens obtained during keratoplasty were subjected to hematoxylin and eosin
      and periodic acid-Schiff. Five different histopathological findings were
      evaluated in each specimen. RESULTS: Overall, the most common histopathological
      finding was endothelial decompensation (97.2%). Subepithelial pannus (38.9%),
      vessels in the corneal stroma (11.1%), and anterior synechiae (2.8%) were the
      other present findings. The inflammatory reaction was considered discrete in
      83.3% of the cases. The only significant histopathological finding correlated
      with time was the presence of vessels in the corneal stroma (P = 0.0092).
      CONCLUSIONS: Corneal neovascularization, represented by the presence of vessels
      in the corneal stroma, was the only histopathological finding correlated with
      time. Because it is a known factor of poor prognosis, our findings strongly
      support that early regraft has higher chances of success.

PMID- 20802313
TI  - Histopathological changes of cornea in long-term sympathetic ophthalmitis.
AB  - PURPOSE: To report the histopathological changes occurring in the cornea in
      sympathetic ophthalmitis. METHODS: Observational case series of 3 patients with
      sympathetic ophthalmitis who were treated with penetrating keratoplasty. We
      report the histopathological features of the cornea. RESULTS: In all 3 cases, the
      epithelium was edematous and bullous with extensive loss of the Bowman layer and
      calcification of the superficial stroma in all the 3 eyes. The deep stroma was
      unremarkable in appearance. Descemet membrane showed thickening in 2 of the
      corneas with nodular excrescences and folds noted in 1 of the specimens. The
      endothelium was attenuated with some residual cells containing pigment granules
      in 1 case. CONCLUSIONS: Endothelial loss and development of bullous keratopathy
      associated with band keratopathy are predominate histopathological features of
      the cornea. These changes are nonspecific and reflect a chronic anterior uveitis.

PMID- 20802314
TI  - The antigenicity of ex vivo cultivated human corneal limbal epithelial and
      stromal cells: temporal changes in vitro.
AB  - PURPOSE: To investigate the effect of ex vivo culture on the expression of human
      leukocyte antigen (HLA) in human corneal limbal epithelial cells (LECs), and to
      evaluate the expression of HLA and costimulatory molecules on human corneal
      limbal stromal cells (LSCs). METHODS: The expression of HLA-ABC and HLA-DR were
      evaluated using flow cytometry on cultured human LECs and LSCs after serial
      passage and compared with that on freshly isolated cells. Additionally, the
      expression of costimulatory molecules CD80, CD86, CD40, and immunoregulatory
      molecule HLA-G were investigated on LSCs with or without an addition of
      interferon (IFN) gamma (250 U/mL, 4 days). RESULTS: HLA-ABC and HLA-DR were
      expressed in 99.12 +/- 1.02% and 25.86 +/- 4.34% of freshly isolated LECs,
      respectively. After culture, the HLA-DR-expressing cells significantly decreased
      with serial passage, whereas the percentage of HLA-ABC-expressing cells did not
      change. More than 90% of LSCs expressed HLA-ABC and HLA-G, whereas the expression
      of HLA-DR, CD80, CD86, and CD40 was negligible. This expression profile did not
      change after serial passage. However, the treatment with IFN-gamma induced a
      significant increase in HLA-DR (0.17% vs. 17.68%) and CD40 (0.19% vs. 13.19%)
      expression on LSCs. CONCLUSIONS: The immunogenicity of LECs can be lowered after
      ex vivo cultivation, whereas LSCs can be immunogenic in the presence of IFN
      gamma.

PMID- 20802315
TI  - Influence of alkyl chain length of benzalkonium chloride on acute corneal
      epithelial toxicity.
AB  - PURPOSE: To evaluate acute corneal epithelial toxicity induced by benzalkonium
      chloride (BAC) homologs with different alkyl chain lengths using an in vivo
      electrophysiological method. METHODS: BAC homologs with C12, C14, and C16 alkyl
      chain lengths were used at concentrations of 0.0025%, 0.005%, and 0.01%,
      respectively. Cytotoxicity of BAC homologs on the normal rabbit corneal
      epithelial cells was examined by using a WST-1 assay. Corneal transepithelial
      electrical resistance (TER) was measured in living Japanese white rabbits by 2
      Ag/AgCl electrodes placed in the anterior aqueous chamber and on the cornea. TER
      changes were then evaluated after a 60-second exposure to these BAC homologs.
      Morphological changes in corneal epithelium after exposure to the BAC homologs
      were examined using scanning electron microscopy. The antimicrobial activity of
      BAC homologs against Escherichia coli was also assessed. RESULTS: All BAC
      homologs caused cytotoxicity and corneal barrier dysfunction in a concentration
      dependent manner. However, the degree of corneal toxicity differed among the BAC
      homologs. Based on cytotoxicity and TER measurement, C14-BAC caused the greatest
      corneal impairment followed in order of severity by mixed BAC/C16-BAC and C12
      BAC. Scanning electron microscopy images indicated an intact corneal epithelium
      after exposure to 0.005% C12-BAC, whereas 0.005% C14-BAC damaged the epithelium.
      There were no remarkable differences noted in the antimicrobial activity among
      the BAC homologs. CONCLUSIONS: Acute corneal epithelial toxicity induced by BAC
      homologs depends on the alkyl chain length. Thus, the use of C12-BAC instead of
      commercially available BAC is potentially safer for patients undergoing
      ophthalmological pharmacotherapy.

PMID- 20802316
TI  - Perilimbal bevacizumab injection for interface neovascularization after deep
      anterior lamellar keratoplasty.
AB  - PURPOSE: To evaluate the effect of perilimbal bevacizumab injection on
      neovascularization at the interface of donor and recipient tissues after deep
      anterior lamellar keratoplasty (DALK). METHODS: This interventional case series
      included 4 patients with interface neovascularization after DALK (3 patients with
      advanced keratoconus and 1 patient with scarring because of herpetic keratitis).
      Bevacizumab (2.5 mg/0.1 mL) was injected subconjunctivally near the limbus
      adjacent to the abnormal blood vessels. Depending on regression of new vessels,
      injections were repeated. If neovascularization occurred in more than 1 quadrant,
      injections were administered at 2 sites (2.5 mg for each injection). Total
      corneal neovascularization, longest neovascular length, and degree of neovascular
      circumference were evaluated by digital slit lamp corneal photography before
      injection and 1 week, 1, 3, and 6 months afterward. RESULTS: The mean follow-up
      period was 14 +/- 7.52 months from the first bevacizumab injection. Corneal
      neovascularization, on average,was 33.70% +/- 7.8% (SD) of the total corneal
      surface before the injections, which decreased to 4.83% +/- 3.3% (P = 0.005, t
      test) at the last follow-up examination. Mean degree of neovascularized
      circumference decreased from 165 degrees before injection to 77.5 degrees (P =
      0.023) at the last follow-up examination. Mean longest neovascularized length
      decreased from 6.714 mm before injection to 1.497 mm (P = 0.021) at the last
      follow-up examination. At the end of the study, all patients had clear grafts
      with no sign of graft failure. Mean best-corrected visual acuity before injection
      was 20/100, which improved to 20/30 at the last examination. CONCLUSIONS: This
      small case series suggests that perilimbal bevacizumab injection is safe and
      effective for partial regression of new blood vessels at the interface of donor
      and recipient tissues after DALK and may effectively prevent graft rejection.

PMID- 20802317
TI  - Six-month clinical outcomes of customized treatments minimized for depth and time
      in laser corneal refractive surgery.
AB  - PURPOSE: Evaluating the application of 2 methods for minimizing the ablated
      tissue upon objective minimization of depth and time of Zernike-based customized
      ablations. SETTING: Muscat Eye Laser Center, Muscat, Sultanate of Oman. METHODS:
      Recently developed algorithms for selection of Zernike terms in customized
      treatments for refractive surgery were used. Clinical outcomes and tissue-saving
      attributes were evaluated on 2 groups [minimize depth (MD) and minimize volume
      (MV); 30 eyes each], plus a control group [corneal wavefront (CW); 30 eyes] with
      conventional customized approach. Clinical outcomes were evaluated in terms of
      predictability, safety, and contrast sensitivity and tissue-saving attributes in
      terms of saved depth and time for each condition (in micrometers, seconds, and
      percentage) and whether minimized depth or time were less than required for
      equivalent noncustomized treatments. RESULTS: Ninety-three percent of treatments
      in the CW group, 93% in the MD group, and 100% in the MV group were within 0.50
      diopters of spherical equivalent (SEq) postoperatively. Forty percent of
      treatments in the CW group, 34% in the MD group, and 47% in the MV group gained
      at least 1 line of best spectacle-corrected visual acuity postoperatively. Tissue
      saving attributes showed an average saved depth of 8 MUm (1-20 MUm) and a saved
      time of 6 seconds (1-15 seconds) in the MD group and 6 MUm (0-20 MUm) and 8
      seconds (2-26 seconds) in the MV group. Proposed corrections were always less
      deep and shorter than full wavefront corrections. In 43% of the MD cases,
      corrections were less deep, and in 40% of the MV cases, corrections were shorter
      than equivalent aberration-free treatments. CONCLUSION: The minimization
      techniques compared here effectively reduced depth and time needed for ablation
      (up to a maximum of 50% and by 15% in average) without negatively affecting
      clinical outcomes postoperatively, yielding results equivalent to those of the
      full customization group.

PMID- 20802318
TI  - Is there a change of corneal thickness in uveitis with Behcet disease?
AB  - PURPOSE: To report the measurements of central corneal thickness (CCT) in uveitic
      eyes with Behcet disease (BD) and compare it with age- and sex-matched healthy
      controls. MATERIALS AND METHODS: This study included 69 eyes with ocular BD with
      no history of corneal disease, glaucoma, or ocular surgery and 50 eyes of healthy
      controls. Eyes with ocular BD were subdivided into active and inactive groups.
      Active group was defined as the presence of anterior uveitis or panuveitis,
      whereas inactive group was defined as having had at least 1 previous attack and
      absence of any active inflammation in the eye within the last 3 months. CCT was
      measured with ultrasonic pachymeter. Statistical analyses were performed, and P <
      0.05 was considered statistically significant. RESULTS: Active group had 24
      patients and inactive group had 45 patients. Demographic characteristics of
      patients with ocular BD and control subjects were similar (P > 0.05). There was
      no significant difference in respect to the disease duration between active and
      inactive groups (P = 0.160). The mean CCT was significantly greater in active
      group (584.75 +/- 20.94 MUm) than in inactive group (540.55 +/- 36.16 MUm) and
      control group (543.04 +/- 25.35 MUm) (P = 0.0001). CONCLUSIONS: We found that
      eyes with active BD had increased CCT because of active inflammation when
      compared with inactive and control groups, and mean CCT of inactive BD was
      normal. Therefore, we assume that CCT is in normal range in the inactive phase,
      and recurrent uveitis does not lead to a permanent change in CCT in BD.

PMID- 20802319
TI  - Association between unilateral quiescent stromal herpetic keratitis and bilateral
      dry eyes.
AB  - PURPOSE: According to our clinical observation, patients with quiescent herpes
      simplex virus (HSV) stromal keratitis often seem to present with signs of dry eye
      in the contralateral eye. Our goal was to compare dry eye signs and symptoms in
      both eyes of patients with quiescent HSV stromal keratitis with those of age- and
      sex-matched control subjects with healthy corneas. METHODS: A case-control study
      with 24 subjects per group. RESULTS: The average age of 10 men and 14 women in
      each group was 58 years. The HSV eye of cases was first compared with the
      contralateral eye with a healthy cornea. As expected, the HSV eye had a
      significantly lower corneal sensation threshold (P = 0.001); no significant
      difference was however found for Schirmer tests done with anesthesia (basal tear
      secretion) and without anesthesia, tear breakup time, mucus and debris in the
      tear film, and eyelid margin redness or swelling. Then, the HSV eye of cases was
      compared with the right eye of controls, whereas the healthy eye of cases was
      compared with the left eye of controls. Patients with unilateral quiescent HSV
      stromal keratitis had significantly lower bilateral Schirmer tests both with
      anesthesia (P = 0.001) and without anesthesia (P = 0.02). Dry eye symptoms of the
      healthy cornea of cases and those of controls did not differ significantly.
      CONCLUSIONS: Both eyes of patients with quiescent HSV stromal keratitis in our
      population were dry even if many patients with HSV stromal keratitis did not have
      symptoms in their fellow eye.

PMID- 20802320
TI  - The association of keratoconus with immune disorders.
AB  - PURPOSE: To evaluate the association between keratoconus (KC) and immune
      disorders (IDs). METHODS: A retrospective observational case-control study of all
      the members in the Central District of Clalit Health Services in Israel who were
      diagnosed to have KC (years 2000-2007; n = 426) and 1704 age- and gender-matched
      controls. We calculated the prevalence of the following IDs: rheumatoid
      arthritis, ulcerative colitis, arthropathy, amyloidosis, systemic lupus
      erythematosus, celiac disease, multiple sclerosis, myasthenia gravis, polymyalgia
      rheumatica, idiopathic thrombocytopenic purpura, Crohn disease, Hashimoto
      thyroiditis, autoimmune hepatitis, irritable bowel syndrome, asthma, and
      environmental allergy. The odds ratio (OR) of having IDs among patients with KC
      was compared with controls. RESULTS: The association between KC and the following
      IDs was statistically significant: rheumatoid arthritis [OR = 8.1; 95%
      (confidence interval) CI: 1.5-44.2], ulcerative colitis (OR = 12.1; CI: 1.3-116),
      autoimmune chronic active hepatitis (OR = 6; CI: 1.01-36), Hashimoto thyroiditis
      (OR = 2.0; CI: 1.2-3.3), arthropathy (OR = 1.4; CI: 1.1-1.8), asthma (OR = 2.1;
      CI: 1.4-3.2), environmental allergy (OR = 1.3; CI: 1.02-1.75), and irritable
      bowel syndrome (OR = 5; CI: 2.1-12.1). Two autoimmune diseases, multiple
      sclerosis (OR = 2; CI: 0.2-22) and Crohn disease (OR = 1.6; CI: 0.3-8.3), were
      more prevalent among patients with KC but did not reach statistical significance.
      CONCLUSION: Some strong associations between KC and several immune conditions of
      autoimmune diseases and allergic IDs may point to the role of the immune system
      in the pathogenesis of KC.

PMID- 20802321
TI  - Nona-D-arginine amide suppresses corneal cytokines in Pseudomonas aeruginosa
      keratitis.
AB  - PURPOSE: Nona-D-arginine (D9R) amide suppressed interleukin 1beta production
      during Pseudomonas aeruginosa corneal infection. The purpose of this study was to
      determine the cellular disposition of D9R and its effect on other inflammatory
      mediators induced by infection. METHODS: Mouse eyes received 5 MUL of either
      phosphate-buffered saline (PBS, pH 7.4) or 100-MUM D9R hourly for 5 hours (total
      of 6 drops per eye) immediately after corneal wounding and infection with 1 * 10
      colony-forming units (CFUs) of P. aeruginosa strain PAO1. At 6, 12, and 24 hours
      postinfection, eyes were scored on a scale of 0 (normal eye) to +4 (corneal
      perforation). After scoring, mice were killed and eyes enucleated. Whole eyes
      were used for determining viable CFUs per eye. Corneas were excised for
      quantitation of tumor necrosis factor alpha, interferon gamma, interleukin 10,
      and granulocyte-macrophage colony-stimulating factor. The fate of D9R in cells
      was determined using a labeled peptide. RESULTS: Eyes treated with D9R had
      significantly lower disease scores (P <= 0.001) and fewer CFUs (P <= 0.01) than
      those in PBS-treated eyes. No corneal cytokines were detected in any D9R-treated
      eyes. In contrast, beginning at 12 hours postinfection, increasing amounts of
      tumor necrosis factor alpha, interleukin 10, and granulocyte-macrophage colony
      stimulating factor were detectible in corneas of PBS-treated eyes. Within 60
      minutes, D9R accumulated in the cell nucleus and nucleolus and remained for over
      24 hours. CONCLUSION: D9R reduces the severity of P. aeruginosa ocular infection
      in part by reducing bacterial burden and in part by controlling a destructive
      proinflammatory response. D9R might be a useful alternative to steroids in
      treating other inflammation-mediated pathologies of the eye.

PMID- 20802322
TI  - Fluids after cardiac surgery: a pilot study of the use of colloids versus
      crystalloids.
AB  - OBJECTIVES: To determine whether a starch solution for volume resuscitation in a
      flow-based protocol improves circulatory status better than a crystalloid
      solution, as defined by the need for catecholamines in patients the morning after
      cardiac surgery, and whether this can be performed without increased morbidity.
      DESIGN: Concealed, randomized, double-blind, controlled trial. PARTICIPANTS: Two
      hundred sixty-two patients who underwent cardiac surgery at a tertiary care
      hospital. INTERVENTIONS: Based on predefined criteria indicating a need for
      fluids, and a nurse-delivered algorithm that used central venous pressure and
      cardiac index obtained from a pulmonary artery catheter, patients were allocated
      to receive 250-mL boluses of 0.9% saline or a 250-molecular weight 10% solution
      of pentastarch. RESULTS: Two hundred thirty-seven patients received volume
      boluses: 119 hydroxyethyl starches and 118 saline. Between 8:00 am and 9:00 am
      the morning after surgery, 13 (10.9%) of hydroxyethyl starch patients and 34
      (28.8%) saline patients were using catecholamines (p = .001). Hydroxyethyl starch
      patients had less pneumonia and mediastinal infections (p = .03) and less cardiac
      pacing (p = .03). There were two deaths in each group. There was no difference in
      the daily creatinine, development of RIFLE risk criteria during hospital stay, or
      new dialysis. The numbers and volumes of packed red blood cells were similar in
      the two groups, but more hydroxyethyl starch patients received plasma
      transfusions (p = .05). CONCLUSIONS: Use of a colloid solution for volume
      resuscitation in a nurse-delivered flow-based algorithm, which included a
      pulmonary artery catheter, significantly improved hemodynamic status, an
      important factor for readiness for discharge from the intensive care unit.

PMID- 20802323
TI  - Volume of emergency department admissions for sepsis is related to inpatient
      mortality: results of a nationwide cross-sectional analysis.
AB  - OBJECTIVES: Emergency department resuscitation plays a significant role in sepsis
      care, and it is unknown if patient outcomes vary by institution based on the
      level of sepsis experience of the emergency department. This study examines
      whether there is an association between the annual volume of patients admitted
      via the emergency department with sepsis and inpatient mortality. DESIGN: Cross
      sectional analysis of the 2007 Nationwide Inpatient Sample. SETTING AND PATIENTS:
      We included 87,166 adult emergency department sepsis admissions from 551
      hospitals. MEASUREMENTS: Hospitals were categorized into quartiles by 2007
      emergency department sepsis volume. Univariate associations of patient
      characteristics, hospital characteristics, and inpatient mortality with sepsis
      volume level were evaluated by chi-square test. A population-averaged logistic
      regression model of inpatient mortality was used to estimate the effects of age,
      gender, comorbid conditions, payer status, median zip code income, hospital bed
      size, teaching status, and emergency department sepsis volume. MAIN RESULTS:
      Overall inpatient sepsis mortality was 18.0% and early mortality (2 days after
      admission) was 6.9%. The risk-adjusted odds ratios of mortality were 0.73 (95%
      confidence interval, 0.64-0.83; p < .001) in quartile 4 (highest volume), 0.83 in
      quartile 3 (95% confidence interval, 0.74-0.93; p = .001), and 0.90 in quartile 2
      (95% confidence interval, 0.82-0.99; p < .05) when compared to quartile 1 (lowest
      volume). Adjusted results were similar for early mortality: 0.69 (95% confidence
      interval, 0.61-0.76; p < .001) in quartile 4, 0.83 in quartile 3 (95% confidence
      interval, 0.74-0.93; p < .05), and 0.85 in quartile 2 (95% confidence interval,
      0.77-0.94; p < .05) when compared to quartile 1. CONCLUSIONS: After adjustment
      for comorbidity and hospital-level factors, there was a significant relationship
      between emergency department sepsis case volume and overall and early inpatient
      mortality among patients admitted through the emergency department with sepsis.
      Patients admitted to hospitals in the highest-volume quartile had 27% lower odds
      of inpatient mortality in this large heterogeneous sample.

PMID- 20802324
TI  - Cirrhotic patients in the medical intensive care unit: early prognosis and long
      term survival.
AB  - OBJECTIVES: To reassess the prognosis of patients with cirrhosis admitted to the
      intensive care unit. DESIGN: A retrospective study in a medical intensive care
      unit in a teaching hospital in France. PATIENTS: All patients with cirrhosis
      without previous liver transplantation admitted in the period from 2005 to 2008.
      INTERVENTIONS: None. MAIN RESULTS: One hundred thirty-eight patients were
      studied. Survival rates in the intensive care unit, in hospital, and at 6 months
      were 59% (95% confidence interval, 50%-67%), 46% (95% confidence interval, 38%
      54%), and 38% (95% confidence interval, 30%-47%), respectively. In-hospital
      survival rates for patients requiring vasopressors, mechanical ventilation, or
      renal replacement therapy were 20%, 33%, and 31%, respectively. On day 1,
      independent risk factors for in-hospital mortality were age, albuminemia,
      international normalized ratio, and the Sequential Organ Failure Assessment score
      computed after discarding points for hematologic failure (modified Sequential
      Organ Failure Assessment score). Liver disease severity, assessed using a
      clinical classification, did not correlate with in-hospital mortality. In
      patients still alive after 3 days, the only prognostic factor was the modified
      Sequential Organ Failure Assessment score computed after 3 days. To predict in
      hospital mortality, the modified Sequential Organ Failure Assessment score on day
      1 had a greater area under the receiver operating characteristic curve (0.84)
      than the Simplified Acute Physiology Score II (0.78), the Child-Pugh score
      (0.76), the model for end-stage liver disease score (0.77), or the model for end
      stage liver disease-natremia score (0.75). The in-hospital mortality rate with
      three or four nonhematologic organ failures on day 1 was not >70%, whereas it was
      89% with three nonhematologic organ failures after 3 days spent in the intensive
      care unit. CONCLUSION: In-hospital survival rate of intensive care unit-admitted
      cirrhotic patients seemed acceptable, even in patients requiring life-sustaining
      treatments and/or with multiple organ failure on admission. The most important
      risk factor for in-hospital mortality was the severity of nonhematologic organ
      failure, as best assessed after 3 days. A trial of unrestricted intensive care
      for a few days could be proposed for select critically ill cirrhotic patients.

PMID- 20802325
TI  - Surrogate consent for research involving adults with impaired decision making:
      survey of Institutional Review Board practices.
AB  - OBJECTIVES: Most critically ill adults have impaired decision-making capacity and
      are unable to consent to research. Yet, little is known about how Institutional
      Review Boards interpret the Common Rule's call for safeguards in research
      involving incapacitated adults. We aimed to examine Institutional Review Board
      practices on surrogate consent and other safeguards to protect incapacitated
      adults in research. DESIGN, SETTINGS, AND PARTICIPANTS: A cross-sectional survey
      of 104 Institutional Review Boards from a random sample of U.S. institutions
      engaged in adult human subject research (response rate, 68%) in 2007 and 2008.
      INTERVENTIONS: None. MEASUREMENTS: Institutional Review Board acceptance of
      surrogate consent, research risks, and other safeguards in research involving
      incapacitated adults. MAIN RESULTS: Institutional Review Boards reported that, in
      the previous year, they sometimes (49%), frequently (33%), or very frequently
      (2%) reviewed studies involving patients in the intensive care unit. Six
      Institutional Review Boards (6%) do not accept surrogate consent for research
      from any persons, and 22% of Institutional Review Boards accept only an
      authorized proxy, spouse, or parent as surrogates, excluding adult children and
      other family. Institutional Review Boards vary in their limits on research risks
      in studies involving incapacitated adults: 15% disallow any research regardless
      of risk in studies without direct benefit, whereas 39% allow only minimal risks.
      When there was potential benefit, fewer Institutional Review Boards limit the
      risk at minimal (11%; p < .001). Even in populations at high risk for impaired
      decision making, many Institutional Review Boards rarely or never required
      procedures to determine capacity (13%-21%). Institutional Review Boards also
      varied in their use of independent monitors, research proxies, and advanced
      research directives. CONCLUSIONS: Much variability exists in Institutional Review
      Board surrogate consent practices and limits on risks in studies involving
      incapacitated adults. This variability may have adverse consequences for needed
      research involving incapacitated adults. Clarification of current regulations is
      needed to provide guidance.

PMID- 20802326
TI  - The impact of Acinetobacter baumannii infections on outcome in trauma patients: a
      matched cohort study.
AB  - OBJECTIVE: To determine the impact of Acinetobacter baumannii infection on the
      outcome of trauma patients. DESIGN AND SETTING: A retrospective 1:2-matched
      cohort study. Level I trauma intensive care unit patients with confirmed
      Acinetobacter baumannii infection were defined as cases. PATIENTS: Thirty-one
      Acinetobacter baumannii patients were matched to 62 controls with evidence of
      infection caused by other microorganisms. MEASUREMENTS AND MAIN RESULTS: There
      were 12 matching criteria, including focus of infection, demographics, severity,
      and characteristics of injury. In-hospital mortality rate, intensive care unit
      length of stay, and complications of Acinetobacter baumannii including multidrug
      resistant strains in patients were compared to those of their controls; 81% had
      hospital-acquired pneumonia, 13% had bloodstream infections, and 6% had urinary
      tract infections in both groups. Acinetobacter baumannii cultures were multidrug
      resistant in 42% (13/31) of cases. The initial empirical antibiotic therapy was
      adequate in 71% (22/31). Although the in-hospital mortality was higher in the
      Acinetobacter baumannii group (16% vs. 13%; odds ratio, 1.23; 95% confidence
      interval, 0.38-4.36; p = .67), the difference did not reach statistical
      significance. Using the test of equivalence or clinical indifference, the impact
      of an Acinetobacter baumannii infection on mortality is inconclusive. This
      applies also to multidrug-resistant strains. Overall intensive care unit stay was
      prolonged for Acinetobacter baumannii when compared to controls (median, [range],
      28 [7-181] days vs. 17 [2-130] days, respectively; p = .05). ARDS and acute liver
      failure were more frequent in the Acinetobacter baumannii group compared to the
      control group (35% vs. 15%; odds ratio, 3.24; 95% confidence interval, 1.17-5.48;
      p = .02 and 26% vs. 10%; odds ratio, 3.25; 95% confidence interval, 3.25-10.40; p
      = .04). CONCLUSIONS: In this single-center experience, Acinetobacter baumannii
      infection, including multidrug-resistant strains, has inconclusive impact on
      mortality in a cohort of trauma patients. Larger studies are needed to support a
      definite conclusion. Acinetobacter baumannii infection was, however, associated
      with a longer intensive care unit stay and a higher rate of organ failure.

PMID- 20802327
TI  - Ischemic optic neuropathy: are we any further?
AB  - PURPOSE OF REVIEW: Postoperative vision loss (POVL) as related to spinal surgery
      and the prone position has garnered increasing attention in the US over the last
      15 years, resulting in an increase of litigations submitted to the legal system.
      It might be associated with the development of new surgical techniques involving
      complex instrumentation of the spine. By 2000, the magnitude of this problem was
      such that the American Society of Anesthesiologists developed a Postoperative
      Visual Loss Registry in an effort to better understand and evaluate this
      devastating operative complication. RECENT FINDINGS: The cause of ischemic optic
      neuropathy (ION) as the most complex entity of POVL is still unclear.
      Retrospective studies show that although it can strike patients of any age, there
      is an increased incidence in patients less than 18 and more than 65 years of age.
      Significant risk factors include male sex, anemia, surgery lasting over 6 h, and
      intraoperative hypotension. Profound anatomical knowledge and new animal studies
      have helped to define possible mechanisms underlying ION. SUMMARY: ION is still
      poorly understood and risk factors remain speculative. Given that there is no
      known treatment, increased understanding should help to prevent this
      postoperative complication.

PMID- 20802328
TI  - Thoracic endovascular stent-graft therapy in aortic dissection.
AB  - PURPOSE OF REVIEW: Aortic dissection is an uncommon but highly lethal condition
      with a mortality rate of 1-2% per hour within the first 24 h when the ascending
      aorta is affected and remains a surgical domain. For the treatment of type B
      aortic dissection, however, endovascular techniques became available recently and
      are increasingly popular. This review focuses on current indications and results
      of thoracic endovascular stent-graft therapy in aortic dissection. RECENT
      FINDINGS: Uncomplicated type B aortic dissections should be managed medically and
      kept under surveillance for delayed expansion in 20-50% patients over 4 years.
      Endovascular treatment should be considered in the setting of impending or actual
      complications, for example, when the aortic diameter exceeds 55-60 mm, in the
      case of uncontrolled pain or blood pressure with evidence of malperfusion
      syndrome or rapid growth of the dissecting aneurysm (>1 cm/year). In both
      complicated acute and chronic type B aortic dissections, endovascular therapy may
      emerge as an attractive alternative to open surgery. However, in uncomplicated
      chronic type B aortic dissection, endovascular therapy failed to improve outcomes
      over optimal medical therapy within 2 years despite aortic remodeling. SUMMARY:
      Endovascular stent-graft therapy for aortic dissection is emerging with good mid
      term results. Further indications, that is, aortic arch dissection and
      uncomplicated acute aortic dissections, are under evaluation.

PMID- 20802329
TI  - Emerging antithrombotic agents: what does the intensivist need to know?
AB  - PURPOSE OF REVIEW: As thrombus consists of both fibrin and platelets,
      antithrombotic strategies involve anticoagulants and antiplatelets, alone or in
      combination. RECENT FINDINGS: Traditionally, unfractionated heparin has been the
      most commonly used parenteral anticoagulant, but owing to its variable dose
      response and narrow therapeutic indices, it is being replaced by low molecular
      weight heparin, fondaparinux, and bivalrudin. New oral factor Xa inhibitors like
      apixaban and rivaroxaban are still on the horizon, awaiting definite evaluation
      in ACS, DVT and atrial fibrillation. On the contrary, a dramatic advance in the
      arena of oral anticoagulants has occurred with the introduction of dabigatran, an
      oral direct thrombin inhibitor. This agent showed better outcomes than oral
      vitamin K antagonists in patients with atrial fibrillation. The antiplatelet
      field has also expanded by the addition of two new agents, prasugrel and
      ticagrelor. These agents have been tested against clopidogrel, in patients with
      ACS, with superior efficacy outcomes for both agents and higher bleeding events
      with prasugrel. SUMMARY: Bleeding risk associated with antithrombotics is not
      only a function of their inherent biochemical properties but also a reflection of
      how healthcare professionals choose and dose these agents in individual patients.

PMID- 20802330
TI  - Adverse effects of proton pump inhibitor drugs: clues and conclusions.
AB  - PURPOSE OF REVIEW: To review evidence relating to the strength of associations
      that have appeared in largely observational studies, between high-dose or long
      term use of proton pump inhibitor drugs and certain possibly attributable side
      effects, which emerge from studies confounded by other variables. In
      retrospective studies not designed to assess safety, evidence of causality is
      generally lacking. RECENT FINDINGS: The associations of fractures of hip, wrist,
      forearm and other sites appear weak and only slightly higher than the risks in
      control populations matched for age. They may increase with drug exposure, but
      probably do so only in individuals in whom other risk factors are also
      operational (smoking, alcohol, poor nutrition, steroids, etc.). The risks of
      Clostridium difficile colitis, other enteric infections, small bowel bacterial
      overgrowth and possibly spontaneous bacterial peritonitis also appear increased.
      Impaired gastric secretion may adversely affect the absorption of various
      nutrients, but their clinical impact is ill defined. Potentially more important
      are the consequences of hypergastrinemia, including rebound hypersecretion of
      acid, and possible development of various cancers, including carcinoid tumors.
      Effects of other drugs, including clopidogrel, on metabolism are reviewed, but
      clouded by uncertainties. SUMMARY: The safety of long-term PPI administration
      needs serious prospective study.

PMID- 20802331
TI  - Multiresistant Gram-negative infections: a global perspective.
AB  - PURPOSE OF REVIEW: Multiresistant Gram-negative infections are an increasing
      problem in hospitals and healthcare facilities worldwide. While much attention
      has been paid to Gram-positive pathogens such as methicillin-resistant
      Staphylococcus aureus and vancomycin-resistant Enterococcus lately, the
      importance of Gram-negative nosocomial infections has also been recognized
      globally. RECENT FINDINGS: Recent reports have described the spread of
      carbapenemase-producing Klebsiella pneumoniae across North America. In addition,
      many strains of Pseudomonas and Acinetobacter in Asia are resistant to all known
      antibiotics. The global epidemiology of multiresistant Gram-negative pathogens
      seems to vary by continent. There are very few existing agents which can be used
      for these pathogens and there are limited options on the horizon. This limited
      therapeutic armamentarium has been an impetus for novel approaches including
      combination therapies and increased attention to infection control and prevention
      efforts. SUMMARY: Clinicians need to be aware of the rising problem of resistance
      in nosocomial and community-acquired Gram-negative pathogens. Novel agents are
      urgently needed to combat these infections and innovative infection control
      strategies need to be devised to protect our vulnerable patients.

PMID- 20802332
TI  - Amebic meningoencephalitides and keratitis: challenges in diagnosis and
      treatment.
AB  - PURPOSE OF REVIEW: Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria
      fowleri, although free-living amebae, also cause devastating diseases in humans
      leading to death. Acanthamoeba spp. and B. mandrillaris cause granulomatous
      amebic encephalitis, cutaneous and nasopharyngeal as well as disseminated
      infection. Acanthamoeba also causes a vision-threatening infection of the cornea,
      Acanthamoeba keratitis, principally in contact lens wearers. N. fowleri causes an
      acute, fulminating infection of the central nervous system, primary amebic
      meningoencephalitis, in healthy children and young adults who indulge in aquatic
      activities in fresh water. This review focuses on the recent developments in the
      diagnosis and treatment and clinical management of the diseases caused by these
      amebae. RECENT FINDINGS: Development of a multiplex real-time PCR test has made
      it possible to simultaneously detect all the three free-living amebae in a
      sample. It is a rapid assay with a short turn-around time of just 4-5 h. An early
      diagnosis would be helpful in initiating potentially effective treatment. A
      recent study reported exciting results indicating that loading of rokitamycin in
      chitosan microspheres improves and prolongs the in-vitro anti-Acanthamoeba
      activity of the drug. SUMMARY: Diagnoses of these infections are challenging and
      antimicrobial therapy is empirical, which often results in fatalities. Further
      research is needed to explore the possibility of a better drug delivery system
      that crosses the blood-brain barrier and effectively reach the central nervous
      system.

PMID- 20802333
TI  - Albuminuria: all you need to predict outcomes in chronic kidney disease?
AB  - PURPOSE OF REVIEW: Screening for chronic kidney disease frequently starts with
      assessment of estimated glomerular filtration rate (eGFR). In current approaches,
      further evaluation will only include measurement of albuminuria in case of eGFR
      less than 60 ml/min/1.73 m. We will review whether this screening approach is
      correct. RECENT FINDINGS: Albuminuria is an important predictor of both
      cardiovascular and kidney outcomes in chronic kidney disease. The predictive
      value of albuminuria for these endpoints is not only independent of well known
      risk factors, including diabetes and hypertension, but it is also independent of
      eGFR. Many individuals with normal eGFR have albuminuria. More research is needed
      to define why albuminuria adds to eGFR in predicting outcomes. After leakage
      through the glomerular filter, albumin is not only excreted in urine, but also
      reabsorbed by tubules. Albuminuria may, therefore, be a marker of both glomerular
      and tubular damage, whereas eGFR is merely a marker of glomerular damage.
      SUMMARY: As many individuals with an eGFR more than 60 ml/min/1.73 m have
      microalbuminuria, and albuminuria is an independent predictor of both renal and
      cardiovascular outcomes, screening for chronic kidney disease should at least
      include measurement of albuminuria. Future studies should consider whether the
      inclusion of (other) markers of tubular damage will further improve our ability
      to predict outcomes in patients with chronic kidney disease.

PMID- 20802334
TI  - Structure and function of cochlear afferent innervation.
AB  - PURPOSE OF REVIEW: For the perception of sound, acoustic signals need to be
      encoded into a neuronal code. This takes place at the inner hair cells of the
      organ of Corti and the afferent fibres of the auditory nerve. We will review the
      current knowledge of the anatomy and function of these elements as well as their
      connection - formed by the afferent inner hair cell synapse. RECENT FINDINGS:
      Depending on their tonotopic location, inner hair cells are innervated by 5-30
      dendrites of spiral ganglion neurons. Electrophysiological recordings from single
      fibres demonstrate - apart from a high-frequency selectivity - a pronounced
      heterogeneity in their response to sound of varying intensity. The source as well
      as the function of this heterogeneity is not well understood, but recent
      publications have suggested several mechanisms, including variations in the
      presynaptic Ca2+ influx and subsequent transmitter release, the postsynaptic
      sensitivity to neurotransmitter and electrical as well as anatomical variability
      of single fibres. These mechanisms might act together to expand the dynamic range
      of sound that can be encoded. SUMMARY: Classical studies as well as recent
      publications demonstrate that sound encoding at the inner hair cell afferent
      synapse involves mechanisms leading to tonotopic frequency separation and
      distribution of intensity coding over many neuronal channels.

PMID- 20802335
TI  - Psychopharmacologic treatment of traumatized youth.
AB  - PURPOSE OF REVIEW: To review and summarize existing literature regarding
      pharmacological interventions for post-traumatic stress disorder (PTSD) in
      children and adolescents. A literature search limited to articles focused on the
      pharmacological treatment of children aged 0-18 years with a history of trauma
      and/or PTSD was conducted through the National Library of Medicine and PsychInfo,
      1967-present, and each citation manually reviewed. RECENT FINDINGS: Pharmacologic
      trials for pediatric PTSD are limited in scope and number, with one small double
      blind, randomized controlled trial of the selective serotonin reuptake inhibitor
      (SSRI) sertraline. Two brief, small, double-blind, randomized controlled trials
      of imipramine for children and adolescents with acute stress disorder have been
      conducted, with mixed results. Only case reports or open-labeled trials have been
      conducted with alpha-adrenergic agents, other antidepressants, atypical
      antipsychotics, and antiepileptic agents. SUMMARY: Data supporting the use of
      medications in the treatment of PTSD in children and adolescents are limited.
      SSRIs show promise and deserve additional study, but conclusive support for their
      use is not available as it is in adults. Additional research is needed, with
      other drugs of interest including other antidepressants, alpha-adrenergic agents,
      and possibly the antiepileptic agent carbamazepine.

PMID- 20802336
TI  - The history of 'Female Sexual Dysfunction' as a mental disorder in the 20th
      century.
AB  - PURPOSE OF REVIEW: To provide an overview of conceptualizations of female sexual
      problems, and 'Female Sexual Dysfunction' in particular, throughout the 20th
      century, especially in relation to psychiatry and mental illness. RECENT
      FINDINGS: In the past 15 years, there has been an increase in both medical and
      public discourse about 'Female Sexual Dysfunction'. I discuss a variety of
      literature sources dealing with female sexual problems, where these are
      understood variously as problems of developmental psychopathology, as technical
      phenomena to be resolved through education, or as medical problems to be
      addressed pharmaceutically. SUMMARY: The stigma of mental illness shapes much
      recent discussion of female sexual problems, as does the legacy of the postwar
      critique of psychodynamic psychiatry.

PMID- 20802337
TI  - Parenteral nutrition in patients with cancer: recent guidelines and a need for
      further study.
AB  - PURPOSE OF REVIEW: This review is intended to summarize previous data on the use
      of parenteral nutrition in cancer patients to acknowledge recent guidelines on
      this subject and to suggest a need for further research. RECENT FINDINGS: Recent
      guidelines advise against parenteral nutrition in patients with incurable
      malignancies, although in some situations, patients with locally advanced cancers
      - not necessarily incurable cancers - might derive some benefit. Further study is
      indicated to better understand if other subgroups of patients might derive
      benefit and to understand quality of life issues. SUMMARY: Recent guidelines are
      of value in clinical management but there remains a need to further study the
      role of parenteral nutrition in cancer patients.

PMID- 20802338
TI  - Prospective study of alcohol use and hearing loss in men.
AB  - OBJECTIVE: Hearing loss is a common and disabling sensory disorder, yet
      prospective data on potentially modifiable risk factors are limited. Previous
      studies suggest that alcohol consumption may influence the development of hearing
      loss, yet results have been inconsistent. The purpose of this study was to
      prospectively examine the relation between alcohol use and hearing loss in men.
      DESIGN: We examined prospectively the independent association between alcohol
      intake and self-reported professionally diagnosed hearing loss in 26,809 men aged
      40 to 74 yrs at baseline in 1986. Study participants completed detailed
      questionnaires at baseline and every 2 yrs thereafter. Incident cases of hearing
      loss were defined as those professionally diagnosed after 1986. Cox proportional
      hazards multivariate regression was used to adjust for potential confounding
      factors. RESULTS: During 386,081 person-years of follow-up, 3447 incident cases
      of hearing loss were reported. Overall, there was no association between level of
      alcohol intake and risk of hearing loss. Compared with those who did not consume
      alcohol, the multivariate-adjusted hazard ratios (95% confidence interval) were
      1.00 (0.89 to 1.12) for those who consumed 5.0 to 9.9 g/day, 1.08 (0.96 to 1.21)
      for 10.0 to 14.9 g/day, and 0.98 (0.85 to 1.13) for 30.0 to 49.9 g/day. The
      results did not differ by age group or folate intake. Among those with lower
      intake of vitamin B12, however, higher consumption of alcohol, specifically
      liquor, was associated with an increased risk of hearing loss. CONCLUSIONS: Our
      data suggest that low or moderate alcohol consumption does not influence the risk
      of hearing loss in older men. A possible relation between vitamin B12 intake,
      alcohol consumption, and hearing loss merits further investigation.

PMID- 20802340
TI  - Effects of recognizing depression with a standardized questionnaire (CES-D)
      versus patient reporting of depression after a single-standardized question on
      the outcomes of treatment for hepatitis C with pegylated interferon-alpha-2b and
      ribavirin.
AB  - BACKGROUND: Depression may worsen during antiviral treatment for hepatitis C
      virus, resulting in noncompliance treatment. AIM: The aim was to compare the
      response and compliance rates between the groups of veteran patients using two
      different methods of identifying depression, either the Centers for Epidemiology
      Studies for Depression Scale (group A) questionnaire or the report of symptoms of
      depression after a single-standardized question by the health care provider
      (group B). METHODS: One hundred and twenty-nine patients were randomly assigned
      to the two groups before the treatment. RESULTS: No statistical differences were
      noted in baseline characteristics between the groups. Depression was common in
      both the groups. No difference between initial Centers for Epidemiologic Studies
      Depression Scale scores and diagnosis of depression between the two groups was
      noted. Furthermore, the number of patients diagnosed with depression during the
      treatment was similar in each group. There were no significant differences
      between the groups in rates of sustained viral response (30% group A, 35% group
      B) or in rates of overall compliance with patients receiving more than 90% of
      prescribed PegIntronA therapy (44% group A, 39% group B), and ribavirin (32%
      group A and 37% group B). CONCLUSION: The use of the Centers for Epidemiology
      Studies for Depression Scale questionnaire to recognize depression had no
      significant advantage over patient reporting of depression symptoms after a
      single-standardized question on the hepatitis C virus clearance and the treatment
      compliance rates in veteran populations.

PMID- 20802339
TI  - The effect of alcohol, tobacco and caffeine consumption and vegetarian diet on
      gallstone prevalence.
AB  - AIM: To investigate the effects of alcohol, tobacco and caffeine consumption and
      of vegetarian diet on gallstone prevalence in an urban population sample.
      METHODS: A total of 2417 individuals underwent ultrasound examination and
      completed a standardized questionnaire as part of the EMIL study. Statistical
      analysis of the data considered the known risk factors of age, female sex, BMI,
      positive family history and potential confounders, such as alcohol, caffeine and
      tobacco consumption and vegetarian diet using multiple logistic regression with
      variable selection. RESULTS: The prevalence of gallstones in the population
      sample was 8% (171 out of 2147). Findings of the study confirmed the classic risk
      factors of age, female sex, obesity and positive family history. After the
      variable selection of potential risk factors in a logistic regression that was
      adjusted for age, female sex, BMI and positive family history, the factors like
      tobacco [odds ratio (OR) 1.09, 95% confidence interval (CI): 0.76-1.56, P=0.64]
      and caffeine consumption (OR: 0.77, 95% CI: 0.42-1.42, P=0.40) as well as
      vegetarian diet (OR: 1.14, 95% CI: 0.39-3.35, P=0.81) had no effect on gallstone
      prevalence. A protective effect against development of gallstones was shown for
      alcohol consumption (OR: 0.67, 95% CI: 0.46-0.99, P=0.04). CONCLUSION: The
      factors like tobacco and caffeine consumption as well as vegetarian diet exerted
      no measurable effect on the prevalence of gallstones. A protective effect was
      found for alcohol consumption.

PMID- 20802341
TI  - Cost-effectiveness of colorectal cancer screening with computed tomography
      colonography or fecal blood tests.
AB  - OBJECTIVE: To assess the cost-effectiveness of colorectal cancer screening using
      computed tomography colonography (CTC) and immunological fecal occult blood test
      (iFOBT). METHODS: CTC and iFOBT strategies were compared with Nn screening or
      guaiac FOBT (gFOBT) using Markov modeling. CTC was proposed at 50, 60, and 70
      years, whereas gFOBT and iFOBT were performed every 2 years beginning at 50 years
      until 74 years of age with a 30-year time horizon. We calculated incremental cost
      effectiveness ratios and efficiency ratios (ERs). Then, we performed univariate
      and probabilistic sensitivity analyses. RESULTS: With gFOBT as reference,
      colorectal cancer prevention rate was 18% for CTC and 11% for iFOBT. The
      incremental cost-effectiveness ratio of CTC and iFOBT were respectively 3204 and
      5458 euro per life years gained (LYG), the ER for CTC was 0.22 and the ER for
      iFOBT was 2.08 colonoscopies per LYG. Cost-effectiveness results were sensitive
      to CTC cost. In the probabilistic sensitivity analysis, compared with CTC, iFOBT
      strategy was cost-effective for 84.6% of simulations when we assumed a
      willingness to pay (WTP) of 20,000 euro/LYG. CONCLUSION: CTC requires
      substantially less colonoscopies than iFOBT and is cost-effective for low values
      of WTP. However, iFOBT is the preferred screening strategy for a WTP greater than
      6207 euro/LYG.

PMID- 20802342
TI  - Coffee and the liver: a potential treatment for liver disease?
AB  - Liver disease is the fifth commonest cause of death in the UK. Observational and
      case-controlled studies have suggested that coffee is beneficial in liver
      disease, but this evidence has yet to be evaluated or placed into the context of
      the natural history of liver disease. The aim of this study was to review the
      current evidence for the role of coffee in liver disease. Several studies
      consistently show that coffee drinkers have a reduced risk of abnormal liver
      function tests, cirrhosis and hepatocellular carcinoma. There is a clear dose
      response to this benefit. As the effect of this widely available food substance
      seems substantial further data, ideally from an interventional study of coffee in
      patients with liver disease, is urgently required particularly because of the
      potential to reduce fibrosis and hepatocellular carcinoma risk. This would be the
      first intervention of its kind to have proven benefit irrespective of etiology of
      liver disease.

PMID- 20802343
TI  - Sexual transmission risk behavior of adolescents With HIV acquired perinatally or
      through risky behaviors.
AB  - OBJECTIVE: To describe the prevalence and predictors of the transmission-related
      behaviors of adolescents with HIV acquired perinatally (perinatal) or through
      risky behaviors (behavioral). METHODS: HIV-positive adolescents (n = 166) aged 13
      21, receiving care in 3 US cities, reported sexual behaviors, drug use, and
      psychosocial and demographic characteristics. HIV-related data were abstracted
      from medical records. RESULTS: Of 105 sexually experienced adolescents reporting
      risk history (42 perinatal, 63 behavioral), 49 had engaged in unprotected sex
      since learning their diagnosis (12 perinatal, 37 behavioral). Of sexually
      experienced girls, 19 had been pregnant (5 of 24 perinatal, 14 of 31 behavioral).
      Risk information was provided for 115 of 132 recent sex partners, 61 of whom had
      unprotected sex with study participants (10 with 8 perinatal participants; 51
      with 33 behavioral participants). Recent unprotected sex was associated with
      sexual abuse during adolescence (adjusted odds ratio = 9.61, 95% CI: 1.07 to
      86.12) and greater HIV knowledge (adjusted odds ratio = 1.29, 95% CI: 1.00 to
      1.66) when transmission category, age, and sexual orientation were controlled.
      CONCLUSIONS: To limit HIV transmission and prevent unplanned pregnancies,
      developmentally appropriate risk-reduction interventions, and screening and
      treatment referral for sexual abuse, must be integrated into the care of both
      perinatally and behaviorally HIV-infected adolescents.

PMID- 20802344
TI  - Extraskeletal osteochondroma near the hip: a pediatric case.
AB  - Extraskeletal osteochondroma near the hip is rare and its pathological diagnosis
      is based on radiological and histopathological examination. It is vital that such
      a diagnosis be considered when a discrete, ossified mass is localized in soft
      tissues, even at atypical sites. Differential diagnoses include myositis
      ossificans, a lipomatous lesion, a pseudomalignant osseous tumour, an ossifying
      fibromyxoid tumour, an extraskeletal chondroma with endochondral ossification,
      synovial (osteo) chondromatosis, tumoural calcinosis, a synovial sarcoma and an
      extraskeletal osteosarcoma. Clinical awareness of this benign entity is important
      as no malignant transformation or metastasis has been reported. Marginal excision
      with histopathological identification is the treatment of choice.

PMID- 20802345
TI  - A systematic review of extrapleural pneumonectomy for malignant pleural
      mesothelioma.
AB  - INTRODUCTION: The primary objective of the present systematic review was to
      evaluate the safety and efficacy of extrapleural pneumonectomy (EPP) for patients
      with malignant pleural mesothelioma. METHODS: A systematic review of relevant
      studies identified through five online search databases was performed. Two
      reviewers independently appraised each study. RESULTS: Thirty-four of 58 relevant
      studies from 26 institutions containing the most updated data were evaluated for
      survival and perioperative outcomes after EPP. The median overall survival varied
      from 9.4 to 27.5 months, and 1-, 2-, and 5-year survival rates ranged from 36 to
      83%, 5 to 59%, and 0 to 24%, respectively. Overall perioperative mortality rates
      ranged from 0 to 11.8%, and the perioperative morbidity rates ranged from 22 to
      82%. Quality of life assessments from three studies reported improvements in
      nearly all domains at 3 months postoperatively. Patients who underwent
      trimodality therapy involving EPP and adjuvant chemoradiotherapy had a median
      overall survival of 13 to 23.9 months. DISCUSSIONS: The current evidence suggests
      that selected patients with malignant pleural mesothelioma may benefit from EPP,
      especially when combined with neoadjuvant or adjuvant chemotherapy and adjuvant
      radiotherapy.

PMID- 20802346
TI  - Prognostic impact of node involvement pattern in pN1 non-small cell lung cancer
      patients.
AB  - INTRODUCTION: We previously showed that squamous cell carcinoma (SCC) patients
      with directly involved N1 nodes resulted in outcomes significantly better than
      those with separately involved N1 nodes. The purpose of this study was to
      evaluate the prognostic effect of node involvement patterns in pN1 non-small cell
      lung cancer (NSCLC) patients, with special attention given to any differences
      between SCC and adenocarcinoma (AD). METHODS: We reviewed 324 consecutive
      patients with completely resected pN1 NSCLC and classified them into two groups
      based on their node involvement patterns: directly or separately involved N1
      groups. To compare survival rates, 1545 pN0 patients and 330 pN2 patients were
      also investigated. RESULTS: Univariate and multivariate analyses showed that the
      node involvement pattern was significantly associated with pN1 NSCLC patient
      outcome. The directly involved N1 group had a much better 5-year overall survival
      rate of 60.1% compared with 45.0% for the separately involved N1 group. In SCC
      patients, the directly involved N1 group showed an overall survival similar to
      pN0 patients, whereas overall survival of the separately involved N1 group was
      identical to that of pN2 patients, and their survival rates were significantly
      different. In AD patients, however, the survival rates were marginally different
      between the directly and separately involved N1 groups, and they were
      intermediate between pN0 and pN2 patient survival rates. CONCLUSIONS: Node
      involvement patterns had significant prognostic effect in pN1 NSCLC patients.
      This effect was different between SCC and AD cases. The subclassification of N1
      based on node involvement pattern is of significance for SCC patients but not for
      AD patients.

PMID- 20802347
TI  - Tumor invasion of extralobar soft tissue beyond the hilar region does not affect
      the prognosis of surgically resected lung cancer patients.
AB  - INTRODUCTION: Visceral pleural invasion, which is defined as tumor extension
      beyond the elastic lamina, is one of the most important prognostic factors in
      patients who have undergone curative resection for non-small cell lung cancer.
      However, in pathologic slides, pleural elastic lamina could not be found in the
      hilar region in which the pleura is reflected. Till date, when cancer cells are
      seen in this region, a basical agreement dealing with T factor is controversial
      among pathologists. The purpose of this study is to evaluate the significance of
      tumor invasion of that region as a prognostic factor. METHODS: We reviewed 91
      cases of surgically resected lung cancer in which invasion of the hilar region
      was visible macroscopically. By microscopic examination, we divided them into
      three groups: a group in which no cancer cells are seen in the soft tissue beyond
      the hilar region (group A), a group in which cancer cells are seen in the soft
      tissue beyond the hilar region (group B), and a group in which cancer cells could
      not be seen in the soft tissue beyond the hilar region but invade into the
      mediastinal visceral pleura at some other site (group C). We then evaluated the
      clinicopathologic characteristics of the patients and their outcome. RESULTS:
      There was no statistically significant difference in the 5-year overall survival
      rate or disease-free survival rate between group A and group B (overall: 55
      versus 48%; disease free: 43 versus 42%), but disease-free survival of group C
      was significantly lesser than that of group A and group B (A versus C: p = 0.022;
      B versus C: p = 0.040). CONCLUSION: Tumor invasion of the soft tissue beyond
      hilar region would not be a prognostic factor in patients who have undergone
      curative resection for primary lung cancer, although investigation of larger
      number of cases will be needed to confirm the validity of our conclusion.

PMID- 20802348
TI  - Stromal macrophage expressing CD204 is associated with tumor aggressiveness in
      lung adenocarcinoma.
AB  - BACKGROUND: Tumor tissue is composed of variable numbers of cancer cells and
      stromal cells, and tumor-associated macrophages are recruited into cancer-induced
      stroma and produce a specific microenvironment. Alternatively, activated
      macrophages (M2 phenotype) are known to be related to tumor progression and
      outcome, and CD204 has been reported to be expressed in M2 macrophages in some
      tumors. METHODS: To investigate whether CD204-positive macrophages reflect tumor
      aggressiveness in adenocarcinoma of the lung, we investigated the relationships
      between the numbers of CD204-positive stromal macrophages and both
      clinicopathological features and outcome in 170 consecutive resected cases. We
      also examined the relationships between the numbers of CD204-positive macrophages
      and the expression levels of cytokines involved in the migration and
      differentiation of M2 macrophages. RESULTS: The numbers of CD204-positive
      macrophages were significantly correlated with several prognostic factors. The
      log-rank test showed a significant association between the numbers of CD204
      positive macrophages and a poor outcome (p = 0.0073), whereas the numbers of
      macrophages expressing CD68, a pan-macrophage/monocyte marker, were of marginal
      prognostic significance (p = 0.0789). We evaluated associations between the
      levels of expression of the cytokines IL-6, IL-10, IL-12a, IL-12b, M-colony
      stimulating factor, IFN-gamma-., and monocyte chemoattractant protein-1 in cancer
      tissue and the numbers of CD204-positive macrophages. The expression levels of IL
      10 and monocyte chemoattractant protein-1, which are involved in differentiation,
      accumulation, and migration of M2 macrophages, were significantly correlated with
      the numbers of CD204-positive macrophages (p = 0.031 and p = 0.031,
      respectively). CONCLUSION: These findings demonstrated that CD204-positive
      macrophages clearly reflect the tumor-promoting phenotype of tumor-associated
      macrophages in lung adenocarcinoma.

PMID- 20802349
TI  - Clinical significance of epidermal growth factor receptors in non-small cell lung
      cancer and a prognostic role for HER2 gene copy number in female patients.
AB  - INTRODUCTION: To compare the efficacy of silver in situ hybridization (SISH) and
      immunohistochemistry (IHC) in detecting HER2 alterations and to investigate the
      prevalence and prognostic significance of Erb family members in non-small cell
      lung cancer (NSCLC). METHODS: Stage I to IIIA tumors from 335 patients with NSCLC
      were immunohistochemically tested for protein expression of all Erb family
      members. Membranous HER2 expression was compared with its gene copy number by
      SISH in paraffin-embedded, formalin-fixed material. Correlations were made with
      clinicopathological variables. RESULTS: Synchronous high immunohistochemical
      expression of all Erb family members was seen in 8% of tumor samples. There was a
      significant correlation between the HER2 gene copy number and HER2 protein
      expression (p = 0.003). High nuclear HER3 expression correlated significantly
      with high HER2 gene copy numbers (p = 0.015). In univariate analyses, high HER2
      gene copy number was a highly significant negative prognostic indicator for
      disease-specific survival in women (p = 0.005), whereas it did not show
      prognostic influence in men (p = 0.9). Neither polysomy of chromosome 17 nor the
      IHC expression of Erb family member proteins as singles or pairs correlated
      significantly with survival. In the multivariate analysis, high HER2 gene copy
      number in tumor epithelial cells (p = 0.03) was an independent prognostic factor
      for disease-specific survival in female patients. CONCLUSIONS: IHC does not
      consistently identify patients likely to have a poor prognosis, whereas SISH
      provides superior prognostic information for female patients with NSCLC. High
      HER2 gene copy number in tumor epithelial cells is an independent predictor of
      inferior survival in female patients with primary NSCLC.

PMID- 20802350
TI  - Prognostic factors for survival after surgical palliation of malignant pleural
      effusion.
AB  - INTRODUCTION: To investigate prognostic factors for patient survival after
      surgical palliation of malignant pleural effusion (MPE). METHOD: We reviewed 278
      consecutive nonoverseas patients (108 men, median age: 60 years [range 26-89])
      undergoing 310 surgical procedures for palliation of MPE over a 72-month period.
      There were 195 thoracoscopic talc pleurodesis, 39 pleuroperitoneal shunts, 38
      pleurodesis by an intercostal drain, 29 pleural biopsies alone, and nine long
      term drains. Referring physicians provided survival data. The significance of
      prognostic factors was examined with the log-rank test (Kaplan-Meier), those
      significant entered a Cox logistic multivariate regression analysis. RESULTS:
      Follow-up was complete until death (following 264 procedures) and for a median
      648 days (range 173-2135) for surviving patients. Overall median postoperative
      survival was 211 days (95% confidence interval: 169-253). Survival was not
      significantly different for tumor type or method of palliation. In univarate
      analysis, preoperative leucocytosis, hypoxemia, raised alanine transaminase, body
      mass index below 18 and hypoalbuminemia were associated with a significantly
      reduced postoperative survival. In multivariate analysis, leucocytosis (p <
      0.0001), hypoxemia (p = 0.014), and hypoalbuminemia (p < 0.0001) maintained
      significance. CONCLUSIONS: The survival reported demonstrates the necessity of an
      active approach to palliation of MPE. The identification of prognostic factors
      will assist the choice of palliative technique. In addition, an appreciation of
      the influence of selection on survival after surgical palliation of malignant
      pleural mesothelioma, especially that of unforeseen prognostic factors, is useful
      when evaluating the results of aggressive treatment such as chemoradiotherapy and
      radical surgery for these diseases.

PMID- 20802351
TI  - A phase II, open-label, randomized study to assess the efficacy and safety of
      AZD6244 (ARRY-142886) versus pemetrexed in patients with non-small cell lung
      cancer who have failed one or two prior chemotherapeutic regimens.
AB  - INTRODUCTION: AZD6244 (ARRY-142886) is a potent, selective MEK inhibitor. This
      study aimed to evaluate the efficacy and safety of AZD6244 versus pemetrexed as
      second- or third-line treatment in patients with advanced non-small cell lung
      cancer (NSCLC). METHODS: In this randomized phase II study, patients received
      either 100 mg oral AZD6244 free-base suspension twice daily or 500 mg/m(2)
      intravenous pemetrexed once every 3 weeks after pretreatment with a
      corticosteroid, folic acid, and vitamin B12. The primary end point of the study
      was the disease progression event count. RESULTS: Eighty-four patients were
      randomized. Disease progression events were experienced by 28 (70%) and 26 (59%)
      patients in the AZD6244 and pemetrexed groups, respectively. Median progression
      free survival was not statistically significantly different between the AZD6244
      and pemetrexed groups (67 versus 90 days, respectively; hazard ratio 1.08, two
      sided 80% confidence interval = 0.75-1.54; p = 0.79). Two patients in the AZD6244
      group had a best response to treatment of partial response. In the pemetrexed
      group, one patient achieved a complete response and one patient a partial
      response. Dermatitis acneiform, diarrhea, nausea, and vomiting were the most
      frequently reported adverse events with AZD6244, compared with fatigue, anemia,
      nausea, anorexia, and dermatitis acneiform with pemetrexed. CONCLUSIONS: Oral
      AZD6244 showed clinical activity as second- or third-line therapy for patients
      with advanced NSCLC. In an unselected NSCLC population, there is no suggestion
      that AZD6244 monotherapy offers any advantage over standard treatment with
      pemetrexed. Based on preclinical data and recent clinical observations, further
      development of AZD6244 in NSCLC should focus on BRAF or RAS mutation-positive
      patients and/or AZD6244-based combination regimens.

PMID- 20802352
TI  - LungPoint--a new approach to peripheral lesions.
AB  - INTRODUCTION: Although flexible bronchoscopy is the least invasive procedure for
      sampling, it is limited by its inability to reach lesions in the peripheral
      segments of the lung. Biopsy success is further compromised if the lesion is less
      than 30 mm in diameter or cannot be seen on fluoroscopy. We wanted to explore
      whether a new bronchoscopic navigation system could help access the peripheral
      lung airways and enable lesion sampling. METHODS: The LungPoint system produced a
      virtual bronchoscopic pathway indicating the bronchus into which the bronchoscope
      should be advanced. Virtual bronchoscopic images were displayed alongside and
      registered with actual bronchoscopic video. After performing broncoscopy with a
      standard bronchoscope for first examination, the thin bronchoscope was advanced
      to the target bronchus under direct visualization without fluoroscopy. A pilot
      study included consecutive patients at a tertiary teaching hospital with
      pulmonary peripheral lesions (<42 mm). Biopsies were taken later. RESULTS: Study
      subjects included 25 patients (9 women and 16 men, mean age 67 years) with 25
      lesions (mean size 28 mm). Using this navigation system, the bronchoscope could
      be advanced along the planned route in all cases. In 14 of the cases (56%), the
      bronchoscope could be advanced all the way to the lesion bronchus. The planning
      time was a median of 5 minutes, and the median examination time was 15 minutes. A
      definitive diagnosis was possible in 20 cases (80%). One patient experienced a
      small pneumothorax because of the biopsy that resolved without drainage. No other
      complications occurred. CONCLUSIONS: This navigation system is useful for
      bronchoscopy for pulmonary peripheral lesions (NCT01067755).

PMID- 20802353
TI  - Increased cortical expression of an RNA editing enzyme occurs in major depressive
      suicide victims.
AB  - RNA editing is a posttranscriptional process which critically modulates the
      function of several neurotransmitter receptors regulating mood, anxiety,
      learning, and memory. Data from several postmortem studies have shown increased 5
      hydroxytryptamine-2C receptor RNA editing in mood disorders and suicide, and
      therefore the 5-hydroxytryptamine-2C receptor might be expected to have reduced
      signal transduction in these patients. In this study, we have tested the
      hypothesis that the expression levels of the enzymes which catalyze RNA editing,
      adenosine deaminase acting on RNA 1 (ADAR1) and ADAR2, are also abnormal in
      suicide. Gene expression was measured in the dorsolateral prefrontal cortex of
      individuals from the Stanley Consortium Brain series, which includes patients
      with schizophrenia (n=15), major depression (n=15), bipolar disorder (n=15), and
      a comparison group (n=14). Of the psychiatric patients, 20 were suicide victims.
      ADAR1 expression was found to be significantly increased in major depressive
      suicide victims compared with patients who did not commit suicide. Neither ADAR1
      nor ADAR2 expression was altered in any of the other diagnostic groups. These
      data indicate that ADAR1 could play a role in the pathophysiology of suicide in
      patients with major depression.

PMID- 20802354
TI  - Changes in guinea pig cochlea after transient cochlear ischemia.
AB  - Perturbation of cochlear microcirculation, that is, ischemia is a major cause of
      hearing impairment. Earlier studies examined the short-term (<=7 days) effect of
      cochlear ischemia. This study characterized the long-term (4 weeks) functional
      and morphological changes in adult guinea pig cochleae subject to transient
      ischemia by clamping the labyrinthine artery for 0.25-3 h. Notably, cochlear
      ischemia for over 1 h caused an increase of auditory brainstem response
      thresholds and loss of high-frequency hearing, basal-turn hair cells, and spiral
      ganglions. Auditory recovery may be possible after 30-min ischemia. The extent of
      the functional and morphological changes depended on the ischemia period, and the
      changes progressed in extent from the apical to the basal turn in an orderly
      fashion.

PMID- 20802355
TI  - A population-based study of all-terrain vehicle-related head and spinal injuries.
AB  - BACKGROUND: All-terrain vehicles (ATVs) are inherently unstable and their use
      results in numerous injuries annually in the United States. OBJECTIVE: We
      evaluated the magnitude of ATV-related head and spinal column injuries in Utah
      and identified risk factors that might be addressed by preventative measures.
      METHODS: Four statewide trauma and hospital databases were queried to obtain data
      on hospital visits by patients with ATV-related neurological injuries in Utah
      from 2001 to 2005. RESULTS: Seven hundred forty-one patients (median age, 24
      years; range, 2-87 years) with ATV-related head and spinal injuries were
      identified. Five hundred one patients had injuries requiring transport to a
      hospital, of which 261 required intensive care. Five hundred fifty-nine patients
      experienced head trauma and 328 patients sustained spinal trauma. The average
      injury severity score was 12.6 (range, 0-75). Average hospital stay was 4 days
      (range, 0-34 days). Vehicle rollover was the most common mechanism of injury
      (28.6%), followed by loss of control and separation of rider and vehicle (20.1%)
      and collisions with stationary objects (6.1%) or other vehicles (4.1%). Helmet
      use was inconsistently documented, but patients without helmets were more likely
      to have a head injury. Injury frequency increased over time, from 116 in 2001 to
      174 in 2005. CONCLUSION: The number of ATV-related head and spinal injuries is
      increasing in Utah. Serious injuries requiring surgery or intensive care are
      common. Riders under 20 years of age are especially at risk, and helmet use may
      decrease the likelihood of admission to the intensive care unit, head injuries,
      and death.

PMID- 20802356
TI  - Perioperative and long-term outcomes from the management of parasagittal
      meningiomas invading the superior sagittal sinus.
AB  - BACKGROUND: Parasagittal meningiomas invading the superior sagittal sinus (SSS)
      pose formidable obstacles to surgical management. Invasion is often considered a
      contraindication to surgery because of associated morbidity, such as cerebral
      venous thrombosis. OBJECTIVE: We report our most recent experience with the
      resection of parasagittal meningiomas invading the SSS. METHODS: Between 1992 and
      2004, 110 patients with parasagittal meningiomas underwent surgery at the Johns
      Hopkins Medical Institutions. Clinical charts, radiological studies, pathological
      features, and operative notes were retrospectively analyzed; only those patients
      with minimum 24 months follow-up (n = 61) were further studied. RESULTS: Tumor
      distribution by location along the SSS was: 21% anterior, 62% middle, and 17%
      posterior. All patients were managed with initial surgical resection with
      radiosurgery for residual/recurrent disease if indicated (19.6%). Pathological
      examination revealed 80% grade I meningiomas, 13% grade II meningiomas, and 7%
      grade III meningiomas. Simpson grade I/II resection was achieved in 81% of
      patients. Major complications included venous thrombosis/infarction (7%),
      intraoperative air embolism (1.5%), and death (1.5%); long-term outcomes assessed
      included recurrence (11%) and improvement in Karnofsky Performance Score (85%).
      CONCLUSION: On the basis of our study, the incidence of postoperative venous
      sinus thrombosis is 7% in the setting of a recurrence rate of 11% with a mean
      follow-up of 41 months. In comparison with the published literature, the data
      corroborate the rationale for our treatment paradigm; lesions invading the sinus
      can initially be resected to the greatest extent possible without excessive
      manipulation of vascular structures, whereas residual/recurrent disease can be
      observed and managed with radiosurgery.

PMID- 20802357
TI  - Vertebroplasty of the C2 vertebral body and dens using an anterior cervical
      approach: technical case report.
AB  - BACKGROUND AND IMPORTANCE: This article is the first description of an anterior
      approach for a biopsy and vertebroplasty of the C2 body and dens. CLINICAL
      PRESENTATION: A 52-year-old woman presented with a 9-month history of neck pain
      and a destructive lesion of the dens. The patient was treated with pain
      medication as well as steroid injections without relief of her pain. A biopsy and
      vertebroplasty of the C2 body and dens was performed using an anterior cervical
      approach. CONCLUSION: This report describes the first vertebroplasty of C2 using
      an open anterior cervical approach.

PMID- 20802359
TI  - Identification of disappearing brain lesions with intraoperative magnetic
      resonance imaging prevents surgery.
AB  - BACKGROUND: Typically, neurosurgery is performed several weeks after diagnostic
      imaging. In the majority of cases, histopathology confirms the diagnosis of
      neoplasia. In a small number of cases, a different diagnosis is established or
      histopathology is nondiagnostic. The frequency with which these outcomes occur
      has not been established. OBJECTIVE: To determine the frequency and outcome of
      disappearing brain lesions within a group of patients undergoing surgery for
      suspected brain tumor. METHODS: Over the past decade, 982 patients were managed
      in the intraoperative magnetic resonance imaging unit at the University of
      Calgary, Calgary, Alberta, Canada. These patients have been prospectively
      evaluated. RESULTS: In 652 patients, a brain tumor was suspected. In 6 of the 652
      patients, histopathology indicated a nontumor diagnosis. In 5 patients,
      intraoperative images, acquired after induction of anesthesia, showed complete or
      nearly complete resolution of the suspected tumor identified on diagnostic
      magnetic resonance imaging acquired 6 +/- 4 (mean +/- SD) weeks previously.
      Anesthesia was reversed, and the surgical procedure aborted. The lesions have not
      progressed with 6 +/- 2 years of follow-up. CONCLUSION: Intraoperative magnetic
      resonance imaging prevented surgery on 5 patients with disappearing lesions.

PMID- 20802360
TI  - To glue or not to glue? That is the question!!!
AB  - The purpose of Clinical Problem Solving manuscripts is to present management
      challenges in an attempt to give practicing neurosurgeons insight into how field
      leaders address these dilemmas. This illustration is accompanied by a brief
      review of the literature on the topic. We describe the case of a patient who
      presented with recurrent headaches resulting from a nondominant hemisphere
      parietal arteriovenous malformation. Challenges in prognosis, treatment, and
      complication management are discussed.

PMID- 20802361
TI  - Expression of endothelial adhesion molecules after radiosurgery in an animal
      model of arteriovenous malformation.
AB  - BACKGROUND: Endothelial adhesion molecules may be important in the response of
      brain arteriovenous malformations (AVMs) to radiosurgery. In addition to a
      putative role in the occlusive process after radiosurgery, they may serve as
      potential targets for biological strategies to accelerate intravascular
      thrombosis. OBJECTIVE: To determine the temporal expression of E-selectin and
      vascular cell adhesion molecule-1 in an animal model of AVMs. METHODS: Forty-one
      Sprague-Dawley rats underwent surgical creation of a carotid-to-jugular
      anastomosis. Radiosurgery (25 Gy) was delivered to the model "nidus" after 6
      weeks, and the tissue was harvested 1 to 84 days after radiosurgery. Control
      groups received sham irradiation. Immunofluorescence was used to study the
      expression of E-selectin and vascular cell adhesion molecule-1. RESULTS:
      Endothelial E-selectin expression was limited to regions receiving radiosurgery.
      E-selectin expression reached maximal expression at 24 hours after radiosurgery
      and was sustained for another 24 hours before gradually reducing to baseline at
      84 days post-radiosurgery (P < .01). Vascular cell adhesion molecule-1 expression
      remained at the baseline level for the first week; a 50% increase was observed at
      21 days after radiosurgery, which was sustained for another 3 weeks before
      returning to the baseline at 84 days after radiosurgery (P < .05). CONCLUSION:
      Radiosurgery stimulates early expression of E-selectin and delayed up-regulation
      of vascular cell adhesion molecule-1 on the endothelial surface of the AVM model
      nidus. Cell adhesion molecule expression may play an important role in the
      process leading to vascular obliteration after irradiation. These molecular
      alterations may be harnessed to promote thrombosis in the irradiated vasculature
      using a vascular targeting agent.

PMID- 20802362
TI  - Sewing needles in the brain: infanticide attempts or accidental insertion?
AB  - BACKGROUND: Placing of sewing needles in the brain through the anterior
      fontanelle was first described in Germany in 1914. Forty cases have been reported
      in the scientific literature; most of them were identified in Turkey and Iran,
      with only a few cases in the Far East, North and Eastern Europe, and the United
      States. The only case observed in Italy was recorded in 1987. In nonmedical
      literature, this practice was frequently described in Persian novels, and it has
      been thought that this ritual could have been diffused with the Persian Empire
      domination over the centuries. OBJECTIVE: We report on a new Italian case of an
      82-year-old woman admitted for progressive right hemiparesis and gait
      disturbance. METHODS: Brain computed tomography scan showed a left frontoparietal
      chronic subdural haematoma and, surprisingly, three 4-cm-long sewing needles
      inserted through the region of the anterior fontanelle. The patient and her
      friends and family did not remember any event justifying their presence. RESULTS:
      Subdural collection was evacuated by craniotomic approach, and the sewing needles
      were left in place and followed up. CONCLUSION: The rare cases of intracranial
      needling reported in the literature may represent only the tip of the iceberg.
      The phenomenon is usually reported as an incidental finding in asymptomatic
      adults, whereas many babies could not have been diagnosed because they died. The
      therapy remains controversial, although many authors suggest only follow-up for
      asymptomatic patients. In this article, all the pertinent literature is reviewed
      and the most important clinical aspects are discussed, along with a historical
      assessment of the problem.

PMID- 20802363
TI  - Investigation of blood perfusion and metabolic activity of brain tumours in
      adults by using 99mTc-methoxyisobutylisonitrile.
AB  - OBJECTIVES: (i) To examine blood perfusion and metabolic activity of various
      brain tumours using radionuclide cerebral angiography (RCA) and single-photon
      emission tomography (SPET) after a single dose of Tc-methoxyisobutylisonitrile
      (MIBI). (ii) To examine if the inclusion of RCA can improve insight into the
      relative contribution of tumour perfusion to the uptake of MIBI shown by SPET,
      and to improve evaluation of tumour biology. (iii) To determine the value and the
      roles of MIBI in the management of brain tumour patients. METHODS: Fifty adult
      patients (38 male, 12 female) with a total of 56 intracranial space-occupying
      lesions have been included prospectively, 37 of which were newly diagnosed and
      the remaining with signs of recurrence/rest of earlier resected and irradiated
      brain tumours. The control group consisted of nine volunteers with no evidence of
      organic cerebral disease. Scintigraphic examination consisted of a dynamic first
      pass study lasting 60 s (3 s/frame) and two SPET studies (60 projections each, 25
      s/projection), starting 15 min and 2 h after intravenous injection of MIBI.
      Regions of interest of the tumour and normal brain tissue were drawn on RCA and
      both early and delayed SPET slices. The following tumour/brain activity ratios
      have been calculated: (i) tumour perfusion index (P); (ii) early uptake index
      (E); (iii) delayed uptake index (D); and(iv) retention index (R). Analogous
      indices have been calculated from the same examinations performed in controls,
      reflecting maximal physiologic regional variations of perfusion and uptake in
      brain tissue. RESULTS: Mean P of various brain tumours (low-grade gliomas 0.98,
      anaplastic gliomas 1.14, glioblastoma multiforme 1.20, metastases 1.09, lymphomas
      1.08) differ little from each other and do not exceed maximal physiologic
      regional variations of cerebral perfusion (1.33), with the exception of
      meningioma (1.87, F=2.83, P=0.015). The receiver operating characteristics curve
      analysis of P showed that for the cut-off value of 1.45 the sensitivity for
      distinguishing meningioma from other tumours is 75%, specificity 87%, positive
      predictive value 33% and negative predictive value 97%. Mean E of malignant brain
      tumours (8.3, n=31, 23 primary, eight secondary), except anaplastic gliomas (3.5,
      n=5), differed significantly (P=0.02) from those of benign gliomas (3, n=9) but
      not from that of meningioma (11.9, n=4). The cut-off value for distinguishing
      malignant from benign lesions on the basis of E set at 4.8 resulted in
      sensitivity 67%, specificity 75%, accuracy 70%, positive predictive value 80% and
      negative predictive value 60%. D and R showed tendency of wash-out of MIBI from
      meningiomas, but otherwise did not improve the results substantially. CONCLUSION:
      Integrated results of RCA and SPET with Tc-MIBI indicate that blood perfusion,
      blood-tumour barrier permeability and metabolic activity of the tumour are all
      very important for the resultant uptake shown by SPET. If the perfusion index is
      less than 1.45, then meningioma can be ruled out. Early SPET is recommendable for
      distinguishing glioblastoma from low-grade gliomas, as a complement to standard
      magnetic resonance imaging and/or computed tomography.

PMID- 20802364
TI  - Ocular perineuritis secondary to neurosyphilis.
AB  - BACKGROUND: Syphilis is a condition caused by the spirochete Treponema pallidum
      (T. pallidum). Because of its ubiquitous nature, it has been coined as "the great
      masquerader." Syphilis can present with a wide array of clinical symptoms and
      manifestations, making it difficult to diagnose. The spectrum of visual system
      manifestations is broad and involves the anterior and posterior segments. We
      report a rare case of ocular perineuritis in an HIV-positive patient with
      neurosyphilis. CASE REPORT: A 33-year-old HIV-positive white male presented with
      blurred vision and floaters of 2 weeks duration. He reported coinciding
      neurological symptoms including headaches, nausea, and extreme weight loss. He
      also manifested an erythematous rash on his scalp. Fundoscopy revealed bilateral
      disc edema. CONCLUSIONS: Syphilitic ocular perineuritis is a condition that
      manifests with swollen optic discs in the absence of raised intracranial pressure
      or visual disturbance. This condition is due to inflammation of the optic nerve
      sheath and is often mistaken for papilledema or papillitis. Optic perineuritis is
      an infrequently reported complication of syphilitic disease. Early diagnosis of
      neurosyphilis and its complications is critical, because it is easily treated
      with penicillin when initiated early on.

PMID- 20802365
TI  - Factor analysis of the clinical characteristics of primary Sjogren syndrome.
AB  - PURPOSE: The purpose of this study was to use factor analysis to analyze 90
      clinical characteristics of a cohort of 231 patients with primary Sjogren
      syndrome (pSS). METHODS: The records of all patients seen at the University
      Health Network Sjogren Syndrome Clinic from October 1992 to July 2006 were
      reviewed and documented. Those diagnosed as pSS by the American European
      Consensus Criteria of 2002 were included. The 90 clinical variables, including
      health history, blood analysis, symptoms of dry eye and dry mouth, salivary flow
      and biopsy, tear flow and staining, were analyzed by factor analysis. RESULTS:
      Two hundred thirty-one patients with pSS charts were reviewed, and 90 variables
      were recorded. Factor analysis resulted in three factors: factor 1: ocular
      surface staining, factor 2: antimicrosomal antibodies and antithyroid antibodies,
      and factor 3: serum anti-Ro and anti-La. CONCLUSIONS: Ocular surface staining
      accounted for the greatest variance in this population of patients with pSS.

PMID- 20802366
TI  - Measuring near-induced transient myopia in college students with visual
      discomfort.
AB  - PURPOSE: Visual discomfort is a common problem, and our previous research
      indicated that 17% of college students experience moderate to high levels of
      discomfort when reading or studying. There have been several visual factors
      associated with visual discomfort, and in this study, we focused on measuring the
      near-induced transient myopia response in a group of college students with
      significant visual discomfort. METHODS: Visual discomfort was evaluated with a
      survey developed by Conlon et al. (Conlon et al., Visual Cogn 1999;6:637-663).
      Twelve college students with high visual discomfort (scoring 1 SD higher than the
      mean value) and 12 college students with low visual discomfort (scoring within
      0.5 SD of the mean value) participated in the study. All students had 20/25 or
      better visual acuity, no strabismus, and no significant uncorrected refractive
      error. All refractive error and accommodative measurements were made with the WAM
      5500 autorefractor. A pretask distance refraction at 6 m was taken for 60 s, and
      then the students read a story for 10 min at 20 cm. After reading the passage,
      the posttask distance refraction was measured for 2 min at 6 m. Values for the
      pre- and posttask measures were averaged in 10-s blocks of time. RESULTS: A mixed
      analysis of variance comparing discomfort group by pre- and postnear work
      distance refraction showed a significant interaction (p = 0.05). Comparing the
      means of the pre- and posttask distance refraction indicated that the high
      discomfort group showed no change in refractive error, but the low discomfort
      group showed a myopic shift of 0.13 diopter. CONCLUSIONS: A near-induced
      transient myopia response is not associated with high visual discomfort
      experienced by college students when reading or doing near work.

PMID- 20802367
TI  - Prevention and treatment of meningitis and acute otitis media in children with
      cochlear implants.
AB  - OBJECTIVE: To provide recommendations for 1) prevention of acute otitis media and
      meningitis via immunization and 2) antimicrobial therapy of acute otitis media
      and meningitis in children with cochlear implants. DATA SOURCES: Literature
      review and policy statement from the American Academy of Pediatrics. CONCLUSION:
      1) Children who are candidates for cochlear implants or have received cochlear
      implants should receive all-age appropriate vaccinations, including indicated
      doses of 13-valent pneumococcal conjugate vaccine, Haemophilus influenzae type b
      conjugate vaccine, and influenza vaccine. A supplemental dose of 13-valent
      pneumococcal conjugate vaccine is indicated for children who have received
      indicated doses of 7-valent pneumococcal vaccine, but have not received 13-valent
      pneumococcal conjugate vaccine. In addition, children 24 months and older should
      receive a single dose of 23-valent pneumococcal polysaccharide vaccine. 2) Acute
      otitis media in children with cochlear implants should be treated with an
      antimicrobial. During the first 2 months after implant, initial treatment of
      acute otitis media with a parenteral antimicrobial, e.g., cetriaxone, is
      indicated. High-dose amoxicillin or amoxicillin-clavulanate is an appropriate
      antimicrobial choice for empiric treatment of acute otitis media occurring 2 or
      more months after implant. In cases of meningitis occurring during the first 2
      months after implantation, broad spectrum empiric antimicrobial therapy, e.g.,
      meropenem and vancomycin, should be initiated pending the results of CSF culture.
      Empiric antimicrobial therapy with ceftriaxone and vancomycin is appropriate for
      cases of meningitis occurring 2 or more months after implant.

PMID- 20802368
TI  - A public health perspective on cochlear implants and meningitis in children.

PMID- 20802369
TI  - Bilateral cochlear implants in infants: a new approach--Nucleus Hybrid S12
      project.
AB  - OBJECTIVE: The purpose of this feasibility study was to evaluate whether the use
      of a shorter-length cochlear implant (10 mm) on one ear and a standard electrode
      (24 mm) on the contralateral ear is a viable bilateral option for children with
      profound bilateral sensorineural hearing loss. A secondary purpose of this study
      was to determine whether the ear with the shorter-length electrode performs
      similarly to the standard-length electrode. Our goal was to provide an option of
      electrical stimulation that theoretically might preserve the structures of the
      scala media and organ of Corti. STUDY DESIGN: The study is being conducted as a
      repeated-measure, single-subject experiment. SETTING: University of Iowa
      Department of Otolaryngology. PATIENTS: Eight pediatric patients with profound
      bilateral sensorineural hearing loss between the ages of 12 and 24 months.
      INTERVENTIONS: Nucleus Hybrid S12 10-mm electrode and a Nucleus Freedom implant
      in the contralateral ear. MAIN OUTCOME MEASURES: The Infant-Toddler Meaningful
      Auditory Integration Scale (IT-MAIS) parent questionnaire, Early Speech
      Perception, Glendonald Auditory Screening Procedure word test, and Children's
      Vowel tests will be used to evaluate speech perception and the Minnesota Child
      Development Inventory and Preschool Language Scales 3 test will be used to
      evaluate language growth. RESULTS: Preliminary results for 8 children have been
      collected before and after the operation using the IT-MAIS. All 3 children showed
      incremental improvements in their IT-MAIS scores overtime. Early Speech
      Perception, Glendonald Auditory Screening Procedure word test, and Children's
      Vowel word perception results indicated no difference between the individual ears
      for the 2 children tested. Performance compared with age-matched children
      implanted with standard bilateral cochlear implants showed similar results to the
      children implanted with Nucleus Hybrid S12 10-mm electrode and a Nucleus Freedom
      implant in contralateral ears. CONCLUSION: The use of a shorter-length cochlear
      implant on one ear and a standard-length electrode on the contralateral ear might
      provide a viable option for bilateral cochlear implantation in children with
      bilateral profound sensorineural hearing loss. Further study of this patient
      population will be continued.

PMID- 20802370
TI  - Impact of hair cell preservation in cochlear implantation: combined electric and
      acoustic hearing.
AB  - OBJECTIVE: This article reviews some of the potential benefits of preserving low
      frequency residual hearing using a short-electrode cochlear implant. Both the
      status of the inner ear and acoustic characteristics of speech cues are important
      factors. How does the magnitude of the potential benefits depend on the candidacy
      criteria for implantation with a hearing-preservation electrode? BACKGROUND:
      Previous research has demonstrated that preserving residual hearing in cochlear
      implantation can provide significant advantages for the understanding of speech
      in background noise as well as for the aesthetic qualities of music and other
      sounds. Developing optimal candidacy guidelines for these devices is a current
      goal. METHODS: In a large group of patients with Hybrid (acoustic + electric)
      cochlear implant, performance in the recognition of speech in background of other
      talkers is measured and compared with patients with traditional long-electrode
      implant. In addition, a number of patient characteristics are compared to success
      with the short-electrode implant. RESULTS: Age and duration of hearing loss are
      found to be predictive factors for the success of the short-electrode approach.
      CONCLUSION: Optimal criterion for candidacy for the use of the short-electrode
      versus a traditional long electrode can improve the outlook for patients with
      severe-to-profound high-frequency hearing loss.

PMID- 20802371
TI  - A longitudinal study on auditory perception and speech intelligibility in deaf
      children implanted younger than 18 months in comparison to those implanted at
      later ages.
AB  - OBJECTIVE: The objective of this study was to measure longitudinally the progress
      in the auditory performance and speech intelligibility of young deaf children
      implanted under the age of 18 months in comparison to those implanted after 18
      months and to create normative data on these children implanted under 18 months.
      STUDY DESIGN: : This is a retrospective longitudinal study based on data
      available at our centre 'KIDS-Hasselt-Belgium'. PATIENTS: 52 deaf children who
      received a cochlear implant under the age of 18 months. METHODS: LiP (Listening
      Progress profile) and CAP (Categories of Auditory Performance) were administered
      to measure auditory perception and SIR (Speech Intelligibility Rating) was used
      to measure speech intelligibility. Over a 4 year period, six assessments were
      made to monitor the auditory and speech development of the children: a pre-test
      before implantation and five post-tests at 6, 12, 24, 36 and 48 months after
      implantation. RESULTS: Deaf children receiving cochlear implants before the age
      of 18 months show more rapid progress in auditory performance and speech
      intelligibility in comparison to children implanted at an older age. Their
      auditory performance and speech intelligibility also reach a higher level 4 years
      after implantation compared with children implanted later in life. DISCUSSION AND
      CONCLUSION: This study shows encouraging results in the cochlear implantation of
      children under the age of 18 months. As demonstrated, using the LiP, CAP and SIR
      measures, children who receive a cochlear implant before the age of 18 months
      show, that at 3 to 4 years after implantation, significantly greater improvement
      is made in auditory perception and speech intelligibility than their later
      implanted peers, although there is a considerable variety in the outcomes.

PMID- 20802372
TI  - Impact of partial mastoid obliteration on caloric vestibular function in canal
      wall down mastoidectomy.
AB  - OBJECTIVE: To evaluate the influence of our technique of partial mastoid
      obliteration with autologous bone pate covered by cartilage plates on vestibular
      stimulation. METHODS: Twenty-six patients who were treated for recurrent chronic
      otitis media by revision canal wall down tympanomastoidectomy and subsequent
      partial obliteration were invited for follow-up; 18 patients agreed to a complete
      follow-up including vestibular testing. Patients received questionnaires for
      evaluating preoperative and postoperative symptoms associated with vertigo.
      Examination comprised otomicroscopy, pure-tone audiometry, and caloric testing.
      RESULTS: Mean follow-up was 6 years. Before surgery, 54% of the patients reported
      vertigo on caloric stimuli such as wind, water, or suction cleaning of the
      tympanomastoid cavity. In all patients, these symptoms were suspended after
      partial mastoid obliteration. The postoperative obliterated cavity volume
      averaged 3.1 ml. All cavities after surgery appeared completely epithelialized
      and dry. The postoperative caloric vestibular tests revealed an average nystagmus
      count of 46 beats per minute compared with 72 beats before surgery. Thus, the
      partial mastoid cavity obliteration led to a mean nystagmus reduction of 36% in
      our study group. CONCLUSION: Our technique of partially obliterating
      tympanomastoid cavities with autologous bone pate being covered by cartilage
      plates results in small cavities with complete epithelialization of all surfaces.
      Furthermore, obliteration of mastoid cavities confers protection to the
      labyrinthine organ, thereby reducing postoperative vertigo on caloric
      stimulation.

PMID- 20802373
TI  - Detection of bacterial biofilm on cochlear implants removed because of device
      failure, without evidence of infection.
AB  - OBJECTIVE: To investigate the formation of bacterial biofilms on the surface of
      the electrode array of cochlear implants (CI) explanted because of device
      failure, without evidence of infection, by use of scanning electron microscopy
      (SEM) and confocal laser scanning microscopy (CLSM). STUDY DESIGN: Prospective
      study. SETTING: Patients from 2 tertiary-care referral centers. PATIENTS AND
      METHODS: CIs were explanted from 9 patients because of device failure. Specimens
      were immediately snap-frozen in cold isopenthane, stored at -80 degrees C and
      examined with SEM and CLSM by 3 investigators. MAIN OUTCOME MEASURE: Presence of
      bacterial biofilm ascertained by SEM and CSLM. RESULTS: One specimen showed the
      formation of a bacterial biofilm on the middle ear part of the electrode array.
      No biofilm formation was found in the inner-ear part of electrode arrays. In the
      middle-ear part of the electrode array, a cylindrical cover of human muscular
      tissue was seen plugging the cochleostomy. CONCLUSION: This is the first study
      demonstrating that bacterial biofilms may exist on the surface of the electrode
      array of CIs explanted because of device failure but not infection. We found 1
      case of biofilm formation in 9 explanted CIs. Further studies with larger series
      of CIs are required to investigate biofilm formation on the surface of CI
      electrode arrays to address both the pathophysiology of bacterial biofilms and
      prevention of device-related infections in CI patients.

PMID- 20802374
TI  - Pandemic influenza a (2009 H1N1) in human immunodeficiency virus-infected catalan
      children.
AB  - No data are available on 2009 H1N1 influenza in human immunodeficiency virus
      (HIV)-infected children, a highly susceptible and vulnerable population. We
      report 13 cases of pandemic influenza among a cohort of HIV-infected pediatric
      patients. Clinical features of H1N1 influenza were similar to those described in
      the general population. Most patients received antivirals on an outpatient basis.
      An uneventful evolution was observed in all patients, only 2 of whom required
      hospitalization. Influenza had no effect on the evolution of HIV infection.

PMID- 20802375
TI  - External validation of a risk score to predict intravenous immunoglobulin
      resistance in patients with kawasaki disease.
AB  - BACKGROUND: we previously developed a new risk score to predict intravenous
      immunoglobulin (IVIG) resistance in Kawasaki disease. However, the IVIG dosage
      used in that study (1 g/kg/d for 2 consecutive days) differs from the single
      infusion of 2 g/kg recommended in the United States and elsewhere. Our aim was to
      assess the validity and applicability of our risk score in patients treated with
      a single infusion. METHODS: we used a database of 1626 patients with Kawasaki
      disease given initial IVIG treatment at a dose of 1 g/kg/d for 2 consecutive days
      (n = 990; IVIG- 1 g/kg * 2) or 2 g/kg/d for 1 day (n = 636; IVIG- 2 g/kg * 1)
      across 17 hospitals in Japan. Patients received the total IVIG dose within 36
      hours in IVIG- 1 g/kg * 2 and 24 hours in IVIG- 2 g/kg * 1. We stratified the
      patients according to a risk scoring system developed to predict IVIG
      unresponsiveness, based on scores of >= 5 points. We compared the accuracy of
      prediction between the 2 groups using receiver operating characteristic analysis.
      RESULTS: baseline characteristics and clinical outcomes were similar between both
      groups. The areas under the receiver operating characteristic curve in IVIG- 2
      g/kg * 1 were similar to those of IVIG- 1 g/kg * 2. Using a cut-off risk score of
      >= 5 points, we could identify IVIG resistance in terms of coronary artery
      abnormalities within 1 month and coronary artery abnormalities at 1 month with
      equivalent sensitivity and specificity in both groups. CONCLUSION: our risk score
      can be used to predict IVIG unresponsiveness to a regimen based on a single
      infusion of 2 g/kg IVIG.

PMID- 20802376
TI  - Effect of cortisol on C-type natriuretic peptide in ovine pregnancy: differential
      responses in fetal and placental tissues.
AB  - We have used aminoterminal pro C-type natriuretic peptide (NTproCNP)--a stable
      marker of CNP secretion--to study the effect of cortisol on CNP secretion and
      fetal growth. In ovine pregnancy, maternal plasma NTproCNP (largely sourced from
      the placenta) increases at the end of the first trimester and then decreases
      abruptly preterm during the phase of fetal surge in cortisol secretion.
      Postulating that increases in cortisol, as occurs in the fetal or maternal
      circulation in late pregnancy, will reduce CNP secretion, we studied the fetal
      and maternal responses in NTproCNP to sustained low-dose infusions of cortisol
      (1.2 mg/d/kg for 11 d) delivered to the fetus from d 117 gestation. Fetal plasma
      NTproCNP was progressively reduced during fetal cortisol infusions, whereas fetal
      girth growth was unchanged. In contrast, maternal NTproCNP was unaffected by
      cortisol. We conclude that fetal but not placental tissue production of CNP is
      reduced by small increments in fetal cortisol. Failure to reduce maternal
      NTproCNP may relate to the continuing presence of the placental barrier to
      cortisol at this stage of pregnancy.

PMID- 20802377
TI  - Glutathione S-transferase M1 (GSTM1) genotype but not GSTT1 or MC1R genotype
      influences erythemal sensitivity to narrow band (TL-01) UVB phototherapy.
AB  - OBJECTIVES: Although a majority of psoriasis patients respond to treatment with
      narrow band ultraviolet B radiation (TL-01) phototherapy, it is currently not
      possible to predict erythemal sensitivity, or to identify treatment responders. A
      variety of antioxidant enzymes, including the polymorphic glutathione S
      transferase GSTM1 and GSTT1 genes, protect the cell from UVR-induced oxidative
      challenge. GSTM1 and GSTT1 are deleted in approximately 50 and 20% of the
      Caucasian population, respectively, and GST null genotype has been associated
      with increased sunburn sensitivity and reduced minimal erythemal dose (MED) after
      broadband UVR exposure in healthy volunteers and with susceptibility to skin
      cancer. Another polymorphic determinant of UVR sensitivity is the melanocortin 1
      receptor (MC1R), which protects cells from UVR-induced apoptosis and photodamage.
      Our aim was therefore to investigate whether GST or MC1R genotype influenced
      erythemal sensitivity to narrow band (TL-01) ultraviolet B radiation phototherapy
      in patients with psoriasis. METHODS: We used TaqMan quantitative gene copy and
      allelic discrimination assays to determine GST and MC1R genotypes, and looked for
      possible associations between genotype and threshold erythemal sensitivity (MED)
      and treatment outcomes in patients with psoriasis (n=256). RESULTS: We showed
      that GSTM1 genotype, but not GSTT1 or MC1R genotype influences erythemal
      sensitivity to TL-01 phototherapy, with a significantly lower MED observed in
      GSTM1 null individuals [chi(2 d.f.)=8.862, P=0.012]. None of the genotypes
      studied were associated with TL-01 treatment outcomes or relapse rates.
      CONCLUSION: GSTM1 genotype may have clinical utilityin the prediction of
      photosensitivity and/or in identifying patients at increased risk of treatment
      related side effects.

PMID- 20802378
TI  - A multiplex MALDI-TOF MS approach facilitates genotyping of DNA from formalin
      fixed paraffin-embedded tumour specimens.
AB  - OBJECTIVE: The impact of single-nucleotide polymorphisms (SNPs) on tumour
      susceptibility and pathogenesis has gained enormous attention. Matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based
      genotyping facilitates the analysis of short DNA amplicons and is, therefore, a
      promising tool for the investigation of formalin-fixed paraffin-embedded (FFPE)
      tissue samples, particularly in targeted genotyping analysis. METHODS: To examine
      the applicability of genotyping FFPE DNA with MALDI-TOF MS in multiplex
      reactions, we investigated five DNA samples extracted from FFPE tumour specimens
      from follicular lymphoma patients using different extraction methods (phenol
      chloroform, commercial kit). Thirty-one SNPs from 25 genes, integrated in
      different-sized multiplex assays (7-plex, 10-plex, 14-plex, 24-plex), were
      analyzed. To investigate the reliability of genotyping tumour-derived DNA
      extracted from FFPE tissue, we examined 64 FFPE tumour specimens in comparison
      with matched germline DNA samples. RESULTS: Call rates of 99.6 (274/275) and
      93.5% (257/275) were observed for the DNA extracted with the phenol-chloroform
      approach or the commercial extraction kit, respectively. Increasing the number of
      SNPs per assay resulted in reduced genotyping call rates and genotyping quality,
      especially in the DNA samples isolated with the commercial extraction kit. When
      comparing the genotypes of DNA derived from germline and tumour (FFPE) specimens,
      a perfect concordance rate of 100% was detected. CONCLUSION: Our data delineate
      that MALDI-TOF-based genotyping of FFPE DNA is reliable and reproducible even in
      multiplex reactions, enabling the retrospective investigation of FFPE study
      cohorts in future experiments.

PMID- 20802379
TI  - Long fish bone embedded intramurally in the cervical esophagus.

PMID- 20802380
TI  - Hemorrhagic tamponade due to cardiac angiosarcoma.
AB  - Prognosis of angiosarcoma, the most common primary malignant cardiac tumor, is
      very poor. An early detection and treatment may extend survival beyond one year.
      Newer imaging modalities, including magnetic resonance imaging (MRI), play an
      important role in the evaluation of cardiac masses. The case of a man admitted to
      the emergency room for a cardiac tamponade is reported. Thoracic computed
      tomography and MRI diagnosed a pericardial tumor, for which surgical biopsy
      revealed an angiosarcoma. Chemotherapy was started, and the patient survived for
      28 months. Etiologies of hemorrhagic tamponades are discussed, as well as
      treatment of cardiac angiosarcoma.

PMID- 20802381
TI  - Hyperprothrombinemia as a result of a possible warfarin and intravaginal
      miconazole interaction.
AB  - Warfarin, a commonly prescribed anticoagulant, has many potential drug
      interactions. We describe a case of intravaginal miconazole potentiating the
      effects of warfarin in a patient previously stable on a consistent dose of 8.5 mg
      warfarin daily. Following a course of intravaginal miconazole and a dosage
      increase to 9 mg daily, her international normalized ratio (INR) increased from
      2.0 to 5. After the course of miconazole was complete, the patient was stable
      with a therapeutic INR (mean INR 2.9) on 9 mg warfarin daily. Clinicians should
      consider the possibility of systemic absorption of intravaginal miconazole, and a
      resultant increase in warfarin's anticoagulant effect.

PMID- 20802382
TI  - Preoperative and perioperative factors effect on adolescent idiopathic scoliosis
      surgical outcomes.
AB  - STUDY DESIGN: Prospective multicenter database. OBJECTIVE: To identify factors
      associated with outcomes from adolescent idiopathic scoliosis (AIS) surgery
      outcomes and especially poor results. SUMMARY OF BACKGROUND DATA: Because AIS is
      rarely symptomatic during adolescence, excellent surgical results are expected.
      However, some patients have poor outcomes. This study seeks to identify factors
      correlating with results and especially those making poor outcomes more likely.
      METHODS: Demographic, surgical, and radiographic parameters were compared to 2
      year postoperative Scoliosis Research Society (SRS) scores in 477 AIS surgical
      patients using stepwise linear regression to identify factors predictive of 2
      year domain and total scores. Poor postoperative score patients (>2 SD below
      mean) were compared using t tests to those with better results. RESULTS: The SRS
      instrument exhibited a strong ceiling effect. Two-year scores showed more
      improvement with greater curve correction (self-image, pain, and total), and were
      worse with larger body mass index (pain, mental, total), larger preoperative
      trunk shift (mental and total), larger preoperative Cobb (self-image), and
      preoperative symptoms (function). Poor results were more common in those with
      Lenke 3 curve pattern (pain), less preoperative coronal imbalance, trunk shift
      and rib prominence (function), preoperative bracing (self-image), and anterior
      procedures (mental). Poor results also had slightly less average curve correction
      (50% vs. 60%) and larger curve residuals (31 degrees  vs. 23 degrees ).
      Complications, postoperative curve magnitude, and instrumentation type did not
      significantly contribute to postoperative scores, and no identifiable factors
      contributed to satisfaction. CONCLUSION: Curve correction improves patient's self
      image whereas pain and poor function before surgery carry over after surgery.
      Patients with less spinal appearance issues (higher body mass index, Lenke 3
      curves) are less happy with their results. Except in surgical patient selection,
      many of these factors are beyond physician control.

PMID- 20802383
TI  - Changes in radiographic and clinical outcomes with primary treatment adult spinal
      deformity surgeries from two years to three- to five-years follow-up.
AB  - STUDY DESIGN: Retrospective analysis of data entered prospectively into a
      multicenter database-clinical and radiographic outcomes assessment. OBJECTIVE:
      Our hypothesis is that between the 2-year and the 3- to 5-year points surgically
      treated adult spinal deformity patients will show significant reduction in
      outcomes by Scoliosis Research Society (SRS), Oswestry Disability Index (ODI),
      and numerical rating scale back and leg pain scores and will show increasing
      thoracic kyphosis, loss of lumbar lordosis, and loss of coronal and sagittal
      balance. SUMMARY OF BACKGROUND DATA: Most analyses of primary presentation adult
      spinal deformity surgery assess 2-year follow-up. However, it is established that
      in some patients unfavorable events occur between the 2-year and 5-year points.
      METHODS: The cohort of 113 patients entered into a multicenter database with
      complete preoperative, 2-year, and 3- to 5-year data. All patients who had adult
      spinal deformity and surgical treatment represented their first reconstruction.
      Diagnoses were scoliosis (82.5%), kyphosis (10%), and scoliosis and kyphosis
      combined (7.5%). Outcome measures and basic radiographic parameters (curve size,
      thoracic and lumbar sagittal plane, coronal and sagittal balance) were assessed
      at those 3 time intervals. Complications (pseudarthrosis/implant failure,
      infection, and junctional deformities) were assessed at the 2-year and the 3- to
      5-year (mean, 3.76 years) points. RESULTS.: The mean major curve Cobb angle
      (preoperative, 57 degrees ; 2-year, 29 degrees ; 3-5 year, 26 degrees ); thoracic
      kyphosis T5 to T12 (30 degrees , 31 degrees , 32 degrees ) and lumbar lordosis
      T12 to sacrum (48 degrees , 49 degrees , 51 degrees ) did not change from the 2
      year to ultimate follow-up. Likewise, coronal and sagittal balance parameters
      were the same at 2-year and ultimate follow-up. SRS total scores and modified ODI
      were similar at the 2 year and final follow-up (SRS: 3.89-3.88; ODI: 19-18).
      Preoperative SRS total score was 3.17. Six patients demonstrated complications at
      the 2-year point and additional 9 patients demonstrated complications at the 3-
      to 5-year point. Those 9 patients with complications at ultimate follow-up
      demonstrated significant deterioration in their ODI and SRS scores when compared
      with the patients who did not have complications at ultimate follow-up.
      CONCLUSION: Contrary to our hypothesis, we could not establish deterioration in
      mean radiographic or clinical outcomes between the 2-year and 3- to 5-year follow
      up points when analyzing the group as a whole. However, for the 9 patients who
      experienced complications between 3- and 5-year follow-up, their outcomes were
      significantly worse than for the other 104 patients.One should not anticipate an
      overall radiographic and clinical deterioration of the outcomes of surgically
      treated primary presentation adult spinal deformity patients in this studied time
      interval. However, close to 10% of patients will experience a new complication at
      the 3- to 5-year point, most commonly implant failure/nonunion and/or junctional
      kyphosis, which will negatively effect the patient-reported outcome.

PMID- 20802384
TI  - Hydromyelia associated with spinal lipoma of the conus: case report.
AB  - STUDY DESIGN: A case report and literature review of the treatment of
      "noncommunicating" syringomyelia. OBJECTIVE.: The aim of this report is to
      document the timing and the treatment of hydromyelia holocord after surgical
      treatment for both tethering and retethering of spinal lipoma. SUMMARY OF
      BACKGROUND DATA: Syringomyelia associated with spinal lipoma presents a different
      pathogenesis and treatment in comparison to the "communicating" hydromyelia in
      the myelomeningocele. After the primary retethering operation performed in
      symptomatic patients, recurrent retethering can occur with an increase of the
      syringomyelia signs and symptoms. METHODS: Syringomyelia treated with a thin
      silastic tube passed from the syrinx to the subarachnoidal space for drainage and
      decompression. Prior operations were: (1) initial untethering at birth, (2)
      second untethering at 5 years of age, (3) posterior fossa and cervical
      decompression. RESULTS: Magnetic resonance imaging 6 months post shunt operation
      demonstrated decompression of the hydromyelia holocord and syringobulbia with
      improvement of motor function of the legs and improvement in sensory symptoms.
      CONCLUSION: Usefulness of syrinx-subarachnoidal shunt is demonstrated in this
      case report after unsuccessful decompression and detethering. When the
      enlargement of the ependymal channel is greater than 50% of the spinal cord's
      diameter, neurologic, and urological symptoms are evident and the patient
      benefitted from cord untethering and syrinx drainage. (1) The terminal
      "noncommunicating" syringomyelia in lumbar sacral lipoma has been reported to be
      associated with retethering in spinal lipoma in the 25% of the cases. (2) The
      rise of distal syringomyelia isn't only linked to the kind of the spinal lipoma,
      but also to the difficulty to obtain the untethering and a smooth cerebrospinal
      fluid flow between the subarachnoidal space and the ependymal canal. (3) In
      patients with hydromyelia holocord greater than the 50% of the spinal cord's
      diameter a myelotomy and insert an ependymal channel/syrinx to the subarachnoidal
      space shunt can resolve of the syrinx. In this case, the enlargement of the
      ependymal channel in "noncommunicating" syringomyelia associated with lumbosacral
      lipoma is greater than 50% of the spinal cord's diameter; neurologic and
      urological symptoms occurred and the patient benefited from cord untethering and
      concurrent syrinx drainage.

PMID- 20802385
TI  - Descending aortic injury by a thoracic pedicle screw during posterior
      reconstructive surgery: a case report.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe an iatrogenic aortic injury by
      pedicle screw instrumentation during posterior reconstructive surgery of spinal
      deformity. SUMMARY OF BACKGROUND DATA: Iatrogenic major vascular injuries during
      anterior instrumentation procedures have been reported by several authors, but
      there have been few reports regarding iatrogenic major vascular injuries during
      posterior instrumentation procedures. METHODS: A 57-year-old woman with
      thoracolumbar kyphosis due to osteoporotic T12 vertebral fracture underwent
      posterior correction and fusion (T10-L2), using segmental pedicle screw construct
      concomitant with T12 pedicle subtraction osteotomy. Postoperative routine plain
      radiographs and computed tomography myelography demonstrated a misplaced left T10
      pedicle screw, which was in contact with the posteromedial aspect of the thoracic
      aorta, and suspected penetration of the aortic wall. The patient underwent
      removal of the pedicle screw, and repair of the penetrated aortic wall through a
      simultaneous anterior-posterior approach. RESULT: The patient tolerated the
      procedure well without neurologic sequelae, and was discharged several days after
      removal of a left tube thoracostomy. Plain radiographs demonstrated solid fusion
      at the osteotomy site and no loosening of hardware. Preoperative neurologic
      symptoms improved completely at 18-months follow-up. CONCLUSION: Use of pedicle
      screw instrumentation has the potential to cause major vascular injury during
      posterior spinal surgery, and measures to prevent this complication must be
      taken. Timely diagnosis and treatment are essential to prevent both early and
      delayed complications and death.

PMID- 20802386
TI  - Efficacy of prophylactic placement of inferior vena cava filter in patients
      undergoing spinal surgery.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: To evaluate the safety and
      efficacy of prophylactic inferior vena cava filter (IVCF) to prevent pulmonary
      embolism (PE) in high risk patients undergoing major complex spinal surgery.
      SUMMARY OF BACKGROUND DATA: PE has been reported to be the major cause of death
      after spinal reconstructive surgery. Mechanical prophylaxis alone is often not
      sufficient whereas anticoagulation therapy carries a significant risk of bleeding
      complications. Prophylactic IVCF placement is advocated in high-risk patients.
      METHODS: A total of 129 high-risk patients undergoing complex spine surgery,
      having prophylactic IVCF were compared to a matched cohort of age, diagnosis, and
      risk factors of 193 patients for whom only mechanical prophylaxis was used.
      Patients were observed for potential complications related to the IVCF and also
      for clinical signs and symptoms of PE. RESULTS: Eight cases (4.2%) of symptomatic
      PE were detected in the matched cohort control group (5 cases having combined
      anterior + posterior surgery and 3 patients having only posterior surgery). One
      of them died due to massive PE (0.5%). Symptomatic PE was detected in only 2
      patients (1.5%), having combined anterior + posterior surgery due to lumbar
      spinal stenosis in IVCF group who responded well to medical treatment (P < 0.05).
      No complications were associated with filter insertion. CONCLUSION: Prophylactic
      IVCF is effective and safe in prevention of pulmonary embolism in patients with
      risk factors for PE.

PMID- 20802387
TI  - Functional outcomes and complications after primary spinal surgery for scoliosis
      in adults aged forty years or older: a prospective study with minimum two-year
      follow-up.
AB  - STUDY DESIGN: A prospective study. OBJECTIVE: Our purpose was to evaluate
      prospectively the complications, clinical outcomes, and self-reported quality of
      life in a relatively homogenous group of adults aged >= 40 years undergoing
      primary surgical treatment for scoliosis. SUMMARY OF BACKGROUND DATA: Relatively
      few reports have examined surgical outcomes in adult patients with scoliosis,
      especially adults aged >= 40 years, whose outcomes may differ because of more
      rigid curves and more frequent and severe comorbidities. Although most studies
      have shown patient benefits despite high complication rates after such surgery,
      most were retrospective and conducted before the introduction of third-generation
      instrumentation techniques. METHODS: We prospectively studied a consecutive
      series of 35 patients of age >= 40 years (average age, 56.3 years) undergoing
      primary surgery for scoliosis by one surgeon. Most of our patients (86%) had at
      least one comorbidity. We collected complete radiographic measurements and
      Oswestry Disability Index, Short Form 36, and Scoliosis Research Society 22
      questionnaires before surgery and at each follow-up, and recorded the number and
      type of complications. Outcomes were assessed in the context of complications,
      degree of correction, and procedure characteristics to detect significant (P <
      0.05) correlations. RESULTS: The overall complications rate was 49%; 26% of the
      patients had a major complication and 31% had a minor one. There were no deaths.
      Coronal curve correction was 30.8 degrees  (61%) on average. There were
      statistically significant postoperative improvements in Oswestry Disability
      Index, Short Form 36, and Scoliosis Research Society 22 scores. Patients whose
      fusions ended at L4 or L5 showed greater improvements in some of the Short Form
      36 component scores than patients whose fusions involved the sacrum (P = 0.041).
      There were no significant differences in outcomes related to presence of
      complications or operative staging. CONCLUSION: Adults >= 40 years with
      symptomatic scoliosis benefit from surgical treatment, despite the high
      complication rate.

PMID- 20802388
TI  - Validity and reliability of intraoperative monitoring in pediatric spinal
      deformity surgery: a 23-year experience of 3436 surgical cases.
AB  - STUDY DESIGN: This was a 23-year retrospective study of 3436 consecutive
      pediatric orthopedic spinal surgery patients between 1995 and 2008. OBJECTIVE: To
      demonstrate the effectiveness of multimodality electrophysiologic monitoring in
      reducing the incidence of iatrogenic neurologic deficit in a pediatric spinal
      surgery population. SUMMARY OF BACKGROUND DATA: The elective nature of many
      pediatric spinal surgery procedures continues to drive the need for minimizing
      risk to each individual patient. Electrophysiologic monitoring has been proposed
      as an effective means of decreasing permanent neurologic injury in this
      population. METHODS: A total of 3436 consecutive monitored pediatric spinal
      procedures at a single institution between January 1985 and September 2008 were
      reviewed. Monitoring included somatosensory-evoked potentials, descending
      neurogenic-evoked potentials, transcranial electric motor-evoked potentials, and
      various nerve root monitoring techniques. Patients were divided into 10
      diagnostic categories. True-positive and false-negative monitoring outcomes were
      analyzed for each category. Neurologic deficits were classified as transient or
      permanent. RESULTS: Seven of 10 diagnostic groups demonstrated true positive
      findings resulting in surgical intervention. Seventy-four (2.2%) potential
      neurologic deficits were identified in 3436 pediatric surgical cases. Seven
      patients (0.2%) had false-negative monitoring outcomes. These patients awoke with
      neurologic deficits undetected by neuromonitoring. Intervention reduced permanent
      neurologic deficits to 6 (0.17%) patients. Monitoring data were able to detect
      permanent neurologic status in 99.6% of this population. The ratio of
      intraoperative events to total monitored cases was 1 event every 42 surgical
      cases and 1 permanent neurologic deficit every 573 cases. CONCLUSION: The
      combined use of somatosensory-evoked potentials, transcranial electric motor
      evoked potentials, descending neurogenic-evoked potentials, and electromyography
      monitoring allowed accurate detection of permanent neurologic status in 99.6% of
      3436 patients and reduced the total number of permanent neurologic injuries to 6.

PMID- 20802389
TI  - Tissue transglutaminase expression and activity in human ligamentum flavum cells
      derived from thoracic ossification of ligamentum flavum.
AB  - STUDY DESIGN: The study was undertaken to compare the expression and activity of
      tissue transglutaminase (TG2) in human ligamentum flavum cells derived from
      ossification of the ligamentum flavum (OLF) and non-OLF patients. OBJECTIVE: To
      determine whether TG2 is involved in the pathologic process of OLF. SUMMARY OF
      BACKGROUND DATA: OLF is a disease characterized by heterotopic formation of new
      bone in the flavum ligament. Recently, TG2 is proved to directly promote skeletal
      matrix mineralization and play an important role in the ossification. TG2
      activity is vital to the differentiation of osteoblasts and the formation of
      mineralization. But whether TG2 is involved in the pathologic process of OLF is
      unknown. We investigated the relations between TG2 expression and OLF. METHODS:
      OLF and non-OLF cells were cultured and osteocalcin, bone morphogenetic protein
      2(BMP-2) and TG2 mRNA expressions were assayed by reverse transcription
      polymerase chain reaction. Meanwhile, alkaline phosphatase activity and calcified
      nodules were compared between OLF and non-OLF cells. To detect TG2 expression,
      Western blot and immunohistochemical analysis were carried out, and TG2 activity
      was compared between OLF and non-OLF cells. RESULTS: Our experiments demonstrated
      that OLF cells showed osteoblast-like activity and increased mRNA expression of
      BMP-2. More interesting, compared with non-OLF cells, OLF cells showed elevated
      expression levels of TG2 mRNA and protein, as well as enzyme activity.
      CONCLUSION: TG2 expression and enzyme activity are upregulated in the OLF cells
      and TG2 may be involved in the pathologic process of OLF.

PMID- 20802390
TI  - Low profile pelvic fixation with the sacral alar iliac technique in the pediatric
      population improves results at two-year minimum follow-up.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: Anchor stability and prominence
      are problems with pelvic fixation in pediatric spinal deformity surgery. We
      compared the new sacral alar iliac (SAI) fixation technique (with a starting
      point in the sacral ala and in-line anchors deep under the midline muscle flap)
      with other methods of screw fixation. SUMMARY OF BACKGROUND DATA: Iliac anchors
      have been shown to provide the best form of pelvic fixation. A trajectory from
      the posterior sacral surface to the iliac wings has recently been described. To
      our knowledge, no clinical series has compared this method of pelvic fixation in
      children to others. METHODS: Of 32 consecutive pediatric patients who underwent
      SAI fixation, 2 died and 26 returned for follow-up (>2 years). Mean age at
      surgery was 14 years. Average screw size was 67 mm long and 7 to 9 mm in
      diameter. Clinical examinations, radiographs, and computed tomography scans were
      analyzed. Outcomes included pain over the implants, screw placement, implant
      prominence, radiographic lucency, need for revision, and infection. SAI patients
      were compared with 27 previous patients who had pelvic fixation via other screw
      techniques. RESULTS: For SAI fixation, correction of pelvic obliquity and Cobb
      angles were 20 degrees  +/- 11 degrees  (70%) and 42 degrees  +/- 25 degrees 
      (67%), respectively. For other pelvic fixation methods, those values were 10
      degrees  +/- 9 degrees  (50%), and 46 degrees  +/- 16 degrees  (60%),
      respectively. Compared with other screws, SAI screws provided significantly
      better pelvic obliquity correction (P = 0.002) but no difference in Cobb
      correction. There were 2 lucencies adjacent to screws in both groups. Computed
      tomography scans of 18 SAI patients showed no intrapelvic protrusion, but 1 screw
      extended laterally (<5 mm). One early SAI patient required revision with larger
      screws, which relieved pain; there was 1 revision in the comparison group. SAI
      patients had no deep infections, implant prominence, late skin breakdown, or
      anchor migration; traditional patients had 3 deep infections (P = 0.09) and 3
      instances of implant prominence, skin breakdown, or anchor migration. CONCLUSION:
      SAI pelvic fixation produces better correction of pelvic obliquity than do
      previous techniques. Radiographic and clinical anchor stability is satisfactory
      at 2-year follow-up.

PMID- 20802391
TI  - Extension of prior idiopathic scoliosis fusions to the sacrum: a matched cohort
      analysis of sixty patients with minimum two-year follow-up.
AB  - STUDY DESIGN: Comparative study. OBJECTIVE: To compare the radiographic and
      clinical outcomes of patients undergoing extension of a previous idiopathic
      scoliosis fusion to the sacrum using either autogenous bone graft or recombinant
      human bone morphogenetic protein-2 (rhBMP-2). SUMMARY OF BACKGROUND DATA:
      Extension of an existing idiopathic scoliosis fusion to the sacrum for distal
      degeneration or sagittal imbalance has been associated with a high rate of
      pseudarthrosis. We hypothesized that rhBMP-2 could be successfully used as a
      substitute for distant autograft in this challenging population. METHODS:
      Consecutive patients were identified from a single institution prospective
      database. The control group (autogenous harvesting without rhBMP-2, 1998-2002)
      included 24 of 25 patients with minimum 2-year follow-up while the study group
      (rhBMP-2 without distant autograft, 2002-2006) included 36 of 39 patients with
      minimum 2-year follow-up. Radiographs were measured using standard adult
      deformity criteria. Fusions were evaluated by independent observers using a
      published 4-point scale. Clinical outcomes were evaluated using Scoliosis
      Research Society and Oswestry Disability Index Questionnaires. RESULTS: Groups
      were well matched with respect to demographic, radiographic, and surgical data
      with the following exceptions: the control group (autogenous graft, no BMP) was
      younger (43.5 vs. 49.8 years; P = 0.04), had more anterior levels fused (3.3 vs.
      1.7; P = 0.01), more thoracoabdominal approaches (25% vs. 2.7%; P = 0.01), and
      greater estimated blood loss (1938 vs. 1221 mL; P = 0.01). There was 1 wound
      complication (deep infection) in each group. Rates of radiographic pseudarthrosis
      (11.1% vs. 20.8%) and revision for pseudarthrosis (5.6% vs. 12.5%) were lower in
      the rhBMP-2 group, although this did not reach statistical significance.
      Preoperative, postoperative, and improvements in Scoliosis Research Society and
      Oswestry Disability Index scores were similar between groups. We did not observe
      any increase in adverse events with the use of rhBMP-2. CONCLUSION: BMP-2 is a
      safe and effective alternative to iliac or rib harvesting when extending an
      existing idiopathic scoliosis fusion to the sacrum.

PMID- 20802392
TI  - A new look at the geometry of the lumbar spine.
AB  - STUDY DESIGN: A retrospective cohort study of the relationship between the
      structures that form the lumbar spine in humans. OBJECTIVE: To investigate the
      relationship between the segmental wedging of the vertebral bodies and that of
      the intervertebral discs, and between the overall lordosis angle and each of the
      5 lumbar segments. SUMMARY OF BACKGROUND DATA: Little attention has been paid to
      the internal relationship between the structures that form the lumbar spine.
      Understanding these relationships is instrumental to our ability to restore and
      rehabilitate the lordotic curvature. METHODS: Lateral radiographs of 101 adult
      lumbar spines were examined in patients at spinal clinics. The patients had no
      history of spinal surgery and no radiographic abnormality. The radiologic
      parameters are the lordosis angle (LA), the body wedge angle (B), the total
      segmental angle (S), and the intervertebral disc angle (D). Measurements B, S,
      and D were taken for each of the 5 lumbar segments. Measurements B and D were
      used to calculate SigmaB, the sum of the B, and SigmaD, the sum of the D.
      RESULTS: The LA correlates with the sum of the vertebral body angles and with the
      sum of the intervertebral disc angles. Vertebral body wedging is negatively
      correlated with intervertebral disc wedging. The middle 3 lumbar segments are
      moderately-to-poorly correlated, among themselves and with the LA, while the
      upper and lower lumbar segments are poorly correlated with the LA and not
      correlated with any lumbar segment. CONCLUSION: Three parts of the lumbar
      lordosis were identified: the upper part, formed by the first lumbar segment; the
      middle part, formed by the middle 3 segments; and the lower part, formed by the
      fifth lumbar segment. The statistical study shows an inverse relationship between
      vertebral body and intervertebral disc wedging.

PMID- 20802393
TI  - A clinical comparative study on low versus medium viscosity polymethylmetacrylate
      bone cement in percutaneous vertebroplasty: viscosity associated with cement
      leakage.
AB  - STUDY DESIGN: Comparative, prospective follow-up study. OBJECTIVE: Comparison of
      outcome between patients treated with Percutaneous VertebroPlasty (PVP) using low
      and medium viscosity PolyMethylMetAcrylate (PMMA) bone cement. SUMMARY OF
      BACKGROUND DATA: Viscosity is the characterizing parameter of PMMA bone cement,
      currently the standard augmentation material in PVP, and influences
      interdigitation, cement distribution inside the vertebral body, injected volume
      and extravasation, thereby affecting the clinical outcome of PVP. Currently, low,
      medium, and high viscosity PMMA bone cements are used interchangeably. However,
      effect of viscosity on clinical outcome in patients with Osteoporotic Vertebral
      Compression Fractures (OVCFs) has not yet been explicit subject of investigation.
      METHODS: Follow-up was conducted using a 0 to 10 Pain Intensity Numerical Rating
      Scale (PI-NRS) and the Short Form 36 (SF-36) Quality of Life questionnaire before
      PVP and at 7 days (PI-NRS only), 1, 3, and 12 months after PVP. Injected cement
      volume, degree of interdigitation, and cement leakage were analyzed on direct
      postoperative computed tomography scanning. At 6 and 52 weeks and at suspicion,
      patients were analyzed for new fractures. RESULTS: A total of 30 consecutive
      patients received PVP using low viscosity PMMA bone cement (OsteoPal-V) for 62
      OVCFs, followed by 34 patients who received PVP using medium viscosity PMMA bone
      cement (Disc-O-Tech) for 67 OVCFs. Results regarding PI-NRS and SF-36 were
      comparable between both groups. Postoperative comparison of injected cement
      volume, degree of interdigitation, proportion of bipedicular procedures,
      incidence of new vertebral fractures and complications revealed no differences
      between both groups. Viscosity was identified as a risk factor for the occurrence
      of cement leakage (yes/no, OR: 2.925, 95% confidence interval: [1.072-7.984], P =
      0.036). CONCLUSION: No major differences in clinical outcome after PVP in OVCFs
      using low and medium viscosity PMMA bone cement were found. Viscosity of PMMA
      bone cement was identified as an independent predictor of cement leakage.

PMID- 20802394
TI  - The transfer of disc pressure to adjacent discs in discography: a specificity
      problem?
AB  - STUDY DESIGN: In vivo experimental study. OBJECTIVE: The primary objective of the
      study was to investigate pressure transmission to adjacent discs during
      discography. A secondary objective was to quantify the transmitted pressure, both
      in contrast injected and noninjected porcine intervertebral discs. SUMMARY OF
      BACKGROUND DATA: Discography is used to before surgery identify painful discs. A
      pain response during discography that is concordant with the patient's
      experienced back pain is regarded as an indication that the injected disc is the
      source of pain. However, the sensitivity and specificity of discography are
      matters of debate. Pressure-controlled discographies have been reported to reduce
      the number of false-positive discs using low pressure criteria. Preliminary data
      indicated a transfer of pressure from an injected to an adjacent disc during
      discography. Pressure transmission in vivo during lumbar discography, not
      reported before might, if clinically present, contribute to a false-positive
      diagnosis. METHODS: Thirty-six lumbar discs in 9 adolescent pigs were
      investigated. Intradiscal pressure was recorded during contrast injection, using
      a 0.36/0.25 mm fiber-optic pressure transducer inserted into the nucleus pulposus
      via a 22 G needle. The pressure was measured simultaneously in 2 adjacent discs
      during contrast injection into 1 of the discs at pressures up to 8 bar.
      Transmitted pressure was recorded both in noninjected discs and in discs that
      were prefilled with contrast. RESULTS: Thirty-three discs were successfully
      examined. During contrast injection, there was an intradiscal pressure rise in
      the adjacent disc with a median value of 16.0% (range, 3.2-37.0) over baseline
      pressure. There was no significant difference in pressure increase between the
      noninjected and prefilled discs (P < 0.68). CONCLUSION: Discography of porcine
      discs induces a pressure increase in adjacent discs. A similar pressure transfer
      during human clinical discography might elicit false-positive pain reactions.

PMID- 20802395
TI  - Metastatic epithelioid trophoblastic tumor involving the spine.
AB  - STUDY DESIGN: This is a single case-based report. OBJECTIVE: We report the first
      case of epithelioid trophoblastic tumor (ETT) presenting as primary metastasis to
      the spine. SUMMARY OF BACKGROUND DATA: ETT is an extremely rare form of
      gestational trophoblastic neoplasm with less than 100 cases reported in the
      literature. A 36-year-old, postpartum woman presented with severe low back pain
      and was found to have a contrast-enhancing lesion in lower thoracic spine
      subsequently confirmed as ETT. METHODS: The patient data, history, clinical
      examination findings, laboratory, and histopathology data and imaging studies
      were retrospectively reviewed and findings reported. A literature search using
      Pubmed and Cochrane database was conducted. RESULT: We described the first case
      of an ETT to present as a primary metastasis to the spine. CONCLUSION: This first
      report of metastasis of ETT to the spine adds significant new information to the
      growing literature of this rare and newly identified tumor. It also alerts the
      neurosurgeon into considering the diagnosis with appropriate clinical
      presentation. As more number of cases of nervous system involvement with this
      tumor are reported, crucial information on prognostic factors and treatment
      regimens will emerge.

PMID- 20802396
TI  - Right thoracic curves in presumed adolescent idiopathic scoliosis: which clinical
      and radiographic findings correlate with a preoperative abnormal magnetic
      resonance image?
AB  - STUDY DESIGN: Prospective case control study. OBJECTIVE: This study investigated
      preoperative presumed adolescent idiopathic scoliosis (AIS) patients with right
      thoracic curves to determine which clinical and radiographic findings correlate
      with neural axis abnormalities on magnetic resonance imaging (MRI). SUMMARY OF
      BACKGROUND DATA: Neural axis abnormalities on MRI are not uncommon in patients
      with left thoracic curves, increased thoracic kyphosis, and in children less than
      10 years old. For adolescents with right thoracic curves, less is known regarding
      which clinical and/or radiographic characteristics accompany neural axis
      abnormalities. METHODS: A total of 529 presumed AIS patients with Lenke 1-4 right
      thoracic curve patterns had MRI evaluation before surgery. Thirty-six of these
      patients had abnormal MRIs (syrinx, Chiari malformation, and/or tethered cord).
      To differentiate between those with normal MRIs (n = 493) and those with abnormal
      MRIs (n = 36), the following preoperative clinical parameters were evaluated:
      age, gender, height, weight, asymmetric abdominal reflexes, thoracic rotation
      (scoliometer), coronal balance, trunk shift, shoulder elevation, and the
      Scoliosis Research Society (SRS)-30 questionnaire. Radiographically, thoracic
      curve magnitude, thoracic rotation (Nash-Moe), coronal balance, trunk shift,
      length of thoracic curve, location of curve apex, sagittal balance, thoracic
      kyphosis (T2-T12), and lumbar lordosis were evaluated. RESULTS: Neural axis
      abnormalities were found in 6.8%. Those with abnormal MRI findings had
      significantly greater clinical thoracic rotation (mean difference, 2.4 degrees )
      and significantly greater radiographic thoracic kyphosis (mean difference 5.9
      degrees ). However, there were no significant differences in: age (14.9 vs. 14.7
      years), height for age (when adjusted for gender), asymmetric abdominal reflexes
      (3.5% normal MRI group vs. 6.1% abnormal group), coronal balance (clinical or
      radiographic), trunk shift(clinical or radiographic), shoulder elevation,
      thoracic curve magnitude (61.4 degrees  normal MRI group vs. 63.6 degrees 
      abnormal group), length of thoracic curves (7.0 segments normal group vs. 7.2
      segments abnormal group), location of curve apexes, radiographic sagittal
      balance, or any domains of the preoperative SRS-30 questionnaire. CONCLUSION: Of
      preoperative presumed AIS patients with right thoracic curves who underwent MRI
      evaluation of the neural axis, 6.8% were found to have neural axis abnormalities,
      with those having increased rotation and/or increased kyphosis at higher risk.
      Surgeons should use this information when deciding whether a preoperative MRI is
      indicated in those with right thoracic AIS curve patterns.

PMID- 20802397
TI  - A novel pedicle channel classification describing osseous anatomy: how many
      thoracic scoliotic pedicles have cancellous channels?
AB  - STUDY DESIGN: Prospective clinical series. OBJECTIVE: To determine how many
      thoracic scoliotic pedicles have cancellous versus cortical versus absent
      channels. SUMMARY OF BACKGROUND DATA: Although morphologic evaluations of
      thoracic pedicles have been well reported, the results do not practically reflect
      clinical findings during actual pedicle screw placement. We propose a novel
      pedicle channel classification describing the osseous anatomy encountered during
      pedicle probe insertion. METHODS: We noted 4 pedicle types in 53 consecutive
      scoliosis patients. Type A: pedicle probe smoothly inserted without difficulty;
      the morphology is described as a "Large Cancellous Channel." Type B: pedicle
      probe inserted snugly with increased force; described as a "Small Cancellous
      Channel." Type C: pedicle probe cannot be manually pushed but must be tapped with
      a mallet down the pedicle into the body; described as a "Cortical Channel." Type
      D: pedicle probe cannot locate a channel thus necessitating a "juxtapedicular"
      screw position; described as a "Slit/Absent Channel." The average age at time of
      surgery was 23.4 +/- 16.7 years. Diagnoses included idiopathic scoliosis (n = 38)
      and syndromic scoliosis (n = 15). The average main thoracic Cobb angle was 73
      degrees  +/- 26 degrees . Evaluation of pedicle morphology of the 4 types was
      also performed in 21 consecutive cases of adolescent idiopathic scoliosis using
      preoperative computed tomography images. RESULTS: A total of 1021 pedicles with
      screws placed were evaluated. The average percent per type was as follows: 61.0%
      type A; 29.2% type B, 6.8% type C, and 3.0% type D. On the convexity, 98.2% of
      pedicles were type A or B versus 81.5% on the concavity (P < 0.05). There were
      significant differences between adolescent versus adult idiopathic scoliosis (P =
      0.007), and syndromic scoliosis versus adult idiopathic scoliosis (P = 0.017)
      regarding pedicle morphologic proportions. There was a significant tendency
      toward a decrease in the proportion of type A pedicles, an increase in the
      proportion of type B pedicles as the Cobb angle increased (P < 0.0001).
      Evaluation based on 312 thoracic pedicles in 21 consecutive adolescent idiopathic
      scoliosis patients using preoperative computed tomography axial images confirmed
      assumptions of the 4 pedicle types. CONCLUSION: We propose a classification for
      pedicle channels describing the osseous anatomy encountered during pedicle probe
      insertion. Based on the classification, surprisingly, we found during surgery
      that 90% of thoracic pedicles had a cancellous channel, whereas 7% had a cortical
      channel and only 3% had an absent channel.

PMID- 20802398
TI  - Surgical outcomes of decompression, decompression with limited fusion, and
      decompression with full curve fusion for degenerative scoliosis with
      radiculopathy.
AB  - STUDY DESIGN: A retrospective clinical cohort study at a single spine center of
      patients with degenerative scoliosis and radiculopathy severe enough to require
      surgery. OBJECTIVE: To evaluate the functional outcomes of 3 surgeries for
      degenerative scoliosis with radiculopathy; decompression alone, decompression and
      limited fusion, and decompression and full curve fusion. SUMMARY OF BACKGROUND
      DATA: Although these 3 surgical treatments have all been described for this
      problem, there exists little information as to what outcomes to expect. METHODS:
      The study cohort consisted of 85 patients who met the inclusion criteria of
      degenerative scoliosis and radiculopathy, who had undergone 1 of the above 3
      surgeries, who had not had any previous lumbar spine surgery, who had a minimum
      follow-up of at least 2 years, and who had filled out preoperative and
      postoperative functional evaluation forms including SF-36, Oswestry Disability
      Index, Roland Morris Scores, and a satisfaction questionnaire. Logistic
      regression analysis was conducted to predict the likelihood of success as related
      to decompression alone of rotatory olisthetic segments, extent of fusion, and
      postoperative sagittal balance. Patient demographics including curve magnitude,
      operative blood loss, length of hospital stay, complications, and need for
      revision surgeries were analyzed. The patients having decompression alone had the
      highest mean age (76.4 years) compared to decompression and limited fusion
      (70.4), and decompression and full curve fusion (62.5). RESULTS: Cobb scoliosis
      angles remained unchanged in the 2 groups not having full curve fusion, while the
      full curve fusion group changed from a mean 39 degrees  before surgery to 19
      degrees  at follow-up. The complication rate was highest (56%) in the full fusion
      group, was 40% in the limited fusion group, and 10% in the decompression alone
      group. The overall SF-36 analysis showed significant improvement in bodily pain,
      social function, role emotional, mental health, and mental composite domains.
      Oswestry Disability Indexes improved significantly in the decompression alone and
      limited fusion groups, but not in the full fusion group. In contrast, the
      satisfaction questionnaire showed the highest success to be in the full-curve
      fusion group and the lowest in the decompression-only group.Regression analysis
      revealed that sacrum to curve apex fusions and positive postoperative sagittal
      imbalance were associated with poor outcomes. CONCLUSION: Both good and poor
      results were seen with each of the 3 procedures.

PMID- 20802399
TI  - Rapid engraftment at a cost?

PMID- 20802400
TI  - Identification of MHC II-restricted minor histocompatibility antigens after HLA
      identical stem-cell transplantation.
AB  - BACKGROUND: After allogeneic hematopoietic stem-cell transplantation (HSCT),
      donor-derived T cells may elicit graft-versus-host disease (GVHD) and graft
      versus-tumor (GVT) responses. The main targets of GVHD and GVT responses after
      human leukocyte antigen (HLA)-identical HSCT are minor histocompatibility
      antigens (mHAgs), that is, polymorphic gene products in which recipient and donor
      differ. Thus, for increasing beneficial GVT and decreasing life-threatening GVHD
      responses, knowledge of the relevant mHags is required. Here, we sought to
      identify mHags recognized by CD4 T cells using a novel serologic approach.
      METHODS: To identify candidate mHAgs recognized by CD4 T cells, a cDNA expression
      library from peripheral blood mononuclear cells of a patient with beta
      thalassemia major was screened with serum taken at different time points after
      HLA-identical HSCT. RESULTS: Immune responses against 18 antigens were identified
      with serum taken 100 days posttransplantation, when the patients had recovered
      from acute GVHD II. Except for one, no humoral responses against these antigens
      were detected 25 days or 1 year after transplantation. Sequence comparison of
      these antigens between recipient and donor revealed three polymorphisms of which
      two were contained within epitopes predicted to bind to HLA-DR molecules of the
      patient. Using cytokine secretion and capture assays, T cells specific for the
      polymorphic antigens of the recipient, but not the donor, were isolated from
      peripheral blood monocyte cells after HSCT. CONCLUSIONS: The serologic approach
      described here facilitates the rapid identification of mHAgs recognized by CD4 T
      cells. Furthermore, the correlation of humoral and cellular immune responses with
      acute GVHD implies a role of these antigens in GVHD pathology.

PMID- 20802401
TI  - Cytotoxic tirucallane triterpenoids from Melia azedarach fruits.
AB  - The phytochemical investigation of the dichloromethane-soluble part of the
      methanol extract obtained from the fruits of Melia azedarach afforded one new
      tirucallane-type triterpene, 3-alpha-tigloylmelianol and three known
      tirucallanes, melianone, 21-beta-acetoxy-melianone, and methyl kulonate. The
      structure of the isolated compounds was mainly determined by 1D and 2D NMR
      experiments as well as HPLC-Q-TOF mass spectrometry. The cytotoxicity of the
      isolated compounds toward the human lung adenocarcinoma epithelial cell line A549
      was determined, while no activity was observed against the phytonematode
      Meloidogyne incognita.

PMID- 20802403
TI  - Modular synthesis of polyphenolic benzofurans, and application in the total
      synthesis of malibatol a and shoreaphenol.
AB  - A modular strategy for the synthesis of hexacyclic dimeric resveratrol
      polyphenolic benzofurans is reported. The developed synthetic technology was
      applied to the total synthesis of malibatol A, shoreaphenol, and other
      biologically relevant poly-phenols.

PMID- 20802402
TI  - Discovery and development of anti-HBV agents and their resistance.
AB  - Hepatitis B virus (HBV) infection is a prime cause of liver diseases such as
      hepatitis, cirrhosis and hepatocellular carcinoma. The current drugs clinically
      available are nucleot(s)ide analogues that inhibit viral reverse transcriptase
      activity. Most drugs of this class are reported to have viral resistance with
      breakthrough. Recent advances in methods for in silico virtual screening of
      chemical libraries, together with a better understanding of the resistance
      mechanisms of existing drugs have expedited the discovery and development of
      novel anti-viral drugs. This review summarizes the current status of knowledge
      about and viral resistance of HBV drugs, approaches for the development of novel
      drugs as well as new viral and host targets for future drugs.

PMID- 20802404
TI  - An efficient procedure based on a MW-assisted Horner-Wadsworth-Emmons reaction
      for the synthesis of (Z)-3,3-trisubstituted-alpha,beta-unsaturated esters.
AB  - A microwave-assisted HWE olefination process of readily accessible aryl-alkyl
      ketones has been developed to provide a rapid access to (Z)-3,3-trisubstituted
      alpha,beta-unsaturated methyl esters, key building blocks for the synthesis of
      biologically active compounds.

PMID- 20802405
TI  - MALDI mass spectrometry imaging of proteins exceeding 30,000 daltons.
AB  - BACKGROUND: Since its introduction 10 years ago by Caprioli and associates, MALDI
      mass spectrometry imaging has enabled spatial analysis of drugs, lipids,
      peptides, and polypeptides. In polypeptides, the detectable mass range is limited
      to small proteins with a mass less than 25 kDa. This is a limitation, as many
      proteins, including cytokines, growth factors, enzymes, and receptors have
      molecular weights, exceeding 25 kDa. In the present work, we report the
      development of a novel strategy to observe higher mass proteins up to 30 kDa.
      MATERIAL/METHODS: We investigated the development of sample preparation methods
      based on hexafluoroisopropanol (1,1,1,3,3,3-hexaluoro-2-propanol) and 2,2,2
      trifluoroethanol solvents for protein solubilization optimized for high-mass
      proteins. RESULTS: We were, for the first time in mass spectrometry imaging, able
      to detect to proteins up to 70 kDa directly from tissue. These developments
      indicate future avenues by which the sensitivity of protein mass spectrometry
      imaging can be further improved. We applied these developments to ovarian cancer
      and demonstrate that protein are similar to that which can be obtained using 2D
      gel based analyses. CONCLUSIONS: Increasing the possibility of detecting proteins
      and high-mass proteins is key for developing direct tissue proteomics and
      especially any potential functional investigation. These data will open the door
      of a novel step in mass spectrometry imaging.

PMID- 20802406
TI  - Cytosolic phospholipase A2 group IVA influence on GM-CSF expression in human lung
      cells: a pilot study.
AB  - BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an
      important mediator in the differentiation, maturation, and survival of
      inflammatory cells. It might play a significant role in the pathogenesis of
      asthma. We have shown previously that cytosolic phospholipase A2 group IV A
      (cPLA2alpha) is able to activate gene expression, through peroxisome proliferator
      activated receptor (PPAR)-gamma response elements (PPRE). In the promoter regions
      of GM-CSF gene (CSF2), we have found potential PPRE. The goal of the current
      study was to investigate the influence of cPLA2 overexpression and activation on
      CSF2 gene expression in human lung cells. MATERIAL/METHODS: Subconfluent A549
      cells were transfected with GM-CSF reporter gene and cPLA2alpha overexpression
      vector. Transfected cells were treated with or without calcium ionophore, A23187,
      or epidermal growth factor (EGF). Cell lysates were collected and assayed for
      dual luciferase activity. Some cultures were preincubated with a potent
      cPLA2alpha inhibitor, methyl arachidonyl fluorophosphonate (MAFP); a secretory
      phospholipase A2 inhibitor, thioetheramide-PC; a calcium-independent
      phospholipase A2 inhibitor, bromoenol lactone (BEL); or vehicle. After
      preincubation, cells were treated with A23187. Expression of GM-CSF messenger RNA
      (mRNA) was measured using real-time polymerase chain reaction mRNA
      quantification. RESULTS: Overexpression of cPLA2alpha or activation of endogenous
      cPLA2alpha by calcium ionophore or EGF caused a significant increase in GM-CSF
      relative luciferase activity. Calcium ionophore significantly increased GM-CSF
      mRNA in A549 human lung cells. These effects were at least in part inhibited by
      MAFP treatment, but not by BEL or thioetheramide-PC. CONCLUSIONS: These
      preliminary data might suggest an influence of cPLA2alpha on GM-CSF gene
      expression in human lung cells, which could play a role in the pathogenesis of
      asthma and other inflammatory diseases.

PMID- 20802407
TI  - The protective action of topiramate on dopaminergic neurons.
AB  - BACKGROUND: The present study analyzed the neuroprotective effects of topiramate
      on 6-hydroxydopamine (6-OHDA)-induced toxicity in primary dopaminergic
      mesencephalic neuronal cell cultures. MATERIAL/METHODS: Through the use of
      tyrosine hydroxylase and microtubule-associated protein 2 immunocytochemistry,
      the morphology and development of dopaminergic neurons was observed. Hoechst33258
      and propidium iodide (PI) double staining was used to determine cell membrane
      penetrability and apoptosis by fluorescent microscopy. Methyl thiazole
      tetrazolium was used to assay cell viability and metabolism. The cells were
      assigned to 3 groups: (1) control: primary cultured neurons; (2) 6-OHDA: primary
      cultured neurons and 6-OHDA; and (3) topiramate (TPM) protection: primary
      cultured neurons and 6-OHDA, treated with various concentrations (10, 50, and 100
      microM) of TPM. RESULTS: Hoechst 33258 and PI double immunofluorescence revealed
      that the number of dying cells after 6-OHDA treatment was greater than after TPM
      treatment. Compared with the 6-OHDA group, there were more neurons with greater
      cell viability in the 6-OHDA plus TPM group. CONCLUSIONS: Topiramate was shown to
      provide protection to dopaminergic neurons exposed to 6-OHDA by reducing cell
      apoptosis and enhancing cell viability. The neuroprotective effects of TPM were
      dose-dependent.

PMID- 20802408
TI  - Evaluation of lymphatic function by means of dynamic Gd-BOPTA-enhanced MRL in
      experimental rabbit limb lymphedema.
AB  - BACKGROUND: The aim of this study was to investigate the value and technical
      methods of 3D dynamic contrast-enhanced magnetic resonance lymphangiography (MRL)
      in the assessment of lymphatic anatomy and function in the presence of extremity
      lymphedema. MATERIAL/METHODS: An improved experimental model of obstructive
      lymphedema was established in 1 hind limb of 6 New Zealand White rabbits. 3D
      contrast-enhanced MRL was performed with a 3.0-T MR unit after the intracutaneous
      injection of Gd-BOPTA into the interdigital webs of the dorsal paws. Maximum
      intensity projection (MIP) was used to reconstruct the images of the lymphatic
      system. The dynamic nodal enhancement in the popliteal fossa and time-signal
      intensity curves between lymphedematous and contralateral limbs were compared.
      Morphologic abnormalities of the lymphatic system were also evaluated and
      compared with lymphoscintigraphy (LSG). RESULTS: 3D dynamic contrast-enhanced MRL
      images were obtained after the administration of Gd-BOPTA. In the normal limb,
      the popliteal fossa lymph nodes and their afferent and efferent lymph-collecting
      vessels were clearly visualized as the Gd tracer was rapidly cleared from the
      interstitial compartment. In contrast, the Gd tracer accumulated slowly at the
      prior surgical site in the lymphedematous limb. The nodal enhancement of
      lymphedematous limbs was significantly less than that of the contralateral limbs
      (P<0.01). Types of time-signal intensity curves were also significantly different
      between the 2 groups (P<0.001). CONCLUSIONS: 3D dynamic contrast-enhanced MRL can
      visualize the precise anatomy of lymphatic vessels and lymph nodes in extremity
      lymphedema, as well as objectively evaluate the functional status of lymph flow
      transport.

PMID- 20802409
TI  - Melatonin and childhood refractory epilepsy--a pilot study.
AB  - BACKGROUND: The aim of the study was to assess diurnal melatonin secretion in
      children with refractory epilepsy (N=74) as compared to children without
      epileptic seizures (N=37) and to compare melatonin secretion in children with
      focal and generalized refractory epilepsy. MATERIAL/METHODS: In the study group 4
      subgroups were defined: children with focal symptomatic epilepsy, focal
      cryptogenic epilepsy, generalized symptomatic epilepsy, and generalized
      cryptogenic epilepsy. Melatonin level was measured every 3 hours using the RIA
      method. RESULTS: Analysis of diurnal melatonin secretion indicated a lower level
      of the hormone in patients with refractory epilepsy. The daily rhythm of
      melatonin secretion in the study group was maintained, with a peak shift of
      melatonin secretion especially visible in the subgroup with generalized
      symptomatic refractory epilepsy in the age group between 6 months and 3 years of
      age. CONCLUSIONS: The hypothesis may be formed that a lowered level of melatonin
      in the study group in relation to the comparison group is the consequence of the
      natural course of epilepsy or is influenced by antiepileptic drugs.

PMID- 20802410
TI  - Impact of reversible myocardial ischaemia on nitric oxide and asymmetric
      dimethylarginine production in patients with high risk for coronary heart
      disease.
AB  - BACKGROUND: The aim of the present study was to assess the impact of reversible
      myocardial ischemia, provoked by acute physical activity during an exercise
      stress echocardiography (ESE), on nitric oxide (NOx) and asymmetric
      dimethylarginine (ADMA) production in patients with high risk for coronary heart
      disease (CHD). MATERIAL/METHODS: An overall of 45 patients (27 men, 18 women;
      mean age, 55.87+/-6.39 years), was enrolled in the study and assigned into groups
      according to sex, CHD risk factors (RF), wall motion score (WMS), and diabetes
      mellitus (DM). An ESE was performed on an ergocycle, using a standardized
      protocol. The modified Saville-Griess method was used to determine NOx
      concentration. Production of ADMA was evaluated by high-performance liquid
      chromatography with fluorescent detection. RESULTS: A significant increase of NOx
      was observed in men (P<.05) and patients with stable WMS (P<.01), as well as its
      decrease in patients with increased WMS, whereas ADMA significantly increased in
      both sexes (P<.001 and P<.01 in men and women, respectively), independently of
      CHD risk (P<.05 and P <.001 in 1-2 RF and > or =3 RF groups, respectively),
      presence of DM (P<.001 and P<.01 in no-DM and DM groups, respectively), and WMS
      dynamic (P<.05 and P<.001 in WMS stable and WMS increased groups, respectively).
      The WMS was significantly higher in the > or =3 RF group (P<.01) after ESE and
      significantly increased in both sexes (P<.001 and P<.01 in men and women,
      respectively), with no regard to DM (P<.001 and P<.01 in no-DM and DM groups,
      respectively). CONCLUSIONS: The results of the present study clearly demonstrated
      a significant increase of NOx in patients with stable WMS and its decrease in
      patients with increased WMS after ESE, compared with the resting condition, as
      well as a significant increase of ADMA both in patients with stable WMS and those
      with increased WMS, irrespective of sex and CHD risk. A significant increase of
      WMS was observed in the > or =3 CHD RF group, in both sexes, with no regard to
      the presence of DM.

PMID- 20802411
TI  - Influence of salivary secretory immunoglobulin A level on the pain experienced by
      orthodontic patients.
AB  - BACKGROUND: Pain, a common experience reported by patients under orthodontic
      treatment, results from force application to the teeth and trauma caused by
      attrition of brackets and wires against the underlying oral mucosa. The main
      protection of the mucosa is secretory immunoglobulin A (sIgA), which may play a
      fundamental role in integrity maintenance and whose production may be reduced as
      a result of the stress of orthodontic treatment. The aim of this study was to
      assess sIgA levels in the saliva and their correlation with oral pain intensity
      in adults and children after the installation of fixed orthodontic appliances.
      MATERIAL/METHODS: Twenty patients (10 children, age 11-13 years; 10 adults, age
      18-37 years) were assessed before treatment, after bracket bonding, and after
      initial arch wire insertion. Saliva was sampled for sIgA analysis, and oral pain
      was assessed through a visual analog scale. RESULTS: Although there was a trend
      toward reduction of the salivary sIgA levels during the initial arch phase in the
      children, and during the bonding and initial arch phases in the adults, this
      finding was not significant. CONCLUSIONS: There was a trend toward a negative
      correlation of oral pain intensity and salivary sIgA levels in the children,
      which may indicate the importance of sIgA for oral protection during orthodontic
      treatment, interfering with the pain experienced by the patients.

PMID- 20802412
TI  - Detection of aberrant p16INK4A methylation in sera of patients with HCV-related
      liver diseases: An Egyptian study.
AB  - BACKGROUND: The present study was performed to estimate the frequency of
      methylated p16INK4A in the sera of patients with hepatitis C virus (HCV)-related
      chronic active hepatitis (CAH), liver cirrhosis (LC), and hepatocellular
      carcinoma (HCC) and to evaluate the role of p16INK4A as a tumor marker of HCC.
      MATERIAL/METHODS: The sera of 17 CAH, 20 LC, and 25 HCC patients were examined in
      this study. The methylation status of p16INK4A was evaluated by methylation
      specific PCR of the serum samples. RESULTS: Methylated p16INK4A was detected in
      47.1% (8/17) of the CAH patients, 5% (4/20) of the LC patients, and in 92%
      (23/25) of the HCC patients. HBV markers were detected in (4/25) of HCC patients;
      all had methylated p16INK4A. No association was demonstrated between p16INK4A
      methylation and serum AFP level in the HCC group. CONCLUSIONS: The results of
      this study indicate that aberrant DNA methylation contributes to
      hepatocarcinogenesis and it may be an early event during hepatocarcinogenesis. As
      the status of p16INK4A methylation was not associated with serum AFP level, it
      may have a complementary role with AFP as a tumor marker of HCC.

PMID- 20802413
TI  - Comparison of primary percutaneous coronary intervention and streptokinase for
      acute isolated inferior ST elevation myocardial infarction with a predicted low
      risk profile.
AB  - BACKGROUND: Primary percutaneous coronary intervention (PCI) is the treatment of
      choice for acute myocardial infarction, especially for high-risk patients, but
      the data for low-risk patients are conflicting. A very low-risk subgroup of acute
      inferior myocardial infarction can be identified by electrocardiographic and
      clinical criteria during admission. We aimed to compare the outcomes of primary
      PCI and streptokinase treatment in this subgroup, which has not been evaluated
      separately before. MATERIAL/METHODS: We retrospectively analyzed in-hospital and
      10-month follow-up outcomes of 97 patients with inferior acute myocardial
      infarction and clinical and electrocardiographic criteria predicting low risk who
      have been treated with primary PCI or streptokinase. RESULTS: Forty-eight
      patients received streptokinase, and 49 had undergone primary PCI. Both during
      the in-hospital period and follow-up, the groups did not differ in the end points
      of death, reinfarction, or stroke (in-hospital: 2.1% versus 4.1%, P=.57; follow
      up: 8.9% versus 8.9%, P=1.000). Length of hospital stay was longer in the
      streptokinase group (6.5+/-2.5 versus 9.1+/-3.7 days, P=.001). Rate of repeat
      revascularization was reduced in the PCI group at 10 months (28.9% versus 55.6%,
      P=.002). CONCLUSIONS: When streptokinase and primary PCI are compared in isolated
      inferior acute myocardial infarction patients with a low-risk profile, there are
      no differences for in-hospital and long-term rates of death, reinfarction, or
      stroke. Primary angioplasty reduces the length of initial hospital stay, and
      reduces repeat admissions by decreasing the need for subsequent revascularization
      procedures. Large-scale studies are needed to reach a final conclusion.

PMID- 20802414
TI  - The application of biofeedback exercises in patients following arthroplasty of
      the knee with the use of total endoprosthesis.
AB  - BACKGROUND: Various methods and means are available for patients in
      rehabilitation after arthroplasty of the knee with total endoprosthesis,
      including the use of devices with biofeedback, thanks to which the patient learns
      conscious control of the given activity in a way adequate to the information
      received. Therapy with biofeedback is especially effective for individuals for
      whom pathological afferentation occurs, as a result of the ensuing pathological
      process affecting the limb. MATERIAL/METHODS: 18 patients following arthroplasty
      of the knee with total endoprosthesis due to degenerative changes were qualified
      for participation. The patients were divided into two groups depending on the
      time that had elapsed after surgery before rehabilitation was commenced. The
      tests were conducted twice, once before and once after the cycle of physiotherapy
      procedures. RESULTS: The measurement of the scope of active movements conducted
      in the first examination showed small differences between the two groups. Times
      were also analysed: the total time of exercise, time in the marked field, and
      time outside of it. In group 1 all the average values for these parameters were
      greater than in group 2. CONCLUSIONS: Commencement of the rehabilitation program
      within a few weeks after arthroplastry of the knee with total endoprosthesis
      brought better results than in the case of patients who entered rehabilitation 3
      months after surgery.

PMID- 20802415
TI  - The sequence polymorphism of MnSOD gene in subjects with respiratory
      insufficiency in COPD.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with the
      development of respiratory failure, which, in turn, exposes the tissues to
      oxidative stress, which is both a cause and a result of respiratory
      insufficiency. The first-line defense against oxidative stress is provided by the
      mitochondrial enzyme manganese superoxide dismutase (MnSOD), which is a
      superoxide anion scavenger. It is unknown whether genetic variability of the
      enzymes protecting against reactive oxygen species (ROS) can influence the
      development of respiratory failure in COPD patients. The aim of the study was to
      determine the correlation between polymorphism of MnSOD signal peptide and the
      occurrence of respiratory failure in the course of COPD. MATERIAL/METHODS: The
      study group consisted of 162 COPD patients (113 men and 49 women). The control
      group consisted of 63 subjects. Respiratory failure was diagnosed in 42 COPD
      patients. In all the examined subjects, the polymorphism resulting in alanine at
      residue 9 being replaced by valine and the expression of MnSOD in blood cells
      were determined. RESULTS: The Val/Val phenotype was demonstrated to occur in COPD
      patients more frequently than in the control group, as well as being associated
      with a lower expression level of MnSOD mRNA. Respiratory failure in the course of
      COPD also correlates with lower expression of MnSOD mRNA. CONCLUSIONS: The
      presence of valine at position 9 of the MnSOD signal peptide encoded by exon 2 is
      a risk factor for the occurrence of respiratory failure in the course of COPD in
      the Polish population.

PMID- 20802416
TI  - Immunization against influenza during the 2005/2006 epidemic season and the
      humoral response in children with diagnosed inflammatory bowel disease (IBD).
AB  - BACKGROUND: Patients with inflammatory bowel disease (IBD) who are treated long
      term with immunosuppressive drugs can experience a decrease in their overall
      resistance to infections, including influenza. The purpose of this study was to
      evaluate the humoral response in children with IBD after being vaccinated against
      influenza. MATERIAL/METHODS: Children with IBD were vaccinated with split
      inactivated vaccine. They were divided into 2 groups: children treated with anti
      inflammatory medications and children treated with 5-acetylsalicylic acid along
      with immunomodulatory therapy. Antihemagglutinin (anti-HA) and antineuraminidase
      (anti-NA) antibodies were assessed before vaccination and 1 and 6 months after
      vaccination. RESULTS: Anti-HA and anti-NA antibodies 1 and 6 months after
      vaccination were higher than before vaccination. In the patients treated with
      anti-inflammatory medications, the protection rate (PR) attained the highest
      level for antigens A/H1N1 and B 6 months after vaccination. However, for A/H3N2
      the result was 88.9% at 1 and 6 months after vaccination. In the patients who
      received immunomodulatory medications, the highest PR was noted 6 months after
      vaccination (47.6-90.5%). The response rate (RR) in patients who were treated
      with the anti-inflammatory medications alone remained the same 1 and 6 months
      after vaccination. In patients who received the immunomodulatory regimen, the
      highest RR was recorded 6 months after vaccination (47.6-76.2%). CONCLUSIONS:
      Response to vaccination was satisfactory, although not for all vaccine antigens,
      especially in patients treated with immunomodulatory medications. The higher
      levels of RP and RR 6 months after vaccination compared with 1 month after
      vaccination lends support to the argument that IBD patients should be vaccinated
      as soon as vaccine is available in a season.

PMID- 20802417
TI  - Kidney function assessed by eGFR, cystatin C and NGAL (neutrophil gelatinase
      associated lipocalin) in relation to age in heart allograft recipients.
AB  - BACKGROUND: Because creatinine is an unreliable variable describing kidney
      function, the search for a new and sensitive marker of kidney function is
      underway. Neutrophil gelatinase-associated lipocalin (NGAL) has been recently
      proven useful in the quantitation of chronic kidney disease (CKD). The aim of the
      study was to assess the prevalence of chronic kidney disease using estimated
      glomerular filtration rate (eGFR) and creatinine clearance according to different
      formulas and measurements of cystatin C and serum NGAL. MATERIAL/METHODS: One
      hundred sixty-nine prevalent heart transplant recipients in relation to age
      (younger and older than 65 years of age) were studied. Serum NGAL, cystatin C,
      creatinine, and eGFR were evaluated in all patients. RESULTS: Elderly heart
      recipients had significantly higher cystatin C and serum NGAL and lower eGFR than
      their younger counterparts, despite not having a statistically different serum
      creatinine. In the group of 27 elderly recipients, according to the Cockcroft
      Gault formula, 22 patients had stage 3 CKD and 4 had stage 4 CKD; according to
      the Modification of Diet in Renal Disease (MDRD) Study formula, 5 had stage 2
      CKD, 15 had stage 3 CKD, and 7 had stage 4 CKD; according to the Chronic Kidney
      Disease Epidemiology Collaboration (CKD-EPI) formula, 5 had stage 2 CKD, 15 had
      stage 3 CKD, and 7 had stage 4 CKD; and according to the calculation of 24-hour
      creatinine clearance, 5 had stage 2 CKD, 16 had stage 3 CKD, and 6 had stage 4
      CKD. CONCLUSIONS: The prevalence of CKD in the elderly population was as high as
      81% (MDRD, CKD-EPI, creatinine clearance) to 100% (Cockcroft-Gault formula),
      whereas in the younger population of heart transplant recipients the prevalence
      of CKD ranged from 56.3% to 77.5%. Serum NGAL could be a sensitive marker of
      kidney function, particularly in elderly patients.

PMID- 20802418
TI  - Determination of homovanillic acid and vanillylmandelic acid in urine of autistic
      children by gas chromatography/mass spectrometry.
AB  - BACKGROUND: Studies suggest dopamine nervous systems are involved in the
      pathogenesis of autistic disorder. Quantification of urinary homovanillic acid
      (HVA) and vanillylmandelic acid (VMA) can be a very important tool in the study
      of disorders of dopamine metabolism in autistic children. MATERIAL/METHODS: The
      urine specimens were collected from 20 autistic children and 36 neurologically
      normal children. Urinary HVA and VMA were simultaneously analyzed by gas
      chromatography-mass spectrometry. The method involves extraction of HVA and VMA
      from urinary samples and derivatization to N,O
      bis(trimethylsilyl)trifluoroacetamide derivatives. RESULTS: The detection limits
      are 0.15 microg/mL and 0.23 microg/mL for VMA and HVA, respectively. The levels
      of HVA and VMA were higher in the urine of autistic children (28.8+/-15.5
      micromol/mmol creatinine and 22.2+/-13.0 micromol/mmol creatinine, respectively)
      compared with those of the generally healthy children (4.6+/-0.7 micromol/mmol
      creatinine for HVA and 3.8+/-0.6 micromol/mmol creatinine for VMA). CONCLUSIONS:
      We proposed a simple, rapid method for a routine analysis of human urine to
      detect HVA and VMA related to an abnormal functional imbalance of the dopamine
      system, and showed our experience of application of this method to patients with
      a diagnosis of autism spectrum disorders. These results suggest significant
      differences in the levels of HVA and VMA between autistic and healthy children.

PMID- 20802419
TI  - Successful endoscopic clipping for bleeding from colonic angiodysplasia in a case
      of Heyde syndrome.
AB  - BACKGROUND: Aortic valve sclerosis, calcification, and stenosis are common in the
      elderly. Increased life expectancy has resulted in a growing population of
      elderly people, with a corresponding increase in the number of patients with
      these degenerative aortic valve diseases. CASE REPORT: We report a case of severe
      aortic stenosis in an 82-year-old woman with bleeding due to colonic
      angiodysplasia. The patient presented with anemia unexpectedly before her aortic
      valve replacement. Colon fiberscopy revealed that colonic angiodysplasia was
      responsible for the bleeding. The lesion was treated with endoscopic clipping
      before the successful aortic valve replacement. Additionally, her immunoblot
      analysis detected a decrease of large molecular weight multimers of von
      Willebrand factor. CONCLUSIONS: The relationship between aortic valve stenosis,
      acquired von Willebrand disease and gastrointestinal bleeding in elderly patients
      is known as Heyde syndrome. Clinicians should be aware of the possibilities of
      acquired von Willebrand disease and gastrointestinal bleeding from angiodysplasia
      in patients with aortic valve stenosis.

PMID- 20802420
TI  - Intra-abdominal hypertension in fulminant Clostridium difficile infection--an
      under-recognized treatable complication.
AB  - BACKGROUND: Clostridium difficile is the most common cause of nosocomial
      infectious diarrhea in adults, with recent reports of increased severity and case
      fatality. Intra-abdominal hypertension (IAH) and abdominal compartment syndrome
      (ACS) are increasingly recognized and treatable complications of severe illness
      in medical patients, and are independent predictors of mortality. Patients with
      severe Clostridium difficile infection (CDI) are at increased risk for IAH and
      ACS. However, ACS has been only rarely described in this population. CASE REPORT:
      We report a case of a 61 year-old morbidly obese, chronically ill, ventilator
      dependent patient, who developed fulminant CDI, including progressive colonic
      distension, acute renal failure and intra-abdominal fluid sequestration. Her
      clinical course worsened abruptly, with new shock, worsening hypoxic respiratory
      failure, increased peak airway pressures and reduced tidal volumes. Intra
      abdominal pressure was 30 mm Hg. The patient was not considered a surgical
      candidate, was refractory to escalating non-surgical support, and died following
      withdrawal of life support. CONCLUSIONS: Although patients with fulminant CDI
      share many risk factors for IAH and ACS, these conditions were rarely reported in
      this population and are likely under recognized, as was the case with the present
      patient. Increased vigilance for IAH is needed in this at-risk population.

PMID- 20802421
TI  - Vasoplegic shock during liver transplantation: is the preoperative cGMP plasma
      level a potential predictor of hemodynamic instability?
AB  - BACKGROUND: Refractory hypotension is a frequent event during reperfusion of a
      liver graft. Measures that help maintain hemodynamic stability include correction
      of electrolytes and acid-base abnormalities as well as administration of fluid
      and/or catecholamines. Vasoplegic syndrome represents the most severe form of
      hemodynamic instability. Management of this condition is very difficult due
      primarily to the inadequate response to even very high doses of catecholamines.
      CASE REPORT: A 60-year-old patient presented for liver transplantation due to end
      stage liver disease. After an initially uneventful hepatic phase, the patient
      developed excessive tachycardia and refractory hypotension during cross-clamping
      of the vena cava. The situation rapidly deteriorated despite administration of
      fluid and extremely high doses of norepinephrine and vasopressin. A
      transesophageal echocardiogram (TEE) performed at that time failed to demonstrate
      any cardiac dysfunction or signs of pulmonary emboli. Subsequent blood cultures
      and imaging studies did not confirm any signs of sepsis. Further investigation
      revealed an increased preoperative level of cyclic guanosine monophosphate
      (cGMP). cGMP is the second messenger for nitric oxide, and is responsible for
      relaxation of vascular smooth muscle with subsequent vasodilatation. This finding
      suggests a release of nitric oxide in the systemic circulation which could have
      been a potential cause for vasoplegic shock. CONCLUSIONS: Release of nitric oxide
      in the systemic circulation can be a potential cause of vasoplegic syndrome.
      Future investigation will demonstrate whether a patient's preoperative cGMP
      plasma level can be a potential predictor of intraoperative hemodynamic
      instability.

PMID- 20802423
TI  - Is lipoxins A4 a better alternative to anti-TNF-alpha antibody to prevent and
      treat diabetic macular edema and retinopathy?

PMID- 20802422
TI  - Silk fibroin added to calcium phosphate cement to prevent severe cardiovascular
      complications.
AB  - As a bone cement in vertebroplasty and kyphoplasty, calcium phosphate cement
      (CPC) has several advantages over polymethylmethacrylate (PMMA) including
      biomcompatibility, biodegradability and osteoconductivity. However, its decay
      properties raise the risk of pulmonary embolism and consequent cardiovascular
      complications. Animal experiments have demonstrated that the disintegration of
      CPC forming more emboli, especially microemboli, causes more severe
      cardiovascular deterioration than PMMA. Current efforts focus on the
      incorporation of organic proteins or polymers into CPC to improve its stability
      in fluids, by enhancing the hydroxyapatite (HA) formation and reducing the fluid
      penetration. Silk fibroin (SF) can regular the mineralization process and bond
      with HA to form fibroin-HA nanocomposites with increased gelation properties. SF
      also has excellent biomechanical, biocompatible and biodegradable properties, and
      is convenient and inexpensive to produce. We hypothesize that silk fibroin can be
      used as an additive to improve the cohesion of CPC and decrease its risk of
      cardiovascular complications in its application in veterbroplasty/kyphoplasty.

PMID- 20802424
TI  - Antimicrobial activity of ozonated water.
AB  - BACKGROUND: The purpose of this study was to analyze basic bactericidal and
      fungicidal activity of ozonated water according to EN 1040 "Chemical
      disinfectants and antiseptics--Quantitative suspension test for the evaluation of
      basic bactericidal activity of chemical disinfectants and antiseptics" and EN
      1275 "Chemical disinfectants and antiseptics--Quantitative suspension test for
      the evaluation of basic fungicidal or basic yeasticidal activity of chemical
      disinfectants and antiseptics" with additional clinical multidrug-resistant
      bacterial strains and evaluate whether the ozonated water acts as a rapid and
      efficient antimicrobial agent and as such could be applied during intraoperative
      ozone treatment for tissue protection against infection with pathogenic bacteria.
      MATERIAL/METHODS: A prototype device for intraoperative ozone therapy was used.
      Besides standard bacterial and fungal strains, 60 clinical bacterial isolates
      were analyzed. RESULTS: The ozone concentration in ozonated water was sufficient
      to kill almost all cells of the bacterial and yeast strains tested after 30
      seconds. Effective action against Aspergillus brasiliensis spores required a
      longer time than those required in the case of bacterial cells or vegetative
      cells of yeast. CONCLUSIONS: The prototype device used in our study produced high
      ozone concentrations in freshly prepared ozonated water. This liquid complied
      with the requirements of the EN Standards: basic bactericidal and basic
      yeasticidal activities.

PMID- 20802425
TI  - Personality traits assessed by the NEO Five-Factor Inventory (NEO-FFI) as part of
      the perinatal depression screening program.
AB  - BACKGROUND: As pre- and postnatal depression is a multifactorial disorder, the
      screening programmes which are currently in use in obstetric clinics remain
      problematic due to their inadequate standardization and limited efficacy. The
      evaluation of core risk factors for perinatal depression in the screening
      process, in addition to routine questionnaire-based tools such as the Edinburgh
      Postnatal Depression Scale (EPDS), might improve the diagnosis and early
      treatment of women affected by depression. This study was undertaken to analyze
      the relationship between personality traits and the risk of perinatal depression
      in pregnant and postpartum women. MATERIAL/METHODS: For the study, 229 patients
      (pregnant and postpartum women) admitted to an obstetric hospital in Poland were
      recruited. Two self-report questionnaires were used: the Edinburgh Postnatal
      Depression Scale (EPDS) as a screening tool for depressive symptoms and the NEO
      Five-Factor Inventory (NEO-FFI) for the evaluation of five personality traits in
      the studied patients. RESULTS: Neuroticism significantly increased the risk of
      perinatal depressive symptoms in both pregnant and postpartum women (OR=1.23 and
      OR=1.11, respectively). Personality traits related to a lower risk of perinatal
      depression in the group of pregnant women included extraversion, openness to
      experience, high degree of agreeableness and conscientiousness (OR=0.90, OR=0.92,
      OR=0.90 and OR=0.91, respectively). However, among at-risk postpartum women no
      additional factors, except neuroticism, affected the prevalence of depressive
      symptoms. CONCLUSIONS: Personality trait like neuroticism as measured by the NEO
      FFI is associated with a greater risk of perinatal depression. The NEO-FFI is a
      useful tool, potentially adding significant value to the program of perinatal
      depression screening.

PMID- 20802426
TI  - The efficacy of treatment for systemic sclerosis interstitial lung disease:
      results from a meta-analysis.
AB  - BACKGROUND: This meta-analysis examined all randomized controlled trials (RCTs)
      comparing pharmacotherapy for systemic sclerosis (SSc)-interstitial lung disease
      (ILD) with placebo or alternative drugs on pulmonary function tests (PFTs),
      quality of life, dyspnea, skin thickness, and adverse events. MATERIAL/METHODS:
      Forty studies were identified, and from these 2 RCTs examining cyclophosphamide
      and 1 examining bosentan met inclusion criteria (studies had to be randomized,
      have at least 20 SSc-ILD patients, and have PFTs as primary outcomes). RESULTS:
      Differences between groups for change of PFT scores between baseline and 12
      months were not significant when the 3 trials were combined. The treatment effect
      of cyclophosphamide versus placebo on forced vital capacity revealed a mean
      difference of 3.30% (95% confidence interval, 0.06-6.54). Diffusing capacity and
      total lung capacity did not change. CONCLUSIONS: This conservative yet
      significant effect of cyclophosphamide demonstrates the need for further
      investigation of its effectiveness on patient-important outcomes such as dyspnea
      and quality of life, which could not be evaluated by this meta-analysis. It may
      be that studies in SSc-ILD need outcomes that are more sensitive to change.

PMID- 20802427
TI  - Associations between HLA molecules and ophthalmologic diseases.
AB  - The aim of this review was to analyze associations between HLA (human leukocyte
      antigens) alleles described thus far and an array of ophthalmologic disorders.
      Highly polymorphic HLA molecules play a crucial role in immunological response to
      various pathogens. Due to environmental pressures exerted mostly by infectious
      factors in the past, population frequencies of particular alleles differ greatly
      and modulate immunological response in various diseases. Associations between HLA
      alleles and over 500 pathologies, mainly autoimmune, infective and inflammatory
      diseases, have been previously described. In the course of certain HLA-related
      diseases described so far, eye manifestations are present. In this paper we
      review the structure, function and linkage between HLA antigens, ophthalmologic
      diseases and systemic disorders with eye involvement.

PMID- 20802428
TI  - Retrospective analysis of paediatric injuries associated with water in Czech
      Republic in the context of the European at worldwide situation.
AB  - BACKGROUND: Injuries encountered in association with the aquatic environment
      negatively affect morbidity and mortality rates in children. It is the second (in
      Bohemia the third) most frequent cause of injuries in children under 19 years of
      age. The targets of the study are as follows: to analyse the problems of
      children's injuries associated with water in the Czech Republic by the mechanism
      of their origination; to compare the analysis of results with the situation
      abroad; to evaluate risk factors associated with the aquatic environment.
      MATERIAL/METHODS: The group includes 802 children aged 0-19 years who experienced
      accidents associated with the aquatic environment between 2002 and 2006; 14%
      drowned, 48% nearly drowned, 37% suffered injuries. The basic data for the study
      presented here was accumulated from multiple sources (statistical data, secondary
      analyses of documents, reports of the integrated emergency service, water rescue
      service, etc.). RESULTS: The results were statistically processed by the squared
      chi method. A statistically significant relationship was established between
      injuries originating in pools and the preschool age. (35.6%) No statistical
      significance was demonstrated with other variables. CONCLUSIONS: The authors
      discuss the possibilities of providing safety for children at pools and in the
      vicinity of water reservoirs. They emphasise the necessity of permanent,
      concentrated surveillance on the part of parents and the building of protective
      devices restricting free access to the pool.

PMID- 20802429
TI  - [Ultraconservative treatment in stage I and II breast carcinoma. Results of a
      long-term follow-up on 500 operated breasts].
AB  - AIM: Several randomized trials on conservative surgery compared with mastectomy
      in early-stage breast cancer have validated this technique in terms of local and
      distant relapse and survival of patients. Standard conservative approach includes
      surgical removal of the cancer with adequate cancer-free margins, axillary
      dissection, postoperative breast irradiation and adjuvant treatments when
      required. METHODS: From 1987 to 2003, 500 early stage breast carcinoma were
      treated on 494 patients with conservative surgery and postoperative radiotherapy.
      Surgery consisted in a wide tumorectomy, with intraoperative control of R0
      margins. The total postoperative radiation dosage was 50 Gy on the whole breast,
      associated with a boost of 10 Gy on tumor bed (20 Gy in T2 neoplasms). Before
      1997 node-positive patients were treated with axillary irradiation with 50 Gy.
      Postoperative chemotherapy and/or hormonal therapy were administered to patients
      according with node-involvement, age and menopausal status. AJCC-stage was T1N0
      in 44%, T2N0 in 15%, T1N1 in 19% and T2N1 in 22% of the patients. RESULTS: In a
      postoperative setting, we observed 9% of axillary seromas or hematomas and 7% of
      oedema of the arm. At a median follow-up of 150 months (range 48-248 months),
      actuarial local recurrence rates were 7% at 5 years and 14% at 10 years. The
      actuarial rates of distant metastases were 18% at 5 years and 33% at 10 years.
      Ten-year overall and disease-free survival rates were 81% and 60%, respectively.
      Cosmetic results were good/excellent in 80%, satisfactory in 10% and poor in 10%
      of patients. CONCLUSION: Recurrence and survival rates in breast-conserving
      surgery are consistent with indexed literature on conservative treatment of early
      breast cancer. Women eligible for conservative treatment should be offered the
      choice of either wide tumorectomy or quadrantectomy with axillary lymph nodes
      removal and postoperative radiotherapy, or modified radical mastectomy.

PMID- 20802430
TI  - Role of computer technology in neurosurgery.
AB  - In the clinical office, during surgical planning, or in the operating room,
      neurosurgeons have been surrounded by the digital world either recreating old
      tools or introducing new ones. Technological refinements, chiefly based on the
      use of computer systems, have altered the modus operandi for neurosurgery. In the
      emergency room or in the office, patient data are entered, digitally dictated, or
      gathered from electronic medical records. Images from every modality can be
      examined on a Picture Archiving and Communication System (PACS) or can be seen
      remotely on cell phones. Surgical planning is based on high-resolution
      reconstructions, and microsurgical or radiosurgical approaches can be assessed
      precisely using stereotaxy. Tumor resection, abscess or hematoma evacuation, or
      the management of vascular lesions can be assisted intraoperatively by new
      imaging resources integrated into the surgical microscope. Mathematical models
      can dictate how a lesion may recur as well as how often a particular patient
      should be followed. Finally, virtual reality is being developed as a training
      tool for residents and surgeons by preoperatively simulating complex surgical
      scenarios. Altogether, computerization at each level of patient care has been
      affected by digital technology to help enhance the safety of procedures and
      thereby improve outcomes of patients undergoing neurosurgical procedures.

PMID- 20802431
TI  - The present role of vertebroplasty and kyphoplasty in the treatment of fresh
      vertebral compression fractures.
AB  - Vertebroplasty (VP) and kyphoplasty (KP) are minimally invasive vertebral
      augmentation procedures for the treatment of fresh vertebral compression
      fractures (VCFs) associated with osteoporosis, trauma, malignant conditions,
      hemangiomas, and osteonecrosis. During these procedures, bone cement (e.g.,
      polymethylmethacrylate) is percutaneously injected into the vertebral body.
      Systematic reviews of both procedures have shown significantly improved back pain
      and quality of life compared to conservative therapy. Direct comparison between
      VP and KP is not possible because of the lack of prospective randomized data
      comparing the two procedures. Both appear to improve patient functional status in
      most studies, although it is difficult to pool the available data because of
      differing measurement scales. With increasing popularity of both techniques,
      particularly over the past ten years, a rising number of publications have
      detailed potential complications secondary to cement extravasation, from
      compression of neural elements to venous embolism. Overall complication rates for
      both procedures are low. Systematic reviews have found significantly higher rates
      of cement leakage after VP (40%) versus KP (8%), with 3% of VP leaks being
      symptomatic. The evidence for increased risk of adjacent level fracture after
      these procedures compared to conservative treatment is inconclusive. When
      performed by a well-trained practitioner in appropriately selected patients,
      vertebroplasty and kyphoplasty are both safe and effective treatments for fresh
      vertebral compression fractures. Results from ongoing randomized controlled
      trials will provide further detailed information about both procedures in the
      future.

PMID- 20802432
TI  - Computer aided minimally invasive cardiac procedures.
AB  - Minimally invasive cardiac procedures have been investigated to reduce the risks
      associated with open heart surgery. With the assistance of improvements in
      engineering technologies such as medical imaging, surgical navigation, and
      robotic devices, more cardiac surgeries can be performed in a minimally invasive
      fashion. We have surveyed these state-of-the-art engineering technologies and the
      minimally invasive cardiac procedures that are benefited from these technologies.

PMID- 20802433
TI  - Intraoperative augmented reality for laparoscopic colorectal surgery by
      intraoperative near-infrared fluorescence imaging and optical coherence
      tomography.
AB  - Advances in imaging quality and capability have been the major driver of the
      laparoscopic revolution that has dramatically impacted upon operative strategies
      and surgical patient care in recent years. Increasingly now the technological
      capacity is becoming available to supraselect or extend the useful clinical range
      of the electromagnetic spectrum beyond visible or white light. This has markedly
      broadened the intraprocedural optical information available at intraluminal
      endoscopy and there is likely to be considerable similar benefit for laparoscopy.
      Rather than narrow band or ultraviolet imaging however, it is the near infrared
      (NIR) spectrum that seems of most potential to exploit during intra-abdominal
      endoscopy in particular as this energy range is capable of penetrating relatively
      deeply into tissues such as the mesentery and bowel wall without inducing thermal
      damage due to heat dissipation or indeed the intracellular effects associated
      with higher energy, shorter wavelength energies. By incorporating the NIR
      spectrum alongside more conventional laparoscopic imaging, a greater appreciation
      of tissue architecture, character and quality is possible in particular with
      respect to lymphatic and vascular channel anatomy and flow dynamics and also real
      time optical histology (by NIR optical coherence tomography). Such a facility may
      significantly aid critical intraoperative decision making during colorectal
      operations by informing the surgeon regarding the most biologically relevant
      lymphatic basin and lymph nodes for any target area of interest (especially
      important if considering tailored operative extent for colorectal neoplasia), the
      sufficiency and quality of arterial supply (and hence inform re the perfusion of
      stapled intestinal ends prior to reanastomosis) and perhaps even in situ
      pathological assessment. This article provides a state of art overview of the
      fascinating potential of this emergent technological capability.

PMID- 20802434
TI  - Advances in image guided conventional and minimal invasive liver surgery.
AB  - Technological developments, advances in perioperative medicine and ongoing
      scientific research have led to reduced rates of mortality and morbidity in
      patients undergoing major liver surgery. Under these conditions, the frontier of
      resectability is constantly in movement towards more complex cases with extended
      tumor spread and potentially minimized remnant liver volume. A promising
      technique to support oncological correct and safe liver surgery is the
      introduction of preoperative computer based planning models and intraoperative
      navigation systems. Whereas three-dimensional (3D) liver models are commercially
      available and have been clinically implemented, the use of navigation systems is
      currently under evaluation by different groups using a variety of techniques.
      This manuscript is meant to give the reader an overview on current developments,
      difficulties and future aspects of image guided liver surgery.

PMID- 20802435
TI  - [Retroperitoneal dedifferentiated liposarcoma (DDLS) with hyperglycemic activity:
      case report and literature review].
AB  - The authors describe a Retroperitoneal De Differentiated LipoSarcomas (DDLs),
      that for its clinical behavior shows peculiar characteristics and original
      aspects: typical is the recurrence due to local invasiveness, but absolutely
      original seems to be the surviving time, maybe correlated to its histological
      evolution (dedifferentiation from leiomyosarcoma to liposarcoma) and an
      interesting correlation from the tumor recurrence and the glycemic curve first
      and after the surgical treatments. A 66-year-old woman, presenting typically with
      very big abdominal masses, treated three times in almost three years, every time
      with aggressive surgical treatments. Histological response was leiomyo-sarcoma in
      the first two operations and liposarcoma in the last treatment and in every
      preoperative phase the patient, normally prediabetic, started to have problem of
      glycemia balancing, needing an insulin support until the postoperative phases
      when its glycemia was coming back in normal value without insulin needs, of
      course until a new tumor recurrence. This last aspect, not depending on pancreas
      involvement or hormonal activity (immune-histo-chemistry was never conforming a
      neuro-endocrine activity), seems probably due directly to a mass and metabolic
      effect of the tumor. Beginning from the description of this case and its
      interesting biology and reviewing most of the literature on the argument, authors
      hope to give our support to still debated and partially unknown aspects of these
      kinds of tumors.

PMID- 20802436
TI  - Malignant phaeochromocytoma with cavoatrial extension: transcaval removal of
      tumor without cardiopulmonary bypass A case report.
AB  - Adrenal carcinoma is a rare tumor and with metastasis usually in lungs, lymph
      nodes, liver, and bones. However, intracaval invasion extending into the right
      atrium is very rare. The surgical approach to adrenal tumor extending into the
      vena cava is challenging. The optimal surgical approach of tumor with inferior
      vena cava extension depends on the level of vena cava involvement. This article
      reports a case of malignant pheochromocytoma extending into the cavoatrial
      junction in a young man.

PMID- 20802437
TI  - Intravenous leiomyomatosis: report of two cases and strategy for surgical
      resection.
AB  - Intravenous leiomyomatosis is a rare smooth muscle tumour that arises from the
      myometrium and grows into the extrauterine venous system. It typically can extend
      into the vena cava inferior and even the cardiac chambers. This can lead to life
      threatening obstruction of cardiac valves. The only effective treatment is
      surgical resection. However, no clear guidelines with respect to surgical
      approach and further strategy are available in the literature. Especially the
      indications for a simultaneous thoracic approach and for either one-stage or two
      stage approach are unclear. On the basis of two cases of intravenous
      leiomyomatosis with different levels of intracaval extension of the tumour, this
      article discusses a useful strategy for planning surgical resection, taking into
      account tumour characteristics and different levels of intracaval extension.

PMID- 20802438
TI  - Ultra structural evidence of axonal regeneration following intracranial
      transection of optic nerve.
AB  - OBJECTIVE: The present work was aimed at studying the ultra structural changes of
      the proximal (retinal) stump of the intracranially transected optic nerve of the
      rat for any possible regenerative ability. METHODS: Specimens were collected one
      (1 wpo) and four weeks(4 wpo) after the transection and the cross sections of the
      stumps were studied by electron microscopy by dividing them into three zones, (1)
      the central zone, (2) the intermediate zone, and (3) the peripheral zone.
      RESULTS: The present results showed evident morphological changes in these zones
      both in the 1 wpo and 4 wpo groups. The signs of degeneration were more marked in
      the central zone than in the peripheral zone and they were more prominent in the
      1 wpo group than in the 4 wpo group. The most prominent sign of the degeneration
      was loss or lack of the healthy myelinated axons. The main evidence of the
      regenerative ability was the reappearance of the apparently healthy myelinated
      axonal profiles, with a parallel decrease of the non myelinated ones. This
      regenerative feature was more prominent peripherally and might be an indication
      that ischemia was the cause of optic nerve degeneration. CONCLUSIONS: The present
      work revealed a clear morphological evidence of the regenerative capability of
      the intracranially transected optic nerve though it is considered as a part of
      the CNS.

PMID- 20802439
TI  - Time-dependent axonal impairment in experimental model of brain oedema.
AB  - OBJECTIVES: Clinically very serious condition of ischaemia and brain injury which
      are often associated with brain oedema is frequently accompanied by the
      impairment of the structural integrity of axons. We wondered whether the brain
      oedema (without ischemia brain injury) can induce structural axonal impairment.
      METHODS: Brain oedema was induced by osmotic blood-brain barrier opening with 20%
      mannitol applied selectively into the internal carotid. Axonal changes were
      recognized as signs of myelin disintegration (oedematous vesicles, varicosity,
      myelin fragmentation) at histological sections stained with Black Gold in
      hippocampal areas CA1 and CA3 and in the dentate gyrus and cerebral cortex at
      time intervals of one hour, one day, three days and one week after the oedema
      induction. RESULTS: Impairment of the structural integrity was identified in
      myelin sheets in all areas studied in all experimental groups. Whereas in the
      control group axon were of the uniform diameter, in the experimental groups
      various forms of myelin disintegration were observed. The progression of myelin
      damage depended on the time elapsed after the oedema induction. CONCLUSION:
      Opening the blood-brain barrier with an osmotic insult induces brain oedema which
      represents a factor triggering axonal impairment accompanied with myelin changes.
      The development of axonal changes initiated by brain oedema only (without
      ischemia brain injury) is a novel observation.

PMID- 20802440
TI  - The endocrine and metabolic evaluation of benign symmetrical lipomatosis: a case
      report and literature review.
AB  - OBJECTIVE: Benign symmetrical lipomatosis (BSL) is a rare disease characterized
      by the presence of multiple, symmetric and nonencapsulated fat masses. Alcoholism
      is observed in nearly 90% patients. However the etiology of this disease is still
      unclarified. BSL is very rare in Chinese people. Herein we described the
      endocrine and metabolic status of a patient with typical BSL. We also discussed
      the clinical manifestation, etiology, diagnosis and treatment for BSL. RESULTS:
      Hyperuricemia and abnormal liver enzyme levels were observed in this case.
      However insulin sensitivity and function of the thyroid, adrenal glands and
      pituitary were all normal. The insulin sensitivity was assessed by the
      hyperinsulinemic euglycemic clam. CONCLUSIONS: Although an association had been
      found between BSL and some endocrinological or metabolic disorders including
      abnormal glucose tolerance, excessive secretion of insulin, hyperuricemia, and so
      on, they were not specific for BSL. It is necessary to develop into the
      pathogenesis of BSL further.

PMID- 20802441
TI  - The effects of parametric speaker sound on salivary hormones and a subjective
      evaluation.
AB  - OBJECTIVE: Recently, a parametric speaker system has been developed. However, the
      safety of the parametric speaker for the human body has not yet been
      demonstrated. Therefore, we studied the effects of parametric speaker sound on
      salivary hormones and carried out a subjective evaluation. METHODS: Nine male
      subjects participated in this study. They completed three consecutive sessions: a
      20-min quiet period as a baseline, a 45-min mental task period with either a
      general or parametric speaker, and a 20-min recovery period. The subjects were
      evaluated by the salivary cortisol and chromogranin A (CgA) concentrations. In
      addition, they took the Kwansei-Gakuin sleepiness scale (KSS) test before and
      after the task and also a sound quality evaluation test after it. Two
      experiments, one with a general speaker (general condition) and the other with a
      parametric speaker (parametric condition), were conducted at the same time of day
      on separate days. To examine the effects of the parametric speaker, a two-way
      repeated measures ANOVA (speaker factor and time factor) was conducted. RESULTS:
      The results showed that the cortisol concentration was significantly lower during
      the parametric condition than during the general condition. Furthermore, the
      sound quality evaluation found a "warm" sensation during the parametric condition
      to be lower than that during the general condition. A "noisy" sensation during
      the parametric condition tended to be higher than during the general speaker.
      However, the CgA concentration and the KSS score were not significantly different
      for either the speaker factor or the time factor. CONCLUSION: The results
      suggested that the burden of the parametric speaker was smaller than that of
      general speaker, especially on the HPA-axis in the endocrine system.

PMID- 20802442
TI  - Testosterone and cortisol levels in university students reflect actual rather
      than estimated number of wrong answers on written exam.
AB  - OBJECTIVES: After dominance-related encounters, testosterone levels increase in
      winners and decrease in losers. In humans, many exceptions have been described.
      It is possible that the complicated patterns in humans result from the methods
      limitations--measurement of hormone concentrations in simulated competitive
      events or sport instead in real-life situations. METHODS: Here we studied changes
      in hormonal levels and self-estimated attractivity in real situations, namely in
      students after written exams. RESULTS: We observed that the testosterone and
      cortisol increased or decreased in relation to the number of wrong answers on the
      exam. The number of wrong answers was a better predictor of the hormonal changes
      (increase of both testosterone and cortisol in successful, decrease in
      unsuccessful students) than the self-estimated number of wrong answers or a
      subjectively opinionated impression from the exam. On the contrary, the
      concentration of hormones before the exam and self-estimated attractivity were
      better predictors of the subjective impression from the exam than the number of
      wrong answers. CONCLUSIONS: Our results suggest that the students'
      subconsciousness, which directly influences the concentration of hormones, is
      able to objectively estimate results of an exam better than their consciousness.

PMID- 20802443
TI  - Serum testosterone concentration in male autistic youngsters.
AB  - OBJECTIVE: Research on the biological pathophysiology of autism has found some
      evidence that alterations in androgenic hormones may play a role in the
      pathophysiology of that disorder. We studied morning concentrations of serum
      testosterone in a very homogenic group of postpubertal youngsters with autism and
      a group of normal controls. METHODS: This study examines the serum testosterone
      concentration on 9 consecutive time points between 08.00 AM and 12.00 AM in 18
      high- functioning male youngsters with autism (age 12-18) and 22 healthy
      volunteers participated in this study. All subjects passed the onset of puberty
      (Tanner-stage III-IV) and were of the Caucasian race. RESULTS: Repeated measures
      ANOVA revealed a significant time effect, with a decline in the testosterone
      concentration during the test and time X diagnosis interaction.The total
      testosterone concentration was significantly lower in the autism group compared
      to the group of normal controls. CONCLUSIONS: The significant decrease in serum
      testosterone concentration in male youngsters with autism suggest that the
      turnover of testosterone may take part in the pathophysiology of autism.
      Suggestions for further research are discussed.

PMID- 20802444
TI  - Potential pathomechanisms of ADHD based on neurometabolite changes.
AB  - Attention deficit hyperactivity disorder (ADHD) is a most common psychiatric
      disorder in the childhood. The exact pathomechanisms related to ADHD core
      symptoms--hyperactivity, impulsivity and inattention--are still unclear. The
      developmental dysfunction of cortical-striatal-thalamic-cortical network combined
      with the dysregulation of catecholamine neurotransmitters could be responsible
      for symptoms of the disorder. Magnetic resonance spectroscopy is a method which
      allows a partial view on molecular mechanisms of biochemical and metabolic
      processes in human brain by in vivo measurement. We address the hypothesis of a
      potential pathomechanisms associated with ADHD symptoms which is based on the
      studies concerning magnetic resonance spectroscopy method and ADHD.

PMID- 20802445
TI  - Placental first trimester's measurements in relation to maternal plasma
      adiponectin, leptin and insulin concentrations.
AB  - OBJECTIVE: The dysregulation of adiponectin and leptin is found in insulin
      resistance. There is evidence that both cytokines and insulin might contribute to
      the placental development and the fetal growth. The objective of this study was
      to evaluate the relationship of maternal plasma cytokine and insulin
      concentrations with the placental dimension in the first trimester of pregnancy.
      METHODS: 34 women with singleton pregnancy, between 11th and 14th weeks, were
      included to the study. Plasma levels of adiponectin, leptin, insulin and glucose
      were quantified with ultrasound measurements of the placenta. HOMA-IR were
      calculated to assess the insulin sensitivity. RESULTS: Mean concentrations of
      adiponectin, leptin and insulin were 18,39+/-13.99 ug/ml; 6.99+/-5.67 ng/ml and
      43.98+/-23.89 pmol/l respectively. The placenta thickness was positively
      associated with the maternal adiponectin plasma concentration (r=0.36; p=0.037).
      There were no associations between placental measurements and leptin, fasting
      insulin, fasting glucose and HOMA-IR. There was not significant correlation
      between placental measurements and the fetal Crown Rump Length (CRL).
      CONCLUSIONS: The results of this study imply that maternal adiponectin plasma
      concentration may have a role in placental growth.

PMID- 20802446
TI  - Parathyroid adenoma presenting as tetraparesia.
AB  - OBJECTIVE: Parathyroid adenomas (PA) are benign tumors. We report an unusual case
      of delayed diagnosis of a PA and concomitant Vitamin D deficiency presenting as
      tetraparesia. METHODS: A 30-year-woman was admitted to our clinic with an
      inability to walk. Our examination revealed tetraparesia and common, severe
      muscular atrophy. RESULTS: Laboratory investigations showed the following:
      creatinine phosphokinase (CK): 37 IU/L (15-130), calcium (Ca): 11.5 mg/dL (9-11),
      phosphorus (P): 1.5 mg/dL (2.5-5), parathyroid hormone (PTH): 736.1 pq/mL (15
      65), 25-hydroxyvitamin D (25-OHvit D): 4 ng/mL (11-43), and alkaline phosphatase
      (ALP): 1029.5 lU (64-300). Parathyroid scintigraphy revealed PA. A year after
      Vitamin D replacement, the patient's neurological status and laboratory findings
      improved. CONCLUSION: We suggest that the physicians always keep in mind the
      primary hyperparathyroidism (HPT) and concomitant Vitamin D deficiency in the
      differential diagnosis of hypercalcemia when facing atypical neurological
      symptoms such as tetraparesia.

PMID- 20802447
TI  - No association with the ETM2 locus in Czech patients with familial essential
      tremor.
AB  - OBJECTIVES: Essential tremor (ET) is one of the most common neurological movement
      disorders. In more than half of the cases, ET is inherited in an autosomal
      dominant manner, but no causative ET gene has been identified. However, several
      candidate loci have been reported, including the ETM2 locus that was originally
      found in a large American family of Czech descent. METHODS: To ascertain the
      association with ETM2, we performed a genetic analysis of three polymorphic loci,
      etm1231, etm1234, and etm1240, located within the ETM2 candidate region in 61
      Czech patients with a family history of ET and 68 healthy controls. RESULTS: The
      allele frequencies were not significantly different between the patients and the
      controls, and we did not observe any haplotype specifically associated with ET.
      CONCLUSIONS: This is the first report on the genetics of familial essential
      tremor in Czech patients. Our findings provide further evidence of genetic
      heterogeneity for ET.

PMID- 20802449
TI  - Maternal plasma adipokines and insulin concentrations in relation to fetal
      biometry in the gestational diabetes.
AB  - OBJECTIVE: Maternal insulin sensitivity have strong correlation with fetal
      growth. The dysregulation of adiponectin and leptin is found in insulin
      resistance. The aim of this study was to determine whether there is an
      association between ultrasound fetal biometry and the maternal plasma cytokines
      and insulin concentrations at the beginning of gestational diabetes treatment.
      METHODS: 121 women with gestational diabetes diagnosed between 26th and 30th
      weeks, were included to the study. Plasma levels of adiponectin, leptin, insulin
      and glucose were quantified with the measurements and percentiles of the
      biparietal diameter, head circumference and abdominal circumference , estimated
      fetal weight and the actual birthweight. RESULTS: Associations between both of
      the adipokines and fetal biometry measurements were not evident. There were also
      no differences in their serum concentrations between groups of women with and
      without accelerated fetal growth . Adiponectin negatively correlated with pre
      pregnancy BMI (r=-0.366, p=0.01). Leptin positively correlated with pre -
      pregnancy BMI (r=0.42, p=0.002), fasting insulin (r=0.51, p=0.0006) and HOMA-IR
      (r=0.43, p=0.005). No association was found between adiponectin, leptin, fasting
      insulin, HOMA-IR and neonatal birth weight or birth weight percentile.
      CONCLUSION: The results of this study imply that adiponectin, leptin and insulin
      maternal plasma concentrations in the third trimester do not have influence on
      fetal growth in gestational diabetes.

PMID- 20802448
TI  - N-acetylserotonin reduces lipopolysaccharide-induced lipid peroxidation in vitro
      more effectively than melatonin.
AB  - OBJECTIVE: Bacterial lipopolysaccharide (LPS) causes lipid peroxidation (LPO). We
      have found that LPS induces LPO in vitro, in tissue homogenates in a
      concentration-dependent manner, the concentration of 400 ug/ml demonstrating the
      most efficient lipid damaging effect . Both melatonin and its precursor, N
      acetylserotonin, must possess antioxidant activities, both in vivo or in vitro,
      however, following some claims, N-acetylserotonin is a more effective extra- and
      intracellular antioxidant than melatonin. The aim of our study was to compare the
      effects of melatonin and N-acetylserotonin on the LPS-induced LPO in vitro.
      METHODS: Malondialdehyde (MDA) plus 4-hydroxyalkenal (4-HDA) concentrations were
      measured as the indices of induced membrane peroxidative damage in brain, liver
      and kidney homogenates. Both melatonin and N-acetylserotonin were used at
      increasing concentrations, starting from 0.01-5 mM, together with LPS at one
      concentration level of 400 ug/ml. RESULTS: In all the examined tissues, LPS
      stimulated LPO, while both melatonin and N-acetylserotonin decreased LPS
      stimulated LPO. Furthermore, the capacity of N-acetylserotonin reducing LPO was
      higher than that of melatonin. CONCLUSIONS: The results of the reported study
      clearly indicate that N-acetylserotonin is a much stronger antioxidant in vitro
      than melatonin in terms of reducing oxidative damage to lipid membranes. However,
      it remains still unclear how the features relate to in vivo circumstances.

PMID- 20802450
TI  - Magnetic seizure therapy (MST)--a safer method for evoking seizure activity than
      current therapy with a confirmed antidepressant efficacy.
AB  - Since 1999, attempts have been made in the application of a new technique called
      magnetic seizure therapy (MST) or magnetic convulsion therapy (MCT) in the
      treatment of depressive disorder--as an alternative to electroconvulsive
      treatment. The technique of rapid rate transcranial magnetic stimulation (rTMS)
      is used to evoke intentional and repeated magnetoconvulsive seizures, though it
      requires the use of stimulation parameters practically inaccessible in
      commercially available rTMS magnetic stimulators. Magnetic convulsion therapy has
      been tested on monkeys as well as humans. A decisive majority of studies carried
      out both on animals and humans addressed the issue of safety of the MST method
      and confirmed that the side-effects (mostly of a cognitive nature) which occurred
      after magnetic seizures were weaker than those observed after electroconvulsive
      seizures. An analysis of available sources, however, does not confirm any proven
      antidepressant action of the MST technique. No experimental investigations have
      been carried out on animal models of depression. Clinical effectiveness had been
      confirmed in merely a few (perhaps three) patients with depression. The authors
      submit the results of the hitherto conducted studies on MST to critical analysis,
      particularly in the aspect of their antidepressant efficacy.

PMID- 20802451
TI  - Interstitial measurements of glucose, glycerol and lactate in adolescents with
      decompensated type 1 diabetes.
AB  - OBJECTIVE: The study was undertaken to assess the interstitial, adipose tissue
      concentrations of glucose, lactate and glycerol in teenagers with diabetes type 1
      who suffered from the disease for a minimum of 5 years, in whom it was impossible
      to reach a satisfactory level of metabolic control of the disease. METHODS: Using
      microdialysis technique interstitial concentrations of glucose lactate and
      glycerol was measured in adipose tissue during 24-48 hours. Nineteen teenagers
      with poorly controlled type 1 diabetes (HbA1c 8.9+/-2.85%) were compared with six
      adolescent control subjects. RESULTS: A statistically significant differences in
      concentration values of interstitial glucose between the investigated and control
      groups were found (10.4 vs. 4.26 mmol/l p=0.001). The values of interstitial
      concentrations of lactates did not significantly differ in the two groups (2.96
      vs. 2.54 mmol/l NS). The average daily glycerol concentrations in the
      investigated group were statistically significantly lower than those in the
      control group (258.26 vs. 397.88 umol/l, p=0.019). No such difference was
      detected in average night concentrations of glycerol (157.78 vs. 361.4 umol/l,
      NS). CONCLUSIONS: Authors conclude that microdialysis is the only one minimal
      invasive method for investigating adipose tissue metabolism in vivo and provides
      a novel opportunity for glucose and lipids metabolism monitoring in adolescents
      with diabetes type 1. In our observations interstitial glycerol concentrations,
      measured in abdominal subcutaneous adipose tissue as an index of lipolysis, were
      not significantly influenced by hyperglycemia in diabetic adolescents.

PMID- 20802452
TI  - Evidence to suggest glutamic acid involvement in Bisphenol A effect at the
      hypothalamic level in prepubertal male rats.
AB  - OBJECTIVES: The aim of present paper was to study the probable role of glutamic
      acid (GLU) as a mediator of bisphenol A (BPA) effect at the hypothalamic level
      and its effects on the reproductive axis of prepubertal male rats. METHODS: Mated
      Wistar rats were treated with either 0.1% ethanol (control group, n=10) or BPA
      (BPA group, n=10) in their drinking water until their offspring were weaned at
      the age of 21 days. The estimated average dose of exposure to dams was
      approximately 2.5 mg/kg body weight/day of BPA. At the prepubertal stage (35 days
      of age), the male rats were sacrificed and Gn-RH and glutamic acid (GLU) release,
      an amino acid involved in Gn-RH secretion, were measured in hypothalamic samples
      containing medio basal and anterior preoptic area (MBH-APOA), by RIA and HPLC
      respectively. LH, FSH serum levels were measured by RIA and testosterone by
      EQLIA. RESULTS: Gn-RH and GLU release decreased significantly in animals exposed
      to BPA (p<0.001, p<0.01). LH, FSH and testosterone serum levels were also
      decreased by treatment (p<0.0001). CONCLUSION: Present results provide evidence
      that BPA may act at the hypothalamic level to decrease GLU release which in turn
      may modify Gn-RH secretion altering the normal function of the axis.

PMID- 20802453
TI  - Endometrial cancer--prospective potential to make diagnostic process more
      specific.
AB  - OBJECTIVE: The incidence of carcinoma of endometrium in younger patients has
      increased tendency. Experimental data support that mutation of tumor suppressor
      gene TP53 plays an important role in endometrial carcinogenesis MATERIAL AND
      METHODS: Exons 2-11 of the gene TP53 into tissues of endometrial carcinoma and
      precancerous lesions were analyzed by DNA sequencing and restriction analysis.
      RESULTS: A polymorphism CCC/CGC at codon 72 was identified in exon 4 of TP53 gene
      of all precancerous lesions and carcinomas of endometrium. CONCLUSION: Our
      results also suggest presence of endometrial glandular dysplasia or serous
      histological type of endometrial carcinoma into examined samples. Given the
      course and prognosis of serous endometrial carcinoma, it is necessary and useful
      to identify this type of cancer in the mixed types of endometrial carcinomas. DNA
      analysis has potential to make diagnostic process more specific and affect to
      adjuvant therapy and survival of patients.

PMID- 20802454
TI  - Effects of URB597, an inhibitor of fatty acid amide hydrolase (FAAH), on
      analgesic activity of paracetamol.
AB  - OBJECTIVES: Paracetamol is converted to an active metabolite AM404 via fatty acid
      amide hydrolase (FAAH). The aim of the present study was to ascertain whether a
      FAAH inhibitor URB597 antagonizes paracetamol analgesic activity (and to asses by
      this way the role of FAAH in analgesic activity of paracetamol). METHODS: The
      interaction between a FAAH inhibitor URB597 and paracetamol was investigated in
      the writhing test in mice using an isobolographic analysis. RESULTS: URB597 or
      paracetamol alone and in combinations produced dose-dependent antinociceptive
      effects. ED50 values were estimated for the individual drugs and an isobologram
      was constructed. The observed ED50 value for the URB57-paracetamol combination
      was 0.097 (0.062-0.247) mg/kg. This value did not differ significantly from the
      theoretical additive ED50 value for the URB597-paracetamol combination which was
      0.108 (0.059-0.198) mg/kg. Thus, inhibition of FAAH by URB597 was not followed by
      the lack of analgesic activity in paracetamol. CONCLUSION: The present results
      suggest that the analgesic activity of paracetamol is not dependent solely on
      FAAH metabolic conversion to AM404 and that paracetamol exerts analgesic activity
      also by additional mechanisms.

PMID- 20802455
TI  - Effects of recombinant human growth hormone (rhGH) replacement therapy on
      detailed immunologic parameters in somatotropine--deficient paediatrics patients
      prior and after 6 months of rhGH treatment.
AB  - OBJECTIVE: This study aims at assessing how recombinant human growth hormone
      treatment of children and young people suffering from isolated growth hormone
      deficiency affects some selected parameters of the immune system: a percentage of
      lymphocytes, granulocytes, monocytes, concentrations of A, G, and M
      immunoglobulins, a percentage of T lymphocytes divided into subpopulations CD4
      and CD8, a percentage of NK and B lymphocytes, and phagocytic activity of
      granulocytes and monocytes. MATERIALS AND METHODS: The study comprised 30
      children and young people aged 4.2-18 years with isolated growth hormone
      deficiency both prior to and 6 months after rhGH (recombinant human growth
      hormone) treatment with a dose of 0.093 IU/kg every 24 hr. The control group
      comprised 25 healthy children with normal height in the respective age bracket.
      Labelling was conducted by flow cytometry FACS manufactured by Becton-Dickinson
      using both labelled antibodies and PHAGOTEST(r) commercial kit (Orpegen).
      Concentrations of A, G and M immunoglobulins in blood serum were assessed by
      means of immunoturbidimetric method using COBAS (manufactured by Roche). RESULTS:
      The lowest percentage of active granulocytes in PHAGOTEST(r) was found in a group
      examined prior to treatment compared to the control group. The percentage
      increased after 6 months of rhGH treatment to values comparable with the control
      group. Although mean concentrations of IgM and IgA after 6 months of treatment
      with rhGH significantly decreased in comparison with those determined prior to
      treatment, they still remained within the baseline norm. No significant
      differences in the phagocytic activity of monocytes, IgG concentration, % of NK
      lymphocytes, T lymphocytes divided into CD4 and CD8 lymphocytes, B lymphocytes
      and CD4/CD8 lymphocytic index were found. None of the patients exhibited any
      clinical symptoms of immune disorders. CONCLUSION: rhGH treatment of patients
      with isolated growth hormone deficiency can have positive influence on the
      phagocytic activity of scavenger cells, mainly granulocytes, which in children
      with isolated growth hormone deficiency seems to be lower than in their health
      peers. Growth hormone treatment of children with isolated growth hormone
      deficiency does not significantly affect the activity of the immune system
      expressed by the phagocytic activity of monocytes, the percentage of B, T and NK
      lymphocytes and IgG concentration in blood serum.

PMID- 20802456
TI  - Effects of growth hormone and insulin-like growth factor-I on the iron-induced
      lipid peroxidation in the rat liver and porcine thyroid homogenates.
AB  - OBJECTIVES: Growth hormone (GH) and its tissue mediator, insulin-like growth
      factor-I (IGF-I), are involved in oxidative processes, lipid peroxidation (LPO)
      included. Bivalent iron (Fe2+) is frequently used to experimentally induce
      oxidative damage to macromolecules (Fe2++H2O2+H+->Fe3++*OH+H2O). The aim of the
      study was to evaluate the effect of GH and/or IGF-I on the iron-induced LPO in
      the rat liver and porcine thyroid homogenates. METHODS: Rat liver and porcine
      thyroid homogenates were incubated in presence of GH (100; 10; 1.0; 0.1; 0.01;
      0.001; 0.0001 ug/ml) or IGF-I (1000; 100; 10; 1.0; 0.1; 0.01; 0.001; 0.0001
      ug/ml) or GH (100 ug/ml)+IGF-I, or FeSO4+H2O2 plus GH and/or IGF-I. The level of
      LPO was expressed as concentrations of malondialdehyde+4-hydroxyalkenals (MDA+4
      HDA) per mg of protein. RESULTS: GH and/or IGF-I did not change the basal level
      of oxidative damage to lipids. In the rat liver homogenates, GH did not affect
      the iron-induced LPO, whereas IGF-I--in the lowest two concentrations--enhanced
      the process. In porcine thyroid homogenates, GH--in its two lowest concentrations
      -prevented, whereas in other concentrations, it enhanced the iron-induced LPO.
      IGF-I, in all used concentrations, enhanced the iron-induced LPO. CONCLUSION: GH
      and/or IGF-I may reveal prooxidative effects. This fact does not support their
      application in the treatment of disorders associated with increased oxidative
      damage.

PMID- 20802457
TI  - Effect of chronic exposure to a GSM-like signal (mobile phone) on survival of
      female Sprague-Dawley rats: modulatory effects by month of birth and possibly
      stage of the solar cycle.
AB  - During 1997-2008 two long-term (I and II) and two life-long (III and IV)
      experiments were performed analyzing the effect of chronic exposure to a low
      intensity GSM-like signal (900 MHz pulsed with 217 Hz, 100 uW/cm2 average power
      flux density, 38-80 mW/kg mean specific absorption rate for whole body) on health
      and survival of unrestrained female Sprague-Dawley rats kept under identical
      conditions. Radiofrequency (RF)-exposure was started at 52-70 days of age and
      continued for 24 (I), 17 (II) and up to 36 and 37 months, respectively (III/IV).
      In the first two experiments (1997-2000) 12 exposed and 12 sham-exposed animals
      each were observed until they were maximally 770 or 580 days old. In experiment I
      no adverse health effects of chronic RF-exposure were detectable, neither by
      macroscopic nor detailed microscopic pathological examinations. Also in
      experiment II no apparent macroscopic pathological changes due to treatment were
      apparent. Median survival time could not be estimated since in none of the groups
      more than 50% of the animals had died. In the course of two complete survival
      experiments (2002-2005; 2005-2008) 30 RF- and 30 sham-exposed animals each were
      followed up until their natural end or when they became moribund and had to be
      euthanized. A synoptical data analysis was performed. Survival data of all four
      groups could be fitted well by the Weibull distribution. According to this
      analysis median survival was significantly shortened under RF-exposure in both
      experiments by 9.06% (95% CI 2.7 to 15.0%) (p=0.0064); i.e by 72 days in
      experiment III and 77 days in experiment IV as compared to the corresponding sham
      treated animals (III: 799 days; IV: 852 days). Both groups of animals of
      experiment III showed reduced median survival times by 6.25% (95% CI -0.3 to
      12.4%) (p=0.0604) compared to the corresponding groups of experiment IV (53 days:
      sham-exposed animals, 48 days: RF-exposed animals) which may be due to the fact
      that animals of experiment III were born in October and animals of experiment IV
      in May indicating that the month of birth affects life span. From the results of
      the last two experiments it has to be concluded that chronic exposure to a low
      intensity GSM-like signal may exert negative health effects and shorten survival
      if treatment is applied sufficiently long and the observational period covers the
      full life span of the animals concerned. The current data show that survival of
      rats kept under controlled laboratory conditions varies within certain limits
      depending on the month of birth. In view of our previous observations regarding
      an inhibitory or no effect of RF-exposure on DMBA-induced mammary cancer during
      the 1997-2000 period, an additional modulatory influence on a year-to-year basis
      should be considered which might be related to changing solar activity during the
      the 11-years' sunspot cycle. These potentially complex influences of the natural
      environment modulating the effects of anthropogenic RF-signals on health and
      survival require a systematic continuation of such experiments throughout solar
      cycle 24 which started in 2009.

PMID- 20802458
TI  - Early exposure to noise followed by predator stress in adulthood impairs the
      rat's re-learning flexibility in Radial Arm Water Maze.
AB  - OBJECTIVE: This study investigated the cognitive effect of chronic exposure to
      environmental noise on RAWM performance of juvenile rats, and the ability of
      adult rats exposed to a novel acute stress to perform in the RAWM as a function
      of whether or not they were exposed to environmental noise as juveniles. METHODS:
      We examined the consequences of exposure to noise during the juvenile-early
      periadolescent period on adulthood stress response by assessing cognitive
      performance in the RAWM. Male rats were exposed to environmental noise during the
      childhood-prepubescent period (21-35 PND), and their RAWM performance was tested
      at the end of the exposure to noise, and then again two months later when they
      had to cope with a new stressful event. RAWM execution included a 3-day training
      phase and a reversal learning phase on day 4. Escape latency, reference memory
      errors and working memory errors were compared between experimental and control
      groups. In addition, body weight gain and serum corticosterone levels were
      evaluated. RESULTS: Stressed rats demonstrated spatial impairment, as evidenced
      by poor execution on day 4. This effect was significantly noticeable in the
      doubly stressed group. Noise annoyance was evidenced by reduced body weight gain
      and increased serum corticosterone levels. CONCLUSIONS: Our results suggest that
      environmental noise may produce potent stress-like effects in developing subjects
      that can persist into adulthood, affecting spatial learning abilities. This
      cognitive impairment may restrict the subject's ability to learn under a new
      spatial configuration.

PMID- 20802459
TI  - Angiosarcoma arising within a Malignant Endovascular Papillary Angioendothelioma
      (Dabska tumor).
AB  - We report an angiosarcoma arising within a malignant endovascular papillary
      angioendothelioma (Dabska tumor) in soft tissue of the upper thigh/buttock of a
      42-year-old woman. Although neoplastic progression within a vascular tumor of an
      existing low-grade lesion into DT has been described so far, we seem to be the
      first to report transformation of DT into an angiosarcoma.

PMID- 20802460
TI  - Adipokines and genetic factors in overweight or obese but metabolically healthy
      Polish women.
AB  - OBJECTIVE: Obesity may be accompanied by enhanced metabolic disturbances but not
      all obese patients suffer from metabolic syndrome. Since metabolic homeostasis is
      under control of genetic factors underlying expression of adipokines, we aimed to
      compare the serum concentrations of adiponectin and resistin, and polymorphism in
      their genes, in overweight or obese Polish women. MATERIAL AND METHODS: The study
      included 265 women with BMI above 25 kg/m2 (140 metabolically healthy and 125
      with metabolic syndrome) and 104 non-obese women as a control group.
      Anthropometric parameters (BMI, BIA, WHR), blood pressure, lipid, glucose and
      HOMA-IR profiles as well as serum concentrations of adiponectin, HMW adiponectin
      and resistin were evaluated. Gene polymorphisms of adiponectin gene (276G/T;
      11377C/G; 11391G/A) and resistin gene (420C/G; 62G/A; 537A/C) were analyzed using
      TaqMan SNP genotyping assays. RESULTS: Higher serum concentrations of total
      adiponectin and lower levels of resistin were found in metabolically healthy
      patients when compared to those diagnosed with metabolic syndrome. No differences
      of serum HMW and resistin concentrations were observed between overweight or
      obese but metabolically healthy subjects and normal weight controls. No
      associations of investigated polymorphisms and the presence of metabolic syndrome
      were noticed in overweight/obese women with metabolic syndrome. CONCLUSIONS: The
      assessment of total adiponectin in sera seems to be promising target in
      distinguishing subjects with obesity who undergo a diagnostic procedure for
      metabolic syndrome. Moreover, the evaluation of adipokine array may help to
      select patients with higher risk of metabolic disturbances that are associated
      with severe diseases.

PMID- 20802461
TI  - beta-arrestin Kurtz inhibits MAPK and Toll signalling in Drosophila development.
AB  - beta-Arrestins have been implicated in the regulation of multiple signalling
      pathways. However, their role in organism development is not well understood. In
      this study, we report a new in vivo function of the Drosophila beta-arrestin
      Kurtz (Krz) in the regulation of two distinct developmental signalling modules:
      MAPK ERK and NF-kappaB, which transmit signals from the activated receptor
      tyrosine kinases (RTKs) and the Toll receptor, respectively. Analysis of the
      expression of effectors and target genes of Toll and the RTK Torso in krz
      maternal mutants reveals that Krz limits the activity of both pathways in the
      early embryo. Protein interaction studies suggest a previously uncharacterized
      mechanism for ERK inhibition: Krz can directly bind and sequester an inactive
      form of ERK, thus preventing its activation by the upstream kinase, MEK. A
      simultaneous dysregulation of different signalling systems in krz mutants results
      in an abnormal patterning of the embryo and severe developmental defects. Our
      findings uncover a new in vivo function of beta-arrestins and present a new
      mechanism of ERK inhibition by the Drosophila beta-arrestin Krz.

PMID- 20802462
TI  - Disulphide production by Ero1alpha-PDI relay is rapid and effectively regulated.
AB  - The molecular networks that control endoplasmic reticulum (ER) redox conditions
      in mammalian cells are incompletely understood. Here, we show that after
      reductive challenge the ER steady-state disulphide content is restored on a time
      scale of seconds. Both the oxidase Ero1alpha and the oxidoreductase protein
      disulphide isomerase (PDI) strongly contribute to the rapid recovery kinetics,
      but experiments in ERO1-deficient cells indicate the existence of parallel
      pathways for disulphide generation. We find PDI to be the main substrate of
      Ero1alpha, and mixed-disulphide complexes of Ero1 primarily form with PDI, to a
      lesser extent with the PDI-family members ERp57 and ERp72, but are not detectable
      with another homologue TMX3. We also show for the first time that the oxidation
      level of PDIs and glutathione is precisely regulated. Apparently, this is
      achieved neither through ER import of thiols nor by transport of disulphides to
      the Golgi apparatus. Instead, our data suggest that a dynamic equilibrium between
      Ero1- and glutathione disulphide-mediated oxidation of PDIs constitutes an
      important element of ER redox homeostasis.

PMID- 20802464
TI  - Cell cycle coordination and regulation of bacterial chromosome segregation
      dynamics by polarly localized proteins.
AB  - What regulates chromosome segregation dynamics in bacteria is largely unknown.
      Here, we show in Caulobacter crescentus that the polarity factor TipN regulates
      the directional motion and overall translocation speed of the parS/ParB partition
      complex by interacting with ParA at the new pole. In the absence of TipN, ParA
      structures can regenerate behind the partition complex, leading to stalls and
      back-and-forth motions of parS/ParB, reminiscent of plasmid behaviour. This
      extrinsic regulation of the parS/ParB/ParA system directly affects not only
      division site selection, but also cell growth. Other mechanisms, including the
      pole-organizing protein PopZ, compensate for the defect in segregation regulation
      in DeltatipN cells. Accordingly, synthetic lethality of PopZ and TipN is caused
      by severe chromosome segregation and cell division defects. Our data suggest a
      mechanistic framework for adapting a self-organizing oscillator to create motion
      suitable for chromosome segregation.

PMID- 20802465
TI  - Array-based comparative genomic hybridization in ulcerative colitis neoplasia:
      single non-dysplastic biopsies distinguish progressors from non-progressors.
AB  - Approximately 10% of ulcerative colitis patients develop colorectal neoplasia. At
      present, identification of this subset is markedly limited and necessitates
      lifelong colonoscopic surveillance for the entire ulcerative colitis population.
      Better risk markers are needed to focus surveillance onto the patients who are
      most likely to benefit. Using array-based comparative genomic hybridization, we
      analyzed single, non-dysplastic biopsies from three patient groups: ulcerative
      colitis progressors (n=9) with cancer or high-grade dysplasia at a mean distance
      of 18 cm from the analyzed site; ulcerative colitis non-progressors (n=8) without
      dysplasia during long-term surveillance; and non-ulcerative colitis normal
      controls (n=2). Genomic DNA from fresh colonic epithelium purified from stroma
      was hybridized to 287 (low-density) and 4342 (higher-density) feature bacterial
      artificial chromosome arrays. Sample-to-reference fluorescence ratios were
      calculated for individual chromosomal targets and globally across the genome. The
      low-density arrays yielded pronounced genomic gains and losses in 3 of 9 (33%)
      ulcerative colitis progressors but in none of the 10 control patients. Identical
      DNA samples analyzed on the higher-density arrays, using a combination of global
      and individual high variance assessments, distinguished all nine progressors from
      all 10 controls. These data confirm that genomic alterations in ulcerative
      colitis progressors are widespread, even involving single non-dysplastic biopsies
      that are far distant from neoplasia. They therefore show promise toward
      eliminating full colonoscopic surveillance with extensive biopsy sampling in the
      majority of ulcerative colitis patients.

PMID- 20802463
TI  - ATR and ATM differently regulate WRN to prevent DSBs at stalled replication forks
      and promote replication fork recovery.
AB  - Accurate response to replication arrest is crucial to preserve genome stability
      and requires both the ATR and ATM functions. The Werner syndrome protein (WRN) is
      implicated in the recovery of stalled replication forks, and although an ATR/ATM
      dependent phosphorylation of WRN was observed after replication arrest, the
      function of such modifications during the response to perturbed replication is
      not yet appreciated. Here, we report that WRN is directly phosphorylated by ATR
      at multiple C-terminal S/TQ residues. Suppression of ATR-mediated phosphorylation
      of WRN prevents proper accumulation of WRN in nuclear foci, co-localisation with
      RPA and causes breakage of stalled forks. On the other hand, inhibition of ATM
      kinase activity or expression of an ATM-unphosphorylable WRN allele leads to
      retention of WRN in nuclear foci and impaired recruitment of RAD51 recombinase
      resulting in reduced viability after fork collapse. Altogether, our findings
      indicate that ATR and ATM promote recovery from perturbed replication by
      differently regulating WRN at defined moments of the response to replication fork
      arrest.

PMID- 20802466
TI  - International Society of Urological Pathology (ISUP) consensus conference on
      handling and staging of radical prostatectomy specimens: rationale and
      organization.
AB  - The 2009 International Society of Urological Pathology consensus conference in
      Boston, made recommendations regarding the standardization of pathology reporting
      of radical prostatectomy specimens. The activities of the conference were
      coordinated through five workgroups. The results are presented in five separate
      reports covering (1) specimen handling, (2) T2 substaging and prostate cancer
      volume, (3) extraprostatic extension, lymphovascular invasion and locally
      advanced disease, (4) seminal vesicles and lymph node metastases and (5) surgical
      margins. In this introductory article we describe some novel features of the
      organization of the consensus process. Following the completion of a pre-meeting
      survey conference, participants discussed and voted on 43 specific issues of
      contention relating to the pathological reporting of radical prostatectomy
      specimens. Consensus, defined as agreement by at least 65% of participants
      present, was achieved for 30 questions.

PMID- 20802468
TI  - Pancreatic lymphoepithelial cysts express CEA and can contain mucous cells:
      potential pitfalls in the preoperative diagnosis.
AB  - Pancreatic lymphoepithelial cysts are rare benign cysts that cannot be reliably
      differentiated from neoplastic mucinous cysts preoperatively. Although elevated
      cyst fluid carcinoembryonic antigen (CEA) levels support a diagnosis of a
      mucinous cyst, the finding of increased CEA levels in lymphoepithelial cysts
      prompted this study. Nine resected lymphoepithelial cysts were examined for
      expression of CEA, carbohydrate antigen (CA) 19-9, CK7, p63, PAS-D and a panel of
      mucins. The pathology data were correlated with clinical information, including
      serum, cyst fluid and imaging studies. By computed tomography scan, although most
      lymphoepithelial cysts appeared cystic, 23% were described as masses. The
      endoscopic ultrasound findings were variable, but the lymphoepithelial cysts
      tended to be hypoechoic cystic lesions or masses. On cytology, 44% of the cysts
      had squamous cells, 67% had glandular cells and 56% had atypical cells. The cysts
      were resected because of size >=3 cm (89%), symptoms (44%) and/or elevated cyst
      fluid CEA levels (33%). The cyst fluid CEA levels in the three cysts tested were
      >450 ng/ml. Histopathologically, all cysts were lined by mature, stratified
      squamous-type cells and produced keratin. Mucous cells were present in 78% of the
      cysts. The immunohistochemical profile of the squamous lining was CK7+, p63+,
      MUC1+, MUC4+, MUC2-, MUC5AC- and MUC6-. Even though lymphoepithelial cysts are
      lined by squamous-type epithelium, all our resected lymphoepithelial cysts
      expressed CEA and/or CA19-9, many contained mucous cells, and three exhibited
      markedly elevated cyst fluid CEA levels. Although cyst fluid CEA levels >200
      ng/ml support the diagnosis of mucinous neoplasms, this study emphasizes the need
      for clinicians and pathologists to recognize that lymphoepithelial cysts can
      mimic neoplastic mucinous cysts clinically, radiographically and on cyst fluid
      CEA analysis.

PMID- 20802469
TI  - Detection of chromosome copy number alterations in metanephric adenomas by array
      comparative genomic hybridization.
AB  - Metanephric adenoma is a rare benign renal tumor typically found in adults.
      Previous cytogenetic analyses, including karyotyping, fluorescence in situ
      hybridization (FISH), and comparative genomic hybridization, have yielded
      conflicting results regarding the somatic genetic aberrations of these tumors. In
      this study, we investigated the genomic profile of nine cases of metanephric
      adenoma using array comparative genomic hybridization. Two cases revealed
      multiple chromosomal gains and losses. Three cases showed sporadic chromosomal
      imbalances involving no more than three chromosomes. Four cases showed normal
      chromosome copy numbers. The gain of chromosome 19 was the most common finding
      (five cases), and FISH using 19p and 19q telomeric probes further confirmed this
      finding. We did not observe consistent gains of chromosomes 7 and 17, which are
      common in papillary renal cell carcinoma, neither did we find chromosomal
      alterations frequently present in Wilms' tumors, including chromosome gains of
      1q, 7q, and 12, and losses of 11p and 16q. Our series demonstrates that the
      genetic profile of metanephric adenoma is fundamentally distinct from those of
      papillary renal cell carcinoma and Wilms' tumor.

PMID- 20802467
TI  - International Society of Urological Pathology (ISUP) Consensus Conference on
      Handling and Staging of Radical Prostatectomy Specimens. Working group 3:
      extraprostatic extension, lymphovascular invasion and locally advanced disease.
AB  - The International Society of Urological Pathology Consensus Conference on
      Handling and Staging of Radical Prostatectomy Specimens in Boston made
      recommendations regarding the standardization of pathology reporting of radical
      prostatectomy specimens. Issues relating to extraprostatic extension (pT3a
      disease), bladder neck invasion, lymphovascular invasion and the definition of
      pT4 were coordinated by working group 3. It was agreed that prostate cancer can
      be categorized as pT3a in the absence of adipose tissue involvement when cancer
      bulges beyond the contour of the gland or beyond the condensed smooth muscle of
      the prostate at posterior and posterolateral sites. Extraprostatic extension can
      also be identified anteriorly. It was agreed that the location of extraprostatic
      extension should be reported. Although there was consensus that the amount of
      extraprostatic extension should be quantitated, there was no agreement as to
      which method of quantitation should be employed. There was overwhelming consensus
      that microscopic urinary bladder neck invasion by carcinoma should be reported as
      stage pT3a and that lymphovascular invasion by carcinoma should be reported. It
      is recommended that these elements are considered in the development of practice
      guidelines and in the daily practice of urological surgical pathology.

PMID- 20802470
TI  - E2A-positive gastric MALT lymphoma has weaker plasmacytoid infiltrates and
      stronger expression of the memory B-cell-associated miR-223: possible correlation
      with stage and treatment response.
AB  - Extranodal marginal-zone lymphoma of mucosa-associated lymphoid tissue of the
      stomach (gastric MALT lymphoma) is derived from memory B cells of the marginal
      zone. Normal memory B cells do not express markers of germinal-center B cells,
      such as E2A (immunoglobulin enhancer-binding factor E12/E47), B-cell chronic
      lymphocytic leukemia/lymphoma 6 (BCL6), or activation-induced cytidine deaminase
      (AID). E2A is a transcription factor that induces somatic hypermutations and
      blocks plasma cell differentiation. In 50 stage-I(E)/II(E1) gastric MALT
      lymphomas, we confirmed that all cases were BCL6(-)/AID(-), but a subset (50%,
      25/50) was E2A(+). As E2A(-) and E2A(+) gastric MALT lymphomas had similar
      numbers of somatic hypermutations without intraclonal variations, which implied
      an origin from memory B cells, the expression of E2A was best regarded as a
      marker of aberrant follicular differentiation. Although the status of somatic
      hypermutation was not affected by E2A, E2A(+) gastric MALT lymphoma showed less
      plasmacytoid infiltrates and higher expressions of miRNA-223, a microRNA
      associated with memory B cells. Clinically, E2A(+) gastric MALT lymphomas were
      more likely to spread to perigastric lymph nodes and were less responsive to
      Helicobacter eradication therapy than were E2A(-) gastric MALT lymphomas. Taken
      together, aberrant E2A expression is a diagnostic feature of a subtype of gastric
      MALT lymphoma with weaker plasmacytoid infiltrates and stronger miR-223
      expression. A prospective study would be necessary to verify the association
      between E2A expression and a poor response to Helicobacter eradication therapy.

PMID- 20802473
TI  - Infectious diseases not immune to genome-wide association.
AB  - Two genome-wide association studies for meningococcal disease and tuberculosis
      identify new loci associated with susceptibility to these infectious diseases.
      They highlight a role for the acquired and innate immune systems in host control
      of several human pathogens and demonstrate that denser genotyping platforms and
      population-specific reference panels are necessary for genetic studies in African
      populations.

PMID- 20802471
TI  - Postmortem findings in eight cases of influenza A/H1N1.
AB  - In March and early April 2009, cases of a new swine-origin influenza A (H1N1)
      virus were diagnosed in Mexico and the United States. Influenza virus presents as
      a respiratory infection with high morbidity and mortality. We describe the
      postmortem findings of eight confirmed cases of influenza A/H1N1 in a medical
      examiner setting. The eight cases falling under the jurisdiction of the Harris
      County Medical Examiner (Houston, TX, USA) with confirmed influenza A/H1N1
      infection between June and September 2009 were included in this study. All cases
      were males between 6 months and 54 years of age. All adult patients had a body
      mass index from 31 to 49.8 kg/m(2). Five cases had comorbid conditions including
      one case with sleep apnea and mental retardation, three cases with chronic
      ethanolism, and one case with thymoma, sarcoidosis, and myasthenia gravis. The
      remaining three cases had no pre-existing medical conditions. All patients
      presented with severe flu-like symptoms; yet, only five were febrile. Rapid
      influenza diagnostic tests were performed in three cases by primary-care
      physicians, two of which were negative. None of the patients received antiviral
      medication. The average disease duration time was 8.2 days (3-14 days). A wide
      range of histopathological findings including tracheitis, necrotizing
      bronchiolitis, alveolitis, intra-alveolar hemorrhage, and hyaline membranes, both
      in a focal and in a diffuse distribution, were identified. Influenza A/H1N1 viral
      infection presents with a wide range of histological findings in a diffuse or
      focal distribution; most consistently with tracheitis, necrotizing bronchiolitis,
      and alveolitis with extensive alveolar hemorrhage. These histopathological
      findings at autopsy along with a clinical history of flu-like symptoms should
      raise suspicion for influenza A/H1N1 infection, and postmortem analysis by the
      reverse transcription-polymerase chain reaction (RT-PCR) is recommended for an
      accurate diagnosis.

PMID- 20802474
TI  - Putting a finger on the switch.
AB  - The transition from fetal to adult beta-like globin expression is a key step in
      the maturation of the red blood cell lineage. Two new studies show that the KLF1
      zinc finger protein uses direct and indirect means to regulate the final switch
      from fetal to adult globin expression and that monoallelic loss of KLF1
      expression leads to persistence of fetal hemoglobin.

PMID- 20802475
TI  - Variable evolutionary signatures at the heart of enhancers.
AB  - What is the best way to identify regulatory DNA sequences such as enhancers,
      promoters, insulators and silencers? A new study shows that specific binding by a
      coactivator protein identifies enhancers that are invisible to common detection
      methods based on evolutionary constraint.

PMID- 20802478
TI  - Identity-by-descent filtering of exome sequence data identifies PIGV mutations in
      hyperphosphatasia mental retardation syndrome.
AB  - Hyperphosphatasia mental retardation (HPMR) syndrome is an autosomal recessive
      form of mental retardation with distinct facial features and elevated serum
      alkaline phosphatase. We performed whole-exome sequencing in three siblings of a
      nonconsanguineous union with HPMR and performed computational inference of
      regions identical by descent in all siblings to establish PIGV, encoding a member
      of the GPI-anchor biosynthesis pathway, as the gene mutated in HPMR. We
      identified homozygous or compound heterozygous mutations in PIGV in three
      additional families.

PMID- 20802477
TI  - The genome of the domesticated apple (Malus * domestica Borkh.).
AB  - We report a high-quality draft genome sequence of the domesticated apple (Malus *
      domestica). We show that a relatively recent (>50 million years ago) genome-wide
      duplication (GWD) has resulted in the transition from nine ancestral chromosomes
      to 17 chromosomes in the Pyreae. Traces of older GWDs partly support the
      monophyly of the ancestral paleohexaploidy of eudicots. Phylogenetic
      reconstruction of Pyreae and the genus Malus, relative to major Rosaceae taxa,
      identified the progenitor of the cultivated apple as M. sieversii. Expansion of
      gene families reported to be involved in fruit development may explain formation
      of the pome, a Pyreae-specific false fruit that develops by proliferation of the
      basal part of the sepals, the receptacle. In apple, a subclade of MADS-box genes,
      normally involved in flower and fruit development, is expanded to include 15
      members, as are other gene families involved in Rosaceae-specific metabolism,
      such as transport and assimilation of sorbitol.

PMID- 20802480
TI  - The ratio of human X chromosome to autosome diversity is positively correlated
      with genetic distance from genes.
AB  - The ratio of X-linked to autosomal diversity was estimated from an analysis of
      six human genome sequences and found to deviate from the expected value of 0.75.
      However, the direction of this deviation depends on whether a particular sequence
      is close to or far from the nearest gene. This pattern may be explained by
      stronger locally acting selection on X-linked genes compared with autosomal
      genes, combined with larger effective population sizes for females than for
      males.

PMID- 20802479
TI  - Genome-wide association study of migraine implicates a common susceptibility
      variant on 8q22.1.
AB  - Migraine is a common episodic neurological disorder, typically presenting with
      recurrent attacks of severe headache and autonomic dysfunction. Apart from rare
      monogenic subtypes, no genetic or molecular markers for migraine have been
      convincingly established. We identified the minor allele of rs1835740 on
      chromosome 8q22.1 to be associated with migraine (P = 5.38 * 10-9, odds ratio =
      1.23, 95% CI 1.150-1.324) in a genome-wide association study of 2,731 migraine
      cases ascertained from three European headache clinics and 10,747 population
      matched controls. The association was replicated in 3,202 cases and 40,062
      controls for an overall meta-analysis P value of 1.69 * 10-11 (odds ratio = 1.18,
      95% CI 1.127-1.244). rs1835740 is located between MTDH (astrocyte elevated gene
      1, also known as AEG-1) and PGCP (encoding plasma glutamate carboxypeptidase). In
      an expression quantitative trait study in lymphoblastoid cell lines, transcript
      levels of the MTDH were found to have a significant correlation to rs1835740 (P =
      3.96 * 10-5, permuted threshold for genome-wide significance 7.7 * 10-5. To our
      knowledge, our data establish rs1835740 as the first genetic risk factor for
      migraine.

PMID- 20802481
TI  - Identification of a quality-control mechanism for mRNA 5'-end capping.
AB  - The 7-methylguanosine cap structure at the 5' end of eukaryotic messenger RNAs is
      a critical determinant of their stability and translational efficiency. It is
      generally believed that 5'-end capping is a constitutive process that occurs
      during mRNA maturation and lacks the need for a quality-control mechanism to
      ensure its fidelity. We recently reported that the yeast Rai1 protein has
      pyrophosphohydrolase activity towards mRNAs lacking a 5'-end cap. Here we show
      that, in vitro as well as in yeast cells, Rai1 possesses a novel decapping
      endonuclease activity that can also remove the entire cap structure dinucleotide
      from an mRNA. This activity is targeted preferentially towards mRNAs with
      unmethylated caps in contrast to the canonical decapping enzyme, Dcp2, which
      targets mRNAs with a methylated cap. Capped but unmethylated mRNAs generated in
      yeast cells with a defect in the methyltransferase gene are more stable in a rai1
      gene-disrupted background. Moreover, rai1Delta yeast cells with wild-type capping
      enzymes show significant accumulation of mRNAs with 5'-end capping defects under
      nutritional stress conditions of glucose starvation or amino acid starvation.
      These findings provide evidence that 5'-end capping is not a constitutive process
      that necessarily always proceeds to completion and demonstrates that Rai1 has an
      essential role in clearing mRNAs with aberrant 5'-end caps. We propose that Rai1
      is involved in an as yet uncharacterized quality control process that ensures
      mRNA 5'-end integrity by an aberrant-cap-mediated mRNA decay mechanism.

PMID- 20802482
TI  - The transcription cofactor Hopx is required for regulatory T cell function in
      dendritic cell-mediated peripheral T cell unresponsiveness.
AB  - Induced regulatory T cells (iT(reg) cells) can be generated by peripheral
      dendritic cells (DCs) that mediate T cell unresponsiveness to rechallenge with
      antigen. The molecular factors required for the function of such iT(reg) cells
      remain unknown. We report a critical role for the transcription cofactor
      homeodomain-only protein (Hop; also known as Hopx) in iT(reg) cells to mediate T
      cell unresponsiveness in vivo. Hopx-sufficient iT(reg) cells downregulated
      expression of the transcription factor AP-1 complex and suppressed other T cells.
      In the absence of Hopx, iT(reg) cells had high expression of the AP-1 complex,
      proliferated and failed to mediate T cell unresponsiveness to rechallenge with
      antigen. Thus, Hopx is required for the function of T(reg) cells induced by DCs
      and the promotion of DC-mediated T cell unresponsiveness in vivo.

PMID- 20802483
TI  - Structural insights into the assembly and activation of IL-1beta with its
      receptors.
AB  - Interleukin 1beta (IL-1beta) is a key orchestrator of inflammation and host
      defense that exerts its effects through IL-1 receptor type I (IL-1RI) and IL-1
      receptor accessory protein (IL-1RAcP). How IL-1RAcP is recruited by IL-1beta-IL
      1RI to form the signaling-competent complex remains elusive. Here we present the
      crystal structure of IL-1beta bound to IL-1 receptor type II (IL-1RII) and IL
      1RAcP. IL-1beta-IL-1RII generated a composite binding surface to recruit IL
      1RAcP. Biochemical analysis demonstrated that IL-1beta-IL-1RI and IL-1beta-IL
      1RII interacted similarly with IL-1RAcP. It also showed the importance of two
      loops of IL-1 receptor antagonist (IL-1Ra) in determining its antagonism. Our
      results provide a structural basis for assembly and activation of the IL-1
      receptor and offer a general cytokine-receptor architecture that governs the IL-1
      family of cytokines.

PMID- 20802484
TI  - Complement-mediated regulation of the IL-17A axis is a central genetic
      determinant of the severity of experimental allergic asthma.
AB  - Severe asthma is associated with the production of interleukin 17A (IL-17A). The
      exact role of IL-17A in severe asthma and the factors that drive its production
      are unknown. Here we demonstrate that IL-17A mediated severe airway
      hyperresponsiveness (AHR) in susceptible strains of mice by enhancing IL-13
      driven responses. Mechanistically, we demonstrate that IL-17A and AHR were
      regulated by allergen-driven production of anaphylatoxins, as mouse strains
      deficient in complement factor 5 (C5) or the complement receptor C5aR mounted
      robust IL-17A responses, whereas mice deficient in C3aR had fewer IL-17-producing
      helper T cells (T(H)17 cells) and less AHR after allergen challenge. The opposing
      effects of C3a and C5a were mediated through their reciprocal regulation of IL-23
      production. These data demonstrate a critical role for complement-mediated
      regulation of the IL-23-T(H)17 axis in severe asthma.

PMID- 20802485
TI  - Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA
      nonhomologous end-joining.
AB  - DNA double-strand break (DSB) repair occurs within chromatin and can be modulated
      by chromatin-modifying enzymes. Here we identify the related human histone
      deacetylases HDAC1 and HDAC2 as two participants in the DNA-damage response. We
      show that acetylation of histone H3 Lys56 (H3K56) was regulated by HDAC1 and
      HDAC2 and that HDAC1 and HDAC2 were rapidly recruited to DNA-damage sites to
      promote hypoacetylation of H3K56. Furthermore, HDAC1- and 2-depleted cells were
      hypersensitive to DNA-damaging agents and showed sustained DNA-damage signaling,
      phenotypes that reflect defective DSB repair, particularly by nonhomologous end
      joining (NHEJ). Collectively, these results show that HDAC1 and HDAC2 function in
      the DNA-damage response by promoting DSB repair and thus provide important
      insights into the radio-sensitizing effects of HDAC inhibitors that are being
      developed as cancer therapies.

PMID- 20802486
TI  - Structural basis of quinolone inhibition of type IIA topoisomerases and target
      mediated resistance.
AB  - Quinolone antibacterials have been used to treat bacterial infections for over 40
      years. A crystal structure of moxifloxacin in complex with Acinetobacter
      baumannii topoisomerase IV now shows the wedge-shaped quinolone stacking between
      base pairs at the DNA cleavage site and binding conserved residues in the DNA
      cleavage domain through chelation of a noncatalytic magnesium ion. This provides
      a molecular basis for the quinolone inhibition mechanism, resistance mutations
      and invariant quinolone antibacterial structural features.

PMID- 20802487
TI  - Solid-state NMR and SAXS studies provide a structural basis for the activation of
      alphaB-crystallin oligomers.
AB  - The small heat shock protein alphaB-crystallin (alphaB) contributes to cellular
      protection against stress. For decades, high-resolution structural studies on
      oligomeric alphaB have been confounded by its polydisperse nature. Here, we
      present a structural basis of oligomer assembly and activation of the chaperone
      using solid-state NMR and small-angle X-ray scattering (SAXS). The basic building
      block is a curved dimer, with an angle of approximately 121 degrees between the
      planes of the beta-sandwich formed by alpha-crystallin domains. The highly
      conserved IXI motif covers a substrate binding site at pH 7.5. We observe a pH
      dependent modulation of the interaction of the IXI motif with beta4 and beta8,
      consistent with a pH-dependent regulation of the chaperone function. N-terminal
      region residues Ser59-Trp60-Phe61 are involved in intermolecular interaction with
      beta3. Intermolecular restraints from NMR and volumetric restraints from SAXS
      were combined to calculate a model of a 24-subunit alphaB oligomer with
      tetrahedral symmetry.

PMID- 20802488
TI  - Chemical-genomic dissection of the CTD code.
AB  - Sequential modifications of the RNA polymerase II (Pol II) C-terminal domain
      (CTD) coordinate the stage-specific association and release of cellular machines
      during transcription. Here we examine the genome-wide distributions of the
      'early' (phospho-Ser5 (Ser5-P)), 'mid' (Ser7-P) and 'late' (Ser2-P) CTD marks. We
      identify gene class-specific patterns and find widespread co-occurrence of the
      CTD marks. Contrary to its role in 3'-processing of noncoding RNA, the Ser7-P
      marks are placed early and retained until transcription termination at all Pol II
      dependent genes. Chemical-genomic analysis reveals that the promoter-distal Ser7
      P marks are not remnants of early phosphorylation but are placed anew by the CTD
      kinase Bur1. Consistent with the ability of Bur1 to facilitate transcription
      elongation and suppress cryptic transcription, high levels of Ser7-P are observed
      at highly transcribed genes. We propose that Ser7-P could facilitate elongation
      and suppress cryptic transcription.

PMID- 20802489
TI  - Intrinsic biophysical diversity decorrelates neuronal firing while increasing
      information content.
AB  - Although examples of variation and diversity exist throughout the nervous system,
      their importance remains a source of debate. Even neurons of the same molecular
      type have notable intrinsic differences. Largely unknown, however, is the degree
      to which these differences impair or assist neural coding. We examined the
      outputs from a single type of neuron, the mitral cells of the mouse olfactory
      bulb, to identical stimuli and found that each cell's spiking response was
      dictated by its unique biophysical fingerprint. Using this intrinsic
      heterogeneity, diverse populations were able to code for twofold more information
      than their homogeneous counterparts. In addition, biophysical variability alone
      reduced pair-wise output spike correlations to low levels. Our results indicate
      that intrinsic neuronal diversity is important for neural coding and is not
      simply the result of biological imprecision.

PMID- 20802490
TI  - Plk2 attachment to NSF induces homeostatic removal of GluA2 during chronic
      overexcitation.
AB  - Trafficking of AMPA receptors (AMPARs) is important for many forms of synaptic
      plasticity. However, the link between activity and resulting synaptic alterations
      is not fully understood. We identified a direct interaction between N
      ethylmaleimide-sensitive fusion protein (NSF), an ATPase involved in membrane
      fusion events and stabilization of surface AMPARs, and Polo-like kinase- 2
      (Plk2), an activity-inducible kinase that homeostatically decreases excitatory
      synapse number and strength. Plk2 disrupted the interaction of NSF with the GluA2
      subunit of AMPARs, promoting extensive loss of surface GluA2 in rat hippocampal
      neurons, greater association of GluA2 with adaptor proteins PICK1 and GRIP1, and
      decreased synaptic AMPAR current. Plk2 engagement of NSF, but not Plk2 kinase
      activity, was required for this mechanism and occurred through a motif in the
      Plk2 protein that was independent of the canonical polo box interaction sites.
      These data reveal that heightened synaptic activity, acting through Plk2, leads
      to homeostatic decreases in surface AMPAR expression via the direct dissociation
      of NSF from GluA2.

PMID- 20802491
TI  - Engineered diubiquitin synthesis reveals Lys29-isopeptide specificity of an OTU
      deubiquitinase.
AB  - Ubiquitination is a reversible post-translational modification that regulates a
      myriad of eukaryotic functions. Our ability to study the effects of
      ubiquitination is often limited by the inaccessibility of homogeneously
      ubiquitinated proteins. In particular, elucidating the roles of the so-called
      'atypical' ubiquitin chains (chains other than Lys48- or Lys63-linked ubiquitin),
      which account for a large fraction of ubiquitin polymers, is challenging because
      the enzymes for their biosynthesis are unknown. Here we combine genetic code
      expansion, intein chemistry and chemoselective ligations to synthesize 'atypical'
      ubiquitin chains. We solve the crystal structure of Lys6-linked diubiquitin,
      which is distinct from that of structurally characterized ubiquitin chains,
      providing a molecular basis for the different biological functions this linkage
      may regulate. Moreover, we profile a panel containing 10% of the known human
      deubiquitinases on Lys6- and Lys29-linked ubiquitin and discover that TRABID
      cleaves the Lys29 linkage 40-fold more efficiently than the Lys63 linkage.

PMID- 20802492
TI  - Tah18 transfers electrons to Dre2 in cytosolic iron-sulfur protein biogenesis.
AB  - Cytosolic and nuclear iron-sulfur (Fe-S) proteins play key roles in processes
      such as ribosome maturation, transcription and DNA repair-replication. For
      biosynthesis of their Fe-S clusters, a dedicated cytosolic Fe-S protein assembly
      (CIA) machinery is required. Here, we identify the essential flavoprotein Tah18
      as a previously unrecognized CIA component and show by cell biological,
      biochemical and spectroscopic approaches that the complex of Tah18 and the CIA
      protein Dre2 is part of an electron transfer chain functioning in an early step
      of cytosolic Fe-S protein biogenesis. Electrons are transferred from NADPH via
      the FAD- and FMN-containing Tah18 to the Fe-S clusters of Dre2. This electron
      transfer chain is required for assembly of target but not scaffold Fe-S proteins,
      suggesting a need for reduction in the generation of stably inserted Fe-S
      clusters. The pathway is conserved in eukaryotes, as human Ndor1-Ciapin1 proteins
      can functionally replace yeast Tah18-Dre2.

PMID- 20802493
TI  - Nanoscale mapping of ion diffusion in a lithium-ion battery cathode.
AB  - The movement of lithium ions into and out of electrodes is central to the
      operation of lithium-ion batteries. Although this process has been extensively
      studied at the device level, it remains insufficiently characterized at the
      nanoscale level of grain clusters, single grains and defects. Here, we probe the
      spatial variation of lithium-ion diffusion times in the battery-cathode material
      LiCoO(2) at a resolution of ~100 nm by using an atomic force microscope to both
      redistribute lithium ions and measure the resulting cathode deformation. The
      relationship between diffusion and single grains and grain boundaries is
      observed, revealing that the diffusion coefficient increases for certain grain
      orientations and single-grain boundaries. This knowledge provides feedback to
      improve understanding of the nanoscale mechanisms underpinning lithium-ion
      battery operation.

PMID- 20802494
TI  - In vitro assembly of cubic RNA-based scaffolds designed in silico.
AB  - The organization of biological materials into versatile three-dimensional
      assemblies could be used to build multifunctional therapeutic scaffolds for use
      in nanomedicine. Here, we report a strategy to design three-dimensional nanoscale
      scaffolds that can be self-assembled from RNA with precise control over their
      shape, size and composition. These cubic nanoscaffolds are only approximately 13
      nm in diameter and are composed of short oligonucleotides, making them amenable
      to chemical synthesis, point modifications and further functionalization.
      Nanocube assembly is verified by gel assays, dynamic light scattering and
      cryogenic electron microscopy. Formation of functional RNA nanocubes is also
      demonstrated by incorporation of a light-up fluorescent RNA aptamer that is
      optimally active only upon full RNA assembly. Moreover, we show that the RNA
      nanoscaffolds can self-assemble in isothermal conditions (37 degrees C) during in
      vitro transcription, which opens a route towards the construction of sensors,
      programmable packaging and cargo delivery systems for biomedical applications.

PMID- 20802495
TI  - Monoclonal antibodies isolated without screening by analyzing the variable-gene
      repertoire of plasma cells.
AB  - Isolation of antigen-specific monoclonal antibodies (mAbs) and antibody fragments
      relies on high-throughput screening of immortalized B cells or recombinant
      antibody libraries. We bypassed the screening step by using high-throughput DNA
      sequencing and bioinformatic analysis to mine antibody variable region (V)-gene
      repertoires from bone marrow plasma cells (BMPC) of immunized mice. BMPCs, which
      cannot be immortalized, produce the vast majority of circulating antibodies. We
      found that the V-gene repertoire of BMPCs becomes highly polarized after
      immunization, with the most abundant sequences represented at frequencies between
      approximately 1% and >10% of the total repertoire. We paired the most abundant
      variable heavy (V(H)) and variable light (V(L)) genes based on their relative
      frequencies, reconstructed them using automated gene synthesis, and expressed
      recombinant antibodies in bacteria or mammalian cells. Antibodies generated in
      this manner from six mice, each immunized with one of three antigens were
      overwhelmingly antigen specific (21/27 or 78%). Those generated from a mouse with
      high serum titers had nanomolar binding affinities.

PMID- 20802496
TI  - De novo identification and biophysical characterization of transcription-factor
      binding sites with microfluidic affinity analysis.
AB  - Gene expression is regulated in part by protein transcription factors that bind
      target regulatory DNA sequences. Predicting DNA binding sites and affinities from
      transcription factor sequence or structure is difficult; therefore, experimental
      data are required to link transcription factors to target sequences. We present a
      microfluidics-based approach for de novo discovery and quantitative biophysical
      characterization of DNA target sequences. We validated our technique by measuring
      sequence preferences for 28 Saccharomyces cerevisiae transcription factors with a
      variety of DNA-binding domains, including several that have proven difficult to
      study by other techniques. For each transcription factor, we measured relative
      binding affinities to oligonucleotides covering all possible 8-bp DNA sequences
      to create a comprehensive map of sequence preferences; for four transcription
      factors, we also determined absolute affinities. We expect that these data and
      future use of this technique will provide information essential for understanding
      transcription factor specificity, improving identification of regulatory sites
      and reconstructing regulatory interactions.

PMID- 20802497
TI  - High-throughput generation, optimization and analysis of genome-scale metabolic
      models.
AB  - Genome-scale metabolic models have proven to be valuable for predicting organism
      phenotypes from genotypes. Yet efforts to develop new models are failing to keep
      pace with genome sequencing. To address this problem, we introduce the Model
      SEED, a web-based resource for high-throughput generation, optimization and
      analysis of genome-scale metabolic models. The Model SEED integrates existing
      methods and introduces techniques to automate nearly every step of this process,
      taking approximately 48 h to reconstruct a metabolic model from an assembled
      genome sequence. We apply this resource to generate 130 genome-scale metabolic
      models representing a taxonomically diverse set of bacteria. Twenty-two of the
      models were validated against available gene essentiality and Biolog data, with
      the average model accuracy determined to be 66% before optimization and 87% after
      optimization.

PMID- 20802498
TI  - Adaptation of HIV-1 envelope gp120 to humoral immunity at a population level.
AB  - By comparing HIV-1 variants from people who became infected at the beginning of
      the epidemic and from people who have recently contracted the virus, we observed
      an enhanced resistance of the virus to antibody neutralization over time,
      accompanied by an increase in the length of the variable loops and in the number
      of potential N-linked glycosylation sites on the HIV-1 envelope gp120 subunit.
      The enhanced neutralization resistance of HIV-1 in contemporary seroconverters
      coincided with the poorer elicitation of neutralizing antibody responses, which
      may have implications for vaccine design.

PMID- 20802499
TI  - Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy
      balance.
AB  - Thyroid hormones have widespread cellular effects; however it is unclear whether
      their effects on the central nervous system (CNS) contribute to global energy
      balance. Here we demonstrate that either whole-body hyperthyroidism or central
      administration of triiodothyronine (T3) decreases the activity of hypothalamic
      AMP-activated protein kinase (AMPK), increases sympathetic nervous system (SNS)
      activity and upregulates thermogenic markers in brown adipose tissue (BAT).
      Inhibition of the lipogenic pathway in the ventromedial nucleus of the
      hypothalamus (VMH) prevents CNS-mediated activation of BAT by thyroid hormone and
      reverses the weight loss associated with hyperthyroidism. Similarly, inhibition
      of thyroid hormone receptors in the VMH reverses the weight loss associated with
      hyperthyroidism. This regulatory mechanism depends on AMPK inactivation, as
      genetic inhibition of this enzyme in the VMH of euthyroid rats induces feeding
      independent weight loss and increases expression of thermogenic markers in BAT.
      These effects are reversed by pharmacological blockade of the SNS. Thus, thyroid
      hormone-induced modulation of AMPK activity and lipid metabolism in the
      hypothalamus is a major regulator of whole-body energy homeostasis.

PMID- 20802502
TI  - Apoptosis and DNA damage in human spermatozoa.
AB  - DNA damage is frequently encountered in spermatozoa of subfertile males and is
      correlated with a range of adverse clinical outcomes including impaired
      fertilization, disrupted preimplantation embryonic development, increased rates
      of miscarriage and an enhanced risk of disease in the progeny. The etiology of
      DNA fragmentation in human spermatozoa is closely correlated with the appearance
      of oxidative base adducts and evidence of impaired spermiogenesis. We hypothesize
      that oxidative stress impedes spermiogenesis, resulting in the generation of
      spermatozoa with poorly remodelled chromatin. These defective cells have a
      tendency to default to an apoptotic pathway associated with motility loss,
      caspase activation, phosphatidylserine exteriorization and the activation of free
      radical generation by the mitochondria. The latter induces lipid peroxidation and
      oxidative DNA damage, which then leads to DNA fragmentation and cell death. The
      physical architecture of spermatozoa prevents any nucleases activated as a result
      of this apoptotic process from gaining access to the nuclear DNA and inducing its
      fragmentation. It is for this reason that a majority of the DNA damage
      encountered in human spermatozoa seems to be oxidative. Given the important role
      that oxidative stress seems to have in the etiology of DNA damage, there should
      be an important role for antioxidants in the treatment of this condition. If
      oxidative DNA damage in spermatozoa is providing a sensitive readout of systemic
      oxidative stress, the implications of these findings could stretch beyond our
      immediate goal of trying to minimize DNA damage in spermatozoa as a prelude to
      assisted conception therapy.

PMID- 20802500
TI  - Clinical microfluidics for neutrophil genomics and proteomics.
AB  - Neutrophils have key roles in modulating the immune response. We present a robust
      methodology for rapidly isolating neutrophils directly from whole blood with 'on
      chip' processing for mRNA and protein isolation for genomics and proteomics. We
      validate this device with an ex vivo stimulation experiment and by comparison
      with standard bulk isolation methodologies. Last, we implement this tool as part
      of a near-patient blood processing system within a multi-center clinical study of
      the immune response to severe trauma and burn injury. The preliminary results
      from a small cohort of subjects in our study and healthy controls show a unique
      time-dependent gene expression pattern clearly demonstrating the ability of this
      tool to discriminate temporal transcriptional events of neutrophils within a
      clinical setting.

PMID- 20802504
TI  - Dynamic expression of proteins associated with adventitial remodeling in
      adventitial fibroblasts from spontaneously hypertensive rats.
AB  - AIM: To identify proteins that could potentially be involved in adventitial
      remodeling in vascular adventitial fibroblasts (AFs) from spontaneously
      hypertensive rats (SHR). METHODS: AFs were isolated from thoracic aortas of 4-, 8
      , 16-, and 24-week-old male SHR and Wistar-Kyoto (WKY) rats and cultured to
      passage 4. Proteomic differential expression profiles between SHR-AFs and WKY-AFs
      were investigated using 2-D electrophoresis (2-DE), whereas gel image analysis
      was processed using Image Master 2D Platinum. Protein spots were identified using
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS). Expression levels of annexin A1 in AFs and aortas from SHR and
      WKY rats were detected with Western blotting and immunofluorescence techniques.
      RESULTS: In 4-, 8-, 16-, and 24-week-old SHR-AFs, 49, 59, 54, and 69 protein
      spots were found to have significant differences from the age-matched WKY-AFs.
      Fourteen spots with the same changes in patterns were analyzed in 4-, 8-, 16-,
      and 24-week-old SHR-AFs with mass spectrometry. Except for cytoskeleton proteins
      such as tubulin beta 5, it was found that annexin A1, translation elongation
      factor Tu, endoplasmic reticulum protein 29 and calcium-binding protein 1 were
      expressed in vascular AFs and their levels changed significantly in SHR-AFs
      compared with those in WKY-AFs. A decrease in annexin A1 in SHR-AFs was confirmed
      with Western blotting and immunofluorescence staining at the cell and tissue
      levels. CONCLUSION: The application of proteomic techniques revealed a number of
      novel proteins involved in adventitial remodeling of AFs from SHR, which provide
      new mechanisms responsible for the occurrence and development of hypertension and
      potential targets for influencing vascular remodeling in hypertension.

PMID- 20802503
TI  - Adiponectin resistance and vascular dysfunction in the hyperlipidemic state.
AB  - Insulin plays an important role in the stimulation of vascular nitric oxide
      production, with both short term (vasomotility and anti-thrombotic effects) and
      long term (smooth muscle cell growth and migration inhibition) benefits. Impaired
      vasodilatory response to insulin, the hallmark of vascular insulin resistance
      (IR), has important implications for circulatory pathophysiology. An association
      between adipokines and IR has been observed in both diabetic and nondiabetic
      states. Adiponectin (APN) is an insulin-sensitizing adipokine known to stimulate
      skeletal muscle fatty acid (FA) oxidation and reduce lipid accumulation. Recent
      demonstrations of potential cross-talk between APN and insulin in vascular
      function regulation are particularly interesting. The lipid accumulation observed
      after chronic high-fat (HF) diets and in the obese state may reduce vascular
      response to APN, a pathologic state termed as APN resistance. This review
      highlights the importance of insulin sensitivity and APN activity in the
      maintenance of endothelial function. It explores the relationships between
      vascular IR and APN resistance in the hyperlipidemic pathological condition,
      representative of the metabolic syndrome. The investigation of vascular insulin
      and APN resistance provides not only better understanding of vascular
      pathophysiology, but also an opportunity for therapeutic targeting in individuals
      affected by the metabolic syndrome.

PMID- 20802506
TI  - Different biomechanical properties of medial and adventitial layers of thoracic
      aorta in Wistar-Kyoto and spontaneously hypertensive rats.
AB  - AIM: To evaluate the biomechanical properties of thoracic aorta with or without
      adventitia, and to determine whether there are corresponding changes with
      hypertension. METHODS: Normotensive Wistar-Kyoto (WKY) rats and spontaneously
      hypertensive rats (SHR) at the age of 16 and 32 weeks were used. Thoracic aortic
      adventitial layer was mechanically separated from thoracic aorta and the
      adventitia-denuded artery ring was viewed as thoracic media. A load-strain curve
      was obtained by stretching the ring-shaped intact thoracic aorta or thoracic
      media with a tensile testing machine. Then, the slope of the load-stain curve at
      30%-40% strains was viewed as the elastic stiffness at physiological load,
      whereas the slope near the breaking point was calculated as maximum stiffness.
      The maximum load is the load at the breaking point. RESULTS: There was no
      significant difference in elastic stiffness and maximum stiffness of intact
      thoracic aorta between SHR and age-matched WKY. The elastic stiffness of intact
      thoracic aorta showed no significant difference from that of thoracic media in
      WKY and SHR at both ages. In contrast, both maximum stiffness and maximum load
      were reduced in thoracic media compared with intact thoracic aorta in SHR and WKY
      at both ages. CONCLUSION: These results indicated that vascular adventitia
      contributes to maximum stiffness, but not elastic stiffness in both SHR and WKY.

PMID- 20802505
TI  - Arterial stiffness: a brief review.
AB  - Physical stiffening of the large arteries is the central paradigm of vascular
      aging. Indeed, stiffening in the larger central arterial system, such as the
      aortic tree, significantly contributes to cardiovascular diseases in older
      individuals and is positively associated with systolic hypertension, coronary
      artery disease, stroke, heart failure and atrial fibrillation, which are the
      leading causes of mortality in the developed countries and also in the developing
      world as estimated in 2010 by World Health Organizations. Thus, better, less
      invasive and more accurate measures of arterial stiffness have been developed,
      which prove useful as diagnostic indices, pathophysiological markers and
      predictive indicators of disease. This article presents a review of the
      structural determinants of vascular stiffening, its pathophysiologic determinants
      and its implications for vascular research and medicine. A critical discussion of
      new techniques for assessing vascular stiffness is also presented.

PMID- 20802508
TI  - Regional anesthesia for external cephalic version: its time has come.

PMID- 20802509
TI  - Epoprostenol treatment for idiopathic pulmonary arterial hypertension in
      pregnancy.
AB  - Idiopathic pulmonary arterial hypertension is a rare condition associated with
      significant maternal mortality. We report the management of a 37-year-old
      multigravida with severe disease using epoprostenol, a multidisciplinary
      approach, and a planned delivery. Although the patient survived the pregnancy,
      her pulmonary function significantly worsened. Epoprostenol, a pulmonary
      vasodilator, should be considered when indicated during pregnancy. Neither fetal
      nor neonatal harm was identified.

PMID- 20802507
TI  - Adrenomedullin up-regulates osteopontin and attenuates vascular calcification via
      the cAMP/PKA signaling pathway.
AB  - AIM: To determine whether adrenomedullin (ADM) attenuates vascular calcification
      (VC) by inducing osteopontin (OPN) expression. METHODS: A VC model of rat aorta
      was induced with vitamin D3 plus nicotine (VDN), and vascular smooth muscle cell
      (VSMC) calcification was induced with beta-glycerophosphate. Von Kossa staining
      and alizarin red staining were assessed. Alkaline phosphatase (ALP) activity was
      measured. Immunohistochemical analysis was used to detect alpha-actin, while RT
      PCR and Western blot analysis were used to quantify OPN expression. RESULTS:
      Administration of ADM greatly reduced VC in VDN-treated aortas compared with
      controls, which was confirmed in calcified VSMCs. The decrease in alpha-actin
      expression was ameliorated by ADM both in vivo and in vitro. Moreover, mRNA and
      protein expression levels of OPN were significantly up-regulated in calcified
      aortas, and ADM increased OPN expression in calcified aortas. Furthermore, ADM up
      regulated OPN expression in normal aortas and VSMCs. The ADM-mediated effects
      were similar to that of forskolin, which activates adenylyl cyclase;
      additionally, while the PKA inhibitor H89 and Ca2(+) chelator Fura-2 blocked the
      effect of ADM. However, the MEK/ERK inhibitor PD98509 had no effect on ADM
      induction of OPN mRNA expression. An OPN polyclonal antibody inhibited ADM
      mediated attenuation of VC. CONCLUSION: ADM up-regulates OPN expression and thus
      attenuates VC via PKA. ADM appears to be an endogenous cardiovascular protective
      peptide and may represent a new therapeutic target for VC treatment.

PMID- 20802511
TI  - Essential roles of Jab1 in cell survival, spontaneous DNA damage and DNA repair.
AB  - Jun activation domain-binding protein 1 (JAB1) is a multifunctional protein that
      participates in the control of cell proliferation and the stability of multiple
      proteins. JAB1 overexpression has been implicated in the pathogenesis of human
      cancer. JAB1 regulates several key proteins and thereby produces varied effects
      on cell cycle progression, genome stability and cell survival. However, the
      biological significance of JAB1 activity in these cellular signaling pathways is
      unclear. Therefore, we developed mice that were deficient in Jab1 and analyzed
      the null embryos and heterozygous cells. This disruption of Jab1 in mice resulted
      in early embryonic lethality due to accelerated apoptosis. Loss of Jab1
      expression sensitized both mouse primary embryonic fibroblasts and osteosarcoma
      cells to gamma-radiation-induced apoptosis, with an increase in spontaneous DNA
      damage and homologous recombination (HR) defects, both of which correlated with
      reduced levels of the DNA repair protein Rad51 and elevated levels of p53.
      Furthermore, the accumulated p53 directly binds to Rad51 promoter, inhibits its
      activity and represents a major mechanism underlying the HR repair defect in Jab1
      deficient cells. These results indicate that Jab1 is essential for efficient DNA
      repair and mechanistically link Jab1 to the maintenance of genome integrity and
      to cell survival.

PMID- 20802512
TI  - The expression of activated Y-box binding protein-1 serine 102 mediates
      trastuzumab resistance in breast cancer cells by increasing CD44+ cells.
AB  - The development of acquired resistance to trastuzumab remains a prevalent
      challenge in the treatment of patients whose tumors express human epidermal
      growth factor 2 (HER2). We previously reported that HER2 overexpressing breast
      cancers are dependent on Y-box binding protein-1 (YB-1) for growth and survival.
      As YB-1 is also linked to drug resistance in other types of cancer, we address
      its possible role in trastuzumab insensitivity. Employing an in vivo model of
      acquired resistance, we demonstrate that resistant cell lines have elevated
      levels of P-YB-1(S102) and its activating kinase P-RSK and these levels are
      sustained following trastuzumab treatment. Further, to demonstrate the importance
      of YB-1 in mediating drug resistance, the expression of the active mutant YB
      1(S102D) rendered the BT474 cell line insensitive to trastuzumab. Questioning the
      role of tumor-initiating cells (TIC) and their ability to escape cancer
      therapies, we investigate YB-1's role in inducing the cancer stem cell marker
      CD44. Notably, the resistant cells express more CD44 mRNA and protein compared
      with BT474 cells, which correlated with increased mammosphere formation.
      Expression of YB-1(S102D) in the BT474 cells increase CD44 protein levels,
      resulting in enhanced mammosphere formation. Further, exposing BT474 cells to
      trastuzumab selected for a resistant sub-population enriched for CD44.
      Conversely, small intefering RNA inhibition of CD44 restored trastuzumab
      sensitivity in the resistant cell lines. Our findings provide insight on a novel
      mechanism employed by tumor cells to acquire the ability to escape the effects of
      trastuzumab and suggest that targeting YB-1 may overcome resistance by
      eliminating the unresponsive TIC population, rendering the cancer sensitive to
      therapy.

PMID- 20802513
TI  - Phosphorylation of focal adhesion kinase on tyrosine 194 by Met leads to its
      activation through relief of autoinhibition.
AB  - Focal adhesion kinase (FAK) has a crucial role in integration of signals from
      integrins and growth factor receptors. In this study, we demonstrate that growth
      factor receptors including hepatocyte growth factor receptor Met, epidermal
      growth factor receptor, and platelet-derived growth factor receptor directly
      phosphorylate FAK on Tyr194 in the FERM domain (band 4.1 and ezrin/radixin/moesin
      homology domain). Upon binding to Met or phosphoinositides, FAK may undergo
      conformational changes, which renders Tyr194 accessible for phosphorylation.
      Substitution of Tyr194 with Phe significantly suppresses the activation of FAK by
      Met. In contrast, substitution of Tyr194 with Glu (Y194E substitution) leads to
      constitutive activation of FAK. The phosphorylation of FAK on Tyr194 may cause
      conformational changes in the FERM domain, which disrupts the intramolecular
      inhibitory interaction between the FERM and kinase domains of FAK. Moreover,
      substitution of the basic residues in the (216)KAKTLRK(222) patch in the FERM
      domain with Ala antagonizes the effect of the Y194E substitution on FAK
      activation, thus suggesting that the interactions between the phosphorylated
      Tyr194 and the basic resides in the (216)KAKTLRK(222) patch may allow FAK to be
      activated through relief of its autoinhibition. Collectively, this study provides
      the first example to explain how FAK is activated by receptor tyrosine kinases.

PMID- 20802514
TI  - The role of fibroblast Tiam1 in tumor cell invasion and metastasis.
AB  - The co-evolution of tumors and their microenvironment involves bidirectional
      communication between tumor cells and tumor-associated stroma. Various cell types
      are present in tumor-associated stroma, of which fibroblasts are the most
      abundant. The Rac exchange factor Tiam1 is implicated in multiple signaling
      pathways in epithelial tumor cells and lack of Tiam1 in tumor cells retards tumor
      growth in Tiam1 knockout mouse models. Conversely, tumors arising in Tiam1
      knockout mice have increased invasiveness. We have investigated the role of Tiam1
      in tumor-associated fibroblasts as a modulator of tumor cell invasion and
      metastasis, using retroviral delivery of short hairpin RNA to suppress Tiam1
      levels in three different experimental models. In spheroid co-culture of mammary
      epithelial cells and fibroblasts, Tiam1 silencing in fibroblasts led to increased
      epithelial cell outgrowth into matrix. In tissue-engineered human skin, Tiam1
      silencing in dermal fibroblasts led to increased invasiveness of epidermal
      keratinocytes with pre-malignant features. In a model of human breast cancer in
      mice, co-implantation of mammary fibroblasts inhibited tumor invasion and
      metastasis, which was reversed by Tiam1 silencing in co-injected fibroblasts.
      These results suggest that stromal Tiam1 may have a role in modulating the
      effects of the tumor microenvironment on malignant cell invasion and metastasis.
      This suggests a set of pathways for further investigation, with implications for
      future therapeutic targets.

PMID- 20802515
TI  - Inhibition of beta1 integrin and IL-3Rbeta common subunit interaction hinders
      tumour angiogenesis.
AB  - Integrin/cytokine receptor interaction provides permissive signals leading to
      neoangiogenesis, and integrins are crucial for differentiation of endothelial
      progenitor cells (EPCs). It is known that the inflammatory interleukin-3 (IL-3),
      released in the tumoral microenvironment, contributes to both angiogenesis and
      vasculogenic processes. Herein, we generated IL-3 receptor beta common (IL
      3Rbetac) extracellular domain-derived fusion proteins (Fc) to elucidate the
      molecular mechanisms regulating these processes. Three different Fc were
      generated, containing the entire extracellular domain of IL-3Rbetac (Fc1.4), a
      fragment corresponding to domains 1-3 (Fc1.3) and a fragment corresponding to
      domain 4 (Fc4), respectively. The ability of the fusion proteins to interfere
      with IL-3Rbetac/beta1 integrin interaction was assessed on endothelial cells
      (ECs), EPCs and murine-derived ECs. Pull-down experiments showed that Fc1.4 and
      Fc4 fusion proteins specifically interacted with beta1 integrin. Fc4 and Fc1.4
      fragments prevented IL-3-mediated EPC expansion, arterial morphogenesis and
      tumour-derived EC migration, without affecting cell adhesion. Fc4 in vivo
      inhibited the IL-3-mediated vasculogenic process, as well as inflammatory and
      tumour vascular growth. In conclusion, these data identify the beta1 integrin
      interacting domain in the juxta-membrane IL-3Rbetac extracellular domain, and
      provide the rational for targeting this interaction to impair vascular growth.

PMID- 20802516
TI  - PARP1 is activated at telomeres upon G4 stabilization: possible target for
      telomere-based therapy.
AB  - New anti-telomere strategies represent important goals for the development of
      selective cancer therapies. In this study, we reported that uncapped telomeres,
      resulting from pharmacological stabilization of quadruplex DNA by RHPS4 (3,11
      difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate), trigger
      specific recruitment and activation of poly-adenosine diphosphate (ADP) ribose
      polymerase I (PARP1) at the telomeres, forming several ADP-ribose polymers that
      co-localize with the telomeric repeat binding factor 1 protein and are inhibited
      by selective PARP(s) inhibitors or PARP1-specific small interfering RNAs. The
      knockdown of PARP1 prevents repairing of RHPS4-induced telomere DNA breaks,
      leading to increases in chromosome abnormalities and eventually to the inhibition
      of tumor cell growth both in vitro and in xenografts. More interestingly, the
      integration of a TOPO1 inhibitor on the combination treatment proved to have a
      high therapeutic efficacy ensuing a complete regression of the tumor as well as a
      significant increase in overall survival and cure of mice even when treatments
      started at a very late stage of tumor growth. Overall, this work reveals the
      unexplored link between the PARP1 and G-quadruplex ligands and demonstrates the
      excellent efficacy of a multi-component strategy based on the use of PARP
      inhibitors in telomere-based therapy.

PMID- 20802518
TI  - Exogenous cell-permeable C6 ceramide sensitizes multiple cancer cell lines to
      Doxorubicin-induced apoptosis by promoting AMPK activation and mTORC1 inhibition.
AB  - New chemotherapy-enhancing strategies are needed for better cancer therapy.
      Previous studies suggest that exogenous cell-permeable C6 ceramide may be a
      useful adjunct to the anti-tumor effects of chemotherapeutic agents (such as
      Taxol) against multiple cancers. Here we demonstrate that exogenous cell
      permeable C6 ceramide largely sensitizes multiple progressive cancer cell lines
      to Doxorubicin-induced cell death and apoptosis. We found for the first time that
      Doxorubicin induces AMP-activated protein kinase (AMPK) activation in a reactive
      oxygen species-dependent manner. Activation of AMPK contributes to Doxorubicin
      induced cancer cell death and apoptosis. Inhibition of AMPK by small interfering
      RNA knockdown or a pharmacological inhibitor reduces Doxorubicin-induced cancer
      cell apoptosis, whereas AMPK activator AICAR enhances it. Importantly, we found
      that C6 ceramide largely enhances Doxorubicin-induced activation of AMPK, which
      leads to mTOR complex 1 inhibition and chemo-sensitization. Our data suggest that
      the combination of C6 ceramide with traditional chemotherapy drugs such as
      Doxorubicin may have the potential to be used as a new therapeutic intervention
      against multiple cancers.

PMID- 20802517
TI  - DNA copy number aberrations in small-cell lung cancer reveal activation of the
      focal adhesion pathway.
AB  - Small-cell lung cancer (SCLC) is the most aggressive subtype of lung cancer in
      its clinical behavior, with a 5-year overall survival as low as 5%. Despite years
      of research in the field, molecular determinants of SCLC behavior are still
      poorly understood, and this deficiency has translated into an absence of specific
      diagnostics and targeted therapeutics. We hypothesized that tumor DNA copy number
      alterations would allow the identification of molecular pathways involved in SCLC
      progression. Array comparative genomic hybridization was performed on DNA
      extracted from 46 formalin-fixed paraffin-embedded SCLC tissue specimens. Genomic
      profiling of tumor and sex-matched control DNA allowed the identification of 70
      regions of copy number gain and 55 regions of copy number loss. Using molecular
      pathway analysis, we found a strong enrichment in these regions of copy number
      alterations for 11 genes associated with the focal adhesion pathway. We verified
      these findings at the genomic, gene expression and protein level. Focal Adhesion
      Kinase (FAK), one of the central genes represented in this pathway, was commonly
      expressed in SCLC tumors and constitutively phosphorylated in SCLC cell lines.
      Those were poorly adherent to most substrates but not to laminin-322. Inhibition
      of FAK phosphorylation at Tyr(397) by a small-molecule inhibitor, PF-573,228,
      induced a dose-dependent decrease of adhesion and an increase of spreading in
      SCLC cell lines on laminin-322. Cells that tended to spread also showed a
      decrease in focal adhesions, as demonstrated by a decreased vinculin expression.
      These results support the concept that pathway analysis of genes in regions of
      copy number alterations may uncover molecular mechanisms of disease progression
      and demonstrate a new role of FAK and associated adhesion pathways in SCLC.
      Further investigations of FAK at the functional level may lead to a better
      understanding of SCLC progression and may have therapeutic implications.

PMID- 20802519
TI  - Mammary-derived growth inhibitor (MDGI) interacts with integrin alpha-subunits
      and suppresses integrin activity and invasion.
AB  - The majority of mortality associated with cancer is due to formation of
      metastases from the primary tumor. Adhesion mediated by different integrin
      heterodimers has an important role during cell migration and invasion. Protein
      interactions with the beta1-integrin cytoplasmic tail are known to influence
      integrin affinity for extracellular ligands, but regulating binding partners for
      the alpha-subunit cytoplasmic tails have remained elusive. In this study, we show
      that mammary-derived growth inhibitor (MDGI) (also known as FABP-3 or H-FABP)
      binds directly to the cytoplasmic tail of integrin alpha-subunits and its
      expression inhibits integrin activity. In breast cancer cell lines, MDGI
      expression correlates with suppression of the active conformation of integrins.
      This results in reduced integrin adhesion to type I collagen and fibronectin and
      inhibition of cell migration and invasion. In tissue microarray of 1331 breast
      cancer patients, patients with MDGI-positive tumors had more favorable 10-year
      distant disease-free survival compared with patients with MDGI-negative tumors.
      Our data indicate that MDGI is a novel interacting partner for integrin alpha
      subunits, and its expression modulates integrin activity and suppresses cell
      invasion in breast cancer patients. Retained MDGI expression is associated with
      favorable prognosis.

PMID- 20802520
TI  - Dissection of mitogenic and neurodegenerative actions of cystine and glutamate in
      malignant gliomas.
AB  - Malignant glioma represents one of the most aggressive and lethal human
      neoplasias. A hallmark of gliomas is their rapid proliferation and destruction of
      vital brain tissue, a process in which excessive glutamate release by glioma
      cells takes center stage. Pharmacologic antagonism with glutamate signaling
      through ionotropic glutamate receptors attenuates glioma progression in vivo,
      indicating that glutamate release by glioma cells is a prerequisite for rapid
      glioma growth. Glutamate has been suggested to promote glioma cell proliferation
      in an autocrine or paracrine manner, in particular by activation of the (RS)
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrate (AMPA) subtype
      of glutamate receptors. Here, we dissect the effects of glutamate secretion on
      glioma progression. Glioma cells release glutamate through the amino-acid
      antiporter system X(c)(-), a process that is mechanistically linked with cystine
      incorporation. We show that disrupting glutamate secretion by interfering with
      the system X(c)(-) activity attenuates glioma cell proliferation solely cystine
      dependently, whereas glutamate itself does not augment glioma cell growth in
      vitro. Neither AMPA receptor agonism nor antagonism affects glioma growth in
      vitro. On a molecular level, AMPA insensitivity is concordant with a pronounced
      transcriptional downregulation of AMPA receptor subunits or overexpression of the
      fully edited GluR2 subunit, both of which block receptor activity. Strikingly,
      AMPA receptor inhibition in tumor-implanted brain slices resulted in markedly
      reduced tumor progression associated with alleviated neuronal cell death,
      suggesting that the ability of glutamate to promote glioma progression strictly
      requires the tumor microenvironment. Concerning a potential pharmacotherapy,
      targeting system X(c)(-) activity disrupts two major pathophysiological
      properties of glioma cells, that is, the induction of excitotoxic neuronal cell
      death and incorporation of cystine required for rapid proliferation.

PMID- 20802521
TI  - ERK and JNK activation is essential for oncogenic transformation by v-Rel.
AB  - v-Rel is the acutely oncogenic member of the NF-kappaB family of transcription
      factors. Infection with retroviruses expressing v-Rel rapidly induces fatal
      lymphomas in birds and transforms primary lymphocytes and fibroblasts in vitro.
      We have previously shown that AP-1 transcriptional activity contributes to v-Rel
      mediated transformation. Although v-Rel increases the expression of these
      factors, their activity may also be induced through phosphorylation by the
      mitogen-activated protein kinases (MAPKs). The expression of v-Rel results in the
      strong and sustained activation of the ERK and JNK MAPK pathways. This induction
      is critical for the v-Rel-transformed phenotype, as suppression of MAPK activity
      with chemical inhibitors or small interfering RNA severely impairs colony
      formation of v-Rel-transformed lymphoid cell lines. However, signaling must be
      maintained within an optimal range in these cells, as strong additional
      activation of either pathway beyond the levels induced by v-Rel through the
      expression of constitutively active MAPK proteins attenuates the transformed
      phenotype. MAPK signaling also has an important role in the initial
      transformation of primary spleen cells by v-Rel, although distinct requirements
      for MAPK activity at different stages of v-Rel-mediated transformation were
      identified. We also show that the ability of v-Rel to induce MAPK signaling more
      strongly than c-Rel contributes to its greater oncogenicity.

PMID- 20802522
TI  - A functional SUMO-interacting motif in the transactivation domain of c-Myb
      regulates its myeloid transforming ability.
AB  - c-Myb is an essential hematopoietic transcription factor that controls
      proliferation and differentiation of progenitors during blood cell development.
      Whereas sumoylation of the C-terminal regulatory domain (CRD) is known to have a
      major impact on the activity of c-Myb, no role for noncovalent binding of small
      ubiquitin-like modifier (SUMO) to c-Myb has been described. Based on the
      consensus SUMO-interacting motif (SIM), we identified and examined putative SIMs
      in human c-Myb. Interaction and reporter assays showed that the SIM in the in the
      transactivation domain of c-Myb (V(267)NIV) is functional. This motif is
      necessary for c-Myb to be able to interact noncovalently with SUMO,
      preferentially SUMO2/3. Destroying the SUMO-binding properties by mutation
      resulted in a large increase in the transactivation potential of c-Myb.
      Mutational analysis and overexpression of conjugation-defective SUMO argued
      against intramolecular repression caused by sumoylated CRD and in favor of SUMO
      dependent repression in trans. Using both a myeloid cell line-based assay and a
      primary hematopoietic cell assay, we addressed the transforming abilities of SUMO
      binding and conjugation mutants. Interestingly, only loss of SUMO binding, and
      not SUMO conjugation, enhanced the myeloid transformational potential of c-Myb. c
      Myb with the SIM mutated conferred a higher proliferative ability than the wild
      type and caused an effective differentiation block. This establishes SUMO binding
      as a mechanism involved in modulating the transactivation activity of c-Myb, and
      responsible for keeping the transforming potential of the oncoprotein in check.

PMID- 20802523
TI  - Transforming growth factor-beta-induced epithelial-mesenchymal transition
      facilitates epidermal growth factor-dependent breast cancer progression.
AB  - Transforming growth factor-beta (TGF-beta) and epidermal growth factor (EGF) have
      critical roles in regulating the metastasis of aggressive breast cancers, yet the
      impact of epithelial-mesenchymal transition (EMT) induced by TGF-beta in altering
      the response of breast cancer cells to EGF remains unknown. We show in this study
      that murine metastatic 4T1 breast cancer cells formed compact and dense spheroids
      when cultured under three-dimensional (3D) conditions, which was in sharp
      contrast to the branching phenotypes exhibited by their nonmetastatic
      counterparts. Using the human MCF10A series, we show that epithelial-type and
      nonmetastatic breast cancer cells were unable to invade to EGF, whereas their
      mesenchymal-type and metastatic counterparts readily invaded to EGF. Furthermore,
      EMT induced by TGF-beta was sufficient to manifest dense spheroid morphologies, a
      phenotype that increased primary tumor exit and invasion to EGF. Post-EMT
      invasion to EGF was dependent on increased activation of EGF receptor (EGFR) and
      p38 mitogen-activated protein kinase, all of which could be abrogated either by
      pharmacologic (PF-562271) or by genetic (shRNA) targeting of focal adhesion
      kinase (FAK). Mechanistically, EMT induced by TGF-beta increased cell-surface
      levels of EGFR and prevented its physical interaction with E-cadherin, leading
      instead to the formation of oncogenic signaling complexes with TbetaR-II.
      Elevated EGFR expression was sufficient to transform normal mammary epithelial
      cells, and to progress their 3D morphology from that of hollow acini to branched
      structures characteristic of nonmetastatic breast cancer cells. Importantly, we
      show that TGF-beta stimulation of EMT enabled this EGFR-driven breast cancer
      model to abandon their inherent branching architecture and form large,
      undifferentiated masses that were hyperinvasive to EGF and showed increased
      pulmonary tumor growth upon tail vein injection. Finally, chemotherapeutic
      targeting of FAK was sufficient to revert the aggressive behaviors of these
      structures. Collectively, this investigation has identified a novel EMT-based
      approach to neutralize the oncogenic activities of EGF and TGF-beta in aggressive
      and invasive forms of breast cancer.

PMID- 20802524
TI  - Epigenetic inactivation of T-box transcription factor 5, a novel tumor suppressor
      gene, is associated with colon cancer.
AB  - T-box transcription factor 5 (TBX5) is a member of a phylogenetically conserved
      family of genes involved in the regulation of developmental processes. The
      function of TBX5 in cancer development is largely unclear. We identified that
      TBX5 was preferentially methylated in cancer using methylation-sensitive
      arbitrarily primed PCR. We aim to clarify the epigenetic inactivation, biological
      function and clinical significance of TBX5 in colon cancer. Promoter methylation
      was evaluated by combined bisulfite restriction analysis and bisulfite genomic
      sequencing. Cell proliferation was examined by cell viability assay and colony
      formation assay, apoptosis by flow cytometry and cell migration by wound-healing
      assay. TBX5 target genes were identified by cDNA microarray analysis. Cox
      regression model and log-rank test were used to identify independent predictors
      of prognosis. TBX5 was silenced or downregulated in 88% (7/8) colon cancer cell
      lines, but was expressed in normal colon tissues. Loss of gene expression was
      associated with promoter methylation. The biological function of TBX5 in human
      colon cancer cells was examined. Re-expression of TBX5 in silenced colon cancer
      cell lines suppressed colony formation (P<0.001), proliferation (P<0.001),
      migration and induced apoptosis (P<0.01). Induction of apoptosis was mediated
      through cross-talk of extrinsic apoptosis pathway, apoptotic BCL2-associated X
      protein and Granzyme A signaling cascades. TBX5 suppressed tumor cell
      proliferation and metastasis through the upregulation of cyclin-dependent kinase
      inhibitor 2A, metastasis suppressor 1 and downregulation of synuclein gamma and
      metastasis-associated protein 1 family member 2. TBX5 methylation was detected in
      68% (71/105) of primary colon tumors. Multivariate analysis showed that patients
      with TBX5 methylation had a significantly poor overall survival (P=0.0007). In
      conclusion, we identified a novel functional tumor suppressor gene TBX5
      inactivated by promoter methylation in colon cancer. Detection of methylated TBX5
      may serve as a potential biomarker for the prognosis of this malignancy.

PMID- 20802525
TI  - CpG island hypermethylation-associated silencing of non-coding RNAs transcribed
      from ultraconserved regions in human cancer.
AB  - Although only 1.5% of the human genome appears to code for proteins, much effort
      in cancer research has been devoted to this minimal fraction of our DNA. However,
      the last few years have witnessed the realization that a large class of non
      coding RNAs (ncRNAs), named microRNAs, contribute to cancer development and
      progression by acting as oncogenes or tumor suppressor genes. Recent studies have
      also shown that epigenetic silencing of microRNAs with tumor suppressor features
      by CpG island hypermethylation is a common hallmark of human tumors. Thus, we
      wondered whether there were other ncRNAs undergoing aberrant DNA methylation
      associated silencing in transformed cells. We focused on the transcribed
      ultraconserved regions (T-UCRs), a subset of DNA sequences that are absolutely
      conserved between orthologous regions of the human, rat and mouse genomes and
      that are located in both intra- and intergenic regions. We used a pharmacological
      and genomic approach to reveal the possible existence of an aberrant epigenetic
      silencing pattern of T-UCRs by treating cancer cells with a DNA-demethylating
      agent followed by hybridization to an expression microarray containing these
      sequences. We observed that DNA hypomethylation induces release of T-UCR
      silencing in cancer cells. Among the T-UCRs that were reactivated upon drug
      treatment, Uc.160+, Uc283+A and Uc.346+ were found to undergo specific CpG island
      hypermethylation-associated silencing in cancer cells compared with normal
      tissues. The analysis of a large set of primary human tumors (n=283) demonstrated
      that hypermethylation of the described T-UCR CpG islands was a common event among
      the various tumor types. Our finding that, in addition to microRNAs, another
      class of ncRNAs (T-UCRs) undergoes DNA methylation-associated inactivation in
      transformed cells supports a model in which epigenetic and genetic alterations in
      coding and non-coding sequences cooperate in human tumorigenesis.

PMID- 20802526
TI  - K-Ras4B phosphorylation at Ser181 is inhibited by calmodulin and modulates K-Ras
      activity and function.
AB  - Fine tuning of Ras activity is widely known as a mechanism to induce different
      cellular responses. Recently, we have shown that calmodulin (CaM) binds to K-Ras
      and that K-Ras phosphorylation inhibits its interaction with CaM. In this study
      we report that CaM inhibits K-Ras phosphorylation at Ser181 by protein kinase C
      (PKC) in vivo, and this is a mechanism to modulate K-Ras activity and signaling.
      Although CaM inhibition increased the activation of endogenous K-Ras, PKC
      inhibition decreased its activation status. We demonstrate that K-Ras
      phosphorylation decreased susceptibility to p120GAP activity. Accordingly, we
      also observed that non-phosphorylable K-Ras mutant exhibits a less sustained
      activation profile and do not efficiently activate AKT at low growth factor doses
      compared with wild-type K-Ras. It is interesting that the physiological responses
      induced by K-Ras are affected by this phosphorylation; when K-Ras cannot be
      phosphorylated it exhibits a remarkably decreased ability to stimulate
      proliferation in non-saturated serum conditions. Finally, we demonstrate that
      phosphorylation also regulates oncogenic K-Ras functions, as focus formation
      capacity, mobility and apoptosis resistance upon adriamycin treatment of cells
      expressing oncogenic K-Ras that cannot be phosphorylated are highly compromised.
      Moreover, at low serum concentration proliferation and survival is practically
      inhibited when cells cannot phosphorylate oncogenic K-Ras. In this condition, K
      Ras phosphorylation is essential to ensure a proper activation of mitogen
      activated protein kinase and PI3K/AKT pathways. In summary, our findings suggest
      that the interplay between CaM interaction and PKC phosphorylation is essential
      to regulate non-oncogenic and oncogenic K-Ras activity and functionality.

PMID- 20802528
TI  - A novel concept in antiangiogenic and antitumoral therapy: multitarget
      destabilization of short-lived mRNAs by the zinc finger protein ZFP36L1.
AB  - Angiogenesis inhibitors have shown clinical benefits in patients with advanced
      cancer, but further therapeutic improvement is needed. We have previously shown
      that the zinc finger protein 36, C3H type-like 1 (ZFP36L1) enhances vascular
      endothelial growth factor (VEGF) mRNA decay through its interaction with AU-rich
      elements within VEGF 3'-untranslated region. In this study, we evaluated the
      possibility to develop an antiangiogenic and antitumoral strategy using the mRNA
      destabilizing activity of ZFP36L1. We engineered a cell-penetrating ZFP36L1, by
      fusing it to the protein transduction domains (PTDs) TAT derived from HIV, or the
      polyarginine peptides R7 or R9. PTD-ZFP36L1 fusion proteins were expressed in
      bacterial cells and affinity-purified to homogeneity. TAT-, R7- and R9-ZFP36L1
      were efficiently internalized into living cells and decreased both endogenous
      VEGF mRNA half-life and VEGF protein levels in vitro. Importantly, a single
      injection of R9-TIS11b fusion protein into a high-VEGF expressing tissue in vivo
      (in this study, the mouse adrenal gland) markedly decreased VEGF expression. We
      further evaluated the effect of R9-ZFP36L1 on tumor growth using Lewis Lung
      Carcinoma (LL/2) cells implanted subcutaneously into nude mice. Intratumoral
      injection of R9-ZFP36L1 significantly reduced tumor growth and markedly decreased
      the expression of multiple angiogenic and inflammatory cytokines, including VEGF,
      acidic fibroblast growth factor, tumor necrosis factor alpha, interleukin (IL)
      1alpha and IL-6, with a concomitant obliteration of tumor vascularization. These
      findings indicate that R9-ZFP36L1 fusion protein may represent a novel
      antiangiogenic and antitumoral agent, and supports the emerging idea that
      modulation of mRNA stability represents a promising therapeutic approach to treat
      cancer.

PMID- 20802527
TI  - Pancreatic adenocarcinoma upregulated factor promotes metastasis by regulating
      TLR/CXCR4 activation.
AB  - Pancreatic adenocarcinoma upregulated factor (PAUF) is overproduced in certain
      types of cancer. However, little is known of the tumorigenic function of PAUF. In
      this study, we report the X-ray crystal structure of PAUF and reveal that PAUF is
      a mammalian lectin normally found in plant lectins. We also identify PAUF as an
      endogenous ligand of Toll-like receptor 2 (TLR2) and TLR4 by screening
      extracellular domain receptor pools. We further confirmed the specificity of the
      PAUF-TLR2 interaction. PAUF induces extracellular signal-regulated kinase (ERK)
      phosphorylation and activates the IKK-beta-mediated TPL2/MEK/ERK signaling
      pathway through TLR2. In agreement with the result of TLR2-mediated ERK
      activation by PAUF, PAUF induces increased expression of the protumorigenic
      cytokines RANTES and MIF in THP-1 cells. However, PAUF does not fully activate
      Ikappa-B-alpha signaling pathways in THP-1 cells, and fails to translocate the
      p65 subunit of the nuclear factor-kappaB (NF-kappaB) complex into the nucleus,
      resulting in no NF-kappaB activation. Surprisingly, we found that PAUF also
      associated with the CXC chemokine receptor (CXCR4)-TLR2 complex and inhibited
      CXCR4-dependent, TLR2-mediated NF-kappaB activation. Together, these findings
      suggest that the new cancer-associated ligand, PAUF, may activate TLR-mediated
      ERK signaling to produce the protumorigenic cytokines, but inhibits TLR-mediated
      NF-kappaB signaling, thereby facilitating tumor growth and escape from innate
      immune surveillance.

PMID- 20802529
TI  - An ERK-dependent pathway to Noxa expression regulates apoptosis by platinum-based
      chemotherapeutic drugs.
AB  - Cisplatin is a widely used cancer chemotherapeutic that promotes DNA damage
      associated apoptosis. Although platinum compounds are known to form DNA adducts
      and provoke DNA damage, the molecular mechanism of cisplatin-induced cell death
      remains unclear. In this article, we show that the BH3-only protein Noxa is
      strongly transcriptionally upregulated in response to cisplatin and related
      platinum compounds. Cisplatin-induced Noxa expression was ERK dependent, but p53
      independent, and inhibition of ERK activation markedly attenuated cisplatin
      induced cell death, as well as Noxa expression. Furthermore, siRNA-mediated
      ablation of Noxa expression also inhibited cisplatin-induced cell death and
      permitted clonogenic survival. These observations reveal a novel ERK-regulated
      route to Noxa expression that is important for the cell killing activity of
      platinum-based chemotherapeutic drugs.

PMID- 20802530
TI  - MicroRNA dysregulation in gastric cancer: a new player enters the game.
AB  - Gastric carcinogenesis is a multistep process involving genetic and epigenetic
      alteration of protein-coding proto-oncogenes and tumor-suppressor genes. Recent
      discoveries have shed new light on the involvement of a class of noncoding RNA
      known as microRNA (miRNA) in gastric cancer. A substantial number of miRNAs show
      differential expression in gastric cancer tissues. Genes coding for these miRNAs
      have been characterized as novel proto-oncogenes and tumor-suppressor genes based
      on findings that these miRNAs control malignant phenotypes of gastric cancer
      cells. In this connection, miRNA dysregulation promotes cell-cycle progression,
      confers resistance to apoptosis, and enhances invasiveness and metastasis.
      Moreover, certain polymorphisms in miRNA genes are associated with increased
      risks for atrophic gastritis and gastric cancer, whereas circulating levels of
      miRNAs may serve as biomarkers for early diagnosis. Several miRNAs have also been
      shown to correlate with gastric cancer progression, and thus may be used as
      prognostic markers. Elucidating the biological aspects of miRNA dysregulation may
      help us better understand the pathogenesis of gastric cancer and promote the
      development of miRNA-directed therapeutics against this deadly disease.

PMID- 20802531
TI  - Suppression of cell-cycle progression by Jun dimerization protein-2 (JDP2)
      involves downregulation of cyclin-A2.
AB  - We report here a novel role for Jun dimerization protein-2 (JDP2) as a regulator
      of the progression of normal cells through the cell cycle. To determine the role
      of JDP2 in vivo, we generated Jdp2-knockout (Jdp2KO) mice by targeting exon-1 to
      disrupt the site of initiation of transcription. The epidermal thickening of skin
      from the Jdp2KO mice after treatment with 12-O-tetradecanoylphorbol 13-acetate
      (TPA) proceeded more rapidly than that of control mice, and more proliferating
      cells were found at the epidermis. Fibroblasts derived from embryos of Jdp2KO
      mice proliferated faster and formed more colonies than fibroblasts from wild-type
      mice. JDP2 was recruited to the promoter of the gene for cyclin-A2 (ccna2) at the
      AP-1 site. Cells lacking Jdp2 had elevated levels of cyclin-A2 mRNA. Furthermore,
      reintroduction of JDP2 resulted in the repression of transcription of ccna2 and
      of cell-cycle progression. Thus, transcription of the gene for cyclin-A2 appears
      to be a direct target of JDP2 in the suppression of cell proliferation.

PMID- 20802532
TI  - Hedgehog signaling maintains chemoresistance in myeloid leukemic cells.
AB  - The development of resistance against chemotherapy remains one of the major
      challenges in the clinical management of leukemia. There is still limited insight
      into the molecular mechanisms that maintain the chemotherapy-resistant phenotype,
      despite the obvious clinical relevance that such knowledge would have. In this
      study, we show that the chemotherapy-resistant phenotype of myeloid leukemia
      cells correlates with activation of the Hedgehog (Hh) pathway, whereas in
      chemosensitive cells, such activation is less pronounced. Importantly, the
      overexpression of Hh pathway components induces chemoprotection and inhibition of
      the pathway reverts chemoresistance of Lucena-1 cells, apparently by interfering
      with P-glycoprotein-dependent drug resistance. Our data thus identify the Hh
      pathway as an essential component of multidrug resistance (MDR) myeloid leukemia
      and suggest that targeting the Hh pathway might be an interesting therapeutic
      avenue for overcoming MDR resistance in myeloid leukemia.

PMID- 20802533
TI  - Identification of FUSE-binding protein 1 as a regulatory mRNA-binding protein
      that represses nucleophosmin translation.
AB  - Nucleophosmin (NPM/B23) is a multifunctional oncoprotein whose protein expression
      levels dictate cellular growth and proliferation rates. NPM is translationally
      responsive to hyperactive mammalian target of rapamycin (mTOR) signals, but the
      mechanism of this regulation is not understood. Using chimeric translational
      reporters, we found that the 3' untranslated region (UTR) of the NPM messenger
      (m)RNA is sufficient to mediate its translational modulation by mTOR signalling.
      We show that far upstream element (FUSE)-binding protein 1 (FBP1) interacts
      specifically with the 3' UTR of NPM to repress translation. Overexpression of
      FBP1 resulted in translational repression of NPM mRNAs, whereas depletion of FBP1
      caused a dramatic increase in NPM translation and resulted in enhanced overall
      cell proliferation. Thus, we propose that FBP1 is a key regulator of cell growth
      and proliferation through its ability to selectively bind the NPM 3' UTR and
      repress NPM translation.

PMID- 20802535
TI  - A novel source of tetraploid cancer cell precursors: telomere insufficiency links
      aging to oncogenesis.
AB  - Epithelial cancers of the elderly are caused by a combination of telomere
      dysfunction and the mutational invalidation of major tumor suppressors including
      p53. A recent article published in Cell by Davoli et al. shows that the
      simultaneous elimination of p53 and telomerase causes a state of chronic DNA
      damage that results in tetraploidization through endoreplication, that is, two
      consecutive S phases that are not separated by mitosis. As tetraploid cells
      represent a metastable intermediate between normal diploidy and cancer-associated
      aneuploidy, this novel route to tetraploidization may constitute (one of) the
      functional link(s) between aging and carcinogenesis.

PMID- 20802534
TI  - Hypoxia and cell cycle regulation of the von Hippel-Lindau tumor suppressor.
AB  - Inactivation of von Hippel-Lindau tumor-suppressor protein (pVHL) is associated
      with von Hippel-Lindau disease, an inherited cancer syndrome, as well as the
      majority of patients with sporadic clear cell renal cell carcinoma (RCC).
      Although the involvement of pVHL in oxygen sensing through targeting hypoxia
      inducible factor-alpha subunits to ubiquitin-dependent proteolysis has been well
      documented, less is known about pVHL regulation under both normoxic and hypoxic
      conditions. We found that pVHL levels decreased in hypoxia and that hypoxia
      induced cell cycle arrest is associated with pVHL expression in RCC cells. pVHL
      levels fluctuate during the cell cycle, paralleling cyclin B1 levels, with
      decreased levels in mitosis and G1. pVHL contains consensus destruction (D) box
      sequences, and pVHL associates with Cdh1, an activator of the anaphase-promoting
      complex/cyclosome (APC/C) E3 ubiquitin ligase. We show that pVHL has a decreased
      half-life in G1, Cdh1 downregulation results in increased pVHL expression,
      whereas Cdh1 overexpression results in decreased pVHL expression. Taken together,
      these results suggest that pVHL is a novel substrate of APC/C(Cdh1). D box
      independent pVHL degradation was also detected, indicating that other ubiquitin
      ligases are also activated for pVHL degradation.

PMID- 20802537
TI  - Roles of bone morphogenetic protein-6 in aldosterone regulation by adrenocortical
      cells.
AB  - Aldosterone production occurs in the adrenal cortex, and is regulated primarily
      by angiotensin II (Ang II), potassium and adrenocorticotropin (ACTH). In the
      presence of the aldosterone stimulators, steroidogenesis is further governed by
      local autocrine and/or paracrine factors in the adrenal cortex. We reported the
      presence of functional bone morphogenetic protein (BMP) system in the adrenal
      cortex and also demonstrated that BMP-6 increases Ang II-induced aldosterone
      production, which could be involved in the "aldosterone breakthrough" phenomenon.
      Aldosterone breakthrough is the phenomenon by which circulating aldosterone
      concentrations increase above pre-treatment levels after long-term therapy with
      ACE inhibitors or Ang II type 1 receptor antagonists (ARB). This phenomenon may
      lead to important clinical consequences since increased aldosterone in a high
      salt state facilitates cardiovascular and renal damage in hypertensive patients.
      We found that long-term ARB treatment reverses the reduction of aldosterone
      synthesis by adrenocortical cells, thereby causing "cellular aldosterone
      breakthrough". The availability of BMP-6 in the adrenal cortex may be at least
      partly involved in the occurrence of cellular escape from aldosterone suppression
      under chronic treatment with ARB.

PMID- 20802538
TI  - Effects of imipramine and lithium on the suppression of cell proliferation in the
      dentate gyrus of the hippocampus in adrenocorticotropic hormone-treated rats.
AB  - We examined the influence of chronic adrenocorticotropic hormone (ACTH) treatment
      on the number of Ki-67-positive cells in the dentate gyrus of the hippocampus in
      rats. ACTH treatment for 14 days decreased the number of such cells. The
      administration of imipramine or lithium alone for 14 days had no effect in saline
      treated rats. The effect of ACTH was blocked by the administration of imipramine.
      Furthermore, the coadministration of imipramine and lithium for 14 days
      significantly increased the number of Ki-67-positive cells in both the saline and
      ACTH-treated rats. The coadministration of imipramine and lithium normalized the
      cell proliferation in the dentate gyrus of the hippocampus in rats treated with
      ACTH.

PMID- 20802536
TI  - Direct interaction between NHERF1 and Frizzled regulates beta-catenin signaling.
AB  - Although Wnt-Frizzled (Fzd) signaling is critical in the pathophysiology of
      carcinomas, its role in human breast cancer has been difficult to establish. We
      show here that the adaptor protein Na(+)/H(+) exchange regulatory factor1
      (NHERF1), a protein abundantly expressed in normal mammary epithelium, regulates
      Wnt signaling, maintaining low levels of beta-catenin activation. NHERF1's
      effects are mediated by direct interactions between one of its PSD-95/drosophila
      discs large/ZO-1 (PDZ) domains and the C-terminus of a subset of Fzd receptors.
      Loss of NHERF1 in breast cancer cell lines enhances canonical Wnt signaling and
      Wnt-dependent cell proliferation. Furthermore, the mammary glands of NHERF1
      knockout mice exhibit increased mammary duct density accompanied by increased
      proliferation and beta-catenin activity. Finally, we demonstrate a negative
      correlation between NHERF1 expression and nuclear beta-catenin in human breast
      carcinomas. Taken together, these results provide a novel insight into the
      regulation of Wnt signaling in normal and neoplastic breast tissues, and identify
      NHERF1 as an important regulator of the pathogenesis of breast tumors.

PMID- 20802539
TI  - General consumer awareness of warnings regarding the consumption of alcoholic
      beverages.
AB  - Over the past two decades, the liquor industry in Japan has strived to address
      alcohol-related problems through initiatives such as warnings in the various
      media. In this study, we conducted an Internet-based questionnaire survey to
      examine general consumer awareness of such warnings, and the media by which they
      are conveyed, on the consumption of alcoholic beverages. A total of 985 subjects
      (males: 487, females: 498) in age groups ranging from 20s to 70s responded
      (response rate: 22.4%). The awareness rates for warnings regarding underage
      drinking, drunk driving, and drinking during pregnancy, and those for messages
      encouraging moderation in drinking, were 96.4%, 83.7%, 59.6%, and 45.5%,
      respectively. Logistic regression analysis adjusted for habitual alcohol
      consumption demonstrated significant gender- and/or age-based differences in the
      rates of awareness of warnings and the media publicizing them. For example, the
      odds ratio of awareness among women of warnings against underage drinking was
      significantly higher than that of awareness among men. Issues that must be
      addressed in the future include:(1) increasing public awareness about messages
      regarding drinking during pregnancy and drinking in moderation;(2) reviewing the
      wording of warnings to make them more effective;and (3) devising and employing,
      on a regular basis, more effective means of transmitting messages in
      consideration of gender and age.

PMID- 20802540
TI  - Production of a transgenic mosquito expressing circumsporozoite protein, a
      malarial protein, in the salivary gland of Anopheles stephensi (Diptera:
      Culicidae).
AB  - We are producing a transgenic mosquito, a flying syringe, to deliver a vaccine
      protein to human beings via the saliva the mosquito deposits in the skin while
      biting. The mosquito produces a vaccine protein in the salivary gland (SG) and
      deposits the protein into the host's skin when it takes the host's blood. We
      chose circumsporozoite protein (CSP), currently the most promising malaria
      vaccine candidate, to be expressed in the SG of Anopheles stephensi. To transform
      the mosquitoes, plasmid containing the CSP gene under the promoter of female SG
      specific gene, as well as the green fluorescent protein (GFP) gene under the
      promoter of 3xP3 as a selection marker in the eyes, was injected into more than
      400 eggs. As a result, five strains of GFP-expressing mosquitoes were
      established, and successful CSP expression in the SG was confirmed in one strain.
      The estimated amount of CSP in the SG of the strain was 40 ng per mosquito. We
      allowed the CSP-expressing mosquitoes to feed on mice to induce the production of
      anti-CSP antibody. However, the mice did not develop anti-CSP antibody even after
      transgenic mosquitoes had bitten them several times. We consider that CSP in the
      SG was not secreted properly into the saliva. Further techniques and trials are
      required in order to realize vaccine-delivering mosquitoes.

PMID- 20802541
TI  - Long-term management of hepatitis C-seropositive subjects with AntiOxidant
      Biofactor (AOB), a fermented food supplement.
AB  - The efficacy of AntiOxidant Biofactor (AOB) for the management of apparently
      healthy subjects with chronic hepatitis C infection was investigated. A total of
      60 subjects (35 males, 25 females) participated in the trial. AOB was given
      orally in 2 packs (3 g per pack) 3 times per day. 17 subjects had taken AOB for 3
      years, 31 subjects up to 2 years, and 41 subjects up to one year. The initial
      mean (SD) serum alamine aminotransferase (ALT) level was 46.3+/-35.4 IU/L, and
      significant (p0.05, paired t-test) reductions in the mean serum ALT levels were
      observed at 6 months (38.6+/-21.5 IU/L), 18 months (31.9+/-18.1 IU/L), 2 years
      (31.2+/-14.6 IU/L), and 3 years (28.0+/-15.9 IU/L). Those presenting with high
      serum ALT levels (30 subjects) demonstrated significant levels (p0.05, paired t
      test) of reduction in the mean serum ALT levels at 6, 12, 18, 24, and 36 months
      of treatment. No side effects were observed and the AOB treatment was well
      tolerated by all subjects.

PMID- 20802542
TI  - Expression of antiangiogenic prolactin fragments in the placentas of women with
      pregnancy induced hypertension.
AB  - It has been reported that prolactin (PRL) is cleaved to 14 or 16 kDa fragments by
      cathepsin D in vitro and in vivo, and that such fragments exhibit antiangiogenic
      and proapoptotic properties. The aim of this study was to investigate the
      relationship between pregnancy induced hypertension (PIH) and the placental
      expression of antiangiogenic PRL fragments and cathepsin D. Placental expression
      of PRL fragments and cathepsin D was evaluated by Western blot analysis in a
      group of 9 pregnant women consisting of 5 normal pregnancies and 4 severe PIH
      cases. Antiangiogenic PRL fragments were detected in 4 placental samples from all
      PIH cases but not detected in those from normal pregnancies (p<0.05). The
      expression of cathepsin D in PIH placentas was significantly lower than that in
      those without PIH (p<0.05), while the placental expression of procathepsin D was
      significantly greater in PIH cases than in the normal pregnancies (p<0.05). These
      data suggest that antiangiogenic PRL fragments in the placenta may be present
      only in PIH cases, and that PRL fragments in the placenta might be implicated in
      the pathophysiology of PIH.

PMID- 20802543
TI  - Atypical lipomatous tumor of the tongue: report of a case.
AB  - The term atypical lipomatous tumor (ALT) is synonymous with well-differentiated
      liposarcoma (WDL). This tumor occurs very rarely in the tongue. Thus, it is
      difficult to predict its prognosis. Although recurrence of ALT/WDL is thought to
      be unlikely after complete excision, long-term follow-up is necessary when
      considering the pathologic conditions of this tumor at other sites. Here, we
      report a case of an ALT of the tongue, with a review of the literature. A 68-year
      old man was referred to our hospital because of a tumor on the left side of his
      tongue. Upon palpation, the tumor was 12mm in diameter, circumscribed, elastic
      and hard, well demarcated, movable, and painless. We diagnosed the lesion as a
      lipoma and extirpated the tumor under local anesthesia. Because the specimen was
      histopathologically diagnosed as an ALT, as a precaution, we excised an
      additional 5mm from the area surrounding the original tumor under general
      anesthesia. Three years after the operation, the tongue demonstrated good healing
      without paresthesia or dysfunction, and to date there has been no evidence of
      recurrence.

PMID- 20802545
TI  - Patents.
AB  - 4,942,580; 4,986,623; 4,996,884; 4,998,259; 5,001,716; 5,003,544; 5,003,567;
      5,011,284; 5,013,151; 5,018,810; 5,018,857; 5,018,859; 5,022,731; 5,022,760;
      5,026,131; 5,026,161; 5,027,367; 5,034,613; 5,034,951; 5,042,889; 5,048,026;
      5,048,938; 5,052,003; 5,052,011; 5,056,885; 5,058,972; 5,064,265; 5,064,284;
      5,064,288; 5,067,134; 5,068,525; 5,071,208; 5,074,665.

PMID- 20802544
TI  - Common acute lymphoblastic leukemia Ph+ following Langerhans cell histiocytosis
      in a multi-malformed child with INV (9) (p12;q13) (mat): case report.
AB  - The occurrence of Langerhans cell histiocytosis (LCH) and another malignancy in
      the same patient is infrequent but has been recognized. The genetic changes that
      could be responsible for LCH and/or concomitant leukemia development are obscure.
      To the best of our knowledge, this is the first description of constitutional
      maternally derived inv (9) (p12;q13) in an LCH patient, and also of the
      development of common ALL Ph after LCH diagnosis and therapy. The potential
      significance of these findings [inv (9)+LCH+ALL Ph+] and their mutual
      relationship are unknown. Therefore, cooperative studies of large numbers of
      patients are needed to identify the common risk factors, if any.

PMID- 20802546
TI  - Nasa patter.

PMID- 20802548
TI  - Simple and low-cost method for measuring the coherence time of ultrashort laser
      pulses.
AB  - A simple method for measuring the coherence time of ultrashort pulses is
      reported. The double reflection off a glass slide produces interference fringes
      that are used to calculate the coherence time.

PMID- 20802549
TI  - Pumping geometry for a grazing-incidence dye laser.
AB  - A new pumping geometry for longitudinal excitation of a grazing-incidenceg rating
      dye laser is proposeda nd experimentally demonstrated.

PMID- 20802550
TI  - Sun photometer with light-emitting diodes as spectrally selective detectors.
AB  - Light-emitting diodes can function as spectrally selective detectors in a
      miniature, inexpensive sun photometer that measures atmospheric turbidity and
      precipitable water.

PMID- 20802551
TI  - Technique to determine dominant radiative processes in low-pressure rare gas
      lasers.
AB  - We describe a technique to determine dominant radiative processes in rare gas
      lasers, with application to the He-Xe laser.

PMID- 20802552
TI  - Infrared spectroscopic measurements of tropospheric trace gases.
AB  - Absorption features of several trace gases have been detected in 0.017-cm -(1)
      resolution infrared spectra recorded over surface-level paths of 0.5 and 1.5 km
      at the National Solar Observatory on Kitt Peak, near Tucson, Arizona.
      Measurements of 0(3), HCOOH, NH(3), and H(2)CO are briefly discussed.

PMID- 20802553
TI  - Optical probe for on-line spectroscopic measurements in the near-critical region.
AB  - An optical probe is presented for concentration determinations by high-pressure
      spectroscopy in the near-critical region. Based on the constructive design, the
      radiation path within a pressure vessel is independent of the refractive index of
      the fluid media.

PMID- 20802554
TI  - Measurement of the NH(3), CCl(2)F(2), CHClF(2), CFCl(3), and CClF(3) absorption
      coefficients at isotopic (13)C(16)O(2) laser wavelengths by photoacoustic
      spectroscopy.
AB  - Owing to the linearity of the photoacoustic signal, the absorption coefficients
      of Freons were measured on isotopic (13)C(16)O(2) laser lines.

PMID- 20802555
TI  - Dye lasers: introduction by the feature editors.
AB  - This special issue of Applied Optics provides a perspective on recent trends in
      dye laser research.

PMID- 20802556
TI  - Cavity dispersion equation Deltalambda approximately Deltatheta( partial
      differentialtheta/ partial differentiallambda)(-1): a note on its origin.
AB  - A simple derivation of the cavity dispersion equation for high-gain pulsed
      lasers, Deltalambda approximately Deltatheta/ partial differentiallambda)(-1), is
      provided by using Dirac's notation for probability amplitudes as applied to the
      analysis of dispersive cavities.

PMID- 20802557
TI  - Long-term wavelength stabilization of a commercial pulsed dye laser.
AB  - An inexpensive device is described that stabilizes the wavelength of a commercial
      nanosecond-pulsed dye laser. The instrument monitors the frequency-dependent
      interference pattern that is generated when a portion of the dye laser output
      passes through an external Fabry-Perot etalon. In order to maintain a fixed
      wavelength, a personal computer adjusts the dye laser's grating position when the
      interference pattern indicates that a shift in laser wavelength has occurred.
      Tests indicate that this device reduces the drift of the laser's mean wavelength
      to < 0.0001-nm/ degrees C ambient temperature change. The feedback mechanism
      incorporated in this design can sustain stationary frequency stabilization for
      indefinite periods of time.

PMID- 20802558
TI  - Mode structure fluctuations in a pulsed dye laser.
AB  - We have measured and analyzed high-resolution single-pulse spectra of a typical
      commercial dye laser. The longitudinal mode structure was resolved by using a
      Fizeau interferometer as the spectrum analyzer. In mode intensities we observed
      strong pulse-to-pulse fluctuations that are caused mainly by the variations of
      the spontaneous emissions to the laser modes during the starting phase of the
      laserpulse. Apart from the quantum noise, frequency jitter, i.e., shifts of the
      whole frequency comb, was also observed. The jitter appeared to be very fast, of
      the order of a few megahertz and hence cannot be explained by technical noise
      alone. A detailed knowledge of the spectral fluctuations is needed in theoretical
      models of noise effects in nonlinear spectroscopy. It can also be applied to
      novel noise reduction techniques.

PMID- 20802559
TI  - High-average-power dye laser at Lawrence Livermore National Laboratory.
AB  - The copper-laser-pumped dye laser system developed at the Lawrence Livermore
      National Laboratory (LLNL) is now capable of sustained, efficient, and reliable
      operation at total powers exceeding 2500 W and single amplifier chain powers
      exceeding 1300 W. Wavelength center frequency stability is maintainable to < 50
      MHz. Laser dyes developed at LLNL permit tunability from 550 to 650 nm. Wave
      front quality is < lambda/4 peak to valley. The system is operated remotely with
      the aid of a comprehensive set of diagnostics. Besides supporting its primary
      atomic-vapor-laser-isotope-separation mission, the system is being used in
      alternate applications such as materials processing and the generation of
      artificial guide stars.

PMID- 20802560
TI  - Small-signal gain and saturation intensity in dye laser amplifiers.
AB  - Small-signal gain and saturation intensity are obtained from input and output
      intensity measurements in a dye amplifier stage in which amplified spontaneous
      emission changes the amplifier performance. We demonstrate that these
      measurements lead to more accurate values for the effective gain of the amplifier
      than what can be obtained from theoretical calculations by using physical
      parameters of the dye. Furthermore, this method can be used to optimize the power
      extraction efficiency for a dye amplifier stage transversely pumped by a copper
      vapor laser.

PMID- 20802561
TI  - Complete optical analysis of an UV laser dye using saturation techniques.
AB  - The saturation properties of an UV laser dye, 3,5,3,5-tetra-t-butyl-p-sexiphenyl
      (TBS), pumped by a XeCl laser were studied. The experimental data included
      measurements of the optical saturation of transmission and amplifier gain. The
      data were fit directly to photon propagation differential equations to obtain the
      saturation intensities for absorption and emission. From the measured saturation
      parameters a complete determination was made of the optical constants of the
      singlet states in TBS. The results presented include the absorption spectrum,
      fluorescence spectrum, fluorescence lifetime, excitedstate absorption cross
      sections at the pump laser and dye laser wavelengths, quantum yield, wavelength
      dependence of the stimulated emission cross section, and an upper bound for the
      intersystem crossing rate. The saturation analysis method provides a rapid
      experimental evaluation of a laser dye with high accuracy. A two-photon excited
      transition at the long wavelengths of the laser oscillator tuning range of TBS
      produces photochemical degradation. The photochemical degradation rate increases
      with increasing wavelength.

PMID- 20802562
TI  - Jones matrices of tilted birefringent plates in atunable dye laser: modes at low
      gain and temperature effects.
AB  - The Jones matrices of tilted birefringent plates that are used as a tunable
      device in a laser cavity are established in order to compute the resonance modes.
      The results are compared with experimental spectra of a dye laser that contains
      this device at low gain. The temperature effect on the filter is also described.

PMID- 20802563
TI  - Phase locking counterrotating modes of a broadband ring dye laser.
AB  - We present the results of an experimental study of phase locking counterrotating
      modes in a Rhodamine-6G continuous-wave broadband ring dye laser. Results for the
      measured mutual coherence of the counterrotating fields are presented for three
      different coupling geometries: namely, coupling by using an intracavity
      retroreflector, a single extracavity retroreflector placed in one of the output
      beams,and extracavity retroreflectors placed in each of the two output beams. We
      find that the highest degree of locking is obtained for the case of the
      intracavity retroreflector and leads to counterrotating outputswith a measured
      mutual coherence of unity.

PMID- 20802564
TI  - Diode-pumped dye laser analysis and design.
AB  - We investigate the feasibility and perform an analysis of diode pumping organic
      dye lasers. From a number of candidate laser dyes operating in the visible (red)
      to near-infrared spectrum, we select two dyes that appear most suited for
      pumpingby commercially available diode lasers. Detailed characterization of these
      two dyes provides critical laser parameters. A cw dye laser design is analyzed
      and optimized by using these parameters. Possible extension to pulsed laser
      operation is also presented.

PMID- 20802565
TI  - Generation of intense 10-ps, 193-nm pulses using simple distributed feedback dye
      lasers and an ArF(*) amplifier.
AB  - A pair of holographic distributed feedback dye lasers is used to generate 10-ps
      pulses at two selected wavelengths that are mixed in a BBO crystal to produce a
      pulse ~ 10 ps in duration at 193 nm. This seed pulse is subsequently amplified in
      an ArF(*) excimer laser to an energy of 10-15 mJ with <40 microJ in amplified
      spontaneous emission. The pulses are nearly transform limited and diffraction
      limited.

PMID- 20802566
TI  - Generation of tunable subpicosecond pulses using low-Q dye cavities.
AB  - The design and operation characteristics of a low-Q cavity dye laser chain pumped
      by a single laser (seeded Q-switched Nd:YAG) for generating high-power tunable
      subpicosecond pulses are presented. Two low-Q short dye cavities in cascade
      pumped well above threshold followed by extracavity pulse shaping in a highly
      saturated absorber and amplifiers lead to stable generation of single 500-fs
      pulses, i.e., a pulse-shortening factor > 10(4) (from a smooth 6-ns pump pulse).
      Output pulse energies of 500 microJ (1-GW peak power) are produced from 40-mJ
      pump energy and used to generate high-power tunable subpicosecond pulses from 450
      to 700 nm by supercontinuum generation, spectral selection, and amplification in
      dye amplifiers pumped by the same Nd:YAG laser. The spectral and time processes
      involved in these pulse-shortening methods are discussed with a rate-equation
      model.

PMID- 20802567
TI  - Spectral broadening and compression of femtosecond light pulses that pass through
      dye amplifiers.
AB  - The amplification of femtosecond light pulses in multistage as well as in
      traveling-wave dye amplifiers is studied numerically, taking into account group
      velocity dispersion, self-phase modulation that is due to Kerr-type nonlinearity,
      and gain depletion. The combined action of these processes results in a spectral
      broadening that can be utilized for pulse compression. The results are compared
      with experimental findings.

PMID- 20802568
TI  - Theoretical analysis of contributions of self-phase modulation and group-velocity
      dispersion to femtosecond pulse generation in passive mode-locked dye lasers.
AB  - The influence of self-phase modulation (SPM) and group-velocity dispersion (GVD)
      on pulse development in a passive mode-locked dye laser is investigated
      numerically by using fast Fourier transformations. The situation of positive SPM
      is considered. Four regions of laser performance may be distinguished: (i) In the
      positive GVD region pulse broadening by GVD must be balanced by the pulse
      shortening effect of the saturable absorber. (ii) In a region around zero GVD the
      laser is periodically self-quenching and the temporal and spectral pulse shapes
      change periodically similar to higher-order solitons. (iii) It follows a negative
      GVD region where stable pulses of smooth temporal and spectral shapes are
      generated similar to fundamental solitons. In this region the pulse duration is
      practically independent of the saturable absorber concentration, and the
      saturable absorber is needed mainly for background suppression. (iv) Further
      increasing the negative GVD, pulse broadening must be balanced by the saturable
      absor ber pulse shortening.

PMID- 20802569
TI  - Lloyd's mirror as a laser wavemeter.
AB  - A simple Lloyd's mirror interferometer and a CCD photodiode array make a compact
      Fourier transform wavemeter for pulsed lasers. A transformation from the
      nonlinear spatial sampling of the diodes to a linear temporal series is described
      that sharpens the distribution in the spectral domain and permits long diode
      arrays to be used in the interferometer. Tests with a tunable red dye laser show
      that the wavemeter has an accuracy of 2 cm(-1) and the sensitivity to record
      untuned superradiant emission from the dye as well as frequency doubling in the
      ultraviolet.

PMID- 20802570
TI  - Laser dye spectroscopy of some pyrromethene-BF(2) complexes.
AB  - To improve the laser action properties of the pyrromethene-BF(2) (P-BF(2))
      complexes, we studied substitution effects at different positions of the dye
      molecule on the electronic spectra of several derivatives. Specifically, we used
      laser photoselection spectroscopy to measure the triplet-triplet (T-T) absorption
      and polarization spectra as well as the fluorescence and visible absorption
      singlet-singlet (S-S) spectra of the following compounds: 1,2,3,5,6,7,8
      heptamethyl; 8-acetoxymethyl-1,3,5,7-tetramethyl-2,6-diethyl; 1,3,5,7-tetramethyl
      8-p-methoxyphenyl; 3,5-dimethyl-1,7-diphenyl; and 1,3,5,7,8-pentamethyl- 2,6
      diphenyl P-BF(2) complexes. The 1,3,5,7-tetramethyl P-BF(2) complex itself
      exhibits weak T-T absorption, which stretches from the green to the near-IR
      spectral region. This band consists of two overlapping (differently polarized) T
      T transitions. Short molecular axis (i.e., 8 and 1,7 positions) substitution
      causes the positively polarized T-T transition to gain considerably in intensity.
      Significantly, the negatively, long-axis-polarized T-T transition was unaffected
      by the long-axis 2,6- position disubstitution. Therefore, only the 2,6-position
      disubstitution is expected to produce superior new P-BF(2) complex laser dyes.
      Substitution effects from strongly interacting groups with chromophores on S-S as
      well as T-T absorption spectra, together with cw laser photoselection
      spectroscopy, are briefly reviewed.

PMID- 20802571
TI  - Continuous-wave dye lasers in the DCM region.
AB  - Laser dye DCM in an ethylene glycol solution is a favored medium for converting
      the argon-ion 488- and 514-nm pump lines to tunable radiation in the 600-730-nm
      region. However, the dye precipitates from solution, is a powerful mutagen, and
      the glycol solvent is hygroscopic. Replacement dyes in 3-phenyl-1- propanol or 2
      phenoxyethanol, particularly the latter, are proposed.

PMID- 20802572
TI  - Potential and limitations of energy-transfer processes in pulsed and cw dye laser
      mixtures: comparison of theory and experiments.
AB  - A comprehensive energy-transfer dye laser (ETDL) simulation model and the premise
      on which it is based are examined and reviewed. The model permits theoretical
      predictions of the total transfer efficiency and hence identification of the
      appropriate mechanisms that are responsible for energy transfer as well as
      predicting fluorescence spectra of dye mixtures. Using concentration regimes that
      are generally applicable to laser action, we also show that the model is capable
      of predicting gain line shapes (and hence tunability) for pulsed ETDL's. An
      extension of the model also predicts the gain spectrum of cw laser-pumped ETDL's
      as a function of donor and acceptor concentrations, their spectral data,
      energytransfer parameters, pump power and wavelength, and dimensions of the
      active region. Model simulation results are checked against experimental results
      for pulsed and cw ETDL's with laser outputs in the visible and near-IR spectral
      regions. The results lead to a better and more detailed understanding of ETDL mec
      hanisms and the role that the triplet states play in these mechanisms.

PMID- 20802573
TI  - Alternative configuration for refracted near-field measurements of refractive
      index on glass-integrated-optics waveguides.
AB  - We present experimental investigations of two configurations for refractive-index
      profiling and for geometry measurements of glass-integrated waveguides with the
      refracted near-field technique. An original configuration is proposed that
      simplifies the measurement cell and the handling.

PMID- 20802574
TI  - Independent measurement of extinction and backscatter profiles in cirrus clouds
      by using a combined Raman elastic-backscatter lidar.
AB  - Height profiles of the extinction and the backscatter coefficients in cirrus
      clouds are determined independently from elastic- and inelastic- (Raman)
      backscatter signals. An extended error analysis is given. Examples covering the
      measured range of extinction-to-backscatter ratios (lidar ratios) in ice clouds
      are presented. Lidar ratios between 5 and 15 sr are usually found. A strong
      variation between 2 and 20 sr can be observed within one cloud profile. Particle
      extinction coefficients determined from inelastic-backscatter signals and from
      elastic-backscatter signals by using the Klett method are compared. The Klett
      solution of the extinction profile can be highly erroneous if the lidar ratio
      varies along the measuring range. On the other hand, simple backscatter lidars
      can provide reliable information about the cloud optical depth and the mean cloud
      lidar ratio.

PMID- 20802575
TI  - Hybrid inelastic-scattering models for particle thermometry: unpolarized
      emissions.
AB  - A hybrid modeling technique is reported for studying inelastic (Raman and
      fluorescent) scattering from molecules embedded in spherical particles of large
      optical size parameters. The modeling technique, which combines the Lorenz-Mie
      theory (for determination of the incident excitation field) with a geometric
      optics formulation (for determination of an inelastic-scattering efficiency
      function), permits predictions of a weighting function inside a particle and also
      the angular scattering patterns. These calculations provide insight into the
      scattering processes and may serve as a theoretical basis for guiding experiments
      and interpreting results in aerosol particle thermometry by using inelastic
      scattering techniques.

PMID- 20802576
TI  - Hybrid inelastic-scattering models for particle thermometry: polarized emissions.
AB  - The work of a previous paper [Appl. Opt. 31, 7132 (1992)] is extended to the case
      of polarized inelastic (Raman and fluorescent) scattering from molecules embedded
      in spherical particles of large optical size parameters. The hybrid modeling
      technique, which combines the Lorenz-Mie theory with a geometric optics method,
      accounts for the contributions of directly transmitted rays as well as reflected
      transmitted rays of secondary emissions. Coherent effects of light rays emitted
      from a single point source are considered in the model. The angular scattering
      patterns predicted with the modeling technique are consistent with expected
      physical behavior and results from classical solutions. This work has a direct
      impact on studies of particle thermometry and particle diagnostics in which
      inelastic-scattering techniques are beginning to be applied.

PMID- 20802577
TI  - Examination of the polished surface character of fused silica.
AB  - Investigation of the surface character of fused silica polished with various
      compounds dispersed in water identified pH 4 as the optimum condition for high
      quality. Analyses support the conclusion that at this pH redeposition of hydrated
      material onto the surface during polishing is limited. Comparative polishing
      results for Zerodur are included. Improvement of the laser-damage threshold of a
      coating on the pH 4 polished fused silica is suggested.

PMID- 20802578
TI  - Surface normal rotation: a new technique for grazing-incidence monochromators.
AB  - A class of fixed-slit monochromator that scans wavelength over a broad region
      using a grazing-incidence diffraction grating that rotates about its surface
      normal is described.

PMID- 20802579
TI  - Thermal apparent-strain sensitivity of surface-adhered, fiber-optic strain
      gauges.
AB  - We have derived, based on established practice in experimental mechanics, an
      equation for calculating the thermal apparent-strain sensitivity of phase
      modulated, surfaceadhered, adhered, fiber-optic strain sensors. This formulation
      permits the thermal performance of fiber-optic strain gauges to be compared with
      conventional resistive gauges. This sensitivity for commonly used fiber-optic
      sensors is summarized.

PMID- 20802580
TI  - Reset-free system for real-time polarization control and synthesis.
AB  - A reset-free polarization controllsynthesis system is described. The desired
      polarization state can be selected by keyboard control with no insertion or
      rearrangement of optical components.

PMID- 20802581
TI  - Measurement of Mueller matrices: erratum.

PMID- 20802582
TI  - Calculation of the effective index for nonguiding regions.
AB  - When the effective-index method is used to reduce a three-dimensional refractive
      index distribution to two dimensions, e.g., for use with the two-dimensional beam
      propagation method, strictly speaking, the effective index n(eff) cannot be
      calculated for nonguiding regions. Here a technique for obtaining values of
      n(eff) in such regions is described. The method begins with the index
      distributions in regions for which values of n(eff) are calculable and then
      perturbs them for those regions of interest. Using an electro-optic Y-branch
      optical modulator and a voltage-induced optical waveguide modulator as examples,
      we demonstrate this method and compare predicted results with measured results.

PMID- 20802583
TI  - Optical metrology for two large highly aspheric telescope mirrors.
AB  - We describe a relatively simple, but highly effective, approach to the system
      design and alignment of an all-refractive Offner null corrector and phase
      measuring Shack cube interferometer. In addition we outline procedures for
      fabricating and testing the optical components. Allowable errors for all
      parameters are determined by a tolerance analysis that separates axisymmetric and
      residual figure errors. An open construction optics frame provides a high degree
      of metering flexibility by incorporating simple kinematic mounts that provide
      adjustment of each lens while also allowing the lens to be removed and replaced
      with <2microm absolute repeatability. Nonaxisymmetric alignment errors are
      removed by rotating the optics on a high-precision bearing. Axial spacings are
      measured with contact transducers attached to both ends of an Invar metering rod.
      Two completed systems have guided the stressed-lap polishing of 1.8-m f/ 1.0 and
      3.5-m f/ 1.5 aspheric mirrors.

PMID- 20802584
TI  - Modulation transfer function measurement technique for small-pixel detectors.
AB  - A modulation transfer function (MTF) measurement technique suitable for large
      format, small-pixel detector characterization has been investigated. A volume
      interference grating is used as a test image instead of the bar or sine wave
      target images normally used. This technique permits a high-contrast, large-area,
      sinusoidal intensity distribution to illuminate the device being tested, avoiding
      the need to deconvolve raw data with imaging system characteristics. A high
      confidence MTF result at spatial frequencies near 200 cycles/mm is obtained. We
      present results at several visible light wavelengths with a 6.8-microm-pixel CCD.
      Pixel response functions are derived from the MTF results.

PMID- 20802585
TI  - Bolometric detectors: optimization for differential radiometers.
AB  - A differential radiometer can be constructed by placing two matched bolometric
      detectors in an ac bridge, thus producing a signal that is proportional to the
      difference in power incident on the two detectors. In conditions of large and
      time-varying common-mode radiative load, the common-mode response resulting from
      imperfectly matched detectors can limit the stability of the difference signal.
      For semiconductor thermistor bolometers we find that the bridge can always be
      trimmed to null the common-mode response for a given instantaneous value of the
      radiative load. However, subsequent changes in the commonmode radiative load
      change the operating point of the detectors, giving rise to a second-order common
      mode response. This response can be minimized by increasing the electrical-power
      dissipation in the detectors at the cost of sensitivity. For the case that we are
      analyzing, and for mismatches in detector parameters that are typical of randomly
      paired detectors, common-mode rejection ratios in excess of 10(3) can be achieved
      under 20% changes in radiative load.

PMID- 20802586
TI  - Characterization of an absolute cryogenic radiometer as a standard detector for
      radiant-power measurements.
AB  - An active cavity radiometer of the electrical substitution type with a cone
      receiver that operates at 2-4 K has been developed for measuring radiant fluxes
      in the dynamic range of 20 nW to 100 microW within an uncertainty of +/-1%
      (2sigmalevel). It is a broadband absolute detector with a flat overall absorption
      efficiency that is >99% for radiation from the visible to long-wavelength IR. The
      system is designed based on thermal modeling and experimental measurements of
      concepts. It has been installed in the cryogenic chamber for low-background
      infrared radiation calibrations at the National Institute of Standards and
      Technology (NIST) for testing cryogenic blackbody sources, detectors, and optical
      components. Its time constant, responsivity, and nonequivalence error have been
      measured. They are in agreement with design predictions. Radiant power
      measurements of an amplitude-stabilized He-Ne laser beam with the radiometer and
      an industry standard photodiode detector, QED-200, have been intercompared and
      found to be in agreement. The intercomparison ratio of the measurements with the
      absolute cryogenic radiometer and QED-200 was 1.004 in the 75-100-microW range
      with an uncertainty of 0.5% (the 3sigma level).

PMID- 20802587
TI  - International intercomparison of detector responsivity at 1300 and 1550 nm.
AB  - An intercomparison of spectral responsivity measurements has been carried out
      among the national laboratories of 13 countries. Measurements were made at
      wavelengths of 1300 and 1550 nm, which are important in optical communication
      systems. Three germanium photodiodes were circulated in each of three separate
      paths, beginning and ending at the National Institute of Standards and Technology
      as the coordinating laboratory. The results show agreement within 1%.

PMID- 20802588
TI  - Loss mechanisms in optical light pipes.
AB  - A geometrical optics approach is used to develop a theoretical model for
      analyzing loss mechanisms in optical light pipes. Five mechanisms are identified:
      intrinsic absorption, bulk scattering, losses that are due to roughness at the
      core-cladding interface, losses that are due to large-scale defects at the core
      cladding interface, and losses that are due to absorption in the cladding
      material; and the effects of each of these on light-pipe transmission are
      considered. An approximate model appropriate for slightly rough surfaces is used
      to estimate the loss that is due to interface roughness. Optical experiments on
      commercially available light pipes are done to quantify the various loss
      processes. These experiments indicate that the interface effects play an
      important role in limiting the transmission in high-quality light pipes. From the
      optical measurements a rms interface roughness height in the 30-70-A range is
      deduced, and these values are confirmed by direct surface profilometry with an
      atomic force microscope.

PMID- 20802589
TI  - Differential type of phase-locked laser diode interferometer free from external
      disturbance.
AB  - A phase-locked laser diode interferometer with differential detection to
      eliminate external disturbance is proposed. In this interferometer, the
      measurements are implemented at two different points at the same time. The
      surface profile that contains the disturbance is obtained at the scanned
      measuring point, and the disturbance is obtained at the fixed measuring point.
      The exact profile is obtained by subtracting the latter from the former. The
      limitations and characteristics are examined theoretically. The analytical
      results agree well with the experimental results. The repeated measurement
      accuracy is estimated to be ~5 nm in this interferometer.

PMID- 20802590
TI  - Determination of refractive properties of fluids for dual-wavelength
      interferometry.
AB  - Methods to calculate the refractive properties of solutions at different
      wavelengths are described by using experimental data at just two wavelengths. The
      properties are the refractive index and its gradients with temperature and
      concentration. Cauchy's equation is used to determine the refractive indices. The
      gradients versus temperature and concentration are then determined by using the
      Murphy-Alpert and the Lorentz-Lorenz equation, respectively. Finally, the
      particular case of a triglycine sulfate aqueous solution is considered as an
      example. The approach should provide the desired information for fringe analysis
      when dual-wavelength holographic or other interferometry is used for solving heat
      and mass transfer problems in fluids during crystal-growth experiments.

PMID- 20802591
TI  - Direct readout of dynamic phase changes in a fiber-optic homodyne interferometer.
AB  - A novel time-domain method is described in which the dynamic phase modulation
      index applied to an interferometer is directly measured from the waveform of the
      output photocurrent of the interferometer. A dynamic phase deviation as high as
      78 rad has been experimentally demonstrated with a minimum detectable phase
      deviation of ~0.3 rad.

PMID- 20802592
TI  - Scalable aspheric corrective mirror for end-pumped solid-state lasers.
AB  - A procedure is presented to design an aspheric corrective mirror to remove the
      effects of thermally induced optical aberrations in end-pumped solid-state
      lasers. The design is based on solving the inverse problem of bending a thin
      plate of variable thickness; i.e., given the plate deflection profile a thickness
      profile must be calculated by solving the differential equation for bending. The
      advantage of this type of aberration correction is the fact that it can be scaled
      to different pump powers during operation while still matching the aspheric
      profile in question. Guidelines for fabrication of the mirror are also presented.

PMID- 20802593
TI  - Shared aperture for two beams of different wavelength using reflective phase
      gratings and the Talbot effect.
AB  - A shared aperture system for two laser beams with different wavelengths and
      composed entirely of reflective phase gratings is described. Beams that share an
      aperture are collinear, and they have the same transverse phase profile across
      the aperture as their respective sources. Using the Talbot effect that is
      observed in Fresnel diffraction from periodic objects, we preserve the phase of
      the beams, and we maximize the efficiency of the system. An experimental Talbot
      shared aperture system using He-Ne and He-Cd beams has an efficiency of 88.1% for
      the He-Ne beam and 70.3% for the He-Cd beam. These measured efficiencies agree
      well with theoretical predictions and computer simulations.

PMID- 20802594
TI  - Methods of choosing sample rays in ray-tracing computations.
AB  - Ray-tracing computations for calculating the fraction of radiant energy
      (intercept factor I) transmitted by an optical system are often performed by
      using the Monte Carlo method, i.e., selection of sample rays at random. However,
      this is not economical regarding computing time since the error E in I is
      proportional to N(-(1/2)), where N is the number of rays traced. It is found
      that, in example computations, the selection of sample rays according to a
      regular grid gives better results. An equation for estimating E in this case is
      derived on a theoretical basis and agrees with the computations. This predicts E
      alpha N(-(3/4)) for systems where three ray coordinates are needed (e.g., with
      rotational symmetry) and E alpha N(-?) where four are required, which is the
      general case.

PMID- 20802595
TI  - Sensing refractive-turbulence profiles (C(n)(2)) using wave front phase
      measurements from multiple reference sources.
AB  - A new technique for sensing refractive-turbulence profiles is described. The
      technique is based on performing a spatial correlation of the measured wave front
      phase from two reference sources. This technique is unique in that the
      correlation properties of the wave front phase are used instead of the more
      common approach of using optical scintillations. The geometry between the
      reference sources and the two wave front sensor apertures is arranged such that
      the two optical paths cross at some point in front of the sensor plane. The wave
      front phase for each reference source is reconstructed from the measured wave
      front sensor data. A spatial correlation of the two reconstructed phase maps is
      performed. From this correlation we are able to extract a measure of the
      structure constant of the refractive-index fluctuations C(n)(2). The resolution
      of the technique depends on the angle between the optical paths, the spatial
      frequency response of the wave front sensors, as well as the size of the wave
      front sensorapertures. For sensing the vertical profile of C(n)(2), we can obtain
      resolution of the order of 100 m by using sources separated by 1.15 degrees .

PMID- 20802596
TI  - Aligning lithography on opposite surfaces of a substrate.
AB  - Equipment has been developed for aligning lithographic features between opposite
      surfaces of substrates to within 1 microm. It will work with opaque substrates
      and allows registration to existing features on the other surface.

PMID- 20802597
TI  - Dual-sided lithography: a method for evaluating alignment accuracy.
AB  - We describe a method for measuring the accuracy of aligners used to align
      lithographic patterns on opposite sides of a substrate (back-to-front aligners).
      The method, with minor modifications, can also be used as an aid in performing
      back-to-front alignments. The method is based on interferometric principles, is
      insensitive to manufacturing errors, and is simple to implement. The version
      described in this paper is fabricated by using binary optics technology and can
      measure the accuracy of aligners to +/-0.2 microm.

PMID- 20802598
TI  - Full-field vibrometry using a Fabry-Perot etalon interferometer.
AB  - A solid lithium niobate Fabry-Perot etalon interferometer has been investigated
      with regard to its potential to perform full-field vibrometry. Predictions of
      theoretical system sensitivity were made based on signal-to-noise calculations.
      Optimized equations governing the etalon behavior were developed and examined in
      light of experimental results. The ability of the etalon system to accomplish
      multiple- (two-)-point simultaneous detection and full-field scanned vibrometry
      was demonstrated experimentally as well. The possibility of future work to obtain
      a snapshot image of an ultrasonic wave front is discussed.

PMID- 20802599
TI  - Optical properties of glasses in the ZnO-CdO-SiO(2) ternary system.
AB  - The optical properties of new glasses in the ZnO-CdO-SiO(2) system containing
      high CdO levels (50-90 wt. %) has been determined. The refractive-index variation
      versus CdO and ZnO composition has been considered. Likewise, the refractive
      index and spectral transmittance in the 200-2600-nm range for these glasses has
      been carried out. From these optical measurements it can be stated that glasses
      in the ZnO-CdO-SiO(2) system would be adequate for infrared windows or as laser
      matrices.

PMID- 20802600
TI  - Optical constants of polyimide films in the soft x-ray region from reflection and
      transmission measurements.
AB  - Measurements were performed with synchrotron radiation on free-standing, ~300-nm
      thick polyimide films in the photon energy range of 40-1350 eV. We evaluated
      optical constants both from transmission measurements with the Kramers-Kronig
      analysis and from multiangle reflection measurements by fitting Fresnel equations
      modified by two different roughness factors for both sides of the film. A
      thorough error analysis was carried out for both methods. The results agree well
      within the error barsthereby strengthening confidence in the applied theoretical
      formalism as well as in the experimental method in this difficult spectral
      region.

PMID- 20802601
TI  - General ray-tracing formulas for crystal.
AB  - I develop a new method of ray tracing that can be used to analyze the refraction
      or reflection of rays by both uniaxial and biaxial crystals.

PMID- 20802602
TI  - Nonimaging compound parabolic concentrator-type reflectors with variable extreme
      direction.
AB  - The properties of nonimaging compound parabolic concentrator (CPC)-type devices
      are examined in which the extreme direction is not constant but rather is a
      variable that can change along the reflector. One can then retain the maximal
      concentration or radiative efficiency of the CPC while the flux map on the
      absorber or target is modified, depending on whether the device is used for
      optical concentration or for lighting. Two general classes of reflector are
      derived, and all the nonimaging devices developed to date are shown to be special
      cases of the general solution. These two classes are the nonimaging analog of
      converging and diverging devices of imaging optics.

PMID- 20802603
TI  - X-ray focusing using microchannel plates.
AB  - We present measurements of the x-ray focusing properties of square-pore
      microchannel plates (MCP's). Square-pore MCP's contain large numbers of closely
      packed optical surfaces, as required for grazing incidence x-ray optics. The
      surface of individual MCP channels has been measured and found to have high
      microroughness transverse to the channel axis and low microroughness parallel to
      the axis. The high frequency transverse roughness, on length scales greater than
      400 nm, has a rms value of 5.9 nm and a Gaussian autocorrelation function with
      correlation length of 1.41 microm. We find that the geometric misalignments of
      the surfaces of different channels limit the angular resolution obtainable with
      current samples of MCP's to 7.1 arcmin.

PMID- 20802604
TI  - Differential optical microscopy based on higher-order Gaussian-Hermite beam
      patterns.
AB  - A new method for performing scanning differential optical microscopy is
      described. This method is based on the use of a higher-order transverse mode of a
      laser. The technique is capable of responding to both amplitude and phase
      structures on the object. The sensitivity of the system in detecting differential
      object phase structures is similar to that of a dc scanning Nomarski microscope.
      The system is employed to image the surface structure of an integrated circuit.

PMID- 20802605
TI  - Projection moire fringe pattern prediction using the optical transfer function in
      the presence of aberrations.
AB  - Theoretical treatment of the projection moire fringe pattern by using the optical
      transfer function (OTF) is presented. In general, primary Seidel aberrations are
      used to describe the effect of single aberrations on the OTF. In the case of a
      real lens system the actual OTF is computed from system parameters. This approach
      provides an insight into the formation of projection moire fringe patterns and
      accurately predicts their form including the contrast. For a real lens system
      experimental verification of the theoretical results, in the case of contrast,
      has shown good agreement between theory and experiments.

PMID- 20802606
TI  - Applications of optical logic-operated moire in moire topography and
      deflectometry.
AB  - The optical logic-operated moire is a new method to extract a specific moire
      pattern. It has the capabilities of eliminating original carrier frequencies,
      increasing the contrast, and narrowing the fringes. We introduce its applications
      in moire topography and deflectometry and also present the experimental results.

PMID- 20802607
TI  - Optical fiber sensing with a low-finesse Fabry-Perot cavity.
AB  - A detailed comparison between a low-finesse Fabry-Perot cavity and a typical two
      beam interferometer is developed and checked experimentally. The consequences of
      approximating the true Fabry-Perot function by the two-beam function are
      evaluated for commonly used signal-processing schemes in order to quantify the
      final error introduced in various fiber sensing schemes employing this
      configuration.

PMID- 20802608
TI  - Optical constants of thin silicon films near the silicon L(2,3) absorption edge.
AB  - Using synchrotron radiation, we determined the optical constants of thin silicon
      films in the wavelength region near the silicon L(2,3) absorption edge. The
      extinction coefficient was determined from the transmittance of a thin, unbacked
      silicon film. The refractive index was determined from the reflectance of a
      sample consisting of an evaporated silicon film on gold. The thickness of the
      evaporated silicon film was chosen so that an interference feature appeared in
      the wavelength region above the edge where the silicon is transmissive. The shape
      of the interference feature is sensitive to the optical constants of silicon near
      the edge.

PMID- 20802609
TI  - Fringe pattern in holographic interferometry for thermal expansion
      characterization of anisotropic bodies.
AB  - The fringe pattern produced in a double-exposure hologram by thermal expansion of
      anisotropic flat plates is theoretically attained and experimentally checked.

PMID- 20802610
TI  - Binary phase modulation properties of a programmable liquid-crystal television
      display.

PMID- 20802611
TI  - Optical dispersion technique for time-delay beam steering.

PMID- 20802612
TI  - Real-time measurement of wavelength selectivity of reflection holograms.

PMID- 20802614
TI  - Visualization of in-plane displacement fields by using phase-shifting holographic
      moire: application to crack detection and propagation: erratum.

PMID- 20802613
TI  - Particle image velocimetry fringe processing using an optically addressed spatial
      light modulator.

PMID- 20802615
TI  - Possibilities and limitations of space-variant holographic optical elements for
      switching networks and general interconnects.
AB  - Space-variant optical elements are necessary for realizing optical interconnects
      of arbitrary design. For such applications, planar holographic optical elements
      offer the highest degree of flexibility and ease of production; however their
      diffraction-based operation gives rise to chromatic aberrations. Here estimates
      for the number of independent space-variant interconnects, their spatial
      tolerances, and their wavelength stability are considered for close-cascade, and
      related, geometries.

PMID- 20802616
TI  - Use of laser-diode arrays in holographic interconnections.
AB  - Holographic interconnection schemes for high-speed data transfer have been
      demonstrated by other researchers. Because holographic recording materials
      presently available are sensitive to the visible spectrum but not to the near
      infrared, these studies used bulky gas lasers. Visible laser diodes, as they
      become available, will likely become a preferred source in a practical system
      because of their small size and high beam powers. The two mutually coherent beams
      needed to write the hologram have previously been implemented by using bulk
      optics to split a beam. In anticipation of the use of coherently coupled visible
      laser diode arrays as sources, it is shown that the individual elements of laser
      diode arrays currently available have sufficient mutual coherence to create
      reasonable holographic elements. This application is demonstrated with an
      infrared array because of the unavailability of visible arrays in this emerging
      technology. It is extrapolated that for visible coherently coupled laser diode
      arrays and current holographic materials, a holographic interconnection system is
      potentially feasible by using the mutually coherent beams from individual facets.
      This makes recording holograms more straightforward because the recording process
      eliminates beam splitting requirements. Therefore the system is more desirable
      for in situ recording situations such as those required for dynamic
      interconnection.

PMID- 20802617
TI  - Application of the mode approximation to reconstruction holography.
AB  - The result of holographic processing is described by using the well-known mode
      approximation. This approximation yields new expressions for degenerate read
      write holography in the optically thick scattering regime in the case in which
      many transverse modes are occupied. The approach differs from those of previous
      efforts by the inclusion of the effect of multiple dynamic gratings. The
      presentation makes clear the limitations of the practical applicability and the
      mathematical validity of the new result in relation to the better known regimes,
      using various approximations to predict the lowest-order fields. The application
      of reconstruction holography to aberration compensation is specifically
      considered. The effects of phase-mismatch terms are estimated. The effects of
      both phase and absorption gratings are obtained. Self-modulation of the recording
      wave is included and unstable solutions are predicted for some regimes. It is
      found that the various regimes have fundamentally different processing
      capabilities.

PMID- 20802618
TI  - Recording of multiple holograms in photopolymer films.
AB  - Multiple images were recorded in DuPont HRF-150 photopolymer as transmission
      holograms by using angle multiplexing. Agreement with Kogelnik's two-wave
      diffraction theory for phase gratings, the time considerations and its effect on
      dynamic range, the necessity of a pre-illumination pulse, and good image quality
      at readout are reported.

PMID- 20802619
TI  - Linear reconstruction of compensated images: theory and experimental results.
AB  - Linear image reconstruction techniques are proposed for postprocessing
      astronomical images measured with compensated imaging systems. Linear techniques
      use averaging to overcome the effects of noise and deconvolution to remove system
      effects. Experimental results from compensated image measurements of four single
      stars and one binary star at visible wavelengths are reported for the first time,
      to our knowledge, and a previously derived analytic expression relating the
      statistics of the compensated optical transfer function to the compensated image
      spectrum signal-to-noise ratio is verified. The performance of deconvolution on a
      bright binary star with angular subtense previously estimated to be 0.52 arcsec
      (2.52 microrad) is demonstrated.

PMID- 20802620
TI  - Wave-front sensing and image deconvolution of solar data.
AB  - High spatial resolution is of the utmost importance for understanding the
      phenomena that are present on the solar surface. Several techniques for wave
      front sensing and image reconstruction have been proposed and used with varying
      degrees of success. The results of a wave-front sensing and imagereconstruction
      experiment that uses phase information obtained by comparing in-focus and out-of
      focus images are presented. The data, a series of snapshots of solar granulation,
      were taken with the Vacuum Tower Telescope at the National Solar Observatory at
      Sacramento Peak. The experiment shows the potential utility of such a technique.
      Advantages and limitations are discussed.

PMID- 20802621
TI  - Theoretical framework for the design of purely real synthetic-discriminant
      function-type correlation filters.
AB  - A general algorithm for synthesizing purely real correlation filters in the
      frequency domain is developed by using the method of Lagrange multipliers. This
      method can be applied to filters that are derived by using linearly constrained
      quadratic minimization. The synthesis of purely real versions of minimum average
      correlation energy filters, minimum-variance synthetic discriminant functions,
      and other synthetic-discriminant-function-type filters is discussed to illustrate
      this approach. Their performance is found to be somewhat less than that of the
      original complex filters but still adequate for practical applications. The main
      advantage of this approach is that optimum purely real filters can be generated
      that are easy to implement in spatial light modulators without holograms and that
      yield the correlation output on the zero-order beam.

PMID- 20802622
TI  - Computational analysis of a holographic optical head configuration.
AB  - The best configuration for holographic optical heads for compact disk players is
      discussed from the viewpoint of considering the misalignment allowance for head
      components. Focus-error and trackingerror signals of the proposed head
      configurations are simulated with a ray-tracing method and by using optical cross
      transfer function theory. The misalignment allowance for the head components,
      such as the objective lens, the holographic optical element, and the
      photodetector, are calculated for several configurations. The misalignment
      allowance is found to increase greatly when the holographic optical element is
      placed in close proximity to the objective lens and then when this assembly is
      moved as a unit.

PMID- 20802623
TI  - Data reliability evaluation of flexible optical disk system using accelerated
      test of dust density.
AB  - The data reliability of a 90-mm flexible optical disk system with a phase-change
      rewritable disk is studied through accelerated tests of dust density for
      fabrication of low-cost, reliable flexible optical disks. A simple dust generator
      composed of a small loud speaker creates an extremely dusty environment in a
      chamber, with a dust density several times higher than in a normal environment.
      These accelerated tests indicate that a flexible optical disk contained in a
      semisealed cartridge will show no change in the number of errors over several
      years in a normal environment.

PMID- 20802625
TI  - Nasa patter.

PMID- 20802624
TI  - Free-space photonic switching architectures based on extended generalized shuffle
      networks.
AB  - A new class of networks that is well suited for free-space photonic switching
      applications is described. These networks are known as extended generalized
      shuffle networks. It is shown that these networks can provide low blocking
      probabilities while requiring low hardware costs. In fact, if sufficient hardware
      is added to these networks, they become strictly nonblocking networks (with
      blocking probabilities equal to zero). The hardware cost of an extended
      generalized shuffle network can be modified to yield any desired blocking
      probability, so cost-effective designs are possible. In addition, it is shown
      that these networks are extremely fault tolerant, and they can also be designed
      to have high system availabilities. Because the networks can use various types of
      interconnections to connect the nodes and because the nodes can have various
      types of functionality, these networks also provide high degrees of flexibility
      that can be used to optimize a free-space photonic design. The design of extended
      generalized shuffle networks based on a particular node type that is easy to
      implement with symmetric self-electro-opticeffect devices is studied.

PMID- 20802626
TI  - Tunable external cavity diode laser that incorporates a polarization half-wave
      plate.
AB  - The threshold current and specttal properties of a grating tuned external cavity
      semiconductor laser are improved by utilizing an intracavity half-wave plate to
      optimize the grating feedback.

PMID- 20802627
TI  - Frequency noise induced by fiber perturbations in a fiber-linked stabilized
      laser.
AB  - The effects of acoustic perturbations on an optical fiber that links a stabilized
      laser to its reference cavity are studied. An extrapolation indicates that 69 dB
      of acoustic noise impinging on a 1-m segment of the 10-m fiber contribute
      frequency noise at the level of 1 Hz/(Hz) ((1/2)) in the 1100- 21 00-Hz band.

PMID- 20802628
TI  - Pulse energy control in Q-switched, diode-pumped solid-state lasers.
AB  - This control system randomly scans a Q-switched diodepumped Nd:YLF laser from
      hertz to kilohertz repetition rates with less than +/-5% (3sigma) pulse-energy
      jitter.

PMID- 20802629
TI  - Midfocus matching: a method for calculating lens positions for a Gaussian beam in
      a two-lens system.
AB  - For the situation in which a specific laser beam waist is required at a certain
      position, we develop a practical method of selecting focal lengths for a
      combination of two lenses and of calculating their positions. The method
      provides, in an easy graphical way, the solution of this two-lens focusing
      problem of Gaussian beams by finding the crossing point of two parametric curves.

PMID- 20802630
TI  - Sun-pumped lasers: revisiting an old problem with nonimaging optics.
AB  - The techniques of nonimaging optics have permitted the production of a world
      record intensity of sunlight, 72 W/mm(2), by using a sapphire concentrator. Such
      an intensity exceeds the intensity of light at the surface of the Sun itself (63
      W/mm(2)) by 15% and may have useful applications in pumping lasers, which require
      high intensities of light to function. The author describes the production of
      high-intensity sunlight and reports its application in generating over 3 W of
      laser power from a 72.5-cm-diameter telescope mirror at an efficiency exceeding
      that typically attained in approaches not involving nonimaging optics.

PMID- 20802631
TI  - Modifying the one-dimensional power-coupling formalism to model a cw Nd:YAG
      laser.
AB  - A lamp-pumped, cw Nd:YAG laser cannot be modeled adequately by the one
      dimensional power-coupling formalism without assuming intensity-dependent cavity
      losses. The source of the intensity dependence has not been determined but may be
      due to absorption saturation in the gain medium or to aperture and beam profile
      effects.

PMID- 20802632
TI  - Unstable resonators with distributed saturable gain and nonuniform reflectivity
      outcouplers in the geometrical optics limit.
AB  - An existing geometrical optics method for calculating the longitudinal and
      transverse dependence of the mode intensities in unstable resonators with sharp
      edged feedbacks mirrors and distributed saturable gain is modified to include the
      nonuniform reflectivity of the outcoupling feedback mirror. Results show that the
      mode extends increasingly outward as the gain increases, so the size of a
      limiting aperture must be chosen with care to prevent unwanted diffraction. An
      attempt to prescribe an arbitrary spatially limited output function of a loaded
      cavity and to find the required mode and reflectivity profiles yields spatially
      unlimited functions.

PMID- 20802633
TI  - Unstable resonators with nonuniform reflectivity outcouplers: geometric theory
      for bare cavities.
AB  - The eigenequation from the geometric theory of unstable resonators with
      nonuniform reflectivity outcouplers is solved by a series method. Either the
      reflectivity profile or the dominant mode can be specified and the other can be
      obtained. A spatially limited output can also be specified, but the resulting
      mode and reflectivity profile are not guaranteed to be spatially limited. This
      problem can be avoided, but a good general method for obtaining all of the
      desired features has not been found.

PMID- 20802634
TI  - Pulsed optical damage threshold of potassium niobate.
AB  - We have determined the optical damage threshold of orthorhombic potassium niobate
      under pulsed laser irradiation for wavelengths of 1054 and 527 nm and pulse
      durations of 700 and 500 ps, respectively. Six uncoated crystals and two crystals
      with antireflection coating were tested. The single-shot damage thresholds varied
      between 4.1 J/cm(2) at 527 nm (lowest value observed) and 26.4 J/cm(2) at 1054 nm
      (the highest value observed). The threshold fluence was found to depend on the
      polarization direction of the incident radiation with respect to the crystal
      axes.

PMID- 20802635
TI  - Simple technique for determining substrate indices of isotropic materials by a
      multisheet Brewster angle measurement.
AB  - When an H-polarized light is incident upon a substrate at the Brewster angle, the
      reflected light becomes zero. Stacking many identical substrates together forms a
      multisheet structure. The valley of this reflected intensity pattern centered at
      the Brewster angle becomes narrower owing to the overlap of these similar
      reflections from many parallel interfaces of air and substrates. Therefore
      measuring the Brewster angle of this multisheet structure leads to an accurate
      determination of the substrate index, which is up to the third decimal place
      (0.00075).

PMID- 20802636
TI  - Source of tunable radiation based on Ti(3+):Al(2)O(3) crystals pumped by a copper
      vapor laser.
AB  - A source of tunable coherent radiation based on the use of Ti(3+):Al(2)O(3)
      crystals pumped by Cu-vapor laser radiation is studied experimentally. This
      source is promising for applications to atmospheric sensing as well as for use in
      applied optics and spectroscopy studies. Energy, kinetic, spectral, and spatial
      characteristics of lasing in nonselective and selective cavities and in the
      master oscillator power amplifier system are measured. Based on the latter scheme
      an experimental model of the source is developed. It permits continuously tunable
      radiation to be obtained in two spectral regions, i.e., within the fundamental
      band from 680 to 980 nm with a maximum average output power of ~2.6 W and in its
      second harmonic range from 340 to 490 nm with a maximum average output power of
      450 mW. The linewidth of the emission is ~2 pm everywhere in the operating
      wavelength ranges, and the beam divergence is close to that of the diffraction.
      The pulse repetition rate is 5 kHz. A further increase in the output power is
      possible.

PMID- 20802637
TI  - Frequency doubling of a Nd:YAG laser using a crystal-cored fiber of an organic 4
      (N,N-dimethylamino)-3-acetamidonitrobenzene.
AB  - Optical second-harmonic generation from a glass-clad fiber with an organic core
      crystal of 4-(N,Ndimethylamino)-3-acetamidonitrobenzene (DAN) is demonstrated.
      Phase matching was due to cerenkov radiation. Linear and nonlinear optical
      properties of DAN, a fabrication technique of a crystal-cored fiber, and a
      focusing method of the generated second-harmonic wave are studied.

PMID- 20802638
TI  - Coupling mechanisms and transfer functions of optical fiber devices.
AB  - Modal-power transfer functions for two basic coupling mechanisms, i.e.,
      scattering coupling and overlap coupling, are derived. Optical fiber devices such
      as fibers or cables, connectors, splices, and power splitters can be
      characterized by modal-power transfer relations based on these transfer
      functions. Experimental results show that the transfer functions are independent
      of launch conditions.

PMID- 20802639
TI  - Polarization controller based on a fiber-recirculating delay line.
AB  - A fiber-optic polarization control device constructed from a recirculating delay
      line is introduced and analyzed. This controller is found to be without a bulk
      optic counterpart and is notably different in design and operation from existing
      fiber polarization controllers. Full control is achieved by varying two
      birefringence terms and a phase delay term. The device is shown to be capable of
      handling arbitrary polarization-state transformations and control. The design
      technique for this system is also fundamentally different from that of previous
      polarization controllers.

PMID- 20802640
TI  - Focusing geometries for constant fluence in infrared multiple-photon
      dissociation.
AB  - Generalized mathematical expressions are presented that describe the fluence
      distribution of a laser beam focused properly into an optically thick gas medium
      so that the axial fluence distribution is made nearly constant. The laser-beam
      focusing parameters are optimized such that they compensate for the decrease in
      pulse energy along the beam axis. Two cases are taken into account for optical
      absorption. These cases are linear and nonlinear absorption, of which the latter
      is often met in infrared multiple-photon dissociation and applied widely to laser
      isotope separation. It is demonstrated that an optimized focusing is effective in
      achieving almost constant axial fluence distribution, thereby maximizing reaction
      yields of a target isotopic component without the loss of isotopic selectivities
      in laser-isotope separation.

PMID- 20802641
TI  - Analysis of laser-assisted chemical etching processes of a pinhole by monitoring
      diffraction patterns of reflected beams.
AB  - The detailed processes of laser-assisted chemical etching are studied by using an
      optical in situ monitoring method. Various Al thin-film specimens are processed
      in aqueous H(3)PO(4) solutions by shining focused Ar(+) laser beams. As etching
      progresses, it is observed in the backreflected laser beam that a concentric
      circular fringe pattern appears and shrinks. The development of the etching
      process is explained by analyzing the diffraction patterns with an etched shape
      function of a Gaussian nature.

PMID- 20802642
TI  - Transmission properties of rectangular hollow waveguides for CO(2) laser light.
AB  - Transmission losses of two types of dielectric-coated rectangular waveguide are
      analyzed theoretically to transmit linearly or circularly polarized CO(2) laser
      light. When ZnS and PbTe are chosen as coating materials, waveguide losses are
      reduced by ~ 1 order of magnitude by increasing each pair of coating materials.
      Phosphor bronze rectangular waveguides with small aspect ratios and various cross
      sections, whose inner walls are coated with a single PbF(2) layer, are fabricated
      by using vacuum-evaporation and assembly techniques. Transmission losses of
      straight and bent waveguides are measured for coherent CO(2) laser light as well
      as for incoherent infrared lights. Straight waveguide losses of 0.1 dB/m
      including a coupling loss from a laser, are obtained at a 10.6-microm wavelength
      for 1-m-long and small-core waveguides.

PMID- 20802643
TI  - Multibeam transmitter for signal dynamic range reduction in incoherent lidar
      systems.
AB  - A multibeam transmitter provides the flexibility to change the overlap function
      and range response function of monostatic incoherent lidar systems. A nearly flat
      range response and a close near-range coverage can be achieved simultaneously,
      even under different atmospheric conditions. Such a significant improvement in
      range response will solve the problem of detector overexposure by near-range
      atmosphere-backscattered radiation (which leads to nonlinear response,
      saturation, or even damage of the detector), and will significantly reduce the
      dynamic range of the detector output signal, thus reducing quantization error of
      the digitizer. Consequently, the accuracy of lidar measurements, especially that
      of differential absorption lidar measurements, will be improved.

PMID- 20802644
TI  - Effects of water-emission anisotropy on multispectral remote sensing at thermal
      wavelengths of ocean temperature and of cirrus clouds.
AB  - The assumption of blackbody emission (emissivity, 1.0) for a calm ocean surface
      can lead to significant underestimates of the sea-surface temperature (SST)
      derived from IR radiometric data. Taking the optical properties of the atmosphere
      as known, we calculate the errors stemming from the blackbody assumption for
      cases of a purely absorbing or a purely scattering atmosphere. It is observed
      that for an absorbing atmosphere the errors in SST are always reduced and are the
      same whether measurements are made from space or at any level in the atmosphere.
      As for atmospheric scattering, the SST errors are slightly reduced when one is
      viewing from large zenith angles but are slightly enhanced when one is viewing
      from the zenith. The inferred optical thickness tau of an absorbing layer can be
      in error under the blackbody assumption by a Deltatau of 0.01-0.08, while the
      inferred optical thickness of a scattering layer can be in error by a larger
      amount, Deltatau of 0.03-0.13. The error Deltatau depends only weakly on the
      actual optical thickness and on the viewing angle, but it is rather sensitive to
      the wavelength of the measurement. In the absence of steep slopes in the wave
      slope distribution, directional emissivities are essentially unchanged by sea
      state when one is viewing from or near the zenith. When one is viewing from
      moderately large zenith angles (such as 507 degrees ), however, the departures in
      the directional emissivities from blackbody emission can be much larger under
      perturbed sea state than under calm conditions.

PMID- 20802645
TI  - Wave-front matching measurement in coherent CO(2) laser-radar.
AB  - Wave-front matching of the local oscillator beam and the signal beam is of vital
      importance in optical heterodyne efficiency. A method for aligning the local
      oscillator beam and the signal beam is described. Mixing efficiency is improved.
      One can directly observe the matching procedure on an oscilloscope.

PMID- 20802646
TI  - Point-spread function associated with underwater imaging through a wavy air-water
      interface: theory and laboratory tank experiment.
AB  - The point-spread function needed for imaging underwater objects is theoretically
      derived and compared with experimental results. The theoretical development is
      based on the emergent-ray model, in which the Gram-Charlier series for the non
      Gaussian probability-density function for emergent angles through a wavy water
      surface was assumed. To arrive at the point-spread model, we used a finite
      element methodology with emergent-ray angular probability distributions as
      fundamental building functions. The model is in good agreement with the
      experiment for downwind conditions. A slight deviation between theory and
      experiment was observed for the crosswind case; this deviation may be caused by
      the possible interaction of standing waves with the original air-ruffled
      capillary waves that were not taken into account in the model.

PMID- 20802647
TI  - Remote probing of a distant turbulent layer using various spatial filtering
      methods.
AB  - A theoretical analysis of short-exposure, spatial power spectra of defocused
      images viewed through a thin scattering layer is given. Information about the
      position of the layer can be recovered from these spectra by using a class of
      quasi-one-dimensional incoherent sources and a spatial filter on the aperture
      plane. The same approach can be used to obtain refractive turbulent profiles with
      high spatial resolution in an extended medium.

PMID- 20802648
TI  - Asymptotic theory for optically thick layers: application to the discrete
      ordinates method.
AB  - Asymptotic expressions for the reflected, transmitted, and internal scattered
      radiation field in optically thick, vertically homogeneous, plane-parallel media
      are derived from first principles by using the discrete ordinates method of
      radiative transfer. Compact matrix equations are derived for computing the escape
      function, diffusion pattern, diffusion exponent, and the reflection function of a
      semi-infinite atmosphere in terms of the matrices, eigenvectors, and eigenvalues
      that occur in the discrete ordinates method. These matrix equations are suitable
      for numerical computations and are valid throughout the full range of single
      scattering albedos. The present formulations are validated by comparing them with
      established methods of radiative transfer.

PMID- 20802649
TI  - Identification and imaging of OH (nu'' = O) and O(2) (nu'' = 6 or 7) in an
      automobile spark-ignition engine using a tunable KrF excimer laser.
AB  - Planar laser-induced predissociative fluorescence is applied to image state
      specific densities of OH and hot O(2) inside an internal-combustion car engine.
      Improved instrumentation is described. It includes better imaging optics and a
      spectrometer that permits desired molecular quantum states to be selected and
      identified in real time. The OH (nu'' = 0) images are cleanly separated from the
      isooctane fuel and they display a thin superequilibrium region at the flame
      front. In contrast, vibrationally excited O(2) (nu'' = 6 or nu'' = 7) is
      uniformly distributed behind the front. Uneven and broken flame fronts are
      commonly observed.

PMID- 20802650
TI  - Ground-based laser radar measurements of satellite vibrations.
AB  - Vibration signatures from the low-power atmospheric compensation (LACE) satellite
      are obtained by using the MIT Lincoln Laboratory Firepond coherent CO(2) laser
      radar facility located in Westford, Mass. The LACE satellite is equipped with IR
      germanium retroreflectors on deployable/retractable booms to enhance ground-based
      IR laser radar measurements of on-orbit boom vibrations. Analysis of pulsed cw
      laser radar measurements of the satellite during and subsequent to boom
      retraction indicates the presence of a complex time-varying model structure. The
      observed vibration spectra include vibration modes not previously predicted.
      These data represent the first observations of satellite vibration modes from a
      ground-based laser radar.

PMID- 20802651
TI  - Three-dimensional computed tomography from interferometric measurements within a
      narrow cone of views.
AB  - A theory is presented and tested for recovering a fluid property from
      measurements of its projections. Viewing comes as small as 10 degrees are
      evaluated, and the only assumption is that the property is space limited. The
      results of applying the theory to numerical and actual interferograms of a
      spherical discontinuity of refractive index are presented. The theory was
      developed to test the practicality and limits of using three-dimensional computed
      tomography to process optical diagnostic data for internal fluid dynamics.

PMID- 20802652
TI  - Long fiber-optic remote Raman probe for detection and identification of weak
      scatterers.
AB  - A long-length fiber-optic remote Raman probe that can detect materials (e.g.,
      Fe(2)O(3)) that are weak Raman scatterers is described. The 100-m-long probe
      consists of one excitation and one collection fiber and accessory optics and is
      <3 mm in diameter. We used special filters to solve the problems of Raman
      scattering and luminescence generated in the silica excitation and collection
      fibers and a liquid-nitrogencooled charge-coupled detector to analyze weak Raman
      signals.

PMID- 20802653
TI  - Differential correction technique for removing common errors in gas filter
      radiometer measurements.
AB  - The Measurement of Air Pollution from Satellites (MAPS) gas filter radiometer
      experiment was designed to measure CO mixing ratios in the Earth's atmosphere.
      MAPS also measures N(2)O to provide a reference channel for the atmospheric
      emitting temperature and to detect the presence of clouds. In this paper we
      formulate equations to correct the radiometric signals based on the spatial and
      temporal uniformity of the N(2)O mixing ratio in the atmosphere. Results of an
      error study demonstrate that these equations reduce the error in inferred CO
      mixing ratios. Subsequent application of the technique to the MAPS 1984 data set
      decreases the error in the frequency distribution of mixing ratios and increases
      the number of usable data points.

PMID- 20802654
TI  - Patents.
AB  - 5,011,254; 5,040,872; 5,052,780; 5,066,127; 5,067,801; 5,069,548; 5,069,551;
      5,071,207; 5,070,874; 5,071,209; 5,071,239; 5,072,104; 5,073,007; 5,073,016;
      5,073,108; 5,074,629; 5,073,705; 5,074,645; 5,076,655.

PMID- 20802655
TI  - Photon tunneling microscopy of diamond-turned surfaces.
AB  - The photon tunneling microscope's high-resolution, large-field, and real-time
      three-dimensional display with profilometry and continuously variable perspective
      make it a powerful tool for analysis of diamond-turned surfaces.

PMID- 20802656
TI  - Spectral spread function of a double-pass parabolized Ebert monochromator.
AB  - We have studied the influence of the residual coma and the width of the
      intermediate slit on the spectral spread function of a double-pass parabolized
      Ebert monochromator.

PMID- 20802657
TI  - Surface profiling by means of double spectral modulation.
AB  - Double modulation-in frequency and intensity-of the power spectral distribution
      of a light beam is proposed for interferometric profilometry. The procedure is
      based on two facts: (1) the continuous spectrum of a light source is frequency
      modulated by the path difference in an interferometric device, (2) the continuous
      spectrum of a light source is intensity modulated by the transparency of an
      object placed in the exit plane of a spectroscopic device. Both procedures can be
      used to measure the profile of a surface with high precision. Moreover, phase
      shifting is automatically performed by the continuous wavelength variation along
      the spectrum, so that no piezoelectric transducers are necessary. The method is
      adaptable for the analysis of remote surfaces through optical fibers.

PMID- 20802659
TI  - Improving the linearity of the Michelson interferometric angular measurement by a
      parameter compensation method.
AB  - A parameter compensation method is developed to improve the linearity of the
      Michelson interferometric angular measurement. The formulas for the exact
      calculation of the parameters are presented; different cases are discussed. By
      introducing a weight function in the calculation, we can change the distribution
      of the linearity over the whole range of measurement. The theoretical analysis
      and the experimental results show that this method greatly improves the linearity
      of the measurement even for a large range of measurement.

PMID- 20802658
TI  - Calibration of silicon photodiodes by photoacoustics.
AB  - We present a new approach to the calibration of silicon photodiodes that are used
      for light (radiometric) power measurements. We describe the photoacoustic method
      for the determination of internal quantum efficiency and absolute spectral
      response of silicon photodiodes in the photovoltaic short-circuit mode.
      Measurements were taken for the different structures of silicon photodiodes.

PMID- 20802660
TI  - Wavelength-dependent sensitivity limitations affecting low light level Michelson
      stellar interferometry.
AB  - The use of multiple aperture ground interferometers to measure directly the
      diameters of resolvable stars or to determine the separations and position angles
      of compact multiple star systems is well established in the literature. The
      general utility of this technique for producing catalogs of such observations,
      however, is fundamentally constrained by such noise processes as shot noise,
      detector dark current, and background radiation, all of which limit
      interferometric sensitivity. We review the various sensitivity limitations
      affecting low light level Michelson amplitude interferometry for these
      applications and calculate the wavelength-dependent detection thresholds as
      expressed in limiting stellar visual magnitudes that can be so achieved.

PMID- 20802661
TI  - Infrared optical constants of polycrystalline boron nitride.
AB  - Effective optical constants of boron nitride have been determined at CO(2) laser
      wavelengths. Waveguiding losses are evaluated to be 3 x 10(-4) cm(-1) for a 2-mm
      inner-diameter guide showing the suitability of boron nitride for waveguide laser
      construction.

PMID- 20802662
TI  - Staircase lens: a binary and diffractive field curvature corrector.
AB  - The optical characteristics of a family of diffractive lenses, called staircase
      lenses, are discussed. These lenses contribute no optical power and the fourth
      order wave aberrations Petzval field curvature, distortion, and chromatic
      aberrations when collimated illumination is used. A diamond-turned staircase lens
      comprising 150 steps was manufactured. The test results verify the generation of
      field curvature and longitudinal chromatic aberration.

PMID- 20802663
TI  - Autocorrelation functions from optical scattering for one-dimensionally rough
      surfaces.
AB  - The relationship between the height autocorrelation function of a one
      dimensionally rough surface and the Fourier transform of the intensity
      distribution of the light scattered by that surface is tested experimentally. The
      theory is derived by using the Fraunhofer approximation, without recourse to the
      inconsistent Kirchhoff boundary conditions. In spite of the limitations imposed
      by the approximations used, the results obtained from optical data agree well
      with those obtained from stylus data, even for an autocorrelation length as small
      as the optical wavelength. However, this method should be limited to surfaces
      with rms roughness smaller than approximately 0.14 times the wavelength of light.

PMID- 20802664
TI  - Automatic deformation analysis by a TV speckle interferometer using a laser
      diode.
AB  - A phase-shifting TV speckle interferometer is developed by using the frequency
      modulation capability of a laser diode and is applied to automatic deformation
      measurements. Temperature modulation is used for generating the frequency shift
      of a laser diode. We store four speckle interferograms with relative phase
      differences of pi/2 in a frame grabber by monitoring a phase-shift signal, which
      is obtained by integrating the fringe intensity over a local window. The optimum
      size of the local window is examined experimentally. Then, the optimum processing
      conditions for reducing the speckle noise in interferograms,including an
      averaging window size, are found. Experimental results of the automatic
      deformation analysis indicate a displacement accuracy of better than lambda/30.

PMID- 20802665
TI  - Detection of thin a-Si:H antireflective coatings on oxidized c-Si by resonant
      detected spectroscopic ellipsometry.
AB  - The cleaning procedures applied in the wafer processing of thin a-Si:H overlayers
      have been monitored by spectroscopic ellipsometry. By selecting a suitable sample
      configuration and exploiting a tunable angle of incidence, we show that
      spectroscopic ellipsometry is extremely sensitive to small modifications at the
      vacuum-a-Si:H interface induced by the cleaning procedures. Experimental results
      are presented on the characterization of thin (3-12-nm) a-Si:H films on top of
      thermally oxidized crystalline silicon. Submonolayer sensitivity of the
      ellipsometric measurement to changes in a-Si:H film thickness is shown.

PMID- 20802666
TI  - Thermal conductivities of thin, sputtered optical films.
AB  - The normal component of thin-film thermal conductivity has been measured for the
      first time, to the best of our knowledge, for several advanced sputtered optical
      materials. Included are data for single layers of boron nitride, silicon aluminum
      nitride, silicon aluminum oxynitride, silicon carbide, and for dielectricenhanced
      metal reflectors of the form Al(SiO(2)/Si(3)N(4))(n) and Al(Al(2)O(3)/AlN)(n).
      Sputtered films of more conventional materials such as SiO(2), Al(2)O(3),
      Ta(2)O(5), Ti, and Si have also been measured. The data show that thin-film
      thermal conductivities are typically 10 to 100 times lower than conductivities
      for the same materials in bulk form. Structural disorder in the amorphous or fine
      grained films appears to account for most of the conductivity difference.
      Conclusive evidence for a film-substrate interface contribution is presented.

PMID- 20802667
TI  - Optical properties of a metal island film close to a smooth metal surface.
AB  - Bright colors have been observed when a metal island film is deposited on top of
      a silver mirror with a separating quartz layer. For spacer layer thicknesses that
      are varied from 0 to 140 nm, the visual appearance changes from blue/black to a
      series of brilliant spectrumlike colors. The sequence is repeated similarly for
      higher interlayer thicknesses. The phenomenon is analyzed in terms of a
      stratified medium theory by using TEM data and an electromagnetic model for the
      optical constants of the metal island film. For island films with a sufficiently
      high absorbance (> 0.35), the spectra are characterized by two sharp minima where
      the reflectivity drops to values below l0(-3). The observed thickness dependence
      is analyzed in terms of a complex combination of the phase shifts caused by the
      island film, the spacer, and the relevant interfaces.

PMID- 20802668
TI  - Design philosophy for progressive addition lenses.
AB  - The design principles of progressive surfaces are discussed in a historic review.
      New aspects on the judgment of the wearing properties of progressive power lenses
      are shown that are based on empirically evaluated data for monocular and
      binocular visual functions.

PMID- 20802669
TI  - Figure of merit of liquid-crystal materials for optically addressed spatial
      modulators.
AB  - A new figure of merit appropriate for optically addressed liquid-crystal spatial
      light modulators is derived. This figure of merit takes into account the change
      of phase retardation and switching time of a deformed liquid-crystal layer. The
      figure of merit is used in determining the optimal mix of polar and weak-polar
      components in the liquid-crystal layer.

PMID- 20802670
TI  - Temporal averaging of phase measurements in the presence of spurious phase drift:
      application to phase-stepped real-time holographic interferometry.
AB  - A technique that compensates for low spatial frequency spurious phase changes
      during an interference experiment is developed; it permits temporal averaging of
      multiple phase measurements, made before and after object displacement. The
      method is tested with phase-stepped real-time holographic interferometry applied
      to cantilever bending of a piezoelectric bimorph ceramic. Results indicate that
      temporal averaging of the corrected data significantly reduces the white noise in
      a phase measurement without incurring systematic errors or sacrificing spatial
      resolution. White noise is reduced from 3 degrees to less than 1 degrees
      (lambda/360) using these methods.

PMID- 20802671
TI  - Ray-matrix approach for diffractive optics.
AB  - Ray matrices are a powerful tool for the analysis of optical systems. This
      technique is modified to include a diffractive optical element within the optical
      system. Several research applications are discussed, including optical Fourier
      transforms and imaging with diffractive optical elements.

PMID- 20802672
TI  - Optical expanders with applications in optical computing.
AB  - An optical system called the optical expander is described and investigated. The
      optical expander electro-optically expands an optical Boolean pattern encoded in
      d bits into an optical pattern of size N bits. It is assumed that d is equal to c
      log(2)N for some constant c, and each expanded pattern is orthogonal to the
      others. Two different architectures to implement the optical expander are
      described: one uses an optical matrix-vector multiplier and an array of N
      threshold devices; the other uses log(2)N novel reflection-transmission switching
      cells. These architectures are analyzed in terms of size, energy requirement, and
      speed. The optical expander described utilizes high-speed and high-space
      bandwidth-product connections that are provided by optical beams in three
      dimensions. Potential applications, holographic memory, and message routing
      systems are also discussed.

PMID- 20802673
TI  - Digital optical cellular image processor (DOCIP): experimental implementation.
AB  - We demonstrate experimentally the concept of the digital optical cellular image
      processor architecture by implementing one processing element of a prototype
      optical computer that includes a 54-gate processor, an instruction decoder, and
      electronic input-output interfaces. The processor consists of a twodimensional (2
      D) array of 54 optical logic gates implemented by use of a liquid-crystal light
      valve and a 2-D array of 53 subholograms to provide interconnections between
      gates. The interconnection hologram is fabricated by a computer-controlled
      optical system.

PMID- 20802674
TI  - Picosecond optical correlation using dynamic holography in polyacetylene.
AB  - An image-processing system based on four-wave mixing in a film of polyacetylene
      less than 100 nm thick is demonstrated with a 1-ps processing cycle time. Image
      phase conjugation and cross correlation are performed with a resolution space
      bandwidth product of 0.68 x 10(5) (equivalent to 261 x 261 pixels) in the phase
      conjugate image. The light source was amplified optical pulses from a colliding
      pulse mode-locked dye laser at a wavelength of 625 nm.

PMID- 20802675
TI  - Sidelobe reduction in optical signal processing.
AB  - A general procedure is introduced for sidelobe and noise reduction in optical or
      digital signal processing. Specific examples of sidelobe reduction in imaging are
      presented. It is demonstrated that the new method provides superior spatial
      resolution to previously proposed sidelobe-reduction techniques.

PMID- 20802676
TI  - Optical pattern recognition using a synthetic discriminant amplitude-compensated
      matched filter.
AB  - A technique for optical pattern recognition using an amplitude-compensated
      matched filter is presented. With the synthetic discriminant function in a
      matched spatial filtering application an iterative technique is employed to first
      obtain the synthetic discriminant functions for the phase-only matched filter and
      then is extended to the amplitude-compensated matched filter. Computer simulation
      shows that the suggested spatial filter has a high signal-to-noise ratio and good
      Horner efficiency, and it is more sensitive to changes in the input image.

PMID- 20802677
TI  - Motionless-head parallel readout optical-disk system.
AB  - The design, analysis, and feasibility of a novel motionless-head parallel readout
      optical-disk system are presented. The system is designed to read data blocks
      distributed radially on the disk's active surface, and it has the unique
      advantage that no mechanical motion of the head is required for fast access,
      focusing, or tracking. Data access is achieved solely through the disk rotation,
      and the entire memory can be read in one rotation. In principle, this permits a
      data rate of up to 1 Gbyte/s. The data blocks are one-dimensional Fourier
      transform computer-generated holograms, each reconstructing one column of a two
      dimensional output image. Owing to the information redundancy and shift
      invariance properties of Fourier-transform holograms, tracking and focusing servo
      requirements are eliminated. A holographic encoding method is developed to
      produce high signal-to-noise ratio reconstructions and to reduce significantly
      the radial alignment requirements of the recorded data bits. The optical readout
      system consists of only three cylindrical lenses. Two of these may be replaced by
      a single hybrid diffractive-refractive optical element for easier system
      alignment and better optical performance, i.e., reduced aberrations and improved
      resolution. The throughputs and retrieval times of this parallel readout optical
      disk system make it well suited to a variety of parallel computing architectures,
      including a high-performance optoelectronic associative memory [Proc. Soc. Photo
      Opt. Instrum. Eng. 1347, 86 (1990)].

PMID- 20802678
TI  - Pulsed lasers in speckle photography: error owing to pulse width.
AB  - The effect of the pulse width of a pulsed laser in the studies of speckle
      velocimetry and transient vibration analysis is discussed. Because of the motion
      of the object during an exposure, a sine function is obtained by using the
      pointwise filtering method. This function modulates the halo along with the
      Young's fringes. It is shown that for high object velocities the sinc function
      modifies the halo distribution; as a result, the error in calculating the fringe
      position increases. An aperture geometry for which the autocorrelation halo is
      made constant in certain regions is proposed in which the intensity variation in
      this region is the result of the modulating sinc function only. A closed-form
      solution for the shift in the position of the fringes in this region is obtained.
      Experimental results of the simulation are presented.

PMID- 20802679
TI  - Determination of the mutual coherence function and determination of the point
      spread function in a transversely and longitudinally inhomogeneous aero-optic
      turbulence layer.
AB  - The mutual coherence function (MCF) of strong-fluctuation theory as a result of
      optical energy passing through a transversely and longitudinally inhomogeneous
      aero-optic turbulent layer is studied. Solutions for the MCF equation are
      determined by decomposing the MCF solution into coherent and incoherent parts and
      by solving separately the equations that result from this decomposition. The MCF
      equations for an arbitrary three-dimensional inhomogeneous layer are presented. A
      simplified version of these equations for the case in which the turbulence
      inhomogeneity is longitudinally inhomogeneous and is transversely inhomogeneous
      in one dimension is also presented. A numerical method for solving the parabolic
      MCF equations by the Lax-Wendroff explicit finite-difference algorithm is given,
      and numerical examples of the MCF solution for three different inhomogeneous aero
      optic layers are discussed. Equations to relate the point-spread function, the
      optical transfer function, and image formation to the MCF of an inhomogeneous
      aero-optic turbulence layer are derived. An approximate MCF Fourier integral
      solution is presented and compared with the exact finite-difference solution. A
      formula to estimate the validity of the approximate integral solution is given.

PMID- 20802680
TI  - Computer-aided speckle interferometry using spectral amplitude fringes.
AB  - A fully automatic speckle metrology technique is developed. Two speckle patterns
      of a specimen, one before and one after the specimen deformation, are captured by
      a video camera. An equivalent double-exposure speckle pattern is obtained by
      superimposing the two digital images. The superimposed speckle pattern is then
      segmented into a series of small subimages. For each subimage a fast-Fourier
      transform is applied and a computer-generated Young's fringe pattern is obtained.
      The fringe pattern, which characterizes the local displacement vector, is
      analyzed by a second fast-Fourier transform. The local displacement vector is
      determined by a cardinal interpolation and a crest searching around a signal peak
      in the second spectral domain. An artificial rigid shift between the two images
      is introduced in the cases of extremely large or small displacements. From
      analysis of all subimage pairs of the whole superimposed speckle pattern a
      complete two-dimensional displacement field is deduced. Experimental results
      using laser as well as white-light speckle patterns are demonstrated.

PMID- 20802681
TI  - Sensitive detection of acetylene absorption in the visible by using a stabilized
      AlGaAs diode laser.
AB  - Overtone transitions of C(2)H(2) at ~ 789 nm are investigated by means of an
      AlGaAs laser operating in an external optical cavity configuration. Relative
      amplitude noise is of a few parts in 10(6) (ppm) and permits an absorption
      detection limit of 0.2 ppm/km. Self-broadening and air broadening is measured for
      two components of the observed band [P(11) at 12646.966 and R(5) at 12688.699 cm(
      1)].

PMID- 20802682
TI  - Collision-induced absorption in the fundamental band of N(2): temperature
      dependence of the absorption for N(2)-N(2) and N(2)-O(2) pairs.
AB  - The collision-induced absorption fundamental band of N(2) has been investigated
      in the 2100-2600 cm(-1) spectral region. Laboratory measurements have been
      undertaken over the temperature range 193-297 K. Binary-absorption coefficients
      for N(2) absorption induced by collisions with N(2) and O(2) are reported and
      compared with N(2) temperature-dependent continua from atmospheric measurements.

PMID- 20802683
TI  - Mode-hop suppression of Littrow grating-tuned lasers.
AB  - Mode-hop suppression in a tunable laser employing a Littrow grating can be
      obtained through a simultaneous sweep of the Littrow grating angle and cavity
      length. The simplest way to obtain such coupled movements is to rotate the
      Littrow grating about a particular axis: We show theoretically and experimentally
      that it is necessary to improve the formalism used in previous calculations to
      treat the problem correctly. The current model explains the different choices
      made in previous studies and gives the optimal rotation point and mechanical
      tolerances to obtain a maximal continuous tuning range. It has been successfully
      tested experimentally.

PMID- 20802684
TI  - Long-pulse excimer laser with a variable reflectivity mirror resonator.
AB  - The performance of a 1-J XeCl excimer laser with a variable reflectivity mirror
      unstable resonator optical cavity is described. The output beam exhibits a flat
      profile in the near field and a far-field energy distribution with approximately
      63% of the energy contained within an angle of 39 microrad (1/e(2) spot size).

PMID- 20802685
TI  - Effects of thermally induced birefringence in high-output-power electro-optically
      Q-switched Nd:YAG lasers and their compensation.
AB  - We show that thermally induced birefringence in an electro-optical crystal can
      play an important role in Q-switched Nd:YAG lasers with a high average power
      output. A compensation of the thermal effects in both active-element and electro
      optical crystals is achieved by employing two identical Pockels cells instead of
      one, with a pi/2 polarization rotator between them in the so-called ring
      modulator. Experiments that are carried out show that undesirable
      thermopolarization effects are essentially eliminated by using this new optical
      configuration. A detailed description in terms of Jones matrices of the
      properties of the proposed resonator is also included.

PMID- 20802686
TI  - Self-mode locking in a Q-switched erbium-doped fiber laser.
AB  - Stable and efficient self-mode locking in a Q-switched highly doped erbium fiber
      laser has been demonstrated. The proposed mechanism of the pulse formation based
      on self-phase modulation agrees well with the observed pulse characteristics.

PMID- 20802687
TI  - Dependence of output near-field beam profile on launching conditions in graded
      index fibers used in delivery systems for Nd:YAG lasers.
AB  - For graded-index optical fibers of a few meters in length and of large core
      diameter, which are typical of those used in beam-delivery systems for high-power
      Nd:YAG lasers, it is shown that the near-field profile of the output beam is a
      strong function of the launch conditions and laser-beam characteristics. The
      output profile depends on the input spot size and its alignment relative to the
      fiber axis as well as on the dependence of the beam divergence on the position
      within the input spot. A theoretical model has been developed to demonstrate how
      the output profile depends on the distribution of guided power between meridional
      modes and groups of skew modes, which are excited by a particular launch
      condition. The predictions of the theoretical model are consistent with the
      experiment.

PMID- 20802688
TI  - Fiber full-polarization-state controller.
AB  - A fiber full-polarization-state controller made by applying variable axial
      strains to both ends of a section of properly central-twisted high linearly
      birefringent fiber is proposed and thoroughly studied. The equations for
      polarization control are extremely simple. Experimental results are in good
      agreement with theoretical predictions.

PMID- 20802689
TI  - Dispersion compensation for an integrated optic grating coupler utilizing a
      transmission volume hologram.
AB  - In this paper we show the analysis and experimental results of using a volume
      holographic grating to increase the wavelength bandwidth over which light is
      coupled into a thin-film optical waveguide. Partial matching of the dispersion
      relationships of a hologram fabricated in dichromated gelatin with a
      waveguide/grating coupler etched in glass, show an increase in the full-width
      half-maximum wavelength (FWHM) bandwidth from approximately 0.25 nm to greater
      than 5 nm.

PMID- 20802690
TI  - Analytical solution for a linearly graded-index-profile planar waveguide.
AB  - An analytical solution is presented for the TE modes of a planar waveguide
      structure comprising a high-index guiding layer and a buried layer with a profile
      such that the square of the index varies linearly and matches the substrate and
      high-index guiding layer. The electric-field profiles and the dispersion relation
      are obtained and discussed, and a solution by the WKB method is compared.

PMID- 20802691
TI  - Optical waveguides fabricated by ion implantation of Si(+) and N(+) in SiO(2): a
      Raman investigation.
AB  - We report an investigation of optical waveguides that are fabricated by
      successive ion implantations at different energies of Si(+) or N(+) ions into
      SiO(2) thermally grown on (100) Si substrates. Implantations of both the species
      result in optical waveguides that sustain propagation over the 5-cm length of the
      sample. Loss coefficients for the waveguides are measured by using Raman
      spectroscopy and are compared with the values obtained in the usual manner by
      collecting elastically scattered light. A typical loss determined by the Raman
      technique was 3.2 dB/cm for the Si-implanted waveguide. Raman data that are
      obtained in the waveguided configuration show a contribution to loss from
      luminescence. The luminescence signal is found to be modulated by an interference
      between the directly scattered radiation from the waveguide region and that
      reflected from the Si-SiO(2) interface. Rapid thermal annealing is found to
      reduce the intensity of the luminescence and thus lower the value of the loss
      coefficient. The lowest loss obtained for the Si-implanted samples is 2.7 dB/cm
      and 3 dB/cm for the N(+)-implanted sample.

PMID- 20802692
TI  - Double V-groove ridge waveguides on a silicon substrate.
AB  - A new design for fabricating low-loss ridge waveguides by anisotropically etching
      two parallel V-grooves on a silicon substrate is proposed and demonstrated.
      Polymethyl methacrylate is used as the waveguide medium, with silicon dioxide and
      air as the lower and upper cladding, respectively. Because of the smooth
      sidewalls of the ridge structure, transverse confinement within the double V
      groove ridge waveguide, with scattering losses of ~ 1.0 dB/cm are observed.

PMID- 20802693
TI  - Thermally induced birefringence and stress in poly(methyl methacrylate)
      waveguides on oxidized silicon substrates.
AB  - A thermally induced birefringence in a poly(methyl methacrylate) waveguide has
      been observed. From polarization measurements made at the output of a waveguide
      in the range 20-60 degrees C, a value for Delta(n(TE) - n(TM))/DeltaT of 1.1 x
      10(-6) degrees C(-1) has been calculated. After waveguide preparation the
      underlying substrate was found to have a bow. By measuring changes in the bow
      caused by temperature in the range 20-60 degrees , we have calculated a value for
      the change in stress in the polymethyl methacrylate film of 0.18 MPa/ degrees C.
      By relating polarization to stress, changes in stress as small as 90 kPa can be
      measured.

PMID- 20802694
TI  - Differential optical absorption spectroscopy (DOAS) system for urban atmospheric
      pollution monitoring.
AB  - We describe a fully computer-controlled differential optical absorption
      spectroscopy system for atmospheric air pollution monitoring. A receiving optical
      telescope can sequentially tune in to light beams from a number of distant high
      pressure Xe lamp light sources to cover the area of a medium-sized city. A beam
      finding servosystem and automatic gain control permit unattended long-time
      monitoring. Using an astronomical code, we can also search and track celestial
      sources. Selected wavelength regions are rapidly and repetitively swept by a
      monochromator to sensitively record the atmospheric absorption spectrum while
      avoiding the detrimental effects of atmospheric turbulence. By computer fitting
      to stored laboratory spectra, we can evaluate the path-averaged concentration of
      a number of important pollutants such as NO(2), SO(2), and O(3). A measurement of
      NH(3) and NO close to the UV limit is also demonstrated.

PMID- 20802695
TI  - Blue-green laser-induced fluorescence from intact leaves: actinic light
      sensitivity and subcellular origins.
AB  - Remote sensing of the health status of vegetation should be possible by using UV
      laser-induced fluorescence; nevertheless, the molecular origin of the leaf blue
      green fluorescence emission is still unknown. In order to investigate possible
      relations of this fluorescence to the photosynthetic apparatus, we looked for its
      intensity changes after the addition of actinic light. The lack of any changes
      outside the chlorophyll fluorescence bands (Kautsky effect) was further
      investigated by collecting spectra from cell, protoplast, and chloroplast
      suspensions. These spectra led us to ascribe most of the blue-green laser-induced
      fluorescence that is detectable on a leaf by UV laser excitation to
      extrachloroplastic compartments. In active chloroplast suspensions blue
      fluorescence from photosynthetically reduced nicotinamide adenine dinucleotide
      phosphate (NADPH) has been detected and should be characterized by time-resolved
      fluorescence techniques.

PMID- 20802696
TI  - Deltak Lidar sensing of surface waves in a wave tank.
AB  - The Deltak lidar remote-sensing method is used in a laboratory wave tank
      demonstration to measure the frequency of surface waves as a function of their
      wavelength. The results clearly demonstrate the ability of the Deltak lidar
      method to detect a single surface wave among an ensemble of waves present on the
      surface with a signal-to-noise ratio that agrees with the theory.

PMID- 20802698
TI  - Patents.
AB  - 4,963,017; 4,974,946; 4,984,855; 4,996,441; 5,002,347; 5,008,908; 5,009,486;
      5,018,861; 5,020,905; 5,031,199; 5,031,993; 5,035,478; 5,044,750; 5,048,966;
      5,049,753; 5,050,965; 5,050,966; 5,051,577; 5,056,895; 5,058,968; 5,061,027;
      5,061,046; 5,062,694; 5,067,788.

PMID- 20802697
TI  - UV-B Robertson-Berger meter characterization and field calibration.
AB  - The New Zealand Meteorological Service has used a Robertson-Berger meter (RB
      meter) to monitor solar UV-B radiation for the past decade. The radiometric
      properties of the instrument have been analyzed and agree with the standard
      values published by Berger. A detailed theoretical treatment of the RB meter
      response that fully accounts for its cosine response is presented. Field
      measurements made with the RB meter and with a double monochromator spectral
      radiometer were used to validate the theoretical model and to derive a
      calibration for the RB meter. Only cloud-free data were considered so that the
      downward radiation field at the surface could be modeled as the sum of direct
      solar and isotropic diffuse components. The imperfect cosine responses of both
      instruments were modeled. A RB meter count was found to equate to 0.25 +/- 0.02
      Jm(-2) referenced to 300-nm radiation at vertical incidence.

PMID- 20802699
TI  - Changes in the optical properties (at 632.8 nm) of slowly heated myocardium.
AB  - The three transport equation optical properties, the absorption coefficient, the
      scattering coefficient, and the average cosine of the scattering angle, or
      anisotropy factor have been measured (at 632.8 nm) for canine myocardium after it
      is heated in a water bath at room temperature and at 37-75 degrees C for 1000 s.
      The measurement system was a double integrating sphere with collimated light and
      utilized the adding-doubling solution to the equation of radiative transfer. The
      absorption coefficient (room temperature control, 2.0 +/- 0.4 cm(-1)) began to
      increase and the anisotropy factor (room temperature control, 0.93 +/- 0.02) to
      decrease at above 45 degrees C. At 75 degrees C the changes were significant at
      the p < 0.0005 level (absorption, 4.5 +/- 1.3 cm(-1); anisotropy, 0.78 +/- 0.05).
      There was no significant change in the scattering coefficient (room temperature
      controls, 161 +/- 33 cm(-1)).

PMID- 20802700
TI  - Time-resolved optical tomography.
AB  - We have obtained transaxial slice images of a cylindrical object containing a
      highly scattering, low-absorbing solution by using picosecond pulses of visible
      light. Embedded in the solution was an assortment of six glass tubes containing
      different concentrations of absorbing dye. We reconstructed images
      tomographically from projections generated by using light transmitted through the
      object with theshortest flight times.

PMID- 20802701
TI  - Spatial localization of absorbing bodies by interfering diffusive photon-density
      waves.
AB  - The use of the destructive interference of diffusive photon-density waves for the
      localization of an absorbing (and scattering) body in a scattering medium was
      studied. The objectives of this approach in the reflectance mode were as follows:
      first, to reduce sensitivity to absorption features occurring in superficial
      layers while sensitivity to bodies lying deeper is maintained; second, to
      establish a confined depth region of maximum sensitivity in which the distance of
      an absorbing body could be determined through phase measurement. Intensity and
      phase data were acquired with a modified frequency-domain spectrometer at
      modulation frequencies up to 600 MHz as an absorbing body was moved in three
      dimensions. The experimental results are compared with simulations based on a
      numerical solution of a time-dependent photon-diffusion equation.

PMID- 20802702
TI  - Infrared measurements of sapphire fibers for medical applications.
AB  - Infrared transmission losses as low as 8 dB/km at 1060 nm and damage a threshold
      above 1.3 kJ/cm(2) at 2940 nm have been measured for experimental single-crystal
      sapphire fibers.

PMID- 20802703
TI  - Modeling the effect of wavelength on the pulsed dye laser treatment of port wine
      stains.
AB  - To determine the influence of wavelength on the depth of vascular injury in port
      wine stains following pulsed dye laser treatment, we calculated fluence rates at
      wavelengths varying from 415 to 590 nm in a two-layer Monte Carlo model
      representing the epidermis and the dermis. Calculations were made for four
      different volumetric fractions of blood in the dermis: 0%, 1%, 5%, and 10%. The
      depth of the selective vascular injury was determined to be the depth at which
      the rate of temperature rise at some point within the vessel just equals that at
      the epidermal-dermal junction. This was maximal between 577 and 590 nm with the
      maximum shifted toward 590 nm for a greater dermal blood content and for larger
      vessels. The effect of greater epidermal pigmentation was not only to reduce the
      depth of vascular injury but to shift slightly the wavelength of the maximum
      vascular injury to a shorter wavelength.

PMID- 20802704
TI  - Double-integrating-sphere system for measuring the optical properties of tissue.
AB  - A system is described and evaluated for the simultaneous measurement of the
      intrinsic optical properties of tissue: the scattering coefficient, the
      absorption coefficient, and the anisotropy factor. This system synthesizes the
      theory of two integrating spheres and an intervening scattering sample with the
      inverse adding-doubling algorithm, which employs the adding-doubling solution of
      the radiative transfer equation to determine the optical properties from the
      measurement of the light flux within each sphere and of the unscattered
      transmission. The optical properties may be determined simultaneously, which
      allows for measurements to be made while the sample undergoes heating, chemical
      change, or some otherexternal stimulus. An experimental validation of the system
      with tissue phantoms resulted in the determination of the optical properties with
      a < 5% deviation when the optical density was between 1 and 10 and the albedo was
      between 0.4 and 0.95.

PMID- 20802705
TI  - Theoretical model for the scattering of light by dentin and comparison with
      measurements.
AB  - A theoretical model of the scattering of light by dentin is presented. The model
      that results is a superposition of several scattering contributions, i.e.,
      scattering by mineral crystals, collagen fibrils, and dentinal tubules. These
      tubules are oriented so that they cause an asymmetrical scattering process. The
      angular intensity functions are calculated for planes that are parallel or
      perpendicular to the plane of the tubules. The shape of the measured intensity
      function in the plane perpendicular to the tubules and the values of the
      scattering coefficient can be explained by the model that we present.

PMID- 20802706
TI  - Pulsed lasers in particle detection and sizing.
AB  - We demonstrate the feasibility of using a pulsed copper vapor laser in particle
      detection and sizing, Despite the low-duty cycle of these lasers (0.025%), the
      forward scatter of light from 5-microm latex spheres has been detected.

PMID- 20802707
TI  - Spectral dependence of temporal point spread functions in human tissues.
AB  - We have determined the spectral dependence of the temporal point spread functions
      of human tissues experimentally between 740 and 840 nm in transmittance
      measurements on the adult head, forearm, and calf (in vivo) and the infant head
      (post mortem) by using picosecond laser pulses and a streak camera detector. Two
      parameters are extracted from the temporal point spread function; the
      differential path-length factor (DPF), calculated from the mean time, and the
      slope of the logarithmic intensity decay. In all tissues the DPF and the
      logarithmic slope show a reciprocal relationship and exhibit characteristics of
      the absorption spectra of hemoglobin. The DPF falls with increasing wavelength,
      the variation being typically 12%, while the logarithmic slope increases with
      wavelength. A quantitative analysis of the logarithmic slope spectrum
      significantly underestimated expected tissue chromophore concentrations. The
      absolute magnitudes of the DPF showed considerable intersubject variation, but
      the variation with wavelength was consistent and thus may be used in the
      correction of tissue attenuation spectra.

PMID- 20802708
TI  - Condensed Monte Carlo simulations for the description of light transport.
AB  - A novel method, condensed Monte Carlo simulation, is presented that applies the
      results of a single Monte Carlo simulation for a given albedo
      micro(s)/(micro(alpha) & micro(s)) to obtaining results for other albedos;
      micro(s) and micro(alpha), are the scattering and absorption coefficients,
      respectively. The method requires only the storage of the number of interactions
      of each photon with the medium. The reflectance and transmittance of turbid slabs
      can thus be found from a limited number of condensed Monte Carlo simulations. We
      can use an inversion procedure to obtain the absorption and scattering
      coefficients from the total reflectance and total transmittance of slabs.
      Remitted photon densities from a semi-infinite medium as a function of the
      distance between the light source and the detector for all albedos can be found
      even from the results of a single condensed Monte Carlo simulation. The
      application of similarity rules may reduce further the number of Monte Carlo
      simulations that are needed to describe the influence of the distribution of
      scattering angles on the results.

PMID- 20802709
TI  - Optical properties of human dermis in vitro and in vivo.
AB  - Condensed Monte Carlo simulation results have been used for calculating
      absorption and reduced scattering coefficients from the literature data on the
      measured total transmittance and total reflectance of samples of the human skin
      in vitro. The results of several measuring methods have been compared. We have
      also estimated the range for absorption coefficients and reduced scattering
      coefficients at 660 and 940 nm from measured intensities at the skin surface as a
      function of the distance from the location where the light enters the skin by
      using condensed Monte Carlo simulations for a homogeneous semi-infinite medium.
      The in vivo values for the absorption coefficients and the reduced scattering
      coefficients appear to be much smaller than the values from the in vitro
      measurements, that have been assumed until now. The discrepancies have been
      discussed in detail. Our in vivo results are in agreement with other in vivo
      measurements that are available in the literature.

PMID- 20802710
TI  - Photon hitting density.
AB  - Optical and near-IR spectroscopy and imaging of highly scattering tissues require
      information about the distribution of photon-migration paths. We introduce the
      concept of the photon hitting density, which describes the expected local time
      spent by photons traveling between a source and a detector. For systems in which
      photon transport is diffusive we show that the hitting density can be calculated
      in terms of diffusion Green's functions. We report calculations of the hitting
      density in model systems.

PMID- 20802712
TI  - Heat-induced structural alterations in myocardium in relation to changing optical
      properties.
AB  - In canine myocardium, organelles fragmented progressively with temperatures, at
      45-75 degrees (1000-s exposure). This correlated with a gradual decrease in the
      anisotropy of scattering.

PMID- 20802711
TI  - Continuous pneumothorax monitoring by remittance measurement.
AB  - The feasibility of a noninvasive method, based on a remittance measurement, to
      monitor continuously for the occurrence of pneumothorax in neonates under
      ventilation, was investigated through animal experiments. Light from a He-Ne
      laser (632.8 nm) or a semiconductor laser (790 nm) was incident on the chest wall
      of rabbits and piglets. The remittance was measured as a function of distance
      from the source. Remittances under physiological conditions were compared with
      remittances during the introduction of an artificial pneumothorax and with
      remittances during inflation of the pleural space. The remittance varied with a
      frequency similar to the respiratory frequency. The amplitude of these variations
      changed as a function of the volume of air that was introduced into the pleural
      space (rabbits/He-Ne laser, p < 0.025; piglets/semiconductor laser, p < 0.01). We
      conclude that optical measurements are potentially usable for monitoring
      continuously for the occurrence of a pneumothorax in neoatology.

PMID- 20802713
TI  - Laser fluorescence spectroscopy from human spermatozoa.
AB  - The native fluorescence spectra, intensity dependence on sperm density,
      relaxation decay time, and polarization were investigated on spermatozoa and
      their components (sperm heads and sperm tails) under laser excitation.

PMID- 20802714
TI  - Two-fiber laser Doppler velocimetry in blood: Monte Carlo simulation in three
      dimensions.
AB  - Laser Doppler velocimetry in blood when fiber-optic catheters are used is limited
      by the effects of multiple scattering and flow disturbance produced by the
      catheter. To minimize the effects of flow disturbances, the system should be
      designed to project the velocity-sensing region as far as possible from the
      surface of the catheter. Because of multiple scattering, determining the region
      of sensitivity requires the use of transport theory. We present numerical results
      of Monte Carlo simulations of the spatial Doppler sensitivity field of a two
      fiber velocimeter. The simulations show that a peak of sensitivity can be
      projected approximately 0.5 mm from the fiber tips (at 685 nm); the use of longer
      wavelengths would increase this distance somewhat. The generation of such a peak
      requires overlapping the partially spatially coherent propagation regions of the
      two fibers, which in turn depends strongly on the relative orientation of the
      fibers, even though much of the scattered light is diffuse.

PMID- 20802715
TI  - Light dosimetry: effects of dehydration and thermal damage on the optical
      properties of the human aorta.
AB  - The influences of dehydration and thermal damage on in vitro optical properties
      of human aorta were studied. The absorption coefficient increased by 20-50%,
      especially in the visible range when at least 40% of total tissue weight was lost
      as a result of dehydration. The reduced scattering coefficient increased by 10
      45% in the visible and 30% to over 150% in the near IR after the tissue samples
      were heated in a constant temperature water bath at 100 degrees C for 300 +/- 10
      s. This study implies that dehydration and protein coagulation during
      photothermal treatment of tissue are important factors altering optical
      properties of tissue.

PMID- 20802716
TI  - Dynamic optical properties of collagen-based tissue during ArF excimer laser
      ablation.
AB  - Various attenuation mechanisms affecting the absorption of ArF excimer laser
      light in collagenous tissues have been studied. Temporal distortion of the laser
      pulse reflected from the cornea has been observed over a range of incident pulse
      fluences including the ablation threshold. Reflected pulse shortening begins near
      the ablation threshold and advances with increasing fluence. The measurement of
      laser light scattered 30 degrees off specular axis from collagen gel targets
      indicates that the reflected-pulse distortion is partially a result of
      scattering. Collagen film transmission studies show an increase in 193-nm light
      transmission in ablation conditions. These nonlinear attenuation mechanisms may
      impact significantly on the photoablation process.

PMID- 20802717
TI  - Tissue tearing caused by pulsed laser-induced ablation pressure.
AB  - Pressure induced by ablative pulses of laser radiation is shown to correlate with
      the mechanical disruption of tissue. The ablation pressure induced during Er:YSGG
      laser irradiation of skin, liver, and aorta was calculated from a ballistic
      pendulum-based measurement of recoil momentum. The ejected material and ablation
      crater were examined grossly and microscopically after ablation. A gas-dynamic
      model of laser-induced vaporization was used to understand the measured
      pressures. The results show that mechanical disruption of tissue occurs when the
      ablation pressure exceeds the strength of the irradiated tissue at sites of
      intrinsic weakness.

PMID- 20802718
TI  - Scaling relationships for theories of anisotropic random walks applied to tissue
      optics.
AB  - Monte Carlo simulations are used to discern scaling relationships for photon
      migration occurring within homogeneous, anisotropic scattering media of semi
      infinite extent. Special attention is given to events associated with short path
      lengths. Empirical scaling relationships for path lengths and surface intensities
      are shown to agree with a consistency equation derived in an earlier study of
      anisotropic random walks. They are augmented here by a procedure that accounts
      for concomitant scaling of optical absorption coefficients. Results then are used
      to transform expressions that were obtained previously by analytical random-walk
      theory developed for an isotropic scattering model of photon migration.
      Quantities that are studied include the diffuse surface reflectance, the depth
      distribution of the fluence, and the time-resolved intensity of backreflected
      photons.

PMID- 20802719
TI  - Temperature control during laser vessel welding.
AB  - A technique is described for the computer control of temperature during laser
      vessel welding. The technique is based on the use of thermal feedback from a
      calibrated IR sensor. The utilization of thermalfeedback makes it possible for
      welding to be performed at a quasiconstant temperature. An experimentalsystem
      based on this concept has been developed and evaluated in mock anastomoses with
      vasculartissue. A computer simulation of laser vessel welding with a one
      dimensional heat conduction model hasbeen performed. Model parameters have been
      adjusted so that the relative effect of laser penetrationdepth and tissue
      dehydration as well as the role of thermal feedback in limiting the peak
      surfacetemperature can be studied. The results of the mock anastomoses are
      discussed in light of the computer model.

PMID- 20802720
TI  - Excimer, Ho:YAG, and Q-switched Ho:YAG ablation of aorta: a comparison of
      temperatures and tissue damage in vitro.
AB  - The adjacent thermal and mechanical tissue damage after normal-mode Ho:YAG (pulse
      length = 250 mus, lambda = 2.09 mum), Q-switched Ho:YAG (pulse length = 200 ns,
      lambda= 2.09 mum), and excimer (pulse length = 120 ns, lambda = 308 nm) pulsed
      laser irradiation of human thoracic aorta samples was studied in vitro. Surface
      temperatures were monitored during laser irradiation with an IR camera in air or
      a thermocouple in saline. Histological analysis of the irradiated sites was
      performed to assess thermal and mechanical damage to tissue surrounding the
      crater. The ablation of aortic tissue with any of the lasers resulted in a
      temperature buildup inside the tissue; this effect was most significant for the
      IR wavelength. Mechanical damage was observed in all cases but was most
      pronounced for the Q-switched Ho:YAG laser. Excimer ablation in air left behind a
      smooth surface; however, under saline the result was a much rougher surface.

PMID- 20802721
TI  - Double-stage picosecond Kerr gate for ballistic time-gated optical imaging in
      turbid media.
AB  - We demonstrate that use of a picosecond double-stage Kerr gate system results in
      a 3-orders-of magnitude improvement in signal-to-noise ratio and a threefold
      improvement in shutter speed comparedwith those of a single-stage Kerr gate.

PMID- 20802722
TI  - Quantification of the hematoporphyrin derivative by fluorescence measurementusing
      dual-wavelength excitation anddual-wavelength detection.
AB  - A theory is presented describing a method for quantitative measurement of
      fluorophores in vivo. The method employs a combination of two-wavelength
      excitation and two-wavelength detection. A dimensionless fluorescence ratio is
      defined. The theory predicts that this ratio is a function of the concentration
      of the fluorophore only and is independent of optical properties, independent of
      geometrical parameters, and independent of autofluorescence. Experiments using a
      O.1-10-microg/mL hematoporphyrin derivative in a tissue phantom with the optical
      properties of the dermis show good agreement with theory.

PMID- 20802723
TI  - Spectral optical-density measurements of small particles and breast tissues.
AB  - The optical density of breast tissues without blood is found to be relatively
      constant from 320 to 800 nm, indicating a relatively independent scattering cross
      section over this wavelength region.

PMID- 20802724
TI  - Ultrafast laser-pulse transmission and imaging through biological tissues.
AB  - The transmission of 100-fs ultrafast laser pulses through biological tissues was
      measured by using femtosecond and picosecond time-resolved detection techniques.
      The broadening of transmitted pulses was found to increase as the thickness of
      the biological tissue increases. The absence of a distinct ballistic pulse
      transmitted through a relatively thin tissue is in sharp contrast with the pulse
      transmission through a random medium of discrete scatterers. Because of the
      continuous variation of the dielectric constant in tissue, the photons undergo
      scattering through the tissue, travel in various small zigzag least optical
      paths, and form a broadened early-arriving portion of the transmitted pulse. Even
      in the absence of a well-defined ballistic pulse, we can image an opaque object
      hidden inside a tissue as thick as 6.5 mm with submillimeter resolution by
      selecting the early-arriving portion of the transmitted pulse.

PMID- 20802725
TI  - Determining the optical properties of turbid mediaby using the adding-doubling
      method.
AB  - A method is described for finding the optical properties (scattering, absorption,
      and scattering anisotropy) of a slab of turbid material by using total
      reflection, unscattered transmission, and total transmission measurements. This
      method is applicable to homogeneous turbid slabs with any optical
      thickness,albedo, or phase function. The slab may have a different index of
      refraction from its surroundings and may or may not be bounded by glass. The
      optical properties are obtained by iterating an adding-doubling solution of the
      radiative transport equation until the calculated values of the reflection and
      transmission match the measured ones. Exhaustive numerical tests show that the
      intrinsic error in the method is < 3% when four quadrature points are used.

PMID- 20802726
TI  - Effects of irradiance and spot size on pulsed olmium laser ablation of tissue.
AB  - Threshold radiant exposures for pulsed holmium laser ablation of tissue were
      measured with a high-speed framing camera. The effects of laser irradiance and
      beam size on ablation threshold were investigated. Threshold radiant exposure
      decreased with increasing laser irradiance over the range of 10(5)-10(7) W/cm(2).
      Over the range of spot sizes examined (243-970 microm) an increase in the laser
      beam diameter reduced the laser irradiance required for ablation. At larger spot
      sizes the ablation event was occasionally initiated from multiple sites. These
      results suggest that the rate of energy deposition and laser-beam geometry affect
      the events preceding the onset of ablation and should be considered when pulsed
      laser ablation of tissue is modeled or quantified.

PMID- 20802727
TI  - Medical transillumination imaging using short-pulse diode lasers.
AB  - The recently introduced time-resolved technique for enhanced medical
      transillumination imaging has been demonstrated for the important case of a diode
      laser transmitter. This type of gated-viewing technique utilizes early received
      light only to reject multiply scattered, delayed light, normally blurring the
      image. Human breast-cancer detection is demonstrated in vitro, and the
      observations are explained by using theoretical modeling and tissue phantom
      experiments.

PMID- 20802728
TI  - Coherent backscattering in biological media: measurement and estimation of
      optical properties.
AB  - We measured the coherent backscattering of light from milk solutions and
      biological tissues by using a He-Ne laser (633 nm) and a CCD array as a detector.
      A coherent peak from the milk solutions could bemeasured with a single exposure.
      However, ensemble averaging was required for coherent peaks to be produced from
      solid media such as tissue samples. By fitting experimental data to an existing
      model numerically, effective scattering and absorption coefficients were
      estimated. They were compared with those computed from integrating sphere
      measurements. Effective scattering coefficients computed by the two different
      methods were in good agreement for high-scattering media. However, higher
      absorption was estimated by the coherent peak method.

PMID- 20802729
TI  - Optical properties of human gallbladder tissue and bile.
AB  - Knowledge of the optical properties of biliary tract tissues is useful for aiding
      in the development and understanding of clinical applications of lasers in the
      biliary tract. Human gallbladder and bile specimens were obtained during
      laproscopic cholecystectomy. The diffuse remittance and transmission of the
      samples were determined from 350 to 2450 nm. Collimated transmission was
      determined at 633 and 2100 nm. Using one-dimensional diffusion theory, we
      calculated micro(s), micro(a), and g as a function of wavelength. Both
      gallbladder and bile show absorption peaks at 1.4 and 1.9 microm. Bile has a peak
      at 400 nm; gallbladder has peaks at 410 and 550 nm. The absorption peaks are
      correlated with known tissue chromophores. The effect of the sample preparation
      on the results is discussed.

PMID- 20802730
TI  - Ultraviolet confocal fluorescence microscopy of the in vitro cornea: redox
      metabolic imaging.
AB  - A laser scanning microscope was fitted with two argon-ion lasers that provided
      wavelengths in the regions of 364, 488, and 514 nm. A Zeiss water objective of 25
      x , with a numerical aperture of 0.8, corrected for the UV, was used to measure
      the fluorescence from optical sections of freshly enucleated rabbit eyes. The
      confocal microscope was used in both the reflected and fluorescent modes to image
      in situ epithelial and endothelial cells. An excitation wavelength of 364 nm and
      emission at 400-500 nm were used to image the fluorescence from reduced pyridine
      nucleotides. We demonstrate the feasibility of two-dimensional fluorescent
      confocal imaging of reduced pyridine nucleotides in corneal epithelial and
      endothelial cells.

PMID- 20802731
TI  - Experimental evaluation of mathematical models for predicting the thermal
      response of tissue to laser irradiation.
AB  - We investigated the ability of mathematical models to predict temperature rises
      in biological tissue duringlaser irradiation by comparing calculated values with
      experimental measurements. Samples of normal human aorta, beef myocardium, and
      polyacrylamide gel were irradiated in air with an argon laser beam, while surface
      temperatures were monitored with an IR camera. The effects of different surface
      boundary conditions in the model predictions were examined and compared with the
      experimental data. It was observed that, before a temperature of 60 degrees C was
      reached, the current mathematical models were capable of predicting tissue
      surface temperature rises with an accuracy of 90% for a purely absorbing medium
      and with an accuracy of 75% for biological tissue (a scattering medium). Above 60
      degrees C, however, the models greatly overestimated temperature rises in both
      cases. It was concluded that the discrepancieswere mainly a result of surface
      water vaporization, which was not considered in current models and which was by
      far the most significant surface-heat-loss mechanism for laser irradiation in
      air. The inclusion of surface water vaporization in the mathematical models
      provided a much better match between predicted temperatures and experimental
      results.

PMID- 20802732
TI  - Properties of photon density waves in multiple-scattering media.
AB  - Amplitude-modulated light launched into multiple-scattering media, e.g., tissue,
      results in the propagation of density waves of diffuse photons. Photon density
      wave characteristics in turn depend on modulation frequency (omega) and media
      optical properties. The damped spherical wave solutions to the homogeneous form
      of the diffusion equation suggest two distinct regimes of behavior: (1) a high
      frequency dispersion regime where density wave phase velocity V(p) has a
      radicalomega dependence and (2) a low-frequency domain where V(p), is frequency
      independent. Optical properties are determined for various tissue phantoms by
      fitting the recorded phase (?) and modulation (m) response to simple relations
      for theappropriate regime. Our results indicate that reliable estimates of tissue
      like optical properties can be obtained, particularly when multiple modulation
      frequencies are employed.

PMID- 20802733
TI  - Numerical method for studying the detectability of inclusions hidden in optically
      turbid tissue.
AB  - We introduce an efficient numerical method for studying the detectability of
      absorptive inclusions in a multiple-scattering optical medium. Use of the method
      is demonstrated by the forward calculation of integrated and time-gated photon
      intensities. Schemes for positioning the light source above an inclusion and
      otherwise determining the location of a hidden object, involving either reflected
      or transmitted reemissions, are discussed as examples. They are investigated for
      several illustrative models, and images are calculated as a function of the size
      and shape of the inclusion.

PMID- 20802734
TI  - Patents.
AB  - 4,983,004; 4,983,022; 4,984,872; 5,033,853; 5,048,910; 5,050,989; 5,071,210;
      5,073,006; 5,073,010; 5,078,464; 5,090,807.

PMID- 20802735
TI  - Optical fractal synthesizer: concept and experimental verification.
AB  - An application of optical parallel processing in the generation of fractal images
      is presented. Iterated function systems [M. Barnsley, Fractals Everywhere
      (Academic, Boston, Mass., 1988), Chap. 3] are the basis of the operation, which
      can be easily implemented with optical techniques. An optical fractal synthesizer
      is considered to compute iterated function systems effectively with the
      advantages of optical processing in data continuity as well as parallelism. As an
      instance of the optical fractal synthesizer, an experimental system consisting of
      two optical subsystems for affine transformation and a TV-feedback line is
      constructed. Several experimental results verify the principle and show the
      processing capability of the optical fractal synthesizer.

PMID- 20802736
TI  - Redundant binary number representation for an inherently parallel arithmetic on
      optical computers.
AB  - A simple redundant binary number representation suitable for digital-optical
      computers is presented. By means of this representation it is possible to build
      an arithmetic with carry-free parallel algebraic sums carried out in constant
      time and parallel multiplication in log N time. This redundant number
      representation naturally fits the 2's complement binary number system and permits
      the construction of inherently parallel arithmetic units that are used in various
      optical technologies. Some properties of this number representation and several
      examples of computation are presented.

PMID- 20802737
TI  - Optical realization of a Clos nonblocking broadcast switching network with
      constant time network control algorithm.
AB  - The Clos interconnection network is one of the earliest multistage
      interconnection networks. Recently, a necessary condition on the number of middle
      stage switches required to achieve broadcast capability was presented [Tech. Rep.
      JHU 90/04 (Computer Science Department, Johns Hopkins University, Baltimore, Md,
      1990)]. A linear time control algorithm that determines whether a new input
      request is feasible or not was also provided. Here, the special characteristics
      of optics are used to provide a constant time parallel realization of the network
      control setup. This permits a reconfigurable Clos broadcast network.

PMID- 20802738
TI  - Holographic grating formation in poly(spiropyran I-glutamate).
AB  - An argon-ion laser interferometer (0.3638 or 0.488 microm) wrote photoreversible
      holographic grating (fringe spacing 0.39-100 microm) on spin-cast thin films (5
      microm thick) of poly(spiropyran l-glutamate).

PMID- 20802739
TI  - Block-quantized binary-phase holograms for optical interconnection.
AB  - A block-quantized binary-phase hologram consisting of a binary-phase hologram and
      a phase mask is investigated for use in optical interconnection. A simulated
      annealing algorithm is used to determine the phase pattern of the binary hologram
      and the phase of the mask required to achieve high diffraction efficiency and
      suppression of unwanted spots. Block-quantized binary-phase holograms encoded
      with the simulated annealing algorithm are fabricated using electron-beam
      lithography and chemical etching. The results from the optical experiments that
      use these holograms agree well with those from the computer simulations.

PMID- 20802740
TI  - Effect and use of exposure control in vibration analysis using TV holography.
AB  - A time-averaged recording of a sinusoidally vibrating object reconstructs a
      fringe function, which is determined by the ratio between the exposure time and
      the vibration period. For short exposures, compared with the vibration period,
      the fringe function is highly dependent on the number of vibration cycles
      recorded and on the starting point of the exposure in the vibration cycle. When
      several fringe functions that are recorded at different parts of the vibration
      cycle are added, the resulting averaged fringe function is similar to the normal
      J(o)(2) function, even at short exposures. The frequency ranges at which
      numerical analysis can be used in these two cases are defined, and the result of
      short exposures permitting digital fringe analysis, even under extremely unstable
      situations, is demonstrated. Extending the standard video exposure time permits
      recording vibrations at low frequencies as the normal J(o)(2) function and
      improves the light economy.

PMID- 20802741
TI  - Optical-digital method of local histogram calculation by threshold decomposition.
AB  - A theorem for calculating the local histograms of a gray-scale input image by
      means of convolution of input-image binary slices with a binary kernel is
      presented and proved. The calculation of the local histograms of a gray-scale
      image for all resolution cells and its arbitrary neighborhoods is optically
      implemented in a shadow-casting correlator. The choice of different rank-order
      values from the local histograms can lead to a wide spectrum of nonlinear
      filtration algorithms.

PMID- 20802742
TI  - Extracting number and relative positions of multiple extended objects from
      autocorrelation data.
AB  - Information describing a scene must often be inferred from its spatial
      autocorrelation function (or its power spectrum). Such information can be used to
      establish constraints or trial solutions in iterative image reconstruction, or it
      can be used to fit scene object models directly to nonimage data. The most basic
      scene information consists of the number of objects present and their relative
      positions, which is prerequisite to describing the individual objects. Unfolding
      point-object positions from a noise-free autocorrelation has been addressed
      previously. Many applications involve extended objects, however, inviting the
      problematic overlap of autocorrelation features. Furthermore, data are rarely
      noise-free. A method of logically unfolding object positions from an
      autocorrelation is described, and the impact of noise, redundancy, and finite
      object size on the process is assessed.

PMID- 20802743
TI  - Error-diffusion binarization for joint transform correlators.
AB  - It is shown that the error-diffusion method is advantageous in the production of
      a binarized power spectrum interference pattern in joint transform image
      correlator (JTC) configurations, leading to better definition of the correlation
      location. A modified error-diffusion method for JTC configurations described here
      is effective also for cases involving noisy correlation planes. A computer
      simulation comparison of correlation-peak quality, also in the presence of
      additive white noise, was carried out by using several performance criteria. The
      classical continuous JTC was compared with a binarized JTC, whereby the
      binarization method for a normalized and nonlinearly scaled Fourier-transform
      interference intensity pattern was based on either error-diffusion or hard
      clipping techniques that used a constant threshold value. The suggested
      operations of normalization and nonlinear scaling are essentially equivalent to
      truncation and normalization. The error-diffusion binary JTC yields
      autocorrelation characteristics that are superior to those of the hard-clipping
      binary JTC over the whole nonlinear scaling range of the Fourier-transform
      interference intensity for all noise levels considered. The binary JTC, binarized
      in either the error-diffusion or the hard-clipping binarization method, is
      superior to the classical continuous JTC over a certain nonlinear scaling range
      and up to a specific level of additive-input white noise. In addition, the
      binarized cross-correlation JTC selectivity is generally better than that of the
      continuous JTC, especially when high levels of additive-input white noise are
      present. Preliminary experimental results, which can be obtained in real time by
      using a single spatial light-modulator, are presented.

PMID- 20802744
TI  - Real-time color image correlation with a color liquid-crystal television and a
      Fresnel holographic filter.
AB  - Incoherent color image correlation with a multiwavelength Fresnel holographic
      filter and a color liquid-crystal television as a real-time input device is
      demonstrated.

PMID- 20802745
TI  - Adaptive real-time architectures for phase-only correlation.
AB  - A video-rate correlator can be constructed with a phase-only spatial light
      modulator and a CCD camera. The phase of the Fourier transform of a signal and a
      reference image is determined by fringe-scanning interferometry. The two measured
      phase images are then subtracted. The optical Fourier transform of this
      difference produces the phase-only correlation response. This system can update
      both signal and reference images with live scenery. Currently, only the joint
      transform correlator has demonstrated this degree of adaptivity in real time.
      Physically compact versions of the correlator can be built with a single spatial
      light modulator and a Fourier-transform lens.

PMID- 20802746
TI  - Three-dimensional speckle measurements with a diffraction grating.
AB  - A method to measure three-dimensional displacements through a speckle technique
      is proposed. This measurement is possible by adding a diffraction grating to the
      classical bidimensional Burch experimental setup. The principle is described and
      results are discussed.

PMID- 20802747
TI  - Speckle-free image amplification by two-wave coupling in a photorefractive
      crystal.
AB  - A technique of speckle-noise reduction for an image amplified by two-wave
      coupling with a photorefractive crystal is proposed. The spatial coherence for
      the axis along the fringe formed in the photorefractive crystal is reduced to
      remove the speckle, but the spatial coherence for the axis vertical to the fringe
      is unaltered. This is obtained by rotating a mirror to deflect the illumination
      beams one dimensionally for both the signal and reference patterns during the
      exposure of the hologram. Because of the imageholography configuration, the
      images of the signal and the reference do not move on the photorefractive crystal
      as the two beams deflect. The beam deflection can be faster than the response of
      the photorefractive crystal. Some experimental results for the image
      amplification with the technique developed are presented, and they are compared
      with results obtained without speckle-noise reduction. Fringe deformation caused
      by deflection of the signal and reference beams is analyzed.

PMID- 20802748
TI  - Analysis technique for the measurement of a three-dimensional object shape.
AB  - A new analysis technique for the automatic measurement of a three-dimensional
      object shape is proposed and verified experimentally. In this structured-light
      technique the process of projecting a grating pattern upon the object is
      considered for using carrier frequencies to modulate the object spectrum in the
      spatial frequency domain or to add a reference surface to the data in the space
      domain. The projected fringes are considered as interferometric fringes;
      therefore the interferogram analysis technique can be introduced into the
      measurement of a three-dimensional object shape.

PMID- 20802749
TI  - Use of electron-trapping materials in optical signal processing. IV: Parallel
      incoherent image subtraction.
AB  - Novel electron trapping materials are inherently capable of performing
      subtraction over a wide dynamic range. The application of the electron trapping
      materials to parallel incoherent image subtraction is described in detail, and
      experimental results are presented.

PMID- 20802750
TI  - Beam-deflection optical tomography of the refractive-index distribution based on
      the Rytov approximation.
AB  - A method of beam-deflection optical tomography based on the Rytov approximation
      of the wave equation is proposed. A linear relation between the deflection angle
      and the refractive-index distribution from the Rytov approximation and an
      equation of geometrical optics is derived. The tomographic reconstruction in this
      method is reduced to the solution of a system of linear equations. Experimental
      results show that this method can reconstruct strongly refracting fields from
      projection data of six view angles.

PMID- 20802752
TI  - Nasa patter.

PMID- 20802751
TI  - Symbolic substitution system for data compression.
AB  - A new application of symbolic substitution is presented for string matching with
      the goal of data compression. A temporal sequence of input symbols is mapped onto
      a two-dimensional array that contains a tree structure, which in turn is mapped
      into another array for string generation. A symbolic substitution system and the
      necessary rules are developed to implement the mapping of the input mapping and
      the generation of an output sequence. A nonadaptive scheme of compression and
      decompression is described first, followed by an adaptive scheme with additional
      rules for the dynamic adaptation process.

PMID- 20802753
TI  - Introduction to the LACA III Feature Issue of Applied Optics.
AB  - This is the introduction to the Applied Optics feature issue on Laser
      Applications to Chemical Analysis III. The issue is an outgrowth of the Topical
      Meeting on Laser Applications to Chemical Analysis III that was held in January
      1992.

PMID- 20802754
TI  - Semiconductor laser-induced fluorescence detection in picoliter volume flow
      cells.
AB  - A visible semiconductor laser-induced fluorescence detection system for
      ultratrace chemical analysis of nanoliter-to-picoliter samples is optimized and
      characterized in detail. With low-power semiconductor lasers emitting at 675 and
      639 nm for excitation, the best limit of detection is 8000 molecules for a model
      fluorescent compound (1,1',3,3,3',3'-hexamethylindotricarbocyanine iodide) in an
      ethanol solution. Fused silica capillaries with inner diameters between 250 and
      11 microm were employed as picoliter volume flow cells, which permits the use of
      the system in miniaturized separation techniques such as packed and open tubular
      liquid chromatography and capillary electrophoresis.

PMID- 20802755
TI  - How to find the sensitivity limit for DNA sequencing based on laser-induced
      fluorescence.
AB  - The sensitivity limit for one-lane DNA sequencing based on laser-induced
      fluorescence is derived by statistical means. A closed-form expression for the
      sequencing error probability as a function of the signal strength and of the
      differences in the fluorescence properties of the labels is given. Fluctuations
      of the signal caused by photodestruction of the molecules cannot be neglected.
      The expected sequencing error probability is expressed in terms of the number of
      molecules and the physical parameters of the measurement. This equation can be
      used in many ways to design and optimize sequencing experiments.

PMID- 20802756
TI  - Tunable diode laser ratio measurements of atmospheric constituents by employing
      dual fitting analysis and jump scanning.
AB  - We present two new approaches in tunable diode laser absorption spectroscopy
      (TDLAS) for measuring the ratio of two components with high precision. These
      techniques, dual line fitting analysis and jump scanning, greatly extend the
      versatility and applicability of TDLAS. Three important applications for these
      approaches are discussed. In addition, we demonstrate the capability to quantify
      features that are different in amplitude by a factor of 22.4 with a precision of
      0.3%. Such a precision is also achieved for features that are different in
      amplitude by a factor of 12.9 and separated by 0.2363 cm(-1). Both jump scanning
      and dual line fitting analysis are being used on a routine basis in a laboratory
      kinetics study to measure simultaneously the concentrations of H(2)O and NO,
      whose features are separated by 0.4866 cm(-1).

PMID- 20802757
TI  - Ultrasensitive spectral trace detection of individual molecular components in an
      atmospheric binary mixture.
AB  - We present what is, to our knowledge, the first demonstration of the application
      of the laser homodyne interferometric technique to the quantitative
      identification of individual trace molecular constituents of a binary mixture in
      an ambient atmospheric background. Operation of the laser interferometric
      detection system to within a factor of 26 of the theoretical quantum noise limit,
      without extensive vibrationisolation, is observed. We realize the spectral
      identification of SF(6) and CF(2)Cl(2) mixed in various trace concentrations,
      without significant cross interference, using molecular spectral features
      overlapping the 10P CO(2) laser transitions.

PMID- 20802758
TI  - Applications of a tunable CO(2) sideband laser for high-resolution spectroscopic
      measurements of atmospheric gases.
AB  - A microwave-tuned CO(2) sideband laser system for high-resolution spectroscopic
      measurements is described. The system is capable of measuring, accurately and
      reliably, absorption line frequencies, line strengths, self-broadened Lorentz
      linewidths and line frequency shifts that are due to pressure in the midinfrared.
      Several transitions of NH(3) are measured and the results are compared with the
      1991 edition of the high-resolution transmission molecular absorption (HITRAN)
      database.

PMID- 20802759
TI  - Single-photon laser ionization time-of-flight mass spectroscopy detection in
      molecular-beam epitaxy: application to As(4), As(2), and Ga.
AB  - Single-photon laser ionization time-of-flight mass spectroscopy (TOF-MS) is used
      to monitor fluxes of As(4), As(2), and Ga, species that are important in
      molecular-beam epitaxy of GaAs. With this technique, fluxes of multiple chemical
      species above a substrate can be measured noninvasively and in real time during
      conventional molecular-beam epitaxy. Additionally, the geometry of the single
      photon ionization TOF-MS permits simultaneous film-growth monitoring by using
      techniques such as reflection highenergyelectron diffraction (RHEED). Here gas
      phase arsenic and gallium beams are ionized by a single 118-nm (10.5-eV) photon
      and detected with a TOF-MS. The 118-nm photons are produced by frequency tripling
      355-nm light from a pulsed Nd:YAG laser in Xe. With single-photon ionization,
      less than 0.4% ofthe As(4)(+) signal fragments to As(2)(+). Neither As(4)(+) nor
      As(2)(+) fragments to As(+) at 118 nm. The relative ionization probability of
      As(4)/As(2) at 118 nm is approximately 4:1. This technique promises to be a
      powerful tool for analyzing most III-V and II-VI molecular-beam epitaxy growth
      species.

PMID- 20802760
TI  - Tunable 17-microm laser spectrometer for optical absorption measurements of
      CH(4), C(2)H(4), and high-temperature HCl.
AB  - A tunable 1.7-microm cw F(2)(+)-center laser spectrometer system that is
      continuously tunable from 1.43 to 1.78 microm in wavelength and has aspectral
      linewidth (FVWM) of 0.07 cm(-1) is developed. This system is used to measure the
      2-0 rotational-vibrational absorption line profiles of hydrogen chloride (HCl) at
      high temperatures, the Boltzmann thermal equilibrium temperature, and to
      determine the extent of potential interference or overlap of the HCl lines with
      those that are due to hot water vapor. As a demonstration of the utility of the
      laser spectrometer system, it is also used to measure the spectra of methane
      (CH(4)) and ethylene (C(2)H(4)) near 1.65 microm, and is routed through a fiber
      optic cable to a remote site to detect a CH(4) plume.

PMID- 20802761
TI  - Molecular analysis by ionization of laser-desorbed neutral species.
AB  - A powerful molecular surface analysis technique for the analysis of complex
      materials, such as polymer/additive systems, consists of laser desorption of
      surface molecules and subsequent ionization of these gas-phase molecules with
      resonant or nonresonant laser ionization. These molecular ions are subsequently
      detected by Fourier-transform mass spectrometry or time-of-flight mass
      spectrometry. We show that different wavelengths for the postionization step
      permit selectivity that provides important additional information on the chemical
      makeup of these complex materials. Near-UV wavelengthsselectively ionize aromatic
      polymer additives, far-UV wavelengths photoionize other nonaromatic species; and
      vacuum-UV wavelengths provide access to all the desorbed species. In addition to
      these applied results, we study many fundamental issues of laser desorption, such
      as desorption thresholds, velocity distributions, postionization wavelength
      selectivity, etc. The Fourier-transform mass spectrometer and time-of-flight mass
      spectrometer are discussed in detail.

PMID- 20802762
TI  - Detection of trace amounts of Cr by two laser-based spectroscopic techniques:
      laser-enhanced ionization in flames and laser-induced fluorescence in graphite
      furnace.
AB  - The detectability of Cr in water solutions by two-step laser-enhanced ionization
      (LEI) in flames and two-step excitation laser-induced fluorescence in graphite
      furnace (LIF-GF) with nonresonant detection is investigated for what is, to our
      knowledge, the first time. A thorough investigation of possible excitation and
      detection routes for Cr for both techniques is given. The detection limit of Cr
      in water by the LEI technique was found to be 2 ng/mL, while the LIF-GF technique
      showed a detection limit of 1.4 pg (which corresponds to 0.3 ng/mL, with a 5
      microL sample volume), both of which are limited by contamination (from the
      burner head-nebulizer unit in the flame and from the graphite material in the
      furnace). A more sensitive two-step LEI excitation scheme than that used here is
      also proposed. A new technique for reducing fluctuations from blackbody radiation
      by using sequential detection of the blackbody radiation from one photomultiplier
      by two boxcar integrators is presented. A possible means of increasing the
      nonresonant signal in two-step excitation LIF-GF by adding small amounts of
      quenching enhancing N(2) to the Ar atmosphere gives no positive results. The
      influence of large amounts of Na on the detectability of Cr by LEI is
      investigated.

PMID- 20802763
TI  - Combined wavelength and frequency modulation spectroscopy: a novel diagnostic
      tool for materials processing.
AB  - By applying both low-frequency wavelength modulation and high-frequency phase
      modulation to a laser diode, we develop a sensitive, high-bandwidth chemical
      diagnostic tool that is applicable to a variety of gas-phase processing
      environments. Specific chemical species are identified and monitored through
      their infrared absorption spectra, and the modulation methods allow for sensitive
      detection that is free of window and other reflection-driven interference
      fringes. Absorbance limits of 5.3 x 10(-8) and 1.9 x 10(-7) are obtained for an
      AlGaAs diode laser and a lead-salt diode laser, respectively. We discuss
      applications to plasma etching and chemical vapor deposition.

PMID- 20802764
TI  - Study of high-temperature multiplex HCl coherent anti-Stokes Raman spectroscopy
      spectra.
AB  - A feasibility study of temperature measurement with multiplex HCl coherent anti
      Stokes Raman spectroscopy (CARS) is investigated. The HCl CARS spectra of a 100%
      HCl gas sample are recorded in a quartz sample cell placed in a furnace at 1 atm
      pressure and at different temperatures. The nonlinear susceptibility of HCl
      (chi(nr)(HCl)), which is measured with the present CARS experimental setup, is
      reported. The experimental spectra are fit by using a library of simulated HCl
      CARS spectra with a least-squares-fitting program to infer the temperature. The
      inferred temperatures from HCl CARS spectra are in agreement with thermocouple
      temperatures.

PMID- 20802765
TI  - Laser-based spectroscopic technique for fast and reliable measurements of
      lifetimes of atomic metastable states in combustive situations.
AB  - A technique for a fast and reliable determination of the lifetime of atomic
      metastable states in combustive situations, based on the laser-enhanced
      ionization technique, is developed. The typical time required for a determination
      of the lifetime of an atomic metastable state in a given local position in a
      combustive situation ranges from some seconds to a minute (depending on the
      signal-to-noise ratio). The lifetime of the lowest metastable state in Au in an
      acetylene-air flame, which is used as the pilot metastable state in this paper,
      was found to vary over one order of magnitude (between 600 ns and 8.8 micros),
      depending on the local stoichiometric conditions in the probe volume (which, in
      turn, is a function of the probing position and the fuel-air ratio fed to the
      flame). It is demonstrated that the probing of the lifetime of atomic metastable
      states by this new technique can thus be used as a sensitive tool for mapping
      local stoichiometric conditions in a flame.

PMID- 20802766
TI  - Spatially resolved multispecies and temperature analysis in hydrogen flames.
AB  - We report on spatially resolved simultaneous measurements of temperature and
      majority species concentrations along a line segment in a premixed laminar H(2)
      air flame. The results are obtained from Raman and Rayleigh scattering by using a
      narrow-band KrF excimer laser and a spectrally and spatially resolving detector
      system that consists of a high-throughput spectrometer and a gated, intensified,
      two-dimensional CCD camera. The data presented here are integrated over 100 laser
      shots. Absolute density profiles of N(2), O(2), H(2)O, and H(2), as well as
      temperature profiles at various heights through the flame, are presented. A
      discussion of the required calibration procedures and a summary of the necessary
      spectroscopic background are also included in this paper.

PMID- 20802767
TI  - Detection of OH in flames by using polarization spectroscopy.
AB  - The potentials of polarization spectroscopy in combustion studies are reported.
      This well-established technique of nonlinear laser spectroscopy is applied to the
      detection of OH molecules in a premixed acetylene-oxygen and a propane-air flame.
      The polarization spectrum is recorded in the A (2)Sigma-X(2)Pi(0, 0) band. The
      spatial distribution of OH is measured in the flames. The saturation of the
      signal as a function of the laser pulse intensity is also investigated.

PMID- 20802768
TI  - Analysis of metabolites in aqueous solutions by using laser Raman spectroscopy.
AB  - Laser Raman scattering is conducted on aqueous solutions that contain organic
      chemicals that include glucose, lactate, ascorbate, pyruvate, and urea. At the
      concentrations of interest (below 1.0 wt. %), these various metabolites are found
      to scatter light independently of each other, and the scattering is linearly
      proportional to their concentrations. Through proper subtraction of water
      background scattering, the spectrum that is due to metabolite scattering is
      obtained and the composition of the solution can be determined by fitting its
      Raman spectrum with a linear sum of the known pure metabolite spectra. The
      spectrum of rabbit aqueous humor is presented and the potential application of
      this analytical method, such as noninvasive glucose monitoring, is discussed.

PMID- 20802769
TI  - Intense backward Raman lasers in CH(4) and H(2).
AB  - The conversion efficiency of the first Stokes radiation generated by backward
      stimulated Raman scattering is measured in CH(4) and H(2) that are pumped by a
      third harmonic of a Nd:YAG laser in the 12-55-mJ energy range and in the 0.86
      6.00-MPa pressure range. Our experimental results show that CH(4) is a better
      Raman medium than H(2) at moderate pressures (a few megapascals) to efficiently
      generate backward Raman lines.

PMID- 20802770
TI  - Application of Raman spectroscopy to metal-sulfide surface analysis.
AB  - The surface products of electrochemically oxidized pyrite (FeS(2)) are
      investigated as a function of applied potential by using Raman spectroscopy. The
      parameters necessary for sulfur formation on the pyrite surface were determined.
      An optical multichannel apparatus, consisting of an argon laser, a triple
      spectrograph, and a charge-coupled-device detector, was utilized for the Raman
      measurements. The advantages of this system for surface characterization include
      high resolution and high sensitivity as well as the capability of identifying
      compounds and making in-situ measurements.

PMID- 20802771
TI  - Time-resolved emission studies of ArF-laser-produced microplasmas.
AB  - ArF-laser-produced microplasmas in CO, CO(2), methanol, and chloroform are
      studied by time-resolved emission measurements of the plasma decay. Electron
      densities are deduced from Stark broadening of the line profiles of atomic H, C,
      O, and Cl. Plasma ionization and excitation temperatures are determined from
      measurements of relative populations of ionic and neutral species produced in the
      plasmas. A discussion of the thermodynamic equilibrium status of ArF-laser
      microplasmas is presented. In general, the ArF-laser-produced microplasma
      environment is found to be similar in all the gases studied, in terms of both
      temperature (15,000-20,000 K) and electron density (10(17) cm(-3)-10(18) cm(-3)),
      despite the considerable differences observed in the breakdown thresholds and
      relative energies deposited in the various gases.

PMID- 20802772
TI  - Semiconductor laser-based measurements of quench rates in an atmospheric pressure
      plasma by using saturated-fluorescence spectroscopy.
AB  - Plasma diagnostics based on saturated fluorescence and absorption spectroscopy
      with a semiconductor (diode) laser are developed to probe the 4s(3)P(1) ?
      4p(3)D(2) transition (8425 A) of argon in an atmospheric pressure plasma produced
      by an inductively coupled plasma torch. Spatially resolved measurements of
      saturation intensity, nonradiative collisional transfer (quench) rate, and
      fluorescence yield (Stern-Volmer factor) are inferred from variations of spectral
      profile characteristics (line shape, line-center value, and frequency-integrated
      signal) with laser intensity. The results obtained by using fluorescence and
      absorption spectroscopy are mutually consistent in the analytical region 10 mm
      above the induction coil. The measured quench rates compare favorably with
      computed rates from a multilevel collisional radiative model that assumes a
      suprathermal electron population relative to the local thermodynamic equilibrium
      value at the kinetic temperature.

PMID- 20802773
TI  - Laser-based refractive-index detection for capillary electrophoresis: ray-tracing
      interference theory.
AB  - The fringe pattern observed in a far field after a laser beam illuminates a fused
      silica capillary immersed in a refractive-index matching material and filled with
      an analyte fluid is exploited to develop a sensitive optical detector for
      capillary chemical analysis. The inner capillary interface splits the laser beam
      into a reflected beam fan and a refracted beam fan, which, on overlapping in the
      far field, lead to interferences. The intensity and the position of the fringes
      for capillaries with 250 microm >/= i.d. (inner diameter) >/= 25 microm are well
      reproduced by the presented model. The calculation predicts the fringe pattern
      for various beam/i.d. geometric configurations and is used to optimize the
      performance of the nanoliter-picoliter refractive-index on-column detection
      studied. It is found that the best contrast corresponds to a capillary that is
      illuminated with a beam waist of omega(0) ~ i.d./12, which is off-center focused
      with an offset of s ~ i.d./2. For a given interference pattern, the fringes that
      are found to be more sensitive to Deltan are those that appear near the optical
      axis but still retain high intensity and contrast. The sensitivity increases
      approximately linearly with the fringe number, and the maximal fringe number
      increases proportionally with the i.d.

PMID- 20802774
TI  - Measurements of the refractive index of PbEuTe in the 3-10-microm region of the
      infrared.
AB  - The refractive index is measured for PbEuTe alloys in the 3.3-12-microm spectral
      region. Each alloy is grown with a different Eu concentration. The range of Eu
      concentrations studied is between 0.76 and 6.5 at. %. All measurements are
      performed on samples maintained at room temperature. We use a classical
      dispersion relation to establish a simple empirical relationship that describes
      the dependence of the refractive index as a function of both the percentage of
      the Eu concentration and the infrared wave number.

PMID- 20802775
TI  - High-efficiency and compact blue source: intracavity frequency tripling by using
      LBO and BBO without the influence of birefringence.
AB  - A new intracavity frequency-tripled laser resonator design that circumvents the
      birefringence interference problems normally associated with a laser resonator
      with two intracavity nonlinear crystals is developed. Two hundred mW of UV laser
      output in a TEM(00) mode is obtained from an intracavity frequency-tripled Nd:YAG
      laser; the 250-Hz pulsed input does not exceed 400 W. LBO and BBO nonlinear
      crystals are utilized for second-harmonic generation and third-harmonic
      generation, respectively. The peak power of the UV output measures 90 kW.

PMID- 20802776
TI  - Detector nonlinearity in frequency-domain fluorometry.
AB  - Frequency-domain fluorometry relies on the measurement of the phase and
      amplitudes of the Fourier components of the time-dependent fluorescence signal.
      Experimental results that show that a conventional photomultiplier is subject to
      intensity-dependent phase shifts are presented. The measurements indicate that
      this is a problem well below the maximum linear current of the photomultiplier
      response. These results have important implications in frequency-domain
      fluorescence anisotropy experiments, in which the parallel and the perpendicular
      components of the emission intensity are inherently different from one another: a
      phase shift can be introduced by the photomultiplier.

PMID- 20802777
TI  - Radiation and collisional energy transfer among the A (2)Pi(i) and X(2)Sigma(+)
      states of CN.
AB  - Laser-photolysis-laser-induced-fluorescence methods are used to characterize the
      collisional energy transfer between CN (A (2)Pi(i)) and (X (2)Sigma(+)) states
      and to measure radiative lifetimes of the (A (2)Pi(i)) nu' = 2-7 vibrational
      levels. In addition, use of the A (2)Pi(i) ? X (2)Sigma(+) system for the laser
      induced-fluorescence determination of (X (2)Sigma(+)) populations is demonstrated
      and discussed.

PMID- 20802778
TI  - Two-step selective photoionization of rubidium by using a Ti:sapphire laser.
AB  - A pulsed Ti:sapphire laser (TSL) is applied for what is, to our knowledge, the
      first time to laser isotope separation. A collimated beam of a rubidium atom with
      a natural isotope composition ((85)Rb, 72%; (87)Rb, 28%) is excited selectively
      from the ground state to the 5(2)P(3/2) state by irradiation of the single
      longitudinalmode TSL, and is photoionized by successive UV radiation. Ion spectra
      of each isotope indicate that each isotope is selectively photoionized.

PMID- 20802779
TI  - Water-vapor absorption line measurements in the 940-nm band by using a Raman
      shifted dye laser.
AB  - We report water-vapor absorption line measurements that are made by using the
      first Stokes radiation (930-982 nm) with HWHM 0.015 cm(-1) generated by a narrow
      linewidth, tunable dye laser. Forty-five absorption line strengths are measured
      with an uncertainty of 6% and among them are fourteen strong lines that are
      compared with previous measurements for the assessment of spectral purity of the
      light source. Thirty air-broadened linewidths are measured with 8% uncertainty at
      ambient atmospheric pressure with an average of 0.101 cm(-1). The lines are
      selected for the purpose of temperature-sensitive or temperature-insensitive
      lidar measurements. Results for these line strengths and linewidths are corrected
      for broadband radiation and finite laser linewidth (0.015 cm(-1) HWHM) broadening
      effects and compared with the high-resolution transmission molecular absorption.

PMID- 20802780
TI  - Gaussian-Schell model sources in one-dimensional first-order systems with loss or
      gain.
AB  - A detailed examination of the propagation of Gaussian-Schell model sources in one
      dimensional, possibly nonlossless, first-order systems is constructed. The laws
      of focusing are derived. The conditions for periodicity of the Gaussian-Schell
      model source are derived. This result generalizes the well-known result -2 </= A
      + D </= 2 for confinement of a perfectly coherent Gaussian beam to the partially
      coherent nonlossless case. When loss or gain is present several conditions must
      be satisfied simultaneously for periodicity. The self-consistent solutions are
      derived and the perturbation stability of the solutions is studied. A physical
      realization of an arbitrary nonlossless one-dimensional ABCD system is derived,
      which yields a convenient formula for deciding whether the ABCD system has loss
      or gain. Special attention is devoted to real and ripple systems.

PMID- 20802782
TI  - Synthesis of the N-(tert-butyloxycarbonyl)-O-triisopropylsilyl-D-pyrrolosamine
      Glycal of Lomaiviticin A & B via Epimerization of L-Threonine.
AB  - An efficient synthesis of the N-(tert-butyloxycarbonyl)-O-triisopropylsilyl-D
      pyrrolosamine glycal of lomaiviticin A (1) and lomaiviticin B (2) is described.
      The synthesis is highlighted by the epimerization of the L-threonine-derived
      oxazolidine 10 to oxazolidine 11. This key epimerization reaction, which serves
      to establish the correct relative configuration of the carbohydrate unit, was
      made possible only after conformational analysis indicated that substituted
      oxazolidines may adopt conformations that preclude enolization.

PMID- 20802781
TI  - Antibodies and the Brain: Lessons from Lupus.

PMID- 20802783
TI  - Micro-scale Modeling of Flow and Oxygen Transfer in Hollow Fiber Membrane Bundle.
AB  - The aim of this work was to develop a modeling approach to solve the flow and
      oxygen transfer when the blood passes through the hollow-fiber membrane bundle.
      For this purpose, a "two-region" modeling approach was developed regarding the
      hollow fiber and blood regions. The oxygen transfer in these regions was defined
      with separate diffusion processes. Two dimensional single and multi-fiber
      geometries were created and flow solutions were obtained for a non-Newtonian
      fluid. The convection-diffusion-reaction equation was solved to produce the
      oxygen partial pressure distributions. As a benefit of coupling the interstitial
      flow field into the oxygen transfer through the hollow-fiber membrane bundle, the
      membrane resistance was taken into consideration. Thus, varying oxygen partial
      pressures were observed on the outer fiber surface, which is contrary to the
      common simplifying assumptions of negligible membrane resistance and uniform
      oxygen content on the fiber surface (Traditional approach). It was illustrated
      that, the current approach can be utilized to predict the mass transfer
      efficiencies without overestimating as compared to the predictions obtained with
      the traditional approach. Utilization of the current approach was found to be
      beneficial for the geometries with lower packing density which allows significant
      P(O2) variations on the fiber surfaces. For the geometries with dense packings,
      the above simplifying assumptions could be applicable. The model predictions were
      validated with the experimental measurements taken from a benchmark device.

PMID- 20802785
TI  - Plasma-Assisted Synthesis of Carbon Nanotubes.
AB  - The application of plasma-enhanced chemical vapour deposition (PECVD) in the
      production and modification of carbon nanotubes (CNTs) will be reviewed. The
      challenges of PECVD methods to grow CNTs include low temperature synthesis, ion
      bombardment effects and directional growth of CNT within the plasma sheath. New
      strategies have been developed for low temperature synthesis of single-walled
      CNTs based the understanding of plasma chemistry and modelling. The modification
      of CNT surface properties and synthesis of CNT hybrid materials are possible with
      the utilization of plasma.

PMID- 20802784
TI  - Calciomics: prediction and analysis of EF-hand calcium binding proteins by
      protein engineering.
AB  - Ca(2+) plays a pivotal role in the physiology and biochemistry of prokaryotic and
      mammalian organisms. Viruses also utilize the universal Ca(2+) signal to create a
      specific cellular environment to achieve coexistence with the host, and to
      propagate. In this paper we first describe our development of a grafting approach
      to understand site-specific Ca(2+) binding properties of EF-hand proteins with a
      helix-loop-helix Ca(2+) binding motif, then summarize our prediction and
      identification of EF-hand Ca(2+) binding sites on a genome-wide scale in bacteria
      and virus, and next report the application of the grafting approach to probe the
      metal binding capability of predicted EF-hand motifs within the streptococcal
      hemoprotein receptor (Shr) of Streptococcus pyrogenes and the nonstructural
      protein 1 (nsP1) of Sindbis virus. When methods such as the grafting approach are
      developed in conjunction with prediction algorithms we are better able to probe
      continuous Ca(2+)-binding sites that have been previously underrepresented due to
      the limitation of conventional methodology.

PMID- 20802786
TI  - Investigation into Photoconductivity in Single CNF/TiO(2)-Dye Core-Shell Nanowire
      Devices.
AB  - A vertically aligned carbon nanofiber array coated with anatase TiO(2)
      (CNF/TiO(2)) is an attractive possible replacement for the sintered TiO(2)
      nanoparticle network in the original dye-sensitized solar cell (DSSC) design due
      to the potential for improved charge transport and reduced charge recombination.
      Although the reported efficiency of 1.1% in these modified DSSC's is encouraging,
      the limiting factors must be identified before a higher efficiency can be
      obtained. This work employs a single nanowire approach to investigate the charge
      transport in individual CNF/TiO(2) core-shell nanowires with adsorbed N719 dye
      molecules in dark and under illumination. The results shed light on the role of
      charge traps and dye adsorption on the (photo) conductivity of nanocrystalline
      TiO(2) CNF's as related to dye-sensitized solar cell performance.

PMID- 20802787
TI  - Synthesis of ZnGa(2)O(4) Hierarchical Nanostructure by Au Catalysts Induced
      Thermal Evaporation.
AB  - In this paper, ZnGa(2)O(4) hierarchical nanostructures with comb-like morphology
      are fabricated by a simple two-step chemical vapor deposition (CVD) method:
      first, the Ga(2)O(3) nanowires were synthesized and employed as templates for the
      growth of ZnGa(2)O(4) nanocombs; then, the as-prepared Ga(2)O(3) nanowires were
      reacted with ZnO vapor to form ZnGa(2)O(4) nanocombs. Before the reaction, the Au
      nanoparticles were deposited on the surfaces of Ga(2)O(3) nanowires and used as
      catalysts to control the teeth growth of ZnGa(2)O(4) nanocombs. The as-prepared
      ZnGa(2)O(4) nanocombs were highly crystallized with cubic spinel structure. From
      the photoluminescence (PL) spectrum, a broad band emission in the visible light
      region was observed of as-prepared ZnGa(2)O(4) nanocombs, which make it promising
      application as an optical material.

PMID- 20802788
TI  - Refuge sharing network predicts ectoparasite load in a lizard.
AB  - Living in social groups facilitates cross-infection by parasites. However,
      empirical studies on indirect transmission within wildlife populations are
      scarce. We investigated whether asynchronous overnight refuge sharing among
      neighboring sleepy lizards, Tiliqua rugosa, facilitates indirect transmission of
      its ectoparasitic tick, Amblyomma limbatum. We fitted 18 neighboring lizards with
      GPS recorders, observed their overnight refuge use each night over 3 months, and
      counted their ticks every fortnight. We constructed a transmission network to
      estimate the cross-infection risk based on asynchronous refuge sharing
      frequencies among all lizards and the life history traits of the tick. Although
      self-infection was possible, the network provided a powerful predictor of
      measured tick loads. Highly connected lizards that frequently used their
      neighbors' refuges were characterized by higher tick loads. Thus, indirect
      contact had a major influence on transmission pathways and parasite loads.
      Furthermore, lizards that used many different refuges had lower cross- and self
      infection risks and lower tick loads than individuals that used relatively fewer
      refuges. Increasing the number of refuges used by a lizard may be an important
      defense mechanism against ectoparasite transmission in this species. Our study
      provides important empirical data to further understand how indirectly
      transmitted parasites move through host populations and influence individual
      parasite loads.

PMID- 20802789
TI  - Novel Crystalline SiO(2) Nanoparticles via Annelids Bioprocessing of Agro
      Industrial Wastes.
AB  - The synthesis of nanoparticles silica oxide from rice husk, sugar cane bagasse
      and coffee husk, by employing vermicompost with annelids (Eisenia foetida) is
      reported. The product (humus) is calcinated and extracted to recover the
      crystalline nanoparticles. X-ray diffraction (XRD), transmission electron
      microscopy (TEM), high-resolution transmission electron microscopy (HRTEM) and
      dynamic light scattering (DLS) show that the biotransformation allows creating
      specific crystalline phases, since equivalent particles synthesized without
      biotransformation are bigger and with different crystalline structure.

PMID- 20802790
TI  - Nest desertion is not predicted by cuckoldry in the Eurasian penduline tit.
AB  - Engagement in extra-pair copulations is an example of the abundant conflicting
      interests between males and females over reproduction. Potential benefits for
      females and the risk of cuckoldry for males are expected to have important
      implications on the evolution of parental care. However, whether parents adjust
      parental care in response to parentage remains unclear. In Eurasian penduline
      tits Remiz pendulinus, which are small polygamous songbirds, parental care is
      carried out either by the male or by the female. In addition, one third of
      clutches is deserted by both male and female. Desertion takes place during the
      egg-laying phase. Using genotypes of nine microsatellite loci of 443 offspring
      and 211 adults, we test whether extra-pair paternity predicts parental care. We
      expect males to be more likely to desert cuckolded broods, whereas we expect
      females, if they obtain benefits from having multiple sires, to be more likely to
      care for broods with multiple paternity. Our results suggest that parental care
      is not adjusted to parentage on an ecological timescale. Furthermore, we found
      that male attractiveness does not predict cuckoldry, and we found no evidence for
      indirect benefits for females (i.e., increased growth rates or heterozygosity of
      extra-pair offspring). We argue that male Eurasian penduline tits may not be able
      to assess the risk of cuckoldry; thus, a direct association with parental care is
      unlikely to evolve. However, timing of desertion (i.e., when to desert during the
      egg-laying phase) may be influenced by the risk of cuckoldry. Future work
      applying extensive gene sequencing and quantitative genetics is likely to further
      our understanding of how selection may influence the association between
      parentage and parental care.

PMID- 20802791
TI  - A Copper-Carbodiimide Approach to the Phomopsin Tripeptide Side Chain.

PMID- 20802792
TI  - Spatial distribution and reproductive phenology of sexual and asexual Mastocarpus
      papillatus (Rhodophyta).
AB  - Species of the genus Mastocarpus exhibit two distinct life cycles, a sexual
      alternation of generations and an obligate, asexual direct life cycle that
      produces only female upright fronds. In the intertidal red alga, M. papillatus
      (Kutzing) sexual fronds dominate southern populations and asexual fronds dominate
      northern populations along the northeast Pacific coast, a pattern of spatial
      separation called geographic parthenogenesis. Along the central coast of
      California, sexual and asexual variants occur in mixed populations, but it is not
      known whether they are spatially separated within the intertidal zone at a given
      site. We investigated reproductive phenologies and analyzed patterns of spatial
      distributions of sexual and asexual M. papillatus at three sites in this region.
      Sexual M. papillatus were aggregated lower on the shore at two sites and only
      reproduced during part of a year, while asexual M. papillatus occurred throughout
      the intertidal range at all sites and reproduced throughout the year. The
      distribution patterns of sexual and asexual M. papillatus are consistent with a
      hypothesis of shoreline topography influencing their dynamics of dispersal and
      colonization. Spatial and temporal partitioning may contribute to the long-term
      coexistence of sexual and asexual life histories in this, and other, species of
      Mastocarpus. The occurrence of geographic parthenogenesis at multiple spatial
      scales in M. papillatus provides an opportunity to gain insight into the
      phenomenon.

PMID- 20802794
TI  - Bacteriophage Bundles with Pre-Aligned Ca Initiate the Oriented Nucleation and
      Growth of Hydroxylapatite.
AB  - Inorganic ions may direct the self-assembly of biomacromolecules into
      nanostructures which can further be used as a reactant and matrix for
      nanomaterials synthesis and assembly. Here we use bone mineral and filamentous
      bacteriophage as a model to demonstrate this concept. Divalent calcium ions are
      found to trigger the electrostatic self-assembly of anionic nanofiber-like
      bacteriophages into bundle structures where calcium ions are pre-organized
      between bacteriophage nanofibers. The resultant Ca(2+)-bacteriophage bundles can
      be separated and purified from the aqueous solution. The nanostructures of the
      bundles are verified by zeta potential analysis, small angle x-ray scattering and
      transmission electron microscopy. Because of the transcription of the
      bacteriophage chiral surface to the periodic alignment of pre-loaded Ca(2+), the
      Ca(2+)-bacteriphage bundles can serve as both Ca sources and biotemplates to
      initiate the oriented nucleation and growth of nanocrystalline hydroxyapatite in
      phosphate solution or in simulated body fluid. This work provides new insights
      into biomineralization and represents a new approach to the fabrication of
      biomolecular-inorganic hybrid layered nanostructures.

PMID- 20802793
TI  - Altered cholesterol and fatty acid metabolism in Huntington disease.
AB  - Huntington disease is an autosomal dominant neurodegenerative disorder
      characterized by behavioral abnormalities, cognitive decline, and involuntary
      movements that lead to a progressive decline in functional capacity,
      independence, and ultimately death. The pathophysiology of Huntington disease is
      linked to an expanded trinucleotide repeat of cytosine-adenine-guanine (CAG) in
      the IT-15 gene on chromosome 4. There is no disease-modifying treatment for
      Huntington disease, and novel pathophysiological insights and therapeutic
      strategies are needed. Lipids are vital to the health of the central nervous
      system, and research in animals and humans has revealed that cholesterol
      metabolism is disrupted in Huntington disease. This lipid dysregulation has been
      linked to specific actions of the mutant huntingtin on sterol regulatory element
      binding proteins. This results in lower cholesterol levels in affected areas of
      the brain with evidence that this depletion is pathologic. Huntington disease is
      also associated with a pattern of insulin resistance characterized by a catabolic
      state resulting in weight loss and a lower body mass index than individuals
      without Huntington disease. Insulin resistance appears to act as a metabolic
      stressor attending disease progression. The fish-derived omega-3 fatty acids,
      eicosapentaenoic acid and docosahexaenoic acid, have been examined in clinical
      trials of Huntington disease patients. Drugs that combat the dysregulated lipid
      milieu in Huntington disease may help treat this perplexing and catastrophic
      genetic disease.

PMID- 20802795
TI  - ADOLESCENT WORK INTENSITY, SCHOOL PERFORMANCE, AND ACADEMIC ENGAGEMENT.
AB  - Teenagers working over 20 hours per week perform worse in school than youth who
      work less. There are two competing explanations for this association: (1) that
      paid work takes time and effort away from activities that promote achievement,
      such as completing homework, preparing for examinations, getting help from
      parents and teachers, and participating in extracurricular activities; and (2)
      that the relationship between paid work and school performance is spurious,
      reflecting preexisting differences between students in academic ability,
      motivation, and school commitment. Using longitudinal data from the ongoing
      national Monitoring the Future project, this research examines the impact of
      teenage employment on school performance and academic engagement during the 8th,
      10th, and 12th grades. We address issues of spuriousness by using a two-level
      hierarchical model to estimate the relationships of within-individual changes in
      paid work to changes in school performance and other school-related measures.
      Unlike prior research, we also compare youth school performance and academic
      orientation when they are actually working in high-intensity jobs to when they
      are jobless and wish to work intensively. Results indicate that the mere wish for
      intensive work corresponds with academic difficulties in a manner similar to
      actual intensive work.

PMID- 20802796
TI  - Judgments about Work and the Features of Young Adults' Jobs.
AB  - This study revisits the relationship between adolescent judgments about work and
      later job characteristics, tackling the twin temporal dimensions of age and
      history. Drawing on 15 consecutive cohorts of high school seniors, we examine 1)
      whether adolescents' judgments about work become more strongly predictive of the
      characteristics of their jobs as they move through their twenties, and 2) whether
      the relationship between adolescents' judgments about work and their later job
      characteristics has weakened across cohorts of high school seniors between 1976
      and 1990. Findings indicate a limited role of history; the larger life course
      story of these findings is tied to age. Adolescent judgments about work, measured
      in the senior year of high school, became more predictive of earnings with age
      during this period of the life course. They were also most predictive of the
      level of intrinsic job characteristics at the oldest age we examined, but the
      pattern was not one of progressive strengthening with age as it was for earnings.

PMID- 20802797
TI  - Efficient Suzuki and Stille Reactions for Regioselective Strategies of
      Incorporation of the 1,3-Oxazole Heterocycle. Mild Desulfonylation for the
      Synthesis of C-4 and C-5 Monosubstituted Oxazoles.
AB  - Suzuki and Stille cross-coupling reactions are surveyed for site-selective C-4
      and C-5 elaboration of 2-(phenylsulfonyl)-1,3-oxazole derivatives. Conditions for
      mild reductive desulfonylations provide for direct incorporation of the intact
      oxazole heterocycle through bonding at C-4 and C-5.

PMID- 20802799
TI  - The Sleep of the Bereaved.
AB  - OBJECTIVE: Sleep disruption is common in widow(er)s. The objective of this study
      was to characterize the sleep of Spousally Bereaved (SB) seniors (60y+) studied
      within 4-19 months of being widowed. METHOD: Subjective (PSQI, 2-weeks diary) and
      objective (2-weeks actigraphy) baseline sleep measures were obtained in 47 (38f,
      9m) Spousally Bereaved (SB) seniors, 33 (25f, 8m) Good Sleeper Controls (GSC),
      and 47 (38f, 9m) Older Adults with Insomnia (OAI); each group with the same mean
      age (72y). OAI subjects passed formal diagnostic criteria for primary or co
      morbid insomnia. GSC subjects had no diagnosis of insomnia. At baseline (pre
      treatment), all subjects completed 2 weeks of detailed sleep diary and wrist
      actigraphy, and completed the Pittsburgh Sleep Quality Index (PSQI) among other
      measures. RESULTS: Significant group effects appeared in PSQI (GSC: 2.4, SB: 6.7,
      OAI: 10.5; Effect Sizes [ES]>1) and diary measures. In diary measures, for Total
      Sleep Time, Sleep Efficiency and Wake After Sleep Onset, SB were better than OAI
      and worse than GSC (0.47<ES<1.19). For Sleep Latency, SB were worse than GSC
      (ES=0.57), but similar to OAI. However, actigraphy results indicated no
      significant SB vs. GSC, or SB vs. OAI, differences in any of the sleep measures
      considered. CONCLUSION: The sleep disruption of bereaved seniors appears to be
      intermediate between GSC and OAI, as reported either retrospectively using the
      PSQI, or prospectively using a sleep diary. Only in diary sleep latency, were SB
      and OAI values similar. This pattern was not, however, observed when parallel
      objective actigraphic measures were considered.

PMID- 20802798
TI  - PI(3,5)P(2) controls membrane trafficking by direct activation of mucolipin
      Ca(2+) release channels in the endolysosome.
AB  - Membrane fusion and fission events in intracellular trafficking are controlled by
      both intraluminal Ca(2+) release and phosphoinositide (PIP) signalling. However,
      the molecular identities of the Ca(2+) release channels and the target proteins
      of PIPs are elusive. In this paper, by direct patch-clamping of the endolysosomal
      membrane, we report that PI(3,5)P(2), an endolysosome-specific PIP, binds and
      activates endolysosome-localized mucolipin transient receptor potential (TRPML)
      channels with specificity and potency. Both PI(3,5)P(2)-deficient cells and cells
      that lack TRPML1 exhibited enlarged endolysosomes/vacuoles and trafficking
      defects in the late endocytic pathway. We find that the enlarged vacuole
      phenotype observed in PI(3,5)P(2)-deficient mouse fibroblasts is suppressed by
      overexpression of TRPML1. Notably, this PI(3,5)P(2)-dependent regulation of
      TRPML1 is evolutionarily conserved. In budding yeast, hyperosmotic stress induces
      Ca(2+) release from the vacuole. In this study, we show that this release
      requires both PI(3,5)P(2) production and a yeast functional TRPML homologue. We
      propose that TRPMLs regulate membrane trafficking by transducing information
      regarding PI(3,5)P(2) levels into changes in juxtaorganellar Ca(2+), thereby
      triggering membrane fusion/fission events.

PMID- 20802801
TI  - Statistical phylogenetic tree analysis using differences of means.
AB  - We propose a statistical method to test whether two phylogenetic trees with given
      alignments are significantly incongruent. Our method compares the two
      distributions of phylogenetic trees given by two input alignments, instead of
      comparing point estimations of trees. This statistical approach can be applied to
      gene tree analysis for example, detecting unusual events in genome evolution such
      as horizontal gene transfer and reshuffling. Our method uses difference of means
      to compare two distributions of trees, after mapping trees into a vector space.
      Bootstrapping alignment columns can then be applied to obtain p-values. To
      compute distances between means, we employ a "kernel method" which speeds up
      distance calculations when trees are mapped in a high-dimensional feature space,
      e.g., splits or quartets feature space. In this pilot study, first we test our
      statistical method on data sets simulated under a coalescence model, to test
      whether two alignments are generated by congruent gene trees. We follow our
      simulation results with applications to data sets of gophers and lice, grasses
      and their endophytes, and different fungal genes from the same genome. A
      companion toolkit, Phylotree, is provided to facilitate computational
      experiments.

PMID- 20802802
TI  - Htr2a Gene and 5-HT(2A) Receptor Expression in the Cerebral Cortex Studied Using
      Genetically Modified Mice.
AB  - Serotonin receptors of the 5-HT(2A) subtype are robustly expressed in the
      cerebral cortex where they have been implicated in the pathophysiology and
      therapeutics of mental disorders and the actions of hallucinogens. Much less is
      known, however, about the specific cell types expressing 5-HT(2A) receptors in
      cortex. In the current study we use immunohistochemical and electrophysiological
      approaches in genetically modified mice to address the expression of the Htr2a
      gene and 5-HT(2A) receptors in cortex. We first use an EGFP-expressing BAC
      transgenic mice and identify three main Htr2A gene expressing neuronal
      populations in cortex. The largest of these cell populations corresponds to layer
      V pyramidal cells of the anterior cortex, followed by GABAergic interneurons of
      the middle layers, and non-pyramidal cells of the subplate/Layer VIb. We then use
      5-HT(2A) receptor knockout mice to identify an antibody capable of localizing 5
      HT(2A) receptors in brain and use it to map these receptors. We find strong
      laminar expression of 5-HT(2A) receptors in cortex, especially along a diffuse
      band overlaying layer Va. This band exhibits a strong anteroposterior gradient
      that closely matches the localization of Htr2A expressing pyramidal cells of
      layer V. Finally we use electrophysiological and immunohistochemical approaches
      to show that most, but not all, GABAergic interneurons of the middle layers are
      parvalbumin expressing Fast-spiking interneurons and that these cells are
      depolarized and excited by serotonin, most likely through the activation of 5
      HT(2A) receptors. These results clarify and extend our understanding of the
      cellular distribution of 5-HT(2A) receptors in the cerebral cortex.

PMID- 20802800
TI  - Neural Protein Synthesis during Aging: Effects on Plasticity and Memory.
AB  - During aging, many experience a decline in cognitive function that includes
      memory loss. The encoding of long-term memories depends on new protein synthesis,
      and this is also reduced during aging. Thus, it is possible that changes in the
      regulation of protein synthesis contribute to the memory impairments observed in
      older animals. Several lines of evidence support this hypothesis. For instance,
      protein synthesis is required for a longer period following learning to establish
      long-term memory in aged rodents. Also, under some conditions, synaptic activity
      or pharmacological activation can induce de novo protein synthesis and lasting
      changes in synaptic transmission in aged, but not young, rodents; the opposite
      results can be observed in other conditions. These changes in plasticity likely
      play a role in manifesting the altered place field properties observed in awake
      and behaving aged rats. The collective evidence suggests a link between memory
      loss and the regulation of protein synthesis in senescence. In fact,
      pharmaceuticals that target the signaling pathways required for induction of
      protein synthesis have improved memory, synaptic plasticity, and place cell
      properties in aged animals. We suggest that a better understanding of the
      mechanisms that lead to different protein expression patterns in the neural
      circuits that change as a function of age will enable the development of more
      effective therapeutic treatments for memory loss.

PMID- 20802804
TI  - Exercise as an intervention for the age-related decline in neural metabolic
      support.
AB  - To identify interventions for brain aging, we must first identify the processes
      in which we hope to intervene. Brain aging is a period of decreasing functional
      capacity and increasing vulnerability, which reflect a reduction in morphological
      organization and perhaps degeneration. Since life is ultimately dependent upon
      the ability to maintain cellular organization through metabolism, this review
      explores evidence for a decline in neural metabolic support during aging, which
      includes a reduction in whole brain cerebral blood flow, and cellular metabolic
      capacity. Capillary density may also decrease with age, although the results are
      less clear. Exercise may be a highly effective intervention for brain aging,
      because it improves the cardiovascular system as a whole, and increases regional
      capillary density and neuronal metabolic capacity. Although the evidence is
      strongest for motor regions, more work may yield additional evidence for exercise
      related improvement in metabolic support in non-motor regions. The protective
      effects of exercise may be specific to brain region and the type of insult. For
      example, exercise protects striatal cells from ischemia, but it produces mixed
      results after hippocampal seizures. Exercise can improve metabolic support and
      bioenergetic capacity in adult animals, but it remains to be determined whether
      it has similar effects in aging animals. What is clear is that exercise can
      influence the multiple levels of support necessary for maintaining optimal
      neuronal function, which is unique among proposed interventions for aging.

PMID- 20802803
TI  - Vascular tone and neurovascular coupling: considerations toward an improved in
      vitro model.
AB  - Neurovascular research has made significant strides toward understanding how the
      brain neurovascular unit accomplishes rapid and spatial increases in blood flow
      following neuronal activation. Among the experimental models used, the in vitro
      brain slice preparation provides unique information revealing the potential
      signals and cellular mechanisms involved in functional hyperemia. The most
      crucial limitation of this model, however, is the lack of intraluminal pressure
      and flow in the vessels being studied. Moreover, differences in basal vascular
      tone have led to varied interpretations regarding the polarity of vascular
      responses following neuron-to-glial stimulation. Given the complexity of
      astrocyte-induced neurovascular responses, we propose the use of a modified in
      vitro brain slice preparation, where intraluminal arteriolar pressure and flow
      are retained. Throughout this review, we discuss the advantages and disadvantages
      to be considered when using brain slices for neurovascular studies. Potential
      ways to overcome the current limitations are proposed.

PMID- 20802805
TI  - Evaluation of spatial anisotropy by curvature analysis of elliptical targets.
AB  - Spatial relationship perception (SRP), defined as the function able to detect the
      difference between the perceived extent of a shape along the x/y cardinal
      coordinates, has been investigated in 42 eyes of 21 emmetropic subjects by means
      of a psychophysical test conceived on purpose. Aiming to the highest sensibility
      and since curvature detection is reckoned as an hyperacuity, elliptical stimuli
      have been chosen to measure the spatial relationship anisotropy (SRA) in the
      visual system. Observers turned out to be able to detect curvature differences
      along the elliptical contour as low as 33.6 sec arc, which in terms of SRP means
      an aspect ratio (i.e. the ratio between the height and the width of the ellipse)
      as low as 1.0022-1.0035. By comparing these results with those obtained in
      previous investigations from other curvature discrimination tasks, it is argued
      that recognition threshold is conditioned by the amount of space anisotropy of
      the visual system. Indeed, in about half of the recruited subjects,
      vertical/horizontal anisotropy is found to a certain extent and such SRA
      correlates with the recognition threshold (r= 0.69, p<0.01). There is direct
      evidence of visual spatial distortion and in particular increased anisotropy in
      neuro-ophtalmological diseases such as hemianopia and around scotomatous regions
      in the visual field. Thence, apart from theoretical considerations in
      physiological field, results collected in this study may be regarded as normative
      data for future clinical investigations.

PMID- 20802806
TI  - Do Patients with Obstructive Sleep Apnea have an Increased Risk of Desaturation
      During Induction of Anesthesia for Weight Loss Surgery?
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is an independent risk factor to
      develop perioperative complications during weight loss surgery, but the
      mechanisms are unclear. It is possible, that patients with OSA have a higher
      incidence of desaturation during induction of anesthesia. METHODS: We enrolled
      100 morbidly obese (body mass index: 53+/-10) adult patients undergoing open
      bariatric surgery in a prospective study. At least 1 h before induction of
      anesthesia, peripheral oxygen saturation (SpO(2)) was measured by an oximetry
      finger probe in the sitting and supine positions, and Mallampati score was taken.
      Oxygen saturation was recorded also during induction of anesthesia, and nadir
      values were analyzed, and the STOP-BANG questionnaire was applied. RESULTS:
      Thirty-six patients presented with clinical suspicion of OSA. Body weight
      predicted oxygen saturation in the supine and sitting position, prior to
      induction of anesthesia. Nadir oxygen saturation during induction of anesthesia
      was considerably higher in patients with clinical suspicion of OSA, a significant
      finding that persisted as a trend after correction for age, gender and BMI. The
      Mallampati score was an independent predictor of OSA, even in morbidly obese
      patients scheduled for weight loss surgery. CONCLUSIONS: Morbidly obese patients
      presenting for weight loss surgery have a significant risk to desaturate during
      induction of anesthesia. A history of OSA does not independently increase the
      risk of desaturation during induction of anesthesia, if the appropriate
      precautions are being taken.

PMID- 20802807
TI  - Gender, division of unpaid family work and psychological distress in dual-earner
      families.
AB  - INTRODUCTION: Epidemiological studies have only recently begun to address the
      consequences of unpaid family work (ie., housework and child rearing) for mental
      health. Although research is suggestive of an association between the division of
      unpaid family work and psychological health, especially for women, additional
      research is required to clarify the conditions under which such a relationship
      holds. The purpose of the present study was to examine more nuanced relationships
      between the division of family work and psychological distress by disaggregating
      the family work construct according to type (housework/child rearing), control
      over scheduling, and evaluations of fairness. METHODS: Analysis of data obtained
      from a cross-sectional telephone survey conducted in a Canadian city. Analyses
      were based on 293 employed parents (182 mothers and 111 fathers), with at least
      one preschool child, living in dual-earner households. Several multiple linear
      regression models were estimated with psychological distress as the outcome,
      adjusting for confounders. RESULTS: For mothers, more perceived time spent in
      child rearing (particularly primary child care) and high-schedule-control
      housework tasks (e.g. yard work) relative to one's partner, were associated with
      greater distress. For fathers, perceived unfairness in the division of housework
      and child rearing were associated with greater distress. CONCLUSION: Although
      methodological limitations temper firm conclusions, these results suggest that
      the gendered nature of household work has implications for the psychological well
      being of both mothers and fathers of preschool children in dual-earner
      households. However, more longitudinal research and the development of
      theoretically-informed measures of family work are needed to advance the field.

PMID- 20802808
TI  - First-visit diagnosis of preperimetric glaucoma.
AB  - PURPOSE: To present a revised interpretation of the work-up data that enabled
      diagnosis of preperimetric glaucoma (PPG) at the first examination. METHODS: a)
      Literature analysis on PPG; b) 6-year follow-up of a glaucoma-suspect patient.
      RESULTS: TWO NEW CONCEPTS MAY BE ADAPTED: (a) the objective finding of retinal
      nerve fiber layer (RNFL) thinning below the normal border in the opposing typical
      glaucoma locations, the inferior and superior quadrants, and in a non-diffuse
      pattern, appears asymptomatically and simultaneously only in glaucoma; and (b)
      the imaging-related RNFL thickness may be considered the reference glaucoma
      standard, whereas the suspicious early glaucomatous optic neuropathy, having a
      potential diagnostic inaccuracy, would serve as a complementary revealing
      finding. That approach enabled, in retrospect, a first-visit diagnosis of low
      tension PPG in the patient. Diagnosis was confirmed after 6 years, when
      cecocentral scotoma and further RNFL thinning emerged despite treatment.
      CONCLUSIONS: A revised approach enabled PPG diagnosis during the first visit.

PMID- 20802810
TI  - Protocol: influence of budesonide and budesonide/formoterol on asthma control in
      smoking asthmatic adults.
AB  - RATIONALE: A reduced response to inhaled corticosteroids (ICS) has been reported
      in smoking asthmatic patients but the effects of other medications remain to be
      evaluated in this population. SUBJECTS AND METHODS: We evaluated the effects of a
      combined therapy of budesonide 200 microg twice daily and formoterol 6 microg
      twice daily compared with budesonide 200 microg twice daily alone on asthma
      control questionnaire (ACQ), asthma quality of life questionnaire (AQLQ-
      Juniper), pulmonary function and airway inflammation, in a cross-over randomized
      double-blind study with treatment periods of two months separated by a one-month
      wash-out period. Seventeen smoking and 22 non-smoking patients not using inhaled
      corticosteroids with slightly uncontrolled mild asthma completed the study.
      RESULTS: ACQ and AQLQ scores were similar in both groups at baseline and improved
      similarly after treatments. beta2-agonist use was higher in smokers, regardless
      of the treatment received (p=0.03), as it was on baseline (p=0.003). Smokers
      treated with budesonide/formoterol showed an increase in the number of asthma
      episodes (intercurrent asthma symptoms, p=0.016) while non-smoking subjects had a
      significant decrease in these episodes (p=0.009). No difference was found between
      smokers and non-smokers in regard to post-treatment airway inflammatory
      parameters. CONCLUSIONS: No significant differences were found between smoking
      and non-smoking subjects with mild asthma in regard to clinical changes in asthma
      control, pulmonary function and airway inflammation following a 2-month treatment
      period with budesonide or the association of budesonide and formoterol for a
      period of 2 months. This should be further explored in larger groups of subjects.

PMID- 20802809
TI  - Animal models of ischemic stroke. Part one: modeling risk factors.
AB  - Ischemic stroke is one of the leading causes of long-term disability and death in
      developed and developing countries. As emerging disease, stroke related mortality
      and morbidity is going to step up in the next decades. This is both due to the
      poor identification of risk factors and persistence of unhealthy habits, as well
      as to the aging of the population. To counteract the estimated increase in stroke
      incidence, it is of primary importance to identify risk factors, study their
      effects, to promote primary and secondary prevention, and to extend the
      therapeutic repertoire that is currently limited to the very first hours after
      stroke. While epidemiologic studies in the human population are essential to
      identify emerging risk factors, adequate animal models represent a fundamental
      tool to dissect stroke risk factors to their molecular mechanism and to find
      efficacious therapeutic strategies for this complex multi- factorial disorder.
      The present review is organized into two parts: the first part deals with the
      animal models that have been developed to study stroke and its related risk
      factors and the second part analyzes the specific stroke models. These models
      represent an indispensable tool to investigate the mechanisms of cerebral injury
      and to develop novel therapies.

PMID- 20802811
TI  - Regulation of Human MUC7 Mucin Gene Expression by Cigarette Smoke Extract or
      Cigarette Smoke and Pseudomonas aeruginosa Lipopolysaccharide in Human Airway
      Epithelial Cells and in MUC7 Transgenic Mice.
AB  - OBJECTIVE: The human MUC7 gene encodes a low-molecular-weight mucin glycoprotein
      that functions in lubrication/protection of epithelial surfaces of the oral
      cavity and respiratory tract. This study was designed to evaluate the effect of
      cigarette smoke extract (CSE), cigarette smoke (CS), and Pseudomonas aeruginosa
      lipopolysaccharide (LPS), either alone or in the combination, on MUC7 expression
      in vitro and in vivo. MATERIALS AND METHODS: qRT-PCR was used to determine the
      levels of mucin gene transcription in the human lung carcinoma cell line NCI-H292
      (in vitro) and MUC7 transgenic mouse tissues (in vivo). ELISA was used to assess
      mucin glycoprotein levels in the cell line, and immunohistochemistry to assess
      mucins in lung and trachea sections. RESULTS: In vitro treatment of cells with
      LPS (10 (microg/ml) or CSE (0.5, 1, 2.5 and 5%) alone, resulted in a
      statistically significant increase of MUC7 transcripts only with 1%CSE (3.2
      fold). The combined CSE/LPS treatment resulted in a synergistic increase of MUC7
      with 0.5%CSE/LPS (4.4 fold). MUC7 glycoprotein levels increased only minimally,
      the highest increase was seen with the 0.5%CSE/LPS combination treatment (1.3
      fold). In vivo exposure of MUC7 transgenic mice to CS, LPS or CS/LPS combination
      resulted in significant increase in MUC7 transcripts only with LPS treatment (in
      both trachea and lung). Immunohistochemistry indicated variable increase in MUC7
      glycoprotein with CS and LPS treatment, both in the trachea and lungs, but CS/LPS
      exposure appeared to yield the highest increase. CONCLUSION: In vitro, CSE and a
      combination of CSE/LPS treatment upregulated MUC7 gene transcription. In vivo,
      LPS upregulated MUC7 transcription, and a combination of CS/LPS appeared to
      increase MUC7 glycoprotein.

PMID- 20802812
TI  - Further Electrochemical and Behavioural Evidence of a Direct Relationship Between
      Central 5-HT and Cytoskeleton in the Control of Mood.
AB  - Reduced activity of CNS serotonin is reported in unipolar depression and
      serotonin is the major target of recent antidepressant drugs. However, an acute
      depletion of serotonin in healthy individuals does not induce depressive symptoms
      suggesting that depression does not correlate with the serotonin system only.
      Neuronal plasticity (structural adaptation of neurons to functional requirements)
      includes synthesis of microtubular proteins such as tyrosinated isoform of alpha
      tubulin and presence of serotonin as regulator of synaptogenesis. In depression
      neuronal plasticity is modified.HERE, IN RATS SUBMITTED TO A BEHAVIOURAL TEST
      WIDELY USED TO PREDICT THE EFFICACY OF ANTIDEPRESSANT DRUGS (FORCED SWIMMING
      TEST: FST) a significant decrease of both cerebral tyrosinated alpha-tubulin
      expression and serotonin levels is monitored. Moreover, treatment with para
      chlorophenylalanine (PCPA, compound that specifically depletes brain serotonin)
      but not alpha-methyl para tyrosine (alpha-MPT, compound that blocks synthesis of
      catechols: chemicals also implicated in depression) significantly reduced
      tyrosinated alpha-tubulin. Thus, a direct relationship between serotonin and
      tyrosinated alpha-tubulin appears to be present both in "physiological" and in
      "pathological" states. In addition, data obtained in animals submitted to FST
      and/or treated with the selective serotonin reuptake inhibitor (SSRI) fluoxetine
      further support the interrelationship between central serotonin and cytoskeleton.
      These data propose that direct relationship between serotonin and tyrosinated
      alpha-tubulin could be considered within the mechanism(s) involved in the
      pathogenesis of depression.

PMID- 20802813
TI  - Standardized Observational Assessment of Attention Deficit Hyperactivity Disorder
      Combined and Predominantly Inattentive Subtypes. II. Classroom Observations.
AB  - Trained classroom observers used the Direct Observation Form (DOF; McConaughy &
      Achenbach, 2009) to rate observations of 163 6- to 11-year-old children in their
      school classrooms. Participants were assigned to four groups based on a parent
      diagnostic interview and parent and teacher rating scales: Attention Deficit
      Hyperactivity Disorder (ADHD)-Combined type (n = 64); ADHD-Inattentive type (n =
      22); clinically referred without ADHD (n = 51); and nonreferred control children
      (n = 26). The ADHD-Combined group scored significantly higher than the referred
      without ADHD group and controls on the DOF Intrusive and Oppositional syndromes,
      Attention Deficit Hyperactivity Problems scale, Hyperactivity-Impulsivity
      subscale, and Total Problems; and significantly lower on the DOF On-Task score.
      The ADHD-Inattentive group scored significantly higher than controls on the DOF
      Sluggish Cognitive Tempo and Attention Problems syndromes, Inattention subscale,
      and Total Problems; and significantly lower on the DOF On-Task score.
      Implications are discussed regarding the discriminative validity of standardized
      classroom observations for identifying children with ADHD and differentiating
      between the two ADHD subtypes.

PMID- 20802814
TI  - Standardized Observational Assessment of Attention Deficit Hyperactivity Disorder
      Combined and Predominantly Inattentive Subtypes. I. Test Session Observations.
AB  - Test examiners used the Test Observation Form (McConaughy & Achenbach, 2004) to
      rate test session behavior of 177 6- to 11-year-old children during
      administration of the Wechsler Intelligence Scale for Children-Fourth Edition
      (WISC-IV) and Wechsler Individual Achievement Tests-Second Edition (WIAT-II).
      Participants were assigned to four groups based on a parent diagnostic interview
      and parent and teacher rating scales: attention deficit hyperactivity disorder
      (ADHD)-Combined type (n = 74); ADHD-Inattentive type (n = 25); clinically
      referred without ADHD (n = 52); and controls (n = 26). The ADHD-Combined type
      group scored significantly higher than the other three groups on six Test
      Observation Form scales: (1) Attention Problems; (2) Oppositional; (3) Attention
      Deficit/Hyperactivity Problems scale; (4) Inattention sub-scale; (5)
      Hyperactivity-Impulsivity subscale; and (6) Externalizing. The two ADHD groups
      also scored significantly lower than controls on all WISC-IV and WIAT-II
      composites and lower than those clinically referred without ADHD on WISC-IV
      Working Memory Index and Full Scale Intelligence Quotient. Implications are
      discussed regarding the discriminative validity of standardized test session
      observations for identifying children with ADHD and differentiating between the
      two ADHD subtypes.

PMID- 20802815
TI  - Repair of a complete anterior cruciate tear using prolotherapy: a case report.
AB  - OBJECTIVE AND IMPORTANCE: Surgical reconstruction is considered definitive
      treatment for anterior cruciate ligament (ACL) tears but precise surgical
      indications are debated. Some patients are reluctant or inappropriate surgical
      candidates. Prolotherapy is a non-surgical injection therapy for chronic
      musculoskeletal pain and instability. This case report documents the non-surgical
      repair of a torn ACL using prolotherapy and at-home exercise. CLINICAL
      PRESENTATION AND INTERVENTION: The 18 year old female patient sustained a right
      knee injury during a downhill skiing accident. Magnetic Resonance Imaging (MRI)
      revealed a high-grade partial versus complete rupture; Lachman exam findings
      suggested a complete rupture. She deferred surgical treatment. At 21 weeks post
      injury, with unstable gait, inability to climb stairs and more than 1 cm anterior
      drawer test, she consented to undergo prolotherapy injections. She received 7
      prolotherapy sessions over a 15 week period. At-home exercises were initiated at
      the 3(rd) prolotherapy session. RESULTS: The patient improved. Walking on flat
      ground improved 4 weeks after initiation of prolotherapy; she could ride a
      stationary bicycle for 30 minutes by 12 weeks. By 15 weeks, the patient had no
      instability climbing and descending stairs, the anterior drawer test was negative
      and MRI showed an intact ACL with fibrosis. Subsequently, she returned to full
      sport activity. CONCLUSIONS: We document the non-surgical repair of a high-grade
      partial or complete ACL tear using prolotherapy and at-home exercise.
      Prolotherapy may be an alternative to surgery in carefully selected patients.
      This report is consistent with findings of recent pilot-level studies and
      suggests the need for rigorous clinical trials assessing prolotherapy as
      treatment for ligament and tendon injury in selected patients.

PMID- 20802816
TI  - Synchronization as a mechanism for attentional gain modulation.
AB  - Responses of neurons in monkey visual cortex are modulated when attention is
      directed into the receptive field of the neuron: the gain or sensitivity of the
      response is increased or the synchronization of the spikes to the local field
      potential (LFP) is increased. We investigated, using model simulations, whether
      the synchrony of inhibitory networks could link these observations. We found
      that, indeed, an increase in inhibitory synchrony could enhance the coherence of
      the model neurons with the simulated LFP, and could have different effects on the
      firing rate. When the firing rate vs. current (f-I) response curves saturated at
      high I, attention yielded a shift in sensitivity; alternatively, when the f-I
      curves were non-saturating, the most significant effect was on the gain of the
      response. This suggests that attention may act through changes in the synchrony
      of inhibitory networks.

PMID- 20802817
TI  - Synthesis and Characterization of High Integrity Solid-Contact Polymeric Ion
      Sensors.
AB  - High integrity solid-contact (SC) polymeric ion sensors have been produced by
      using spin casting and electropolymerization techniques in the preparation of the
      SC employing the conductive polymer, poly(3-octylthiophene) [POT]. The physical
      and chemical integrity of the POT SCs have been evaluated using scanning electron
      microscopy (SEM), atomic force microscopy (AFM), secondary ion mass spectrometry
      (SIMS) and X-ray photoelectron spectroscopy (XPS). Furthermore, the
      electrochemical stability of SC polymeric ion sensors has been investigated using
      electrochemical impedance spectroscopy (EIS). The results of this study
      demonstrate that electropolymerization and spin casting methods also comprising
      annealing of the synthesized SC film are capable of producing SCs that are
      relatively free of imperfections such as pores and pinholes. This leads to
      electrochemically stable and robust polymeric ion sensors where the SC/sensor
      interface is resistant to the formation of a detrimental water layer that
      normally gives rise to spurious ion fluxes and a degradation in the sensitivity
      and selectivity of the SC polymeric ion sensor.

PMID- 20802818
TI  - Rating Movies and Rating the Raters Who Rate Them.
AB  - The movie distribution company Netflix has generated considerable buzz in the
      statistics community by offering a million dollar prize for improvements to its
      movie rating system. Among the statisticians and computer scientists who have
      disclosed their techniques, the emphasis has been on machine learning approaches.
      This article has the modest goal of discussing a simple model for movie rating
      and other forms of democratic rating. Because the model involves a large number
      of parameters, it is nontrivial to carry out maximum likelihood estimation. Here
      we derive a straightforward EM algorithm from the perspective of the more general
      MM algorithm. The algorithm is capable of finding the global maximum on a
      likelihood landscape littered with inferior modes. We apply two variants of the
      model to a dataset from the MovieLens archive and compare their results. Our
      model identifies quirky raters, redefines the raw rankings, and permits
      imputation of missing ratings. The model is intended to stimulate discussion and
      development of better theory rather than to win the prize. It has the added
      benefit of introducing readers to some of the issues connected with analyzing
      high-dimensional data.

PMID- 20802819
TI  - Dolabra nepheliae on rambutan and lychee represents a novel lineage of
      phytopathogenic Eurotiomycetes.
AB  - Rambutan (Nephelium lappaceum) and lychee (Litchi chinensis) are tropical trees
      in the Sapindaceae that produce delicious edible fruits and are increasingly
      cultivated in tropical regions. These trees are afflicted with a stem canker
      disease associated with the ascomycete Dolabra nepheliae. Previously known from
      Asia and Australia, this fungus was recently reported from Hawaii and Puerto
      Rico. The sexual and asexual states of Dolabra nepheliae are redescribed and
      illustrated. In addition, the ITS and large subunit of the nuclear ribosomal DNA
      plus fragments from the genes RPB2, TEF1, and the mitochondrial small ribosomal
      subunit were sequenced for three isolates of D. nepheliae and compared with other
      sequences of ascomycetes. It was determined that D. nepheliae represents a new
      lineage within the Eurotiomycetes allied with Phaeomoniella chlamydospora, the
      causal agent of Petri grapevine decline.

PMID- 20802820
TI  - Prediction of inter-residue contact clusters from hydrophobic cores.
AB  - A contact map is a key factor representing a specific protein structure. To
      simplify the protein contact map prediction, we predict the inter-residue contact
      clusters centered at the groups of their surrounding inter-residue contacts. In
      this paper, we adopt a Support Vector Machine (SVM)-based approach to predict the
      inter-residue contact cluster centers. The input of the SVM predictor includes
      sequence profile, evolutionary rate and predicted secondary structure. The SVM
      predictor is based on hydrophobic cores that may be considered as locations of
      the inter-residue contact clusters. About 35% of clustering centers of inter
      residue contacts can be predicted accurately.

PMID- 20802821
TI  - Information Integration from Semantically Heterogeneous Biological Data Sources.
AB  - We present the first prototype of INDUS (Intelligent Data Understanding System),
      a federated, query-centric system for information integration and knowledge
      acquisition from distributed, semantically heterogeneous data sources that can be
      viewed (conceptually) as tables. INDUS employs ontologies and inter-ontology
      mappings, to enable a user to view a collection of such data sources (regardless
      of location, internal structure and query interfaces) as though they were a
      collection of tables structured according to an ontology supplied by the user.
      This allows INDUS to answer user queries against distributed, semantically
      heterogeneous data sources without the need for a centralized data warehouse or a
      common global ontology.

PMID- 20802822
TI  - ?
AB  - Este articulo reporta un estudio realizado en las ciudades de La Paz, Cochabamba,
      y Santa Cruz en Bolivia. Interesaba saber cual era la situacion de la bioetica en
      Bolivia y como se estaba protegiendo a los sujetos de investigacion.Luego de
      revisar algunos conceptos bioeticos, la legislacion boliviana y los metodos del
      estudio, se dan a conocer los resultados del mismo, los cuales revelan gran
      desconocimiento respecto de como proteger los derechos de los sujetos, por la
      casi ausencia o el inadecuado funcionamiento de los comites de etica de la
      investigacion.

PMID- 20802823
TI  - On Estimation of Partially Linear Transformation Models.
AB  - We study a general class of partially linear transformation models, which extend
      linear transformation models by incorporating nonlinear covariate effects in
      survival data analysis. A new martingale-based estimating equation approach,
      consisting of both global and kernel-weighted local estimation equations, is
      developed for estimating the parametric and nonparametric covariate effects in a
      unified manner. We show that with a proper choice of the kernel bandwidth
      parameter, one can obtain the consistent and asymptotically normal parameter
      estimates for the linear effects. Asymptotic properties of the estimated
      nonlinear effects are established as well. We further suggest a simple resampling
      method to estimate the asymptotic variance of the linear estimates and show its
      effectiveness. To facilitate the implementation of the new procedure, an
      iterative algorithm is developed. Numerical examples are given to illustrate the
      finite-sample performance of the procedure.

PMID- 20802824
TI  - Robust stimulation of humoral and cellular immune responses following vaccination
      with antigen-loaded beta-glucan particles.
AB  - beta-Glucan particles (GPs) are purified Saccharomyces cerevisiae cell walls
      treated so that they are primarily beta1,3-d-glucans and free of mannans and
      proteins. GPs are phagocytosed by dendritic cells (DCs) via the Dectin-1
      receptor, and this interaction stimulates proinflammatory cytokine secretion by
      DCs. As the hollow, porous GP structure allows for high antigen loading, we
      hypothesized that antigen-loaded GPs could be exploited as a receptor-targeted
      vaccine delivery system. Ovalbumin (OVA) was electrostatically complexed inside
      the hollow GP shells (GP-OVA). Incubation of C57BL/6J mouse bone marrow-derived
      DCs with GP-OVA resulted in phagocytosis, upregulation of maturation markers, and
      rapid proteolysis of OVA. Compared with free OVA, GP-OVA was >100-fold more
      potent at stimulating the proliferation of OVA-reactive transgenic CD8(+) OT-I
      and CD4(+) OT-II T cells, as measured by in vitro [(3)H]thymidine incorporation
      using DCs as antigen-presenting cells. Next, immune responses in C57BL/6J mice
      following subcutaneous immunizations with GP-OVA were compared with those in
      C57BL/6J mice following subcutaneous immunizations with OVA absorbed onto the
      adjuvant alum (Alum/OVA). Vaccination with GP-OVA stimulated substantially higher
      antigen-specific CD4(+) T-cell lymphoproliferative and enzyme-linked immunospot
      (ELISPOT) responses than that with Alum/OVA. Moreover, the T-cell responses
      induced by GP-OVA were Th1 biased (determined by gamma interferon [IFN-gamma]
      ELISPOT assay) and Th17 biased (determined by interleukin-17a [IL-17a] ELISPOT
      assay). Finally, both the GP-OVA and Alum/OVA formulations induced strong
      secretions of IgG1 subclass anti-OVA antibodies, although only GP-OVA induced
      secretion of Th1-associated IgG2c antibodies. Thus, the GP-based vaccine platform
      combines adjuvanticity and antigen delivery to induce strong humoral and Th1- and
      Th17-biased CD4(+) T-cell responses.

PMID- 20802825
TI  - The Pseudomonas aeruginosa exopolysaccharide Psl facilitates surface adherence
      and NF-kappaB activation in A549 cells.
AB  - In order for the opportunistic Gram-negative pathogen Pseudomonas aeruginosa to
      cause an airway infection, the pathogen interacts with epithelial cells and the
      overlying mucous layer. We examined the contribution of the biofilm
      polysaccharide Psl to epithelial cell adherence and the impact of Psl on
      proinflammatory signaling by flagellin. Psl has been implicated in the initial
      attachment of P. aeruginosa to biotic and abiotic surfaces, but its direct role
      in pathogenesis has not been evaluated (L. Ma, K. D. Jackson, R. M. Landry, M. R.
      Parsek, and D. J. Wozniak, J. Bacteriol. 188:8213-8221, 2006). Using an NF-kappaB
      luciferase reporter system in the human epithelial cell line A549, we show that
      both Psl and flagellin are necessary for full activation of NF-kappaB and
      production of the interleukin 8 (IL-8) chemokine. We demonstrate that Psl does
      not directly stimulate NF-kappaB activity, but indirectly as a result of
      increasing contact between bacterial cells and epithelial cells, it facilitates
      flagellin-mediated proinflammatory signaling. We confirm differential adherence
      of Psl and/or flagellin mutants by scanning electron microscopy and identify Psl
      dependent membrane structures that may participate in adherence. Although we
      hypothesized that Psl would protect P. aeruginosa from recognition by the
      epithelial cell line A549, we instead observed a positive role for Psl in
      flagellin-mediated NF-kappaB activation, likely as a result of increasing contact
      between bacterial cells and epithelial cells.

PMID- 20802826
TI  - The combination of rifampin plus moxifloxacin is synergistic for suppression of
      resistance but antagonistic for cell kill of Mycobacterium tuberculosis as
      determined in a hollow-fiber infection model.
AB  - Moxifloxacin is under development for expanded use against Mycobacterium
      tuberculosis. Rifampin is a mainstay of therapy. We examined the interaction of
      moxifloxacin plus rifampin for log-phase and nonreplicating persister (NRP)
      organisms. For this evaluation, we employed our hollow-fiber infection model, in
      which organisms are exposed to clinically relevant drug concentration-time
      profiles and the impact on bacterial cell kill and resistant subpopulation
      amplification is determined. In log phase, resistance emergence was observed in
      all monotherapy regimens and in no combination therapy regimen. No difference was
      seen in time to a 3-log reduction in the bacterial burden; there was a
      significant difference in time to resistance emergence (P = 0.0006). In the NRP
      experiment, no resistance emergence was seen. There was a significant difference
      between the monotherapy and combination therapy regimens in time to a 3-log
      reduction in the bacterial burden (P = 0.042). The combination is efficacious for
      suppressing resistant organisms but is antagonistic for cell kill.

PMID- 20802827
TI  - Comparative analyses of the bacterial microbiota of the human nostril and
      oropharynx.
AB  - The nose and throat are important sites of pathogen colonization, yet the
      microbiota of both is relatively unexplored by culture-independent approaches. We
      examined the bacterial microbiota of the nostril and posterior wall of the
      oropharynx from seven healthy adults using two culture-independent methods, a 16S
      rRNA gene microarray (PhyloChip) and 16S rRNA gene clone libraries. While the
      bacterial microbiota of the oropharynx was richer than that of the nostril, the
      oropharyngeal microbiota varied less among participants than did nostril
      microbiota. A few phyla accounted for the majority of the bacteria detected at
      each site: Firmicutes and Actinobacteria in the nostril and Firmicutes,
      Proteobacteria, and Bacteroidetes in the oropharynx. Compared to culture
      independent surveys of microbiota from other body sites, the microbiota of the
      nostril and oropharynx show distinct phylum-level distribution patterns,
      supporting niche-specific colonization at discrete anatomical sites. In the
      nostril, the distribution of Actinobacteria and Firmicutes was reminiscent of
      that of skin, though Proteobacteria were much less prevalent. The distribution of
      Firmicutes, Proteobacteria, and Bacteroidetes in the oropharynx was most similar
      to that in saliva, with more Proteobacteria than in the distal esophagus or
      mouth. While Firmicutes were prevalent at both sites, distinct families within
      this phylum dominated numerically in each. At both sites there was an inverse
      correlation between the prevalences of Firmicutes and another phylum: in the
      oropharynx, Firmicutes and Proteobacteria, and in the nostril, Firmicutes and
      Actinobacteria. In the nostril, this inverse correlation existed between the
      Firmicutes family Staphylococcaceae and Actinobacteria families, suggesting
      potential antagonism between these groups.

PMID- 20802828
TI  - Inferring the evolutionary history of the plant pathogen Pseudomonas syringae
      from its biogeography in headwaters of rivers in North America, Europe, and New
      Zealand.
AB  - Nonhost environmental reservoirs of pathogens play key roles in their
      evolutionary ecology and in particular in the evolution of pathogenicity. In
      light of recent reports of the plant pathogen Pseudomonas syringae in pristine
      waters outside agricultural regions and its dissemination via the water cycle, we
      have examined the genetic and phenotypic diversity, population structure, and
      biogeography of P. syringae from headwaters of rivers on three continents and
      their phylogenetic relationship to strains from crops. A collection of 236
      strains from 11 sites in the United States, in France, and in New Zealand was
      characterized for genetic diversity based on housekeeping gene sequences and for
      phenotypic diversity based on measures of pathogenicity and ice nucleation
      activity. Phylogenetic analyses revealed several new genetic clades from water.
      The genetic structure of P. syringae populations was not influenced by geographic
      location or water chemistry, whereas the phenotypic structure was affected by
      these parameters. Comparison with strains from crops revealed that the
      metapopulation of P. syringae is structured into three genetic ecotypes: a crop
      specific type, a water-specific type, and an abundant ecotype found in both
      habitats. Aggressiveness of strains was significantly and positively correlated
      with ice nucleation activity. Furthermore, the ubiquitous genotypes were the most
      aggressive, on average. The abundance and diversity in water relative to crops
      suggest that adaptation to the freshwater habitat has played a nonnegligible role
      in the evolutionary history of P. syringae. We discuss how adaptation to the
      water cycle is linked to the epidemiological success of this plant pathogen.

PMID- 20802829
TI  - Indirect pathogenicity of Haemophilus influenzae and Moraxella catarrhalis in
      polymicrobial otitis media occurs via interspecies quorum signaling.
AB  - Otitis media (OM) is among the leading diseases of childhood and is caused by
      opportunists that reside within the nasopharynx, such as Haemophilus influenzae
      and Moraxella catarrhalis. As with most airway infections, it is now clear that
      OM infections involve multiple organisms. This study addresses the hypothesis
      that polymicrobial infection alters the course, severity, and/or treatability of
      OM disease. The results clearly show that coinfection with H. influenzae and M.
      catarrhalis promotes the increased resistance of biofilms to antibiotics and host
      clearance. Using H. influenzae mutants with known biofilm defects, these
      phenotypes were shown to relate to biofilm maturation and autoinducer-2 (AI-2)
      quorum signaling. In support of the latter mechanism, chemically synthesized AI-2
      (dihydroxypentanedione [DPD]) promoted increased M. catarrhalis biofilm formation
      and resistance to antibiotics. In the chinchilla infection model of OM,
      polymicrobial infection promoted M. catarrhalis persistence beyond the levels
      seen in animals infected with M. catarrhalis alone. Notably, no such enhancement
      of M. catarrhalis persistence was observed in animals infected with M.
      catarrhalis and a quorum signaling-deficient H. influenzae luxS mutant strain. We
      thus conclude that H. influenzae promotes M. catarrhalis persistence within
      polymicrobial biofilms via interspecies quorum signaling. AI-2 may therefore
      represent an ideal target for disruption of chronic polymicrobial infections.
      Moreover, these results strongly imply that successful vaccination against the
      unencapsulated H. influenzae strains that cause airway infections may also
      significantly impact chronic M. catarrhalis disease by removing a reservoir of
      the AI-2 signal that promotes M. catarrhalis persistence within biofilm.

PMID- 20802830
TI  - Effects of congenital heart disease on brain development.
AB  - Brain and heart development occurs simultaneously in the fetus with congenital
      heart disease. Early morphogenetic programs in each organ share common genetic
      pathways. Brain development occurs across a more protracted time-course with
      striking brain growth and activity-dependent formation and refinement of
      connections in the third trimester. This development is associated with increased
      metabolic activity and the brain is dependent upon the heart for oxygen and
      nutrient delivery. Congenital heart disease leads to derangements of fetal blood
      flow that result in impaired brain growth and development that can be measured
      with advanced magnetic resonance imaging. Delayed development results in a unique
      vulnerability to cerebral white matter injury in newborns with congenital heart
      disease. Delayed brain development and acquired white matter injury may underlay
      mild but pervasive neurodevelopmental impairment commonly observed in children
      following neonatal congenital heart surgery.

PMID- 20802831
TI  - Using Herbal Remedies to Maintain Optimal Weight.

PMID- 20802832
TI  - Integration of Diverse Research Methods to Analyze and Engineer Ca-Binding
      Proteins: From Prediction to Production.
AB  - In recent years, increasingly sophisticated computational and bioinformatics
      tools have evolved for the analyses of protein structure, function, ligand
      interactions, modeling and energetics. This includes the development of
      algorithms to recursively evaluate side-chain rotamer permutations, identify
      regions in a 3D structure that meet some set of search parameters, calculate and
      minimize energy values, and provide high-resolution visual tools for theoretical
      modeling. Here we discuss the interdependency between different areas of
      bioinformatics, the evolution of different algorithm design approaches, and
      finally the transition from theoretical models to real-world design and
      application as they relate to Ca(2+)-binding proteins. Within this context, it
      has become evident that significant pre-experimental design and calculations can
      be modeled through computational methods, thus eliminating potentially
      unproductive research and increasing our confidence in the correlation between
      real and theoretical models. Moving from prediction to production, it is
      anticipated that bioinformatics tools will play an increasingly significant role
      in research and development, improving our ability to both understand the
      physiological roles of Ca(2+) and other metals and to extend that knowledge to
      the design of function-specific synthetic proteins capable of fulfilling
      different roles in medical diagnostics and therapeutics.

PMID- 20802835
TI  - Microphase separation in copolymers of hydrophilic PEG blocks and hydrophobic
      tyrosine-derived segments using simultaneous SAXS/WAXS/DSC.
AB  - Hydration- and temperature-induced microphase separations were investigated by
      simultaneous small- and wide-angle X-ray scattering (SAXS and WAXS) and
      differential scanning calorimetry (DSC) in a family of copolymers in which
      hydrophilic poly(ethylene glycol) (PEG) blocks are inserted randomly into a
      hydrophobic polymer made of either desaminotyrosyl-tyrosine ethyl ester (DTE) or
      iodinated I(2)DTE segments. Iodination of the tyrosine rings in I(2)DTE increased
      the X-ray contrast between the hydrophobic and hydrophilic segments in addition
      to facilitating the study of the effect of iodination on microphase separation.
      The formation of phase-separated, hydrated PEG domains is of considerable
      significance as it profoundly affects the polymer properties. The copolymers of
      DTE (or I(2)DTE) and PEG are a useful model system and the findings presented
      here may be applicable to other PEG-containing random copolymers as well. In
      copolymers of PEG and DTE and I(2)DTE, the presence of PEG depressed the glass
      transition temperature (T(g)) of the copolymer relative to the homopolymer,
      poly(DTE carbonate), and the DTE/ I(2)DTE segments hindered the crystallization
      of the PEG segments. In the dry state, at large PEG fractions (> 70 vol%), the
      PEG domains self-assembled into an ordered structure with 14-18 nm distance
      between the domains. These domains gave rise to a SAXS peak at all temperatures
      in the iodinated polymers, but only above the T(g) in non-iodinated polymers, due
      to the unexpected contrast- match between the crystalline PEG domains and the
      glassy DTE segments. Irrespective of whether PEG was crystalline or not,
      immersion of these copolymers in water resulted in the formation of hydrated PEG
      domains that were 10-20 nm apart. Since both water and the polymer chains must be
      mobile for the phase separation to occur, the PEG domains disappeared when the
      water froze, and reappeared as the ice began to melt. This transformation was
      reversible, and showed hysteresis as did the melting of ice and freezing of the
      water incorporated into the polymer. PEG-water complexes and PEG-water eutectics
      were observed in WAXS and DSC scans, respectively.

PMID- 20802833
TI  - Disembodying cognition.
AB  - The idea that concepts are embodied by our motor and sensory systems is popular
      in current theorizing about cognition. Embodied cognition accounts come in
      different versions and are often contrasted with a purely symbolic amodal view of
      cognition. Simulation, or the hypothesis that concepts simulate the sensory and
      motor experience of real world encounters with instances of those concepts, has
      been prominent in psychology and cognitive neuroscience. Here, with a focus on
      spatial thought and language, I review some of the evidence cited in support of
      simulation versions of embodied cognition accounts. While these data are
      extremely interesting and many of the experiments are elegant, knowing how to
      best interpret the results is often far from clear. I point out that a quick
      acceptance of embodied accounts runs the danger of ignoring alternate hypotheses
      and not scrutinizing neuroscience data critically. I also review recent work from
      my lab that raises questions about the nature of sensory motor grounding in
      spatial thought and language. In my view, the question of whether or not
      cognition is grounded is more fruitfully replaced by questions about gradations
      in this grounding. A focus on disembodying cognition, or on graded grounding,
      opens the way to think about how humans abstract. Within neuroscience, I propose
      that three functional anatomic axes help frame questions about the graded nature
      of grounded cognition. First, are questions of laterality differences. Do
      association cortices in both hemispheres instantiate the same kind of sensory or
      motor information? Second, are questions about ventral dorsal axes. Do neuronal
      ensembles along this axis shift from conceptual representations of objects to the
      relationships between objects? Third, are questions about gradients centripetally
      from sensory and motor cortices towards and within perisylvian cortices. How does
      sensory and perceptual information become more language-like and then get
      transformed into language proper?

PMID- 20802834
TI  - The role of visual attention in multiple object tracking: evidence from ERPs.
AB  - We examined the role of visual attention in the multiple object tracking (MOT)
      task by measuring the amplitude of the N1 component of the event-related
      potential (ERP) to probe flashes presented on targets, distractors, or empty
      background areas. We found evidence that visual attention enhances targets and
      suppresses distractors (Experiment 1 & 3). However, we also found that when
      tracking load was light (two targets and two distractors), accurate tracking
      could be carried out without any apparent contribution from the visual attention
      system (Experiment 2). Our results suggest that attentional selection during MOT
      is flexibly determined by task demands as well as tracking load and that visual
      attention may not always be necessary for accurate tracking.

PMID- 20802836
TI  - Trust in Medical Technology by Patients and Health Care Providers in Obstetric
      Work Systems.
AB  - Multiple types of users (i.e. patients and care providers) have experiences with
      the same technologies in health care environments and may have different
      processes for developing trust in those technologies. The objective of this study
      was to assess how patients and care providers make decisions about the
      trustworthiness of mutually used medical technology in an obstetric work system.
      Using a grounded theory methodology, we conducted semi-structured interviews with
      25 patients who had recently given birth and 12 obstetric health care providers
      to examine the decision-making process for developing trust in technologies used
      in an obstetric work system. We expected the two user groups to have similar
      criteria for developing trust in the technologies, though we found patients and
      physicians differed in processes for developing trust. Trust in care providers,
      the technologies' characteristics and how care providers used technology were all
      related to trust in medical technology for the patient participant group.
      Trustworthiness of the system and trust in self were related to trust in medical
      technology for the physician participant group. Our findings show that users with
      different perspectives of the system have different criteria for developing trust
      in medical technologies.

PMID- 20802837
TI  - Too much noise in the Times Higher Education rankings.
AB  - Several individual indicators from the Times Higher Education Survey (THES) data
      base-the overall score, the reported staff-to-student ratio, and the peer ratings
      demonstrate unacceptably high fluctuation from year to year. The
      inappropriateness of the summary tabulations for assessing the majority of the
      "top 200" universities would be apparent purely for reason of this obvious
      statistical instability regardless of other grounds of criticism. There are far
      too many anomalies in the change scores of the various indices for them to be of
      use in the course of university management.

PMID- 20802838
TI  - Stereotype Embodiment: A Psychosocial Approach to Aging.
AB  - Researchers have increasingly turned their attention from younger individuals who
      hold age stereotypes to older individuals who are targeted by these stereotypes.
      The refocused research has shown that positive and negative age stereotypes held
      by older individuals can have beneficial and detrimental effects, respectively,
      on a variety of cognitive and physical outcomes. Drawing on these experimental
      and longitudinal studies, a theory of stereotype embodiment is presented here. It
      proposes that stereotypes are embodied when their assimilation from the
      surrounding culture leads to self-definitions that, in turn, influence
      functioning and health. The theory has four components: The stereotypes (a)
      become internalized across the life span, (b) can operate unconsciously, (c) gain
      salience from self-relevance, and (d) utilize multiple pathways. The central
      message of the theory, and the research supporting it, is that the aging process
      is, in part, a social construct.

PMID- 20802839
TI  - HARDI DATA DENOISING USING VECTORIAL TOTAL VARIATION AND LOGARITHMIC BARRIER.
AB  - In this work, we wish to denoise HARDI (High Angular Resolution Diffusion
      Imaging) data arising in medical brain imaging. Diffusion imaging is a relatively
      new and powerful method to measure the three-dimensional profile of water
      diffusion at each point in the brain. These images can be used to reconstruct
      fiber directions and pathways in the living brain, providing detailed maps of
      fiber integrity and connectivity. HARDI data is a powerful new extension of
      diffusion imaging, which goes beyond the diffusion tensor imaging (DTI) model:
      mathematically, intensity data is given at every voxel and at any direction on
      the sphere. Unfortunately, HARDI data is usually highly contaminated with noise,
      depending on the b-value which is a tuning parameter pre-selected to collect the
      data. Larger b-values help to collect more accurate information in terms of
      measuring diffusivity, but more noise is generated by many factors as well. So
      large b-values are preferred, if we can satisfactorily reduce the noise without
      losing the data structure. Here we propose two variational methods to denoise
      HARDI data. The first one directly denoises the collected data S, while the
      second one denoises the so-called sADC (spherical Apparent Diffusion
      Coefficient), a field of radial functions derived from the data. These two
      quantities are related by an equation of the form S = S(S)exp (-b . sADC) (in the
      noise-free case). By applying these two different models, we will be able to
      determine which quantity will most accurately preserve data structure after
      denoising. The theoretical analysis of the proposed models is presented, together
      with experimental results and comparisons for denoising synthetic and real HARDI
      data.

PMID- 20802841
TI  - Concise Preparation of Novel Tricyclic Chemotypes: Fused Hydantoin
      benzodiazepines.
AB  - The following article describes a concise synthesis of a collection of 4,5
      dihydro-1H-benzo[e][1,4]diazepines fused to a hydantoin ring. Molecular
      complexity and biological relevance is high and structures are generated in a
      mere three steps, employing the Ugi reaction to assemble diversity reagents. The
      protocol represents a novel UDC (Ugi-deprotect-cyclize) strategy employed in the
      Ugi-5-component CO(2) mediated condensation, followed by further cyclization
      under basic conditions, to afford the fused hydantoin. Mechanistic caveats,
      dependent on aldehydes of choice will be revealed and a facile oxidation of final
      products to imidazolidenetriones briefly discussed.

PMID- 20802840
TI  - The Impact of Illness Identity on Recovery from Severe Mental Illness.
AB  - The impact of the experience and diagnosis of mental illness on one's identity
      has long been recognized; however, little is known about the impact of illness
      identity, which we define as the set of roles and attitudes that a person has
      developed in relation to his or her understanding of having a mental illness. The
      present article proposes a theoretically driven model of the impact of illness
      identity on the course and recovery from severe mental illness and reviews
      relevant research. We propose that accepting a definition of oneself as mentally
      ill and assuming that mental illness means incompetence and inadequacy impact
      hope and self-esteem, which further impact suicide risk, coping, social
      interaction, vocational functioning, and symptom severity. Evidence supports most
      of the predictions made by the model. Implications for psychiatric rehabilitation
      services are discussed.

PMID- 20802842
TI  - Genetic content of Influenza H3N2 vaccine seeds.
AB  - Influenza vaccine seeds produced in chicken eggs are selected through HA and NA
      surface glycoproteins antigenicity, as well as through high replicative ability.
      Here we characterize the genetic content of recently used thirteen H3N2 influenza
      vaccine seeds. Interestingly, sequence analysis of the vaccine seeds shows
      reassortment events leading to PR8:H3N2 segment constellations, ranging from the
      6:2 to 2:6 constellations. This study shows that the H3N2 PB1 is the most
      frequent internal segment incorporated in the tested vaccines seeds.

PMID- 20802843
TI  - Many Faces of Openness in Adoption: Perspectives of Adopted Adolescents and Their
      Parents.
AB  - Parents and adolescents (mean age, 15.7 years) from 177 adoptive families
      participating in the second wave of the Minnesota/Texas Adoption Research Project
      were interviewed about their post-adoption contact arrangements. The sample
      included families with no contact, stopped contact, contact without meetings, and
      contact with face-to-face meetings between the adolescent and birth mother.
      Openness arrangements were dynamic, and different openness arrangements were
      associated with different experiences and feelings. Adoptive families with
      contact reported having higher levels of satisfaction about their openness
      arrangements, experiencing more positive feelings about the birth mother, and
      possessing more factual and personal knowledge about the birth mother than did
      families without contact. Adolescents and adoptive mothers in the contact with
      meetings group reported the greatest satisfaction with their openness
      arrangements; those with no contact or stopped contact reported the least
      satisfaction with their arrangements. Participants having no contact were more
      likely to want the intensity of contact to increase in the future rather than
      stay the same. Many participants already having contact wanted it to increase in
      the future. Fewer than 1 percent of all participants wanted to see the intensity
      of contact decrease.

PMID- 20802845
TI  - Cross-linguistic Differences in Talking About Scenes.
AB  - Speakers of English and Tamil differ widely in which relational roles they
      overtly express with a verb. This study provides new information about how
      speakers of these languages differ in their descriptions of the same scenes and
      how explicit mention of roles and other scene elements vary with the properties
      of the scenes themselves. Specifically, we find that English speakers, who in
      normal speech rely more on explicit mention of verb arguments, in fact appear to
      be more affected by the pragmatic manipulations used in this study than Tamil
      speakers. Additionally, although the mention of scene items increases with
      development in both languages, Tamil-speaking children mention fewer items than
      do English-speaking children, showing that the children know the structure of the
      language to which they are exposed.

PMID- 20802844
TI  - The Impact of Continued Contact with Biological Parents upon the Mental Health of
      Children in Foster Care.
AB  - This study examined depression and externalizing problems of children in foster
      care using a subsample of data (N = 362) from the National Survey of Child and
      Adolescent Well-Being. Our findings indicated that more frequent contact with the
      biological mother was marginally associated with lower levels depression and
      significantly associated with lower externalizing problem behaviors. The
      association with externalizing problem behavior was significant even after
      controlling for gender and exposure to violence. Further, differences with regard
      to gender were revealed. Specifically, girls had higher depression scores than
      boys even after controlling for exposure to violence. Results suggest that
      supporting frequent, consistent, visitation may impact the levels of depression
      and externalizing programs children in foster care exhibit.

PMID- 20802847
TI  - Delinquency and alcohol-impaired driving among young males: A longitudinal study.
AB  - The present study assessed how the trajectory of delinquency affects the growth
      curve of alcohol-impaired driving using three-waves of data collected from the
      Buffalo Longitudinal Survey of Young Men (BLSYM). Using the structural equation
      modeling method, latent growth modeling was utilized to assess four age cohorts
      of sixteen, seventeen, eighteen, and nineteen years of age at the first wave. The
      data indicated that the growth rate of delinquency significantly and positively
      affects the growth rate of alcohol-impaired driving for the respondents who were
      sixteen at the first wave. The growth rate of drinking was also significantly and
      positively associated with the growth rate of alcohol-impaired driving for this
      age cohort. Although the growth rate of delinquency had no significant effect on
      the growth rate of alcohol-impaired driving for the age cohort which was
      seventeen at Wave 1, the growth rates of both drinking and drug use did affect
      for this age cohort. The data, however, showed that alcohol-impaired driving had
      a significant increase across the waves for the eighteen year old cohort, but
      there was no significant variation in the rate across respondents. Finally, for
      the nineteen year old cohort there was no significant increase in alcohol
      impaired driving across the waves, and also no significant variation of the
      growth rate of alcohol-impaired driving across the respondents. These findings
      indicated that interventions focused on reducing delinquency, alcohol and drug
      use by sixteen and seventeen year old male adolescents will also reduce their
      alcohol-impaired driving.

PMID- 20802846
TI  - Neuroprotection in Pediatric Cardiac Surgery: What is On the Horizon?

PMID- 20802849
TI  - Eradication of Pathogenic Bacteria by Remote Delivery of Nitric Oxide via Light
      Triggering of Nitrosyl-Containing Materials.
AB  - Although nitric oxide (NO) delivery systems have been fabricated with sol-gel
      based materials, remote control of such systems with light has not been achieved.
      In this work, a fiber optic-based NO delivery system is described in which the
      photoactive metal-nitrosyl, [Mn(PaPy(3))(NO)]ClO(4) (1), has been employed in a
      sol-gel material. The material (1*FO) contains the manganese-nitrosyl which
      releases NO upon illumination with visible light. The NO-releasing capacity of
      1*FO has been measured with an NO-sensitive electrode and the spatial diffusion
      of NO in solution has been visualized using the Griess reaction. The utility of
      1*FO has been demonstrated in effective reduction of bacterial loads of
      Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and methicillin
      resistant Staphylococcus aureus (MRSA). The results suggest that a device that
      releases NO via illumination by optical fiber may have clinical applications in
      combating infections with both Gram-positive, Gram-negative and to some degree
      antibiotic resistant bacteria.

PMID- 20802848
TI  - PROTEIN TEMPLATES IN HARD TISSUE ENGINEERING.
AB  - Biomineralization processes such as formation of bones and teeth require
      controlled mineral deposition and self-assembly into hierarchical biocomposites
      with unique mechanical properties. Ideal biomaterials for regeneration and repair
      of hard tissues must be biocompatible, possess micro and macroporosity for
      vascular invasion, provide surface chemistry and texture that facilitate cell
      attachment, proliferation, differentiation of lineage specific progenitor cells,
      and induce deposition of calcium phosphate mineral. To expect in-vivo like
      cellular response several investigators have used extracellular matrix proteins
      as templates to recreate in-vivo microenvironment for regeneration of hard
      tissues. Recently, several novel methods of designing tissue repair and
      restoration materials using bioinspired strategies are currently being
      formulated. Nanoscale structured materials can be fabricated via the spontaneous
      organization of self-assembling proteins to construct hierarchically organized
      nanomaterials. The advantage of such a method is that polypeptides can be
      specifically designed as building blocks incorporated with molecular recognition
      features and spatially distributed bioactive ligands that would provide a
      physiological environment for cells in-vitro and in-vivo. This is a rapidly
      evolving area and provides a promising platform for future development of
      nanostructured templates for hard tissue engineering. In this review we try to
      highlight the importance of proteins as templates for regeneration and repair of
      hard tissues as well as the potential of peptide based nanomaterials for
      regenerative therapies.

PMID- 20802850
TI  - Preliminary Examination of Adolescent Spending in a Contingency Management Based
      Smoking Cessation Program.
AB  - Contingency management (CM) utilizing monetary incentives is efficacious in
      enhancing abstinence in an adolescent smoking cessation program, but how
      adolescents spend their money has not been examined. We assessed spending habits
      of 38 adolescent smokers in a CM-based smoking cessation project prior to
      quitting and during treatment using a questionnaire about spending in a number of
      categories, including cigarettes, other addictive substances, durable goods, and
      disposable goods. Our preliminary results indicate that participation in a CM
      based program for smoking cessation did not lead to greater spending on
      cigarettes and other substances and may have produced more socially acceptable
      spending.

PMID- 20802851
TI  - Real-Time Decision Making and Aggressive Behavior in Youth: A Heuristic Model of
      Response Evaluation and Decision (RED).
AB  - Considerable scientific and intervention attention has been paid to judgment and
      decision-making systems associated with aggressive behavior in youth. However,
      most empirical studies have investigated social-cognitive correlates of stable
      child and adolescent aggressiveness, and less is known about real-time decision
      making to engage in aggressive behavior. A model of real-time decision making
      must incorporate both impulsive actions and rational thought. The present paper
      advances a process model (response evaluation and decision; RED) of real-time
      behavioral judgments and decision making in aggressive youths with mathematic
      representations that may be used to quantify response strength. These components
      are a heuristic to describe decision making, though it is doubtful that
      individuals always mentally complete these steps. RED represents an organization
      of social-cognitive operations believed to be active during the response decision
      step of social information processing. The model posits that RED processes can be
      circumvented through impulsive responding. This article provides a description
      and integration of thoughtful, rational decision making and nonrational
      impulsivity in aggressive behavioral interactions.

PMID- 20802852
TI  - ASSESSING THE ASSOCIATION BETWEEN TRENDS IN A BIOMARKER AND RISK OF EVENT WITH AN
      APPLICATION IN PEDIATRIC HIV/AIDS.
AB  - We present a new joint longitudinal and survival model aimed at estimating the
      association between the risk of an event and the change in and history of a
      biomarker that is repeatedly measured over time. We use cubic B-splines models
      for the longitudinal component that lend themselves to straight-forward
      formulations of the slope and integral of the trajectory of the biomarker. The
      model is applied to data collected in a long term follow-up study of HIV infected
      infants in Uganda. Estimation is carried out using MCMC methods. We also explore
      using the deviance information criteria, the conditional predictive ordinate and
      ROC curves for model selection and evaluation.

PMID- 20802853
TI  - PENALIZED VARIABLE SELECTION PROCEDURE FOR COX MODELS WITH SEMIPARAMETRIC
      RELATIVE RISK.
AB  - We study the Cox models with semiparametric relative risk, which can be partially
      linear with one nonparametric component, or multiple additive or nonadditive
      nonparametric components. A penalized partial likelihood procedure is proposed to
      simultaneously estimate the parameters and select variables for both the
      parametric and the nonparametric parts. Two penalties are applied sequentially.
      The first penalty, governing the smoothness of the multivariate nonlinear
      covariate effect function, provides a smoothing spline ANOVA framework that is
      exploited to derive an empirical model selection tool for the nonparametric part.
      The second penalty, either the smoothly-clipped-absolute-deviation (SCAD) penalty
      or the adaptive LASSO penalty, achieves variable selection in the parametric
      part. We show that the resulting estimator of the parametric part possesses the
      oracle property, and that the estimator of the nonparametric part achieves the
      optimal rate of convergence. The proposed procedures are shown to work well in
      simulation experiments, and then applied to a real data example on sexually
      transmitted diseases.

PMID- 20802854
TI  - Optical mapping of release properties in synapses.
AB  - Synapses are important functional units that determine how information flows
      through the brain. Understanding their biophysical properties and the molecules
      that underpin them is an important goal of cellular neuroscience. Thus, it is of
      interest to develop protocols that allow easy measurement of synaptic parameters
      in model systems that permit molecular manipulations. Here, we used a sensitive
      and high-time resolution optical approach that allowed us to characterize two
      functional parameters critical to presynaptic efficacy: vesicle fusion
      probability (Pv) and readily-releasable pool size (RRP). We implemented two
      different approaches to determine the RRP size that were in broad agreement:
      depletion of the RRP by high-frequency stimulation and saturation of the calcium
      sensor during single action potential stimuli. Our methods are based on reporters
      that provide a robust, quantitative, purely presynaptic readout and present a new
      avenue to study molecules that affect synaptic vesicle exocytosis.

PMID- 20802855
TI  - A spiking neural network model of the medial superior olive using spike timing
      dependent plasticity for sound localization.
AB  - Sound localization can be defined as the ability to identify the position of an
      input sound source and is considered a powerful aspect of mammalian perception.
      For low frequency sounds, i.e., in the range 270 Hz-1.5 KHz, the mammalian
      auditory pathway achieves this by extracting the Interaural Time Difference
      between sound signals being received by the left and right ear. This processing
      is performed in a region of the brain known as the Medial Superior Olive (MSO).
      This paper presents a Spiking Neural Network (SNN) based model of the MSO. The
      network model is trained using the Spike Timing Dependent Plasticity learning
      rule using experimentally observed Head Related Transfer Function data in an
      adult domestic cat. The results presented demonstrate how the proposed SNN model
      is able to perform sound localization with an accuracy of 91.82% when an error
      tolerance of +/-10 degrees is used. For angular resolutions down to 2.5 degrees ,
      it will be demonstrated how software based simulations of the model incur
      significant computation times. The paper thus also addresses preliminary
      implementation on a Field Programmable Gate Array based hardware platform to
      accelerate system performance.

PMID- 20802856
TI  - Distinct superficial and deep laminar domains of activity in the visual cortex
      during rest and stimulation.
AB  - Spatial patterns of spontaneous neural activity at rest have previously been
      associated with specific networks in the brain, including those pertaining to the
      functional architecture of the primary visual cortex (V1). However, despite the
      prominent anatomical differences between cortical layers, little is known about
      the laminar pattern of spontaneous activity in V1. We address this topic by
      investigating the amplitude and coherence of ongoing local field potential (LFP)
      signals measured from different layers in V1 of macaque monkeys during rest and
      upon presentation of a visual stimulus. We used a linear microelectrode array to
      measure LFP signals at multiple, evenly spaced positions throughout the cortical
      thickness. Analyzing both the mean LFP amplitudes and between-contact LFP
      coherences, we identified two distinct zones of activity, roughly corresponding
      to superficial and deep layers, divided by a sharp transition near the bottom of
      layer 4. The LFP signals within each laminar zone were highly coherent, whereas
      those between zones were not. This functional compartmentalization was found not
      only during rest, but also when the receptive field was stimulated during a
      visual task. These results demonstrate the existence of distinct superficial and
      deep functional domains of coherent LFP activity in V1 that may reflect the
      intrinsic interplay of V1 microcircuitry with cortical and subcortical targets,
      respectively.

PMID- 20802857
TI  - AA/12-Lipoxygenase Signaling Contributes to Inhibitory Learning in Hermissenda
      Type B Photoreceptors.
AB  - Conditioned inhibition (CI) is a major category of associative learning that
      occurs when an organism learns that one stimulus predicts the absence of another.
      In addition to being important in its own right, CI is interesting because its
      occurrence implies that the organism has formed an association between stimuli
      that are non-coincident. In contrast to other categories of associative learning
      that are dependent upon temporal contiguity (pairings) of stimuli, the
      neurobiology of CI is virtually unexplored. We have previously described a simple
      form of CI learning in Hermissenda, whereby animals' phototactic behavior is
      increased by repeated exposures to explicitly unpaired (EU) presentations of
      light and rotation. EU conditioning also produces characteristic reductions in
      the excitability and light response, and increases several somatic K(+) currents
      in Type B photoreceptors. Type B photoreceptors are a major site of plasticity
      for classical conditioning in Hermissenda. Because arachidonic acid (AA) and/or
      its metabolites open diverse K(+) channels in many cell types, we examined the
      potential contribution of AA to CI. Our results indicate that AA contributes to
      one of the major effects of EU-conditioning on Type B photoreceptors: decreases
      in light-evoked spike activity. We find that AA increases the transient (I(A))
      somatic K(+) current in Type B photoreceptors, further mimicking CI training. In
      addition, our results indicate that metabolism of AA by a 12-lipoxygenase enzyme
      is critical for these effects of AA, and further that 12-lipoxygenase metabolites
      are apparently generated during CI training.

PMID- 20802858
TI  - Vasotocin actions on electric behavior: interspecific, seasonal, and social
      context-dependent differences.
AB  - Social behavior diversity is correlated with distinctively distributed patterns
      of a conserved brain network, which depend on the action of neuroendocrine
      messengers that integrate extrinsic and intrinsic cues. Arginine vasotocin (AVT)
      is a key integrator underlying differences in behavior across vertebrate taxa.
      Weakly electric fish use their electric organ discharges (EODs) as social
      behavioral displays. We examined the effect of AVT on EOD rate in two species of
      Gymnotiformes with different social strategies: Gymnotus omarorum, territorial
      and highly aggressive, and Brachyhypopomus gauderio, gregarious and aggressive
      only between breeding males. AVT induced a long-lasting and progressive increase
      of EOD rate in isolated B. gauderio, partially blocked by the V1a AVT receptor
      antagonist (Manning compound, MC), and had no effects in G. omarorum. AVT also
      induced a long-lasting increase in the firing rate (prevented by MC) of the
      isolated medullary pacemaker nucleus (PN) of B. gauderio when tested in an in
      vitro preparation, indicating that the PN is the direct effector of AVT actions.
      AVT is involved in the seasonal, social context-dependent nocturnal increase of
      EOD rate that has been recently described in B. gauderio to play a role in mate
      selection. AVT produced the additional nocturnal increase of EOD rate in non
      breeding males, whereas MC blocked it in breeding males. Also, AVT induced a
      larger EOD rate increase in reproductive dyads than in agonistic encounters. We
      demonstrated interspecific, seasonal, and context-dependent actions of AVT on the
      PN that contribute to the understanding of the mechanisms the brain uses to shape
      sociality.

PMID- 20802859
TI  - STDP in Oscillatory Recurrent Networks: Theoretical Conditions for
      Desynchronization and Applications to Deep Brain Stimulation.
AB  - Highly synchronized neural networks can be the source of various pathologies such
      as Parkinson's disease or essential tremor. Therefore, it is crucial to better
      understand the dynamics of such networks and the conditions under which a high
      level of synchronization can be observed. One of the key factors that influences
      the level of synchronization is the type of learning rule that governs synaptic
      plasticity. Most of the existing work on synchronization in recurrent networks
      with synaptic plasticity are based on numerical simulations and there is a clear
      lack of a theoretical framework for studying the effects of various synaptic
      plasticity rules. In this paper we derive analytically the conditions for spike
      timing dependent plasticity (STDP) to lead a network into a synchronized or a
      desynchronized state. We also show that under appropriate conditions bistability
      occurs in recurrent networks governed by STDP. Indeed, a pathological regime with
      strong connections and therefore strong synchronized activity, as well as a
      physiological regime with weaker connections and lower levels of synchronization
      are found to coexist. Furthermore, we show that with appropriate stimulation, the
      network dynamics can be pushed to the low synchronization stable state. This type
      of therapeutical stimulation is very different from the existing high-frequency
      stimulation for deep brain stimulation since once the stimulation is stopped the
      network stays in the low synchronization regime.

PMID- 20802860
TI  - [Planning and management in health: historical and tendencies based on a
      communicative view].
AB  - This article aims to present a condensed overview of major trends in Brazil,
      establish a general taxonomy of models of health management and planning, based
      on the international scene and support the proposal for a communicative planning.
      In a context of democratization,argues for a pluralistic conception and concludes
      that the various currents, albeit with different perspectives and referrals
      theoretical and methodological dialogue in a process of mutual exchange and
      learning.

PMID- 20802862
TI  - [Strategic management of hospitals in France: balance and perspectives].
AB  - The strategic management was introduced in French hospitals in the late 80s, in a
      context of inefficiency and the need to control healthcare expenditure. This
      concept has inspired a series of government reforms, the organization and
      dynamics of hospitals and the mode of regulating the French health system,
      assuming a real change of professional culture. The changes in the economic
      context and in the finance of hospitals, the behavior of users, the population
      aging, the development of chronic diseases and increased competition, are the new
      challenges to be faced. The involvement of stakeholders is crucial and the
      strategic management, based on mobilizing these actors, is today, a method of
      administration particularly well adapted to the health area. This article aims to
      present the impact of the concept of strategic management in the evolution of
      French hospitals and the consequences of these developments on the outlook for
      the dissemination of strategic management in the health sector. To do so, it is
      examined the evolution of the French context until 2010, the new challenges that
      French hospitals must face and, finally, the consequences of these challenges on
      how to design services, manage the relationships between the actors of the health
      system and organize the operational functioning of hospitals.

PMID- 20802863
TI  - [Health care networks].
AB  - The demographic and epidemiologic transition resulting from aging and the
      increase of life expectation means an increment related to chronic conditions.
      The healthcare systems contemporary crisis is characterized by the organization
      of the focus on fragmented systems turned to the acute conditions care, in spite
      of the chronic conditions prevalence, and by the hierarchical structure without
      communication flow among the different health care levels. Brazil health care
      situation profile is now presenting a triple burden of diseases, due to the
      concomitant presence of infectious diseases, external causes and chronic
      diseases. The solution is to restore the consistence between the triple burden of
      diseases on the health situation and the current system of healthcare practice,
      with the implantation of health care networks. The conclusion is that there are
      evidences in the international literature on health care networks that these
      networks may improve the clinical quality, the sanitation results and the user's
      satisfaction and the reduction of healthcare systems costs.

PMID- 20802864
TI  - [Health care networks: contextualizing the debate].
AB  - The proposal of organization in health services networks has been included in the
      broad field of integrated health care, a general denomination which includes a
      wide range of interventions varying in objectives and scope, which have in common
      the pursuit of integration strategies and tools. Among the main experiences in
      the field are the American integrated delivery systems and the traditional
      regionalized networks of the national health systems, especially after the
      introduction of new cooperation strategies. However, while strategies and
      organizational arrangements might be similar, context is central to debate. Not
      considering differences concerning health systems nature may turn it difficult to
      grasp main distinctions in policy making which are responsible for possibilities
      and limitations of adopting integration strategies and tools. This article aims
      to look for references in the literature and international experience that might
      contribute to the debate on health networks building in the Brazilian Unified
      Health System (SUS). It discusses context regarding the creation of integrated
      health services networks in two cases, the British National Health Service and
      the American Health System, focusing specifically on the health services
      organization component.

PMID- 20802865
TI  - [Structural conditions for regionalization in health care: typology of Regional
      Management Boards].
AB  - An explanation is required for the delay in implementing the regionalization
      strategy and the fragile nature of the combined decentralization and
      regionalization initiatives in Brazil. The article raises some hypotheses to
      clarify this intricate issue and reviews the structural conditioning factors of
      the regionalization process ongoing in the states. A national typology of the
      health care regions is prepared, differentiating them according to the degree of
      socio-economic development and the characteristics of the health care network and
      of the municipalities that form the Regional Management Boards (CGR), formally
      implanted by January 2010. Factorial and cluster analysis models were used to
      build the typology. Five major socio-economic groups of CGRs were identified,
      described according to their regional distribution, population, health care
      spending, profile of services offered (including the public-private sector mix)
      and health service coverage. The results obtained serve as guidelines for the
      constitution of health care networks and new initiatives at the regional level,
      in order to improve the regionalization policy and favour the construction of
      diverse and flexible regulatory instruments that are more in tune with the
      regional state of affairs.

PMID- 20802866
TI  - [(Re)visiting some elements of the situational approach: a critical examination
      of some of Carlos Matus's contributions].
AB  - Throughout his work, Carlos Matus offered a number of theoretical and
      methodological contributions to planning. Among them, I emphasize the
      understanding of planning as a way of calculation that precedes and presides over
      the action, the notion of situation, self-reported to the social actor who plans
      the importance of explanatory procedures and the so-called directional
      calculation. From a pragmatic reading of science and some contributions by
      Giddens, this paper examines the theoretical assumptions underlying these
      contributions. Specifically recognizing the importance of such contributions, it
      is a reading that radicalizes the self-reporting character, rejecting the claims
      of constructing a general theory of situational changes, focusing on the ability
      of social actors themselves to systematize the calculation that precedes and
      presides over the action from its own repertoire of interpretation. It explores
      the possibility of understanding the contributions of systematic and explicit
      calculation that precedes and guides the action as a way of expanding the
      theoretical understanding of the actions supported by human agents. Finally, we
      indicate the practical consequences of this (re)reading.

PMID- 20802867
TI  - [Democratic management and new craft: concepts to rethink integration between
      autonomy and responsibility in health work].
AB  - This article analyses tensions between the dominant management rationality and
      health work. By means of philosophical concepts and bibliography revision it was
      found that clinical and public health practices are structured as praxis, a term
      defined by Aristotle. It does not work automatically, depending on a human being
      to reflect and decide in most situations, making mediation between established
      knowledge and singular context. So, it is recommended the adoption of a
      management model that enables and favors the combination of professional autonomy
      and sanitary responsibility.

PMID- 20802868
TI  - [Subjectiveness and management: exploring psychosocial links on managerial and
      health work].
AB  - This paper presents our theoretical perspective over health management,
      particularly on managerial and health work. To face the complex problems related
      to public health services management and health care quality - important
      challenges of Brazilian Sanitary Reform - we study the group/inter-subjective and
      unconscious characteristic of organizational processes, which has important
      effects over health services dynamics and their quality. For this purpose, we
      attempt to articulate three theoretical perspectives:(1) the French Psycho
      sociology approach on organizations and contemporary society; (2) the
      psychoanalytical theory on inter-subjective and group processes; and (3) the Work
      Psychodynamics, which focuses the relations between pleasure and suffering in
      work processes. Through this research process, we explore links and mediations
      among psychic, inter-subjective, group and social realities that are present in
      health organizations, managerial work and health work. Also, limits and
      possibilities these mediations set to leadership, cooperation, collective
      projects and health care quality are identified.

PMID- 20802869
TI  - [Challenges for human resources management from successful experiences of Family
      Health Strategy expansion].
AB  - This article discusses the management of the work in Family Health Strategy in
      four major urban centers. The research includes perspectives from different
      actors who compose and integrate the network of working relationships in Public
      Health System through questionnaires with employees of professional categories
      family health team and interviews with managers and representatives of
      professional bodies. It is a qualitative-quantitative evaluation study. The
      dimensions analysed were: insertion and remuneration policies, strategies and
      qualification of employees. The insertion and remuneration policy highlights the
      replacement of outsourced frames and hiring by public tender that allows links
      labor more stable. Other strategies are the establishment of allowance for
      expertise in areas of greater social vulnerability and the assimilation of
      specialists in Family and Community Medicine with other experts engaged in
      secondary services. The political will of municipal Manager to qualify the
      workforce of family health, maintaining the provision of adequate human resources
      needs of the health system is a fundamental factor for the consolidation of
      family health strategy in the face of the low degree of specialization of
      professionals to work in primary health care.

PMID- 20802870
TI  - [National planning of health policy in Brazil: strategies and instruments in the
      2000s].
AB  - This paper discusses the national planning of health policy between 2003 and
      2010, in the light of the development of state planning in Brazil and Lula's
      administration. Firstly an historical overview is presented of the key moments
      for national planning, regarding its effects on health care. The governmental
      context is then described with a review of the strategies and instruments in
      health planning over recent years. The methodology involved a bibliographic and
      documental review - including the Multi-year Plans, the National Health Plan, the
      Health Pact and the More Health program - considering their intention, contents
      and development processes. The results indicate that national health planning has
      been condensed in order to enable better direction of the policy. Two key moments
      in federal health planning were identified: between 2003 and 2006 a managerial
      and participative line was followed; between 2007 and 2010, the managerial line
      was kept allied to an effort to tie health policy to the development model.
      Despite the advances, health planning has displayed limitations, such as:
      restrictions in health financing, which has compromised the execution of the
      plans; failure to tackle structural problems in the health care system; and the
      fragile territorial organization.

PMID- 20802871
TI  - [Planning in Brazilian Public Health System: the case of the Health Secretariat
      of State of Bahia].
AB  - The object of this article is the planning process of the Health Secretariat of
      State of Bahia from January 2007 to July 2009. It describes and analyses this
      process, discussing the difficulties and the advances to build the planning
      practice in this institution. It was used documental analyses and systematic
      registers of lived experience by the authors to do it. The process points for an
      approach between theory and practice articulating the Strategic-situational focus
      and the Communicative Action, including the principle of the Social
      Participation. The analyses explain that the process occurs in a pool of dialogic
      movements enlaced by the explicative, normative, strategic and tactic-operative
      moments that finished with the construction of the Health Secretariat of State of
      Bahia. There is a powerful planning revealed in plurality and multiplicity of
      approaches used to build a collective "vision of future" in organizations that
      adopted "plans" like instruments to qualify Government actions.

PMID- 20802872
TI  - [Management of attention to emergency rooms and the federal role].
AB  - Attention to the emergency care has been criticized, and since 2002 the Brazilian
      State has assumed the efforts to standardize the level of attention. It was
      proposed the analysis of documents and acts based on the Structuration Theory
      that considers the mobilization of allocative and authoritarian resources as
      dimensions of structure in interaction, which would justify the legitimacy
      exercised since the establishment of regulations. The National Emergency Plan
      (PNAU) had as guides: the federal funding, regionalization, professional
      education, management by urgency committees, and the expansion of the network. It
      was identified the density of the documental proposals as the facilitator trend
      of the structural resource, innovative due to the regionalization and
      responsibilization proposals presented by the several actors and by the alleged
      centrality of the user. The financing of SUS, despite its persistent state of
      embarrassment, had no coercive action on the technology investment. Under the
      current administration there was a vigorous expansion and structuring of the
      network, which was made by a strong inflow of federal funds. The management by
      committees should be investigated and points out how fragile the management of
      labor is.

PMID- 20802873
TI  - [Health litigation and new challenges in the management of pharmaceutical
      services].
AB  - Health litigation spurs many challenges in the management of pharmaceutical
      services. Performance of health managers and decisionmakers must be adjusted to
      new administrative and legal boundaries. Their actions must also be efficient in
      responding to ongoing lawsuits, as well as in avoiding additional litigation and
      in upholding principles and directives of the Brazilian Health System (SUS). This
      paper proposes to better understand one of the aspects of health litigation,
      namely the growing use of lawsuits demanding medicines, and the relationship
      between this phenomenon and pharmaceutical services management in SUS. Through
      review and analysis of available published research on the subject, from various
      Brazilian states, the main elements of "medicines litigation" are presented and
      examined in light of their interference on the activities of the pharmaceutical
      services cycle. The analysis points to possible mechanisms to be adopted by
      decision-makers in management and in the Judicial System, since the right to
      health can only be effectively established when management and Justice are
      predominantly aware and committed to the safety and the protection of patients
      and users.

PMID- 20802874
TI  - The controversy about a possible relationship between mobile phone use and
      cancer.
AB  - Over the last decade, mobile phone use increased to almost 100% prevalence in
      many countries. Evidence for potential health hazards accumulated in parallel by
      epidemiologic investigations has raised controversies about the appropriate
      interpretation and the degree of bias and confounding responsible for reduced or
      increased risk estimates. Overall, 33 epidemiologic studies were identified in
      the peer-reviewed literature, mostly (25) about brain tumors. Methodologic
      considerations revealed that three important conditions for epidemiologic studies
      to detect an increased risk are not met:no evidence-based exposure metric is
      available; the observed duration of mobile phone use is generally still too low;
      no evidence-based selection of end points among the grossly different types of
      neoplasias is possible because of lack of etiologic hypotheses. The overall
      evidence speaks in favor of an increased risk, but its magnitude cannot be
      assessed at present because of insufficient information on long-term use.

PMID- 20802875
TI  - [Resolutions of the Health Council: instrument of social control or bureaucratic
      document].
AB  - The present study has a documentary character and analyzes the resolutions
      registered in minutes of meetings of a Health Council, as a form to characterize
      the social control in health carried through for this instance. The majority of
      the resolutions were referred to the approval of Programs and Projects, arising
      from the Secretariat of Health, regarding the reform, material and equipment
      acquisition for units of health, the qualification of existing services or the
      creation of new services. The study suggests that the practical one of this
      council seems to be bureaucratic, without any proposal of politics of health for
      the council is visualized. The way the resolutions have being legalized does not
      characterize its guiding not even the visibility of the actions for the
      population in general. In the studied case, it is signaled that the mere regular
      functioning of this council does not guarantee that exist effective social
      control.

PMID- 20802876
TI  - [Municipal Health Council: (re)thinking the gap between the institutional pattern
      and the space of social participation].
AB  - The present essay is involved in the construction of the participation of civil
      society organized in health as a citizenship exercise and the place of Municipal
      Health Council (MHC) in this participation process. The study has as objective to
      analyze the institutional pattern of the MHC of Vicosa, Minas Gerais State,
      approaching the structure and operation dynamics, composition rules and
      competences. It is related to the observational study of traverse stamp, where
      individual interviews with the counselors of health, non participative direct
      observation of meetings of the MHC and documents were used as instrument of
      analysis. A number of 34 members (77,2%) of the respective council were
      interviewed. Among the results, it stands out that 44,2% of the interviewed said
      that the decisions taken in the MHC are not informed to the population and 35,3%
      does not transfer the information of the proposals and discussions taken in the
      MHC for discussion and deliberation for their pairs. For the documental analysis,
      it was verified that the composition of the MHC of Vicosa is not in agreement
      with the foreseen distribution by the federal legislation. The results suggest
      the existence of problems related to the representation, limiting the social
      participation in the councils.

PMID- 20802877
TI  - [Living the process of the municipalization of SUS in Juazeiro do Norte, Ceara
      State].
AB  - The reorganization of the Brazilian health system, the principle of the
      decentralization and municipalization of the health services has demanded a
      deeper knowledge about its reality for people's quality of life. The aim of this
      study is to observe the organizational strategies of the health care in the city
      of Juazeiro do Norte, located in the state of Ceara, through a descriptive field
      research, with a quantitative-qualitative approach, extracting indicators of the
      life conditions of populations and semi-structured interviews held with main
      management demands on the field of SUS. The results proved a reality similar to
      most Brazilian towns, marked by the lack of recourses in the sector, health
      problems of different complexities to resolve, demonstrating a reality with
      certain details, such as: the existence of a big migration population assisted by
      the health system. Thus, it is necessary to analyze SUS with further objectivity,
      by understanding it as a process in permanent construction, taking into account
      the several difficulties to be faced.

PMID- 20802878
TI  - [The participation in health councils and its interface with politics culture].
AB  - The objective of this paper is to analyse the participation of current health
      councils in a city in the north-eastern of Brazil and its relationship with local
      political culture. The following theoretical presumption served as starting
      point: The practices adopted by health councils initiate a new institution that
      involves new social actors - the users - in the public sphere. The process of
      democratisation in the Brazilian society expands this sphere and leads to a
      confrontation of traditional and democratic political cultures. This is a
      qualitative research with the following data collection methods: documentary
      analysis, participant observation and semi-structured interviews. Within the
      evidence emerged, the dominance of traditional political culture resulted as one
      of the conditioning elements of participation practices in the Council, expressed
      in the authoritarianism and cooptation involving municipal managers and
      representatives of civil society. The majority of counsellors recognises the
      fragile power of the Council in terms of deliberative and fiscal issues. Despite
      confirming the frailties of the health councils, it is obvious that their
      importance in the democratisation of the relationship between State and civil
      society in the fight for the implementation of the right to health care.

PMID- 20802879
TI  - [Applicability of the risk scale to the organization of the work process with
      families in a health care unit in the city of Vitoria, Espirito Santo State].
AB  - The objective of this study was to evaluate the applicability of Coelho's scale
      (CS) and to determine its adaptation to the reality observed in the families
      accompanied in the Maria Rangel Passos health care unit (USFMRP) in the city of
      Vitoria, Espirito Santo State. This is a cross-sectional exploratory, descriptive
      study developed in the area of health of Greater Maruipe. First, it was made the
      classification of the families according to CS and the results were presented for
      a discussion group that proposed changes and possible alterations in CS, being
      the new tool denominated as "UFES criterium". In order to verify the
      applicability of that instrument and to accomplish a comparison with the obtained
      results of the classification for CS, thirty families assisted in USFMRP were
      randomly selected and visited, including by the HCA. This new scale allowed to
      identify a larger number of families of minimum risk and to guide the several
      actions accomplished daily in a health care unit, aiming to define priorities and
      to reorient the practices exercised by the professionals heading for the
      consolidation of a more even and integral attendance, centered in the service of
      the real social needs in health of the families assisted in the extent of the
      Family Health Strategy (FHS).

PMID- 20802880
TI  - [The work process in health and the production of care in a Family Health Unit:
      limits to the reception and reflections on the emergency service].
AB  - This study examines the work process of a Family Health Unity (USF) in a small
      municipality, inland the state of Rio de Janeiro. We would like to start with the
      question of what is causing the population registered in a family health program
      to look for the Emergency Service (SE) of a General Hospital. Semi-structured
      individual interviews were conducted with doctors who worked on duty and users in
      the Emergency Service and group interviews with users of a Family Health Unit and
      its staff. In addition, information was also collected by participant
      observation. The theoretical fields of Health Management and Psycho-sociology
      were the grounds of this research. It was concluded that the "modus operandi" of
      the USF, the geographical and organizational accessibility, and the technological
      apparatus of the SE ended up leading the population to seek the General Hospital
      emergency service of the municipality mentioned in this study in acute situations
      of suffering and distress.

PMID- 20802881
TI  - [Health social organizations as a way of public/private management].
AB  - This work has as objective to analyze the implementation process of the Health
      Social Organizations (OSS), in the State of Sao Paulo, focusing the role played
      by factors as administrative and financial autonomy, direction proposed by the
      Management Contract and the use of instruments and innovative management
      practices, as factors that give condition to the gain of efficiency of these OSS
      facing the Direct Administration units (AD). The adopted approach was the
      Comparative Study, which proposes the establishment of possibilities, from the
      confrontation between two units (HOSS and HAD), to identify the elements capable
      of explaining this difference of performance between the two models of
      management. The research points to the positive influence of the administrative
      and financial autonomy, to the direction given to the work processes by goals
      setting in the Management Contract and innovative management technologies with
      the intensive use of the information as base for taking decisions. This result,
      far from indicating the complete conversion of AD to the publicizing by the OSS
      model, points to the possibilities and limits of development of AD, by the
      incorporation of management technologies in the OSS environment.

PMID- 20802882
TI  - [Work regulation in the context of new public versus private relations in
      health].
AB  - This work discusses the management of the work relations in the context of the
      new systems of public vs. private relation in health, having as reference the
      experience of the habilitation of Social Organizations (SO), responsible for the
      administration of a group of hospitals in the state of Sao Paulo. The urgency in
      this kind of management supported on the legal figure of the SO has implications
      in the management of Human Resources in Health (HRH) through the adoption of
      flexibilization mechanisms which include ways of selection, hiring and dismissal,
      payment rules and functional progression similar to the actions adopted by the
      market. The establishment of this sort of administration refers to the new
      paradigm proposed by the managerial administrative reform which suggests the
      exhaustion of the bureaucratic model to promote adjustment of the public
      administration to the transformations originated in the new stage of
      internationalization of the economy and its unfolding in the work world, as well
      as to the new standards of requirements of performance of the public field.
      Aspects related to the management of HHR are approached in the two ruling
      modalities in the Secretaria de Estado da Saude de Sao Paulo: Direct
      Administration Hospitals (DAH) and units organized under the SO model (SOH).

PMID- 20802883
TI  - [Issues regarding the effects on health of income inequality: contextual
      mechanisms].
AB  - Brazil is one of the most unequal countries in income distribution. The influence
      of this factor on people's health is controversial. This article reviews the
      contextual effects and possible pathways linking income inequality to health.
      Contextual effect studies need well-developed multilevel theories, identifying
      the roles of variables in the explaining model, especially the role of individual
      level variables and the level of aggregation of contextual variables. Four
      explanations for the relationship between income inequality and health were
      identified: (1) statistical artifact; (2) social comparison; (3) underinvestment
      in social police; (4) social capital. The relative contribution of each of these
      mechanisms has not been well evaluated yet. We concluded that part of the
      heterogeneity found in the studies results may be explained by different
      pathways. Alternatively, income inequality may be a proxy for social
      stratification and less investment in public policies, but the Gini coefficient
      may be an unsuitable marker for such constructs in certain circumstances. More
      powerful designs to ascertain cause relationship should be applied. One
      possibility is to study the effect of intervention policies aimed at income
      redistribution.

PMID- 20802884
TI  - Evaluation methods in health promotion programmes: the description of a
      triangulation in Brazil.
AB  - Evaluation is a key word in any health promotion programme. However, it is a
      challenge to choose the most appropriate method of evaluation. The purpose of
      this paper was to describe a triangulated methodology developed to evaluate a
      health promotion intervention based on intergenerational activities and to
      describe the theoretical framework, which guided the study. From February to
      December 2002 a triangulation involving a community controlled trial, focus
      groups technique and observation process was developed in Ceilandia, Federal
      District of Brazil. Samples of 253 students aged 12 to 18 years old from a
      secondary school and 266 elders aged 60 and over from the local area were
      randomly allocated to control and experimental groups. Over four months, 111
      students and 32 elders had weekly meetings at school to share their life
      histories. Before and after the intervention, a questionnaire was administered to
      control and experimental groups including the outcome variables. Although the
      study had some limitations, it was valuable in showing for the first time that
      this method can be used in interventions of this kind and also to show the
      importance of developing a theoretical framework to understand possible mechanism
      of interactions in intergenerational interventions.

PMID- 20802885
TI  - [Self-medication and health academic staff].
AB  - As self-medication is a worldwide problem of public health, this article had as
      objective to evaluate the behavior of the future health professionals with regard
      to the drug utilization, particularly, to the self-medication practice. 223
      academic students from a public university in Recife City were interviewed,
      selected by proportional share in each course. A questionnaire on the drug
      utilization was applied, 15 days before the interview. From the 223 students,
      65.5% reported drug use in the last 15 days. 42.3% used drugs through the
      physician's prescription and 57.7% through the self-medication. The most used
      drugs were the analgesics (24.0%) and vitamins (18.9%) and the main reason was
      pain (30.5%). The drug utilization among academic students in Recife City is high
      but it is inside the parameter according to others analysis. However we have
      expected a low and more rationalized utilization.

PMID- 20802886
TI  - [Health education: a historical reflection of its practices].
AB  - This text aims to contextualize the transformations occurred in the practice of
      health education since the political scenario in the end of 19th century, when
      the first extended initiatives of the Brazilian State in the health field were
      organized, until the creation of the Brazilian Unified Health System.

PMID- 20802887
TI  - [Health sciences education: dialogues in public health and the education for the
      citizenship].
AB  - In the last decades there have been discussions concerning the educational
      process of health professionals in Brazil. The discussed subjects are based on
      the verification of precarious aspects concerning a kind of formation that should
      be focused on attending the demands of the population, on the principles of SUS
      and an extended understanding of healthcare. We intended to think about
      alternatives in relation to the graduation in health sciences and in analyzing
      the way education in health is registered in the context of higher education.

PMID- 20802888
TI  - [Speech-language pathology formation in the city of Salvador and the
      consolidation of SUS].
AB  - The Human Resources in Health (HRH) academic field is recognized as a critical
      area, which is part of the reorientation process in the health sector. The
      elaboration of the Unified Health System (SUS) represents challenges to the
      academic field process, especially regarding new careers such as speech-language
      pathology. This is related with the lack of awareness regarding collective health
      and the past history that strengthened the public health policies in Brazil. Yet,
      the powerful influence of the service model to the spontaneous demand and
      reabilitation therapy plays another key role in the aspect. The aim was to
      analyze the academic field of the speech-language pathology profile in the city
      of Salvador, Bahia State. Documental analysis and coordinator interviews were
      used to investigate how the public area is characterized in 3 modules. It was
      noticed little adhesion of the upper level institutions to the legislation of the
      field; lack of contact between graduating students and collective health, and a
      teaching-service disconnection. The graduation of the speech therapist was shown
      incipient regarding SUS's consolidation. Identifying challenges and opportunities
      of changes in HRH formation in upper level institutions may lead to better levels
      of aid to the population, quality of education and expansion of theoretical and
      practical models of knowledge.

PMID- 20802889
TI  - [Contributions from the critical leisure field to the health promotion].
AB  - The studies about leisure for health promotion still tend to choose the active
      body occupation in the free-time (leisure activities), revealing the influence of
      the functionalist way of thinking, which trying to reduce the links between
      society and health-disease process, undoubtedly do not keep with the purpose of
      population health promotion. Focusing on this idea, and keeping in mind the
      premise that in the Brazilian physical training there are different opinions
      since the earliest 80s which try to achieve the purpose to avoid the ideas of the
      functionalist way of thinking. However, those opinions are almost unknown both in
      the Brazilian public health system and the collective health system, once the
      bibliography revision about leisure activities development was made in the
      country, looking for ideas taken in common knowledge for health promotion
      presuppositions, this report has the aim to show critical and alternatives
      concepts of leisure in the way it is linked to healthy as a real social change,
      using a political-pedagogical proposal called lazerania. In general, this is an
      emancipatory concept of leisure, which comes from the sport phenomenon as a
      problem and provides the feeling, thinking and behavior of the population, trying
      to build a society based on solidarity and consumer participation.

PMID- 20802890
TI  - [The federal politics of basic sanitation and the initiatives of participation,
      mobilization, social control, health and environmental education].
AB  - The purpose of this article is to accomplish a critical analysis of two
      governmental important programs in health and environmental education - Health
      Education and Social Mobilization Program (PESMS) and Environmental Education and
      Sanitation Social Mobilization Program (PEAMSS), aiming at stimulate
      participative educational actions and social mobilization in sanitation projects.
      The methodology was based on reading and analysis of documents and observation in
      Workshops, Meetings, Seminars, Conventions, Congresses and Interviews. The
      authors describe the process of Program creation - PESMS and PEAMSS. They
      promoted a reflection and thought about Participation, Mobilization, Social
      Control, Health Education and Environmental Education. They also made
      considerations about the difficulties, facilities, advances and challenges in the
      implantation and implementation of PESMS and PEAMSS in the fundament for the
      realization of the public services of basic sanitation. They conclude that the
      creation of conditions by means of initiatives of Participation, Mobilization,
      Social Control, Health Education and Environmental Education become necessary for
      the development of Federal Policies of Basic Sanitation.

PMID- 20802891
TI  - [Evaluation of tutors and facilitators on the formation process of facilitators
      on Permanent Health Education of Londrina, Parana].
AB  - The Ministry of Health has instituted the Permanent Health Education (PHE) with
      the purpose to change both the practices and the education of health
      professionals. As a strengthening strategy of this policy, the formation of PHE
      tutors and facilitators has begun in the whole country. This project aims to
      analyze this individuals' perception on the PHE facilitator course in Londrina,
      PR. It is a qualitative study, carried out with PHE tutors and facilitators from
      December 2006 to January 2007. Data were collected through semi-structured
      interviews and submitted to the discourse analysis proposed by Martins and
      Bicudo. By analyzing two categories the study revealed: Contributions from the
      permanent health education course and Critics on the facilitators' formation
      process. The results showed that despite some limitations such as the course
      period, selection of facilitators and difficulties with the course methodology,
      the education of facilitators has brought contributions to the systematical
      knowledge on PHE and the opportunity to reflect upon the practices in health.

PMID- 20802892
TI  - [Reasons for medical follow-up dropout among patients with arterial hypertension:
      the patient's perspective].
AB  - Arterial hypertension is a relevant public health problem as it is a risk factor
      for cardiovascular diseases, the major cause of mortality in Brazil. Low
      compliance and treatment dropout are among the main obstacles to individual
      control strategies. This study aimed at assessing the reasons for failure in
      medical appointment follow-up among a cohort of patients under treatment for four
      years in a primary care service. Thus, semi-structured interviews were conducted
      with 50 individuals who had dropped out of medical appointments. Statements were
      assessed by using thematic content analysis. The reported reasons for dropping
      out were most frequently related with the healthcare service itself - its
      organization and structure, and doctor-patient relationship - or treatment at
      another healthcare service. The reasons related with the patients themselves,
      such as absence of symptoms, improvement and/or normalization of arterial
      hypertension, as well as alcohol consumption contributed to the discontinuation
      of the treatment. To study the reasons for treatment dropout through the
      patients' eyes showed the abundance and diversity of problems involved.

PMID- 20802893
TI  - [Necessities of professionals of the family health teams from the "4a
      Coordenadoria Regional de Saude do Estado do Rio Grande do Sul" for training and
      improvement].
AB  - This study had the aim to verify the necessities of training and improvement of
      the 4th Regional Coordination in Health of Rio Grande do Sul State family health
      teams. The data collection was carried out through the application of
      questionnaires with objective questions, composed by two parts: field and
      competence nucleus. For data analyses, Normality, Chi-Square and G tests were
      used as statistical procedures for Easy and Difficult attributions indicated by
      the professionals. Professionals have shown less difficulty with generic
      attributions, related with basic methods and techniques of each health area.
      However, they have revealed a lot of difficulties with attributions relating to
      the search of new partners in health inside communities, stimulation of the
      people participation in the discussion of health rights, and completion of the
      SIA/SIAB forms, and others. Even after 12 years of the foundation of the Family
      Health Program (PSF), several difficulties are still observed concerning the way
      to work with this new health strategy in Brazil. Proposals are made for the
      complete understanding and improvement of the PSF strategy.

PMID- 20802894
TI  - [Home care: searching for individual and family's autonomy in the public scope].
AB  - The objective of this essay is to reflect on the possibility of searching for
      individual and family's autonomy in public health services through health
      professionals, mainly nurses in the development of home care. Some aspects
      related to the organization and health professionals' education must be
      considered in order to perform home care in health systems, mainly in the public
      service scope. Effective home care must watch individuals and their families in
      their context, visualizing and considering their social environment, their
      insertions, their homes, their habits and relationships, and anything or any
      situation that are part of their existence in the world. Autonomy - for
      individuals as well as their families to be able to carry out home care during an
      illness - is the possibility to deliver care supported by the health system, with
      professionals teaching, guiding and giving follow up, mainly a sensitive and
      technically-scientifically competent nurse to set up caring goals attending
      health reality - lived disease.

PMID- 20802895
TI  - [Theoretical and conceptual contribution to evaluative research in health
      surveillance context].
AB  - Initially this article revises some of the conceptual and operational elements on
      evaluative research by gathering knowledge and action fields on public health
      practices. Such concepts are taken according to a wider conception of quality.
      Then, the article intends to arrange a theoretical model design considering the
      proposition for implementation of health surveillance actionsAn image-objective
      definition of organization and integration of health polices and practices based
      on hierarchic and local logic also take place. Finally, becomings and challenges
      around the theory in the health evaluation field turn to be the aim of our
      reflection in order to enable the production of knowledge and approaches to
      construct logic models which reveals the complexity of interventionist objects as
      well as its transforming nature of social practices.

PMID- 20802896
TI  - [Health transmission and obtaining of information].
AB  - By identifying the resulting benefits of the application of a information program
      (constituted by pamphlets accompanied by verbal information), either in the
      change of the nurses behaviour to the transmission of information, or in the
      obtaining of the same by the patients, it was possible to develop a systematized
      knowledge that allowed to clarify the nurses role in the hospital internment, and
      that the specified in the letter of the rights and duties of the patient could be
      respected. The aims of this study are to identify how the application of an
      information program produces changes in the nurses' behaviour in transmitting the
      information, and to verify the effectiveness of the introduction of a information
      program regarding the information obtaining on the part of the patients. It was
      an experimental study and the populations that were in the base of this study
      were composed by patients interned in medicine services and surgery services and
      for nurses that exercise its profession in medicine services and in surgery
      services. We conclude that the share attitude of information is higher in nurses
      of the group submitted to an information program comparing to the ones who were
      not. Similarly, patients of the group submitted to a information program obtained
      more information.

PMID- 20802898
TI  - Factors associated with physical activity in adults in Brasilia, Central-West
      Brazil.
AB  - OBJECTIVE: To describe physical activity practice in adults and to identify
      associated factors. METHODS: A cross-sectional study was performed with cluster
      sampling from the four areas of the city of Brasilia, Central-West Brazil, in
      2006-2007. A sample comprised of 469 adults was obtained from 250 randomly
      selected households. Sociodemographic data, weight and height were obtained
      during a household interview. The short version of the International Physical
      Activity Questionnaire (IPAQ) was used to measure physical activity. A
      multivariate linear regression analysis was made to assess the effect of sex,
      body mass index (BMI), socioeconomic classification and marital status on
      physical activity scores. RESULTS: The majority of the sample was comprised of
      women (57%). The percentage of individuals who achieved 150 minutes of weekly
      physical activity practice was 52% (95% CI: 47; 56), while that of inactive
      individuals was 21.5% (95% CI: 17.8; 25.3). An inverse association between
      physical activity and BMI was only found in men. Types of physical activity
      reported differed between sexes: walking and doing household chores among women;
      cycling, running, swimming and weight-lifting among men. There was a strong
      interaction between male sex and BMI in terms of the association with physical
      activity scores: the higher the BMI, the lower the physical activity score.
      CONCLUSIONS: The portion of inactive individuals in Brasilia can be considered
      low, when compared to estimates from other Brazilian cities. Differences in BMI
      and physical activity score found between sexes are associated with the type of
      physical activity practiced.

PMID- 20802899
TI  - Social costs of two cataract surgical techniques in Brazil.
AB  - OBJECTIVE: To compare postoperative social costs of two cataract surgical
      techniques, phacoemulsification (PHACO) and extracapsular extraction (ECCE).
      METHODS: Prospective randomized intervention study including 205 patients, of
      which 101 underwent PHACO and 104 ECCE in the public service, in the city of Sao
      Paulo, Southeastern Brazil, in 2002. The socioeconomic impact of these surgical
      procedures was assessed based on postoperative costs for patients, employers and
      social security. Comparisons between the two groups studied were performed using
      the chi-square test or Mann-Whitney test, when appropriate. A 5% significance
      level was set. RESULTS: Hospital and eyeglasses costs for PHACO were lower than
      for ECCE patients, with a mean difference of US$ 16.74. Costs to employers
      related to medical leave for the first 15 days of absence and costs of caregivers
      in the form of absence from work to attend postoperative follow-up visits were on
      average US$ 0.18 lower in PHACO compared to ECCE group. The estimated Social
      Security expenditure per patient undergoing surgery was US$ 6.57 and US$ 51.15 in
      PHACO and ECCE groups, respectively. CONCLUSIONS: The average saving with PHACO
      compared to ECCE technique was US$ 61.50 for employers, patients, caregivers and
      Social Security.

PMID- 20802900
TI  - Prevalence of hospitalization and associated factors in Pelotas, Southern Brazil.
AB  - OBJECTIVE: To estimate the prevalence of hospitalizations and to identify
      characteristics associated with hospital admission. METHODS: We carried out a
      population-based cross-sectional study of subjects of both sexes, aged 20-69
      years, and who lived in the urban area of Pelotas, Southern Brazil, between 1999
      and 2000. Subjects were interviewed using a standardized, pre-coded
      questionnaire. Analysis was stratified by sex and confounder control was carried
      out using Poisson regression. Variables analyzed included socioeconomic and
      demographic characteristics, lifestyle, morbidities, and medical appointments in
      the last year. RESULTS: Of the 1,916 subjects interviewed, 146 (7.6%; 95%CI:
      6.4;8.8) had been hospitalized in the year preceding the interview. Among men,
      characteristics associated with hospitalization included age above 50 years,
      schooling between five and seven years, history of smoking, minor psychiatric
      disorders, and medical appointments in the last year. For women, hospitalization
      was more frequent among subjects aged 60-69 years, with five to seven years of
      schooling, and who had had medical appointments within the last year. Women who
      consumed under 30 g/day of alcohol were less likely to have been hospitalized.
      Prevalence of hospitalization for primary care-sensitive causes was 13.0% (95%CI:
      7.6;18.5). CONCLUSIONS: Prevalence of hospitalization is similar in men and
      women. Schooling, but not income, was found to be associated with
      hospitalization.

PMID- 20802902
TI  - Change the Qualis criteria!

PMID- 20802903
TI  - The article of the future.
AB  - Technological advances and the Internet have contributed to the increased
      disclosure and updating of knowledge and science. Scientific papers are
      considered the best form of disclosure of information and have been undergoing
      many changes, not on their way of development, but on the structure of
      publication. The Future paper, a name for this new structure, uses hypermediatic
      resources, allowing a quick, easy and organized access to these items online. The
      exchange of information, comments and criticisms can be performed in real time,
      providing agility in science disclosure. The trend for the future of documents,
      both from professionals or enterprises, is the "cloud computing", in which all
      documents will be developed and updated with the use of various equipments:
      computer, palm, netbook, ipad, without need to have the software installed on
      your computer, requiring only an Internet connection.

PMID- 20802904
TI  - Cardiogenic shock due to cytomegalovirus myocarditis: successful clinical
      treatment.
AB  - OBJECTIVE: Cytomegalovirus (CMV) systemic disease and myocarditis in healthy
      persons is infrequently reported in the literature, although in increasing
      numbers in recent years. The importance of the recognition of the syndrome that
      usually has an initial picture of a mononucleosis like infection in an otherwise
      healthy person, is the available therapeutic agent, ganciclovir, that can cure
      the infectious disease. METHODS: We analyzed the clinical result of pulsotherapy
      with steroids in a patient with CMV myocarditis after 7 days of etiological
      treatment, with ganciclovir, intravenous vasodilators, and the conventional
      treatment for congestive heart failure. RESULTS: The clinical condition of the
      patient improved accordingly to the better function of the left ventricle, and
      the ganciclovir was kept for 21 days, most of it in an out patient basis. The
      patient was dismissed from the hospital, with normal myocardial function.
      CONCLUSION: Potentially curable forms of myocarditis, like M pneumoniae and CMV,
      for example, can have an initial disproportionate aggression to the myocardium,
      by the acute inflammatory reaction, that can by itself make worse the damage to
      the LV function. In our opinion, the blockade of this process by pulsotherapy
      with steroids can help in the treatment of these patients. We understand that the
      different scenario of immunosuppressive treatments for the possible auto immunity
      of the more chronic forms of the presumably post viral cardiomyopathy has been in
      dispute in the literature, and has stolen the focus from the truly acute cases.

PMID- 20802905
TI  - Risk score elaboration for mediastinitis after coronary artery bypass grafting.
AB  - INTRODUCTION: The mediastinitis is a serious postoperative complication of
      cardiac surgery, with an incidence of 0.4 to 5% and mortality between 14 and 47%.
      Several models were proposed to assess risk of mediastinitis after cardiac
      surgery. However, most of these models do not evaluate the postoperative
      morbidity. OBJECTIVE: This study aims to develop a score risk model to predict
      the risk of mediastinitis for patients undergoing coronary artery bypass
      grafting. METHODS: The study sample included data from 2,809 adult patients
      undergoing coronary artery bypass grafting between January 1996 and December 2007
      at Hospital Sao Lucas -PUCRS. Logistic regression was used to examine the
      relationship between risk factors and the development of mediastinitis. Data from
      1,889 patients were used to develop the model and its performance was evaluated
      in the remaining data (n=920). The definitive model was created with the data
      analysis of 2,809 patients. RESULTS: The rate of mediastinitis was 3.3%, with
      mortality of 26.6%. In the multivariate analysis, five variables remained
      independent predictors of the outcome: chronic obstructive pulmonary disease,
      obesity, surgical reintervention, blood transfusion and stable angina class IV or
      unstable. The area under the ROC curve was 0.72 (95% CI, 0.67-0.78) and P = 0.61.
      CONCLUSION: The risk score was constructed for use in daily practice to calculate
      the rate of mediastinitis after coronary artery bypass grafting. The score
      includes routinely collected variables and is simple to use.

PMID- 20802906
TI  - Correlation between right atrial venous blood gasometry and cardiac index in
      cardiac surgery postoperative period.
AB  - OBJECTIVE: To determine, even during postoperative period, the confiability of
      the cardiac index correlate with the data data given by a central atrial venous
      blood gasometry in patients who underwent cardiac surgery. METHODS: From the
      sample of arterial and venous blood of right atrium gathered in postoperative of
      cardiac surgery, it was determinated the hemoglobin concentration and the
      gasometric study through what was observed of the venous oxygen saturation (SvO2)
      and the partial pressure of oxygen from venous blood gathered in right atrium
      (PvO2), add to the calculation of artery-venous difference of the oxygen content-
      radial artery / right atrium (C( a-v )O2). Afterwards, these parameters were
      compared with the cardiac index determined by thermodilution. RESULTS: There was
      good correlation between SvO2, C(av)O2 of the venous right atrial blood and
      cardiac index measured by thermodilution method, with sensibility and specificity
      good and high positive predict value and negative predict value. The PvO2
      demonstrated poor sensibility in the estimative of low output. CONCLUSION: In
      cardiac surgery postoperative, the SvO2 and the C(a-v)O2 were safe parameters
      correlated with low cardiac output. The PvO2 demonstrated poor sensibility in the
      estimative of low output in postoperative cardiac surgery.

PMID- 20802907
TI  - Complications that increase the time of Hospitalization at ICU of patients
      submitted to cardiac surgery.
AB  - OBJECTIVE: To show the complications that increase the permanence at intensive
      care unit (ICU) of the patients submitted to cardiac surgery. METHODS: Eighty
      five handbooks of patients submitted to cardiac surgery had been analyzed,
      retrospectively, from March to May 2009 at Santa Casa de Misericordia de Juiz de
      Fora (MG)--Brazil--and 14 (16.47%) patients had been studied. They remained more
      than 5 days at ICU. In 85 patients occurred three deaths: two patients operated
      in urgency character and this increases the morbidity; one patient who remained
      in mechanical ventilation (MV) by 21 days. RESULTS: Complications that had
      increased the time of hospitalization at ICU had been respiratory and metabolic
      in accordance with literature. CONCLUSION: Complications that increase the time
      of permanence at ICU are those related to respiratory function, chronic
      obstructive pulmonary disease, tabagism, pulmonary congestion, time of permanence
      under MV, diabetes, infections, renal insufficiency, stroke and hemodynamic
      instability.

PMID- 20802908
TI  - [Quality of service provided to heart surgery patients of the Unified Health
      System-SUS].
AB  - OBJECTIVE: To evaluate the service quality provided to heart surgery patients
      during their hospital stay, identifying the patient's expectations and
      perceptions. To associate service quality with: gender, age and the use of
      extracorporeal circulation. METHODS: We studied 82 elective heart surgery
      patients (52.4% females and 47.6% males), operated by midsternal thoracotomy,
      age: 31 to 83 years (60.4 +/- 13.2 years); period: March to September 2006.
      Service quality was evaluated in two instances: the expectations at pre-operative
      and the perceptions of the service received on the 6th post-operative; through
      the application of the modified SERVQUAL scale (SERVQUAL-Card). The result was
      obtained by the difference of the sum of the scores on perception minus those of
      the expectations, and through statistical analysis. RESULTS: The SERVQUAL-Card
      scale was statistically validated, showing adequate level of internal
      consistency. We found a higher frequency of myocardial revascularization 55
      (67.0%); first heart surgery 72 (87.8%) and the use of ECC 69 (84.1%). We noticed
      high mean values for expectations and perceptions with significant results
      (P<0.05). We observed a significant relationship between the quality of service
      with: gender, in empathy (P= 0.04) and age, in reliability (P = 0.02). There was
      no significant association between ECC and quality of service. CONCLUSION:
      Service quality was satisfactory. The patient demonstrated a high expectation to
      hospital medical service. Women present a higher perception of quality in empathy
      and younger people in reliability. The use of ECC is not related to service
      quality in this sample. The data obtained in this study suggest that the quality
      of this health service can be monitored through the periodical application of the
      SERVQUAL scale.

PMID- 20802909
TI  - Risk index proposal to predict atrial fibrillation after cardiac surgery.
AB  - OBJECTIVE: Atrial fibrillation (AF) is a common complication following cardiac
      surgery and is associated with an increased patient morbidity and mortality. The
      objective of this study was to develop a risk index proposal to predict AF after
      cardiac surgery. METHODS: A prospective observational study in that 452 patients
      were selected to assess the incidence and risk factors associated with
      postoperative AF. Only patients following cardiac surgery were selected.
      Continuous cardiac monitor and daily electrocardiogram were assessed. The most
      associated in a multivariable logistic model were selected for the risk index.
      RESULTS: The average incidence of AF was 22.1%. The most associated factors with
      AF were: patients older than 75 years of age, mitral valve disease, no use of a
      beta blocker, withdrawal of a beta-blocker and a positive fluid balance. The
      absence risk factor determined 4.6% chance to postoperative AF, and for one, two
      and three or more risk factors, the chance was 16.6%, 25.9% and 46.3%,
      respectively. CONCLUSION: In a multivariable logistic model was possible to
      develop a risk index proposal to predict postoperative AF with a major risk of
      46.3% in the presence of three or more risk factors.

PMID- 20802910
TI  - Perioperative variables of ventilatory function and physical capacity in heart
      transplant patients.
AB  - INTRODUCTION: Heart transplantation is currently the only widely accepted
      surgical alternative to treat patients with severe heart failure (HF) drug
      therapy cannot maintain optimal quality of life appropriate. OBJECTIVE: To
      describe and to compare the values between pre-and postoperative physical
      capacity and pulmonary patients who underwent heart transplantation. METHODS: A
      retrospective cohort composed of patients undergoing heart transplantation
      between January 2001 to March 2005 in IC-FUC/RS. RESULTS: Were included in the 21
      individuals. We observed decreased levels of volume and lung capacity (FEV1 and
      FVC) in the first days after surgery compared to preoperatively (P <0.001) and
      recovery of these values in the 14th postoperative day (P <0.001). The values of
      muscle strength showed similar trends in reducing post-operative period compared
      to preoperative (P <0.001) and recovered on the 14th postoperative day (P
      <0.001). A useful functional capacity, measured by testing 6-minute walk test
      (T6') showed improvement in the 14th postoperative day in relation to pre
      operatively (P <0.001). CONCLUSION: Changes in ventilatory function of subjects
      undergoing cardiac transplantation are predictable, but these recover respiratory
      muscle strength and lung capacity within two weeks, and improve functional
      capacity useful in relation to pre-operative, the transplantation, when
      indicated, associated with good functional rehabilitation is very god treatment
      strategy.

PMID- 20802911
TI  - Comparative study of traditional long incision vein harvesting and multiple
      incisions with small skin bridges in patients with coronary artery bypass
      grafting at King Abdullah University Hospital--Jordan.
AB  - OBJECTIVE: Saphenous vein harvesting can be associated with wound complications,
      incision pain, infection, and poor cosmetic outcome. The objective of our study
      is to determine the difference in wound complication and infection rates between
      two saphenous vein harvesting techniques, long incision versus multiple short
      interrupted incisions (tunneling) for coronary artery bypass grafting at the King
      Abdullah University Hospital--Jordan. METHODS: Retrospectively we analyzed data
      from 1,050 consecutive elective coronary artery bypass procedures performed from
      May 5, 2003, to December 31, 2007, in our institution. Saphenectomy using
      traditional Long incision vein harvesting (Group 1) performed in six hundred and
      fifty patients (n=650), while saphenectomy using multiple incisions with small
      skin bridges--tunneling (Group 2) performed in four hundred patients (n=400).
      Saphenectomy performed by the cardiac surgery assistant or main cardiac surgeon.
      Inflammation, dehiscence, cellulites, lymphangitis, drainage, necrosis, or
      abscess necessitating dressing, antibiotics or debridement before complete
      healing without eschar were defined as wound complications. There was no
      statistical difference in preoperative risk factors in both groups. Test results
      were considered significant when P<0.05. RESULTS: Leg wound complications
      observed more in traditional long incision vein harvesting technique (P=0.0005).
      Female gender, obesity, diabetes are associated with an increased incidence of
      wound problems (P<0.05). CONCLUSIONS: Saphenous vein harvest using saphenous vein
      tunneling was associated with fewer wound complications than the traditional
      longitudinal method.

PMID- 20802912
TI  - Endovascular techniques and procedures, methods for removal of intravascular
      foreign bodies.
AB  - INTRODUCTION: The incidence of intravascular embolization of venous catheters
      reported in the world medical literature corresponds to 1% of all the described
      complications. However, its mortality rate may vary between 24 to 60%. Catheter
      malfunction is the most likely signal of embolization, since patients are usually
      asymptomatic. OBJECTIVE: To report the method of removing intravascular foreign
      bodies, catheters with the use of various endovascular techniques and procedures.
      METHODS: This is a two-year retrospective study of 12 patients: seven women and
      five men. The average age was 29 years (ranging from two months to 65 years).
      RESULTS: Technical performance was 100% successful. Ten port-a-caths, one intra
      cath and one PICC were extracted. The most common sites for the lodging of one of
      the ends of the intravascular foreign bodies were the right atrium (41.6%) and
      the right ventricle (33.3%). In 100% of the cases, only one venous access was
      used for extraction of foreign bodies, and in 91.6% of the cases (11 catheters)
      the femoral access was used. The loop-snare was used in 10 cases (83.3%). The
      most common cause of intravascular foreign body insertion was a catheter
      fracture, which occurred in 66.6% of the cases (eight cases). One major
      complication, the atrial fibrillation, occurred (8.3%), which was related to the
      intravascular foreign body extraction. The mortality rate in 30 days was zero.
      CONCLUSION: Percutaneous retrieval of intravascular foreign bodies is considered
      gold standard treatment because it is a minimally invasive, relatively simple,
      safe procedure, with low complication rates compared to conventional surgical
      treatment.

PMID- 20802913
TI  - Application of the EuroSCORE in coronary artery bypass surgery in public
      hospitals in Rio de Janeiro, Brazil.
AB  - BACKGROUND: Risk stratification models are used to assess the risk of death in
      surgery. OBJECTIVE: To conduct a critical analysis of the EuroSCORE logistic
      model (ES) application in 2,692 patients undergoing Coronary Artery Bypass
      Grafting (CABG) in four public hospitals in the Rio de Janeiro Municipality, from
      1999 through to December 2003. METHODS: Random samples of 150 medical records for
      surviving and deceased patients were selected at four public hospitals in the
      City of Rio de Janeiro. The ES was applied, using the logistical model. The
      observed lethality rate and that forecast by the model were compared. The
      measurement of the discriminatory power was estimated by the area under the ROC
      curve. RESULTS: 546 of the 600 selected medical records were located. A
      significant difference was noted between the prevalence rates for the risk
      factors in the Brazilian and European populations. The forecast lethality rate
      was 3.62% (CI-95%: 3.47-3.78) while the estimated observed rate was 12.22% (CI
      95%- 10.99-13.46). In all risk ranges, the predicted lethality rate is under
      estimated, with notable differences between the predicted and observed rates. The
      area under the ROC curve was estimated at 0.62. CONCLUSION: The differences in
      the prevalence rates for the risk factors constituting the ES, associated with
      its low power of discrimination, hamper any recommendation of the use of this
      model in Brazil, without the necessary adjustments.

PMID- 20802914
TI  - Comparison of patency between radial artery and saphenous vein in a coronary
      artery bypass grafting post operative with return of the symptoms.
AB  - OBJECTIVE: To compare the radial artery and saphenous vein's patency in patients
      with recurrence of symptoms in a coronary artery bypass grafting (CABG). METHODS:
      Retrospective study. From January 1998 to December 2005, 469 CABGs were performed
      using the radial artery as a graft, in Vera Cruz Hospital in Belo Horizonte/ MG.
      Among the patients who underwent those surgeries, 94 presented ischemic changes
      in early or late postoperative period, which led them to be re-evaluated by
      coronary angiography. The grafts were divided in three groups: internal thoracic
      artery (ITA), radial artery (RA) and saphenous vein (SV), and they were
      stratified according to the severity of injury: uninjured or patent (< 70%),
      severe obstruction (70 to 99%) and occlusion. RESULTS: For the 94 patients in the
      study, 86 grafts of ITA, 94 of RA and 111 of SV were used. For the 86 ITA grafts,
      73 (84.88%) were found patent. For the 94 RA grafts, 55 (58.51%) were found
      patent, and for the 111 SV grafts, 73 (65.76%) were uninjured. A statistically
      significant difference (P= 0.001) was found between RA and SV grafts, with a
      higher patency found for VS graft. For the RA grafts, women presented a worse
      result concerning the RA patency (65.7% and 40.7%), with P = 0.006. Concerning
      coronary revascularization, a statistically significant difference was found only
      for the grafts used for the right coronary, with a better result for the SV (P =
      0.036). CONCLUSION: Radial artery (RA) presented worse results when compared to
      Saphenous vein (SV) as a second graft in a CABG, especially in women who were
      anastomosed in the right coronary artery.

PMID- 20802915
TI  - Changes in functional capacity of patients two years after coronary artery bypass
      grafting surgery.
AB  - OBJECTIVE: To check changes in the functional capacity of patients undergoing
      coronary artery bypass grafting (CABG) by testing six-minute walk test (6MWT)
      following two years. METHODS: A prospective cohort study where 215 patients were
      enrolled who underwent CABG, 13 did not meet the criteria for inclusion. 202
      patients were evaluated preoperatively, 13 died during hospitalization and 6 in
      the follow up of two years. Four patients were considered lost follow up. This
      study followed 179 patients for two years classified into active and sedentary,
      according to physical activity in leisure time and to the 6MWT preoperatively and
      2 years later. RESULTS: One hundred and twenty patients were evaluated in the day
      before CABGS, being 67% male with an average age of 63 (+/- 9.75) years. Before
      surgery and 2 years later, 52 were active and the 6MWT distances performed had
      been 359m (+/- 164.47) and 439m (+/- 171.34), respectively; P= 0.016. Forty five
      patients were classified as sedentary before and 2 years after surgery. The 6MWT
      distances walked before and after surgery had been 255m (+/- 172.15) and 376m (+/
      210.92), respectively; P < 0.001. Eighty two patients transited between these
      two groups, 71 passed from sedentary to active and had walked before and after
      surgery 289m (+/- 157.15) and 380m (+/- 125.44), respectively; P= 0.001. The 11
      patients who were active and passed to the sedentary group walked 221m (+/-
      191.91) and 384m (+/- 63.73), respectively; P= 0.007. CONCLUSION: The functional
      capacity of the patients submitted to CABGS had a significant improvement in a
      medium period of follow-up.

PMID- 20802916
TI  - Outcomes after coronary artery bypass in aged patients.
AB  - OBJECTIVES: Analyze the octogenarians patients submitted to the surgical
      myocardium revascularization (CABG) with and without extracorporeal comparing the
      clinical outcomes and its survival curves. METHODS: Observational study of the
      cohort type involving 396 octogenarians submitted to the CABG between 01/01/ 2000
      and 01/01/2007. Elaboration of an itinerary for collection of data of the
      handbooks containing 36 variables. Comparison between groups using t test for
      independent samples, chisquare and survival curves using Kaplan Meier. RESULTS:
      We analyzed 290 patients that possessed appropriate information. The first group
      G1, of the patients operated without extracorporeal, was constituted of 111
      patients and the second group G2, of the operated ones with extracorporeal was
      constituted of 179 patients. The univariate analyzes had presented statistics
      significance for the variables: cardiac insufficiency functional class
      preoperative (P=0.000), tobacco smoking (P=0.050), number of performed grafts
      (P=0.050), graft type (P=0,000), associates procedures (P=0.000), preoperative
      use of intra-aortic balloon (P=0.000), hospital mortality (P=0.000) and type of
      death (P=0.020). In the postoperative outcomes stroke (P=0,036), re-internment
      for angina (P=0,038). The analyze of the survival curves presented statistic
      difference (P=0,009). CONCLUSIONS: Hospital mortality and stroke were bigger in
      the G2 In the long time the patients of the G1 had respectively presented greater
      number of re-internments for angina and the late mortality was larger in G2 for
      the largest prevalence of cardiac deaths.

PMID- 20802917
TI  - Pulmonary complications in pediatric cardiac surgery at a university hospital.
AB  - OBJECTIVE: To identify the prevalence of pulmonary complications in children
      undergone cardiac surgery, as well as demographic and clinical characteristics of
      this population. METHODS: The sample comprised 37 children of both genders,
      underwent cardiac surgery at the Hospital Universitario Presidente Dutra, Sao
      Luis (MA) during the year of 2007. There were not included patients who had lung
      disease in pre-operative period, patients with neurological disorders, intra
      operative death besides lack of data in medical records. The data were obtained
      from general medical and nursing staff of their medical records. RESULTS: The
      population of the study was predominantly composed by female children, from the
      countryside and at school age. Pathologies considered low risk were the majority,
      especially the patent ductus arteriosus, interventricular communication and
      interatrial communication. It was observed that the largest share of children
      made use of cardiopulmonary bypass for more than 30 minutes, with a median of 80
      minutes, suffered a median sternotomy, using only the mediastinal drain and made
      use of mechanical ventilation after surgery, with the median about 6.6 hours.
      Only three (8.1%) patients developed pulmonary complications, and of these, two
      died. CONCLUSION: Most of the sample was female, school aged and from the
      countryside. The low time of cardiopulmonary bypass and mechanical ventilation,
      and congenital heart disease with low risk, may have been factors that
      contributed to the low rate of pulmonary complications postoperative.

PMID- 20802918
TI  - Comparative study between on-pump and off-pump coronary artery bypass graft in
      women.
AB  - BACKGROUND: It has been well documented that women have higher morbidity and
      mortality rates than men following coronary artery bypass graft (CABG) surgery.
      In view of this evidence, it is necessary to know if there is benefit to off-pump
      CABG surgery in women in comparison to on-pump CABG. OBJECTIVES: Compare outcomes
      between off-pump CABG and on-pump CABG in women. METHODS: Retrospective study.
      Our investigation analyzes comparatively clinical profile, thirteen procedure
      complications and mortality of a population of 941 consecutive women undergoing
      CABG surgery (549 off-pump and 392 on-pump) at two hospitals for the period
      January 2000 to December 2005. RESULTS: Mortality rate for women undergoing off
      pump CABG surgery is lower than for women undergoing on-pump surgery, however,
      not statistically significant (3.1% vs 5.3%; P=0.134). The complication rates
      analyzed (hemorrhagic shock, neurologic, respiratory, acute renal failure, adult
      respiratory distress syndrome, septicemia, pneumonia, atrial fibrillation) were
      lower (significant statistically difference) for women off-pump than women on
      pump, with the exception of low cardiac output and wound infection. CONCLUSIONS:
      Evidence suggests that off-pump CABG surgery may be better for women than on-pump
      CABG surgery because it appears to reduce morbimortality rates. Ten of 13
      complications investigated demonstrated an advantage for women undergoing off
      pump surgery relative to those receiving on-pump surgery.

PMID- 20802919
TI  - Cannulation tactics in upper ministernotomy for the surgical treatment of
      congenital heart disease.
AB  - INTRODUCTION: The present report describes the technique for "inverted L" upper
      ministernotomy with central canulation for the treatment of simple congenital
      cardiopathies and presents the initial results. METHODS: Ten patients (mean age:
      7 +/- 4.2 years; mean weight 29.1 +/- 13.5 kg) were operated on between January
      2006 and July 2007. RESULTS: All defects were corrected. No death was observed
      and no complication that required reintervention occurred. CONCLUSION: The
      described technique showed to be feasible and safe for the correction of certain
      congenital cardiopathies, with less surgical trauma, besides the aesthetic
      benefit and an expectation of diminished thoracic deformity in the future.

PMID- 20802920
TI  - In situ reconstruction with bovine pericardial tubular graft for aortic graft
      infection.
AB  - Prosthetic graft infection is a serious complication of abdominal aorta surgery.
      Its removal is always indicated because it prevents potential significant
      complications, but reconstruction is a technical challenge. The authors present a
      case of an in situ reconstruction with corrugated bovine pericardial tubular
      graft.

PMID- 20802921
TI  - Supravalvular aortic stenosis surgical repair using modified Sousa's technique.
AB  - Report of a patient with seven years old and effort intolerance progressing. The
      child had tachycardia, pansystolic murmur in the aortic focus. Echocardiography
      showed left ventricle hypertrophy and aortic narrowing at the level of
      sinotubular junction with sistolic gradient of 190 mmHg. Cardiac catheterization
      confirmed the diagnostic suggesting left coronary ostium stenosis. The surgery
      was performed modification the technique, described by Sousa. Immediate post
      operative has presented no complications, with gradient of 23 mmHg, and good
      leaflets mobility.

PMID- 20802922
TI  - Surgical treatment of superior vena cava syndrome caused by invasive thymoma.
AB  - We report on a case of a 57 years-old white male, patient, who presented superior
      vena cava syndrome (SVC) for 3 months, derived from an invasive thymoma in the
      medium and anterior mediastinum, compromising intrinsic and extrinsic to the SVC.
      After evaluation by computed tomography and magnetic angioresonance of the
      thorax, the patient underwent radical resection of the thymoma--bypass from left
      subclavian vein to right atrium, using polytetrafluoroethylene tube. Relevant
      case of invasive thymoma causing the occlusion of SVC. The clinic evolution of
      the patient after 7 months was considered satisfactory.

PMID- 20802923
TI  - Heart transplantation in child with non-compacted myocardium.

PMID- 20802924
TI  - Cardiovascular surgery in Brazil: achievements and opportunities.

PMID- 20802926
TI  - Radius of the vessel, resistance and coronary flow.

PMID- 20802927
TI  - [Half a century of living with Aluizio Prata. A testimonial in honor of his 90
      years].

PMID- 20802928
TI  - Diagnosis of hantavirus infection in humans and rodents in Ribeirao Preto, State
      of Sao Paulo, Brazil.
AB  - INTRODUCTION: Hantavirus pulmonary and cardiovascular syndrome (HPCS) is an
      emerging serious disease in the Americas. Hantaviruses (Bunyaviridae) are the
      causative agents of this syndrome and are mainly transmitted through inhalation
      of aerosols containing the excreta of wild rodents. In the Ribeirao Preto region
      (state of Sao Paulo, Brazil), HPCS has been reported since 1998, caused by the
      Araraquara virus (ARAV), for which Necromys lasiurus is the rodent reservoir.
      This study aimed to show diagnostic results relating to infection in humans and
      rodents, obtained at the Virology Research Center of the Ribeirao Preto School of
      Medicine, University of Sao Paulo, between 2005 and 2008. METHODS: HPCS was
      diagnosed by means of ELISA and/or RT-PCR in 11 (21.2%) out of 52 suspected
      cases, and 54.4% of these were fatal. Furthermore, 595 wild rodents (Necromys
      lasiurus, Akodon sp, Calomys tener and Oligoryzomys sp) were caught between 2005
      and 2008. RESULTS: Fifteen (2.5%) of these rodents presented antibodies for
      hantavirus, as follows: Necromys lasiurus (4%), Calomys tener (1.9%) and Akodon
      sp (1.5%). Nucleotide sequences obtained through RT-PCR from one HPCS patient and
      one Calomys tener rodent were compared with hantavirus sequences from GenBank,
      which showed that both were homologous with ARAV. CONCLUSIONS: This work
      corroborates previous studies showing that ARAV is the hantavirus causing HPCS in
      the Ribeirao Preto region. It also shows that rodents infected with hantavirus
      represent a constant risk of transmission of this virus to man.

PMID- 20802929
TI  - Clinical and epidemiological characterization of dengue hemorrhagic fever cases
      in northeastern, Brazil.
AB  - INTRODUCTION: The dengue hemorrhagic dengue (DHF) remains an important public
      health problem in Brazil. The objective of this study was to analyze the
      epidemiological characteristics of DHF cases during the 2003 epidemic in Ceara.
      METHODS: Suspected DHF cases with onset of symptoms between January and December
      2003 were investigated. RESULTS: 37,964 classic dengue cases and 291 DHF cases
      were reported. Among the cases discarded, 75.5% were serologically positive but
      did not meet the criteria recommended by the World Health Organization (WHO). The
      DHF patients' median age was 30 years (2 - 88). Among the hemorrhagic
      manifestations, petechiae were the most (32.6%) frequent. Cases of
      gastrointestinal bleeding, ascites, pericardial pleural effusion, hepatomegaly,
      hypotension and shock showed higher risk of progression to death (p <0.05).
      CONCLUSIONS: The introduction of a new serotype (DENV-3) in Ceara, which
      encountered a susceptible population and high vector density, may have been the
      primary agent responsible for the magnitude of the epidemic. Timely and
      appropriate medical care, along with an organized care structure are essential
      for reducing its lethality.

PMID- 20802930
TI  - Seroprevalence of cytomegalovirus antibodies in blood donors in southern, Brazil.
AB  - INTRODUCTION: Cytomegalovirus (CMV) infection is a matter of concern for blood
      bank professionals and blood transfusion recipients, especially in cases of
      transfusions to neonates and immunocompromised patients. Thus, the present study
      aimed to determine the seroprevalence of CMV IgG and IgM antibodies among blood
      donors in the city of Lages, in the mountain region of Santa Catarina, southern
      Brazil, and to investigate possible associations between the socioeconomic
      characteristics of donors and CMV serological status. METHODS: A
      seroepidemiological cross-sectional study was conducted on 1,045 blood samples
      from donors that were used in serological screening over a one-year
      investigation. All the analyses were conducted using the microparticle enzyme
      immunoassay with Biokit(R) reagents (Barcelona, Spain), in accordance with the
      manufacturer's instructions. RESULTS: Anti-CMV IgG seroprevalence in the sample
      studied was 96.4% (95% CI: 95.23 - 97.50) and that of anti-CMV IgM was 2.3% (95%
      CI: 1.39 - 3.20). There were no statistically significant associations between
      the presence of antibodies and the socioeconomic characteristics of donors.
      CONCLUSIONS: The blood donors in the study region had high seroprevalence of anti
      CMV IgG. Thus, blood component screening strategies and careful indication for
      blood transfusions require special attention among healthcare professionals as
      part of the actions for prevention and reduction of primary infections caused by
      CMV.

PMID- 20802931
TI  - Level of behavior and knowledge concerning human papillomavirus among university
      students of a nursing college.
AB  - INTRODUCTION: Human pappilomavirus is one of the most common sexually transmitted
      diseases, and persistent HPV infection is considered the most important cause of
      cervical cancer. It is detected in more than 98% of this type of cancer. This
      study aimed to determine the level of knowledge concerning human papillomavirus
      among nursing college students of a private educational institution located in
      the City of Bauru, SP, and correlate their knowledge according to the course
      year. METHODS: A descriptive study with a quantitative approach, performed with a
      questionnaire that permitted the quantification of data and opinions, thus
      guaranteeing the precision of the results without distortions in analysis or
      interpretation. The survey was applied to randomly selected 1st, 2nd, 3rd, and
      4th-year nursing college students. Twenty students from each level were selected
      during August 2009, totaling 80 students of both genders. RESULTS: Observation
      revealed that 4th-year students had greater knowledge than 1st-year students,
      reflecting the greater period of study, the lack of knowledge of 1st-year
      students was due to the low level of information acquired before entering
      college. CONCLUSIONS: The need for complementary studies which determine the
      profile and knowledge of a larger number of teenagers in relation to HPV was
      established. The need for educational programs that can overcome this lack of
      information is undeniable, especially those aimed at making adolescents less
      susceptible to HPV and other STDs.

PMID- 20802932
TI  - Intrahospital spread of carbapenem-resistant Pseudomonas aeruginosa in a
      University Hospital in Florianopolis, Santa Catarina, Brazil.
AB  - INTRODUCTION: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) has been
      isolated with increasing frequency in Brazilian hospitals. Since June 2003, its
      detection in a teaching hospital in the city of Florianopolis, Brazil, has
      increased. This study aimed to investigate the minimal inhibitory concentration
      (MIC), presence of Metallo-beta-lactamase (MbetaL) and a possible clonal
      relationship among the isolates. METHODS: The study included 29 CRPA and seven
      isolates with reduced susceptibility. The MIC was determined by agar-dilution.
      Detection of MbetaL was performed by Double Disk Sinergism (DDS) and Combined
      Disk (CD). The MbetaL gene was verified by PCR and nucleotide sequence analysis.
      Epidemiological typing was performed by pulsed-field gel electrophoresis.
      RESULTS: Among the 29 carbapenem-resistant isolates, polymyxin B presented 100%
      susceptibility and piperacillin/tazobactam 96.7%. Seventeen (62%) strains were
      verified as clonal (A clone) and among these, six isolates indicated
      phenotypically positive tests for MbetaL and harbored the blaSPM-1 gene. The
      first CRPA isolates were unrelated to clone A, harbored blaIMP-16 and were
      phenotypically positive only by CD. CONCLUSIONS: The spread of a high-level of
      resistance clone suggests cross transmission as an important dissemination
      mechanism and has contributed to the increased rate of resistance to carbapenems.
      This study emphasizes the need for continuous surveillance and improved
      strategies.

PMID- 20802933
TI  - [Molecular characterization of carbapenem-resistant and metallo-beta-lactamase
      producing Pseudomonas aeruginosa isolated from blood cultures from children and
      teenagers with cancer].
AB  - INTRODUCTION: The objective of this study was to evaluate the prevalence and
      dissemination of carbapenem-resistant and metallo-beta-lactamase-producing
      Pseudomonas aeruginosa isolated from blood-stream samples (2000-2005) that were
      collected from patients admitted to the Institute of Pediatric Oncology, UNIFESP
      (IOP-GRAACC). METHODS AND RESULTS: Fifty-six P. aeruginosa samples were isolated
      from 49 patients. Thirty-two of these samples were classified as carbapenem
      resistant using the disc diffusion method and were subjected to the PCR reaction
      in order to detect MBL genes. Eighteen of these 32 isolates showed the blaSPM-1
      gene. Eight samples selected in different years over the study period presented
      the same genetic profile according to pulsed-field gel electrophoresis. The
      antimicrobial therapy was considered adequate for only 23.5% of the patients with
      bacteremia due to P. aeruginosa carrying the blaSPM-1 gene, and a high lethality
      rate of 70.6% was observed during the 30-day period after bacteremia and an
      inadequate initial antibiotic regimen. CONCLUSIONS: We detected the presence of a
      clone of carbapenem-resistant P. aeruginosa carrying blaSPM-1 that persisted in
      blood culture samples over a six-year period at the institution, with high
      lethality, thus justifying rigorous epidemiological surveillance and a
      rearrangement of the antimicrobial therapy regimens at the institution.

PMID- 20802934
TI  - High prevalence of methicillin-resistant Staphylococcus aureus with SCCmec type
      III in cystic fibrosis patients in southern, Brazil.
AB  - INTRODUCTION: Bacterial colonization of the lungs is the main cause of morbidity
      in cystic fibrosis (CF). Pathogens such as Staphylococcus aureus are very well
      adapted to the pulmonary environment and may persist for years in the same
      patient. Genetic determinants of these bacteria, such as the presence of SCCmec
      have recently emerged as a problem in this population of patients. METHODS:
      Staphylococcus aureus isolates obtained from different clinical materials coming
      from CF and non-CF patients attended at a cystic fibrosis reference hospital were
      compared according to SCCmec type and antibiotic susceptibility profile. RESULTS:
      Three hundred and sixty-four single-patient Staphylococcus aureus isolates were
      collected, of which 164 (45%) were from CF patients. Among the latter, 57/164
      (44.5%) were MRSA, and among the non-CF patients, 89/200 (35%) were MRSA.
      Associated pathogens were found in 38 CF patients. All 57 MRSA from CF patients
      harbored the multiresistant cassette type III. In contrast, 31/89 MRSA from non
      CF patients harbored SCCmec type I (35%) and 44/89 harbored type III (49%). The
      antibiotic susceptibility pattern was similar between CF and non-CF patients.
      CONCLUSIONS: The high prevalence of multiresistant SCCmec type III among CF
      patients compared with non-CF patients in our institution may make it difficult
      to control disease progression through antibiotic therapy for promoting the
      survival of this kind of patient.

PMID- 20802935
TI  - Antimicrobial resistance and investigation of the molecular epidemiology of
      Listeria monocytogenes in dairy products.
AB  - INTRODUCTION: Listeria monocytogenes is a ubiquitous microorganism in nature and
      is responsible for listeriosis, an infectious disease caused by consumption of
      contaminated food. METHODS: Molecular characterization was performed on 19
      strains of Listeria monocytogenes (serovars 1/2a, 1/2b, 4b and 4c), isolated from
      dairy products in Rio Grande do Sul, Brazil. The molecular techniques applied
      were random amplification of polymorphic DNA and restriction enzyme analysis. In
      addition to the molecular analysis, the antimicrobial resistance profile was
      determined. RESULTS: The strains studied showed a low degree of diversity. In
      relation to the antimicrobial resistance profile of those microorganisms from the
      samples analyzed, all of them were susceptible to the antimicrobials tested.
      CONCLUSIONS: The molecular techniques that were used presented good
      discriminatory power for the strains studied. Furthermore, all of the samples
      that were analyzed were susceptible to the antimicrobials tested.

PMID- 20802937
TI  - Cytokine expression in the duodenal mucosa of patients with visceral
      leishmaniasis.
AB  - INTRODUCTION: Visceral leishmaniasis (VL) is a neglected tropical disease with a
      complex immune response in different organs. This pattern of organ-specific
      immune response has never been evaluated in the gastrointestinal tract. The aim
      of this study was to determine the in situ immune response in duodenal biopsies
      on patients with VL. METHODS: A case-control study was conducted on 13 patients
      with VL in comparison with nine controls. The immune response was evaluated using
      immunohistochemistry, for CD4, CD8, CD68, IL-4, IFN-gamma, TNF-alpha and IL-10.
      Histological findings from the villi, crypts and inflammatory process were
      analyzed. RESULTS: All the cases of VL presented Leishmania antigens. No antigen
      was detected in the control group. The villus size was greater in the VL patients
      (p < 0.05). CD68 (macrophages) and CD4 levels were higher in the VL patients (p <
      0.05). No differences in the expression of CD8, TNF-alpha, IL-10 or IL-4 were
      demonstrated. The number of cells expressing IFN-gamma was lower in the VL
      patients (p < 0.05). CONCLUSIONS: Low levels of cytokines were found in the
      gastrointestinal tract of patients with VL. This pattern was not found in other
      organs affected by the disease. Immunotolerance of this tissue against Leishmania
      could explain these findings, as occurs with intestinal bacteria.

PMID- 20802936
TI  - Is severe visceral leishmaniasis a systemic inflammatory response syndrome? A
      case control study.
AB  - INTRODUCTION: The objective of the study is to identify the main risk factors for
      death by New World visceral leishmaniasis and establish a coherent pathogenic
      substrate of severe disease based on clinical findings. METHODS: Seventy-six
      deceased inpatients and 320 successfully treated inpatients with VL were studied
      in a case control study. RESULTS: Bacterial infection and bleeding were mutually
      exclusive events leading to death. Five risk factors were unique for death by
      bacterial infection (malnutrition, pulmonary rales, severe anemia, severe
      absolute neutropenia and higher neutrophil count), while another six were unique
      for death by bleeding (jaundice, severe relative neutropenia, severe
      thrombocytopenia, liver injury, kidney failure, higher bone marrow parasite
      load). Bacterial infection, bleeding, severe anemia, diarrhea, dyspnea, edema,
      jaundice and bone marrow parasite load were the main syndromes of visceral
      leishmaniasis among successfully treated patients. CONCLUSIONS: The data support
      the idea that bacterial infections are due to immune paralysis. Broad organ and
      system involvement is plausibly due to the high production of proinflammatory
      cytokines, whose actions fit well with visceral leishmaniasis. The syndromes and
      causative mediators are typical of a slowly developing systemic inflammatory
      response syndrome.

PMID- 20802938
TI  - Autochthonous visceral leishmaniasis in Brasilia, Federal District, Brazil.
AB  - INTRODUCTION: Visceral leishmaniasis is a public health threat in Brazil
      considering the high lethality rates and increasing geographical dispersion to
      large urban conglomerates over the past 25 years. This study aimed to confirm
      suspected autochthonous cases of visceral leishmaniasis reported from 2005 to
      2009 among individuals living in Brasilia, Federal District. METHODS: A
      retrospective review of the surveillance data obtained on a regular basis and
      clinical records of the reported cases were performed in 2009. RESULTS: Data from
      entomological and canine surveys revealed the presence of both Lutzomyia
      longipalpis and positive serology for Leishmania in dogs within 19 of the 21
      neighborhoods where human cases occurred since 2005. The review of surveillance
      data and medical records, together with the entomological and canine survey data,
      permitted confirmation of 21 autochthonous human cases in the Federal District.
      The disease predominantly affected children (12/21) and those from the Sobradinho
      region (16/21); the typical presentation of fever, hepatosplenomegaly and
      pancytopenia was observed in 67% of cases. Three deaths occurred during the study
      period. Leishmania (Leishmania) chagasi was successfully isolated from one human
      case and twelve canine cases. CONCLUSIONS: Visceral leishmaniasis should be
      considered endemic in Brasilia based on the documented epidemiological behavior
      herein described and the confirmed autochthony of human cases.

PMID- 20802939
TI  - Seroprevalence and risk factors for canine visceral leishmaniasis in the endemic
      area of Dias D'Avila, State of Bahia, Brazil.
AB  - INTRODUCTION: Visceral leishmaniasis (VL) is an important zoonosis in relation to
      public health systems. Dogs are the main domestic reservoir. This study aimed to
      investigate occurrences of canine VL in Dias D'Avila, State of Bahia, Brazil.
      METHODS: The prevalence was evaluated by means of clinical and laboratory tests
      on a population of 312 domestic dogs from 23 localities in this municipality,
      using indirect immunofluorescence and immunoenzymatic assays. RESULTS: Among the
      animals examined, 3.2% and 6.7% showed signs of VL, confirmed by indirect
      immunofluorescence and immunoenzymatic assays, respectively, with a distribution
      of 29.9% (24 dogs) in the rural zone and 4.9% (288 dogs) in the urban zone (p =
      0.001). The clinical evaluation on seropositive dogs showed both asymptomatic
      animals (2.4%) and symptomatic animals (47.6%), along with other abnormalities
      (e.g. normocytic and normochromic anemia, with leukocytosis and
      thrombocytopenia). Observations relating to phenotypic characteristics (e.g. sex,
      age, breed and hair) did not present statistical significance, although high
      seropositivity among male, short-haired and mixed-breed dogs was observed.
      CONCLUSIONS: The findings showed that VL was a predominantly rural zoonosis and
      that close contact between poultry and domestic dogs significantly increased the
      risk of canine infection in this region.

PMID- 20802940
TI  - Evaluation of the six-minute walk test in patients with chronic heart failure
      associated with Chagas' disease and systemic arterial hypertension.
AB  - INTRODUCTION: To evaluate physical capacity as determined by the six-minute walk
      test (6MWT) in patients with chronic heart failure due to Chagas' disease
      associated with systemic arterial hypertension (Chagas-SAH). METHODS: A total of
      98 patients routinely followed at the Cardiomyopathy Outpatient Service were
      recruited. Of these, 60 (61%) were diagnosed with Chagas disease and 38 (39%)
      with Chagas-SAH. RESULTS: The distance walked during 6 min was 357.9 +/-98 m for
      Chagas-SAH patients and 395.8 +/- 121m for Chagas cardiomyopathy patients (p
      >0.05). In patients with Chagas-SAH, a negative correlation occurred between the
      6MWT and the total score of the Minnesota Living with Heart Failure Questionnaire
      (r= -0.51; p=0.001). No other correlations were determined between 6MWT values
      and continuous variables in patients with Chagas-SAH. CONCLUSIONS: The results of
      the 6MWT in Chagas-SAH patients are similar to those verified in Chagas
      cardiomyopathy patients with chronic heart failure. Coexistence of SAH does not
      seem to affect the functional capacity of Chagas cardiomyopathy patients with
      chronic heart failure.

PMID- 20802941
TI  - Genetic variability among Anopheles species belonging to the Nyssorhynchus and
      Anopheles subgenera in the Amazon region.
AB  - INTRODUCTION: Isoenzymatic analyses were performed involving species of the
      Nyssorhynchus and Anopheles subgenera in order to estimate the intra and
      interspecies genetic variability. METHODS: Mosquitoes were caught at different
      localities in the Amazon region. The collection and rearing of mosquitoes in the
      laboratory followed specific protocols. For the genetic variability analyses, the
      technique of horizontal electrophoresis on starch and starch-agarose gel with
      appropriate buffer systems was used. The alloenzyme variation was estimated using
      the Biosys-1 software. RESULTS: Out of the 13 loci, eight were polymorphic.
      Anopheles nuneztovari presented the largest number of alleles per locus, while
      the smallest number was detected in Anopheles marajoara from Macapa. The largest
      number of polymorphic loci was found for Anopheles marajoara from Maruanum and
      the smallest for Anopheles benarrochi (Guayara Mirim). Anopheles darlingi
      (Macapa) presented the greatest heterozygosity (Ho = 0.167 +/- 0.071), while the
      lowest heterozygosity (Ho = 0.045 +/- 0.019) was observed in Anopheles
      intermedius (Pacoval) of the subgenus Anopheles. Wright's F coefficient revealed
      considerable genetic structuring between the populations of Anopheles darlingi
      (Fst = 0.110) and between the populations of Anopheles marajoara (Fst = 0.082).
      CONCLUSIONS: Considering all the species studied, the genetic distance ranged
      from 0.008 to 1.114. The greatest distance was between Anopheles mattogrossensis
      and Anopheles oswaldoi, while the smallest was between the Anopheles benarrochi
      populations.

PMID- 20802942
TI  - [Influence of previous hepatitis B virus infection on liver fibrosis in patients
      with chronic hepatitis C: a retrospective case series evaluation].
AB  - INTRODUCTION: Hepatitis C is a major cause of liver disease worldwide. Its
      evolutionary course is dynamics and may be influenced by several cofactors. Among
      them, previous hepatitis B virus infection (anti-HBcAg [+] and HBsAg [-]) has
      been associated with worse histological and therapeutic prognosis. This study had
      the objective of independently assessing the relationship between previous
      hepatitis B infection and liver fibrosis in patients with chronic hepatitis C.
      METHODS: The medical records of patients chronically infected with the hepatitis
      C virus who had been seen consecutively during a one-year period at the
      infectious and parasitic diseases outpatient clinic of HC FMUSP were
      retrospectively reviewed in relation to epidemiological, clinical and
      histological data. Analysis on the independence of the previous hepatitis B
      infection was performed using the statistical model of multivariate logistic
      regression. Detection of anti-HBcAg was taken to be the independent variable. The
      outcome was taken to be grade 3 and 4 histopathological abnormality (septa with
      nodule formation and cirrhosis). RESULTS: 145 subjects were evaluated in this
      study. 47.2% of them were anti-HBcAg (+). The main risk factor for infection was
      blood and blood derivative transfusion (35.9%). Findings of anti-HBcAg (+) were
      not related to advanced liver fibrosis, although piecemeal necrosis has been
      found frequently in patients with this serological marker. CONCLUSIONS: Previous
      hepatitis B infection does not seem to increase the structural liver damage
      triggered by chronic hepatitis C virus infection, after statistical control for
      other co-factors capable to impact the natural history of this infection.

PMID- 20802943
TI  - [Decline in the prevalence of HTLV-1/2 among blood donors at the Regional Blood
      Center of the City of Uberaba, State of Minas Gerais, from 1995 to 2008].
AB  - INTRODUCTION: A retrospective study was conducted in order to assess the
      prevalence and factors associated with seropositivity for HTLV-1/2 between 1995
      and 2008 in Uberaba Regional Blood Center, and to describe the seropositive blood
      donors in relation to gender, age, marital status, skin color and origin.
      METHODS: Descriptive statistical analysis, chi-square tests and odds ratios were
      produced to compare proportions, along with scatter charts with linear
      correlation coefficients. RESULTS: Among the donors tested, the prevalence of
      seropositivity for HTLV was found to be 0.02%, with indeterminate results in
      0.09%. There was a significant reduction in seropositivity for HTLV between 2002
      and 2008, compared with the period from 1995 to 2001. Among the seropositive
      individuals, females were significantly predominant. CONCLUSIONS: The gradual
      decrease in seropositivity over this period was attributed to the permanent
      exclusion of seropositive repeat donors and improvement in the clinical screening
      methods and serological tests over the years, with a positive impact on
      transfusion safety.

PMID- 20802944
TI  - [CD4 and CD8 T lymphocytes and NK cells in the stroma of the uterine cervix of
      women infected with human papillomavirus].
AB  - INTRODUCTION: Immune response might be a key element regarding the progression or
      regression of human papillomavirus (HPV) infection in the stroma of the uterine
      cervix. This study aimed to quantify the presence of CD4 and CD8 T lymphocytes
      and NK cells in the cervical stroma, by means of immunohistochemistry, in high
      and low grade lesions in patients infected by HPV METHODS: Fifty-six biopsy
      samples from the uterine cervix were used. Forty-three samples were positive for
      oncogenic high-risk HPV DNA and had a histopathological diagnosis of high and low
      grade cervical intraepithelial neoplasia (CIN) or negative for intraepithelial
      lesion and malignancy (NILM); while the other 13 samples were negative for HPV
      DNA with a histopathological diagnosis of NILM RESULTS: Higher quantities of CD4
      T lymphocytes were observed in CIN II/III, carcinoma and NILM samples (p = 0.04)
      and in those in which the viral load was between 10 and 1.000 RLU/PCB. CD8 T
      lymphocytes were predominant in CIN II/III samples (p = 0.02) and also in samples
      with viral loads between 100 and 1,000 RLU/PCB. NK cells predominated in samples
      with low-grade lesions and low viral load CONCLUSIONS: This study proved that in
      the initial stages of the infection, in which no high-grade cell abnormalities
      have yet occurred, no cells that might trigger the effector phase of the immune
      response.

PMID- 20802945
TI  - [ESBL-producing enterobacteria in Passo Fundo, state of Rio Grande do Sul,
      Brazil].
AB  - INTRODUCTION: The main emerging resistance mechanism relating to
      Enterobacteriaceae is represented by production of extended spectrum beta
      lactamases (ESBLs). These enzymes have the capacity to hydrolyze broad-spectrum
      cephalosporins and are greatly used for antimicrobial chemotherapy on
      enterobacterial infections. Although resistance to these agents presents
      remarkable geographical variability, the resistance rates are high in many
      countries METHODS: A retrospective observational cross-sectional descriptive
      study was developed to evaluate the frequency of ESBLs among Enterobacteriaceae
      strains obtained from Hospital Sao Vicente de Paulo, Brazil RESULTS: ESBL
      production was noted in 24.8% (n = 208/838) of the isolates evaluated. Isolates
      of Escherichia coli represented 46.2% (n = 96/208) of the ESBL producers,
      followed by Enterobacter species (30.3%; n = 63/208). The sensitivity of these
      isolates to meropenem was 91.4% and to piperacillin/tazobactam, 67.4%
      CONCLUSIONS: The ESBL levels founded confirm the worldwide concern regarding this
      resistance mechanism.

PMID- 20802946
TI  - [Spatial analysis on childhood tuberculosis in the state of Espirito Santo,
      Brazil, 2000 to 2007].
AB  - INTRODUCTION: Childhood tuberculosis is responsible for 15% of case
      notifications. The focus of Tuberculosis Control National Program is on
      identifying tuberculosis in adults, while leaving children under 15 years of age
      on the margins of studies, diagnoses and treatment. Spatial analysis quantifies
      the exposition to the illness and displays the main causes relating to
      geographical space. The objective of this study was to analyze the spatial
      distribution of childhood tuberculosis in Espirito Santo, between 2000 and 2007,
      according to the municipality of notification METHODS: An ecological study was
      conducted on 515 cases of childhood tuberculosis that occurred between 2000 and
      2007. The Local Empirical Bayesian Method was used to measure the risk. The Moran
      Local Index was calculated in order to evaluate autocorrelations between
      threshold districts RESULTS: High incidence rates were found in the Metropolitan
      Region of Vitoria and the northeastern region, and lower rates were found in the
      southeastern region. Similar data were observed in a study on endemic
      tuberculosis among adults in Espirito Santo. This is possibly related to contacts
      within the home CONCLUSIONS: This study identified possible areas of recent
      transmission of the disease. It is important to emphasize that knowledge of the
      high priority areas for tuberculosis control may help public administrators to
      diminish healthcare iniquities and enable improvement of resources and teams for
      controlling childhood tuberculosis.

PMID- 20802948
TI  - Epidemiology of extended spectrum beta-lactamase producing Enterobacter
      bacteremia in a brazilian hospital.
AB  - INTRODUCTION: Enterobacter can be included in the group of extended spectrum beta
      lactamases (EBSL)-producing bacteria, though few studies exist evaluating risk
      factors associated with this microorganism. A retrospective cohort study was
      conducted to determine risk factors associated with ESBL-producing-Enterobacter
      and mortality METHODS: A retrospective cohort study with 58 bacteremia caused by
      ESBL-producing-Enterobacter (28 cases) and non-ESBL (30 cases) RESULTS: Risk
      factors associated with ESBL-Enterobacter were trauma, length of hospitalization,
      admission to the intensive care unit, urinary catheter and elective surgery (p<
      0.05). The survival curves were similar for ESBL and non-ESBL CONCLUSIONS: ESBL
      producing-Enterobacter bacteremia is prevalent and the survival curve was similar
      to non-ESBL-producing strains.

PMID- 20802947
TI  - [The efficacy of adefovir dipivoxil, entecavir and telbivudine for chronic
      hepatitis B treatment: a systematic review].
AB  - INTRODUCTION: Chronic hepatitis B is one of the most frequent infectious disease
      in the world and represents a serious problem of public health METHODS: A
      systematic review of randomized clinical trials was conducted to evaluate the
      efficacy of the nucleoside/nucleotide analogues (adefovir, entecavir and
      telbivudine) used for the treatment of chronic hepatitis B. The databases PubMed
      and LILACS were consulted, among others RESULTS: Twenty nine articles published
      between January/1970 to December/2009 were selected CONCLUSIONS: All
      nucleoside/nucleotide analogues demonstrate upper or similar efficacy to
      lamivudine. The entecavir can be appropriate for patients with chronic hepatitis
      B, HBeAg positive and negative treatment-naive as alternative to lamivudine,
      considering its low potential of viral resistance. The addition of adefovir to
      lamivudine presented good results in lamivudine resistant patients. The use of
      entecavir and telbivudine in those patients presents risk of crossed resistance.
      TBV is one of the most recent antivirals available, but antiviral resistance
      already documented represents limitation to its use as therapeutic option to LAM.
      Adverse events of nucleoside/nucleotide analogues were similar in
      characteristics, gravity and incidence when compared to the lamivudina and
      placebo.

PMID- 20802949
TI  - Epidemiological profile of acute bacterial meningitis in the state of Rio Grande
      do Norte, Brazil.
AB  - INTRODUCTION: Acute bacterial meningitis (ABM) remains a public health problem in
      Brazil. To evaluate the epidemiology of ABM cases at Giselda Trigueiro Hospital,
      Rio Grande do Norte, a descriptive retrospective survey was conducted covering
      2005 to 2008. METHODS: Clinical and laboratory data were collected from the
      epidemiology department of the hospital and analyzed. RESULTS: Out of 168 ABM
      cases, 24.4%, 10.7%, and 2.4% were, respectively, caused by Streptococcus
      pneumoniae, Neisseria meningitidis and Haemophilus influenza b, and 5.4% by other
      bacteria. The mean age was 22.48 +/- 18.7 years old. CONCLUSIONS: Streptococcus
      pneumoniae was the main causative pathogen in the young urban population.

PMID- 20802950
TI  - A list of mosquito species of the Brazilian State of Pernambuco, including the
      first report of Haemagogus janthinomys (Diptera: Culicidae), yellow fever vector
      and 14 other species (Diptera: Culicidae).
AB  - INTRODUCTION: Besides mosquito species adapted to urban environments (Culex
      quinquefasciatus, Aedes aegypti and Aedes albopictus), only 15 species of
      Anopheles had been recorded in the State of Pernambuco. METHODS: Human-landing
      mosquitoes were collected in Dois Irmaos Park, in Recife. RESULTS: The first
      report for the state of Haemagogus janthinomys, an important vector of yellow
      fever virus, and 14 other species, including Trichoprosopon lampropus, a first
      reported for Brazil. CONCLUSIONS: The mosquito fauna in the area is diversified
      and has potential medical and veterinary importance.

PMID- 20802951
TI  - [Evaluation of the degree of incapacity of patients with a diagnosis of leprosy
      at a dermatology service in the state of Sao Paulo].
AB  - IINTRODUCTION: Leprosy is a chronic infectious disease that can lead to physical
      incapacity. METHODS: The medical records of 167 patients diagnosed with leprosy
      between 2003 and 2007 were reviewed. RESULTS: Most of the patients (60%)
      presented physical incapacity at the time of diagnosis: 34% with grade I and 26%
      with grade II. It was observed that the degree of incapacity had a direct
      correlation with the duration of the disease. CONCLUSIONS: Leprosy is still
      diagnosed late, which may contribute towards maintaining this endemic disease.

PMID- 20802952
TI  - [Investigation of metallo-beta-lactamase-producing Acinetobacter sp and
      Pseudomonas aeruginosa at an emergency hospital in Porto Alegre, State of Rio
      Grande do Sul, Brazil].
AB  - INTRODUCTION: The appearance of metallo-beta-lactamase (MBL)-producing
      Pseudomonas aeruginosa and Acinetobacter sp. is a challenge for hospitals.
      METHODS: The production of MBL in clinical isolates of Pseudomonas aeruginosa and
      Acinetobacter sp. From an emergency hospital in Porto Alegre was investigated
      using the disk approximation test and MBL E-test. The bla genes were determined
      using PCR. RESULTS: Two strains of Pseudomonas aeruginosa and eight of
      Acinetobacter sp were shown to be MBL phenotypes. Amplification of the blaSPM-1
      gene confirmed the presence of the enzyme in P. aeruginosa. CONCLUSIONS: Caution
      is needed in evaluating phenotype tests used for routine detection of metallo
      beta-lactamases.

PMID- 20802953
TI  - HTLV-1 associated myelopathy diagnosed during lepromatous leprosy reaction
      treatment: a case report.
AB  - Leprosy and human T cell lymphotropic virus type 1 infection are prevalent in
      Brazil. Coinfection by Mycobacterium leprae and HTLV-1 is reviewed and a case is
      reported. A 59 year-old woman was followed and HTLV-1 associated myelopathy was
      diagnosed during leprosy treatment. The clinical and neurological aspects of this
      unusual association were initially reviewed. Immunological markers and the
      possible prognoses due to the association of the diseases were discussed. The
      unexpected association of leprosy and HTLV-1 associated myelopathy may occur in
      endemic areas and causes difficulties in determining the correct diagnosis and
      adequate management of the neurological manifestations.

PMID- 20802954
TI  - Recurrent Acremonium infection in a kidney transplant patient treated with
      voriconazole: a case report.
AB  - Acremonium infection is rare and associated with immunosuppression. A case of
      recurrent cutaneous Acremonium infection after short term voriconazole use is
      described. Surgical resection was the definitive therapy. Oral voriconazole was
      used in the treatment of Acremonium infection, but recurrence was associated with
      short therapy. Prolonged antifungal therapy and surgical resection are discussed
      for the treatment of localized lesions.

PMID- 20802955
TI  - Cryptococcus gattii meningoencephalitis in an HIV-negative patient from the
      Peruvian Andes.
AB  - We report a case of an immunocompetent Peruvian patient from the Andes with a one
      month history of meningoencephalitis. Cryptococcus gattii was identified from a
      cerebrospinal fluid culture through assimilation of D-proline and D-tryptophan as
      the single nitrogen source. Initially, the patient received intravenous
      antifungal therapy with amphotericin B. The patient was discharged 29 days after
      hospitalization and continued with oral fluconazole treatment for ten weeks.
      During this period, the patient showed clinical improvement with slight right
      side residual weakness. Through this case report, we confirm the existence of
      this microorganism as an infectious agent in Peru.

PMID- 20802956
TI  - [Traveler's fever associated with cervical adenomegaly and antibodies for
      Bartonella sp in a Brazilian patient returning from South Africa].
AB  - A large number of travelers visit the African continent annually for studying,
      tourism or business reasons. The authors report a case of cervical adenomegaly,
      hepatomegaly and splenomegaly associated with a two-week history of fever and
      seropositivity for Bartonella sp in a 22-year-old female patient who returned
      from South Africa after field work with primates in a wild area.

PMID- 20802958
TI  - [Are extra-Amazonian physicians prepared to diagnose and treat malaria?].

PMID- 20802957
TI  - [Amyloidosis and end-stage renal disease associated with leprosy].
AB  - Renal involvement in leprosy includes glomerulonephritis, amyloidosis and
      tubulointerstitial nephritis. A 58-year-old man was admitted with complaints of
      lower limb edema and dyspnea. At admission, nitrogen retention, anemia,
      hyperkalemia and metabolic acidosis were observed, requiring hemodialysis. The
      patient had a history of lepromatous leprosy. A renal biopsy was performed that
      was compatible with amyloidosis. The patient had a stable outcome, but without
      renal function recovery and remained on regular hemodialysis. Leprosy should be
      investigated in every patient with renal function loss, particularly in those
      with cutaneous lesions or other manifestations suggestive of leprosy.

PMID- 20802959
TI  - [Visceral leishmaniasis and malnutrition: a relation much neglected].

PMID- 20802960
TI  - Paracoccidioidomycosis: the dimension of the problem of a neglected disease.

PMID- 20802961
TI  - An atypical presentation of cutaneous leishmaniasis.

PMID- 20802962
TI  - [Cardiovascular responses to resistance exercise are affected by workload and
      intervals between sets.]
AB  - BACKGROUND: The control of cardiovascular responses during resistance exercise
      (RE) is important for patient safety. OBJECTIVE: To investigate the influence of
      repetition maximum (RM) and rest interval between sets (RI) on heart rate (HR),
      systolic blood pressure (SBP) and rate-pressure product (RPP) during RE. METHODS:
      Twenty healthy subjects (26 +/- 5 years of age) underwent RE protocols involving
      three sets of leg press (6 and 12 RM) and RI proportional to the contraction time
      (1:3 and 1:5). The HR was checked on a continuous basis by using a
      cardiotachometer and the SBP was checked at the end of the sets, via a protocol
      validated by the auscultatory method. RESULTS: The HR was influenced by the
      workload (p = 0.008) and sets (p < 0.001), but not by the RI (p = 0.087). The SBP
      suffered from the isolated effect of the number of sets (p < 0.001) and RI (p =
      0.017), but not from the workload (p = 0.95). The RPP rose in direct proportion
      to the workload (p = 0.036) and sets (p < 0.001), but in inverse proportion to
      the RI (p = 0.006). In 6 RM protocols, the variation in the HR was higher for RI
      = 1:3 (Delta = 11.2 +/- 1.1 bpm) than for RI = 1:5 (Delta = 4.5 +/- 0.2 bpm; p =
      0.002), but there was no difference for 12 RM (Delta 1:3 = 21.1 +/- 2.2 bpm;
      Delta 1:5 = 18.9 +/- 2.0 bpm, p = 0.83). The RI influenced the variation in SBP
      in all loads (6 RM - Delta 1:3 = 10.6 +/- 0.9 mmHg, Delta 1:5 = 6.6 +/- 0.7 mmHg;
      p = 0.02 and 12 RM - Delta 1:3 = 15.2 +/- 1.1 mmHg, Delta 1:5 = 8.4 +/- 0.7 mmHg;
      p = 0.04). The RPP rose in proportion to the workload (p = 0.036) and to the sets
      (p < 0.001), but in inverse proportion to the RI (p = 0.006). With RI = 1:3,
      there was difference in RPP for 6 RM (Delta = 2,892 +/- 189 mmHg.bpm) and 12 RM
      (Delta = 4,587 +/- 300 mmHg.bpm; p = 0.018), but not with RI = 1:5 (6 RM: Delta =
      1,224 +/- 141 mmHg.bpm, 12 RM: Delta = 2,332 +/- 194 mmHg.bpm; p = 0.58).
      CONCLUSION: Regardless of the workload, an increased RI was associated with lower
      cardiovascular responses during RE, especially of SBP.

PMID- 20802963
TI  - [Anemia in patients with advanced heart failure].
AB  - BACKGROUND: anemia is linked with worsening of progress in patients with heart
      failure (HF). However, there are few studies of anemia in patients with advanced
      HF. OBJECTIVE: to evaluate the characteristics of anemia in HF at an advanced
      stage. METHODS: the study included 99 patients, aged > 18 and LVEF < 45%, who
      were hospitalized for HF compensation (FC IV/NYHA). Patients with hemoglobin (Hb)
      levels < 12 g/dl were considered anemic. Data on anemic and nonanemic patients
      were compared. The Student's t-test, Chi-square test and Fisher test were used.
      The relative risk (HF 95%) was calculated by the Cox regression. RESULTS: on
      average, the patients were monitored for 10.8 months (8.9), and 34.3% of patients
      with HF had anemia. On average, in comparison with nonanemic patients, anemic
      patients were older (64.1 +/- 15.6 versus 54.8 +/- 12.9 years old, p = 0.004),
      their creatinine level was higher (1.9 +/- 1 versus 1.5 + 0.5 mg/dl, p = 0.018)
      and their BNP level was also higher (2,077.4 +/- 1,979.4 versus 1,212.56 +/-
      1,080.6 pg/ml, p = 0.026). 38.24% of the anemic patients had iron deficiency
      anemia. After there was an improvement in the congestion, only 25% of patients
      with anemia were discharged with Hb > 12 g/dl. Anemia was an independent marker
      of poor prognosis in the multivariate analysis (mortality of 47% vs 24.6%, p =
      0.016, relative risk of 2.54). CONCLUSION: anemia affects approximately one third
      of patients with advanced HF, and iron deficiency is an important etiology.
      Anemic patients are older their renal function was more deteriorated. The
      improvement in the congestion was not enough to improve the anemia in most cases.
      In patients with advanced HF, anemia is an independent marker of poor prognosis.

PMID- 20802964
TI  - Pressure response after resistance exercise for different body segments in
      hypertensive people.
AB  - BACKGROUND: Resistance exercise has now been recommended as adjunct component of
      aerobic exercise on physical training program directed to the treatment and
      control of hypertension (HBP). However, it has not been widely incorporated yet
      into clinical practice, possibly by the scarcity of available evidence regarding
      the safe limits of the acute pressure response in this modality. OBJECTIVE: To
      investigate the acute effect of progressive resistance exercise of different body
      segments, the pressure response of patients with controled hypertension (HBP).
      METHODS: Twenty-five patients (14 women) with controled hypertension with
      medication (64.5 +/- 10.8 years old) and sedentary, had three visits to a
      randomic progressive resistance exercise session, in the following muscle groups:
      femoral quadriceps, latissimus dorsi and brachial biceps. Blood pressure
      measurements were obtained at all visits at rest, immediately after each series
      of exercise and after 5 minutes of recovery. RESULTS: Immediately after acute
      resistance exercise, a significant increase in systolic blood pressures, without
      significant changes of diastolic pressure compared to pressure levels at rest for
      all muscle groups and for all intensities studied. Additionally, there was a
      greater tendency to elevation of systolic pressure when the femoral quadriceps
      muscle was exercised at high intensity. CONCLUSION: Resistance exercise in
      different body segments promoted similar increases and safe levels of systolic
      blood pressure, although with a tendency toward greater response of it when large
      muscle groups at high loads are exercised.

PMID- 20802965
TI  - [Oculo-auriculo-vertebral spectrum in patients with congenital heart defects].
AB  - BACKGROUND: there have been few studies evaluating the frequency of oculo
      auriculo-vertebral spectrum (OAVS) in patients with congenital heart defects
      (CHDs). OBJECTIVE: to verify the frequency of OAVS in a sample of patients with
      major heart malformations. METHODS: we evaluated a prospective cohort of patients
      with CHD admitted in a pediatric cardiac intensive care unit (ICU) in Brazil. The
      diagnosis of OAVS was made based on the clinical data, considering standard
      criteria. The patients that met these criteria were submitted to high resolution
      GTG-Banding karyotype and fluorescence in situ hybridization for 22q11.2
      microdeletion. Fisher's exact test (P < 0.05) was used for the statistical
      analysis. RESULTS: During the period of evaluation, 330 patients were
      hospitalized for the first time in the ICU, but thirty of them did not
      participate in the study. Of the 300 patients that constituted the final sample,
      OAVS was verified in 3 cases (1%). All presented normal cytogenetic studies.
      CONCLUSION: OAVS seems to be a frequent condition among patients with CHDs.
      However, we cannot exclude the possibility that the frequency of OAVS found in
      our study might have been underestimated due to the low rate of prenatal
      detection of CHDs and the limited access of patients to appropriate health care
      in our region. Future prospective studies with well defined clinical criteria and
      subjects with mild and major defects will be important to assess the role of OAVS
      in the general population of subjects with heart malformations.

PMID- 20802966
TI  - [Incidence of pulmonary complications in myocardial revascularization].
AB  - BACKGROUND: despite the increasingly careful attempts to reduce perioperative
      risks, pulmonary complications following surgery are still very common, leading
      to longer length of hospital stays or death. OBJECTIVE: to describe the incidence
      of pulmonary complications and identify their association with duration of
      extracorporeal circulation (ECC), surgery and ischemia, number of bypass grafts
      performed, location of drains and length of drainage following myocardial
      revascularization (MRV). METHODS: this contemporaneous cohort consisted of 202
      patients undergoing elective myocardial revascularization (MRV) with saphenous
      vein graft and internal mammary artery graft and ECC, at a referral university
      cardiology hospital in Southern Brazil, from April 2006 to November 2007. The
      following outcomes were analyzed: duration of mechanical ventilation; pneumonia
      onset; atelectasis; pleural effusion; location of drains and time of removal; and
      length of hospital stay. RESULTS: of the 202 patients, 90 developed some sort of
      pulmonary complication. The incidence of pleural effusion was 84%, whereas
      atelectasis was 65%. The following variables were associated with pulmonary
      complications: duration of ECC (p = 0.003), surgery (p = 0.040) and ischemia (p =
      0.001); length of drainage (p = 0.050) and location of pleural drains (p =
      0.033); age (p = 0.001); ejection fraction (p = 0.010); diagnosis of asthma (p =
      0.047) and preoperative abnormal chest X-ray findings (p = 0.029). CONCLUSION:
      variables related to the complexity of the surgery and preexisting comorbidities
      are associated with a high incidence of postoperative pulmonary complications.
      These data reinforce the importance of having patients undergo perioperative
      clinical assessment to detect early respiratory complications after MRV.

PMID- 20802968
TI  - [Arterial hypertension and its correlation with some risk factors in a small
      brazilian town].
AB  - BACKGROUND: arterial hypertension (AH) is a health problem that affects a large
      number of undiagnosed or inadequately treated hypertensive individuals and
      presents a high rate of treatment nonadherence. OBJECTIVE: to estimate the
      prevalence of AH and its correlation with some cardiovascular risk factors among
      the adult population of the town of Firminopolis, state of Goias, Brazil.
      METHODS: descriptive, observational and cross-sectional population-based study of
      a simple random sample (age > 18 years): standardized questionnaires with blood
      pressure (BP) measurements (AH criterion: BP > 140 x 90 mmHg), weight, height,
      Body Mass Index (BMI) and waist circumference (WC). Data were stored (Microsoft
      Access) and analyzed using Epi-info software. RESULTS: we evaluated 1,168
      individuals, with a predominance of the female sex - 63.2% and a mean age of 43.2
      +/- 14.9 years. There was a prevalence of overweight in 33.7% of the individuals
      and obesity in 16.0% of the individuals. There was a prevalence of altered WC in
      51.8% demand of smoking in 23.2%. A sedentary life style at work and leisure
      activities was present in 67.6% and 64.8% of the individuals, respectively, with
      a higher proportion seen among the women. Alcohol consumption was observed in
      33.3% of the sample. The prevalence of AH was 32.7%, higher among the men (35.8%)
      than among the women (30.9%). A positive correlation with AH was identified with
      BMI, WC and age range. A negative correlation was observed between AH and level
      of schooling, with 18.2% of hypertensive individuals with 9 or more years of
      schooling. CONCLUSION: a high prevalence of AH, overweight and WC alteration was
      identified. The female sex represented a protective factor for the risk of AH. A
      positive correlation was found between AH and BMI, WC and age range; a negative
      correlation was identified between AH and level of schooling.

PMID- 20802967
TI  - [Influence of subclinical atherosclerosis on diastolic function in individuals
      free of cardiovascular disease].
AB  - BACKGROUND: it is plausible that subclinical atherosclerosis alters coronary
      reserve and impairs diastolic function of the left ventricle. However, the
      relationship between subclinical stages of atherosclerosis and diastolic function
      has not been established in subjects free of cardiovascular disease. OBJECTIVE:
      to test the hypothesis that subclinical atherosclerosis has a negative
      association with diastolic function. METHODS: individuals > 35 years old, free of
      cardiovascular disease, with normal blood pressure and negative treadmill stress
      test, were selected to have common carotid intima-media thickness (IMT) assessed
      by ultrasound and parameters of diastolic function by echocardiography, primarily
      tissue Doppler E'/A' ratio. RESULTS: forty-eight subjects were studied, aged 56
      +/- 10 years, 67% females. Composite common carotid IMT had a significant
      negative correlation with tissue Doppler E'/A' ratio (r = - 0.437, p = 0.002).
      Individuals in the fourth quartile of IMT had a significant lower tissue Doppler
      E'/A' ratio (0.76 +/- 0.25), as compared with the first (1.2 +/- 0.29), second
      (1.2 +/- 0.36) and third quartiles (1.1 +/- 0.25) - p = 0.002. Composite common
      carotid IMT in the fourth quartile (> 0.8 mm) independently predicted E'/A' ratio
      (p = 0.02), after adjustment for potentially confounding variables, such as age,
      female gender, waist circumference, diastolic blood pressure, HDL-cholesterol and
      Framingham Risk. CONCLUSION: early stage of subclinical atherosclerotic disease
      is negatively associated with diastolic function parameters in healthy
      individuals, regardless of age and clinical characteristics.

PMID- 20802971
TI  - Protective effect of maternal prenatal melatonin administration on rat pups born
      to mothers submitted to constant light during gestation.
AB  - We studied the effects of adverse conditions such as constant light (LL) on the
      circadian rhythm of malate (MDH, EC 1.1.1.37) and lactate (LDH, EC 1.1.1.27)
      dehydrogenase activities of the testes of male Wistar rats on postnatal day 28
      (PN28), anxiety-like behavior (elevated plus-maze test) at PN60 and sexual
      behavior at PN120. The rats were assigned to mother groups on day 10 of
      pregnancy: control (12-h light/dark), LL (light from day 10 to 21 of pregnancy),
      and LL+Mel (LL and sc injection to the mothers of a daily dose of melatonin, 1
      mg/kg body weight at circadian time 12, from day 17 to 21 of pregnancy). LL
      offspring did not show circadian rhythms of MDH (N = 62) and LDH (N = 63)
      activities (cosinor and ANOVA-LSD Fisher). They presented a 44.7% decrease in
      open-arm entries and a 67.9% decrease in time (plus-maze test, N = 15, P < 0.001,
      Mann-Whitney U-test and Kruskal-Wallis test), an increase in mounting (94.4%),
      intromission (94.5%) and ejaculation (56.6%) latencies (N = 12, P < 0.01, Mann
      Whitney U-test and Kruskal-Wallis test) and lower numbers of these events (61, 59
      and 73%, respectively; P < 0.01, N = 12) compared to controls. The offspring of
      the LL+Mel group presented MDH and LDH circadian rhythms (P < 0.05, N = 50,
      cosinor and ANOVA-LSD Fisher), anxiety-like and sexual behaviors similar to
      control. These findings supported the importance of the melatonin signal and
      provide evidence for the protective effects of hormones on maternal programming
      during gestation. This protective action of melatonin is probably related to its
      entrainment capacity, favoring internal coupling of the fetal multioscillatory
      system.

PMID- 20802969
TI  - [Chagas cardiomyopathy: prognosis in clinical and hemodynamic profile C].
AB  - BACKGROUND: patients with heart failure (HF) who are admitted showing poor
      perfusion and congestion (clinical-hemodynamic profile C) are the group that
      evolves with the worst prognosis in decompensated heart failure. However, there
      is little information in literature on the etiology of cardiopathy influences the
      outcome of patients in advanced stage. OBJECTIVE: to assess the outcome of
      patients admitted with clinical and hemodynamic profile C and verify the role of
      the etiology in this phase. METHODS: a cohort study was performed including
      patients with left ventricle ejection fraction (LVEF) < 45.0%, functional class
      IV and hospitalization presenting clinical-hemodynamic profile C. The group was
      divided into patients with chagasic (Ch) and non chagasic (NCh) cardiomyopathy.
      Statistical analysis used Student t test, Fisher exact test, chi-square and SPSS
      tests. The significance of p < 0.05 was considered. RESULTS: one hundred
      patients, with mean age 57.6 +/- 15.1 years and mean LVEF of 23.8 +/- 8.5%, were
      included. Among the patients studied, 33.0% were chagasic and, in comparison with
      NCh, had lower systolic blood pressure (Ch 89.3 +/- 17.1 mmHg versus NCh 98.8 +/-
      21.7 mmHg, p = 0.03 ) and lowest average age - Ch 52.9 +/- 14.5 years versus NCh
      59.8 +/- 14.9 years, p = 0.03). During follow-up of 25 months, mortality was
      66.7% for Ch and 37.3% in NCh (p = 0.019). The Chagas disease etiology was an
      independent marker of poor prognosis in multivariate analysis with risk ratio of
      2.75 (HF 95.0%, from 1.35 to 5.63). CONCLUSION: in patients with advanced HF,
      Chagas disease is an important predictor of the worst prognosis.

PMID- 20802972
TI  - Caspase dependence of the death of neonatal retinal ganglion cells induced by
      axon damage and induction of autophagy as a survival mechanism.
AB  - We examined the degeneration of post-mitotic ganglion cells in ex-vivo neonatal
      retinal explants following axon damage. Ultrastructural features of both
      apoptosis and autophagy were detected. Degenerating cells reacted with antibodies
      specific for activated caspase-3 or -9, consistent with the presence of caspase
      activity. Furthermore, peptidic inhibitors of caspase-9, -6 or -3 prevented cell
      death (100 uM Ac-LEDH-CHO, 50 uM Ac-VEID-CHO and 10 uM Z-DEVD-fmk, respectively).
      Interestingly, inhibition of autophagy by 7-10 mM 3-methyl-adenine increased the
      rate of cell death. Immunohistochemistry data, caspase activation and caspase
      inhibition data suggest that axotomy of neonatal retinal ganglion cells triggers
      the intrinsic apoptotic pathway, which, in turn, is counteracted by a pro
      survival autophagic response, demonstrated by electron microscopy profiles and
      pharmacological autophagy inhibitor.

PMID- 20802973
TI  - Caspase-8 and p38MAPK in DATS-induced apoptosis of human CNE2 cells.
AB  - Nasopharyngeal carcinoma is a common malignancy in Southern China of uncertain
      etiologic origin. Diallyl trisulfide (DATS), one of the major components of
      garlic (Allium sativum), is highly bactericidal and fungicidal. In this study, we
      investigated the function of p38 mitogen-activated protein kinase (MAPK) and
      caspase-8 in DATS-induced apoptosis of human CNE2 cells using MTT [3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], flow cytometry assay, and
      Western blotting. After CNE2 cells were treated with DATS (50, 100, or 150 MUM)
      for 24 h, cell viability rates were 75.9, 63.4 and 39.6%, and apoptosis rates
      were 24.5, 36.9, and 62.4%, respectively. The data showed that DATS induced CNE2
      cell death in a dose-dependent manner. After human CNE2 cells were treated with
      100 MUM DATS and inhibitors (10 MUM SB203580 and Z-LETD-FMK for p38MAPK and
      caspase-8, respectively), changes in cell viability and apoptosis and in p38MAPK
      and caspase-8 activity were detected. Cell viability rates were 66.5 and 68.1%
      and decreased 9.9 and 11.5% compared with inhibitor treatment alone. Apoptosis
      rates were 31.53 and 29.98% and increased 9.1 and 10% compared with inhibitor
      treatment alone. The results indicated that DATS activates p38MAPK and caspase-8,
      but both inhibitors have an effect on P38MAPK and caspase-8 activity. In
      conclusion, our data indicate that p38MAPK and caspase-8 are involved in the
      process of DATS-induced apoptosis in human CNE2 cells and interact with each
      other.

PMID- 20802974
TI  - Modulation of rhodopsin gene expression and signaling mechanisms evoked by
      endothelins in goldfish and murine pigment cell lines.
AB  - Endothelins (ETs) and sarafotoxins (SRTXs) belong to a family of vasoconstrictor
      peptides, which regulate pigment migration and/or production in vertebrate
      pigment cells. The teleost Carassius auratus erythrophoroma cell line, GEM-81,
      and Mus musculus B16 melanocytes express rhodopsin, as well as the ET receptors,
      ETB and ETA, respectively. Both cell lines are photoresponsive, and respond to
      light with a decreased proliferation rate. For B16, the doubling time of cells
      kept in 14-h light (14L):10-h darkness (10D) was higher compared to 10L:14D, or
      to DD. The doubling time of cells kept in 10L:14D was also higher compared to DD.
      Using real-time PCR, we demonstrated that SRTX S6c (12-h treatment, 100 pM and 1
      nM; 24-h treatment, 1 nM) and ET-1 (12-h treatment, 10 and 100 pM; 24- and 48-h
      treatments, 100 pM) increased rhodopsin mRNA levels in GEM-81 and B16 cells,
      respectively. This modulation involves protein kinase C (PKC) and the mitogen
      activated protein kinase cascade in GEM-81 cells, and phospholipase C, Ca(2+),
      calmodulin, a Ca(2+)/calmodulin-dependent kinase, and PKC in B16 cells. Cells
      were kept under constant darkness throughout the gene expression experiments.
      These results show that rhodopsin mRNA levels can be modulated by SRTXs/ETs in
      vertebrate pigment cells. It is possible that SRTX S6c binding to the ETB
      receptors in GEM-81 cells, and ET-1 binding to ETA receptors in B16 melanocytes,
      although activating diverse intracellular signaling mechanisms, mobilize
      transcription factors such as c-Fos, c-Jun, c-Myc, and neural retina leucine
      zipper protein. These activated transcription factors may be involved in the
      positive regulation of rhodopsin mRNA levels in these cell lines.

PMID- 20802975
TI  - Characterization of angiotensin-converting enzymes 1 and 2 in the soleus and
      plantaris muscles of rats.
AB  - Angiotensin-converting enzymes 1 (ACE1) and 2 (ACE2) are key enzymes of the renin
      angiotensin system, which act antagonistically to regulate the levels of
      angiotensin II (Ang II) and Ang-(1-7). Considerable data show that ACE1 acts on
      normal skeletal muscle functions and architecture. However, little is known about
      ACE1 levels in muscles with different fiber compositions. Furthermore, ACE2
      levels in skeletal muscle are not known. Therefore, the purpose of this study was
      to characterize protein expression and ACE1 and ACE2 activities in the soleus and
      plantaris muscles. Eight-week-old female Wistar rats (N = 8) were killed by
      decapitation and the muscle tissues harvested for biochemical and molecular
      analyses. ACE1 and ACE2 activities were investigated by a fluorometric method
      using Abz-FRK(Dnp)P-OH and Mca-YVADAPK(Dnp)-OH fluorogenic substrates,
      respectively. ACE1 and ACE2 protein expression was analyzed by Western blot. ACE2
      was expressed in the skeletal muscle of rats. There was no difference between the
      soleus (type I) and plantaris (type II) muscles in terms of ACE2 activity (17.35
      +/- 1.7 vs 15.09 +/- 0.8 uF.min(-1).mg(-1), respectively) and protein expression.
      ACE1 activity was higher in the plantaris muscle than in the soleus (71.5 +/- 3.9
      vs 57.9 +/- 1.1 uF.min(-1).mg(-1), respectively). Moreover, a comparative dose
      response curve of protein expression was established in the soleus and plantaris
      muscles, which indicated higher ACE1 levels in the plantaris muscle. The present
      findings showed similar ACE2 levels in the soleus and plantaris muscles that
      might result in a similar Ang II response; however, lower ACE1 levels could
      attenuate Ang II production and reduce bradykinin degradation in the soleus
      muscle compared to the plantaris. These effects should enhance the aerobic
      capacity necessary for oxidative muscle activity.

PMID- 20802976
TI  - Participation of endogenous opioids in the antinociception induced by resistance
      exercise in rats.
AB  - Exercise is a low-cost intervention that promotes health and contributes to the
      maintenance of the quality of life. The present study was designed to investigate
      the influence of different resistance exercise protocols on the nociceptive
      threshold of rats. Female Wistar rats were used to perform exercises in a weight
      lifting exercise model. The following groups were examined (N = 6 per group):
      untrained rats (control group); an acute protocol group consisting of rats
      submitted to 15 sets of 15 repetitions of resistance exercise (acute group); rats
      exercised with 3 sets of 10 repetitions, three times per week for 12 weeks
      (trained group), and a group consisting of trained rats that were further
      submitted to the acute protocol (trained-acute group). The nociceptive threshold
      was measured by the paw-withdrawal test, in which the withdrawal threshold
      (escape reaction) was measured by an apparatus applying force to the plantar
      surface of the animal paw. The opioid antagonist naloxone (2 mg/kg) was
      administered subcutaneously 10 min before the exercise protocols. The trained
      group demonstrated antinociception only up to day 45 of the 12-week training
      period. A significant increase (37%, P < 0.05) in the nociceptive threshold was
      produced immediately after exercise, decreasing to 15% after 15 min, when the
      acute exercise protocol was used. Naloxone reversed this effect. These data show
      that the acute resistance exercise protocol was effective in producing
      antinociception for 15 min. This antinociceptive effect is mediated by the
      activation of opioid receptors.

PMID- 20802977
TI  - Morphine infusions into the rostrolateral periaqueductal gray affect maternal
      behaviors.
AB  - It is well established that morphine inhibits maternal behaviors. Previous
      studies by our group have shown activation of the rostrolateral periaqueductal
      gray (rlPAG) upon inhibition-intended subcutaneous injections of morphine. In
      this context, we demonstrated that a single naloxone infusion into the rlPAG,
      following this opioid-induced inhibition, reactivated maternal behaviors. Since
      these data were obtained by using peripheral morphine injections, the present
      study was designed to test whether morphine injected directly into the rlPAG
      would affect maternal behaviors. Our hypothesis that morphine acting through the
      rlPAG would disrupt maternal behaviors was confirmed with a local infusion of
      morphine. The mothers showed shorter latency for locomotor behavior to explore
      the home cage (P = 0.049). Inhibition was especially evident regarding retrieving
      (P = 0.002), nest building (P = 0.05) and full maternal behavior (P = 0.023).
      These results support the view that opioidergic transmission plays a behaviorally
      meaningful inhibitory role in the rostrolateral PAG.

PMID- 20802978
TI  - Comparison of bone quantity by ultrasound measurements of phalanges between white
      and black children living in Parana, Brazil, with Europeans.
AB  - The objective of this study was to determine bone quantity by ultrasound
      measurements of the proximal finger phalanges (AD-SoS = amplitude-dependent speed
      of sound) of healthy Brazilian schoolchildren living in Parana, Brazil and to
      compare these values with European populations. The sample was composed of 1356
      Brazilian schoolchildren of both genders (660 males, 696 females), aged 6 to 11
      years, divided into white (840) and black (516) groups and compared to age- and
      gender-matched Europeans. AD-SoS of the schoolchildren increased significantly
      with age for both genders. Significantly higher AD-SoS values were observed for
      the white children (1916 +/- 58) compared to their black counterparts (1898 +/-
      72) and for the female gender (1920 +/- 61) compared to the male gender (1898 +/-
      66). Overall, the AD-SoS outcomes for females were similar to those of European
      studies. However, the AD-SoS of the Brazilian schoolchildren of both genders and
      skin colors was lower than that reported for children in Poland. AD-SoS outcomes
      for Brazilian schoolboys were similar to those obtained in Italian studies and
      were lower than those of the Spanish children. In conclusion, Brazilian
      schoolchildren of both genders and skin colors showed lower bone quantities than
      Polish children and Spanish males, and levels similar to Italian children and
      Spanish females.

PMID- 20802980
TI  - [Adolescent cannabis consumption and schizophrenia: epidemiological and
      experimental evidences].
AB  - Marijuana is consistently the most widely used illicit drug among teenagers and
      most users first experiment it in adolescence. Adolescence is a critical period
      between childhood and adulthood, including not only reproductive maturation, but
      also cognitive, emotional and social maturation. In this period adolescent brain
      is still in transition differing anatomically and neurochemically from the
      adult's one. The endocannabinoid system is an important determinant for cerebral
      maturation, therefore its strong stimulation by the delta-9-
      tetrahydrocannabinol, that acts through the endocannabinoid system, might lead to
      subtle but lasting neurobiological changes that can affect adult brain functions
      and behaviour. We summarize the more recent researches investigating the
      relationships between adolescent exposure to cannabinoids and increased risk for
      psychotic disease such as schizophrenia, as highlighted by both human and animal
      studies. Epidemiological evidence suggests that cannabis use is a risk factor for
      schizophrenia, and an exacerbation of symptoms and worsening of the schizophrenic
      prognosis may occur in individuals with a predisposition for schizophrenia. The
      characteristic of adolescent brain probably makes it more vulnerable to cannabis
      effect producing psychotic like symptoms and possibly cause schizophrenia.

PMID- 20802979
TI  - The repeatability and validity of questionnaires assessing occupational physical
      activity--a systematic review.
AB  - OBJECTIVES: This study aims to review systematically the repeatability and
      validity of questionnaires used to assess occupational physical activity among
      healthy adults. METHODS: We searched PubMed and Embase using occupational, work
      related, job-related, physical activity, motor activity, and questionnaires as
      keywords. Two reviewers independently performed article selection, data
      extraction, and quality assessment. The methodological quality and results of the
      studies were evaluated based on an existing checklist. The level of evidence and
      repeatability, criterion, and construct validity were rated. RESULTS: We included
      31 papers describing 30 questionnaires in the review. Repeatability was assessed
      in 22 studies, 11 used appropriate measures to assess 12 questionnaires. Intra
      class correlation coefficients and weighted Cohen's kappa ranged between 0.43
      0.95. Six studies used appropriate measures to assess criterion validity of 13
      questionnaires. One questionnaire, the Tecumseh Self Administered Occupational
      Physical Activity Questionnaire (TOQ), showed good criterion validity against a
      physical activity (PA) record. Eighteen studies used appropriate measures to
      assess the construct validity of 23 questionnaires. Comparison included those
      against accelerometers, maximal oxygen uptake, questionnaires, and body
      composition measures. None showed good construct validity. CONCLUSIONS: There is
      strong evidence for good reliability of four questionnaires. None of the reviewed
      questionnaires showed good criterion validity compared to objective measures.
      Compared to PA records, moderate-to-good validity was observed for two
      questionnaires. Objective measures of occupational PA are needed.

PMID- 20802981
TI  - [Assessing coping strategies in alcoholics: Comparison while controlling for
      personality disorders, cognitive impairment and benzodiazepine misuse].
AB  - INTRODUCTION: Better coping skills are related to greater capacity for dealing
      with stressful situations. This relationship could be relevant for the prevention
      of alcohol-misuse relapse. Relapse rate is higher among severe alcoholics. The
      current study examines whether this may be due to a lack of coping skills in
      those cases. The COPE (Coping Orientations to Problems Experienced) is a
      questionnaire used for assessing coping strategies. METHOD: COPE scores of 216
      alcohol inpatients are compared while controlling for personality disorders
      (PDs), cognitive impairment (CI) and benzodiazepine misuse (BM). RESULTS:
      Patients with PDs score higher on the scales of Humor, Venting emotions,
      Substance use and Use of instrumental support. However, there are no differences
      in COPE scores attributable to CI or BM. CONCLUSIONS: Alcoholics with Personality
      disorders use maladaptive coping strategies. Patients presenting CI or BM have
      low capacity for introspection and are unable to properly evaluate their own
      abilities, so that they tend to give a socially favorable but unrealistic image
      of themselves. Longitudinal studies are needed to evaluate the predictive
      validity of the coping skills before training alcoholics, who are especially
      difficult to assess due to their lower capacity for objective self-observation.

PMID- 20802982
TI  - [Validation of the Psychiatric Diagnostic Screening Questionnaire (PDSQ) in a
      Spanish sample of alcoholic patients].
AB  - OBJECTIVE: This study evaluates the psychometric properties of the Psychiatric
      Diagnostic Screening Questionnaire (PDSQ) in alcohol-dependent Spanish population
      as a means of detecting psychiatric comorbidity. METHODS: The PDSQ (Zimmerman,
      2001) is a self-administered questionnaire with 125 items which can be applied in
      just 15 minutes, enabling rapid and effective screening of the psychiatric
      disorders (Axis I) most commonly found among substance abusers. After linguistic
      adaptation (translation/back-translation) and verification of its content
      validity, the PDSQ was administered to 156 alcohol-dependent patients (DSM-IV
      criteria; women = 36%), treated consecutively in an alcohol-disorders treatment
      setting. Its psychometric properties (reliability and validity) were determined,
      applying the DSM-IV criteria as a "gold standard", by means of SCID interview.
      RESULTS: Using the original cut-off points, the PDSQ showed excellent internal
      reliability (Alfa = 0.68-0.96) and diagnostic validity, with mean sensitivity =
      99.6% (range: 96.6%-100%), specificity = 69.5% (range: 51.9%- 94.6%) and NPV =
      99.8% (range: 98.6%-100%). Diagnostic efficiency with the original cut-off points
      was 73.2%, rising to 91.6% using new cut-off points for certain scales, with a
      degree of agreement with DSM-IV criteria of Kappa = .303 -. 896. CONCLUSIONS: The
      PDSQ is a reliable and valid instrument for detecting psychiatric comorbidity in
      alcoholic individuals. Its psychometric properties and the added value of self
      administration and short application time make it a recommended instrument for
      use in routine clinical settings.

PMID- 20802983
TI  - [Opportunities for the improvement of the methadone service in primary health
      care, from the professionals' point of view].
AB  - OBJECTIVE: To identify and prioritize improvement opportunities, according to the
      European Foundation for Quality Management model (EFQM) model, of the methadone
      dispensing service in Andalusian Primary Health Care, from the point of view of
      professionals. METHOD: Delphi consensus method, implemented from September 2007
      to March 2008 by means of three rounds of interviews with questionnaires
      administered by electronic mail to 39 professionals. The Panel of experts was
      made up of Dispensers and Prescribers of methadone as well as Coordinators of
      welfare services from the Methadone Treatment Program (MTP). Selection criteria
      were: Being in active employment with a minimum of 3 years experience. Sample
      diversification variables: Professional role, geographical environment and type
      of habitat. Recruitment: By means of key professional bodies from different
      institutions. RESULTS: 48 improvement opportunities were identified. Thirteen of
      these obtained a high level of agreement in the final round. According to the
      EFQM model, the dimensions that obtained the most consensus in relation to
      improving the care service were: Leadership, Alliances and Resources. The
      dimension that caused the greatest disagreement was Processes. CONCLUSIONS: In
      spite of its having been implemented since 1997 in Andalusian Primary Health
      Care, the methadone dispensing service is at an implementation phase, rather than
      what could be classed as a fully deployed stage.

PMID- 20802984
TI  - [Process evaluation of the school-based cannabis use prevention program
      "xkpts.com" in adolescents from Barcelona in 2006].
AB  - BACKGROUND: The observed positive effects of school-based prevention programs are
      frequently lower than what was expected, usually due to inadequate
      implementation. AIMS: To describe the process evaluation of a cannabis use school
      based prevention program (xkpts.com), to measure teachers' satisfaction with the
      program and to define quantitative and qualitative parameters for assessing the
      exhaustiveness of the intervention. METHODS: Cross-sectional descriptive study.
      SAMPLE: 117 9th-grade classes in 39 schools (2812 students). The information was
      gathered by means of a self-report questionnaire for teachers and families. A
      descriptive analysis was made of the implementation of the intervention in the
      classrooms and of the families' participation. RESULTS: Teachers' response rate
      was 65%. Discussion was the method most widely applied (100% of the classrooms)
      and DVD was the most widely used material (93.4%). Skills training was applied in
      72.4% of the classrooms. In 59.2% of the classrooms there was an acceptable
      intervention (at least 8 of the 16 preventive activities), while in 38.2% there
      was a qualified intervention (at least 1 activity for each general lesson and 2
      for each specific one). Mean score given to the program by teachers was 7.4, and
      81.6% of them reported their intention to apply it again. Participation rate of
      the students' families was 28.3% (796). CONCLUSIONS: The intervention was
      acceptable in two out of three classrooms, while in four out of ten the protocol
      was applied strictly. Greater participation of the students' families
      corresponded to those schools in which the intervention was better implemented.

PMID- 20802985
TI  - [Cocaine base paste: experience from the Montevideo Poison Control Center].
AB  - BACKGROUND: In Uruguay, cocaine base paste (CBP, pasta base) is a widely used
      form of cocaine. The aim of our study is to determine the main clinical
      characteristics of CBP abusers. METHODS: Retrospective, single-center study of
      consultations at the Montevideo Poison Control Center between January 1, 2004 and
      December 31, 2005. RESULTS: One hundred and thirteen consultations were included,
      with an average age of 22 years (+ - 0.5 years) and a female-male sex ratio of
      1:4.3. The consultations were related to drug overdose (77%), suicide attempt
      (16.8%), and wanting to give up CBP use (6.2%). In 48.1% the time elapsed since
      inhalation of CBP was less than 6 hours. Doses varied between 0.5 gr. and 25 gr.
      Use of other drugs at the same time, such as alcohol, marijuana or
      benzodiazepines, was common (51 cases). The symptoms most frequently observed
      were neuropsychiatric and cardiovascular, followed by respiratory symptoms. In
      16.8% of patients, reason for the consultation was intentional acute ingestion of
      drugs, considered as a suicide attempt, occurring within a few hours of drug
      consumption. DISCUSSION: CBP users are mostly young males. Although clinical
      findings are compatible with those for cocaine abuse, euphoria is a major
      clinical feature in CBP abusers. The presence of respiratory symptoms reflects
      the complications associated with the ingestion route. Suicide attempts occurring
      within a few hours of CBP confirm the high prevalence of suicidal ideation
      reported by other authors. cocaine base paste, clinical features, suicide
      attempts.

PMID- 20802986
TI  - [Personality and frontal symptomatology in addicts and nonclinical population:
      toward a neuropsychology of personality].
AB  - OBJECTIVE: For many years now, Neuropsychology and the Psychology of Personality
      have developed in parallel, without any attempt to integrate the knowledge
      provided by the two disciplines. This paper sets out to analyze the relationship
      between the presence of symptoms in daily life related to the functioning of the
      brain's frontal lobes and individuals' personality patterns. PARTICIPANTS AND
      METHODS: The Dysexecutive Questionnaire (DEX-Sp), the Frontal System Behavior
      Scale (FrSBe- Sp) and the Inventory of Temperament and Character Revised (TCI-R)
      were administered to 421 non-clinical participants and 246 individuals in
      treatment for substance abuse or dependence. RESULTS: Significant correlations
      were found between symptoms for all frontal syndromes (mesial, dorsolateral and
      orbital) and some personality traits (novelty seeking, harm avoidance and self
      directedness), even more than 50% of the variance being predicted. DISCUSSION AND
      CONCLUSIONS: Results suggest that frontal performance should be seen as a
      continuous dimensional variable, ranging from optimal to non-adaptive
      performance, without a neat cut-off point. Addiction would be related to an
      increase in frontal symptoms, both mesial (apathy) and orbital (disinhibition),
      as well as dorsolateral (dysexecutive syndrome), and this would result in changes
      in the previous personality pattern. These data seriously question the supposed
      genetic basis of temperamental traits, and suggest hypotheses of great relevance
      for clinicians.

PMID- 20802987
TI  - [Psychopathological symptoms and personality traits in young adult cannabis
      dependent treatment seekers: A comparative study].
AB  - The aim of this paper was to describe the psychopathological and personality
      profile associated with cannabis dependence in young adults and to compare it
      with those of non-addictive disorders and the normal population. The sample
      consisted of 141 cannabis-dependent subjects attending a psychiatric outpatient
      clinic, 140 psychiatric patients with non-addictive disorders and 140 subjects
      from the general population chosen to match the patient samples for age, gender
      and socioeconomic level. All participants were assessed with different
      instruments related to personality (Impulsiveness Scale, Sensation-Seeking Scale
      and STAI) and psychopathology (SCL-90-R, BDI, STAI and Inadaptation Scale).
      Patients from the clinical groups presented more anxiety and depression symptoms
      than healthy participants, and had more problems adjusting to everyday life, but
      there were no differences between the two clinical groups. Cannabis-dependent
      patients were specifically characterized by low educational level and by the
      presence of paranoid ideation; they were also more impulsive and sensation
      seeking than those from the other two groups. We discuss the implications of this
      study for clinical practice and for further research.

PMID- 20802988
TI  - [An approach to the assessment of the effectiveness of a drug use prevention
      program in secondary education in Andalusia].
AB  - This article examines the analysis of drug use among Secondary Education students
      in Andalusia from two different studies: the Health Behavior in School-aged
      Children Study (HBSC), in its 2006 edition, and a study assessing the
      implementation of the Prevenir para Vivir ("Prevent to Live") drug use prevention
      program in the education field. To this end, on the one hand the paper analyzes
      the use of tobacco, alcohol and cannabis among Andalusian adolescents on the HBSC
      Study, and on the other, selects two groups of adolescents to examine and compare
      their drug use: a group from the HBSC Study who had not participated in any drug
      use prevention program and in whose schools the staff had not received training
      in relation to these issues (called HBSC Control Group), and a group of
      adolescents who had participated in the Prevenir para Vivir drug use prevention
      program working with specialized staff (called Prevenir para Vivir Experimental
      Group). The results indicate, first, higher levels of drug use in older students
      than in younger ones; and, second, on comparing the two groups, that adolescents
      who have received drug prevention programs with specialized staff are not always
      those most likely to present healthier drug use. These results must therefore be
      interpreted as offering only limited support to drug use prevention programs.

PMID- 20802989
TI  - [Longitudinal research on treated alcoholism: Systematic review of long-term
      follow-ups].
AB  - AIMS: To analyze the methodological design of long-term longitudinal studies of
      alcoholics who have undergone treatment. METHODS: Systematic review of
      prospective longitudinal studies of treated alcoholics with follow-up periods of
      at least 8 years, and published in English, during the period 1983-2009. The
      review includes 9 studies which analyzed: follow-up evaluations, information
      sources, the period of reference in the final assessment, the measurement of
      alcohol use, the operationalization of drinking patterns, and data analysis.
      RESULTS: 2434 patients (ranging between 57 and 850 per study) were studied on
      average for a period of 15.3 (D.T. = 3.2) years (range 8-20 years). Studies
      differ in the number of intermediate evaluations (0, 1, 3, 4) and the length of
      the period considered for the final evaluation (the whole period, the last 3
      years, the last year, last 6 months, last month or present situation). Drinking
      patterns tend to be used as the main outcome variable, but they are
      operationalized in non-equivalent forms and the analysis is performed using
      classical cross-sectional statistical techniques. Alcoholism evolution is studied
      by analyzing the evolution of drinking patterns and patients' life situation
      during the period under study. CONCLUSIONS: The scarce amount of data available
      on the evolution of treated alcoholism cannot be compared across studies due to
      considerable methodological differences. There is a need to promote common
      methodological criteria in relation to follow-up strategies. New statistical
      methods that permit longitudinal analysis for non-balanced and correlated data
      should also be incorporated.

PMID- 20802990
TI  - [Anticoagulation in the elderly].
AB  - The recommendations for anticoagulation in over 80 years old patients are based
      on the thromboembolic/bleeding risk relation. They add to the published
      recommendations for the specific indications. Low-molecular-weight heparin (LMWH)
      is used to prevent thromboembolism postoperatively. Compression stockings and/or
      intermittent pneumatic compression are used if bleeding risk is very high. The
      dose is increased starting at day two if the thromboembolic risk is very high.
      Bleeding and thromboembolic risks are re-evaluted daily. The antithrombotic
      therapy is adjusted accordingly. Prophylaxis of thromboembolism in patients with
      acute illnesses and bedrest is performed according postoperative care. Two-thirds
      of therapeutic doses of low-molecular-weight heparin are used to treat acute
      venous thromboembolism. Reduced renal function (creatinine clearance <30 ml/ min
      for most LMWHs or <20 ml/min for tinzaparin) should result in a further reduction
      of dose. Intensity and duration of prophylaxis of recurrent events with vitamin K
      antagonist or LMWH in malignancy follow current or herein described
      recommendations. Patients with atrial fibrillation are treated with vitamin K
      antagonists adjusted to an INR of 2-3 for prophylaxis of embolism. Further
      details of anticoagulant therapy should be in agreement with the national or
      international recommendations.

PMID- 20802991
TI  - A novel melanoma-targeting peptide screened by phage display exhibits antitumor
      activity.
AB  - Peptide display on the phage surface has been widely used to identify specific
      peptides targeting several in vivo and in vitro tumor cells and the tumor
      vasculature, playing a role in the discovery of bioactive antitumor agents.
      Bioactive peptides have been selected to target important tumor receptors or
      apoptosis-associated molecules such as p53. Presently, we attempted to identify
      potentially antitumor bioactive molecules using the whole cell surface as the
      recognizable static matrix. Such methodology could be advantageous in cancer
      therapy because it does not require previous characterization of target
      molecules. Using a C7C phage display library, we screened for peptides binding to
      the B16F10-Nex2 melanoma cell surface after pre-absorption on melan-A lineage.
      After a few rounds of enrichment, 50 phages were randomly selected, amplified,
      and tested for inhibition of tumor cell proliferation. Seven were active, and the
      corresponding peptide of each phage was chemically synthesized in the cyclic form
      and tested in vitro. Three peptides were able to preferentially inhibit the
      melanoma lineage. A unique peptide, [-CSSRTMHHC-], exhibited in vivo antitumor
      inhibitory activity against a subcutaneous melanoma challenge, rendering 60% of
      mice without tumor growth. Further, this peptide also markedly inhibited in vitro
      and in vivo the tumor cell invasion and cell-to-cell adhesiveness in vitro. This
      is the first report on a bioactive peptide derived from a C7C library active
      against whole melanoma cells in vitro and in vivo.

PMID- 20802992
TI  - [Evidence-based therapy of depression: S3 guidelines on unipolar depression].
AB  - Unipolar depressive disorders are among the most frequent reasons for utilizing
      the health care system. Although efficacious treatments are available and further
      advances have recently been made there is still a need for improving diagnostic
      and therapeutic procedures. Alignment of treatment on evidence-based treatment
      guidelines establishes an essential mainstay. The new S3 and National Health Care
      guidelines on unipolar depression, the compilation of which was coordinated by
      the German Society of Psychiatry, Psychotherapy and Neurology (DGPPN) and which
      were approved by 29 scientific and professional associations, is the ambitious
      effort to present state of the art evidence and clinical consensus for the
      treatment of depression. For pharmacotherapy of depression differentiated
      recommendations can be given, also separate from and in addition to
      psychotherapy.

PMID- 20802993
TI  - [Sonography of the parenchyma in Parkinson's disease].
AB  - Transcranial sonography (TCS) of the brain parenchyma is a non-invasive and
      easily applicable neuroimaging technique which is used as a diagnostic tool in
      Parkinson's disease. Up to 90% of patients with idiopathic Parkinson's disease
      but only 10-15% of the healthy population show an abnormal echogenicity
      (hyperechogenicity) of the substantia nigra (SN). TCS has been demonstrated to be
      a useful tool in the differential diagnosis of patients with essential tremor or
      atypical parkinsonian syndromes, including the parkinsonian variant of multiple
      system atrophy (MSA-P) and progressive supranuclear palsy (PSP) where
      hyperechogenicity of the SN is less frequent. Abnormal echogenicity of the SN has
      been found in almost all investigated monogenic types of parkinsonism and even in
      asymptomatic mutation carriers. The nature of the pathological substrate leading
      to the abnormal echogenicity of the SN remains elusive. Longitudinal studies of
      asymptomatic subjects with abnormal echogenicity of the SN are still ongoing to
      evaluate the risk for developing Parkinson's disease in the future in these
      subjects.

PMID- 20802994
TI  - PCL balancing, an example of the need to couple detailed biomechanical parameters
      with clinical functional outcome.

PMID- 20802995
TI  - Changes in articular cartilage after meniscectomy and meniscus replacement using
      a biodegradable porous polymer implant.
AB  - PURPOSE: To evaluate the long-term effects of implantation of a biodegradable
      polymer meniscus implant on articular cartilage degeneration and compare this to
      articular cartilage degeneration after meniscectomy. METHODS: Porous polymer
      polycaprolacton-based polyurethane meniscus implants were implanted for 6 or 24
      months in the lateral compartment of Beagle dog knees. Contralateral knees were
      meniscectomized, or left intact and served as controls. Articular cartilage
      degeneration was evaluated in detail using India ink staining, routine histology,
      immunochemistry for denatured (Col2-3/4M) and cleaved (Col2-3/4C(short)) type II
      collagen, Mankin's grading system, and cartilage thickness measurements. RESULTS:
      Histologically, fibrillation and substantial immunohistochemical staining for
      both denatured and cleaved type II collagen were found in all three treatment
      groups. The cartilage of the three groups showed identical degradation patterns.
      In the 24 months implant group, degradation appeared to be more severe when
      compared to the 6 months implant group and meniscectomy group. Significantly more
      cartilage damage (India ink staining, Mankin's grading system, and cartilage
      thickness measurements) was found in the 24 months implant group compared to the
      6 months implant group and meniscectomy group. CONCLUSION: Degradation of the
      cartilage matrix was the result of both mechanical overloading as well as
      localized cell-mediated degradation. The degeneration patterns were highly
      variable between animals. Clinical application of a porous polymer implant for
      total meniscus replacement is not supported by this study.

PMID- 20802996
TI  - Gout and coexisting pseudogout in the knee joint.
AB  - PURPOSE: We report the unusual case of a 63-year-old man with gout and coexisting
      pseudogout (calcium pyrophosphate dihydrate crystal deposition disease) affecting
      the same joint. In this report, we describe the clinical features of the patient
      in addition to the characteristics of the crystals extracted from his affected
      joint, examined using compensated polarized microscopy. METHODS: Synovial fluid
      and specimens of the lateral meniscus of the patient's knee joint taken during
      arthroscopy were analyzed using compensated polarized microscopy to evaluate the
      presence and type of crystals. RESULTS: Compensated polarized microscopy revealed
      both monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals
      extracted from the knee joint. CONCLUSIONS: Our findings suggest that the
      coexistence of gout and pseudogout should be considered in the diagnosis of
      crystal-induced arthritis. Careful crystal evaluation using compensated polarized
      microscopy may reveal similar cases with MSU and CPPD crystals in the same joint.

PMID- 20802997
TI  - More on ADORA.

PMID- 20802999
TI  - Information processing deficits and nitric oxide signalling in the phencyclidine
      model of schizophrenia.
AB  - RATIONALE: Schizophrenia-like cognitive deficits induced by phencyclidine (PCP),
      a drug commonly used to model schizophrenia in experimental animals, are
      attenuated by nitric oxide (NO) synthase inhibitors. Furthermore, PCP increases
      NO levels and sGC/cGMP signalling in the prefrontal cortex in rodents. Hence, a
      cortical NO/sGC/cGMP signalling pathway may constitute a target for novel
      pharmacological therapies in schizophrenia. OBJECTIVES: The objective of this
      study was to further investigate the role of NO signalling for a PCP-induced
      deficit in pre-attentive information processing. MATERIALS AND METHODS: Male
      Sprague-Dawley rats were surgically implanted with NO-selective amperometric
      microsensors aimed at the prefrontal cortex, ventral hippocampus or nucleus
      accumbens, and NO levels and prepulse inhibition (PPI) were simultaneously
      assessed. RESULTS: PCP treatment increased NO levels in the prefrontal cortex and
      ventral hippocampus, but not in the nucleus accumbens. The increase in NO levels
      was not temporally correlated to the deficit in PPI induced by PCP. Furthermore,
      pretreatment with the neuronal NO synthase inhibitor N-propyl-L-arginine dose
      dependently attenuated both the increase in prefrontal cortex NO levels and the
      deficit in PPI. CONCLUSIONS: These findings support a demonstrated role of NO in
      the behavioural and neurochemical effects of PCP. Furthermore, this effect is
      brain region-specific and mainly involves the neuronal isoform of NOS. However, a
      temporal correlation between a PCP-induced disruption of PPI and an increase in
      prefrontal cortex NO levels was not demonstrated, suggesting that the interaction
      between PCP and the NO system is more complex than previously thought.

PMID- 20803000
TI  - Differential effects of post-weaning juvenile stress on the behaviour of C57BL/6
      mice in adolescence and adulthood.
AB  - RATIONALE: There is evidence that events early in post-weaning life influence
      brain development and subsequent adult behaviour and therefore play an important
      role in the causation of certain psychiatric disorders in later life. Exposing
      rodents to stressors during the juvenile period has been suggested as a model of
      induced predisposition for these disorders. OBJECTIVE: This is the first study to
      examine behavioural and pharmacological changes in adolescence and adulthood
      following juvenile stress in mice. MATERIALS AND METHODS: Two cohorts of mice
      were simultaneously exposed to a stress protocol during postnatal days (PND) 25
      30. Behavioural assessments reflecting emotional functions, cognitive functions,
      and psychostimulant sensitivity were then carried out at two time points: one
      cohort was tested during adolescence (PND 39-54; adolescent group), and the
      second cohort was tested during adulthood (PND 81-138; adult group). RESULTS: In
      the adolescent mice, juvenile stress significantly attenuated conditioned
      freezing and led to decreased anxiety-like behaviour in the elevated plus maze,
      whereas no effect was observed on these tests in the adult mice. In contrast,
      adult mice exhibited poor avoidance learning following juvenile stress. When
      tested during adulthood, the mice stressed during the juvenile period showed a
      sensitised response to amphetamine compared to controls, whereas the response
      during adolescence was similar in stressed and control animals. CONCLUSIONS: Our
      results suggest that exposure to stressors during the juvenile period can exert
      long-term effects on the brain and behaviour and that these effects differ
      depending on whether the animals are tested during adolescence or adulthood.

PMID- 20802998
TI  - Biological aspect of hyperthymic temperament: light, sleep, and serotonin.
AB  - RATIONALE: Hyperthymic temperament is one of several premorbid temperaments
      putatively associated with bipolar disorder. Several reports suggest that
      depressive patients with hyperthymic temperament may belong to the proposed soft
      bipolar spectrum. OBJECTIVES: To investigate biological aspects of hyperthymic
      temperament, the present study examined daily activity, sleep time, central
      serotonergic function, and other relevant variables in relation to hyperthymic
      temperament in healthy subjects. METHODS: Fifty six healthy subjects were
      monitored via the actigraphy system to measure daily total activity, sleep time,
      and illuminance. A neuroendocrine challenge test was performed to estimate
      central serotonergic function. RESULTS: Multiple regression analysis revealed
      that higher illuminance of daytime, greater fluctuation in sleep time, and lower
      central serotonergic function significantly and independently predicted
      hyperthymic temperament scores. CONCLUSIONS: The present findings suggest that
      light, sleep, and serotonin are crucial factors in understanding hyperthymic
      temperament, which may be common to bipolar disorder.

PMID- 20803001
TI  - Short- and long-term anxiogenic effects induced by a single injection of
      subconvulsant doses of pilocarpine in rats: investigation of the putative role of
      hippocampal pathways.
AB  - RATIONALE: Behavioral consequences of convulsive episodes are well documented,
      but less attention was paid to changes that occur in response to subconvulsant
      doses of drugs. OBJECTIVES: We investigated short- and long-term effects of a
      single systemic injection of a subconvulsant dose of pilocarpine on the behavior
      of rats as evaluated in the elevated plus maze. METHODS AND RESULTS: Pilocarpine
      induced an anxiogenic-like profile 24 h later, and this effect persisted for up
      to 3 months (% of time spent on open arms at 24 h, control = 35.47 +/- 3.23;
      pilocarpine 150 = 8.2 +/- 2.6; 3 months, control = 31.9 +/- 5.5; pilocarpine 150
      = 9.3 +/- 4.9). Temporary inactivation of fimbria-fornix with lidocaine 4%
      promoted an anxiolytic-like effect per se, suggesting a tonic control of this
      pathway on the modulation of anxiety-related behaviors. Lidocaine also reduced
      the anxiogenic-like profile of animals tested 1 month after pilocarpine treatment
      (% of time spent on open arms, saline + phosphate-buffered saline (PBS) = 31.7 +
      3.7; saline + lidocaine = 54.4 + 4.7; pilocarpine + PBS = 10.3 + 4.1; pilocarpine
      + lidocaine = 40.1 + 9.1). To determine whether the anxiogenic-like effect was
      mediated by septal region or by direct hippocampal projections to the
      diencephalon, the neural transmission of post-commissural fornix was blocked, and
      a similar reduction in the anxiogenic-like effect of pilocarpine was observed.
      CONCLUSIONS: Our findings suggest that a single systemic injection of pilocarpine
      may induce long-lasting anxiogenic-like behavior in rats, an effect that appears
      to be mediated, in part, through a direct path from hippocampus to medial
      hypothalamic sites involved in fear responses.

PMID- 20803003
TI  - Influence of second virial coefficient and persistence length on dilute solution
      polymer conformation.
AB  - The effect of different types of short- and long-range intrachain interactions
      along the polymeric backbone on the persistence length of a polymer, as well as
      on other properties such as solvation (characterized by the second virial
      coefficient), dilute solution conformation, specific refractive index increment,
      and intrinsic viscosity, were studied using multi-detector size-exclusion
      chromatography and off-line techniques. The polymers in this study, namely,
      polystyrene (PS), poly(vinyl chloride) (PVC), and poly(p-vinylbenzyl chloride)
      (PpVBC), were chosen based on intrachain interactions specific to each,
      intrachain repulsion in PVC, attraction in PS, and hindered attraction in PpVBC,
      and also based on a coincidence in molar mass averages and distributions between
      the polymers. The latter allowed polymeric properties of the three polymers to be
      compared to each other at the same molar mass and/or degree of polymerization.
      From the comparisons emerged the effects of intrachain repulsion between
      consecutive monomers and of the second virial coefficient on chain stiffness and
      solvation. The increase in the second virial coefficient corresponded to an
      increase in both polymer solvation and rigidity, while increased intrachain
      repulsion between consecutive monomers increased polymer solvation while
      decreasing chain rigidity.

PMID- 20803002
TI  - Quantification of neurotransmitter amino acids by capillary electrophoresis laser
      induced fluorescence detection in biological fluids.
AB  - The role of neurotransmitter amino acids (NAAs) in the functioning of the nervous
      system has been the focus of increasingly intense research over the past several
      years. Among the various amino acids that have important roles as
      neurotransmitters, there are alanine (Ala), glutamic acid (Glu), aspartic acid
      (Asp), serine (Ser), taurine (Tau) and glycine (Gly). NAAs are present in plasma,
      cells and--at trace levels--in all biological fluids, but complex components in
      biological matrices make it difficult to determine them in biological samples. We
      describe a new capillary electrophoresis (CE) method with laser-induced
      fluorescence detection by which analytes are resolved in less than 12 minutes in
      a 18 mmol/L phosphate run buffer at pH 11.6. The use of elevated temperatures
      during sample derivatization leads to a drastic reduction in the reaction time,
      down to 20 min, compared to the 6-14 h usually described for reactions between
      FITC and amino acids at room temperature. In order to demonstrate its wide range
      of applications, the method was applied to the analysis of NAA in human plasma
      and in other sample types, such as red blood cells, urine, cultured cells,
      cerebrospinal fluid, saliva and vitreous humor, thus avoiding the typical
      limitations of other methods, which are normally suitable for use with only one
      or two matrix types.

PMID- 20803004
TI  - Proton transfer reaction mass spectrometry for the sensitive and rapid real-time
      detection of solid high explosives in air and water.
AB  - Relying on recent developments in proton transfer reaction mass spectrometry (PTR
      MS), we demonstrate here the capability of detecting solid explosives in air and
      in water in real time. Two different proton transfer reaction mass spectrometers
      have been used in this study. One is the PTR-TOF 8000, which has an enhanced mass
      resolution (m/Deltam up to 8,000) and high sensitivity (~50 cps/ppbv). The second
      is the high-sensitivity PTR-MS, which has an improved limit of detection of about
      several hundreds of parts per quadrillion by volume and is coupled with a direct
      aqueous injection device. These instruments have been successfully used to
      identify and monitor the solid explosive 2,4,6-trinitrotoluene (TNT) by analysing
      on the one hand the headspace above small quantities of samples at room
      temperature and from trace quantities not visible to the naked eye placed on
      surfaces (also demonstrating the usefulness of a simple pre-concentration and
      thermal desorption technique) and by analysing on the other hand trace compounds
      in water down to a level of about 100 pptw. The ability to identify even minute
      amounts of threat compounds, such as explosives, particularly within a complex
      chemical environment, is vital to the fight against crime and terrorism and is of
      paramount importance for the appraisal of the fate and harmful effects of TNT at
      marine ammunition dumping sites and the detection of buried antipersonnel and
      antitank landmines.

PMID- 20803005
TI  - Low-temperature co-fired ceramic microchannels with individually addressable
      screen-printed gold electrodes on four walls for self-contained electrochemical
      immunoassays.
AB  - Microchannel devices were constructed from low-temperature co-fired ceramic
      (LTCC) materials with screen-printed gold (SPG) electrodes in three dimensions-
      on all four walls--for self-contained enzyme-linked immunosorbant assays with
      electrochemical detection. The microchannel confines the solution to a small
      volume, allowing concentration of electroactive enzymatically generated product
      and nearby electrodes provide high-speed and high-sensitivity detection: it also
      facilitates future integration with microfluidics. LTCC materials allow easy
      construction of three-dimensional structures compared with more traditional
      materials such as glass and polymer materials. Parallel processing of LTCC layers
      is more amenable to mass production and fast prototyping, compared with
      sequential processing for integrating multiple features into a single device.
      LTCC and SPG have not been reported previously as the basis for microchannel
      immunoassays, nor with integrated, individually addressable electrodes in three
      dimensions. A demonstration assay for mouse IgG at 5.0 ng/mL (3.3 * 10(-11) M)
      with electrochemical detection was achieved within a 1.8 cm long * 290 MUm high *
      130 MUm wide microchannel (approximately 680 nL). Two of four SPG electrodes span
      the top and bottom walls and serve as the auxiliary electrode and the assay site,
      respectively. The other two (0.7 cm long * 97 MUm wide) are centered lengthwise
      on the sidewalls of the channel. One serves as the working and the other as the
      pseudoreference electrode. The immunoassay components were immobilized at the
      bottom SPG region. Enzymatically generated p-aminophenol was detected at the
      internal working electrode within 15 s of introducing the enzyme substrate p
      aminophenyl phosphate. A series of buffer rinses avoided nonspecific adsorption
      and false-positive signals.

PMID- 20803006
TI  - Modeling the relative impact of capsular tissue effects on implanted glucose
      sensor time lag and signal attenuation.
AB  - Little is known mechanistically about why implanted glucose sensors lag behind
      blood glucose levels in both the time to peak sensor response and the magnitude
      of peak sensor response. A mathematical model of glucose transport from
      capillaries through surrounding tissue to the sensor surface was constructed to
      address how different aspects of the tissue affect glucose transport to an
      implanted sensor. Physiologically relevant values of capsule diffusion
      coefficient, capsule porosity, cellular glucose consumption, capsule thickness,
      and subcutaneous vessel density were used as inputs to create simulated sensor
      traces that mimic experimental instances of time lag and concentration
      attenuation relative to a given blood glucose profile. Using logarithmic
      sensitivity analysis, each parameter was analyzed to study the effect of these
      variables on both lag and attenuation. Results identify capsule thickness as the
      strongest determinant of sensor time lag, while subcutaneous vessel density and
      capsule porosity had the largest effects on attenuation of glucose that reaches
      the sensor surface. These findings provide mechanistic insight for the rational
      design of sensor modifications that may alleviate the deleterious consequences of
      tissue effects on implanted sensor performance.

PMID- 20803008
TI  - Abstracts of the XXXII Congress of the Spanish Society of Pharmacology. May 12
      14, 2010. Barcelona, Spain.

PMID- 20803007
TI  - Optimization of parameters for coverage of low molecular weight proteins.
AB  - Proteins with molecular weights of <25 kDa are involved in major biological
      processes such as ribosome formation, stress adaption (e.g., temperature
      reduction) and cell cycle control. Despite their importance, the coverage of
      smaller proteins in standard proteome studies is rather sparse. Here we
      investigated biochemical and mass spectrometric parameters that influence
      coverage and validity of identification. The underrepresentation of low molecular
      weight (LMW) proteins may be attributed to the low numbers of proteolytic
      peptides formed by tryptic digestion as well as their tendency to be lost in
      protein separation and concentration/desalting procedures. In a systematic
      investigation of the LMW proteome of Escherichia coli, a total of 455 LMW
      proteins (27% of the 1672 listed in the SwissProt protein database) were
      identified, corresponding to a coverage of 62% of the known cytosolic LMW
      proteins. Of these proteins, 93 had not yet been functionally classified, and
      five had not previously been confirmed at the protein level. In this study, the
      influences of protein extraction (either urea or TFA), proteolytic digestion
      (solely, and the combined usage of trypsin and AspN as endoproteases) and protein
      separation (gel- or non-gel-based) were investigated. Compared to the standard
      procedure based solely on the use of urea lysis buffer, in-gel separation and
      tryptic digestion, the complementary use of TFA for extraction or endoprotease
      AspN for proteolysis permits the identification of an extra 72 (32%) and 51
      proteins (23%), respectively. Regarding mass spectrometry analysis with an LTQ
      Orbitrap mass spectrometer, collision-induced fragmentation (CID and HCD) and
      electron transfer dissociation using the linear ion trap (IT) or the Orbitrap as
      the analyzer were compared. IT-CID was found to yield the best identification
      rate, whereas IT-ETD provided almost comparable results in terms of LMW proteome
      coverage. The high overlap between the proteins identified with IT-CID and IT-ETD
      allowed the validation of 75% of the identified proteins using this orthogonal
      fragmentation technique. Furthermore, a new approach to evaluating and improving
      the completeness of protein databases that utilizes the program RNAcode was
      introduced and examined.

PMID- 20803010
TI  - "Tumor immunology meets oncology (TIMO) VI" from 7th to 8th of May 2010 in Halle,
      Germany.

PMID- 20803009
TI  - Successful pericardio-amniotic shunting for fetal intrapericardial teratoma.

PMID- 20803011
TI  - Immunization with a recombinant GnRH vaccine fused to heat shock protein 65
      inhibits mammary tumor growth in vivo.
AB  - Gonadotrophin-releasing hormone (GnRH) is the prime decapeptide hormone in the
      regulation of mammalian reproduction. Active immunization against GnRH has been a
      good treatment option to fight against hormone-dependent disease such as breast
      cancer. We designed and purified a novel protein vaccine Hsp65-GnRH(6) containing
      heat shock protein 65 (Hsp65) and six copies of GnRH in linear alignment.
      Immunization with Hsp65-GnRH(6) evoked strong humoral response in female mice.
      The generation of specific anti-GnRH antibodies was detected by ELISA and
      verified by western blot. In addition, anti-GnRH antibodies effectively
      neutralized endogenous GnRH activity in vivo, as demonstrated by the degeneration
      of the ovaries and uteri in the vaccinated mice. Moreover, the growth of EMT-6
      mammary tumor allografts was inhibited by anti-GnRH antibodies. Histological
      examinations have shown that there was increased focal necrosis in tumors. Taken
      together, our results showed that immunization with Hsp65-GnRH(6) elicited high
      titer of specific anti-GnRH antibodies and further led to atrophy of reproductive
      organs. The specific antibodies could inhibit the growth of EMT-6 murine mammary
      tumor probably via an indirect mechanism that includes the depletion of estrogen.
      In view of these results, the protein vaccine Hsp65-GnRH(6) appears to be a
      promising candidate vaccine for hormone-dependent cancer therapy.

PMID- 20803012
TI  - Low-grade chondrosarcoma of bone: experiences from the Vienna Bone and Soft
      Tissue Tumour Registry.
AB  - In a retrospective single-centre study, 70 low-grade chondrosarcoma (LCS) (31
      female/39 male patients with a mean age of 40 years) were reviewed to evaluate
      surgical management. The mean overall follow-up was 81 months (median: 73 months,
      range: 6-317 months). Seventeen lesions (24.3%) in the trunk and 53 (75.7%) in
      the extremities were treated by curettage (48.6%) or resection (51.5%). Local
      recurrence occurred in eight patients (11.4%) 18 months postoperatively (median:
      18 months, range: 0-41 months). Recurrence-free survival was significantly better
      for patients with extremity lesions compared to truncal lesions, but was not
      affected by resection margin. The anatomical site "trunk" and an "intralesional"
      resection margin had a significant independent prognostic influence in
      multivariate analysis. Curettage with local adjuvants is a viable treatment
      option for most extremity LCS. In truncal LCS wide resection is recommended
      despite a potentially higher complication rate.

PMID- 20803013
TI  - Management of septic complications following modular endoprosthetic
      reconstruction of the proximal femur.
AB  - In a retrospective single-centre study 170 consecutive patients were included who
      received a Kotz modular prosthesis after resection of bone tumours of the
      proximal femur to evaluate the management of prosthetic infection. Infection
      occurred in 12 of 166 patients available for follow-up (six males; six females;
      mean age, 47 years; range, ten to 75 years) after a mean of 39 months (range, one
      to 166 months; infection rate, 7.2%). Mean follow-up was 54 months (range, four
      to 200 months). One patient died of septic shock. Two patients were treated by
      wound revision only. Treatment of infection in the remaining patients was one
      stage revision in eight and hip disarticulation in one. Infection control by one
      stage revision was achieved in five of eight patients; re-infection occurred in
      three patients and was successfully treated by further revision in all of them.
      The overall success rate for controlling infection was 83.3%.

PMID- 20803014
TI  - The risk injury to the posterior interosseous nerve in standard approaches to the
      proximal radius: a cadaver study.
AB  - PURPOSE: The aim of this study was to provide guidance on the safe zones for the
      exposure of the proximal radius by measuring the distance from the PIN to various
      anatomical landmarks in the proximal forearm in pronation and supination.
      METHODS: Twenty cadaveric arms were used for this study. On the anterior aspect
      of the forearm, the distance between insertion of the biceps tendon and the
      arcade of Frohse as well as the shortest distance between the PIN and the ulnar
      aspect of the radial neck were measured. On the posterior aspect of the forearm,
      the shortest distance between the PIN and the ulnar border of the interosseous
      membrane was measured at 30 and 50 mm distal to the articular surface of the
      radial head. RESULTS: The distance between the PIN and ulnar aspect of the radial
      neck had a mean of 21.6 mm in supination and 13.3 mm in pronation. The distance
      between the radial tuberosity and the arcade of Frohse was 18.6 mm. The mean
      distance between the PIN and the radial border of ulna at 30 mm distal to the
      articular surface of the proximal radius was 12.3 mm in supination and 22.3 mm in
      pronation. At 50 mm distal to the articular surface of the proximal radius the
      mean distance was 8 mm in supination and 16.2 mm in pronation. CONCLUSIONS: The
      course of this nerve is variable as it winds around the radial neck within the
      belly of the supinator muscle. Safe distances for dissection have been presented
      in our study.

PMID- 20803015
TI  - p53-Dependent anticancer effects of leptomycin B on lung adenocarcinoma.
AB  - PURPOSE: Leptomycin B (LMB) and/or its derivatives are considered a novel class
      of cancer therapeutics through blocking chromosome maintenance region 1, which
      mediates p53 nuclear export. The objectives of the present study were to first
      evaluate the cytotoxic effects of LMB on a normal human lung epithelial cell line
      (BEAS-2B) and three human lung adenocarcinoma cell lines with various p53 status
      (wild type: A549, mutant: NCI-H522, and null: NCI-H358) and then to identify LMB
      induced gene expression alterations in human p53 signaling pathway. METHODS:
      Cells were treated with 0.01-100 nM LMB or 0.1% ethanol (vehicle control) for 4
      72 h. Gene expression analyses using gene array for 84 genes involved in p53
      mediated signaling pathways were performed in A549 and NCI-H358 after treatment
      with 20 nM LMB or vehicle control for 24 h. RESULTS: Cytotoxic results from MTS
      assays revealed a significant dose- and time-dependent effect of LMB on all cell
      lines. However, this effect was more pronounced in cancer cells than in normal
      cells, and cancer cells with p53 wild type tended to be less sensitive than those
      with p53 mutant or null. A total of 23 genes, predominantly involved in apoptosis
      and cell cycle/proliferation, were significantly altered in A549 after LMB
      treatment, while no strong modulating effects were observed in NCI-H358. The
      protein expression of two selected genes, p21 and survivin, was further confirmed
      by Western blots. CONCLUSION: Our results suggest that LMB has anti-cancer
      potential and provides a new regimen of individualized therapy for lung cancer
      treatment.

PMID- 20803016
TI  - Phase II study of biweekly docetaxel and S-1 combination chemotherapy as first
      line treatment for advanced gastric cancer.
AB  - PURPOSE: We evaluated the efficacy and toxicity of biweekly S-1 and docetaxel
      combination therapy in patients with advanced gastric cancer. METHODS: Patients
      with histologically proven, unresectable advanced or recurrent gastric cancer, a
      performance status (PS) of 0-2 and no prior chemotherapy history were eligible
      for inclusion (n = 45). Patients received a total of 215 treatment courses
      (median, 4; range, 2-12) of S-1 oral administration twice daily for 1 week
      followed by a drug-free interval of 1 week. Docetaxel (40 mg/m(2)) was
      administered intravenously on days 1 and 15. RESULTS: We observed 25 partial
      responses (55.6%) and one complete response (2.2%), resulting in an overall
      response rate of 57.8%. Twenty-four patients (53.3%) received second-line
      chemotherapy. Five patients (11.1%) underwent R0 gastrectomy during the course of
      the study. The median overall survival time was 15.3 months, the median time to
      progression was 6.9 months, and the median duration of response in 26 patients
      was 8.0 months. Neutropenia was the most frequently observed (40.4%)
      haematological toxicity at grades 3 and 4 and leucopenia was the second most
      common (29.8%). There were no treatment-related deaths. CONCLUSIONS: S-1 plus
      docetaxel combination therapy in an outpatient setting provided promising
      activity with acceptable adverse toxicities.

PMID- 20803018
TI  - Serum uric acid predicts changes in reports of non-gouty chronic pain: a
      prospective study among women with inflammatory and non-inflammatory pain.
AB  - Widespread pain has earlier been associated with an increase in serum urate (SU).
      The aim of this study was to longitudinally study the relation between changes in
      pain reporting and the level of SU among women with chronic pain. Consecutive
      female patients (n = 124; aged 20-70 years), at rheumatology and rehabilitation
      practices, with chronic musculoskeletal pain of different origins were followed
      for 1 year with repeated blood samples and questionnaires. Complete data were
      obtained from 107 individuals. Factors that predicted an increase in pain
      extension during 12 months were studied in a logistic regression model. Changes
      in SU showed a significant correlation (r = 0.36) with changes in the number of
      reported pain locations. An initially high SU level (OR = 4.46), frequent use of
      alcohol (OR = 1.32) and a high number of pain locations (OR = 1.24) independently
      predicted an increase in pain extension during 12 months, whereas the use of
      steroids (OR = 0.21) in patients with inflammatory disorders resulted in a
      decreased number of reported pain locations. A relative increase in SU in
      combination with report of a high number of pain locations turned out to be a
      risk factor of increased pain extension in a cohort of women with chronic non
      gouty pain followed during 1 year. The importance of SU in relation to chronic
      pain and its prognosis needs to be validated in larger studies.

PMID- 20803020
TI  - [Mixed corneal dystrophy].
AB  - Clinical features of Fuchs' corneal endothelial dystrophy combined with lattice
      dystrophy were found in an 81-year-old patient who had been treated with anti
      inflammatory phosphate-rich eye drops. Histological analysis of the corneal
      button revealed Fuchs' corneal endothelial dystrophy, no evidence of lattice
      dystrophy but calcium deposits in the deep corneal stroma. This case demonstrates
      that calcium deposits can be incorporated in a grid-like pattern mimicking
      lattice dystrophy and supports the cautious use of phosphate-containing eye drops
      in the presence of chronic blepharoconjunctivitis and epithelial keratopathy.

PMID- 20803019
TI  - [Dry eye syndrome and neurotrophic keratitis in childhood. Causes and therapy].
AB  - PURPOSE: The purpose of this review is to enhance the physician's awareness of
      dry eye syndrome and neurotrophic keratitis in children, to describe the most
      frequently associated conditions and to discuss the diagnostic and therapeutic
      options available. METHODS: A literature review of the pathogenesis of dry eye
      syndrome and neurotrophic keratitis in children was carried out, clinical cases
      from our pediatric ophthalmology office are presented as well as therapeutic
      strategies. RESULTS: Diseases of the cornea and ocular surface such as dry eye
      syndrome, neurotrophic keratitis and corneal ulcers are infrequent in children
      compared to adults. However, they do occur and should be diagnosed and treated as
      soon as possible in order to prevent long-term complications and amblyopia.
      CONCLUSIONS: Inflammatory diseases of the ocular surface can be easily overlooked
      in children due to the often unknown spectrum of differential diagnoses and the
      frequently reduced cooperation during examination of young children. Correct and
      early diagnosis is essential for prevention of long-term complications, e.g.
      corneal ulceration and scarring.

PMID- 20803017
TI  - The many roles of NOX2 NADPH oxidase-derived ROS in immunity.
AB  - Reactive oxygen species (ROS) have long been studied in the context of their
      direct toxic effects on cells. As a result, ROS have conventionally been thought
      of as a necessary nuisance to aerobic living. However, in recent years, much work
      has been done to examine the contribution of ROS to the field of immunity.
      Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases were identified as
      one of the key sources of ROS in immune cells. The NOX2 NADPH oxidase in
      particular has been assigned multiple roles, functioning as a source of
      antimicrobial ROS, an activator of many signaling pathways, a participant in
      chemotaxis, an immune modulator, and a critical player in the initiation of
      antigen cross-presentation. Furthermore, recent studies have revealed a novel
      role for the NOX2 NADPH oxidase in the activation of autophagy, a cellular
      degradative pathway. Here, we examine these functions of NOX2 NADPH oxidase in
      immunity.

PMID- 20803021
TI  - Sex matters in echoacoustic orientation: gender differences in the use of
      acoustic landmarks in Phyllostomus discolor (lesser spear-nosed bat).
AB  - Sex-specific differences in orientation strategies are well known for several
      rodent and primate species with females relying more on landmarks when it comes
      to visually guided orientation, whereas males preferentially use Euclidean cues.
      We used the echolocating bat Phyllostomus discolor for a behavioural study on
      gender differences in the use of acoustic landmarks. The experimental animals (6
      males, 6 females) had to learn and perform a simple orientational task, firstly
      in the absence of landmarks and subsequently in the presence of four acoustic
      landmarks of which one was occasionally removed during the critical experiment.
      The results presented here show that gender differences in the use of acoustic
      landmarks exist in P. discolor, which supports our hypothesis that the phenomenon
      is independent of the modality that is used to sense the environment during
      orientation. Therefore, our findings allow for the prediction of similar
      phenomena in other acoustically orienting mammals. Interestingly, due to the
      specific ecology of P. discolor, our results partially contradict the
      evolutionary theories on gender-specific orientation, as will be discussed.
      Finally, we consider our finding as being one of several important steps toward
      establishing bats as a new model organism in neuroscientific studies on
      allocentric spatial cognition in mammals.

PMID- 20803023
TI  - Randomised, double-blind and placebo-controlled study using new probiotic
      lactobacilli for strengthening the body immune defence against viral infections.
AB  - BACKGROUND: The aim of this study was to investigate whether consumption of
      Lactobacillus plantarum HEAL 9 (DSM 15312) and Lactobacillus paracasei 8700:2
      (DSM 13434) could affect naturally acquired common cold infections in healthy
      subjects. METHODS: A randomised, parallel, double-blind placebo-controlled study
      was performed to investigate whether intake of this probiotic mixture could
      reduce the risk of common cold episodes, number of days with common cold
      symptoms, frequency and severity of symptoms, and cellular immune response in
      common cold infections. A total of 272 subjects were supplemented daily with
      either 10(9) cfu (colony forming units) of probiotics (N = 135) or control (N =
      137) for a 12-week period. RESULTS: The incidence of acquiring one or more common
      cold episode was reduced from 67% in the control group to 55% in the probiotic
      group (p < 0.05). Also, the number of days with common cold symptoms were
      significantly (p < 0.05) reduced from 8.6 days in the control group to 6.2 days,
      in the probiotic group, during the 12-week period. The total symptom score was
      reduced during the study period from a mean of 44.4 for the control group to 33.6
      for the probiotic group. The reduction in pharyngeal symptoms was significant (p
      < 0.05). In addition, the proliferation of B lymphocytes was significantly
      counteracted in the probiotic group (p < 0.05) in comparison with the control
      group. CONCLUSION: In conclusion, intake of the probiotic strains Lactobacillus
      plantarum HEAL 9 (DSM 15312) and Lactobacillus paracasei 8700:2 (DSM 13434)
      reduces the risk of acquiring common cold infections.

PMID- 20803022
TI  - Properties of cannabinoid-dependent long-term depression in the leech.
AB  - Previously, a cannabinoid-dependent form of long-term depression (LTD) was
      discovered at the polysynaptic connection between the touch mechanosensory neuron
      and the S interneuron (Li and Burrell in J Comp Physiol A 195:831-841, 2009). In
      the present study, the physiological properties of this cannabinoid-dependent LTD
      were examined. Increases in intracellular calcium in the S interneuron are
      necessary for this form of LTD in this circuit. Calcium signals contributing to
      cannabinoid-dependent LTD are mediated by voltage-dependent calcium channel and
      release of calcium from intracellular stores. Inositol triphosphate receptors,
      but not ryanodine receptors, appear to mediate this store-released calcium
      signal. Cannabinoid-dependent LTD also requires activation of metabotropic
      serotonin receptors, possibly a serotonin type 2-like receptor. Finally, this
      form of LTD involves the stimulation of nitric oxide synthase and a decrease in
      cyclic adenosine monophosphate signaling, both of which appeared to be downstream
      of cannabinoid receptor activation. Based on these findings, the cellular
      signaling mechanisms of cannabinoid-dependent LTD in the leech are remarkably
      similar to vertebrate forms of cannabinoid-dependent synaptic plasticity.

PMID- 20803024
TI  - [Pacemaker ECG Quiz No. 23: Pacemaker malfunction or arrhythmia?].
AB  - In a 69-year-old patient, a DDDR pacemaker was implanted for sinus node disease
      with syncope due to sinus arrest with pauses > 4 s. Programming was performed
      carefully including measures to prevent unnecessary ventricular pacing.
      Approximately 6 months after implantation, the patient who was asymptomatic in
      the meantime presented for pacemaker control because the ECG had raised the
      question of pacemaker malfunction.

PMID- 20803025
TI  - Cold paresis in multifocal motor neuropathy.
AB  - Increased weakness during cold (cold paresis) was reported in single cases of
      multifocal motor neuropathy (MMN). This was unexpected because demyelination is a
      feature of MMN and symptoms of demyelination improve, rather than worsen, in
      cold. It was hypothesized that cold paresis in MMN does not reflect demyelination
      only, but may indicate the existence of inflammatory nerve lesions with
      permanently depolarized axons that only just conduct at normal temperature, but
      fail at lower temperatures. We investigated symptoms of cold paresis in 50 MMN
      patients, 48 chronic inflammatory demyelinating polyneuropathy (CIDP) patients,
      35 progressive spinal muscular atrophy (PSMA) patients, and 25 chronic idiopathic
      axonal polyneuropathy patients. We also investigated symptoms of increased
      weakness during warmth (heat paresis). Cold paresis was reported more often than
      heat paresis. Cold paresis was most frequently reported in MMN. Multivariate
      analysis indicated that MMN patients had a 4- to 6-fold higher risk of reporting
      cold paresis than CIDP or PSMA patients. Because cold paresis is not consistent
      with demyelination, the lesions in MMN may involve other mechanisms than
      demyelination only. In conclusion, symptoms of cold paresis are common in
      peripheral nervous system disorders, particularly in MMN. This supports the above
      described hypothesis.

PMID- 20803026
TI  - Metabolism and regional cerebral blood volume in autoimmune inflammatory
      demyelinating lesions mimicking malignant gliomas.
AB  - Dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) and MR
      spectroscopy are thought to differentiate tumefactive autoimmune inflammatory
      demyelinating lesions from glial brain tumours. The aim of this work is to
      evaluate whether regional cerebral blood volume (rCBV), as well as choline (Cho),
      N-acetyl-aspartate (NAA) and myo-inositol (mIns) concentrations differ between
      tumefactive lesions and World Health Organization (WHO) grade II-III gliomas.
      Five patients with single autoimmune inflammatory demyelinating lesions and nine
      patients with WHO grade II and III gliomas were examined by DSC-MRI and by two
      dimensional (2D) 1H MR spectroscopic imaging (1H-MRSI). rCBV values and
      metabolite concentrations were normalised to the respective values of the
      contralateral hemisphere. Normalised rCBV in the tumefactive lesions (mean 2.89,
      range 1.98-6.74) was in the some high level as in gliomas (mean 2.77, range 1.43
      6.22). 1H-MRSI revealed increased normalised choline concentrations in five of
      six examinations of autoimmune lesions (mean 1.4, range 1.06-1.8) and in eight of
      nine gliomas (mean 1.35, range 0.92-1.73). Tumefactive autoimmune inflammatory
      demyelinating lesions not only have imaging appearance of gliomas but may also
      imitate marked increase of rCBV and Cho in WHO grade II-III gliomas.

PMID- 20803027
TI  - Deep brain stimulation for camptocormia in dystonia and Parkinson's disease.
AB  - Camptocormia, or "bent spine syndrome", may occur in various movement disorders
      such as primary dystonia or idiopathic Parkinson's disease (PD). Although deep
      brain stimulation (DBS) is an established treatment in refractory primary
      dystonia and advanced PD, few data are available on the effect of DBS on
      camptocormia comparing these two conditions. Seven patients (4 with dystonia, 3
      with PD; mean age 60.3 years at surgery, range 39-73 years) with camptocormia
      were included in the study. Five patients underwent bilateral GPi DBS and two
      patients underwent bilateral STN DBS guided by CT-stereotactic surgery and
      microelectrode recording. Pre- and postoperative motor assessment included the
      BFM in the dystonia patients and the UPDRS in the PD patients. Severity of
      camptocormia was assessed by the BFM subscore for the trunk at the last available
      follow-up at a mean of 17.3 months (range 9-36 months). There were no surgical
      complications. In the four patients with dystonia there was a mean improvement of
      53% in the BFM motor score (range 41-79%) and of 63% (range 50-67%) in the BFM
      subscore for the trunk at the last available follow-up (mean 14.3 months, range 9
      18 months). In the three patients with camptocormia in PD who underwent bilateral
      STN DBS (2 patients) or pallidal DBS (1 patient), the PD symptoms improved
      markedly (mean improvement in the UPDRS motor subscore stimulation on/medication
      off 55%, range 49-61%), but there was no or only mild improvement of camptocormia
      in the two patients who underwent STN DBS, and only moderate improvement in the
      patient with GPi DBS at the last available follow-up (mean 21 months, range 12-36
      months). GPi DBS is an effective treatment for camptocormia in dystonia. The
      response of camptocormia to chronic STN or GPi DBS in PD is more heterogenous.
      The latter may be due to a variety of causes and needs further clarification.

PMID- 20803028
TI  - Myofeedback training and intensive muscular strength training to decrease pain
      and improve work ability among female workers on long-term sick leave with neck
      pain: a randomized controlled trial.
AB  - The theoretical framework is that muscle tension in the neck is related to
      insufficient muscular rest and is a risk factor for chronic pain and reduced work
      ability. Promoting muscle strength and muscle rest may increase work ability and
      reduce neck pain. OBJECTIVES: To test whether myofeedback training or intensive
      strength training leads to decreased pain and increased work ability in women on
      long-term sick leave. METHODS: This is a randomized controlled trial of two 1
      month interventions with myofeedback or muscular strength training in the home
      environment. Female human service organization workers (n = 60) on long-term (>60
      days) sick leave and with chronic neck pain were followed with self-reported and
      laboratory-observed data of health, pain, muscular activation, and work ability,
      at baseline, immediately after the intervention and 3 months after baseline.
      RESULTS: For both intervention groups, pain was lowered over time compared with
      the control group. Decreased pain and muscular activity was associated with
      increased self-rated work ability and with laboratory-observed work ability at 3
      month follow-up. Decreased pain was also associated with increased self-rated
      work ability at 1-month follow-up. Muscular strength training was associated with
      increased self-rated work ability and mental health. Myofeedback was associated
      with increased observed work ability and self- rated vitality. CONCLUSIONS: The
      two interventions showed positive results, suggesting that they could be
      developed for use in health care practice to address pain and work ability. The
      intensive muscular strength training program, which is both easy to conduct at
      home and easy to coach, was associated with increased work ability.

PMID- 20803029
TI  - Aggressive approach to acinar cell carcinoma of the pancreas: a single
      institution experience and a literature review.
AB  - PURPOSE: Acinar cell carcinomas (ACCs) are a rare pancreatic tumor group with no
      standardized treatment. The aim of the study is to analyze the clinical and
      pathologic characteristics of our series and to review the current literature.
      METHODS: Retrospective review of prospectively collected data from 1990 to 2007
      included patients who underwent pancreatic resection for histologically proven
      ACCs. All specimens of ACC were rereviewed by an expert pathologist. Follow-up
      was updated to October 2009. A literature search was performed by Pubmed and
      COCHRANE library. RESULTS: Among 1,210 patients who underwent pancreatic
      resection, we identified nine ACCs. R0 resection was possible for all but one R1.
      We had no major complications and no mortality. All nine cases were diagnosed as
      pure ACCs. Five patients received adjuvant chemotherapy. Median overall survival
      was 31 months, while median disease-free survival was 18 months. All patients
      developed liver metastases, requiring modification of chemotherapeutic schema,
      radiofrequency ablation techniques, or reiterate surgery. Currently, only one
      patient is alive without evidence of disease 85 months after pancreatic
      resection. One patient is alive 52 months after operation, with evidence of
      recurrent disease. CONCLUSIONS: ACC represents a rare solid tumor of the
      pancreas. Prognosis is dismal, although, compared to the more common ductal
      adenocarcinoma, survival appears to be longer. Patients with metastatic disease
      might benefit from aggressive multimodality treatments.

PMID- 20803030
TI  - Usefulness of tissue microarrays for assessment of protein expression, gene copy
      number and mutational status of EGFR in lung adenocarcinoma.
AB  - Specific inhibitors targeting the epidermal growth factor receptor (EGFR) can
      increase survival rates in certain lung adenocarcinoma patients with mutations in
      the EGFR gene. Although such EGFR-targeted therapies have been approved for use,
      there is no general consensus among surgical pathologists on how the EGFR status
      should be tested in lung adenocarcinoma tissues and whether the results of
      immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and
      mutational analysis by molecular methods correlate. We evaluated the EGFR status
      in 61 lung adenocarcinomas by IHC (using total and mutant-specific antibodies
      against EGFR), by FISH analysis on tissue microarrays (TMAs), and by direct
      sequencing. The results of each method were compared using chi2 and kappaappa
      statistics. The sensitivity and negative predictive value estimating the presence
      of abnormal EGFR for each test was calculated. The results show that, with
      respect to expression patterns and clinicopathological parameters, the total and
      mutant-specific EGFR detected by immunohistochemistry and FISH analysis on TMAs
      are valid and are equivalent to conventional methods performed on whole-tissue
      sections. Abnormal EGFR was detected in 52.4% of patients by IHC, FISH, and
      sequencing. The best sensitivity (100%) and negative predictive value (100%) was
      determined by evaluating the EGFR status with all methods. Testing for molecular
      changes in EGFR using a single test is likely to underestimate the presence of
      EGFR abnormalities. Taken together, these results demonstrate the high potential
      of TMAs to test for the major mechanisms of EGFR activation in patients with lung
      adenocarcinoma.

PMID- 20803032
TI  - A boy with a one-sided red rash.
AB  - We report on a boy with a sudden onset of unilateral skin lesions following
      tonsillar infection with fever 2 weeks before. The lesions consisted of
      erythematous macules with scaling affecting trunk, axillar, as well as inguinal
      region. CRP, blood differential, serum IgG and IgM antibodies (coxsackievirus,
      cytomegalovirus, parvovirus, herpes virus, varicella zoster virus, human
      herpesvirus-6/-7), and lesional swabs (bacteria, dermatophytes, yeasts) were
      uneventful.

PMID- 20803031
TI  - Mucin core protein expression in serrated polyps of the large intestine.
AB  - Sessile serrated adenoma (SSA) has been proposed as a precursor to microsatellite
      unstable colorectal carcinoma. However, histological criteria dictating how to
      differentiate serrated lesions have not been completely established, and a
      histological overlap exists between SSA and hyperplastic polyps (HPs),
      particularly the microvesicular type. In this study, based on a critical review
      of histology, we aimed to elucidate the potential utility of the mucin phenotype
      in the identification of SSA. We evaluated mucin core protein expression (MUC2,
      MUC5AC, and MUC6) by immunohistochemical stain in 65 cases of microvesicular-type
      HPs, 51 SSAs, and 72 traditional serrated adenomas (TSAs). SSAs had
      clinicopathological and morphological features distinct from those of HPs and
      TSAs. MUC6 was more frequently positive in SSAs (39%) than in TSAs (4%) and HPs
      (19%) (P < 0.001 and P = 0.0107, respectively). Right-sided HPs more frequently
      expressed MUC6 than did left-sided HPs (60% vs. 4%, respectively; P < 0.0001),
      but SSAs and TSAs showed no regional differences. These findings suggest that
      determination of mucin core protein expression is insufficient for
      differentiating SSAs from other types of serrated polyps, and that microvesicular
      type HPs of the right colon and SSAs may belong to the same mucin spectrum.

PMID- 20803033
TI  - Methane flux dynamics during mire succession.
AB  - Vegetation, temperature and hydrology are major factors controlling wetland
      methane (CH(4)) dynamics. In order to test their importance, we measured CH(4)
      emissions and environmental characteristics over 2 years from five mires
      representing a successional sequence, ranging in age from 178 to 2,520 years. We
      hypothesized CH(4) emissions to be higher from the sedge-dominated fens than from
      the older bog stage. The more constant hydrological conditions at later
      successional stages as a consequence of the thicker peat layer appeared to result
      in lower temporal variation in CH(4) emissions. Accordingly, the other controls,
      temperature and vegetation, had an effect on CH(4) emissions only when the water
      table was sufficiently high. The seasonal variation in CH(4) emissions was
      controlled by temperature only at the oldest study site, which had the lowest
      variation in water table. Within-season variation in emissions related to plant
      phenology was highest at the fen stage, which was dominated by aerenchymatous
      plants with a strong seasonal pattern, namely sedges and forbs. In contrast to
      our hypothesis, CH(4) emissions increased with mire age towards the bog stage.
      However, the trend did not emerge during a rainy growing season, due to a rise in
      CH(4) emissions at the younger stages. The results may imply two different
      mechanisms during mire succession: while old mires are able to avoid the
      perturbation associated with variation in the water table and maintain their
      function as CH(4) emitters, young mires are exposed to perturbation but are able
      to recover their function.

PMID- 20803034
TI  - Microfiltration conditions modify Lactobacillus bulgaricus cryotolerance in
      response to physiological changes.
AB  - This work aimed at analyzing the effect of microfiltration conditions (cross-flow
      velocity and transmembrane pressure) on the quality of frozen Lactobacillus
      bulgaricus CFL1 starters produced on pilot scale. Microfiltered cells were less
      resistant during the concentration process than centrifuged cells. In contrast,
      bacterial cryotolerance during freezing was improved after microfiltration, in a
      range of 28-88%, depending on the microfiltration conditions. During frozen
      storage, cell resistance was also affected by microfiltration conditions, either
      positively or negatively, compared to centrifugation. The best cryotolerance was
      obtained for cells microfiltered at a cross-flow velocity of 2 m/s and a
      transmembrane pressure of 0.15 MPa. This improvement was explained by considering
      membrane fatty acid composition of Lb. bulgaricus CFL1. This condition increased
      unsaturated to saturated and cyclic to saturated fatty acid ratios, which
      enhanced membrane fluidity, thus helping the cells to better resist freezing and
      frozen storage.

PMID- 20803036
TI  - Complementary therapies for supportive cancer care.

PMID- 20803035
TI  - Sunny hours and variations in the prevalence of asthma in schoolchildren
      according to the International Study of Asthma and Allergies (ISAAC) Phase III in
      Spain.
AB  - The objective of this study was to estimate the relationship between the
      prevalence of asthma in schoolchildren aged 6-7 years and 13-14 years and the
      mean annual sunny hours (MASH) in Spain, and to explore predictive models for
      asthma prevalence. The prevalence of asthma was obtained from the International
      Study of Asthma and Allergies (ISAAC) Phase III 2002-2003, and climate and socio
      economic variables from official sources. Nine centres were studied and a further
      four centres, two of which are in ISAAC, to test the predictive models. Logistic
      regression was used to estimate adjusted prevalence rates of asthma for each
      centre, and multiple regression models to study the effects of MASH and other
      meteorological and socio-economic variables. The adjusted prevalence rate of
      asthma decreased 0.6% [95% confidence interval (CI) 0.4-0.8%] for the 6-7 years
      group and 1.1% (95% CI 0.8-1.3%) for the 13-14 years group with an increase in
      the MASH of 100 h. Relative humidity was negatively associated with asthma in the
      older age group, and gross province product per capita (GPP) was positively
      associated with asthma in the younger age group. The predictive models, which
      included MASH, gender, relative humidity, and GPP, anticipated prevalence rates
      of asthma without significant differences between the levels observed and those
      expected in 9 of the 11 measurements carried out. The results indicate that sunny
      hours have a protective effect on the prevalence of asthma in schoolchildren.

PMID- 20803037
TI  - The diagnostic value of CRP, IL-8, PCT, and sTREM-1 in the detection of bacterial
      infections in pediatric oncology patients with febrile neutropenia.
AB  - PURPOSE: In this study, we evaluated C-reactive protein (CRP), interleukin (IL)
      8, procalcitonin (PCT), and soluble triggering receptor expressed on myeloid
      cells-1 (sTREM-1) as predictors for bacterial infection in febrile neutropenia,
      plus their usefulness in febrile neutropenia during chemotherapy-induced
      gastrointestinal mucositis. METHODS: Plasma was obtained from pediatric oncology
      patients at presentation with febrile neutropenia (n = 43) and 24-48 h later (n =
      17). The patients were classified as having or not having a bacterial infection.
      Plasma was also obtained of patients in the absence and in the presence of
      mucositis (n = 26). RESULTS: At presentation with febrile neutropenia, median IL
      8 and PCT levels were significantly increased in patients with a bacterial
      infection, in contrast to CRP and sTREM-1. IL-8 was the most sensitive marker for
      the early detection of bacterial infection, in combination with clinical
      parameters or PCT the sensitivity reached 100%. After 24-48 h, only PCT was
      significantly elevated during bacterial infection. IL-8 levels were significantly
      increased during mucositis. Mucositis did not cause considerable changes in PCT
      levels. CONCLUSIONS: IL-8 is the most useful marker for the early detection of
      bacterial infections, compared with CRP, PCT, and sTREM-1. IL-8 in combination
      with clinical parameters or PCT might be even more useful. Gastrointestinal
      mucositis alone does not affect PCT levels, in contrast to IL-8 levels, and
      therefore, PCT might be more useful for the detection of bacterial infections
      during mucositis than IL-8.

PMID- 20803038
TI  - No impact of central venous insertion site on oncology patients' quality of life
      and psychological distress. A randomized three-arm trial.
AB  - PURPOSE: Though totally implantable access ports (TIAP) are extensively used,
      information from randomized trials about the impact of insertion site on
      patient's quality of life (QoL) and psychological distress is unavailable.
      PATIENTS AND METHODS: Four hundred and three patients eligible for receiving
      intravenous chemotherapy for solid tumours were randomly assigned to implantation
      of a single type of TIAP, either through a percutaneous landmark access to the
      internal jugular or an ultrasound-guided access to the subclavian or a surgical
      cut-down access through the cephalic vein at the deltoid-pectoralis groove.
      Patients' QoL and psychological distress were investigated at regular intervals
      by means of EORTC QLQ-C30 and HADS (Hospital Anxiety and Depression Scale)
      questionnaires, using univariate and multivariate repeated measure linear mixed
      models. A post hoc analysis investigated the impact of type of administered
      chemotherapy (adjuvant vs palliative). RESULTS: Three hundred and eighty-four
      patients (95.2%) were evaluable, 126 with the internal jugular, 132 with the
      subclavian and 126 with the cephalic vein access. The median follow-up was 361
      days (range, 0-1,087). Mean score changes for the items of the EORTC QLQ-C30
      scales were significantly associated with type of administered chemotherapy only
      (P < 0.001), and not with implantation site. Frequency distribution of patients
      with depression and anxiety score greater than 10 at HADS was not significantly
      different, with respect either to type of administered chemotherapy or TIAP
      implantation site. CONCLUSION: Central venous insertion sites had no impact on
      patients' QoL and psychological distress. Patients undergoing palliative
      therapies showed worse EORTC QLQ-C30 scales.

PMID- 20803040
TI  - Methods for large-scale production of AM fungi: past, present, and future.
AB  - Many different cultivation techniques and inoculum products of the plant
      beneficial arbuscular mycorrhizal (AM) fungi have been developed in the last
      decades. Soil- and substrate-based production techniques as well as substrate
      free culture techniques (hydroponics and aeroponics) and in vitro cultivation
      methods have all been attempted for the large-scale production of AM fungi. In
      this review, we describe the principal in vivo and in vitro production methods
      that have been developed so far. We present the parameters that are critical for
      optimal production, discuss the advantages and disadvantages of the methods, and
      highlight their most probable sectors of application.

PMID- 20803039
TI  - Consensus recommendations for the prevention of vomiting and nausea following
      high-emetic-risk chemotherapy.
AB  - In this update of our 2005 document, we used an evidence-based approach whenever
      possible to formulate recommendations, emphasizing the results of controlled
      trials concerning the best use of antiemetic agents for the prevention of emesis
      and nausea following anticancer chemotherapies of high emetic risk. A three-drug
      combination of a 5-hydroxytryptamine type 3 receptor (5-HT(3)) receptor
      antagonist, dexamethasone, and aprepitant beginning before chemotherapy and
      continuing for up to 4 days remains the standard of care. We address issues of
      dose, schedule, and route of administration of five selective 5-HT(3) receptor
      antagonists. We conclude that, for each of these five drugs, there is a plateau
      in therapeutic efficacy above which further dose escalation does not improve
      outcome. In trials designed to prove the equivalence of palonosetron to
      ondansetron and granisetron, palonosetron proved superior in emesis prevention,
      while adverse effects were comparable. Furthermore, for all classes of antiemetic
      agents, a single dose is as effective as multiple doses or a continuous infusion.
      The oral route is as efficacious as the intravenous route of administration.

PMID- 20803041
TI  - Dose-dependent ultrastructural and morphometric alterations after erythropoietin
      treatment in rat femoral artery vasospasm model.
AB  - PURPOSE: Cerebral vasospasm is the common cause of poor outcome after aneurysmal
      subarachnoid hemorrhage (aSAH). Although many agents are experimentally and
      clinicaly used to protect or recover from vasospasm, an effective
      neurotherapeutic drug is still missing. Erythropoietin (EPO) is recently a
      promising candidate. The aim of this study is to investigate the dose-dependent
      effects of recombinant human EPO (rhEPO) on arterial wall in a rat femoral artery
      vasospasm model. METHODS: Thirty two animals were divided into four groups:
      vasospasm without any treatment (group A), vasospasm +250 IU/kg rhEPO group
      (group B), vasospasm +500 IU/kg rhEPO group (group C), and control group (group
      D). Rat femoral artery vasospasm model was used. For groups B and C, 7 days of
      250 IU/kg and 500 IU/kg intraperitoneal rhEPO in 0.3 ml saline were administered
      respectively; and for groups A and D, 0.3 ml saline were administered
      intraperitoneally without any treatment. After 7 days, histological and
      morphometric analyses were carried out. RESULTS: Vasospasm alone group
      demonstrated the highest vessel wall thicknesses, comparing to other groups (p <
      0.001). While for groups B and C, vessel wall thickness values were significantly
      higher than the control group (p < 0.001), between these two groups, there was no
      significant difference achieved (p > 0.05). CONCLUSION: In our study, there was
      no significant difference between the two rhEPO treatment groups, but rhEPO
      treatment was shown to be histologically and morphometrically effective in
      vasospasm. However, if dosage of EPO treatment is augmented, successful results
      may be achieved.

PMID- 20803042
TI  - Surveillance for European bat lyssavirus in Swiss bats.
AB  - Most countries in Western Europe are currently free of rabies in terrestrial
      mammals. Nevertheless, rabies remains a residual risk to public health due to the
      natural circulation of bat-specific viruses, such as European bat lyssaviruses
      (EBLVs). European bat lyssavirus types 1 and 2 (EBLV-1 and EBLV-2) are widely
      distributed throughout Europe, but little is known of their true prevalence and
      epidemiology. We report that only three out of 837 brains taken from bats
      submitted to the Swiss Rabies Centre between 1976 and 2009 were found by
      immunofluorescence (FAT) to be positive for EBLVs. All three positive cases were
      in Myotis daubentoni, from 1992, 1993 and 2002. In addition to this passive
      surveillance, we undertook a targeted survey in 2009, aimed at detecting
      lyssaviruses in live bats in Switzerland. A total of 237 bats of the species M.
      daubentoni, Myotis myotis, Eptesicus serotinus and Nyctalus noctula were captured
      at different sites in western Switzerland. Oropharyngeal swabs and blood from
      each individual were analysed by RT-PCR and rapid fluorescent focus inhibition
      test (RFFIT), respectively. RNA corresponding to EBLV-2 was detected from
      oropharyngeal swabs of a single M. daubentoni bat, but no infectious virus was
      found. Molecular phylogenetic analysis revealed that the corresponding sequence
      was closely related to the other EBLV-2 sequences identified in previous rabies
      isolates from Swiss bats (particularly to that found at Geneva in 2002). Three M.
      daubentoni bats were found to be seropositive by RFFIT. In conclusion, even
      though the prevalence is low in Switzerland, continuous management and
      surveillance are required to assess the potential risk to public health.

PMID- 20803043
TI  - Recurrent inguinal hernia in a preschool girl treated laparoscopically with a
      preperitoneal transabdominal technique and polypropylene mesh: an alternative in
      complex cases.
AB  - We report the case of a 4-year-old girl treated by a laparoscopic transabdominal
      preperitoneal (TAPP) technique with polypropylene mesh in whom a primary
      contralateral hernia was found and repaired, closing the orifice with a suture.
      This 4-year-old female had a medical history of clubfoot treated by surgery
      during her first year of age, ureteral reimplantation because of stenosis, and
      laparoscopic cholecystectomy because of hydrocholecystis. She had recurrence 1
      year after a conventional inguinal herniorraphy and was treated by the TAPP
      technique with polypropylene mesh. A primary contralateral hernia was found and
      repaired, and the orifice was closed with a suture. The child's acceptance of the
      procedure was good, and the postoperative evolution was uneventful, requiring
      minimal analgesia in the first 24 h. She was discharged the following day. Two
      years later, there have been no recurrences, and the girl is developing and
      carrying out activities in a normal way. The open technique remains the gold
      standard for hernioplasty in children, but laparoscopy may be an option, and it
      is possible that in some special cases, the use of mesh to reinforce the inguinal
      wall using the TAPP technique, although it is controversial, may be justified.

PMID- 20803044
TI  - Traumatic lumbar hernia repair: a laparoscopic technique for mesh fixation with
      an iliac crest suture anchor.
AB  - Traumatic lumbar hernia (TLH) is a rare presentation. Traditionally, these have
      been repaired via an open approach. Recurrence can be a problem due to the often
      limited tissue available for mesh fixation at the inferior aspect of the hernia
      defect. We report the successful use of bone suture anchors placed in the iliac
      crest during transperitoneal laparoscopy for mesh fixation to repair a recurrent
      TLH. This technique may be particularly useful after previous failed attempts at
      open TLH repair.

PMID- 20803045
TI  - Assessment of fatigue in Moroccan patients with ankylosing spondylitis.
AB  - This study aims to assess fatigue aspects in Moroccan patients with ankylosing
      spondylitis (AS), and its relationships with disease-specific variables of
      activity and severity. A cross-sectional study included patients with ankylosing
      spondylitis according to New York Classification criteria for the diagnosis of
      AS. To assess fatigue, the first item of Bath Ankylosing Spondylitis Disease
      Activity index (BASDAI) and the Multidimensional assessment of fatigue were used
      (MAF). The evaluation included the activity of the disease (BASDAI), global well
      being (Bath Ankylosing Spondylitis Global Index), functional status (Bath
      Ankylosing Spondylitis Functional Index), enthesitis and health-related quality
      of life (SF-36 generic instrument). One hundred patients were included (67 men
      and 33 women), of average age 38.0 years +/- 12.9 [18-72]. Our patients had a
      moderately active and a severe disease. In our data, 60% experienced severe
      fatigue (BASDAI fatigue >= 50 mm) and mean total score of MAF = 32.0 +/- 20.
      Gender, NSAID therapy and the presence of biological inflammatory syndrome did
      not influence the MAF scores. Higher scores of fatigue were correlated with
      functional disability, general well-being, disease activity, enthesitis, and the
      deterioration of five domains of SF-36. Multivariate regression showed strong
      relationship between fatigue severity and general well-being and enthesitis.
      Severe fatigue (MAF) was most related with the domain of physical function. This
      study state the importance of fatigue in AS patients. The severity of fatigue is
      associated with disease activity, functional disability, general well-being, and
      enthesitis. Fatigue influences negatively different aspects of quality of life.
      Fatigue is an important outcome measure that must be part of routine clinical
      evaluation of our AS patients.

PMID- 20803046
TI  - Rapid identification of yeasts from positive blood culture bottles by
      pyrosequencing.
AB  - We have developed a rapid protocol for the identification of Candida species from
      positive blood cultures by combining a simple method for nucleic acid extraction
      and preparation using microbial storage cardboards with polymerase chain reaction
      (PCR) and pyrosequencing of a small region of the 18 S rRNA gene. The protocol is
      robust and easy to implement and can be performed in 4 h. The method was tested
      against a collection of clinical blood cultures. Agreement of sequence
      identifications with standard microbiological methods was 100%.

PMID- 20803047
TI  - Correlation of the in vitro antifungal drug susceptibility with the in vivo
      activity of fluconazole in a murine model of cerebral infection caused by
      Cryptococcus gattii.
AB  - Forty Cryptococcus gattii strains were submitted to antifungal susceptibility
      testing with fluconazole, itraconazole, amphotericin B and terbinafine. The
      minimum inhibitory concentration (MIC) ranges were 0.5-64.0 for fluconazole,
      <0.015-0.25 for itraconazole, 0.015-0.5 for amphotericin B and 0.062-2.0 for
      terbinafine. A bioassay for the quantitation of fluconazole in murine brain
      tissue was developed. Swiss mice received daily injections of the antifungal, and
      their brains were withdrawn at different times over the 14-day study period. The
      drug concentrations varied from 12.98 to 44.60 MUg/mL. This assay was used to
      evaluate the therapy with fluconazole in a model of infection caused by C.
      gattii. Swiss mice were infected intracranially and treated with fluconazole for
      7, 10 or 14 days. The treatment reduced the fungal burden, but an increase in
      fungal growth was observed on day 14. The MIC for fluconazole against sequential
      isolates was 16 MUg/mL, except for the isolates obtained from animals treated for
      14 days (MIC = 64 MUg/mL). The quantitation of cytokines revealed a predominance
      of IFN-gamma and IL-12 in the non-treated group and elevation of IL-4 and IL-10
      in the treated group. Our data revealed the possibility of acquired resistance
      during the antifungal drug therapy.

PMID- 20803048
TI  - Posttraumatic transcalvarial brain herniation into the eyelid.

PMID- 20803049
TI  - A fatal Mycobacterium chelonae infection in an immunosuppressed patient with
      systemic lupus erythematosus and concomitant Fahr's syndrome.
AB  - We present a case of systemic Mycobacterium chelonae infection in an
      immunosuppressed patient with systemic lupus erythematosus (SLE), idiopathic
      hypoparathyroidism, and hypothyroidism. The patient was treated for 3 months for
      skin infection with clarithromycin monotherapy. Since her condition deteriorated,
      the antibiotic therapy was switched to intravenously administered clindamycin,
      cloxacillin, and meropenem. Due to further deterioration and isolation of M.
      chelonae from the blood culture, antimicrobial therapy was changed to
      azithromycin and amikacin. Drug-test sensitivity was performed, and the isolate
      was susceptible to clarithromycin only. The patient's deteriorating status
      prevented orally administered medication with clarithromycin (parenteral
      formulation is not registered in Croatia). The same antibiotic regime was
      continued until the isolation of Pseudomonas aeruginosa and Candida albicans. In
      addition, extensive calcifications in her brain were found on a computed
      tomography (CT) scan, which suggested Fahr's syndrome. Despite all measures and
      supportive care, the patient developed multiorgan failure and eventually died.
      There has been an increase in the number of infections by rapidly growing
      mycobacteria, but only a few cases of severe systemic infection with M. chelonae
      have been described. If the infection is diagnosed early and a patient is treated
      with appropriate drugs, dissemination can be avoided despite immunosuppression.
      For serious skin, bone, and soft-tissue disease, a minimum of 4 months of a
      combined drug therapy is necessary. This is the first report of M. chelonae
      infection in Croatia and the first-described M. chelonae infection in a patient
      with concomitant Fahr's syndrome.

PMID- 20803050
TI  - Reimbursement of pharmaceuticals: reference pricing versus health technology
      assessment.
AB  - Reference pricing and health technology assessment are policies commonly applied
      in order to obtain more value for money from pharmaceuticals. This study focussed
      on decisions about the initial price and reimbursement status of innovative drugs
      and discussed the consequences for market access and cost. Four countries were
      studied: Germany, The Netherlands, Sweden and the United Kingdom. These countries
      have operated one, or both, of the two policies at certain points in time,
      sometimes in parallel. Drugs in four groups were considered: cholesterol-lowering
      agents, insulin analogues, biologic drugs for rheumatoid arthritis and "atypical"
      drugs for schizophrenia. Compared with HTA, reference pricing is a relatively
      blunt instrument for obtaining value for money from pharmaceuticals. Thus, its
      role in making reimbursement decisions should be limited to drugs which are
      therapeutically equivalent. HTA is a superior strategy for obtaining value for
      money because it addresses not only price but also the appropriate indications
      for the use of the drug and the relation between additional value and additional
      costs. However, given the relatively higher costs of conducting HTAs, the most
      efficient approach might be a combination of both policies.

PMID- 20803051
TI  - Optimization of culture conditions for mycoepoxydiene production by Phomopsis sp.
      Hant25.
AB  - Culture media and fermentation conditions for cultivation of an endophytic fungus
      Phomopsis sp. Hant25 were investigated in order to improve the yield of
      mycoepoxydiene, a novel fungal metabolite having potent cytotoxic activity
      against many cancer cell lines. Mycoepoxydiene accumulated in the culture broth
      during the stationary phase of fungal growth. Modified M1D medium was superior to
      malt Czapek, and Czapek yeast autolysate broths in supporting mycoepoxydiene
      production. Pellet growth was the morphological form that favored biosynthesis of
      mycoepoxydiene. This could be achieved by incubating the culture statically for 6
      days before shaking at 120 rpm. Incorporation of a cellulose paper disc into the
      culture flask promoted fungal growth at the liquid surface, which accelerated
      mycoepoxydiene production and maximized the final yield to a level of 354 mg l-1,
      though fungal attachment to the solid support was not required. Since the peak
      concentration of mycoepoxydiene in the culture broth was followed by a steeply
      declining phase, the harvest time had to be precisely determined for maximum
      product yield. Understanding the factor(s) involved in rapid degradation of
      mycoepoxydiene could lead to improved final yields.

PMID- 20803052
TI  - Gemcitabine plus sorafenib in patients with advanced pancreatic cancer: a phase
      II trial of the University of Chicago Phase II Consortium.
AB  - BACKGROUND: Sorafenib, an inhibitor of B-raf, VEGFR2, and PDGFR-beta, has
      activity against pancreatic cancer in preclinical models. In a phase I trial of
      gemcitabine plus sorafenib, 57% of pancreatic cancer patients achieved stable
      disease. PATIENTS AND METHODS: We conducted a multi-center phase II trial of
      sorafenib plus gemcitabine in chemo-naive patients with histologically-confirmed,
      advanced pancreatic cancer. Patients received sorafenib 400 mg twice daily and
      gemcitabine 1,000 mg/m(2) on days 1, 8 and 15 of a 28 day cycle. RESULTS:
      Seventeen patients enrolled at 4 centers; 13 were evaluable for response. There
      were no objective responses; 18% had stable disease. Median overall survival was
      4.0 months (95% CI: 3.4, 5.9); median progression-free survival was 3.2 months
      (95% CI: 1.6, 3.6). Grade 3/4 toxicities included thrombosis in 18% of patients,
      dehydration or hand-foot syndrome in 12%, and hypertension or gastrointestinal
      bleeding in 6%. CONCLUSION: Gemcitabine plus sorafenib is inactive in advanced
      pancreatic cancer.

PMID- 20803053
TI  - Influence of metal cofactors and water on the catalytic mechanism of creatininase
      creatinine in aqueous solution from molecular dynamics simulation and quantum
      study.
AB  - The reaction mechanism of creatinine-creatininase binding to form creatine as a
      final product has been investigated by using a combined ab initio quantum
      mechanical/molecular mechanical approach and classical molecular dynamics (MD)
      simulations. In MD simulations, an X-ray crystal structure of the
      creatininase/creatinine was modified for creatininase/creatinine complexes and
      the MD simulations were run for free creatininase and creatinine in water. MD
      results reveal that two X-ray water molecules can be retained in the active site
      as catalytic water. The binding free energy from Molecular Mechanics Poisson
      Boltzmann Surface Area calculation predicted the strong binding of creatinine
      with Zn2+, Asp45 and Glu183. Two step mechanisms via Mn2+/Zn2+ (as in X-ray
      structure) and Zn2+/Zn2+ were proposed for water adding step and ring opening
      step with two catalytic waters. The pathway using synchronous transit methods
      with local density approximations with PWC functional for the fragment in the
      active region were obtained. Preferable pathway Zn2+/Zn2+ was observed due to
      lower activation energy in water adding step. The calculated energy in the second
      step for both systems were comparable with the barrier of 26.03 and 24.44
      kcal/mol for Mn2+/Zn2+ and Zn2+/Zn2+, respectively.

PMID- 20803056
TI  - Upregulation of coronary endothelial P-selectin in a monkey heart ischemia
      reperfusion model.
AB  - The design of targeted ultrasound contrast agents for molecular imaging of
      myocardial ischemia-reperfusion (IR) requires the availability of an adequate in
      vivo model in a species in which cross reactivity with the target occurs. P
      selectin (Psel) is an activation-dependent endothelial receptor that supports
      rapid and reversible cell adhesion in a flowing system. Together with E- and L
      selectins it constitutes the selectin family of adhesion molecules. We
      investigated the myocardial expression of selectins in a closed chest minimally
      invasive monkey myocardial IR model. Catheter-based occlusion (30-50 min)
      followed by reperfusion (3 or 5 h) of left anterior descending artery (LAD) was
      performed in anesthetised monkeys. At the end of each procedure animals were
      killed, and their hearts were excised. The tissues were analyzed
      immunohistochemically using an anti-human Psel antibody (AK-6 clone) that cross
      reacts with rhesus monkey. Histopathological features confirm the presence of IR
      injuries in myocardial tissues. There was significant increase in the Psel
      expression in vessels from the IR areas. However, significantly higher Psel
      immunoreactivity was also seen in areas which are distant from IR injuries.

PMID- 20803054
TI  - Tomato-based food products for prostate cancer prevention: what have we learned?
AB  - Evidence derived from a vast array of laboratory studies and epidemiological
      investigations have implicated diets rich in fruits and vegetables with a reduced
      risk of certain cancers. However, these approaches cannot demonstrate causal
      relationships and there is a paucity of randomized, controlled trials due to the
      difficulties involved with executing studies of food and behavioral change.
      Rather than pursuing the definitive intervention trials that are necessary, the
      thrust of research in recent decades has been driven by a reductionist approach
      focusing upon the identification of bioactive components in fruits and vegetables
      with the subsequent development of single agents using a pharmacologic approach.
      At this point in time, there are no chemopreventive strategies that are standard
      of care in medical practice that have resulted from this approach. This review
      describes an alternative approach focusing upon development of tomato-based food
      products for human clinical trials targeting cancer prevention and as an adjunct
      to therapy. Tomatoes are a source of bioactive phytochemicals and are widely
      consumed. The phytochemical pattern of tomato products can be manipulated to
      optimize anticancer activity through genetics, horticultural techniques, and food
      processing. The opportunity to develop a highly consistent tomato-based food
      product rich in anticancer phytochemicals for clinical trials targeting specific
      cancers, particularly the prostate, necessitates the interactive
      transdisciplinary research efforts of horticulturalists, food technologists,
      cancer biologists, and clinical translational investigators.

PMID- 20803057
TI  - Analysis of the intracellular localization of p73 N-terminal protein isoforms
      TAp73 and ?Np73 in medulloblastoma cell lines.
AB  - The protein homologous to the tumor suppressor p53, p73, has essential roles in
      development and tumorigenesis. This protein exists in a wide range of isoforms
      with different, even antagonistic, functions. However, there are virtually no
      detailed morphological studies analyzing the endogenous expression of p73
      isoforms at the cellular level in cancer cells. In this study, we investigated
      the expression and subcellular distribution of two N-terminal isoforms, TAp73 and
      DeltaNp73, in medulloblastoma cells using immunofluorescence microscopy. Both
      proteins were observed in all cell lines examined, but differences were noted in
      their intracellular localization between the reference Daoy cell line and four
      newly established medulloblastoma cell lines (MBL-03, MBL-06, MBL-07 and MBL-10).
      In the new cell lines, TAp73 and DeltaNp73 were located predominantly in cell
      nuclei. However, there was heterogeneity in TAp73 distribution in the cells of
      all MBL cell lines, with the protein located in the nucleus and also in a limited
      non-random area in the cytoplasm. In a small percentage of cells, we detected
      cytoplasmic localization of TAp73 only, i.e., nuclear exclusion was observed. Our
      results provide a basis for future studies on the causes and function of distinct
      intracellular localization of p73 protein isoforms with respect to different
      protein-protein interactions in medulloblastoma cells.

PMID- 20803058
TI  - Striated muscle tropomyosin isoforms differentially regulate cardiac performance
      and myofilament calcium sensitivity.
AB  - Tropomyosin (TM) plays a central role in calcium mediated striated muscle
      contraction. There are three muscle TM isoforms: alpha-TM, beta-TM, and gamma-TM.
      alpha-TM is the predominant cardiac and skeletal muscle isoform. beta-TM is
      expressed in skeletal and embryonic cardiac muscle. gamma-TM is expressed in slow
      twitch musculature, but is not found in the heart. Our previous work established
      that muscle TM isoforms confer different physiological properties to the cardiac
      sarcomere. To determine whether one of these isoforms is dominant in dictating
      its functional properties, we generated single and double transgenic mice
      expressing beta-TM and/or gamma-TM in the heart, in addition to the endogenously
      expressed alpha-TM. Results show significant TM protein expression in the
      betagamma-DTG hearts: alpha-TM: 36%, beta-TM: 32%, and gamma-TM: 32%. These
      betagamma-DTG mice do not develop pathological abnormalities; however, they
      exhibit a hyper contractile phenotype with decreased myofilament calcium
      sensitivity, similar to gamma-TM transgenic hearts. Biophysical studies indicate
      that gamma-TM is more rigid than either alpha-TM or beta-TM. This is the first
      report showing that with approximately equivalent levels of expression within the
      same tissue, there is a functional dominance of gamma-TM over alpha-TM or beta-TM
      in regulating physiological performance of the striated muscle sarcomere. In
      addition to the effect expression of gamma-TM has on Ca(2+) activation of the
      cardiac myofilaments, our data demonstrates an effect on cooperative activation
      of the thin filament by strongly bound rigor cross-bridges. This is significant
      in relation to current ideas on the control mechanism of the steep relation
      between Ca(2+) and tension.

PMID- 20803059
TI  - The efficacy of a modified Theory of Reasoned Action to explain gambling behavior
      in college students.
AB  - Recently, Thrasher et al. (College Student Affairs Journal 27(1): 57-75, 2007)
      explored the efficacy of the Theory of Reasoned Action (TRA; Ajzen and Fishbein,
      Attitudes, personality, and behavior, 1980) in explaining gambling behavior of
      college students. However, their study found the TRA only predicted small amounts
      of variance in gambling intentions. Heeding their call to enhance the efficacy of
      the TRA through the addition of explanatory variables to the model, the present
      study incorporated gambling motivations and locus of control as moderating
      variables within the TRA to test the potential of a modified TRA in explaining
      gambling behavior of college students. A total of 345 students at a major
      metropolitan research university in the Midwest volunteered to participate in the
      study. A series of hierarchical linear regressions indicated intrinsic motivation
      to accomplish (p = .002) significantly moderated the relationship between
      gambling attitudes and gambling intentions. Further, internal locus of control (p
      < .001), chance locus of control (p < .001), and powerful others locus of control
      (p < .001) also significantly moderated the relationship between gambling
      attitudes and gambling intentions. The significant impact of the moderating
      variables on the relationship between gambling attitudes and intentions suggests
      intrinsic motivation and locus of control can alter the impact of the
      relationship between gambling attitudes and gambling intentions.

PMID- 20803061
TI  - Introduction of an expert system for the discrimination of local pulmonary vein
      and atrial far field signals.
AB  - BACKGROUND: Discrimination of local and far field potentials during sinus rhythm
      and atrial fibrillation (AF) is essential for successful pulmonary vein (PV)
      isolation. We sought to introduce an expert system for the classification of
      electrophysiologic PV signals. METHODS: For the expert system database, we
      analyzed ablation procedures of 50 patients with paroxysmal and persistent AF.
      Standard circumferential catheters and bipolar recordings were required. In a
      prospective trial, the expert system was compared with the performing
      electrophysiologists' classifications of potentials during 15 procedures. A total
      of 1,343 recordings of local PV and far field signals were validated by the
      sudden disappearance of local potentials during ablation, the presence of
      dissociated PV activity, and pacing maneuvers. A fast Fourier transform was
      applied to the individual potentials. Analysis continued in the amplitude and
      phase representation. RESULTS: Four parameters significant (p < 0.001) for
      classification were identified and entered a logistic regression model. Overall
      sensitivity and specificity of the model was 87% with minor, nonsignificant
      variations for individual PVs and different underlying rhythms. Concordance with
      ad hoc electrophysiologists' classification of local potentials was 70%, which
      increased during post hoc analysis to 86% since classification of 14% of the
      potentials had to be revised. For these potentials, the expert system correctly
      predicted their local origin in 86%. CONCLUSION: An expert system for the
      evaluation of electrophysiologic signals based on morphology analysis using the
      Fourier transform is feasible. The ease of use and online availability facilitate
      a widespread use for AF ablation procedures.

PMID- 20803060
TI  - Partitioning the resistances along the vascular tree: effects of dobutamine and
      hypovolemia in piglets with an intact circulation.
AB  - OBJECTIVE: We present a new physiological model that discriminated between
      changes in the systemic arterial and venous circulation. To test our model, we
      studied the effects of dobutamine and hypovolemia in intact pentabarbital
      anesthetized piglets. METHODS: Aorta pressure (Pao), central venous pressure
      (Pcv), mean systemic filling pressure (Pmsf) and cardiac output (CO), were
      measured in 10 piglets, before, during and after dobutamine infusion (6 ug kg-1
      min-1), as well as during hypovolemia (-10 mL kg-1), and after fluid
      resuscitation to normovolemia. Venous (Rv) and total systemic (Rsys) resistance
      were determined from Pao, Pcv, Pmsf and CO. The quotient of Rv/Rsys was used to
      determine the predominant location of vascular changes (i.e. vasoconstriction or
      dilatation on either venous or arterial side). RESULTS: Administration of
      dobutamine increased heart rate and CO, whereas it decreased Pmsf, Rsys, Rv and
      Rv/Rsys. The decrease in Rv was significantly greater than Rsys. Pao and Pcv did
      not change. Hypovolemia decreased CO, Pcv, Pmsf, Rv and Rv/Rsys, but kept Rsys
      constant and increased heart rate. CONCLUSIONS: Hypovolemia and dobutamine
      differentially alter Pmsf, Rsys, Rv and Rv/Rsys ratio. The increase in CO during
      dobutamine infusion was attributed to the combined increased cardiac function and
      decreased Rv. The decrease in CO with hypovolemia was due to a decreased Pmsf but
      was partly compensated for by a decrease in Rv tending to preserve venous return
      and thus CO.

PMID- 20803062
TI  - Genome sequence of the temperate bacteriophage PH10 from Streptococcus oralis.
AB  - Exponential growing cultures of Streptococcus oralis strain OMZ 1038, isolated
      from human supragingival dental plaque, were found to release a bacteriophage
      (designated PH10) upon treatment with mitomycin C. The complete genome sequence
      of phage PH10 was determined. The genome was 31276 bp in size and contained 54
      open reading frames. The module encoding structural proteins was highly similar
      to that of Streptococcus pneumoniae prophage PhiSpn_3. The most abundant phage
      structural protein was encoded by ORF35 and was likely processed by proteolytic
      cleavage. The putative endolysin from PH10, which contained a muramidase domain
      and a choline-binding domain, was purified and shown to have lytic activity with
      S. oralis, S. pneumoniae and Streptococcus mitis, but not with other
      streptococcal species.

PMID- 20803063
TI  - People with HIV in HAART-era Russia: transmission risk behavior prevalence,
      antiretroviral medication-taking, and psychosocial distress.
AB  - Russia has seen one of the world's fastest-growing HIV epidemics. Transmission
      risk behavior, HAART-taking, and psychosocial distress of the growing population
      of Russian people living with HIV (PLH) in the HAART era are understudied.
      Participants of a systematically-recruited cross-sectional sample of 492 PLH in
      St. Petersburg completed measures of sexual and drug injection practices,
      adherence, perceived discrimination, and psychosocial distress. Since learning of
      their status, 58% of participants had partners of HIV-negative or unknown
      serostatus (mean = 5.8). About 52% reported unprotected intercourse with such
      partners, with 30% of acts unprotected. Greater perceived discrimination
      predicted lower condom use. A 47% of IDU PLH still shared needles, predicted by
      having no primary partner, lower education, and more frequently-encountered
      discrimination. Twenty-five percentage of PLH had been refused general health
      care, 11% refused employment, 7% fired, and 6% forced from family homes. Thirty
      nine percentage of participants had probable clinical depression, 37% had anxiety
      levels comparable to psychiatric inpatients, and social support was low. Of the
      54% of PLH who were offered HAART, 16% refused HAART regimens, and 5% of those on
      the therapy took less than 90% of their doses. Comprehensive community services
      for Russian PLH are needed to reduce AIDS-related psychosocial distress and
      continued HIV transmission risk behaviors. Social programs should reduce stigma
      and discrimination, and promote social integration of affected persons and their
      families.

PMID- 20803064
TI  - Local perceptions of the forms, timing and causes of behavior change in response
      to the AIDS epidemic in Zimbabwe.
AB  - Quantitative studies indicate that HIV incidence in Zimbabwe declined since the
      late 1990s, due in part to behavior change. This qualitative study, involving
      focus group discussions with 200 women and men, two dozen key informant
      interviews, and historical mapping of HIV prevention programs, found that
      exposure to relatives and close friends dying of AIDS, leading to increased
      perceived HIV risk, was the principal explanation for behavior change. Growing
      poverty, which reduced men's ability to afford multiple partners, was also
      commonly cited as contributing to reductions in casual, commercial and extra
      marital sex. HIV prevention programs and services were secondarily mentioned as
      having contributed but no specific activities were consistently indicated,
      although some popular culture influences appear pivotal. This qualitative study
      found that behavior change resulted primarily from increased interpersonal
      communication about HIV due to high personal exposure to AIDS mortality and a
      correct understanding of sexual HIV transmission, due to relatively high
      education levels and probably also to information provided by HIV programs.

PMID- 20803065
TI  - Regional and seasonal influence in patient's toxicity to adjuvant chemotherapy
      for early breast cancer.
AB  - Results from multinational clinical trials are globally adopted into the routine
      clinical practice in most countries. Changes in the natural history and incidence
      of certain diseases as well as in drugs toxicities related to yearly seasons have
      been reported, however, variations related to climate have never been described.
      In our study, we assessed whether yearly seasons and climate could influence the
      chemotherapy toxicity profile. We analyzed the toxicities recorded in the phase
      III GEICAM 9906 study which was run in different geographically and
      climatically/seasonally regions in Spain. In this trial 1246 patients were
      randomized and eligible to receive FEC90 *6 cycles or FEC90 *4 cycles followed by
      eight doses of weekly paclitaxel (T). The results showed differences in
      hematological and non-hematological toxicities in relation to the season of the
      year and the climate of the area in which the treatment was administered. We
      found a higher hematological toxicity in warm seasons (spring and summer) and in
      Oceanic climate regions (Neutropenia G4: 7.8 vs. 1.0 vs. 1.0%, P < 0.0001).
      Asthenia was greater frequency in the summer period (FEC90: 21.1%, T: 15.3%) as
      well as in the Mediterranean areas (FEC: 28% T: 27.2%). Also we observed liver
      transaminase elevations were more frequent in the summer and in the Oceanic
      areas. Myalgias and secondary sensory neuropathy to paclitaxel were recorded more
      frequently during autumn. Climate should be considered a significant variable in
      toxicity to chemotherapy.

PMID- 20803067
TI  - Approaches and limitations of phosphatidylinositol-3-kinase pathway activation
      status as a predictive biomarker in the clinical development of targeted therapy.
AB  - The central role played by the class I(A) phosphatidylinositol-3-kinase (PI3K)
      signaling node in human cancer is highlighted in the multiple mechanisms by which
      these signals become dysregulated. Many studies suggest that constitutive PI3K
      activation in human cancer contributes to drug resistance, including targeted
      agents and standard cytotoxic therapy. The combination of activation mechanisms
      and the multiple downstream cascades that emanate from the PI3K node contributes
      to the difficulty in measuring PI3K activation as a biomarker. Although many
      agents suppress the pathway in models, the challenge remains to translate this
      biology into a patient selection strategy (i.e., identify patients with "PI3K
      activated" tumors) and subsequently link this biomarker definition to drug
      responses in patients. The various genetic and epigenetic lesions resulting in
      pathway activation necessitate combined approaches using genetic, genomic, and
      protein biomarkers to accurately characterize "PI3K activated" tumors. Such a
      combined approach to pathway status can be assessed using a statistical
      stratification of patients in a randomized trial into "pathway on" and "pathway
      off" subsets to compare the treatment effect in each arm. Instead of considering
      individual biomarkers for their predictive ability, this strategy proposes the
      use of a collection of biomarkers to identify a specific "pathway on" patient
      population predicted to have clinical benefit from a pathway inhibitor. Here, we
      review the current understanding of the mechanisms of PI3K activation in breast
      cancer and discuss a pathway-based approach using PI3K as a predictive biomarker
      in clinical development, which is currently in use in a global phase 3 setting.

PMID- 20803066
TI  - Early discontinuation and non-adherence to adjuvant hormonal therapy are
      associated with increased mortality in women with breast cancer.
AB  - Despite the benefit of adjuvant hormonal therapy (HT) on mortality among women
      with breast cancer (BC), many women are non-adherent with its use. We
      investigated the effects of early discontinuation and non-adherence to HT on
      mortality in women enrolled in Kaiser Permanente of Northern California (KPNC).
      We identified women diagnosed with hormone-sensitive stage I-III BC, 1996-2007,
      and used automated pharmacy records to identify prescriptions and dates of
      refill. We categorized patients as having discontinued HT early if 180 days
      elapsed from the prior prescription. For those who continued, we categorized
      patients as adherent if the medication possession ratio was >=80%. We used Cox
      proportional hazards models to estimate the association between discontinuation
      and non-adherence with all-cause mortality. Among 8,769 women who filled at least
      one prescription for HT, 2,761 (31%) discontinued therapy. Of those who continued
      HT, 1,684 (28%) were non-adherent. During a median follow-up of 4.4 years, 813
      women died. Estimated survival at 10 years was 80.7% for women who continued HT
      versus 73.6% for those who discontinued (P < 0.001). Of those who continued,
      survival at 10 years was 81.7 and 77.8% in women who adhered and non-adhered,
      respectively (P < 0.001). Adjusting for clinical and demographic variables, both
      early discontinuation (HR 1.26, 95% CI 1.09-1.46) and non-adherence (HR 1.49, 95%
      CI 1.23-1.81), among those who continued, were independent predictors of
      mortality. Both early discontinuation and non-adherence to HT were common and
      associated with increased mortality. Interventions to improve continuation of and
      adherence to HT may be critical to improve BC survival.

PMID- 20803068
TI  - Haemato-immunology and histo-architectural changes in Labeo rohita fingerlings:
      effect of dietary aflatoxin and mould inhibitor.
AB  - A feeding trail of 60 days was conducted for delineating the effect of dietary
      aflatoxin (AFB1) with or without supplementation of a mixture of mould inhibitor
      (0.25% clove oil + 0.32% sodium propionate) on haematology, respiratory burst
      activity and histology of Labeo rohita fingerlings. Three hundred and sixty
      fishes (avg. wt. 1.48-1.54 g) were randomly distributed into eight treatment
      groups. Eight experimental diets with four different levels of aflatoxin (0, 10,
      20 and 40 ppb) with or without mould inhibitor were prepared. Haematological
      parameters like total serum protein, albumin, globulin and A:G ratio were
      significantly (P < 0.05) reduced with increasing levels of aflatoxin in the diet.
      However, supplementation of mould inhibitor showed enhanced values when compared
      to non-supplemented counter parts suggesting ameliorating effects of mould
      inhibitor on aflatoxin. Total leucocyte count was higher in aflatoxin-treated
      groups. Histological observations were complementary to haematological
      parameters. Respiratory burst activity was significantly (P < 0.05) decreased in
      higher aflatoxin-treated groups but not affected significantly (P > 0.05) due to
      inclusion of inhibitor alone and/or interaction of aflatoxin level and inhibitor
      in the diet. From this study, it was concluded that up to 20 ppb aflatoxin level
      in the diet the haemato-immunological parameters are protected.

PMID- 20803070
TI  - Synthesis of 18O-labeled photosynthetically active chlorophylls at the 3- or 7
      carbonyl group with high regioselectivity.
AB  - The 3- and 7-formyl groups of chlorophyll-d (Chl-d) and bacteriochlorophyll-e
      (BChl-e), respectively, were regioselectively labeled with an isotopically stable
      oxygen-18 (18O) atom to give 31-18O-labeled Chl-d and 71-18O-labeled BChl-e (ca.
      90% 18O) by exchanging the carbonyl oxygen atoms in the presence of acidic H2 18O
      (ca. 95% 18O). Another photosynthetically active chlorophyll, BChl-a possessing
      the 3-acetyl group was treated under similar acidic conditions to afford a trace
      amount of 31-18O-labeled BChl-a and further demetallated compound, the
      corresponding 31-18O-labeled bacteriopheophytin-a as the major product with 55%
      18O-degree. The FT-IR spectra of 18O-(un)labeled chlorophylls in the solution and
      the solid states showed that the 3- and 7-carbonyl stretching vibration modes
      moved to about a 30-cm-1 lower wavenumber by 18O-labeling at the 31- and 71-oxo
      moieties. In artificial chlorosome-like self-aggregates of BChl-e, the 18O
      labeled 7-carbonyl stretching mode was completely resolved from the specially
      hydrogen-bonded 13-C=O stretching mode, evidently indicating no interaction of
      the 7-CHO with other functional groups in the supramolecules.

PMID- 20803069
TI  - Neonatal administration of thimerosal causes persistent changes in mu opioid
      receptors in the rat brain.
AB  - Thimerosal added to some pediatric vaccines is suspected in pathogenesis of
      several neurodevelopmental disorders. Our previous study showed that thimerosal
      administered to suckling rats causes persistent, endogenous opioid-mediated
      hypoalgesia. Here we examined, using immunohistochemical staining technique, the
      density of MU-opioid receptors (MORs) in the brains of rats, which in the second
      postnatal week received four i.m. injections of thimerosal at doses 12, 240,
      1,440 or 3,000 MUg Hg/kg. The periaqueductal gray, caudate putamen and
      hippocampus were examined. Thimerosal administration caused dose-dependent
      statistically significant increase in MOR densities in the periaqueductal gray
      and caudate putamen, but decrease in the dentate gyrus, where it was accompanied
      by the presence of degenerating neurons and loss of synaptic vesicle marker
      (synaptophysin). These data document that exposure to thimerosal during early
      postnatal life produces lasting alterations in the densities of brain opioid
      receptors along with other neuropathological changes, which may disturb brain
      development.

PMID- 20803071
TI  - Increasing healthy behaviors in adolescents of Mexican heritage in rural emerging
      Latino communities: results from a school-based health intervention pilot study.
AB  - The rapid Latino population growth in emerging Latino communities (EmLCs)
      presents a challenge to health care providers as most current health
      interventions and health promotion programs intended for Latinas/os are based on
      characteristics of established Latino communities (EsLCs). This study addresses
      the gap in the literature by modifying and testing the beginning efficacy of a
      school-based health intervention for adolescents of Mexican heritage in a rural
      EmLC. Seventy adolescents of Mexican heritage attending a rural middle school
      participated in the intervention. Paired samples t-tests were performed to
      determine differences between healthy behaviors at post-intervention compared to
      pre-intervention. Significant improvements in participants' physical activity and
      healthy eating were observed between pre-intervention and post-intervention. A
      school-based health intervention designed to increase healthy behaviors of
      adolescents of Mexican heritage in a rural EmLC was successful.

PMID- 20803072
TI  - I believe I am so called: reflections on a vocation in medical education.
AB  - This essay is concerned with the fulfillment of ordination commitments through a
      pastoral role in medical education and review of medical research with human
      subjects. Stylistically, it combines memoir with the genre known as "creative non
      fiction." Its major issues have to do with the identity formation and
      transformation of the author, the function and ethics of institutional review
      boards, the teaching of medical ethics to medical students, and courses involved
      in the doctor-patient relationship and in palliative care intended to increase
      the sensitivity and self-awareness of physicians-in-becoming. This essay was
      presented in its initial form at the Annual Fellows Meeting of the Society for
      Values in Higher Education in 2010.

PMID- 20803073
TI  - Locus of control beliefs mediate the relationship between religious functioning
      and psychological health.
AB  - Theistic and spiritually based beliefs and behaviors have been demonstrated to
      consistently predict physical and mental health, although the psychological
      processes underlying these relationships are unclear. This study investigated
      associative relationships and pathways of mediation between religious
      functioning, locus of control (LOC) and health. The sample consisted of 122
      Christians (79 women, 43 men) who were predominately Catholic, ranging in age
      from 18 to 80 (M = 45.47, SD = 15.0). Participants were recruited from churches
      in the Western suburbs of Melbourne, Australia, and completed a questionnaire
      package measuring (1) psychological and physical health, (2) the religious
      variables of awareness of God, instability and impression management, and (3)
      God, internal and external LOC domains. Results indicated that awareness of God
      and internal LOC were associated with better health, whereas external LOC and
      instability were associated with poorer health. God LOC and impression management
      were not significantly associated with health. Sobel tests were used to analyse
      mediation hypotheses. Internal LOC was found to mediate the relationship between
      awareness of God and better psychological health, and external LOC was found to
      mediate the relationship between instability and poorer psychological health.
      These findings are of considerable clinical significance.

PMID- 20803074
TI  - Poor Little Ritz Boy David "does" Hawaii or: lucky Davy salutes lucky Lindy.
AB  - In this article, David Bittner explodes the myth, restated in Brideshead
      Revisited (1945), that Polynesians are "happy and harmless." He does so for the
      same reason that Evelyn Waugh does: "the grim invasion of trader, administrator,
      missionary, and tourist" has changed all that (p. 174). Touring Hawaii in July of
      '09, Bittner was interested to discover some unusual bits of American heritage,
      but saddened to see how "civilization" and "Americanization" actually seem to
      have eroded the Hawaiian people's rights to life, liberty, and the pursuit of
      happiness. Bittner's dual religious heritage-Judaism by birth and upbringing and
      Catholicism by choice in mid-life-has given him the perspective to apply the
      lessons of Hawaiian history to his own personal issues, particularly forgiveness.

PMID- 20803075
TI  - Government influence on patient organizations.
AB  - Patient organizations increasingly play an important role in health care decision
      making in Western countries. The Netherlands is one of the countries where this
      trend has gone furthest. In the literature some problems are identified, such as
      instrumental use of patient organizations by care providers, health insurers and
      the pharmaceutical industry. To strengthen the position of patient organizations
      government funding is often recommended as a solution. In this paper we analyze
      the ties between Dutch government and Dutch patient organizations to learn more
      about the effects of such a relationship between government and this part of
      civil society. Our study is based on official government documents and existing
      empirical research on patient organizations. We found that government influence
      on patient organizations has become quite substantial with government influencing
      the organizational structure of patient organizations, the activities these
      organizations perform and even their ideology. Financing patient organizations
      offers the government an important means to hold them accountable. Although the
      ties between patient organizations and the government enable the former to play a
      role that can be valued as positive by both parties, we argue that they raise
      problems as well which warrant a discussion on how much government influence on
      civil society is acceptable.

PMID- 20803078
TI  - 2010 SSO presidential address: subspecialty certificate in advanced surgical
      oncology.

PMID- 20803079
TI  - Sentinel node biopsy in squamous-cell carcinoma of the anal canal.
AB  - BACKGROUND: Radiochemotherapy is the standard treatment for patients with
      carcinoma of the anal canal. Therefore, a surgical specimen is not usually
      obtained. Inguinal lymph node metastases cannot be accurately predicted by either
      clinical examination or imaging techniques. In this study, we applied the
      sentinel node technique in patients with anal canal squamous-cell carcinoma to
      determine whether this provided more reliable staging of tumors. METHODS: From
      May 2007 to May 2009, we enrolled 11 patients (7 women) with a mean age 65 (range
      39-80) years with squamous-cell carcinoma of the anal canal and clinically and
      radiologically negative groin lymph nodes. The patients were staged with
      endorectal ultrasound, computed tomographic scan, magnetic resonance imaging of
      the pelvis, and positron emission tomography. There were two T1, four T2, and
      five T3 tumors (International Union Against Cancer classification).
      Lymphoscintigraphy with peritumoral 99mTc colloid injection was performed 16 to
      18 h before surgery. During the surgery, patent blue dye was injected
      peritumorally, and the sentinel inguinal node was identified by a handheld gamma
      probe and dye visualization. RESULTS: The sentinel lymph node was detected in all
      11 patients by scintigraphy; in 9 cases, the lymph node was in the inguinal
      region. All of these patients underwent radioguided node biopsy, and a total of
      12 lymph nodes were removed. The average diameter of the resected nodes was 8
      (range 4-20) mm. No serious complications occurred. In three patients, metastases
      were identified in the lymph node. CONCLUSIONS: Sentinel node biopsy is a more
      accurate method than clinical or radiological techniques to stage the disease of
      patients with anal carcinoma.

PMID- 20803080
TI  - FOXC2 is a novel prognostic factor in human esophageal squamous cell carcinoma.
AB  - BACKGROUND: FOXC2 has been implicated in cancer progression through its induction
      of epithelial-to-mesenchymal transition. We analyzed the clinical significance of
      FOXC2 in esophageal cancer cases, in which early distant metastasis or invasion
      to nearby organs is an obstacle to treatment. METHODS: Quantitative reverse
      transcriptase-polymerase chain reaction was used to evaluate FOXC2 mRNA
      expression in 70 esophageal cancer cases to determine the clinicopathologic
      significance of FOXC2 expression. Furthermore, we examined associations between
      FOXC2 expression and matrix metalloproteinases 2 (MMP2) and matrix
      metalloproteinases 9 (MMP9). We also performed in vitro invasion and migration
      assays for FOXC2-suppressed esophageal cancer cells. RESULTS: In
      clinicopathologic analysis, the high-FOXC2 expression group showed a higher
      incidence of advanced tumor stage, lymph node metastasis, and lymphatic invasion
      than the low-FOXC2 expression group (P < 0.05). In particular, tumor stage
      exhibited the most remarkable difference (P < 0.0001). Expression of MMP2 and
      MMP9 was far higher in the high-FOXC2 expression group. Furthermore, the high
      FOXC2 expression group had a significantly poorer prognosis than did the low
      expression group (P = 0.006). Multivariate analysis indicated that high FOXC2
      expression was an independent prognostic factor for survival. Suppression of
      FOXC2 expression altered the invasive and the migratory ability of esophageal
      cancer cells in vitro. CONCLUSIONS: Our findings suggest that FOXC2 could be an
      important prognostic indicator for esophageal cancer patients. FOXC2 is directly
      involved in cancer progression and is associated with poor prognosis in
      esophageal cancer cases.

PMID- 20803081
TI  - mTOR signaling is involved in indomethacin and nimesulide suppression of
      colorectal cancer cell growth via a COX-2 independent pathway.
AB  - BACKGROUND: Inhibition of mammalian target of rapamycin (mTOR) represents an
      attractive target for anticancer therapy, but its role in suppression of
      colorectal cancer (CRC) cell growth by cyclooxygenase-2 (COX-2) inhibitors is
      unclear. Here, we analyzed the effect of indomethacin (Indo, a nonselective COX-2
      inhibitor) and nimesulide (Nim, a selective COX-2 inhibitor) on mTOR signaling in
      CRC cells in vitro and in vivo to determine the dependence of this effect on COX
      2. METHODS: Human CRC cell lines with varying COX-2 expression levels were
      treated with Indo and Nim. Western blot test was performed to detect mTOR-related
      components (mTOR, p70s6 K, and 4EBP1), and cell viability, cell cycle, and
      apoptosis were assessed. HCT116 and SW1116 cells were injected into athymic nude
      mice to establish a CRC xenograft model. After treatment with Nim, tumor volume,
      mTOR signaling, and apoptosis were evaluated in this model. HT29 and SW1116 cells
      were also treated with Nim after transfection with COX-2-specific small
      interfering RNA (siRNA) to assess dependence of COX-2 on mTOR signaling under
      drug treatment. RESULTS: Both Indo and Nim reduced mTOR signaling activity in CRC
      cells that differ in their COX-2 expression in vitro and in vivo. Additionally,
      Indo and Nim could reduce the mTOR signaling activity after COX-2 silencing in
      CRC cells. CONCLUSIONS: mTOR signaling is involved in Indo- and Nim-mediated
      suppression of CRC growth via a COX-2 independent pathway. This study unveils a
      novel mechanism through which COX-2 inhibitors exerts their anticancer effects
      and further emphasizes targeting mTOR signaling in anticancer therapy.

PMID- 20803082
TI  - Quercetin enhances human alpha7 nicotinic acetylcholine receptor-mediated ion
      current through interactions with Ca(2+) binding sites.
AB  - The flavonoid quercetin is a low molecular weight substance found in fruits and
      vegetables. Aside from its anti-oxidative effect, quercetin, like other
      flavonoids, has a wide range of neuropharmacological actions. The alpha7
      nicotinic acetylcholine receptor (alpha7 nAChR) has a Ca(2+)-binding site, is
      highly permeable to the Ca(2+) ion, and plays important roles in Ca(2+)-related
      normal brain functions. Dysfunctions of alpha7 nAChR are associated with a
      variety of neurological disorders. In the present study, we investigated the
      effects of quercetin on the ACh-induced inward peak current (I(ACh)) in Xenopus
      oocytes that heterologously express human alpha7 nAChR. I(ACh) was measured with
      the two-electrode voltage clamp technique. In oocytes injected with alpha7 nAChR
      cRNA, the effects of the co-application of quercetin on I(ACh) were concentration
      dependent and reversible. The ED(50) was 36.1 + 6.1 MUM. Quercetin-mediated
      enhancement of I(ACh) caused more potentiation when quercetin was pre-applied.
      The degree of I(ACh) potentiation by quercetin pre-application was time-dependent
      and saturated after 1 min. Quercetin-mediated I(ACh) enhancement was not affected
      by ACh concentration and was voltage-independent. However, quercetin-mediated
      I(ACh) enhancement was dependent on extracellular Ca(2+) concentrations and was
      specific to the Ca(2+) ion, since the removal of extracellular Ca(2+) or the
      addition of Ba(2+) instead of Ca(2+) greatly diminished quercetin enhancement of
      I(ACh). The mutation of Glu195 to Gln195, in the Ca(2+)-binding site, almost
      completely diminished quercetin-mediated I(ACh) enhancement. These results
      indicate that quercetin-mediated I(ACh) enhancement human alpha7 nAChR
      heterologously expressed in Xenopus oocytes could be achieved through
      interactions with the Ca(2+)-binding site of the receptor.

PMID- 20803083
TI  - Calcineurin regulates coelomocyte endocytosis via DYN-1 and CUP-4 in
      Caenorhabditis elegans.
AB  - C. elegans coelomocytes are macrophage-like scavenger cells that provide an
      excellent in vivo system for the study of clathrin-mediated endocytosis. Using
      this in vivo system, several genes involved in coelomocyte endocytosis have been
      identified previously. However, the detailed mechanism of endocytic pathway is
      still unknown. Here, we report a new function of calcineurin, an evolutionarily
      conserved Ca(2+)/calmodulin-dependent Ser/Thr protein phosphatase, in coelomocyte
      endocytosis. We found that calcineurin mutants show defective coelomocyte
      endocytosis. Genetic analysis suggests that calcineurin and a GTPase, dynamin
      (DYN-1), may function upstream of an orphan receptor, CUP-4, to regulate
      endocytosis. Therefore, we propose a model in which calcineurin may regulate
      coelomocyte endocytosis via DYN-1 and CUP-4 in C. elegans.

PMID- 20803084
TI  - An Arabidopsis splicing RNP variant STEP1 regulates telomere length homeostasis
      by restricting access of nuclease and telomerase.
AB  - Telomere is an essential DNA-protein complex composed of repetitive DNA and
      binding proteins to protect the chromosomal ends in eukaryotes. Telomere length
      is regulated by a specialized RNA-dependent DNA polymerase, telomerase and
      associated proteins. We show here a potential role of STEP1 that was previously
      isolated by affinity chromatography in controlling telomere length. While STEP1
      requires both RNA-binding domains for telomere binding and subsequent DNA
      protection, it requires only one RBD to interact with telomerase. The
      differential telomerase inhibitory activity depending on STEP1 concentrations may
      suggest that STEP1 contributes to controlling telomere length homeostasis, likely
      by limiting the accessibility of nuclease or telomerase to telomeric DNA.

PMID- 20803085
TI  - Overexpression of the ethylene-responsive factor gene BrERF4 from Brassica rapa
      increases tolerance to salt and drought in Arabidopsis plants.
AB  - Ethylene-responsive factors (ERFs), within a subgroup of the AP2/ERF
      transcription factor family, are involved in diverse plant reactions to biotic or
      abiotic stresses. Here, we report that overexpression of an ERF gene from
      Brassica rapa ssp. pekinensis (BrERF4) led to improved tolerance to salt and
      drought stresses in Arabidopsis. It also significantly affected the growth and
      development of transgenic plants. We detected that salt-induced expressions of a
      transcriptional repressor gene, AtERF4, and some Ser/Thr protein phosphatase2C
      genes, ABI1, ABI2 and AtPP2CA, were suppressed in BrERF4-overexpressing
      Arabidopsis plants. Furthermore, BrERF4 was induced by treatment with ethylene or
      methyljasmonate, but not by abscisic acid or NaCl in B. rapa. These results
      suggest that BrERF4 is activated through a network of different signaling
      pathways in response to salinity and drought.

PMID- 20803086
TI  - MKP1 regulates the induction of MCP1 by Streptococcus pneumoniae pneumolysin in
      human epithelial cells.
AB  - Epithelial cells act as the first line of host defense against microbes by
      producing a range of different molecules for clearance. Chemokines facilitate the
      clearance of invaders through the recruitment of leukocytes. Thus, upregulation
      of chemokine expression represents an important innate host defense response
      against invading microbes such as Streptococcus pneumoniae. In this study, we
      report that the expression of Monocyte Chemotactic Protein 1 (MCP1) was highly
      induced in response to S. pneumoniae in vitro and in vivo. Among numerous
      virulence factors, pneumococcal pneumolysin was found to be the major factor
      responsible for this induction. Furthermore, MCP1 induction was mediated by the
      p38 mitogen-activated protein kinase (MAPK) whose activation was controlled by
      MAPK phosphatase 1 (MKP1). Therefore, this study reveals novel roles of
      pneumolysin in mediating MKP1 expression for the regulation of MCP1 expression in
      human epithelial cells.

PMID- 20803087
TI  - A DnaJ-like homolog from Cryphonectria parasitica is not responsive to hypoviral
      infection but is important for fungal growth in both wild-type and hypovirulent
      strains.
AB  - A DnaJ-like gene, Cpdj1, a molecular chaperone and regulator of Hsp70 in
      Cryphonectria parasitica, was characterized. The protein product of Cpdj1 gene
      consists of 379 amino acids with a predicted molecular mass of 40.6 kDa and a pI
      of 7.79. The deduced protein sequence revealed preservation of the conserved hall
      mark J-region and exhibited high homolo y to all known DnaJ-like proteins.
      Disruption of the Cpdj1 gene resulted in slow growth and produced colonies
      characterized by retarded growth and deep orange color. Accordingly, reduced
      virulence of the Cpdj1-null mutant was observed. This reduced growth rate was
      magnified when the Cpdj1-null mutant was cultured under heat-stress conditions.
      Reduced conidiation was also observed in the Cpdj1-null mutant, indicating that
      Cpdj1 gene, although not essential for cell viability, is required for
      appropriate cellular processes including growth and sporulation. Northern
      analysis showed that Cpdj1 was constitutively expressed, and when the culture was
      subject to high temperature, a strong induction of the transcript was observed.
      No significant difference in the expression and induction pattern of Cpdj1 was
      observed between virus-free EP155/2 and virus-infected hypovirulent UEP1 strains.
      However, further severe defects in mycelia growth and conidiation were observed
      in the hypovirus-infected Cpdj1-null mutant suggesting that the presence of Cpdj1
      is required for mycelia growth and sporulation of the hypovirus-infected strain.

PMID- 20803088
TI  - Characterization of the residues of alphaX I-domain and ICAM-1 mediating their
      interactions.
AB  - Integrin alphaXbeta2 performs a significant role in leukocyte functions including
      phagocytosis and migration, and binds to a variety of ligands, including
      fibrinogen, iC3b, and ICAM-1. A particular domain of the alpha subunit of the
      integrin - the alphaX I-domain - is a ligand binding site, and the interaction of
      the alphaX I-domain and ICAM-1 on the endothelium is an important step in
      leukocyte extravasation. In order to elucidate the structural aspects of this
      interaction, we defined the moieties of the alphaX and ICAM-1 relevant to their
      interaction in this study. It was determined that the ICAM-1 binding sites of the
      alphaX I-domain were located in the alpha3alpha4, betaDalpha5, and betaFalpha7
      loops at the top surface of the I-domain. The residues Q(202), K(242), K(243),
      E(298) and D(299) on these loops were crucial for the recognition of ICAM-1.
      Among these residues, K(242) and K(243) on the betaDalpha5 loop were found to be
      the most salient, thereby suggesting an ionic interaction between these proteins.
      Domain 3 of ICAM-1 was identified as a primary binding site for the alphaX I
      domain. Two regions of domain 3 (D(229)QRLNPTV and E(254)DEGTQRL) perform
      critical functions in the binding of the alphaX I-domain. Especially, the residue
      E(254)DEG, is most important with regard to the alphaX I-domain.

PMID- 20803089
TI  - High fat diet altered the mechanism of energy homeostasis induced by nicotine and
      withdrawal in C57BL/6 mice.
AB  - Nicotine treatment has known to produce an inverse relationship between body
      weight and food intake in rodents. Present study determined the effect of
      repeated treatment with nicotine and withdrawal in control and obese mice, on:
      (1) body weight, caloric intake and energy expenditure; (2) hypothalamic
      neuropeptides mRNA expression; and (3) serum leptin. 21-week-old C57BL/6 mice (n
      = 65) received nicotine (3.0 mg/kg/day; 2 weeks) and saline (1 ml/kg/day; 2
      weeks) subcutaneously. Animals were given either a normal-fat (10% kcal from fat,
      NF) or a high-fat diet (45% kcal from fat, HF) from the 12th week to 25th week.
      While, nicotine treatment for 14 days induced an increase in hypothalamic agouti
      related protein, cocaine- and amphetamine- regulated transcript, pro
      opiomelanocortin mRNA expressions, nicotine also produced a reducing effect in
      body weight gain and leptin concentration in NF mice. High-fat diet induced obese
      mice showed a blunted hypothalamic and leptin response to nicotine. Remarkable
      weight loss in obese mice was mediated not just by decreasing caloric intake, but
      also by increasing total energy expenditure (EE). During nicotine withdrawal
      period, weight gain occurred in NF and HF groups, which was ascribed to a
      decrease in EE rather than changes in caloric intake. Hypothalamic AgRP might
      play a role for maintaining energy balance under the nicotine-induced negative
      energy status.

PMID- 20803090
TI  - Transcription factor 7-like 2 (TCF7L2) regulates activin receptor-like kinase 1
      (ALK1)/Smad1 pathway for development of diabetic nephropathy.
AB  - Smad1 has previously been shown to play a key role in the development of diabetic
      nephropathy (DN), by increasing synthesis of extracellular matrix. However, the
      regulatory mechanism of Smad1 in DN is still unclear. This study aims to
      elucidate molecular interactions between activin receptor-like kinase 1
      (ALK1)/Smad1 signaling pathway and transcription factor 7-like 2 (TCF7L2) in the
      progression of DN in vitro and in vivo. The expressions of TCF7L2 and ALK1 were
      induced by advanced glycation end products (AGEs) in parallel with Smad1,
      phosphorylated Smad1 (pSmad1), and alpha-smooth muscle actin (alpha-SMA) through
      TGF-beta1 in cultured mesangial cells. Constitutively active ALK1 increased
      pSmad1 and alpha-SMA expressions. The binding of TCF7L2 to ALK1 promoter was
      confirmed by chromatin immunoprecipitation assay. Furthermore, TCF7L2 induced
      promoter activity of ALK1. AGEs and TGF-beta1 induced a marked increase in TCF7L2
      expression in parallel with ALK1. Overexpression of TCF7L2 increased the
      expressions of ALK1 and Smad1. Inversely, TCF7L2 knockdown by siRNA suppressed
      alpha-SMA expression as well as ALK1 and Smad1. The iNOS transgenic mice (iNOS
      Tgm), which developed diabetic glomerulosclerosis resembling human diabetic
      nephropathy, exhibited markedly increased expressions of ALK1, TCF7L2, Smad1,
      pSmad1, and alpha-SMA in glomeruli in association with mesangial matrix
      expansion. These results provide a new evidence that the TCF7L2/ALK1/Smad1
      pathway plays a key role in the development of DN.

PMID- 20803091
TI  - Alu-derived old world monkeys exonization event and experimental validation of
      the LEPR gene.
AB  - The leptin receptor (LEPR) is a crucial regulatory protein that interacts with
      Leptin. In our analysis of LEPR, novel AluJb-derived alternative transcripts were
      identified in the genome of the rhesus monkey. In order to investigate the
      occurrence of AluJb-derived alternative transcripts and the mechanism underlying
      exonization events, we conducted analyses using a number of primate genomic DNAs
      and adipose RNAs of tissue and primary cells derived from the crab-eating monkey.
      Our results demonstrate that the AluJb element has been integrated into our
      common ancestor genome prior to the divergence of simians and prosimians. The
      lineage-specific exonization event of the LEPR gene in chimpanzees, orangutans,
      and Old World monkeys appear to have been accomplished via transition mutations
      of the 5' splicing site (second position of C to T). However, in New World
      monkeys and prosimians, the AluJb-related LEPR transcript should be silenced by
      the additional transversion mutation (fourth position of T to G). The AluJb
      related transcript of human LEPR should also be silenced by a mutation of the 5'
      splicing site (first position of G to A) and the insertion of one nucleotide
      sequence (minus fourth position of A). Our data suggests that lineage-specific
      exonization events should be determined by the combination event of the formation
      of splicing sites and protection against site-specific mutation pressures. These
      evolutionary mechanisms could be major sources for primate diversification.

PMID- 20803092
TI  - Inhibiting N-cadherin-mediated adhesion affects gap junction communication in
      isolated rat hearts.
AB  - Cadherin-mediated adherens junctions is impaired concomitant with a decrease in
      connexin 43 (Cx43) in diseases or pathological processes. We have investigated
      the acute effects of adherens junction impairment in isolated rat hearts by
      introducing Ala-His-Ala-Val-Asp-NH(2) (AHAVD, a synthetic peptide) as a specific
      inhibitor of N-cadherin. Effect of AHAVD on N-cadherin mediated adhension was
      analyzed by Cardiomy-ocyte aggregation assay. Laser confocal microscopy showed
      disrupted cell-cell contacts in cultured neonatal cardiomyocytes co-incubated
      with 0.2 mM AHAVD. In isolated adult rat hearts, Cx43 was redistributed along the
      bilateral of cardiomyocytes from the intercalated discs and significant
      dephosphorylation of Cx43 on serine368 occurred concomitantly with decreased gap
      junction (GJ) function in dose dependent manner after 1 h perfusion with AHAVD.
      These results indicate that impairing cad-herin-mediated adhesion by AHAVD
      rapidly results in Cx43 redistribution and dephosphorylation of serine368,
      thereby impairing GJ communication function.

PMID- 20803093
TI  - Interaction of T-type calcium channel Ca(V)3.3 with the beta-subunit.
AB  - The beta-subunit of high-voltage-activated (HVA) calcium channels is essential
      for the regulation of expression and gating. On the other hand, various reports
      have suggested that beta subunits play no role in the regulation of low-voltage
      activated T-type channels. In addition there has been no clear demonstration of a
      physical interaction between the alpha-subunit of T-type channel with beta
      subunit. In this study, we systematically investigated the interaction between
      Ca(V)alpha and Ca(V)beta. The four Ca(V)beta isoforms were expressed in a
      bacterial system and purified into homogeneity, whereas the ten types of
      Ca(V)alpha alpha interaction domain (AID) peptides were chemically synthesized.
      All possible combinations of Ca(V)alpha and Ca(V)beta were then tested for by in
      vitro immunoassays. We describe here the identification of a new interaction
      between Ca(V)3.3 and Ca(V)beta proteins. This interaction is of low affinity
      compared to that between the AID of the HVA alpha-subunit and the alpha-binding
      pocket (ABP) site of the beta-subunit. The AID peptide of HVA channel exerted no
      effect on the Ca(V)3.3-Ca(V)beta interaction, thus demonstrating that another
      site not in the ABP of Ca(V)beta protein played a role in binding with Ca(V)3.3.
      This is the first demonstration of an alpha-beta subunit interaction in a T-type
      calcium channel.

PMID- 20803094
TI  - Epidemiological transition and the double burden of disease in Accra, Ghana.
AB  - It has long been recognized that as societies modernize, they experience
      significant changes in their patterns of health and disease. Despite rapid
      modernization across the globe, there are relatively few detailed case studies of
      changes in health and disease within specific countries especially for sub
      Saharan African countries. This paper presents evidence to illustrate the nature
      and speed of the epidemiological transition in Accra, Ghana's capital city. As
      the most urbanized and modernized Ghanaian city, and as the national center of
      multidisciplinary research since becoming state capital in 1877, Accra
      constitutes an important case study for understanding the epidemiological
      transition in African cities. We review multidisciplinary research on culture,
      development, health, and disease in Accra since the late nineteenth century, as
      well as relevant work on Ghana's socio-economic and demographic changes and
      burden of chronic disease. Our review indicates that the epidemiological
      transition in Accra reflects a protracted polarized model. A "protracted" double
      burden of infectious and chronic disease constitutes major causes of morbidity
      and mortality. This double burden is polarized across social class. While wealthy
      communities experience higher risk of chronic diseases, poor communities
      experience higher risk of infectious diseases and a double burden of infectious
      and chronic diseases. Urbanization, urban poverty and globalization are key
      factors in the transition. We explore the structures and processes of these
      factors and consider the implications for the epidemiological transition in other
      African cities.

PMID- 20803095
TI  - Firearm retailers' willingness to participate in an illegal gun purchase.
AB  - Firearm-related violence is a significant public health and public safety problem
      for cities in the USA, and licensed firearm retailers are an important source of
      the guns used in that violence. Using a scripted telephone interview, we screened
      a sample of licensed retailers in California to assess their willingness to
      participate in the surrogate or "straw" purchase of a handgun; such purchases are
      illegal under federal law. Of 149 retailers who provided a response, 30 (20.1%)
      agreed to participate. In multivariate analysis, pawnbrokers were more likely to
      agree than were gun dealers (odds ratio 6.58, 95% confidence interval 1.99
      21.71). Sales of handguns that were later subjected to ownership tracing (a proxy
      measure for a gun's use in crime) were not more frequent among retailers who
      agreed to participate than among others, and other findings were unexpected as
      well.

PMID- 20803096
TI  - The fighter.
AB  - In this true story, an Eritrean man's wife rapidly becomes unconscious, and he
      tenaciously pursues a diagnosis and procures treatment. His personal struggle,
      juxtaposed with reflection on Eritrea's 30-year fight for independence from
      Ethiopia, highlights the power of persistence in the face of some of the most
      adverse conditions in the world.

PMID- 20803097
TI  - Bariatric surgery reverses natural killer (NK) cell activity and NK-related
      cytokine synthesis impairment induced by morbid obesity.
AB  - BACKGROUND: Obesity is related to a higher rate of infections and some types of
      cancer. Here we analyzed the impact of obesity and weight loss induced by Roux-en
      Y gastric bypass (RYGB) on immunological parameters, i.e., cytokine productions
      and natural killer cell function. METHODS: We analyzed 28 morbidly obese patients
      before and 6 months after RYGB. Biochemical parameters were analyzed in plasma.
      The percent of natural killer (NK) cells, their cytotoxicity, and the production
      of cytokines by peripheral blood mononuclear cells were analyzed. The percent of
      NK cells was determined by flow cytometry and cytokine production determined by
      enzyme-linked immunosorbent assay. NK cytotoxicity was determined by the lactate
      dehydrogenase release assay. RESULTS: The weight loss 6 months following surgery
      was 35.3 +/- 4.5 kg. RYGB also improves biochemical parameters. No significant
      difference was found in the percent of NK cells after surgery. We found an
      increase in the production of interferon-gamma, interleukin (IL)-12 and IL-18,
      but not in IL-2, 6 months after RYGB. Cytotoxic activity of NK cells was
      significantly enhanced 6 months after RYGB [17.1 +/- 14.7% before RYGB vs 51.8 +/
      11.3% at 6 months after, at 40:1 effector to target cell ratio; p < 0.001]. We
      observed significant post-surgical improvement in the cytotoxic activity curve in
      22 out of 28 patients (78.6%), irrespective of the target to effector cell ratio.
      CONCLUSIONS: The weight loss induced by RYGB modifies the production of cytokines
      related with NK cell function and improves its activity.

PMID- 20803098
TI  - Early changes in incretin secretion after laparoscopic duodenal-jejunal bypass
      surgery in type 2 diabetic patients.
AB  - BACKGROUND: A stomach-preserving duodenal-jejunal bypass (DJB) has been used for
      the treatment of type 2 diabetes mellitus (DM) since Rubino et al. first reported
      a prospective trial. However, there has been no report on changes in incretin
      secretion after DJB. We aimed to investigate whether DJB changes incretin
      secretion in nonmorbidly obese type 2 diabetic patients. METHODS: The inclusion
      criteria in this prospective study were: patient age of 20-65 years, body mass
      index of <30 kg/m(2), a history of type 2 DM for <=10 years, and fasting C
      peptide >=0.3 nmol/l. Six patients with type 2 DM without morbid obesity
      underwent DJB. Fasting plasma glucose and glycated hemoglobin (HbA1c) were
      measured. An oral glucose tolerance test (OGTT) was performed with measurement of
      glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP),
      insulin, C-peptide, and glucagon. The study subjects were followed up for 6
      months. RESULTS: The body weight of patients declined after surgery. The area
      under the curve (AUC) of glucose, peak glucose levels during OGTT, and HbA1c also
      declined until 3 months postoperatively. The AUC of C-peptide and insulin tended
      to increase postoperatively. The AUC of glucagon had a significant increase at 6
      months postoperatively. The AUC of active GLP-1 increased at 1 month and at 6
      months postoperatively. There was no change in the AUC of total GIP. CONCLUSION:
      Our data suggest that DJB increases GLP-1 secretion in nonmorbidly obese type 2
      diabetic patients. However, long-term data are needed to confirm this finding.

PMID- 20803099
TI  - Changes in proteomic features induced by insulin on vascular smooth muscle cells
      from spontaneous hypertensive rats in vitro.
AB  - Hyperinsulinemia is a risk factor in atherosclerosis formation that it stimulated
      vascular smooth muscle cells (VSMCs) proliferation and migration. To understand
      the underlying molecular mechanism involved in the processes of cellular response
      to insulin, VSMCs from Wistar-Kyoto rat (WKY) and spontaneous hypertensive rat
      (SHR) were isolated and cultured, and its proteome was comparatively analyzed
      with normal control by two-dimensional gel electrophoresis (2-DE). Results showed
      that the proliferation of VSMCs from SHR be more sensitive to insulin stimulation
      than that VSMCs from WKY. The detectable spots ranged from 537 to 608 on the gels
      in VSMCs of SHR, and 413 +/- 31 spots in VSMCs of WKY. The different expressed
      protein spots in VSMCs of SHR were then isolated and measured by matrix-assisted
      desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). A total of
      18 spots showed a sharp clear spectrum, and 13 spots matched with the known
      proteins from database. These proteins were mainly involved in cytoskeleton,
      glycometabolism, and post-translational processes. Among these proteins, OPN and
      matrix gla protein were up-regulated expression proteins, while alpha-SM actin
      was down-regulated. Furthermore, these preliminarily identified proteins
      confirmed by RT-PCR and western blotting analysis were coincident with the
      changes in 2-DE check. In addition, the cytoskeleton changes and migration rate
      of VSMCs from SHR treated by insulin increased significantly. The results showed
      that insulin plays a crucial role in activating proliferation and migration of
      VSMCs, by regulating the phenotype switch of VSMCs.

PMID- 20803100
TI  - Functional annotation of Fibrobacter succinogenes S85 carbohydrate active
      enzymes.
AB  - Fibrobacter succinogenes is a cellulolytic bacterium that degrades plant cell
      wall biomass in ruminant animals and is among the most rapidly fibrolytic of all
      mesophilic bacteria. The complete genome sequence of Fisuc was completed by the
      DOE Joint Genome Institute in late 2009. Using new expression tools developed at
      Lucigen and C5-6 Technologies and a multi-substrate screen, 5,760 random shotgun
      expression clones were screened for biomass-degrading enzymes, representing 2*
      genome expression coverage. From the screen, 169 positive hits were recorded and
      33 were unambiguously identified by sequence analysis of the inserts as belonging
      to CAZy family genes. Eliminating duplicates, 24 unique CAZy genes were found by
      functional screening. Several previously uncharacterized enzymes were discovered
      using this approach and a number of potentially mis-annotated enzymes were
      functionally characterized. To complement this approach, a high-throughput system
      was developed to clone and express all the annotated glycosyl hydrolases and
      carbohydrate esterases in the genome. Using this method, six previously described
      and five novel CAZy enzymes were cloned, expressed, and purified in milligram
      quantities.

PMID- 20803101
TI  - Chemoradiation for unresectable gall bladder cancer: time to review historic
      nihilism?
AB  - PURPOSE: Treatment of unresectable locally advanced gallbladder cancers (LAGBC)
      usually consists of various palliative strategies which provide only a modest
      survival benefit. Here, we present a series of three patients of LAGBC-treated
      consecutively at our center with preoperative chemoradiation using tomotherapy
      and concurrent gemcitabine. METHODS: All three cases were reported to be
      adenocarcinoma by biopsy or fine-needle aspiration cytology. All the patients
      underwent positron emission tomography with computerized tomography scan to rule
      out distant metastasis and also to map the extent of disease for radiotherapy
      planning. Preoperative chemoradiation consisted of gemcitabine at 300 mg/m(2)
      weekly and tomotherapy with daily image guidance with MVCT over 5 weeks to a dose
      of 57 Gy in 25 fractions to the gross tumor and 45 Gy in 25 fractions to the
      clinical target volume to cover the areas of microscopic spread. RESULTS:
      Complete metabolic and radiologic response was observed for 2 patients and
      partial response for 1 patient. Two patients underwent complete surgical excision
      of which 1 patient had complete pathological response and 1 patient had small
      residual tumor at the primary and no nodal metastasis. The third patient could
      not undergo surgery due to medical reasons. CONCLUSIONS: The clinical outcome for
      unresectable LAGBC with preoperative chemoradiation in terms of feasibility,
      safety, and survival is encouraging. This treatment strategy has a curative
      potential for the otherwise fatal disease.

PMID- 20803102
TI  - Musa genetic diversity revealed by SRAP and AFLP.
AB  - The sequence-related amplified polymorphism (SRAP) technique, aimed for the
      amplification of open reading frames (ORFs), vis-a-vis that of the amplified
      fragment length polymorphisms (AFLP) were used to analyze the genetic variation
      and relationships among forty Musa accessions; which include commercial cultivars
      and wild species of interest for the genetic enhancement of Musa. A total of 403
      SRAP and 837 AFLP amplicons were generated by 10 SRAP and 15 AFLP primer
      combinations, of which 353 and 787 bands were polymorphic, respectively. Both
      cluster analysis of unweighted pair-grouping method with arithmetic averages
      (UPGMA) and principal coordinate (PCO) analysis separated the forty accessions
      into their recognized sections (Eumusa, Australimusa, Callimusa and Rhodochlamys)
      and species. The percentage of polymorphism amongst sections and species and the
      relationships within Eumusa species and subspecies varied between the two marker
      systems. In addition to its practical simplicity, SRAP exhibited approximately
      threefold more specific and unique bands than AFLP, 37 and 13%, respectively.
      SRAP markers are demonstrated here to be proficient tools for discriminating
      amongst M. acuminata, M. balbisiana and M. schizocarpa in the Eumusa section, as
      well as between plantains and cooking bananas within triploid cultivars.

PMID- 20803103
TI  - Anti-tumour efficacy of mitofusin-2 in urinary bladder carcinoma.
AB  - Mitochondrial GTPase mitofusin-2 gene (Mfn2) is a novel gene characterised as a
      cell proliferation inhibitor. Mfn2 protein over-expression, mediated by an
      adenovirus, has a significant anti-tumour effect in A548 and HT-29 cells.
      However, there is no report on the effect of Mfn2 on urinary bladder carcinoma
      (UBCC). In this study, we sought to investigate the function of Mfn2 in UBCC.
      Mfn2 expression in 36 paired UBCC samples was investigated by reverse
      transcription-polymerase chain reaction and Western blot analyses. An adenovirus
      encoding the complete Mfn2 open reading frame (Ad-Mfn2) was used to infect UBCC
      cells, and an adenoviral vector encoding green fluorescent protein (Ad-GFP) was
      used as a control. The effects of Mfn2 on cell-cycle distribution and apoptosis
      were assessed by flow cytometry and Western blot analyses. The Mfn2 protein
      showed significantly lower expression in UBCC tissues than nearby non-tumourous
      tissues. Ad-Mfn2 exhibited a significant anti-tumour effect in T24 and 5,637
      cells. Mfn2 overexpression in T24 cells significantly inhibited cell
      proliferation, by arresting the transition of the cell cycle from the G(1) to S
      phase, and induced apoptosis by upregulating active caspase-3 and cleaved PARP
      levels. Mfn2 also induced increased p21 and p27 expression levels, but down
      regulated PCNA levels. These findings indicate that Mfn2 is a potential UBCC
      tumour suppressor gene, which showed significantly lower expression in tumour
      tissues than adjacent non-tumourous tissues and could promote apoptosis and
      inhibit the proliferation of UBCC cells. Mfn2 may become an important therapeutic
      target for treating UBCC.

PMID- 20803104
TI  - The diagnosis and management of syncope.
AB  - The European Society of Cardiology has recently revised its guidelines on the
      diagnosis and management of syncope. This article summarizes the recommendations
      of these guidelines, outlining the initial evaluation of transient loss of
      consciousness, risk stratification, diagnostic testing, and the recommended
      treatment for patients with syncope of various etiologies. Special points
      regarding the evaluation of syncope in children and the elderly are outlined, and
      the role of syncope management units in hospitals is discussed.

PMID- 20803105
TI  - Comparative biogeography of Chromobacterium from the neotropics.
AB  - The genus Chromobacterium encompasses free-living Gram-negative bacteria. Until
      2007, the genus consisted of only one species but six species are now recognized.
      Chromobacterium violaceum is the type species of the genus and is commonly found
      in soil and water in tropical and sub-tropical regions. We have investigated a
      collection of 111 isolates displaying violet pigmentation from undisturbed
      aquatic and soil environments from Brazilian Cerrado ecosystem. The 16S rRNA gene
      phylogeny revealed that all isolates were allocated in a monophyletic cluster
      inside the Chromobacterium genus and formed few clusters related most closely
      with Chromobacterium piscinae. The two sets of isolates from water and soil were
      analyzed by the repetitive extragenic palindromic (rep)-PCR genomic
      fingerprinting technique using a BOX-AR1 primer. The antimicrobial susceptibility
      and the different carbon sources utilized by these isolates were also
      investigated. Physiological profiles of the isolates generated by BIOLOG GN2
      plates showed great versatility in the substrate utilization, much higher than
      the C. violaceum ATCC 12472. All isolates exhibited a high minimum inhibitory
      concentration (MIC) to ampicillin (MIC > 512 MUg/ml) and were inhibited by
      ciprofloxacin, tetracycline and mercury at the lowest concentration tested (MIC <
      2 MUg/ml). Thirteen BOX-PCR band patterns were identified from 33 individual
      fingerprints. Eleven patterns provided evidence for endemic distributions.
      Antimicrobial susceptibility and BOX-PCR fingerprint clustering showed a clear
      distinction between Chromobacterium isolates from the water and soil. The results
      suggested that microenvironment barriers such as water and soil can play an
      important role in the periodic selection and diversification of Chromobacterium
      population ecotypes.

PMID- 20803106
TI  - Optimization of bioethanol production during simultaneous saccharification and
      fermentation in very high-gravity cassava mash.
AB  - Hydrolysis and fermentation conditions for production of ethanol from very high
      gravity cassava mash by Saccharomyces cerevisiae during simultaneous
      saccharification and fermentation (SSF) processing were optimized using a
      statistical methodology. During the first part of the study, Placket-Burman
      design (PBD) was used to study 19 factors that could potentially influence
      ethanol production. Gravity, particle size, initial pH, and fermentation
      temperature were identified as key factors that significantly increased final
      ethanol concentration. The main and interaction effects of these factors were
      subsequently evaluated based on a quadratic equation generated by central
      composite design (CCD) using response-surface methodology (RSM). Under the
      optimized very high-gravity conditions, the final ethanol concentration obtained
      from experiment increased from 8.21% (wt.%) to 15.03% (wt.%) and was in good
      agreement with model prediction. By employing two other commercial Saccharomyces
      strains, similar results were obtained under the same optimized condition.
      Therefore, we conclude that final ethanol concentration, ethanol productivity (V
      (P/max)), glucose utilization (Y (G/s), Y (P/s)), and fermentation efficiency
      (eta (f)) were enhanced or maintained under the optimized condition of 40%
      gravity, 390 MUm particle size, initial pH 5.5, and 27 degrees C fermentation
      temperature.

PMID- 20803107
TI  - Orbital inflammatory pseudotumors: etiology, differential diagnosis, and
      management.
AB  - Orbital inflammation is typically an idiopathic process that occasionally may be
      identified with a specific local or systemic disease as the causative agent.
      Orbital inflammatory pseudotumor (also known as idiopathic orbital inflammation
      syndrome, orbital pseudotumor, nonspecific orbital inflammation, and orbital
      inflammatory syndrome) is defined as an idiopathic tumor-like inflammation
      consisting of a pleomorphic cellular response and a fibrovascular tissue
      reaction. Various rheumatologic disorders are associated with orbital
      inflammation and must be ruled out in cases of orbital inflammatory pseudotumor,
      including Wegener's granulomatosis, giant cell arteritis, systemic lupus
      erythematosus, dermatomyositis, and rheumatoid arthritis. The mainstay of therapy
      is corticosteroid therapy, although there is an increasing trend toward use of
      antimetabolites, alkylating agents, cytotoxic agents, and other immunosuppressive
      agents.

PMID- 20803108
TI  - Current treatment strategy of diffuse large B-cell lymphomas.
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma,
      accounting for approximately 25-30% of all new patients. Rituximab, a genetically
      engineered chimeric monoclonal antibody that specifically binds to CD20, is the
      first monoclonal antibody approved for the treatment of B-cell lymphoma.
      Rituximab significantly improves treatment outcome in DLBCL. A large-phase III
      study demonstrated improved overall survival (OS) in patients with DLBCL treated
      with R-CHOP therapy. The Groupe d'Etude des Lymphomes de l'Adulte (GELA), Eastern
      Cooperative Oncology Group (ECOG) and German High-Grade Non-Hodgkin Lymphoma
      Study Group (DSHNHL) studies designed for patients older than 60 years have
      clearly shown prolonged event-free survival (EFS) and OS among patients who
      received rituximab and chemotherapy. For patients under 60 years, the MabThera
      International Trial Group (MInT) study demonstrated improved EFS and OS after the
      addition of rituximab to CHOP therapy. However, the R-CHOP therapy does not
      provide a satisfactory treatment outcome in the high-risk group according to the
      international prognostic index. Therefore, R-CHOP therapy is the new standard
      therapy in elderly and young, low-risk DLBCL patients. For young, high-risk DLBCL
      patients, treatment that incorporates rituximab and hematopoietic stem cell
      transplantation has been administered in clinical studies.

PMID- 20803109
TI  - Teaching residents out-of-hospital anesthesia-what are we waiting for?

PMID- 20803110
TI  - Continuous local anesthetic infusion through ultrasound-guided rectus sheath
      catheters.

PMID- 20803111
TI  - Report on the computer software contest at the 39th Congress of the Lapan Society
      of Anesthesiology.
AB  - We held another computer software contest at the 39th Congress of the JSA. The
      aim and procedure were similar to those for the first contest in 1991. Twenty
      four softwares entered the contest; the machines are divided approximately two to
      one ratio between NEC PC9801 series and Macintosh. We received donations of 2
      million yen worth of instruments and goods for prizes plus some cash. They were
      given away to those who made entries for the contest.Most of these programs have
      been registered as free softwares at various computer networks. A plan is under
      way to distribute them in diskette forms.

PMID- 20803113
TI  - Beneficial effects of the dietary flavonoid quercetin.

PMID- 20803114
TI  - Cytotoxic 10-(indol-3-yl)-[13]cytochalasans from the fungus Chaetomium elatum
      ChE01.
AB  - Nine 10-(indol-3-yl)-[13]cytochalasans such as a new chaetoglobosin V (1); two
      new natural products, prochaetoglobosin III (2) and prochaetoglobosin III(ed)
      (3); six known chaetoglobosins B-D (4-6), F (7), and G (8) and isochaetoglobosin
      D (9) in addition to two known sterols, 24(R)-5alpha,8alpha-epidioxyergosta-6-22
      diene-3beta-ol (10) and ergosterol (11), were isolated from the fungus Chaetomium
      elatum ChE01. The structures of these compounds were elucidated by spectroscopic
      methods. Compounds 1-9 showed cytotoxicity against the human breast cancer
      (IC(50) 2.54-21.29 microM) and cholangiocarcinoma cell lines (IC(50) 3.41-86.95
      microM).

PMID- 20803115
TI  - Baimantuoluosides D-G, four new withanolide glucosides from the flower of Datura
      metel L.
AB  - In our search for bioactive anti-psoriasis compounds from the flower of Datura
      metel L, we isolated four new withanolide glucosides, baimantuoluosides D, E, F
      and G (1-4). The structures of the new compounds are (5alpha,6alpha,7beta,22R)
      5,6,7,27-tetrahydroxy-1-oxowitha-2,24-dien-27-O-beta-D-glucopyranoside (1),
      (5alpha,6beta,7alpha,22R)-5,6,7,27-tetrahydroxy-1-oxowitha-2,24-dien-27-O-beta-D
      glucopyranoside (2), (5alpha,6beta,7alpha,12beta,22R)-5,6,7,12,27-pentahydroxy-1
      oxowitha-2,24-dien-27-O-beta-D-glucopyranoside (3), and (5alpha,6beta,22R)-5,6,27
      trihydroxy-1-oxowitha-2,24-dien-27-O-beta-D-glucopyranoside (4) on the basis of
      chemical and physicochemical evidence.

PMID- 20803116
TI  - Comparative analysis of the anti-inflammatory activity of Huang-lian extracts in
      lipopolysaccharide-stimulated RAW264.7 murine macrophage-like cells using
      oligonucleotide microarrays.
AB  - In this study, we attempted to determine the anti-inflammatory activity of a
      medicinal plant huang-lian using gene expression profiles as an index. Huang-line
      extracts (CEXs) were prepared from seven different plant origins and compared for
      their chemical composition and biological activity. In order to achieve this,
      RAW264.7 cells were treated with CEXs in the absence or presence of LPS for 6 h,
      and the differential gene expression profiles were analyzed using oligonucleotide
      microarrays. The alkaloid content of CEXs was determined by high performance
      liquid chromatography analysis. Evaluation of anti-inflammatory activity of CEXs
      was by measuring a decrease in cytokines and nitric oxide production in LPS
      stimulated RAW264.7 cells. Hierarchical clustering analysis revealed that three
      CEXs from Coptis chinensis formed a cluster separate from the other four CEXs in
      LPS-stimulated cells, and were the most effective anti-inflammatoryagents. The
      extract prepared from Picrorrhiza kurrooa neither induced any changes in gene
      expression profiles nor possessed any anti-inflammatory activity. The extract
      from Jeffersonia dubia, which exhibited the highest cytotoxicity among the CEXs
      tested, was most effective in suppressing LPS-induced nitric oxide production but
      was not able to inhibit proinflammatory cytokine production. The results obtained
      in this study demonstrate that overall gene expression profiles of the extracts
      correlated well with their biological activity and that CEXs prepared from plants
      of diverse origins vary in their biological activity. These data also suggest
      that gene expression profiles may serve as a good indicator for the
      pharmacological activities of medicinal plants arising from diverse origins.

PMID- 20803117
TI  - Two new dihydrofuranoisoflavanones from the leaves of Lespedeza maximowiczi and
      their inhibitory effect on the formation of advanced glycation end products.
AB  - Two new dihydrofuranoisoflavanones, 2',4',5-trihydroxy-[5''-(1,2-dihydroxy-1
      methylethyl)-dihydrofurano(2'',3'':7,8)]-(3S)-isoflavanone (1) and 2', 4', 5
      trihydroxy-[5''-(1,2-dihydroxy-1-methylethyl)-dihydrofurano(2'',3'':7,8)]-(3R)
      isoflavanone (2) as well as one already-known compound, (+)-catechin (3), were
      isolated from an n-BuOH soluble fraction from the leaves of Lespedeza
      maximowiczi. Spectroscopic data was used to elucidate the structures of compounds
      1 and 2. All of the isolates were evaluated in vitro for their inhibitory
      activity on the formation of advanced glycation end products (AGEs). Among these,
      compounds 1, 2, and 3 exhibited inhibitory activity against AGEs formation with
      IC(50) values of 20.6, 18.4, and 5.6 microM, respectively.

PMID- 20803118
TI  - A new isoflavone glycoside from the stem bark of Sophora japonica.
AB  - A new isoflavone glycoside, 6-methoxy-7-hydroxy-4'-O-beta-D-glucosyl isoflavone,
      glycitein-4'-O-beta-D-glucoside (10), along with nine known flavonoids, were
      isolated from the stem bark of Sophora japonica. The structures of these
      compounds were determined by analysis of spectroscopic data (1D -, 2D - NMR and
      HRMS). The inhibitory effects of all the isolated compounds on aldose reductase
      were evaluated in vitro. Among these compounds, daidzein (1), puerol A (4), and
      paratensein-7-O-glucoside (9) exhibited potent inhibitory effects, with IC(50)
      values of 3.2, 6.4, and 1.9 microM, respectively.

PMID- 20803119
TI  - Kaempferol glycosides and cardenolide glycosides, cytotoxic constituents from the
      seeds of Draba nemorosa (Brassicaceae).
AB  - Bioassay-directed fractionation of a methanolic extract from the seeds of Draba
      nemorosa (Brassicaceae) led to isolation of a new flavonol glycoside,
      drabanemoroside (5, kaempferol 3-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L
      arabinopyranose) along with four known flavonoid derivatives (1-4), four
      cardenolide glycosides (6-9). Kaempferol glycosides 2 and 5 showed strong
      cytotoxicity against human small lung cancer cell line A549 and melanoma SK-Mel-2
      with an IC(50) of 0.5 microg/mL and 1.9 microg/mL, respectively. Cardenolide
      glycosides 6-9 showed potent cytotoxicity (A549) in the range of 0.01-0.032
      microg/mL. Their structures were characterized based on spectroscopic data (2D
      NMR, HRTOFMS, IR, and UV) and comparison of literature values. The carbohydrate
      units were also confirmed by comparing the hydrolysate of 5 with authentic
      monosaccharides.

PMID- 20803120
TI  - Cytotoxic effects of triterpenoid saponins from Androsace umbellata against
      multidrug resistance (MDR) and non-MDR cells.
AB  - Cytotoxicity-guided fractionation and separation of MeOH extract from Androsace
      umbellata (Lour.) Merr. led to the isolation of four triterpenoid saponins.
      Compounds isolated from the n-BuOH soluble fraction were identified as
      saxifragifolin C (1), A (2), B (3), and D (4) by spectroscopic analysis.
      Antiproliferative effect of isolated compounds were evaluated by the
      sulforhodamin B assay against multidrug resistance (MDR; MES-SA/DX5 and
      HCT15/CLO2) and non-MDR (A549, SK-OV-3, SK-MEL-2, MES-SA, and HCT15) human tumor
      cell lines. All compounds exhibited strong cytotoxicity against non-MDR human
      tumor cell lines with IC(50) values of 0.19-2.37 muM. MDR cells and non-MDR cells
      had similar sensitivity to these compounds, however, MDR cells were highly
      resistant to doxorubicin. Compounds 1-4 induced an increase in the percentage of
      Annexin V-binding cells, indicating that 1-4 induced apoptosis in RAW 264.7
      cells. Also, the condensation of nuclei, a characteristic morphological change of
      apoptosis, was observed in RAW 264.7 cells by the treatment with n-BuOH fraction,
      compounds 3 and 4, respectively.

PMID- 20803121
TI  - Quercetin-mediated cell cycle arrest and apoptosis involving activation of a
      caspase cascade through the mitochondrial pathway in human breast cancer MCF-7
      cells.
AB  - Dietary polyphenols have been correlated with a reduced risk of developing
      cancer. Quercetin (a natural polyphenolic compound) induced apoptosis in many
      human cancer cell lines, including breast cancer MCF-7 cells. However, the
      involvement of possible signaling pathways and the roles of quercetin in
      apoptosis are still undefined. The purpose of this study was to investigate the
      effects of quercetin on the induction of the apoptotic pathway in human breast
      cancer MCF-7 cells. When MCF-7 cells were treated with quercetin for 24 and 48 h
      and at various doses (10-175 microM), cell viability decreased significantly in
      time- and dose-dependent manners. Exposure of MCF-7 cells to 10-175 microM
      quercetin resulted in an approximate 90.25% decrease in viable cells. To
      explicate the mechanism underlying the antiproliferative effect of quercetin,
      cell cycle distribution and apoptosis in MCF-7 cells was investigated after
      exposure to 150 microM quercetin for 6-48 h. Quercetin caused a remarkable
      increase in the number of S phase (14.56% to 61.35%) and sub-G1 phase cells (0.1%
      to 8.32%) in a dose- and time-dependent manner. Quercetin caused S phase arrest
      by decreasing the protein expression of CDK2, cyclins A and B while increasing
      the p53 and p57 proteins. Following incubation with quercetin for 48 h, MCF-7
      cells showed apoptotic cell death by the decreased levels of Bcl-2 protein and
      DeltaPsi(m) and increased activations of caspase-6, -8 and -9. Moreover,
      quercetin increased the AIF protein released from mitochondria to nuclei and the
      GADD153 protein translocation from endoplasmic reticulum to the nuclei. These
      data suggested that quercetin may induce apoptosis by direct activation of the
      caspase cascade through the mitochondrial pathway in MCF-7 cells.

PMID- 20803122
TI  - Preparation, characterization, and in vivo evaluation of mitoxantrone-loaded,
      folate-conjugated albumin nanoparticles.
AB  - Folic acid was covalently conjugated to bovine serum albumin nanoparticles
      (BSANP) to target the nanoparticles to SKOV3 cells expressing folate receptors.
      Mitoxantrone was incorporated into the folate-conjugated albumin nanoparticles,
      and the final nanoparticle size was 68 nm, as measured by a laser light
      scattering particle analyzer. The cytotoxic activity of mitoxantrone- loaded,
      folate-conjugated albumin nanoparticles (MTO-BSANP-folate), which was quantitated
      by (3)H-thymidine incorporation, was higher than mitoxantrone-loaded BSANP (MTO
      BSANP) and MTO solution, and could be inhibited by free folic acid. MTO
      BSANPfolate may be endocytosed via the folate receptor on the surface of SKOV3
      cells. MTO-BSANPfolate also inhibited tumor growth better than the MTO-BSANP and
      MTO solution in vivo. These results indicate that folate-conjugated BSANP may
      have therapeutic potential as a vector for anticancer drugs in cancer
      chemotherapy.

PMID- 20803123
TI  - Optimization of promethazine theoclate fast dissolving tablet using pore forming
      technology by 3-factor, 3-level response surface-full factorial design.
AB  - The present research work was undertaken to optimize and formulate Promethazine
      Theoclate as a fast dissolving tablet using pore forming technology that
      disintegrates or dissolves rapidly and offer a suitable approach for the
      treatment of nausea and vomiting. Fast dissolving tablets of Promethazine
      Theoclate was prepared by increasing the solubility i.e. using beta-cyclodextrin,
      crospovidone, and menthol. A 3(3) full factorial design was employed to
      investigate the combined influence of these three independent variables, i.e.,
      amount of menthol, crospovidone and beta-cyclodextrin on disintegration time,
      percentage friability and percentage drug release after 5 min. In the
      optimization study, multiple regression analysis has revealed that an optimum
      amount of menthol, crospovidone and beta-cyclodextrin gives a rapidly
      disintegrating/dissolving tablet. In order to prove the validity of the evolved
      mathematical model a checkpoint batch was also prepared. Optimized tablets were
      prepared with an optimum amount of beta-cyclodextrin, menthol and crospovidone
      which disintegrated in the 30 s, having friability 0.599% and released drug 89%
      after 5 min.

PMID- 20803124
TI  - Imperatorin sustained-release tablets: In vitro and pharmacokinetic studies.
AB  - We prepared and evaluated imperatorin (IMP) sustained-release tablets. IMP is an
      active compound in Angelica dahuricae, a Chinese herbal medicine. We used
      different polymers, such as hydroxypropyl methylcellulose (HPMC K4M, K15M, and
      K100M), carbopol 934P, sodium carboxymethyl cellulose (CMC-Na), and their
      combinations to prepare the matrix tablets and achieve the desired sustained
      release profile. The in vitro release profiles of these formulations were
      examined and fit to various kinetic release models. We also tested the effects of
      polymer combination ratios on the in vitro release rate. In vivo studies were
      performed for the optimized formulation in six beagle dogs, and pharmacokinetic
      parameters were compared with plain IMP tablets. IMP sustained-release tablets
      exhibited a more sustained plasma concentration than the plain tablets, with a
      relative bioavailability of 127.25%. The in vitro releases rates and in vivo
      absorption correlated for the initial 8 hours. These results demonstrate that the
      sustained-release tablet system can effectively control the release of IMP.

PMID- 20803125
TI  - Development of novel itraconazole-loaded solid dispersion without crystalline
      change with improved bioavailability.
AB  - To develop a novel itraconazole-loaded solid dispersion without crystalline
      change with improved bioavailability, various itraconazole-loaded solid
      dispersions were prepared with water, polyvinylpyrroline, poloxamer and citric
      acid. The effect of carriers on aqueous solubility of itraconazole was
      investigated. Their physicochemical properties were investigated using SEM, DSC,
      and powder X-ray diffraction. The dissolution, bioavailability in rats and
      stability of solid dispersions were evaluated. Unlike conventional solid
      dispersion system, the itraconazole-loaded solid dispersion with relatively rough
      surface did not change crystalline form of drug. Our DSC and powder X-ray
      diffraction results suggested that this solid dispersion was formed by attaching
      hydrophilic carriers to the surface of drug without crystal change, resulting in
      conversion of the hydrophobic drug to hydrophilic form. The itraconazole-loaded
      solid dispersion at the weight ratio of itraconazole/polyvinylpyrroline/poloxamer
      of 10/2/0.5 gave maximum drug solubility of about 20 microg/mL. It did not change
      the crystalline form of drug for at least 6 months, indicating that it was
      physically stable. It gave higher AUC, C(max) and T(max) compared to itraconazole
      powder and similar values to the commercial product, suggesting that it was
      bioequivalent to commercial product in rats. Thus, it would be useful to deliver
      a poorly water-soluble itraconazole without crystalline change with improved
      bioavailability.

PMID- 20803126
TI  - Differentiation of antlers from deer on different feeds using an NMR-based
      metabolomics approach.
AB  - Deer antler has been widely used as a dietary supplement for hundreds of years in
      Asian countries. The chemical composition of deer antlers strongly depends on the
      growth conditions of the deer, especially the feeds, but the effects of different
      feeds on deer antlers have not been studied. To expand our knowledge of the
      chemical constituents of deer antler and establish an efficient way of
      differentiating antlers obtained with different feeds, we applied an NMR-based
      metabolomics approach and OPLS-DA multivariate analysis. We show that the antlers
      from one species on two different feeds, made from grass or mulberry trees, can
      be reliably differentiated by our metabolomics approach. We identified chemical
      constituents of the deer antlers and the marker compounds that contribute to the
      difference between the feed groups. We also rigorously validated our
      differentiation approach by showing that it can correctly classify blind samples
      into their respective feed groups. Our approach is expected to help design feeds
      to produce antlers with more defined constituents, especially those with higher
      bioactivities.

PMID- 20803127
TI  - Improved pH-independent dissolution and oral absorption of valsartan via the
      preparation of solid dispersion.
AB  - This study aimed to improve the pH-independent solubility and dissolution
      characteristics of valsartan via the preparation of solid dispersions (SD) with
      poloxamer 407. SDs was prepared by using the solvent method at various drug
      polymer ratios and their dissolution characteristics were examined at different
      pHs. Oral pharmacokinetics of SDs was also evaluated in rats. Compared to the
      untreated powder, SDs significantly improved the dissolution rate as well as the
      extent of drug release at low pH. Particularly, SD having the drug-polymer ratio
      of 1:5 exhibited pH-independent dissolution of valsartan, resulting in the rapid
      and complete drug release over the pH range of 1.2 to 6.8. The improved
      dissolution of valsartan via SD formulation appeared to be well correlated with
      the enhanced oral exposure of valsartan in rats. SDs increased C(max) and AUC(0
      24) of valsartan by 2-7 folds in rats, implying that SDs should be effective to
      improve the bioavailability of valsartan. In conclusion, SDs containing poloxamer
      407 appeared to be effective to improve the pH-independent dissolution and oral
      absorption of valsartan.

PMID- 20803129
TI  - Wip1-expressing feeder cells retain pluripotency of co-cultured mouse embryonic
      stem cells under leukemia inhibitory factor-deprivated condition.
AB  - The optimization of in vitro culture conditions for embryonic stem cells (ESCs)
      is a matter of critical importance; a prompt supply of a sufficient population of
      cells that retain their pluripotency capabilities must be secured in order to
      make possible future cell therapies. Despite a number of reports asserting that a
      variety of cytokines, signaling ligands, and small molecules can help in
      maintaining the pluripotency of ESCs, mammalian feeder cells continue to be
      broadly accepted as the method of choice for ESC cultures. This appears to be
      because mammalian feeder cells seem to produce some as-yet-unidentified factor
      that makes them very effective as feeder cells. In this study, we investigated
      wild-type p53 inducible phosphatase (Wip1), the knockdown of which increases Wnt
      inhibitory factor-1 expression, in its feeder functions toward mouse embryonic
      stem cells, lowering the effect of Wnt, one of key signaling in maintaining
      stemness of ESCs. For this purpose, Wip1 was stably expressed in mouse embryonic
      fibroblast cell line (STO) using retro-viral gene delivery system and then the
      function as a feeder cell was monitored either with or without leukemia
      inhibitory factor (LIF) in culture medium. We demonstrated that mouse embryonic
      stem cells grown with Wip1 expressing STO showed higher alkaline phosphatase
      activity and sustained Oct-4 expression level even under LIF deprivation
      condition compared to both control and Wip1 phosphatase activity dead mutant
      expressing STO. These results imply that Wip1 phosphatase activity in feeder
      cells is important to retain pluripotency of mouse embryonic stem cells under LIF
      deprivation conditions. These results indicate that genetically engineered feeder
      cells such as Wip1 expressing cell lines, are alternative strategy for the
      optimization of maintenance and expansion of mouse embryonic stem cells.

PMID- 20803128
TI  - Cardioprotective effects of the novel Na+/H+ exchanger-1 inhibitor KR-32560 in a
      perfused rat heart model of global ischemia and reperfusion: Involvement of the
      Akt-GSK-3beta cell survival pathway and antioxidant enzyme.
AB  - To investigate the cardioprotective effects and mechanism of action of KR-32560
      {[5-(2-methoxy-5-fluorophenyl)furan-2-ylcarbonyl]guanidine}, a newly synthesized
      NHE-1 inhibitor, we evaluated the effects of KR-32560 on cardiac function in a
      rat model of ischemia/reperfusion (I/R)-induced heart injury as well as the role
      antioxidant enzymes and pro-survival proteins play these observed effects. In
      isolated rat hearts subjected to 25 min of global ischemia followed by 30 min of
      reperfusion, KR-32560 (3 and 10 microM) significantly reversed the I/Rinduced
      decrease in left ventricular developed pressure and increase in left ventricular
      enddiastolic pressure. In rat hearts reperfused for 30 min, KR-32560 (10 microM)
      significantly decreased the malondialdehyde content while increasing the
      activities of both glutathione peroxidase and catalase, two important antioxidant
      enzymes. Western blotting analysis of left ventricles subjected to I/R showed
      that KR-32560 significantly increased phosphorylation of both Akt and GSK-3beta
      in a dose-dependent manner, with no effect on the phosphorylation of eNOS. These
      results suggest that KR-32560 exerts potent cardioprotective effects against
      I/Rinduced rat heart injury and that its mechanism involves antioxidant enzymes
      and the Akt-GSK-3beta cell survival pathway.

PMID- 20803130
TI  - An experimental study of rabbit conjunctival epithelial toxicity using co
      treatment with mitomycin-C and a histone deacetylase inhibitor.
AB  - This study was conducted to evaluate cytotoxicity due to co-treatment with low
      dose Mitomycin-C (MMC) and the histone deacetylase inhibitor, suberoylanilide
      hydroxamic acid (SAHA) for glaucoma filtration surgery. In this study, the effect
      of co-treatment with MMC and SAHA to induce apoptosis in cultured conjunctival
      epithelial cells (CEs) in rabbit was investigated. The cytotoxic potential
      following co-treatment with MMC and SAHA in CEs via assay for reactive oxygen
      species (ROS) and lactate dehydrogenase (LDH) was also examined. Co-treatment
      with MMC and SAHA did not induce apoptosis in CEs. In addition, co-treatment with
      MMC and SAHA caused no significant alteration of ROS and LDH levels in CEs. This
      study therefore shows that low-dose MMC could still be used as an antimetabolite
      in co-treatment with SAHA to effectively inhibit fibrosis of Tenon's capsule
      fibroblasts (TCFs) following glaucoma filtration surgery, while minimizing
      cytotoxicity in CEs.

PMID- 20803131
TI  - Neuroprotective effects of constituents of the root bark of Dictamnus dasycarpus
      in mouse hippocampal cells.
AB  - Glutamate-induced oxidative injury causes neuronal degeneration related to many
      central nervous system diseases, such as Parkinson's disease, Alzheimer's
      disease, epilepsy and ischemia. The bioassay-guided fractionation of the EtOH
      extract of the root bark of Dictamnus dasycarpus Trucz. provided one
      neuroprotective limonoid, obacunone, together with a degraded limonoid,
      fraxinellone and two alkaloids, dictamine and haplopine. At concentrations of 100
      150 microM, obacunone showed the potent neuroprotective effects on
      glutamateinduced neurotoxicity and induced the expression of heme oxygenase (HO)
      1 in the mouse hippocampal HT22 cells. In addition, we found that obacunone
      increased p38 MAPK phosphorylation and induced HO-1 expression via p38 MAPK
      pathway. These results suggest that obacunone isolated from the root bark of D.
      dasycarpus increases cellular resistance to glutamate-induced oxidative injury in
      mouse hippocampal HT22 cells, presumably through the p38 MAPK pathway-dependent
      HO-1 expression. These results suggest that obacunone could be the effective
      candidates for the treatment of ROS-related neurological diseases.

PMID- 20803132
TI  - Preparation and evaluation of bioadhesive dibucaine gels for enhanced local
      anesthetic action.
AB  - In relieving local pains, dibucaine, one of ester type local anesthetics, has
      been used. In case of their application such as ointments and creams, it is
      difficult to expect their effects for a required period of time, because they are
      easily removed by wetting, movement and contacting. To develop suitable
      bioadhesive gels, the bioadhesive force of hydroxypropyl cellulose (HPC) was
      tested using auto-peeling tester. The effect of drug concentration on drug
      release was studied from the prepared 2% HPC-HF gels using synthetic cellulose
      membrane at 37 +/- 0.5 degrees C. We investigated the enhancing effects on drug
      permeation into skins, using some kind of enhancers such as the glycols, the non
      ionic surfactants, the fatty acids, and the propylene glycol derivatives.
      Anesthetic effects of dibucaine gels containing polyoxyethylene 2-oleyl ether
      were measured by tail flick analgesic meter. The bioadhesive force of various
      types of HPC such as GF, MF, and HF, was 0.0131, 0.0501, and 0.1346 N, at 2% HPC
      concentration, respectively. The HPC-HF gels showed the highest bioadhesive
      force. As the concentration of HPC-HF increased, the drug release increased. As
      the temperature increased, the drug release increased. Among the enhancers used,
      polyoxyethylene 2-oleyl ether showed the highest enhancing effects. According to
      the rat tail flick test, 1% drug gels containing polyoxyethylene 2-oleyl ether
      showed the prolonged local anesthetic effects. In conclusion, the dibucaine gel
      containing penetration enhancer and vasoconstrictor showing enhanced local
      anesthetic action could be developed by using the bioadhesive polymer, HPC.

PMID- 20803133
TI  - Expression, crystallization, and preliminary X-ray crystallographic analysis of
      putative SpoVG from Staphylococcus aureus.
AB  - SpoVG, originally identified in spore-forming Bacillus subtilis was known to be
      involved in spore formation of B. subtilis stationary phase cells at stage V.
      Later, close homologues of SpoVG of B. subtilis are shown to be present in the
      genomes of several nonsporulating bacteria as well. Especially in Staphylococcus
      aureus, SpoVG is speculated to be the major factor of the yabJ-spoVG operon
      required for capsule formation and methicillin and glycopeptides resistance. The
      putative SpoVG from S. aureus, a homodimeric protein consisting of two identical
      100-residue subunits, has been overexpressed in Escherichia coli with a C
      terminal purification tag and crystallized at 293 K using a precipitant solution
      consisting of 1.9 M (NH(4))(2)SO(4), 100 mM Tris-HCl, pH 7.5. X-ray diffraction
      data were collected to 3.10 A at 100 K. The crystals belong to the primitive
      tetragonal space group P41 (or P4(3)), with unit cell parameters of a = b =
      92.239, c = 98.588 A, alpha = beta = gamma = 90 degrees. Two dimers are present
      in the crystallographic asymmetric unit, with a calculated crystal volume per
      protein weight (V(M)) of 4.37 A(3)Da(-1) and a solvent content of 71.9%.

PMID- 20803134
TI  - QTL mapping of internal heat necrosis in tetraploid potato.
AB  - Internal heat necrosis (IHN) is a physiological disorder of potato tubers. We
      developed a linkage map of tetraploid potato using AFLP and SSR markers, and
      mapped QTL for mean severity and percent incidence of IHN. Phenotypic data
      indicated that the distribution of IHN is skewed toward resistance. Late foliage
      maturity was slightly but significantly correlated with increased IHN symptoms.
      The linkage map for 'Atlantic', the IHN-susceptible parent, covered 1034.4 cM and
      included 13 linkage groups, and the map for B1829-5, the IHN-resistant parent,
      covered 940.2 cM and contained 14 linkage groups. QTL for increased resistance to
      IHN were located on chromosomes IV, V, and groups VII and X of 'Atlantic', and on
      group VII of B1829-5 in at least 2 of 3 years. The QTL explained between 4.5 and
      29.4% of the variation for mean severity, and from 3.7 to 14.5% of the variation
      for percent incidence. Most QTL detected were dominant, and associated with
      decreased IHN symptoms. One SSR and 13 AFLP markers that were linked to IHN were
      tested in a second population. One AFLP marker was associated with decreased
      symptoms in both populations. The SSR marker was not associated with IHN in the
      second population, but was closely linked in repulsion to another marker that was
      associated with IHN, and had the same (negative) effect on the trait as the SSR
      marker did in the first population. The correlation between maturity and IHN may
      be partially explained by the presence of markers on chromosome V that are linked
      to both traits. This research represents the first molecular genetic research of
      IHN in potato.

PMID- 20803135
TI  - Secondary adaptation of memory-guided saccades.
AB  - Adaptation of saccade gains in response to errors keeps vision and action co
      registered in the absence of awareness or effort. Timing is key, as the visual
      error must be available shortly after the saccade is generated or adaptation does
      not occur. Here, we tested the hypothesis that when feedback is delayed, learning
      still occurs, but does so through small secondary corrective saccades. Using a
      memory-guided saccade task, we gave feedback about the accuracy of saccades that
      was falsely displaced by a consistent amount, but only after long delays. Despite
      the delayed feedback, over time subjects improved in accuracy toward the false
      feedback. They did so not by adjusting their primary saccades, but via directed
      corrective saccades made before feedback was given. We propose that saccade
      learning may be driven by different types of feedback teaching signals. One
      teaching signal relies upon a tight temporal relation with the saccade and
      contributes to obligatory learning independent of awareness. When this signal is
      ineffective due to delayed error feedback, a second compensatory teaching signal
      enables flexible adjustments to the spatial goal of saccades and helps maintain
      sensorimotor accuracy.

PMID- 20803136
TI  - Construction of stress-induced metabolic pathway from glucose to 1,3-propanediol
      in Escherichia coli.
AB  - 1,3-Propanediol is an important chemical widely used in polymer production, but
      its availability is being restricted owing to its expensive synthesis. The aim of
      this study was to engineer an Escherichia coli strain that can produce 1,3
      propanediol directly from glucose. We successfully constructed a stress-induced
      metabolic pathway from glucose to 1,3-propanediol in recombinant E. coli by the
      expression of gpd1 and gpp2 genes from Saccharomyces cerevisiae and dha operon
      from Klebsiella pneumoniae, respectively. Batch cultivation of the recombinant E.
      coli showed that 12.1 g/L 1,3-propanediol was accumulated in the culture without
      using any inducer.

PMID- 20803137
TI  - Proteome analysis of Azotobacter vinelandii ?arrF mutant that overproduces poly
      beta-hydroxybutyrate polymer.
AB  - Azotobacter vinelandii ArrF is an iron-responsive small RNA that is under
      negative control of Ferric uptake regulator protein. A. vinelandii ?arrF mutant
      that had a deletion of the entire arrF gene was known to overproduce poly-beta
      hydroxybutyrate (PHB). Proteins differentially expressed in the mutant were
      identified by gel-based proteomics and confirmed by real-time RT-PCR. 6
      Phosphogluconolactonase and E(1) component of pyruvate dehydrogenase complex,
      which leads to the production of NADPH and acetyl-CoA, were upregulated, while
      proteins in the tricarboxylic acid cycle that consumes acetyl-CoA were
      downregulated. Heat-shock proteins such as HSP20 and GroEL were highly
      overexpressed in the mutant. Antioxidant proteins such as Fe-containing
      superoxide dismutase (FeSOD), a putative oxidoreductase, alkyl hydroperoxide
      reductase, flavorprotein WrbA, and cysteine synthase were also overexpressed in
      the ?arrF mutant, indicating that the PHB accumulation is stressful to the cells.
      Upregulated in the ?arrF mutant were acetyl-CoA carboxylase, flagellin, and
      adenylate kinase, though the reasons for their overexpression are unclear. Among
      genes upregulated in the mutant, sodB coding for FeSOD and phbF encoding PHB
      synthesis regulator PhbF were negatively regulated by small RNA ArrF probably in
      an antisense mechanism. The deletion of arrF gene, therefore, would increase PhbF
      and FeSOD levels, which favors PHB synthesis in the mutant. On the other hand,
      glutamate synthetase, elongation factor-Tu, iron ABC transporter, and major outer
      membrane porin OprF were downregulated in the ?arrF mutant. Based on the results,
      it is concluded that multiple factors including the direct effect of small RNA
      ArrF might be responsible for the PHB overproduction in the mutant.

PMID- 20803138
TI  - Gene copy number and polyploidy on products formation in yeast.
AB  - Yeast, such as Saccharomyces cerevisiae or Kluyveromyces lactis is appropriate
      strain for ethanol production or some useful compounds production. Cellulases
      expressing yeast can ferment ethanol from cellulosic materials; however, the
      productivity should be increase more and more. To improve and engineer the
      productivity, the target gene(s) were introduced into yeast genome. Generally,
      using genetic engineering, increasing integrated gene numbers are increased, the
      expressed protein ability such as enzymatic activities are also increased. In
      this mini-review, we focused on the effect of integrated gene copy number and the
      polyploidy on the productivity such as enzymatic activity and/or product yield.

PMID- 20803139
TI  - Cloning and characterization of a thermostable and halo-tolerant endoglucanase
      from Thermoanaerobacter tengcongensis MB4.
AB  - A beta-1,4-endoglucanase (Cel5A) was cloned from the genomic DNA of saccharolytic
      thermophilic eubacterium Thermoanaerobacter tengcongensis MB4 and functionally
      expressed in Escherichia coli. Substrate specificity analysis revealed that Cel5A
      cleaves specifically the beta-1,4-glycosidic linkage in cellulose with high
      activity (294 U mg(-1); carboxymethyl cellulose sodium (CMC)). On CMC, kinetics
      of Cel5A was determined (K (m) 1.39 +/- 0.12 g l(-1); k (cat)/K (m) 1.41 +/- 0.13
      g(-1) s(-1)). Cel5A displays an activity optimum between 75 and 80  degrees C.
      Residues Glu187 and Glu289 were identified as key catalytic amino acids by
      sequence alignment. Interestingly, derived from a non-halophilic bacterium, Cel5A
      exhibits high residual activities in molar concentration of NaCl (3 M, 49.3%) and
      KCl (4 M, 48.6%). In 1 M NaCl, 82% of Cel5A activity is retained after 24 h
      incubation. Molecular Dynamics studies performed at 0 and 3 M NaCl, correlate the
      Cel5A stability to the formation of R-COO(-)...Na(+) ...(-)OOC-R salt bridges
      within the Cel5A tertiary structure, while activity possibly relates to the
      number of Na(+) ions trapped into the negatively charged active site, involving a
      competition mechanism between substrate and Na(+). Additionally, Cel5A is
      remarkably resistant in ionic liquids 1-butyl-3-methyllimidazolium chloride (1 M,
      54.4%) and 1-allyl-3-methylimidazolium chloride (1 M, 65.1%) which are promising
      solvents for cellulose degradation and making Cel5A an attractive candidate for
      industrial applications.

PMID- 20803140
TI  - Response of microbial community structure to microbial plugging in a mesothermic
      petroleum reservoir in China.
AB  - Microbial plugging, a microbial enhancement of oil recovery (MEOR) technique, has
      been applied in a candidate oil reservoir of Daqing Oil Field (China). The goal
      of this study is to monitor the survival of injected bacteria and reveal the
      response of microbial communities in field trial of microbial plugging through
      injection of selected microbial culture broth and nutrients. Culture-dependent
      enrichment and culture-independent 16S rDNA clone library methods were used. The
      results show that it was easy to activate targeted biopolymer-producing bacteria
      in a laboratory environment, and it was difficult for injected exogenous bacteria
      to survive. In addition, microbial communities in the oil reservoir also changed
      before and after the field trial. However, microbial communities, activated by
      fermentative medium for biopolymer-producing bacteria, appeared to show greater
      differences in the laboratory than in the natural reservoir. It was concluded
      that microbial populations monitoring was important to MEOR; results of response
      of microbial communities could provide a guide for the future field trials.

PMID- 20803141
TI  - Escherichia coli as a bioreporter in ecotoxicology.
AB  - Ecotoxicological assessment relies to a large extent on the information gathered
      with surrogate species and the extrapolation of test results across species and
      different levels of biological organisation. Bacteria have long been used as a
      bioreporter for genotoxic testing and general toxicity. Today, it is clear that
      bacteria have the potential for screening of other toxicological endpoints.
      Escherichia coli has been studied for years; in-depth knowledge of its
      biochemistry and genetics makes it the most proficient prokaryote for the
      development of new toxicological assays. Several assays have been designed with
      E. coli as a bioreporter, and the recent trend to develop novel, better advanced
      reporters makes bioreporter development one of the most dynamic in ecotoxicology.
      Based on in-depth knowledge of E. coli, new assays are being developed or
      existing ones redesigned, thanks to the availability of new reporter genes and
      new or improved substrates. The technological evolution towards easier and more
      sensitive detection of different gene products is another important aspect.
      Often, this requires the redesign of the bacterium to make it compatible with the
      novel measuring tests. Recent advances in surface chemistry and nanoelectronics
      open the perspective for advanced reporter based on novel measuring platforms and
      with an online potential. In this article, we will discuss the use of E. coli
      based bioreporters in ecotoxicological applications as well as some innovative
      sensors awaited for the future.

PMID- 20803142
TI  - Severe congenital neutropenia in a multigenerational family with a novel
      neutrophil elastase (ELANE) mutation.
AB  - We have analysed a family with nine congenital neutropenia patients in four
      generations, several of which we have studied in a long-term follow-up of over 25
      years. The patients were mild to severe neutropenic and suffered from various
      recurrent bacterial infections. Mutations in the genes ELANE, CSF3R and GFI1 have
      been reported in patients with autosomal dominant congenital neutropenias. Using
      a small-scale linkage analysis with markers around the ELANE, CSF3R, CSF3 and
      GFI1 genes, we were able to determine that the disease segregated with markers
      around the ELANE gene. We identified a novel mutation in the ELANE gene in all of
      the affected family members that was not present in any of the healthy family
      members. The mutation leads to an A28S missense mutation in the mature protein.
      None of these patients developed leukaemia. This is the first truly
      multigenerational family with mutations in ELANE as unambiguous cause of severe
      congenital neutropenia SCN.

PMID- 20803143
TI  - Synchronous occurrence of acute promyelocytic leukemia and non-Hodgkin lymphoma.

PMID- 20803144
TI  - Overexpression and characterization of an extracellular leucine aminopeptidase
      from Aspergillus oryzae.
AB  - Leucine aminopeptidase (LAP), an enzyme used in the food industry, is an
      exopeptidase that removes an amino acid residue, primarily leucine (Leu), from
      the N-terminus of peptides and protein substrates. In this study, we focused on
      the leucine aminopeptidase A (lapA) gene from Aspergillus oryzae RIB40. To purify
      and characterize the LapA, lapA was overexpressed in A. oryzae RIB40 using the
      amyB promoter. LAP activity in the culture supernatant of one transformant
      harboring the lapA expression plasmid was 33 times that of the host strain. LapA
      was purified from the culture supernatant of this lapA-overexpressing strain by
      column chromatography. The purified recombinant LapA had a molecular mass of 33
      kDa, and its N-terminal amino acid was the tyrosine at position 80 of the deduced
      amino acid sequence. Optimal enzyme activity was observed at 60 degrees C and pH
      8.5, and the enzyme was stable at temperatures up to 60 degrees C and in the pH
      range 7.5-11. In transcriptional analysis, lapA was induced under alkaline
      conditions and expressed at a relatively low level under normal conditions. LapA
      showed maximum hydrolyzing activity for the substrate leucine para-nitroanilide
      (Leu-pNA), followed by substrates Phe-pNA (39% activity compared with Leu-pNA),
      Met-pNA, Lys-pNA, and Arg-pNA. In addition, LapA preferentially hydrolyzed
      peptides longer than tripeptides.

PMID- 20803145
TI  - Bone marrow stem cells in clinical application: harnessing paracrine roles and
      niche mechanisms.
AB  - The being of any individual throughout life is a dynamic process relying on the
      capacity to retain processes of self-renewal and differentiation, both of which
      are hallmarks of stem cells. Although limited in the adult human organism,
      regeneration and repair do take place in virtue of the presence of adult stem
      cells. In the bone marrow, two major populations of stem cells govern the dynamic
      equilibrium of both hemopoiesis and skeletal homeostasis; the hematopoietic and
      the mesenchymal stem cells. Recent cell based clinical trials utilizing bone
      marrow-derived stem cells as therapeutic agents have revealed promising results,
      while others have failed to display as such. It is therefore imperative to strive
      to understand the mechanisms by which these cells function in vivo, how their
      properties can be maintained ex-vivo, and to explore further their recently
      highlighted immunomodulatory and trophic effects.

PMID- 20803146
TI  - Clinical application of stem cells in the cardiovascular system.
AB  - Regenerative medicine encompasses "tissue engineering" - the in vitro fabrication
      of tissues and/or organs using scaffold material and viable cells - and "cell
      therapy" - the transplantation or manipulation of cells in diseased tissue in
      vivo. In the cardiovascular system, tissue engineering strategies are being
      pursued for the development of viable replacement blood vessels, heart valves,
      patch material, cardiac pacemakers and contractile myocardium. Anecdotal clinical
      applications of such vessels, valves and patches have been described, but
      information on systematic studies of the performance of such implants is not
      available, yet. Cell therapy for cardiovascular regeneration, however, has been
      performed in large series of patients, and numerous clinical studies have
      produced sometimes conflicting results. The purpose of this chapter is to
      summarize the clinical experience with cell therapy for diseases of the
      cardiovascular system, and to analyse possible factors that may influence its
      outcome.

PMID- 20803147
TI  - Basilar artery dolichoectasia in childhood: evidence of vascular compromise.
AB  - INTRODUCTION: Dolichoectasia describes the elongation, dilatation and tortuosity
      of an arterial vessel. In adults, clinical presentation of basilar dolichoectasia
      (BD) is most often with ischaemic stroke. True BD has been very rarely reported
      in childhood, but the implication is of a congenital susceptibility. CASE REPORT:
      We describe two cases of infants with BD complicated by brainstem ischaemia.
      DISCUSSION: This first description of childhood BD associated with ischaemic
      infarction adds to the understanding of this rarely reported arteriopathy.

PMID- 20803148
TI  - Pancreatic trauma in children.
AB  - PURPOSE: To document the demographics, mechanisms and outcome of traumatic
      pancreatitis in children at a single large tertiary referral centre in Australia.
      METHODS: We undertook a 10-year retrospective audit of children admitted to the
      Royal Children's Hospital, Melbourne, Australia with a hospital coded diagnosis
      which included pancreatic injury between 1993 and 2002. Data included patient
      demographics, source of admission, mechanism of injury, pancreatic complications,
      associated injuries, intensive care unit admission, results of any operative
      findings, results of any acute computed tomography and/or ultrasound imaging of
      pancreas, selected laboratory findings and length of stay. RESULTS: We identified
      two distinct groups of patients in the 91 documented cases of pancreatic trauma
      (median age 8.0 years, range 0.6-15.8 years; M:F 2.5:1.0): 59 had a history of
      abdominal trauma and elevated serum lipase but no CT or ultrasound evidence of
      pancreatic injury (Group A); 32 had a history of abdominal trauma, elevated serum
      lipase but also had CT scan and/or ultrasound evidence of pancreatic injury
      (Group B). Patients with "less severe" injury based on normal imaging had a lower
      initial lipase level [Group A, median 651 U/L (interquartile range 520-1,324) vs.
      Group B, 1,608 U/L (interquartile range 680-3,526); p = 0.005] and shorter
      admission time [Group A, 9.0 days (interquartile range 5.5-15.5) vs. Group B,
      13.4 days (interquartile range 6.8-23.8); p = 0.04]. There were no differences
      with respect to mortality (Group A, 13.5% vs. Group B, 12.5%), but patients with
      evidence of injury on imaging were more likely to have surgical intervention (p =
      0.0001). The single most important overall cause of pancreatic trauma was
      involvement in a motor vehicle accident as a passenger or pedestrian. However, in
      children with high-grade ductal injury, bicycle handlebar injuries were most
      common. Associated injuries were common in both groups. CONCLUSION: Significant
      pancreatic injury can occur in the absence of abnormality on medical imaging.
      Pancreatic trauma commonly occurs in the context of multiple injuries after motor
      vehicle accidents in children and bicycle handlebar injuries, especially in boys.
      Most children can be treated conservatively, with surgical intervention being
      limited to high-grade ductal injury.

PMID- 20803149
TI  - Apoptotic protein expression, glycogen content, DNA ploidy and cell proliferation
      in hepatoblastoma subtyping and their role in prognostication.
AB  - PURPOSE: To evaluate Bcl-xL, Bax, PCNA, cytokeratin 19 (CK-19), glycogen content
      and DNA ploidy expression in hepatoblastoma (HB) and their prognostic value.
      METHODS: This retrospective study on 26 cases of HB involved DNA ploidy
      estimations separately for various subtypes on histological sections using image
      cytometry of Feulgen-stained smears. Glycogen content, PCNA, CK-19, Bax and Bcl
      xL expression on tissue sections were evaluated. THE outcome on follow-up (mean
      86 months) and Kaplan-Meier survival analysis were performed. RESULTS: Fetal
      areas were diploid (84%); embryonal areas were aneuploid (89.47%) (p < 0.001).
      PCNA labeling index was low in fetal (10.82%) and high in embryonal areas
      (59.85%) (p = 0.03). CK-19 was negative in fetal, but focally positive in
      embryonal areas. Bax was negative in fetal (80%) and positive in embryonal areas
      (88.23%) (p < 0.001); Bcl-xL was more frequently positive in fetal (90%) than
      embryonal areas (52.94%) (p = 0.02). Fetal cells were rich in glycogen. Kaplan
      Meier survival analysis showed good initial radiological response to chemotherapy
      (p = 0.009), glycogen content (p = 0.0137) and DNA diploid cases (p = 0.0429)
      were associated with good outcome on univariate analysis. Histology typing (p =
      0.085), Bcl-xL (p = 0.689), Bax (p = 0.27), CK-19 (p = 0.281), PCNA (p = 0.689),
      age (p = 0.24), sex (p = 0.5661), stage (p = 0.24) and alpha-fetoprotein levels
      (p = 0.49) were unrelated to outcome. Multivariate analysis showed glycogen
      content to be the most statistically significant variable (0.024). CONCLUSION:
      Fetal and embryonal areas show different staining patterns for PCNA, Bax and Bcl
      xL. DNA ploidy and glycogen content are significant prognostic variables.

PMID- 20803150
TI  - The usefulness of sebum check film for measuring the secretion of sebum.
AB  - Patients with atopic dermatitis (AD) often present with dry skin, and the reduced
      secretion of sebum may be responsible for the impaired skin barrier function. A
      sebum check film enables the patient to self-evaluate the skin sebum content.
      This study compared the sebum check film with a sebumeter. The skin sebum content
      of the forehead was measured using a sebum check film and a sebumeter. The
      findings of the sebum content of healthy controls showed that the sebum dot
      fields on the sebum check film were significantly correlated with the sebum
      content measured using the sebumeter (r = 0.774, p < 0.001). In addition, the
      sebum fields on the sebum check film of AD patients (n = 26) were significantly
      less than those on the sebum check film of the controls (n = 30; p < 0.05).
      Furthermore, the analysis of the sebum fields on the sebum check film of the AD
      patients was significantly correlated with their sebum content findings that were
      obtained using a sebumeter (r = 0.592, p < 0.01). These findings indicate that
      the sebum check film is easy to use for measuring the sebum secretion and is
      suitable for self-checking the sebum contents by AD patients for daily skin care.

PMID- 20803151
TI  - Surgery and postoperative radiotherapy a valid treatment for advanced
      oropharyngeal carcinoma.
AB  - Since 1992 we have prospectively included all head and neck cancer patients in
      our health region in a departmental based register. Our hospital takes care of
      all head and neck cancer patients in our health region consisting of
      approximately 1 million people. In 1997, we evaluated the results of the
      treatment of oropharyngeal cancer in the 1992-1997 period. On the basis of this
      evaluation, we changed our treatment policy for tonsillar and base of tongue
      carcinoma. We first changed the treatment for the lesions with worst prognosis,
      i.e., those with T3-T4 carcinomas, from radiotherapy only, to radical surgery and
      postoperative radiotherapy. We have since that time increasingly also operated
      the smaller oropharyngeal carcinomas. The 2 years' overall survival and disease
      specific survival for all patients diagnosed in the 1992-1997 period was 56 and
      63%, respectively. The results from a similar group of patients in the 6 years'
      period from 2000 to 2005, after the change in treatment, have increased to 83 and
      88%. When we looked at the subgroup of patients in the 2000-2005 period treated
      with surgery and postoperative radiotherapy, 45 out of 69 patients (65%)
      presenting with an oropharyngeal cancer were fit for operation. With radical
      surgery and postoperative radiation therapy, the 2 years overall survival is now
      91%. The 2-year disease-specific survival is 96% and the locoregional control is
      98%. This is a marked improvement as compared to radiotherapy alone and
      definitely competitive with modern radiochemotherapy.

PMID- 20803152
TI  - Responses of muscle mass, strength and gene transcripts to long-term heat stress
      in healthy human subjects.
AB  - The present study was performed to investigate the effects of long-term heat
      stress on mass, strength and gene expression profile of human skeletal muscles
      without exercise training. Eight healthy men were subjected to 10-week
      application of heat stress, which was performed for the quadriceps muscles for 8
      h/day and 4 days/week by using a heat- and steam-generating sheet. Maximum
      isometric force during knee extension of the heated leg significantly increased
      after heat stress (~5.8%, P < 0.05). Mean cross-sectional areas (CSAs) of vastus
      lateralis (VL, ~2.7%) and rectus femoris (~6.1%) muscles, as well as fiber CSA
      (8.3%) in VL, in the heated leg were also significantly increased (P < 0.05).
      Statistical analysis of microarrays (SAM) revealed that 10 weeks of heat stress
      increased the transcript level of 925 genes and decreased that of 1,300 genes,
      and gene function clustering analysis (Database for Annotation, Visualization and
      Integrated Discovery: DAVID) showed that these regulated transcripts stemmed from
      diverse functional categories. Transcript level of ubiquinol-cytochrome c
      reductase binding protein (UQCRB) was significantly increased by 10 weeks of heat
      stress (~3.0 folds). UQCRB is classified as one of the oxidative phosphorylation
      associated genes, suggesting that heat stress can stimulate ATP synthesis. These
      results suggested that long-term application of heat stress could be effective in
      increasing the muscle strength associated with hypertrophy without exercise
      training.

PMID- 20803153
TI  - The effects of a respiratory warm-up on the physical capacity and ventilatory
      response in paraplegic individuals.
AB  - A respiratory warm-up (RWU) can improve exercise performance in able-bodied
      athletes. However, its effects in paraplegic individuals are unknown. On two
      occasions, nine male active paraplegic individuals performed an arm cranking test
      to exhaustion at 85% of their peak power output. In the intervention (INT) trial,
      this procedure was preceded by a RWU, whereas in the control (CON) trial, no RWU
      was conducted. Time to exhaustion was reduced following the RWU (CON vs. INT: 497
      +/- 163 vs. 425 +/- 126 s, P = 0.02). Pulmonary ventilation was increased in the
      middle (74.8 +/- 18.0 vs. 78.3 +/- 19.6 L min(-1), P = 0.01) and end (86.1 +/-
      20.4 vs. 95.4 +/- 23.3 L min(-1), P = 0.01) phase of exercise following the RWU.
      Forced expiratory volume in 1 s (FEV1) was reduced following the RWU (3.44 +/-
      0.45 vs. 3.27 +/- 0.54 L, P = 0.02). The decrease in FEV1 following the RWU and
      the higher pulmonary ventilation during the INT trial suggest that the RWU
      fatigued the respiratory system, and hence reduced performance capacity. It is
      possible that the RWU used in this study is not suitable for paraplegic
      individuals, as their respiratory system is limited due to their disability. We
      conclude that a RWU impaired exercise performance in a group of active paraplegic
      individuals as a result of respiratory muscle fatigue.

PMID- 20803154
TI  - Hormonal response to Taekwondo fighting simulation in elite adolescent athletes.
AB  - Exercise training efficiency depends on the training load, as well as on the
      athlete's ability to tolerate it. The aim of the present study was to evaluate
      the effect of fighting simulation (3 fights, 6 min each, 30 min rest between
      fights) on anabolic (IGF-I, LH, FSH, estradiol, and testosterone) and catabolic
      hormones (cortisol) in elite, male (n = 10) and female (n = 10) adolescent (12-17
      years) Taekwondo fighters. Blood samples were collected before the first and
      immediately after the third fight. The fighting simulation practice led to
      significant (p < 0.05) decreases in IGF-I (males -27.1 +/- 25.6, females -22.4 +/
      36.3 ng/ml), LH (males -0.7 +/- 1.2, females -2.3 +/- 3.3 U/L), and FSH (males 
      0.9 +/- 0.5, females -1.5 +/- 1.1 U/L), and to a significant increase (p < 0.05)
      in cortisol (males 141.9 +/- 30.1, females 64.1 +/- 30.6 mcg/dL) in both genders.
      Fighting simulation decreases in testosterone (males -1.9 +/- 1.6, females -0.02
      +/- 0.06 ng/mL), and free androgen index (males -20.1 +/- 21.5, females -0.3 +/-
      0.5) were significant (p < 0.05) only in male fighters. Exercise had no
      significant effect on estradiol, sex-hormone-binding globulins or thyroid
      function tests. Our data demonstrate that the physiologic and psychologic strain
      of a Taekwondo fighting simulation day led to a catabolic-type circulating
      hormonal response.

PMID- 20803155
TI  - Rotenoids from Lablab purpureus L. and their bioefficacy against human disease
      vectors.
AB  - Various plant parts of Lablab purpureu s L. were collected and analyzed
      separately for their rotenoid content. Among the plant parts, the maximum content
      was in the roots and minimum in the seeds. The identity of different rotenoids
      was confirmed by melting point, mixed melting point, UV, and infrared spectral
      studies and gas-liquid chromatography. Six rotenoids (deguelin, dehydrodeguelin,
      rotenol, rotenone, tephrosin, and sumatrol) were isolated, identified, and
      quantified both in vivo and in vitro. Toxicological studies of extracts showed
      bioefficacy against causal agents of malaria, dracunculiasis, and amoebiasis.

PMID- 20803156
TI  - Variable renal phenotype in a family with an INF2 mutation.
AB  - Recent advances in the genetics of glomerular diseases have identified several
      causative genes of nephrotic syndrome and/or glomerular proteinuria. In 2010, the
      INF2 gene, which encodes a member of the formin family of actin-regulating
      proteins, was identified as a novel causative gene of the autosomal dominant form
      of focal segmental glomerulosclerosis (FSGS). Here, we describe an additional
      familial case of FSGS associated with INF2 mutations. In the family, two siblings
      and their father had a heterozygous p.E220K mutation on INF2. This mutation
      manifested in these three individuals as incidentally detected proteinuria
      without overt nephrotic syndrome, but at different ages of 7, 9, and 30 years,
      respectively. Two siblings had nephrotic range proteinuria, and one developed end
      stage renal disease 5 years later. Conversely, their father had a modest degree
      of proteinuria, and maintained normal renal function until age 47. A renal biopsy
      of one of the siblings revealed FSGS with irregular podocyte foot process
      morphology and focal glomerular basement membrane changes. This is the second
      paper describing a familial case of FSGS associated with INF2 mutations as well
      as intrafamilial phenotype variability.

PMID- 20803157
TI  - L5-S1 disc replacement after two previous fusion surgeries for scoliosis.
AB  - Following scoliosis surgery, lumbar motion segment degeneration below the level
      of fusion is not uncommon. Especially long fusions extending to the mid and lower
      lumbar spine increase the likelihood of degeneration of the remaining motion
      segments. The management for these patients is controversial and depends on the
      clinical presentation and level of degeneration. The increasing confidence in
      motion-preserving technology leads to a dilemma on whether to fuse the remaining
      lumbar levels or risk utilising disc arthroplasty to preserve the remaining
      motion segments and facilitate coronal balance in patients with previous long
      fusion for scoliosis. We present an interesting case of a 44-year-old lady, who
      underwent two-stage corrective surgery for progressive idiopathic scoliosis at
      the age of 22 years. In the first stage, she had T11-L3 anterior fusion, whilst
      in the second stage posterior fusion was done from T5 to L3. At 22 years after
      the initial surgery, she presented with worsening low back pain and bilateral L4
      radicular symptoms. MRI scan confirmed severe disc degeneration at L3-4 and L5-S1
      levels with preserved L4-5 disc. She initially underwent L3-L4 decompression and
      posterolateral fusion at that level, which relieved her radicular symptoms.
      However, she had persistent pain at the lumbosacral junction with Modic I
      changes. The options of an anterior L5-S1 fusion or disc replacement were
      considered and discussed with the patient. The disc replacement option was
      decided upon with the patient, as anterior fusion was judged to increase the risk
      of coronal imbalance. At the 1-year follow-up, she reported significant
      improvement in the back pain. The radiographs at 1 year showed satisfactory
      position and function of the artificial disc replacement. The disc was flexed
      laterally, accommodating the coronal balance of the spine. We conclude that L5-S1
      motion segment can be preserved with artificial disc replacement in patients with
      previous long fusion for scoliosis surgery. The real difficulty arises when
      choosing between disc replacement and extension of fusion. In our patient, the
      disc replacement has worked well so far. However, the disc is clearly at a
      mechanical disadvantage, and loss of function in the mid- or long term would not
      be surprising.

PMID- 20803159
TI  - Time- and temperature-dependent autolysis of urinary bladder epithelium during ex
      vivo preservation.
AB  - Morphological and functional preservation of urinary bladder epithelium
      urothelium after extirpation from an organism enables physiological studies of
      that tissue and provides the basis for successful organ transplantations. The aim
      of this study was to determine the optimal temperature for maintaining urothelium
      in ex vivo conditions. Mouse urinary bladders were kept at the three temperatures
      usually used for maintaining tissue during transportation: at the temperature of
      melting ice (1 degrees C), at room temperature (22-24 degrees C), and at the body
      temperature of most mammals (37 degrees C). Autolytic structural changes were
      followed with electron microscopy, while destruction of cytoskeleton and
      intercellular junctions was observed by immunolabeling. The first ultrastructural
      changes, swelling of mitochondria and necrosis of individual cells, became
      evident 30 min after extirpation if the tissue was kept at 1 degrees C. After 60
      and 120 min in ex vivo conditions, the most severe changes with increasing plasma
      membrane ruptures were detected at 1 degrees C, while at room temperature only
      mild changes were detected. At 37 degrees C, the extent of ultrastructural
      changes was between those of the other two experimental temperatures. Autolytic
      destruction of cytoskeleton and intercellular junctions was not observed before 2
      h after extirpation. After 4 h, severe degradation of cytokeratin 20 and
      microtubules were found at 1 degrees C and 37 degrees C, while being almost
      undisturbed at room temperature. On the other hand, the reduction of desmoplakin
      and ZO-1 labeling was more evident at 37 degrees C than at 1 degrees C and room
      temperature. These findings provide evidence that room temperature is most
      appropriate for short ex vivo preservation of urothelial tissue.

PMID- 20803158
TI  - Development and application of probes for labeling the actin cytoskeleton in
      living plant cells.
AB  - The actin cytoskeleton is one of the most important components of eukaryotic
      cytoskeletons. It participates in numerous crucial procedures of cells and has
      been studied by using various methods. The development and application of
      appropriate probes for actin visualization is the first and foremost step for
      functional analysis of actin in vivo. Since the actin cytoskeleton is a highly
      dynamic and sensitive structure, methods previously used to visualize actin often
      harm cells and cannot reveal the native state of the actin cytoskeleton in living
      cells. The development of labeling technologies for living plant cells,
      especially the emergence and application of green fluorescent protein-tagged
      actin markers, has provided new insights into the structure and function of the
      actin cytoskeleton in vivo. There has been a number of probes for actin labeling
      in living plant cells though they each present different advantages and defects.
      In this review, we discuss and compare those widely used methods for actin
      visualization and analysis.

PMID- 20803160
TI  - Scanning electron microscopy (SEM) and X-ray dispersive spectrometry evaluation
      of direct laser metal sintering surface and human bone interface: a case series.
AB  - Recent studies have shown that direct laser metal sintering (DLMS) produces
      structures with complex geometry and consequently that allow better
      osteoconductive properties. The aim of this patient report was to evaluate the
      early bone response to DLMS implant surface retrieved from human jaws. Four
      experimental DLMS implants were inserted in the posterior mandible of four
      patients during conventional dental implant surgery. After 8 weeks, the micro
      implants and the surrounding tissue were removed and prepared for scanning
      electron microscopy (SEM) and histomorphometric analysis to evaluate the bone
      implant interface. The SEM and EDX evaluations showed a newly formed tissue
      composed of calcium and phosphorus. The bone-to-implant contact presented a mean
      of 60.5 +/- 11.6%. Within the limits of this patient report, data suggest that
      the DLMS surfaces presented a close contact with the human bone after a healing
      period of 8 weeks.

PMID- 20803161
TI  - Histological evaluation of vertical laser channels from ablative fractional
      resurfacing: an ex vivo pig skin model.
AB  - Ablative fractional resurfacing (AFR) represents a new treatment potential for
      various skin conditions and new laser devices are being introduced. It is
      important to gain information about the impact of laser settings on the
      dimensions of the created laser channels for obtaining a safe and efficient
      treatment outcome. The aim of this study was to establish a standard model to
      document the histological tissue damage profiles after AFR and to test a new
      laser device at diverse settings. Ex vivo abdominal pig skin was treated with a
      MedArt 620, prototype fractional carbon dioxide (CO(2)) laser (Medart, Hvidovre,
      Denmark) delivering single microbeams (MB) with a spot size of 165 MUm. By using
      a constant pulse duration of 2 ms, intensities of 1-18 W, single and 2-4 stacked
      pulses, energies were delivered in a range from 2-144 mJ/MB. Histological
      evaluations included 3-4 high-quality histological measurements for each laser
      setting (n = 28). AFR created cone-shaped laser channels. Ablation depths varied
      from reaching the superficial dermis (2 mJ, median 41 MUm) to approaching the
      subcutaneous fat (144 mJ, median 1,943 MUm) and correlated to the applied energy
      levels in an approximate linear relation (r(2) = 0.84, p < 0.001). The dermal
      ablation width increased slightly within the energy range of 4-144 mJ (median 163
      MUm). The thickness of the coagulation zone reached a plateau around 65 MUm at
      energies levels above 16 mJ. The calculated volumes of ablated tissue increased
      with increasing energies. We suggest this ex vivo pig skin model to characterize
      AFR laser channels histologically.

PMID- 20803162
TI  - Molecular dynamics simulations of cytochrome c unfolding in AOT reverse micelles:
      The first steps.
AB  - This paper explores the reduced form of horse cytochrome c confined in reverse
      micelles (RM) of sodium bis-(2-ethylhexyl) sulfosuccinate (AOT) in isooctane by
      molecular dynamics simulation. RMs of two sizes were constructed at a water
      content of W (o) = [ H2O ]/[AOT] = 5.5 and 9.1. Our results show that the protein
      secondary structure and the heme conformation both depend on micellar hydration.
      At low hydration, the protein structure and the heme moiety remain stable,
      whereas at high water content the protein becomes unstable and starts to unfold.
      At W (o) = 9.1 , according to the X-ray structure, conformational changes are
      mainly localized on protein loops and around the heme moiety, where we observe a
      partial opening of the heme crevice. These findings suggest that within our time
      window (10ns), the structural changes observed at the heme level are the first
      steps of the protein denaturation process, previously described experimentally in
      micellar solutions. In addition, a specific binding of AOT molecules to a few
      lysine residues of the protein was found only in the small-sized RM.

PMID- 20803163
TI  - Multiple induced mutagenesis for improvement of ethanol production by
      Kluyveromyces marxianus.
AB  - Kluyveromyces marxianus GX-15 was mutated multiple times by alternately treatment
      with UV irradiation and NTG for two cycles. Four mutant strains with improved
      ethanol yield were obtained. The maximum ethanol concentration, ethanol yield
      coefficient and theoretical ethanol yield of the best mutant strain, GX-UN120,
      was 69 g/l, 0.46 g/g and 91%, respectively, when fermenting 150 g glucose/l at 40
      degrees C. The corresponding values for GX-15 were 58 g/l, 0.39 g/g and 76%,
      respectively. GX-UN120 grew well in 11% (v/v) of ethanol, while GX-15 could not
      grow when ethanol was greater than 8% (v/v).

PMID- 20803164
TI  - Isolation of a Pseudomonas aeruginosa strain from soil that can degrade
      polyurethane diol.
AB  - Polyurethane diol (PUR-diol), a synthetic polymer, is widely used as a modifier
      for water-soluble resins and emulsions in wood appliances and auto coatings. Non
      biodegradability of polyurethanes (PUR) and PUR-based materials poses a threat to
      environment that has led scientists to isolate microbes capable of degrading PUR.
      However, the bio-degradation of PUR-diol has not yet been reported. In this
      study, we report isolation of a soil bacterium that can survive using PUR-diol as
      sole carbon source. PUR-diol degradation by the organism was confirmed by thin
      layer chromatographic analysis of the conditioned medium obtained after the
      growth wherein a significant reduction of PUR-diol was observed compared to non
      inoculated medium. To quantify the PUR-diol degradation, a sensitive assay based
      on High Performance Thin Layer Chromatography has been developed that showed 32%
      degradation of PUR-diol by the organism in 10 days. Degradation kinetics showed
      the maximal depletion of PUR-diol during logarithmic growth of the organism
      indicating a direct relation between the growth and PUR-diol degradation.
      Mutagenic study and GC-MS analysis revealed that esterase activity is involved in
      this degradation event. The ribotyping and metabolic fingerprinting analysis
      showed that this organism is a strain of Pseudomonous aeruginosa (P. aeruginosa).
      It has also been observed that this strain is able to degrade Impranil DLNTM, a
      variety of commercially available PUR. Therefore this study identifies a new
      bacterium from soil that has the potential to reduce PUR-related waste burden and
      adds a new facet to diverse functional activities of P. aeruginosa.

PMID- 20803166
TI  - Nutrition assessment of horse-racing athletes.
AB  - Athletes involved in horse racing face weight restrictions like wrestlers and
      dancers; however, the literature is sparse pertaining to nutritional habits of
      jockeys. The practice of "making weight" causes these athletes to engage in
      potentially unhealthy practices. A gap in nutritionally sound practices and
      methods used by jockeys was identified and a desire for nutrition education was
      expressed to Cooperative Extension of Delaware by representatives of the riders
      at Delaware Park Race Track. Nutrition assessment was done using the Nutrition
      Care Process. Twenty jockeys were interviewed using an assessment form developed
      to target areas of disordered eating. Body mass index (BMI), mean weight loss on
      race day, methods of weight loss and ease of weight maintenance were examined.
      The jockeys were also asked for areas they wished to receive nutrition education
      on in the future. The BMI of the 20 jockeys ranged from 17.0 to 21.4 during
      racing season, with only one jockey in the "underweight" category. This range
      increased to 19.1-24.0 when the riders were not riding. The most common method of
      weight loss was the use of steam rooms, to lose an average 2.5 lb in 1 day. Eight
      of 20, the most common response, reported it very easy to maintain their racing
      weight. The jockeys reported interest in future education sessions on meal
      planning and healthy food ideas. The assessment was used as the basis to develop
      nutrition education materials and presentations for the riders at the race track.

PMID- 20803165
TI  - Bibliotherapy as a treatment for depression in primary care.
AB  - This study was designed to determine whether a physician-delivered bibliotherapy
      prescription would compare favorably with the prevailing usual care treatment for
      depression in primary care (that often involves medication) and potentially offer
      an alternative. Six family physicians were trained to write and deliver
      prescriptions for cognitive-behavioral bibliotherapy. Thirty-eight patients were
      randomly assigned to receive either usual care or a behavioral prescription to
      read the self-help book, Feeling Good (Burns, D. D. (1999). Feeling good: The new
      mood therapy. New York: HarperCollins). The treatment groups did not differ in
      terms of overall outcome variables. Patients in both treatment groups reported
      statistically significant decreases in depression symptoms, decreases in
      dysfunctional attitudes, and increases in quality of life. Although not
      statistically significant, the mean net medical expenses in the behavioral
      prescription group were substantially less. This study provided empirical
      evidence that a behavioral prescription for Feeling Good may be as effective as
      standard care, which commonly involves an antidepressant prescription.

PMID- 20803167
TI  - Cost-benefit analysis of childhood asthma management through school-based clinic
      programs.
AB  - Asthma is a leading chronic illness among American children. School-based health
      clinics (SBHCs) reduced expensive ER visits and hospitalizations through better
      healthcare access and monitoring in select case studies. The purpose of this
      study was to examine the cost-benefit of SBHC programs in managing childhood
      asthma nationwide for reduction in medical costs of ER, hospital and outpatient
      physician care and savings in opportunity social costs of lowing absenteeism and
      work loss and of future earnings due to premature deaths. Eight public data
      sources were used to compare costs of delivering primary and preventive care for
      childhood asthma in the US via SBHC programs, including direct medical and
      indirect opportunity costs for children and their parents. The costs of nurse
      staffing for a nationwide SBHC program were estimated at $4.55 billion compared
      to the estimated medical savings of $1.69 billion, including ER, hospital, and
      outpatient care. In contrast, estimated total savings for opportunity costs of
      work loss and premature death were $23.13 billion. Medical savings alone would
      not offset the expense of implementing a SBHC program for prevention and
      monitoring childhood asthma. However, even modest estimates of reducing
      opportunity costs of parents' work loss would be far greater than the expense of
      this program. Although SBHC programs would not be expected to affect the
      increasing prevalence of childhood asthma, these programs would be designed to
      reduce the severity of asthma condition with ongoing monitoring, disease
      prevention and patient compliance.

PMID- 20803168
TI  - Thought-action fusion in childhood: measurement, development, and association
      with anxiety, rituals and other compulsive-like behaviors.
AB  - A new inventory assessing thought-action fusion (TAF) in children is presented.
      We explore the psychometric properties of this instrument and examine the
      associations between TAF, ritualistic and compulsive-like behavior (CLB) and
      anxiety. Three hundred thirteen children ages 7-14 (M = 10.16, SD = 1.92)
      representing six grades (grouped into three grade levels (grades 2-3, 4-5, and 6
      7) completed the Thought-action Fusion Inventory for Children (TAFIC) and the
      Child Revised Manifest Anxiety Scale. One hundred thirty-five parents or
      guardians completed the Childhood Routines Inventory. Results revealed high
      internal consistency in the TAFIC (Cronbach's alpha = .92). TAF scores changed
      with age: Older children reported less TAF than younger children. Stepwise
      multiple regression analyses revealed that: (1) physiological anxiety predicted
      CLB in early childhood; (2) TAF predicted CLB in older children. Consistent with
      structural developmental theories, TAF changes throughout development, but plays
      a role in the normative regulation of affective states, as well as in the
      development of ritualistic compulsive like behavior in children.

PMID- 20803169
TI  - Carbonic anhydrase inhibition with natural products: novel chemotypes and
      inhibition mechanisms.
AB  - Five genetically distinct classes of carbonic anhydrases (CAs, EC 4.2.1.1) are
      present in organisms all over the phylogenetic tree (alpha-, beta-, gamma-, delta
      , and zeta-families). These metalloenzymes catalyze CO(2) hydration to
      bicarbonate and protons. Inhibition of alpha-CAs from vertebrates, including
      humans, with sulfonamides was exploited clinically for decades for various
      classes of diuretics and systemically acting antiglaucoma agents, whereas newer
      inhibitors are used as topically acting antiglaucoma drugs, anticonvulsants,
      antiobesity, antipain and antitumor agents/diagnostic tools. Recently, novel
      interesting chemotypes, in addition to the sulfonamide and sulfamate were
      discovered, many of which are based on natural products, such as
      phenols/polyphenols, phenolic acids, and coumarins. Their detailed mechanism of
      inhibition has been explained by means of kinetic and X-ray crystallographic
      studies, and can be used for the rational drug design of other agents. Possible
      applications for these new chemotypes in drug design of CA inhibitors are
      envisaged and discussed in detail in this review.

PMID- 20803170
TI  - Oral LD50 toxicity modeling and prediction of per- and polyfluorinated chemicals
      on rat and mouse.
AB  - Quantitative structure-activity relationship (QSAR) analyses were performed using
      the LD(50) oral toxicity data of per- and polyfluorinated chemicals (PFCs) on
      rodents: rat and mouse. PFCs are studied under the EU project CADASTER which uses
      the available experimental data for prediction and prioritization of toxic
      chemicals for risk assessment by using the in silico tools. The methodology
      presented here applies chemometrical analysis on the existing experimental data
      and predicts the toxicity of new compounds. QSAR analyses were performed on the
      available 58 mouse and 50 rat LD(50) oral data using multiple linear regression
      (MLR) based on theoretical molecular descriptors selected by genetic algorithm
      (GA). Training and prediction sets were prepared a priori from available
      experimental datasets in terms of structure and response. These sets were used to
      derive statistically robust and predictive (both internally and externally)
      models. The structural applicability domain (AD) of the models were verified on
      376 per- and polyfluorinated chemicals including those in REACH preregistration
      list. The rat and mouse endpoints were predicted by each model for the studied
      compounds, and finally 30 compounds, all perfluorinated, were prioritized as most
      important for experimental toxicity analysis under the project. In addition,
      cumulative study on compounds within the AD of all four models, including two
      earlier published models on LC(50) rodent analysis was studied and the cumulative
      toxicity trend was observed using principal component analysis (PCA). The
      similarities and the differences observed in terms of descriptors and
      chemical/mechanistic meaning encoded by descriptors to prioritize the most toxic
      compounds are highlighted.

PMID- 20803171
TI  - A novel approach to propagation pattern analysis in intracardiac atrial
      fibrillation signals.
AB  - The purpose of this study is to investigate propagation patterns in intracardiac
      signals recorded during atrial fibrillation (AF) using an approach based on
      partial directed coherence (PDC), which evaluates directional coupling between
      multiple signals in the frequency domain. The PDC is evaluated at the dominant
      frequency of AF signals and tested for significance using a surrogate data
      procedure specifically designed to assess causality. For significantly coupled
      sites, the approach allows also to estimate the delay in propagation. The methods
      potential is illustrated with two simulation scenarios based on a detailed ionic
      model of the human atrial myocyte as well as with real data recordings, selected
      to present typical propagation mechanisms and recording situations in atrial
      tachyarrhythmias. In both simulation scenarios the significant PDCs correctly
      reflect the direction of coupling and thus the propagation between all recording
      sites. In the real data recordings, clear propagation patterns are identified
      which agree with previous clinical observations. Thus, the results illustrate the
      ability of the novel approach to identify propagation patterns from intracardiac
      signals during AF, which can provide important information about the underlying
      AF mechanisms, potentially improving the planning and outcome of arrhythmia
      ablation.

PMID- 20803172
TI  - In vivo cellular MRI of dendritic cell migration using micrometer-sized iron
      oxide (MPIO) particles.
AB  - PURPOSE: This study seeks to assess the use of labeling with micron-sized iron
      oxide (MPIO) particles for the detection and quantification of the migration of
      dendritic cells (DCs) using cellular magnetic resonance imaging (MRI).
      PROCEDURES: DCs were labeled with red fluorescent MPIO particles for detection by
      cellular MRI and a green fluorescent membrane dye (PKH67) for histological
      detection. MPIO-labeled DCs or unlabeled control DCs were injected into mice
      footpads at two doses (0.1 * 10(6) and 1 * 10(6)). Images were acquired at 3
      Tesla before DC injection and 2, 3, and 7 days post-DC injection. RESULTS:
      Labeling DCs with MPIO particles did not affect viability, but it did alter
      markers of DC activation and maturation. MRI and fluorescence microscopy allowed
      for the detection of MPIO-labeled DCs within the draining popliteal nodes after
      their injection into the footpad. CONCLUSIONS: This paper presents the first
      report of the successful use of fluorescent MPIO particles to label and track DC
      migration.

PMID- 20803173
TI  - t10,c12-18:2-induced milk fat depression is less pronounced in cows fed high
      concentrate diets.
AB  - In intensively reared dairy cows, milk fat secretion is reduced in response to
      high-concentrate diets and it is often referred to as the "milk fat depression"
      (MFD) syndrome. Some trans fatty acid (FA) isomers produced in the rumen of the
      cows, including t10,c12-18:2, are known for their inhibitory effect on mammary
      lipogenesis. To study whether this effect depends on the basal diet, duodenal
      infusions of t10,c12-18:2 were performed on cows fed four different diets (a
      factorial arrangement of forage:concentrate ratio and linseed oil
      supplementation). The overall response obtained with t10,c12-18:2 infusion was
      consistent with previous studies: a decrease in milk fat content and yield
      without significant variations in milk yield. Mean transfer efficiency of infused
      t10,c12-18:2 was 19.6%. However, the decrease in milk fat and FA yields (both de
      novo synthesis and preformed long-chain FA) was less pronounced in cows fed high
      concentrate diets (-27% of the initial level), compared with cows fed low
      concentrate diets (-42% of initial level). This difference was independent of
      dietary oil supplementation and milk FA yield before infusion. Results pertaining
      to effects of dietary forage:concentrate ratio were confirmed by statistical meta
      analysis of data from previously published t10,c12-18:2 infusion experiments.
      This study shows that in cows fed MFD diets the mammary gland becomes more
      resistant to or experiences a lower response potential to further inhibition of
      lipogenesis and/or delta-9 desaturation of FA.

PMID- 20803174
TI  - The mechanism of Cordyceps sinensis and strontium in prevention of osteoporosis
      in rats.
AB  - The effects of Cordyceps sinensis (Caterpillar fungus) and strontium ranelate on
      ovariectomized osteopenic rats was studied in this paper. After the rats were
      treated orally with C. sinensis, strontium, and C. sinensis rich in strontium
      ranelate (CSS) respectively, serum alkaline phosphatase (ALP), tartarate
      resistant acid phosphatase (TRAP), serum osteocalcin (OC), homocysteine, C
      terminal crosslinked telopeptides of collagen type I (CTX), estradiol, and
      interferon-gamma (IFN-gamma) level were examined. The beneficial effects of CSS
      on improvement of osteoporosis in rats were attributable mainly to decrease ALP
      activity, TRAP activity, CTX level, and IFN-gamma level. At the same time, CSS
      also increase the OC and estradiol level in ovariectomized osteopenic rats. This
      study demonstrates the value of C. sinensis rich in strontium ranelate in the
      management of postmenopausal osteoporosis in humans.

PMID- 20803175
TI  - Expression and localization of the orexin-1 receptor (OX1R) after traumatic brain
      injury in mice.
AB  - Orexins are neuropeptides that have a wide range of physiological effects, and
      recent studies have suggested that the orexin system may be involved in traumatic
      brain injury. However, the expression and localization of orexin receptors have
      not been examined yet under brain injury conditions. In the present study, we
      used immunohistochemical techniques to investigate the expression of orexin-1
      receptor (OX1R) and its time-dependent changes in the mouse brain after
      controlled cortical impact (CCI) injury. OX1R-like immunoreactivity was first
      detected 6 h after injury in the surrounding penumbra of the injury. The
      intensity of this immunoreactivity was increased at 12 h, peaked at day 1, and
      then decreased from day 2 to day 7. To identify the cellular localization of
      OX1R, we also performed double-immunohistochemical staining with OX1R and several
      cell marker antibodies. OX1R-like immunopositive cells were clearly co-localized
      with immunoreactivity for the neuronal marker NeuN at day 7. It was also
      expressed on the periphery of cells immunopositive for CD11b, a microglial cell
      marker, at days 1 and 7. These results suggest that orexin and its receptor may
      play roles in traumatic brain injury, and that OX1R is induced in neurons and
      microglial cells after traumatic brain injury.

PMID- 20803176
TI  - A child with serious Chikungunya virus (CHIKV) infection requiring intensive
      care, after an outbreak.
AB  - A 5 1/2-yr-old boy presented with high grade fever for 4 days, and cervical
      adenitis, body ache, arthralgia, followed by sudden onset of breathlessness. He
      had clinical, electrocardiographic and echo evidence of myocarditis and
      congestive cardiac failure. An enzyme-linked immunosorbent assay (MAC-IgM ELISA)
      with serum collected 5 days after disease onset showed IgM antibodies to CHIKV.
      He was managed conservatively and started showing symptomatic improvement by 3
      days. At discharge, a repeat Echocardiogram (a week later) showed normal left
      ventricular (LV) function with mild Mitral regurgitation. On follow up, after 2
      months, child remains asymptomatic. Other common aetiological agents were
      screened for and found negative. This may indicate a probable cardiac tropism for
      the virus.

PMID- 20803177
TI  - H1N1 influenza in a preterm neonate.

PMID- 20803178
TI  - Pediatric vasculitides: a generalists approach.
AB  - Vasculitis is defined as the presence of inflammation in a blood vessel that may
      occur as a primary process or secondary to an underlying disease. Primary
      vasculitides are rare in children. These are defined by both the size of vessels
      involved and the type of inflammatory response. Clinical features consist of
      multi-organ involvement on a background of constitutional features reflecting the
      size and location of the blood vessels involved. Whilst some vasculitides are
      best diagnosed clinically, many forms require sophisticated imaging and other
      investigations (auto antibodies) to reveal the correct diagnosis. Prompt
      recognition and treatment is crucial as many of the vasculitides cause
      significant morbidity or mortality. Treatment options range from symptomatic
      therapy, immunosuppresive agents, intravenous immunoglobulin (IVIG) or biologic
      agents and are determined by the type of vasculitis, the severity of the
      inflammation, and the organ systems affected. Early detection and aggressive
      treatment is crucial for the best outcomes in the most severe forms of childhood
      vasculitis.

PMID- 20803179
TI  - Overactive bladder after sling surgery.
AB  - Midurethral sling surgery has become the new gold standard for the management of
      stress urinary incontinence. A significant number of patients will have
      preoperative symptoms of overactive bladder (OAB), including urgency, frequency,
      nocturia, and/or urgency urinary incontinence; however, 5% to 25% of women will
      report persistent, worsening, or de novo OAB after sling surgery. Some cases of
      OAB after sling surgery are known complications that should be recognized
      promptly and corrected, including urinary tract infection, urinary tract foreign
      body, and bladder outlet obstruction. For the remainder, the diagnosis and
      management of idiopathic postoperative OAB can be complicated. Preoperative
      clinical and urodynamic factors, as well as the choice of sling, may be helpful
      in predicting these patients and counseling them appropriately. When standard
      conservative therapy for OAB fails, sling incision, sacral neuromodulation, and
      botulinum toxin may be useful adjuncts.

PMID- 20803181
TI  - Small cell carcinoma of vulva: curative multimodal treatment in face of
      resistance to initial standard chemotherapy.
AB  - BACKGROUND AND PURPOSE: Extrapulmonary small cell carcinoma (EPSCC) is a rare
      disease, which has a slightly better prognosis than small cell lung cancer, but
      still dismal. Gynecologic small cell malignancies tend to show a better survival
      than similar histologies of other regions. However, of five reported cases of
      vulvar manifestation only one patient was disease-free at the time of publication
      with limited follow-up. CASE REPORT: The authors describe a case of locally
      advanced small cell vulva carcinoma infiltrating the anal sphincter and urethra
      with spread to inguinal lymph nodes treated by radiochemotherapy and regional
      hyperthermia. After three cycles of carboplatin/ etoposide, computed tomography
      and magnetic resonance imaging indicated only little regressive transformations
      but overall stable disease. Surgical options were excluded. Therefore, curative
      radiotherapy to a total dose of > 65 Gy to macroscopic tumor, chemotherapy with
      cisplatin weekly, and regional hyperthermia were performed. Acute severe toxicity
      was limited to skin reactions. Despite the disadvantageous situation with
      inguinal lymph node metastases and chemoresistance, the multimodal therapy
      yielded a 5-year disease-free survival. CONCLUSION: Thus, the trimodal regimen of
      radiochemotherapy plus regional hyperthermia offered a curative chance in spite
      of resistance to the standard chemotherapy for irresectable, locally advanced
      small cell carcinoma of the vulva. Therefore, this approach merits further
      evaluation for limited disease of EPSCC.

PMID- 20803182
TI  - Pattern of failure after helical tomotherapy in head and neck cancer.
AB  - BACKGROUND AND PURPOSE: Helical tomotherapy (HT, Hi-Art TomoTherapy((r))) is a
      recently developed radiation device delivering highly conformal dose with a
      rotational gantry resulting in more uniform target doses and better avoidance of
      organs at risk. Treatment failure patterns in head and neck cancer (HNC) patients
      treated with HT were analyzed. PATIENTS AND METHODS: 63 patients with a biopsy
      proven HNC were treated with HT. In patients with locoregional failure, the
      volume of failure (Vf) was contoured and co-registered with the initial planning
      computed tomography scan. With the use of dose-volume histogram (DVH) analysis,
      the Vf was classified as "in-field" (InF), "marginal" (MF) or "outside-field"
      (OutF), if >= 95%, 20-94%, and < 20% of Vf, respectively, were within the 95%
      isodose. RESULTS: Median follow-up time was 25 months (95% confidence interval
      19.4-28 months). 2-year overall survival, disease-free survival, and locoregional
      control were 66%, 54%, and 77%, respectively. 13 patients developed a
      locoregional failure (four local, eight regional, and one local and regional).
      After DVH analysis, there were ten InF and two MF recurrences as well as one OutF
      recurrence. CONCLUSION: Target delineation and coverage were adequate. The
      majority of locoregional failures were InF, i.e., in the high-dose region. Future
      work on dose escalation to the highest risk regions is recommended.

PMID- 20803183
TI  - Radiation therapy and internet - what can patients expect? homepage analysis of
      german radiotherapy institutions.
AB  - BACKGROUND: the internet as a source of medical information has emerged during
      the last years. There is a confusing amount of medical websites with a great
      diversity of quality. Websites of radiotherapy institutions could offer a safe
      and an easy-to-control way to assist patients' requests. MATERIAL AND METHODS:
      205 internet appearances of German radiotherapy institutions were analyzed in
      June 2009 (nonuniversity hospitals n = 108, medical practices n = 62, university
      hospitals n = 35). For the evaluation of each homepage verifiable criteria
      concerning basic information, service and medical issues were used. RESULTS: the
      quality of information published via internet by different radiotherapy
      institutions showed a large variety. Basic information like telephone numbers,
      operating hours, and direction guidance were provided in 96.7%, 40%, and 50.7%,
      respectively. 85% of the websites introduced the staff, 50.2% supplied photos and
      14% further information on the attending physicians. The mean amount of
      continuative links to other websites was 5.4, the mean amount of articles
      supplying medical information for patients summed up to 4.6. Medical practices
      and university hospitals had statistically significant more informative articles
      and links to other websites than nonuniversity hospitals. No statistically
      significant differences could be found in most other categories like service
      issues and basic information. CONCLUSION: internet presences of radiotherapy
      institutions hold the chance to supply patients with professional and
      individualized medical information. While some websites are already using this
      opportunity, others show a lack of basic information or of user-friendliness.

PMID- 20803184
TI  - A planning comparison of dynamic IMRT for different collimator leaf thicknesses
      with helical tomotherapy and RapidArc for prostate and head and neck tumors.
AB  - PURPOSE: A comparative analysis of the three most advanced intensity-modulated
      radiotherapy (IMRT) techniques currently commercially available was performed.
      Treatment plans made in rotational techniques (helical tomotherapy [HT] and
      RapidArc) were compared with sliding-window IMRT (dIMRT) on a conventional linear
      accelerator using different leaf thicknesses (2.5 mm, 5 mm, and 10 mm). The
      influence of the different planning techniques on the coverage of planning volume
      and sparing of organs at risk (OARs) was investigated. PATIENTS AND METHODS: Nine
      patients with localized prostate and nine patients with head and neck cancer were
      chosen for this study. Treatment planning was performed in Eclipse (Varian) and
      in Tomotherapy planning software. Treatment plans were compared according to
      target volume coverage and sparing OARs, as well as by conformity and homogeneity
      index. RESULTS: For both investigated tumor sites, the dosimetric effects of leaf
      widths between 2.5 mm, 5 mm and 10 mm were shown to be small in regard to target
      coverage. Tomotherapy plans had better target coverage (higher minimum dose). For
      prostate cancer, better sparing of bladder and rectum was achieved with RapidArc
      and dIMRT plans. For head and neck cancer, best sparing of parotid glands was
      achieved in HT plans. There was no significant difference (p > 0.05) in sparing
      of OARs between the dIMRT plans with different leaf widths neither for prostate
      cancer nor for head and neck cancer. CONCLUSION: For prostate and head and neck
      cases, all investigated IMRT techniques provide highly conformal treatment plans
      in terms of both target coverage and critical structure sparing.

PMID- 20803185
TI  - Intraoperative radiotherapy (IORT) with low-energy photons as a boost in patients
      with early-stage oral cancer with the indications for postoperative radiotherapy
      : treatment feasibility and preliminary results.
AB  - PURPOSE: To evaluate the feasibility and preliminary results of intraoperative
      radiotherapy (IORT) with low-energy photons as a boost in patients with early
      stage oral cancer with the indications for postoperative radiotherapy. PATIENTS
      AND METHODS: Between 2003 and 2006, 16 patients with early-stage cancer of mobile
      tongue (n = 10 [63%]) or floor of the mouth (n = 6 [37%]) treated at Maria
      Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice
      Branch, Poland, were evaluated for IORT boost with the INTRABEAM(r)System (Carl
      Zeiss Surgical GmbH; IORT-PRS) because of the high risk of local recurrence due
      to positive margins on frozen pathologic section. After tumor resection, the
      applicator was positioned in the tumor bed. The applicator's diameter (range: 1.5
      5 cm) was selected to encompass high-risk area of tumor recurrence. The dose (5
      Gy, 7 Gy, or 7.5 Gy) was applied according to tumor volume and bone proximity.
      External-beam radiotherapy (EBRT) was provided to the tumor bed in all patients
      (50 Gy) and to the nodal area, when needed. Toxicity and local tumor control were
      assessed. RESULTS: Median follow-up was 36 months. IORT did not increase acute
      mucosal reaction. Local tumor control was found in all cases. Early mucosal
      reaction did not exceed 3 according to the RTOG scale and healed in median time
      of 35 days after completion of EBRT. No late adverse effects were observed.
      CONCLUSION: This preliminary report has demonstrated the feasibility of IORT-PRS
      for patients with early oral cancer with the indications for postoperative
      radiotherapy. This method may be considered an alternative boost technique,
      although additional studies are needed to establish long-term results in a larger
      group of patients.

PMID- 20803186
TI  - A phase I/II study of altered fractionated IMRT alone for intermediate T-stage
      oropharyngeal carcinoma.
AB  - BACKGROUND AND PURPOSE: To prospectively assess the feasibility and efficacy of
      an accelerated and hyperfractionated intensity- modulated radiation therapy
      (IMRT) schedule for intermediate T-stage oropharyngeal cancer. PATIENTS AND
      METHODS: Patients with T3 or unfavorable T2 oropharyngeal squamous cell carcinoma
      were eligible; a three-dose level simultaneous integrated boost IMRT strategy was
      used, delivering 78, 69, and 60 Gy to gross disease, high-risk and low-risk
      target areas, respectively, in 60 twice daily fractions over 6 weeks. No
      sequential/concomitant systemic treatment or up-front radical surgery was
      allowed. Median follow-up is 41.7 months (range: 3.5-80.8 months). RESULTS: 25
      patients were treated from 11/2002 to 11/2005. 92% of the individual fractions
      were delivered as scheduled. Grade 3 mucosal and skin toxicity was 100% and 72%,
      respectively, none of which persisted beyond 12 weeks; a percutaneous endoscopic
      gastrostomy tube was temporarily placed in 60% of patients. The estimated
      locoregional progression-free, distant metastases-free, and overall survival
      rates at 3 years were 86.3% +/- 7.4%, 76.4% +/- 9.6%, and 70.0% +/- 9.6%,
      respectively. At the same time interval, the actuarial prevalence of grade 3+
      CTCAE v3.0 toxicity was 26.1%. CONCLUSION: While the routine clinical use of this
      exploratory schedule is discouraged, it may represent the basis for future
      developments.

PMID- 20803187
TI  - Clinical results of proton-beam therapy for locoregionally advanced esophageal
      cancer.
AB  - PURPOSE: To evaluate the efficacy and safety of proton-beam therapy for
      locoregionally advanced esophageal cancer. PATIENTS AND METHODS: The subjects
      were 51 patients with esophageal cancer who were treated between 1985 and 2005
      using proton beams with or without X-rays. All but one had squamous cell
      carcinoma. Of the 51 patients, 33 received combinations of X-rays (median 46 Gy)
      and protons (median 36 GyE) as a boost. The median total dose of combined X-rays
      and proton radiation for these 33 patients was 80 GyE (range 70-90 GyE). The
      other 18 patients received proton-beam therapy alone (median 79 GyE, range 62-98
      GyE). RESULTS: Treatment interruption due to radiation-induced esophagitis or
      hematologic toxicity was not required for any patient. The overall 5-year
      actuarial survival rate for the 51 patients was 21.1% and the median survival
      time was 20.5 months (95% confidence interval 10.9-30.2). Of the 51 patients, 40
      (78%) showed a complete response within 4 months after completing treatment and
      seven (14%) showed a partial response, giving a response rate of 92% (47/51). The
      5-year local control rate for all 51 patients was 38.0% and the median local
      control time was 25.5 months (95% confidence interval 14.6-36.3). CONCLUSION: The
      results suggest that proton-beam therapy is an effective treatment for patients
      with locally advanced esophageal cancer. Further studies are required to
      determine the optimal total dose, fractionation schedules, and best combination
      of proton therapy with chemotherapy.

PMID- 20803188
TI  - [The psychopathology of ego disturbances: history and phenomenology].
AB  - The phenomena which Kurt Schneider grouped together to form the ego disturbances
      have always been of particular diagnostic relevance for schizophrenia. While
      little importance was historically attached to accurately describing and
      distinguishing psychopathological symptoms, Karl Jaspers' and Kurt Schneider's
      descriptive psychopathology aims to draw a sharp yet differentiated distinction
      between psychotic and non-psychotic disorders at the symptom level. New
      developments in phenomenology including aspects of symptom development are
      presented. The depersonalization experience is focused on as a transitional
      phenomenon which is distinguishes from neurotic depersonalization through a
      disturbed sense of mineness. The ego disturbances indicate that disturbed
      mineness can be seen as the common denominator of first-rank symptoms of
      schizophrenia.

PMID- 20803189
TI  - From authority recommendations to fact-sheets--a future for guidelines.
AB  - ADA/EASD recommendations and diabetes expert consensus statements are not
      evidence-based. Reform of guideline development is urgently needed. Overriding
      governance and composition of the guideline committee is a key problem.
      Methodologists without important conflicts of interest should lead the
      development process and have primary responsibility. The rating of the quality of
      evidence should be separated from making the recommendations, transparency has to
      be increased and conflicts of interest must be tackled. Patient needs are not yet
      met in guidelines. Patients increasingly demand concise, easy-to-read summaries
      of the benefits and risks of medicines together with more comprehensive
      scientific data. However, patient participation in individual decision making is
      not considered in guidelines. Guidelines do not provide the information necessary
      for informed or shared decision making. Study fact-sheets and drug facts boxes
      should be included in practice guidelines. It is timely to consider patient needs
      from the outset of the development of future guidelines.

PMID- 20803190
TI  - Biomedical risk factors for decreased cognitive functioning in type 1 diabetes:
      an 18 year follow-up of the Diabetes Control and Complications Trial (DCCT)
      cohort.
AB  - AIMS/HYPOTHESIS: In patients with type 1 diabetes, there has been concern about
      the effects of recurrent hypoglycaemia and chronic hyperglycaemia on cognitive
      function. Because other biomedical factors may also increase the risk of
      cognitive decline, this study examined whether macrovascular risk factors
      (hypertension, smoking, hypercholesterolaemia, obesity), sub-clinical
      macrovascular disease (carotid intima-media thickening, coronary calcification)
      and microvascular complications (retinopathy, nephropathy) were associated with
      decrements in cognitive function over an extended time period. METHODS: Type 1
      diabetes patients (n = 1,144) who had completed a comprehensive cognitive test
      battery at entry into the Diabetes Control and Complications Trial were re
      assessed at a mean of 18.5 (range: 15-23) years later. Univariate and
      multivariable models examined the relationship between cognitive change and the
      presence of micro- and macrovascular complications and risk factors. RESULTS:
      Univariate modelling showed that smoking history was modestly associated with
      decrements in learning, memory, spatial information-processing and psychomotor
      efficiency; hypertension was associated with only psychomotor slowing.
      Multivariable modelling demonstrated that HbA(1c) level, and retinal and renal
      complications were each independently associated with decrements in psychomotor
      efficiency. In contrast, no macrovascular risk factors were significant after
      correcting for multiple comparisons. No interactions were found between these
      predictors and sex, severe hypoglycaemic events or presence of the APOE epsilon4
      allele. CONCLUSIONS/INTERPRETATION: In relatively healthy, middle-aged adults
      with type 1 diabetes who had been followed for an average of 18.5 years, long
      term metabolic control and microvascular factors are independently associated
      with a decline in cognitive function specifically affecting measures of
      psychomotor efficiency. TRIAL REGISTRATION: ClinicalTrials.gov NCT00360893.

PMID- 20803191
TI  - Oscillations of cardiac wave length and proarrhythmia.
AB  - Drug-induced action potential duration (APD) prolongation was first proposed to
      be antiarrhythmic, but is now widely presumed to be torsadogenic. To elucidate
      this paradox, we tested the effect of APD upon liability for torsade de pointes.
      In addition, torsadogenicity is commonly associated with disturbances of
      repolarization, but at least in theory, it could also result from disturbances of
      conduction. These possibilities were tested in female rabbit hearts. Dofetilide,
      ATX II, and sodium channel blockers that did not prolong the action potential
      duration were used to modulate the APD and induce disturbances of conduction and
      disturbances of repolarization. Torsadogenicity could be induced by dofetilide
      and ATX II starting at normal APD (210 ms), reaching a peak incidence around a
      doubling of APD (400 to 450 ms), to then sharply decline with further APD
      prolongation, until torsade de pointes disappeared above 725 ms. Early
      afterdepolarizations (EAD) were regular triggers for torsade de pointes; while
      most of the EADs occurred in the plateau range, their incidence declined with
      repolarization but their potential for torsadogenicity increased. Sodium channel
      blockers that shorten the APD, even when devoid of hERG blocking properties, can
      yield torsade de pointes. Torsade de pointes can occur at normal, prolonged, and
      shortened APD, so that QT prolongation is an incomplete predictor of
      torsadogenicity. Torsade de pointes can result not only from disturbances of
      repolarization but also from disturbances of conduction.

PMID- 20803193
TI  - A methylation-stimulated DNA machine: an autonomous isothermal route to
      methyltransferase activity and inhibition analysis.
AB  - The operation of DNA nanomachines is generally triggered by either conformational
      changes of DNA nanostructure or external environmental stimuli. In the present
      study, we demonstrate an alternative driving force, DNA methylation, to stimulate
      DNA machine operation. DNA methylation changes neither DNA sequence and
      conformation nor external environment, however, blocks its cleavage by
      corresponding methylation-sensitive restriction endonuclease. We thus designed a
      strand displacement amplification DNA machine, which could be stimulated upon DNA
      methylation and then autonomously generates accumulated amounts of peroxidase
      mimicking DNAzyme signaling machine products in an isothermal manner. The machine
      product DNAzyme could catalyze the H(2)O(2)-mediated oxidation of 2,2'-azino
      bis(3-ethylbenzo thiazoline-6-sulfonic acid) (ABTS(2-)) to a colored product
      ABTS(.-). This methylation-stimulated DNA machine was further used as a
      colorimetric assay for analysis of methyltransferases activities and screening of
      methylation inhibitors. As compared with classical methylation assay, this facile
      isothermal DNA machine avoids the introduction of methylation-specific polymerase
      chain reaction and radioactive labels, which might be employed as an effective
      tool for DNA methylation analysis.

PMID- 20803192
TI  - The Arg16Gly-beta(2)-adrenoceptor single nucleotide polymorphism: exercise
      capacity and survival in patients with end-stage heart failure.
AB  - Heart failure (HF) is characterized by impaired myocardial beta-adrenergic signal
      transduction. Single nucleotide polymorphisms (SNPs) within the beta(1)-
      (Ser49Gly, Arg389Gly) and beta(2)-adrenoceptor (Arg16Gly, Gln27Glu, Thr164Ile)
      have been associated with alterations in adrenoceptor (AR) function sensitivity
      in vitro and in vivo and possibly contribute to HF progression. The present study
      evaluated the relation of those SNPs to morbidity and mortality in patients with
      end-stage HF. A total of 226 patients with end-stage HF (ejection fraction <=35%)
      were genotyped for the two beta(1)AR SNPs and the three beta(2)AR SNPs. Outcome
      (death, heart transplantation (HTX)) was determined from May 2003 to June 2004.
      Heart rate, systolic and diastolic blood pressure, and peak oxygen uptake were
      measured during graded treadmill exercise. Left ventricular end-diastolic and end
      systolic diameters, ejection fraction, and fractional shortening at rest were
      measured using two-dimensional echocardiography. Minor allele frequencies were
      0.12 for Gly49 and 0.27 for Gly389 (beta(1)AR) and 0.37 for Arg16, 0.43 for Glu27
      and 0.01 for Ile164 (beta(2)AR). During follow-up, 45 patients died (20%), and 27
      patients underwent HTX (12%). No significant differences in the incidence or in
      the time-to-endpoint of death and HTX between genotypes of the different SNPs
      within the beta(1)- and beta(2)AR were detected. However, patients carrying the
      Arg16-beta(2)AR tended to have lower exercise capacity and a higher probability
      for death/HTX within 45 months (survival proportion 46%) than patients carrying
      the Gly16Gly-beta(2)AR (survival proportion 64%). In conclusion, the Arg16Gly
      beta(2)AR might impact on exercise capacity and outcome in end-stage heart
      failure.

PMID- 20803194
TI  - Arsenic-induced protein phosphorylation changes in HeLa cells.
AB  - Arsenic is well documented as a chemotherapeutic agent capable of inducing cell
      death while at the same time is considered a human carcinogen and an
      environmental contaminant. Although arsenic toxicity is well known and has formed
      an impressive literature over the time, little is known about how its effects are
      exerted at the proteome level. Protein phosphorylation is an important post
      translational modification involved in the regulation of cell signaling and
      likely is altered by arsenic treatment. Despite the importance of phosphorylation
      for many regulatory processes in cells, the identification and characterization
      of phosphorylation, as effected by arsenic through mass spectrometric detection,
      are not fully studied. Here, we identify phosphorylated proteins, which are
      related to post-translational modifications after phenylarsine oxide (PAO)
      inoculation to HeLa cells. PAO was chosen because of its high cytotoxicity,
      measured earlier in these labs. In this study, size exclusion chromatography
      coupled to inductively coupled plasma mass spectrometry (SEC-ICP-MS) is used to
      establish several molecular weight fractions with phosphorylated proteins by
      monitoring (31)P signal vs. time via ICP-MS. SEC-ICP-MS fractions are collected
      and then separated by the nano-LC-CHIP/ITMS system for peptide determination.
      Spectrum Mill and MASCOT protein database search engines are used for protein
      identification. Several phosphorylation sites and proteins related to post
      translational modifications are also identified.

PMID- 20803195
TI  - Stacking and determination of phenazine-1-carboxylic acid with low pKa in soil
      via moving reaction boundary formed by alkaline and double acidic buffers in
      capillary electrophoresis.
AB  - As shown herein, a normal moving reaction boundary (MRB) formed by an alkaline
      buffer and a single acidic buffer had poor stacking to the new important plant
      growth promoter of phenazine-1-carboxylic acid (PCA) in soil due to the leak
      induced by its low pK(a). To stack the PCA with low pK(a) efficiently, a novel
      stacking system of MRB was developed, which was formed by an alkaline buffer and
      double acidic buffers (viz., acidic sample and blank buffers). With the novel
      system, the PCA leaking into the blank buffer from the sample buffer could be
      well stacked by the prolonged MRB formed between the alkaline buffer and blank
      buffer. The relevant mechanism of stacking was discussed briefly. The stacking
      system, coupled with sample pretreatment, could achieve a 214-fold increase of
      PCA sensitivity under the optimal conditions (15 mM (pH 11.5) Gly-NaOH as the
      alkaline buffer, 15 mM (pH 3.0) Gly-HCl-acetonitrile (20%, v/v) as the acidic
      sample buffer, 15 mM (pH 3.0) Gly-HCl as the blank buffer, 3 min 13 mbar
      injection of double acidic buffers, benzoic acid as the internal standard, 75 MUm
      i.d. * 53 cm (44 cm effective length) capillary, 25 kV and 248 nm). The limit of
      detection of PCA in soil was decreased to 17 ng/g, the intra-day and inter-day
      precision values (expressed as relative standard deviations) were 3.17-4.24% and
      4.17-4.87%, respectively, and the recoveries of PCA at three concentration levels
      changed from 52.20% to 102.61%. The developed method could be used for the
      detection of PCA in soil at trace level.

PMID- 20803196
TI  - Structure elucidation of the thermal degradation products of the nucleotide
      cofactors NADH and NADPH by nano-ESI-FTICR-MS and HPLC-MS.
AB  - Redox cofactors like NADH and NADPH are essential for the catalytic activity of
      several oxidoreductases. Here, we describe a comparative study of the thermal
      degradation products of both cofactors in the dry and liquid states. The
      degradation products were first separated, detected, and quantified by high
      performance liquid chromatography (HPLC). Subsequently, selected main fractions
      were investigated by nanoelectrospray ionization-Fourier transform ion cyclotron
      resonance mass spectrometry (MS). Additionally, HPLC-MS was used to elucidate the
      structure of all degradation products. From these data, degradation pathways for
      both the liquid and the solid states were elucidated. Thermal degradation in
      water is significantly faster compared to degradation in the solid state.
      Hydrolysis and oxidative ring opening of the reduced nicotinamide adenine
      dinucleotide (phosphate) were shown to be the main reaction paths. Surprisingly,
      no significant differences were observed between the degradation of both
      cofactors in solution and in the solid state. Our results demonstrate that the
      stability of both cofactors is not limiting at moderate temperatures if they are
      used in the dry state (e.g., solid/gas catalysis). Significant degradation of dry
      cofactors was only observed under conditions, which are usually not appropriate
      for biocatalysis (>95  degrees C). Besides, the situation is completely different
      in solution where degradation is already observed at moderate temperatures.

PMID- 20803197
TI  - Total internal reflection ellipsometry as a label-free assessment method for
      optimization of the reactive surface of bioassay devices based on a
      functionalized cycloolefin polymer.
AB  - We report a label-free optical detection technique, called total internal
      reflection ellipsometry (TIRE), which can be applied to study the interactions
      between biomolecules and a functionalized polymer surface. Zeonor (ZR), a
      cycloolefin polymer with low autofluorescence, high optical transmittance and
      excellent chemical resistance, is a highly suitable material for optical
      biosensor platforms owing to the ease of fabrication. It can also be modified
      with a range of reactive chemical groups for surface functionalization. We
      demonstrate the applications of TIRE in monitoring DNA hybridization assays and
      human chorionic gonadotrophin sandwich immunoassays on the ZR surface
      functionalized with carboxyl groups. The Psi and Delta spectra obtained after the
      binding of each layer of analyte have been fitted to a four-layer ellipsometric
      model to quantitatively determine the amount of analytes bound specifically to
      the functionalized ZR surface. Our proposed TIRE technique with its very low
      analyte consumption and its microfluidic array format could be a useful tool for
      evaluating several crucial parameters in immunoassays, DNA interactions,
      adsorption of biomolecules to solid surfaces, or assessment of the reactivity of
      a functionalized polymer surface towards a specific analyte.

PMID- 20803198
TI  - Controlling the invasive diatom Didymosphenia geminata: an ecotoxicity assessment
      of four potential biocides.
AB  - In 2004, an invasive mat-forming freshwater diatom, Didymosphenia geminata
      (didymo), was found in New Zealand causing concern with regard to potential
      consequences for local freshwater ecosystems. A four-stage research program was
      initiated to identify methods to control D. geminata. This article reports the
      results of Stage 2, in which four potential control compounds [GemexTM (a
      chelated copper formulation), EDTA, Hydrothol(r)191, and Organic InterceptorTM (a
      pine oil formulation)] selected in Stage 1 were evaluated for their biocidal
      efficacy on D. geminata and effects on non-target organisms using both artificial
      stream and laboratory trials. Artificial stream trials evaluated the mortality
      rates of D. geminata and fishes to three concentrations of the four biocides,
      whereas laboratory toxicity trials tested the response of green alga and
      cladocera to a range of biocide concentrations and exposure times. In artificial
      stream trials, Gemex and Organic Interceptor were the most effective biocides
      against D. geminata for a number of measured indices; however, exposure of fishes
      to Organic Interceptor resulted in high mortality rates. Laboratory toxicity
      testing indicated that Gemex might negatively affect sensitive stream
      invertebrates, based on the cladoceran sensitivity at the proposed river control
      dose. A decision support matrix evaluated the four biocides based on nine
      criteria stipulated by river stakeholders (effectiveness, non-target species
      impacts, stalk removal, degradation profile, risks to health and safety, ease of
      application, neutralization potential, cost, and local regulatory requirements)
      and Gemex was identified as the product warranting further refinement prior to an
      in-river trial.

PMID- 20803199
TI  - Hepatic element concentrations of lesser scaup (Aythya affinis) during spring
      migration in the upper Midwest.
AB  - High concentrations of some hepatic elements might be contributing to the decline
      of the continental lesser scaup (Aythya affinis) population. We evaluated hepatic
      element concentrations of male and female lesser scaup collected from the upper
      Midwest (Iowa, Minnesota, North Dakota, and South Dakota) during the 2003 and
      2004 spring migrations. We measured concentrations of 24 elements in livers of
      117 lesser scaup. We found that only selenium concentrations were at levels (>3.0
      MUg/g wet weight [ww)]) proposed to adversely affect reproduction. Approximately
      49% of females (n = 61) had individual hepatic concentrations >3.0 MUg/g ww
      selenium (Se). Our observed hepatic concentration of Se was similar to that
      reported in lesser scaup collected from the mid-continental United States but
      less than Se concentrations reported from the Great Lakes region. We found that
      the liver cadmium (Cd) concentration for males was significantly higher than that
      for females. Gender differences in hepatic Cd concentrations have not been
      previously reported for lesser scaup, but Cd is known to have negative impacts on
      male reproduction. Our results indicate that lesser scaup migrating through the
      upper Midwest in spring have elevated Se levels and that males carry a
      significantly greater Cd burden than females. Moreover, elemental concentrations
      might be high enough to affect reproduction in both male and female lesser scaup,
      but controlled laboratory studies are needed to adequately assess the effects of
      Se and Cd on lesser scaup reproduction.

PMID- 20803200
TI  - Anomalous right coronary artery arising from the pulmonary artery in a 36-year
      old woman: diagnosis by coronary computed tomographic angiography.

PMID- 20803201
TI  - Hip fracture after radiofrequency ablation therapy for bone tumors: two case
      reports.
AB  - Radiofrequency ablation (RFA) has become a valuable therapeutic modality in
      cancer treatment over the last decade. In orthopedic surgery, RFA is used for the
      treatment of benign bone tumors and bone metastases. Complications are rare and,
      to our knowledge, bone fracture as a complication due solely to RFA has not been
      reported to date. In this report we describe two patients with a fracture in the
      calcar region of the femur as a complication of RFA treatment for bone
      malignancies. Since RFA is applied increasingly often, it is important to report
      this risk of fracture as a complication of treatment of lesions in the femoral
      calcar.

PMID- 20803202
TI  - Derivation of a T2-weighted MRI total colonic inflammation score (TCIS) for
      assessment of patients with severe acute inflammatory colitis-a preliminary
      study.
AB  - OBJECTIVE: To derive an MRI score for assessing severity, therapeutic response
      and prognosis in acute severe inflammatory colitis. METHODS: Twenty-one patients
      with acute severe colitis underwent colonic MRI after admission and again (n =
      16) after median 5 days of treatment. Using T2-weighted images, two radiologists
      in consensus graded segmental haustral loss, mesenteric and mural oedema, mural
      thickness, and small bowel and colonic dilatation producing a total colonic
      inflammatory score (TCIS, range 6-95). Pre- and post-treatment TCIS were
      compared, and correlated with CRP, stool frequency, and number of inpatient days
      (therapeutic response marker). Questionnaire assessment of patient worry,
      satisfaction and discomfort graded 1 (bad) to 7 (good) was administered RESULTS:
      Admission TCIS correlated significantly with CRP (Kendall's tau=0.45, 95%
      confidence interval [CI] 0.11-0.79, p = 0.006), and stool frequency (Kendall's
      tau 0.39, 95% CI 0.14-0.64, p = 0.02). TCIS fell after treatment (median [22
      range 15-31]) to median 20 [range 8-25], p = 0.01. Admission TCIS but not CRP or
      stool frequency was correlated with length of inpatient stay (Kendall's tau 0.40,
      95% CI 0.11-0.69, p = 0.02). Patients reported some discomfort (median score 4)
      during MRI. CONCLUSIONS: MRI TCIS falls after therapy, correlates with existing
      markers of disease severity, and in comparison may better predict therapeutic
      response.

PMID- 20803203
TI  - Iodine contrast iso-attenuating with diagnostic gadolinium doses in CTA and
      angiography results in ultra-low iodine doses. A way to avoid both CIN and NSF in
      azotemic patients?
AB  - OBJECTIVES: To establish iodine (I) contrast medium (CM) doses iso-attenuating
      with gadolinium (Gd) CM doses regarded diagnostic in CTA and percutaneous
      catheter-angiography/vascular interventions (PCA/PVI) in azotemic patients.
      METHODS: CT Hounsfield units (HU) were measured in 20-mL syringes containing
      0.01/0.02,/0.05/0.1 mmol/mL of iodine or gadolinium atoms and placed in phantoms.
      Relative contrast were measured in 20-mL syringes filled with iohexol at
      35/50/70/90/110/140 mg I/mL and 0.5 M gadodiamide using radiofluoroscopy (RF),
      digital radiography (DX) and x-ray angiography (XA) systems. Clinical doses of Gd
      CM at CTA/PCA/PVI were reviewed. RESULTS: At CT 91-116 and 104-125 mg I/mL in the
      chest and abdominal phantoms, respectively, were iso-attenuating with 0.5 M Gd at
      80-140 kVp. At RF/DX/XA systems 35-90 mg I/mL were iso-attenuating with 0.5 M
      gadodiamide at 60-115 kVp. Clinically, 60 mL 91-125 mg I/mL (5.5-7.5 gram-iodine)
      at 80-140 kVp CTA and 60 mL of 35-90 mg I/mL (2.1-5.4 gram-iodine) at 60-115 kVp
      PCA/PVI would be iso-attenuating with 60 mL 0.5 M Gd-CM (=0.4 mmol Gd/kg in a 75
      kg person). CONCLUSIONS: Meticulous examination technique and judicious use of
      ultra-low I-CM doses iso-attenuating with diagnostic Gd-CM doses in CTA and
      PCA/PVI may minimise the risk of nephrotoxicity in azotemic patients, while there
      is no risk of NSF.

PMID- 20803204
TI  - Visual coverage and scanning behavior in two corvid species: American crow and
      Western scrub jay.
AB  - Inter-specific differences in the configuration of avian visual fields and degree
      of eye/head movements have been associated with foraging and anti-predator
      behaviors. Our goal was to study visual fields, eye movements, and head movements
      in two species of corvids: American crow (Corvus brachyrhynchos) and Western
      scrub jay (Aphelocoma californica). American crows had wider binocular overlap,
      longer vertical binocular fields, narrower blind areas, and higher amplitude of
      eye movement than Western scrub jays. American crows can converge their eyes and
      see their own bill tip, which may facilitate using different foraging techniques
      (e.g., pecking, probing) and manufacturing and handing rudimentary tools. Western
      scrub jays had a higher head movement rate than American crows while on the
      ground, and the opposite between-species difference was found when individuals
      were perching. Faster head movements may enhance the ability to scan the
      environment, which may be related to a higher perceived risk of predation of
      Western scrub jays when on the ground, and American crows when perching. The
      visual field configuration of these species appears influenced mostly by foraging
      techniques while their scaning behavior, by predation risk.

PMID- 20803205
TI  - Malnutrition as a predictor of poor postoperative outcomes in gynecologic cancer
      patients.
AB  - PURPOSE: Poor nutritional status has been associated with increased postoperative
      morbidity and mortality in surgical patients. The purpose of this study is to
      evaluate if decreased nutritional parameters correlate with increased
      postoperative complications regardless of other risk factors in the gynecologic
      cancer patient. METHODS: A retrospective chart review was performed among women
      who underwent surgical management for gynecologic malignancies from October 2006
      to June 2008. Variables included age, race, medical comorbidities, cancer
      type/stage, preoperative albumin, absolute lymphocyte count (ALC), and body mass
      index (BMI), estimated blood loss (EBL), intraoperative blood transfusion (BT),
      intraoperative or postoperative complications, intensive care unit (ICU)
      admissions, hospital readmissions, reoperations, and cancer recurrence. RESULTS:
      Three hundred gynecologic oncology patients with preoperative nutritional
      parameters were included in the study. Decreased albumin was significantly
      associated with more postoperative complications (p < 0.001), hospital
      readmissions (p = 0.01), reoperations (p = 0.03), ICU admissions (p < 0.001), and
      cancer recurrence (p < 0.001). Decreased ALC and BMI preoperatively was also
      significantly associated with higher incidence of cancer recurrence (p = 0.01, p
      = 0.01). Surgical cases involving increased EBL (p = 0.01, p < 0.001) and more BT
      (p < 0.001, p < 0.001) had significantly more postoperative complications and
      more ICU admissions. Multivariable logistic regression found preoperative albumin
      to be an independent predictor of increased postoperative complications.
      CONCLUSIONS: Decreased albumin is significantly associated with more
      postoperative complications, hospital readmissions, reoperations, ICU admissions,
      and cancer recurrence. This nutritional parameter is an important predictor of
      postoperative morbidity and mortality. Thus, it is important to assess
      nutritional status preoperatively and offer nutritional support or alternate
      treatment options if necessary.

PMID- 20803206
TI  - E-cadherin as a prognostic marker in human serous carcinomas of the ovary: an
      immunohistochemical analysis.
AB  - INTRODUCTION: Ovarian cancer is a gynecologic cancer with a high mortality rate,
      demonstrating the need for effective and reliable tumor markers during the
      staging and treatment processes. METHODS: Expression of E-cadherin was
      immunohistochemically analyzed in 100 ovarian cancer tissue samples. RESULTS: A
      significant association of E-cadherin expression with histological grading (p =
      0.001) and surgical stage (p = 0.020) could be demonstrated. However, the
      staining intensity of E-cadherin was not significantly associated with
      progression-free, cause-specific survival or overall survival in serous ovarian
      carcinomas. CONCLUSION: The E-cadherin expression was associated with FIGO
      surgical staging and histological differentiation in serious ovarian carcinomas,
      suggesting a substantial role in the carcinogenesis of serous ovarian carcinomas.
      However, although patients with a strong E-cadherin staining intensity had a
      better prognosis, no statistical significant differences could be observed.
      Therefore, E-cadherin might not be a useful prognostic tumor marker in serous
      ovarian carcinomas.

PMID- 20803207
TI  - The prognostic and predictive value of CA-125 regression during neoadjuvant
      chemotherapy for advanced ovarian or primary peritoneal carcinoma.
AB  - PURPOSE: To assess the significance of CA-125 regression as a prognostic
      indicator and predictor of optimal cytoreduction at interval debulking surgery
      (IDS) in women with ovarian or primary peritoneal carcinoma receiving neoadjuvant
      chemotherapy (NAC). METHODS: 63 women treated between 2004 and 2007 with
      neoadjuvant platinum-based chemotherapy followed by IDS were studied
      retrospectively. Pre-operative CA-125 values were used to calculate a regression
      coefficient (CA-125r) using exponential regression analysis. Outcome endpoints
      were overall survival (OS), time to CA-125 progression (TTC) by Rustin criteria
      and time to second-line treatment (TTS). RESULTS: Women with a CA-125 half-life
      greater than 18 days had a significantly worse OS compared to those with a half
      life less than 12 days on univariate testing (HR 3.34, 95% CI 1.25-8.94, p =
      0.017). On multivariable analysis, CA-125r was an independent predictor of OS [HR
      1.18 (per 0.01 increase in CA-125r), 95% CI 1.01-1.40, p = 0.043]. CA-125r was
      independently predictive of TTC and TTS (HR 1.17, p ~ 0.03 for each). CA-125r was
      also predictive of achieving optimal cytoreduction at IDS (AUC 0.756, p < 0.001).
      CONCLUSIONS: CA-125 regression rate during pre-operative NAC is of independent
      prognostic value. CA-125 regression rate strongly predicts for optimal
      cytoreduction.

PMID- 20803208
TI  - Antepartum intracranial hemorrhage due to unrecognized unilateral moyamoya
      disease: a case report.
AB  - PURPOSE: Moyamoya (meaning a "hazy puff of smoke" in Japanese) disease is a rare
      cerebrovascular occlusive disease. Moyamoya disease may become symptomatic for
      the first time during pregnancy. We report a case of antepartum intracranial
      hemorrhage due to unrecognized unilateral moyamoya disease, which was
      subsequently diagnosed as HELLP syndrome during the postpartum period. STUDY
      DESIGN: A case report of a 29-year-old Japanese primigravida who was transported
      to our hospital at 39 weeks of gestation because of sudden loss of consciousness
      and left hemiplegia. On arrival, her blood pressure was 143/94 mmHg with 1+
      proteinuria by dipstick. Brain computed tomography revealed a right putaminal
      hemorrhage with intraventricular hemorrhage. The patient delivered a neonate by
      emergency cesarean section, and an intracranial hematoma was subsequently
      evacuated. Approximately 3 h postoperatively, she was diagnosed with HELLP
      syndrome and the following were initiated: IV magnesium sulfate, antihypertensive
      agents, and transfusion of 10 units of platelets. Angiographic findings were
      consistent with unilateral moyamoya disease. CONCLUSIONS: Moyamoya disease is a
      rare entity that must be considered in the differential diagnosis of hemorrhagic
      stroke during pregnancy. It is important to perform careful monitoring and
      adequate management with cooperation between obstetricians and other specialists
      when serious complications arise.

PMID- 20803209
TI  - Treatment of recurrent vulvar Paget disease with imiquimod cream: a case report
      and review of the literature.
AB  - INTRODUCTION: Extra-mammary Paget disease is one of the rare neoplastic
      conditions of the skin. The most common site of involvement is the vulva and
      presents itself with erythematous plaques. Surgery is the most important
      treatment option. In the recent years, there are publications of the topical use
      of imiquimod cream in extra-mammary cutaneous Paget disease. We report the case
      of a woman with recurrent vulvar Paget disease, who underwent successful
      treatment with imiquimod cream. We also review the reports of other patients with
      vulvar Paget disease who were treated with topical imiquimod cream. CASE REPORT:
      A 65-year-old woman presented to the Oncology Outpatient Clinic with an itchy
      lesion in her vulva for 2 years. In the gynecologic examination, a hyperkeratotic
      erythematous lesion was found starting from the right labium to involve clitoris,
      with a size of 4 * 3 cm. Pathology result was reported as Paget disease. She was
      operated and wide vulvar excision was performed with a safety margin of 2 cm.
      Then recurrence two times occurred. Because she refused surgery, imiquimod cream
      5% was applied for treatment. CONCLUSION: Imiquimod cream is an effective and
      safe therapeutic agent for both primary and recurring vulvar Paget disease.

PMID- 20803210
TI  - The psychosocial impact of vesico-vaginal fistula in Niger.
AB  - PURPOSE: To explore the psycho-social impact of vesico-vaginal fistula (VVF) on
      women in Niger. STUDY DESIGN: We conducted a qualitative study on 21 women in
      convalescence at the DIMOL Reproductive Health Center in Niamey, Niger, in 2008
      and 2009. The women had undergone 1-3 fistula repair operations and all had
      stillborn infants. RESULTS: Women reported many psychological consequences of VVF
      including depression, feelings of shame, and loneliness. Others reported feeling
      devalued as a woman and wanting to end their lives. Social consequences of
      fistula reported by these women included rejection from society, isolation,
      rejection from husband and/or divorce. Almost half of the women reported of
      having lost their social network and support as a result of the fistula. Women
      with VVF were deemed unworthy, and their illness was often attributed to some
      fault of their own. CONCLUSIONS: Our findings support the notion that socio
      economic factors, though they certainly contribute to obstetric fistula, are not
      the primary reason for fistula, particularly in Niger. Fistula is a direct result
      of lack of access to skilled birth attendants and emergency obstetric care.

PMID- 20803211
TI  - High squamous intraepithelial lesion and cancer of lower genital tract in women
      with anogenital warts.
AB  - PURPOSE: The aim of this paper was to determine the incidence of high-grade
      squamous intraepithelial lesion (HSIL) and cancer of lower genital tract in
      patients with anogenital warts and their treatment. METHODS: Between 1 September
      1988 and 30 June 1994, 221 consecutive women with anogenital warts were
      prospectively examined in the colposcopy outpatient clinic. In 2004, the same
      group of patients was re-examined. RESULTS: There were abnormal cytological
      findings in 111 (50.2%) patients; 31 patients (14.0%) had HSIL, and 6 of them
      (2.7%) had cancer. There were abnormal colposcopic findings in 152 (68.8%) women;
      78 women (35.3%) had abnormal histological findings. In the histological
      findings, HSIL was found in 41 (18.5%) women and cancer in 6 (2.7%). CONCLUSION:
      In spite of the fact that anogenital warts are caused by HPV types of low
      oncogenic risk (6/11), there is an increased incidence of HSIL and cancer in
      these women. Therefore, women with anogenital warts belong to an increased risk
      group regarding the cancer of lower genital tract, especially if they are
      associated with HPV types of a high oncogenic risk.

PMID- 20803212
TI  - Recurrent tumefactive demyelination without evidence of multiple sclerosis or
      brain tumour.

PMID- 20803213
TI  - Magnesium treatment for patients with refractory status epilepticus due to POLG1
      mutations.
AB  - Mutations in the gene encoding of the catalytic subunit of mtDNA polymerase gamma
      (POLG1) can cause typical Alpers' syndrome. Recently, a new POLG1 mutation
      phenotype was described, the so-called juvenile-onset Alpers' syndrome. This
      POLG1 mutation phenotype is characterized by refractory epilepsy with recurrent
      status epilepticus and episodes of epilepsia partialis continua, which often
      necessitate admission to the intensive care unit (ICU) and pose an important
      mortality risk. We describe two previously healthy unrelated teenage girls, who
      both were admitted with generalized tonic-clonic seizures and visual symptoms
      leading to a DNA-supported diagnosis of juvenile-onset Alpers' syndrome. Despite
      combined treatment with anti-epileptic drugs, both patients developed status
      epilepticus requiring admission to the ICU. Intravenous magnesium as anti
      convulsant therapy was initiated, resulting in clinical and neurophysiological
      improvement and rapid extubation of both patients. Treating status epilepticus in
      juvenile-onset Alpers' syndrome with magnesium has not been described previously.
      Given the difficulties encountered while treating epilepsy in patients with this
      syndrome, magnesium therapy might be considered.

PMID- 20803214
TI  - Biological monitoring of exposure to di(2-ethylhexyl) phthalate in six French
      factories: a field study.
AB  - OBJECTIVE: The aim of this study was to assess, by biological monitoring,
      workers' exposure to di(2-ethylhexyl) phthalate (DEHP) in the flexible-PVC
      industry in France to provide additional occupational exposure data, which are
      particularly scarce. METHOD: Over 5 days of pre-and post-shift sampling, three
      urinary metabolites of DEHP, mono (2-ethylhexyl) phthalate (MEHP), mono (5
      carboxy-2-ethylpentyl) phthalate (5cx-MEPP) and 2-ethylhexanoic acid (2-EHA) were
      quantified in 62 workers and 29 controls from six factories. Analyses were
      performed by high-performance liquid chromatography with tandem mass spectrometry
      (HPLC-MS/MS) after on-line extraction. RESULTS: Median concentrations of the pre-
      and post-shift urinary samples in the exposed workers were 12.6 and 28.7 MUg/l
      for MEHP, 38.6 and 84.4 MUg/l for 5cx-MEPP and 20.4 and 70.6 MUg/l for 2-EHA,
      respectively. In the controls, the corresponding values were 4.8 and 4.7 MUg/l
      for MEHP, 15.1 and 12.4 MUg/l for 5cx-MEPP and 21.8 and 20.5 MUg/l for 2-EHA,
      respectively. There was a significant increase (Mann-Whitney U-test, P < 0.05) of
      post-shift excretion in the exposed workers versus the unexposed controls and in
      the post-shift versus pre-shift concentrations only in the exposed workers.
      Values of 250 and 500 MUg/l (100 and 280 MU/g creatinine) for MEHP and 5cx-MEPP,
      respectively, are proposed as guidance values. CONCLUSION: There is clear
      evidence of occupational exposure of workers in these factories. The guideline
      values proposed should prevent high exposures in the soft PVC industry,
      particularly in factories where DEHP compounds or plastisols are employed. An
      epidemiological survey is needed to complete the DEHP risk assessment.

PMID- 20803215
TI  - Inhibition of phospholipase C disrupts cytoskeletal organization and gravitropic
      growth in Arabidopsis roots.
AB  - The phospholipase protein superfamily plays an important role in hormonal
      signalling and cellular responses to environmental stimuli. There is also growing
      evidence for interactions between phospholipases and the cytoskeleton. In this
      report we used a pharmacological approach to investigate whether inhibiting a
      member of the phospholipase superfamily, phospholipase C (PLC), affects
      microtubules and actin microfilaments as well as root growth and morphology of
      Arabidopsis thaliana seedlings. Inhibiting PLC activity using the aminosteroid
      U73122 significantly inhibited root elongation and disrupted root morphology in a
      concentration-dependent manner, with the response being saturated at 5 MUM,
      whereas the inactive analogue U73343 was ineffective. The primary root appeared
      to lose growth directionality accompanied by root waving and formation of curls.
      Immunolabelling of roots exposed to increasingly higher U73122 concentrations
      revealed that the normal transverse arrays of cortical microtubules in the
      elongation zone became progressively more disorganized or depolymerized, with the
      disorganization appearing within 1 h of incubation. Likewise, actin microfilament
      arrays also were disrupted. Inhibiting PLC using an alternative inhibitor,
      neomycin, caused similar disruptions to both cytoskeletal organization and root
      morphology. In seedlings gravistimulated by rotating the culture plates by 90
      degrees , both U73122 and neomycin disrupted the normal gravitropic growth of
      roots and etiolated hypocotyls. The effects of PLC inhibitors are therefore
      consistent with the notion that, as with phospholipases A and D, PLC likewise
      interacts with the cytoskeleton, alters growth morphology, and is involved in
      gravitropism.

PMID- 20803216
TI  - Identification and characterization of microRNAs and their target genes in
      tobacco (Nicotiana tabacum).
AB  - microRNAs (miRNAs) are a recently discovered class of small (~21 nt) endogenous
      gene regulators that have been shown to play an important role in plant growth
      and development by aiding in organ maturation, hormone signaling, tissue
      differentiation, and plant tolerance to environmental stress. Since a list of
      miRNAs has never been generated for tobacco, we employed genome survey sequence
      analysis to computationally identify 259 potentially conserved tobacco miRNAs,
      belonging to 65 families, and validated 11 of these miRNAs using qRT-PCR. The 65
      miRNA families were dramatically different in size. miRNA precursor (pre-miRNA)
      sequence analysis showed that tobacco pre-miRNAs greatly varied from 45 to 635 nt
      in length with an average of 141 +/- 108 nt. We were also able to determine the
      presence of antisense miRNAs as well as miRNA clusters in tobacco. Using
      previously established protocols, a total of 1,225 potential target genes were
      predicted for the newly identified tobacco miRNAs. These target genes include
      transcription factors, DNA replication proteins, metabolic enzymes, as well as
      other gene targets necessary for proper plant maturation. The results of this
      study show that conserved miRNAs exist in tobacco and suggest that these miRNAs
      may play an important role in tobacco growth and development.

PMID- 20803217
TI  - Construction of a high-density composite map and comparative mapping of
      segregation distortion regions in barley.
AB  - Segregation distortion can negatively impact on gains expected using selection.
      In order to increase our understanding of genetic factors that may influence the
      extent and direction of segregation distortion, segregation distortion analyses
      were conducted in four different doubled haploid (DH) populations. A high-density
      composite map of barley was then constructed by integrating information from the
      four populations. The composite map contained 2,111 unique loci, comprising RFLP,
      SSR and DArT markers and spanned 1,136 cM. In the four populations investigated,
      the proportion of markers with segregation distortion ranged from 15 to 38%,
      depending on the population. The highest distortion was observed in populations
      derived by the microspore culture technique. Distorted loci tended to be
      clustered, which allowed definition of segregation distortion regions (SDRs). A
      total of 14 SDRs were identified in the 4 populations. Using the high-density
      composite map, several SDRs were shown to have consistent map locations in two or
      more populations; one SDR on chromosome 1H was present in all four populations.
      The analysis of haplotypes underlying seven SDRs indicated that in three cases
      the under-represented haplotypes were common across populations, but for four
      SDRs the under-represented haplotypes varied across populations. Six of the seven
      centromeric regions harboured SDRs suggesting that genetic processes related to
      position near a centromere caused the segregation distortion in these SDRs. Other
      SDRs were most likely due to the methods used to produce the DH populations. The
      association of the SDRs identified in this study and some of the genes involved
      in the process of haploid production described in other studies were compared.
      The composite map constructed in this study provides an additional resource for
      the barley community via increased genome coverage and the provision of
      additional marker options. It has also enabled further insights into mechanisms
      that underpin segregation distortion.

PMID- 20803219
TI  - Increased risk of phosphorus limitation at higher temperatures for Daphnia magna.
AB  - Invertebrate herbivores frequently face growth rate constraints due to their high
      demands for phosphorus (P) and nitrogen (N). Temperature is a key modulator of
      growth rate, yet the interaction between temperature and P limitation on somatic
      growth rate is scarcely known. To investigate this interaction, we conducted a
      study on the somatic growth rate (SGR) of the cladoceran Daphnia magna, known to
      be susceptible to P-limitation. We determined the SGR across a broad range of
      dietary P content of algae (carbon (C):P ratios (125-790), and at different
      temperatures (10-25 degrees C). There was a strong impact of both temperature and
      C:P ratio on the SGR of D. magna, and also a significant interaction between both
      factors was revealed. The negative effect of dietary C:P on growth rate was
      reduced with decreased temperature. We found no evidence of P limitation at
      lowest temperature, suggesting that enzyme kinetics or other measures of food
      quality overrides the demands for P to RNA and protein synthesis at low
      temperatures. These findings also indicate an increased risk of P limitation and
      thus reduced growth efficiency at high temperatures.

PMID- 20803218
TI  - Sand and sandbar willow: a feedback loop amplifies environmental sensitivity at
      the riparian interface.
AB  - Riparian or streamside zones support dynamic ecosystems with three interacting
      components: flowing water, alluvia (river-transported sediments), and vegetation.
      River damming influences all three, and subsequent responses can provide insight
      into underlying processes. We investigated these components along the 315-km
      Hells Canyon corridor of the Snake River that included reaches upstream, along,
      and downstream from three large dams and reservoirs, and along the Salmon River,
      a free-flowing tributary. Sandbar willow was generally the woody plant at the
      lowest bank position and was abundant along upstream reaches (53, 45, 67% of
      transects), sparse along reservoirs (11, 12, 0%), and sparse along the Snake
      River downstream (11%). It was prolific along the undammed Salmon River (83%) and
      intermediate along the Snake River below the Salmon inflow (27%), indicating
      partial recovery with the contribution of water and sediments. Along these
      rivers, it commonly occurred on sandy substrates, especially on shallow-sloped
      surfaces, and emerged from interstitial sands between cobbles on steeper
      surfaces. However, along the Snake River below the dams, sandbars have eroded and
      willows were sparse on remnant, degrading sand surfaces. We conclude that a
      feedback loop exists between sands and sandbar willow. Sand favors willow
      colonization and clonal expansion, and reciprocally the extensively branched
      willows create slack-water zones that protect and trap sands. This feedback may
      sustain surface sands and sandbar willows along free-flowing river systems and it
      amplifies their mutual vulnerability to river damming. Following damming,
      sediment-depleted water is released downstream, eroding surface sands and
      reducing willow colonization and expansion. With willow decline, sands are
      further exposed and eroded, compounding these impacts. From this feedback, we
      predict the coordinated depletion of surface sands and riparian willows along
      dammed rivers throughout the Northern Hemisphere.

PMID- 20803220
TI  - Impaired food transportation in Parkinson's disease related to lingual
      bradykinesia.
AB  - This study aimed to analyze quantitatively videofluoroscopic (VF) images of
      patients with Parkinson's disease (PD), to evaluate if the predicted factors of
      the oral phase of swallowing deteriorated with PD progression, and to demonstrate
      a relationship between the abnormal movements of the tongue and food
      transportation. Thirty PD patients were recruited and divided into mild/moderate
      (Hoehn & Yahr stages II and III) and advanced (stages IV and V) groups. They
      underwent measurement of tongue strength and VF using 5 ml of barium gelatin
      jelly as a test food. We measured the speed of bolus movement and the range of
      tongue and mandible movements during oropharyngeal transit time. The maximum
      tongue pressure of the mild/moderate group was significantly larger than that of
      advanced group (p = 0.047). The oropharyngeal transit time of the mild/moderate
      group was significantly shorter than that of the advanced group (p = 0.045).
      There was a significant negative correlation between the speed of tongue movement
      and the oropharyngeal transit time (p = 0.003, R = -0.527). Prolonged mealtimes
      and the ejection of insufficiently masticated food from the oral cavity into
      oropharynx were associated with PD progression. These results indicate the
      importance of the oral phase of swallowing in PD patients.

PMID- 20803221
TI  - Phenological changes and reduced seasonal synchrony in western Poland.
AB  - Botanical gardens offer continuity for phenological recording in observers,
      protocols and plant specimens that may not be achievable from other sources.
      Here, we examine phenological change and synchrony from one such garden in
      western Poland. We analysed 66 botanical phenophases and 18 interphase intervals
      recorded between 1977 and 2007 from the Poznan Botanical Garden. These were
      examined for trends through time and responsiveness to temperature. Furthermore,
      we derived measures of synchrony for start of spring and end of autumn events to
      assess if these had changed over time. All 39 events with a mean date before mid
      July demonstrated a significant negative relationship with temperature. Where
      autumn events were significantly related to temperature, they indicated a
      positive relationship. Typically, spring events showed an advance over time and
      autumn events a delay. Interphase intervals tended to lengthen over the study
      period. The measures of synchrony changed significantly over time suggesting less
      synchrony among spring events and also among autumn events. In combination, these
      results suggest increases in growing season length. However, responses to a
      changing climate were species-specific. Thus, the transitions from winter into
      spring and from autumn into winter are becoming less clearly defined.

PMID- 20803222
TI  - Guidelines for the control of nausea and vomiting with chemotherapy of low or
      minimal emetic potential.
AB  - PURPOSE: The purpose of this study is to update the guidelines for antiemetic
      therapy to be used with anticancer agents of low to minimal emetic potential.
      METHODS: Experts from the Multinational Association of Supportive Care in Cancer
      (MASCC) met in Perugia in 2009 to revise the MASCC antiemetic consensus
      guidelines. There is an increasing number of anticancer agents which are
      classified as being associated with a low or minimal risk of nausea and vomiting.
      However, the emetic potential of such agents and particularly those given as
      prolonged oral therapy is not well documented, and neither is the optimal
      antiemetic therapy. RESULTS: The consensus is that patients receiving anticancer
      therapy of low emetic potential should receive single-agent antiemetic
      prophylaxis such as dexamethasone, 5 hydroxytryptamine3 (5HT3) receptor
      antagonists, or dopamine receptor antagonists. Those receiving anticancer therapy
      of minimal emetic potential and who have no prior history of nausea and vomiting
      should not receive antiemetic prophylaxis. Those who experience nausea and
      vomiting subsequently can receive single-agent dexamethasone, 5HT3 receptor
      antagonists, or dopamine receptor antagonists. CONCLUSIONS: More data are needed
      on the emetic potential and the outcome of antiemetic treatment with agents
      likely to fall into the low or minimal emetic potential category.

PMID- 20803223
TI  - Maximal aerobic power in patients with chronic low back pain: a comparison with
      healthy subjects.
AB  - The objective of the study was to compare the maximal aerobic capacity of
      patients with chronic low back pain with healthy asymptomatic controls matched
      for age, gender and level of physical activity at work and during sports
      activities. Reported data in the literature with respect to aerobic capacity in
      patients with chronic low back pain are not conclusive. Nevertheless, based on
      the assumption that chronic low back pain leads to deconditioning, physical
      training programs are widely used as a treatment. A total of 70 patients with
      chronic low back pain and 70 healthy asymptomatic subjects completed
      questionnaires regarding demographics and performed a graded maximal exercise
      test until exhaustion on a cycle ergometer. The maximal aerobic power was
      measured by indirect calorimetry. Heart rate, respiratory exchange ratio and
      blood lactate levels were also measured. The test was considered maximal when
      VO2max achievement criteria were obtained. VO2max values were compared among
      groups. The absolute and normalized for weight values of VO2max measured in
      patients with chronic low back pain were significantly lower than that of the
      control group. Independent comparison between men and women showed that absolute
      values of VO2max are also significantly lower in men and women with chronic low
      back pain. Women reached absolute and normalized for weight VO2max values
      significantly lower than those of men, both in chronic low back pain and control
      group. In conclusion, chronic low back pain patients, especially women, seem to
      have a reduced aerobic capacity compared to healthy asymptomatic subjects.

PMID- 20803224
TI  - Comparison of radiographic and computed tomographic measurement of pedicle and
      vertebral body dimensions in Koreans: the ratio of pedicle transverse diameter to
      vertebral body transverse diameter.
AB  - This study was designed to investigate the characteristics of pedicle transverse
      diameters (PD), vertebral body transverse diameters (VBD), especially the ratios
      of PD/VBD (CT ratio), which has never been discussed, in Koreans using computed
      tomography (CT) scans and to evaluate the possibility of obtaining more accurate
      estimations of PD from plain radiographs using the CT ratios in each spine level.
      The T1-L5 vertebrae of 50 participants were analyzed prospectively with CT scans
      (CT-VBD and CT-PD), and the T9-L5 vertebrae of the same participants were
      investigated with plain radiographs (X-VBD and X-PD). The CT ratio had a higher
      correlation with the CT-PD (r2 = 0.630) from T1 to L5, especially in the lower
      thoracic and lumbar spine (T9-L5, r2 = 0.737). The correlation of VBDs between
      the two radiologic tools (r2 = 0.896) was higher than that of the PDs (r2 =
      0.665). Based on the data, equations for the estimation of a more accurate PD
      from plain radiographs were developed as follows: estimated PD = estimated VBD *
      [1.014 * (X-VBD) + 0.152] * the mean CT ratio at each spinal level. The
      correlation between the estimated PD and the CT-PD (r2 = 0.852) was improved
      compared with that (r2 = 0.665) between the X-PD and the CT-PD. In conclusion,
      the CT ratio showed a very similar changing trends to CT-PD from T1 to L5
      regardless of sex and body mass, and the measurement error of PD from only plain
      radiographs could be minimized using estimated VBD and the mean CT ratio at each
      spinal level.

PMID- 20803225
TI  - Vitamin B12 as a carrier for targeted platinum delivery: in vitro cytotoxicity
      and mechanistic studies.
AB  - It is attractive to use vitamin B12 as a carrier for targeted delivery of
      cytotoxic agents such as platinum complexes owing to the high demand for vitamin
      B12 by fast proliferating cells. The basic {B12-CN-Pt(II)} conjugates are
      recognized by intracellular enzymes and converted to coenzyme B12 in an enzymatic
      adenosylation assay. The reductive adenosylation of {B12-CN-Pt(II)} conjugates
      leads to the release of the Pt(II) complexes; thus, {B12-CN-Pt(II)} conjugates
      can be considered as prodrugs. It is important not only to elucidate the activity
      of the cisplatin-B12 conjugates, but also to understand the mode of action on a
      molecular level. Chemical reduction of {B12-CN-Pt(II)} conjugates with
      cobaltocene yielded cob(II)alamin and induced release of the corresponding Pt(II)
      species. Kurnakov tests and coordination of 2'-deoxyguanosine or GMP to the
      released Pt(II) complexes allowed isolation and characterization of Pt(II)
      complexes as released during enzymatic adenosylation. The biological activity of
      these Pt(II) complexes was evaluated. Since the cleaved Pt(II) complexes show
      cytotoxicity, the {B12-CN-Pt(II)} conjugates can be used for specific targeting
      of cancer cells and therapeutic drug delivery. Preliminary in vitro cytotoxicity
      studies indicated lower activity (IC(50) between 8 and 88 MUM) than found for
      pure cisplatin. Since active transport and receptor-mediated uptake limits the
      intracellular {B12-CN-Pt(II)} concentration, comparison with pure cisplatin is of
      limited use. We could show that the Pt(II) complexes cleaved from B12 exerted a
      cytotoxicity comparable to that of cisplatin itself. Cytotoxicity studies in
      vitamin B12 free media showed a dependence on the addition of transcobalamin II
      for B12-Pt(II) conjugates.

PMID- 20803226
TI  - Epidemiology of Streptococcus pneumoniae and Staphylococcus aureus colonization
      in healthy Venezuelan children.
AB  - Streptococcus pneumoniae and Staphylococcus aureus cause significant morbidity
      and mortality worldwide. We investigated both the colonization and co
      colonization characteristics for these pathogens among 250 healthy children from
      2 to 5 years of age in Merida, Venezuela, in 2007. The prevalence of S.
      pneumoniae colonization, S. aureus colonization, and S. pneumoniae-S. aureus co
      colonization was 28%, 56%, and 16%, respectively. Pneumococcal serotypes 6B
      (14%), 19F (12%), 23F (12%), 15 (9%), 6A (8%), 11 (8%), 23A (6%), and 34 (6%)
      were the most prevalent. Non-respiratory atopy was a risk factor for S. aureus
      colonization (p = 0.017). Vaccine serotypes were negatively associated with
      preceding respiratory infection (p = 0.02) and with S. aureus colonization (p =
      0.03). We observed a high prevalence of pneumococcal resistance against
      trimethoprim-sulfamethoxazole (40%), erythromycin (38%), and penicillin (14%).
      Semi-quantitative measurement of pneumococcal colonization density showed that
      children with young siblings and low socioeconomic status were more densely
      colonized (p = 0.02 and p = 0.02, respectively). In contrast, trimethoprim
      sulfamethoxazole- and multidrug-resistant-pneumococci colonized children sparsely
      (p = 0.03 and p = 0.01, respectively). Our data form an important basis to
      monitor the future impact of pneumococcal vaccination on bacterial colonization,
      as well as to recommend a rationalized and restrictive antimicrobial use in our
      community.

PMID- 20803227
TI  - Crucial epitopes of Wuchereria bancrofti abundant larval transcript recognized in
      natural infection.
AB  - Lymphatic filariasis is a tropical disease, with over 40 million people seriously
      incapacitated due to lymphangitis and elephantiasis. Over 99% of infections are
      caused by the nematode Wuchereria bancrofti. Expressed sequence tag (EST)
      analysis of filarial genome identified novel infective larval (L3) stage-specific
      antigen, abundant larval transcript (ALT-2), which was shown to be highly
      essential for parasite establishment and survival in the host. The unique
      structural features and immunological characteristics of ALT-2 indicate the
      presence of critical motifs that needs to be explored in natural human infection
      for understanding and management of the disease. In order to dissect the epitopes
      of ALT protein recognized in humans, eight peptides spanning the entire protein
      sequence were selected based on in-silico epitope prediction and synthesized.
      Analysis of the reactivity of W. bancrofti ALT-2 synthetic peptides with clinical
      sera (n = 40) from endemic areas identified epitopes recognized by putatively
      immune sera, of which two comprise the highly variable acidic domain (21-60).
      Interestingly, our study also revealed crucial epitopes recognized by
      microfilaremic (MF) sera with significantly high IgG4 isotype (p < 0.001),
      implicated in immunomodulation. The epitope peptides identified were highly
      specific for MF sera and, thus, have the potential to be exploited as diagnostic
      markers.

PMID- 20803228
TI  - Trigemino-autonomic headache related to Gasperini syndrome.
AB  - We report the association of ipsilateral trigemino-autonomic headache to a case
      of right-sided nuclear facial and abducens palsy (Gasperini syndrome),
      ipsilateral hypacusis and right hemiataxia, caused by the occlusion of the right
      anterior inferior cerebellar artery. Short-lasting attacks of mild to moderate
      ipsilateral fronto-periorbital head pain, accompanied by lacrimation and mild
      conjunctival injection during more severe attacks, were present from the onset of
      symptoms, with a gradual worsening over the next few months and remitting during
      naproxen therapy. Magnetic resonance imaging showed an infarct in the right
      cerebellar peduncle, extending toward the pontine tegmentum, also involving the
      ipsilateral spinal trigeminal nucleus and tract and the trigeminal entry zone.
      Gasperini syndrome may be accompanied by ipsilateral trigemino-autonomic head
      pain.

PMID- 20803229
TI  - Vardenafil, an inhibitor of phosphodiesterase-5, blocks advanced glycation end
      product (AGE)-induced up-regulation of monocyte chemoattractant protein-1 mRNA
      levels in endothelial cells by suppressing AGE receptor (RAGE) expression via
      elevation of cGMP.
AB  - Decreased production and/or impaired action of nitric oxide (NO) play a role in
      the pathogenesis of atherosclerotic cardiovascular disease and erectile
      dysfunction (ED) in diabetic patients. Under hyperglycemic conditions, formation
      and accumulation of advanced glycation end products (AGE) have been known to
      progress, thus contributing to tissue damage in diabetes. However, effects of
      inhibitors of phosphodiesterase-5 (PDE-5), an enzyme that catalyzes the
      degradation of cyclic guanosin-monophosphate (cGMP) and subsequently blocks the
      actions of NO, on AGE-exposed endothelial cells remain unknown. Therefore, this
      study investigated whether and how vardenafil, an inhibitor of PDE-5, could block
      the deleterious effects of AGE on human umbilical vein endothelial cells (HUVEC).
      Gene and protein expression was analyzed in quantitative real-time reverse
      transcription polymerase chain reaction (RT-PCR) and western blots, respectively.
      Intracellular formation of reactive oxygen species (ROS) was evaluated with
      dihydroethidium staining. AGE increased receptor for AGE (RAGE) mRNA and protein
      levels in HUVEC, both of which were significantly inhibited by the treatments
      with 30 nM vardenafil or 5 MUM 8-Br-cGMP, an analogue of cGMP. Further,
      vardenafil reduced the AGE-induced ROS generation and subsequently inhibited up
      regulation of monocyte chemoattractant protein-1 (MCP-1) mRNA levels in HUVEC. We
      demonstrated here for the first time that vardenafil could block the AGE-induced
      up-regulation of MCP-1 mRNA levels in HUVEC by suppressing RAGE expression and
      subsequent ROS generation via elevation of cGMP. Our present results suggest that
      vardenafil directly acts on endothelial cells and it could work as an anti
      inflammatory agent against AGE.

PMID- 20803230
TI  - Spotlight on post-transcriptional control in the circadian system.
AB  - An endogenous timing mechanism, the circadian clock, causes rhythmic expression
      of a considerable fraction of the genome of most organisms to optimally align
      physiology and behavior with their environment. Circadian clocks are self
      sustained oscillators primarily based on transcriptional feedback loops and post
      translational modification of clock proteins. It is increasingly becoming clear
      that regulation at the RNA level strongly impacts the cellular circadian
      transcriptome and proteome as well as the oscillator mechanism itself. This
      review focuses on posttranscriptional events, discussing RNA-binding proteins
      that, by influencing the timing of pre-mRNA splicing, polyadenylation and RNA
      decay, shape rhythmic expression profiles. Furthermore, recent findings on the
      contribution of microRNAs to orchestrating circadian rhythms are summarized.

PMID- 20803231
TI  - The multi-targeted kinase inhibitor sorafenib inhibits human cytomegalovirus
      replication.
AB  - Human cytomegalovirus (HCMV) is a major pathogen in immunocompromised
      individuals. Here, non-toxic concentrations of the anti-cancer kinase inhibitor
      sorafenib were shown to inhibit replication of different HCMV strains (including
      a ganciclovir-resistant strain) in different cell types. In contrast to
      established anti-HCMV drugs, sorafenib inhibited HCMV major immediate early
      promoter activity and HCMV immediate early antigen (IEA) expression. Sorafenib is
      known to inhibit Raf. Comparison of sorafenib with the MEK inhibitor U0126
      suggested that sorafenib inhibits HCMV IEA expression through inhibition of Raf
      but independently of signaling through the Raf downstream kinase MEK 1/2. In
      concordance, siRNA-mediated depletion of Raf but not of MEK-reduced IEA
      expression. In conclusion, sorafenib diminished HCMV replication in clinically
      relevant concentrations and inhibited HCMV IEA expression, a pathophysiologically
      relevant event that is not affected by established anti-HCMV drugs. Moreover, we
      demonstrated for the first time that Raf activation is involved in HCMV IEA
      expression.

PMID- 20803233
TI  - High resolution 13C-detected solid-state NMR spectroscopy of a deuterated
      protein.
AB  - High resolution 13C-detected solid-state NMR spectra of the deuterated beta-1
      immunoglobulin binding domain of the protein G (GB1) have been collected to show
      that all 15N, 13C', C13Calpha and 13Cbeta sites are resolved in C13C-13C and 15N
      C13C spectra, with significant improvement in T(2) relaxation times and
      resolution at high magnetic field (750 MHz). The comparison of echo T(2) values
      between deuterated and protonated GB1 at various spinning rates and under
      different decoupling schemes indicates that 13Calpha T(2)' times increase by
      almost a factor of two upon deuteration at all spinning rates and under moderate
      decoupling strength, and thus the deuteration enables application of scalar-based
      correlation experiments that are challenging from the standpoint of transverse
      relaxation, with moderate proton decoupling. Additionally, deuteration in large
      proteins is a useful strategy to selectively detect polar residues that are often
      important for protein function and protein-protein interactions.

PMID- 20803234
TI  - Dietary zinc mediates inflammation and protects against wasting and metabolic
      derangement caused by sustained cigarette smoke exposure in mice.
AB  - In mouse asthma models, inflammation can be modulated by zinc (Zn). Given that
      appetite loss, muscle wasting and poor nutrition are features of chronic
      obstructive pulmonary disease (COPD) and that poor dietary Zn intake is in itself
      accompanied by growth retardation and appetite loss, we hypothesised that dietary
      Zn limitation would not only worsen airway inflammation but also exaggerate
      metabolic effects of cigarette smoke (CS) exposure in mice. Conversely, Zn
      supplementation would lessen inflammation. Mice were exposed to CS [2* 2RF,
      3*/day; 15 min/cigarette] and fed diets containing 2, 20 or 140 mg/kg Zn ad
      libitum. Airway cells were collected by bronchoalveolar lavage (BAL). Plasma Zn
      was measured by fluorometric assay. Inflammatory, metabolic and Zn transport
      markers were measured by real-time RT-PCR. Mice fed low Zn diets had less plasma
      labile zinc (0-0.18 MUM) than mice fed moderate (0.61-0.98 MUM) or high (0.77-1.1
      MUM) Zn diets (SDs 0.1-0.4, n = 8-10). Smoke exposure increased plasma and BAL
      labile Zn (1.5-2.5 fold, P < 0.001), bronchoalveolar macrophages (2.0 fold, P <
      0.0001) and MT-1 (1.5 fold), MIP-2 (2.3 fold) and MMP-12 (3.5 fold) mRNA. Zn
      supplementation reduced alveolar macrophage numbers by 62 and 52% in sham and
      smoke-exposed mice, respectively (Zn effect: P = 0.011). Gastrocnemius, soleus
      and tibialis anterior muscle mass were affected by both smoke and dietary Zn in
      the order of 3-7%. The 50-60% reduction in alveolar macrophages in Zn
      supplemented mice supports our evolving hypothesis that Zn is an important anti
      inflammatory mediator of airway inflammation. Restoring airway Zn levels through
      dietary supplementation may lessen the severity of lung inflammation when Zn
      intake is low.

PMID- 20803235
TI  - Biodepollution of wastewater containing phenolic compounds from leather industry
      by plant peroxidases.
AB  - This study deals with the use of peroxidases (POXs) from Allium sativum, Ipomoea
      batatas, Raphanus sativus and Sorghum bicolor to catalyze the degradation of free
      phenolic compounds as well as phenolic compounds contained in wastewater from
      leather industry. Secretory plant POXs were able to catalyze the oxidation of
      gallic acid, ferulic acid, 4-hydroxybenzoic acid, pyrogallol and 1,4-tyrosol
      prepared in ethanol 2% (v:v). Efficiency of peroxidase catalysis depends strongly
      on the chemical nature of phenolic substrates and on the botanical source of the
      enzymes. It appeared that POX from Raphanus sativus had the highest efficiency.
      Results show that POXs can also remove phenolic compounds present in industrial
      wastewater such as leather industry. Removal of phenolic compounds in wastewater
      from leather industry by POX was significantly enhanced by polyethylene glycol.

PMID- 20803232
TI  - The ING family tumor suppressors: from structure to function.
AB  - The Inhibitor of Growth (ING) proteins belong to a well-conserved family which
      presents in diverse organisms with several structural and functional domains for
      each protein. The ING family members are found in association with many cellular
      processes. Thus, the ING family proteins are involved in regulation of gene
      transcription, DNA repair, tumorigenesis, apoptosis, cellular senescence and cell
      cycle arrest. The ING proteins have multiple domains that are potentially capable
      of binding to many partners. It is conceivable, therefore, that such proteins
      could function similarly within protein complexes. In this case, within this
      family, each function could be attributed to a specific domain. However, the role
      of ING domains is not definitively clear. In this review, we summarize recent
      advances in structure-function relationships in ING proteins. For each domain, we
      describe the known biological functions and the approaches utilized to identify
      the functions associated with ING proteins.

PMID- 20803236
TI  - Isolation and screening of potential actinobacteria for rapid composting of rice
      straw.
AB  - Rice straw is produced as a by-product from rice cultivation, which is composed
      largely of lignocellulosic materials amenable to general biodegradation.
      Lignocellulolytic actinobacteria can be used as a potential agent for rapid
      composting of bulky rice straw. Twenty-five actinobacteria isolates were isolated
      from various in situ and in vitro rice straw compost sources. Isolates A2, A4,
      A7, A9 and A24 were selected through enzymatic degradation of starch, cellulose
      and lignin followed by the screening for their adaptability on rice straw powder
      amended media. The best adapted isolate (A7) was identified as Micromonospora
      carbonacea. It was able to degrade cellulose, hemicelluloses and carbon
      significantly (P <= 0.05) over the control. C/N ratio was reduced to 18.1 from an
      initial value of 29.3 in 6 weeks of composting thus having the potential to be
      used in large scale composting of rice straw.

PMID- 20803237
TI  - Cell surface sialic acid inhibits Cx43 gap junction functions in constructed Hela
      cancer cells involving in sialylated N-cadherin.
AB  - Numerous studies have shown that changes in the glycan structures of cells
      correlate with tumorigenesis, however, a casual link between the altered glycan
      structures and the abnormal GJIC in cancer cells is rarely studied. In this
      paper, we investigated the effects of sialic acid on the Cx43 gap junction
      functions, and clarified its potential mechanisms thereby. Sialidase
      significantly increased Cx43 gap junction functions in constructed Cx43-Hela
      cells along with down-regulation of cell surface sialic acid, which is
      dramatically reversed by sialidase inhibitor NeuAc2en. Further study indicated
      that sialidase failed to affect Cx43 at either protein or phosphorylation level,
      instead, it induced a considerable fraction of Triton X-100 insoluble, as
      compared with the untreated cells. We also found that sialidase treatment reduced
      the N-cadherin glycosylation and enhanced both Cx43-ZO-1 interaction and N
      cadherin-ZO-1 association. Moreover, sialidase promoted the cell-cell adhesion
      with elevating N-cadherin binding to beta-catenin, accompanied by increasing
      colocalization of Cx43 with microtubules at the cell periphery. Based on live
      cell microscopy, with the FARP technology in the Cx43-EGFP-Hela cells, we found
      that Cx43 in the plague recovered more quickly in sialidase treatment group,
      indicating that sialidase could promote the Cx43 traffic to the plague. Overall,
      these studies indicate cell surface sialic acid on cancer cells may suppress Cx43
      gap junction functions via inhibiting Cx43 traffic to the plague involving in
      sialylated N-cadherin, a process that likely underlies the intimate association
      between abnormal GJIC and glycosylation on cancer development.

PMID- 20803238
TI  - Scaffold percolative efficiency: in vitro evaluation of the structural criterion
      for electrospun mats.
AB  - Fibrous scaffolds of engineered structures can be chosen as promising porous
      environments when an approved criterion validates their applicability for a
      specific medical purpose. For such biomaterials, this paper sought to investigate
      various structural characteristics in order to determine whether they are
      appropriate descriptors. A number of poly(3-hydroxybutyrate) scaffolds were
      electrospun; each of which possessed a distinguished architecture when their
      material and processing conditions were altered. Subsequent culture of mouse
      fibroblast cells (L929) was carried out to evaluate the cells viability on each
      scaffold after their attachment for 24 h and proliferation for 48 and 72 h. The
      scaffolds' porosity, pores number, pores size and distribution were quantified
      and none could establish a relationship with the viability results. Virtual
      reconstruction of the mats introduced an authentic criterion, "Scaffold
      Percolative Efficiency" (SPE), with which the above descriptors were addressed
      collectively. It was hypothesized to be able to quantify the efficacy of fibrous
      scaffolds by considering the integration of porosity and interconnectivity of the
      pores. There was a correlation of 80% as a good agreement between the SPE values
      and the spectrophotometer absorbance of viable cells; a viability of more than
      350% in comparison to that of the controls.

PMID- 20803240
TI  - Development of 95-gene classifier as a powerful predictor of recurrences in node
      negative and ER-positive breast cancer patients.
AB  - Our aim was to develop an accurate diagnostic system using gene expression
      analysis by means of DNA microarray for prognosis of node-negative and estrogen
      receptor (ER)-positive breast cancer patients in order to identify a subset of
      patients who can be safely spared adjuvant chemotherapy. A diagnostic system
      comprising a 95-gene classifier was developed for predicting the prognosis of
      node-negative and ER-positive breast cancer patients by using already published
      DNA microarray (gene expression) data (n = 549) as the training set and the DNA
      microarray data (n = 105) obtained at our institute as the validation set.
      Performance of the 95-gene classifier was compared with that of conventional
      prognostic factors as well as of the genomic grade index (GGI) based on the
      expression of 70 genes. With the 95-gene classifier we could classify the 105
      patients in the validation set into a high-risk (n = 44) and a low-risk (n = 61)
      group with 10-year recurrence-free survival rates of 93 and 53%, respectively (P
      = 8.6e-7). Multivariate analysis demonstrated that the 95-gene classifier was the
      most important and significant predictor of recurrence (P = 9.6e-4) independently
      of tumor size, histological grade, progesterone receptor, HER2, Ki67, or GGI. The
      95-gene classifier developed by us can predict the prognosis of node-negative and
      ER-positive breast cancer patients with high accuracy. The 95-gene classifier
      seems to perform better than the GGI. As many as 58% of the patients classified
      into the low-risk group with this classifier could be safely spared adjuvant
      chemotherapy.

PMID- 20803239
TI  - The small molecule specific EphB4 kinase inhibitor NVP-BHG712 inhibits VEGF
      driven angiogenesis.
AB  - EphB4 and its cognitive ligand ephrinB2 play an important role in embryonic
      vessel development and vascular remodeling. In addition, several reports suggest
      that this receptor ligand pair is also involved in pathologic vessel formation in
      adults including tumor angiogenesis. Eph/ephrin signaling is a complex phenomena
      characterized by receptor forward signaling through the tyrosine kinase of the
      receptor and ephrin reverse signaling through various protein-protein interaction
      domains and phosphorylation motifs of the ephrin ligands. Therefore, interfering
      with EphR/ephrin signaling by the means of targeted gene ablation, soluble
      receptors, dominant negative mutants or antisense molecules often does not allow
      to discriminate between inhibition of Eph/ephrin forward and reverse signaling.
      We developed a specific small molecular weight kinase inhibitor of the EphB4
      kinase, NVP-BHG712, which inhibits EphB4 kinase activity in the low nanomolar
      range in cellular assays showed high selectivity for targeting the EphB4 kinase
      when profiled against other kinases in biochemical as well as in cell based
      assays. Furthermore, NVP-BHG712 shows excellent pharmacokinetic properties and
      potently inhibits EphB4 autophosphorylation in tissues after oral administration.
      In vivo, NVP-BHG712 inhibits VEGF driven vessel formation, while it has only
      little effects on VEGF receptor (VEGFR) activity in vitro or in cellular assays.
      The data shown here suggest a close cross talk between the VEGFR and EphR
      signaling during vessel formation. In addition to its established function in
      vascular remodeling and endothelial arterio-venous differentiation, EphB4 forward
      signaling appears to be an important mediator of VEGF induced angiogenesis since
      inhibition of EphB4 forward signaling is sufficient to inhibit VEGF induced
      angiogenesis.

PMID- 20803241
TI  - Additional findings at preoperative MRI: a simple golden rule for a complex
      problem?

PMID- 20803242
TI  - Production of thermotolerant entomopathogenic fungal conidia on millet grain.
AB  - Thermotolerance of entomopathogenic (insect-killing) fungi should be seriously
      considered before industrialization. This work describes the feasibility of
      millet grain as a substrate for production of thermotolerant Beauveria bassiana
      (Bb) GHA and ERL1170 and Metarhizium anisopliae (Ma) ERL1171 and ERL1540 conidia.
      First, conidial suspensions of the Bb isolates, produced on millet grain in
      polyethylene bags, were exposed to five temperatures (43-47  degrees C) at 15-min
      intervals for up to 120 min (experiment I). Agar-based quarter-strength (1/4)
      Sabouraud dextrose agar supplemented with yeast extract (SDAY) and whey permeate
      media served as controls. Millet-grain-based culture was superior in producing
      the most thermotolerant Bb conidia, followed by whey permeate agar and 1/4SDAY
      based cultures. Secondly, to compare the thermotolerance of conidia produced at
      the same conditions, the Bb isolates were then produced on agar-based millet
      powder medium, with 1/4SDAY and whey permeate agar media as controls, and the two
      Ma isolates were added (experiment II). They were then exposed to the same
      temperatures as above. More thermotolerant Bb and Ma conidia were produced on
      millet powder agar than on whey permeate agar and 1/4SDAY overall. These results
      suggest that millet grain can be used as a substrate to produce thermotolerant
      conidia in a mass production system.

PMID- 20803243
TI  - Hot-water pretreatment of cattails for extraction of cellulose.
AB  - To date in the US, production of renewable fuels, particularly ethanol, is
      primarily from food crops that are high in sugar and starch. The use of arable
      land for fuel rather than food production and the use of a food source for fuel
      rather than food have created issues in pricing and availability of traditional
      foods and feed. The use of cattails to produce biofuel will add value to land and
      also reduce emissions of greenhouse gases by replacing petroleum products. In
      order to investigate the feasibility of converting cattails into cellulosic
      ethanol, a hot-water pretreatment process was studied using a Dionex accelerated
      solvent extractor (ASE) varying treatment temperature and time. The pretreatment
      at 190 degrees C for more than 10 min could effectively dissolve the xylan
      fraction of cattails as soluble oligomers. Both the glucose yield and xylose
      yield obtained from the pretreated cattails increased with the escalation of the
      final pretreatment temperature, treatment time or enzyme loading. When cattails
      were pretreated at 190 degrees C for 15 min, the highest glucose yield of 77.6%
      from the cellulose was achieved in 48 h using a cellulase loading of 60 FPU/g
      glucan. The yeast Saccharomyces cerevisiae (ATCC 24858) was able to ferment
      glucose released by cattail cellulose, resulting in approximately 88.7 +/- 2.8%
      of the theoretical ethanol yield. The higher enzyme loading of 60 FPU/g glucan
      will significantly increase costs. It is recommended that further studies be
      carried out using cattails as a feedstock for bio-fuels, especially to optimize
      the economics of biological conversion processes for cattails with regard to
      reducing enzyme usage, energy input, glucose yield and xylose yield.

PMID- 20803244
TI  - Production of cellulases and xylanases under catabolic repression conditions from
      mutant PR-22 of Cellulomonas flavigena.
AB  - Derepressed mutant PR-22 was obtained by N-methyl-N'-nitro-N-nitrosoguanidine
      (MNNG) mutagenic treatment of Cellulomonas flavigena PN-120. This mutant improved
      its xylanolytic activity from 26.9 to 40 U mg(-1) and cellulolytic activity from
      1.9 to 4 U mg(-1); this represented rates almost 2 and 1.5 times higher,
      respectively, compared to its parent strain growing in sugarcane bagasse. Either
      glucose or cellobiose was added to cultures of C. flavigena PN-120 and mutant PR
      22 induced with sugarcane bagasse in batch culture. The inhibitory effect of
      glucose on xylanase activity was more noticeable for parent strain PN-120 than
      for mutant PR-22. When 20 mM glucose was added, the xylanolytic activity
      decreased 41% compared to the culture grown without glucose in mutant PR-22,
      whereas in the PN-120 strain the xylanolytic activity decreased by 49% at the
      same conditions compared to its own control. Addition of 10 and 15 mM of glucose
      did not adversely affect CMCase activity in PR-22, but glucose at 20 mM inhibited
      the enzymatic activity by 28%. The CMCase activity of the PN-120 strain was more
      sensitive to glucose than PR-22, with a reduction of CMCase activity in the range
      of 20-32%. Cellobiose had a more significant effect on xylanase and CMCase
      activities than glucose did in the mutant PR-22 and parent strain. Nevertheless,
      the activities under both conditions were always higher in the mutant PR-22 than
      in the PN-120 strain. Enzymatic saccharification experiments showed that it is
      possible to accumulate up to 10 g l(-1) of total soluble sugars from pretreated
      sugarcane bagasse with the concentrated enzymatic crude extract from mutant PR
      22.

PMID- 20803245
TI  - DTAF: an efficient probe to study cyanobacterial-plant interaction using confocal
      laser scanning microscopy (CLSM).
AB  - A variety of microscopic techniques have been utilized to study cyanobacterial
      associations with plant roots, but confocal laser scanning microscopy (CLSM) is
      the least used due to the unavailability of a suitable fluorescent dye. Commonly
      used lectins have problems with their binding ability with root cells and their
      visualization under CLSM. DTAF (5-(4,6-dichlorotriazinyl) aminofluorescein) is a
      fluorescent dye that has been widely used for staining various biological samples
      for fluorescent microscopy. It reacts with polysaccharides and peptides at
      ordinary conditions. The possible application and efficiency of DTAF for CLSM
      studies were examined in various aspects of cyanobacterial-plant interactions.
      Seedlings of Pisum sativum, Vigna rediata and Triticum aestivum were co
      cultivated and stained with DTAF as a fluorochrome. Extracellular and
      intracellular interactions of cyanobacteria and the plant root surface were
      observed by CLSM. Results were compared with staining by other commonly used
      lectins. Advantages of the use of DTAF over other stains are its penetration into
      root tissues and binding with polysaccharides, mainly the cellulose. The staining
      was smooth, which clearly showed minute details on the cell of surface and root
      hairs with higher resolution. The emission wavelength for DTAF is 517 nm, which
      is highly advantageous as cyanobacteria have auto-fluorescence at 665 nm, and
      both can be simultaneously used in CLSM by visualizing in different channels.
      This worked efficiently with all three plants used and with filamentous and
      unicellular cyanobacterial strains. Cyanobacterial presence was not only clearly
      observed on the root surface, but also inside the root tissue and epidermal
      cells. The easy protocol and absence of tissue processing make DTAF a useful
      probe for studies of cyanobacterial associations with plant roots by CLSM.

PMID- 20803246
TI  - Modeling and optimization of lipase-catalyzed production of succinic acid ester
      using central composite design analysis.
AB  - Esterification of succinic acid with oleyl alcohol catalyzed by immobilized
      Candida antarctica lipase B (Novozym 435) was investigated in this study.
      Response surface methodology (RSM) based on a five-level, four-variable central
      composite design (CCD) was used to model and analyze the reaction. A total of 21
      experiments representing different combinations of the four parameters including
      temperature (35-65 degrees C), time (30-450 min), enzyme amount (20-400 mg), and
      alcohol:acid molar ratio (1:1-8:1) were generated. A partial cubic equation could
      accurately model the response surface with a R(2) of 0.9853. The effect and
      interactions of the variables on the ester synthesis were also studied.
      Temperature was found to be the most significant parameter that influenced the
      succinate ester synthesis. At the optimal conditions of 41.1 degrees C, 272.8
      min, 20 mg enzyme amount and 7.8:1 alcohol:acid molar ratio, the esterification
      percentage was 85.0%. The model can present a rapid means for estimating the
      conversion yield of succinate ester within the selected ranges.

PMID- 20803247
TI  - Composition of sugar cane, energy cane, and sweet sorghum suitable for ethanol
      production at Louisiana sugar mills.
AB  - A challenge facing the biofuel industry is to develop an economically viable and
      sustainable biorefinery. The existing potential biorefineries in Louisiana, raw
      sugar mills, operate only 3 months of the year. For year-round operation, they
      must adopt other feedstocks, besides sugar cane, as supplemental feedstocks.
      Energy cane and sweet sorghum have different harvest times, but can be processed
      for bio-ethanol using the same equipment. Juice of energy cane contains 9.8%
      fermentable sugars and that of sweet sorghum, 11.8%. Chemical composition of
      sugar cane bagasse was determined to be 42% cellulose, 25% hemicellulose, and 20%
      lignin, and that of energy cane was 43% cellulose, 24% hemicellulose, and 22%
      lignin. Sweet sorghum was 45% cellulose, 27% hemicellulose, and 21% lignin.
      Theoretical ethanol yields would be 3,609 kg per ha from sugar cane, 12,938 kg
      per ha from energy cane, and 5,804 kg per ha from sweet sorghum.

PMID- 20803248
TI  - Activation of GH signaling and GH-independent stimulation of growth in zebrafish
      by introduction of a constitutively activated GHR construct.
AB  - Growth hormone (GH) gene transfer can markedly increase growth in transgenic
      fish. In the present study we have developed a transcriptional assay to evaluate
      GH-signal activation (GHSA) in zebrafish embryos. By analyzing the transcription
      of c-fos and igf1, and the promoter activity of spi2.1, in zebrafish embryos
      injected with different constructs, we found that overexpression of either GH or
      growth hormone receptor (GHR) resulted in GHSA, while a synergetic overexpression
      of GH and GHR gave greater activation. Conversely, overexpression of a C-terminal
      truncated dominant-negative GHR (DeltaC-GHR) efficiently blocked GHSA epistatic
      to GH overexpression, demonstrating the requirement for a full GHR homodimer in
      signaling. In view of the importance of signal-competent GHR dimerization by
      extracellular GH, we introduced into zebrafish embryos a constitutively activated
      GHR (CA-GHR) construct, which protein products constitutively dimerize the GHR
      productively by Jun-zippers to activate downstream signaling in vitro.
      Importantly, overexpression of CA-GHR led to markedly higher level of GHSA than
      the synergetic overexpression of GH and GHR. CA-GHR transgenic zebrafish were
      then studied in a growth trial. The transgenic zebrafish showed higher growth
      rate than the control fish, which was not achievable by GH transgenesis in these
      zebrafish. Our study demonstrates GH-independent growth by CA-GHR in vivo which
      bypasses normal IGF-1 feedback control of GH secretion. This provides a novel
      means of producing growth enhanced transgenic animals based on molecular protein
      design.

PMID- 20803250
TI  - Analysis of the microbial community and geochemistry of a sediment core from
      Great Slave Lake, Canada.
AB  - Sediment cores taken from Great Slave Lake, Canada, were analysed to investigate
      their metabolically active microbial populations and geochemistry. The
      amplification of cDNA detected metabolically active bacterial (50 separate bands)
      and archaeal (49 separate band) communities. The bacterial communities were
      further resolved indicating active actinobacterial and gamma-proteobacterial
      communities (36 and 43 individual bands respectively). Redundancy discriminate
      analysis and Monte Carlo permutation testing demonstrated the significant impact
      of geochemical parameters on microbial community structures. Geochemical analyses
      suggest that the upper 0.4 m represents soil weathering and erosion in the lake
      catchment. An increase in organic carbon in the lower core suggests either more
      primary productivity, indicating warmer climate conditions, associated with
      Holocene Climatic Optimum conditions pre 5,000 years BP or change from a reducing
      environment in the lower core to an oxidizing environment during more recent
      deposition. Drivers for bacterial, archaeal and actinobacterial community
      structures were sediment particle size, and its mineral composition. Depth also
      significantly affected gamma- proteobacterial community structure. In contrast
      the organic carbon content did not significantly shape the microbial community
      structures within the sediment. This study indicates that geochemical parameters
      significantly contribute to microbial community structure in these sediments.

PMID- 20803249
TI  - Pig transgenesis by Sleeping Beauty DNA transposition.
AB  - Modelling of human disease in genetically engineered pigs provides unique
      possibilities in biomedical research and in studies of disease intervention.
      Establishment of methodologies that allow efficient gene insertion by non-viral
      gene carriers is an important step towards development of new disease models. In
      this report, we present transgenic pigs created by Sleeping Beauty DNA
      transposition in primary porcine fibroblasts in combination with somatic cell
      nuclear transfer by handmade cloning. Gottingen minipigs expressing green
      fluorescent protein are produced by transgenesis with DNA transposon vectors
      carrying the transgene driven by the human ubiquitin C promoter. These animals
      carry multiple copies (from 8 to 13) of the transgene and show systemic transgene
      expression. Transgene-expressing pigs carry both transposase-catalyzed insertions
      and at least one copy of randomly inserted plasmid DNA. Our findings illustrate
      critical issues related to DNA transposon-directed transgenesis, including
      coincidental plasmid insertion and relatively low Sleeping Beauty transposition
      activity in porcine fibroblasts, but also provide a platform for future
      development of porcine disease models using the Sleeping Beauty gene insertion
      technology.

PMID- 20803251
TI  - Bacterial communities reflect the spatial variation in pollutant levels in
      Brazilian mangrove sediment.
AB  - The majority of oil from oceanic oil spills converges on coastal ecosystems such
      as mangrove forests. A major challenge to mangrove bioremediation is defining the
      mangrove's pollution levels and measuring its recuperation from pollution.
      Bioindicators can provide a welcome tool for defining such recovery. To determine
      if the microbial profiles reflected variation in the pollutants, samples from
      different locations within a single mangrove with a history of exposure to oil
      were chemically characterised, and the microbial populations were evaluated by a
      comprehensive range of conventional and molecular methods. Multivariate
      ordination of denaturing gradient gel electrophoresis (DGGE) microbial community
      fingerprints revealed a pronounced separation between the sediment and
      rhizosphere samples for all analysed bacterial communities (Bacteria,
      Betaproteobacteria, Alphaproteobacteria, Actinobacteria and Pseudomonas). A
      Mantel test revealed significant relationships between the sediment chemical
      fertility and oil-derived pollutants, most of the bacterial community
      fingerprints from sediment samples, and the counts by different cultivation
      strategies. The level of total petroleum hydrocarbons was significantly
      associated with the Bacteria and Betaproteobacteria fingerprints, whereas
      anthracene and the total level of polycyclic aromatic hydrocarbons were
      associated with the Actinobacteria. These results show that microbial communities
      from the studied mangrove reflect the spatial variation of the chemicals in the
      sediment, demonstrating the specific influences of oil-derived pollutants.

PMID- 20803252
TI  - Pichia anomala in grain biopreservation.
AB  - Cereal grain is a major component of food and feed in large parts of the world.
      The microbial flora on cereal grains may interfere with hygiene and storage
      stability, palatability and bioavailability of minerals and proteins may depend
      on the composition of the microbial population. Therefore, it is of primary
      interest to control the microbial species present on cereal grain. Inoculation of
      the biocontrol yeast Pichia anomala to cereal feed grain improved feed hygiene by
      reduction of moulds and Enterobacteriaceae, and enhanced the nutritional value by
      increasing the protein content and reducing the concentration of the
      antinutritional compound phytate. P. anomala strains showed a high phytase
      activity, for some strains also considerable extracellular phytase activity was
      observed. A certain maximum in biomass concentration was never exceeded
      indicating cell density induced growth inhibition of P. anomala.

PMID- 20803253
TI  - Food insecurity among Latin American recent immigrants in Toronto.
AB  - Food security is an important social determinant of health. The 2004 Canadian
      Community Health Survey, Cycle 2.2 reported high prevalence of food insecurity
      among low income households and those formed by recent immigrants. Exploration of
      the extent and correlates of food insecurity among recent Latin Americans (LA)
      immigrants is essential considering they encompasses an increasing number of
      young immigrants, many of whom, despite relatively high education, are unemployed
      or have low wage positions. This study examines the extent of food insecurity and
      its correlates among recent Latin American (LA) immigrants in Toronto. A cross
      sectional study was conducted with a convenience sample of 70 adult LA recent
      immigrants. Participants were recruited from selected community health centres
      across Toronto using snow ball sampling. Data were collected using questionnaires
      in face-to-face interviews with primary household care givers. A considerably
      high rate of food insecurity (56%) was found among participants. Household food
      insecurity was highly related to: being on social assistance; limited proficiency
      in English; and the use of foodbanks. Our findings indicate that the primary
      correlate of a household's food security status is income, which suggests the
      potential for strategies to improve the financial power of new immigrants to
      purchase sufficient, nutritious, and culturally acceptable food. Enhancing the
      employability of new immigrants, reforming the income structure for working
      adults beyond social assistance, and providing more subsidized English language
      and housing programs may be effective.

PMID- 20803254
TI  - Challenges in identifying Native Hawaiians and Pacific Islanders in population
      based cancer registries in the U.S.
AB  - Lack of disaggregated data for Native Hawaiians and Pacific Islanders (NHPIs) in
      the U.S. has resulted in severe gaps in understanding health disparities and
      unique health needs of NHPIs. Telephone interviews were conducted with 272 cancer
      patients identified by a population-based cancer registry. The self-reported
      NHPIs status was compared with that identified by the registry. Sensitivity,
      Specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV)
      were calculated. Alternative NHPIs identification methods were explored. The
      registry had acceptable sensitivity (89%), specificity (96%) and NPV (99%), but
      low PPV (62%) in identifying NHPIs. Using additional information on surname and
      birthplace from the registry improved the identification of NHPIs, but either
      increased the false positive or decreased the counts of true NHPIs cases.
      Improved data collection methods and practices in identifying NHPIs in population
      based cancer registries are needed and caution in interpreting cancer data for
      NHPIs is warranted.

PMID- 20803255
TI  - Antifungal activity of antifungal drugs, as well as drug combinations against
      Exophiala dermatitidis.
AB  - To evaluate the in vitro efficacy of common antifungal drugs, as well as the
      interactions of caspofungin with voriconazole, amphotericin B, or itraconazole
      against the pathogenic black yeast Exophiala dermatitidis from China, the minimal
      inhibitory concentrations (MICs) of terbinafine, voriconazole, itraconazole,
      amphotericin B, fluconazole, and caspofungin against 16 strains of E.
      dermatitidis were determined by using CLSI broth microdilution method (M38-A2).
      The minimal fungicidal concentrations (MFCs) were also determined. Additionally,
      the interactions of caspofungin with voriconazole, amphotericin B, itraconazole
      or fluconazole, that of terbinafine with itraconazole, or that of fluconazole
      with amphotericin B were assessed by using the checkerboard technique. The
      fractional inhibitory concentration index (FICI) was used to categorize drug
      interactions as following, synergy, FICI <= 0.5; indifference, FICI > 0.5 and
      <=4.0; or antagonism, FICI > 4.0. The MIC ranges of terbinafine, voriconazole,
      itraconazole, amphotericin B, fluconazole, and caspofungin against E.
      dermatitidis were 0.06-0.125 mg/l, 0.25-1.0 mg/l, 1.0-2.0 mg/l, 1.0-2.0 mg/l, 16
      64 mg/l, and 32-64 mg/l, respectively. The in vitro interactions of caspofungin
      with voriconazole, amphotericin B, and itraconazole showed synergic effect
      against 10/16(62.5%), 15/16(93.75%), and 16/16(100%) isolates, while that of
      caspofungin with fluconazole showed indifference. Besides, the interaction of
      terbinafine with itraconazole as well as that of fluconazole with amphotericin B
      showed indifference. Terbinafine, voriconazole, itraconazole, and amphotericin B
      have good activity against E. dermatitidis. The combinations of caspofungin with
      voriconazole, amphotericin B or itraconazole present synergic activity against E.
      dermatitidis. These results provide the basis for novel options in treating
      various E. dermatitidis infections.

PMID- 20803257
TI  - Professional values in community and public health pharmacy.
AB  - General practice (community) pharmacy as a healthcare profession is largely
      devoted to therapeutic treatment of individual patients whether in dispensing
      medically authorised prescriptions or by providing members of the public with
      over-the-counter advice and service for a variety of common ailments. Recently,
      community pharmacy has been identified as an untapped resource available to
      undertake important aspects of public health and in particular health promotion.
      In contrast to therapeutic treatment, public health primarily concerns the health
      of the entire population, rather than the health of individuals (Childress et al.
      in J Law Med Ethics 30:170-178, 2002). Thus, an important question for the
      profession is whether those moral and professional values that are appropriate to
      the therapeutic care of individual patients are relevant and adequate to support
      the additional public health role.

PMID- 20803256
TI  - Chemosensitization of aflatoxigenic fungi to antimycin A and strobilurin using
      salicylaldehyde, a volatile natural compound targeting cellular antioxidation
      system.
AB  - Various species of fungi in the genus Aspergillus are the most common causative
      agents of invasive aspergillosis and/or producers of hepato-carcinogenic
      mycotoxins. Salicylaldehyde (SA), a volatile natural compound, exhibited potent
      antifungal and anti-mycotoxigenic activities to A. flavus and A. parasiticus. By
      exposure to the volatilized SA, the growth of A. parasiticus was inhibited up to
      10-75% at 9.5 mM <= SA <= 16.0 mM, while complete growth inhibition was achieved
      at 19.0 mM <= SA. Similar trends were also observed with A. flavus. The aflatoxin
      production, i.e., aflatoxin B(1) and B(2) (AFB(1), AFB(2)) for A. flavus and
      AFB(1), AFB(2), AFG(1), and AFG(2) for A. parasiticus, in the SA-treated (9.5 mM)
      fungi was reduced by ~13-45% compared with the untreated control. Using gene
      deletion mutants of the model yeast Saccharomyces cerevisiae, we identified the
      fungal antioxidation system as the molecular target of SA, where sod1Delta
      [cytosolic superoxide dismutase (SOD)], sod2Delta (mitochondrial SOD), and
      glr1Delta (glutathione reductase) mutants showed increased sensitivity to this
      compound. Also sensitive was the gene deletion mutant, vph2Delta, for the
      vacuolar ATPase assembly protein, suggesting vacuolar detoxification plays an
      important role for fungal tolerance to SA. In chemosensitization experiments, co
      application of SA with either antimycin A or strobilurin (inhibitors of
      mitochondrial respiration) resulted in complete growth inhibition of Aspergillus
      at much lower dose treatment of either agent, alone. Therefore, SA can enhance
      antifungal activity of commercial antifungal agents required to achieve effective
      control. SA is a potent antifungal and anti-aflatoxigenic volatile that may have
      some practical application as a fumigant.

PMID- 20803258
TI  - TRPC expression in mesenchymal stem cells.
AB  - Transient receptor potential canonical (TRPC) channels are key players in calcium
      homeostasis and various regulatory processes in cell biology. Little is currently
      known about the TRPC subfamily members in mesenchymal stem cells (MSC), where
      they could play a role in cell proliferation. We report on the presence of TRPC1,
      2, 4 and 6 mRNAs in MSC. Western blot and immunofluorescence staining indicate a
      membrane and intracellular distribution of TRPC1. Furthermore, the decrease in
      the level of TRPC1 protein caused by RNA interference is accompanied by the
      downregulation of cell proliferation. These results indicate that MSC express
      TRPC1, 2, 4 and 6 mRNA and that TRPC1 may play a role in stem cell proliferation.

PMID- 20803259
TI  - Scientific research and the public trust.
AB  - This essay analyzes the concept of public trust in science and offers some
      guidance for ethicists, scientists, and policymakers who use this idea defend
      ethical rules or policies pertaining to the conduct of research. While the notion
      that  public trusts science makes sense in the abstract, it may not be
      sufficiently focused to support the various rules and policies that authors have
      tried to derive from it, because the public is not a uniform body with a common
      set of interests. Well-focused arguments that use public trust to support rules
      or policies for the conduct of research should specify (a) which public is being
      referred to (e.g. the general public or a specific public, such as a particular
      community or group); (b) what this public expects from scientists; (c) how the
      rule or policy will ensure that these expectations are met; and (d) why is it
      important to meet these expectations.

PMID- 20803260
TI  - Predicting outcomes of intermediate term complications and revisional surgery
      following laparoscopic adjustable gastric banding: utility of the CORE
      classification and Melbourne motility criteria.
AB  - BACKGROUND: Patients with laparoscopic adjustable gastric bands (LAGB) present at
      times with adverse symptoms or unsatisfactory weight loss, where a liquid
      contrast swallow or upper gastrointestinal endoscopy is not diagnostic. Stress
      barium and high resolution manometry are promising investigations, however, have
      not yet been established as clinically useful. METHODS: Patients with an
      unsatisfactory outcome following LAGB, where liquid contrast swallow and
      endoscopy were not diagnostic, were evaluated using high resolution video
      manometry and a stress barium. Pre-operative and follow-up clinical data were
      collected. Esophageal motility was assessed using the Melbourne criteria.
      RESULTS: There were 143 participants in the study. Stress barium identified the
      following appearances: gastric enlargement (n = 57), transhiatal enlargement (n =
      44), pan-esophageal dilatation (n = 9), and anatomically normal (n = 33). Twenty
      four (72%) of the anatomically normal patients had deficient esophageal motility.
      Revisional LAGB surgery was performed in 56 patients. This was successful in
      gastric enlargements when motility was intact (percentage of excess weight loss
      (%EWL) 58.3 +/- 16.2 vs. 35.4 +/- 19.7, p = 0.002). Revisional surgery for
      transhiatal enlargements improved symptoms but did not improve poor weight loss
      (%EWL 20.6 +/- 24.9 vs. 17.2 +/- 25, p = 0.1). CONCLUSIONS: The CORE
      classification combines anatomical change with esophageal motility and has been
      defined for intermediate term complications following LAGB where conventional
      investigations have not been diagnostic. Revisional LAGB surgery is helpful for
      patients with a gastric enlargement above the LAGB if esophageal motility is
      intact. If motility is deficient or there is an esophageal anatomical
      abnormality, intervention is not likely to remedy poor weight loss.

PMID- 20803261
TI  - Dilute Acid pretreatment of corncob for efficient sugar production.
AB  - Aqueous dilute acid pretreatments of corncob were conducted using cylindrical
      pressure vessels in an oil bath. Pretreatments were conducted in a temperature
      range of 160-190  degrees C with acid-solution-to-solid-corncob ratio of 2. The
      acid concentration (v/v) in the pretreatment solution was varied from 0% to 0.7%,
      depending on temperature. This gives acid charge on ovendry-weight corncob of 0
      2.58%. It was found that optimal pretreatment temperature is between 160 and 170 
      degrees C based on total xylose and glucose yields and thermal energy consumption
      in pretreatment. At 170  degrees C and acid charge of 2.2% on cob, total glucose
      yield and xylose recovery were 97% and 75%, respectively, which resulted in an
      overall monomeric sugar recovery of about 88%. Xylose concentration in the
      hydrolysate was about 12%, with xylose-to-acetic-acid ratio of 8 and to furan
      (furfural and hydroxymethylfurfural) of about 15.

PMID- 20803262
TI  - Kinetics of enzymatic high-solid hydrolysis of lignocellulosic biomass studied by
      calorimetry.
AB  - Enzymatic hydrolysis of high-solid biomass (>10% w/w dry mass) has become
      increasingly important as a key step in the production of second-generation
      bioethanol. To this end, development of quantitative real-time assays is
      desirable both for empirical optimization and for detailed kinetic analysis. In
      the current work, we have investigated the application of isothermal calorimetry
      to study the kinetics of enzymatic hydrolysis of two substrates (pretreated corn
      stover and Avicel) at high-solid contents (up to 29% w/w). It was found that the
      calorimetric heat flow provided a true measure of the hydrolysis rate with a
      detection limit of about 500 pmol glucose s(-1). Hence, calorimetry is shown to
      be a highly sensitive real-time method, applicable for high solids, and
      independent on the complexity of the substrate. Dose-response experiments with a
      typical cellulase cocktail enabled a multidimensional analysis of the
      interrelationships of enzyme load and the rate, time, and extent of the reaction.
      The results suggest that the hydrolysis rate of pretreated corn stover is limited
      initially by available attack points on the substrate surface (<10% conversion)
      but becomes proportional to enzyme dosage (excess of attack points) at later
      stages (>10% conversion). This kinetic profile is interpreted as an increase in
      polymer end concentration (substrate for CBH) as the hydrolysis progresses,
      probably due to EG activity in the enzyme cocktail. Finally, irreversible enzyme
      inactivation did not appear to be the source of reduced hydrolysis rate over
      time.

PMID- 20803263
TI  - Kinetics of lime pretreatment of sugarcane bagasse to enhance enzymatic
      hydrolysis.
AB  - The objective of this work was to determine the optimum conditions of sugarcane
      bagasse pretreatment with lime to increase the enzymatic hydrolysis of the
      polysaccharide component and to study the delignification kinetics. The first
      stage was an evaluation of the influence of temperature, reaction time, and lime
      concentration in the pretreatment performance measured as glucose release after
      hydrolysis using a 2(3) central composite design and response surface
      methodology. The maximum glucose yield was 228.45 mg/g raw biomass, corresponding
      to 409.9 mg/g raw biomass of total reducing sugars, with the pretreatment
      performed at 90 degrees C, for 90 h, and with a lime loading of 0.4 g/g dry
      biomass. The enzymes loading was 5.0 FPU/dry pretreated biomass of cellulase and
      1.0 CBU/dry pretreated biomass of beta-glucosidase. Kinetic data of the
      pretreatment were evaluated at different temperatures (60 degrees C, 70 degrees
      C, 80 degrees C, and 90 degrees C), and a kinetic model for bagasse
      delignification with lime as a function of temperature was determined. Bagasse
      composition (cellulose, hemicellulose, and lignin) was measured, and the study
      has shown that 50% of the original material was solubilized, lignin and
      hemicellulose were selectively removed, but cellulose was not affected by lime
      pretreatment in mild temperatures (60-90 degrees C). The delignification was
      highly dependent on temperature and duration of pretreatment.

PMID- 20803265
TI  - Nasal sinus leiomyosarcoma in a patient with history of non-hereditary unilateral
      treated retinoblastoma.
AB  - Hereditary patients with a history of treated retinoblastoma (RB) have a greatly
      increased risk of a broad spectrum of secondary malignancies appearing many years
      later, with a high incidence in the head and neck region. Leiomyosarcomas (LMS)
      account for up to 58% of these tumors. LMS in the sinonasal region generally are
      uncommon and are associated with a locally aggressive course and have a poor
      prognosis. RB may occur in two forms. The hereditary form is generally bilateral
      but can present unilaterally with a positive family history and typically
      exhibits a germline mutation in the RB1 gene on chromosome 13. The non-hereditary
      form is usually unilateral but can show the same germline mutation in up to 10%
      of cases. Patients with hereditary RB have been shown to have a significantly
      higher cumulative risk of developing secondary malignancies than those with the
      non-hereditary form (28 vs. 1.44% respectively). Most reported cases of sinonasal
      LMS are in patients with a history of the bilateral hereditary form of treated
      RB. We report a case of LMS of the nasal sinus area in a 35-year-old African
      American male with a history of non-hereditary unilateral RB and radiation
      therapy. To the best of our knowledge, this is the first reported case of
      sinonasal LMS arising in a patient with a history of non-hereditary unilateral
      RB. The clinical history, radiology, and pathology are presented along with a
      brief discussion of the literature.

PMID- 20803266
TI  - Novel hydroxypropyl-guar gellable lubricant eye drops for treatment of dry eye.
AB  - OBJECTIVE|: The objective of this review is to evaluate the safety and efficacy
      of polyethylene glycol 400/propylene glycol/hydroxypropyl-guar (Systane(r) Ultra
      [PEG/PG with HP-guar], Alcon Laboratories, Inc., Fort Worth, TX, USA) lubricant
      eye drops in reducing the signs and symptoms of dry-eye disease. METHODS|: A
      systematic literature search utilizing MEDLINE was conducted to identify peer
      reviewed articles related to dry-eye disease and PEG/PG with HP-guar lubricant
      eye drops. The search covered the period prior to October 2009. Additionally, a
      manual search based on citations in the published literature was conducted.
      RESULTS|: The PEG/PG with HP-guar artificial tears shows in-vitro viscoelastic
      properties with pH optimization. The pH of the solution adjusts to the pH of the
      ocular surface upon instillation, which results in tear film elasticity and
      viscosity similar to that of subjects without dry-eye disease. The reviewed
      literature demonstrated that this delivery system showed a reduction in corneal
      and conjunctival staining in dryeye disease, an improvement in tear film
      stability, a low coefficient of friction in an in-vitro model, and improved
      maintenance of best-corrected visual acuity over time. CONCLUSION|: A few small
      sized studies with short-term follow-up demonstrated that PEG/PG with HP-guar is
      a safe and effective lubricant eye drops for the treatment of dry-eye disease.
      Larger studies with longer duration are warranted to assess the long-term safety
      and efficacy of this formulation in patients with dry.eye disease.

PMID- 20803267
TI  - Editorial.

PMID- 20803268
TI  - Morphological analysis of microarterial media repair after 830 nm diode laser
      assisted end-to-end anastomosis: Comparison with conventional manual suture.
AB  - A series of 240 diode laser assisted end-to-end microvascular anastomoses (LAMA)
      and conventional manual anastomoses (CMA) were performed in the left and right
      common carotid of Wistar rats, respectively. In comparison with the two
      anastomotic methods, optic and scanning electron microscopic examinations were
      achieved from Day 0 to Day 210, in order to clarify the mechanism of media repair
      after diode laser welding, especially the long-term results. In the LAMA group,
      the cut vessel edges were welded without obvious thermal necrosis after laser
      treatment. On Day 10, media repair was underlined by circular bulges
      corresponding to the folds of cut vessel endings brought together. Inflammatory
      cells were regularly scattered in the adventitia in the vicinity of the
      anastomotic site, and were gaining ground intensively in the media by Day 20. At
      this time, the parallel organization of elastic laminae disappeared while the
      collagen network developed. On Day 120, irregular elastic fibres aggregated in
      the anastomotic site. On Day 210, reconstituted elastic lamina was present. In
      the CMA group, on Day 20, fibrotic repair appeared between cut vessel edges, and
      the injury incorporated by sutures was important. The elastic laminae were not
      reconstituted by Day 210 in any case. This microscopic study proves that the long
      term repair of diode LAMA facilitates media repair and prevents fibrotic scarring
      of the media.

PMID- 20803269
TI  - Dosedependent photodynamic effects of 9-acetoxy-2,7,12,17-tetrakis(?
      methoxyethyl)-porphycene in vitro.
AB  - Porphycenes are chemically pure photosensitizers for topical and systemic
      photodynamic therapy (PDT). Fast cellular uptake of 9-acetoxy-2,7,12,17-tetrakis
      (sB-methoxyethyl)porphycene (ATMPn) has been shown previously.HaCaT human
      keratinocytes were incubated with ATMPn (1 nmol l(-1) to 1 micromol l(-1) in DMSO
      or DOPC liposomes). After 1 h, cells were irradiated with different light doses
      (0, 24, 48J cm(-2)) using an incoherent light source (580-740 nm, 40 mW cm(-2)).
      Cytotoxic effects were determined by assessing the mitochondrial activity using
      the MTT assay 24 h following irradiation.Cytotoxic effects were dependent on
      ATMPn concentration and light dose. Using 20 nmol 1(-1), a 50% decrease of
      mitochondrial activity (EC(50)) after irradiation with 24 J cm(-2) was achieved.
      Lowering the ATMPn concentration (10nmol 1(-1)) and increasing the light dose (48
      J cm(-2)) yielded the same effect (EC(50)). Maximal decrease of mitochondrial
      activity (90%) was achieved using ATMPn concentrations of 50-100 nmol l(-1) and a
      light dose of 24 J cm(-2) or 25 nmol l(-1) ATMPn and 48 Jcm(-2).There was no
      difference regarding the dose-dependent cytotoxic effects using either ATMPn in
      DMSO or DOPC liposomes. In the control group (incubation with 1 nmol 1(-1) to
      1micromol 1(-1) ATMPn, no irradiation), dark toxicity was not observed.Cell
      photosensitization with ATMPn was very efficient in vitro yielding the maximal
      cytotoxic effect at very low ATMPn concentrations as compared to other
      photosensitizers. Since ATMPn in DMSO and DOPC liposomes revealed the same
      cytotoxic effects without dark toxicity, theDMSO formulation, which is much
      easier to prepare, will be preferred in future studies.

PMID- 20803270
TI  - XeCl laser ablation of biocompatible PTFE studied by photothermal beam
      deflection.
AB  - Laser beam deflection is a useful tool for studying the dynamics of the pulsed
      laser ablation mechanism, and has the advantage of being used as an in situ laser
      damage monitoring technique for both bulk and thin film polymeric and biological
      tissue samples. This work employs the photothermal deflection technique to study
      possible photo-acoustic phenomena during the excimer laser ablation of
      biocompatible polytetrafluoroethylene (PTFE) and to examine the crater surface
      quality by video microscopy.Although photo-acoustic phenomena are detected in the
      laser fluence threshold region, ablation is mainly the result of the photothermal
      process.

PMID- 20803271
TI  - Clinical effects of dynamic cooling during pulsed laser treatment of port-wine
      stains.
AB  - Pulsed dye lasers permit effective treatment of port-wine stains without a
      significant risk of complications. However, epidermal damage manifested by
      weeping or crusting of the treated area have been reported in 48-83% of patients,
      and transient hyperpigmentation after treatment is observed in 10-57%.
      Theoretically, the epidermis can be protected from thermal damage with the use of
      the concept of selective epidermal cooling.This study examined the clinical
      effects of rapid cooling of the epidermis with a liquid refrigerant R-134a
      (boiling point - 26.5 double daggerC) during pulsed dye laser therapy. In 23
      patients with port-wine stains, a 50-ms-long cooling pulse delivered immediately
      prior to laser irradiation with a fluence of 6.0 J cm(-2) significantly reduced
      the pain, and shortened the period with purpura without compromising the clinical
      blanching. Cooling periods longer than 60 ms, as well as additional cooling
      pulses immediately after laser exposure, reduced the blanching in areas
      irradiated with 6.0 J cm(-2).Post-treatment hyperpigmentation was not prevented
      with dynamic cooling.

PMID- 20803272
TI  - Smooth excimer laser coronary angioplasty (SELCA) and conventional excimer laser
      angioplasty: Comparison of vascular injury and smooth muscle cell proliferation.
AB  - Although the excimer laser, which utilizes 'non-thermal ablation effects', has
      achieved encouraging results in early clinical trials, the long-term results have
      failed to show any advantage over conventional percutaneous transluminal coronary
      angioplasty (PTCA).A new system, Smooth Excimer Laser Coronary Angioplasty
      (SELCA), has been developed to reduce the tissue damage in the vessel wall caused
      by shock waves and vapour bubbles.SELCA (wavelength 308 nm, pulse duration 115
      ns, repetition rate 150 Hz and energy density 50 mJ mm(-2)) lowers the amount of
      shock wave formation and pressure peak amplitude in the surrounding tissue by
      about eight times when compared to the conventional 308 nm excimer laser (ELCA).
      In this preclinical evaluation, this new system was compared to ELCA. Fifty New
      Zealand White rabbits were stimulated by repeated weak DC impulses for a period
      of 28 days in order to form an atherosclerotic plaque in the right carotid
      artery. The vessels were excised 3, 7,14 and 28 days after laser irradiation for
      immunohistochemical analysis.SELCA and ELCA laser treatment lead to a decrease in
      maximal intimal wall thickness 3 days after intervention (control: 177+/-4
      microm; SELCA: 131+/-22microm; ELCA: 120 +/-33microm). In the period between 3
      and 28 days, a moderate increase in intimal wall thickness was observed after
      SELCA treatment compared to a significant increase after ELCA (28 days after
      intervention: SELCA: 157+/-22microm; ELCA: 274 +/-28microm). Bromodeoxyuridine
      (BrdU) was applied 18 and 12 h before excision of the vessels in order to
      determine the percent of cells undergoing DNA synthesis. The percent of BrdU
      labelled SMC in the intima (control: 13 +/- 2 cells mm(-2)) increased in both
      groups after 3 days (SELCA: 248 +/- 107 cells mm(-2); ELCA: 162 +/- 41 cells mm(
      2)) and 7 days (SELCA: 162+/- 55 cells mm(-2); ELCA: 279 +/- 119 cells mm(
      2)).The present results demonstrate that vascular wall injury and increase in
      intimal wall thickness following SELCA are reduced in comparison to the results
      achieved with the conventional technique. Further trials are necessary to assess
      whether these improvements will lead to more favourable long-term results after
      excimer laser angioplasty.

PMID- 20803273
TI  - Characterization of a murine model for the rapid assessment of acute photodynamic
      response in tumour and muscle.
AB  - A murine implanted colorectal tumour model is described in which a measurement of
      tumour depth of necrosis is combined with a simultaneous measurement of muscle
      damage. The response of this model to a range of photodynamic therapy parameters
      was characterized using the chlorin photosensitizer mTHPC (temoporfin,
      Foscan(R)R). Both tumour depth of necrosis (measured directly and on histology)
      and muscle swelling correlate with the dose of photosensitizer and light, and are
      shown to be repeatable and consistent with published values obtained under
      similar conditions using established models.

PMID- 20803274
TI  - Laser doppler flowmetry in the hyperbaric environment.
AB  - Continuous monitoring of laser Doppler (LD) flowmetry was performed in eight
      healthy volunteers (mean age 42.0 + 12.1 yr; range 25-62 yr) before, during and
      after hyperbaric oxygenation ([HBO at 2.5 and 1.95 ATA (atmosphere
      absolute)]).Two models of the discrimination analysis are presented which allow
      classification, resulting from the parameter obtained by the LD flowmetry.The
      results show that 100% separation of the LD data under HBO at 2.5 and 1.95 ATA
      including five parameters can be achieved with the first model. The second model
      for the analysis of four different phases with eight parameters still shows an
      obvious separation; however, only 75% of the group integration is correct. In
      addition to transcutaneous P(2) measurements, which are sometimes difficult to
      obtain perfectly, LD parameters will be of interest to manage HBO treatment,
      especially when peripheral circulation is reduced.

PMID- 20803275
TI  - Longterm comparison of soft palate scars after UPPP made by CO(2), contact Nd-YAG
      or combined CO (2) and Nd-YAG laser beams.
AB  - C0(2) laser, contact Nd-YAG laser and Combolaser (combined CO(2) and Nd-YAG laser
      beam) vary distinctively in the way they interact with target tissue. To study
      the quality of mature scars produced by these lasers, the ultrastructure and
      amount of collagen in soft palate scars after 60 uvulopalatopharyngoplasty (UPPP)
      operations were analysed. The CO(2) laser was used in 19, contact Nd-YAG in 21
      and Combolaser in 20 operations. At a clinical follow-up examination carried out,
      on average, 51 (range 34-74) months postoperatively, a specimen was obtained from
      the soft palate scar for collagen analysis. Postoperative complaints of the
      patients were acknowledged. No differences between the laser groups were observed
      concerning the gross appearance of the scars or the amount and ultrastructure of
      collagen. Neither the frequency nor the quality of post-operative symptoms showed
      any differences between the lasers. Although the initial tissue effects are
      different, long-term remodelling produces nearly identical soft palate scars
      after the use of CO(2), contact Nd-YAG and Combolaser beams.

PMID- 20803276
TI  - In vivo temperature measurement during transcatheter endomyocardial Nd-YAG laser
      irradiation in dogs.
AB  - Intramural temperatures were monitored during catheter-directed endomyocardial
      non-contact laser irradiation by means of an array of thermocouples inserted
      epicardially. Via a novel electrode-laser catheter, a total of 30 Nd-YAG laser
      pulses, 1064 nm, 25 W/15 s, 20 W/30 s, 15 W/45 s,n = 10 each, were aimed at
      various endocardial sites in the ventricles of four dogs. Temperatures increased
      gradually after the onset of the laser pulses. Maximum values were measured in
      the central area of the irradiated spots: 100 +/- 15 double daggerC at 25 W, 78+/
      23 double daggerC at 20 W and 80 +/- 13 double daggerC at 15 W. Application of
      300 J of laser energy induced significantly higher temperatures at 25 W (p< 0.02)
      than at 20 or 15 W (20vs 15 W: p> 0.05). Initial temperature rise and lesion
      formation was accompanied by dwindling of local electrical potentials. There was
      no crater formation. Transcatheter non-contact Nd-YAG laser coagulation of
      healthy ventricular myocardium can be performed in a safe and controllable manner
      at power settings up to 20 W and laser energies up to 675 J.

PMID- 20803277
TI  - Photo-acoustic determination of optical parameters of tissue-like media with
      reference to opto-acoustic diffraction.
AB  - Tissue optical properties are determined by an interpretation of pressure
      transients generated by irradiation with pulsed laser light. These pressure
      signals are detected using piezo-electric transducers.These signals are
      influenced by numerous processes during generation, propagation and detection.
      Specific experiments were performed to study each process in particular using
      different substances with various absorption and scattering properties.Opto
      acoustical diffraction effects cause a strong distortion of the shape of the
      transients. This phenomenon was investigated experimentally and verified
      theoretically.

PMID- 20803278
TI  - Enhancement of tissue lesion depth by dual wavelength irradiation with the Nd
      YAG/KTP laser: Perspectives for laser prostatectomy.
AB  - The Nd-YAG/KTP laser coagulates and vaporizes prostate tissue. The objective of
      this study was to investigate the combined effects of both wavelengths and to
      determine the irradiation parameters allowing the largest lesion volume. Chicken
      breast tissue was irradiated ex vivo. Consecutive 1064 and 532 nm Nd-YAG/KTP
      laser irradiations were performed for different combinations (30 W/10 W, 20 W/20
      W, 10 W/30 W) with variable total fluence (1200 J, 2400 J, 3600 J) and compared
      to isofluent single wavelengths at 40 W irradiation. The depths, diameters and
      volumes of the total lesion as well as the vaporization effects of the 532 nm
      wavelength on normal and on priorly coagulated tissue were analysed. Maximum
      total lesion depths (p< 0.001) were found under combined Nd-YAG/KTP (20 W/20 W)
      irradiation conditions. Ablation efficacy of the 532 nm wavelength was reduced
      after prior 1064 nm irradiation, but crater depths were increased. Dual
      wavelength irradiation with the Nd-YAG/KTP laser induces a specific denaturation
      process. This may represent a new approach to increase the depth of coagulation
      necrosis, and thus the treated volume, thereby improving long-term results.

PMID- 20803279
TI  - Letter to the editors.

PMID- 20803280
TI  - New laser literature.

PMID- 20803281
TI  - [Geriatrics and radiation oncology. Part 1: How to identify high-risk patients
      and basic treatment principles].
AB  - BACKGROUND: Until the mid of this century, 33% of the Western population will be
      > or = 65 years old. The percentage of patients being > or = 80 years old with
      today 5% will triple until 2050. Therefore, radiation oncologists must be
      familiar with special geriatric issues to meet the increasing demand for
      multidisciplinary cooperation and to offer useful and individual treatment
      concepts. PATIENTS AND METHODS: This review article will provide basic data on
      the definition, identification and treatment of geriatric cancer patients.
      RESULTS: The geriatric patient is defined by typical multimorbidity (15 items)
      and by age-related increased vulnerability. Best initial identification of
      geriatric patients will be provided by assessment including the Barthel Index
      evaluating self-care and activity in daily life, by the Mini-Mental Status Test
      that will address cognitive pattern, and by the Timed "Up&Go" Test for evaluation
      of mobility. As for chemotherapy, standard treatment was associated with
      increased toxicity, consequently, dose modifications and supportive treatment are
      of special importance. CONCLUSION: Geriatric cancer patients need to be
      identified by special assessment instruments. Due to increased toxicity following
      chemotherapy, supportive measures seem important. Radiation treatment as a
      noninvasive and outpatient-based treatment remains an important and preferable
      option.

PMID- 20803282
TI  - Tumor shrinkage assessed by volumetric MRI in the long-term follow-up after
      stereotactic radiotherapy of meningiomas.
AB  - PURPOSE: To evaluate tumor volume reduction in the follow-up of meningiomas after
      fractionated stereotactic radiotherapy (FSRT) or linac radiosurgery (RS) by using
      magnetic resonance imaging (MRI). PATIENTS AND METHODS: In 59 patients with skull
      base meningiomas, gross tumor volume (GTV) was outlined on contrast-enhanced MRI
      before and median 50 months (range 11-92 months) after stereotactic radiotherapy.
      MRI was performed as an axial three-dimensional gradient-echo T1-weighted
      sequence at 1.6 mm slice thickness without gap (3D-MRI). Results were compared to
      the reports of diagnostic findings. RESULTS: Mean tumor size of all 59
      meningiomas was 13.9 ml (0.8-62.9 ml) before treatment. There was shrinkage of
      the treated meningiomas in all but one patient. Within a median volumetric follow
      up of 50 months (11-95 months), an absolute mean volume reduction of 4 ml (0-18
      ml) was seen. The mean relative size reduction compared to the volume before
      radiotherapy was 27% (0-73%). Shrinkage measured by 3D-MRI was greater at longer
      time intervals after radiotherapy. The mean size reduction was 17%, 23%, and 30%
      (at < 24 months, 24-48 months, and 48-72 months). CONCLUSION: By using 3D-MRI in
      almost all patients undergoing radiotherapy of a meningioma, tumor shrinkage is
      detected. The data presented here demonstrate that volumetric assessment from 3D
      MRI provides additional information to routinely used radiologic response
      measurements. After FSRT or RS, a mean size reduction of 25-45% can be expected
      within 4 years.

PMID- 20803283
TI  - [The significance of radiation therapy for symptomatic vertebral hemangiomas
      (SVH)].
AB  - PURPOSE: To evaluate the efficacy of radiation therapy (RT) for symptomatic
      vertebral hemangioma (SVH). MATERIAL AND METHODS: Based on the Registry for Rare
      Benign Disorders (RRBD) of the German Cooperative Group on Radiation Therapy for
      Benign Diseases (GCG-BD), the clinical information, treatment plans and outcome
      data from seven cooperating German RT institutions were analyzed retrospectively.
      RESULTS: Over a period of 39 years (1969-2008), a total of 84 patients with 96
      symptomatic lesions underwent RT. The predominant indication was pain in 97.6%,
      and, in addition, 28.6% of patients had neurological deficits. The median total
      dose was 34 Gy (4.5-45 Gy), and the median single dose 2.0 Gy (0.5-3.0 Gy). After
      a median follow-up of 68 months (6-422 months), complete symptom relief (CR)
      occurred in 61.9% of patients, 28.6% had partial relief, and 9.5% had no relief
      (NR). The overall response rate (CR + PR) was 90.5%. In 26.2% of patients,
      radiologic signs of remineralization were noted. After a median follow-up of 70
      months (8-124 months), symptom progression occurred in eight patients (9.5%).
      Therefore, the long-term rate of local control was 80.9%. Multivariate
      statistical analysis revealed a significantly higher rate of symptom relief and
      local control for total doses > or = 34 Gy. Side effects > RTOG/EORTC grade 2
      were not observed. CONCLUSION: RT is a safe and effective for treatment of SVH.
      Total doses of at least 34 Gy are recommended to achieve optimal treatment
      response.

PMID- 20803284
TI  - Evaluation of CEM43 degrees CT90 thermal dose in superficial hyperthermia: a
      retrospective analysis.
AB  - BACKGROUND AND PURPOSE: Prospective use of the CEM43 degrees CT90 thermal dose
      parameter has been proposed for hyperthermia treatments. This study evaluates the
      CEM43 degrees CT90 parameter by means of a retrospective analysis of recurrent
      breast cancer patients receiving reirradiation plus hyperthermia. MATERIAL AND
      METHODS: CEM43 degrees CT90 was calculated for 72 patients who received 8 x 4 Gy
      reirradiation plus 8 x 1 h hyperthermia for adenocarcinoma recurrences at the
      chest wall. Associations of prognostic factors CEM43 degrees CT90 and tumor
      maximum diameter with endpoints complete response (CR), duration of local control
      (DLC), and overall survival (OS) were determined. RESULTS: A highly significant
      inverse association between CEM43 degrees CT90 and tumor maximum diameter (rho = 
      0.7, p < 1e-6) was found. The association between CR and CEM43 degrees CT90 was
      not significant (p > or = 0.7). CEM43 degrees CT90 was associated with DLC. Both
      CEM43 degrees CT90 and tumor maximum diameter had a significant association with
      survival (p < or = 0.01). The association with thermal dose, when adjusted for
      tumor maximum diameter, was not significant for either CR, DLC, or OS (p > 0.2).
      CONCLUSION: In this retrospective study, no clear CEM43 degrees CT90 thermal dose
      targets or associations with clinical endpoints could be established.

PMID- 20803285
TI  - Radiobiological comparison of hypofractionated accelerated partial-breast
      irradiation (APBI) and single-dose intraoperative radiotherapy (IORT) with 50-kV
      X-rays.
AB  - BACKGROUND AND PURPOSE: Intraoperative radiotherapy (IORT) of the tumor bed in
      early breast cancer is presently performed with a single dose of 50-kV X-rays
      from a miniaturized X-ray machine using spherical applicators. The purpose was to
      model the biological effect of hypofractionated accelerated partial-breast
      irradiation (APBI) with ten fractions. MATERIAL AND METHODS: The relative
      biologic effectiveness (RBE) was estimated from the linear-quadratic (L-Q)
      formalism including repair of sublethal damage or assuming a constant RBE = 1.2
      1.5. The radial distribution of biological effect was assessed from clinical dose
      response curves. In accordance with clinical convention, the dose for APBI was
      prescribed at 1 cm depth in the tumor bed, whereas for IORT it was prescribed at
      the applicator surface. RESULTS: The fraction size was fitted to give the same
      risk of late normal-tissue reaction (fibrosis) as single-dose IORT with a maximum
      dose of 20 Gy. The isoeffective fraction size at 1 cm depth varied between 1.01
      Gy for RBE estimated from the L-Q model and 1.64 Gy for constant RBE. The
      applicator size and dose prescription point influenced the radial dose
      distribution. The "sphere of equivalence" within which the risk for local
      recurrence is the same for whole-breast radiotherapy was predicted to extend to
      11-15 mm distance from the applicator for alpha/beta = 10 Gy and 9-13 mm for
      alpha/beta = 4 Gy for hypofractionated APBI, representing an increase of the
      sphere of equivalence by 2.5-6 mm relative to single-dose IORT. CONCLUSION: An
      increase of the therapeutic window with hypofractionated APBI relative to single
      dose IORT should be feasible.

PMID- 20803287
TI  - Radiolabeled cetuximab plus whole-brain irradiation (WBI) for the treatment of
      brain metastases from non-small cell lung cancer (NSCLC).
AB  - BACKGROUND AND PURPOSE: The addition of systemic drugs to whole-brain irradiation
      has not improved the survival of patients with multiple brain metastases, most
      likely because the agents did not readily cross the blood-brain barrier (BBB).
      Radiolabeling of cetuximab was performed to investigate whether this antibody
      crosses the BBB. CASE REPORT: A patient with multiple brain lesions from non
      small cell lung cancer was investigated. The largest metastasis (40 x 33 x 27 mm)
      was selected the reference lesion. On day 1, 200 mg/m(2) cetuximab (0.25% hot and
      99.75% cold antibody) were given. On day 3, 200 mg/m(2) cetuximab (cold antibody)
      were given. Weekly doses of 250 mg/m(2) cetuximab were administered for 3 months.
      RESULTS: The reference lesion showed enhancement of radiolabeled cetuximab
      ((123)I-Erbi) on scintigraphy; (123)I-Erbi crossed the BBB and accumulated in the
      lesion. The reference lesion measured 31 x 22 x 21 mm at 4 months. Enhancement of
      contrast medium was less pronounced. CONCLUSION: This is the first demonstration
      of cetuximab crossing the BBB and accumulating in brain metastasis.

PMID- 20803286
TI  - Aplastic anemia as a cause of death in a patient with glioblastoma multiforme
      treated with temozolomide.
AB  - BACKGROUND: Standard treatment of glioblastoma multiforme consists of
      postoperative radiochemotherapy with temozolomide, followed by a 6-month
      chemotherapy. Serious hematologic complications are rarely reported. CASE REPORT
      AND RESULTS: The authors present the case of a 61-year-old female patient with
      glioblastoma multiforme treated with external-beam radiation therapy and
      concomitant temozolomide. After completion of treatment, the patient developed
      symptoms of serious aplastic anemia that eventually led to death due to prolonged
      neutro- and thrombocytopenia followed by infectious complications. CONCLUSION:
      Lethal complications following temozolomide are, per se, extremely rare, however,
      a total of four other cases of aplastic anemia have been reported in the
      literature so far.

PMID- 20803288
TI  - Distribution and enrichment of silver and cadmium in coastal sediments from Bahia
      Todos Santos, Baja California, Mexico.
AB  - Silver, cadmium and iron were studied in sediment from Bahia Todos Santos, Baja
      California, Mexico during 2004. Results showed that the spatial distributions of
      these metals were very similar to that of organic carbon and fine grain size,
      with values increasing from the inner to the outer parts of the bay. High
      concentrations and enrichments of silver (0.051-0.071 MUg g-1 dry weight) and
      cadmium (1.9 MUg g-1 dry weight) in Bahia Todos Santos were associated to harbor
      dredging activities and to coastal upwelling, respectively. However, the
      distribution of silver and cadmium in most of the study area is controlled by
      grain size and organic carbon content.

PMID- 20803290
TI  - Unicellular cyanobacteria with a new mode of life: the lack of photosynthetic
      oxygen evolution allows nitrogen fixation to proceed.
AB  - Some unicellular N(2)-fixing cyanobacteria have recently been found to lack a
      functional photosystem II of photosynthesis. Such organisms, provisionally termed
      UCYN-A, of the oceanic picoplanktion are major contributors to the global marine
      N-input by N(2)-fixation. Since their photosystem II is inactive, they can
      perform N(2)-fixation during the day. UCYN-A organisms cannot be cultivated as
      yet. Their genomic analysis indicates that they lack genes coding for enzymes of
      the Calvin cycle, the tricarboxylic acid cycle and for the biosynthesis of
      several amino acids. The carbon source in the ocean that allows them to thrive in
      such high abundance has not been identified. Their genomic analysis implies that
      they metabolize organic carbon by a new mode of life. These unicellular N(2)
      fixing cyanobacteria of the oceanic picoplankton are evolutionarily related to
      spheroid bodies present in diatoms of the family Epithemiaceae, such as
      Rhopalodia gibba. More recently, spheroid bodies were ultimately proven to be
      related to cyanobacteria and to express nitrogenase. They have been reported to
      be completely inactive in all photosynthetic reactions despite the presence of
      thylakoids. Sequence data show that R. gibba and its spheroid bodies are an
      evolutionarily young symbiosis that might serve as a model system to unravel
      early events in the evolution of chloroplasts. The cell metabolism of UCYN-A and
      the spheroid bodies may be related to that of the acetate photoassimilating green
      alga Chlamydobotrys.

PMID- 20803289
TI  - Level of heavy metals in some edible marine fishes of mangrove dominated tropical
      estuarine areas of Hooghly River, north east coast of Bay of Bengal, India.
AB  - The muscles of some important marine fishes collected in and around Hooghly
      estuarine coastal areas were analyzed for the heavy metals Cu, Zn, Ni, Cd, Cr and
      Pb. The concentration range of Cu (16.22-47.97 ppm), Pb (12.40-19.96 ppm) and Zn
      (12.13-44.74 ppm) were recorded comparatively higher and were similar to that
      found in contaminated areas. On the other hand the ranges of Ni (2.20-3.69 ppm),
      Cr (0-3.89 ppm) and Cd (0.62-1.20 ppm) were almost equal to those carried out
      over a wide range of geographical areas. The degree of bioaccumulations was metal
      specific as well as species-specific in nature. The toxic groups of metals (Pb
      and Cd) showed higher variability than the essential metals (Cu, Zn and Ni). The
      calculated intake value of metals (week-1 kg-1 body wt) varied from 14.88 to
      27.60 of Pb, 0.87 to 1.68 of Cd, 0.0 to 5.45 of Cr, 22.70 to 137.16 of Cu, 3.08
      to 5.17 of Ni and 16.98 to 62.60 of Zn through human consumption of these fishes
      and were compared with those of standard Provisional Tolerable Weekly Intake
      value (PTWI) per kg body weight as stipulated by WHO. The PTWI(Cal) values of Pb
      in some of the fishes recorded marginally excess values and may indicate a health
      risk through consumption of successive 7 days in a week.

PMID- 20803291
TI  - Risk of upper gastrointestinal tract events in risedronate users switched to
      alendronate.
AB  - Upper gastrointestinal (GI) side effects are a known complication of therapy with
      oral aminobisphosphonates, but it is currently unclear if bisphosphonate type or
      formulation influences the risk of developing side effects. Here, we performed a
      retrospective cohort study to determine if patients who switched from weekly
      risedronate to weekly alendronate had an increased risk of upper GI side events.
      The study utilized The Health Improvement Network (THIN) database, which
      contained anonymous medical records from 390 general practices in the United
      Kingdom. The study was performed following the introduction of generic
      alendronate preparations, by which point 94% of alendronate prescriptions were
      for the generic formulation. We identified 3,446 patients who had been stabilized
      on risedronate 35 mg/week, of whom 530 were switched to alendronate 70 mg/week.
      The risk of developing a GI adverse event was higher in patients who switched to
      alendronate compared with those who remained on risedronate (hazard ratio [HR] =
      1.85, 95% confidence interval [CI] 1.26-2.72). The risk was even greater in the
      subgroup of patients with a history of upper GI events (HR = 3.18, 95% CI 2.79
      3.63) but was also observed in patients with no history of GI events (HR = 1.76,
      95% CI 1.15-2.69). We conclude that switching patients who are stabilized on
      risedronate to alendronate is associated with an increased risk of GI adverse
      effects. This could lead to reduced compliance and reduced therapeutic
      effectiveness, which might offset the cost savings of using the generic
      formulation.

PMID- 20803292
TI  - Bone morphogenetic protein-7 promotes chondrogenesis in human amniotic epithelial
      cells.
AB  - Bone morphogenetic proteins (BMPs) play important roles at multiple stages of
      chondrogenesis. This study was undertaken to investigate the potential role of
      bone morphogenetic protein-7 (BMP-7) in the differentiation of chondrocytes using
      tissue engineering techniques. The impact of BMP-7 on human amniotic epithelial
      cells (hAECs) was tested. The hAECs were treated either with recombinant human
      BMP-7 cDNA or with transforming growth factor beta 1 (TGF-beta1) as a positive
      control for three weeks in vitro. Cartilaginous differentiation and proliferation
      were assayed by quantitative RT-PCR, histology, and in situ hybridization. Our
      results were such that hAECs treated with either BMP-7 or TGF-beta1 expressed
      cartilage markers (aggrecan, Sox9, CEP-68, and type II and X collagens) within
      three weeks. Compared with a control vector, BMP-7 induced a decrease in type I
      collagen expression, while the transcription of the cartilage-specific type II
      collagen remained stable. In induction experiments, BMP-7 transgenic hAECs
      exhibited the largest amount of matrix synthesis. In conclusion, these data
      indicate that BMP-7 plays an important role in inducing the production of
      cartilage by hAECs in vitro. Cartilage differentiation and matrix maturation can
      be promoted by BMPs in a cartilage engineering paradigm. These properties make
      BMPs promising tools in the engineering of cartilaginous joint bio-prostheses and
      as candidate biological agents or genes for cartilage stabilisation.

PMID- 20803293
TI  - Comparison of fixator-assisted nailing versus circular external fixator for bone
      realignment of lower extremity angular deformities in rickets disease.
AB  - PURPOSE: In rickets patients, limb deformities are usually multiapical and
      complex even with medical treatment; residual deformities remain necessitating
      surgical correction. In our study we aim to compare the results of correction of
      lower limb deformities, in rickets patients, treated with circular external
      fixator versus fixator-assisted intra-medullary nail. MATERIALS AND METHODS:
      Seventeen rickets patients, with 39 deformed lower extremity segments (femur and
      or tibia), underwent deformity correction procedures in our institution. Ten
      patients with 26 segments were treated using fixator-assisted nailing. Nine
      patients with 17 segments were treated using Ilizarov technique with circular
      frame. All patients were evaluated by long-standing true anteroposterior and
      lateral orthoroentgenograms of lower extremities preoperatively. Joint alignment,
      joint orientation, and apices of deformities were calculated and noted. The
      postoperative results of MAD, MPTA, LDFA, PPPTA and functional criteria were
      compared with preoperative values and assessments made in SPSS 13.0 for Windows
      by using McNemar, Pearson Chisquare, and Fisher exact statistical tests. RESULTS:
      Mean age for the fixator-assisted nailing (FAN) group patients at the time of
      surgery was 23.8 years (14-37 years). There were 16 femur and 10 tibiae operated
      on 6 female and 4 male patients. The mean follow up time is 42.6 months (6-71
      months). In the Ilizarov group patients the mean age at the time of surgery was
      16.7 years (13-22 years). There were 14 tibiae and 3 femur operated on 6 female
      and 3 male patients. The mean follow-up time was 19 months (6-48 months). Results
      were evaluated according to the Paley et al. classification of bone and
      functional results. According to those criteria we had 1 fair, 1 good, and 7
      excellent bone results and 1 fair, 1 good, and 7 excellent functional results in
      the circular ring fixator group. In the FAN group we found 3 good and 7 excellent
      bone results; 1 fair, 2 good, and 7 excellent functional results. Nearly all
      patients complained of pain, limping, instability, and walking problems at their
      first preoperative visit. In both groups there was no union problem; in the FAN
      group, in one patient correction loss occurred and in another one screw loosening
      was encountered; in the Ilizarov group, 66% of patients had pin tract infections
      and one premature fibula consolidation occurred. Statistical analysis revealed no
      significant difference between two groups in correction ratios.(pearson chi
      square p = 0.332 for MAD; pearson chi square p = 0.477 for LDFA; Paley functional
      criteria fisher exact p = 0.684). CONCLUSION: The results indicated that fixator
      assisted nailing carries deformity correction accuracy comparable with Ilizarov
      type external fixators. FAN provides great patient comfort and the total
      treatment time is less. In patients with rickets, the retained IM nail can
      further provide protection against recurrence even if the metabolic pathology
      reoccurs.

PMID- 20803294
TI  - Normobaric hypoxia and sports: the debate continues.

PMID- 20803295
TI  - Eye-lens accommodation load and static trapezius muscle activity.
AB  - The purpose of this experimental study was to investigate if sustained periods of
      oculomotor load impacts on neck/scapular area muscle activity. The static
      trapezius muscle activity was assessed from bipolar surface electromyography,
      normalized to a submaximal contraction. Twenty-eight subjects with a mean age of
      29 (range 19-42, SD 8) viewed a high-contrast fixation target for two 5-min
      periods through: (1) -3.5 dioptre (D) lenses; and (2) 0 D lenses. The target was
      placed 5 D away from the individual's near point of accommodation. Each subject's
      ability to compensate for the added blur was extracted via infrared
      photorefraction measurements. Subjects whose accommodative response was higher in
      the -D blur condition (1) showed relatively more static bilateral trapezius
      muscle activity level. During no blur (2) there were no signs of relationships.
      The results indicate that sustained eye-lens accommodation at near, during
      ergonomically unfavourable viewing conditions, could possibly represent a risk
      factor for trapezius muscle myalgia.

PMID- 20803296
TI  - Intragenic deletions and a deep intronic mutation affecting pre-mRNA splicing in
      the dihydropyrimidine dehydrogenase gene as novel mechanisms causing 5
      fluorouracil toxicity.
AB  - Dihydropyrimidine dehydrogenase (DPD) is the initial enzyme acting in the
      catabolism of the widely used antineoplastic agent 5-fluorouracil (5FU). DPD
      deficiency is known to cause a potentially lethal toxicity following
      administration of 5FU. Here, we report novel genetic mechanisms underlying DPD
      deficiency in patients presenting with grade III/IV 5FU-associated toxicity. In
      one patient a genomic DPYD deletion of exons 21-23 was observed. In five patients
      a deep intronic mutation c.1129-5923C>G was identified creating a cryptic splice
      donor site. As a consequence, a 44 bp fragment corresponding to nucleotides
      c.1129-5967 to c.1129-5924 of intron 10 was inserted in the mature DPD mRNA. The
      deleterious c.1129-5923C>G mutation proved to be in cis with three intronic
      polymorphisms (c.483 + 18G>A, c.959-51T>G, c.680 + 139G>A) and the synonymous
      mutation c.1236G>A of a previously identified haplotype. Retrospective analysis
      of 203 cancer patients showed that the c.1129-5923C>G mutation was significantly
      enriched in patients with severe 5FU-associated toxicity (9.1%) compared to
      patients without toxicity (2.2%). In addition, a high prevalence was observed for
      the c.1129-5923C>G mutation in the normal Dutch (2.6%) and German (3.3%)
      population. Our study demonstrates that a genomic deletion affecting DPYD and a
      deep intronic mutation affecting pre-mRNA splicing can cause severe 5FU
      associated toxicity. We conclude that screening for DPD deficiency should include
      a search for genomic rearrangements and aberrant splicing.

PMID- 20803297
TI  - Clonal and territorial development of the pancreas as revealed by eGFP-labelled
      mouse chimeras.
AB  - The clonal structure of the pancreas was analysed in neonatal and adult mouse
      chimeras in which one partner displayed cell patches expressing green fluorescent
      protein (eGFP). Coherent growth during pancreatic histogenesis was suggested by
      the presence of large eGFP-labelled acinar clusters rather than a scattered
      distribution of individual labelled acinar cells. The adult chimeric pancreas
      contained monophenotypic acini, whereas surprisingly 5% of acini in neonates were
      polyclonal. Monophenotypic acini presumably arose by coherent expansion leading
      to large 3D patches and may not be monoclonal. Islets of Langerhans were
      oligoclonal at both ages investigated. The proportion of eGFP positive cells
      within islets did not correlate with that of the surrounding acinar tissue
      indicating clonal independence of islets from their neighbourhood. The patterns
      observed argue against a secondary contribution of blood-borne progenitor/stem
      cells to the acinar compartment during tissue turnover. The different clonal
      origins of acini and islets are integrated into a model of pancreatic
      histogenesis.

PMID- 20803298
TI  - Long-term outcome of nephropathic cystinosis: a 20-year single-center experience.
AB  - Nephropathic cystinosis (NC) is a severe disease that is complicated by early
      onset chronic renal failure (CRF) and other complications related to cystine
      deposition in tissue. Since the 1980s, the prognosis of NC has dramatically
      improved after the introduction of cysteamine treatment. Limited data are
      available documenting improvement in prognosis. We reviewed our long-term data
      (follow-up 6.3-27.8 years) on 23 patients followed in the past 26 years. Overall,
      stage III CRF was reached at 10 years of age in >90% of patients, whereas >80%
      reached end-stage renal disease before the age of 14 years. Three patients died
      during the follow-up. Our analysis shows a clear improvement in renal outcome (p
      = 0.001) and linear growth (p = 0.04) in patients treated more recently.
      Improvement in the evolution of renal function was significantly associated with
      early initiation of cysteamine (p = 0.006), with the dose of cysteamine (p =
      0.04), and with the use of angiotensin-converting enzyme inhibitors (p = 0.01).
      Nonrenal long-term complications are similar to previously reported data. Of
      note, 3/23 patients developed rare forms of primary tumors that were successfully
      treated. In conclusion, our experience shows a significant improvement in the
      renal and nonrenal complications of cystinosis over the past decades and
      highlights the importance of early diagnosis in order to initiate cysteamine as
      soon as possible.

PMID- 20803299
TI  - Atypical hemolytic uremic syndrome associated with H1N1 influenza A virus
      infection.

PMID- 20803300
TI  - Levetiracetam for levodopa-induced dyskinesia in Parkinson's disease: a
      randomized, double-blind, placebo-controlled trial.
AB  - The aim of this study was to assess the efficacy, safety and tolerability of the
      antiepileptic compound levetiracetam (LEV) for the treatment of levodopa-induced
      dyskinesia (LID) in Parkinson's disease (PD). We thus performed a randomized,
      double-blind, placebo-controlled, parallel-group pilot study in PD patients with
      moderate-to-severe LID on stable dopaminergic therapy. Placebo or LEV was
      administered twice daily (titrated from 250 to 2,000 mg/day) as add-on therapy.
      Subjects underwent evaluation of the unified-PD-rating scale (UPDRS) and the
      modified abnormal involuntary movement scale (AIMS). The primary outcome variable
      was the change of the AIMS score between baseline and end-of-treatment visit.
      Secondary variables included total UPDRS score and response to levodopa
      challenge. Of 32 randomized patients (mean age 65.2 years, 62.5% women), 17
      received LEV and 15 placebo. After 11 weeks of treatment, mean changes of the
      modified AIMS from baseline were -1.5 (-26%) for LEV (p = 0.332) and +0.9 (+13%)
      for placebo (p = 0.588) without significant differences between groups. Mean
      changes of the UPDRS item 32/33 sum score from baseline showed significant
      improvement of dyskinesia in the LEV group [-1.0 (-20%); p = 0.012], but not in
      the placebo group [-0.4 (-8%); p = 0.306]. Treatment had no effects on UPDRS
      motor score or levodopa response. Frequency and quality of adverse events were
      similar in both treatment groups. Together, LEV showed only mild antidyskinetic
      effects without worsening of Parkinsonian symptoms or compromising levodopa
      efficacy. LEV was well tolerated in doses up to 2,000 mg/day. Further large
      controlled studies are warranted to evaluate the impact of LEV on LID in PD
      patients.

PMID- 20803302
TI  - Theory of microphase separation in crosslinked polymer blends immersed in a theta
      solvent.
AB  - The aim of this work is a theoretical study of the effects of the solvent quality
      on the microphase separation in crosslinked polymer blends, from a static and
      kinetics point of view. More precisely, we assume that the crosslinked mixture is
      trapped in a theta-solvent. The static microphase properties are studied through
      the static structure factor. The latter is computed using an extended blob model,
      where the crosslinked unlike chains can be viewed as sequences of blobs. We
      demonstrate that the presence of the theta-solvent simply leads to a
      multiplicative renormalization of these properties, and the renormalization
      factors are powers of the overall monomer volume fraction. Second, we investigate
      the early kinetics of the microphase separation, via the relaxation rate, tau(q),
      which is a function of the wave number q (at fixed temperature and monomer volume
      fraction). We first show that the kinetics is entirely controlled by local
      motions of Rouse type, since the slow motions are frozen out by the presence of
      crosslinks. Using the blob model, we find an explicit form for the growth rate
      Omega(q) = tau(q)-1, which depends, in addition to the wave number q , on the
      overall monomer volume fraction, Phi. Also, we discuss the effect of initial
      entanglements that are trapped when the system is crosslinked. In fact, these
      play the role of true reticulation points, and then, they quantitatively
      contribute to the microseparation phenomenon. Finally, the results are compared
      to their homologous relatively to the molten state and to the good solvent case.
      The main conclusion is that the quality of the solvent induces drastic changes of
      the microphase properties.

PMID- 20803301
TI  - Thought disorders among non-demented outpatients with Parkinson's disease:
      prevalence and associated factors.
AB  - The objectives of the study are to evaluate the prevalence and the associated
      factors of thought disorders in a large cross-sectional population of non
      demented out patients with Parkinson's disease (PD). Four-hundred and nineteen
      consecutive non-demented PD patients were studied through the DoPaMiP cross
      sectional study. Demographic and clinical variables were recorded, including
      motor and cognitive status, dependency, depressive and anxious symptoms,
      dysautonomia and sleep disorders. The presence of thought disorders over the past
      15 days was assessed by the Unified Parkinson's Disease Rating Scale part I.
      Patients with and without thought disorders were compared using parametric tests.
      Logistic regression was applied to significant data. Thought disorders were
      present in 105 patients (25%) including vivid dreams in 83 (19.8%), benign
      hallucinations in 17 (4.1%), and hallucinations without insight in 5 (1.2%). No
      patient had delusion. Patients with thought disorders were more dependent than
      the others. Thought disorders were associated with longer PD duration, greater
      UPDRS scores and the presence of motor complications. Conversely, UPDRS tremor
      sub-score was lower in patients without thought disorders. Thought disorders were
      also associated with dysautonomia, lower MMSE score, depression and sleep
      disorders. Logistic regression identified PD duration, lower MMSE score,
      depressive and dysautonomic signs as independent risk factors. In conclusion,
      mild thought disorders were present in 25% of non-demented outpatients with PD,
      but hallucinations were present in 5% only. Thought disorders were associated
      with PD duration, depressive and dysautonomic symptoms and lower MMSE score.

PMID- 20803303
TI  - Drag forces on inclusions in classical fields with dissipative dynamics.
AB  - We study the drag force on uniformly moving inclusions which interact linearly
      with dynamical free field theories commonly used to study soft condensed matter
      systems. Drag forces are shown to be nonlinear functions of the inclusion
      velocity and depend strongly on the field dynamics. The general results obtained
      can be used to explain drag forces in Ising systems and also predict the
      existence of drag forces on proteins in membranes due to couplings to various
      physical parameters of the membrane such as composition, phase and height
      fluctuations.

PMID- 20803304
TI  - Supratentorial and cerebellar liponeurocytomas: report of four cases with review
      of literature.
AB  - Liponeurocytoma is not exclusive to the cerebellar or fourth ventricular
      location. Since its inclusion in the central nervous system tumor classification
      in 2000, six cases with similar radiological, histomorphological and
      immunohistochemical features have also been described in the lateral ventricles.
      In the present study, we report clinical, radiological and pathological findings
      of three supratentorial and one cerebellar liponeurocytoma from our records,
      evaluated with an extensive panel of immunohistochemistry, and review published
      cases in the literature. The immunohistochemical pattern of supratentorial and
      infratentorial liponeurocytomas are almost identical, which indicates that these
      tumors are homologous.

PMID- 20803305
TI  - Glioblastoma-derived spheroid cultures as an experimental model for analysis of
      EGFR anomalies.
AB  - Glioblastoma cell cultures in vitro are frequently used for investigations on the
      biology of tumors or new therapeutic approaches. Recent reports have emphasized
      the importance of cell culture type for maintenance of tumor original features.
      Nevertheless, the ability of GBM cells to preserve EGFR overdosage in vitro
      remains controversial. Our experimental approach was based on quantitative
      analysis of EGFR gene dosage in vitro both at DNA and mRNA level. Real-time PCR
      data were verified with a FISH method allowing for a distinction between EGFR
      amplification and polysomy 7. We demonstrated that EGFR amplification accompanied
      by EGFRwt overexpression was maintained in spheroids, but these phenomena were
      gradually lost in adherent culture. We noticed a rapid decrease of EGFR
      overdosage already at the initial stage of cell culture establishment. In
      contrast to EGFR amplification, the maintenance of polysomy 7 resulted in EGFR
      locus gain and stabilization even in long-term adherent culture in serum
      presence. Surprisingly, the EGFRwt expression pattern did not reflect the latter
      phenomenon and we observed no overexpression of the tested gene. Moreover,
      quantitative analysis demonstrated that expression of the truncated variant of
      receptor-EGFRvIII was preserved in GBM-derived spheroids at a level comparable to
      the initial tumor tissue. Our findings are especially important in the light of
      research using glioblastoma culture as the experimental model for testing novel
      EGFR-targeted therapeutics in vitro, with special emphasis on the most common
      mutated form of receptor-EGFRvIII.

PMID- 20803306
TI  - Cytotoxic effects of statins and thiazolidinediones on meningioma cells.
AB  - Statins are inhibitors of the cholesterol synthesis pathway with pleiotropic
      effects, while thiazolidinediones (TDZ) are peroxisomal proliferator activator
      receptor gamma (PPAR-gamma) agonists with potent proapoptotic activity. For both
      groups of substances a cytotoxic effect against several human tumors is presumed.
      Direct comparison of several statins and TDZ has not been performed on meningioma
      cells until now. We compared the antiproliferative/cytotoxic effect of five
      statins, two TDZ, and their combinations on various human meningioma cell lines
      and nontumorous cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium
      bromide (MTT) assay, cell cycle analysis, and caspase-3 assay. Simvastatin (SMV)
      and its combination with the TDZ pioglitazone (PGZ) turned out to be the most
      effective treatment. After 96 h the 50% inhibition concentration (IC(50)) of SMV
      in MTT assays for two more sensitive meningioma cell lines (one benign and one
      malignant) was below 0.9 MUM, while the IC(50) was 2.8 MUM or higher for two
      other meningioma lines. Fluorescence-activated cell sorting (FACS) analysis
      suggested that MTT results mostly represented cytotoxic rather than
      antiproliferative effects. Strong caspase-3 induction suggested participation of
      intrinsic apoptosis in meningioma cell death. In contrast, SMV showed no
      substantial effects on fibroblasts and astrocytes. Addition of 40 MUM PGZ
      significantly decreased the fraction of clonogenic cells in soft-agar assays, as
      compared with 2.8 MUM SMV alone. Taken together, SMV showed a significant
      cytotoxic effect against human meningioma cells, which was moderately enhanced by
      PGZ.

PMID- 20803312
TI  - The woody plant poplar has a functionally conserved salt overly sensitive pathway
      in response to salinity stress.
AB  - In Arabidopsis thaliana, the salt overly sensitive (SOS) pathway plays an
      essential role in maintaining ion homeostasis and conferring salt tolerance. Here
      we identified three SOS components in the woody plant Populus trichocarpa,
      designated as PtSOS1, PtSOS2 and PtSOS3. These putative SOS genes exhibited an
      overlapping but distinct expression pattern in poplar plants and the transcript
      levels of SOS1 and SOS2 were responsive to salinity stress. In poplar mesophyll
      protoplasts, PtSOS1 was specifically localized in the plasma membrane, whereas
      PtSOS2 was distributed throughout the cell, and PtSOS3 was predominantly targeted
      to the plasma membrane. Heterologous expression of PtSOS1, PtSOS2 and PtSOS3
      could rescue salt-sensitive phenotypes of the corresponding Arabidopsis sos
      mutants, demonstrating that the Populus SOS proteins are functional homologues of
      their Arabidopsis counterpart. In addition, PtSOS3 interacted with, and recruited
      PtSOS2 to the plasma membrane in yeast and in planta. Reconstitution of poplar
      SOS pathway in yeast cells revealed that PtSOS2 and PtSOS3 acted coordinately to
      activate PtSOS1. Moreover, expression of the constitutively activated form of
      PtSOS2 partially complemented the sos3 mutant but not sos1, suggesting that
      PtSOS2 functions genetically downstream of SOS3 and upstream of SOS1. These
      results indicate a strong functional conservation of SOS pathway responsible for
      salt stress signaling from herbaceous to woody plants.

PMID- 20803313
TI  - Single-prolonged stress induces apoptosis by activating cytochrome C/caspase-9
      pathway in a rat model of post-traumatic stress disorder.
AB  - The purpose of this study was to provide a novel insight into the mechanism of
      how amygdala might participate in PTSD by investigating the changes of cytochrome
      c oxidase (COX), caspase-9, and caspase-3 in the amygdala of single-prolonged
      stress (SPS) rats. A total of 80 healthy, male Wistar rats were selected for this
      study. The models of post-traumatic stress disorder (PTSD) were created by SPS,
      which is an established animal model for PTSD. The change of COX was detected by
      light microscope and transmission electron microscopy (TEM). The expression of
      caspase-9 and caspase-3 in the basolateral amygdala was examined by
      immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR).
      SPS exposure resulted in a significant change of COX in the SPS model groups
      compared with the normal control group. Evaluation by enzymohistochemistry
      indicated translocation of COX from mitochondria to cytoplasm. The expression of
      both caspase-9 and caspase-3 significantly increased 1 day after SPS stimulation,
      then gradually increased and peaked at SPS 7d. This findings suggest changes of
      COX, caspase-9, and caspase-3 in the amygdala of SPS rats, which may play
      important roles in the pathogenesis of PTSD.

PMID- 20803314
TI  - A low concentration of atrazine does not influence the acute toxicity of the
      insecticide terbufos or its breakdown products to Chironomus tepperi.
AB  - The acute toxicities of the insecticide terbufos and its major breakdown products
      individually, as binary mixtures, and in combination with the co-applied
      herbicide atrazine were evaluated using final instar larvae of the midge
      Chironomus tepperi. Terbufos, terbufos sulfoxide and terbufos sulfone were highly
      toxic to C. tepperi with mean 96-h EC50 values of 2.13, 3.64 and 2.59 MUg/l,
      respectively. No interaction was observed between atrazine (25 MUg/l) and
      terbufos or its breakdown products while the binary mixture of terbufos sulfoxide
      and terbufos sulfone exhibited additive toxicity. The high toxicities of terbufos
      and its environmentally persistent oxidation products suggest that contamination
      of aquatic systems with this insecticide pose a threat to aquatic organisms
      whether or not atrazine is also present.

PMID- 20803315
TI  - Cardiovascular co-medication among users of antiobesity drugs: a population-based
      study.
AB  - AIM: The purpose of this study was to investigate to what extent patients using
      prescription antiobesity drugs (orlistat, sibutramine and rimonabant) used
      cardiovascular and antidiabetic drugs. An additional aim was to investigate
      whether such co-medication differed according to gender, age and amount of
      antiobesity drugs used. METHOD: Data were retrieved from the Norwegian
      Prescription Database (NorPD). All patients who had an antiobesity drug (ATC code
      A08A) dispensed from a Norwegian pharmacy between January 2004 and December 2007
      were included in the study. RESULTS: During the 4-year study period 83,717
      patients had antiobesity drugs dispensed. One in three patients using antiobesity
      drugs had at least on one occasion used a cardiovascular and/or an antidiabetic
      drug concomitantly. A significantly higher percentage of men used
      antihypertensives (40.4 vs. 27.2%, P < 0.0005), lipid modifying agents (24.4 vs.
      11.9%, P < 0.0005) and drugs used in diabetes (12.7 vs. 6.4%, P < 0.0005)
      concomitantly with antiobesity drugs when compared to women. The percentage of
      patients who had concomitant drug use increased markedly with age. One in four
      patients had antiobesity drugs dispensed only once during the period 2004-2007.
      CONCLUSION: Use of cardiovascular and antidiabetic drugs among patients using
      antiobesity drugs was extensive, especially among men and elderly patients.
      Overall, there was a high degree of polypharmacy among users of antiobesity
      drugs. Also, many patients dispensed antiobesity drugs in amounts that indicated
      use less than the recommended daily dose, and many dispensed antiobesity drugs
      only once. When prescribing antiobesity drugs to patients the potential benefits
      of antiobesity drugs should be considered in relation to the patients other
      chronic diseases and to the total complexity of the patients drug regimen.

PMID- 20803316
TI  - Association between drug prescribing and quality of life in primary care.
AB  - OBJECTIVE: To evaluate quality of life among patients of Family Health Strategy
      Units and how it relates to the prescribing complexity and to the number of
      psychotropic medications prescribed, including adjustments for sociodemographic
      characteristics. SETTING: Family Health Strategy Units in a municipality in the
      Brazilian state of Rio Grande do Sul. METHOD: Cross-sectional study using face-to
      face interviews and prescribing analysis among users of Family Health Strategy
      Units. Patients were recruited by consecutive sampling. Multiple linear
      regression models were fitted to the different domains of quality of life in the
      WHOQOL-Bref questionnaire. The response rate for the patients who completed the
      interview was 97%. The prescribed medication data and sociodemographic
      characteristics of the sample were included as covariates. Prescribing complexity
      was analyzed by means of the Medication Regimen Complexity Index. The assumptions
      in the estimated models were tested and the models were validated. MAIN OUTCOME
      MEASURE: Quality of life among patients of Family Health Strategy Units. RESULTS:
      At total, 336 patients answered the questionnaire. Through multiple linear
      regression, it was observed that higher prescribing complexity was associated
      with significantly low scores in the physical (-2.01, 95% CI = -2.89 to -1.35)
      and overall (-1.93, 95% CI = -2.81 to -0.99) quality of life domains. Greater
      amounts of psychotropic medications prescribed were associated with significantly
      low scores in the physical (-1.02, 95% CI = -1.29 to -0.56), psychological (
      2.52, 95% CI = -3.15 to -1.65) and overall (-0.97, 95% CI = -2.06 to -0.33)
      domains of the interviewees' quality of life. The estimated models were adjusted
      for the sociodemographic characteristics of the sample and presented good
      predictive capacity. CONCLUSIONS: The evaluated aspects of the prescribed
      medication (complexity and presence of psychotropic medications) were associated
      with low scores in the physical, psychological and overall quality of life
      domains. This may be an intrinsic characteristic of the interviewed patients,
      like having the quality of life at such a low level before starting the
      treatment, that the medication could not improve it to normal levels. Also, it
      can be a demonstration of the ineffectiveness of these treatments within primary
      health care.

PMID- 20803317
TI  - Validation of the medical outcomes study HIV (MOS-HIV) health survey among HIV
      infected patients in Taiwan.
AB  - OBJECTIVES: To examine both the reliability and the validity of the 'Medical
      Outcomes Study HIV' (MOS-HIV) health survey among HIV-infected patients in
      Taiwan. METHODS: Data were collected from 619 HIV-infected outpatients, with the
      reliability and the validity of the MOS-HIV survey subsequently being examined by
      multi-trait scaling techniques, internal consistency, convergent validity, known
      group validity and factorial validity. RESULTS: The MOS-HIV health survey was
      found to have excellent success rates in the item-consistency and discriminant
      validity tests, as well as good convergent validity and known-group validity. An
      acceptable fit was found for three of the four indices in the original two-factor
      model (non-normed fit index = 0.92, comparative fit index = 0.94 and standardized
      root mean squared residual = 0.056). CONCLUSIONS: The findings of the present
      study provide strong evidence in support of the reliability and validity of the
      MOS-HIV health survey for the assessment of quality of life among HIV-infected
      patients in Taiwan. We find that the original factor structure of the MOS-HIV
      survey remains valid for patients from Chinese cultural backgrounds. This study
      therefore contributes to the existing evidence within the extant literature on
      the cultural relevance of the MOS-HIV health survey (a measure originally
      developed within a Western culture) as a valid measure for cross-cultural
      comparative studies on health-related quality of life.

PMID- 20803318
TI  - National survey of the provision of day surgery across public and private
      hospitals in Ireland.
AB  - BACKGROUND: Day surgery (DS) is viewed as the optimal environment for many
      surgical procedures. Yet, Irish DS rates are low compared to international
      figures. AIMS: To describe the current provision of DS in Ireland and to identify
      barriers to its expansion. METHODS: Thirty-seven public hospitals and 17 private
      hospitals providing DS were surveyed during July/August 2009. RESULTS: Thirty
      seven hospitals replied (67%) (30 public, 7 private). DS beds ranged from 3 to
      39. Fourteen (38%) had dedicated DS units, and no unit had a consultant in
      charge. Twenty-one (57%) provided pre-assessment with 36 (96%) providing patient
      information leaflets both pre- and post-operatively. Stay-in rate was less than
      5%. Eight units had reviewed the adverse event rates following DS. Seven barriers
      to optimizing DS were identified, the main one being lack of dedicated DS
      theatres.

PMID- 20803319
TI  - Outside the high-volume unit: survival in an 11-year cohort of colorectal cancer
      patients.
AB  - INTRODUCTION: The policy of redistributing surgical case volume toward designated
      high-volume hospitals to improve outcome in cancer is supported by an
      international literature on volume-outcome association. METHODS: All patients who
      underwent surgery for colorectal carcinoma under the care of one surgeon at a non
      high-volume hospital 1995-2005 were identified. 5-year overall survival
      probability and 30-day operative mortality were measured. RESULTS: Two hundred
      and forty patients were identified. Mean annual surgeon caseload was 21.6 (SD
      4.2). 5-year overall survival probability was 57.1% (95% confidence interval +/
      7.4%). 30-day operative mortality was 4.6%. CONCLUSION: Estimates of outcome were
      not different from publically available values from a high-volume unit in
      Ireland. These findings suggest that concentrating case volume per se may not
      improve outcome to the extent desired. Future improvement in colorectal cancer
      outcome is just as likely to derive from wider screening, better surgical
      training, and adequately powered clinical research, should these accompany
      centralisation.

PMID- 20803320
TI  - Expression of RAD51, BRCA1 and P53 does not correlate with cellular
      radiosensitivity of normal human fibroblasts.
AB  - AIMS: To evaluate the potential role of key DNA repair proteins in the
      sensitivity of normal human fibroblasts to ionising radiations. METHODS:
      Radiosensitivity of six human fibroblast strains established from skin biopsies
      of women who had undergone conservative breast surgery and received a curative
      breast conserving radiotherapy was measured by colony-formation assay. The
      expression level of RAD51, BRCA1 and p53 proteins were studied using western blot
      analysis. RESULTS: The six fibroblast strains represent a typical spectrum of
      normal human radiosensitivity with the surviving fraction measured for a dose of
      3.5 Gy (SF3.5) ranging from 0.21 to 0.40. We found that these differences in cell
      survival did not correlate with the expression of RAD51, BRCA1 nor p53 in the
      tested normal human fibroblast strains. CONCLUSIONS: We conclude that measurement
      of protein expression of the three tested genes (RAD51, BRCA1 and p53) did not
      reflect sensitivity of normal fibroblasts to IR.

PMID- 20803324
TI  - Meeting report.

PMID- 20803323
TI  - Editorial.

PMID- 20803321
TI  - Drug treatment as HIV prevention: expanding treatment options.
AB  - Research conducted during the first 20 years of the AIDS epidemic provided a
      solid foundation of data supporting methadone treatment as HIV prevention. Drug
      users in methadone treatment were consistently found to reduce the frequency of
      drug use, risk behaviors, and infections. These data have been consistent over
      time and across cultural settings and have been used to promote the expansion of
      drug treatment as a prevention intervention. More recently, data have emerged
      suggesting the prevention potential of medication-assisted treatments other than
      methadone (buprenorphine/naloxone and naltrexone). Still, with a few notable
      exceptions, global drug treatment coverage for opiate injectors remains
      remarkably low and only a few treatment interventions for stimulant use have
      shown efficacy in reducing HIV risk. Importantly, more recent data provide
      support for the role of drug treatment programs in improving access and adherence
      to antiretroviral treatment and that injection drug users in substance abuse
      treatment are more likely to achieve sustained viral suppression. While important
      challenges remain in maximizing its impact, the scientific literature provides
      strong evidence of the efficacy of drug treatment as an HIV prevention strategy.

PMID- 20803325
TI  - Guest editorial.

PMID- 20803326
TI  - Implicit and explicit dosimetry in photodynamic therapy: a New paradigm.
AB  - Dosimetry for photodynamic therapy (PDT) is becoming increasingly complex as more
      factors are identified which may influence the effectiveness of a given
      treatment. The simple prescription of a PDT treatment in terms of the
      administered photosensitizer dose, the incident light and the drug-light time
      interval does not account for patient-to-patient variability in either the
      photosensitizer uptake, tissue optical properties or tissue oxygenation, nor for
      the interdependence of the photosensitizer-light-tissue factors. This
      interdependence is examined and the implications for developing adequate
      dosimetry for PDT are considered. The traditional dosimetric approach, measuring
      each dose factor independently, and termed here 'explicit dosimetry', may be
      contrasted with the recent trend to use photosensitizer photobleaching as an
      index of the effective delivered dose, termed here 'implicit dosimetry'. The
      advantages and limitations of each approach are discussed, and the need to
      understand the degree to which the photobleaching mechanism is linked, or
      'coupled', to the photosensitizing mechanism is analysed. Finally, the influence
      of the tissue-response endpoints on the optimal dosimetry methods is considered.

PMID- 20803327
TI  - Tumour visualization in a murine model by time-delayed fluorescence of
      sulphonated aluminium phthalocyanine.
AB  - Mice bearing the MS-2 fibrosarcoma were administered 0.25, 0.5 or 1 mg kg(-1)
      body weight (b.w.) of sulphonated aluminium phthalocyanine (AlS(2)Pc) (with
      average degree of sulphonation of 2.1), and time-gated fluorescence images were
      acquired up to 6 h after the injection. Different excitation wavelengths (610,
      650 and 670 nm) were tested. Red light excitation and 3 ns delayed detection
      allow one to minimize natural fluorescence and scattered laser light,
      respectively. The best conditions for tumour detection are reached under either
      650 or 670 nm Excitation, 2-4 h after the administration of either 0.5 or 1 mg
      kg(-1) b.w. of AlS(2)Pc. In these situations, the average fluorescence contrast
      between tumour area and surrounding healthy tissue is > 2, providing a clear
      identification of the pathological region. However, tumour localization is
      possible even after the injection of 0.25 mg kg(-1) b.w. of sensitizer. In
      conclusion, under low power excitation (< 100MuW cm(-2)), the technique allows
      real time detection of an intradermal tumour with good contrast.

PMID- 20803328
TI  - Endoscopic tissue characterization by frequency-domain fluorescence lifetime
      imaging (FD-FLIM).
AB  - Tissue characterization by endoscopic fluorescence imaging of endogenous or
      exogenous fluorochromes is a promising method for early cancer detection.
      However, the steady-state fluorescence contrast between healthy tissue and
      lesions such as early-stage carcinomas is generally poor. The authors propose to
      improve this contrast by using the additional information contained in the
      fluorescence lifetime (FLT). The FLT of several fluorochromes is sensitive to
      their physico-chemical environment.The FLT can be measured by frequency-domain
      methods. The excitation light from a continuous wave (CW) laser is modulated in
      amplitude at radio-frequencies by an electro-optic modulator, and delivered to
      the tissue via an optical fibre. The endoscopie site is imaged by an endoscope on
      to an optical device. The gain of the fluorescence image detector is also
      modulated at the same frequency for homodyning. The tissue fluorescence image is
      recorded at several phases between the excitation and the detection modulations
      during an acquisition cycle. With these images, an image processor calculates the
      apparent FLT for each pixel and constructs a lifetime image of the endoscopie
      site. This process is performed at quasi-video frequencies.The influence of
      various physical parameters (modulation frequency, number of images by cycle,
      shot noise, tissue optical properties etc.) has been investigated by analytical
      analysis, simulation methods and experimentation.Preliminary results obtained on
      human tissues are also presented to illustrate the potentiality of the method.

PMID- 20803329
TI  - Modulation of 5-ALA-induced PpIX xenofluorescence intensities of a murine tumour
      and non-tumour tissue cultivated on the chorio-allantoic membrane.
AB  - Exogenous administration of 5-aminolaevulinic acid (5-ALA), an early precursor in
      haem synthesis, induces accumulation of endogenous photo-active porphyrins,
      particularly protoporphyrin IX (PpIX). Modulation of 5-ALA-induced PpIX
      xenofluorescence intensities of a murine tumour and normal (non-tumour) tissue
      was studied in vivo on the chorio-allantoic membrane (CAM) of fertilized chicken
      embryos. Tumours were grown from the murine fibrosarcoma cell line SSK II. Murine
      3T3 fibroblasts (clone A31) were used for cultivating normal tissue. The
      autofluorescence and xenofluorescence intensities of 5-ALA-induced PpIX
      xenofluorescence were compared. After administration of 5-ALA to the CAM
      inoculated tissues, the SSK II tumours exhibited higher xenofluorescence
      intensities than the 3T3 tissues. Autofluorescence intensities of both types of
      tissue were not distinguishable. The effects of several biochemical reagents on
      the xenofluorescence intensities of the fibrosarcoma and fibroblast tissues were
      investigated. In both tissue types, the intensities increased after incubation
      with glucose and antimycin A, while nicotine-adenine-dinucleotide increased the
      3T3 fibroblast xenofluorescence more than the SSK II fibrosarcoma
      xenofluorescence. Incubation with dimethyl sulphoxide (DMSO) attenuated 5-ALA
      induced PpIX xenofluorescence, while oxamic acid attenuated the 3T3 fibroblast
      xenofluorescence more effectively than the xenofluorescence of SSK II
      fibrosarcoma. Ethanol and 2-iodoacetamide drastically decreased xenofluorescence
      intensities in both tumour and normal tissue.

PMID- 20803330
TI  - 5-aminolaevulinic-acid-induced formation of different porphyrins and their
      photomodifications.
AB  - The relative amounts of 5-aminolaevulinic acid (ALA)-induced hydrophobic and
      hydrophilic porphyrins produced in normal mouse tissue and solid Ehrlich ascites
      carcinoma in mice were investigated as a function of added glucose, light
      irradiation and restricted blood flow to the tumour. Protoporphyrin IX (PpIX) is
      the predominant porphyrin produced from exogenous ALA in tissues that have viable
      mitochondria. However, under special conditions which seem to be connected with a
      reduced viability of the mitochondria, the formation of water-soluble porphyrins
      can be observed in vivo. Fluorescence maxima of the water-soluble porphyrins are
      located in the region between 615 and 625 nm. Irradiation can further lead to the
      formation of PpIX photoproduct(s), showing a fluorescence emission band at 676
      nm. The photobleaching of PpIX in normal tissue and tumour tissue is different
      under restricted blood flow. ALA-induced PpIX can be observed in the normal blood
      stream, and can be linked to a slower photobleaching than in tissue with
      restricted blood flow.

PMID- 20803331
TI  - Temporal and illumination-induced variations in the in vivo light transmission
      spectra of four photosensitizers in EMT6/Ed murine tumours.
AB  - Temporal and illumination-induced variations in the in vivo light transmission
      spectrum of the photosensitizer will influence light dosimetry for photodynamic
      therapy (PDT). The present authors have studied the in vivo spectra of four
      photosensitizers in the EMT6/Ed murine tumour model in Balb/c mice. The following
      photosensitizers were used: bis(dimethylthexylsiloxy)silicon 2,3-naphthalocyanine
      (SiNc 8), benzoporphyrin-derivative monoacid ring A (BPD Verteporfin), Photofrin
      and ethanolamined hypocrellin B (HBEA-R2). Spectra were measured non-invasively
      in the EMT6/Ed murine tumour model in the spectral range 600-840 nm, using a
      diode laser, a dye laser and a Ti:sapphire laser. Red-shift and broadening of the
      SiNc 8 absorption band was observed at 790 nm, and a slight red-shift was
      observed in the BPD, HBEA-R2 and Photofrin in vivo absorption spectrum. Exposure
      to 300 J of light at the peak absorption wavelength caused complete
      photobleaching of BPD at 690 nm, and a reduced absorption by SiNc 8 at 780 nm,
      Photofrin at 626 nm, and HBEA-R2 at 656 nm.

PMID- 20803332
TI  - Tissue photosensitizer detection by low-power remittance fluorimetry.
AB  - A simple adaptation of a commercial spectrofluorimeter which allows the
      semiquantitative determination of photodynamic therapy photosensitizer
      fluorescence in accessible tissues is described. Light from a xenon lamp is
      directed via a monochromator onto the tissue surface by a bifurcated random fibre
      bundle. Tissue fluorescence is directed to the emission monochromator and
      photomultiplier of the fluorimeter by the second limb of the fibre bundle.
      Although relatively simple, this device can be used to carry out a wide range of
      useful measurements in clinical and experimental photodynamic therapy. The
      sensitivity and reproducibility of the measurements were determined using mouse
      tumour and muscle tissue fluorescence measured in vivo compared with
      photosensitizer content measured by high performance liquid chromatography. As an
      illustration of the potential applications of such systems, the time courses of
      fluorescence in the skin of patients treated with the photosensitizers
      Photofrin(R) and metatetra(hydroxyphenyl)chlorin (mTHPC) (temoporfin) and the
      photobleaching of 5-aminolaevulinic acid-derived protoporphyrin IX during
      treatment, are described.

PMID- 20803333
TI  - Applicator for light delivery and in situ light dosimetry during endobronchial
      photodynamic therapy: First measurements in humans.
AB  - This paper presents a design of an applicator for light delivery and light
      dosimetry during endobronchial photodynamic therapy (EB-PDT). The design
      incorporates a linear diffuser that is fixed in the centre of the lumen by a
      steel spring basket that does not block air flow. An isotropic light detector is
      included in this design, to measure the light fluence actually delivered to the
      bronchial mucosa surface. The applicator is designed for use with common
      bronchoscopy equipment, and can be used with bronchoscopes with a large biopsy
      channel ( approximately 3 mm). The first clinical measurements were performed and
      caused no additional discomfort to the (nonphotosensitized) patients. The data
      showed considerable inter-patient variability of the light fluence rate measured
      as a result of fixed output power of the diffuser. This fact and the expected
      strong dependence of the fluence rate on the lumen diameter stress the importance
      of in situ fluence rate measurement for a proper evaluation of the relationship
      between light fluence and the biological response of EB-PDT.

PMID- 20803334
TI  - A comparison of novel light sources for photodynamic therapy.
AB  - A diode laser, light-emitting diode (LED) array bandwidth 25 nm, full width half
      maximum (FWHM) and filtered arc lamp (bandwidth 40 nm, FWHM), all with peak
      emission at about 650 nm, suitable for the photosensitizer tetra(meta
      hydroxyphenyl)chlorin (mTHPC), were compared with a copper vapour laser pumped
      dye laser, using depth of necrosis in normal rat liver as a measure of
      photodynamic effect.A three-way comparison between a DL10K dye laser, the LED
      array and the filtered arc lamp resulted in mean depths of necrosis of 4.64, 4.29
      and 4.04 mm, respectively, at 20 J cm(-2), the values for the laser and arc lamp
      being significantly different at the 5% level. A further comparison of a narrower
      linewidth DL20K dye laser with the LED array, using a light dose of 20 J cm(-2),
      showed a significant difference between the mean depths of necrosis of 4.97 and
      4.05 mm, respectively (p=0.01).A final study, comparing the DL20K dye laser with
      the diode laser and a light dose of 10 J cm(-2), demonstrated no significant
      difference in depths of necrosis (3.23 and 3.25 mm, respectively). The results
      obtained in the three studies are attributed to the relative bandwidths of light
      emission for the various sources. A simple mathematical model is presented
      explaining the results in terms of the relative activation of the photosensitizer
      and the consequent threshold fluence required for the induction of necrosis.It is
      concluded that, in order to achieve the same depth of effect as a laser when
      using the broad band sources, the incident fluence would have to be approximately
      doubled. However, when the low cost and ease of use of the non-laser sources are
      taken into consideration, these devices are likely to find widespread
      applications in clinical photodynamic therapy.

PMID- 20803335
TI  - Wavelength-dependent effect of tetra(m-hydroxyphenyl)chlorin for photodynamic
      therapy in an 'early' squamous cell carcinoma model.
AB  - The purpose of the present study was to correlate the wavelength of the
      irradiation source with the phototoxic activity of tetra(m-hydroxyphenyl)chlorin
      (mTHPC) in healthy and neoplastic mucosae. The hamster tumour model for early
      squamous cell carcinoma was used in these experiments. In vitro and in vivo
      studies have shown that mTHPC absorbs significantly at 652 nm (1, 2). This
      wavelength is used currently in clinical mTHPC photodynamic therapy (PDT) trials.
      In order to study the wavelength dependence of the phototoxic effect on normal
      and tumour tissues, irradiation tests were performed 4 days after injection of
      0.5mg kg(-1) mTHPC. An argon-ion pumped dye laser was used as the light source.
      The light dose of 12 J cm(-2) was delivered at a light dose rate of 150 mW cm(
      2). The wavelength was varied between 642.5 and 665 nm at 2.5-nm increments. The
      PDT damage was evaluated in serial Haematoxylin and Eosin stained sections using
      a tissue-damage scale. Light between 647.5 and 652.5 nm induced the highest
      damage to both the healthy and tumour mucosae. At wavelengths equal to or below
      645 nm, and equal to or above 655 nm, tissue damage decreased. Wavelengths below
      642 nm and above 660 nm did not induce any visible tissue damage. These results
      suggest that the in vivo optimal wavelength range for PDT with mTHPC is between
      647 and 652 nm. This information is essential for selecting an appropriate light
      source.

PMID- 20803336
TI  - Differences in in vitro photodynamic sensitivity among head and neck cancers.
AB  - This study was conducted to address the question of how cancers of different
      histologies of the head and neck region responded to photodynamic therapy (PDT).
      Five human cancer cell lines were investigated: two squamous cell carcinoma lines
      (pharynx and tongue), mucoepidermoid carcinoma (submaxillary gland),
      rhabdomyosarcoma (embryonic) and adenocarcinoma (colon). The cell lines were
      treated with haematoporphyrin derivative (HpD) at doses of 0.78-25Mug ml(-1),
      with excitation of the absorbed drug by a 'black light' source (340-380 nm). An
      MTT assay demonstrated different PDT responses among the various cell types. On
      the basis of LD(50), the sensitivity of the different cell lines was ranked as
      follows: adenocarcinoma> squamous cell carcinoma> rhabdomyosarcoma>
      mucoepidermoid carcinoma. The magnitude of the LD(50) was suggested by a drug
      uptake study to be governed in part by cellular levels of sensitizer and in part
      by intrinsic cell sensitivity. This study provided information that may help to
      identify the histological types of head and neck cancers that would respond
      favourably to PDT.

PMID- 20803337
TI  - Basic research on the biology of meta-tetra(hydroxyphenyl) chlorin for
      photodynamic therapy in gynaecology: Somatic genotoxicity assayed withDrosophila
      melanogaster.
AB  - The well-established SMART test, a somatic mutation and recombination assay of
      Drosophila, was applied to assess the possible genotoxicity of sublethal meta
      tetra(hydroxyphenyl) chlorin (mTHPC) photodynamic therapy (PDT) to clonogenic
      cells in situ. The SMART assay monitors the loss of heterozygosity (LOH) at
      selected cell-marker loci in clonogenic cells of the larval wing primordia. No
      evidence of genotoxicity was observed under conditions that killed between 38 and
      86% of the exposed test larvae. Since the SMART assay is based on the oral uptake
      of the suspected genotoxic agent, the uptake kinetics of mTHPC by the assay's
      specific target cells must be known. Therefore, relevant studies are being
      carried out at present in order to draw final conclusions from this negative test
      result for genotoxicity.

PMID- 20803338
TI  - Lasers - a cutting edge in surgery.

PMID- 20803339
TI  - Ageing brain abnormalities in young obese patients with type 2 diabetes: a cause
      for concern.

PMID- 20803340
TI  - Fractionation and characterization of gold nanoparticles in aqueous solution:
      asymmetric-flow field flow fractionation with MALS, DLS, and UV-Vis detection.
AB  - Asymmetrical-flow field flow fractionation (AFFF) separates constituents based on
      hydrodynamic size and is emerging as a powerful tool for obtaining high
      resolution information on the size, molecular weight, composition, and stability
      of nanoscale particles in liquid media. We employ a customized AFFF system
      combining on-line detectors for multi-angle light scattering, dynamic light
      scattering, and UV-Vis absorption. Our objective is to develop optimized
      measurement protocols for the characterization of gold nanoparticles (GNPs),
      which are widely utilized in biomedical research and other nanotechnology
      applications. Experimental conditions have been optimized by controlling key
      parameters, including injection volume and solids concentration, mobile phase
      composition, membrane type and pore size, and ratio of channel-to-cross-flow
      rates. Individual citrate-stabilized GNP components (nominally 10, 20, 30, 40,
      and 60 nm) and GNPs functionalized with polyethylene glycol were separated from
      multicomponent GNP mixtures by AFFF and subsequently characterized. We discuss
      the effects due to variations in measurement parameters and GNP surface
      modification on observed retention, recovery, and peak resolution.

PMID- 20803341
TI  - Imaging characteristics of angiomatoid fibrous histiocytoma of bone.
AB  - We present the first report of a patient with angiomatoid fibrous histiocytoma of
      bone in the radiology literature. This tumor initially eluded diagnosis due to
      its similarities with chronic hematoma and aneurysmal bone cyst. Only two cases
      of angiomatoid fibrous histiocytoma have been reported in the radiology
      literature and both of these lesions were in the soft tissues. The fairly
      distinctive findings in our patient of multiple large cystic chambers with fluid
      fluid levels are similar to the findings in the two soft tissue case reports,
      suggesting that imaging may be used to suggest this specific diagnosis regardless
      of location, especially in the clinical setting of unexplained hematoma or
      anemia. Mention of this diagnosis in the radiology report may aid in the final
      diagnosis at pathology, because special techniques, including fluorescent in situ
      hybridization, must be applied in order to fully evaluate for the diagnosis.

PMID- 20803342
TI  - Delineation of upper urinary tract segments at MDCT urography in patients with
      extra-urinary mass lesions: retrospective comparison of standard and low-dose
      protocols for the excretory phase of imaging.
AB  - PURPOSE: Excretory-phase CT urography (CTU) may replace excretory urography in
      patients without urinary tumors. However, radiation exposure is a concern. We
      retrospectively compared upper urinary tract (UUT) delineation in low-dose and
      standard CTU. MATERIAL AND METHODS: CTU (1-2 phases, 120 KV, 4 * 2.5 mm, pitch
      0.875, i.v. non-ionic contrast media, iodine 36 g) was obtained with standard (14
      patients, n = 27 UUTs, average 175.6 mAs/slice, average delay 16.8 min) or low
      dose (26 patients, n = 86 UUTs, 29 mAs/slice, average delay 19.6 min) protocols.
      UUT was segmented into intrarenal collecting system (IRCS), upper, middle, and
      lower ureter (UU,MU,LU). Two independent readers (R1,R2) graded UUT segments as 1
      not delineated, 2-partially delineated, 3-completely delineated (noisy margins),
      4-completely delineated (clear margins). Chi-square statistics were calculated
      for partial versus complete delineation and complete delineation (clear margins),
      respectively. RESULTS: Complete delineation of UUT was similar in standard and
      low-dose CTU (R1, p > 0.15; R2, p > 0.2). IRCS, UU, and MU clearly delineated
      similarly often in standard and low-dose CTU (R1, p > 0.25; R2, p > 0.1). LU
      clearly delineated more often in standard protocols (R1, 18/6 standard, 38/31 low
      dose, p > 0.1; R2 18/6 standard, 21/48 low-dose, p < 0.05). CONCLUSIONS: Low-dose
      CTU sufficiently delineated course of UUT and may locate obstruction/dilation,
      but appears unlikely to find intraluminal LU lesions.

PMID- 20803343
TI  - Clustering of multifocal cerebral infarctions in CADASIL: a case report.

PMID- 20803344
TI  - Heterozygous X-linked adrenoleukodystrophy-associated myelopathy mimicking
      primary progressive multiple sclerosis.

PMID- 20803345
TI  - Anticipatory nausea and vomiting.
AB  - A commonly reported consequence of post-treatment nausea or vomiting is the
      development of anticipatory nausea and vomiting (ANV). In most published work,
      nausea is reported to occur before chemotherapy drugs are administered by
      approximately 20% of patients at any one chemotherapy cycle and by 25-30% of
      patients by their fourth chemotherapy cycle. Most studies in adult patients
      strongly support the view that the development of ANV involves elements of
      classical conditioning. The best method to avoid development of ANV is to
      adequately prevent both vomiting and nausea from the first exposure to
      chemotherapy. If anticipatory side effects develop, behavioral treatment
      techniques, such as systematic desensitization, have been shown effective.
      Benzodiazepines used in combination with behavioral techniques or antiemetics may
      also be useful. The evidence on which these conclusions are based is reviewed in
      this article.

PMID- 20803346
TI  - Catalytic performance and thermostability of chloroperoxidase in reverse micelle:
      achievement of a catalytically favorable enzyme conformation.
AB  - The catalytic performance of chloroperoxidase (CPO) in peroxidation of 2, 2'
      azinobis-(-3 ethylbenzothiazoline-6-sulfononic acid) diammonium salt (ABTS) and
      oxidation of indole in a reverse micelle composed of surfactant-water-isooctane
      pentanol was investigated and optimized in this work. Some positive results were
      obtained as follows: the peroxidation activity of CPO was enhanced 248% and 263%,
      while oxidation activity was enhanced 215% and 222% in cetyltrimethylammonium
      bromide (CTABr) reverse micelle medium and dodecyltrimethylammonium bromide
      (DTABr) medium, respectively. Thermostability was also greatly improved in
      reverse micelle: at 40  degrees C, CPO essentially lost all its activity after 5
      h incubation, while 58-76% catalytic activity was retained for both reactions in
      the two reverse micelle media. At 50  degrees C, about 44-75% catalytic activity
      remained for both reactions in reverse micelle after 2 h compared with no
      observed activity in pure buffer under the same conditions. The enhancement of
      CPO activity was dependent mainly on the surfactant concentration and structure,
      organic solvent ratio (V(pentanol)/V(isooctane)), and water content in the
      reverse micelle. The obtained kinetic parameters showed that the catalytic
      turnover frequency (k(cat)) was increased in reverse micelle. Moreover, the lower
      K(m) and higher k(cat)/K(m) demonstrated that both the affinity and specificity
      of CPO to substrates were improved in reverse micelle media. Fluorescence,
      circular dichroism (CD) and UV-vis spectra assays indicated that a catalytically
      favorable conformation of enzyme was achieved in reverse micelle, including the
      strengthening of the protein alpha-helix structure, and greater exposure of the
      heme prosthetic group for easy access of the substrate in bulk solution. These
      results are promising in view of the industrial applications of this versatile
      biological catalyst.

PMID- 20803347
TI  - Survival of commercial yeasts in the winery environment and their prevalence
      during spontaneous fermentations.
AB  - Inoculation of active dry yeasts during the wine-making process has become a
      common practice in most wine-producing regions; this practice may affect the
      diversity of the indigenous population of Saccharomyces cerevisiae in the winery.
      The aim of this work was to study the incidence of commercial yeasts in the
      experimental winery of Estacion de Viticultura e Enoloxia de Galicia (EVEGA) and
      their ability to lead spontaneous fermentations. To do this, 64 spontaneous
      fermentations were carried out in the experimental cellar of EVEGA over a period
      of 7 years. Samples were taken from must and at the beginning, vigorous and final
      stages of fermentation. A representative number of yeast colonies was isolated
      from each sample. S. cerevisiae strains were characterised by analysis of
      mitochondrial DNA restriction patterns. The results showed that although more
      than 40 different strains of S. cerevisiae were identified, only 10 were found as
      the dominant strain or in codominance with other strains in spontaneous
      fermentations. The genetic profiles (mtDNA-RFLPs) of eight of these strains were
      similar to those of different commercial yeasts that had been previously used in
      the EVEGA cellar. The remaining two strains were autochthonous ones that were
      able to reach implantation frequencies as high of those of commercial yeasts.
      These results clearly indicated that commercial wine yeasts were perfectly
      adapted to survive in EVEGA cellar conditions, and they successfully competed
      with the indigenous strains of S. cerevisiae, even during spontaneous
      fermentations. On the other hand, autochthonous dominant strains that presented
      desirable oenological traits could be of interest to preserve wine typicity.

PMID- 20803349
TI  - Divergent evolution of molecular markers during laboratory adaptation in
      Drosophila subobscura.
AB  - The impact of genetic drift in population divergence can be elucidated using
      replicated laboratory experiments. In the present study we used microsatellite
      loci to study the genetic variability and differentiation of laboratory
      populations of Drosophila subobscura derived from a common ancestral natural
      population after 49 generations in the laboratory. We found substantial genetic
      variability in all our populations. The high levels of genetic variability,
      similar across replicated populations, suggest that careful maintenance
      procedures can efficiently reduce the loss of genetic variability in captive
      populations undergoing adaptation, even without applying active management
      procedures with conservation purposes, in organisms that generate a high number
      of offspring such as Drosophila. Nevertheless, there was a significant genetic
      differentiation between replicated populations. This shows the importance of
      genetic drift, acting through changes in allele frequencies among populations,
      even when major changes in the degree of genetic diversity in each population are
      not involved.

PMID- 20803348
TI  - Evidence based on studies of the mus309 mutant, deficient in DNA double-strand
      break repair, that meiotic crossing over in Drosophila melanogaster is a two
      phase process.
AB  - The mus309 gene in Drosophila melanogaster encodes a RecQ helicase which is
      involved in DNA double-strand break (DSB) repair and specifically in the choice
      between the different pathways of the repair. In a brood pattern analysis of
      mus309 and wild type females which either had or had not experienced a
      temperature shock, different parameters of meiotic crossing over including map
      distances and crossover interference in the X chromosome were measured. The
      results suggest that, like in other eukaryotes studied, the control of meiotic
      crossover formation also in D. melanogaster is a two-phase process. The first
      phase seems to be temperature shock sensitive, independent of the mus309 gene and
      coincidental with the premeiotic DNA synthesis, thus most likely representing the
      formation of DSBs. The second phase seems to be temperature shock tolerant,
      dependent on the mus309 gene, occurring during the meiotic prophase and most
      likely representing the choice made by the oocyte between the different pathways
      of the DSB repair. A hypothesis of the localization of chiasmata is also
      presented, combining the mechanisms of interference and the so-called centromere
      effect, and based on the balance between the SDSA and DSBR pathways of DSB
      repair.

PMID- 20803350
TI  - Occurrence and financial loss assessment of cystic echinococcosis (hydatidosis)
      in cattle slaughtered at Wolayita Sodo municipal abattoir, Southern Ethiopia.
AB  - A cross-sectional study aimed at determining the prevalence and cyst
      characteristics and estimating the financial loss due to cystic echinococcosis
      (hydatidosis) in cattle slaughtered at Wolayita Sodo municipal abattoir was
      conducted from November 2009 to April 2010. Out of 546 cattle examined, 92
      (16.85%) were found to harbor visible hydatid cysts. Significantly higher
      infection was detected in local (P < 0.05) than crossbred cattle. No significant
      variation was observed with regard to origin, sex, and body condition status of
      animals. Regarding organ distribution, infections of the lung, liver, spleen, and
      kidney were 57.78%, 35.46%, 8.75%, and 4.01%, respectively. Of the total 1,097
      hydatid cysts counted, 952 (86.78%), 136 (12.4%), and eight (0.82%) were found to
      be small-sized, medium-sized, and large-sized, respectively. Likewise, out of 450
      cysts assessed, 138 (30.67%) were fertile, 241 (53.56%) sterile, and 71 (15.78%)
      calcified. Of the 138 fertile cysts subjected for viability test, 13 (9.42%) were
      viable while 125 (90.57%) were nonviable. Moreover, assessment of annual economic
      loss due to bovine hydatidosis at Wolayita Sodo municipal abattoir from offal
      condemnation and carcass weight loss was estimated at 410,755.90 Ethiopian Birr
      (ETB; 30,202.64 US$; 1 US$ = 13.60 ETB). Despite the moderate magnitude of
      infection detected currently, there seems to be an existing socioeconomic
      situation favorable for hydatidosis, and hence, it remains one of the most
      important diseases warranting serious attention for prevention and control
      actions in Wolayita zone. Hence, establishment of well-equipped standardized
      abattoirs, creation of public awareness, and control of stray dogs are of
      paramount importance.

PMID- 20803351
TI  - Incidence and significance of FLT3-ITD and NPM1 mutations in patients with normal
      karyotype acute myeloid leukaemia.
AB  - BACKGROUND: Acute myeloid leukaemia (AML) is a heterogeneous clonal disorder of
      haematopoietic progenitor cells. Approximately half of all adult AML patients
      have a normal karyotype (NK-AML) and an intermediate risk prognosis. AIMS: To
      determine the incidence and prognostic significance of NPM1 and FLT3-ITD
      mutations in a population of patients with NK-AML. METHODS: FLT3-ITD and NPM1
      mutation status was retrospectively sought in presentation samples from 44 NK-AML
      patients. RESULTS: FLT3-ITD and NPM1 mutations were detected in 45.5 and 54.5% of
      patients, respectively, allowing stratification according to genotype.
      CONCLUSIONS: FLT3-ITD and NPM1 mutation status can be defined in NK-AML.
      Prospective screening for these mutations is advocated in all NK-AML patients, as
      the genotype is of clinical importance when considering treatment options
      including stem cell transplantation.

PMID- 20803352
TI  - Follicular lymphoma prognostic factors in the modern era: what is clinically
      meaningful?
AB  - Follicular lymphomas (FL) account for 30% of non-Hodgkin's lymphomas (NHL). Their
      evolution is heterogeneous. Some patients present with indolent forms undergoing
      several relapses while in other patients the disease evolves abruptly toward
      aggressive NHL. This is why accurate prognostic indices are required so that
      treatment strategies may be optimized for each patient and so that trials may be
      conducted in groups of patients that are as homogeneous as possible. The
      Follicular Lymphoma International Prognostic Index (FLIPI) has been designed to
      separate patients into 3 groups with significantly different hazard ratios for
      death. Its accuracy has been confirmed in several studies. The FLIPI2 was
      designed more recently to separate patients with significantly different hazard
      ratios for progression/relapse in the era of anti-CD20 monoclonal antibody
      treatments. Gene profile studies have shown that the prognosis of FL is mainly
      related to the type, number, and activation of immune cells in the
      microenvironment of lymphomatous follicles. Immunohistochemical studies suggest
      that macrophages, CD4+ T cells and among them T-regulatory cells (T-regs) and
      programed death-1 cells (PD-1 cells) play a major role in the outcome of FLs.
      However, additional confirmatory studies are required due to discrepancies in
      results. Up to now, these biological study results are more useful for
      approaching the pathophysiology of FL rather than to be used as prognostic tools
      in clinical practice.

PMID- 20803354
TI  - Systematic review of patellar resurfacing in total knee arthroplasty.
AB  - Controversies existing over resurfacing the patella in total knee arthroplasty
      remain in the literature. The purpose of this review was to evaluate the
      effectiveness of resurfacing versus nonresurfacing the patella in total knee
      arthroplasty. We searched the Cochrane Library, MEDLINE and EMBASE for published
      randomised clinical trials relevant to patellar resurfacing. The relative risk of
      reoperation was significantly lower for the patellar resurfacing group than for
      the nonresurfacing group (relative risk 0.57, 95% confidence interval 0.38-0.84,
      P =0.004). The overall incidence of postoperative anterior knee pain of the 1,421
      knees included was 12.9% in the patellar resurfacing group and 24.1% in the
      nonresurfacing group. The existing evidence indicates that patellar resurfacing
      can reduce the risk of reoperation with no improvement in postoperative knee
      function or patient satisfaction over total knee arthroplasty without patellar
      resurfacing. Whether it can decrease the incidence of anterior knee pain remains
      uncertain.

PMID- 20803353
TI  - Heat shock proteins as biomarkers for the rapid detection of brain and spinal
      cord ischemia: a review and comparison to other methods of detection in thoracic
      aneurysm repair.
AB  - The heat shock proteins (HSPs) are members of highly conserved families of
      molecular chaperones that have multiple roles in vivo. We discuss the HSPs in
      general, and Hsp70 and Hsp27 in particular, and their rapid induction by severe
      stress in the context of tissue and organ expression in physiology and disease.
      We describe the current state of knowledge of the relationship and interactions
      between extra- and intracellular HSPs and describe mechanisms and significance of
      extracellular expression of HSPs. We focus on the role of the heat shock proteins
      as biomarkers of central nervous system (CNS) ischemia and other severe stressors
      and discuss recent and novel technologies for rapid measurement of proteins in
      vivo and ex vivo. The HSPs are compared to other proposed small molecule
      biomarkers for detection of CNS injury and to other methods of detecting brain
      and spinal cord ischemia in real time. While other biomarkers may be of use in
      prognosis and in design of appropriate therapies, none appears to be as rapid as
      the HSPs; therefore, no other measurement appears to be of use in the immediate
      detection of ongoing severe ischemia with the intention to immediately intervene
      to reduce the severity or risk of permanent damage.

PMID- 20803356
TI  - Assessment of the effect of rapid crystalloid infusion on stroke volume variation
      and pleth variability index after a preoperative fast.
AB  - OBJECTIVE: Stroke volume variation (SVV) during controlled mechanical ventilation
      is a useful predictor in response to volume expansion, and pleth variability
      index (PVI), a novel algorithm allowing for automated and continuous calculation
      of the respiratory variations in the pulse oximeter waveform amplitude, can also
      predict fluid responsiveness non-invasively in mechanically ventilated patients.
      The aim of this study was (1) to determine whether acute fluid infusion affects
      SVV and PVI, and (2) to compare the two values in the case of acute fluid
      infusion after a preoperative fast following general anesthesia induction.
      METHODS: After tracheal intubation, the patients' lungs were mechanically
      ventilated. Subjects were anesthetized using sevoflurane and were given a rapid,
      constant-rate infusion of crystalloid (500 ml in 15 min). Systolic arterial
      pressure (SAP), diastolic arterial pressure (DAP), heart rate (HR), cardiac
      output (CO), cardiac index (CI), SVV, and PVI were measured at baseline and after
      250 and 500 ml had been infused, and these values were compared. RESULTS: SAP,
      DAP, CO, and CI were unchanged after the infusion. HR and SVV decreased
      significantly after the infusion. SVI increased significantly after the infusion.
      There was a significant difference in PVI only between the post 250 ml and post
      500 ml infusions. CONCLUSIONS: A rapid infusion of 250-500 ml of a crystalloid in
      nearly healthy subjects who had fasted overnight returned their SVV to within the
      normal range. In such cases, SVV is a more sensitive predictor of fluid
      responsiveness than is PVI, and the infusion gradually increased SVI.

PMID- 20803357
TI  - Emerging therapies for heart failure: renal mechanisms and effects.
AB  - Improved understanding of the pathophysiology of salt and water homeostasis has
      provided a foundation for explaining the renal mechanisms of emerging therapies
      for heart failure, as well as why renal function might potentially be improved or
      harmed. These aspects are reviewed in this article for a number of newer
      therapies including adenosine, endothelin, and vasopressin receptor antagonists,
      as well as extracorporeal ultrafiltration. An appreciation of the complexity and
      sometimes opposing pathways of these approaches may explain their limited
      efficacy in early trials, in which there has not been a substantial improvement
      in patient or renal outcomes. In that there is often a balance between beneficial
      and maladaptive receptor actions and neurohumoral responses, this physiologic
      approach also provides insight into the rationale for combining therapies. Multi
      agent strategies may thus maximize their effectiveness while minimizing adverse
      effects and tolerance. In this paper, the theoretical impact of the emerging
      agents based on their mechanism of action and pathophysiology of the disease is
      initially addressed. Then, the available clinical evidence for each class of
      drugs is reviewed with special emphasis on their effect on kidney-related
      parameters. Finally, a general overview of the complexity of the interpretation
      of trials is offered along with a number of potential explanations for the
      observed results.

PMID- 20803359
TI  - Risk factors for seizures in ischemic stroke: mainly cortical involvement?

PMID- 20803360
TI  - Social cognition in schizophrenia: cognitive and affective factors.
AB  - INTRODUCTION: Social cognition refers to how people conceive, perceive, and draw
      inferences about mental and emotional states of others in the social world.
      Previous studies suggest that the concept of social cognition involves several
      abilities, including those related to affect and cognition. The present study
      analyses the deficits of individuals with schizophrenia in two areas of social
      cognition: Theory of Mind (ToM) and emotion recognition and processing. Examining
      the impairment of these abilities in patients with schizophrenia has the
      potential to elucidate the neurophysiological regions involved in social
      cognition and may also have the potential to aid rehabilitation. METHODS: Two
      experiments were conducted. Both included the same five tasks: first- and second
      level false-belief ToM tasks, emotion inferencing, understanding of irony, and
      matrix reasoning (a WAIS-R subtest). The matrix reasoning task was administered
      to evaluate and control for the association of the other tasks with analytic
      reasoning skills. Experiment 1 involved factor analysis of the task performance
      of 75 healthy participants. Experiment 2 compared 30 patients with schizophrenia
      to an equal number of matched controls. Results. (1) The five tasks were clearly
      divided into two factors corresponding to the two areas of social cognition, ToM
      and emotion recognition and processing. (2) Schizophrenics' performance was
      impaired on all tasks, particularly on those loading heavily on the analytic
      component (matrix reasoning and second-order ToM). (3) Matrix reasoning, second
      level ToM (ToM2), and irony were found to distinguish patients from controls,
      even when all other tasks that revealed significant impairment in the patients'
      performance were taken into account. CONCLUSIONS: The two areas of social
      cognition examined are related to distinct factors. The mechanism for answering
      ToM questions (especially ToM2) depends on analytic reasoning capabilities, but
      the difficulties they present to individuals with schizophrenia are due to other
      components as well. The impairment in social cognition in schizophrenia stems
      from deficiencies in several mechanisms, including the ability to think
      analytically and to process emotion information and cues.

PMID- 20803358
TI  - Obstetrical and neonatal outcomes of pregnancies following gastric bypass
      surgery: a retrospective cohort study in a French referral centre.
AB  - BACKGROUND: The objective of this study was to analyze obstetrical and neonatal
      outcomes following Roux en Y Gastric Bypass procedures (RYGBP). METHODS: A
      retrospective cohort study was conducted in a single French tertiary perinatal
      care and bariatric center. The study involved 24 pregnancies, following RYGBP
      (exposed group) and two different control groups (non-exposed groups). A body
      mass index (BMI)-matched control group included 120 pregnancies matched for age,
      parity, and pregnancy BMI. A normal BMI control group included 120 pregnancies
      with normal BMI (18.5-24.9 kg/m(2)), matched for age and parity. Hospital data
      were reviewed from all groups in the same 6-year period. Obstetrical and neonatal
      outcomes after RYGB were compared, separately, to the two different-matched
      control groups. RESULTS: The median interval from RYGBP to conception was 26.6
      (range: 3-74) months. Rates of perinatal complications did not differ
      significantly between the RYGBP group and normal BMI and BMI-matched controls
      groups. The rate of Cesarean section before labor was higher in the RYGBP
      patients than in the normal BMI control group (25% vs. 9.3% respectively, p =
      0.04). Weight gain was lower in the RYGBP patients than normal BMI control group
      (5.8 kg vs. 13.2 kg respectively, p < 0.0001). Birthweight was also lower in the
      RYGBP group than those in normal BMI and BMI-matched controls groups (2,948.2 g
      vs. 3,368.2 g and 3,441.8 g, respectively, p < 0.0001). CONCLUSIONS: RYGBP
      surgery was associated with reduced birthweight, suggesting a possible role of
      nutritional growth restriction in pregnancy.

PMID- 20803361
TI  - Organophosphorus pesticide residues in raw milk and infant formulas from Spanish
      northwest.
AB  - Residue levels of seven organophosphorus pesticides (OPPs), widely used as dairy
      cattle ectoparasiticides or in crops used for animal feed, were determined in raw
      milk and infant formulas. A total of 312 samples were collected (70 from infant
      formulas and 242 from raw milk) biweekly during a 24-month period. Pesticides
      were extracted by means of a solid phase system into acetone. An extract aliquot
      of acetone was injected into a gas chromatograph (GC) with a nitrogen-phosphorus
      detector. Recoveries of pesticides spiked in milk samples were 62.2 - 97.2 %. The
      frequency of total samples containing detectable levels of OPP residues was 6.73
      % in total milk and 8.67 % in raw milk. The highest percentage incidence measured
      was for dichlorvos (5.78 %), followed by coumaphos (2.06 %), and parathion methyl
      (0.83 %). The range of positive results was calculated to be between 0.005 and
      0.220 mg kg(- 1). No residue was detected in the final product (infant formulas),
      so any risk to consumer health, especially to children's health, would be
      limited.

PMID- 20803362
TI  - Study on acute toxicity and structure-activity relationship of zebrafish (Danio
      rerio) exposed to naphthoquinones.
AB  - In this paper, we evaluated the acute toxicity of five naphthoquinone compounds,
      expressed as median lethal concentration at 96 h (LC(50)) using zebrafish as a
      model. The five compounds were classified as harmful or very toxic. The Gaussian
      method was used to calculate the quantitative-chemical parameters of each
      compound. Based on the structure-activity relationship analysis, the interaction
      between the naphthoquinones and the target is likely mediated by 1-carbonyl and
      the hydrophobic fraction substituted in alpha -position of naphthoquinone via
      hydrogen bonding and hydrophobic interactions. Our results provide a foundation
      for evaluating the aquatic ecological risk and the mode of action of
      naphthoquinones in the environment.

PMID- 20803363
TI  - Micronucleus frequency in sheep lymphocytes after in vitro exposure to fungicide
      tolylfluanid.
AB  - The fungicide tolylfluanid (N -dichlorofluoromethylthio-N', N -dimethyl -N -p 
      tolylsulfamide), was investigated by cytokinesis-block micronucleus assay.
      Tolylfluanid at the lowest concentration (1 x 10(- 6)mol L(- 1))did not influence
      significantly the frequency of micronuclei in sheep lymphocyte cultures in
      comparison with control (32.33 +/- 3.51/1000 binucleated cells versus 30.33 +/-
      2.82/1000 binucleated cells in dimethylsulfoxide (DMSO) control, P = 0.44).
      Higher tolylfluanid concentrations (1 x 10(- 4) and, 1 x 10(- 5) mol L(- 1))
      resulted in a significant dose-dependent increase in the number of micronuclei in
      comparison with control (74.00 +/- 13.00/1000 binucleated cells and 52.67 +/-
      10.12/1000 binucleated cells versus 30.33 +/- 2. 82/1000 binucleated cells in
      DMSO control, P = 0.005 and 0.02, respectively, ANOVA followed by Tukey test P <
      0.05). Many of the treated cells also possessed multiple micronuclei.
      Tolylfluanid did not affect the nuclear division index at all treatment
      concentrations. Our in vitro results thus demonstrate that tolylfluanid had a
      significant genotoxic effect at only the highest concentration tested.

PMID- 20803364
TI  - Development of an efficient extraction method for oxytetracycline in animal
      manure for high performance liquid chromatography analysis.
AB  - Oxytetracycline (2-(amino-hydroxy-methylidene)-4-dimethylamino-5,6,10,11,12a
      pentahydroxy-6-methyl-4,4a,5,5a-tetrahydrotetracene-1,3,12-trione) is a major
      member of the tetracycline antibiotics family of which are widely administered to
      animals in concentrated animal feeding operations for purposes of therapeutical
      treatment and health protection. With the disposal of animal manure as fertilizer
      into agricultural land, tetracyclines enter the environment. However,
      tetracyclines chelate with multivalent cations and proteins, resulting in low
      extraction efficiencies from animal manure for tetracycline residue analysis. In
      this study an efficient extraction method for oxytetracycline from steer manure
      using methanol/water solution amended with chelating organic acid was developed
      for the analysis of high performance liquid chromatography. The effect of species
      and amount of amendment acids, shaking time, methanol/water ratio, manure weight,
      and repeated times of extraction was investigated. It was optimized to amend 2.5
      g citric acid and 1.1 g oxalic acid with 10.0 g manure sample in a 50-ml
      centrifuge tube and extract with 15 ml methanol/water (9:1 in volume) by
      vigorously shaking for 30 min in a reciprocating shaker. After centrifugation at
      11,000 rpm, supernatant is collected. Sample was extracted for a total of 3
      times. The developed extraction method was further applied to extract
      oxytetracycline from fresh and aged cow manure, swine and poultry manure, and
      soil. Satisfactory recoveries ranging from (84.1 +/- 2.4) % to (102.0 +/- 3.1) %
      were obtained, demonstrating that the optimized extraction method is robust for
      oxytetracycline from different manure sample matrixes.

PMID- 20803365
TI  - The effect of fluorescent tracers on droplet spectrum, viscosity, and density of
      pesticide formulations.
AB  - The most important factor affecting efficacy and drift of pesticide applications
      is the droplet spectrum. To measure pesticide drift, researchers utilize
      fluorescent tracers to rapidly quantify spray deposition. Although fluorescent
      tracers have been used for more than 50 years, no experiments have been performed
      on the effect they have on the properties of pesticide formulations (density and
      viscosity) or droplet spectrum, which affect the drift of pesticides. Therefore,
      we examined the effect of an oil- and water-based tracer on the volume median
      diameter (VMD), viscosity, and density of oil- and water-based pesticide
      formulations. In addition, we experimentally fit and demonstrate the utility of
      using distributions to characterize pesticide droplet spectra. The addition of
      tracers to both water- and oil-based formulations did not significantly alter the
      VMD, viscosity, and density. Lognormal distributions provided the best fit for
      the water- and oil-based formulations with and without tracer. Our results
      demonstrated that the addition of oil- and water-based tracers do not
      significantly alter pesticide formulations properties and droplet spectrum, and
      most likely do not alter the movement of pesticide droplets in the environment.

PMID- 20803366
TI  - Headspace solid phase microextraction method for determination of triazine and
      organophosphorus pesticides in soil.
AB  - A headspace solid phase microextraction method (HS-SPME) for simultaneous
      determination of five pesticides belonging to triazine and organophosphorus
      pesticide groups in soil samples was developed. Microextraction conditions, such
      as temperature, extraction time and sodium chloride (NaCl) content were
      investigated and optimized using 100 microm polydimethyl-siloxane (PDMS) fiber.
      Detection and quantification were done by gas chromatography-mass spectrometry
      (GC-MS). Relative standard deviation (RSD) and recovery values for multiple
      analysis of soil samples fortified at 30 microg kg(- 1) of each pesticide were
      below 13 % and higher than 70 %, respectively. Limits of detection (LOD) for all
      the compounds studied were less than 3.2 microg kg(- 1). The proposed method was
      applied in the analysis of some agricultural soil samples.

PMID- 20803367
TI  - The effects of high metal concentrations in soil-compost mixtures on soil
      enzymes.
AB  - The study was undertaken to determine the impact of high-metal composts on the
      activities of four soil enzymes. High concentrations of metal salts (Cr, Cu, Ni
      or a Co-Mo-Pb combination) were added to feedstocks during the thermophilic stage
      of composting. These four metal-enriched composts and an unamended control
      compost were then mixed with soil collected from long-term agriculture plots
      under organic management or conventional management. The compost-soil mixtures
      were prepared at two rates (1:1 or 1:3 compost:soil, v/v) and incubated at 20
      degrees C for three weeks. These 20 combinations plus the five composts and the
      two soils were added to pots and incubated for three weeks. Following incubation,
      soil enzyme activities (acid phosphatase, arysulfatase, dehydrogenase,
      phosphodiesterase) were measured using traditional assay procedures. Compared to
      the control, none of the high-metal composts inhibited soil enzyme activity.
      Notably, the Cu compost treatment produced significantly higher activity of all
      four enzymes in the soil compared to the control. Previous soil management
      influenced the activity of three enzymes, arysulfatase and dehydrogenase had
      greater activity in the organic soil while phosphatase activity was greater in
      the conventional soil. Increasing the proportion of compost in the pot had a
      positive effect on phosphodiesterase activity only. In conclusion, the high-metal
      compost treatments either enhanced or caused no adverse effects on soil enzyme
      activity.

PMID- 20803369
TI  - Mapping particulate matter at the body weld department in an automobile assembly
      plant.
AB  - A respiratory health survey conducted in an assembly plant in 2000-2001 found
      that welders had elevated rates of self-reported respiratory symptoms compared
      with painters and assembly workers. Subsequently, the ventilation system was
      improved at the body weld department. In a follow-up study, particle spatial
      distributions were analyzed, following a mapping protocol developed specifically
      for this workplace, to evaluate the effectiveness of the changes. Significant
      temporal and spatial variations were observed. Temporal variation during a shift
      was monitored with over-shift stationary sampling at fixed locations. Spatial
      variation was evaluated with 1-min time-weighted average particle concentrations
      measured throughout the process areas (212 locations). The arithmetic spatial
      mean across 212 locations for the respirable particles varied from 305
      microg/m(3) to 501 microg/m(3) on 6 sampled days, with a standard deviation of 71
      microg/m(3), indicating that the difference between before and after
      countermeasures must be at least 191 microg/m(3) to be considered statistically
      significant at the given sample sizes. The available data were not sufficient to
      evaluate the reduction of the particle concentrations after the countermeasures.
      The map of particle mass concentration revealed several high concentration areas,
      requiring further investigation and potentially higher level of controls.
      Resistance welding needed to be effectively controlled, as it could be the major
      particle emitting sources in the facility. The map of submicrometer (0.014 microm
      to 1.0 microm) particle count concentration presented different patterns from
      that of respirable particle mass concentration, indicating that the submicrometer
      particles tended to be more evenly distributed over the process areas. Workers
      not in proximity to intensive welding operations might be exposed to fine
      particles at levels higher than had traditionally been thought. Mapping was
      demonstrated to be an effective method to assess particle spatial distributions.
      A well-designed sampling protocol is critical to achieving the specific aims of a
      mapping study.

PMID- 20803371
TI  - Life scripts for emotionally charged autobiographical memories: A cultural
      explanation of the reminiscence bump.
AB  - Two studies examined the ability of the life script account to explain the
      reminiscence bump for emotionally charged autobiographical memories among
      Malaysian participants. In Study 1 volunteers, aged 50-90 years, participated in
      a two-phased task. In the first phase, participants estimated the timing of 11
      life events (both positive and negative) that may occur in a prototypical life
      course within their own culture. Two weeks later the participants retrieved the
      same set of events from their lives and reported how old they were when those
      events occurred. In the second study 92 undergraduate students produced life
      scripts for the same 11 events. The findings revealed reminiscence bumps in both
      life script and retrieval curves for the memories judged happiest, most
      important, most in love, and most jealous. A reminiscence bump was also noted for
      success, although this was later in the lifespan than other reminiscence bumps.
      It was suggested that the life scripts can be used as an alternative account for
      the reminiscence bump, for highly positive and occasionally for negative
      autobiographical memories.

PMID- 20803372
TI  - Essential oil compositions of different accessions of Coriandrum sativum L. from
      Iran.
AB  - Coriander (Coriandrum sativum L.) has been cultivated for a many years in
      different parts of Iran. The chemical profiles of different accessions were
      analysed by means of GC-MS. The essential oil content of the dried seeds varied
      from 0.1% to 0.36%. Thirty-four different compounds were identified in the
      essential oil of all accessions. Linalool (40.9-79.9%), neryl acetate (2.3
      14.2%), gamma-terpinene (0.1-13.6%) and alpha-pinene (1.2-7.1%) were identified
      as main components in the oil of the coriander accessions. Almost all of the
      studied accessions contained more that 60% linalool, showing the high quality of
      coriander seeds produced in Iran and the suitability of the accessions as initial
      genetic materials for the breeding of homogenous and talented Coriander
      cultivars.

PMID- 20803373
TI  - Studies on the phenolic profiling, anti-oxidant and cytotoxic activity of Indian
      honey: in vitro evaluation.
AB  - Commercial honey types were screened for phenolic profile and anti-oxidant
      capacity. Phenolic profiling was done using high performance liquid
      chromatography, which was further corroborated with electro spray ionisation-mass
      spectroscopy. Dihydroxy benzoic acid, caffeic acid, ferulic acid and cinnamic
      acid were the major phenolic constituents found in the honey samples. The anti
      oxidant content and free-radical scavenging effect of honey were established
      using various assays. Total anti-oxidant potential and free-radical scavenging
      ability varied among the honey varieties and exhibited significant correlation
      with their phenolic content. Further, honey samples with richly abundant phenolic
      content were found to limit oxidant-induced cell death more effectively.
      Cytotoxic studies of a selected sample on a breast cancer cell displayed growth
      inhibition, depending on the concentration used. Cell cycle analysis indicated
      increasing accumulation of cells at the sub-G(1) phase. These results summarise
      the phenolic profile and anti-oxidant and cytotoxic potential of Indian honey
      samples for the first time.

PMID- 20803374
TI  - A new triterpenoid saponin from the aerial parts of Cephalaria ambrosioides.
AB  - A new allose-containing triterpenoid saponin (1), along with a known saponin (2),
      were isolated from the aerial parts of Cephalaria ambrosioides. Their structures
      were determined by spectroscopic (2D-NMR and ESI-MS) methods. The preferred
      conformation of 1 was determined by the NOESY spectrum.

PMID- 20803375
TI  - Determination of the n-alkane profile of epicuticular wax extracted from mature
      leaves of Cestrum nocturnum (Solanaceae: Solanales).
AB  - An n-hexane extract of fresh, mature leaves of Cestrum nocturnum (Solanales:
      Solanaceae) containing thin layer epicuticular waxes was analysed by thin-layer
      chromatography, infrared and gas liquid chromatography using standard
      hydrocarbons. Seventeen long chain alkanes (n-C(18) to n-C(34)) were identified
      and quantified. Hentriacontane (n-C(31)) was established as the major n-alkane,
      while nonadecane (n-C(19)) was the least abundant component of the extracted wax
      fraction. The carbon preference index calculated for the sample was 1.30, showing
      an odd to even carbon number predominance.

PMID- 20803376
TI  - Contaminations of herbal products determined by NMR fingerprint.
AB  - The utilisation of NMR fingerprinting is proposed as a rapid, available and
      reliable method to determine the contamination of herbal products. The presence
      of nimesulide has been reported recently as the contaminant of P.C. 28 Plus, a
      product based on herbal drugs marketed by the Italian company Cosval. The
      presence of the substance, as well as its relevant concentration (5%), was first
      reported by HPLC/MS analysis by other authors. The use of an NMR fingerprint
      confirmed the previous contamination with nimesulide in P.C. 28 Plus. The same
      contaminant was also found in P.C. 28 Pink. Furthermore, an analysis of Alergix
      Plus, another product of the same factory, evidenced the presence of bromhexin.

PMID- 20803377
TI  - Composition of volatile organic compounds in flowers of Astragalus sahendi.
AB  - A hydrodistillation sampling method, coupled to gas chromatography-mass
      spectrometry, was used in monitoring the volatile organic compounds in flowers of
      Astragalus sahendi. Accordingly, a total of 48 compounds were recognised, which
      were united by their terpenoid or aliphatic skeletons and low molecular weight.
      Above all, the significant presence of some insect-favoured terpenoid compounds,
      such as farnesol, cis- and trans-geraniol, alpha-bisabolol, nerolidol isomer,
      alpha-terpineol, alpha-terpinolene and thymol was significant. These findings
      confer a better understanding of pollination processes in the giant genus
      Astragalus. Furthermore, the results add to an increasing quantity of data
      corroborating the ecologic and evolutionary correlation between the floral
      bioactive compounds of plant species and their special types of pollinators.

PMID- 20803378
TI  - Structural elucidations and spectral assigments of two novel triterpene
      glycosides from Cephalaria paphlagonica.
AB  - Two novel triterpene glycosides, paphlagonoside A (1) and B (2), were
      characterised as 28-O-[beta-D-glucopyranosyl(1 --> 2)-alpha-L-arabinopyranosyl(1 
      -> 4)-beta-D-glucopyranosyl]-hederagenin (1) and 28-O-[beta-D-xylopyranosyl(1 -->
      4)-alpha-L-rhamnopyranosyl(1 --> 3)-beta-D-xylopyranosyl (1 --> 6)-beta-D
      glucopyranosyl(1 --> 2)-beta-D-glucopyranosyl]-hederagenin (2) from Cephalaria
      paphlagonica (Dipsacaceae). In addition to these, a common natural product
      (hederagenin) (3) was also isolated. The structures of all compounds were
      identified by spectroscopic and chemical methods. The antimicrobial and
      antioxidant activities of the plant extracts were examined by MIC and DPPH
      activity methods, respectively.

PMID- 20803379
TI  - Essential oils from stem and leaves of Angelica urumiensis (Mozaffarian) from
      Iran.
AB  - The composition of essential oils of the leaves and stem of Angelica urumiensis
      were analysed by chromatography-mass spectrometry. Overall, 58 volatile
      components were identified on the basis of their mass spectra characteristics and
      retention indices. Twenty-seven compounds were identified in the oil of the
      leaves, comprising 94.69% of the total oil, in which alpha-cadinol (20.2%),
      palmitic acid (14.14%), hexahydrofarnesyl acetone (10.03%), 1-dodecanol (7.55%),
      linoleic acid (6.37%) and oleic acid (5.34%) were the major constituents.
      Oxygenated sesquiterpenes and fatty acids were the main groups of compounds with
      30.7% and 25.85%, respectively. Fifty compounds, representing 96.35% of the total
      oil, were identified in the stem oil. Palmitic acid (13.37), alpha-cadinol
      (9.24%), (epi)-alpha-cadinol (5.76%) and delta-cadenine (6.11%) were the major
      compounds. Sesquiterpenes and oxygenated sesquiterpenes dominated in the oil,
      comprising 28.03% and 20.9%, respectively. The chemical compounds of the
      essential oils showed that there are only 22 common compounds between two parts.

PMID- 20803380
TI  - New polysulphanes from aerial parts of Ferula behboudiana Rech. f. & Esfand.
AB  - The chloroformic extract of the aerial parts of Ferula behboudiana (Umbelliferae)
      afforded four new polysulphane derivatives: 1-sec-butyl-2-[(E)-3-(methylthio)prop
      1-enyl]disulphane (1), 1-sec-butyl-2-[(Z)-3-(methylthio)prop-1-enyl]disulphane
      (2), 1-[(E)-3-(methylthio)prop-1-enyl)-2-(1-(methylthio)propyl]disulphane (3) and
      1-[(Z)-3-(methylthio)prop-1-enyl)-2-(1-(methylthio)propyl]disulphane (4).
      Structural elucidation of diastereomers was carried out easily due to completely
      resolved signals in (1)H NMR spectra and with 2D-NMR techniques.

PMID- 20803381
TI  - Phytochemical investigation of the seeds of Althea officinalis L.
AB  - Phytochemical investigation of the seeds of Althea officinalis L. (Malvaceae) led
      to the isolation of three new phytoconstituents, identified as n-hexacos-2-enyl
      1,5-olide (altheahexacosanyl lactone), 2beta-hydroxycalamene (altheacalamene) and
      5,6-dihydroxycoumarin-5-dodecanoate-6beta-D-glucopyranoside (altheacoumarin
      glucoside), along with the known phytoconstituents lauric acid, beta-sitosterol
      and lanosterol. The structures of these compounds were established on the basis
      of spectral analysis and chemical reactions.

PMID- 20803382
TI  - Chemical constituents of Gentiana macrophylla Pall.
AB  - A novel dimeric secoiridoid glucoside, gentimacroside (1), and six known
      compounds (2-7) were isolated from the roots of Gentiana macrophylla Pall. Their
      structures were established on the basis of spectroscopic analysis, especially by
      means of 1D-, 2D-NMR and HRESIMS analyses.

PMID- 20803383
TI  - Equivalence-based measures of clinical significance: assessing treatments for
      depression.
AB  - Treatment efficacy is largely determined by statistical significance testing, and
      clinical significance testing is often used to quantify or qualify the efficacy
      of a treatment at the individual or group level. This study applies the
      equivalence-based clinical significance model proposed by Kendall, Marrs-Garcia,
      Nath, and Sheldrick (1999) and a revised model proposed by Cribbie and Arpin
      Cribbie (2009) to the assessment of treatments for depression. Using several
      studies that investigated treatments for depression, the authors tested whether
      the posttreatment means were equivalent to those for a similar normal comparison
      group. All of the studies had significant improvement from pretest to posttest,
      although for many of the studies the treated group was not equivalent to a normal
      comparison group at posttest. Further, there are important differences between
      the conclusions drawn from the Kendall et al. and Cribbie and Arpin-Cribbie
      methods for assessing equivalence-based clinical significance.

PMID- 20803384
TI  - Integrated multiple sclerosis care: new approaches and paradigm shifts.

PMID- 20803385
TI  - Compensation examinations for PTSD--an opportunity for treatment?

PMID- 20803386
TI  - Analysis of biomechanical effectiveness of valgus-inducing knee brace for
      osteoarthritis of knee.
AB  - The biomechanical effectiveness of a valgus-inducing knee brace was investigated
      for 16 patients with knee osteoarthritis (mean +/- standard deviation age 56 +/-
      10 yr, height 172 +/- 9 cm, mass 83 +/- 7 kg, body mass index 27.6 +/- 4.5
      kg/m(2)). At the time of investigation, all subjects had been wearing the brace
      for at least 4 weeks. In addition to conducting standard gait analysis, we
      calculated the valgus moment generated by the brace by using a novel system that
      measured the actual deformation of the brace during stance phase and determined
      the reaction force created by the brace on the leg. The mean maximum value of the
      orthotic valgus moment was 0.053 Nm/kg, which represents approximately 10% of the
      external genu varus moment without the brace. This finding may explain the pain
      relief reported by patients using such braces in clinical studies. Use of the
      tested brace also decreased the magnitude of gait asymmetry between the braced
      and contralateral legs during walking (horizontal ground reaction force, external
      knee flexion moment), presumably because the subjects' need to walk abnormally to
      shield the knee from pain was reduced.

PMID- 20803387
TI  - Cost differences in VHA acute and subacute rehabilitation units: implications for
      VHA resource planning.
AB  - Within the Veterans Health Administration (VHA), the top tier of postacute
      rehabilitation care is provided in acute rehabilitation bedservice units (ARBUs).
      The next level of care is provided in subacute rehabilitation bedservice units
      (SRBUs). We fitted reduced-form and structural models to explain VHA cost
      differences between ARBUs and SRBUs across time and for the individual cost
      components. We included sociodemographic variables, time since stroke onset, care
      facility, and the Functional Independence Measure at admission as explanatory
      variables. The multivariable results indicate that total index stay costs are
      lower in ARBUs by almost $6,000 (or approximately 25%) compared with SRBUs.
      Moreover, the lower costs observed in ARBUs in this study combined with the
      higher rates of guideline compliance and improved outcomes in ARBUs found in
      previous work suggest that stroke rehabilitation in an ARBU may be more cost
      effective than stroke rehabilitation in an SRBU.

PMID- 20803388
TI  - Evaluation of aluminum ultralight rigid wheelchairs versus other ultralight
      wheelchairs using ANSI/RESNA standards.
AB  - Previous studies found that select titanium ultralight rigid wheelchairs (TURWs)
      had fewer equivalent cycles and less value than select aluminum ultralight
      folding wheelchairs (AUFWs). The causes of premature failure of TURWs were not
      clear because the TURWs had different frame material and design than the AUFWs.
      We tested 12 aluminum ultralight rigid wheelchairs (AURWs) with similar frame
      designs and dimensions as the TURWs using the American National Standards
      Institute/Rehabilitation Engineering and Assistive Technology Society of North
      America and International Organization for Standardization wheelchair standards
      and hypothesized that the AURWs would be more durable than the TURWs. Across
      wheelchair models, no significant differences were found in the test results
      between the AURWs and TURWs, except in their overall length. Tire pressure, tube
      wall thickness, and tube manufacturing were proposed to be the factors affecting
      wheelchair durability through comparison of the failure modes, frames, and
      components. The frame material did not directly affect the performance of AURWs
      and TURWs, but proper wheelchair manufacture and design based on mechanical
      properties are important.

PMID- 20803389
TI  - Survival of participating and nonparticipating limb amputees in prospective
      study: consequences for research.
AB  - This study quantified selection by analyzing the survival rate of the
      participants and nonparticipants in a 4-year prospective, multicenter cohort
      study. In addition, the differences between these groups were analyzed. Surgeons
      of six hospitals in the northern Netherlands referred, in total, 225 patients to
      the study. Of these patients, 60% (n = 134) participated in the prospective study
      by filling in questionnaires; the others (nonparticipants) were followed over
      time through their records. No significant differences were found in sex and
      level of amputation between participants and nonparticipants; however, of the two
      groups, nonparticipants were significantly older. Reason for amputation was
      peripheral vascular disease (PVD) for 67% (n = 90) of the participants and 82% (n
      = 75) of the nonparticipants. The mean survival time of the participants and
      nonparticipants was 36.1 and 29.6 months, respectively. Within PVD, the mean
      survival time of participants and nonparticipants was 34.4 and 27.6 months,
      respectively.To summarize, our article gives an overview of the survival rates in
      a prospective study on patients scheduled for a limb amputation. Our study sample
      was biased by selection and death. Participants were generally healthier than
      nonparticipants.

PMID- 20803390
TI  - Feasibility study of home telerehabilitation for physically inactive veterans.
AB  - The aim of this study was to develop a system for and determine the feasibility
      of monitoring home exercise for physically inactive older adults using a Health
      Buddy (HB) text messaging device (Robert Bosch Healthcare; Palo Alto,
      California). Questions and messages related to exercise adherence are displayed
      on the HB screen and participants choose a response by pressing the corresponding
      button on the device. Responses are transmitted through a landline connection and
      high-risk responses are highlighted by the system for follow-up. We developed the
      questions and messages based on input from patient and clinician focus groups. We
      evaluated feasibility by administering the intervention to inpatient and
      outpatient adults aged 60 or older. We gave participants a choice of exercise
      monitoring by HB (n = 20) or telephone (n = 18). The results showed that home
      exercise monitoring by HB and telephone is safe, as evidenced by low adverse
      event rates. We saw a decline in exercise adherence rates to both the HB and
      telephone after 8 weeks, although adherence was better for HB than telephone.
      Taken together, the results demonstrate the feasibility of using text messaging
      to monitor home exercise adherence in physically inactive older adults.

PMID- 20803391
TI  - Novel method for measurement of fatigue in multiple sclerosis: Real-Time Digital
      Fatigue Score.
AB  - The study's objective was to develop a real-time measurement for fatigue and to
      evaluate whether it is an effective clinical trial outcome measure compared with
      the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS).
      Forty-nine subjects with MS and an FSS >4 recorded Real-Time Digital Fatigue
      Scores (RDFSs) on a wrist-worn device four times a day over 3 weeks. Scores were
      scaled 0-10, with 10 representing the worst possible fatigue. FSS and MFIS were
      evaluated and compared with RDFSs. Mean RDFSs significantly correlated with FSS
      (r = 0.55, p < 0.001) and MFIS (r = 0.55, p < 0.001). RDFS captured circadian
      variations in fatigue, with scores increasing from mean 3.4 at 9 a.m., to 4.0 at
      1 p.m., 4.5 at 5 p.m., and 5.0 at 9 p.m. When all scores over all days were
      included in a mixed-model analysis of circadian variation, the differences in
      RDFS between times were more significant than in an analysis that included only
      single scores of data isolated from the first day of monitoring. RDFS is a
      promising measure. RDFS significantly correlated with FSS and MFIS, captured real
      time daily and circadian variations in fatigue, and provided multiple
      measurements of fatigue that provided statistical advantages over FSS and MFIS.

PMID- 20803392
TI  - Use of pedometer and Internet-mediated walking program in patients with chronic
      obstructive pulmonary disease.
AB  - We evaluated an Internet-mediated, pedometer-based program to promote walking in
      chronic obstructive pulmonary disease (COPD). First, we assessed the accuracy of
      the Omron HJ-720ITC pedometer (OMRON Healthcare, Inc; Bannockburn, Illinois) in
      51 persons with COPD. The Bland-Altman plot showed a median difference of 3 steps
      (5th and 95th quintiles, -8.0 and 145.0, respectively). We calculated percent
      difference = ([manual - Omron step counts]/manual step counts) x 100. Variability
      in percent difference occurred at the lowest usual walking speeds. At speeds <or=
      0.94 m/s, the mean +/- standard deviation percent difference was 14 +/- 26%.
      Nevertheless, the Omron captured >80% of the manual step counts in 20 of the 23
      persons with walking speed <or= 0.94 m/s. Second, we examined step counts in 24
      persons with COPD who used the Omron and an Internet-mediated, 16-week walking
      program. At baseline, participants with COPD walked an average of 3429 +/- 1502
      steps per day. Sixteen participants completed the program with an average
      increase in daily step count of 988 +/- 1048 steps (p = 0.002). The Omron is
      accurate in persons with COPD with usual walking speeds > 0.94 m/s. Accuracy is
      more variable at lower speeds, but the Omron captures more than 80% of manual
      step counts in most persons.In this preliminary study, an Internet-mediated
      walking program using the Omron significantly increased step counts in COPD.

PMID- 20803393
TI  - Postural control and fear of falling in persons with low-level paraplegia.
AB  - Falls are prevalent reasons for spinal cord injury (SCI). Postinjury fear of
      falling (FOF) can affect rehabilitation potential. We quantified FOF in 15 men
      with paraplegia (ambulatory with bilateral knee-ankle-foot orthoses [KAFOs] and
      elbow crutches) in correlation with their postural control at the center for long
      term SCI rehabilitation of a tertiary-care teaching hospital. Our outcome
      measures comprised the American Spinal Injury Association Impairment Scale, the
      Modified Falls Efficacy Scale (MFES), postural sway measurements in the
      anteroposterior and mediolateral directions; and walking speed, cadence, and
      endurance. We assessed FOF with the MFES followed by measuring postural sway with
      a force platform. We measured gait parameters by asking the participant to
      ambulate on an indoor pathway. The mean postural sway was 314.13 +/- 184.05 mm
      (mean +/- standard deviation) in the anteroposterior direction and 222.16 +/-
      112.34 mm in the mediolateral direction. The MFES score was 41.29 +/- 12.77,
      which showed a statistically significant negative correlation with postural
      control. The self-perception of confidence as measured by MFES might not really
      represent the actual postural stability in individuals with low-level paraplegia.
      FOF can adversely affect the postural control of individuals with low-level
      paraplegia. Clinicians should consider FOF as an influential factor in postural
      control during rehabilitation.

PMID- 20803394
TI  - VA paradigm shift in care of veterans with limb loss.

PMID- 20803395
TI  - DOD paradigm shift in care of servicemembers with major limb loss.

PMID- 20803396
TI  - Paradigm shift for VA amputation care.

PMID- 20803397
TI  - Wounded warriors' perspectives: helping others to heal.

PMID- 20803398
TI  - Expert Panel recommendations--based on research and deliberations from VA HSR&D
      project "impact of the DOD paradigm shift on VA amputee prosthetic care".

PMID- 20803399
TI  - Servicemembers and veterans with major traumatic limb loss from Vietnam war and
      OIF/OEF conflicts: survey methods, participants, and summary findings.
AB  - Care of veterans and servicemembers with major traumatic limb loss from combat
      theaters is one of the highest priorities of the Department of Veteran Affairs.
      We achieved a 62% response rate in our Survey for Prosthetic Use from 298 Vietnam
      war veterans and 283 servicemembers/veterans from Operation Iraqi
      Freedom/Operation Enduring Freedom (OIF/OEF) who sustained major traumatic limb
      loss. Participants reported their combat injuries; health status; quality of
      life; and prosthetic device use, function, rejection, and satisfaction. Despite
      the serious injuries experienced, health status was rated excellent, very good,
      or good by 70.7% of Vietnam war and 85.5% of OIF/OEF survey participants.
      However, many health issues persist for Vietnam war and OIF/OEF survey
      participants (respectively): phantom limb pain (72.2%/76.0%), chronic back pain
      (36.2%/42.1%), residual-limb pain (48.3%/62.9%), prosthesis-related skin problems
      (51.0%/58.0%), hearing loss (47.0%/47.0%), traumatic brain injury (3.4%/33.9%),
      depression (24.5%/24.0%), and posttraumatic stress disorder (37.6%/58.7%).
      Prosthetic devices are currently used by 78.2% of Vietnam war and 90.5% of
      OIF/OEF survey participants to improve function and mobility. On average, the
      annual rate for prosthetic device receipt is 10.7-fold higher for OIF/OEF than
      for Vietnam war survey participants. Findings from this cross-conflict survey
      identify many strengths in prosthetic rehabilitation for those with limb loss and
      several areas for future attention.

PMID- 20803400
TI  - Unilateral upper-limb loss: satisfaction and prosthetic-device use in veterans
      and servicemembers from Vietnam and OIF/OEF conflicts.
AB  - Prosthetic use and satisfaction in wounded servicemembers and veterans with
      unilateral upper-limb loss has not been thoroughly explored. Through a national
      survey, we enrolled 47 participants from the Vietnam conflict and 50 from
      Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) with combat
      associated major unilateral upper-limb loss. Upper-limb prosthetic devices were
      used by 70% of the Vietnam group and 76% of the OIF/OEF group. Mechanical/body
      powered upper-limb devices were favored by the Vietnam group, while a combination
      of myoelectric/hybrid and mechanical/body-powered devices were favored by the
      OIF/OEF group. Upper-limb devices were completely abandoned in 30% of the Vietnam
      and 22% of the OIF/OEF groups. Abandonment was more frequent for transhumeral and
      more proximal levels (42% of Vietnam and 40% of OIF/OEF) than more distal limb
      loss levels. Upper-limb prostheses were rejected because of dissatisfaction with
      the device by significantly fewer (23%) members of the Vietnam group than the
      OIF/OEF group (45%) (p < 0.001). Most common reasons for rejection included pain,
      poor comfort, and lack of functionality. A significant paradigm shift has been
      noted in the OIF/OEF group, who use a greater number and diversity of upper-limb
      prostheses than the Vietnam group.

PMID- 20803401
TI  - Unilateral lower-limb loss: prosthetic device use and functional outcomes in
      servicemembers from Vietnam war and OIF/OEF conflicts.
AB  - Rehabilitation goals following major combat-associated limb loss in World War II
      and the Vietnam war focused on treatment of the injury and a return to civilian
      life. The goal for Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF)
      servicemembers is to restore function to the greatest possible degree and, if
      they desire, return them to Active Duty, by providing them with extensive
      rehabilitation services and a variety of prosthetic devices. Our study determines
      the usefulness of these diverse types of prosthetic devices for restoring
      functional capability and documents prosthesis use and satisfaction. We compare
      servicemembers and veterans with major combat-associated unilateral lower-limb
      loss: 178 from the Vietnam war and 172 from OIF/OEF conflicts. Of survey
      participants with unilateral lower-limb loss, 84% of the Vietnam group and 94% of
      the OIF/OEF group currently use at least one prosthetic device. Reasons for
      rejection varied by type of device, but common reasons were pain, prosthesis too
      heavy, and poor fit. Abandonment is infrequent (11% Vietnam group, 4% OIF/OEF
      group). Future efforts should aim to improve prosthetic-device design, decrease
      pain, and improve quality of life for these veterans and servicemembers.

PMID- 20803402
TI  - Multiple traumatic limb loss: a comparison of Vietnam veterans to OIF/OEF
      servicemembers.
AB  - Multiple-limb loss due to war-theater injuries results in a unique group of
      servicemembers requiring intensive rehabilitation and diverse prosthetic devices.
      This article compares the Vietnam and the Operation Iraqi Freedom/Operation
      Enduring Freedom (OIF/OEF) groups with war-theater-associated multiple-limb loss
      to document significant changes in health status, prosthetic-device use, and long
      term prognosis. During 2007 and 2008, a national survey queried 73 Vietnam
      veterans and 61 OIF/OEF servicemembers sustaining multiple-limb loss. Average
      years since limb loss are 39 for Vietnam veterans and 3 for OIF/OEF
      servicemembers. Self-rated health status was excellent or very good in 38.9% of
      the Vietnam group and 60.7% of the OIF/OEF group (p = 0.01). More of the OIF/OEF
      group than the Vietnam group reported performing high-impact aerobic activities,
      18% versus 3% (p = 0.005). The OIF/OEF group currently uses more diverse
      prosthetic-device types than the Vietnam group. Based on Vietnam veterans' 39
      year experience, the long-term prognosis for OIF/OEF servicemembers with multiple
      limb loss is an active, fulfilling life. The healthcare team caring for these
      patients should carefully address proper prosthesis fit and maintenance of good
      health and function.

PMID- 20803403
TI  - Wheeled mobility: factors influencing mobility and assistive technology in
      veterans and servicemembers with major traumatic limb loss from Vietnam war and
      OIF/OEF conflicts.
AB  - Returning wounded veterans and servicemembers to their highest level of function
      following traumatic injury is a priority of the Departments of Defense and
      Veterans Affairs. We surveyed 245 veterans from the Vietnam war and 226
      servicemembers and veterans from Operation Iraqi Freedom/Operation Enduring
      Freedom (OIF/OEF) conflicts with at least one major traumatic lower-limb loss to
      determine their use of mobility assistive technology (AT) and patterns of limb
      abandonment. Prosthetic device use without wheelchair use is found in 50.5% of
      Vietnam and 42.8% of OIF/OEF groups. Prostheses and supplementary wheelchairs are
      used by Vietnam (32%) and OIF/OEF (53%) groups (p < 0.01). Exclusive wheelchair
      use is more frequent in the Vietnam group (18%) than in the OIF/OEF group (4.0%,
      p < 0.01). In Vietnam participants, multivariate analysis found that multiple
      limb loss (adjusted odds ratio [AOR] = 14.5; 95% confidence interval [CI] 5.5
      38.5), bilateral lower-limb loss (AOR = 12.7; 95% CI 6.2-26.1), and number of
      comorbidities (AOR = 1.3; 95% CI 1.2-1.5) are associated with increased
      likelihood of wheelchair use. In OIF/OEF participants, bilateral lower-limb loss
      (AOR = 29.8; 95% CI 11.0-80.7), multiple-limb loss (AOR = 16.3; 95% CI 3.1-85.3),
      cumulative trauma disorder (AOR = 2.4; 95% CI 1.2-4.9), and number of combat
      injuries (AOR = 1.4; 95% CI 1.2-1.7) are associated with wheelchair use. Combined
      use of different types of mobility ATs promotes improved rehabilitation and
      ability to function.

PMID- 20803404
TI  - Comparison of satisfaction with current prosthetic care in veterans and
      servicemembers from Vietnam and OIF/OEF conflicts with major traumatic limb loss.
AB  - Prosthetic care is a vital aspect of healthcare and rehabilitation for veterans
      and servicemembers with major traumatic limb loss. Our survey queried 581
      veterans and servicemembers with limb loss from the Vietnam and Operation Iraqi
      Freedom (OIF)/Operation Enduring Freedom (OEF) conflicts. Among survey
      participants, 78.2% from the Vietnam conflict and 90.5% from the OIF/OEF conflict
      currently use prosthetic devices. In Vietnam respondents, 78% received prosthetic
      care from private sources, 16% from Department of Veterans Affairs (VA)
      prosthetic laboratories, 0.9% from Department of Defense (DOD), and 5% from
      multiple sources. In OIF/OEF respondents, 42% received prosthetic care from
      private sources, 9% percent from VA, 39% from DOD, and 10% from multiple sources.
      Participants identified their satisfaction with current prosthetic devices and
      prosthetic services. Reports of pain, sweating, skin irritation, and problems
      with socket fit continue to be significant issues for participants from both
      conflicts regardless of level of amputation or site of service. In those with
      upper-limb loss who used myoelectric prostheses, minimal effect on prosthesis use
      and satisfaction was noted. Among lower-limb loss participants from both
      conflicts, notable differences existed in prosthesis satisfaction by source of
      care.

PMID- 20803405
TI  - Quality of life for veterans and servicemembers with major traumatic limb loss
      from Vietnam and OIF/OEF conflicts.
AB  - The goals of rehabilitation after major limb loss include not only functional
      restoration but also a return to a high quality of life (QOL). Few studies have
      identified which factors are associated with QOL in veterans and servicemembers
      with combat-associated major limb loss. We enrolled Vietnam and Operation Iraqi
      Freedom/Operation Enduring Freedom (OIF/OEF) veterans and servicemembers in a
      national survey on prosthetic device use. In the Vietnam group, multivariate
      analysis found multiple limb loss (adjusted odds ratio [aOR] = 3.1, 95%
      confidence interval [CI] = 1.57-6.02) and satisfaction with current prostheses
      (aOR = 1.2, 95% CI = 1.05-1.38) are associated with better overall QOL, while a
      higher amputation impact rank (aOR = 0.66, 95% CI = 0.59-0.74) and depression
      (aOR = 0.21, 95% CI = 0.08-0.54) are associated with worse overall QOL. In the
      OIF/OEF group, three factors are significantly associated with worse overall QOL:
      combat-associated head injury (aOR = 0.78, 95% CI = 0.61-0.99), combat-associated
      injury to the nonamputated limb (aOR = 0.71, 95% CI = 0.57-0.88), and assistance
      needed in daily living (aOR = 0.12, 95% CI = 0.02-0.72). Improving satisfaction
      with prosthetic devices, improving mental health care, and treating other combat
      associated injuries may significantly improve the overall QOL for these veterans
      and servicemembers.

PMID- 20803406
TI  - Prosthetic cost projections for servicemembers with major limb loss from Vietnam
      and OIF/OEF.
AB  - This study projects prosthetic- and assistive-device costs for veterans with limb
      loss from Vietnam and injured servicemembers returning from Operation Iraqi
      Freedom (OIF) and Operation Enduring Freedom (OEF) to inform the Department of
      Veterans Affairs (VA) for these veterans' future care. The 2005 Medicare
      prosthetic device component prices were applied to current prosthetic and
      assistive-device use obtained from a national survey of 581 veterans and
      servicemembers with major traumatic amputations. Projections were made for 5
      year, 10-year, 20-year, and lifetime costs based on eight Markov models. Average
      5-year projected costs for prosthetic and assistive-device replacement for the
      Vietnam group are lower than for the OIF/OEF cohort due in part to use of fewer
      and less technologically advanced prosthetic devices and higher frequency of
      prosthetic abandonment. By limb-loss level, for the Vietnam group and OIF/OEF
      cohort, 5-year projected unilateral upper limb average costs are $31,129 and
      $117,440, unilateral lower limb costs are $82,251 and $228,665, and multiple limb
      costs are $130,890 and $453,696, respectively. These figures provide the VA with
      a funding estimate for technologically advanced prosthetic and assistive devices
      within the framework of ongoing rehabilitation for veterans with traumatic limb
      loss from the Vietnam and OIF/OEF conflicts.

PMID- 20803407
TI  - Department of Veterans Affairs compensation and medical care benefits accorded to
      veterans with major limb loss.
AB  - Veterans injured in theaters of combat operations are eligible for benefits,
      including medical care and compensation. This article describes veterans with
      service-connected disability for major lower- and/or upper-limb loss resulting
      from combat-field-associated injuries sustained in the Vietnam war, Operation
      Desert Shield/Operation Desert Storm, and Operation Iraqi Freedom/Operation
      Enduring Freedom (OIF/OEF). Using the Department of Veterans Affairs (VA)
      Compensation and Pension Mini-Master file, we identified 2,690 veterans who in
      August 2007 received compensation for loss of one or more limbs. More than 97%
      sustained their injuries in Vietnam; most were young men who served in the U.S.
      Army or Marine Corps. All but 5% had at least 50% combined service-connected
      disability and nearly half had a 100% rating. In addition to limb loss, one of
      the most prevalent compensable conditions was posttraumatic stress disorder,
      present in 46% of OIF/OEF and 20% of Vietnam veterans. Of these veterans, 82%
      visited VA outpatient clinics in 2007, although only 4% were hospitalized. A
      special obligation exists to those who have sustained serious injuries related to
      combat; this responsibility extends for the life of the servicemember and beyond
      to his or her spouse and dependents.

PMID- 20803408
TI  - [Mind meets body--the comorbid patient as a true challenge of
      interdiscipinarity].

PMID- 20803409
TI  - [Lifelong relapse prevention with antipsychotics in schizophrenia].

PMID- 20803410
TI  - [Diagnostics and therapy of alcohol withdrawal syndrome: focus on delirium
      tremens and withdrawal seizure].
AB  - INTRODUCTION: Delirium tremens and withdrawal seizures are serious complications
      of an alcohol withdrawal syndrome. This review presents the diagnostic procedures
      required in case of the occurrence of a withdrawal seizure and delirium tremens
      as well as possible treatment options including prophylactic medication regimen
      for alcohol withdrawal syndrome. Furthermore non-pharmacological procedures
      accompanying delirium tremens and a potential integration of viewing videotapes
      of delirium tremens in the course of alcohol-specific therapy are discussed.
      METHODS: A systematic literature research using Pubmed has been carried out to
      find recent studies and review articles dealing with alcohol withdrawal syndrome.
      RESULTS AND DISCUSSION: Regarding the diagnostic algorithm in case of the
      occurrence of a withdrawal seizure or a delirium tremens basic diagnostic
      procedures and special diagnostics including neuro-imaging or cerebrospinal fluid
      puncture depending on patients' clinical condition have to be considered.
      Sedatives are important in treatment of alcohol withdrawal seizures and delirium
      tremens as well as in the prophylaxis of alcohol withdrawal syndrome. A long
      lasting prescription of anticonvulsant medication in patients suffering from
      withdrawal seizure should be considered critically and can be carried out only
      under certain conditions.

PMID- 20803411
TI  - [Catatonic dilemma in a schizoaffective patient with combined lithium-risperidone
      administration].
AB  - OBJECTIVE: The case of a schizoaffective patient suffering from a malignant
      catatonic syndrome following combined lithium-risperidone therapy is explored.
      METHOD: A case report and relevant deliberations regarding pathophysiology of the
      catatonic dilemma are discussed. CONCLUSIONS: There are two critical transitions
      in the development of a malignant catatonic syndrome. Dopaminergic system and
      psychopharmacological factors are supposed to play a key role. However, other
      neurotransmitter systems and the individual predisposition must be considered.

PMID- 20803412
TI  - High spatial resolution and high contrast visualization of brain arteries and
      veins: impact of blood pool contrast agent and water-selective excitation imaging
      at 3T.
AB  - PURPOSE: To investigate a blood pool contrast agent and water-selective
      excitation imaging at 3 T for high spatial and high contrast imaging of brain
      vessels including the veins. METHODS AND RESULTS: 48 clinical patients (47 +/- 18
      years old) were included. Based on clinical findings, twenty-four patients
      received a single dose of standard extracellular Gadoterate-meglumine
      (Dotarem(r)) and 24 received the blood pool contrast agent Gadofosveset
      (Vasovist(r)). After finishing routine MR protocols, all patients were
      investigated with two high spatial resolution (0.15 mm (3) voxel size) gradient
      echo sequences in random order in the equilibrium phase (steady-state) as
      approved by the review board: A standard RF-spoiled gradient-echo sequence (HR
      SS, TR/TE 5.1/2.3 msec, FA 30 degrees ) and a fat-suppressed gradient-echo
      sequence with water-selective excitation (HR-FS, 1331 binominal-pulse, TR/TE
      8.8/3.8 msec, FA 30 degrees ). The images were subjectively assessed (image
      quality with vessel contrast, artifacts, depiction of lesions) by two
      investigators and contrast-to-noise ratios (CNR) were compared using the
      Student's t-test. The image quality and CNR in the HR-FS were significantly
      superior compared to the HR-SS for both contrast agents (p < 0.05). The CNR was
      also improved when using the blood pool agent but only to a minor extent while
      the subjective image quality was similar for both contrast agents. CONCLUSION:
      The utilized sequence with water-selective excitation improved image quality and
      CNR properties in high spatial resolution imaging of brain arteries and veins.
      The used blood pool contrast agent improved the CNR only to a minor extent over
      the extracellular contrast agent.

PMID- 20803413
TI  - The anti-adipogenic effect of macrophage-conditioned medium requires the
      IKKbeta/NF-kappaB pathway.
AB  - Macrophage-secreted factors inhibit adipogenesis, but the underlying mechanism is
      not well understood. Our objective was to determine if anti-adipogenic signaling
      pathways in human preadipocytes are activated by macrophage-conditioned medium
      (MacCM). Human abdominal subcutaneous stromal preadipocytes were treated with
      adipogenic inducers in either standard medium or medium conditioned by human THP
      1 macrophages. THP-1-MacCM increased inhibitor of kappaB kinase beta (IKKbeta)
      phosphorylation, inhibitor of NF-kappaB alpha (IkappaBalpha) degradation, and NF
      kappaB activity in human preadipocytes in a time-dependent manner. Concomitant
      treatment of human abdominal subcutaneous preadipocytes with sc-514, a selective
      inhibitor of IKKbeta, prevented the inhibitory effect of THP-1-MacCM on lipid
      accumulation and expression of adipogenic markers. Our data indicate that
      activation of the preadipocyte IKKbeta/NF-kappaB pathway is required for the anti
      adipogenic effect of THP-1-MacCM on human adipogenesis.

PMID- 20803414
TI  - Dietary folic acid activates AMPK and improves insulin resistance and hepatic
      inflammation in dietary rodent models of the metabolic syndrome.
AB  - The AMP activated kinase plays an important role in metabolic control, and
      pharmacologic enhancement of AMPK activity is used to improve insulin resistance.
      We hypothesized that high dose of folic acid supplementation might improve
      insulin sensitivity and hepatic inflammation and examined this by a dietary
      intervention in (a) the high fat fed rat model of the metabolic syndrome, which
      shows sole hepatic steatosis as well as (b) in rats fed with a high cholesterol,
      high cholate diet inducing nonalcoholic steatohepatitis (NASH). Male Wistar rats
      were fed with folic acid supplemented (40 mg/kg) high fat diet [based on lard,
      fat content 25% (wt/wt)] or NASH inducing diet (containing 15% fat, 1.25%
      cholesterol, 0.5% sodium cholate). Metabolic profiling was performed by measuring
      the animals' visceral fat pads, fasting plasma glucose, insulin, and adipokines
      as well as in vivo insulin tolerance tests. Hepatic steatosis and inflammation
      were analyzed semiquantitatively by histological analysis. Folic acid
      supplementation reduced visceral obesity and improved plasma adiponectin levels.
      In vivo insulin sensitivity was improved, and in HF-FA rats folic acid increased
      activation of hepatic AMPK. Further, folic acid supplementation improved hepatic
      inflammation in animals fed with NASH-inducing diet. Dietary folic acid improved
      parameters of insulin resistance and hepatic inflammation in rodent models. This
      might be due to an increased AMK activation.

PMID- 20803416
TI  - DNA barcoding of Panax species.
AB  - Ginsengs (Panax, Araliaceae) are among the plants best known for their medicinal
      properties. Many ginseng species are endangered due to over-exploitation of
      natural resources - a situation difficult to remedy while there are no reliable,
      practical methods for species identification. We screened eleven candidate DNA
      barcoding loci to establish an accurate and effective Panax species
      identification system, both for commercial and conservation purposes. We used 95
      ginseng samples, representing all the species in the genus. We found considerable
      differences in the performance of the potential barcoding regions. The sequencing
      of ATPF-ATPH was unsuccessful due to poly-N structures. The RBCL, RPOB, and RPOC1
      regions were found to be mostly invariable, with only four to eight variable
      sites. Using MATK, PSBK-I, PSBM-TRND, RPS16 and NAD1, we could identify four to
      six out of eight considerably divergent species but only one to five out of
      nineteen clusters within the P. bipinnatifidus species group. PSBA-TRNH and ITS
      were the most variable loci, working very well both in species and cluster
      identifications. We demonstrated that the combination of PSBA-TRNH and ITS is
      sufficient for identifying all the species and clusters in the genus.

PMID- 20803417
TI  - Cajanol inhibits the growth of Escherichia coli and Staphylococcus aureus by
      acting on membrane and DNA damage.
AB  - In the present study, the mechanism of antibacterial activity of cajanol
      extracted from the roots of Cajanus cajan (L.) Millsp. towards Escherichia coli
      (E. coli) and Staphylococcus aureus (S. aureus) was investigated. The
      antibacterial activity of cajanol was evaluated towards six bacterial strains
      (Staphylococcus epidermidis, Staphylococcus aureus, Bacillus subtilis,
      Escherichia coli, Proteus vulgaris, and Pseudomonas aeruginosa) by the broth
      microdilution method. It showed strong antibacterial activity towards all
      bacteria tested with minimal inhibition concentration (MIC) values ranging from
      98.90 uM to 197.8 uM. Cajanol-induced death rates in the most sensitive strains (
      E.COLI, 96.55 % and S. AUREUS, 97.25 %) were analyzed by flow cytometry.
      Furthermore, the activity of cajanol on the membranes of E. coli and S. aureus
      was investigated by using lecithin, phosphate groups, and fluorescence
      microscopy. Cajanol-induced DNA damage was observed by agarose gel
      electrophoresis. In summary, cajanol inhibited E. coli only by DNA damage,
      whereas S. aureus was inhibited by affecting both, the lecithin and phosphate
      groups on the cellular membrane and DNA. The present study shows that cajanol
      possesses antibacterial activity in vitro towards both gram-negative and gram
      positive bacteria and therefore may be a promising candidate as an antibacterial
      agent for the therapy of microbial infections.

PMID- 20803415
TI  - High prevalence of normal tests assessing hypercortisolism in subjects with mild
      and episodic Cushing's syndrome suggests that the paradigm for diagnosis and
      exclusion of Cushing's syndrome requires multiple testing.
AB  - Many Endocrinologists believe that a single determination of eucortisolism or a
      single demonstration of appropriate suppression to dexamethasone excluded
      Cushing's syndrome, except in what was previously thought to be the rare patient
      with episodic or periodic Cushing's syndrome. We hypothesize that episodic
      Cushing's syndrome is relatively common and a single test assessing
      hypercortisolism may not be sufficient to accurately rule out or diagnose
      Cushing's syndrome and retrospectively examined the number of normal and abnormal
      tests assessing hypercortisolism performed on multiple occasions in 66 patients
      found to have mild and/or episodic Cushing's syndrome compared to a similar group
      of 54 patients evaluated for, but determined not to have Cushing's syndrome. We
      found that 65 of the 66 patients with Cushing's syndrome had at least one normal
      test of cortisol status and most patients had several normal tests. The
      probability of having Cushing's syndrome when one test was negative was 92% for
      23:00 h salivary cortisol, 88% for 24-h UFC, 86% for 24-h 17OHS, and 54% for
      nighttime plasma cortisol. These results demonstrated that episodic
      hypercortisolism is highly prevalent in subjects with mild Cushing's syndrome and
      no single test was effective in conclusively diagnosing or excluding the
      condition. Rather, the paradigm for the diagnosis should be a careful history and
      physical examination and in those patients in whom mild Cushing's
      syndrome/disease is strongly suspected, multiple tests assessing hypercortisolism
      should be performed on subsequent occasions, especially when the patient is
      experiencing signs and symptoms of short-term hypercortisolism.

PMID- 20803418
TI  - Crocetin inhibits invasiveness of MDA-MB-231 breast cancer cells via
      downregulation of matrix metalloproteinases.
AB  - Crocetin is a carotenoid dicarboxylic acid which, in nature, is esterified with
      glucose or gentiobiose units forming the crocins, abundant components of saffron
      (a spice with many reputed medicinal uses). We have previously reported that
      saffron, crocins and crocetin inhibit breast cancer cell proliferation. In order
      to further study the effect of crocetin on breast cancer cells, we used the
      highly invasive MDA-MB-231 cells and measured the viability with the WST-1 assay
      and the invasiveness through a reconstituted basement membrane. After 24 h
      incubation, crocetin significantly inhibited not only proliferation but also
      invasion at 1 and 10 uM. Cancer invasiveness and metastasis are associated with
      the expression of matrix metalloproteinases (MMPs). In order to study the
      molecular changes of MMP expression that might accompany the observed crocetin
      effects, gene expression of MMPs was studied by RT-PCR, whereas protein
      expression and gelatinolytic activity were determined with Western blotting and
      zymography, respectively. The gene and protein expression of pro-MT1-MMP and pro
      MT2-MMP were greatly attenuated by both crocetin and all- TRANS-retinoic acid
      (ATRA, used as control). Incubation with 10 uM crocetin for 24 h in serum-free
      conditions reduced pro-MMP-9 activity and pro-MMP-2/MMP-2 protein levels. When
      cultured in media with sera 2 and 5 %, crocetin at 10 MUMU also reduced
      gelatinase activity. The above findings show that crocetin, the main metabolite
      of crocins, inhibits MDA-MB-231 cell invasiveness via downregulation of MMP
      expression.

PMID- 20803419
TI  - High definition colonoscopy combined with i-Scan is superior in the detection of
      colorectal neoplasias compared with standard video colonoscopy: a prospective
      randomized controlled trial.
AB  - INTRODUCTION: Colonoscopy is the accepted gold standard for the detection of
      colorectal cancer. The aim of the current study was to prospectively compare high
      definition plus (HD+) colonoscopy with I-Scan functionality (electronic staining)
      vs. standard video colonoscopy. The primary endpoint was the detection of
      patients having colon cancer or at least one adenoma. METHODS: A total of 220
      patients due to undergo screening colonoscopy, postpolypectomy surveillance or
      with a positive occult blood test were randomized in a 1 : 1 ratio to undergo HD+
      colonoscopy in conjunction with I-Scan surface enhancement (90i series, Pentax,
      Tokyo, Japan) or standard video colonoscopy (EC-3870FZK, Pentax). Detected
      colorectal lesions were judged according to type, location, and size. Lesions
      were characterized in the HD+ group by using further I-Scan functionality (p- and
      v-modes) to analyze pattern and vessel architecture. Histology was predicted and
      biopsies or resections were performed on all identified lesions. RESULTS: HD+
      colonoscopy with I-Scan functionality detected significantly more patients with
      colorectal neoplasia (38 %) compared with standard resolution endoscopy (13 %)
      (200 patients finally analyzed; 100 per arm). Significantly more neoplastic
      (adenomatous and cancerous) lesions and more flat adenomas could be detected
      using high definition endoscopy with surface enhancement. Final histology could
      be predicted with high accuracy (98.6 %) within the HD+ group. CONCLUSIONS: HD+
      colonoscopy with I-Scan is superior to standard video colonoscopy in detecting
      patients with colorectal neoplasia based on this prospective, randomized,
      controlled trial.

PMID- 20803420
TI  - Prospective comparison between double-balloon enteroscopy and spiral enteroscopy.
AB  - BACKGROUND AND STUDY AIMS: Push enteroscopy, balloon-guided, and single- and
      double-balloon enteroscopy (DBE) are now well established techniques in
      gastrointestinal endoscopy for small-bowel imaging and therapy. There are no
      published prospective studies comparing DBE with spiral enteroscopy and so the
      aim of the current study was to compare the performance of the two techniques in
      patients undergoing diagnostic enteroscopy. PATIENTS AND METHODS: Between January
      and December 2009, 35 patients referred for diagnostic enteroscopy were
      prospectively assigned to either spiral enteroscopy (n=18) or DBE (n=17). The
      performance of the two techniques was compared. RESULTS: The patients were
      comparable with regard to age, sex, and indication for enteroscopy. Investigation
      performance, as assessed by time of insertion into the pylorus, the depth of
      insertion, the duration of the enteroscopy, and the amount of sedoanalgesia
      required were not significantly different between spiral enteroscopy and DBE. In
      40% of the investigations, enteroscopy could detect abnormalities in the
      intestinal mucosa, in particular inflammatory changes and ulcers and, to a lesser
      extent, angiodysplasia. No significant difference in pathological findings could
      be detected between the two groups; however, clinically, diagnostic yield
      appeared to be higher for DBE (47.1% vs. 33.4%; n.s.). CONCLUSION: Although this
      small study appears to show that DBE has a clinically higher diagnostic yield
      than spiral enteroscopy, larger studies are needed to confirm this preliminary
      finding.

PMID- 20803421
TI  - [Healthy diet: controlling with taxes?].

PMID- 20803423
TI  - The effects of uncoupling protein 1 and beta3-adrenergic receptor gene
      polymorphisms on weight loss and lipid profiles in obese women.
AB  - The purpose of this study was to investigate whether the genetic polymorphisms of
      the uncoupling protein 1 (UCP1) and beta 3 adrenergic receptor (beta3-AR) were
      associated with differences in weight loss and lipid profiles in obese
      premenopausal women exposed to low-calorie meal replacements over a period of six
      weeks. Forty women between the ages of 20 and 35 were randomly divided into two
      groups, each of which consumed one of two low-calorie meal replacements
      containing either white rice or mixed rice. Although body weight, body mass index
      (BMI), blood glucose concentration, triglycerides, total cholesterol (TC), and
      high-density lipoprotein cholesterol (HDL-C) were not significantly different by
      the UCP1 genotype in the white rice group, there were significant differences in
      body weight (p = 0.041), BMI (p = 0.027), and blood glucose concentration (p =
      0.047) between carriers and non-carriers of the G allele in the mixed rice group
      after the six-week meal replacement intervention. The beta3-AR polymorphism
      showed no apparent affect on these parameters. Dietary fiber affects weight gain
      since it is closely related with absorption of nutrients. As a result, the AA
      type UCP1 genotype produced significant weight loss in the mixed rice group, but
      not in the white rice group.

PMID- 20803424
TI  - The effects of yellow soybean, black soybean, and sword bean on lipid levels and
      oxidative stress in ovariectomized rats.
AB  - Soy isoflavones have been reported to decrease the risk of atherosclerosis in
      postmenopausal women. However, the effects of dietary consumption of soybean have
      not been explored. In this study, we evaluated the effects of consuming yellow
      soybeans, black soybeans (Glycine max), or sword beans (Canavalia gladiate) on
      lipid and oxidative stress levels in an ovariectomized rat model. Forty-seven
      nine-week-old female rats were ovariectomized, randomly divided into four groups,
      and fed one of the following diets for 10 weeks: a diet supplemented with casein
      (NC, n = 12), a diet supplemented with yellow soybean (YS, n = 12), a diet
      supplemented with black soybean (BS, n = 12), or a diet supplemented with sword
      bean (SB, n = 11). Plasma triglyceride (TG) levels in the BS and SB groups were
      significantly lower than that in the NC group. Notably, the BS group had
      significantly lower plasma total cholesterol (TC), and low-density lipoprotein
      cholesterol (LDL-C) levels than the other groups. Hepatic total lipid levels were
      significantly lower in the YS and SB groups, and cholesterol levels were
      significantly lower in the SB group than in the NC group. Superoxide dismutase
      (SOD) and catalase (CAT) activities were significantly higher in the groups fed
      beans compared to the NC group. Hepatic thiobarbituric acid reactive substances
      (TBARS) levels were also significantly lower in the BS and SB groups than the NC
      group. In conclusion, our results suggest that consumption of various types of
      beans may inhibit oxidative stress in postmenopausal women by increasing
      antioxidant activity and improving lipid profiles. Notably, intake of black
      soybean resulted in the greatest improvement in risk factors associated with
      cardiovascular disease.

PMID- 20803425
TI  - The effects of low dose n-3 fatty acids on serum lipid profiles and insulin
      resistance of the elderly: a randomized controlled clinical trial.
AB  - INTRODUCTION: N-3 fatty acids have several beneficial effects on dyslipidemia and
      diabetes, conditions which are prevalent in the elderly. This study assessed the
      effects of low-dose n-3 fatty acids on serum lipid profile, lipoprotein(a),
      apolipoprotein B, fasting glucose, insulin, and insulin resistance in a group of
      elderly Iranians. MATERIALS AND METHODS: A 6-month randomized, double-blind
      placebo-controlled clinical trial was carried out in 124 elderly residents of
      Kahrizak Charity Foundation aged >or= 65. The intervention group was supplemented
      with 1 g/day fish oil capsule (with 180 mg eicosapentaenoic acid, EPA; and 120 mg
      docosahexaenoic acid, DHA; a total of 300 mg n-3 fatty acids as effective
      constituents). Fasting blood samples were collected at baseline and after 6
      months of the trial. RESULTS: There were no significant effects of fish oil on
      the studied variables in the intervention group. In the placebo group, serum
      triglyceride significantly increased and high-density lipoprotein cholesterol
      significantly decreased (p = 0.01 and p = 0.009, respectively). By repeated
      measurement analysis after adjustments, the overall decrease in serum
      triglycerides compared with placebo was significant (p = 0.04). CONCLUSION:
      Supplementation with low dose n-3 fatty acids for 6 months could significantly
      protect elderly Iranians from a rise in serum triglycerides.

PMID- 20803426
TI  - Vitamin a supplements alleviate inflammatory responses in reproductive tracts of
      male mice infected with pseudorabies virus.
AB  - Vitamin A is largely thought to have immune potential for mammal health; however,
      no conclusive mechanisms exist regarding its role in the pathogen-initiated
      innate immune response, or in the linkage between the innate and adaptive immune
      system during sperm formation in the male reproductive tract. Therefore, this
      study was conducted to evaluate the nutritional protective effect of vitamin A
      supplementation on reproductive performance and immune function of the male mouse
      challenged with pseudorabies virus (PRV). Sperm quality, testis toll-like
      receptors (TLRs) mRNA expression levels, and serum concentration of cytokines and
      immunoglobulins at 7 or 14 days post-injection were compared between control mice
      and PRV-challenged mice fed the same diet supplemented with vitamin A at 0, 4000,
      10,000, 25,000 and 50,000 IU/kg, respectively. PRV- and phosphate buffered saline
      (PBS)-injection were performed when the mice in the unsupplemented group were
      marginally deficient in vitamin A. Sperm quality (sperm density and deformity
      ratio) of PRV-injected mice was significantly harmed by PRV, but this effect was
      attenuated by increased vitamin A consumption. Vitamin A supplements also
      attenuated PRV-challenge-induced increase in testis TLR3, TLR7, and TLR9 mRNA
      expression and serum pro-inflammatory cytokine (gamma interferon, IFN-gamma; and
      interleukin 1-beta,IL-1beta) concentration, and decrease in serum anti
      inflammatory cytokine (IL-10) concentration. Higher than normal vitamin A
      consumption was recommended to counteract the deleterious effects of viral
      invasion, possibly through the downregulated expression of TLRs, and thus to
      improve immunity and reproductivity of male mice challenged with an invading
      pathogen.

PMID- 20803427
TI  - Effect of some natural mineral waters in nutrient uptake by Caco-2 cells.
AB  - We studied the effect of some mineral waters and some of their constituents on
      the apical uptake of (14)C-butyrate ((14)C-BT) and (3)H-O-methyl-D-glucose ((3)H
      OMG) by Caco-2 cells. Uptake of (14)C-BT increased after a 20-minute exposure to
      1 % (v/v) distilled water, and, compared to distilled water, it was decreased by
      Pedras Salgadas((R)) 1 % (v/v) and Melgaco((R)) 5 % (v/v), and increased by
      Vidago((R)) 5 % (v/v). Moreover, it increased after a 48-hour exposure to
      Vidago((R)) or Melgaco((R)) waters (5 % (v/v)). Also, uptake of (14)C-BT was
      reduced after a 20-minute exposure to MgCl(2), MgSO(4), or CaCl(2). Uptake of
      (3)H-OMG was reduced after a 20-minute exposure to Melgaco((R)) water [1 %
      (v/v)], when compared to distilled water. Also, a 48-hour exposure to Pedras
      Salgadas((R)) or Melgaco((R)) water (5 % (v/v)) increased and decreased uptake,
      respectively. Finally, uptake of (3)H-OMG decreased after a 20-minute exposure to
      MgSO(4) or NaF. In conclusion, uptake of (14)C-BT and (3)H-OMG by Caco-2 cells is
      differently modulated by distinct mineral waters.

PMID- 20803428
TI  - Iron, folate, and B(12) deficiencies and their associations with anemia among
      women of childbearing age in a rural area in Northern China.
AB  - OBJECTIVE: To assess the prevalence of folate, vitamin B(12), and iron
      deficiencies and their associations with anemia among women of childbearing age
      in northern China, an area with a reported high incidence of neural tube defects.
      METHODS: Plasma folate, vitamin B(12), ferritin, and hemoglobin levels were
      measured among 1,671 non-pregnant women of childbearing age from Xianghe County,
      Hebei Province, China in June 2004. RESULTS: Geometric means [95 % confidence
      interval (CI)] of plasma concentrations were 9.3 (4.0, 21.6) nmol/L for folate,
      213.1 (82.4, 550.9) pmol/L for vitamin B(12), 17.4 (1.1, 278.6) microg/L for
      ferritin, and 129.9 (104.6, 161.4) g/L for hemoglobin (Hb). Approximately 24 % of
      women had biochemical evidence of folate deficiency (<6.8 nmol/L), 21.4 % were
      deficient (<148 pmol/L) in vitamin B(12), 30.2 % had iron depletion (<15
      microg/L), and anemia (Hb < 120 g/L) was detected among 15.4 % of women. Of the
      three nutrients, only iron depletion (ferritin < 15 microg/L) was independently
      associated with anemia (adjusted odds ratio = 6.4, 95 % CI 4.8, 8.6).
      CONCLUSIONS: Although there were substantial proportions of folate and vitamin
      B(12) deficiencies among women of childbearing age in northern China, iron
      deficiency was the most important contributor to anemia.

PMID- 20803429
TI  - The role of fretting damage in total hip arthroplasty with modular design hip
      joints -evaluation of retrieval studies and experimental simulation methods.
AB  - Retrieval studies of total hip arthroplasty were reviewed to assess the clinical
      relevance of fretting damage on the clinical outcome of total hip arthroplasty
      with modular design artificial hip joints. In this case, fretting denotes the
      small rel-ative displacement between the two contacting surfaces at the taper
      joint of a modular hip prosthesis under cyclic loading caused by walking.
      Fretting causes a local disruption of the passivation surface layer exposing new
      metal to the aggressive body envi-ronment. The most important consequence is the
      release of metal ions and small particles. In spite of evidence that fretting
      plays a role in the corrosion of taper joints in modular hip implants, the
      statistics of the retrieval studies is too poor for a quantita-tive assessment.
      Moreover, the complexity of interacting mechanical loading, surface damage and
      corrosion leads to apprecia-ble difficulties in the experimental description of
      the phenomenon and the terminology used. A rather exhaustive list of experi
      mental methods for in vitro fretting testing is presented. The difficulties
      related with accelerated testing using excessive dis-placement amplitudes or high
      frequencies are discussed. The necessity for alternative methods that allow in
      situ monitoring of metal ion and particle release with sufficient sensitivity
      under meaningful experimental conditions has been underlined. As an alternative
      to electrochemical methods, the possibility to measure subnanogram material
      release by using radiotracer techniques is demonstrated. (Journal of Applied
      Biomaterials & Biomechanics 2004; 2: 121-35).

PMID- 20803430
TI  - The influence of bovine serum lubricant on the wear of cross-linked polyethylene
      finger prostheses.
AB  - A two-piece finger prosthesis has been proposed, manufactured from silane cross
      linked polyethylene. Using a finger wear simulator the prosthesis was tested in a
      dilute bovine serum lubricant. Five tests were undertaken, totalling over 45
      million cycles of wear testing. In each test, a statically loaded control
      prosthesis was included. In all tests it was found that the lubricant uptake of
      the test components exceeded that of the control components, consequently no
      gravimetric wear was measured. To investigate this result further, six cross
      linked polyethylene prostheses were taken and soaked in the serum lubricant at 37
      degrees C. Three of the prostheses were statically loaded and the other three
      were unloaded. These tests lasted for over one hundred and sixty days. It was
      found that the lubricant uptake of the unloaded control components was greater
      than that of the loaded com-ponents. The test with statically loaded prostheses
      was repeated, firstly with distilled water and then in lubricant heated to 30
      degrees C and 40 degrees C. No significant difference in weight increase due to
      lubricant uptake at these two temperatures was found. The weight increase due to
      soaking in dilute bovine serum was several times that due to soaking in distilled
      water. (Journal of Ap-plied Biomaterials & Biomechanics 2004; 2: 136-42).

PMID- 20803431
TI  - In vitro and in vivo follow-up of titanium transmucosal implants with a zirconia
      collar.
AB  - The advantages of transmucosal healing implants with a bioactive zirconia collar
      as a support for partially fixed prosthodontic restorations are optimal peri
      implant marginal tissue sealing, reduction in plaque accumulation and
      satisfactory aesthetic results. The zirconia used in this study evidenced not
      only optimal clinical performances, but also good biocompatibility. The results
      from this study demonstrated that zirconia coating enhances fibroblasts and
      osteoblast-like cell adhesion, spreading and proliferation, favoring microscopic
      tissue/cell in-growth and clinical implant fixation improvement. From clinical
      analysis, it emerged that the treatment group obtained better scores in every
      peri-implant parameter. This evidence attests faster stabilization of soft and
      hard tissues around both the transmucosal zirconia collar and at the crestal
      level of the implant. A reduced plaque accumulation around the implant with
      zirconia collar could provide a better peri-implant microbiological en-vironment
      by allowing the soft tissues expression of optimal sealing and good bone
      adaptation to loading. From these clinical and radiographic comparative analyzes,
      it emerged that in the treatment group the mean values were always similarly low.
      A rapid stabilization of both hard and soft peri-implant tissues was documented
      in the 1st yr. In the treatment group, there was the formation of stable tissue
      sealing the zirconia collar, which could preserve mucosal and bone levels. In
      conclusion, 2-yr clin-ical results demonstrated that implants supporting fixed
      restorations using transmucosal healing implants with a zirconia collar appeared
      a valid method, reporting 100% implant survival rates. Moreover, in vivo results
      obtained using strict parame-ters to assess the peri-implant status affirmed that
      a zirconia collar offers excellent biological acceptance. Our preliminary in
      vitro results statistically evidenced increased fibroblast and osteoblast
      adhesion and proliferation to zirconia compared to tita-nium, and an index of
      enhanced material integration with bone and soft tissue cells. (Journal of
      Applied Biomaterials & Biomechanics 2004; 2: 143-50).

PMID- 20803432
TI  - Inhibition of Ni release from NiTi and NiTiCu orthodontic archwires by nitrogen
      diffusion treatment.
AB  - The effects of nickel (Ni) allergy from NiTi alloys were reduced due to the
      titanium nitrided coating obtained by nitrogen gas diffusion at different
      temperatures. The samples were immersed in artificial saliva at 37 degrees C for
      different periods demonstrating that the titanium nitride coating prevents
      biodegradation. In addition, the lack of low friction coefficient for the NiTi
      super-elastic archwires makes the optimal use of these materials in orthodontic
      applications difficult. In this study, the reduction in this friction coefficient
      was achieved by nitrogen diffusion heat treatments. (Journal of Applied
      Biomaterials & Biomechanics 2004; 2: 151-5).

PMID- 20803433
TI  - Mechanical and ultrastructural evaluation of quartz post-endodontic
      reconstructions.
AB  - Aesthetics is a very important element in dentistry, but requires the support of
      good mechanical performance. Quartz fiber used in post-endodontic reconstruction
      is an aesthetic material, although there is little research concerning its
      mechanical properties. This study evaluated the retentive property of post
      endodontic reconstruction, composed of a quartz fiber post. Different thermal
      stresses were applied in vitro to post-endodontic reconstructions, in order to
      simulate oral thermal action on post-system dental structure linkage. We chose 30
      human extracted teeth, endodontically treated and restored, and then divided them
      into three groups of 10 teeth. A different treatment was applied to each group
      before mechanical testing: in the 1st group no treatment was done (controls); in
      the 2nd group teeth were subjected, in a climatic chamber, to 10 thermo-cycles
      between 4 degrees C and 58 degrees C; in the 3rd group teeth were stored in a
      saline solution at 37 degrees C for 48 hr. The teeth then underwent tensile shear
      stress tests at break point using a computerized electronic dynamometer. After
      mechanical testing, two teeth from each group were longitudinally half-sectioned,
      sputter-coated in gold and observed by scanning electron microscopy (SEM). The
      extracted quartz fiber post of each tooth also underwent SEM observation.
      Mechanical test results demonstrated that thermal cyclic variations could affect
      bond stability between dental structures and posts in quartz fiber
      reconstructions, whereas their bond strength seemed unaffected by humidity
      increases. Quartz fiber post SEM observation demonstrated a homogeneous structure
      and a regular fiber disposition. Dental root canal morphology SEM images always
      showed a different thickness in the cement layer. (Journal of Applied
      Biomaterials & Biomechanics 2004; 2: 156-61).

PMID- 20803434
TI  - In vitro biocompatibility of duplex stainless steel with and without 0.2%
      niobium.
AB  - Stainless steel is frequently used as a biomaterial. Chemical composition
      alterations can be undertaken to improve its mechanical and biological
      properties. This investigation aimed to compare the biocompatibility of duplex
      stainless steel, with and without 0.2% niobium, with austenitic stainless steel
      and titanium-6-aluminium-4-vanadium (Ti6Al4V) using rat bone marrow (RBM) cell
      culture. Cell attachment was evaluated at 24 hr. Cell proliferation, cell
      viability, total protein content, and alkaline phosphatase (ALP) activity were
      evaluated at 7, 14 and 21 days. Bone-like nodule formation was evaluated at 21
      days. Cell attachment, proliferation and viability were unaffected by the
      chemical composition of the stainless steels and the Ti6Al4V. Total protein
      content, ALP activity, and bone-like nodule formation were unaffected by the
      chemical composition of the stainless steels, but these parameters were greater
      on the Ti6Al4V than on the stainless steels. Our results demonstrated that
      initial cell events were unaffected by the chemical composition of the tested
      alloys, while events indicating osteoblast differentiation including increased
      ALP activity and bone-like nodule formation were favored by the Ti6Al4V.
      Moreover, the evaluated parameters were unaffected by the presence of niobium in
      the stainless steel composition. As niobium affects microstructure and,
      consequently, improves the mechanical properties of duplex stainless steel, it is
      suggested that the addition of niobium to metallic alloys could be useful in
      developing alloys with acceptable biocompatibility and improved mechanical
      features. (Journal of Applied Biomaterials & Biomechanics 2004; 2: 162-8).

PMID- 20803435
TI  - The adhesion of Flow 2002 fibroblasts to titanium implant materials is influenced
      by different surface topographies and is related to the immunocytochemical
      expression of fibronectin.
AB  - Osteointegrated titanium dental implants are widely used biomaterials that have
      to integrate within the alveolar bone and interact with periodontal soft tissues.
      In this study, we investigated the immunocytochemical expression of the extra
      cellular matrix (ECM) protein fibronectin (FN) and type I collagen (Coll I) in
      Flow 2002 fibroblast cultures spread on grade III-titanium samples with five
      different surface topographies and we correlated the immunocytochemical data to
      the adhesion capability of these cells to the above-mentioned substrates. Five
      different surfaces of grade III-titanium implants were at first characterized
      both by scanning electron microscopy (SEM) and by laser profilometry for surface
      roughness evaluation. After being spread on the biomaterial surfaces, the
      fibroblasts were left to proliferate for 72 hr and subsequently the cells
      underwent immunocytochemical procedures for detecting both FN and Coll I. The
      fibroblasts appeared more adherent to smoother titanium surfaces than to rougher
      ones; however, the highest cell density was detected on the roughest surface,
      even if it was unrelated to the highest FN expression. In the other biomaterial
      surfaces examined, as well as in controls, immunocytochemical FN expression
      correlated effectively to cell density on the examined substratum, whereas no
      determinant information was available regarding Coll I. It is reasonable to
      assume that surface roughness could be a relevant parameter influencing
      fibroblast adhesion to substrata; however, the evaluation of the cell density
      only is insufficient, and should be supported by the immunocytochemical FN
      expression, which could be confirmed as a useful tool in determining implant
      material biocompatibility. (Journal of Applied Biomaterials & Biomechanics 2004;
      2: 169-76).

PMID- 20803436
TI  - Pressure drop vs flow relationship in isolated preterm lamb tracheae.
AB  - Knowledge of immature tracheae mechanical behavior is fundamental in
      understanding the effects exerted on the upper airways by tidal liquid
      ventilation (TLV). Particularly, negative pressure can take place along the
      airways during expiration, which can cause airway collapse and flow limitation;
      therefore, representing a critical issue in preterm infant patients, whose
      airways are less stiff than adult ones. In this study, we investigated the
      expiratory pressure drop vs flow relationship of isolated preterm lamb tracheal
      samples to determine their hydraulic resistance, collapse pressure and collapse
      flow rate; a liquid flow through the samples was obtained by applying negative
      pressure at the outlet (cephalad) extremity of the tra-cheal sample, while
      keeping the inlet (caudal) extremity at atmospheric pressure. Histological
      analyzes were performed on the tracheal samples after each test session, in order
      to examine the morphological structure of the tracheal wall. Flow resistance
      tests demonstrated progressive lumen narrowing at increasing pressure drop
      (&#8710;P=P in -P out ). The flow rate increased with &#8710;P un-til a plateau
      was reached, and then decreased, describing the onset of a collapse phenomenon;
      however, complete occlusion was not reached. The tracheal samples demonstrated a
      similar behavior to that of a Starling resistor during the collapse phase: when a
      critical &#8710;P was reached, collapse was observed starting at the outlet
      region, which was subjected to the greatest negative pressure, then propagating
      towards the caudal direction. (Journal of Applied Biomaterials & Biomechanics
      2004; 2: 177-82).

PMID- 20803437
TI  - Surface modification of hydrogel intraocular lenses to prevent cell
      proliferation.
AB  - Intraocular lenses made from a hydrogel matrix were coated with a bioactive
      polymer exhibiting sulfonate and carboxylate groups. The anchorage of the
      macromolecular chains bearing the anionic groups to the hydrogel implant surface
      was obtained by an intermolecular reaction of the photosensitive groups attached
      to the ionic polymer, in order to obtain a pseudo-interpenetrated network. Cell
      proliferation assays performed on coated and uncoated hydrogel lenses showed an
      inhibiting effect of the bioactive polymer coating by up to 40% at day 6. The
      inhibiting effect was due to the presence and the distribution of both sulfonate
      and carboxylate groups along the macromolecular chains, which led to the
      appearance of ""bioactive sites"" allowing controlled interactions of surface,
      adhesive proteins and cells. (Journal of Applied Biomaterials & Biomechanics
      2004; 2: 183-9).

PMID- 20803438
TI  - "Biomaterials: from design to applications" - Selected short papers from SIB-GIB
      2004 Italian National Congress - 11-13 October 2004, Pisa - Italy.

PMID- 20803439
TI  - Coralline hydroxyapatite bone graft substitute: A review of experimental studies
      and biomedical applications.
AB  - A review of the various coral bone graft substitutes currently available for
      experimental and biomedical applications and ongoing investigations of coral
      derived bone replacement materials is presented here. Natural and synthetic graft
      materials that have been studied in vitro and in vivo and used in different
      medical procedures in osseous tissue have focused mainly on freeze-dried bone,
      hydroxyapatite (HA), tricalcium phosphate (TCP) and coral. Coralline
      hydroxyapatite (CHA) is manufactured from marine coral, which has a natural
      trabecular structure similar to that of bone, by the hydrothermal conversion of
      the calcium carbonate skeleton of coral to hydroxyapatite, a calcium phosphate.
      While many studies have demonstrated promising biocompatible properties and
      osteogenic results, as a bone graft substitute and bone void filler, the use of
      CHA may be limited owing to its inherent mechanical weakness and reduced
      biodegradation. The benefits of CHA as bone graft are predominantly its safety,
      biocompatibility and osteoconductivity so that it can be used as a substitution
      biomaterial for bone in many indications clinically. CHA can also be used as an
      efficient carrier system for the local delivery of growth factors to enhance
      osteointegration and implant fixation into peri-implant osseous tissue.

PMID- 20803440
TI  - Hydroxyapatite nanoparticles: A review of preparation methodologies.
AB  - Hydroxyapatite (HA) has been widely used as a biocompatible ceramic in many areas
      of medicine, but mainly for contact with bone tissue, due to its resemblance to
      mineral bone. In mammals, the skeleton presents a carbonated and partially
      substituted apatite, based on nanocrystal aggregates, and associated with
      collagen, building up 3-D structures present in various bone tissue conformations
      like trabecular or cancellous bone. There has been growing interest in developing
      bioactive synthetic ceramics that could closely mimic natural apatite
      characteristics. This review presents some of the most well known forms of
      obtaining, by precipitation methods, nanophased HA. Some traditional and more
      recent developments vis-a-vis the pos-sible HA nanoparticles applications are
      discussed.

PMID- 20803441
TI  - Alpha-Tricalcium phosphate-gelatin composite cements.
AB  - This study investigates gelatin influence on calcium phosphate cement (CPC)
      setting properties. Cements of different compositions were prepared using |Alpha 
      tricalcium phosphate (|Alpha -TCP) enriched with a small amount of dicalcium
      phosphate dihydrate (DCPD), and different gelatin amounts up to 20 wt%. The
      cements, prepared with a liquid/powder ratio of 0.3 ml/g, were soaked in
      simulated body fluid (SBF) for different times inverted exclamation markU21 days.
      The setting reaction of the control cement prepared without gelatin occurred in 7
      days, whereas the transformation of the cements at high gelatin content into
      apatite was almost complete in 2-day aging in SBF. Gelatin presence reduced the
      total porosity of the cements, and significantly modified their microstructure.
      The fractured surface of the aged control cement was covered with entangled plate
      like apatite crystals, whereas the gelatin cements displayed more compact
      surfaces, most likely due to the inhibiting effect of gelatin on apatite crystal
      growth. The microstructural modifications were in agreement with the mprovement
      of the mechanical properties in the aged cements, the compressive strength of
      which increased linearly as a function of gelatin content, from 2.0 inverted
      exclamation markA 0.8 to 14 inverted exclamation markA 1 MPa.

PMID- 20803442
TI  - Immediate implant placement using injectable calcium phosphate hydraulic cement
      in dogs.
AB  - Techniques allowing implant placement in extraction sockets require either high
      diameter implants in surgically enlarged sockets or grafting and/or regenerative
      procedures around implants after their primary surgical stabilization. This study
      aimed to evaluate the ability of calcium phosphate hydraulic cement (CPHC) to
      immobilize commercially available titanium implants in extraction sockets. CPHC
      was used in seven fresh dog extraction sockets in conjunction with ITI TPS
      implants. Three extraction sockets without CPHC were used as controls. Initial
      implant stability was measured after 10 min hardening with periostest. The dogs
      were sacrificed after 9 months. Non-decalcified specimens were prepared for
      histologic and histomor-phometric examination. The surface percentage of implant
      to-mineralized bone contact and bone density was calculated for each specimen.
      The periotest values were significantly different for implants stabilized with
      CPHC than for the controls, and simi-lar to values reported for osteointegrated
      implants. New alveolar bone was formed in intimate contact with titanium. In two
      cases, non-resorbed CPHC residues were observed closely bound to the implant.
      This study clearly demonstrates that CPHC cement is suitable for immediate
      implant immobilization in extraction sockets.

PMID- 20803444
TI  - Removal of viruscide agents by using styrenic resins.
AB  - Strong and weak anionic polystyrene/divinylbenzene ion exchange resins were
      investigated both as iodophores and as iodine/iodide ion removal agents in blood
      disinfection applications. Resin-iodine complexes were prepared, but there was no
      significant iodine release observed in either distilled water or isotonic saline
      solution. However, all ion-exchange resin were able to remove almost
      quantitatively both iodine and iodide ions from water solutions. Cross-linked
      styrene/divinylbenzene resins are excellent polyaromatic viruscide adsorbents,
      although their hydrophobicity is responsible for poor wettability in physiologi
      cal fluids. Surface modification with hydrophilic reagents appeared a promising
      strategy to overcome this drawback. A Merrifield-type chloromethylated resin and
      a highly cross-linked mesoporous resin (Lewatit 1064) with a large surface area
      and content of unreacted vinyl groups were selected as starting materials. The
      Merrifield resin was modified by the reaction of the pendant chloromethyl groups
      with triethyleneglycol, tetraethyleneglycol and a -cyclodextrin. The conversion
      of Lewatit double bonds into hydrophilic moieties was attempted by the radical
      grafting of N-vinyl-2-pyrrolidinone (NVP), maleic anhydride (MAn), 2-hydroxyethyl
      methacrylate, acrylamide (AAm) and different poly(ethyleneglycol) (PEG)
      methacrylates. The addition of 2-mer-captoethanol (2ME) and epoxidation were also
      investigated. The modified Merrifield resins demonstrated very low efficiency in
      acridine viruscide uptake, in spite of the large increase in both wettability and
      water uptake. On the other hand, all modified Lewatit samples removed rapidly and
      almost quantitatively the viruscide from aqueous solutions, although only a few
      samples resulted in being very hydrophilic. In all cases, hydrophilicity and
      viruscide adsorbing capacity were maintained after heating at 180 degrees C to
      simulate pyrogen elimination.

PMID- 20803443
TI  - The novel use of waste animal bone from New Zealand agricultural sources as a
      feedstock for forming plasma sprayed hydroxyapatite coatings on biomedical
      implant materials.
AB  - This study presents the feasibility of using animal bone-derived hydroxyapatite
      (HAP) as feedstock powders for plasma spraying. Bovine, cervine and ovine bone
      from abattoirs was boiled in a pressure cooker to remove blood, fat and adhering
      meat tissue. The bone was then placed in a muffler furnace, pyrolyzed at
      approximately 1000 degrees C to remove collagen and resid-ual organics, cooled
      and subsequently ground to a powder then digested in nitric acid. Sodium
      hydroxide was added to the digest to reprecipitate the HAP. Ageing of the
      precipitate followed by filtration, extensive washing and drying produced the
      white powder used as the feedstock. X-ray diffractometry (XRD) and Fourier
      transform infrared spectroscopy (FTIR) confirmed the powder to be poorly
      crystalline HAP with low-level carbonate. Out of several batches of the sieved
      powders, one batch was plasma sprayed to produce adherent HAP coatings;
      therefore, demonstrating that animal bone-derived HAP powders can be seri-ously
      considered as a feedstock powder, subject to the powder being processed for the
      correct rheological characteristics for easy flowing within the plasma spray flow
      lines. The phase composition of the successful plasma sprayed HAP coatings on
      both stainless steel and titanium were found by XRD to be mainly HAP with minor
      contributions from a -tricalcium phosphate, tetra-calcium phosphate and CaO;
      therefore, demonstrating that feedstock decomposition on its passage through the
      plasma spray torch was insignificant under the conditions employed. Scanning
      electron microscopy (SEM) micrographs of the coatings indicated that their
      morphology featured the classical heterogeneous and splat-like appearance
      expected of plasma sprayed coatings. Young's modulus and Vicker's microhardness
      tests conducted on the coatings revealed values in the range, respectively, 22-87
      GPa and 166-287 (HV200 ) indicating high strength plasma spray HAP coatings had
      been produced from the feedstock powder.

PMID- 20803445
TI  - Bone response to zinalco implants.
AB  - The evolution of dog femur bone implanted in vivo with either steel or with a
      metal alloy (zinalco), was compared at different time-periods inverted
      exclamation markU9 months. Bone behavior was studied by radiology, scanning
      electron microscopy (SEM), thermo-gravimetric analysis (TGA) and Fourier
      transform infrared spectroscopy (FTIR) and it was shown that zinalco corroded
      whereas the steel remained unaltered in the presence of body fluids. Small
      amounts of metal ions were released continuously, promoting disordered bone
      growth enriched with organic tissue. After 9 months, the organism managed to
      compensate for this effect and the proportion of mineral to organic tissue
      resulted in being normal, although it was unable to correct the shape and the
      direction of the growth.

PMID- 20803446
TI  - Protein interaction with hydrogel contact lenses.
AB  - The first event observed at the interface between a contact lens and tear fluid
      is protein adsorption. Tears have a rich and complex composition, allowing a wide
      range of interactions and competitive processes. The majority of studies avail
      able on protein adsorption have focused on blood/plasma/serum protein on solid
      surfaces. However, recently the interaction of tear proteins with contact lenses
      has become an important field of research following the widespread use of contact
      lenses in many physiological and pathological conditions. Protein adsorption on
      contact lenses is the overall result of various types of in-teractions between
      the different components present, i.e. the chemical composition and the surface
      charge, the structure of the protein molecules, the nature of the medium (tears)
      and many other solutes present in tears. The chemical structure of contact lenses
      and their physical and biological behavior are considered, followed by tear film
      structure and biochemistry. Finally, the nature and mechanism of protein
      adsorption on contact lenses, factors affecting adsorption and attempts to reduce
      protein ad-sorption are reviewed. (Journal of Applied Biomaterials & Biomechanics
      2004; 2: 1-19).

PMID- 20803448
TI  - Wear studies of all UHMWPE couples under various bio-tribological conditions.
AB  - Wear tests were undertaken in which ultra high molecular weight polyethylene
      (UHMWPE) was rubbed against itself. Tests primarily employed a pin-on-plate wear
      test machine, with distilled water, Ringer solution and dilute bovine serum being
      used as the lubricants. Loads of 10N and 40N were employed, and some test pins
      had a rotational motion added. In all cases wear was high, with mean wear factors
      of up to 91 10 -6 mm3/Nm being measured, but the addition of rotation reduced the
      amount of material worn from the test plates. In the presence of bovine serum and
      under reciprocation only, pin wear was relatively low. With bovine serum as the
      lubricant, total mean wear factors for the UHMWPE couples were calculated to be
      in the range of 35 to 58 10-6mm3/Nm. Therefore the pin-on-plate tests showed that
      the choice of lubricant as well as the motion applied to the test pin had a
      significant influence on the wear volumes measured. A two-piece UHMWPE
      'prosthesis' with matching hemispherical faces was fabricated and tested on a
      finger simulator. Distilled water was used as the lubricant and wear factors were
      found to be greater for the metacarpal component, 21 10 -6mm3/Nm, than the
      phalangeal component, 3 10-6mm3/Nm, after ten million cycles of testing. This
      result paralleled the greater wear seen by the plate than by the pin in the pin
      on-plate tests under reciprocating motion. (Journal of Applied Biomaterials &
      Biomechanics 2004; 2: 29-34).

PMID- 20803447
TI  - Influence of heat treatment on structural, mechanical and wear properties of
      crosslinked UHMWPE.
AB  - New crosslinked ultra high molecular weight polyethylenes (UHMWPEs) have recently
      been developed, characterized and introduced in clinical applications. UHMWPE
      cross-linking treatments are very promising for reducing osteolysis induced by
      wear debris. The irradiation type, gamma or beta, the dosage and the thermal
      treatment performed during or following the irradiation process are all factors
      affecting polyethylene wear resistance. Thermal stabilization treatments
      performed after or during the irradiation process at a temperature above melting
      point (i.e. >130 degrees C) have been proven to effectively remove the free
      radicals generated during irradiation from UHMWPE, but their effect on the
      mechanical properties of UHMWPE are not completely clear. In addition to wear
      rate reduction, maintaining good mechanical properties is fundamental aspect in
      designing the new generation of crosslinked UHMWPE for artificial load bearing
      materials, especially considering the application in total knee replacements. In
      this study, we investigated the influence of different stabilization treatments,
      performed after gamma irradiation, on structural, wear and mechanical properties
      of UHMWPE. We performed four different stabilization treatments, with different
      temperatures and cooling rates, on 100 kGy gamma irradiated UHMWPE. Structural
      properties of UHMWPE were assessed by differential scanning calorimetry (DSC). To
      assess the mechanical performance of the materials, uni-axial tensile tests were
      performed according to the ASTM D638 standard, bi-axial tension performance was
      evaluated by small punch tests (ASTM F2183-02), toughness resistance was
      evaluated by the Izod method (ASTM F648), and cold flow resistance was analysed
      by a dynamic compressive test. Evaluation of wear resistance was by a
      multidirectional pin-on-disk screening machine. Materials considered were in
      ""aged"" and ""non-aged"" conditions. Results confirmed that cross-linking
      greatly enhances UHMWPE wear resistance, but introduces some detrimental effects
      on the mechanical properties. In this study, we found that the negative ef-fects
      on the mechanical properties of crosslinked UHMWPE can be modulated, to some
      extent, by choosing a thermal stabiliza-tion treatment at a correct temperature
      and cooling rate. (Journal of Applied Biomaterials & Biomechanics 2004; 2: 20-8).

PMID- 20803450
TI  - Finite element analysis of a knee joint replacement during a gait cycle.
AB  - A three-dimensional (3-D) computer model was developed to predict,
      simultaneously, the knee joint replacement motions and the stresses occurring
      within the tibial insert under complex loading conditions. Friction contacts,
      polyethylene elastic- plastic behavior and soft tissue restraints were
      considered. Finite element analysis of the entire gait cycle was performed
      applying the displacement and loading conditions reported in the draft ISO 14243
      1. The 3-D model was used to predict contact stresses and areas occurring within
      the polyethylene insert, when static loads of single instants on the gait cycle
      were applied. Results at 13% and 46% of the gait cycle were calculated with both
      entire cycle sim-ulation and single instant simulations. The predicted peak
      contact stress and contact area values were greater for single in-stant analyzes
      (respectively, 21% and 9%) if compared with those of the entire cycle simulation.
      In addition, single instant simulations were unable to predict accurately the
      contact region location, which was displaced in the anterior direction. Two
      different configurations of soft tissue restraints were compared; the first
      adopted from the draft ISO 14243-1 and the second from literature data. There
      were no significant differences observed between the two configurations. In
      particular, peak contact stresses followed the same trend, although the
      restraints of the literature data provided lower values in the last phase of the
      gait cycle. A preliminary verification of model reliability was performed
      comparing the tibial insert motions with data reported in the literature, under
      simplified loading conditions applied to the femoral component. (Journal of
      Applied Biomaterials & Biomechanics 2004; 2: 45-54).

PMID- 20803449
TI  - Titanium for osteointegration: Comparison between a novel biomimetic treatment
      and commercially exploited surfaces.
AB  - The objective of this preliminary in vitro biological study was to assess the
      effect of the surface physicochemical and topographical properties of a novel
      bioactive titanium (BSP) obtained by BioSpark treatment. A short-term study was
      per-formed to evaluate the bone cell response to BSP and compare it to two
      commercially available materials: no treated (TI) and chemically etched (ETC)
      titanium. Material characterization was carried out using scanning electron
      microscopy (SEM), energy dispersion spectroscopy (EDS), non-contact laser
      profilometry (LPM), and Thin Film X-ray Diffraction (TF-XRD). Surface analysis
      showed ETC to have the highest rough surface, followed by TI surface and then BSP
      being the smoothest material at micro level, but showing a sub micrometer porous
      structure covered with a ""net-like"" rough structure. The BSP surface was found
      to consist of a layer of amorphous calcium and phosphorus and crystalline
      titanium oxide, not detected in the other materials tested. Indirect biological
      cytotoxicity studies were performed to determine cell viability following
      incubation with the eluted extract of the materials. Results indicated no
      remarkable deterioration in cell viability. In particular, no detectable effect
      was observed on cellular viability as a result of the chemical interaction
      between the BSP bioactive surface and the surrounding culture medium. Direct
      cellular studies showed that the material surface resulted in good cell adhesion
      on BSP samples. This could be related to both the nano-roughness, and also the
      crystallinity of the superficial layer of titanium oxide coupled with bioactive
      Ca- and P-chemical enrichment. The cellular proliferation analysis demonstrated a
      remarkably higher activity for the cells cultured on BSP, with values
      significantly higher than the other test materials and the control for all time
      points. These findings are highly suggestive that the surface properties of the
      BioSpark treated titanium significantly increases cell proliferation rate. In
      conclusion, this study has demonstrated that the novel bioactive treatment shows
      potential as a method for improving osteointegration properties of titanium for
      orthopaedic and dental implants. (Journal of Applied Biomaterials & Biomechanics
      2004; 2: 35-44).

PMID- 20803451
TI  - A comparative evaluation of chondrocyte/scaffold constructs for cartilage tissue
      engineering.
AB  - This study aimed to evaluate three biodegradable scaffolds as cell carriers for
      in vitro cartilage regeneration using mature human chondrocyte cells. We compared
      cell distribution, viability and morphology and we evaluated the mechanical
      properties of the constructs after 2 weeks of in vitro culture. The materials
      used as scaffolds were fibrin glue, a collagen sponge and a polyurethane foam
      (DegraPol(R)). Fibrin glue was found unsuitable as a chondrocyte carrier vehicle
      after culture times longer than a few days, probably due to significant barriers
      to nutrients and oxygen diffusion, and the material weakened rapidly. The
      collagen-based sponge was found to be unsuitable to support chondrocyte survival
      in vitro, although the presence of newly synthesized collagen was observed in
      these constructs. The synthetic biodegradable scaffold was more adequate in
      supporting cell survival and mechanical properties. After 2 weeks of static
      culture, the storage modulus obtained by dynamic shear testing was in the order
      of 0.7 kPa in fibrin constructs, 3.7 kPa in collagen constructs and 105 kPa in
      DegraPol(R) constructs. The better mechanical stability of the synthetic foam
      supports further investigation in the possible use of synthetic biomaterials as
      biodegradable scaffolds for in vitro cartilage regeneration. (Journal of Applied
      Biomaterials & Biomechanics 2004; 2: 55-64).

PMID- 20803452
TI  - In vitro and in vivo tests for the biological evaluation of candidate orthopedic
      materials: Benefits and limits.
AB  - The development of reliable experimental models for the clinical use of
      biomaterials and in predicting implant success or failure is becoming
      increasingly important in attaining adequate health and safety conditions. This
      paper summarizes the main benefits and limits of in vitro and in vivo biological
      tests taking into account general pathophysiological considerations regarding the
      skeletal tissue. Current findings demonstrate the need to adopt both in vitro and
      in vivo methodologies and to improve test quality with particular attention to
      the ethical issues associated with in vivo experiments. (Journal of Applied
      Biomaterials & Biomechanics 2003; 1: 155-63).

PMID- 20803453
TI  - N+ ion implantation of Ti6Al4V alloy and UHMWPE for total joint replacement
      application.
AB  - Multidirectional pin-on-plate tribological wear tests were performed to evaluate
      and compare the tribological behavior of N+ ion-implanted and unmodified
      Ti6Al4V/ultra high molecular weight polyethylene (UHMWPE) sliding couples, for
      total joint replacement (TJR) applications. Knoop microhardness indentations were
      measured and an increase in surface hardness of more than twofold and up to four
      times, respectively, was observed for the Ti6Al4V alloy and UHMWPE after N+ ion
      implantation, at a load of 1 gf. Increase in hardness was attributed to the
      formation of TiN precipitates and cross-linking in the alloy and polymer,
      respectively. Wear test results showed that N+ ion implantation reduced surface
      wear of the Ti6Al4V alloy and, in turn, significantly reduced the wear of the
      mating UHMWPE. Atomic force microscopy (AFM), X-ray photoelectron spectroscopy
      (XPS), scanning electron microscopy (SEM), non-contacting interferometry and
      optical microscopy were used to characterize both modified and unmodified
      material surfaces prior to and after tribological wear tests. The results
      indicated that N+ ion-implanted Ti6Al4V/UHMWPE sliding couples were distinctly
      superior to the unmodified sliding couples, and demonstrated a definite potential
      for the use of N+ ion-implanted Ti6Al4V and implanted UHMWPE as load bearing
      surfaces in TJR prostheses. (Journal of Applied Biomaterials & Biomechanics 2003;
      1:164-71).

PMID- 20803454
TI  - Porous titanium obtained by a new powder metallurgy technique: Preliminary
      results of human osteoblast adhesion on surface polished substrates.
AB  - This study concerns a novel powder metallurgy method for producing porous
      titanium (pTi) exhibiting high mechanical properties. The preparation procedure
      consisted of the following stages: first, the preparation of Ti and titanium
      hydride (TiH2) powder mixtures and their consolidation with a cold isostatic
      press, followed by a sintering of the green bodies performed with hot isostatic
      press (HIP) equipment. Thermal decomposition in controlled environment of the
      TiH2 phase results in the foam structure. The resulting porosity percolates with
      a volume fraction of approximately 20%. The final material exhibits interesting
      mechanical properties, comparable to those of full density titanium (between
      grade 2 and grade 3), with the advantage of a minor density. The samples produced
      were tested to verify their biological response by studying the effectiveness of
      osteoblast adhesion and growth. In this preliminary study, osteoblastic cell
      morphology was investigated and compared to that observed on fully dense
      commercially pure titanium (Ti-cp) (ASTM, grade 3). The preliminary results were
      promising regarding cellular adhesion and spreading. (Journal of Applied
      Biomaterials & Biomechanics 2003; 1: 172-7).

PMID- 20803455
TI  - Bioactive polymers grafted on silicone to prevent Staphylococcus aureus
      prosthesis adherence: in vitro and in vivo studies.
AB  - As joint prostheses become infected preventive strategies are needed. Silicone
      prostheses were coated with a COO - and SO3 - bearing bioactive copolymer, Q5,
      synthesized by radical polymerization and the adherence of Staphylococcus aureus
      (S. aureus)to them was evaluated in vitro and in vivo. Copolymer Q5 contains
      tris(trimethylsiloxy) methacryloxy propyl silane favoring the compatibility with
      the silicone matrix, cinnamoyl ethyl methacrylate allowing a network formation at
      the surface of the silicone prostheses, two ionic monomers: methacrylic acid and
      sodium styrene sulfonate. In vitro experiments were conducted on Q5-coated
      silicone lenses and on Q5-coated silicone prostheses. In both cases, materials
      were incubated with fi-bronectin (Fn) because of its important role in S. aureus
      adherence to implant surfaces. The percentage of adhesion inhibition was observed
      at approximately 40% for the coated materials compared to the untreated silicone.
      Rabbits underwent double-blind partial knee replacements with Q5-coated or
      control implants fitted into the intramedullary canal of the tibia, and 10 7
      bacteria were injected into the knees. The number of bacteria adherent on the
      prostheses was determined 24 hr later. Signifi-cantly fewer bacteria adhered to
      Q5-coated than control prostheses (2.26 +/- 0.76 vs 3.86 +/- 0.54 log10 CFU/ml; p
      < 0.0035). Bioactive polymer coating could provide a new method of preventing
      joint-prosthesis infections. (Journal of Applied Biomaterials & Biomechanics
      2003; 1: 178-85).

PMID- 20803456
TI  - Injectable calcium phosphate hydraulic cement (CPHC) used for periodontal tissue
      regeneration: A study of a dog model.
AB  - Injectable calcium phosphate hydraulic cement (CPHC) is a new bone substitute
      family. This study aimed to evaluate the use of CPHC in surgical periodontitis
      simulating defects in a dog model. CPHC was obtained by adding powder mixtures of
      different calcium phosphates with different solubility. Alveolar bone was removed
      by drilling over the mesial and distal roots of the 2nd mandibular premolar in
      six dogs. The defects were randomly selected, three were untreated and six
      treated. The defects had a depth of 6 mm and a width of 3 mm. The animals were
      sacrificed after 9 months and samples prepared, with no decalcification, for
      histological evaluation. Seventy-nine percent of the root was covered by bone in
      the experimental defects, compared to 41% of the root for the control defects.
      Bone height was significantly higher for the experimental defects (4.9 +/- 0.9
      mm) than for the control defects (1.4 +/- 0.5 mm). After 9 months, 97 +/- 6% of
      the CPHC was degradated and replaced by bone. This study proves the interest of
      this cement because of the particularly high level of periodontal bone
      regeneration. The ability of the cement to be easily injected and shaped in bone
      defects and the immediate immobilization of the teeth after hardening is notable.
      (Journal of Applied Biomaterials & Biomechanics 2003; 1: 186-93).

PMID- 20803457
TI  - Skull biomechanics: The energy absorbability of the human skull frontal bone
      during fracture under quasi-static loading.
AB  - Four human skulls were studied in order to determine the energy absorbed
      corresponding to a fracture due to quasi-static loading on the frontal bone.
      Using a dedicated experimental set up, the force-deformation characteristics of
      the specimens were recorded, calculating energy absorption. Mean values of 1975
      +/- 703 N, 4.17 +/- 0.81 mm and 3.95 +/- 1.18 J were found for the peak force,
      maximum deformation and absorbed energy to fracture, respectively. Linear
      fractures were always seen in the frontal bone, with a similar pattern in three
      of the four skulls. These results can be used to develop bench-mark skull models
      to validate analytic models. (Journal of Applied Biomaterials & Biomechanics
      2003; 1: 194-9).

PMID- 20803458
TI  - Precipitation of carbonateapatite from a revised simulated body fluid in the
      presence of glucose.
AB  - Revised simulated body fluid (rSBF) was modified by the addition of glucose in a
      physiological amount. The influence of this compound on calcium phosphate
      crystallization from supersaturated solutions equal to 4 x rSBF ionic
      concentrations was studied under physiological conditions (solution pH=7.35-7.40,
      temperature 37.0 +/- 0.5 degrees C). The experiments were performed in both
      plastic vessels (fast-uncontrolled precipitation) and in a constant-composition
      double-diffusion (CCDD) device (slow precipitation under strictly controlled
      conditions). Solutions used had different concentrations of hydrogencarbonate
      ions and with or without Hepes buffer. Regardless of the experimental conditions
      chosen, glucose was found to have a negligible influence on calcium phosphate
      crystallization from rSBF, while hydrogencarbonate ions had a strong influence on
      the structure and chemical composition of the precipitates. (Journal of Applied
      Biomaterials & Biomechanics 2003; 1: 200-7).

PMID- 20803459
TI  - Selected short papers from SIB-GIB 2003 Italian National Congress.

PMID- 20803460
TI  - Osteointegration of titanium and its alloys by anodic spark deposition and other
      electrochemical techniques: a review.

PMID- 20803461
TI  - Properties of THFMA-PEMA and BMA-PEMA-based bone cements characterized by thermal
      analysis, FTIR and NMR.

PMID- 20803462
TI  - Biological evaluation of the effects of the surface roughness and composition of
      titanium discs on an immortalized human osteoblastic cell line.

PMID- 20803463
TI  - Expression of activation antigens and adhesion molecules on mononuclear cells
      after short contact with materials for intraocular lenses.

PMID- 20803464
TI  - The effect of composition, wettability and roughness of the substrate on in vivo
      early bacterial colonization of titanium.

PMID- 20803465
TI  - A biomechanical comparison of three plating techniques for fracture of the
      humerus.

PMID- 20803466
TI  - Influence of specimen molding technique on fatigue properties of a bone cement.

PMID- 20803467
TI  - Foreword.

PMID- 20803469
TI  - Alumina and zirconia ceramics in joint replacements.
AB  - Ceramic biomaterials have gained widespread use in arthroprostheses joints.
      Ceramic oxides including alumina as a -corundum Al2 O3 and zirconia, as yttria
      stabilised zirconia polycrystals, were used in large number of patients,
      especially in the manufacture of ball heads for hip replacements. The experience
      and the feedbacks gathered in more than 30-year clinical use of alumina, and 15
      year use of zirconia are reviewed. The results of in vitro and in vivo studies on
      the biocompatibility of alumina and zirconia ceramics are analyzed as well as the
      studies on carcinogenicity. (Journal of Applied Biomaterials & Biomechanics 2003;
      1: 19-32).

PMID- 20803468
TI  - Composite materials for biomedical applications: a review.
AB  - The word ""composite"" refers to the combination, on a macroscopic scale, of two
      or more materials, different for composition, morphology and general physical
      properties. In many cases, and depending on the constituent properties,
      composites can be designed with a view to produce materials with properties
      tailored to fulfill specific chemical, physical or mechanical requirements.
      Therefore over the past 40 years the use of composites has progressively
      increased, and today composite materials have many different applications, i.e.,
      aeronautic, automotive, naval, and so on. Consequently many composite
      biomaterials have recently been studied and tested for medical application. Some
      of them are currently commercialized for their advantages over traditional
      materials. Most human tissues such as bones, tendons, skin, ligaments, teeth,
      etc., are composites, made up of single constituents whose amount, distribution,
      morphology and properties determine the final behavior of the resulting tissue or
      organ. Man-made composites can, to some extent, be used to make prostheses able
      to mimic these biological tissues, to match their mechanical behavior and to
      restore the mechanical functions of the damaged tissue. Different types of
      composites that are already in use or are being investigated for various
      biomedical applications are presented in this paper. Specific advantages and
      critical issues of using composite biomaterials are also described (Journal of
      Applied Bio-materials & Biomechanics 2003; 1: 3-18).

PMID- 20803470
TI  - A novel biomimetic treatment for an improved osteointegration of titanium.
AB  - Direct osteointegration of titanium and titanium alloys implants is one of the
      main goals of biomaterials research for dental and orthopedic applications.
      Chemical, mechanical or biological treatments are investigated searching for fast
      and durable implant to bone bonding. The aim of the present work is to assess the
      in vitro mineralisation capabilities and to investigate the mechanical and
      physico-chemical properties of a new biomimetic treatment on titanium. The new
      surface treatment was obtained using Anodic Spark Deposition technique, and
      consists of a first ASD treatment performed in solutions containing phosphate
      ions followed by a second ASD treatment in a solution rich in calcium ions. The
      resulting surface is finally treated by alkali etching. The physio-chemical and
      mechanical properties of this material are analyzed and the mineralization
      potential is considered by surface analysis after soaking it in different
      solutions of simulated body fluid (SBF). The developed biomimetic treatment was
      then compared to other treatments from the literature. The proposed treatment was
      found to possess a very high mineralization capaci-ty, that makes its application
      very interesting in terms of speed and strength of direct implant
      osteointegration. (Journal of Ap-plied Biomaterials & Biomechanics 2003; 1: 33
      42).

PMID- 20803471
TI  - Cyclic deformation fatigue behaviour of Ti6Al4V thermochemically nitrided for
      articular prostheses.
AB  - Titanium and its alloys have many attractive properties including high specific
      strength, low density, and excellent corrosion resistance. Titanium and the
      Ti6Al4V alloy have long been recognized as materials with high biocompatibility.
      These properties have led to the use of these materials in biomedical
      applications. Despite these advantages, the lack of good wear resistance makes
      the use of titanium and Ti6Al4V difficult in some biomedical applications, for
      example, articulating components of prostheses. To overcome this limitation,
      nitriding has been investigated as a surface-hardening method for titanium.
      Although nitriding greatly improves the wear resistance, this method reduces the
      fatigue strength. Low cycle fatigue performance in air of nitrided Ti6Al4V at
      different deformation amplitudes has been studied. Results show a reduction of
      low cycle fatigue life of up to 10% compared to the non-treated material. Studies
      suggest it is not related to the titanium nitride surface layer, but to
      microstructural changes caused by the high temperature treatment. (Journal of
      Applied Biomaterial & Biomechanics 2003; 1: 43-7).

PMID- 20803472
TI  - Partially resorbable acrylic bone cements based on self-curing acrylic/phosphate
      glass formulations.
AB  - Partially resorbable self-curing cements based on poly(methyl
      methacrylate)/phosphate glasses were prepared by mixing methyl methacrylate
      monomer with poly(methyl methacrylate) powder in different proportions (20-60 wt
      %) of phosphate glass (BV11) in the system 44.5-P2 O5 , 44.5-CaO, 11-Na2 O (mol
      %). The curing of these formulations showed a reduction of 10 degrees C in the
      maximum temperature and an increase of 10 minutes in the setting time although
      the content of residual monomer in the cured materials was unaltered. The
      presence of the inorganic particles did not significantly change the glass
      transition temperature of the cement. Static mechanical properties were evaluated
      in compression. The compressive yield strength of PM-MA/BV11 cements were in the
      range 110-118 MPa, superior to those of the control for dry specimens. When the
      test was conducted with wet specimens, a decrease in strength was observed due to
      the dissolution of the glasses in the medium, but the composites prepared with 20
      or 40 wt-% BV11 had the compressive yield strengths required by the international
      standard for acrylic bone cements (ISO 5833). The dynamic mechanical properties
      of the formulation containing 60 wt-% BV11 and the corresponding control were
      evaluated through a fatigue crack propagation test. The results showed that both
      formulations followed a Paris-Erdogan model in the stable crack propagation, with
      no significant differences in the value of the exponent m of the mentioned law.
      Finally, the presence of the phosphate glasses in the acrylic composite did not
      change the wear damage of the pair UHMWPE/Ti6Al4V produced by the PMMA
      formulations. (Journal of Applied Biomaterials & Biomechanics 2003; 1: 48-57).

PMID- 20803473
TI  - Cytocompatibility of polyurethane foams as biointegrable matrices for the
      preparation of scaffolds for bone reconstruction.
AB  - This work reports preliminary results on the development of biointegrable
      scaffolds, composed of biostable 3D polymer matrices and bioabsorbable inorganic
      salts, to be used for cell anchorage in bone regeneration. Three crosslinked
      polyurethane foams (PUFs), prepared by one-step bulk polymerisation from a
      polyether-polyol mixture, polymeric MDI and water as expanding agent, were tested
      for their ability to promote adhesion and growth of bone-derived cells. The open
      porosity of these foams ranged from 16 to 31% with an average pore size of 470
      /600 microm, compressive strength (at 10% &#949; ) of 0.28/0.38 MPa and elastic
      moduli of 4.88/6.61 MPa. The human osteosarcoma line Saos-2, and primary cultures
      of normal human articular chondrocytes and bone marrow-derived (HBM) stromal
      cells were used for in vitro cytocompatibility tests. For cell adhesion and
      proliferation analysis, DNA synthesis was evaluated by 3 H-thymidine uptake.
      Osteoblastic differentiation of Saos-2 adherent cells was determined by measuring
      the enzymatic activity of alkaline phosphatase (ALP). All cell types were able to
      adhere to all tested PUFs and to synthesize DNA. At 48 hr culture, HBM stromal
      cells showed the maximal rate of adhesion with the highest rate of proliferation
      onto PUFs with the largest pore size, whereas both chondrocytes and Saos-2
      appeared to adhere preferentially onto foams exhibiting the highest percentage of
      open porosity. Up to 8 days in culture Saos-2 cells were able to proliferate into
      all PUFs, with a time-dependent increase of DNA synthesis and ALP activity. At
      SEM, the morphology of cells adherent to PUF pores was spread with cytoplasmatic
      extroflessions, indicating a good metabolic activation. These results demonstrate
      a good cytocompatibility of the proposed 3D matrices, suggesting that their use
      in the preparation of composite scaffolds is worth further investigation.
      (Journal of Applied Biomaterials & Biomechanics 2003; 1: 58-66)ABSTRACT: This
      work reports preliminary results on the development of biointegrable scaffolds,
      composed of biostable 3D polymer matrices and bioabsorbable inorganic salts, to
      be used for cell anchorage in bone regeneration. Three crosslinked polyurethane
      foams (PUFs), prepared by one-step bulk polymerisation from a polyether-polyol
      mixture, polymeric MDI and water as expanding agent, were tested for their
      ability to promote adhesion and growth of bone-derived cells. The open porosity
      of these foams ranged from 16 to 31% with an average pore size of 470 /600
      microm, compressive strength (at 10% &#949; ) of 0.28/0.38 MPa and elastic moduli
      of 4.88/6.61 MPa. The human osteosarcoma line Saos-2, and primary cultures of
      normal human articular chondrocytes and bone marrow-derived (HBM) stromal cells
      were used for in vitro cytocompatibility tests. For cell adhesion and
      proliferation analysis, DNA synthesis was evaluated by 3 H-thymidine uptake.
      Osteoblastic differentiation of Saos-2 adherent cells was determined by measuring
      the enzymatic activity of alkaline phosphatase (ALP). All cell types were able to
      adhere to all tested PUFs and to synthesize DNA. At 48 hr culture, HBM stromal
      cells showed the maximal rate of adhesion with the highest rate of proliferation
      onto PUFs with the largest pore size, whereas both chondrocytes and Saos-2
      appeared to adhere preferentially onto foams exhibiting the highest percentage of
      open porosity. Up to 8 days in culture Saos-2 cells were able to proliferate into
      all PUFs, with a time-dependent increase of DNA synthesis and ALP activity. At
      SEM, the morphology of cells adherent to PUF pores was spread with cytoplasmatic
      extroflessions, indicating a good metabolic activation. These results demonstrate
      a good cytocompatibility of the proposed 3D matrices, suggesting that their use
      in the preparation of composite scaffolds is worth further investigation.
      (Journal of Applied Biomaterials & Biomechanics 2003; 1: 58-66).

PMID- 20803474
TI  - Hydrothane(R) interactions with biological components: a comparison with
      Chronoflex(R).
AB  - The interaction of a glycol-containing polyurethane, Hydrothane(R), was assessed
      with respect to protein adsorption and cell and bacterial adhesion. The results
      obtained were compared with those from a second polyurethane, Chronoflex(R).
      Dynamic contact angle (DCA) and protein adsorption studies indicated that the
      overall hydrophilic nature of Hydrothane in physiological environment was
      affected by the possible presence of hydrophobic domains still exposed at the
      surface after wetting. Indeed, despite the high degree of hydrophilicity in an
      aqueous environment, a stronger protein binding was evidenced on Hydrothane when
      the two serum- and urine-conditioned polyurethane surfaces were selectively
      washed by isopropanol/water mixtures of increasing concentrations. Furthermore,
      immunoblotting of the serum proteins adsorbed on Hydrothane demonstrated the
      presence on its surface of proteins able to establish hydrophobic interactions
      such as human serum albumin (HSA) and a 1-microglobulin ( a 1-m). The C3 fragment
      of complement showed an immunoblotting profile different from the control serum
      suggesting an activation of this fragment. The adhesion of fibroblasts and
      Pseudomonas aeruginosa on the surface of the two materials was evaluated and the
      data were related to protein adsorption. In both cases Hydrothane showed levels
      of adhesion of eukaryotic and prokaryotic cells significantly lower than
      Chronoflex. These data were related to the absence of a significant binding of
      proteins such as fibronectin bringing amino acid receptor sequences in their
      structure. (Journal of Applied Biomaterials & Biomechanics 2003; 1: 67-75).

PMID- 20803475
TI  - Effects of total hip arthroplasty cemented femoral stem surface finish, collar
      and cement thickness on load transfer to the femur.
AB  - Stress shielding and load transfer to the femur following total hip arthroplasty
      have been studied extensively. A number of models have addressed the effects of
      surface finish of double-tapered, non-collared cemented stems on load transfer to
      the femur. However, a great number of cemented femoral stem designs in wide use
      today are not double tapered, and many, such as the Charnley, have collars. The
      effects of surface finish of such stems on load transfer to the femur are not
      completely understood. In this study, we measured the effects of surface finish
      of a straight, non-tapered cemented femoral stem, with and without a collar, in
      two stem sizes, on load transfer to the femur, using an in vitro laboratory
      model. Eight types of straight stems were fabricated, with polished or rough
      surfaces, with and without a collar, and in two sizes. All stems were based on
      the same template, and varied only in the desired combination of parameters
      studied. Three each of the eight unique stem types (total of 24 specimens) were
      cyclically loaded for 77,000 cycles at 1 Hz, alternating between walking and
      stair-climbing load profiles. Surface strains were measured at ten locations in
      each femur during designated initial and final periods. Of the three design
      variables, stem surface finish had the greatest effect on femoral surface
      strains. Specifically, compared to rough stems, with polished stems, mean
      proximal medial compressive strains were smaller, whereas mean distal medial
      compressive strains were greater. In contrast, on the anterior surface, mean
      proximal anterior tensile strains were greater, whereas mean distal anterior
      strains were smaller. All femoral surface strains increased with cyclic loading,
      however, strains increased at a greater rate with polished stems than with rough
      stems. Proximal medial strains were somewhat increased with the presence of a
      collar, however, these differences were small (< 100 microa ) and/or not
      statistically significant. Similarly, distal medial strains were increased with
      the presence of a collar but, again, the differences were not consistent (p >
      0.16). Compared to large stems, with small stems, proximal medial compressive
      strains were greater. The results emphasize the importance cemented femoral stem
      surface roughness and the manner in which this changes stem-cement bond strength,
      affecting the distribution of stresses in the femur. This is an important
      consideration in the design of femoral stems. (Journal of Applied Biomaterials &
      Biomechanics 2003; 1: 76-83).

PMID- 20803476
TI  - Effect of hyaluronan on calcification-nodule formation from human periodontal
      ligament cell culture.
AB  - The periodontal ligament (PDL) has been found to house progenitor elements which
      may give rise to a new periodontium when properly triggered. Complex molecular
      mechanisms are involved in guiding such cells towards their final regenerative
      task. Hyaluronan (HA), an extracellular matrix molecule abundantly present during
      early tissue development, is usually found at high concentrations in all adult
      mammalian PDL tissue. In this study, PDL cells were cultured on HA coated
      experimental plastic Petri's dishes (E.D.) and mineralized-nodules formation, at
      the microscopical level, was evaluated in comparison to HA-free control dishes
      (C.D.) after 21 days. Little colony formation occurred in presence of HA, whereas
      CD showed normal cell confluence with mineralization of nodules even at 10 days.
      However, when harvesting was performed from both dishes after only 12 hours,
      before cell aggregation occurred, cell confluence and nodule formation could be
      seen with no apparent difference between test and control. This study shows that,
      with respect to PDL cells, hyaluronan seems to inhibit cell adhesion, although
      with no interference with cell aggregates calcifying potentials. This latter
      finding may: a) provide further insight in analyzing the properties of
      extracellular matrix substrates in the PDL environment, b)guide research to
      possible explanations on how the PDL maintains its characteristics of uncalcified
      tissue and c) lead to theorize regarding utilization in tissue regeneration.
      (Journal of Applied Biomaterial & Biomechanics 2003; 1: 84-90).

PMID- 20803477
TI  - Characterization of protein release from hydrolytically degradable poly(ethylene
      glycol) hydrogels.
AB  - We present a novel fully hydrophilic, hydrolytically degradable poly(ethylene
      glycol) (PEG) hydrogel suitable for soft tissue engineering and delivery of
      protein drugs. The gels were designed to overcome drawbacks associated with
      current PEG hydrogels (i.e., reaction mechanisms or degradation products that
      compromise protein stability): the highly selective and mild cross-linking
      reaction allowed for encapsulating proteins prior to gelation without altering
      their secondary structure as shown by circular dichroism experiments. Further,
      hydrogel degradation and structure, represented by mesh size, were correlated to
      protein release. It was determined that polymer density had the most profound
      effect on protein diffusivity, followed by the polymer molecular weight, and
      finally by the specific chemical structure of the cross-linker. By examining the
      diffusion of several model proteins, we confirmed that the protein diffusivity
      was dependent on protein size as smaller proteins (e.g., lysozyme) diffused
      faster than larger proteins (e.g., Ig). Furthermore, we demonstrated that the
      protein physical state was preserved upon encapsulation and subsequent release
      from the PEG hydrogels and contained negligible aggregation or protein-polymer
      adducts. These initial studies indicate that the developed PEG hydrogels are
      suitable for release of stable proteins in drug delivery and tissue engineering
      applications.

PMID- 20803478
TI  - Genome-wide screen of Saccharomyces cerevisiae for killer toxin HM-1 resistance.
AB  - We screened a set of Saccharomyces cerevisiae deletion mutants for resistance to
      killer toxin HM-1, which kills susceptible yeasts through inhibiting 1,3-beta
      glucan synthase. By using HM-1 plate assay, we found that eight gene-deletion
      mutants had higher HM-1-resistance compared with the wild-type. Among these eight
      genes, five--ALG3, CAX4, MNS1, OST6 and YBL083C--were associated with N-glycan
      formation and maturation. The ALG3 gene has been shown before to be highly
      resistant to HM-1. The YBL083C gene may be a dubious open reading frame that
      overlaps partially the ALG3 gene. The deletion mutant of the MNS1 gene that
      encodes 1,2-alpha-mannosidase showed with a 13-fold higher HM-1 resistance
      compared with the wild-type. By HM-1 binding assay, the yeast plasma membrane
      fraction of alg3 and mns1 cells had less binding ability compared with wild-type
      cells. These results indicate that the presence of the terminal 1,3-alpha-linked
      mannose residue of the B-chain of the N-glycan structure is essential for
      interaction with HM-1. A deletion mutant of aquaglyceroporin Fps1p also showed
      increased HM-1 resistance. A deletion mutant of osmoregulatory mitogen-activated
      protein kinase Hog1p was more sensitive to HM-1, suggesting that high-osmolarity
      glycerol pathways plays an important role in the compensatory response to HM-1
      action.

PMID- 20803479
TI  - Metabolic regulation rather than de novo enzyme synthesis dominates the osmo
      adaptation of yeast.
AB  - Intracellular accumulation of glycerol is essential for yeast cells to survive
      hyperosmotic stress. Upon hyperosmotic stress the gene expression of enzymes in
      the glycerol pathway is strongly induced. Recently, however, it was shown that
      this gene-expression response is not essential for survival of an osmotic shock
      [Mettetal JT et al. (2008) Science 319: 482-484 and Westfall PJ et al. (2008)
      Proc Natl Acad Sci 105: 12212-12217]. Instead, pure metabolic adaptation can
      rescue the yeast. The existence of two alternative mechanisms urged the question
      which of these mechanisms dominates time-dependent adaptation of wild-type yeast
      to osmotic stress under physiological conditions. The regulation of the glycerol
      pathway was analysed in aerobic, glucose-limited cultures upon addition of 1 M of
      sorbitol, leading to a hyperosmotic shock. In agreement with earlier studies, the
      mRNA levels of the glycerol-producing enzymes as well as their catalytic
      capacities increased. Qualitatively this induction followed a similar time course
      to the increase of the glycerol flux. However, a quantitative regulation analysis
      of the data revealed an initial regulation by metabolism alone. After only a few
      minutes gene expression came into play, but even after an hour, 80% of the
      increase in the glycerol flux was explained by metabolic changes in the cell, and
      20% by induction of gene expression. This demonstrates that the novel metabolic
      mechanism is not just a secondary rescue mechanism, but the most important
      mechanism to regulate the glycerol flux under physiological conditions.

PMID- 20803480
TI  - Effects of yokukansan and donepezil on learning disturbance and aggressiveness
      induced by intracerebroventricular injection of amyloid beta protein in mice.
AB  - The effects of yokukansan and donepezil on learning disturbance and
      aggressiveness were examined in amyloid beta protein (Abeta)-injected mice.
      Intellicage tests showed that both yokukansan and donepezil ameliorated Abeta
      induced learning disturbance, but the ameliorating effect of donepezil was not
      enhanced by concomitant administration of yokukansan. On the other hand, a social
      interaction test showed that Abeta-induced aggressiveness was ameliorated by
      yokukansan, but not by donepezil. Co-administration of both drugs also
      ameliorated aggressiveness, as did yokukansan alone. In vitro binding assays
      revealed that yokukansan did not bind to choline receptors or transporters. In
      vitro enzyme assays revealed that yokukansan did not affect choline
      acetyltransferase activity or inhibit acetylcholinesterase activity, as did
      donepezil. These results suggest that yokukansan might ameliorate aggressiveness
      without interfering with the pharmacological efficacy (antidementia effect) of
      donepezil and also that concomitant administration of yokukansan might be useful
      for amelioration of aggressiveness, which was not lessened by donepezil. The
      difference in the efficacies of both drugs may be due to a difference in their
      pharmacological mechanisms.

PMID- 20803481
TI  - Structure elucidation of new acacic acid-type saponins from Albizia coriaria.
AB  - Three new acacic acid derivatives, named coriariosides C, D, and E (1-3) were
      isolated from the roots of Albizia coriaria. Their structures were elucidated on
      the basis of extensive 1D- and 2D-NMR studies and mass spectrometry as 3-O-[beta
      D-xylopyranosyl-(1 -> 2)-beta-D-fucopyranosyl-(1 -> 6)-2-(acetamido)-2-deoxy-beta
      D-glucopyranosyl]-21-O-{(2E,6S)-6-O-{4-O-[(2E,6S)-2,6-dimethyl- 6-O-(beta-D
      quinovopyranosyl)octa-2,7-dienoyl]-4-O-[(2E,6S)-2,6-dimethyl-6-O-(beta-D
      quinovopyranosyl)octa-2,7-dienoyl]-beta-D-quinovopyranosyl}-2,6-dimethylocta-2,7
      dienoyl}acacic acid 28-O-beta-D-xylopyranosyl-(1 -> 4)-alpha-L-rhamnopyranosyl-(1
      -> 2)-beta-D-glucopyranosyl ester (1), 3-O-{beta-D-fucopyranosyl-(1 -> 6)-[beta-D
      glucopyranosyl-(1 -> 2)]-beta-D-glucopyranosyl}-21-O-{(2E,6S)-6-O-{4-O-[(2E,6S)
      2,6-dimethyl-6-O-(beta-D-quinovopyranosyl)octa-2,7-dienoyl]-4-O-[(2E,6S)-2,6
      dimethyl-6-O-(beta-D-quinovopyranosyl)octa-2,7-dienoyl]-beta-D-quinovopyranosyl}
      2,6-dimethylocta-2,7-dienoyl}acacic acid 28-O-alpha-L-rhamno pyranosyl-(1 -> 2)
      beta-D-glucopyranosyl ester (2), and 3-O-[beta-D-fucopyranosyl-(1 -> 6)-beta-D
      glucopyranosyl]-21-O-{(2E,6S)-6-O-{4-O-[(2E,6S)-2,6-dimethyl-6-O-(beta-D
      quinovopyranosyl)octa-2,7-dienoyl)-beta-D-quinovopyranosyl]octa-2,7
      dienoyl}acacic acid 28-O-beta-D-glucopyranosyl ester (3).

PMID- 20803482
TI  - Links between analysis of surrogate endpoints and endogeneity.
AB  - There has been substantive interest in the assessment of surrogate endpoints in
      medical research. These are measures that could potentially replace 'true'
      endpoints in clinical trials and lead to studies that require less follow-up.
      Recent research in the area has focused on assessments using causal inference
      frameworks. Beginning with a simple model for associating the surrogate and true
      endpoints in the population, we approach the problem as one of endogenous
      covariates. An instrumental variables estimator and general two-stage algorithm
      are proposed. Existing surrogacy frameworks are then evaluated in the context of
      the model. In addition, we define an extended relative effect estimator as well
      as a sensitivity analysis for assessing what we term the treatment
      instrumentality assumption. A numerical example is used to illustrate the
      methodology.

PMID- 20803484
TI  - Changes in bone fatigue resistance due to collagen degradation.
AB  - Clinical tools for evaluating fracture risk, such as dual energy X-ray
      absorptiometry (DXA) and quantitative ultrasound (QUS), focus on bone mineral and
      cannot detect changes in the collagen matrix that affect bone mechanical
      properties. However, the mechanical response tissue analyzer (MRTA) directly
      measures a whole bone mechanical property. The aims of our study were to
      investigate the changes in fatigue resistance after collagen degradation and to
      determine if clinical tools can detect changes in bone mechanical properties due
      to fatigue. Male and female emu tibiae were endocortically treated with 1 M KOH
      for 1-14 days and then either fatigued to failure or fatigued to induce stiffness
      loss without fracture. Partial fatigue testing caused a decrease in modulus
      measured by mechanical testing even when not treated with KOH, which was detected
      by MRTA. At high stresses, only KOH-treated samples had a lower fatigue
      resistance compared to untreated bones for both sexes. No differences were
      observed in fatigue behavior at low stresses for all groups. KOH treatment is
      hypothesized to have changed the collagen structure in situ and adversely
      affected the bone. Cyclic creep may be an important mechanism in the fast
      deterioration rate of KOH-treated bones, as creep is the major cause of fatigue
      failure for bones loaded at high stresses. Therefore, collagen degradation caused
      by KOH treatment may be responsible for the observed altered fatigue behavior at
      high stresses, since collagen is responsible for the creep behavior in bone.

PMID- 20803485
TI  - Time-dependent density functional theory study on the absorption spectrum of
      Coumarin 102 and its hydrogen-bonded complexes.
AB  - The effect of both solvent polarity and hydrogen bonding (HB) on the electronic
      transition energy of Coumarin 102 (C102) has been examined using the time
      dependent density functional theory (TDDFT). Solvent effect on both geometry and
      electronic transition energy is evaluated using the polarizable continuum model
      (PCM). A linear relation of the absorption maximum of C102 with the solvent
      polarity function Deltaf is found using the TDDFT-PCM method for all solvents
      except dimethyl sulfoxide. The solvent polarity and the type B HB between the
      carbonyl oxygen and solvent hydrogen atom make the absorption wavelength
      redshift, whereas the type A HB between the amino nitrogen atom and solvent
      hydrogen atom has an opposite effect on the absorption wavelength. The calculated
      absorption wavelengths of C102 with two type B HB between the carbonyl oxygen and
      solvent hydrogen atom are in excellent agreement with experimental measurements.
      The solvatochromism of C102 is analyzed in terms of the Kamlet-Taft equation and
      the parameters s and a are discussed.

PMID- 20803483
TI  - Effects of botulinum toxin-induced paralysis on postnatal development of the
      supraspinatus muscle.
AB  - The mechanical environment plays an important role in musculoskeletal tissue
      development. The present study characterized changes in supraspinatus muscle due
      to removal of mechanical cues during postnatal development. An intramuscular
      injection of botulinum toxin type A (BTX) was used to induce and maintain
      paralysis in the left shoulders of mice since birth while the right shoulders
      received saline and served as contralateral controls. A separate group of animals
      was allowed to develop normally without any injections. Muscles were examined
      postnatally at various time points. The maximum isometric tetanic force generated
      by the muscle was significantly reduced in the BTX group compared to saline and
      normal groups. The paralyzed muscles were smaller and showed significant muscle
      atrophy and fat accumulation on histologic evaluation. Myogenic genes myogenin,
      myoD1, myf5, myf6, and fast type II myosin heavy chain (MHC) isoform were
      significantly upregulated while slow type I MHC isoform was significantly
      downregulated in the BTX group. Adipogenic genes C/EBPalpha, PPARgamma2, leptin,
      and lipoprotein lipase were significantly upregulated in the BTX group. Results
      indicate that reduced muscle loading secondary to BTX-induced paralysis leads to
      fat accumulation and muscle degeneration in the developing muscle. Understanding
      the molecular and compositional changes in developing supraspinatus muscles may
      be useful for identifying and addressing the pathological changes that occur in
      shoulder injuries such as neonatal brachial plexus palsy.

PMID- 20803487
TI  - Performance of 3D-space-based atoms-in-molecules methods for electronic
      delocalization aromaticity indices.
AB  - Several definitions of an atom in a molecule (AIM) in three-dimensional (3D)
      space, including both fuzzy and disjoint domains, are used to calculate electron
      sharing indices (ESI) and related electronic aromaticity measures, namely,
      I(ring) and multicenter indices (MCI), for a wide set of cyclic planar aromatic
      and nonaromatic molecules of different ring size. The results obtained using the
      recent iterative Hirshfeld scheme are compared with those derived from the
      classical Hirshfeld method and from Bader's quantum theory of atoms in molecules.
      For bonded atoms, all methods yield ESI values in very good agreement, especially
      for C-C interactions. In the case of nonbonded interactions, there are relevant
      deviations, particularly between fuzzy and QTAIM schemes. These discrepancies
      directly translate into significant differences in the values and the trends of
      the aromaticity indices. In particular, the chemically expected trends are more
      consistently found when using disjoint domains. Careful examination of the
      underlying effects reveals the different reasons why the aromaticity indices
      investigated give the expected results for binary divisions of 3D space.

PMID- 20803486
TI  - Cement-related particles interact with proinflammatory IL-8 chemokine from human
      primary oropharyngeal mucosa cells and human epithelial lung cancer cell line
      A549.
AB  - Epidemiological studies have shown that respirable exposure to emitted cement
      particulate matter is associated with adverse health risk for human. The
      underlying mechanisms, however, are poorly understood. To examine the effect of
      cement, nine blinded cement-related particulates (<10 MUm) were assessed with
      regard to their induction of the proinflammatory cytokines IL-6 and IL-8 in human
      primary epithelial cells (pEC) from oropharyngeal mucosa as well as from nonsmall
      cell lung carcinoma (non-SCLC) cells A549. It was demonstrated that the cement
      specimens did not act cytotoxic as assessed by the lactate dehydrogenase (LDH)
      assay. The basal and IL-1beta-induced IL-8 expression was suppressed, in contrast
      to an unchanged IL-6. At the transcript level the basal and induced IL-6 and IL-8
      gene expression was not influenced by cement dust. To discover the mechanism by
      which cement influenced the IL-8 expression the following experiments were
      performed. Submerse exposure experiments have shown that the release of IL-8 was
      suppressed by cement dust. Furthermore, the incubation of IL-8 with cement
      related specimens under cell-free condition led to a loss of immunoreactive IL-8.
      An immunological masking of IL-8 by free soluble components of respiratory
      epithelial cells was excluded. Thus, the decrease of IL-8 protein content after
      cement exposure seems to be a result of the adsorption of IL-8 protein to cement
      particles and the inhibition of IL-8 release. In conclusion, due to absent
      cytotoxic and inflammatory effects of cement-related specimens in both human pEC
      and A549 cell models it remains open how cement exposure may lead to the
      respiratory adverse effects in humans.

PMID- 20803488
TI  - NMR quantification using an artificial signal.
AB  - We have developed QUANTAS (QUANTification by Artificial Signal), which is a
      software-based protocol for concentration measurement by NMR. QUANTAS is an
      absolute intensity external standard method for quantification by NMR that
      compensates for various experimental parameters. It is applicable to all nuclei
      and modern spectrometers. QUANTAS is demonstrated here for (1)H and (19)F NMR,
      enabling heteronuclear integrals to be compared. It can be applied using fixed
      probe tuning, matching and pulse length, for samples with the same effective
      loading on the probe coil as the appropriate reference spectrum. Otherwise, an
      optimised tuning and matching approach is adopted for every sample together with
      explicit PULCON (PUlse Length-based CONcentration measurements) absolute
      intensity corrections.

PMID- 20803489
TI  - Re: Effect of quercetin on bone formation: JOR 25:1061-1066, 2008 and other
      publications reporting the effects of various materials on bone formation in
      rabbit calvarial defects.

PMID- 20803490
TI  - First molecules, biological chirality, origin(s) of life.
AB  - Origin(s) of biological chirality appear(s) to be intimately connected to
      origin(s) of life. Prebiotic evolution toward these important turning points can
      be traced back to single chiral molecules. These can be small (monomeric) units
      as amino acids or monosaccharides or oligomers as oligo-RNA type molecules.
      Earlier speculations about these two kinds of entries to biological chirality are
      critically reviewed.

PMID- 20803491
TI  - Enhanced chromatographic NMR with polyethyleneglycol. A novel resolving agent for
      diffusion ordered spectroscopy.
AB  - NMR analysis of complex mixtures can be significantly simplified using
      polyethyleneglycol (PEG) as resolving additive in DOSY NMR technique, which
      allows the extraction of individual spectra of mixture components with differing
      polarity. Resolving power of PEG-assisted DOSY was demonstrated with natural
      product mixtures.

PMID- 20803493
TI  - Indirect detection of the 183W and 57Fe nuclei using 119Sn-relayed 1H,X
      correlation spectroscopy.
AB  - Recently reported triple-resonance Y-relayed (1)H,X correlation experiments have
      been utilized to characterize (183)W and (57)Fe chemical shifts using (119)Sn as
      the Y-relaying nucleus instead of the previously used (31)P. Application of an
      adaptation of Gudat's original INEPT/HMQC sequence results in a significant
      enhancement of the signal-to-noise (S/N) ratio for two-dimensional (119)Sn
      relayed (1)H,(183)W and (1)H, (57)Fe correlation spectra with efficient detection
      of the transition metal nucleus in tungsten and iron complexes lacking an
      observable direct scalar coupling between the transition metal and any hydrogen
      nuclei. Strengths and shortcomings of the novel sequence and the original
      sequences reported by Gudat are discussed in the context of (119)Sn-relayed
      proton detection of very low frequency transition metal nuclei.

PMID- 20803492
TI  - Estimating chromatographic enantioselectivity (alpha) from gradient
      enantioselective chromatography data.
AB  - Calculation of chromatographic enantioselectivity (alpha) is critically important
      in enantioselective chromatographic method development studies. The fact that
      alpha can only be calculated from isocratic elution conditions, whereas gradient
      elution conditions are predominantly used in method development screening,
      presents some problems for the use of alpha as a scoring indicator for automated,
      intelligent enantioselective chromatography method development systems. In this
      study, an empirical algorithm was developed to estimate alpha at isocratic
      conditions based upon information collected from a gradient elution. The
      algorithm was validated for SFC applications and has been shown to accurately
      predict enantioselectivity for a wide variety of racemic test analytes eluted on
      different chiral column and mobile phase conditions.

PMID- 20803494
TI  - A simple chromatographic route for the isolation of meso diaminopimelic acid.
AB  - Meso diaminopimelic acid is an important noncoded amino acid found in Gram
      negative bacterial peptidoglycan. In spite of its importance, this stereoisomer
      is not available commercially. A simple, economical procedure was developed for
      the isolation of pure meso diaminopimelic acid via an high-performance liquid
      chromatography separation. In our new approach, the underivatized three isomers
      of diaminopimelic acid were separated on a crown ether-based chiral stationary
      phase. For the structure identification, (1)H NMR spectroscopy was applied.

PMID- 20803496
TI  - Mechanical resolution of chiral objects in achiral media: where is the size
      limit?
AB  - Macroscopic chiral objects (boats and planes with turned rudders, shoes, etc.)
      get separated from their mirror-image counterparts by motion in achiral media.
      However, chiral molecules are not enantio-differentiated without the presence of
      a chiral environment, which may be due to other chiral molecules in the medium.
      This article explores the reasons of this micro/macro difference as well as the
      size borderline between the two regimes. There are two major demarcation lines,
      both related to the object's chaotic thermal motion. The first one is due to
      destruction of the necessary spatial orientation by the fast rotational
      diffusion. Only particles larger than 1 MUm can maintain their original
      orientation for 1 sec or longer. For smaller particles, an additional external
      orienting factor, e.g., a strong electric field has to be applied. The second
      limitation is defined by the ratio of the hydrodynamic separation of the
      enantiomers (which is directly proportional to time) to their displacement due to
      the translational Brownian motion (which is proportional to square root of time).
      On the laboratory time scales (up to a year), the chiral objects have to be
      larger than 0.25 MUm to be resolved. On evolutionary time scales, much smaller
      object could be resolved. For enantiomers approaching the molecular size, periods
      comparable to the age of the universe would be required.

PMID- 20803495
TI  - Enantioselective pharmacokinetics of (R)- and (S)-ketamine after a 5-day infusion
      in patients with complex regional pain syndrome.
AB  - INTRODUCTION: This study determined the pharmacokinetics and pharmacodynamics of
      (R)- and (S)-ketamine and (R)- and (S)-norketamine following a 5-day moderate
      dose, as a continuous (R,S)-ketamine infusion in complex regional pain syndrome
      (CRPS) patients. MATERIALS AND METHODS: Ketamine was titrated to 10-40 mg/h and
      maintained for 5 days. (R)- and (S)-Ketamine and (R)- and (S)-norketamine
      pharmacokinetic and pharmacodynamic studies were performed. Blood samples were
      obtained on Day 1 preinfusion, and at 60-90, 120-150, 180-210, and 240-300 min
      after the start of the infusion, on Days 2, 3, 4, 5, and on Day 5 at 60 min after
      the end of infusion. The plasma concentrations of (R)- and (S)-ketamine and (R)-
      and (S)-norketamine were determined using enantioselective liquid chromatography
      mass spectrometry. RESULTS: Ketamine and norketamine levels stabilized 5 h after
      the start of the infusion. (R)-Ketamine clearance was significantly lower
      resulting in higher steady-state plasma concentrations than (S)-ketamine. The
      first-order elimination for (S)-norketamine was significantly greater than that
      of (R)-enantiomer. When comparing the pharmacokinetic parameters of the patients
      who responded to ketamine treatment with those who did not, no differences were
      observed in ketamine clearance and the first-order elimination of norketamine.
      CONCLUSION: The results indicate that (R)- and (S)-ketamine and (R)- and (S)
      norketamine plasma concentrations do not explain the antinociceptive activity of
      the drug in patients suffering from CRPS.

PMID- 20803498
TI  - Root-mean-square-deviation-based rapid backbone resonance assignments in
      proteins.
AB  - We have shown that the methodology based on the estimation of root-mean-square
      deviation (RMSD) between two sets of chemical shifts is very useful to rapidly
      assign the spectral signatures of (1)H(N), (13)C(alpha), (13)C(beta), (13)C',
      (1)H(alpha) and (15)N spins of a given protein in one state from the knowledge of
      its resonance assignments in a different state, without resorting to routine
      established procedures (manual and automated). We demonstrate the utility of this
      methodology to rapidly assign the 3D spectra of a metal-binding protein in its
      holo-state from the knowledge of its assignments in apo-state, the spectra of a
      protein in its paramagnetic state from the knowledge of its assignments in
      diamagnetic state and, finally, the spectra of a mutant protein from the
      knowledge of the chemical shifts of the corresponding wild-type protein. The
      underlying assumption of this methodology is that, it is impossible for any two
      amino acid residues in a given protein to have all the six chemical shifts
      degenerate and that the protein under consideration does not undergo large
      conformational changes in going from one conformational state to another. The
      methodology has been tested using experimental data on three proteins, M
      crystallin (8.5 kDa, predominantly beta-sheet, for apo- to holo-state), Calbindin
      (7.5 kDa, predominantly alpha-helical, for diamagnetic to paramagnetic state and
      apo to holo) and EhCaBP1 (14.3 kDa, alpha-helical, the wild-type protein with one
      of its mutant). In all the cases, the extent of assignment is found to be greater
      than 85%.

PMID- 20803500
TI  - Development of neurons on micropatterns reveals that growth cone responds to a
      sharp change of concentration of laminin.
AB  - In this report we fabricated laminin (LN) stripes on a background of poly-L
      lysine as substrates for the growth of rat hippocampal neurons, and found that a
      sharp change of the concentration of LN guides the growth of neurites by leading
      the growth cones in a time- and space-dependent manner. The percentage of
      neurites that grow along the edge of LN stripes (where there is a sharp change of
      concentration) decreases as a function of the concentration of LN under a
      threshold value. The actin cytoskeleton plays an important role in the process of
      growth cone's response to the sharp change of concentration of LN on
      micropatterns. We believe that the findings here are useful for not only
      fundamental studies in neuroscience, but also helpful for the design of devices
      or chips for nervous prosthesis.

PMID- 20803499
TI  - A common variant in the patatin-like phospholipase 3 gene (PNPLA3) is associated
      with fatty liver disease in obese children and adolescents.
AB  - The genetic factors associated with susceptibility to nonalcoholic fatty liver
      disease (NAFLD) in pediatric obesity remain largely unknown. Recently, a
      nonsynonymous single-nucleotide polymorphism (rs738409), in the patatin-like
      phospholipase 3 gene (PNPLA3) has been associated with hepatic steatosis in
      adults. In a multiethnic group of 85 obese youths, we genotyped the PNLPA3 single
      nucleotide polymorphism, measured hepatic fat content by magnetic resonance
      imaging and insulin sensitivity by the insulin clamp. Because PNPLA3 might affect
      adipogenesis/lipogenesis, we explored the putative association with the
      distribution of adipose cell size and the expression of some adipogenic/lipogenic
      genes in a subset of subjects who underwent a subcutaneous fat biopsy. Steatosis
      was present in 41% of Caucasians, 23% of African Americans, and 66% of Hispanics.
      The frequency of PNPLA3(rs738409) G allele was 0.324 in Caucasians, 0.183 in
      African Americans, and 0.483 in Hispanics. The prevalence of the G allele was
      higher in subjects showing hepatic steatosis. Surprisingly, subjects carrying the
      G allele showed comparable hepatic glucose production rates, peripheral glucose
      disposal rate, and glycerol turnover as the CC homozygotes. Carriers of the G
      allele showed smaller adipocytes than those with CC genotype (P = 0.005).
      Although the expression of PNPLA3, PNPLA2, PPARgamma2(peroxisome proliferator
      activated receptor gamma 2), SREBP1c(sterol regulatory element binding protein
      1c), and ACACA(acetyl coenzyme A carboxylase) was not different between
      genotypes, carriers of the G allele showed lower leptin (LEP)(P = 0.03) and
      sirtuin 1 (SIRT1) expression (P = 0.04). CONCLUSION: A common variant of the
      PNPLA3 gene confers susceptibility to hepatic steatosis in obese youths without
      increasing the level of hepatic and peripheral insulin resistance. The rs738409
      PNPLA3 G allele is associated with morphological changes in adipocyte cell size.

PMID- 20803501
TI  - Management of the diffusion of 4-methylumbelliferone across phases in
      microdroplet-based systems for in vitro protein evolution.
AB  - Fluorongenic reagents based on 4-methylumbelliferone (4-MU) have been widely used
      for the detection of phosphatase, sulfatase, esterase, lipase and glycosidase
      activities in conventionally formatted enzyme assay systems. However, the
      sensitivity of assays based on these substrates is also potentially very useful
      in the microdroplet formats now being developed for high throughput in vitro
      evolution experiments. In this article, we report the investigation of diffusion
      of 4-MU as a model dye from water-in-oil droplets and the internal aqueous phase
      of water-in-oil-in-water droplets in microfluidics. The effect of BSA in the
      aqueous phase on the diffusion of 4-MU is also discussed. Based on these results,
      we provided here proof-of-concept of the reaction of the enzyme OpdA with the
      substrate coumaphos in water-in-oil-in-water droplets. In this double-emulsion
      system, the reaction of OpdA and coumaphos was achieved by allowing coumaphos to
      diffuse from the continuous aqueous phase across the oil phase into the internal
      aqueous droplets.

PMID- 20803502
TI  - Electroporation of micro-droplet encapsulated HeLa cells in oil phase.
AB  - Electroporation (EP) is a method widely used to introduce foreign genes, drugs or
      dyes into cells by permeabilizing the plasma membrane with an external electric
      field. A variety of microfluidic EP devices have been reported so far. However,
      further integration of prior and posterior EP processes turns out to be very
      complicated, mainly due to the difficulty of developing an efficient method for
      precise manipulation of cells in microfluidics. In this study, by means of a T
      junction structure within a delicate microfluidic device, we encapsulated HeLa
      cells in micro-droplet of poration medium in oil phase before EP, which has two
      advantages: (i) precise control of cell-encapsulating droplets in oil phase is
      much easier than the control of cell populations or individuals in aqueous
      buffers; (ii) this can minimize the electrochemical reactions on the electrodes.
      Finally, we successfully introduced fluorescent dyes into the micro-droplet
      encapsulated HeLa cells in oil phase. Our results reflected a novel way to
      realize the integrated biomicrofluidic system for EP.

PMID- 20803503
TI  - How to measure the transmetallation of a gadolinium complex.
AB  - The suitability of paramagnetic complexes as contrast agents depends not only on
      their relaxivity but also on their stability and inertness towards
      transmetallation processes by endogenous ions. In this work, we describe a
      convenient method to study the stability of paramagnetic Gd complexes through the
      evolution of the paramagnetic longitudinal relaxation rate of water protons at 37
      degrees C.

PMID- 20803504
TI  - Somatic mutations and the hierarchy of hematopoiesis.
AB  - Clonal disease is often regarded as almost synonymous with cancer. However, it is
      becoming increasingly clear that our bodies harbor numerous mutant clones that
      are not tumors, and mostly give rise to no disease at all. Here we discuss three
      somatic mutations arising within the hematopoietic system: BCR-ABL,
      characteristic of chronic myeloid leukemia; mutations of the PIG-A gene,
      characteristic of paroxysmal nocturnal hemoglobinuria; the V617F mutation in the
      JAK2 gene, characteristic of myeloproliferative diseases. The population
      frequencies of these three blood disorders fit well with a hierarchical model of
      hematopoiesis. The fate of any mutant clone will depend on the target cell and on
      the fitness advantage, if any, that the mutation confers on the cell. In general,
      we can expect that only a mutation in a hematopoietic stem cell will give long
      term disease; the same mutation taking place in a cell located more downstream
      may produce just a ripple in the hematopoietic ocean.

PMID- 20803505
TI  - A new paradigm in cell therapy for diabetes: turning pancreatic alpha-cells into
      beta-cells.
AB  - Cell therapy means treating diseases with the body's own cells. One of the cell
      types most in demand for therapeutic purposes is the pancreatic beta-cell. This
      is because diabetes is one of the major healthcare problems in the world.
      Diabetes can be treated by islet transplantation but the major limitation is the
      shortage of organ donors. To overcome the shortfall in donors, alternative
      sources of pancreatic beta-cells must be found. Potential sources include
      embryonic or adult stem cells or, from existing beta-cells. There is now a
      startling new addition to this list of therapies: the pancreatic alpha-cell.
      Thorel and colleagues recently showed that under circumstances of extreme
      pancreatic beta-cell loss, alpha-cells may serve to replenish the insulin
      producing compartment. This conversion of alpha-cells to beta-cells represents an
      example of transdifferentiation. Understanding the molecular basis for
      transdifferentiation may help to enhance the generation of beta-cells for the
      treatment of diabetes.

PMID- 20803506
TI  - Adam10 is essential for early embryonic cardiovascular development.
AB  - Notch pathway has been demonstrated to regulate cardiovascular development. One
      important step in Notch pathway is the cleavage of Notch receptor, during which
      an intracellular fragment of Notch protein is released to activate downstream
      genes. It is still uncertain whether Adam10, the mammalian homologue of Kuzbanian
      in Drosophila, is required to activate the Notch pathway during cardiovascular
      development. To further understand the physiological function of Adam10 in
      vascular and cardiac development, we generated mice lacking the Adam10 gene
      primarily in the endothelial compartment. We found that disruption of Adam10 in
      endothelial cells resulted in embryonic death after embryonic day 10.5 due to
      multiple cardiac and vascular defects similar to Notch1 mutants. We further
      showed that the expression of Notch target genes Snail and Bmp2 are impaired in
      Adam10-deficient cardiac tissues. Finally, we provide experimental evidence to
      support that Adam10 functions in a cell autonomous manner during mammalian
      cardiac development.

PMID- 20803507
TI  - Role of systems pharmacology in understanding drug adverse events.
AB  - Systems pharmacology involves the application of systems biology approaches,
      combining large-scale experimental studies with computational analyses, to the
      study of drugs, drug targets, and drug effects. Many of these initial studies
      have focused on identifying new drug targets, new uses of known drugs, and
      systems-level properties of existing drugs. This review focuses on systems
      pharmacology studies that aim to better understand drug side effects and adverse
      events. By studying the drugs in the context of cellular networks, these studies
      provide insights into adverse events caused by off-targets of drugs as well as
      adverse events-mediated complex network responses. This allows rapid
      identification of biomarkers for side effect susceptibility. In this way, systems
      pharmacology will lead to not only newer and more effective therapies, but safer
      medications with fewer side effects.

PMID- 20803508
TI  - Cyclooxygenase-2 (COX-2) polymorphisms and risk of inflammatory bowel disease in
      a Scottish and Danish case-control study.
AB  - BACKGROUND: Inflammatory bowel diseases (IBDs) are a result of interactions
      between luminal pathogens and the intestinal immune response. Cyclooxygenase-2
      (COX-2) plays a key role in the regulation of the inflammatory response upon
      stimulation by luminal pathogens via Toll-like receptors. METHODS: Genotypes of
      the COX-2/PTGS2/PGHS2 A-1195G (rs689466), G-765C (rs20417), and T8473C (rs5275)
      polymorphisms were assessed in a Scottish and Danish case-control study including
      732 Crohn's disease (CD) cases, 973 ulcerative colitis (UC) cases, and 1157
      healthy controls using logistic regression. RESULTS: Carriers of the COX-2 A
      1195G variant allele had increased risk of UC (odds ratio [OR], 95% confidence
      interval [CI] = 1.25 [1.02-1.54], P = 0.03) and of both UC and IBD among never
      smokers (OR [95% CI] = 1.47 [1.11-1.96], P = 0.01 and OR [95% CI] = 1.37 [1.06
      1.77], P = 0.02, respectively). Furthermore, this variant genotype was associated
      with increased risk of diagnosis of UC before age 40 years and with extensive UC
      (OR [95% CI] = 1.34 [1.11-1.62], P = 0.002 and OR [95% CI] = 1.32 [1.03-1.69], P
      = 0.03, respectively). CONCLUSIONS: COX-2 A-1195G polymorphism was associated
      with the risk of UC, especially among never-smokers, suggesting that low activity
      of COX-2 may predispose to UC. Our results suggest that inclusion of smoking
      status may be essential for the evaluation of the role of genetic predisposition
      to IBD.

PMID- 20803509
TI  - Advanced magnetic resonance imaging in benign hereditary chorea: study of two
      familial cases.
AB  - No brain abnormalities are usually detected on conventional magnetic resonance
      imaging (MRI) in benign hereditary chorea (BHC); there are currently no studies
      with advanced techniques in literature. We investigated whether conventional and
      advanced MRI techniques could depict regional brain abnormalities in two familial
      BHC patients and 24 healthy controls. No brain abnormalities on conventional
      scans were detectable; also, no significant differences in fractional anisotropy
      of the basal nuclei were observed. Volumetric analysis showed a decreased volume
      of the striatum bilaterally compared with controls, whereas spectroscopy
      demonstrated a significant increased myoinositol/creatine ratio bilaterally, a
      reduction of choline/creatine ratio bilaterally, and of N-acetyl
      aspartate/creatine in the right putamen. With the limits of the small sample size
      in the patient group, these data show that, despite the absence of macroscopic
      changes on conventional MRI, volumetric and metabolic abnormalities are present
      in the basal nuclei of BHC patients.

PMID- 20803510
TI  - Dysplastic lesions in ulcerative colitis: changing paradigms.
AB  - Crohn and Rosenberg first highlighted the increased risk of colorectal cancer in
      ulcerative colitis in 1925. Cancer rates as high as 34 percent after 30 yrs of
      disease have been reported in several population-based studies, although the
      reported risk varies substantially. Lower rates have been reported in: population
      versus specialist centre-cohorts, local practices with a high colectomy rate and
      high 5-aminosalicylate usage, and more recent as opposed to older reports.
      Despite this variation in reported risk, and lack of controlled evidence for
      cancer reduction, colonoscopic surveillance programmes are a routine part of care
      in many centres. Cancer is believed to arise most commonly in dysplastic
      epithelium, and the detection of either dysplasia or early cancer forms the basis
      of such programmes. Further confusion stems from the variety of terms used to
      describe dysplastic change.

PMID- 20803511
TI  - POLG, but not PEO1, is a frequent cause of cerebellar ataxia in Central Europe.
AB  - Nuclear genes, in particular mitochondrial polymerase gamma (POLG) and PEO1, have
      been increasingly recognized to cause mitochondrial diseases. Both genes assume a
      complementary role as part of the mitochondrial DNA (mtDNA) replication fork and,
      accordingly, seem to present with largely overlapping phenotypical spectra. We
      assessed the frequency and phenotypic spectrum of PEO1 compared to POLG mutations
      in a cohort of 80 patients with cerebellar ataxia for which common repeat
      expansion diseases had been excluded. Patients were selected to present
      additional features previously described for PEO1 mutations, namely early age of
      onset, progressive external ophthalmoplegia (PEO), or epilepsy. Whereas PEO1
      mutations were not found in our cohort, POLG frequently caused ataxia with PEO
      (47%), psychiatric comorbidities (20%) and, more rarely, with epilepsy (14%).
      Thus, PEO1 is rare in Central Europe even in those patients displaying
      characteristic phenotypic features. In contrast, POLG is rather common in Central
      European ataxia patients. It should be particularly considered in ataxia patients
      with PEO, psychiatric comorbidities, and/or sensory neuropathy, even if
      characteristic mitochondrial extra-CNS features are absent.

PMID- 20803512
TI  - What is the functional significance of nondominant arm tremor in essential
      tremor?
AB  - Tremor in the dominant arm is often the focus of clinical attention in essential
      tremor (ET) yet many daily activities require both arms. The functional relevance
      of nondominant arm tremor has rarely been studied. In 181 right-handed patients
      with ET, action tremor in each arm was rated using a clinical rating scale.
      Tremor disability was self-reported and a performance-based test of function was
      administered. Independently of tremor on the right, greater tremor severity on
      the left was associated with greater self-reported disability (P = 0.02) and
      greater performance-based dysfunction (P < 0.001). In 5.0% of patients, tremor
      was largely restricted to the nondominant arm. Nondominant arm tremor,
      independent of dominant arm tremor, had a significant functional correlate,
      contributing to both greater perceived and greater observable functional
      difficulty. In 5% of patients, tremor in the nondominant arm was the likely
      motivator for seeking care, which is another indication of its functional
      significance. (c) 2010 Movement Disorder Society.

PMID- 20803513
TI  - HIV, HAART, and Parkinson's disease: co-incidence or pathogenetic link?

PMID- 20803514
TI  - Iatrogenic belly dancer syndrome following quadruple deep brain stimulation in a
      patient with myoclonus dystonia (DYT11).

PMID- 20803516
TI  - Reply: An exploration of the burden experienced by spousal caregivers of
      individuals with Parkinson's disease.

PMID- 20803517
TI  - Familial nonkinesigenic paroxysmal dyskinesia and intracranial calcifications: a
      new syndrome?

PMID- 20803518
TI  - The road more traveled--common pitfalls on the way to a patent.
AB  - Drug delivery and diagnostic imaging patents represent an important subset of
      patents in the field of nananomedicine. In this article we review the most common
      rejections issued by the U.S. Patent and Trademark Office relating to these
      technologies. In particular, we found that the most common rejections are
      anticipation, obviousness and enablement. We also review the most common
      strategies used to overcome these rejections, which relate to "teaching away"
      arguments or claim amendment.

PMID- 20803519
TI  - Distinct basal ganglia hyperechogenicity in idiopathic basal ganglia
      calcification.
AB  - We report a 67-year-old patient with idiopathic basal ganglia calcification
      (IBGC). He presented with progressive cognitive impairment, frontal lobe
      dysfunction, mild leg spasticity, and levodopa (L-dopa)-responsive parkinsonism.
      Transcranial sonography (TCS) revealed marked hyperechogenicity of the basal
      ganglia and periventricular spaces bilaterally. The detected signal alterations
      showed a fairly symmetric distribution and corresponded to the hyperintense
      calcifications depicted on the computer tomography brain scan. The combination of
      symmetric hyperechogenic areas adjacent to the lateral ventricles and of the
      basal ganglia may serve as an imaging marker characteristic of IBGC.
      Hyperechogenicity due to extended basal ganglia calcification as presented here
      is distinct from the pattern of hyperechogenicity caused by heavy metal
      accumulation, which is described to be less striking. In addition to atypical
      parkinsonian syndromes such as progressive supranuclear palsy and multiple system
      atrophy, IBGC is thus another differential diagnosis of parkinsonism with basal
      ganglia hyperechogenicity.

PMID- 20803521
TI  - Opioid-modulating properties of the neuropeptide FF system.
AB  - Opioid receptors are involved in the control of pain perception in the central
      nervous system together with endogenous neuropeptides, termed opioid-modulating
      peptides, participating in a homeostatic system. Neuropeptide FF (NPFF) and
      related peptides possess anti-opioid properties, the cellular mechanisms of which
      are still unclear. The purpose of this review is to detail the phenomenon of
      cross-talk taking place between opioid and NPFF systems at the in vivo
      pharmacological level and to propose cellular and molecular models of
      functioning. A better knowledge of the mechanisms underlying opioid-modulating
      properties of NPFF has potential therapeutic interest for the control of opioid
      functions, notably for alleviating pain and/or for the treatment of opioid abuse.

PMID- 20803520
TI  - Retinoic acid: a key player in immunity.
AB  - For the past 100 years, vitamin A has been implicated as an essential dietary
      component in host resistance to infectious disease. However, only recently have
      studies begun to elucidate the cellular and molecular mechanisms of how vitamin A
      regulates cell-mediated and humoral-mediated immunity. In this review, we present
      an overview of the recent discoveries of the role that vitamin A and its
      metabolite, retinoic acid (RA), play in the regulation of immune cells. How RA
      impacts on leukocyte growth, differentiation, and homing is discussed with
      special attention to inflammatory responses and solid tumor microenvironment.

PMID- 20803522
TI  - Phytochemicals and adipogenesis.
AB  - Obesity is an increasing health problem all over the world. Phytochemicals are
      potential agents to inhibit differentiation of preadipocytes, stimulate
      lipolysis, and induce apoptosis of existing adipocytes, thereby reducing the
      amount of adipose tissue. Flavonoids and stilbenoids represent the most
      researched groups of phytochemicals with regards to their effect on adipogenesis,
      but there are also a number of in vitro and in vivo studies with phenolic acids,
      alkaloids, and vitamins, as well as other plant compounds. Although
      phytochemicals like epigallocatechin-3-gallate, genistein, and resveratrol reduce
      lipid accumulation and induce adipocyte apoptosis in vitro and reduce body weight
      and adipose tissues mass in animal models of diet-induced obesity, well-conducted
      clinical trials are lacking. Pharmacological doses are often used in vitro and
      when applied in physiological doses in animals or humans, the phytochemicals are
      often ineffective in affecting adipogenesis. However, by combining several
      phytochemicals or using them as templates for synthesizing new drugs, there is a
      large potential in targeting adipogenesis using phytochemicals.

PMID- 20803523
TI  - Phlorotannins from Ecklonia cava (Phaeophyceae): biological activities and
      potential health benefits.
AB  - The importance of bioactive derivatives as functional ingredients has been well
      recognized due to their valuable health beneficial effects. Therefore, isolation
      and characterization of novel functional ingredients with biological activities
      from seaweeds have gained much attention. Ecklonia cava Kjellman is an edible
      seaweed, which has been recognized as a rich source of bioactive derivatives
      mainly, phlorotannins. These phlorotannins exhibit various beneficial biological
      activities such as antioxidant, anticancer, antidiabetic, anti-human
      immunodeficiency virus, antihypertensive, matrix metalloproteinase enzyme
      inhibition, hyaluronidase enzyme inhibition, radioprotective, and antiallergic
      activities. This review focuses on biological activities of phlorotannins with
      potential health beneficial applications in functional foods, pharmaceuticals,
      and cosmeceuticals.

PMID- 20803525
TI  - SIRT1 modulates high-mobility group box 1-induced osteoclastogenic cytokines in
      human periodontal ligament cells.
AB  - Bone resorptive cytokines contribute to bone loss in periodontal disease.
      However, the involvement of SIRT1 in high-mobility group box 1 (HMGB1)-induced
      osteoclastic cytokine production remains unknown. The aim of this study was to
      investigate the role of SIRT1 in the responses of human periodontal ligament
      cells to HMGB1 and to identify the underlying mechanisms. The effect of HMGB1 on
      osteoclastic cytokine expression and secretion, and the regulatory mechanisms
      involved were studied by ELISA, reverse transcription-polymerase chain reaction,
      and Western blot analysis. HMGB1 upregulated the mRNA expression levels of the
      osteoclastic cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta,
      IL-6, IL-11, and IL-17. In addition, HMGB1 upregulated RANKL mRNA expression, and
      SIRT1 mRNA and protein expression. The upregulation of these cytokines by HMGB1
      was attenuated by pretreatment with inhibitors of p38 mitogen-activated protein
      kinase and NF-kappaB, as well as neutralizing antibodies against Toll-like
      receptors 2 and 4. Inhibition of SIRT1 by sirtinol or SIRT1 siRNA blocked the
      HMGB1-stimulated expression of RANKL and cytokines. These results suggest that
      the inhibition of SIRT1 may attenuate HMGB1-mediated periodontal bone resorption
      through the modulation of osteoclastogenic cytokine levels in human periodontal
      ligament cells.

PMID- 20803524
TI  - Effects of resveratrol and flavonols on cardiovascular function: Physiological
      mechanisms.
AB  - Resveratrol and flavonols are commonly found together in fruits and vegetables
      and, therefore, consumed in the diet. These two polyphenols share both
      vasorelaxant and antioxidant activity and may act together to improve
      cardiovascular function. This review examines the mechanisms by which resveratrol
      and flavonols influence cardiovascular function and perhaps offer a new approach
      for the development of therapeutic agents for the prevention and/or treatment of
      coronary artery disease.

PMID- 20803526
TI  - Nitric oxide involved in the IL-1beta-induced inhibition of fructose intestinal
      transport.
AB  - Interleukin-1beta (IL-1beta) is a pleiotropic cytokine produced by cells of the
      immune system and a large variety of other cell types including endothelial
      cells. It is released during inflammatory and infectious diseases, and possesses
      a wide spectrum of autocrine, paracrine and endocrine activities. The aim of this
      work was to examine the IL-1beta effect on D-fructose transport across rabbit
      jejunum and try to identify the mediators implicated in this process. A sepsis
      condition was induced for 90 min after intravenous (iv) administration of IL
      1beta and body temperature was recorded. Studies on cellular intestinal integrity
      have not shown modifications of the epithelium and the basement membrane. D
      fructose intestinal transport was studied in rabbit jejunum from control and
      treated animals and it was reduced in the latter ones. This cytokine decreased
      both the mucosal to serosal transepithelial flux and the transport across brush
      border membrane vesicles of D-fructose. The inhibition was reversed by L-NAME
      (nitric oxide [NO] synthase inhibitor), but not by indomethacin (cyclooxygenase 1
      and 2 inhibitor). Both inhibitors were administered iv 15 min before the IL
      1beta. The protein levels of GLUT5 were not changed in all animal groups and
      those of mRNA were even increased. In summary, these findings indicate that IL
      1beta, at the time assayed, induced a significant reduction in the relative
      intrinsic activity of GLUT5 and in this decrease are involved NO signalling
      pathways. In this way, blockage of D-fructose intestinal uptake by IL-1beta may
      be playing an essential role in the pathophysiology of septic shock.

PMID- 20803527
TI  - Role of the charge transfer state in organic donor-acceptor solar cells.
AB  - Charge transfer complexes are interfacial charge pairs residing at the donor
      acceptor heterointerface in organic solar cell. Experimental evidence shows that
      it is crucial for the photovoltaic performance, as both photocurrent and open
      circuit voltage directly depend on it. For charge photogeneration, charge
      transfer complexes represent the intermediate but essential step between exciton
      dissotiation and charge extraction. Recombination of free charges to the ground
      state is via the bound charge transfer state before being lost to the ground
      state. In terms of the open circuit voltage, its maximum achievable value is
      determined by the energy of the charge transfer state. An important question is
      whether or not maximum photocurrent and maximum open circuit voltage can be
      achieved simultaneously. The impact of increasing the CT energy-in order to raise
      the open circuit voltage, but lowering the kinetic excess energy of the CT
      complexes at the same time-on the charge photogeneration will accordingly be
      discussed. Clearly, the fundamental understanding of the processes involving the
      charge transfer state is essential for an optimisation of the performance of
      organic solar cells.

PMID- 20803528
TI  - Biomimetic nanopatterns as enabling tools for analysis and control of live cells.
AB  - It is becoming increasingly evident that cell biology research can be
      considerably advanced through the use of bioengineered tools enabled by nanoscale
      technologies. Recent advances in nanopatterning techniques pave the way for
      engineering biomaterial surfaces that control cellular interactions from the nano
      to the microscale, allowing more precise quantitative experimentation capturing
      multi-scale aspects of complex tissue physiology in vitro. The spatially and
      temporally controlled display of extracellular signaling cues on nanopatterned
      surfaces (e. g., cues in the form of chemical ligands, controlled stiffness,
      texture, etc.) that can now be achieved on biologically relevant length scales is
      particularly attractive enabling experimental platform for investigating
      fundamental mechanisms of adhesion-mediated cell signaling. Here, we present an
      overview of bio-nanopatterning methods, with the particular focus on the recent
      advances on the use of nanofabrication techniques as enabling tools for studying
      the effects of cell adhesion and signaling on cell function. We also highlight
      the impact of nanoscale engineering in controlling cell-material interfaces,
      which can have profound implications for future development of tissue engineering
      and regenerative medicine.

PMID- 20803529
TI  - Colloidal self-assembly meets nanofabrication: from two-dimensional colloidal
      crystals to nanostructure arrays.
AB  - Self-assembly of colloidal microspheres or nanospheres is an effective strategy
      for fabrication of ordered nanostructures. By combination of colloidal self
      assembly with nanofabrication techniques, two-dimensional (2D) colloidal crystals
      have been employed as masks or templates for evaporation, deposition, etching,
      and imprinting, etc. These methods are defined as "colloidal lithography", which
      is now recognized as a facile, inexpensive, and repeatable nanofabrication
      technique. This paper presents an overview of 2D colloidal crystals and
      nanostructure arrays fabricated by colloidal lithography. First, different
      methods for fabricating self-assembled 2D colloidal crystals and complex 2D
      colloidal crystal structures are summarized. After that, according to the
      nanofabrication strategy employed in colloidal lithography, related works are
      reviewed as colloidal-crystal-assisted evaporation, deposition, etching,
      imprinting, and dewetting, respectively.

PMID- 20803530
TI  - Coordination modulation induced synthesis of nanoscale Eu(1-x)Tb(x)-metal-organic
      frameworks for luminescent thin films.
AB  - Strategies for synthesizing of nanoscale single or bimetallic lanthanide metal
      organic framework (MOF) materials and their transformation into Eu(1-x)Tb(x)-MOF
      thin films are reported. The thin films prepared via spin coating deposition
      method are smooth, dense and mechanically stable. They also exhibit marked
      luminescent properties and efficient Tb(3+)-to-Eu(3+) energy transferability.

PMID- 20803531
TI  - Development of laser dyes to realize low threshold in dye-doped cholesteric
      liquid crystal lasers.

PMID- 20803532
TI  - Pyridoindole derivative as electron transporting host material for efficient deep
      blue phosphorescent organic light-emitting diodes.

PMID- 20803533
TI  - Correlation between tissue oxygenation and erythrocytes elasticity.
AB  - In this paper, near-infrared spectroscopy (NIRS) and jumping optical tweezers
      were used to measure the tissue oxygenation and the elasticity of erythrocytes,
      respectively. The correlation between tissue oxygenation induced by arterial
      occlusion test (AOT) and the mechanical properties of individual erythrocytes
      from a blood sample obtained after AOT was studied. The experimental results show
      a linear correlation between the oxygenation signal caused by AOT and the
      elasticity of erythrocytes.

PMID- 20803534
TI  - On ejecting colloids against capillarity from sub-micrometer openings: on-demand
      dielectrophoretic nanoprinting.

PMID- 20803535
TI  - Glutathione-induced intracellular release of guests from mesoporous silica
      nanocontainers with cyclodextrin gatekeepers.

PMID- 20803537
TI  - Dynamic and reversible organization of zeolite L crystals induced by holographic
      optical tweezers.
AB  - Organization and patterning of zeolite L crystals with their unique properties
      such as their one-dimensional nano channel system is of highest topical interest
      with various applications in many areas of science. We demonstrate full three
      dimensional optical control of single zeolite L crystals and for the first time
      fully reversible, dynamic organization of a multitude of individually controlled
      zeolite L crystals.

PMID- 20803536
TI  - Spray-deposited Li-doped ZnO transistors with electron mobility exceeding 50
      cm2/Vs.

PMID- 20803538
TI  - Water-based electrolytes for dye-sensitized solar cells.

PMID- 20803539
TI  - Hydrogen sensing using pd-functionalized multi-layer graphene nanoribbon
      networks.

PMID- 20803540
TI  - Coexistence of filamentary and homogeneous resistive switching in Fe-doped SrTiO3
      thin-film memristive devices.

PMID- 20803542
TI  - Formation of self-organized superlattice nanotube arrays - embedding
      heterojunctions into nanotube walls.

PMID- 20803541
TI  - Gel-immobilized colloidal crystal shell with enhanced thermal sensitivity at
      photonic wavelengths.

PMID- 20803543
TI  - Broadly absorbing black to transmissive switching electrochromic polymers.

PMID- 20803544
TI  - Recombination dynamics as a key determinant of open circuit voltage in organic
      bulk heterojunction solar cells: a comparison of four different donor polymers.

PMID- 20803545
TI  - FGF2 promotes Msx2 stimulated PC-1 expression via Frs2/MAPK signaling.
AB  - PC-1 is an enzymatic generator of pyrophosphate and a critical regulator of
      tissue mineralization. We previously showed that fibroblast growth factor-2
      (FGF2) specifically induces PC-1 expression in calvarial pre-osteoblasts and that
      this occurs via a transcriptional mechanism involving Runx2. Because aberrant FGF
      signaling and Msx2 activity result in similar craniofacial skeletal defects and
      because Msx2 is an established regulator of osteoblastic gene expression, here we
      investigate Msx2 as an additional mediator of PC-1 gene expression. mRNA analysis
      and experiments utilizing PC-1 gene promoter/luciferase reporter constructs
      demonstrate that Msx2 promotes transcription of the PC-1 gene downstream of FGF2.
      Results indicate that both Msx2 and Runx2 are recruited to a conserved core Msx2
      binding site within the PC-1 gene promoter upon FGF2 stimulation, and that Msx2
      and Runx2 function together to induce PC-1 gene expression in osteoblastic cells.
      Here we show that FGF signaling promotes Msx2 transcriptional activity on the PC
      1 gene promoter via the Frs2/MAPK signaling pathway. To our knowledge, this is
      the first report of Msx2 functioning as a transcriptional enhancer downstream of
      FGF2 in calvarial pre-osteoblasts. As activating mutations in FGF receptors and
      Msx2 result in similar craniofacial skeletal disorders, our findings support the
      idea that FGF signaling and Msx2 activity influence cranial osteogenesis via the
      same molecular mechanism.

PMID- 20803546
TI  - Compressive mechanical force augments osteoclastogenesis by bone marrow
      macrophages through activation of c-Fms-mediated signaling.
AB  - Little is known about the effects of mechanical forces on osteoclastogenesis by
      bone marrow macrophages (BMMs) in the absence of mechanosensitive cells,
      including osteoblasts and fibroblasts. In this study, we examined the effects of
      mechanical force on osteoclastogenesis by applying centrifugal force to BMMs
      using a horizontal microplate rotor. Our findings, as measured by an in vitro
      model system, show that tumor necrosis factor (TNF)-alpha is capable of inducing
      osteoclast differentiation from BMMs and bone resorption in the presence of
      macrophage-colony stimulating factor (M-CSF) and is further facilitated by
      receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL).
      Application of force to BMMs accelerated TNF-alpha-induced osteoclastogenesis;
      this was inhibited either by anti-TNF-alpha or anti-TNF-alpha receptor but not by
      OPG. TNF-alpha also increased c-Fms expression at both mRNA and protein levels in
      BMMs. An anti-c-Fms antibody completely inhibited osteoclast differentiation and
      bone resorption induced by TNF-alpha but partially blocked osteoclastogenesis
      stimulated in combination with RANKL. These results suggest that TNF-alpha (in
      the presence of M-CSF) is capable of inducing osteoclastogenesis from BMMs, and
      that osteoclastogenesis is significantly stimulated by force application through
      the activation of c-Fms-mediated signaling. Overall, the present study reveals
      the facilitating effect of mechanical force on osteoclastic differentiation from
      BMMs without the addition of mechanosensitive cells.

PMID- 20803547
TI  - Glypican 3 binds to GLUT1 and decreases glucose transport activity in
      hepatocellular carcinoma cells.
AB  - Glypican 3 (GPC3), a member of heparin sulfate proteoglycans, is attached to the
      cell surface by a glycosylphosphatidylinositol anchor and is reported to be
      overexpressed in liver cancers. In order to identify GPC3 binding proteins on the
      cell surface, we constructed a cDNA containing the C-terminal cell surface
      attached form of GPC3 (GPC3c) in a baculoviral vector. The GPC3c bait protein was
      produced by expressing the construct in Sf21 insect cells and double purified
      using a His column and Flag immunoprecipitation. Purified GPC3c was used to
      uncover GPC3c-interacting proteins. Using an LC-MS/MS proteomics strategy, we
      identified glucose transporter 1 (GLUT1) as a novel GPC3 interacting protein from
      the HepG2 hepatoma cell lysates. The interaction was confirmed by
      immunoprecipitation (IP)-WB analysis and surface plasmon resonance (SPR). SPR
      result showed the interaction of GLUT1 to GPC3c with equilibrium dissociation
      constants (K(D) ) of 1.61 nM. Moreover, both incubation with GPC3c protein and
      transfection of Gpc3c cDNA into HepG2 cells resulted in reduced glucose uptake
      activity. Our results indicate that GPC3 plays a role in glucose transport by
      interacting with GLUT1.

PMID- 20803549
TI  - Identification of a functional hepatocyte nuclear factor 4 binding site in the
      neutral ceramidase promoter.
AB  - The brush border membrane of the differentiated small intestinal epithelial cell
      is studded with membrane bound hydrolytic ectoenzymes involved in digestion.
      Previous studies of the regulation of genes encoding brush border enzymes have
      especially implicated the transcription factors hepatocyte nuclear factor HNF-1
      and Cdx2. Recent genome-wide studies have, however, also identified HNF-4alpha as
      a transcription factor with a high number of target genes in the differentiated
      small intestinal epithelial cell. The Asah2 gene encodes neutral ceramidase,
      which is a hydrolytic brush border enzyme involved in ceramide digestion. It was
      the purpose of the present work to experimentally verify the functional
      importance of a HNF-4alpha binding site predicted by bioinformatic analysis to be
      present in the Asah2 promoter. Using supershift analysis, HNF-4alpha
      overexpression, and HNF-4alpha knockdown experiments it was confirmed that the
      predicted HNF-4alpha binding site identified in the Asah2 promoter is functional.
      The results support the hypothesis that HNF-4alpha might be important for
      intestinal glycolipid metabolism.

PMID- 20803548
TI  - Optimizing stem cell culture.
AB  - Stem cells always balance between self-renewal and differentiation. Hence, stem
      cell culture parameters are critical and need to be continuously refined
      according to progress in our stem cell biology understanding and the latest
      technological developments. In the past few years, major efforts have been made
      to define more precisely the medium composition in which stem cells grow or
      differentiate. This led to the progressive replacement of ill-defined additives
      such as serum or feeder cell layers by recombinant cytokines or growth factors.
      Another example is the control of the oxygen pressure. For many years cell
      cultures have been done under atmospheric oxygen pressure which is much higher
      than the one experienced by stem cells in vivo. A consequence of cell metabolism
      is that cell culture conditions are constantly changing. Therefore, the
      development of high sensitive monitoring processes and control algorithms is
      required for ensuring cell culture medium homeostasis. Stem cells also sense the
      physical constraints of their microenvironment. Rigidity, stiffness, and geometry
      of the culture substrate influence stem cell fate. Hence, nanotopography is
      probably as important as medium formulation in the optimization of stem cell
      culture conditions. Recent advances include the development of synthetic
      bioinformative substrates designed at the micro- and nanoscale level. On going
      research in many different fields including stem cell biology, nanotechnology,
      and bioengineering suggest that our current way to culture cells in Petri dish or
      flasks will soon be outdated as flying across the Atlantic Ocean in the
      Lindbergh's plane.

PMID- 20803550
TI  - p53 and p21(Waf1) are recruited to distinct PML-containing nuclear foci in
      irradiated and Nutlin-3a-treated U2OS cells.
AB  - Promyelocytic leukemia nuclear bodies (PML-NBs) are multiprotein complexes that
      include PML protein and localize in nuclear foci. PML-NBs are implicated in
      multiple stress responses, including apoptosis, DNA repair, and p53-dependent
      growth inhibition. ALT-associated PML bodies (APBs) are specialized PML-NBs that
      include telomere-repeat binding-factor TRF1 and are exclusively in telomerase
      negative tumors where telomere length is maintained through alternative (ALT)
      recombination mechanisms. We compared cell-cycle and p53 responses in ALT
      positive cancer cells (U2OS) exposed to ionizing radiation (IR) or the p53
      stabilizer Nutlin-3a. Both IR and Nutlin-3a caused growth arrest and comparable
      induction of p53. However, p21, whose gene p53 activates, displayed biphasic
      induction following IR and monophasic induction following Nutlin-3a. p53 was
      recruited to PML-NBs 3-4 days after IR, approximately coincident with the
      secondary p21 increase. These p53/PML-NBs marked sites of apparently unrepaired
      DNA double-strand breaks (DSBs), identified by colocalization with phosphorylated
      histone H2AX. Both Nutlin-3a and IR caused a large increase in APBs that was
      dependent on p53 and p21 expression. Moreover, p21, and to a lesser extent p53,
      was recruited to APBs in a fraction of Nutlin-3a-treated cells. These data
      indicate (1) p53 is recruited to PML-NBs after IR that likely mark unrepaired
      DSBs, suggesting p53 may either be further activated at these sites and/or
      function in their repair; (2) p53-p21 pathway activation increases the percentage
      of APB-positive cells, (3) p21 and p53 are recruited to ALT-associated PML-NBs
      after Nutlin-3a treatment, suggesting that they may play a previously
      unrecognized role in telomere maintenance.

PMID- 20803551
TI  - Characterization of E2F3a function in HepG2 liver cancer cells.
AB  - E2F3a is a transcription factor that has been shown to be overexpressed in liver
      cancer tissues. To characterize the function of E2F3a in hepatocellular carcinoma
      (HCC), effects of ectopic overexpression of E2F3a on cell cycle, apoptosis, and
      gene expression of HepG2 cells were studied. E2F3a significantly enhances the
      apoptotic rate of HepG2 cells by 33% but only has minor effects on cell
      proliferation. By using microarray analyses, we identified 162 target genes (160
      upregulated and 2 downregulated) of the E2F3a. Differential expression of 11
      genes was further confirmed by real-time PCR. Eight of these 11 genes, including
      XAF1, CEACAM1, STAT1, ATF3, TNFSF10, KLF6, CLDN1, and TAP1, were confirmed to be
      upregulated by more than twofold. Functional enrichments of differentially
      expressed genes retrieved 21 apoptosis-related genes and 32 transcriptional
      regulation-related genes. These results suggest that E2F3a induces apoptosis in
      HepG2 cells and plays important roles in regulating transcription. Finally,
      positive correlation was found between E2F3a and CEACAM1 mRNA levels in
      clinically well-differentiated human HCC specimens.

PMID- 20803553
TI  - Angiogenesis and inflammation signaling are targets of beer polyphenols on
      vascular cells.
AB  - Emerging evidence indicates that chronic inflammation and oxidative stress
      cluster together with angiogenic imbalance in a wide range of pathologies. In
      general, natural polyphenols present health-protective properties, which are
      likely attributed to their effect on oxidative stress and inflammation. Hops used
      in beer production are a source of polyphenols such as xanthohumol (XN), and its
      metabolites isoxanthohumol (IXN) and phytoestrogen 8-prenylnaringenin (8PN). Our
      study aimed to evaluate XN, IXN, and 8PN effects on angiogenesis and inflammation
      processes. Opposite in vitro effects were observed between 8PN, stimulating
      endothelial and smooth muscle cell (SMC) growth, motility, invasion and capillary
      like structures formation, and XN and IXN, which inhibited them. Mouse matrigel
      plug and rat skin wound-healing assays confirmed that XN and IXN treatments
      reduced vessel number as well as serum macrophage enzymatic activity, whereas 8PN
      increased blood vessels formation in both assays and enzyme activity in the wound
      healing assay. A similar profile was found for serum inflammatory interleukin
      1beta quantification, in the wound-healing assay. Our data indicate that whereas
      8PN stimulates angiogenesis, XN and IXN manifested anti-angiogenic and anti
      inflammatory effects in identical conditions. These findings suggest that the
      effects observed for individual compounds on vascular wall cells must be
      carefully taken into account, as these polyphenols are metabolized after in vivo
      administration. The modulation of SMC proliferation and migration is also of
      special relevance, given the role of these cells in many pathological conditions.
      Furthermore, these results may provide clues for developing useful therapeutic
      agents against inflammation- and angiogenesis-associated pathologies.

PMID- 20803552
TI  - Modulation of GEF-H1 induced signaling by heparanase in brain metastatic melanoma
      cells.
AB  - Mechanisms of brain metastatic melanoma (BMM) remain largely unknown.
      Understanding the modulation of signaling pathways that alter BMM cell invasion
      and metastasis is critical to develop new therapies for BMM. Heparanase has been
      widely implicated in cancer and is the dominant mammalian endoglycosidase which
      degrades heparan sulfate chains of proteoglycans (HSPG) including syndecans
      (SDCs). Recent findings also indicate that heparanase possesses non-enzymatic
      functions in its latent form. We hypothesized that extracellular heparanase
      modulates BMM cell signaling by involving SDC1/4 carboxy terminal-associated
      proteins and downstream targets. We digested BMM cell surface HS with human
      recombinant active or latent heparanase to delineate their effects on
      cytoskeletal dynamics and cell invasiveness. We identified the small GTPase
      guanine nucleotide exchange factor-H1 (GEF-H1) as a new component of a SDC
      signaling complex that is differentially expressed in BMM cells compared to
      corresponding non-metastatic counterparts. Second, knockdown of GEF-H1, SDC1, or
      SDC4 decreased BMM cell invasiveness and GEF-H1 modulated small GTPase activity
      of Rac1 and RhoA in conjunction with heparanase treatment. Third, both active and
      latent forms of heparanase affected Rac1 and RhoA activity; notably increasing
      RhoA activity. Both forms of heparanase were found to mediate the expression and
      subcellular localization of GEF-H1, and treatment of BMM with latent heparanase
      modulated SDC1/4 gene expression. Finally, treatment with exogenous heparanase
      downregulated BMM cell invasion. These studies indicate the relevance of
      heparanase signaling pathways in BMM progression, and provide insights into the
      molecular mechanisms regulating HSPG signaling in response to exogenous
      heparanase.

PMID- 20803554
TI  - Regulation of Borealin by phosphorylation at serine 219.
AB  - The chromosomal passenger complex consisting of Borealin, INCENP, Survivin, and
      Aurora B follows a dynamic pattern of localization to perform its role as a
      regulator of chromosome alignment, aspects of the spindle assembly checkpoint,
      and cytokinesis. Post-translational modifications of chromosomal passenger
      proteins play an important role in regulating the localization and function of
      the complex. Borealin displays a slower electrophoretic mobility during mitosis
      as a result of phosphorylation. Here we show that phosphorylation at S219 is
      responsible for this mobility shift. An S219A mutant of Borealin that cannot be
      phosphorylated at this site displays a defect in centromere localization that is
      evident in cells arrested in mitosis with nocodazole. Further, the S219A form of
      Borealin is unable to efficiently rescue mitotic defects that occur upon knock
      down of the endogenous protein. These defects are correlated with a reduction in
      the intensity of Mad2 staining at kinetochores in cells expressing the S219A form
      of Borealin. These results highlight an important role for phosphorylation of
      Borealin at S219 in the proper progression through mitosis.

PMID- 20803556
TI  - A nonlinear model for highly unbalanced repeated time-to-event data: Application
      to labor progression.
AB  - The collection of repeated measurements over time on an experimental unit to
      study the changes over time of a certain characteristic is common in biological
      and clinical studies. Data of this type are also often referred to as growth
      curve data or repeated measures data. There arise situations when one is
      interested in an estimate of the time to an event, based on a characteristic that
      indicates progression towards the event. The assessment of the progression of
      labor during childbirth based on cervical dilation is one such example. Here
      increase in the dilation of the cervix indicates progression towards delivery.
      Based on how long one has been in labor and an estimate of the time to complete
      dilation one might make crucial decisions like the decision to administer a drug
      or to perform a C-section. Here a repeated measures approach is developed to
      model the time to the event. The parameters of the model are estimated by a
      maximum likelihood approach. A general model is developed for a class of data
      structures and a nonlinear model is developed specific to the labor progression
      data. Simulations are performed to assess the methodology and conditions are
      suggested for predicting the time to an event.

PMID- 20803555
TI  - CB2 cannabinoid receptor targets mitogenic Gi protein-cyclin D1 axis in
      osteoblasts.
AB  - CB2 is a Gi protein-coupled receptor activated by endo- and phytocannabinoids,
      thus inhibiting stimulated adenylyl cyclase activity. CB2 is expressed in bone
      cells and Cb2 null mice show a marked age-related bone loss. CB2-specific
      agonists both attenuate and rescue ovariectomy-induced bone loss. Activation of
      CB2 stimulates osteoblast proliferation and bone marrow derived colony-forming
      units osteoblastic. Here we show that selective and nonselective CB2 agonists are
      mitogenic in MC3T3 E1 and newborn mouse calvarial osteoblastic cultures. The CB2
      mitogenic signaling depends critically on the stimulation of Erk1/2
      phosphorylation and de novo synthesis of MAP kinase-activated protein kinase 2
      (Mapkapk2) mRNA and protein. Further downstream, CB2 activation enhances CREB
      transcriptional activity and cyclin D1 mRNA expression. The CB2-induced
      stimulation of CREB and cyclin D1 is inhibitable by pertussis toxin, the MEK
      Erk1/2 inhibitors PD098059 and U0126, and Mapkapk2 siRNA. These data demonstrate
      that in osteoblasts CB2 targets a Gi protein-cyclin D1 mitogenic axis. Erk1/2
      phosphorylation and Mapkapk2 protein synthesis are critical intermediates in this
      axis.

PMID- 20803557
TI  - A sequential Cox approach for estimating the causal effect of treatment in the
      presence of time-dependent confounding applied to data from the Swiss HIV Cohort
      Study.
AB  - When estimating the effect of treatment on HIV using data from observational
      studies, standard methods may produce biased estimates due to the presence of
      time-dependent confounders. Such confounding can be present when a covariate,
      affected by past exposure, is both a predictor of the future exposure and the
      outcome. One example is the CD4 cell count, being a marker for disease
      progression for HIV patients, but also a marker for treatment initiation and
      influenced by treatment. Fitting a marginal structural model (MSM) using inverse
      probability weights is one way to give appropriate adjustment for this type of
      confounding. In this paper we study a simple and intuitive approach to estimate
      similar treatment effects, using observational data to mimic several randomized
      controlled trials. Each 'trial' is constructed based on individuals starting
      treatment in a certain time interval. An overall effect estimate for all such
      trials is found using composite likelihood inference. The method offers an
      alternative to the use of inverse probability of treatment weights, which is
      unstable in certain situations. The estimated parameter is not identical to the
      one of an MSM, it is conditioned on covariate values at the start of each
      mimicked trial. This allows the study of questions that are not that easily
      addressed fitting an MSM. The analysis can be performed as a stratified weighted
      Cox analysis on the joint data set of all the constructed trials, where each
      trial is one stratum. The model is applied to data from the Swiss HIV cohort
      study.

PMID- 20803558
TI  - Bayesian sample size for diagnostic test studies in the absence of a gold
      standard: Comparing identifiable with non-identifiable models.
AB  - Diagnostic tests rarely provide perfect results. The misclassification induced by
      imperfect sensitivities and specificities of diagnostic tests must be accounted
      for when planning prevalence studies or investigations into properties of new
      tests. The previous work has shown that applying a single imperfect test to
      estimate prevalence can often result in very large sample size requirements, and
      that sometimes even an infinite sample size is insufficient for precise
      estimation because the problem is non-identifiable. Adding a second test can
      sometimes reduce the sample size substantially, but infinite sample sizes can
      still occur as the problem remains non-identifiable. We investigate the further
      improvement possible when three diagnostic tests are to be applied. We first
      develop methods required for studies when three conditionally independent tests
      are available, using different Bayesian criteria. We then apply these criteria to
      prototypic scenarios, showing that large sample size reductions can occur
      compared to when only one or two tests are used. As the problem is now
      identifiable, infinite sample sizes cannot occur except in pathological
      situations. Finally, we relax the conditional independence assumption,
      demonstrating in this once again non-identifiable situation that sample sizes may
      substantially grow and possibly be infinite. We apply our methods to the planning
      of two infectious disease studies, the first designed to estimate the prevalence
      of Strongyloides infection, and the second relating to estimating the sensitivity
      of a new test for tuberculosis transmission. The much smaller sample sizes that
      are typically required when three as compared to one or two tests are used should
      encourage researchers to plan their studies using more than two diagnostic tests
      whenever possible. User-friendly software is available for both design and
      analysis stages greatly facilitating the use of these methods.

PMID- 20803559
TI  - Type 1 T helper cells induce the accumulation of myeloid-derived suppressor cells
      in the inflamed Tgfb1 knockout mouse liver.
AB  - Immune-mediated liver injury in hepatitis is due to activated T cells producing
      interferon-gamma (IFN-gamma). It is important to identify negative feedback
      immune mechanisms that can regulate T cell activity. In this study, we
      demonstrate that liver inflammation mediated by type 1 T helper (Th1) cells can
      induce the accumulation of myeloid-derived suppressor cells (MDSCs), pleiomorphic
      cells capable of modulating T cell-mediated immunity, that heretofore have been
      studied almost exclusively in the context of tumor-associated inflammation. Mice
      deficient in the gene encoding transforming growth factor-beta1 (Tgfb1(-/-) mice)
      acutely develop liver necroinflammation caused by IFN-gamma-producing clusters of
      differentiation 4-positive (CD4(+)) T cells. Liver Th1 cell accumulation was
      accompanied by myeloid cells expressing CD11b and Gr1, phenotypic hallmarks of
      MDSCs. Isolated Tgfb1(-/-) liver CD11b(+)Gr1(+) cells were functional MDSCs,
      readily suppressing T cell proliferation in vitro. Pharmacologic inhibitors of
      inducible nitric oxide (NO) synthase completely eliminated suppressor function.
      Suppressor function and the production of NO were dependent on cell-cell contact
      between MDSCs and T cells, and upon IFN-gamma, and were specifically associated
      with the "monocytic" CD11b(+)Ly6G(-) Ly6C(hi) subset of liver Tgfb1(-/-) CD11b(+)
      cells. The rapid accumulation of CD11b(+)Gr1(+) cells in Tgfb1(-/-) liver was
      abrogated when mice were either depleted of CD4(+) T cells or rendered unable to
      produce IFN-gamma, showing that Th1 activity induces MDSC accumulation.
      CONCLUSION: Th1 liver inflammation mobilizes an MDSC response that, through the
      production of NO, can inhibit T cell proliferation. We propose that MDSCs serve
      an important negative feedback function in liver immune homeostasis, and that
      insufficient or inappropriate activity of this cell population may contribute to
      inflammatory liver pathology.

PMID- 20803560
TI  - Endotoxin accumulation prevents carcinogen-induced apoptosis and promotes liver
      tumorigenesis in rodents.
AB  - Increasing evidence suggests that the presence of endotoxemia is of substantial
      clinical relevance to patients with cirrhosis, but it is unclear whether and how
      gut-derived LPS amplifies the tumorigenic response of the liver. We found that
      the circulating levels of LPS were elevated in animal models of carcinogen
      induced hepatocarcinogenesis. Reduction of LPS using antibiotics regimen in rats
      or genetic ablation of its receptor Toll-like receptor 4 (TLR4) in mice prevented
      excessive tumor growth and multiplicity. Additional investigation revealed that
      TLR4 ablation sensitizes the liver to carcinogen-induced toxicity via blocking NF
      kappaB activation and sensitizing the liver to reactive oxygen species (ROS)
      induced toxicity, but lessens inflammation-mediated compensatory proliferation.
      Reconstitution of TLR4-expressing myeloid cells in TLR4-deficient mice restored
      diethylnitrosamine (DEN)-induced hepatic inflammation and proliferation,
      indicating a paracrine mechanism of LPS in tumor promotion. Meanwhile, deletion
      of gut-derived endotoxin suppressed DEN-induced cytokine production and
      compensatory proliferation, whereas in vivo LPS pre-challenge promotes hepatocyte
      proliferation. CONCLUSION: Our data indicate that sustained LPS accumulation
      represents a pathological mediator of inflammation-associated hepatocellular
      carcinoma (HCC) and manipulation of the gut flora to prevent pathogenic bacterial
      translocation and endotoxin absorption may favorably influence liver function in
      patients with cirrhosis who are at risk of developing HCC.

PMID- 20803562
TI  - CHO cell expression, long-term stability, and primate pharmacokinetics and brain
      uptake of an IgG-paroxonase-1 fusion protein.
AB  - Paraoxonase (PON)-1 is the most potent human organophosphatase known, but
      recombinant forms of human PON1 have been difficult to produce owing to poor
      secretion by host cells. In the present investigation, human PON1 is re
      engineered as an IgG-PON1 fusion protein. The 355 amino acid human PON1 is fused
      to the carboxyl terminus of the heavy chain of a chimeric monoclonal antibody
      (MAb) against the human insulin receptor (HIR), and this fusion protein is
      designated HIRMAb-PON1. The HIRMAb part of the fusion protein enables brain
      penetration of the PON1, which was considered important, because organophosphate
      toxicity causes death via a central nervous system site of action. A high
      producing line of stably transfected Chinese hamster ovary (CHO) cells secreting
      the HIRMAb-PON1 fusion protein in the absence of serum or lipid acceptors was
      cloned. The bioreactor generated fusion protein was purified to homogeneity with
      low impurities by protein A affinity chromatography and anion exchange
      chromatography. The HIRMAb-PON1 fusion protein was stable as a sterile liquid
      formulation stored at 4 degrees C for at least 1 year. The plasma
      pharmacokinetics (PK) of the HIRMAb-PON1 fusion protein was evaluated in Rhesus
      monkeys, which is the first PK evaluation of a recombinant PON1 protein. The
      fusion protein was rapidly removed from blood, primarily by the liver. The blood
      brain barrier permeation of the HIRMAb-PON1 fusion protein was high and
      comparable to other HIRMAb fusion proteins. Re-engineering human PON1 as the
      HIRMAb fusion protein allows for production of a stable, field-deployable
      formulation of the enzyme that is brain-penetrating.

PMID- 20803563
TI  - Coupling glucose fermentation and homoacetogenesis for elevated acetate
      production: Experimental and mathematical approaches.
AB  - Homoacetogenesis is an important potential hydrogen sink in acetogenesis, in
      which hydrogen is used to reduce carbon dioxide to acetate. So far the acetate
      production from homoacetogenesis, especially its kinetics, has not been given
      sufficient attention. In this work, enhanced production of acetate from anaerobic
      conversion of glucose through coupling glucose fermentation and homoacetogenesis
      is investigated with both experimental and mathematical approaches. Experiments
      are conducted to explore elevated acetate production in a coupled anaerobic
      system. Acetate production could be achieved by homoacetogenesis with a relative
      high acetate yield under mixed fermentation conditions. With the experimental
      observations, a kinetic model is formulated to describe such a homoacetogenic
      process. The maximum homoacetogenic rate (k(m,homo)) is estimated to be 28.5 +/-
      1.7 kg COD kg-1 COD day-1 with an uptake affinity constant of 3.7 * 10-5+/- 3.1 *
      10-6kg COD m-3. The improved calculation of homoacetogenic kinetics by our
      approach could correct the underestimation of homoacetogenesis in anaerobic
      fermentation processes, as it often occurs in these systems supported by
      literature analysis. The model predictions match the experimental results in
      different cases well and provide insights into the dynamics of anaerobic glucose
      conversion and acetate production. Furthermore, acetate production via
      homoacetogenesis increases by about 40% through utilizing the fed-batch coupling
      system, attributed to a balance between the hydrogen production in the
      acetogenesis phase and the hydrogen consumption in the homoacetogenesis phase.
      This work provides an effective way for increased anaerobic acetate production,
      and gives us a better understanding about the homoacetogenic kinetics in the
      anaerobic fermentation process.

PMID- 20803561
TI  - Potential role for interleukin-28B genotype in treatment decision-making in
      recent hepatitis C virus infection.
AB  - Polymorphisms in the IL28B (interleukin-28B) gene region are important in
      predicting outcome following therapy for chronic hepatitis C virus (HCV)
      infection. We evaluated the role of IL28B in spontaneous and treatment-induced
      clearance following recent HCV infection. The Australian Trial in Acute Hepatitis
      C (ATAHC) was a study of the natural history and treatment of recent HCV, as
      defined by positive anti-HCV antibody, preceded by either acute clinical HCV
      infection within the prior 12 months or seroconversion within the prior 24
      months. Factors associated with spontaneous and treatment-induced HCV clearance,
      including variations in IL28B, were assessed. Among 163 participants, 132 were
      untreated (n = 52) or had persistent infection (infection duration >=26 weeks) at
      treatment initiation (n = 80). Spontaneous clearance was observed in 23% (30 of
      132 participants). In Cox proportional hazards analysis (without IL28B), HCV
      seroconversion illness with jaundice was the only factor predicting spontaneous
      clearance (adjusted hazards ratio = 2.86; 95% confidence interval = 1.24, 6.59; P
      = 0.014). Among participants with IL28B genotyping (n = 102 of 163 overall and 79
      of 132 for the spontaneous clearance population), rs8099917 TT homozygosity
      (versus GT/GG) was the only factor independently predicting time to spontaneous
      clearance (adjusted hazard ratio = 3.78; 95% confidence interval = 1.04, 13.76; P
      = 0.044). Participants with seroconversion illness with jaundice were more
      frequently rs8099917 TT homozygotes than other (GG/GT) genotypes (32% versus 5%,
      P = 0.047). Among participants adherent to treatment and who had IL28B genotyping
      (n = 54), sustained virologic response was similar among TT homozygotes (18 of 29
      participants, 62%) and those with GG/GT genotype (16 of 25, 64%, P = 0.884).
      CONCLUSION: During recent HCV infection, genetic variations in IL28B region were
      associated with spontaneous but not treatment-induced clearance. Early
      therapeutic intervention could be recommended for individuals with unfavorable
      IL28B genotypes.

PMID- 20803564
TI  - Aggregation of bovine anterior cruciate ligament fibroblasts or marrow stromal
      cells promotes aggrecan production.
AB  - The development of a tissue-engineered alternative for current ligament grafts
      requires the creation of a fibrocartilaginous interface between the engineered
      ligament midsubstance and bone tissue. Therefore, the focus of this study was to
      examine the potential for cartilaginous extracellular matrix (ECM) formation by
      altering culture parameters for bovine anterior cruciate ligament (ACL)
      fibroblasts and marrow stromal cells (MSCs). Specifically, cells were cultured
      without chondrogenic media supplements on aggrecan-coated surfaces, tissue
      culture-treated control surfaces, and nonadhesive surfaces that promoted cell
      aggregation, and examined over 14 days. Aggrecan-coated surfaces promoted the
      aggregation of ACL fibroblasts and MSCs within 24 h after seeding. Aggrecan gene
      expression was significantly upregulated in cell aggregates, regardless of how
      cell clustering was induced, with as much as 10.9 +/- 1.2-fold upregulation in
      ACL fibroblasts and 9.7 +/- 1.1-fold in MSCs after 3 days, compared to control
      surfaces. Dimethylmethylene blue (DMMB) results and immunostaining verified the
      presence of aggrecan in ACL fibroblast and MSC aggregates throughout the culture
      period. Results indicate that ACL fibroblasts retained the ability to alter their
      gene expression and produce aggrecan, though MSCs, in general, had a more
      consistent response to aggregation. These findings support the use of aggregate
      inducing materials to encourage production of aggrecan and suggest that altering
      the degree of clustering could produce a range of phenotypes from a single cell
      source. As such, this represents a first step which may inform future approaches
      to producing tissue-engineered ligament grafts.

PMID- 20803565
TI  - Comparative lipidomic profiling of xylose-metabolizing S. cerevisiae and its
      parental strain in different media reveals correlations between membrane lipids
      and fermentation capacity.
AB  - Phospholipids (PLs) serve as the foundation for structure and function in most
      cell membranes. In order to reveal the correlations between PLs composition and
      fermentation performance of cells, a comparative lipidomics study was carried out
      using a recombinant xylose fermenting yeast strain Saccharomyces cerevisiae
      424A(LNH-ST) and its parental strain 4124. Profiling of yeast lipids was
      performed using ultra performance liquid chromatography (UPLC)-MS/MS, leading to
      identification of 123 PL species. PL compositions were determined for both
      strains grown in rich medium (yeast extract peptone), limited medium (yeast
      nitrogen base), and ammonia fiber expansion pretreated corn stover hydrolysate.
      Principal component analysis of lipidomic data revealed that the PL profile for
      both strains varied significantly depending upon cultivating media composition.
      Further analysis of different classes of PLs revealed that the
      phosphatidylinositol/phosphatidylserine (PI/PS) ratio was closely related to cell
      growth rates. Both strains possessed higher phosphatidylcholine (PC) levels at an
      expense of phosphatidylethanolamine (PE) levels when entering stationary phase
      and the PC/PE ratios showed consistency with glucose utilization rates.
      Interestingly, PI synthesis lagged behind when available nutrients were limited,
      and PI levels were closely correlated with xylose metabolism.

PMID- 20803566
TI  - Pro-inflammatory angiogenesis is mediated by p38 MAP kinase.
AB  - Chronic inflammation is tightly linked to diseases associated with endothelial
      dysfunction including aberrant angiogenesis. To better understand the endothelial
      role in pro-inflammatory angiogenesis, we analyzed signaling pathways in
      continuously activated endothelial cells, which were either chronically exposed
      to soluble TNF or the reactive oxygen species (ROS) generating H2O2, or express
      active transmembrane TNF. Testing in an in vitro capillary sprout formation
      assay, continuous endothelial activation increased angiogenesis dependent on
      activation of p38 MAP kinase, NADPH oxidase, and matrix metalloproteinases (MMP).
      p38 MAP kinase- and MMP-9-dependent angiogenesis in our assay system may be part
      of a positive feed forward autocrine loop because continuously activated
      endothelial cells displayed up-regulated ROS production and subsequent
      endothelial TNF expression. The pro-angiogenic role of the p38 MAP kinase in
      continuously activated endothelial cells was in stark contrast to the anti
      angiogenic activity of the p38 MAP kinase in unstimulated control endothelial
      cells. In vivo, using an experimental prostate tumor, pharmacological inhibition
      of p38 MAP kinase demonstrated a significant reduction in tumor growth and in
      vessel density, suggesting a pro-angiogenic role of the p38 MAP kinase in
      pathological angiogenesis in vivo. In conclusion, our results suggest that
      continuous activation of endothelial cells can cause a switch of the p38 MAP
      kinase from anti-angiogenic to pro-angiogenic activities in conditions which link
      oxidative stress and autocrine TNF production.

PMID- 20803567
TI  - The styloid process and its relationship to the facial and hypoglossal nerves.

PMID- 20803568
TI  - An anatomical ultrasound study of the long posterior sacro-iliac ligament.
AB  - The long posterior sacro-iliac ligament (LPSL) is directly posterior to the sacro
      iliac joint and a potential source of lower back and pelvic pain. Its sonographic
      anatomy has not been described in detail. The aim of this study was to define and
      measure the ligament in healthy young women using ultrasound (US). The LPSL was
      scanned in 30 healthy women (median age, 22 years; range, 20-34) using a high
      resolution linear transducer (7.5-10 MHz). The ligament was consistently
      visualized as a hyperechoic laminated linear structure between the posterior
      superior iliac spine and the lateral aspect of the third transverse sacral
      tubercle. Its length, thickness, and the angle between it and the posterior
      superior iliac spine were measured by an experienced sonographer bilaterally in
      both semiflexed standing and lateral decubitus positions. Four female cadaver
      pelves (age range, 57-93 years) were also scanned and dissected to validate US
      observations. In the semiflexed standing position, mean LPSL length was 37.9 +/-
      2.4 mm, mean thickness 1.57 +/- 0.38mm, and median angle 18.5 degrees . There was
      no statistically significant difference with equivalent values in the lateral
      decubitus position. Intrarater repeatability was fair to substantial in both
      positions (intraclass correlation coefficient, 0.39-0.66), improving to moderate
      to substantial (intraclass correlation coefficient, 0.57-0.80) using the mean of
      two measurements. There was good overall agreement between LPSL length and
      thickness in cadavers measured by US and dissection. These findings document the
      sonographic appearance, length, and thickness of the LPSL and provide useful
      normative data for understanding potential LPSL pathology, particularly in
      relation to pregnancy-related pelvic girdle pain.

PMID- 20803569
TI  - Longitudinal study of breastfeeding structure and women's work in the Brazilian
      Amazon.
AB  - It is well established that breast milk is the ideal food for infants and that
      breastfeeding has short- and long-term health benefits for the mother and child.
      However, there is variation in breastfeeding patterns between populations.
      Women's work is thought to influence breastfeeding patterns and timing of
      supplementation and it is often assumed that women in subsistence-oriented
      societies can more easily integrate their productive and reproductive activities.
      This article reports longitudinal data, collected in three rounds (resguardo [<40
      days], peak [2-4 months], and late [14-16 months] lactation), on breastfeeding
      structure, infant care, and work patterns of 17 rural Amazonian women in an
      effort to understand how breastfeeding structure and maternal time allocation
      changed over time, as well as the strategies women used to integrate their
      productive and reproductive roles. Women breastfed 10.6 +/- 3.1, 9.4 +/- 3.4, and
      9.6 +/- 5.5 times per 9-h period in the three rounds, respectively. Breastfeeding
      structure, specifically session duration, changed over time (P < 0.05). As
      lactation progressed, women spent less time breastfeeding and in infant care and
      more time in subsistence work. In peak lactation, subsistence work was negatively
      correlated with infant care (r = -0.4, P = 0.01), breastfeeding (r = -0.29, P =
      0.05) and session duration (r = -0.39, P < 0.01) and in late lactation was
      negatively correlated with time spent breastfeeding (r = -0.39, P < 0.01) and in
      infant care (r = -0.50, P < 0.01) and positively correlated with inter-session
      interval (r = 0.40, P < 0.01). Generally, women reduced time in subsistence work
      when breastfeeding was more intense and returned to normal activity patterns once
      infants were being supplemented. The costs and benefits associated with women's
      strategies are discussed.

PMID- 20803571
TI  - Anatomic study of the suboccipital artery of Salmon with surgical significance.
AB  - The anatomy of the muscular branches of the vertebral arteries has clinical
      relevance during surgical procedures, suboccipital injections, and manual
      therapies. Each vertebral artery is divided into four segments. Segment V3, found
      in the suboccipital triangle, courses posteromedially around the lateral mass to
      lie in a groove on the posterior arch of the atlas, ultimately coursing beneath
      the posterior atlanto-occipital membrane to enter the skull. Although not always
      present, any muscular branch that emanates from this segment to supply the
      suboccipital muscles is called the suboccipital artery of Salmon. There is a
      paucity of literature on this artery despite its clinical relevancy. We found the
      suboccipital artery of Salmon in 10 (67%) of 15 embalmed adult cadavers. This
      frequency is considerably higher than that in previous reports. Two (20%) of the
      10 cadavers demonstrated bilateral and symmetrical suboccipital arteries of
      Salmon (one artery on each side). Four (40%) of the 10 cadavers had an
      arrangement of two parallel suboccipital arteries of Salmon on one side, and one
      on the contralateral side. Three (30%) of the 10 cadavers displayed an
      asymmetrical unilateral arrangement (only one artery). One (10%) of the 10
      cadavers displayed the unique arrangement of three arteries of Salmon on one side
      and one artery on the contralateral side. This study adds to a limited, but
      growing, body of knowledge by providing photographic evidence of the course and
      arrangement of these arteries and, therefore, can be of value to surgeons and
      other clinicians whose procedures focus on the suboccipital region.

PMID- 20803570
TI  - Giovanni Filippo Ingrassia: A five-hundred year-long lesson.
AB  - Giovanni Filippo Ingrassia was born five centuries ago in Regalbuto, a small town
      in the center of Sicily. After his medical course in Padua, under the guidance of
      Vesalius and Fallopius, he gained international fame as a physician and was
      recruited as a Professor of human anatomy in Naples and later in Palermo. He is
      remembered as "the new Galen" or "the Sicilian Hippocrates." He contributed to
      the knowledge of human anatomy through the description of single bones rather
      than the whole skeleton. In particular, he was the first to describe the
      "stapes," the "lesser wings of the sphenoid" and various other structures in the
      head (probably the pharyngotympanic tube) as well as in the reproductive system
      (corpora cavernosa and seminal vesicles). He was also a pioneer in the study of
      forensic medicine, hygiene, surgical pathology, and teratology. As Protomedicus
      of Sicily, he developed the scientific culture in this country. During those
      years, he faced the spread of malaria and plague with competence and
      authoritativeness. Indeed, he was one of the first physicians to suppose that
      certain diseases could be transmitted between individuals, therefore, introducing
      revolutionary measures of prevention. He is remembered for his intellectual
      authority and honesty. Five-hundred years after his birth, his teaching is still
      alive. In this article, we survey the life and contribution of this pioneer of
      early anatomical study.

PMID- 20803572
TI  - Three-dimensional morphometry of the A2 segment of the anterior cerebral artery
      with neurosurgical relevance.
AB  - Most prior morphometry data regarding the A2 segment of the anterior cerebral
      artery (ACA) have been based on cadaveric measurements. With newer imaging
      modalities, surgical techniques, and minimally invasive procedures, new standards
      for the anatomy of this vessel are necessary. A novel computer-based data system
      was used to analyze the three-dimensional (3D) morphometry of 230 A2 segments. In
      addition, tortuosity (TI) and deviation indices (DI) for this segment were
      calculated. The mean internal diameter of the A2 segment was 1.86 mm, and
      segments tended to be larger in men and on left sides. A2 segments were
      asymmetrical in 43%, and this was more common in women. Lengths tended to be
      greater on right sides and in men. Volumes were greater in men and increased with
      age, which was statistically significant. These gender differences were found to
      be statistically significant (P < 0.05), for both volume and diameter. TI was
      equal among sides, but DI was more often greater on right sides. The correlation
      coefficient ratio for length and DI was statistically significant. It is
      important to understand various 3D morphometrical differences particularly
      between genders. By constructing blood flow simulation models and during
      revascularization procedures, surgeons are able to gain a better understanding of
      each patient's vascular anatomy. These additional 3D data regarding the anatomy
      of the postcommunicating parts of the ACA may be useful to the neurosurgeon and
      interventional neuroradiologist. These data may assist with an earlier diagnosis
      of pathologies affecting the 3D morphology of the ACA.

PMID- 20803573
TI  - Degradation of polysorbates 20 and 80: studies on thermal autoxidation and
      hydrolysis.
AB  - The purpose of this work was to study the mechanistic pathways of degradation of
      polysorbates (PS) 20 and PS80 in parenteral formulations. The fate of PS in
      typical protein formulations was monitored and analyzed by a variety of methods,
      including (1)H NMR, high-performance liquid chromatography/evaporative light
      scattering detection, and ultraviolet-visible spectroscopy. Oxidative degradation
      of PS in neat raw material was studied using thermogravimetric analysis (TGA),
      differential scanning calorimetry (DSC), and headspace gas chromatography-mass
      spectrometry. TGA-DSC studies revealed that autoxidation via a radical mechanism
      is dominated by statistical random scission in PS20 and PS80. Thermal initiation
      of radical formation occurs at the polyoxyethylene (POE) as well as the olefin
      sites. In PS80, radical initiation at the olefinic site precedes initiation at
      the POE site, leading to modified degradation profile. Corresponding to these
      results, in aqueous formulations, a surge peroxide content was detected in PS20
      containing samples and in higher concentrations in those containing PS80.
      Hydrolysis in aqueous formulations, as followed by (1)H NMR, was found to have a
      half-life of 5 months at 40 degrees C. On the basis of the obtained results, PSs
      degrade mainly via autoxidation and also via hydrolysis at higher temperatures.
      Further studies are required to investigate on potential effects of degradation
      on surface activity and protein stability in PS-containing formulations.

PMID- 20803574
TI  - Evaluation of predictive models for stable solid solution formation.
AB  - The objective of this study was to evaluate predictive models for stable solid
      solution formation and to find a quick and successful approach for miscibility
      screenings. The results show that the interpretation of the chemical structure
      and the crystallinity by X-ray powder diffraction measurements as well as the
      determination of melting point depressions and melting enthalpies are beneficial
      tools to predict the miscibility of drugs and carriers. A combined approach of
      prediction tools is highly appropriate, as no single technique may yield all the
      required information. Nevertheless, the evaluation of the melting behavior via
      differential scanning calorimetry has the highest impact.

PMID- 20803576
TI  - Under-recognized soft-tissue structures inferior and lateral to the head of the
      clavicle: Anatomy with computed tomography correlation.
AB  - This study was undertaken to provide an anatomical explanation for two soft
      tissue structures anecdotally found on axial computed tomography (CT) scan, which
      are inferior (SI) and lateral (SL) to the head of the clavicle and adjacent to
      the sternoclavicular joint (SCJ). Three sets of cryosection images were reviewed
      to identify the anatomical structures corresponding to SI and SL. To demonstrate
      that SI and/or SL communicate with the SCJ cavity in the living, 312 consecutive
      chest CT scans were assessed for coexistence of SCJ and SI/SL air. To prove that
      under-recognition of SI and SL is due to the use of thick-section CT scan,
      another 50 consecutive chest CT scans were evaluated: visibility of SI and SL,
      and continuity between them on thick (5 mm)-section images were compared with
      those on thin (0.75 mm)-section images. The anterior portions of SI and SL were
      extensions from the SCJ cavity in the cryosection images, with the articular
      cartilage and disc occupying variable volumes of SI. The posterior portions of
      the SI and SL corresponded to the thyroid strap muscles. Air was present in 1 SI,
      6 SLs, and 10 SCJs. Four of five patients with SI or SL air had coexisting SCJ
      air. Thick sections provided significantly poor visibility of SI and SL and
      continuity compared with thin-section images. SI and SL are constant shadows on
      thin-section CT scan, and their anterior and posterior portions represent
      extensions of the SCJ cavity and the strap muscles, respectively. The use of
      thick sections may be responsible for the under-recognition of SI and SL on CT
      scan.

PMID- 20803575
TI  - Poloxamer/cyclodextrin/chitosan-based thermoreversible gel for intranasal
      delivery of fexofenadine hydrochloride.
AB  - To enhance permeation and solubility of an intranasal delivery system of
      fexofenadine hydrochloride (FXD HCl), a new formulation using poloxamer 407
      (P407)/hydroxypropyl-beta-cyclodextrin (HP-beta-CD)-based thermoreversible gels
      with chitosan, was developed. Prepared gels were characterized by gelation
      temperature, viscosity, viscoelasticity, and drug release profile. The in vitro
      permeation study was performed in primary human nasal epithelial cell monolayers
      cultured by air-liquid interface method. The addition of chitosan caused the
      slight elevation of gelation temperature and viscosity-enhancing effect.
      Viscosity enhancement by the incorporation of chitosan caused the retardation of
      drug release from P407 gels in in vitro release test. The in vitro permeation
      profile showed that the increase in chitosan content (0.1% and 0.3%, w/v)
      significantly enhanced the permeation of FXD HCl. After intranasal administration
      of P407/HP-beta-CD-based thermoreversible gels containing 0.1% and 0.3% of
      chitosan in rabbits at 0.5 mg/kg dose, plasma concentrations of FXD HCl were
      significantly higher than those of nasal solutions (p < 0.05). In particular, the
      bioavailability of the optimized thermoreversible gel containing 0.3% chitosan
      was about 18-fold higher than that of the solution type. These results suggested
      the feasibility that thermosensitive gels could be used as an effective dosage
      form to enhance the nasal absorption of FXD HCl.

PMID- 20803577
TI  - Do adolescents know when they need help in the aftermath of war?
AB  - This study examined Israeli Arab and Jewish students' reports on needing help, a
      year after the Second Lebanon War and whether students' requests for support were
      associated with posttraumatic distress. The representative sample included 1,800
      Jewish and 2,351 Arab students, grades 7-11. The questionnaires included items
      regarding (a) exposure to wartime events and other negative life events, (b)
      measures of posttraumatic stress disorder, and (c) needing help. The results
      showed that about 30% of the students reported needing help from any source
      (e.g., parents, peers) in the aftermath of the war. Arab students were more
      likely to report needing help than Jewish students. The students who reported
      needing help experienced higher levels of posttraumatic symptoms.

PMID- 20803578
TI  - Exposure to traumatic events among treatment-seeking, alcohol-dependent women and
      men without PTSD.
AB  - The authors examined lifetime exposure to a range of traumatic events in 106
      abstinent, treatment-engaged (85% residential; 15% outpatient), alcohol-dependent
      women (n = 53) and men without current or lifetime posttraumatic stress disorder.
      Alcohol-dependent women reported greater severity of childhood trauma, but
      similar lifetime exposure to traumatic events compared with men. Alcohol
      dependent women without cocaine abuse or TB (n = 10) reported greater severity of
      childhood trauma than women with (n = 43), and men with (n = 21) or without (n =
      32) cocaine abuse or dependence. Results extend previously observed gender
      differences in trauma histories among alcohol-dependent adults and point to
      potential gender- and substance-specific drug co-addiction effects that may have
      been influenced by trauma exposure.

PMID- 20803579
TI  - Methods for the functionalisation of nanoparticles: new insights and
      perspectives.
AB  - In the field of nanometre-sized drug-delivery systems, a wide range of colloidal
      systems have been created in recent decades. All of the systems have a similar
      global structure, that is, an inner part and an external surface/interface. In
      several applications, the external interface is the support for desired
      properties and the basis of future developments. The engineering of the
      particle's surface is an emerging step in the design of systems at the nanometre
      scale. This review presents and summarises the available techniques with a
      particular attention to recent advances. It is also a base for future works in
      this expanding area of research.

PMID- 20803580
TI  - Ketone-alcohol hydrogen-transfer equilibria: is the biooxidation of halohydrins
      blocked?
AB  - To ensure the quasi-irreversibility of the oxidation of alcohols coupled with the
      reduction of ketones in a hydrogen-transfer (HT) fashion, stoichiometric amounts
      of alpha-halo carbonyl compounds have been employed as hydrogen acceptors. The
      reason that these substrates lead to quasi-quantitative conversions has been
      tacitly attributed to both thermodynamic and kinetic effects. To provide a clear
      rationale for this behavior, we investigate herein the redox equilibrium of a
      selected series of ketones and 2-propanol by undertaking a study that combines
      experimental and theoretical approaches. First, the activity of the (R)-specific
      alcohol dehydrogenase from Lactobacillus brevis (LBADH) with these substrates was
      studied. The docking of acetophenone/(R)-1-phenyethanol and alpha
      chloroacetophenone/(S)-2-chloro-1-phenylethanol in the active site of the enzyme
      confirms that there seems to be no structural reason for the lack of reactivity
      of halohydrins. This assumption is confirmed by the fact that the corresponding
      aluminum-catalyzed Meerwein-Ponndorf-Verley-Oppenauer (MPVO) reactions afford
      similar conversions to those obtained with LBADH, showing that the observed
      reactivity is independent of the catalyst employed. While the initial rates of
      the enzymatic reductions and the IR nu(C=O) values contradict the general belief
      that electron-withdrawing groups increase the electrophilicity of the carbonyl
      group, the calculated DeltaG values of the isodesmic redox transformations of
      these series of ketones/alcohols with 2-propanol/acetone support the
      thermodynamic control of the reaction. As a result, a general method to predict
      the degree of conversion obtained in the HT-reduction process of a given ketone
      based on the IR absorption band of the carbonyl group is proposed, and a strategy
      to achieve the HT oxidation of halohydrins is also shown.

PMID- 20803581
TI  - A doubly signal-amplified DNA detection method based on pre-complexed
      [Ru(bpy)3]2+-doped silica nanoparticles.
AB  - Easy detection: The target DNA in a 10-100 aM range can be detected by pre
      complexed nanoparticles without additional amplification or target labeling. The
      [Ru(bpy)(3)](2+)-doped silica nanoparticles are hybridized to form a complex with
      highly enhanced sensitivity (see scheme). This method will be a significant
      improvement over conventional microarray/fluorescence readout systems.

PMID- 20803582
TI  - Macrocycles as a tool: a facile and one-pot synthesis of silver nanoparticles
      using cucurbituril designed for cancer therapeutics.
AB  - Silver nanoparticles made easy: A simple, effective, and one-pot method toward
      the synthesis of a defined macrocycle-silver nanoparticle system in water has
      been described (see figure). Interestingly, cucurbituril (CB)[7]-protected AgNPs
      showed significantly increased cytotoxicity against MCF-7 and NCI-H358 cancer
      cells, as demonstrated by models in vitro.

PMID- 20803583
TI  - Sox14 is required for transcriptional and developmental responses to 20
      hydroxyecdysone at the onset of drosophila metamorphosis.
AB  - The steroid hormone 20-hydroxyecdysone (20E), by means of a heterodimer
      consisting of two nuclear receptors, the Ecdysone receptor (EcR) and
      Ultraspiracle (Usp), triggers the major developmental transitions in the
      Drosophila life cycle through the regulation of genetic hierarchies. We have
      previously demonstrated that the Sox14 transcription factor is a primary response
      gene to 20E/EcR/Usp complex. In this study, we show that mutations in sox14
      result in prepupal and pupal lethality with animals displaying a multitude of
      defects in 20E developmentally regulated pathways. In addition, through Northern
      blot and microarray analyses of sox14 mutant animals, we demonstrate that Sox14
      is required for the proper expression of 20E- and non-20E-regulated genes at the
      onset of metamorphosis. We also show that the Sox14-regulated gene set correlates
      well with Sox14 expression in a variety of larval and adult tissues. Thus, Sox14
      is a critical transcription factor required for 20E signaling at the onset of
      metamorphosis.

PMID- 20803584
TI  - Corozalic acid: a key okadaic acid biosynthetic precursor with phosphatase
      inhibition activity.
AB  - Toxin precursors: Corozalic acid, a new Ser/Thr protein phosphatase 1 and 2A
      inhibitor that turned out to be a key metabolic intermediate, was isolated from
      cultures of the marine dinoflagellate Prorocentrum belizeanum. Detailed
      spectroscopic analysis and extensive computational calculations revealed its
      structure and conformational behavior. In addition, a comprehensive picture of
      the interactions of corozalic acid with PP1 and PP2A is proposed (see figure) on
      the basis of ab initio, docking and molecular dynamics calculations.

PMID- 20803585
TI  - Synthesis and reactivity of boron-, silicon-, and tin-bridged ansa
      cyclopentadienyl-cycloheptatrienyl titanium complexes (troticenophanes).
AB  - A novel one-pot method was developed for the preparation of [Ti(eta(5)
      C(5)H(5))(eta(7)-C(7)H(7))] (troticene, 1) by reaction of sodium
      cyclopentadienide (NaCp) with [TiCl(4)(thf)(2)], followed by reduction of the
      intermediate [(eta(5)-C(5)H(5))(2)TiCl(2)] with magnesium in the presence of
      cycloheptatriene (C(7)H(8)). The [n]troticenophanes 3 (n=1), 4, 8, 10 (n=2), and
      11 (n=3) were synthesized by salt elimination reactions between dilithiated
      troticene, [Ti(eta(5)-C(5)H(4)Li)(eta(7)-C(7)H(6)Li)]?pmdta (2) (pmdta =
      N,N',N',N'',N''-pentamethyldiethylenetriamine), and the appropriate organoelement
      dichlorides Cl(2)Sn(Mes)(2) (Mes = 2,4,6-trimethylphenyl), Cl(2)Sn(2)(tBu)(4),
      Cl(2)B(2)(NMe(2))(2), Cl(2)Si(2)Me(4), and (ClSiMe(2))(2)CH(2), respectively.
      Their structural characterization was carried out by single-crystal X-ray
      diffraction and multinuclear NMR spectroscopy. The stanna[1]- and
      stanna[2]troticenophanes 3 and 4 represent the first heteroleptic sandwich
      complexes bearing Sn atoms in the ansa bridge. The reaction of 3 with
      [Pt(PEt(3))(3)] resulted in regioselective insertion of the [Pt(PEt(3))(2)]
      fragment into the Sn-C(ipso) bond between the tin atom and the seven-membered
      ring, which afforded the platinastanna[2]troticenophane 5. Oxidative addition was
      also observed upon treatment of 4 with elemental sulfur or selenium, to produce
      the [3]troticenophanes [Ti(eta(5)-C(5)H(4)SntBu(2))(eta(7)-C(7)H(6)SntBu(2))E]
      (6: E=S; 7: E=Se). The B-B bond of the bora[2]troticenophane 8 was readily
      cleaved by reaction with [Pt(PEt(3))(3)] to form the corresponding oxidative
      addition product [Ti(eta(5)-C(5)H(4)BNMe(2))(eta(7)
      C(7)H(6)BNMe(2))Pt(PEt(3))(2)] (9). The solid-state structures of compounds 5, 6,
      and 9 were also determined by single-crystal X-ray diffraction.

PMID- 20803586
TI  - Modulation of the aerobic oxidative polymerization in phenylazomethine dendrimers
      assembling copper complexes.
AB  - The aerobic oxidative polymerization of phenol derivatives can provide
      poly(phenylene oxide)s, which are known as engineering plastics. This oxidation
      can be carried out with atmospheric oxygen molecules as the oxidizing reagent in
      the presence of copper complexes as the catalyst; however, stoichiometric or
      excess amounts of bases are also generally required. By using a phenylazomethine
      dendrimer complexed with several equivalent amounts of copper chloride, the
      additive (base)-free polymerization of 2,6-difluorophenol was successful with a
      very small amount of the catalyst (0.7 mol% of copper for the monomer) because
      the dendrimer was composed of many Schiff base units, affording a base and
      catalyst (copper complex) condensed reaction field. The resulting polymer was
      nearly linear and the molecular weight was very high. When the equimolar amount
      of the copper complex in one dendrimer molecule was increased, the polymer
      obtained under this reaction condition was rather branched, resulting in a higher
      glass transition temperature.

PMID- 20803587
TI  - A highly sensitive and selective turn-on fluorogenic and chromogenic sensor based
      on BODIPY-functionalized magnetic nanoparticles for detecting lead in living
      cells.
AB  - A new fluoro-chromogenic chemosensor based on BODIPY-functionalized
      Fe(3)O(4)@SiO(2) core/shell nanoparticles 1 has been prepared. Chemosensor 1
      exhibits a high affinity and selectivity for Pb(2+) over competing metal ions
      tested. Moreover, confocal microscopy, and flow cytometry experiments established
      that 1 can be used for detecting Pb(2+) levels within living cell.

PMID- 20803588
TI  - A concise total synthesis of amphidinolide T2.
AB  - RCM + AD = T2: In the presence of the C16-methylene group, regioselective ring
      closing metathesis (RCM) formed the (12E)-endocyclic double bond, which underwent
      Os-catalyzed asymmetric dihydroxylation (AD) to give the desired 12,13-diol
      intermediate required for the total synthesis of amphidinolide T2 in 16 linear
      steps in 8.0% overall yield.

PMID- 20803589
TI  - Electroactive organic molecules immobilized onto solid nanoparticles as a cathode
      material for lithium-ion batteries.

PMID- 20803590
TI  - Addressing protein-protein interactions with small molecules: a Pro-Pro dipeptide
      mimic with a PPII helix conformation as a module for the synthesis of PRD-binding
      ligands.

PMID- 20803591
TI  - Putting a positive spin on molecular bridges.

PMID- 20803592
TI  - Light-induced control of protein translocation by the SecYEG complex.

PMID- 20803593
TI  - Disilanyl double-pillared bisanthracene: a bipolar carrier transport material for
      organic light-emitting diode devices.

PMID- 20803594
TI  - Using pressure to provoke the structural transition of metal-organic frameworks.

PMID- 20803596
TI  - Fluorine-enabled cationic gold catalysis: functionalized hydration of alkynes.

PMID- 20803595
TI  - Trapping unstable benzoquinone analogues by coordination to a [(eta(5)
      C(5)Me(5))Ir] fragment and the anticancer activity of the resulting complexes.

PMID- 20803597
TI  - Recombinant EDA or Sonic Hedgehog rescue the branching defect in Ectodysplasin A
      pathway mutant salivary glands in vitro.
AB  - Hypohidrotic ectodermal dysplasia (HED) is characterized by defective ectodermal
      organ development. This includes the salivary glands (SGs), which have an
      important role in lubricating the oral cavity. In humans and mice, HED is caused
      by mutations in Ectodysplasin A (Eda) pathway genes. Various phenotypes of the
      mutant mouse Eda(Ta/Ta), which lacks the ligand Eda, can be rescued by maternal
      injection or in vitro culture supplementation with recombinant EDA. However, the
      response of the SGs to this treatment has not been investigated. Here, we show
      that the submandibular glands (SMGs) of Eda(Ta/Ta) mice exhibit impaired
      branching morphogenesis, and that supplementation of Eda(Ta/Ta) SMG explants with
      recombinant EDA rescues the defect. Supplementation of Edar(dlJ/dlJ) SMGs with
      recombinant Sonic hedgehog (Shh) also rescues the defect, whereas treatment with
      recombinant Fgf8 does not. This work is the first to test the ability of putative
      Eda target molecules to rescue Eda pathway mutant SMGs.

PMID- 20803599
TI  - A mononuclear dysprosium complex featuring single-molecule-magnet behavior.

PMID- 20803600
TI  - Charge separation in wurtzite/zinc-blende heterojunction GaN nanowires.
AB  - The electronic properties of wurtzite/zinc-blende (WZ/ZB) heterojunction GaN are
      investigated using first-principles methods. A small component of ZB stacking
      formed along the growth direction in the WZ GaN nanowires does not show a
      significant effect on the electronic property, whereas a charge separation of
      electrons and holes occurs along the directions perpendicular to the growth
      direction in the ZB stacking. The later case provides an efficient way to
      separate the charge through controlling crystal structure. These results have
      significant implications for most state of the art excitonic solar cells and the
      tuning region in tunable laser diodes.

PMID- 20803598
TI  - Expression, functional, and structural analysis of proteins critical for otoconia
      development.
AB  - Otoconia, developed during late gestation and perinatal stages, couple mechanic
      force to the sensory hair cells in the vestibule for motion detection and bodily
      balance. In the present work, we have investigated whether compensatory
      deposition of another protein(s) may have taken place to partially alleviate the
      detrimental effects of Oc90 deletion by analyzing a comprehensive list of
      plausible candidates, and have found a drastic increase in the deposition of
      Sparc-like 1 (aka Sc1 or hevin) in Oc90 null versus wt otoconia. We show that
      such up-regulation is specific to Sc1, and that stable transfection of Oc90 and
      Sc1 full-length expression constructs in NIH/3T3 cells indeed promotes matrix
      calcification. Analysis and modeling of Oc90 and Sc1 protein structures show
      common features that may be critical requirements for the otoconial matrix
      backbone protein. Such information will serve as the foundation for future
      regenerative purposes.

PMID- 20803601
TI  - Tertiary aminourea-catalyzed enantioselective iodolactonization.

PMID- 20803602
TI  - Subvisible particle counting provides a sensitive method of detecting and
      quantifying aggregation of monoclonal antibody caused by freeze-thawing: insights
      into the roles of particles in the protein aggregation pathway.
AB  - The objective of this study was to evaluate microflow imaging (MFI) as a
      sensitive tool to detect and quantify subvisible particle formation during freeze
      thawing of an IgG(2) monoclonal antibody (mAb). Solutions of the protein
      formulated in 20 mM of histidine buffer (pH 5.5) were subjected to three freeze
      thaw cycles and analyzed by MFI and size-exclusion chromatography (SEC). MFI
      showed increased particle numbers after each freeze-thaw cycle, whereas
      aggregates were not detected by SEC. Estimates of the total mass of particles
      formed revealed that monitoring of particle formation allows for the detection of
      protein aggregates comprising only hundredths of a percent of the total protein
      mass. Furthermore, differences in protein aggregation levels due to different
      formulations or different freeze-thawing protocols were resolved, even though
      protein aggregation could not be detected by SEC. To examine whether SEC and MFI
      based estimations of total aggregate mass were in quantitative agreement, mAb was
      freeze-thawed in phosphate-buffered saline. This process created sufficient level
      of insoluble aggregates to be detected by SEC as a reduction in the monomer peak
      area in the chromatogram. There was good agreement between the loss of monomer
      detected by SEC and the total mass of subvisible particles detected by MFI.

PMID- 20803603
TI  - Effect of poly(3-octylthiophene) doping on the attachment and proliferation of
      osteoblasts.
AB  - The effect of doping P3OT with ferric chloride on the attachment and
      proliferation of MC3T3-E1 osteoblasts is reported. Cell density and area
      correlated strongly with doping concentration: cells were larger and exhibited
      better spreading as doping increased. Cells cultured on undoped P3OT showed a
      decrease in proliferation between 24 and 48 h followed by a recovery after 72 h.
      However, this trend diminished with increasing doping concentration, and
      disappeared completely at the highest dopant level investigated. Analysis of cell
      cell spatial distributions suggested that contact inhibition of proliferation
      occurred similarly on both undoped and doped P3OT. From these results, FeCl(3)
      doping had no significant deleterious effect on attachment or proliferation of
      osteoblasts in vitro.

PMID- 20803604
TI  - Effects of vessel geometric irregularity on dissolution test results.
AB  - Dissolution testing of pharmaceutical products is an important technique used
      extensively for both product development and quality control, but there are many
      variables that can affect dissolution results. In this study, the effect of the
      inner shape of standard 1-L dissolution vessels on drug dissolution results was
      investigated. The geometric dimensions and irregularities of commercially
      available vessels (obtained from four different manufacturers) were examined
      using a three-dimensional video-based measuring machine (VMM). The same analyst,
      dissolution test assembly, and experimental conditions were used for dissolution
      testing involving 10 mg of prednisone tablets (NCDA #2) with dissolution
      apparatus 2 (paddle). Mechanical calibration of the dissolution apparatus was
      performed prior to dissolution testing with each set of vessels. Geometric
      characteristics varied within and among the sets of vessels, but the overall
      averages and standard deviations of dissolution results (six vessels) showed no
      statistical significant differences among the vessel sets. However, some
      dissolution differences were noted when comparing individual vessels. With these
      types of comparisons, the vessel concentricity, sphericity, and radius of sphere
      were found to possibly influence the amount of prednisone dissolved, but flatness
      of vessel flange, cylindricity, and circularity showed no effect on dissolution
      results. The study shows that VMM is a technique that could be used to qualify
      dissolution vessels.

PMID- 20803605
TI  - Understanding size enlargement and hardening of granules on tabletability of
      unlubricated granules prepared by dry granulation.
AB  - The mechanism of loss of "reworkability" or tabletability of dry granulated
      microcrystalline cellulose (MCC) was investigated in relation to both granule
      size enlargement and granule hardness. Slugs of MCC were prepared under three
      pressures (12.5, 37.5, and 93.8 MPa) and tabletability (tensile strength vs.
      pressure) of respective granules (three different sizes) was determined. Nominal
      single granule fracture strength and granule friability were measured. The
      reduction in tabletability was profound for harder granules, which were obtained
      from higher slugging pressure. This is consistent with their ability to resist
      granule fragmentation during tableting. Variation in granule size exhibits
      negligible effect on tabletability for the lowest slugging pressure and only a
      small effect for the middle and highest slugging pressure. This observation is
      again related to different tendency to granule fragmentation during compaction.
      The results suggest that granule-hardening negatively affects tensile strength
      more than that of granule size enlargement for MCC.

PMID- 20803606
TI  - A population-based competing-risks analysis of the survival of patients treated
      with radical cystectomy for bladder cancer.
AB  - BACKGROUND: Patients treated with radical cystectomy represent a very
      heterogeneous group with respect to cancer-specific and other-cause mortality.
      Comorbidities and comorbidity-associated events represent very important causes
      of mortality in those individuals. The authors examined the rates of cancer
      specific and other-cause mortality in a population-based radical cystectomy
      cohort. METHODS: The authors identified 11,260 patients treated with radical
      cystectomy for urothelial carcinoma of the urinary bladder between 1988 and 2006
      within 17 Surveillance, Epidemiology, and End Results registries. Patients were
      stratified into 20 strata according to patient age and tumor stage at radical
      cystectomy. Smoothed Poisson regression models were fitted to obtain estimates of
      cancer-specific and other-cause mortality rates at specific time points after
      radical cystectomy. RESULTS: After stratification according to disease stage and
      patient age, cancer-specific mortality emerged as the main cause of mortality in
      all patient strata. Nonetheless, at 5 years after radical cystectomy, between
      8.5% and 27.1% of deaths were attributable to other-cause mortality. The 3 most
      common causes of other-cause mortality were other malignancies, heart disease,
      and chronic obstructive pulmonary disease. The most prominent effect on cancer
      specific mortality was exerted by locally advanced bladder cancer stages.
      Conversely, age was the main determinant of other-cause mortality. Interestingly,
      even after adjusting for bladder cancer pathologic stage, cancer-specific
      mortality was higher in older individuals than their younger counterparts.
      CONCLUSIONS: The current study provides a valuable graphical aid for prediction
      of cancer-specific and other-cause mortality according to disease stage and
      patient age. It can help clinicians to better stratify the risk-benefit ratio of
      radical cystectomy. Hopefully, these findings will be considered in treatment
      decision making and during informed consent before radical cystectomy.

PMID- 20803608
TI  - Effect of radiotherapy boost and hypofractionation on outcomes in ductal
      carcinoma in situ.
AB  - BACKGROUND: Boost radiotherapy (RT) improves outcomes for patients with invasive
      breast cancer, but whether this is applicable to patients with pure ductal
      carcinoma in situ (DCIS) is unclear. This study examined outcomes from whole
      breast RT, with or without a boost, and the impact of different dose
      fractionation schedules in a population-based cohort of women with pure DCIS
      treated with breast-conserving surgery (BCS). METHODS: Data was analyzed for 957
      subjects diagnosed between 1985 and 1999. RT use was analyzed over time. Ten-year
      Kaplan-Meier local control (LC), breast cancer specific survival (BCSS), and
      overall survival (OS) were compared using the log-rank test. Cox regression
      modeling of LC was performed. RESULTS: Median follow-up was 9.3 years. Of the
      patient cohort 475 (50%) had no RT (NoRT) after BCS, 338 (35%) had RT without a
      partial breast boost (RTNoB), and 144 (15%) had RT with boost (RT + B). Subjects
      with risk factors of local recurrence were more likely to receive RT. Subjects
      receiving adjuvant RT had a trend toward improved LC (15-year LC: NoRT 87%; RTNoB
      94%; RT + B 91%; P = .065). Multivariable analysis showed that RT with or without
      a boost was significantly associated with improved LC (HR, 0.29 and 0.38,
      respectively, compared with NoRT, P = .025), with no difference associated with a
      boost or different dose-fractionation schedules. CONCLUSIONS: Adjuvant RT
      improves local control in patients with DCIS treated with BCS. Hypofractionation
      is as effective as standard fractionation schedules. Boost RT was not associated
      with improved LC compared with whole breast RT alone. Cancer 2011. (c) 2010
      American Cancer Society.

PMID- 20803607
TI  - Outcome of therapy-related acute promyelocytic leukemia with or without arsenic
      trioxide as a component of frontline therapy.
AB  - BACKGROUND: Patients with therapy-related acute promyelocytic leukemia (t-APL)
      have been commonly exposed to topoisomerase inhibitors and may potentially
      benefit from induction regimens omitting anthracyclines. METHODS: Retrospective
      analysis of the outcomes of 29 patients with t-APL who were either treated with
      arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA) or with standard ATRA
      plus anthracycline-based chemotherapy was performed. RESULTS: Prior therapy
      included chemotherapy alone, radiation alone, or a combination of the 2 in 19%,
      33%, and 47% of patients, respectively. The combination of ATO and ATRA (n = 19)
      for induction resulted in a similar remission rate compared with ATRA plus
      chemotherapy (n = 10) (89% vs 70%; P = .35). The median overall survival for the
      patients treated with ATRA plus ATO was not reached compared with that for
      patients treated with ATRA plus chemotherapy (161 weeks; P = .79). CONCLUSIONS:
      In this cohort of t-APL patients, outcomes with ATO and ATRA appeared to be
      comparable to anthracycline-containing induction regimens. This combination may
      be preferable in t-APL patients to avoid any risk of anthracycline-induced
      toxicities.

PMID- 20803609
TI  - Effects of complementary therapies on clinical outcomes in patients being treated
      with radiation therapy for prostate cancer.
AB  - BACKGROUND: This pilot randomized controlled trial (RCT) examined the clinical
      effects of 2 complementary (CAM) therapies, relaxation response therapy (RRT) and
      Reiki therapy, in men being treated with external beam radiotherapy (EBRx) for
      prostate cancer. METHODS: Study participants were randomly assigned to weekly
      RRT, Reiki therapy twice weekly, or wait-list control. Well-validated instruments
      measured anxiety (STAI), depression (CES-D), and quality of life in cancer
      patients (FACT-G) at randomization and 3 subsequent time points. RESULTS: Fifty
      four men were randomized, and 16 of 18 (89%) of RRT and 15 of 18 (83%) of Reiki
      patients completed the intervention protocol. No statistically significant
      difference was found between the RRT, Reiki, and control groups on total scores
      for the STAI, CES-D, or FACT-G instruments at any time point. However, at the end
      of the intervention, significant improvement was found on the emotional well
      being subscale of the FACT-G quality of life scale in the RRT group compared with
      the Reiki and control groups (P = .01). In participants who were classified as
      "anxious" at baseline, statistically significant improvement occurred in the RRT
      group (P = .02), and a positive trend was found in the Reiki group (P = .10).
      CONCLUSIONS: This pilot study documented the feasibility of conducting a RCT of
      CAM therapies in men undergoing EBRx for prostate cancer. Relaxation response
      therapy improved emotional well being and eased anxiety in participants. Reiki
      therapy also had a positive effect in anxious patients. A larger study to verify
      and better define the benefits of these therapies in men with prostate cancer is
      warranted.

PMID- 20803612
TI  - Utilization of prophylactic cranial irradiation in patients with limited stage
      small cell lung carcinoma.
AB  - BACKGROUND: This study reports the adoption of prophylactic cranial irradiation
      (PCI) in patients with limited stage small cell lung carcinoma (LS-SCLC) at
      Princess Margaret Hospital (PMH) and the factors that impact PCI utilization.
      METHODS: A retrospective review was performed on all patients with LS-SCLC
      treated at PMH from 1997 to 2007. Clinical details including the rate of PCI
      utilization were determined and, for patients not receiving PCI, the documented
      reason was recorded. Brain failure free survival (FFS) and overall survival (OS)
      were estimated by the Kaplan-Meier method, comparing patients treated with or
      without PCI. Pearson chi-square test was used to determine factors associated
      with PCI use. RESULTS: Two hundred seven patients were treated for LS-SCLC and
      61.4% (n = 127) of these patients received PCI. The most common documented reason
      for not receiving PCI was patient refusal, typically because of concerns about
      PCI toxicity. Patients older than 65 were significantly less likely to receive
      PCI. Brain FFS and OS rates were significantly higher in patients who received
      PCI. CONCLUSIONS: Not all eligible patients are receiving PCI, despite its
      significant effect on reducing brain metastases and improving OS. Emphasizing the
      benefits of PCI to patients, when discussing potential toxicities, may improve
      utilization.

PMID- 20803611
TI  - Assessment of HER2 gene status in breast carcinomas with polysomy of chromosome
      17.
AB  - BACKGROUND: The current study was performed to determine the impact of polysomy
      17 on the interpretation of HER2 testing of invasive breast carcinomas using
      fluorescent in situ hybridization methods. Current American Society of Clinical
      Oncology/College of American Pathologists guidelines define HER2-positive tumors
      as those with >6 HER2 genes per nucleus or those with HER2/CEP17 (chromosome 17)
      ratio >2.2. These guidelines are potentially contradictory in tumors with
      polysomy of chromosome 17. METHODS: Seventy-two breast carcinoma cases with
      reported polysomy of chromosome 17 (>= 3 CEP17 signals on average) by fluorescent
      in situ hybridization were identified, and the corresponding HER2
      immunohistochemistry was obtained. The HER2 status of the archived samples was
      reviewed, and the tumors were recategorized according to the 2007 American
      Society of Clinical Oncology/College of American Pathologists guidelines.
      RESULTS: The average CEP17 copy number for the group was 4.5 (range, 3.0-10.4).
      Thirty-three (45.8%) cases had >6 copies of HER2 per nucleus. Twenty-one cases
      (29.2%) qualified as HER2 gene amplified using the HER2/CEP17 ratio (>2.2)
      guideline. All these cases had >6 HER2 signals, which represented 63.6% of all
      cases with >6 HER2 signals. HER2 protein expression showed significant positive
      correlations with both HER2 gene copy number and HER2/CEP17 ratio (P < .01, r(s)
      = 0.56 and 0.64, respectively). CONCLUSIONS: Increased CEP17 signals detected in
      invasive breast carcinomas may lead to discordant interpretation of gene
      amplification in a significant proportion of the cases, depending on which
      criterion (ratio vs absolute number) is used for interpretation. However,
      increased gene dosage (>6 HER2 genes or HER2/CEP17 ratio >2.2), regardless of the
      evaluation method, is positively correlated with HER2 protein expression.

PMID- 20803613
TI  - Endoscopic esophageal tumor length: a prognostic factor for patients with
      esophageal cancer.
AB  - BACKGROUND: Pathologic esophageal tumor length (pL) is an independent predictor
      of long-term survival. However, whether patients with longer (high-risk) tumors
      can be identified by endoscopy before surgery has not been established. The
      objective of the current study was to determine the value of endoscopically
      measured tumor length (cL) in predicting overall survival in patients with
      esophageal adenocarcinoma. METHODS: All patients with esophageal adenocarcinoma
      who had undergone resection without neoadjuvant therapy and who had documented
      preoperative endoscopy findings were identified retrospectively by using
      prospectively collected databases at 2 institutions: The University of Texas M.
      D. Anderson Cancer Center (n = 164; training set) and University of Rochester
      Medical Center (n = 109; validation set). Esophageal tumors were assessed
      preoperatively by endoscopy for cL, depth (cT), and lymph node involvement (cN).
      Univariate and multivariate analyses of cL and other standard prognostic factors
      were performed. RESULTS: In the training set, cL was correlated directly with pL
      (Pearson correlation [r] = 0.683; P < .001). Regression tree analyses suggested
      an optimum cutoff point of cL >2 cm to identify patients with decreased long-term
      survival (5-year survival rate: cL >2 cm, 29%; cL <= 2 cm, 78%; P < .001).
      Multivariate Cox regression analysis demonstrated that cL >2 cm was an
      independent risk factor for long-term survival (hazard ratio, 2.3; 95% confidence
      interval, 1.1-4.4; P = .02) even after controlling for age, cT, and cN.
      Validation with the validation dataset confirmed that cL was correlated directly
      with pL (r = 0.657; P < .001) and predicted long-term survival using a cL cutoff
      point of >2 cm (hazard ratio, 2.8; 95% confidence interval, 1.4-5.8; P = .004;
      univariate analysis). CONCLUSIONS: Endoscopic esophageal tumor length was
      identified as an independent predictor of long-term survival and may help to
      identify high-risk patients before they receive cancer-directed therapy.

PMID- 20803614
TI  - Clinical impact of amphiregulin expression in patients with epidermal growth
      factor receptor (EGFR) wild-type nonsmall cell lung cancer treated with EGFR
      tyrosine kinase inhibitors.
AB  - BACKGROUND: In patients with nonsmall cell lung cancer (NSCLC), several studies
      have demonstrated a positive correlation between somatic mutation in the
      epidermal growth factor receptor (EGFR) tyrosine kinase domain and clinical
      outcomes with the use of EGFR tyrosine kinase inhibitors (TKIs). However, some
      patients with wild-type (WT) EGFR also responded to EGFR TKIs and remained
      stable. Recently, amphiregulin (AR) has been suggested as a predictive marker for
      EGFR TKIs in patients with WT EGFR-positive NSCLC. The objective of the current
      study was to evaluate the association between AR expression and the efficacy of
      using EGFR TKIs in the treatment of patients with WT EGFR-positive NSCLC.
      METHODS: Seventy-three patients with WT EGFR-positive NSCLC received treatment
      with gefitinib or erlotinib between May 2005 and December 2008. AR expression was
      assessed by immunohistochemistry. RESULTS: The clinical response to EGFR TKIs was
      reassessed for all patients as follows: 16 of 73 patients had a partial response
      (21.9%), 12 patients had stable disease (16.5%), and 45 patients had progressive
      disease (61.6%). AR expression was positive in 24 of 40 patients (60%). The
      ability to achieve disease control did not differ significantly between AR
      positive patients and AR-negative patients (P = .188). At a median follow-up of
      25.4 months (range, 10.5-53.3 months), progression-free survival was 8.1 weeks in
      AR-positive patients and 4 weeks in AR-negative patients (P = .025), and overall
      survival was significantly longer in AR-positive patients than in AR-negative
      patients (12.2 months vs 4.1 months; P = .001). CONCLUSIONS: The current results
      suggested that patients with WT EGFR-positive NSCLC who have AR-positive tumors
      may benefit clinically from treatment with EGFR TKIs, indicating that AR
      expression may be a potential marker for the selection of EGFR-TKI treatment for
      patients with WT EGFR-positive NSCLC.

PMID- 20803617
TI  - Structural transformations during swelling of polycomplex matrices based on
      countercharged (meth)acrylate copolymers (Eudragit EPO/Eudragit L 100-55).
AB  - With a view to the application in oral controlled drug delivery systems (DDS),
      the design of new interpolyelectrolyte complexes (IPECs) between countercharged
      types of Eudragit EPO (EPO) and Eudragit L 100-55 (L100-55) was investigated. The
      formation and composition of four new IPECs between EPO and L100-55 were
      established by elementary analysis. The structure of the synthesized IPEC was
      investigated using FTIR spectroscopy and modulated-temperature differential
      scanning calorimetry. The binding ratio of a unit molecule of EPO with L100-55
      was found to range between 1:2.75 (Z = 0.36) and 1:0.55 (Z = 1.81) while
      increasing the pH value from 5.5 to 7.0. As a result of electrostatic interaction
      between the copolymer chains, the glass transition temperature of the IPEC
      increased significantly. A large pH-sensitive swelling behavior was observed for
      different structures of the IPECs. The outcome of swelling and diclofenac sodium
      release from the polycomplex matrices confirm that they have great potential to
      be used as a controlled DDS in specified regions of gastrointestinal tract.

PMID- 20803616
TI  - Customized in silico population mimics actual population in docetaxel population
      pharmacokinetic analysis.
AB  - Population pharmacokinetic (PK) analyses have been successfully incorporated into
      drug dosing optimization; however, these analyses necessitate relatively large
      patient cohorts that many clinical trials do not have the luxury of affording. To
      address this problem, we developed an approach that utilizes physiologically
      based pharmacokinetic (PBPK) modeling coupled with Monte Carlo simulation to
      generate a virtual population, complete with associated patient characteristics
      and PK data, for population PK analysis. For this work, we used a previously
      published PBPK model for docetaxel and found that the systemic clearance of this
      drug was significantly affected by blood volume, slowly perfused tissue volume,
      and two liver metabolic parameters--the maximum rate of liver metabolism and the
      Michaelis constant for liver metabolism. These findings, as well as the PK
      variability predictions, are consistent with those previously associated with
      docetaxel clearance in population PK analyses performed with actual patient
      populations, namely plasma protein levels, body size, and hepatic function. Thus,
      this in silico exercise demonstrates the utility of simulation modeling coupled
      to population PK analysis for the estimation of PK variability and the
      identification of patient characteristics that affect a drug's PK in the absence
      of data assembled from large clinical trials.

PMID- 20803618
TI  - Structural abnormalities revealed by magnetic resonance imaging in rats
      prenatally exposed to methylazoxymethanol acetate parallel cerebral pathology in
      schizophrenia.
AB  - Schizophrenia is a highly familial, neurodevelopmental disorder that is
      associated with several neuropsychiatric, psychological, and neuropathological
      features. Although pharmacological animal models of dopaminergic and
      glutamatergic dysfunction have helped advance our understanding of the disease
      biology, there is a clear need for translational models that capture the
      neuropathological and functional manifestations associated with the intermediate
      phenotype and the clinical illness. Neuroimaging of preclinical
      neurodevelopmental approaches such as methylazoxymethanol acetate (MAM) exposure
      may afford a powerful translational tool to establish endpoints with greater
      congruency across animals and humans. Using in vivo volumetric magnetic resonance
      imaging (MRI), manganese-enhanced MRI, and diffusion tensor imaging (DTI), we
      investigated morphological and cytoarchitectural changes of brain structures in
      MAM-exposed rats, a neurodevelopmental model of schizophrenia. Compared to saline
      exposed controls, MAM-exposed rats showed significant enlargement of lateral and
      third ventricles as well as reduced hippocampal volumes, which is consistent with
      findings observed in schizophrenia. In addition, DTI revealed that diffusion
      fractional anisotropy retrieved from corpus callosum and cingulum were
      significantly decreased in MAM-exposed rats, suggesting that demyelination
      occurred in these white-matter fiber tracts. Imaging findings were confirmed by
      conducting histological analysis using hematoxylin and eosin and Luxol fast blue
      stainings. In summary, structural abnormalities resulting from a MAM
      environmental challenge parallel cerebral pathology observed in schizophrenia.
      The MAM model incorporating noninvasive imaging techniques may therefore serve as
      an improved translational research tool for assessing new treatments for
      schizophrenia.

PMID- 20803619
TI  - Distribution of CB2 cannabinoid receptor in adult rat retina.
AB  - Cannabinoid effects are mediated through two receptors, CB1 and CB2. In the
      retina CB1 has been reported in bipolar cells, gabaergic amacrine cells,
      horizontal cells, and inner plexiform layer. CB2 receptor mRNA localization was
      shown in photoreceptors, inner nuclear layer, and ganglion cell layer by using RT
      PCR. The aim of this work was to localize CB2 receptor in the rat retina by using
      immunocytochemistry. Our results showed that CB2 receptor was localized in
      retinal pigmentary epithelium, inner photoreceptor segments, horizontal and
      amacrine cells, cells localized in ganglion cell layer, and in fibers of inner
      plexiform layer. These results are in agreement with studies using RT-PCR and
      provide some additional information about the distribution of CB2 receptor.
      Further studies are needed to clarify the role of this cannabinoid receptor in
      the retina.

PMID- 20803620
TI  - l-Stepholidine-induced excitation of dopamine neurons in rat ventral tegmental
      area is associated with its 5-HT(1A) receptor partial agonistic activity.
AB  - RATIONALE: l-Stepholidine (l-SPD), a tetrahydroprotoberberine alkaloid, possesses
      a pharmacological profile of a D1/5-HT(1A) agonist and a D2 antagonist. This
      unique pharmacological profile makes it a promising novel antipsychotic
      candidate. Preliminary clinical trials and animal experiments suggest that l-SPD
      improves both positive and negative symptoms of schizophrenia without producing
      significant extrapyramidal side effects. To further explore the antipsychotic
      mechanisms of the drug, we studied the effects of l-SPD on the activity of
      dopamine (DA) neurons in the ventral tegmental area (VTA) using in vivo single
      unit recording technique in rats. RESULT: We found that l-SPD increased VTA DA
      neurons firing rate and induced slow oscillation in firing pattern. Moreover, l
      SPD, not clozapine, reversed d-amphetamine-induced inhibition which induced an
      excitation of VTA DA neurons. Furthermore, our data indicated that the excitatory
      effect of l-SPD is associated with its partial agonistic action for the 5-HT(1A)
      receptor since the 5-HT(1A) receptor antagonist WAY100635 could block the l-SPD
      induced excitatory effect. However, activation of 5-HT(1A) receptor alone by
      specific agonist (+/-)-8-Hydroxy-2-(dipropylamino) tetralin (8-OH-DPAT) was
      insufficient to elicit excitation of VTA DA neurons, but the excitation of 8-OH
      DPAT on VTA DA neurons was elicited in the presence of D2-like receptors
      antagonist raclopride. Collectively, these results indicate that l-SPD excited
      VTA DA neurons requiring its D2-like receptors antagonistic activity and 5-HT(1A)
      receptor agonistic activity. CONCLUSION: The present data demonstrate that D2
      receptor antagonist/5-HT(1A) receptor agonistic dual properties modulate
      dopaminergic transmission in a unique pattern that may underlie the different
      therapeutic responses between l-SPD and other atypical antipsychotic drugs.

PMID- 20803621
TI  - Synthesis of new quinoline derivatives as inhibitors of human tumor cells growth.
AB  - A series of new 8-[(2H-tetrazol-5-yl)methoxy]quinoline derivatives, their sugar
      hydrazones, and their N-glycoside derivatives were synthesized. Furthermore, the
      1,2,4-triazole-3-one derivatives 3 and 4 were synthesized from the amidrazone
      derivative 2. Some of the newly prepared compounds demonstrated inhibitory
      effects on the growth of MCF-7 human breast cancer cells as compared with the
      activity of the commonly used anticancer drug, cisplatin. The results of
      antitumor evaluation revealed that compounds 2-5, 8b, and 12 inhibited the growth
      of cancer cells through their effect as free-radical regulators by increasing the
      activity of superoxide dismutase and depletion of intracellular levels of reduced
      glutathione, catalase and glutathione peroxidase activities, accompanied with a
      high production of hydrogen peroxide, nitric oxide, and other free radicals
      causing the killing of tumor cells. The results suggested that the prepared
      compounds possess significant anticancer activity comparable to cisplatin and the
      antitumor activity of these prepared compounds was accompanied with a reduction
      in the levels of protein and nucleic acids.

PMID- 20803622
TI  - Synthesis and antibacterial activity of novel 4''-O-carbamoyl erythromycin-A
      derivatives.
AB  - Novel 4''-O-carbamoyl erythromycin-A derivatives were designed, synthesized, and
      evaluated for their in-vitro antibacterial activities. All of the 4''-O-carbamoyl
      derivatives showed excellent activity against erythromycin-susceptible
      Staphylococcus aureus ATCC25923, Streptococcus pyogenes, and Streptococcus
      pneumoniae ATCC49619. Most of the 4''-O-arylalkylcarbamoyl derivatives displayed
      potent activity against erythromycin-resistant S. pneumoniae encoded by the mef
      gene and greatly improved activity against erythromycin-resistant S. pneumoniae
      encoded by the erm gene or the erm and mef genes. In particular, the 4''-O
      arylalkyl derivatives 4c-4e and 4g were found to possess the most potent activity
      against all the tested erythromycin-susceptible strains, which were comparable to
      those of erythromycin, clarithromycin, or azithromycin. 4''-O-Arylalkyl
      derivatives 4e and 4g were the most effective against erythromycin-resistant S.
      pneumoniae encoded by the mef gene (0.25 and 0.25 microg/mL). 4''-O-Arylalkyl
      derivatives 4a and 4b exhibited significantly improved activity against
      erythromycin-resistant S. pneumoniae encoded by the erm gene. In contrast, the
      4''-O-alkylcarbamoyl derivatives hardly showed improved activity against all the
      tested erythromycin-resistant strains.

PMID- 20803623
TI  - Synthesis, in-vitro cytotoxicity, and a preliminary structure-activity
      relationship investigation of pyrimido[4,5-c]quinoline-1(2H)-ones.
AB  - As part of our ongoing research effort to develop new antimitotic agents based on
      the recently reported pyrimido[4,5-c]quinoline-1(2H)-one ring skeleton, we were
      interested in identifying structural elements that contribute to the cytotoxicity
      of this class of compounds. The effect of several quinoline-ring substituents was
      examined and the new compounds were evaluated in vitro for cytotoxicity against
      three human cancer cell lines namely, lung fibrosarcoma HT-1080, colon
      adenocarcinoma HT-29, and breast carcinoma MDA-MB-231. Most of the compounds
      showed cytotoxic activity in the low micromolar and sub-micromolar range.
      Structure-activity relationship information revealed that a combination of
      electronic and steric factors may be involved. Flow cytometric cell cycle
      analysis performed on HT-1080 cells revealed that the most cytotoxic compounds
      48, 50, 54, 59, and 63 inhibit the S-phase and arrest the cells in the G2/M phase
      of the cell cycle suggesting an antimitotic action of these compounds.

PMID- 20803624
TI  - Original and efficient synthesis of D-cycloserine.
AB  - A simple pathway for the preparation of D-cycloserine is presented. The
      intermediates and D-cycloserine were characterized by FT-IR, (1)H-NMR spectra and
      elemental analysis. D-Cycloserine can inhibit the growth of Mycobacterium
      tuberculosis and can be used as a second-line drug for the treatment of
      tuberculosis, especially for the use in developing countries.

PMID- 20803629
TI  - Impact evaluation of India's 'Yeshasvini' community-based health insurance
      programme.
AB  - Using propensity score matching techniques, the study evaluates the impact of
      India's Yeshasvini community-based health insurance programme on health-care
      utilisation, financial protection, treatment outcomes and economic well-being.
      The programme offers free out-patient diagnosis and lab tests at discounted rates
      when ill, but, more importantly, it covers highly catastrophic and less
      discretionary in-patient surgical procedures. For its impact evaluation, 4109
      randomly selected households in villages in rural Karnataka, an Indian state,
      were interviewed using a structured questionnaire. A comprehensive set of
      indicators was developed and the quality of matching was tested. Generally, the
      programme is found to have increased utilisation of health-care services, reduced
      out-of-pocket spending, and ensured better health and economic outcomes. More
      specifically, however, these effects vary across socio-economic groups and
      medical episodes. The programme operates by bringing the direct price of health
      care down but the extent to which this effectively occurs across medical episodes
      is an empirical issue. Further, the effects are more pronounced for the better
      off households. The article demonstrates that community insurance presents a
      workable model for providing high-end services in resource-poor settings through
      an emphasis on accountability and local management.

PMID- 20803630
TI  - An impact evaluation of the Safe Motherhood Program in China.
AB  - Using 11 years of county-level panel data, fixed effect models are estimated to
      evaluate the impact of the Safe Motherhood (SM) Program in China. Propensity
      score matching is used to select comparable factual and counterfactual counties.
      Out of 2013 counties in China, 283 are selected for the treatment group and 1051
      for the control group. The results support the causal relationship between the
      program and its targeted outcomes and the partial effects increases as years of
      exposure in the program: 7 years' treatment of the program increases hospital
      delivery rate by 3.992 per 100 live births and decreases Maternal mortality ratio
      (MMR) due to hemorrhage by 10.229 per 100,000 live births. Further modeling
      supports the conclusion that the program reduces MMR by enhancing MCH care. With
      an average annual incremental unit cost for the program of about 318.0 thousand
      RMB (39.8 thousand USD) per county, we conclude that the SM Program is effective
      in reducing MMR through the enhancement of hospital delivery.

PMID- 20803631
TI  - Evaluating the impact of community-based health interventions: evidence from
      Brazil's Family Health Program.
AB  - This paper analyzes the direct and indirect impacts of Brazil's Family Health
      Program, using municipality level mortality data from the Brazilian Ministry of
      Health, and individual level data from the Brazilian household survey. We
      estimate the effects of the program on mortality and on household behavior
      related to child labor and schooling, employment of adults, and fertility. We
      find consistent effects of the program on reductions in mortality throughout the
      age distribution, but mainly at earlier ages. Municipalities in the poorest
      regions of the country benefit particularly from the program. For these regions,
      implementation of the program is also robustly associated with increased labor
      supply of adults, reduced fertility, and increased school enrollment. Evidence
      suggests that the Family Health Program is a highly cost-effective tool for
      improving health in poor areas.

PMID- 20803632
TI  - Perceived benefits and barriers to joint protection among people with rheumatoid
      arthritis and occupational therapists. A mixed methods study.
AB  - BACKGROUND: Deciding whether or not to perform a health behaviour is an active
      decision-making process which has an impact on current and future behaviour and
      can be influenced by the beliefs both of patients and their healthcare
      professionals. The aim of this study was to explore rheumatoid arthritis (RA)
      patients' and occupational therapists' (OTs) perceptions of the benefits of and
      barriers to performing joint protection (JP). METHODS: A mixed methods design was
      used. Questionnaires applied a theoretical framework of key themes to assess the
      relevance of JP benefits and barriers both to people with RA and OTs. Focused
      interviews with people with RA then enabled data triangulation. Investigator
      triangulation was used to check the validity of data interpretation. FINDINGS:
      Ten people with RA and nine OTs participated. From the questionnaires, both
      groups agreed that highly relevant key themes for JP benefits were physical well
      being, potential benefit and personal control. By contrast, the three key themes
      for JP barriers - negative attitude of others, negative impact on others and
      taking time from other things - were relevant for the majority of the OTs but not
      patients. The interviews enabled an understanding of the meaning behind RA
      patients' ratings, particularly their differences from OTs. People with RA
      explained JP benefits, and disease acceptance had altered some initial barriers
      into perceived benefits over time. CONCLUSIONS: Emphasizing benefits and
      identifying individually relevant barriers could be an important communication
      strategy for OTs in understanding patients' rationale for whether or not to adopt
      JP methods.

PMID- 20803633
TI  - Do hypermobile subjects without pain have alteration to the feedback mechanisms
      controlling the shoulder girdle?
AB  - OBJECTIVES: It has been reported that hypermobile subjects have proprioceptive
      deficits. However, it remains unclear whether pain-free subjects with
      hypermobility also have deficits. METHODS: Ten subjects with hypermobility and
      nine without hypermobility were recruited following ethical approval and informed
      consent. Shoulder mobility, joint position sense (JPS) and a reflex of trapezius
      evoked from arm afferents were compared. RESULTS: There was greater shoulder
      mobility in the hypermobile group (p = 0.004). There were no differences in
      shoulder JPS between the groups (p = 0.27), although, the hypermobile group
      displayed a larger degree of variability (p = 0.014). Finally, there were no
      differences in the latency of upper and lower trapezius reflexes evoked from arm
      afferents (p = 0.86 and 0.98, respectively). CONCLUSIONS: In a group of people
      with hypermobility without shoulder problems, there was no difference in either
      shoulder JPS or reflex latency when compared with a non- hypermobile group. The
      relevance of pain to proprioceptive deficits is discussed.

PMID- 20803634
TI  - Manifestations of systemic sclerosis necessitate a holistic approach to patient
      care: a case report.
AB  - This case describes a young woman with manifestations of systemic sclerosis in
      multiple organ systems and her guidance through two successful pregnancies. This
      case emphasizes that patients with severe diseases are not just clinical cases;
      they each have unique needs and concerns beyond the physical manifestations of
      their disease. Young patients can be a particular challenge due to their need for
      independence. Communication is the key. Textbook advice in this case was that the
      risks posed by pregnancy were too great; however, a holistic approach, including
      frank discussion and much practical support, enabled the patient to make informed
      choices about her life, with a successful outcome.

PMID- 20803635
TI  - Can the application of control theory assist patient management in rheumatoid
      arthritis?
AB  - Supporting patient self-management is an important part of the care of patients
      with rheumatoid arthritis (RA) but patients vary in their capacity and
      willingness to manage their illness and may feel overwhelmed by the challenge of
      controlling the impact on their life. This paper discusses the value and
      importance of control theory and how it might be applied to enhance patients'
      self-management. Not only does it offer a means of identifying those who might
      have greatest difficulty in managing their illness, but it also points the way to
      effective interventions.

PMID- 20803636
TI  - The value of the nurse specialists' role: Pandora initial findings.

PMID- 20803640
TI  - Tetrasomy 18p: report of the molecular and clinical findings of 43 individuals.
AB  - Thus far, the phenotype of tetrasomy 18p has been primarily delineated by
      published case series and reports. Findings reported in more than 25% of these
      cases include neonatal feeding problems, growth retardation, microcephaly,
      strabismus, muscle tone abnormalities, scoliosis/kyphosis, and variants on brain
      MRI. Developmental delays and cognitive impairment are universally present. The
      purpose of this study was to more fully describe tetrasomy 18p at both the
      genotypic and the phenotypic levels. Array CGH was performed on 43 samples from
      individuals with tetrasomy 18p diagnosed via routine karyotype. The medical
      records of 42 of these 43 individuals were reviewed. In order to gain additional
      phenotypic data, 31 individuals with tetrasomy 18p underwent a series of clinical
      evaluations at the Chromosome 18 Clinical Research Center. Results from the
      molecular analysis indicated that 42 of 43 samples analyzed had 4 copies of the
      entire p arm of chromosome 18; one individual was also trisomic for a section of
      proximal 18q. The results of the medical records review and clinical evaluations
      expand the phenotypic description of tetrasomy 18p to include neonatal jaundice
      and respiratory distress; recurrent otitis media; hearing loss; seizures;
      refractive errors; constipation and gastroesophageal reflux; cryptorchidism;
      heart defects; and foot anomalies. Additional findings identified in a small
      number of individuals include hernias, myelomeningocele, kidney defects, short
      stature, and failure to respond to growth hormone stimulation testing.
      Additionally, a profile of dysmorphic features is described. Lastly, a series of
      clinical evaluations to be considered for individuals with tetrasomy 18p is
      suggested.

PMID- 20803641
TI  - Understanding attitudes toward people with Down syndrome.
AB  - Understanding attitudes of the public toward people with Down syndrome is
      important because negative attitudes might create barriers to social integration,
      which can affect their success and quality of life. We used data from two 2008
      U.S. surveys (HealthStyles(c) survey of adults 18 years or older and
      YouthStyles(c) survey of youth ages 9-18) that asked about attitudes toward
      people with Down syndrome, including attitudes toward educational and
      occupational inclusion and toward willingness to interact with people with Down
      syndrome. Results showed that many adults continue to hold negative attitudes
      toward people with Down syndrome: A quarter of respondents agreed that students
      with Down syndrome should go to special schools, nearly 30% agreed that including
      students with Down syndrome in typical educational settings is distracting, and
      18% agreed that persons with Down syndrome in the workplace increase the chance
      for accidents. Negative attitudes were also held by many youth: 30% agreed that
      students with Down syndrome should go to separate schools, 27% were not willing
      to work with a student with Down syndrome on a class project, and nearly 40%
      indicated they would not be willing to spend time with a student with Down
      syndrome outside of school. Among both adult and youth, female sex and
      respondents with previous relationships with people with Down syndrome were
      consistently associated with more positive attitudes. These results may be
      helpful in the development of educational materials about Down syndrome and in
      guiding policies on educational and occupational inclusion.

PMID- 20803642
TI  - Long-term parental psychological distress among parents of children with a
      malformation--a prospective longitudinal study.
AB  - We previously reported that prenatal diagnosis of malformations is associated
      with increased parental psychological distress after birth compared to distress
      in parents with postnatal diagnosis. We have now extended our earlier study to
      include a long-term follow-up of mothers and fathers 9 years after birth.
      Psychological responses were measured by General Health Questionnaire (GHQ-28),
      State Anxiety Inventory (STAI-X1), and Impact of Event Scale (IES) in 118 mothers
      and 100 fathers of 124 children with malformations 0-7 days (T1), 6 weeks (T2), 6
      months (T3), and 9 years postpartum (T4). At T4 we observed no significant
      differences in psychological responses comparing parents with and without
      prenatal foreknowledge of their child's malformation. At T4 30.2% and 27.8% of
      the parents reported clinically important psychological distress and clinically
      important state anxiety, respectively. Intrusive stress decreased from T1 to T3,
      but increased significantly from T3 to T4. At T4 25.6% of the parents reported
      severe intrusive stress, with a higher proportion among mothers than fathers
      (32.8% vs. 17.2%, P = 0.029). In the multivariate analysis, unemployment
      predicted clinically important psychological distress at T4, whereas, clinically
      important state anxiety at T4 was predicted by low educational level. This study
      shows that prenatal diagnosis is associated with significantly increased
      psychological distress in the acute postnatal phase. However, there was no long
      term increase in psychological distress among parents with prenatal foreknowledge
      of their child's malformation. The significantly increased intrusive stress at 9
      year follow-up might reflect long-term challenges related to having a child with
      a malformation.

PMID- 20803643
TI  - Two missense mutations of the IRF6 gene in two Japanese families with popliteal
      pterygium syndrome.
AB  - Mutations in the interferon regulatory factor 6 gene (IRF6) cause either
      popliteal pterygium syndrome (PPS) or Van der Woude syndrome (VWS), allelic
      autosomal dominant orofacial clefting conditions. To further investigate the IRF6
      mutation profile in PPS, we performed mutation analysis of patients from two
      unrelated Japanese families with PPS and identified mutations in IRF6: c.251G>T
      (R84L) and c.1271C>T (S424L). We also found R84L, which together with previous
      reports on R84 mutations, provided another line of evidence that both syndromes
      could result from the same mutation probably under an influence of a modifier
      gene(s). This supports the idea that the R84 residue in the DNA binding domain of
      IRF6 is a mutational hot spot for PPS. A luciferase assay of the S424L protein in
      the other family demonstrated that the mutation decreased the IRF6
      transcriptional activity significantly to 6% of that of the wild-type. This
      finding suggests that the C-terminus region of IRF6 could have an important
      function in phosphorylation or protein interaction. To our knowledge, this is the
      first report of mutations observed in Japanese PPS patients.

PMID- 20803644
TI  - Molecular and neuroimaging findings in pontocerebellar hypoplasia type 2 (PCH2):
      is prenatal diagnosis possible?
AB  - The pontocerebellar hypoplasias (PCH) are a group of early-onset, autosomal
      recessive disorders resulting in abnormal growth and function of the brainstem
      and cerebellum. PCH type 2 (PCH2) is characterized by respiratory and feeding
      difficulties at birth, extrapyramidal dyskinesia, severe developmental
      impairment, progressive microcephaly and frequent death in childhood.
      Neuropathologic findings include diffuse cerebral gliosis with white matter
      changes, hypoplastic pons with depletion of neurons in the pontine nuclei,
      hypoplastic cerebellar hemispheres due to short cerebellar folia with poor
      branching, segmental loss of dentate, inferior olivary, and ventral pontine
      nuclei, and near absence of transverse pontine fibers with preservation of long
      fiber tracts and spinal anterior horn cells. On brain imaging, the cerebellar
      hemispheres appear very flat, and are more severely involved than the vermis.
      Most patients with PCH2 have mutations in TSEN54, with occasional mutations found
      in TSEN34 or TSEN2, genes that encode subunits of tRNA splicing endonuclease.
      Although this is a congenital disorder of pontocerebellar dysgenesis with fetal
      onset of neurodegeneration and symptoms at birth, prenatal imaging is unreliable
      in diagnosing this disorder in utero. We report on IVF dizygous twins with
      detailed prenatal imaging that failed to reveal any cerebellar abnormalities.
      Direct sequence analysis of TSEN54 showed homozygosity for c.919G>T, the common
      founder mutation in most PCH2 patients, and both parents were heterozygous for
      this mutation. We found no evidence of cerebellar dysgenesis on prenatal
      ultrasounds, but MRI tractography showed absence of pontine crossing fibers, a
      unique feature that might be useful for prenatal diagnosis of this condition.

PMID- 20803645
TI  - Chimerism resulting from parthenogenetic activation and dispermic fertilization.
AB  - Whole-body human chimerism is the result of two zygotes giving rise to one
      individual, and is a rarely detected condition. We have studied the molecular
      background and discuss the likely mechanism for the chimerism in a patient with a
      46,XX/47,XY,+14 karyotype and ambiguous genitalia, cryptorchidism, pigment
      anomalies, and normal psychomotor development. We have used karyotyping,
      interphase-FISH and array-CGH analysis as well as molecular analysis of
      polymorphic markers from 48 loci in order to define the origin and percentage of
      47,XY,+14 cells in different tissues. Based on the findings of two paternal
      alleles and the detection of homozygous maternal alleles without evidence of
      crossing-over, and the fact that four alleles were never detected, our results
      indicate that the chimerism in our patient is the result of dispermic
      fertilization of a parthenogenetically activated oocyte. Our report underlines
      that cytogenetic findings suggesting mosaicism might actually indicate chimerism
      as an underlying mechanism in patients. It also highlights the difficulties in
      predicting the clinical outcome in patients with genetic aberrations in mosaic or
      chimeric form.

PMID- 20803646
TI  - Emberger syndrome-primary lymphedema with myelodysplasia: report of seven new
      cases.
AB  - Four reports have been published on an association between acute myeloid
      leukaemia (AML) and primary lymphedema, with or without congenital deafness. We
      report seven new cases, including one extended family, confirming this entity as
      a genetic syndrome. The lymphedema typically presents in one or both lower limbs,
      before the hematological abnormalities, with onset between infancy and puberty
      and frequently affecting the genitalia. The AML is often preceded by pancytopenia
      or myelodysplasia with a high incidence of monosomy 7 in the bone marrow (five
      propositi and two relatives). Associated anomalies included hypotelorism,
      epicanthic folds, long tapering fingers and/or neck webbing (four patients),
      recurrent cellulitis in the affected limb (four patients), generalized warts (two
      patients), and congenital, high frequency sensorineural deafness (one patient).
      Children with lower limb and genital lymphedema should be screened for
      hematological abnormalities and immunodeficiency.

PMID- 20803647
TI  - Supernumerary impacted teeth in a patient with SOX2 anophthalmia syndrome.
AB  - SOX2 anophthalmia syndrome characteristically presents as anophthalmia or
      microphthalmia, with various extraocular symptoms, such as hypogonadotropic
      hypogonadism, brain anomaly, and esophageal abnormalities. In this report, we
      describe a patient with SOX2 anophthalmia syndrome complicated with a dental
      anomaly, multiple supernumerary impacted teeth, and persistence of deciduous
      teeth. Multiple supernumerary teeth are usually not solitary symptoms, but
      indicate systemic syndrome such as cleidocranial dysplasia. In odontogenesis,
      many transcriptional factors, such as BMPs, FGFs, and Wnts, play significant
      roles and SOX2 is known to interact with some of them. The role of SOX2 in dental
      development remains unknown, however, multiple supernumerary teeth can be
      considered as extraocular symptoms of SOX2 anophthalmia syndrome, rather than the
      coincidence of two rare diseases.

PMID- 20803648
TI  - Megalencephaly, mega corpus callosum, and complete lack of motor development:
      delineation of a rare syndrome.
AB  - Unlike atrophy of the corpus callosum (CC), callosal hypertrophy is a rare
      neuroimaging finding with only few reported patients. The "megalencephaly, mega
      CC, and complete lack of motor development" syndrome is morphologically
      characterized by generalized megalencephaly, a thickened CC, and extensive
      polymicrogyria causing a pachygyric appearance. We report on the fifth patient
      showing this rare syndrome, a 3-year-old girl displaying the typical neuroimaging
      features. Clinically she showed a severely impaired motor, mental, and speech
      development with marked muscular hypotonia but no dysmorphic facial signs. She
      also retained the ability to move by rolling sidewards so that complete lack of
      motor development may not be a consistent feature.

PMID- 20803649
TI  - Identification of a submicroscopic 3.2 Mb chromosomal 16q12.2-13 deletion in a
      child with short stature, mild developmental delay, and craniofacial anomalies,
      by high-density oligonucleotide array-a recognizable syndrome.
AB  - Interstitial deletion of 16q has emerged into a recognizable pattern of
      congenital malformation. We report on a 9-year-old boy with short stature,
      psychomotor retardation, high forehead, broad flat nasal bridge, hypertelorism,
      cup-shaped ears, short neck, and a normal karyotype. Using high-density
      oligonucleotide array chip (Affymetrix 6.0) to perform parental and proband
      samples concurrently on three chips and interpreted as a trio set, a de novo 3.2
      Mb deletion from bands q12.2 to q13 on chromosome 16 (from 52.08 to 55.3 Mb) of
      paternal origin was identified. The deletion was confirmed by quantitative
      genomic PCR and the break points were defined by junction PCR. Our study
      demonstrated the power of high-density oligonucleotide array chip in identifying
      novel submicroscopic deletions that were not detectable using G-banding
      cytogenetic technology. Furthermore, our result narrowed down the critical region
      for craniofacial features in interstitial 16q11.2-q13 deletion syndrome. In
      patients who have high forehead, broad flat nasal bridge, hypertelorism, cup
      shaped ears, short neck and short stature, high-density array should be included
      in initial work up.

PMID- 20803650
TI  - Wiedemann-Steiner syndrome: three further cases.
AB  - We describe three patients with a syndrome comprising arched, thick eyebrows,
      hypertelorism, narrow palpebral fissures, broad nasal bridge and tip, long
      philtrum, thin upper lip, stubby hands and feet, hirsutism, and severe
      psychomotor retardation. These patients expand the phenotype of the Wiedemann
      Steiner syndrome and delineate it as an entity.

PMID- 20803651
TI  - Central nervous system abnormalities in two cases with neonatal Marfan syndrome
      with novel mutations in the fibrillin-1 gene.

PMID- 20803652
TI  - Constitutional telomeric dysfunction in an azoospermic male with extensive
      telomeric association.

PMID- 20803653
TI  - Imprinted genes and human disease.
AB  - This issue of Seminars of Medical Genetics features a series of articles on human
      disorders caused by the dysregulation of imprinted genes. At the outset, there is
      a review of the general mechanisms by which genomic imprinting is normally
      regulated followed by an exploration of the clinical and molecular aspects of
      human imprinting disorders. As we enter an era of bioinformatics and genome-wide
      analyses with increasing access to high density microarrays and next generation
      sequencing, it is becoming apparent that the concept of a single mutation or
      epimutation leading to a disease is outdated. The role of the clinician will
      become increasingly important, in concert with these molecular advances, in terms
      of evaluating phenotypic variation to further our understanding of imprinting
      disorders. Such investigations will benefit children and families as we become
      better able to define recurrence risk, predict phenotype, and tailor medical
      management.

PMID- 20803654
TI  - Mechanisms of imprint dysregulation.
AB  - Genomic imprinting is an epigenetic process by which the male and the female germ
      line confer specific marks (imprints) onto certain gene regions, so that one
      allele of an imprinted gene is active and the other allele is silent. Genomic
      imprints are erased in primordial germ cells, newly established during later
      stages of germ cell development, and stably inherited through somatic cell
      divisions during postzygotic development. Defects in imprint erasure,
      establishment, or maintenance result in a paternal chromosome carrying a maternal
      imprint or in a maternal chromosome carrying a paternal imprint. A wrong imprint
      leads to activation of an allele that should be silent or silencing of an allele
      that should be active. Since the dosage of imprinted genes is very important for
      development and growth, imprinting defects lead to specific diseases. Imprinting
      defects can occur spontaneously without any DNA sequence change (primary
      imprinting defect) or as the result of a mutation in a cis-regulatory element or
      a trans-acting factor (secondary imprinting defect). The distinction between
      primary and secondary imprinting defects is important for assessing the
      recurrence risk in affected families.

PMID- 20803655
TI  - Uniparental disomy and human disease: an overview.
AB  - Uniparental disomy (UPD) refers to the situation in which both homologues of a
      chromosomal region/segment have originated from only one parent. This can involve
      the entire chromosome or only a small segment. As a consequence of UPD, or
      uniparental duplication/deficiency of part of a chromosome, there are two types
      of developmental risk: aberrant dosage of genes regulated by genomic imprinting
      and homozygosity of a recessive mutation. UPD models generated by reciprocal and
      Robertsonian translocation heterozygote intercrosses have been a powerful tool to
      investigate genomic imprinting in mice, whereas novel UPD patients such as those
      with cystic fibrosis and Prader-Willi syndrome, triggered the clarification of
      recessive diseases and genomic imprinting disorders in human. Newly developed
      genomic technologies as well as conventional microsatellite marker methods have
      been contributing to the functional and mechanistic investigation of UPD, leading
      to not only the acquisition of clinically valuable information, but also the
      further clarification of diverse genetic processes and disease pathogenesis.

PMID- 20803656
TI  - Transient neonatal diabetes mellitus type 1.
AB  - Transient neonatal diabetes mellitus type 1 (TNDM1) is a rare but remarkable form
      of diabetes which presents in infancy, resolves in the first months of life, but
      then frequently recurs in later life. It is caused by overexpression of the
      imprinted genes PLAGL1 and HYMAI on human chromosome 6q24. The expression of
      these genes is normally restricted to the paternal allele as a result of maternal
      DNA methylation. TNDM1 is not associated with mutation of PLAGL1 or HYMAI, but
      rather with their overexpression via uniparental disomy, chromosome duplication,
      or relaxation of imprinting. Study of patients with TNDM1 has provided valuable
      insights into the causes of imprinting disorders. Over half of patients with
      maternal hypomethylation at the TNDM1 locus have additional hypomethylation of
      other maternally methylated imprinted genes throughout the genome, and the
      majority of these patients have mutations in the transcription factor ZFP57.
      TNDM1 with maternal hypomethylation has also been observed in patients conceived
      by assisted reproduction, and in discordant monozygotic twins. The variable
      clinical features of TNDM1 may be associated with variation in the nature of the
      underlying epigenetic and genetic mutations, and future study of this disorder is
      likely to yield further insights not only into the biological mechanisms of
      imprinting, but also into the contribution of epigenetics to diabetes.

PMID- 20803657
TI  - Beckwith-Wiedemann syndrome.
AB  - Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder characterized by
      overgrowth, tumor predisposition, and congenital malformations. Approximately 85%
      of reported BWS cases are sporadic, while the remaining 15% are familial. BWS is
      caused by epigenetic or genomic alterations which disrupt genes in one or both of
      the two imprinted domains on chromosome 11p15.5. In each domain, an imprinting
      center regulates the expression of imprinted genes in cis. Normally in domain 1,
      insulin-like growth factor 2 (IGF2) and the untranslated mRNA H19 are
      monoallelically expressed. In BWS, increased expression of IGF2 occurs via
      several mechanisms. In domain 2, CDKN1C, a growth repressor, and an untranslated
      RNA, KCNQ1OT1, are normally expressed monoallelically. In cases of BWS, several
      mechanisms result in reduced expression of CDKN1C. Recent reports of BWS cases
      have identified mutations outside the chromosome 11p15.5 critical region, thereby
      broadening the challenges in the diagnosis and genetic counseling of individuals
      and families with BWS.

PMID- 20803658
TI  - Russell-Silver syndrome.
AB  - In comparison to Prader-Willi or Angelman syndrome, Russell-Silver syndrome (RSS)
      is a relatively "young" imprinting disorder. This congenital disease is
      characterized by intrauterine and postnatal growth retardation, relative
      macrocephaly, a typical triangular face, asymmetry, and further less constant
      characteristic features. Genetic and epigenetic disturbances can meanwhile be
      detected in approximately 50% of patients with typical RSS features. Up to 5% of
      patients carry a maternal uniparental disomy of chromosome 7 (UPD(7)mat), at
      least 44% show hypomethylation in the chromosome 11p15 imprinting center 1 (IC).
      In 1-2% of RSS patients, (sub)microscopic chromosomal aberrations can be
      observed. The diagnostic workup should therefore include methylation/genomic
      testing for chromosome 11p15, UPD(7)mat analysis and molecular karyotyping. The
      recurrence risk is generally low in RSS but it can be strongly increased in cases
      of familial epimutations or a chromosomal rearrangement. Interestingly, in
      approximately 7% of cases with chromosome 11p15 hypomethylation, hypomethylation
      of additional imprinted loci can be detected. Clinically, patients with
      hypomethylation at multiple loci do not differ from those with isolated 11p15
      hypomethylation whereas the UPD(7)mat patients generally show a milder phenotype.
      Nevertheless, (epi)genotype-phenotype correlations are still evolving.
      Furthermore, the pathophysiological mechanisms resulting in the RSS phenotype
      still remain unknown despite the recent progress in deciphering the molecular
      defects associated with this condition.

PMID- 20803659
TI  - Prader-Willi syndrome and Angelman syndrome.
AB  - Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two distinct
      neurogenetic disorders in which imprinted genes on the proximal long arm of
      chromosome 15 are affected. Although the SNORD116 gene cluster has become a prime
      candidate for PWS, it cannot be excluded that other paternally expressed genes in
      the chromosomal region 15q11q13 contribute to the full phenotype. AS is caused by
      a deficiency of the UBE3A gene, which in the brain is expressed from the maternal
      allele only. The most frequent genetic lesions in both disorders are a de novo
      deletion of the chromosomal region 15q11q13, uniparental disomy 15, an imprinting
      defect or, in the case of AS, a mutation of the UBE3A gene. Microdeletions in a
      small number of patients with PWS and AS have led to the identification of the
      chromosome 15 imprinting center (IC). The IC consists of two critical elements,
      which act in cis to regulate imprinting in the whole chromosome 15q11q13
      imprinted domain.

PMID- 20803660
TI  - Imprinting on chromosome 20: tissue-specific imprinting and imprinting mutations
      in the GNAS locus.
AB  - The GNAS locus on chromosome 20q13.11 is the archetypal complex imprinted locus.
      It comprises a bewildering array of alternative transcripts determined by
      differentially imprinted promoters which encode distinct proteins. It also
      provides the classic example of tissue-specific imprinted gene expression, in
      which the canonical GNAS transcript coding for Gsalpha is expressed predominantly
      from the maternal allele in a set of seemingly unrelated tissues. Functionally,
      this rather obscure imprinting is nevertheless of considerable clinical
      significance, as it dictates the nature of the disease caused by inactivating
      mutations in Gsalpha, with end organ hormone resistance specifically on maternal
      transmission (pseudohypoparathyroidism type 1a, PHP1a). In addition, there is a
      bona fide imprinting disorder, PHP1b, which is caused specifically by DNA
      methylation defects in the differentially methylated regions (DMRs) that
      determine tissue-specific monoallelic expression of GNAS. Although the genetic
      defect in PHP1a and the disrupted imprinting in PHP1b both essentially result in
      profound reduction of Gsalpha activity in tissues with monoallelic GNAS
      expression, and despite a growing awareness of the overlap in these two
      conditions, there are important pathophysiological differences between the two
      whose basis is not fully understood. PHP1b is one of the only imprinted gene
      syndromes in which cis-acting mutations have been discovered that disrupt
      methylation of germline-derived imprint marks; such imprinting mutations in GNAS
      are helping to provide important new insights into the mechanisms of imprinting
      establishment generally.

PMID- 20803662
TI  - Impact of bacterial meningitis-associated conditions on pediatric inpatient
      resource utilization.
AB  - OBJECTIVE: To define the epidemiology of systemic complications and focal
      infections associated with bacterial meningitis and quantify how the presence of
      such complications affects in-hospital healthcare resource utilization. METHODS:
      Retrospective cohort study using administrative data from 27 children's
      hospitals. Children <18 years of age diagnosed with bacterial meningitis from
      2001 to 2006 were eligible. The primary exposure of interest was the presence of
      a bacterial meningitis-associated condition, classified as either systemic
      complications (eg, sepsis), associated focal infections (eg, pneumonia) or both.
      The primary outcomes were total in-hospital charges and length of stay (LOS).
      RESULTS: A total of 574 of 2319 (25%) of children had a systemic complication or
      an associated focal infection. Compared with children without complications, in
      hospital charges were significantly higher in children with systemic
      complications (136% increase), associated focal infections (118% increase), and
      both conditions (351% increase). LOS was also significantly increased in those
      with systemic complications (by 72%), associated focal infections (by 78%), or
      both conditions (by 211%). The presence of systemic complications was more common
      in younger children while the presence of an associated focal infection was more
      common in older children. CONCLUSIONS: Children with bacterial meningitis often
      have additional morbidity due to systemic complications or associated focal
      infections indicated by increase use of acute in-hospital resource utilization.
      The apparent increase in in-hospital morbidity related to these conditions should
      be considered in future evaluations of vaccine efficacy, novel therapeutics, and
      hospital resource allocation.

PMID- 20803663
TI  - In response to: Safety and efficacy of continuous insulin infusion in noncritical
      care settings.

PMID- 20803664
TI  - Comment on: Staphylococcus aureus bacteremia (SAB) with associated S. aureus
      bacteriuria (SABU) as a predictor of complications and mortality.

PMID- 20803665
TI  - Research is needed into the role of preoperative HbA1c screening in cost control.

PMID- 20803666
TI  - In response to: The paradox of readmission.

PMID- 20803667
TI  - Hospitalists: lean leaders for hospitals.

PMID- 20803668
TI  - Author responsibilities and disclosures at the journal of hospital medicine.

PMID- 20803669
TI  - Where did the day go?--a time-motion study of hospitalists.
AB  - BACKGROUND: Within the last decade hospitalists have become an integral part of
      inpatient care in the United States and now care for about half of all Medicare
      patients requiring hospitalization. However, little data exists describing
      hospitalist workflow and their activities in daily patient care. OBJECTIVE: To
      clarify how hospitalists spend their time and how patient volumes affect their
      workflow. DESIGN: Observers continuously shadowed each of 24 hospitalists for two
      complete shifts. Observations were recorded using a handheld computer device with
      customized data collection software. SETTING: Urban, tertiary care, academic
      medical center. RESULTS: : Hospitalists spent 17% of their time on direct patient
      contact, and 64% on indirect patient care. For 16% of all time recorded, more
      than one activity was occurring simultaneously (i.e., multitasking). Professional
      development, personal time, and travel each accounted for about 6% of their time.
      Communication and electronic medical record (EMR) use, two components of indirect
      care, occupied 25% and 34% of recorded time respectively. Hospitalists with above
      average patient loads spent less time per patient communicating with others and
      working with the EMR than those hospitalists with below average patient loads,
      but reported delaying documentation until later in the evening or next day.
      Patient load did not change the amount of time hospitalists spent with each
      patient. CONCLUSIONS: Hospitalists spend more time reviewing the EMR and
      documenting in it, than directly with the patient. Multi-tasking occurred
      frequently and occupied a significant portion of each shift.

PMID- 20803670
TI  - Hospitalist time usage and cyclicality: opportunities to improve efficiency.
AB  - BACKGROUND: Academic medical centers (AMCs) have a constrained resident work
      force. Many AMCs have increased the use of nonresident service hospitalists to
      manage continued growth in clinical volume. To optimize their time in the
      hospital, it is important to understand hospitalists' work flow. DESIGN: We
      performed a time-motion study of hospitalists carrying the admission pager
      throughout the 3 types of shifts we have at our hospital (day shift, swing shift,
      and night shift). SETTING: Tertiary academic medical center in the Midwest.
      RESULTS: Hospitalists spend about 15% of their time on direct patient care, and
      two-thirds of their time on indirect patient care. Of the indirect activities,
      communication and documentation dominate. Travel demands make up over 7% of a
      hospitalists' time. There are spikes in indirect patient care, followed closely
      by spikes in direct patient care, at shift changes. CONCLUSIONS: At our AMC,
      indirect patient care activities accounted for the majority of the admitting
      hospitalists' time spent in the hospital, with documentation and communication
      dominating this time. Travel takes a significant fraction of hospitalists' time.
      There is also a cyclical nature to activities performed throughout the day, which
      can cause patient delays and impose variability on support services. There is a
      need for both service-specific and systemic improvements for AMCs to efficiently
      manage further growth in their inpatient volume.

PMID- 20803671
TI  - The impact of fragmentation of hospitalist care on length of stay.
AB  - BACKGROUND: Different hospitalist staffing models provide different levels of
      inpatient continuity of care, which may impact length of stay (LOS). OBJECTIVE:
      To determine if fragmentation of care (FOC) by hospitalist physicians is
      associated with LOS. DESIGN: Concurrent control study. SETTING: Hospitalist
      practices managed by IPC The Hospitalist Company. PATIENTS: A total of 10,977
      patients admitted for diagnosis-related group (DRG) of 89 pneumonia with
      complications or comorbidities (PNA) or a DRG of 127 heart failure and shock (HF)
      between December 2006 and November 2007. MEASUREMENTS: FOC was defined as the
      percentage of care given by hospitalists other than the hospitalist who saw the
      patient the majority of the stay. Negative binomial regression was performed on
      DRG 89 and DRG 127 patients with LOS as the dependent variable. We adjusted for
      gender, age, severity of illness (SOI) scores, risk of mortality (ROM) scores,
      and number of secondary diagnoses, and admission day of the week. RESULTS: A 10%
      increase in fragmentation was associated with an increase of 0.39 days (P <
      0.0001) in the LOS for pneumonia, and an increase of 0.30 days (P < 0.0001) in
      LOS for heart failure. CONCLUSIONS: As FOC increased for pneumonia and heart
      failure, the LOS increased significantly. Methods to reduce fragmentation should
      be explored, while more research is needed to identify the source of the
      relationship between FOC and LOS.

PMID- 20803672
TI  - Pediatric hospital medicine core competencies: development and methodology.
AB  - BACKGROUND: Pediatric hospital medicine is the most rapidly growing site-based
      pediatric specialty. There are over 2500 unique members in the three core
      societies in which pediatric hospitalists are members: the American Academy of
      Pediatrics (AAP), the Academic Pediatric Association (APA) and the Society of
      Hospital Medicine (SHM). Pediatric hospitalists are fulfilling both clinical and
      system improvement roles within varied hospital systems. Defined expectations and
      competencies for pediatric hospitalists are needed. METHODS: In 2005, SHM's
      Pediatric Core Curriculum Task Force initiated the project and formed the
      editorial board. Over the subsequent four years, multiple pediatric hospitalists
      belonging to the AAP, APA, or SHM contributed to the content of and guided the
      development of the project. Editors and collaborators created a framework for
      identifying appropriate competency content areas. Content experts from both
      within and outside of pediatric hospital medicine participated as contributors. A
      number of selected national organizations and societies provided valuable
      feedback on chapters. The final product was validated by formal review from the
      AAP, APA, and SHM. RESULTS: The Pediatric Hospital Medicine Core Competencies
      were created. They include 54 chapters divided into four sections: Common
      Clinical Diagnoses and Conditions, Core Skills, Specialized Clinical Services,
      and Healthcare Systems: Supporting and Advancing Child Health. Each chapter can
      be used independently of the others. Chapters follow the knowledge, skills, and
      attitudes educational curriculum format, and have an additional section on
      systems organization and improvement to reflect the pediatric hospitalist's
      responsibility to advance systems of care. CONCLUSION: These competencies provide
      a foundation for the creation of pediatric hospital medicine curricula and serve
      to standardize and improve inpatient training practices.

PMID- 20803673
TI  - Effectiveness of a course designed to teach handoffs to medical students.
AB  - INTRODUCTION: Handoffs of patient care are increasingly common and are known to
      contribute to medical errors. A significant number, if not the large majority, of
      first-year Internal Medicine residents have not received formal education
      pertaining to handoffs during medical school. AIM: To develop a program designed
      to teach handoffs to medical students entering their fourth year of training.
      SETTING: University of Colorado Denver School of Medicine. PROGRAM DESCRIPTION:
      Our Handoff Selective was first offered in April 2007 as part of a 2-week
      Integrated Clinician's Course conducted once yearly between the third and fourth
      years of medical school. The Selective consisted of a didactic session in which
      communication theory and elements were discussed and a practicum in which
      students used faculty-developed case scenarios to practice both giving and
      receiving handoffs. PROGRAM EVALUATION: Sixty (the maximum number of spots
      available) out of 150 students participated in the course, although many more
      students chose the course than spots available. Prior to taking the Selective,
      medical students' confidence in performing handoffs was poor, but it improved
      after the course (P < 0.001); 92% of students felt the Handoff Selective was
      "useful" or "extremely useful." While both components of the course were thought
      to be useful to the large majority of students, the practicum portion was thought
      to be more useful (P < 0.001). DISCUSSION: Formal education on handoffs is well
      received by medical students and improves their self-perceived understanding and
      performance of handoffs.

PMID- 20803674
TI  - Comparing academic and community-based hospitalists.
AB  - In 2006, hospitalist programs were formally introduced at both an academic and
      community hospital in the same city providing an opportunity to study the
      similarities and differences in workflows in these two settings. The data were
      collected using a time-flow methodology allowing the two workflows to be compared
      quantitatively. The results showed that the hospitalists in the two settings
      devoted similar proportions of their workday to the task categories studied. Most
      of the time was spent providing indirect patient care followed by direct patient
      care, travel, personal, and other. However, after adjusting for patient volumes,
      the data revealed that academic hospitalists spent significantly more time per
      patient providing indirect patient care (Academic: 54.7 +/- 11.1 min/patient,
      Community: 41.9 +/- 9.8 min/patient, p < 0.001). Additionally, we found that
      nearly half of the hospitalists' time at both settings was spent multitasking.
      Although we found subtle workflow differences between the academic and community
      programs, their similarities were more striking as well as greater than their
      differences. We attribute these small differences to the higher case mix index at
      the academic program as well greater complexity and additional communication hand
      offs inherent to a tertiary academic medical center. It appears that
      hospitalists, irrespective of their work environment, spend far more time
      documenting, communicating and coordinating care than they do at the bedside
      raising the question, is this is a necessary feature of the hospitalist care
      model or should hospitalists restructure their workflow to improve outcomes?

PMID- 20803675
TI  - Systematic review of time studies evaluating physicians in the hospital setting.
AB  - BACKGROUND: Time studies, first developed in the late 19th century, are now being
      used to evaluate and improve worker efficiency in the hospital setting. This is
      the first review of hospital time study literature of which we are aware.
      PURPOSE: We performed a systematic review of the literature to better understand
      the available time study literature describing the activities of hospital
      physicians. DATA SOURCES: We searched MEDLINE, EMBASE, EMBASE Classic, PsycINFO,
      Cochrane Library, CINAHL, and Web of Science. We also manually reviewed the
      reference lists of retrieved articles and consulted experts in the field to
      identify additional articles for review. STUDY SELECTION: We selected studies
      that used time-motion or work-sampling performed via direct observation, included
      physicians, medical residents, or interns in their study population, and were
      performed on an inpatient hospital ward. DATA EXTRACTION: We abstracted data on
      subject population, study site, collection tools, and percentage of time spent on
      key categories of activity. DATA SYNTHESIS: Our search produced 11 time-motion
      and 2 work-sampling studies that met our criteria. These studies focused
      primarily on academic hospitals (92%) and the activities of physicians in
      training (69%). Other results varied widely. A lack of methodological
      standardization and dissimilar activity categorizations inhibited our efforts to
      summarize detailed findings across studies. However, we consistently found that
      activities indirectly related to a patient's care took more of hospital
      physicians' time than direct interaction with hospitalized patients. CONCLUSIONS:
      Time studies, when properly performed, have a great deal to offer in helping us
      understand and reengineer hospital care.

PMID- 20803676
TI  - A model of a hospitalist role in the care of admitted patients in the emergency
      department.

PMID- 20803678
TI  - Unscripted.

PMID- 20803679
TI  - The renal failure that vanished.

PMID- 20803680
TI  - A fall to remember.

PMID- 20803681
TI  - Rate of hydration in acute pancreatitis.

PMID- 20803682
TI  - Nanoscale surfacing for regenerative medicine.
AB  - Cells in most tissues reside in microenvironment surrounded with specific three
      dimensional features. The extracellular matrix or substratum with which cells
      interact often includes topography at the nanoscale. For example, the basement
      membrane of many tissues displays features of pores, fibers and ridges in the
      nanometer range. The nanoscale topography has significant effects on cellular
      behavior. Knowledge of the cell-substratum interactions is crucial to the
      understanding of many fundamental biological questions and to regenerative
      medicine. Rapid advances in nanotechnology enable cellular study on engineered
      nanoscale surfaces. Recent findings underscore the phenomenon that mammalian
      cells do respond to nanosized features on a synthetic surface. This review covers
      the commonly used techniques of engineering nanoscale surface and the techniques
      which have not been adapted but are of great potential in regenerative medicine,
      surveys the applications of nanoscale surface in regenerative medicine including
      vascular, bone, neural and stem cell tissue engineering, and discusses the
      possible mechanisms of cellular responses to nanoscale surface. A better
      understanding of the interactions between cells and nanoscale surfacing will help
      advance the field of regenerative medicine.

PMID- 20803683
TI  - Nanotubes in biosensing.
AB  - Carbon nanotubes (CNTs) have extensively been used for electrochemical and
      optical biosensing due to the unique mechanical, chemical, and electrical
      properties. This review introduces two functionalization categories, noncovalent
      interaction along the CNTs sidewalls via physical adsorption or entrapment and
      covalent binding via carboxylate chemistry or nonselective attack of nanotube
      sidewalls by highly reactive species and gives an overview on the functionalized
      CNTs-based biosensing methodologies for DNA, antigen-antibody, cells, and other
      biological molecules. Furthermore, the in vivo near-IR fluorescence biosensing
      application of CNTs with high photostability and efficiency is discussed.
      Finally, field-effect transistors based on semiconductor CNTs are also summarized
      for ultrasensitive detection. Biosensors based on CNTs provide a significant
      avenue for the detection of biomolecules in vivo and in vitro applications.

PMID- 20803687
TI  - Perspectives on R.E. Shenefelt's 1972 Teratology publication entitled
      "Morphogenesis of malformations in hamsters caused by retinoic acid: relation to
      dose and stage at treatment".

PMID- 20803688
TI  - Hyperthermia: malformations to chaperones.
AB  - Hyperthermia has been known to induce malformations in numerous animal models as
      well being associated with human abnormalities. This was apparent particularly
      when the hyperthermia exposure was during the early stages of neural development.
      Although it was recognized relatively early that these exposures induced cell
      death, the specific molecular mechanism of how a brief heat exposure was
      translated in to specific cellular functions remains largely unknown. While our
      understanding of the events that govern how cells react to heat, or stresses in
      general, has increased, there is much that remains undiscovered. In this brief
      review, animal and clinical observations are outlined as are some of the
      scientific explorations that were undertaken to characterize, define, and better
      understand the morphological, biochemical, and molecular effects of hyperthermia
      on the developing embryo.

PMID- 20803689
TI  - Cyclophosphamide and the Teratology Society: an awkward marriage.
AB  - Cyclophosphamide (CPA) is a potent and highly effective chemotherapeutic and
      immunosuppressive agent that has been marketed for about 50 years. Reports of its
      teratogenicity emerged just after the Teratology Society was established, and
      from that time forth CPA has been inextricably linked to the Society's goal of
      understanding and preventing birth defects. CPA teratogenesis was previously
      reviewed (Mirkes, 1985), and since that time the pathways leading to
      teratogenesis have become more complicated, with many contradictions. By causing
      DNA strand breaks, crosslinks, and adducts, CPA is highly effective at disrupting
      the integrity of the genome. This was the focus of CPA teratogenesis research for
      many years. However, it is now clear that CPA disrupts the embryonic epigenome
      and the functionality of the proteome, and that these perturbations are related
      to teratogenesis. CPA also induces cell-cycle arrest and apoptosis in the embryo
      but there is conflicting data as to whether these changes are embryoprotective or
      teratogenic. In addition, CPA has made a number of diverse contributions to the
      field of developmental toxicology. For example, the concept of male-mediated
      teratogenesis, in the absence of compromised fertility parameters, was
      established using CPA. Antivivisectionist sentiment has produced a resurgent
      interest in in vitro developmental toxicity screens, and with it the need to
      identify proteratogens that typically are false negatives in such systems due to
      the relative dearth of P-450 activity in early embryonic tissues. The requirement
      of P-450 for CPA-mediated embryotoxicity has made CPA an excellent tool with
      which to probe the metabolic competence of adjunct P-450 supplements in these in
      vitro systems. Recently, it was noted that in utero exposure to CPA disrupts the
      immunofunction markers at parturition, suggesting CPA may be a future model for
      developmental immunotoxicology.

PMID- 20803690
TI  - Whole embryo culture: a "New" technique that enabled decades of mechanistic
      discoveries.
AB  - Denis New's development of the rodent whole embryo culture (WEC) method in the
      early 1960s was a groundbreaking achievement that gave embryologists and
      teratologists an unprecedented degree of access to the developing
      postimplantation rodent embryo. In the five decades since its development, WEC
      has enabled detailed investigations into the regulation of normal embryo
      development as well as a plethora of research on mechanisms of teratogenesis as
      induced by a wide range of agents. In addition, WEC is one of the few techniques
      that has been validated for use in teratogenicity screening of drugs and
      chemicals. In this review, we retrace the steps leading to New's development of
      WEC, and highlight many examples in which WEC played a crucial role leading to
      important discoveries in teratological research. The impact of WEC on the field
      of teratology has been enormous, and it is anticipated that WEC will remain a
      preferred tool for teratologists and embryologists seeking to interrogate embryo
      development for many years to come.

PMID- 20803691
TI  - Zinc and reproduction: effects of zinc deficiency on prenatal and early postnatal
      development.
AB  - A large body of evidence supports the concept that human pregnancy outcome is
      significantly influenced by the nutritional status of the mother. The consumption
      of "poor diets" has been associated with an increased risk for pregnancy
      complications, including gross structural birth defects, prematurity, low birth
      weight, and an increased risk for neurobehavioral and immunological abnormalities
      after birth. Forty-four years ago, zinc deficiency in mammals was shown to be
      teratogenic. Maternal zinc deficiency produces effects ranging from infertility
      and embryo/fetal death, to intrauterine growth retardation and teratogenesis.
      Postnatal complications of maternal zinc deficiency can also occur, and include
      behavioral abnormalities, impaired immunocompetence, and an elevated risk for
      high blood pressure in the offspring. It has been suggested that developmental
      zinc deficiency in humans can present a significant challenge to the conceptus,
      increasing the risk for numerous defects. Developmental zinc deficiency can occur
      through multiple pathways, and the concept that acute phase response-induced
      changes in maternal zinc metabolism may be a common cause of embryonic and fetal
      zinc deficiency is presented. Potential mechanisms underlying the teratogenic
      effects of zinc deficiency are reviewed. The potential value of maternal zinc
      supplementation in high risk pregnancies is discussed.

PMID- 20803692
TI  - Maternal-placental insulin-like growth factor (IGF) signaling and its importance
      to normal embryo-fetal development.
AB  - As background for an antibody-based therapeutic program against the IGF receptor,
      we undertook a review of available information on the early pregnancy-specific
      regulation and localization of IGFs, IGF-binding proteins (BPs), IGFBP-specific
      proteases, and the type 1 IGF receptor relative to placental maintenance,
      function of placental nutrient transporters, placental cellular
      differentiation/turnover/apoptosis, and critical hormone signaling needed to
      maintain pregnancy. Possible adverse outcomes of altered IGF signaling include
      prenatal loss, fetal growth retardation, and maldevelopment are also discussed.
      It appears that the IGF axes in both the conceptus and mother are important for
      normal embryo-fetal growth. Thus, all molecules (i.e., both small and large) that
      disrupt the IGF axis could be expected to have some degree of fetal consequences.

PMID- 20803693
TI  - Microscopy for nanotherapeutics.

PMID- 20803694
TI  - Dynamics of nucleic acid/cationic polymer complexation and disassembly under
      biologically simulated conditions using in situ atomic force microscopy.
AB  - Elucidating dynamic morphological changes of gene-carrying vectors and their
      nucleic acid release under varying intracellular conditions has been a technical
      challenge. Atomic force microscopy (AFM) was used to observe nucleic acid/polymer
      polyplexes under endosomal and reducible cytosolic conditions. Both ketalized
      (acid-degradable) and unmodified (nondegradable) polyethylenimine (PEI) in linear
      and branched forms were used to prepare plasmid DNA- or siRNA-complexing
      polyplexes. Then, the polyplexes' complexation and disassembly were observed by
      in situ AFM in various differentially changing buffers that represent
      intracellular conditions. Results demonstrated obvious morphological destruction
      of DNA/ketalized linear PEI (KL-PEI) polyplexes under mildly acidic endosomal
      conditions, whereas no morphological changes were observed by DNA/ketalized
      branched PEI (KB-PEI) under the same conditions. In addition, siRNA was more
      efficiently dissociated from KL-PEI than KB-PEI under the same conditions.
      Nondegradable PEI did not show any evidence that DNA or siRNA was released.
      Anionic biomacromolecules (e.g., heparan sulfate), which was hypothesized to
      dissociate nucleic acids from cationic polymers, did not successfully disassemble
      polyplexes but appeared to be adsorbed on cationic polymers. The in situ AFM
      results combined with in vitro cellular transfection and gene silencing indicated
      that efficient endosomal escape of plasmid DNA in a compact polyplex form is
      required for efficient gene expression. On the contrary, rapid dissociation of
      siRNA from its cationic carrier is crucial for efficient gene silencing. The
      findings of this study may provide new insightful information for designing
      stimuli-responsive nonviral gene vectors as well as expanding tools for
      investigating nonviral vectors in nanoscales under biologically inspired
      conditions.

PMID- 20803695
TI  - Confocal microscopy for the analysis of siRNA delivery by polymeric
      nanoparticles.
AB  - Clinical applications of genetic therapies, including delivery of short,
      interfering RNAs (siRNAs) for RNA interference (RNAi), are limited due to the
      difficulty of delivering nucleic acids to specific cells of interest while at the
      same time minimizing toxicity and immunogenicity. The use of cationic polymers to
      deliver nucleic acid therapeutics has the potential to address these complex
      issues but is currently limited by low-delivery efficiencies. Although cell
      culture studies have shown that some polymers can be used to deliver siRNAs and
      achieve silencing, it is still not clear what physical or chemical properties are
      needed to ensure that the polymers form active polymer-siRNA complexes. In this
      study, we used multicolor fluorescence confocal microscopy to analyze the
      cellular uptake of siRNAs delivered by novel propargyl glycolide polymeric
      nanoparticles (NPs). Delivery by these vehicles was compared with delivery by
      linear polyethyleneimine (LPEI) and Lipofectamine 2000 (LF2K), which are both
      known as effective delivery vehicles for siRNAs. Our results showed that when
      LF2K and LPEI were used, large quantities of siRNA were delivered rapidly,
      presumably overwhelming the basal levels of mRNA to initiate silencing. In
      contrast, our novel polymeric NPs showed delivery of siRNAs but at concentrations
      that were initially too low to achieve silencing. Nonetheless, the exceptionally
      low cytotoxicity of our NPs, and the simplicity with which they can be modified,
      makes them good candidates for further study to optimize their delivery profiles
      and, in turn, achieve efficient silencing.

PMID- 20803696
TI  - Rho-kinase/ROCK: A key regulator of the cytoskeleton and cell polarity.
AB  - Rho-associated kinase (Rho-kinase/ROCK/ROK) is an effector of the small GTPase
      Rho and belongs to the AGC family of kinases. Rho-kinase has pleiotropic
      functions including the regulation of cellular contraction, motility, morphology,
      polarity, cell division, and gene expression. Pharmacological analyses have
      revealed that Rho-kinase is involved in a wide range of diseases such as
      vasospasm, pulmonary hypertension, nerve injury, and glaucoma, and is therefore
      considered to be a potential therapeutic target. This review focuses on the
      structure, function, and modes of activation and action of Rho-kinase.

PMID- 20803697
TI  - Prostaglandin E2 inhibits migration of colonic lamina propria fibroblasts.
AB  - BACKGROUND: Migration of colonic lamina propria fibroblasts (CLPF) is an
      important mechanism during wound healing in inflammatory bowel disease (IBD). The
      concentration of prostaglandin E2 (PGE2) is increased in the intestinal mucosa of
      IBD patients. We therefore investigated the role of PGE2 in CLPF migration.
      METHODS: Primary cultures of CLPF were isolated from healthy controls and Crohn's
      disease patients. Migration assays were performed in the Boyden chamber and
      scratch assays. EP receptors, PGE2, intracellular cyclic adenosine monophosphate
      (cAMP), expression and distribution of F-actin, alpha-smooth muscle actin (SMA),
      and myosin light chain (MLC) were determined by immunoblotting,
      immunocytochemistry, and enzyme-linked immunosorbent assay (ELISA). RESULTS: All
      four EP receptor subtypes were present on CLPF. PGE2 and agonists to the EP2 and
      EP4 receptor reduced the migration of CLPF. Blockade of the EP2 and the EP4
      receptor inhibited the effect of PGE2 on CLPF migration. An increase in
      intracellular cAMP reduced CLPF migration. PGE2 increased the concentrations of
      cAMP in CLPF, with abrogation after addition of EP2 and EP4 receptor antagonists.
      PGE2 and forskolin decreased the expression of alpha-SMA and F-actin and reduced
      cell polarization and lamellipodium formation in a scratch assay. In addition,
      forskolin reduced the phosphorylation of MLC (pMLC) and led to lack of
      accumulation of pMLC in the leading edge of CLPF. CONCLUSIONS: PGE2 reduced the
      migration of CLPF via elevation of intracellular cAMP. Potential mechanisms are
      changes in expression of cytoskeletal proteins, failure of CLPF to polarize, and
      a decreased amount of pMLC. This might be a possible reason for the impairment of
      intestinal wound healing in IBD.

PMID- 20803698
TI  - High incidence of inflammatory bowel disease in Australia: a prospective
      population-based Australian incidence study.
AB  - BACKGROUND: To date, there have been no population-based epidemiological studies
      published from Australia concerning the incidence of inflammatory bowel disease
      (IBD). Our hypothesis was that the incidence of IBD in Australia is at least as
      high as other industrialized countries, given similar genetic and environmental
      risk factors. METHODS: A prospective, population-based IBD incidence study was
      conducted between April 2007 and March 2008 in Greater Geelong, Victoria,
      Australia. According to 2006 Australian Census data, this comprises an at-risk
      population of 259,015. Cases were ascertained from multiple overlapping sources.
      All local general practitioners, gastroenterologists, surgeons, and pediatricians
      were contacted every 2 months to identify new IBD cases. The Royal Children's
      Hospital in Melbourne, local endoscopy and pathology centers were also searched
      to ensure completeness of case capture. Standard IBD case definitions were used
      with clinical, endoscopic, and histological criteria. RESULTS: In all, 76 new
      cases of IBD were identified during the 1-year period. There were 45 cases of
      Crohn's disease, 29 of ulcerative colitis, and 2 of indeterminate colitis. The
      crude annual incidence rates for IBD overall, Crohn's disease, ulcerative
      colitis, and indeterminate colitis were 29.3 per 100,000 (95% confidence interval
      [CI] 23.5-36.7 per 100,000), 17.4 per 100,000, 11.2 per 100,000, and 0.8 per
      100,000, respectively. When directly age-standardized to the World Health
      Organization standard population the overall IBD incidence rate was 29.6 per
      100,000. CONCLUSIONS: This is the first prospective, Australian population-based
      IBD incidence study. The incidence rates are among the highest reported in the
      literature of IBD.

PMID- 20803700
TI  - Mucosal healing as an index of colitis activity: back to histological healing for
      future indices.

PMID- 20803702
TI  - The mercaptomethyl group facilitates an efficient one-pot ligation at Xaa-Ser/Thr
      for (glyco)peptide synthesis.

PMID- 20803703
TI  - Encapsulation of DNA-templated chromophore assemblies within virus protein
      nanotubes.

PMID- 20803705
TI  - Stress-induced multiple organ damage in rats is ameliorated by the antioxidant
      and anxiolytic effects of regular exercise.
AB  - Our aim was to investigate the effects of moderate load, regular swimming
      exercise on stress-induced anxiety, and associated oxidative organ injury. Male
      Sprague-Dawley rats (n = 48) were either kept sedentary or submitted to swimming
      exercise for 8 weeks. Rats were then divided as non-stressed, acute stress, and
      chronic stress groups. After acute or chronic stress (electric foot shocks)
      applications, rats were placed on a holeboard and the exploratory behavior was
      recorded to assess the anxiety. Rats were decapitated after the stress
      application. Acute and chronic stress induction led to increased serum cortisol
      levels as compared to non-stressed groups. Plasma aspartate aminotransferase
      levels that were elevated in sedentary rats with both stress exposures were lower
      in trained rats. Malondialdehyde levels and myeloperoxidase activity were
      increased in the cardiac muscle, liver, stomach, and brain of the stressed rats
      with a concomitant reduction in the glutathione levels, while stress-induced
      changes in malondialdehyde, myeloperoxidase, and glutathione levels were reversed
      in the trained animals. Exercise, which led to increased malondialdehyde and
      reduced glutathione levels in the skeletal muscle of the non-stressed rats, also
      protected against stress-induced oxidative damage. Regular exercise with its
      anxiolytic and antioxidant effects ameliorates stress-induced oxidative organ
      damage by a neutrophil-dependent mechanism.

PMID- 20803707
TI  - Concurrently using rosiglitazone prevents glucosamine-induced islet beta-cell
      apoptosis and dysfunction.
AB  - Diabetes has merged as a significant health problem. This study aims to examine
      the effect of concurrently using rosiglitazone (RSG) on inhibiting glucosamine
      (GlcN)-induced islet beta cell apoptosis and dysfunction. Using an islet beta
      cell line, HIT-T15 cells, as a study platform, the inhibitory effect of RSG on
      GlcN-induced pathophysiological changes in islet beta cells was examined. The
      results showed that treatment with GlcN induced HIT-T15 cell death via apoptotic
      pathway, inhibited the expression of Bcl-2 and Bcl-xL, enhanced the expression of
      Bax, Bid and caspase-3, reduced the production of ATP and decreased in insulin
      secretion. The changes were in a GlcN dose-dependent manner. Concurrently using
      RSG with GlcN, the induced pathogenic changes in HIT-T15 cells were abrogated. We
      conclude that concurrently using RSG can be useful in reducing the GlcN-induced
      side effects on islet beta cells that has potential to prevent the complications
      caused by GlcN in the treatment of diabetes.

PMID- 20803706
TI  - Antioxidant activity of fluoxetine: studies in mice melanoma model.
AB  - In vivo effects of the antidepressant fluoxetine on spleen antioxidant status of
      C57BL/6 mice were studied using a melanoma experimental model. After a 14-day
      treatment with fluoxetine (10 mg kg(-1) day(-1), i.p.), the endogenous
      antioxidant non-enzyme (glutathione) and enzyme (superoxide dismutase (SOD) and
      glutathione peroxidase (GPx)) defense systems in spleen of healthy animals were
      not changed; the lipid peroxidation (LP) was also unchanged. When B16F10 melanoma
      cells were introduced in C57BL/6 mice 2 h before fluoxetine treatment, a drug
      protective effect against the melanoma-induced oxidative changes (increased LP
      and decreased total glutathione (GSH)-level, as well as antioxidant enzyme
      activities) in spleen was observed. Fluoxetine dose-dependently reduced the
      amounts of free oxygen radicals (hydroxyl and superoxide anion radicals),
      generated in chemical systems. Taken together, the present results suggest that
      fluoxetine, acting as antioxidant, prevents from melanoma-induced oxidative
      changes in mice spleen.

PMID- 20803699
TI  - Toll-like receptors in inflammatory bowel diseases: a decade later.
AB  - Differential alteration of Toll-like receptor (TLR) expression in inflammatory
      bowel disease (IBD) was first described 10 years ago. Since then, studies from
      many groups have led to the current concept that TLRs represent key mediators of
      innate host defense in the intestine, involved in maintaining mucosal as well as
      commensal homeostasis. Recent findings in diverse murine models of colitis have
      helped to reveal the mechanistic importance of TLR dysfunction in IBD
      pathogenesis. It has become evident that environment, genetics, and host immunity
      form a multidimensional and highly interactive regulatory triad that controls TLR
      function in the intestinal mucosa. Imbalanced relationships within this triad may
      promote aberrant TLR signaling, critically contributing to acute and chronic
      intestinal inflammatory processes in IBD colitis and associated cancer.

PMID- 20803708
TI  - Dehydroepiandrosterone ameliorates hepatocellular damage in obstructive jaundice.
AB  - We aimed to investigate the ameliorating effect of dehydroepiandrosterone (DHEA)
      on the potential hepatocellular damage in experimental obstructive jaundice.
      Twenty-four male rabbits in the study were randomly allocated into three groups.
      In the sham group, the choledochal canal was identified and explored. In the
      obstructive jaundice and treatment groups, the choledochal canal was ligated.
      Placebo and DHEA were administered to the obstructive jaundice and treatment
      groups, respectively. Blood samples were obtained at baseline, and both blood
      samples and liver tissue samples were obtained by re-laparotomy performed on day
      8. Biochemical parameters were measured in blood samples, and liver samples were
      histopathologically evaluated. Alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), gamma glutamyl transferase (GGT), alkaline phosphatase
      (ALP) and bilirubin levels were lower in the treatment group than in obstructive
      jaundice. Mononuclear inflammation in the portal region and hepatocyte
      degeneration were milder in the treatment group compared to obstructive jaundice
      group. Fibrosis and necrosis were also recovered by the DHEA treatment.In
      conclusion, these findings suggested that DHEA may reduce the obstructive
      jaundice-induced hepatocellular damage.

PMID- 20803710
TI  - International Journal of Geriatric Psychiatry. Editorial.

PMID- 20803709
TI  - Effects of 17beta-estradiol on cardiac apoptosis in ovariectomized rats.
AB  - OBJECTIVES: Cardiac apoptosis was found in ovariectomized rats without ischemia.
      Limited information regarding the protective effects of 17beta-estradiol (E2) on
      cardiac Fas-dependent and mitochondria-dependent apoptotic pathways after post
      menopause or bilateral oophorectomy in women was available. METHODS: Forty-eight
      female Wistar rats at 6-7 months of age were divided into sham-operated group
      (Sham, n = 16) and bilateral ovariectomized group (n = 32). After 4 weeks of
      operation, rats in ovariectomized group were injected intraperitoneally with
      either saline (OVX, n = 16) or 10 microg/kg/day 17beta-estradiol (E2) for 10
      weeks (OVX-E2, n = 16). The excised hearts were measured by Hematoxylin-eosin
      staining, DAPI staining, positive TUNEL assays, and Western Blotting. RESULTS:
      17beta-estradiol (E2) decreased OVX-induced cardiac widely dispersed TUNEL
      positive apoptotic cells. 17beta-estradiol (E2) decreased OVX-induced TNF-alpha,
      Fas ligand (Fas L), Fas death receptors (Fas), Fas-associated death domain
      (FADD), activated caspase 8, and activated caspase 3 (Fas pathways). 17beta
      estradiol (E2) decreased OVX-induced proapoptotic t-Bid, Bax, Bax-to-Bcl2 ratio,
      Bax-to-BclXL ratio, activated caspase 9, and activated caspase 3 as well as
      increased anti-apoptotic Bcl2 and Bcl-XL relative to OVX (mitochondria pathway).
      CONCLUSIONS: Our findings suggest that chronic 17beta-estradiol (E2) treatment
      can prevent ovariectomy-induced cardiac Fas-dependent and mitochondria-dependent
      apoptotic pathways in rat models. The findings may provide one of possible
      mechenisms of 17beta-estradiol (E2) for potentially preventing cardiac apoptosis
      after bilateral ovariectomy or menopause.

PMID- 20803711
TI  - Dementia services in Canada.
AB  - Canadians with dementia have access to Medicare, a universal, single payer
      healthcare program. Implementation of Medicare is through the provinces and
      territories, giving variation in the level of care available. At present, there
      is no national strategy for dementia, although a recent report from the Alzheimer
      Society of Canada is expected to catalyze one. Most dementia care is provided by
      primary care practitioners, with three specialties (geriatric psychiatry,
      geriatric medicine and neurology) providing consultant expertise. Primary care
      reforms are aimed at developing a more coordinated approach to the complex needs
      of people with dementia, and have especially emphasized education of providers.
      Any national strategy is expected to underscore prevention and research, the
      latter building on Canada's strong contribution to this international
      undertaking.

PMID- 20803712
TI  - Care for dementia in Spain: the need for a nationwide strategy.

PMID- 20803713
TI  - Developments in dementia strategy.

PMID- 20803714
TI  - Dementia services in Australia.
AB  - AIM: To describe dementia services in Australia. METHOD: Limited review of
      current government policies and relevant papers. RESULTS: Australians with
      dementia, currently estimated at 220 000, are expected to number 1.13 million by
      2050. In response, Commonwealth and State Australian governments have developed
      comprehensive plans and systems including expansion of community care services
      and packages, improvement in quality of residential care and initiatives to
      address behavioural and psychological symptoms of dementia. Alzheimer's
      Australia, which continues to be a powerful advocate for improvement in services,
      has pioneered a prevention programme to delay dementia onset. CONCLUSION: Further
      developments should aim to increase awareness, reduce stigma, enhance carer
      support improve timely diagnosis and support for special population groups,
      notably those from Indigenous and non-English speaking communities and those with
      younger onset dementia and correct relative underfunding for dementia research.
      Dementia care in Australia is well developed but gaps remain.

PMID- 20803715
TI  - The national dementia strategy in Japan.

PMID- 20803716
TI  - The French National Alzheimer disease plan 2008-2012.

PMID- 20803717
TI  - Northern Ireland dementia strategy.

PMID- 20803718
TI  - Dementia strategy in China and Hong Kong.

PMID- 20803719
TI  - Scottish dementia strategy editorial.

PMID- 20803720
TI  - Developing a national dementia strategy for Ireland.

PMID- 20803721
TI  - Living well with dementia--development of the national dementia strategy for
      England.

PMID- 20803722
TI  - National dementia plan--Wales.

PMID- 20803723
TI  - Care of the elderly in United Arab Emirates.

PMID- 20803724
TI  - The Norwegian dementia plan 2015--'making most of the good days'.

PMID- 20803725
TI  - Dementia strategy Korea.

PMID- 20803726
TI  - Association of autistic spectrum disorder with season of birth and conception in
      a UK cohort.
AB  - PURPOSE: To examine the association between autistic spectrum disorder (ASD) and
      seasons of conception and birth in a UK birth cohort: Avon Longitudinal Study of
      Parents and Children (ALSPAC). METHODS: Seasons of conception and birth were
      compared in children with and without ASD with season grouped as follows: spring
      (March-May); summer (June-August); autumn (September-November) and winter
      (December-February). RESULTS: A total of 86 children with ASD were identified in
      the ALSPAC cohort giving a prevalence of ASD of 61.9 per 10,000. There was some
      evidence for an excess of children with ASD being conceived during the summer
      months with a rate per 1,000 conceptions of 9.5 in summer compared to 5.1, 4.6,
      5.7 in spring, autumn and winter, respectively. A doubling of the odds was
      suggested for summer compared to autumn (Odds ratio 2.08 [1.18, 3.70]). In
      agreement with previous research, there was a corresponding peak in spring
      births. CONCLUSION: Conception during the summer months was associated with an
      over-representation of children with ASD in this UK birth cohort. There was also
      an association between ASD and spring births. Further investigation of seasonal
      influences on the aetiology of autism is required to identify possible factors in
      the environment, and their mechanisms and timings.

PMID- 20803727
TI  - Autism spectrum disorder: unbroken mirror neurons; rare copy number variants.

PMID- 20803729
TI  - Technology's role in healthcare reform: oncology will require different
      electronicmedical records systems.

PMID- 20803730
TI  - Gene variant may help identify patients who benefit most from statins.

PMID- 20803731
TI  - Some may benefit from combined mammography and magnetic resonance imaging.

PMID- 20803732
TI  - The physiological acquisition of amoeboid motility in nematode sperm: is the tail
      the only thing the sperm lost?
AB  - Nematode spermatozoa are highly specialized amoeboid cells that must acquire
      motility through the extension of a single pseudopod. Despite morphological and
      molecular differences with flagellated spermatozoa (including a non-actin-based
      cytoskeleton), nematode sperm must also respond to cues present in the female
      reproductive tract that render them motile, thereby allowing them to locate and
      fertilize the egg. The factors that trigger pseudopod extension in vivo are
      unknown, although current models suggest the activation through proteases acting
      on the sperm surface resulting in a myriad of biochemical, physiological, and
      morphological changes. Compelling evidence shows that pseudopod extension is
      under the regulation of physiological events also observed in other eukaryotic
      cells (including flagellated sperm) that involve membrane rearrangements in
      response to extracellular cues that initiate various signal transduction
      pathways. An integrative approach to the study of nonflagellated spermatozoa will
      shed light on the identification of unique and conserved processes during
      fertilization among different taxa.

PMID- 20803733
TI  - Signaling mechanisms in the establishment of plant and fucoid algal polarity.
AB  - The establishment of polarity is a fundamental property of most cells. In tip
      growing plant and in fucoid algal cells, polarization specifies a growth pole,
      the center of localized secretion of new plasma membrane and cell wall material,
      generating a protrusion with a dome-shaped apex. Although much progress has been
      made concerning the cellular machinery required to execute tip growth, less is
      known regarding the signaling mechanisms involved in selecting the growth site
      and regulating vectorial cell division and expansion. Fucoid algal zygotes use
      extrinsic cues to orient their growth axes and are thus well-suited for studies
      of de novo selection of an axis. This process has been investigated largely by
      both pharmacological and immuno-localization studies. In tip growing plant cells,
      polarity is often predetermined, as in the formation of root hairs or moss
      protonema branches. More focus has been on genomic and genetic studies to reveal
      the molecules involved in expressing a growth axis. Here we review the common
      roles of the cytoskeleton and signal transduction pathways in the formation of a
      developmental axis in fucoid algal cells and the control of tip growth in higher
      plant cells.

PMID- 20803734
TI  - Ethanol induces mouse spermatogenic cell apoptosis in vivo through over
      expression of Fas/Fas-L, p53, and caspase-3 along with cytochrome c translocation
      and glutathione depletion.
AB  - Although it has been well established that spermatogenic cells undergo apoptosis
      when treated with ethanol, the molecular mechanisms behind it remain to be
      investigated. Adult male mice were given intra-peritoneal injection (IP) of
      ethanol at a dose of 3 g (15%, v/v) per kg body weight per day during the period
      of 14 days. Testicular androgenesis and apoptotic germ cell death, along with
      different interrelated proteins expression, were evaluated. Ethanol treatment
      induced apoptotic spermatogenic cell death with a decrease in the plasma and
      intra-testicular testosterone concentration. Western blot analysis revealed that
      repeated ethanol treatment decreased the expression of steroidogenic acute
      regulatory protein (StAR), 3 beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17
      beta-hydroxysteroid dehydrogenase (17beta-HSD); increased the expression of
      active caspase-3, p53, Fas and Fas-L; and led to up-regulation of Bax/Bcl-2 ratio
      and translocation of cytochrome c from mitochondria to cytosol in testis. It has
      also been shown in our study that repeated ethanol treatment led to up-regulation
      of caspase-3, p53, Fas, Fas-L transcripts; increase in caspase-3 and caspase-8
      activities; diminution of 3beta-HSD, 17beta-HSD, and GPx activities; decrease in
      the mitochondrial membrane potential along with ROS generation and depletion of
      glutathione pool in the testicular tissue. The present study has indicated that
      the ethanol treatment induced apoptosis in the mouse testis through the increased
      expression of Fas/Fas-L and p53, up-regulation of Bax/Bcl-2 ratio, cytosolic
      translocation of cytochrome c along with caspase-3 activation and glutathione
      depletion.

PMID- 20803736
TI  - Cell microarrays for the screening of factors that allow the enrichment of bovine
      testicular cells.
AB  - Cell microarrays can serve as high-throughput platforms for the screening of a
      diverse range of biologically active factors and biomaterials that can induce
      desired cellular responses such as attachment, proliferation, or differentiation.
      Here, we demonstrate that surface-engineered microarrays can be used for the
      screening and identification of factors that allow the enrichment and isolation
      of rare cells from tissue-derived heterogeneous cell populations. In particular,
      we have focused on the enrichment of bovine testicular cells including type A
      spermatogonia and Sertoli cells. Microarray slides were coated with a copolymer
      synthesized from poly(ethylene glycol) methacrylate and glycidyl methacrylate to
      enable both the prevention of cell attachment between printed spots and the
      covalent anchoring of various factors such as antibodies, lectins, growth
      factors, extracellular matrix proteins, and synthetic macromolecules on printed
      spots. Microarrays were incubated with mixed cell populations from freshly
      isolated bovine testicular tissue. Overall, cell attachment was evaluated using
      CellTracker staining, whereas differential attachment of testicular cells was
      determined by immunohistochemistry staining with Plzf and vimentin antibodies as
      markers for type A spermatogonia and Sertoli cells, respectively. The results
      indicate that various surface immobilized factors, but in particular Dolichos
      biflorus lectin, allowed the enrichment of Plzf positive cells. Furthermore,
      Pisum sativum lectin, concanavalin A, collagen type IV, and vitronectin were
      identified as suitable negative selection factors. To our best knowledge, this
      work is the first to demonstrate the utility of surface engineered cell-based
      microarrays for the identification of factors that allow the selective capture of
      rare cells from tissue isolated heterogeneous mixtures.

PMID- 20803735
TI  - Application of polychromatic flow cytometry to identify novel subsets of
      circulating cells with angiogenic potential.
AB  - Defining whether human circulating proangiogenic cells represent a subset of the
      hematopoietic system and express CD45 or are hematopoietic derivatives that do
      not express CD45 (and are called endothelial progenitor cells) remains
      controversial. We have previously developed a polychromatic flow cytometry (PFC)
      protocol to isolate subsets of hematopoietic cells and we now identify the
      circulating pool of CD34(+)CD45(dim) cells representing functional circulating
      hematopoietic stem and progenitor cells (CHSPCs) that can be separated on the
      basis of AC133 expression and report that the AC133(+) subset of the CHSPCs
      enhances the growth of tumor blood vessels in vivo in immunodeficient mice. In
      addition, the ratio of AC133(+) proangiogenic CHSPCs to AC133(-) nonangiogenic
      CHSPCs unambiguously correlates with the severity of the clinical state of
      patients with peripheral arterial disease. In sum, a PFC protocol validated via
      in vitro and in vivo analyses, can be used to interrogate the roles of human
      hematopoietic elements in the growth and maintenance of the vasculature.

PMID- 20803737
TI  - Determination of lymphocyte subsets reference values in healthy Iranian men by a
      single platform flow cytometric method.
AB  - Lymphocyte subsets enumeration is of paramount importance in the management of
      immunodeficiency disorders such as HIV/AIDS. For better interpretation of
      laboratory findings, reference intervals must be determined in each population.
      Because of scarcity of published studies from Iranian population, lymphocyte
      subsets were enumerated in 142 healthy Iranian men by a single platform flow
      cytometric method. Mean and 95% confidence interval for CD4+ T cells, CD8+ T
      cells, CD4/CD8 ratio, B cells, and natural killer cells were 748.8 (351-1207),
      409.0 (192-752), 1.96 (0.77-3.70), 238.6 (82-500), and 200.7 (91-393),
      respectively. We compared our results with other studies and found significant
      differences with some of them. In conclusion, we endorse determination of
      lymphocyte subsets reference interval in different populations.

PMID- 20803739
TI  - What is the appropriate extent of lateral neck dissection in the treatment of
      metastatic well-differentiated thyroid carcinoma?

PMID- 20803740
TI  - Histopathologic findings of HPV and p16 positive HNSCC.
AB  - OBJECTIVE: Human papilloma virus (HPV) and p16INKa (p16) positivity in head and
      neck squamous cell carcinomas (HNSCCs) is currently thought to be an encouraging
      prognostic indicator. However, the histopathologic changes responsible for this
      behavior are poorly understood. It is our objective to elucidate these
      histopathologic characteristics to help define the clinical utility of these
      markers. DESIGN: Retrospective cohort study. METHODS: 71 HNSCC tumors between
      July 1, 2008 and August 30, 2009 were examined for HPV, p16, and epidermal growth
      factor receptor (EGFR). Specified pathologic features were examined: perivascular
      invasion (PVI), perineural invasion (PNI), grade of squamous differentiation,
      basaloid classification. RESULTS: HPV and p16 had no direct impact on perineural
      or perivascular invasion. However, HPV and p16 were strongly predictive of poorly
      differentiated tumors, as well as basaloid squamous cell carcinoma (SCCA) (P <
      .001). Additionally, upon multivariate analysis, HPV(+) and p16(+) tumors had an
      increased risk of nodal metastasis (HPV: odds ratio [OR] = 23.9 (2.2, 265.1) p =
      .01; p16: OR = 6.5 (1.4, 31.2) p = .02; PVI: OR = 6.0 (1.6, 22.8) p < .01). The
      area under the curve (AUC) of receiver operating characteristic (ROC) curves
      demonstrated improved predictive value for lymph node metastasis above standard
      H&E histopathologic features (76.7%) for both HPV (83.2%) and p16 (81.3%)
      individually. CONCLUSIONS: HPV(+) and p16(+) are highly predictive for poorly
      differentiated tumors and basaloid SCCA. Additionally, HPV and p16 positivity
      demonstrate superior predictive value for lymph node metastasis above standard
      H&E histopathologic features. Although exact recommendations should be tempered
      by considerations of primary tumor subsite, T-stage, and depth of invasion, head
      and neck multidisciplinary teams should strongly consider aggressive lymph node
      treatment for any HPV(+) or p16(+) tumor.

PMID- 20803741
TI  - Meta-analysis for the effect of medical therapy vs. placebo on recovery of
      idiopathic sudden hearing loss.
AB  - OBJECTIVES: To estimate the effect of recovery of idiopathic sudden hearing loss
      under placebo (first aim) and under medical therapy (second aim). STUDY DESIGN:
      Systematic review and meta-analysis. METHODS: A total of 1,674 studies published
      between January 1974 and April 2009 were found following suggestions in the
      Cochrane Handbook for Systematic Reviews. After filtering by criteria of Cochrane
      Collaboration, four trials remained for continuous and two for dichotomous data.
      RESULTS: Using Review Manager, weighted mean difference as well as standardized
      mean effect of hearing recovery were calculated and pooled. The values for
      weighted mean difference of hearing gain in dB were 0.79, 95% confidence interval
      (CI) (-2.04-3.61) and for standardized mean effect 0.06, 95% CI (-0.13-0.24),
      respectively, which computationally favors active treatment, but statistically is
      not significantly different from no effect (0 dB). This was in accordance to the
      comparison of descriptive means between recovery under placebo with 14.3 dB and
      active treatment with 15.8 dB hearing gain. Treatment effect of dichotomous data
      (hearing gain vs. no hearing gain) suggested a statistically significant better
      outcome for active treatment; the odds ratio (OR) [fixed] is 2.18 (1.06-4.46).
      CONCLUSIONS: In five different statistical analysis methods used, treatment
      effect of medical therapy was slightly better than recovery under placebo in
      which spontaneous recovery could be assumed, but no significant effect was
      detected. Against the background of recovery under placebo of 14.3 dB vs. 15.8 dB
      hearing gain of active treatment as averages of all measured frequencies,
      recovery under placebo seems not to have worse outcome than recovery under
      medical therapy.

PMID- 20803742
TI  - Determination of kinetic parameters of enantiomerization of benzothiadiazines by
      DCXplorer.
AB  - Benzothiadiazines differently substituted at the sulfonamidic nitrogen atom, at
      the stereogenic carbon atom and at the anilinic nitrogen atom have been
      synthesized and fully characterized. Enantioseparation of these compounds has
      revealed rapid on-column enantiomerization. The recently developed software
      DCXplorer has been successfully applied to calculate enantiomerization kinetic
      parameters. Enantiomerization barriers of 3-phenyl substituted benzothiadiazines,
      calculated in this work, have indicated a higher enantiomerization rate
      suggesting that the aromatic substituent exerts a strong effect on the
      enantiomerization process. Methyl substitution on N(2) position led to higher
      free energy barriers of enantiomerization, suggesting negative influence of
      methyl in the N(2) position on enantiomerization kinetics. However, methylation
      on N(4) position increases the enantiomerization rates significantly. The results
      obtained have been employed to postulate an enantiomerization mechanism for
      chiral benzothiadiazine type compounds.

PMID- 20803743
TI  - Racemization of the gastrointestinal antisecretory chiral drug esomeprazole
      magnesium via the pyramidal inversion mechanism: A theoretical study.
AB  - The pyramidal inversion mechanisms of the 6-methoxy and the 5-methoxy tautomers
      of (S)-omeprazole were studied, employing ab initio and DFT methods. The
      conformational space of the model molecule (S)-2-[(3-methyl-2
      pyridinyl)methyl]sulfinyl-1H-benzimidazole was calculated, with respect to
      rotations around single bonds, at the B3LYP/6-311G(d,p) level. All of the
      resulting conformations were used as starting points for full optimizations of
      (S)-omeprazole, at B3LYP/6-31G(d), B3LYP/6-311G(d,p), B3LYP/6-311++G(d,p),
      B3LYP/6-311G(2df,2pd), MP2/6-31G(d), and MP2/6-311G(d,p) levels. Four distinct
      pathways were found for enantiomerization via the pyramidal inversion mechanism
      for each of the tautomers of (S)-omeprazole. Each transition state, in which the
      sulfur, the oxygen and the two carbon atoms connected directly to the sulfur are
      in one plane, connects two diastereomeric minima. The enantiomerization is
      completed by free rotation around the sulfur-methylene bond, and around the
      methylene-pyridine ring bond. The effective Gibbs' free energy barrier for
      racemization DeltaG(double dagger) (rac) of the two tautomers of (S)-omeprazole
      are 39.8 kcal/mol (5-methoxy tautomer) and 40.0 kcal/mol (6-methoxy tautomer),
      indicating that the enantiomers of omeprazole are stable at room temperature (in
      the gas phase). The 5-methoxy tautomer of (S)-omeprazole was found to be slightly
      more stable than the 6-methoxy tautomer, in the gas phase. The energy barrier
      (DeltaG(++)) for the(S,M) <=>(S,P) diastereomerization of (S)-omeprazole due to
      the rotation around the pyridine chiral axis was very low, 5.8 kcal/mole at
      B3LYP/6-311G(d,p).

PMID- 20803744
TI  - Online coupling of enantioselective capillary gas chromatography with proton
      nuclear magnetic resonance spectroscopy.
AB  - The hyphenation of enantioselective capillary gas chromatography and mass
      spectrometry is not always sufficient to distinguish between structural isomers,
      thus requiring peak identification by NMR spectroscopy. Here the first online
      coupling of enantioselective capillary gas chromatography with proton nuclear
      resonance spectroscopy is described for the unfunctionalized chiral alkane 2,4
      dimethylhexane resolved on octakis(6-O-methyl-2,3-di-O-pentyl)-gamma-cyclodextrin
      at 60 degrees C. NMR allows constitutional and configurational isomers
      (diastereomers and enantiomers) to be distinguished. Enantiomers display
      identical spectra at different retention times, which enable an indirect
      identification of these unfunctionalized alkanes. The presented method is still
      at an early development stage, and will require instrumental optimization in the
      future.

PMID- 20803745
TI  - Theoretical study on the asymmetric Michael addition of cyclohexanone with trans
      beta-nitrostyrene catalyzed by a pyrrolidine-type chiral ionic liquid.
AB  - The Michael addition of cyclohexanone with trans-beta-nitrostyrene catalyzed by a
      chiral ionic liquid (CIL) pyrrolidine-imidazolium bromide, which represents a
      prototype of CIL-promoted asymmetric syntheses, has been investigated by
      performing density functional theory calculations. We show the details of the
      mechanism and energetics, the influence of the acid additive on the reactivity,
      and the functional role of the CIL in the asymmetric addition. It is found that
      the reaction proceeds via two stages, i.e., the initial enamine formation, where
      the imine complex is first created and then isomerizes into the enamine
      intermediate, and the subsequent Michael addition involving a three-step
      mechanism. The calculations show that the presence of the acid additive changes
      the imine formation mechanism and lowers the reaction barrier, as well as, more
      importantly, makes the reaction become highly thermodynamically favored. It is
      also suggested that both the anion and cation of the CIL synergically facilitate
      the reaction, which act as the proton acceptor in the imine-enamine tautomerism
      and the stabilizer of the negative charge in the C-C bond formation process,
      respectively. The present theoretical study rationalizes the early experimental
      findings well and provides aid to some extent for the rational design of
      efficient CIL catalysts.

PMID- 20803746
TI  - Synthesis and application of 3-substituted (S)-BINOL as chiral ligands for the
      asymmetric ethylation of aldehydes.
AB  - A series of (S)-BINOL ligands substituted at the 3 position with some five
      membered nitrogen-containing aromatic heterocycles were effectively prepared and
      their catalytic abilities were evaluated in the asymmetric addition of
      diethylzinc to benzaldehyde in the presence of titanium tetraisopropoxide. Under
      the optimized reaction conditions, titanium complex of (S)-3-(1H-benzimidazol-1
      yl)-1,1'-bi-2-naphthol was found to be the most efficient catalyst for asymmetric
      ethylation of various aldehydes to generate the corresponding secondary alcohols
      in up to 99% yield and 91% ee.

PMID- 20803747
TI  - Recent advances in asymmetric oxidative coupling of 2-naphthol and its
      derivatives.
AB  - The enantiomeric atropoisomers of 1,1'-binaphthyl-2,2'-diol (BINOL) have become
      one of the most widely used chiral ligands and auxiliaries for asymmetric
      synthesis. This review provides an overview of enantioselective synthesis of
      optical active BINOLs by straightforward asymmetric oxidative coupling of
      identical 2-naphthol and its substituted derivatives.

PMID- 20803748
TI  - An improved method for determining enantiomeric excess by (13)C-NMR in chiral
      liquid crystal media.
AB  - By using a combination of inverse gated (1)H decoupled (13)C-NMR experiments1
      with short acquisition times and NMR Cryo-probe technology, the sample
      requirements and experimental times necessary to accurately measure enantiomeric
      excess of small chiral molecules has been reduced 16-fold. Quality (13)C-NMR
      spectra can now be obtained from a 1 to 5 mg sample in 12 minutes. The
      enantiomeric excess determination achieved from the average integration of all
      the (13)C-resonances in the spectrum is comparable to enantiomeric excess
      measured by chiral SFC. The advantage of the NMR method is that enantiomeric
      excess can rapidly be measured in situ on practical amounts of enantioselective
      reaction products without the need for chromatographic separation or chemical
      modification and with substantially less solvent waste.

PMID- 20803749
TI  - (S)-6-Bromo-BINOL-based phosphoramidite ligand with C(1) symmetry for
      enantioselective hydrogenation and allylic substitution.
AB  - (S)-6-Br-BINOL-derived phosphoramidite, a simple monodentate ligand with a
      stereogenic center at the phosphorus atom, was synthesized for the first time.
      This stereoselector generated a high level of enantioselectivity (80-95% ee) in
      the rhodium-catalyzed hydrogenation of alpha-dehydrocarboxylic acid esters and
      was also successfully employed in the asymmetric palladium-catalyzed allylic
      substitution of (E)-1,3-diphenylallyl acetate. The optical yield also showed
      significant dependence with reaction type: up to 70% ee for allylic amination, up
      to 75% ee for allylic sulfonylation, and up to 90% ee for allylic alkylation.

PMID- 20803750
TI  - Highly enantiomeric reduction of acetophenone and its derivatives by locally
      isolated Rhodotorula glutinis.
AB  - Ninety isolates of microorganisms belonging to different taxonomical groups (30
      bacteria, 20 yeast, and 40 fungi) were previously isolated from various samples.
      These isolates were screened as reducing agents for acetophenone 1a to
      phenylethanol 2a. It was found that the isolate EBK-10 was the most effective
      biocatalyst for the enantioselective bioreduction of acetophenone. This isolate
      was identified as Rhodotorula glutinis by the VITEK 2 Compact system. The various
      parameters (pH 6.5, temperature 32 degrees C, and agitation 200 rpm) of the
      bioreduction reaction was optimized, which resulted in conversions up to 100%
      with >99% enantiomeric excesses (ee) of the S-configuration. The preparative
      scale bioreduction of acetophenone 1a by R. glutinis EBK-10 gave (S)-1
      phenylethanol 2a in 79% yield, complete conversion, and >99% ee. In addition,
      R.glutinis EBK-10 successfully reduced various substituted acetophenones.

PMID- 20803751
TI  - A novel chiral aliphatic-aromatic diamine promoted direct, highly enantio- and
      diastereoselective Michael addition of cyclohexanone to nitroolefins under
      solvent-free conditions.
AB  - A series of new highly efficient chiral aliphatic-aromatic diamine catalysts have
      been designed and successfully applied to the asymmetric Michael addition of
      cyclohexanone with nitroolefins under solvent-free conditions without any acidic
      additives. The desired adducts were obtained in high yields with excellent
      enantio- and diastereoselectivities of syn products (up to >99% ee, >99:1 dr).

PMID- 20803753
TI  - Fabrication of a microfluidic Ag/AgCl reference electrode and its application for
      portable and disposable electrochemical microchips.
AB  - This report describes a convenient method for the fabrication of a miniaturized,
      reliable Ag/AgCl reference electrode with nanofluidic channels acting as a salt
      bridge that can be easily integrated into microfluidic chips. The Ag/AgCl
      reference electrode shows high stability with millivolt variations. We
      demonstrated the application of this reference electrode in a portable
      microfluidic chip that is connected to a USB-port microelectrochemical station
      and to a computer for data collection and analysis. The low fabrication cost of
      the chip with the potential for mass production makes it disposable and an
      excellent candidate for real-world analysis and measurement. We used the chip to
      quantitatively analyze the concentrations of heavy metal ions (Cd(2+) and Pb(2+))
      in sea water. We believe that the Ag/AgCl reference microelectrode and the
      portable electrochemical system will be of interest to people in microfluidics,
      environmental science, clinical diagnostics, and food research.

PMID- 20803752
TI  - Crucial role of cytochrome P450 in hepatotoxicity induced by 2,3-dimethoxy-1,4
      naphthoquinone in rats.
AB  - Quinone toxicity is induced by two principal mechanisms: arylation/alkylation and
      a redox cycle. We have previously shown that increases in intracellular levels of
      superoxide anion and cell death induced by 2,3-dimethoxy-1,4-naphthoquinone
      (DMNQ), a redox cycling quinone, are enhanced by pretreatment of rat primary
      hepatocytes with cytochrome P450 inhibitors. This indicates a novel interaction
      of quinones with cytochrome P450, and is thus worthy of further investigation
      using an in vivo model. The aim of this study was to examine the effects of
      cytochrome P450 inhibitors on DMNQ-induced hepatotoxicity in rats. When DMNQ was
      administered intraperitoneally, the activities of serum alanine aminotransferase
      and aspartate aminotransferase were found to increase in a dose-dependent manner,
      indicating that hepatotoxicity was induced by treatment with DMNQ. Pretreatment
      with the cytochrome P450 inhibitors SKF-525A (SKF), cimetidine and ketoconazole
      potentiated the DMNQ-induced hepatotoxicity. The blood concentration of DMNQ was
      not affected by administration of SKF. Pretreatment with the antioxidant alpha
      tocopherol almost completely attenuated the hepatotoxicity induced by DMNQ and by
      the combination of DMNQ with SKF. Levels of reduced glutathione in the liver were
      decreased and levels of oxidized glutathione were increased by treatment with
      DMNQ. These effects were potentiated by pretreatment with SKF. DMNQ-induced lipid
      peroxidation in the liver was also enhanced by pretreatment with SKF. Taken
      together, these results indicate that DMNQ-induced hepatotoxicity is augmented by
      inhibition of cytochrome P450 and that this augmentation is due to the
      enhancement of oxidative stress.

PMID- 20803754
TI  - Polystyrene spheres coated with gold nanoparticles for detection of DNA.
AB  - A novel method has been developed here utilizing gold-modified polystyrene
      spheres (PS@Au) as carriers for the investigation of DNA hybridization. The
      immobilization ability of DNA probes on the PS@Au was investigated by a quartz
      crystal microbalance (QCM). More gold nanoparticles (AuNPs) were conjugated to
      the QCM surface in the form of PS@Au as compared with the AuNPs alone. The
      influence of PS, AuNPs population and size on the DNA probe fixation, and
      hybridization has been investigated. The results show that more AuNPs were
      achievable onto the QCM surface and could greatly increase the immobilization
      amount further hybridization amount of DNA. There was an optimal surface
      curvature for the probe DNA absorption. The curvature about 12 nm was more suited
      to the adsorption of probe DNA which could lead to the detection limit further
      down to 10(-12) M. These results demonstrate that the introduction of PS@Au, with
      polystyrene spheres as the medium between the QCM surface and the AuNPs, could
      achieve modified QCM surfaces and increase its detection ability for a better DNA
      assay and a novel platform for the fabrication of DNA sensors.

PMID- 20803756
TI  - A novel PEG coating immobilized onto capillary through polydopamine coating for
      separation of proteins in CE.
AB  - The antifouling PEG-immobilized capillary was introduced for the protein
      separation in CE through mussel adhesive protein inspired polydopamine coating
      for the first time. The polydopamine, formed by spontaneous oxidative
      polymerization of dopamine at alkaline in the inner surface of capillary, was
      exploited to immobilize amine-functionalized PEG onto the capillary surface.
      During the process, polydopamine-graft-PEG copolymer was formed via Michael
      addition or Schiff base reactions. The polymer coating was observed using X-ray
      photoelectron spectroscopy and SEM. And both of them indicated the formation of
      the polymer coating. A comparative study of EOF showed that the novel coating
      could provide effective suppression of EOF and minimized adsorption of proteins.
      As a consequence, fast and efficient separations of three proteins such as
      lysozyme, cytochrome c, and ribonuclease A were obtained within a broad pH range.
      Furthermore, the long-term stability of polydopamine-graft-PEG coating in
      consecutive protein separation runs and the high separation efficiency proved
      that this novel coating was capable of minimizing protein adsorption during the
      capillary separation. The successful capillary performance also was demonstrated
      in the separation of protein mixture and milk powder samples at acidic pH.

PMID- 20803755
TI  - Polymeric nanopillar arrays for cell traction force measurements.
AB  - This paper reports the development of a novel force measurement device based on
      polymeric nanopillar arrays. The device was fabricated by a process combining
      nanosphere lithography, oxygen plasma treatment, deep etching and nano-molding.
      Well-ordered polymeric nanopillar arrays with various diameters and aspect ratios
      were fabricated and used as cell culture substrates. Cell traction forces were
      measured by the deflection of the nanopillars. Since the location of the
      nanopillars can be monitored at all times, this device allows for the measurement
      of the evolution of adhesion forces over time.

PMID- 20803757
TI  - Polythiophene-fullerene based photodetectors: tuning of spectral response and
      application in photoluminescence based (bio)chemical sensors.
AB  - A photoluminescence (PL)-based oxygen and glucose sensor utilizing inorganic or
      organic light emitting diode as the light source, and polythiophene: fullerene
      type bulk-heterojunction devices as photodetectors, for both intensity and decay
      time based monitoring of the sensing element's PL. The sensing element is based
      on the oxygen-sensitive dye Pt-octaethylporphyrin embedded in a polystyrene
      matrix.

PMID- 20803758
TI  - Sound-driven piezoelectric nanowire-based nanogenerators.

PMID- 20803759
TI  - Dry autoclaving for the nanofabrication of sulfides, selenides, borides,
      phosphides, nitrides, carbides, and oxides.
AB  - This review compiles various nanostructures fabricated by a distinct "dry
      autoclaving" approach, where the chemical reactions are carried out without
      solvents; above the dissociation temperature of the chemical precursor(s) at
      elevated temperature in a closed reactor. The diversity to fabricate carbides
      (SiC, Mo(2) C, WC), oxides (VOx-C, ZnO, Eu(2) O(3) , Fe(3) O(4) , MoO(2) ),
      hexaborides (LaB(6) , CeB(6) , NdB(6) , SmB(6) , EuB(6) , GdB(6) ), nitrides
      (TiN, NbN, TaN), phosphides (PtP(2) , WP), sulfides (ZnS, FeS/C, SnS/C, WS(2) ,
      WS(2) /C), and selenides (Zn(1-x) Mn(x) Se/C, Cd(1-x) Mn(x) Se/C), with various
      shapes and sizes is accounted with plausible applications. This unique single
      step, solvent-free synthetic process opens up a new route in the growing
      nanomaterials science; owing to its considerable advantages on the existing
      approaches.

PMID- 20803760
TI  - Improved SERS performance from Au nanopillar arrays by abridging the pillar tip
      spacing by Ag sputtering.
AB  - Ag-capped Au nanopillar arrays on a resin supporter (see left upper figure), with
      a typical adjacent pillar tip gap of 10 nm, show obviously higher surface
      enhanced Raman scattering (SERS) sensitivity (right column in red) than that of
      the bare Au nanopillar array while using 10 nM R6G as probe molecules. The large
      area Ag-capped Au nanopillar array has potential in trace detection of special
      chemicals.

PMID- 20803761
TI  - Dynamic modulation of photonic bandgaps in crystalline colloidal arrays under
      electric field.

PMID- 20803762
TI  - Size-dependent LCST transitions of polymer-coated gold nanoparticles: cooperative
      aggregation and surface assembly.

PMID- 20803763
TI  - Mixed self-assembled monolayer gate dielectrics for continuous threshold voltage
      control in organic transistors and circuits.

PMID- 20803764
TI  - Crystal habit-tuned nanoplate material of Li[Li1/3-2x/3NixMn2/3-x/3]O2 for high
      rate performance lithium-ion batteries.
AB  - A cathode for high-rate performance lithium-ion batteries (LIBs) has been
      developed from a crystal habit-tuned nanoplate Li(Li(0.17)Ni(0.25)Mn(0.58))O2
      material, in which the proportion of (010) nanoplates (see figure) has been
      significantly increased. The results demonstrate that the fraction of the surface
      that is electrochemically active for Li(+) transportation is a key criterion for
      evaluating the different nanostructures of potential LIB materials.

PMID- 20803765
TI  - A luminescent molecular thermometer for long-term absolute temperature
      measurements at the nanoscale.

PMID- 20803766
TI  - Silicon-based near-visible logpile photonic crystal.
AB  - A nanocavity structure is embedded inside a silicon logpile photonic crystal that
      demonstrates tunable absorption behavior at near visible wavelengths well beyond
      the absorption edge of silicon. This is due to silicon's indirect bandgap
      resulting in a relatively slow increase in the absorption of silicon with
      decreasing wavelength. Our results open up the possibility of utilizing the wide,
      complete three dimensional photonic gap enabled by the large refractive index of
      silicon to create three dimensional photonic crystal based devices well into the
      visible regime.

PMID- 20803768
TI  - Comparative features of colorectal and gastric cancers with microsatellite
      instability in Chinese patients.
AB  - OBJECTIVE: The purpose of this study was to determine the unique and universal
      features of microsatellite instability-high (MSI-H) colorectal cancer (CRC) and
      MSI-H gastric cancer (GC) in the Chinese population. METHODS: A new panel of
      mononucleotide MSI markers, BAT25, BAT26, NR21, NR24, and MONO-27, was used to
      define MSI status in 303 CRC and 288 GC subjects. Clinicopathological features of
      both types of MSI-H tumors were analyzed. Methylation analysis in the hMLH1
      promoter region by methylation specific polymerase chain reaction (PCR) and
      mutation detection of hMSH2/hMLH1 genes by denaturing high-performance liquid
      chromatography (DHPLC) were carried out simultaneously. RESULTS: MSI-H CRCs and
      MSI-H GCs account for 11.9% and 8.0% of unselected sporadic CRCs and GCs,
      respectively. MSI-H CRCs are strongly characterized by early onset, right-side
      location, low differentiation, mucinous tumor, less infiltration, less lymphatic
      metastasis, and more often familial tumor. MSI-H GCs only showed site preference
      for the antrum and less lymphatic metastasis. Genetic and epigenetic analyses
      were positive in 6/36 MSI-H CRCs and 0/23 MSI-H GCs with pathological mutation in
      major mismatch repair genes, and in 7/36 MSI-H CRCs and 18/23 MSI-H GCs with
      methylated hMLH1 promoter (P<0.01), respectively. CONCLUSIONS: Although there are
      many differences in the genetic basis and clinicopathological features between
      MSI-H CRC and MSI-H GC, when compared with their microsatellite stable (MSS)
      counterparts, site preference and lymphatic metastasis are features common to
      both types of MSI-H tumors.

PMID- 20803767
TI  - Body mass index, waist circumference, and cardiometabolic risk factors in young
      and middle-aged Chinese women.
AB  - OBJECTIVE: To assess the associations between body mass index (BMI), waist
      circumference (WC), and cardiometabolic risk factors in young and middle-aged
      Chinese women. METHODS: A total of 3011 women (1938 young women, 1073 middle-aged
      women), who visited our health care center for a related health checkup, were
      eligible for study. BMI and WC were measured. The subjects were divided into
      normal and overweight/obesity groups based on BMI, and normal and abdominal
      obesity groups based on WC. Cardiometabolic variables included triglyceride (TG),
      high density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG),
      homeostasis model assessment of insulin resistance (HOMA-IR), and blood pressure
      (BP). RESULTS: The prevalence of overweight/obesity was significantly higher in
      middle-aged women (32.4%) than in young women (12.0%). The prevalence of
      abdominal obesity was also higher in middle-aged women (60.3%) than in young
      women (36.2%). There were significant differences in the comparison of all
      related cardiometabolic variables between different BMI (or WC) categories in
      young and middle- aged women groups, respectively. After adjustment for age,
      partial correlation analysis indicated that both BMI and WC were correlated
      significantly with all related cardiometabolic variables. After adjustment for
      age and WC, although the correlation coefficient r' was attenuated, BMI was still
      correlated significantly with all related cardiometabolic variables in young and
      middle-aged women. After adjustment for age and BMI, partial correlation analysis
      showed that WC was correlated significantly with TG, FBG, HOMA-IR, and HDL-C in
      young women and significantly with TG, HOMA-IR, and HDL-C in middle-aged women.
      CONCLUSIONS: The prevalence of overweight/obesity and abdominal obesity was high
      in Chinese young and middle-aged women. BMI was a better predictor of
      cardiovascular disease and diabetes than WC in young and middle-aged women, and
      moreover, measurement of both WC and BMI may be a better predictor of
      cardiovascular disease and diabetes mellitus than BMI or WC alone.

PMID- 20803769
TI  - Cordycepin induces apoptosis by enhancing JNK and p38 kinase activity and
      increasing the protein expression of Bcl-2 pro-apoptotic molecules.
AB  - OBJECTIVE: To explore the molecular mechanism by which cordycepin inhibits cell
      proliferation and induces apoptosis of human colorectal cancer cells. METHODS:
      Cell counting and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2
      (4-sulfopheny)-2H-tetrazolium, inner salt) method were used to monitor the
      effects of cordycepin on cell proliferation. Flow cytometry (FCM) was used to
      analyze the effects of cordycepin on the cell cycle progress. Annexin V
      fluorescein isothiocyanate (FITC) analysis was used to detect apoptosis at a very
      early stage. Caspase-Glo was used to determine caspase activity and Western blot
      was used to measure protein expression levels of c-Jun N-terminal kinase (JNK),
      p38, and Bcl-2 pro-apoptosis family. RESULTS: The numbers of viable SW480 and
      SW620 cells and the proliferation of these cells were significantly reduced with
      increases in cordycepin concentration (P<0.01). The cell cycle progression of
      SW480 and SW620 was arrested at the G0/G1 phase by the addition of cordycepin,
      and apoptosis rates of cordycepin treatments were increased compared with the
      control group. Cordycepin-treated cells showed phosphatidylserine valgus,
      suggesting the existence of early apoptosis. Caspase-3/7 and -9 activity
      significantly increased and the protein expression levels of JNK, p38, and Bax,
      Bid, Bim, and Puma from Bcl-2 pro-apoptosis molecules also increased after the
      treatment with cordycepin. CONCLUSIONS: Cordycepin can inhibit SW480 and SW620
      cell proliferation and induce apoptosis. Apoptosis might be induced by enhancing
      JNK and p38 kinase activity and increasing the protein expression of Bcl-2 pro
      apoptotic molecules.

PMID- 20803770
TI  - Sevoflurane postconditioning reduces myocardial reperfusion injury in rat
      isolated hearts via activation of PI3K/Akt signaling and modulation of Bcl-2
      family proteins.
AB  - Sevoflurane postconditioning reduces myocardial infarct size. The objective of
      this study was to examine the role of the phosphatidylinositol-3-kinase
      (PI3K)/Akt pathway in anesthetic postconditioning and to determine whether
      PI3K/Akt signaling modulates the expression of pro- and antiapoptotic proteins in
      sevoflurane postconditioning. Isolated and perfused rat hearts were prepared
      first, and then randomly assigned to the following groups: Sham-operation (Sham),
      ischemia/reperfusion (Con), sevoflurane postconditioning (SPC), Sham plus 100
      nmol/L wortmannin (Sham+Wort), Con+Wort, SPC+Wort, and Con+dimethylsulphoxide
      (DMSO). Sevoflurane postconditioning was induced by administration of sevoflurane
      (2.5%, v/v) for 10 min from the onset of reperfusion. Left ventricular developed
      pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), maximum
      increase in rate of LVDP (+dP/dt), maximum decrease in rate of LVDP (-dP/dt),
      heart rate (HR), and coronary flow (CF) were measured at baseline, R30 min (30
      min of reperfusion), R60 min, R90 min, and R120 min. Creatine kinase (CK) and
      lactate dehydrogenase (LDH) were measured after 5 min and 10 min reperfusion.
      Infarct size was determined by triphenyltetrazolium chloride staining at the end
      of reperfusion. Total Akt and phosphorylated Akt (phospho-Akt), Bax, Bcl-2, Bad,
      and phospho-Bad were determined by Western blot analysis. Analysis of variance
      (ANOVA) and Student-Newman-Keuls' test were used to investigate the significance
      of differences between groups. The LVDP, + or - dP/dt, and CF were higher and
      LVEDP was lower in the SPC group than in the Con group at all points of
      reperfusion (P<0.05). The SPC group had significantly reduced CK and LDH release
      and decreased infarct size compared with the Con group [(22.9 + or - 8)% vs.
      (42.4 + or - 9.4)%, respectively; P<0.05]. The SPC group also had increased the
      expression of phospho-Akt, Bcl-2, and phospho-Bad, and decreased the expression
      of Bax. Wortmannin abolished the cardioprotection of sevoflurane
      postconditioning. Sevoflurane postconditioning may protect the isolated rat
      heart. Activation of PI3K and modulation of the expression of pro- and
      antiapoptotic proteins may play an important role in sevoflurane-induced
      myocardial protection.

PMID- 20803771
TI  - Personalized image-based templates for precise acetabular prosthesis placement in
      total hip arthroplasty: a pilot study.
AB  - OBJECTIVE: In order to achieve accurate implantation of the acetabular prosthesis
      in total hip arthroplasty (THA), we designed individual templates based on a
      three-dimensional (3D) model generated from computed tomography (CT) scans.
      METHODS: Individual templates were designed for 12 patients who underwent THA. A
      physical template was designed to conform to the contours of the patient's
      acetabulum and to confirm the rotation of the acetabular center. This guided the
      acetabular component orientation. RESULTS: The preoperative and postoperative X
      ray and CT scans were obtained to assess the location with respect to the
      accuracy of the acetabular component. For all patients, the abduction angle of
      the acetabular component was 46.7 degrees to 54.3 degrees and the anteversion
      angle was 11.3 degrees to 18.5 degrees . CONCLUSIONS: The assessment of
      postoperative CT scans demonstrated higher accuracy of the acetabular component
      bore when used with the individual template. Therefore, the individual template
      can be an alternative to the computer-assisted navigation systems, with a good
      cost-performance ratio.

PMID- 20803772
TI  - Chewing substances with or without tobacco and risk of cardiovascular disease in
      Asia: a meta-analysis.
AB  - OBJECTIVE: To assess whether people who ever use any form of chewing substance in
      Asia are at increased risk of cardiovascular disease (CVD). METHODS: PubMed and
      ISI Web of Science were searched for relevant studies, with no limitation on
      language or study year. Studies were included if they provided quantitative
      estimate of the association between ever use of chewing substance and the
      occurrence of CVD. Two authors independently implemented inclusion criteria,
      abstracted study characteristics, and performed meta-analysis. Summary relative
      risks were estimated on the basis of a random effect model. We used Q statistic
      and Egger's test to examine heterogeneity across studies and potential
      publication bias, respectively. RESULTS: Eight eligible studies were included.
      The relative risk of CVD for ever using chewing substances with or without
      tobacco was 1.26 (95% confidence interval (CI) 1.12-1.40), which was unchanged
      when restricted to cohort studies [1.25 (1.08-1.42)] or cohort studies in Taiwan
      [1.31 (1.12-1.51)]. The summary relative risk for ischemic heart disease was 1.27
      (1.02-1.52), and was lowered to 1.26 (0.85-1.67) after exclusion of a cross
      sectional study. The overall relative risk for cerebrovascular disease was 1.32
      (1.08-1.56). On the basis of the Taiwan data, the summary relative risk of CVD
      for betel (Areca catechu) chewing was 1.30 (1.17-1.44). Data on dose-response
      were limited to betel chewing in Taiwan, suggesting a relationship between risk
      of CVD and cumulative exposure. Two large cohorts in Taiwan reported a greater
      risk of CVD with betel chewing than with smoking. CONCLUSIONS: An association was
      detected between betel chewing with or without tobacco and the risk of CVD. Betel
      chewing may impose a greater CVD risk than smoking. More effort is needed in
      developing betel chewing cessation programmes. The relationship between betel
      chewing and subgroups of CVD requires further investigation.

PMID- 20803774
TI  - Developing new SSR markers from ESTs of pea (Pisum sativum L.).
AB  - The development of expressed sequence tags (ESTs) from pea has provided a useful
      source for mining novel simple sequence repeat (SSR) markers. In the present
      research, in order to find EST-derived SSR markers, 18 552 pea ESTs from the
      National Center for Biotechnology Information (NCBI) database were downloaded and
      assembled into 10 086 unigenes. A total of 586 microsatellites in 530 unigenes
      were identified, indicating that merely 5.25% of sequences contained SSRs. The
      most abundant SSRs within pea were tri-nucleotide repeat motifs, and among all
      the tri-nucleotide repeats, the motif GAA was the most abundant type. In total,
      49 SSRs were used for primer design. EST-SSR loci were subsequently screened on
      10 widely adapted varieties in China. Of these, nine loci showed polymorphic
      profiles that revealed two to three alleles per locus. The polymorphism
      information content value ranged from 0.18 to 0.58 with an average of 0.41.
      Furthermore, transferable analysis revealed that some of these loci showed
      transferability to faba bean. Because of their polymorphism and transferability,
      these nine novel EST-SSRs will be valuable tools for marker-assisted breeding and
      comparative mapping of pea in the future.

PMID- 20803773
TI  - Is short-term therapy really sufficient to eradicate Helicobacter pylori
      infection?
AB  - OBJECTIVE: The aim of our study was to perform a systematic review and meta
      analysis of the efficacy of short-term protocols for Helicobacter pylori
      eradication and to review the safety and adverse profiles of these eradication
      protocols. METHODS: Literatures were located through electronic searches by
      PubMed, Medline, ISI Web of Knowledge, and Cochrane Library using the relevant
      terms. Abstracts of important meetings were searched manually in some journal
      supplements. Additional bibliographies were identified from the reference lists
      of identified studies. Three independent reviewers systemically identified
      randomized controlled trials (RCTs) comparing short-duration protocols vs. 7-d
      proton pump inhibitor (PPI)-based triple protocols, as well as studies reporting
      eradication rates of short-duration protocols for H. pylori. Summary effect size
      was calculated as relative risk (RR) and 95% confidence intervals (CI) using
      Review Manager 4.2, and P<0.05 was defined as statistically significant in all
      analyses. RESULTS: Among 90 abstracts retrieved, 15 studies were analyzed,
      including a total of 30 treatment regimens with 1856 subjects. Mean intention-to
      treat (ITT) cure rates of 63.2% and 81.3% were achieved with short-term protocols
      and 7-d PPI-containing protocols, respectively. Per-protocol (PP)-based overall
      cure rates were 66.6% and 86.1%, respectively. Short-term therapy was inferior to
      7-d triple regimen (P<0.00001). After sub-analysis, however, comparing the
      effects of > or = 3-d protocols and 7-d triple protocols, the cumulative ITT RR
      was 0.95 (P=0.26), and PP RR was 0.95 (P=0.10), without significant
      heterogeneity. Moreover, slightly fewer adverse-effects were found in short-term
      protocols. CONCLUSIONS: Although more economical, short-duration protocols are
      inferior to 7-d PPI-based triple protocols with regarding to eradication rate of
      H. pylori. Protocols of more than 3 d, however, may be equivalent to 7-d
      protocols.

PMID- 20803775
TI  - Analysis of the 3' ends of tRNA as the cause of insertion sites of foreign DNA in
      Prochlorococcus.
AB  - The purpose of this study was to investigate the characteristics of transfer RNA
      (tRNA) responsible for the association between tRNA genes and genes of apparently
      foreign origin (genomic islands) in five high-light adapted Prochlorococcus
      strains. Both bidirectional best BLASTP (basic local alignment search tool for
      proteins) search and the conservation of gene order against each other were
      utilized to identify genomic islands, and 7 genomic islands were found to be
      immediately adjacent to tRNAs in Prochlorococcus marinus AS9601, 11 in P. marinus
      MIT9515, 8 in P. marinus MED4, 6 in P. marinus MIT9301, and 6 in P. marinus
      MIT9312. Monte Carlo simulation showed that tRNA genes are hotspots for the
      integration of genomic islands in Prochlorococcus strains. The tRNA genes
      associated with genomic islands showed the following characteristics: (1) the
      association was biased towards a specific subset of all iso-accepting tRNA genes;
      (2) the codon usages of genes within genomic islands appear to be unrelated to
      the codons recognized by associated tRNAs; and, (3) the majority of the 3' ends
      of associated tRNAs lack CCA ends. These findings contradict previous hypotheses
      concerning the molecular basis for the frequent use of tRNA as the insertion site
      for foreign genetic materials. The analysis of a genomic island associated with a
      tRNA-Asn gene in P. marinus MIT9301 suggests that foreign genetic material is
      inserted into the host genomes by means of site-specific recombination, with the
      3' end of the tRNA as the target, and during the process, a direct repeat of the
      3' end sequence of a boundary tRNA (namely, a scar from the process of insertion)
      is formed elsewhere in the genomic island. Through the analysis of the sequences
      of these targets, it can be concluded that a region characterized by both high GC
      content and a palindromic structure is the preferred insertion site.

PMID- 20803776
TI  - Effect of interrupted endogenous BMP/Smad signaling on growth and steroidogenesis
      of porcine granulosa cells.
AB  - Bone morphogenetic proteins (BMPs) play a critical role in the growth and
      steroidogenesis of granulosa cells (GCs). BMP signals act through membrane-bound
      heteromeric serine/threonine kinase receptors. Upon ligand binding, BMPs activate
      intracellular Smad proteins and regulate growth and apoptosis in various cell
      types. The objective of this study was to demonstrate the effects of BMP/Smad
      signal on growth and steroidogenesis of porcine GCs. A strategy of RNA
      interference (RNAi)-mediated 'gene silencing' of Smad4, a core molecule mediating
      the intracellular BMP/Smad signal transduction pathways, was used to interrupt
      endogenous BMP/Smad signaling. Results indicate that Smad4-small interfering RNA
      (siRNA) caused specific inhibition of Smad4 mRNA and protein expression after
      transfection. Interrupted endogenous BMP/Smad signaling significantly inhibited
      growth, and induced apoptosis of porcine GCs, while decreasing estradiol
      production. In addition, interrupted BMP/Smad signaling significantly (P<0.05)
      changed the expression of Cyclin D2, CDK4, Bcl-2, and Cyp19a1. These findings
      provide new insights into how BMP/Smad signaling regulates the growth and
      steroidogenesis of porcine GCs.

PMID- 20803778
TI  - I'm in considerable pain from my knee (I'm a former jock and weekend warrior) and
      want to know what the treatment options are for knee pain.

PMID- 20803777
TI  - Using chimeric piggyBac transposase to achieve directed interplasmid
      transposition in silkworm Bombyx mori and fruit fly Drosophila cells.
AB  - The piggyBac transposon has been long used to integrate foreign DNA into insect
      genomes. However, undesirable transgene expression can result from random
      insertions into the genome. In this study, the efficiency of chimeric Gal4
      piggyBac transposase in directing integration onto a DNA target plasmid was
      evaluated in cultured silkworm Bombyx mori Bm-12 and fruit fly Drosophila
      Schneider 2 (S2) cells. The Gal4-piggyBac transposase has a Gal4 DNA-binding
      domain (DBD), and the target plasmid has upstream activating sequences (UAS) to
      which the Gal4 DBD can bind with high affinity. The results indicate that, in the
      Bm-12 and S2 cells, transpositional activity of Gal4-piggyBac transposase was
      increased by 4.0 and 7.5 times, respectively, compared to controls, where Gal4
      UAS interaction was absent. Moreover, the Gal4-piggyBac transposase had the
      ability of directing piggyBac element integration to certain sites of the target
      plasmid, although the target-directing specificity was not as high as expected.
      The chimeric piggyBac transposase has the potential for use in site-directed
      transgenesis and gene function research in B. mori.

PMID- 20803779
TI  - A friend was recently taken to the ER due to shortness of breath and chest pain,
      and was told she had coronary microvascular disease.  What is this, and how is it
      detected and treated?

PMID- 20803780
TI  - Men who have sex with men prefer rapid testing for syphilis and may test more
      frequently using it.
AB  - Most Australian men who have sex with men who underwent rapid testing for
      syphilis using the Determine Syphilis TP immunoassay indicated a preference for
      rapid testing over conventional serology. Most also indicated that they would
      test for syphilis more frequently if rapid syphilis testing was available in a
      clinic setting.

PMID- 20803783
TI  - NIH aims to increase number of minority scientists.

PMID- 20803784
TI  - Rabbits' feet and four-leaf clovers II. By Caveman.

PMID- 20803782
TI  - Prevalence and correlates of Trichomonas vaginalis infection among female US
      federal prison inmates.
AB  - BACKGROUND: Previous studies have observed high prevalences of Trichomonas
      vaginalis infection among women entering US jails and state prisons (22%-47%). We
      sought to determine the prevalence among women incarcerated in 2 US female-only
      federal prisons. METHODS: Female inmates were recruited at 2 prisons (n = 624).
      Participants completed a self-administered questionnaire and provided self
      collected first-catch urine and vaginal swab specimens. Specimens were tested for
      T. vaginalis DNA. RESULTS: Approximately 8.5% of participants at the first
      prison, and 8.3% at the second prison had a positive urine result, vaginal swab
      result or both, for a combined prevalence of 8.5%. Using positivity in either
      specimen as the reference standard, urine polymerase chain reaction had a
      sensitivity of 66.7% and vaginal swab polymerase chain reaction had a sensitivity
      of 84.4%. The only significant positive correlate of T. vaginalis infection was
      lower household income before arrest. Other variables nonsignificantly positively
      correlated with T. vaginalis were being employed at the time of arrest, having
      experienced sexual, physical, or emotional abuse by a family member, having a
      parent who had not had a drug or alcohol addiction, never exchanging sex for
      money or drugs, ever being pregnant, having abnormal vaginal bleeding/spotting,
      and having concurrent chlamydia or gonorrhea. CONCLUSIONS: Although not as high
      as in other studies of women entering US jails and state prisons, our observed T.
      vaginalis prevalence of 8.5% was much higher than in the general US population.
      Therefore, screening for T. vaginalis infection may be warranted at federal
      prison entry, as well as sexual health education during prison stay.

PMID- 20803781
TI  - Benzalkonium chloride causes colposcopic changes and increased susceptibility to
      genital herpes infection in mice.
AB  - BACKGROUND: Colposcopy is widely used in clinical microbicide safety testing but
      not in preclinical small animal studies. Endoscopic colposcopy could be employed
      in small animals allowing colposcopy to be used as one component in a
      multifactorial safety testing paradigm. STUDY DESIGN: We conducted dose-response
      studies in mice using 2%, 0.2%, or 0.02% benzalkonium chloride (BZK) as the test
      compound, and using multiple safety end points that included endoscopic
      colposcopy, susceptibility to vaginal HSV-2 infection, histology, and entry of
      inflammatory cells into the vagina. RESULTS: Animals treated with 0.2% or higher
      BZK experienced vaginal toxicities detectable by all tests used including
      colposcopy. In contrast, 0.02% BZK produced no significant changes except by
      histology in which a significant thinning of the vaginal epithelium was seen.
      CONCLUSION: Endoscopic colposcopy detected microbicide-elicited changes in the
      mouse vagina with similar sensitivity to the other endpoints used in these
      studies and would appear to be useful as part of a multifactorial microbicide
      safety testing paradigm in mice.

PMID- 20803785
TI  - Effects of tramadol and buprenorphine on select immunologic factors in a cecal
      ligation and puncture model.
AB  - Sepsis research relies on animal models. The models that most closely resemble
      clinical disease, such as cecal ligation and puncture, require surgery. After
      surgery, analgesics may not be included in experimental protocols because of
      concern over effects on inflammatory responses. This often generates animal
      welfare controversies within institutions; however, there are no scientific
      studies directly addressing the effects of analgesics on surgical models of
      sepsis. The purpose of this study was to characterize the effects of opioids on
      key parameters used in sepsis research.Female ICR mice were divided into four
      treatment groups (Ringer's lactate solution, high- or low-dose
      tramadol,buprenorphine) for 3-week mortality studies (n = 12 per treatment).
      Experimental groups were then repeated, and mice were killed at 12, 24, and 48 h
      postsurgery for cell counts, differentials, and cytokine levels in blood,
      peritoneum, and airways. Mortality studies demonstrated no significant
      differences between controls and any treatment group. However,significant
      differences were noted between buprenorphine and high-dose tramadol, revealing
      more and later deaths with tramadol. For comparison of immune parameters, Mann
      Whitney U or Student t test was performed, emphasizing comparisons between
      treatment and control. Although several results were significant, comparisons
      between control and any treatment group yielded no differences that remained
      consistently apparent during the observation period. Again,differences were
      observed between the treatments. The results suggest that judicious and limited
      use of some analgesics may not dramatically affect the outcome of similarly
      conducted cecal ligation and puncture studies when compared with those not using
      analgesics. However, when different analgesics are used, comparisons between
      studies may be complicated.

PMID- 20803786
TI  - Neurodegenerative disease: The missing link.

PMID- 20803787
TI  - Neurogenomics: Parental influences run deep.

PMID- 20803789
TI  - Neurodegenerative disease: microRNAs under threat from LRRK2.

PMID- 20803790
TI  - Neuron-glia interactions: A tunnel signal.

PMID- 20803791
TI  - Multiple sclerosis: Putting a dampener on inflammation.

PMID- 20803792
TI  - Neuron-glia interactions: Astrocytes in the air.

PMID- 20803788
TI  - Impact of anesthesia, analgesia, and euthanasia technique on the inflammatory
      cytokine profile in a rodent model of severe burn injury.
AB  - Anesthetics used in burn and trauma animal models may be influencing results by
      modulating inflammatory and acute-phase responses. Accordingly, we determined the
      effects of various anesthetics, analgesia, and euthanasia techniques in a rodent
      burn model. Isoflurane (ISO), ketamine-xylazine (KX), or pentobarbital (PEN) with
      or without buprenorphine were administered before scald-burn in 72 rats that were
      euthanized without anesthesia by decapitation after 24 h and compared with
      unburned shams. In a second experiment, 120 rats underwent the same scald-burn
      injury using KX, and 24 h later were euthanized under anesthesia or carbon
      dioxide (CO2). In addition, we compared euthanasia by exsanguination with that of
      decapitation. Serum cytokine levels were determined by an enzyme-linked
      immunosorbent assay. In the first experiment, ISO was associated with elevation
      of cytokine-induced neutrophil chemoattractant 2 (CINC-2) and monocyte
      chemotactic protein 1 (MCP-1), and KX and PEN was associated with elevation of
      CINC-1,CINC-2, IL-6, and MCP-1. Pentobarbital also decreased IL-1". IL-6
      increased significantly when ISO or PEN were combined with buprenorphine. In the
      second experiment, euthanasia performed by exsanguination under ISO was
      associated with reduced levels of IL-1", CINC-1, CINC-2, and MCP-1, whereas KX
      reduced CINC-2 and increased IL-6 levels. Meanwhile, PEN reduced levels of IL-1"
      and MCP-1, and CO2 reduced CINC-2 and MCP-1. In addition,decapitation after KX,
      PEN, or CO2 decreased IL-1" and MCP-1, although we found no significant
      difference between ISO and controls. Euthanasia by exsanguination compared with
      decapitation using the same agent also led to modulation of several cytokines.
      Differential expression of inflammatory markers with the use of anesthetics and
      analgesics should be considered when designing animal studies and interpreting
      results because these seem to have a significant modulating impact. Our findings
      indicate that brief anesthesia with ISO immediately before euthanasia by
      decapitation exerted the least dampening effect on the cytokines measured.
      Conversely, KX with buprenorphine may offer a better balance during longer
      procedures to avoid significant modulation. Standardization across all
      experiments that are compared and awareness of these findings are essential for
      those investigating the pathophysiology of inflammation in animal models.

PMID- 20803793
TI  - Synaptic plasticity: Assertive authorities.

PMID- 20803794
TI  - Neuroendocrinology: Housing conditions affect tumour growth.

PMID- 20803795
TI  - The significance of the Druckrey-Kupfmuller equation for risk assessment--the
      toxicity of neonicotinoid insecticides to arthropods is reinforced by exposure
      time.
AB  - The essence of the Druckrey-Kupfmuller equation dtn = constant (where d = daily
      dose and t = exposure time-to-effect, with n > 1) for chemical carcinogens is
      that the total dose required to produce the same effect decreases with decreasing
      exposure levels, even though the exposure times required to produce the same
      effect increase with decreasing exposure levels. Druckrey and Kupfmuller inferred
      that if both receptor binding and the effect are irreversible, exposure time
      would reinforce the effect. The Druckrey-Kupfmuller equation explains why
      toxicity may occur after prolonged exposure to very low toxicant levels.
      Recently, similar dose-response characteristics have been established for the
      toxicity of the neonicotinoid insecticides imidacloprid and thiacloprid to
      arthropods. This observation is highly relevant for environmental risk
      assessment. Traditional approaches that consider toxic effects at fixed exposure
      times are unable to allow extrapolation from measured endpoints to effects that
      may occur at other times of exposure. Time-to-effect approaches that provide
      information on the doses and exposure times needed to produce toxic effects on
      tested organisms are required for prediction of toxic effects for any combination
      of concentration and time in the environment.

PMID- 20803796
TI  - [Conceptual framework for integrating reproductive health in school: experience
      in Senegal].
AB  - OBJECTIVE: Adolescent reproductive health is a public health concern. The
      objective of this article is to report the conceptual framework for integrating
      reproductive health services in school from a pilot project carried out in
      Senegal. MATERIALS AND METHODS: A 10-year strategic plan from 2000 to 2010 for
      education and training has been established by the Ministry of Education and the
      component related to health and nutrition has been in charge by the medical
      health control division (DCMS). By putting into action the strategy of this
      component, a pilot project for integrating reproductive health in school had been
      set up and carried out from 2002 to 2006. This project was held within a
      secondary grade school and in a health structure especially designated for
      students. RESULTS: School health policy established by the Ministry of Education
      and the choice of the DCMS as the institutional leadership has helped to define a
      framework for synergic interventions directed to school-aged children. Thus, the
      coordination team with health experts has carried out the project held through a
      participatory process and advocacy since its conception phase putting together
      the authority of the Ministry, the school-aged children, the teachers and the
      parents. Capacities strengthening of different stakeholders through training,
      sensibilisation and information have been made with partnership development and a
      signed protocol between the Ministry of Education and the Ministry of Health.
      CONCLUSION: The magnitude of adolescent reproductive health problems justifies
      the integration of reproductive health services in school.

PMID- 20803797
TI  - Reproductive endocrinology: Testosterone-replacement therapy in older men with
      limited mobility: is it safe?

PMID- 20803798
TI  - Nutrition: Giving vitamin A supplements to mothers has lasting benefits for their
      offspring.

PMID- 20803799
TI  - Pharmacotherapy: Increased stroke risk associated with osteoporosis drugs.

PMID- 20803800
TI  - Thyroid function: Sorafenib alters metabolism of T3.

PMID- 20803801
TI  - Metabolic risk and neck fat.

PMID- 20803802
TI  - Diabetes: Low-intensity physical activity for prevention of diabetes mellitus in
      old age.

PMID- 20803803
TI  - Bone: High 27-hydroxycholesterol decreases BMD.

PMID- 20803804
TI  - Surgery: Intraoperative parathyroid hormone monitoring: yes or no?

PMID- 20803806
TI  - Cancer: Oncofetal fibronectin mRNA and papillary thyroid cancer.

PMID- 20803805
TI  - Citalopram for hot flashes.

PMID- 20803807
TI  - Proteomics: A discovery strategy for novel cancer biomarkers.

PMID- 20803808
TI  - Tumorigenesis: Ground zero.

PMID- 20803809
TI  - Tumorigenesis: To the death!

PMID- 20803810
TI  - Therapy: Lethal cycling.

PMID- 20803811
TI  - Genomics: A broad brush.

PMID- 20803812
TI  - Macroenvironment: Stimulating resistance.

PMID- 20803813
TI  - Leukaemia: Comfortably MSI2-NUMB.

PMID- 20803814
TI  - Hypoxia: The HIF2alpha puzzle.

PMID- 20803815
TI  - The benefit of labor induction for preeclampsia beyond 37 weeks' gestation.

PMID- 20803817
TI  - Respiratory morbidity in adulthood after respiratory syncytial virus
      hospitalization in infancy.
AB  - A prospective >25-year follow-up study evaluated the outcome of patients
      hospitalized for respiratory syncytial virus (RSV) infection at <24 months of
      age. Questionnaires were sent to 51 study subjects and to population controls.
      Self-reported asthma was present in 30% of the former RSV patients, compared with
      3.8% of controls. In adjusted analyses, RSV hospitalization was an independent
      risk factor of adulthood asthma.

PMID- 20803816
TI  - [Healthy nutrition: steering with taxes?].

PMID- 20803818
TI  - A letter to future physicians: One dozen important things you might not learn
      enough about during medical training--but should.

PMID- 20803819
TI  - CQ sources/bibliography.

PMID- 20803820
TI  - How sustained is sustained viral response in patients with hepatitis C virus
      infection?
AB  - BACKGROUND: Sustained virological response (SVR) is achieved in a high proportion
      of patients with chronic hepatitis C infection, particularly those with genotype
      2 or 3 HCV infection. However, data on long-term durability of virological
      response in patients who achieve SVR are limited. AIM: To evaluate the long-term
      durability of virological response in patients who have achieved SVR with
      interferon-based combination therapy. METHODS: One hundred patients with chronic
      HCV infection who had obtained SVR after IFN and ribavirin combination therapy
      were followed up for up to 8 years with annual HCV RNA testing. RESULTS: During a
      followed up of 6 months to 8 years, 8 of 100 patients with initial SVR developed
      late relapse of HCV infection. Relapse was more common in patients who had
      cirrhosis (5/28 [18%] vs. (3/72 [4%] with no cirrhosis; p=0.037). CONCLUSION: SVR
      is durable in most patients, but some patients do have late relapse; long term
      follow up may be particularly important in a subset of patients with HCV
      infection who have liver cirrhosis.

PMID- 20803821
TI  - Nephrotic syndrome with pegylated interferon alfa 2a and ribavirin for a patient
      with chronic hepatitis C.

PMID- 20803822
TI  - Does plasma resistin level have a role in predicting inflammatory bowel disease
      activity?

PMID- 20803823
TI  - [Retreat is questionable].

PMID- 20803824
TI  - [Between medical and paramedical, "intermediate" professions under study].

PMID- 20803825
TI  - [Propositions about refusing to care at the National Conference of Health].

PMID- 20803826
TI  - [The journeys of patients and palliative nurses].

PMID- 20803827
TI  - [Mutual National Insurance probes its supporters and social protection].

PMID- 20803828
TI  - Preparing clinical laboratory science students with teaching skills.
AB  - Training clinical laboratory science (CLS) students in techniques of preparation
      and delivery of an instructional unit is an important component of all CLS
      education programs and required by the national accrediting agency. Participants
      of this study included students admitted to the CLS program at Northern Illinois
      University and enrolled in the teaching course offered once a year between the
      years of 1997 and 2009. Courses on the topic of "teaching" may be regarded by CLS
      students as unnecessary. However, entry level practitioners are being recruited
      to serve as clinical instructors soon after entering the workforce. Evaluation of
      the data collected indicates that students are better prepared to complete tasks
      related to instruction of a topic after having an opportunity to study and
      practice skills of teaching. Mentoring CLS students toward the career role of
      clinical instructor or professor is important to maintaining the workforce.

PMID- 20803829
TI  - Growing our own: teaching and doing research in CLS.
AB  - The shortage of clinical laboratory scientists (CLS) has been well-documented in
      the healthcare environment. This growing concern only becomes more critical as we
      enter the retiring baby boomer era in our society. Concomitantly, the problem of
      addressing how university CLS programs recruit and retain faculty to teach and
      satisfy research agendas is not being studied. These two problems, if allowed to
      collide, will provide a "perfect storm" with serious implications for an ongoing
      shortage of personnel and overall quality for the profession. CLS faculty, in the
      university setting, must typically satisfy the three tenets for tenure and
      promotion - teaching, scholarship, and service. While teaching and service will
      always be critical, scholarship (research) is an area of expertise that must be
      "taught" and mentored for future CLS faculty to be successful in the very real
      arena of "publish or perish". This article provides a commentary with specific
      details associated with our experience in offering an evolving dedicated CLS
      clinical research course to purposively "grow our own" students in the art of
      conducting successful research. It offers a flexible template for adapting or
      incorporating a lecture and laboratory course to address theoretical and
      practical knowledge in the realm of clinical research. Additionally, a discussion
      of other research mentoring activities in our program will be outlined. The long
      term goal (and hope) of these program objectives is to build a culture of
      research for current faculty and for CLS graduates. This paper provides an
      approach to embedding these research ideals in all CLS graduates and,
      importantly, an intentional attempt to create a mindset for a possible career as
      a future CLS faculty member who can be successful in both the university and
      clinical environment.

PMID- 20803830
TI  - Preparing CLS professionals to be consumers and producers of research.
AB  - Research proficiency is part of the curriculum in all NAACLS accredited CLS
      programs. Learning the basic research tools enables students to understand and
      interpret published research as informed consumers of research. This paper
      describes an improved and innovative approach to prepare future CLS professionals
      to be both analytical consumers and active producers of pertinent research.

PMID- 20803831
TI  - Professionalism--a required CLS/CLT curricular component.
AB  - OBJECTIVE: Determine the impact of requiring Clinical Laboratory Science (CLS)
      students to participate in approved professionalism activities as part of a
      mandatory management course. DESIGN: Quasi-experimental, case study reporting
      qualitative results of 25 CLS students. During the admission interview, students
      complete a written response to questions about their perceptions related to
      professionalism. During the clinical educational year, students are required to
      complete approved professionalism activities as part of a management course. At
      the end of the course, students write a reflective paper focusing on their
      professional activities and how these experiences will influence their future
      professional practice. Overall themes of student reflections are provided.
      SETTING: University of Nebraska Medical Center (UNMC) CLS Program in Omaha.
      CONCLUSION: After participating in a mandatory professionalism curricular
      component requiring active student participation in professional activities,
      student reflective writings provide evidence this is one successful approach to
      nurture professional identity within future Clinical Laboratory Science/Clinical
      Laboratory Technician (CLS/CLT) practitioners.

PMID- 20803832
TI  - Research and scholarship of clinical laboratory science faculty members.
AB  - OBJECTIVES: To describe the research and scholarly productivity of faculty in
      four-year college and university clinical laboratory science (CLS) programs. To
      identify hours spent in research, numbers of presentations and publications, and
      external funding. DESIGN: In 2008, a national study involving 106 college and
      university CLS programs was conducted to determine whether faculty were
      participating in research. A questionnaire, in electronic format, was distributed
      to 448 faculty members. Data from 2001 to 2008, and from 275 respondents (61%
      response) representing 93 of 106 (88%) CLS programs were analyzed. SETTING: The
      study took place at The Ohio State University with collaboration from the
      University of Minnesota. PARTICIPANTS: All CLS faculty within a four-year
      university or college sponsoring a NAACLS-accredited CLS program were invited to
      participate. MAIN OUTCOME MEASURES: To determine whether CLS faculty scholarly
      activities have been strengthened in the past decade. To quantitate scholarship
      productivity. To assess faculty perceptions of their employment environments.
      RESULTS: Data indicate that faculty who possess earned doctorates have higher
      levels of research productivity. While 52% of CLS faculty hold doctorates and 45%
      are tenured, 36% of all CLS faculty members have not published a research paper
      or abstract since 2001. On the other hand, 19% have published 11 or more times.
      CLS faculty were also awarded a total of $62 million in external funding, 83%
      from government sources. Teaching remains a primary responsibility of many
      faculty members. CONCLUSIONS: In the past decade, and generally speaking, CLS
      faculty have made some progress in scholarship including highest degree obtained,
      publications, presentations, and grantsmanship.

PMID- 20803833
TI  - An exploratory study of live vs. web-based delivery of a phlebotomy program.
AB  - Changes in student population and increased Web-based education offerings
      provided the impetus to assess pedagogy, cognitive outcomes and perceptions of
      course quality. OBJECTIVE: This study explored cognitive outcomes and students'
      perception of course quality related to the Seven Principles for Good Practice in
      Undergraduate Education between live classroom delivery, compared to a Web-based
      delivery of a phlebotomy program. DESIGN: Quasi-experimental; students self
      selected to enroll in live or Web-based program. RESULTS: For cognitive outcomes,
      no significant difference was found between the groups. Student perception of
      course quality differed only for Principle One (student-instructor contact).
      Students in the live classroom rated Principle One higher for the Part I course
      compared to the Web-based group. For the Part II course, there was no significant
      difference in perception of course quality related to any of the Seven
      Principles. CONCLUSIONS: The more constructivist pedagogy in the Part II course
      did not improve cognitive outcomes however, it may have contributed to knowledge
      retention. The live group rated Principle One in the Part II course evaluation
      relatively the same as they did for the Part I course evaluation. However, the
      Web-based group rated Principle One considerable higher for the Part II course
      than for Part I course. Future studies with a larger sample could explore
      improved course quality assessment instruments.

PMID- 20803834
TI  - A typology of evidence based practice research heuristics for clinical laboratory
      science curricula.
AB  - A typology of EBP research heuristics was defined relative to clinical laboratory
      science levels of practice. Research skills requisite for CLS baccalaureate level
      are associated mainly with quality control of analytic processes. Research skills
      at master's level are associated with pre- and post-analytic investigations, as
      well. Doctoral level CLS practice portends to utilize research skills
      facilitating quality investigations at the systems level.

PMID- 20803835
TI  - Focus: online education and technology introduction.

PMID- 20803836
TI  - Staying connected: online education engagement and retention using educational
      technology tools.
AB  - The objective of this article is to inform educators about the use of currently
      available educational technology tools to promote student retention, engagement
      and interaction in online courses. Educational technology tools include content
      management systems, podcasts, video lecture capture technology and electronic
      discussion boards. Successful use of educational technology tools requires
      planning, organization and use of effective learning strategies.

PMID- 20803837
TI  - Preparing online students for comprehensive examinations.
AB  - OBJECTIVE: Identify and remedy difficulties in the preparation of online students
      for certification examination success. DESIGN: The final examination scores for
      the CLS Seminar course for the 2008 class of 27 on-campus and 10 online students
      were compared for statistical differences in seven examination areas. Problem
      areas were identified and changes in the CLS Seminar course were made in 2009 to
      improve the scores of the online students. The examination scores for the 2009
      class of 33 on-campus and 10 online students were studied to determine
      improvement. Student's two-tailed t-test was used to determine statistical
      significance of differences between scores of on-campus and online students.
      INTERVENTIONS: Interactive video over the web; used to answer online student
      questions, review games, more class time, and more recorded review sessions; were
      added to the Seminar. The study guides provided during preceptorships were tied
      to the objectives of the seminar course and the questions on examinations.
      Specific objectives for each question missed on the final examinations were
      provided to the student. RESULTS: In 2008, examination scores for online students
      were lower in two of seven areas by a statistically significant amount than on
      campus students. The difference approached significance in a third area. After
      interventions in 2009, the examinations scores had equalized with the exception
      of one area, Immunology. CONCLUSION: Increasing the amount and method of review
      in areas deemed important to online education was successful in improving
      examination scores.

PMID- 20803838
TI  - [Turkish Society of Cardiology Ethics Manual].

PMID- 20803839
TI  - Comparison between single-step and balloon dilatational tracheostomy.

PMID- 20803840
TI  - Primary heart graft failure.

PMID- 20803841
TI  - Transplacental transport of IgG antibodies specific for pertussis, diphtheria,
      tetanus, haemophilus influenzae type b, and Neisseria meningitidis serogroup C is
      lower in preterm compared with term infants.
AB  - BACKGROUND: Maternal antibodies, transported through the placenta during
      pregnancy, contribute to the protection of infants from infectious diseases
      during the first months of life. The aim of this study was to measure the
      concentration of antibodies against several vaccine-preventable diseases in
      paired maternal and cord blood serum samples in preterm and term infants and to
      assess placental transfer ratios and infant antibody concentrations against
      vaccine-preventable diseases. METHODS: Antibody concentrations specific against
      pertussis proteins (pertussis toxin, filamentous hemagglutinin, pertactin, and
      fimbriae), diphtheria and tetanus toxins, and antibody concentrations specific
      against polysaccharides from Haemophilus influenzae type b and Neisseria
      meningitidis serogroup C were measured in cord blood samples from preterm (<32
      weeks and 1500 g) and term infants and maternal serum samples, using a
      fluorescent bead-based multiplex immunoassay. RESULTS: A total of 96 preterm and
      42 term infants and their mothers were included in the study. Placental transfer
      ratios of antibodies against all vaccine antigens were significantly lower in
      preterm infants (medians varied from 0.26 to 0.86) compared with term infants
      (medians, 0.74-1.89; all antibodies P < 0.05). Furthermore, polysaccharide
      vaccine-specific antibodies showed lower transplacental transport ratios than
      protein-vaccine-specific antibodies. Maternal concentrations are the most
      important determinants of infant antibody concentrations against vaccine
      preventable diseases. CONCLUSIONS: Preterm infants benefit to a lesser extent
      from maternal antibodies against vaccine-preventable diseases than term infants,
      posing them at higher risk for infectious diseases in the first months of life.

PMID- 20803842
TI  - Stroke After varicella-zoster infection: report of a case and review of the
      literature.
AB  - Ischemic stroke is a recognized complication of varicella-zoster virus
      infections. We report on an immunocompetent 5-year-old girl who presented with
      acute neurologic deficits attributed to cerebral infarction, 3 months after
      varicella-zoster virus infection. Magnetic resonance imaging of the brain showed
      subacute ischemic lesions in the territory of the right middle cerebral artery. A
      literature review of 70 similar cases is reported.

PMID- 20803843
TI  - Banding in Bangkok, CABG in Calcutta: the United States physician and the growing
      field of medical tourism.

PMID- 20803844
TI  - Black nurse, White nurse: Heroines and the horrors of the Crimean War.

PMID- 20803846
TI  - Research for health equity: knowing is not enough.

PMID- 20803845
TI  - Fritz Juliusberg (1872-1939): his life and achievements in dermatology.

PMID- 20803847
TI  - Wave length and action potentials: history of the International Federation of
      Clinical Neurophysiology.

PMID- 20803848
TI  - Can we minimize hypotension following spinal anesthesia for cesarean section?

PMID- 20803849
TI  - Psoriasis and anesthetic considerations.
AB  - Psoriasis can be extremely debilitating for the patient due to the fact that it
      can affect the whole integument, and, because of its chronic nature, can afflict
      the individual for most of his/her life. In some cases such as erythrodermic
      psoriasis, the disease can even be fatal due to complications such as high-output
      congestive heart failure. The anesthesiologist must take many factors into
      consideration such as the severity of the disease, where to place regional
      anesthesia, and the anesthetic complications associated with certain types of
      psoriatic medications. Although certain mechanisms such as differentiating
      keratinocytes while impeding their proliferation, immunosuppressive therapy,
      regulating transcription via steroids and the use of extra-cellular oxygen
      radicals have been used to manage psoriasis, no "miracle" cure exists. Even
      though psoriasis is usually treated by dermatologists, anesthesiologists must be
      careful and prepared because the disease is chronic, variable, and patients must
      be carefully handled in the operating room.

PMID- 20803850
TI  - Production pressure, medical errors, and the pre-anesthesia checkout.
AB  - Medical errors have rightly become an important societal and professional issue.
      While anesthesiology as a specialty has been at the forefront of the patient
      safety movement it is also subject to the same pressures for efficiency as any
      other business. Whether this pressure is at odds with the delivery of safe care
      is not yet clearly delineated. However, a theoretical framework of unsafe
      practices as well as a body of literature from other industries such as aviation
      suggests that production pressure may lead to unsafe practice. Also, it is
      unlikely that the common pressures encountered in the operating room (e.g., to
      reduce turnover times) have any positive financial impact for anesthesiology
      departments unless extra cases can be done each day. We include in this review a
      potential area for improvement and further research for anesthesiologists, the
      preanesthesia induction timeout. This crucial period of any anesthetic involves a
      high workload and is often the most hurried; this combination may be setting
      practitioners up to make errors. We suggest the use of checklists and timeouts to
      formalize this period and propose a useful seven-point list of crucial items and
      events needed before each anesthetic.

PMID- 20803851
TI  - Visual loss after anesthesia different causes: different solutions--a review.

PMID- 20803852
TI  - Preanesthetic assessment of the patient with hepatocellular carcinoma.

PMID- 20803853
TI  - Intensive insulin therapy versus conventional insulin therapy for critically ill
      trauma patients admitted to ICU.
AB  - PURPOSE: The objective of our study was to evaluate the beneficial effect of IIT
      in reducing mortality and morbidity in critically ill trauma patients admitted to
      ICU. METHOD AND MATERIAL: Nested cohort study within a Randomized Controlled
      Trial. All trauma patients with GCS < or = 9 included in the original trial were
      included in this study. Primary outcome was ICU mortality. RESULT: There was no
      difference in ICU mortality between IIT and CIT groups (6.5% vs. 5.5%, p = 0.67).
      After adjustment for baseline characteristics, IIT therapy was also not
      associated with mortality (Adjusted Hazard Ratio 1.33, 95% CI 0.35-5.05). IIT
      therapy was associated with a significant increase in the incidence of
      hypoglycemia as compared to CIT, at least one hypoglycemia episode occurred in
      18.5% of patients in IIT and 1.3% in the CIT group (P < 0.0001). CONCLUSION: IIT
      was not associated with survival improvement in trauma patients admitted to ICU
      and was associated with increased incidence of hypoglycemia.

PMID- 20803854
TI  - Combined use of crystalloid preload and low dose spinal anesthesia for preventing
      hypotension in spinal anesthesia for cesarean delivery: a randomized controlled
      trial.
AB  - BACKGROUND AND OBJECTIVE: Spinal anaesthesia for caesarean section is commonly
      associated with hypotension and crystalloid preload is widely recommended. Low
      dose spinal appears to cause less hypotension. The aim of this study was to
      investigate whether the combined use of crystalloid preload and low dose spinal
      anaesthesia might further reduce the rates of hypotension. METHODS: Sixty-two
      patients were randomly assigned to two groups: crystalloid preload anaesthesia
      (P): received a rapid infusion of 20 mL/kg lactated Ringer's solution (LR), and
      no preload anaesthesia (N). The incidence of hypotension and the amount of
      ephedrine used to treat it were compared. Spinal anaesthesia was performed with
      0.5% isobaric bupivacaine 7.5 mg and fentanyl 10 microg and morphine 100 microg.
      RESULTS: The incidence of hypotension was similar in the P and N groups. Same
      doses of ephedrine were required to treat hypotension in the two groups.
      CONCLUSION: Crystalloid preload combined with low-dose spinal anaesthesia do not
      reduce the incidence of hypotension nor its severity.

PMID- 20803855
TI  - Reduction of bupivacaine dose in spinal anaesthesia for caesarean section may
      improve maternal satisfaction by reducing incidence of low blood pressure
      episodes.
AB  - BACKGROUND: Spinal anaesthesia for caesarean section exposes to high incidence of
      arterial hypotension which can result in maternal and neonatal morbidity. We
      hypothesized that the reduction of this dose from 10 mg to 7.5 mg would minimize
      hypotension without altering pain relief. METHODS: In this double-blind
      prospective study, 80 ASA1 women scheduled for elective caesarean section were
      randomized into two groups A and B receiving respectively 10 and 7.5 mg of
      isobaric bupivacaine both with 25 microg of fentanyl and 100 microg of morphine
      in spinal anaesthesia. Intravenous ephedrine was administered for each episode of
      hypotension. We recorded sensory and motor block, intraoperative pain, nausea and
      vomiting. In postanaesthesia care unit, sensory and motor recoveries were
      measured and maternal satisfaction rate was assessed. RESULTS: In group A, a
      larger dose of ephedrine was needed (32 +/- 23 vs 19 +/- 16 mg; p = 0.004).
      Incidence of sensory block above T4 (52 vs 10%; p < 0.001), nausea (52 vs 22%; p
      = 0.005) and vomiting (25 vs 8%; p = 0.03) were all higher than in group B.
      Arterial hypotension was less frequent in group B (68 vs 88%; p = 0.03). The time
      required for recovery to T10 sensory level and motor regression were shorter than
      in group A (p < 0.001) and the satisfaction rate was higher than in group A
      (excellent and good in 90% vs 67%; p = 0.03). There was no difference in pain
      relief. CONCLUSION: A dose of 7.5 mg of isobaric bupivacaine reduced incidence of
      hypotension, nausea and vomiting and improved patient satisfaction.

PMID- 20803856
TI  - The impact of long-lasting preemptive epidural analgesia before total hip
      replacement on the hormonal stress response. A prospective, randomized, double
      blind study.
AB  - Recent studies suggest that preemptive analgesia may be effective in reducing
      postoperative pain. One physiologic explanation may be interference with the
      endogenous opioid response. We investigated whether long-lasting preoperative
      preemptive analgesia may have an effect on the hormonal stress response after
      total hip replacement. METHODS: 42 patients scheduled for elective hip
      replacement for coxarthrosis were randomized to receive, on the day before the
      operation, either 5 ml*h(-1) ropivacaine 0.2% (study group, n = 21) or 5 ml*h(-1)
      saline (control group, n = 21). Postoperative analgesia was achieved in both
      groups by patient-controlled epidural analgesia (PCEA) with ropivacaine 0.2%. The
      main outcome measure was the concentration of authentic beta-endorphin [1-31] in
      plasma up to 4 days after surgery. Additional parameters included concentrations
      of adrenocorticotrope hormone and cortisol. RESULTS: Both groups were comparable
      concerning preoperative parameters and pain scores. Epidural blocks were
      sufficient in all patients for operative analgesia. Preemptive analgesia was
      performed for 11-20 hours in both groups and led to significantly decreased pain
      scores before surgery. Preemptive analgesia with epidural ropivacaine did not
      lead to decreased concentrations of beta-endorphin [1-31] before the start of
      surgery or in the postoperative period. Furthermore, no differences could be
      detected in the time course of beta-endorphin and adrenocorticotrope hormone
      after surgery. However, cortisol concentrations differed significantly between
      groups before the operation, but showed a comparable rise after surgery.
      CONCLUSION: Differences in postoperative pain after preemptive analgesia do not
      seem to be due to an altered endogenous opioid response.

PMID- 20803857
TI  - Prevention of postoperative psychic trauma in children the role of the anesthetic
      and surgical approach.

PMID- 20803858
TI  - The effect of oral clonidine premedication on nausea and vomiting after ear
      surgery.
AB  - OBJECTIVE: Postoperative nausea and vomiting (PONV) is a most distressing adverse
      event for surgical patients with a considerable economic impact .The aim of the
      present study was to evaluate the effect of clonidine given orally for PONV in
      patients undergoing anesthesia for outpatient ear surgery. METHODS: Sixty
      patients 30.2 +/- 9.9 years, scheduled for ear surgery, were randomly assigned to
      one of two groups (clonidine or placebo) in a double-blinded manner. Anesthesia
      was standardized laryngeal mask airway, fentanyl, propofol, halothane, nitrous
      oxide. RESULTS: A complete response, defined as no PONV and no need for rescue
      antiemetic medication, during the first 24 h after anesthesia was 33% with
      placebo and 67% with clonidine, respectively (P. 0.01). No clinically adverse
      event was observed in any of the groups. CONCLUSION: Oral premedication with
      clonidine reduced the rate of PONV in patients undergoing outpatient ear surgery.

PMID- 20803859
TI  - Continuous sciatic nerve block: compartive study between the parasacral, lateral,
      and anterior approaches for lower limb surgery.
AB  - OBJECTIVE: The aim of the present study was to evaluate the ease and reliability
      of the anterior and lateral approaches to sciatic nerve block compared to the
      posterior parasacral approach, and their suitability for the specific factors in
      the patients, positions, and surgeries. Also, the insertion and usefulness of the
      continuous catheter technique was evaluated. METHODS: The study was carried out
      on 120 patients, ASA I, II and III, of both genders, age range between 20 and 70
      years, scheduled for orthopedic, general and vascular lower limb surgery.
      Patients were enrolled in a prospective, randomized, double blind study. Patients
      were divided into three equal groups, 40 patients each. All the patients received
      femoral nerve block in addition to sciatic nerve block either parasacral
      (Posterior group), lateral (Lateral group) or anterior approach (Anterior group).
      This was followed by continuous femoral and sciatic nerve blocks in the
      postoperative period. Patients were assessed as regards the time, duration and
      intensity of the sensory and motor blocks and also the postoperative analgesia
      offered by the continuous block. They were also assessed for the hemodynamic
      changes accompanied these blocks. Radiological study was made to demonestrate the
      spread of different volumes of the drugs alongside the course of the sciatic
      nerve. RESULTS: The posterior parasacral approach is the easiest technique to
      perform and used successfully even in obese patients, but difficult to be done,
      if at all, in patients with limited movement such as multi-pelvic fractures. The
      anterior approach was found to be the best for the patients in the supine
      position, with best results as regards patients' satisfaction and sensory and
      motor blocks. Only, it is a technique that needs high experience especially in
      obese patients. The lateral approach was the least performed technique especially
      its high approach. However, it is useful in patients in supine position, and
      gives the best results in thin patients. The technique showed to be extremely
      difficult in obese patients. CONCLUSION: The insertion of a catheter for
      continuous nerve block was easy. These blocks provided good or excellent
      postoperative analgesia for all patients in the different groups and facilitated
      early mobilization which helped in preventing the lower limb srugery - related
      morbidity and mortality.

PMID- 20803860
TI  - Comparison of the effects of intrathecal different dosage of levobupivacaine in
      elective day-case arthroscopy of the knee.
AB  - BACKGROUND AND OBJECTIVES: To observe the motor and sensorial block
      characteristics with different dosage of levobupivacaine during spinal block for
      the patients undergoing day-case knee arthroscopy. MATERIAL AND METHOD: Eighty,
      80 ASA physical status I-II patients, undergoing day-case knee arthroscopy
      received 0.5% levobupivacaine; 7.5 mg in Group I, 10 mg in Group II, 12.5 mg in
      Group III and 15 mg in Group IV for spinal anesthesia. Maximum sensorial and
      motor block levels, sensorial and motor block durations, time to required
      readiness to surgery after block and side effects were recorded. RESULTS: The
      time required to achieve readiness to surgery was longest and mean duration of
      sensory and motor block was shortest in Group I. The groups were similar in
      regards to the number of failed blocks requiring general anaesthesia (p > 0.05).
      First micturition and unassisted ambulation with crutches times were shortest in
      Group I (p < 0.01). Home discharge and first additional analgesic request time
      were similar in four group (p > 0.05). CONCLUSION: The motor and sensorial block
      obtained with different spinal anesthesia dosages of 0.5% levobupivacaine were
      effective for day-case knee artroscopy. Although 7.5 mg is suitable for patients;
      10, 12.5 and 15 mg could be used according to anesthetist experience without any
      side effects.

PMID- 20803861
TI  - Study of post dural puncture headache with 27G Quincke & Whitacre needles in
      obstetrics/non obstetrics patients.
AB  - The proposed study was carried out in the department of Anaesthesiology,
      Intensive care & Pain management, Himalayan Institute of Medical Sciences. Swami
      Rama Nagar, Dehradun. A total of 120 patients of ASA I & II obstetric & non
      obstetric undergoing elective/emergency surgery under subarachnoid block were
      included under the study. AIM: To evaluate the frequency of PDPH during spinal
      anaesthesia using 27 gauge Quincke vs 27G whitacre needle in obstetric/non
      obstetric patient. OBSERVATION: In our study patients were in the age group of 15
      75 years. Most of the patients in our study belong to ASA Grade I. There was 2%,
      1%, 4% and 3% hypotension in-group A, B, C, D respectively. There was 2%, 4%
      shivering in-group A, C respectively and 1% each in group B, D. In our study
      failed spinal with 27G Quincke needle was in one case (3.33%) in-group C where
      successful subarachnoid was performed with a thicken spinal needle 23G Quincke.
      There was no incidence of PDPH in-group A and D, while 1 (2%) patient in-group B
      and 2 (4%) in group C. RESULTS: All the three patients were for lower section
      caesarean section and were young and had undergone more than one attempt to
      perform spinal block. The headache severity was from mild to moderate and no
      epidural blood patch was applied.

PMID- 20803862
TI  - Anaesthetic management of congenital laryngeal web presenting with acute upper
      airway obstruction.
AB  - This is a case of failed intubation in a child of 15 months due to presence of
      laryngeal web. The airway was maintained by Cole Neonatal tube size 2 mm held at
      the available orifice of the glottis with maintenance of spontaneous respiration
      under general anesthesia till emergency tracheostomy was performed.

PMID- 20803863
TI  - Epileptic seizure during anaesthesia induction with etomidate.
AB  - In this report a 20-year-old male patient who had suffered tonic-clonic seizure
      after a single induction dose of etomidate until a bispectral index value of 60
      is presented. Our best knowledge, this case is the first report of pure etomidate
      (with induction dose) induced generalized tonic clonic seizure proven with EEG.
      Anaesthesiologists should be careful against such a complication even in the
      induction stage of anaesthesia during etomidate use.

PMID- 20803864
TI  - Horner's syndrome after lumbar epidural analgesia during labor.
AB  - Horner's syndrome is rarely reported after epidural analgesia during labor. The
      use of Top-Up local anesthetic for controlling labor pain in the first stage of
      labor, or to dense the block in caesarean deliveries can result in this
      complication. We reported a cases of Horner's syndrome during epidural analgesia
      in labor in spite of not giving any Top-Up dose. The case was clinically evident
      and was successfully managed by stopping the epidural infusion, and reassuring
      the parturient as well as the family; until the disappearance of the signs and
      symptoms. The infusion was then restarted, delivery was uneventful and no
      consequent neurological or psychological problems were noticed after a one-month
      follow-up.

PMID- 20803865
TI  - Radiation induced hypopharyngeal stenosis masquerading as the larynx: a case
      report.
AB  - Radiation to the head and neck is commonly used in the treatment of cancers. A
      side effect in some patients is the development of pharyngeal and or esophageal
      strictures. Hypopharyngeal strictures can resemble edematous larynges. If
      mistakenly so identified, tracheal tubes placed through these structures are
      unlikely to result in tracheal intubation and more likely to cause obstruction,
      esophageal intubation or mediastinal damage. This report points out the
      development of hypopharyngeal stenosis following radiation. The location and
      appearance of hypopharyngeal stenosis during laryngoscopy are illustrated. The
      report points out the deficiencies of newer supraglotic laryngoscopes in this
      situation and underscores the benefits of flexible fiberoptic devices.

PMID- 20803866
TI  - Intraoperative airway obstruction related to tracheostomy tube malposition in a
      patient with achondroplasia and Jeune's syndrome.
AB  - A 14 year-old adolescent with achondroplasia and Jeune's syndrome (asphyxiating
      thoracic dystrophy) presented for cervical spine surgery in the prone position.
      Due to the need for home mechanical ventilation at night, the patient had a
      tracheostomy in place. With the first surgical procedure, the cuffed tracheostomy
      tube was left in place during prone positioning. Difficulties encountered with
      ventilation through the cuffed tracheostomy tube in the prone position
      necessitated aborting the case. During three subsequent surgeries, the
      tracheostomy tube was removed and an armored endotracheal tube was placed through
      the tracheostomy stoma prior to prone positioning. No further difficulties with
      ventilation were noted with the subsequent cases. There are currently no
      guidelines in the medical literature regarding perioperative management of
      patients with a tracheostomy requiring prone positioning for surgery. The
      management of such patients is reviewed and possible problems with tracheostomy
      positioning during prone positioning are explored. Given such issues, we would
      suggest removal of the tracheostomy tube and placement of an armored endotracheal
      tube through the stoma during surgical procedures in the prone position.

PMID- 20803867
TI  - Anesthetic management of a patient with hypertrophic obstructive cardiomyopathy
      undergoing modified radical mastectomy.
AB  - Hypertrophic obstructive cardiomyopathy (HOCM) is a rare genetic disorder
      characterized by left ventricular outflow tract (LVOT) obstruction. Clinical
      presentation ranges from absence of symptoms to sudden death. Our 60 year old
      patient scheduled for left modified radical mastectomy had HOCM since seventeen
      years with severe LVOT obstruction and mitral regurgitation. An implantable
      cardioverter defibrillator (ICD) and permanent pacemaker (PPM) was inserted 15
      months earlier for ventricular tachycardia. Anesthetic management of these
      patients presents considerable challenges and requires maintenance of desired
      hemodynamic parameters and management of specific complications. Factors like
      tachycardia, hypovolemia, vasodilation and increased cardiac contractility leads
      to exacerbation of the obstruction. In our patient there was the additional
      consideration of the ICD which required to be turned off during surgery with full
      provision for external defibrillation. We managed to successfully maintain the
      desired hemodynamics throughout the surgery and the patient was discharged home
      on the seventh postoperative day.

PMID- 20803868
TI  - The awake Glidescope intubation: an additional alternative to the difficult
      intubation.
AB  - BACKGROUND: The incidence of difficult intubations has consistently remained
      between 8 and 9%. We found a novel approach to the difficult intubation using a
      Glidescope in the awake spontaneously breathing patient. METHODS: In a difficult
      airway, the same approach for an awake fiberoptic intubation including excellent
      nerve blocks and sedation can be used with a Glidescope in the same fashion as a
      fiberoptic bronchoscope. RESULTS: The skill level for the awake Glidescope
      appears to be less, making it a useful tool for emergency room physicians and
      critical care physicians when used for awake intubation. It is particularly
      useful for the patient who fails the airway exam and also has macroglossia.
      CONCLUSION: This case report confirms that while not applicable to every patient,
      the awake Glidescope intubation does add to the previous existing armamentarium
      in this clinically challenging situation.

PMID- 20803869
TI  - Cholesterol crystal embolization in a Saudi patient after cardiac surgery--a case
      report.
AB  - An eroded atheromatous aorta may be a source of cholesterol crystal
      embolism(CCE). Embolization of atheromatous material accounts for obstruction of
      distal arterioles around which a foreign-body giant cell granuloma inflammatory
      reaction develops. The diagnosis is often delayed or un recognized because of
      varying or misleading clinical signs, such as renal insufficiency, digestive or
      neurological symptoms, or both or unexplained multiple-system disease. Although
      CCE can occur spontaneously, it has been increasingly recognized as an iatrogenic
      complication from an invasive vascular procedure, such as manipulation of the
      aorta during angiography or vascular surgery. It has also been reported to occur
      following anticoagulant therapy or thrombolysis. Patients undergoing coronary
      artery bypass grafting (CABG) often experience a combination of these factors:
      anticoagulation, intra-arterial angiographic procedures and intraoperative aortic
      cross-clamping. These multiple factors could account for the acute and severe
      postoperative clinical and biological findings observed in the case reported
      here. A 65-year-old Saudi man was admitted to our hospital on July 9, 2008 due to
      chest pain at rest. He had suffered from type 2 diabetes mellitus on Oral
      hypoglycemics, hypertension on treatment, impaired renal functions and
      hypercholesterolemia, he was an ex-smoker with history of diagnosed pulmonary
      interstitial fibrosis. He had Coronary angiography in another hospital on May
      2008 showing a left main lesion 60%, Left anterior descending lesion 90%,
      circumflex lesion 80% and Right coronary lesion 70%, three weeks later an acute
      on top of chronic deterioration in renal chemistry was observed for which
      conservative treatment was chosen.

PMID- 20803870
TI  - A case of unilateral Horner's syndrome diagnosed in retrospect following epidural
      analgesia during labour and caesarean section.
AB  - Horner's syndrome is a rare complication of epidural analgesia in labour.
      Although it is a sign of high sympathetic block, patients are usually
      haemodynamicaly stable. We report a case of undiagnosed Horner's syndrome
      complicating epidural analgesia in labour, where a standard dose of local
      anaesthetic was given for an emergency caesarean section without problems. This
      may confirm the benign nature of the syndrome.

PMID- 20803871
TI  - Successful resuscitation of an obstetric patient with suspected amniotic fluid
      embolism--case report.

PMID- 20803872
TI  - Neurological deficit following combined spinal-epidural anesthesia for knee
      arthroplasty.
AB  - A healthy man developed cauda equina syndrome after uneventful combined spinal
      and epidural anesthesia. No pre-existing neurologic disorder was recorded. There
      was no pain or paresthesia during needle placement, drug injection or catheter
      insertion. The sensory levels were improved within a few days following the
      deficit but little improvement on motor power but not on sphincter tone. Local
      anesthesia neurotoxicity was thought to be the leading cause of neurologic
      deficit in our case.

PMID- 20803873
TI  - A novel technique for oral and nasal tracheal intubation using the video assisted
      laryngoscopes (the GlideScope) in patients with difficult, and normal airways.

PMID- 20803874
TI  - Prolonged axillary block with levobupivacaine in an uremic patient.

PMID- 20803875
TI  - Antisemitism and the history of myasthenia gravis.

PMID- 20803876
TI  - Computed tomography study of the effect of orlistat on visceral adipose tissue
      volume in obese subjects.
AB  - BACKGROUND: Obesity has become a major public health problem worldwide.
      OBJECTIVES: To examine the effect of orlistat in promoting weight loss and its
      specific effect on visceral adipose tissue and subcutaneous adipose tissue as
      evaluated by computed tomography. METHODS: A prospective case series study of 10
      obese subjects was conducted. The 6 women and 4 men, age 50-67 years (mean 59 +/-
      8 years), had a mean body mass index of 34.1 +/- 3.2 kg/m2. All subjects were
      prescribed a mildly hypocaloric diet (600 kcal/day deficit). In addition, all
      subjects were treated with orlistat 120 mg 3 times a day for 20.1 +/- 7 weeks.
      RESULTS: The subjects had lost approximately 8.2 kg each, or 8.4% of their
      initial body weight. Mean body weight decreased from 98 +/- 13 to 89.8 +/- 13.6
      kg at the last followup visit (P = 0.0001); mean BMI decreased from 34.1 +/- 3.2
      to 30.3 +/- 3.9 kg/m2 (P = 0.0001), and mean waist circumference from 113.8 +/-
      11.4 to 107.6 +/- 10 cm (P = 0.0006). Mean total abdominal adipose tissue volume,
      evaluated by computed tomography, decreased from 426 +/- 104.3 to 369.8 +/- 99.6
      mm3 (P = 0.0001). Mean abdominal SAT volume decreased from 251.1 +/- 78.8 to 224
      +/- 81.1 mm3 (P = 0.006), and mean abdominal VAT volume decreased from 176 +/-
      76.7 to 141.6 +/- 67 mm3 (P = 0.0001). Thus, the total abdominal adipose tissue
      volume for the whole group decreased by 15.4%, and most of this decrease was
      attributable to the reduction in VAT (24.8%) as opposed to SAT (only 12%
      reduction) (P = 0.03). The weight reduction that occurred during the study was
      accompanied by a statistically significant reduction in levels of total
      cholesterol, low density lipoprotein-cholesterol, triglycerides, and fasting
      blood glucose. CONCLUSIONS: Our results demonstrate the effect of orlistat in
      reducing human visceral adipose tissue as evaluated by CT. The benefit of the
      treatment is further supported by the statistically significant reduction in
      cardiovascular risk factors.

PMID- 20803877
TI  - Breast asymmetry during adolescence: physiologic and non-physiologic causes.
AB  - BACKGROUND: Pathologic breast conditions are rare in childhood and adolescence.
      The spectrum of breast disease in the pediatric age group is different from that
      in adults, and most lesions are benign. OBJECTIVES: To describe the causes and
      characteristics of breast asymmetry in adolescents with normal endocrine profiles
      and sexual development. METHODS: The files of patients with a diagnosis of breast
      asymmetry referred to a tertiary pediatric center from 1990 to 2007 were reviewed
      for history and findings on physical examination with or without imaging,
      treatment and outcome. RESULTS: Eleven patients aged 12.5 to 18 years were
      identified. The cause of the breast asymmetry was traced to unpreventable medical
      factors in eight patients (physiologic, Poland anomaly, scleroderma),
      preventable/iatrogenic factors in two patients (chest tissue biopsy, thoracic
      drain), and possible combined medical-iatrogenic factors in one patient
      (scoliosis treated with a body brace). All patients were referred for breast
      reconstruction after full breast development. CONCLUSIONS: Severe breast
      asymmetry in adolescence may be due to congenital factors, diseases involving the
      breast tissue, or to the effects of medical treatment, and may have severe
      adverse psychological and social implications. To prevent iatrogenic breast
      asymmetry, physicians should be made aware of the sensitivity of the breast
      tissue and should avoid unnecessary tests/procedures that involve the chest wall.
      In most cases a precise medical history and physical examination can
      differentiate between physiologic and non-physiologic causes.

PMID- 20803878
TI  - Intraoperative parathormone measurements and postoperative hypocalcemia.
AB  - BACKGROUND: Hypocalcemia following thyroid and parathyroid surgery is a well
      recognized potential complication. OBJECTIVES: To determine the utility of
      intraoperative quick parathormone assay in predicting severe hypocalcemia
      development following parathyroidectomy for a single-gland adenoma causing
      primary hyperparathyroidism. METHODS: A retrospective cohort study was performed.
      IO-QPTH values were measured at time 0 (T0) before incision, and 10 (T10) and 30
      minutes (T30) following excision of the hyperfunctioning gland. Percent decrease
      in IO-QPTH at 10 minutes (T10), maximum percent decrease of IO-QPTH value, and
      lowest actual IO-QPTH value obtained at surgery were used to determine any
      correlation with the development of postoperative hypocalcemia requiring
      treatment. RESULTS: Percent decrease in IO-QPTH at 10 minutes, maximum percent
      decrease in IO-QPTH and lowest IO-QPTH value did not correlate with the lowest
      postoperative calcium levels measured 18 hours after surgery (r = 0.017, P =
      0.860; r = 0.018, P = 0.850; and r = 0.002, P= 0.985 respectively). For the
      purposes of our analysis, patients were subdivided into three groups. Group 1
      comprised 68 patients with normal calcium levels (serum Ca 8.6-10.3 mg/dl), group
      2 had 28 patients with hypocalcemia (8.1-8.6 mg/dl), and group 3 included 12
      patients with severe hypocalcemia (calcium level < or = 8.0 mg/dl) requiring
      calcium supplementation due to symptoms of hypocalcemia. There was no difference
      between the three groups in the lowest IO-QPTH value (P = 0.378), percent
      decrease in IO-QPTH (P = 0.305) and maximum percent dercrease in IO-QPTH (P =
      0.142). CONCLUSIONS: IO-QPTH evaluation was not useful in predicting the group of
      patients susceptible to develop severe postoperative hypocalcemia.

PMID- 20803879
TI  - Impact of myocardial blush on left ventricular remodeling after first anterior
      myocardial infarction treated successfully with primary coronary intervention.
AB  - BACKGROUND: Myocardial blush grade is a useful marker of microvascular
      reperfusion that may influence left ventricular dilation. OBJECTIVES: To assess
      the impact of MB grade on LV remodeling in patients undergoing successful primary
      PCI for first anterior ST elevation myocardial infarction. METHODS: In 26
      consecutive patients MB grade was evaluated immediately after primary PCI. Each
      patient underwent transthoracic echocardiography at 24 hours and 6 months after
      PCI for evaluation of LV volumes. LV remodeling was defined as an increase in end
      diastolic volume by > or = 20%. RESULTS: The presence of myocardial reperfusion
      (MB 2-3) after primary PCI was associated with a significantly lower rate of
      remodeling than the absence of myocardial reperfusion (MB 0-1) (17.6% vs. 66.6%,
      P = 0.012). Accordingly, at 6 months, patients with MB 2-3 had significantly
      smaller LV end-diastolic volume (94 +/- 21.5 vs. 115.2 +/- 26 ml) compared with
      patients with MB 0-1. In univariate analysis, only MB (0-1 versus 2-3) was
      associated with increased risk of LV remodeling (odds ratio 9.3, 95% confidence
      interval 1.45-60.21, P = 0.019). CONCLUSIONS: Impaired microvascular reperfusion,
      as assessed by MB 0-1, may be associated with LV remodeling in patients with
      STEMI treated successfully with primary PCI.

PMID- 20803880
TI  - Falls in stroke patients: risk factors and risk management.
AB  - BACKGROUND: Falls are common events among hospital inpatients and constitute a
      major health problem in the rehabilitation setting. Many risk factors for falls
      have been identified for stroke patients, such as muscle weakness, medication
      side effects, hypoglycemia, hypotension, etc. OBJECTIVES: To assess the risk
      factors for falls among patients hospitalized for rehabilitation following acute
      stroke. METHODS: In a retrospective study of 56 falls over a period of 5 years in
      41 stroke patients hospitalized for rehabilitation we surveyed the nurses' safety
      risk assessment of the fall. Thirty patients fell once, 9 patients twice and 2
      patients four times. The data were obtained from the medical and nursing records.
      Safety precautions were taken by the nurses for the entire group of patients.
      RESULTS: Most of the falls occurred among male patients who had reduced muscular
      tone (70%), paralysis (54%) and/ or hypoesthesia in the involved side of the
      body. Patients who suffered from hemiplegia fell more often than those with
      hemiparesis (Wilcoxon rank sum test, P = 0.04, one-sided). Forty-eight percent of
      the falls occurred during the first month after the last stroke, 70% during the
      morning or the afternoon, and 62% occurred close to the patient's bed. In 89% of
      falls the patients used hypoglycemic, antihypertensive, tranquilizing or
      neuroleptic drugs. Communication disorders (29%), hemianopia or blindness (21%)
      and visuospatial agnosia (18%) were incremental risk factors for falls. Fifty
      percent of the falls were caused by either an intrinsic or extrinsic mechanism.
      CONCLUSIONS: These data suggest that the group of stroke patients at risk for
      falls in a rehabilitation department can be identified by a variety of impairment
      and functional assessments. The information may be potentially useful for
      designing interventions directed at reducing fall frequency among stroke
      survivors.

PMID- 20803881
TI  - Yield of recommended blood tests for neonates requiring phototherapy for
      hyperbilirubinemia.
AB  - BACKGROUND: Hyperbilirubinemia of the newborn is common. Rarely is an underlying
      disease other than physiologic hyperbilirubinemia considered the cause of high
      bilirubin levels. Some of the laboratory tests recommended by the American
      Academy of Pediatrics are expensive and do not always lead to diagnosis.
      OBJECTIVE: To evaluate the efficacy of standard laboratory tests performed on
      newborn infants requiring phototherapy for hyperbilirubinaemia. METHODS: We
      conducted a retrospective chart review that included neonates born during a 6
      month period with birth weight 2500 g treated with phototherapy for
      hyperbilirubinemia (n = 282) according to published guidelines. The main outcome
      measures were primary and maximal bilirubin values (mg/dl), time to jaundice (in
      days), the number of bilirubin tests undertaken and whether the patient showed
      abnormal functioning, and the number of days in follow-up. RESULTS: Thirty-three
      neonates (11.7%) were positive in at least one laboratory test (defined as
      "Abnormal" in our study), 45.5% of whom met the criteria for phototherapy during
      the first 48 hours of life. Among the newborns who were negative for all
      laboratory tests (defined as "Normal"), only 6.8% met phototherapy criteria
      within their first 48 hours of life (P < 0.001). In the Normal group there was a
      consistent decrease in total serum bilirubin values shortly after phototherapy
      was begun, while the Abnormal group presented an increase in serum bilirubin
      values during the first 12 hours of phototherapy. None of the infants had
      conjugated (direct) hyperbilirubinemia during the study period. CONCLUSIONS: Most
      neonates presenting with a laboratory identifiable etiology for
      hyperbilirubinemia (i.e., hemolysis) can be distinguished from those who test
      negative, mainly based on the timing of presentation and response to
      phototherapy. A more meticulous selection of patients and reduction in the
      magnitude of routine laboratory testing can safely reduce discomfort to infants
      with hyperbilirubinemia as well as costs.

PMID- 20803882
TI  - Penicillin and ceftriaxone susceptibility of Streptococcus pneumoniae isolated
      from cerebrospinal fluid of children with meningitis hospitalized in a tertiary
      hospital in Israel.
AB  - BACKGROUND: Streptococcus pneumoniae is now the predominant pathogen causing
      meningitis. The resistance of S. pneumoniae to penicillin and third-generation
      cephalosporins has grown steadily. OBJECTIVES: To assess the antibiotic
      susceptibility of S. pneumoniae isolated from the cerebrospinal fluid of children
      with meningitis, and determine the antibiotic regimen appropriate for suspected
      bacterial meningitis in Israel. METHODS: The study group included 31 children
      with 35 episodes of meningitis hospitalized from 1998 to 2006. S. pneumoniae
      isolates from the cerebrospinal fluid were tested for susceptibility to
      penicillin and ceftriaxone. RESULTS: Of the 35 isolates, 17 (48.6%) showed
      resistance to penicillin (minimum inhibitory concentration > or = 0.12
      microg/ml). Only 3 isolates (8.6%) showed intermediate resistance to ceftriaxone
      (> or = 0.5 and < (2 microg/ml), and none showed complete resistance (MIC > or =
      2 microg/ml). The rates of antibiotic resistance were higher in children who were
      treated with antibiotics prior to admission (penicillin 88.9% vs. 34.6%, P =
      0.007; ceftriaxone 22.2% vs. 3.8%, P = 0.156). CONCLUSIONS: The rate of
      penicillin resistance is high in children with S. pneumoniae meningitis in
      Israel, especially in those treated with oral antibiotics prior to admission.
      Resistance to ceftriaxone is infrequent though not negligible. On the basis of
      these findings, current recommendations to empirically treat all children with
      suspected bacterial meningitis with ceftriaxone in addition to vancomycin until
      the bacterial susceptibility results become available are justified also in
      Israel.

PMID- 20803883
TI  - Antisemitism and the history of medicine: the challenge then and now.

PMID- 20803884
TI  - It's not only the overweight: it's the visceral fat.

PMID- 20803885
TI  - Addiction, impulsivity and obsessive-compulsive disorder: new formulation
      revealing ancient wisdom.

PMID- 20803886
TI  - Ondine's curse--never too late.

PMID- 20803887
TI  - Asymptomatic carotid stenosis: natural history versus therapy.

PMID- 20803888
TI  - Pathological gambling: an impulse control disorder? Measurement of impulsivity
      using neurocognitive tests.
AB  - Pathological gambling is classified in the DSM-IV-TR (Diagnostic and Statistical
      Manual of Mental Disorders) and in the ICD-10 (International Classification of
      Disease) as an impulse control disorder. The association between impulsivity and
      pathological gambling remains a matter of debate: some researchers find high
      levels of impulsivity within pathological gamblers, others report no difference
      compared to controls, and yet others even suggest that it is lower. In this
      review we examine the relationship between pathological gambling and impulsivity
      assessed by various neurocognitive tests. These tests--the Stroop task, the Stop
      Signal Task, the Matching Familiar Figures Task, the Iowa Gambling Task, the
      Wisconsin Card Sorting Test, the Tower of London test, and the Continuous
      Performance Test--demonstrated less impulsivity in gambling behavior. The
      differences in performance between pathological gamblers and healthy controls on
      the neurocognitive tasks could be due to addictive behavior features rather than
      impulsive behavior.

PMID- 20803889
TI  - Late-onset central hypoventilation presenting as extubation failure.

PMID- 20803890
TI  - Non-traumatic epitympanic cerebrospinal fluid leakage presenting as recurrent
      bacterial meningitis.

PMID- 20803891
TI  - Madelung's disease.

PMID- 20803892
TI  - Leukemoid reaction in lung cancer patients.

PMID- 20803893
TI  - [Toxicological evaluation of crop protection chemicals in the EU registration
      process].
AB  - Authorisation of crop protection chemicals prior to placing into the market is
      being regulated with standardized regulations in the European Community
      territory. The Member States are obliged to introduce all provisions constituting
      the base for the evaluation of protection chemicals and determining their safety
      for man and environment. The rules governing toxicological evaluation of plant
      protection products and their active substances have been discussed and the
      practical relevance of the harmonized provisions for the safety assessment of
      pesticides in the EU were also presented. Introducing the assessment of risk
      resulting from treatments with chemical crop protection chemicals in the
      registration process widens the safety margin for users of plant protection
      products as well as fixes new safety standards at agrochemical works.

PMID- 20803894
TI  - [Benzene in food and human environment].
AB  - Benzene is releasing to environment in cause of industry activities. This
      compound is known as carcinogenic. This article contains information about
      benzene occurrence in people environment and sources of people exposition on this
      compound. Toxicology and metabolism in human organism were discussed. Benzene
      contamination of various food was presented on the basis of our results and also
      other European and American investigations and Codex Alimentarius documents.
      Especially formation and occurrence of benzene in non-alcoholic beverages
      preserved by benzoates were considered. Article describes also action, which was
      taken up by non-alcoholic beverages industry to mitigate benzene formation in
      soft drinks. National regulations concerning maximum levels of benzene in
      drinking water and air were also presented.

PMID- 20803895
TI  - [The effects of di-n-butyl phthalate on the somatic cells of laboratory mice].
AB  - Phthalates are widely used as a plasticizers in manufacture of synthetic
      materials and as solvents in sanitary products, cosmetics and pharmaceutical
      products. Dibutylphthalate (DBP) is used as a plasticizers and as a textile
      lubricating agent and as solvent in printing ink. The study aimed the evaluation
      of the magnitude of DNA damage in liver and bone marrow cells and estimation of
      dibutyl phthalate (DBP) concentration in peripheral blood following prolonged
      exposure to DBP. Experiments were conducted an the Pzh:Sfis male mice. Animals
      were exposed 8 weeks, 3 days per week per os to DBP suspension in oil in doses of
      500 mg/kg bw (1/16 LD50) and 2000 mg/kg bw (1/4 LD50). Following groups of mice
      were sacrificed 4 and 8 weeks after the start of exposure and 4 weeks after the
      end of exposure. Decreased body weight of mice and statistically significant
      decreased liver and relative liver weights were observed following 8-weeks
      exposure to 2000 mg/kg bw DBP. In the same time higher however not statistically
      significant level of DNA damage measured by Comet assay in liver cells were
      noted. DBP did not induce enhanced frequency of DNA damage in bone marrow cells.
      Following 8-weeks exposure to the dose of 2000 mg/kg bw DBP the increased level
      of DBP in peripheral blood was observed. Enhanced levels of DBP were still noted
      4 weeks after the termination of exposure. Results confirmed that DBP acts as a
      weak mutagen for DNA of somatic cells. However, following prolonged exposure this
      compound seems to undergo slower metabolism and was reaching temporarily higher
      levels in peripheral blood.

PMID- 20803896
TI  - [Retinyl palmitate and oxidative stress reduction in rats].
AB  - The effect of retinyl palmitate dose on oxidative stress reduction induced by
      physical activity was the aim of study. The experiment was carried out on Wistar
      strain males rats, which were trained by running on trademill with speed 20
      m/min. during 10 days. The rats were administered with 7, 5, 15 or 60 microg of
      retinyl palmitate daily to each one. The level of retinol, lipid peroxides,
      antioxidant potential in serum and retinyl esters in liver were measured. It was
      shown that retinyl palmitate reduced oxidative stress, independently to its daily
      dose.

PMID- 20803897
TI  - [Monitoring of contamination of foodstuffs with elements noxious to human health.
      Part II. Mineral waters, soft drinks, fruits, nuts, rice, soybeans, fish and
      seafood].
AB  - Results of the 5-years cycle (2004-2008) monitoring investigations on food
      contamination with elements noxious to human health, involving testing of mineral
      waters and soft drinks (226 samples), fruits (467 samples), rice (234 samples),
      soybeans (236 samples), nuts and peanuts (237 samples), fish and seafood (237
      samples) are discussed. The parties involved in testing were: laboratories of
      State Sanitary Inspection and the national reference laboratory of the Department
      of Food and Consumer Articles Research of National Institute of Public Health -
      National Institute of Hygiene. The reported metals contents did not give rise to
      health concerns, remaining generally below the levels set forth in food
      legislation and being comparable with contamination levels reported in other
      European countries; and for cadmium--often lower. Health hazard assessment was
      performed taking into account the mean contamination levels obtained and average
      domestic consumption of these food products groups in Poland. The highest intake
      expressed as the percentage of provisional tolerable weekly intake (PTWI) was
      obtained for mercury in fish, which has reached mean 3.2% PTWI. Controlled fish
      consumption recommendations should be adhered to by prospective mothers, pregnant
      women, breast-feeding women and young children. Lead and arsenic intake with
      mineral waters and soft drinks comprises approx. 15% of total intake of these
      elements with food.

PMID- 20803899
TI  - [Evaluation of microbiological quality of seasoning purchased in the retail
      network].
AB  - The estimation of microbiological quality of seasoning purchased in the retail
      network was the aim of this work. The study included five kinds of seasoning
      manufactured by four Polish companies. Microbiological analysis of the material
      included: total count of mesophilic aerobic bacteria and their spores, count of
      yeast and moulds and occurrence of coliforms bacteria, E. coli, Salmonella sp.
      and S. aureus. The results showed that the total count of mesophilic aerobic
      bacteria was high (10(5) -10(6) cfu x g(-1)) in the most of estimated spices and
      bacteria occurred mainly as spores. The low titre of coliform reduced down to 10(
      2)-10(-3), occurrence of E. coli it was stated in 20% of samples of spices.
      However no pathogenic bacteria (Salmonella sp., S. aureus) was detected.
      Contamination of seasoning by yeasts and moulds was low in majority of samples
      and only in two samples the count of moulds was higher than 10(3) cfu x g(-1) and
      not answered requirements. Moulds were mainly represented by Aspergillus sp. (A.
      glaucus, A. niger, A. flavus) and than by Penicillium sp. and Rhizopus sp.
      Microbiological quality of seasoning was differentiated in dependence on the
      manufacturer.

PMID- 20803898
TI  - [Characteristics of bottled waters available for purchase in the Silesia region].
AB  - The aim of the study was to characterize bottled waters available for purchase in
      the Silesia region in relation to total mineral contents and main ion
      concentrations. In descriptive epidemiological design, we investigated 70 types
      of available for purchase bottled waters (mineral, spring and table ones), sold
      in glass or PET bottles. On the basis of data revealed by producers, we analyzed
      total mineral contents and concentrations of main cations (sodium, magnesium,
      calcium and potassium) and anions (hydrocarbons, sulfate, chloride and fluoride).
      The study group comprised of 35 mineral waters and 35 spring waters. There were
      no table waters available for purchase. Total mineral content in mineral waters
      was 1310.0 +/- 814.8 mg/dm3, concentration of cations was 295.4 +/- 181.2 mg/dm3
      and of anions: 968.1 +/- 638.5 mg/dm3. The concentrations of investigated cations
      were adequately: Ca 178.7 +/- 107.3 mg/dm3, Mg 54.3 +/- 52.7 mg/dm3, Na 53.5 +/-
      67.4 mg/dm3 and K 8.9 +/- 9.4 mg/dm3. The contents of anions were: HCO3 930.5 +/-
      647.2 mg/dm3, SO4 25.9 +/- 21.6 mg/dm3, Cl 11.5 +/- 11.2 mg/dm3 and F 0.2 +/-
      0.27 mg/dm3. In relation to spring waters, total mineral content was 365.9 +/-
      150.8 mg/dm3 and concentrations of cations and anions were adequately: 87.9 +/-
      37.6 mg/dm3 and 255.1 +/- 111.9 mg/dm3. The concentrations of analyzed cations
      were adequately: Ca 55.4 +/- 19.7 mg/dm3, Mg 10.6 +/- 6.9 mg/dm3, Na 20.6 +/-
      30.3 mg/dm3 and K 1.3 +/- 1.7 mg/dm3. For anions the concentrations were as
      follows: HCO3 223.2 +/- 105.8 mg/dm3, SO4 18.9 +/- 19.1 mg/dm3, Cl 12.9 +/- 16.5
      mg/dm3 and F 0.11 +/- 0.12 mg/dm3. The quantity of available for purchase mineral
      waters is similar to spring waters. Total mineral content is on average 4-fold
      higher for mineral than spring waters. The variation of investigated ions
      concentrations is higher for mineral than spring waters. Both mineral and spring
      waters differ the most in relation to Na and K concentrations, and Cl and F
      contents.

PMID- 20803900
TI  - [Gluten content in special dietary use gluten-free products and other food
      products].
AB  - Gluten content of 22 special dietary use gluten-free products and 19 naturally
      gluten-free products was analysed by ELISA method. Gluten content in dietetic
      foods ranged from 5.19 to 57.16 mg/kg. Within the group of foods "gluten-free" by
      nature--gluten was not detected in rice and buckwheat groats samples, however in
      rice flakes and pearl millet gluten content ranged from 7.05 mg/kg- 27.51 mg/kg.
      Particularly high contamination with gluten (> 100 mg/kg) was detected in oat
      products what puts in doubt their usefulness in gluten-free diet.

PMID- 20803901
TI  - [Determinants of lutein intake in the selected group of adolescents].
AB  - The aim of this work was evaluation of lutein intake in group of 110 adolescents
      from big city (Warsaw) and little town (Ilza). The group consisted of 56 girls
      and 54 boys, high school attending persons, aged 16 - 20. The study was carried
      in the spring of 2007, with the use of three-days dietary food records method.
      The mean intake of lutein was 1.87 mg/person/ day and it was dependent on
      respondents sex. Girls consumed 1.67 mg per day of lutein, while boys consumed
      2.07 mg per day. Index of BMI, place of dwelling, place of study, physical
      activity, mother occupation as well as amount of siblings did not have an impact
      on the intake of lutein. The main sources of lutein in adolescents food rations
      were vegetables (64%), including dark-green leafy vegetables (40%), eggs (12%)
      and cereal products (12%). Potatoes (5%), fruit (3%) and juices (3%) did not
      contribute significant amount to dietary intake of lutein.

PMID- 20803902
TI  - [Selected lifestyle and health condition indices of adults with varied models of
      eating].
AB  - The aim of this research was to analyse certain lifestyle parameters and health
      condition indices among people with traditional and vegetarian models of eating.
      The research conducted shows that vegetarians present a higher level of caring
      about their health, which is expressed on a scale of pro-health behaviours, than
      people with traditional model of eating. A higher percentage of them take up
      physical activity in their free time (80% vs. 70%), additionally, they more
      seldom drink alcohol and smoke cigarettes. Alcohol abstinence is declared by 75%
      of vegans, 25% of lacto-ovo vegetarians and only 8% of people with traditional
      model of eating. Tobacco non-smoking is declared by 94% of vegans, 74% of lacto
      ovo vegetarians and 67% of traditional eating people. It has also been shown that
      some psychosomatic health indices, especially concerning digestive duct/system,
      remain varied in regard to the model of eating followed. The research has proven
      that vegetarian model of eating influences other--non-eating--pro-health
      behaviours and in this way it shapes healthy lifestyle of research subjects.

PMID- 20803903
TI  - [Nutritional habits in children and adolescents practicing fencing. Part II.
      Characteristics of eating between meals].
AB  - The aim of this study was to assess the longest interval between meals, eating
      until the feeling of satiety and eating between meals in children and adolescents
      who attended sports schools. The questionnaires on were filled in by 141 children
      and adolescents who practised fencing and attended sports classes in primary and
      secondary schools. The days with training and the days free of training were
      analysed separately. The influence of gender and age on the longest interval
      between meals, eating until the feeling of satiety and eating between meals on
      the days with training and the days free of training was analysed by means of the
      SPSS 12.0 PL for Windows computer programme. Gender and age had statistically
      significant influence on the longest interval between meals, eating until the
      feeling of satiety and eating vegetables, cured meat, sweets and energy drinks
      between meals. Eating between main meals was prevalent in the studied population.
      Higher percentage of girls ate fruit and vegetables between main meals, while
      higher percentage of boys ate sandwiches, irrespectively of the type of the day-
      with training or free of training.

PMID- 20803904
TI  - [Eating habits of obese patients with diagnosed hypertension].
AB  - The study was aimed, therefore, at investigating eating habits of patients with
      diagnosed arterial hypertension of the Clinic of Occupational Diseases and
      Arterial Hypertension, Clinical Hospital of the Medical Academy in Wroclaw. It
      covered 52 persons with diagnosed arterial hypertension--patients of the Clinic
      of Occupational Diseases and Arterial Hypertension, Clinical Hospital of the
      Medical Academy in Wroclaw. Evaluation of their eating habits was conducted with
      the use of an original, standardized questionnaire elaborated at the Chair of
      Human Nutrition, Wroclaw University of Environmental and Life Sciences. Amongst
      examined patients 12.9% of men and 33.3% of women were eating 4 meals, 5 meals-
      5% of women and 3% of men, and more than 5 meals--3.2% of men. It was
      demonstrated that the majority of sick persons have eaten the white wheat bread.
      It concerned over 33% women and 58% men. Close 29% patients vegetables were found
      in a diet in 3 portions, at 14% of them--in 4 portions, however almost 10% ill
      women ate 5 portions of vegetables mane. About 38% women provided with only 2
      portions of vegetables per day, and 10%--only one. The appropriate supply of
      fruits realized 81% of women and 78% of men. Irregular consumptions of the milk
      and dairy products declared 67% women and 48% men. It is recommended the
      alteration of the warehouse of the nutritional rations ill from the arterial
      hypertension consists for increasing cereals in the diet of the participation of
      solid meal, leguminous seeds, vegetables and fruits and reducing the share of
      animal fats.

PMID- 20803905
TI  - [Selected nourishment habits depending on physical activity of 14-16 year-old
      teenagers in the north-eastern Poland on the example of Sokolski district].
AB  - The aim of the survey was the evaluation of specific nourishment habits among 14
      16 year-old teenagers of a different physical activity in the north-eastern
      Poland on the example of Sokolski district. The 14-16-year teenagers from
      secondary school, in Sokolski district (368 boys and 368 girls) were examined.
      They were chosen at random. The researches were carried out from November to
      December in 2006-2007 school year by the method of a diagnostic poll with the aid
      of the anonymous questionnaire. The low percentage of teenagers who declared the
      proper nourishment habits was stated, and it was observed that the more
      physically active teenagers were the more of them declared rational nourishment
      habits within the scope of analyzed nourishment habits.

PMID- 20803906
TI  - [Physical activity as an additional way of rehabilitation of type 2 diabetes
      sufferers].
AB  - The aim of the study was to evaluate physical activity and resting manners of
      type 2 diabetes sufferers. The research was conducted in health care centres in
      Malopolskie voivodship in 2008. 100 people (66 women, 34 men) aged between 40 and
      84 filled in anonymous questionnaires. The majority of the respondents rested
      passively, half of the surveyed indicating lying, watching TV and listening to
      music as a way of resting. The majority of the ill did not embark upon physical
      activity as an essential element in treating diabetes. The most frequently
      (systematically) practised forms of physical activity were animal breeding,
      gardening and strolling. Poor health condition discouraged the surveyed from
      undertaking physical activity.

PMID- 20803907
TI  - [The examination of content and structure of humic compounds in Miocene water,
      therapeutic peats and lignite on the basis of differential absorbing spectra].
AB  - In the examination the differential absorbing spectra of humic compounds present
      in underground Miocene waters were compared with the spectra originated from
      therapeutic peat and lignite. From the samples of examined material trough
      selective extraction were separated humic acids, hymatomelanic acids and fulvonic
      acids. The spectrograms in the range UV-VIS of those compounds were made. The
      results of the fourth degree differential were spectra were with well separated
      peaks for specified wave-length. In spectra obtained from Miocene water and peats
      were found peaks characteristic for specific frequently common electromagnetic
      radiation wave-length. In spectra obtained from lignite there were not found
      peaks characteristic for humic acids.

PMID- 20803908
TI  - [Microbiological quality of indoor air in dentist's offices].
AB  - It's a well-known fact that water-air aerosol can be a result of some dentist's
      activity during regular dental surgery and can contain broad range of
      microorganisms from dental plaque, saliva and pus. Assessment of dentist's
      activity impact on bacteria concentration in air of dentist surgery was a main
      purpose of this assay. Presented data contains results of four total number of
      bacteria and fungi in air assays made with fifty minutes intervals. Air samples
      was taken in dentist's office during regular dental surgery of patients afflicted
      with oral cavity infection with pus. Due to defective ventilation system,
      bacteria's concentration in air samples increased from less than thousand cfu/m3
      to almost three thousands cfu/m3. Obtained results demonstrated that aerosol
      containing bacteria is released during regular dental surgery so the
      concentration of potentially infectious bacteria around patient and dentist can
      increase up to three thousands cfu/m3.

PMID- 20803909
TI  - Awareness regarding contraception and population control among school going
      adolescents.
AB  - Growing sexuality among adolescents increases their risk of getting reproductive
      tract infections and pregnancy. This Cross sectional survey was done to assess
      the knowledge and attitude of higher secondary school children regarding
      contraception and population control. Majority of students (94.4%) were aware of
      contraceptives and their easy availability on chemist shop. However very few were
      aware of name and how to use them and 60% of them considered that condom is an
      emergency contraceptive. Lack of employment facilities as a consequence of
      uncontrolled population growth was the main concern of both boys and girls. The
      two children norm was acceptable to most, with one son and one daughter. All
      perceived that there is need to be informed about contraceptives. Most of the
      adolescents are misinformed about contraceptives and their attitude is not
      favorable as far as responsibility is concerned. There is an unmet need of
      contraceptive & population control knowledge and attitude among school
      adolescents and require urgent intervention.

PMID- 20803910
TI  - An assessment of accuracy of mothers' presumptive diagnosis of fever at home in
      southwest Nigeria: evidence for switch to parasite-based diagnostic test.
AB  - OBJECTIVE: Home management of malaria (HMM) strategy was based on presumptive
      diagnosis of malaria and use of correct dose of chloroquine. However, the
      development of chloroquine resistant parasites in most endemic areas necessitated
      the recommendation of artemisinin combination therapy (ACT); and this has been
      demonstrated to be effective in HMM. However, the recommendation that ACT should
      be dispensed only to laboratory confirmed cases underscores the need to review
      the accuracy of mothers' presumptive diagnosis and provide evidence for a switch
      to parasite based diagnostic test. METHODS: This was a follow-up study nested to
      a larger controlled intervention study carried out to assess the effect of
      malaria treatment guideline on mothers' adherence to correct treatment of malaria
      in children. In a subset, thick blood smears were prepared from finger prick
      blood samples of febrile children who have been presumptively diagnosed to have
      malaria by mothers on Days 0, 1, 2, 3, 7 and 14 to detect parasitaemia. The
      presumed diagnosis was compared with the presence of parasitaemia. RESULTS: A
      total of 162 children with febrile illness (88 and 74 in intervention and control
      groups respectively) were studied. Sixty-four (72.7%) and 62 (83.8%) of the
      febrile cases presumed to have malaria in the intervention and control groups
      respectively had parasitaemia on Day 0. The sensitivity and specificity of
      mothers' diagnoses was 78.1% and 29.2%; 82.3% and 8.3%; in the intervention and
      control groups respectively. CONCLUSION: The low specificity of presumptive
      diagnosis has implication for the deployment of ACT at the community level in
      Nigeria. This supports current views on the need for a more sensitive and
      specific parasite-based diagnosis of malaria before ACT treatment. Further study
      to compare presumptive diagnosis of malaria with malaria diagnostic test carried
      out at the community level is needed to inform policy on the adoption of parasite
      based malaria diagnosis at community level.

PMID- 20803911
TI  - Suspected outbreak of cutaneous anthrax in Kasese district, the investigation and
      response, April to May 2007.
AB  - BACKGROUND: A report of suspected anthrax was submitted by the Kasese District
      Health Office to the Epidemiology Surveillance Division of Ministry of Health. A
      joint team comprising officers from MOH, IPH and MPH officers proceeded to the
      district to investigate the reported threat of anthrax. The investigations were
      conducted in Bwera HSD, Bukonjo West County, in communities bordering Queen
      Elizabeth National Park. OBJECTIVES: The main objectives of the study were to
      verify the existence of anthrax and assess the risk factors for the suspected
      outbreak of anthrax in Kasese district. METHODS: The methods involved discussion
      with the DHT members; reviewing the surveillance data and hospital records, and
      reorienting the case definitions to the specific type of anthrax. In addition
      tracing the reported cases in the community in order to establish exposure to the
      risk factors and sensitize the community. RESULTS: Cutaneous anthrax was
      clinically diagnosed as the cause of the reported anthrax, both from the medical
      records and observation of cases found during the investigation. The index case
      was a 44 year old male, from Hurukungu village, Kyempara parish, a household with
      one wife and 4 children. This case skinned a goat that had died under mysterious
      circumstances and the meat was eaten with family members. Two other cases were
      members of the same family and the fourth case was from the same community and
      bought meat from the index case. All the four cases presented with a history of
      blister like lesions that eventually ulcerated with swelling of surrounding skin
      in different parts of the body. There were no other systemic symptoms reported in
      all the cases. All the suspected cases received antibiotics to which anthrax is
      sensitive. There were no laboratory investigations done by the time of the
      investigations since many of the cases identified were already on treatment and
      recovering from the infection, therefore no samples were taken from them. Review
      of records revealed that reporting of anthrax has continued since the year 2005
      with cases ranging from I to 4 from villages that shares a common boarder with
      Queen Elizabeth National Game Park. This particular outbreak was associated with
      eating of meat from a goat that had died of unknown cause. The health workers
      from the health units where cases were reported were found to have the basic
      knowledge and skills to suspect anthrax. However, they had no guidelines to help
      them identify cases of anthrax accurately. The available Standard Case Definition
      (SCD) booklets, IDSR Technical Guidelines, and laboratory SOPs have no
      information on anthrax. No samples have ever been removed from suspected cases
      for laboratory investigation. The health units have the appropriate antibiotics
      for treatment of suspected case. The Local Council Chairpersons, Veterinary
      extension workers, and the health educators have sensitized the community in the
      past against eating dead animals and that they should notify the authorities, and
      bury all dead animals immediately. However this hasn't yet been done for the
      current outbreak. CONCLUSION: The outbreak of anthrax in Bwera sub-county
      followed eating of meat from a goat which had died from unknown causes. Suspected
      cases have not been confirmed by laboratory but treated empirically with
      antibiotics. All new cases of suspected anthrax that report at the lower health
      units without laboratory facilities should be referred to hospital for
      investigation to confirm the diagnosis. There is need to include guidelines on
      anthrax in the SCD Booklets, laboratory SOPs and IDSR technical guidelines.
      Resensitization of the affected communities about the prevention of anthrax
      should be done immediately.

PMID- 20803912
TI  - The knowledge, attitude and practices of food handlers in food sanitation in a
      metropolis in south eastern Nigeria.
AB  - The spread of diseases through food is still a common problem which results in
      appreciable morbidity and occasional mortality. Food handlers play an important
      role in ensuring food safety throughout the chain of production, processing,
      storage and preparation. This study was designed to determine knowledge, attitude
      and practice of food handlers towards food-borne diseases and food safety. A
      total of 430 food handlers were randomly selected from Owerri Metropolis of Imo
      State Nigeria and interviewed using structured pretested questionnaire. Almost
      half (48.4%) of the respondents had poor knowledge of food sanitation. Multiple
      logistic regression showed type of premise [Odd Ratio (OR) = 4.0, 95% confidence
      interval (CI) = 1.8 - 7.5, P = 0.0004], educational level (OR = 0.4, 95% CI = 1.8
      -7.4, P = 0.0003) and job status of food handlers (OR = 0.5, 95%, CI = 0.3 - 0.8,
      P = 0.0031) significantly influenced the score level of knowledge. There was no
      significant difference in attitude and practice between trained and untrained
      food handlers. Findings of this study may be important in planning health
      education intervention programs for food handlers in order to improve their
      knowledge, attitude and practice towards food borne diseases and food safety.
      This will help in reducing morbidity and mortality due to food-borne diseases.

PMID- 20803913
TI  - Services and attitudes to people living with HIV/AIDS among college students in
      Dar-es-Salaam, Tanzania.
AB  - OBJECTIVES: The objective of this study was to evaluate acceptability of
      voluntary testing, counselling and treatment services and attitudes towards
      people living with HIV/AIDS from young people's point of view. METHODS:
      Qualitative study (face-to-face interviews in which tapes were used) were carried
      out in 20 interviewed college students aged between 19-24 years of both sexes
      based in Dar-es-Salaam, Tanzania. RESULTS: Results showed that voluntary
      counselling and testing services were limited in the study area at the time of
      study. Participants complained of unfriendly services and unco-operative staff,
      poor counselling services and shortage of facilities and staff. There was fear of
      HIV/AIDS related stigma toward people living with HIV and AIDS, thus fostering
      stigma and isolation against them. Results further demonstrate that HIV/AIDS
      related stigma is still a very serious problem in Tanzania. Lack of HIV/AIDS
      related knowledge and the life-threatening character of the disease were seen as
      the most important determinants of AIDS-related stigma. The main benefit to go
      for VCT was 'knowing your status before marriage', whereas main barriers for
      testing were 'fear of being stigmatised' and 'fear of knowing your HIV positive
      status'. CONCLUSION: The results suggest that there is need of VCT specific
      intervention programs for young people in colleges in Tanzania to emphasize of
      importance of VCT services and HIV/AIDS education program to educate students'
      understanding of people living with HIV/AIDS, thus reducing stigma towards people
      living with HIV/AIDS.

PMID- 20803914
TI  - Gender difference in HIV status disclosure among HIV positive service users.
AB  - OBJECTIVES: There exists a strong relationship between gender and HIV/AIDS, with
      gender inequalities contributing to HIV, and HIV/AIDS in turn worsening gender
      inequality. In Sub-Saharan Africa only few studies have examined gender
      differences in HIV status disclosure. Therefore this study explores gender
      differences in HIV-positive status disclosure. METHODS: A facility based cross
      sectional study using qualitative and quantitative data collection methods was
      conducted among 70 randomly selected HIV positive service users in South West
      Ethiopia. Data were collected using a pre-tested interviewer-administered
      structured questionnaire. Gender specific factors associated with disclosure to a
      main partner were analyzed using logistic regression. RESULTS: Among 705
      participants, an equal number of men and women (94.6% men vs. 94.3%, women, p =
      0.876) indicated that the have disclosed their result to at least one individual
      and the majority (90.9% men vs. 90.7% women, p = 0.906) disclosed their result to
      their current main partner. It is customary to tell my partner everything was the
      frequently cited motivator for disclosing (36.3% men vs. 44.6% women, p = 0.147).
      Reasons for non-disclosure varied by gender: men are more tender-hearted about
      their partners while women are more pragmatic. The individual contextual meaning
      of fear of partner reaction entirely differs between men and women. Men were
      concerned about their partner's worry and exposure of their own unfaithfulness.
      Women feared physical violence and social and economic pressure in raising their
      children. For men, disclosure of HIV results to a sexual partner was positively
      associated with knowing the partner's HIV status and discussion about HIV testing
      prior to seeking services, while for women it was associate with knowing the
      partner's HIV status, advanced disease stage,attending no more than primary
      education, being married, and perceiving the current relation as long-lasting.
      CONCLUSION: In this study there was no significant difference in the proportion
      of HIV status disclosure among men and women However, the contextual barriers and
      motivators of disclosure varied by gender. Therefore future interventions should
      consider the importance of socially constructed gender roles in the efforts to
      increase HIV status disclosure.

PMID- 20803915
TI  - Classification of mistakes in patient care in a Nigerian hospital.
AB  - Recent discussions on improving health outcomes in the hospital setting have
      emphasized the importance of classification of mistakes in health care
      institutions These discussions indicate that the existence of a shared
      classificatory scheme among members of the health team indicates that errors in
      patient care are recognised as significant events that require systematic action
      as opposed to defensive, one-dimensional behaviours within the health
      institution. In Nigeria discussions of errors in patient care are rare in the
      literature. Discussions of the classification of errors in patient care are even
      more rare. This study represents a first attempt to deal with this significant
      problem and examines whether and how mistakes in patient care are classified
      across five professional health groups in one of Nigeria's largest tertiary
      health care institutions. The study shows that there are wide variations within
      and between professional health groups in the classification of errors in patient
      care. The implications of the absence of a classificatory scheme for errors in
      patient care for service improvement and organisational learning in the hospital
      environment are discussed.

PMID- 20803916
TI  - The effectiveness of a syndromic approach in managing vaginal infections among
      pregnant women in northern Tanzania.
AB  - OBJECTIVE: To evaluate the effectiveness of the syndromic approach in management
      of vaginal infections among pregnant women in Moshi urban, Tanzania. METHODS:
      Between June 2002 and March 2004, 2654 pregnant women in their 3rd trimester were
      recruited from two community primary health care clinics. They were interviewed
      using a structured questionnaire, examined and genital samples collected. Vaginal
      secretions were evaluated for bacterial vaginosis (BV) by Amsel's criteria, for
      trichomoniasis (TV) and candidiasis (CA) by wet mount microscopy. Sensitivity,
      specificity, and positive and negative predictive values were used to assess the
      effectiveness of syndromic management for vaginal infections. RESULTS: The
      prevalence of TV, BV and CA were 5.0%, 20.9% and 11.4% respectively. Nearly 70%
      of the vaginal infections with trichomoniasis and/or bacterial vaginosis were
      asymptomatic. Self reported vaginal discharge or the presence of vaginal
      discharge during examination were poor predictors of vaginal infections with a
      sensitivity of 29%-54% and 26%-50% respectively in detecting TV and BV. Using
      them would lead to under-diagnosis of those with these infections and
      overtreatment of those without the infections. CONCLUSIONS: Diagnosis and
      treatment of TV and BV among pregnant women remains a challenge in this setting.
      The current symptom-directed treatment would miss a substantial proportion of TV
      and/or BV infections because of the poor performance of the test, and because
      most infections were asymptomatic or unrecognized. The introduction of simple,
      point of care laboratory screening tests for vaginal infections into routine
      antenatal care at primary health clinics with laboratory facilities should be
      considered.

PMID- 20803917
TI  - Prevalence and determinants of hypertension in the urban and rural population of
      a north Indian district.
AB  - BACKGROUND: Hypertension is a major contributor to the cardiovascular morbidity
      and mortality in industrialized countries. Reports suggest that hypertension is
      rapidly increasing in developing countries like India. Non-communicable diseases
      are likely to overshadow infectious diseases in the coming years and pose a heavy
      strain on health budgets in our country. In this study we have tried to study the
      prevalence of hypertension in a north Indian population based on the recently
      formulated criteria of the JNC-7 and to identify the determinants of
      hypertension. OBJECTIVES: (1) To determine the prevalence of hypertension in the
      urban and rural population of Lucknow District. (2) To study the relationship of
      hypertension with age. (3) To study the determinants of hypertension in the urban
      and rural population of Lucknow District. SETTING AND DESIGN: A community-based
      cross-sectional study was conducted in four randomly selected areas in urban and
      rural parts of Lucknow district, respectively. Two-stage stratified random
      sampling technique was used. METHODS: We studied 800 subjects (355 men, 445
      women) aged 20 years and above, 400 from urban area and 400 from rural area of
      Lucknow district. A pre-tested structured questionnaire was used to elicit the
      required information from the study participants and the diagnostic criteria for
      hypertension were taken according to the Seventh Joint National Committee Report
      on Hypertension (JNC-7). STATISTICAL ANALYSIS: Pearson's Chi-square test,
      Student's t-test, and multiple logistic regression. RESULTS: The prevalence of
      hypertension was 32.8% in the urban population and 14.5% in the rural population.
      The mean blood pressures were 128.4 +/- 18.8 mmHg systolic and 82.6 +/- 10.2 mmHg
      diastolic in urban area and 120.5 +/- 16.1 mmHg systolic and 77.8 +/- 8.8 mmHg
      diastolic in rural area. A significant correlation of blood pressure with
      increasing age was seen. In urban area, hypertensives were less physically
      active, and more likely to smoke and consume alcohol. About 9.2% of the
      hypertensives had coexisting diabetes mellitus. Mean weight, BMI and waist
      circumference of hypertensives was significantly higher, whereas there was no
      significant difference between mean heights. In rural area, similar association
      was seen except alcoholism and diabetes. Multivariate logistic regression showed
      that regardless of area, age and gender, were significant risk factors of
      hypertension. In the urban population, diabetes (OR = 6.917) and BMI (OR = 1.195)
      and in the rural population, physical activity (OR = 0.483) and waist
      circumference (OR = l.094) were significantly associated. CONCLUSIONS: A high
      prevalence of hypertension was seen in the urban and rural population of a north
      Indian district Risk factors of hypertension were age and gender in urban as well
      as rural population. Diabetes, higher BMI values, decreased level of physical
      activity and increased waist circumference also significantly contributed to the
      risk of hypertension, which necessitates intervention at the primary health care
      level for its prevention.

PMID- 20803918
TI  - Sexual risk behaviour of street youths in south west Nigeria.
AB  - OBJECTIVES: Previous studies have mainly focused on sexual behaviour of in-school
      Nigerian youths with little attention to those on the street. This survey was
      conducted to determine the sexual risk behaviours of young people on the streets
      of Ibadan, Nigeria. METHODOLOGY: A cross sectional survey was conducted among
      youths aged 15-24 years in the major markets, motor parks and commercial areas in
      two local government areas in Ibadan. Participants in the study areas were
      identified in groups based on their occupational activity and all consenting
      young people were interviewed. A semi-structured questionnaire was used to obtain
      information on sexual behaviours, condom use and history of sexually transmitted
      infections. Data was managed using SPSS version 11. RESULTS: Most (68.8%) were
      males, 79.0%, were sexually experienced, the median age at sexual debut for males
      was 15 years and 16 years for females. More females (53.9%) compared to (34.5%)
      males reported that their first partners were five or more years older, p < 0.01.
      Condom use during the first sexual intercourse was reported by only 32.2%. Sex
      with a commercial sex worker or exchange of sex for money was reported by 18.2%
      (20.6% of males versus 12.2% of females, p = 0.01). Factors significantly
      associated with history of transactional sex were; male gender; older age (20-24
      years); being out of school and regular alcohol use. Multiple sexual partnering
      was reported by 58.2%, the significant predictors were male gender; early age at
      sexual debut; regular alcohol use and history of transactional sex. Inconsistent
      condom use was reported by 44.8%, the predictors were female gender; regular
      alcohol use and history of transactional sex in the previous year. CONCLUSION:
      Majority of these young people on the streets are sexually active and many engage
      in high risk sexual behaviours. Development of appropriate sexual and
      reproductive health interventions is recommended.

PMID- 20803919
TI  - Insights on hiv pre-test counseling following scaling-up of PMTCT program in
      rural health posts, Burkina Faso.
AB  - BACKGROUND: Quality of pre-test counseling in empowering women to make informed
      decisions related to HIV/AIDS is regarded as a key element to ensure
      effectiveness of PMTCT interventions. This cross-sectional study examined how
      well HIV testing services with 'Opt in' strategy are being delivered following
      scaling-up of PMTCT programs in rural peripheral health centers in Burkina Faso.
      METHODS: We observed the process of HIV testing service delivery and evaluate 19
      pre- test counseling sessions linked with 16 in-depth interviews with the
      pregnant women. We also conducted interviews with 6 counselors, district health
      officer and the PMTCT coordinator. Secondary data on acceptance of HIV testing
      were collected from each study site. RESULTS: The district authority
      decentralized the implementation of PMTCT service to the peripheral health
      facility. No health center has on spot HIV testing facility. The proportion of
      pregnant women agreed to join pre test counseling was very low (7%-29%).
      Acceptance of HIV testing after PTC was as high as 100%. There is a substantial
      gap between the standards set by the National Guidelines and the actual practice
      of conducting the counseling sessions. Major barriers for health workers were
      lack of training, disruption of service, work load, difficulties to discuss risk
      behavior with women and lack of partner involvement. Interviewed women were
      satisfied with the services and majority wanted to disclose their HIV status.
      CONCLUSION: Our findings warrant regular supervision with refresher training and
      a focus on quality counseling would help health workers to enhance their
      performance and support them to comply with the program. Encouraging women to
      engage in a discussion about testing with their partners with male involvement
      activity in the community could improve couple testing. Strengthening group
      counseling and reorganizing the strategy including introduction of on site rapid
      HIV testing could effectively improve coverage.

PMID- 20803920
TI  - Prevalence and risk factors for trachoma in Rwanda.
AB  - OBJECTIVE: Trachoma is the oldest blinding ocular infection that has well known
      predisposing risk factors for its transmission. The prevalence of trachoma in
      Rwanda has been unknown as no trachoma population-based survey had ever been
      undertaken. The aim of this study was to determine the prevalence of Trachoma and
      assess associated risk factors for its transmission. METHODS: A population-based
      cross-sectional study of children aged 1 to 9 years and adult women aged 15 and
      above. Study setting was Gatsibo (Eastern Province) and Nyaruguru (Southern
      Province) Districts, Rwanda. Clusters were selected through probability
      proportion-to-size sampling and eligible persons were sampled using a systematic
      random sampling method. Data were collected using three generic survey
      questionnaires (village, household and individual level) as recommended by the
      World Health Organization (WHO). RESULTS: 3451 children and 1,841 adult women
      underwent ocular examination for trachoma assessment. The prevalence of
      trachomatous inflammation-follicular (TF) among children was 1.32% [95% CI, 0.77
      1.86] in Gatsibo and 0.73% 195% CI, 0.33-1.13] in Nyaruguru Districts,
      respectively; with both districts having a prevalence below the WHO/International
      Trachoma Initiative (ITI) cut-off point of 10% for trachoma to be taken as
      disease of public health importance. There was no case of blinding trachomatous
      trichiasis and corneal opacity in both districts. Risk factors present for
      trachoma transmission were minimal. CONCLUSION: Trachoma is not a disease of
      public health importance in Gatsibo and Nyaruguru Districts in Rwanda

PMID- 20803921
TI  - Availability of antimalarial drugs and evaluation of the attitude and practices
      for the treatment of uncomplicated malaria in Bangui, Central African Republic.
AB  - National malaria management policy is based upon the availability of effective
      and affordable antimalarial drugs. This study was undertaken to evaluate the
      quality of the treatment of uncomplicated malaria cases in Bangui, an area with
      multi-drug resistant parasites, at a time preceding implementation of a new
      therapeutic policy relying on the artemisinin derivative combined treatment
      artemether-lumefantrine. A cross-sectional study was carried out in Bangui city
      to assess availability of antimalarial drugs and the performances of health
      workers in the management of uncomplicated malaria. Availability of drugs was
      recorded in all drugs wholesalers (n=3), all Pharmacies in health facilities
      (n=14), private drugstores (n=15), and on 60 non official drug shops randomly
      chosen in the city. Despite a limited efficacy at the time of the survey,
      chloroquine remained widely available in the official and non official markets.
      Artemisinin derivatives used in monotherapy or in combination were commonly sold.
      In health care facilities, 93% of the uncomplicated malaria cases were treated in
      the absence of any laboratory confirmation and the officially recommended
      treatment, amodiaquine-sulfadoxine/pyrimethamine was seldom prescribed. Thus, the
      national guidelines for the treatment of uncomplicated malaria are not followed
      by health professionals in Bangui. Its use should be implemented while a control
      of importation of drug has to be reinforced.

PMID- 20803922
TI  - Iodine status and cognitive function of women and their five year-old children in
      rural Sidama, southern Ethiopia.
AB  - OBJECTIVE: Iodine deficiency is one of the most common micronutrient deficiencies
      worldwide and is a major cause of preventable mental retardation. The purpose of
      this study was to assess the iodine status and cognitive function of women of
      childbearing age and their five-year-old children. METHOD: A cross-sectional
      study was conducted in a rural village in southern Ethiopia. A convenience sample
      of one hundred women and their five year-old children participated in the study.
      Goiter grade, urinary iodine excretion, Raven's CPM and cognitive tests from the
      Kaufman ABC-II, were administered to the women and their children. RESULTS: The
      use of iodized salt was only 2%. The mean iodine content of water in and around
      the study area was 4.46 microg/l. Occurrence of goiter was 85% in the women and
      33% in children. Urinary iodine excretion for all participants was <49 microg/L,
      the top of the range for moderate iodine deficiency. The median urinary iodine
      excretion (UIE) was 1 microg/L for both mothers and children. For children,
      measures of short term memory (Sequential index) were correlated with the visual
      processing (Simultaneous index) (r = 0.49, p < 0.0001). Goiter and urinary iodine
      excretion were correlated to Sequential index (r = 0.39, p = 0.0011 and r = 0.2,
      p = 0.05) respectively, but not to the Simultaneous index for children.
      Sequential (r = 0.21, p = 0.03) and Simultaneous (r = 0.29, p = 0.004) indices of
      mothers and children were correlated. CONCLUSION: The high prevalence of goiter
      and the low urinary iodine excretion demonstrate serious long- and short-term
      iodine deficiency in the study area. Relations between measures of iodine status
      and short term memory in children raise concern about potential functional
      effects of iodine deficiency.

PMID- 20803923
TI  - Schistosoma mansoni infection among patients visiting a health centre near Gilgel
      Gibe Dam, Jimma, south western Ethiopia.
AB  - OBJECTIVE: Schistosomiasis is a global parasitic disease and ranks second to
      malaria in terms of socioeconomic and public health importance in tropical and
      subtropical areas. It is a disease which remains a major health problem due to
      the lack of vaccines, the failure to eradicate the mollusc vector and the recent
      development of parasite resistance to antischistosome drugs. A cross-sectional
      study was conducted to determine the prevalence of Schistosoma mansoni infection
      among patients visiting Assendabo health center, nearby Gilgel Gibe hydroelectric
      dam, South-Western Ethiopia. RESULTS: From the total of 198 patients with stool
      sample 21 (10.61%) were positive for Schistosoma mansoni infection. Of the
      infected subjects, 11.6% had contact with water for one or more reasons.
      CONCLUSION: The severity of infection and subsequent impact on the socio-cultural
      condition needs appropriate control measures especially where the water body
      which can act as habitat for the intermediate host is available.

PMID- 20803924
TI  - Mass media and sexual health behaviour of college students in Nigeria: a study of
      Lagos State University.
AB  - This paper examines the effects of mass media on the sexual health behaviour of
      single college students in Nigeria. Simple random sampling procedure was adopted.
      A total of 300 pre-coded questionnaires were administered in study population.
      Data analysis reveals that the respondents are more frequently exposed to the
      internet (75%), TV (77%) and radio (75%). More frequent exposure to print, home
      video and internet media are significantly related to rising level of sexual
      activities among female respondents. Frequent exposure to radio (over 3 times)
      and internet (4 times) are more likely to influence condom use positively among
      male respondents. Among their female counterparts, more frequent internet
      utilization (almost twice) is more likely to raise the level of condom use. Thus,
      an international accord on the content of the mass media, especially on their
      moral implications for the younger generation is imperative.

PMID- 20803925
TI  - Wait time and service satisfaction at Antenatal Clinic, Obafemi Awolowo
      University Ile-Ife.
AB  - OBJECTIVE: Antenatal care is an essential aspect of health care delivery for
      improving pregnancy outcome such that about two-thirds of maternal deaths can be
      prevented. The study was carried out with the aim to assess patient satisfaction
      on some aspects of antenatal care services (timeliness, courtesy, communication
      and competence of personnel in the clinic) and estimated time spent in clinic.
      METHODOLOGY: The study was a cross sectional survey of pregnant mothers attending
      antenatal clinic of the Obafemi Awolowo University Teaching Hospital Complex
      within the period of the study. The patients who were willing to participate in
      the study were recruited and interviewed with pretested questionnaire. Direct
      observation of the total time spent clinic was also conducted. RESULTS: Four
      hundred pregnant mothers were recruited and interviewed. 55% were satisfied with
      the quality of health talk, 72.6% were of the opinion that the services of the
      hospital are good and meet their needs and 87% agreed with the quality of health
      talk. 53.7% agreed with the competency of the hospital staff, 39.1% agreed with
      timely response of the staff and 20.5% were of the opinion that the staffs were
      friendly and polite. The socio-demographic factors that significant influenced
      the respondent's satisfaction of the antenatal services and time spent in clinic
      were educational and occupational status. The total time spent in the clinic was
      2hrs 42 mins of which 1 hr 40 was spent at the nurse's desk, 13 minutes for
      consultation with the doctor and the rest for laboratory services, record
      services. The transit time before consultation with nurses and doctors were 51.2
      minutes and 2 hr 29 mins respectively. CONCLUSION: Majority of respondents were
      satisfied with the care received, however long waiting times is the norm of
      antenatal care services

PMID- 20803926
TI  - The quality of food, clothing and shelter provided to orphaned children under
      foster care in Kibera slums in Kenya.
AB  - OBJECTIVE: To assess the quality of foster care with regard to the provision of
      food, clothing and shelter to orphaned children under foster care. SETTING:
      Kibera Division in Nairobi, Kenya. METHODOLOGY: This was a cross-sectional
      survey. A total of 82 respondents were obtained using the Snowball Sampling
      Technique. Focus Group Discussions were conducted with 37-orphaned children who
      were studied in 4 separate groups of males and females. Eighteen (18) Key
      Informants were interviewed. A questionnaire was used to collect Quantitative
      data from foster care providers. Qualitative data was obtained by using Focus
      Group Discussion Guides and Key Informant Interview Guides. RESULTS: Nearly 49%
      of the foster care providers rated food quality as fair while 29.3% of them
      reported poor quality. The majority of the orphaned children had only one meal
      per day while others did not get any food at home. Over 73% of the foster care
      providers reported that the children's clothing was inadequate. About 90% of the
      foster care providers lacked adequate shelter. The number of people sharing the
      same shelter had a Mean of 6, = 2 Standard Deviation. Overcrowding explains
      episodes of pneumonia and 83% cases of coughs and colds among the orphaned
      children. Over 56% of the foster care providers live below the poverty line.
      Nearly 10% of the respondents provided foster care to at least 5 orphaned
      children. The Mean number of orphaned children was 2.2 per household in 2005, an
      increase from 1.9 in 2004, with a Median of 3, +/- 1.3 Standard Deviation.
      CONCLUSION: The quality of foster care is poor and the quantity is inadequate.
      There is evidence that families are struggling to provide adequate and good
      quality of food, clothing and shelter to orphaned children, exposing them to the
      risk of malnutrition, low self-esteem and respiratory tract infections.

PMID- 20803927
TI  - Social marketing and the fight against malaria in Africa: population services
      international (PSI) and insecticide treated nets (ITNS).
AB  - This textual analyses on Social marketing, Insecticide Treated Nets (ITNs) and
      Population Services International (PSI) were undertaken to achieve two
      objectives: (a) to contribute to the continuing debate and search for a better
      strategy for combating malaria in sub-Saharan Africa; and (b) to contribute to
      theory building on social marketing. The analyses revealed that Malaria has
      reached an epidemic proportion and despite major inroads by PSI in combating
      malaria on the principles of social marketing, the strategies of pricing and
      segmentation of the clients are not appropriate for Sub-Saharan African countries
      that are mired in absolute poverty where majority of the rural communities eke a
      living on less than a dollar per day and the health sector does not receive
      priority attention from policy makers and politicians. The descriptive statistics
      and a one sample t test for the sampled countries suggest that sub-Saharan
      countries have not even met the hypothesized 5% investment of their GDP on
      health, compared to their counterparts, the developed countries, who are all
      above this figure. The null hypothesis that there is no significant different
      between the population and the sample means of both developed and a developing
      country in their investments in the health sector was also tested and rejected.
      Though the elements in some of the existent models and theories of social
      marketing such as Health Belief Model, Theory of Reasoned Action, Social
      Cognitive Theory and Trans-theoretical Models all attempt to advocate for
      elimination of constraints and barriers to effective access to a service or
      product, PSI is adamant to these and try to generalize these principles in all
      contexts, including in Sub-Saharan Africa. The African scenario, where about 90%
      of Malaria related deaths cases in the world occur, demands more than what these
      theories present. Accordingly, it was concluded that however good intentioned
      social marketing is, in the case of ITNs in this region, it is counter productive
      as the pricing de-motivates clients who usually have other pressing needs to
      address and segmentation limits coverage. Social marketing is thus more relevant
      to developed economies where absolute poverty no longer exist and people can
      afford to pay for health services. Malaria in sub-Saharan Africa needs a "carpet
      bombing" strategy. It was also concluded that for Sub-Saharan countries to
      effectively address the MDG six on malaria, and implement the Abuja Summit and
      the Roll Back Malaria partnership declarations, it requires a high degree of
      political commitment, amongst others, to enable the vulnerable communities have
      access to free malaria treatment related drugs. Partners in the fight against
      malaria such as PSI should adopt a more eclectic intervention strategy, and be
      cognizant of the fact that the strategy that works for Africa should be that
      which is based on strict equity and stimulates demand for ITNs. The paper
      concludes by agreeing with Professors Curtis and Sachs that comprehensive malaria
      control in Africa is achievable by 2010, at the minimal cost if sound principles
      of public health and economics are observed. Millions of lives can be saved and
      Africa will be given vital help in escaping from the viscous circle of poverty
      and diseases that continue to grip the continent. The target for all intervention
      efforts should be to eliminate the cost factor and ensure free distribution of
      all malaria related treatment products.

PMID- 20803928
TI  - Costing resource gaps for the delivery of minimum essential health services
      package in the Coast Province, Kenya.
AB  - OBJECTIVE: The study aims to determine the resource gaps in the delivery of MEHSP
      at the district health system. DESIGN: Cross sectional survey. SETTING: District
      health system, Coast Province, Kenya. SUBJECTS: A sample of 11 district health
      system facilities. RESULTS: Resource gaps analysis shows that service provision
      is sensitive to dominant inputs (availability of buildings, equipment, personnel,
      drugs and non-pharmaceuticals) at all levels of care. Targeting of the resources
      in respect of the important inputs is poor at all levels as demonstrated by the
      wide range of excess and shortages of inputs. The mismatch may have adverse
      effects on both quantity and quality of services. CONCLUSION: A deliberate policy
      for targeting of finances for the important inputs needs to be developed to
      ensure optimisation of their combinations for minimization of mismatch of
      resources.

PMID- 20803929
TI  - The final hurdle to be crossed in the eradication of dracunculiasis in Nigeria.

PMID- 20803930
TI  - Circumcision and hemophilia in developing countries.

PMID- 20803931
TI  - Pain in the older adult.

PMID- 20803932
TI  - Preparing geriatric nurses of the future... today.

PMID- 20803933
TI  - [Today challenges for internal medicine specialists].

PMID- 20803935
TI  - [Molecular aspects of antineoplasic action of vitamin D].
AB  - The effects of the environment, particularly dietary factors, may influence in
      the development and prevention of cancer. Vitamin D (colecalciferol) has been
      associated for years with calcium homeostasis regulation, but many
      epidemiological, biochemical and genetic studies reveal non classic effects of
      vitamin D, such as vitamin D involvement in the progression of different types of
      cancer. The aim of the present article was to give a review about the molecular
      mechanisms of the antineoplasic action of vitamin D. These effects are still not
      completely established, but it is well known that vitamin D induces cellular
      arrest, triggers apoptotic pathways, inhibits angiogenesis and alters cellular
      adhesion. To maintain suitable vitamin D levels seems to be necessary for many
      physiological processes, and not only for bone homeostasis. Clinical studies
      might determine vitamin D levels that can also protect against the cancer
      development.

PMID- 20803934
TI  - [Scores to predict the number of hospitalization days in a general ward at a
      tertiary hospital].
AB  - Although most usual admissions to hospital are in rooms in general wards, there
      are not scores to predict the number of hospitalization days in this area. The
      patients are located based on diagnosis at admission. AIM: to make scores who
      predict the number of hospitalization days in the general wards. METHODS: We
      studied all the patients who were admitted to the Italiano Hospital from march of
      2004 to may of 2005 in Cordoba city (Argentina). The inclusion criteria were:
      more than 18 years old patients who were admitted for more than 24 hours due to
      clinical or surgical conditions in general wards. We evaluated 53 variables
      including background, toxics, physiologic and demographic data, social reports,
      nutritional condition, out patients previous consultations at the admission day.
      Died patients were not included in this score analysis. RESULTS: The number of
      patients included was 1003. Short hospitalization was considered when the number
      of the days of the hospitalization was less than 4 days and long hospitalization
      was more than 5 day in a general ward. We made a score with 11 main variables
      according to physician clinical perception. The statistical analysis was not
      significant in each variable studied. When we analyzed the score with 11 of them
      as a whole, it showed statistical significance. We divided in categories and
      pointing according to statistic settlements. Minimum pointing: 11; maximum: 33.
      Showed R2: 0,77 ( p: 0,06) between pointing and the hospitalization days.
      CONCLUSION: The lower scores were related with a high chance of discharge before
      5 days. This score may be a simple and feasible tool for the hospital
      administration and for the prediction of available beds in a general wards.

PMID- 20803936
TI  - [Pulmonary alveolar proteinosis: report of two cases and review of the
      literature].
AB  - Pulmonary alveolar proteinosis is a rare disease characterized by extensive
      radiological and tomographic pulmonary lesions and a variable clinical picture
      ranging from pulmonary insufficiency to spontaneous remission. Among its three
      described forms, the so called Idiopathic or Adult form is responsible for more
      than 80% of published cases. It's physiopathology depends on an autoimmune
      process directed against the GM-CSF (Granulocite Macrophage- Colony Stimulating
      Factor) that induces a functional defect of the macrophage with consequent
      intraalveolar accumulation of surfactant. Pulmonary and extrapulmonary
      infections, are common, often with unusual pathogens. Diagnosis can be made from
      the combination of clinical, radiological and bronchoalveolar lavage data,
      although sometimes histopathologic material is needed for confirmation. Total
      pulmonary lavage is currently the treatment of choice. Mortality is usually low
      and related mostly to infectious complications. We hereby describe our experience
      with two patients.

PMID- 20803937
TI  - [Medicine and humanities].

PMID- 20803938
TI  - Chronic administration of nonsteroidal-antiinflammatory drugs (NSAIDS): effects
      upon mouse reproductive functions.
AB  - Although nonsteroidal-antiinflamatory drugs (NSAIDs) are widely employed,
      reproductive side effects of prostaglandins long-term inhibition remain unknown.
      The objective of the present study was to evaluate the effects of chronic
      low/moderate NSAIDs doses upon mice reproductive functions. Male or female mice
      were injected (i.p. for 60 or 35 days respectively) with: ibuprofen doses A, B or
      C (0.56, 1.12 or 1.68 mg/100 g/day respectively) or piroxicam doses A, B or C
      (0.028, 0.056 or 0.084 mg/100 g/day respectively). Parameters evaluated were: a)
      in females, spontaneous and induced ovulation, oocyte maturity and spermatozoa
      migration through genital tract, b) in males, epididymal spermatozoa
      concentration, motility, viability, resistance to hypoosmotic shock, acrosomal
      status and membrane maturity and c) in both genders, in vitro and in vivo
      fertilization, reproductive hormones plasma levels and cyclooxigenase inhibition
      in reproductive tissues. In females ibuprofen (dose A) elicited a significant
      reduction in spontaneous and induced ovulation rates and piroxicam (dose A)
      diminished the concentration of spermatozoa found in the uterus after mating.
      Males treated with ibuprofen (dose B) showed a reduction in the in vitro
      fertilization ability. Our data reveal that chronic administration of ibuprofen
      or piroxicam can exert detrimental effects upon reproductive physiology, which
      depends on the doses and/or the drug employed.

PMID- 20803939
TI  - [The haemolytic uraemic syndrome].
AB  - Recent advances in understanding the aetiology of the disorders that make up the
      haemolytic uraemic syndrome (HUS) permit a revised classification of the
      syndrome. With appropriate laboratory support, an aetiologically-based subgroup
      diagnosis can be made in all but a few cases. HUS caused by enterohaemorrhagic
      Escherichia coli remains by far the most prevalent subgroup, and new insights
      into this zoonosis are discussed. The most rapidly expanding area of interest is
      the subgroup of inherited and acquired abnormalities of complement regulation.
      Details of the pathogenesis are incomplete but it is reasonable to conclude that
      local activation of the alternative pathway of complement in the glomerulus is a
      central event. There is no evidence-based treatment for this diagnostic subgroup.
      However, in circumstances where there is a mutated plasma factor such as
      complement factor H, strategies to replace the abnormal protein by plasmapheresis
      or more radically by liver transplantation are logical, and anecdotal successes
      are reported. In summary, the clinical presentation of HUS gives a strong
      indication as to the underlying cause. Patients without evidence of EHEC
      infection should be fully investigated to determine the aetiology. Where
      complement abnormalities are suspected there is a strong argument for empirical
      and early plasma exchange, although rapid advances in this field may provide more
      specific treatments in the near future.

PMID- 20803940
TI  - [Peripartum cardiomyopathy: a rare clinical condition].
AB  - INTRODUCTION: Peripartum cardiomyopathy (PC)is a heart failure associated with
      pregnancy, which has the following criteria to establish its clinical diagnosis:
      1 - this pathology in the last month of pregnancy or in the first five months
      postpartum. 2 - No etiology determinant of heart failure. 3- Absence of
      demonstrable heart disease before the last month of pregnancy. 4 - Deterioration
      of the left ventricular systolic function demonstrated by Eco cardiography.
      Patients and methods. Descriptive, simple cross and retrospective. We reviewed
      all the clinical records of pregnant women and mothers who were admitted for
      hospitalization in intensive care services diagnosed with congestive heart
      failure between February 1999 and February 2007 RESULTS: The number of patients
      with heart failure were 23, 7 of them were diagnosed of PC, 5 pregnant mothers
      and 2 puerperal women. The PC patients age was between 20 and 37 years, with an
      average of 31 years. The average of ejection fraction evaluated by an echo
      cardiograph was 32.8%, 4 women with < 30% and 3 with > 30%. The route of
      termination of pregnancy was not influenced by the disease, and only for
      obstetric indications, 5 by caesarean section and 2 by vaginal births. All the
      newborn were with appropriate weights to gestational age, with Apgar scorer
      normal. There were no maternal deaths, or neonatal fetus. The incidence of
      pathology turns out to be 1/7500 born live.

PMID- 20803942
TI  - [Accelerated atherosclerosis in autoimmune diseases].

PMID- 20803941
TI  - [Malignant melanoma of the oral cavity].
AB  - Malignant melanoma of the oral cavity is a rare neoplasm and it is only 0.5% of
      the malignant neoplasms of the oral cavity, and less than 10% of all the
      malignant melanomas. The mean age for patients with oral melanoma is from 40 to
      70 years; with a higher frequency between the 50 and 60 years. Pigmentation areas
      are frequently noted before diagnosis of this neoplasm. Some predisposing factors
      are mechanical traumas resulting from not well adapted prostheses, solar
      radiation, and chem-icals. Although oral cavity melanomas can remain asymptomatic
      during a time, the clinical presentations include hemorrhage, ulceration and
      pain. Melanomas grow fast, generally in a vertical growth phase, with early
      invasion of bones and lymphatic nodes. The prognosis for patients with melanoma
      is poor with a 5-year survival rate. The election treatment is surgical. The
      early diagnosis, the recognition of the lesions for doctors and odontologists,
      and the biopsy of recent or old pigmentation areas in the mouth that they have
      some changes (ulceration, bleeding, etc.) will contribute to offer patients a
      more effective treatment and a higher survival rate. We will present the case
      study of a 78-year-old male patient with a tumor in the dental ridge surrounded
      by melanotic spots, which was diagnosed as invasive melanoma and confirmed with
      immunohistochemical techniques.

PMID- 20803943
TI  - [Infective endocarditis. Systematic review of twenty years of performances in the
      Sociedad Argentina de Medicina].
AB  - Infective endocarditis (IE) is still a disease with high morbidity and mortality.
      Its diagnosis and treatment are still a major challenge in clinical practice.
      There have been very few studies published about IE in Argentina. METHODS: We
      reviewed all the studies about IE published in the Argentine Medicine Society
      from 1980 to 2003 and we analyzed demographic, clinical and bacteriological data.
      RESULTS: 27 studies with 628 patients were included. Mean age of patients was
      50.7 years old. The most frequent clinical data were fever, murmur and elevated
      sedimentation rate. Stafilococcus spp was the most common causative organism,
      followed by streptococcus spp. The echocardiographic demonstration allowed the
      definitive diagnosis in 2/3 of the patients. CONCLUSION: The IE data of Argentina
      are not different from other data published in different countries and this study
      shows some clinical features of IE in Argentina.

PMID- 20803944
TI  - Genetics of obesity.
AB  - BACKGROUND: Obesity is a complex phenomenon that involves interactions between
      environmental and genetics factors. The genetic studies in animal models and
      humans has allowed great progress in the knowledge of body weight regulation.
      Identifying the hypothalamic leptin/melanocortin pathway as critical in many
      cases of monogenic obesity has permitted targeted, hypothesis-driven experiments
      to be performed, and has implicated new candidates as causative for previously
      uncharacterized clinical cases of obesity. DATA SOURCES: Narrative review.
      PubMed, Lilacs and ScieLo databases were searched with the terms "obesity",
      "genetics" and limited only for" all child 0-18 years". RESULTS: Numerous studies
      in children and adolescents, have tried to identify candidate genes. At present,
      the results are not conclusive. Thus, is yet premature genotype obese child on a
      large scale for predictive testing. Meanwhile, the effects of mutations in the
      melanocortin-4 receptor gene, for which the obese phenotype varies in the degree
      of severity among individuals, are now thought to be influenced by one's
      environmental surroundings. Molecular approaches have revealed that syndromes
      previously assumed to be controlled by a single gene are conversely regulated by
      multiple elements. CONCLUSIONS: When specific treatments based on recent
      discoveries become available, genetic testing could help to discriminate
      different types of obesity that may respond differentially to therapeutic
      measures.

PMID- 20803945
TI  - [Cutaneo-viscero-hemolytic loxoscelism with acute renal failure].
AB  - The Loxoscelism is caused by the bite of spider Loxosceles laeta gender, of
      worldwide distribution. The poisoning can cause lesions dermonecrotic and less
      frequently a systemic illness that can be fatal. The mechanism of venom action is
      multifactorial. The characteristic dermonecrotic lesion results from the direct
      effects of the venom on the celular and basal membrane components, as well as the
      extracelular matrix. The initial interaction between the poison and tissues,
      causes complement activation, migration of polymorphic neutrophils, liberation of
      proteolytic enzymes, cytoquines, aggregation platelet, and blood flow alterations
      that result in edema and ischemia, with development of necrosis. There is no a
      definitive treatment for loxoscelism. However, the value of specific antivenom,
      to decrease lesion size and limit systemic illness even when such administration
      is delayed. We present a case of cutaneous-visceral loxoscelismo with unfavorable
      evolution.

PMID- 20803946
TI  - [Immunophysiological mechanism of origin and maintenance of tumor growth in
      humans].
AB  - A new concept of malignant tumor growth is presented. In consists in the fact
      that the tumor cells in the body occur in specific immune tolerance. As s result,
      they form around the center of regeneration, which consists of activated towards
      the regeneration cells of the immune system, which support the formation and
      growth of the tumor. In the early stages of differentiation, precancerous cells
      are not able to attract immune cells and form the focus of regeneration, so the
      majority of them die. At the outbreak of chronic inflammation, which contains a
      high percentage of regeneration of activated immune cells, the conditions exists
      for the formation of a focus of regeneration and, hence, growth and activation of
      precancerous cells and their transformation into high-grade malignant cells. This
      concept defines new approaches to treatment. For effective cancer therapy is
      necessary to neutralize the regenerator chamber in the tumor tissue. The
      effectiveness of the regeneration of damaged human tissues can be achieved
      through regenerator chamber similar to that created in the malignant tissue, and
      the introduction of a stem cell.

PMID- 20803947
TI  - [Gamma-activity of the cerebral cortex: communication with intelligence and
      accuracy of perception of time].
AB  - Connection of indicators of intelligence and accuracy of perception of time is
      established with level cortical interactions on frequency of a gamma rhythm, and
      also phase parities between a gamma rhythm and low-frequency components EEG.
      Character of these communications differs at young men and girls, depends on a
      frequency range of a gamma rhythm, a kind and a stage of carried out activity.

PMID- 20803948
TI  - [Features of cognitive audiory evoked potentials changes at participants of
      liquidation of chernobyl accident consequences the message II. the analysis of
      late component P300].
AB  - At 10 participants of liquidation of consequences of Chernobyl accident (middle
      age 50.5 +/- 4.0 years) and at 10 healthy persons (middle age 47.0 +/- 6.0 years)
      are performed complex neuropsychological examination and registration acoustical
      cognitive evoked potentials (EP) using odd-ball paradigms. Neuropsyhological
      research has revealed at liquidators disorders of the higher mental functions,
      such as aspontanity, decrease speech and a visual memory, and also deficit of
      higher motor functions. According to the analysis of amplitude-time
      characteristics of component P300 acoustical cognitive EP a decrease in amplitude
      of this component at liquidators in all areas of the brain, for both experimental
      situations for all stimulus in comparison with healthy persons the same age was
      revealed. At the analysis of latent period (LP) P300 at liquidators the most
      distinct increase was revealed in a situation of passive listening for all kinds
      of stimulus. The analysis of reactivity of LP in different experimental
      situations has shown that at healthy persons during passive listening had similar
      values for all kinds of stimulus, and an account situation the maximum values-
      for significant stimulus. For liquidators the type of reaction in the form of
      increase in LP values at the majority of stimulus in both experimental
      situations. The analysis of regional LP changes of component P300 has found out
      the maximum distinctions between groups in frontal area of the left hemisphere.
      Along with it at liquidators the type the reactions similar for all shown
      stimulus without dependence from their importance in comparison with norm is
      revealed "uneconomical, superfluous". It can testify about decreasing of
      attention and memory reserves and to promote disorder of the higher mental
      functions. The described of amplitude-time characteristics of component P300 of
      acoustical EP at liquidators EP can testify to delay of perception, processing
      and the information analysis in a combination to easing of inhibitory processes
      leading to the higher mental dysfunctions. The obtained data have similarity to
      people of old age, supporting a hypothesis about the accelerated ageing of a
      brain, and also about pathological development of processes of ageing as a result
      of influence of low doses of radiation.

PMID- 20803949
TI  - [Auditory perception sluggishness during short moving sound image localization].
AB  - Displacement of the perceived position of the starting points relative to the
      objective one during the moving sound source localization is an example of the
      auditory perception sluggishness. The ability to localize starting and end points
      of sound image trajectories was studied in comparison with stationary sound image
      positions. Sound images moved gradually or abruptly to the left or right from the
      head midline. The subjects were asked to estimate the position of the virtual
      sound source, using the graphic tablet. It was revealed that the starting points
      shifted systematically in the direction of the sound image movement. This
      tendency was stronger for the gradual movement then for the abrupt shift, and for
      shorter stimuli (100 ms) in comparison with longer ones (200 ms). The starting
      point displacement magnitude depended on the final value of the interaural time
      delay. The findings are discussed in view of the "snapshort" and "movement
      detectors" theories. The representational momentum and anticipation ability of
      the auditory perception were also considered.

PMID- 20803950
TI  - [Directed cortico-cortical functional connectivity at the earlier stages of
      serial learning in adults and children of 7-8 years old].
AB  - The serial learning at its earlier stages that presumably involve working memory
      was studied in adults and children of 7-8 who were reproducing a sequences of
      discrete movements following the order given by a sequence of visual stimuli. In
      both age groups, the learning curves (latent time vs. trial number) were
      qualitatively similar in shape. The overall shape of the learning curve depended
      on the relative share of fast vs. slow phases of latent time reduction.
      Comparison of cortico-cortical functional connectivity at the prestimulus period
      in the sequence reproduction task vs. the simple visuo-motor reaction task showed
      an overall tendency for an increase in influence of postcentral cortical areas
      accompanied by a reduction in influence exerted by the prefrontal and the central
      cortical areas. In particular, it was typical for adults to show an increase in
      directed influence of TPO cortical areas while in children, an increase of
      directed influence of parietal cortex was also observed. Comparing subgroups with
      different shapes of learning curves showed a difference in the directed
      functional connectivity in those subgroups. The results are discussed with a
      particular focus on the role of working memory retaining the internal
      representations of sequences being learned.

PMID- 20803951
TI  - [The peculiarities of intellectual development of boys and girls of 15-16 years
      old].
AB  - The structure of intelligence in senior adolescents was studied. The analysis of
      intelligence in adolescents of both sexes showed that there are no distinct
      differences in the structure of intellectual development in boys and girls of 15
      16 years old. The significantly better results were marked only in girls memory
      development which can prove the fact that the specific character of cognitive
      development doesn't depend on sex at the last stages of puberty. Significant
      dispersion of individual intellectual characteristics can serve the evidence for
      the high variability of the psychophysiology structure of intelligence in
      adolescents at this ontogenetic stage of development.

PMID- 20803952
TI  - [Features of human cortical pyramidal neurons development during second
      gestational trimester].
AB  - Prenatal ontogeny of human neocortex have distinctive features that make it
      unique. Experimental data obtained on animal models could not be easily
      extrapolated on human corticogenesis of middle and late gestational period. Our
      research was aimed at features of human cortical pyramidal neurons development
      within 16-26 gestational weeks. Material was obtained during legal autopsies.
      Neurons were marked using indirect immunofluorescence with primary antibodies
      against phosphorylated a nd dephosphorylated microtubule associated protein
      MAP2.Expression of this protein marks the beginning of dendrogenesis. Morphotype
      and position of neuron within embryonic cortical layers could be easily
      identified due to abundance of MAP2 in neuron body and dendrites. It was shown,
      that MAP2 positive neurons are identifiable in embryonic cortical layer eV as
      early as 18th gestational week. At 25th gestational week two populations of
      pyramidal neurons are apparent inside cortical plate. In addition to layer eV
      neurons that have had differentiated earlier, layer eIII neurons appears.
      According to fact that differentiating neurons are more vulnerable to damaging
      factors than neuroblasts and mature neurons, our results suggest that critical
      periods for cortico-cortical and corticofugal populations of pyramidal cells
      occurs at different stages of second gestational trimester.

PMID- 20803953
TI  - [Hemodynamic indices of children's cardio-vascular system with due regard for
      their constitutional differences].
AB  - The paper presents the study of adaptation of cardio-vascular system of children
      from 5 to 7 to heightened physical activity with due regard for somatic
      peculiarities of human organism. A careful account is given to reographic and
      cyclo-ergometic methods of research under the physical load of heightened power
      capacities 1 and 1.5 watt per 1 kg body weight. The dosage of physical loads with
      regard for somatic peculiarities of human organism assists the rise in the
      standarts of children's functional training. Considerable increase of functional
      potentialities of children of different somatic types is revealed in the
      exponents of absolute physical efficiency, transient and systolic amount of
      blood. Bigger rise of hemodynamic indices have girls in comparison with boys of
      the same age.

PMID- 20803954
TI  - [Peculiarities of multisegmental monosynaptic responses of leg muscles in
      subjects with lumbar nerve compression].
AB  - There were tested reflex motor responses of 16 simmetrical leg muscles, evoked by
      electric stimulation of lumbar nerve at level of L2-L3- or L3-L4-spinal proceses,
      in group of healthy subjects and that of patients with the sings of lumbar-nerve
      compression. The responses were studied when the subjects were in condition of
      rest. The evoked responses agreed with Ia afferents activation through
      monosynaptic neuronal cicuits. Their monosynaptic nature was demonstrated by
      amplitude changes to conditioning stimulus and to continuing tendon vibration
      applied. It was established that on the background of the studied disorder
      multisegmental monosynaptic responses of leg large distal flexors with a great
      amount of slow motor units suffered most significant modifications.

PMID- 20803955
TI  - [Human temperature portrait and its relations with aerobic working capacity and
      the level of blood lactate].
AB  - In study with participation of 53 healthy men volunteers and infra-red
      thermograph application we obtained data confirming thermal portrait (i.e. skin
      temperature distribution in muscle rest conditions with minimal thermoregulatory
      activation) interrelations with maximal aerobic capacity (r = +0.6) and lactate
      level after critical muscle load (r = -0.7). Acute regional cooling (by 1 minute
      feet placing in ice water) led to temperature rise in certain breast and back
      skin local areas and increase in oxygen uptake, pulmonary ventilation and
      respiratory coefficient. Moreover lactate level in peripheral blood reduced.
      Summarizing obtained results we assume brown adipose tissue (BAT) activity
      influencing on thermal portrait formation in conditions with environmental
      temperature below thermoneutral. This hypothesis permits to explain negative
      correlation between skin temperature and body mass index and 2-fold increase in
      oxygen uptake during acute cold exposure. Nevertheless further investigations are
      needed to clarify physiological mechanisms providing significant correlation
      between skin temperatures in rest thermoneutral conditions on the one hand and
      maximal aerobic capacity, anaerobic threshold and lactate content after critical
      muscle load on the other hand.

PMID- 20803956
TI  - Acute testosterone and cortisol responses to high power resistance exercise.
AB  - This study examined the acute hormonal responses to a single high power
      resistance exercise training session. Four weight trained men (X +/- SD; age
      [yrs] = 24.5 +/- 2.9; hgt [m] = 1.82 + 0.05; BM [kg] = 96.9 +/- 10.6; I RM
      barbell squat [kg] = 129.3 +/- 17.4) participated as subjects in two randomly
      ordered sessions. During the lifting session, serum samples were collected pre-
      and 5 min post-exercise, and later analyzed for testosterone (Tes), cortisol
      (Cort), their ratio (Tes/Cort), and lactate (HLa). The lifting protocol was 10 x
      5 speed squats at 70% of system mass (1 RM +/- BW) with 2 min inter-set rest
      intervals. Mean power and velocity were determined for each repetition using an
      external dynamometer. On the control day, the procedures and times (1600-1900
      hrs) were identical except the subjects did not lift. Tes and Cort were analyzed
      via EIA. Mean +/- SD power and velocity was 1377.1 +/- 9.6 W and 0.79 +/- 0.01 m
      .s-1 respectively for all repetitions, and did not decrease over the 10 sets (p <
      0.05). Although not significant, post-exercise Tes exhibited a very large effect
      size (nmol x L-1 pre = 12.5 +/- 2.9, post = 20.0 +/- 3.9; Cohen's D = 1.27). No
      changes were observed for either Cort or the Tes/Cort ratio. HLa significantly
      increased post-exercise (mmol x L-1 ; pre = 1.00 +/- 0.09, post = 4.85 +/- 1.10).
      The exercise protocol resulted in no significant changes in Tes, Cort or the
      Tes/Cort ratio, although the Cohen's D value indicates a very large effect size
      for the Tes response. The acute increase for Tes is in agreement with previous
      reports that high power activities can elicit a Tes response. High power
      resistance exercise protocols such as the one used in the present study produce
      acute increases of Tes. These results indicate that high power resistance
      exercise can contribute to an anabolic hormonal response with this type of
      training, and may partially explain the muscle hypertrophy observed in athletes
      who routinely employ high power resistance exercise.

PMID- 20803957
TI  - [Morphofunctional distinctions of young rovers with high level of blood
      (arterial) pressure].
AB  - We've studied morphofunctional peculiarities of 47 young sportsmen-rovers. 25.6%
      of the young sportsmen suffered from the 1st degree arterial hypertension and
      8.5% had high--normal blood pressure. Profound clinical and dynamic checkup
      proved that in the group of rovers with high blood pressure the indices of
      arterial blood pressure compared to those of the group of sportsmen having normal
      blood pressure there is certain enlargement of ventriculus sinister cordis
      myocardium mass and deterioration of functional reserve.

PMID- 20803958
TI  - [Participation of growth hormone and insulin in the regulation of gastric
      secretion in athletes wrestler in sportive and post sportive ontogenesis].
AB  - The role of gastrin, STH, insulin and glucose in the formation, and long-term
      adaptation of gastric secretion in athletes--wrestlers in the sportive and post
      sportive ontogeny Revealed an undulation in the age dynamics of the basal
      secretion of hormones and glucose in the blood. The ups and downs of different
      waves in the dynamics occur in sensitive periods of ontogeny. In a bicycle stress
      load changes in the secretion of hormones and glucose levels in 90% of cases are
      not statistically significant, but insufficient to achieve the end result of
      regulation--an adequate level of hydrolysis of proteins in response to physical
      stress.

PMID- 20803959
TI  - [Investigation of mineral density and the bone structure following 105 day
      experiment in an isolated environment (MARS-105)].
AB  - Healthy volunteers' bone system investigation was performed before and after 105
      days experiment in an isolated environment (MARS-105) using dual energy X-ray
      absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT).
      Volumetric bone mineral density (VBMD), bone mineral density (BMD), structural
      parameters of radius and tibia were evaluated. There were no significant BMD
      changes revealed in skeletal parts critical in terms of biomechanical properties.
      pQCT examination noted microarchitecture deterioration of radius that was
      reflected in decreasing of trabecular number and increasing of bone tissue
      inhomogeneity. Decreasing VBMD both cortical and trabecular bone were revealed
      for tibia. Unexpectedly, increasing oftrabecular number and decreasing of
      inhomogeneity were revealed for tibia. Experiment showed that only the complex
      investigation including DXA and pQCT measurements gives an idea about bone system
      changes under simulated experiment conditions.

PMID- 20803960
TI  - [Hemostasis system indices after short-term space flights and during 7-day "dry"
      immersion experiment].
AB  - The present paper deals with studying ofhemostasis system indices after short
      term (10-11 days) space flights as well as in the course of the experiment with a
      7-day "dry" immersion. The following values were determined: activated partial
      thromboplastin time, prothrombin time, prothrombin index, international
      normalized ratio (INR), thrombin time (TT); fibrinogen, soluble fibrin-monomer
      complexes, D-dimer, plasminogen (PG) concentration; activity of antithrombin III
      (ATIII), protein C (PC), alpha2-antiplasmin (AP). In the 1st day after space
      flights a fibrinogen concentration was increased significantly as well as TT
      shortening tendency and fibrinolysis activation tendency were observed. There
      were no significant changes in ATI I11 and PC activities. During the immersion
      period there were no significant changes in investigated indices, with the
      exception of AP activity increase in 3rd day of experiment. In readaptation
      period, however, a decrease in ATIII and PC activities as well as PG
      concentration was observed. Hemostasis system response features after space
      flights and during immersion are probably due to different intensity and duration
      of external factors effects.

PMID- 20803961
TI  - [Electrical stimulation of breathing].
AB  - We have generalized data on different breathing electrostimulation methods and
      have shown their merits and demerits. We have presented electrostimulation
      methods, the electrostimulators description, different variants of electrodes
      site, parameters influence. It has shown advantages breathing electrostimulation
      application in a medical practice.

PMID- 20803962
TI  - [Diagnosis and treatment of subcortical vascular dementia].
AB  - Subcortical vascular dementia (SVD) exhibits relatively uniform clinical and
      pathological features among various subtypes of vascular dementia, and
      constitutes approximately half of vascular dementia in Japan. This subtype is
      further classified into Binswanger's type infarction and multiple lacunar
      infarctions. The former is characterized by diffuse white matter lesions, and the
      latter by lacunar infarctions. However, the both have common pathologic mechanism
      related to hypertensive small vessel changes. This paper overview the notion,
      clinical features, pathogenesis and treatment for SVD, and also refer to the
      recent topics related to Alzheimer's disease.

PMID- 20803963
TI  - [TCD monitoring during intravenous administration of recombinant tissue
      plasminogen activator].
AB  - Our aim is to investigate the utility of transcranial Doppler (TCD) monitoring
      during intravenous administration of 0.6 mg/kg recombinant tissue plasminogen
      activator (IV rt-PA) which is governmental approved in Japan. Acute ischemic
      stroke patients with M1 portion of the middle cerebral artery (M1) occlusion
      treated with IV rt-PA were prospectively enrolled. M1 occlusion was diagnosed
      before IV rt-PA using magnetic resonance angiography (MRA). Patients without
      sufficient temporal window of TCD were excluded. TCD monitoring was conducted for
      1 hour (h) during IV rt-PA. Recanalization on TCD was defined using thrombolysis
      in brain ischemia (TIBI) flow grades. After all patients were classified into two
      groups according to the presence of TCD recanalization (TCD recanalization and
      TCD non-recanalization group), three-month patients outcome, recanalization rate
      on MRA 1 h of IV rt-PA, and symptomatic cerebral hemorrhage within 24 h were
      compared between two groups. We enrolled 16 patients. Eight patients (50%, 7 men
      [88%]; age, 70 years [interquartile range. 55-81]; NIHSS score, 18 [12-22]) were
      in the TCD recanalization group and 8 (50%, 6 men [75%]; age, 72 years [62-79];
      NIHSS score 19 [15-23] were in the TCD non-recanalization group. Symptomatic
      cerebral hemorrhage was not seen in both groups at all. MRA 1 h of IV rt-PA
      revealed recanalization in all 8 (100%) patients with TCD recanalization group
      and 2 (25%) with TCD non-recanalization group (agreement, 88%; and kappa value,
      0.75, P = 0.002). At three months, 5 (63%) of 8 patients in the TCD
      recanalization group had favorable outcome, and 0 (0%) of 8 in the TCD non
      recanalization group (P = 0.026). TCD monitoring for 1 h during IV rt-PA can
      diagnose the recanalization based on MRA. TCD monitoring should predict good
      clinical outcome at three months.

PMID- 20803964
TI  - [A case of lung adenocarcinoma presenting with chorea with bilateral basal
      ganglial lesions on MRI].
AB  - The patient, a 63-year-old man, experienced the subacute onset of chorea, for
      which his family doctor prescribed oral haloperidol. However, the involuntary
      movements gradually worsened, and the patient was referred and admitted. High
      signal lesions were seen in the caudate nucleus, putamen and globus pallidus
      bilaterally on MRI T2-weighted and FLAIR images. Chest CT, FDG-PET and tissue
      biopsies also revealed that the patient had lung adenocarcinoma with multiple
      lymph node metastases. The patient was diagnosed as having paraneoplastic chorea
      associated with primary lung adenocarcinoma. Antineuronal antibodies, such as
      anti-CRMP-5 and anti-Yo antibodies, were absent. The patient received steroid
      pulse therapy, oral prednisolone therapy, and concurrent radiochemotherapy.
      Chorea and high-signal lesions in the corpus striatum bilaterally on MRI improved
      quickly, and the mediastinal lymph node swelling also improved. The patient has
      been stable for 3 years since the onset of his symptoms. As the prognosis of
      paraneoplastic chorea is relatively favorable in some patients, it should be
      considered in the differential diagnosis of patients with chorea.

PMID- 20803965
TI  - [Monthly low-dose immunoglobulin infusion as a maintenance therapy for multifocal
      motor neuropathy may reduce allergic adverse effects: a case report].
AB  - A 41-year-old man with multiple motor neuropathy developed weakness of the left
      hand at the age of 35 years. The weakness gradually progressed to his right hand.
      High-dose intravenous immunoglobulin (IVIg) therapy (0.4 g/kg for 5 consecutive
      days) improved the muscle weakness in the hands but led to the development of
      generalized severe pompholyx that spread to the skin over the entire body.
      Because muscle weakness of the hands worsened several months after IVIg therapy,
      we attempted another course of IVIg therapy. However, antiallergic agents and
      oral corticosteroids did not suppress the pompholyx induced by the high-dose
      IVIg. Hence, the treatment was switched to low-dose immunoglobulin therapy (0.4
      g/kg for one day) once every month. After more than 8 months of low-dose therapy,
      only mild form of pompholyx remained and the muscle strength was maintained
      without further deterioration.

PMID- 20803966
TI  - [A case report of serial MRI findings of cerebral fat embolism].
AB  - A 16-year-old woman was admitted to our hospital because of the motorbike
      accident On admission, her consciousness was alert, and she had lower lip
      laceration and left femur open wound. Brain CT showed no abnormality, but chest
      CT revealed slight left lungs sprain and her left femur was fractured in the
      radiograph. Debridement and the art of the steel wire pulling of the left femur
      fracture part were enforced under general anesthesia about two hours coming to a
      hospital later. Her awaking from anesthetizing after the operation was delayed,
      and the consciousness level gradually decreased. Head MRI diffusion weighted
      image (DWI) after about 36 hours coming to a hospital showed diffuse high signal
      region centering on the cerebral white matter. We diagnosed her as having
      cerebral fat embolism based on clinical course and MRI findings. DWI abnormal
      signals disappeared in three weeks and the symptoms had improved gradually. It is
      thought that head MRI-DWI is useful to diagnose and evaluate the pathophysiology
      of cerebral fat embolism.

PMID- 20803967
TI  - [A case of pure motor isolated finger palsy due to cerebral infarction].
AB  - A 73-year-old man, a right-handed, has been pointed out his atrial fibrillation
      and seen a doctor regularly for varicose veins of left leg and hypertension. He
      had complaint of a sudden paralysis of his left thumb and index finger while
      drinking beer. The next day, there was no improvement and he was admitted to our
      hospital. Neurological examination revealed mild weakness of the most muscles of
      both thumb and index finger which were innervated by radial nerve, ulner nerve,
      and median nerve. But he had no any other neurological deficits including sensory
      system. A brain MRI revealed the acute-stage cerebral infarction in the right
      precentral knob. With other examinations, we diagnosed the cerebral infarction as
      cardiogenic embolism. Pure motor isolated finger palsy (PMIFP) in association
      with cerebrocortical small lesion is rare. It is probable that some cases with
      diagnosed of peripheral neuropathy was actually PMIFP from central nervous system
      disturbance.

PMID- 20803968
TI  - [An experience of administration of modafinil for excessive daytime sleepiness in
      a patient with myotonic dystorophy].
AB  - We report the beneficial and adverse effects of modafinil for daytime sleepiness
      in a 62-year-old female patient with myotonic dystrophy. Although it was
      effective for excessive daytime sleepiness, orolingual dyskinesia appeared the
      day following administration of modafinil (100 mg/day), and dyskinesia disturbed
      her daily life including dental treatment. When modafinil was stopped, dyskinesia
      was improved. However, excessive daytime sleepiness deteriorated gradually; re
      treatment with smaller dosage (50 mg every other day) resulted in partial
      improvement but aggravation of both dyskinesia and diabetes mellitus. Modafinil
      should be administered carefully when the patient is older or has complications
      such as glucose intolerance.

PMID- 20803969
TI  - [A case of acute cerebellar ataxia associated with serum anti-NH2 terminal of
      alpha-enolase (NAE) antibody].
AB  - We reported a 61-year-old man who had developed acute cerebellar ataxia in the
      trunk and the lower limbs. His chemical blood analysis showed very mild
      hypothyroidism and the presence of serum anti-thyroid peroxidase (TPO) antibody
      and anti-NH2 terminal of alpha-enolase (NAE) antibody. While cerebellar atrophy
      was not evident on magnetic resonance imaging (MRI) of the brain, 99mTc-ECD SPECT
      using the easy Z-score imaging system (eZIS) showed decreased regional cerebral
      blood flow (rCBF) in the vermis of cerebellum. His cerebellar ataxia improved
      spontaneously within three weeks. The present case is very rare and suggests that
      anti-NAE autoantibody may be associated with actue cerebellar ataxia.

PMID- 20803970
TI  - [Anti-NMDA receptor antibody encephalitis with recurrent optic neuritis and
      epilepsy].
AB  - A previously healthy, 10-year-old girl developed left optic neuritis that treated
      with oral prednisolon (PSL). During the following 8 months, the patient exhibited
      right optic neuritis 3 days after discontinuation of PSL therapy and three
      episodes of epileptic seizures 3 weeks after PSL withdrawal Cerebrospinal fluid
      (CSF) examination revealed pleocytosis (mononuclear cells), increased IgG index,
      and positive oligoclonal IgG expression. Brain MRI showed multiple cortical,
      subcortical, and leptomeningeal enhanced lesions. However, spinal cord MRI
      revealed no lesions. Neither autoantibodies to nuclear, thyroid, alpha-enolase,
      glutamic acid decarboxylase, nor aquaporin 4 was detected. However, anti-NMDA
      receptor antibodies (NMDAR-Ab) were present in her CSF. This patient is the
      second reported case of NMDAR-related encephalitis with recurrent optic neuritis.
      The possibility of seronegative neuromyelitis optica (NMO) could not be ruled out
      for the symptom of recurrent optic neuritis. However, the presence of NMDAR-Ab in
      the CSF together with increased IgG index and oligoclonal IgG bands, which are
      usually negative in NMO suggested that this patient is NMDAR-related encephalitis
      combined with rare symptom of optic neuritis for this type of encephalitis,
      though we need to wait larger number of patients' accumulation to conclude that
      the optic neuritis could be one of the features of NMDAR-related encephalitis.

PMID- 20803971
TI  - [Pulmonary arterial hypertension and chronic thromboembolic pulmonary
      hypertension].
AB  - The Ministry of Health, Labour and Welfare (Japan) has approved research into
      primary pulmonary hypertension (PPH) and pulmonary hypertension due to chronic
      thromboembolic and/or embolic disease (CTE-PH) to examine their epidemiology,
      pathophysiology, and develop new therapeutic strategies. The Respiratory Failure
      Research Group, with grant support from the Ministry of Health, Labour and
      Welfare, changed the diagnostic names of PPH and CTE-PH. The Specific Diseases
      Control Division in the Health Service Bureau of the Ministry of Health, Labour
      and Welfare supported our proposal. One of the major purposes of The Respiratory
      Failure Research Group has been to maintain and, if possible, promote patient
      quality of life and prognosis in cases of intractable respiratory diseases. The
      name PPH has been changed to "pulmonary arterial hypertension (PAH)", and the
      name CTE-PH has been changed to "chronic thromboembolic pulmonary hypertension
      (CTEPH)", in keeping with recent worldwide research progress in this field. PAH
      should be subdivided into different pathophysiologic conditions, such as
      idiopathic and hereditary PAH, PAH associated with connective tissue diseases,
      portal hypertension, congenital heart disease, persistent pulmonary hypertension
      in newborn babies, pulmonary veno-occlusive disease etc. Different therapeutic
      strategies may be adopted for different subgroups. Pulmonary hypertension due to
      left heart disease, lung disease and/or hypoxia and CTEPH should be excluded from
      PAH. Continuous monitoring of PAH and CTEPH is required in patients with these
      conditions, even if the degree of pulmonary hypertension is improved by
      therapeutic intervention, because these diseases are incurable.

PMID- 20803972
TI  - [Questionnaire polls on health awareness of second-hand smoking exposure among
      non- and ex-smoker school teachers].
AB  - An accurate education of the harmful health effects of second-hand smoke on young
      people is important, and school teachers play a critical role. We polled school
      teachers about health awareness of second-hand smoking and the effectiveness of 4
      methods of protecting against second-hand smoke. Self-reporting questionnaires
      were given to 452 non-smoker and ex-smoker subjects. To evaluate social nicotine
      dependence, we used the Kano Test for Social Nicotine Dependence (KTSND)
      questionnaire. Of 364 teachers (80.5%) who answered and were at risk of second
      hand smoke exposure, 39.6% had respiratory symptoms, and 34.9% answered "ignore"
      or "slightly anxious" about second-hand smoking. The mean KTSND scores of those
      who answered "extremely anxious", "moderately anxious", "slightly anxious", and
      "ignore second-hand smoking" were 10.5 +/- 5.7, 12.3 +/- 6.0, 14.7 +/- 5.8, and
      18.4 +/- 4.9, respectively. The KTSND scores of teachers who answered "ignore
      second-hand smoke" were higher than those of teachers who answered "anxious". The
      scores were also higher in subjects who believe second-hand smoke can be avoided
      by the recommended protective measures, than in subjects who know that avoidance
      is impossible, indicating that these teachers accepted smoking behavior. These
      results suggest that non-smoking and ex-smoking teachers with high KTSND scores
      might underestimate the health hazards of second-hand smoke, and overestimate the
      recommended protective measures. Therefore, re-education about awareness of the
      harmful effects of second-hand smoke should be given to them.

PMID- 20803973
TI  - ['Lung age' predicts post-operative complications and survival in lung cancer
      patients].
AB  - The Japanese Respiratory Society (JRS) recently proposed 'lung age' as an easily
      understood concept of respiratory function. In this study, we evaluated whether
      'lung age' could be a useful predictor of post-operative respiratory
      complications and survival patients with lung cancer treated surgically. The
      study recruited 308 patients who underwent surgery for primary non-small cell
      lung cancer. All patients had pre-operative pulmonary function testing. 'Lung
      age' was determined using the methods advocated by the JRS. Based on the
      difference between real age' (R) and 'lung age' (L), patients were classified
      into five groups: group A: R-L > 15 (n = 37), B: 5 < R-L < or = 15 (n = 50), C: 
      5 < or = R-L < or = 5 (n = 73), D: -15 < or = R-L < -5 (n = 54), E: -15 > R-L (n
      = 94). Clinicopathological factors, post-operative respiratory complications and
      survival were compared between the groups. Gender, smoking status and index,
      histology, operative approach and FEV1 were significantly associated with the
      group classification. The incidence of complications was significantly higher in
      group E compared with other groups (p < 0.01). Multivariate analysis showed that
      the group classification by 'lung age' was an independent predictor of
      postoperative respiratory complications (p = 0.02). Overall survival differed
      significantly between the groups (p = 0.03). 'Lung age' could be useful for the
      prediction of post-operative respiratory complications and survival in patients
      with lung cancer treated surgically.

PMID- 20803974
TI  - [A case of pulmonary alveolar proteinosis which initially deteriorated rapidly
      with exacerbation of pulmonary nocardiosis, responded promptly to treatment of
      the pulmonary nocardiosis].
AB  - A 37-year-old man was admitted with complaints of continuous cough and sputum
      production for 1 month. Computed tomography (CT) of the chest revealed a solitary
      mass with a cavity in the apex of the left lung and bilateral ground-glass
      opacities (GGO). Thereafter, the patient complained of fever, and an increase in
      the mass shadow size and expansion of the ground-glass opacities were observed on
      serial CT. The patient was given diagnoses of pulmonary nocardiosis and pulmonary
      alveolar proteinosis by bronchoscopic examination. Serum anti-GM-CSF antibody
      tests were positive. On the basis of these findings, we diagnosed autoimmune
      pulmonary alveolar proteinosis. After beginning antituberculosis drugs and
      antibiotics, the tumor shadow and GGO reduced. The pulmonary alveolar proteinosis
      rapidly worsened on exacerbation of the pulmonary nocardiosis, but prompt overall
      improvement was obtained after treating the latter. We believe this to be a
      valuable case for examining the time progression of autoimmune pulmonary alveolar
      protein syndrome, because of the clinical course of the exacerbation, and the
      improvement in the pulmonary alveolar proteinosis after treatment of pulmonary
      nocardiosis.

PMID- 20803975
TI  - [A case of radiation-related pneumonia and bilateral tension pneumothorax after
      extended thymectomy and adjuvant radiation for thymoma with myasthenia gravis].
AB  - A 62-year-old man was admitted to our hospital with a 2-month history of
      progressive cough and dyspnea. He had undergone thymectomy for thymoma with
      myasthenia gravis. Adjuvant radiation of 50 Gy had been performed until 6 months
      before the symptoms developed. Chest computed tomography showed infiltrative
      findings even outside the irradiated area. We diagnosed radiation-related
      pneumonia, and 30 mg per day prednisolone was initiated. On the final day, he
      developed bilateral tension pneumothorax. After chest tube drainage, the right S5
      bulla was resected with video-assisted thoracoscopic surgery (VATS). The right
      pneumothorax caused the bilateral tension pneumothorax, because the right and
      left thoracic cavity communicated in the anterior mediastinum after thymectomy.
      We should be aware of the risk of bilateral tension pneumothorax following
      radiation-related pneumonia after extended thymectomy and adjuvant radiation in
      patients with myasthenia gravis.

PMID- 20803976
TI  - [A case of sarcoidosis with an endobronchial polypoid lesion].
AB  - A 59-year-old woman complained of impaired vision. She visited an ophthalmologist
      and glaucoma was diagnosed. In July 200X, she was admitted to our hospital for
      further examination. Chest radiography and CT showed lymphadenopathy in the
      mediastinum and bilateral hilum. Bronchofiberscopy revealed mucosal
      hypervascularity and a polypoid lesion at the orifice of the left B8a. A
      transbronchial biopsy specimen of the polypoid lesion showed non-caseating
      epithelioid cell granuloma. On bronchoalveolar lavage, both the proportion of
      lymphocytes and the CD 4/8 ratio had increased. We diagnosed sarcoidosis with an
      endobronchial polypoid lesion. The patient has been observed without therapy
      since, and after a year the polypoid lesion is the same size on 3D CT scans. This
      is a very rare case of endobronchial sarcoidosis presenting as a polypoid lesion.

PMID- 20803977
TI  - [A pulmonary tumor embolism which mimicked pulmonary tumor thrombotic
      microangiopathy caused by uterine cervical cancer].
AB  - A 58-year-old woman presented with cough and dyspnea on exertion. A chest CT scan
      showed infiltrative cuneiform shadows in the peripheral lung fields. Pulmonary
      perfusion scintigraphy showed multiple nonsegmental defects. Histological
      analysis of the transbronchial lung biopsy specimens obtained from the right
      lower lobe showed tumor cell embolism and fibrocellular intimal proliferation,
      but no thrombus formation or recanalization in the small arteries. On the basis
      of these findings, we diagnosed pulmonary tumor embolism, not pulmonary tumor
      thrombotic microangiopathy (PTTM), because the pathological findings did not
      reveal either thrombus formation or recanalization, and the patient did not show
      hemodynamic effects such as hemolytic anemia, severe pulmonary hypertension, or
      disseminated intravascular coagulation. Systemic examinations revealed uterine
      cervical cancer. Her symptoms improved after the administration of chemotherapy
      and radiation therapy. Furthermore, the multiple nonsegmental defects observed on
      pulmonary perfusion scintigraphy disappeared. She was discharged, and her uterine
      cervical cancer has not recurred to date. Generally, a diagnosis of pulmonary
      tumor embolism and PTTM is difficult to establish in living patients. It is
      important that therapy is started before the disease progresses to PTTM, if
      pulmonary tumor embolism is diagnosed.

PMID- 20803978
TI  - [A case of advanced adenocarcinoma of the lung which maintained complete response
      for 5 years by treatment with gefitinib].
AB  - A 73-year-old woman smoker presented with dyspnea on exertion due to massive left
      pleural effusion. A CT scan after drainage of the pleural effusion demonstrated a
      nodule in the left lung, and cytology of the pleural effusion showed
      adenocarcinoma. We diagnosed advanced adenocarcinoma of the lung, and clinical
      stage IIIB. Chemotherapy with carboplatin and docetaxel was discontinued after
      the second course because of anorexia, and gefitinib was administered from
      October 2004. The lung nodule and pleural effusion had disappeared on CT by
      November 2004. A complete response continued for 5 years. We report a 5-year
      complete response in a case of advanced adenocarcinoma of the lung by treatment
      with gefitinib.

PMID- 20803979
TI  - [Twelve cases of advanced thymic carcinoma: a clinical review].
AB  - Thymic carcinoma is comparatively rare and no standard treatment has been
      established for advanced stage cases. We reviewed our therapeutic experience in
      12 cases of thymic carcinoma. They consisted of 9 men and 3 women, ranging from
      38 to 69 years of age, with a mean age of 56.5. According to Masaoka's
      classification, 5 cases were stage III and 7 were preoperative stage IVb. Nine
      cases were squamous cell carcinoma and 3 were adenocarcinoma. Four cases of
      preoperative clinical stage III underwent extended thymectomy, but none were
      completely resected and were classified as stage IV postoperatively. Chemotherapy
      combined with radiation therapy was given in 1 case, chemotherapy (monotherapy)
      was given in 4 cases, radiation therapy was given in 1 case, and 2 cases received
      best supportive care. The median survival time (MST) of patients who had
      undergone combined modality treatments including surgery was 1971 days, which was
      longer than the MST of 567 days of patients who were not able to undergo surgery.
      The prognosis outcome of advanced thymic carcinoma is poor, but combined modality
      therapies such as surgery, chemotherapy and radiation can be effective for some
      advanced thymic carcinoma cases.

PMID- 20803981
TI  - [A case of early-onset pulmonary emphysema suspected to be hereditary].
AB  - A Japanese woman who developed dyspnea on effort and systemic edema at the age of
      21 died of respiratory failure at age 33. She had no smoking history, air
      pollution exposure, or alpha 1-antitrypsin deficiency. Her father had also died
      of respiratory failure at the age of 30. This disorder was suspected to be
      hereditary.

PMID- 20803980
TI  - [Pulmonary non-tuberculous mycobacteriosis (Mycobacterium intracellulare) with
      cavities developing in a non-small cell lung cancer patient during chemotherapy].
AB  - A 70-year-old man was admitted to our hospital for examination of an abnormal
      shadow found on a chest radiograph. Chest CT showed a nodular shadow in the left
      upper lobe S1+2. We diagnosed non-small cell lung cancer (squamous cell
      carcinoma) clinical stage T4N2M1. Chemotherapy consisting of carboplatin and
      weekly paclitaxel was begun. After the second course of chemotherapy, another
      nodular shadow with small cavities in the left lower lobe S6 was seen, and which
      then increased in size. Bronchial lavage revealed a diagnosis of non-tubercular
      mycobacteriosis (Mycobacterium intracellulare). Anti-NTM chemotherapy consisting
      of rifampicin, ethambutol and clarithromycin was started in addition to
      anticancer chemotherapy, without severe side effects. Although there are some
      reports of the co-occurrence of lung cancer and non-tuberculous mycobacteriosis,
      this apparently rare case involved the appearance of a solitary nodule with a
      cavity caused by pulmonary non-tuberculous mycobacteriosis during anticancer
      chemotherapy.

PMID- 20803982
TI  - [A case of drug-induced pneumonitis due to a cold remedy].
AB  - The patient was an 84-year-old woman who took a combination cold remedy, Shin
      Rulu-A' for three days because of fever and cough. However, her symptoms worsened
      and she visited our hospital. Arterial blood gas analysis revealed severe
      hypoxemia and chest computed tomography showed diffuse ground glass opacities in
      both lungs. Analysis of bronchoalveolar lavage fluid disclosed an increased
      proportion of lymphocytes. The cold remedy was stopped, corticosteroids were
      administered, and she recovered. After positive results of lymphocyte stimulation
      testing to Shin-Rulu-A, a diagnosis of drug-induced pneumonitis was made. However
      the responsible ingredient was not established, because lymphocyte stimulation
      tests for each ingredient in Shin-Rulu-A were negative. To the best of our
      knowledge, this is the second report of Shin-Rulu-A-induced pneumonitis in Japan.

PMID- 20803983
TI  - [A case of resected pulmonary mucormycosis that was suspected of mixed infection
      with Aspergillus fumigatus, diagnosed by transbronchial lung biopsy].
AB  - A 73-year-old man was admitted with high fever and right chest pain. Chest X-ray
      showed a rapidly growing mass shadow in the right lower lung field. The patient
      had been in remission for malignant lymphoma and had developed interstitial
      pneumonia and diabetes mellitus following 1 year of corticosteroid therapy. His
      illness was diagnosed as invasive aspergillosis because of a high level of beta-D
      glucan and cultured Aspergillus fumigatus in the sputum. He was treated with a
      combination of micafungin and itraconazole. However, because these agents did not
      improve his clinical condition, transbronchial lung biopsy was performed.
      Histologically, Mucor hyphae were detected in these specimens. Micafungin and
      itraconazole were stopped and infusion of liposomal amphotericin B was initiated.
      Because his condition worsened, a right lower lobectomy was performed. Rhizopus
      Oryzae was detected in the lung tissue. We report a case of pulmonary
      mucormycosis in which mixed infection with A. fumigatus was suspected. Pulmonary
      mucormycosis is a life-threatening infection in which it is rare that an
      antemortem diagnosis is established and organisms are isolated. We believe
      diagnostic tests should be performed aggressively, even when pulmonary
      aspergillosis is suspected.

PMID- 20803985
TI  - [Validity, usefulness and difficulties of the diagnosis of sarcoidosis by new
      diagnostic criteria and guidelines for sarcoidosis].

PMID- 20803984
TI  - [A case of relapsing sarcoidosis with pleurisy 14 years after spontaneous
      remission].
AB  - An 83-year-old woman was referred to our hospital with dyspnea on exertion and
      right pleural effusion. At the age of 69, she had been given a clinical diagnosis
      of sarcoidosis due to uveitis, bilateral hilar lymphadenopathy, bilateral
      multiple nodular shadows on chest images, and serum angiotensin-converting enzyme
      (SACE) level elevation. Remission was spontaneous. The pleural effusion was
      exudative lymphocyte-rich. On thoracoscopy, the macroscopic appearance of the
      parietal pleura was telangiectasia without nodular lesions and the pleural biopsy
      specimens revealed non-caseating epitheloid cell granulomas whose cultures were
      negative for acid-fast bacilli and fungi. A tuberculin skin test and QFT-2G were
      negative, thus we diagnosed sarcoidsis pleurisy.

PMID- 20803987
TI  - [Evaluation of revised diagnosis criteria for sarcoidosis].
AB  - PURPOSE: Based on diagnostic criteria revised in 2006, we investigate whether a
      simple examination will provide a diagnosis for uveitis of sarcoidosis. SUBJECTS
      AND METHODS: Two hundred and six patients with uveitis suspected of having
      sarcoidosis who visited 4 hospitals from 1978 to 2008 were evaluated according to
      Their ocular and systemic findings. RESULTS: One hundred and six patients were
      diagnosed as having sarcoidosis. Most patients had more than 4 ocular criteria.
      Bilateral hilar lymphadenopathy (BHL) was seen in 103 (97.2%) of the patients.
      When BHL was not detected with conventional chest X-rays, chest computerized
      tomography (CT) was useful in detecting BHL, especially in patients who were
      tuberculin negative. CONCLUSIONS: When sarcoidosis is suspected from ocular
      findings, chest X-rays, a tuberculin skin test and serum angiotensin converting
      enzyme should be performed first. Even if BHL is not detected, a chest CT is
      useful in cases that are tuberculin negative.

PMID- 20803986
TI  - [Effect of anti-glaucoma drugs on inflammatory cytokine production by human and
      murine peripheral blood mononuclear cells].
AB  - OBJECTIVE: We investigated both human and murine peripheral blood mononuclear
      cells to find which of the anti-glaucoma drugs used to lower intraocular pressure
      drug also suppresses inflammation. SUBJECTS & METHODS: Peripheral blood
      mononuclear cells (PBMCs) prepared from healthy men and from BALB/c mice were
      suspended in RPMI 1640 culture medium containing 10% FBS. Each test drug was
      added to the cells, and they were cultured in a CO2 incubator (set to 37 degrees
      C and 5% CO2) for 30 minutes. Lipopolysaccharide (LPS) was added to the same
      cells and they were cultured again for a given period of time, after which either
      tumor necrosis factor-alpha (TNF-alpha) or interleukin-6 (IL-6) levels in the
      culture medium were determined by ELISA. RESULTS: Carteolol inhibited production
      of both TNF-alpha and IL-6 from PBMCs. The other test agents had no inhibitory
      effect. The carbonic anhydrase inhibitor (CAI) dorzolamide, isopropyl unoprostone
      and latanoprost had almost no effect on the production of inflammatory cytokines.
      CONCLUSIONS: We demonstrated that carteolol exhibits an inhibitory action on the
      production of inflammatory cytokines from PBMCs because of its intrinsic
      sympathomimetic action. We also showed that CAI and PG drugs had almost no effect
      on inflammatory cytokine production.

PMID- 20803988
TI  - [Rifabutin-associated hypopyon uveitis in patient with acquired immunodeficiency
      syndrome].
AB  - BACKGROUND: Rifabutin-associated uveitis has been recognized and established
      overseas, but there have been no reports of its occurance in Japan. We report a
      case of rifabutin-induced hypopyon uveitis in a patient with acquired
      immunodeficiency syndrome (AIDS). CASE: A 45-year-old Filipino man with AIDS and
      pulmonary tuberculosis was on highly active antiretroviral therapy (HAART;
      lopinavir/ritonavir, zidovudine/lamivudine) and anti-tuberculosis therapy
      (isoniazid, rifabutin). At 11 weeks after starting rifabutin administration,
      unilateral acute uveitis with hypopyon developed, which progressed to bilateral
      uveitis by the following day. Funduscopic examination revealed no vitreo-retinal
      abnormalities. The uveitis resolved after discontinuation of the rifabutin and
      initiating topical corticosteroids and mydriatic therapy. No recurrence of the
      uveitis was noted during a 5-month follow-up period. CONCLUSION: Rifabutin
      associated uveitis with hypopyon should be considered as one possible causes of
      uveitis.

PMID- 20803990
TI  - [Guideline for refractive surgery. Committee on Refractive Surgery, Japanese
      Society of Ophthalmology].

PMID- 20803989
TI  - [A case of hypertrophic pachymeningitis impeding differential diagnosis of
      mycosis of orbital apex syndrome].
AB  - PURPOSE: Mycosis of the orbital apex is often fatal. We report case of orbital
      apex syndrome, which appeared to have been caused by hypertrophic pachymeningitis
      with positive systemic mycosis antigens treated with systemic corticosteroid
      combined with antimicrobiotic therapy. CASE: A 57-year-old woman presented with
      disturbed ocular motility and visual disturbance of her left eye. She had
      rheumatoid arthritis. Magnetic resonance imaging(MRI) showed an abnormal blush in
      the left orbital apex and meningeal thickening in the cranial base, leading to
      the diagnosis of hypertrophic pachymeningitis. She also had candidemia. Systemic
      corticosteroids combined with antimicrobiotic therapy resulted in improved
      clinical ocular manifestations. She died 13 months later due to interstitial
      pneumonia. CONCLUSION: The diagnosis of this case was difficult because of the
      candidemia. But the effective steroid response indicates that the probable cause
      was hypertrophic pachymeningitis due to RA. To avoid complications, hypertrophic
      pachymeningitis associated with fungemia should be treated with corticosteroids
      combined with antimicrobiotic therapy.

PMID- 20803991
TI  - [Dose loads on and radiation risk values for cosmonauts on a mission to Mars
      estimated from actual Martian vehicle engineering development].
AB  - The current design philosophy of a Mars orbiting vehicle, takeoff and landing
      systems and the transport return vehicle was taken into consideration for
      calculating the equivalent doses imparted to cosmonaut's organs and tissues by
      galactic cosmic rays, solar rays and the Earth's radiation belts, values of the
      total radiation risk over the lifespan following the mission and over the whole
      career period, and possible shortening of life expectancy. There are a number of
      uncertainties that should be evaluated, and radiation limits specified before
      setting off to Mars.

PMID- 20803992
TI  - [Indralin--a novel effective radioprotector during irradiation by high-energy
      protons].
AB  - Experiments with 120 mongrel dogs were aimed at the assessment of radio
      protective strength of indralin and local shielding of the pelvic marrow from 2.5
      Gy, and also their concurrent use for the dogs irradiated by protons (240 MeV) at
      absolutely lethal and over-lethal 4 Gy and 5 Gy. Clinical observations,
      hematological investigations and ECG analysis of survived animals were conducted
      4.5 years post the irradiation. Dogs that remained healthy following 3.5 to 4.5
      years since the irradiation were sacrificed for pathomorphological
      investigations. The radioprotective effect of local shielding against 4 Gy was
      weak while this effect of intramuscular indralin (10, 20, 40 mg/kg of body) was
      significant reaching 50 to 67.7%. The concurrent use of two methods had,
      apparently, potentiated the 100% radioprotection of the animals irradiated by
      overlethal 5 Gy. Blood investigations of the survived dogs every 2-4 months
      evidenced that complete recovery of the total leukocyte count had taken 9 to 13
      months. Also, dogs' pregnancy in 9-10 months since the beginning of irradiation
      pointed to maintenance of fertility and the ability to parturiate 2 or 3 times
      yielding 5-6 live cubs. Necropsy of the dogs did not reveal gross macroscopic
      structural changes of visceral organs or tissues. Seven out of 27 sacrificed dogs
      had benign tumors infrequent in intact dogs at this age.

PMID- 20803993
TI  - [Some of the aspects of comparative analysis of the hemodynamic reactions to LBNP
      in cosmonauts of different age groups].
AB  - This was the first study of age-related differences of the cardiovascular system
      functioning and reactions to the LBNP test in career cosmonauts. Results of 174
      LBNP tests performed within the standard medical monitoring program using Gamma
      01 (orbital station Mir) and Gamma-lM (ISS) were subjected to comparative
      analysis. Thirty eight cosmonauts--members of 25 long-duration Mir and ISS
      missions were divided into two age groups, i.e. 30-39 y.o. (mean 36 & 0.7, 39% of
      all subjects) and 40-55 y.o. (mean 46 & 0.8, 61% of all subjects). The testing
      was performed before launch and in flight (typically on FD-120). Age-specifc
      changes in the hemodynamic status were recorded in resting cosmonauts pre-flight
      and in spaceflight microgravity; relative dynamics of the CV parameters in
      response to standing posture imitation was on one and the same patterns and yet
      demonstrated unequal intensity before and in flight. Test results implicate that
      analysis and interpretation of cosmonauts' medical monitoring data should take
      into account individual age, which is of particular practical importance when
      dealing with the LBNP test data obtained in different periods of space flight.

PMID- 20803994
TI  - [Influence of pilot's professional activity on the adaptive character of
      hemodynamic reactions to the tilt test].
AB  - The comparative study of blood circulation reaction to the tilt test was
      performed with three groups of essentially healthy subjects: AF pilots (n = 72),
      locomen (n = 44) and students of Military Institute of Radio Electronics (n =
      32). In each group, adequate adaptive reactions were due to the eukinetic
      hemodynamics with steady minute volume and blood pressure values combined with
      heart rate increase by 10-12%. Hypokinetic hemodynamics caused 20% growth in
      minute volume during the initial 5 minutes of tilting in pilots versus 8-12%
      growth in non-flyers. Hyperkinetic hemodynamics was responsible for the minute
      volume growth in pilots but not in the other groups of subjects. Parasympathetic
      system activation was peculiar of hypokinetic hemodynamics, while sympathetic
      system activation was associated with hyperkinetic hemodynamics. These results
      point to a larger body functional reserve in pilots compared with the other
      subjects as a by-effect of the profession.

PMID- 20803995
TI  - [Effect of 7-day dry immersion on the mechanisms of ocular saccadic movements
      generation].
AB  - To evaluate the impact of prolonged support deprivation on the mechanisms of
      ocular saccadic movement generation, four volunteers were tested on the eve of 7
      d dry immersion and on the completion day. The task consisted of tapping random
      light stimuli emerging on the periphery of sensory screen. During testing, the
      head was kept in a fixed position. To tap stimuli, human subject was either to
      touch a respective spot on the screen with a finger with gaze shifting and
      fixation accompanying coordinated hand movement (1) or to press the mouse key
      after gaze fixation on stimulus (2). Movements of the eyes were registered and
      analyzed in the infrared frequency of 200 Hz. It is maintained that the similar
      impact of immersion on the peak saccade velocity-amplitude ratio no matter how
      stimuli were tapped suggests saccade acceleration after immersion in consequence
      of the direct effect of prolonged support deprivation.

PMID- 20803996
TI  - Body-weight distribution on forelimbs in rat tail-suspension model.
AB  - To understand the tail-suspension model to simulate weightlessness better, this
      study was to investigate the relationship of the amount of body weight supported
      by forelimbs between the tilt angles of rat in the model. Normal rat had at least
      two basic postures. One was standing or walking, in which the forelimbs bear
      44.6% of the body weight; the other one was resting, in which 23.9% of body
      weight was placed on the forelimbs. As for tail-suspended rat, body-weight
      distribution on forelimbs was linearly related to tilt angle. The linear
      relationship was y = -0.7423x + 70.849, R2 = 0.9269. The tilt angle should be
      approximately 35 degrees if normal standing load of 44.6% body weight was placed
      on the forelimbs. On the other hand, it should be approximately 63 degrees if
      normal resting load of 23.9% of body weight was placed on forelimbs. Furthermore,
      the body load on forelimbs in tail-suspension model became much larger if the
      period of different postures was considered. Therefore, it should be careful if
      forelimbs are used to be as convenient internal control in tail-suspended rats.

PMID- 20803997
TI  - [The use of impulse plasma-optical ultraviolet technologies for ensuring
      microbial safety of the space station environment].
AB  - Purpose of the work was to study usability and efficiency of UV decontamination
      units aboard space station. UV-radiators were high-intensity xenon flashbulbs, as
      well as standard mercury and amalgam lamps; subjects were reference strains and
      test-microorganisms isolated from the ISS environment. Quantities of viable
      airborne and superficial microorganisms were determined before and after UV
      irradiation. The sanitary-microbiological assessment involved visual and
      microscopic counting of colony-forming units on material samples (CFU/100 cm2)
      and Petri dishes after air sampling (CFU/m3 of air). Continuous spectrum of high
      intensity pulsed UV was demonstrated to be effective against contamination both
      by vegetative and high-resistant bacterial spores and molds.

PMID- 20803998
TI  - [Examination of the antimicrobial activity of some G. Begonia L. species as a
      possible piece of phytodesign].
AB  - Antimicrobial properties of volatile emanations of intact g. Begonia plants in
      air-tight chambers and ordinary rooms were studied. The plants were effective
      against microbial test-objects Staphylococcus epidermidis, Escherichia coli and
      yeast like fungi.

PMID- 20803999
TI  - [Effectiveness evaluation of the sanitary-hygienic measures during 105-day
      isolation].
AB  - The sanitary-hygienic well-being of 6 volunteers for the 105-d chamber experiment
      simulating some of the spaceflight factors was evaluated. To evaluate the
      pertinent means and methods, clinical, hygienic and microbiological
      investigations were employed, and volunteers' subjective opinions of personal
      hygiene items and associated procedures were analyzed Based on the examination of
      integument and oral cavity, entries in the questionnaires concerning subjective
      sensations, opinions and objective data, all volunteers were invariably in good
      state. Level of the skin total microbial contamination was found to depend on
      volunteers' diligence to fulfill the hygienic routine.

PMID- 20804000
TI  - [Effect of plant-associated methanolic bacteria on methane and methanol
      concentration dynamics in atmosphere of pressurized chamber].
AB  - Stability of Chinese cabbage crop colonization by methanolic bacteria
      Methylovorus mays, Methylomonas methanica and Methylosinus trichosporium
      inoculated using a space-applicable method was evaluated. Besides, trends of
      methane and methanol concentrations in the pressurized chamber with inoculated
      and uninoculated crops were calculated. Methylovorus mays and Methylosinus
      trichosporium were shown to establish more stable colonization as compared to
      Methylomonas methanica. Also, stable association of methanolic bacteria with
      plants reduced airborne methanol 75% faster owing to its uptake by bacteria.
      Therefore, inoculation of these microorganisms can be viewed as a promising
      method of controlling volatile pollutants in space vehicle atmosphere. Methane
      drop after 6-hour exposure to inoculated control and test crops was not
      significant.

PMID- 20804002
TI  - [On the mechanism of antimotion sickness effects of mexidol].
AB  - The path-clamp method used within the whole-cell configuration in experiments
      with convoluted medullar oblongata sections obtained from white mongrel male rats
      aged 13 to 17 days evidenced that 5 mV of mexidol caused 96 +/- 2% inhibition of
      the excitation postsynaptic current in neurons of the medial vestibular nucleus
      generated by the depolarization step of 10 mV (holding potential = -70 my). This
      means that the antimotion sickness effect of mexidol has its origin in the ion
      mechanisms with involvement of the glutamate- and GABAergic components, primarily
      inhibition of ion currents through channels of the NMDA-receptor complex.

PMID- 20804001
TI  - [Changes in lipid composition of human plasma and erythrocyte membranes due to
      sodium hydroxybutyrate and normobaric hyperoxia during bed rest].
AB  - Gas chromatography was employed to study effects of sodium hydroxybutyrate (GHBA)
      and normobaric hyperoxia on the fatty-acid composition of total lipids of blood
      plasma and erythrocyte membranes in 5 normal male volunteers in the baseline data
      collection period and during 14-d bed rest. Both in plasma and erythrocyte
      membranes saturated palmitic acid was found increased and polyunsaturated
      linoleic acid and arachidonic acid reduced.

PMID- 20804003
TI  - [Medical and biological safety assessment of genetically modified soybean event
      MON 89788. Report 1. Toxicologo-hygienic examinations].
AB  - The results of toxicologo-hygienic examinations, which were conducted within the
      framework of integrated medical and biological assessment of genetically modified
      second generation soybean event MON 89788, are presented. Analysis of
      morphological, hematological, biochemical parameters and system (sensitive)
      biomarkers has not confirmed any toxic effect of soybean event MON 89788.

PMID- 20804004
TI  - [Medical and biological safety assessment of genetically modified soybean event
      MON 89788. Report 2. Genotoxicologic, immunologic and allergologic examinations].
AB  - There are presented the results of genotoxicologic, immunologic and allergologic
      examinations which were conducted within the framework of integrated medical and
      biological assessment of genetically modified second generation soybean event MON
      89788. Analysis of damages of DNA and structural chromosome aberrations,
      assessment of the allergenic potential and immunoreactive properties has not
      confirmed any genotoxic, allergenic and immunotoxic effect of soybean event MON
      89788.

PMID- 20804005
TI  - [Participation of endotoxin from gram-negative bacteria in mechanisms of
      regulation of thyroid status].
AB  - Alteration of thyroid hormone blood levels in rats in different periods after
      exposure of high dose of lipopolysaccharide from E. coli were studied. Direct
      inhibition of thyroid function without hypothalamus-pituitary dysfunction is
      revealed. High dose by high doses of bacterial endotoxin leads to changes in rat
      thyroid status caused by both hypothalamus-pituitary and thyroid hypofunction.

PMID- 20804006
TI  - [Detection of bacteria genus Campylobacter in poultry products by PCR method].
AB  - Researches on method PCR adaptation for detection Campylobacter spp. in poultry
      meat with use of two devices and kits and its comparison with a bacteriological
      method under characteristics of specificity and the bottom limit of definition
      are carried out. Higher efficiency of detection of Campylobacters to PCR in real
      time, than a bacteriological method, and also suitability for the purposes of the
      foods control of the kits intended initially for clinical diagnostics is shown.
      It is specified on necessity of a stage of bacteria enrichment before PCR up to a
      level above 10(5) CFU/g.

PMID- 20804007
TI  - [Definite of nutritional status in patients with metabolic syndrome with the use
      of modern methods of nutrimetabolomica].
AB  - A comprehensive assessment of nutritional status in 73 patients with metabolic
      syndrome was assessed. The consumption food pattern of the majority of examined
      patients have had increased energy intake with excessive fat consumption
      inadequate intake of complex carbohydrates. In patients with type 2 diabetes
      inadequate compensation of carbohydrate and lipid metabolism was marked. When
      assessing body composition method bioelectrical impedance analysis increased
      content of adipose tissue was revealed are positively correlated with insulin and
      tumor necrosis factor-alpha. According to indirect calorimetry, increase in the
      level of resting energy expenditure, reducing the rate of oxidation of fat,
      increase the rate of oxidation of protein and carbohydrates was noted.

PMID- 20804008
TI  - [Clinical significance of food antigens blotting capacity by patients with
      irritable bowel syndrome].
AB  - 53 patients suffered from IBS (according to Rome III criteria) were included to
      the study with solid-phase immune-enzyme detection of the ovalbumin blood level
      after consumption of egg whites. Patient complaints and quality of life were
      assessed. The same blood samples were tested for content of the total IgE and
      specific to food IgE (13 food allergens); specific to food IgG (24 food
      allergens). The abnormal intestinal permeability was found in 38% IBS patients,
      also the degree of abdominal pain was significantly higher and quality of life
      was lower in this patients. The abnormal intestinal permeability was found more
      frequently in IBS-C patients High levels of IgE and IgG were detected in a few
      IBS patients.

PMID- 20804009
TI  - [Estimation of anthropometric indexes for patients with anorexic nervosa and body
      mass deficiency].
AB  - New data regarding individual peculiarities of structure for patients with
      dystrophy and anorexia nervosa is presented in this article. Component structure
      of the body for patients has been studied. Constitutional predisposition and body
      structure for such patients has been defined.

PMID- 20804010
TI  - [A food and the food status of workers brainwork with low physical activity].
AB  - The data of the investigation of 340 average income men and women ages 18-60
      whose labour is characterized by low power expenditure, are represented in this
      article. Their food ration contains about 13% of protein and more than 40% of
      fat, the most part of it contains the saturated fatty acids. 55% of men and 50%
      of women have got body mass index (BMI) more than 25; obesity is revealed with 7%
      of men and 18% of women. Glucose blood level is raised at 30% of the surveyed and
      is correlated with the consumption of the added sugar (r = 0.44; p < 0.05). The
      cholesterol maintenance in blood is above normal with 60% of the surveyed,
      cholesterol connection with the cholesterol food maintenance is not revealed.

PMID- 20804011
TI  - [Nitrogenous metabolism vitamin provision and anthrometric indices by Uzbek young
      with a different nutrition status].
AB  - Nitrogenous metabolism, vitamin provision and anthroponietric indices were
      inventigated in 1560 Uzbek youths (18-21 years old) with diverse alimentary
      status. Changes cheatinine in urine, insufficient vitamines content and
      violations of authropometric indices were revald in patients with protein-calorie
      deficiency.

PMID- 20804012
TI  - [Evaluation of dietary intake of indigenous and alien populations in Yamal-Nenets
      Autonomous District].
AB  - The paper describes the investigation of the actual food consumption in 102 adult
      residents of both sexes in settlements Harp, Aksarka and Beloyarsk in Yamal
      Nenets Autonomous District - YNAD. The dietary intake of individuals were studied
      by 24-hour recall methodology adopted for Russian features in the Institute of
      Nutrition of RAMS. An assessment of differences of the actual consumption of
      energy and nutrients for newcomers and indigenous populations were performed.

PMID- 20804013
TI  - [Epidemiologic studies on nutrition role in develomeat of osteoarthrosis. Report
      1. Analysis of actual intake of nutrients and energy in depend on financial
      position and in come patients osteoarthrosis].
AB  - The study gives the characteristic of the social situation of patients with
      osteoarthrosis (OA), among which is dominated by people with disabilities and
      senior citizens (60%), most of which belongs to the poor. The actual nutrition of
      patients with OA is characterized by low energy intake and macronutrients.
      Feeding low-income patients with OA was characterized by inadequate intake of
      ascorbic acid and calcium, whereas the intake of vitamin A, E and beta-carotene
      was higher in patients with OA compared with the control group.

PMID- 20804014
TI  - [The alteration of vitamin status of adult population of the Russisn Federation
      in 1987-2009 (to the 40th anniversary of the Laboratory of Vitamins and Minerals
      of Institute of Nutrition at Russian Academy of Medical Sciences)].
AB  - Monitoring of vitamin status of various groups of adult population (by vitamin
      serum blood level evaluation) during the period since 1987 on 2009 has shown that
      an authentic improvement of sufficiency with vitamin C takes place. At the
      present time the deficiency of B group vitamins has been determined much more
      often than the deficit of vitamins C, A and E. The revealed deficiencies don't
      depend on a place of residing and a professional accessory and, as a rule, affect
      not any one vitamin, but have a character of combined insufficiency of B group
      vitamins and some other vitamins.

PMID- 20804015
TI  - [The new method for simultaneous determination of natural and synthetic food dyes
      by high performance liquid chromatography].
AB  - In the food industry in Russia is currently allowed to use more than 30 different
      dyes. Existing approaches to monitoring their use in foods are based on
      spectrophotometry, thin layer chromatography and high performance liquid
      chromatography (HPLC). Methods of research focused on the analysis of a specific
      class of food dye--natural or synthetic, and can not be used in the analysis of
      their mixtures. The aim of work was to develop HPLC method for the joint
      determination of various classes of dyes in complex food additives and food
      products. As a result of the research suggested a method to allow a simultaneous
      determination of at least 15 natural and synthetic food dyes.

PMID- 20804016
TI  - [Optimization of the sports nutrition: reality and perspectives].
AB  - The review about modern state of the Sports nutrition, as well as its
      discussional questions and developmental perspectives are observed.

PMID- 20804017
TI  - [The Gallery of National Surgeons].

PMID- 20804018
TI  - [Surgeons of Leningrad in days of blockade and years of the Great Patriotic War
      of 1941-1945].

PMID- 20804019
TI  - [Contribution of Perm scientists in the development of national surgery in the
      period of the Great Patriotic War].

PMID- 20804020
TI  - [Aneurysmatic and occlusive lesions of the aorto-iliac segment in combination
      with cancer of the lungs and organs of the abdominal cavity].
AB  - An analysis of retrospective data has shown that 34 (14.4%) out of 236 patients
      with aneurysm of the abdominal aorta and iliac arteries and in 62 (5.1%) out of
      1214 patients with occlusion or stenosis of these vessels mainly had cancer of
      the lungs (52%) and stomach (17.7%) with almost similar incidence in both groups.
      Colorectal cancer (8.3%) and cancer of other organs of the abdominal cavity were
      detected more rarely. Aneurysmatic (12 patients) and occlusive-stenosing (17
      patients) lesions of the aorto-iliac segment were noted in 29 (0.4%) among 6834
      patients with lung cancer or organs of the abdominal cavity. There were three
      subgroups of patients: (1) first cancer was diagnosed, and then aneurysm,
      stenosis or occlusion of these arteries (12-12.5%); (2) diseases of the arteries
      and cancer were diagnosed simultaneously (60-62.5%) and (3) first lesions of the
      arteries and later cancer (24-25%). Two-stage operative interventions for these
      diseases were made in 30 (31.2%) patients.

PMID- 20804021
TI  - [Postulcerorhaphic syndrome: causes of the development and pathogenetic forms].
AB  - The article deals with the question of consequences of suturing perforating
      pyloroduodenal ulcer in late terms in 355 patients. Marking out the
      postulcerorhaphic syndrome which complicated the course of the ulcer disease in
      24.5% of cases and requires the determination of early indications to reoperation
      was grounded.

PMID- 20804022
TI  - [Quality of life of patients at late terms after surgical treatment of
      complicated forms of diabetic foot syndrome].
AB  - Quality of life were explored in an open prospective controlled study in 116
      patients with complicated diabetic foot syndrome (experimental group) and 30
      diabetics without this syndrome (control group) by questioning of quality of life
      (questionnaires SF-36, Functional Scale of Lower Extremity) in long terms (6-18
      months) after surgical treatment. Advantages of foot "saving" resections in
      surgical treatment of complicated diabetic boot syndrome were detected: patients
      without amputations had the physical wellbeing score and the Functional Scale of
      Lower Extremity number, comparable with the group of diabetics without diabetic
      foot syndrome. The integral mental wellbeing scores were low in all observed
      groups of patients.

PMID- 20804023
TI  - [Minimally invasive surgery of abscesses of the retroperitoneal space].
AB  - The article presents an experience with treatment of abscesses of the
      retroperitoneal space in 28 patients using interventions under ultrasonic
      control. All the patients underwent draining operations. Determination was made
      of optimal terms of operative treatment under the ultrasonic control depending on
      the character of pathological fluid accumulation; of rational approaches to the
      abscess cavity to support the safest passing the needle through the
      retroperitoneal space tissues. An algorithm of management of the patients at the
      stages of both stationary and ambulatory treatment was developed. An analysis of
      causes of the approach conversion after minimally invasive draining operations
      was made. Draining operations under USI control in most cases of retroperitoneal
      abscesses allowed sanitation of purulent cavities without open operations.

PMID- 20804024
TI  - [Transcranial approach to the cranio-orbital area and orbital cavity].
AB  - Almost 90 years has passed from the moment of the development of transcranial
      approach to the cranio-orbital area and orbital cavity. But the application of
      the method was limited due to using mainly extracranial approaches. The authors
      have analyzed results of studying the parameters of transcranial approach to 32
      orbits of 16 corpses of adult subjects, and results of treatment of 24 patients
      with neoplasms of the cranio-orbital area and orbit, operated by transcranial
      approach. The indications to different modifications of the approach and to each
      of the intermuscular approaches to the orbital nerve were established.

PMID- 20804025
TI  - [Invasion of nerves and vessels in locally spread differentiated cancer of the
      thyroid gland: surgical strategy].
AB  - The author considers clinical manifestation, surgical strategy, immediate and
      long-term results of operative treatment of 177 (38.1%) patients with invasion of
      nerve trunks and 147 (31.6%) patients with spread of "neglected" carcinomas of
      the thyroid gland on the vessels of the neck and mediastinum. It was shown that
      most often locally-spread differentiated carcinomas and their metastases involve
      recurrent nerves (31.0%) and internal jugular veins (24.1%) in the pathological
      process. Thorough preparation of the nerves and arterial trunks using optical
      magnification allowed avoidance in most cases of circular resections of these
      structures (in 97.6% and 97.7% respectively) without a considerable elevation of
      the level of recurrence of tumors (in 3 out of 43 patients). Intraoperative
      electrophysiological monitoring was an objective factor of decision on the
      operation volume on the recurrent and accessory nerves as their resection and
      neurorrhaphy. The level of specific (5.6%) and nonspecific (6.7%) postoperative
      complications in patients with locally spread of CTG was decreased approximately
      by 50% during the last decade. Only combined operations gave perspectives for
      survival and recovery for most patients of the group under consideration.

PMID- 20804026
TI  - [Problem aspects of diagnostics and surgical treatment of Itsenko-Cushing
      syndrome].
AB  - The author has analyzed results of examination and treatment of 142 patients with
      Itsenko-Cushing syndrome. It was established that careful observation of the
      diagnostic algorithm (estimation of the blood cortisol, adrenocorticotropic
      hormone level, tests with 8 mg dexamethasone, MRI of adrenal glands and
      hypophysis with obligatory using contrast paramagnetic substances) allowed
      differentiation of basic forms of endogenous hypercorticalism: Itsenko-Cushing
      disease in 83.1%, cortisol-productive adenoma cases in 16.9%. This approach
      ensures rational strategy of treatment, good outcomes and high quality of life.

PMID- 20804027
TI  - [First experience with gel plasty of the anal canal in children with fecal
      incontinence].
AB  - Fecal incontinence in children after surgical correction of anorectal defects and
      trauma of the holding apparatus of the rectum in certain cases can be dependent
      on low basal pressure in the anal canal at the expense of incompetence of the
      interior sphincter muscle of the anus. In order to eliminate low pressure in the
      anal canal we introduced polyacrylamide gel "DAM +" into its submucous layer. The
      introduction of this volume-forming substance into the anal canal was an
      effective procedure. Fecal incontinence became less in all cases, and completely
      regressed in 50% of the patients.

PMID- 20804028
TI  - [Optimization of the technique of the vascular anastomosis formation in
      reconstructive surgery of lower extremity arteries].
AB  - In reconstructive surgery of arteries of the femoro-popliteal-tibial segment the
      leading role belongs to autovenous bypass surgery. The standard kind of vascular
      bypass applied during this procedure is bypass "autovein end to the artery side"
      using the "parachute technique". The classical method means constant help of an
      assistant, certain inconvenience associated with inadequate fixation and
      positioning the autovein end, it also does not exclude risk of traumatism of the
      bypass posterior wall. The article presents an optimized variant of the technique
      of forming the "autovein end to the artery side" bypass using improved surgical
      instruments: atraumatic pincers and retractor and a proposed for the first time
      vascular dilatator.

PMID- 20804029
TI  - [Long-term results of conservative treatment of pyo-destructive diseases of the
      lungs and parapneumonic empyema].
AB  - An analysis of results and treatment outcomes of 178 patients has been made. The
      patients were examined 1, 3, 6, 12, 24 months after discharge from hospital. The
      parameters characterizing residual cavities, pneumofibrosis, pleural fibrosis and
      changes in the bronchial tree were analyzed. Recovery was noted in 172 patients
      (96.63%). According to CT scan data positive dynamics in the reparative processes
      in the lungs and pleural cavity could be seen. No relapses of the purulent
      processes and development of lung cirrhosis were noted.

PMID- 20804030
TI  - [Use of videolaparoscopy in treatment of peritonitis of appendicular origin].
AB  - Videolaparoscopic appendectomy was carried out in 108 patients with acute
      destructive appendicitis complicated by peritonitis. Local peritonitis was noted
      in 65 patients, diffuse peritonitis in 33 patients, periappendicular abscess in
      10 patients. Postoperative complications were observed in 6 (5.6%) patients.
      Nobody died. A comparison of results of treatment with a group of 143 patients
      who underwent appendectomy by laparotomic approach has shown that after
      endovideosurgical treatment there was no such a serious complication as early
      adhesive intestinal obstruction. The number of wound complications statistically
      reliably decreased as well as the time of stay at hospital. The authors consider
      that videolaparoscopic appendectomy should be used in treatment of peritonitis of
      appendicular origin much wider.

PMID- 20804031
TI  - [Decision on the rational surgical strategy in elderly and senile patients with
      cholelithiasis].
AB  - Results of treatment of 697 elderly and senile patients with cholelithiasis and
      its complications were analyzed. It was established that decision on the rational
      surgical strategy in cholelithiasis patients of the older age group depended not
      on the patients' age, but on results of evaluation of their somatic status and
      the degree of preoperative correction, the presence and kind of complications of
      the main disease, and on the state of the bile-excreting system at different
      stages of diagnosing and treatment. The differentiated and substantiated strategy
      and the present day minimally invasive diagnostic and medical technologies
      considerably decrease risk of operative interventions, diminish the number of
      complications and thus improve the results of surgical treatment of patients of
      the older age groups having cholelithiasis.

PMID- 20804032
TI  - [Method of cholecystectomy for large Hartman pocket inosculated with biliary
      tracts].
AB  - The patients were divided into 2 groups according to the method of
      cholecystectomy. The 1st group included 36 patients operated on by a traditional
      method. The 2nd group consisted of 34 patients operated on by the proposed method
      of cholecystectomy (invention application N 2008103639) developed at the
      department of hospital surgery of the Ulianovsk state university. Complications
      were noted more often in the first group of patients: injury to the common bile
      duct (5.6%), bleeding from the gallbladder bed (11.1%), bile excretion (8.3%).
      Complications in the second group: bleeding from the gallbladder bed (2.8%). The
      proposed method of cholecystectomy for large Hartman pocket inosculated with
      biliary tracts allows a decrease of such complication as bleeding, bile
      excretion, excludes injuries of the common bile duct.

PMID- 20804033
TI  - [Chronic complicated pancreatitis. Diagnostics and surgical treatment].
AB  - The article presents an analysis of surgical treatment of 186 patients with
      complicated forms of chronic pancreatitis. Potentials of different instrumental
      techniques of investigations in diagnostics of complications of chronic
      pancreatitis are analyzed. Performance of retrograde cholangiopancreatography in
      chronic pancreatitis was shown to be expedient. Potentials of minimally invasive
      technologies and effectiveness of these interventions in different complicated
      forms of chronic pancreatitis were studied. Differentiated approach to decision
      on the kind and volume of operation depending on the complication character was
      shown. The proposed diagnostic algorithm and medical strategy allowed
      satisfactory immediate results to be obtained in this difficult group of
      patients.

PMID- 20804034
TI  - [Investigation of antioxidant properties of preparations for local treatment of
      pyo-inflammatory diseases of soft tissues].
AB  - Antioxidant properties of different medicinal agents for purulent diseases were
      studied.The indices of luminol-depending chemiluminescence of whole blood in
      donors and in patients with purulent wounds, indices of chemiluminescence of
      homogenates of the purulent wounds tissues before and after treatment were
      studied. A comparative characteristic of the influence of medicinal agents
      "Poliderm", "Voscopran", "Polisorb", "Levomekol" is given, which are used in
      local treatment of purulent wounds, on free-radical oxidation in model systems in
      vitro.

PMID- 20804035
TI  - [Phlebothrombosis of the amputation femur stump: certain aspects of pathogenesis
      and prophylactics].
AB  - An experience with treatment of 455 patients who underwent transfemoral
      amputation was analyzed. In 54 patients (11.9%) phlebothrombosis of the femur
      stump developed in the early postoperative period. Certain little studied
      problems of pathogenesis of the complication in question are considered, possible
      variants of the clinical picture are described. Negative role of thrombosis of
      the femur stump veins is shown in the development of thromboembolism of the lung
      artery that was a direct cause of death of 20 patients. Prophylactics of stump
      phlebothrombosis allows getting less frequency of the development of this
      complication, decreased lethality, improvement of quality of life and duration of
      life of patients after transfemoral amputation.

PMID- 20804036
TI  - [Comparison of the information value of traditional methods of visualization and
      MP-mammography before performing organ-saving operations for cancer of the
      breast].
AB  - The breast MRI with contrast enhancement, sonography and mammography were
      performed in 82 female patients (mean age 54 +/- 3 years) with breast malignancy.
      Mammography and USI detected correct size of tumor only in 57 out of 82 cases
      (69.5%), in 21 cases (25.6%) the size of the tumor were underestimated, in 4
      cases (4.9%) overestimated. MRI showed precise size of tumors in 91% of cases
      with underestimation in 5% and overestimation in 4% of cases. Breast MRI gives
      more accurate estimation of the tumor extent compared with US and mammography
      (91.4% versus 69.5%). Both MRI and conventional diagnostic tools showed precise
      size of the tumor in 68% of the patients. Thus, MRI gives more accurate
      estimation of the tumor extent than US and mammography, which is of particular
      importance in the preoperative evaluation when breast-conserving surgery is
      planned with the main purpose to reach the optimal balance between radical
      treatment and cosmetic effect.

PMID- 20804037
TI  - [A successful extracorporal liquidation of the renal artery aneurysm with
      reconstruction of the artery and autotransplantation of the kidney in treatment
      of renovascular hypertension].

PMID- 20804038
TI  - [Principles of diagnostics and treatment in bezoar of the stomach].

PMID- 20804039
TI  - [Enlargement of the volume of surgical procedures in perforative ulcer of the
      duodenum].

PMID- 20804040
TI  - [Symposium of the European Society of Endocrine Surgeons (March 19-21, 2009)
      "Current technology in surgical treatment of patients with primary
      hyperparathyroidism: argument of prospects"].

PMID- 20804041
TI  - [Iatrogenic aneurysms of blood vessels].

PMID- 20804042
TI  - [Does the etiology of acute respiratory distress-syndrome influence the strategy
      of respiratory therapy?].

PMID- 20804043
TI  - [Pyoderma gangrenosum as a surgical problem].

PMID- 20804044
TI  - [Syndrome of "postoperative fatigue"].

PMID- 20804045
TI  - [Role of endogenous iron in tumor sensitization to antitumor therapy].

PMID- 20804046
TI  - [Green tea, a promising source of novel antitumor drugs?].

PMID- 20804048
TI  - [Virally mediated immunotherapy as a component of combined treatment in malignant
      cerebral glioma].

PMID- 20804047
TI  - [Predictors and prognostic models in childhood and adolescent Hodgkin's disease].

PMID- 20804049
TI  - [Age-related features of observed and relative survival among ovarian cancer
      patients in St. Petersburg, Russia].

PMID- 20804050
TI  - [Markers of malignant growth as a component of morphologic pattern in human
      biological fluids].

PMID- 20804051
TI  - [Reconstruction of the chest using titanium devices after extensive resection of
      ribs and breast bone in cancer patients].
AB  - We evaluated the potential of surgical treatment of patients with extensive tumor
      related lesions of the chest. Combined resection of tumor together with different
      parts of the chest and plastic surgery aborted further development of grave
      complication and paved the way for subsequent antitumor therapy. Access to
      surgical treatment can be extended to more advanced cancer sufferers through
      plastic surgery, thus contributing to better quality of life and longer survival.

PMID- 20804052
TI  - [Use of high-energy intraluminal brachytherapy in radio- and radiochemotherapy
      for anal cancer].
AB  - Complete local response to radio- and chemoradiation for anal cancer was improved
      due to use of high-energy dosage of intraluminal brachytherapy (complete clinical
      regression (chemoradiation)--85.7%; combined irradiaton--75%). No signs of tumor
      progression have been reported in 20 survivors (median duration--21.6 months)
      (mean recurrence-free survival--12.5 months). Loco-regional relapse was in 4,
      local--2 patients. Intrapelvic lymph nodes were involved in 2 cases of previously
      morphologically confirmed regression of primary tumor. 18-month-long recurrence
      free survival was in 86.3%, colostomy-free--91.6%. When combined with distant
      irradiation (+/-chemotherapy), brachytherapy is a relatively effective, safe and
      well tolerated procedure.

PMID- 20804053
TI  - [Effect of previous diabetes therapy on tumor receptor phenotype in breast
      cancer: comparison of metformin and sulphonylurea derivatives].
AB  - According to some existing data, unlike sulphonylurea (SU) and insulin
      derivatives, treatment with biguanide metformin, for reasons still unknown, may
      diminish breast cancer (BC) morbidity in diabetic females. For its part, diabetes
      is known to worsen survival of BC patients although there is no evidence of a
      pathway by which antidiabetic therapy might influence the key prognostic feature
      of BC tissue--the tumor receptor phenotype. Combination of BC and diabetes (n=90)
      was studied. SU drugs were received for at least 12 months by 22 patients,
      biguanide metformin alone or in conjunction with SU by 15, insulin by 5, and
      dietary treatment alone--by 48 pts. Percentage of estrogen receptor-positive
      tumors did not vary significantly from group to group. However, progesterone
      receptor-positive (PR+) tumors in metformin-treated patients were revealed more
      often than in those receiving SU alone (p = 0.43) or with insulin (p = 0.041),
      respectively. Hence, previous treatment with metformin is expected lead to higher
      incidence of PR+ tumors which in turn may stimulate efficiency of hormonal
      therapy only in relevant group of diabetic BC patients.

PMID- 20804054
TI  - [Low-molecular DNA in blood plasma and spinal fluid of cancer patients].
AB  - Enhanced preoperative levels of low-molecular DNA in blood plasma and in
      cerebrospinal fluid were established in cancer patients. They rose even higher
      after surgery due to stress. Possible mechanisms are discussed.

PMID- 20804055
TI  - [Features of carcinogenesis and aging in knockout male mice PARP-1].
AB  - Poly(ADP-ribosyl)ation polymerase-1 (PARP-1) is a major factor of DNA repair. Age
      related parameters such as body weight and blood cholesterol in knockout male
      mice PARP-1 were more pronounced as compared with controls. Mean life span was
      shorter (486 +/- 31.7 and 723 +/- 22.6 days, respectively, (p = 0.000005) while
      initial risk of death (beta) was 8 times as high as in mice PARP-1(+/+). Mean
      latency of all tumors in knockout and control mice was 656 +/- 43.5 and 782 +/-
      33.8 days, respectively, (p < 0.05). Among the most frequent neoplasms were
      tumors of the liver (experimental--22% and control--8%, respectively) (p = 0.03)
      and lungs (8% and 12%, respectively). Hence, mice PARP-1(-/-) revealed certain
      typical charhacteristics of accelerated aging, shorter life span, earlier
      carcinogenesis and higher rates of liver tumor incidence as compared with mice
      PARP-1(+/+). Our evidence highlights the role of DNA repair in carcinogenesis and
      aging.

PMID- 20804056
TI  - [Tumor-specific expression of PBOV1, a new gene in evolution].
AB  - We identified mRNA of the newly discovered gene PBOV1 in a multitude of samples
      from tumors of the brain, lung, liver, gallbladder, colon, small intestine,
      mammary gland, uterus, ovary, ureter, adrenals, parotid, thymus and spleen.
      However, out of 29 intact adult and 8 fetal tissues, only pancreas was
      characterized by weak expression of the gene. Our results demonstrated that the
      PBOV1 gene expression is tumor-specific and has a potential as tumor marker. It
      is worth mentioning that we had predicted that property on the basis of available
      evolutionary data.

PMID- 20804057
TI  - [Analysis of prognostic factors influencing metastatic potential in breast
      cancer].
AB  - The paper discusses our data on evaluation of prognostic factors influencing
      metastatic potential of breast cancer and correlations which determine likelihood
      of tumor spreading to the lungs. Only the most plausible correlation coefficients
      (Chandelle) (p < or = 0.001) were used (0.3 relative to absolute module). The
      correlations between the totals of points (RR) and probability were: 115-199--71
      100%; 55-114--31-70%, and 20-54--less than 30%.

PMID- 20804058
TI  - [Use of hypotensive anesthesia in endotracheo-bronchial surgery for tumor-related
      lesion of the trachea and/or central bronchi].
AB  - The paper presents a review of the literature data and our own experience with 25
      endotracheabronchial operations for tumor-related stenosis of the central bronchi
      and/or trachea using hypotensive anesthesia. The latter condition was induced by
      speeding up propofol injection and maintaining general anesthesia at 4.4-9 mg/kg
      x hr. Mean arterial pressure was lower than in control (60-65 vs. 70-80 mmHg,
      respectively). As a result, blood loss fell 138-100 +/- 11 ml whereas gas
      exchange indices improved (pO2 112-87 mmHg). At intubation stage, rise in mean
      arterial pressure and heart rate was avoided.

PMID- 20804059
TI  - [Toxic effect of radiotherapy on metastatic lesions of the lung].
AB  - The study was concerned with identifying toxic effect of certain methods of
      radiotherapy of metastatic lesions of the lung. Leukocyte index intoxication
      (Kalf-Kalif), paramecin test and mean molecule level determination were used. The
      worst endogenous intoxication was found to be caused by irradiating four
      consecutive fields of the mediastinum. The least damage was caused in combination
      with artificial pneumothorax. Use of smaller-size fields of irradiation was
      followed by a significant drop in adverse side-effects.

PMID- 20804060
TI  - [Intravenous photodynamic therapy: first experimental and clinical data].
AB  - We carried out the first investigation to establish rat tumor M-1 by laser
      irradiation of the large blood vessel zone in the inguinal triangle in
      conjunction with photosensitinogen growth inhibition. Relatively small-size
      metastases to the lymph nodes and liver (stage III-IV) were identified after the
      blood was exposed to laser radiation in combination with intravenous injection of
      photosensitinogen under clinical conditions.

PMID- 20804061
TI  - [Leiomyosarcoma of the spleen].

PMID- 20804062
TI  - [Radiation-related esophagitis].

PMID- 20804063
TI  - [Current approaches to treatment of invasive sqaumous-cell carcinoma of the
      penis].

PMID- 20804064
TI  - [Meta-analysis of the effect of experience and specialization on the long-term
      results of surgery for colorectal cancer].

PMID- 20804065
TI  - [Dedication to the ideals of science--on the occasion of the 110th birth
      anniversary of academician R.E. Kavetskii].

PMID- 20804066
TI  - [Using laboratory primates in medical experiment].

PMID- 20804067
TI  - [Anti-inflammatory role of cholinergic and serotonergic systems in shock].
AB  - Development of anaphylactic shock initiated with the horse serum (anaphylactic
      index = 4.0 +/- 0.0 arbitrary units) leads to acute decrease in spleen
      concentration of serotonin (in shock--0.443 +/- 0.005; basal level--1.532 +/-
      0.004 ng per mg of protein). Unlike of anaphylaxis, development of endotoxic
      shock in rats, caused by introduction of a sublethal dose (20 mg/kg) of
      lipopolysaccharide, results in acute increase in serotonin concentration (at a
      shock--56.588 +/- 0.006, basal level--5.465 +/- 0.005 ng per mg of protein) and
      marked tachycardia (+76 +/- 8, intact rats--+2 +/- 1 beats per min).
      Administration of atropine with galantamine leads to the most essential decrease
      of anaphylactic reaction (1.5 +/- 0.3 arbitrary units). Administration of choline
      alfoscerate (-16 +/- 3 beats per min) or galantamine (+9 +/- 2 beats per min)
      significantly reduces tachycardia. Data show, that inhibition of the central
      cholinergic mechanisms leads to increase and their excitation--to decrease in
      activity of the spleen serotonergic system. So, spleen concentration of serotonin
      is connected with a target of shock defeat (lungs or heart).

PMID- 20804068
TI  - [Autoantibodies to glutamate, GABA, dopamine and serotonin in the dynamics of
      development of chronic brain epileptization in mice C578l/6].
AB  - In experiments on mice C57Bl/6 was studied the possibility of production of
      glutamate, GABA, dopamine and serotonin autoantibodies in the dynamics of
      development of chronic brain epileptization--pharmacological kindling, induced by
      daily administration of pentylenetetrazol in subconvulsive dose (30 mg/kg) during
      24 days. 14 days after the start of the kindling autoantibodies to glutamate was
      detected in all experimental animals, to CABA--in 60% of mice, to serotonine--in
      70%, and to dopamine--in 90%. After 24 days--the number of animals with
      autoantibodies to glutamate and dopamine was decreased, to serotonin--increased,
      and to GABA--was not altered. It was shown the relationship between detection
      neurotransmitters autoantibodies and severity of the convulsive reaction.

PMID- 20804069
TI  - [The influence of acute alcohol intoxication on glycogen content in the liver and
      sceletal muscles].
AB  - The influence of ethanol on glycogen value in liver and skeletal muscle was
      investigated at rats and forensic cases. In 24 hours after ethanol intake
      glycogen value in rat's liver was low. By autopsy examinations liver glycogen
      value was low in cases as acute ethanol poisoning as coronary heard diseases with
      alcohol condition. No differences in muscle glycogen level were revealed. The
      results may be used in postmortem interval at differential diagnosis when blood
      alcohol is absence or traces.

PMID- 20804071
TI  - [Modulation of platelet tyrosine phosphatases by arachidonic acid metabolites in
      diabetes mellitus complicated with acute pyogenic inflammation].
AB  - To estimate the ability of intracellular tyrosine phosphatases modulation by
      arachidonic acid metabolites in patients with diabetes mellitus 2 type during
      foot wounds healing the inhibitory analysis of platelets aggregation induced by
      ATP plus inhibitors of tyrosine phosphatases, cyclooxygenases and 5-lipoxygenases
      was performed in 16 patients during hospitalization, at 3-5, 10-14 and 30 days of
      therapy. It was shown that foot wound healing in diabetic patients was associated
      with optimization of proteins tyrosine phosphorylation and cells arachidonic acid
      metabolism. It means the diagnostic significance of tyrosine phosphorylation and
      eicosanoids to interpret the result of wound healing at diabetes mellitus.

PMID- 20804070
TI  - [Perinatal outcomes in pregnant women with diabetes mellitus and different level
      of autoantibodies to insulin and its receptors].
AB  - The levels of idiotypic (AB1) and antiidiotypic (AB2) antibodies were
      investigated in pregnants (n = 248) suffer from diabetes. It was proved that AB2
      to insulin conditionally can be regards as antibodies to insulin receptor. It was
      shown that condition of newborns much depends on levels of these antibodies and
      their proportion. Condition of newborns from women with isolated high levels of
      AB1 to insulin was much better in comparison with ones from mothers with isolated
      high levels of AB2 to insulin. Conception about mechanisms of acting of AB1 and
      AB2 to insulin on fetus was represented.

PMID- 20804072
TI  - [Myelokaryocytes and leukocytes of circulating blood in elimination of
      erythrocyte transporting immune complexes and xenogenic antigens].
AB  - Interacting with erythrocytes which transport immune complexes and xenogenic
      antigens myelocariocytes and leukocytes of circulating blood produce from them
      erythroclasic clusters in bone marrow and autorosettes in circulating blood.
      Formation of these cellular associations is completed with exocytic lysis of
      included in them erythrocytes by myelocariocytes and leukocytes. It is supposed
      that the lysis of erythrocytes within erythroclasic clusters and autorosettes is
      the final stage of erythrocytic clearance of immune complexes and xenogenic
      antigens.

PMID- 20804073
TI  - [Characteristics of motility function of the esophagus in patients with aphagia].
AB  - In article is shown the results of investigation of motility function of
      esophagus in 18 patients with pharyngoesophageal obstruction. 16 patients were
      operated. The essence of method was in simultaneous registration of UES
      intracavitary pressure and impedance. We discovered that all patients have both
      not opening of for the swallow and disturbances of sphincteral function of LES
      and contractive activity of thoracic esophagus. Dynamic of this parameters in 7
      operated patients was monitored. Obtained data were analyzed according to
      clinical results of surgery.

PMID- 20804074
TI  - [Hemostasis changes and their correction by adaptogen].
AB  - The paper presents an investigation into the changes in the hemostasis system of
      rats during extreme exercises. It has been observed that a single two-hour
      swimming exercise and an eight-hour imposed running in the treadbahn are
      accompanied by the expressed shifts in hypercoagulation with the signs of
      thrombinemia. On the background of the decrease in the anticoagulative and
      fibrinolytic activity it creates a serious threat of intravascular blood
      coagulation. The preliminary thirty-day course of extractum Eleutherococci
      eliminated the signs of intravascular blood coagulation.

PMID- 20804075
TI  - What is your greatest marketing challenge?

PMID- 20804076
TI  - The forecast for health care.

PMID- 20804077
TI  - Thrive.

PMID- 20804078
TI  - The joys of going blue.

PMID- 20804079
TI  - Star power.

PMID- 20804080
TI  - Ambassadors of innovation.

PMID- 20804081
TI  - Detox your workplace.

PMID- 20804082
TI  - Yours for a song.

PMID- 20804083
TI  - A legal primer for social media.

PMID- 20804084
TI  - Leading with two ears and one mouth.

PMID- 20804086
TI  - [Breastfeeding and allergies].
AB  - Early breastfeeding has been suspected to influence the development of allergies
      of the child. Original studies analyzing this influence are promiscuous regarding
      both the determination of the causative agent, i.e., quality of lactation, and
      the evaluation of the final result. Identifying allergic symptoms is sundry and
      often based on information provided by the parents. The studies discussed in this
      review take into account genetic predisposition, the most important underlying
      factor of allergy, but based on these results, early breastfeeding does not have
      a significant influence on the development of allergies irrespective of genetic
      predisposition.

PMID- 20804085
TI  - [The treatment of adult glioma is multiphasic].
AB  - The prognosis of glioma has improved. Even patients with glioblastoma surviving
      over two years is not rare. The quality of life has improved because of earlier
      diagnosis and more precise surgical and radiotherapy techniques. In grade 3-4
      gliomas treatment modalities are combined. In grade 2 there are several options
      for postoperative treatment. Recurrencies are treated actively irrespective of
      the initial histological grade of the tumor. Chemotherapy is used both combined
      with radiotherapy and as a single treatment at recurrence. The best results are
      achieved with close co-operation among different specialities in neuro-oncology,
      most effectively in weekly meetings. Fluent flow of information between health
      care units promotes the best quality of life for glioma patients.

PMID- 20804087
TI  - [Genetic testing in cardiologic diagnostics].
AB  - Gene tests may be beneficial in cases of suspected hereditary heart disease or
      hyperlipidemia. A gene defect can be found in approx. 20% of those with
      hypertrophic cardiomyopathy in Finland. In the long QT syndrome, four major
      mutations account for almost three fourths of the Finnish cases. The gene defect
      causing familial hypercholesterolemia is found in approx. 90% of cases. If the
      familial gene defect is revealed, DNA testing can be applied to find the
      symptomless carriers of the mutation who require follow-up, and to liberate those
      not carrying the mutation from the follow-up.

PMID- 20804088
TI  - [Treatment of pseudomyxoma peritonei is developing].
AB  - In pseudomyxoma peritonei a mucinous tumor of the appendix spreads into the
      abdominal cavity. Cytologic picture of the tumor may be benign, malignant or
      intermediary. The symptoms were previously relieved by repeated resections of the
      tumor mass, whereby even the most benign form of the disease progressed slowly. A
      method has now emerged in which radical-aimed surgery is combined with
      intraperitoneal lavage with a warmed solution of a cytotoxic agent. This
      treatment is associated with a morbidity of 33 to 56% and a mortality of 0 to
      18%. Controlled studies have not been carried out on the novel treatment.

PMID- 20804089
TI  - [Are immunological treatments beneficial for malignant melanoma of the skin?].
AB  - Treatment results of metastatic malignant melanoma of the skin have failed to
      exhibit significant improvement for 30 years. Owing to the poor efficiency of
      cytotoxic therapies, attention has focused on the patient's own immune system and
      its strengthening or "teaching" to counteract the melanoma tissue. The most
      significant forms of immunotherapy currently include the interferons, interleukin
      2 and antibody therapy directed against a specific T-lymphocyte associated
      antigen (CTLA-4). So far, therapeutic vaccines for melanoma have not ended up
      into routine clinical use.

PMID- 20804091
TI  - [Generic competences in medical undergraduate education].
AB  - BACKGROUND: In medical practice physicians need both vocational and generic
      competences. The importance of generic competences In medical undergraduate
      curriculum is often poorly appreciated. MATERIAL AND METHODS: We assessed by
      questionnaires the opinions of medical students of the importance of generic
      competences in medical practice and of their anticipated development during
      undergraduate medical education in the University of Turku. RESULTS: Students
      thought that application of medical knowledge in practice, information
      acquisition, independent working and problem solving skills are important in
      medical practice and are also well-handled in undergraduate education. On the
      other hand, students felt that competences, like coping at work, tolerance of
      uncertainty and organizing skills are often needed in medical profession, but are
      insufficiently considered in basic education. CONCLUSIONS: The balance between
      importance in medical practice and educational development of generic competences
      should be more explicitly considered in undergraduate medical teaching.

PMID- 20804090
TI  - [Shwachman-Diamond syndrome--a diagnostic challenge].
AB  - Shwachman-Diamond syndrome is a rare autosomal recessive disorder caused by
      mutations in the SBDS gene. The cardinal symptoms arise from exocrine pancreatic
      insufficiency and bone marrow dysfunction. These lead to malabsorption and
      haematological abnormalities, susceptibility to infections and to increased risk
      of leukaemia. Skeletal involvement presents as growth failure, metaphyseal
      dysplasia and osteoporosis. The majority of patients also have liver dysfunction,
      learning difficulties and oral and dental problems. Although the disease
      typically presents in early childhood, phenotypic features change over time and
      the diagnosis becomes more challenging.

PMID- 20804092
TI  - [Current care guidelines: Specific language impairment (SLI)].
AB  - Specific language impairment (SLI) affects a child's functional, social and
      communication capacity. The associated language comprehension problems may be
      difficult to recognise in everyday life. Although the diagnosis of SLI is most
      reliable after four years of age, early support must be provided as soon as there
      is any suspicion of SLI. Diagnosis, rehabilitation and other therapeutic
      manoeuvres are based on multiprofessional co-operation. Key factors in achieving
      a favourable prognosis are (1) adequate and early support for language learning
      and daily participation, (2) adequate and timely rehabilitation and (3) paying
      attention to problems associated with SLI in school.

PMID- 20804093
TI  - [Update on current care guidelines; childhood headache].
AB  - Childhood headache is a common condition. For childhood migraine, paracetamol and
      ibuprofen are the recommended medications. Less evidence is available on the
      effectiveness of triptans in children and adolescents than in adults, but
      consideration can be given to nasal sumatriptan and possibly oral rizatriptan,
      nasal and oral zolmitriptan. Propranolol is the first-line prophylactic
      medication for migraine. Less evidence exists on the effectiveness of
      pharmacotherapy for cases of tension headache than for migraine. The majority of
      children who suffer from recurrent headaches can be effectively treated in the
      primary health care.

PMID- 20804094
TI  - [New routes for formation of guardians of the course].

PMID- 20804095
TI  - [Alport's syndrome and benign familial haematuria: light and electron microscopic
      studies of the kidney].
AB  - INTRODUCTION: Hereditary nephropathy is clinically characterized by the familial
      occurrence in successive generations of progressive haematuric nephritis and
      neural hearing loss. Hereditary nephropathy of Alport's syndrome (AS) and benign
      familial (recurrent) haematuria (BFH) are morphologically characterized by
      specific and diagnostically important thickening and splitting of lamina densa of
      the glomerular basement membranes. Those lesions can be recognized only by
      electron microscopy. Hereditary nephritis is usually present clinically with
      haematuria, and new mutations without a family history of haematuria. It is
      therefore important to differentiate hereditary nephritis from BFH and no
      familial haematuria. Thus, electron microscopy is essential in diagnosis of
      haematuria. OBJECTIVE: The aim of this study was to describe, by light
      microscopy, constellation of renal alterations by which hereditary nephropathy
      can be recognized with high probability as well as to compare the diagnostic
      validity of the findings observed by light and electron microscopy in AS and BFH.
      METHOD: We examined 48 renal biopsies of the patients with hereditary
      nephoropathies by light and electron microscopy. Tissue samples were fixed in
      buffered paraformaldehyde and embedded in paraffin for long-term preservation.
      For the electron microscopy analysis, the following fixation in 4% glutaraldehyde
      tissue was postfixed in 1% osmium tetroxide. Thereafter, the following
      dehydration procedure tissue slices were embedded in epon. RESULTS: Our results
      demonstrated that the interstitial foam cells, foetal-like glomeruli, minimal
      glomerular abnormalities with stain less intense in basement membranes, mild
      irregular mesangial widening, focal thickening of Bowman's capsule, foci of
      dilatation tubules, tubular ectasia and atrophy, erythrocyte tubules casts were
      present in hereditary nephritis. Additionally, light microscopic biopsy findings
      in patients with BFH were either normal or revealed minor changes (e.g. increased
      mesangial matrix). All biopsies were reevaluated by electron microscopy and
      ultrastructural findings confirmed the diagnosis of hereditary nephropathies.
      CONCLUSION: The findings observed by light microscopy represent an important step
      that leads to a definitive diagnosis of AS and BFH.The definitive diagnosis,
      however, depends on electron microscopy.

PMID- 20804096
TI  - [The significance of Goodpasture antigen in hereditary nephritis].
AB  - INTRODUCTION: Two types of hereditary nephritis, nonprogressive and progressive,
      clinically present as asymptomatic haematuria, sometimes combined with
      proteinuria. At the onset, in both types, light microscopic changes are minimal,
      immunofluorescence findings are negative, and diagnosis can be made only upon
      electron microscopic findings that are considered to be specific. OBJECTIVE: The
      aim of this study was to determine the significance of Goodpasture antigen
      detection in diagnosis of progressive and nonprogressive hereditary nephritis in
      its early phase. METHOD: Analysis of renal biopsy specimens was done in patients
      with hereditary nephritis that were followed from 1990 to 2005. Progression of
      renal disease was examined in 14 patients with Alport's syndrome, 10 patients
      with thin basement membrane disease, and 6 patients with unclassified hereditary
      nephritis diagnosed. For all these cases, indirect immunofluorescence study with
      serum from a patient with high titer of Goodpasture autoantibodies that recognize
      the antigenic determinants in human glomerular and tubular basement membrane was
      performed. RESULTS: In 11 out of 14 cases diagnosed as Alport's syndrome, there
      was negative staining with Goodpasture serum, and in 3 additional cases with
      Alport's syndrome, expression of Goodpasture antigen in glomerular basement
      membrane and thin basement membrane was highly reduced. In all 10 patients with
      thin basement membrane disease, immunofluorescence showed intensive, bright
      linear staining with Goodpasture serum along glomerular and tubular basement
      membrane. In 2 out of 6 patients with unclassified hereditary nephritis,
      Goodpasture antigen expression was very strong, in one patient it was very
      reduced, and in 3 patients it was negative. CONCLUSION: The results of our study
      show that Goodpasture antigen detection plays a very important role in
      differential diagnosis of progressive and nonpregressive hereditary nephritis,
      particularly in early phases of the disease.

PMID- 20804097
TI  - [Renal replacement therapy in adult dominant polycystic kidney disease-
      multicentre study].
AB  - INTRODUCTION: Adult polycystic kidney disease (APKD) is the most common
      hereditary kidney disease in humans. The course of the disease is accompanied by
      numerous complications. OBJECTIVE The aim was to assess the prevalence, clinical
      course and outcome of adult dominant polycystic kidney disease (ADPKD) patients
      on renal replacement therapy. METHOD: Medical data on 700 haemodialyzed (HD) and
      500 transplanted patients treated in 10 Serbian centres from 1996 to 2000 were
      retrospectively analyzed. While ADPKD patients accounted for 13% of HD patients
      in Serbia in 2000, in the period between 1996 and 2000, the percent of patients
      with ADPKD in the population of patients starting HD in 8 examined centres
      changed from 13.5% to 6.9%. RESULTS: The total number of 180 ADPKD patients on HD
      was analyzed (96 males; aged 55 years at HD onset). Their HD lasted between 1 and
      22 years: males started HD 1.3 years earlier and spent on HD 1.1 years less than
      females. In 53% of HD patients one or more family members had ADPKD but the cause
      of death was unknown for many family members. Hypertension was present in 75% of
      ADPKD patients, anaemia in 37% and other organ involvement (usually liver) was
      found in 53 patients. Fifty patients experienced AV fistula thrombosis and a
      vascular prosthesis had to be used in 9 of them. A hundred and two HD patients
      died (aged between 38 and 78 years, on HD for 5.3 years). The causes of death
      were stroke (19.6%), cardiovascular diseases (29%), infections, while 5% of
      patients died with the picture of acute abdomen. Among 500 transplanted patients,
      there were 20 patients with ADPKD (11 males, ages between 35 and 56 years at the
      time of transplantation) and 14 of them received graft from cadaver donor. Uni-
      or bilateral nephrectomy was done in 4 patients in the pretransplant preparation,
      and in another two early after transplantation due to urinary infection. Three
      patients restarted HD in the first 3 months after transplantation due to acute
      tubular necrosis and 10 patients died 56.5 months after the transplantation. The
      known causes of death were cardiovascular disease (3 patients), severe
      gastrointestinal bleeding (2 patients), infection (2 patients) and cancer (2
      patients). CONCLUSION: The obtained results showed that it was possible to
      provide a favourable outcome of patients with APBB on renal replacement therapy
      in spite of numerous complications.

PMID- 20804098
TI  - [Polycystic kidney disease--autopsy review from the period 1987-2007].
AB  - INTRODUCTION: Polycystic kidney disease is an inherited kidney disease that
      affects both kidneys and it is characterized by diffuse replacement of renal
      parenchyma by thousands of microcysts. In time, renal insufficiency develops.
      There are two forms of PKD: ADPKD, which is detected in adults (children are
      rarely affected), and ARPK, which is detected in neonates (later presentations do
      occur, but rarely). OBJECTIVE: The aim of this study was to analyse frequency of
      polycystic kidney disease, clinical data and morphological characteristics.
      METHOD: At the Institute of Pathology, School of Medicine, Belgrade, there were
      detected 33 cases of ADPKD and 20 cases of ARPKD between 1987 and 2007. RESULTS:
      There were no differences between incidence of ADPKD in males and females.
      Average age of patients with ADPKD was 52 years. In 20 (66.7%) cases of ADPKD
      there were neither extrarenal cysts nor extrarenal manifestations detected. In
      other 13 cases, we detected extrarenal cysts: hepatic cysts in 8 cases,
      pancreatic cysts in 5 cases. In two cases, hepatic cysts were associated with
      intracranial (arachnoid cysts) and extracranial aneurysms. The most frequent
      cause of death in patients with ADPKD was end-stage disease. ARPKD affects more
      often male children compared to female. 70% of children with ARPKD were male. The
      mean age of patients with ARPKD was 1 month. 5 patients (40%) had hepatic
      fibrosis. The most frequent cause of death was respiratory insufficiency (75%).
      In 25% of patients, the cause of death was sepsis and renal insufficiency.
      CONCLUSION: Morphological and clinical manifestations of the analysed cases of
      both types of PKD are fairly consistent with literature data. Better knowing of
      aethiopathogenesis of PKD will facilitate early diagnosis, based on clinical and
      morphological characteristics and better management of the disease.

PMID- 20804099
TI  - [Immunohistochemical expression of p53 oncoprotein in Wilms tumour in relation to
      histological components, histological types and preoperative chemotherapy].
AB  - INTRODUCTION: There have been only few studies of immunoexpression of p53 in
      Wilms tumour (WT), and their results are somewhat contradictory. OBJECTIVE: The
      aim of the study was to determine p53 immunohistochemical expression in WT in
      relation to its histological components, histological prognostic types classified
      according to the SIOP Working Classification of Renal Tumours of Childhood
      (2001), and influence of preoperative chemotherapy. METHOD: The analyses are
      based on 79 primary WTs treated in single institution according to SIOP protocols
      between 1983-2001. For the immunohistochemical detection of p53, the monoclonal
      p53 antibody (DO-7, DAKO) was used. Semiquantitative grading of nuclear staining
      was done. RESULTS: The immunoexpression of p53 was significantly higher in the
      blastemal and epithelial than in the stromal component (p < 0.001). It was
      significantly correlated to WT histological prognostic types (p = 0.039).The
      exensivity of p53 immunoexpression was higher in anaplastic components but a
      difference between WT type of diffuse anaplasia and all other types was
      nonsignificant (p = 0.10). Five blastemal type WTs were p53 immunopositive and
      four immunonegative. There was no difference in p53 immunopositivity between WT
      treated with the preoperative chemotherapy and primary resected WT (p = 0.88).
      CONCLUSION: The immunoexpression of p53 in WT was significantly higher in the
      blastemal and epithelial than in the stromal component. It was in significant
      correlation with histological types of WT. The anaplastic component had
      noticeable but statistically not significantly higher p53 immunoexpression than
      non-anaplastic. The preoperative chemotherapy did not modify p53 immunoexpression
      of WT which had been found in other similar studies.

PMID- 20804100
TI  - [Congenital nephrotic syndrome].
AB  - INTRODUCTION: Congenital nephrotic syndrome is usually presented with heavy
      proteinuria, hypoproteinaemia, oedema and hyperlipidaemia in a child from its
      birth until the age of 3 months. Aetiology of the disease is mutation in the
      relevant gene or it develops secondary to various infections. The most common
      form of congenital nephrotic syndrome is caused by mutation in gene for nephrin,
      the most important protein of the slit diaphragm. CASE OUTLINE: We present the
      patient with the clinical and laboratory signs of nephrotic syndrome expressed in
      the first day of life. Despite the adequate and regular substitution,
      antiproteinuric and antithrombotic therapy, complications occurred and the
      patient deceased. Genetic analysis revealed homozygous mutation in gene for
      nephrin (614del8ins2TT). Three years later, in the patient's mother who was in
      the 12th week of pregnancy at that time, biopsy of chorionic villi was performed
      and the foetal genetic material showed heterozygosity for the same recessive
      mutation which meant that the foetus had the status of a carrier. To the best of
      our knowledge, this is the first family in Serbia in which prenatal molecular-
      genetic testing for the congenital nephrotic syndrome was accomplished.
      CONCLUSION: We wish to stress the importance of molecular diagnosis in patients
      with congenital nephrotic syndrome in order to perform early prenatal diagnosis
      in future pregnancies.

PMID- 20804101
TI  - [Dent's disease].
AB  - INTRODUCTION: Dent disease is X-linked recessive proximal tubulopathy, due to
      mutations in the CLCN5 gene. It is characterized by low molecular weight
      proteinuria, hypercalciuria, nephrocalcinosis and progressive renal failure. CASE
      OUTLINE: A seven-year-old boy was referred after endocrinological examination
      where abdominal ultrasound showed nephrocalcinosis. There were anamnestic data
      neither of oedema, macrohaematuria, nor polyuria or hypertension. There were also
      no data of chronic renal failure in the family. We determined: proteinuria (1.8
      g/day), elevated urinary excretion of Beta 2 microglobulin, microscopic
      haematuria, hypercalciuria (8-10 mg/kg/day), nephrocalcinosis, decreased tubular
      reabsorption phosphate (65%). Values of growth hormone, parathormone on thyroid
      hormone were normal. Except hypercalciuria, which was registered in the patient's
      mother, all other analyses performed in family members were between reference
      values. Diagnosis was finalized by mutation analysis, which showed S244L
      substitution on CNCL5. Mutation carrier was mother with normal phenotype.
      CONCLUSION: Dent disease is rare X-linked nephrocalcinosis. Definitive diagnosis
      of this proximal tubulopathy which leads to progressive renal damage is not
      possible without evidence of gene mutation in renal chlorine channel.

PMID- 20804102
TI  - [Development and ultrastructure of glomerular capillaries in human foetus].
AB  - Glomerulus is an important filtrating apparatus in the body. Three types of cells
      -endothelial, mesangial and visceral epithelial cells can be identified in the
      capillary tuft. Glomeruli develop during nephrogenesis which starts in the 8th
      week and ends between the 32nd and 36th week of gestation. The nephron develops
      through stages described as the vesicle, the comma-shaped, S-shaped with the
      developing glomerulus and the mature glomerulus. Glomerular differentiation
      involves the expansion of the original capillary component into the plexus that
      consists of 6-8 loops and the migration of podocytes that are arranged around
      these glomerular capillaries. Glomerular capillary differentiation represents a
      set of developmental changes of the glomerular endothelial and epithelial cells.
      The active differentiation of glomerular capillaries starts in the hemisphere of
      an inferior arm of S-shaped bodies. Endothelial precursors unite into
      precapillaries devoid of lumen. Further differentiation includes the flattening
      of endothelial cells on the basement membrane, the loss of superfluous cells, the
      development of lumen and the formation of fenestrae. The glomerular basement
      membrane is differentiated by the fusion of epithelial and endothelial basement
      membrane. The differentiation of visceral epithelial cells includes the
      development of cytoplasmic processes and the flattening of cell bodies. Primary
      cytoplasmic processes are formed from the podocyte bodies and develop secondary
      and tertiary processes or foot processes. Foot processes from one podocyte
      interdigitate with foot processes from other podocytes. In the developing
      glomeruli, there is a difference in the level of differentiation of visceral
      epithelial cells. Cells with differentiated foot processes and cells with no
      cytoplasmic processes are observed within the same glomerulus.

PMID- 20804103
TI  - Spectrum of collagen type IV nephropathies: from thin basement membrane
      nephropathy to Alport syndrome.
AB  - Alport syndrome and thin basement membrane nephropathy are common causes of
      persistent familial haematuria. They are associated with various mutations in
      type IV collagen genes. Mutations in genes, coding for alpha5 chain of collagen
      IV, cause X-linked Alport syndrome, whereas mutations in genes for alpha3 and
      alpha4 chains can cause the autosomal recessive and autosomal dominant type of
      Alport syndrome or benign familial haematuria with thin basement membrane
      nephropathy. In view of the wide spectrum of phenotypes, an exact diagnosis is
      sometimes difficult to achieve. Few studies of genotype-phenotype correlations in
      Alport syndrome have shown that various types of mutations may be a significant
      predictor of the severity of disease. Histopathologic findings in Alport syndrome
      vary from normal kidney to nonspecific focal segmental and global glomerular
      sclerosis with characteristic ultrastructural finding of thickening and splitting
      of the glomerular basement membrane. Thin basement membrane nephropathy is
      characterized by diffuse thinning of the glomerular basement membrane on an
      ultrastructural level, while by light microscopy glomeruli are mostly
      unremarkable. Because of present limitations of mutation screening techniques,
      kidney biopsy with mandatory ultrastructural analysis and immunohistochemistry
      examination for type IV collagen alpha chains remains a standard approach for
      establishing diagnosis and determining the mode of transmission of the disease.

PMID- 20804104
TI  - [Inherited podocytopathies].
AB  - Podocytes, the visceral glomerular epithelial cells, are the postmythotic cells
      that line the outer aspects of the glomerular basement membrane. A number of
      advances have been made in recent years, linked to the discovery of single-gene
      defects in hereditary glomerular disease, which highlight the role of these cells
      in preventing proteinuria. Despite the rarity of hereditary proteinuric
      syndromes, genetic, biochemical, and structural studies of these diseases have
      made important contributions to our knowledge of how the normal glomerular filter
      works and the mechanism of proteinuria. The course of these diseases can vary;
      some patients present with severe proteinuria and congenital nephrotic syndrome,
      whereas others have only moderate proteinuria and focal segmental
      glomerulosclerosis. Regardless of its cause, the disease often progresses to end
      stage renal disease. There can be overlap between the diseases: mutations in the
      same gene can lead to different renal phenotypes. It is important to know that
      some hereditary podocytopathies respond to therapy, whereas majority does not.
      For this reason, genetic testing, which is available for some hereditary
      podocytopathies should be performed whenever possible. This review summarizes
      recent progress in the eludication of genetic causes of disease and discusses
      their implication for the understanding of the pathogenic mechanisms which can
      lead to disruption of the glomerular filtration barrier.

PMID- 20804105
TI  - [Autosomal dominant polycystic kidney disease].
AB  - Autosomal dominant polycystic kiney disease is a hereditary systemic disorder,
      characterized by the developement of cysts, mainly in the kidney and liver, also
      with gastrointestinal and cardiovascular abnormalities. It affects 4 to 6 million
      people wordwide and accounts for end-stage renal disease in 7-10% of dialysis
      patients. The genetic penetrance is 100%, all affected individuals develop renal
      cysts until 70 years of age, and because of a great renal function reserve only
      about 50% of patients develop some degree of renal failure until the age of 60.
      Autosomal dominant polycystic kiney disease is a heterogeneous disorder, from a
      clinical as well as from a genetic point of view. There are at least three genes
      responsible for the disease: PKD-1 gene localized on chromosome 16p in the
      16p13.3 segment which encodes Polycystin 1 protein similar to membrane receptor,
      PKD-2 gene localized on chromosome 4q in 4q13-23 segment which encodes Polycystin
      2 protein wery similar to voltage L type Ca++ channel as well as Na+ channel and
      PKD-3 gene of unknown localization. Specific proteins participate in regulation
      od cell proliferation, apoptosis, secretion, polarity, cell-matrix interactions
      as cell-cell interactions and lead to the developement of cystic kidney disease.
      Renal manifestations of disease include structural (cyst development), functional
      (concentration alility falls), endocrine (renin erythropoietin) abnormalities and
      extra- renal manifestations. A routine diagnostic methods are good case-history
      about cystic kidney disease in family, ultrasonographic examination of kidneys
      and computerized tomography. In therapy of autosomal dominant polycystic kiney
      disease, low protein diets may help, treatment of arterial hypertension with ACE
      inhibitors and angiotensin II receptor blockers, the vasopressin V2 antagonists
      (VSR), rapamycin and long-acting somatostatin analogue may have some benefit.

PMID- 20804106
TI  - [Autosomal recessive polycystic kidney disease and complex nephronophtisis
      medullary cystic disease].
AB  - Reseach during the past decade has led to the discovery that defects in some
      proteins that localize to primary cilia or the basal body are the main
      contributors to renal cyst development. Autosomal recessive polycystic disease
      and nephronophthisis- medullary cystic kidney disease are named ciliopathies. The
      cilium is a microtubule-based organelle that is found on most mammalian cells.
      Cilia-mediated hypothesis has evolved into the concept of cystogenesis, cilia
      bend by fluid initiate a calcium influx that prevents cyst formation. Cilia might
      sense stimuli in the cell enviroment and control cell polarity and mitosis. A new
      set of pathogenic mechanisms in renal cystic disease defined new therapeutic
      targets, control of intracellular calcium, inhibition of cAMP and down regulation
      cannonical Wnt signaling.

PMID- 20804107
TI  - Insurance credentialing. It pays to stay organized.

PMID- 20804108
TI  - Child and adolescent immunization. Current issues and updates.

PMID- 20804109
TI  - Nutrition interventions for aging healthy. Supplements set the foundation.

PMID- 20804110
TI  - Trusting your intuition. Harnessing an inner power.

PMID- 20804111
TI  - Knowledge = power.

PMID- 20804112
TI  - Development and implementation of an adolescent epilepsy transition clinic.
AB  - This article describes the collaborative development of a nurse-led transition
      clinic within the Comprehensive Epilepsy Program at the Stollery Children's
      Hospital and at the University of Alberta Hospital. Developed in 2005, our
      program has been instrumental in assisting 97 teens and their parents' transition
      from pediatric to adult epilepsy care. Through our Adolescent Epilepsy Transition
      Clinic, we address concerns expressed by teens and their parents when shifting
      from pediatric to adult healthcare services, including fear of the unknown,
      change in appointment location, loss of established relationships, and
      anticipated decrease in the quality of care posttransition. We also address
      concerns of adult and pediatric healthcare providers related to the adolescents'
      working knowledge of how their particular type of epilepsy and its management
      interact with typical adolescent developmental challenges and future career and
      lifestyle choices. The results from a process evaluation are presented and offer
      new insights for improving adolescent transition.

PMID- 20804113
TI  - Sleep in older adults with Alzheimer's disease.
AB  - Sleep in older adults with Alzheimer's disease can often be extremely fragmented,
      thus disturbing normal sleep-wake rhythms. This poor-quality sleep is challenging
      for caregivers and frequently results in admitting older adults to long-term care
      institutions. Many variables, such as genes, medications, depression, and
      environmental factors, influence sleep in persons with Alzheimer's disease.
      Interventions, such as exposure to light, melatonin therapy, sleep hygiene, and
      physical activity, are commonly used to treat or to prevent sleep problems.
      Neuroscience nurses can play an important role in assessing sleep characteristics
      and related factors, educating caregivers and staff, providing family members
      with emotional support, and conducting research.

PMID- 20804114
TI  - Alterations in serum osmolality, sodium, and potassium levels after repeated
      mannitol administration.
AB  - This study was undertaken to evaluate whether significant alterations in serum
      osmolality, [Na+], and [K+] occur after the repeated dosing of mannitol and
      whether these imbalances increased accordingly with the progress of mannitol
      application. This study was conducted by performing a retrospective medical
      record review of brain injury patients who were admitted to the neurological
      intensive care units of a university hospital located in Incheon, South Korea.
      Data on intracranial pressure and serum [Na+], [K+], and osmolality levels were
      collected from the first to the seventh day of mannitol administration. Our
      results showed that the highest rate of hyperosmolality occurred on the first day
      of mannitol administration and that subsequently its rate reduced, although it
      still maintained high (70-77%). Regarding the serum [Na+], hypernatremia was
      observed in 10% of the subjects on the first day of mannitol administration and
      in 10-21% throughout the 7-day mannitol administration period. In this study,
      hyponatremia was observed in 12.2% of our subjects on the first day of mannitol
      administration and in 9-24% throughout the 7-day period. In addition, no
      statistical differences were found between changes in the rates of hypernatremia
      and hyponatremia throughout the 7-day administration period. The most notable
      finding was the high rates of hypokalemia observed during mannitol
      administration. Hypokalemia was observed in 22% of subjects on the first day and
      continuously increased to 52.3%, and this increase was significant. On the other
      hand, the rate of hyperkalemia was almost negligible. Our findings appear to
      provide clear evidence of electrolyte imbalances after repeated mannitol
      administration. Accordingly, careful monitoring of electrolyte status is
      essential when repeated doses of mannitol are given. We recommend that the
      practice of administering repeated dose of mannitol for prophylactic purposes be
      reevaluated.

PMID- 20804115
TI  - Raising awareness of heparin-induced thrombocytopenia in subarachnoid hemorrhage.

PMID- 20804116
TI  - Symptom cluster and quality of life: preliminary evidence in multiple sclerosis.
AB  - This study examined the symptom cluster of fatigue, pain, and depression as a
      correlate of reduced quality of life (QOL) in individuals with multiple sclerosis
      (MS). The sample included 291 individuals with a definite diagnosis of MS who
      were enrolled in a 6-month longitudinal study of physical activity and QOL. The
      participants completed baseline measures of fatigue, depression, and pain and
      follow-up measures of QOL. Cluster analysis initially identified three subgroups
      differing in experiences of fatigue, depression, and pain, and analysis of
      variance then indicated that the three subgroups differed in QOL. The subgroup
      with lowest scores on all three symptoms had the highest QOL, whereas the
      subgroup with the highest scores on the symptoms had the worst QOL. Such findings
      provide preliminary support for fatigue, pain, and depression as a symptom
      cluster that correlates with reduced QOL in persons with MS.

PMID- 20804117
TI  - Benefits of quiet time for neuro-intensive care patients.
AB  - The primary mission of any intensive care unit (ICU) is to provide critically ill
      patients with high-quality care and an atmosphere in which to recuperate.
      However, all too often, the intensive environment, which is often busy, chaotic,
      and noisy, may contribute to just the opposite. Patients overstimulated with
      noise, lights, and other distractions often suffer from sleep deprivation.
      Research in medicine and nursing has shown that sleep deprivation can have
      detrimental effects on an ailing patient. Therefore, a quiet time program was
      developed in the neuro-ICU to reduce noise and light levels, with the ultimate
      goal to allow sleep. Quiet time, a period of reduced controllable noise and
      light, took place twice daily coinciding with circadian rhythms. The study
      included 50 neuro-ICU patients, 35 observed during day hours and 15 observed
      during night hours. Noise and light levels were measured at multiple locations
      before, during, and after quiet time hours. Patients' sleep behavior was recorded
      every half hour, beginning 1/2 hour before quiet time until 30 minutes after.
      Analysis of data, adjusted for multiple testing and repeated measures on
      patients, demonstrated significantly lower noise and light levels during day
      shift quiet time. In addition, patients were significantly more likely to be
      observed sleeping during day shift quiet time hours.

PMID- 20804119
TI  - Recombinant factor VIIa and the patient with neurologic bleeding: separating fact
      from fiction.
AB  - Notwithstanding its limited Food and Drug Administration-approved indications,
      rFVIIa has rapidly gained widespread use for the treatment of a variety of
      hemorrhagic conditions, including intracranial bleeding from spontaneous,
      traumatic, surgical, and coagulopathic causes. Although it appears that the drug
      only minimally increases the risk of thromboembolic events, its efficacy remains
      in question. The idea of finding a universal cure for hemorrhage in a medication
      bottle remains highly appealing, but enthusiasm for the concept is no replacement
      for evidence. Neuroscience nurses, who are the interface between patients and
      rFVIIa, need to balance hope and hype until the facts are all in.

PMID- 20804118
TI  - Standardized admission and discharge templates to improve documentation of The
      Joint Commission on Accreditation of Healthcare Organization performance markers.

PMID- 20804120
TI  - Heme as trigger and target for trioxane-containing antimalarial drugs.
AB  - Heme is not only just the binding site responsible for oxygen transport by
      hemoglobin, but it is also the prosthetic group of many different heme-containing
      enzymes, such as cytochromes P450, peroxidases, catalase, and several proteins
      involved in electron transfer. Heme plays a key role in the mechanism of action
      of many different antimalarial drugs. In degrading the host's hemoglobin, the
      malaria parasite Plasmodium and several other heme-eating parasites are faced
      with this redox-active metal complex. Heme is able to induce the toxic reductive
      cascade of molecular oxygen, which leads to the production of destructive
      hydroxyl radicals. Plasmodium detoxifies heme by converting it into a redox
      inactive iron(III) polymer called hemozoin. Artemisinin, a natural drug
      containing a biologically important 1,2,4-trioxane structure, is now the first
      line treatment for multidrug-resistant malaria. The peroxide moiety in
      artemisinin reacts in the presence of the flat, achiral iron(II)-heme; the
      mechanism does not reflect the classical "key and lock" paradigm for drugs.
      Instead, the reductive activation of the peroxide function generates a short
      lived alkoxy radical, which quickly rearranges to a C-centered primary radical.
      This radical alkylates heme via an intramolecular process to produce covalent
      heme-drug adducts. The accumulation of non-polymerizable redox-active heme
      derivatives, a consequence of heme alkylation, is thought to be toxic for the
      parasite. The alkylation of heme by artemisinin has been demonstrated in malaria
      infected mice, indicating that heme is acting as the trigger and target of
      artemisinin. The alkylation of heme by artemisinin is not limited to this natural
      compound: the mechanism is invoked for a large number of antimalarial
      semisynthetic derivatives. Synthetic trioxanes or trioxolanes also alkylate heme,
      and their alkylation ability correlates well with their antimalarial efficacy. In
      addition, several reports have demonstrated the cytotoxicity of artemisinin
      derivatives toward several tumor cell lines. Deoxy analogues were just one
      fiftieth as active or less, showing the importance of the peroxide bridge. The
      involvement of heme in anticancer activity has thus also been proposed. The
      anticancer mechanism of endoperoxide-containing molecules, however, remains a
      challenging area, but one that offers promising rewards for research success.
      Although it is not a conventional biological target, heme is the master piece of
      the mechanism of action of peroxide-containing antimalarial drugs and could well
      serve as a target for future anticancer drugs.

PMID- 20804121
TI  - Quaternary ammonium compounds in urban estuarine sediment environments--a class
      of contaminants in need of increased attention?
AB  - The distributions of wastewater-derived quaternary ammonium compounds (QACs) were
      determined in surficial sediments (n = 47) collected from the urbanized lower
      Hudson River basin. The most abundant class of QACs were dialkyldimethylammonium
      compounds (DADMACs, with C8 to C18 carbon chain lengths; median SigmaDADMAC = 26
      MUg/g), followed by benzylalkyldimethylammonium compounds (BAC, C12-C18; 1.5
      MUg/g), and alkyltrimethylammonium compounds (ATMAC, primarily C16 and C18; 0.52
      MUg/g). The concentrations of total QACs are higher than those of other
      conventional organic contaminants determined on the same samples (e.g., median
      SigmaPAH level of 2.1 MUg/g). Comparatively high concentrations, correlations
      with sewage derived contaminants, and the relatively constant compositions of
      QACs observed over large areas suggest that many sediment-sorbed QACs can be
      relatively persistent in receiving waters. Unusually large concentration
      dependent sorption is considered as a mechanism that likely affects persistence
      of these intrinsically biodegradable chemicals under field conditions. There has
      been comparatively little field-based research on these classes of cationic
      surfactants; given the levels of QACs observed here, it is suggested that further
      investigation is warranted.

PMID- 20804122
TI  - Occurrence of alkyltrimethylammonium compounds in urban estuarine sediments:
      behentrimonium as a new emerging contaminant.
AB  - The distribution of alkyltrimethylammonium compounds (ATMAC), cationic
      surfactants used in a wide variety of applications, has been determined in
      sediments from Jamaica Bay (NY). Total concentrations in surficial sediments
      collected between 1998 and 2008 ranged from 361 to 6750 ng/g. The highest values
      were found in samples from a deeper basin directly affected by treated wastewater
      discharges. Behentrimonium, a mixture dominated by a homologue having 22 carbon
      atoms in its alkyl chain (ATMAC 22), was identified for the first time using time
      of-flight mass spectrometry and accounted for approximately 80% of the total
      ATMAC in recent sediment samples. Analyses of a dated sediment core and
      subsequent surface grab samples revealed an exponential increase in concentration
      over the last three decades with a doubling time of 3.9 years. Similar temporal
      trends were seen in surface samples from other sites in Jamaica Bay and Newton
      Creek (NY), another site greatly influenced by wastewater discharges. This
      dramatic increase in ATMAC 22 reflects greater use of behentrimonium and likely
      replacement of other products containing other ATMAC homologues in personal care
      products. Further monitoring is recommended to assess the environmental risk and
      fate of this persistent emerging contaminant.

PMID- 20804123
TI  - Effects of kernel breakage and fermentation on corn germ integrity and oil
      quality.
AB  - To investigate the ability of corn germ to withstand the fuel ethanol
      fermentation process without major damage to germ integrity and germ oil quality,
      five treatments were designed to explore degerming before fermentation (front
      end) and after fermentation (tail-end), and the feasibility of breaking the
      kernel with minimum shear forces (wet-split). Germ from low-shear (wet-split)
      tail-end degerming maintained its integrity during the process. The wet-grind
      pretreatment caused 22% germ damage, and the subsequent fermentation caused 18%
      additional germ damage. The germ recovered after fermentation showed physical
      strength similar to that of those isolated by wet means before fermentation. The
      oils extracted from the tail-end germ fractions had the same low free fatty acid
      (FFA) content (2%) and similar low peroxide value (2 meq/kg) as those extracted
      at the front end. The good oil quality of the tail-end germ fraction was
      attributed to excellent germ integrity. The oil recovered after traditional dry
      grind ethanol production was highly deteriorated, with 22% FFAs and 9 meq/kg
      peroxide value because the germ was broken into small pieces during dry grinding.
      So long as kernel-breakage or size-reduction pretreatments are conducted to
      retain intact germs or keep them in large pieces before fermentation, the germ
      can survive the cooking, starch hydrolysis, and yeast metabolism during the
      ethanol fermentation process. These findings lay a foundation for developing new
      degerming strategies where the germ can be isolated during or after fermentation,
      which could be easily integrated into the conventional dry-grind corn ethanol
      process.

PMID- 20804124
TI  - Antimicrobial activity of lipophilic avian eggshell surface extracts.
AB  - The avian eggshell cuticle is the waxy outermost layer of the mineralized
      eggshell in direct contact with the environment. In this study, lipophilic
      eggshell surface extracts from three domestic species were evaluated for their
      antimicrobial activity. Chicken and goose extracts demonstrated potent
      bactericidal activity against both Gram-positive and Gram-negative bacteria,
      while activity could not be detected for duck eggshell surface extracts. Using
      the chicken as a model species, evaluation of albumen, fecal material, and
      uropygial gland extracts eliminated these as a potential source of the observed
      activity. Results suggest that lipophilic components are incorporated into the
      egg during its formation and play a role in antimicrobial defense. This study
      represents the first successful extraction and evaluation of lipophilic
      antimicrobial components from the avian egg.

PMID- 20804125
TI  - Phenolic contents and antioxidant activities of major Australian red wines
      throughout the winemaking process.
AB  - Three Australian red wine types (Shiraz, Cabernet Sauvignon, and Merlot) were
      analyzed for antioxidant activity and a range of phenolic component contents
      using various spectral methods. More than half of the total phenolic compounds
      were tannins, whereas monomeric anthocyanins and flavonols were present in much
      lesser amounts (<10%). The evolution of phenolic contents and the respective
      antioxidant activities in wine samples from all stages of winemaking showed
      progressive changes toward those of commercial wines. The antioxidant activity of
      the wines in DPPH and ABTS assays was positively correlated with total phenolic
      contents and tannins. Comparisons of the three wine varieties based on their
      individual phenolic component groups and antioxidant activities showed limited
      differences between the different varieties. However, when all of the variables
      were combined in a principal component analysis, variety differentiation was
      observed. The three varieties of red wines all contained similar and high
      concentrations of antioxidants despite differences in grape variety/maturity and
      winemaking process, suggesting that related health benefits would accrue from all
      of the red wines studied.

PMID- 20804126
TI  - Acceptor energy level control of charge photogeneration in organic donor/acceptor
      blends.
AB  - In this paper we focus upon the role of interfacial energetics in influencing the
      separation of charge transfer states into dissociated charge carriers in organic
      donor/acceptor blend films. In particular, we undertake transient optical studies
      of films comprising regioregular poly(3-hexylthiophene) (P3HT) blended with a
      series of perylene-3,4:9,10-tetracarboxydiimide (PDI) electron acceptors. For
      this film series, we observe a close correlation between the PDI electron
      affinity and the efficiency of charge separation. This correlation is discussed
      in the context of studies of charge photogeneration for other organic
      donor/acceptor blend films, including other polymers, blend compositions, and the
      widely used electron acceptor 3'-phenyl-3'H-cyclopropa[1,9](C(60)
      I(h))[5,6]fullerene-3'-butanoic acid methyl ester (PCBM).

PMID- 20804127
TI  - Antihyperglycemic effect of a caffeamide derivative, KS370G, in normal and
      diabetic mice.
AB  - The antihyperglycemic actions of caffeamide derivatives, especially KS370G, in
      normal ICR, streptozotocin-induced diabetic (T1DM) and diet-induced diabetic
      (T2DM) mice were investigated in this study. Oral administration of the compound
      decreased the plasma glucose levels in both normal and diabetic mice, and
      appeared to be in a dose-dependent manner in normal and diet-induced type 2
      diabetic mice. It was found that KS370G could stimulate the release of insulin in
      both normal and T2DM mice, and a dose of 1 mg per kg KS370G could significantly
      attenuate the increase of plasma glucose induced by an intraperitoneal glucose
      challenge test in normal and diabetic mice. Similar treatment with KS370G
      significantly increased glycogen content in both liver and skeletal muscle.
      Hence, the hypoglycemic effect of KS370G in normal and diabetic mice could be
      attributed to the stimulation of insulin release and the increase of glucose
      utilization.

PMID- 20804128
TI  - Proteomic and bioinformatic analysis of the root-knot nematode Meloidogyne hapla:
      the basis for plant parasitism.
AB  - On the basis of the complete genome sequence of the root-knot nematode Melodogyne
      hapla, we have deduced and annotated the entire proteome of this plant-parasite
      to create a database of 14,420 proteins. We have made this database, termed
      HapPep3, available from the Superfamily repository of model organism proteomes
      (http://supfam.mrc-lmb.cam.ac.uk/SUPERFAMILY). To experimentally confirm the
      HapPep3 assignments using proteomics, we applied a data-independent LC/MS(E)
      analysis to M. hapla protein extracts fractionated by SDS-PAGE. A total of 516
      nonredundant proteins were identified with an average of 9 unique peptides
      detected per protein. Some proteins, including examples with complex gene
      organization, were defined by more than 20 unique peptide matches, thus,
      providing experimental confirmation of computational predictions of intron/exon
      structures. On the basis of comparisons of the broad physicochemical properties
      of the experimental and computational proteomes, we conclude that the identified
      proteins reflect a true and unbiased sampling of HapPep3. Conversely, HapPep3
      appears to broadly cover the protein space able to be experimentally sampled. To
      estimate the false discovery rate, we queried human, plant, and bacterial
      databases for matches to the LC/MS(E)-derived peptides, revealing fewer than 1%
      of matches, most of which were to highly conserved proteins. To provide a
      functional comparison of the acquired and deduced proteomes, each was subjected
      to higher order annotation, including comparisons of Gene Ontology, protein
      domains, signaling, and localization predictions, further indicating concordance,
      although those proteins that did deviate seem to be highly significant.
      Approximately 20% of the experimentally sampled proteome was predicted to be
      secreted, and thus potentially play a role at the host-parasite interface. We
      examined reference pathways to determine the extent of proteome similarity of M.
      hapla to that of the free-living nematode, Caenorhabditis elegans, revealing
      significant similarities and differences. Collectively, the analyzed protein set
      provides an initial foundation to experimentally dissect the basis of plant
      parasitism by M. hapla.

PMID- 20804129
TI  - High-dielectric polymer composite materials from a series of mixed-metal
      phenylphosphonates, ATi(C6H5PO3)3 for dielectric energy storage.
AB  - We report the preparation of new polymer composite dielectric materials for
      energy storage applications. New layered 1:1 mixed A+2/Ti4+ metal
      phenylphosphonates, ATi(O3PC6H5)3, A=Mg, Ca, Sr, Ba, and Pb, have been prepared
      via a melt route, in which mixed metal oxides, ATiO3, were reacted with molten
      phenyl phosphonic acid. The mixed-metal phosphonates were combined with
      polystyrene (PS) via a solution route and cast as thin films for dielectric
      permittivity measurements. The ATi(O3PC6H5)3-PS composites exhibit a substantial
      enhancement in the dielectric permittivity as a function of weight loading
      relative to the parent ATiO3-PS composites. For both ATiO3-PS and ATi(O3PC6H5)3
      PS, the composites' dielectric permittivity increases with A cation
      polarizability. Unusually large increases for 40 wt% ATi(O3PC6H5)3-PS composites
      (A=Sr, Ba, and Pb) indicate permittivity enhancement that goes beyond the effect
      of varying filler composition.

PMID- 20804130
TI  - Elemental composition of nanoparticles with the nano aerosol mass spectrometer.
AB  - The nano aerosol mass spectrometer (NAMS) irradiates individual, size selected
      nanoparticles with a high energy laser pulse to generate a mass spectrum
      consisting of multiply charged atomic ions. The elemental composition of the
      particle is determined from the ion signal intensities of each element, which
      requires deconvoluting isobaric ion signals at 4 m/z (O(4+) and C(3+)) and at 8
      m/z (O(2+) and S(4+)). A method to deconvolute these ion signals using sucrose
      and ammonium sulfate as calibrants is presented. The approach is based on the
      assumption that the charge state distribution of a given element is independent
      of the chemical form of that element in the particle. Relative to previously
      reported methodology, the new approach permits accurate and precise determination
      of sulfur, which is crucial for interpretation of ambient nanoparticle data sets.
      With this approach, the differences between expected and measured elemental
      ratios of C, O, N, and S for a variety of test particles were generally much less
      than 10%, although a difference as high as 16% was observed.

PMID- 20804131
TI  - Direct construction of imino-pyrrolidine-thione scaffold via isocyanide-based
      multicomponent reaction.
AB  - A novel and efficient method has been developed for the direct construction of
      imino-pyrrolidine-thione scaffold via the coupling of isocyanides, heterocyclic
      thiols, and gem-dicyano olefins. Smiles rearrangement followed by intramolecular
      cyclization leads directly to formation of the core structure. A water
      acceleration effect is observed, promoting most of the reactions to go to
      completion within a short reaction time.

PMID- 20804132
TI  - Generation of simplified protein Raman spectra using three-color picosecond
      coherent anti-stokes Raman spectroscopy.
AB  - The well-known and prominent marker bands of aromatic amino acids in Raman
      spectra of protein and peptide films are revisited in the frequency and time
      domains using three-color picosecond coherent anti-Stokes Raman spectroscopy
      (CARS). We show here that control of the probe delay allows the narrow width/long
      lifetime states to be observed free not only from nonresonant background and
      fluorescence contamination but also free from the spectral congestion that arises
      from the complex background of spectrally broader (shorter lifetime) vibrational
      modes. The reasonable limits of detection obtained indicate that such CARS
      methods may be useful for quantitative analysis of protein composition.

PMID- 20804133
TI  - Pseudo-emulsion membrane strip dispersion (PEMSD) pertraction of chromium(VI)
      using CYPHOS IL101 ionic liquid as carrier.
AB  - The transport of chromium(VI) from hydrochloric acid medium by pseudoemulsion
      membrane strip dispersion (PEMSD), using CYPHOS IL101 (phosphonium salt) as
      ionophore, is investigated under various experimental variables in the feed phase
      [hydrodynamic conditions, concentration of Cr(VI) (0.01-1 g/L), concentration of
      HCl (0.01-1M)], in the organic phase [carrier concentration (1-10% v/v)], and in
      the strip phase (stripping agent). Other variables investigated were the volume
      organic/strip phase ratios in the pseudoemulsion phase and also the type of
      membrane support. Under given experimental conditions, i.e., [Cr(VI)](0) = 0.01
      g/L and [HCl](0) = 0.01 M in the feed phase and organic solution of 10% v/v
      CYPHOS IL101 in cumene, extractions exceeding 95% are obtained, and it is
      possible to strip using 1 M NaoH solution (also with recoveries in the 60%
      range). The performance of the system is also compared against other membrane
      operational configurations.

PMID- 20804134
TI  - Household water treatment and the millennium development goals: keeping the focus
      on health.
AB  - Waterborne diseases such as diarrhea are a major killer in low-income settings,
      particularly of young children. For those without access to safe drinking water,
      household water treatment, such as boiling, chlorinating, and filtering water in
      the home, when combined with safe storage (HWTS) can significantly improve water
      quality and prevent disease, thereby contributing to the child survival and other
      health priorities encompassed within the Millennium Development Goals (MDGs).
      There is uncertainly, however, about whether HWTS should count toward the MDG
      water target, which promotes "sustainable access to safe drinking water". This
      paper reviews the relevant research and concludes that it should not. Although
      HWTS can significantly improve water quality, it does not improve water quantity
      and access-key aspects of the MDG water target that are essential for optimal
      improvements in health and development. A policy that excludes HWTS from the MDG
      water target will discourage governments from diverting scarce public resources
      from comprehensive and long-term improvements in water supplies. At the same
      time, the health-oriented MDGs provide a sufficient case for scaling up effective
      and appropriate HWTS among target populations. Moreover, a health-based strategy
      for HWTS will help ensure that promotion of the intervention is driven by
      measurable improvements in outcomes rather than inputs, thus encouraging advances
      in both hardware and programmatic delivery that will make HWTS more effective,
      appropriate, and accessible to vulnerable populations.

PMID- 20804135
TI  - Effect of bare and coated nanoscale zerovalent iron on tceA and vcrA gene
      expression in Dehalococcoides spp.
AB  - Nanoscale zerovalent iron (NZVI) can be used to dechlorinate trichloroethylene
      (TCE) in contaminated aquifers. Dehalococcoides spp. is the only microbial genus
      known to dechlorinate TCE to ethene as a respiratory process. However, little is
      known about how NZVI affects the expression of genes coding for reductive
      dechlorination. We examined a high-rate TCE-dechlorinating mixed culture which
      contains organisms similar to known Dehalococcoides to study the effects of NZVI
      on the expression of two model genes coding for reductive dehalogenases (tceA and
      vcrA). A novel pretreatment approach, relying on magnetic separation of NZVI
      prior to reverse transcription qPCR (to avoid RNA adsorption by NZVI), was
      developed and used with relative quantification (relative to 16S rRNA as
      endogenous housekeeping gene) to quantify reductive dehalogenase gene expression.
      Both tceA and vcrA were significantly down-regulated (97- and 137-fold,
      respectively) relative to baseline (time 0) conditions after 72-h exposure to
      chlorinated ethenes (0.12 +/- 0.03 mg/L cis-DCE, 0.69 +/- 0.11 mg/L t-DCE, and
      0.54 +/- 0.16 mg/L VC) and bare-NZVI (1 g-NZVI/L). However, coating NZVI with an
      olefin maleic acid copolymer (a common approach to enhance its mobility in
      aquifers) overcame this significant inhibitory effect, and both tceA and vcrA
      were up-regulated (3.0- and 3.5-fold, respectively) after 48-h exposure. Thus,
      NZVI coating might enhance the expression of dechlorinating genes and the
      concurrent or sequential participation of Dehalococcoides spp. in the remediation
      process.

PMID- 20804136
TI  - Pore-scale study of transverse mixing induced CaCO3 precipitation and
      permeability reduction in a model subsurface sedimentary system.
AB  - A microfluidic pore structure etched into a silicon wafer was used as a two
      dimensional model subsurface sedimentary system (i.e., micromodel) to study
      mineral precipitation and permeability reduction relevant to groundwater
      remediation and geological carbon sequestration. Solutions containing CaCl(2) and
      Na(2)CO(3) at four different saturation states (Omega = [Ca(2+)][CO(3)(2
      )]/K(spCaCO(3))) were introduced through two separate inlets, and they mixed by
      diffusion transverse to the main flow direction along the center of the
      micromodel resulting in CaCO(3) precipitation. Precipitation rates increased and
      the total amount of precipitates decreased with increasing saturation state, and
      only vaterite and calcite crystals were formed (no aragonite). The relative
      amount of vaterite increased from 80% at the lowest saturation state (Omega(v) =
      2.8 for vaterite) to 95% at the highest saturation state (Omega(v) = 4.5).
      Fluorescent tracer tests conducted before and after CaCO(3) precipitation
      indicate that pore spaces were occluded by CaCO(3) precipitates along the
      transverse mixing zone, thus substantially reducing porosity and permeability,
      and potentially limiting transformation from vaterite to the more stable calcite.
      The results suggest that mineral precipitation along plume margins can decrease
      both reactant mixing during groundwater remediation, and injection and storage
      efficiency during CO(2) sequestration.

PMID- 20804137
TI  - Throwing fuel on the fire: synergistic effects of excessive nitrogen inputs and
      global warming on harmful algal blooms.

PMID- 20804138
TI  - Carboxylic acid appended dipyrrin for the formation of a hexanuclear
      iridium/copper paddlewheel complex.
AB  - Reaction of a heteroleptic cyclometalated iridium complex incorporating a
      carboxylic acid appended dipyrrin with copper acetate leads to the formation of a
      hexanuclear species with the paddlewheel structure.

PMID- 20804139
TI  - Slow magnetic relaxation and charge-transfer in cyano-bridged coordination
      clusters incorporating [Re(CN)(7)](3-/4-).
AB  - Treatment of the cyanometalate building unit [Re(CN)(7)](3-) with
      [(PY5Me(2))M(MeCN)](2+) (M = Co, Ni, Cu) affords a series of pentanuclear
      clusters of formulas [(PY5Me(2))(4)M(4)Re(CN)(7)](5+) (M = Co, Ni, Cu) and
      [(PY5Me(2))(4)Cu(4)Re(CN)(7)](4+). Single crystal X-ray diffraction analyses of
      the clusters reveal a star-like structure in which four [(PY5Me(2))M](2+)
      moieties are linked to a central [Re(CN)(7)](3-) unit via bridging cyanide
      ligands. An intramolecular Co(II) -> Re(IV) charge-transfer accompanies the
      formation of the Co(II)(4)Re(IV) cluster, giving a Co(II)(3)Co(III)Re(III)
      species. Spectroelectrochemical methods and irradiation experiments are used to
      characterize the metal-metal charge-transfer bands of this compound. A rhenium
      based thermally induced one-electron reduction is observed for the
      Cu(II)(4)Re(IV) cluster to give a Cu(II)(4)Re(III) complex; however, this
      reduction may be forestalled at low temperature. Finally, magnetic measurements
      reveal intracluster ferromagnetic exchange coupling, strong uniaxial magnetic
      anisotropy, and slow magnetic relaxation in the Ni(II)(4)Re(IV) and
      Cu(II)(4)Re(IV) clusters.

PMID- 20804140
TI  - Pd-catalyzed oxidative cross-coupling of perfluoroarenes with aromatic
      heterocycles.
AB  - A straightforward and practical method for direct Pd(OAc)(2)-catalyzed oxidative
      cross-coupling of electron-deficient perfluoroarenes with aromatic heterocycles
      has been developed. Because of its low catalyst loading (2.5 mol %), high
      reaction efficiency, good chemo- and regioselectivity, and excellent functional
      group compatibility, this protocol provides a useful and operationally simple
      access to perfluoroarene-thiophene structures of interest in functional materials
      for electronic devices.

PMID- 20804141
TI  - Quinacridone-based molecular donors for solution processed bulk-heterojunction
      organic solar cells.
AB  - New soluble quinacridone-based molecules have been developed as electron donor
      materials for solution-processed organic solar cells. By functionalizing the
      pristine pigment core of quinacridone with solubilizing alkyl chains and light
      absorbing/charge transporting thiophene units, i.e., bithiophene (BT) and
      thienylbenzo[c][1,2,5]thiadiazolethienyl (BTD), we prepared a series of
      multifunctional quinacridone-based molecules. These molecular donors show intense
      absorption in the visible spectral region, and the absorption range and intensity
      are well-tuned by the interaction between the quinacridone core and the
      incorporated thiophene units. The thin film absorption edge extends with the
      expansion of molecular conjugation, i.e., 552 nm for N,N'-di(2
      ethylhexyl)quinacridone (QA), 592 nm for 2,9-Bis(5'-hexyl-2,2'-bithiophene)-N,N'
      di(2-ethylhexyl)quinacridone (QA-BT), and 637 nm for 4-(5-hexylthiophen-2-yl)-7
      (thiophen-2-yl)benzo[c][1,2,5]thiadiazole (QA-BTD). The change of molecular
      structure also influences the electrochemical properties. Observed from cyclic
      voltammetry measurements, the oxidation and reduction potentials (vs ferrocene)
      are 0.7 and -1.83 V for QA, 0.54 and -1.76 V for QA-BT, and 0.45 and -1.68 V for
      QA-BTD. Uniform thin films can be generated from both single component molecular
      solutions and blend solutions of these molecules with [6,6]-phenyl C70-butyric
      acid methyl ester (PC70BM). The blend films exhibit space-charge limited current
      (SCLC) hole mobilities on the order of 1*10(-4) cm(2) V(-1) S(-1). Bulk
      heterojunction (BHJ) solar cells using these soluble molecules as donors and
      PC70BM as the acceptor were fabricated. Power conversion efficiencies (PCEs) of
      up to 2.22% under AM 1.5 G simulated 1 sun solar illumination have been achieved
      and external quantum efficiencies (EQEs) reach as high as ~45%.

PMID- 20804142
TI  - Theoretical study of excited states of pyrazolate- and pyridinethiolate-bridged
      dinuclear platinum(II) complexes: relationship between geometries of excited
      states and phosphorescence spectra.
AB  - Dinuclear platinum(II) complexes [Pt(2)(MU-pz)(2)(bpym)(2)](2+) (1; pz =
      pyrazolate and bpym = 2,2'-bipyrimidine) and [Pt(2)(MU-pyt)(2)(ppy)(2)] (2; pyt =
      pyridine-2-thiolate and Hppy = 2-phenylpyridine) were theoretically investigated
      with density functional theory (DFT) to clarify the reasons why the
      phosphorescence of 1 is not observed in the acetonitrile (CH(3)CN) solution at
      room temperature (RT) but observed in the solid state at RT and why the
      phosphorescence of 2 is observed in both the CH(3)CN solution and the solid state
      at RT. The S(1) and T(1) states of 1 in the CH(3)CN solution are assigned as a
      metal-metal-to-ligand charge-transfer (MMLCT) excited state. Their geometries are
      C(2v) symmetrical, in which spin-orbit interaction between the S(1) and T(1)
      excited states is absent because the direct product of irreducible
      representations of the singly occupied molecular orbitals (SOMOs) of these
      excited states and the orbital angular momentum (l) operator involved in the
      Hamiltonian for spin-orbit interaction does not belong to the a(1)
      representation. As a result, the S(1) -> T(1) intersystem crossing hardly occurs,
      leading to the absence of T(1) -> S(0) phosphorescence in the CH(3)CN solution at
      RT. In the solid state, the geometry of the S(1) state does not reach the global
      minimum but stays in the C(1)-symmetrical local minimum. This S(1) excited state
      is assigned as a mixture of the ligand-centered pi-pi* excited state and the
      metal-to-ligand charge-transfer excited state. Spin-orbit interaction between the
      S(1) and T(1) excited states operates to induce the S(1) -> T(1) intersystem
      crossing because the direct product of the irreducible representations of the
      SOMOs of these excited states and the l operator belongs to the "a"
      representation. As a result, T(1) -> S(0) phosphorescence occurs in the solid
      state. In 2, the S(1) and T(1) excited states are assigned as the MMLCT excited
      state. Their geometries are C(2)-symmetrical in both the CH(3)CN solution and the
      solid state, in which spin-orbit interaction between the S(1) and T(1) states
      operates to induce the S(1) -> T(1) intersystem crossing because the direct
      product of the irreducible representations of the SOMOs and the l operator
      belongs to the "a" representation. Thus, T(1) -> S(0) phosphorescence occurs in
      both the CH(3)CN solution and the solid state at RT, unlike 1.

PMID- 20804143
TI  - Self-assembly of organic monolayers as protective and conductive bridges for
      nanometric surface-mount applications.
AB  - In this work, we present a novel surface-mount placement process that could
      potentially overcome the inadequacies of the currently used stencil-printing
      technology, when applied to devices in which either their lateral and/or their
      horizontal dimensions approach the nanometric scale. Our novel process is based
      on the "bottom-up" design of an adhesive layer, operative in the
      molecular/nanoscale level, through the use of self-assembled monolayers (SAMs)
      that could form protective and conductive bridges between pads and components. On
      the basis of previous results, 1,4-phenylene diisocyanide (PDI) and terephthalic
      acid (TPA) were chosen to serve as the best candidates for the achievement of
      this goal. The quality and stability of these SAMs on annealed Cu surfaces
      (Rrms=0.15-1.1 nm) were examined in detail. Measurements showed that the SAMs of
      TPA and PDI molecules formed on top of Cu substrates created thermally stable
      organic monolayers with high surface coverage (~90%), in which the molecules were
      closely packed and well-ordered. Moreover, the molecules assumed a standing-up
      phase conformation, in which the molecules bonded to the Cu substrate through one
      terminal functional group, with the other terminal group residing away from the
      substrate. To examine the ability of these monolayers to serve as "molecular
      wires," i.e., the capability to provide electrical conductivity, we developed a
      novel fabrication method of a parallel plate junction (PPJ) in order to create
      symmetric Cu-SAM-Cu electrical junctions. The current-bias measurements of these
      junctions indicated high tunneling efficiency. These achievements imply that the
      SAMs used in this study can serve as conductive molecular bridges that can
      potentially bind circuital pads/components.

PMID- 20804144
TI  - Transition state analysis of thymidine hydrolysis by human thymidine
      phosphorylase.
AB  - Human thymidine phosphorylase (hTP) is responsible for thymidine (dT)
      homeostasis, and its action promotes angiogenesis. In the absence of phosphate,
      hTP catalyzes a slow hydrolytic depyrimidination of dT yielding thymine and 2
      deoxyribose (dRib). Its transition state was characterized using multiple kinetic
      isotope effect (KIE) measurements. Isotopically enriched thymidines were
      synthesized enzymatically from glucose or (deoxy)ribose, and intrinsic KIEs were
      used to interpret the transition state structure. KIEs from [1'-(14)C]-, [1
      (15)N]-, [1'-(3)H]-, [2'R-(3)H]-, [2'S-(3)H]-, [4'-(3)H]-, and [5'-(3)H]dTs
      provided values of 1.033 +/- 0.002, 1.004 +/- 0.002, 1.325 +/- 0.003, 1.101 +/-
      0.004, 1.087 +/- 0.005, 1.040 +/- 0.003, and 1.033 +/- 0.003, respectively.
      Transition state analysis revealed a stepwise mechanism with a 2-deoxyribocation
      formed early and a higher energetic barrier for nucleophilic attack of a water
      molecule on the high energy intermediate. An equilibrium exists between the
      deoxyribocation and reactants prior to the irreversible nucleophilic attack by
      water. The results establish activation of the thymine leaving group without
      requirement for phosphate. A transition state constrained to match the intrinsic
      KIEs was found using density functional theory. An active site histidine (His116)
      is implicated as the catalytic base for activation of the water nucleophile at
      the rate-limiting transition state. The distance between the water nucleophile
      and the anomeric carbon (r(C-O)) is predicted to be 2.3 A at the transition
      state. The transition state model predicts that deoxyribose adopts a mild 3'-endo
      conformation during nucleophilic capture. These results differ from the concerted
      bimolecular mechanism reported for the arsenolytic reaction (Birck, M. R.;
      Schramm, V. L. J. Am. Chem. Soc. 2004, 126, 2447-2453).

PMID- 20804145
TI  - Electron paramagnetic resonance studies of nitrosyl and thionitrosyl and density
      functional theory studies of nitrido, nitrosyl, thionitrosyl, and selenonitrosyl
      complexes of chromium.
AB  - The novel S = 1/2 thionitrosyl complexes Cr(NS)(CN)(5)(3-), Cr(NS)(dmso)(5)(2+),
      and Cr(NS)(nmf)(5)(2+) (dmso = dimethyl sulfoxide, nmf = N-methylformamide) have
      been prepared, and their optical and electron paramagnetic resonance (EPR)
      spectra were studied. The values of the isotropic and anisotropic hyperfine and
      superhyperfine coupling constants A((53)Cr), A((14)N), and A((13)C) and of g were
      determined from the EPR spectra at room temperature and at 66 K. The values of
      A(?) and A(iso) in the thionitrosyl complexes were slightly higher than in the
      analogous nitrosyl complexes. A common feature in the optical absorption spectra
      of the thionitrosyl complexes in solution at 298 K is an absorption band around
      600 nm with a vibronic structure whereas such a band is located around 450 nm in
      the analogous nitrosyl complexes. Density functional theory (DFT) studies of the
      series of complexes Cr(N)(H(2)O)(5)(2+), Cr(NO)(H(2)O)(5)(2+),
      Cr(NS)(H(2)O)(5)(2+), and Cr(NSe)(H(2)O)(5)(2+) show that the unpaired electron
      resides in a metal-based d(xy) orbital and that the electronic structure in the
      equatorial plane is similar in all four complexes and similar to Cr(3+). The
      sigma donating ability was found in the order N(3-) ? NO < NS ~ NSe and the pi
      accepting ability in the order NO > NS ~ NSe. Time dependent DFT calculations
      gave in all four complexes a d(x(2)-y(2)) <- d(xy) transition energy around 17
      500 cm(-1).

PMID- 20804146
TI  - Analysis of the bromate-sulfite-ferrocyanide pH oscillator using the particle
      filter: toward the automated modeling of complex chemical systems.
AB  - This study was aimed at identifying a quantitatively accurate reaction model of
      the bromate-sulfilte-ferrocyanide (BSF) pH oscillator by using the simulation
      based model estimation algorithm known as the particle filter. The Rbai-Kaminaga
      Hanazaki (RKH) model proposed for the BSF system was extended by adding the
      protonation equilibrium of SO42-, for which the particle filter analysis was
      carried out to optimize the rate constants involved with reference to the
      measured pH oscillation data. The extended RKH model with the optimized rate
      constants almost completely reproduced the measured pH oscillations and the state
      diagram, showing the validity of the present analysis. Chemical oscillators such
      as the BSF system show drastic switching of the dominant reaction path, which
      strongly disturbs the convergence of the rate constants if the objective function
      is defined in a conventional manner to reflect only a single time step datum. In
      this study, the objective function was defined as the residual sum of squares
      with respect to pH taken over an interval longer than one oscillatory period, so
      that all of the relevant reaction steps can contribute to the objective function.
      This is the first report which exemplifies the effectiveness of the particle
      filter in the analysis of real complex chemical systems.

PMID- 20804147
TI  - In vitro studies of DNA damage caused by tricyclic antidepressants: a role of
      peroxidase in the side effects of the drugs.
AB  - Studies show that tricyclic antidepressants prescribed for migraines, anxiety,
      and child enuresis have numerous adverse effects in living cells. One of the
      undesired outcomes observed under treatment with these drugs is DNA damage.
      However, the mechanisms underlying damage have yet to be elucidated. We performed
      in vitro studies of the DNA damage caused by four tricyclic antidepressants:
      imipramine, amitriptyline, opipramol, and protriptyline. We focused particularly
      on the DNA damage aided by peroxidases. As a model of a peroxidase, we used
      horseradish peroxidase (HRP). At pH 7, reactions of HRP with excess hydrogen
      peroxide and imipramine yielded an intense purple color and a broad absorption
      spectrum with the maximum intensity at 522 nm. Reactions performed between DNA
      and imipramine in the presence of H(2)O(2) and HRP resulted in the disappearance
      of the DNA band. In the case of the other three drugs, this effect was not
      observed. Extraction of the DNA from the reaction mixture indicated that DNA is
      degraded in the reaction between imipramine and H(2)O(2) catalyzed by HRP. The
      final product of imipramine oxidation was identified as iminodibenzyl. We
      hypothesize that the damage to DNA was caused by an imipramine reactive
      intermediate.

PMID- 20804148
TI  - Simultaneous two-hydrogen transfer as a mechanism for efficient CO(2) reduction.
AB  - Two-hydrogen transfer (simultaneous protic and hydridic hydrogen transfer) is
      examined as a potentially efficient mechanism for the selective reduction of
      CO(2) to methanol. High-level ab initio CCSD(T) coupled-cluster theory
      simulations of ammonia-borane (AB), which contains both protic and hydridic
      hydrogen, show the effectiveness of this mechanism. AB demonstrates how
      simultaneous two-hydrogen transfer is kinetically efficient because (1) two
      hydrogen transfer avoids high-energy single-electron-reduced intermediates, (2)
      the CO(2)'s HOMO is protonated while the LUMO is concurrently reduced by a
      hydride, and (3) complementary charge polarities around the six-membered-ring
      transition-state structures stabilize the transition states. This study suggests
      that an effective mechanism for the reduction of CO(2) to methanol proceeds
      through three two-hydrogen-transfer steps and that suitable catalysts should be
      developed that exploit two-hydrogen transfer without the use of AB.

PMID- 20804149
TI  - Further purification of industrial quartz by much milder conditions and a
      harmless method.
AB  - A much "greener" and harmless leaching method for removing impurity aluminum
      further from industrial quartz sands by very dilute mixed acids has been
      presented. With the help of supersonic, the percentage of removal aluminum
      reached up to 52.5%/53%, that is, 17.4 ppm/17.7 ppm at 30  degrees C/80  degrees
      C, respectively. These results are 4.4/4.7 ppm lower than that supplied by a
      world famous quartz sands supplier, and the leaching conditions are much milder
      compared with other comparable methods: the concentration of hydrogen chloride in
      the mixed acid is only 10% of the others, the leaching temperature is much lower;
      at the same time, the operating time is only 13-20% of the others, thereby
      pollution of industrial strong acids and thermo-scattering is reduced
      substantially.

PMID- 20804150
TI  - One-pot desulfurative-fluorination-bromination. Synthesis of 2,5-dibromo-3-(1,1
      difluoroalkyl)thiophenes.
AB  - A unique one-pot, high-yield desulfurative-fluorination-bromination reaction
      which leads to the synthesis of 2,5-dibromo-3-(1,1-difluoroalkyl)thiophenes is
      reported. A single dithiolane reactant can be used to produce both 2,5-dibromo-3
      (1,1-difluoroalkyl)thiophene and 3-(1,1-difluoroalkyl)thiophene with longer alkyl
      chains.

PMID- 20804151
TI  - Monanchocidin: a new apoptosis-inducing polycyclic guanidine alkaloid from the
      marine sponge Monanchora pulchra.
AB  - Monanchocidin (1), a guanidine alkaloid with an unprecedented skeleton system
      derived from a polyketide precursor, (omega-3)-hydroxy fatty acid, and containing
      a 2-aminoethyl- and 3-aminopropyl-substituted morpholine hemiketal ring, has been
      isolated from the sponge Monanhora pulchra. The structure of 1 was assigned on
      the basis of detailed analysis of 1D and 2D NMR spectra, mass spectrometry, and
      results of chemical transformations. Compound 1 shows pro-apoptotic and cytoxic
      activities.

PMID- 20804152
TI  - Positions 94-98 of the lactose repressor N-subdomain monomer-monomer interface
      are critical for allosteric communication.
AB  - The central region of the LacI N-subdomain monomer-monomer interface includes
      residues K84, V94, V95, V96, S97, and M98. The side chains of these residues line
      the beta-strands at this interface and interact to create a network of
      hydrophobic, charged, and polar interactions that significantly rearranges in
      different functional states of LacI. Prior work showed that converting K84 to an
      apolar residue or converting V96 to an acidic residue impedes the allosteric
      response to inducer. Thus, we postulated that a disproportionate number of
      substitutions in this region of the monomer-monomer interface would alter the
      complex features of the LacI allosteric response. To explore this hypothesis,
      acidic, basic, polar, and apolar mutations were introduced at positions 94-98.
      Despite their varied locations along the beta-strands that flank the interface,
      ~70% of the mutations impact allosteric behavior, with the most significant
      effects found for charged substitutions. Of note, many of the LacI variants with
      minor functional impact exhibited altered stability to urea denaturation. The
      results confirm the critical role of amino acids 94-98 and indicate that this N
      subdomain interface forms a primary pathway in LacI allosteric response.

PMID- 20804153
TI  - Annexin A5-functionalized bimodal nanoparticles for MRI and fluorescence imaging
      of atherosclerotic plaques.
AB  - Apoptosis and macrophage burden are believed to correlate with atherosclerotic
      plaque vulnerability and are therefore considered important diagnostic and
      therapeutic targets for atherosclerosis. These cell types are characterized by
      the exposure of phosphatidylserine (PS) at their surface. In the present study,
      we developed and applied a small micellar fluorescent annexin A5-functionalized
      nanoparticle for noninvasive magnetic resonance imaging (MRI) of PS exposing
      cells in atherosclerotic lesions. Annexin A5-mediated target-specificity was
      confirmed with ellipsometry and in vitro binding to apoptotic Jurkat cells. In
      vivo T(1)-weighted MRI of the abdominal aorta in atherosclerotic ApoE(-/-) mice
      revealed enhanced uptake of the annexin A5-micelles as compared to control
      micelles, which was corroborated with ex vivo near-infrared fluorescence images
      of excised whole aortas. Confocal laser scanning microscopy (CLSM) demonstrated
      that the targeted agent was associated with macrophages and apoptotic cells,
      whereas the nonspecific control agent showed no clear uptake by such cells. In
      conclusion, the annexin A5-conjugated bimodal micelles displayed potential for
      noninvasive assessment of cell types that are considered to significantly
      contribute to plaque instability and therefore may be of great value in the
      assessment of atherosclerotic lesion phenotype.

PMID- 20804154
TI  - alpha-Lactalbumin forms with oleic acid a high molecular weight complex
      displaying cytotoxic activity.
AB  - alpha-Lactalbumin (LA) forms with oleic acid (OA) a complex which has been
      reported to induce the selective death of tumor cells. However, the mechanism by
      which this complex kills a wide range of tumor cell lines is as yet largely
      unknown. The difficulty in rationalizing the cytotoxic effects of the LA/OA
      complex can be due to the fact that the molecular aspects of the interaction
      between the protein and the fatty acid are still poorly understood, in particular
      regarding the oligomeric state of the protein and the actual molar ratio of OA
      over protein in the complex. Here, the effect of LA addition to an OA aqueous
      solution has been examined by dynamic light scattering measurements and
      transmission electron microscopy. Upon protein addition, the aggregation state of
      the rather insoluble OA is dramatically changed, and more water-soluble and
      smaller aggregates of the fatty acid are formed. A mixture of LA and an excess of
      OA forms a high molecular weight complex that can be isolated by size-exclusion
      chromatography and that displays cellular toxicity toward Jurkat cells. On the
      basis of gel filtration data, cross-linking experiments with glutaraldehyde, and
      OA titration, we evaluated that the isolated LA/OA complex is given by 4-5
      protein molecules that bind 68-85 OA molecules. The protein in the complex adopts
      a molten globule-like conformation, and it interacts with the fatty acid mostly
      through its alpha-helical domain, as indicated by circular dichroism measurements
      and limited proteolysis experiments. Overall, we interpret our and previous data
      as indicating that the cellular toxicity of a LA/OA complex is due to the effect
      of a protein moiety in significantly enhancing the water solubility of the
      cytotoxic OA and, therefore, that the protein/OA complex can serve mainly as a
      carrier of the toxic fatty acid in a physiological milieu.

PMID- 20804155
TI  - Tuning size and sensing properties in colloidal gold nanostars.
AB  - Gold nanostars are multibranched nanoparticles with sharp tips, which display
      extremely interesting plasmonic properties but require optimization. We present a
      systematic investigation of the influence of different parameters on the size,
      morphology, and monodispersity of Au nanostars obtained via seeded growth in
      concentrated solutions of poly(vinylpyrrolidone) in N,N-dimethylformamide.
      Controlled prereduction of Au(3+) to Au(+) was found to influence monodispersity
      (narrower plasmon bands), while the [HAuCl(4)]/[seed] molar ratio significantly
      affects the morphology and tip plasmon resonance frequency. We also varied the
      size of the seeds (2-30 nm) and found a clear influence on the final nanostar
      dimensions as well as on the number of spikes, while synthesis temperature
      notably affects the morphology of the particles, with more rounded morphologies
      formed above 60  degrees C. This rounding effect allowed us to confirm the
      importance of sharp tips on the optical enhancing behavior of these nanoparticles
      in surface-enhanced raman scattering (SERS). Additionally, the sensitivity toward
      changes in the local refractive index was found to increase for larger nanostars,
      though lower figure of merit (FOM) values were obtained because of the larger
      polydispersity.

PMID- 20804156
TI  - Mechanism for the light-induced O(2) evolution from H(2)O promoted by Ru(II) PNN
      complex: A DFT study.
AB  - The density functional theory (DFT) method was used to explore the light-induced
      O(2) formation from H(2)O promoted by Ru(II) PNN complex in the present work. The
      elimination of H(2)O(2) was found to be highly endothermic, which is not in
      competition with the H(2)O elimination and hydrogen transfer. The calculated
      results reported here do not support the mechanism proposed in a recent
      experiment, where H(2)O(2) was suggested as an important intermediate for
      formation of O(2). We proposed a new mechanism for formation of the triplet O(2)
      molecule, which contains the two steps of the concerted hydrogen transfer and
      dehydration. The light-induced O(2) evolution from water promoted by the Ru(II)
      complex was found to be a nonadiabatic process. The O-O bond is formed along the
      T(1) pathway as a result of the efficient S(1) -> T(1) intersystem crossing. All
      experimental findings on the light-induced O(2) evolution can be explained by the
      mechanism proposed in the present work.

PMID- 20804157
TI  - Setting anchor in the minor groove: in silico investigation into formamido N
      methylpyrrole and N-methylimidazole polyamides bound by cognate DNA sequences.
AB  - Tricyclic N-methylpyrrole (Py) and N-methylimidazole (Im) containing polyamide
      monocations are known to bind as stacked dimers within the minor groove of DNA,
      and those with N-terminal formamido (f) substituents bind in a staggered
      configuration with high specificity over a range of affinities. Although binding
      constants have been reported, there is not a clear understanding of why such
      constants vary significantly for polyamide dimers and their respective cognate
      DNA sequences. By employing computational tools, the following homodimer
      complexes have been addressed in this study: f-PyPyIm in complex with 5'
      d(GAACTAGTTC)-3', f-ImPyPy in complex with 5'-d(GAATGCATTC)-3', and f-ImPyIm in
      complex with 5'-d(GAACGCGTTC)-3'. These complexes were selected based on their 10
      to 100-fold differences in binding constants. From this study, it was possible
      to determine how polyamides anchor themselves within the minor groove of specific
      DNA sequences. This is done through several interactions that provide stability
      for specific recognition: (i) Py groups secure themselves between DNA base pairs,
      (ii) lone-pair-Pi interactions are formed between DNA deoxyribose O4' and Im
      groups nearest f, (iii) minor groove bases hydrogen bond to Im groups and amides
      of the polyamide backbone, (iv) f substituents rotate without leaving the minor
      groove of DNA and with this rotation form specific hydrogen bonds with electron
      rich sites on the floor of the minor groove, and (v) flexible charged N,N
      dimethylaminoalkyl substituents reside favorably in the minor groove of DNA.
      Results displayed the greatest amount of interactions and stability for dimer f
      ImPyIm in complex with 5'-d(GAACGCGTTC)-3' and the least amount in dimer f-PyPyIm
      in complex with 5'-d(GAACTAGTTC)-3'. Hence, for cognate DNA sequences, the
      relative binding strength of compounds was determined as f-ImPyIm > f-ImPyPy > f
      PyPyIm. This force-field-based computational study is in agreement with
      experimental results and provides a molecular rational for the binding constant
      values.

PMID- 20804158
TI  - Effective forces in square well and square shoulder fluids.
AB  - We derive an analytical expression for the effective force between a pair of
      macrospheres immersed in a sea of microspheres, in the case where the interaction
      between the two unlike species is assumed to be a square well or a square
      shoulder of given range and depth (or height). This formula extends a similar one
      developed in the case of hard core interactions only. Qualitative features of
      such effective force and the resulting phase diagrams are then analyzed in the
      limit of no interaction between the small particles. Approximate force profiles
      are then obtained by means of integral equation theories (PY and HNC) combined
      with the superposition approximation and compared with exact ones from direct
      Monte Carlo simulations.

PMID- 20804159
TI  - pharmACOphore: multiple flexible ligand alignment based on ant colony
      optimization.
AB  - The flexible superimposition of biologically active ligands is a crucial step in
      ligand-based drug design. Here we present pharmACOphore, a new approach for
      pairwise as well as multiple flexible alignment of ligands based on ant colony
      optimization (ACO; Dorigo, M.; Stutzle, T. Ant Colony Optimization; MIT Press:
      Cambridge, MA, USA, 2004). An empirical scoring function is used, which describes
      ligand similarity by minimizing the distance of pharmacophoric features. The
      scoring function was parametrized on pairwise alignments of ligand sets for four
      proteins from diverse protein families (cyclooxygenase-2, cyclin-dependent kinase
      2, factor Xa and peroxisome proliferator-activated receptor gamma). The derived
      parameters were assessed with respect to pose prediction performance on the
      independent FlexS data set ( Lemmen, C.; Lengauer, T.; Klebe, G. J. Med. Chem.
      1998, 41, 4502 - 4520) in exhausting pairwise alignments. Additionally, multiple
      flexible alignment experiments were carried out for the pharmacologically
      relevant targets trypsin and poly (ADP-ribose) polymerase (PARP). The results
      obtained show that the new procedure provides a robust and efficient way for the
      pairwise as well as multiple flexible alignment of small molecules.

PMID- 20804160
TI  - Superionic phase transition in KHSO4: a temperature-dependent Raman
      investigation.
AB  - Temperature-dependent Raman spectroscopic studies have been carried out on KHSO4
      single crystals in the temperature range 298-493 K. A structural phase transition
      driven by the lattice and molecular disorder is observed at 473 K. The spectral
      data enable an understanding of the nature of the lattice disorder across the
      phase transition leading to the superionic phase. The disorder in the HSO4-
      polymeric hydrogen-bonded chain leading to a higher symmetry in the high
      temperature phase is clearly captured from our Raman results. The internal S-OH
      and S-O stretching modes and, to a limited extent, the external modes throw light
      on the disorder mechanism and the enhancement of conductivity after transition.

PMID- 20804161
TI  - Thermoinduced lipid oxidation of a culinary oil: a kinetic study of the oxidation
      products by magnetic resonance spectroscopies.
AB  - (1)H NMR and EPR spectroscopies were employed to detect the evolution of lipid
      peroxidation products resulting from thermal stress in a vegetable oil. The
      obtained concentration profiles indicate that the secondary oxidation products
      (saturated and unsaturated aldehydes) may form not only via a direct degradation
      of primary oxidation products (hydroperoxides), as assumed in the classic kinetic
      models. In order to explain the observed concentration profiles, an alternate
      kinetic model is proposed where the aldehydes are additionally generated from
      hydroperoxides through an independent pathway.

PMID- 20804162
TI  - Field effect regulation of DNA translocation through a nanopore.
AB  - Field effect regulation of DNA nanoparticle translocation through a nanopore
      using a gate electrode is investigated using a continuum model, composed of the
      coupled Poisson-Nernst-Planck equations for the ionic mass transport and the
      Navier-Stokes equations for the hydrodynamic field. The field effect regulation
      of the DNA translocation relies on the induced electroosmotic flow (EOF) and the
      particle-nanopore electrostatic interaction. When the electrical double layers
      (EDLs) formed adjacent to the DNA nanoparticle and the nanopore wall are
      overlapped, the particle-nanopore electrostatic interaction could dominate over
      the EOF effect, which enables the DNA trapping inside the nanopore when the
      applied electric field is relatively low. However, the particle-nanopore
      electrostatic interaction becomes negligible if the EDLs are not overlapped. When
      the applied electric field is relatively high, a negative gate potential can slow
      down the DNA translocation by an order of magnitude, compared to a floating gate
      electrode. The field effect control offers a more flexible and electrically
      compatible approach to regulate the DNA translocation through a nanopore for DNA
      sequencing.

PMID- 20804164
TI  - G-quadruplex-modulated fluorescence detection of potassium in the presence of a
      3500-fold excess of sodium ions.
AB  - A label-free detection of K(+) was developed using G-quadruplex DNA (c-Myc)
      modulated fluorescence enhancement of tetrakis-(diisopropylguanidino) zinc
      phthalocyanine (Zn-DIGP). Upon the addition of increasing concentrations of
      potassium, a detection limit of 0.8 MUM for K(+) was easily achieved. Comparative
      titrations using sodium, lithium, ammonium, transition metal, or alkali earth
      salts revealed that the fluorescence enhancement was highly specific for
      potassium ions. This system has, for the first time, provided a means for
      detecting 40 MUM of K(+) even in the presence of a 3500-fold excess of Na(+)
      ions.

PMID- 20804163
TI  - Enzymatic processing of fumiquinazoline F: a tandem oxidative-acylation strategy
      for the generation of multicyclic scaffolds in fungal indole alkaloid
      biosynthesis.
AB  - Aspergillus fumigatus Af293 is a known producer of quinazoline natural products,
      including the antitumor fumiquinazolines, of which the simplest member is
      fumiquinazoline F (FQF) with a 6-6-6 tricyclic core derived from anthranilic
      acid, tryptophan, and alanine. FQF is the proposed biological precursor to
      fumiquinazoline A (FQA) in which the pendant indole side chain has been modified
      via oxidative coupling of an additional molecule of alanine, yielding a fused 6-5
      5 imidazoindolone. We recently identified fungal anthranilate-activating
      nonribosomal peptide synthetase (NRPS) domains through bioinformatics approaches.
      One domain previously identified is part of the trimodular NRPS Af12080, which we
      predict is responsible for FQF formation. We now show that two adjacent A.
      fumigatus ORFs, a monomodular NRPS Af12050 and a flavoprotein Af12060, are
      necessary and sufficient to convert FQF to FQA. Af12060 oxidizes the 2',3'-double
      bond of the indole side chain of FQF, and the three-domain NRPS Af12050 activates
      l-Ala as the adenylate, installs it as the pantetheinyl thioester on its carrier
      protein domain, and acylates the oxidized indole for subsequent intramolecular
      cyclization to create the 6-5-5 imidazolindolone of FQA. This work provides
      experimental validation of the fumiquinazoline biosynthetic cluster of A.
      fumigatus Af293 and describes an oxidative annulation biosynthetic strategy
      likely shared among several classes of polycyclic fungal alkaloids.

PMID- 20804165
TI  - Antiproliferative compounds from Pongamiopsis pervilleana from the Madagascar Dry
      Forest.
AB  - Bioassay-guided fractionation of an ethanol extract of the roots of the endemic
      Malagasy plant Pongamiopsis pervilleana led to the isolation of the three new
      compounds (2'R)-4'-hydroxyemoroidocarpan (1), pongavilleanine (3), and
      epipervilline (4) together with two known compounds, identified as emoroidocarpan
      (2) and rotenolone (5). The structures of all compounds were determined by
      physical, chemical, and spectroscopic evidence. The stereochemistry at C-2' of
      the previously reported compound emoroidocarpan was determined to be R by the
      observation of a negative Cotton effect at 474 nm in the CD spectrum of its
      osmate ester derivative. Compounds 2-5 displayed moderate antiproliferative
      activity against the A2780 human ovarian cancer cell line, and rotenolone also
      showed micromolar antiproliferative activity toward the breast cancer BT-549,
      prostate cancer DU 145, NSCLC NCI-H460, and colon cancer HCC-2998 cell lines.

PMID- 20804166
TI  - Mid-infrared spectroscopy coupled with chemometrics: a tool for the analysis of
      intact food systems and the exploration of their molecular structure-quality
      relationships - a review.

PMID- 20804167
TI  - Measuring cell wall thickness in living yeast cells using single molecular
      rulers.
AB  - Traditionally, the structural details of microbial cell walls are studied by thin
      section electron microscopy, a technique that is very demanding and requires
      vacuum conditions, thus precluding live cell experiments. Here, we present a
      method integrating single-molecule atomic force microscopy (AFM) and protein
      design to measure cell wall thickness in a living yeast cell. The basic idea
      relies on the expression of His-tagged membrane sensors of increasing lengths in
      yeast and their subsequent specific detection at the cell surface using a
      modified AFM tip. After establishing the method on a wild-type strain, we
      demonstrate its potential by measuring changes in cell wall thickness within a
      few nanometers range, which result from (bio)chemical treatments or from
      mutations affecting the cell wall structure. The single molecular ruler method
      presented here not only avoids cell fixation artifacts but also provides new
      opportunities for studying the dynamics of microbial cell walls during growth,
      drug action, or enzymatic modification.

PMID- 20804168
TI  - Hydration of amino acids from ultrasonic measurements.
AB  - In this paper the results of compressibility of aqueous solutions of amino acids
      in water and in aqueous HCl and NaOH solutions at 25  degrees C are presented.
      The effect of the charged protonated amino groups and deprotonated carboxylic
      groups on the hydration number was tested. The idea of additivity of the
      hydration number with the constituents of the solute molecule was successfully
      applied and discussed.

PMID- 20804169
TI  - Rhenium-catalyzed diastereoselective synthesis of aminoindanes via the insertion
      of allenes into a C-H bond.
AB  - Aminoindane derivatives were synthesized diastereoselectively by the treatment of
      aromatic imines with allenes in the presence of a catalytic amount of a rhenium
      complex, [HRe(CO)(4)](n). The allenes inserted into the aromatic C-H bonds.

PMID- 20804170
TI  - Photoacoustic spectrometer with a calculable cell constant for measurements of
      gases and aerosols.
AB  - We benchmark the performance of a photoacoustic spectrometer with a calculable
      cell constant in applications related to climate change measurements. As
      presently implemented, this spectrometer has a detection limit of 3.1 * 10(-9) W
      cm(-1) Hz(-1/2) for absorption by a gas and 1.5 * 10(-8) W cm(-1) Hz(-1/2) for
      soot particles. Nonstatistical uncertainty limited the accuracy of the instrument
      to ~1%, and measurements of the concentration of CO(2) in laboratory air agreed
      with measurements made using a cavity ring-down spectrometer, to within 1%.
      Measurements of the enhanced absorption resulting from ultrathin (<5 nm),
      nonabsorbing coatings on nanoscale soot particles demonstrate the sensitivity of
      this instrument. Together, these measurements show the instrument's ability to
      quantitatively measure the absorption coefficient for species of interest to the
      climate and atmospheric science communities. Because the system constant is
      known, in most applications the acoustic response of this instrument need not be
      calibrated against a sample of known optical density, a decided advantage in
      field applications. Routine enhancements, such as improved processing of the
      photoacoustic signal and higher laser beam power, should further increase the
      instrument's precision and sensitivity.

PMID- 20804171
TI  - In situ X-ray scattering studies of protein solution droplets drying on micro-
      and nanopatterned superhydrophobic PMMA surfaces.
AB  - Superhydrophobic poly(methyl methacrylate) surfaces with contact angles of ~170
      degrees  and high optical and X-ray transparencies have been fabricated through
      the use of optical lithography and plasma etching. The surfaces contain either a
      microscale pattern of micropillars or a random nanofibrillar pattern. Nanoscale
      asperities on top of the micropillars closely resemble Nelumbo nucifera lotus
      leaves. The evolution of the contact angle of water and lysozyme solution
      droplets during evaporation was studied on the micro- and nanopatterned surfaces,
      showing in particular contact-line pinning for the protein solution droplet on
      the nanopatterned surface. The microstructural evolution of lysozyme solution
      droplets was studied on both types of surfaces in situ under nearly contact-free
      conditions by synchrotron radiation microbeam wide-angle and small-angle X-ray
      scattering revealing the increasing protein concentration and the onset of
      precipitation. The solid residuals show hollow sphere morphologies.
      Rastermicrodiffraction of the detached residuals suggests about a 1/3 volume
      fraction of >=17 nm lysozyme nanocrystalline domains and about a 2/3 short-range
      order volume fraction. About 5-fold larger nanocrystalline domains were observed
      at the attachment points of the sphere to the substrates, which is attributed to
      particle growth in a shear flow. Such surfaces represent nearly contact-free
      sample supports for studies of inorganic and organic solution droplets, which
      find applications in biochips.

PMID- 20804172
TI  - Synthesis of highly fluorinated 2,2'-biphenols and 2,2'-bisanisoles.
AB  - Multiply fluorine-substituted iodo anisoles are efficiently coupled in an Ullmann
      type reaction to provide the corresponding bisanisoles. The coupling is selective
      and even tolerates bromo moieties. Subsequent deprotection of hydroxy groups
      gives access to highly fluorinated biphenols.

PMID- 20804173
TI  - High molecular weight polyglycerol-based multivalent mannose conjugates.
AB  - We report the synthesis and characterization of multivalent mannose conjugates
      based on high molecular weight hyperbranched polyglycerols (HPG). A range of
      glycoconjugates were synthesized from high molecular weight HPGs (up to 493 kDa)
      and varying mannose units (22-303 per HPG). Hemagglutination assays using fresh
      human red blood cells and concanavalin A (Con A) showed that HPG-mannose
      conjugates exhibited a large enhancement in the relative potency of conjugates
      (as high as 40000) along with a significant increment in relative activity per
      sugar (up to 255). The size of the HPG scaffold and the number of mannose
      residues per HPG were all shown to influence the enhancement of binding
      interactions with Con A. Isothermal titration calorimetry (ITC) experiments
      confirmed the enhanced binding affinity and showed that both molecular size and
      ligand density play important roles. The enhancement in Con A binding to the high
      molecular weight HPG-mannose conjugates is due to a combination of inter- and
      intramolecular mannose binding. A few fold increments in the binding constant
      were obtained over mannose upon covalent attachment to HPG. The binding
      enhancement is due to the highly favorable entropic contribution to the multiple
      interactions of Con A to mannose residues on HPG. The high molecular weight HPG
      mannose conjugates showed positive cooperativity in binding to Con A. Although
      carbohydrate density has less of an effect on functional valency of the conjugate
      compared to the molecular size, it determines the binding affinity.

PMID- 20804174
TI  - Binucleine 2, an isoform-specific inhibitor of Drosophila Aurora B kinase,
      provides insights into the mechanism of cytokinesis.
AB  - Aurora kinases are key regulators of cell division and important targets for
      cancer therapy. We report that Binucleine 2 is a highly isoform-specific
      inhibitor of Drosophila Aurora B kinase, and we identify a single residue within
      the kinase active site that confers specificity for Aurora B. Using Binucleine 2,
      we show that Aurora B kinase activity is not required during contractile ring
      ingression, providing insight into the mechanism of cytokinesis.

PMID- 20804176
TI  - STAT3 silencing in dendritic cells by siRNA polyplexes encapsulated in PLGA
      nanoparticles for the modulation of anticancer immune response.
AB  - In dendritic cells (DCs), the induction of signal transducer and activator of
      transcription 3 (STAT3) by tumor-derived factors (TDFs) renders DCs tolerogenic
      and suppresses their antitumor activity. Therefore, silencing STAT3 in DCs is
      beneficial for cancer immunotherapy. We have shown that STAT3 knockdown in B16
      murine melanoma by siRNA polyplexes of polyethylenimine (PEI) or its stearic acid
      derivative (PEI-StA) induces B16 cell death in vitro and in vivo. Here, we
      investigated the physical encapsulation of siRNA/PEI and PEI-StA polyplexes in
      poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) for STAT3 knockdown
      in DCs. PLGA NPs containing siRNA polyplexes of PEI (PLGA-P) and PEI-StA (PLGA
      PS) had an average diameter of ~350 to 390 nm and a zeta potential of ~-13 to -19
      mV, respectively. The encapsulation efficiency (E.E.) of siRNA in PLGA-P and PLGA
      PS was 26% and 43%, respectively. In both NP types, siRNA release followed a
      triphasic pattern, but it was faster in PLGA-PS. Our uptake study by fluorescence
      microscopy confirmed DC uptake and endosomal localization of both NP types. After
      exposure to B16.F10 conditioned medium, DCs showed high STAT3 and low CD86
      expression indicating impaired function. STAT3 silencing by PLGA-P and PLGA-PS of
      STAT3 siRNA restored DC maturation and functionality as evidenced by the
      upregulation of CD86 expression, high secretion of TNF-alpha and significant
      allogenic T cell proliferation. Moreover, encapsulation in PLGA NPs significantly
      reduced PEI-associated toxicity on DCs. We propose this formulation as a strategy
      for targeted siRNA delivery to DCs. The potential of this approach is not limited
      to STAT3 downregulation in DCs but can be used to target the expression of other
      proteins as well. Moreover, it can be combined with other means for cancer
      immunotherapy like cancer vaccine strategies.

PMID- 20804177
TI  - Simple shape-controlled synthesis of carbon hollow structures.
AB  - This study reports a simple method for the controlled synthesis of uniformly
      shaped carbon hollow structures by an ethanol-assisted thermolysis of zinc
      acetate. The experimental evidence reveals that the generated zinc oxide
      nanostructures act as in-situ templates to form the carbon hollow structures. The
      morphologies, including the shell thickness, cavity size, and aspect ratio, can
      be controlled by the reaction time and the heating procedure, and hollow
      nanospheres, nanocapsules, nanorods, and microtubes can be obtained. Experimental
      results show that the as-synthesized carbon hollow structures exhibit excellent
      thermal and structural stability to temperatures as high as 1200  degrees C.

PMID- 20804178
TI  - Synthesis and optical resolution of inherently chiral difunctionalized
      tribenzotriquinacenes.
AB  - The synthesis of several inherently chiral tribenzotriquinacenes (TBTQs) bearing
      one single mono- or difunctionalized aromatic nucleus and the optical resolution
      of one of these derivatives, a TBTQ-based salicylic acid (11), are described for
      the first time. Efficient access to enantiopure, inherently chiral
      tribenzotriquinacenes may lay a foundation for studies of novel container
      compounds, supramolecular aggregation, chiral recognition, and asymmetric
      catalysis.

PMID- 20804175
TI  - Lipid-protein correlations in nanoscale phospholipid bilayers determined by solid
      state nuclear magnetic resonance.
AB  - Nanodiscs are examples of discoidal nanoscale lipid-protein particles that have
      been extremely useful for the biochemical and biophysical characterization of
      membrane proteins. They are discoidal lipid bilayer fragments encircled and
      stabilized by two amphipathic helical proteins named membrane scaffolding protein
      (MSP), ~10 nm in size. Nanodiscs are homogeneous, easily prepared with
      reproducible success, amenable to preparations with a variety of lipids, and
      stable over a range of temperatures. Here we present solid-state nuclear magnetic
      resonance (SSNMR) studies on lyophilized, rehydrated POPC Nanodiscs prepared with
      uniformly (13)C-, (15)N-labeled MSP1D1 (Delta1-11 truncated MSP). Under these
      conditions, by SSNMR we directly determine the gel-to-liquid crystal lipid phase
      transition to be at 3 +/- 2  degrees C. Above this phase transition, the lipid
      (1)H signals have slow transverse relaxation, enabling filtering experiments as
      previously demonstrated for lipid vesicles. We incorporate this approach into two
      and three-dimensional heteronuclear SSNMR experiments to examine the MSP1D1
      residues interfacing with the lipid bilayer. These (1)H-(13)C and (1)H-(13)C
      (13)C correlation spectra are used to identify and quantify the number of lipid
      correlated and solvent-exposed residues by amino acid type, which furthermore is
      compared with molecular dynamics studies of MSP1D1 in Nanodiscs. This study
      demonstrates the utility of SSNMR experiments with Nanodiscs for examining lipid
      protein interfaces and has important applications for future structural studies
      of membrane proteins in physiologically relevant formulations.

PMID- 20804179
TI  - Effects of diazepam on gene expression and link to physiological effects in
      different life stages in zebrafish Danio rerio.
AB  - We applied zebrafish whole genome microarrays to identify molecular effects of
      diazepam, a neuropharmaceutical encountered in wastewater-contaminated
      environments, and to elucidate its neurotoxic mode of action. Behavioral studies
      were performed to analyze for correlations between altered gene expression with
      effects on the organism level. Male zebrafish and zebrafish eleuthero-embryos
      were exposed for 14 d or up to 3 d after hatching, respectively, to nominal
      levels of 273 ng/L and 273 MUg/L (determined water concentrations in the adult
      experiment 235 ng/L and 291 MUg/L). Among the 51 and 103 altered transcripts at
      both concentrations, respectively, the expression of genes involved in the
      circadian rhythm in adult zebrafish and eleuthero-embryos were of particular
      significance, as revealed both by microarrays and quantitative PCR. The swimming
      behavior of eleuthero-embryos was significantly altered at 273 MUg/L. The study
      leads to the conclusion that diazepam-induced alterations of genes involved in
      circadian rhythm are paralleled by effects in neurobehavior at high, but not at
      low diazepam concentrations that may occur in polluted environments.

PMID- 20804180
TI  - A rapid three-component MgI(2)-mediated synthesis of 3,3-pyrollidinyl
      spirooxindoles.
AB  - The rapid synthesis of 3,3-pyrollidinyl-spirooxindole cores from readily
      available cyclopropyl spirooxindoles and commercially available aldehydes,
      amines, and sulfonamides is reported. This general procedure utilizes microwave
      heating to access a biologically privileged scaffold in an efficient route
      amenable to library population.

PMID- 20804181
TI  - An accurate prediction of hydration free energies by combination of molecular
      integral equations theory with structural descriptors.
AB  - In this work, we report a novel method for the estimation of the hydration free
      energy of organic molecules, the structural descriptors correction (SDC) model.
      The method is based on a combination of the reference interaction site model
      (RISM) with several empirical corrections. The model requires only a small number
      of chemical descriptors associated with the main features of the chemical
      structure of solutes: excluded volume, branch, double bond, benzene ring,
      hydroxyl group, halogen atom, aldehyde group, ketone group, ether group, and
      phenol fragment. The optimum model was selected after testing of different RISM
      free energy expressions on a training set of 65 molecules. We show that the
      correction parameters of the SDC model are transferable between different
      chemical classes, which allows one to cover a wide range of organic solutes. The
      new model substantially increases the accuracy of calculated HFEs by RISM giving
      the standard deviation of the error for a test set of 120 organic molecules
      around 1.2 kcal/mol.

PMID- 20804182
TI  - Supramolecular interactions playing an integral role in the near-infrared Raman
      "excitonic" enhancement observed in beta-hematin (malaria pigment) and other
      related heme derivatives.
AB  - To gain more understanding into the mechanism that enables the dramatic resonant
      Raman enhancement of totally symmetric modes observed in hemozoin (malaria
      pigment) and other related heme supramolecular arrays when applying near-infrared
      excitation wavelengths, the iron(III) porphyrins Fe(TPP)Cl, [Fe(TPP)](2)O,
      Fe(OEP)Cl, and [Fe(OEP)](2)O along with beta-hematin (synthetic hemozoin or
      malaria pigment) were analyzed in the solid state using resonance Raman
      spectroscopy. The critical finding was that from the model compounds
      investigated, all except [Fe(OEP)](2)O exhibited the enhancement of the totally
      symmetric mode nu(4) when exciting the molecules with 782 and 830 nm laser lines.
      Through a detailed comparison of X-ray crystallographic structures, it is
      proposed that intermolecular noncovalent interactions play an integral role in
      enabling excitonic interactions to occur in these heme supramolecular systems.
      Comparison of the solid- and solution-phase electronic spectra in the near-IR
      region indicated more absorbance in the solid state between 800 and 900 nm. The
      electronic spectrum of [Fe(OEP)](2)O shows minimal absorbance in this region
      compared to that of the other compounds. All heme derivatives investigated have
      similar structure with a five-coordinate high-spin iron(III) ion. The
      crystallographic data indicate no significant differences in porphyrin geometry
      between TPP and OEP derivatives studied. However, [Fe(OEP)](2)O contains less
      supramolecular interactions in comparison to the other species. The
      supramolecular bonding enhances the probability of through-space interactions
      between the transition dipoles from electronic transitions of extended pi
      systems. Our results indicate that the intensity of nu(4) is in part strongly
      affected by C-H...X hydrogen bonding interactions when X is an electron-donating
      entity. Such information may have important implications in the design and
      monitoring of antimalarial drugs that specifically interfere with hemozoin
      formation.

PMID- 20804183
TI  - Dissolution study of metatorbernite: thermodynamic properties and the effect of
      pH and phosphate.
AB  - The uranyl copper-phosphate, metatorbernite, has been identified in the shallow
      vadose zone of the 300 A area at the Hanford site, WA, USA. Consequently,
      modeling the evolution of U concentrations in vadose zone porewaters driven by
      meteoric water recharge requires accurate knowledge of metatorbernite solubility.
      Previous determinations of the solubility constant for metatorbernite were under
      constrained. In the present contribution, the dissolution of natural
      metatorbernite crystals was studied at target pH 2.5 and 3.0, using both nitric
      and phosphoric acid. Steady state was approached from under- and supersaturation.
      The experiments and calculations yielded a preferred log K(sp) = -28.0 +/- 0.1
      that is significantly different than previously determined values. Further, both
      stoichiometric and nonstoichiometric dissolution was observed as a function of pH
      and aqueous phosphate concentration.

PMID- 20804184
TI  - Three-dimensional structure and growth of myelins.
AB  - After contact with water, surfactant lamellar phases (L(alpha)) can show
      spectacular interface instabilities: multibilayer tubules, so-called myelins,
      grow from the L(alpha)/water interface into the water. We have studied the shape,
      size, and growth of myelins in aqueous solutions of the nonionic surfactant
      C(12)E(3) (triethylene glycol monododecyl ether) during dissolution. We used a
      combination of different imaging techniques: optical microscopy providing 2-D
      projections of the sample and confocal microscopy offering a complete 3-D
      reconstruction. These techniques provide quantitative information on the shape
      and growth of myelins, such as their width, length, and depth profile as a
      function of time. The growth rate of myelins, characterized by a swelling or
      diffusion coefficient, was found to increase with surfactant mass fraction and,
      seemingly, with sample thickness. We demonstrate that myelin creaming due to
      buoyancy can explain the apparent dependence on sample thickness. Our experiments
      furthermore suggest that myelin growth is controlled by an interplay between the
      water mobility in the lamellar phase and the osmotic pressure difference between
      the lamellar phase and the contacting water.

PMID- 20804185
TI  - Nitrous oxide emissions from a large, impounded river: the Ohio River.
AB  - Models suggest that microbial activity in streams and rivers is a globally
      significant source of anthropogenic nitrous oxide (N(2)O), a potent greenhouse
      gas, and the leading cause of stratospheric ozone destruction. However, model
      estimates of N(2)O emissions are poorly constrained due to a lack of direct
      measurements of microbial N(2)O production and consequent emissions, particularly
      from large rivers. We report the first N(2)O budget for a large, nitrogen
      enriched river, based on direct measurements of N(2)O emissions from the water
      surface and N(2)O production in the sediments and water column. Maximum N(2)O
      emissions occurred downstream from Cincinnati, Ohio, a major urban center on the
      river, due to direct inputs of N(2)O from wastewater treatment plant effluent and
      higher rates of in situ production. Microbial activity in the water column and
      sediments was a source of N(2)O, and water column production rates were nearly
      double those of the sediments. Emissions exhibited strong seasonality with the
      highest rates observed during the summer and lowest during the winter. Our
      results indicate N(2)O dynamics in large temperate rivers may be characterized by
      strong seasonal cycles and production in the pelagic zone.

PMID- 20804186
TI  - Palladium-catalyzed carbonylative Heck-type reactions of alkyl iodides.
AB  - A palladium-catalyzed carbonylative Heck-type cyclization of alkyl halides is
      described. Treatment of a range of primary and secondary alkyl iodides with
      catalytic palladium(0) under CO pressure forms a variety of synthetically
      versatile enone products. The reactivity described represents a rare example of a
      palladium-catalyzed Heck-type cyclization involving unactivated alkyl halides
      with beta-hydrogens. Alkene substitution is well tolerated, and mono- and
      bicyclic carbocycles may be easily accessed.

PMID- 20804187
TI  - Ab initio study of water interaction with a Cu surface.
AB  - We have performed a first principles investigation of water interaction with a Cu
      surface. The calculated surface energy of a Cu(100) slab is in reasonable
      agreement with experimental data. The energy of water dissociation is in
      agreement with experiment. The results of the ab initio calculations are compared
      to experimental data on hydrogen partial pressure. It is concluded that
      Cu(OH)(ads) is formed due to a reaction between Cu and anoxic water. The energy
      of the Cu(100) slab with OH and H adsorbed is lower than the energy of the same
      slab with an adsorbed water molecule.

PMID- 20804188
TI  - Resolving the Au-adatom-alkanethiolate bonding site on Au(111) with domain
      boundary imaging using high-resolution scanning tunneling microscopy.
AB  - The bonding sites for Au-adatom-octanethiolate within the (?3*?3)R30 degrees 
      structure on Au(111) have been investigated with high-resolution scanning
      tunneling microscopy (STM) imaging. By establishing the relationship between the
      lateral positions of adsorbates on the top layer of gold and those inside an etch
      pit, we are able to determine the adsorption configuration with a high degree of
      accuracy for the elusive (?3*?3)R30 degrees  molecular layer. The boundary
      between adjacent SAM domains is also imaged with molecular resolution that allows
      the assignment of adsorption site in each domain without ambiguity. The standard
      (?3*?3)R30 degrees  alkanethiol SAM on Au(111) is found to consist of domains
      with Au-adatom-octanethiolate occupying the fcc hollows site, alongside domains
      where the hcp hollow site is occupied.

PMID- 20804189
TI  - Dilution technique to determine the hydrodynamic volume fraction of a vesicle
      suspension.
AB  - A simple dilution method to determine the hydrodynamic volume fraction of vesicle
      suspensions is presented. The vesicle suspension is diluted with a solution
      containing a tracer Y, which is similar to a component X already present in the
      suspending fluid and which does not bind to or permeate through the vesicles. The
      concentrations of X and Y in the suspending fluid measured after dilution are
      used to determine the volume fraction. Using this technique, the volume fractions
      of vesicle suspensions comprising cationic vesicles prepared in solutions of
      CaCl(2) (X) were measured by dilution with MgCl(2) (Y) solutions. Various
      experimental parameters such as the concentration of the MgCl(2) diluents and the
      dilution volume ratio were studied and their effects optimized to arrive at a
      robust recipe for measuring the volume fraction. It is demonstrated that the
      technique can be applied to concentrated suspensions containing multilamellar and
      polydisperse vesicles.

PMID- 20804190
TI  - Molecular structure of the dioctadecyldimethylammonium bromide (DODAB) bilayer.
AB  - Dioctadecyldimethylammonium bromide (DODAB) is a double-chained quaternary
      ammonium surfactant that assembles in water into bilayer structures. This letter
      reports the molecular dynamics (MD) computer simulations of the DODAB bilayer at
      25  degrees C. The simulations show that the surfactant membrane arranges
      spontaneously into the rippled phase (P(beta)(')) at that temperature. The
      ordering within the chain fragment closest to the hydrophilic head (carbon atoms
      1-5) is relatively low. It grows significantly for the carbon atoms located in
      the center of the membrane (atoms 6-17). The C6-C17 chain fragments are well
      aligned and tilted by ca. 15 degrees  with respect to the bilayer normal.

PMID- 20804191
TI  - Charge-transfer energy in the water-hydrogen molecular aggregate revealed by
      molecular-beam scattering experiments, charge displacement analysis, and ab
      initio calculations.
AB  - Integral cross-section measurements for the system water-H(2) in molecular-beam
      scattering experiments are reported. Their analysis demonstrates that the average
      attractive component of the water-H(2) intermolecular potential in the well
      region is about 30% stronger than dispersion and induction forces would imply. An
      extensive and detailed theoretical analysis of the electron charge displacement
      accompanying the interaction, over several crucial sections of the potential
      energy surface (PES), shows that water-H(2) interaction is accompanied by charge
      transfer (CT) and that the observed stabilization energy correlates
      quantitatively with CT magnitude at all distances. Based on the experimentally
      determined potential and the calculated CT, a general theoretical model is
      devised which reproduces very accurately PES sections obtained at the CCSD(T)
      level with large basis sets. The energy stabilization associated with CT is
      calculated to be 2.5 eV per electron transferred. Thus, CT is shown to be a
      significant, strongly stereospecific component of the interaction, with water
      functioning as electron donor or acceptor in different orientations. The general
      relevance of these findings for water's chemistry is discussed.

PMID- 20804192
TI  - Micropore analysis of polymer networks by gas sorption and 129Xe NMR
      spectroscopy: toward a better understanding of intrinsic microporosity.
AB  - The microporosity of two microporous polymer networks is investigated in detail.
      Both networks are based on a central spirobifluorene motif but have different
      linker groups, namely, imide and thiophene units. The microporosity of the
      networks is based on the "polymers of intrinsic microporosity (PIM)" design
      strategy. Nitrogen, argon, and carbon dioxide were used as sorbates in order to
      analyze the microporosity in greater detail. The gas sorption data was analyzed
      with respect to important parameters such as specific surface area, pore volume,
      and pore size (distribution). It is shown that the results can be strongly model
      dependent and swelling effects have to be regarded. (129)Xe NMR was used as an
      independent technique for the estimation of the average pore size of the polymer
      networks. The results indicate that both networks are mainly ultramicroporous
      (pore sizes < 0.8 nm) in the dry state, which was not expected based on the
      molecular design. Phase separation and network defects might influence the
      overall network morphology strongly. Finally, the observed swelling indicates
      that this "soft" microporous matter might have a different micropore size in the
      solvent swollen/filled state that in the dry state.

PMID- 20804193
TI  - Photoelectron imaging and density-functional investigation of bismuth and lead
      anions solvated in ammonia clusters.
AB  - We present the results of photoelectron velocity-map imaging experiments for the
      photodetachment of small negatively charged ammonia solvated Bi(n) and Pb(n) (n =
      1, 2) clusters at 527 nm. The vertical detachment energies of the observed
      multiple electronic bands and their respective anisotropy parameters for the
      solvated Bi and Pb anions and clusters derived from the photoelectron images are
      reported. The electronic bands of Bi(NH(3))(n=1,2) are distinct from the Bi metal
      ion in exhibiting a perpendicular distribution whereas the electronic bands in
      Pb(NH(3))(n=1,2), unlike the Pb anion, show an isotropic distribution with
      respect to the laser polarization. Density-functional theory calculations with a
      generalized gradient approximation for the exchange-correlation potential were
      performed on these clusters to determine their atomic and electronic structures.
      Calculated geometries show a dramatic change between anionic and neutral ammonia
      solvated Bi and Pb species. Anionic clusters exhibit van der Waals interactions
      between the hydrogen atoms of ammonia and the metal core, where it was determined
      that the negative charge is localized. Neutral clusters, on the other hand,
      present a covalent bond between the nitrogen atom of ammonia and the metal core.
      Calculated binding energies show an enhancement in the bonding of the (NH(3))(2)
      dimer in the presence of the anionic Bi(1,2)(-) and Pb(1,2)(-) metal ions. This
      is rationalized by the electrostatic interaction between the negative charged
      metal core and the hydrogen atoms of the ammonia molecule.

PMID- 20804194
TI  - Common threads in breast cancer proteomes.

PMID- 20804195
TI  - One-dimensional coordination polymers: complexity and diversity in structures,
      properties, and applications.

PMID- 20804196
TI  - Discovery of novel 5-benzylidenerhodanine and 5-benzylidenethiazolidine-2,4-dione
      inhibitors of MurD ligase.
AB  - We have designed, synthesized, and evaluated 5-benzylidenerhodanine- and 5
      benzylidenethiazolidine-2,4-dione-based compounds as inhibitors of bacterial
      enzyme MurD with E. coli IC(50) in the range 45-206 MUM. The high-resolution
      crystal structure of MurD in complex with (R,Z)-2-(3-[{4-([2,4-dioxothiazolidin-5
      ylidene]methyl)phenylamino}methyl)benzamido)pentanedioic acid [(R)-32] revealed
      details of the binding mode of the inhibitor within the active site and provides
      a good foundation for structure-based design of a novel generation of MurD
      inhibitors.

PMID- 20804197
TI  - Synthesis, anti-inflammatory activity, and in vitro antitumor effect of a novel
      class of cyclooxygenase inhibitors: 4-(aryloyl)phenyl methyl sulfones.
AB  - Following our previous research on anti-inflammatory drugs (NSAIDs), we report on
      the design and synthesis of 4-(aryloyl)phenyl methyl sulfones. These substances
      were characterized for their capacity to inhibit cyclooxygenase (COX-1 and COX-2)
      isoenzymes. Molecular modeling studies showed that the methylsulfone group of
      these compounds was inserted deep in the pocket of the human COX-2 binding site,
      in an orientation that precludes hydrogen bonding with Arg120, Ser353, and Tyr355
      through their oxygen atoms. The N-arylindole 33 was the most potent inhibitor of
      COX-2 and also the most selective (COX-1/COX-2 IC(50) ratio was 262). The indole
      derivative 33 was further tested in vivo for its anti-inflammatory activity in
      rats. This compound showed greater inhibitory activity than ibuprofen. Other
      compounds (20, 26, 9, and 30) showed strong activity against carrageenan-induced
      inflammation. The latter compounds showed a weak capacity to inhibit the
      proliferation of human cell lines K562, NCI-H460, and HT-29 in vitro.

PMID- 20804198
TI  - Discovery of 4-(5-(cyclopropylcarbamoyl)-2-methylphenylamino)-5-methyl-N
      propylpyrrolo[1,2-f][1,2,4]triazine-6-carboxamide (BMS-582949), a clinical
      p38alpha MAP kinase inhibitor for the treatment of inflammatory diseases.
AB  - The discovery and characterization of 7k (BMS-582949), a highly selective
      p38alpha MAP kinase inhibitor that is currently in phase II clinical trials for
      the treatment of rheumatoid arthritis, is described. A key to the discovery was
      the rational substitution of N-cyclopropyl for N-methoxy in 1a, a previously
      reported clinical candidate p38alpha inhibitor. Unlike alkyl and other
      cycloalkyls, the sp(2) character of the cyclopropyl group can confer improved H
      bonding characteristics to the directly substituted amide NH. Inhibitor 7k is
      slightly less active than 1a in the p38alpha enzymatic assay but displays a
      superior pharmacokinetic profile and, as such, was more effective in both the
      acute murine model of inflammation and pseudoestablished rat AA model. The
      binding mode of 7k with p38alpha was confirmed by X-ray crystallographic
      analysis.

PMID- 20804199
TI  - Inhalation by design: novel ultra-long-acting beta(2)-adrenoreceptor agonists for
      inhaled once-daily treatment of asthma and chronic obstructive pulmonary disease
      that utilize a sulfonamide agonist headgroup.
AB  - A novel series of potent and selective sulfonamide derived beta(2)-adrenoreceptor
      agonists are described that exhibit potential as inhaled ultra-long-acting
      bronchodilators for the treatment of asthma and chronic obstructive pulmonary
      disease. Analogues from this series mediate very long-lasting smooth muscle
      relaxation in guinea pig tracheal strips. The sulfonamide agonist headgroup
      confers high levels of intrinsic crystallinity that could relate to the acidic
      sulfonamide motif supporting a zwitterionic form in the solid state. Optimization
      of pharmacokinetic properties was achieved through targeted introduction of a
      phenolic moiety to support rapid phase II clearance, thereby minimizing systemic
      exposure following inhalation and reducing systemically mediated adverse events.
      Compound 38 (PF-610355) is identified as a clinical candidate from this series,
      with in vivo duration of action studies confirming its potential for once-daily
      use in humans. Compound 38 is currently in advanced phase II clinical studies.

PMID- 20804200
TI  - Mineralization, biodegradation, and drug release behavior of gelatin/apatite
      composite microspheres for bone regeneration.
AB  - Gelatin microspheres are well-known for their capacity to release growth factors
      in a controlled manner, but gelatin microspheres do not calcify in the absence of
      so-called bioactive substances that induce deposition of calcium phosphate (CaP)
      bone mineral. This study has investigated if CaP nanocrystals can be incorporated
      into gelatin microspheres to render these inert microspheres bioactive without
      compromising the drug releasing properties of gelatin microspheres. Incorporation
      of CaP nanocrystals into gelatin microspheres resulted into reduced
      biodegradation and drug release rates, whereas their calcifying capacity
      increased strongly compared to inert gelatin microspheres. The reduced drug
      release rate was correlated to the reduced degradation rate as caused by a
      physical cross-linking effect of CaP nanocrystals dispersed in the gelatin
      matrix. Consequently, these composite microspheres combine beneficial drug
      releasing properties of organic gelatin with the calcifying capacity of a
      dispersed CaP phase.

PMID- 20804201
TI  - Synthesis and characterization of amphiphilic lipopolymers for micellar drug
      delivery.
AB  - The objective of this study was to design lipopolymers for hydrophobic drug
      delivery. Poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene
      carbonate-graft-dodecanol) (PEG-PCD) lipopolymers were synthesized and
      characterized by (1)H NMR, FT-IR, GPC, and DSC. The critical micelle
      concentration (CMC) of PEG-PCD micelles was around 10(-8) M and decreased with
      increasing length of hydrophobic block. PEG-PCD micelles could efficiently load a
      model drug embelin into its hydrophobic core and significantly improve its
      solubility. The loading capacity was dependent on the polymer core structure, but
      the length of hydrophobic core had little effect. PEG-PCD formed both spherical
      and cylindrical micelles, which were dependent on the copolymer structure and
      composition. PEG-PCD lipopolymers with various hydrophobic core lengths showed
      similar drug release profiles, which were slower than that of poly(ethylene
      glycol)-block-poly(2-methyl-2-benzoxycarbonyl-propylene carbonate) (PEG-PBC)
      micelles. Embelin loaded PEG-PCD micelles showed significant inhibition of C4-2
      prostate cancer cell proliferation, while no obvious cellular toxicity was
      observed for blank micelles.

PMID- 20804203
TI  - 1H NMR relaxometry study of a rod-like chiral liquid crystal in its isotropic,
      cholesteric, TGBA*, and TGBC* phases.
AB  - The molecular dynamics of a chiral liquid crystal showing a rich variety of
      frustrated mesophases has been investigated by means of 1H NMR relaxometry. The
      interest in this lactate derivative, HZL 7/*, is related to a large range of
      thermal stabilities of the twist grain boundary (TGB) phases. Dispersions of the
      1H spin-lattice relaxation times, T1, in the frequency range from 300 MHz to 5
      kHz were measured and consistently analyzed in the isotropic, chiral nematic,
      TGBA*, and two TGBC* phases. In the isotropic and N* phases, a three-exponential
      magnetization decay was observed and assigned to three specific molecular groups
      of the HZL 7/* (molecular core, methyl, and methylene groups). In the TGB phases,
      all T1 components merge into a single one. The analysis of the T1 dispersion in
      the TGBA* phase shows that the translational self-diffusion relaxation mechanism
      dominates over a broad frequency range and that layer undulations are less
      relevant than the relaxation contribution associated with the diffusion process
      across the TGB structure. In the TGBC1* phase, the T1 dispersion presents a
      strong contribution of in-layer tilt direction fluctuations (T1(-1) proportional
      to nu(-1/2)), while, in the TGBC2* phase, the linear frequency dependence of T1
      could be associated with a much stronger contribution of layer undulations than
      for the other TGB phases. This is at present the first molecular dynamics
      investigation on several TGB phases by means of 1H NMR relaxometry.

PMID- 20804204
TI  - Discrepancies in thorium oxide solubility values: study of attachment/detachment
      processes at the solid/solution interface.
AB  - The solubility of thorium under oxide and/or hydroxide forms has been extensively
      studied for many years. Nevertheless, a large discrepancy in the solubility
      values is noticed in the literature. We study Th atom exchange between thorium
      oxide surfaces and various aqueous solutions (0.01 mol.L(-1) NaCl for 0.0 < pH <
      5.2) to address this issue. By solid-state characterization [X-ray photoelectron
      spectroscopy (XPS), scanning electron microscopy, and atomic force microscopy],
      we determined that 80% of the XPS accessible near the surface region of sintered
      thorium oxide is represented by the less reactive ThO(2)(cr) grains. The
      remaining 20% corresponds to ThO(x)(OH)(y)(H(2)O)(z), which is largely associated
      with grain boundaries. Only the latter fraction is involved in solid/solution
      exchange mechanisms. Local conditions (thorium concentrations, pH values, etc.)
      in grain boundaries lead to an adjustment of the "local solubility constraints"
      and explain the thorium concentration measured in our experiments. For pH <5.2,
      the thorium concentration and pH gradient between the bulk solution and grain
      boundary regions imply that the solubility values mainly depend on the
      availability and accessibility of ThO(x)(OH)(y)(H(2)O)(z). We have performed two
      solubility experiments with a (232)ThO(2)(cr) solid in a 0.01 mol.L(-1) NaCl
      solution for 300 days. In a first experiment, we measured (232)Th concentrations
      in dissolution experiments in order to determine the detachment rates of Th atoms
      from the solid surface. In a subsequent step, we added (229)Th to the solution in
      order to measure the surface attachment rate for dissolved Th atoms. This allowed
      an assessment of the net balance of Th atom exchange at the solid/solution
      interface. The empirical solubility data do not correspond to the thermodynamic
      bulk phase/solution equilibrium because measured solution concentrations are
      controlled by site-specific exchange mechanisms at the solid/solution interface.
      Therefore, for sparingly soluble solids, one needs to quantify site-specific
      surface attachment and detachment rates if one wants to assess solubility
      constraints.

PMID- 20804206
TI  - Leveraging nanoscale plasmonic modes to achieve reproducible enhancement of
      light.
AB  - The strongly enhanced and localized optical fields that occur within the gaps
      between metallic nanostructures can be leveraged for a wide range of
      functionality in nanophotonic and optical metamaterial applications. Here, we
      introduce a means of precise control over these nanoscale gaps through the
      application of a molecular spacer layer that is self-assembled onto a gold film,
      upon which gold nanoparticles (NPs) are deposited electrostatically. Simulations
      using a three-dimensional finite element model and measurements from single NPs
      confirm that the gaps formed by this process, between the NP and the gold film,
      are highly reproducible transducers of surface-enhanced resonant Raman
      scattering. With a spacer layer of roughly 1.6 nm, all NPs exhibit a strong Raman
      signal that decays rapidly as the spacer layer is increased.

PMID- 20804205
TI  - Cholesterol modulates the membrane effects and spatial organization of membrane
      penetrating ligands for G-protein coupled receptors.
AB  - The ligands of certain G-protein coupled receptors (GPCRs) are membrane soluble
      and reach their target from the lipid bilayer. Lipid composition and dynamics
      will therefore modulate the activity of these receptors, but specific roles of
      lipid components, including the ubiquitous cholesterol (Chol), are not clear. We
      have probed the organization and dynamics of such a lipid-bilayer-penetrating
      ligand, the endogenous ligand for the kappa-opioid receptor (KOR) dynorphin A (1
      17) (DynA), using molecular dynamics (MD) simulations of DynA in cholesterol
      depleted and cholesterol-enriched model membranes. DynA is found to penetrate
      deep inside fluid dimyristoylphosphatidylcholine (DMPC) bilayers, and resides
      with its N-terminal helix at ~6 A away from the bilayer midplane, in a tilted
      orientation, at an ~50 degrees  angle with respect to the membrane normal. In
      contrast, DynA inside DMPC/Chol membranes with 20% cholesterol (DMPC/Chol) is
      situated with its helical segment ~5 A higher, i.e., closer to the lipid/water
      interface and in a relatively vertical orientation. The DMPC membrane shows
      greater thinning around the insertion and permits a stronger influx of water
      inside the hydrocarbon core than the DMPC/Chol membranes. Relating these results
      to data about key GPCR residues that have been implicated in interactions with
      membrane-inserting GPCR ligands, we conclude that the position of DynA in
      DMPC/Chol, but not in pure DMPC, correlates with generally proposed GPCR ligand
      entry pathways. Our predictions provide a possible mechanistic explanation as to
      why DynA binding to KOR, and the subsequent activation of the receptor, is
      facilitated in cholesterol-enriched environments. A quantitative description of
      DynA-induced membrane deformations is obtained with a continuum theory of
      membrane deformations (CTMD) that is based on hydrophobic matching. Comparison
      with the MD data reveals the significance of the lipid tail packing energy
      contribution in the DMPC/Chol mixtures in predicting equilibrium membrane shape
      around DynA. On this basis, specific corrections are introduced to this energy
      term within the CTMD framework, thereby extending the applicability of the CTMD
      framework to lipid raft mixtures and their interactions with GPCR proteins and
      their ligands.

PMID- 20804202
TI  - Nitrile-containing pharmaceuticals: efficacious roles of the nitrile
      pharmacophore.

PMID- 20804207
TI  - Molecular seesaw: a three-way motion and motion-induced surface modification.
AB  - We introduce a three-way molecular motion which can be a suitable switching
      system in future molecule-based nanocircuits. A real-space investigation revealed
      that vinylferrocene adsorbs site-specifically on the Ge(100) surface and then
      shows a reversible tilting motion, similar to a seesaw. Unlike conventional
      molecular motions, it not only has three stable switching states at room
      temperature but also shows a motion-induced surface-structure modification,
      allowing surface-mediated signal transmission. Demonstrated STM-tip influence on
      the motion allows the feasibility of tip-induced manipulation.

PMID- 20804208
TI  - Nanostructured gold architectures formed through high pressure-driven sintering
      of spherical nanoparticle arrays.
AB  - We have demonstrated pressure-directed assembly for preparation of a new class of
      chemically and mechanically stable gold nanostructures through high pressure
      driven sintering of nanoparticle assemblies at room temperature. We show that
      under a hydrostatic pressure field, the unit cell dimension of a 3D ordered
      nanoparticle array can be reversibly manipulated allowing fine-tuning of the
      interparticle separation distance. In addition, 3D nanostructured gold
      architecture can be formed through high pressure-induced nanoparticle sintering.
      This work opens a new pathway for engineering and fabrication of different metal
      nanostructured architectures.

PMID- 20804209
TI  - Formation yields of glyoxal and methylglyoxal from the gas-phase OH radical
      initiated reactions of toluene, xylenes, and trimethylbenzenes as a function of
      NO2 concentration.
AB  - Aromatic hydrocarbons comprise 20% of non-methane volatile organic compounds in
      urban areas and are transformed mainly by atmospheric chemical reactions with OH
      radicals during daytime. In this work we have measured the formation yields of
      glyoxal and methylglyoxal from the OH radical-initiated reactions of toluene,
      xylenes, and trimethylbenzenes over the NO2 concentration range (0.2-10.3) * 1013
      molecules cm(-3). For toluene, o-, m-, and p-xylene, and 1,3,5-trimethylbenzene,
      the yields showed a dependence on NO2, decreasing with increasing NO2
      concentration and with no evidence for formation of glyoxal or methylglyoxal from
      the reactions of the OH-aromatic adducts with NO2. In contrast, for 1,2,3- and
      1,2,4-trimethylbenzene the glyoxal and methylglyoxal formation yields were
      independent of the NO2 concentration within the experimental uncertainties.
      Extrapolations of our results to NO2 concentrations representative of the ambient
      atmosphere results in the following glyoxal and methylglyoxal yields,
      respectively: for toluene, 26.0 +/- 2.2% and 21.5 +/- 2.9%; for o-xylene, 12.7 +/
      1.9% and 33.1 +/- 6.1%; for m-xylene, 11.4 +/- 0.7% and 51.5 +/- 8.5%; for p
      xylene, 38.9 +/- 4.7% and 18.7 +/- 2.2%; for 1,2,3-trimethylbenzene, 4.7 +/- 2.4%
      and 15.1 +/- 3.3%; for 1,2,4-trimethylbenzene, 8.7 +/- 1.6% and 27.2 +/- 8.1%;
      and for 1,3,5-trimethylbenzene, 58.1 +/- 5.3% (methylglyoxal).

PMID- 20804211
TI  - Efficient synthesis of pyrazolopyrimidine libraries.

PMID- 20804210
TI  - Nanometer to millimeter scale peptide-porphyrin materials.
AB  - AQ-Pal14 is a 30-residue polypeptide that was designed to form an alpha-helical
      coiled coil that contains a metal-binding 4-pyridylalanine residue on its solvent
      exposed surface. However, characterization of this peptide shows that it exists
      as a three-stranded coiled coil, not a two-stranded one as predicted from its
      design. Reaction with cobalt(III) protoporphyrin IX (Co-PPIX) produces a six
      coordinate Co-PPIX(AQ-Pal14)(2) species that creates two coiled-coil
      oligomerization domains coordinated to opposite faces of the porphyrin ring. It
      is found that this species undergoes a buffer-dependent self-assembly process:
      nanometer-scale globular materials were formed when these components were reacted
      in unbuffered H(2)O, while millimeter-scale, rod-like materials were prepared
      when the reaction was performed in phosphate buffer (20 mM, pH 7). It is
      suggested that assembly of the globular material is dictated by the
      conformational properties of the coiled-coil forming AQ-Pal14 peptide, whereas
      that of the rod-like material involves interactions between Co-PPIX and phosphate
      ion.

PMID- 20804212
TI  - Steady-state kinetic and inhibition studies of the mammalian target of rapamycin
      (mTOR) kinase domain and mTOR complexes.
AB  - The mammalian target of rapamycin (mTOR) is a Ser/Thr protein kinase and a major
      controller of cell growth. In cells, mTOR forms two distinct multiprotein
      complexes, mTORC1 and mTORC2. The mTORC1 complex can phosphorylate 4EBP1 and
      S6K1, two key regulators of translation initiation, whereas mTORC2 phosphorylates
      AKT1, an event required for AKT1 activation. Here, we expressed and purified
      human mTORC1 and mTORC2 from HEK-293 cells using FLAG-M2 affinity chromatography.
      Western blotting analysis using phospho-specific antibodies indicated that
      recombinant mTORC1 and mTORC2 exhibit distinct substrate preferences in vitro,
      consistent with their roles in cells. To improve our understanding of the
      enzymatic properties of mTOR alone and mTOR in its complex form, steady-state
      kinetic profiles of truncated mTOR containing the kinase domain (residues 1360
      2549) and mTORC1 were determined. The results revealed that mTORC1 is
      catalytically less active than truncated mTOR, as evidenced by 4.7- and 3.1-fold
      decreases in catalytic efficiency, k(cat)/K(m), for ATP and 4EBP1, respectively.
      We also found that truncated mTOR undergoes autophosphorylation through an
      intramolecular mechanism. Mass spectrometric analysis identified two novel mTOR
      autophosphorylation sites, Ser2454 and either Thr2473 or Thr2474, in addition to
      the previously reported Ser2481 site. Truncated mTOR and mTORC1 were completely
      inhibited by ATP competitive inhibitors PI103 and BEZ235 and partially inhibited
      by rapamycin/FKBP12 in a noncompetitive fashion toward ATP. All inhibitors tested
      exhibited similar inhibitory potencies between mTORC1 and truncated mTOR
      containing the kinase domain. Our studies presented here provide the first
      detailed kinetic studies of a recombinant mTOR complex.

PMID- 20804213
TI  - Quantum linear magnetoresistance in multilayer epitaxial graphene.
AB  - We report the first observation of linear magnetoresistance (LMR) in multilayer
      epitaxial graphene grown on SiC. We show that multilayer epitaxial graphene
      exhibits large LMR from 2.2 K up to room temperature and that it can be best
      explained by a purely quantum mechanical model. We attribute the observation of
      LMR to inhomogeneities in the epitaxially grown graphene film. The large
      magnitude of the LMR suggests potential for novel applications in areas such as
      high-density data storage and magnetic sensors and actuators.

PMID- 20804214
TI  - Influence of disorder on conductance in bilayer graphene under perpendicular
      electric field.
AB  - Electron transport in bilayer graphene placed under a perpendicular electric
      field is revealed experimentally. Steep increase of the resistance is observed
      under high electric field; however, the resistance does not diverge even at low
      temperatures. The observed temperature dependence of the conductance consists of
      two contributions: the thermally activated (TA) conduction and the variable range
      hopping (VRH) conduction. We find that for the measured electric field range (0
      1.3 V/nm) the mobility gap extracted from the TA behavior agrees well with the
      theoretical prediction for the band gap opening in bilayer graphene, although the
      VRH conduction deteriorates the insulating state more seriously in bilayer
      graphene with smaller mobility. These results show that the improvement of the
      mobility is crucial for the successful operation of the bilayer graphene field
      effect transistor.

PMID- 20804216
TI  - Controlled manipulation and in situ mechanical measurement of single co nanowire
      with a laser-induced cavitation bubble.
AB  - The flow induced by a single laser-induced cavitation bubble is used to
      manipulate individual Co nanowires. The short-lived (<20 MUs) bubble with a
      maximum size of 45 MUm is created in an aqueous solution with a laser pulse.
      Translation, rotation, and radial motion of the nanowire can be selectively
      achieved by varying the initial distance and orientation of the bubble with
      respect to the nanowire. Depending on the initial distance, the nanowire can be
      either pushed away or pulled toward the laser focus. No translation is observed
      for a distance further than approximately 60 MUm, while at closer distance, the
      nanowire can be bent as a result of the fast flow induced during the bubble
      collapse. Studying the dynamics of the shape recovery allows an estimation of the
      Young's modulus of the nanowire. The low measured Young's modulus (in a range
      from 9.6 to 13.0 GPa) of the Co nanowire is attributed to a softening effect due
      to structural defects and surface oxidation layer. Our study suggests that this
      bubble-based technique allows selectively transporting, orienting, and probing
      individual nanowires and may be exploited for constructing functional
      nanodevices.

PMID- 20804215
TI  - Autoassembly protein arrays for analyzing antibody cross-reactivity.
AB  - We report an autoassembly protein array capable of rapidly screening for aberrant
      antibody-antigen binding events. Our technique combines magnetic nanoparticle
      technology with proximity-based, magnetically responsive nanosensors for rapid
      (under 15 min) and high-density screening of antibody cross-reactivity at
      sensitivities down to 50 fM in a homogeneous assay. This method will enable the
      identification of the precise cause of aberrant or cross-reactive binding events
      in an easy-to-use, rapid, and high-throughput manner.

PMID- 20804217
TI  - Proteomic profile regulated by the anticancer peptide CIGB-300 in non-small cell
      lung cancer (NSCLC) cells.
AB  - CIGB-300 is a proapoptotic peptide-based drug that abrogates the CK2-mediated
      phosphorylation. This peptide has antineoplastic effect on lung cancer cells in
      vitro and in vivo. To understand the mechanisms involved on such anticancer
      activity, the NCI-H125 cell line proteomic profile after short-term incubation
      (45 min) with CIGB-300 was investigated. As determined by 2-DE or 2D-LC-MS/MS,
      137 proteins changed their abundances more than 2-fold in response to the CIGB
      300 treatment. The expression levels of proteins related to ribosome biogenesis,
      metastasis, cell survival and proliferation, apoptosis, and drug resistance were
      significantly modulated by the presence of CIGB-300. The protein translation
      process was the most affected (23% of the identified proteins). From the proteome
      analysis of the NCI-H125 cell line, novel potentialities for CIGB-300 as
      anticancer agent were evidenced.

PMID- 20804218
TI  - Selective chemical intervention in the proteome of Caenorhabditis elegans.
AB  - We present the first study of protein regulation by ligands in Caenorhabditis
      elegans. The ligands were peptidyl-prolyl isomerase inhibitors of cyclophilins.
      Up-regulation is observed for several heat shock proteins and one ligand in
      particular caused a greater than 2-fold enhancement of cyclophilin CYN-5.
      Additionally, several metabolic enzymes display elevated levels. This approach,
      using label-free relative quantification, provides an extremely attractive way of
      measuring the effect of ligands on an entire proteome, with minimal sample
      pretreatment, which could be applicable to large-scale studies. In this initial
      study, which compares the effect of three ligands, 54 unique proteins have been
      identified that are up- (51) or down- (3) regulated in the presence of a given
      ligand. A total of 431 C. elegans proteins were identified. Our methodology
      provides an intriguing new direction for in vivo screening of the effects of
      novel and untested ligands at the whole organism level.

PMID- 20804220
TI  - Mechanically robust, rapidly actuating, and biologically functionalized
      macroporous poly(N-isopropylacrylamide)/silk hybrid hydrogels.
AB  - A route toward mechanically robust, rapidly actuating, and biologically
      functionalized polymeric actuators using macroporous soft materials is described.
      The materials were prepared by combining silk protein and a synthetic polymer
      (poly(N-isopropylacrylamide) (PNIAPPm)) to form interpenetrating network
      materials and macroporous structures by freeze-drying, with hundreds of
      micrometer diameter pores and exploiting the features of both polymers related to
      dynamic materials and structures. The chemically cross-linked PNIPAAm networks
      provided stimuli-responsive features, while the silk interpenetrating network
      formed by inducing protein beta-sheet crystallinity in situ for physical cross
      links provided material robustness, improved expansion force, and enzymatic
      degradability. The macroporous hybrid hydrogels showed enhanced thermal
      responsive properties in comparison to pure PNIPAAm hydrogels, nonporous
      silk/PNIPAAm hybrid hydrogels, and previously reported macroporous PNIPAAm
      hydrogels. These new systems reach near equilibrium sizes in shrunken/swollen
      states in less than 1 min, with the structural features providing improved
      actuation rates and stable oscillatory properties due to the macroporous
      transport and the mechanically robust silk network. Confocal images of the
      hydrated hydrogels around the lower critical solution temperature (LCST) revealed
      macropores that could be used to track changes in the real time morphology upon
      thermal stimulus. The material system transformed from a macroporous to a
      nonporous structure upon enzymatic degradation. To extend the utility of the
      system, an affinity platform for a switchable or tunable system was developed by
      immobilizing biotin and avidin on the macropore surfaces.

PMID- 20804221
TI  - Cold acclimation proteome analysis reveals close link between the up-regulation
      of low-temperature associated proteins and vernalization fulfillment.
AB  - Low-temperature (LT) stress is one of the major limiting factors in cereal
      production in cold high-altitude mountainous areas of Iran where cereals are
      exposed to variable periods of temperatures in the vernalization range during the
      autumn season. Cereals regulate their development through adaptive mechanisms
      that are responsive to low but nonfreezing temperatures. We exploited a proteomic
      approach to determine the interrelationship between vernalization fulfillment and
      expression of low-temperature (LT)-induced protein in most hardy Norstar and semi
      hardy Azar2 wheat (Triticum aestivum L. em. Thell). These cultivars were
      subjected to 12 h of cold acclimating temperature (2  degrees C) over a period of
      0-89 days. LT tolerance, as measured by LT50, and vernalization fulfillment, as
      estimated from final leaf number (FLN), was determined at intervals throughout
      the acclimation period. A significant decrease in FLN associated with LT
      treatment indicated that Norstar and Azar2 had vernalization responses. Azar2
      achieved its vernalization fulfillment and maximum LT tolerance (~ -8  degrees C)
      by 28 days of acclimation. However, Norstar had a longer vernalization
      requirement (between 35 and 42 days) and reached vernalization fulfillment and
      maximum LT tolerance (~ -18.7  degrees C) about the same time as vernalization
      fulfillment. We applied a two-dimensional electrophoresis-based proteomics
      approach to analyze changes in the leaf proteome of two genotypes, Norstar and
      Azar2, during cold acclimation. Using MALDI-TOF/TOF mass spectrometry, 66 LT
      associated proteins could significantly be identified. These proteins were
      categorized into cold-regulated proteins, antifreezing proteins, oxidative stress
      defense, photosynthesis, chloroplast post-transcriptional regulation,
      metabolisms, and protein synthesis. A close association between the vernalization
      fulfillment and the start of a decline in the protein accumulation of hardy
      Norstar with a long vernalization requirement and semi-hardy Azar2 with a short
      vernalization requirement was observed. This finding supported the hypothesis
      that developmental trait which was regulated by vernalization had a regulatory
      influence over LT proteome response and highlight a close link between the up
      regulation of LT-associated proteins and vernalization fulfillment at the
      molecular level in wheat.

PMID- 20804222
TI  - Burden and cost of hospital admissions for vaccine-preventable paediatric
      pneumococcal disease and non-typable Haemophilus influenzae otitis media in New
      Zealand.
AB  - INTRODUCTION: Streptococcus pneumoniae (Sp.) is a leading cause of paediatric
      bacterial meningitis, pneumonia and acute otitis media, as is non-typable
      Haemophilus influenzae (NTHi) for acute otitis media. In 2008, a 7-valent
      conjugated pneumococcal vaccine (PCV7) was included in the New Zealand (NZ)
      childhood immunization schedule. OBJECTIVE: To estimate the potentially vaccine
      preventable annual hospital admissions and cost to the NZ Government of
      paediatric admissions for pneumococcal disease and NTHi otitis media prior to the
      immunization programme. METHODS: Admissions (2000-7) and deaths (2000-5) in
      children aged<20 years with pneumococcal meningitis or bacteraemia, pneumonia or
      otitis media were identified in national datasets and linked by unique patient
      identifiers. New episodes of illness were defined as admissions occurring >30
      days after discharge from a previous admission. Informed by the literature,
      pneumococcal pneumonia episodes were estimated at 33% of all-cause pneumonia
      admissions; Sp. and NTHi otitis media episodes were estimated jointly at 72% of
      otitis media admissions. Each episode was assigned a single diagnosis according
      to the following hierarchy: meningitis>bacteraemia>pneumonia>otitis media.
      Incidence rates for episodes were determined for 2000-7 (meningitis, bacteraemia
      and pneumonia) and 2006-7 (otitis media). Annual DRG-based costs for pneumococcal
      meningitis, bacteraemia, pneumonia and otitis media were estimated as (episode
      rate)x(DRG cost weight per episode)x(2007 population)x(national price per cost
      weight). RESULTS: Episode rates for pneumococcal meningitis, bacteraemia and
      pneumonia were stable in 2000-7, highest in the second 6 months of life and
      declined steeply over the first 5 years of life. Mean rates per 100000 in 2000-7
      were 18.4, 27.6 and 464 for pneumococcal meningitis, bacteraemia and pneumonia,
      respectively, for children aged<2 years; 8.4, 14.9 and 295 for children aged<5
      years (including those aged<2 years); and 2.2, 4.4 and 97 for children aged<20
      years (including those aged<5 years). Mean rates per 100000 in 2006-7 for Sp. and
      NTHi otitis media combined were 631 (surgical) and 197 (medical) for children
      aged<2 years; 691 and 116 for children aged<5 years; and 281 and 35 for children
      aged<20 years. Pacific Island and indigenous Maori children generally had higher
      rates than European/other children. Rates increased with socioeconomic
      disadvantage, across all diagnoses. The annual cost to Government of pneumococcal
      disease and NTHi otitis media admissions for children aged<20 years was estimated
      at New Zealand dollars ($NZ)9.95 million (range 7.7-12.2 million) [about $US7.1
      million]. Most of this cost was shared between pneumococcal pneumonia (48%) and
      otitis media (45%), and 78% was incurred in the first 2 years of life. Estimated
      annual paediatric mortality rates per 100 000 for children aged<5 years were
      0.48, 0.30 and 0.54 for pneumococcal meningitis, bacteraemia and pneumonia,
      respectively. The analysis predicted four or five pneumococcal deaths per year
      (range 1-8) for children aged<5 years. CONCLUSIONS: Prior to the introduction of
      a national Sp. immunization programme, hospital admissions for Sp. disease and
      NTHi otitis media in NZ cost about $NZ10 million annually, mostly for children
      aged<2 years and particularly for those living in relative socioeconomic
      deprivation and for Pacific Island and Maori children. There were about five
      pneumococcal deaths annually. With adjustment for local serotypes, vaccine
      serotype coverage and uptake, immunization with any of the three available
      pneumococcal vaccines would reduce this burden substantially.

PMID- 20804223
TI  - Global spending on orphan drugs in France, Germany, the UK, Italy and Spain
      during 2007.
AB  - BACKGROUND: Orphan drugs are indicated for the treatment of rare diseases which,
      in the EU, are defined as those with a prevalence of <5 per 10000 inhabitants.
      Characteristically, these diseases negatively affect health-related quality of
      life and may be life threatening. The EU has passed legislation to encourage
      pharmaceutical companies to invest in research programmes into rare diseases,
      with the aim of developing new, safe and effective orphan drugs. OBJECTIVES: To
      describe the status of orphan drugs in five countries in the EU (France, Germany,
      the UK, Italy and Spain), estimate the mean annual cost per patient and
      indication of these orphan drugs, and determine the associated cost of these
      drugs in comparison with overall spending on drugs in each country (year 2007
      values). METHODS: The analysis was limited solely to costs of orphan drugs with
      sales data available for 2007. The mean annual cost per patient was estimated
      using recommended regimens for maintenance dose and duration from the summary of
      product characteristics. Likewise, the ratio between annual costs per patient for
      treatment of each disease and its prevalence was calculated. Sales data were
      available for at least one of the countries studied for 38 of the 44 orphan drugs
      authorized by the European Medicines Agency. Only 21 products had data available
      for all five countries studied. RESULTS: Germany was the country with access to
      the largest number of orphan drugs (36), followed by the UK (34), Spain (28),
      France (27) and Italy (25). The mean annual cost per patient and indication of
      the 38 orphan drugs on the market ranged widely from ?331 to ?337,501. It appears
      that orphan drugs indicated to treat diseases with a prevalence of <2 per 10000
      inhabitants have higher annual per-patient costs than those indicated to treat
      diseases with a higher prevalence. The percentage of total drug spending
      accounted for by orphan drugs in 2007 was 1.7% in France, 2.1% in Germany, 1.0%
      in the UK, 1.5% in Italy and 2.0% in Spain, with an average overall percentage of
      1.7% for these five countries. CONCLUSIONS: In 2007, spending on orphan drugs in
      five European countries was acceptable in terms of the percentage of these
      countries' overall drug expenditure. Mean annual costs per patient of orphan
      drugs varied widely, with costs being related to the prevalence of the disease
      for which the product is indicated.

PMID- 20804224
TI  - Cost of illness and drivers of cost in atrial fibrillation in Sweden and Germany.
AB  - BACKGROUND: Atrial fibrillation (AF) is an important public health problem in
      European countries. AF is associated with increased morbidity and mortality, e.g.
      from heart failure and thromboembolic events. Little data have previously been
      presented regarding the costs of treatment in patients with AF. OBJECTIVE: To
      estimate total direct and indirect costs in patients with AF in Sweden and
      Germany, and to identify determinants of total costs. METHODS: A cross-sectional
      observational study was conducted through surveys to patients and their treating
      physician in primary care and in hospital outpatient cardiology departments in
      Sweden and Germany. A total of 922 patients with AF as diagnosed in clinical
      practice were enrolled and completed the study. Data were collected on medical
      history, treatment, medical and non-medical resource use, and employment status.
      Costs (year 2005 values) were calculated by multiplying resources used with
      prices specific for Sweden and Germany, respectively. RESULTS: Total annual costs
      per patient were ?7241 in Sweden and ?5586 in Germany. Slightly less than 70% of
      total costs were judged as being AF related in both countries. Costs of AF
      related medication were about 2% of total costs in both countries. In a
      generalized regression model, costs were found to increase with age, but were
      lower in patients aged>65 years than in those aged<or=65 years, due to the
      absence of indirect costs in older patients. Costs were highest in patients with
      persistent AF and lowest in those with permanent AF. Co-morbidities with a
      significant influence on costs included coronary heart disease, cerebrovascular
      disease, heart failure and asthma. CONCLUSIONS: Current costs in AF patients are
      driven by the consequences of AF, while costs for specific treatments for AF are
      low. The addition of new, effective and safe treatment options could potentially
      reduce overall healthcare costs in AF.

PMID- 20804225
TI  - Cost effectiveness of long-acting risperidone in Sweden.
AB  - BACKGROUND: In Sweden, risperidone long-acting injectable (RLAI) is generally
      used in a population of schizophrenia patients who are at a high risk of being
      non-compliant. However, RLAI might also be suitable for use in the general
      schizophrenia population. OBJECTIVES: To analyse the clinical and economic
      effects of RLAI in the Swedish treatment practice using a discrete-event
      simulation (DES) model. Treatment outcomes and direct costs were analysed for
      both the high-risk non-compliant patient population and the general schizophrenia
      population. METHODS: An existing DES model was adapted to simulate the treatment
      of schizophrenia in Sweden. Model inputs were based on literature research and
      supplemented with expert opinion. In the high-risk non-compliant schizophrenia
      population, RLAI was compared with haloperidol LAI. The analysis was built upon
      differences in symptom reduction, time between relapses, compliance and adverse
      effect profile between the two drugs. Main outcomes were the predicted
      incremental (discounted) costs (?) and effects (QALYs). In the general
      schizophrenia population, RLAI was compared with oral olanzapine. This analysis
      was built upon differences in compliance and adverse effects between the drugs.
      Multivariate probabilistic sensitivity analyses (PSA) were carried out to assess
      the sensitivity of the results of the two analyses. RESULTS: In the high-risk non
      compliant patient population, RLAI was predicted to generate 0.103 QALYs per
      patient over 3 years while realizing cost savings of ?5013 (year 2007 values)
      compared with haloperidol LAI. The main driver of the cost effectiveness of RLAI
      was the difference in Positive and Negative Syndrome Scale (PANSS) reduction
      between the two drugs, followed by the difference in adverse effects. The PSA
      showed that, in this setting, RLAI had a probability of 100% of being cost
      effective at a willingness-to-pay (WTP) threshold of ?43,300 per QALY gained,
      compared with haloperidol LAI. The probability that RLAI combines additional
      effectiveness with cost savings compared with haloperidol LAI was estimated at
      94%. When analysing RLAI in the general schizophrenia population, it was
      predicted to generate 0.043 QALYs and save ?239 per patient over 5 years compared
      with olanzapine. Compliance was the main driver of the cost effectiveness of RLAI
      in this scenario. In the PSA it was shown that RLAI had a probability of 78% of
      being cost effective at a WTP threshold of ?43,300 per QALY gained, compared with
      olanzapine. The estimated probability that RLAI combines additional effectiveness
      with cost savings was 50% and the probability that RLAI is less effective and
      more costly than olanzapine was negligible (0.2%). CONCLUSIONS: Treatment with
      RLAI is suggested to result in improved QALYs combined with cost savings compared
      with haloperidol LAI among the Swedish, high-risk non-compliant schizophrenia
      patient population. In the general schizophrenia population, RLAI also resulted
      in positive incremental QALYs and cost savings, when compared with olanzapine.
      However, the estimates used in the model for compliance and symptom reduction
      need further validation through naturalistic-based studies with reasonable follow
      up to more definitely establish the real-life differences between RLAI and the
      comparators in the considered patient populations and to further reduce the
      uncertainty of these parameters.

PMID- 20804226
TI  - Issues surrounding orphan disease and orphan drug policies in Europe.
AB  - An orphan disease is a disease with a very low prevalence. Although there are
      5000-7000 orphan diseases, only 50 orphan drugs (i.e. drugs developed to treat
      orphan diseases) were marketed in the EU by the end of 2008. In 2000, the EU
      implemented policies specifically designed to stimulate the development of orphan
      drugs. While decisions on orphan designation and the marketing authorization of
      orphan drugs are made at the EU level, decisions on drug reimbursement are made
      at the member state level. The specific features of orphan diseases and orphan
      drugs make them a high-priority issue for policy makers. The aim of this article
      is to identify and discuss several issues surrounding orphan disease and drug
      policies in Europe. The present system of orphan designation allows for drugs for
      non-orphan diseases to be designated as orphan drugs. The economic factors
      underlying orphan designation can be questioned in some cases, as a low
      prevalence of a certain indication does not equal a low return on investment for
      the drug across its indications. High-quality evidence about the clinical added
      value of orphan drugs is rarely available at the time of marketing authorization,
      due to the low number of patients. A balance must be struck between ethical and
      economic concerns. To this effect, there is a need to initiate a societal
      dialogue on this issue, to clarify what society wants and accepts in terms of
      ethical and economic consequences. The growing budgetary impact of orphan drugs
      puts pressure on drug expenditure. Indications can be extended for an orphan drug
      and the total prevalence across indications is not considered. Finally,
      cooperation needs to be fostered in the EU, particularly through a standardized
      approach to the creation and use of registries. These issues require further
      attention from researchers, policy makers, health professionals, patients,
      pharmaceutical companies and other stakeholders with a view to optimizing orphan
      disease and drug policies in Europe.

PMID- 20804227
TI  - Economic efficiency of alcohol policy.

PMID- 20804228
TI  - Clinical utility of cancer family history collection in primary care.
AB  - OBJECTIVES: This systematic review aimed to evaluate, within unselected
      populations: the (1) performance of family history (FHx)-based models in
      predicting cancer risk; (2) overall benefits and harms associated with
      established cancer prevention interventions; (3) impact of FHx-based risk
      information on the uptake of preventive interventions; and (4) potential for
      harms associated with collecting cancer FHx. DATA SOURCES: MEDLINE, EMBASE,
      CINAHL, Cochrane Central, Cochrane Database of Systematic Reviews, and PsycINFO
      were searched from 1990 to June 2008 inclusive. Cancer guidelines and
      recommendations were searched from 2002 forward and systematic reviews from 2003
      to June 2008. REVIEW METHODS: Standard systematic review methodology was
      employed. Eligibility criteria included English studies evaluating breast,
      colorectal, ovarian, or prostate cancers. Study designs were restricted to
      systematic review, experimental and diagnostic types. Populations were limited to
      those unselected for cancer risk. Interventions were limited to collection of
      cancer FHx; primary and/or secondary prevention interventions for breast,
      colorectal, ovarian, and prostate cancers. RESULTS: Accuracy of models. Seven
      eligible studies evaluated systems based on the Gail model, and on the Harvard
      Cancer Risk Index. No evaluations demonstrated more than modest discriminatory
      accuracy at an individual level. No evaluations were identified relevant to
      ovarian or prostate cancer risk. Efficacy of preventive interventions. From 29
      eligible systematic reviews, seven found no experimental studies evaluating
      interventions of interest. Of the remaining 22, none addressed ovarian cancer
      prevention. The reviews were generally based on limited numbers of randomized or
      controlled clinical trials. There was no evidence either to support or refute the
      use of selected chemoprevention interventions, there was some evidence of
      effectiveness for mammography and fecal occult blood testing. Uptake of
      intervention. Three studies evaluated the impact of FHx-based risk information on
      uptake of clinical preventive interventions for breast cancer. The evidence is
      insufficient to draw conclusions on the effect of FHx-based risk information on
      change in preventive behavior. Potential harms of FHx taking. One uncontrolled
      trial evaluated the impact of FHx-based breast cancer risk information on
      psychological outcomes and found no evidence of significant harm. CONCLUSIONS:
      Our review indicates a very limited evidence base with which to address all four
      of the research questions: 1) the few evaluations of cancer risk prediction
      models do not suggest useful individual predictive accuracy; 2) the experimental
      evidence base for primary and secondary cancer prevention is very limited; 3)
      there is insufficient evidence to assess the effect of FHx-based risk assessment
      on preventive behaviors; 4) there is insufficient evidence to assess whether FHx
      based personalized risk assessment directly causes adverse outcomes.

PMID- 20804229
TI  - Treatment of common hip fractures.
AB  - OBJECTIVES: To conduct a systematic review and synthesize the evidence for the
      effects of surgical treatments for subcapital and
      intertrochanteric/subtrochanteric hip fractures on patient-focused outcomes for
      elderly patients. DATA SOURCES: MEDLINE, Cochrane databases, Scirus, and
      ClinicalTrials.gov, and expert consultants. We also manually searched reference
      lists from relevant systematic reviews. REVIEW METHODS: High quality quasi
      experimental design studies were used to examine relationships between patient
      characteristics, type of fracture, and patient outcomes. Randomized controlled
      trials were used to examine relationships between type of surgical treatment and
      patient outcomes. Patient mortality was examined with Forest plots. Narrative
      analysis was used for pain, quality of life (QoL), and functional outcomes due to
      inconsistently measured and reported outcomes. RESULTS: Mortality does not appear
      to differ by device class, or by devices within a class. Nor, on the whole, do
      pain, functioning, and QoL. Some internal fixation devices may confer earlier
      return to functioning over others for some patients, but such gains are very
      short lived. Very limited results suggest that subcapital hip fracture patients
      with total hip replacements have improved patient outcomes over internal
      fixation, but it is unclear whether these results would continue to hold if the
      analyses included the full complement of relevant covariates. Age, gender,
      prefracture functioning, and cognitive impairment appear to be related to
      mortality and functional outcomes. Fracture type does not appear to be
      independently related to patient outcomes. Again, however, the observational
      literature does not include the full complement of potential covariates and it is
      uncertain if these results would hold. CONCLUSIONS: Several factors limit our
      ability to definitively answer the key questions posed in this study using the
      existing literature. Limited perspectives lead to incomplete sets of independent
      variables included in analyses. Specific populations are poorly defined and
      separated for comparative study. Fractures with widely varying biomechanical
      problems are often lumped together. Outcome variables are inconsistently measured
      and reported, making it very difficult to aggregate or even compare results. If
      future high quality trials continue to support the evidence that differences in
      devices are short term at best, within the first few weeks to few months of
      recovery, policy implications involve establishing the value of a shorter
      recovery relative to the cost of the new device. As the literature generally
      focuses on community dwelling elderly patients, more attention needs to be
      directed toward understanding implications of surgical treatment choices for the
      nursing home population.

PMID- 20804230
TI  - Outcomes of community health worker interventions.
AB  - OBJECTIVES: To conduct a systematic review of the evidence on characteristics of
      community health workers (CHWs) and CHW interventions, outcomes of such
      interventions, costs and cost-effectiveness of CHW interventions, and
      characteristics of CHW training. DATA SOURCES: We searched MEDLINE, Cochrane
      Collaboration resources, and the Cumulative Index to Nursing and Allied Health
      Literature for studies published in English from 1980 through November 2008.
      REVIEW METHODS: We used standard Evidence-based Practice Center methods of dual
      review of abstracts, full-text articles, abstractions, quality ratings, and
      strength of evidence grades. We resolved disagreements by consensus. RESULTS: We
      included 53 studies on characteristics and outcomes of CHW interventions, 6 on
      cost-effectiveness, and 9 on training. CHWs interacted with participants in a
      broad array of locations, using a spectrum of materials at varying levels of
      intensity. We classified 8 studies as low intensity, 18 as moderate intensity,
      and 27 as high intensity, based on the type and duration of interaction.
      Regarding outcomes, limited evidence (five studies) suggests that CHW
      interventions can improve participant knowledge when compared with alternative
      approaches such as no intervention, media, mail, or usual care plus pamphlets. We
      found mixed evidence for CHW effectiveness on participant behavior change (22
      studies) and health outcomes (27 studies): some studies suggested that CHW
      interventions can result in greater improvements in participant behavior and
      health outcomes when compared with various alternatives, but other studies
      suggested that CHW interventions provide no statistically different benefits than
      alternatives. Low or moderate strength of evidence suggests that CHWs can
      increase appropriate health care utilization for some interventions (30 studies).
      The literature showed mixed results of effectiveness when analyzed by clinical
      context: CHW interventions had the greatest effectiveness relative to
      alternatives for some disease prevention, asthma management, cervical cancer
      screening, and mammography screening outcomes. CHW interventions were not
      significantly different from alternatives for clinical breast examination, breast
      self-examination, colorectal cancer screening, chronic disease management, or
      most maternal and child health interventions. Six studies with economic and cost
      information yielded insufficient data to evaluate the cost-effectiveness of CHW
      interventions relative to other community health interventions. Limited evidence
      described characteristics of CHW training; no studies examined the impact of CHW
      training on health outcomes. CONCLUSIONS: CHWs can serve as a means of improving
      outcomes for underserved populations for some health conditions. The
      effectiveness of CHWs in numerous areas requires further research that addresses
      the methodological limitations of prior studies and that contributes to
      translating research into practice.

PMID- 20804231
TI  - Cooperating when "you" and "I" are treated fairly: the moderating role of leader
      prototypicality.
AB  - We developed a model predicting that leaders are most effective in stimulating
      follower cooperation when they consistently treat all group members in a fair
      manner and are prototypical (i.e., representative of the group's values and
      norms). In support of this idea, we consistently found that group members
      cooperated most when prototypical leaders treated themselves as well as their
      coworkers fairly across a laboratory experiment and 3 cross-sectional field
      studies. These findings highlight the important role of others' fairness
      experiences and perceptions in influencing one's own reactions and also the role
      of leaders as representing the group's values and norms. We discuss implications
      for fairness theory and the leader prototypicality literature.

PMID- 20804232
TI  - A formal, computational theory of multiple-goal pursuit: integrating goal-choice
      and goal-striving processes.
AB  - Understanding the processes involved when pursuing multiple goals over time is a
      central question for motivational theorists. A dynamic, computational model
      integrating theories of goal striving and goal choice is presented to account for
      data emerging from Schmidt and DeShon's (2007) multiple-goal-pursuit protocol.
      The simulated results match the results reported in their study, including the
      finding that relative discrepancy from the goals positively predicted resource
      allocation early on but negatively predicted it toward the end of the session.
      Variance in parameters in the model also accounted for individual differences
      found in the data. Discussion focuses on the theoretical contribution of formally
      integrating elements of self-regulation theories, further empirical work needed
      to test the model, and further theoretical work needed to continue the
      integration process exemplified here.

PMID- 20804233
TI  - Surviving the Holocaust: a meta-analysis of the long-term sequelae of a genocide.
AB  - The current set of meta-analyses elucidates the long-term psychiatric,
      psychosocial, and physical consequences of the Holocaust for survivors. In 71
      samples with 12,746 participants Holocaust survivors were compared with their
      counterparts (with no Holocaust background) on physical health, psychological
      well-being, posttraumatic stress symptoms, psychopathological symptomatology,
      cognitive functioning, and stress-related physiology. Holocaust survivors were
      less well adjusted, as apparent from studies on nonselected samples (trimmed
      combined effect size d = 0.22, 95% CI [0.13, 0.31], N = 9,803) and from studies
      on selected samples (d = 0.45, 95% CI [0.32, 0.59], N = 2,943). In particular,
      they showed substantially more posttraumatic stress symptoms (nonselect studies:
      d = 0.72, 95% CI [0.46, 0.98], N = 1,763). They did not lag, however, much behind
      their comparisons in several other domains of functioning (i.e., physical health,
      stress-related physical measures, and cognitive functioning) and showed
      remarkable resilience. The coexistence of stress-related symptoms and good
      adaptation in some other areas of functioning may be explained by the unique
      characteristics of the symptoms of Holocaust survivors, who combine resilience
      with the use of defensive mechanisms. In most domains of functioning no
      differences were found between Israeli samples and samples from other countries.
      The exception was psychological well-being: For this domain it was found that
      living in Israel rather than elsewhere can serve as a protective factor. A
      biopsychological stress-diathesis model is used to interpret the findings, and
      future directions for research and social policy are discussed.

PMID- 20804234
TI  - A theoretical and empirical review of the death-thought accessibility concept in
      terror management research.
AB  - Terror management theory (TMT) highlights the motivational impact of thoughts of
      death in various aspects of everyday life. Since its inception in 1986, research
      on TMT has undergone a slight but significant shift from an almost exclusive
      focus on the manipulation of thoughts of death to a marked increase in studies
      that measure the accessibility of death-related cognition. Indeed, the number of
      death-thought accessibility (DTA) studies in the published literature has grown
      substantially in recent years. In light of this increasing reliance on the DTA
      concept, the present article is meant to provide a comprehensive theoretical and
      empirical review of the literature employing this concept. After discussing the
      roots of DTA, the authors outline the theoretical refinements to TMT that have
      accompanied significant research findings associated with the DTA concept. Four
      distinct categories (mortality salience, death association, anxiety-buffer
      threat, and dispositional) are derived to organize the reviewed DTA studies, and
      the theoretical implications of each category are discussed. Finally, a number of
      lingering empirical and theoretical issues in the DTA literature are discussed
      with the aim of stimulating and focusing future research on DTA specifically and
      TMT in general.

PMID- 20804235
TI  - The efficacy of violence prediction: a meta-analytic comparison of nine risk
      assessment tools.
AB  - Actuarial risk assessment tools are used extensively to predict future violence,
      but previous studies comparing their predictive accuracies have produced
      inconsistent findings as a result of various methodological issues. We conducted
      meta-analyses of the effect sizes of 9 commonly used risk assessment tools and
      their subscales to compare their predictive efficacies for violence. The effect
      sizes were extracted from 28 original reports published between 1999 and 2008,
      which assessed the predictive accuracy of more than one tool. We used a within
      subject design to improve statistical power and multilevel regression models to
      disentangle random effects of variation between studies and tools and to adjust
      for study features. All 9 tools and their subscales predicted violence at about
      the same moderate level of predictive efficacy with the exception of Psychopathy
      Checklist--Revised (PCL-R) Factor 1, which predicted violence only at chance
      level among men. Approximately 25% of the total variance was due to differences
      between tools, whereas approximately 85% of heterogeneity between studies was
      explained by methodological features (age, length of follow-up, different types
      of violent outcome, sex, and sex-related interactions). Sex-differentiated
      efficacy was found for a small number of the tools. If the intention is only to
      predict future violence, then the 9 tools are essentially interchangeable; the
      selection of which tool to use in practice should depend on what other functions
      the tool can perform rather than on its efficacy in predicting violence. The
      moderate level of predictive accuracy of these tools suggests that they should
      not be used solely for some criminal justice decision making that requires a very
      high level of accuracy such as preventive detention.

PMID- 20804236
TI  - Linking "big" personality traits to anxiety, depressive, and substance use
      disorders: a meta-analysis.
AB  - We performed a quantitative review of associations between the higher order
      personality traits in the Big Three and Big Five models (i.e., neuroticism,
      extraversion, disinhibition, conscientiousness, agreeableness, and openness) and
      specific depressive, anxiety, and substance use disorders (SUD) in adults. This
      approach resulted in 66 meta-analyses. The review included 175 studies published
      from 1980 to 2007, which yielded 851 effect sizes. For a given analysis, the
      number of studies ranged from three to 63 (total sample size ranged from 1,076 to
      75,229). All diagnostic groups were high on neuroticism (mean Cohen's d = 1.65)
      and low on conscientiousness (mean d = -1.01). Many disorders also showed low
      extraversion, with the largest effect sizes for dysthymic disorder (d = -1.47)
      and social phobia (d = -1.31). Disinhibition was linked to only a few conditions,
      including SUD (d = 0.72). Finally, agreeableness and openness were largely
      unrelated to the analyzed diagnoses. Two conditions showed particularly distinct
      profiles: SUD, which was less related to neuroticism but more elevated on
      disinhibition and disagreeableness, and specific phobia, which displayed weaker
      links to all traits. Moderator analyses indicated that epidemiologic samples
      produced smaller effects than patient samples and that Eysenck's inventories
      showed weaker associations than NEO scales. In sum, we found that common mental
      disorders are strongly linked to personality and have similar trait profiles.
      Neuroticism was the strongest correlate across the board, but several other
      traits showed substantial effects independent of neuroticism. Greater attention
      to these constructs can significantly benefit psychopathology research and
      clinical practice.

PMID- 20804237
TI  - A review of EEG, ERP, and neuroimaging studies of creativity and insight.
AB  - Creativity is a cornerstone of what makes us human, yet the neural mechanisms
      underlying creative thinking are poorly understood. A recent surge of interest
      into the neural underpinnings of creative behavior has produced a banquet of data
      that is tantalizing but, considered as a whole, deeply self-contradictory. We
      review the emerging literature and take stock of several long-standing theories
      and widely held beliefs about creativity. A total of 72 experiments, reported in
      63 articles, make up the core of the review. They broadly fall into 3 categories:
      divergent thinking, artistic creativity, and insight. Electroencephalographic
      studies of divergent thinking yield highly variegated results. Neuroimaging
      studies of this paradigm also indicate no reliable changes above and beyond
      diffuse prefrontal activation. These findings call into question the usefulness
      of the divergent thinking construct in the search for the neural basis of
      creativity. A similarly inconclusive picture emerges for studies of artistic
      performance, except that this paradigm also often yields activation of motor and
      temporoparietal regions. Neuroelectric and imaging studies of insight are more
      consistent, reflecting changes in anterior cingulate cortex and prefrontal areas.
      Taken together, creative thinking does not appear to critically depend on any
      single mental process or brain region, and it is not especially associated with
      right brains, defocused attention, low arousal, or alpha synchronization, as
      sometimes hypothesized. To make creativity tractable in the brain, it must be
      further subdivided into different types that can be meaningfully associated with
      specific neurocognitive processes.

PMID- 20804238
TI  - Control and interference in task switching--a review.
AB  - The task-switching paradigm offers enormous possibilities to study cognitive
      control as well as task interference. The current review provides an overview of
      recent research on both topics. First, we review different experimental
      approaches to task switching, such as comparing mixed-task blocks with single
      task blocks, predictable task-switching and task-cuing paradigms, intermittent
      instructions, and voluntary task selection. In the 2nd part, we discuss findings
      on preparatory control mechanisms in task switching and theoretical accounts of
      task preparation. We consider preparation processes in two-stage models, consider
      preparation as an all-or-none process, address the question of whether
      preparation is switch-specific, reflect on preparation as interaction of cue
      encoding and memory retrieval, and discuss the impact of verbal mediation on
      preparation. In the 3rd part, we turn to interference phenomena in task
      switching. We consider proactive interference of tasks and inhibition of recently
      performed tasks indicated by asymmetrical switch costs and n-2 task-repetition
      costs. We discuss stimulus-based interference as a result of stimulus-based
      response activation and stimulus-based task activation, and response-based
      interference because of applying bivalent rather than univalent responses,
      response repetition effects, and carryover of response selection and execution.
      In the 4th and final part, we mention possible future research fields.

PMID- 20804242
TI  - The road to forgiveness: a meta-analytic synthesis of its situational and
      dispositional correlates.
AB  - Forgiveness has received widespread attention among psychologists from social,
      personality, clinical, developmental, and organizational perspectives alike.
      Despite great progress, the forgiveness literature has witnessed few attempts at
      empirical integration. Toward this end, we meta-analyze results from 175 studies
      and 26,006 participants to examine the correlates of interpersonal forgiveness
      (i.e., forgiveness of a single offender by a single victim). A tripartite
      forgiveness typology is proposed, encompassing victims' (a) cognitions, (b)
      affect, and (c) constraints following offense, with each consisting of
      situational and dispositional components. We tested hypotheses with respect to 22
      distinct constructs, as correlates of forgiveness, that have been measured across
      different fields within psychology. We also evaluated key sample and study
      characteristics, including gender, age, time, and methodology as main effects and
      moderators. Results highlight the multifaceted nature of forgiveness. Variables
      with particularly notable effects include intent (r = -.49), state empathy (r =
      .51), apology (r = .42), and state anger (r = -.41). Consistent with previous
      theory, situational constructs are shown to account for greater variance in
      forgiveness than victim dispositions, although within-category differences are
      considerable. Sample and study characteristics yielded negligible effects on
      forgiveness, despite previous theorizing to the contrary: The effect of gender
      was nonsignificant (r = .01), and the effect of age was negligible (r = .06).
      Preliminary evidence suggests that methodology may exhibit some moderating
      effects. Scenario methodologies led to enhanced effects for cognitions; recall
      methodologies led to enhanced effects for affect.

PMID- 20804240
TI  - Implicit affective cues and attentional tuning: an integrative review.
AB  - A large and growing number of studies support the notion that arousing positive
      emotional states expand, and that arousing negative states constrict, the scope
      of attention on both the perceptual and conceptual levels. However, these studies
      have predominantly involved the manipulation or measurement of conscious
      emotional experiences (e.g., subjective feelings of happiness or anxiety). This
      raises the question: Do cues that are merely associated with benign versus
      threatening situations but do not elicit conscious feelings of positive or
      negative emotional arousal independently expand or contract attentional scope?
      Integrating theoretical advances in affective neuroscience, positive psychology,
      and social cognition, the authors propose that rudimentary intero- and
      exteroceptive stimuli may indeed become associated with the onset of arousing
      positive or negative emotional states and/or with appraisals that the environment
      is benign or threatening and thereby come to moderate the scope of attention in
      the absence of conscious emotional experience. Specifically, implicit "benign
      situation" cues are posited to broaden, and implicit "threatening situation" cues
      to narrow, the range of both perceptual and conceptual attentional selection. An
      extensive array of research findings involving a diverse set of such implicit
      affective cues (e.g., enactment of approach and avoidance behaviors, incidental
      exposure to colors signaling safety vs. danger) is marshaled in support of this
      proposition. Potential alternative explanations for and moderators of these
      attentional tuning effects, as well as their higher level neuropsychological
      underpinnings, are also discussed along with prospective extensions to a range of
      other situational cues and domains of social cognitive processing.

PMID- 20804244
TI  - Influence of age on practice effects in longitudinal neurocognitive change.
AB  - OBJECTIVE: Longitudinal comparisons of neurocognitive functioning often reveal
      stability or age-related increases in performance among adults under about 60
      years of age. Because nearly monotonic declines with increasing age are typically
      evident in cross-sectional comparisons, there is a discrepancy in the inferred
      age trends based on the two types of comparisons. The current research
      investigated the role of practice effects in longitudinal comparisons on the
      discrepancy. METHOD: Longitudinal data over an average interval of 2.5 years were
      available on five abilities (i.e., reasoning, spatial visualization, episodic
      memory, perceptual speed, vocabulary) in a sample of 1,616 adults ranging from 18
      to over 80 years of age. Practice effects were estimated from comparisons of the
      performance of people of the same age tested for either the first or second time,
      after adjusting for the possibility of selective attrition. RESULTS: Increased
      age was associated with significantly more negative longitudinal changes with
      each ability. All of the estimated practice effects were positive, but they
      varied in magnitude across neurocognitive abilities and as a function of age.
      After adjusting for practice effects the longitudinal changes were less positive
      at younger ages and slightly less negative at older ages. CONCLUSIONS: It was
      concluded that some, but not all, of the discrepancy between cross-sectional and
      longitudinal age trends in neurocognitive functioning is attributable to practice
      effects positively biasing the longitudinal trends. These results suggest that
      the neurobiological substrates of neurocognitive functioning may change across
      different periods in adulthood.

PMID- 20804243
TI  - Testing covariates of Type 2 diabetes-cognition associations in older adults:
      moderating or mediating effects?
AB  - OBJECTIVE: The general goal of this study was to advance our understanding of
      Type 2 diabetes (T2D)-cognition relationships in older adults by linking and
      testing comprehensive sets of potential moderators, potential mediators, and
      multiple cognitive outcomes. METHOD: We identified in the literature 13 health
      related (but T2D-distal) potential covariates, representing four informal domains
      (i.e., biological vitality, personal affect, subjective health, lifestyle
      activities). Cross-sectional data from the Victoria Longitudinal Study (age range
      = 53-90 years; n = 41 T2D and n = 458 control participants) were used. We first
      examined whether any of the 13 potential covariates influenced T2D-cognition
      associations, as measured by a comprehensive neuropsychological battery (15
      measures). Next, using standard regression-based moderator and mediator analyses,
      we systematically tested whether the identified covariates would significantly
      alter observed T2D-cognition relationships. RESULTS: Six potential covariates
      were found to be sensitive to T2D associations with performance on seven
      cognitive measures. Three factors (systolic blood pressure, gait-balance
      composite, subjective health) were significant mediators. Each mediated multiple
      cognitive outcomes, especially measures of neurocognitive speed, executive
      functioning, and episodic memory. CONCLUSIONS: Our findings offer a relatively
      comprehensive perspective of T2D-related cognitive deficits, comorbidities, and
      modulating influences. The implications for future research reach across several
      fields of study and application. These include (1) neuropsychological research on
      neural and biological bases of T2D-related cognitive decline, (2) clinical
      research on intervention and treatment strategies, and (3) larger-scale
      longitudinal studies examining the potential multilateral and dynamic
      relationships among T2D status, related comorbidities, and cognitive outcomes.

PMID- 20804245
TI  - Relationship between depression, fatigue, subjective cognitive impairment, and
      objective neuropsychological functioning in patients with multiple sclerosis.
AB  - OBJECTIVE: This study explored the influence of depression and fatigue on
      subjective cognitive complaints and objective neuropsychological impairment in
      patients with multiple sclerosis (MS). METHODS: Data for this study were taken
      from a randomized controlled trial, comparing 16 weeks of telephone-administered
      cognitive-behavioral therapy and telephone-administered supportive emotion
      focused therapy for the treatment of depression. The sample includes 127 patients
      with MS. The following self-report measures were collected pre- and
      posttreatment: Perceived Deficits Questionnaire, Beck Depression Inventory-II,
      and Modified Fatigue Impact Scale. Measures of objective cognitive functioning
      and the Hamilton Rating Scale for Depression were administered over the
      telephone. RESULTS: Our results showed that changes in depression and fatigue
      significantly predicted changes in subjective cognitive complaints from pre- to
      posttreatment, with patients perceiving fewer cognitive problems at posttreatment
      (beta = .36, p < .001 and beta = .61, p < .001, respectively). Changes in
      depression and fatigue were not significantly related to changes in objective
      neuropsychological performance. Improvements in depression and fatigue also
      predicted improved accuracy in perceiving cognitive abilities from pre- to
      posttreatment (OR = .77, p < .001 and OR = .90, p < .001, respectively).
      CONCLUSIONS: The results of this study suggest that improvements in depression
      and fatigue through treatment do not influence objective neuropsychological
      performance in MS patients, but do relate to changes in subjective impairment.
      Furthermore, these changes improve patients' abilities to accurately perceive
      their cognitive functioning.

PMID- 20804247
TI  - Executive function in individuals with subthreshold autism traits.
AB  - OBJECTIVE: Recent research has documented increased psychosocial difficulties in
      individuals who report higher-than-typical autistic traits but without an Autism
      Spectrum Disorder (ASD) diagnosis. Less is known, however, regarding the
      cognitive profile of individuals with subthreshold autism symptomatology. The
      objective of the present study was to provide additional insight into this issue
      and examine whether young adults who report higher degrees of autism traits also
      report experiencing increased difficulties with executive control. METHOD: The
      Behavior Rating Inventory of Executive Function was utilized to evaluate
      behavioral aspects of executive functioning in 66 and 28 individuals who endorsed
      high and low subthreshold levels of autism symptomatology, respectively. RESULTS:
      After accounting for Attention Deficit/Hyperactivity Disorder (ADHD)
      symptomatology at both the group and individual participant levels, we found that
      autism traits continued to explain a significant amount of variance in
      participants' overall level of executive function (Global Executive Composite) as
      well as within most individual executive domains. Interestingly, the high and low
      trait groups did not differ on the inhibitory control and organization of
      materials scales, areas of functioning that appears to be largely spared in
      individuals with ASD as well. CONCLUSIONS: Findings from the present study are
      consistent with past research linking ASD and executive control impairment. In
      addition, ASD and ADHD traits were associated with unique contributions to the
      executive control profile of individuals with subthreshold autism symptomatology.
      This finding underscores the importance of accounting for ADHD symptomatology in
      studying ASD.

PMID- 20804246
TI  - The nature of naming errors in primary progressive aphasia versus acute post
      stroke aphasia.
AB  - OBJECTIVE: To compare the distribution of error types across subgroups of primary
      progressive aphasia and poststroke aphasia in different vascular locations.
      METHOD: We analyzed naming errors in 49 individuals with acute left hemisphere
      ischemic stroke and 55 individuals with three variants of primary progressive
      aphasia. Location of atrophy or ischemic stroke was characterized using MRI.
      RESULTS: We found that distribution of error types was very similar across all
      subgroups, irrespective of the site or etiology of the lesion. The only
      significant difference across groups was the percentage of circumlocutions (F(7,
      96) = 3.02, p = .005). Circumlocution errors were highest among logopenic variant
      PPA (24%) and semantic variant PPA (24%). Semantic coordinate errors were common
      in all groups, probably because they can arise from disruption of different
      cognitive processes underlying naming and, therefore, from different locations of
      brain damage. CONCLUSIONS: Semantic errors are common among all types of primary
      progressive aphasia and poststroke aphasia, and the type of error depends in part
      on the location of damage.

PMID- 20804248
TI  - Recognition by familiarity is preserved in Parkinson's without dementia and Lewy
      Body disease.
AB  - OBJECTIVE: The retrieval deficit hypothesis states that the lack of deficit in
      recognition often observed in patients with Parkinson's disease is because of the
      low retrieval requirements of the task, given that these patients have retrieval
      and not encoding deficits. To test this hypothesis we investigated recognition
      memory by familiarity in Parkinson's patients and in patients with Lewy Bodies
      disease and Parkinson with dementia. METHOD: We analyzed to what extent the
      experimental groups were able to recognize by familiarity in a typical yes/no
      recognition memory task. The experimental groups were patients with early
      nondemented Parkinson's disease, advanced nondemented Parkinson's disease,
      demented Parkinson's patients, and patients with dementia with Lewy Bodies. We
      compared their performance with a group of young and another group of old healthy
      participants. The estimation of familiarity was made by analyzing recognition of
      word targets and distractors consisting of combinations of different letters in
      comparison with a condition in which targets and distractors were composed of
      similar letters, even though subjects were unaware of the independent variable.
      RESULTS: The results indicate that familiarity was used at the same level by
      controls, patients with early Parkinson's disease and patients with dementia with
      Lewy Bodies. Although late Parkinson patients also used familiarity, its effect
      was only marginally significant. Patients with Parkinson's disease and dementia
      were not capable of using familiarity in recognition memory. CONCLUSIONS: Our
      results support the retrieval deficit hypothesis as Parkinson's patients without
      dementia show no deficit in a situation in which the retrieval requirements are
      minimal.

PMID- 20804249
TI  - Scene construction in schizophrenia.
AB  - OBJECTIVE: Recent research has revealed that schizophrenia patients are impaired
      in remembering the past and imagining the future. In this study, we examined
      patients' ability to engage in scene construction (i.e., the process of mentally
      generating and maintaining a complex and coherent scene), which is a key part of
      retrieving past experiences and episodic future thinking. METHOD: 24 participants
      with schizophrenia and 25 healthy controls were asked to imagine new fictitious
      experiences and described their mental representations of the scenes in as much
      detail as possible. Descriptions were scored according to various dimensions
      (e.g., sensory details, spatial reference), and participants also provided
      ratings of their subjective experience when imagining the scenes (e.g., their
      sense of presence, the perceived similarity of imagined events to past
      experiences). RESULTS: Imagined scenes contained less phenomenological details (d
      = 1.11) and were more fragmented (d = 2.81) in schizophrenia patients compared to
      controls. Furthermore, positive symptoms were positively correlated to the sense
      of presence (r = .43) and the perceived similarity of imagined events to past
      episodes (r = .47), whereas negative symptoms were negatively related to the
      overall richness of the imagined scenes (r = -.43). CONCLUSIONS: The results
      suggest that schizophrenic patients' impairments in remembering the past and
      imagining the future are, at least in part, due to deficits in the process of
      scene construction. The relationships between the characteristics of imagined
      scenes and positive and negative symptoms could be related to reality monitoring
      deficits and difficulties in strategic retrieval processes, respectively.

PMID- 20804250
TI  - Age-related practice effects across longitudinal neuropsychological assessments
      in older people with schizophrenia.
AB  - The relationship between aging and practice effects on longitudinal
      neuropsychological assessments was investigated in middle-aged and older people
      with schizophrenia and healthy controls. METHOD: Older people with schizophrenia
      (n = 107; M age = 56.1) and age-comparable nonpsychiatric controls (n = 107; M
      age = 57.7) were scheduled to receive annual assessments on a comprehensive
      battery of neuropsychological tests for an average of 2.5 years (range 11 months
      to 4 years). Mixed-model analyses were used to separately examine the effects of
      practice and age on test performance. RESULTS: Number of prior assessments
      (practice) was associated with significant performance improvement across
      assessments, whereas older age was associated with significant decline in
      performance. The groups did not differ significantly in extent of age-related
      cognitive decline, but a three-way interaction among group, age, and practice was
      found, such that greater age-related decline in practice effects were found for
      older people with schizophrenia relative to nonpsychiatric participants.
      CONCLUSIONS: This study did not find any evidence of neurodegenerative age
      related decline in neuropsychological abilities in middle-aged and older people
      with schizophrenia, but older age was associated with diminished ability to
      benefit from repeated exposure to cognitive tasks in people with schizophrenia.
      Cognitive impairment in schizophrenia may combine with cognitive decline
      associated with normal aging to reduce practice effects in older patients. These
      findings have important implications for the design of studies examining the
      longitudinal trajectory of cognitive functioning across the life span of people
      with schizophrenia, as well as clinical trials that attempt to demonstrate
      cognitive enhancement in these individuals.

PMID- 20804251
TI  - Data-driven methodology illustrating mechanisms underlying word list recall:
      applications to clinical research.
AB  - OBJECTIVE: Word list learning tasks such as the California Verbal Learning Test
      (CVLT; Delis, Kramer, Kaplan, & Ober, 1987) are widely used to investigate recall
      strategies. Participants who recall the most words generally employ semantic
      techniques, whereas those with poor recall (e.g., patients with schizophrenia)
      rely on serial techniques. However, these conclusions are based on formulas that
      assume that categories reflect semantic associations, bind strategy to overall
      performance, and neglect strategy changes over 5 trials. Therefore, we derived
      novel measures-independent of recall performance-to compute strategies across
      trials and identify whether diagnosis predicts recall strategy. METHOD:
      Participants were included on the basis of performance on the CVLT (i.e., total
      words recalled over 5 trials). The 50 highest and 50 lowest performers among
      healthy volunteers (n = 100) and patients with schizophrenia (n = 100) were
      selected. Novel measures of recall and transition probability were calculated and
      analyzed by permutation tests. RESULTS: Recall patterns and strategies of
      patients resembled those of controls with similar performance levels: Regardless
      of diagnosis, low performers were more likely to recall the first 2 and last 4
      items from the list; high performers increased engagement of semantically based
      transitions across the 5 trials, whereas low performers did not. CONCLUSIONS:
      Cognitive strategy must be considered independent of overall performance before
      attributing poor performance to degraded learning processes. Our results
      demonstrate the importance of departing from global scoring techniques,
      especially when working with clinical populations such as patients with
      schizophrenia for whom episodic memory deficits are a hallmark feature.

PMID- 20804253
TI  - Modeling the effects of hypoglycemia on a two-choice task in adult humans.
AB  - OBJECTIVE: Previous research has demonstrated that hypoglycemia causes reaction
      times to be slower and more variable. Reaction time tests, however, use multiple
      cognitive and noncognitive processes. This study is the first to use a validated
      sequential sampling model (diffusion model) applied to results obtained from a
      simple 2-choice task in adult humans to assess the effects of hypoglycemia on the
      basic parameters of decision making. METHOD: Fourteen adult volunteers were
      tested on a numerosity discrimination task with and without reduced blood glucose
      concentrations. The results were analyzed with a model that dissects the
      components of processing that underlie decisions: the quality of the information
      on which a decision is based (drift rate), the critical amount of evidence that
      must be accumulated before a decision is made (boundary separation), and the time
      taken by nondecision processes. RESULTS: Hypoglycemia resulted in a reduction of
      mean drift rate from 0.290 to 0.211, t(13) = 4.10, p < .05. No effect of
      experimental state was observed on the amount of evidence required to make a
      decision or peripheral and motor processes. CONCLUSION: This study locates the
      precise processing deficit associated with hypoglycemia and provides further
      understanding of the precise cognitive effect of hypoglycemia. Further research
      into the amelioration of these effects is required.

PMID- 20804252
TI  - Appraising the ANT: Psychometric and theoretical considerations of the Attention
      Network Test.
AB  - OBJECTIVE: The Attention Network Test (ANT) is a tool used to assess the
      efficiency of the 3 attention networks-alerting, orienting, and executive
      control. The ANT has become popular in the neuropsychological literature since
      its first description in 2002, with some form of the task currently appearing in
      no less than 65 original research papers. Although several general reviews of the
      ANT exist, none provide an analysis of its psychometric properties. METHOD: Data
      from 15 unique studies were collected, resulting in a large sample (N = 1,129) of
      healthy individuals. Split-half reliability, variance structure, distribution
      shape, and independence of measurement of the 3 attention network scores were
      analyzed, considering both reaction time and accuracy as dependent variables.
      RESULTS: Split-half reliabilities of reaction time based attention network scores
      were low for alerting (rweighted = .20, CI 95%weighted [.14, .27], Spearman-Brown
      r = .38) and orienting (rweighted = .32, CI 95%weighted [.26, .38], Spearman
      Brown r = .55), and moderate high for executive control (rweighted = .65, CI
      95%weighted [.61, .71], Spearman-Brown r = .81). Analysis of the variance
      structure of the ANT indicated that power to find significant effects was
      variable across networks and dependent on the statistical analysis being used.
      Both analysis of variance (significant interaction observed in 100% of 15
      studies) and correlational analyses (multiple-significant inter-network
      correlations observed) suggest that the networks measured by the ANT are not
      independent. CONCLUSIONS: In the collection, analysis and interpretation of any
      test data, psychometric properties, such as those reported here for the ANT, must
      be carefully considered.

PMID- 20804254
TI  - Laterality effects for musical structure processing: a dichotic listening study.
AB  - OBJECTIVE: Our study investigated hemispheric lateralization for musical
      structure processing using a dichotic listening paradigm with music and speech.
      METHOD: Eight chord sequences and 8 spoken syllable sequences were simultaneously
      presented, each to 1 ear. For the musical sequences, the final chord was expected
      (i.e., tonic) or less expected (i.e., subdominant). In addition to tonal
      function, which was task irrelevant, we manipulated the final syllable and the
      final timbre of the sequences for the experimental task: Participants were asked
      to identify the final syllable (/di/, /du/) or the timbre of the final chord
      (Timbre A or B). RESULTS: Our experiment revealed a left-ear advantage for the
      tonal function effect on spoken syllable identification. For syllables presented
      to the right ear, identification was faster when the final chord of the musical
      sequence was a tonic chord rather than a subdominant chord (i.e., musical
      sequences presented to the left ear). CONCLUSIONS: The present finding extends
      the effect of musical structure previously observed for sung and visual syllable
      processing to spoken syllable processing. It further suggests a right-hemispheric
      specialization for the processing of musical structures in healthy listeners, as
      previously reported for split-brain patients (Tramo & Bharucha, 1991).

PMID- 20804255
TI  - A pilot study of the neuropsychological benefits of computerized cognitive
      rehabilitation in Ugandan children with HIV.
AB  - OBJECTIVE: Because antiretroviral treatment (ART) fails to improve neurocognitive
      impairment in children with HIV, we completed a pilot study evaluating the
      feasibility and cognitive benefit of computerized cognitive rehabilitation
      therapy (CCRT) in Ugandan children with HIV. METHOD: Sixty Ugandan children with
      HIV (23 on ART) were randomly assigned to 10 sessions of Captain's Log CCRT
      (Sandford, 2007) training configured for attention and memory skills or no
      intervention. Kaufman Assessment Battery for Children (2nd ed., KABC-2; Kaufman &
      Kaufman, 2004) performance at baseline indicated pervasive neurocognitive
      impairment. Cognitive ability was assessed before and after training using the
      Cogstate computerized neuropsychological test (Darby, Maruff, Collie, &
      McStephen, 2002). Viral load along with CD4 and CD8 absolute and activation
      levels also were measured posttest. RESULTS: CCRT was well received with a 95%
      adherence rate to scheduled training sessions. CCRT intervention children showed
      greater improvement on a Cogstate card detection task of simple attention (p =
      .02), and speed of correct moves on a Groton Maze Learning Task (p < .001). These
      analyses were completed using an analysis of covariance model that adjusted
      Cogstate performance for the child's age, standardized weight for age, gender,
      socioeconomic status, school grade level, and baseline KABC-2 performance. ART
      treatment was not related to Cogstate performance or improvement as a result of
      CCRT. CD4 and CD8 activation levels were correlated with Cogstate improvement
      specifically for the CCRT group. CONCLUSIONS: CCRT was feasible with our study
      population and improved maze learning and attention on a detection task. This
      supports previous findings by our group with cerebral malaria survivors
      (Bangirana, Giordani, et al., 2009).

PMID- 20804256
TI  - The role of vision in the Corsi block-tapping task: evidence from blind and
      sighted people.
AB  - OBJECTIVE: This study aims at adapting the Corsi Block-Tapping task to measure
      serial-spatial memory in blind people and at clarifying the role of visual
      experience in the task. METHOD: Congenitally blind, adventitiously blind, and
      blindfolded sighted people were compared on a version of the Corsi board that
      allowed the haptic perception of block positions (Haptic-Corsi). Participants
      placed their fingers on the blocks that the experimenter moved upward according
      to sequences of increasing length. Afterward, participants reproduced the
      sequences in forward/backward order. RESULTS: The results showed a significant
      interaction between groups and forward/backward span: F(2, 58) = 5.74, MSE = .39,
      p < .01, eta2 = .16. In forward order the memory span was higher in
      adventitiously blind participants than blindfolded sighted (p < .05) but not
      congenitally blind participants. In backward order, there were no significant
      differences. CONCLUSIONS: The good performance of blind people, especially
      adventitiously ones, was interpreted as evidence that sequential haptic inputs
      were organized spatially. The possible cognitive processes underlying the
      performance were discussed.

PMID- 20804257
TI  - Correlates of the MMPI-2-RF in a college setting.
AB  - The current study examined empirical correlates of scores on Minnesota
      Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF; A. Tellegen &
      Y. S. Ben-Porath, 2008; Y. S. Ben-Porath & A. Tellegen, 2008) scales in a college
      setting. The MMPI-2-RF and six criterion measures (assessing anger,
      assertiveness, sex roles, cognitive failures, social avoidance, and social fear)
      were administered to 846 college students (nmen = 264, nwomen = 582) to examine
      the convergent and discriminant validity of scores on the MMPI-2-RF Specific
      Problems and Interest scales. Results demonstrated evidence of generally good
      convergent score validity for the selected MMPI-2-RF scales, reflected in large
      effect size correlations with criterion measure scores. Further, MMPI-2-RF scale
      scores demonstrated adequate discriminant validity, reflected in relatively low
      comparative median correlations between scores on MMPI-2-RF substantive scale
      sets and criterion measures. Limitations and future directions are discussed.

PMID- 20804258
TI  - The Psychopathy Checklist: Youth Version and adolescent and adult recidivism:
      considerations with respect to gender, ethnicity, and age.
AB  - The present study investigated the predictive accuracy of the Psychopathy
      Checklist: Youth Version (PCL: YV; A. E. Forth, D. S. Kosson, & R. D. Hare, 2003)
      for youth and adult recidivism, with respect to gender, ethnicity, and age, in a
      sample of 161 Canadian young offenders who received psychological services from
      an outpatient mental health facility. The PCL: YV significantly predicted any
      general, nonviolent, and violent recidivism in the aggregate sample over a 7-year
      follow-up; however, when results were disaggregated by youth and adult outcomes,
      the PCL: YV consistently appeared to be a stronger predictor of youth recidivism.
      The PCL: YV predicted youth recidivism for subsamples of female and Aboriginal
      youths, and very few differences in the predictive accuracy of the tool were
      observed for younger vs. older adolescent groups. Both the 13-item (i.e., D. J.
      Cooke & C. Michie, 2001, 3-factor) and the 20-item (i.e., R. D. Hare, 2003, 4
      factor) models appeared to predict various recidivism criteria comparably across
      the aggregate sample and within specific demographic subgroups (e.g., female and
      Aboriginal youth). The Antisocial facet contributed the most variance in the
      prediction of adult outcomes, whereas the 3-factor model contributed significant
      incremental variance in the prediction of youth recidivism outcomes. Potential
      implications concerning the use of the PCL: YV in clinical and forensic
      assessment contexts are discussed.

PMID- 20804259
TI  - Base rates of social skills acquisition/performance deficits, strengths, and
      problem behaviors: an analysis of the Social Skills Improvement System--Rating
      Scales.
AB  - Base rate information is important in clinical assessment because one cannot know
      how unusual or typical a phenomenon is without first knowing its base rate in the
      population. This study empirically determined the base rates of social skills
      acquisition and performance deficits, social skills strengths, and problem
      behaviors using a nationally representative sample of children and adolescent
      ages 3-18 years. Using the national standardization sample of the Social Skills
      Improvement System--Rating Scales (N = 4,550) across 3 informants (teacher,
      parent, and student) and across 3 broad age groupings (3-5 years, 5-12 years, and
      13-18 years), these base rates were computed. Results showed that the base rates
      for social skills acquisition deficits and problem behaviors are extremely low in
      the general population. Base rates for social skills performance deficits and
      social skills strengths were considerably higher, with students in the 5- to 12
      year-old age group reporting fewer performance deficits and more social skills
      strengths than older children (13-18 years). Teachers and parents reported more
      performance deficits and fewer social skills strengths across all age groups than
      students in the 5- to 12-year-old age group. These results are discussed in terms
      of the utility of base rate information in clinical decision making.

PMID- 20804260
TI  - Can alexithymia be assessed in adolescents? Psychometric properties of the 20
      item Toronto Alexithymia Scale in younger, middle, and older adolescents.
AB  - The 20-item Toronto Alexithymia Scale (TAS-20; Bagby, Parker, & Taylor, 1994;
      Bagby, Taylor, & Parker, 1994) is the most widely used self-report measure of the
      alexithymia construct. The TAS-20 comprises 3 factors that assess difficulty
      identifying feelings, difficulty describing feelings, and externally oriented
      thinking. Although the instrument is being increasingly used with adolescent
      respondents, the psychometric properties of the TAS-20 have not been
      systematically evaluated in preadult populations. In the present study, we
      examined measurement invariance of the factor structure, internal reliability,
      and mean levels of responses on the TAS-20 in groups of younger adolescents (aged
      13-14 years), middle adolescents (aged 15-16 years), and older adolescents (aged
      17-18 years), as well as in a comparison group of young adults (aged 19-21
      years). Formal readability analysis of the TAS-20 assessment was also conducted.
      Results revealed systematic age differences in the factor structure and
      psychometric properties of the TAS-20, with the quality of measurement
      progressively deteriorating with younger age. Much of this effect could be
      attributed to the reading difficulty of the scale. The use of the TAS-20 with
      teenage respondents is not recommended without appropriate adaptation and further
      psychometric validation. Several adaptation strategies are discussed.

PMID- 20804261
TI  - Know thyself: misperceptions of actual performance undermine achievement
      motivation, future performance, and subjective well-being.
AB  - Contrary to the popular assumption that self-enhancement improves task motivation
      and future performance, the authors propose that both inflated and deflated self
      assessments of performance are linked to an increased likelihood of practicing
      self-handicapping and having relatively poor performance in future tasks.
      Consistent with this proposal, we found that irrespective of the level of actual
      performance, compared with accurate self-assessment, both inflated and deflated
      self-assessments of task performance are associated with a greater tendency to
      (a) practice self-handicapping (Study 1: prefer to work under distraction; Study
      2: withhold preparatory effort), (b) perform relatively poorly in a subsequent
      task (Study 3), (c) have relatively low academic achievement (Study 4), and (d)
      report a relatively low level of subjective well-being (Study 5). The authors
      discuss these results in terms of their educational implications.

PMID- 20804262
TI  - O. J. Simpson as shared (and unshared) reality: the impact of consensually shared
      beliefs on interpersonal perceptions and task performance in different- and same
      ethnicity dyads.
AB  - Shared reality theory postulates that interpersonal relationships are regulated
      by the degree to which people share experiences and beliefs (Hardin & Higgins,
      1996). To assess consequences of shared (and unshared) reality for interpersonal
      relationships, we examined the effects of the 1990s Simpson trial on actual
      interpersonal interactions in same- and different-ethnicity dyads. In 3
      experiments (conducted directly following, 5 years after, and 10 years after the
      trial), people who had been primed with Simpson participated in cooperative
      problem-solving tasks. Because the trial represented a dimension of belief
      discrepancy between Blacks and Whites but a dimension of shared beliefs within
      the two ethnic groups, shared reality theory predicts that activating memories of
      the trial would affect interpersonal interactions differently depending upon
      ethnic composition of dyads. As predicted, thoughts of Simpson caused decrements
      in quality of interpersonal perceptions and behaviors for different-ethnicity
      dyads but increases for same-ethnicity dyads. In addition, in a 4th study, we
      found that consensus predicted liking among partners in the previous 3
      experiments and that these effects were significant in the expected direction for
      both same- and different-ethnicity pairs.

PMID- 20804263
TI  - Language style matching in writing: synchrony in essays, correspondence, and
      poetry.
AB  - Each relationship has its own personality. Almost immediately after a social
      interaction begins, verbal and nonverbal behaviors become synchronized. Even in
      asocial contexts, individuals tend to produce utterances that match the
      grammatical structure of sentences they have recently heard or read. Three
      projects explore language style matching (LSM) in everyday writing tasks and
      professional writing. LSM is the relative use of 9 function word categories
      (e.g., articles, personal pronouns) between any 2 texts. In the first project, 2
      samples totaling 1,744 college students answered 4 essay questions written in
      very different styles. Students automatically matched the language style of the
      target questions. Overall, the LSM metric was internally consistent and reliable
      across writing tasks. Women, participants of higher socioeconomic status, and
      students who earned higher test grades matched with targets more than others did.
      In the second project, 74 participants completed cliffhanger excerpts from
      popular fiction. Judges' ratings of excerpt-response similarity were related to
      content matching but not function word matching, as indexed by LSM. Further,
      participants were not able to intentionally increase style or content matching.
      In the final project, an archival study tracked the professional writing and
      personal correspondence of 3 pairs of famous writers across their relationships.
      Language matching in poetry and letters reflected fluctuations in the
      relationships of 3 couples: Sigmund Freud and Carl Jung, Elizabeth Barrett and
      Robert Browning, and Sylvia Plath and Ted Hughes. Implications for using LSM as
      an implicit marker of social engagement and influence are discussed. (PsycINFO
      Database Record (c) 2010 APA, all rights reserved).

PMID- 20804264
TI  - Disaster case management and individuals with disabilities.
AB  - PURPOSE: To examine the case management and disaster recovery needs of
      individuals with disabilities following Hurricane Katrina. The case managers and
      supervisors in this study provided case management to individuals with
      disabilities as part of the largest coordinated disaster case management program
      in U.S. history, the Katrina Aid Today consortium. This study provides an account
      of the disaster case management needs of individuals with disabilities as well as
      a picture of their long-term recovery process two years following the disaster.
      DESIGN: Forty-two case managers and 12 case management supervisors from this
      program provided services to a collective caseload of 2,047 individuals with
      disabilities and their families. Interviews and telephone surveys were conducted
      with these participants 20-24 months after the disaster. The qualitative data
      were analyzed using grounded theory methodology, and descriptive statistics
      summarize the demographic data. RESULTS: Findings suggest that the disaster
      recovery process is typically more complex and lengthy for individuals with
      disabilities and requires negotiation of a service system sometimes unprepared
      for disability-related needs. Barriers to disaster recovery for individuals with
      disabilities included a lack of accessible housing, transportation, and disaster
      services. Supports to disaster recovery included the individual effort and
      advocacy of a case manager, connecting with needed resources, collaboration with
      other agencies, and client motivation and persistence. IMPLICATIONS: Results
      suggest that disaster recovery is facilitated by case managers with disability
      expertise, including knowledge about the needs of individuals with disabilities
      and about disability-related services.

PMID- 20804265
TI  - Prevalence and consequences of disaster-related illness and injury from Hurricane
      Ike.
AB  - OBJECTIVE: To explore the extent to which disasters may be a source of injury and
      disability in community populations, we examined the prevalence and short-term
      consequences of disaster-related illness and injury for distress, disability, and
      perceived needs for care. DESIGN: A random population survey was conducted 2-6
      months after Hurricane Ike struck Galveston Bay on September 13, 2008.
      PARTICIPANTS: The sample was composed of 658 adults representative of Galveston
      and Chambers Counties, Texas. RESULTS: The prevalences of personal injury (4%)
      and household illness (16%) indicated that approximately 7,700 adults in the two
      county area were injured, and another 31,500 adults experienced household-level
      illness. Risk for injury/illness increased with area damage and decreased with
      evacuation. In bivariate tests, injury or illness or both were related to all
      outcome measures. In multivariate analyses that controlled for co-occurring
      stressors representing trauma, loss, adversities, and community effects, injury
      or illness or both were associated with global stress, posttraumatic stress,
      dysfunction, days of disability, and perceived needs for care, but not with
      depression or anxiety. CONCLUSIONS: The associations of injury with distress and
      disability suggest that community programs should reach out to injured persons
      for early mental health and functional assessments and, where indicated,
      intervene in ways that reduce further disability and need for complex
      rehabilitative services. The results also point to the potential effectiveness of
      evacuation incentives with regard to the prevention of disaster-related injury
      and disability.

PMID- 20804266
TI  - The psychosocial impact of Hurricane Katrina on persons with disabilities and
      independent living center staff living on the American Gulf Coast.
AB  - OBJECTIVES: To determine the impact of Hurricane Katrina on the psychosocial
      health of people with disabilities and on the ability of people with disabilities
      in the affected area to live independently. PARTICIPANTS: Transcribed
      conversations were analyzed for 56 survivors of Hurricane Katrina on the American
      Gulf Coast, all of whom were persons with disabilities or persons working with
      them. METHOD: Semi-structured interviews were conducted either individually or in
      focus groups with participants. Qualitative analysis was undertaken using
      hermeneutic techniques. RESULTS: Six major themes emerged: faith,
      incredulousness, blaming others or oneself, family adaptation and resiliency, and
      work and professional responsibility. CONCLUSIONS: The resiliency of persons with
      disabilities to adapt to disasters can be better understood through factors such
      as these, providing an effective barometer of social capital that can help
      societies prepare for future disasters among those most vulnerable.

PMID- 20804267
TI  - A tale of two studies of two disasters: comparing psychosocial responses to
      disaster among Oklahoma City bombing survivors and Hurricane Katrina evacuees.
AB  - PURPOSE: An accumulation of disaster mental health research literature in the
      last few decades has contributed knowledge to direct disaster mental health
      interventions. However, no single set of principles can necessarily outline all
      anticipated mental health needs to be encountered in a particular disaster.
      METHODS: To illustrate how different disaster scenarios may yield a divergence of
      mental health needs, this article compares mental health findings from two
      distinctly different studies of two very different populations affected by two
      very different disasters: directly exposed survivors the Oklahoma City bombing
      and sheltered evacuees from Hurricane Katrina. RESULTS: Research on the two
      disasters reviewed illustrates many facets and complexities of postdisaster
      mental health needs in different populations in different settings after
      different types of disasters. The major findings of the Oklahoma City bombing
      study related to posttraumatic stress disorder and the main findings of the
      Hurricane Katrina study involved need for treatment of preexisting chronic mental
      health and substance abuse problems. CONCLUSION: The disaster studies in this
      review diverged in type of disaster, affected populations, setting, and timing of
      the study, and these studies yielded a divergence of findings. One disaster
      mental health model clearly cannot adequately describe all postdisaster
      scenarios.

PMID- 20804268
TI  - Emergency preparedness as a continuous improvement cycle: perspectives from a
      postacute rehabilitation facility.
AB  - OBJECTIVES: To describe the iterative process of emergency planning and
      preparedness: risk assessment, planning, rehearsal, implementation, and
      refinement. DESIGN: A narrative reflection of two complete facility evacuations
      in advance of major hurricanes in 2005 (hurricane Rita) and 2008 (hurricane Ike)
      conducted by a postacute rehabilitation facility located on the Texas gulf coast.
      PARTICIPANTS: Facility staff involved in the evacuation and ongoing care post
      evacuation, and adults with moderate to severe acquired brain injury receiving
      residential postacute rehabilitation and long-term care services. RESULTS:
      Experiences from two evacuations revealed that planning and preparation beyond
      what is required by licensing and accrediting agencies is necessary; attending to
      the needs of staff during and after and the emergency is a critical component of
      planning and preparedness; and the necessity of incorporating "lessons learned"
      into refinement of emergency preparedness plans. CONCLUSIONS: Facilities
      providing residential services to persons with neurological injury are
      potentially vulnerable to a number of natural and manmade disasters. Careful
      planning, preparation, and practice are necessary to ensure safe evacuation of
      persons served and facility personnel in response to an emergency. Experiences
      (i.e., "lessons learned") from each evacuation, subsequent changes to emergency
      preparedness plans, and recommendations for emergency preparedness beyond a
      natural disaster, such as a hurricane, are presented.

PMID- 20804269
TI  - Comorbid anxiety disorders and treatment of depression in people with multiple
      sclerosis.
AB  - OBJECTIVE: Anxiety is highly comorbid with depression, but little is known about
      the impact of anxiety disorders on the effectiveness of empirically supported
      psychotherapies for depression. We examined such outcomes for people with
      Multiple Sclerosis (MS) and depression, with versus without comorbid anxiety
      disorders. DESIGN: Participants with MS (N = 102) received 16 weeks of telephone
      administered psychotherapy for depression and were followed for one year post
      treatment. RESULTS: Participants with comorbid anxiety disorders improved to a
      similar degree during treatment as those without anxiety disorders. Outcomes
      during follow-up were mixed, and thus we divided the anxiety diagnoses into
      distress and fear disorders. The distress disorder (GAD) was associated with
      elevated anxiety symptoms during and after treatment. In contrast, fear disorders
      (i.e., panic disorder, agoraphobia, social phobia, specific phobia) were linked
      to depression, specifically during follow-up, across 3 different measures.
      CONCLUSIONS: People with GAD receiving treatment for depression may benefit from
      additional services targeting anxiety more specifically, while those with
      comorbid fear disorders may benefit from services targeting maintenance of gains
      after treatment.

PMID- 20804270
TI  - Development of a safety awareness group intervention for women with diverse
      disabilities: a pilot study.
AB  - OBJECTIVE: Describe the development and preliminary evaluation of a safety
      awareness program for women with disabilities. DESIGN: Baseline and
      postintervention questionnaires administered to a sample of women who completed a
      safety awareness program. PARTICIPANTS: Seven women with diverse disabilities.
      INTERVENTION: Eight interactive sessions designed to increase protective factors.
      SETTING: Community site for persons with disabilities. MAIN OUTCOMES: Safety self
      efficacy, safety skills, social support/isolation, and safety promoting
      behaviors. RESULTS: Significant increases from baseline to postintervention were
      found on measures of self-efficacy and safety skills. Although not statistically
      significant, improvements were also found in safety promoting behavior.
      CONCLUSION: Despite the small sample, findings suggest that participation in a
      safety awareness program may improve protective factors.

PMID- 20804271
TI  - Reporting results of latent growth modeling and multilevel modeling analyses:
      some recommendations for rehabilitation psychology.
AB  - OBJECTIVE: There has been a general increase in interest and use of modeling
      techniques that treat data as nested, whether it is people nested within larger
      units, such as families or treatment centers, or observations nested under
      people. The popularity can be witnessed by noting the number of new textbooks and
      articles related to latent growth curve modeling and multilevel modeling. This
      paper discusses both of these techniques in the context of longitudinal research
      designs, with the main purposes of highlighting some benefits and issues related
      to the use of these models and outlining guidelines for reporting results from
      studies using multilevel modeling or latent growth modeling. IMPLICATIONS: These
      longitudinal analytic techniques can be greatly beneficial to researchers
      conducting rehabilitation studies, but there are several issues related to their
      use and reporting that need to be taken into consideration.

PMID- 20804272
TI  - A longitudinal examination of the parent-child distress relationship in children
      with juvenile rheumatic disease.
AB  - OBJECTIVE: To examine the longitudinal relationships between parent and child
      distress in a sample of children with juvenile rheumatic diseases (JRDs). DESIGN:
      Cross-lagged panel correlation analysis tested the temporal precedence of parent
      distress versus child distress over a 1-year period. PARTICIPANTS: Thirty-seven
      children (ages 9-17 years; 22 girls) diagnosed with JRD and their parents
      completed self-report measures on 2 occasions (assessment interval M = 12
      months). PRIMARY OUTCOME MEASURES: Child Depression Inventory and Brief Symptom
      Inventory. RESULTS: Significant cross-sectional parent-child distress
      associations were observed at both time points. Moreover, Time 1 parent distress
      predicted child distress at Time 2 after child-reported functional ability was
      controlled; Time 1 child distress was unrelated to Time 2 parent distress. Cross
      lagged panel correlations demonstrated the temporal precedence of parent distress
      relative to child distress in the parent-child distress relationship.
      CONCLUSIONS: These preliminary findings underscore the importance of parent
      distress in parent-child transactional adjustment, and suggest a predominant role
      for parent distress in children's adjustment to JRDs.

PMID- 20804273
TI  - The reliability and validity of the Community Integration Measure in persons with
      traumatic brain injury.
AB  - OBJECTIVE: To investigate the psychometric properties of the Community
      Integration Measure (CIM), a scale that assesses self-perceived quality of
      community integration, among persons with traumatic brain injury (TBI). METHOD:
      Persons (N = 279) with TBI completed the CIM, as well as other measures of
      community integration and quality of life, and were followed up to 15 years
      postinjury. RESULTS: The CIM was found to be a reliable instrument with adequate
      internal consistency. Validity was demonstrated in its relationship to other
      measures of community integration and life satisfaction. Utility was evident in
      its prediction of perceived social support. CONCLUSION: Results suggest that the
      CIM is an adequate measure of community integration for persons with histories of
      TBI of up to 15 years.

PMID- 20804274
TI  - Attitudes toward people with disabilities: the perspective of attachment theory.
AB  - OBJECTIVE: Attachment theory was employed as the theoretical framework for the
      purpose of examining attitudes toward people with disabilities. METHOD: A total
      of 404 Jewish Israeli students without disabilities completed the
      Multidimensional Attitudes Scale Toward Persons With Disabilities (MAS) and the
      Experiences in Close Relationships Scale (ECR). RESULTS: Reading a scenario about
      an encounter with a person with a disability gave rise to more negative emotions
      than reading a similar scenario about an encounter with a person without a
      disability, regardless of participants' attachment orientations. However,
      attachment orientations moderated participants' positive cognitions and
      distancing behaviors. CONCLUSIONS: Findings suggest a dynamic process of self
      regulation when reacting to a written scenario about people with disabilities.
      This process consists of an initial spontaneous negative emotional response
      accompanied by compensatory positive cognitions and behavioral tendencies.

PMID- 20804275
TI  - The detection of malingered pain-related disability with the Personality
      Assessment Inventory.
AB  - OBJECTIVE: This study presents and evaluates a method to detect malingered pain
      related disability (MPRD) using the Personality Assessment Inventory (PAI), a
      multiscale self-report instrument with a number of useful applications in pain
      assessment. METHOD: In this study PAI scores from respondents in a chronic pain
      clinic (N = 317) and college students instructed to feign chronic pain (N = 152)
      were compared. RESULTS: Although existing PAI validity indicators demonstrated
      strong effects in discriminating actual pain and MPRD cases, these indicators
      were not sufficiently sensitive to feigned pain to recommend for clinical
      practice. A discriminant function was developed and cross-validated, which
      improved upon the sensitivity of the other indicators and yielded an overall hit
      rate of 88% for detecting individuals instructed to malinger pain-related
      disability. CONCLUSION: These data suggest that this new PAI indicator holds some
      promise for more effective detection of MPRD.

PMID- 20804276
TI  - Public policy: extending psychology's contributions to national priorities.
AB  - OVERVIEW: Much of today's psychological research and practice is relevant to our
      national health agenda and can serve the public interest. President Obama's
      landmark health care reform success provides an unprecedented opportunity to
      revolutionize society's definition of "quality care" and highlight
      rehabilitation's potential. Advocacy, vision, and a public policy presence with
      persistence are critical. Those involved often focus exclusively upon specific
      issues (e.g., reimbursement, research funding, or graduate student support).
      SUMMARY: By developing a "bigger picture" approach addressing society's real
      needs and embracing the changes technology will ultimately bring, psychology can
      have a more lasting impact. There are unlimited opportunities to advance the
      profession through personal involvement in the public policy arena. It is
      essential that psychology's next generation receives relevant mentoring.

PMID- 20804277
TI  - Temporal bisection in 4-month-old infants.
AB  - The present study was the first to investigate infants' ability to discriminate
      time using a bisection task that has been extensively used with animals and human
      adults. Infants aged 4 months were presented with two standard auditory signals,
      one short (S = 500 ms) and one long (L = 1,500 ms), and were trained either to
      look to the left after S and to the right after L, or vice versa. During the test
      phase, the infants were then presented with intermediate durations without
      reinforcement as well as the two reinforced standard durations, for which the
      reinforcement was either immediate or delayed of 3 s. The times spent by the
      infants looking to the right, left or away from the target after the stimulus
      duration were coded by two blind coders. The results revealed an orderly
      psychophysical function with the proportion of long responses increasing with
      signal duration. The point of subjective equality (Bisection Point) was closer to
      the geometric mean of the short and long standard duration than to their
      arithmetic mean. Modeling using the scalar timing models revealed that our
      infants had a relatively high sensitivity to time but that their temporal
      performance was affected by the fact that they made a large number of random
      responses. The development of the perception of time is discussed in the light of
      similarities and differences in temporal bisection performance between different
      species (rats and humans) and the different levels of development observed within
      a given species.

PMID- 20804278
TI  - Familiarity for associations? A test of the domain dichotomy theory.
AB  - Episodic recognition memory is mediated by functionally separable retrieval
      processes, notably familiarity (a general sense of prior exposure) and
      recollection (the retrieval of contextual details), whose relative engagement
      depends partly on the nature of the information being retrieved. Currently, the
      specific contribution of familiarity to associative recognition memory (where
      retrieval of the relationships between pairs of stimuli is required) is not
      clearly understood. In this study, we tested domain dichotomy theory, which
      predicts that familiarity should contribute more to associative memory when
      stimuli are similar (within-domain) than when they are distinct (between-domain).
      Participants studied stimulus pairs, and at test, discriminated intact from
      rearranged pairs. Stimuli were either within-domain (name-name or image-image
      pairs) or between-domain (name-image pairs). Across experiments we used 2
      different behavioral measures of familiarity based on receiver operating
      characteristic curves and a modified remember-know procedure. Both experiments
      provided evidence that familiarity can contribute to associative recognition;
      however, familiarity was stronger for between-domain pairs, in direct contrast to
      the domain dichotomy prediction.

PMID- 20804279
TI  - Test-enhanced learning of natural concepts: effects on recognition memory,
      classification, and metacognition.
AB  - Three experiments examined testing effects on learning of natural concepts and
      metacognitive assessments of such learning. Results revealed that testing
      enhanced recognition memory and classification accuracy for studied and novel
      exemplars of bird families on immediate and delayed tests. These effects depended
      on the balance of study and test trials during training. Metacognitive measures
      provided results suggesting that participants were aware of the beneficial
      effects of testing. A new measure of metacognition at the level of categories is
      introduced and shown to be potentially useful for theory and applied purposes. It
      is argued that focusing on optimizing the learning of natural concepts encourages
      the convergence of theorizing about memory, concept learning, and metacognition
      and holds promise for the development of applications to education.

PMID- 20804280
TI  - Global similarity predicts dissociation of classification and recognition:
      evidence questioning the implicit-explicit learning distinction in amnesia.
AB  - Dissociation of classification and recognition in amnesia is widely taken to
      imply 2 functional systems: an implicit procedural-learning system that is spared
      in amnesia and an explicit episodic-learning system that is compromised. We argue
      that both tasks reflect the global similarity of probes to memory. In
      classification, subjects sort unstudied grammatical exemplars from lures, whereas
      in recognition, they sort studied grammatical exemplars from lures. Hence, global
      similarity is necessarily greater in recognition than in classification.
      Moreover, a grammatical exemplar's similarity to studied exemplars is a nonlinear
      function of the integrity of the data in memory. Assuming that data integrity is
      better for control subjects than for subjects with amnesia, the nonlinear
      relation combined with the advantage for recognition over classification predicts
      the dissociation of recognition and classification. To illustrate the
      dissociation of recognition and classification in healthy undergraduates, we
      manipulated study time to vary the integrity of the data in memory and brought
      the dissociation under experimental control. We argue that the dissociation
      reflects a general cost in memory rather than a selective impairment of separate
      procedural and episodic systems.

PMID- 20804282
TI  - Evidence for direct retrieval of relative quantity information in a quantity
      judgment task: decimals, integers, and the role of physical similarity.
AB  - Participants' reaction times (RTs) in numerical judgment tasks in which one must
      determine which of 2 numbers is greater generally follow a monotonically
      decreasing function of the numerical distance between the two presented numbers.
      Here, I present 3 experiments in which the relative influences of numerical
      distance and physical similarity are assessed in just such a task using integers
      and decimals as stimuli. The data reveal that numerical distance is the primary
      feature controlling participants' RTs when integers are presented. However, the
      physical similarity between the decade place of the standard and the probe is the
      primary feature controlling participants' RTs when decimals are presented. I
      conclude that the unique qualities of decimals do not lend themselves to share
      the place-coding representation of integers, thus a direct retrieval mechanism
      for judging the relative quantity of decimals has developed.

PMID- 20804281
TI  - Loss of visual working memory within seconds: the combined use of refreshable and
      non-refreshable features.
AB  - We reexamine the role of time in the loss of information from working memory, the
      limited information accessible for cognitive tasks. The controversial issue of
      whether working memory deteriorates over time was investigated using arrays of
      unconventional visual characters. Each array was followed by a postperceptual
      mask, a variable retention interval (RI), and a recognition probe character.
      Dramatic forgetting across an unfilled RI of up to 6 s was observed. Adding a
      distracting task during the RI (repetition, subtraction, or parity judgment using
      spoken digits) lowered the level of recall but not increasingly so across RIs.
      Also, arrays of English letters were not forgotten during the RI unless
      distracting stimuli were included, in contrast to the finding for unconventional
      characters. The results suggest that unconventional visual items include some
      features inevitably lost over time. Attention-related processing, however,
      assists in the retention of other features and of English letters. We identify
      important constraints for working memory theories and propose that an equilibrium
      between forgetting and reactivation holds but only for elements that are not
      inevitably lost over time.

PMID- 20804283
TI  - Priming by NUMB3R5 does not involve top-down feedback.
AB  - Using the same-different task, Perea, Dunabeitia, Pollatsek, and Carreiras (2009)
      showed that digits resembling letters ("leet digits"; e.g., 1 = I, 4 = A) primed
      pseudoword strings (e.g., V35Z3D-VESZED), but letters resembling digits ("leet
      letters") did not prime digit strings (e.g., 9ES7E2-935732), and suggested that
      this is due to top-down feedback available for letter, but not digit, strings.
      Here we show that (a) single letters show as much leet priming as 3-letter words
      (Experiment 1); (b) leet priming is equally robust for digit strings and
      pseudowords when the string is 4 items long but not when 6 items long (Experiment
      2); and (c) with 6-item strings, orthotactically illegal letter strings (e.g.,
      OIAUEQ) behave just like digit strings (Experiment 3). These results indicate
      that the asymmetry in leet priming is not due to top-down feedback available
      selectively for letter strings. We offer an alternative explanation based on the
      Bayesian reader account of masked priming proposed by Norris and Kinoshita
      (2008), and the role played by the orthotactic knowledge used to extend the
      functional capacity of visual working memory involved in performing the same
      different task.

PMID- 20804284
TI  - The production effect in memory: evidence that distinctiveness underlies the
      benefit.
AB  - The production effect is the substantial benefit to memory of having studied
      information aloud as opposed to silently. MacLeod, Gopie, Hourihan, Neary, and
      Ozubko (2010) have explained this enhancement by suggesting that a word studied
      aloud acquires a distinctive encoding record and that recollecting this record
      supports identifying a word studied aloud as "old." This account was tested using
      a list discrimination paradigm, where the task is to identify in which of 2
      studied lists a target word was presented. The critical list was a mixed list
      containing words studied aloud and words studied silently. Under the
      distinctiveness explanation, studying an additional list all aloud should disrupt
      the production effect in the critical list because remembering having said a word
      aloud in the critical list will no longer be diagnostic of list status. In
      contrast, studying an additional list all silently should leave the production
      effect in the critical list intact. These predictions were confirmed in 2
      experiments.

PMID- 20804285
TI  - Determiner selection in romance languages: evidence from French.
AB  - Determiner selection requires the retrieval of the noun's syntactic features
      (e.g., gender) and sometimes of its phonological features. Miozzo and Caramazza
      (1999) argued that the selection of determiners in Germanic languages is more
      straightforward than in Romance languages because it is not dependent on the
      phonological properties of the following word. In the present study, we used the
      picture-word interference paradigm to investigate the dependency of the
      determiner on the noun's features in French. In 3 experiments, we found a gender
      congruency effect at +200 stimulus onset asynchrony (SOA), indicating that
      participants were slower to produce the name of a picture (determiner + noun)
      when the picture-word pair was incongruent in gender than when it was congruent.
      We failed to replicate this effect at 0 SOA, in line with previous studies
      (Alario & Caramazza, 2002). Our results suggest that the features involved in
      determiner selection are not language specific but rather are specific to the
      determiner system.

PMID- 20804286
TI  - The influence of type and token frequency on the acquisition of affixation
      patterns: implications for language processing.
AB  - Rules, and exceptions to such rules, are ubiquitous in many domains, including
      language. Here we used simple artificial grammars to investigate the influence of
      2 factors on the acquisition of rules and their exceptions, namely type frequency
      (the relative numbers of different exceptions to different regular items) and
      token frequency (the number of exception tokens relative to the number of regular
      tokens). We familiarized participants to either a prefixation pattern (where
      regulars started with /ZaI/ and exceptions ended with /ZaI/) or a suffixation
      pattern (where regulars ended with /ZaI/ and exceptions started with /ZaI/). We
      show that the type and the token frequency of regular items and exceptions
      influence in different ways what participants can learn. For the exceptions to be
      learned, they have to occur sufficiently often so that participants can memorize
      them; this can be achieved by a high token frequency. However, a high token
      frequency of the exceptions also impaired the acquisition of the regular pattern.
      In contrast, the type frequency of the patterns seemed to determine whether the
      regular pattern could be learned: When the type frequency of the regular items
      was sufficiently high, participants successfully learned the regular pattern even
      when the exceptions were played so often that 66% of the familiarization items
      were exceptions. We discuss these findings in the context of general learning
      mechanisms and the role they may play in language acquisition.

PMID- 20804287
TI  - Spinning in the scanner: neural correlates of virtual reorientation.
AB  - Recent studies have used spatial reorientation task paradigms to identify
      underlying cognitive mechanisms of navigation in children, adults, and a range of
      animal species. Despite broad interest in this task across disciplines, little is
      known about the brain bases of reorientation. We used functional magnetic
      resonance imaging to examine neural activity in adults during a virtual reality
      version of the reorientation task. Three environments that varied in the cues
      provided were studied: a rectangular room with 4 identical gray walls (Geometry),
      a square room with 3 gray walls and 1 red wall (Feature), and a rectangular room
      with 3 gray walls and 1 red wall (Feature + Geometry). Multiple areas within the
      medial temporal lobe (MTL) showed increased activation when a feature was present
      compared with when reorientation was based only on geometric cues. In contrast,
      reliance on geometric cues significantly activated a number of non-MTL
      structures, including the prefrontal cortex and inferior temporal gyrus. These
      results provide neural evidence for processing differences between the 2 types of
      cue as well as insight into developmental and comparative aspects of
      reorientation.

PMID- 20804288
TI  - Tracking the time course of orthographic information in spoken-word recognition.
AB  - Two visual-world experiments evaluated the time course and use of orthographic
      information in spoken-word recognition using printed words as referents.
      Participants saw 4 words on a computer screen and listened to spoken sentences
      instructing them to click on one of the words (e.g., Click on the word bead). The
      printed words appeared 200 ms before the onset of the spoken target word. In
      Experiment 1, the display included the target word and a competitor with either a
      lower degree (e.g., bear) or a higher degree (e.g., bean) of phonological overlap
      with the target. Both competitors had the same degree of orthographic overlap
      with the target. There were more fixations to the competitors than to unrelated
      distractors. Crucially, the likelihood of fixating a competitor did not vary as a
      function of the amount of phonological overlap between target and competitor. In
      Experiment 2, the display included the target word and a competitor with either a
      lower degree (e.g., bare) or a higher degree (e.g., bear) of orthographic overlap
      with the target. Competitors were homophonous and thus had the same degree of
      phonological overlap with the target. There were more fixations to higher overlap
      competitors than to lower overlap competitors, beginning during the temporal
      interval where initial fixations driven by the vowel are expected to occur. The
      authors conclude that orthographic information is rapidly activated as a spoken
      word unfolds and is immediately used in mapping spoken words onto potential
      printed referents.

PMID- 20804289
TI  - Repeated testing produces superior transfer of learning relative to repeated
      studying.
AB  - The present research investigated whether test-enhanced learning can be used to
      promote transfer. More specifically, 4 experiments examined how repeated testing
      and repeated studying affected retention and transfer of facts and concepts.
      Subjects studied prose passages and then either repeatedly restudied or took
      tests on the material. One week later, they took a final test that had either the
      same questions (Experiment 1a), new inferential questions within the same
      knowledge domain (Experiments 1b and 2), or new inferential questions from
      different knowledge domains (Experiment 3). Repeated testing produced superior
      retention and transfer on the final test relative to repeated studying. This
      finding indicates that the mnemonic benefits of test-enhanced learning are not
      limited to the retention of the specific response tested during initial learning
      but rather extend to the transfer of knowledge in a variety of contexts.

PMID- 20804290
TI  - Loss of cognitive skill across delays: constraints for theories of cognitive
      skill acquisition.
AB  - Mastering a cognitive skill requires many practice sessions, occurring over a
      period of days, weeks, months, or even years. Although a large body of research
      describes and explains gains made within a given practice session, few studies
      have investigated what happens to these gains across a delay, and none have
      examined effects of delays on item-general gains. Across 3 experiments,
      participants performed alphabet arithmetic verification in an initial practice
      session followed by a test session after a delay (from 0 to 30 days). All
      experiments included conditions yielding item-general practice gains; Experiments
      2-3 also included an item-specific practice condition. Surprisingly, item-general
      gains were relatively well preserved across a delay (e.g., only 6.7% decrease in
      practice effects after 2 days), whereas item-specific gains showed sizeable
      losses across a delay (e.g., 25.9% loss after 2 days). Results provide important
      empirical constraints to theories of cognitive skill acquisition.

PMID- 20804291
TI  - Semantic preview benefit in eye movements during reading: A parafoveal fast
      priming study.
AB  - Eye movements in reading are sensitive to foveal and parafoveal word features.
      Whereas the influence of orthographic or phonological parafoveal information on
      gaze control is undisputed, there has been no reliable evidence for early
      parafoveal extraction of semantic information in alphabetic script. Using a novel
      combination of the gaze-contingent fast-priming and boundary paradigms, we
      demonstrate semantic preview benefit when a semantically related parafoveal word
      was available during the initial 125 ms of a fixation on the pretarget word
      (Experiments 1 and 2). When the target location was made more salient,
      significant parafoveal semantic priming occurred only at 80 ms (Experiment 3).
      Finally, with short primes only (20, 40, 60 ms), effects were not significant but
      were numerically in the expected direction for 40 and 60 ms (Experiment 4). In
      all experiments, fixation durations on the target word increased with prime
      durations under all conditions. The evidence for extraction of semantic
      information from the parafoveal word favors an explanation in terms of parallel
      word processing in reading.

PMID- 20804292
TI  - Causal status and coherence in causal-based categorization.
AB  - Research has documented two effects of interfeature causal knowledge on
      classification. A causal status effect occurs when features that are causes are
      more important to category membership than their effects. A coherence effect
      occurs when combinations of features that are consistent with causal laws provide
      additional evidence of category membership. In this study, we found that stronger
      causal relations led to a weaker causal status effect and a stronger coherence
      effect (Experiment 1), that weaker alternative causes led to stronger causal
      status and coherence effects (Experiment 2), and that "essentialized" categories
      led to a stronger causal status effect (Experiment 3), albeit only for
      probabilistic causal links (Experiment 4). In addition, the causal status effect
      was mediated by features' subjective category validity, the probability they
      occur in category members. These findings were consistent with a generative model
      of categorization but inconsistent with an alternative model.

PMID- 20804293
TI  - Examining the relationship between free recall and immediate serial recall: the
      effects of list length and output order.
AB  - In 4 experiments, participants were presented with lists of between 1 and 15
      words for tests of immediate memory. For all tasks, participants tended to
      initiate recall with the first word on the list for short lists. As the list
      length was increased, so there was a decreased tendency to start with the first
      list item; and, when free to do so, participants showed an increased tendency to
      start with one of the last 4 list items. In all tasks, the start position
      strongly influenced the shape of the resultant serial position curves: When
      recall started at Serial Position 1, elevated recall of early list items was
      observed; when recall started toward the end of the list, there were extended
      recency effects. These results occurred under immediate free recall (IFR) and
      different variants of immediate serial recall (ISR) and reconstruction of order
      (RoO) tasks. We argue that these findings have implications for the relationship
      between IFR and ISR and between rehearsal and recall.

PMID- 20804294
TI  - Mental subtraction in high- and lower skilled arithmetic problem solvers: verbal
      report versus operand-recognition paradigms.
AB  - The authors used the operand-recognition paradigm (C. Thevenot, M. Fanget, & M.
      Fayol, 2007) in order to study the strategies used by adults to solve subtraction
      problems. This paradigm capitalizes on the fact that algorithmic procedures
      degrade the memory traces of the operands. Therefore, greater difficulty in
      recognizing them is expected when calculations have been solved by reconstructive
      strategies rather than by retrieval of number facts from long-term memory. The
      present results suggest that low- and high-skilled individuals differ in their
      strategy when they solve problems involving minuends from 11 to 18. Whereas high
      skilled individuals retrieve the results of such subtractions from long-term
      memory, lower skilled individuals have to resort to reconstructive strategies.
      Moreover, the authors directly confront the results obtained with the operand
      recognition paradigm and those obtained with the more classical method of verbal
      report collection and show clearly that this second method of investigation fails
      to reveal this differential pattern. The rationale behind the operand-recognition
      paradigm is then discussed.

PMID- 20804295
TI  - Embedded words in visual word recognition: does the left hemisphere see the rain
      in brain?
AB  - To examine whether interhemispheric transfer during foveal word recognition
      entails a discontinuity between the information presented to the left and right
      of fixation, we presented target words in such a way that participants fixated
      immediately left or right of an embedded word (as in gr*apple, bull*et) or in the
      middle of an embedded word (grapp*le, bu*llet). Categorization responses to
      target words were faster and more accurate in a congruent condition (in which the
      embedded word was associated with the same response; e.g., Does bullet refer to
      an item of clothing?) than in an incongruent condition (e.g., Does bullet refer
      to a type of animal?). However, the magnitude of this effect did not vary as a
      function of position of fixation, relative to the embedded word, as might be
      expected if information from the 2 visual fields was initially split over the
      cerebral hemispheres and integrated only late in the word identification process.
      Equivalent results were observed in Experiment 1 (long stimulus duration) and
      Experiment 2 (in which stimulus duration was 200 ms; i.e., less than the time
      required to initiate a refixation).

PMID- 20804296
TI  - Making things difficult in lexical decision: the impact of pseudohomophones and
      transposed-letter nonwords on frequency and semantic priming effects.
AB  - Performance in a lexical decision task is crucially dependent on the difficulty
      of the word-nonword discrimination. More wordlike nonwords cause not only a
      latency increase for words but also, as reported by Stone and Van Orden (1993),
      larger word frequency effects. Several current models of lexical decision making
      can explain these types of results in terms of a single mechanism, a mechanism
      driven by the nature of the interactions within the lexicon. In 2 experiments, we
      replicated Stone and Van Orden's increased frequency effect using both
      pseudohomophones (e.g., BEEST) and transposed-letter nonwords (e.g., JUGDE) as
      the more wordlike nonwords. In a 3rd experiment, we demonstrated that simply
      increasing word latencies without changing the difficulty of the word-nonword
      discrimination does not produce larger frequency effects. These results are
      reasonably consistent with many current models. In contrast, neither
      pseudohomophones nor transposed-letter nonwords altered the size of semantic
      priming effects across 4 additional experiments, posing a challenge to models
      that would attempt to explain both nonword difficulty effects and semantic
      priming effects in lexical decision tasks in terms of a single, lexically driven
      mechanism.

PMID- 20804298
TI  - Imagined positive emotions and inhibitory control: the differentiated effect of
      pride versus happiness.
AB  - Inhibitory control is a cognitive mechanism that contributes to successful self
      control (i.e., adherence to a long-term goal in the face of an interfering short
      term goal). This research explored the effect of imagined positive emotional
      events on inhibition. The authors proposed that the influence of imagined
      emotions on inhibition depends on whether the considered emotion corresponds to
      the attainment of a long-term goal (i.e., pride) or a short-term goal (i.e.,
      happiness). The authors predicted that in an antisaccade task that requires
      inhibition of a distractor, imagining a happiness-eliciting event is likely to
      harm inhibitory processes compared with imagining a pride-eliciting event,
      because the former but not the latter primes interfering short-term goals. The
      results showed that imagining a happiness-eliciting event decreased inhibition
      relative to imagining a pride-eliciting event. The results suggest a possible
      mechanism underlying the role of imagined positive emotions in pursuit of goals
      that require self-control.

PMID- 20804299
TI  - Revisiting the novelty effect: when familiarity, not novelty, enhances memory.
AB  - Reports of superior memory for novel relative to familiar material have figured
      prominently in recent theories of memory. However, such novelty effects are
      incongruous with long-standing observations that familiar items are remembered
      better. In 2 experiments, we explored whether this discrepancy was explained by
      differences in the type of familiarity under consideration or by differences in
      the difficulty of discriminating targets from lures, which may lead to source
      confusion for familiar but not novel targets. In Experiment 1, we directly tested
      whether previously observed novelty effects were the result of novelty,
      discrimination demands, or both. We used linguistic materials (proverbs) to
      replicate the novelty effect but found that it occurred only when familiar items
      were subject to source confusion. In Experiment 2, to examine better how novelty
      influences episodic memory, we used experimentally familiar, pre-experimentally
      familiar, and novel proverbs in a paradigm designed to overcome discrimination
      demand confounds. Memory was better for both types of familiar proverbs. These
      results indicate that familiarity, not novelty, leads to better episodic memory
      for studied items, regardless of whether familiarity is experimentally induced or
      based on prior semantic knowledge. We argue that proposals that state that
      information is encoded better if it is novel are based on over-generalizations of
      effects arising from the distinctiveness of novel materials.

PMID- 20804297
TI  - Information-processing alternatives to holistic perception: identifying the
      mechanisms of secondary-level holism within a categorization paradigm.
AB  - Failure to selectively attend to a facial feature, in the part-to-whole paradigm,
      has been taken as evidence of holistic perception in a large body of face
      perception literature. In this article, we demonstrate that although failure of
      selective attention is a necessary property of holistic perception, its presence
      alone is not sufficient to conclude holistic processing has occurred. One must
      also consider the cognitive properties that are a natural part of information
      processing systems, namely, mental architecture (serial, parallel), a stopping
      rule (self-terminating, exhaustive), and process dependency. We demonstrate that
      an analytic model (nonholistic) based on a parallel mental architecture and a
      self-terminating stopping rule can predict failure of selective attention. The
      new insights in our approach are based on the systems factorial technology, which
      provides a rigorous means of identifying the holistic-analytic distinction. Our
      main goal in the study was to compare potential changes in architecture when 2
      second-order relational facial features are manipulated across different face
      contexts. Supported by simulation data, we suggest that the critical concept for
      modeling holistic perception is the interactive dependency between features. We
      argue that without conducting tests for architecture, stopping rule, and
      dependency, apparent holism could be confounded with analytic perception. This
      research adds to the list of converging operations for distinguishing between
      analytic forms and holistic forms of face perception.

PMID- 20804301
TI  - Long-lasting effects of briefly flashed words and pseudowords in ultrarapid
      serial visual presentation.
AB  - Our ability to identify even complex scenes in rapid serial visual presentation
      (RSVP) is astounding, but memory for such items seems lacking. Rather than
      pictures, we used streams of more than 200 verbal stimuli, rushing by on the
      screen at a rate of more than 12 items per second while participants had to
      detect infrequent names (Experiments 1 and 2) or words written in capitals
      (Experiment 3). By direct and indirect tests, we investigated what is remembered
      of these masses of task-irrelevant distractor words and pseudowords embedded in
      an RSVP stream. Lexical decision, the indirect test applied either immediately
      after each stimulus train or with a delay, revealed strong long-term priming
      effects. Relative to stimuli not shown before, lexical decisions were faster and
      more accurate to words but slower to pseudowords. The size of these effects
      mirrored how often words and pseudowords had occurred in a stream, suggesting
      that memory traces are strengthened with successive presentations and survive for
      several minutes at least. Moreover, in a direct test (old-new categorization),
      words as well as pseudowords benefited from prior occurrence in an RSVP stream if
      they had occurred more than once. These findings parallel recent physiological
      and behavioral evidence for memory consolidation of distractor pictures in RSVP
      and highlight that, despite huge numbers of interfering stimuli, distractor words
      and pseudowords exhibit long-lasting memory effects. Consolidation seems to
      progress at higher cognitive levels at the same time that subsequent stimuli are
      perceptually processed.

PMID- 20804300
TI  - False memories seconds later: the rapid and compelling onset of illusory
      recognition.
AB  - Distortions of long-term memory (LTM) in the converging associates task are
      thought to arise from semantic associative processes and monitoring failures due
      to degraded verbatim and/or contextual memory. Sensory-based coding is
      traditionally considered more prevalent than meaning-based coding in short-term
      memory (STM), whereas the converse is true of LTM, leading to the expectation
      that false memory phenomena should be less robust in a canonical STM task. These
      expectations were violated in 2 experiments in which participants were shown
      lists of 4 semantically related words and were probed immediately following a
      filled 3- to 4-s retention interval or approximately 20 min later in a surprise
      recognition test. Corrected false recognition rates, confidence ratings, and
      Remember/Know judgments reveal similar false memory effects across STM and LTM
      conditions. These results indicate that compelling false memory illusions can be
      rapidly instantiated and that, consistent with unitary models of memory, they
      originate from processes that are not specific to LTM tasks.

PMID- 20804302
TI  - Item-specific encoding produces an additional benefit of directed forgetting:
      evidence from intrusion errors.
AB  - List-method directed forgetting involves encoding 2 lists, between which half of
      the participants are told to forget List 1. When participants are free to study
      however they want, directed forgetting impairs List 1 recall and enhances List 2
      recall in the forget group compared with a control remember group. In a large
      scale experiment, the current work demonstrated that when item-specific encoding
      instructions were enforced during learning, directed forgetting impaired List 1
      recall, but it did not enhance List 2 recall. This pattern was found regardless
      of whether encoding was incidental or intentional. Whenever directed forgetting
      did not enhance List 2 recall, it nevertheless reduced cross-list intrusions.
      These results indicate that directed forgetting can help differentiate memories
      from one another, thereby reducing intrusions from irrelevant competing memories.

PMID- 20804303
TI  - Impact of calcification on diagnostic accuracy of 64-slice spiral computed
      tomography for detecting coronary artery disease: a single center experience.
AB  - BACKGROUND: The main aim of our study was to investigate the influence of
      calcification on the accuracy of 64-slice computed tomography for identification
      of significant coronary artery disease. METHODS: A contrast-enhanced 64-slice
      computed tomography was performed prior to invasive coronary angiography in 168
      consecutive patients with suspected coronary artery disease. All coronary
      segments 1.5 mm or larger in diameter were evaluated for the presence or absence
      of significant coronary artery stenosis, defined as a diameter reduction of >50%.
      The patients were also ranked by total calcium score which was expressed in
      Agatston units and the impacts of calcification on diagnostic accuracy of 64
      slice computed tomography were assessed. Results were compared with quantitative
      coronary angiography as the standard of reference. RESULTS: The overall
      sensitivity, specificity, positive predictive value, and negative predictive
      value of 64-slice computed tomography for detection of significant stenosis were:
      by segments, 95%, 98%, 91%, and 99%, respectively; by patient, 98%, 97%, 96%, and
      99%, respectively; and by artery, 94%, 93%, 91%, and 95%, respectively. In mild
      and moderate calcium scores (0-418 Agatston units), the sensitivity was 100%,
      specificity was 93%, positive predictive value was 97% and negative predictive
      value was 100%. Severe calcification (>419 Agatston units) reduced the
      sensitivity, specificity, positive, and negative predictive values of multi-slice
      computed tomography to 89%, 60%, 89%, and 60%, respectively. CONCLUSION: Our
      study revealed that the 64-slice computed tomography is a highly accurate
      diagnostic modality for detecting hemodynamically significant coronary stenosis;
      however, severe calcification is considered as a shortcoming which limits the
      routine application of multi-slice computed tomography in daily practice.

PMID- 20804304
TI  - Association study of the -866G/A UCP2 gene promoter polymorphism with type 2
      diabetes and obesity in a Tehran population: a case control study.
AB  - BACKGROUND: A functional polymorphism in the uncoupling protein 2 (UCP2) gene
      promoter has been associated with obesity and type 2 diabetes (T2D) in some
      populations. The impact of UCP2 polymorphisms on diabetes and obesity is still
      under debate. Contradictory results have been reported in different populations
      world-wide. To clarify the contribution of the UCP2 gene -866 G/A polymorphism in
      the Iranian population, we studied its association with obesity and T2D. METHODS:
      A total of 225 unrelated subjects were studied: 75 T2D patients without obesity,
      75 obese patients without diabetes and 75 control subjects. The UCP2 -866 G/A
      polymorphism was determined by polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP). RESULTS: In the normal Iranian population, GG
      polymorphism was significantly associated with an increased HDL-C level
      (P=0.027). G/A polymorphism was not associated with obesity and T2D in our study
      population, but the odds ratio (OR) between GG and G/A polymorphism was 0.61 with
      a confidence interval (CI) range of 0.34 - 1.08 in obese patients. Subjects with
      AA genotypes in all of the studied groups showed a lower body mass index (BMI)
      than subjects with the GG genotype. CONCLUSION: Although the data in our study
      population is not statistically significant, the A allele in the UCP2 gene
      promoter seems to be protective against obesity. This may suggest the possibility
      of UCP2 as a target molecule for studies on the etiology and treatment of
      obesity.

PMID- 20804305
TI  - Vitamin deficiency in Golestan Province, northern Iran: a high-risk area for
      esophageal cancer.
AB  - OBJECTIVE: Dietary factors seem to play a major role in esophageal carcinogenesis
      in Golestan Province, a high-incidence area for esophageal cancer in northern
      Iran. The current study was conducted to evaluate previous reports on severe
      deficiency of vitamin intake in Golestan. METHODS: Using a food frequency
      questionnaire, food intake data were collected from 30,463 healthy participants
      in the Golestan Cohort Study. Intake of selected nutrients was compared with
      recommended daily allowance and lowest threshold intake values. RESULTS: Vitamin
      A intake in the majority of participants was lower than recommended values. The
      proportion of participants with intakes lower than lowest threshold intake was as
      follows: urban men, 20%; urban women, 31%; rural men, 48%; and rural women, 64%.
      The pattern of vitamin C deficiency was similar to that of vitamin A, however,
      vitamin C deficiency was less common. Daily intake of vitamin C lower than the
      LTI was as follows: urban men, 6%; urban women, 9%; rural men, 13%; and rural
      women, 19%. On the other hand, protein intake in the majority of the general
      population in Golestan was higher than recommended values. CONCLUSION: Severe
      deficiency in vitamin intake among women and rural dwellers may partly explain
      the high incidence of EC among inhabitants in rural areas and the male:female
      ratio that is approximately 1 in Golestan; while EC is much more common in men in
      many low-incidence areas.

PMID- 20804306
TI  - Psychological and behavioral traits in smokers and their relationship with
      nicotine dependence level.
AB  - BACKGROUND: Although several studies have been performed to evaluate the
      personality differences amongst smokers with different dependency levels, they do
      not use constant criteria for patients selection. The inconsistencies between
      some of these findings suggest the need for using solid criteria such as the
      modified Fagerstrom Tolerance Questionnaire (mFTQ) score to evaluate the relation
      between personality traits and impulsivity differences and the severity of
      nicotine dependency. MATERIALS AND METHODS: In this study, 22 heavily dependent,
      37 lightly dependent and 30 non-smokers were recruited using the mFTQ score, a
      widely used test of nicotine dependence. All participants completed the Beck
      Depression Inventory, Cattle Anxiety Scale, Temperament, and Character Inventory
      and three other personality questionnaires intended to measure impulsivity: the
      Barratt's Impulsiveness Scale, Eysenck Impulsiveness Questionnaire, and
      Zuckerman's Sensation Seeking Scale. Participants also had to perform a
      behavioral choice task, the Delay Discounting Choice, which is designed to assess
      impulsivity. RESULTS: Although heavily dependent smokers scored higher than non
      smokers and lightly dependents on the Beck depression Inventory and most of the
      impulsivity subscales; lightly dependent smokers scored higher than non-smokers
      only on a few subscales of the impulsivity scores. CONCLUSIONS: The mFTQ scores
      correlated significantly with many scores of the impulsivity subscales. These
      results would be helpful to design more specific questionnaires for the
      psychological assessment of smokers according to nicotine dependence level and to
      adopt more etiologic oriented treatment approaches in the future.

PMID- 20804307
TI  - Role of cytochrome P450 2C19 genetic polymorphisms in the therapeutic efficacy of
      omeprazole in Iranian patients with erosive reflux esophagitis.
AB  - BACKGROUND: There are different clinical responses to omeprazole treatment in
      Iranian patients with gastroesophageal reflux disease. Omeprazole is metabolized
      in the liver by the cytochrome p450 2c19 (CYP2C19) enzyme. Two common
      polymorphisms of the CYP2C19 gene affect CYP2C19 enzyme activity. We investigated
      the effect of CYP2C19 gene polymorphisms on the clinical response to treatment
      with omeprazole in Iranian patients with erosive reflux esophagitis. METHODS:
      Eighty-two Iranian patients with reflux esophagitis were enrolled in the study
      and underwent treatment with omeprazole at 40 mg daily for 4 weeks. A 2 mL sample
      of venous blood was obtained from each subject. CYP2C19 genetic polymorphisms
      were detected using the PCR-RFLP method. The patients were grouped into homo
      extensive metabolizers and hetero-extensive metabolizers based on their CYP2C19
      polymorphism. The grade of esophagitis was determined via endoscopy. The symptoms
      score was assessed at the beginning of treatment. RESULTS: Our results showed
      that the rate of complete clinical response to treatment with omeprazole was 95%
      in the hetero-extensive metabolizers group, which was higher than in the homo
      extensive metabolizers group (P<0.001). CONCLUSION: CYP2C19 polymorphism
      influences the therapeutic efficacy of omeprazole in the treatment of Iranian
      patients with erosive reflux esophagitis. The clinical response and endoscopic
      healing of esophagitis are both affected by CYP2C19 genotype condition.

PMID- 20804308
TI  - An outbreak of shigellosis due to Shigella flexneri serotype 3a in a prison in
      Iran.
AB  - BACKGROUND: On June 16 and 17, 2007, the medical clinic of a prison in Isfahan,
      Iran received multiple reports of gastrointestinal illness among prisoners. A
      cross-sectional study was therefore undertaken to determine the extent, causative
      agent and possible source of the outbreak. METHODS: A case-patient was defined
      and patient information was collected with a standardized questionnaire. Stool
      samples were collected from the patients and restaurant employees, and analyzed
      for the presence of enteric bacteria by routine bacteriological methods. Shigella
      isolates were identified and serotyped by commercially available antisera. The
      relationship between the strains was determined using antimicrobial drug
      resistance pattern analysis and enterobacterial repetitive intergenic consensus
      polymerase chain reaction (ERIC-PCR). RESULTS: Seven hundred one inmates
      experienced gastrointestinal illness and severe diarrhea. The attack rate was
      14.02%. Rectal swabs and stool cultures recovered from patients tested positive
      for Shigella flexneri serotype 3a. All tested isolates had a similar antibiotic
      resistance and ERIC-PCR pattern. Our findings demonstrated that raw vegetables
      were more likely to be the causative agent of this outbreak. CONCLUSION: The
      results indicated that a single clone of S. flexneri was responsible for this
      outbreak. Although we could not trace the exact origin of the organism, the
      consumption of raw vegetables one day prior to the onset of illness was strongly
      associated with an increased risk of S. flexneri infection. This study emphasizes
      the need for accurate monitoring and surveillance of food and vegetables consumed
      in prisons.

PMID- 20804309
TI  - Post-transplantation lymphoproliferative disorder after liver transplantation:
      report of 5 cases among more than 550 liver transplants in Iran.
AB  - BACKGROUND: Post-transplantation lymphoproliferative disorders (PTLD) are a
      spectrum of diseases defined as polyclonal or monoclonal proliferations of
      lymphocytes which occur after solid organ transplants. In this study, we report
      our first experiences with PTLD following liver transplantation in Iran. METHODS:
      We retrospectively analyzed five cases of PTLD which followed liver
      transplantation among more than 550 liver transplants in our center. Of these,
      three were pediatric cases and two were adults. The underlying causes were
      tyrosinemia, autoimmune hepatitis, and progressive familial intrahepatic
      cholestasis (PFIC) in the three pediatric cases. HCV hepatitis was the primary
      cause for cirrhosis in one of the adults and the other adult was labeled as
      cryptogenic cirrhosis. All cases, except for one, developed PTLD during the first
      year following liver transplantation. RESULTS: Patients were diagnosed as PTLD, B
      cell, MALT and Hodgkin-like (according to the WHO classification of PTLD). The
      three pediatric patients died despite discontinuation of immunosuppressive drugs
      and chemotherapy. Fortunately both adult patients, until now, are still alive.
      CONCLUSION: The incidence of PTLD in our center is lower than previous reports
      from other centers (0.9%), with a 60% mortality rate and worse prognosis in the
      pediatric age group.

PMID- 20804310
TI  - Effect of timing of umbilical cord clamp on newborns' iron status and its
      relation to delivery type.
AB  - OBJECTIVE: This study was conducted to evaluate the hematological effects of
      umbilical cord clamp timing and delivery type in term infants 48 hours after
      birth in Imam Hossein Hospital, Tehran, Iran. METHOD: From Oct 2007 - March 2008,
      100 mother-infant eligible pairs were selected and divided by cord clamp timing
      (< or =15 s and >15 s) for hematologic value determination between the two
      groups. Data analysis was performed with SPSS for Windows statistical package
      (version 13). RESULTS: Maternal hematological status was assessed upon admission
      to the delivery room. A total of 100 mother-infant pairs were divided into two
      groups: delayed cord clamp time within 15 s (n=70) or early cord clamp time [15 s
      after delivery (n=30)]. The groups had similar demographic and biomedical
      characteristics at baseline. Forty-eight hours after delivery the mean infant
      hemoglobin (Hgb; 16.08 gm/dL vs. 14.5 gm/dL; P<0.001) and hematocrit (Hct 47.6
      vs. 42.8; P<0.001) levels were significantly higher in the delayed clamping
      group. There was no significant difference in ferritin levels (214.7 vs. 173.6
      ng/dL; P=0.08). Fifty infants were born vaginally and 50 were delivered by
      cesarean section. Infants delivered vaginally had significantly more delayed cord
      clamp times (>15 s; P<0.001). CONCLUSION: Delaying cord clamping increases the
      red cell mass in term infants. It is a safe, simple and low cost delivery
      procedure that should be incorporated in integrated programs that are aimed at
      reducing iron deficiency anemia in infants in developing countries. Vaginal
      delivery facilitates this action.

PMID- 20804311
TI  - Appropriate definition of metabolic syndrome among Iranian adults: report of the
      Iranian National Committee of Obesity.

PMID- 20804312
TI  - Mycosis fungoides of the true vocal cord: a case report and review of the
      literature.
AB  - Mycosis fungoides is the most common type of cutaneous malignant T cell lymphoma
      which primarily affects skin. However, extracutaneous manifestation may occur in
      advanced stages, mostly observed in postmortem studies. We present a case of
      mycosis fungoides that disseminated to the true vocal cord of a 48-year-old
      African American man who presented with hoarseness. Only two cases that have also
      demonstrated a rare involvement of the true vocal cord have been reported in the
      English literature. In both cases, mycosis fungoides infiltration of the true
      vocal cord was seen postmortem, along with visceral dissemination of mycosis
      fungoides. We herein describe a single extracutaneous manifestation of mycosis
      fungoides in the true vocal cord of a living patient with a 21-year diagnosis of
      mycosis fungoides. Vocal cord involvement by mycosis fungoides must be considered
      as one of the differential diagnoses in any mycosis fungoides patients who
      complain of persistent hoarseness. Awareness of this entity is clinically
      important due to the necessity of a different management.

PMID- 20804313
TI  - Two rare presentations of fatal anthrax: meningeal and intestinal.
AB  - Anthrax is an ancient disease of animals and men, caused by Bacillus anthracis.
      The diagnosis of cutaneous infection is relatively easy, but other clinical forms
      might escape recognition. We present two rare and fatal forms of anthrax:
      meningeal in a 33-year-old male shepherd and intestinal in a 4-year-old boy. The
      former was admitted to the hospital with complaints of headache, vomiting, fever,
      and decreased level of consciousness. The latter presented with abdominal pain
      and distension, vomiting, and fever. Both cases were proven by animal
      inoculation.

PMID- 20804314
TI  - Combined subcutaneous, intrathoracic and abdominal splenosis.
AB  - We report a case of combined subcutaneous, intrathoracic, and abdominal splenosis
      who presented with attacks of flushing, tachycardia and vague abdominal pain. The
      patient's past medical history included a splenectomy due to abdominal trauma and
      years later, a lung lobectomy due to recurrent pneumonia. An enhancing solid mass
      adjacent to the upper pole of the left kidney and nodular pleural based lesions
      in the left hemi-thorax along with nodular lesions in subcutaneous tissue of the
      left chest wall suggested possible adrenal malignancy with multiple metastases.
      Histopathologic examination demonstrated benign lesions of ectopic splenic
      tissue.

PMID- 20804315
TI  - Ocular leech infestation.
AB  - A 67-year-old myopic man presented to the Ophthalmology Department of a teaching
      hospital in the mountainous state of Sikkim with complaints of red eye, ocular
      discomfort, and sensation of something moving in his right eye that led to
      occasional visual blurring from the previous four days. His symptoms started
      after washing his face in a stream. Clinical diagnosis was a leech in the limbus
      of the right eye at the 12 o'clock position. Ocular leech infestation should be
      considered in a patient with a history of swimming or face washing in streams and
      lakes. Herein we report a case of ocular leech infestation that presented as red
      eye with intermittent blurring of vision in the affected eye, and discuss the
      differential diagnosis and clinical significance.

PMID- 20804316
TI  - Photoclinic. Lepromatous leprosy.

PMID- 20804317
TI  - Photoclinic. Pancreatic neuroendocrine tumor.

PMID- 20804318
TI  - Honoring Avicenna, the great Persian physician on the world's postage stamps.
AB  - Many nations are indebted to Avicenna (Ibn-Sina) for their scientific
      progressions and civilization. Many countries in the Middle East, Africa, and
      Europe have honored Avicenna, the great Persian scientist, by depicting his
      vignette on their postage stamps. The symbolic value of Avicenna has been chosen
      to commemorate scientific occasions, achievements and anniversaries, which
      represents the ultimate performance of conscious honoring.

PMID- 20804319
TI  - Polycyclic aromatic hydrocarbon exposure in oesophageal tissue and risk of
      oesophageal squamous cell carcinoma in north-eastern Iran.

PMID- 20804320
TI  - Obituary: Nosratollah Ameli M.D., FRCS (1913-2010).

PMID- 20804321
TI  - In memoriam: tribute to William W. Meissner. S.J, M.D. 1931-2010.

PMID- 20804322
TI  - Integrating classical and relational psychoanalysis: the therapeutic action of
      analyst's and patient's interacting transferences.

PMID- 20804323
TI  - Discussion of Dr. Michael Varga's paper "Integrating classical and relational
      psychoanalysis".

PMID- 20804324
TI  - E pur si muove.

PMID- 20804326
TI  - Infinite adolescence: a psychoanalytic exploration of tantalizing promises
      inherent to the singularity.

PMID- 20804327
TI  - The Cambridge spies: treason and transformed ego ideals.

PMID- 20804328
TI  - Dreaming and development: early-, mid-, and late-phase shifts in associative and
      interpretive processes.

PMID- 20804329
TI  - From mother tongue to language.

PMID- 20804330
TI  - The impudence of uttering: mother tongue.

PMID- 20804331
TI  - The Aristocrats.

PMID- 20804332
TI  - An overlooked contra-hypothesis?

PMID- 20804335
TI  - Health politics, placental proteins, preeclampsia and pneumothorax.

PMID- 20804336
TI  - Biology of pregnancy-associated plasma protein-A in relation to prenatal
      diagnostics: an overview.
AB  - Pregnancy-associated plasma protein-A (PAPP-A) is highly efficient as a serum
      marker in first-trimester screening for chromosomal abnormalities. Furthermore,
      there is increasing evidence that low levels of PAPP-A in the first trimester are
      associated with adverse pregnancy outcomes such as preterm delivery, intrauterine
      growth retardation, preeclampsia, and stillbirth. PAPP-A is a glycoprotein,
      produced in the placenta, and it is present in the maternal circulation in
      increasing concentrations during pregnancy. By means of its proteolytic activity,
      PAPP-A functions as a regulatory protein in the insulin-like growth factor
      system, known to be important for placental formation and regulation of fetal
      growth. This overview describes aspects of biochemistry, synthesis, and
      biological functions of PAPP-A, with a focus on information of importance to
      clinicians. The clinical applications of PAPP-A are summarized, and new insights
      regarding the analyses of PAPP-A discussed.

PMID- 20804337
TI  - The morbidly adherent placenta: an overview of management options.
AB  - Abstract Morbidly adherent placenta is often associated with severe maternal
      morbidity. An increased incidence over the recent years may be secondary to the
      increased cesarean section rates. Identification of patients with risk factors
      antenatally is essential for the early diagnosis and management. Diagnosis can be
      achieved by ultrasound or MRI in the majority of cases. Management aims to ensure
      a safe delivery of the fetus, alongside measures of prevention or effective
      management of postpartum hemorrhage. When a hysterectomy is performed, a
      multidisciplinary team with surgical expertise and facilities for transfusion and
      further interventions including arterial ligation and interventional radiology
      should be available. The options for conservative treatments offer the potential
      to preserve fertility but further research with prospective evaluation of the
      different approaches is necessary.

PMID- 20804338
TI  - Validity of self-reported birthweight among middle-aged and elderly women in the
      Danish Nurse Cohort Study.
AB  - OBJECTIVE: To investigate the validity of self-reported birthweight among middle
      aged and elderly women and to identify possible determinants of reporting
      accuracy. SETTING AND DESIGN: The Danish Nurse Cohort Study (DNCS), a prospective
      risk factor and hormone therapy study. POPULATION: Participants in the 1999 DNCS.
      METHODS: Self-reported exact and categorical birthweight data from the DNCS was
      compared with data from the Copenhagen School Health Records Register (CSHRR),
      which contains birthweight data. MAIN OUTCOME MEASURES: Accuracy of self-reported
      birthweight expressed as mean difference with limits of agreement, sensitivity,
      specificity, and positive and negative predictive values (PPV and NPV). RESULTS:
      Exact birthweight was available for 441 participants. The correlation coefficient
      was 0.83. The mean difference was -21 g and limits of agreement were -843 to 818
      g. A total of 74% answered correctly within 250 g while 7% were more than 500 g
      in error. Categorical birthweight was available for 925 participants. A total of
      87% reported the correct birthweight. Sensitivity and PPV were high for normal
      birthweight, whereas specificity and NPV were better for high and low birthweight
      (HBW and LBW). Multiple logistic regression analyses showed that HBW, LBW and
      being the daughter of a young mother decreased the accuracy of self-reported
      birthweight. CONCLUSIONS: Self-reported birthweight is a valid measure of actual
      birthweight among middle-aged and elderly women. Due to the lower accuracy of HBW
      and LBW, studies of the association between birthweight and chronic disease may
      underestimate the true effect of these weights.

PMID- 20804339
TI  - Moderate impact of full-term pregnancy on estimated peak oxygen uptake, physical
      activity and perceived health.
AB  - OBJECTIVE: To study the impact of pregnancy on estimated peak oxygen uptake (VO(2
      peak, est.)), physical activity and perceived health. DESIGN: Prospective cohort
      study. SETTING: Maternal health centers. POPULATION: A cohort of pregnant women.
      Methods. Cycle ergometer test and questionnaires in early pregnancy and 5 months
      postpartum. MAIN OUTCOME MEASURES: VO(2 peak, est.), physical activity and
      perceived health. RESULTS: Regular physical activity was reported by a
      successively lower proportion of women as pregnancy advanced but the proportion
      was regained postpartum. Despite this the difference between average absolute
      VO(2 peak, est.) in early pregnancy and postpartum of 2.44 and 2.42 l/minute,
      respectively, was not significant. The adjusted absolute VO(2 peak, est.) in
      early pregnancy successively increased with age to a maximum at 35 years, after
      which it decreased and among women of the same age the time between 8 and 12
      weeks lowered the VO(2 peak, est.) by 0.130 l/minute. With the Short Form 36 (SF
      36) questionnaire in early pregnancy the women scored their mean mental health to
      72.0 and mean physical health to 79.7. At the postpartum appointment these scores
      were higher (p < 0.0001). Absolute and relative VO(2 peak, est.) in early
      pregnancy were positively correlated to the variation of SF-36's mean physical
      health in early pregnancy (p < 0.0001) and postpartum (p < 0.0001). CONCLUSIONS:
      Pregnancy had a moderate influence on physical fitness and perceived health half
      a year postpartum despite less regular physical activity during pregnancy. VO(2
      peak, est.) in early pregnancy was positively correlated to perceived physical
      health.

PMID- 20804340
TI  - Origin of multiple pregnancies in a subfertile population.
AB  - OBJECTIVE: To evaluate the contribution of different subfertility treatments to
      the number of multiple pregnancies in a subfertile population. DESIGN: A
      prospective cohort study between January 2002 and December 2006. SETTING: A
      subfertility clinic in a large regional training hospital in the Netherlands.
      POPULATION: A total of 1,001 continuing pregnancies, of which 63 (6.3%) were
      multiple. METHODS: Of all pregnancies, mode of conception, outcome and type of
      pregnancy (singleton or multiple) were documented. MAIN OUTCOME MEASURES:
      Proportions of continuing and multiple pregnancies caused by the different modes
      of conception. RESULTS: Of all subfertility related continuing pregnancies, 46%
      were conceived spontaneously, 16% were induced by clomiphene citrate (CC), 2.4%
      by follicle stimulating hormone (FSH) and 14% by intra-uterine insemination
      combined with controlled hyperstimulation (IUI/(COH)). In vitro fertilization
      (IVF) and its related techniques resulted in about a fifth of all continuing
      pregnancies (n = 212), but were responsible for more than half (n = 36) of the
      multiple pregnancies. Furthermore, 18% of the multiple pregnancies were induced
      by IUI/(COH), 3% by FSH, 11% by CC, whereas about 11% were conceived
      spontaneously. CONCLUSIONS: IVF and intra-cytoplasmic sperm injection (ICSI) were
      responsible for the majority of the multiple pregnancies in a subfertile
      population. Therefore, twin prevention should be focused on further promoting
      elective single embryo transfer (eSET). Fertility treatment and particular IVF
      should not be started as long as the spontaneous pregnancy prognosis is good.

PMID- 20804341
TI  - Expression of cellular prion protein in the placentas of women with normal and
      preeclamptic pregnancies.
AB  - OBJECTIVE: The aim of our study was to determine the difference of cellular prion
      protein (PrP(C)) expression in the placentas of women with normal and
      preeclamptic pregnancies. DESIGN: Retrospective study using banked placental
      tissue samples. SETTING: University hospital. POPULATION: Twenty women with
      severe preeclampsia (preeclampsia group) and 20 gestational age-matched
      normotensive women (normal group). SAMPLES: Placental tissue from each woman
      collected at the time of cesarean section. METHODS: Quantitative reverse
      transcription polymerase chain reaction (RT-PCR), western blot analysis, and
      immunohistochemical and immunofluorescent staining for mRNA expression,
      quantification and tissue localization of PrP(C) in each placenta. MAIN OUTCOME
      MEASURES: Increased expression of PrP(C) in preeclamptic placenta. RESULTS:
      Compared with the normal group, PrP(C) and its mRNA were highly expressed in
      preeclampsia (each, p < 0.001). In immunohistochemical and immunofluorescent
      staining, PrP(C) was present at the syncytiotrophoblast, cytotrophoblast,
      endothelial cell, stroma, and decidua of all placentas. When the PrP(C)
      immunoreactivity in each tissue was compared, PrP(C) in endothelial cell, stroma,
      and deciduas was weakly expressed, and there was no difference of its expression
      between two groups. But, the intensity of PrP(C) expression in
      syncytiotrophoblast and cytotrophoblast was much higher in preeclampsia than
      normal. CONCLUSIONS: The increased expression of PrP(C) in preeclamptic placenta
      may be a compensatory phenomenon for preeclampsia related conditions.
      Furthermore, this change in preeclamptic placenta may give an explanation for
      placental response to overcome the preeclamptic conditions.

PMID- 20804342
TI  - An association between cytomegalovirus infection and pre-eclampsia: a case
      control study and data synthesis.
AB  - OBJECTIVE: Pre-eclampsia shares several similarities with atherosclerotic heart
      disease. We explored whether, like atherosclerosis, there is a potential link
      between cytomegalovirus (CMV) infection and pre-eclampsia. DESIGN: CMV IgG, IgM
      and IgA antibodies were determined by enzyme-linked immunosorbent assays in
      serums from pre-eclampsia (n = 78), normotensive intrauterine growth restriction
      (nIUGR) (n = 30) and normal pregnancy controls (n = 109). Data were analyzed by
      chi-squared, Kruskal-Wallis ANOVA and Mann-Whitney U-tests. Further, we conducted
      a comprehensive review of published studies on the relation between CMV infection
      and pre-eclampsia. Risk ratios (RRs) and 95% confidence interval (CI), according
      to CMV infection status, were calculated using Review Manager. MAIN OUTCOME
      MEASURES: Women with pre-eclampsia had increased CMV IgG seropositivity compared
      with nIUGR (p < 0.01) and normal pregnancy controls (p < 0.01). In addition, CMV
      IgG antibody level was higher in pre-eclampsia than normal pregnancy controls (p
      < 0.001). No difference was observed in CMV IgM or IgA among study groups. Data
      synthesis revealed that women with CMV infection were at higher risk in the
      development of pre-eclampsia, compared with women without CMV infection. Combined
      results for six studies yielded a RR of 1.5 (95% CI 1.2-1.9). CONCLUSION: CMV
      infection seems to affect the occurrence of pre-eclampsia. Evaluation of the
      relation between CMV infection and pre-eclampsia may provide mechanistic insights
      into pre-eclampsia-related inflammation.

PMID- 20804343
TI  - National perinatal audit, a feasible initiative for the Netherlands!? A
      validation study.
AB  - OBJECTIVE: To explore the feasibility of a national perinatal audit organization.
      DESIGN: Validation study. SETTING: Three regions in the Netherlands. POPULATION:
      228 cases of perinatal mortality. METHODS: Narratives of perinatal mortality
      cases were assessed by a panel of representatives of all perinatal care provider
      groups. 123 cases were assessed twice. Consensus was defined as 75% agreement.
      For the chance corrected agreement Cohen's kappa statistic was used. MAIN OUTCOME
      MEASURES: Consensus and the chance corrected agreement on three cause of death
      classifications. The presence or absence of substandard factors (SSF) with the
      care provider, the organization of care and the relation of the SSF with
      perinatal death. RESULTS: Consensus rates and chance corrected agreement for
      three cause of death classifications ranged from 92 to 96% and kappa 0.87 to
      kappa 0.93 (very good agreement), with comparable confidence intervals and
      similar values in the validation subset of 123 cases. On the presence of SSF at
      the level of the care provider consensus and chance corrected agreement was 68%
      and kappa 0.53 (moderate), with comparable values in the subset of 123 cases.
      Consensus for the relation between SSF at the level of the care provider and
      perinatal death was 81.4% and kappa 0.68 (good). CONCLUSION: Perinatal audit on a
      national level with relatively large audit groups with many different care
      providers is feasible.

PMID- 20804344
TI  - Perinatal variables and neonatal outcomes in severely growth restricted preterm
      fetuses.
AB  - OBJECTIVE: To investigate the impact of severe preterm intrauterine growth
      restriction on perinatal and neonatal outcomes. DESIGN: Retrospective cohort
      study. SETTING: Tertiary referral fetal medicine unit in London. POPULATION: A
      total of 60 pregnancies affected by early onset severe intrauterine growth
      restriction with fetal abdominal circumference below the third centile and
      abnormal arterial or venous Dopplers between October 2003 and October 2007, and
      control cohort of 77 appropriate-for-gestational age preterm neonates. METHODS:
      Cases were identified from the departmental databases. The neonatal outcomes in
      44 growth restricted survivors were compared with 77 gestation matched
      appropriate-for-gestational age preterm neonates. MAIN OUTCOME MEASURES: Neonatal
      morbidity and neonatal mortality. RESULTS: Of the 60 pregnancies affected by
      severe intrauterine growth restriction, seven were terminated, nine resulted in
      stillbirth and 44 resulted in live births. The growth restricted neonates had
      increased odds of developing respiratory distress compromise (odds ratio (OR)
      2.5, 95% confidence interval (CI) 1.1-6.2) and thrombocytopenia (OR 9.4, 95%CI
      2.9-30.8) in comparison to average-for-gestational age cohorts. We also noted an
      increased risk of neonatal sepsis (OR 2.5, 95%CI 1.1-6.0) and necrotising
      enterocolitis (OR 9.7, 95%CI 1.1-86.0). Sepsis was the major contributing factor
      towards neonatal mortality in the growth restricted cohorts. CONCLUSION: Despite
      intensive fetal surveillance and tertiary level neonatal care, the survival for
      growth restricted fetuses before 28 weeks gestation remains poor with neonatal
      outcome predominantly affected by respiratory morbidity, sepsis and metabolic
      compromise.

PMID- 20804345
TI  - Effect of high parity on the occurrence of prediabetes: a cohort study.
AB  - OBJECTIVE: To assess the effect of parity on the occurrence of prediabetes
      defined as an abnormal fasting plasma glucose (5.6-6.9 mmol/l), an abnormal 2
      hour oral glucose tolerance test (7.7-11.1 mmol/l), or both, before 12 weeks
      gestation or at least 6 weeks after delivery. DESIGN: Retrospective cohort study.
      SETTING: Nested on a community trial Delaying the Development of Diabetes
      Mellitus type 2 (AMAL study) in Oman. POPULATION: 532 women with a total of 3,196
      pregnancies. METHODS: We conducted sets of Cox proportional hazard regression
      analyses: crude, age-adjusted and full models which adjusted for maternal age,
      education, family income and year of delivery. MAIN OUTCOME MEASURES: Hazard
      ratio (HR) of the effect of parity on prediabetes. RESULTS: We enumerated 258
      cases of prediabetes over 8,529 person-years of follow up. In the crude model,
      high parity (> or =5) pregnancies carried a higher risk of prediabetes than low
      parity (<5) pregnancies (HR = 3.72; 95% CI = 2.80, 4.91), and the prediabetes
      incidence rate increased in a dose-response fashion over multiple categories of
      parity. In age-only models, the association attenuated with control of the
      confounding effect of maternal age (HR = 1.05; 95% CI = 0.76, 1.45). Adjusting
      for other confounders in the full models yielded similar results to those
      adjusted for maternal age only. CONCLUSIONS: The apparent effect of parity on the
      occurrence of prediabetes is attributable to the confounding effect of maternal
      age rather than to high parity.

PMID- 20804346
TI  - Clinical findings, pain descriptions and physical complaints reported by women
      with post-natal pregnancy-related pelvic girdle pain.
AB  - The objective was to describe clinical findings and pain patterns following the
      provocation by activities of daily living (ADL) in women suffering from pregnancy
      related post-natal pelvic pain 6-12 months after delivery. Forty-one informants
      answered questionnaires regarding pain characteristics in respect to 14 different
      ADL. All informants had bilateral pain, and typically it was described as an
      aching pain in the areas of the posterior superior iliac spines and in the
      symphyseal region. Running was the most provocative activity, followed by
      domestic work and by activities involving pushing and pulling. Duration of the
      activity had a great impact on the tolerance for all activities, and for the
      majority of the women, menstruation and ovulation caused an exacerbation of the
      symptoms.

PMID- 20804347
TI  - Evaluation of the introduction of a new treatment for the termination of
      pregnancy in The Netherlands.
AB  - All hospital-based gynecologists in The Netherlands were sent a questionnaire on
      the termination of pregnancy with off-label drugs in the absence of treatment
      protocols. Response was received from 93.2% of the teaching hospitals and 87.9%
      of the non-teaching hospitals, thus representing practice of nearly all
      gynecologists working in The Netherlands. More than 40 different regimens were
      used for five different indications. Gynecologists embarked on a large number of
      different regimens of which a distressing number do not have any merits to be
      found in studies or guidelines illustrating that, without clear protocols or
      guidelines, the implementation of new medical treatments is potential haphazard
      and based on personal preference. Suboptimal treatment regimens will frustrate
      patients and doctors and deprive future patients from the most efficacious and
      patient friendly treatment regimes available.

PMID- 20804348
TI  - Plasma levels of apolipoprotein M in normal and complicated pregnancy.
AB  - Apolipoprotein M (apoM) is mainly associated with high-density lipoprotein in
      human plasma. Despite several studies suggesting apoM as an anti-atherogenic, its
      function is not yet fully understood. Plasma apoM was measured in normal
      pregnancies at four different gestational ages and in the postpartum period to
      investigate whether the concentration of apoM changes during pregnancy. In
      addition, apoM was measured at 13 weeks in women who subsequently developed
      preeclampsia, gestational diabetes, recurrent miscarriage, or small-for
      gestational age babies, and in women with uncomplicated pregnancies. The plasma
      concentrations of apoM increased during pregnancy to reach highest levels in the
      postpartum period. Thus, plasma apoM in non-pregnant women was around 0.77
      micromol/l, 0.88 micromol/l at 40 gestational weeks, and 1.05 micromol/l in the
      postpartum period (p < 0.0001). No differences in plasma concentrations of apoM
      were found among the studied pregnancy complications.

PMID- 20804349
TI  - Conservative approach in heavy postpartum hemorrhage associated with
      coagulopathy.
AB  - The application of external uterine elastic bandage is a new approach to control
      serious postpartum hemorrhage. This was applied in 10 consecutive patients with
      severe postpartum hemorrhage. After circulatory stabilization by external aortic
      compression, laparotomy and identification of the source of bleeding, compression
      sutures were applied and intrauterine fibrin glue was administered. Immediately
      thereafter, external uterine elastic bandage was wrapped around the uterus to
      compress it and stop the bleeding. After hemostasis had persisted for some time,
      the bandage was removed, and uterus and abdomen were then closed. Application of
      external uterine elastic bandage resulted in hemostasis within 45 minutes after
      aortic compression. Hysteroscopy 6 months after the procedure showed no signs of
      uterine ischemia or endometrial adhesions. In conclusion, external elastic
      uterine bandage is a simple tool that seems to improve hemostasis and prevent
      hysterectomy in heavy postpartum hemorrhage.

PMID- 20804350
TI  - Morbidity associated with failed vaginal birth after cesarean section.
AB  - We investigated morbidity and factors associated with failed vaginal birth after
      cesarean delivery (VBAC). In a retrospective cohort study maternal and neonatal
      outcomes of women who underwent VBAC in three Nigerian University Teaching
      Hospitals were reviewed. Univariate, followed by multivariate analyses, were
      conducted. VBAC was successful in 683 of 1,013 women (67.4%), whereas 330 (32.6%)
      had failed VBAC. Failed VBAC was associated with higher incidence of
      chorioamnionitis, postpartum hemorrhage, blood transfusion, uterine rupture,
      hysterectomy, and composite major neonatal morbidities. Younger age, lack of
      previous vaginal delivery, induction of labor and fetal weight >4,000 g were risk
      factors for failed VBAC. A majority of women who try VBAC achieve a vaginal
      delivery. Failed VBAC is associated with increased maternal and neonatal
      morbidity and is somewhat predictable.

PMID- 20804351
TI  - Continuous glucose monitoring-enabled insulin-pump therapy in diabetic pregnancy.
AB  - We describe the feasibility of continuous glucose monitoring (CGM)-enabled
      insulin-pump therapy during pregnancy in a woman with type 1 diabetes, who was
      treated with CGM-enabled insulin-pump therapy in her third pregnancy. During her
      first pregnancy, the woman was treated with multiple daily injections and
      baseline HbA1c was 8.9%. Due to pre-eclampsia, the child was born preterm, and
      had neonatal hypoglycemia. In the planning of the second pregnancy, insulin-pump
      therapy was initiated, resulting in an HbA1c of 6.8% in early pregnancy. Due to
      pre-eclampsia, the second child was born preterm, but without neonatal morbidity.
      Before her third pregnancy, CGM-enabled insulin-pump therapy was introduced, and
      HbA1c was 6.4% in early pregnancy. The patient was satisfied with this therapy,
      pre-eclampsia did not occur, and the child was born at term without neonatal
      morbidity. CGM-enabled insulin-pump therapy appears feasible in diabetic
      pregnancies.

PMID- 20804353
TI  - An example of a less medicalized approach to the management of late miscarriage
      of the first twin.

PMID- 20804355
TI  - An unexpected outcome of blunt ocular trauma: rupture of three muscles.
AB  - INTRODUCTION: Traumatic strabismus due to isolated extraocular muscle rupture is
      uncommon. Treatment usually depends on the severity of both the subjective and
      objective findings. METHODS: We report a male patient with restricted abduction
      and supraduction in the right eye follow ing a blunt ocular trauma. The
      exploration revealed the rupture of superior rectus, superior oblique, and
      lateral rectus muscles. Only lateral rectus muscle could be sutured to the
      proximal segment. Superior rectus and superior oblique muscles were severed
      brutally, so that repairing was not possible. RESULTS: On the day after
      exploration and primary suturation, there was 25 prism diopters (PD) hypotropia
      and 15 PD esotropia in his right eye with severe limited supraduction and
      abduction. His major complaint was a large vertical diplopia which resolved
      partially with the prismatic glasses prescribed. After 6 months follow-up, medial
      rectus and inferior rectus recession was performed in the right eye. The patient
      had a limited but improved abduction after the operation. He was orthotropic and
      had a single binocular vision in the primary position. DISCUSSION: In suspected
      extraocular muscle ruptures, orbital imaging methods and surgical exploration
      should be considered promptly. MRI may be mandatory to demonstrate the severed
      muscles in cases with persistent diplopia and normal CT. Prognosis is usually
      better in patients having partial extraocular muscle damage and treatment options
      should be evaluated on patient basis.

PMID- 20804356
TI  - A unique use for a corneal tattoo.
AB  - INTRODUCTION: Corneal tattoos have been previously used in managing corneal
      pathologies. METHODS: We describe a case of a 28-year-old male who presented with
      intractable binocular diplopia, which was relieved with a corneal tattoo.
      CONCLUSION: This is a novel application of corneal tattooing for the alleviation
      of intractable binocular diplopia.

PMID- 20804357
TI  - Awareness of exodeviation in children with intermittent exotropia.
AB  - PURPOSE: To describe how children with intermittent exotropia (IXT) are aware of
      their exodeviation. METHODS: Twenty-four children with IXT, aged 5 to 17 years,
      median 10.5 years, were recruited. Individual interviews with the children were
      audiotaped and transcribed. Interviews were based on 10 open-ended questions and
      discussion was encouraged. Transcripts were reviewed to identify phrases
      describing the child's awareness of the exodeviation as distinct from phrases
      describing the way intermittent exotropia affects their quality of life. Phrases
      were reviewed to identify specific topic areas and the type and frequency of
      topics were analyzed. RESULTS: Nineteen (79%) of 24 children expressed awareness
      of the exodeviation. One hundred twenty phrases were extracted and 18 topic areas
      identified. The most frequently mentioned topics were comments from others (15
      [63%] of 24), general awareness of deviation (10 [42%] of 24), ocular sensation
      (10 [42%] of 24), and correction of exodeviation by blinking (7 [29%] of 24).
      CONCLUSIONS: In our study, most patients with IXT were aware of their eye
      condition, but patient experience varied. In individual interviews, children
      described awareness of their eye condition mainly due to comments from others.
      Awareness of ability to correct the exodeviation by blinking was common and may
      be related to mechanisms used to control IXT.

PMID- 20804358
TI  - The method of treatment cessation and recurrence rate of amblyopia.
AB  - BACKGROUND AND PURPOSE: To date, much of the research regarding amblyopia has
      been focused on which therapeutic modality is the most efficacious in amblyopia
      management. Unfortunately, there is a lack of research into which method of
      treatment cessation is the most appropriate once therapy has been completed. The
      purpose of this study is to investigate if the cessation method affects the
      recurrence rate of amblyopia. METHODS: This study was a prospective randomized
      clinical trial of 20 subjects who were wearing full-time occlusion and were at
      the end point of their therapy. The subjects were randomized into one of two
      groups: abrupt cessation or therapy tapering. All subjects were followed for 3
      consecutive 4-week intervals, for a total of 12 weeks, to assess the short-term
      recurrence rate of amblyopia. Subjects who were in the tapered group had their
      occlusion reduced from full-time occlusion (all waking hours minus one) to 50% of
      waking hours at study enrollment (i.e., from 12 hours/day to 6 hours per day);
      occlusion was reduced by an additional 50% at the first 4-week study visit (i.e.,
      from 6 hours/day to 3 hours), with occlusion being discontinued completely at the
      week 8 visit. All subjects who were in the abrupt cessation group had their full
      time occlusion discontinued completely at the start of the study (i.e., from 12
      hours/day to none). Additional assessments were also conducted at week 26 and
      week 52 post-therapy cessation to determine the longer term amblyopia regression
      rate. For the purposes of this study, recurrence was defined as a 0.2 (10
      letters) or more logarithm of the minimum angle of resolution (logMAR) loss of
      visual acuity. RESULTS: A recurrence of amblyopia occurred in 4 of 17 (24%; CI 9%
      47%) participants completing the study by the week 52 study end point. There were
      2 subjects from each treatment group who demonstrated a study protocol-defined
      recurrence. CONCLUSION: There was a 24% risk of amblyopia recurrence if therapy
      was discontinued abruptly or tapered in 8 weeks. In this small sample, the
      assigned cessation method did not affect the rate of amblyopia recurrence. It is
      recognized that the smaller sample size in our study prevents us from making
      definitive conclusions on the potential role that abrupt cessation has on the
      regression rate of amblyopia. The sample size was too small to reach an
      acceptable level of statistical power; therefore the generalizability of the
      findings to the broad population of all patients with amblyopia requires
      continuing research. This study therefore could be considered as a pilot study.

PMID- 20804360
TI  - Prof. Dr. C. H. Sattler University Eye Clinic, Breslau Head: Prof. Dr. A.
      Bielschowsky. Experiences with the elimination of amblyopia and the restoration
      of binocular vision in squinters, Part II. 1927.

PMID- 20804359
TI  - Predictability of strabismus surgery in children with developmental disorders
      and/or psychomotor retardation.
AB  - BACKGROUND: Children with developmental disorders and/or psychomotor delay may
      respond differently to strabismus surgery than children who develop normally, but
      the literature is conflicting. METHODS: We studied 37 patients with spasm,
      trisomy 21, prematurity, epilepsy, psychomotor retardation, and/or hydrocephalus
      (study group) and 67 control patients, all between 14 months and 14 years of age.
      All received a recession of one or both medial rectus muscles (Rc-surgery) or a
      monocular recession-resection of medial-lateral rectus muscles (RcRs-surgery) for
      esotropia. Rc-surgery was performed in cases with convergence excess. Spectacles
      were prescribed prior to surgery for all hyperopia > 2D, all partly accommodative
      esotropia, and all myopia. RESULTS: (effect per mm of surgery): For Rc-surgery,
      after 2 months follow-up, at 2.5 m fixation distance, the effects (change of
      angle per millimeter of surgery, mean + or - SD) were 2.07 + or - 0.82 degrees
      /mm (study group) and 1.07 + or - 0.74 degrees /mm (control group) (P < 0.001).
      At 30 cm fixation distance, the effects were 2.42 + or - 0.79 degrees /mm (study
      group) and 1.53 + or - 1.00 degrees /mm (control group) (P < 0.001). Effects at
      infinity were similar to those at 2.5 m. Because of this larger effect on near
      angles, convergence excess decreased after surgery in both study and control
      groups. For RcRs-surgery, at 2.5 m fixation distance, the effects were 1.78 + or 
      0.43 degrees /mm (study group) and 1.78 + or - 0.42 degrees /mm (control group)
      (P = 0.741). At 30 cm fixation distance, the effects were 1.82 + or - 0.39
      degrees /mm (study group) and 1.84 + or - 0.58 degrees /mm (control group) (P =
      0.918). At fixation distance infinity, results were similar to those at 2.5 m.
      For both Rc-surgery and RcRs-surgery, reported differences were similar after one
      year follow-up. Success of surgery: After 2 months of follow-up, esotropia
      between 0-6 degrees was present, for Rc-surgery in 64% in the study group (with
      adjusted dosages) and 93% in the control group; and for RcRs-surgery in 66% in
      the study group and 88% in the control group. CONCLUSIONS: Rc-surgery in children
      with developmental disorders and/or psychomotor delay has a larger effect per mm
      of surgery than in normal children. RcRs-surgery has a similar effect in delayed
      and normal children.

PMID- 20804362
TI  - The J-curve phenomenon revisited.

PMID- 20804363
TI  - Comment on a letter to the editor: Is the pneumoretroperitoneum really developed
      after acupuncture?

PMID- 20804364
TI  - Use of Chinese Medicine among patients with liver cancer in Taiwan.

PMID- 20804365
TI  - D-ribose aids fatigue in aging adults.

PMID- 20804366
TI  - Randomized controlled trial of acupuncture versus sham acupuncture in autism
      spectrum disorder.
AB  - OBJECTIVE: We aim to study the efficacy of acupuncture versus sham acupuncture in
      children with autism spectrum disorder. METHODS: A single-blind randomized
      control trial was conducted in 50 children. These children were randomly assigned
      to the treatment group with tongue acupuncture (40 sessions over 8 weeks) or the
      control group (sham tongue acupuncture to nonacupoints in the tongue). RESULTS:
      There was improvement in both the treatment and control groups in all assessed
      measures but more so in the treatment than in the control group: (1) eye-hand
      coordination, performance, and practical reasoning of Griffiths Mental
      Developmental Scale; (2) sensory-motor, social, affectual, language, and total
      score of Ritvo-Freeman Real Life Scale; (3) Comprehension Language age in the
      Reynell Language Developmental Scale; and (4) Total Score and Mental Age in
      Symbolic Play Test. The only statistically significant improvement in the
      treatment as compared to the control group was seen in self-care and cognition
      domains of the Functional Independence Measure for children. CONCLUSIONS: We had
      demonstrated that a short course of acupuncture had efficacy in improving various
      developmental and behavioral aspects of children with autism. The long-term
      efficacy in functional gain needs to be further explored.

PMID- 20804367
TI  - Pilot study of the effect of methyl B12 treatment on behavioral and biomarker
      measures in children with autism.
AB  - OBJECTIVES: The study objectives were to determine whether methyl B12 treatment
      improves behavioral measures in children with autism and whether improvement is
      associated with increased plasma concentrations of glutathione (GSH) and an
      increased redox ratio of reduced glutathione to oxidized glutathione (GSH/GSSG),
      both of which have been previously identified to be low in children with autism.
      DESIGN: This was a 12-week, double-blind, placebo-controlled, cross-over clinical
      trial of injectable methyl B12. Following this 12-week study, subjects were given
      the option of entering a 6-month open-label trial of methyl B12.
      SETTINGS/LOCATION: All procedures took place at the UC Davis M.I.N.D. Institute.
      SUBJECTS: Subjects were 3 to 8 years old with autism. INTERVENTIONS: All subjects
      received 6 weeks of placebo and 6 weeks of methyl B12 at a dose of 64.5 mcg/kg
      every three days administered subcutaneously into the buttocks. OUTCOME MEASURES:
      Blood for GSH analysis and behavioral assessments were obtained at baseline, week
      6, and week 12. RESULTS: Thirty (30) subjects completed the 12-week, double-blind
      study and 22 subjects completed the 6-month extension study. No statistically
      significant mean differences in behavior tests or in glutathione status were
      identified between active and placebo groups. Nine (9) subjects (30%)
      demonstrated clinically significant improvement on the Clinical Global Impression
      Scale and at least two additional behavioral measures. More notably, these
      responders exhibited significantly increased plasma concentrations of GSH and
      GSH/GSSG. CONCLUSIONS: Comparison of the overall means between groups suggests
      that methyl B12 is ineffective in treating behavioral symptoms of autism.
      However, detailed data analysis suggests that methyl B12 may alleviate symptoms
      of autism in a subgroup of children, possibly by reducing oxidative stress. An
      increase in glutathione redox status (GSH/GSSG) may provide a biomarker for
      treatment response to methyl B12. Additional research is needed to delineate a
      subgroup of potential responders and ascertain a biomarker for response to methyl
      B12.

PMID- 20804368
TI  - Effect of Cs-4 (Cordyceps sinensis) on exercise performance in healthy older
      subjects: a double-blind, placebo-controlled trial.
AB  - OBJECTIVE: The objective of this study was to examine the effect of Cs-4
      (Cordyceps sinensis) on exercise performance in healthy elderly subjects. DESIGN:
      Twenty (20) healthy elderly (age 50-75 years) subjects were enrolled in this
      double-blind, placebo-controlled, prospective trial. The subjects were taking
      either Cs-4 333 mg or placebo capsules 3 times a day for 12 weeks. MEASUREMENT:
      Subjects received baseline screening including physical examination and
      laboratory tests. Maximal incremental exercise testing was performed on a
      stationary cycle ergometer using breath-by-breath analysis at baseline and at the
      completion of the study. RESULTS: After receiving Cs-4 for 12 weeks, the
      metabolic threshold (above which lactate accumulates) increased by 10.5% from
      0.83 +/- 0.06 to 0.93 +/- 0.08 L/min (p < 0.02) and the ventilatory threshold
      (above which unbuffered H(+) stimulates ventilation) increased by 8.5% from 1.25
      +/- 0.11 to 1.36 +/- 0.15 L/min. Significant changes in metabolic or ventilatory
      threshold were not seen for the subjects in the placebo group after 12 weeks, and
      there were no changes in Vo(2) max in either group. CONCLUSION: This pilot study
      suggests that supplementation with Cs-4 (Cordyceps sinensis) improves exercise
      performance and might contribute to wellness in healthy older subjects.

PMID- 20804369
TI  - Review of economic methods used in complementary medicine.
AB  - OBJECTIVE: The purpose of this research is to review the economic methods used in
      complementary medicine (CM). METHOD: A comprehensive literature review was
      undertaken (1995-2007) to identify peer-reviewed articles related to economic
      methods used in CM. RESULTS: The literature found 15 full economic evaluations of
      CM: 3 in the manipulative and body-based practices, 5 in the whole medical
      systems, and 7 in the biologically based practices. No evaluations were
      identified for the areas of mind-body medicine, alternative medical systems, or
      energy medicine. The review failed to locate any articles that used alternate
      economic methods such as contingent valuation or discrete choice modelling. The
      overall consensus from the 15 economic evaluations, despite variations in project
      design and methodological rigor, was that CM, as evaluated in these studies, was
      cost-effective compared to usual care. CONCLUSIONS: As health care costs continue
      to rise, decision makers, both consumers and policymakers, must allocate scarce
      resources toward those treatments that offer the best value for the money.
      Considerable scope exists to advance the science behind CM through a more
      systematic integration of economic methods into CM research.

PMID- 20804370
TI  - Brain activation during compassion meditation: a case study.
AB  - OBJECTIVES: B.L. is a Tibetan Buddhist with many years of compassion meditation
      practice. During meditation B.L. uses a technique to generate a feeling of love
      and compassion while reciting a mantra. The aim of the present study was to
      investigate the neural correlates of compassion meditation in 1 experienced
      meditator. METHODS: B.L. was examined by functional magnetic resonance imaging
      during compassion meditation, applying a paradigm with meditation and word
      repetition blocks. RESULTS: The most significant finding was the activation in
      the left medial prefrontal cortex extending to the anterior cingulate gyrus.
      Other significant loci of activation were observed in the right caudate body
      extending to the right insula and in the left midbrain close to the hypothalamus.
      CONCLUSIONS: The results in this study are in concordance with the hypothesis
      that compassion meditation is accompanied by activation in brain areas involved
      with empathy as well as with happy and pleasant feelings (i.e., the left medial
      prefrontal cortex and the anterior cingulate gyrus).

PMID- 20804371
TI  - Association between single-nucleotide polymorphisms in Mal/TIRAP and interleukin
      10 genes and susceptibility to invasive haemophilus influenzae serotype b
      infection in immunized children.
AB  - BACKGROUND: The development of invasive Haemophilus influenzae serotype b (Hib)
      disease after prior immunization with the Hib conjugate vaccine (ie, Hib vaccine
      failure) is extremely rare, suggesting that affected children may have an
      underlying genetic susceptibility in their immune response. The objective of this
      study was to investigate single-nucleotide polymorphisms (SNPs) known to affect
      function in biologically plausible genes in relation to the risk of Hib vaccine
      failure and its clinical manifestations. METHODS: The families of UK children
      with Hib vaccine failure diagnosed during the period October 1992 through
      December 2005 were identified through enhanced national surveillance and
      approached for the study at a median interval of 4 years after invasive disease.
      The Wellcome Trust Case Control Consortium data sets were used as controls.
      Nineteen functional SNPs in 14 immune response genes were investigated in 172
      white children. RESULTS: The recessive homozygous genotype for a SNP in the TIRAP
      (also known as MAL) gene (rs1893352) that is in strong linkage disequilibrium
      (r2=0.93) with the known functional Ser180Leu polymorphism in white persons was
      strongly associated with nonmeningitis cases of Hib vaccine failure (odds ratio,
      5.6; 95% confidence interval, 2.7-11.5; P=1.2 x 10(-7)). In addition, the
      recessive homozygous genotype for another SNP (rs1554286) in strong linkage
      disequilibrium with both the C-819T (r2=0.87) and C-592A (r2=0.75) promoter
      polymorphisms in the interleukin-10 gene was associated with epiglottitis only
      (odds ratio, 5.8; 95% confidence interval, 2.4-14.2; P=1.1 x 10(-5)).
      CONCLUSIONS: Our findings strongly suggest that the development of invasive Hib
      disease after prior immunization is in part genetically determined and may direct
      the immune response to specific clinical manifestations.

PMID- 20804372
TI  - Prediction of response to pegylated interferon plus ribavirin by IL28B gene
      variation in patients coinfected with HIV and hepatitis C virus.
AB  - BACKGROUND: Variation in the IL28B gene is associated with sustained virologic
      response (SVR) to pegylated interferon plus ribavirin in hepatitis C virus (HCV)
      monoinfected patients with genotype 1. Data on other genotypes and on patients
      coinfected with human immunodeficiency virus (HIV) and HCV are more limited. We
      aimed to assess the predictive ability of variations in the single-nucleotide
      polymorphism rs12979860 for SVR in HIV/HCV-coinfected patients, regardless of HCV
      genotype. METHODS: The rs12979860 genotype was determined by polymerase chain
      reaction in 154 patients who had received therapy against HCV with pegylated
      interferon plus ribavirin. RESULTS: rs12979860 genotype was TT in 20 patients
      (13%), TC in 66 patients (43%), and CC in 68 patients (44%). Rates of SVR in
      patients with genotype CC and in those with genotype TC or TT, according to HCV
      genotype, were, respectively, 50% and 17% (P < .001) in patients with genotype 1,
      80% and 25% (P = .027) in patients with genotype 4, and 93% and 77% (P = .115) in
      patients with genotype 3. The median (interquartile range) low-density
      lipoprotein cholesterol level in patients with rs12979860 CC was 89 mg/dL (73-120
      mg/dL) versus 75 mg/dL (55-91 mg/dL) (P = .001) in those with TC or TT.
      Independent predictors of SVR were HCV genotype 2-3 (odds ratio [OR], 13.98; 95%
      confidence interval [CI], 4.87-40.1; P < .001), rs12979860 CC (OR, 5.05; 95% CI,
      2.04-12.5; P < .001), baseline plasma HCV RNA load of < or =600,000 IU/mL (OR,
      1.99; 95% CI, 1.18- 3.34; P = .009), and female sex (OR, 4.28; 95% CI, 1.08
      16.96; P = .039). CONCLUSIONS: IL28B gene variations independently predict SVR in
      HIV/HCV-coinfected patients with HCV genotype 1 and non-genotype 1 HCV infection.
      The association between rs12979860 and plasma low-density lipoprotein cholesterol
      suggests that the system low-density lipoprotein ligand/receptor might be
      involved in the effect of this genotype.

PMID- 20804373
TI  - Results of a national survey of infectious diseases specialists regarding
      influenza vaccination programs for healthcare workers.
AB  - A minority of infectious diseases consultants currently work in healthcare
      institutions requiring influenza vaccination for healthcare workers, and in
      approximately half of these institutions, the healthcare workers who refuse
      vaccination do not face substantial consequences for their refusal. Although true
      mandatory policies are not common, a majority of infectious diseases consultants
      support such policies.

PMID- 20804374
TI  - Epidemiology of H1N1 (2009) influenza among healthcare workers in a tertiary care
      center in Saudi Arabia: a 6-month surveillance study.
AB  - BACKGROUND: Certain emerging infections, such as severe acute respiratory
      syndrome and avian influenza, represent a great risk to healthcare workers
      (HCWs). There are few data about the epidemiology of H1N1 influenza among HCWs.
      METHODS: We conducted a prospective surveillance study for all HCWs at King
      Abdulaziz Medical City (Riyadh, Saudi Arabia) who were confirmed positive for
      H1N1 influenza by polymerase chain reaction (PCR) from June 1 through November
      30, 2009. RESULTS: During 6 months of surveillance, 526 HCWs were confirmed
      positive for H1N1 influenza. The distribution of these cases showed 2 clear
      outbreaks: an initial outbreak (peak at early August) and a shorter second wave
      (peak at end of October). Among all PCR-confirmed cases, the attack rate was
      significantly higher in clinical HCWs than in nonclinical HCWs (6.0% vs 4.3%; P <
      .001) and in HCWs in emergency departments than in HCWs in other hospital
      locations (17.4% vs 5.0%, P < .001). The percentage of HCWs who received regular
      influenza vaccination was greater for clinical HCWs than for nonclinical HCWs
      (46.2% vs 24.6%; P < .001). The majority of HCWs with confirmed H1N1 influenza
      were young (mean age + or - standard deviation, 34.5 + or - 9.5 years), not Saudi
      (58.4%), female (55.1%), and nurses (36.1%). Approximately 4% of women who were
      less than 50 years old were pregnant. Reported exposures included contact with a
      case (41.0%), contact with a sick household member (23.8%), and recent travel
      history (13.3%). Respiratory symptoms (98.0%), including cough (90.1%), were the
      most frequently reported symptoms, followed by muscle aches (66.2%), fever
      (62.5%), headache (57.9%), diarrhea (16.5%), and vomiting (9.8%). None of these
      HCWs died, and all recovered fully without hospital admission. CONCLUSIONS: The
      results confirm the vulnerability of HCWs, whether clinical or nonclinical, to
      emerging H1N1 influenza.

PMID- 20804375
TI  - Seroprevalence of measles antibodies among high-risk healthcare workers in
      Auckland, New Zealand: additional justification for assumption of age-determined
      immunity based on local data.
AB  - An outbreak of measles in another region of New Zealand prompted our organization
      to review the measles immunity of healthcare workers. Some studies suggest that
      age-specific immunity cannot be assumed. In our local setting, however, we found
      that 893 (98%) of 912 healthcare workers more than 40 years old tested
      seropositive for measles immunoglobulin G.

PMID- 20804376
TI  - Economic impact of Acinetobacter baumannii infection in the intensive care unit.

PMID- 20804377
TI  - Room decontamination with UV radiation.
AB  - OBJECTIVE: To determine the effectiveness of a UV-C-emitting device to eliminate
      clinically important nosocomial pathogens in a contaminated hospital room.
      METHODS: This study was carried out in a standard but empty hospital room (phase
      1) and in a room previously occupied by a patient with methicillin-resistant
      Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) infection
      (phase 2) in an acute care tertiary hospital in North Carolina from January 21
      through September 21, 2009. During phase 1, 8 x 8 cm Formica sheets contaminated
      with approximately 10(4)-10(5) organisms of MRSA, VRE, multidrug-resistant (MDR)
      Acinetobacter baumannii, or Clostridium difficile spores were placed in a
      hospital room, both in direct line of sight of the UV-C device and behind
      objects. After timed exposure, the presence of the microbes was assessed. During
      phase 2, specific sites in rooms that had housed patients with MRSA or VRE
      infection were sampled before and after UV-C irradiation. After timed exposure,
      the presence of MRSA and VRE and total colony counts were assessed. RESULTS: In
      our test room, the effectiveness of UV-C radiation in reducing the counts of
      vegetative bacteria on surfaces was more than 99.9% within 15 minutes, and the
      reduction in C. difficile spores was 99.8% within 50 minutes. In rooms occupied
      by patients with MRSA, UV-C irradiation of approximately 15 minutes duration
      resulted in a decrease in total CFUs per plate (mean, 384 CFUs vs 19 CFUs; P <
      .001), in the number of samples positive for MRSA (81 [20.3%] of 400 plates vs 2
      [0.5%] of 400 plates; P < .001), and in MRSA counts per MRSA-positive plate
      (mean, 37 CFUs vs 2 CFUs; P < .001). CONCLUSIONS: This UV-C device was effective
      in eliminating vegetative bacteria on contaminated surfaces both in the line of
      sight and behind objects within approximately 15 minutes and in eliminating C.
      difficile spores within 50 minutes.

PMID- 20804378
TI  - Does hand hygiene reduce influenza transmission?

PMID- 20804380
TI  - The neuronal replicator hypothesis.
AB  - We propose that replication (with mutation) of patterns of neuronal activity can
      occur within the brain using known neurophysiological processes. Thereby
      evolutionary algorithms implemented by neuro- nal circuits can play a role in
      cognition. Replication of structured neuronal representations is assumed in
      several cognitive architectures. Replicators overcome some limitations of
      selectionist models of neuronal search. Hebbian learning is combined with
      replication to structure exploration on the basis of associations learned in the
      past. Neuromodulatory gating of sets of bistable neurons allows patterns of
      activation to be copied with mutation. If the probability of copying a set is
      related to the utility of that set, then an evolutionary algorithm can be
      implemented at rapid timescales in the brain. Populations of neuronal replicators
      can undertake a more rapid and stable search than can be achieved by serial
      modification of a single solution. Hebbian learning added to neuronal replication
      allows a powerful structuring of variability capable of learning the location of
      a global optimum from multiple previously visited local optima. Replication of
      solutions can solve the problem of catastrophic forgetting in the stability
      plasticity dilemma. In short, neuronal replication is essential to explain
      several features of flexible cognition. Predictions are made for the experimental
      validation of the neuronal replicator hypothesis.

PMID- 20804381
TI  - A conditional entropy minimization criterion for dimensionality reduction and
      multiple kernel learning.
AB  - Reducing the dimensionality of high-dimensional data without losing its essential
      information is an important task in information processing. When class labels of
      training data are available, Fisher discriminant analysis (FDA) has been widely
      used. However, the optimality of FDA is guaranteed only in a very restricted
      ideal circumstance, and it is often observed that FDA does not provide a good
      classification surface for many real problems. This letter treats the problem of
      supervised dimensionality reduction from the viewpoint of information theory and
      proposes a framework of dimensionality reduction based on class-conditional
      entropy minimization. The proposed linear dimensionality-reduction technique is
      validated both theoretically and experimentally. Then, through kernel Fisher
      discriminant analysis (KFDA), the multiple kernel learning problem is treated in
      the proposed framework, and a novel algorithm, which iteratively optimizes the
      parameters of the classification function and kernel combination coefficients, is
      proposed. The algorithm is experimentally shown to be comparable to or
      outperforms KFDA for large-scale benchmark data sets, and comparable to other
      multiple kernel learning techniques on the yeast protein function annotation
      task.

PMID- 20804382
TI  - A novel recurrent neural network with finite-time convergence for linear
      programming.
AB  - In this letter, a novel recurrent neural network based on the gradient method is
      proposed for solving linear programming problems. Finite-time convergence of the
      proposed neural network is proved by using the Lyapunov method. Compared with the
      existing neural networks for linear programming, the proposed neural network is
      globally convergent to exact optimal solutions in finite time, which is
      remarkable and rare in the literature of neural networks for optimization. Some
      numerical examples are given to show the effectiveness and excellent performance
      of the new recurrent neural network.

PMID- 20804383
TI  - A fast L(p) spike alignment metric.
AB  - The metrization of the space of neural responses is an ongoing research program
      seeking to find natural ways to describe, in geometrical terms, the sets of
      possible activities in the brain. One component of this program is spike metrics
      notions of distance between two spike trains recorded from a neuron. Alignment
      spike metrics work by identifying "equivalent" spikes in both trains. We present
      an alignment spike metric having L(p) underlying geometrical structure; the L(2)
      version is Euclidean and is suitable for further embedding in Euclidean spaces by
      multidimensional scaling methods or related procedures. We show how to implement
      a fast algorithm for the computation of this metric based on bipartite graph
      matching theory.

PMID- 20804384
TI  - Rademacher chaos complexities for learning the kernel problem.
AB  - We develop a novel generalization bound for learning the kernel problem. First,
      we show that the generalization analysis of the kernel learning problem reduces
      to investigation of the suprema of the Rademacher chaos process of order 2 over
      candidate kernels, which we refer to as Rademacher chaos complexity. Next, we
      show how to estimate the empirical Rademacher chaos complexity by well
      established metric entropy integrals and pseudo-dimension of the set of candidate
      kernels. Our new methodology mainly depends on the principal theory of U
      processes and entropy integrals. Finally, we establish satisfactory excess
      generalization bounds and misclassification error rates for learning gaussian
      kernels and general radial basis kernels.

PMID- 20804385
TI  - How are lateral chromatic interactions computed from cone signals?
AB  - A small gray test field superimposed on a large colored background appears tinted
      in a color complementary to that of the surround. We tested the hypothesis
      whether photoreceptor sensitivity in the test field is altered in the presence of
      a colored surround. We investigated this effect using dichoptic viewing
      conditions. With the left eye, subjects viewed a small gray target superimposed
      on a large colored background. The right eye saw a gray target superimposed on a
      large gray background. When the two images were fused, observers perceived one
      homogeneous background and two targets. Observers matched the color of the target
      seen by the right eye to that seen by the left eye. A modified two-stage model
      for chromatic induction assuming that both receptor and postreceptor mechanisms
      contribute to the shift in color was fitted to the matched settings. We find that
      the dichoptic viewing effects presented here are well explained by an
      approximately equal contribution of receptor and postreceptor processes to the
      perceived shift in color.

PMID- 20804386
TI  - Comparing classification methods for longitudinal fMRI studies.
AB  - We compare 10 methods of classifying fMRI volumes by applying them to data from a
      longitudinal study of stroke recovery: adaptive Fisher's linear and quadratic
      discriminant; gaussian naive Bayes; support vector machines with linear,
      quadratic, and radial basis function (RBF) kernels; logistic regression; two
      novel methods based on pairs of restricted Boltzmann machines (RBM); and K
      nearest neighbors. All methods were tested on three binary classification tasks,
      and their out-of-sample classification accuracies are compared. The relative
      performance of the methods varies considerably across subjects and classification
      tasks. The best overall performers were adaptive quadratic discriminant, support
      vector machines with RBF kernels, and generatively trained pairs of RBMs.

PMID- 20804387
TI  - Window-based example selection in learning vector quantization.
AB  - A variety of modifications have been employed to learning vector quantization
      (LVQ) algorithms using either crisp or soft windows for selection of data.
      Although these schemes have been shown in practice to improve performance, a
      theoretical study on the influence of windows has so far been limited. Here we
      rigorously analyze the influence of windows in a controlled environment of
      gaussian mixtures in high dimensions. Concepts from statistical physics and the
      theory of online learning allow an exact description of the training dynamics,
      yielding typical learning curves, convergence properties, and achievable
      generalization abilities. We compare the performance and demonstrate the
      advantages of various algorithms, including LVQ 2.1, generalized LVQ (GLVQ),
      Learning from Mistakes (LFM) and Robust Soft LVQ (RSLVQ). We find that the
      selection of the window parameter highly influences the learning curves but not,
      surprisingly, the asymptotic performances of LVQ 2.1 and RSLVQ. Although the
      prototypes of LVQ 2.1 exhibit divergent behavior, the resulting decision boundary
      coincides with the optimal decision boundary, thus yielding optimal
      generalization ability.

PMID- 20804388
TI  - The regulation of differentiation in mesenchymal stem cells.
AB  - Mesenchymal stromal/stem cells (MSCs) are a population of stromal cells present
      in the bone marrow and most connective tissues, capable of differentiation into
      mesenchymal tissues such as bone and cartilage. MSCs are attractive candidates
      for biological cell-based tissue repair approaches because of their extensive
      proliferative ability in culture while retaining their mesenchymal multilineage
      differentiation potential. In addition to its undoubted scientific interest, the
      prospect of monitoring and controlling MSC differentiation is a crucial
      regulatory and clinical requirement. Hence, the molecular regulation of MSC
      differentiation has been extensively studied. Most of the studies are in vitro,
      because the identity of MSCs in their tissues of origin in vivo remains
      undefined. This review addresses the current knowledge of the molecular basis of
      differentiation of cultured MSCs, with a particular focus on chondrogenesis and
      osteogenesis. Building on the information coming from developmental biology
      studies of embryonic skeletogenesis, several signaling pathways and transcription
      factors have been investigated and shown to play critical roles in MSC
      differentiation. In particular, the Wnt and transforming growth factor-beta/bone
      morphogenetic protein signaling pathways are well known to modulate in MSCs the
      molecular differentiation into cartilage and bone. Relevant to the emerging
      concept of stem cell niches is the demonstration that physical factors can also
      participate in the regulation of MSC differentiation. Knowledge of the regulation
      of MSC differentiation will be critical in the design of three-dimensional
      culture systems and bioreactors for automated bioprocessing through mathematical
      models applied to systems biology and network science.

PMID- 20804404
TI  - The effective therapy of cyclosporine A with drug delivery system in experimental
      colitis.
AB  - Cyclosporine A (CyA) is a useful immunosuppressive agent for steroid-dependent or
      steroid-refractory ulcerative colitis. However, side effects have been reported
      in clinical trials of ulcerative colitis treated with CyA. Biodegradable
      microspheres (MS) have been investigated as drug delivery system. We evaluated
      the effect of a drug delivery system with poly(d,l-lactic acid)-MS containing
      CyA. Colitis was induced in C57BL/6 mice by 3% dextran sulfate sodium (DSS). Mice
      with DSS-induced colitis were treated with oral administration of CyA or CyA-MS:
      CyA (0.2 mg/kg/day)-MS; CyA (2 mg/kg/kg)-MS). Serum levels of CyA were
      significantly less elevated after oral administration of CyA (2 mg/kg/day)-MS
      compared with CyA (2 mg/kg/day) (CyA (2 mg/kg/day), 44.7 +/- 0.8 ng/ml; CyA (2
      mg/kg/day)-MS, 7.7 +/- 1.3 ng/ml). The body weight at day 10 was significantly
      recovered in the mice treated with CyA (0.2 mg/kg/day)-MS and CyA (2 mg/kg/day)
      MS compared with CyA (0). The histological score and myeloperoxidase activity in
      the mice treated with CyA-MS was significantly lower than CyA (0). Gene
      expressions of interleukin-1beta (IL-1beta), IL-6, and CXCL1 in the mice treated
      with CyA (0.2 mg/kg/day)-MS and CyA (2 mg/kg/day)-MS were downregulated compared
      with CyA (0)-MS. CyA-MS might be possible to treat ulcerative colitis effectively
      by decreasing the total dosage without the elevation of the serum level or the
      side effects of CyA.

PMID- 20804405
TI  - Implementation of multidisciplinary advice to allied health care professionals
      regarding the management of their patients with neuromuscular diseases.
AB  - PURPOSE: Patients with neuromuscular diseases (NMDs) do not always receive
      appropriate allied health care. This is partially because of the large
      heterogeneity among these conditions, some of which are quite rare. Individual
      allied health care professionals, therefore, have relatively little opportunity
      to develop relevant experience with these patients. To overcome this problem, we
      developed specialist multidisciplinary advice regarding management of patients
      with NMD for occupational therapy (OT), physical therapy (PT) and speech therapy
      (ST) in a primary care or rehabilitation setting. The aims of the study were to
      explore to what extent this allied health care advice was implemented with a
      focus on the amount of therapy received and to explore possible barriers to
      implementation. METHODS: One-hundred two patients visited the Neuromuscular
      Centre Nijmegen for OT, PT and ST consultations. Integrated allied health care
      advice was written on the basis of these consultations and a multidisciplinary
      meeting. All patients, their therapists and rehabilitation physicians received
      this advice. Following the advice, questionnaires were sent out at baseline and
      at 6 months follow up, collecting data on implementation of the amount of therapy
      suggested and on possible barriers for adherence. RESULTS: Advice for ST and OT
      was fully implemented in primary care, but only partially (58%) in a
      rehabilitation setting. Advice to reduce the amount of PT was implemented in only
      15% of the cases. Possible barriers were related to the advice itself
      (feasibility of treatment duration, correctness and completeness), the patient
      (motivation) and the professional (experience in treatment of NMDs). Therapists
      expressed a desire to have the opportunity to discuss the treatment advice with
      the multidisciplinary team. CONCLUSIONS: The extent to which multidisciplinary
      advice was implemented differed for OT and ST compared to PT and for the setting
      (primary care or rehabilitation). Possible barriers were identified at different
      levels. We recommend follow-up telephone calls to provide therapists opportunity
      for discussion.

PMID- 20804406
TI  - Employment status and work characteristics among adolescents with disabilities.
AB  - PURPOSE: Little is known about the work experiences of youth as they transition
      to adulthood. The purpose of this study is to explore the characteristics
      associated with disabled youth who are employed and the types of employment they
      are engaged in. METHOD: Data were analysed using the 2006 Participation and
      Activity Limitation Survey. Youth aged 15-29 and 20-24 were selected to explore
      the characteristics of adolescents who are employed and where they are working
      (n=2534). RESULTS: Several differences in who was employed and the
      characteristics of their employers were noted between the two age groups.
      Geographic location played a more significant role for employment among youth (15
      19 year olds) with mobility impairments compared to other disability types.
      Employed youth from both age groups had their disability a long time while few
      people who were recently diagnosed were working. Transportation was a significant
      predictor of employment for both age groups. Young adults (20-24) worked more
      hours per week, in different industries, and more of them were self-employed
      compared to the 15-19 year olds. Employment status and work characteristics also
      differed by type of disability. CONCLUSIONS: Rehabilitation and life skills
      counsellors need to pay particular attention to youth who may need extra help in
      gaining employment.

PMID- 20804407
TI  - Counting the invisible: understanding the lives of young people with disabilities
      in Pakistan.
AB  - PURPOSE: To understand the lives of young people with disabilities in Pakistan
      using a household survey. METHOD: Data were collected by administering the survey
      to 1094 urban and rural households randomly selected from nine districts in two
      provinces. The survey had a roster, which captured basic demographic,
      anthropometric, education and labour market status information on all resident
      household members in the sampled households (around 9000 individuals). In
      addition, detailed individual-level questionnaires were administered only to
      those aged between 15 and 60 years. While the survey did not have an exclusive
      focus on issues of disability, the questions used were informative and
      innovative. RESULTS: The findings of this survey emphasise the continued
      marginalisation of young people with disabilities in the areas of education,
      employment and marriage prospects. Additionally, reflections on the research
      process highlight the many challenges entailed in undertaking research on
      disability issues. CONCLUSIONS: Considering the high numbers of people reporting
      difficulties, many of them mild but which have a considerable impact on their
      functioning, there is a need for better health care planning and outreach. Given
      the lack of knowledge about people with disabilities - their incidence and status
      - there is a need for more rigorous research to help develop effective
      interventions.

PMID- 20804412
TI  - Undiagnosed HIV infection among adolescents seeking primary health care in
      Zimbabwe.
AB  - BACKGROUND: Mother-to-child transmission of human immunodeficiency virus (HIV)
      infection was extremely common in southern Africa during the 1990s, and a
      substantial minority of infected infants have survived to reach adolescence
      undiagnosed. Studies have shown a high prevalence of HIV infection in
      hospitalized adolescents who have features associated with long-standing HIV
      infection, including stunting and frequent minor illnesses. We therefore
      investigated the epidemiology of HIV infection at the primary care level.
      METHODS: Adolescents (aged 10-18 years) attending two primary care clinics
      underwent HIV and Herpes simplex virus-2 (HSV-2) serological testing, clinical
      examination, and anthropometry. All were offered routine HIV counseling and
      testing. Patients attending for acute primary care (APC) who were HIV infected
      were asked about their risk factors. RESULTS: Five hundred ninety-four
      participants were systematically recruited (97% participation), of whom 88 (15%)
      were attending for antenatal care. HIV infection prevalence was higher among APC
      attendees than among antenatal care attendees (17% vs 6%; P < .007), but for the
      prevalence of HSV-2 infection, a marker of sexually acquired HIV, the converse
      was true (4% vs 14%; P < .002). Seventy (81%) of 86 HIV-positive APC attendees
      were previously undiagnosed. They had a broad range of presenting complaints,
      with a median CD4 cell count of 329 cells/microL (interquartile range, 176-485
      cells/microL) and a high prevalence of stunting, compared with the corresponding
      prevalence among HIV-negative attendees (40% vs 12%; P < .001). Maternal
      transmission was considered to be likely by 69 (80%) of the 86 HIV-positive APC
      attendees, only one of whom was HSV-2 positive. CONCLUSIONS: Unrecognized HIV
      infection was a common cause of primary care attendance. Routine HIV counseling
      and testing implemented at the primary care level may provide a simple and
      effective way of identifying older long-term survivors of mother-to-child
      transmission before the onset of severe immunosuppression and irreversible
      complications.

PMID- 20804414
TI  - Adolescents and HIV in sub-Saharan Africa: a timely issue and missed opportunity.

PMID- 20804415
TI  - Healthcare workers' perceptions of mandatory vaccination: results of an anonymous
      survey in a German University Hospital.
AB  - Despite decades of effort to encourage healthcare workers (HCWs) to be immunized,
      vaccination rates remain insufficient. Among German HCWs, 831 (68.4%) of 1,215
      respondents supported mandatory vaccinations for HCWs in general. However,
      acceptance of mandatory vaccination varied significantly between physicians and
      nurses and also depended on the targeted disease.

PMID- 20804416
TI  - Influenza vaccination of household contacts of newborns: a hospital-based
      strategy to increase vaccination rates.
AB  - We implemented a hospital-based influenza vaccination program for household
      contacts of newborns. Among mothers not vaccinated prenatally, 44.7% were
      vaccinated through the program, as were 25.7% of fathers. A hospital-based
      program provided opportunities for vaccination of household contacts of newborns,
      thereby facilitating better adherence to national vaccination guidelines.

PMID- 20804419
TI  - Improving success by balanced critical evaluations of assay methods.

PMID- 20804418
TI  - ADP detection technologies.

PMID- 20804420
TI  - An interview with Larry Sklar, Ph.D., and Bruce Edwards, Ph.D. Interview by Vicki
      Glaser.

PMID- 20804413
TI  - Mother-to-child transmission of HIV-2 infection from 1986 to 2007 in the ANRS
      French Perinatal Cohort EPF-CO1.
AB  - BACKGROUND: Management of pregnant women with human immunodeficiency virus (HIV)
      type 2 infection remains unclear because of its low prevalence and important
      differences from HIV-1. METHODS: Pregnant women monoinfected with HIV-2 or HIV-1
      and their infants enrolled in the prospective, national, multicenter French
      Perinatal Cohort between 1986 and 2007. RESULTS: Overall, 2.6% (223/8660) of
      mothers were infected with HIV-2, and they accounted for 3.1% (367/ 11841) of the
      total births. Most were born in sub-Saharan Africa. A higher proportion of HIV-2
      infected mothers than HIV-1-infected mothers had no symptoms, had received no
      antiretroviral therapy at conception (85.9% vs 66.7%), and had received no
      antiretroviral therapy during pregnancy (42.8% vs 19.9%), particularly highly
      active antiretroviral therapy (HAART) (79.7% vs 46.1%), and they had higher CD4
      cell counts near delivery (median, 574 vs 452 cells/mm3; P < .01). If
      antiretroviral therapy was used, it was started at a later gestational age for
      HIV- 2-infected mothers (median, 28 vs 25 weeks; P < .01). HIV-2-infected mothers
      were more likely to deliver vaginally (67.9% vs 49.3%) and to breastfeed (3.6% vs
      0.6%; P < .01), and their infants less frequently received postexposure
      prophylaxis. In the period 2000-2007, the proportion with viral load <100
      copies/mL at delivery was 90.5% of HIV-2-infected mothers, compared with 76.2% of
      HIV-1-infected mothers (P=.1). There were 2 cases of transmission: 1 case in 1993
      occurred following maternal primary infection, and the other case occurred
      postnatally in 2002 and involved a mother with severe immune deficiency. The
      mother-to-child transmission rate for HIV-2 was 0.6% (95% confidence interval,
      0.07%-2.2%). CONCLUSIONS: Care for HIV-2-infected pregnant women rests on expert
      opinion. The mother-to-child transmission residual rate (0.07%-2.2%) argues for
      systematic treatment: protease inhibitor-based HAART for women requiring
      antiretrov

PMID- 20804422
TI  - Identification of substrates of SMURF1 ubiquitin ligase activity utilizing
      protein microarrays.
AB  - The ubiquitin proteasome pathway (UPP) has been implicated in a number of
      pathogenic diseases: cancer, inflammation, metabolic disorders, and viral
      infection. The human genome contains well over 500 genes encoding proteins
      involved in the UPP. Ubiquitin ligases (E3s) comprise the largest subset of these
      genes, and together with an E2 partner, provide the substrate selectivity
      required for regulating cellular proteins through the covalent attachment of
      ubiquitin. Many ligases that have been identified in critical cellular pathways
      have no known substrates. Even those E3s with known substrates may have a yet
      unidentified role in the pathways on which they lie and as such may have
      additional substrates. It is critical to identify these substrates for discovery
      of selective small molecule inhibitors aimed at therapeutic intervention. Other
      methods, such as mass spectrometry, have been utilized for identifying ligase
      substrates, but these are labor-intensive and require a significant investment.
      In this study, we utilized protein microarrays for the identification of
      substrates of the HECT domain E3, Smurf1. Smurf1 is a critical regulator of TGF
      beta and bone morphogenic protein signaling, and has been demonstrated to play a
      role in regulating cell polarity through the degradation of RhoA. We set out to
      identify novel Smurf1 substrates involved in the regulation of the aforementioned
      pathways. Proof-of-principle experiments with known Smurf1 substrates
      demonstrated efficient ubiquitination thereby validating this approach. Assaying
      a human protein microarray for ubiquitination with Smurf1 and the partner E2
      ubiquitin ligase Ubch5 or Ubch7 identified 89 potential substrates of the Smurf1
      E3 activity, which spanned a number of different biological pathways. Substrates
      identified utilizing protein microarray technology have been validated in vitro.
      Here we demonstrate the utility of this approach for identifying substrates of
      particular E2/E3 complexes.

PMID- 20804423
TI  - Anisakidosis: Perils of the deep.
AB  - Anisakidosis, human infection with nematodes of the family Anisakidae, is caused
      most commonly by Anisakis simplex and Pseudoterranova decipiens. Acquired by the
      consumption of raw or undercooked marine fish or squid, anisakidosis occurs where
      such dietary customs are practiced, including Japan, coastal regions of Europe,
      and the United States. Severe epigastric pain, resulting from larval invasion of
      the gastric mucosa, characterizes gastric anisakidosis; other syndromes are
      intestinal and ectopic. Allergic anisakidosis is a frequent cause of foodborne
      allergies in areas with heavy fish consumption or occupational exposure.
      Diagnosis and treatment of gastric disease is usually made by a compatible
      dietary history and visualization and removal of the larva(e) on endoscopy;
      serologic testing for anti-A. simplex immunoglobulin E can aid in the diagnosis
      of intestinal, ectopic and allergic disease. Intestinal and/or ectopic cases may
      require surgical removal; albendazole has been used occasionally. Preventive
      measures include adequately freezing or cooking fish.

PMID- 20804424
TI  - Combination of SMN trans-splicing and a neurotrophic factor increases the life
      span and body mass in a severe model of spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA), a neurodegenerative disease, is the second most
      common genetic disorder and the leading genetic cause of infantile death. SMA
      arises from the loss of Survival Motor Neuron-1 (SMN1), leading to degeneration
      of lower motor neurons and, consequently, the atrophy of voluntary muscles. A
      duplicated copy gene called SMN2 exists in humans. SMN2 is unable to fully
      compensate for the loss of SMN1 because it produces very low levels of functional
      SMN protein due to an alternative splicing event. A C/T transition in SMN2 exon 7
      results in a transcript lacking exon 7 and, therefore, creates a truncated SMN
      protein that cannot fully compensate for the loss of SMN1. However, SMN2 is an
      ideal target for therapeutic strategies that redirect this critical splicing
      event. Previously, we developed the first trans-splicing strategy to increase the
      full-length mRNA and functional SMN protein from the SMN2 gene. To improve the
      trans-splicing efficacy, we then developed a single-vector system that expressed
      a trans-splicing RNA (tsRNA) and an antisense blocking the downstream splice
      site. This single vector greatly enhanced trans-splicing of SMN2 transcripts in
      vitro and in vivo. In this report, we have added a neurotrophic factor [insulin
      like growth factor (IGF)-1] to this single vector to determine whether
      neuroprotection and SMN induction provide greater protection in an SMA animal
      model. Intracerebroventricular injection of the trans-splicing/IGF vector
      significantly increased SMN protein in brain and spinal cord of SMADelta7 mice
      and lessened the severity of disease in a more severe mouse model as evidenced by
      an extension of life span and increased body mass.

PMID- 20804426
TI  - Mucociliary and cough clearance as a biomarker for therapeutic development.
AB  - A workshop/symposium on "Mucociliary and Cough Clearance (MCC/CC) as a Biomarker
      for Therapeutic Development" was held on October 21-22, 2008, in Research
      Triangle Park, NC, to discuss the methods for measurement of MCC/CC and how they
      may be optimized for assessing new therapies designed to improve clearance of
      airway secretions from the lungs. The utility of MCC/CC as a biomarker for
      disease progression and therapeutic intervention is gaining increased recognition
      as a valuable tool in the clinical research community. A number of investigators
      currently active in using MCC/CC for diagnostic or therapeutic evaluation
      presented details of their methodologies. Attendees participating in the workshop
      discussions included those interested in the physiology of MCC/CC, some of who
      use in vitro or animal methods for its study, pharmaceutical companies developing
      muco-active therapies, and many who were interested in establishing the methods
      in their own clinical laboratory. This review article summarizes the
      presentations for the in vivo human MCC/CC methods and the discussions both at
      and subsequent to the workshop between the authors to move forward on a number of
      questions raised at the workshop.

PMID- 20804427
TI  - A computational fluid dynamics model for drug delivery in a nasal cavity with
      inferior turbinate hypertrophy.
AB  - BACKGROUND: Intranasal medications are commonly used in treating nasal diseases.
      However, technical details of the correct usage of these medications for nasal
      cavity with obstruction are unclear. METHODS: A three-dimensional model of nasal
      cavity was constructed from MRI scans of a healthy human subject. Nasal cavities
      corresponding to healthy, moderate, and severe nasal obstruction (NO) were
      simulated by enlarging the inferior turbinate geometrically, which was documented
      by approximately one-third reduction of the minimum cross-sectional area for the
      moderate and two-thirds for the severe obstruction. The discrete phase model
      based on steady-state computational fluid dynamics was used to study the gas
      particle flow. The results were presented with drug particle (from 7 x 10-5 to 10
      7 m) deposition distribution along the lateral walls inside these three nasal
      cavities, and comparisons of the particle ratio escaping from the cavity were
      also presented and discussed. RESULTS: Nasal patency is an essential condition
      that had the most impact on particle deposition of the factors studied; the
      particle percentage escaping the nasal cavity decreased to less than a half and
      one-tenth for the moderately and severely blocked noses. Decreasing of flow rate
      and particle diameter increased the escaping ratio; however, zero escaping
      percentage was detected with the absence of air flow and the effect was less
      noticeable when the particle diameter was very small (<10-6 m). The existence of
      inspiratory flow and head tilt angle helped to improve the particle escaping
      ratio for the healthy nose; however, such changes were not significant for the
      moderately and severely blocked noses. CONCLUSION: When using an intranasal
      medication, it is advisable to have a moderate inspiratory air-flow rate and
      small size particles to improve particle escaping ratio. Various head positions
      suggested by clinicians do not seem to improve the drug escaping ratio
      significantly for the nasal cavities with inferior turbinate hypertrophy.

PMID- 20804428
TI  - Predictors of incorrect inhalation technique in patients with asthma or COPD: a
      study using a validated videotaped scoring method.
AB  - BACKGROUND: Inadequate technique reduces the effects of inhalation medication.
      Errors in inhalation technique have been reported to range up to 85%. Not only
      various patients' characteristics but also the device has an effect on correct
      inhalation technique. The purpose of this study was to determine the effect of
      patients' characteristics and type of inhaler device on inhalation technique in
      patient with asthma or chronic obstructive pulmonary disease (COPD). METHODS: A
      validated scoring method was used that consisted of triple viewing of video
      recorded inhalations, using device-specific checklists. The following patient
      characteristics were investigated: gender, age, education level, diagnosis,
      treatment by a pulmonary physician, previously received inhalation instruction,
      exacerbation frequency, knowledge, self-management competence, pulmonary
      function, and use of multiple inhaler devices. Chi-square statistics were used
      for univariate associations between potential determinants and correctness of
      inhalation technique. Relevant determinants were entered into a multivariate
      logistic regression model. Moreover, inhalation technique errors were examined
      for six inhaler devices: three prefilled dry powder inhalers, one single-dose dry
      powder inhaler, a pressurized metered-dose inhaler (pMDI) and a pMDI with a
      spacer. RESULTS: Overall, 40% of the patients made at least one essential mistake
      in their inhalation technique. Patients who never received inhalation instruction
      and patients who used more than one inhaler device made significantly more errors
      (odds ratio both 2.2). Comparison between devices showed that a correct
      inhalation technique most likely occurred with the use of prefilled dry powder
      devices. CONCLUSION: Incorrect inhalation technique is common among asthma and
      COPD patients in a pulmonary outpatient clinic. Our study suggests that the use
      of prefilled dry powder inhalers as well as inhalation instruction increases
      correct inhalation technique. Simultaneous use of different types of inhalation
      devices has to be discouraged.

PMID- 20804429
TI  - Development of bladder outlet obstruction after a single treatment of prostate
      cancer with high-intensity focused ultrasound: experience with 226 patients.
AB  - PURPOSE: To investigate the occurrence of bladder outlet obstruction (BOO) after
      high-intensity focused ultrasound (HIFU) therapy of prostate cancer, the need for
      secondary transurethral interventions for BOO, and the benefit of transurethral
      resection of the prostate (TURP) before HIFU. PATIENTS AND METHODS: After a
      single HIFU treatment between 2002 and 2007, 226 consecutive patients were
      examined and followed at least 2 years. The Ablatherm Maxis and the Integrated
      Imaging devices were used. The sites of BOO were recorded. RESULTS: Median follow
      up after HIFU was 52 months (range 24-80 mos). BOO developed in 58 (25.66%)
      patients. Repeated BOO episodes were observed in 27 (11.94%), three to seven
      episodes in 13 (5.75%) patients. Patients with repeated BOO were older than
      patients with singular BOO (71.75 +/- 4.97 vs 68.18 +/- 5.03; P = 0.024). In
      primary BOO, multiple sites of obstruction were more often involved than in
      repeated BOO (25/58 vs 8/27). Conversely, isolated bladder neck stenosis was
      predominantly found in patients with >=two episodes of BOO. The rate of primary
      BOO was significantly different between patients who had undergone TURP the same
      day as HIFU or within 2 days of HIFU (33/96; 34.38%) and patients with TURP more
      than 1 month (16/89; 17.98%) before HIFU (P = 0.032). BOO occurred in 21.95%
      (9/41) of the patients who were treated with HIFU only. CONCLUSIONS: BOO after
      HIFU is common, particularly affecting the bladder neck. The risk of repeated BOO
      is associated with age. A longer interval between TURP and HIFU (>1 month) might
      reduce the risk for the development of BOO.

PMID- 20804430
TI  - Treatment of chronic low-back pain: a 1-year or greater follow-up.
AB  - BACKGROUND: Musculoskeletal disorders are the most frequent cause of physical
      disability in developed countries. In particular, lower back pain is very common
      and represents a significant burden both in terms of patient suffering and costs.
      It is important to determine the most effective and efficient interventions in
      the treatment of this condition. PURPOSE: This article presents clinical outcomes
      in patients with chronic lower back pain involving ligamentous pathology treated
      by a physician who specializes in injection therapy for chronic musculoskeletal
      conditions and is able to tailor injection therapy specifically to each
      individual patient. DESIGN: As a retrospective case series, patients from
      outpatient clinics in both rural and one urban centre were assessed, treated, and
      had 1 year or more follow-up. METHODS: Patients were referred by their family
      physician for assessment for chronic lower back pain refractory to conventional
      medical management. OUTCOME MEASURES: Pain and quality of life (QoL) numeric (10
      cm) analog scales (0 = no pain, 10 = the worst pain imaginable; 0 = best quality
      of life, 10 = worst quality of life) were administered pretreatment and 1 year or
      later after the last treatment. RESULTS: One hundred and ninety (190) patients
      were treated during the study period, June 1999-May 2006. Patients whose follow
      up was 1 year or greater from the last treatment were included, leaving 140
      patients available for data analysis. Both pain and QoL scores were significantly
      improved at least 1 year after the last treatment. There were no differences in
      outcomes as a result of age, response to Xylocaine (lidocaine) injection,
      insurance coverage, smoking history, or gender. CONCLUSIONS: This study suggests
      that prolotherapy using a variety of proliferants can be an effective treatment
      for low back pain from presumed ligamentous dysfunction for some patients when
      performed by a skilled practitioner.

PMID- 20804431
TI  - Adverse events associated with acupuncture: a prospective survey.
AB  - OBJECTIVE: The objective of this study was to investigate the adverse events
      associated with acupuncture using a standard record form in order to identify the
      risks of acupuncture therapy and assess their causes. METHODS: Thirteen (13)
      Oriental medicine doctors volunteered to report the number of acupuncture
      treatment sessions administered and patients encountered every week. When adverse
      events occurred, these doctors reported it using a record form that we created.
      The record form contained six major items to be filled out: patient, acupuncture
      treatment, adverse event, causality, person reporting the incident, and
      acupuncturist. RESULTS: In 5 weeks, the 13 Oriental medicine doctors in our study
      conducted 3071 acupuncture treatment sessions on 2226 patients. A total of 99
      adverse events were reported, which is a rate of 3.2 events per 100 treatments.
      Common adverse events were hemorrhage (32%), hematoma (28%), and needle site pain
      (13%). Of the 99 treatments during which an adverse events occurred, 64
      treatments were ended, and 62 of the adverse events diminished or disappeared. Of
      the 35 remaining cases of adverse events in which treatment was continued, 28
      patients had their adverse events diminish or disappear. Causality assessment
      suggested that 47% of adverse events were certainly caused by acupuncture, 45%
      were probably/likely caused by acupuncture, 7% were possibly caused by
      acupuncture, and only 1% of events were unassessable/unclassifiable. CONCLUSIONS:
      Although acupuncture was associated with adverse events, there were no serious
      adverse events experienced by patients this study. If acupuncture treatment is
      administered by a practitioner with enough experience and is conducted in
      accordance with established guidelines, it is a safe treatment method.

PMID- 20804432
TI  - A serological and molecular study of Leishmania infantum infection in cats from
      the Island of Ibiza (Spain).
AB  - The aim of this study was to evaluate the prevalence of Leishmania infantum
      infection within a feline population by serologic and molecular methods and to
      identify associated risk factors. One hundred five cats living outdoors were
      studied. Sera were tested for IgG antibodies against L. infantum, Toxoplasma
      gondii, and feline immunodeficiency virus (FIV) and for the detection of feline
      leukemia virus (FeLV) p27 antigen by enzyme-linked immunosorbent assay (ELISA).
      L. infantum real-time polymerase chain reaction (PCR) was performed on DNA
      extracted from blood. L. infantum and T. gondii seroprevalence rates were 13.2%
      and 55.2%, respectively. The prevalence of L. infantum by PCR was 8.7%. The total
      rate of L. infantum infection derived from seroreactivity and/or positive PCR was
      15.4%. Serology and PCR results were positively associated, and moderate
      agreement (kappa = 0.489) was found between Leishmania ELISA and PCR. No
      statistical association was found between positive Leishmania PCR results and
      gender, clinical status, or T. gondii seropositivity. Six of the 105 cats (5.7%)
      displayed clinical signs compatible with feline cutaneous leishmaniosis, and 4
      out of these 6 cats (66.7%) were found to have Leishmania infection by means of
      serology and/or PCR. Leishmania seropositivity was associated with clinical signs
      of feline cutaneous leishmaniosis (p = 0.029). The prevalence of FeLV p27 antigen
      was 16.2% (17/105) and of FIV antibody was 20.9% (22/105), with coinfection found
      in 9.5% (10/105) of the cats. Leishmania ELISA seroreactivity and positive PCR
      results were statistically associated with FeLV infection and with coinfection of
      both retroviruses but not with a positive FIV status. The high seroprevalence and
      molecular rates of Leishmania infection observed indicate that cats are
      frequently infected with L. infantum, and the association with FeLV suggests a
      potential role for this retrovirus in feline Leishmania infection in endemic
      areas.

PMID- 20804433
TI  - The triple clinicopathologic features to seminal vesicle-sparing radical
      prostatectomy.
AB  - BACKGROUND AND PURPOSE: With the widespread early detection programs for prostate
      cancer, there has been a downward stage migration and a marked decrease in the
      percentage of men with seminal vesicle invasion (SVI) compared with previous
      data. We evaluated clinicopathologic findings that are associated with SVI to
      select patients for potential seminal vesicle-sparing surgery. PATIENTS AND
      METHODS: We reviewed our radical prostatectomy database from 1997 to 2006 to
      evaluate the incidence and clinical correlates of SVI. Variables analyzed
      included serum prostate-specific antigen (PSA) level, clinical stage, percentage
      of positive cores with cancer, Gleason score on biopsy, age, prostate weight, and
      urethral and vesical surgical margins. Statistical analysis included univariate
      and multivariate logistic regressions. RESULTS: Of 267 patients, 32 (12%) had
      SVI. Preoperative PSA level, biopsy Gleason score, and percentage of positive
      cores were highly predictive of SVI on multivariate analysis. SVI was present in
      only 1/98 patients (1.02 %) with biopsy Gleason score <=6, 0/23 patients (0%)
      with serum PSA level <4 ng/mL, and only 1 patient with <=12.8% of positive cores
      on biopsy. In all cases of distal SVI, there was proximal involvement.
      CONCLUSION: Serum PSA level, Gleason score, and percentage of positive cores on
      biopsy are statistically significant predictors of SVI on multivariate analysis.
      Seminal vesiculectomy does not benefit almost 99% of patients with biopsy Gleason
      score <=6, PSA level <4 ng/mL, and with <12% cores with cancer. In cases of
      seminal vesicle-sparing surgery, frozen section of the proximal portion may be of
      adjunct usefulness for the triple.

PMID- 20804434
TI  - Hemostatic sandwich to control percutaneous nephrolithotomy tract bleeding.
AB  - BACKGROUND AND PURPOSE: Significant bleeding necessitating use of a tamponade
      balloon, embolization, or renal exploration is a rare but catastrophic
      complication after percutaneous nephrolithotomy (PCNL). The purpose of this study
      is to review the success of a novel, minimally invasive technique for controlling
      percutaneous tract bleeding that is refractory to conventional measures.
      MATERIALS AND METHODS: A retrospective review was performed on four patients with
      refractory tract hemorrhage that was managed with a novel gelatin matrix
      hemostatic sandwich technique. In this technique, a 5F angiographic reentry
      catheter was placed through the kidney into the bladder and a 22F Councill-tip
      catheter balloon was passed over this catheter and positioned so that the
      inflated balloon would occlude the inner surface of the nephrostomy tract. Next,
      a 16F Councill-tip catheter was placed over a second wire so that the uninflated
      balloon was just underneath the skin surface. Gelatin matrix hemostatic sealant
      was then injected to fill the tract. Inflation of the outer balloon completely
      sealed the tract, completing the hemostatic sandwich. RESULTS: This technique was
      successfully applied to four patients with tract bleeding that would not stop
      with pressure or a conventional nephrostomy tube alone. The average estimated
      blood loss was 562 mL, and three of four patients avoided transfusion. All
      postoperative hemoglobin values stabilized within 2 days of surgery. There were
      no major or minor complications after use of this technique. No patients needed
      angioembolization or renal exploration. CONCLUSIONS: This novel hemostatic
      sandwich technique should be considered as an option for the control of
      refractory tract hemorrhage after PCNL.

PMID- 20804435
TI  - Percutaneous endocystolysis, a safe and minimally invasive treatment for renal
      cysts: a 13-year experience.
AB  - BACKGROUND AND PURPOSE: Renal cysts are the most common form of renal mass with a
      prevalence of 35% in people older than 50 years. Several techniques are used to
      manage symptomatics cysts, from sclerotherapy to open surgery. We present a safe
      and minimally invasive therapeutic alternative: Percutaneous endocystolysis (PE).
      PATIENTS AND METHODS: Between 1995 and 2008, 32 patients were treated for large
      symptomatic Bosniak type I and II renal cysts with the PE technique. Percutaneous
      access was obtained by direct puncture guided by fluoroscopy or ultrasonography,
      percutaneous dilation, and placement of a 28F Amplatz sheath; then a 26F
      resectoscope with a rollerball electrode was introduced into the interior of the
      cyst and the whole internal surface was inspected and cauterized. After
      cauterization, a 20F Foley catheter was placed inside the cyst. Patients were
      discharged the next day, and the catheter was removed in the outpatient facility
      after 7 to 10 postoperative days. The variables of age, cyst volume, operative
      time, and length of hospital stay were statistically analyzed using the Pearson
      linear correlation coefficient. RESULTS: Clinical follow-up ranged from 4 to 162
      months (mean 76 mos). Percutaneous access to the cyst was obtained by blind
      puncture in 7 (21.8%) patients, aided by fluoroscopy in 12 (37.5%) patients, and
      guided by ultrasonography in 13 (40.7%) patients. Clinical improvement was
      observed in all patients with a success rate of 100%. The length of hospital stay
      was 21.7 +/- 8.5 hours (range 9-48 h). The operative time was 41.8 +/- 19.7
      minutes (range 12-94 min). There was a low complication rate associated with the
      transparenchymatous PE procedure. CONCLUSION: PE is a safe, minimally invasive,
      and effective technique for the management of large symptomatic renal cysts and
      is associated with high success rates and low complication rates in long-term
      follow-up.

PMID- 20804436
TI  - Natural orifice translumenal endoscopic surgery: radical prostatectomy in the
      canine model.
AB  - PURPOSE: The goal of this study is to demonstrate the feasibility of
      transurethral radical prostatectomy in the canine model. We describe the surgical
      procedure for natural orifice translumenal endoscopic surgery-radical
      prostatectomy (NOTES-RP). MATERIALS AND METHODS: NOTES-RP was performed on six
      nonsurvival male canines. The 100 watt holmium:yttrium-aluminum-garne laser, 550
      MUm end-firing fiber, 28F laser resectoscope, 7F stabilizing catheter, and
      continuous irrigation were used to radically resect the prostate. A Vest
      vesicourethral anastomosis was performed using a laparoscopic suture device that
      was delivered through the nephroscope. In the initial cases, the prostate was
      removed manually; for the last two cases, the prostate was removed endoscopically
      with a tissue morcellator. RESULTS: NOTES-RP was successfully executed in all
      canines. Visualization was not obscured by bleeding. Dissection times ranged from
      40 to 120 minutes. Fluid absorption was problematic in cases lasting more than 1
      hour, because of the intraperitoneal location of the canine prostate and bladder.
      CONCLUSIONS: The feasibility and technique of NOTES-RP was successfully
      demonstrated in the living canine model.

PMID- 20804437
TI  - Does recurrent aphthous stomatitis affect quality of life? A prospective study
      with 128 patients evaluating different treatment modalities.
AB  - INTRODUCTION: Quality of life measures are increasingly being used in the
      evaluation of oral disease outcome. To date, there has been less focus on oral
      health-related quality of life (OHR-QoL) measures for oral diseases in
      dermatologic literature. OBJECTIVE: To test whether patients with recurrent
      aphthous stomatitis (RAS) report a lower OHR-QoL than the general population and
      to evaluate therapeutic regimens for RAS by using OHR-QoL measures. METHOD: A
      total of 128 patients and 40 controls were enrolled. A questionnaire entitled the
      14-item oral health impact profile (OHIP-14) was completed. Forty-three (33%) of
      the patients were followed-up and completed the OHIP-14 following treatment.
      RESULTS: The median total score of patients on colchicine before treatment was
      21. Following use of colchicine, the total score was 10. There was a significant
      difference concerning the impact of oral health following use of oral colchicine.
      However, no reduction of OHIP-14 scores was observed in the topical treatment
      group. CONCLUSION: When the influence of one of the most common oral diseases
      such as RAS on OHR-QoL was taken into consideration, OHR-QoL provides an
      additional dimension that may help to improve the impact of a disease on an
      individual's life. In relation to this, colchicine seems to be one of the most
      effective management strategies used in RAS.

PMID- 20804438
TI  - Differentiation of the toxicities of silver nanoparticles and silver ions to the
      Japanese medaka (Oryzias latipes) and the cladoceran Daphnia magna.
AB  - Silver nanoparticles (AgNPs) are increasingly used in various fields. However,
      little is known about the environmental effects of widespread use of products
      containing AgNPs. The objective of this study was to determine the ecotoxicity
      caused by AgNPs. The 48-h effective concentration 50 (EC(50)) values for Daphnia
      magna of suspensions of 60 nm and 300 nm AgNPs were 1.0 (95% confidence interval
      [CI] = 0.1-1.3) and 1.4 (95% CI = 0.3-2.1) MUg Ag/l, respectively. The 96 h
      LC(50) values for Oryzias latipes of 60 nm and 300 nm AgNP suspensions were 28
      (95% CI = 23-34) and 67 (95% CI = 45-108) MUg Ag/l, respectively. To show that
      toxicity is caused only by Ag(+) and not by AgNPs, Ag(+) was adsorbed onto the
      synthesized sorbents packed in a column and D. magna was exposed to the column
      passed-300 nm AgNP suspensions. There was no acute toxicity with the AgNP
      suspensions not containing Ag(+).

PMID- 20804439
TI  - Multi-walled carbon nanotubes induce oxidative stress and apoptosis in human lung
      cancer cell line-A549.
AB  - Multi-walled carbon-nanotubes (MWCNTs)-induced apoptotic changes were studied in
      human lung epithelium cell line-A549. Non-cytotoxic doses of MWCNTs were
      identified using tetrazolium bromide salt (MTT) and lactate dehydrogenase (LDH)
      release assays. Cells were exposed to MWCNTs (0.5-100 MUg/ml) for 6-72 h.
      Internalization and characterization of CNTs was performed by electron
      microscopy. Apoptotic changes were estimated by nuclear condensation, DNA
      laddering, and confirmed by expression of associated markers: p(53),
      p(21WAF1/CIP1), Bax, Bcl(2) and activated caspase-3. MWCNTs induced the
      production of reactive oxygen species and malondialdehyde along with significant
      decrease in the activity of catalase and glutathione. MWCNTs-induced ROS
      generation was found not to be associated with the mitochondrial activity. In
      general, the changes were significant at 10 and 50 MUg/ml only. Results indicate
      the involvement of oxidative stress and apoptosis in A549 cells exposed to
      MWCNTs. Our studies provide insights of the mechanisms involved in MWCNTs-induced
      apoptosis at cellular level.

PMID- 20804440
TI  - Development and characterization of sponge-like acyclovir ocular minitablets.
AB  - For the treatment of ocular keratitis acyclovir, as a highly specific inhibitor
      of herpes virus replication, is applied topically into the eye. The objective of
      this study was to design and evaluate freeze-dried, bioadhesive and biodegredable
      acyclovir ocular minitablets for prolonged local drug action. The sponge-like
      nature of the lyophilized ocular minitablets ensures rapid hydration and gelation
      of these tablets in the eye and thus would reduce the foreign body sensation. The
      polymers used were sodium carboxymethylcellulose (NaCMC),
      hydroxypropylmethylcellulose (HPMC), xanthan gum, chitosan and Carbopol 943P. The
      minitablets were evaluated for drug content, weight variation, bioadhesion, water
      uptake and in vitro drug release. In addition, the rheological characteristics of
      the polymers solutions were investigated. Rheological data revealed that all
      tested polymers exhibited pseudoplastic behaviour which is required to minimize
      interference with blinking. Drug release was found to be affected by the type and
      concentration of polymer. The order of sustainment was chitosan > xanthan > HPMC
      > Carbopol > NaCMC. Water uptake study, dissolution rate of the polymers and
      viscosity measurements could explain the different release profiles of the drug
      from the polymers. Chitosan minitablet was chosen for its significant sustained
      release and good bioadhesive property for in vivo study in rabbits. The tablet
      showed a good permeation into the cornea in comparison to the commercially
      available Zovirax((r)) eye ointment. In conclusion, chitosan ocular minitablets
      containing acyclovir could be considered as a promising sustained drug delivery
      system for ocular keratitis treatment.

PMID- 20804441
TI  - Thermotactile thresholds at the fingertip: effect of contact area and contact
      location.
AB  - Thresholds for the detection of changes in temperature are used to indicate
      neuropathy, but a variety of different contact areas and contact locations are
      used. This study was designed to determine the effects of variations in contact
      area and contact location on both warm and cool thresholds at the fingertip. With
      20 healthy subjects (10 females and 10 males aged 20-30 years), warm thresholds
      and cool thresholds were determined in two separate sessions using the method of
      limits. In the first part of each session, thresholds were determined around the
      centre of the whorl using circular contactors with five different diameters (3,
      6, 9, 12, and 55 mm). In the second part of each session, thresholds were
      determined using two contactors (6- and 12-mm diameter) at three locations along
      the fingertip: (i) distal (5 mm from the nail), (ii) middle (centre of whorl),
      and (iii) proximal (3 mm from the distal interphalangeal joint). With increasing
      contact area, the warm thresholds decreased, the cool thresholds increased, and
      the inter-subject variability in both warm and cool thresholds decreased. Using
      the 6-mm diameter contactor, warm thresholds were independent of location but
      cool thresholds increased from distal to proximal locations. It is concluded that
      temperature sensitivity at the fingertip increases with increasing area of
      contact, with the variability in thresholds consistent with the existence of warm
      and cool "insensitive fields". The findings show that the influence of contact
      area and contact location should be considered when assessing thermotactile
      thresholds at the fingertip.

PMID- 20804442
TI  - Standardization of the Arabic version of the Voice Handicap Index: an
      investigation of validity and reliability.
AB  - Validity and reliability of the Arabic version of the VHI (VHI-Arab) were
      investigated. Possible effects of participant-inherent factors (i.e. age, sex) on
      participant (77 females, 35 males) responses were also investigated. Results
      showed high internal consistency (Cronbach's alpha r > 0.857 for all scores).
      Test-retest reliability was found to be strong (r > 0.87 for all scores).
      Validity results indicated significant moderate correlations between total VHI
      score and responses to severity (r = 0.521, P = 0.015) and satisfaction (r =
      20.556, P = 0.009) questions. VHI-Arab was found to be unaffected by age (P >
      0.10 for all scores) or sex (P > 0.05). This study produced a valid and reliable
      instrument for measuring participation restriction in Arabic-speaking individuals
      with voice disorders.

PMID- 20804443
TI  - Insulin pharmacokinetics following dosing with Technosphere insulin in subjects
      with chronic obstructive pulmonary disease.
AB  - OBJECTIVES: Insulin exposure after inhalation has been reported to be altered
      significantly in subjects with chronic obstructive pulmonary disease (COPD). In
      this study, the rate and extent of insulin exposure was compared in healthy
      volunteers and subjects with COPD following administration of Technosphere *
      Insulin (TI), a dry powder insulin formulation for pulmonary delivery. METHODS:
      Insulin pharmacokinetics were evaluated in an open-label, single-dose,
      hyperinsulinemic-euglycemic glucose clamp study in 19 nondiabetic, nonsmoking
      healthy subjects (mean age [+/-SD] = 50.9 +/- 14.1 years, body mass index = 29.1
      +/- 3.5 kg/m(2), forced expiratory volume in 1 second (FEV(1)) = 3.52 +/- 1.02 L)
      and 17 nondiabetic subjects with mild-to-moderate COPD (mean age = 60.0 +/- 9.0
      years, body mass index = 28.5 +/- 5 kg/m(2), FEV(1) = 2.56 +/- 0.83 L). Subjects
      received a single 30-U dose of TI. Serial blood samples were obtained for insulin
      and C-peptide determination through 480 min after dosing. Insulin concentrations
      were adjusted for endogenous insulin by C-peptide correction; pharmacokinetic
      parameters were estimated using the corrected values. RESULTS: For the COPD and
      non-COPD groups, respectively, mean peak insulin (C(max)) was 34.7 uU/mL and 39.5
      uU/mL (p = 0.29), median t(max) was 15 and 12 min (p = 0.24), and mean insulin
      exposure from time 0 to 240 min (AUC(0-240)) was 2037 uU/mL . min and 2279 uU/mL
      . min (p = 0.47). Cough was the most common respiratory adverse event observed.
      One instance of hypoglycemia was reported and was attributed to trial procedure.
      CONCLUSIONS: The rapid insulin absorption and the resulting insulin
      pharmacokinetic profile following TI inhalation were not significantly altered in
      the mild-to-moderate COPD population studied; however, long-term safety and
      efficacy of TI have not been established in patients with mild or moderate COPD.
      Longer-term experience is needed to fully characterize the effects of COPD on
      insulin PK following TI administration.

PMID- 20804444
TI  - Diclofenac potassium liquid-filled soft gelatin capsules for the treatment of
      postbunionectomy pain.
AB  - OBJECTIVE: Diclofenac potassium liquid-filled soft gelatin capsule (DPSGC) is a
      rapidly absorbed formulation of diclofenac approved for the treatment of mild to
      moderate acute pain in adults (>=18 years of age). The objective of this study
      was to investigate the efficacy and safety of DPSGC 25 mg in a multicenter,
      randomized, double-blind, placebo-controlled study in patients experiencing pain
      following first metatarsal bunionectomy. RESEARCH DESIGN AND METHODS: Patients
      experiencing a requisite level of pain (>=4 based on an 11-point numeric pain
      rating scale [NPRS]; 0 = no pain, 10 = worst pain possible) on the day following
      surgery were randomized to receive DPSGC 25 mg or placebo. Patients received a
      second dose (remedication) on request or at 8 hours postdose followed by
      additional doses every 6 hours through the end of postsurgery Day 4. Rescue
      medication (hydrocodone/acetaminophen) was available as needed after the second
      dose. CLINICAL TRIAL REGISTRATION: NCT00375934. MAIN OUTCOME MEASURE: The primary
      efficacy endpoint was the average NPRS score over the 48 hour inpatient multiple
      dose period. RESULTS: DPSGC provided a significant improvement in mean 48 hour
      NPRS scores over placebo (3.29 vs 5.74, respectively; p < 0.0001), as well as for
      summed pain intensity difference (203.1 vs 86.6; p < 0.0001). Patients treated
      with DPSGC experienced a faster onset of meaningful pain relief compared with
      placebo (p = 0.0034). Rescue medication use on Day 1 and Day 2 was reduced in the
      DPSGC group compared with placebo (53.5% vs 92.1% on Day 1; 30.3% vs 67.3% on Day
      2; p < 0.0001). DPSGC was well tolerated and no patients treated with DPSGC
      reported serious adverse events. As with any study, there are potential
      limitations including study design and patient population. CONCLUSION: These
      results indicate that DPSGC reduced pain in patients who underwent bunionectomy
      and this novel formulation of diclofenac potassium may be a practical option for
      treating mild to moderate acute pain.

PMID- 20804445
TI  - Saxagliptin and metformin XR combination therapy provides glycemic control over
      24 hours in patients with T2DM inadequately controlled with metformin.
AB  - OBJECTIVE: To assess 24-hour glycemic control with saxagliptin compared with
      placebo as add-on treatment to metformin in patients with type 2 diabetes
      mellitus (T2DM) and inadequate glycemic control. RESEARCH DESIGN AND METHODS:
      This was a 4-week, multicenter, randomized, double-blind, placebo-controlled
      Phase IIIb trial comparing the antihyperglycemic activity of saxagliptin 5 mg
      once daily in combination with a stable dose of metformin extended release (XR)
      vs. placebo in combination with metformin XR in patients with T2DM inadequately
      controlled (screening glycated hemoglobin [HbA(1c)] 7-10%) with stable doses of
      metformin immediate release or metformin XR >= 1500 mg/day. Ninety-three adult
      patients were randomized and received treatment. The primary outcome measure was
      change from baseline to week 4 in 24-hour mean weighted glucose (MWG). RESULTS:
      The reduction from baseline in 24-hour MWG was significantly greater for
      saxagliptin 5 mg + metformin XR (-13.8 mg/dL; -0.77 mmol/L) compared with placebo
      + metformin XR (3.0 mg/dL; 0.17 mmol/L) (p = 0.0001). At week 4, the mean
      decrease in plasma glucose was sustained through a 24-hour period in saxagliptin
      treated patients. Treatment with saxagliptin 5 mg + metformin XR resulted in
      significant mean reductions from baseline in 4-hour mean weighted postprandial
      glucose (PPG), 2-hour PPG, 3-day average mean daily glucose, and fasting plasma
      glucose levels compared with placebo + metformin XR (p <= 0.001). The proportion
      of adverse events (AEs) was similar in the two treatment groups, with no reported
      hypoglycemic AEs in saxagliptin-treated patients. The 4-week evaluation period
      may have been insufficient to evaluate longer term effects on hyperglycemia or to
      identify additional AEs. CONCLUSIONS: In patients with T2DM treated with
      metformin XR, saxagliptin 5 mg orally administered once daily in the evening for
      4 weeks effectively lowered plasma glucose concentrations through the 24-hour
      dosing interval and was well tolerated.

PMID- 20804446
TI  - Empowerment of people with a long-term work disability: development of the
      'VrijBaan' questionnaire.
AB  - PURPOSE: To develop an instrument that measures empowerment among people with a
      long-term work disability. METHODS: A six-dimension empowerment model was chosen
      as a theoretical framework. These dimensions are as follows: competence, self
      determination, meaning, impact, positive identity and group orientation. A
      literature search was conducted to find instruments that currently are being used
      to measure one or more of these constructs. Validated and applicable instruments
      from this search were used in a preliminary questionnaire. A pilot test was
      conducted consulting the target population and experts. On basis of changes from
      this pilot, a concept questionnaire was conducted. In a field test, this
      questionnaire was sent to 976 subjects who followed a vocational rehabilitation
      course in the years 2001-2003. Item-total correlations and factor analyses were
      performed on the collected data to reduce the number of items. Factor analysis
      was performed, and internal consistency was determined to get insight into the
      psychometric properties of the final questionnaire. RESULTS: From all subjects
      who were approached, 385 (39%) returned usable questionnaires that could be
      analysed. Item reduction by item-total correlations and factor analysis resulted
      in a final questionnaire consisting of 62 items divided over the six subscales.
      Internal consistency of the subscales was good: all subscales had Cronbach's
      alphas between 0.80 and 0.91. Some inter-correlation existed between the
      subscales competence, self-determination and impact. CONCLUSIONS: The 'VrijBaan'
      questionnaire was developed to measure empowerment among people with a long-term
      work disability. Although the results support the internal consistency of the
      subscales, further psychometric work is needed to improve the quality of this
      questionnaire.

PMID- 20804447
TI  - Self-concept of adults with cerebral palsy.
AB  - PURPOSE: To describe the self-concept of adults with cerebral palsy (CP). METHOD:
      Cross-sectional design included the Tennessee Self-Concept Scale, version 2
      (TSCS:2), Functional Independence Measure (FIMTM), Beck Depression Index II
      (BDI(r)-II), Craig Hospital Inventory of Environmental Factors (CHIEF), Diener's
      Satisfaction with Life Scale (SWLS), Gross Motor Functional Classification System
      (GMFCS) levels and demographic questions. RESULTS: One hundred and two people
      with CP (52 females, mean age=26) participated. Thirty-eight participants had
      unreliable answers as indicated by validity scales and were excluded from the
      analysis. Ten participants had high self-concept; 41 had average self-concept and
      13 had low total self-concept. Self-concept had a fair and inverse association
      with the BDI-II (Pearson's r= -0.3, p<0.01) and a moderate and direct association
      with the SWLS (Pearson's r=0.4, p<0.001). Self-concept was not associated with
      GMFCS level or FIM score. Family and Personal sub-domain scores were lowest sub
      domain scores for people with low self-concept (p<0.01). CONCLUSION: The majority
      of the participants in this sample had a healthy self-concept; and self-concept
      was not associated with severity of CP, but with lack of depression and life
      satisfaction. Results suggest the need for family centred care into adulthood.

PMID- 20804448
TI  - Effect of orlistat-assisted weight loss on endothelium-dependent vasodilation in
      obese Chinese subjects with hypertension.
AB  - The present study aims to evaluate the effects of orlistat-assisted weight loss
      on endothelium-dependent vasodilation by ultrasonography in obese Chinese
      subjects with hypertension. Thirty obese hypertensive patients (mean age: 46.6 +/
      10.3 yr, male:12) were given 120 mg of orlistat 120 mg three times daily for 12
      weeks, without a concomitant hypocaloric diet or anti-hypertensive drugs. Fifteen
      concurrent blood pressure, age, and gender-matched, nonobese hypertensive
      patients (mean age: 46.6 +/- 11.3 yr, male:6) served as the control. The height,
      body weight, waist circumference (WC), and blood pressure were measured and flow
      mediated dilation (FMD) and the nitroglycerin-mediated dilation (NMD) of brachial
      artery was determined by high-resolution ultrasound before and after 12 weeks
      treatment with orlistat. The baseline parameters were comparable between the two
      groups, while body mass index (BMI) and WC were greater in the obese group (p <
      0.01). Before treatment, the brachial artery diameter was increased by 9.6%
      following reactive hyperemia in the obese group, significantly lower than that in
      the control group (13.3%, P < 0.01). Nitroglycerin-mediated dilation was not
      difference between the two groups. After 12 weeks of orlistat treatment, the
      brachial artery diameter was increased by 14.2%, and the FMD was significantly
      improved (P < 0.01), associated with a significant reduction in weight, BMI, WC,
      and blood pressures. Nitroglycerin-mediated dilation was not significantly
      affected. On multiple regression analysis, improvement in FMD was determined by
      change of body weight (Beta = -0.555, P = 0.001), after adjustments for height,
      heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and
      WC. Orlistat can effectively reduce body weight and blood pressure and improve
      endothelium-dependent FMD in obese Chinese hypertensives.

PMID- 20804449
TI  - Antagonism of eosinophil accumulation in asthma.
AB  - There is considerable evidence that implicates eosinophils as important effector
      cells and immunomodulators in the inflammation characteristic of asthma. Numerous
      in vitro and animal studies have demonstrated essential roles for cell adhesion
      molecules in eosinophil adhesion and transendothelial migration including the
      selectins, ICAM-1, VCAM-1 together with many of the 1 and beta2 integrins. A
      large body of evidence has also implicated several cytokines and chemokines in
      the selective recruitment of eosinophils to sites of asthmatic inflammation.
      Biopharmaceutical approaches have been used to identify inhibitory molecules that
      target key elements in the processes controlling eosinophil accumulation in
      asthma. This review will summarise, the problems and successes regarding recent
      patents and developments in adhesion-based therapeutic strategies aimed at
      reducing eosinophil-mediated inflammation in the asthmatic lung.

PMID- 20804450
TI  - Daclizumab: a potential asthma therapy?
AB  - Airways inflammation in asthma is triggered and maintained by CD4+ (Th2) cells
      which are activated by IL-2 and stimulate the eosinophilic inflammation, IgE
      secretion and mucus hyperproduction. Current anti-inflammatory therapies include
      inhaled corticosteroids, and leukotriene modifiers but they are not universally
      effective. IL-2 pathway inhibition might represent a potent anti-inflammatory
      therapy in asthma given the cytokine early role in the asthma complex
      inflammatory cascade and daclizumab which is a IL-2R blocker currently used as an
      immunsupressor in organ transplantation might be a potential asthma therapy. This
      is review on the pathogenic role of IL-2, on the therapeutic potential of
      daclizumab and on its related patents.

PMID- 20804451
TI  - Review article: stem cell therapies for inflammatory bowel disease - efficacy and
      safety.
AB  - BACKGROUND: Drugs available for the treatment of inflammatory bowel disease fail
      to induce and maintain remission in a significant number of patients. AIM: To
      assess the value of stem cell therapies for treatment of inflammatory bowel
      disease based on published studies. METHODS: Publications were identified through
      a MEDLINE search using the Medical Subject Heading terms: inflammatory bowel
      diseases, or Crohn's disease, or ulcerative colitis, and stem cell, or stromal
      cell or transplant. RESULTS: Haematopoietic stem cell therapy as a primary
      treatment for inflammatory bowel disease was originally supported by animal
      experiments, and by remissions in patients undergoing transplant for
      haematological disorders. Later, transplantation specifically performed for
      patients with refractory Crohn's disease showed long-lasting clinical remission
      and healing of inflammatory intestinal lesions. Use of autologous
      nonmyeloablative regimens and concentration of the procedures in centres with
      large experience are key in reducing treatment-related mortality. Initial trials
      of mesenchymal stem cell therapy with local injection in Crohn's perianal
      fistulas had positive results. CONCLUSIONS: Autologous haematopoietic stem cell
      transplant changes the natural course of Crohn's disease, and may be a
      therapeutic option in patients with refractory disease if surgery is not feasible
      due to disease location or extension.

PMID- 20804452
TI  - The conformation of a nascent polypeptide inside the ribosome tunnel affects
      protein targeting and protein folding.
AB  - In this report, we describe insights into the function of the ribosome tunnel
      that were obtained through an analysis of an unusual 25 residue N-terminal motif
      (EspP(1-25) ) associated with the signal peptide of the Escherichia coli EspP
      protein. It was previously shown that EspP(1-25) inhibits signal peptide
      recognition by the signal recognition particle, and we now show that fusion of
      EspP(1-25) to a cytoplasmic protein causes it to aggregate. We obtained two lines
      of evidence that both of these effects are attributable to the conformation of
      EspP(1-25) inside the ribosome tunnel. First, we found that mutations in EspP(1
      25) that abolished its effects on protein targeting and protein folding altered
      the cross-linking of short nascent chains to ribosomal components. Second, we
      found that a mutation in L22 that distorts the tunnel mimicked the effects of the
      EspP(1-25) mutations on protein biogenesis. Our results provide evidence that the
      conformation of a polypeptide inside the ribosome tunnel can influence protein
      folding under physiological conditions and suggest that ribosomal mutations might
      increase the solubility of at least some aggregation-prone proteins produced in
      E. coli.

PMID- 20804453
TI  - Substrate path in the AcrB multidrug efflux pump of Escherichia coli.
AB  - A major tripartite multidrug efflux pump of Escherichia coli, AcrAB-TolC, confers
      resistance to a wide variety of compounds. The drug molecule is captured by AcrB
      probably from the periplasm or the periplasm/inner membrane interface, and is
      passed through AcrB and then TolC to the medium. Currently, there exist numerous
      crystallographic and mutation data concerning the regions of AcrB and its
      homologues that may interact with substrates. Starting with these data, we
      devised fluorescence assays in whole cells to determine the entire substrate path
      through AcrB. We tested 48 residues in AcrB along the predicted substrate path
      and 25 gave positive results, based on the covalent labelling of cysteine
      residues by a lipophilic dye-maleimide and the blocking of Nile red efflux by
      covalent labelling with bulky maleimide reagents. These residues are all located
      in the periplasmic domain, in regions we designate as the lower part of the large
      external cleft, the cleft itself, the crystallographically defined binding
      pocket, and the gate between the pocket and the funnel. Our observations suggest
      that the substrate is captured in the lower cleft region of AcrB, then
      transported through the binding pocket, the gate and finally to the AcrB funnel
      that connects AcrB to TolC.

PMID- 20804454
TI  - Clinical trial: endoscopic evaluation of naproxen etemesil, a naproxen prodrug,
      vs. naproxen - a proof-of-concept, randomized, double-blind, active-comparator
      study.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs are associated with upper
      gastrointestinal mucosal injury. Naproxen etemesil is a lipophilic, non-acidic,
      inactive prodrug of naproxen that is hydrolysed to pharmacologically active
      naproxen once absorbed. We hypothesized that with lesser topical exposure to
      naproxen from the prodrug, there would be reduced gastroduodenal mucosal injury
      compared with naproxen. AIM: To compare the degree of endoscopic mucosal damage
      of naproxen etemesil vs. naproxen. METHODS: This multicentre, randomized, double
      blind, double-dummy trial compared oral naproxen etemesil 1200 mg twice daily (n
      = 61) with naproxen 500 mg twice daily (n = 59) for 7.5 days in 120 healthy
      subjects (45-70 years; mean 51 years; 58% female) with baseline total modified
      gastroduodenal Lanza score <= 2 (no erosions/ulcers) on endoscopy. The primary
      endpoint was mean total modified gastroduodenal Lanza score on day 7. A secondary
      endpoint was incidence of gastric ulcers. RESULTS: The day 7 mean total modified
      gastroduodenal Lanza score was 2.8 +/- 1.7 for naproxen etemesil vs. 3.5 +/- 2.0
      for naproxen (P = 0.03), and significantly fewer naproxen etemesil-treated
      subjects (3.3%) developed gastric ulcers compared with naproxen-treated subjects
      (15.8%) (P = 0.02). CONCLUSION: In this first proof-of-concept study, naproxen
      etemesil was associated with significantly lower gastroduodenal mucosal injury
      compared with naproxen after 7 days of exposure ( CLINICAL TRIAL NUMBER:
      NCT00750243).

PMID- 20804455
TI  - Multiple features that distinguish unilateral incongruity and self
      incompatibility in the tomato clade.
AB  - Wild tomato species in Solanum Section Lycopersicon often exhibit two types of
      reproductive barriers: self-incompatibility (SI) and unilateral incompatibility
      or incongruity (UI), wherein the success of an inter-specific cross depends on
      the direction of the cross. UI pollen rejection often follows the 'SI * SC' rule,
      i.e. pistils of SI species reject the pollen of SC (self-compatible) species but
      not vice versa, suggesting that the SI and UI pollen rejection mechanisms may
      overlap. In order to address this question, pollen tube growth was measured after
      inter-specific crosses using wild tomato species as the female parents and pollen
      from cultivated tomato (Solanum lycopersicum). Two modes of UI pollen rejection,
      early and late, were observed, and both differed from SI pollen rejection. The
      structure and expression of known stylar SI genes were evaluated. We found that S
      RNase expression is not required for either the early or late mode of UI pollen
      rejection. However, two HT family genes, HT-A and HT-B, map to a UI QTL.
      Surprisingly, we found that a gene previously implicated in SI, HT-B, is mutated
      in both SI and SC S. habrochaites accessions, and no HT-B protein could be
      detected. HT-A genes were detected and expressed in all species examined, and may
      therefore function in both SI and UI. We conclude that there are significant
      differences between SI and UI in the tomato clade, in that pollen tube growth
      differs between these two rejection systems, and some stylar SI factors,
      including S-RNase and HT-B, are not required for UI.

PMID- 20804456
TI  - The PAM1 gene of petunia, required for intracellular accommodation and
      morphogenesis of arbuscular mycorrhizal fungi, encodes a homologue of VAPYRIN.
AB  - Most terrestrial plants engage into arbuscular mycorrhizal (AM) symbiosis with
      fungi of the phylum Glomeromycota. The initial recognition of the fungal symbiont
      results in the activation of a symbiosis signalling pathway that is shared with
      the root nodule symbiosis (common SYM pathway). The subsequent intracellular
      accommodation of the fungus, and the elaboration of its characteristic feeding
      structures, the arbuscules, depends on a genetic programme in the plant that has
      recently been shown to involve the VAPYRIN gene in Medicaco truncatula. We have
      previously identified a mutant in Petunia hybrida, penetration and arbuscule
      morphogenesis 1 (pam1), that is defective in the intracellular stages of AM
      development. Here, we report on the cloning of PAM1, which encodes a VAPYRIN
      homologue. PAM1 protein localizes to the cytosol and the nucleus, with a
      prominent affinity to mobile spherical structures that are associated with the
      tonoplast, and are therefore referred to as tonospheres. In mycorrhizal roots,
      tonospheres were observed in the vicinity of intracellular hyphae, where they may
      play an essential role in the accommodation and morphogenesis of the fungal
      endosymbiont.

PMID- 20804457
TI  - Intragenic allele pyramiding combines different specificities of wheat Pm3
      resistance alleles.
AB  - Some plant resistance genes occur as allelic series, with each member conferring
      specific resistance against a subset of pathogen races. In wheat, there are 17
      alleles of the Pm3 gene. They encode nucleotide-binding (NB-ARC) and leucine-rich
      repeat (LRR) domain proteins, which mediate resistance to distinct race spectra
      of powdery mildew. It is not known if specificities from different alleles can be
      combined to create resistance genes with broader specificity. Here, we used an
      approach based on avirulence analysis of pathogen populations to characterize the
      molecular basis of Pm3 recognition spectra. A large survey of mildew races for
      avirulence on the Pm3 alleles revealed that Pm3a has a resistance spectrum that
      completely contains that of Pm3f, but also extends towards additional races. The
      same is true for the Pm3b and Pm3c gene pair. The molecular analysis of these
      allelic pairs revealed a role of the NB-ARC protein domain in the efficiency of
      effector-dependent resistance. Analysis of the wild-type and chimeric Pm3 alleles
      identified single residues in the C-terminal LRR motifs as the main determinant
      of allele specificity. Variable residues of the N-terminal LRRs are necessary,
      but not sufficient, to confer resistance specificity. Based on these data, we
      constructed a chimeric Pm3 gene by intragenic allele pyramiding of Pm3d and Pm3e
      that showed the combined resistance specificity and, thus, a broader recognition
      spectrum compared with the parental alleles. Our findings support a model of
      stepwise evolution of Pm3 recognition specificities.

PMID- 20804458
TI  - The multiple origins of aluminium resistance in hexaploid wheat include Aegilops
      tauschii and more recent cis mutations to TaALMT1.
AB  - Acid soils limit plant production worldwide because their high concentrations of
      soluble aluminium cations (Al(3+) ) inhibit root growth. Major food crops such as
      wheat (Triticum aestivum L.) have evolved mechanisms to resist Al(3+) toxicity,
      thus enabling wider distribution. The origins of Al(3+) resistance in wheat are
      perplexing because all progenitors of this hexaploid species are reportedly
      sensitive to Al(3+) stress. The large genotypic variation for Al(3+) resistance
      in wheat is largely controlled by expression of an anion channel, TaALMT1, which
      releases malate anions from the root apices. A current hypothesis proposes that
      the malate anions protect this sensitive growth zone by binding to Al(3+) in the
      apoplasm. We investigated the evolution of this trait in wheat, and demonstrated
      that it has multiple independent origins that enhance Al(3+) resistance by
      increasing TaALMT1 expression. One origin is likely to be Aegilops tauschii while
      other origins occurred more recently from a series of cis mutations that have
      generated tandemly repeated elements in the TaALMT1 promoter. We generated
      transgenic plants to directly compare these promoter alleles and demonstrate that
      the tandemly repeated elements act to enhance gene expression. This study
      provides an example from higher eukaryotes in which perfect tandem repeats are
      linked with transcriptional regulation and phenotypic change in the context of
      evolutionary adaptation to a major abiotic stress.

PMID- 20804459
TI  - Limited motor performance and minor neurological dysfunction at school age.
AB  - AIM: To investigate the relationship between motor performance and minor
      neurological dysfunction (MND) at school age. METHODS: Two hundred and fifty
      three children (158 boys, 95 girls; mean age 8 years and 7 months) of whom 167
      children received mainstream education and 86 children special education were
      neurologically examined according to Touwen. Special attention was paid to the
      severity of MND (simple or complex form) and type of dysfunction. Motor
      performance was assessed with the Movement Assessment Battery for Children
      (MABC), a parental questionnaire (Developmental Coordination Disorder
      Questionnaire; DCD-Q) and a teacher's questionnaire (Motor Observation
      Questionnaire for Teachers; MOQ-T). RESULTS: Total scores of MABC, DCD-Q and MOQ
      T were strongly related to the severity of MND and to dysfunctional coordination
      and fine manipulation. Mild dysfunction in posture and muscle tone was only
      weakly related to limited motor performance. Children with a MABC score < 5th
      percentile showed significantly more often complex MND than children with scores
      between the 5th and 15th percentile or >15th percentile (54% vs 17% and 10%).
      CONCLUSION: Limited motor performance is related to the severity and type of MND.
      Coordination problems and fine manipulative disability are strongly related to
      poor motor performance, mild dysfunctions of posture and muscle tone to a lesser
      extent.

PMID- 20804461
TI  - Neonatal pain assessment in Sweden - a fifteen-year follow up.
AB  - BACKGROUND: It has been proposed that a systematic pain assessment increases the
      awareness of the need to treat and prevent pain, and most international and
      national neonatal pain guidelines state that pain assessment should be performed
      in a systematic way. National surveys show a wide variation in compliance to
      these guidelines. METHODS: A survey to all Swedish neonatal units was performed
      in 1993, 1998, 2003 and 2008, concerning the use of, and need for, pain
      assessment tools. RESULTS: The number of units that tried to assess pain
      increased from 64% in 1993 to 83% in 2008. Forty-four per cent of these used a
      structured method in 2003, compared to three per cent in 1998. The most common
      pain indicator was facial actions. CONCLUSION: The proportion of neonatal units
      that reported the use of a structured pain assessment tool has increased
      significantly from 1993 to 2008. There is a need for better evidence for the
      relation between the implementation of pain guidelines and the actual performance
      of pain assessment.

PMID- 20804462
TI  - Cumulative responses of muscle protein synthesis are augmented with chronic
      resistance exercise training.
AB  - AIM: The purpose of this study was to determine the anabolic response of a single
      bout of high intensity resistance exercise (RE) following 5 weeks of RE training.
      METHODS: To complete these studies, Sprague-Dawley rats were assigned by body
      mass to RE, exercise control (EC), or sedentary cage control (CC) groups and
      studied over 36 h after 5 weeks of RE (squat-like) training. Cumulative (final 36
      h) fractional rates of muscle protein synthesis (FSR) were determined by 2H2O,
      and acute (16 h post-RE) rates of muscle protein synthesis (RPS) were determined
      by flooding with l-[2,3,4,5,6-3H]phenylalanine. Regulators of peptide-chain
      initiation, 4E-BP1, eIF4E and the association of the two were determined by
      Western blotting and immunoprecipitation respectively. RESULTS: No differences
      were observed with acute measures of RPS obtained 16 h following the final
      exercise bout in the plantaris or soleus muscles (P > 0.05). Consistent with this
      observation, 4E-BP1 was similarly phosphorylated and bound to eIF4E among all
      groups. However, upon determination of the cumulative response, FSR was
      significantly increased in the plantaris of RE vs. EC and CC (0.929+/-0.094,
      0.384+/-0.039, 0.300+/-0.022% h(-1) respectively; P<0.001), but not the soleus.
      CONCLUSION: With the advantage of determining cumulative FSR, the present study
      demonstrates that anabolic responses to RE are still evident after chronic RE
      training, primarily in muscle composed of fast-twitch fibres.

PMID- 20804463
TI  - Unaffected peak inspiratory flow through Turbuhaler during histamine inhalation
      challenge.

PMID- 20804464
TI  - Treatment with a Fel d 1 hypoallergen reduces allergic responses in a mouse model
      for cat allergy.
AB  - BACKGROUND:   A hypoallergen of the major cat allergen Fel d 1, recombinant (r)
      Fel d 1 (DTE III), was previously shown to have retained T-cell reactivity and
      strongly reduced IgE-binding capacity compared to unmodified rFel d 1. Here, we
      evaluated the therapeutic capacity of rFel d 1 (DTE III) in a mouse model for cat
      allergy. METHODS:   Mice were subcutaneously (s.c.) sensitized with rFel d 1 and
      subsequently treated (s.c.) with 50 or 200 MUg rFel d 1 (DTE III), or 50 MUg rFel
      d 1, prior to intranasal challenge with cat dander extract. Airway
      hyperreactivity (AHR), cells and cytokines in bronchoalveolar lavage fluid,
      splenocyte in vitro response, and serum immunoglobulins were analyzed. Seven cat
      allergic patients and ten healthy controls were tested for skin prick test (SPT)
      reactivity to rFel d 1 (DTE III) and rFel d 1. RESULTS:   Mice treated with 50
      and 200 MUg rFel d 1 (DTE III), and 50 MUg rFel d 1, produced increased serum
      levels of rFel d 1-specific IgG1 and IgG2a compared to sham-treated mice. IgG
      from all treatment groups could block binding of patients' IgE to rFel d 1. The
      200 MUg rFel d 1 (DTE III) treatment tended to reduce AHR. All mice tolerated
      treatment with rFel d 1 (DTE III), in contrast to only four of ten treated with
      rFel d 1. Compared to rFel d 1, the hypoallergen showed a tendency of reduced SPT
      reactivity. CONCLUSION:   The rFel d 1 (DTE III) hypoallergen might be a
      promising candidate for application in immunotherapy of cat allergy with improved
      safety and efficacy.

PMID- 20804465
TI  - Does allergic rhinitis exist in infancy? Findings from the PARIS birth cohort.
AB  - BACKGROUND:   Early onset of allergic rhinitis (AR) is poorly described, and
      rhinitis symptoms are often attributed to infections. This study analyses the
      relations between AR-like symptoms and atopy in infancy in the PARIS (Pollution
      and Asthma Risk: an Infant Study) birth cohort. METHODS:   Data on AR-like
      symptoms (runny nose, blocked nose, sneezing apart from a cold) were collected
      using a standardized questionnaire administered during the health examination at
      age 18 months included in the follow-up of the PARIS birth cohort. Parental
      history of allergy and children's atopy blood markers (blood eosinophilia >=470
      eosinophils/mm(3) , total immunoglobulin E >=45 U/ml and presence of allergen
      specific IgE) were assessed. Associations were studied using multivariate
      logistic regression models adjusted for potential confounders. RESULTS:  
      Prevalence of AR-like symptoms in the past year was 9.1% of the 1850 toddlers of
      the study cohort. AR-like symptoms and dry cough apart from a cold were frequent
      comorbid conditions. Parental history of AR in both parents increased the risk of
      suffering from AR-like symptoms with an OR 2.09 (P=0.036). Significant
      associations were found with the presence of concurrent biological markers of
      atopy, especially blood eosinophilia and sensitization to house dust mite (OR
      1.54, P=0.046 and OR 2.91, P=0.042) whereas there was no relation with
      sensitization to food. CONCLUSIONS:   These results support the hypothesis that
      AR could begin as early as 18 months of life. Suspicion of AR should be
      reinforced in infants with parental history of AR or biological evidence of
      atopy, particularly blood eosinophilia and sensitization to inhalant allergens.

PMID- 20804466
TI  - A case of severe anaphylaxis to kidney bean: phaseolin (vicilin) and PHA (lectin)
      identified as putative allergens.

PMID- 20804467
TI  - Indoor allergen levels in Guangzhou city, southern China.
AB  - BACKGROUND:   High levels of sensitization to house dust mites have been observed
      in Chinese allergic patients. This study has measured levels and distributions of
      mite and cockroach allergens in household dust in Guangzhou. Influences of home
      characteristics and seasonal changes on allergen levels were also investigated.
      METHODS:   Dust samples were collected from bedding and living room from
      households in Guangzhou. Major allergens from Dermatophagoides pteronyssinus, D.
      farinae, D. microceras, Blomia tropicalis and cockroach allergens were measured
      by ELISA. Home characteristics were obtained from a questionnaire. RESULTS:  
      Four hundred and four dust samples were collected from 107 homes during October
      2006 to November 2007. House dust mite allergen levels were detectable in 99% of
      the bedding samples. Der f 1 levels were significantly higher than Der p 1
      levels. High levels of mite allergens (>10 MUg/g) were observed in 88% of all the
      bedding samples. Cockroach allergens were detected in 93% of households and were
      higher in living room samples than in bedding samples. Blo t 5 and Der m 1 could
      not be detected in the dust samples. Having fabric furniture was a predictor of
      high allergen levels. Der f 1 levels were higher in summer time than in winter
      time. Cockroach allergens were higher in winter time than in summer time.
      CONCLUSION:   In Guangzhou, Der f 1 is the predominant mite allergen in dust with
      very high levels in bedding. Cockroach allergens are also common.

PMID- 20804468
TI  - Determinants of eczema: population-based cross-sectional study in Germany.
AB  - BACKGROUND:   Eczema is a chronic inflammatory skin disease and is among the most
      frequent chronic conditions in childhood and adolescence. It is the aim of this
      study to investigate determinants of eczema in German children and adolescents.
      METHODS:   Data were drawn from the public use files of the German Interview and
      Examination Survey for Children and Adolescents (KIGGS), a nationwide cross
      sectional representative survey conducted between 2003 and 2006, including 17,641
      children aged 0-17 (response rate: 66.6%). We investigated the association of a
      broad set of environmental and lifestyle exposures with ever physician-diagnosed
      eczema by means of univariable analyses and multivariable logistic regression
      modelling. RESULTS:   The weighted prevalence of ever physician-diagnosed eczema
      was 13.2% [95% confidence interval (CI) 12.5-13.9%]. In multivariable analysis,
      significant positive associations of parental allergies (OR 1.94, 95% CI 1.72
      2.19), parent-reported infection after birth (OR 1.45, 95% CI 1.05-2.00) and
      parent-reported jaundice after birth (OR 1.27, 95% CI 1.04-1.54) were revealed.
      Being a migrant (OR 0.63, 95% CI 0.49-0.80) and keeping a dog (OR 0.78, 95% CI
      0.64-0.96) showed significant inverse associations with eczema. Other lifestyle
      (alcohol consumption during pregnancy) and environmental factors (mould on the
      walls, pets, origin from East/West Germany) were not significantly related to
      eczema. CONCLUSIONS:   This study suggests that a family history of allergies is
      the strongest determinant of eczema. Perinatal health problems were associated
      with eczema, pointing to the importance of early life factors in the
      manifestation of eczema.

PMID- 20804469
TI  - Clinical monosensitivity to salmonid fish linked to specific IgE-epitopes on
      salmon and trout beta-parvalbumins.

PMID- 20804470
TI  - Mutational spectrum and phenotypes in Danish families with hereditary angioedema
      because of C1 inhibitor deficiency.
AB  - BACKGROUND: Hereditary angioedema (HAE), type I and II, is an autosomal dominant
      disease with deficiency of functional C1 inhibitor protein causing episodic
      swellings of skin, mucosa and viscera. HAE is a genetically heterogeneous disease
      with more than 200 different mutations in the SERPING1 gene. A genotype-phenotype
      relationship does not seem to exist in HAE, although the polymorphism c.-21T>C of
      exon 2 has been reported to be associated with a more severe phenotype. We aimed
      to establish the mutational spectrum of C1 inhibitor deficiency in Denmark and
      investigate the possible disease-aggravating effect of the c.-21T>C polymorphism.
      METHODS: Hereditary angioedema was diagnosed based on clinical features and C1
      inhibitor deficiency. A general severity score ranging from 0 to 10 was developed
      based on age at disease onset, clinical manifestations and treatment experiences.
      SERPING1 gene investigation was performed by exon sequencing followed by
      multiplex ligation-dependent probe amplification genomic rearrangement analysis
      in all known Danish HAE families. RESULTS: Fifty-nine patients with HAE from 26
      families were included in this study. The mean disease severity score was 7.12 [1
      10], and the mean C1 inhibitor function was 26% [20-46%]. The sensitivity of the
      mutational screening was 96%, and 13 new mutations were found in this Danish
      patient cohort. Nine patients (15%) carried the c.-21T>C polymorphism, but they
      didn't have a more severe phenotype. CONCLUSION: Thirteen new mutations were
      identified in the Danish HAE population. No correlation between the c.-21T>C
      polymorphism, the biochemical values of C1 inhibitor function and the clinical
      severity score was found.

PMID- 20804471
TI  - Clinical manifestations, co-sensitizations, and immunoblotting profiles of
      buckwheat-allergic patients.
AB  - BACKGROUND:   Buckwheat allergy is a rare food allergy in Europe and North
      America, whereas it is often described and studied in Asia. The aim of this study
      was to describe a series of patients with proven buckwheat allergy evaluated in
      an Italian allergy clinic. Co-sensitization to other food and inhalant allergens
      and immunoblotting profiles of buckwheat-allergic patients were studied. METHODS:
      Patients with suspected buckwheat allergy who attended the allergy clinic
      between January 1, 2006, and September 30, 2008, were evaluated. All patients
      underwent skin prick tests for a standard panel of inhalant and food allergens,
      prick-by-prick with buckwheat flour, buckwheat-specific IgE determinations, and
      double-blind placebo-controlled food challenge (DBPCFC) with buckwheat flour.
      Immunoblotting with buckwheat flour extract was performed on sera from buckwheat
      allergic patients. RESULTS:   Among 72 patients with suspected buckwheat allergy,
      30 (41.7%) were sensitized to buckwheat and 24 had a positive DBPCFC. The mean
      buckwheat IgE level was 6.23 kUA/l (range, 0.16 to >100 kUA/l). Several IgE
      binding proteins were identified and grouped into three patterns: a 16-kDa band
      in patients with predominantly gastrointestinal symptoms with grass and wheat
      flour co-sensitization, a 25-kDa band in patients with predominantly cutaneous
      symptoms and a low frequency of co-sensitization, and a 40-kDa band in patients
      with anaphylaxis and a low frequency of co-sensitization. CONCLUSIONS:  
      Buckwheat allergy is an emerging food allergy in Italy. We identified three
      distinct patterns of clinical and laboratory characteristics, suggesting that
      specific allergens could be more frequently associated with clinical
      manifestations of different severity.

PMID- 20804472
TI  - Prostate radiotherapy after radical prostatectomy: sooner or later?

PMID- 20804473
TI  - Application of simplified Fuhrman grading system in clear-cell renal cell
      carcinoma.
AB  - OBJECTIVE: To investigate the efficacy of simplified (two- or three-tiered)
      Fuhrman grading systems as prognostic indicators in clear-cell renal cell
      carcinoma (RCC). PATIENTS AND METHODS: By reviewing records, various
      clinicopathological factors were assessed in 431 patients who received surgical
      management for clear-cell RCC. A conventional four-tiered Fuhrman grading system
      was compared with a modified two-tiered grading system (Fuhrman grades I and II
      were combined as one class, and grades III and IV as another) and also with a
      three-tiered grading system (only grades I and II were combined). Efficacies of
      grading systems were assessed via univariate analyses and multivariate models for
      prediction of cancer-specific survival. RESULTS: In univariate analysis, the four
      tiered and three-tiered grading systems showed similar accuracies (76.5 vs 76.2%,
      P =0.614) for predicting cancer-specific survival, which were greater than that
      of the two-tiered system (72.5%; both P < 0.05). Of the three grading systems,
      only the three-tiered system was an independent predictor of cancer-specific
      survival in multivariate analysis (P = 0.046). When receiver operating
      characteristic-derived areas under the curve (AUCs) of multivariate models for
      predicting cancer-specific survivals were assessed, AUCs for models including the
      three-tiered Fuhrman grading system and the conventional four-tiered Fuhrman
      grading system were the same (95.3%), followed by that of a model incorporating
      the two-tiered grading system (95.1%). CONCLUSION: A modified, three-tiered
      Fuhrman grading system can be considered an appropriate option in the application
      of a nuclear grading system to the prognostication of clear-cell RCC in both
      univariate analysis and multivariate model setting.

PMID- 20804474
TI  - Bleeding after holmium laser enucleation of the prostate: lessons learned the
      hard way.
AB  - OBJECTIVE: To examine specific causes of postoperative bleeding requiring
      transfusion after holmium laser enucleation of the prostate (HoLEP) in order to
      enhance preoperative screening and counseling. MATERIALS AND METHODS: After
      Institutional Review Board (IRB) approval, a retrospective review of a single
      surgeon's experience of 130 consecutive HoLEPs was performed to specifically
      examine patients requiring perioperative blood transfusions. All patients from
      August 2007 to April 2009 who underwent a HoLEP at our institution since its
      inception were included. These patients' charts were reviewed to gain insight
      into their bleeding diathesis. A case series report was compiled and compared
      with the relevant published literature. RESULTS: Of the 130 patients, eight
      (6.7%) were found to require transfusion postoperatively. Four of these patients
      required a second operation for completion. These patients had a variety of
      causes for increased bleeding and subsequent transfusion including: chronic
      anticoagulation (n = 1), significant cardiac disease requiring maintenance of
      hemoglobin (n = 4), sepsis with secondary disseminated intravascular coagulation
      (n = 1), large prostate size (>150 g) (n = 4), underlying prostate cancer (n = 1)
      and inadequate anesthesia during the procedure leading to patient movement (n =
      1). All patients made a full recovery with satisfactory urinary symptom
      improvement except for one patient with residual incontinence at last follow-up.
      CONCLUSIONS: Despite the many benefits of holmium laser enucleation, all patients
      should be counseled regarding the real potential for postoperative blood
      transfusion. When feasible, any known bleeding risk should be minimized by the
      surgeon as long it is done safely for the benefit of the patient considering
      their co-morbidities.

PMID- 20804475
TI  - Endorectal magnetic resonance imaging has limited clinical ability to
      preoperatively predict pT3 prostate cancer.
AB  - OBJECTIVE: * To assess the clinical value of preoperative knowledge of the
      presence of extracapsular extension (ECE) or seminal vesicle invasion (SVI) in
      the planning for prostatectomy. MATERIALS AND METHODS: * An institutional
      database of 1161 robotic-assisted laparoscopic prostatectomies (RALP) performed
      by a single surgeon (D.B.S.) was queried for those who underwent endorectal coil
      magnetic resonance imaging (erMRI) before robotic-assisted laparoscopic
      prostatectomy. * erMRI reports were dichotomized into positive or negative and
      compared with the final histopathology. The erMRIs performed at academic centres
      were compared with those performed in non-academic settings. * A sub-group of
      high-risk patients was also analyzed for erMRI accuracy. RESULTS: * The 179
      patients who underwent erMRI had significantly worse disease compared to the 982
      patients without imaging. Of the 110 patients with histopathologically organ
      confined disease, 81 (74%) were correctly diagnosed as such on erMRI, whereas 29
      (26%) were felt to have cT3 disease and constituted false-positives. Among the 69
      patients with pT3 disease, erMRI correctly predicted 30 (43%), whereas 39 (57%)
      were incorrectly considered organ-confined. * The overall sensitivity and
      specificity for diagnosing pT3 disease was 43% and 73%. * When stratified by pT3a
      and pT3b, the sensitivity and specificity of erMRI to accurately diagnose ECE is
      33% and 81%, respectively. In evaluating SVI, erMRI has a sensitivity and
      specificity of 33% and 89%, respectively. The positive predictive value of erMRI
      to assess for ECE and SVI is 50% in both, with a negative predictive value of 61%
      and 63%, respectively. * erMRIs performed at academic centres compared to non
      academic locations demonstrated similar rates of sensitivity at 67% vs 77% and
      specificity at 39% vs 54%, respectively (P = 0.33). CONCLUSIONS: * In the setting
      of the present study, which was designed to be more reflective of current
      practice patterns in the USA, erMRI has limited clinical value in preoperatively
      detecting ECE and SVI. * The accuracy of detecting T3 disease did not improve in
      academic centres or in high-risk patients.

PMID- 20804476
TI  - Statin use and decreased risk of benign prostatic enlargement and lower urinary
      tract symptoms.
AB  - OBJECTIVE: To determine whether statin use is associated with a decreased risk of
      developing benign prostatic enlargement (BPE) and lower urinary tract symptoms
      (LUTS). SUBJECTS AND METHODS: We conducted a retrospective, population-based
      cohort study of 2447 men, 40-79 years of age, residing in Olmsted County, MN,
      USA, in 1990, and followed these men biennially through 2007. Cox proportional
      hazard models were used to assess associations between statin use and new onset
      of moderate/severe LUTS (American Urological Association Symptom Index score >7),
      a decreased maximum urinary flow rate (<12 mL/s) or BPE (prostate volume >30 mL).
      RESULTS: Statin use was inversely associated with new onset of LUTS (Hazard ratio
      (HR) 0.39; 95% confidence interval (CI) 0.31-0.49), a decreased maximum flow rate
      (HR 0.53; 95% CI 0.34-0.82) and BPE (HR 0.40; 95% CI 0.23-0.69) after adjustment
      for baseline age and body mass index, diabetes, hypertension, coronary heart
      disease, smoking, alcohol use, activity level and non-steroidal anti-inflammatory
      use. The longest duration of statin use was associated with the lowest risk of
      developing each outcome (all tests for trend: P < 0.001). CONCLUSION: In this
      study, statin use was associated with a 6.5- to 7-year delay in the new onset of
      moderate/severe LUTS or BPE. While men typically take statin medications to
      prevent coronary heart disease events and related outcomes, these data suggest
      that men who use statins may also receive urologic benefits.

PMID- 20804477
TI  - Correlation between expression of alpha1-adrenoceptor subtype mRNA and severity
      of lower urinary tract symptoms or bladder outlet obstruction in benign prostatic
      hyperplasia patients.
AB  - OBJECTIVE: To examine whether the direct correlation between the expression of
      alpha1-adrenoceptor (AR) subtype mRNA and severity of lower urinary tract
      symptoms (LUTS) or bladder outlet obstruction (BOO) in the prostate exists in
      benign prostatic hyperplasia (BPH) patients. PATIENTS AND METHODS: Sixty-eight
      patients with LUTS and BOO secondary to BPH were enrolled. Four prostate needle
      biopsy specimens were obtained from the transition zone to examine the expression
      level of alpha1-AR subtypes by Taqman reverse-transcription polymerase chain
      reaction. The correlation and regression between each expression level of alpha1
      AR subtype and clinical findings such as patient age, prostate volume,
      International Prostate Symptom Score (IPSS), quality of life (QOL) index, maximum
      flow rate in uroflowmetry (Qmax) and post-void residual urine volume (PVR) were
      assessed by stepwise multiple regression analysis. The correlation and regression
      between this expression level and individual symptoms of IPSS were assessed by
      Pearson's correlation coefficient and multiple regression analyses. RESULTS:
      Stepwise multiple regression analysis showed that the expression levels of
      alpha(1a) -AR, alpha(1b) -AR, alpha(1d) -AR and total alpha(1) -AR mRNA showed a
      significant regression with patient age, but not with prostate volume, IPSS, QOL
      index, Qmax and PVR. Pearson's correlation coefficient and multiple regression
      analyses demonstrated no correlation and regression between each alpha(1) -AR
      subtype mRNA expression level and individual symptoms of IPSS. CONCLUSIONS: There
      was no direct correlation between the expression of alpha1-AR subtype mRNA in the
      prostate and severity of LUTS or BOO in BPH patients, although the significant
      regression of this expression with patient age existed. LUTS and BOO may be
      associated with multiple factors and several other conditions may contribute to
      LUTS and BOO.

PMID- 20804478
TI  - Surgical management after active surveillance  for low-risk prostate cancer:
      pathological  outcomes compared with men undergoing  immediate treatment.
AB  - Study Type--Therapy (case control) Level of Evidence 3b. What's known on the
      subject? and What does the study add? The risks of delayed radical prostatectomy
      for men who progress on active surveillance are largely unknown. Two series have
      reported that prostatectomy after active surveillance has similar results to
      immediate therapy. Our data add to this growing body of evidence that
      appropriately selected men with prostate cancer can undergo active surveillance
      with delayed prostatectomy without added risk of missing an opportunity for cure
      as the majority of tumours remain organ confined. OBJECTIVE: * To compare the
      pathological outcomes of men undergoing radical prostatectomy (RP) after a period
      of active surveillance (AS) with those of a similar risk group undergoing
      immediate surgery. PATIENTS AND METHODS: * We identified men through our
      institutional database who underwent RP within 6 months of diagnosis or after a
      period of AS. The primary outcome of the present study was Gleason upgrade to >=7
      after prostatectomy. * Pathological stage and positive surgical margin rate were
      assessed as secondary outcomes. Binomial logistic regression models were used to
      determine associations of treatment subgroups with pathological upgrade, upstage
      and positive margins. RESULTS: * Thirty-three men with initially low-risk cancer
      features underwent RP after a median (range) of 18 (7-76) months of AS. A total
      of 278 men with low-risk disease features underwent immediate RP within 6 months
      of diagnosis. Rates of Gleason upgrading to >=7, pathological category pT3 and
      positive surgical margins did not differ significantly from the immediate RP
      group. * On multivariate analysis of low-risk patients, adjusting for baseline
      pathological features, treatment group (AS followed by prostatectomy vs immediate
      prostatectomy) was not associated with Gleason upgrading (odds ratio, OR, 0.35;
      95% CI, 0.12-1.04), non-organ-confined disease (OR, 1.67; 95% CI, 0.32-8.65) or
      positive surgical margins at prostatectomy (OR, 0.95; 95% CI, 0.16-5.76).
      CONCLUSION: * The present analysis did not show an association between RP after a
      period of AS and adverse pathological features for men with low-risk disease.

PMID- 20804479
TI  - Urinary nerve growth factor in women with overactive bladder syndrome.
AB  - OBJECTIVE: * To measure urinary nerve growth factor (NGF) in women with
      overactive bladder (OAB)-dry and OAB-wet and investigate the association of
      urinary NGF expression with these factors. PATIENTS AND METHODS: *
      Differentiation between OAB-wet and OAB-dry was based on symptoms and a 3-day
      voiding diary. * Urinary NGF levels were measured by enzyme-linked immunosorbent
      assay (ELISA). * The urinary NGF levels were compared among controls, OAB-dry and
      OAB-wet subgroups, and also between OAB patients >= 55 years and < 55 years, as
      well as between patients with a body mass index (BMI, kg/m2) < 20, 20-30 and >
      30. RESULTS: * A total of 113 women with OAB-dry, 106 with OAB-wet and 84
      controls were enrolled. The urinary NGF/creatinine (Cr) levels were significantly
      highest in OAB-wet (2.13 +/- 3.87) and second highest in OAB-dry (0.265 +/- 0.59)
      compared to controls (0.07 +/- 0.21). * Analysis of urinary NGF or NGF/Cr levels
      among controls, OAB-dry and OAB-wet groups by age and BMI showed no significant
      differences, except for the OAB-dry group. * Urinary NGF/Cr was not significantly
      correlated with age (P = 0.088) or BMI (P = 0.886) in women with OAB-dry and OAB
      wet. CONCLUSIONS: * Urinary NGF levels were significantly higher in women with
      OAB-dry and even higher in women with OAB-wet. * The urinary NGF level was not
      associated with ageing, menopause or higher BMI either in controls or OAB
      patients.

PMID- 20804480
TI  - Inhibition of fatty acid amide hydrolase suppresses referred hyperalgesia induced
      by bladder inflammation.
AB  - OBJECTIVE: * To determine (i) the presence of fatty acid amide hydrolase (FAAH)
      in the urinary bladder; (ii) whether or not endogenous fatty acid ethanolamides
      are synthesized by the bladder; (iii) the effects of FAAH inhibition on referred
      hyperalgesia associated with acute bladder inflammation in rats. MATERIALS AND
      METHODS: * Immunohistochemistry and immunoblotting were performed to detect FAAH
      in the bladder. Acrolein (1 mM, 400 uL) was instilled into bladders of female
      Wistar rats to induce cystitis. Referred mechanical hyperalgesia was assessed by
      application of Von Frey monofilaments to the hind paws. * Animals were killed 4,
      24, 48 and 72 h after acrolein instillation, and the fatty acid ethanolamide
      content of bladders was measured using isotope-dilution liquid
      chromatography/mass spectrometry. * Other rats were treated with the FAAH
      inhibitor URB597 (0.3 mg/kg, i.p.) after the induction of cystitis, and the
      mechanical sensitivity of the hind paws was determined. RESULTS: *
      Immunohistochemistry and immunoblotting showed the presence of FAAH in the
      bladder, with greatest abundance in the urothelium. * Acrolein-induced cystitis
      increased fatty acid ethanolamide content (including anandamide) in the bladder
      in a time-dependent manner. Inhibition of FAAH diminished referred hyperalgesia
      associated with acute bladder inflammation. CONCLUSIONS: * The results obtained
      in the present study indicate that (i) FAAH is present in the urinary bladder;
      (ii) fatty acid ethanolamides are increased during bladder inflammation; (iii)
      inhibition of FAAH could be an effective therapeutic approach for the treatment
      of bladder pain. * These results raise the possibility that inhibitors of enzymes
      responsible for metabolism of fatty acid ethanolamides could inhibit pain
      associated with bladder inflammation.

PMID- 20804481
TI  - Analysis of nocturia with 24-h urine volume, nocturnal urine volume, nocturnal
      bladder capacity and length of sleep duration: concept for effective treatment
      modality.
AB  - OBJECTIVE: * To determine the relationship between the number of nocturia and 24
      h urine volume, nocturnal urine volume, nocturnal bladder capacity and length of
      sleep duration as well as to assess the significance of these factors with
      respect to eliminating nocturnal voidings in individual patients with nocturia.
      PATIENTS AND METHODS: * Among 532 participants who completed a 3-day bladder
      diary between April 2005 and December 2006, the diaries of 450 participants
      without 24-h polyuria were analyzed. * Clinical variables such as the number of
      daytime and night-time voids, 24-h urine volume, nocturnal polyuria index,
      daytime and night-time maximum voided volumes (MVV), night/day MVV ratio, sleep
      duration and proportion of night/day urine production rates were obtained from
      each diary. * Participants were classified into eight groups according to values
      of three factors: nocturnal MVV, proportion of night/day urine production rates
      and length of sleep duration. * Each group was divided into three subgroups: non
      nocturics (number of nocturnal voidings is zero), mild nocturics (number of
      nocturnal voidings is one) and severe nocturics (number of nocturnal voidings is
      two or more). * The data from non-nocturics with three normal factors were
      regarded as the normal control and compared with the variables of the other
      subgroups using Dunnett's method. RESULTS: * Variables that form the basis of
      classifying participants into eight groups and corresponding to abnormal factors
      of each group were statistically significant in all the subgroups of each group.
      * Furthermore, a significantly increased 24-h urine volume was found in severe
      nocturics of the group with three normal factors. * A significantly decreased 24
      h urine volume was found in non-nocturics of groups with nocturnal polyuria,
      decreased bladder capacity and both long sleep duration and nocturnal polyuria. *
      A significantly increased nocturnal MVV and night/day MVV ratio were shown in non
      nocturics and mild nocturics of the groups with nocturnal polyuria and both long
      sleep duration and nocturnal polyuria. CONCLUSIONS: * Because nocturia is a
      multifactorial disorder and closely related to four factors (i.e. 24-h urine
      volume, nocturnal urine volume, nocturnal bladder capacity and length of sleep
      duration), the evaluation of all these factors appears to be clinically useful
      for determining the main contributing factor in patients with nocturia as well as
      the suitable treatment modality on an individual basis. * Physicians should take
      all these factors into consideration in the evaluation and treatment of nocturia.

PMID- 20804482
TI  - Five year expanded prostate cancer index composite-based quality of life outcomes
      after prostatectomy for localized prostate cancer.
AB  - OBJECTIVE: To document the Expanded Prostate cancer Index Composite (EPIC)
      results for men followed for 5 years after radical prostatectomy. PATIENTS AND
      METHODS: EPIC and demographic information were prospectively obtained from 434
      patients who received questionnaires preoperatively and 1, 4, 12, 24, 36, 48 and
      60 months postoperatively. Paired t-tests compared scores at individual time
      points. Percentage return to baseline was calculated at all postoperative time
      points and multivariate analyses evaluated postoperative trends. RESULTS: The
      mean age of patients was 63.4 years. Mean urinary function and incontinence
      worsen after prostatectomy, with recovery stable 12 months after surgery. Mean
      urinary bother returned to baseline by 4 months post-prostatectomy. Some 55.8%
      and 77.5% of patients return to their urinary function and bother baselines,
      respectively, 1 year after surgery. Mean sexual function and bother both declined
      after surgery, with new stable baselines achieved by 24 and 36 months post
      prostatectomy, respectively. Of the patients, 24.2% returned to their sexual
      function baseline by 24 months. No postoperative improvement was noted in mean
      sexual bother until the 12 months post-prostatectomy. Of the patients, 36.8%
      returned to their sexual bother baseline by 36 months. Minimal change was noted
      in the bowel and hormonal domains. CONCLUSIONS: Mean urinary function and
      incontinence did not recover to preoperative baseline after prostatectomy,
      although it did not add distress because mean urinary bother returned to pre
      prostatectomy levels. Mean sexual function declined post-prostatectomy, with
      continued recovery up to 24 months. Sexual bother recovered later but, once it
      reached a new baseline, the distress does not lessen with time, probably
      indicating an inability to adjust to their functional loss.

PMID- 20804483
TI  - Predictors of health-related quality of life recovery following laparoscopic
      simple, radical and donor nephrectomy.
AB  - OBJECTIVES: To objectively quantify the recovery of health-related quality of
      life (HRQL) in patients undergoing laparoscopic nephrectomy. To determine which
      factors are predictive of a more expedited recovery. MATERIALS AND METHODS:
      Patient recovery was prospectively measured among patients undergoing
      laparoscopic simple (n= 12), radical (n= 42) and donor (n= 95) nephrectomy. All
      procedures were performed using a 3- or 4-trocar, transperitoneal fully
      laparoscopic technique with intact specimen extraction using impermeable sacs for
      simple and radical nephrectomy, and hand extraction for donor nephrectomy.
      Postoperative recovery and quality of life were measured using the Postoperative
      Recovery Scale (PRS) administered preoperatively, immediately postoperatively and
      as an outpatient at 4, 8, 12, and 16 weeks postoperatively. ANOVA and Pearson's
      chi2 tests were performed on demographic data. Multivariate logistic regression
      analysis was used to calculate odds ratios for factors predictive of recovery.
      RESULTS: Statistically significant differences were found at baseline for age (P
      = 0.02), gender (P < 0.01), body mass index (BMI; P = 0.03), surgical side (P <
      0.01) and activity-based lifestyle (P = 0.04) across the three groups. Minimal
      adverse events were seen. Factors predictive of expedited recovery include age <
      50 years (OR: 2.1, P < 0.01), body-mass index (BMI) < 30 kg/m2 (OR: 1.7, P <
      0.01), active lifestyles (OR: 1.3, P < 0.01) and those patients undergoing
      nephrectomy for benign or malignant indications rather than for organ donation
      (OR: 1.4, P < 0.01). There was a significant delay in the donor group vs the non
      donor group with respect to the median number of days both groups took to recover
      75% and 90% of their baseline PRS scores (11 days, P = 0.02; 20 days, P = 0.02,
      respectively). CONCLUSIONS: Predictive factors of recovery from laparoscopic
      nephrectomy include age, BMI, lifestyle and surgical indication. Differences
      between HRQL recovery following donor vs non-donor laparoscopic nephrectomy are
      significant, and suggest the possible interplay of underlying psychological
      factors.

PMID- 20804484
TI  - Tunica-sparing ossified Peyronie's plaque excision.
AB  - OBJECTIVE: Ossified Peyronie's plaques may require surgical excision because of
      the palpable problems and penile curvature that result. As tunical excision can
      result in impotence and decrease penile sensation, we describe a novel method of
      tunical preserving excision of such lesions. PATIENTS AND METHODS: We evaluated
      12 men with dorsal penile curvature between 10 degrees  and 90 degrees . Penile
      plaque size ranged from 1 to 5 cm. 80% had painful erections. An artificial
      erection was induced with intracavernous injection of papaverine to assess penile
      deformity. Via a circumcising or ventral incision, plication sutures were placed
      to correct penile curvature. A lateral longitudinal corporotomy was made and the
      calcified/ossified portion was dissected free from the tunica albuginea/plaque of
      the corpora cavernosa. Watertight tunical closure was then performed. RESULTS:
      Postoperatively, 80% of men reported erections always adequate for intercourse
      and normal sensation with a mean follow-up of 7 months (range 2.1-14.5 months).
      All patients required simultaneous penile plication to ensure a straight phallus.
      Pathologic evaluation of plaque specimens all showed bone fragments. CONCLUSION:
      Tunica-sparing excision of the ossified/calcified portion of Peyronie's plaques
      shows a durable benefit for large, ossified lesions and maintains potency and
      penile sensation.

PMID- 20804485
TI  - Transurethral incision of congenital obstructive  lesions in the posterior
      urethra in boys and  its effect on urinary incontinence and  urodynamic study.
AB  - Study Type--Therapy (case series) Level of Evidence 4. What's known on the
      subject? and What does the study add? We have clarified that there exist two
      types of voiding urodynamics (pressure-flow-study) for congenital urethral
      obstruction in boys; one is synergic pattern (SP) and the other is dyssynergic
      pattern (DP). In terms of daytime incontinence and nocturnal enuresis, the
      transurethral endoscopic incision of these obstructive lesions is only effective
      in the SP type, while never effective in the DP type. The synergic pattern (SP)
      seems to represent simple anatomical obstruction, while the dyssynergic pattern
      (DP) may represent anatomical obstruction complicated with functional
      obstruction. The efficacy of endoscopic incision to mild forms of congenital
      urethral obstruction has been controversial, especially in terms of nocturnal
      enuresis. One of the reasons for the controversy is due to the lack of pre-and
      post-operative urodynamic assessment with its linkage to symptomatic change. We
      have, for the first time in the world, systematically conducted voiding
      urodynamic study for those elusive lesions seen in enuretic boys. Conclusively,
      for simple mechanical obstruction (SP), we confirmed that some voiding urodynamic
      parameters improve after the endoscopic incision, parallel to symptomatic
      improvement, while in the rest (DP) endoscopic incision is never effective. The
      cause of this ineffectiveness seemed to be due to persistent functional
      obstruction having superimposed on mechanical obstruction. The result of the
      study urges us to be more keen to diagnose and treat the mild congenial urethral
      obstruction as well as the concomitant functional obstruction in boys with
      nocturnal enuresis. OBJECTIVE: * To evaluate the clinical significance of
      congenital obstructive lesions of the posterior urethra in boys with refractory
      primary nocturnal enuresis. PATIENTS AND METHODS: * VCUG was performed in 43
      consecutive boys who visited our department from April 2004 to April 2009 who
      were unresponsive to conservative treatment. 20 patients of the 43 patients,
      underwent TUI. VCUG and UDS were performed before and 3-4 months after TUI. * In
      UDS, the maximum flow rate (Qmax), maximum bladder capacity, and post-voiding
      residual urine volume were determined using uroflowmetry (UFM), and the detrusor
      pressure (Pdet) at Qmax was determined in a pressure flow study (PFS). * Clinical
      outcome was evaluated 3-4 months and 6 months after TUI. RESULTS: * In VCUG
      performed 3-4 months after TUI, improvement was observed in urethral morphology
      in all patients. In preoperative PFS, two patterns were observed: 13 patients
      (65%) had a synergic pattern (SP) in which the Pdet increased with increasing
      urinary flow rate simultaneously with the initiation of voiding and seven (35%)
      had a dyssynergic pattern (DP) in which the Pdet was not coincident with the
      initiation of voiding, but was higher immediately before voiding than at Qmax.
      TUI was effective only in the SP group: symptomatic improvement was observed in
      87.5% of patients with daytime incontinence and 77% of patients with nocturnal
      enuresis 6 months after TUI. * In the DP group, no effect was observed (0%). With
      regard to changes in UDS parameters, a significant decrease (P= 0.0004) was
      observed in the Pdet at Qmax and a significant increase (P= 0.036) was observed
      in the maximum bladder capacity in the SP group, whereas no significant
      differences were noted in any parameters in the DP group. CONCLUSION: * Two
      voiding urodynamic patterns with different clinical outcomes of TUI were detected
      among patients with congenital posterior urethral obstruction, the underlying
      disease of refractory primary nocturnal enuresis in boys.

PMID- 20804486
TI  - Influence of caspases 8 and 9 gene promoter polymorphism on prostate cancer
      susceptibility and early development of hormone refractory prostate cancer.
AB  - OBJECTIVE: To investigate, by genotyping CASP8 (-652 6N del/ins) and CASP9 (-1263
      A > G; -293 19N del/ins), whether inactivation of apoptosis by genetic
      polymorphism of caspases 8 and 9 play an integral role in the mechanism of cancer
      development. To investigate the role of these polymorphisms in susceptibility to
      early development of hormone refractory prostate cancer. PATIENTS AND METHODS:
      The study included 175 histologically confirmed cases of prostate cancer and 198
      age and ethnicity matched healthy controls. CASP9-1263 A > G polymorphism was
      genotyped using the polymerase chain reaction-restriction fragment length
      polymorphism method. CASP9-293 del/ins and CASP8-652 del/ins polymorphisms were
      genotyped and the deletion pattern analysed by polyacrylamide gel
      electrophoresis. RESULTS: Our results demonstrated that presence of CASP9-1263 G
      allele was associated with reduced risk for prostate cancer (odds ratio 0.6,
      95%CI 0.39-0.92, P= 0.02). Other variant CASP9 was not associated with prostate
      cancer risk. Coincidentally, the presence of CASP9-1263 G allele was associated
      with increased risk for progression of prostate cancer to bone metastasis (odds
      ratio -2.28, 95%CI 1.14-4.53, P= 0.02). CASP8-652 (+/-) genotype was associated
      with increased hazard for early development of hormone refractory prostate cancer
      (hazard ratio 2.44, 95%CI 1.2-5.85, P= 0.045). CONCLUSION: Our results support
      the hypothesis that variants of CASP9 may influence the susceptibility to
      prostate cancer and its progression to bone metastasis. CASP8 polymorphism may
      influence the progression of prostate cancer disease to a hormone refractory
      state.

PMID- 20804487
TI  - Age-related properties of the tumour vasculature in renal cell carcinoma.
AB  - OBJECTIVE: To assess whether ageing processes influence angiogenesis in renal
      cell carcinoma (RCC) we carried out a pilot study of vascular properties in a
      series of archival primary kidney tumours in patients of different ages. PATIENTS
      AND METHODS: A cohort of patients with RCC was identified restrospectively, with
      an age range of 35-84 years. Paraffin-embedded, formalin-fixed sections of
      surgical tumour specimens were stained for endothelial (CD31, von Willebrand
      factor [vWF]), pericyte (alpha smooth muscle actin [SMA]) and leucocytic (CD45)
      markers, as well as for proliferative (Ki67) and angiogenic activity (tumour
      endothelial markers [TEMs], delta-like 4 [Dll4], Dll1, endothelial nitric oxide
      synthase [eNOS]). Vascular properties were compared between patients above and
      below 65 years of age. RESULTS: Microvascular density (MVD) within capillary hot
      spots was generally higher in patients with non-metastatic clear-cell RCC (ccRCC;
      n = 21) than in those with metastatic RCC (mRCC; n= 9). Patients with ccRCC who
      were more than 65 years old showed significantly higher MVD than their younger (<
      65 years) counterparts. There were dividing (Ki67-positive) endothelial and mural
      cells in both small (< 20 um) capillary and large (> 20 um), pre-capillary
      vessels, suggesting the involvement of both angiogenic and
      remodelling/arteriogenic processes. Tumour endothelial markers (TEM1, TEM7,
      TEM8), Notch ligands (Dll1, Dll4), and other molecular characteristics (eNOS)
      were analysed. Age-related differences were observed in the frequency of pre
      capillary vessels expressing Dll1, which was significantly higher in tumours of
      younger patients (< 65 years), while eNOS was more prevalent among capillaries
      associated with ccRCC in older patients (>6 5 years). CONCLUSIONS: The results of
      the present study suggest that age influences the structural and molecular
      properties of the tumour vasculature in ccRCC. We postulate that vascular ageing
      could also be relevant in the context of anti-angiogenic therapy.

PMID- 20804488
TI  - Laparoendoscopic single-site pyeloplasty: a comparison with the standard
      laparoscopic technique.
AB  - OBJECTIVE: * To compare laparoendoscopic single-site (LESS) and standard
      laparoscopic pyeloplasty procedures with the aim of defining whether
      perioperative, recovery or health-related quality of life (HRQL) benefits exist
      for the LESS procedure. PATIENTS AND METHODS: * From November 2007 to August
      2008, sixteen patients underwent LESS pyeloplasty at a tertiary care referral
      centre. These patients were compared with a matched cohort of patients undergoing
      standard laparoscopic pyeloplasty. * Matching criteria included gender and age
      (within 10 years), as well as preoperative degree of obstruction (T(1/2) within
      15 min) and differential renal function (within 10% ipsilaterally) based on
      diuretic radionuclide scanning. Mean follow-up was 13 +/- 4 months for the LESS
      group and 17 +/- 3 months for the standard laparoscopic group. * LESS pyeloplasty
      procedures were all performed using a single-port device in the umbilicus and
      suturing was assisted with a 2-mm grasping instrument. Perioperative variables,
      successful relief of obstruction and HRQL measurements were compared between the
      two groups. RESULTS: * Except for a lower body mass index in the LESS group (23
      +/- 6 kg/m2 vs 30 +/- 7 kg/m2, P = 0.002), no difference was noted for
      perioperative variables between the two cohorts, including hospital stay and
      analgesic requirement. * No significant HRQL advantage was noted for either group
      based on a six-item non-validated questionnaire. * All patients in both groups
      experienced clinical resolution of their symptoms. A patient in the standard
      laparoscopy group and two patients in the LESS group had T(1/2) > 20 min (0.063%
      vs 0.125%, P= 1.00) on diuretic radionuclide scanning. * Limitations include the
      retrospective nature of the present study, as well as the relatively small study
      population and short follow-up. CONCLUSIONS: * No benefit was noted for LESS
      pyeloplasty over the standard laparoscopic procedure beyond aesthetic advantages.
      * Further comparisons are needed to determine whether these results are
      generalizable to other LESS procedures.

PMID- 20804489
TI  - Sterile adhesive tapes: 'reducing the tension' when operating alone.

PMID- 20804490
TI  - Long-term results of noncultured epidermal cellular grafting in vitiligo, halo
      naevi, piebaldism and naevus depigmentosus.
AB  - BACKGROUND: Several surgical techniques are available for the treatment of stable
      leucoderma. The use of noncultured epidermal cellular grafting was introduced in
      1992. Data on long-term follow-up regarding stability of the repigmented area,
      time to achieve the final repigmentation, colour matching, reaction to sun
      exposure and patient satisfaction with treatment have been reported only a few
      times previously. OBJECTIVES: To evaluate the long-term results of the
      noncultured epidermal cellular grafting technique in patients with different
      types of leucoderma, including segmental vitiligo (n = 33), generalized vitiligo
      (n = 33), mixed vitiligo (n = 6), halo naevi (n = 11), piebaldism (n = 3) and
      naevus depigmentosus (n = 1). METHODS: Patients were evaluated by examination and
      questionnaire in a retrospective setting after transplantation by autologous
      noncultured cellular grafting. Percentage of repigmentation was evaluated in 82
      patients using a digital imaging analysis system (mean follow-up 15 months). Long
      term results were evaluated by 54 patients using a questionnaire up to 7.7 years
      after treatment (mean 4 years). RESULTS: More than 75% repigmentation was
      achieved in 71% of patients. Best results were obtained in segmental vitiligo,
      halo naevi and piebaldism, whereas results in generalized or mixed vitiligo were
      inferior. According to the patients, final repigmentation was achieved after a
      mean of 10 months post-treatment. In 80% some colour mismatch (hyperpigmentation
      and hypopigmentation) was reported between the treated area and the surrounding
      skin, although this was not disturbing for the majority. This colour mismatch was
      reported significantly less after sun exposure (P = 0.012). During follow-up 7%
      of patients, all with generalized vitiligo, observed some loss of the achieved
      repigmentation. CONCLUSIONS: Autologous epidermal cellular grafting achieved a
      high percentage of repigmentation, which was maintained during follow-up in the
      majority of patients. Although it improved quality of life, a perfect colour
      match was seldom obtained.

PMID- 20804491
TI  - Induction of p38, tumour necrosis factor-alpha and RANTES by mechanical
      stretching of keratinocytes expressing mutant keratin 10R156H.
AB  - BACKGROUND: Epidermolytic hyperkeratosis (bullous congenital ichthyosiform
      erythroderma), characterized by ichthyotic, rippled hyperkeratosis, erythroderma
      and skin blistering, is a rare autosomal dominant disease caused by mutations in
      keratin 1 or keratin 10 (K10) genes. A severe phenotype is caused by a missense
      mutation in a highly conserved arginine residue at position 156 (R156) in K10.
      OBJECTIVES: To analyse molecular pathomechanisms of hyperproliferation and
      hyperkeratosis, we investigated the defects in mechanosensation and
      mechanotransduction in keratinocytes carrying the K10(R156H) mutation. METHODS:
      Differentiated primary human keratinocytes infected with lentiviral vectors
      carrying wild-type K10 (K10(wt)) or mutated K10(R156H) were subjected to 20%
      isoaxial stretch. Cellular fragility and mechanosensation were studied by
      analysis of mitogen-activated protein kinase activation and cytokine release.
      RESULTS: Cultured keratinocytes expressing K10(R156H) showed keratin aggregate
      formation at the cell periphery, whereas the filament network in K10(wt) cells
      was normal. Under stretching conditions K10(R156H) keratinocytes exhibited about
      a twofold higher level of filament collapse compared with steady state. In
      stretched K10(R156H) cells, higher p38 activation, higher release of tumour
      necrosis factor-alpha and RANTES but reduced interleukin-1beta secretion compared
      with K10(wt) cells was observed. CONCLUSIONS: These results demonstrate that the
      R156H mutation in K10 destabilizes the keratin intermediate filament network and
      affects stress signalling and inflammatory responses to mechanical stretch in
      differentiated cultured keratinocytes.

PMID- 20804492
TI  - Severe congenital lymphoedema not caused by mutations in known lymphoedema genes.

PMID- 20804493
TI  - Evidence for CGRP re-uptake in rat dura mater encephali.
AB  - BACKGROUND AND PURPOSE: Calcitonin gene-related peptide (CGRP) is widely
      distributed in the trigeminovascular system and released from sensory fibres of
      the cranial dura mater upon noxious stimulation. Such release may be a mechanism
      underlying migraine headache. Based on data from guinea pig basilar artery
      preparations, we have here studied CGRP release and uptake in an organ
      preparation of the hemisected rat skull. EXPERIMENTAL APPROACH: CGRP release from
      the cranial dura was quantified by a commercial enzyme-linked immunoassay. CGRP
      was depleted using repetitive challenges of capsaicin. After incubating the
      tissue with CGRP for 20 min and extensive washing, another capsaicin challenge
      was performed. Immunohistochemistry was used to visualize CGRP immunofluorescence
      in dural nerve fibres. KEY RESULTS: Capsaicin-induced CGRP release was attenuated
      by the transient receptor potential vanilloid receptor type I antagonist
      capsazepine or by Ca(2+)-free solutions. After the CGRP-depleted preparation had
      been exposed to exogenous CGRP, capsaicin-induced CGRP release was increased
      compared to the challenge just prior to incubation. CGRP uptake was not
      influenced by Ca(2+)-free solutions. Olcegepant and CGRP(8-37) (CGRP receptor
      antagonists) did not affect uptake of CGRP. However, a monoclonal CGRP-binding
      antibody decreased CGRP uptake significantly. Release of CGRP after incubation
      was attenuated by Ca(2+)-free solutions and by capsazepine. Immunohistochemical
      assays indicated a weak trend towards CGRP uptake in rat dura mater. CONCLUSION
      AND IMPLICATIONS: We have presented evidence for CGRP uptake in nerves and its re
      release in rat dura mater. This may have implications for the pathophysiology and
      treatment of migraine.

PMID- 20804494
TI  - cAMP inhibits modulation of airway smooth muscle phenotype via the exchange
      protein activated by cAMP (Epac) and protein kinase A.
AB  - BACKGROUND AND PURPOSE: Changes in airway smooth muscle (ASM) phenotype may
      contribute to the pathogenesis of airway disease. Platelet-derived growth factor
      (PDGF) switches ASM from a contractile to a proliferative, hypo-contractile
      phenotype, a process requiring activation of extracellular signal-regulated
      kinase (ERK) and p70(S6) Kinase (p70(S6K) ). The effects of cAMP-elevating agents
      on these processes is unknown. Here, we investigated the effects of cAMP
      elevation by prostaglandin E(2) (PGE(2) ) and the activation of the cAMP
      effectors, protein kinase A (PKA) and exchange protein activated by cAMP (Epac)
      on PDGF-induced phenotype switching in bovine tracheal smooth muscle (BTSM).
      EXPERIMENTAL APPROACH: Effects of long-term treatment with the PGE(2) analogue
      16,16-dimethyl-PGE(2) , the selective Epac activator, 8-pCPT-2'-O-Me-cAMP and the
      selective PKA activator, 6-Bnz-cAMP were assessed on the induction of a hypo
      contractile, proliferative BTSM phenotype and on activation of ERK and p70(S6K) ,
      both induced by PDGF. KEY RESULTS: Treatment with 16,16-dimethyl-PGE(2) inhibited
      PDGF-induced proliferation of BTSM cells and maintained BTSM strip contractility
      and contractile protein expression in the presence of PDGF. Activation of both
      Epac and PKA similarly prevented PDGF-induced phenotype switching and PDGF
      induced activation of ERK. Interestingly, only PKA activation resulted in
      inhibition of PDGF-induced phosphorylation of p70(S6K) . CONCLUSIONS AND
      IMPLICATIONS: Our data indicate for the first time that both Epac and PKA
      regulated switching of ASM phenotype via differential inhibition of ERK and
      p70(S6K) pathways. These findings suggest that cAMP elevation may be beneficial
      in the treatment of long-term changes in airway disease.

PMID- 20804495
TI  - Analysis of the actions of the novel dopamine receptor-directed compounds (S)
      OSU6162 and ACR16 at the D2 dopamine receptor.
AB  - BACKGROUND AND PURPOSE; The two phenylpiperidines, OSU6162 and ACR16, have been
      proposed as novel drugs for the treatment of brain disorders, including
      schizophrenia and Huntington's disease, because of their putative dopamine
      stabilizing effects. Here we evaluated the activities of these compounds in a
      range of assays for the D(2) dopamine receptor in vitro. EXPERIMENTAL APPROACH:
      The affinities of these compounds for the D(2) dopamine receptor were evaluated
      in competition with [(3) H]spiperone and [(3) H]NPA. Agonist activity of these
      compounds was evaluated in terms of their ability to stimulate [(35) S]GTPgammaS
      binding. KEY RESULTS: Both compounds had low affinities for inhibition of [(3)
      H]spiperone binding (pK(i) vs. [(3) H]spiperone, ACR16: <5, OSU6162: 5.36).
      Neither compound was able to stimulate [(35) S]GTPgammaS binding when assayed in
      the presence of Na(+) ions, but if the Na(+) ions were removed, both compounds
      were low-affinity, partial agonists (E(max) relative to dopamine: ACR16: 10.2%,
      OSU6162:54.3%). Schild analysis of the effects of OSU6162 to inhibit dopamine
      stimulated [(35) S]GTPgammaS binding indicated Schild slopes of ~0.9, suggesting
      little deviation from competitive inhibition. OSU6162 was, however, able to
      accelerate [(3) H]NPA dissociation from D(2) dopamine receptors, indicating some
      allosteric effects of this compound. CONCLUSIONS AND IMPLICATIONS: The two
      phenylpiperidines were low-affinity, low-efficacy partial agonists at the D(2)
      dopamine receptor in vitro, possibly exhibiting some allosteric effects.
      Comparing their in vitro and in vivo effects, the in vitro affinities were a
      reasonable guide to potencies in vivo. However, the lack of in vitro-in vivo
      correlation for agonist efficacy needs to be further addressed. LINKED ARTICLES:
      This article is part of a themed section on Analytical Receptor Pharmacology in
      Drug Discovery. To view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2010.161.issue-6.

PMID- 20804497
TI  - Blockade of tachykinin NK3 receptor reverses hypertension through a dopaminergic
      mechanism in the ventral tegmental area of spontaneously hypertensive rats.
AB  - BACKGROUND AND PURPOSE: Intracerebroventricularly injected tachykinin NK(3)
      receptor (R) antagonists normalize mean arterial blood pressure (MAP) in
      spontaneously hypertensive rats (SHR). This study was pursued to define the role
      played by NK(3)R located on dopamine neurones of the ventral tegmental area (VTA)
      in the regulation of MAP in SHR. EXPERIMENTAL APPROACH: SHR (16 weeks) were
      implanted permanently with i.c.v. and/or VTA guide cannulae. Experiments were
      conducted 24 h after catheterization of the abdominal aorta to measure MAP and
      heart rate (HR) in freely behaving rats. Cardiovascular responses to i.c.v. or
      VTA-injected NK(3)R agonist (senktide) and antagonists (SB222200 and R-820) were
      measured before and after systemic administration of selective antagonists for
      D(1)R (SCH23390), D(2)R (raclopride) or non-selective D(2)R (haloperidol), and
      after destruction of the VTA with ibotenic acid. KEY RESULTS: I.c.v. or VTA
      injected SB222200 and R-820 (500 pmol) evoked anti-hypertension, which was
      blocked by raclopride. Senktide (10, 25, 65 and 100 pmol) elicited greater
      increases of MAP and HR when injected in the VTA, and the cardiovascular response
      was blocked by R-820, SCH23390 and haloperidol. VTA-injected SB222200 prevented
      the pressor response to i.c.v. senktide, and vice versa, i.c.v. senktide
      prevented the anti-hypertension to VTA SB222200. Destruction of the VTA prevented
      the pressor response to i.c.v. senktide and the anti-hypertension to i.c.v. R
      820. CONCLUSIONS AND IMPLICATIONS: The NK(3)R in the VTA is implicated in the
      maintenance of hypertension by increasing midbrain dopaminergic transmission in
      SHR. Hence, this receptor may represent a therapeutic target in the treatment of
      hypertension.

PMID- 20804498
TI  - Pharmacokinetic analysis of pralidoxime after its intramuscular injection alone
      or in combination with atropine-avizafone in healthy volunteers.
AB  - BACKGROUND AND PURPOSE: Treatment of organophosphate poisoning with pralidoxime
      needs to be improved. Here we have studied the pharmacokinetics of pralidoxime
      after its intramuscular injection alone or in combination with avizafone and
      atropine using an auto-injector device. EXPERIMENTAL APPROACH: The study was
      conducted in an open, randomized, single-dose, two-way, cross-over design. At
      each period, each subject received either intramuscular injections of pralidoxime
      (700 mg), or two injections of the combination: pralidoxime (350 mg), atropine (2
      mg), avizafone (20 mg). Pralidoxime concentrations were quantified using a
      validated LC/MS-MS method. Two approaches were used to analyse these data: (i) a
      non-compartmental approach; and (ii) a compartmental modelling approach. KEY
      RESULTS: The injection of pralidoxime combination with atropine and avizafone
      provided a higher pralidoxime maximal concentration than that obtained after the
      injection of pralidoxime alone (out of bioequivalence range), while pralidoxime
      AUC values were equivalent. Pralidoxime concentrations reached their maximal
      value earlier after the injection of the combination. According to Akaike and to
      goodness of fit criteria, the best model describing the pharmacokinetics of
      pralidoxime was a two-compartment with a zero-order absorption model. When
      avizafone and atropine were injected with pralidoxime, the best model describing
      pralidoxime pharmacokinetics becomes a two-compartment with a first-order
      absorption model. CONCLUSIONS AND IMPLICATIONS: The two approaches, non
      compartmental and compartmental, showed that the administration of avizafone and
      atropine with pralidoxime results in a faster absorption into the general
      circulation and higher maximal concentrations, compared with the administration
      of pralidoxime alone.

PMID- 20804499
TI  - Immunotherapy targeting fibroblast activation protein inhibits tumor growth and
      increases survival in a murine colon cancer model.
AB  - Murine studies have shown that immunological targeting of fibroblast activation
      protein (FAP) can elicit protective immunity in the absence of significant
      pathology. Fibroblast activation protein is a product overexpressed by tumor
      associated fibroblasts (TAF) and is the predominant component of the stoma in
      most types of cancer. Tumor-associated fibroblasts differ from normal adult
      tissue fibroblasts, and instead resemble transient fetal and wound healing
      associated fibroblasts. Tumor-associated fibroblasts are critical regulators of
      tumorigenesis, but differ from tumor cells by being more genetically stable.
      Therefore, in comparison to tumor cells, TAF may represent more viable
      therapeutic targets for cancer immunotherapy. To specifically target TAF, we
      constructed a DNA vaccine directed against FAP. This vaccine significantly
      suppressed primary tumor and pulmonary metastases primarily through CD8(+) T-cell
      mediated killing in tumor-bearing mice. Most importantly, tumor-bearing mice
      vaccinated against FAP exhibited a 1.5-fold increase in lifespan and no
      significant pathology. These results suggest that FAP, a product preferentially
      expressed by TAF, could function as an effective tumor rejection antigen.

PMID- 20804496
TI  - TRP channels in neurogastroenterology: opportunities for therapeutic
      intervention.
AB  - The members of the superfamily of transient receptor potential (TRP) cation
      channels are involved in a plethora of cellular functions. During the last
      decade, a vast amount of evidence is accumulating that attributes an important
      role to these cation channels in different regulatory aspects of the alimentary
      tract. In this review we discuss the expression patterns and roles of TRP
      channels in the regulation of gastrointestinal motility, enteric nervous system
      signalling and visceral sensation, and provide our perspectives on
      pharmacological targeting of TRPs as a strategy to treat various gastrointestinal
      disorders. We found that the current knowledge about the role of some members of
      the TRP superfamily in neurogastroenterology is rather limited, whereas the
      function of other TRP channels, especially of those implicated in smooth muscle
      cell contractility (TRPC4, TRPC6), visceral sensitivity and hypersensitivity
      (TRPV1, TRPV4, TRPA1), tends to be well established. Compared with expression
      data, mechanistic information about TRP channels in intestinal pacemaking (TRPC4,
      TRPC6, TRPM7), enteric nervous system signalling (TRPCs) and enteroendocrine
      cells (TRPM5) is lacking. It is clear that several different TRP channels play
      important roles in the cellular apparatus that controls gastrointestinal
      function. They are involved in the regulation of gastrointestinal motility and
      absorption, visceral sensation and visceral hypersensitivity. TRP channels can be
      considered as interesting targets to tackle digestive diseases, motility
      disorders and visceral pain. At present, TRPV1 antagonists are under development
      for the treatment of heartburn and visceral hypersensitivity, but interference
      with other TRP channels is also tempting. However, their role in gastrointestinal
      pathophysiology first needs to be further elucidated.

PMID- 20804500
TI  - Inhibition of carcinoma cell motility by epoxyeicosatrienoic acid (EET)
      antagonists.
AB  - Cytochrome P450 (CYP) epoxygenases, CYP2C8, 2C9 and 2J2 mRNA and proteins, were
      expressed in prostate carcinoma (PC-3, DU-145 and LNCaP) cells. 11,12
      Epoxyeicosatrienoic acid (11,12-EET) was the major arachidonic acid metabolite in
      these cells. Blocking EET synthesis by a selective CYP epoxygenase inhibitor (N
      methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide [MS-PPOH]) inhibited tonic
      (basal) invasion and migration (motility) while exogenously added EET induced
      cell motility in a concentration-dependent manner. An epidermal growth factor
      receptor (EGFR) kinase inhibitor (AG494) or a PI3 kinase inhibitor (LY294002)
      inhibited cell migration and reduced 11,12-EET-induced cell migration.
      Importantly, synthetic EET antagonists (14,15-epoxyeicosa-5(Z)-enoic acid [14,15
      EEZE], 14,15-epoxyeicosa-5(Z)-enoic acid 2-[2-(3-hydroxy-propoxy)-ethoxy]-ethyl
      ester [14,15-EEZE-PEG] and 14,15-epoxyeicosa-5(Z)-enoic-methylsulfonylimide
      [14,15-EEZE-mSI]) inhibited EET-induced cell invasion and migration. 11,12-EET
      induced cell stretching and myosin-actin microfilament formation as well as
      increased phosphorylation of EGFR and Akt (Ser473), while 14,15-EEZE inhibited
      these effects. These results suggest that EET induce and EET antagonists inhibit
      cell motility, possibly by putative EET receptor-mediated EGFR and PI3K/Akt
      pathways, and suggest that EET antagonists are potential therapeutic agents for
      prostate cancer.

PMID- 20804501
TI  - Antitumor effects of combined granulocyte macrophage colony stimulating factor
      and macrophage inflammatory protein-3 alpha plasmid DNA.
AB  - Dendritic cells (DC) are critical for priming adaptive immune responses to
      foreign antigens. However, the feasibility of harnessing these cells in vivo to
      optimize the antitumor effects has not been fully explored. The authors
      investigated a novel therapeutic approach that involves delivering synergistic
      signals that both recruit and expand DC populations at sites of intratumoral
      injection. More specifically, the authors examined whether the co-administration
      of plasmids encoding the chemokine macrophage inflammatory protein-3 alpha
      (pMIP3alpha) and plasmid encoding the granulocyte macrophage colony stimulating
      factor (pGM-CSF; a DC-specific growth factor) can recruit, expand and activate
      large numbers of DC at sites of intratumoral injection. It was found that the
      administration of pGM-CSF and pMIP3alpha resulted in dramatic recruitment and
      expansion of DC at these sites and in draining lymph nodes. Furthermore,
      treatment with pGM-CSF and pMIP3alpha generated the strongest MUC1-associated
      CD8+ T-cell immune responses in draining lymph nodes and in tumors, produced the
      greatest antitumor effects and enhanced survival rates more than pcDNA3.1, pGM
      CSF alone and pMIP3alpha alone. It was also found that pGM-CSF plus pMIP3alpha
      generated the strongest MUC1-associated CD4+ T-cell immune responses in draining
      lymph nodes and in tumors. The findings of the present study suggest that the
      recruitment and activation of DC in vivo due to the synergistic actions of pGM
      CSF and pMIP3alpha presents a potentially feasible means of controlling
      immunogenic malignancies and provides a basis for the development of novel
      immunotherapeutic treatments.

PMID- 20804502
TI  - A set of genes associated with the interferon-gamma response of lung cancer
      patients undergoing alpha-galactosylceramide-pulsed dendritic cell therapy.
AB  - Invariant natural killer T (iNKT) cells possess potent antitumor effects after
      activation with a specific glycolipid antigen, alpha-galactosylceramide
      (alphaGalCer). A phase I-II clinical study of alphaGalCer-pulsed dendritic cells
      (DC) to activate endogenous iNKT cells was previously performed in patients with
      non-small-cell lung cancer (NSCLC). In this clinical trial, the patients with
      increased interferon-gamma (IFN-gamma) production (>two-fold) in PBMC after the
      DC treatment (good responder group) experienced a prolonged overall survival time
      in comparison with the poor responder group. We extended the previous study and
      performed a microarray-based gene expression analysis using peripheral blood
      CD56(+) cells and CD56(-) CD3(+) T cells from patients enrolled in the above
      mentioned clinical study. We sought to identify any biomarkers associated with
      the immune responses in this immunotherapy trial. Six patient samples
      corresponding to three subjects in the good responder group and three subjects in
      the poor responder group were included in the microarray analysis. Genes
      differentially expressed between pre-treatment and post-treatment samples were
      selected for analysis. Subsequently, genes that were only expressed in the good
      responder group or poor responder group were chosen. After these procedures, four
      selected genes were quantified by reverse transcriptase-polymerase chain reaction
      in another eight patient samples, and two genes, LTB4DH and DPYSL3, were
      confirmed to be candidate genes for the predictor of a good immune response. The
      expression profile of these two genes may be associated with the responsiveness
      of IFN-gamma production after alphaGalCer-pulsed DC treatment.

PMID- 20804503
TI  - Identification and characterization of cancer stem cells in ovarian yolk sac
      tumors.
AB  - Recent evidence supports the cancer stem cell theory, that is, that malignant
      tumors arise from cells termed cancer stem cells or tumor-initiating cells that
      have the ability to self-renew and are responsible for maintaining the tumor.
      Cells with marked tumor-initiating capacity have recently been identified in a
      number of solid tumors. CD133 (PROM1, human prominin-1) has been used as a marker
      to detect stem cells (progenitor cells) and cancer stem cells (tumor-initiating
      cells) in various tissues. Ovarian yolk sac tumors (YSTs) are rare and highly
      malignant. The present study was designed to evaluate the tumor-forming ability
      of CD133(+) cells in ovarian YST cell lines and to examine the characteristics of
      CD133(+) cells, such as cell growth and invasiveness. Our data suggest ovarian
      YST to be maintained by a rare fraction of cancer stem-like cells that express
      the cell surface marker CD133.

PMID- 20804504
TI  - Pincer nails associated with pamidronate.

PMID- 20804505
TI  - Versican targeting by RNA interference suppresses aggregative growth of dermal
      papilla cells.
AB  - BACKGROUND: Dermal papilla cells (DPCs) are specialized fibroblasts found in the
      hair follicle papilla, which are associated with the development and cycle
      regulation of hair follicles (HFs). DPCs exhibit a multilayer aggregative growth
      character, which is closely related to induction of HF formation. Versican, a
      large chondroitin sulphate proteoglycan and one of the major components of the
      extracellular matrix, is involved in the formation of HF. METHODS: To confirm the
      relationship between versican and the aggregative growth of DPCs, we first
      induced and established an aggregative cell model in DPCs in vitro, with cells
      taken to passage 8. Simultaneously, aggregative passage 2 DPCs and nonaggregative
      passage 8 DPCs were selected as parallel controls. RNA interference (RNAi)
      targeted to versican was used in passage 2 DPCs using a lentiviral vector.
      Reverse transcriptase (RT)-PCR and western blotting were used to assay the
      expression of versican in DPCs. RESULTS: RNAi targeted to versican efficiently
      suppressed the aggregative growth of passage 2 DPCs, and the inhibitory effect
      was significant 3 days after RNAi treatment. The mRNA and protein levels of
      versican were also downregulated in passage 2 DPCs, and were lower than levels in
      nonaggregative passage 8 DPCs. Notably, the aggregative growth of nonaggregative
      passage 8 DPCs was restored after induction in a 1 : 1 v/v mixture of fresh DMEM
      and medium recycled from a previous passage. CONCLUSION: Versican is a key gene
      for the aggregative growth of DPCs, and might be significant in the regeneration
      of HF.

PMID- 20804506
TI  - Antioxidants add protection to a broad-spectrum sunscreen.
AB  - BACKGROUND: Exposure of human skin to ultraviolet radiation (UVR) results in
      erythema, pigment darkening, skin cancer and photoageing. In addition to
      conventional organochemical and the physical-mineral type sunscreens (SS), other
      non-SS protective strategies have been investigated, including antioxidants (AOx)
      and topical DNA repair enzymes. AIM: To investigate whether AOx could improve the
      protection provided by a broad-spectrum sunscreen (SS) preparation. METHODS:
      Volunteers were exposed to repetitive solar-simulated (ss)UVR at 1.5 times
      minimal erythema dose for four consecutive days. Thirty minutes before each
      exposure and 6, 24 and 48 h after the last exposure, the test materials [vehicle,
      SS (sun protection factor 25) alone, AOx alone and SS plus AOx] were applied to
      four different sites. Another two sites received ssUVR only, or SS plus AOx only,
      and a third site was left untreated (neither ssUVR or product). Erythema and
      pigmentation were measured using a Mexameter. Biopsy specimens were taken 72 h
      after the last irradiation. The thickness of the stratum corneum and epidermis
      were measured by microscopy. Expression of cytokeratins (CKs), matrix
      metalloproteinases (MMPs) and CD1a-positive Langerhans cells (LCs) analysed by
      immunohistochemical staining, and relative expression levels were compared
      between all seven sites. RESULTS: AOx alone did not reduce erythema. There was a
      significant reduction in pigmentation, and the product almost completely
      protected against LC depletion. AOx plus SS gave better protection against
      pigment formation and CK5/6 induction than SS alone. AOx alone protected against
      ssUVR-induced hyperproliferation, as shown by epidermal thickness and CK16
      biomarkers, and was better than SS alone. Interestingly, although protection
      against induction of MMP-9, a marker of photoageing, did not reach significance
      when either SS or AOx were applied separately, there was complete protection
      against MMP-9 induction when these were combined. CONCLUSIONS: Non-SS materials
      such as AOx can contribute significantly to sun protection when added to a broad
      spectrum SS and applied topically to human skin in vivo.

PMID- 20804507
TI  - Isotretinoin does not induce insulin resistance in patients with acne.
AB  - BACKGROUND: Isotretinoin treatment causes hypertriglyceridaemia. Insulin
      resistance is also associated with hypertriglyceridaemia. It is not known if
      isotretinoin is related to insulin resistance. AIM: To test this hypothesis, we
      measured insulin resistance in 48 patients with acne vulgaris (AV) before and
      after 3 months of isotretinoin treatment. METHODS: In total, 48 patients with AV
      who attended the dermatology outpatient clinic at Kecioren Research and Training
      Hospital were included. Screening for biochemical parameters was performed just
      before the start of treatment (pretreatment) and after 4 months of isotretinoin
      therapy (post-treatment). The parameters measured were insulin, C peptide,
      fasting blood glucose, aspartate and alanine aminotransferases (AST, ALT), total
      cholesterol (TC), triglyceride, high-density lipoprotein cholesterol (HDL-C), low
      density lipoprotein (LDL-C) and very low-density lipoprotein cholesterol. Insulin
      resistance was measured using the Homeostasis Model Assessment of Insulin
      Resistance (HOMA-IR) method. RESULTS: Compared with initial values, AST, ALT, TC,
      LDL-C and triglyceride levels were significantly increased (P < 0.01, < 0.05, <
      0.01, < 0.05 and < 0.01, respectively), but there was no significant change in
      fasting blood glucose, insulin, C-peptide levels or HOMA-IR. CONCLUSIONS: Three
      months of isotretinoin treatment did not change insulin sensitivity in patients
      with AV. Further studies with insulin resistance models may even reveal an
      improvement in insulin resistance, as experimental animal studies have previously
      shown.

PMID- 20804508
TI  - Serum neopterin levels in spontaneous urticaria and atopic dermatitis.
AB  - Serum neopterin may be considered a diagnostic marker of the degree of activation
      of the immune system. This preliminary study was performed to measure serum
      neopterin levels in patients with acute spontaneous urticaria (ASU), chronic
      spontaneous urticaria (CSU) and atopic dermatitis (AD). In total, 180 patients
      [96 men, 84 women; mean age 23.1 years; 41 with spontaneous urticaria (13 ASU and
      28 CSU), 48 with AD] and 96 healthy controls were enrolled in the study. Patients
      with ASU had the highest neopterin levels, and all three groups of patients (ASU,
      CSU and AD) had higher values than normal subjects. This preliminary study
      demonstrates that serum neopterin could be a biomarker of immune activation in
      patients with SU or AD.

PMID- 20804509
TI  - Role of Ras-related C3 botulinum toxin substrate 2 (Rac2), NADPH oxidase and
      reactive oxygen species in diallyl disulphide-induced apoptosis of human
      leukaemia HL-60 cells.
AB  - 1. Diallyl disulphide (DADS) has potential as a chemopreventive and therapeutic
      agent. Previous studies have reported that Ras-related C3 botulinum toxin
      substrate 2 (Rac2), a regulatory subunit of the NADPH oxidase complex, is
      upregulated in DADS-induced apoptosis in human leukaemia HL-60 cells. The aim of
      the present study was to investigate the role of Rac2, NADPH oxidase and reactive
      oxygen species (ROS) in DADS-induced apoptosis. 2. Expression of the Rac2 gene
      along with that of five other genes of NADPH oxidase subunits were in HL-60 cells
      measured by Sybergreen quantitative real-time polymerase chain reaction. RNA
      interference was used to test the effect of Rac2. Protein expression was
      evaluated using western blot analysis and ROS levels were measured by 2',7'
      dichlorofluorescein diacetate (DCFH-DA) fluorescence. DNA fragmentation and flow
      cytometry analysis were used to detect apoptotic cells. 3. Levels of Rac2 gene
      and protein were significantly upregulated and NADPH oxidase was activated in
      DADS-induced apoptosis. Pretreatment of HL-60 cells with small interfering (si)
      RNAs to inhibit Rac2 blocked DADS-induced apoptosis. Diallyl disulphide-induced
      intracellular ROS production was increased in phorbol myristate acetate
      stimulated cells, but decreased in Rac2 siRNA-treated cells. In Rac2 siRNA
      treated cells, activator protein-1 and caspase 3 levels decreased, c-myc protein
      levels were increased and p38 protein levels were unchanged compared with Rac2
      competent, DADS-treated cells. 4. These results demonstrate that NADPH oxidase is
      the main source of DADS-induced ROS. In addition, Rac2 selectively activates the
      c-Jun N-terminal kinase pathway, but not the p38 pathway, in DADS-induced
      apoptosis. So, Rac2, NADPH oxidase and ROS have a critical role in DADS-induced
      apoptosis in human leukaemia HL-60 cells.

PMID- 20804510
TI  - Increased Ca2+ sensitivity of myofibrillar tension in ischaemic vs dilated
      cardiomyopathy.
AB  - 1. There is evidence that different aetiologies of heart failure, especially
      ischaemic vs dilated cardiomyopathy (ICM and DCM, respectively), may influence
      the prognosis of patients with this disease. Patients with ICM have a worse
      prognosis than those with DCM; the mechanisms underlying this difference have not
      yet been clarified. The aim of the present study was to investigate whether there
      are changes in myofibrillar function depending on the aetiology of human heart
      failure. 2. Ca(2+) -dependent tension (DT) and actomyosin ATPase activity (MYO)
      in Triton X-skinned fibre preparations of the left ventricular myocardium from
      patients with heart failure due to ICM (n=5) and DCM (n=5) were measured. Tension
      dependent ATP consumption was calculated by the ratio of DT and MYO ('tension
      cost'). Non-failing myocardium (NF) from donor hearts, which could not be
      transplanted because of technical reasons, was evaluated as a control. 3.
      Although DT was reduced, the myofibrillar Ca(2+) sensitivity of DT and MYO, as
      well as tension cost, were increased in preparations from ICM and DCM myocardium
      compared with NF. The Ca(2+) sensitivity of DT and MYO was significantly
      increased in ICM compared with DCM preparations, resulting in more economic cross
      bridge cycling in ICM than in DCM. 4. In conclusion, ICM is associated with an
      increased Ca(2+) sensitivity of myofibrillar tension and ATPase activity
      accompanied by decreased tension cost compared with DCM. Thus, the worse
      prognosis associated with ICM does not seem to be due to differences in
      myofibrillar function.

PMID- 20804511
TI  - Executive function and theory of mind in school-aged children after neonatal
      corrective cardiac surgery for transposition of the great arteries.
AB  - AIM: cardiac malformations resulting in cyanosis, such as transposition of the
      great arteries (TGA), have been associated with neurodevelopmental dysfunction.
      The purpose of this study was to assess, for the first time, theory of mind
      (ToM), which is a key component of social cognition and executive functions in
      school-aged children with TGA. METHOD: twenty-one children (14 males, seven
      females; mean age 7y 4mo; SD 3mo) who underwent neonatal open-heart surgery for
      TGA using full-flow cardiopulmonary bypass were compared with 21 typically
      developing age-matched children (12 males, nine females; mean age 7y 6mo; SD
      3.8mo) using different neuropsychological measures specifically designed to
      assess executive function (cognitive and response inhibition, verbal and spatial
      working memory, and planning). They were also given two ToM tasks (first- and
      second-order false belief understanding). RESULTS: general IQ was within the
      normal range in both the TGA group and the comparison group (mean IQ 113 [SD 9.3]
      and 118 [SD 10.1] respectively), but performance on all executive functions and
      on ToM (first and second level) was significantly lower in the TGA group (p
      values of 0.02, 0.01, and 0.004 respectively). A discriminant multivariate
      analysis provided evidence for cognitive and behavioural inhibition as well as
      performance on false belief tasks as being the most important contributors to the
      differentiation between the groups (p=0.03). INTERPRETATION: children with TGA
      demonstrate great difficulties in exerting cognitive and behavioural inhibition.
      They also present specific deficits in false belief understanding, which were
      related to immature executive abilities.

PMID- 20804512
TI  - Theory of mind deficits in children with congenital heart disease.

PMID- 20804513
TI  - Outcome following decompressive craniectomy for malignant middle cerebral artery
      infarction in children.
AB  - AIM: Mortality from malignant middle cerebral artery infarction (MMCAI)
      approaches 80% in adult series. Although decompressive craniectomy decreases
      mortality and leads to an acceptable outcome in selected adult patients, there
      are few data on MMCAI in children with stroke. This study evaluated the frequency
      of MMCAI and the use of decompressive craniectomy in children. METHOD: We
      retrospectively reviewed cases of MMCAI from five pediatric tertiary care
      centers. RESULTS: Ten children (two females, eight males; median age 9y 10mo,
      range 22mo-14y) had MMCAI, with a median Glasgow Coma Scale score of 6 (range 3
      9). MMCAI represented fewer than 2% of cases of pediatric arterial ischemic
      stroke. Three patients who did not undergo decompression, all of whom had
      monitoring of intracranial pressure, developed intractable intracranial
      hypertension, and fulfilled criteria for brain death. In contrast, seven patients
      underwent decompressive craniectomy and survived, with rapid improvement in their
      level of consciousness postoperatively. All seven survivors now walk
      independently with mild to moderate residual hemiparesis and speak fluently, even
      though four had left-sided infarcts. INTERPRETATION: Decompressive craniectomy
      can lead to a moderately good outcome for children with MMCAI and should be
      considered, even with symptomatic stroke and deep coma. Monitoring of
      intracranial pressure may delay life-saving treatment.

PMID- 20804514
TI  - Motor proficiency of 6- to 9-year-old children with speech and language problems.
AB  - AIM: This study compared the gross motor skills of school-age children (mean age
      7 y 8 mo, range 6-9 y) with developmental speech and language disorders (DSLDs;
      n=105; 76 males, 29 females) and typically developing children (n=105; 76 males,
      29 females). The relationship between the performance parameters and the
      children's age was investigated as well as the role of the type of DSLD. METHOD:
      The children with DSLDs were classified by their schools' speech and language
      therapists into three subgroups: children with speech disorders (n=16), those
      with language disorders (n=41), or those with both (n=48). They were tested with
      the Test of Gross Motor Development, 2nd edition. RESULTS: Compared with their
      typically developing peers, all three DSLD subgroups scored lower on the
      locomotor (all p values<0.001) and object control sub tests (all p values<0.001).
      Significant performance differences were found between the three types of DSLD
      (all p values<0.01) where the children with language disorders only performed
      better. Older children performed better than the younger ones (plocomotor=0.029,
      pobject control<0.001), but the magnitude of differences between the children
      with DSLDs and their peers did not change with increasing age. INTERPRETATION:
      Children with DSLDs have poor gross motor skills. Although the performance of
      children with DSLDs improves with increasing age, it lags behind that of
      typically developing children. The present results emphasize the importance of
      early diagnosis and intervention for children with motor deficits.

PMID- 20804515
TI  - Undercarboxylated matrix Gla protein is associated with indices of heart failure
      and mortality in symptomatic aortic stenosis.
AB  - OBJECTIVE: Matrix Gla protein (MGP) is a calcification inhibitor and alterations
      in circulating MGP have been observed in different populations characterized by
      vascular calcification. We hypothesized that patients with calcific valvular
      aortic stenosis (AS) would have dysregulated circulating MGP levels. DESIGN AND
      SUBJECTS: We examined plasma levels of nonphosphorylated carboxylated and
      undercarboxylated MGP (dp-cMGP and dp-ucMGP, respectively) in 147 patients with
      symptomatic severe AS and in matched healthy controls. MAIN OUTCOME MEASURES: We
      further investigated the relationship between MGP levels and aortic pressure
      gradients and valve area by echocardiography and measures of heart failure.
      Finally, we assessed the prognostic value of elevated plasma dp-ucMGP level in
      relation to all-cause mortality in patients with AS. RESULTS: We found markedly
      enhanced plasma levels of dp-cMGP and in particular of dp-ucMGP in patients with
      symptomatic AS. Although only weak correlations were found with the degree of AS,
      circulating dp-ucMGP was associated with cardiac function and long-term mortality
      in multivariate analysis. CONCLUSIONS: A dysregulated MGP system may have a role
      in the development of left ventricular dysfunction in patients with symptomatic
      AS.

PMID- 20804516
TI  - Not a simple fat-soluble vitamin: Changes in serum 25-(OH)D levels are predicted
      by adiposity and adipocytokines in older adults.
AB  - OBJECTIVE: To determine the associations between body adiposity and change in
      serum 25-(OH)D levels over 2.6 years, and if these associations are mediated by
      metabolic and inflammatory factors in older adults. METHODS: This is a
      longitudinal study of 859 randomly selected subjects (mean 62 years, range 51-80,
      49% women). Serum 25-hydroxyvitamin D [25-(OH)D] was assessed by radioimmunoassay
      at baseline and 2.6 years later. Baseline serum level of leptin was assessed by
      radioimmunoassay and interleukin (IL)-6 by a chemiluminescent immunoassay in the
      first 183 subjects. RESULTS: In multivariable analyses, body mass index, trunk
      fat percentage and waist-to-hip ratio were significant predictors of increased
      incident vitamin D deficiency [a 25-(OH)D < 50 nmol L-1 at follow-up when >=50
      nmol L-1 at baseline] and decreased recovery of vitamin D deficiency [a 25-(OH)D
      >= 50 nmol L-1 at follow-up when < 50 nmol L-1 at baseline]. Change in 25-(OH)D
      levels per annum was also independently predicted by baseline leptin (beta: 
      0.09/unit, 95% CI: -0.17, -0.03), IL-6 (beta: -0.68/quartile, 95% CI: -1.35, 
      0.02) and total cholesterol/high-density lipoprotein (HDL) ratio (beta: -0.51,
      95% CI: -0.88, -0.14). The associations between body adiposity measures and
      change in 25-(OH)D completely disappeared after adjustment for leptin, diminished
      after adjustment for IL-6, but remained unchanged after adjustment for total
      cholesterol/HDL ratio. All associations were independent of season and sun
      exposure. CONCLUSIONS: Body fat is not simply a passive reservoir for 25-(OH)D.
      In addition to season and sun exposure, 25-(OH)D levels appear to be determined
      by metabolic and, to a lesser extent, inflammatory factors, and these appear to
      mediate the effects of adiposity on change in 25-(OH)D.

PMID- 20804517
TI  - New aspects of HbA1c as a risk factor for cardiovascular diseases in type 2
      diabetes: an observational study from the Swedish National Diabetes Register
      (NDR).
AB  - AIMS: To analyse the association between glycosylated haemoglobin A1c (HbA1c) and
      cardiovascular disease (CVD) in patients with type 2 diabetes in the Swedish
      National Diabetes Register (NDR). METHODS: An observational study of 18 334
      patients (age 30-79 years, previous CVD in 18%, baseline HbA1c 5.0-10.9%) who
      were followed for 6 years (mean 5.6 years) from 1997/1998 until 2003. RESULTS:
      Hazard ratios per 1% unit increase in baseline or updated mean HbA1c for
      fatal/nonfatal coronary heart disease (CHD), CVD and total mortality were 1.11
      1.13, 1.10-1.11 and 1.09-1.10, respectively (all P < 0.001), adjusted for several
      risk factors and clinical characteristics in Cox regression. Adjusted 6-year
      event rates increased with higher baseline or updated mean HbA1c with no J-shaped
      risk curves, in all patients and also when subgrouping by shorter (mean 3 years)
      or longer (mean 14 years) diabetes duration, by presence or absence of previous
      CVD, or by treatment with oral hypoglycaemic agents (OHAs) or insulin. Risk
      reductions of 20% for CHD and 16% for CVD (P < 0.001) were found in patients with
      a baseline mean HbA1c of 6.5%, compared to those with a mean level of 7.5%.
      Compared to OHA-treated patients, insulin-treated patients had an increased risk
      of total mortality, due almost exclusively to an increased risk of non-CVD
      mortality, and due less to a weakly significant increased risk of fatal CVD.
      HbA1c was not associated with non-CVD mortality. CONCLUSIONS: This observational
      study showed progressively increasing risks of CHD, CVD and total mortality with
      higher HbA1c, and no risk increase at low HbA1c levels even with longer diabetes
      duration, previous CVD or treatment with either insulin or OHAs. Patients
      achieving HbA1c <7% showed benefits for risk reduction.

PMID- 20804518
TI  - Interleukin family member ST2 and mortality in acute dyspnoea.
AB  - OBJECTIVES: The study objective was to investigate the prognostic utility and
      patient-specific characteristics of ST2 (suppression of tumorigenicity 2),
      assessed with a novel sensitive assay. BACKGROUND: Suppression of tumorigenicity
      2 signalling has been shown to be associated with death in cardiac and pulmonary
      diseases. DESIGN/SUBJECTS: In an international multicentre cohort design, we
      prospectively enrolled 1091 patients presenting with acute dyspnoea to the
      emergency department (ED). ST2 was measured in a blinded fashion using a novel
      assay and compared to B-type natriuretic peptide (BNP) and NT-proBNP. The primary
      end-point was mortality within 30 days and 1 year. The prognostic value of ST2
      was evaluated in comparison and in addition to BNP and NT-proBNP. RESULTS:
      Suppression of tumorigenicity 2 concentrations was higher amongst decedents than
      among survivors (median 85 vs. 43 U mL-1, P < 0.001) and also higher in patients
      with impaired left ventricular ejection fraction (LVEF) when compared with
      preserved LVEF (P < 0.001). In receiver operator characteristics analysis, the
      area under the curve (AUC) for ST2, BNP and NT-proBNP to predict 30-day and 1
      year mortality were 0.76, 0.63 and 0.71, and 0.72, 0.71 and 0.73, respectively.
      The combinations of ST2 with BNP or NT-proBNP improved prediction of mortality
      provided by BNP or NT-proBNP alone. After multivariable adjustment, ST2 values
      above the median (50 U mL-1) significantly predicted 1-year mortality (HR 2.3, P
      < 0.001). CONCLUSION: In patients presenting to the ED with acute dyspnoea, ST2
      is a strong and independent predictor of 30-day and 1-year mortality and might
      improve risk stratification already provided by BNP or NT-proBNP.

PMID- 20804519
TI  - Interactions of the prion peptide (PrP 106-126) with brain capillary endothelial
      cells: coordinated cell killing and remodeling of intercellular junctions.
AB  - We studied here the interactions of PrP 106-126, a peptide corresponding to the
      prion protein (PrP) amyloidogenic region, with a blood-brain barrier in vitro
      model consisting of confluent porcine brain endothelial cells (PBEC). PrP 106-126
      interacted selectively with PBEC via their luminal side, and caused cumulative
      cell death, as shown by lactate dehydrogenase release, 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide reduction, Caspase 3 induction and direct
      cell counting. In addition, PrP 106-126, but not its corresponding scrambled
      peptide, produced a 50% reduction of the trans-endothelial electrical resistance,
      while the PBEC maintained confluency. This process was accompanied by a 23%
      increase of PBEC average size and the selective disappearance from the cell
      borders of the junction proteins occludin, claudin-5 and VE-cadherin (but not ZO
      1), as evaluated by immunostaining. These results fit with a mechanism by which
      PrP 106-126 initiates a coordinated cell killing process ultimately causing the
      remaining cells to undergo a coordinated remodeling of the intercellular
      junctions and an expansion of their cell territory.

PMID- 20804521
TI  - Idiopathic intracranial hypertension in the USA: the role of obesity in
      establishing prevalence and healthcare costs.
AB  - This study documents for the first time the extraordinary costs to take care of
      patients with a chronic, non-fatal, relatively rare disorder who have been
      incorrectly thought to have an insignificant and self-limiting illness.
      Idiopathic intracranial hypertension (IIH) occurs worldwide and in all racial
      groups and is found predominantly in obese women (~ 90%) of childbearing age.
      Although the incidence of IIH is increasing as a result of the rapid increase in
      obesity, the disorder in general receives little recognition, and no recognition
      of the extensive burden of healthcare costs placed on patients, their families
      and society. We established for the first time both the prevalence of IIH in the
      USA and the direct and indirect costs of IIH using a prevalence-based model. IIH
      patients had an exceptionally high hospital admission rate of 38% (in 2007), a
      partial reflection of unsatisfactory treatment options. The total hospital costs
      per IIH admission in 2007 were four times greater than for a population-based per
      person admission. Total economic costs of IIH patients exceeded $444 million.
      Programmes designed to reduce obesity prior to and after diagnosis and better
      therapeutics will have a tremendous economic impact.

PMID- 20804520
TI  - Plasticity of vagal brainstem circuits in the control of gastric function.
AB  - BACKGROUND: Sensory information from the viscera, including the gastrointestinal
      (GI) tract, is transmitted through the afferent vagus via a glutamatergic synapse
      to neurons of the nucleus tractus solitarius (NTS), which integrate this sensory
      information to regulate autonomic functions and homeostasis. The integrated
      response is conveyed to, amongst other nuclei, the preganglionic neurons of the
      dorsal motor nucleus of the vagus (DMV) using mainly GABA, glutamate and
      catecholamines as neurotransmitters. Despite being modulated by almost all the
      neurotransmitters tested so far, the glutamatergic synapse between NTS and DMV
      does not appear to be tonically active in the control of gastric motility and
      tone. Conversely, tonic inhibitory GABAergic neurotransmission from the NTS to
      the DMV appears critical in setting gastric tone and motility, yet, under basal
      conditions, this synapse appears resistant to modulation. PURPOSE: Here, we
      review the available evidence suggesting that vagal efferent output to the GI
      tract is regulated, perhaps even controlled, in an 'on-demand' and efficient
      manner in response to ever-changing homeostatic conditions. The focus of this
      review is on the plasticity induced by variations in the levels of second
      messengers in the brainstem neurons that form vago-vagal reflex circuits.
      Emphasis is placed upon the modulation of GABAergic transmission to DMV neurons
      and the modulation of afferent input from the GI tract by
      neurohormones/neurotransmitters and macronutrients. Derangement of this 'on
      demand' organization of brainstem vagal circuits may be one of the factors
      underlying the pathophysiological changes observed in functional dyspepsia or
      hyperglycemic gastroparesis.

PMID- 20804522
TI  - Do nutrient-gut-microbiota interactions play a role in human obesity, insulin
      resistance and type 2 diabetes?
AB  - The current obesity and type 2 diabetes pandemics have causes beyond changes in
      eating and exercise habits against a susceptible genetic background. Gut bacteria
      seem to additionally contribute to the differences in body weight, fat
      distribution, insulin sensitivity and glucose- and lipid-metabolism. Data, mostly
      derived from preclinical studies, suggest that gut microbiota play an important
      role in conditions such as obesity, diabetes, metabolic syndrome and non
      alcoholic fatty liver disease. Regulation of energy uptake from the gut, by
      digesting otherwise indigestible common polysaccharides in our diet, production
      or activation of signalling molecules involved in host metabolism, modification
      of gut permeability, the release of gut hormones and inflammation, are among the
      mechanisms by which gut microbiota may influence the host cardiometabolic
      phenotype. Recent evidence suggests that quantitative and qualitative differences
      in gut microbiota exist between lean and obese, and between diabetic and non
      diabetic individuals. Modification of the gut microbiota composition and/or its
      biochemical capacity by specific dietary or pharmacological interventions may
      favourably affect host metabolism. Large-scale intervention trials, investigating
      the potential benefit of prebiotics and probiotics in improving cardiometabolic
      health in high-risk populations, are eagerly awaited.

PMID- 20804523
TI  - A review of web-based weight loss interventions in adults.
AB  - Unprecedented obesity rates are changing the burden of disease worldwide and
      obesity-related health complications are increasing healthcare costs. In
      response, researchers, clinicians and public health practitioners are seeking new
      and effective tools such as the Internet to effect weight loss. This review
      highlights peer-reviewed literature on randomized controlled trials that examine
      Internet-delivered weight loss and maintenance programmes. The scope of this
      review is broader than previous reviews, including more males and non-Caucasian
      participants. The reviewed studies show intervention results ranging from no
      weight loss to an average loss of 7.6 kg. It is difficult to draw a definitive
      conclusion on the potential impact of Internet-based weight loss as study methods
      are highly variable between papers, low adherence was recorded and not all
      studies include a control group. As the demand for low-cost, efficacious
      interventions that yield statistically significant and/or clinically relevant
      results grows, more rigorous, population-specific research is needed to determine
      if Internet-delivered interventions may slow or reverse with weight gain and
      obesity and the associated health consequences.

PMID- 20804524
TI  - Experiences and attitudes of nurse specialists in primary care regarding their
      role in care for patients with urinary incontinence.
AB  - AIM: To explore experiences and attitudes of nurse specialists in primary care
      regarding their role in care for patients with urinary incontinence (UI), thereby
      identifying facilitators and barriers for wider implementation. BACKGROUND:
      Currently, primary care for patients with UI lacks sufficient adherence to
      existing guidelines on UI and is far from optimal. Studies in various countries
      show that involving nurse specialists may offer a solution to the inadequate care
      for UI. As qualitative studies on experiences of nurses with this type of
      intervention are lacking, we performed this study with a qualitative approach and
      data collection method within the course of a randomized controlled trial (RCT).
      METHOD: A focus group study was conducted in 2007 with six nurse specialists who
      were trained in caring for patients with UI in our pragmatic RCT. The focus group
      interview was audio-taped and transcribed verbatim. The data were analysed using
      qualitative content analysis to identify themes. To understand obstacles and
      incentives for change, we relied on an existing 'implementation model'. FINDINGS:
      Nurse specialists feel competent to provide advice and information, to offer
      possible solutions and to give attention and guidance to the process of care of
      people with UI. They feel appreciated by patients and feel they offer an added
      value to the usual care of general practitioners (GPs). Nurses sometimes notice
      that GPs lack interest in UI. Personal contact with the GPs, availability of
      enough time, adequate equipment and financial resources are important
      preconditions for effective nurse specialist care. Nurse specialists value
      continuous education and feedback in daily care for patients with UI. CONCLUSION:
      Trained nurse specialists appeared to feel competent and satisfied to support GPs
      in care for patients with UI. They feel highly appreciated by both patients and
      GPs.

PMID- 20804525
TI  - Burnout as an existential deficiency--lived experiences of burnout sufferers.
AB  - Aiming at a deeper and existential understanding of burnout, by looking
      especially at the patterns of health, suffering and expressions of understanding
      of life in a longitudinal perspective, qualitative data from 18 Swedish women and
      men were analysed. Burnout as an illness has been subject to constant questioning
      during its incidence in western societies. Yet it is generally agreed that people
      afflicted by burnout experience huge problems and suffering. Data from interviews
      face to face, telephone follow-up interviewing during 1 year and e-mail interview
      dialogues were collected. With a nursing science perspective in which health and
      suffering are basic concepts, an interpretive analysis revealed signs of
      existential deficiencies in the lived experience of the people afflicted. The
      images of the patterns of lived experience elucidated reveal a discord between
      the people and their work, a blindness towards their own actions, bodily illness
      as signs of burnout, experiencing a collapse as a 'crossroad', secondary
      suffering related to the social system and a struggle towards a way out. Our
      interpretation reveals assumptions concerning three levels of life: actions,
      values and universal existence, which is somewhat different from previous
      studies. Unless a person is in contact with these three dimensions, he/she seems
      to find it difficult to maintain health in his/her encounters with life.
      Implications for health care are existential interest on the part of caregivers
      and understanding of life as signs of universal values. Patients''shut off' and
      restrained longings understood as signs of 'darkness' in their understanding of
      life may induce caring acts on the part of caregivers that offer patients an
      opening and a glimpse of what it might be like to find health in the midst of
      their suffering. The caregivers' own natural light of understanding of life can
      then work as a caring component.

PMID- 20804526
TI  - Cardiovascular and demographic characteristics in whole blood and plasma donors:
      results from the Donor InSight study.
AB  - BACKGROUND: Within blood establishments little comparative information is
      available about donors versus the general population. In this study, a
      description of the donor pool was made in terms of demographic factors and
      cardiovascular risk factors. The general Dutch population was used as a reference
      group. STUDY DESIGN AND METHODS: The Donor InSight study provided information on
      donors. Extensive information has been gathered by a self-administered
      questionnaire addressing various topics, like demographics, lifestyle, and
      health. Aggregated donor responses were compared with general population summary
      data. RESULTS: The study population consisted of 15,076 donors. The median age
      was 46.3 years and 47.3% were men. Donors were more likely to be highly educated
      (34.6%), married (71.7%), and of Dutch origin (97.4%), when compared to the
      general population. Donors were less often smokers (donors, 17.1%; general
      population, 31.8%), more often moderate drinkers (donors, 82.8%; general
      population, 74.7%), and physically more active (donors, 2.0 hr/week; general
      population, 1.0 hr/week). Male donors were more often moderately overweight
      (47.7%) than men from the general population (39.9%). In donors, 0.9% reported to
      have Type 2 diabetes versus 1.9% in the general population. In donors, 3.4%
      reported high cholesterol versus 4.6% in the general population. CONCLUSION: The
      study provided important knowledge about demographic distributions and
      cardiovascular risk factors within donors. A proper understanding of demographic
      characteristics of donors will help us to focus recruitment and retention
      strategies. The reported beneficial cardiovascular profile suggests a need for
      further research on the role of blood donation in cardiovascular risk reduction.

PMID- 20804528
TI  - Evaluation of a new cell separator for collection of peripheral blood CD34+
      progenitor cells in pediatric patients.
AB  - BACKGROUND: This study was conducted to evaluate the performance of the COM.TEC
      cell separator (Fresenius HemoCare GmbH) for collecting CD34+ cells in pediatric
      patients who were intended to have autologous peripheral blood progenitor cell
      transplantation, with respect to collection variables, prediction power of CD34+
      cell yield, and influence on donors. STUDY DESIGN AND METHODS: A total of 26
      pediatric solid tumor patients who received mobilization chemotherapy and
      granulocyte-colony-stimulating factor underwent CD34+ cell collection (n = 96)
      using the COM.TEC auto mononuclear cell (MNC) program. Patients were divided into
      a neuroblastoma (NBL) group and a brain tumor group according to the intensity of
      prior chemotherapy regimens. The collection variables, cellular variables of
      leukapheresis products, and the peripheral blood cell counts of patients were
      compared with those acquired using the COBE Spectra (GambroBCT). The CD34+ cell
      collection efficiency (CE) and the percentage ratios of actual to predicted CD34+
      cell yield indicating prediction power were analyzed. RESULTS: Using the COM.TEC
      auto MNC program, the processing rate was higher and the product volume was
      smaller (p < 0.05) than those of the COBE Spectra. Platelet (PLT) reduction in
      peripheral blood and PLT contamination of the products were significantly lower
      (p < 0.01). The median CE was less than 60% in both patient groups (50.0 and
      48.4%, respectively). The actual collected CD34+ cell yields were medians of 66.9
      and 76.1% of the predicted values in NBL group and brain tumor group,
      respectively. CONCLUSION: PBPC collections by the COM.TEC cell separator had
      advantages of high processing rate, low product volume, and low contamination by
      PLTs of product. Low PLT loss was observed in pediatric patients who need to
      collect autologous PBPCs. However, applying CD34+ cell yield prediction was not
      practical for prospective scheduling of the next collection. More specified data
      need to be accumulated for more accurate prediction of CD34+ cell yield in
      pediatric patients.

PMID- 20804527
TI  - Iron deficiency in blood donors: analysis of enrollment data from the REDS-II
      Donor Iron Status Evaluation (RISE) study.
AB  - BACKGROUND: Regular blood donors are at risk of iron deficiency, but
      characteristics that predispose to this condition are poorly defined. STUDY
      DESIGN AND METHODS: A total of 2425 red blood cell donors, either first-time (FT)
      or reactivated donors (no donations for 2 years) or frequent donors, were
      recruited for follow-up. At enrollment, ferritin, soluble transferrin receptor
      (sTfR), and hemoglobin were determined. Donor variables included demographics,
      smoking, dietary intake, use of iron supplements, and menstrual and/or pregnancy
      history. Models to predict two measures of iron deficiency were developed: Absent
      iron stores (AIS) were indicated by a ferritin level of less than 12 ng/mL and
      iron-deficient erythropoiesis (IDE) by a log(sTfR/ferritin) value of 2.07 or
      greater. RESULTS: A total of 15.0% of donors had AIS and 41.7% IDE. In frequent
      donors, 16.4 and 48.7% of males had AIS and IDE, respectively, with corresponding
      proportions of 27.1 and 66.1% for females. Donation intensity was most closely
      associated with AIS and/or IDE (odds ratios from 5.3 to 52.2 for different
      donation intensity compared to FT donors). Being female, younger, and/or
      menstruating also increased the likelihood of having AIS and/or IDE, as did
      having a lower weight. Marginally significant variables for AIS and/or IDE were
      being a nonsmoker, previous pregnancy, and not taking iron supplements. Dietary
      variables were in general unrelated to AIS and/or IDE, as was race and/or
      ethnicity. CONCLUSION: A large proportion of both female and male frequent blood
      donors have iron depletion. Donation intensity, sex and/or menstrual status,
      weight, and age are important independent predictors of AIS and/or IDE. Reducing
      the frequency of blood donation is likely to reduce the prevalence of iron
      deficiency among blood donors, as might implementing routine iron
      supplementation.

PMID- 20804529
TI  - Changes of cytokine levels during granulocyte-colony-stimulating factor stem cell
      mobilization in healthy donors: association with mobilization efficiency and
      potential predictive significance.
AB  - BACKGROUND: Peripheral blood stem cells are an important source of hematopoietic
      stem cells (HSCs) for allogeneic transplantations. Some allogeneic donors
      mobilize HSCs poorly in response to the granulocyte--colony-stimulating factor (G
      CSF). The estimation of the mobilization result in an individual donor is
      difficult due to the absence of suitable predictive factors. STUDY DESIGN AND
      METHODS: We analyzed the concentrations and kinetics of certain cytokines induced
      by G-CSF in 76 healthy donors and compared them with the mobilization efficiency.
      RESULTS: The levels of the most cytokines increased after the G-CSF application:
      sICAM, sVCAM, MMP-9, interleukin (IL)-6, TNF-alpha, sE-selectin, and fibronectin.
      The concentrations of SDF-1alpha and IL-8 decreased and VEGF and fractalkine
      remained unchanged. The premobilization concentrations of IL-6 (p = 0.0093) and
      TNF-a (p = 0.0006) correlated with preapheresis CD34+ cell count. The comparison
      of premobilization cytokine levels between better and worse mobilizers showed a
      difference for TNF-alpha (p = 0.0006) and IL-6 (p = 0.0682). The TNF-alpha level
      below cutoff of 3.6 pg/mL implied approximately 20 times higher risk of poor
      mobilization (odds ratio, 19.9; p = 0.0002). The immunophenotyping of CD34+ cells
      suggested a negative correlation between Day +5 CD34+ count and expression of
      CD11a (p = 0.0319) and a positive correlation with CD44 antigen expression (p =
      0.0096). CONCLUSION: The concentrations of certain cytokines corresponded to the
      quality of HSC mobilization in healthy donors. Their levels measured before
      mobilization could probably serve as predictive factors for mobilization efficacy
      and prospectively detect donors who might profit from new mobilization molecules.

PMID- 20804531
TI  - Cause-specific mortality associated with leukoreduced, buffy coat-depleted, or no
      blood transfusion after elective surgery for colorectal cancer: a posttrial 15
      year follow-up study.
AB  - BACKGROUND: We previously reported that both leukoreduced (LR) and buffy coat
      depleted (BCD) blood transfusions had a detrimental effect on long-term overall
      survival in patients who underwent elective surgery for colorectal disease. This
      analysis investigates long-term cause-specific mortality in trial participants
      diagnosed with colorectal cancer (CRC). STUDY DESIGN AND METHODS: We used the
      Danish Civil Registration System to follow 448 trial participants with CRC, from
      their enrollment in 1992 to 1995 until January 2007. A total of 108 patients were
      transfused with BCD blood, 94 with LR blood, and 246 did not receive a
      transfusion (NT). We reviewed death certificates for study patients who died
      during follow-up. Cause-of-death data were coded according to the International
      Classification of Diseases (ICD-8 and -10). The Charlson Comorbidity Index was
      used for risk adjustment. RESULTS: A total of 43% of NT, 28% of BCD, and 27% of
      LR transfused patients were alive after 15 years of follow-up (p = 0.001 for
      transfused vs. NT patients). For LR-transfused versus NT patients the adjusted
      mortality ratio for death from rectal cancer was 1.81 (95% confidence interval
      [CI], 0.97-3.38), and for death from cardiovascular disease 2.12 (95% CI, 1.23
      3.62). For BCD versus NT patients the adjusted mortality ratio for death from
      rectal cancer was 1.19 (95% CI, 0.61-2.33) and for cardiovascular disease it was
      1.68 (95% CI, 0.97-2.91). CONCLUSION: LR transfusion is associated with decreased
      long-term survival due to death from cardiovascular disease. A similar but weaker
      tendency was observed for BCD transfusion.

PMID- 20804532
TI  - The use of fresh-frozen plasma in England: high levels of inappropriate use in
      adults and children.
AB  - BACKGROUND: Fresh-frozen plasma (FFP) is given to patients across a range of
      clinical settings, frequently in association with abnormalities of standard
      coagulation tests. STUDY DESIGN AND METHODS: A UK-wide study of FFP transfusion
      practice was undertaken to characterize the current patterns of administration
      and to evaluate the contribution of pretransfusion coagulation tests. RESULTS: A
      total of 4969 FFP transfusions given to patients in 190 hospitals were analyzed,
      of which 93.3% were in adults and 6.7% in children or infants. FFP transfusions
      to adults were given most frequently in intensive-treatment or high-dependency
      units (32%), in operating rooms or recovery (23%), or on medical wards (22%). In
      adult patients 43% of all FFP transfusions were given in the absence of
      documented bleeding, as prophylaxis for abnormal coagulation tests or before
      procedures or surgery. There was wide variation in international normalized ratio
      (INR) or prothrombin times before FFP administration; in 30.9% of patients where
      the main reason for transfusion was prophylactic in the absence of bleeding the
      INR was 1.5 or less. Changes in standard coagulation results after FFP
      administration were generally very small for adults and children. CONCLUSIONS:
      This study raises important questions about the clinical benefit of much of
      current FFP usage. It highlights the pressing need for better studies to inform
      and evaluate quantitative data for the effect of plasma on standard coagulation
      tests.

PMID- 20804530
TI  - Molecular insight into human platelet antigens: structural and evolutionary
      conservation analyses offer new perspective to immunogenic disorders.
AB  - BACKGROUND: Human platelet antigens (HPAs) are polymorphisms in platelet membrane
      glycoproteins (GPs) that can stimulate production of alloantibodies once exposed
      to foreign platelets (PLTs) with different HPAs. These antibodies can cause
      neonatal alloimmune thrombocytopenia, posttransfusion purpura, and PLT
      transfusion refractoriness. Most HPAs are localized on the main PLT receptors: 1)
      integrin alphaIIbbeta3, known as the fibrinogen receptor; 2) the GPIb-IX-V
      complex that functions as the receptor for von Willebrand factor; and 3) integrin
      alpha2beta1, which functions as the collagen receptor. STUDY DESIGN AND METHODS:
      We analyzed the structural location and the evolutionary conservation of the
      residues associated with the HPAs to characterize the features that induce
      immunologic responses but do not cause inherited diseases. RESULTS: We found that
      all HPAs reside in positions located on the protein surface, apart from the
      ligand-binding site, and are evolutionary variable. CONCLUSION: Disease-causing
      mutations often reside in highly conserved and buried positions. In contrast, the
      HPAs affect residues on the protein surface that were not conserved throughout
      evolution; this explains their naive effect on the protein function. Nonetheless,
      the HPAs involve substitutions of solvent-exposed positions that lead to altered
      interfaces on the surface of the protein and might present epitopes foreign to
      the immune system.

PMID- 20804533
TI  - Splenic autotransplantation reverses interferon-gamma and nitric oxide production
      and resistance to Listeria monocytogenes in splenectomized mice.
AB  - Splenectomized mice control Listeria monocytogenes infection better than non
      splenectomized mice. Here, BALB/c mice subjected to splenectomy and autogenous
      grafting of spleen were evaluated after 3 and 7 days of intravenous L.
      monocytogenes infection. The group of splenectomized animals (SP) presented a
      lower number of bacteria in the liver in comparison with both the sham-operated
      control group (CT) and the group that received splenic autotransplantation (AT)
      in the retroperitoneal site. The AT group presented bacterial counts in the liver
      similar to the CT group. SP animals showed larger production of interferon-gamma
      (IFN-gamma) and nitric oxide (NO) in the liver in comparison with CT and AT, this
      being associated with greater accumulation of mononuclear cells. IFN-gamma
      production by spleen cells after stimulation with heat-killed Listeria was
      similar between the AT and CT groups, suggesting that the implanted fragments
      behaved like the original organ. The autogenous grafting of spleen fragments
      reverses the resistance to L. monocytogenes infection found in splenectomized
      mice, associated with a reduced IFN-gamma and NO production in the liver. The
      present study shows that splenic autotransplantation restores the function of the
      spleen in splenectomized mice, even though in this case it does favor the
      susceptibility to L. monocytogenes infection.

PMID- 20804534
TI  - Treatment of respiratory syncytial virus infection in adult patients with
      hematologic malignancies based on an institution-specific guideline.
AB  - A total of 26 adults with hematologic malignancies and/or hematopoietic stem cell
      transplant were treated for respiratory syncytial virus (RSV) infection based on
      an institutional guideline. Thirteen patients received aerosolized ribavirin, and
      13 received aerosolized ribavirin and intravenous palivizumab. Two deaths, not
      attributed to RSV infection, occurred within 90 days of diagnosis.

PMID- 20804535
TI  - Chronic norovirus gastroenteritis in a double hematopoietic stem cell and lung
      transplant recipient.

PMID- 20804536
TI  - Lack of antibodies against the antigen domain 2 epitope of cytomegalovirus (CMV)
      glycoprotein B is associated with CMV disease after renal transplantation in
      recipients having the same glycoprotein H serotypes as their donors.
AB  - Cytomegalovirus (CMV) reinfection of seropositive individuals has been associated
      with adverse outcomes in organ transplantation and is a frequent cause of
      congenital infection. Previously we demonstrated that mismatching of CMV
      glycoprotein H (gH) serotypes was associated with CMV disease after renal
      transplantation. Because the antigen domain 2 (AD2) epitope of glycoprotein B
      (gB) is conserved among CMV isolates and is one of the known targets of
      neutralizing antibodies, in this study we investigated whether antibodies against
      the epitope contribute to protection from CMV reinfection in renal
      transplantation, irrespective of gH serological matching. For this purpose, the
      gB and gH serology and clinical outcomes were analyzed retrospectively for 77
      transplant recipients in the donor positive/recipient positive setting, who were
      managed by preemptive strategy. We found that there was a good negative
      correlation between the numbers of antigenemia-positive cells and the levels of
      antibodies against gB AD2 in the CMV-gH antibody matched group, but not in the
      CMV-gH antibody mismatched group. None of the recipients with antibodies against
      both gB AD2 and strain-specific epitopes of gH have experienced CMV disease
      during 6 month after transplantation, while 28% of those who lacked either/both
      antibody response needed preemptive therapy. Because the outcome was
      statistically significant, antibodies against gB AD2 can be a useful indicator to
      predict emergence of CMV disease for preemptive therapy, in addition to
      antibodies against the mismatched gH types.

PMID- 20804537
TI  - alphaB-crystallin (HspB5) in familial amyloidotic polyneuropathy.
AB  - The small heat shock protein alphaB-crystallin (HspB5) is known to be
      overexpressed in several neurodegenerative disorders. In familial amyloidotic
      polyneuropathy (FAP), a neurodegenerative disorder characterized by extracellular
      deposition of mutated transthyretin (TTR), activation of heat shock factor 1 
      HSF1- by extracellular TTR deposition has been shown as well as induction of the
      expression of heat shock proteins, HSP27 and HSP70. Here we investigate the
      expression of alphaB-crystallin in FAP. We first detected alphaB-crystallin in
      aggregates extracted from tissues of both FAP patients and transgenic mice for
      the human V30M mutant TTR; however, subsequent studies by confocal fluorescence
      microscopy did not confirm the association of alphaB-crystallin with TTR
      aggregates; thus the presence of alphaB-crystallin in aggregate extracts might
      derive from the extraction procedure. Increased levels of alphaB-crystallin were
      observed by immunohistochemistry in human FAP skin, as compared to normal skin.
      Furthermore, skin, stomach and dorsal root ganglia from V30M transgenic mice
      showed increased expression of alphaB-crystallin as compared to controls without
      deposition. A human neuroblastoma cell line incubated with TTR aggregates
      displayed increased expression of alphaB-crystallin. Overall, these results show
      that extracellular TTR deposits induce an intracellular response of alphaB
      crystallin. This small heat shock protein (HSP), which is important for anti
      apoptotic and chaperone properties, may have a protective role in FAP.

PMID- 20804538
TI  - STAT3 modulates the DNA damage response pathway.
AB  - The STAT3 transcription factor is well known to function as an anti-apoptotic
      factor, especially in numerous malignancies. Recently we showed that STAT3 is
      cytoprotective and that cells lacking STAT3 are more sensitive to oxidative
      stress. A key feature of oxidative stress involves activation of the DNA damage
      pathway. However, a role for STAT3 or its contribution in response to DNA damage
      has not been described. In the present study we show that cells lacking STAT3 are
      less efficient in repairing damaged DNA. Moreover, STAT3 deficient cells show
      reduced activity of the ATM-Chk2 and ATR-Chk1 pathways, both important pathways
      in sensing DNA damage. Finally we show that MDC1, a regulator of the ATM-Chk2
      pathway and facilitator of the DNA damage response, is modulated by STAT3 at the
      transcriptional level. These findings demonstrate that STAT3 is necessary for
      efficient repair of damaged DNA, partly by modulating the ATM-Chk2 and ATR-Chk1
      pathways.

PMID- 20804539
TI  - Genetic regulation of pristane-induced oil granuloma responses.
AB  - Oil granuloma (OG) induced by intraperitoneal injection of pristane represents a
      non-infectious granuloma. Oil granuloma has been characterized, but the
      regulation of its formation still remains unknown. To address this, we injected
      pristane into various mice deficient for genes including, linker for activation
      of T cells (LAT), MUMT, LTalpha, TNFalpha, IL-6. T cell deficient mice (LAT(-/-)
      ) responded to pristane by developing serosal granuloma and mesenteric granuloma
      (MG) as in wild type mice. The absence of B cells blocked serosal granuloma (SG)
      formation and diminished MG development in response to pristane. However, even
      when a comparable number of B cells were present in the mesentery, the absence of
      TNFalpha resulted in similar defects in OG formation after pristane treatment,
      demonstrating that both B cells and TNFalpha are very crucial for pristane
      induced OG formation. Interestingly, IL-6(-/-) mice had intact MG formation;
      however, SG organization was impaired. These studies provide insight into
      granulomateous pathology induced by non-infectious substances for example,
      biomedical sutures.

PMID- 20804540
TI  - Erythropoietin is involved in angiogenesis in human primary melanoma.
AB  - In this study, the extent of angiogenesis, evaluated as microvascular volume
      density, immunoreactivity of tumour cells to erythropoietin (Epo) and of
      endothelial cells to Epo receptor (EpoR) have been correlated in human primary
      melanoma specimens. Results showed that Epo/EpoR expression correlate with
      angiogenesis and tumour thickness. These findings suggest that Epo is secreted by
      tumour cells and it affects vascular endothelial cells via its receptor and
      promotes angiogenesis in a paracrine manner, playing an important role in
      melanoma angiogenesis.

PMID- 20804542
TI  - Microcalcifications in atherosclerotic lesion of apolipoprotein E-deficient
      mouse.
AB  - Evidence is accumulating that calcium-rich microdeposits in the vascular wall
      might play a crucial role in the onset and progression of atherosclerosis. Here
      we investigated an atherosclerotic lesion of the carotid artery in an established
      murine model, i.e. the apolipoprotein E-deficient (APOE(-/-) ) mouse to identify
      (i) the presence of microcalcifications, if any, (ii) the elemental composition
      of microcalcifications with special reference to calcium/phosphorus mass ratio
      and (iii) co-localization of increased concentrations of iron and zinc with
      microcalcifications. Atherosclerosis was induced by a flow-divider placed around
      the carotid artery resulting in low and high shear-stress regions. Element
      composition was assessed with a proton microprobe. Microcalcifications,
      predominantly present in the thickened intima of the low shear-stress region,
      were surrounded by areas with normal calcium levels, indicating that calcium
      precipitation is a local event. The diameter of intimal microcalcifications
      varied from 6 to 70 MUm. Calcium/phosphorus ratios of microcalcifications varied
      from 0.3 to 4.8, mainly corresponding to the ratio of amorphous calcium
      phosphate. Increased iron and zinc concentrations commonly co-localized with
      microcalcifications. Our findings indicate that the atherosclerotic process in
      the murine carotid artery is associated with locally accumulated calcium, iron
      and zinc. The calcium-rich deposits resemble amorphous calcium phosphate rather
      than pure hydroxyapatite. We propose that the APOE(-/-) mouse, in which
      atherosclerosis was evoked by a flow-divider, offers a useful model to
      investigate the pathophysiological significance of accumulation of elements such
      as calcium, iron and zinc.

PMID- 20804541
TI  - Oxidative stress in obstructive nephropathy.
AB  - Unilateral ureteric obstruction (UUO) is one of the most commonly applied rodent
      models to study the pathophysiology of renal fibrosis. This model reflects
      important aspects of inflammation and fibrosis that are prominent in human kidney
      diseases. In this review, we present an overview of the factors contributing to
      the pathophysiology of UUO, highlighting the role of oxidative stress.

PMID- 20804544
TI  - Inflammatory fibroid polyp of the ileum presenting with small bowel obstruction
      in an adult patient: a case report.
AB  - INTRODUCTION: Inflammatory fibroid polyps are rare benign tumors of the
      gastrointestinal tract with the gastric antrum being the most common site,
      followed by the ileum. Histogenesis is still unknown and controversial.
      Inflammatory fibroid polyps are one of the rare benign conditions leading to
      intestinal obstruction in adults. CASE PRESENTATION: A 54-year-old Caucasian man
      presented with acute abdomen pain and a two month history of intermittent
      cramping and lower abdominal pain. Computed tomography imaging demonstrated a
      partial intestinal obstruction in the location of the terminal ileum. An ileo
      ileal intussusception due to a mass lesion 15 cm proximal to the caecum was found
      on exploratory laparotomy. Intussusception was spontaneously reduced during
      exploration and a wedge resection was performed to the affected bowel segment.
      Histopathologic examination showed the mass to be an inflammatory fibroid polyp.
      CONCLUSION: Although inflammatory fibroid polyps are rare and benign, in the case
      of intestinal obstruction the only solution is a surgical approach.

PMID- 20804543
TI  - Characteristic pattern of skeletal muscle remodelling in different mouse strains.
AB  - Muscular injury associated with local inflammatory reaction frequently occurs in
      sports medicine, but the individual response and capacity of regeneration vary
      among subjects. Inflammatory cytokines are probably implicated in activation of
      repair mechanisms by specifically influencing tissue microenvironment. This work
      aimed to compare muscle tissue repair in different mouse lineages. We used
      C57BL/6 and BALB/c mice genetically predisposed to either Type1 or Type2 cytokine
      production. The role of Type1 cytokines was also investigated in C57IFN-gamma
      (IFNgamma-KO) and C57IL-12 (IL12-KO) knockout mice. Participation of T
      lymphocytes was assessed in athymic BALB/c nude (nu/nu) mice. Muscular lesion was
      induced with bupivacaine injection in the Triceps brachii muscle. BALB/c mice
      showed marked collagen deposition and increased TGF-beta mRNA content,
      contrasting with mild fibrosis observed in C57BL/6 mice. C57-IFNgamma-KO mice,
      exhibited pronounced fibrosis, but IL12-KO collagen deposition was similar to
      that of C57. Twenty-four hours after lesion, C57BL/6 and BALB/c(nu/nu) presented
      numerous regenerating myofibres and marked increase of metalloprotease-9 activity
      compared with BALB/c. These data support that skeletal muscle remodelling is
      greatly influenced by the genetic backgrounds, shedding light on the molecular
      mechanisms influencing differential muscular remodelling and tissue regeneration
      among individuals.

PMID- 20804545
TI  - Metabolic syndrome predicts vascular changes in whole body magnetic resonance
      imaging in patients with long standing diabetes mellitus.
AB  - BACKGROUND: Although diabetic patients have an increased rate of cardio-vascular
      events, there is considerable heterogeneity with respect to cardiovascular risk,
      requiring new approaches to individual cardiovascular risk factor assessment. In
      this study we used whole body-MR-angiography (WB-MRA) to assess the degree of
      atherosclerosis in patients with long-standing diabetes and to determine the
      association between metabolic syndrome (MetS) and atherosclerotic burden.
      METHODS: Long standing (> or = 10 years) type 1 and type 2 diabetic patients (n =
      59; 31 males; 63.3 +/- 1.7 years) were examined by WB-MRA. Based on the findings
      in each vessel, we developed an overall score representing the patient's vascular
      atherosclerotic burden (MRI-score). The score's association with components of
      the MetS was assessed. RESULTS: The median MRI-score was 1.18 [range: 1.00-2.41]
      and MetS was present in 58% of the cohort (type 2 diabetics: 73%; type 1
      diabetics: 26%). Age (p = 0.0002), HDL-cholesterol (p = 0.016), hypertension (p =
      0.0008), nephropathy (p = 0.0093), CHD (p = 0.001) and MetS (p = 0.0011) were
      significantly associated with the score. Adjusted for age and sex, the score was
      significantly (p = 0.02) higher in diabetics with MetS (1.450 [1.328-1.572])
      compared to those without MetS (1.108 [0.966-1.50]). The number of MetS
      components was associated with a linear increase in the MRI-score (increase in
      score: 0.09/MetS component; r2 = 0.24, p = 0.038). Finally, using an established
      risk algorithm, we found a significant association between MRI-score and 10-year
      risk for CHD, fatal CHD and stroke. CONCLUSION: In this high-risk diabetic
      population, WB-MRA revealed large heterogeneity in the degree of systemic
      atherosclerosis. Presence and number of traits of the MetS are associated with
      the extent of atherosclerotic burden. These results support the perspective that
      diabetic patients are a heterogeneous population with increased but varying
      prevalence of atherosclerosis and risk.

PMID- 20804546
TI  - The assessment of carotid intima media thickness and serum paraoxonase-1 activity
      in Helicobacter pylori positive subjects.
AB  - BACKGROUND: The role of inflammation in the pathogenesis and progression of
      atherosclerosis has been increasingly discussed. Although the seroepidemiological
      studies have suggested a relationship between Helicobacter pylori (H. pylori)
      infection and atherosclerosis; the issue is still controversial. It is well known
      that abnormal lipid profil is related to atherosclerosis and the measurement of
      carotid-intima media thickness (CIMT) is one of the surrogate marker of
      atherosclerosis. The serum concentration of high-density lipoprotein (HDL-C) has
      been known to have an inverse correlation with the development of
      atherosclerosis. Paraoxonase-1 (PON1) is a major anti-atherosclerotic component
      of HDL-C. PON1 activity is related to lipid peroxidation and prospective
      cardiovascular risk. The aim of this study was to investigate CIMT and serum PON1
      activities along with lipid parameters in H. pylori positive and negative
      subjects. METHODS: Thirty H. pylori positive subjects and thirty-one negative
      subjects were enrolled. H. pylori infection was diagnosed by the presence of
      positivity of stool H. pylori antigen test or Carbon 14 labeled urea breath test.
      Serum PON1 activity was measured spectrophotometrically. Traditional
      cardiovascular risk factors were investigated and laboratory analysis included
      measurement of serum triglycerides (TG), total cholesterol (TC), high-density
      lipoprotein (HDL-C) and low-density lipoprotein cholesterol (LDL-C). We assessed
      CIMT by high-resolution ultrasound of both common carotid arteries. RESULTS: We
      found that the mean and maximum values of right and overall CIMT in H. pylori
      positive subjects were significantly thicker than those of H. pylori negative
      subjects. There was no significant differences in serum HDL-C, LDL-C, TC levels
      and TC/HDL-C ratios between two groups. Serum TG levels of H. pylori positive
      subjects were significantly higher than those of H. pylori negative subjects (p =
      0.014). We found that PON1 activities were significantly lower in H. pylori
      positive subjects compared with negative subjects. No significantly correlation
      was observed between PON1 and CIMT values. CONCLUSIONS: There is an increase in
      CIMT values in patients with H. pylori positive compared to H. pylori negative
      subjects. PON1 activity decrease significantly in H. pylori positive subjects.
      However, an association between PON1 and CIMT was not found. These data indicated
      that H. pylori may have a role in atherosclerotic processes, however, further
      studies are needed to evaluate the exact mechanisms.

PMID- 20804548
TI  - Relative quantification of PIK3CA gene expression level in fine-needle aspiration
      biopsy thyroid specimens collected from patients with papillary thyroid carcinoma
      and non-toxic goitre by real-time RT-PCR.
AB  - BACKGROUND: Recent studies have shown that the phosphatidylinositol 3-kinase
      (PI3K) signaling pathway is important regulator of many cellular events,
      including apoptosis, proliferation and motility. PI3K pathway alterations (PIK3CA
      gene mutations and/or amplification) have been observed in various human tumours.
      In the majority of diagnosed cases, mutations are localized in one of the three
      "hot spots" in the gene, responsible for coding catalytic subunit alpha of class
      I PI3K (PIK3CA). Mutations and amplification of PIK3CA gene are characteristic
      for thyroid cancer, as well. METHODS: The aim of our study was to examine a gene
      expression level of PIK3CA in fine-needle aspiration biopsy (FNAB) thyroid
      specimens in two types of thyroid lesions, papillary thyroid carcinoma (PTC) and
      non-toxic goitre (NTG). Following conventional cytological examination, 42
      thyroid FNAB specimens, received from patients with PTC (n = 20) and NTG (n =
      22), were quantitatively evaluated regarding PIK3CA expression level by real-time
      PCR in the ABI PRISM(r) 7500 Sequence Detection System. RESULTS: Significantly
      higher expression level (RQ) of PIK3CA in PTC group has been noted in comparison
      with NTG group (p < 0.05). CONCLUSION: These observations may suggest role of
      PIK3CA alterations in PTC carcinogenesis.

PMID- 20804547
TI  - CYP1A1 gene polymorphisms increase lung cancer risk in a high-incidence region of
      Spain: a case control study.
AB  - BACKGROUND: A rural region in south-west Spain has one of the highest lung cancer
      incidence rates of the country, as revealed by a previous epidemiological 10-year
      follow-up study. The present work was undertaken to ascertain the role of CYP1A1
      gene polymorphisms and their interaction with tobacco smoking in the development
      of the disease in this location. METHODS: One-hundred-and-three cases of lung
      cancer and 265 controls participated in the study. The participants were screened
      for the presence of four CYP1A1 polymorphisms, namely MspI, Ile462Val, T3205C,
      and Thr461Asn. Lung cancer risk was estimated as odds ratios (OR) and 95%
      confidence intervals (CI) using unconditional logistic regression models
      adjusting for age, sex, and smoking. RESULTS: The distribution of the variant
      CYP1A1 alleles was different from that described for other Caucasian populations,
      with CYP1A1*2A showing an uncommonly high frequency (p < 0.01). The CYP1A1*2B
      allele (carrying MspI and Ile462Val mutations) was strongly associated with high
      lung cancer risk (OR = 4.59, CI:1.4-12.6, p <0.01). The Ile462Val polymorphism
      was also shown to increase the risk for the disease (OR = 4.51, CI:1.8-11.9; p
      <0.01) and particularly for squamous-cell (OR = 5.01; CI: 1.6-14.3, p < 0.01) and
      small-cell lung carcinoma (SCLC) (OR = 6.97, CI: 1.2-81.3; p = 0.04). Moreover,
      the Thr461Asn polymorphism was found to be associated with SCLC in a Caucasian
      population for the first time to our knowledge (OR = 8.33, CI: 1.3-15.2, p =
      0.04). CONCLUSION: The results suggest that CYP1A1 polymorphisms contribute to
      increase lung cancer susceptibility in an area with an uncommon high incidence
      rate.

PMID- 20804549
TI  - Evaluation of NDRG2 gene expression in primary papillary thyroid carcinoma and in
      metastases of this neoplasm to regional lymph nodes.
AB  - BACKGROUND: At present, researchers' attention has been concentrating on NDRG2 (N
      Myc downstream-regulated gene 2) as a new gene candidate in the development and
      progression of papillary thyroid carcinoma (PTC). NDRG2, together with NDRG1,
      NDRG3 and NDRG4 are members of the NDRG family, a new class of genes, inhibited
      by N-Myc oncogene. AIM: The aim of our study was to evaluate NDRG2 mRNA
      expression in the primary PTC and its metastases to regional lymph nodes.
      MATERIALS AND METHODS: Postoperative tissue and macroscopically changed lymph
      nodes of sixteen (16) patients with PTC constituted the studied material. In this
      group, metastases of the cancer to regional lymph nodes were confirmed
      histopathologically in 8 cases. Quantitative evaluation of NDRG2 mRNA expression
      was performed by the real-time polymerase chain reaction (real-time PCR) method.
      RESULTS: The mean values of NDRG2 mRNA expression in the primary tumour tissues
      were statistically significantly lower vs. the levels of NDRG2 mRNA expression in
      macroscopically unchanged thyroid tissue (p < 0.0001). A comparison of the mean
      NDRG2 mRNA expression of primary tumours and that of their metastases to regional
      lymph nodes did not demonstrate any statistical differences (p > 0.05). A
      positive correlation was observed between NDRG2 mRNA expression in primary tumour
      cells and in the cancer metastases to lymph nodes (Rs = 0.7857; p < 0.05).
      Factors, such as age, sex, tumour stage in TNM system, were of no significance
      for NDRG2 mRNA expression level (p > 0.1). CONCLUSION: The results of our study
      demonstrated decreased NDRG2 mRNA expression levels in PTC, when compared to
      macroscopically unchanged thyroid tissue, which may point to the potential role
      of NDRG2 in the development and progression of cancer in question.

PMID- 20804550
TI  - COX-2 inhibition improves immunotherapy and is associated with decreased numbers
      of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC
      function.
AB  - BACKGROUND: Myeloid-derived suppressor cells (MDSC) are a heterogeneous
      population of immature cells that accumulates in tumour-bearing hosts. These
      cells are induced by tumour-derived factors (e.g. prostaglandins) and have a
      critical role in immune suppression. MDSC suppress T and NK cell function via
      increased expression of arginase I and production of reactive oxygen species
      (ROS) and nitric oxide (NO). Immune suppression by MDSC was found to be one of
      the main factors for immunotherapy insufficiency. Here we investigate if the in
      vivo immunoregulatory function of MDSC can be reversed by inhibiting
      prostaglandin synthesis by specific COX-2 inhibition focussing on ROS production
      by MDSC subtypes. In addition, we determined if dietary celecoxib treatment leads
      to refinement of immunotherapeutic strategies. METHODS: MDSC numbers and function
      were analysed during tumour progression in a murine model for mesothelioma. Mice
      were inoculated with mesothelioma tumour cells and treated with cyclooxygenase-2
      (COX-2) inhibitor celecoxib, either as single agent or in combination with
      dendritic cell-based immunotherapy. RESULTS: We found that large numbers of
      infiltrating MDSC co-localise with COX-2 expression in those areas where tumour
      growth takes place. Celecoxib reduced prostaglandin E2 levels in vitro and in
      vivo. Treatment of tumour-bearing mice with dietary celecoxib prevented the local
      and systemic expansion of all MDSC subtypes. The function of MDSC was impaired as
      was noticed by reduced levels of ROS and NO and reversal of T cell tolerance;
      resulting in refinement of immunotherapy. CONCLUSIONS: We conclude that celecoxib
      is a powerful tool to improve dendritic cell-based immunotherapy and is
      associated with a reduction in the numbers and suppressive function of MDSC.
      These data suggest that immunotherapy approaches benefit from simultaneously
      blocking cyclooxygenase-2 activity.

PMID- 20804551
TI  - Tumor growth and angiogenesis is impaired in CIB1 knockout mice.
AB  - BACKGROUND: Pathological angiogenesis contributes to various ocular, malignant,
      and inflammatory disorders, emphasizing the need to understand this process more
      precisely on a molecular level. Previously we found that CIB1, a 22 kDa
      regulatory protein, plays a critical role in endothelial cell function,
      angiogenic growth factor-mediated cellular functions, PAK1 activation, MMP-2
      expression, and in vivo ischemia-induced angiogenesis. Since pathological
      angiogenesis is highly dependent on many of these same processes, we hypothesized
      that CIB1 may also regulate tumor-induced angiogenesis. METHODS: To test this
      hypothesis, we allografted either murine B16 melanoma or Lewis lung carcinoma
      cells into WT and CIB1-KO mice, and monitored tumor growth, morphology,
      histology, and intra-tumoral microvessel density. RESULTS: Allografted melanoma
      tumors that developed in CIB1-KO mice were smaller in volume, had a distinct
      necrotic appearance, and had significantly less intra-tumoral microvessel
      density. Similarly, allografted Lewis lung carcinoma tumors in CIB1-KO mice were
      smaller in volume and mass, and appeared to have decreased perfusion. Intra
      tumoral hemorrhage, necrosis, and perivascular fibrosis were also increased in
      tumors that developed in CIB1-KO mice. CONCLUSIONS: These findings suggest that,
      in addition to its other functions, CIB1 plays a critical role in facilitating
      tumor growth and tumor-induced angiogenesis.

PMID- 20804553
TI  - Does the use of the 2009 FIGO classification of endometrial cancer impact on
      indications of the sentinel node biopsy?
AB  - BACKGROUND: Lymphadenectomy is debated in early stages endometrial cancer.
      Moreover, a new FIGO classification of endometrial cancer, merging stages IA and
      IB has been recently published. Therefore, the aims of the present study was to
      evaluate the relevance of the sentinel node (SN) procedure in women with
      endometrial cancer and to discuss whether the use of the 2009 FIGO classification
      could modify the indications for SN procedure. METHODS: Eighty-five patients with
      endometrial cancer underwent the SN procedure followed by pelvic lymphadenectomy.
      SNs were detected with a dual or single labelling method in 74 and 11 cases,
      respectively. All SNs were analysed by both H&E staining and
      immunohistochemistry. Presumed stage before surgery was assessed for all patients
      based on MR imaging features using the 1988 FIGO classification and the 2009 FIGO
      classification. RESULTS: An SN was detected in 88.2% of cases (75/85 women).
      Among the fourteen patients with lymph node metastases one-half were detected by
      serial sectioning and immunohistochemical analysis. There were no false negative
      case. Using the 1988 FIGO classification and the 2009 FIGO classification, the
      correlation between preoperative MRI staging and final histology was moderate
      with Kappa = 0.24 and Kappa = 0.45, respectively. None of the patients with grade
      1 endometrioid carcinoma on biopsy and IA 2009 FIGO stage on MR imaging exhibited
      positive SN. In patients with grade 2-3 endometrioid carcinoma and stage IA on MR
      imaging, the rate of positive SN reached 16.6% with an incidence of
      micrometastases of 50%. CONCLUSIONS: The present study suggests that sentinel
      node biopsy is an adequate technique to evaluate lymph node status. The use of
      the 2009 FIGO classification increases the accuracy of MR imaging to stage
      patients with early stages of endometrial cancer and contributes to clarify the
      indication of SN biopsy according to tumour grade and histological type.

PMID- 20804554
TI  - Phosphorylation regulates proteasomal-mediated degradation and solubility of TAR
      DNA binding protein-43 C-terminal fragments.
AB  - BACKGROUND: Inclusions of TAR DNA binding protein-43 (TDP-43) are the defining
      histopathological feature of several neurodegenerative diseases collectively
      referred to as TDP-43 proteinopathies. These diseases are characterized by the
      presence of cellular aggregates composed of abnormally phosphorylated, N
      terminally truncated and ubiquitinated TDP-43 in the spinal cord and/or brain.
      Recent studies indicate that C-terminal fragments of TDP-43 are aggregation-prone
      and induce cytotoxicity. However, little is known regarding the pathways
      responsible for the degradation of these fragments and how their phosphorylation
      contributes to the pathogenesis of disease. RESULTS: Herein, we established a
      human neuroblastoma cell line (M17D3) that conditionally expresses an enhanced
      green fluorescent protein (GFP)-tagged caspase-cleaved C-terminal TDP-43 fragment
      (GFP-TDP220-414). We report that expression of this fragment within cells leads
      to a time-dependent formation of inclusions that are immunoreactive for both
      ubiquitin and phosphorylated TDP-43, thus recapitulating pathological hallmarks
      of TDP-43 proteinopathies. Phosphorylation of GFP-TDP220-414 renders it resistant
      to degradation and enhances its accumulation into insoluble aggregates.
      Nonetheless, GFP-TDP220-414 inclusions are reversible and can be cleared through
      the ubiquitin proteasome system. Moreover, both Hsp70 and Hsp90 bind to GFP
      TDP220-414 and regulate its degradation. CONCLUSIONS: Our data indicates that
      inclusions formed from TDP-43 C-terminal fragments are reversible. Given that TDP
      43 inclusions have been shown to confer toxicity, our findings have important
      therapeutic implications and suggest that modulating the phosphorylation state of
      TDP-43 C-terminal fragments may be a promising therapeutic strategy to clear TDP
      43 inclusions.

PMID- 20804552
TI  - Protein targets of inflammatory serine proteases and cardiovascular disease.
AB  - Serine proteases are a key component of the inflammatory response as they are
      discharged from activated leukocytes and mast cells or generated through the
      coagulation cascade. Their enzymatic activity plays a major role in the body's
      defense mechanisms but it has also an impact on vascular homeostasis and tissue
      remodeling. Here we focus on the biological role of serine proteases in the
      context of cardiovascular disease and their mechanism(s) of action in determining
      specific vascular and tissue phenotypes. Protease-activated receptors (PARs)
      mediate serine protease effects; however, these proteases also exert a number of
      biological activities independent of PARs as they target specific protein
      substrates implicated in vascular remodeling and the development of
      cardiovascular disease thus controlling their activities. In this review both PAR
      dependent and -independent mechanisms of action of serine proteases are discussed
      for their relevance to vascular homeostasis and structural/functional alterations
      of the cardiovascular system. The elucidation of these mechanisms will lead to a
      better understanding of the molecular forces that control vascular and tissue
      homeostasis and to effective preventative and therapeutic approaches.

PMID- 20804555
TI  - An ovine tracheal explant culture model for allergic airway inflammation.
AB  - BACKGROUND: The airway epithelium is thought to play an important role in the
      pathogenesis of asthmatic disease. However, much of our understanding of airway
      epithelial cell function in asthma has been derived from in vitro studies that
      may not accurately reflect the interactive cellular and molecular pathways active
      between different tissue constituents in vivo. METHODS: Using a sheep model of
      allergic asthma, tracheal explants from normal sheep and allergic sheep exposed
      to house dust mite (HDM) allergen were established to investigate airway mucosal
      responses ex vivo. Explants were cultured for up to 48 h and tissues were stained
      to identify apoptotic cells, goblet cells, mast cells and eosinophils. The
      release of cytokines (IL-1alpha, IL-6 and TNF-alpha) by cultured tracheal
      explants, was assessed by ELISA. RESULTS: The general morphology and epithelial
      structure of the tracheal explants was well maintained in culture although
      evidence of advanced apoptosis within the mucosal layer was noted after culture
      for 48 h. The number of alcian blue/PAS positive mucus-secreting cells within the
      epithelial layer was reduced in all cultured explants compared with pre-cultured
      (0 h) explants, but the loss of staining was most evident in allergic tissues.
      Mast cell and eosinophil numbers were elevated in the allergic tracheal tissues
      compared to naive controls, and in the allergic tissues there was a significant
      decline in mast cells after 24 h culture in the presence or absence of HDM
      allergen. IL-6 was released by allergic tracheal explants in culture but was
      undetected in cultured control explants. CONCLUSIONS: Sheep tracheal explants
      maintain characteristics of the airway mucosa that may not be replicated when
      studying isolated cell populations in vitro. There were key differences
      identified in explants from allergic compared to control airways and in their
      responses in culture for 24 h. Importantly, this study establishes the potential
      for the application of tracheal explant cultures in relevant ex vivo
      investigations on the therapeutic and mechanistic modalities of asthmatic
      disease.

PMID- 20804556
TI  - Therapies for type 2 diabetes: lowering HbA1c and associated cardiovascular risk
      factors.
AB  - OBJECTIVES: To summarize data supporting the effects of antidiabetes agents on
      glucose control and cardiovascular risk factors in patients with type 2 diabetes.
      METHODS: Studies reporting on the effects of antidiabetes agents on glycemic
      control, body weight, lipid levels, and blood pressure parameters are reviewed
      and summarized for the purpose of selecting optimal therapeutic regimens for
      patients with type 2 diabetes. RESULTS: National guidelines recommend the
      aggressive management of cardiovascular risk factors in patients with type 2
      diabetes, including weight loss and achieving lipid and blood pressure treatment
      goals. All antidiabetes pharmacotherapies lower glucose; however, effects on
      cardiovascular risk factors vary greatly among agents. While thiazolidinediones,
      sulfonylureas, and insulin are associated with weight gain, dipeptidyl peptidase
      4 inhibitors are considered weight neutral and metformin can be weight neutral or
      associated with a small weight loss. Glucagon-like peptide-1 receptor agonists
      and amylinomimetics (e.g. pramlintide) result in weight loss. Additionally,
      metformin, thiazolidinediones, insulin, and glucagon-like peptide-1 receptor
      agonists have demonstrated beneficial effects on lipid and blood pressure
      parameters. CONCLUSION: Management of the cardiovascular risk factors experienced
      by patients with type 2 diabetes requires a multidisciplinary approach with
      implementation of treatment strategies to achieve not only glycemic goals but to
      improve and/or correct the underlying cardiovascular risk factors.

PMID- 20804557
TI  - Combined vascular endothelial growth factor-A and fibroblast growth factor 4 gene
      transfer improves wound healing in diabetic mice.
AB  - BACKGROUND: Impaired wound healing in diabetes is related to decreased production
      of growth factors. Hence, gene therapy is considered as promising treatment
      modality. So far, efforts concentrated on single gene therapy with particular
      emphasis on vascular endothelial growth factor-A (VEGF-A). However, as multiple
      proteins are involved in this process it is rational to test new approaches.
      Therefore, the aim of this study was to investigate whether single AAV vector
      mediated simultaneous transfer of VEGF-A and fibroblast growth factor 4 (FGF4)
      coding sequences will improve the wound healing over the effect of VEGF-A in
      diabetic (db/db) mice. METHODS: Leptin receptor-deficient db/db mice were
      randomized to receive intradermal injections of PBS or AAVs carrying beta
      galactosidase gene (AAV-LacZ), VEGF-A (AAV-VEGF-A), FGF-4 (AAV-FGF4-IRES-GFP) or
      both therapeutic genes (AAV-FGF4-IRES-VEGF-A). Wound healing kinetics was
      analyzed until day 21 when all animals were sacrificed for biochemical and
      histological examination. RESULTS: Complete wound closure in animals treated with
      AAV-VEGF-A was achieved earlier (day 19) than in control mice or animals injected
      with AAV harboring FGF4 (both on day 21). However, the fastest healing was
      observed in mice injected with bicistronic AAV-FGF4-IRES-VEGF-A vector (day 17).
      This was paralleled by significantly increased granulation tissue formation,
      vascularity and dermal matrix deposition. Mechanistically, as shown in vitro,
      FGF4 stimulated matrix metalloproteinase-9 (MMP-9) and VEGF receptor-1 expression
      in mouse dermal fibroblasts and when delivered in combination with VEGF-A,
      enhanced their migration. CONCLUSION: Combined gene transfer of VEGF-A and FGF4
      can improve reparative processes in the wounded skin of diabetic mice better than
      single agent treatment.

PMID- 20804558
TI  - Upper-body morbidity following breast cancer treatment is common, may persist
      longer-term and adversely influences quality of life.
AB  - BACKGROUND: Impairments in upper-body function (UBF) are common following breast
      cancer. However, the relationship between arm morbidity and quality of life (QoL)
      remains unclear. This investigation uses longitudinal data to describe UBF in a
      population-based sample of women with breast cancer and examines its relationship
      with QoL. METHODS: Australian women (n=287) with unilateral breast cancer were
      assessed at three-monthly intervals, from six- to 18-months post-surgery (PS).
      Strength, endurance and flexibility were used to assess objective UBF, while the
      Disability of the Arm, Shoulder and Hand questionnaire and the Functional
      Assessment of Cancer Therapy-Breast questionnaire were used to assess self
      reported UBF and QoL, respectively. RESULTS: Although mean UBF improved over
      time, up to 41% of women revealed declines in UBF between six- and 18-months PS.
      Older age, lower socioeconomic position, treatment on the dominant side,
      mastectomy, more extensive lymph node removal and having lymphoedema each
      increased odds of declines in UBF by at least two-fold (p<0.05). Lower baseline
      and declines in perceived UBF between six- and 18-months PS were each associated
      with poorer QoL at 18-months PS (p<0.05). CONCLUSIONS: Significant upper-body
      morbidity is experienced by many following breast cancer treatment, persisting
      longer term, and adversely influencing the QoL of breast cancer survivors.

PMID- 20804559
TI  - The role of adjuvant pelvic radiotherapy in rectal cancer with synchronous liver
      metastasis: a retrospective study.
AB  - BACKGROUND: Synchronous liver metastases are detected in approximately 25% of
      colorectal cancer patients at diagnosis. The rates of local failure and distant
      metastasis are substantial in these patients, even after undergoing aggressive
      treatments including resection of primary and metastatic liver tumors. The
      purpose of this study was to determine whether adjuvant pelvic radiotherapy is
      beneficial for pelvic control and overall survival in rectal cancer patients with
      synchronous liver metastasis after primary tumor resection. METHODS: Among rectal
      cancer patients who received total mesorectal excision (TME) between 1997 and
      2006 at Yonsei University Health System, eighty-nine patients diagnosed with
      synchronous liver metastasis were reviewed. Twenty-seven patients received
      adjuvant pelvic RT (group S + R), and sixty-two patients were managed without RT
      (group S). Thirty-six patients (58%) in group S and twenty patients (74%) in
      group S+R received local treatment for liver metastasis. Failure patterns and
      survival outcomes were analyzed. RESULTS: Pelvic failure was observed in twenty
      five patients; twenty-one patients in group S (34%), and four patients in group
      S+R (15%) (p = 0.066). The two-year pelvic failure-free survival rates (PFFS) of
      group S and group S+R were 64.8% and 80.8% (p = 0.028), respectively, and the two
      year overall survival rates (OS) were 49.1% and 70.4% (p = 0.116), respectively.
      In a subgroup analysis of fifty-six patients who received local treatment for
      liver metastasis, the two-year PFFS were 64.9% and 82.9% (p = 0.05),
      respectively; the two-year OS were 74.1% and 80.0% (p = 0.616) in group S (n =
      36) and group S+R (n = 20), respectively. CONCLUSIONS: Adjuvant pelvic RT
      significantly reduced the pelvic failure rate but its influence on overall
      survival was unclear. Rectal cancer patients with synchronous liver metastasis
      may benefit from adjuvant pelvic RT through an increased pelvic control rate and
      improved quality of life.

PMID- 20804561
TI  - Substitution of exudative trace element losses in burned children.

PMID- 20804560
TI  - Clinical review: Intra-abdominal hypertension: does it influence the physiology
      of prone ventilation?
AB  - Prone ventilation (PV) is a ventilatory strategy that frequently improves
      oxygenation and lung mechanics in critical illness, yet does not consistently
      improve survival. While the exact physiologic mechanisms related to these
      benefits remain unproven, one major theoretical mechanism relates to reducing the
      abdominal encroachment upon the lungs. Concurrent to this experience is
      increasing recognition of the ubiquitous role of intra-abdominal hypertension
      (IAH) in critical illness, of the relationship between IAH and intra-abdominal
      volume or thus the compliance of the abdominal wall, and of the potential
      difference in the abdominal influences between the extrapulmonary and pulmonary
      forms of acute respiratory distress syndrome. The present paper reviews reported
      data concerning intra-abdominal pressure (IAP) in association with the use of PV
      to explore the potential influence of IAH. While early authors stressed the
      importance of gravitationally unloading the abdominal cavity to unencumber the
      lung bases, this admonition has not been consistently acknowledged when PV has
      been utilized. Basic data required to understand the role of IAP/IAH in the
      physiology of PV have generally not been collected and/or reported. No randomized
      controlled trials or meta-analyses considered IAH in design or outcome. While the
      act of proning itself has a variable reported effect on IAP, abundant clinical
      and laboratory data confirm that the thoracoabdominal cavities are intimately
      linked and that IAH is consistently transmitted across the diaphragm--although
      the transmission ratio is variable and is possibly related to the compliance of
      the abdominal wall. Any proning-related intervention that secondarily influences
      IAP/IAH is likely to greatly influence respiratory mechanics and outcomes.
      Further study of the role of IAP/IAH in the physiology and outcomes of PV in
      hypoxemic respiratory failure is thus required. Theories relating inter-relations
      between prone positioning and the abdominal condition are presented to aid in
      designing these studies.

PMID- 20804562
TI  - Anemia and blood transfusion and outcome on the intensive care unit.

PMID- 20804563
TI  - Microarray data analysis in neoadjuvant biomarker studies in estrogen receptor
      positive breast cancer.
AB  - Microarray data have been widely utilized to discover biomarkers predictive of
      response to endocrine therapy in estrogen receptor-positive breast cancer.
      Typically, these data have focused on analyses conducted on the diagnostic
      specimen. However, dynamic temporal changes in gene expression associated with
      treatment may deliver significant improvements to the current generation of
      predictive models. We present and discuss some statistical issues relevant to the
      paper by Taylor and colleagues, who conducted studies to model the prognostic
      potential of gene expression changes that occur after endocrine treatment.

PMID- 20804564
TI  - HIV-1 V3 envelope deep sequencing for clinical plasma specimens failing in
      phenotypic tropism assays.
AB  - BACKGROUND: HIV-1 infected patients for whom standard gp160 phenotypic tropism
      testing failed are currently excluded from co-receptor antagonist treatment. To
      provide patients with maximal treatment options, massively parallel sequencing of
      the envelope V3 domain, in combination with tropism prediction tools, was
      evaluated as an alternative tropism determination strategy. Plasma samples from
      twelve HIV-1 infected individuals with failing phenotyping results were
      available. The samples were submitted to massive parallel sequencing and to
      confirmatory recombinant phenotyping using a fraction of the gp120 domain.
      RESULTS: A cut-off for sequence reads interpretation of 5 to10 times the
      sequencing error rate (0.2%) was implemented. On average, each sample contained 7
      different V3 haplotypes. V3 haplotypes were submitted to tropism prediction
      algorithms, and 4/14 samples returned with presence of a dual/mixed (D/M) tropic
      virus, respectively at 3%, 10%, 11%, and 95% of the viral quasispecies. V3
      tropism prediction was confirmed by gp120 phenotyping, except for two out of 4
      D/M predicted viruses (with 3 and 95%) which were phenotypically R5-tropic. In
      the first case, the result was discordant due to the limit of detection for the
      phenotyping technology, while in the latter case the prediction algorithms were
      not computing the viral tropism correctly. CONCLUSIONS: Although only
      demonstrated on a limited set of samples, the potential of the combined use of
      "deep sequencing + prediction algorithms" in cases where routine gp160 phenotype
      testing cannot be employed was illustrated. While good concordance was observed
      between gp120 phenotyping and prediction of R5-tropic virus, the results suggest
      that accurate prediction of X4-tropic virus would require further algorithm
      development.

PMID- 20804565
TI  - Recent insights into the role of NF-kappaB in ovarian carcinogenesis.
AB  - The NF-kappaBs are a family of ubiquitously expressed transcription factors that
      have been described to be responsible for the establishment of an inflammatory
      response. Studies in the past decade have also demonstrated this family's role in
      the initiation and progression of hematological and solid tumors. Recently,
      research has uncovered a specific role for NF-kappaBs in the development and
      maintenance of ovarian cancer.

PMID- 20804566
TI  - Spatial organization acts on cell signaling: how physical force contributes to
      the development of cancer.
AB  - Cells constantly encounter physical forces and respond to neighbors and
      circulating factors by triggering intracellular signaling cascades that in turn
      affect their behavior. The mechanisms by which cells transduce mechanical signals
      to downstream biochemical changes are not well understood. In their work, Salaita
      and coworkers show that the spatial organization of cell surface receptors is
      crucial for mechanotransduction. Consequently, force modulation that disrupts the
      mechanochemical coupling may represent a critical step in cancerogenesis.

PMID- 20804567
TI  - The Met oncogene and basal-like breast cancer: another culprit to watch out for?
AB  - Recent findings suggest the involvement of the MET oncogene, encoding the
      tyrosine kinase receptor for hepatocyte growth factor, in the onset and
      progression of basal-like breast carcinoma. The expression profiles of basal-like
      tumors - but not those of other breast cancer subtypes - are enriched for gene
      sets that are coordinately over-represented in transcriptional signatures
      regulated by Met. Consistently, tissue microarray analyses have revealed that Met
      immunoreactivity is much higher in basal-like cases of human breast cancer than
      in other tumor types. Finally, mouse models expressing mutationally activated
      forms of Met develop a high incidence of mammary tumors, some of which exhibit
      basal characteristics. The present review summarizes current knowledge on the
      role and activity of Met in basal-like breast cancer, with a special emphasis on
      the correlation between this tumor subtype and the cellular hierarchy of the
      normal mammary gland.

PMID- 20804568
TI  - The missing graphical user interface for genomics.
AB  - The Galaxy package empowers regular users to perform rich DNA sequence analysis
      through a much-needed and user-friendly graphical web interface. See research
      article http://genomebiology.com/2010/11/8/R86 RESEARCH HIGHLIGHT: With the
      advent of affordable and high-throughput DNA sequencing, sequencing is becoming
      an essential component in nearly every genetics lab. These data are being
      generated to probe sequence variations, to understand transcribed, regulated or
      methylated DNA elements, and to explore a host of other biological features
      across the tree of life and across a range of environments and conditions. Given
      this deluge of data, novices and experts alike are facing the daunting challenge
      of trying to analyze the raw sequence data computationally. With so many tools
      available and so many assays to analyze, how can one be expected to stay current
      with the state of the art? How can one be expected to learn to use each tool and
      construct robust end-to-end analysis pipelines, all while ensuring that input
      formats, command-line options, sequence databases and program libraries are set
      correctly? Finally, once the analysis is complete, how does one ensure the
      results are reproducible and transparent for others to scrutinize and study?In an
      article published in Genome Biology, Jeremy Goecks, Anton Nekrutenko, James
      Taylor and the rest of the Galaxy Team (Goecks et al. 1) make a great advance
      towards resolving these critical questions with the latest update to their Galaxy
      Project. The ambitious goal of Galaxy is to empower regular users to carry out
      their own computational analysis without having to be an expert in computational
      biology or computer science. Galaxy adds a desperately needed graphical user
      interface to genomics research, making data analysis universally accessible in a
      web browser, and freeing users from the minutiae of archaic command-line
      parameters, data formats and scripting languages. Data inputs and computational
      steps are selected from dynamic graphical menus, and the results are displayed in
      intuitive plots and summaries that encourage interactive workflows and the
      exploration of hypotheses. The underlying data analysis tools can be almost any
      piece of software, written in any language, but all their complexity is neatly
      hidden inside of Galaxy, allowing users to focus on scientific rather than
      technical questions.

PMID- 20804569
TI  - Mesenchymal stem cells in arthritis: role of bone marrow microenvironment.
AB  - Based on their capacity to suppress immune responses, multipotent mesenchymal
      stromal cells (MSCs) are intensively studied for regenerative medicine. Moreover,
      MSCs are potent immunomodulatory cells that occur through the secretion of
      soluble mediators including nitric oxide, transforming growth factor beta, and
      HLAG5. The MSCs, however, are also able to express inflammatory mediators such as
      prostaglandin E2 or IL-6. MSCs in the bone marrow are in close contact with T
      cells and B cells, and they regulate immunological memory by organizing defined
      numbers of dedicated survival niches for plasma cells and memory T cells in the
      bone marrow. The role of MSCs in arthritis remains controversial - in some
      studies, murine allogeneic MSCs are able to decrease arthritis; in other studies,
      MSCs worsen the local inflammation. A recent paper in Arthritis Research and
      Therapy shows that bone marrow MSCs have decreased osteoblastic potential in
      rheumatoid arthritis, which may be related to chronic inflammation or to loss of
      expression of IL-1 receptor agonist. That article raises the importance of the
      bone marrow microenvironment for MSC biology.

PMID- 20804572
TI  - Right man, right time, right place?--on the time course of the mediator orchestra
      in septic shock.
AB  - Appropriate timing of treatment assumes particular importance in critical care.
      Lange and colleagues recently reported on the time course of the different nitric
      oxide synthase (NOS) isoforms, nitrosative stress, and poly(ADP-ribosylation)
      during Pseudomonas aeruginosa pneumonia-induced ovine septic shock. Initially,
      endothelial NOS expression was increased together with markers of peroxynitrite
      formation, DNA damage, and nuclear factor-kappa-B activation. Later on,
      measurable NOS activity and nitric oxide production resulted mainly from
      inducible NOS activation. These results emphasize the need for long-term, large
      animal studies investigated over days so that future therapeutic interventions
      can be better tailored and matched to the exact time course of the activation of
      the mediator orchestra.

PMID- 20804570
TI  - Breast cancer prognostic classification in the molecular era: the role of
      histological grade.
AB  - Breast cancer is a heterogeneous disease with varied morphological appearances,
      molecular features, behavior, and response to therapy. Current routine clinical
      management of breast cancer relies on the availability of robust clinical and
      pathological prognostic and predictive factors to support clinical and patient
      decision making in which potentially suitable treatment options are increasingly
      available. One of the best-established prognostic factors in breast cancer is
      histological grade, which represents the morphological assessment of tumor
      biological characteristics and has been shown to be able to generate important
      information related to the clinical behavior of breast cancers. Genome-wide
      microarray-based expression profiling studies have unraveled several
      characteristics of breast cancer biology and have provided further evidence that
      the biological features captured by histological grade are important in
      determining tumor behavior. Also, expression profiling studies have generated
      clinically useful data that have significantly improved our understanding of the
      biology of breast cancer, and these studies are undergoing evaluation as improved
      prognostic and predictive tools in clinical practice. Clinical acceptance of
      these molecular assays will require them to be more than expensive surrogates of
      established traditional factors such as histological grade. It is essential that
      they provide additional prognostic or predictive information above and beyond
      that offered by current parameters. Here, we present an analysis of the validity
      of histological grade as a prognostic factor and a consensus view on the
      significance of histological grade and its role in breast cancer classification
      and staging systems in this era of emerging clinical use of molecular
      classifiers.

PMID- 20804573
TI  - Is enough oxygen too much?
AB  - Human cells require O2 for their energy supply, and critical illness can threaten
      the efficient delivery of O2 in accordance with tissue metabolic needs. In the
      accompanying article, Martin and colleagues point out that hypoxia is a normal
      and well-tolerated stress during embryonic development. A better understanding of
      how fetal cells survive these conditions and how adult cells adapt to high
      altitude exposure may provide insight into how these mechanisms might be engaged
      in the treatment of hypoxemic patients. They suggest that 'permissive hypoxia'
      represents a therapeutic possibility. But before we turn down the inspired O2
      levels we should consider the broader effects of hypoxia on tissue repair in
      critical illness.

PMID- 20804574
TI  - Assessing the quantity of pulmonary edema in critically ill children.
AB  - Measuring extravascular lung water may be useful for predicting outcome in adults
      with acute lung injury. The present commentary briefly reviews the potential role
      and limitations of extravascular lung water measurement in critically ill
      children.

PMID- 20804575
TI  - An illuminated view of molecular biology.
AB  - A report on the 18th Annual International Conference on Intelligent Systems for
      Molecular Biology (ISMB) and the 7th Special Interest Group meeting on
      Alternative Splicing, Boston, USA, 9-13 July 2010.

PMID- 20804576
TI  - NGAL: an emerging tool for predicting severity of AKI is easily detected by a
      clinical assay.

PMID- 20804577
TI  - Safer ventilation of the injured lung: one step closer.
AB  - Prevention of iatrogenic injury due to ventilation of a heterogeneous lung
      requires knowledge of dynamic regional events occurring within the tidal cycle.
      Quantitative bedside imaging techniques that are sensitive to regional mechanics
      and tidal events hold potential for information delivery that cannot be realized
      by pressure-volume monitoring alone.

PMID- 20804579
TI  - Elucidating the molecular characteristics of organogenesis in human embryos.
AB  - A transcriptomic analysis of early human organogenesis reveals the molecular
      signature of these processes and provides a valuable resource for identifying and
      comparing crucial regulators of mammalian embryogenesis.

PMID- 20804578
TI  - Bench-to-bedside review: Targeting antioxidants to mitochondria in sepsis.
AB  - Development of organ dysfunction associated with sepsis is now accepted to be due
      at least in part to oxidative damage to mitochondria. Under normal circumstances,
      complex interacting antioxidant defense systems control oxidative stress within
      mitochondria. However, no studies have yet provided conclusive evidence of the
      beneficial effect of antioxidant supplementation in patients with sepsis. This
      may be because the antioxidants are not accumulating in the mitochondria, where
      they are most needed. Antioxidants can be targeted selectively to mitochondria by
      several means. This review describes the in vitro studies and animal models of
      several diseases involving oxidative stress, including sepsis, in which
      antioxidants targeted at mitochondria have shown promise, and the future
      implications for such approaches in patients.

PMID- 20804580
TI  - Predictive, preventive, personalized and participatory medicine: back to the
      future.
AB  - The pioneering work of Jean Dausset on the HLA system established several
      principles that were later reflected in the Human Genome Project and contributed
      to the foundations of predictive, preventive, personalized and participatory (P4)
      medicine. To effectively develop systems medicine, we should take advantage of
      the lessons of the HLA saga, emphasizing the importance of exploring a
      fascinating but mysterious biology, now using systems principles, pioneering new
      technology developments and creating shared biological and information resources.

PMID- 20804581
TI  - Dosage compensation and the global re-balancing of aneuploid genomes.
AB  - Diploid genomes are exquisitely balanced systems of gene expression. The dosage
      compensation systems that evolved along with monosomic sex chromosomes exemplify
      the intricacies of compensating for differences in gene copy number by
      transcriptional regulation.

PMID- 20804582
TI  - Extrinsic regulation of satellite cell specification.
AB  - Cellular commitment during vertebrate embryogenesis is controlled by an interplay
      of intrinsic regulators and morphogenetic signals. These mechanisms recruit a
      subset of cells in the developing organism to become the ancestors of skeletal
      muscle. Signals that control progression through the myogenic lineage converge on
      a battery of hierarchically organized transcription factors which modulate the
      cells to either remain in a primitive state or allow their commitment and
      differentiation into skeletal muscle fibers. A small population of cells will
      retain a largely unspecified state throughout development. Such stem cells, in
      conjunction with more committed myogenic progenitors, form a heterogeneous
      population that colonizes adult skeletal muscle as satellite cells. The satellite
      cell pool is responsible for the remarkable regenerative capacity of skeletal
      muscle. Similar to their counterparts during embryonic development, satellite
      cells are capable of self-renewal and can give rise to myogenic progeny. Impaired
      satellite cell homeostasis has been associated with numerous muscular disorders.
      Due to intense research efforts in the past two decades, the complex biology of
      muscle stem cells has now revealed some of its secrets and new avenues for the
      development of therapeutic molecules have emerged. In the present review we focus
      on the extrinsic mechanisms that control self-renewal, specification and
      differentiation of satellite cells and their significance for the development of
      biologic drugs.

PMID- 20804583
TI  - Role of taurine in the central nervous system.
AB  - Taurine demonstrates multiple cellular functions including a central role as a
      neurotransmitter, as a trophic factor in CNS development, in maintaining the
      structural integrity of the membrane, in regulating calcium transport and
      homeostasis, as an osmolyte, as a neuromodulator and as a neuroprotectant. The
      neurotransmitter properties of taurine are illustrated by its ability to elicit
      neuronal hyperpolarization, the presence of specific taurine synthesizing enzyme
      and receptors in the CNS and the presence of a taurine transporter system.
      Taurine exerts its neuroprotective functions against the glutamate induced
      excitotoxicity by reducing the glutamate-induced increase of intracellular
      calcium level, by shifting the ratio of Bcl-2 and Bad ratio in favor of cell
      survival and by reducing the ER stress. The presence of metabotropic taurine
      receptors which are negatively coupled to phospholipase C (PLC) signaling pathway
      through inhibitory G proteins is proposed, and the evidence supporting this
      notion is also presented.

PMID- 20804584
TI  - Glutamate receptor-mediated taurine release from the hippocampus during oxidative
      stress.
AB  - BACKGROUND: Hippocampal slices swell and release taurine during oxidative stress.
      The influence of cellular signalling pathways on this process is unclear.
      Glutamate signalling can facilitate volume regulation in other CNS preparations.
      Therefore, we hypothesize activation of taurine release by oxidative stress
      results from tissue swelling and is coupled to activation of glutamate receptors.
      METHODS: Rat hippocampi were incubated at room temperature for 2 hr in artificial
      cerebrospinal fluid (aCSF) equilibrated with 95% O2 plus 5% CO2. For some slices,
      1 mM taurine was added to the aCSF to maintain normal tissue taurine content.
      Slices then were perfused with aCSF at 35 degrees C and baseline data recorded
      before 2 mM H2O2 was added. For some studies, mannitol or inhibitors of glutamate
      receptors or the volume-regulated anion channel (VRAC) were added before and
      during H2O2 treatment. The intensity of light transmitted through the slice (the
      intrinsic optical signal, IOS) was determined at 1-min intervals. Samples of
      perfusate were collected at 2-min intervals and amino acid contents determined by
      HPLC. Data were analyzed by repeated measures ANOVA and post hoc Dunnett's test
      with significance indicated for p<0.05. RESULTS: IOS of slices prepared without
      taurine treatment increased significantly by 3.3+/-1.3% (mean+/-SEM) during
      oxidative stress. Little taurine was detected in the perfusate of these slices
      and the rate of taurine efflux did not change during H2O2 exposure. The alpha
      amino-3-hydroxyl-5-methyl-4-isoxazole-propionate antagonist, 25 microM CNQX, but
      not the N-methyl-D-aspartate (NMDA) receptor antagonist, 10 microM MK-801,
      inhibited the increase in IOS during H2O2 treatment. Taurine-treated slices
      exposed to H2O2 showed no change in IOS; however, taurine efflux increased by
      335+/-178%. When these slices were perfused with hypertonic aCSF (350 mOsm) or
      exposed to the VRAC inhibitor, 20 microM DCPIB, no increase in the taurine efflux
      rate was observed during H2O2 exposure. Taurine-treated slices perfused with 10
      microM MK-801 during H2O2 exposure showed a 4.6+/-1.9% increase in IOS but no
      increase in the taurine efflux rate. CONCLUSIONS: Taurine efflux via VRAC is
      critical for volume regulation of hippocampal slices exposed to oxidative stress.
      This increased taurine efflux does not result from direct activation of the
      taurine release pathway by H2O2. NMDA receptor activation plays an important role
      in taurine release during oxidative stress.

PMID- 20804585
TI  - Taurine regulates insulin release from pancreatic beta cell lines.
AB  - BACKGROUND: Pancreatic beta-cells release insulin via an electrogenic response
      triggered by an increase in plasma glucose concentrations. The critical plasma
      glucose concentration has been determined to be approximately 3 mM, at which time
      both insulin and GABA are released from pancreatic beta-cells. Taurine, a beta
      sulfonic acid, may be transported into cells to balance osmotic pressure. The
      taurine transporter (TauT) has been described in pancreatic tissue, but the
      function of taurine in insulin release has not been established. Uptake of
      taurine by pancreatic beta-cells may alter membrane potential and have an effect
      on ion currents. If taurine uptake does alter beta-cell current, it might have an
      effect on exocytosis of cytoplasmic vesicle. We wished to test the effect of
      taurine on regulating release of insulin from the pancreatic beta-cell. METHODS:
      Pancreatic beta-cell lines Hit-TI5 (Syrian hamster) and Rin-m (rat insulinoma)
      were used in these studies. Cells were grown to an 80% confluence on uncoated
      cover glass in RPMI media containing 10% fetal horse serum. The cells were then
      adapted to a serum-free, glucose free environment for 24 hours. At that time, the
      cells were treated with either 1 mM glucose, 1 mM taurine, 1 mM glucose + 1 mM
      taurine, 3 mM glucose, or 3 mM glucose + 1 mM taurine. The cells were examined by
      confocal microscopy for cytoplasmic levels of insulin. RESULTS: In both cell
      lines, 1 mM glucose had no effect on insulin levels and served as a control.
      Cells starved of glucose had a significant reduction (p<0.001) in the level of
      insulin, but this level was significantly higher than all other treatments. As
      expected, the 3 mM glucose treatment resulted in a statistically lower (p<0.001)
      insulin level than control cells. Interestingly, 1 mM taurine also resulted in a
      statistically lower level of insulin (p<0.001) compared to controls when either
      no glucose or 1 mM glucose was present. Cells treated with 1 mM taurine plus 3 mM
      glucose showed a level of insulin similar to that of 3 mM glucose alone.
      CONCLUSIONS: Taurine administration can alter the electrogenic response in beta
      cell lines, leading to a change in calcium homeostasis and a subsequent decrease
      in intracellular insulin levels. The consequence of these actions could represent
      a method of increasing plasma insulin levels leading to a decrease in plasma
      glucose levels.

PMID- 20804586
TI  - Neuroprotection by taurine in ethanol-induced apoptosis in the developing
      cerebellum.
AB  - BACKGROUND: Acute ethanol administration leads to massive apoptotic
      neurodegeneration in the developing central nervous system. We studied whether
      taurine is neuroprotective in ethanol-induced apoptosis in the mouse cerebellum
      during the postnatal period. METHODS: The mice were divided into three groups:
      ethanol-treated, ethanol+taurine-treated and controls. Ethanol (20% solution) was
      administered subcutaneously at a total dose of 5 g/kg (2.5 g/kg at time 1 h and
      2.5 g/kg at 3 h) to the ethanol and ethanol+taurine groups. The ethanol+taurine
      group also received two injections of taurine (1 g/kg each, at time zero and at 4
      h). To estimate apoptosis, immunostaining for activated caspase-3 and TUNEL
      staining were made in the mid-sagittal sections containing lobules I-X of the
      cerebellar vermis at 12 or 8 hours after the first taurine injection. Changes in
      the blood taurine level were monitored at each hour by reverse-phase high
      performance liquid chromatography (HPLC). RESULTS: Ethanol administration induced
      apoptosis of Purkinje cells on P4 in all cerebellar lobules, most extensively in
      lobules IX and X, and on P7 increased the number of activated caspase-3
      immunoreactive and TUNEL-positive cells in the internal layer of the cerebellum.
      Administration of taurine significantly decreased the number of activated caspase
      3-immunoreactive and TUNEL-positive cells in the internal layer of the cerebellum
      on P7, but had no effect on Purkinje cells in P4 mice. The high initial taurine
      concentration in blood of the ethanol+taurine group diminished dramatically
      during the experiment, not being different at 13 h from that in the controls.
      CONCLUSIONS: We conclude that the neuroprotective action of taurine is not
      straightforward and seems to be different in different types of neurons and/or
      requires prolonged maintenance of the high taurine concentration in blood plasma.

PMID- 20804587
TI  - Effects of zinc ex vivo on taurine uptake in goldfish retinal cells.
AB  - BACKGROUND: Taurine and zinc exert neurotrophic effects in the central nervous
      system. Current studies demonstrate that Na+/Cl- dependent neurotransmitter
      transporters, similar to that of taurine, are modulated by micromolar
      concentrations of zinc. This study examined the effect of zinc sulfate ex vivo on
      [3H]taurine transport in goldfish retina. METHODS: Isolated cells were incubated
      in Ringer with zinc (0.1-100 microM). Taurine transport was done with 50 nM
      [3H]taurine or by isotopic dilution with taurine (0.001-1 mM) and 50 nM
      [3H]taurine. RESULTS: Zinc reduced the capacity of taurine transport without
      changes in affinity, and caused a noncompetitive inhibition of high affinity
      taurine transport, with an EC50= 0.072 microM. The mechanism by which zinc
      affects taurine transport is unknown at the present. CONCLUSIONS: There may be a
      binding site of zinc in the transporter that affects union or translocation of
      taurine, or possibly the formation of taurine-zinc complexes, rather than free
      zinc, could affect the operation of the transporter.

PMID- 20804588
TI  - Pharmacological characterization of GABAA receptors in taurine-fed mice.
AB  - BACKGROUND: Taurine is one of the most abundant free amino acids especially in
      excitable tissues, with wide physiological actions. Chronic supplementation of
      taurine in drinking water to mice increases brain excitability mainly through
      alterations in the inhibitory GABAergic system. These changes include elevated
      expression level of glutamic acid decarboxylase (GAD) and increased levels of
      GABA. Additionally we reported that GABAA receptors were down regulated with
      chronic administration of taurine. Here, we investigated pharmacologically the
      functional significance of decreased / or change in subunit composition of the
      GABAA receptors by determining the threshold for picrotoxin-induced seizures.
      Picrotoxin, an antagonist of GABAA receptors that blocks the channels while in
      the open state, binds within the pore of the channel between the beta2 and beta3
      subunits. These are the same subunits to which GABA and presumably taurine binds.
      METHODS: Two-month-old male FVB/NJ mice were subcutaneously injected with
      picrotoxin (5 mg kg-1) and observed for a) latency until seizures began, b)
      duration of seizures, and c) frequency of seizures. For taurine treatment, mice
      were either fed taurine in drinking water (0.05%) or injected (43 mg/kg) 15 min
      prior to picrotoxin injection. RESULTS: We found that taurine-fed mice are
      resistant to picrotoxin-induced seizures when compared to age-matched controls,
      as measured by increased latency to seizure, decreased occurrence of seizures and
      reduced mortality rate. In the picrotoxin-treated animals, latency and duration
      were significantly shorter than in taurine-treated animas. Injection of taurine
      15 min before picrotoxin significantly delayed seizure onset, as did chronic
      administration of taurine in the diet. Further, taurine treatment significantly
      increased survival rates compared to the picrotoxin-treated mice. CONCLUSIONS: We
      suggest that the elevated threshold for picrotoxin-induced seizures in taurine
      fed mice is due to the reduced binding sites available for picrotoxin binding due
      to the reduced expression of the beta subunits of the GABAA receptor. The delayed
      effects of picrotoxin after acute taurine injection may indicate that the two
      molecules are competing for the same binding site on the GABAA receptor. Thus,
      taurine-fed mice have a functional alteration in the GABAergic system. These
      include: increased GAD expression, increased GABA levels, and changes in subunit
      composition of the GABAA receptors. Such a finding is relevant in conditions
      where agonists of GABAA receptors, such as anesthetics, are administered.

PMID- 20804589
TI  - Taurine regulation of short term synaptic plasticity in fragile X mice.
AB  - BACKGROUND: Fragile X Syndrome is the most common known genetic cause of autism.
      The Fmr1-KO mouse, lacks the fragile X mental retardation protein (FMRP), and is
      used as a model of the syndrome. The core behavioral deficits of autism may be
      conceptualized either as excessive adherence to patterns as seen in repetitive
      actions and aberrant language, or as insensitivity to subtle but socially
      important changes in patterns. The hippocampus receives information from the
      entorhinal cortex and plays a crucial role in the processing of patterned
      information. To gain more insight into the physiological function of FMRP and the
      neuronal mechanisms underlying fragile X syndrome, we examined the
      electrophysiological response of the hippocampus to pair pulse stimulation as a
      measure of patterned information processing and how it is affected in the Fmr1-KO
      mouse. METHODS: In this study, we used paired-pulse stimulation of the afferent
      perforant path and recorded from the CA1 region of the hippocampus. Two-month-old
      FVB/NJ male mice and age-matched Fmr1-KO mice were used in this study.
      Hippocampal slices were prepared, equilibrated in artificial cerebrospinal fluid
      (aCSF), and excitatory post synaptic potentials (EPSPs) measured by stimulating
      the perforant path of the dentate gyrus (DG) while recording from the molecular
      layer of CA1. Stimulation occurred by setting current and pulse width to evoke a
      fixed percentage of maximal EPSP amplitude. This stimulation paradigm allowed us
      to examine the processing capabilities of the hippocampus as a function of
      increasing interstimulus intervals (ISI) and how taurine, a GABAA receptor
      agonist, affects such information processing. RESULTS: We found that hippocampal
      slices from wild type (WT) showed pair-pulse facilitation at ISI of 100-300 ms
      whereas slices from Fmr1-KO brains showed a consistent pair-pulse depression at a
      comparable ISI. Addition of 10 muM taurine to WT slices resulted in a drastic
      decrease of the peak response to the second stimulus, resulting in an initial
      depression at 100 ms ISI followed by potentiation at higher ISI (150 ms and
      above). In the presence of taurine, the amplitude of the second response remained
      significantly lower than in its absence. Fmr1-KO mice however, were completely
      insensitive to taurine application and pair-pulse stimulation always resulted in
      a depression of the response to the second stimulus. CONCLUSIONS: Previously we
      reported that Fmr1-KO mice have reduced beta subunits of the GABAA receptors. We
      also showed as well as others that taurine acts as an agonist or a modulator for
      GABAA receptors. Therefore, the insensitivity of Fmr1-KO slices to taurine
      application could be due to the reduced binding sites on the GABAA receptors in
      the Fmr1-KO mice.

PMID- 20804590
TI  - Comparative study of the binding characteristics to and inhibitory potencies
      towards PARP and in vivo antidiabetogenic potencies of taurine, 3-aminobenzamide
      and nicotinamide.
AB  - BACKGROUND: Poly(ADP-ribose) is a NAD+-requiring, DNA-repairing, enzyme playing a
      central role in pancreatic beta-cell death and in the development of endothelial
      dysfunction in humans and experimental animals. PARP activation is also relevant
      to the development of complications of diabetes. Hence, agents capable of
      inhibiting PARP may be useful in preventing the development of diabetes and in
      slowing down complications of diabetes. METHODS: PARP inhibition was assessed
      with a colorimetric assay kit. Molecular docking studies on the active site of
      PARP were conducted using the crystalline structure of the enzyme available as
      Protein Data Bank Identification No. 1UK1. Type 2 diabetes was induced in male
      Sprague-Dawley rats with streptozotocin (STZ, 60 mg/kg, i.p.). The test compounds
      (3-aminobenzamide = 3-AB, nicotinamide = NIC, taurine = TAU) were given by the
      i.p. route 45 min before STZ at 2.4 mM/kg (all three compounds) or 1.2 and 3.6
      mM/kg (only NIC and TAU). Blood samples were collected at 24 hr after STZ and
      processed for their plasma. The plasma samples were used to measure glucose,
      insulin, cholesterol, triglycerides, malondialdehyde, nitric oxide, and
      glutathione levels using reported methods. RESULTS: 3-AB, NIC and TAU were able
      to inhibit PARP, with the inhibitory potency order being 3-AB>NIC> or =TAU.
      Molecular docking studies at the active site of PARP showed 3-AB and NIC to
      interact with the binding site for the nicotinamide moiety of NAD+ and TAU to
      interact with the binding site for the adenine moiety of NAD+. While STZ-induced
      diabetes elevated all the experimental parameters examined and lowered the
      insulin output, a pretreatment with 3-AB, NIC or TAU reversed these trends to a
      significant extent. At a dose of 2.4 mm/kg, the protective effect decreased in
      the approximate order 3-AB>NIC> or =TAU. The attenuating actions of both NIC and
      TAU were dose-related except for the plasma lipids since NIC was without a
      significant effect at all doses tested. CONCLUSIONS: At equal molar doses, 3-AB
      was generally more potent than either TAU or NIC as an antidiabetogenic agent,
      but the differences were not as dramatic as would have been predicted from their
      differences in PARP inhibitory potencies. NIC and TAU demonstrated dose-related
      effects, which in the case of TAU were only evident at doses > or =2.4 mM/kg. The
      present results also suggest that in the case of NIC and TAU an increase in dose
      will enhance the magnitude of their attenuating actions on diabetes-related
      biochemical alterations to that achieved with a stronger PARP inhibitor such as 3
      AB. Hence, dosing will play a critical role in clinical studies assessing the
      merits of NIC and TAU as diabetes-preventing agents.

PMID- 20804591
TI  - Taurine protection of PC12 cells against endoplasmic reticulum stress induced by
      oxidative stress.
AB  - BACKGROUND: Taurine is a free amino acid present in high concentrations in a
      variety of organs of mammalians. As an antioxidant, taurine has been found to
      protect cells against oxidative stress, but the underlying mechanism is still
      unclear. METHODS: In this report, we present evidence to support the conclusion
      that taurine exerts a protective function against endoplasmic reticulum (ER)
      stress induced by H2O2 in PC 12 cells. Oxidative stress was introduced by
      exposure of PC 12 cells to 250 uM H2O2 for 4 hours. RESULTS: It was found that
      the cell viability of PC 12 cells decreased with an increase of H2O2
      concentration ranging from approximately 76% cell viability at 100 uM H2O2 down
      to 18% at 500 uM H2O2. At 250 uM H2O2, cell viability was restored to 80% by
      taurine at 25 mM. Furthermore, H2O2 treatment also caused a marked reduction in
      the expression of Bcl-2 while no significant change of Bax was observed.
      Treatment with taurine restored the reduced expression of Bcl-2 close to the
      control level without any obvious effect on Bax. Furthermore, taurine was also
      found to suppress up-regulation of GRP78, GADD153/CHOP and Bim induced by H2O2,
      suggesting that taurine may also exert a protective function against oxidative
      stress by reducing the ER stress. CONCLUSION: In summary, taurine was shown to
      protect PC12 cells against oxidative stress induced by H2O2. ER stress was
      induced by oxidative stress and can be suppressed by taurine.

PMID- 20804592
TI  - Protection of taurine and granulocyte colony-stimulating factor against
      excitotoxicity induced by glutamate in primary cortical neurons.
AB  - BACKGROUND: Both taurine, an inhibitory neurotransmitter and granulocyte colony
      stimulating factor (G-CSF), a growth factor, possess neuroprotective and
      neurotrophic properties in vitro. However, the mechanisms of their underlying
      neuroprotective effects are not fully understood. METHODS: In the present study,
      we investigated the potential protective benefits of taurine, G-CSF and the
      combination of taurine and G-CSF against excitotoxicity induced by glutamate in
      primary cortical neuronal cultures. RESULTS: 25 mM taurine, 25 ng/ml G-CSF and
      the combination of 25 mM taurine and 25 ng/ml G-CSF showed a protective effect
      reaching 75%, 75% and 88%, respectively. Furthermore, taurine exerted its
      protective effect through down-regulation of expression of GRP 78, CHOP, Bim and
      caspase 12. CONCLUSION: The results showed that all of these treatments, taurine,
      G-CSF and the combination of taurine and G-CSF, protected primary cortical
      neurons against excitotoxicity induced by glutamate. ER stress is suppressed by
      taurine after glutamate toxicity.

PMID- 20804594
TI  - Physiological roles of taurine in heart and muscle.
AB  - Taurine (aminoethane sulfonic acid) is an ubiquitous compound, found in very high
      concentrations in heart and muscle. Although taurine is classified as an amino
      acid, it does not participate in peptide bond formation. Nonetheless, the amino
      group of taurine is involved in a number of important conjugation reactions as
      well as in the scavenging of hypochlorous acid. Because taurine is a fairly inert
      compound, it is an ideal modulator of basic processes, such as osmotic pressure,
      cation homeostasis, enzyme activity, receptor regulation, cell development and
      cell signalling. The present review discusses several physiological functions of
      taurine. First, the observation that taurine depletion leads to the development
      of a cardiomyopathy indicates a role for taurine in the maintenance of normal
      contractile function. Evidence is provided that this function of taurine is
      mediated by changes in the activity of key Ca2+ transporters and the modulation
      Ca2+ sensitivity of the myofibrils. Second, in some species, taurine is an
      established osmoregulator, however, in mammalian heart the osmoregulatory
      function of taurine has recently been questioned. Third, taurine functions as an
      indirect regulator of oxidative stress. Although this action of taurine has been
      widely discussed, its mechanism of action is unclear. A potential mechanism for
      the antioxidant activity of taurine is discussed. Fourth, taurine stabilizes
      membranes through direct interactions with phospholipids. However, its inhibition
      of the enzyme, phospholipid N-methyltransferase, alters the phosphatidylcholine
      and phosphatidylethanolamine content of membranes, which in turn affects the
      function of key proteins within the membrane. Finally, taurine serves as a
      modulator of protein kinases and phosphatases within the cardiomyocyte. The
      mechanism of this action has not been studied. Taurine is a chemically simple
      compound, but it has profound effects on cells. This has led to the suggestion
      that taurine is an essential or semi-essential nutrient for many mammals.

PMID- 20804595
TI  - Cardiac and skeletal muscle abnormality in taurine transporter-knockout mice.
AB  - Taurine, a sulfur-containing beta-amino acid, is highly contained in heart and
      skeletal muscle. Taurine has a variety of biological actions, such as ion
      movement, calcium handling and cytoprotection in the cardiac and skeletal
      muscles. Meanwhile, taurine deficiency leads various pathologies, including
      dilated cardiomyopathy, in cat and fox. However, the essential role of taurine
      depletion on pathogenesis has not been fully clarified. To address the
      physiological role of taurine in mammalian tissues, taurine transporter-(TauT-)
      knockout models were recently generated. TauTKO mice exhibited loss of body
      weight, abnormal cardiac function and the reduced exercise capacity with tissue
      taurine depletion. In this chapter, we summarize pathological profile and
      histological feature of heart and skeletal muscle in TauTKO mice.

PMID- 20804593
TI  - Protective action of taurine, given as a pretreatment or as a posttreatment,
      against endotoxin-induced acute lung inflammation in hamsters.
AB  - To assess the effect of taurine on lipopolysaccharide (LPS)-induced lung
      inflammation, oxidative stress and apoptosis, female Golden Syrian hamsters were
      intratracheally instilled with bacterial LPS (0.02 mg in phosphate buffered
      saline (PBS) pH 7.4), before or after a 3-day intraperitoneal treatment with a
      single dose of taurine (50 mg/kg/day in PBS pH 7.4), and bronchoalveolar lavage
      fluid (BALF) and lung tissue samples were collected at 24 hr after the last
      treatment. In comparison to BALF samples from animals receiving only PBS pH 7.4,
      and serving as controls, those of LPS-stimulated animals exhibited a higher count
      of both total leukocytes and neutrophils and increased expression of tumor
      necrosis factor receptor 1. In comparison to lungs from control animals, those
      from LPS-treated animals showed increased cellular apoptosis, lipid peroxidation,
      decreased glutathione levels, altered activities of antioxidant enzymes
      (catalase, glutathione peroxidase, superoxide dismutase) and focal inflammation
      confined to the parenchyma. A treatment with taurine was found to significantly
      attenuate all these alterations, with the protection being, in all instances,
      greater when given before rather than after LPS. The present results suggest that
      taurine is endowed with antiinflammatory and antioxidant properties that are
      protective in the lung against the deleterious actions of Gram negative bacterial
      endotoxin.

PMID- 20804596
TI  - Low cardiovascular risks in the middle aged males and females excreting greater
      24-hour urinary taurine and magnesium in 41 WHO-CARDIAC study populations in the
      world.
AB  - BACKGROUND: Since taurine (T) administration was proven to decrease blood
      pressure (BP) and stroke mortality in stroke-prone spontaneously hypertension
      rates (SHRSP) in the 1980's and our WHO-coordinated CARDIAC (Cardiovascular
      Diseases and Alimentary Comparison) Study demonstrated that among 5 diet-related
      factors, namely total cholesterol (T-Cho), body mass index (BMI), sodium (Na),
      magnesium (M), and T to creatinine (Cr) ratio in 24-hour urine (24U), both T/Cr
      and M/Cr were inversely related to coronary heart disease mortalities in males
      and females and T/Cr was inversely related to stroke mortalities in males and
      females. We further analyzed the associations of individual T/Cr and M/Cr levels
      to cardiovascular risks in the present study. METHOD: From WHO-CARDIAC Study
      populations, 61 populations of 25 countries in the world, Japanese populations
      with obviously higher 24U T excretion because of their common fish eating custom
      and the other populations in which both data of T and M were not available were
      excluded and the data of 3960 individuals from 41 WHO-CARDIAC Study populations
      were used for the following analyses. RESULTS: The means of 24U T/Cr and M/Cr
      ratios in total individual data were 639.4 and 82.8, respectively. The average of
      BMI, systolic and diastolic blood pressure (SBP, DBP), T-Cho and atherogenic
      index (AI) in the individuals with more than the means of T/Cr or M/Cr were
      significantly lower than those of individuals with less than the means. The
      CARDIAC Study participants were divided into the following 4 groups by these
      means: A (T/Cr and M/Cr > or = mean), B (T/Cr > or = mean, M/Cr < mean), C (T/Cr
      < mean, M/Cr > or = mean), D (T/Cr and M/Cr < mean). The group A showed
      significantly lower values compared with the group D in BMI, SBP, DBP, T-Cho, and
      AI. CONCLUSIONS: Cardiovascular risks were proven to be highly significantly
      lower in individuals who were excreting both 24U T and M, more than the averages
      despite differences in ethnicity and genetic background. Since T and M are
      biomarkers for seafood, vegetables, soy, nuts, milk, etc., dietary custom to eat
      these food sources could be recommended for cardiovascular disease prevention.

PMID- 20804598
TI  - A role for taurine in mitochondrial function.
AB  - The mitochondrial pH gradient across the inner-membrane is stabilised by
      buffering of the matrix. A low-molecular mass buffer compound has to be localised
      in the matrix to maintain its alkaline pH value. Taurine is found ubiquitously in
      animal cells with concentrations in the millimolar range and its pKa value is
      determined to 9.0 (25 degrees C) and 8.6 (37 degrees C), respectively.
      Localisation of such a low-molecular buffer in the mitochondrial matrix,
      transforms the matrix into a biochemical reaction chamber for the important
      matrix-localised enzyme systems. Three acyl-CoA dehydrogenase enzymes, which are
      pivotal for beta-oxidation of fatty acids, are demonstrated to have optimal
      activity in a taurine buffer. By application of the model presented, taurine
      depletion caused by hyperglycemia could provide a link between mitochondrial
      dysfunction and diabetes.

PMID- 20804597
TI  - High sugar intake exacerbates cardiac reperfusion injury in perinatal taurine
      depleted adult rats.
AB  - Perinatal taurine depletion and high sugar diets blunted baroreflex function and
      heightens sympathetic nerve activity in adult rats. Cardiac ischemia/reperfusion
      also produces these disorders and taurine treatment appears to improve these
      effects. This study tests the hypothesis that perinatal taurine exposure
      predisposes recovery from reperfusion injury in rats on either a basal or high
      sugar diet. Female Sprague-Dawley rats were fed normal rat chow with 3% beta
      alanine (taurine depletion, TD), 3% taurine (taurine supplementation, TS) or
      water alone (control, C) from conception to weaning. Male offspring were fed
      normal rat chow and water containing 5% glucose (G) or water alone (W) throughout
      the experiment. At 7-8 weeks of age, all rats were anesthetized and their trachea
      clamped until cardiac arrest occurred and mean arterial pressure fell below 60 mm
      Hg. The clamp was immediately released and cardiopulmonary resuscitation was
      performed with cardiac function returning within 4 min. Twenty-four hours later,
      arterial pressure, heart rate, and baroreflex function were measured in conscious
      and one day later in anesthetized conditions. Basic blood chemistry and
      circulating markers of cardiac injury were also measured. Baroreflex sensitivity
      was depressed moderately in CG and TDW, and severely in TDG. TSW displayed
      increased baroreflex and high sugar intake returned it to CW. Sympathetic nerve
      activity increased and parasympathetic decreased in TDW but not TSW and these
      effects were exacerbated sharply in TDG and slightly in TSG. Arterial pressure
      and heart rate increased in all groups but to a lesser degree in TDG. Plasma
      aspartate aminotransferase increased in all groups except TSW, but the increase
      was nearly 3X greater in TDG vs. any other group. Creatine kinase-MB increased in
      all groups except TSG and was far greater in TD than other groups. Troponin-T and
      brain natriuretic peptide were greatly increased in TDG compared to all other
      groups. Thus, perinatal taurine depletion increases injury from cardiac
      ischemia/reperfusion, and in adult rats on a high sugar diet, these effects are
      greatly exacerbated.

PMID- 20804599
TI  - Taurine and proliferation of lymphocytes in physically restrained rats.
AB  - BACKGROUND: Taurine is present in lymphocytes and seems to modulate certain
      immune cell functions. Among the effects of taurine on these cells are protection
      against antioxidants and regulation of inflammatory aspects of the immune
      response. Stress affects antigen presentation, traffic and proliferation of
      leukocytes, as well as antibody and cytokine secretion. The purposes of this
      study were to explore the possible direct effects of taurine concentrations on
      lymphoproliferation and interleukins levels in control and in physical restrained
      rats. METHODS: Lymphocytes of male Sprague-Dawley rats, stressed by physical
      restrain and controls (5 h per day for 5 days) were isolated from blood by
      Histopaque (1077 g/l) and differential adhesion to plastic, and then cultured (72
      h) in the presence of different concentrations of taurine (0.5-50 mM), beta
      alanine (0.5-50 mM), or both, without or with the T cells mitogen, concanavalin
      A. Plasma and lymphocytes levels of pro-inflammatory interleukin-1beta and anti
      inflammatory interleukin-10 were respectively measured by Pierce Endogen rat
      ELISA Kits. Taurine in plasma and in lymphocytes were determined by HPLC.
      RESULTS: Lymphoproliferation of resting cells significantly decreased in the
      presence of 3 and 6 mM taurine and increased up to control level at 12 mM
      taurine. In concanavalin A-activated lymphocytes, the effect of taurine was
      greater. beta-alanine increased lymphoproliferation in a bell shaped dose
      dependent manner and decreased it in activated lymphocytes but in a lower
      magnitude. In combination, beta-alanine impaired the effect of taurine at 3 and 6
      mM. After restriction, no change in lymphoproliferation was observed at different
      concentrations of the amino acids without or with concanavalin A, although pro
      inflammatory interleukin and taurine in plasma and in lymphocytes significantly
      increased. CONCLUSIONS: Taurine affects lymphoproliferation in control rats,
      following a dose-dependent manner, an effect that might involve its transport
      into the cells. Elevation of interleukin-1beta produced in stressed rats by
      physical restrain could seriously affect the immune balance, whereas taurine
      increase might be protective. These results suggest that taurine and taurine
      transport play a role in lymphoproliferation. In addition, modifications of
      taurine system in lymphocytes take place during restriction stress.

PMID- 20804600
TI  - Effect of beta-alanine treatment on mitochondrial taurine level and 5
      taurinomethyluridine content.
AB  - BACKGROUND: The beta-amino acid, taurine, is a nutritional requirement in some
      species. In these species, the depletion of intracellular stores of taurine leads
      to the development of severe organ dysfunction. The basis underlying these
      defects is poorly understood, although there is some suggestion that oxidative
      stress may contribute to the abnormalities. Recent studies indicate that taurine
      is required for normal mitochondrial protein synthesis and normal electron
      transport chain activity; it is known that defects in these events can lead to
      severe mitochondrial oxidative stress. The present study examines the effect of
      taurine deficiency on the first step of mitochondrial protein synthesis
      regulation by taurine, namely, the formation of taurinomethyluridine containing
      tRNA. METHODS: Isolated rat cardiomyocytes were rendered taurine deficient by
      incubation with medium containing the taurine transport inhibitor, beta-alanine.
      The time course of cellular and mitochondrial taurine depletion was measured. The
      primer extension method was employed to evaluate the effect of beta-alanine
      treatment on taurinomethyluridine content of tRNALeu. The protein levels of ND6
      were also determined by Western blot analysis. RESULTS: beta-alanine caused a
      time-dependent decrease in cellular taurine content, which were reduced in half
      after 48 hrs of incubation. The amount of taurine in the mitochondria was
      considerably less than that in the cytosol and was unaffected by beta-alanine
      treatment. Approximately 70% of the tRNALeu in the untreated cell lacked
      taurinomethyluridine and these levels were unchanged following beta-alanine
      treatment. Protein content of ND6, however, was significantly reduced after 48
      hours incubation with beta-alanine. CONCLUSIONS: The taurine levels of the
      cytosol and the mitochondria are not directly coupled. The beta-alanine-mediated
      reduction in taurine levels is too small to affect taurinomethyluridine levels.
      Nonetheless, it interferes with mitochondrial protein synthesis, as exemplified
      by a decrease in ND6 protein content. Thus, beta-alanine does not cause
      alterations in mitochondrial protein synthesis through the lowering of taurine
      levels.

PMID- 20804601
TI  - Taurine reduces ER stress in C. elegans.
AB  - BACKGROUND: ER stress is a strong indicator of whether or not a cell is
      undergoing physiological stress. C. elegans is a practical system of
      characterizing the effect of ER stress at the in vivo or organismal level.
      METHODS: This study characterized taurine's anti-ER stress potential employing
      western blotting on ER stress markers and assays of motility, lifespan
      comparison, and fecundity measurement. RESULTS: When treated with tunicamycin, C.
      elegans showed the typical ER stress symptoms. It showed a higher expression of
      hsp-70 and skn-1 than the non-treated control. Survivorship significantly
      decreased under tunicamycin treatment, and the offspring number also decreased.
      During the synchronized culture under ER stress conditions, the C. elegans showed
      early signs of aging especially between L3 and L4 within their life span, along
      with lowered motility. The worms, however, showed a positive response to the
      taurine treatment under ER stress conditions. CONCLUSIONS: When C. elegans were
      treated with taurine before or after the tunicamycin treatment, they showed a
      less severe level of ER stress, including an enhanced survivorship, increased
      motility, and augmented fecundity. Taken together, these results strongly
      indicate that taurine works positively to cope with ER stress from the organismal
      perspective.

PMID- 20804602
TI  - Effect of taurine chloramine on the production of matrix metalloproteinases
      (MMPs) in adiponectin- or IL-1beta-stimulated fibroblast-like synoviocytes.
AB  - BACKGROUND: Adiponectin greatly stimulated the expression of matrix
      metalloproteinases (MMPs) in fibroblast-like synoviocytes (FLSs) as did IL-1beta.
      We wondered whether taurine chloramine (TauCl) inhibits the production of MMPs
      stimulated by adiponectin in the same pattern as by IL-1beta stimulation in vitro
      METHODS: Synovial cells from rheumatoid arthritis (RA) patients were treated with
      adiponectin or interleukin (IL)-1beta for 24 hr in the presence or absence of
      TauCl. The culture supernatant was collected and the levels of MMPs were measured
      by enzyme-linked immunosorbent assay (ELISA). The IkappaB signaling pathways
      stimulated by adiponectin were studied and the levels of NF-kappaB in the nuclei
      of the cells were analyzed by ELISA. RESULTS: TauCl (600 microM) inhibited MMP
      13, but not MMP-1, expression in IL-1beta-stimulated RA FLSs. However, TauCl at
      the same concentration significantly inhibited the production of both adiponectin
      stimulated MMP-1 and MMP-13 expression. TauCl inhibited the degradation of
      IkappaB-alpha stimulated by adiponectin, but not by IL-1beta. Similarly, the
      level of NF-kappaB in the nucleus was increased by adiponectin stimulation and
      was inhibited by 600 microM TauCl. However, the levels of NF-kappaB increased by
      IL-1beta stimulation were not inhibited by 600 microM TauCl. CONCLUSIONS: TauCl
      more effectively inhibited MMPs expression induced by adiponectin than that by IL
      1beta in RA FLS, suggesting that TauCl plays an important role in down-regulating
      the expression of MMPs in arthritic joints.

PMID- 20804603
TI  - Stress-responsive gene TauT and acute kidney injury.
AB  - BACKGROUND: Cisplatin is a commonly used chemotherapeutic agent that has a major
      limitation because of its nephrotoxicity. We have demonstrated that cisplatin
      down-regulates the expression of the taurine transporter gene (TauT) in renal
      cells and that forced overexpression of TauT protects against cisplatin-induced
      apoptosis in renal cells in vitro and in vivo. In the present study, we have
      investigated how TauT is regulated by p53 and c-Jun and its role during acute
      kidney injury (AKI). METHODS: Regulation of TauT by p53 and c-Jun was determined
      by reporter gene assay, DNA binding, Western blot analysis, and
      immunohistochemistry. RESULTS: TauT was down-regulated by p53 and up-regulated by
      c-Jun. Two potential binding sites for c-Jun were identified in the promoter
      region of TauT. Inhibition of c-Jun N-terminal kinase (JNK) enhanced TauT
      promoter activity. Overexpression of TauT protects against cisplatin-induced
      kidney injury in a TauT transgenic mouse model. CONCLUSIONS: Our findings suggest
      that TauT plays a critical role in renal function. Expression of TauT is
      negatively regulated by p53 and positively regulated by c-Jun, which is mediated
      by the JNK signaling pathway. The outcome level of TauT may determine the fate of
      renal cells during stress-induced AKI.

PMID- 20804604
TI  - Perinatal taurine exposure alters renal potassium excretion mechanisms in adult
      conscious rats.
AB  - Perinatal taurine exposure has long-term effects on the arterial pressure and
      renal function. This study tests its influence on renal potassium excretion in
      young adult, conscious rats. Female Sprague-Dawley rats were fed normal rat chow
      and given water alone (C), 3% beta-alanine in water (taurine depletion, TD) or 3%
      taurine in water (taurine supplementation, TS), either from conception until
      delivery (fetal period; TDF or TSF) or from delivery until weaning (lactation
      period; TDL or TSL). In Experiment 1, male offspring were fed normal rat chow and
      tap water, while in Experiment 2, beta-alanine and taurine were treated from
      conception until weaning and then female pups were fed normal rat chow and 5%
      glucose in drinking water (CG, TDG or TSG) or water alone (CW, TDW or TSW). At 7
      8 weeks of age, renal potassium excretion was measured at rest and after an acute
      saline load (5% of body weight) in conscious, restrained rats. Although all male
      groups displayed similar renal potassium excretion, TSF rats slightly increased
      fractional potassium excretion at rest but not in response to saline load,
      whereas TDF did the opposite. Plasma potassium concentration was only slightly
      altered by the diet manipulations. In female offspring, none of the perinatal
      treatments significantly altered renal potassium excretion at rest or after
      saline load. High sugar intake slightly decreased potassium excretion at rest in
      TDG and TSG, but only the TDG group displayed a decreased response to saline
      load. The present data indicates that perinatal taurine exposure only mildly
      influences renal potassium excretion in adult male and female rats.

PMID- 20804605
TI  - Taurine bromamine (TauBr)--its role in immunity and new perspectives for clinical
      use.
AB  - This review is an attempt to summarize our knowledge about taurine bromamine
      (TauBr) properties, its role in innate immunity and its therapeutic
      potential.TauBr and taurine chloramine (TauCl) are major haloamines generated by
      eosinophils and neutrophils at a site of inflammation. Both haloamines share anti
      inflammatory and anti-oxidant properties. TauBr, similarly to TauCl, decreases
      the production of proinflammatory mediators. Their anti-inflammatory and anti
      oxidant activities are enhanced by their ability to induce the expression of heme
      oxygenase-1 (HO-1). TauCl is more stable than TauBr. On the other hand, only
      TauBr was found to be highly membrane-permeable showing stronger microbicidal
      activity than TauCl.In the light of the anti-inflammatory and antimicrobial
      properties of TauBr we discuss its therapeutic potential in local treatment of
      inflammation, especially acne vulgaris, the most common inflammatory skin
      disorder. TauBr, at non-cytotoxic concentrations, is able to kill
      Propionibacterium acnes, the skin bacteria involved in pathogenesis of acne
      vulgaris.As topical antibiotics used in the therapy of acne are associated with
      the emergence of resistant bacteria, topical TauBr seems to be a good candidate
      for an alternative therapy.Recently, in a double blind trial, the efficacy of
      TauBr was compared with the efficacy of clindamycin, one of the most common
      topical antibiotics used in acne therapy. Comparable reduction of acne lesions
      was observed in the TauBr and clindamycin groups of patients with mild and
      moderate inflammatory facial acne vulgaris. We conclude that this pilot study
      supports our concept that TauBr can be used as a topical agent in the treatment
      of acne vulgaris, especially in patients who have already developed antibiotic
      resistance. Further studies are necessary to substantiate the more extended use
      of TauBr as an anti-inflammatory and anti-oxidant agent in human medicine.

PMID- 20804606
TI  - High sugar intake via the renin-angiotensin system blunts the baroreceptor reflex
      in adult rats that were perinatally depleted of taurine.
AB  - Perinatal taurine depletion leads to several physiological impairments in adult
      life, in part, due to taurine's effects on the renin-angiotensin system, a
      crucial regulator of growth and differentiation during early life. The present
      study tests the hypothesis that perinatal taurine depletion predisposes adult
      female rats to impaired baroreceptor control of arterial pressure by altering the
      renin-angiotensin system. Female Sprague Dawley (SD) rats were fed normal rat
      chow and from conception to weaning drank 3% beta-alanine in water (taurine
      depletion, TD) or water alone (Control, C). Female offspring ate a normal rat
      chow and drank water with (G) or without (W) 5% glucose throughout the
      experiment. To test the possible role of the renin-angiotensin system, 50% of the
      rats received captopril (an angiotensin converting enzyme inhibitor, 400 mg/L)
      from 7 days before parameter measurements until the end of experiment. At 7-8
      weeks of age, arterial pressure, heart rate, baroreflex control of heart rate and
      renal nerve activity were studied in either conscious, freely moving or
      anesthetized rats. Perinatal taurine depletion did not alter resting mean
      arterial pressure or heart rate in the adult female offspring that received
      either high or normal sugar intake. Captopril treatment slightly decreased mean
      arterial pressure but not heart rate in all groups. Compared to controls, only
      the TDG rats displayed blunted baroreflex responses. Captopril treatment
      normalized baroreflex sensitivity in TDG. The present data indicate that in
      perinatal taurine depleted female rats, the renin-angiotensin system underlines
      the ability of high sugar intake to blunt baroreceptor responses.

PMID- 20804607
TI  - Adult renal function is modified by perinatal taurine status in conscious male
      rats.
AB  - Perinatal taurine exposure influences renal function in adult female offspring.
      This study tests the hypothesis that prenatal rather than postnatal taurine
      exposure alters renal function in adult conscious male rats. Female Sprague
      Dawley rats were fed normal rat chow and tap water alone (Control), tap water
      containing 3% beta-alanine (taurine depletion, TD) or tap water containing 3%
      taurine (taurine supplementation, TS) either from conception until delivery
      (fetal period; TDF or TSF) or from delivery until weaning (lactation period; TDL
      or TSL). After weaning, male offspring were fed with the normal rat chow and tap
      water ad libitum. At 7-8 weeks of age, renal function was studied in conscious,
      restrained rats. Mean arterial pressures were slightly higher in rats receiving
      taurine supplementation during either the fetal or lactation periods (compared to
      Control and TD groups), but heart rates were not significantly different among
      groups. Effective renal blood flows were lower in TDF, TDL, and TSF rats (TDF
      4.6+/-0.8 ml/min/g kidney weight (KW), TDL 3.0+/-0.9 ml/min/g KW, and TSF 2.8+/
      0.7 ml/min/g KW) than in TSL (7.7+/-0.9 ml/min/g KW) or Control rats (7.3+/-1.6
      ml/min/g KW). These differences were correlated with significant increases in
      renal vascular resistance in TDF, TDL, and TSF groups compared to TSL and Control
      rats. In contrast, glomerular filtration rates were not significantly different
      among groups. Although basal water and sodium excretion were slightly lower in
      TDL and TSF rats compared to other groups, their diuretic and natriuretic
      responses to an acute saline load were not different from Control. The present
      data indicate that in adult male rats, both perinatal supplementation and
      depletion of taurine can alter renal hemodynamics, and these effects are
      differentially time-dependent.

PMID- 20804608
TI  - Differential effects of taurine treatment and taurine deficiency on the outcome
      of renal ischemia reperfusion injury.
AB  - Taurine possesses membrane stabilization, osmoregulatory and antioxidant
      properties, aspects of relevance to ischemic injury. We tested the hypothesis
      that body taurine status is a determinant of renal ischemic injury. Accordingly,
      renal function and structure were examined in control (C), taurine-treated (TT)
      and taurine deficient (TD) rats that were subjected to bilateral renal ischemia
      (60 min) followed by reperfusion (IR); sham operated rats served as controls.
      Baseline urine osmolality was greater in the TD group than in the control and the
      TT groups, an effect associated with increased renal aquaporin 2 level. The IR
      insult reduced urine osmolality (i.e., day-1 post insult); the TD/IR group
      displayed a more marked recovery in urine osmolality by day-6 post insult than
      the other two groups. Fluid and sodium excretions were lower in the TD/IR group,
      suggesting propensity to retention. Histopathological examination revealed the
      presence of tubular necrotic foci in the C/IR group than sham controls. While
      renal architecture of the TD/IR group showed features resembling sham controls,
      the TT/IR group showed dilated tubules, which lacked immunostaining for aquaporin
      2, but not 1, suggestive of proximal tubule origin. Finally, assessment of cell
      proliferation and apoptosis revealed lower proliferation but higher apoptotic
      foci in the TT/IR group than other IR groups. Collectively, the results indicate
      that body taurine status is a major determinant of renal IR injury.

PMID- 20804609
TI  - Characterization of taurine as anti-obesity agent in C. elegans.
AB  - BACKGROUND: Taurine plays an important role in reducing physiological stress.
      Recent studies indicated that taurine may serve as an anti-obesity agent at the
      cellular level. This study characterizes taurine's potential anti-obesity
      function in C. elegans, which have become a popular in vivo model for
      understanding the regulatory basis of lipid biosynthesis and deposition. METHODS:
      Two strains of C. elegans were raised on a normal or high-fat diet: N2 (normal)
      and RB1600, a mutant in tub-1 that serves as a tubby homologue and functions
      parallel to the 3-ketoacyl-CoA thiolase gene (kat-1) in regulating lipid
      accumulation. Taurine's effect on lipid deposition was characterized according to
      assays of Sudan black B staining, triglyceride content measurement, food
      consumption, and mobility comparison. RESULTS: When N2 was treated with taurine
      after the culture in the high-fat media, the worms showed lower lipid
      accumulation in the assays of the Sudan black B staining and the triglyceride
      quantification. The anti-obesity effect was less evident in the experiment for
      RB1600. When the amount of taurine was increased for the high-fat-diet-treated N2
      strain, fat deposition decreased and mobility increased in a dose-dependent
      manner. In the food consumption assays, taurine did not cause a significant
      change in food intake. CONCLUSIONS: Taken together, these results strongly imply
      that taurine plays an important role in reducing fat deposition by modulating
      cellular pathways for lipid accumulation and stimulating mobility, but not the
      pathways for lipid biosynthesis and food intake.

PMID- 20804610
TI  - Deterioration of traditional dietary custom increases the risk of lifestyle
      related diseases in young male Africans.
AB  - BACKGROUND: Prevalence of metabolic syndrome (MS) is rapidly increasing
      worldwide. To investigate the spread of MS risks and its relationship with eating
      habits including fish intake, we carried out a health examination for young and
      middle-aged men. METHODS: The subjects were 97 healthy men (20 to 50 years)
      living in Mwanza, located on the shore of Lake Victoria in Tanzania. The health
      examination was conducted according to the basic protocol of WHO-CARDIAC
      (Cardiovascular Diseases and Alimentary Comparison) Study. This survey included
      anthropometric measurements, a dietary questionnaire, blood pressure measurement,
      and blood and 24-hour urine (24U) collection. Excretions of sodium, potassium and
      taurine (Tau) in 24U were estimated as the biomarkers of salt, vegetable and fish
      product intakes respectively. RESULTS: In this survey, 62.5 % of the young and
      63.3% of the middle-aged adults had MS risks. The most prevalent MS risk factor
      was increased blood pressure (50.0% of young adults and 53.1% of the middle
      aged). Tau excretions in 24U and n-3 fatty acid levels in plasma were
      significantly lower in young adults than those in the middle-aged (both P <
      0.05). The eating frequencies of non-traditional foods such as donuts and ice
      cream showed negative correlations with age (r = -0.282, P < 0.01 and r = -0.246,
      P < 0.05), while salt intake positively correlated with age (r = 0.236, P <
      0.05). Tau excretion in 24U was inversely correlated with atherosclerosis index
      (r = -0.306, P < 0.01) and fasting blood glucose (r = -0.284, P < 0.05).
      CONCLUSIONS: Young adults in Mwanza had a decreased frequency of eating habit of
      fish products compared with the middle-aged as indicated by Tau excretion in 24U
      and n-3 fatty acid level in the plasma, and over half of young adults had one or
      more MS risks just as the middle-aged. The change in food habit of lowered fish
      intake and raised exotic food intake might be concluded to increase MS risks in
      young men.

PMID- 20804611
TI  - Comparison of the protective actions of N-acetylcysteine, hypotaurine and taurine
      against acetaminophen-induced hepatotoxicity in the rat.
AB  - When used in overdoses, acetaminophen (APAP) is a common cause of morbidity and
      mortality in humans. At present, N-acetylcysteine (NAC) is the antidote of choice
      for acetaminophen overdoses. Prompt administration of NAC can prevent the
      deleterious actions of APAP in the liver. In view of the similarities in
      antioxidant effects demonstrated by NAC, hypotaurine (HYTAU) and taurine (TAU) in
      this and other our laboratories, the present study was undertaken to compare
      these compounds for the ability to attenuate plasma and liver biochemical changes
      associated with a toxic dose of APAP. For this purpose, fasted male Sprague
      Dawley rats, 225-250 g in weight, were intraperitoneally treated with APAP (800
      mg/kg), NAC, HYTAU or TAU (2.4 mM/kg) followed 30 min later by APAP, or 50% PEG
      400 (the vehicle for APAP). At 6 hr after APAP administration, all animals were
      sacrificed by decapitation and their blood and livers collected. The plasma
      fractions were analyzed for indices of liver damage (alanine transaminase,
      aspartate transaminase, lactate dehydrogenase), levels of malondialdehyde (MDA),
      reduced (GSH) and oxidized (GSSG) glutathione, and activities of glutathione
      reductase (GR), glutathione S-transferase (GST) and gamma-glutamylcisteinyl
      synthetase (GCS). Suitable liver homogenates were analyzed for the same
      biochemical parameters as the plasma but indices of liver damage. By itself, APAP
      increased MDA formation and had a significant lowering influence on the levels of
      GSH and GSSG, the GSH/GSSH ratio, and the activities of GR, GST and GCS both in
      the plasma and liver. In addition, APAP promoted the leakage of transaminases and
      lactate dehydrogenase from the liver into the plasma. Without exceptions, a
      pretreatment with a sulfur-containing compound led to a significant attenuation
      of the liver injury and the biochemical changes induced by APAP. Within a narrow
      range of potency differences, HYTAU appeared to be the most protective and TAU
      the least. The present results suggest that, irrespective of the differences in
      structural features and in vitro antioxidant properties that may exist among NAC,
      TAU and HYTAU, these compounds demonstrate equivalent patterns of protection and,
      to a certain extent, equipotent protective actions against the toxic actions of
      APAP in the liver when tested in equimolar doses and under the same conditions in
      an animal model.

PMID- 20804612
TI  - Metabolic bone disease in lion cubs at the London Zoo in 1889: the original
      animal model of rickets.
AB  - In 1889 Dr. John Bland-Sutton, a prominent London surgeon, was consulted about
      fatal rickets in over 20 successive litters of lion cubs born at the London Zoo.
      He evaluated the diet and found the cause of rickets to be nutritional in origin.
      He recommended that goat meat with crushed bones and cod-liver oil be added to
      the lean horsemeat diet of the cubs and their mothers. Rickets were reversed, the
      cubs survived, and subsequent litters thrived. Thirty years later, in classic
      controlled studies conducted in puppies and young rats, the definitive role of
      calcium, phosphate and vitamin D in prevention and therapy of rickets was
      elucidated. Further studies led to identifying the structural features of vitamin
      D.Although the Bland-Sutton diet provided calcium and phosphate from bones and
      vitamins A and D from cod-liver oil, some other benefits of this diet were not
      recognized. Taurine-conjugated bile salts, necessary for intestinal absorption of
      fat-soluble vitamins, were provided in the oil cold-pressed from cod liver.
      Unlike canine and rodent species, felines are unable to synthesize taurine, yet
      conjugate bile acids exclusively with taurine; hence, it must be provided in the
      diet. The now famous Bland-Sutton "experiment of nature," fatal rickets in lion
      cubs, was cured by addition of minerals and vitamin D. Taurine-conjugated bile
      salts undoubtedly permitted absorption of vitamins A and D, thus preventing the
      occurrence of metabolic bone disease and rickets.

PMID- 20804613
TI  - Regulation of taurine transport at the blood-placental barrier by calcium ion,
      PKC activator and oxidative stress conditions.
AB  - BACKGROUND: In the present study, we investigated the changes of uptake and
      efflux transport of taurine under various stress conditions using rat
      conditionally immortalized syncytiotrophoblast cell line (TR-TBT cells), as in
      vitro blood-placental barrier (BPB) model. METHODS: The transport of taurine in
      TR-TBT cells were characterized by cellular uptake study using radiolabeled
      taurine. The efflux of taurine was measured from the amount of radiolabeled
      taurine remaining in the cells after the uptake of radiolabeled taurine for 60
      min. RESULTS: Taurine uptake was significantly decreased by phosphorylation of
      protein kinase C (PKC) activator in TR-TBT cells. Also, calcium ion (Ca2+) was
      involved in taurine transport in TR-TBT cells. Taurine uptake was inhibited and
      efflux was enhanced under calcium free conditions in the cells. In addition,
      oxidative stress induced the change of taurine transport in TR-TBT cells, but the
      changes were different depending on the types of oxidative stress inducing
      agents. Tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS) and
      diethyl maleate (DEM) significantly increased taurine uptake, but H2O2 and nitric
      oxide (NO) donor decreased taurine uptake in the cells. Taurine efflux was down
      regulated by TNF-alpha in TR-TBT cells. CONCLUSION: Taurine transport in TR-TBT
      cells were regulated diversely at extracellular Ca2+ level, PKC activator and
      oxidative stress conditions. It suggested that variable stresses affected the
      taurine supplies from maternal blood to fetus and taurine level of fetus.

PMID- 20804614
TI  - A maternal low protein diet has pronounced effects on mitochondrial gene
      expression in offspring liver and skeletal muscle; protective effect of taurine.
AB  - BACKGROUND: Low birth weight is associated with an increased risk of developing
      impaired glucose tolerance, and eventually type 2 diabetes in adult life.
      Gestational protein restriction in rodents gives rise to a low birth weight
      phenotype in the offspring. RESULTS: We examined gene expression changes in liver
      and skeletal muscle of mice subjected to gestational protein restriction (LP) or
      not (NP), with or without taurine supplementation in the drinking water. LP
      offspring had a 40% lower birth weight than NP offspring, with taurine preventing
      half the decrease. Microarray gene expression analysis of newborn mice revealed
      significant changes in 2012 genes in liver and 967 genes in skeletal muscle of LP
      offspring. Taurine prevented 30% and 46% of these expression changes,
      respectively. Mitochondrial genes, especially those involved with oxidative
      phosphorylation, were more abundantly changed than other genes. The mitochondrial
      genes were mainly upregulated in liver, but downregulated in skeletal muscle,
      despite no change in citrate synthase activity in either tissue. Taurine
      preferentially rescued genes concerned with fatty acid metabolism in liver and
      with oxidative phosphorylation and TCA cycle in skeletal muscle. A mitochondrial
      signature was seen in the liver of NP offspring with taurine supplementation, as
      gene sets for mitochondrial ribosome as well as lipid metabolism were over
      represented in 4-week-old offspring subjected to gestational taurine
      supplementation. Likewise, 11 mitochondrial genes were significantly upregulated
      by gestational taurine supplementation in 4-week-old NP offspring. CONCLUSIONS:
      Gestational protein restriction resulted in lower birth weight associated with
      significant gene expression changes, which was different in liver and muscle of
      offspring. However, a major part of the birth weight decrease and the expression
      changes were prevented by maternal taurine supplementation, implying taurine is a
      key factor in determining expression patterns during development and in that
      respect also an important component in metabolic fetal programming.

PMID- 20804615
TI  - Antioxidant and hepatic protective effects of lotus root hot water extract with
      taurine supplementation in rats fed a high fat diet.
AB  - BACKGROUND: Nelumbo nucifera, known as sacred lotus, is a well-known medicinal
      plant and this lotus root is commonly used as food compared to different parts of
      this plant. This study was conducted to investigate the antioxidant and hepatic
      protective effects of lotus root hot water extract with taurine supplementation
      in high fat diet-induced obese rats. METHODS: Thirty-two male Sprague-Dawley rats
      (4-week-old) were randomly divided into four groups (n=8) for 6 weeks (normal
      diet, N group; high fat diet, HF group; high fat diet + lotus root hot water
      extract, HFR group; high fat diet + lotus root hot water extract + taurine, HFRT
      group). Lotus root hot water extract was orally administrated (400 mg/kg/day) to
      HFR and HFRT groups and the same amount of distilled water was orally
      administered to N and HF groups. Taurine was supplemented by dissolving in feed
      water (3% w/v). RESULTS: The activities of glutamate oxaloacetate transaminase
      and glutamate pyruvate transaminase in serum were lower in HFR and HFRT groups
      compared to HF group. Thiobarbituric acid reactive substance contents in all
      groups fed a high fat diet were higher compared to N group. The activities of
      hepatic antioxidant enzymes were higher in HFR and HFRT groups compared to HF
      group. CONCLUSIONS: These results suggest that lotus root hot water extract with
      taurine supplementation shows antioxidant and hepatic protective effects in high
      fat diet-induced obese rats.

PMID- 20804617
TI  - Dietary taurine intake, nutrients intake, dietary habits and life stress by
      depression in Korean female college students: a case-control study.
AB  - BACKGROUND: The purpose of this study was to investigate the dietary taurine
      intake, nutrients intake, dietary habits and life stress by depression in Korean
      female college students. METHODS: In this study, research data were collected in
      March 2009 and 65 patients with depression and 65 controls without depression
      participated. The CES-D (Center for Epidemiologic Studies Depression) scale was
      used for depression measure and controls were matched for age. A 3-day recall
      method was used for dietary assessment (2 weekdays and 1 weekend day). RESULTS:
      Average height, weight and body mass index (BMI) were 161.3+/-0.5 cm, 55.3+/-1.0
      kg and 21.2+/-0.4 kg/m2 for depression patients and those of control group were
      161.4+/-0.7 cm, 53.1+/-0.8 kg and 20.3+/-0.2 kg/m2, respectively. Average dietary
      taurine intakes of depression patients and control group were 89.1 and 88.0
      mg/day, respectively. There was no significant difference in dietary taurine
      intake between depression patients and control group. The average intakes of
      vitamin A (p<0.05), beta-carotene (p<0.01), vitamin C (p<0.05), folic acid
      (p<0.05) and fiber (p<0.05) of depression patients were significantly lower
      compared to control group. The average total dietary habit score of depression
      patients (47.2) was significantly lower than that of control group (51.3)
      (p<0.01). The average dietary habit scores of "eating meals at regular times"
      (p<0.05), "eating adequate amount of meals" (p<0.05), "having meals with diverse
      foods" (p<0.05), "avoiding eating spicy foods" (p<0.01) and "eating protein foods
      such as meat, fish, eggs, beans more than 2 times a day" (p<0.05) were
      significantly lower in depression patients compare to control group. The average
      scores of total life stress (p<0.001) and all stress categories of depression
      patients were significantly higher than those of control group except faculty
      problem score. CONCLUSIONS: These results show that depression patients have poor
      dietary habits and unbalanced nutrition status. Also depression patients have
      higher life stress score.Therefore, continuous nutrition education and
      counselling for good dietary habits and balanced nutrition status are needed to
      prevent depression in Korean college students.

PMID- 20804616
TI  - Taurine and the renal system.
AB  - Taurine participates in a number of different physiologic and biologic processes
      in the kidney, often reflected by urinary excretion patterns. The kidney is key
      to aspects of taurine body pool size and homeostasis. This review will examine
      the renal-taurine interactions relative to ion reabsorption; renal blood flow and
      renal vascular endothelial function; antioxidant properties, especially in the
      glomerulus; and the role of taurine in ischemia and reperfusion injury. In
      addition, taurine plays a role in the renal cell cycle and apoptosis, and
      functions as an osmolyte during the stress response. The role of the kidney in
      adaptation to variations in dietary taurine intake and the regulation of taurine
      body pool size are described. Finally, the protective function of taurine against
      several kidney diseases is reviewed.

PMID- 20804618
TI  - A case-control study on the dietary taurine intake, nutrient status and life
      stress of functional constipation patients in Korean male college students.
AB  - BACKGROUND: Constipation is a common gastrointestinal symptom in Korea as well as
      in Western countries. This study was performed to investigate the dietary taurine
      intake, nutrient status, and life stress of functional constipation (FC) patients
      in Korean male college students. METHODS: Research data were collected in 2008
      and a total of 104 male students (52 with FC patients and 52 healthy controls
      without FC) were included. FC patients were defined by the codes for the Rome
      Modular Questionnaire and healthy controls without FC were matched for age,
      height, weight and BMI. A self-administered life stress score and 3-day recall
      method were used to assess life stress level and dietary intake, respectively.
      RESULTS: The averages of age, height, weight, body fat percentage and body mass
      index (BMI) of male students were 23.4 years, 174.1 cm, 71.9 kg, 19.0 % and 23.7
      kg/m2, respectively. Average intake of dietary taurine was 126.8 mg/day in FC
      patients and 105.1 mg/day in control group. The average intake of total calorie
      (p<0.05), plant protein (p<0.01), plant fat (p<0.001), carbohydrate (p<0.05),
      plant calcium (p<0.05) of FC patients were significantly higher compared to
      control group. The average total life stress score (p<0.01), economy problem
      score (p<0.05), future problem score (p<0.05) and value problem score (p<0.05) of
      FC patients were significantly higher compared to control group. CONCLUSIONS:
      These results may suggest that FC patients show a higher life stress score and
      intake of some nutrient such as total calorie, plant protein, plant fat,
      carbohydrate and plant calcium in Korean male college students. Therefore, a
      further large-scale study is needed about correlation between life stress and
      nutrients intake including dietary taurine.

PMID- 20804619
TI  - Antiobesity and hypolipidemic effects of lotus leaf hot water extract with
      taurine supplementation in rats fed a high fat diet.
AB  - BACKGROUND: Lotus (Nelumbo nucifera) leaf has been used to treat obesity. The
      purpose of this study was to investigate the antiobesity and hypolipidemic
      effects of lotus leaf hot water extract with taurine supplementation in high fat
      diet-induced obese rats. METHODS: Four week-old male Sprague-Dawley rats were
      randomly divided into four groups with 8 rats in each group for a period of 6
      weeks (normal diet, N group; high fat diet, HF group; high fat diet + lotus leaf
      hot water extract, HFL group; high fat diet + lotus leaf hot water extract +
      taurine, HFLT group). Lotus leaf hot water extract was orally administrated to
      HFL and HFLT groups and the same amount of distilled water was orally
      administered (400 mg/kg/day) to N and HF groups. Taurine was supplemented by
      dissolving in feed water (3% w/v). RESULTS: The body weight gain and relative
      weights of epididymal and retroperitoneal adipose tissues were significantly
      lower in N, HFL and HFLT groups compared to HF group. HFL and HFLT groups showed
      lower concentrations of total cholesterol, triglyceride and low density
      lipoprotein cholesterol in serum. HFLT group showed higher the ratio of high
      density lipoprotein cholesterol/total cholesterol compared to HFL group. HFLT
      group showed better blood lipid profiles compared to HFL group. CONCLUSIONS:
      Lotus leaf hot water extract with taurine supplementation showed antiobesity and
      hypolipidemic effects in high fat diet-induced obese rats, which was more
      effective than lotus leaf hot water extract alone.

PMID- 20804620
TI  - Taurine in morning spot urine for the useful assessment of dietary seafood intake
      in Japanese children and adolescents.
AB  - BACKGROUND: Since our previous report on WHO CARDIAC Study data demonstrated that
      24-hour urinary (24U) taurine (Tau) excretion was a useful biomarker of seafood
      (SF) intake and inversely related to the mortality rates of stroke and coronary
      heart diseases in the world, we determined that SF is important in the risk
      reduction of lifestyle related-diseases. The amounts of dietary SF intake are so
      far estimated from a nutritional survey or 24U Tau excretion.The sodium/potassium
      ratio of spot urine (SU) and the 24U ratio were reported to be significantly
      correlated with. Therefore, we presently examined the relationship of Tau
      excretion in the morning SU with 24U Tau for simplifying the population
      comparison and the follow-up of SF intake changes in the process of food
      education program (FEP). METHODS: After informed consent was obtained, 54
      children aged 6-11 years (Children) and 193 adolescents aged 13-18 years
      (Adolescents) participated in collecting precisely 24U and SU of the first
      urination on the same day and answered the questionnaire including age and height
      and weight measurements. The urine samples were measured for creatinine (Cre) and
      Tau, and the association of these between 24U and SU were analyzed. RESULTS: The
      success rates of 24U sampling were very high in Children and Adolescents, 96.4%
      and 82.4%, respectively. From the result of the multiple regression analysis of
      SU Tau/Cre and weight we obtained formulas for predicting 24U Tau excretion in
      Children and Adolescents as follows: Children: 24U Tau = 16.3 (weight) + 314.3
      (SU Tau/Cre) -175.2; and Adolescents: 24U Tau = 20.2 (weight) + 644.7 (SU
      Tau/Cre) - 569.4. CONCLUSIONS: The present study established the regression
      equation to estimate 24U Tau excretion from SU Tau/Cre and weight. These formulas
      are expected to contribute to the estimation of fish and SF intake and the follow
      up of the change of the dietary behavior by FEP in Children and Adolescents.

PMID- 20804621
TI  - Quality and safety issues related to traditional animal medicine: role of
      taurine.
AB  - BACKGROUND: Calculus Bovis (:C.Bovis) is one of the most precious and commonly
      used medicinal materials in Japan and China. As the natural occurrence is very
      rare, a source of supply for C. Bovis is far behind the actual need and great
      efforts have been taken for some substitutes of natural C. Bovis. Unfortunately,
      very little information is available on the quality and/or clinical efficacy of
      medication based on C. Bovis. To ensure sustainable use of traditional
      therapeutic agents derived from C. Bovis, we felt that several issues needed to
      be addressed: 1) the source of the C. Bovis materials and quality control; 2) the
      role of taurine in the efficacy of C. Bovis. METHODS: Nine samples of natural C.
      Bovis and its substitutes were collected. ICP-MS was used for elemental analysis
      and the characterization was performed by principal component analysis (PCA) and
      soft independent modeling of class analogy (SIMCA) as multivariate approaches.
      The efficacy of C. Bovis was evaluated for morphology, viability and beating
      pattern on cultured cardiac myocytes and/or fibroblasts. RESULTS: PCA and multi
      elemental focus was effective in discriminating C. Bovis samples derived from
      different habitats. A satisfactory classification using SIMCA was obtained among
      Australia C. Bovis, other habitats and the substitutes. Australian samples had
      better batch uniformity than other habitats and were composed of fewer elements.
      We have used Australian C. Bovis for assessment on its bioactive compounds. Rat
      cardiac cells incubated with C. Bovis extract (0.01-0.1 mg/ml) maintained normal
      morphology, viability and beating pattern. Cardiac myocytes and fibroblasts
      treated for 48 h with CA (0.5 mM) or DCA (0.1 mM) caused cell injury, as
      reflected by changes in appearance and a reduction of viability detected by the
      MTS assay. In cardiomyocytes, 0.5 h exposure of CA (0.5 mM) markedly decreased
      the velocity ratio of beating, whereas the simultaneous addition of 1 mM taurine
      largely prevented the decrease. CONCLUSIONS: The multi-elemental focus provided
      some references for the quality control and the efficacy of C. Bovis. Taurine
      partly attenuated the harmful actions of bile acids. It is plausible that the
      relationship between taurine and the bile acids contributes to therapeutic effect
      of C. Bovis.

PMID- 20804622
TI  - Effect of combination of taurine and azelaic acid on antimelanogenesis in murine
      melanoma cells.
AB  - BACKGROUND: Pigmentation in human skin is an important defense mechanism against
      sunlight or oxidative stress. Despite the protective role of melanin, abnormal
      hyperpigmentation such as freckles and chloasma sometimes can be serious
      aesthetic problems. Because of these effects of hyperpigmentation, people have
      considered the effect of depigmentation. Azelaic acid (AZ) is a saturated
      dicarboxylic acid found naturally in wheat, rye, and barley. Previously, we
      showed that AZ inhibited melanogenesis. In this study, we investigated the
      antimelanogenic activity of combination of AZ and taurine (Tau) in B16F10 mouse
      melanoma cells. METHODS: The mouse melanoma cell line B16F10 was used in the
      study. We measured melanin contents and tyrosinase activity. To gain the change
      of protein expression, we carried out western blotting. RESULTS: We investigated
      that AZ combined with taurine (Tau) show more inhibitory effects in melanocytes
      than the treatment of AZ alone. AZ combined with Tau inhibited the melanin
      production and tyrosinase activity of B16F10 melanoma cells without significant
      cytotoxicity. Also inhibitory effects after treatment with these combined
      chemical are stronger than AZ alone on melanogenesis. CONCLUSIONS: These findings
      indicate that AZ with Tau might play an important role in the regulation of
      melanin formation and be useful as effective ingredients in antimelanogesis.

PMID- 20804623
TI  - Preventive effect of taurine on experimental type II diabetic nephropathy.
AB  - BACKGROUND: It has been verified that taurine has some preventive effects on
      diabetes and its complications when used alone or together with other drugs, but
      there are few reports about taurine on the prevention of diabetic nephropathy,
      the mechanisms of which are still unknown. METHODS: Taurine was administered to
      type diabetic rats induced by high fat high sugar diet combined with STZ
      injection. The preventive effect of taurine on diabetic nephropathy was
      investigated by detecting blood glucose, lipid metabolism, kidney function and
      glomerular basement membrane metabolism. RESULTS: Taurine could lower blood
      glucose, TG, TC, BUN, Scr, NAG, U-PRO, the expression of laminin B1(LBN1) mRNA,
      and increase HDL-C of diabetic rats. CONCLUSIONS: The results indicated that
      taurine could prevent the occurrence and development of diabetic nephropathy by
      decreasing blood glucose, improving lipid metabolism, glomerular basement
      membrane metabolism, and kidney function.

PMID- 20804624
TI  - Taurine's health influence on Japanese high school girls.
AB  - BACKGROUND: The prevalence of metabolic syndrome (MS) in children and adolescents
      has been increasing at an alarming rate. MS risks during childhood and
      adolescence adversely affect health conditions in later life. Thus, the
      characterization of their MS risks is a critical research field. The aims of this
      study are to survey the health status of Japanese adolescent females, a poorly
      characterized population, and to investigate the potential relationship between
      their MS risks and dietary factors like potassium (K) and taurine. METHODS:
      Anthropometric characteristics of 243 healthy school girls aged 13 to 18 years
      were measured. Serum levels of triglycerides, total cholesterol and high-density
      lipoprotein (HDL), and plasma levels of glucose and insulin were analyzed in
      fasting blood samples. We assessed overweight, disturbed lipid prolife, higher
      blood pressure (hBP) and higher plasma glucose (hGlc) levels as indicators of MS
      risks. The relationships between MS risks and urinary K or taurine excretion were
      investigated by dividing into higher and lower groups at medians of their urinary
      excretions. RESULTS: Half of junior high school (JHS) and one-quarter of senior
      high school (SHS) girls had at least one MS risk. The quite common risk was hGlc,
      the rates being 21% in JHS girls and 14% in SHS. The prevalence of being
      overweight and obesity were only small portions, the rate being 0% and 0% in JHS
      girls, and 10% and 1% in SHS, respectively. Substantial differences in the
      prevalence of hBP were observed between JHS (22%) and SHS (4%) girls.
      Furthermore, higher urinary K excretion group showed a significant decrease in
      triglyceride level (P = 0.03) and increase in HDL level (P = 0.003) compared with
      the lower. Also, the higher urinary taurine excretion group exhibited a
      significant reduction in triglyceride level (P = 0.04) compared with the lower.
      CONCLUSIONS: These results indicate that control of plasma glucose level rather
      than body weight is a crucial task in Japanese pubertal girls, and that a dietary
      habit rich in K and taurine could improve their lipid profile. Nutritional
      education based on these findings would help to prevent the future development of
      MS in Japanese female adolescents.

PMID- 20804625
TI  - Reciprocal regulation between taurine and glutamate response via Ca2+-dependent
      pathways in retinal third-order neurons.
AB  - Although taurine and glutamate are the most abundant amino acids conducting
      neural signals in the central nervous system, the communication between these two
      neurotransmitters is largely unknown. This study explores the interaction of
      taurine and glutamate in the retinal third-order neurons. Using specific
      antibodies, both taurine and taurine transporters were localized in
      photoreceptors and Off-bipolar cells, glutamatergic neurons in retinas. It is
      possible that Off-bipolar cells release juxtaposed glutamate and taurine to
      activate the third-order neurons in retina. The interaction of taurine and
      glutamate was studied in acutely dissociated third-order neurons in whole-cell
      patch-clamp recording and Ca2+ imaging. We find that taurine effectively reduces
      glutamate-induced Ca2+ influx via ionotropic glutamate receptors and voltage
      dependent Ca2+ channels in the neurons, and the effect of taurine was selectively
      inhibited by strychnine and picrotoxin, but not GABA receptor antagonists,
      although GABA receptors are present in the neurons. A CaMKII inhibitor partially
      reversed the effect of taurine, suggesting that a Ca2+/calmodulin-dependent
      pathway is involved in taurine regulation. On the other hand, a rapid influx of
      Ca2+ through ionotropic glutamate receptors could inhibit the amplitude and
      kinetics of taurine-elicited currents in the third-order neurons, which could be
      controlled with intracellular application of BAPTA a fast Ca2+ chelator. This
      study indicates that taurine is a potential neuromodulator in glutamate
      transmission. The reciprocal inhibition between taurine and glutamate in the
      postsynaptic neurons contributes to computation of visual signals in the retinal
      neurons.

PMID- 20804626
TI  - Taurine in health and diseases: consistent evidence from experimental and
      epidemiological studies.
AB  - Taurine (T) was first noted as beneficial for stroke and cardiovascular diseases
      (CVD) prevention in genetic rat models, stroke-prone spontaneously hypertensive
      rats (SHRSP). The preventive mechanisms of T were ascribed to sympathetic
      modulation for reducing blood pressure (BP) and anti-inflammatory action. Recent
      epidemiological surveys revealed the involvement of inflammatory mediators in the
      pathogenesis of stroke and also atherosclerosis for which T was proven to be
      effective experimentally. Arterio-lipidosis prone rats, a substrain of SHRSP
      selectively bred for higher reactive hypercholesterolemia, quickly develop not
      only arterial fat deposition but also fatty liver which could be attenuated by
      dietary T supplementation. CARDIAC (CVD and Alimentary Comparison) Study was a
      WHO-coordinated multi-center epidemiological survey on diets and CVD risks and
      mortalities in 61 populations. Twenty-four-hour urinary (24U) T was inversely
      related significantly with coronary heart disease mortality. Higher 24U-T
      excreters had significantly lower body mass index, systolic and diastolic BP,
      total cholesterol (T-Cho), and atherogenic index (AI: T-Cho/high density
      lipoprotein-cholesterol) than lower T excreters. T effects on CVD risks were
      intensified in individuals whose 24U-T and -magnesium (M) excretions were higher.
      Furthermore, higher Na excreters with higher heart rate whose BP were
      significantly higher than those with lower heart rate were divided into two
      groups by the mean of 24U-T, high and low T excreters. Since the former showed
      significantly lower BP than the latter, T may beneficially affect salt-sensitive
      BP rise. Included among the typical 61 populations, were Guiyang, China or St.
      John's, Newfoundland, Canada where in which the means of both 24U-T and -M were
      high or low, respectively. The former and the latter had low and high CVD risks,
      respectively. Australian Aboriginals living at the coastal area in Victoria were
      supposed to eat T- and M-rich bush and sea foods and be free from CVD 200 years
      ago, but they presently have nearly the highest CVD risks indicating that T-
      and/or M-containing seafood, vegetables, fruits, nuts, milk, etc, similar to
      prehistoric hunters' and gatherers' food should be good for CVD prevention. The
      preventive effects of T, good for health and longevity, first noted
      experimentally, were also proven epidemiologically in humans.

PMID- 20804627
TI  - Protection effect of taurine on nitrosative stress in the mice brain with chronic
      exposure to arsenic.
AB  - BACKGROUND: Arsenic exposure induces overproduction of reactive nitrogen species
      (RNS) in brain tissue and results in nucleic acid damage to the nerve cells. The
      8-nitroguanine is one of the major products formed by the reaction of guanine,
      and ONOO-, and has been used as a popular biomarker of nucleic acid damage due to
      RNS attacking. In the present study, we examined whether the administration of
      taurine can protect against nucleic acid damage of brain neurons by arsenic
      induced RNS. MATERIALS AND METHODS: Sixty mice (30 male and 30 female) weighing
      19.5 +/- 1.5 g were divided into 3 groups: (1) control group, (2) experimental
      group that received arsenic (As2O3), and (3) antagonistic group that received
      taurine with arsenic. Arsenic was administered for 60 days. 8-Nitroguanine
      expressions in brain neurons of mice were examined by the immunohistochemical
      method. Histopathological changes in brain tissues of mice were observed under
      light microscope and the immunohistochemistry method was used to investigate 8
      nitroguanine expressions in cerebrum and cerebellum of mice. RESULTS: In the
      control group, no abnormal histopathological changes were observed in brain
      tissue of the mice. In brain tissue of the mice exposed to arsenic,
      histopathological results showed swells, evident vacuolar degeneration in
      cytoplasm, karyorrhexis and karyolysis. Relatively light pathological changes
      were observed in brain of the mice co-administered arsenic and taurine. Little or
      no expression of 8-nitroguanine in brain tissue was observed in controls.
      However, intensive expression of 8-nitroguanine was found in brain tissue of mice
      exposed to arsenic and it was mainly distributed in nucleus neighbouring the
      nuclear membrane, but a little in cytoplasm. A weak expression of 8-nitroguanine
      was observed in brain cells of mice co-administered arsenic and taurine.
      CONCLUSIONS: The brain neurons may be the major target cells of arsenic
      neurotoxicity. Co-administration of arsenic and taurine can alleviate DNA damage
      of brain neurons caused by arsenic through the RNS signal pathway.

PMID- 20804629
TI  - Effects of taurine on male reproduction in rats of different ages.
AB  - BACKGROUND: It has been demonstrated that taurine is one of the most abundant
      free amino acids in the male reproductive system, and can be biosynthesized by
      male reproductive organs. But the effect of taurine on male reproduction is
      poorly understood. METHODS: Taurine and beta-alanine (taurine transport
      inhibitor) were offered in water to male rats of different ages. The effects of
      taurine on reproductive hormones, testis marker enzymes, antioxidative ability
      and sperm quality were investigated. RESULTS: The levels of T and LH were
      obviously increased by taurine supplementation in rats of different ages, and the
      level of E was also significantly elevated in baby rats. The levels of SOD, ACP,
      SDH and NOS were obviously increased by taurine administration in adult rats, but
      the levels of AKP, AST, ALT and NO were significantly decreased. The levels of
      SOD, ACP, LDH, SDH, NOS, NO and GSH were significantly elevated by taurine
      administration in aged rats, but the levels of AST and ALT were significantly
      decreased. The motility of spermatozoa was obviously increased by taurine
      supplement in adult rats. The numbers and motility of spermatozoa, the rate of
      live spermatozoa were significantly increased by taurine supplement in aged rats.
      CONCLUSIONS: The present study demonstrated that a taurine supplement could
      stimulate the secretion of LH and T, increase the levels of testicular marker
      enzymes, elevate testicular antioxidation and improve sperm quality. The results
      imply that taurine plays important roles in male reproduction especially in aged
      animals.

PMID- 20804628
TI  - Neuro-endocrine basis for altered plasma glucose homeostasis in the Fragile X
      mouse.
AB  - BACKGROUND: The fragile X mouse model shows an increase in seizure
      susceptibility, indicating an involvement of the GABAergic system via an
      alteration in cellular excitability. In the brain, we have previously described a
      reduction in GABAA receptor expression as a likely basis for this susceptibility.
      In the brains of fragile X mice, this reduction in receptor expression culminates
      with a concomitant increase in the expression of glutamic acid decarboxylase
      (GAD), the enzyme responsible for GABA synthesis. Further, voltage-sensitive
      calcium channel expression is reduced in the pancreas of the fragile X mouse.
      Since there are considerable similarities in the GABAergic system in the brain
      and pancreas, we evaluated the protective role of taurine in pancreatic islet
      development in both wild type (WT) and fragile X mice (KO). METHODS: One-month
      old FVB/NJ males or age-matched fmr1-knockout (KO) mice were supplemented with
      taurine in drinking water (0.05% w/v) for four weeks. Age-matched controls were
      fed water only for the same duration. At four weeks, mice were sacrificed and
      pancreases processed for histology and immunohistochemical studies on changes of
      insulin, glucagon and somatostatin expression. Additional mice were subjected to
      a glucose tolerance test. RESULTS: Taurine treatment resulted in a significant
      increase in the number and size of islets. WT taurine-fed mice, slightly
      hypoglycemic prior to glucose injection, showed significantly reduced plasma
      glucose at 30 min post-injection when compared to control mice. KO mice had
      normal baseline plasma glucose concentration; however, following glucose
      injection they had higher plasma glucose levels at 30 min when compared to
      controls. Supplementation of taurine to KO mice resulted in reduced baseline
      levels of plasma glucose. After glucose injection, the taurine-fed KO mice had
      reduced plasma glucose at 30 min compared to KO. Concomitant with the increased
      islets size and glucose tolerance observed in taurine-fed mice there was an
      increase in insulin, glucagon and somatostatin immunoreactivity in the islets of
      WT mice. In the KO mice however, insulin levels were not affected whereas
      glucagon and somatostatin levels were reduced. Exocytosis of these hormones is
      calcium-dependent, therefore any exacerbation of calcium homeostasis could affect
      hormone release. We found the expression of the voltage sensitive calcium
      channels (VSCC) is drastically reduced in the pancreas of fragile X mice.
      CONCLUSIONS: During early development, the VSCC play an important role in calcium
      dependent gene expression. Since these channels are also involved in
      depolarization and calcium-mediated vesicular release of neurotransmitters and
      pancreatic hormones, alterations in the expression of VSCC not only will affect
      calcium-mediated gene expression but also hormonal and neurotransmitter release
      creating therefore a neuroendocrine perturbation in the fragile X that may
      potentially affect other organ systems. We find that in the fragile X mouse,
      taurine treatment may partially restore functionality of the neuro-endocrine
      pancreas.

PMID- 20804631
TI  - Basal energy expenditure in southern Chinese healthy adults: measurement and
      development of a new equation.
AB  - The objective of the present study is to measure basal energy expenditure (BEE)
      using the Cosmed K4b2 portable metabolic system (Rome, Italy) and to develop a
      new predictive equation for BEE in southern Chinese adults. A total of 165
      healthy Chinese adults aged 18-45 years with normal body weight were involved in
      the present study. BEE was measured by Cosmed K4b2. Body composition was
      determined by body composition analysers (ImpediMed DF50, QLD, Australia).
      Multiple linear regression analysis and correlation analysis were applied to
      develop a new optimal equation for predicting BEE of southern healthy Chinese
      adults. Measured BEE (mBEE) of southern Chinese healthy adults was 5513 (sem 96)
      kJ/d, which was similar to the results predicted by the equation developed by of
      Liu 5579 (sem 57) kJ/d (P = 0.37) and significantly lower than those from
      equations developed by Henry (5763 (sem 54) kJ/d), Schofield (5898 (sem 58) kJ/d)
      and Harris-Benedict (HB; 5863 (sem 51) kJ/d) (all P = 0.001). The optimal
      equation developed by our data was BEE (kJ/d) = 277+89 weight (kg)+600 sex (male
      = 1 and female = 0) (r2 = 0.48, n 165). For males, BEE (kJ/d) = 105 weight (kg) -
      58 (r2 = 0.27, n 79); for females, BEE (kJ/d) = 69 weight (kg)+1335 (r2 = 0.24, n
      86). In conclusion, the mBEE of southern Chinese healthy adults was 5513 (sem 96)
      kJ/d. The BMR of Chinese adults of normal weight is overestimated by widely used
      prediction equations developed by Henry, Schofield and HB. The equation developed
      in the present study (equation 7) can be used in predicting BEE for Chinese
      adults aged 18-45 years with normal body weight.

PMID- 20804630
TI  - The effectiveness of dried cranberries ( Vaccinium macrocarpon) in men with lower
      urinary tract symptoms.
AB  - Lower urinary tract symptoms (LUTS) are a common condition in older men. The
      objective of the present study was to evaluate the efficacy and tolerability of
      cranberry (Vaccinium macrocarpon) powder in men at risk of prostate disease with
      LUTS, elevated prostate-specific antigen (PSA), negative prostate biopsy and
      clinically confirmed chronic non-bacterial prostatitis. Forty-two participants
      received either 1500 mg of the dried powdered cranberries per d for 6 months
      (cranberry group; n 21) or no cranberry treatment (control group; n 21). Physical
      examination, International Prostate Symptom Score, quality of life (QoL), five
      item version of the International Index of Erectile Function (IIEF-5), basic
      clinical chemistry parameters, haematology, Se, testosterone, PSA (free and
      total), C-reactive protein (CRP), antioxidant status, transrectal ultrasound
      prostate volume, urinary flow rate, ultrasound-estimated post-void residual urine
      volume at baseline, and at 3 and 6 months, and urine ex vivo anti-adherence
      activity were determined in all subjects. In contrast to the control group,
      patients in the cranberry group had statistically significant improvement in
      International Prostate Symptom Score, QoL, urination parameters including voiding
      parameters (rate of urine flow, average flow, total volume and post-void residual
      urine volume), and lower total PSA level on day 180 of the study. There was no
      influence on blood testosterone or serum CRP levels. There was no statistically
      significant improvement in the control group. The results of the present trial
      are the first firm evidence that cranberries may ameliorate LUTS, independent of
      benign prostatic hyperplasia or C-reactive protein level.

PMID- 20804632
TI  - Factors influencing the vitamin D status of 10-year-old urban South African
      children.
AB  - OBJECTIVE: Assessment of vitamin D status in a cohort of healthy 10-year-old
      urban children and the factors that influence vitamin D status in these children.
      DESIGN: A cross-sectional study. Blood samples were collected across four seasons
      of the year for the biochemical determination of serum 25-hydroxyvitamin D
      [25(OH)D]. Anthropometric measurements (height and weight), BMI and total fat and
      lean mass (determined by the dual energy X-ray absorptiometry) were measured.
      25(OH)D concentrations were assessed by chemiluminescent assay. SETTING: Study of
      children in the Greater Johannesburg area of South Africa who form the Bone
      Health sub-cohort of the longitudinal Birth to Twenty cohort. SUBJECTS: Three
      hundred and eighty-five children who form the Bone Health sub-cohort of the
      longitudinal Birth to Twenty cohort. RESULTS: White children had significantly
      higher 25(OH)D than their black peers (120.0 (sd 36.6) nmol/l v. 93.3 (sd 34.0)
      nmol/l, respectively). Seasonal variations in 25(OH)D levels were found only in
      white children, with 25(OH)D levels being significantly higher in white than in
      black children during the autumn and summer months. In multiple regression
      analysis, season, ethnicity, sex and total fat mass were the factors found to
      have an influence on 25(OH)D. Vitamin D deficiency (7 %) and insufficiency (19 %)
      were uncommon among the 10-year-old children. CONCLUSIONS: Vitamin D
      supplementation or fortification is not warranted in healthy children living in
      Johannesburg. However, further studies need to confirm this in other regions of
      the country, especially in those living further south and with less sunshine
      during the winter months.

PMID- 20804633
TI  - Use of FAO food balance sheets to estimate the potential ability of novel folate
      enriched eggs to increase the folate supply in European Union countries.
AB  - OBJECTIVE: European governments have yet to introduce mandatory folic acid
      fortification of foods for neural tube defect prevention because of uncertainty
      about the long-term safety of high intake of folic acid. Novel folate-enriched
      eggs have been proposed as offering a practical way of increasing intake of
      natural folates, which do not have the same safety concerns as synthetic folic
      acid. Our objective was to estimate the potential increase in folate supply that
      could occur in European Union (EU) countries if normal eggs were replaced by
      folate-enriched eggs. DESIGN: FAOSTAT data on daily per capita availability of
      eggs were linked to mean folate concentrations of un-enriched and folate-enriched
      eggs from three representative feeding trials from the recent literature.
      SETTING: Data were collated in Microsoft Excel. SUBJECTS: The study used food
      balance sheets for Europe for 1961-2003 and for twenty-six individual EU
      countries for 2003. RESULTS: There has been little variation in egg supply in
      Europe over the past 40 years, with eggs providing only about 1.3-1.6 % of total
      energy. In 2003, the average per capita egg supply across twenty-six EU countries
      was 32.8 g/d, equivalent to a little over half an egg. Even if the folate
      concentrations of all eggs across the EU were increased two- to threefold, per
      capita folate supply would increase only by about 25 MUg/d. CONCLUSIONS: At
      current enrichment levels, the availability of novel folate-enriched eggs will
      have little impact on folate supply in EU countries. In the absence of mandatory
      fortification, additional natural folate sources are needed urgently.

PMID- 20804634
TI  - D-stem: a parallel electron diffraction technique applied to nanomaterials.
AB  - An electron diffraction technique called D-STEM has been developed in a
      transmission electron microscopy/scanning transmission electron microscopy
      (TEM/STEM) instrument to obtain spot electron diffraction patterns from
      nanostructures, as small as ~3 nm. The electron ray path achieved by configuring
      the pre- and postspecimen illumination lenses enables the formation of a 1-2 nm
      near-parallel probe, which is used to obtain bright-field/dark-field STEM images.
      Under these conditions, the beam can be controlled and accurately positioned on
      the STEM image, at the nanostructure of interest, while sharp spot diffraction
      patterns can be simultaneously recorded on the charge-coupled device camera. When
      integrated with softwares such as GatanTM STEM diffraction imaging and Automated
      Crystallography for TEM or DigistarTM, NanoMEGAS, the D-STEM technique is very
      powerful for obtaining automated orientation and phase maps based on diffraction
      information acquired on a pixel by pixel basis. The versatility of the D-STEM
      technique is demonstrated by applying this technique to nanoparticles, nanowires,
      and nano interconnect structures.

PMID- 20804635
TI  - Microfluidic system for transmission electron microscopy.
AB  - We present a microfluidic system that maintains liquid flow in a specimen chamber
      for scanning transmission electron microscope (STEM) imaging. The specimen
      chamber consists of two ultrathin silicon nitride windows supported by silicon
      microchips. They are placed in a specimen holder that seals the sample from the
      vacuum in the electron microscope and incorporates tubing to and from the sample
      connected to a syringe pump outside the microscope. Using results obtained from
      fluorescence microscopy of microspheres flowing through the system, an equation
      to characterize the liquid flow through the system was calibrated. Gold
      nanoparticles of diameters of 30 and 100 nm moving in liquid were imaged with a
      200 kV STEM. It was concluded that despite strong influences from Brownian
      motion, and sensitivity to small changes in the depth of the bypass channel, the
      electron microscopy flow data matched the calculated flow speed within an order
      of magnitude. The system allows for rapid (within a minute) liquid exchange,
      which can potentially be used, for example, to investigate the response of
      specimens, e.g., eukaryotic or bacterial cells, to certain stimuli.

PMID- 20804636
TI  - Effects of the carbon coating and the surface oxide layer in electron probe
      microanalysis.
AB  - Effects related with the attenuation and deflection suffered by an electron beam
      when it passes through a carbon conductive coating and an oxide film layer on the
      surface of bulk samples are studied by Monte Carlo simulations and energy
      dispersive spectroscopy with electron excitation. Analytical expressions are
      provided for the primary beam energy and intensity losses and for the deflection
      of the incident electrons in both layers, in terms of the incidence energy, the
      film mass thicknesses, and the atomic number of the oxidized element. From these
      analytical expressions, suitable corrections are proposed for the models used to
      describe the X-ray spectrum of the substrate, including also the contribution of
      the X-rays generated in the oxide and conductive films and the characteristic X
      ray absorption occurring in those layers. The corrections are implemented in a
      software program for spectral analysis based on a routine of parameter
      refinement, and their influence is studied separately in experimental spectra of
      single-element standards measured at different excitation energies. Estimates for
      the layer thicknesses are also obtained from the spectral fitting procedure.

PMID- 20804637
TI  - Scanning electron and confocal scanning laser microscopy imaging of the
      ultrastructure and viability of vaginal Candida albicans and non- albicans
      species adhered to an intrauterine contraceptive device.
AB  - Although bacterial biofilms have been studied in detail, adhesion of Candida
      albicans and non-albicans species to an intrauterine contraceptive device (IUD)
      is not clear. The objective of this study was to evaluate aspects of imaging of
      the ultrastructure and viability of vaginal yeasts adhered to different parts of
      an IUD, through scanning electron microscopy (SEM) and confocal scanning laser
      microscopy (CSLM). We studied yeasts isolated from different patients with
      vulvovaginal candidiasis: C. albicans, C. glabrata, C. guillermondii, C.
      parapsilosis, C. tropicalis, and Saccharomyces cerevisiae. A suspension of the
      each yeast was prepared and incubated with IUD parts (tail, without copper, and
      copper-covered). SEM and CSLM showed that all the vaginal yeasts adhered to all
      the parts of the IUD and demonstrated viability, including 30 days after contact
      for C. albicans. Possibly irregularities of IUD surface contribute to the
      adherence process. Although all of the IUD parts contribute to retention of
      yeasts in the genital tract, high concentration of yeast cells on the tail may
      indicate the importance of this segment in maintaining the colonization by yeast
      cells because the tail forms a bridge between the external environment, the
      vagina that is colonized by yeast cells, and the upper genital tract where there
      is no colonization.

PMID- 20804638
TI  - Diffraction imaging in a He+ ion beam scanning transmission microscope.
AB  - The scanning helium ion microscope has been used in transmission mode to
      investigate both the feasibility of this approach and the utility of the signal
      content and the image information available. Operating at 40 keV the penetration
      of the ion beam, and the imaging resolution achieved, in MgO crystals was found
      to be in good agreement with values predicted by Monte Carlo modeling. The bright
      field and annular dark-field signals displayed the anticipated contrasts
      associated with beam absorption and scattering. In addition, the diffraction of
      the He ion beam within the sample gave rise to crystallographic contrast effects
      in the form of thickness fringes and dislocation images. Scanning transmission He
      ion microscopy thus achieves useful sample penetration and provides nanometer
      scale resolution, high contrast images of crystalline materials and crystal
      defects even at modest beam energies.

PMID- 20804639
TI  - Dilution and magnification effects on image analysis applications in activated
      sludge characterization.
AB  - The properties of activated sludge systems can be characterized using image
      analysis procedures. When these systems operate with high biomass content,
      accurate sludge characterization requires samples to be diluted. Selection of the
      best image acquisition magnification is directly related to the amount of biomass
      screened. The aim of the present study was to survey the effects of dilution and
      magnification on the assessment of aggregated and filamentous bacterial content
      and structure using image analysis procedures. Assessments of biomass content and
      structure were affected by dilutions. Therefore, the correct operating dilution
      requires careful consideration. Moreover, the acquisition methodology comprising
      a 100* magnification allowed data on aggregated and filamentous biomass to be
      determined and smaller aggregates to be identified and characterized, without
      affecting the accuracy of lower magnifications regarding biomass
      representativeness.

PMID- 20804640
TI  - Suberized cell walls of cork from cork oak differ from other species.
AB  - Plants have suberized cells that act as protective interfaces with the
      environment or between different plant tissues. A lamellar structure of
      alternating dark and light bands has been found upon transmission electron
      microscopy (TEM) observation of cork cells and considered a typical feature of
      the suberized secondary wall. We observed cork cells from periderms of Quercus
      suber, Quercus cerris, Solanum tuberosum, and Calotropis procera by TEM after
      uranyl acetate and lead citrate staining. A lamellated structure was observed in
      S. tuberosum and C. procera but not in Q. suber and Q. cerris where the suberized
      cell wall showed a predominantly hyaline aspect with only a dark dotted staining.
      Removal of suberin from Q. suber cells left a thinner secondary wall that lost
      the translucent aspect. We hypothesize that the species' specific chemical
      composition of suberin will result in different three-dimensional macromolecular
      development and in a different spatial location of lignin and other aromatics. A
      lamellated ultrastructure is therefore not a general feature of suberized cells.

PMID- 20804641
TI  - X-ray mapping and scatter diagram analysis of the discoloring products resulting
      from the interaction of artist's pigments.
AB  - The discoloring interaction between the artist's pigments cadmium yellow and the
      copper-containing malachite, an interaction that is conjectured to cause black
      spotting in oil paintings of the 19th and early 20th centuries, was examined
      using X-ray mapping and scatter diagram analysis. The application of these
      coupled techniques confirmed that copper sulfide phases were produced during
      discoloration reaction. Scatter diagram analysis indicated that two copper
      sulfide stoichiometries (CuS and Cu3S2) were present as reaction products where
      previously only crystalline CuS (covellite) had been identified by X-ray
      diffraction. The results demonstrate the potential of X-ray mapping coupled with
      scatter diagram analysis for the identification of both crystalline and X-ray
      amorphous phases produced by such complex heterogeneous interactions and their
      applicability to the investigation of interactions of artists' pigments.

PMID- 20804642
TI  - Intra-species variability in ITS-1 sequences of Haemonchus contortus isolated
      from goats in West Bengal, India.
AB  - This study evaluated the existence of different genotypes of Haemonchus contortus
      prevailing among goats in West Bengal, India. These parasites were isolated from
      the abomasum of goat intestine and the molecular characterization was performed
      by comparing variation of nucleotide sequences of the internal transcribed spacer
      1 (ITS-1) gene region. Single-strand conformation polymorphism (SSCP) analysis of
      ITS-1 amplified product showed the presence of three distinct conformations both
      in male and female parasites. The sequence analysis of conformations showed two
      single nucleotide polymorphisms (SNP) in male parasites at nucleotide positions
      106 and 107 and one SNP was detected in female parasites at nucleotide position
      157. These nucleotide variations in different isolates did not alter the interior
      loop structure of the predicted secondary RNA, therefore we believe these
      variations may not be responsible for any evolutionary changes among
      conformations. 

PMID- 20804643
TI  - [An apparatus for bone marrow access: a way to establish rapid access to the
      circulation].

PMID- 20804644
TI  - [An investigation of Gram-positive bacteria infection in an intensive care unit
      during 6 years].
AB  - OBJECTIVE: To retrospectively investigate the risk factors, distribution,
      antibiotic resistance of infection with Gram-positive (G+) bacteria in an
      intensive care unit (ICU), so as to provide the reference for clinical prevention
      and treatment. METHODS: A retrospective analysis of clinical data of 83 patients
      with G+ bacteria infection in ICU from January 2003 to December 2008 was done.
      RESULTS: Of the 125 strains of G+ bacteria from 83 patients, Staphylococcus was
      the main organism (63.2%, 79/125). The prognosis of the patient was related with
      surgical operation (chi2=9.107, P=0.003), gastric intubation (chi2=4.053,
      P=0.044), complication (chi2 5.908, P=0.015) and the use of immunosuppressant
      (chi2=5.761, P=0.016). Multi-bacterial infection was related with surgery
      (chi2=8.847, P=0.003) and tracheostomy (chi2=10.445, P=0.001). The antibiotic
      susceptibility test in vitro showed that G+ bacteria displayed multi-resistance
      to antibiotics, but all of G+ bacteria were sensitive to vancomycin (resistance
      rate was 0). CONCLUSION: Staphylococcus was the most common pathogen of G+
      bacterial infection in ICU. Further surveillance of bacterial resistance is
      warranted in ICU, and antimicrobial drugs should be used according to the result
      of susceptibility test. Taking account of the antibiotic resistance and risk
      factors of G+ bacteria infection in ICU, the infection could be controlled and
      the death rate could be cut down when appropriate measures are taken.

PMID- 20804645
TI  - [The monitoring and its clinical significance of the hydrogen peroxide and
      interleukin-6 levels in exhaled breath condensate of chronic obstructive
      pulmonary diseases patients undergoing mechanical ventilation].
AB  - OBJECTIVE: To explore the relationship of inflammatory response of the
      respiratory tract and prognosis of chronic obstructive pulmonary diseases (COPD)
      patients undergoing mechanical ventilation (MV) in respiratory intensive care
      unit (RICU). METHODS: Thirty patients with COPD undergoing MV were involved in
      the study, and divided into survival group (n=16) and non-survival group (n=14).
      Exhaled breath condensate (EBC) was collected on day 1, 3, 5, 7 after MV. The
      concentration of hydrogen peroxide (H2O2) in EBC was measured fluorimetrically.
      The content of interleukin-6 (IL-6) in EBC was measured by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: (1) The significantly lower H2O2 and IL-6
      levels in the survival group were observed on days 3, 5 and 7 compared with those
      of day 1 after MV [H2O2 (micromol/L): 0.10+/-0.03 , 0.06+/-0.03, 0.04+/-0.03 vs.
      0.19+/-0.14, IL-6 (ng/L): 11.11+/-2.39, 10.35+/-2.09, 8.89+/-2.63 vs. 14.45+/
      6.03, all P<0.05]. A significantly lower H2O2 level was observed on day 7
      compared with that of day 3 (P<0.05). (2) A significantly higher H2O2 level in
      the non-survival group was observed on days 5 and 7 compared with that of day 1
      (0.16+/-0.15, 0.25+/-0.16 vs. 0.05+/-0.03, both P<0.05). A significantly higher
      IL-6 level was observed on days 3, 5 and 7 compared with that of day 1 (9.36+/
      2.38, 10.55+/-2.33, 14.05+/-4.23 vs. 6.87+/-3.47, all P<0.05). The significantly
      higher H2O2 and IL-6 levels in non-survival group were observed on day 7 compared
      with those of days 3 and 5 (all P<0.05). (3) The significantly lower H2O2 and IL
      6 levels in non-survivors were observed on day 1 after MV compared with survivors
      (both P<0.05). There were no marked differences in levels of H2O2 and IL-6
      between non-survivors and survivors on day 3 (both P>0.05). A significantly
      higher H2O2 level in non-survivors was observed compared with survivors on day 5
      (P<0.05). In addition, the significantly higher H2O2 and IL-6 levels in non
      survivors were observed on day 7 compared with survivors (both P<0.05). (4) The
      levels of H2O2 and IL-6 in EBC in survivors and non-survivors undergoing MV
      showed no correlation with acute physiology and chronic health evaluation II
      (APACHEII) and APACHEIII scores (both P>0.05). CONCLUSION: The findings suggest
      that the levels of H2O2 and IL-6 in EBC are correlated with prognosis of patients
      undergoing MV, and it may prove to be useful in monitoring inflammatory response
      in the airway after MV as a guidance of therapy and prognosis in COPD patients
      undergoing MV.

PMID- 20804646
TI  - [Analysis of risk factors related to mortality of patients with community
      acquired pneumonia due to methicillin-resistant Staphylococcus aureus].
AB  - OBJECTIVE: To describe the clinical features of reported cases of community
      acquired pneumonia (CAP) due to methicillin-resistant Staphylococcus aureus
      (MRSA), and to evaluate the risk factors related to outcome. METHODS: A
      systematic search of databases from January 1995 to December 2009 was performed.
      Baseline characteristics of survivors and non-survivors in the hospital were
      compared with the chi2 test for categorical variables. Variables with P<0.2 were
      entered in Logistic regression. Survival analysis was estimated by the Kaplan
      Meier method according to use of antimicrobials inhibiting toxin production.
      RESULTS: Fifty-two articles were identified reporting data on 74 patients, with
      41.1% of total mortality, short duration of symptom onset to death [(6.1+/-11.0)
      days], and prolonged hospital admissions [(28.6+/-29.1) days]. Logistic
      regression analysis showed that influenza like symptoms (P=0.04), hemoptysis
      (P<0.01), leucopenia (P<0.01) were the risk factors associated with death, and
      using clindamycin or linezolid which could inhibit the Panton-Valentine
      leukocidin (PLV, P<0.01) was the factor associated with survival. Kaplan-Meier
      analysis indicated that the antibiotic therapies inhibiting toxin production were
      associated with improved outcome in these cases (chi2=21.59, P<0.01). CONCLUSION:
      CAP due to MRSA is a severe disease with significant lethality. Empiric therapy
      of severe CAP with flu-like symptoms, hemoptysis and leucopenia should include
      coverage for MRSA. Targeted treatment with antimicrobials inhibiting toxin
      production appear to be more appropriate selection.

PMID- 20804647
TI  - [Effect of hydrogen sulfide on rat pulmonary artery reactivity and injury induced
      by lipopolysaccharide].
AB  - OBJECTIVE: To explore the effects of hydrogen sulfide (H2S) on abnormal pulmonary
      artery reactivity and injury induced by lipopolysaccharide (LPS). METHODS:
      Seventy-two rats were divided into four groups randomly according to table of
      random number: control group, LPS group, sodium hydrosulfide (NaHS) as a donor of
      H2S+LPS group and NaHS+normal saline (NS) group (n=18 in each group). Rats were
      challenged with 0.8 ml/kg LPS (200 microg/200 microl) by intratracheal
      instillation. NaHS (28 micromol/kg, 0.5 ml) was injected intraperitoneally 10
      minutes before LPS instillation and 2 hours after LPS instillation. Twelve hours
      later, 6 rats from each group were sacrificed. Blood from carotid artery was
      collected to detect H2S content in serum. After that, pulmonary artery rings
      (PARs) were prepared carefully, then the contraction response of PARs to
      phenylephrine (PE, 10(-6) mol/L) and the endothelium-dependent relaxation
      response to acetylcholine (ACh, 10(-6) mol/L) were measured using isolated
      vascular ring tension detecting technique. Six rats from each group were
      sacrificed for determination of malondialdehyde (MDA) content of pulmonary
      artery, and the remaining 6 rats from each group were sacrificed for observation
      of morphological changes in pulmonary artery tissue. RESULTS: Compared with
      control group, after LPS instillation, the contraction response (g/mg) of PARs to
      PE increased greatly (0.86+/-0.20 vs. 0.56+/-0.13), the relaxation response to
      ACh significantly decreased [(65.18+/-7.05)% vs. (84.13+/-8.84)%]. MDA content
      (mmol/L) in pulmonary artery tissues increased (32.03+/-7.81 vs. 5.82+/-0.92),
      and H2S (micromol/L) content in serum decreased (175.23+/-27.36 vs. 238.12+/
      16.38). Changes of all results were significant (P<0.05 or P<0.01). The pulmonary
      artery tissue and endothelium were injured. However, these changes were reversed
      by administration of NaHS intraperitoneally, the contraction response of PARs to
      PE decreased [(0.61+/-0.17) g/mg], the relaxation response to ACh increased
      [(82.92+/-9.71)%], MDA content in pulmonary artery tissue decreased [(16.88+/
      3.54) mmol/L] and H2S content in serum increased [(242.70+/-38.80) micromol/L].
      There was significant difference in all results (P<0.05 or P<0.01). The injury to
      the tissue induced by LPS were alleviated significantly. There was no statistical
      difference in above indexes between NaHS+NS group and control group, except for
      the level of H2S. CONCLUSION: Exogenous H2S could not only reverse abnormal
      vascular reactivity of PARs induced by LPS but also alleviate the injury to
      pulmonary artery tissue induced by LPS.

PMID- 20804648
TI  - [Protective effect of N-acetylcysteine on hyperoxic lung injury and its relation
      with p38 mitogen-activated protein kinase signaling pathway].
AB  - OBJECTIVE: To investigate the expression of p38 mitogen-activated protein kinase
      (MAPK) in hyperoxic lung injury (HLI), and explore the protective effect of N
      acetylcysteine (NAC) on HLI and its mechanism. METHODS: Thirty Wistar rats aged 3
      weeks old were divided into five groups with 6 rats in each group according to
      random digits table: room-air group (A), hyperoxia injury group (B),
      hyperoxia+NAC group (C), hyperoxia+p38 MAPK inhibitor (SB203580) group (D),
      hyperoxia+NAC+SB203580 group (E). Rats in NAC groups were injected with NAC (200
      mg/kg) intraperitoneally, and they received an intravenous injection of SB203580
      (0.5 mg/kg) in SB203580 groups. The animals were sacrificed after 7 days of
      experiment. Lung pathology and grade of lung tissue injury were examined with
      light microscopy, lung wet/dry (W/D) ratio, total protein (TP) level in
      bronchoalveolar lavage fluid (BALF) and permeability coefficient were evaluated.
      The location and quantity of phosphorylation p38 MAPK (p-p38 MAPK) protein were
      detected by immunohistochemistry and Western blotting analysis respectively.
      RESULTS: The pathological changes in the lung in B group included severe alveolar
      oedema with inflammatory cells aggregation and red blood cell leakage, while the
      lung pathological pictures in C, D, E groups were improved significantly compared
      with B group. p-p38 MAPK positive cells increased in B group compared with those
      in A group, involving many types of pulmonary cells, especially in infiltrating
      inflammatory cells. In C, D, E groups, the positive cells remarkably decreased
      compared with B group. p-p38 MAPK content was higher in B group than that in A
      group (0.20+/-0.03 vs. 0.11+/-0.01, P<0.05), and p-p38 MAPK expressions in C, D,
      E groups decreased significantly compared with B group (0.16+/-0.02, 0.15+/-0.01,
      0.14+/-0.02 vs. 0.20+/-0.03, all P<0.05), but were higher than those in A group
      (all P<0.05). There was no significant difference in p-p38 MAPK quantity among
      three groups. Changes in W/D ratio, TP and permeability coefficient among groups
      were comparable with those of p-p38 MAPK protein quantity. CONCLUSION: Reactive
      oxygen species (ROS) activated p38 MAPK signaling pathway. NAC may exert a
      protective effect on HLI through attenuation of hyperoxia-induced p38 MAPK
      activation.

PMID- 20804649
TI  - [The comparison of the vasoactive effects of dopamine on isolated rabbit
      pulmonary and systemic arteries after incubation with lipopolysaccharide].
AB  - OBJECTIVE: To compare the vasoactive effects of dopamine (DOPA) of different
      concentrations on isolated rabbit pulmonary and systemic arteries after
      incubation with lipopolysaccharide (LPS). METHODS: Six white male rabbits were
      used. Thirty-six pulmonary arterial rings and 36 systemic arterial rings were
      prepared. The 36 pulmonary arterial rings were divided into six groups to
      determine the effect of different concentrations of DOPA (4x10(-5) , 8x10(-5),
      16x10(-5) micromol/L) on the tension of the normal pulmonary artery (PN-DOPA4, PN
      DOPA8, PN-DOPA16 groups, respectively), and the tension of the pulmonary artery
      rings after being incubated with LPS (PL-DOPA4, PL-DOPA8, PL-DOPA16 groups,
      respectively). The 36 systemic arterial rings were also divided into six groups
      as the pulmonary arterial rings, including normal groups (SN-DOPA4, SN-DOPA8 , SN
      DOPA16) and LPS groups (SL-DOPA4, SL-DOPA8 , SL-DOPA16). RESULTS: (1) DOPA
      relaxed the arterial rings in PN-DOPA4 and SN-DOPA4 groups, while it produced
      contraction in PN-DOPA8, PN-DOPA16, SN-DOPA8 and SN-DOPA16 groups, and the
      contraction was more marked with the increase in concentration of DOPA. (2) After
      preincubation with LPS, the relaxation property of DOPA in PL-DOPA4 and SL-DOPA4
      groups was observed to be reversed to contraction [(22.60+/-6.68)% vs. -(2.25+/
      0.58)%, (3.80+/-0.52)% vs. -(3.65+/-0.75)%, P<0.05 and P<0.01]; the contraction
      response of DOPA in PL-DOPA8 group decreased compared with PN-DOPA8 group by
      (14.52+/-0.59)% (P<0.05), while increased by (25.90+/-1.75)% in SL-DOPA8 group
      compared with SN-DOPA8 group (P<0.05), and no response was observed in PL-DOPA16
      and SL-DOPA16 groups. (3)After preincubation with LPS, changes in pulmonary
      arterial tension (PL/PN) in DOPA4 group were more obvious than those in systemic
      arterial tension (SL/SN, -10.90+/-5.06 vs. -1.00+/-0.24, P<0.05), while the SL/SN
      in DOPA8 group were more obvious (1.80+/-0.35 vs. 0.48+/-0.17, P<0.01).
      CONCLUSION: DOPA in low concentrations had the function of relaxation on the
      pulmonary arterial and systemic arterial rings. After the arterial rings are
      preincubated with LPS, the relaxation response of DOPA of low concentrations is
      changed to be vaso-contraction, and the changes in pulmonary arterial rings are
      most marked. DOPA of different concentrations all produce contraction effect on
      LPS-preincubated arterial rings.

PMID- 20804650
TI  - [The dynamic alteration in Gq/11 protein expression in multiple organs during
      acute respiratory distress syndrome in rat].
AB  - OBJECTIVE: To observe the dynamic alteration in Gq/11 protein expression in the
      lung, brain, heart, kidney, liver and small intestine of rats suffering from
      acute respiratory distress syndrome (ARDS), and to explore the pathophysiological
      mechanism of ARDS in terms of signal transduction. METHODS: Forty male Wistar
      rats were randomly divided into oleic acid (OA) groups (n=32) and control group
      (n=8). OA groups included four subgroups: 30, 60, 90, 120 minutes (each n=8). An
      ARDS model in rats was reproduced by intravenous injection of OA 0.2 ml/kg in 2
      minutes, and control group was given normal saline by the same way. Lactate
      dehydrogenase (LDH), malondialdehyde (MDA) and angiotensin converting enzyme
      (ACE) in the plasma and the above-mentioned organs were measured. G alpha q/11
      protein expression in these organs was examined by Western blotting. RESULTS:
      Compared with control group, LDH activity in the plasma and the heart 30 minutes
      after injection of OA gradually increased [plasma (kU/L): 9.69+/-1.66 vs. 6.27+/
      1.70, heart (kU/g): 0.81+/-0.12 vs. 0.59+/-0.09], and in the lung, brain, kidney,
      and small intestine 60 minutes after injection of OA also gradually increased
      [lung (kU/g): 1.15+/-0.19 vs. 0.87+/-0.11, brain (kU/g): 2.27+/-0.37 vs. 1.53+/
      0.61, kidney (kU/g): 1.13+/-0.26 vs. 0.64+/-0.09, small intestine (kU/g): 0.72+/
      0.10 vs. 0.60+/-0.13], and in the liver (kU/g) 90 minutes after injection of OA
      gradually increased (0.50+/-0.14 vs. 0.39+/-0.05, P<0.05 or P<0.01). MDA
      concentration in the heart (micromol/g) 30 minutes after injection of OA
      gradually increased (2.20+/-0.47 vs. 1.45+/-0.27), and in the plasma, lung and
      kidney 60 minutes after injection of OA gradually increased [ plasma
      (micromol/L): 3.10+/-0.58 vs. 2.33+/-0.35, lung (micromol/g): 5.56+/-1.30 vs.
      2.05+/-0.52, kidney (micromol/g): 1.61+/-0.27 vs. 0.98+/-0.42], and in the brain,
      liver and small intestine 90 minutes after injection of OA gradually increased
      [brain (micromol/g): 6.78+/-1.38 vs. 5.83+/-1.58, liver (micromol/g): 2.58+/-0.68
      vs. 2.11+/-0.42, small intestine (micromol/g): 2.14+/-0.51 vs. 0.81+/- 0.26,
      P<0.05 or P<0.01]. ACE activity was reduced in the plasma and lung 60 minutes
      after injection of OA [ plasma (micromolxmin(-1)xL(-1)): 15.47+/-1.68 vs. 19.87+/
      3.11, lung(micromolxmin(-1)xg(-1)): 20.61+/-1.81 vs. 26.26+/-1.93], but in the
      kidney (micromolxmin(-1)xg(-1)) it was gradually increased (15.92+/-1.20 vs.
      13.67+/-2.26), and in the small intestine (micromolxmin(-1)xg(-1)) 90 minutes
      after injection of OA it gradually increased (4.42+/-0.34 vs. 3.29+/-0.24, all
      P<0.01). G alpha q/11 protein expression in the lung and small intestine
      obviously increased 30 minutes after injection of OA [lung: (119.24+/-2.38)% vs.
      (100.00+/-18.74)%, small intestine: (138.91+/-23.03)% vs. (100.00+/-19.43)%], and
      in the brain, heart and kidney increased 60 minutes after injection of OA [brain:
      (141.85+/-33.82)% vs. (100.00+/-16.81)%, heart: (124.72+/-24.05)% vs. (100.00+/
      16.04)%, kidney: (123.98+/-25.74)% vs. (100.00+/-8.50)%], and in the liver
      increased 90 minutes after injection of OA [(134.34+/-19.14)% vs. (100.00+/
      13.04)%, P<0.05 or P<0.01]. A positive correlation between the change in G alpha
      q/11 protein expression and LDH in these organs (r=0.584, P<0.05) was found.
      CONCLUSION: Up-regulation of Gq/11 protein expression in the lung, brain, heart,
      kidney, liver and small intestine may induce abnormal activity of phosphatidyl
      inositol signal transduction and thus plays a role in the production of multiple
      organ injury during ARDS.

PMID- 20804651
TI  - [Prognostic implication of plasma N-terminal-pro-brain natriuretic peptide in
      weaning from mechanical ventilation].
AB  - OBJECTIVE: To explore the relationship between plasma N-terminal-pro-brain
      natriuretic peptide (NT-proBNP) levels of patients before weaning and outcome of
      weaning from mechanical ventilation (MV) in patients. METHODS: A total of 126
      intensive care unit (ICU) patients with MV were enrolled from August 2008 to
      December 2009, and the cause composition was recorded. Plasma NT-proBNP levels
      were measured in patients with MV, in whom the clinical data had fulfilled the
      criteria for weaning from MV, spontaneous breathing trial, weaning and extubation
      were performed successively. The enrolled patients were divided into two groups
      namely success group and failure group according to weaning outcome within 48
      hour. The plasma NT-proBNP levels in two groups were compared, and receiver
      operating characteristic (ROC) curve for predicted weaning outcome was plotted to
      find the cut-off point value of NT-proBNP. RESULTS: The major causes of MV were
      pulmonary infection (33.3%) and surgical operations (30.2%), and heart failure
      accounted for only 11.9%. The plasma NT-proBNP levels before weaning were
      negatively correlated with the consequences of weaning. The plasma NT-proBNP
      levels in failure group (n=38) were significantly higher than those in success
      group (n=88, lg NT-proBNP: 3.97+/-0.48 vs. 2.99+/-0.67 ,P<0.05). The NT-proBNP
      area under ROC curve was 0.875+/-0.043 [95% confidence interval (95% CI) was
      0.792-0.959]. The cut-off point value which could be used to predict the outcome
      of weaning was 3 914.5 ng/L. The sensitivity and specificity of the cut-off point
      value were 78.3% and 91.1%, respectively. CONCLUSION: Irrespective of the causes
      of institution of MV, the cardiac function must be considered as an important
      factor in affecting the outcome of weaning. The plasma NT-proBNP level of 3 914.5
      ng/L can be used to predict weaning outcome. The cardiac function should be
      improved to a point within the range of cut-off point value in order to improve
      the success rate of weaning.

PMID- 20804653
TI  - [The protective effect of keratinocyte growth factor on lipopolysaccharide
      induced acute lung injury in rat].
AB  - OBJECTIVE: To investigate the protective effect of keratinocyte growth factor
      (KGF) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and its
      potential mechanism in rats. METHODS: Thirty-six Sprague-Dawley (SD) rats were
      randomly divided into three groups, each group with 12 rats. LPS (5 mg/kg) was
      injected intravenously to induce ALI in model group, and same amount of normal
      saline was injected in control group and KGF group. The rats in KGF group were
      treated with KGF (5 mg/kg) intratracheally after injection of LPS. The rats were
      sacrificed after 8 hours, histologic assessments, wet/dry weight (W/D) ratio,
      pulmonary vascular permeability, lung epithelial cell permeability, the
      proliferation and repair capacity of type II alveolar epithelial cells (ATII)
      were analyzed. RESULTS: Under optical microscope, it was found that KGF could
      reduce injury to lung tissue induced by LPS. Compared with the model group, KGF
      could decrease pulmonary vascular permeability [(0.026+/-0.049)% vs. (0.087+/
      0.027)%], lung epithelial cell permeability [(0.692+/-0.017)% vs. (0.931+/
      0.029)%] and W/D ratio (4.778+/-0.243 vs. 6.869+/-0.153, P<0.05 or P<0.01),
      enhance the proliferation and repair capacity of ATII cells (ATII cells: 6.083+/
      1.781 vs. 4.666+/-1.923, injury area (mm2): 2.946+/-0.453 vs. 6.181+/-0.975,
      P<0.05 and P<0.01). CONCLUSION: KGF could reduce the injury to the lung in LPS
      induced ALI, and it plays a protective role through enhancing the proliferation
      and repair capacity of ATII cells.

PMID- 20804654
TI  - [The changes in plasma insulin and C-peptide levels in patients with obstructive
      sleep apnea hypopnea syndrome and their clinical significance].

PMID- 20804655
TI  - [Effect of intraosseous infusion on patients with heart arrest for recovery of
      spontaneous circulation].

PMID- 20804656
TI  - [The signification of glucose-regulated protein 78 expression on cardiomyocytes
      ischemia/reperfusion].

PMID- 20804663
TI  - Development of a five-year mortality model in systemic sclerosis patients by
      different analytical approaches.
AB  - OBJECTIVES: Systemic sclerosis (SSc) is a multiorgan disease with high mortality
      rates. Several clinical features have been associated with poor survival in
      different populations of SSc patients, but no clear and reproducible prognostic
      model to assess individual survival prediction in scleroderma patients has ever
      been developed. METHODS: We used Cox regression and three data mining-based
      classifiers (Naive Bayes Classifier [NBC], Random Forests [RND-F] and logistic
      regression [Log-Reg]) to develop a robust and reproducible 5-year prognostic
      model. All the models were built and internally validated by means of 5-fold
      cross-validation on a population of 558 Italian SSc patients. Their predictive
      ability and capability of generalisation was then tested on an independent
      population of 356 patients recruited from 5 external centres and finally compared
      to the predictions made by two SSc domain experts on the same population.
      RESULTS: The NBC outperformed the Cox-based classifier and the other data mining
      algorithms after internal cross-validation (area under receiving operator
      characteristic curve, AUROC: NBC=0.759; RND-F=0.736; Log-Reg=0.754 and Cox=
      0.724). The NBC had also a remarkable and better trade-off between sensitivity
      and specificity (e.g. Balanced accuracy, BA) than the Cox-based classifier, when
      tested on an independent population of SSc patients (BA: NBC=0.769, Cox=0.622).
      The NBC was also superior to domain experts in predicting 5-year survival in this
      population (AUROC=0.829 vs. AUROC=0.788 and BA=0.769 vs. BA=0.67). CONCLUSIONS:
      We provide a model to make consistent 5-year prognostic predictions in SSc
      patients. Its internal validity, as well as capability of generalisation and
      reduced uncertainty compared to human experts support its use at bedside.
      Available at: http://www.nd.edu/~nchawla/survival.xls.

PMID- 20804664
TI  - Non-traumatic osteonecrosis of the femoral head - from clinical to bench.
AB  - Non-traumatic osteonecrosis of the femoral head commonly affects young adults
      between the third and fifth decade of life. It is the leading cause of hip joint
      replacements in many Asian countries including Taiwan. The ultimate goal is the
      preservation of the involved hip. However, this is often challenging since early
      diagnosis is difficult, the etiologies are miscellaneous, the pathogenesis is
      unclear, and successful treatment is undetermined. As a consequence, this disease
      remains well-known but not fully-understood. This review provides an update of
      the progress from clinical studies to basic bench work in terms of natural
      history, risk factors, genetic predilections, diagnosis, staging, and
      miscellaneous therapeutic modalities.

PMID- 20804665
TI  - Surgical management of recurrent nasopharyngeal carcinoma.
AB  - Current standard treatment of nasopharyngeal carcinoma (NPC) is either
      radiotherapy alone or combined chemoradiotherapy. Surgery in the form of
      nasopharyngectomy is usually only offered when there is evidence of local
      recurrence or persistent disease. Recurrent NPC (rNPC) can be detected earlier
      with the utilization of Epstein-Barr virus molecular diagnosis. This may result
      in early management with salvage surgery and hence improved survival. The facial
      translocation approach enhanced our ability to access the nasopharynx. Through a
      multidisciplinary approach with the collaboration of neurosurgeons, the surgical
      indication of salvage surgery is extended. This allowed improved respectability
      in locally advanced disease and involved the skull base and intracranial
      extension with reasonable morbidity and mortality. Endoscopic nasopharyngectomy
      is a choice for recurrent NPC with central roof or floor lesions with minimal
      lateral extension. Multivariate analysis indicated that gender, parapharyngeal
      space involvement, surgical margin, and the modality of adjuvant therapy impact
      significantly on local control. The impact on survival is indicated by the dura
      or brain involvement, local recurrence and modality of adjuvant therapy. It is
      apparent that recurrent NPC patients who underwent surgery had a significantly
      better survival rate than the re-radiation therapy group.

PMID- 20804666
TI  - Prediction of major complications after isolated coronary artery bypass grafting:
      the CGMH experience.
AB  - BACKGROUND: The in-hospital mortality of coronary artery bypass grafting (CABG)
      is low but can be significant if catastrophic complications occur. To increase
      the safety of CABG, we aimed to establish a predictive model of major
      postoperative complications that incorporated patient characteristics and
      operative strategies. METHODS: A retrospective study was performed which included
      all consecutive patients receiving isolated CABG from August 2006 to February
      2008 (n = 319). Patient characteristics were quantified by the additive
      EuroSCORE. Operative strategies were classified as cardioplegic arrest, on-pump
      beating, and off-pump. RESULTS: Four major complications were identified to be
      connected to the in-hospital mortality: (1) requirement of mechanical circulatory
      supports > 72 h (odds ratio [OR] 28.9, 95% confidence interval [CI] 6.0-139.9),
      (2) requirement of mechanical ventilator supports > 72 h (OR 9.5., 95%, CI 2.2-
      42.7), (3) acute renal failure requiring dialysis (OR 9.2, 95% CI 2.2-38.3), (4)
      major gastrointestinal complications (OR 5.4., 95% CI 1.1-26.7). An increase of
      additive EuroSCORE (OR 1.2, 95% CI 1.1-1.4) and the cardioplegic strategy (OR
      2.7, 95% CI 1.2-6.0) were independent risk factors for major complications. The
      probability of one or more major complication was > 50% for patients receiving
      cardioplegic CABG with an additive EuroSCORE > 8. CONCLUSION: Dependence on the
      mechanical ventilator or circulatory supports > 72 h, acute renal failure
      requiring dialysis, and major gastrointestinal complications were major
      complications of CABG. The individual risk of having at least one of these
      complications could be predicted by the patient's preoperative EuroSCORE and
      operative strategy. A surgical plan tailored by institutional experiences on
      specific risk factors and aggressive therapeutic plans for major complications
      are helpful in improving the overall results of CABG.

PMID- 20804667
TI  - The application of miniprobe ultrasonography in the diagnosis of colorectal
      subepithelial lesions.
AB  - BACKGROUND: Difficulty with the proximal lesion approach and durability of
      endoscopic ultrasonography (EUS) instruments usually limits its application for
      lower gaotrointestina (GI) lesions to locoregional staging of rectal cancer. This
      study investigated the value of colonoscopic miniprobe ultrasonography for
      differential diagnosis and treatment strategy in patients with colorectal
      subepithelial lesions (SEL). METHODS: Miniprobe ultrasonography was Performed in
      40 consecutive patients with suspected colorectal SEL or residual lesions after
      endoscopic resection at one medical center by the same endoscopist (C-J Lin). The
      EUS images and procedure records were reviewed. The final diagnosis of these
      lesions was confirmed by cross section imaging, histopathologic findings, or
      clinical follow-up. RESULTS: Miniprobe EUS allowed high-resolution imaging and a
      successful approach to all colorectal SEL through the working channel of a
      sigmoidoscope or colonoscope without breakdown of the miniprobe. Thirteen
      patients, suspected of having rectal carcinoid tumors (mean size, 6.9 +/- 3.3
      mm), were treated radically by endoscopic mucosal resection using a transparent
      cap (EMRC) after EUS confirmation of no muscular invasion. Three patients had no
      residual or recurrent carcinoid tumor on EUS examination after previous empiric
      polypectomy or biopsy. EUS detected submucosal lipomas (mean size, 18.5 mm;
      range, 8.6-25.6 mm) in ten patients however, only two patients underwent
      endoscopic resection. Five patients had suspected rectal myogenic stromal tumors
      on EUS; three were transferred for surgical resection due to uterine myoma
      compression (N = 2) or mucinous adenocarcinoma of the appendix with rectal
      metastasis (N = 1), and two had uterine myoma detected by gynecologic ultrasound
      or CT. One appendiceal stone with orifice obstruction mimicking cecal submucosal
      tumor was proved by surgical resection. One patient had hemorrhoids proved by
      hemorrhoidectomy. One patient was proved to have proctitis cystica profunda by
      EMRC. The other six patients had various benign lesions, which were diagnosed and
      followed-up by EUS without progression. In thirty-five of forty patients (88%)
      colorectal SEL were managed uneventfully according to EUS interpretation.
      CONCLUSIONS: Miniprobe ultrasonography can be a useful supplement to routine
      colonoscopy and provide treatment guidance for suspected colorectal subepithelial
      lesions.

PMID- 20804668
TI  - Skin grafting as a salvage procedure in diabetic foot reconstruction to avoid
      major limb amputation.
AB  - BACKGROUND: Bone and tendons exposure in diabetic patients requires flap
      reconstruction to avoid major limb amputation. However, for critical and unstable
      diabetic patients, revascularization and flap reconstruction may not be feasible.
      Skin grafts can be used in such a situation, and the purpose of this study is to
      evaluate this procedure in terms of treatment outcome. METHODS: From October 2003
      to October 2006, there were 73 critical diabetic cases with bone and tendon
      exposure at the lower extremities. Repeated debridements were performed to remove
      the exposed tendon and burr the bare bone until bleeding. Some cases needed
      adjuvant therapy to promote granulation for skin grafting. RESULTS: Before skin
      grafting, thirty cases need toe amputation. The mean presurgical preparation
      period for a suitable granulation bed was 38.4 days. After skin grafting, wound
      healing was achieved within 4 weeks in 54 cases, and it took over 4 weeks in 9
      cases. In 2 cases, a second skin graft was required.Forefoot stump revision was
      performed in 3 cases. Total wound healing could not be achieved within 3 months
      in 5 cases. The complete wound healing rate was 74% in 1 month and 86.3% in 2
      months. CONCLUSION: In order to preserve the feet, the skin grafting rather than
      major amputation is suitable for critical and unstable diabetic patients. The
      drawback is the relatively prolonged treatment course.

PMID- 20804669
TI  - The experience of parathyroidectomy when treating primary parathyroid
      hyperplasia.
AB  - BACKGROUND: Total parathyroidectomy with forearm autograft (TP) and subtotal
      parathyroidectomy (SP) are the two widely-accepted surgical procedures for
      treating primary parathyroid hyperplasia. Although TP carries an increased risk
      of permanent hypoparathyroidism and implantation site recurrence, it is still the
      preferred option of some surgeons. This retrospective study's aim is to confirm
      the superiority of initial TP when treating primary multiple gland hyperplasia.
      METHODS: All patients who had received parathyroidectomy for primary multiple
      gland hyperplasia from 1987 to 2007 were reviewed. Two modalities of
      parathyroidectomy were used; these were subtotal parathyroidectomy (3 (1/2), SP)
      as the standard initial treatment strategy and TP for disease recurrence or
      synchronous thyroid abnormality. RESULTS: A total of 14 patients were treated and
      these had a median follow-up period of 98 months (range, 51~216). Among these
      patients, 11 received SP and 3 underwent TP. Seven out of the 11 SP patients
      (63%) developed postoperative disease recurrence. Of the seven patients who
      received neck re-exploration, six (85%) demonstrated temporary postoperative
      hypocalcemia compared with the first operation (14%) (p = 0.003). Four of these
      patients (57%) experienced recurrent laryngeal nerve palsy, which was
      significantly higher than the rate after the first operation (0%) (p = 0.006).
      Therefore, cervical reexploration carried a significantly elevated overall
      complication rate compared to initial neck exploration (p = 0.002). Of the three
      initial TP patients, one showed recurrence at the implantation site. All eight
      recurrence cases underwent re-operations that significantly reduced their serum
      calcium concentrations (12.55 to 8.7 mg/dL, p = 0.008) and parathyroid hormone
      levels (135 to 70 pg/mL, p = 0.008) compared with their respective levels just
      before re-exploration; this group had a 10-year recurrence-free rate of 45%.
      CONCLUSION: Re-operations for recurrent disease are common regardless of the type
      of primary surgery. Compared with initial TP, re-operation for post-SP disease
      recurrence was associated with a significantly higher complication rate. TP would
      seem to be recommended as the choice of initial surgical procedure.

PMID- 20804670
TI  - Comparison of developmental pattern change in preschool children with spastic
      diplegic and quadriplegic cerebral palsy.
AB  - BACKGROUND: This study compares the longitudinal change of developmental patterns
      in preschool children with spastic diplegic (SD) and spastic quadriplegic (SQ)
      cerebral palsy (CP). METHODS: Sixty children with spastic CP, aged 1-5 years (3.2
      +/- 1.2 years), were classified into 2 groups: SD (n = 29) and SQ (n = 31). Gross
      Motor Function Classification System (GMFCS) levels were classified during the
      initial assessments. Developmental profiles, including development quotients
      (DQs) of gross motor, fine motor, expressive language, concept comprehension,
      situation comprehension, self help, personal social and general development, were
      evaluated on initial and final assessments and an average of one year later. The
      DQ change index (%) was calculated as 100% x (final DQ - initial DQ)/initial DQ.
      RESULTS: Children with SQ had lower DQs in all developmental functions than those
      with SD on both assessments (p < 0.01). The DQ distributions of developmental
      profiles were different in SD and SQ groups, although both groups displayed the
      lowest DQs in the gross motor domain. As indicated by the DQ change index, most
      DQs increased with age in children with SD; however, most decreased with age in
      children with SQ (p < 0.05). CONCLUSION: These findings suggest different CP
      subtypes demonstrate various development profiles. The evolvement of
      developmental patterns with age was different in children with various CP
      subtypes.

PMID- 20804671
TI  - Factors associated with motor speech control in children with spastic cerebral
      palsy.
AB  - BACKGROUND: Speech production is often impaired in children with cerebral palsy
      (CP). This study investigated the factors associated with motor speech control in
      children with spastic cerebral palsy. METHODS: Thirty-three children with spastic
      CP who were able to speak were identified for this study. They were classified
      into two groups: group A (spastic diplegia or hemiplegia, n = 17) and group B
      (spastic quadriplegia, n = 16). Each child received various assessments, namely
      cognition, language, modified Verbal Motor Production Assessment for Children
      (VMPAC), speech intelligibility, CP subtype, and Gross Motor Function
      Classification System (GMFCS). RESULTS: Group A showed better cognition and
      language function, higher modified VMPAC scores and better GMFCS levels than
      group B (p < 0.05). However, the two groups did not significantly differ in
      speech intelligibility. Linear regression indicated that all modified VMPAC
      scores were negatively related to CP subtype (adjusted r2 = 0.51~0.63, p <
      0.001). The average modified VMPAC scores had a positive relationship with global
      language scores (adjusted r2 = 0.63, p < 0.001), and the modified VMPAC scores of
      the sequence subtests were positively related to the full intelligence quotients
      (adjusted r2 = 0.55, p < 0.001). CONCLUSION: The findings of this study suggest
      that motor impairment severity, cognition and language functions are associated
      with the motor speech control among children with CP.

PMID- 20804672
TI  - Treatment of branch retinal vein occlusion induced macular edema in treatment
      naive cases with a single intravitreal triamcinolone or bevacizumab injection.
AB  - BACKGROUND: To evaluate the effects of a single intravitreal injection of
      triamcinolone acetonide (ivTA) or bevacizumab (ivBe) on visual acuity and central
      macular thickness (CMT) in cases of macular edema secondary to branch retinal
      vein occlusion (BRVO) for eyes that are treatment-naive. METHODS: This
      consecutive, retrospective, nonrandomized, clinical interventional study included
      83 patients (83 eyes) with macular edema secondary to BRVO who received single
      ivTA (25 patients) or ivBe (24 patients) injections, or no treatment (controls,
      34). The main outcomes included CMT measurements using optical coherence
      tomography (OCT) and best-corrected visual acuity (BCVA). RESULTS: CMT decreased
      significantly from baseline at 4, 8, 12 and 24 weeks after treatment (p < 0.05)
      in both the intravitreal groups and the control group. BCVA improved
      significantly from baseline at 4 and 8 weeks after treatment among the ivTA group
      (p < 0.05) and at 4, 8 and 12 weeks after treatment among the ivBe group (p <
      0.05). Comparing CMT between the groups, significant differences were found
      between ivTA and control groups and ivBe and control groups at the 4- and 8- week
      checkpoints (p < 0.05). Significant differences were found in BCVA only between
      ivBe and control groups at the 8-week checkpoint (p = 0.049). No significant
      differences were found for CMT and BCVA between the ivBe and ivTA groups (p >
      0.05) at any checkpoint after treatment. No patient experienced immediate
      procedure-related complications or any obvious systemic adverse events in either
      the ivTA group or the ivBe group. Delayed complications included steroid induced
      ocular hypertension in eight eyes (32%) and development of posterior subcapsular
      cataracts in five eyes (28%) in the ivTA group. CONCLUSIONS: Both the ivTA and
      ivBe therapies were beneficial short-term treatment options for the treatment of
      macular edema secondary to BRVO. However, the ivBe treatment appears to be safer
      and less prone to adverse side effects such as ocular hypertension and cataract
      compared with ivTA therapy.

PMID- 20804673
TI  - Developmental profiles and mentality in preschool children with Prader-Willi
      syndrome: a preliminary study.
AB  - BACKGROUND: A majority of the children with Prader-Willi syndrome (PWS) have
      global developmental delay and mental delay. The aim of this study was to
      investigate the developmental profiles and mental assessments among preschool
      children with PWS. METHODS: Ten children with PWS between the ages of 15 months
      to 6 years, and 11 children with typical development were enrolled. Developmental
      profiles in terms of their developmental quotient (DQ) for the eight domains of
      the Chinese Children Developmental Inventory (CCDI) and mental assessments in
      terms of intelligence quotient (IQ) and developmental index (DI) were carried out
      for all children. RESULTS: The DQs of all eight domains, including gross motor,
      fine motor, expressive language, concept comprehension, situation comprehension,
      self help, personal- social and general development, in the PWS group were lower
      than the DQs of the children from the typical development group (p < 0.01).
      Children with PWS had better DQs in the fine motor domain than in the gross motor
      domain and in the receptive language domain than in the expressive language
      domain. Furthermore, their verbal IQ were better than their performance IQ and
      their mental DI was better than their psychomotor DI. CONCLUSIONS: These findings
      suggest that the children with PWS show an uneven global developmental delay
      together with an uneven mental delay. The results of this study should allow
      clinicians to better understand the developmental functioning of children with
      PWS and this will help with the planning of treatment strategies.

PMID- 20804674
TI  - Conscious sedation reduces patient discomfort and improves satisfaction in
      flexible bronchoscopy.
AB  - BACKGROUND: Conscious sedation for patients undergoing flexible bronchoscopy (FB)
      is suggested to alleviate discomfort and improve satisfaction despite controversy
      regarding its benefits. In Taiwan, the general FB practice involves local
      anesthesia only. This study aimed to assess the benefits and risks of conscious
      sedation in diagnostic FB. METHODS: This prospective case control study enrolled
      44 non-sedated and 44 sedated patients who underwent diagnostic FB. All received
      the standard upper airway preparation, while sedated patients received clinically
      judged increments of midazolam and alfentanil for conscious sedation. Patient
      discomforts and the operator's opinions during FB were assessed using the verbal
      analogue score (VAS, 0-10 scale). Willingness to return was assessed as five
      scales to monitor patient satisfaction. Safety profiles throughout the procedures
      were also assessed. RESULTS: Compared to non-sedated patients, sedated ones
      expressed less discomfort, with lower VAS scores regarding scope insertion (3.5
      [0-10] vs. 0 [0-5], p < 0.001), cough (5 [0-10] vs. 0 [0-5], p < 0.001), dyspnea
      (3 [0-10] vs. 0 [0-8], p < 0.001), pain (3 [0-10] vs. 0 [0-5], p < 0.001), and
      global tolerance of the procedures (5 [1-10] vs. 0 [0-9], p < 0.001). More
      sedated patients expressed willingness to return (70.5% vs. 36.4%, p = 0.001).
      The bronchoscopist also rated lower VAS scores on cough and dyspnea in sedated
      patients. Sedated patients had less hypertension but more hypoxemic episodes
      during the procedure, which were all transient and not life-threatening.
      CONCLUSIONS: Conscious sedation with clinically judged midazolam and alfentanil
      reduces discomforts, improves satisfaction, and carries slight, but manageable,
      hypoxemia risks in patients undergoing FB.

PMID- 20804675
TI  - Long-term survivors of adult rhabdomyosarcoma of maxillary sinus following
      multimodal therapy: case reports and literature reviews.
AB  - Rhabdomyosarcoma of the maxillary sinus is uncommon in adults. The clinical
      course and appropriate treatment strategy for the disease remains to be
      elucidated. This article describes two adult patients with rhabdomyosarcoma of
      the maxillary sinus who achieved long-term survival after undergoing multimodal
      therapy. We also reviewed the literature regarding 23 patients who were 15 years
      of age or older and had rhabdomyosarcoma of the maxillary sinus and were treated
      between 1950 and 2000. Results of our analysis suggest that multimodal therapy
      may become the mainstay treatment for adult rhabdomyosarcoma of the maxillary
      sinus. We believe that adequate surgical procedures, planned radiotherapy,
      aggressive chemotherapeutic agents and the best supportive care for complications
      may improve the prognosis of patients with this disease.

PMID- 20804676
TI  - Physeal change after tuberculous osteomyelitis of the long bone in children.
AB  - BACKGROUND: Tuberculous osteomyelitis of the long bone in children is often
      neglected, and established transphyseal bone lesions are common. The purpose of
      this study was to evaluate the clinical outcomes of these patients. METHODS:
      Between January 1990 and December 2008, 19 patients (10 boys and 9 girls) with
      sustained tuberculous osteomyelitis of the long bone accompanied by physeal
      involvement were treated at our institute. The average age was 23.8 months
      (range, 10-58 months). All patients received surgical treatment and
      antituberculosis therapy for at least 6 months. The final radiographic and
      functional results were analyzed. RESULTS: All patients were followed up for an
      average of 61.8 months (range, 14-123 months). The most common site of infection
      was the distal femur (8 patients, 42.1%), followed by the proximal tibia (5
      patients, 26.3%) and the distal tibia (3 patients, 15.8%). Most of the lesions
      were osteolytic, round to oval in shape, and showed marginal sclerosis. Some
      lesions were expanding or multiloculated. The periosteal reaction was minimal.
      Even in cases with extensive surgical curettage through the physis, the growth
      plate maintained its function and gradually remodeled. Clinical symptoms improved
      within 4-6 weeks. All bone lesions decreased in size in 3-6 months. Further,
      physeal bar formation was observed, but the extent was minimal. All transphyseal
      lesions healed gradually over a period of several years. Good remodeling of
      skeletal lesions was noted. CONCLUSIONS: The diagnosis of tuberculous
      osteomyelitis of the long bone should be considered in every child with
      unexplained chronic limb pain or swollen limbs. The lesions are usually located
      in the metaphysis and easily cross the growth plate to the epiphysis. Surgical
      debridement is beneficial in both diagnosis and treatment. In patients with
      growth plate involvement, careful surgical debridement is recommended to
      eradicate infection since the risk of permanent physeal damage is minimal. The
      physis can heal gradually, and full range of motion of the adjacent joints can be
      maintained.

PMID- 20804677
TI  - Micropapillary variant of urothelial carcinoma: a report of 4 cases and
      literature review.
AB  - Micropapillary variant of urothelial carcinoma (MPUC) is an uncommon variant of
      urothelial carcinoma with high metastatic potential. The cases reported in the
      literature were associated with high grade and advanced stages of the disease at
      presentation and had a poor prognosis. Four patients were diagnosed with MPUC at
      our center. One patient had an MPUC located in the urinary bladder, and the other
      three had MPUC originating from the kidney and/or the ureter respectively. All
      these lesions were confirmed pathologically and treated by radical surgery. Three
      of the four patients were found to be in the advanced stages of the disease.
      Although adjuvant chemotherapy was administered, the first and second patients
      died after 15 and 10 months, respectively. The third and fourth patients are
      being followed up at our hospital 5 and 27 months after surgery, respectively.
      Clinically, MPUC is far more aggressive than conventional urothelial carcinoma.
      Patients with MPUC should be diagnosed promptly and treated aggressively.

PMID- 20804678
TI  - Clinical pathway for melanoma detection using comprehensive cutaneous analysis
      with Melanoscan.
AB  - The usefulness of a comprehensive cutaneous photography system (Melanoscan) was
      tested using the following parameters: 1) decision to screen pathway, 2) clinical
      pathway, 3) clinical outcome, and 4) patient acceptance. The results indicate
      that 55 percent of those with criteria for scanning were reimbursed by insurance
      (AMA CTP category 1 code status 96904 for total body photography). In this model
      of whole body scanning, the ratio of time demand on physicians, patients, and
      technicians is 1:8:12. In 53 patients, 394 lesions of concern were identified. Of
      these lesions, 48 (12.31%) were scars, 306 (78.46%) were changed, and 36 (9.23%)
      were new. The decision to biopsy was made for 18 of the 394 lesions analyzed in
      the follow-up studies. Sensitivity of the process in determining malignant
      lesions is 75.00 percent and specificity is 73.70 percent. Preliminary results
      suggest that change detection analysis reduces the number of biopsies and
      improves diagnostic accuracy. Assessment of survey results revealed a high degree
      of patient satisfaction with ease of following Melanoscan directions (81.25%), as
      well as overall satisfaction with the process (73.44%). These results suggest
      that whole body screening using the Melanoscan provides a device in which
      accuracy of lesion tracking, patient confidence in lesion documentation, and
      clinician time are optimized.

PMID- 20804679
TI  - Cutaneous angiogenesis in patient with intravascular lymphoma (IVL): A case
      report.
AB  - We present a case of widespread cutaneous telangiectasias in a patient with a B
      cell intravascular lymphoma most likely representing tumor-induced angiogenesis.
      The patient presented with a rapid onset of large cutaneous telangiectasias and
      skin edema, followed by the development of multiorgan failure. We describe
      difficulties with the ante-mortem diagnosis in the patient with predominant,
      clinically observed, skin lesions. The patient had disseminated disease involving
      many organs with a rapidly fatal outcome. The final diagnosis of intravascular
      malignant lymphoma (IVL) was established post-mortem after morphological and
      immunohistochemical studies of the autopsy material.

PMID- 20804680
TI  - Osseous metaplasia late in the course of nephrogenic systemic fibrosis.
AB  - Osseous metaplasia has recently been described in several cases of nephrogenic
      systemic fibrosis, sometimes in association with unusual clinical features such
      as painful hyperkeratotic spicules, palpable bony masses, and disease regression.
      Some authors have suggested that it may mainly occur late in the disease course
      or even be a marker for involuting nephrogenic systemic fibrosis. Here, we
      present a 27-year-old woman with a 7-year history of nephrogenic systemic
      fibrosis, who developed cutaneous osseous metaplasia.

PMID- 20804681
TI  - Ulcerated plaque under a ruby ring in an immunosuppressed patient.
AB  - We report a primary inoculation fungal infection in a 76-year-old man with acute
      myeloid leukemia. The patient presented with a painful red plaque located where
      he routinely wore a ruby ring. Histopathology revealed multiple branching septate
      hyphae. Cultures confirmed Fusarium and Candida parapsilosis infection. A short
      discussion of these organisms follows.

PMID- 20804682
TI  - Ichthyosiform sarcoidosis: A case report and review of the literature.
AB  - Sarcoidosis is a potentially life-threatening, multisystem, granulomatous disease
      that can present with cutaneous manifestations in patients. A rare cutaneous
      manifestation of this disease may resemble acquired ichthyosis. We report a 45
      year-old woman with a several year history of dyspnea on exertion and panuveitis
      who presented to a county hospital with acquired lower extremity ichthyosis and a
      biopsy consistent with both acquired ichthyosis and noncaseating, granulomatous
      sarcoidosis. To our knowledge, this entity has been described in only 22 previous
      independent cases, with the present case being 1 of only 5 cases to rapidly
      progress to full systemic involvement. Furthermore, it is important to recognize
      the manifestations of sarcoidosis in the skin, because these may be the
      presenting signs of systemic illness.

PMID- 20804683
TI  - CHILD syndrome with thrombocytosis and congenital dislocation of hip: A case
      report from India.
AB  - Congenital Hemidysplasia with Ichthyosiform Nevus and Limb Defects (CHILD) is a
      very rare entity inherited as an X-linked trait. The cutaneous lesions are
      characteristic and usually involve the right side of the body. We report a case
      of CHILD syndrome in an Indian child affecting the left side with various other
      associations not yet described in the literature, such as thrombocytosis and
      congenital dislocation of the hip. The rarity of the syndrome prompted us to
      report this case.

PMID- 20804685
TI  - Paraneoplastic Acanthosis Nigricans: The importance of exhaustive and repeated
      malignancy screening.
AB  - Paraneoplastic acanthosis nigricans (P-AN) characteristically has a sudden onset,
      rapid progression, and extensive cutaneous involvement. The association between P
      AN and internal malignancy is well established and the most common association is
      with adenocarcinoma of gastrointestinal origin. We present the case of an 81-year
      old man with a 12-month history of anorexia, weight loss, and clinical evidence
      of extensive acanthosis nigricans. After exhaustive and repeated investigations a
      papillary thyroid carcinoma and a follicular adenoma were identified and he
      improved upon its resection. To our knowledge, P-AN in association with thyroid
      neoplasm has been reported on only one previous occasion.

PMID- 20804684
TI  - Mucogingival overgrowth in a geriatric patient.
AB  - Epulis fissuratum is a pathological condition caused by an ill-fitting denture.
      The mucogingival hyperplasia may be considered as a reactive condition of the
      oral mucosa to excessive mechanical pressure on the mucosa. Epulis fissuratum
      excision is a procedure usually done for prosthodontic reasons. The treatment of
      this benign entity is essential mainly for masticatory reasons. The use of diode
      laser for epulis removal without infiltrated anesthesia in a conscious geriatric
      patient is currently under investigation.

PMID- 20804686
TI  - Oral lichen planus in childhood: A rare case report.
AB  - Oral lichen planus is a cell-mediated immune condition and is infrequently
      encountered in children, with a prevalence of about 0.03 percent in childhood.
      Reports of oral lichen planus affecting children are scarce in the literature.
      The purpose of this article is to present a rare case of oral lichen planus
      affecting a seven-year-old child without concomitant cutaneous lesions. Intraoral
      lesions and associated mild discomfort treated with topical corticosteroid
      therapy and a plaque control regime resulted in a favorable result.

PMID- 20804687
TI  - Homogeneous blue pattern: A rare presentation in an acral congenital melanocytic
      nevus.
AB  - Acral melanocytic nevi are relatively frequent in the palmoplantar location. In
      congenital nevi various characteristic dermoscopic patterns have been described,
      such as reticular and globular patterns, brown pigmented areas, and areas with
      peripilar depigmentation. However, there are few reports on the dermoscopic
      pattern of acral congenital nevi. The homogeneous blue pattern is typical of blue
      nevus and is not typical of acral localization and metastasis of cutaneous
      melanoma. However, this pattern should be considered characteristic of acral
      congenital nevus.

PMID- 20804688
TI  - A nodulo-ulcerative lesion on the nose.
AB  - Lupus vulgaris (LV) is a chronic, progressive, and potentially destructive form
      of cutaneous tuberculosis commonly seen in previously sensitized individuals with
      moderate to high immunity. We present a case of LV located on the nose of an 84
      year-old female patient, discuss the diagnosis and treatment modalities, and
      emphasize the importance of having a high index of suspicion for this condition.

PMID- 20804689
TI  - Epidermodysplasia verruciformis after cutaneous T-cell lymphoma: Periungual
      presentation.
AB  - Epidermodysplasia verruciformis (EV) has several clinical presentations and has
      been reported in various states of immune deregulation. We report the unique
      presentation of this disease as a pigmented periungual macule in a patient with a
      previous history of immune deregulation related to cutaneous lymphoma. A
      literature review did not reveal any previous reports of EV in patients with
      cutaneous T-cell lymphoma.

PMID- 20804690
TI  - Clinico-histopathological correlation and the treatment response of 20 patients
      with cutaneous tuberculosis.
AB  - Cutaneous tuberculosis (TB) can mimic other granulomatous diseases clinically and
      histopathologically. This case series relates images and workup of 20 patients
      who were histopathologically and therapeutically confirmed to have cutaneous TB.
      Although positive results of ESR, Mantoux reactivity, and TB cultures facilitate
      the clinical diagnosis, negative results should not exclude the diagnosis of
      cutaneous TB. An alternative cause should be considered if the clinical response
      to anti-TB drugs is inapparent within 2 months.

PMID- 20804691
TI  - Elephantiasis nostras verrucosa on the abdomen of a Turkish female patient caused
      by morbid obesity.
AB  - Elephantiasis Nostras Verrucosa is a rare disorder of an extremity or a body
      region, which is associated with chronic lymphedema. There are 7 reported cases
      of abdominal elephantiasis in the medical literature. Here we report a morbidly
      obese female patient with elephantiasis nostras verrucosa on the abdominal wall.

PMID- 20804692
TI  - Successful treatment of superficial pyoderma gangrenosum associated with
      hidradenitis suppurativa with adalimumab.
AB  - Pyoderma gangrenosum (PG) and hidradenitis suppurativa (HS) are chronic
      inflammatory dermatoses that can be a challenge to treat. A role for TNF-alpha in
      their pathogenesis has been postulated in the literature. A therapeutic benefit
      of infliximab has been reported in recalcitrant cases of both conditions. To
      date, there is less evidence about the use of adalimumab for these conditions. We
      report a patient with severe superficial PG on a background of HS, which
      responded to adalumimab therapy after failure of infliximab therapy.

PMID- 20804693
TI  - [A new case of nevus oligemicus].
AB  - Nevus oligemicus is a rare lesion characterized by selective vasoconstriction of
      the deep dermal vascular plexus compared with the superficial one. It has been
      suggested that it may be caused by increased sympathetic tone in the deep dermal
      vascular plexus or an abnormality of hormone receptors, which is why it is
      considered a functional nevus. Clinically, it presents as an asymptomatic, fixed,
      livid erythematous macule with a striking decrease in local temperature compared
      with surrounding healthy skin. CASE REPORT: We report the case of a 59-year-old
      man with a 2-year history of three large areas of persistent and asymptomatic
      livid erythema on trunk and flanks. These areas blanched under light pressure.
      Measurement of the surface temperature of the patch revealed a decrease of up to
      2.5 degrees C with respect to surrounding skin. Histology showed superficial
      dermal capillary dilatation without other significant findings. The fixed nature
      of the lesions, consistent histopathology, and the finding of localized
      hypothermia allowed the diagnosis of nevus oligemicus. CONCLUSIONS: The diagnosis
      is mainly clinical. Our case is the eleventh case of nevus oligemicus reported in
      the literature.

PMID- 20804694
TI  - Raised diastolic pressure as an early predictor of left ventricular remodeling
      after infarction: should echocardiography or natriuretic peptides be used for
      assessment?

PMID- 20804695
TI  - Cocaine-associated chest pain and acute myocardial infarction.

PMID- 20804696
TI  - The complexity of the association between socioeconomic status and acute
      myocardial infarction.

PMID- 20804697
TI  - Value of NT-ProBNP level and echocardiographic parameters in ST-segment elevation
      myocardial infarction treated by primary angioplasty: relationships between these
      variables and their usefulness as predictors of ventricular remodeling.
AB  - INTRODUCTION AND OBJECTIVES: To assess the value of N-terminal fragment of brain
      natriuretic peptide (NT-proBNP) measurement and echocardiography for predicting
      ventricular remodeling after myocardial infarction and to investigate
      relationships between the NT-proBNP level and echocardiographic parameters at
      discharge and in the medium term. METHODS: The study involved 159 patients with
      myocardial infarction treated by primary coronary angioplasty. The NT-proBNP
      level was measured on admission, at discharge and after 6 months.
      Echocardiography was performed at discharge and after 6 months. RESULTS: Overall,
      31 patients (19.5%) demonstrated remodeling. At discharge, the variables
      associated with remodeling were: mitral inflow E-wave-to-A-wave velocity ratio
      (E/A), systolic mitral annulus velocity (Sm), early diastolic mitral annulus
      velocity (Em), the mitral inflow E wave to early diastolic mitral annulus
      velocity ratio (E/ Em), left atrial volume (LAV), left ventricular end-systolic
      volume (LVESV), left ventricular end-diastolic volume (LVEDV), and discharge NT
      proBNP level. Only E/Em was an independent predictor of ventricular remodeling
      (odds ratio [OR]=1.143; 95% confidence interval [CI], 1.039-1.258; P=.006). At
      discharge, correlations were observed between the NT-proBNP level and LVEDV,
      LVESV, ejection fraction (EF) and E/Em. At 6 months, correlations with
      ventricular volumes and EF were unchanged, the correlation with E/Em was better
      (r=0.47 vs. r=0.69), and a modest correlation with LAV developed (r=0.43;
      P=.001). CONCLUSIONS: The E/Em ratio was the best echocardiographic predictor of
      left ventricular remodeling after myocardial infarction. The NT-proBNP level had
      no additional predictive value over echocardiography. Correlations between the NT
      proBNP level and ventricular volumes and EF at discharge and 6 months were
      similar, while correlations with E/Em and LAV were better at 6 months.

PMID- 20804698
TI  - Prevalence, clinical characteristics and risk of myocardial infarction in
      patients with cocaine-related chest pain.
AB  - INTRODUCTION AND OBJECTIVES: To investigate the frequency of recent cocaine use
      in patients attending an emergency department for acute chest pain, to describe
      the clinical characteristics of these patients, and to estimate the incidence of
      acute coronary syndrome in this population. METHODS: Observational cohort study
      using a standard questionnaire that includes items on recent cocaine consumption.
      RESULTS: During a 1-year period, 1240 patients aged under 55 years presented with
      chest pain. Of these, 63 (5%) had cocaine-related chest pain (7% of men and 1.8%
      of women). These patients were younger (35+/-10 years vs. 39+/-10 years; P=.002),
      were more frequently male (87% vs. 62%; P< .001), and were more frequently
      smokers (59% vs. 35%; P< .001). Patients who had used cocaine recently had a
      higher incidence of acute myocardial infarction (16 vs. 4%; P< .001), especially
      ST-segment-elevation myocardial infarction (11.1% vs. 1.6%; P< .01). After
      adjusting for coronary risk factors, history of cardiovascular disease and
      previous treatment, the odds ratio for myocardial infarction with recent cocaine
      consumption was 4.3 (95% confidence interval, 2-9.4). CONCLUSIONS: Cocaine
      related chest pain is often encountered in emergency departments, especially in
      men aged under 55 years. It is associated with a four-fold increase in the risk
      of acute myocardial infarction. All male patients aged under 55 years with acute
      chest pain should be asked about cocaine use.

PMID- 20804699
TI  - Effect of acute heart failure following discharge in patients with non-ST
      elevation acute coronary syndrome on the subsequent risk of death or acute
      myocardial infarction.
AB  - INTRODUCTION AND OBJECTIVES: Little is known about how prognosis is influenced by
      readmission for acute heart failure (AHF) following non-ST-segment elevation
      acute coronary syndrome (NSTEACS). The aim of this study was to determine the
      prognostic effect of a first admission for AHF on the risk of acute myocardial
      infarction (AMI) or death in patients who survived an episode of high-risk
      NSTEACS. METHODS: The study involved 972 consecutive patients with high-risk
      NSTEACS who survived after hospital admission. Readmission for AHF was selected
      as the main exposure variable, and its association with subsequent AMI or all
      cause death was assessed using Cox proportional hazards models for time-dependent
      covariates that also included adjustment for competing risks. RESULTS: After a
      median follow-up period of 30 [interquartile range, 12-48] months, 82 patients
      (8.4%) were admitted for AHF, 146 (15%) had an AMI, and 202 (20.8%) died. The
      median time to readmission for AHF was 203 [56-336] days after NSTEACS. Patients
      readmitted for AHF had an increased risk of subsequent death (hazard ratio
      [HR]=1.67; 95% confidence interval [CI], 1.13-2.45; P=.009) or AMI (HR=2.15; 95%
      CI, 1.41-3.27; P< .001), which was independent of baseline prognostic and time
      dependent variables. CONCLUSIONS: Readmission for AHF after high-risk NSTEACS was
      associated with an increased risk of subsequent death or AMI.

PMID- 20804700
TI  - Socioeconomic status and risk of acute myocardial infarction. Population-based
      case-control study.
AB  - INTRODUCTION AND OBJECTIVES: Socioeconomic status is associated with
      cardiovascular mortality. The aims of this study were to investigate the
      association between socioeconomic status and its various indicators and the risk
      of acute myocardial infarction (AMI), and to determine whether any association
      found is independent of the presence of cardiovascular risk factors (CVRFs).
      METHODS: Study cases were matched with controls by age, sex and year of
      recruitment. Cases were recruited from a hospital register and controls from
      cross-sectional studies of the general population. The socioeconomic status was
      determined from educational level and social class, as indicated by occupation.
      Self-reported data were collected on the presence of CVRFs. RESULTS: The study
      included 1369 cases and controls. Both educational level and social class
      influenced AMI risk. Among non-manual workers, there was an inverse linear
      relationship between educational level and AMI risk independent of CVRFs:
      compared with university educated individuals, the odds ratio (OR) for an AMI
      among those with a high school education was 1.63 (95% confidence interval [CI],
      1.16-2.3), and among those with an elementary school education, 3.88 (95% CI,
      2.79-5.39). No association between educational level and AMI risk was observed in
      manual workers. However, the AMI risk was higher in manual workers than non
      manual university educated workers: in those with an elementary school education,
      the increased risk (OR=2.09; 95% CI, 1.59-2.75) was independent of CVRFs.
      CONCLUSIONS: An association was found between socioeconomic status and AMI risk.
      The AMI risk was greatest in individuals with only an elementary school
      education, irrespective of CVRFs and social class, as indicated by occupation.

PMID- 20804701
TI  - Determinants of postoperative atrial fibrillation and associated resource
      utilization in cardiac surgery.
AB  - INTRODUCTION AND OBJECTIVES: Atrial arrhythmias occur after cardiac surgery in 10
      65% of patients. The most common postoperative arrhythmia is atrial fibrillation
      (AF). METHODS: The Tehran Heart Center Cardiovascular Research database (of 15
      580 patients) was used to identify all patients who developed any form of AF as a
      postoperative complication following their first cardiac surgery (e.g. for
      coronary artery bypass grafting [CABG], valve surgery or both), with and without
      cardiopulmonary bypass, between June 2002 and March 2008. RESULTS: Of the 15 580
      patients who underwent a first cardiac surgery, 11 435 (73.4%) were male and
      their mean age was 58.16+/-10.11 years. New-onset AF developed postoperatively in
      1129 (7.2%). New-onset AF occurred most frequently in patients who were aged > or
      =60 years and who had no history of beta-blocker use. In addition, patients were
      more likely to develop new-onset AF if they had valve surgery alone (16.5%) or
      CABG plus valve surgery combined (9.6%), needed intra-aortic balloon
      counterpulsation (IABC), or had a long cardiopulmonary bypass time. Multivariate
      analysis identified the following predictors of postoperative AF: older age,
      history of renal failure, congestive heart disease, operation type, longer
      perfusion time, and use of IABC. The incidence of early readmission (4.4%) was
      significantly higher in patients with postoperative AF, as was the duration of
      hospitalization, both overall and postoperatively. The short-term postoperative
      mortality rate was 3.8%. CONCLUSIONS: Atrial fibrillation frequently develops
      after cardiac surgery and is associated not only with increased morbidity and
      mortality, but also with increased use of health-care resources.

PMID- 20804702
TI  - Apoptosis and acute cellular rejection in human heart transplants.
AB  - INTRODUCTION AND OBJECTIVES: Apoptosis has been implicated in the pathophysiology
      of various forms of heart disease. Acute cellular rejection leads to morbidity
      after heart transplantation and invasive techniques are needed for its diagnosis.
      We investigated the presence of cardiomyocyte apoptosis in transplanted hearts,
      its progression, its relationship with rejection, and the possibility that
      serological markers of apoptosis can be used to detect rejection noninvasively.
      METHODS: Overall, 130 endomyocardial biopsies obtained sequentially from 14
      consecutive patients during the first 6 months following heart transplantation
      underwent histochemical analysis. The degree of acute rejection was determined,
      myocyte apoptosis was assessed using the TUNEL method, and caspase-3 activity was
      measured. In the first 10 patients, soluble Fas, tumor necrosis factor-alpha
      (TNFalpha) and interleukin 6 levels were determined in serum collected at biopsy.
      RESULTS: Apoptotic cells were detected in 81.5% of biopsies. No significant
      correlation was found between the apoptotic index and either the degree of
      rejection or the time from transplantation; there was only a trend to higher
      values during prolonged episodes of rejection, which did not reach statistical
      significance. An inverse correlation was observed between the degree of rejection
      and the TNFalpha level (rs=-0.33; P=.003). There was no correlation with any
      other variable. CONCLUSIONS: Cardiomyocyte loss due to apoptosis was observed in
      transplanted hearts, but no correlation was observed with either acute rejection
      or the time from transplantation. Our findings suggest there could be an inverse
      correlation between rejection and the serum TNFalpha level. No serum parameter
      evaluated was regarded as suitable for the noninvasive diagnosis of acute
      rejection.

PMID- 20804703
TI  - The right heart and pulmonary circulation (IX). The right heart in adults with
      congenital heart disease.
AB  - Right ventricular dysfunction is not uncommon in adults with congenital heart
      disease. In congenital heart disease, unlike acquired heart disease, the right
      ventricle is not always the subpulmonary ventricle: it may support the systemic
      circulation as it does in patients with transposition complexes. The result is
      chronic right ventricular pressure overload. In contrast, pulmonary valve
      regurgitation -a frequent problem after surgical repair of the tetralogy of
      Fallot- imposes a volume overload on the right ventricle. Over time, both
      conditions may lead to right ventricular dysfunction and often this becomes a
      major clinical concern. Clearly, a thorough understanding of right ventricular
      anatomy and physiology is a necessity for those caring for patients with
      congenital heart disease. This article provides an overview of right ventricular
      morphology and the adverse effects of right ventricular dysfunction in adults
      with congenital heart disease.

PMID- 20804704
TI  - Image in cardiology. Infective endocarditis and sudden death.

PMID- 20804705
TI  - Spontaneous coronary dissection and its long-term prognostic implications in a
      cohort of 19 cases.
AB  - Spontaneous coronary artery dissection is a rare cause of acute coronary
      syndrome. It mainly affects women with no significant cardiovascular risk factors
      and its presentation varies from unstable angina to sudden death. Knowledge of
      the condition is based only on individual case reports and the lack of large case
      series means that its treatment and prognostic implications have not been fully
      established. We present data on 19 instances of spontaneous coronary artery
      dissection in 18 patients who were treated at our center between May 1998 and
      January 2009. The median follow-up period was 3.8 years (interquartile range: 1.3
      4.6 years). Once the acute phase had passed, the prognosis was favorable and
      there were no implications for functioning. One patient presented with a relapse
      in another coronary artery and another patient gave birth without complications 3
      years after the dissection.

PMID- 20804706
TI  - Autograft failure during follow-up after the Ross procedure: predictive factors
      in a prospective series.
AB  - To determine the incidence of, and predictive factors for, aortic autograft
      failure during follow-up after the Ross procedure. Of 102 consecutive patients
      who underwent surgery at our centre between 1997 and 2009, we selected 83 (age
      32+/-11 years), all of whom had been discharged without significant autograft
      regurgitation and for whom at least one follow-up echocardiogram was available.
      Autograft failure was defined as the presence of at least moderate regurgitation
      on echocardiography. After a median follow-up period of 4.2 years (range 0.2-10.9
      years), eight patients (9.6%) developed this complication, three of whom required
      valve replacement. The probability of survival without autograft failure at 5
      years was 90% (95% confidence interval [CI] 83%-98%). Multivariate analysis
      showed that undergoing surgery during the first 6 months of the learning curve
      (hazard ratio = 9.1; 95% CI, 1.4-59.4; P=.021) and a large pulmonary annulus
      size, normalized by body surface area, (hazard ratio = 1.4; 95% CI, 1.016-1.924;
      P=.04) were independent predictors of this complication.

PMID- 20804707
TI  - Determining the C-reactive protein level in patients with different clinical
      forms of chagas disease.
AB  - Chagas disease is caused by Trypanosoma cruzi and remains a health problem in the
      developing countries of South America. The condition leads to cardiac conduction
      disturbances and chronic heart failure. In this study, 136 individuals were
      evaluated by the Chagas Disease Study Group of the Hospital de la Universidad
      Estatal de Campinas in Brazil to determine the relationship between chronic heart
      failure and the serum C-reactive protein (CRP) level. When patients were
      stratified according to the different clinical presentations of Chagas disease,
      it was found that the CRP levels in those with severe heart disease and non
      Chagasic cardiopathy were significantly higher than in controls or those with
      mild heart disease (P< .05), even when participants were stratified by age (i.e.
      <40 and > or =40 years). There was a direct linear correlation between age and
      CRP level, such that the older the individual, the higher the CRP level. These
      data provide further evidence for an association between chronic inflammation and
      the development of heart failure. Although CRP elevations are not exclusively
      related to Chagas disease, the CRP level may be a useful marker for the
      progression of Chagas disease to a more advanced phase.

PMID- 20804708
TI  - Mechanical alternans detected by Doppler-derived dP/dt.

PMID- 20804709
TI  - Very late restenosis of a paclitaxel-eluting stent implanted to treat previous in
      stent restenosis of a bare metal stent.

PMID- 20804710
TI  - Sudden cardiac death in a case of undiagnosed pericardial agenesis.

PMID- 20804711
TI  - Aortic stenosis and coronary artery disease in alkaptonuria. Case report.

PMID- 20804712
TI  - Branched stent-graft used for the complete endovascular treatment of a type-II
      thoracoabdominal aortic aneurysm.

PMID- 20804713
TI  - Percutaneous coronary intervention in a patient with a CoreValve aortic valve
      prosthesis.

PMID- 20804715
TI  - Anthropophilic mosquitoes and malaria transmission in the eastern foothills of
      the central highlands of Madagascar.
AB  - Malaria remains a major public health problem in Madagascar, as it is the first
      cause of morbidity in health care facilities. Its transmission remains poorly
      documented. An entomological study was carried out over 1 year (October 2003
      September 2004) in Saharevo, a village located at an altitude of 900m on the
      eastern edge of the Malagasy central highlands. Mosquitoes were sampled weekly
      upon landing on human volunteers and in various resting-places. Out of 5515
      mosquitoes collected on humans, 3219 (58.4%) were anophelines. Eleven anopheline
      species were represented, among which Anopheles funestus, Anopheles gambiae,
      Anopheles arabiensis and Anopheles mascarensis. Out of 677 mosquitoes collected
      in bedrooms by pyrethrum spray catches and in Muirhead-Thomson pits, 656 (96.9%)
      were anopheline belonging to these four latter species. The proportion of
      mosquitoes that fed on human varied according to the resting-places and the
      mosquito species: 86% of An. funestus resting in bedrooms fed on humans, whereas
      only 16% of An. funestus and 0% of An. mascarensis resting in pits fed on humans.
      The proportion of anopheline mosquitoes infected with human Plasmodium was
      measured by circumsporozoite protein-ELISA: 10/633 An. funestus (1.58%), 1/211
      An. gambiae s.l. (0.48%) and 2/268 An. mascarensis (0.75%). The annual
      entomological inoculation rate (number of bites of infected anophelines per
      adult) was estimated at 2.78. The transmission was mainly due to An. funestus and
      only observed in the second half of the rainy season, from February to May. These
      results are discussed in the context of the current malaria vector control policy
      in Madagascar.

PMID- 20804716
TI  - Blood stage Plasmodium falciparum antigens induce T cell independent
      immunoglobulin production via B cell activation factor of the TNF family (BAFF)
      pathway.
AB  - T independent (TI) antigens (Ags) activate monocytes to produce a cytokine,
      termed B cell activation factor (BAFF), involved in immunoglobulin (Ig)
      production. This study aimed to investigate whether the soluble schizont fraction
      of Plasmodium falciparum antigen (sPfAg) and hemozoin (HZ) could act as TI Ag to
      induce P. falciparum (Pf) specific Ig production via BAFF pathway. Co-cultures of
      monocytes and naive B cells from 6 healthy donors were stimulated with sPfAg
      (10mg/ml) or HZ (10MUM). At interval times, the expressions of BAFF on activated
      monocytes, BAFF receptor (BAFF-R) and proliferation nuclear Ag in activated B
      cells were determined by flow cytometry. The soluble BAFF (sBAFF), total and
      specific IgG levels in the supernatants were assessed by enzyme-linked
      immunosorbent assay (ELISA). The finding revealed both sPfAg and HZ could
      activate monocytes to express BAFF on surface and release sBAFF in the
      supernatant within 72h of stimulation. The B cells responded to specific
      activation, indicated by BAFF-R expression on the surface within 72h, marked
      proliferation on day 7, and final production of total and specific IgG during
      days 7-12. Comparing to sPfAg, HZ stimulated monocyte and B cell co-culture to
      express higher levels of BAFF and sBAFF during 24-48h, more BAFF-R on HZ
      activated B cells within 24h and induced marked proliferation of B cells with
      higher Pf specific IgG level. However, stimulation with sPfAg showed a more
      significant correlation between BAFF expression on the activated monocytes at 72h
      and the Pf specific IgG level on day 12 (r=0.961, p=0.039, Pearson Correlation).
      In conclusion, it is possible that both sPfAg and HZ stimulated B cells to
      produce specific IgG with BAFF involvement.

PMID- 20804717
TI  - Characterization of sphingosine-1-phosphate lyase activity by electrospray
      ionization-liquid chromatography/tandem mass spectrometry quantitation of (2E)
      hexadecenal.
AB  - Sphingosine-1-phosphate (S1P) is a sphingolipid signaling molecule crucial for
      cell survival and proliferation. S1P-mediated signaling is largely controlled
      through its biosynthesis and degradation, and S1P lyase (S1PL) is the only known
      enzyme that irreversibly degrades sphingoid base-1-phosphates to
      phosphoethanolamine and the corresponding fatty aldehydes. S1PL-mediated
      degradation of S1P results in the formation of (2E)-hexadecenal, whereas
      hexadecanal is the product of dihydrosphingosine-1-phosphate (DHS1P) degradation.
      Fatty aldehydes can undergo biotransformation to fatty acids and/or alcohols,
      making them elusive and rendering the task of fatty aldehyde quantitation
      challenging. We have developed a simple, highly sensitive, and high-throughput
      protocol for (2E)-hexadecenal quantitation as a semicarbazone derivative by
      liquid chromatography-electrospray ionization-tandem mass spectrometry. The
      approach was applied to determining S1PL activity in vitro with the ability to
      use as low as 0.25MUg of microsomal protein per assay. The method is also
      applicable to the use of total tissue homogenate as the source of S1PL. A
      correction for (2E)-hexadecenal disappearance due to its biotransformation during
      enzymatic reaction is required, especially at higher protein concentrations. The
      method was applied to confirm FTY720 as the inhibitor of S1PL with an IC50 value
      of 52.4MUM.

PMID- 20804718
TI  - Laser capture microdissection for gene expression analysis of inner cell mass and
      trophectoderm from blastocysts.
AB  - Isolation of pure inner cell mass (ICM) and trophectoderm (TE) samples from a
      single blastocyst is necessary to obtain accurate information on the
      transcriptomes of these cells. Laser capture microdissection (LCM) provides the
      possibility to isolate small tissue fractions from heterogeneous tissue sections
      without contamination by the surrounding tissue and without changing the gene
      expression pattern of the cells. However, the small size of blastocysts hampers
      tissue processing prior to LCM. This article describes a protocol for the
      application of LCM to isolate homogeneous ICM and TE cell samples from single
      bovine blastocysts for downstream gene expression analysis.

PMID- 20804719
TI  - Label-free liquid chromatography-tandem mass spectrometry analysis with automated
      phosphopeptide enrichment reveals dynamic human milk protein phosphorylation
      during lactation.
AB  - Protein phosphorylation is a critical posttranslational modification that affects
      cell-cell signaling and protein function. However, quantifying the relative site
      specific changes of phosphorylation occupancies remains a major issue. An online
      enrichment of phosphopeptides using titanium dioxide incorporated in a microchip
      liquid chromatography device was used to analyze trypsin-digested human milk
      proteins with mass spectrometry. The method was validated with standards and used
      to determine the dynamic behavior of protein phosphorylation in human milk from
      the first month of lactation. alpha-Casein, beta-casein, osteopontin, and chordin
      like protein 2 phosphoproteins were shown to vary during this lactation time in
      an independent manner. In addition, changes in specific regions of these
      phosphoproteins were found to vary independently. Novel phosphorylation sites
      were discovered for chordin-like protein 2, alpha-lactalbumin, beta-1,4
      galactosyl transferase, and poly-Ig (immunoglobulin) receptor. Coefficients of
      variation for the quantitation were comparable to those in other contemporary
      approaches using isotopically labeled peptides, with a median value of 11% for
      all phosphopeptide occupancies quantified.

PMID- 20804720
TI  - Site-specific conjugation of metal carbonyl dendrimer to antibody and its use as
      detection reagent in immunoassay.
AB  - We describe here the conjugation of polyclonal goat anti-rabbit antibody to
      generation 4 polyamidoamine (G4-PAMAM) dendrimers carrying (i) (eta(5)
      cyclopentadienyl) iron dicarbonyl succinimidato complexes as infrared (IR)
      probes, (ii) nitroaniline entities as nuclear magnetic resonance (NMR) probes,
      (iii) acetamide groups for surface neutralization, and (iv) hydrazide-terminated
      spacer arms for the reaction with aldehyde. To preserve a high binding affinity,
      the conjugation was performed on the carbohydrate moieties located on the Fc
      fragment. The resulting conjugates were characterized by Fourier transform-IR,
      ultraviolet (UV), and high-mass matrix-assisted laser desorption/ionization time
      of-flight (MALDI-TOF) mass spectrometry. On the basis of relative concentration
      ratios of IR probes and antibody, an average labeling of 30 IR probes per
      antibody was reached (i.e., more than twice the value obtained with our previous
      strategy that generated no spacer arm). Immunoassays revealed that the antibody
      dendrimer conjugates retained 55.1% of immunoreactivity on average with respect
      to underivatized antibody. Finally, the conjugates were used to quantify their
      antigen by solid-phase carbonyl metallo immunoassay (CMIA). Results showed a
      significant enhancement of the IR signal, demonstrating the efficiency of the new
      conjugation strategy and the potential of the new antibody-dendrimer conjugates
      as universal immunoanalytical reagents.

PMID- 20804721
TI  - Nanodiscs allow the use of integral membrane proteins as analytes in surface
      plasmon resonance studies.
AB  - Nanodiscs are small-sized and flat model membranes that provide a close to native
      environment for reconstitution of integral membrane proteins. Incorporation of
      membrane proteins into nanodiscs results in water-soluble proteolipid particles
      making the membrane proteins amenable to a multitude of bioanalytical techniques
      originally developed for soluble proteins. The transmembrane domain of the human
      CD4 receptor was fused to ubiquitin with a preceding N-terminal decahistidine
      tag. The resulting integral membrane protein was incorporated into nanodiscs.
      Binding of the nanodisc-inserted histidine-tagged protein to a monoclonal anti
      pentahistidine antibody was quantified using surface plasmon resonance (SPR)
      experiments. For the first time, a membrane-inserted transmembrane protein was
      employed as analyte while the antibody served as ligand immobilized on the sensor
      chip surface. SPR experiments were conducted in single-cycle mode. We demonstrate
      that the nanodisc-incorporated membrane protein showed nearly identical affinity
      toward the antibody as did the soluble decahistidine-tagged ubiquitin studied in
      a comparative experiment. Advantages of the new experimental setup and potential
      applications are discussed.

PMID- 20804722
TI  - Metabolism of 4-hydroxy-2-nonenal in human polymorphonuclear leukocytes.
AB  - Intracellular metabolism of 4-hydroxy-2-nonenal (HNE), a major product and
      mediator of oxidative stress and inflammation, is analyzed in resting and fMLP
      stimulated human polymorphonuclear leukocytes (PMNL), where this compound is
      generated during activation of the respiratory burst. HNE consumption rate in
      PMNL is very low, if compared to other cell types (rat hepatocytes, rabbit
      fibroblasts), where HNE metabolism is always an important part of secondary
      antioxidative defense mechanisms. More than 98% of HNE metabolites are
      identified. The pattern of HNE intermediates is quite similar in stimulated and
      resting PMNL - except for higher water formation in resting PMNL - while the
      initial velocity of HNE degradation is somewhat higher in resting cells, 0.44
      instead of 0.28 nmol/(min*10(6) cells). The main products of HNE metabolism are 4
      hydroxynonenoic acid (HNA), 1,4-dihydroxynonene (DHN) and the glutathione adducts
      with HNE, HNA, and DHN. Protein-bound HNE and water account for about 3-4% of the
      total HNE derivatives in stimulated cells, while in resting cells protein-bound
      HNE and water are 4% and 20%, respectively. Cysteinyl-glycine-HNE adduct and
      mercapturic acids contribute to about 5%.

PMID- 20804723
TI  - Multi-step oxidations catalyzed by cytochrome P450 enzymes: Processive vs.
      distributive kinetics and the issue of carbonyl oxidation in chemical mechanisms.
AB  - Catalysis of sequential oxidation reactions is not unusual in cytochrome P450
      (P450) reactions, not only in steroid metabolism but also with many xenobiotics.
      One issue is how processive/distributive these reactions are, i.e., how much do
      the "intermediate" products dissociate. Our work with human P450s 2E1, 2A6, and
      19A1 on this subject has revealed a mixture of systems, surprisingly with a more
      distributive mechanism with an endogenous substrate (P450 19A1) than for some
      xenobiotics (P450s 2E1, 2A6). One aspect of this research involves carbonyl
      intermediates, and the choice of catalytic mechanism is linked to the hydration
      state of the aldehyde. The non-enzymatic rates of hydration and dehydration of
      carbonyls are not rapid and whether P450s catalyze the reversible hydration is
      unknown. If carbonyl hydration and dehydration are slow, the mechanism may be set
      by the carbonyl hydration status.

PMID- 20804724
TI  - The Warburg and Crabtree effects: On the origin of cancer cell energy metabolism
      and of yeast glucose repression.
AB  - During the last decades a considerable amount of research has been focused on
      cancer. Recently, tumor cell metabolism has been considered as a possible target
      for cancer therapy. It is widely accepted that tumors display enhanced glycolytic
      activity and impaired oxidative phosphorylation (Warburg effect). Therefore, it
      seems reasonable that disruption of glycolysis might be a promising candidate for
      specific anti-cancer therapy. Nevertheless, the concept of aerobic glycolysis as
      the paradigm of tumor cell metabolism has been challenged, as some tumor cells
      exhibit high rates of oxidative phosphorylation. Mitochondrial physiology in
      cancer cells is linked to the Warburg effect. Besides, its central role in
      apoptosis makes this organelle a promising "dual hit target" to selectively
      eliminate tumor cells. From a metabolic point of view, the fermenting yeast
      Saccharomyces cerevisiae and tumor cells share several features. In this paper we
      will review these common metabolic properties as well as the possible origins of
      the Crabtree and Warburg effects.

PMID- 20804725
TI  - Metabolic management of brain cancer.
AB  - Malignant brain tumors are a significant health problem in children and adults.
      Conventional therapeutic approaches have been largely unsuccessful in providing
      long-term management. As primarily a metabolic disease, malignant brain cancer
      can be managed through changes in metabolic environment. In contrast to normal
      neurons and glia, which readily transition to ketone bodies (beta
      hydroxybutyrate) for energy under reduced glucose, malignant brain tumors are
      strongly dependent on glycolysis for energy. The transition from glucose to
      ketone bodies as a major energy source is an evolutionary conserved adaptation to
      food deprivation that permits the survival of normal cells during extreme shifts
      in nutritional environment. Only those cells with a flexible genome and normal
      mitochondria can effectively transition from one energy state to another.
      Mutations restrict genomic and metabolic flexibility thus making tumor cells more
      vulnerable to energy stress than normal cells. We propose an alternative approach
      to brain cancer management that exploits the metabolic flexibility of normal
      cells at the expense of the genetically defective and metabolically challenged
      tumor cells. This approach to brain cancer management is supported from recent
      studies in mice and humans treated with calorie restriction and the ketogenic
      diet. Issues of implementation and use protocols are presented for the metabolic
      management of brain cancer.

PMID- 20804726
TI  - Monitoring glycolipid transfer protein activity and membrane interaction with the
      surface plasmon resonance technique.
AB  - The glycolipid transfer protein (GLTP) is a protein capable of binding and
      transferring glycolipids. GLTP is cytosolic and it can interact through its FFAT
      like (two phenylalanines in an acidic tract) motif with proteins localized on the
      surface of the endoplasmic reticulum. Previous in vitro work with GLTP has
      focused mainly on the complete transfer reaction of the protein, that is, binding
      and subsequent removal of the glycolipid from the donor membrane, transfer
      through the aqueous environment, and the final release of the glycolipid to an
      acceptor membrane. Using bilayer vesicles and surface plasmon resonance
      spectroscopy, we have now, for the first time, analyzed the binding and lipid
      removal capacity of GLTP with a completely label-free technique. This technique
      is focused on the initial steps in GLTP-mediated transfer and the parameters
      affecting these steps can be more precisely determined. We used the new approach
      for detailed structure-function studies of GLTP by examining the glycolipid
      transfer capacity of specific GLTP tryptophan mutants. Tryptophan 96 is crucial
      for the transfer activity of the protein and tryptophan 142 is an important part
      of the proteins membrane interacting domain. Further, we varied the composition
      of the used lipid vesicles and gained information on the effect of membrane
      properties on GLTP activity. GLTP prefers to interact with more tightly packed
      membranes, although GLTP-mediated transfer is faster from more fluid membranes.
      This technique is very useful for the study of membrane-protein interactions and
      lipid-transfer rates and it can easily be adapted to other membrane-interacting
      proteins.

PMID- 20804728
TI  - MRP4 knockdown enhances migration, suppresses apoptosis, and produces aggregated
      morphology in human retinal vascular endothelial cells.
AB  - The multidrug resistance protein (MRP) MRP4/ABCC4 is an ATP-binding cassette
      transporter that actively effluxes endogenous and xenobiotic substrates out of
      cells. In the rodent retina, Mrp4 mRNA and protein are exclusively expressed in
      vascular endothelial cells, but the angiogenic properties of Mrp4 are poorly
      understood so far. This study aims to explore the angiogenic properties of MRP4
      in human retinal microvascular endothelial cells (HRECs) utilizing the RNA
      interference (RNAi) technique. MRP4 expression was decreased at the mRNA and
      protein levels after stimulation with exogenous vascular endothelial growth
      factor in a dose-dependent manner. RNAi-mediated MRP4 knockdown in HRECs do not
      affect cell proliferation but enhances cell migration. Moreover, cell apoptosis
      induced by serum starvation was less prominent in MRP4 siRNA-treated HRECs as
      compared to control siRNA-treated HRECs. In a Matrigel-based tube-formation
      assay, although MRP4 knockdown did not lead to a significant change in the total
      tube length, MRP4 siRNA-treated HRECs assembled and aggregated into a massive
      tube-like structure, which was not observed in control siRNA-treated HRECs. These
      results suggest that MRP4 is uniquely involved in retinal angiogenesis.

PMID- 20804727
TI  - Transforming acidic coiled-coil protein-3 (Tacc3) acts as a negative regulator of
      Notch signaling through binding to CDC10/Ankyrin repeats.
AB  - We have identified the transforming acidic coiled-coil protein-3 (Tacc3) as a
      binding partner for Notch4/Int3 and were able to show that it binds to the
      intracellular domain (ICD) of all members of the Notch receptor family. Members
      of the Tacc family reside at the centrosomes and associates with microtubules.
      Recent studies suggest that Tacc3 also contributes to the regulation of gene
      transcription. Tacc3 specifically interacts with the Notch4/Int3 CDC10/Ankyrin
      repeats and to a lesser extent, with residues C-terminal to these repeats in the
      ICD. Dual label immunofluorescence of mouse mammary tissue shows Tacc3 co
      localizes with the Notch3 ICD. Co-immunoprecipitation of endogenous Notch and
      Tacc3 proteins from NIH3T3 cell extracts, lung and mammary gland confirms that
      these two proteins interact under physiological conditions. In addition, knock
      down of Tacc3 in NIH3T3 cells leads to the up-regulation of Hey2, a target gene
      for Notch signaling. The affinity of Tacc3 binding to Notch4/Int3 ICD is similar
      to that between Rbpj and Notch4/Int3 ICD. Notch4/Int3 ICD-Tacc3 interaction
      results in the inhibition of transcription from a Hes1-Luciferase reporter vector
      in COS-1 cells. The inhibition was reversed in these cells by increasing the
      levels of Rbpj. Taken together, these results suggest that Tacc3 is a negative
      regulator of the Notch signaling pathway.

PMID- 20804729
TI  - Mitofusin-2 is a novel direct target of p53.
AB  - The tumor suppressor p53 modulates transcription of a number of target genes
      involved in cell cycle arrest, apoptosis, DNA repair, and other important
      cellular responses. Mitofusin-2 (Mfn2) is a novel suppressor of cell
      proliferation that may also exert apoptotic effects via the mitochondrial
      apoptotic pathway. Through bioinformatics analysis, we identified a p53 binding
      site in the Mfn2 promoter. Consistent with this, we showed that the p53 protein
      binds the Mfn2 promoter directly both in vitro and in vivo. Additionally, we
      found that Mfn2 mRNA and protein levels are up-regulated in a p53-dependent
      manner. Furthermore, luciferase assays revealed that the activity of the wild
      type Mfn2 promoter, but not a mutated version of the promoter, was up-regulated
      by p53. These results indicate that Mfn2 is a novel p53-inducible target gene,
      which provides insight into the regulation of Mfn2 and its associated activities
      in the inhibition of cell proliferation, promotion of apoptosis, and modulation
      of tumor suppression.

PMID- 20804730
TI  - Identification and validation of reference genes for expression studies in a rat
      model of neuropathic pain.
AB  - Neuropathic pain is triggered by damage to or as a result of the dysfunction of
      the somatosensory nervous system. Gene expression profiling using DNA microarray
      and real-time PCR have emerged as powerful tools for the elucidation of pain
      specific pathways and identification of candidate biomarkers and therapeutic
      targets. Proper normalization of the gene expression data with stable reference
      genes is a prerequisite to obtaining accurate gene expression changes. We have
      evaluated the stability of six candidate reference genes which include three
      commonly used housekeeping genes (ACTB, GAPDH and HMBS) and three ribosomal
      protein genes (RPL3, RPL19 and RPL29) using real-time PCR in a rat model of
      neuropathic pain. Unexpectedly, ACTB but not GAPDH was stably expressed. In
      addition, we have identified RPL29 and RPL3 as novel reference genes.
      Normalization of expression data using GAPDH or HMBS led to overestimation of
      transcriptional changes. Using RPL29/RPL3/ACTB as reference genes, a number of
      transcripts were found to be specifically and significantly regulated in injured
      dorsal root ganglia. These genes may contribute to the development of neuropathic
      pain pathology and may serve as candidate biomarkers for potential diagnosis.

PMID- 20804731
TI  - A novel GLP-1 analog, BPI3006, with potent DPP IV resistance and good
      glucoregulatory effect.
AB  - Glucagon-like peptide-1 (GLP-1) is an incretin hormone that decreases
      postprandial glycemic excursions by enhancing insulin secretion but with short
      half-life due to rapid inactivation by enzymatic N-terminal truncation.
      Therefore, efforts are being made to improve the stability of GLP-1 via modifying
      its structure or inhibiting dipeptidyl-peptidase IV (DPP IV), which is
      responsible for its degradation. Here we report a novel GLP-1 analog BPI3006 with
      -NHCO- of Ala(8) replaced by -CH(CF(3))NH- and features of its metabolic
      stability, GLP-1 receptor trans-activation and in vivo biological activity.
      BPI3006 is highly resistant to DPP IV-mediated degradation with 91.1% of parental
      peptide left after 24h exposure to the enzyme. BPI3006 also effectively activates
      its target gene promoter through GLP-1 receptor activation by measuring the
      transiently transfected reporter gene green fluorescence protein (GFP) expression
      in NIT-1 cells. Furthermore, BPI3006 could well restrain the glycemia variation
      in fasted normal ICR mice after a single administration followed by an oral
      glucose loading. In spontaneous type 2 diabetic KKA(y) mice, BPI3006 injected
      twice daily could significantly improve the oral glucose tolerance and
      hyperinsulinemia, as well as ameliorate the food and water consumption. In
      conclusion, BPI3006 has enhanced resistance to DPP IV leading to improved
      stability, and shows excellent in vivo biological activity. Thus it may be a new
      candidate for T2DM treatment and its novel modification may provide valuable
      guidance for the future development of long-acting GLP-1 analogs.

PMID- 20804732
TI  - Arginine 469 is a pivotal residue for the Hsc70-GlcNAc-binding property.
AB  - The members of the 70kDa-heat shock proteins (HSP70) family play numerous
      fundamental functions in the cell such as promoting the assembly of multimeric
      complexes or helping the correct folding of nascent proteins to take place. In
      numerous previous studies we demonstrated that Hsp70 and its constitutive isoform
      Hsc70 are endowed of a GlcNAc-binding activity. The molecular modeling of the
      substrate binding domain of Hsc70 and in silico docking experiments using Ser/Thr
      O-GlcNAc motifs allowed to define the potential carbohydrate-recognition region
      and to point out the crucial position of Arg469 as an amino-acid directly
      interacting with the sugar moiety. We cloned a flagged Hsc70 in a pCMV.SPORT6
      vector and we showed that the mutation R469A decreased the GlcNAc-binding
      property of the chaperone of around 70%. This is the first work reporting the
      localization of the GlcNAc-binding domain of a member of the HSP70 family.

PMID- 20804733
TI  - Positioning the expanded akirin gene family of Atlantic salmon within the
      transcriptional networks of myogenesis.
AB  - Vertebrate akirin genes usually form a family with one-to-three members that
      regulate gene expression during the innate immune response, carcinogenesis and
      myogenesis. We recently established that an expanded family of eight akirin genes
      is conserved across salmonid fish. Here, we measured mRNA levels of the akirin
      family of Atlantic salmon (Salmo salar L.) during the differentiation of primary
      myoblasts cultured from fast-skeletal muscle. Using hierarchical clustering and
      correlation, the data was positioned into a network of expression profiles
      including twenty further genes that regulate myogenesis. akirin1(2b) was not
      significantly regulated during the maturation of the cell culture. akirin2(1a)
      and 2(1b), along with IGF-II and several igfbps, were most highly expressed in
      mononuclear cells, then significantly and constitutively downregulated as
      differentiation proceeded and myotubes formed/matured. Conversely, akirin1(1a),
      1(1b), 1(2a), 2(2a) and 2(2b) were expressed at lowest levels when mononuclear
      cells dominated the culture and highest levels when confluent layers of myotubes
      were evident. However, akirin1(2a) and 2(2a) were first upregulated earlier than
      akirin1(1a), 1(1b) and 2(2b), when rates of myoblast proliferation were highest.
      Interestingly, akirin1(1b), 1(2a), 2(2a) and 2(2b) formed part of a module of co
      expressed genes involved in muscle differentiation, including myod1a, myog,
      mef2a, 14-3-3beta and 14-3-3gamma. All akirin paralogues were expressed
      ubiquitously across ten tissues, although mRNA levels were regulated between cell
      types and family members. Gene expression patterns were often highly correlated
      between akirin paralogues, suggesting that natural selection has maintained an
      intricate network of co-regulation among family members. We concluded that the
      Atlantic salmon akirin family performs a multifaceted role during myogenesis and
      has physiological functions spanning many cell-types.

PMID- 20804734
TI  - Zinc-finger protein 91 plays a key role in LIGHT-induced activation of non
      canonical NF-kappaB pathway.
AB  - LIGHT is a member of tumor necrosis factor (TNF) superfamily, and its function is
      mediated through lymphotoxin-beta receptor (LTbetaR), which is known to play
      important roles in inflammatory and immune responses through activation of NF
      kappaB signaling pathways. However, molecular mechanism of LTbetaR ligation
      induced NF-kappaB signaling remains incompletely understood. In this report we
      demonstrate that a novel zinc-finger protein 91 (ZFP91) is a critical regulator
      in LIGHT-induced activation of non-canonical NF-kappaB pathway. ZFP91 appears to
      be required for NF-kappaB2 (p100) processing to p52, nuclear translocation of p52
      and RelB, and DNA-binding activity of NF-kappaB in LIGHT-induced activation of
      non-canonical NF-kappaB pathway. Furthermore, ZFP91 knock-down by RNA
      interference blocks the LIGHT-induced accumulation of NIK and p100 processing, as
      well as the expression of non-canonical NF-kappaB target genes. These data
      clearly indicate that ZFP91 is a key regulator in LIGHT-induced activation of non
      canonical NF-kappaB pathway in LTbetaR signaling.

PMID- 20804735
TI  - Identification of a novel GPR119 agonist, AS1269574, with in vitro and in vivo
      glucose-stimulated insulin secretion.
AB  - The G protein-coupled receptor 119 (GPR119) is highly expressed in pancreatic
      beta-cells. On activation, this receptor enhances the effect of glucose
      stimulated insulin secretion (GSIS) via the elevation of intracellular cAMP
      concentrations. Although GPR119 agonists represent promising oral antidiabetic
      agents for the treatment of type 2 diabetes therapy, they suffer from the
      inability to adequately directly preserve beta-cell function. To identify a new
      structural class of small-molecule GPR119 agonists with both GSIS and the
      potential to preserve beta-cell function, we screened a library of synthetic
      compounds and identified a candidate molecule, AS1269574, with a 2,4,6-tri
      substituted pyrimidine core. Here, we examined the preliminary in vitro and in
      vivo effects of AS1269574 on insulin secretion and glucose tolerance. AS1269574
      had an EC(50) value of 2.5MUM in HEK293 cells transiently expressing human GPR119
      and enhanced insulin secretion in the mouse pancreatic beta-cell line MIN-6 only
      under high-glucose (16.8mM) conditions. This contrasted with the action of the
      sulfonylurea glibenclamide, which also induced insulin secretion under low
      glucose conditions (2.8mM). In in vivo studies, a single administration of
      AS1269574 to normal mice reduced blood glucose levels after oral glucose loading
      based on the observed insulin secretion profiles. Significantly, AS1269574 did
      not affect fed and fasting plasma glucose levels in normal mice. Taken together,
      these results suggest that AS1269574 represents a novel structural class of small
      molecule, orally administrable GPR119 agonists with GSIS and promising potential
      for the treatment of type 2 diabetes.

PMID- 20804736
TI  - Letter to the Editor on "Involvement of AMP-activated-protein-kinase (AMPK) in
      neuronal amyloidogenesis".

PMID- 20804737
TI  - Characterization of caged compounds binding to proteins by NMR spectroscopy.
AB  - Photolysable caged ligands are used to investigate protein function and activity.
      Here, we investigate the binding properties of caged nucleotides and their photo
      released products to well established but evolutionary and structurally unrelated
      nucleotide-binding proteins, rabbit muscle creatine kinase (RMCK) and human
      annexin A6 (hAnxA6), using saturation transfer difference NMR spectroscopy. We
      detect the binding of the caged nucleotides and discuss the general implications
      on interpreting data collected with photolysable caged ligands using different
      techniques. Strategies to avoid non-specific binding of caged compound to certain
      proteins are also suggested.

PMID- 20804738
TI  - Cleavage by MALT1 induces cytosolic release of A20.
AB  - The MALT1 paracaspase has arginine-directed proteolytic activity. A20 is a dual
      ubiquitin-editing enzyme involved in termination of NF-kappaB signaling. Upon T-
      or B-cell receptor engagement human (h) A20 is cleaved by MALT1 after arginine
      439, yielding an N-terminal fragment (hA20p50) and a C-terminal one (hA20p37).
      The hA20p50 fragment has never been detected directly, thus limiting insight into
      the functional consequences of MALT1-mediated cleavage of A20. Here, various
      antibodies were tested, including newly generated hA20p50 and hA20p37 specific
      antibodies, leading to detection of the hA20p50 fragment produced after MALT1
      mediated cleavage of ectopically expressed as well as endogenous A20 proteins.
      The properties of both A20 fragments, generated upon co-expression with a
      constitutively active MALT1 protein, were further studied by sub-cellular
      fractionation and fluorescence microscopy. In contrast to full-length A20 which
      is particulate and insoluble, we found hA20p50 to be soluble and readily released
      into the cytosol whereas hA20p37 was partially soluble, thus suggesting loss of
      compartmentalization as a possible mechanism for MALT1-mediated dampening of A20
      function.

PMID- 20804739
TI  - The identification of a novel Paneth cell-associated antigen in a familial
      adenomatous polyposis mouse model.
AB  - Wnt signaling is important for the differentiation of the Paneth cell lineage in
      the small intestine. However, abnormal Wnt signaling predisposes to intestinal
      tumorigenesis in the familial adenomatous polyposis (FAP) mouse model.
      Vaccination with dendritic cells fused with tumor cells from FAP mice, in which
      Wnt signaling is constitutively activated, induced humoral immunity and
      suppressed intestinal tumor development. We identified the novel antigen Apa1
      (Adenomatous polyposis antigen 1) recognized by antibodies in vaccinated mouse
      serum. Apa1 was localized in the Paneth cell-like tumor cells showing cytoplasmic
      beta-catenin accumulation and also in normal Paneth cells at the bottom of the
      crypts. Phospholipase A2 (Pla2g2a), known to act as an anti-bacterial agent and a
      major suppressor of intestinal tumors, was also expressed in the Paneth cells.
      These results suggest that Apa1 might be involved in anti-microbial defense and
      could influence tumor development in FAP mice via modulation of commensal
      microbiota.

PMID- 20804741
TI  - TNF-alpha induces expression of urokinase-type plasminogen activator and beta
      catenin activation through generation of ROS in human breast epithelial cells.
AB  - Malignant tumors have a capability to degrade the extracellular matrix (ECM) by
      controlled proteolysis. One of the important components of the proteolysis system
      involved in such process is urokinase-type plasminogen activator (uPA). Tumor
      necrosis factor (TNF)-alpha was found to stimulate uPA. TNF-alpha impaired the
      ability of cells to aggregate and to attain compaction. Dyscohesion (cell-cell
      dissociation) induced by TNF-alpha was associated with the disordered expression
      of cadherin/beta-catenin at the sites of cell-cell contact. We observed that
      human breast epithelial (MCF-10A) cells treated with TNF-alpha transiently up
      regulated expression of uPA and its mRNA transcript. In addition, TNF-alpha
      induced activation of beta-catenin in MCF-10A cells. Based on these findings, we
      attempted to examine the role of beta-catenin and its partner, Tcf-4 in
      upregulation of uPA. siRNA knock down of beta-catenin abrogated TNF-alpha-induced
      uPA expression as well as Tcf-4/beta-catenin DNA binding. TNF-alpha-stimulated
      MCF-10A cells exhibited increased intracellular accumulation of reactive oxygen
      species (ROS). TNF-alpha-induced expression of uPA and activation of beta-catenin
      signaling appear to be mediated by ROS in MCF-10A cells, as both events were
      blocked by the antioxidant N-acetylcysteine. Eupatilin (5,7-dihydroxy-3',4',6-tri
      methoxy-flavone), a pharmacologically active flavone derived from Artemisia
      asiatica, has been shown to possess strong antioxidative activity. Eupatilin
      inhibited TNF-alpha-induced intracellular ROS accumulation, expression of uPA and
      beta-catenin activation. Moreover, eupatilin inhibited the TNF-alpha-induced
      invasion of MCF-10A cells. Taken together, the above results suggest that
      eupatilin has chemopreventive effects on mammary tumorigenesis by targeting the
      beta-catenin-uPA axis stimulated by TNF-alpha.

PMID- 20804740
TI  - A novel xenobiotic responsive element regulated by aryl hydrocarbon receptor is
      involved in the induction of BCRP/ABCG2 in LS174T cells.
AB  - Induction of the breast cancer resistance protein (BCRP/ABCG2) expression has
      been found in various tissues and cell-types after exposure to chemicals
      including 17beta-estradiol, rosiglitazone, imatinib, as well as aryl hydrocarbon
      receptor (AhR) activators such as 2,3,7,8-tetrachlorodibenzodioxin, 3
      methylcholanthrene (3MC), and omeprazole. However, the mechanism(s) underlying
      AhR-related induction of ABCG2 is largely unknown. Here, we demonstrate the AhR
      dependent induction of ABCG2 expression in human colon adenocarcinoma LS174T
      cells. Importantly, a novel distal AhR-responsive element (AhRE5) located -2357/
      2333bp upstream of the ABCG2 transcriptional start site has been identified and
      characterized as a functional unit pivotal to 3MC-mediated induction of ABCG2.
      Cell-based reporter assays revealed that deletion of AhRE5 and 4 dramatically
      attenuated 3MC-induced activation of ABCG2 reporter activity, while further
      deletion of the proximal AhRE3 and 2 only moderately changed the luciferase
      activities. Notably, site-directed mutation of the AhRE5 in the BCRP-3.8kb
      reporter construct alone resulted in approximately 80% decrease in 3MC activation
      of the ABCG2 promoter; additional mutation of the AhRE4 site had negligible
      effect on the ABCG2 promoter activity. Moreover, chromatin immunoprecipitation
      assays demonstrated that treatment with 3MC significantly enhanced the
      recruitment of AhR to the AhRE5 occupied region, and mutation of the AhRE5 site
      clearly dissociated AhR protein from this promoter region. Together, these data
      show that the novel distal AhRE5 is critical for AhR-mediated transcriptional
      activation of ABCG2 gene expression in LS174T cells, and it may offer new
      strategies for early identification of ABCG2 inducers, which would be of benefit
      for preventing transporter-associated drug-drug interactions.

PMID- 20804742
TI  - Chronic inhibition of farnesyl pyrophosphate synthase improves endothelial
      function in spontaneously hypertensive rats.
AB  - Farnesyl pyrophosphate synthase (FPPS, EC 2.5.1.10), an essential enzyme in the
      mevalonate pathway, catalyzes the synthesis of isoprenoid intermediates. The
      isoprenoid intermediates are needed for protein isoprenylation of RhoA for its
      function on regulation of endothelial nitric oxide synthase (eNOS). We previously
      reported that FPPS were upregulated in spontaneously hypertensive rats (SHR) when
      compared with Wistar-Kyoto rats (WKY), and this was accompanied by development of
      endothelial dysfunction. Five-week-old male rats were daily gavaged with vehicle
      or an FPPS inhibitor (alendronate, 1 or 10mg/kg). After 12-week administration of
      alendronate, endothelium-dependent and -independent vasorelaxation were measured
      in isolated aortic rings. Twelve-week of alendronate (10mg/kg/day) treatment
      restored the impaired endothelium-dependent vasodilation in SHR. Furthermore,
      long-term treatment with an FPPS inhibitor significantly suppressed RhoA
      activation and increased phospho-eNOS/eNOS ratio. In conclusion, chronic
      treatment with an FPPS inhibitor improves the endothelial function in SHR, and
      the upregulation of phospho-eNOS/eNOS ratio with inhibition of RhoA activation
      may be an important mechanism.

PMID- 20804743
TI  - Pentoxifylline augments TRAIL/Apo2L mediated apoptosis in cutaneous T cell
      lymphoma (HuT-78 and MyLa) by modulating the expression of antiapoptotic proteins
      and death receptors.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) is a
      promising anticancer agent but cutaneous T lymphoma cells (CTCL) are less
      sensitive to TRAIL-induced apoptosis. Here, we report that pentoxifylline (PTX),
      a phosphodiesterase inhibitor, augments TRAIL-mediated apoptosis in HuT-78 and
      MyLa cells through modulating extrinsic death receptors and intrinsic
      mitochondria dependent pathways. Our results clearly show that PTX augments TRAIL
      mediated activation of caspase-8 and induces cleavage of Bid, although PTX alone
      cannot activate caspase-8. This is followed by cytochrome c release and
      subsequent, activation of caspase-9 and caspase-3 and cleavage of poly (ADP
      ribose) polymerase (PARP). Combined treatment downregulates the expression of
      various antiapoptotic proteins including c-FLIP, Bcl-xl, cIAP-1, cIAP-2 and XIAP.
      PTX induces the expression of death receptors DR4 and DR5 on cell surface of both
      the cell types where c-Jun NH2-terminal kinase (JNK) pathway plays an important
      role. Moreover, combined silencing of DR4 and DR5 by small interfering RNA
      abrogates the ability of PTX to induce TRAIL-mediated apoptosis. Thus, this is
      the first demonstration that PTX can potentiate TRAIL-mediated apoptosis through
      downregulation of cell survival gene products and upregulation of death
      receptors.

PMID- 20804744
TI  - Electrophysiological correlates of the masked translation priming effect with
      highly proficient simultaneous bilinguals.
AB  - In the present study, we examined whether there is a symmetrical masked
      translation priming effect for non-cognate words in a group of highly proficient
      (native-like) Basque-Spanish simultaneous bilinguals using event-related brain
      potentials. Participants were presented with a set of Spanish and Basque words
      that could be preceded by their repetitions (an identity condition), their
      translations in the other language, or by two unrelated words (one in each
      language). Results showed a significant masked repetition effect for Spanish as
      well as for Basque targets, mainly evident in the N250 and N400 components.
      Interestingly, a masked translation priming effect was also found in the N400
      component in both language directions (L1-to-L2 and L2-to-L1). Furthermore, the
      magnitude of the N400 modulation for the translation priming effect was similar
      in the two directions. Finally, we also found a language switch cost effect in
      the N250 and N400 components, associated with primes (related and unrelated) that
      did not match the target word's language. This language switch cost effect was
      also highly similar across the two language directions.

PMID- 20804745
TI  - Breath analysis of hydrogen peroxide as a diagnostic tool.
AB  - The potential diagnostic significance of exhaled hydrogen peroxide (H(2)O(2)) in
      pulmonary and systemic disorders has received considerable interest over the last
      few decades. Despite large physiologic variability and low specificity, airway
      H(2)O(2) generation has been found to be consistently increased by inflammatory
      conditions. Furthermore, the level of exhaled H(2)O(2) has been associated with
      efficacy of treatment in various pulmonary diseases. To evaluate this potential
      biomarker, detection methods including standardization protocols have been
      developed. Despite these advances, more comprehensive and controlled studies are
      required. In this manuscript we review progress to date in the analytical
      measurement of exhaled H(2)O(2) and speculate on its potential clinical
      significance as a diagnostic tool.

PMID- 20804746
TI  - Twist1 promotes heart valve cell proliferation and extracellular matrix gene
      expression during development in vivo and is expressed in human diseased aortic
      valves.
AB  - During embryogenesis the heart valves develop from undifferentiated mesenchymal
      endocardial cushions (EC), and activated interstitial cells of adult diseased
      valves share characteristics of embryonic valve progenitors. Twist1, a class II
      basic-helix-loop-helix (bHLH) transcription factor, is expressed during early EC
      development and is down-regulated later during valve remodeling. The requirements
      for Twist1 down-regulation in the remodeling valves and the consequences of
      prolonged Twist1 activity were examined in transgenic mice with persistent
      expression of Twist1 in developing and mature valves. Persistent Twist1
      expression in the remodeling valves leads to increased valve cell proliferation,
      increased expression of Tbx20, and increased extracellular matrix (ECM) gene
      expression, characteristic of early valve progenitors. Among the ECM genes
      predominant in the EC, Col2a1 was identified as a direct transcriptional target
      of Twist1. Increased Twist1 expression also leads to dysregulation of fibrillar
      collagen and periostin expression, as well as enlarged hypercellular valve
      leaflets prior to birth. In human diseased aortic valves, increased Twist1
      expression and cell proliferation are observed adjacent to nodules of
      calcification. Overall, these data implicate Twist1 as a critical regulator of
      valve development and suggest that Twist1 influences ECM production and cell
      proliferation during disease.

PMID- 20804748
TI  - Cancer metabolism: the Warburg effect today.
AB  - One of the first studies on the energy metabolism of a tumour was carried out, in
      1922, in the laboratory of Otto Warburg. He established that cancer cells
      exhibited a specific metabolic pattern, characterized by a shift from respiration
      to fermentation, which has been later named the Warburg effect. Considerable work
      has been done since then, deepening our understanding of the process, with
      consequences for diagnosis and therapy. This review presents facts and
      perspectives on the Warburg effect for the 21st century.

PMID- 20804747
TI  - Polymorphisms of the XRCC3 C722T and the RAD51 G135C genes and the risk of head
      and neck cancer in a Polish population.
AB  - Genetic variations in DNA repair genes may affect an individual's susceptibility
      to head and neck cancer. We performed a case-control study to test the
      association between head and neck cancer risk and two polymorphisms: the C722T of
      the XRCC3 and the G135C of the RAD51-genes of DNA double strand break (DSB)
      repair by homologous recombination (HRR). Genotypes were determined by PCR
      restriction fragment length polymorphism (PCR-RFLP). DNA was isolated from
      peripheral blood lymphocytes of a group of 288 patients consisting of 97 subjects
      with precancerous hyperplastic laryngeal lesions (PHLL) and 191 subjects with
      head and neck squamous cell carcinoma (HNSCC) as well as 353 healthy control
      donors. We found an association between PHLL and the 722CT (OR 6.67; 95% CI 3.02
      14.74) as well as 722TT (OR 4.65; 95% CI 2.30-9.43) variants of the XRCC3 gene.
      Similar relation was observed between these genotypes and HNSCC (OR 2.59; 95% CI
      1.61-4.16 and OR 5.54; 95% CI 3.22-9.52, respectively). Moreover, we also
      observed an association between PHLL (OR 6.04; 95% CI 3.69-9.90) and HNSCC (OR
      6.04; 95% CI 3.69-9.90) and the 135GC variant of the RAD51 gene. The gene-gene
      interaction between XRCC3 and RAD51 polymorphic variants may contribute to higher
      prevalence of PHLL. The increased risk of this disease was observed in case of
      the combination of the 722CT/135GC (OR 3.81; 95% CI 1.55-9.75) as well as the
      722TT/135GC genotypes (OR 5.33; 95% CI 1.96-14.47). The presence of the same
      genes combinations plays a part in higher probability of HNSCC occurrence (OR
      2.42; 95% CI 1.22-4.79 for 722CT/135GC and OR 3.63; 95% CI 1.69-7.76 for
      722TT/135GC). We also found an association between these XRCC3 or RAD51
      polymorphic variants and smoking status in PHLL (ORs 2.85-10.28 and 1.82-7.35,
      respectively) and HNSCC patients (ORs 2.94-13.93 and 1.36-3.94, respectively) as
      well as alcohol intake among PHLL (ORs 3.44-6.12 and 3.52-8.43, respectively) and
      HNSCC subjects (ORs 2.71-7.01 and 2.33-4.62, respectively). In conclusion our
      data showed that the C722T and the G135C polymorphisms of the XRCC3 and the RAD51
      genes might be associated with HNSCC. Finally we suggested that these
      polymorphisms might be used as predictive factor of precancerous lesion for head
      and neck cancer in a Polish population.

PMID- 20804749
TI  - Prostaglandin E2 plays a key role in the immunosuppressive properties of adipose
      and bone marrow tissue-derived mesenchymal stromal cells.
AB  - Mesenchymal stromal cells (MSCs) have important immunosuppressive properties, but
      the mechanisms and soluble factors involved in these effects remain unclear. We
      have studied prostaglandin-E2 (PGE2) as a possible candidate implied in adipose
      tissue-derived MSCs (Ad-MSCs) immunosuppressive properties over dendritic cells
      and T lymphocytes, compared to bone marrow derived MSCs (BM-MSCs). We found that
      both MSCs inhibited the maturation of myeloid-DCs and plasmocytoid-DCs. High
      levels of PGE2 were detected in DCs/MSCs co-cultures. Its blockade with
      indomethacin (IDM) allowed plasmocytoid-DCs but not myeloid-DCs maturation.
      Additionally, high levels of PGE2 were found in co-cultures in which Ad-MSCs or
      BM-MSCs inhibited activated T cells proliferation and pro-inflammatory cytokines
      production. PGE2 blockade by IDM preserved T lymphocytes proliferation but did
      not restore the pro-inflammatory cytokines secretion. However, an increased
      expression of transcription factors and cytokines genes involved in the Th1/Th2
      differentiation pathway was detected in the T cells co-cultured with Ad-MSCs, but
      not with BM-MSCs. In conclusion, we propose that PGE2 is a soluble factor
      mediating most of the immunosuppressive effects of Ad-MSCs and BM-MSCs over p-DCs
      maturation and activated T lymphocytes proliferation and cytokine secretion.

PMID- 20804750
TI  - Isoforms of p38MAPK gamma and delta contribute to differentiation of human AML
      cells induced by 1,25-dihydroxyvitamin D3.
AB  - Inhibition of p38MAPK alpha/beta is known to enhance 1,25-dihydroxyvitamin
      (1,25D)-induced monocytic differentiation, but the detailed mechanism of this
      effect was not clear. We now show that the enhancement of differentiation becomes
      apparent with slow kinetics (12-24 h). Interestingly, the inhibition of p38MAPK
      alpha/beta by their selective inhibitor SB202190 (SB) leads to an upregulated
      expression of p38MAPK isoforms gamma and delta in 1,25D-treated AML cells, in
      cell lines and in primary culture. Although the expression and activating
      phosphorylations of p38MAPK alpha are also increased by an exposure of the cells
      to SB, its kinase activity is blocked by SB, as shown by reduced levels of
      phosphorylated Hsp27, a downstream target of p38MAPK alpha. A positive role of
      p38MAPKs in 1,25D-induced differentiation is shown by the inhibition of
      differentiation by antisense oligonucleotides to all p38MAPK isoforms. Other
      principal branches of MAPK pathways showed early (6 h) activation of MEK/ERK by
      SB, followed by activation of JNK1/2 pathway and enhanced expression and/or
      activation of PU.1, ATF-2 differentiation-related transcription factors. Taken
      together with previous reports, the results indicate that 1,25D-induced
      differentiation is enhanced by the activation of at least three branches of MAPK
      pathways (ERK1/2; p38MAPK gamma/delta; JNK1/2). This activation may result from
      the removal of feedback inhibition of an upstream regulator of those pathways,
      when p38MAPK alpha and beta are inhibited by SB.

PMID- 20804752
TI  - Distribution of goblet cells and MUC5AC mRNA in the canine nictitating membrane.
AB  - This study evaluated the distribution of goblet cells and the expression of
      MUC5AC mRNA in the canine nictitating membrane. The distribution of goblet cells
      in the nictitating membrane and temporal bulbar conjunctiva of beagle dogs was
      examined by histochemical analysis of impression cytology specimens and frozen
      sections. MUC5AC mRNA was detected by the reverse transcription polymerase chain
      reaction (RT-PCR). The distribution of MUC5AC mRNA was also examined by in situ
      hybridization using digoxigenin-labeled antisense and sense RNA probes.
      Histochemical analysis showed that the canine nictitating membrane epithelium
      contained many more periodic acid-Schiff positive goblet cells, particularly on
      the palpebral side, compared with the temporal bulbar conjunctiva. RT-PCR
      revealed that MUC5AC was expressed in both the nictitating membrane and in
      conjunctival tissue. When the distribution of MUC5AC mRNA was assessed by in situ
      hybridization, its expression was high on the palpebral side of the nictitating
      membrane and low in the temporal bulbar conjunctiva. MUC5AC mRNA expression
      corresponded with the distribution of goblet cells by histochemical examination.
      In conclusion, there were numerous goblet cells in the canine nictitating
      membrane epithelium, particularly on the palpebral side, and MUC5AC mRNA was
      expressed in the nictitating membrane epithelium at locations corresponding to
      the goblet cells.

PMID- 20804751
TI  - Trophic factors GDNF and BDNF improve function of retinal sheet transplants.
AB  - The aim of this study was to compare glial-derived neurotrophic factor (GDNF)
      treatment with brain-derived neurotrophic factor (BDNF) treatment of retinal
      transplants on restoration of visual responses in the superior colliculus (SC) of
      the S334ter line 3 rat model of rapid retinal degeneration (RD). RD rats (age 4-6
      weeks) received subretinal transplants of intact sheets of fetal retina
      expressing the marker human placental alkaline phosphatase (hPAP). Experimental
      groups included: (1) untreated retinal sheet transplants, (2) GDNF-treated
      transplants, (3) BDNF-treated transplants, (4) none surgical, age-matched RD
      rats, (5) sham surgery RD controls, (6) progenitor cortex transplant RD controls,
      and (7) normal pigmented rat controls. At 2-8 months after transplantation, multi
      unit visual responses were recorded from the SC using a 40 ms full-field stimulus
      (-5.9 to +1 log cd/m(2)) after overnight dark-adaptation. Responses were analyzed
      for light thresholds, spike counts, response latencies, and location within the
      SC. Transplants were grouped into laminated or rosetted (more disorganized)
      transplants based on histological analysis. Visual stimulation of control RD rats
      evoked no responses. In RD rats with retinal transplants, a small area of the SC
      corresponding to the position of the transplant in the host retina, responded to
      light stimulation between -4.5 and -0.08 log cd/m(2), whereas the light threshold
      of normal rats was at or below -5 log cd/m(2) all over the SC. Overall, responses
      in the SC in rats with laminated transplants had lower response thresholds and
      were distributed over a wider area than rats with rosetted transplants. BDNF
      treatment improved responses (spike counts, light thresholds and responsive
      areas) of rats with laminated transplants whereas GDNF treatment improved
      responses from rats with both laminated and rosetted (more disorganized)
      transplants. In conclusion, treatment of retinal transplants with GDNF and BDNF
      improved the restoration of visual responses in RD rats; and GDNF appears to
      exert greater overall restoration than BDNF.

PMID- 20804753
TI  - Activation of human monocytes by a formyl peptide receptor 2-derived pepducin.
AB  - We synthesized and investigated the effect of formyl peptide receptor 2 (FPR2)
      derived pepducins in human monocytes. The FPR2-based cell-penetrating
      lipopeptide, "pepducin" (F2pal-16), stimulated intracellular calcium increase in
      human monocytes via pertussis toxin (PTX)-sensitive G-protein and phospholipase C
      (PLC) activity. From a functional aspect, we showed that F2pal-16 stimulated
      monocyte chemotaxis. F2pal-16 also stimulated the generation of superoxide anion
      in human monocytes. Moreover, F2pal-16 dramatically increased the production of
      several kinds of pro-inflammatory cytokines (CXCL8, CCL2, IL-1beta and TNF-alpha)
      in human monocytes via NF-kappaB activation. Since FPR2 plays an important role
      in immune responses, F2pal-16 can serve as a useful reagent for the study of FPR2
      mediated immune modulation.

PMID- 20804755
TI  - Identification of ptpro as a novel target gene of Wnt signaling and its potential
      role as a receptor for Wnt.
AB  - Wnt/beta-catenin signaling plays critical roles in embryonic development and
      tissue homeostasis in adults by controlling the expression of target genes. We
      found that expression of ptpro, which encodes a protein tyrosine phosphatase
      receptor type O (PTPRO), was induced by Wnt/beta-catenin signaling in a T cell
      factor/lymphoid enhancer factor dependent manner. Biochemical assays found that
      PTPRO interacted with Wnt via its extracellular domain. In addition, ectopic
      expression of this extracellular domain inhibited Wnt-mediated reporter activity.
      These results suggest that ptpro is a target gene of Wnt/beta-catenin signaling
      and that PTPRO may function as a novel receptor for Wnt.

PMID- 20804754
TI  - Lysophosphatidic acid stimulates gastric cancer cell proliferation via ERK1
      dependent upregulation of sphingosine kinase 1 transcription.
AB  - In MKN1 gastric cancer cells, lysophosphatidic acid (LPA) upregulates expression
      of sphingosine kinase 1 (SphK1) and its downregulation or inhibition suppresses
      LPA mediated proliferation. Although LPA activates numerous signaling pathways
      downstream of its receptors, including extracellular-signal-regulated kinase 1/2,
      p38, JNK, and Akt, and the transactivation of the epidermal growth factor
      receptor, pharmacological and molecular approaches demonstrated that only
      activation of ERK1, in addition to the CCAAT/enhancer-binding protein beta
      transcription factor, is involved in transcriptional upregulation of SphK1 by
      LPA. Our data implicate ERK1 as an important mediator of LPA signaling leading to
      upregulation of SphK1 and point to SphK1 and sphingosine-1-phosphate production
      as potential therapeutic targets in gastric cancer.

PMID- 20804756
TI  - The density of extracellular matrix proteins regulates inflammation and insulin
      signaling in adipocytes.
AB  - Cells can not only sense the type of extracellular matrix (ECM) protein that is
      present in the microenvironment, but they can also sense its density. Here, we
      investigated the effects of ECM protein density on adipokine secretion and
      insulin signaling in adipocytes. To this end, 3T3-L1 adipocytes were cultured on
      the surface of polyacrylamide gels that were coated with gradient densities of a
      collagen type I and fibronectin mixture. We found that high density ECM causes a
      decrease in insulin signaling and adiponectin secretion, whereas the secretion of
      monocyte chemoattractant protein-1 (MCP-1) was increased via the activation of
      nuclear factor-kappaB (NF-kappaB). These results indicate that the density of the
      ECM directly regulates the inflammatory response and insulin sensitivity of
      adipocytes.

PMID- 20804757
TI  - Modulation of interferon signaling by hepatitis C virus non-structural 5A
      protein: implication of genotypic difference in interferon treatment.
AB  - Interferon (IFN) response rate in hepatitis C virus (HCV) patients has been
      varied with genotypes. In this study, we investigated the effects of HCV NS5A
      protein on IFN resistance and compared the genotypic differences of NS5A. We
      showed that IFN-alpha-, poly I:C-, and Sendai virus-induced ISRE transcriptional
      activities were inhibited by both genotype 1b and 2a NS5A protein. We
      demonstrated that not only genotype 1b but also genotype 2a NS5A exerted the
      similar extent of IFN-alpha-induced antiviral activity. We showed that NS5A
      derived from both genotype 1b and 2a showed no significant differential IFN
      responses as seen in HCV patients. These data imply that some other host factor
      may be involved in genotypic differences of IFN antagonism in HCV patients.

PMID- 20804758
TI  - Inverting character of family GH115 alpha-glucuronidases.
AB  - alpha-Glucuronidases of glycoside hydrolase family 115 of the xylose-fermenting
      yeast Pichia stipitis and wood-destroying fungus Schizophyllum commune liberate 4
      O-methyl-D-glucuronic acid residues from aldouronic acids and glucuronoxylan. The
      specific activities of both enzymes depended on polymerization degree of the
      acidic xylooligosaccharides and were inhibited by linear beta-1,4
      xylooligosaccharides. These results suggest interaction of the enzyme with
      several xylopyranosyl residues of the xylan main chain. Using (1)H NMR
      spectroscopy and reduced aldopentaouronic acid (MeGlcA(3)Xyl(4)-ol) as a
      substrate, it was found that both enzymes are inverting glycoside hydrolases
      releasing 4-O-methyl-D-glucuronic acid (MeGlcA) as its beta-anomer.

PMID- 20804759
TI  - Gene encoding the prothoracicotropic hormone of a moth is expressed in the brain
      and gut.
AB  - The molts of lepidopteran insects are typically controlled by the brain-derived
      prothoracicotropic hormone (PTTH) that stimulates ecdysteroidogenesis in the
      prothoracic glands (PGs). We report here that the larvae and pupae of the moth
      Sesamia nonagrioides can molt without brain (PGs must be present), suggesting
      that there might be a secondary source of PTTH. We addressed this issue by
      characterizing spatial and temporal expression patterns of the PTTH gene. To this
      end we identified a major part of the corresponding cDNA. Protein deduced from
      this cDNA fragment consisted of 128 amino acids and showed 48-85% homology with
      the matching regions of PTTHs known from other Lepidoptera. Quantification of
      PTTH expression in major body organs of the last instar larvae revealed high
      expression in the brain (fading in post-feeding larvae) and considerable
      expression in the gut (with a maximum in post-feeding larvae). The content of
      PTTH message in the gut was enhanced after decapitation. It is concluded that the
      molts of S. nonagrioides larvae are driven by PTTH gene expression in the gut.

PMID- 20804760
TI  - Testosterone may increase selective attention to threat in young male macaques.
AB  - Animal studies indicate that sex hormones have widespread effects on the brain,
      cognition and emotion, but findings in humans are inconsistent. Well-controlled
      studies in nonhuman primates are crucial to resolve these discrepancies. In this
      study, we examined the effects of testosterone (T) on emotion in male rhesus
      monkeys. Six young adult males were tested on two emotional tasks during three
      hormonal conditions in a crossover design: when intact at baseline and when
      pharmacologically hypogonadal with add-back of T or placebo. The emotional tasks
      were the Approach-Avoidance task, which tested behavioral responses to three
      categories of objects (familiar, novel, and negative) and a Social Playback task
      which tested behavioral responses to scenes of unfamiliar conspecifics engaged in
      three types of social activities (neutral, positive, or negative). Following a 4
      week baseline period, monkeys were treated with Depot Lupron, 200MUg/kg before
      being randomly assigned to one of two treatment groups: Depot Lupron+Testosterone
      Enanthate (TE, 20mg/kg) or Depot Lupron+oil vehicle. In each treatment group,
      monkeys received one injection of Lupron and one injection of TE or one injection
      of Lupron and one injection of oil at the onset of a 4-week testing period,
      before crossing over to the alternate treatment for an additional 4weeks of
      testing. TE treatment had no effect on behavioral measures in the Approach
      Avoidance task. For the Social Playback task, however, TE significantly increased
      watching time of video clips which depicted fights between unfamiliar
      conspecifics. The enhancing effect of T on watching time for negative social
      scenes is consistent with human data suggesting that T decreases aversion or
      facilitates approach to threatening social stimuli. Further studies are needed to
      understand the mechanisms by which T may mediate responsiveness to social threat
      in male primates.

PMID- 20804761
TI  - An unusual cause of upper gastrointestinal bleeding. Gastric yolk sac tumor with
      a large retroperitoneal metastasis.

PMID- 20804762
TI  - Optimization of biotin labeling of antibodies using mouse IgG and goat anti-mouse
      IgG-conjugated fluorescent beads and their application as capture probes on
      protein chip.
AB  - This study shows the optimization of biotin labeling to antibodies using mouse
      IgG. Several parameters of the biotin labeling, including the molar ratio of
      biotin to antibody, the coupling time and the dialysis time, were studied to
      optimum conditions. The biotin-tagged mouse IgGs were immobilized on avidin
      coated PMMA (Polymethyl Methacrylate) plates via a biotin-avidin linkage. The
      immobilization of the IgG to the chip was quantified using goat anti-mouse IgG
      bound fluorescent beads. It was found that the binding of the fluorescent beads
      saturated when a 10-fold or higher molar ratio of biotin to antibody was used. In
      biotin coupling time tests, sixty minutes was sufficient for the capture probes
      to bind to the surface. However, the results from the dialysis experiments showed
      no difference, indicating that 2 hours was sufficient to remove any unbound
      biotin. Finally, to prove the universality of this protocol using mouse
      antibodies, the optimum conditions were successfully applied in sandwich
      immunoassays designed to detect troponin I (TnI) and N-terminal probrain
      natriuretic peptide (NT-proBNP).

PMID- 20804763
TI  - Pathological and ultrastructural changes in cultured cells induced by venom from
      the ectoparasitic wasp Nasonia vitripennis (Walker) (Hymenoptera: Pteromalidae).
AB  - The ectoparasitic wasp Nasonia vitripennis produces a proteinaceous venom that
      induces death in fly hosts by non-paralytic mechanisms. Previous in vitro assays
      have suggested that the primary cause of cell and tissue death is oncosis, a non
      programmed cell death (PCD) pathway characterized by cellular swelling and lysis.
      However, ultrastructural analyses of BTI-TN-5B1 cells exposed to LC(99) doses of
      wasp venom revealed cellular changes more consistent with apoptosis and/or non
      apoptotic PCD than oncosis or necrosis: By 3h after incubation with venom,
      susceptible cells displayed indentations in the nuclear membranes, large
      nucleoli, and extensive vacuolization throughout the cytoplasm. In the vast
      majority of venom treated cells, annexin V bound to the plasma membrane surface
      within 15 min after treatment, a characteristic consistent with translocation of
      phosphatidylserine to the cell surface during the early stages of apoptosis.
      Likewise, mitochondrial transmembrane potential was depressed in cells within 15
      min in venom-treated cells, an event that occurred in the absence of
      mitochondrial swelling or rupturing of cristae. Active caspase 3 was detected by
      fluorescent labeling in nearly all venom treated cells 3h after exposure to
      venom, and in turn, the potent caspase 3 inhibitor Z-VAD-FMK attenuated the
      morphological changes elicited by wasp venom and afforded protection to BTI-TN
      5B1-4 cells.

PMID- 20804764
TI  - Histopathology and ultrastructure of midgut of Alabama argillacea (Hubner)
      (Lepidoptera: Noctuidae) fed Bt-cotton.
AB  - The interaction of Cry toxins from Bacillus thuringiensis in the midgut of some
      insect larvae determines their efficacies as insecticides, due to the expression
      and availability of sites of action of the toxin in the midgut. Researches point
      out cases of resistance to Cry toxin due to alterations in the binding sites in
      columnar cell membrane. We analyzed the effects of Cry1Ac toxin expressed by Bt
      cotton plants on Alabama argillacea midgut morphophysiology clarifying in levels
      of morphological and ultrastructural. Larvae in the 4th instar of A. argillacea
      after 20 min from ingesting Bt-cotton leaves expressing 0.183 ng of Cry1Ac
      exhibited ultrastructural and morphological modifications in the columnar cells
      with significant changes in the mitochondrial polymorphism, cytoplasmic
      vacuolization, microvillus and basal labyrinth. Expressive morphological
      alterations were also observed in the goblet cells indicating that the columnar
      cells are not the only target of the Cry1Ac toxin. The regenerative cells did not
      modify their structures and exhibited decrease in regeneration capacity. In
      conclusion, the ingestion of 0.183 +/- 0.077 ng of Cry1Ac was enough to promote
      alterations in the columnar and goblet cells, besides reducing significantly the
      number of regenerative cells, which may have contributed to larval death.
      Nevertheless, further studies are necessary to determine the true cause of death.

PMID- 20804765
TI  - Sudden deaths and colony population decline in Greek honey bee colonies.
AB  - During June and July of 2009, sudden deaths, tremulous movements and population
      declines of adult honey bees were reported by the beekeepers in the region of
      Peloponnesus (Mt. Mainalo), Greece. A preliminary study was carried out to
      investigate these unexplained phenomena in this region. In total, 37 bee samples,
      two brood frames containing honey bee brood of various ages, eight sugar samples
      and four sugar patties were collected from the affected colonies. The samples
      were tested for a range of pests, pathogens and pesticides. Symptomatic adult
      honey bees tested positive for Varroa destructor, Nosema ceranae, Chronic bee
      paralysis virus (CBPV), Acute paralysis virus (ABPV), Deformed wing virus (DWV),
      Sacbrood virus (SBV) and Black queen cell virus (BQCV), but negative for Acarapis
      woodi. American Foulbrood was absent from the brood samples. Chemical analysis
      revealed that amitraz, thiametoxan, clothianidin and acetamiprid were all absent
      from symptomatic adult bees, sugar and sugar patty samples. However, some bee
      samples, were contaminated with imidacloprid in concentrations between 14 ng/g
      and 39 ng/g tissue. We present: the infection of Greek honey bees by multiple
      viruses; the presence of N. ceranae in Greek honey bees and the first record of
      imidacloprid (neonicotonoid) residues in Greek honey bee tissues. The presence of
      multiple pathogens and pesticides made it difficult to associate a single
      specific cause to the depopulation phenomena observed in Greece, although we
      believe that viruses and N. ceranae synergistically played the most important
      role. A follow-up in-depth survey across all Greek regions is required to provide
      context to these preliminary findings.

PMID- 20804766
TI  - Probing the transition state of the allosteric pathway of the Shaker Kv channel
      pore by linear free-energy relations.
AB  - Long-range coupling between distant functional elements of proteins may rely on
      allosteric communication trajectories lying along the protein structure, as
      described in the case of the Shaker voltage-activated potassium (Kv) channel
      model allosteric system. Communication between the distant Kv channel activation
      and slow inactivation pore gates was suggested to be mediated by a network of
      local pairwise and higher-order interactions among the functionally unique
      residues that constitute the allosteric trajectory. The mechanism by which
      conformational changes propagate along the Kv channel allosteric trajectory to
      achieve pore opening, however, remains unclear. Such conformational changes may
      propagate in either a concerted or a sequential manner during the reaction
      coordinate of channel opening. Residue-level structural information on the
      transition state of channel gating is required to discriminate between these
      possibilities. Here, we combine patch-clamp electrophysiology recordings of Kv
      channel gating and analysis using linear free-energy relations, focusing on a
      select set of residues spanning the allosteric trajectory of the Kv channel pore.
      We show that all allosteric trajectory residues tested exhibit an open-like
      conformation in the transition state of channel opening, implying that coupling
      interactions occur along the trajectory break in a concerted manner upon moving
      from the closed to the open state. Energetic coupling between the Kv channel
      gates thus occurs in a concerted fashion in both the spatial and the temporal
      dimensions, strengthening the notion that such trajectories correspond to
      pathways of mechanical deformation along which conformational changes propagate.

PMID- 20804767
TI  - Structure of a longitudinal actin dimer assembled by tandem w domains:
      implications for actin filament nucleation.
AB  - Actin filament nucleators initiate polymerization in cells in a regulated manner.
      A common architecture among these molecules consists of tandem WASP homology 2
      domains (W domains) that recruit three to four actin subunits to form a
      polymerization nucleus. We describe a low-resolution crystal structure of an
      actin dimer assembled by tandem W domains, where the first W domain is cross
      linked to Cys374 of the actin subunit bound to it, whereas the last W domain is
      followed by the C-terminal pointed end-capping helix of thymosin beta4. While the
      arrangement of actin subunits in the dimer resembles that of a long-pitch helix
      of the actin filament, important differences are observed. These differences
      result from steric hindrance of the W domain with intersubunit contacts in the
      actin filament. We also determined the structure of the first W domain of Vibrio
      parahaemolyticus VopL cross-linked to actin Cys374 and show it to be nearly
      identical with non-cross-linked W-Actin structures. This result validates the use
      of cross-linking as a tool for the study of actin nucleation complexes, whose
      natural tendency to polymerize interferes with most structural methods. Combined
      with a biochemical analysis of nucleation, the structures may explain why
      nucleators based on tandem W domains with short inter-W linkers have relatively
      weak activity, cannot stay bound to filaments after nucleation, and are unlikely
      to influence filament elongation. The findings may also explain why nucleation
      promoting factors of the Arp2/3 complex, which are related to tandem-W-domain
      nucleators, are ejected from branch junctions after nucleation. We finally show
      that the simple addition of the C-terminal pointed end-capping helix of thymosin
      beta4 to tandem W domains can change their activity from actin filament
      nucleation to monomer sequestration.

PMID- 20804768
TI  - Conformational exchange is critical for the productivity of an oxidative folding
      intermediate with buried free cysteines.
AB  - Much has been learned about the folding of proteins from comparative studies of
      the folding of proteins that are related in sequence and structure. Observation
      of the effects of mutations helps account for sequence-specific properties and
      large variations in folding rates observed in homologous proteins, which are not
      explained by structure-derived descriptions. The folding kinetics of variants of
      a beta-stranded protein, toxin alpha from Naja nigricollis, depends on the length
      of their loop lk1. These proteins, named Tox60, Tox61, and Tox62, contain four
      disulfide bonds. We show that their oxidative refolding pathways are similar.
      Differences in these pathways are restricted to the last step of the reaction,
      that is, the closure of the last disulfide. At this step, two species of three
      disulfide intermediates are observed: intermediate C lacking the B3 disulfide and
      intermediate D lacking the B2 disulfide. Surprisingly, D is the most productive
      intermediate for Tox61 despite the low accessibility of its free cysteines.
      However, in the case of Tox62, its conversion efficiency drops by 2 orders of
      magnitude and C becomes the most productive intermediate. NMR was used in order
      to study the structural dynamics of each of these intermediates. Both three
      disulfide intermediates of Tox61 exist in two forms, exchanging on the 1- to 100
      ms scale. One of these forms is structurally very close to the native Tox61,
      whereas the other is always significantly more flexible on a picosecond-to
      nanosecond timescale. On the other hand, in the case of Tox62, the three
      disulfide intermediates only show a native-like structure. The higher
      conformational heterogeneity of Tox61 intermediate D allows an increased
      accessibility of its free cysteines to oxidative agents, which explains its
      faster native disulfide formation. Thus, residue deletion in loop lk1 probably
      abrogates stabilizing intramolecular interactions, creates conformational
      heterogeneity, and increases the folding rate of Tox60 and Tox61 compared to
      Tox62.

PMID- 20804769
TI  - Effects of turn stability and side-chain hydrophobicity on the folding of beta
      structures.
AB  - Key elements of beta-structure folding include hydrophobic core collapse, turn
      formation, and assembly of backbone hydrogen bonds. In the present folding
      simulations of several beta-hairpins and beta-sheets (peptide 1, protein G B1
      domain peptide, TRPZIP2, TRPZIP4, 20mer, and 20mer(D)P6D), the folding free
      energy landscape as a function of several reaction coordinates corresponding to
      the three key elements indicates apparent dependence on turn stability and side
      chain hydrophobicity, which demonstrates different folding mechanisms of similar
      beta-structures of varied sequences. Turn stability is found to be the key factor
      in determining the formation order of the three structural elements in the
      folding of beta-structures. Moreover, turn stability and side-chain
      hydrophobicity both affect the stability of backbone hydrogen bonds. The three
      stranded beta-sheets fold through a three-state transition in which the formation
      of one hairpin always takes precedence over the other. The different stabilities
      of two anti-parallel hairpins in each three-stranded beta-sheet are shown to
      correlate well with the different levels of their hydrophobic interactions.

PMID- 20804770
TI  - Structural characterization of protein-protein complexes by integrating
      computational docking with small-angle scattering data.
AB  - X-ray crystallography and NMR can provide detailed structural information of
      protein-protein complexes, but technical problems make their application
      challenging in the high-throughput regime. Other methods such as small-angle X
      ray scattering (SAXS) are more promising for large-scale application, but at the
      cost of lower resolution, which is a problem that can be solved by complementing
      SAXS data with theoretical simulations. Here, we propose a novel strategy that
      combines SAXS data and accurate protein-protein docking simulations. The approach
      has been benchmarked on a large pool of known structures with synthetic SAXS
      data, and on three experimental examples. The combined approach (pyDockSAXS)
      provided a significantly better success rate (43% for the top 10 predictions)
      than either of the two methods alone. Further analysis of the influence of
      different docking parameters made it possible to increase the success rates for
      specific cases, and to define guidelines for improving the data-driven protein
      protein docking protocols.

PMID- 20804772
TI  - Simple model of recovery dynamics after mass extinction.
AB  - Biotic recoveries following mass extinctions are characterized by a complex set
      of dynamics, including the rebuilding of whole ecologies from low-diversity
      assemblages of survivors and opportunistic species. Three broad classes of
      diversity dynamics during recovery have been suggested: an immediate linear
      response, a logistic recovery, and a simple positive feedback pattern of species
      interaction. Here we present a simple model of recovery which generates these
      three scenarios via differences in the extent of species interactions, thus
      capturing the dynamical logic of the recovery pattern. The model results indicate
      that the lag time to biotic recovery increases significantly as biotic
      interactions become more important in the recovery process.

PMID- 20804773
TI  - The effect of metapopulation dynamics on the survival and spread of a novel,
      conspicuous prey.
AB  - Animals that deploy chemical defences against predators often signal their
      unprofitability using bright colouration. This pairing of toxicity and
      conspicuous patterning is known as aposematism. Explaining the evolution and
      spread of aposematic traits in previously cryptic species has been the focus of
      much empirical and theoretical work over the last two decades. Existing research
      concerning the initial evolution of aposematism does not however properly
      consider that many aposematic species (such as members of the hymenoptera, the
      lepidoptera, and amphibia) are highly mobile. We argue in this paper that the
      evolution of aposematic displays is therefore often best understood within a
      metapopulation framework; hence in this paper we present the first explicit
      metapopulation model of the evolution of aposematism. Our most general finding is
      that migration tends to reduce the probability that an aposematic prey can
      increase from rarity and spread across a large population. Hence, the best case
      scenarios for the spread of aposematism required fixation of the aposematic form
      in one or more isolated sub-habitats prior to some event which subsequently
      enabled migration. We observed that changes in frequency of new aposematic forms
      within source habitats are likely to be nonmonotonic. First, aposematic prey tend
      to decline in frequency as they migrate outwards from the source habitat to
      neighbouring sink habitats, but subsequently they increase in relative abundance
      in the source, as the descendents of earlier migrants migrate back from newly
      converted sub-populations. This pattern of initial loss and subsequent gain
      between new source and neighbouring sink habitats is then repeated as the
      aposematic form spreads via a moving cline.

PMID- 20804771
TI  - The metalloregulatory zinc site in Streptococcus pneumoniae AdcR, a zinc
      activated MarR family repressor.
AB  - Streptococcus pneumoniae D39 AdcR (adhesin competence repressor) is the first
      metal-sensing member of the MarR (multiple antibiotic resistance repressor)
      family to be characterized. Expression profiling with a DeltaadcR strain grown in
      liquid culture (brain-heart infusion) under microaerobic conditions revealed
      upregulation of 13 genes, including adcR and adcCBA, encoding a high-affinity ABC
      uptake system for zinc, and genes encoding cell-surface zinc-binding pneumococcal
      histidine triad (Pht) proteins and AdcAII (Lmb, laminin binding). The DeltaadcR,
      H108Q and H112Q adcR mutant allelic strains grown in 0.2 mM Zn(II) exhibit a slow
      growth phenotype and an approximately twofold increase in cell-associated Zn(II).
      Apo- and Zn(II)-bound AdcR are homodimers in solution and binding to a 28-mer DNA
      containing an adc operator is strongly stimulated by Zn(II) with K(DNA-Zn)=2.4 *
      10(8) M(-1) (pH 6.0, 0.2 M NaCl, 25  degrees C). AdcR binds two Zn(II) per dimer,
      with stepwise Zn(II) affinities K(Zn1) and K(Zn2) of >=10(9) M(-1) at pH 6.0 and
      >=10(12) M(-1) at pH 8.0, and one to three lower affinity Zn(II) depending on the
      pH. X-ray absorption spectroscopy of the high-affinity site reveals a
      pentacoordinate N/O complex and no cysteine coordination, the latter finding
      corroborated by wild type-like functional properties of C30A AdcR. Alanine
      substitution of conserved residues His42 in the DNA-binding domain, and His108
      and His112 in the C-terminal regulatory domain, abolish high-affinity Zn(II)
      binding and greatly reduce Zn(II)-activated binding to DNA. NMR studies reveal
      that these mutants adopt the same folded conformation as dimeric wild type apo
      AdcR, but fail to conformationally switch upon Zn(II) binding. These studies
      implicate His42, His108 and H112 as metalloregulatory zinc ligands in S.
      pneumoniae AdcR.

PMID- 20804774
TI  - Post-stroke pharmacological intervention: promoting brain recovery from injury in
      the future.

PMID- 20804776
TI  - Tetrahydroberberine blocks ATP-sensitive potassium channels in dopamine neurons
      acutely-dissociated from rat substantia nigra pars compacta.
AB  - Tetrahydroberberine (THB) exhibits neuroprotective effects but its targets and
      underlying mechanisms are largely unknown. Emerging evidence indicates that ATP
      sensitive potassium (K(ATP)) channels in the substantia nigra pars compacta (SNc)
      promote Parkinson disease (PD) pathogenesis, thus blocking K(ATP) channels may
      protect neurons against neuronal degeneration. In the present study, we tested a
      hypothesis that THB blocks K(ATP) channels in dopaminergic (DA) neurons acutely
      dissociated from rat SNc. Using perforated patch-clamp recording in current-clamp
      mode, the functional K(ATP) channels can be opened by persistent perfusion of
      rotenone, an inhibitor of complex I of the mitochondrial respiratory chain. Bath
      application of THB reversibly blocks opened K(ATP) channels in a concentration
      dependent manner, which is comparable to a classical K(ATP) channel blocker, Tol.
      Compared to THB analogs, l-stepholidine (l-SPD) or l-tetrahydropalmatine (l-THP),
      THB exhibits more profound blockade in K(ATP) channels. In addition, exposure of
      THB alone to the recorded neuron increases action potential firing, and THB also
      restores rotenone-induced membrane hyperpolarization in the presence of dopamine
      D2 receptor antagonist (sulpiride), suggesting that THB exhibits an excitatory
      effect on SNc DA neurons through the block of K(ATP) channels. Collectively, the
      blockade of neuronal K(ATP) channels by THB in SNc DA neurons is a novel
      pharmacological mechanism of THB, which may contribute to its neuroprotective
      effects in PD.

PMID- 20804775
TI  - Disease-modifying activity of progesterone in the hippocampus kindling model of
      epileptogenesis.
AB  - Progesterone (P) is an endogenous anticonvulsant hormone. P is being evaluated as
      a treatment for epilepsy, traumatic brain injury, and other complex neurological
      conditions. Preclinical and clinical studies suggest that P appears to interrupt
      epileptogenic events. However, the potential disease-modifying effect of P in
      epileptogenic models is not widely investigated. In this study, we examined the
      effects of P on the development of hippocampus kindling in female mice. In
      addition, we determined the role of progesterone receptors (PR) in the P's effect
      on the kindling epileptogenesis utilizing PR knockout (PRKO) mice. P, at 25
      mg/kg, did not affect seizures and did not exert sedative/motor effects in fully
      kindled mice. P treatment (25 mg/kg, twice daily for 2 weeks) significantly
      suppressed the rate of development of behavioral kindled seizure activity evoked
      by daily hippocampus stimulation in wild-type (WT) mice, indicating a disease
      modifying effect of P on limbic epileptogenesis. There was a significant increase
      in the rate of 'rebound or withdrawal' kindling during drug-free stimulation
      sessions following abrupt discontinuation of P treatment. A washout period after
      termination of P treatment prevented such acceleration in kindling. PRKO mice
      were kindled significantly slower than WT mice, indicating a modulatory role of
      PRs in seizure susceptibility. P's effects on early kindling progression was
      partially decreased in PRKO mice, but the overall (~2-fold) delay in the rate of
      kindling for the induction of stage 5 seizures was unchanged in PRKO mice.
      Moreover, the acute anticonvulsant effect of P was undiminished in fully-kindled
      PRKO mice. These studies suggest that P exerts disease-modifying effects in the
      hippocampus kindling model at doses that do not significantly affect seizure
      expression and motor performance, and the kindling-retarding effects of P may
      occur partly through a complex PR-dependent and PR-independent mechanism.

PMID- 20804777
TI  - Copulation modifies AR and ERalpha mRNA expression in the male rat brain.
AB  - BACKGROUND/AIMS: One day after male sexual behavior [one ejaculation or
      copulation to satiety (ad libitum copulation during 4h with the same female)]
      androgen receptor immunoreactivity (AR-ir) is decreased and estrogen receptor
      alpha immunoreactivity (ERalpha-ir) increased in various brain areas related with
      its control. Seven days after sexual satiety there was a limited recovery of
      sexual behavior accompanied by a partial recuperation in the AR-ir. In this study
      we evaluated if these changes in AR-ir and ERalpha-ir were paralleled by
      variations in their respective mRNA. METHODS: Sexually experienced male rats were
      sacrificed at different intervals: immediately, 24h or seven days after sexual
      satiety or 24h after one ejaculation. The changes in AR and ERalpha mRNA were
      analyzed by in situ hybridization using digoxigenine-labeled oligonucleotide
      probes in the MPOA, LSV and the bed nucleus of the stria terminalis, medial
      division, anterior (BSTMA). RESULTS: AR mRNA density was decreased in the MPOA
      and the LSV immediately and 24h after one ejaculation or sexual satiety. Seven
      days after copulating to satiety, there was a recovery of AR mRNA. In the BSTMA
      the different behavioral conditions did not modify the AR mRNA expression. In the
      MPOA, LSV and BSTMA the ERalpha mRNA increased after a single ejaculation and at
      all intervals after sexual satiety. CONCLUSION: In some brain areas and after
      some intervals of sexual activity, the changes in steroid protein receptors
      expression seem to be consequence of parallel changes in the expression of the
      respective mRNA.

PMID- 20804779
TI  - IV nicotine self-administration in rats using the consummatory operant licking
      response.
AB  - Nicotine self-administered by tobacco smoking or chewing is very addictive in
      humans. Rat models have been developed in which nicotine is self-administered IV
      by the rats pressing a lever. However the reinforcing value of nicotine is much
      less in these models than the addictiveness of human tobacco use would indicate.
      The IV nicotine self-administration operant lever press model does not fully
      capture important aspects of tobacco use in humans. Conditioned oral consumption
      actions of smoking or chewing tobacco may play important roles in tobacco
      addiction. Neural circuitry underlying essential food consummatory responses may
      facilitate consummatory aspects of tobacco intake. To capture this motor
      consummatory aspect of tobacco addiction in the rat model of nicotine self
      administration, we have developed a method of using a licking response instead of
      a lever press to self-administer IV nicotine. Sprague-Dawley rats were trained to
      lick one of two waterspouts for IV nicotine (0.03mg/kg/infusion). With the
      licking response rats self-administered stable nicotine levels throughout 24
      sessions (45min each) of testing. The number of total licks/session significantly
      increased in a linear fashion over that period. The number of licks/infusion was
      substantial, rising steadily with training to an average of over 100
      licks/infusion. Including the consummatory motor act with nicotine self
      administration could help better model the compulsive aspects of tobacco
      addiction in humans.

PMID- 20804780
TI  - Toxicometabolomics approach to urinary biomarkers for mercuric chloride (HgCl2)
      induced nephrotoxicity using proton nuclear magnetic resonance (1H NMR) in rats.
AB  - The primary objective of this study was to determine and characterize surrogate
      biomarkers that can predict nephrotoxicity induced by mercuric chloride (HgCl2)
      using urinary proton nuclear magnetic resonance (1H NMR) spectral data. A
      procedure for (1)H NMR urinalysis using pattern recognition was proposed to
      evaluate nephrotoxicity induced by HgCl2 in Sprague-Dawley rats. HgCl2 at 0.1 or
      0.75 mg/kg was administered intraperitoneally (i.p.), and urine was collected
      every 24 h for 6 days. Animals (n=6 per group) were sacrificed 3 or 6 days post
      dosing in order to perform clinical blood chemistry tests and histopathologic
      examinations. Urinary 1H NMR spectroscopy revealed apparent differential
      clustering between the control and HgCl2 treatment groups as evidenced by
      principal component analysis (PCA) and partial least square (PLS)-discriminant
      analysis (DA). Time- and dose-dependent separation of HgCl2-treated animals from
      controls was observed by PCA of 1H NMR spectral data. In HgCl2-treated rats, the
      concentrations of endogenous urinary metabolites of glucose, acetate, alanine,
      lactate, succinate, and ethanol were significantly increased, whereas the
      concentrations of 2-oxoglutarate, allantoin, citrate, formate, taurine, and
      hippurate were significantly decreased. These endogenous metabolites were
      selected as putative biomarkers for HgCl2-induced nephrotoxicity. A dose response
      was observed in concentrations of lactate, acetate, succinate, and ethanol, where
      severe disruption of the concentrations of 2-oxoglutarate, citrate, formate,
      glucose, and taurine was observed at the higher dose (0.75 mg/kg) of HgCl2.
      Correlation of urinary (1)H NMR PLS-DA data with renal histopathologic changes
      suggests that 1H NMR urinalysis can be used to predict or screen for HgCl2
      induced nephrotoxicity.

PMID- 20804781
TI  - Formulation and characterization of silk sericin-PVA scaffold crosslinked with
      genipin.
AB  - A porous-three-dimensional scaffold shows several advantages in terms of tissue
      engineering since it can provide a framework for cells to attach, proliferate and
      form an extracellular matrix. Sericin, a by-product from the silk industry, can
      form a three-dimensional scaffold with PVA after freeze-drying but has a fragile
      structure. Glycerin (as a plasticizer) and genipin (a crosslinking agent) are
      necessary to make a strong and stable matrix. Our objective was to investigate
      the properties of a three-dimensional silk sericin and PVA scaffold with and
      without glycerin and genipin at various concentrations. SEM showed that adding
      glycerin into scaffold gave better uniformity and porosity. Smaller pore sizes
      and better uniformity were found as the concentration of genipin in the scaffold
      increased. The results of FTIR indicated that glycerin retained a high moisture
      content and had a major effect at 3286 cm(-1), indicating the presence of water
      molecule in the matrix structure. Adding genipin into the scaffold resulted in a
      higher degree of crosslinking or fewer free ?-amino groups, as shown by the
      decrease in the stretching (=C-H) peak and absorption peaks around 1370-1650 cm(
      1), respectively. The sericin/PVA scaffold had a low water sorption capacity, but
      adding glycerin significantly increased this property. Genipin further enhanced
      the moisture absorption capacity of the scaffold and extended the time taken to
      reach equilibrium. After immersing the sericin/PVA scaffold into purified water,
      the scaffold completely dissolved within an hour, whereas the scaffolds
      containing glycerin or glycerin with 0.1% genipin swelled 8 and 11 times,
      respectively, compared with the initial stage after 6h of immersion. In terms of
      mechanical properties, the sericin/PVA/glycerin scaffold exhibited a similar
      compressive strength to the scaffold with a high genipin concentration, whereas a
      low concentration of genipin softened and reduced the compressive strength of the
      scaffold. A small amount of sericin was released from the scaffold and a higher
      concentration of genipin, resulting in less protein leaching compared to non
      crosslinked sericin/PVA. The fraction of protein released from the
      sericin/PVA/glycerin scaffold was about 4%, with values of about 1 and 0.04% in
      the case of scaffolds with 0.01 and 0.1% genipin, respectively. All results
      indicated that the composition of the scaffolds had a significant effect on their
      physical properties, and that can easily be tuned to obtain scaffolds suitable
      for biological applications.

PMID- 20804778
TI  - Novelty-evoked activity in open field predicts susceptibility to helpless
      behavior.
AB  - Learned helplessness in animals has been used to model disorders such as
      depression and post-traumatic stress disorder (PTSD), but there is a lack of
      knowledge concerning which individual behavioral characteristics at baseline can
      predict helpless behavior after exposure to inescapable stress. The first aim of
      this study was to determine behavioral predictors of helplessness using the novel
      and familiar open-field tests, sucrose consumption, and passive harm-avoidance
      tasks before learned helplessness training and testing. Individual differences in
      physiologic responses to restraint stress were also assessed. A cluster analysis
      of escape latencies from helplessness testing supported the division of the
      sample population of Holtzman rats into approximately 50% helpless and 50% non
      helpless. Linear regression analyses further revealed that increased reactivity
      to the novel environment, but not general activity or habituation, predicted
      susceptibility to learned helplessness. During restraint stress there were no
      mean differences in heart rate, heart rate variability, and plasma corticosterone
      between helpless and non-helpless rats; however, a lower heart rate during stress
      was associated with higher activity levels during exploration. Our most important
      finding was that by using an innocuous screening tool such as the novel and
      familiar open-field tests, it was possible to identify subjects that were
      susceptible to learned helplessness.

PMID- 20804782
TI  - Immunostimulatory activity of the polysaccharides from Hyriopsis cumingii.
AB  - The immunostimulatory activity of Hyriopsis cumingii polysaccharides (HCPS) was
      evaluated by using in vitro cell models and in vivo animal models. The results
      demonstrated that crude HCPS and its purified fractions (HCPS-1, HCPS-2 and HCPS
      3) could promote the splenocyte proliferation, increase the activity of acid
      phosphatase in peritoneal macrophages and strengthen peritoneal macrophages to
      devour neutral red in vitro in a dose-dependent manner. Furthermore, HCPS-3
      exhibited much stronger immunostimulatory activity in vitro than crude HCPS, HCPS
      1 and HCPS-2, probably due to the higher sulfate content of HCPS-3. For assay in
      vivo, crude HCPS significantly increased the indices of spleen and thymus, the
      activity of lysozyme in serum and the swelling rate of earlap in delayed-type
      hypersensitivity in a dose-dependent manner. These results suggested that HCPS
      might be a potential natural immunomodulator.

PMID- 20804783
TI  - A macrophage migration inhibitory factor like gene from scallop Chlamys farreri:
      Involvement in immune response and wound healing.
AB  - Macrophage migration inhibitory factor (MIF) is an evolutionarily ancient and
      highly conserved cytokine with multiple functions. In the present study, a MIF
      like gene was cloned from Zhikong scallop Chlamys farreri (designated as CfMIF)
      based on expressed sequence tag (EST) analysis and rapid amplification of cDNA
      ends (RACE) approach. The full-length cDNA of CfMIF was of 2296bp, consisting of
      a 5' untranslated region (UTR) of 60bp, a 3' UTR of 1903bp with a poly(A) tail
      and an open reading frame (ORF) of 333bp encoded 111 amino acid residues with a
      calculated molecular mass of 12.6kDa and a theoretical isoelectric point of 5.63.
      The deduced amino acid sequence of CfMIF shared 27-50.5% similarity with those of
      other known MIFs. A conserved MIF domain was identified in the deduced amino acid
      sequence of CfMIF, and conserved proline(2) and lysine(33) were also found to be
      present in CfMIF. Phylogenetic analysis revealed that CfMIF is one of MIF
      members. The tissue distribution and temporal expression of CfMIF in hemocytes of
      scallop after lipopolysaccharide (LPS), peptidoglycan (PGN) and beta-glucan
      stimulation were detected by real-time RT-PCR. CfMIF gene was ubiquitously
      expressed in six selected tissues of healthy scallops, with the higher expression
      levels in hepatopancreas, mantle and gill. In comparison with the control group,
      the expression of CfMIF mRNA in hemocytes was up-regulated significantly at 6h,
      24h and 48h after LPS treatment, and at all time points after PGN and glucan
      treatment. The cDNA fragment encoding mature peptide of CfMIF was recombined and
      expressed in Escherichia coli BL21 (DE3) pLysS. The recombinant protein of CfMIF
      (rCfMIF) promoted sheep fibroblast migration into scraped spaces in vitro. These
      results generated from the present study encourage us to suggest that CfMIF was a
      novel member of MIF family, and it was involved in immune response and wound
      healing by promoting fibroblast migration.

PMID- 20804784
TI  - Does early life toluene exposure alter the expression of NMDA receptor subunits
      and signal transduction pathway in infant mouse hippocampus?
AB  - We aim to investigate the critical window of susceptibility to toluene exposure
      during brain development and the effects of fetal and neonatal toluene exposure
      on the expression of N-methyl-d-aspartate (NMDA) receptor subunits and related
      transduction pathway in infant mice hippocampus. Pregnant mice (GD 14), male
      offspring (postnatal day; PND 2) or PND 8 were exposed to either a filtered air
      control (0ppm), or 5, or 50ppm of toluene for 6h per day for 5 consecutive days.
      On PND 21, the expression levels of NMDA receptor subunits, cyclic AMP responsive
      element binding protein (CREB)-1, calcium/calmodulin-dependent protein kinase
      (CaMK)-IV, and apoptotic related genes (Bax, Bcl) mRNAs in the hippocampus were
      estimated using quantitative real-time RT-PCR and immunohistochemical analyses.
      NR2B, CaMKIV and CREB1 mRNAs increased significantly in the hippocampus of mice
      exposed to 50ppm toluene on PND 2-6. In contrast, almost all memory function
      related gene mRNAs and proapoptotic and anti-apoptotic ratio increased
      significantly in mice exposed to 5 or 50ppm toluene on PND 8-12. However, mice
      exposed to toluene on GD 14-18 showed no significant change. Increased active
      caspase-3 immunoreactive cells were found in hippocampal CA1 area of PND 21 male
      mice exposed to 5ppm toluene during PND 8-12. Our results suggest that late
      postnatal period may be a vulnerable and critical period to toluene exposure.
      Then, we have also examined the effect of toluene exposure in brain development
      on learning ability in young adult mice and found that poor spatial learning
      performance in PND 49 male mice exposed to 5ppm toluene during critical period.
      This is the first study to show that the early toluene exposure induces
      persistent of the alteration of memory function-related genes in infant mice and
      memory deficit in later life via modulating the synaptic morphology and function.

PMID- 20804786
TI  - Detection of rotavirus A in sewage samples using multiplex qPCR and an evaluation
      of the ultracentrifugation and adsorption-elution methods for virus
      concentration.
AB  - Group A rotaviruses (RV-A) are the most common agents of viral gastroenteritis in
      children worldwide. The goal of this study was to compare two different methods
      to concentrate RV-A from sewage samples and to improve the detection and
      quantification of RV-A using a multiplex quantitative PCR assay with an internal
      control. Both RV-A and the internal control virus, bacteriophage PP7, were seeded
      into wastewater and then concentrated using either an ultrafiltration-based
      adsorption-elution protocol or an ultracentrifugation-based protocol. Real time
      multiplex quantitative PCR was used to quantify the purified RV-A and PP7, and
      the results of the multiplex assay were compared with the results of the monoplex
      assays. The ultracentrifugation-based method had a mean recovery rate of 47%
      (range: 34-60%), while the ultrafiltration-based adsorption-elution method had a
      mean recovery rate of 3.5% (range: 1.5-5.5%). These results demonstrate that
      ultracentrifugation is a more appropriate method for recovering RV-A from
      wastewater. This method together with the multiplex qPCR assay may be suitable
      for routine laboratory use.

PMID- 20804785
TI  - Phosducin and monomeric beta-actin have common epitope recognized by anti
      phosducin antibodies.
AB  - Phosducin family proteins are regulators of cytoplasmic processes. The main
      function ascribed to phosducin is the binding and sequestration of the beta
      subunit of heterotrimeric G proteins. Phosducin-like protein 1, longer than
      phosducin by 37 amino-acids, is involved in chaperoning of newly synthesized
      proteins. beta-Actin, a component of the cytoskeleton, participates in cell
      movement. There is no apparent evolutionary relationship between phosducin and
      beta-actin nor structure similarity. Nevertheless we obtained the polyclonal
      antibodies named ap33, originally directed against a phosducin-derived peptide
      (SQSLEEDFEGQATHTGPK), that also recognized beta-actin. The epitope on the beta
      actin molecule was characterized. It is a conformational epitope grouping some of
      the L-D-F-E-Q-A-T-K amino-acids found in the peptide originally used to obtain
      the antibodies. The main part of the epitope is localized on the actin-actin
      interface of polymerized actin, so it is accessible only on monomeric actin. The
      existence of a common epitope on the molecules of phosducin and beta-actin may
      reflect a topological similarity of a small region of their surfaces.

PMID- 20804787
TI  - A one-step reverse transcription real-time PCR assay for the detection and
      quantitation of Grapevine fanleaf virus.
AB  - A TaqMan((r)) one-step reverse transcription real-time PCR (RT-qPCR) assay was
      developed for the specific detection and relative quantitation of Grapevine
      fanleaf virus (GFLV), the causal agent of grapevine fanleaf degeneration disease.
      The assay was targeted to a conservative region located in the 2A(HP) gene of the
      GFLV RNA2 molecule. The assay specificity was evaluated on GFLV isolates from a
      wide range of geographical regions and on other viruses infecting grapevines. The
      sensitivity of the developed assay for GFLV detection was approximately 1000-fold
      higher than the sensitivity of the conventional ELISA. Concentrations as low as
      10 genome copies of GFLV per reaction were reliably detected using RT-qPCR. The
      new method offers a fast, reliable, specific and sensitive identification test
      for GFLV that is easily applicable for high-throughput diagnosis of GFLV in
      different types of grapevine material, including dormant phloem scrapings. The
      quantitative nature of the assay was evaluated by monitoring the seasonal
      variation of the amount of GFLV present in the plant phloem.

PMID- 20804788
TI  - Administration of GABA(B) receptor positive allosteric modulators inhibit the
      expression of previously established methamphetamine-induced conditioned place
      preference.
AB  - Little is known about the role of GABA(B) receptors (GABA(B)Rs) in the
      maintenance of memories associated with using abused substances. We have embarked
      on a series of studies designed to determine if enhancing the efficacy of GABA
      occupied GABA(B)Rs with positive allosteric modulators (PAMs) can negate
      previously established conditioned place preference (CPP) induced by
      methamphetamine. In the current study, we evaluated the effects of acute
      administration of GABA(B)R PAMs, GS39783 and CGP7930. We determined that post
      conditioning treatments with these PAMs, administered in the home cage, blocked
      the subsequent expression of methamphetamine-induced CPP. These data indicate
      that selectively augmenting GABA-occupied GABA(B)R signaling is sufficient to
      reduce memory maintenance and/or the salience of contextual cues previously
      associated with methamphetamine.

PMID- 20804789
TI  - Age and gene overexpression interact to abolish nesting behavior in Tg2576
      amyloid precursor protein (APP) mice.
AB  - Elucidating the modulators of social behavioral is important in understanding the
      neural basis of behavior and in developing methods to enhance behavior in cases
      of disorder. The work here stems from the observation that the Alzheimer's
      disease mouse model Tg2576, overexpressing human mutations of the amyloid-beta
      precursor protein (APP), fails to construct nests when supplied paper towels in
      their home cages. Experiments using commercially available cotton nesting
      material found similar results. Additional experiments revealed that the genotype
      effect is progressively modulated by age in APP mice but not their WT
      counterparts. There was no effect of sex on nesting behavior in any group.
      Finally, this effect was independent of ambient temperature - even when subjected
      to a cold environment, APP mice fail to build nests whereas WT mice do. These
      results suggest that the APP gene plays a role in affiliative behaviors and are
      discussed in relation to disorders characteristic of mutations in the APP gene
      and in affective dysfunction, including Alzheimer's disease.

PMID- 20804790
TI  - Opposite effects on the ingestion of ethanol and sucrose solutions after
      injections of muscimol into the nucleus accumbens shell.
AB  - Injection of the GABA(A) receptor agonist muscimol into the nucleus accumbens
      shell (AcbSh) elicits robust feeding in satiated rats, but has no effect on water
      intake. The current study was designed to examine whether intra-AcbSh muscimol
      injections influence the intake of ethanol solutions in rats trained to drink
      using a limited access paradigm. We confirmed that bilateral injections of
      muscimol (100 ng) into the AcbSh produce large increases in the intake of sucrose
      solutions and of the chow maintenance diet but found in two independent
      experiments that these injections potently reduce the intake of a 10% ethanol
      solution. Furthermore, intra-AcbSh muscimol significantly increased intake of an
      ethanol-sucrose mixture. These results demonstrate that activating GABA(A)
      receptors in the vicinity of the AcbSh can have opposite effects on the intake of
      different caloric substances and are consistent with the possibility that
      GABAergic circuits in the AcbSh may play a role in mediating voluntary ethanol
      intake.

PMID- 20804791
TI  - V-Xtractor: an open-source, high-throughput software tool to identify and extract
      hypervariable regions of small subunit (16S/18S) ribosomal RNA gene sequences.
AB  - V-Xtractor (http://www.cmde.science.ubc.ca/mohn/software.html) uses Hidden Markov
      Models to locate, verify, and extract defined hypervariable sequence segments (V1
      V9) from bacterial, archaeal, and fungal small-subunit rRNA sequences. With a
      detection efficiency of 99.6% and low susceptibility to false-positives, this
      tool refines data reliability and facilitates subsequent analysis in community
      assays.

PMID- 20804792
TI  - Oxidative stress in anxiety and comorbid disorders.
AB  - Anxiety disorders, depression, and alcohol use disorder are common
      neuropsychiatric diseases that often occur together. Oxidative stress has been
      suggested to contribute to their etiology. Oxidative stress is a consequence of
      either increased generation of reactive oxygen species or impaired enzymatic or
      non-enzymatic defense against it. When excessive it leads to damage of all major
      classes of macromolecules, and therefore affects several fundamentally important
      cellular functions. Consequences that are especially detrimental to the proper
      functioning of the brain include mitochondrial dysfunction, altered neuronal
      signaling, and inhibition of neurogenesis. Each of these can further contribute
      to increased oxidative stress, leading to additional burden to the brain. In this
      review, we will provide an overview of recent work on oxidative stress markers in
      human patients with anxiety, depressive, or alcohol use disorders, and in
      relevant animal models. In addition, putative oxidative stress-related mechanisms
      important for neuropsychiatric diseases are discussed. Despite the considerable
      interest this field has obtained, the detailed mechanisms that link oxidative
      stress to the pathogenesis of neuropsychiatric diseases remain largely unknown.
      Since this pathway may be amenable to pharmacological intervention, further
      studies are warranted.

PMID- 20804793
TI  - Halophilic anaerobic fermentative bacteria.
AB  - In hypersaline environments bacteria are exposed to a high osmotic pressure
      caused by the surrounding high salt concentrations. Halophilic microorganisms
      have specific strategies for balancing the osmotic pressure and surviving in
      these extreme conditions. Halophilic fermentative bacteria form taxonomically and
      phylogenetically a coherent group mainly belonging to the order Halanaerobiales.
      In this review, halophilic anaerobic fermentative bacteria in terms of taxonomy
      and phylogeny, special characteristics, survival strategies, and potential for
      biotechnological applications in a wide variety of branches, such as production
      of hydrogen, are discussed.

PMID- 20804794
TI  - Limited beneficial effects of perfluorocarbon emulsions on encapsulated cells in
      culture: experimental and modeling studies.
AB  - Due to the high solubility of oxygen in perfluorocarbons (PFCs), these compounds
      have been explored for improved cell and tissue oxygenation. The goal of this
      study is to investigate the effects of a PFC emulsion on cellular growth and
      function in a tissue engineered construct. A perfluorotributylamine (PFTBA)
      emulsion was co-encapsulated at 10 vol% with mouse betaTC-tet insulinoma cells in
      calcium alginate beads and cultured under normoxic and severely hypoxic
      conditions. The number of metabolically active cells and the induced insulin
      secretion rate were measured over time for up to 16 days. Results showed no
      significant effect of PFTBA relative to the PFTBA-free control. The alginate-PFC
      cell system was also modeled mathematically, and simulations tracked the number
      of viable cells over time under the same conditions used experimentally.
      Simulations revealed only a small, likely experimentally undetectable difference
      in cell density between the PFC-containing and PFC-free control beads. It is
      concluded that PFTBA up to 10 vol% has no significant effect on the growth and
      function of encapsulated betaTC-tet cells under normoxic and hypoxic conditions.

PMID- 20804795
TI  - Biodegradation of mixture of phenol and formaldehyde in wastewater using a single
      basin MSCR process.
AB  - A novel moving-bed sequential continuous-inflow reactor (MSCR) was developed and
      investigated for the degradation of high concentrations of phenol and
      formaldehyde. Results indicated the MSCR could simultaneously remove greater than
      99% of the target compounds for concentrations up to 1300 mgL-1 each
      (corresponding to the loading rate of 1.04 kgm-3d-1), and around 96% of the
      chemical oxygen demand of ~4800 mgL-1 with a 6-h cycle time. An increase of the
      inlet concentrations to 1500 mgL-1 (loading rates of 1.2 kgm-3d-1), however,
      caused a slight reduction in the removal efficiency. The MSCR handled hydraulic
      shock loads of up to three times the normal flow rate without adversely affecting
      the elimination performance of the contaminants. These unique features, combined
      with the efficient and compact nature of the process, thus recommend MSCR as a
      promising technique for the removal of mixture of toxic compounds in a single
      basin bioreactor.

PMID- 20804796
TI  - Polyion complex micelle MRI contrast agents from poly(ethylene glycol)-b-poly(l
      lysine) block copolymers having Gd-DOTA; preparations and their control of T(1)
      relaxivities and blood circulation characteristics.
AB  - The current study synthesized macromolecular magnetic resonance imaging (MRI)
      contrast agents constituted of the poly(ethylene glycol)-b-poly(L-lysine) block
      copolymer (PEG-P(Lys)). A chelate group, 1,4,7,10-tetraazacyclododecane-1,4,7,10
      tetraacetic acid (DOTA), was attached to the primary amino group of the block
      copolymer in desired contents. Gd-DOTA-based macromolecular contrast agents were
      prepared from PEG-P(Lys) having DOTA (PEG-P(Lys-DOTA) and Gd(III) ions. All of
      the PEG-P(Lys) block copolymers having gadolinium ions (PEG-P(Lys-DOTA-Gd))
      showed higher T(1) relaxivity (per gadolinium), r(1)=5.6-7.3mM(-1)s(-1), than
      that of a low-molecular-weight gadolinium-chelate, diethylenetriaminepentaacetic
      acid-gadolinium(III) (Gd-DTPA) at 9.4T. The study prepared the polyion complex
      (PIC) micelles from the amino groups of the lysine units and an oppositely
      charged polyanion, poly(methacrylic acid) or dextran sulfate, in an aqueous
      medium. In contrast, the fully DOTA-attached PEG-P(Lys-DOTA-Gd) formed a PIC with
      a polycation. Compared with partially DOTA-attached cationic PEG-P(Lys-DOTA-Gd),
      this PIC micelle yielded a forty percent decrease of r(1). This r(1) decrease was
      considered to result from a change in the accessibility of water molecules to
      gadolinium ions in the micelles' inner core. The r(1) was decreased upon
      formation of the PIC micelle, and this change proved that our concept worked in
      vitro. Blood-circulation characteristics of PIC micelles were controlled by means
      of changing the molecular weight of the counter anion. The PIC micelles
      accumulated in tumor tissues, and MRI study showed T1W image of axial slice of
      tumor area was significantly enhanced at 24h after the injection.

PMID- 20804798
TI  - Altered myocardial expression of ghrelin and its receptor (GHSR-1a) in patients
      with severe heart failure.
AB  - Ghrelin is a peptide hormone mainly produced by the stomach, which strongly
      stimulates the release of growth hormone (GH) via the GH secretagogue receptor 1a
      (GHSR-1a) located in the hypothalamus. It has been reported to exert performance
      enhancing effects on myocardial function, and as both ghrelin and GHSR-1a are
      expressed in myocardial tissues, the ghrelin system may have a direct GH
      independent impact on cardiac function. We intended to investigate the expression
      of ghrelin and its receptor GHSR-1a in different myocardial areas of patients
      with chronic heart failure (CHF) as compared to heart-healthy subjects to better
      define the role of the ghrelin signaling system in the networks regulating
      cardiac function and its potential as a target for diagnosis and/or treatment of
      CHF. Myocardium biopsies of 12 patients undergoing heart transplantation and
      suffering from CHF were obtained. Expression of both ghrelin and GHSR-1a was
      assessed by means of immunohistochemistry and real-time PCR. Expression of
      ghrelin was significantly decreased in CHF hearts both in atrium and ventricles
      in comparison to the control hearts (p<0.05). The expression of the GHS-1a
      receptor was significantly increased in the CHF biopsies as compared to controls
      (p<0.05). No significant differences were found between the anatomical areas
      studied. Expression of myocardial ghrelin and GHSR-1a is directly associated with
      myocardial function: CHF hearts exhibit an impaired ghrelin production which
      might reflect maladaptive processes and an - probably compensatory - increase in
      GHSR-1a expression. These findings may open up new perspectives regarding the
      potential of ghrelin signaling as a target for pharmacological modulation.

PMID- 20804797
TI  - Regulation of gastric hormones by systemic rapamycin.
AB  - The mammalian target of rapamycin (mTOR), an evolutionarily conserved serine
      threonine kinase, is an intracellular fuel sensor critical for cellular energy
      homeostasis. Gastrointestinal endocrine cells play a vital role in the regulation
      of energy balance by secreting hormones that inform the brain about energy
      supply. Here we showed the localization of mTOR signaling molecules in more than
      90% of gastric ghrelin cells and 36+/-3% of gastrin cells, while no somatostatin
      positive cell showed phospho-S6K1 immunoreactivity. Inhibition of mTOR
      significantly stimulated expression of gastric ghrelin mRNA and protein, and the
      concentration of plasma ghrelin (2.06+/-0.34 ng/ml vs. 12.53+/-3.9 ng/ml,
      p<0.05), inhibited gastrin synthesis and secretion (75.01+/-6.71 pg/ml vs.
      54.04+/-3.65 pg/ml, p<0.05), but had no effect on somatostatin production
      (165.2+/-25.07 pg/ml vs. 178.9+/-29.14 pg/ml, p=0.73). Gastric mTOR is a gastric
      sensor whose activity is linked to the differential regulation of gastric hormone
      production and release.

PMID- 20804799
TI  - Morphological evidence for the involvement of microglial p38 activation in CGRP
      associated development of morphine antinociceptive tolerance.
AB  - Calcitonin gene-related peptide (CGRP) exerts an effect on the development of
      morphine antinociceptive tolerance, which may in part involve the activation of
      p38 kinase. In the present study, we investigated the temporal expression and
      spatial distribution of p38 phosphorylation as well as their possible regulation
      by CGRP receptor signaling following chronic morphine treatment. A 7-day
      intrathecal treatment with morphine (15 MUg/day) produced tolerance to its
      analgesic effects as well as a rightward shift in the dose-response curve to its
      antinociceptive effects. This treatment time-dependently increased p38
      phosphorylation in the spinal dorsal horn, as shown by phosphorylated p38
      immunoreactive (p-p38-ir) cell counts. The increased phosphorylation occurred
      first in superficial layers of the spinal dorsal horn and then extended to deeper
      laminae. Interestingly, accompanying the development of morphine tolerance, p-p38
      ir cells, identified as microglia, displayed hypertrophy and increased number of
      branched processes, suggesting their activation. These various behavioral and
      morphological changes were blocked by the intrathecal treatment with BIBN4096BS,
      a non-peptide CGRP receptor antagonist. These data provide additional
      morphological evidence in support of a role for CGRP in the development of
      morphine antinociceptive tolerance, possibly by regulating the expression and
      distribution of p38 phosphorylation in microglia.

PMID- 20804800
TI  - Open conformation of adipokinetic hormone receptor from the malaria mosquito
      facilitates hormone binding.
AB  - Insect flight requires rapid mobilization of energy reserves during flight, which
      is mediated and regulated by hormonal control via adipokinetic hormones. The
      structure of the G-protein receptors to which these hormones bind, are crucial in
      understanding many of the physiological processes in which they play a central
      role. To date no 3D structure of an insect G-protein coupled receptor (GPCR) is
      available. Here, the first models of the 3D structures of a GPCR from the malaria
      mosquito are presented. Homology modeling of the receptor identified from the
      genome of Anopheles gambiae was used to construct two models of the receptor. The
      7 transmembrane helical bundles of these two models are based on the crystal
      structures of beta2-adrenergic receptor and rhodopsin. The flexible loop regions
      were modeled using high temperature simulated annealing and constrained molecular
      dynamic simulations. The two receptor models differ in a number of critical
      features, the most important of which is that the rhodopsin-based model has a
      'closed' structure while the beta2-based structure is 'open'. The 'open'
      conformation provides easy access of the hormone to the binding pocket. Docking
      calculations with the insect adipokinetic hormones, AKH-1 (pGlu-Leu-Thr-Phe-Thr
      Pro-Ala-Trp-NH(2)) from the malaria mosquito and Del-CC (pGlu-Lys-Asn-Phe-Ser-Pro
      Asn-Trp-Gly-Asn-NH(2)) from the blister beetle showed that while the binding
      motif of the two is similar, AKH-1 has more than 30 times higher affinity than
      Del-CC, which strongly suggests that the binding is specific, and that the
      correct binding site was identified. Using these models it is possible to design
      antagonists, which block the binding site and are thus species-specific
      insecticides.

PMID- 20804801
TI  - Immunologic properties of human dermal fibroblasts.
AB  - Human dermal fibroblasts are known not to express human leukocyte antigen (HLA)
      DR message or protein in the absence of interferon (IFN)-gamma. To use allogeneic
      dermal fibroblasts for cell therapy, as a revalidation, the cells at passage 12
      were analyzed for HLA-DR mRNA and surface protein. Although no significant HLA-DR
      surface protein was found, HLA-DR mRNA expression was observed, without
      interferon-gamma. At an early passage, although HLA-DR surface protein was not
      found, prominent expression of HLA-DR mRNA was observed without IFN-gamma
      stimulation, which was not typical of dermal fibroblasts studied so far.
      Intracytoplasmic HLA-DR protein was also not detected, which suggests that the
      mRNA was not translated. There was no marked stimulation of T-cell proliferation
      by the fibroblasts in the absence or presence of IFN-gamma. Interestingly,
      indoleamine dioxygenase, a molecule involved in immunosuppression, was also
      expressed in dermal fibroblasts in the absence of IFN-gamma.

PMID- 20804802
TI  - Knowledge and attitudes regarding influenza vaccination among nurses: a research
      review.
AB  - INTRODUCTION: Influenza vaccination rates among nurses remain suboptimal despite
      health authority recommendations in many countries and several vaccination
      campaign programmes to encourage nurses to be vaccinated in many institutions. We
      reviewed published studies investigating nurses' knowledge and attitudes towards
      influenza vaccination to establish what is known about the determinants of
      nurses' influenza vaccination practices. METHODS: Relevant articles published up
      to July 2010 were identified through multiple databases (CINAHL, MEDLINE, PubMed,
      EMBASE, BNI, HMIC, PsycINFO, CMAC, and CNJ) using predetermined search
      strategies. Review of the titles and abstracts revealed 182 of 254 references
      were not relevant. Of 45 full papers reviewed, 32 did not report nurse data
      separately and one was a duplicate report of a study. RESULTS: We included 12
      research studies which had investigated the relationship between knowledge and
      attitudes towards influenza vaccination and nurses' vaccination practices
      published between 2003 and 2010. All the studies were descriptive and relied upon
      self-report data. The findings of this review indicate a relationship between
      knowledge, attitudes and vaccination practices of nurses. There were three main
      findings: first, there was a strong association between nurses' knowledge of
      influenza and vaccination and their vaccination status; second, the surveys
      showed a positive relationship between perceptions of influenza as a serious
      illness and vaccination as effective and safe and a positive vaccination status;
      and third, there was a relationship between nurses' vaccination status and their
      reported promotion of vaccination to their patients. CONCLUSION: This review
      indicates that higher knowledge and positive attitudes towards influenza
      vaccination have a significantly positive association with vaccination coverage
      among nurses. Further studies are needed to identify influences on nurses'
      attitudes and practices regarding influenza vaccination and the personal,
      organizational, and situational factors that influence the uptake of influenza
      vaccine by nurses.

PMID- 20804803
TI  - Knowledge of vaccination of allergic children among Italian primary care
      pediatricians, hospital pediatricians and pediatric residents.
AB  - A cross-sectional survey of Italian pediatricians and pediatric residents was
      carried out between 15 September and 18 October 2008 in order to evaluate their
      knowledge concerning the administration of vaccines to children with suspected or
      proved allergies. Of the 750 physicians who accepted to participate (620
      pediatricians and 130 residents), 630 (84.0%; 407 females; mean age 43.5 +/- 11.2
      years) returned completed questionnaires: 268 primary care pediatricians (42.5%),
      244 hospital pediatricians (38.8%), and 118 pediatric residents (18.7%).
      Knowledge concerning the vaccination of children with suspected or proved
      allergies was far from optimal, with the poorest knowledge being shown by the
      pediatric residents and no difference between the primary care and hospital
      pediatricians. Since pediatricians are the main parents' advisors regarding
      vaccinations, these results indicate an urgent need for educational programmes
      (especially for residents) and evidence-based guidelines concerning vaccinations
      in children with suspected or proved allergies.

PMID- 20804804
TI  - Design of a robust infrastructure to monitor the safety of the pandemic A(H1N1)
      2009 vaccination program in Taiwan.
AB  - On November 1, 2009, Taiwan began a nationwide pandemic A(H1N1) 2009 vaccine
      ("H1N1 vaccine") program to control the influenza pandemic. Timely assessment of
      immunization safety during this mass vaccination campaign was a public health
      priority. Therefore, the government developed a national postlicensure safety
      surveillance strategy to identify and evaluate new, unexpected, or prioritized
      adverse events in recipients of H1N1 vaccine in near real-time. We describe the
      design and methodology of this new safety assessment infrastructure, address
      challenges encountered, and its potential future use for routine vaccine
      pharmacovigilance in Taiwan.

PMID- 20804805
TI  - Safety assessment of EPA-rich oil produced from yeast: Results of a 90-day
      subchronic toxicity study.
AB  - The safety of eicosapentaenoic acid (EPA) oil produced from genetically modified
      Yarrowia lipolytica yeast was evaluated following 90 days of exposure. Groups of
      rats received 0 (olive oil), 98, 488, or 976 mg EPA/kg/day, or GRAS fish oil or
      deionized water by oral gavage. Rats were evaluated for in-life, neurobehavioral,
      anatomic and clinical pathology parameters. Lower serum cholesterol (total and
      non-HDL) was observed in Medium and High EPA and fish oil groups. Lower HDL was
      observed in High EPA and fish oil males, only at early time points. Liver weights
      were increased in High EPA and Medium EPA (female only) groups with no associated
      clinical or microscopic pathology findings. Nasal lesions, attributed to oil in
      the nasal cavity, were observed in High and Medium EPA and fish oil groups. No
      other effects were attributed to test oil exposure. Exposure to EPA oil for 90
      days produced no effects at 98 mg EPA/kg/day and no adverse effects at doses up
      to 976 mg EPA/kg/day. The safety profile of EPA oil was comparable to that of
      GRAS fish oil. These results support the use of EPA oil produced from yeast as a
      safe source for use in dietary supplements.

PMID- 20804806
TI  - Integrating variability in half-lives and dietary intakes to predict mercury
      concentration in hair.
AB  - Methylmercury (MeHg) is a bioaccumulative environmental toxin that exerts its
      effect on fetal and infant neurodevelopment. Mercury concentration in hair is a
      good biomarker of MeHg accumulation in the body, with seafood being the main
      source of MeHg in humans. Therefore, modeling the link between food intake and
      mercury concentration in hair is a key step in assessing the risk of MeHg
      exposure. Using repeated measurements of diet and mercury concentration in hair,
      we studied 125 French pregnant women who consumed seafood (e.g., fish, mollusks
      and crustaceans) and compared their individual estimated dietary MeHg intakes
      with their hair mercury concentrations. We used a one-compartment toxicokinetic
      model for these comparisons. We integrated and estimated the between-person
      variability in MeHg half-life into the model. In a second model, we took into
      account an intra-individual MeHg intake variability to improve the performance of
      the toxicokinetic model.

PMID- 20804807
TI  - Plant natural variability may affect safety assessment data.
AB  - Before market introduction, genetic engineered (GE) food products, like any other
      novel food product, are subjected to extensive assessment of their potential
      effects on human health. In recent years, a number of profiling technologies have
      been explored aiming to increase the probability of detecting any unpredictable
      unintended effect and, consequently improving the efficiency of GE food safety
      assessment. These techniques still present limitations associated with the
      interpretation of the observed differences with respect to their biological
      relevance and toxicological significance. In order to address this issue, in this
      study, we have performed 2D-gel electrophoresis of five different ears of five
      different MON810 maize plants and of other five of the non-transgenic near
      isogenic line. We have also performed 2D-gel electrophoresis of the pool of the
      five protein extractions of MON810 and control lines. We have notice that, in
      this example, the exclusive use of data from 2D-electrophoresed pooled samples,
      to compare these two lines, would be insufficient for an adequate safety
      evaluation. We conclude that, when using "omics" technologies, it is extremely
      important to eliminate all potential differences due to factors not related to
      the ones under study, and to understand the role of natural plant-to-plant
      variability in the encountered differences.

PMID- 20804808
TI  - Response rate of lorazepam in catatonia: a developing country's perspective.
AB  - BACKGROUND: Catatonia is a syndrome characterized by concurrent motor, emotional,
      and behavioral symptoms. Short-term benzodiazepine administration and
      electroconvulsive therapy have proven to be safe and useful for treatment of this
      syndrome. AIMS: This study aimed to explore the evidence of effectiveness of
      lorazepam as a first line treatment for catatonia in a tertiary psychiatry centre
      in India given the lack of facilities for ECT in primary care centers of
      developing countries. We examined the response rate of lorazepam in Catatonia.
      METHODOLOGY: Clinical charts of 107 inpatients, admitted over a duration of two
      years, with a primary diagnosis of catatonia were examined for response with
      lorazepam trial. Trial was considered as having received 3-6 mg per day of
      lorazepam for at least 3 days. RESULTS: Among the patients who were given
      lorazepam treatment, 32 out of 99 (32.3%) showed response (with complete
      resolution of catatonic symptoms). Improvement in catatonic symptoms was seen in
      68 out of 99 (68.7%) patients. CONCLUSIONS: Lorazepam is cost effective and could
      rapidly relieve catatonic signs, even without the use of ECT in a significant
      proportion of catatonic patients. Its early use can prevent disease progression
      and complications.

PMID- 20804809
TI  - Quality of life and cognitive dysfunction in people with schizophrenia.
AB  - The main purpose of the present study was to examine the relationship between
      quality of life (QOL) and cognitive dysfunction in schizophrenia. Subjects were
      61 stabilized outpatients. Quality of life and cognitive function were assessed
      using the Quality of Life Scale (QLS) and the Brief Assessment of Cognition in
      Schizophrenia (BACS), respectively. Clinical symptoms were evaluated with the
      Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for
      Schizophrenia (CDSS). The BACS composite score and the BACS Verbal memory score
      were positively correlated with the QLS total score and two subscales. The BACS
      Attention and speed of information processing score had positive correlation with
      the QLS total and all the subscales scores. The PANSS Positive and Negative
      syndrome scores also had significant correlations with the QLS total score and
      all of the subscales. In addition, the CDSS score was negatively correlated with
      the QLS total score and some of the subscales. Stepwise regression analysis
      showed that the BACS Attention and speed of information processing score was an
      independent predictor of the QLS total score but it was less associated with the
      QLS than the PANSS Negative syndrome score and the CDSS score. The results
      suggest that negative and depressive symptoms are important factors on patients'
      QOL and also support the view that cognitive performance provides a determinant
      of QOL in patients with schizophrenia.

PMID- 20804810
TI  - Differential roles of phospholipases A2 in neuronal death and neurogenesis:
      implications for Alzheimer disease.
AB  - The involvement of phospholipase A(2) (PLA(2)) in Alzheimer disease (AD) was
      first investigated nearly 15 years ago. Over the years, several PLA(2) isoforms
      have been detected in brain tissue: calcium-dependent secreted PLA(2) or sPLA(2)
      (IIA, IIC, IIE, V, X, and XII), calcium-dependent cytosolic PLA(2) or cPLA(2)
      (IVA, IVB, and IVC), and calcium-independent PLA(2) or iPLA(2) (VIA and VIB).
      Additionally, numerous in vivo and in vitro studies have suggested the role of
      different brain PLA(2) in both physiological and pathological events. This review
      aimed to summarize the findings in the literature relating the different brain
      PLA(2) isoforms with alterations found in AD, such as neuronal cell death and
      impaired neurogenesis process. The review showed that sPLA(2)-IIA, sPLA(2)-V and
      cPLA(2)-IVA are involved in neuronal death, whereas sPLA(2)-III and sPLA(2)-X are
      related to the process of neurogenesis, and that the cPLA(2) and iPLA(2) groups
      can be involved in both neuronal death and neurogenesis. In AD, there are reports
      of reduced activity of the cPLA(2) and iPLA(2) groups and increased expression of
      sPLA(2)-IIA and cPLA(2)-IVA. The findings suggest that the inhibition of cPLA(2)
      and iPLA(2) isoforms (yet to be determined) might contribute to impaired
      neurogenesis, whereas stimulation of sPLA(2)-IIA and cPLA(2)-IVA might contribute
      to neurodegeneration in AD.

PMID- 20804811
TI  - Potential protective effects of quercetin and curcumin on paracetamol-induced
      histological changes, oxidative stress, impaired liver and kidney functions and
      haematotoxicity in rat.
AB  - The present study was carried out to evaluate the potential protective role of
      quercetin and curcumin against paracetamol-induced oxidative injury, liver damage
      and impairment of kidney function, as well as haematotoxicity in rats. Also, N
      acetylcysteine was used to evaluate the potency of quercetin and curcumin.
      Paracetamol caused an elevation in thiobarbituric acid-reactive substances
      (TBARS) paralleled with significant decline in glutathione peroxidase,
      glutathione S-transferase, superoxide dismutase and catalase activities (in
      plasma, brain, lung, heart, liver, kidney and testes) and glutathione content (in
      lung, liver and kidney). The apparent oxidative injury was associated with
      evident hepatic necrosis confirmed in histological examination, elevated plasma
      transmainases, alkaline phosphatase and lactate dehydrogenase. Paracetamol
      reduced plasma total protein, albumin and globulin, while increased bilirubin,
      urea and creatinine, and induced haematotoxicity. The presence of quercetin or
      curcumin with paracetamol successfully mitigated the rise in TBARS and restored
      the activities of antioxidant enzymes compared to the group treated with both
      paracetamol and N-acetylcysteine. They also protected liver histology, normalized
      liver and kidney functions, which was more pronounced with curcumin. Therefore,
      it can be concluded that concomitant administration of quercetin or curcumin with
      paracetamol may be useful in reversing the toxicity of the drug compared to N
      acetylcysteine.

PMID- 20804812
TI  - Inhibition of angiogenesis by quercetin in tamoxifen-resistant breast cancer
      cells.
AB  - Acquired resistance to tamoxifen (TAM) is a serious therapeutic problem among
      breast cancer patients. Previously, we have reported that TAM-resistant MCF-7
      cells (TAMR-MCF-7 cells) showed increased angiogenic intensity through Pin1
      dependent vascular endothelial growth factor (VEGF) production. Among six
      flavonoids tested in the current study, VEGF gene transcription in MCF-7 cells
      with stable Pin1 overexpression was inhibited most effectively by quercetin.
      Reporter gene assays using minimal reporters containing hypoxia response elements
      and activator protein-1 (AP-1) elements revealed that the activities of hypoxia
      inducible factor-1alpha (HIF-1alpha) and AP-1, key transcription factors for VEGF
      gene transcription, were suppressed by quercetin. Western blot analyses confirmed
      that the increased nuclear levels of c-Jun and HIF-1alpha in TAMR-MCF-7 cells
      were blocked by quercetin. Moreover, quercetin inhibited the enhanced VEGF
      secretion and Pin1 expression in TAMR-MCF-7 cells, which was dependent on its
      phosphatidyl inositol 3-kinase inhibiting effect. Chick chorioallantoic membrane
      assays demonstrated that the enhanced angiogenesis intensity of TAMR-MCF-7 cells
      was also suppressed significantly by quercetin. These results demonstrate that
      quercetin may have therapeutic potential for the treatment of TAM-resistant
      breast cancer via Pin1 inhibition.

PMID- 20804813
TI  - Effect of olive fruit fly infestation on the quality of olive oil from Chemlali
      cultivar during ripening.
AB  - Olive fruits are seriously deteriorated by pre and post harvest damage due to the
      attack of insects, such as Bactrocera olaea, which strongly alters the quality of
      olives. Olives from Chemlali cultivar were collected and divided into different
      groups according to the presence or absence of infestation (0%, 5%, 10%, 15% and
      100%) by the olive fruit fly (B. olaea). The infestation of this pest has been
      studied to evaluate its influence on virgin olive oil quality (free acidity,
      K(232) and K(270), fatty acids composition, pigment concentration, organoleptic
      characteristics, phenolic content, and antioxidant power). Results showed that
      both attacks by B. oleae and maturity process affected the quantitative and
      qualitative composition of the oil. These analyses demonstrated that the degree
      of fly attack was positively correlated with free acidity, the values of this
      parameter increase from 0.6 to 1.5 and 3.4, at the infestation levels 10%, 15%
      and 100%, respectively (R(2)=0.7418, P<0.05), and negatively related to the
      phenolic content which was always lower at the 100% infestation level
      (R(2)=0.9155, P<0.05), and consequently, the organoleptic characteristics. In
      addition, the infestation by olive fly did not cause an important change in the
      fatty acid composition while it is clear that fatty acids levels change in
      relation to the fruit repining stage. The antioxidant activity decreased during
      maturation, it was correlated to the total phenol content and the fruit
      infestation level.

PMID- 20804814
TI  - Study on antioxidant activity of common dry fruits.
AB  - This study investigates the antioxidant activity of different dry fruits
      (almonds, walnut, cashew nut, raisins, chironji) through several chemical and
      biochemical assays: reducing power, lipid peroxidation damage in biomembranes,
      determination of antioxidant enzymes activity (SOD and CAT). To estimate the
      total phenolic content, the assay using Folin-Ciocalteu reagent was used. The
      EC(50) values were calculated for all the methods in order to evaluate the
      antioxidant efficiency of each dry fruit. The results obtained were quite
      heterogenous, revealing significant differences among the dry fruits. The
      methanolic extract of walnut showed the higher value of antioxidant activity
      based on lipid peroxidation assay. The higher phenolic content was found in
      walnuts followed by almonds cashew nut, chironji and least phenolic content was
      found in raisins. Walnut revealed the best antioxidant properties, presenting
      lower EC(50) values in all assays except in antioxidant enzymatic activity.

PMID- 20804815
TI  - Ameliorative effect of sesame lignans on nicotine toxicity in rats.
AB  - Nicotine causes oxidative and genotoxic damages in the tissues leading to several
      diseases. Any strategy through natural diet that prevents or slows the
      progression and severity of nicotine toxicity has a significant health impact.
      This work is designed to investigate natural antioxidants that play effective
      protective role against nicotine-induced toxicity. Experiments were conducted on
      male albino rats by injecting nicotine tartrate (3.5 mg/kg body wt./day for 15
      days) subcutaneously and thereby supplementing sesame lignans (0.1 g/100g diet
      and 0.2 g/100g diet) orally to them. Significant (P<0.01) increase of total
      cholesterol, triglyceride, LDL-cholesterol, VLDL-cholesterol, decrease of HDL
      cholesterol, decrease in antioxidant enzymes and increase in concentration of
      lipid peroxidative product has been observed in plasma due to nicotine toxicity.
      Significant (P<0.01) decrease of total DNA contents and highly significant
      (P<0.001) DNA damage of liver tissue is also observed on nicotine treatment.
      Sesame lignans minimizes the above mentioned effects. The nicotine-induced
      oxidative and genotoxic damages on the tissues can be effectively attenuated by
      sesame lignans supplemented diet.

PMID- 20804816
TI  - Structure-based investigation on the binding interaction of hydroxylated
      polybrominated diphenyl ethers with thyroxine transport proteins.
AB  - Polybrominated diphenyl ethers (PBDEs) have been shown to alter thyroid hormone
      level in experimental animals. One of the possible mechanisms for hormone
      disruption is the competitive binding of hydroxylated PBDEs (OH-PBDEs) with
      hormone transport proteins. In this study, binding interaction of 14 diversely
      structured OH-PBDEs with two thyroxine transport proteins was investigated by
      fluorescence displacement assay, circular dichroism, and molecular docking.
      Binding affinity of the 14 OH-PBDEs with transthyretin (TTR) and thyroxine
      binding globulin (TBG) was measured by competitive fluorescence displacement
      assay. The binding constant was found to fall in the range of 1.4 x 107 M and 6.9
      x 108 M-1 for TTR, and between 6.5 x 106 M-1 and 2.2 x 108 M-1 for TBG. Binding
      affinity increased significantly with bromination number from 1 to 4, whereas 5-
      and 6-brominated diphenyl ethers did not show any further increase. Protein
      secondary structural change of TTR and TBG upon binding with 5-OH-BDE-047 was
      investigated by circular dichroism. The spectral change displayed a pattern
      similar to the one with thyroxine, suggesting that the environmental chemical
      binds to the two proteins at the same sites as the hormone. In molecular docking
      analysis, a ligand-binding channel in TTR was revealed for OH-PBDEs binding,
      which appeared to be mostly hydrophobic inside but guarded by positively charged
      residue Lys15 at the entrance. Binding affinity of the 14 OH-PBDEs with TTR could
      be rationalized reasonably well by their pocket binding mode and hydrophobic
      characteristics. Based on the binding constant obtained in this work, possibility
      of in vitro competitive displacement of thyroid hormones from the transport
      proteins by OH-PBDEs was evaluated.

PMID- 20804817
TI  - Difference between smokers and non-smokers in the corpus callosum volume.
AB  - The purpose of this study was to analyze the effects of smoking on corpus
      callosum volume. In addition, the relationships between smoking duration, smoking
      frequency, and corpus callosum volume were analyzed. Magnetic resonance brain
      images were acquired for 58 normal Korean men (30 smokers (age 32.82+/-14.12
      years) and 28 non-smokers (age 35.49+/-13.11 years)). The corpus callosum volume
      was measured using Brain Voyager 2000S/W and was normalized by intracranical
      volume, which was calculated using cerebral sizes. The corpus callosum volume for
      smokers was significantly smaller than that for non-smokers. Also, there was a
      negative correlation between corpus callosum volume and smoking duration. The
      change of white matter volume (e.g., corpus callosum) might be a primary factor
      for characterizing the effects of smoking.

PMID- 20804818
TI  - A free-radical scavenger protects the neural progenitor cells in the dentate
      subgranular zone of the hippocampus from cell death after X-irradiation.
AB  - It has been elucidated that cognitive dysfunction following cranial radiotherapy
      might be linked to the oxidative stress-induced impairment of hippocampal
      neurogenesis that is mediated by proliferating neural stem or progenitor cells.
      The novel free-radical scavenger edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one)
      has been clinically used to reduce neuronal damage following ischemic stroke.
      Previously, we reported that the free-radical scavenger, edaravone, which is
      currently used to treat patients with brain ischemia, protected cultured human
      neural stem cells (NSCs) from radiation-induced cell death; the protective effect
      was observed more significantly in NSCs than in brain tumor cells. Here, in
      animal models, we demonstrate that edaravone protects neurons in the subgranular
      zone (SGZ) of the dentate gyrus of the hippocampus from cell death after
      irradiation. Moreover, edaravone protected spatial memory retention deficits as
      determined by Morris water maze tests. Our study may shed some light on the
      beneficial effects of free-radical scavengers in impaired neurogenesis following
      cranial radiation therapy.

PMID- 20804819
TI  - Angiogenesis but not neurogenesis is critical for normal learning and memory
      acquisition.
AB  - Aerobic exercise has been well established to promote enhanced learning and
      memory in both human and non-human animals. Exercise regimens enhance blood
      perfusion, neo-vascularization, and neurogenesis in nervous system structures
      associated with learning and memory. The impact of specific plastic changes to
      learning and memory performance in exercising animals are not well understood.
      The current experiment was designed to investigate the contributions of
      angiogenesis and neurogenesis to learning and memory performance by
      pharmacologically blocking each process in separate groups of exercising animals
      prior to visual spatial memory assessment. Results from our experiment indicate
      that angiogenesis is an important component of learning as animals receiving an
      angiogenesis inhibitor exhibit retarded Morris water maze (MWM) acquisition.
      Interestingly, our results also revealed that neurogenesis inhibition improves
      learning and memory performance in the MWM. Animals that received the
      neurogenesis inhibitor displayed the best overall MWM performance. These results
      point to the importance of vascular plasticity in learning and memory function
      and provide empirical evidence to support the use of manipulations that enhance
      vascular plasticity to improve cognitive function and protect against natural
      cognitive decline.

PMID- 20804820
TI  - Cortico-hippocampal hyperexcitability in synapsin I/II/III knockout mice: age
      dependency and response to the antiepileptic drug levetiracetam.
AB  - Synapsins (SynI, SynII, SynIII) are a multigene family of synaptic vesicle (SV)
      phosphoproteins implicated in the regulation of synaptic transmission and
      plasticity. Synapsin I, II, I/II and I/II/III knockout mice are epileptic and
      SYN1/2 genes have been identified as major epilepsy susceptibility genes in
      humans. We analyzed cortico-hippocampal epileptiform activity induced by 4
      aminopyridine (4AP) in acute slices from presymptomatic (3-weeks-old) and
      symptomatic (1-year-old) Syn I/II/III triple knockout (TKO) mice and aged-matched
      triple wild type (TWT) controls and assessed the effect of the SV-targeted
      antiepileptic drug (AED) levetiracetam (LEV) in reverting the epileptic
      phenotype. Both fast and slow interictal (I-IC) and ictal (IC) events were
      observed in both genotypes. The incidence of fast I-IC events was higher in
      presymptomatic TKO slices, while frequency and latency of I-IC events were
      similar in both genotypes. The major age and genotype effects were observed in IC
      activity, that was much more pronounced in 3-weeks-old TKO and persisted with
      age, while it disappeared from 1-year-old TWT slices. LEV virtually suppressed
      fast I-IC and IC discharges from 3-weeks-old TWT slices, while it only increased
      the latency of fast I-IC and IC activity in TKO slices. Analysis of I-IC events
      in patch-clamped CA1 pyramidal neurons revealed that LEV increased the
      inhibitory/excitatory ratio of I-IC activity in both genotypes. The lower LEV
      potency in TKO slices of both ages was associated with a decreased expression of
      SV2A, a SV protein acting as LEV receptor, in cortex and hippocampus. The results
      demonstrate that deletion of Syn genes is associated with a higher propensity to
      4AP-induced epileptic paroxysms that precedes the onset of epilepsy and
      consolidates with age. LEV ameliorates such hyper excitability by enhancing the
      inhibition/excitation ratio, although the effect is hindered in TKO slices which
      exhibit a concomitant decrease in the levels of the LEV receptor SV2A.

PMID- 20804821
TI  - Toll-like receptor 4 (TLR4), but not TLR3 or TLR9, knock-out mice have
      neuroprotective effects against focal cerebral ischemia.
AB  - Toll-like receptors (TLRs) are signaling receptors in the innate immune system
      that is a specific immunologic response to systemic bacterial infection. We
      investigated whether cerebral ischemia induced by the middle cerebral artery
      occlusion (MCAO) for 2 h differed in mice that lack a functional TLR3, TLR4, or
      TLR9 signaling pathway. TLR4, but not TLR3 or TLR9, knock-out (KO) mice had
      significantly smaller infarct area and volume at 24 h after ischemia-reperfusion
      (I/R) compared with wild-type mice. In addition, TLR4 KO mice improved in
      neurological deficits after I/R compared with wild-type mice. Moreover, we
      investigated the expression of TLR4 in the ischemic brain with
      immunohistochemistry. The number of TLR4-positive cells gradually increased from
      1 h after MCAO to 22 h after I/R. We also examined the localization of TLR4 in
      the ischemic area. TLR4 was localized with CD11b-positive microglial cells in the
      ischemic striatum and the number of CD11b-positive microglial cells was smaller
      in TLR4 KO mice than in wild-type mice. In addition, we investigated the
      translocation of NF-kappaB among TLR3, 4, and 9 KO mice after I/R injury using
      western blotting. NF-kappaB's p65 subunit was decreased in TLR4 KO mice compared
      to wild-type mice, but not TLR3 or 9 KO mice. These data suggest that TLR4
      knockout, but not TLR3 or TLR9 knockout, may play a neuroprotective role in
      ischemic brain injury induced by MCAO in mice.

PMID- 20804822
TI  - Does movement planning follow Fitts' law? Scaling anticipatory postural
      adjustments with movement speed and accuracy.
AB  - We wanted to determine whether movement planning followed Fitts' law by
      investigating the relationship between movement planning and movement performance
      in experienced dancers executing a typical classical ballet step in which the big
      toe was pointed to targets at different distances and of different widths so as
      to obtain several indices of difficulty (ID). Movement time, velocity and
      variability at the target were the variables of movement performance kinematics;
      movement planning was evaluated by analysis of anticipatory postural adjustments
      (APAs) to assess their modulation at different IDs. Movement time and peak of
      velocity were found to scale with the ID only when individual movement distance
      across target widths was entered into the analysis. APA magnitude and duration
      both scaled according to movement parameters but not in the same way. APA
      magnitude scaled with movement velocity, while APA duration was sensitive to the
      amplitude-to-accuracy ratio following the ID for movements performed in the
      shortest time interval when on-line feedback control is probably not available.
      Here we show that timing of muscle activation acts as an independent central
      command that triggers fine-tuning for speed-accuracy trade-off.

PMID- 20804823
TI  - Flash chromatography on cartridges for the separation of plant extracts: rules
      for the selection of chromatographic conditions and comparison with medium
      pressure liquid chromatography.
AB  - Empirical rules for the selection of chromatographic conditions on flash
      chromatography cartridges were developed, with an emphasis on gradient mode.
      These rules were then tested with separation of extracts from important medicinal
      plants including Curcuma xanthorrhiza, Piper nigrum and Salvia milthiorrhiza.
      Sepacore(r) cartridges enabled a good separation of compounds with a broad range
      of polarity, as typically found in plant extracts. The chromatographic resolution
      remained, however, lower than that achieved on classical columns packed with
      material of smaller particle size. For poorly soluble extracts, solid
      introduction gave better results than liquid injection.

PMID- 20804824
TI  - Flavonoid glycosides from Microtea debilis and their cytotoxic and anti
      inflammatory effects.
AB  - Two new 5-O-glucosylflavones, 5-O-beta-D-glucopyranosyl cirsimaritin (1) and 5,
      4'-O-beta-D-diglucopyranosyl cirsimaritin (2), four known flavonoids, cirsimarin
      (3), cirsimaritin (4), salvigenin (5), 4', 5-dihydroxy-7-methoxyflavone (6), and
      a norisoprenoid, vomifoliol (7), have been isolated from the aerial parts of
      Microtea debilis. All isolates were tested for cytotoxicity in human cancer cell
      lines (Hep G2, COLO 205, and HL-60) and anti-inflammatory activities in LPS
      treated RAW264.7 macrophages. Compound 6 was found to be a potent inhibitor to
      nitrite production in macrophages. Compounds 2, 4, 6, and 7 showed moderate anti
      proliferative activity against COLO-205 cells with IC(50) values of 7.1, 13.1,
      6.1, and 6.8 MUM, respectively.

PMID- 20804825
TI  - A novel hepatoprotective saponin from Celosia cristata L.
AB  - A new saponin, cristatain (1), together with four other saponins, celosin A (2),
      celosin B (3), celosin C (4) and celosin D (5) were isolated from the seeds of
      Celosia cristata L. (Amaranthaceae). Their structures were established by
      chemical and spectroscopic analyses. For the first time, the saponins were found
      in C. cristata L. In addition, compound 1 exhibited significant hepatoprotective
      effect on carbon tetrachloride (CCl(4))- and N,N-dimethylformamide (DMF)-induced
      hepatotoxicity in mice, which were evidenced by significant decreases in the
      values of asparate aminotransferase (AST), alanine aminotransferase (ALT) and
      alkaline phosphatase (ALP) of serum and histopathological examinations compared
      to controls.

PMID- 20804826
TI  - The effect of safranal on histamine (H(1)) receptors of guinea pig tracheal
      chains.
AB  - The effect of three concentrations of safranal on histamine (H(1)) receptors was
      tested on two groups of tracheal chains incubated with: 1) indomethacin, and 2)
      indomethacin, propranolol and atropine (n = 6). The EC(50) (effective
      concentration of histamine causing 50% of maximum response) obtained in the
      presence of chlorpheniramine and all concentrations of safranal in both groups
      were significantly greater than those of saline (p < 0.05 to p < 0.001). The
      EC(50) obtained in the presence of all concentrations of safranal and maximum
      response of its two higher concentrations (1.25 and 2.5 MUg/mL) in group 2 were
      greater than in group 1 (p < 0.05 to p < 0.001).

PMID- 20804827
TI  - The classical drug discovery approach to defining bioactive constituents of
      botanicals.
AB  - In this review, several recently identified biologically active principles of
      selected botanical dietary supplement ingredients are described, and were
      isolated using classical phytochemical chromatographic methods, with various
      spectroscopic procedures used for their isolation and structure elucidation. A
      central component of such an approach is "activity-guided fractionation" to
      monitor the compound purification process. In vitro assays germane to cancer
      chemoprevention were used to facilitate the work performed. Bioactive compounds,
      including several new substances, were characterized from acai (Euterpe
      oleracea), baobab (Adansonia digitata), licorice (Glycyrrhiza glabra), mangosteen
      (Garcinia mangostana), and noni (Morinda citrifolia). Many of these compounds
      exhibited quite potent biological activity, but tended to be present in their
      plant of origin only at low concentration levels.

PMID- 20804828
TI  - Anti-inflammatory, cyclooxygenase inhibitory and antioxidant activities of
      standardized extracts of Tridax procumbens L.
AB  - The standardized EtOAc, MeOH and 70% EtOH extracts of Tridax procumbens aerial
      parts showed significant inhibition of rat paw edema at a medium dose of 200mg/kg
      and the EtOAC extract was the most active. These extracts were standardized by
      HPLC with the help of chemical markers. Further, the extracts were evaluated for
      COX-1 and COX-2 inhibitory activity and EtOAc extract exhibited the highest
      inhibition of COX-1 and COX-2 at 50 MUg/mL. Cent aurein, centaureidin and
      bergenin were isolated as COX-1 and COX-2 inhibitory principles from the EtOAc
      extract. The extracts also exhibited antioxidant activity against DPPH and ABTS
      free radicals. The anti-inflammatory activity of T. procumbens aerial parts could
      be at least in part due to COX-1, COX-2 enzyme inhibition and free radical
      scavenging activities which may be attributed to the presence of flavonoids and
      other polyphenols in the extracts.

PMID- 20804829
TI  - Study on secondary metabolite content of Helleborus niger L. leaves.
AB  - Phytochemical investigation of Helleborus niger L. (Ranunculaceae) leaf methanol
      extract allowed to isolate a phenolic glucoside derivative and two flavonoid
      glycosides characterized as phenyllactic acid 2-O-beta-D-glucopyranoside (1),
      quercetin 3-O-2-(E-caffeoyl)-alpha-L-arabinopyranosyl-(1 -> 2)-beta-D
      glucopyranoside-7-O-beta-D-glucopyranoside (2), and kaempferol 3-O-alpha-L
      arabinopyranosyl-(1 -> 2)-beta-D-galactopyranoside-7-O-beta-D-glucopyranoside
      (3), respectively. Compounds 1 and 2 were isolated for the first time and their
      structural characterization was obtained on the basis of extensive NMR spectral
      studies.

PMID- 20804830
TI  - The effect of prefeeding on fixed-ratio pausing is jointly determined by past and
      upcoming reinforcer magnitudes.
AB  - Pausing within multiple fixed-ratio schedules differing in reinforcer magnitude
      is jointly controlled by both past and upcoming conditions of reinforcement.
      Abrupt shifts from a just-received large reinforcer to a signaled upcoming small
      reinforcer (i.e., a negative incentive shift) produce marked disruptions in
      responding, as indexed by extended pausing. The purpose of this experiment was to
      determine if reducing the level of food deprivation via prefeeding enhanced these
      disruptive effects. Five Long Evans rats lever-pressed according to a fixed-ratio
      schedule. Half of the components ended in a relatively large reinforcer (three 45
      mg food pellets) and half ended in a relatively small reinforcer (one pellet).
      Components alternated irregularly, yielding four transitions between reinforcers:
      small-small, small-large, large-small (the negative incentive shift), and large
      large. During five, 1-session prefeeding probes, rats were given 12 g of food in
      their home cages 1h prior to the start of the session. Under steady-state
      conditions, negative incentive shifts engendered the longest pausing. Prefeeding
      produced large absolute and relative increases in pausing during negative
      incentive shifts, and small increases in pausing in the other transitions. The
      results are interpreted within a resistance to change framework.

PMID- 20804831
TI  - Individual differences in the elevated plus-maze and the forced swim test.
AB  - The elevated plus-maze is an apparatus composed of enclosed and open (elevated)
      arms and time spent in the open arms by a rat can be increased/decreased by
      anxiolytic/anxiogenic agents. In the forced swim test, floating behavior is used
      as an index of behavioral despair and can be decreased by antidepressant agents.
      As the comorbidity between anxiety and depression is a remarkable issue in human
      behavioral disorders, a possible relationship between the behaviors seen in the
      cited tests is of great relevance. In the present study, fifty-four male rats
      (Rattus norvegicus) were submitted to a plus-maze session and to a 2-day forced
      swim protocol. According to their time in the open arms, they were divided into
      three groups: Low Open, Medium Open and High Open. Some plus-maze measures were
      found to be coherent with time in the open arms and are suggested to also be
      reliable anxiety indexes. In the forced swim test, the Low Open group showed
      decreases in floating duration from forced swim Session 1 to Session 2, an
      alteration opposite to that observed in the other groups (particularly, the
      Medium Open group). The Low Open group also showed increases in floating latency,
      again in sharp contrast with the alteration found in the other groups.
      Accordingly, positive and negative correlation were found between time in the
      open arms and floating duration and latency, respectively. Results are compared
      to previous studies and mediation of the effect by reactivity to aversive
      stimulation or alterations induced by open arm exposure is discussed.

PMID- 20804832
TI  - Salience modulation and associative inhibition interaction: short but not long
      exposure to similar stimuli protects the salience of the unique elements.
AB  - In three experiments, rats were given preexposure to two similar flavour
      compounds, AX and BX. Following preexposure, conditioning trials took place in
      which AX was paired with an illness-induced unconditioned stimulus. Animals that
      were given short alternated preexposure to AX and BX, showed higher
      generalization of conditioned aversion to AX to a new compound, AN, than animals
      that were given blocked preexposure (short and long) and long alternated
      preexposure (Experiments 1 and 2); and showed less preference for A when they
      were given a choice between A and X (Experiment 3). These results have been taken
      to indicate that the salience of the A element is well preserved after short
      alternated preexposure, but declines when preexposure goes on for some more
      trials. The results reported support the notion that perceptual learning is a
      multi-determined phenomenon that depends on salience modulation processes after
      relatively short preexposure, and on an associative inhibition mechanism after
      prolonged preexposure.

PMID- 20804833
TI  - Pro-IL-1beta accumulation in macrophages by alendronate and its prevention by
      clodronate.
AB  - Nitrogen-containing bisphosphonates (NBPs), anti-bone-resorptive drugs, exhibit
      inflammatory side effects (fever, jaw osteomyelitis or osteonecrosis, etc.). We
      previously reported that in mice: (i) a single intraperitoneal injection of
      alendronate (an NBP, 40 MUmol/kg or less) induces various inflammatory reactions,
      (ii) these effects, which are minimal in IL-1-deficient mice, can be prevented by
      co-administration of clodronate (a non-NBP, 40 MUmol/kg or less), and (iii)
      alendronate increases IL-1beta in tissues (liver, spleen, and lung), but
      strangely not in blood. Here, we found the following in mice. (a) The IL-1beta in
      tissues is pro-IL-1beta. (b) Unlike LPS, alendronate induces minimal activation
      of caspase-1 (pro-IL-1beta-processing enzyme). (c) The tissue pro-IL-1beta
      elevations are largely absent in macrophage-depleted mice. (d) In vitro, 100 MUM
      alendronate directly stimulates RAW 264 cells (murine macrophage-like cells) to
      produce pro-IL-1beta, and 1 MUM clodronate inhibits this effect. These results
      suggest that in mice: (i) the major pro-IL-1beta-producing cells in response to
      alendronate are macrophages, (ii) alendronate directly stimulates them to produce
      pro-IL-1beta, but the release of mature IL-1beta is below detectable levels due
      to insufficient activation of caspase-1, and (iii) clodronate inhibits the pro-IL
      1beta production by acting directly on macrophages, although the in vivo
      mechanism may differ from the in vitro one.

PMID- 20804834
TI  - Preparation, characterization and properties of partially hydrolyzed ethylene
      vinyl acetate copolymer films for controlled drug release.
AB  - In this study, partially hydrolyzed ethylene vinyl acetate (EVA) copolymers with
      three hydrolysis degrees (12.2%, 32.6% and 46.9%) were obtained by alkaline
      hydrolysis of EVA copolymer, characterized by Fourier-transform infrared
      spectroscopy (FTIR), (1)H NMR and gel permeation chromatography (GPC). Paclitaxel
      loaded and drug-free films based on the partially hydrolyzed EVA copolymers were
      fabricated. The swelling behaviors, crystallinities, mechanical properties of the
      fabricated films were investigated, and the effects of hydrolysis degree, film
      thickness and drug loading dose on in vitro drug release from the films were also
      investigated. In vitro swelling study showed that the swelling of partially
      hydrolyzed EVA films was greater than the EVA film and the film with higher
      hydrolysis degree swelled more intensively. X-ray diffraction (XRD) results
      exhibited that the crystallinity of the polymer increased with increasing
      hydrolysis degree. In paclitaxel-loaded EVA film, a part of paclitaxel was in
      crystalline form; while in paclitaxel-loaded partially hydrolyzed EVA films,
      paclitaxel was distributed in amorphous form or molecularly dispersed. In the in
      vitro drug release test, the film with higher hydrolysis degree and smaller
      thickness released paclitaxel more quickly. With higher drug loading dose, the
      drug release rate was larger. The partially hydrolyzed EVA films were applied for
      drug delivery systems for the first time, and demonstrated to have great
      capability of controlling drug release thanks to the adjustable hydrolysis
      degree.

PMID- 20804835
TI  - Wheat germ agglutinin-conjugated PLGA nanoparticles for enhanced intracellular
      delivery of paclitaxel to colon cancer cells.
AB  - The purpose of this study was to investigate the potentiation of the anticancer
      activity and enhanced cellular retention of paclitaxel-loaded PLGA nanoparticles
      after surface conjugation with wheat germ agglutinin (WGA) against colon cancer
      cells. Glycosylation patterns of representative colon cancer cells confirmed the
      higher expression levels of WGA-binding glycoproteins in the Caco-2 and HT-29
      cells, than in the CCD-18Co cells. Cellular uptake and in vitro cytotoxicity of
      WNP (final formulation) against colon cell lines was evaluated alongside control
      formulations. Confocal microscopy and quantitative analysis of intracellular
      paclitaxel were used to monitor the endocytosis and retention of nanoparticles
      inside the cells. WNP showed enhanced anti-proliferative activity against Caco-2
      and HT-29 cells compared to corresponding nanoparticles without WGA conjugation
      (PNP). The greater efficacy of WNP was associated with higher cellular uptake and
      sustained intracellular retention of paclitaxel, which in turn was attributed to
      the over-expression of N-acetyl-D-glucosamine-containing glycoprotein on the
      colon cell membrane. WNP also demonstrated increased intracellular retention in
      the Caco-2 (30% of uptake) and HT-29 (40% of uptake) cells, following post-uptake
      incubation with fresh medium, compared to the unconjugated PNP nanoparticles (18%
      in Caco-2) and (27% in HT-29), respectively. Cellular trafficking study of WNP
      showed endocytosed WNP could successful escape from the endo-lysosome compartment
      and release into the cytosol with increasing incubation time. It may be concluded
      that WNP has the potential to be applied as a targeted delivery platform for
      paclitaxel in the treatment of colon cancer.

PMID- 20804836
TI  - The origin and evolution of high-frequency hearing in (most) mammals.

PMID- 20804837
TI  - Pu-erh tea tasting in Yunnan, China: correlation of drinkers' perceptions to
      phytochemistry.
AB  - AIM OF THE STUDY: Pu-erh (or pu'er) tea tasting is a social practice that
      emphasizes shared sensory experience, wellbeing, and alertness. The present study
      examines how variable production and preparation practices of pu-erh tea affect
      drinkers' perceptions, phytochemical profiles, and anti-oxidant activity.
      MATERIALS AND METHODS: One hundred semi-structured interviews were conducted in
      Yunnan Province to understand the cultural and environmental context of pu-erh
      tea tasting. The gong fu cha dao ('way of tea' with 'effort,' 'work,' or 'skill')
      method of brewing tea through multiple infusions was employed to evaluate green
      and black pu-erh samples from smallholder agro-forests and terrace plantations.
      Ranking interviews, High Performance Liquid Chromatography (HPLC), and the 1-1
      diphenyl-2-picrylhydrazyl (DPPH) assay were conducted to characterize color and
      taste profiles, Total Catechin Content (TCC), Total Methylxanthine Content (TMC),
      and free radical scavenging capacity (IC(50)). RESULTS: Significant variation was
      found among pu-erh samples based on: (1) agro-ecosystem mode of production by TCC
      (P<0.0001) and TMC (P<0.0265), (2) processing method for TCC (P<0.0001), TMC
      (P<0.0027), and free radical scavenging capacity (P<0.0001), (3) infusion
      sequence for TMC (P<0.0013), (4) taste rankings for TCC (P<0.0001), TMC
      (P<0.0001), and IC(50) (P<0.0059) and, (5) color rankings for TMC (P<0.0009) and
      IC(50) (P<0.0001). Samples rated as bitter and bitter-sweet contained the
      greatest TCC and free radical scavenging capacity. CONCLUSIONS: This research
      demonstrated that production environment, processing methods, and infusion
      sequence in preparing tea are related to the phytochemical profile, free radical
      scavenging activity, and flavor of tea. Findings contribute to the ethnomedical
      literature by supporting previous studies that have hypothesized that the taste
      of plants, particularly bitterness, may guide societies in the search for
      medicinal plants and beneficial phytochemicals.

PMID- 20804838
TI  - Hypnotic effects and binding studies for GABA(A) and 5-HT(2C) receptors of
      traditional medicinal plants used in Asia for insomnia.
AB  - AIM OF THE STUDY: Many medicinal plants have been used for treatment of insomnia
      in Asia. However, scientific evidence and precise mechanism for their sedative
      hypnotic activity have not been fully investigated. Thus, we investigated the
      binding activity of the oriental plant extracts (mainly from Korea and Japan) to
      the well-known molecular targets for sleep regulation, GABA(A) and 5-HT(2C)
      receptors. Following the binding assay, sedative-hypnotic effects of the extracts
      with high affinity were examined in an animal model of sleep. MATERIALS AND
      METHODS: Aqueous and ethanol extracts of 15 medicinal plants were tested for
      binding at the benzodiazepine site of GABA(A) receptor and 5-HT site of 5-HT(2C)
      receptor. The sedative-hypnotic effects of selected extracts were evaluated by
      measuring the sleep latency and sleep duration during pentobarbital-induced sleep
      in mice after oral administration of extracts. RESULTS: In the GABA(A) assay, the
      ethanol extracts of licorice and danshen displayed concentration-dependent, high
      affinity binding, whereas in the 5-HT(2C) assay, the ethanol extracts of ginseng
      and silk tree showed high affinity. Among these extracts we tested previously
      uncharacterized licorice and silk tree for hypnotic effects. We found the ethanol
      extracts of licorice and silk tree significantly decreased sleep latency and
      increased sleep duration in pentobarbital-induced sleep. CONCLUSIONS: We
      demonstrate for the first time that licorice and silk tree have the sedative
      hypnotic activity possibly by modulating GABA(A) and 5-HT(2C) receptors. We
      propose that licorice and silk tree might be effective candidates for treatment
      of insomnia.

PMID- 20804839
TI  - Biological activities and safety of Thanaka (Hesperethusa crenulata) stem bark.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The stem bark powder of Hesperethusa crenulata or
      Thanaka has been used on the face by Myanmar women for more than a thousand years
      as a skin care regiment. AIM OF THE STUDY: The aim of the current study was to
      both verify the safety and evaluate some biological activities of the Thanaka
      bark. MATERIALS AND METHODS: Maceration of the Thanaka bark powder resulted in
      hexane, dichloromethane, ethyl acetate, methanol, 85% ethanol and water extracts.
      For the safety evaluation, cytotoxicity and genotoxicity of each extract were
      tested. Antibacterial, tyrosinase inhibition, antioxidant and anti-inflammatory
      activities were evaluated for each extract. RESULTS AND CONCLUSIONS: Extracts
      from Thanaka bark showed strong anti-inflammatory, significant antioxidation,
      mild tyrosinase inhibition and slight antibacterial activities. All extracts and
      the original bark powder showed no detectable genotoxicity while very low
      cytotoxicity with IC(50) value of more than 12 mg/ml was detected in the water
      extract. Thus, the use of the Thanaka bark in the form of a watery paste as a
      skin care regiment is not only safe but also beneficial to skin.

PMID- 20804840
TI  - Inhibition of intestinal glucose absorption by anti-diabetic medicinal plants
      derived from the James Bay Cree traditional pharmacopeia.
AB  - BACKGROUND: Type II diabetes and obesity are major health problems worldwide and
      aboriginal peoples are particularly at risk. To address this problem in Canadian
      native populations who find modern pharmaceuticals culturally inappropriate, our
      team is testing the traditional pharmacopeia of the James Bay Cree for anti
      diabetic and anti-obesity activities. More specifically, the aim of the present
      study was to define the effects of traditional plants on intestinal glucose
      absorption, an under-appreciated anti-hyperglycaemic and anti-obesity activity.
      METHODS: Crude ethanol extracts of 17 Boreal forest medicinal plants were tested
      in vitro using the Caco-2 human enterocytic cell line and in vivo using an oral
      glucose tolerance test. RESULTS: Thirteen of seventeen extracts were observed to
      significantly inhibit uptake when administered simultaneously with (3)H
      deoxyglucose. Inhibition was dose-dependent and, in a few cases, even surpassed
      that induced by a combination of the positive controls. To validate these effects
      in vivo, four plant extracts were administered by intragastric gavage at 250
      mg/kg to normal rats simultaneously with a 3g/kg bolus of glucose. This resulted
      in a decrease in peak glycaemia by approximately 40% for two of them. Similarly,
      only 2 extracts reduced glucose transport after long term incubation and this
      could be related to reductions in the expression of SGLT-1 or GLUT-2 proteins.
      CONCLUSIONS: These findings indicate that competitive inhibition of intestinal
      glucose uptake can be achieved by crude extracts of medicinal plants. Such
      extracts could be taken with meals to control postprandial glycaemia and reduce
      caloric intake in high risk populations that are positively inclined towards
      traditional medicine.

PMID- 20804841
TI  - The hippocampus of Ames dwarf mice exhibits enhanced antioxidative defenses
      following kainic acid-induced oxidative stress.
AB  - INTRODUCTION: The vulnerability of the hippocampus to the effects of aging has
      been found to be associated with a decline in growth hormone/insulin like growth
      factor-1 (GH/IGF-1), and an increase in oxidative stress. We have evidence that
      long-living GH-deficient Ames dwarf mice have enhanced antioxidant protection in
      the periphery but the protection in the central nervous system is less clear.
      MATERIAL AND METHODS: In the present study, we evaluated the antioxidative
      defense enzyme status in the hippocampus of Ames dwarf and wild type mice at 3,
      12 and 24 months of age and examined the ability of each genotype to resist
      kainic acid-induced (KA) oxidative stress. An equiseizure concentration of KA was
      administered such that both genotypes responded with similar seizure scores and
      lipid peroxidation. RESULTS: We found that GH-sufficient wild type mice showed an
      increase in oxidative stress as indicated by the reduced ratio of glutathione:
      glutathione disulfide following KA injection while this ratio was maintained in
      GH-deficient Ames dwarf mice. In addition, glutathione peroxidase activity (GPx)
      as well as GPx1 mRNA expression was enhanced in KA-injected Ames dwarf mice but
      decreased in wild type mice. There was no induction of Nrf-2 (an oxidative stress
      induced transcription factor) gene expression in Ames dwarf mice following KA
      further suggesting maintenance of antioxidant defense in GH-deficiency under
      oxidative stress conditions. DISCUSSION: Therefore, based on equiseizure
      administration of KA, Ames dwarf mice have an enhanced antioxidant defense
      capacity in the hippocampus similar to that observed in the periphery. This
      improved defense capability in the brain is likely due to increased GPx
      availability in Ames mice and may contribute to their enhanced longevity.

PMID- 20804842
TI  - Defects in cytokine-mediated neuroprotective glial responses to excitotoxic
      hippocampal injury in senescence-accelerated mouse.
AB  - Aging is a result of damage accumulation, and understanding of the mechanisms of
      aging requires exploration of the cellular and molecular systems functioning to
      control damage. Senescence-accelerated mouse prone 10 (SAMP10) has been
      established as an inbred strain exhibiting accelerated aging with an earlier
      onset of cognitive impairment due to neurodegeneration than the senescence
      resistant control (SAMR1) strain. We hypothesized that tissue-protective
      responses of glial cells are impaired in SAMP10 mice. We injected kainic acid
      (KA) to induce hippocampal injury and studied how cytokines were upregulated on
      Day 3 using 3-month-old SAMP10 and SAMR1 mice. Following microarray-based
      screening for upregulated genes, we performed real-time RT-PCR and
      immunohistochemistry. Results indicated well-orchestrated cytokine-mediated glial
      interactions in the injured hippocampus of SAMR1 mice, in which microglia-derived
      interferon (IFN)-gamma stimulated astrocytes via IFN-gamma receptor and thereby
      induced expression of CXCL10 and macrophage inflammatory protein (MIP)-1alpha,
      and activated microglia produced granulocyte-macrophage colony-stimulating factor
      (GM-CSF) and osteopontin (OPN). OPN was the most strongly upregulated cytokine.
      CD44, an OPN receptor, was also strongly upregulated in the neuropil, especially
      on neurons and astrocytes. KA-induced hippocampal upregulation of these cytokines
      was strikingly reduced in SAMP10 mice compared to SAMR1 mice. On Day 30 after KA
      injection, SAMP10 but not SAMR1 mice exhibited hippocampal layer atrophy. Since
      the OPN-CD44 system is essential for neuroprotection and remodeling, these
      findings highlight the defects of SAMP10 mice in cytokine-mediated
      neuroprotective glia-neuron interactions, which may be associated with the
      mechanism underlying the vulnerability of SAMP10 mice to age-related
      neurodegeneration.

PMID- 20804843
TI  - Calpain inhibitors reduce retinal hypoxia in ischemic retinopathy by improving
      neovascular architecture and functional perfusion.
AB  - In ischemic retinopathies, underlying hypoxia drives abnormal neovascularization
      that damages retina and causes blindness. The abnormal neovasculature is tortuous
      and leaky and fails to alleviate hypoxia, resulting in more pathological
      neovascularization and retinal damage. With an established model of ischemic
      retinopathy we found that calpain inhibitors, when administered in moderation,
      reduced architectural abnormalities, reduced vascular leakage, and most
      importantly reduced retinal hypoxia. Mechanistically, these calpain inhibitors
      improved stability and organization of the actin cytoskeleton in retinal
      endothelial cells undergoing capillary morphogenesis in vitro, and they similarly
      improved organization of actin cables within new blood vessels in vivo. Hypoxia
      induced calpain activity in retinal endothelial cells and severely disrupted the
      actin cytoskeleton, whereas calpain inhibitors preserved actin cables under
      hypoxic conditions. Collectively, these findings support the hypothesis that
      hyper-activation of calpains by hypoxia contributes to disruption of the retinal
      endothelial cell cytoskeleton, resulting in formation of neovessels that are
      defective both architecturally and functionally. Modest suppression of calpain
      activity with calpain inhibitors restores cytoskeletal architecture and promotes
      formation of a functional neovasculature, thereby reducing underlying hypoxia. In
      sharp contrast to "anti-angiogenesis" strategies that cannot restore normoxia and
      may aggravate hypoxia, the therapeutic strategy described here does not inhibit
      neovascularization. Instead, by improving the function of neovascularization to
      reduce underlying hypoxia, moderate calpain inhibition offers a method for
      alleviating retinal ischemia, thereby suggesting a new treatment paradigm based
      on improvement rather than inhibition of new blood vessel growth.

PMID- 20804845
TI  - T cell diversity and TcR repertoires in teleost fish.
AB  - In vertebrates, the diverse and extended range of antigenic motifs is matched to
      large populations of lymphocytes. The concept of immune repertoire was proposed
      to describe this diversity of lymphocyte receptors--IG and TR--required for the
      recognition specificity. Immune repertoires have become useful tools to describe
      lymphocyte and receptor populations during the immune system development and in
      pathological situations. In teleosts, the presence of conventional T cells was
      first proposed to explain graft rejection and optimized specific antibody
      production. The discovery of TR genes definitely established the reality of
      conventional T cells in fish. The development of genomic and EST databases
      recently led to the description of several key T cell markers including CD4, CD8,
      CD3, CD28, CTLA4, as well as important cytokines, suggesting the existence of
      different T helper (Th) subtypes, similar to the mammalian Th1, Th2 and Th17.
      Over the last decade, repertoire studies have demonstrated that both public and
      private responses occur in fish as they do in mammals, and in vitro specific
      cytotoxicity assays have been established. While such typical features of T cells
      are similar in both fish and mammals, the structure of particular repertoires
      such as the one of gut intra-epithelial lymphocytes seems to be very different.
      Future studies will further reveal the particular characteristics of teleost T
      cell repertoires and adaptive responses.

PMID- 20804844
TI  - Hair and skin sterols in normal mice and those with deficient dehydrosterol
      reductase (DHCR7), the enzyme associated with Smith-Lemli-Opitz syndrome.
AB  - Our recent studies have focused on cholesterol synthesis in mouse models for 7
      dehydrosterolreductase (DHCR7) deficiency, also known as Smith-Lemli-Opitz
      syndrome. Investigations of such mutants have relied on tissue and blood levels
      of the cholesterol precursor 7-dehydrocholesterol (7DHC) and its 8-dehydro
      isomer. In this investigation by gas chromatography/mass spectrometry (GC/MS) we
      have identified and quantified cholesterol and its precursors (7DHC, desmosterol,
      lathosterol, lanosterol and cholest-7,24-dien-3beta-ol) in mouse hair. The
      components were characterized and their concentrations were compared to those
      found in mouse skin and serum. Hair appeared unique in that desmosterol was a
      major sterol component, almost matching in concentration cholesterol itself. In
      DHCR7 deficient mice, dehydrodesmosterol (DHD) was the dominant hair Delta(7)
      sterol. Mutant mouse hair had much higher concentrations of 7-dehydrosterols
      relative to cholesterol than did serum or tissue at all ages studied. The 7DHC/C
      ratio in hair was typically about sevenfold the value in serum or skin and the
      DHD/D ratio was 100* that of the serum 7DHC/C ratio. Mutant mice compensate for
      their DHCR7 deficiency with maturity, and the tissue and blood 7DHC/C become
      close to normal. That hair retains high relative concentrations of the dehydro
      precursors suggests that the apparent up-regulation of Dhcr7 seen in liver is
      slower to develop at the site of hair cholesterol synthesis.

PMID- 20804846
TI  - Effects of transcranial magnetic stimulation on visual evoked potentials in a
      visual suppression task.
AB  - Transcranial magnetic stimulation (TMS) can non-invasively modify cortical neural
      activity by means of a time-varying magnetic field. For example, in cognitive
      neuroscience, it is applied to create reversible "virtual lesions" in healthy
      humans (usually assessed as diminished performance in a behavioral task), thereby
      helping to establish causal structure-function relationships. Despite its
      widespread use, it is still rather unclear how TMS acts on existing, task-related
      neural activity, potentially resulting in a measurable effect on the behavioral
      level. Here, we deliver TMS to early visual areas while recording EEG in order to
      directly characterize the interaction between TMS-evoked (TEPs) and visual-evoked
      potentials (VEPs). Simultaneously, the subjects' performance is assessed in a
      visual forced-choice task. This allows us to compare the TMS effects on the VEPs
      across different levels of behavioral impairment. By systematically varying the
      stimulation intensity, we demonstrate that TMS strongly enhances the overall
      visual stimulus-related activity (rather than disrupting it). This enhancement
      effect saturates when behavior is impaired. This might indicate that the neural
      coding of the visual stimulus is robust to noise within a certain dynamic range
      (as indexed by the enhancement). Strong disturbances might saturate this range,
      causing behavioral impairment. Variation of the timing between the visual
      stimulus and the magnetic pulse reveals a "constructive interference" between the
      TEPs and VEPs: The better the overlap between both evoked potentials, the
      stronger the interaction effect when TMS and visual stimulation are combined.
      Importantly, however, this effect is uncorrelated with the strength of behavioral
      impairment.

PMID- 20804848
TI  - Consumption of caloric and non-caloric versions of a soft drink differentially
      affects brain activation during tasting.
AB  - Sensory-specific satiety, which is defined as a relative decrease in
      pleasantness, is increased by greater oro-sensory stimulation. Both sensory
      specific satiety and pleasantness affect taste activation in the orbitofrontal
      cortex. In contrast, metabolic satiety, which results from energy intake, is
      expected to modulate taste activation in reward areas. The aim of this study was
      to determine the effects of the amount of oro-sensory stimulation and energy
      content on consumption-induced changes in taste activation. Ten men participated
      in a 2*2 randomized crossover study. Subjects were scanned twice using functional
      magnetic resonance imaging: after fasting for at least 2h and after treatment, on
      four occasions. Treatment consisted of the ingestion of 450 mL of orangeade
      (sweetened with 10% sucrose or non-caloric sweeteners) at 150 mL/min, with either
      small (5 mL) or large (20 mL) sips. During scanning, subjects alternately tasted
      orangeade, milk and tomato juice and rated its pleasantness. Before and after the
      scans, subjects rated pleasantness, prospective consumption, desire to eat and
      sweetness for all tastants. Main findings were that, before treatment, the
      amygdala was activated more by non-caloric than by caloric orangeade. Caloric
      orangeade activated part of the striatum before, but not after treatment. We
      observed no main effects of sip size on taste activation and no interaction
      between sip size and caloric content. In conclusion, the brain responds
      differentially to caloric and non-caloric versions of a sweet drink and
      consumption of calories can modulate taste activation in the striatum. Further
      research is needed to confirm that the observed differences are due to caloric
      content and not to (subliminal) differences in the sensory profile. In addition,
      implications for the effectiveness of non-caloric sweeteners in decreasing energy
      intake need to be established.

PMID- 20804847
TI  - Age-related differences in white matter integrity and cognitive function are
      related to APOE status.
AB  - While an extensive literature is now available on age-related differences in
      white matter integrity measured by diffusion MRI, relatively little is known
      about the relationships between diffusion and cognitive functions in older
      adults. Even less is known about whether these relationships are influenced by
      the apolipoprotein (APOE) epsilon4 allele, despite growing evidence that epsilon4
      increases cognitive impairment in older adults. The purpose of the present study
      was to examine these relationships in a group of community-dwelling cognitively
      normal older adults. Data were obtained from a sample of 126 individuals (ages 52
      92) that included 32 epsilon4 heterozygotes, 6 epsilon4 homozygotes, and 88
      noncarriers. Two measures of diffusion, the apparent diffusion coefficient (ADC)
      and fractional anisotropy (FA), were obtained from six brain regions-frontal
      white matter, lateral parietal white matter, the centrum semiovale, the genu and
      splenium of the corpus callosum, and the temporal stem white matter-and were used
      to predict composite scores of cognitive function in two domains, executive
      function and memory function. Results indicated that ADC and FA differed with
      increasing age in all six brain regions, and these differences were significantly
      greater for epsilon4 carriers compared to noncarriers. Importantly, after
      controlling for age, diffusion measures predicted cognitive function in a region
      specific way that was also influenced by epsilon4 status. Regardless of APOE
      status, frontal ADC and FA independently predicted executive function scores for
      all participants, while temporal lobe ADC additionally predicted executive
      function for epsilon4 carriers but not noncarriers. Memory scores were predicted
      by temporal lobe ADC but not frontal diffusion for all participants, and this
      relationship was significantly stronger in epsilon4 carriers compared to
      noncarriers. Taken together, age and temporal lobe ADC accounted for a striking
      53% of the variance in memory scores within the epsilon4 carrier group. The
      results provide further evidence that APOE epsilon4 has a significant impact on
      the trajectory of age-related cognitive functioning in older adults. Possible
      mechanisms are discussed that could account for the associations between
      epsilon4, diffusion, and cognitive function, including the influence of epsilon4
      on neural repair, oxidative stress, and the health of myelin-producing
      oligodendroglia.

PMID- 20804849
TI  - Imaging separation of neuronal from vascular effects of cocaine on rat cortical
      brain in vivo.
AB  - MRI techniques to study brain function assume coupling between neuronal activity,
      metabolism and flow. However, recent evidence of physiological uncoupling between
      neuronal and cerebrovascular events highlights the need for methods to
      simultaneously measure these three properties. We report a multimodality optical
      approach that integrates dual-wavelength laser speckle imaging (measures changes
      in blood flow, blood volume and hemoglobin oxygenation), digital-frequency
      ramping optical coherence tomography (images quantitative 3D vascular network)
      and Rhod(2) fluorescence (images intracellular calcium for measure of neuronal
      activity) at high spatiotemporal resolutions (30 MUm, 10 Hz) and over a large
      field of view (3*5 mm(2)). We apply it to assess cocaine's effects in rat
      cortical brain and show an immediate decrease (3.5+/-0.9 min, phase 1) in the
      oxygen content of hemoglobin and the cerebral blood flow followed by an overshoot
      (7.1+/-0.2 min, phase 2) lasting over 20 min whereas Ca(2+) increased immediately
      (peaked at t=4.1+/-0.4 min) and remained elevated. This enabled us to identify a
      delay (2.9+/-0.5 min) between peak neuronal and vascular responses in phase 2.
      The ability of this multimodality optical approach for simultaneous imaging at
      high spatiotemporal resolutions permits us to distinguish the vascular versus
      cellular changes of the brain, thus complimenting other neuroimaging modalities
      for brain functional studies (e. g., PET, fMRI).

PMID- 20804850
TI  - Effects of physiological noise in population analysis of diffusion tensor MRI
      data.
AB  - The goal of this study is to characterize the potential effect of artifacts
      originating from physiological noise on statistical analysis of diffusion tensor
      MRI (DTI) data in a population. DTI derived quantities including mean diffusivity
      (Trace(D)), fractional anisotropy (FA), and principal eigenvector (epsilon(1))
      are computed in the brain of 40 healthy subjects from tensors estimated using two
      different methods: conventional nonlinear least-squares, and robust fitting
      (RESTORE). RESTORE identifies artifactual data points as outliers and excludes
      them on a voxel-by-voxel basis. We found that outlier data points are localized
      in specific spatial clusters in the population, indicating a consistency in brain
      regions affected across subjects. In brain parenchyma RESTORE slightly reduces
      inter-subject variance of FA and Trace(D). The dominant effect of artifacts,
      however, is bias. Voxel-wise analysis indicates that inclusion of outlier data
      points results in clusters of under- and over-estimation of FA, while Trace(D) is
      always over-estimated. Removing outliers affects epsilon(1) mostly in low
      anisotropy regions. It was found that brain regions known to be affected by
      cardiac pulsation - cerebellum and genu of the corpus callosum, as well as
      regions not previously reported, splenium of the corpus callosum-show significant
      effects in the population analysis. It is generally assumed that statistical
      properties of DTI data are homogenous across the brain. This assumption does not
      appear to be valid based on these results. The use of RESTORE can lead to a more
      accurate evaluation of a population, and help reduce spurious findings that may
      occur due to artifacts in DTI data.

PMID- 20804851
TI  - Mapping plasticity in the forepaw digit barrel subfield of rat brains using
      functional MRI.
AB  - The topographic organization of the forepaw barrel subfield in layer IV of rat
      primary somatosensory cortex (S1) is a good model for studying neural function
      and plasticity. The goal of this study was to test the feasibility of functional
      MRI (fMRI) to map the forepaw digit representations in the S1 of the rat and its
      plasticity after digit amputation. Three dimensional echo-planar imaging with 300
      micron isotropic resolution at 11.7 T was used to achieve high signal-to-noise
      ratios and laminar layer resolution. By alternating electrical stimulation of the
      2nd (D2) and 4th (D4) digits, functional activation in layer IV of the barrel
      subfields could be distinguished using a differential analysis. Furthermore, 2
      and a half months after the amputation of the 3rd digit in baby rats, the
      overlapping area between D2 and D4 representations was increased. This indicates
      that the forepaw barrel subfield previously associated with the ablated digit is
      now associated with the representation of nearby digits, which is consistent with
      studies using electrophysiology and cytochrome oxidase staining.

PMID- 20804852
TI  - Extended unified SEM approach for modeling event-related fMRI data.
AB  - There has been increasing emphasis in fMRI research on the examination of how
      regions covary in a distributed neural network. Event-related data designs
      present a unique challenge to modeling how couplings among regions change in the
      presence of experimental manipulations. The present paper presents the extended
      unified SEM (euSEM), a novel approach for acquiring effective connectivity maps
      with event-related data. The euSEM adds to the unified SEM, which models both
      lagged and contemporaneous effects, by estimating the direct effects that
      experimental manipulations have on blood-oxygen-level dependent activity as well
      as the modulating effects the manipulations have on couplings among regions.
      Monte Carlos simulations included in this paper offer support for the model's
      ability to recover covariance patterns used to estimate data. Next, we apply the
      model to empirical data to demonstrate feasibility. Finally, the results of the
      empirical data are compared to those found using dynamic causal modeling. The
      euSEM provides a flexible approach for modeling event-related data as it may be
      employed in an exploratory, partially exploratory, or entirely confirmatory
      manner.

PMID- 20804853
TI  - Adaptation to intermittent hypoxia restricts nitric oxide overproduction and
      prevents beta-amyloid toxicity in rat brain.
AB  - This study tested the hypothesis that adaptation to intermittent hypoxia (AIH)
      can prevent overproduction of nitric oxide (NO) in brain and neurodegeneration
      induced by beta-amyloid (Abeta) toxicity. Rats were injected with a Abeta protein
      fragment (25-35) into the nucleus basalis magnocellularis. AIH (simulated
      altitude of 4000 m, 14 days, 4h daily) was produced prior to the Abeta injection.
      A passive, shock-avoidance, conditioned response test was used to evaluate memory
      function. Degenerating neurons were visualized in stained cortical sections. NO
      production was evaluated in brain tissue by the content of nitrite and nitrate.
      Expression of nNOS, iNOS, and eNOS was measured in the cortex and the hippocampus
      using Western blot analysis. 3-Nitrotyrosine formation, a marker of protein
      nitration, was quantified by slot blot analysis. Abeta injection impaired memory
      of rats; AIH significantly alleviated this disorder. Histological examination
      confirmed the protective effect of AIH. Degenerating neurons, which were numerous
      in the cortex of Abeta-injected, unadapted rats, were essentially absent in the
      brain of hypoxia-adapted rats. Injections of Abeta resulted in significant
      increases in NOx and in expression of all NOS isoforms in brain; AIH blunted
      these increases. NO overproduction was associated with increased amounts of 3
      nitrotyrosine in the cortex and hippocampus. AIH alone did not significantly
      influence tissue 3-nitrotyrosine, but significantly restricted its increase after
      the Abeta injection. Therefore, AIH affords significant protection against
      experimental Alzheimer's disease, and this protection correlates with restricted
      NO overproduction.

PMID- 20804854
TI  - Hemodynamic effects of inducible nitric oxide synthase inhibition combined with
      sildenafil during acute pulmonary embolism.
AB  - While endogenous nitric oxide (NO) may be relevant to the beneficial hemodynamic
      effects produced by sildenafil during acute pulmonary embolism (APE), huge
      amounts of inducible NO synthase (iNOS)-derived NO may contribute to lung injury.
      We hypothesized that iNOS inhibition with S-methylisothiourea could attenuate APE
      induced increases in oxidative stress and pulmonary hypertension and, therefore,
      could improve the beneficial hemodynamic and antioxidant effects produced by
      sildenafil during APE. Hemodynamic evaluations were performed in non-embolized
      dogs treated with saline (n=4), S-methylisothiourea (0.01 mg/kg followed by 0.5
      mg/kg/h, n=4), sildenafil (0.3 mg/kg, n=4), or S-methylisothiourea followed by
      sildenafil (n=4), and in dogs that received the same drugs and were embolized
      with silicon microspheres (n=8 for each group). Plasma nitrite/nitrate (NOx) and
      thiobarbituric acid reactive substances (TBARS) concentrations were determined by
      Griess and a fluorometric assay, respectively. APE increased mean pulmonary
      arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) by 25+/
      1.7 mm Hg and by 941+/-34 dyn s cm(-5) m(-2), respectively. S-methylisothiourea
      neither attenuated APE-induced pulmonary hypertension, nor enhanced the
      beneficial hemodynamic effects produced by sildenafil after APE (>50% reduction
      in pulmonary vascular resistance). While sildenafil produced no change in plasma
      NOx concentrations, S-methylisothiourea alone or combined with sildenafil blunted
      APE-induced increases in NOx concentrations. Both drugs, either alone or
      combined, produced antioxidant effects. In conclusion, although iNOS-derived NO
      may play a key role in APE-induced oxidative stress, our results suggest that the
      iNOS inhibitor S-methylisothiourea neither attenuates APE-induced pulmonary
      hypertension, nor enhances the beneficial hemodynamic effects produced by
      sildenafil.

PMID- 20804855
TI  - Evaluation of the antigenicity of universal epitopes from PvDBPII in individuals
      exposed to Plasmodium vivax malaria.
AB  - The Duffy-binding protein (PvDBP) mediates invasion of reticulocytes by the
      malaria parasite Plasmodium vivax. PvDBP has been recognized as a good vaccine
      candidate due to its ability to induce antibody responses capable of inhibiting
      target cell invasion after natural infections. For the development of subunit
      based vaccines, it is important to identify universal epitopes that could be
      presented by different HLA-DR alleles to induce effective cellular and humoral
      immune responses. In this study, the antigenicity of universal epitopes from
      PvDBPII was evaluated by stimulating peripheral blood mononuclear cells (PBMCs)
      isolated from individuals with different degrees of P. vivax malaria exposure and
      distinct HLA-DR alleles. Peptides 1635 and 1638 induced lymphoproliferation and
      stimulated the production of IL-6 and IFN-gamma. The results suggest that
      conserved peptides binding with high activity to red blood cells and with known
      affinity to HLA-DR proteins could be good components for a P. vivax vaccine.

PMID- 20804857
TI  - The HMGB protein gene family in zebrafish: Evolution and embryonic expression
      patterns.
AB  - The High-Mobility Group Box (HMGB) proteins are highly abundant proteins with
      both nuclear and extracellular roles in key biological processes. In mammals,
      three family members are present: HMGB1, HMGB2 and HMGB3. We characterized the
      HMGB family in zebrafish and report a detailed phylogenetic analysis of HMGB
      proteins. The B1, B2, and B3 subfamilies are present in cartilaginous fish, bony
      fish, and tetrapods, while jawless fish sequences emerge as basal to the gene
      family expansion. Two co-orthologs of each mammalian HMGB gene are present in
      zebrafish. All six zebrafish hmgb genes are maternally expressed, but huge
      differences in expression levels exist during embryonic development. The
      hmgb2a/hmgb2b genes are the most highly expressed, while hmgb3b is expressed at
      the lowest level. Remarkably, hmgb3 genes are not present in fugu, medaka,
      Tetraodon and stickleback. Our analysis highlights substantial overlaps, but also
      subtle differences and specificities in the expression patterns of the zebrafish
      hmgb genes.

PMID- 20804856
TI  - Sero-epidemiological survey of gnathostomiasis in Lao PDR.
AB  - While human gnathostomiasis cases have been reported sporadically in Lao PDR
      since 1975, little is known about the disease in this country. We aimed to
      investigate sero-prevalence of gnathostomiasis and Gnathostoma species in Lao
      PDR. One village each in the north, central and south regions of Lao PDR was
      selected as the study sites. Overall, 125 (29.8%) of 420 sera from the randomly
      selected participants were sero-positive by immunoblot technique, with anti
      Gnathostoma IgG antibody against the 24 kDa fraction. The sero-prevalence was
      high in the central (47.1%) and south (38.6%), but low (3.6%) in the north. Risk
      factor analyses revealed that the consumption of raw/undercooked fish was
      significantly associated with Gnathostoma sero-positivity (95% CI 1.05-17.05,
      P=0.042). The sero-positivity significantly increased with the age of the
      participants. Several fish, swamp eels, and frogs collected from central and
      southern Lao were infected with G. spinigerum advanced 3rd-stage larvae. Channa
      limbata (red-tailed snakehead fish) was identified as a natural second
      intermediate host of G. spinigerum. Eggs of G. spinigerum were found in dog feces
      collected in the south. Gnathostomiasis is endemic in central and southern Laos,
      so that preventive measures should be introduced for people living in these
      regions.

PMID- 20804858
TI  - Identification of adult midgut precursors in Drosophila.
AB  - The adult Drosophila midgut is thought to arise from an endodermal rudiment
      specified during embryogenesis. Previous studies have reported the presence of
      individual cells termed adult midgut precursors (AMPs) as well as "midgut
      islands" or "islets" in embryonic and larval midgut tissue. Yet the precise
      relationship between progenitor cell populations and the cells of the adult
      midgut has not been characterized. Using a combination of molecular markers and
      directed cell lineage tracing, we provide evidence that the adult midgut arises
      from a molecularly distinct population of single cells present by the
      embryonic/larval transition. AMPs reside in a distinct basal position in the
      larval midgut where they remain through all subsequent larval and pupal stages
      and into adulthood. At least five phases of AMP activity are associated with the
      stepwise process of midgut formation. Our data shows that during larval stages
      AMPs give rise to the presumptive adult epithelium; during pupal stages AMPs
      contribute to the final size, cell number and form. Finally, a genetic screen has
      led to the identification of the Ecdysone receptor as a regulator of AMP
      expansion.

PMID- 20804859
TI  - Is the population genetic structure of complex life cycle parasites determined by
      the geographic range of the most motile host?
AB  - Due to their particular way of life, dispersal of parasites is often mediated by
      their host's biology. Dispersal distance is relevant for parasites because high
      degree of dispersal leads to high gene flow, which counters the rate of parasite
      local adaptation in the host populations. Parasites with complex life cycles need
      to exploit sequentially more than one host species to complete their life cycle.
      Most trematode parasites have such complex life cycles involving invertebrate and
      vertebrate hosts. The spatial scales of invertebrate and vertebrate host
      populations are often different, which may decrease the probability that the
      parasite cycles locally in the intermediate host population. We used neutral
      microsatellite markers to determine genetic structure in Diplostomum
      pseudospathaceum parasites collected from local populations of freshwater snails
      (Lymnaea stagnalis). D. pseudospathaceum is a trematode that has two intermediate
      hosts (snail and fish) and a highly motile definitive host (bird). We found that
      the parasite population infecting the local snail populations showed no genetic
      structure over a large geographic range (over 300km). We also did not detect
      evidence for isolation by distance in the parasite. We conclude that dispersal in
      the motile definitive host is likely to prevent emergence of local population
      genetic structure in the parasite. Our results suggest that parasite dispersal in
      the definitive host may limit local cycling of the parasites in the intermediate
      host populations.

PMID- 20804860
TI  - Comparing metabolic network models based on genomic and automatically inferred
      enzyme information from Plasmodium and its human host to define drug targets in
      silico.
AB  - Plasmodium falciparum causes the most severe malaria pathogen and has developed
      resistance to existing drugs making it indispensable to discover new drugs. In
      order to predict drug targets in silico, a useful model for the metabolism is
      needed. However, automatically reconstructed network models typically cover more
      non-confirmed enzymes than confirmed enzymes of known gene products. Furthermore,
      it needs to be considered that the parasite takes advantage of the metabolism of
      the host. We compared several reconstructed network models and aimed to find the
      best suitable reconstruction for detecting drug targets in silico. We
      computationally reconstructed the metabolism based on automatically inferred
      enzymes and compared this with a reconstructed model that was based only on
      enzymes whose coding genes are known. Additionally, we tested if integrating
      enzymes of the host cell is beneficial for such an analysis. We employed several
      well established criteria for defining essential enzymes including chokepoints,
      betweenness centrality (or load-points), connectivity and the diameter of the
      networks. Comparing the modeling results with a comprehensive list of known drug
      targets for P. falciparum, showed that we had the best discovery success with a
      network model consisting only of enzymes from the parasite alone which coding
      genes were known.

PMID- 20804861
TI  - The administration of low doses of rituximab followed by hydroxychloroquine,
      prednisone and low doses of mycophenolate mofetil is an effective therapy in
      Latin American patients with active systemic lupus erythematosus.
AB  - BACKGROUND: In Latin America, the medical attention directed to systemic
      autoimmune diseases competes with a budget designed to fight poverty, lack of
      education, etc. In this context, the access to treatments recommended
      internationally are expensive and limited; therefore, research of methods that
      make these treatments cheaper is of paramount importance. OBJECTIVE: Our
      objective was to describe the 24-month clinical outcome of patients with active
      systemic lupus erythematosus (SLE) who received low doses of rituximab (RTX),
      followed by hydroxychloroquine (HCQ), prednisone and low doses of mycophenolate
      mofetil (MMF). METHODS: Forty-six patients with active SLE received 500 mg of RTX
      (together with 500 mg of methylprednisolone as a premedication) administered on
      two occasions 2 weeks apart, followed by HCQ (200-400 mg/day), prednisone and MMF
      (500-1000 mg/day) during a 24-month follow-up period. Clinical outcome was
      assessed using the MEX-SLE Disease Activity Index (MEX-SLEDAI) and serial
      serologic measurements. Remission was defined as MEX-SLEDAI scores 0-1, mild
      disease activity 2-5, moderate disease activity 6-9, severe 10-13, and very
      severe 14 or more. RESULTS: Disease activity decreased over time with treatment.
      At baseline, 19 (41.3%) patients had very severe, 16 (34.8%) severe, and 9
      (19.6%) moderate disease activity. Improvement on disease activity was detected
      at 3 months, since 9 (19.6%) patients reached disease remission after this period
      of time and remission increased to 16 (34.8%) patients at 6 months, 19 (41.3%) at
      1 year, and 23 (50%) at 2 years of follow-up (p<0.0001). CONCLUSION: The
      administration of low doses of RTX followed by HCQ, prednisone and low doses of
      MMF is an effective therapy in Latin American patients with active SLE.

PMID- 20804862
TI  - Mitochondrial oxidant stress increases PDE5 activity in persistent pulmonary
      hypertension of the newborn.
AB  - In the pulmonary vasculature, phosphodiesterase-5 (PDE5) degrades cGMP and
      inhibits nitric oxide-mediated, cGMP-dependent vasorelaxation. We previously
      reported that ventilation with 100% O2 increased PDE5 activity in pulmonary
      arteries (PAs) of pulmonary hypertension lambs (PPHN) more than in control lambs.
      In the present study, PA smooth muscle cells (PASMCs) from PPHN lambs had
      increased basal PDE5 activity, decreased cGMP-responsiveness to NO, and increased
      mitochondrial matrix oxidant stress compared to control PASMC. Hyperoxia (24 h)
      increased PDE5 activity and mitochondrial matrix oxidant stress above baseline to
      a similar degree in PPHN and control PASMC. Mitochondrially targeted catalase
      decreased PDE5 activity at baseline and after hyperoxia in PPHN PASMC. Similarly,
      catalase treatment of PPHN lambs ventilated with 100% O2 decreased PDE5 activity
      and increased cGMP in PA. We conclude that baseline PDE5 activity and oxidative
      stress is increased in PPHN PASMC, and scavenging H2O2 is sufficient to block
      oxidant-mediated increases in PDE5 activity in PPHN.

PMID- 20804863
TI  - Redox-control of matrix metalloproteinase-1: a critical link between free
      radicals, matrix remodeling and degenerative disease.
AB  - Many degenerative disease processes associated with aging result from enhanced
      extracellular matrix (ECM) breakdown. Concomitant with aberrant matrix
      destruction are alterations in levels of reactive oxygen species (ROS) generating
      and detoxification systems. ROS function as second messengers due to their
      ability to react with wide range of biomolecules resulting in modification of an
      array of signaling networks. ROS can activate upstream kinases (MKK) responsible
      for MAPK activation and restrict the activity of their inhibitory phosphatases.
      Here we focus on the redox-sensitive signaling components that control the
      expression of MMP-1, which is largely responsible for maintaining ECM
      homeostasis. Numerous disease processes are associated with shifts in steady
      state ROS levels that influence overall ECM degradation. This review highlights
      the redox-sensitive regulatory signals that control the expression of the primary
      initiating protease MMP-1 and provides strong rational for the use of antioxidant
      based therapies for treatment of degenerative disorders associated with aberrant
      matrix destruction.

PMID- 20804864
TI  - Intermittent hypoxia augments acute hypoxic sensing via HIF-mediated ROS.
AB  - Carotid bodies and neonatal adrenal medullary chromaffin cells (AMC) respond
      rapidly to acute hypoxia before compromising cellular functions. Responses to
      acute hypoxia are dynamically altered by chronic perturbations in arterial blood
      O2 levels resulting from breathing disorders. Sleep disordered breathing with
      recurrent apneas cause periodic decreases in arterial blood O2 or intermittent
      hypoxia (IH). Recent studies suggest that reactive oxygen species (ROS) mediate
      cellular adaptations to prolonged hypoxia. In this article we discuss the
      evidence for ROS in mediating exaggerated carotid body and AMC responses to acute
      hypoxia by IH and the underlying cellular and molecular mechanisms. IH increases
      ROS levels, and anti-oxidants prevent IH-induced augmented responses of the
      carotid body and AMC to hypoxia. The enhanced hypoxic sensitivity by IH involves
      ROS-dependent recruitment of transmitters/modulators in the carotid body and Ca2+
      signaling mechanisms in AMC. Mechanisms by which IH elevates ROS include
      activation of NADPH oxidases, inhibition of mitochondrial complex I activity and
      down-regulation of anti-oxidant enzymes. Transcriptional regulation of pro- and
      anti-oxidant enzymes by hypoxia-inducible factors 1 and 2 appears to be a major
      molecular mechanism regulating ROS generation by IH.

PMID- 20804866
TI  - Divergent roles of reactive oxygen species in the responses of perinatal adrenal
      chromaffin cells to hypoxic challenges.
AB  - The fetus and neonate experience variable patterns of low P(O)2(hypoxia) ranging
      from acute, sustained, and intermittent. Adaptation to hypoxia involves
      activation of key transcription factors, known as hypoxia-inducible factors (e.g.
      HIF-1alpha, HIF-2alpha), which regulate a number of genes in different cell
      types. This review focuses on the signaling pathways that mediate proper
      physiological responses of perinatal adrenomedullary chromaffin cells (AMC) to
      varying patterns of hypoxic challenges, and particularly on the controversial
      role of reactive oxygen species (ROS). At birth, acute hypoxia (seconds to
      minutes) directly stimulates catecholamine release from AMC via K+ channel
      inhibition, mediated by a decrease in mitochondrial-derived ROS. By contrast,
      exposure to chronic sustained hypoxia (CSH) induces HIF-2alpha in a fetal-derived
      chromaffin cell line independently of changes in ROS. Exposure to chronic
      intermittent hypoxia (CIH) activates antioxidant responses via the regulator Nrf
      2, in association with an increase in ROS and the induction of HIF-1alpha. We
      propose that the physiological responses of perinatal AMC to hypoxia and the
      ensuing directional changes in ROS are dependent on the pattern and duration of
      the hypoxic exposure.

PMID- 20804865
TI  - Mechanisms of sympathetic activation and blood pressure elevation by intermittent
      hypoxia.
AB  - Sleep disordered breathing with recurrent apneas is one of the most frequently
      encountered breathing disorder in adult humans and preterm infants. Recurrent
      apnea patients exhibit several co-morbidities including hypertension and
      persistent sympathetic activation. Intermittent hypoxia (IH) resulting from
      apneas appears to be the primary stimulus for evoking autonomic changes. The
      purpose of this article is to briefly review the effects of IH on chemo- and baro
      reflexes and circulating vasoactive hormones and their contribution to
      sympathetic activation and blood pressures. Sleep apnea patients and IH-treated
      rodents exhibit exaggerated arterial chemo-reflex. Studies on rodent models
      demonstrated that IH leads to hyperactive carotid body response to hypoxia. On
      the other hand, baro-reflex function is attenuated in patients with sleep apnea
      and in IH-treated rodents. Circulating vasoactive hormone levels are elevated in
      sleep apnea patients and in rodent models of IH. Thus, persistent sympathetic
      activation and hypertension associated with sleep apneas seems to be due to a
      combination of altered chemo- and baro-reflexes resulting in sympathetic
      activation and action of elevated circulating levels of vasoactive hormones on
      vasculature.

PMID- 20804867
TI  - Bone-implant interface strength and osseointegration: Biodegradable magnesium
      alloy versus standard titanium control.
AB  - Previous research on the feasibility of using biodegradable magnesium alloys for
      bone implant applications mainly focused on biocompatibility and corrosion
      resistance. However, successful clinical employment of endosseous implants is
      largely dependent on biological fixation and anchorage in host bone to withstand
      functional loading. In the present study, we therefore aimed to investigate
      whether bone-implant interface strength and osseointegration of a novel
      biodegradable magnesium alloy (Mg-Y-Nd-HRE, based on WE43) is comparable to that
      of a titanium control (Ti-6Al-7Nb) currently in clinical use. Biomechanical push
      out testing, microfocus computed tomography and scanning electron microscopy were
      performed in 72 Sprague-Dawley rats 4, 12 and 24 weeks after implantation to
      address this question. Additionally, blood smears were obtained from each rat at
      sacrifice to detect potential systemic inflammatory reactions. Push-out testing
      revealed highly significantly greater maximum push-out force, ultimate shear
      strength and energy absorption to failure in magnesium alloy rods than in
      titanium controls after each implantation period. Microfocus computed tomography
      showed significantly higher bone-implant contact and bone volume per tissue
      volume in magnesium alloy implants as well. Direct bone-implant contact was
      verified by histological examination. In addition, no systemic inflammatory
      reactions were observed in any of the animals. We conclude that the tested
      biodegradable implant is superior to the titanium control with respect to both
      bone-implant interface strength and osseointegration. These results suggest that
      the investigated biodegradable magnesium alloy not only achieves enhanced bone
      response but also excellent interfacial strength and thus fulfils two critical
      requirements for bone implant applications.

PMID- 20804869
TI  - Breast cancer mimicking fibroadenomas in postmenopausal women.
AB  - INTRODUCTION: Fibroadenomas (FADs) are benign breast lesions usually seen in late
      teens less so common in postmenopausal women. This is a case series of
      postmenopausal patients, where breast cancer looked like fibroadenoma on imaging.
      The aim of this study was to identify the important role of tissue diagnosis in
      FAD like lesions on imaging and highlight the deceiving imaging findings.
      MATERIALS AND METHODS: We retrospectively reviewed the medical records of
      patients at our Breast unit who were treated for breast cancer under one surgeon
      in the period of Feb 2009 to Jan 2010. Patients underwent triple assessment as
      per protocol of the breast screening unit. All had fine needle aspiration and
      core biopsy of the lesions. Appropriate surgery was offered and the size, grade
      and lymph node status were evaluated and Nottingham Prognostic Index (NPI) used
      to predict survival. RESULTS: 5 patients were identified with breast cancers that
      had initial radiological diagnosis of fibroadenoma. All patient lesions were
      screen detected on NHS screening programme. One patient out of five was
      discharged after triple assessment and represented with a lump 18 months later.
      The Median age was 56 years (range 50-66 years). The mammogram showed these to be
      benign-looking lesions and ultrasound scans suggested fibroadenomas as reported
      by specialist breast radiologist. Seven lesions were identified in 5 patients.
      One patient had 3 lesions. Lesions size ranged between 8 mm and 25 mm on
      mammogram (median 14 mm) and 8-20 mm on ultrasound (range 8-20). Fine needle
      aspiration cytology was C5 in the two lesions, C4 in 2 and C3 in 1 lesion. Two
      patients had unifocal grade 3 tumours. One patient had multifocal cancer (3
      cancers - in unilateral breast) all were grade 3 cancers with lymph node
      involvement. One patient had grade 2 cancer and 1 was found to have adenoid
      cystic adenocarcinoma and therefore the grade and NPI were not assessed. NPI was
      good in 1, moderate in 2 and poor in 1 patient. CONCLUSION: Our case series
      suggested that one should have a high index of suspicion for FAD in the
      postmenopausal ladies and triple assessment should include thorough tissue
      sampling in the form of FNA and core biopsy.

PMID- 20804868
TI  - Gel structure has an impact on pericellular and extracellular matrix deposition,
      which subsequently alters metabolic activities in chondrocyte-laden PEG
      hydrogels.
AB  - While designing poly(ethylene glycol) hydrogels with high moduli suitable for in
      situ placement is attractive for cartilage regeneration, the impact of a tighter
      crosslinked structure on the organization and deposition of the matrix is not
      fully understood. The objectives of this study were to characterize the
      composition and spatial organization of new matrix as a function of gel
      crosslinking and study its impact on chondrocytes in terms of anabolic and
      catabolic gene expression and catabolic activity. Bovine articular chondrocytes
      were encapsulated in hydrogels with three crosslinking densities (compressive
      moduli 60, 320 and 590 kPa) and cultured for 25 days. Glycosaminoglycan
      production increased with culture time and was greatest in the gels with lowest
      crosslinking. Collagens II and VI, aggrecan, link protein and decorin were
      localized to pericellular regions in all gels, but their presence decreased with
      increasing gel crosslinking. Collagen II and aggrecan expression were initially
      up-regulated in gels with higher crosslinking, but increased similarly up to day
      15. Matrix metalloproteinase (MMP)-1 and MMP-13 expression were elevated (~25
      fold) in gels with higher crosslinking throughout the study, while MMP-3 was
      unaffected by gel crosslinking. The presence of aggrecan and collagen degradation
      products confirmed MMP activity. These findings indicate that chondrocytes
      synthesized the major cartilage components within PEG hydrogels, however, gel
      structure had a significant impact on the composition and spatial organization of
      the new tissue and on how chondrocytes responded to their environment,
      particularly with respect to their catabolic expression.

PMID- 20804870
TI  - Scar endometriosis - a series of six patients.
AB  - INTRODUCTION: Scar endometriosis is a rare form of extrapelvic endometriosis that
      is usually confused with other surgical or dermatological conditions leading to
      delay in diagnosis. METHODS: We reviewed the case records of patients with the
      diagnosis of scar endometriosis seen in our hospital from January 1996 to
      December 2008. RESULTS: We found six patients of scar endometriosis in 13 years
      making it one of the rare conditions. The median age of the patients was 32.5
      years (range 28-37 years) and median interval from symptoms to treatment was 2
      years (range 1-6 years). Four patients had first presented to either the surgery
      or dermatology physicians. Cyclic pain and swelling at local site was the most
      common presenting symptoms. All patients underwent wide excision of the mass with
      no recurrence of symptoms at a follow up ranging from 9 months to 12 years.
      CONCLUSIONS: Increasing awareness of this condition among doctors can help in
      early diagnosis and treatment with gratifying results.

PMID- 20804871
TI  - Routine postoperative administration of vitamin D and calcium after total
      thyroidectomy: a meta-analysis.
AB  - BACKGROUND: Temporary hypocalcemia is a frequent complication after total
      thyroidectomy. Routine postoperative administration of vitamin D and calcium can
      reduce the incidence of symptomatic postoperative hypocalcemia. We undertook a
      systematic review to assess the effectiveness of this intervention. METHODS: We
      identified randomized controlled trials comparing the administration of vitamin D
      or metabolites to oral calcium or no treatment in patients after total
      thyroidectomy in MEDLINE, EMBASE and LILACS databases. RESULTS: Four studies with
      706 patients were included: 346 in the calcitriol group, 288 in the oral calcium
      group and 72 in the control group. The rates of hypocalcemia symptoms were 4%,
      19% and 31%, respectively. The OR value for the comparison between calcitriol +
      calcium as compared to no treatment and to exclusive calcium treatment groups was
      0.32 (95% CI, 0.13-0.79) and 0.31 (95% CI, 0.14-0.70), respectively. CONCLUSION:
      The prophylactic treatment with vitamin D or metabolites + calcium is effective
      to decrease the incidence of symptoms of temporary hypocalcemia.

PMID- 20804872
TI  - A 5-year analysis of readmissions following elective laparoscopic cholecystectomy
      - cohort study.
AB  - AIMS: This study aimed to determine readmission rates, causes for readmission and
      outcomes for patients undergoing elective Laparoscopic Cholecystectomy (LC)
      without intraoperative cholangiogram (IOC). METHODS: Timing related to
      readmissions was grouped as <6 weeks, 6 weeks-1 year, 1-2 years and >2 years.
      Outcomes and variables related to readmission were evaluated. RESULTS: 101
      readmissions (6.6) were noted amongst 1523 consecutive LC. The median follow up
      was 4 years (range 1.6-6.4 years). There was no difference in the median age (48
      vs. 53 years, P = 0.2) and sex of the patients between the readmitted and no
      readmission groups. The incidence of readmissions (n = 101) within the first 6
      weeks, 6 weeks-1 year, 1-2 years and >2 years were 2.8%, 1.5%, 1.4% and 0.7%
      respectively. The most common reasons for readmissions were non-specific
      abdominal pain (NSAP) (36%), obstructive jaundice (14%), peptic ulcer disease
      (10%), intra-abdominal collection (4%) and bile leak (3%), pancreatitis (3%), and
      other reasons (30%). Overall, 24 (22%) of readmissions were related to biliary
      problems, the majority of these occurred (15/24, 63%) within 6 weeks of LC. The
      incidence of retained stones within the first 6 weeks, 6 weeks-1 year, 1-2 years
      and >2 years were 0.4%, 0.3%, 0.1% and 0% respectively. Overall 14 (14%) patients
      were readmitted with retained stones and all were managed by ERCP & ductal
      clearance. CONCLUSIONS: Readmission rate following elective LC is low with the
      majority occurring within the first 6 weeks and only a quarter of these related
      are directly to biliary pathology. In the absence of routine IOC, around 1% of
      patients present with retained stones within 2 years of LC. A small fraction of
      patients continue to suffer from NSAP and should be warned prior to the surgery.

PMID- 20804873
TI  - Experience with the Wise mammaplasty skin resection pattern in skin-sparing
      mastectomy and immediate breast reconstruction for large breast volumes.
AB  - INTRODUCTION: Skin-sparing mastectomy (SSM) and immediate breast reconstruction
      (IBR) remain technically challenging in very large breasted women, often
      requiring extensive skin reduction, with a high incidence of post-operative
      complications. We report our retrospective experience (1999-2007) with SSM and
      Wise pattern skin reduction in IBR, and examine factors contributing to recipient
      site post-operative complications. RESULTS: 29 reconstructions comprising 16 free
      TRAM/DIEPs, 5 pedicled TRAMs, and 8 implant-based ones were undertaken in 25
      patients aged 32-70 years (median = 48). Their mean BMI was 30.4 kg/m2 (r = 22.3
      39.3) and 6/25 were current smokers. There were 14 (48%) associated axillary
      clearances. All breasts had grade 2 or 3 ptosis. The mastectomies weighed 805 g
      1972 g (mean = 1326). Sixteen operations (55%) developed complications; 7 minor,
      9 requiring further surgical intervention. Of these 16 cases, 13 involved skin
      complications and 9 involved culture-proven wound infections. All patients
      achieved satisfactory aesthetic outcomes. At median cancer follow-up of 24 months
      (r = 2-98), there have been no local recurrences but two deaths from distant
      metastases. Mastectomy weight was significantly associated with major skin
      complications requiring surgery (age-adjusted OR per 100 g = 1.6; CI = 1.1-2.3, p
      = 0.02). Performance of axillary clearance at the time of skin-sparing mastectomy
      was significantly associated with risk of post-operative infection (age-adjusted
      OR = 5.8; CI = 1.3-26.0, p = 0.021). These relationships were maintained after
      adjusting for patient, surgical and tumour factors. CONCLUSION: Wise pattern skin
      reduction is a useful technique for managing large, ptotic breasts during SSM and
      IBR. Increasing breast size and the type of cancer surgery are important
      predictors of post-operative complications.

PMID- 20804874
TI  - In vitro protein expression: an emerging alternative to cell-based approaches.
AB  - Protein expression remains a bottleneck in the production of proteins. Owing to
      several advantages, cell-free translation is emerging as an alternative to cell
      based methods for the generation of proteins. Recent advances have led to many
      novel applications of cell-free systems in biotechnology, proteomics and
      fundamental biological research. This special issue of New Biotechnology
      describes recent advances in cell-free protein expression systems and their
      applications.

PMID- 20804875
TI  - Massive translational repression of gene expression during mouse erythroid
      differentiation.
AB  - We took advantage of a mouse erythroid differentiation system to determine the
      relative contribution of transcriptional and translational control during this
      process. Comparison of expression data obtained with total cytoplasmic mRNAs or
      polysome-bound mRNAs (actively translated mRNAs) on Affymetrix high-density
      oligonucleotide microarrays revealed different characteristics of the two
      regulatory mechanisms. Indeed, mRNA expression from a vast majority of genes was
      affected, albeit most changes were relatively small and occurred at a low pace.
      Translational control, however, affected a smaller fraction of genes but was
      effective at earlier time-points. This analysis unravels six clusters of genes
      showing no significant variation in mRNA expression levels whereas they are
      submitted to translational regulation. Their involvement in terminal mouse
      erythropoiesis may prove to be highly relevant. Furthermore, the data from
      specific and functional categories of genes emphasize that translational control,
      not only reinforces the transcriptional effect, but allows the cell to increase
      the complexity in gene expression regulation patterns.

PMID- 20804878
TI  - Palliative care and end of life care. Preface.

PMID- 20804877
TI  - Adiponectin and bone mass density: The InCHIANTI study.
AB  - INTRODUCTION: Adiponectin serum concentration has been reported to be inversely
      correlated with bone mineral density (BMD) in humans. The data on this issue,
      however, are biased by small study sample size and lack of controlling for body
      composition. METHODS: We used data from the third follow-up of the InCHIANTI
      study, which included measurements of BMD using quantitative CT of the tibia and
      of body composition using bioimpedenziometry. Serum adiponectin was measured
      using radioimmunoassay. We excluded participants with diabetes, hyperthyroidism,
      using hormone replacement or corticosteroid therapy. We evaluated the correlation
      of adiponectin with total, trabecular, and cortical BMD using Pearson's
      coefficient, and linear regression models to estimate the association between
      adiponectin and BMD controlling for potential confounders (age, body mass index,
      alcohol intake, fat mass, smoking). RESULTS: Our sample was made up of 320 men
      (mean age: 67 years, SD: 15.8, range: 29-97 years) and 271 postmenopausal women
      (mean age: 76 years, SD: 8.2, range: 42-97 years). In men, serum adiponectin was
      not independently associated with BMD. In women, after correction for potential
      confounders, adiponectin was associated with total (beta=-0.626, P<0.001),
      trabecular (beta=-0.696, P<0.001), and cortical (beta=-1.076, P=0.001) BMD.
      CONCLUSION: Our results show that adiponectin is inversely associated with bone
      mass in women. Further studies are needed to confirm these findings prospectively
      and then to clarify the explanatory mechanisms.

PMID- 20804876
TI  - Small-molecule regulators that mimic transcription factors.
AB  - Transcription factors (TFs) are responsible for decoding and expressing the
      information stored in the genome, which dictates cellular function. Creating
      artificial transcription factors (ATFs) that mimic endogenous TFs is a major goal
      at the interface of biology, chemistry, and molecular medicine. Such molecular
      tools will be essential for deciphering and manipulating transcriptional networks
      that lead to particular cellular states. In this minireview, the framework for
      the design of functional ATFs is presented and current challenges in the
      successful implementation of ATFs are discussed.

PMID- 20804880
TI  - Symptom management in palliative care and end of life care.
AB  - There is a need for generalist- and specialist-level palliative care clinicians
      proficient in symptom management and care coordination. Major factors
      contributing to this need include changed disease processes and trajectories,
      improved medical techniques and diagnostic testing, successful screening for
      chronic conditions, and drugs that often prolong life. The rapid progressive
      illnesses and deaths that plagued the first half of the twentieth century have
      been replaced in the twenty-first century by increased survival rates. Conditions
      that require ongoing medical care beyond a year define the current chronic
      illness population. Long years of survival are often accompanied by a reduced
      quality of life that requires more medical and nursing care and longer home care.
      This article reviews the management of selected symptoms in palliative and end of
      life care.

PMID- 20804881
TI  - "I want to live, until I don't want to live anymore": involving children with
      life-threatening and life-shortening illnesses in decision making about care and
      treatment.
AB  - Pediatric societies in North America and in the United Kingdom and Europe take
      the position that children should be part of the decision-making process. Less
      clear, however, is how that should be accomplished. This article outlines what
      needs to be considered when taking on the challenge of involving children with
      life-threatening and life-limiting illnesses in decision making regarding care
      and treatment and suggests an approach to involving children that recognizes
      their abilities, vulnerabilities, and relationships with others while at the same
      time ensuring an ethical and meaningful role for children.

PMID- 20804882
TI  - Clinical decision making in palliative care and end of life care.
AB  - Clinical decision making involves a consideration of multiple factors; clinical
      options are constructed based on the objective clinical data and evidence-based
      standards. Technologic advances have led not only to life saving interventions,
      but also to the use of these technologies when benefit to the patient was unclear
      or unexamined. The cases of Karen Quinlan, Nancy Cruzan, and Terri Schiavo
      provide a framework for examining the evolution of clinical decision making,
      including when to use or not to use technologies such as ventilators and
      artificial nutrition and hydration, and the role of specific questions in the
      process. Advance directives are a means to convey patient preferences, however,
      in the absence of advance directives, skilled questioning can elicit patient
      preferences. Nurses' roles in clinical decision making are often nebulous but can
      be enhanced by understanding these interrelated processes, as well as by knowing
      the policies and procedures of their institutions.

PMID- 20804883
TI  - Assessing respiratory distress when the patient cannot report dyspnea.
AB  - Ensuring patient comfort begins with a comprehensive assessment for symptom
      distress. The dying patient poses unique challenges for assessment because of the
      high prevalence of declining and impaired cognition that typifies this
      population. The focus of this paper is on the practical clinical question: How
      can we recognize respiratory distress when the patient cannot provide a report
      about dyspnea?

PMID- 20804885
TI  - Barriers to effective palliative care for low-income patients in late stages of
      cancer: report of a study and strategies for defining and conquering the
      barriers.
AB  - The discipline of palliative care is growing rapidly in the United States but, as
      in many other areas of medical care, multiple barriers exist to providing such
      care to low-income patients with end-stage cancer and other diseases. Reports
      vary with regard to definition and scope of these and other barriers. This
      article briefly reports a pilot study of perceived barriers to palliative care
      and related issues in an urban cancer clinic, reviews the current literature, and
      suggest ways to identify and overcome such barriers in low-income patients with
      cancer.

PMID- 20804886
TI  - End-stage liver disease: challenges and practice implications.
AB  - As the seventh leading cause of death among people aged 25 to 64 years, end-stage
      liver disease (ESLD) affects many Americans in the most productive years of their
      lives. Despite the increasing number of individuals who are dying of ESLD, little
      is documented about their end of life challenges as the disease progresses. The
      purpose of this article is to highlight specific challenges for people with ESLD,
      their families, and their implications for health care providers: ascites,
      spontaneous bacterial peritonitis, hepatic encephalopathy, malnutrition, altered
      drug metabolism, renal insufficiency and hyponatremia, hepatocellular carcinoma,
      and pain. The authors also present a case study to illustrate disease progression
      and difficulties facing patients, family members, and providers.

PMID- 20804884
TI  - Sickle cell disease: an opportunity for palliative care across the life span.
AB  - Sickle cell disease is a chronic illness that affects patients physically and
      emotionally and can do so at an early age. An ecological model of palliative care
      that involves improved communication among the health care team, patients, and
      their families can be beneficial. Open and honest communication regarding advance
      care planning, disease management, relief of pain and other symptoms, and
      bereavement and grief are all important for the patient, family, and health care
      team. Given the multiple acute and chronic complications of sickle cell disease,
      an approach to care that is holistic and comprehensive may help to improve a
      patient's biologic function and the perceived health, functional status, and
      quality of life of the patient and family.

PMID- 20804888
TI  - Recruiting for end of life research: lessons learned in family research.
AB  - A main hurdle for end of life research is recruitment of patients. Researchers
      can enroll interested patients and their families for end of life studies by
      gaining the trust of the hospice staff, who can make valuable referrals of
      patients nearing the end of life. Participants in the study should be made as
      comfortable as possible and not be coerced into the interview process. Once the
      patients have confidence in the researchers, they are more than willing to be a
      part of the research process because it can prove to be cathartic to many of the
      patients and their family members.

PMID- 20804887
TI  - Is a good death possible after withdrawal of life-sustaining therapy?
AB  - Life-sustaining therapy (LST) is commonly withdrawn in critical care units.
      Little is known about the families' perceptions of death when a critically ill
      patient dies after LST is withdrawn. The purpose of this study was to understand
      if families perceived that their family members had a good or a bad death when a
      family member had LST withdrawn after an unexpected, life-threatening illness or
      injury. Twenty-two family members participated in a hermeneutic phenomenological
      study. They were interviewed 1 to 2 years after a family member had died after
      withdrawal of LST. Most family members perceived that their loved ones died a
      good death. Although the timing and circumstances of a person's death may be bad
      in many ways, the actual dying and death can be good.

PMID- 20804889
TI  - Personal relationships and communication messages at the end of life.
AB  - The diagnosis of advanced illness often brings with it an element of limited
      time. Being diagnosed with a life-limiting illness and facing death can evoke
      many painful emotions including anxiety, sadness, and uncertainty. However, it
      can also create the potential for profound growth and transformation. The end of
      life is a time-intensive crucible in which patients and family members have
      important things to express to one another. Embedded in this time are 2 elements
      of daily functioning: personal relationships and communication. Having
      conversations about the relationship and communicating love, gratitude, and/or
      forgiveness may have potential benefits for the dying person and those considered
      close and important.

PMID- 20804891
TI  - Living with cancer: perspectives on a five year journey.
AB  - This is a personal story of the lived experience of the authors, both nurses, who
      as partners face ovarian cancer. We describe the initial impact of such a
      diagnosis and its immediate life-changing consequences, treatment decisions and
      sequelae, remission and recurrence, and choices about living with a chronic
      illness and the ever-present specter of death. We recognize that our experience
      is uniquely ours, yet we believe it has meaning for all patients and caregivers,
      as well as the many health professionals who treat, care for, guide and comfort
      those who bear the burden of cancer.

PMID- 20804890
TI  - Helping parents make and survive end of life decisions for their seriously ill
      child.
AB  - American parents of chronically ill children prefer to be involved in decision
      making about their ill child's end of life care. Parents trust the clinicians
      involved with their ill child to make reasoned judgments on behalf of the ill
      child and to consistently look out for the child's best interests. Parents report
      that having access to understandable information about their child's health
      status influences their ability to participate in end of life decisions. This
      information includes the certainty that all reasonable attempts to save the child
      have been done and in the best possible ways.

PMID- 20804892
TI  - [The meaning and value of words].

PMID- 20804893
TI  - [Long-term follow-up of the efficacy of methotrexate alone or in combination with
      low doses of oral corticosteroids in the treatment of alopecia areata totalis or
      universalis].
AB  - BACKGROUND: Treatment of severe and chronic forms of alopecia areata (AA) totalis
      remains difficult. It has been suggested that methotrexate (MTX) is an
      efficacious treatment for AA totalis. The aim of our study was to assess the long
      term safety and efficacy of MTX in patients with chronic severe forms of AA
      totalis. PATIENTS AND METHODS: Thirty-three patients (24 women and nine men) with
      AA totalis or universalis were included. Mean disease duration was 7.7 years and
      these patients had not responded to prior standard treatment. The initial weekly
      dosage of MTX was 15 mg (n=2), 20mg (n=16) or 25mg (n=15). Nineteen patients
      (58%) were treated with MTX and low doses of corticosteroids (prednisone 10
      20mg/d), while 14 patients (42%) received MTX alone. The primary end-point was
      complete hair regrowth under treatment. RESULTS: Twenty-one patients had total
      hair regrowth and 13 patients were considered as treatment failures, with 10 of
      these having partial regrowth and three having no regrowth. Complete regrowth was
      seen in 12 of 19 patients (63%) on combined treatment and in eight of 14 patients
      (57%) on MTX alone. The onset of hair regrowth was noted after a median delay of
      3 months. At the end of the study, after a median of 30 months' follow-up, the
      median cumulative dose of MTX was 1.8 g (400mg-5.5 g). Relapse was observed on
      corticosteroid dose reduction or withdrawal in 16 of the 20 patients in whom
      total hair regrowth initially occurred. Regrowth after treatment of relapse was
      seen in 14 of these 16 patients (87%). Seven patients experienced adverse events
      consisting of transient elevated transaminases (n=4), persistent nausea (n=2) and
      lymphocytopenia (n=1). CONCLUSION: MTX alone or in combination with low doses of
      oral corticosteroids resulted in complete hair regrowth in about half of these
      patients presenting AA totalis or universalis. Lasting improvement required
      continuous treatment in most cases.

PMID- 20804894
TI  - [Treatment of alopecia areata with prednisone in a once-monthly oral pulse].
AB  - BACKGROUND: Various modalities have been used in the treatment of alopecia areata
      (AA), including pulsed oral corticosteroids. The aim of this study was to
      evaluate the efficacy and safety of pulsed oral prednisone in the management of
      AA. METHODS: This was a prospective study in patients with progressive AA
      affecting more than 40% of the scalp. All patients received 5mg/kg (300 mg) oral
      prednisone once a month for 3 to 6 months and were examined for adverse effects.
      Hair growth was classified as complete, cosmetically acceptable, incomplete or no
      growth. RESULTS: Thirty-four patients (18 men) with a mean age of 12+/-3 years
      were included. AA was ongoing for a mean 2 (1-17) years. Thirteen (38%) patients
      presented multifocal AA, six universalis (20%), six multifocal with ophiasic
      pattern (18%), six totalis (18%), and three ophiasic (6%). Six patients (18%) had
      no regrowth. At 3 months, incomplete or cosmetically acceptable response was
      noted in 28 patients (82%). At 6 months, 14 patients (41%) presented complete
      response, eight patients (23%) had a persistent incomplete response, and six
      patients (18%) had a persistent cosmetically acceptable response. Adverse effects
      were noted in five patients (15%). Variables predictive for no-growth response
      were nail involvement (P=0.001), associated dysimmunity (P=0.017), and
      universalis form (P=0.050). CONCLUSION: A once-monthly oral pulse of 300 mg
      prednisone appears effective and safe. It can be recommended as first-line
      treatment for widespread AA.

PMID- 20804895
TI  - [Activity report on a rapid post-emergency consultation for the management of
      dermatological emergencies [corrected]].
AB  - BACKGROUND: Dermatological emergencies generally consist of infection and
      inflammation, including cutaneous drug reactions. Most patients are either not
      seen again or else are followed by their GP, but it may be a long time before
      they see a dermatologist once more, even if monitoring is necessary. We created a
      rapid post-emergency consultation reserved for these patients alone requiring
      short-term reevaluation, and we report the results of the new consultation
      herein. RESULTS: One consultation per week is exclusively for patients seen in
      dermatological emergency units requiring rapid reassessment (i.e. within two
      weeks) for follow-up or in cases of uncertainty in the diagnosis. Between June
      2008 and June 2009, 40 consultations were carried out, with 370 patients being
      enrolled and 214 attending the consultation (40% absenteeism), i.e. 3% of
      emergency unit patients. The mean time from the emergency consultation was 9.2
      days and the reasons for consultation were: 34% infectious dermatoses, 36%
      inflammatory dermatoses, 7.5% cutaneous drug reactions and 19% miscellaneous
      diagnosis, with 4.2% uncertainty about diagnosis. The outcome after the emergency
      consultation was favourable in 76% of cases (complete healing or improvement). A
      follow-up consultation was proposed in 41.5% of cases, with 77.5% of patients
      attending. While the creation of this consultation did not significantly reduce
      the number of patients returning to the emergency service, it was welcomed by all
      dermatologists in charge of such dermatological emergency services. CONCLUSION:
      This rapid post-emergency consultation forms a small part of the activities of
      the dermatological emergency unit but is positive in the view of the
      dermatologists in charge of emergency consultations since it means patients can
      be given appointments soon after initial treatment, thus avoiding the need to
      return to the emergency unit. The diseases seen at this unit are similar to those
      seen in the emergency unit. While absenteeism is considerable, this type of
      consultation results in the organisation of further ongoing care for 40% of
      patients, most of whom comply with treatment.

PMID- 20804896
TI  - [Management of cutaneous B-cell lymphoma: recommendations of the French cutaneous
      lymphoma study group].
AB  - AIMS: To provide recommendations for the treatment of cutaneous B-cell lymphomas
      (CBCL). METHODS: Literature review and expert opinions from the French Cutaneous
      Lymphoma Study Group. RESULTS: Diagnosis of marginal zone BCL (MZ BCL),
      centrofollicular BCL (CF BCL) or cutaneous large B-cell lymphoma, leg type
      (CLBCL, LT) is based on combination of clinical signs and histopathological
      features, together with B-cell clonality analyses whenever possible. Staging
      relies on straightforward laboratory examinations and imaging, completed in
      selected cases with bone marrow biopsy. Treatment may be topical, including
      excision, curative radiotherapy (30Gray) or adjunctive/low dose (4Gray)
      radiotherapy, topical corticosteroids, interferon or intralesional rituximab; or
      systemic, using chemotherapy and/or intravenous rituximab. For indolent forms of
      the disease (MZ CBCL and CF CBCL), curative (30Gray) may be given as first-line
      treatment in patients with localized lesions or few scattered skin lesions. For
      more numerous slow-growing lesions with a low tumour burden, simple monitoring
      with adjunctive ad hoc local treatment of individual lesions is acceptable. For
      multiple growing lesions, systemic rituximab or chlorambucil may be proposed.
      Polychemotherapy should only be used for progressive forms unresponsive to
      previous therapies. CLBCL LT forms are more aggressive and occur in older
      subjects. These lymphomas are best treated with age-adapted combinations of
      polychemotherapies and rituximab. CONCLUSION: Appropriate clinical trials are
      still needed to strengthen the levels of evidence of current recommendations.

PMID- 20804897
TI  - [Annular elastolytic giant-cell granuloma].
AB  - BACKGROUND: Annular elastolytic giant-cell granuloma (AEGCG) is a rare form of
      granulomatous dermatosis characterized by annular plaques with central atrophy
      and raised erythematous margins and is usually located on the facial and neck
      areas. It is characterized histologically by loss of elastic fibre and
      elastophagocytosis. We report a case of AEGCG. CASE REPORT: A 72-year-old man
      consulted for annular plaques, some of which were atrophic, and papules that had
      been present for 2 years. The lesions involved sun-exposed and non-sun-exposed
      skin. The biopsies showed granulomatous infiltrates and discrete
      elastophagocytosis. After ruling out various differential clinical and
      histological diagnoses, the patient was diagnosed with AEGCG. DISCUSSION: We
      report a case of AEGCG. Diagnosis was not easy. The differential diagnoses of
      this entity were discussed and we ruled out actinic granuloma, sarcoidosis,
      leprosy, and granuloma annulare. Our patient presented the classical annular
      variant combined with a papular variant. We report the first case involving
      response to isotretinoin.

PMID- 20804898
TI  - [Annular elastolytic giant cell granuloma].
AB  - BACKGROUND: Annular elastolytic giant cell granuloma (AEGCG) is a rare form of
      granulomatous dermatosis. It is characterised histologically by phagocytosis of
      elastic fibres by multinucleated cells. We report a favourable outcome in a case
      of AEGCG following PUVA therapy and treatment with synthetic antimalarials.
      PATIENTS AND METHODS: A 67-year-old retired wine grower presented with highly
      pruritic annular lesions with raised borders on the shoulders and trunk that had
      been present for several months. Histological examination of a biopsy sample from
      the erythematous border was characteristic of AEGCG. Various topical treatments
      proved ineffective and systemic corticosteroids attenuated the patient's pruritus
      but had no effect on the skin lesions. PUVA therapy resulted in regression of
      lesions on the trunk, but the rash spread to the patient's arms and was covered
      with epidermal microcysts. PUVA therapy was discontinued and treatment with a
      synthetic antimalarial (hydroxychloroquine 400mg/d) was initiated, resulting in
      complete regression of the lesions. DISCUSSION: AEGC was isolated in 1979 by
      Hanke et al. on the basis of five cases seen in females. This is a rare form of
      dermatosis with some 30 cases being reported in the English literature. The
      clinical aspect is fairly evocative, with erythematous papular lesions, either
      alone or in groups, with a raised border and a lighter centre tending towards
      atrophy. In most cases, the lesions are found predominantly in areas exposed to
      sunlight. The histological appearance is characteristic, with an image of giant
      cell elastophagic granuloma from which the name of the disease is taken. This
      appearance allows the disease to be differentiated from a number of other
      granulomatous diseases. The aetiology is unknown and treatment is empirical.
      Spontaneous cure can occur and consistent results have not been obtained with any
      treatments. In our case, PUVA was partly successful, and the synthetic
      antimalarials resulted in complete regression of residual lesions.

PMID- 20804899
TI  - [Hypocomplementemic vasculitis treated with dapsone].
AB  - BACKGROUND: Hypocomplementemic urticarial vasculitis, described by MacDuffie in
      1973, is rare. Some doubt surrounds its classification. We report a case of
      hypocomplementemic urticarial vasculitis (MacDuffie syndrome) treated with
      dapsone with a favorable outcome. CASE REPORT: Over a number of years, a 43-year
      old man presented urticarial vasculitis attacks with palpebral oedema and
      systemic symptoms such as fever and arthralgia. In 2006, MacDuffie syndrome was
      diagnosed on the grounds of positive anti-C1q antibodies. Treatment with dapsone
      was started and resulted in considerable improvement. DISCUSSION:
      Hypocomplementemic urticarial vasculitis is characterized by urticarial
      vasculitis lesions, leucocytoclastic vasculitis and systemic symptoms. The latter
      symptoms are similar to those of systemic lupus erythematosus (SLE), and some
      authors have suggested that MacDuffie syndrome may in fact belong to SLE.
      Diagnosis is based on clinical appearance, histology and the presence of anti-C1q
      antibodies. There is no specific treatment for hypocomplementemic urticarial
      vasculitis. Immunosuppressant therapy can be used for lesions refractory to
      systemic corticosteroids.

PMID- 20804900
TI  - [Efficacy of infliximab in the treatment of follicular occlusion triad].
AB  - BACKGROUND: Dermatological treatments for the follicular occlusion triad have
      only partial and transient efficacy. PATIENTS AND METHODS: A 20-year-old patient
      presented folliculitis of the scalp, acne and hidradenitis suppurativa,
      associated with spondyloarthritis. Treatment with infliximab for rheumatologic
      symptoms induced complete and lasting dermatological and rheumatological
      remission. COMMENTS: The efficacy of anti-TNF-alpha in follicular occlusion triad
      provided confirmation that infection is not at the heart of the aetiological
      process. However, efficacy data is still sparse and additional studies are
      required.

PMID- 20804901
TI  - [Intracranial extension of cutaneous facial squamous cell carcinoma: involvement
      of the neurotropic pathway].
AB  - BACKGROUND: Squamous cell carcinoma is the most common form of skin cancer after
      basal cell carcinoma. It comprises locoregional malignant tumours with more rapid
      and severe spread, and which may metastasise through blood or lymph, and through
      a less well-known neurotropic pathway. We report a case of late and slowly
      progressive recurrence of squamous cell carcinoma revealed and characterized by
      neurological symptoms alone. OBSERVATION: A 69-year-old woman with a history of
      cutaneous squamous cell carcinoma on the left nostril edge removed 10 years
      earlier presented right trigeminal neuralgia in 2003. These symptoms gradually
      expanded and in 2007 a subcutaneous induration of the two cheeks appeared.
      Magnetic resonance imaging (MRI) showed subcutaneous infiltration of the 2
      nasolabial sulci, as did contrast enhancement of the two trigeminal nerves up to
      the cavernous sinuses. Deep biopsy allowed a diagnosis of invasive squamous cell
      carcinoma to be made. DISCUSSION: Neurotropism is an important feature of
      squamous cell carcinoma, and reveals the aggressive nature of this condition.
      This feature makes it hard to diagnose relapse since the neurological symptoms
      may be isolated for a long period, hence the need for systematic screening for
      perineural tumour sites on histological analysis of the initial lesion. Treatment
      for these forms is limited and for the moment consists of radiation, cetuximab
      and a combination of these two treatments.

PMID- 20804902
TI  - [Unusual axillary apocrine carcinoma of the skin: histological diagnostic
      difficulties].
AB  - BACKGROUND: Apocrine carcinoma of the skin (ACS) is a rare adnexal neoplasm
      presenting as an indurated slow-growing dermal or subcutaneous plaque that often
      occurs in the axilla. Histological distinction between ACS and cutaneous
      metastases of breast carcinoma may be difficult. OBSERVATION: A 64-year-old man
      presented with a slowly growing left axillary mass, which he had noticed for 2
      years, without any other functional or clinical symptoms. Histological
      examination of the skin biopsy showed dermal invasion with atypical cells in an
      "Indian file" pattern. The pattern of the tumour and immunohistochemical staining
      suggested a diagnosis of breast carcinoma metastasis. However, the history of a
      slow-growing tumour and negative initial testing for a primary adenocarcinoma
      supported the hypothesis of ACS. DISCUSSION: A 100 cases of ACS have been
      reported in the literature with the main site being the axillary area. The
      differential diagnostic between axillary ACS and metastasis of lobular breast
      carcinoma has been discussed recently. Diagnosis may be difficult since the
      pattern of the tumour can be misleading and immunomarkers are not always
      specific. CONCLUSION: We report a new case of axillary ACS histologically
      mimicking lobular breast carcinoma metastasis.

PMID- 20804903
TI  - [Myiasis of the scalp due to Wohlfahrtia magnifica].

PMID- 20804904
TI  - [Ulcerated necrobiosis lipoidica: successful treatment with topical tacrolimus
      and hydroxychloroquine].

PMID- 20804905
TI  - [Mycosis fungoides with depigmentation].

PMID- 20804906
TI  - [Tobacco and skin].

PMID- 20804907
TI  - [Peripheral globules].

PMID- 20804908
TI  - [Hair and genes: continuing progress].

PMID- 20804909
TI  - [Palmoplantar hidradenitis].

PMID- 20804910
TI  - [Cutaneous fistula revealing tubercular pyonephrosis].

PMID- 20804911
TI  - [Tattoo removal at the start of the 20th century].

PMID- 20804912
TI  - [Desloratadine and mouth ulcers].

PMID- 20804913
TI  - Development of a multiplex MethyLight assay for the detection of multigene
      methylation in human colorectal cancer.
AB  - In peripheral blood, cell-free methylated DNA has been reported to be a useful
      biomarker of noninvasive blood screening for the detection of colorectal cancer
      (CRC), including the genes ALX homeobox 4 (ALX4), septin 9 (SEPT9), or
      transmembrane protein with EGF-like, and two follistatin-like domains 2 (TMEFF2).
      Here we report a multiplex MethyLight polymerase chain reaction (PCR) assay that
      simultaneously detected the methylation status of ALX4, SEPT9, and TMEFF2, as
      well as quantifying methylation level of these genes in a total of 127 fresh
      tissue samples and 182 peripheral blood samples from CRC patients. Using the
      multiplex MethyLight assay, methylated ALX4, SEPT9, and TMEFF2 occurred in 56,
      78, and 75% of CRC tissue samples and in 48, 75, and 71% of peripheral blood
      samples from CRC patients. The sensitivities of the combined study using the
      three genes as biomarkers for the detection of CRC in primary tissues and
      peripheral blood samples were 84 and 81%, with specificities of 87 and 90%,
      respectively. Combining the specificity of real-time PCR, the high throughput of
      multiplex PCR, and the high sensitivity of multigene detection, this multiplex
      MethyLight PCR assay may allow for future screening programs with large-scale
      noninvasive blood testing for early-stage CRC.

PMID- 20804915
TI  - Deep fibrous histiocytoma with a clonal karyotypic alteration: molecular
      cytogenetic characterization of a t(16;17)(p13.3;q21.3).
AB  - Deep fibrous histiocytoma, a rare lesion occuring in deep soft tissues, has
      recently been formally characterized as a diagnostically distinguishable variant
      of the benign fibrous histiocytoma spectrum with distinct morphological features.
      Nevertheless, because of the small number of cases published, information on
      their clinical behavior, including propensity for local recurrence and
      metastasis, is quite limited, and no molecular genetic or cytogenetic data are
      available. We report a 46,XY,t(16;17)(p13.3;q21.3) karyotype in a deep fibrous
      histiocytoma. Fluorescence in situ hybridization using bacterial artificial
      chromosome (BAC) clones refined the translocation breakpoints within 119.9 kb at
      16p13.3 and 214 kb at 17q21.3. Moreover, to ascertain whether they may be
      nonrandomly involved in changes in this rare tumor type, we designed two dual
      color break-apart probes with BAC clones, mapping proximally and distally to the
      two breakpoints, to be tested in additional archival cases by interphase
      fluorescence in situ hybridization. No break-apart signals were observed in the
      six additional cases studied, indicating either that the translocation is
      sporadic or that it is rare in deep fibrous histiocytoma. In conclusion, our data
      show that chromosome aberrations may be found in deep fibrous histiocytoma and
      that, as with cutaneous lesions, they may have clonal, at present nonrecurrent,
      chromosome changes.

PMID- 20804914
TI  - Fusion of HMGA2 to COG5 in uterine leiomyoma.
AB  - Uterine leiomyomas are smooth muscle tumors most commonly seen in middle-aged
      women. Approximately 10% of these tumors contain rearrangements of the chromatin
      remodeling gene HMGA2 at the chromosome band 12q14.3. Herein, we report on a
      uterine leiomyoma with a novel HMGA2 fusion gene. A 44-year-old woman presented
      with a 20-cm mass uterine leiomyoma. From a histological standpoint, the tumor
      exhibited extensive hyalinization, very low mitotic activity (<1/10 HPH), and no
      cytologic atypia. Smooth muscle differentiation was confirmed by the expression
      of smooth muscle actin and desmin. Standard cytogenetic analysis showed the
      reciprocal translocation t(7;12)(q31.2;q14.3). Fluorescence in situ hybridization
      analysis confirmed a balanced rearrangement of the HMGA2 locus in 80% of the
      cells. 3'RACE reverse-transcription polymerase chain reaction identified the
      fusion of HMGA2 exon 4 to the COG5 locus on 7q31 (component of oligomeric golgi
      complex 5 isoform). The fusion sequence is predicted to encode a 96-amino acid
      chimeric protein that retains all three DNA-binding domains (AT hooks) of HMGA2,
      but that is shorter than the original HMGA2 protein. Since the general structure
      of the fusion gene is similar to other previously described HMGA2 fusions, its
      biologic activity is predicted to be likely similar.

PMID- 20804916
TI  - ETV6-ARNT fusion in a patient with childhood T lymphoblastic leukemia.
AB  - The ETS variant gene 6 (ETV6) gene is located at 12p13, and is frequently
      involved in translocations in various human neoplasms, resulting in the
      expression of fusion proteins consisting of the amino-terminal part of ETV6 and
      unrelated transcription factors or protein tyrosine kinases. Leukemia with
      t(1;12)(q21;p13) was previously described in a 5-year-old boy with acute
      myeloblastic leukemia (AML-M2) who exhibited a novel ETV6-aryl hydrocarbon
      receptor nuclear translocator (ARNT) fusion protein. We herein report the case of
      a 2-year-old boy with T-cell lymphoblastic leukemia (T-ALL) harboring
      t(1;12)(q21;p13). Fluorescence in situ hybridization (FISH) with a ETV6 dual
      color DNA probe revealed that the split signals of the ETV6 gene in 96.7% of bone
      marrow cells, indicating rearrangement of the ETV6 gene. Therefore, we performed
      a FISH analysis with bacterial artificial chromosome (BAC) probes containing the
      ARNT, BCL9, and MLLT11 genes located at 1q21, and these results indicated that
      the ARNT gene might be involved in the t(1;12)(q21;p13). Reverse transcriptase
      polymerase chain reaction analysis disclosed the existence of a ETV6-ARNT fusion
      gene. To our knowledge, the current report is novel in its report of the ETV6
      ARNT fusion in childhood T-ALL. The ETV6-ARNT fusion is associated not only with
      AML but also with T-ALL.

PMID- 20804917
TI  - Novel BRCA1/2 mutations in Serbian breast and breast-ovarian cancer patients with
      hereditary predisposition.
AB  - Mutations in breast cancer susceptibility (BRCA) genes lead to defects in DNA
      repair processes resulting in elevated genome instability and predisposing to
      breast and ovarian cancer. The study was designed to detect mutational spectra of
      BRCA1/2 genes in a Serbian population. Using automated DNA sequencing, we tested
      individuals for BRCA mutations, based on positive family history of either breast
      or ovarian cancer or both. Two novel mutations (c.4765_4784del in BRCA1 exon 15
      and c.4367_4368dupTT in BRCA2 exon 11) were detected, in three probands from two
      different families. These mutations have not been reported previously in the BIC
      or LOVD databases. Protein products of these mutated alleles lack domains
      necessary for their DNA repair functions, an indicator that these are deleterious
      mutations. Neither mutation was found in any proband from 50 other families with
      hereditary predisposition, so the two mutations are likely family-specific rather
      than population-specific. Although BRCA1-associated tumors are typically negative
      for estrogen receptor (ER), progesterone receptor (PR), and ERBB2, the novel
      BRCA1 mutation identified in this study was detected in a proband with ER- and PR
      positive breast cancer. Steroid receptor-positive BRCA-related breast cancer in
      this proband supports the idea of characteristic pathological features and older
      age of onset among BRCA1-mutated ER-positive breast cancers.

PMID- 20804918
TI  - Amplification of the RARA gene in acute myeloid leukemia: significant finding or
      coincidental observation?
AB  - Oncogene amplification resulting in aberrant expression, although common in solid
      tumors, is rare in acute myeloid leukemia (AML) and is mostly associated with
      amplification of MYC, RUNX1, and MLL genes. Retinoic acid receptor alpha (RARA)
      and other target sequences at 17p11.2 often represent the amplicons expressed in
      breast cancer, not in AML. We present a unique case of a 59-year-old female with
      a history of breast cancer, now presenting with pancytopenia and bilateral
      infiltration with effusion in nodules of the right upper lobe of the lung. She
      was diagnosed with AML-M5. Chromosome analysis demonstrated a hypodiploid clone
      with complex numerical/structural abnormalities including 5q deletion, monosomy
      7, as well as structurally rearranged chromosome 11 and several marker
      chromosomes. Fluorescence in situ hybridization (FISH) analysis showed
      amplification of RARA, loss of 7q, monosomy 7, loss of DEK (6p23), and additional
      copies of NUP214 (9q34) and MLL (11q23). Additional FISH studies showed both
      ERBB2 and TOP2A genes, which were co-amplified on one of the marker chromosomes.
      The follow-up bone marrow did not yield any metaphases, but FISH was normal for
      all probes, including RARA. After a short remission, the patient relapsed and
      showed clonal evolution. Additional case reports are necessary to assess whether
      RARA amplification in hematologic malignancies serves as an independent
      prognostic factor.

PMID- 20804919
TI  - A case of angioimmunoblastic T-cell non-Hodgkin lymphoma with a neocentric inv
      dup(1).
AB  - Neocentromeres are rare epigenetic phenomena in which functional centromeres are
      formed onto novel chromosomal locations without any alpha-satellite DNA. To date,
      constitutional human neocentromeres have been reported in at least 90 cases. In
      cancer, however, the knowledge is much more limited. Acquired neocentromeres have
      been described in a particular class of lipomatous tumors (atypical lipomas and
      well-differentiated liposarcomas; ALP-WDLPS), three cases of acute myeloid
      leukemia (AML), one case of non-Hodgkin lymphoma (NHL), and one case of lung
      carcinoma. Here, we report on a 66-year-old male with angioimmunoblastic T-cell
      NHL. Cytogenetic analysis of his bone marrow showed multiple aberrations,
      including the presence of a supernumerary chromosome. Using the fluorescence in
      situ hybridization technique, the supernumerary chromosome was demonstrated to be
      entirely composed of material derived from chromosome 1. It represented an
      inverted duplication of the segments between 1q21 and 1qter with a neocentromere
      in band 1q31. To our knowledge, this is the second reported case of NHL (both T
      cell) with the presence of a neocentromere. The occurrence of neocentromeres in
      tumor cells, however, may be underestimated because of technical limitations
      during the routine diagnostic chromosomal analysis. The prognostic impact is
      therefore currently unknown.

PMID- 20804920
TI  - Acute myeloid leukemia associated with t(10;17)(p13-15;q12-21) and phagocytic
      activity by leukemic blasts: a clinical study and review of the literature.
AB  - Translocation (10;17)(p13-15;q12-21) in acute leukemia is rarely reported in the
      literature. Here, we present both a novel t(10;17) case study and a review of
      relevant literature on t(10;17) in acute leukemia (10 cases). In summary, we came
      to the following preliminary conclusions: t(10;17) is associated with poorly
      differentiated acute leukemia subtype [90%; eight cases of acute myeloid leukemia
      (AML M0, M1) and one case of acute undifferentiated leukemia], phagocytic
      activity by blasts occurs (30%), and the survival time was short in three of the
      seven t(10;17) cases for whom follow-up data were available (median, 8 months).
      More clinical studies concerning the prognosis, treatment response, and survival
      of patients with t(10;17) are necessary.

PMID- 20804921
TI  - Characterization of FRA7B, a human common fragile site mapped at the 7p
      chromosome terminal region.
AB  - Common fragile sites (CFS) are specific regions of the mammalian chromosomes that
      are particularly prone to gaps and breaks. They are a cause of genome
      instability, and the location of many CFS correlates with breakpoints of
      aberrations recurrent in some cancers. The molecular characterization of some CFS
      has not clarified the causes of their fragility. In this work, by using
      fluorescence in situ hybridization analysis with BAC and PAC clones, we
      determined the DNA sequence of the CFS FRA7B. The FRA7B sequence was then
      analyzed to identify coding sequences and some structural features possibly
      involved in fragility. FRA7B spans about 12.2 megabases, and is therefore one of
      the largest CFS analyzed. It maps at the 7p21.3-22.3 chromosome bands, therefore
      at the interface of G- and R-band regions that are probably difficult to
      replicate. A 90-kilobase long sequence that presents very high flexibility values
      was identified at the very beginning of the more fragile CFS region. Three large
      genes (THSD7A, SDK1, and MAD1L1) and two miRNA genes (MIRN589 and MIRN339) map in
      the fragile region. The chromosome band 7p22 is a recurrent breakpoint in
      chromosome abnormalities in different types of neoplasm. FRA7B is the first
      characterized CFS located in a chromosome terminal region.

PMID- 20804922
TI  - Cell culture and senescence in uterine fibroids.
AB  - The in vitro growth of cells from uterine fibroids is characterized by an early
      onset of senescence. Often, an even lower growth potential than that of matching
      myometrial cells is noted. Also, the tremendous differences in the expression of
      the high mobility group protein HMGA2 seen when comparing fibroids of different
      genetic subtypes are surprisingly not reflected by significant differences in
      their growth potential in vitro. We aimed to evaluate possible changes of the
      HMGA2 expression level between the native tissue and cell cultures, so we
      performed quantitative real-time polymerase chain reaction studies that revealed
      a marked decrease of the HMGA2 mRNA in culture in those cases with overexpression
      of HMGA2. In the two cases initially showing the highest expression, it decreased
      by approximately 97%. Associated with the decrease of HMGA2 was a clearly
      increased expression of the senescence-associated p19(Arf). Together, these
      findings explain the similar behavior of cell cultures from fibroids of different
      genetic subgroups and may also offer an explanation for the early onset of in
      vitro senescence in these cell cultures.

PMID- 20804923
TI  - Array comparative genomic hybridization in the detection of chromosomal
      abnormalities in T-cell prolymphocytic leukemia.

PMID- 20804924
TI  - MYC in gastric carcinoma and intestinal metaplasia of young adults.

PMID- 20804925
TI  - Analysis of the frequency of GNAS codon 201 mutations in advanced colorectal
      cancer.

PMID- 20804926
TI  - Rescuing Sisyphus: the team approach to amputation prevention.

PMID- 20804927
TI  - History of the team approach to amputation prevention: pioneers and milestones.
AB  - BACKGROUND: This historical perspective highlights some of the pioneers,
      milestones, teams, and system changes that have had a major impact on the
      management of the diabetic foot during the past 100 years. In 1934, American
      diabetologist Elliott P. Joslin noted that mortality from diabetic coma had
      fallen from 60% to 5% after the introduction of insulin, yet deaths from diabetic
      gangrene of the lower extremity had risen significantly. He believed that
      diabetic gangrene was preventable. His remedy was a team approach that included
      foot care, diet, exercise, prompt treatment of foot infections, and specialized
      surgical care. RESULTS: The history of a team approach to management of the
      diabetic foot chronicles the rise of a new health profession, Podiatric Medicine
      and Surgery, as well as the emergence of the specialty of Vascular Surgery. The
      partnership between the diabetologist, vascular surgeon, and podiatrist is a
      natural one. The complementary skills and knowledge of each can improve limb
      salvage and functional outcomes. Comprehensive multidisciplinary foot care
      programs have been shown to increase quality of care and reduce amputation rates
      by 36% to 86%. The development of distal revascularization techniques to restore
      pulsatile blood flow to the foot has also been a major advancement. CONCLUSION:
      Diabetic foot patients are among the most complex and vulnerable of all patient
      populations. Specialized diabetic foot clinics of the 21st century should be
      multidisciplinary and equipped to coordinate diagnosis, off-loading, and
      preventive care; perform revascularization procedures; aggressively treat
      infections; and manage medical comorbidities.

PMID- 20804928
TI  - The costs of diabetic foot: the economic case for the limb salvage team.
AB  - BACKGROUND: In 2007, the treatment of diabetes and its complications in the
      United States generated at least $116 billion in direct costs; at least 33% of
      these costs were linked to the treatment of foot ulcers. Although the team
      approach to diabetic foot problems is effective in preventing lower extremity
      amputations, the costs associated with implementing a diabetic foot care team are
      not well understood. An analysis of these costs provides the basis for this
      report. RESULTS: Diabetic foot problems impose a major economic burden, and costs
      increase disproportionately to the severity of the condition. Compared with
      diabetic patients without foot ulcers, the cost of care for patients with a foot
      ulcer is 5.4 times higher in the year after the first ulcer episode and 2.8 times
      higher in the second year. Costs for the treatment of the highest-grade ulcers
      are 8 times higher than for treating low-grade ulcers. Patients with diabetic
      foot ulcers require more frequent emergency department visits, are more commonly
      admitted to hospital, and require longer length of stays. Implementation of the
      team approach to manage diabetic foot ulcers within a given region or health care
      system has been reported to reduce long-term amputation rates from 82% to 62%.
      Limb salvage efforts may include aggressive therapy, such as revascularization
      procedures and advanced wound healing modalities. Although these procedures are
      costly, the team approach gradually leads to improved screening and prevention
      programs and earlier interventions, and thus seems to reduce long-term costs.
      CONCLUSIONS: To date, aggressive limb preservation management for patients with
      diabetic foot ulcers has not usually been paired with adequate reimbursement. It
      is essential to direct efforts in patient-caregiver education to allow early
      recognition and management of all diabetic foot problems and to build integrated
      pathways of care that facilitate timely access to limb salvage procedures.
      Increasing evidence suggests that the costs for implementing diabetic foot teams
      can be offset over the long-term by improved access to care and reductions in
      foot complications and in amputation rates.

PMID- 20804929
TI  - Toe and flow: essential components and structure of the amputation prevention
      team.
AB  - At the end of an anatomic peninsula, the foot in diabetes is prone to acute and
      chronic complications involving neuropathy, vasculopathy, and infection.
      Effective management requires an interdisciplinary effort focusing on this triad.
      In this article, we describe the key factors leading to foot complications and
      the critical skill sets required to assemble a team to care for them. Although
      specific attention is given to a conjoined model involving podiatry and vascular
      surgery, the "toe and flow" model, we further outline three separate models of
      care--basic, intermediate, and center of excellence--that can be implemented in
      the developed and developing world.

PMID- 20804930
TI  - What you can't feel can hurt you.
AB  - Throughout our medical training, we are taught how to manage patients who present
      with symptoms, which usually leads to a clinical examination, a diagnosis, and a
      management plan. However, virtually no time is spent on teaching how to manage
      patients who have no symptoms because they have lost the ability to feel pain;
      that is, they have peripheral neuropathy. The lifetime incidence of foot
      ulceration in people with diabetes has been estimated to be as high as 25%, and a
      number of contributory factors result in a foot being at risk of ulceration. Most
      important amongst these factors is peripheral neuropathy, or the loss of the
      ability to feel pain, temperature, or pressure sensation in the feet and lower
      legs. Up to 50% of older patients with type 2 diabetes have evidence of sensory
      loss that puts them at risk of foot ulceration. If we are to succeed in reducing
      the high incidence of foot ulcers, regular screening for peripheral neuropathy is
      vital in all patients with diabetes. Those found to have any risk factors for
      foot ulceration require special education and more frequent review, particularly
      with podiatrists. The key message is therefore that neuropathic symptoms
      correlate poorly with sensory loss, and their absence must never be equated with
      lack of risk of foot ulceration. If we are to succeed in reducing the high
      incidence of foot ulceration and, particularly, recurrent ulceration, we must
      realize that with loss of pain there is also diminished motivation in the healing
      and the prevention of injury.

PMID- 20804931
TI  - Debridement of the noninfected wound.
AB  - The utility of wound debridement has expanded to include the management of all
      chronic wounds, even in the absence of infection and gross necrosis. Biofilm,
      metalloproteases on the wound base, and senescent cells at the wound edge
      irreversibly change the physiology of wound healing and contribute to a
      pathologic, chronic inflammatory environment. The objective of this review is to
      provide surgeons with a baseline understanding of the processes of debridement in
      the noninfected wound.

PMID- 20804932
TI  - Off-loading the diabetic foot for ulcer prevention and healing.
AB  - BACKGROUND: Retrospective and prospective studies have shown that elevated
      plantar pressure is a causative factor in the development of many plantar ulcers
      in diabetic patients and that ulceration is often a precursor of lower extremity
      amputation. In this article, we review the evidence that relieving areas of
      elevated plantar pressure (off-loading) can prevent and heal plantar ulceration.
      RESULTS: There is no consensus in the literature concerning the role of off
      loading through footwear in primary or secondary prevention of ulcers. This is
      likely due to the wide diversity of intervention and control conditions tested,
      the lack of information about off-loading efficacy of the footwear used, and the
      absence of a target pressure threshold for off-loading. Uncomplicated plantar
      ulcers should heal in 6 to 8 weeks with adequate off-loading. The total contact
      cast and other nonremovable devices are most effective because they eliminate the
      problem of nonadherence to recommendations for using a removable device.
      Conventional or standard therapeutic footwear is not effective in ulcer healing.
      Recent United States and European surveys show a large discrepancy between
      guidelines and clinical practice in off-loading diabetic foot ulcers. Many
      clinics continue to use methods that are known to be ineffective or have not been
      proven effective, while ignoring methods that have been demonstrated to be
      efficacious. CONCLUSIONS: A number of strategies are proposed to address this
      situation, notably the adoption and implementation of recently established
      international guidelines, which are evidence-based and specific, by professional
      societies in the United States and Europe. Such an approach would change the
      often poor current expectations for healing diabetic plantar ulcers.

PMID- 20804933
TI  - Surgical off-loading of the diabetic foot.
AB  - Surgical intervention for chronic deformities and ulcerations has become an
      important component in the management of patients with diabetes mellitus. These
      patients are no longer relegated to wearing cumbersome braces or footwear for
      deformities that might otherwise be easily corrected. Although surgical
      intervention in these often high-risk individuals is not without risk, the
      outcomes are fairly predictable when patients are properly selected and
      evaluated. In this brief review, we discuss the rationale and indications for
      diabetic foot surgery, focusing on the surgical decompression of deformities that
      frequently lead to foot ulcers.

PMID- 20804934
TI  - Wound care: the role of advanced wound healing technologies.
AB  - Wound repair and regeneration is a highly complex combination of matrix
      destruction and reorganization. While major hurdles remain, advances over the
      past generation have improved the clinician's armamentarium in the medical and
      surgical management of this problem. The purpose of this manuscript is to review
      the current literature regarding the pragmatic use of three of the most commonly
      employed advanced therapies; namely, bioengineered tissue, negative pressure
      wound therapy, and hyperbaric oxygen therapy with a focus on the near-term future
      of wound healing, including stem cell therapy.

PMID- 20804935
TI  - Medical therapy of diabetic foot infections.
AB  - Diabetic foot infections are a common and often serious problem, accounting for a
      greater number of hospital bed days than any other complication of diabetes.
      Despite advances in both antibiotic therapy and surgical management, these
      infections continue to be a major risk factor for amputations of the lower
      extremity. Although a number of wound size and depth classification systems have
      been adapted for use in codifying diabetic foot ulcerations, none are specific
      for infection. In 2003, the International Working Group on the Diabetic Foot
      developed guidelines for managing diabetic foot infections, including the first
      severity scale specific for these infections. The following year, the Infectious
      Diseases Society of America (IDSA) published their Diabetic Foot Infection
      Guidelines. In this article, we review some of the critical points from the
      Executive Summary of the IDSA document and provide a commentary following each
      issue to update the reader on any pertinent changes that have occurred since the
      publication of the original document in 2004. The importance of a
      multidisciplinary limb salvage team, apropos this special joint issue of the
      American Podiatric Medical Association and the Society for Vascular Surgery,
      cannot be overstated.

PMID- 20804936
TI  - A step-wise approach for surgical management of diabetic foot infections.
AB  - Diabetic foot disease frequently leads to substantial long-term complications,
      imposing a huge socioeconomic burden on available resources and health care
      systems. Peripheral neuropathy, repetitive trauma, and peripheral vascular
      disease are common underlying pathways that lead to skin breakdown, often setting
      the stage for limb-threatening infection. Individuals with diabetes presenting
      with foot infection warrant optimal surgical management to effect limb salvage
      and prevent amputation; aggressive short-term and meticulous long-term care plans
      are required. In addition, the initial surgical intervention or series of
      interventions must be coupled with appropriate systemic metabolic management as
      part of an integrated, multidisciplinary team. Such teams typically include
      multiple medical, surgical, and nursing specialties across a variety of public
      and private health care systems. This article presents a stepwise approach to the
      diagnosis and treatment of diabetic foot infections with special emphasis on the
      appropriate use of surgical interventions and includes the following key
      elements: incision, wound investigation, debridement, wound irrigation and
      lavage, and definitive wound closure.

PMID- 20804937
TI  - Noninvasive assessment of lower extremity hemodynamics in individuals with
      diabetes mellitus.
AB  - The timely and accurate noninvasive assessment of peripheral arterial disease
      (PAD) is a critical component of a limb preservation initiative in patients with
      diabetes mellitus. Noninvasive vascular studies (NIVS) can be useful in screening
      patients with diabetes for PAD. In patients with clinical signs or symptoms, NIVS
      provide crucial information on the presence, location, and severity of PAD, as
      well as an objective assessment of the potential for primary healing of an index
      wound or a surgical incision. Appropriately-selected NIVS are important in the
      decision-making process to determine whether and what type of intervention might
      be most appropriate, given the clinical circumstances. Hemodynamic monitoring is
      likewise very important following either an endovascular procedure or a surgical
      bypass. Surveillance studies, usually with a combination of physiologic testing
      and imaging with duplex ultrasound, accurately identify recurrent disease prior
      to the occurrence of thrombosis, allowing targeted reintervention. NIVS can be
      broadly grouped into three general categories: physiologic or hemodynamic
      measurements; anatomic imaging; and measurements of tissue perfusion. These types
      of tests and suggestions for their appropriate application in patients with
      diabetes are reviewed.

PMID- 20804938
TI  - Arterial imaging in patients with lower extremity ischemia and diabetes mellitus.
AB  - Precise, comprehensive imaging of the arterial circulation is the cornerstone of
      successful revascularization of the ischemic extremity in patients with diabetes
      mellitus. Arterial imaging is challenging in these patients because the disease
      is often multisegmental with a predilection for the distal tibial and peroneal
      arteries. Occlusive lesions and the arterial wall itself are often calcified and
      patients presenting with ischemic complications frequently have underlying renal
      insufficiency. Intra-arterial digital subtraction angiography (DSA), contrast
      enhanced magnetic resonance angiography (MRA), and more recently, computerized
      tomographic angiography (CTA) have been used as imaging modalities in lower
      extremity ischemia. Each has specific advantages and shortcomings in this patient
      population, which will be summarized and contrasted in this review. DSA is an
      invasive technique most often performed from a femoral arterial puncture and
      requires the injection of arterial contrast, which can occasionally cause
      allergic reactions. In patients with pre-existing renal insufficiency, contrast
      infusion can result in worsening renal failure; although usually self-limited, it
      may occasionally require hemodialysis, especially in patients with diabetes.
      However, DSA provides the highest degree of spatial resolution and image quality.
      It is also the only modality in which the diagnosis and treatment of arterial
      disease can be performed simultaneously. MRA is noninvasive, and when enhanced
      with gadolinium contrast injection provides arterial images of comparable quality
      to DSA and in some circumstances may uncover distal arterial targets not
      visualized on DSA. However, spatial resolution is inferior to DSA and erroneous
      interpretations due to acquisition artifacts are common. Specialized equipment
      and imaging techniques are necessary to minimize their occurrence in the distal
      lower extremity. In addition, due to the risk of inducing nephrogenic systemic
      fibrosis, gadolinium-enhanced MRA cannot be used in patients with renal
      insufficiency. CTA is noninvasive and rapidly performed, with better spatial
      resolution than MRA, but requires the largest volume of contrast infusion,
      exposes patients to high-doses of radiation, and is subject to interpretive error
      due to reconstruction artifacts especially in heavily calcified arteries,
      limiting its usefulness in many patients with diabetes. For patients in whom the
      planned intervention is a surgical bypass, DSA and MRA will provide high quality
      images of the lower extremity arterial anatomy. For patients in whom a catheter
      based intervention is the likely treatment, a diagnostic DSA immediately followed
      by a catheter-based treatment in the same procedure is the preferred approach. In
      patients with pre-existing renal dysfunction, in which gadolinium-enhanced MRA is
      contraindicated, DSA or CTA can be performed. However, patients should have an
      infusion of intravenous normal saline solution or sodium bicarbonate before the
      procedure to reduce the incidence of contrast-induced nephropathy.

PMID- 20804939
TI  - Current assessment of endovascular therapy for infrainguinal arterial occlusive
      disease in patients with diabetes.
AB  - Endovascular therapy (EVT) has increasingly become the initial clinical option
      for treatment of lower extremity peripheral arterial disease (PAD), not only for
      patients with claudication, but also for those with critical limb ischemia.
      Despite this major clinical practice paradigm shift, the outcomes of EVT for PAD
      are difficult to evaluate and compare with established surgical benchmarks
      because of the lack of prospective, randomized trials, incomplete
      characterization of indications for intervention, mixing of arterial segments and
      extent of disease treated, the multiplicity of EVT techniques used, the exclusion
      of early treatment failures, crossover to open bypass during follow-up, and the
      frequent lack of intermediate and long-term patency and limb salvage rates in
      life-table format. These data limitations are especially problematic when one
      tries to assess the outcome of EVT in patients with diabetes. The purpose of the
      present report is to succinctly review and objectively analyze available data
      regarding the results of EVT in patients with diabetes.

PMID- 20804940
TI  - Challenges of distal bypass surgery in patients with diabetes: patient selection,
      techniques, and outcomes.
AB  - Surgical revascularization of the lower extremity using bypass grafts to distal
      target arteries is an established, effective therapy for advanced ischemia.
      Recent multicenter data confirm the primacy of autogenous vein bypass grafting,
      yet there remains significant heterogeneity in the utilization, techniques, and
      outcomes associated with these procedures in current practice. Experienced
      clinical judgment, creativity, technical precision, and fastidious postoperative
      care are required to optimize long-term results. The patient with diabetes and a
      critically ischemic limb offers some specific challenges; however, numerous
      studies demonstrate that the outcomes of vein bypass surgery in this population
      are excellent and define the standard of care. Technical factors, such as
      conduit, and inflow/outflow artery selection play a dominant role in determining
      clinical success. An adequate caliber, good quality great saphenous vein (GSV) is
      the optimal graft for distal bypass in the leg. Alternative veins perform
      acceptably in the absence of GSV, whereas prosthetic and other non-autogenous
      conduits have markedly inferior outcomes. Graft configuration (reversed, non
      reversed, or in situ) seems to have little influence on outcome. Shorter grafts
      have improved patency. Inflow can be improved by surgical or endovascular means
      if necessary, and distal-origin grafts (eg, those arising from the superficial
      femoral or popliteal arteries) can perform as well as those originating from the
      common femoral artery. The selected outflow vessel should supply unimpeded runoff
      to the foot, conserve conduit length, allow for adequate soft tissue coverage of
      the graft, and simplified surgical exposure. This review summarizes the available
      data linking patient selection and technical factors to outcomes, and highlights
      the importance of surgical judgment and operative planning in the current
      practice of infrainguinal bypass surgery.

PMID- 20804941
TI  - Should mood during intravenous alcohol administration be studied as a bi- or
      unipolar phenomenon? a pilot study.
AB  - In this study, alcohol was administered intravenously to study whether its
      effects on mood should preferably be studied as a bi- or unipolar phenomenon.
      This was studied in a double-blind, placebo-balanced, design on six healthy male
      volunteers. Of the three bipolar aspects of mood (calmness, activity, and
      pleasantness), only calmness was significantly affected by intravenous alcohol.
      In contrast, there were significant differences between alcohol and placebo for
      five of the six unipolar indexes. This support the hypothesis that subjective
      effects of alcohol on mood are preferably studied with self-ratings that allows
      positive and negative aspects to be analyzed separately. Further, our data
      suggest that the effects of alcohol are primarily on negative aspects of mood
      rather than on positive.

PMID- 20804942
TI  - Phenotype prediction of deleterious nonsynonymous single nucleotide polymorphisms
      in human alcohol metabolism-related genes: a bioinformatics study.
AB  - Nonsynonymous single nucleotide polymorphisms (nsSNPs) are thought as potential
      disease modifiers because they alter the encoded amino acid sequence and are
      likely to affect the function of the proteins accounting for susceptibility to
      disease. Distinguishing the functionally significant nsSNPs from tolerant nsSNPs
      is helpful to characterize the genetic basis of human diseases and assess
      individual susceptibility to diseases. Many nsSNPs have been found in alcohol
      metabolism-related genes but there is poor knowledge on the relationship between
      the genotype and phenotype of nsSNPs in these genes. In this study, we have
      identified a total of 203 nsSNPs in 29 human alcohol metabolism-related genes
      from the National Center for Biotechnology Information (NCBI) dbSNP and SWISS
      Prot databases. Using the PolyPhen and SIFT algorithms, 43% of nsSNPs in alcohol
      metabolism-related genes were predicted to have functional impacts on protein
      function with a significant concordance of the prediction results between the two
      algorithms. The prediction accuracy is about 77-81% of all the nsSNPs based on
      the results of in vivo and in vitro studies. These amino acid substitutions are
      supposed to be the pathogenetic basis for the alteration of metabolism enzyme
      activity and the association with disease susceptivity. The phenotype of nsSNPs
      predicted as deleterious needs to be clarified in further studies and the
      prediction of nsSNPs in human alcohol metabolism-related genes would be useful
      hints for further genotype-phenotype studies on the individual difference in
      susceptivity to alcohol-related diseases.

PMID- 20804944
TI  - Alcohol consumption predicts the EU suicide rates in young women aged 15-29 years
      but not in men: analysis of trends and differences among early and new EU
      countries since 2004.
AB  - The aims of this study were to study suicide rates in youths aged 15-29 years in
      the European Union (EU), to identify differences between early members and new
      members to the EU since 2004, and to evaluate the association between alcohol
      related variables and suicide rates, while controlling for indicators of social
      stress. We explored temporal trends in age-adjusted suicide rates for youths aged
      15-29 years resident in EU nations since 1980. Social changes in EU nations were
      associated with increased inequalities between the countries in suicide,
      especially in male youths (new/early EU members: relative risk=1.55; 95%
      confidence interval: 1.48/1.61). Pure alcohol consumption predicts suicide rates
      in female youths, whereas social stress related to violence against youths
      predicts suicide rates in male youths. EU political and heath agencies should
      devise policies to prevent youth suicide with a focus on alcohol misuse and
      societal stress associated with violence against youths.

PMID- 20804943
TI  - Atrophy of the parahippocampal gyrus and regional cerebral blood flow in the
      limbic system in chronic alcoholic patients.
AB  - This study investigated regional cerebral flood flow (CBF) in chronic alcoholic
      patients, focusing primarily on the limbic system, including the hippocampus and
      the callosomarginal region, because of their susceptibility to damage in such
      patients. The degree of hippocampal atrophy in such patients was also examined.
      Regional CBF and the degree of parahippocampal gyrus atrophy were studied in 22
      chronic alcoholic male patients with no neurological or psychological symptom
      (mean age, 59.3+/-4.1 years). Their findings were compared with those of 22 age
      matched, male, normal controls (mean age, 59.7+/-3.9 years). Single-photon
      emission computed tomography was performed using the (99m)Tc-ethylcysteinate
      dimer ( (99m)Tc-ECD) Patlak Plot method, and the three-dimensional stereotaxic
      region of interest (ROI) template (3DSRT) and the fine stereotaxic ROI template
      (fine SRT) developed by Takeuchi et al were used to evaluate regional CBF,
      focusing primarily on the limbic system. These methods make it possible to
      precisely and objectively measure the details of regional CBF. The voxel-based
      specific regional analysis system for Alzheimer's disease (VSRAD) was used to
      determine the degree of parahippocampal gyrus atrophy in chronic alcoholic
      patients. VSRAD is a method developed by Hirata et al for evaluating the degree
      of atrophy of the parahippocampal gyrus. The results were analyzed using Z scores
      (>2 indicating significant atrophy). Blood flows in the callosomarginal region,
      pericallosal region, thalamus, hippocampus, parahippocampal gyrus, amygdaloid
      body, anterior cingulate gyrus, and middle cingulate gyrus were lower in the
      chronic alcoholic group than in the control group. Parahippocampal gyrus atrophy
      was not observed in the control group (average Z score, 0.62+/-0.29). In
      contrast, an atrophic tendency was observed in the chronic alcoholic group
      (average Z score, 1.88+/-0.44). Clinically intact, chronic alcoholic patients
      with no neurological or psychological symptom had decreased CBF in the limbic
      system and a tendency to parahippocampal gyrus atrophy.

PMID- 20804946
TI  - A right to diapers.

PMID- 20804947
TI  - Including the perspective of the adolescent in palliative care preferences.
AB  - Improving communication with an adolescent with a life-limiting or life
      threatening disease is key to providing comprehensive care and support. A
      pediatric hospital in the Midwest uses a communication tool (CCCT) to facilitate
      conversations about the adolescent's wishes, beliefs, values, preferences and
      goals. Information gathered in a CCCT conversation becomes a key intervention to
      providing compassionate, appropriate care that is directed toward quality of life
      consistent with the adolescent's and family's goals.

PMID- 20804948
TI  - A mentoring program for the promotion of sexual health among Korean adolescents.
AB  - The purpose of this pilot study was to develop a mentoring program for the
      promotion of sexual health among Korean adolescents and to explore the effects of
      the program. A nonequivalent control group pre-test-post-test design was used.
      The mentoring intervention was conducted by eight nursing students who
      participated in the program as mentors using various methods such as formal group
      sessions and informal individual contacts. At the 12-week post-intervention, the
      interaction between time and group was statistically significant on both sexual
      knowledge and sexual attitude of the 17 adolescent mentees. The mentoring program
      demonstrated potential as a developmentally appropriate intervention for the
      sexual health promotion of adolescents and promises to enable nursing students to
      gain confidence in their professional capability.

PMID- 20804949
TI  - Fathers' perspectives on parenting a child with a craniofacial anomaly.
AB  - INTRODUCTION: Although research on healthy children indicates that fathers exert
      specific and beneficial influences on children's development, there is little
      research on fathers of children with chronic medical challenges, and none on
      fathers of children with craniofacial anomalies (CFA). This exploratory study
      aimed to obtain preliminary information about fathers' experiences of parenting a
      child with CFA. METHOD: Structured telephone interviews were conducted with a
      volunteer sample of nine fathers of children with CFA. Interviews were summarized
      using percentages of responses for questions using a rating-scale format, and
      with excerpts of narratives from open-ended questions. RESULTS: Most fathers
      (90%) felt highly optimistic about their children's potential for happiness and
      life success, although a smaller percentage also expressed worry (21% a lot; 33%
      some) and concern (11% a lot; 44% some). All fathers described positive
      attributes in their children. Fathers tended to support their children's peer
      relationships through encouraging and organizing activities with friends.
      DISCUSSION: Fathers' focus on children's effective engagement in the world is
      consistent with findings on fathering of healthy children. Findings provide
      hypotheses for future research on fathers' role in the positive development of
      children with CFA.

PMID- 20804950
TI  - Diagnosing asthma in young children: current research & recommendations.
AB  - Asthma is the leading pediatric chronic illness in the United States, and there
      has been a steady increase in the incidence of asthma in children younger than 6
      years of age. Early intervention for asthma decreases morbidity, controls health
      care costs, and may even preserve lung function. Asthma is difficult to diagnose
      in young children and is under-diagnosed in this population. It is important for
      primary care nurse practitioners to diagnose asthma in young children in a timely
      manner so that therapy can be initiated. This article reviews current
      recommendations for diagnosing asthma in young children and highlights new and
      promising diagnostic tools for asthma.

PMID- 20804951
TI  - Child-feeding practices and child overweight perceptions of family day care
      providers caring for preschool-aged children.
AB  - INTRODUCTION: The purpose of this study was to evaluate the attitudes, feeding
      practices, and child overweight perceptions of family day-care providers caring
      for preschool-aged children and to examine whether child feeding practices differ
      based on child weight perceptions. METHOD: One hundred twenty-three family day
      care providers participated in this cross-sectional exploratory study and
      completed a self-administered survey measuring feeding attitudes and practices
      from the Child Feeding Questionnaire, demographic information, and self-reported
      height and weight. Participants selected a cut point to identify childhood
      overweight using male and female child figure drawings. RESULTS: Participants
      reported a high level of responsibility in feeding and monitoring of children's
      food intake. Differences were found in child feeding practices between family day
      care providers based on their child weight perceptions for girls. Providers who
      selected the smaller girl figures as the cut point for overweight were more
      concerned about the children becoming overweight and used more restriction in
      child feeding compared with the providers who selected the larger girl figures.
      DISCUSSION: Health professionals should continue working with this population to
      promote positive feeding environments.

PMID- 20804952
TI  - The meaning of cost for families of children with congenital heart disease.
AB  - INTRODUCTION: The purpose of this study was to describe the cost burden of
      congenital heart disease (CHD) and the associated social impact as experienced by
      families. METHOD: Qualitative methods were used to collect and interpret data.
      Semi-structured interviews were conducted with parents of children with various
      degrees of CHD complexity and socioeconomic status currently admitted for
      congenital heart surgery at a large tertiary care regional center. RESULTS: The
      meaning of cost burden as defined by participants resulted in the emergence of
      two major categories, lifestyle change and uncertainty. Cost was described beyond
      monetary terms and as a result, data in each category were further clustered into
      three underlying subcategories labeled financial, emotional, and family burden.
      The child's disease complexity and parent's socioeconomic status seem to be
      linked to higher levels of stress experienced in terms of finances, emotional
      drain, and family member burden. Prenatal diagnosis was noted to trigger early
      discussion of financial uncertainty, often resulting in altered personal spending
      prior to birth. DISCUSSION: The cost experienced by parents of children with
      complex CHD was described as both life-changing and uncertain. Informing families
      of these types of additional stressors may allow issues of finances to be
      considered early in the overall preparation of caring for a child with complex
      CHD.

PMID- 20804954
TI  - Pierre Robin sequence: a "Stickler" situation?

PMID- 20804953
TI  - Cerebral sinovenous thrombosis associated with mastoiditis secondary to otitis
      media.

PMID- 20804955
TI  - Attention deficit hyperactivity disorder: Part II.

PMID- 20804956
TI  - Sunscreens: evolving aspects of sun protection.

PMID- 20804957
TI  - Pediatric nurse practitioners as hospitalists.

PMID- 20804958
TI  - The anatomy of survey questions.

PMID- 20804959
TI  - Value-based insurance design: implications for gastroenterology.

PMID- 20804960
TI  - Cancer cell of origin: spotlight on luminal progenitors.

PMID- 20804961
TI  - Microarraying for mechanosensivitity.

PMID- 20804962
TI  - The STATs on naive iPSC reprogramming.

PMID- 20804963
TI  - Hypoxia signaling in hematopoietic stem cells: a double-edged sword.

PMID- 20804965
TI  - The Orphan Drug Act and the development of stem cell-based products for rare
      diseases.
AB  - The Orphan Drug Act encourages the development of products for rare diseases and
      conditions. Many conditions that stand to benefit from stem cell-based products
      are rare diseases. We address the Orphan Drug Act in relation to the development
      of stem cell-based products.

PMID- 20804964
TI  - Tumor-initiating cells are rare in many human tumors.
AB  - Tumor-initiating cells (TICs) are defined by their ability to form tumors after
      xenotransplantation in immunodeficient mice and appear to be relatively rare in
      most human cancers. Recent data in melanoma indicate that the frequency of TICs
      increases dramatically via more permissive xenotransplantation conditions,
      raising the possibility that the true frequency of TICs has been greatly
      underestimated in most human tumors. We compared the growth of human pancreatic,
      non-small cell lung, and head and neck carcinomas in NOD/SCID and NSG mice.
      Although TIC frequency was detected up to 10-fold higher in NSG mice, it remained
      low (<1 in 2500 cells) in all cases. Moreover, aldehyde dehydrogenase-positive
      (ALDH(+)) and CD44(+)CD24(+) cells, phenotypically distinct cells enriched in
      TICs, were equally tumorigenic in NOD/SCID and NSG mice. Our findings demonstrate
      that TICs are rare in these cancers and that the identification of TICs and their
      frequency in other human malignancies should be validated via primary tumors and
      highly permissive xenotransplantation conditions.

PMID- 20804966
TI  - Polycomb group proteins set the stage for early lineage commitment.
AB  - Precise control of gene expression patterns is critical for the specification of
      cellular diversity during metazoan development. Polycomb group (PcG) proteins
      comprise a class of transcriptional modifiers that have dynamic and essential
      roles in regulating a number of key processes including lineage commitment. How
      this is accomplished during mammalian development is incompletely understood.
      Here, we discuss recent studies in embryonic stem cells (ESCs) that provide
      critical new insights into how PcG proteins may be targeted to genomic sites as
      well as the mechanisms by which these regulators influence gene expression and
      multilineage differentiation in mammals.

PMID- 20804968
TI  - Toward a knowledge of causes.

PMID- 20804967
TI  - Polycomb group proteins: multi-faceted regulators of somatic stem cells and
      cancer.
AB  - Polycomb Group (PcG) proteins are transcriptional repressors that epigenetically
      modify chromatin and participate in the establishment and maintenance of cell
      fates. These proteins play important roles in both stem cell self-renewal and in
      cancer development. Our understanding of their mechanism of action has greatly
      advanced over the past 10 years, but many unanswered questions remain. In this
      review, we present the currently available experimental data that connect PcG
      protein function with some of the key processes which govern somatic stem cell
      activity. We also highlight recent studies suggesting that a delicate balance in
      PcG gene dosage is crucial for proper stem cell homeostasis and prevention of
      cancer stem cell development.

PMID- 20804969
TI  - Stat3 activation is limiting for reprogramming to ground state pluripotency.
AB  - The cytokine leukemia inhibitory factor (Lif) sustains self-renewal of mouse
      embryonic and induced pluripotent stem cells by activating Jak kinase and the
      transcription factor Stat3. Here we investigate whether Jak/Stat3 may also
      contribute to induction of pluripotency. EpiSCs derived from postimplantation
      embryos express low levels of Lif receptor and Stat3. We introduced into EpiSCs a
      Jak/Stat3 activating receptor (GY118F) responsive to granulocyte colony
      stimulating factor (Gcsf). On transfer to ground state culture, in which MAPK
      signaling and glycogen synthase kinase are inhibited, Gcsf induced
      transcriptional resetting and functional reprogramming. Activation of a tamoxifen
      regulatable fusion, Stat3ER(T2), also converted EpiSCs into chimera-competent
      iPSCs. We exploited GY118F to increase Jak/Stat3 activity during somatic cell
      reprogramming. Incompletely reprogrammed cells derived from neural stem cells or
      fibroblasts responded to Gcsf with elevated frequencies of progression to ground
      state pluripotency. These findings indicate that Jak/Stat3 participate directly
      in molecular reprogramming and that activation of this pathway is a limiting
      component.

PMID- 20804970
TI  - Myc represses primitive endoderm differentiation in pluripotent stem cells.
AB  - The generation of induced pluripotent stem cells (iPSCs) provides a novel method
      to facilitate investigations into the mechanisms that control stem cell
      pluripotency and self-renewal. Myc has previously been shown to be critical for
      murine embryonic stem cell (mESC) maintenance, while also enhancing directed
      reprogramming of fibroblasts by effecting widespread changes in gene expression.
      Despite several studies identifying in vivo target genes, the precise mechanism
      by which Myc regulates pluripotency remains unknown. Here we report that
      codeletion of c- and N-MYC in iPSCs and ESCs results in their spontaneous
      differentiation to primitive endoderm. We show that Myc sustains pluripotency
      through repression of the primitive endoderm master regulator GATA6, while also
      contributing to cell cycle control by regulation of the mir-17-92 miRNA cluster.
      Our findings demonstrate the indispensable requirement for c- or N-myc in
      pluripotency beyond proliferative and metabolic control.

PMID- 20804971
TI  - Functional diversity of ESC-derived motor neuron subtypes revealed through
      intraspinal transplantation.
AB  - Cultured ESCs can form different classes of neurons, but whether these neurons
      can acquire specialized subtype features typical of neurons in vivo remains
      unclear. We show here that mouse ESCs can be directed to form highly specific
      motor neuron subtypes in the absence of added factors, through a differentiation
      program that relies on endogenous Wnts, FGFs, and Hh-mimicking the normal program
      of motor neuron subtype differentiation. Molecular markers that characterize
      motor neuron subtypes anticipate the functional properties of these neurons in
      vivo: ESC-derived motor neurons grafted isochronically into chick spinal cord
      settle in appropriate columnar domains and select axonal trajectories with a
      fidelity that matches that of their in vivo generated counterparts. ESC-derived
      motor neurons can therefore be programmed in a predictive manner to acquire
      molecular and functional properties that characterize one of the many dozens of
      specialized motor neuron subtypes that exist in vivo.

PMID- 20804972
TI  - Regulated segregation of kinase Dyrk1A during asymmetric neural stem cell
      division is critical for EGFR-mediated biased signaling.
AB  - Stem cell division can result in two sibling cells exhibiting differential
      mitogenic and self-renewing potential. Here, we present evidence that the dual
      specificity kinase Dyrk1A is part of a molecular pathway involved in the
      regulation of biased epidermal growth factor receptor (EGFR) signaling in the
      progeny of dividing neural stem cells (NSC) of the adult subependymal zone (SEZ).
      We show that EGFR asymmetry requires regulated sorting and that a normal Dyrk1a
      dosage is required to sustain EGFR in the two daughters of a symmetrically
      dividing progenitor. Dyrk1A is symmetrically or asymmetrically distributed during
      mitosis, and biochemical analyses indicate that it prevents endocytosis-mediated
      degradation of EGFR by a mechanism that requires phosphorylation of the EGFR
      signaling modulator Sprouty2. Finally, Dyrk1a heterozygous NSCs exhibit defects
      in self-renewal, EGF-dependent cell-fate decisions, and long-term persistence in
      vivo, suggesting that symmetrical divisions play a role in the maintenance of the
      SEZ reservoir.

PMID- 20804973
TI  - The distinct metabolic profile of hematopoietic stem cells reflects their
      location in a hypoxic niche.
AB  - Bone marrow transplantation is the primary therapy for numerous hematopoietic
      disorders. The efficiency of bone marrow transplantation depends on the function
      of long-term hematopoietic stem cells (LT-HSCs), which is markedly influenced by
      their hypoxic niche. Survival in this low-oxygen microenvironment requires
      significant metabolic adaptation. Here, we show that LT-HSCs utilize glycolysis
      instead of mitochondrial oxidative phosphorylation to meet their energy demands.
      We used flow cytometry to identify a unique low mitochondrial activity/glycolysis
      dependent subpopulation that houses the majority of hematopoietic progenitors and
      LT-HSCs. Finally, we demonstrate that Meis1 and Hif-1alpha are markedly enriched
      in LT-HSCs and that Meis1 regulates HSC metabolism through transcriptional
      activation of Hif-1alpha. These findings reveal an important transcriptional
      network that regulates HSC metabolism.

PMID- 20804974
TI  - Regulation of the HIF-1alpha level is essential for hematopoietic stem cells.
AB  - Hematopoietic stem cells (HSCs) are sustained in a specific microenvironment
      known as the stem cell niche. Mammalian HSCs are kept quiescent in the endosteal
      niche, a hypoxic zone of the bone marrow (BM). In this study, we show that normal
      HSCs maintain intracellular hypoxia and stabilize hypoxia-inducible factor-1alpha
      (HIF-1alpha) protein. In HIF-1alpha-deficient mice, the HSCs lost their cell
      cycle quiescence and HSC numbers decreased during various stress settings
      including bone marrow transplantation, myelosuppression, or aging, in a
      p16(Ink4a)/p19(Arf)-dependent manner. Overstabilization of HIF-1alpha by
      biallelic loss of an E3 ubiquitin ligase for HIF-1alpha (VHL) induced cell cycle
      quiescence in HSCs and their progenitors but resulted in an impairment in
      transplantation capacity. In contrast, monoallelic loss of VHL induced cell cycle
      quiescence and improved BM engraftment during bone marrow transplantation. These
      data indicate that HSCs maintain cell cycle quiescence through the precise
      regulation of HIF-1alpha levels.

PMID- 20804975
TI  - BRCA1 basal-like breast cancers originate from luminal epithelial progenitors and
      not from basal stem cells.
AB  - Breast cancers in BRCA1 mutation carriers frequently have a distinctive basal
      like phenotype. It has been suggested that this results from an origin in basal
      breast epithelial stem cells. Here, we demonstrate that deleting Brca1 in mouse
      mammary epithelial luminal progenitors produces tumors that phenocopy human BRCA1
      breast cancers. They also resemble the majority of sporadic basal-like breast
      tumors. However, directing Brca1 deficiency to basal cells generates tumors that
      express molecular markers of basal breast cancers but do not histologically
      resemble either human BRCA1 or the majority of sporadic basal-like breast tumors.
      These findings support a derivation of the majority of human BRCA1-associated and
      sporadic basal-like tumors from luminal progenitors rather than from basal stem
      cells. They also demonstrate that when target cells for transformation have the
      potential for phenotypic plasticity, tumor phenotypes may not directly reflect
      histogenesis. This has important implications for cancer prevention strategies.

PMID- 20804976
TI  - Synthesis of the pentasaccharide repeating unit of Escherichia coli O128 antigen.
AB  - A pentasaccharide, 4-methoxyphenyl 2-acetamido-2-deoxy-beta-d-galactopyranosyl-(1
      >4)-alpha-d-galactopyranosyl-(1->3)-2-acetamido-2-deoxy-beta-d-galactopyranosyl
      (1->6)-[alpha-l-fucopyranosyl-(1->2)]-beta-d-galactopyranoside (1), representing
      the repeating unit of Escherichia coli O128 antigen, was successfully prepared in
      23% overall yield via a convergent '2+3' glycosylation strategy.

PMID- 20804977
TI  - Auditory adaptation in vocal affect perception.
AB  - Previous research has demonstrated perceptual aftereffects for emotionally
      expressive faces, but the extent to which they can also be obtained in a
      different modality is unknown. In two experiments we show for the first time that
      adaptation to affective, non-linguistic vocalisations elicits significant
      auditory aftereffects. Adaptation to angry vocalisations caused voices drawn from
      an anger-fear morphed continuum to be perceived as less angry and more fearful,
      while adaptation to fearful vocalisations elicited opposite aftereffects
      (Experiment 1). We then tested the link between these aftereffects and the
      underlying acoustics by using caricatured adaptors. Although caricatures
      exaggerated the acoustical and affective properties of the vocalisations, the
      caricatured adaptors resulted in aftereffects which were comparable to those
      obtained with natural vocalisations (Experiment 2). Our findings suggest that
      these aftereffects cannot be solely explained by low-level adaptation to
      acoustical characteristics of the adaptors but are likely to depend on higher
      level adaptation of neural representations of vocal affect.

PMID- 20804978
TI  - Enhanced memory for the wolf in sheep's clothing: facial trustworthiness
      modulates face-trait associative memory.
AB  - Our decision about whether to trust and cooperate with someone is influenced by
      the individual's facial appearance despite its limited predictive power. Thus,
      remembering trustworthy-looking cheaters is more important than remembering
      untrustworthy-looking cheaters because we are more likely to trust and cooperate
      with the former, resulting in a higher risk of unreciprocated cooperation. The
      present study investigated whether our mind adaptively copes with this problem by
      enhancing memory for trustworthy-looking cheaters. Participants played a debt
      game, wherein they learned to discriminate among good, neutral, and bad lenders,
      who respectively charged no, moderate, and high interest on the debt. Each lender
      had either a trustworthy- or untrustworthy-looking face. A subsequent memory test
      revealed that participants remembered the bad traits of trustworthy-looking
      lenders more accurately than those of untrustworthy-looking lenders. The results
      demonstrate enhanced memory for trustworthy-looking cheaters, or wolves in
      sheep's clothing, implying that humans are equipped with protective mechanisms
      against disguised, unfaithful signs of trustworthiness.

PMID- 20804980
TI  - LAN attack detection using Discrete Event Systems.
AB  - Address Resolution Protocol (ARP) is used for determining the link layer or
      Medium Access Control (MAC) address of a network host, given its Internet Layer
      (IP) or Network Layer address. ARP is a stateless protocol and any IP-MAC pairing
      sent by a host is accepted without verification. This weakness in the ARP may be
      exploited by malicious hosts in a Local Area Network (LAN) by spoofing IP-MAC
      pairs. Several schemes have been proposed in the literature to circumvent these
      attacks; however, these techniques either make IP-MAC pairing static, modify the
      existing ARP, patch operating systems of all the hosts etc. In this paper we
      propose a Discrete Event System (DES) approach for Intrusion Detection System
      (IDS) for LAN specific attacks which do not require any extra constraint like
      static IP-MAC, changing the ARP etc. A DES model is built for the LAN under both
      a normal and compromised (i.e., spoofed request/response) situation based on the
      sequences of ARP related packets. Sequences of ARP events in normal and spoofed
      scenarios are similar thereby rendering the same DES models for both the cases.
      To create different ARP events under normal and spoofed conditions the proposed
      technique uses active ARP probing. However, this probing adds extra ARP traffic
      in the LAN. Following that a DES detector is built to determine from observed ARP
      related events, whether the LAN is operating under a normal or compromised
      situation. The scheme also minimizes extra ARP traffic by probing the source IP
      MAC pair of only those ARP packets which are yet to be determined as
      genuine/spoofed by the detector. Also, spoofed IP-MAC pairs determined by the
      detector are stored in tables to detect other LAN attacks triggered by spoofing
      namely, man-in-the-middle (MiTM), denial of service etc. The scheme is
      successfully validated in a test bed.

PMID- 20804979
TI  - Is the word-length effect linked to subvocal rehearsal?
AB  - Models of phonological short-term memory (pSTM) generally distinguish between two
      components: a phonological buffer and a subvocal rehearsal. Evidence for these
      two components comes, respectively, from the phonological similarity effect and
      the word-length effect which disappears under articulatory suppression. But
      alternative theories posit that subvocal rehearsal is only an optional component
      of the pSTM. According to them, the depletion of the length effect under
      articulatory suppression results from the interference of the self-produced
      speech rather than the disruption of subvocal rehearsal. In order to disentangle
      these two theories, we tested two patients with a short-term memory deficit. FA,
      who presents a pseudoword repetition deficit, and FL, who does not. FA's deficit
      allowed for the observance of an ecological case of subvocal rehearsal disruption
      without any articulatory suppression task. FA's performance in pSTM tasks reveals
      as controls a phonological similarity effect, and contrary to controls no word
      length effect. In contrast, the second patient, FL, exhibits the same effects as
      control subjects. This result is in accordance with models of pSTM in which the
      word-length effect emerges from subvocal rehearsal and disappears when this
      latter is disrupted.

PMID- 20804981
TI  - Effect of adsorbed/intercalated anionic dyes into the mechanical properties of
      PVA: layered zinc hydroxide nitrate nanocomposites.
AB  - Zinc hydroxide nitrate (ZHN) was adsorbed with anions of blue dyes (Chicago sky
      blue, CSB; Evans blue, EB; and Niagara blue, NB) and intercalated with anions of
      orange dyes (Orange G, OG; Orange II, OII; methyl orange, MO). Transparent,
      homogeneous and colored nanocomposite films were obtained by casting after
      dispersing the pigments (dye-intercalated/adsorbed into LHSs) into commercial
      poly(vinyl alcohol) (PVA). The films were characterized by XRD, UV-Vis
      spectroscopy, and mechanical testing. The mechanical properties of the PVA
      compounded with the dye-intercalated/adsorbed ZHN were evaluated, and reasonable
      increases in Young's modulus and ultimate tensile strength were observed,
      depending on the amount and choice of layered filler. These results demonstrate
      the possibility of using a new class of layered hydroxide salts intercalated and
      adsorbed with anionic dyes to prepare multifunctional polymer nanocomposite
      materials.

PMID- 20804982
TI  - Effect of surfactants on interfacial films and stability of water-in-oil
      emulsions stabilized by asphaltenes.
AB  - The effect of additives on asphaltene interfacial films and emulsion stability
      was analyzed through the change in film properties. Surface pressure isotherms
      were measured at 23 degrees C for model interfaces between aqueous surfactant
      solutions and asphaltenes dissolved in toluene and heptane-toluene mixtures.
      Compressibility, crumpling film ratio and surface pressure were determined from
      the surface pressure isotherms. The stability of water-in-oil emulsions was
      determined for the same systems based on the proportion of unresolved emulsified
      water after repeated treatment involving heating at 60 degrees C and
      centrifugation. Experimental variables included concentration of asphaltenes (5
      and 10 kg/m(3)), concentration and type of surfactant (Aerosol OT, nonylphenol
      ethoxylates, polypropylene oxide block-copolymer, dodecylbenzene sulfonic acids,
      dodecylbenzene sulfonic acid-polymer blend, diisopropyl naphthalene sulfonic
      acid, and sodium naphthenate) and aging time (from 10 min to 4 h). Additives were
      found to have two opposing effects on film properties and emulsion stability: (1)
      decreasing or eliminating the crumpling ratio which destabilized emulsions and
      (2) decreasing interfacial tension which enhanced emulsion stability. A stability
      parameter was defined to include both the crumpling ratio and interfacial tension
      and provided a consistent correlation for the percent residual emulsified water.

PMID- 20804983
TI  - In situ ATR-FTIR studies on the competitive adsorption of arsenate and phosphate
      on ferrihydrite.
AB  - In the present study, in situ ATR-FTIR spectroscopy was used for the first time
      to study the competitive adsorption of phosphate and arsenate on ferrihydrite.
      Deuterium oxide was used as solvent to facilitate the interpretations of recorded
      infrared spectra. It was found that arsenate and phosphate adsorbed more strongly
      at lower pD-values, showing similarities in the adsorption behavior as a function
      of pD. However, arsenate complexes were found to be more strongly adsorbed than
      phosphate complexes in the pD range studied. About five times higher
      concentration of phosphate in solution was needed to reduce the absorbance due to
      pre-adsorbed arsenate to the same relative level as for pre-adsorbed phosphate,
      which was desorbed using a solution containing equal (molar) concentrations in
      arsenate and phosphate. At pD 4, two phosphate complexes were adsorbed on the
      iron oxide, one deuterated and one de-deuterated. When phosphate was pre-adsorbed
      and arsenate subsequently added to the system, the deuterated phosphate complex
      desorbed rapidly while the de-deuterated phosphate complex was quite stable. At
      pD 8.5, only the de-deuterated phosphate complex was adsorbed on the iron oxide.
      Moreover, the arsenate adsorbed was also predominantly de-deuterated as opposite
      to the arsenate adsorbed at pD 4. During the substitution experiments the
      configuration of these complexes on the iron oxide surface did not change. To the
      best of our knowledge, this is the first time this difference in stability of the
      different phosphate complexes is reported and shows the power of employing in
      situ spectroscopy for this kind of studies.

PMID- 20804984
TI  - Acoustophoresis in shallow microchannels.
AB  - Acoustophoretic (AP) motion of spherical polystyrene particles in a steady
      pressure driven flow is investigated in shallow microchannels, where the channel
      height is comparable to the particle diameter. Particle trajectories at different
      ultrasonic actuation amplitudes are extracted by a particle tracking algorithm.
      Depths of the particles are predicted using the streamwise particle speed that is
      due to the pressure driven flow. The particle depths are shown to be influenced
      by the actuation voltage. The particle migration along the channel height is
      explained using the second-order perturbation theory. The particle equation of
      motion is employed to extract the AP force. Wall effects are included in the
      analysis of both particle depth and force predictions. Differences as large as
      20% in the AP force magnitude due to the wall corrections are reported. The AP
      force is also calculated using the theoretical force expression, and compared
      with the experimental results. The focal length, which is the necessary distance
      to effectively concentrate particles in a microchannel, is calculated using the
      analytical solution of the particle equation of motion. The calculated force and
      the focusing length agree well with the experimental results. The focal length is
      critical for the design of micro sample concentration devices.

PMID- 20804985
TI  - Controllable synthesis, characterization and optical properties of colloidal
      PbS/gelatin core-shell nanocrystals.
AB  - Native quantum dots (QDs) made up of semiconductor nanocrystals (NCs) are toxic
      in nature but due to their excellent optical properties, they have proven
      themselves to be an attractive choice in biological labeling and targeting. In
      order to improve the general biocompatibility of lead sulfide (PbS) NCs, we
      present a new and simple procedure for preparing PbS/gelatin core-shell
      nanoparticles cross-linked with glutaraldehyde (GA) molecules. The phase
      composition, morphology, luminescence and in vitro photostability of the samples
      were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR),
      transmission electron microscope (TEM) and fluorescence spectroscopy,
      respectively. The XRD analysis showed that the PbS NCs were of the cubic
      structure, the mean crystallite size was calculated to be 13.5 nm and the
      calculated lattice constant using Bragg's equation was 0.5950 nm, which was very
      close to its value in the standard card (JCPDS No. 5-592). In vitro test revealed
      that compared with bare PbS NCs, the photostability of the core-shell
      nanostructure remarkably improved. In addition, possible formation mechanisms of
      the PbS/gelatin nanoparticles were discussed in detail. Consequently, the
      advantages of high stability as well as high fluorescent intensity and
      biocompatibility make the core-shell nanoparticles promising candidates for in
      vivo biological targeting applications.

PMID- 20804986
TI  - Deficits in stepping response time are associated with impairments in balance and
      mobility in people with Huntington disease.
AB  - Huntington disease (HD) is a disorder characterized by chorea, dystonia,
      bradykinesia, cognitive decline and psychiatric comorbidities. Balance and gait
      impairments, as well as falls, are common manifestations of the disease. The
      importance of compensatory rapid stepping to maintain equilibrium in older adults
      is established, yet little is known of the role of stepping response times (SRTs)
      in balance control in people with HD. SRTs and commonly-used clinical measures of
      balance and mobility were evaluated in fourteen symptomatic participants with HD,
      and nine controls at a university mobility research laboratory. Relative and
      absolute reliability, as well as minimal detectable change in SRT were quantified
      in the HD participants. HD participants exhibited slower SRTs and poorer dynamic
      balance, mobility and motor performance than controls. HD participants also
      reported lower balance confidence than controls. Deficits in SRT were associated
      with low balance confidence and impairments on clinical measures of balance,
      mobility, and motor performance in HD participants. Measures of relative and
      absolute reliability indicate that SRT is reliable and reproducible across trials
      in people with HD. A moderately low percent minimal detectable change suggests
      that SRT appears sensitive to detecting real change in people with HD. SRT is
      impaired in people with HD and may be a valid and objective marker of disease
      progression.

PMID- 20804987
TI  - Subjective and objective assessment of fatigue.

PMID- 20804988
TI  - Temporal trends and geographic clusters of mortality from amyotrophic lateral
      sclerosis in Japan, 1995-2004.
AB  - The present study examined temporal trends and geographic clustering of
      amyotrophic lateral sclerosis (ALS) mortality in Japan, during 1995-2004, using
      vital statistics based on death certificates. ALS was usually diagnosed by
      neurologists according to clinical guidelines that complied with the El Escorial
      Criteria. The underlying cause of death for ALS was coded as G12.2A. Regression
      analysis was used to examine temporal trends. Spatial scan statistic was used to
      detect any area of elevated risk as a cluster. A total of 12,173 (6864 male and
      5309 female) ALS deaths were reported. Annual crude mortality rate per 100,000
      population was 1.07 (1.26 for males and 0.89 for females) in 2004. Although the
      overall temporal trend was stable, the trend increased in the 70+ years age group
      (p for trend, <0.001 in males and <0.05 in females), while it declined in the
      under 70 years age group (p for trend, <0.01 for both sexes). Male preponderance
      and M/F ratio remained nearly constant over time. Three clusters were detected:
      two (p<0.005 in males and p<0.05 in females) in northeast and one (p<0.05 in
      males) in west-central Japan. Further research is needed to clarify contributing
      factors for the observed trends and clusters in ALS mortality.

PMID- 20804990
TI  - Diazoxide maintenance of myocyte volume and contractility during stress: evidence
      for a non-sarcolemmal K(ATP) channel location.
AB  - OBJECTIVE: Animal and human myocytes demonstrate significant swelling and reduced
      contractility during exposure to stress (metabolic inhibition, hyposmotic stress,
      or hyperkalemic cardioplegia), and these detrimental consequences may be
      inhibited by the addition of diazoxide (adenosine triphosphate-sensitive
      potassium channel opener) via an unknown mechanism. Both SUR1 and SUR2A subunits
      have been localized to the heart, and mouse sarcolemmal adenosine triphosphate
      sensitive potassium channels are composed of SUR2A/Kir6.2 subunits in the
      ventricle and SUR1/Kir6.2 subunits in the atria. This study was performed to
      localize the mechanism of diazoxide by direct probing of sarcolemmal adenosine
      triphosphate-sensitive potassium channel current and by genetic deletion of
      channel subunits. METHODS: Sarcolemmal adenosine triphosphate-sensitive potassium
      channel current was recorded in isolated wild-type ventricular mouse myocytes
      during exposure to Tyrode's solution, Tyrode's + 100 MUmol/L diazoxide,
      hyperkalemic cardioplegia, cardioplegia + diazoxide, cardioplegia + 100 MUmol/L
      pinacidil, or metabolic inhibition using whole-cell voltage clamp (N = 7-12 cells
      per group). Ventricular myocyte volume was measured from SUR1(-/-) and wild-type
      mice during exposure to control solution, hyperkalemic cardioplegia, or
      cardioplegia + 100 MUmol/L diazoxide (N = 7-10 cells per group). RESULTS:
      Diazoxide did not increase sarcolemmal adenosine triphosphate-sensitive potassium
      current in wild-type myocytes, although they demonstrated significant swelling
      during exposure to cardioplegia that was prevented by diazoxide. SUR1(-/-)
      myocytes also demonstrated significant swelling during exposure to cardioplegia,
      but this was not altered by diazoxide. CONCLUSIONS: Diazoxide does not open the
      ventricular sarcolemmal adenosine triphosphate-sensitive potassium channel but
      provides volume homeostasis via an SUR1-dependent pathway in mouse ventricular
      myocytes, supporting a mechanism of action distinct from sarcolemmal adenosine
      triphosphate-sensitive potassium channel activation.

PMID- 20804992
TI  - General thoracic surgery is safe in patients taking clopidogrel (Plavix).
AB  - BACKGROUND: The objective of this study was to assess the safety of general
      thoracic surgery in patients taking antiplatelet (clopidogrel) therapy. METHODS:
      A prospective study was conducted of consecutive patients who underwent general
      thoracic surgery and who were taking clopidogrel perioperatively. They were
      matched using a propensity score from our prospective database of 11,768
      patients. Intraoperative and postoperative outcomes were compared. RESULTS:
      Between January 2009 and April 2010 there were 33 patients on clopidogrel at the
      time of surgery and 132 controls. The most common procedures were thoracotomy
      with lobectomy in 11 patients (robotic in 1), video-assisted wedge resection in
      6, mediastinoscopy in 4, and Ivor Lewis esophagogastrectomy in 2. Epidurals were
      not used. There was no intraoperative morbidity or bleeding in primary
      thoracotomy; however, 2 of the 4 patients who underwent redo thoracotomy had
      bleeding that required transfusions. None of the 8 patients receiving clopidogrel
      who had a coronary artery stent and underwent lobectomy had a perioperative
      myocardial infarction whereas 5 of the 14 control patients undergoing lobectomy
      who had a coronary artery stent did (P = .05). Otherwise, morbidity, mortality,
      and length of stay were no different. CONCLUSIONS: Patients who are receiving
      clopidogrel and who have a coronary artery stent placed can safely undergo
      general thoracic surgery. The widely held belief that surgery cannot be performed
      without bleeding is untrue. This new finding not only eliminates much of the
      preoperative dilemma posed by these patients but also may reduce their risk of a
      postoperative myocardial infarction. However, patients who require a redo
      thoracotomy may be at increased risk of bleeding.

PMID- 20804993
TI  - Effects of selective cyclooxygenase-2 and nonselective cyclooxygenase inhibition
      on ischemic myocardium.
AB  - OBJECTIVE: We explored effects of nonselective cyclooxygenase and selective
      cyclooxygenase 2 inhibition on collateral development in a model of chronic
      myocardial ischemia. We hypothesized that cyclooxygenase 2 inhibitors would
      negatively effect angiogenic and inflammatory pathways. METHODS: Yorkshire swine
      were made chronically ischemic by placing an ameroid constrictor on the left
      circumflex coronary artery. Swine were divided into 3 groups and given no drug
      (control, n = 7), a nonselective cyclooxygenase inhibitor (naproxen 400 mg daily,
      n = 7), or a selective cyclooxygenase 2 inhibitor (celecoxib 200 mg daily, n =
      7). After 7 weeks, coronary angiography was performed. Myocardial function and
      microvascular reactivity were assessed. Serum and myocardial tissue were analyzed
      for prostaglandin levels and markers of inflammation and angiogenesis. RESULTS:
      The celecoxib group demonstrated significantly increased mean arterial pressure
      and decreased left ventricular function. Myocardial perfusion in the celecoxib
      group was similar to control value but less than in the naproxen group. Coronary
      microvascular contraction in the collateral-dependent territory was increased in
      the naproxen group but minimally affected in the celecoxib group. Oxidative
      stress and apoptosis were increased in the celecoxib group. Expression of
      angiogenic markers vascular endothelial growth factor and phospho-endothelial
      nitric oxide synthase (ser1177) and tissue levels of prostacyclin were decreased
      in both celecoxib and naproxen groups. The naproxen group had diminished
      endostatin expression. CONCLUSIONS: Selective and nonselective cyclooxygenase
      inhibition are more complex in effect than previously published, but they did not
      decrease collateral-dependent blood flow to the myocardium in our model of
      chronic myocardial ischemia.

PMID- 20804996
TI  - Specificity of DNA sequences recognized by the zinc-finger homeodomain protein,
      GmZF-HD1 in soybean.
AB  - Zinc finger-homeodomain proteins (ZF-HDs) have been identified in many plant
      species. In soybean (Glycine max), GmZF-HD1 functions as a transcription factor
      that activates the soybean calmodulin isoform-4 (GmCaM-4) gene in response to
      pathogens. Recently, we reported specific binding of GmZF-HD1 to a 30-nt A/T-rich
      cis-element which constitutes two repeats of a conserved homeodomain binding
      site, ATTA, within -1207 to -1128bp of the GmCaM-4 promoter. Herein, homeodomain
      sequences of the GmZF-HD1 protein were compared to those of other homeodomain
      proteins and characterized the specificity of DNA sequences in the interaction of
      the GmCaM-4 promoter with GmZF-HD1 protein. Considering the conservation of
      homeodomains in plants, the AG sequence within a 30-nt A/T-rich cis-element is
      required for binding of the GmZF-HD1 protein. Approximately 25-bp of A/T-rich DNA
      sequences containing an AG sequence is necessary for effective binding to the
      GmZF-HD1 protein. Taken together, the results support the notion that the GmZF
      HD1 protein specifically functions in plant stress signalling by interacting with
      the promoter of GmCaM-4.

PMID- 20804997
TI  - Application of ultrasound in electrochemistry. An overview of mechanisms and
      design of experimental arrangement.
AB  - An overview of possible mechanisms by which sonication can influence
      electrochemical processes is given. Four mechanisms are discussed: - acoustic
      streaming; - microstreaming and turbulence due to cavitation; - formation of
      microjets in the course of collapse of cavitation bubble; - shock waves; and
      possible effects are illustrated on several examples. The most effective process
      is formation of microjets,which can not only decrease diffusion layer thickness
      under 1 lm, but also activate (depassivate) electrode surface. Design of
      experimental arrangement with maximum participation of microjets is proposed. Two
      approaches are proposed: - focusing of ultrasound on the working electrode and
      reduction of energy losses by over-pressure; - ''tuning" the reactor to obtain
      resonance, i.e. formation of stationary waves by activating reactor in
      itsresonant mode.

PMID- 20804998
TI  - Fate of aromatic hydrocarbons in Italian municipal wastewater systems: an
      overview of wastewater treatment using conventional activated-sludge processes
      (CASP) and membrane bioreactors (MBRs).
AB  - We studied the occurrence, removal, and fate of 16 polycyclic aromatic
      hydrocarbons (PAHs) and 23 volatile organic compounds (VOCs) in Italian municipal
      wastewater treatment systems in terms of their common contents and forms, and
      their apparent and actual removal in both conventional activated-sludge processes
      (CASP) and membrane bioreactors (MBRs). We studied five representative full-scale
      CASP treatment plants (design capacities of 12,000 to 700,000 population
      equivalent), three of which included MBR systems (one full-scale and two pilot
      scale) operating in parallel with the conventional systems. We studied the solid
      liquid partitioning and fates of these substances using both conventional samples
      and a novel membrane-equipped automatic sampler. Among the VOCs, toluene,
      ethylbenzene, xylenes, styrene, 1,2,4-trimethylbenzene, and 4-chlorotoluene were
      ubiquitous, whereas naphthalene, acenaphthene, fluorene, and phenanthrene were
      the most common PAHs. Both PAHs and aromatic VOCs had removal efficiencies of 40
      60% in the headworks, even in plants without primary sedimentation. Mainly due to
      volatilization, aromatic VOCs had comparable removal efficiencies in CASP and
      MBRs, even for different sludge ages. MBRs did not enhance the retention of PAHs
      sorbed to suspended particulates compared with CASPs. On the other hand, the
      specific daily accumulation of PAHs in the MBR's activated sludge decreased
      logarithmically with increasing sludge age, indicating enhanced biodegradation of
      PAHs. The PAH and aromatic VOC contents in the final effluent are not a major
      driver for widespread municipal adoption of MBRs, but MBRs may enhance the
      biodegradation of PAHs and their removal from the environment.

PMID- 20804999
TI  - Photochemical analysis of 14C-fenhexamid in aqueous solution and structural
      elucidation of a new metabolite.
AB  - The photodegradation kinetics and the break down pathway of fenhexamid were
      studied in aqueous systems using [phenyl-UL-14C]- and [carbonyl-14C]-labelled
      compounds. The photolysis of fenhexamid followed first-order kinetics. The
      degradation rate of fenhexamid was significantly influenced by the solution pH
      with rate constants (k) of 2.11*10(-2), 4.47*10(-2), 6.11*10(-1) and 1.69 h(-1)
      at pH 5.0, 6.6, 7.3 and 9.0, respectively. Fenhexamid exhibited no significant
      change in degradation rate in the presence of acetone and hydrogen peroxide,
      while humic and fulvic acids retarded the degradation rate, because they shielded
      the active molecules from light. However, in phosphate medium, the photolysis
      rate was significantly enhanced as a function of concentration. About 3-8% and 10
      25% photo mineralization were observed, using [carbonyl-14C]- and [phenyl-UL-14C]
      labelled fenhexamid in aqueous solutions at different pH, respectively. In
      addition to four known metabolites, one major and five minor photoproducts out of
      which one is reported for the first time, were identified using high resolution
      LC-MS/MS and NMR. The toxicity of the new metabolite was tested against the fish
      Oncorhynchus mykiss with no lethal effect at 100 mg L(-1).

PMID- 20805000
TI  - Emergy analysis of an industrial park: the case of Dalian, China.
AB  - With the rapid development of eco-industrial park projects in China, evaluating
      their overall eco-efficiency is becoming an important need and a big challenge
      academically. Developing ecologically conscious industrial park management
      requires analysis of both industrial and ecological systems. Traditional
      evaluation methods based on neoclassical economics and embodied energy and exergy
      analyses have certain limitations due to their focus with environmental issues
      considered secondary to the maximization of economic and technical objectives.
      Such methods focus primarily on the environmental impact of emissions and their
      economic consequences. These approaches ignore the contribution of ecological
      products and services as well as the load placed on environmental systems and
      related problems of carrying capacity of economic and industrial development.
      This paper presents a new method, based upon emergy analysis and synthesis. Such
      a method links economic and ecological systems together, highlighting the
      internal relations among the different subsystems and components. The emergy
      based method provides insight into the environmental performance and
      sustainability of an industrial park. This paper depicts the methodology of
      emergy analysis at the industrial park level and provides a series of emergy
      based indices. A case study is investigated and discussed in order to show the
      emergy method's practical potential. Results from DEDZ (Dalian Economic
      Development Zone) case show us the potential of emergy synthesis method at the
      industrial park level for environmental policy making. Its advantages and
      limitations are also discussed with avenues for future research identified.

PMID- 20805001
TI  - Proteomic analysis of serum of workers occupationally exposed to arsenic,
      cadmium, and lead for biomarker research: a preliminary study.
AB  - The main factor of environmental contamination is the presence of the heavy
      metals lead, cadmium, and arsenic. The aim of serum protein profile analysis of
      people chronically exposed to heavy metals is to find protein markers of early
      pathological changes. The study was conducted in a group of 389 healthy men
      working in copper foundry and 45 age-matched non-exposed healthy men.
      Toxicological test samples included whole blood, serum, and urine. Thirty-seven
      clinical parameters were measured. Based on the parameters values of the healthy
      volunteers, the centroid in 37-dimensional space was calculated. The individuals
      in the metal-exposed and control groups were ordered based on the Euclidean
      distance from the centroid defined by the first component according to Principal
      Component Analysis (PCA). Serum samples of two individuals, one from the control
      and one from the metal-exposed group, were chosen for proteomic analysis. In
      optimized conditions of two-dimensional gel electrophoresis (2-DE), two protein
      maps were obtained representing both groups. Twenty-eight corresponding protein
      spots from both protein maps were chosen and identified based on PDQuest analysis
      and the SWISS-2DPAGE database. From a panel of six proteins with differences in
      expression greater than a factor of two, three potential markers with the highest
      differences were selected: hemoglobin-spot 26 (pI 7.05, Mw 10.53), unidentified
      protein-spot 27 (pI 6.73, Mw 10.17), and unidentified protein-spot 25 (pI 5.75,
      Mw 12.07). Further studies are required to prove so far obtained results.
      Identified proteins could serve as potential markers of preclinical changes and
      could be in the future included in biomonitoring of people exposed to heavy
      metals.

PMID- 20805002
TI  - Reduced allele specific annexin A5 mRNA levels in placentas carrying the M2/ANXA5
      allele.
AB  - We aimed to trace the allele specific expression of ANXA5 mRNA in placentas
      carrying the M2 haplotype, conferring higher recurrent pregnancy loss risk, in
      order to verify directly the role of M2 in the relevant organ. The M2 allele in
      heterozygous placentas results in an average of 42% reduced ANXA5 mRNA levels as
      compared to the normal allele. Protein levels in these samples show considerable
      variations, impossible for statistical interpretation. The M2 allele of ANXA5 can
      be linked to reduced mRNA levels in heterozygous placentas and could result in
      more confined protein levels (lowered expression dynamics) of annexin A5.

PMID- 20805003
TI  - Regional differences in levels of chlorinated and brominated pollutants in
      mother's milk from primiparous women in Sweden.
AB  - Early life exposure to halogenated persistent organic pollutants, such as
      polychlorinated biphenyls (PCBs), the DDT metabolite p,p'
      dichlorodiphenyldichloroethane (p,p'-DDE), polybrominated diphenylethers (PBDEs),
      and hexabromocyclododecane (HBCD), may affect human health. We determined if
      there are regional differences in mother's milk levels of these compounds in
      Sweden. In year 2000-2004, milk was sampled from 204 randomly recruited
      primiparas from four regions of Sweden. Levels of the compounds were measured by
      gas chromatography with dual electron-capture detectors. Women were recruited at
      delivery in three hospitals located in urban areas in southern and central Sweden
      (Lund, Gothenburg and Uppsala), and in one hospital located in a more rural area
      in northern Sweden (Lycksele). Information about dietary habits and medical/life
      style factors were collected by questionnaires. Among PCB congeners, CB 153, CB
      138 and CB 180 showed the highest median concentrations (18-48 ng/g mother's milk
      lipid), whereas more than 50% of the women had CB 52, CB 101, CB 114, and CB 157
      levels below the LOQ (0.3-1.5 ng/g lipid). Median p,p'-DDE levels were in the
      range of 46-78 ng/g lipid. BDE 47 showed the highest median concentrations (1-2
      ng/g lipid) among the brominated compounds, whereas more than 50% of the women
      had levels of BDE 28, BDE 66, BDE 138, BDE 154, and HBCD below the LOQ (0.05-0.10
      ng/g lipid). Regional differences in median organohalogen compound concentrations
      were small, less than 2-fold. Lycksele women generally had the lowest levels of
      Sigmamono-and Sigmadi-ortho PCBs, mainly due to a lower average age. In contrast,
      these women had higher tetra- to penta-brominated PBDE levels, but no diet or
      life-style factor could explain this finding. Wide ranges of PBDEs and HBCD
      levels (up to 200-fold) were found, especially in the Lycksele area. The highest
      levels of PBDE were in the range of average levels found in mother's milk from
      North America, suggesting that food may not be the only source of exposure to
      PBDEs among some individuals.

PMID- 20805004
TI  - Antenatal anxiety disorder as a predictor of postnatal depression: a longitudinal
      study.
AB  - Previous research has implicated high levels of antenatal anxiety as a predictor
      of postnatal depression, but there is a paucity of evidence on the relationship
      between the various forms of anxiety and postnatal depression. A longitudinal
      study of 246 mothers (56 with antenatal generalised anxiety disorder (GAD), 68
      with antenatal generalised social phobia, 28 with both disorders in the antenatal
      period, and 94 with no antenatal GAD or social phobia) allowed us to explore
      whether antenatal social phobia and GAD predict high Edinburgh Postnatal
      Depression Scale (EPDS) scores (probable depression >12) at 10-14 days, 10-12
      weeks, 10 months, 14 months, and 24 months postnatally. We found that, after
      accounting for the presence of other antenatal anxiety disorders, antenatal
      depression, maternal age at child's birth, socio-economic status and ethnicity in
      the models, antenatal GAD independently predicted depression at all time points
      after delivery. A less robust relationship was found for antenatal social phobia,
      which predicted postnatal depression at only 10 months after birth. One
      possibility consistent with our findings is that there may be differences in the
      timing of postnatal depression with different forms of antenatal anxiety
      disorders.

PMID- 20805005
TI  - No clear potentiation of antidepressant medication effects by folic acid+vitamin
      B12 in a large community sample.
AB  - BACKGROUND: Observational studies link low folate levels to depressive symptoms
      and to poor antidepressant medication response. Evidence supports a role for
      folate in potentiating the effect of antidepressant medications. AIM: This
      prospective study examines the effects of folic acid+vitamin B12 supplementation
      and antidepressant medication in a community-based study of older adults with
      depressive symptoms. METHOD: A randomised controlled trial investigated the
      effectiveness of a medicinal and two behavioural preventive interventions over a
      two year period. The medicinal intervention compared dietary supplementation of
      400 mcg/d folic acid+100 mcg/d vitamin B12 to placebo. Self reported use of
      antidepressant medication over two years was recorded. Participants were screened
      for psychological distress using the Kessler Distress 10-Scale (K-10; >15
      eligible) and the main outcome measure was change in depressive symptoms on the
      Patient Health Questionnaire-9 (PHQ-9) at six weeks, six, 12 and 24 months. Nine
      hundred adults aged 60-74 years were included in the analysis, of whom 209
      (23.2%) reported antidepressant use during the follow-up period. RESULTS: A mixed
      model repeated measures analysis of variance for reduction in depressive symptoms
      found no significant three-way interaction between supplement group and
      antidepressant use over time on the PHQ-9 [F4, 825.1=0.32, p=0.87]. A small
      interaction between supplement group and antidepressant use over time was found
      for K-10 scores (F4, 799.5=2.50, p=0.0414). CONCLUSIONS: There was little
      evidence for the potentiation of antidepressant medication by folic acid+B12
      supplementation on depressive symptomatology. Further research should examine
      whether effects might be found at higher folic acid dosages or among clinical
      populations.

PMID- 20805006
TI  - Interleukin-18 deficiency reduces neuropeptide gene expressions in the mouse
      amygdala related with behavioral change.
AB  - In this study, we examined the effects of IL-18 deficiency on behaviors and gene
      expression profiles in 6 brain regions. IL-18(-/-) mice reduced depressive-like
      behavior and changed gene expressions predominantly in the amygdala compared with
      wild-type mice. Pathway analysis of the differentially expressed genes ranked
      behavior as the top-scored biological function. Of note, the absence of IL-18
      decreased Avp, Hcrt, Oxt, and Pmch mRNA levels and the number of arginine
      vasopressin- and oxytocin-positive cells in the amygdala, but not in the
      hypothalamus. Our results suggest that IL-18-dependent vasopressinergic and
      oxytocinergic circuitry in the amygdala may regulate depressive-like behaviors in
      mice.

PMID- 20805007
TI  - Effect of water activity on stress tolerance and biocontrol activity in
      antagonistic yeast Rhodosporidium paludigenum.
AB  - The aims of this study were to optimize the salt-adaptation conditions of the
      marine antagonistic yeast Rhodosporidium paludigenum and investigate the
      biocontrol activity of salt-induced cell suspensions of R. paludigenum on
      postharvest pathogens in fruits. Low water activity (a(w)=0.98, 0.97, 0.96, and
      0.95) inhibited the growth of R. paludigenum in nutrient yeast dextrose broth,
      but the yeast grew better in the medium modified with NaCl solute than other
      nonionic solutes. R. paludigenum grown in 6.6% NaCl-modified medium had higher
      viabilities (92.1%) at low water activity (a(w)=0.95) than control (81.1%) after
      48h incubation. The salt-adapted R. paludigenum also showed better viability than
      the un-adapted cells after being frozen, which may be related to the accumulation
      of intracellular trehalose. Moreover, the best biocontrol inhibition in pears and
      Chinese winter jujubes was obtained when R. paludigenum was grown in NaCl
      modified medium. Therefore, this study implies that improving physiological
      inducement methods may be a promising strategy for accelerating commercialization
      of biocontrol agents.

PMID- 20805008
TI  - Production of flavour-active methionol from methionine metabolism by yeasts in
      coconut cream.
AB  - Yeasts Candida kefyr NCYC143, Candida utilis CUM, Kluyveromyces lactis KL71,
      Saccharomyces bayanus SB1, Saccharomyces cerevisiae EC1118, Saccharomyces
      chevalieri CCICC1028, Candida famata (previously Torulopsis candida) CCICC1041
      and Williopsis saturnus var. saturnus CBS254 were screened for their ability to
      produce flavour-active methionol (3-methylthio-1-propanol) in coconut cream
      supplemented with l-methionine. The yeasts varied with their ability to produce
      methionol from methionine with Saccharomyces cerevisiae EC1118 producing the
      most, followed by Kluyveromyces lactis KL71. Little methionol was produced by the
      other yeasts. Methionol production by Kluyveromyces lactis KL71 was subjected to
      further studies under different conditions of initial pH (4.0-6.3), temperature
      (20-33  degrees C), l-methionine concentration (0.05-0.25%) and yeast extract
      concentration (0-0.50%); optimal conditions were established at pH 5.0, 33.0 
      degrees C, 0.15% l-methionine and 0.05% yeast extract. CharmAnalysisTM using SPME
      GC-MS was conducted on the coconut cream ferment; methional (3-methylthio-1
      propanal), methionol and 2-phenylethyl acetate were found to be the most potent
      aroma-active compounds. The product of coconut cream fermentation by
      Kluyveromyces lactis KL71 may be considered as a novel, plant-based, natural and
      complex flavoring bioingredient in food applications.

PMID- 20805009
TI  - Biofilm formation by Campylobacter jejuni in controlled mixed-microbial
      populations.
AB  - This study was to screen the ability of biofilm formation by Campylobacter jejuni
      strains found in New Zealand, and investigate the biofilm growth of C. jejuni in
      a controlled mixed-microbial population that includes five different bacteria.
      The ability of C. jejuni to form a biofilm in monoculture and mixed-microbial
      populations was measured in a laboratory assay using a microtiter plate screening
      assay. The optical density of the biofilm and cell growth from mixed-microbial
      populations was converted to a Biofilm Formation Index (BFI). This index was used
      to standardize the biofilm formation in the mixed-microbial populations. High BFI
      was observed for Enterococcus faecalis (2.30) and Staphylococcus simulans (3.75)
      when they were grown with C. jejuni multilocus sequence type ST-474: a dominant
      poultry and human-associated type in New Zealand. C. jejuni cells were recovered
      from most of the biofilms containing E. faecalis and/or S. simulans. These
      results suggest that E. faecalis and S. simulans may play a role in biofilm
      formation in the poultry environment as both of these microorganisms are found in
      poultry processing environments and were able to form a biofilm in association
      with C. jejuni under microaerobic conditions. Understanding the relationships
      among C. jejuni, E. faecalis and S. simulans in poultry processing plants and
      farms may help in the design of strategies to reduce the reservoir of
      contamination of these bacteria and reduce the incidence of campylobacteriosis.

PMID- 20805010
TI  - 4-Aminoquinoline derived antimalarials: synthesis, antiplasmodial activity and
      heme polymerization inhibition studies.
AB  - A new series of 4-aminoquinoline derivatives have been synthesized and found to
      be active against both susceptible and resistant strains of Plasmodium falciparum
      in vitro. Compound 1-[3-(7-chloro-quinolin-4-ylamino)-propyl]-3-cyclopropyl
      thiourea (7) exhibited superior in vitro activity against resistant strains of P.
      falciparum as compared to chloroquine (CQ). All the compounds showed resistance
      factor between 0.59 and 4.31 as against 5.05 for CQ. Spectroscopic studies
      suggested that this class of compounds act on heme polymerization target.

PMID- 20805011
TI  - Design, synthesis and in vitro evaluation of antitubercular and antimicrobial
      activity of some novel pyranopyrimidines.
AB  - The clinical significance of pyran and pyrimidine condensed systems and the raise
      in problem of multidrug resistant bacterial pathogens has directed us to
      synthesize pyranopyrimidine derivatives via the reactions of the versatile, 2
      amino-4-(4-methoxyphenyl)-4H-substituted chromene-3-carbonitrile with the
      appropriate reagents. The newly synthesized compounds were characterized by IR,
      (1)H NMR, (13)C NMR, Mass spectra and Elemental analysis. The compounds were
      evaluated for their in vitro antitubercular activity against Mycobacterium
      tuberculosis H(37)Rv [ATCC-27294] and antibacterial activity against
      Staphylococcus aureus [ATCC-25923] and Streptococcus pyogenes [MTCC-443] as gram
      positive, Escherichia coli [ATCC-25922] and Pseudomonas aeruginosa [MTCC-441] as
      gram-negative bacterial strains and antifungal activity against Aspergillus niger
      [MTCC-282]. Several derivatives exhibited pronounced antitubercular and
      antimicrobial activities.

PMID- 20805012
TI  - Design and synthesis of bioactive adamantanaminoalcohols and adamantanamines.
AB  - Adamantanamines 16, 18, 21, 24, 27, 28, 30, 32, 35, 36, 37, 40, 46 and 48 were
      synthesized and tested for anti-influenza A virus and trypanocidal activity. The
      stereoelectronic requirements for optimal antiviral and trypanocidal potency were
      investigated. The effect of introducing a hydroxyl group close to the amino group
      on this class of compounds was examined for the first time. Aminoalcohol 24
      proved to be the most active of the compounds tested against influenza A virus,
      being 6-fold more active than amantadine, equipotent to rimantadine and 26-fold
      more potent than ribavirin. Aminoalcohols 36 and 37 were found to have
      considerable activity against bloodstream forms of the African trypanosome,
      Trypanosoma brucei, being almost 10 times more potent than rimantadine.

PMID- 20805013
TI  - Poly propyl ether imine (PETIM) dendrimer: a novel non-toxic dendrimer for
      sustained drug delivery.
AB  - In the present study, an attempt was made to study the acute and sub-acute
      toxicity profile of G3-COOH Poly (propyl ether imine) [PETIM] dendrimer and its
      use as a carrier for sustained delivery of model drug ketoprofen. Drug-dendrimer
      complex was prepared and characterized by FTIR, solubility and in vitro drug
      release study. PETIM dendrimer was found to have significantly less toxicity in
      A541 cells compared to Poly amido amine (PAMAM) dendrimer. Further, acute and 28
      days sub-acute toxicity measurement in mice showed no mortality, hematological,
      biochemical or histopathological changes up to 80 mg/kg dose of PETIM dendrimer.
      The results of study demonstrated that G3-COOH PETIM dendrimer can be used as a
      safe and efficient vehicle for sustained drug delivery.

PMID- 20805014
TI  - Christmas and New Year as risk factors for death.
AB  - This paper poses three questions: (1) Does mortality from natural causes spike
      around Christmas and New Year? (2) If so, does this spike exist for all major
      disease groups or only specialized groups? (3) If twin holiday spikes exist, need
      this imply that Christmas and New Year are risk factors for death? To answer
      these questions, we used all official U.S. death certificates, 1979-2004 (n =
      57,451,944) in various hospital settings to examine daily mortality levels around
      Christmas and New Year. We measured the Christmas increase by comparing observed
      deaths with expected deaths in the week starting on Christmas. The New Year
      increase was measured similarly. The expected number of deaths was determined by
      locally weighted regression, given the null hypothesis that mortality is affected
      by seasons and trend but not by holidays. On Christmas and New Year, mortality
      from natural causes spikes in dead-on-arrival (DOA) and emergency department (ED)
      settings. There are more DOA/ED deaths on 12/25, 12/26, and 1/1 than on any other
      day. In contrast, deaths in non-DOA/ED settings display no holiday spikes. For
      DOA/ED settings, there are holiday spikes for each of the top five disease groups
      (circulatory diseases; neoplasms; respiratory diseases;
      endocrine/nutritional/metabolic diseases; digestive diseases). For all settings
      combined, there are holiday spikes for most major disease groups and for all
      demographic groups, except children. In the two weeks starting with Christmas,
      there is an excess of 42,325 deaths from natural causes above and beyond the
      normal winter increase. Christmas and New Year appear to be risk factors for
      deaths from many diseases. We tested nine possible explanations for these risk
      factors, but further research is needed.

PMID- 20805016
TI  - Validity of a brief screening instrument-CRAFFT in a multiethnic Asian
      population.
AB  - AIM: To validate the CRAFFT screening test, against the DSM IV Axis 1-based
      diagnostic inventory in a population of adolescents and young adult males in
      Singapore. METHODS: The 23,248 participants belonged to a cohort of males who had
      undergone a medical examination prior to enlistment for military service. This
      study took place between August 2004 and August 2005. Subjects underwent a two
      stage assessment and were administered the CRAFFT questionnaire and the Composite
      International Diagnostic Interview (CIDI). RESULTS: The mean age of the subjects
      was 19 years (range, 16 to 26 years). The CRAFFT showed moderately high levels of
      internal consistency (Cronbach's alpha=0.73). The optimum cutoff point for drug
      related disorder either abuse or dependence and alcohol-related disorder either
      abuse or dependence criterions were found at CRAFFT score of 1 or higher.
      CONCLUSION: The CRAFFT test is a valid means of screening adolescents for
      substance-related disorders in a multiethnic population of adolescent and young
      adult males.

PMID- 20805015
TI  - Phospholipase D-mTOR requirement for the Warburg effect in human cancer cells.
AB  - A characteristic of cancer cells is the generation of lactate from glucose in
      spite of adequate oxygen for oxidative phosphorylation. This property - known as
      the "Warburg effect" or aerobic glycolysis - contrasts with anaerobic glycolysis,
      which is triggered in hypoxic normal cells. The Warburg effect is thought to
      provide a means for cancer cells to survive under conditions where oxygen is
      limited and to generate metabolites necessary for cell growth. The shift from
      oxidative phosphorylation to glycolysis in response to hypoxia is mediated by the
      production of hypoxia-inducible factor (HIF) - a transcription factor family that
      stimulates the expression of proteins involved in glucose uptake and glycolysis.
      We reported previously that elevated phospholipase D (PLD) activity in renal and
      breast cancer cells is required for the expression of the alpha subunits of HIF1
      and HIF2. We report here that the aerobic glycolysis observed in human breast and
      renal cancer cells is dependent on the elevated PLD activity. Intriguingly, the
      effect of PLD on the Warburg phenotype was dependent on the mammalian target of
      rapamycin complex 1 (mTORC1) in the breast cancer cells and on mTORC2 in the
      renal cancer cells. These data indicate that elevated PLD-mTOR signaling, which
      is common in human cancer cells, is critical for the metabolic shift to aerobic
      glycolysis.

PMID- 20805017
TI  - Can parents prevent heavy episodic drinking by allowing teens to drink at home?
AB  - The current study examined whether permitting young women to drink alcohol at
      home during senior year of high school reduces the risk of heavy drinking in
      college. Participants were 449 college-bound female high school seniors,
      recruited at the end of their senior year. Participants were classified into one
      of three permissibility categories according to their baseline reports of whether
      their parents allowed them to drink at home: (a) not permitted to drink at all;
      (b) allowed to drink with family meals; (c) allowed to drink at home with
      friends. Repeated measures analysis of variance was used to compare the drinking
      behaviors of the three groups at the time of high school graduation and again
      after the first semester of college. Students who were allowed to drink at home
      during high school whether at meals or with friends, reported more frequent heavy
      episodic drinking (HED) in the first semester of college than those who reported
      not being allowed to drink at all. Those who were permitted to drink at home with
      friends reported the heaviest drinking at both time points. Path analysis
      revealed that the relationship between alcohol permissiveness and college HED was
      mediated via perceptions of parental alcohol approval.

PMID- 20805018
TI  - Light smoking in a predominantly Hispanic college student sample: a 7 day diary
      assessment.
AB  - Both Hispanic and college student populations smoke at non trivial rates but less
      frequently than other smoking groups. Limited information exists about the at
      risk times for smoking among those who smoke fewer than 10 cigarettes per day,
      particularly college students. Participants (n=116 young adults) completed a 7
      day Tobacco Consumption Diary by recording for each cigarette smoked: time and
      day, location, number of people present, number of smokers present, mood, and
      whether alcohol was consumed. Descriptive analyses suggest a variety of psycho
      social contexts within which light smoking may occur for a predominantly Hispanic
      sample of college students. Inferential analyses reveal a somewhat heterogeneous
      pattern of light smoking. Nevertheless, Thursday, Friday, and Saturday, as well
      as later hours of each day in particular are associated with an increased
      likelihood of smoking. Further study of intra-individual patterns of both
      Hispanic and college student light smoking is needed to identify the ideographic
      triggers that can be intervened upon to aid light smokers in cessation.

PMID- 20805019
TI  - Epilepsy in autism: A pathophysiological consideration.
AB  - Eighty cases of idiopathic autism with epilepsy and 97 cases without epilepsy
      were studied to evaluate the pathophysiology of epilepsy in autism. The initial
      visit to this clinic ranged 8months-30years 3months of age, and the current ages
      are 5years 8months-42years 3months, 60% reaching to over 30years of age. The
      average follow up duration is 22.2years+/-9.4years. The ages of onset of epilepsy
      were from 7months to 30years of age, with the two peaks at 3.2years and
      16.7years. EEG central focus appeared earlier than frontal focus. Abnormality of
      locomotion and atonic NREM were observed more frequently in epileptic group.
      These suggest the neuronal system related to abnormality of locomotion and atonic
      NREM, which are the hypofunction of the brainstem monoaminergic system, is the
      pathomechanism underling the epilepsy in autism. By showing the abnormal sleep
      wake rhythm and locomotion being the very initial symptoms in autism, we had
      shown the hypofunction of the brainstem monoaminergic system is the initial
      pathomechanism of autism. Thus, epilepsy in autism is not the secondary
      manifestation, but one of the pathognomonic symptoms of autism. The brainstem
      monoaminergic system project to the wider cortical area, and the initial
      monoaminergic hypofunction may lead to the central focus which appears earlier.
      The failure of the monoaminergic (serotonergic) system causes dysfunction of the
      pedunculo-pontine nucleus (PPN) and induces dysfunction of the dopamine (DA)
      system, and with development of the DA receptor supersensitivity consequently
      disinhibits the thalamo-frontal pathway, which after maturation of this pathway
      in teens cause the epileptogenesis in the frontal cortex.

PMID- 20805020
TI  - Regulatory T cell defect in APECED patients is associated with loss of naive
      FOXP3(+) precursors and impaired activated population.
AB  - The pathogenetic mechanisms of organ-specific autoimmune diseases remain obscured
      by the complexity of the genetic and environmental factors participating in the
      breakdown of tolerance. A unique opportunity to study the pathogenesis of human
      autoimmunity is provided by autoimmune polyendocrinopathy-candidiasis-ectodermal
      dystrophy (APECED), a rare inherited autoimmune disease caused by mutations in
      Autoimmune Regulator (AIRE) gene. Loss of AIRE function disrupts the deletion of
      autoreactive T cells and impairs the suppressive function of regulatory T (Treg)
      cells. Here we show by multiparameter flow cytometry that in healthy controls the
      peripheral naive Treg cell subset forms a slowly dividing, persistent reservoir
      of recent thymic emigrants (RTEs). In APECED patients the RTE Treg cells show
      accelerated turnover and shift to the activated pool and the RTE reservoir is
      depleted. Moreover, the activated Treg cell population in the patients expresses
      significantly less Forkhead box protein P3 (FOXP3) than in the healthy controls,
      consistent with the impairment of peripheral activation. Our results indicate
      that in addition to their thymic effects, loss-of-function mutations in AIRE
      disrupt the peripheral homeostasis and activation of Treg cells. This may
      synergize with failed negative selection to cause APECED.

PMID- 20805021
TI  - Homicide in discharged patients with schizophrenia and other psychoses: a
      national case-control study.
AB  - OBJECTIVE: To investigate factors associated with homicide after discharge from
      hospital in patients with schizophrenia and other psychoses. DESIGN: All
      homicides committed by patients with psychosis within 6 months of hospital
      discharge were identified in Sweden from 1988-2001 and compared with patients
      with psychoses discharged over the same time period who did not subsequently
      commit any violent offences. Medical records were then collected, and data
      extracted using a validated protocol. Interrater reliability tests were performed
      on a subsample, and variables with poor reliability excluded from subsequent
      analyses. RESULTS: We identified 47 cases who committed a homicide within 6
      months of discharge, and 105 controls who did not commit any violent offence
      after discharge. On univariate analyses, clinical factors on admission associated
      with homicide included evidence of poor self-care, substance misuse, and being
      previously hospitalized for a violent episode. Inpatient characteristics included
      having a severe mental illness for one year prior to admission. After-care
      factors associated with homicide were evidence of medication non-compliance and
      substance misuse. The predictive validity of combining two or three of these
      factors was not high. Depression appeared to be inversely associated with
      homicide, and there was no relationship with the presence of delusions or
      hallucinations. CONCLUSIONS: There are a number of potentially treatable factors
      that are associated with homicide in schizophrenia and other psychoses.
      Associations with substance misuse and treatment compliance could be the focus of
      therapeutic interventions if validated in other samples. However, their clinical
      utility in violence risk assessment remains uncertain.

PMID- 20805022
TI  - Evidence of specificity of a visual P3 amplitude modulation deficit in
      schizophrenia.
AB  - BACKGROUND: In a previous study, we found a reduced amplitude modulation of the
      visual P3 component of the event-related potential (ERP) in schizophrenic
      patients compared with healthy controls during inhibition in the Attention
      Network Test (ANT). The objective of the present study was to replicate this
      finding and to explore whether this cortical processing deficit is specific to
      schizophrenia. METHODS: Sixteen schizophrenic patients, sixteen depressive
      patients, and sixteen healthy controls matched for age, sex, and education were
      included. Participants were tested with the ANT, a test of selective attention
      that provides behavioral estimates for alerting, orienting, and inhibition. 32
      Channel electroencephalogram was recorded and visual P3 amplitudes were
      topographically analyzed and compared between groups. RESULTS: There were no
      significant behavioral between-group differences in terms of mean reaction time,
      accuracy, and ANT effects alerting, orienting, and inhibition. Absolute visual P3
      amplitude was not reduced in schizophrenia or depression. P3 amplitude modulation
      was defined as P3 amplitude at Pz as a function of ANT flanker conditions. We
      found a parietal P3 amplitude modulation deficit in schizophrenic patients (
      .015) that was absent in both healthy controls (-.705; p = .002) and depressive
      patients (-1.022; p = .001). CONCLUSION: The results provide evidence that a
      deficit of visual P3 amplitude modulation distinguishes schizophrenia from
      healthy and disease controls and provides greater discriminative power than
      absolute visual P3 amplitude.

PMID- 20805023
TI  - Drainage and bypass procedures for palliation of malignant diseases of the upper
      gastrointestinal tract.
AB  - Malignant diseases of the upper gastrointestinal tract are common and often
      diagnosed at a point when the opportunity for curative surgical resection has
      passed. Symptoms of luminal obstruction include nausea, vomiting, weight loss,
      pain, pruritus and jaundice. The median survival of patients who cannot be cured
      surgically is extremely short, with a duration of only a few months. Effective
      palliative techniques with a low morbidity and associated mortality are required.
      The length of hospital stay, rapid recovery and reduction in recurrent symptoms
      are important factors for patients and doctors to consider when planning
      treatment. Traditionally, surgical techniques were used, but in the last 20 years
      the availability of both endoscopic and interventional radiological procedures
      has increased. Furthermore, advances in technology such as the development of
      self-expanding metal stents and covered stent designs have provided more
      therapeutic options for the endoscopist and radiologist. Here we discuss the
      available treatments for the palliation of gastric outlet and biliary tract
      obstruction and the evidence for the respective approaches.

PMID- 20805025
TI  - Biochemical characterization of an intracellular 6G-fructofuranosidase from
      Xanthophyllomyces dendrorhous and its use in production of neo
      fructooligosaccharides (neo-FOSs).
AB  - An intracellular 6G-fructofuranosidase (endo-type enzyme) extracted from
      Xanthophyllomyces dendrorhous 269 efficiently hydrolyzes fructosyl-beta-(2->1)
      linked sucrose to produce neo-kestose as a main transglycosylation product. The
      enzyme with a molecular weight of 33 kDa was purified by DEAE-52 cellulose
      chromatography. Thirty-fivefold purification and a 13.4% enzyme activity recovery
      were achieved. Optimum enzyme activity occurred at pH 6.4 and 45  degrees C and
      the enzyme was stable at pH 4-7 and at 45  degrees C. Using sucrose as a
      substrate, the Km and Vmax values were, respectively, 511 mmol/l and 233
      MUmol/(min mg) for transfer activity and 62 mmol/l and 164 MUmol/(min mg) for
      hydrolytic activity. Under optimum conditions, a maximum concentration (73.9 g/l)
      of neo-fructooligosaccharides catalyzed by the endo-enzyme was obtained. These
      findings suggest that the purified endo-enzyme exhibits a high
      transfructosylation activity and it has potential for the industrial production
      of neo-FOSs.

PMID- 20805024
TI  - Cloning and expression in E. coli of an organic solvent-tolerant and alkali
      resistant glucose 1-dehydrogenase from Lysinibacillus sphaericus G10.
AB  - The gene gdh encoding an organic solvent-tolerant and alkaline-resistant NAD(P)
      dependent glucose 1-dehydrogenase (LsGDH) was cloned from Lysinibacillus
      sphaericus G10 and expressed in Escherichia coli. The recombinant LsGDH exhibited
      maximum activity at pH 9.5 and 50  degrees C. LsGDH displayed high stability at a
      wide pH ranging from 6.5 to 10.0 and was stable after incubation at 30  degrees C
      for 1 week in 25 mM sodium phosphate buffer (pH 6.5) in the absence or presence
      of NaCl. The activity of LsGDH was enhanced by Li+, Na+, K+, NH4+, Mg2+, and EDTA
      at pH 8.0. LsGDH exhibited high tolerance to 60% DMSO, 30% acetone, 30% methanol,
      30% ethanol, 10% n-propanol, 30% isopropanol, 60% n-hexanol and 30% n-hexane. The
      relationship between stability and chain length of the alcohols fit a Gaussian
      distribution model (R2>=0.94), and demonstrated lowest enzyme stability in C4
      alcohol. The results suggested that LsGDH was potentially useful for coenzyme
      regeneration in organic solvents or under alkaline conditions.

PMID- 20805026
TI  - A concise, total synthesis and antibacterial evaluation of 2-hydroxy-1-(1H-indol
      3-yl)-4-methylpentan-3-one.
AB  - Treatment of racemic 2-hydroxy-3-(1H-indol-3yl)propionic acid methyl ester (5)
      with isopropyl magnesium chloride provided the title compound 1 and its isomer, 3
      hydroxy-1-(indol-3-yl)-4-methylpentan-2-one (9). Both enantiomers (>96% ee) of
      each component were obtained via semi-preparative chiral supercritical fluid
      chromatography (SFC). In contrast to previous reports, these compounds, as well
      as their acetate derivatives, were not active or very weakly active against 16
      bacterial strains, including Escherichia coli, Bacillus subtilis and
      Staphylococcus aureus.

PMID- 20805027
TI  - Design, synthesis and in vitro evaluation of (R)-4-(2-(tert-butylamino)-1
      hydroxyethyl)-2-(hydroxymethyl)phenyl hydrogen phenylboronate: a novel salbutamol
      derivative with high intrinsic efficacy on the beta2 adrenoceptor.
AB  - We tested a set of boron containing arylethanolamine derivatives on the human and
      guinea pig beta(2) adrenoceptor (beta(2)AR) 3-D structures by docking
      methodology. The compound with the highest affinity based on docking analysis,
      (R)-4-(2-(tert-butylamino)-1-hydroxyethyl)-2-(hydroxymethyl)phenyl hydrogen
      phenylboronate (boronterol) was synthesized, characterized and tested in guinea
      pig tracheal rings at basal tone and with histamine-induced contractions.
      Boronterol was at least eightfold more potent than salbutamol as a smooth muscle
      relaxant drug (judged by the EC(50) values) and showed a similar maximal relaxant
      effect as isoproterenol. ICI118,551 showed competitive antagonism on the relaxing
      effect of boronterol. These results suggest the beta(2)AR agonist action of
      boronterol.

PMID- 20805028
TI  - 6,7-Dihydroxy-4-phenylcoumarin as inhibitor of aldose reductase 2.
AB  - We report the structure-activity relationship of a series of coumarins as aldose
      reductase 2 (ALR2) inhibitors and their suppressive effect on the accumulation of
      galactitol in the rat lens. We evaluated their ALR2 selectivity profile against
      sorbitol dehydrogenase and aldehyde reductase (ALR1). Our study revealed that
      substitutions in the C7 OH group enhanced the potency toward ALR2, while the C6
      OH group interferes with ALR1 inhibition activity. Having the phenyl moiety at C4
      leads to improved potency and improved selectivity. A molecular docking study
      suggested that 6,7-dihydroxy-4-phenylcoumarin (15) binds to ALR2 in a different
      manner from epalrestat. Furthermore, compound 15 clearly suppressed galactitol
      accumulation in a dose-dependent manner. These results provide an insight into
      the structural requirements of coumarins for developing a new-type of selective
      ALR2 inhibitor.

PMID- 20805029
TI  - 2,3-Disubstituted acrylamides as potent glucokinase activators.
AB  - The phenylacetamide 1 represents the archtypical glucokinase activator (GKA) in
      which only the R-isomer is active. In order to probe whether the chiral center
      could be replaced, we prepared a series of olefins 2 and show in the present work
      that these compounds represent a new class of GKAs. Surprisingly, the SAR of the
      new series paralleled that of the saturated derivatives with the exception that
      there was greater tolerance for larger alkyl and cycloalkyl groups at R(2) region
      in comparison to the phenylacetamides. In normal Wistar rats, the 2,3
      disubstituted acrylamide analog 10 was well absorbed and demonstrated robust
      glucose lowering effects.

PMID- 20805030
TI  - Condensed E. coli cultures for highly efficient production of proteins containing
      unnatural amino acids.
AB  - Current biosynthetic methods for producing proteins containing site-specifically
      incorporated unnatural amino acids are inefficient because the majority of the
      amino acid goes unused. Here we present a universal approach to improve the
      efficiency of such processes using condensed Escherichia coli cultures.

PMID- 20805031
TI  - A novel series of positive modulators of the AMPA receptor: discovery and
      structure based hit-to-lead studies.
AB  - Starting from an HTS derived hit 1, application of biostructural data facilitated
      rapid optimization to lead 22, a novel AMPA receptor modulator. This is the first
      demonstration of how structure based drug design can be exploited in an
      optimization program for a glutamate receptor.

PMID- 20805032
TI  - Retinobenzaldehydes as proper-trafficking inducers of folding-defective P23H
      rhodopsin mutant responsible for retinitis pigmentosa.
AB  - The Retinitis pigmentosa (RP)-causing mutant of rhodopsin, P23H rhodopsin, is
      folding-defective and unable to traffic beyond the endoplasmic reticulum (ER).
      This ER retention, and in some cases aggregation, are proposed to result in ER
      stress and eventually cell death. The endogenous rhodopsin ligand 11-cis-retinal
      and its isomer 9-cis-retinal have been shown to act as pharmacological
      chaperones, promoting proper folding and trafficking of the P23H rhodopsin. In
      spite of this promising effect, the development of retinals and related
      polyenealdehydes as pharmacological agents has been hampered by their undesirable
      properties, which include chemical instability, photolability, and potential
      retinoidal actions. Here, we report the design and synthesis of a class of more
      stable nonpolyene-type rhodopsin ligands, structurally distinct from, and with
      lower toxicity than, retinals. A structure-activity relationship study was
      conducted using cell-surface expression assay to quantify folding/trafficking
      efficiency of P23H rhodopsin.

PMID- 20805033
TI  - Identification of organoselenium compounds that possess chemopreventive
      properties in human prostate cancer LNCaP cells.
AB  - The process of cancer development consists of three sequential stages termed
      initiation, promotion, and progression. Oxidative stress damages DNA and
      introduces mutations into oncogenes or tumor suppressor genes, thus contributing
      to cancer development. Cancer chemoprevention is defined to prevent or delay the
      development of cancer by the use of natural or synthetic substances. In the
      present study, we synthesized a series of organoselenium compounds and evaluated
      their possible chemopreventive properties in human prostate cancer LNCaP cells.
      Among 42 organoselenium compounds tested, two compounds, 3-selena-1-dethiacephem
      13 and 3-selena-1-dethiacephem 14 strongly activated the Nrf2/ARE (antioxidant
      response element) signaling and thus markedly increased expression of heme
      oxygenase-1 (HO-1), a phase II antioxidant enzyme. Translocation of Nrf2 to the
      nucleus preceded HO-1 protein induction by two compounds. The intracellular ROS
      level was strongly reduced immediately after treatment with these compounds,
      showing that they are potent antioxidants. Finally, both compounds inhibited cell
      growth via cell cycle arrest. Our findings suggest that compounds 13 and 14 could
      not only attenuate oxidative stress through Nrf2/ARE activation and direct ROS
      scavenging but also inhibit cell growth. Thus, these compounds possess the
      potential as pharmacological agents for chemoprevention of human prostate cancer.

PMID- 20805034
TI  - Comparative nuclease and anti-cancer properties of the naturally occurring
      malabaricones.
AB  - The nuclease activities of the malabaricones have been studied so as to establish
      a structure-activity correlation and deduce the mechanistic pathway of the
      process. The inactivity of malabaricone A and malabaricone D revealed that the
      resorcinol moiety, present in the malabaricones did not contribute to the
      nuclease activity. Amongst the test compounds, malabaricone C (mal C) containing
      a B-ring catechol moiety showed significantly better Cu(II)-dependent nuclease
      activity than the partially methylated catechol derivative, mal B and curcumin.
      Mal C was found to bind efficiently with Cu(II) and DNA to facilitate the DNA
      nicking via a site-specifically generated Cu(I)-peroxo complex. Consistent with
      its Cu(II)-dependent nuclease property, mal C showed better cytotoxicity
      (IC(50)=5.26+/-1.20 MUM) than curcumin (IC(50)=24.46+/-3.32 MUM) against the MCF
      7 human breast cancer cell line. The mal C-induced killing of the MCF-7 cells
      followed an apoptotic pathway involving oxidative damage to the cellular DNA.

PMID- 20805035
TI  - Enhanced potency of individual and bivalent DNA replicon vaccines or conventional
      DNA vaccines by formulation with aluminum phosphate.
AB  - DNA vaccines against botulinum neurotoxin (BoNTs) induce protective humoral
      immune responses in mouse model, but when compared with conventional vaccines
      such as toxoid and protein vaccines, DNA vaccines often induce lower antibody
      level and protective efficacy and are still necessary to increase their potency.
      In this study we evaluated the potency of aluminum phosphate as an adjuvant of
      DNA vaccines to enhance antibody responses and protective efficacy against
      botulinum neurotoxin serotypes A and B in Balb/c mice. The administration of
      these individual and bivalent plasmid DNA replicon vaccines against botulinum
      neurotoxin serotypes A and B in the presence of aluminum phosphate improved both
      antibody responses and protective efficacy. Furthermore, formulation of
      conventional plasmid DNA vaccines encoding the same Hc domains of botulinum
      neurotoxin serotypes A and B with aluminum phosphate adjuvant increased both
      antibody responses and protective efficacy. These results indicate aluminum
      phosphate is an effective adjuvant for these two types of DNA vaccines (i.e.,
      plasmid DNA replicon vaccines and conventional plasmid DNA vaccines), and the
      vaccine formulation described here may be an excellent candidate for further
      vaccine development against botulinum neurotoxins.

PMID- 20805036
TI  - EPR distance measurements in deuterated proteins.
AB  - One of the major problems facing distance determination by pulsed EPR, on spin
      labeled proteins, has been the short relaxation time T(m). Solvent deuteration
      has previously been used to slow relaxation and so extend the range of distance
      measurement and sensitivity. We demonstrate here that deuteration of the
      underlying protein, as well as the solvent, extends the T(m) to a considerable
      degree. Longer T(m) gives greatly enhanced sensitivity, much extended distance
      measurement, more reliable distance distribution calculation and better baseline
      correction.

PMID- 20805037
TI  - Sonochemical fabrication of 8-hydroxyquinoline aluminum (Alq3) nanoflowers with
      high electrogenerated chemiluminescence.
AB  - Well-defined Alq(3) nanoflowers were fabricated via a facile and fast
      sonochemical route. X-ray diffraction (XRD), X-ray photoelectron spectroscopy
      (XPS), field-emission scanning electron microscopy (SEM) and transmission
      electron microscopy (TEM) were used to characterize the structure and shape of
      the as-prepared product. The results showed that the resulting Alq(3) was
      composed of nanobelts with thickness about 50 nm, average widths of 200 nm, and
      length up to 10 MUm. The Alq(3) nanoflowers exhibited good electrogenerated
      chemiluminescence behavior.

PMID- 20805038
TI  - Cu(OAc)2/MCM-41: an efficient and solid acid catalyst for synthesis of 2
      arylbenzothiazoles under ultrasound irradiation.
AB  - A new, convenient method for the syntheses of 2-arylbenzothiazoles is described
      in the presence of catalytic amounts of Cu(OAc)(2)/MCM-41 under ultrasonic
      irradiation. Short reaction times, easy and quick isolation of the products,
      reusability of the catalyst and excellent yields are the main advantages of this
      procedure.

PMID- 20805040
TI  - CD23-mediated cell signaling in human B cells differs from signaling in cells of
      the monocytic lineage.
AB  - CD23 is the low affinity receptor for IgE and in B cells CD23 has been proposed
      to play a role in the regulation of IgE synthesis. CD23 is expressed also on
      other cell types including monocytes/macrophages, eosinophils, follicular
      dendritic cells and intestinal epithelial cells none of which is capable of
      expressing IgE. The diverse nature of the expressing cells suggests that either
      the CD23-mediated signal transduction pathway may be different among the cell
      types or biological outcomes differ in different cells in response to the same
      signaling pathway. To address this issue, the CD23 signaling pathway was analyzed
      and compared in primary tonsillar B cells and in the monocytic cell lines U937
      and THP-1. Activation of the tyrosine kinase Fyn and the serine/threonine kinase
      Akt were only observed in B cells. These results suggest that the CD23-mediated
      signal transduction pathways in human B cells and human monocytes are different.

PMID- 20805039
TI  - Possible role of LECT2 as an intrinsic regulatory factor in SEA-induced toxicity
      in d-galactosamine-sensitized mice.
AB  - To elucidate whether leukocyte cell-derived chemotaxin 2 (LECT2) controls the
      progression of staphylococcal enterotoxin A (SEA)-induced toxicity, we examined
      the role of LECT2 in a mouse model. Almost all the C57BL/6J (B6) mice survived
      for 72 h after the injection of 0.1 MUg of SEA and 20 mg of d-galactosamine (d
      GalN). However, the same treatment protocol in LECT2(-/-) mice produced a high
      lethality (~90%), severe hepatic apoptosis, and massive hepatic and pulmonary
      hemorrhage, similar to the situation observed in B6 mice treated with 1.0 MUg
      SEA/d-GalN. The plasma LECT2 levels in B6 mice treated with 1.0 MUg SEA/d-GalN
      were inversely correlated with the plasma cytokine levels and were associated
      with prognosis. LECT2 administration increased the survival of B6 mice and down
      regulated TNF-alpha and IL-6. These results suggest the involvement of LECT2 in
      the regulation of fatal SEA-induced toxicity in d-GalN-sensitized mice.

PMID- 20805041
TI  - Increased Tim-3 expression on peripheral lymphocytes from patients with
      rheumatoid arthritis negatively correlates with disease activity.
AB  - Tim-3 has been reported as an important regulatory molecule and plays a pivotal
      role in several autoimmunity diseases. Here, we demonstrated the increased
      expression of Tim-3 on peripheral CD4(+) T, CD8(+) T, NKT cells and monocytes
      from RA patients compared to those from healthy controls. Percentage of Tim-3(+)
      cells in peripheral blood mononuclear cells (PBMCs) showed an inverse correlation
      with disease activity score 28 (DAS28) and plasma TNF-alpha level. Similar
      negative correlations were found between disease activity and Tim-3 levels on
      CD4(+) T, CD8(+) T and NKT cells. Consistently, Tim-3 expression on CD3(+) T
      cells was further increased in patients with disease remission after treatment.
      Tim-3 expression on CD8(+) T and NKT cells negatively correlates with plasma TNF
      alpha. Our results suggest that Tim-3 might participate in the proceeding of RA
      by its negative regulation on various T cell subsets. Tim-3 might be a potential
      new marker for assessing severity of RA.

PMID- 20805042
TI  - Analgesia requirements in patients undergoing DIEP flap breast reconstructions:
      rib preservation versus rib sacrifice.

PMID- 20805045
TI  - Modeling gross damage in tile-based nanomanufacturing by DNA self-assembly.
AB  - This paper proposes a novel model for gross damage as occurring in tile-based
      nanomanufacturing by DNA self-assembly. Gross damage occurs due to exogenous
      agents (such as radiation and tip-sample interactions) and is modeled as a hole
      (with a large number of empty tile sites) in the aggregate of the self-assembly.
      A stochastic analysis based on Markov chains for the tile binding process is
      pursued for regrowth of the tiles. This analysis establishes resilience as the
      probability to regrow the target pattern in the area affected by the gross
      damage. The conditions by which regrowth of a hole is favorable (i.e., at high
      resilience) compared with normal growth are established by considering
      temperature of aggregation and bond energy. As examples, two patterns for nano
      interconnects are analyzed based on the proposed model.

PMID- 20805043
TI  - Filtered multitensor tractography.
AB  - We describe a technique that uses tractography to drive the local fiber model
      estimation. Existing techniques use independent estimation at each voxel so there
      is no running knowledge of confidence in the estimated model fit. We formulate
      fiber tracking as recursive estimation: at each step of tracing the fiber, the
      current estimate is guided by those previous. To do this we perform tractography
      within a filter framework and use a discrete mixture of Gaussian tensors to model
      the signal. Starting from a seed point, each fiber is traced to its termination
      using an unscented Kalman filter to simultaneously fit the local model to the
      signal and propagate in the most consistent direction. Despite the presence of
      noise and uncertainty, this provides a causal estimate of the local structure at
      each point along the fiber. Using two- and three-fiber models we demonstrate in
      synthetic experiments that this approach significantly improves the angular
      resolution at crossings and branchings. In vivo experiments confirm the ability
      to trace through regions known to contain such crossing and branching while
      providing inherent path regularization.

PMID- 20805046
TI  - Influence of uncertain electrical properties on the conditions for the onset of
      electroporation in an eukaryotic cell.
AB  - A detailed numerical investigation concerning the influence on the electrical
      response of an eukaryotic cell model due to the variations of the conductivity
      and permittivity of the plasma and nuclear membranes is carried out by means of a
      vertex analysis. The dynamics of three cell performances, the voltages across the
      external and the nuclear membrane, and the pores density are analyzed by adopting
      a novel FEM-based model coupled with the nonlinear equation describing the
      electroporation (EP) phenomenon. The variations of the electrical and
      morphological performances, when the cell is stressed by a nonideal step input,
      are studied in three interesting regimes, i.e., at the nominal threshold for the
      onset of EP, and when the applied stress is over or under the EP threshold. The
      performed numerical analysis puts in evidence that, around the nominal EP
      threshold, uncertainties may lead to an indeterminate state of the plasma
      membrane, whereas the other two regimes remain well definite.

PMID- 20805047
TI  - Volitional control of a prosthetic knee using surface electromyography.
AB  - This paper presents a method for providing volitional control of a powered knee
      prosthesis during nonweight-bearing activity such as sitting. The method utilizes
      an impedance framework, such that the joint can be programmed with a given
      stiffness and damping that reflects the nominal impedance properties of an intact
      joint. Volitional movement of the knee joint is commanded via the stiffness set
      point angle of the joint impedance, which is commanded by the user as a function
      of the measured surface electromyogram (EMG) from the hamstring and quadriceps
      muscles of the residual limb. Rather than using the respective EMG measurements
      from these muscles to directly command the flexion or extension set point of the
      knee, the presented approach utilizes a combination of quadratic discriminant
      analysis and principal component analysis to align the user's intent to flex or
      extend the knee joint with the pattern of measured EMG. The approach was
      implemented on three transfemoral amputees, and their ability to control knee
      movement was characterized by a set of knee joint trajectory tracking tasks. Each
      amputee subject also performed the same set of trajectory tracking tasks with his
      sound side (intact) knee joint. The average root mean square trajectory tracking
      errors of the prosthetic knee employing the EMG-based volitional control and the
      intact knee of the three subjects were 6.2 degrees  and 5.2 degrees ,
      respectively.

PMID- 20805048
TI  - A brain-deformation framework based on a linear elastic model and evaluation
      using clinical data.
AB  - In image-guided neurosurgery, brain tissue displacement and deformation during
      neurosurgical procedures are a major source of error. In this paper, we implement
      and evaluate a linear-elastic-model-based framework for correction of brain shift
      using clinical data from five brain tumor patients. The framework uses a linear
      elastic model to simulate brain-shift behavior. The model is driven by cortical
      surface deformations, which are tracked using a surface-tracking algorithm
      combined with a laser-range scanner. The framework performance was evaluated
      using displacements of anatomical landmarks, tumor contours and self-defined
      evaluation parameters. The results show that tumor deformations predicted by the
      present framework agreed well with the ones observed intraoperatively, especially
      in the parts of the larger deformations. On average, a brain shift of 3.9 mm and
      a tumor margin shift of 4.2 mm were corrected to 1.2 and 1.3 mm, respectively.
      The entire correction process was performed in less than 5 min. The data from
      this study suggest that the technique is a suitable candidate for intraoperative
      brain-deformation correction.

PMID- 20805049
TI  - A self-powered telemetry system to estimate the postoperative instability of a
      knee implant.
AB  - Estimating in vivo the life span of a total knee replacement prosthesis is
      currently done by estimating the polyethylene (PE) wear rate from measurement of
      the femorotibial distance using X-ray photographies. This efficient method
      requires, however, waiting for few years to obtain a readout. This letter
      proposes using another metric that can be obtained within a couple of months of
      surgery, namely the center of pressure (COP). This metric represents the point,
      where the axial force applies the most onto the tibial tray. The displacement of
      the COP with respect to its ideal position can be used to estimate the wear and
      the life span of the PE. This requires the implant to be fitted with a telemetry
      system described briefly. The proposed method is supported by measures and
      simulations.

PMID- 20805050
TI  - Adaptive lag synchronization for competitive neural networks with mixed delays
      and uncertain hybrid perturbations.
AB  - This paper investigates the problem of adaptive lag synchronization for a kind of
      competitive neural network with discrete and distributed delays (mixed delays),
      as well as uncertain nonlinear external and stochastic perturbations (hybrid
      perturbations). A simple but robust adaptive controller is designed such that the
      response system can lag-synchronize with a drive system. Based on the Lyapunov
      stability theory and some suitable Lyapunov-Krasovskii functionals, several
      sufficient conditions ensuring the lag synchronization are developed. Our
      synchronization criteria are easily verified and do not need to solve any linear
      matrix inequality. Some existing results are improved and extended. Moreover, the
      designed adaptive controller has better anti-interference capacity and is more
      practical than the usual adaptive controller. Numerical simulations are exploited
      to show the effectiveness of the theoretical results.

PMID- 20805051
TI  - RAMOBoost: Ranked Minority Oversampling in Boosting.
AB  - In recent years, learning from imbalanced data has attracted growing attention
      from both academia and industry due to the explosive growth of applications that
      use and produce imbalanced data. However, because of the complex characteristics
      of imbalanced data, many real-world solutions struggle to provide robust
      efficiency in learning-based applications. In an effort to address this problem,
      this paper presents Ranked Minority Oversampling in Boosting (RAMOBoost), which
      is a RAMO technique based on the idea of adaptive synthetic data generation in an
      ensemble learning system. Briefly, RAMOBoost adaptively ranks minority class
      instances at each learning iteration according to a sampling probability
      distribution that is based on the underlying data distribution, and can
      adaptively shift the decision boundary toward difficult-to-learn minority and
      majority class instances by using a hypothesis assessment procedure. Simulation
      analysis on 19 real-world datasets assessed over various metrics-including
      overall accuracy, precision, recall, F-measure, G-mean, and receiver operation
      characteristic analysis-is used to illustrate the effectiveness of this method.

PMID- 20805052
TI  - Human tracking using convolutional neural networks.
AB  - In this paper, we treat tracking as a learning problem of estimating the location
      and the scale of an object given its previous location, scale, as well as current
      and previous image frames. Given a set of examples, we train convolutional neural
      networks (CNNs) to perform the above estimation task. Different from other
      learning methods, the CNNs learn both spatial and temporal features jointly from
      image pairs of two adjacent frames. We introduce multiple path ways in CNN to
      better fuse local and global information. A creative shift-variant CNN
      architecture is designed so as to alleviate the drift problem when the
      distracting objects are similar to the target in cluttered environment.
      Furthermore, we employ CNNs to estimate the scale through the accurate
      localization of some key points. These techniques are object-independent so that
      the proposed method can be applied to track other types of object. The capability
      of the tracker of handling complex situations is demonstrated in many testing
      sequences.

PMID- 20805053
TI  - Multiclass relevance vector machines: sparsity and accuracy.
AB  - In this paper, we investigate the sparsity and recognition capabilities of two
      approximate Bayesian classification algorithms, the multiclass multi-kernel
      relevance vector machines (mRVMs) that have been recently proposed. We provide an
      insight into the behavior of the mRVM models by performing a wide experimentation
      on a large range of real-world datasets. Furthermore, we monitor various model
      fitting characteristics that identify the predictive nature of the proposed
      methods and compare against existing classification techniques. By introducing
      novel convergence measures, sample selection strategies and model improvements,
      it is demonstrated that mRVMs can produce state-of-the-art results on multiclass
      discrimination problems. In addition, this is achieved by utilizing only a very
      small fraction of the available observation data.

PMID- 20805054
TI  - Clustered Nystrom method for large scale manifold learning and dimension
      reduction.
AB  - Kernel (or similarity) matrix plays a key role in many machine learning
      algorithms such as kernel methods, manifold learning, and dimension reduction.
      However, the cost of storing and manipulating the complete kernel matrix makes it
      infeasible for large problems. The Nystrom method is a popular sampling-based low
      rank approximation scheme for reducing the computational burdens in handling
      large kernel matrices. In this paper, we analyze how the approximating quality of
      the Nystrom method depends on the choice of landmark points, and in particular
      the encoding powers of the landmark points in summarizing the data. Our (non
      probabilistic) error analysis justifies a "clustered Nystrom method" that uses
      the k-means clustering centers as landmark points. Our algorithm can be applied
      to scale up a wide variety of algorithms that depend on the eigenvalue
      decomposition of kernel matrix (or its variant), such as kernel principal
      component analysis, Laplacian eigenmap, spectral clustering, as well as those
      involving kernel matrix inverse such as least-squares support vector machine and
      Gaussian process regression. Extensive experiments demonstrate the competitive
      performance of our algorithm in both accuracy and efficiency.

PMID- 20805055
TI  - On linear combinations of dichotomizers for maximizing the area under the ROC
      curve.
AB  - In this paper, we propose a method for the linear combination of several
      dichotomizers aimed at maximizing the area under the receiver operating
      characteristic (ROC) curve of the resulting classification system. This is
      particularly suited for real applications where it is difficult to exactly
      determine the key parameters such as costs and priors. In such cases, the
      accuracy is not adequate in measuring the quality of a classification system,
      while the ROC analysis provides the right tools for an appropriate assessment of
      the classification performance. The proposed approach revealed to be particularly
      effective with respect to other widespread combination rules both on artificial
      and real applications.

PMID- 20805056
TI  - Barometric pressure and triaxial accelerometry-based falls event detection.
AB  - Falls and fall related injuries are a significant cause of morbidity, disability,
      and health care utilization, particularly among the age group of 65 years and
      over. The ability to detect falls events in an unsupervised manner would lead to
      improved prognoses for falls victims. Several wearable accelerometry and
      gyroscope-based falls detection devices have been described in the literature;
      however, they all suffer from unacceptable false positive rates. This paper
      investigates the augmentation of such systems with a barometric pressure sensor,
      as a surrogate measure of altitude, to assist in discriminating real fall events
      from normal activities of daily living. The acceleration and air pressure data
      are recorded using a wearable device attached to the subject's waist and analyzed
      offline. The study incorporates several protocols including simulated falls onto
      a mattress and simulated activities of daily living, in a cohort of 20 young
      healthy volunteers (12 male and 8 female; age: 23.7 +/-3.0 years). A
      heuristically trained decision tree classifier is used to label suspected falls.
      The proposed system demonstrated considerable improvements in comparison to an
      existing accelerometry-based technique; showing an accuracy, sensitivity and
      specificity of 96.9%, 97.5%, and 96.5%, respectively, in the indoor environment,
      with no false positives generated during extended testing during activities of
      daily living. This is compared to 85.3%, 75%, and 91.5% for the same measures,
      respectively, when using accelerometry alone. The increased specificity of this
      system may enhance the usage of falls detectors among the elderly population.

PMID- 20805057
TI  - Robust neuro-sliding mode multivariable control strategy for powered wheelchairs.
AB  - This paper proposes an advanced robust multivariable control strategy for a
      powered wheelchair system. The new control strategy is based on a combination of
      the systematic triangularization technique and the robust neuro-sliding mode
      control approach. This strategy effectively copes with parameter uncertainties
      and external disturbances in real-time in order to achieve robustness and optimal
      performance of a multivariable system. This novel strategy reduces coupling
      effects on a multivariable system, eliminates chattering phenomena, and avoids
      the plant Jacobian calculation problem. Furthermore, the strategy can also
      achieve fast and global convergence using less computation. The effectiveness of
      the new multivariable control strategy is verified in real-time implementation on
      a powered wheelchair system. The obtained results confirm that robustness and
      desired performance of the overall system are guaranteed, even under parameter
      uncertainty and external disturbance effects.

PMID- 20805058
TI  - Design and implementation of a P300-based brain-computer interface for
      controlling an internet browser.
AB  - An electroencephalographic (EEG) brain-computer interface (BCI) internet browser
      was designed and evaluated with 10 healthy volunteers and three individuals with
      advanced amyotrophic lateral sclerosis (ALS), all of whom were given tasks to
      execute on the internet using the browser. Participants with ALS achieved an
      average accuracy of 73% and a subsequent information transfer rate (ITR) of 8.6
      bits/min and healthy participants with no prior BCI experience over 90% accuracy
      and an ITR of 14.4 bits/min. We define additional criteria for unrestricted
      internet access for evaluation of the presented and future internet browsers, and
      we provide a review of the existing browsers in the literature. The P300-based
      browser provides unrestricted access and enables free web surfing for individuals
      with paralysis.

PMID- 20805059
TI  - A training system of orientation and mobility for blind people using acoustic
      virtual reality.
AB  - A new auditory orientation training system was developed for blind people using
      acoustic virtual reality (VR) based on a head-related transfer function (HRTF)
      simulation. The present training system can reproduce a virtual training
      environment for orientation and mobility (O&M) instruction, and the trainee can
      walk through the virtual training environment safely by listening to sounds such
      as vehicles, stores, ambient noise, etc., three-dimensionally through headphones.
      The system can reproduce not only sound sources but also sound reflection and
      insulation, so that the trainee can learn both sound location and obstacle
      perception skills. The virtual training environment is described in extensible
      markup language (XML), and the O&M instructor can edit it easily according to the
      training curriculum. Evaluation experiments were conducted to test the efficiency
      of some features of the system. Thirty subjects who had not acquired O&M skills
      attended the experiments. The subjects were separated into three groups: a no
      training group, a virtual-training group using the present system, and a real
      training group in real environments. The results suggested that virtual-training
      can reduce "veering" more than real-training and also can reduce stress as much
      as real training. The subjective technical and anxiety scores also improved.

PMID- 20805062
TI  - Challenging clinical scenarios: treatment of patients with triple-negative or
      basal-like metastatic breast cancer.
AB  - There is now compelling evidence to suggest that the biologic features of breast
      tumors affect response to specific therapies. Triple-negative breast cancer
      (TNBC) refers to a heterogeneous group of tumors that do not express the
      estrogen, progesterone, or HER2/neu receptors. By gene expression analysis, most
      (but not all) TNBCs are categorized as basal-like. TNBCs are often associated
      with particularly poor outcomes, with early development of chemotherapy
      resistance. There have been significant improvements in the outcome of other
      subtypes of breast cancer, including hormone receptor-positive/HER2+ tumors,
      attributed to the addition of targeted therapy, including hormonal agents and
      trastuzumab. However, no specific targeted agents are currently available for the
      treatment of TNBC. This review aims to collate and describe the most recent data
      on both cytotoxic and targeted therapies that have demonstrated efficacy in the
      management of metastatic TNBC. Evidence of response to various agents in early
      stage breast cancer will be included, where relevant. Targeted agents that have
      been investigated in the treatment of TNBC include inhibitors of poly(ADP-ribose)
      polymerase, angiogenesis, mammalian target of rapamycin, epidermal growth factor
      receptor, and Src. Several of these agents have shown considerable promise.

PMID- 20805060
TI  - Long isoforms of NRF1 contribute to arsenic-induced antioxidant response in human
      keratinocytes.
AB  - BACKGROUND: Human exposure to inorganic arsenic (iAs), a potent oxidative
      stressor, causes various dermal disorders, including hyperkeratosis and skin
      cancer. Nuclear factor-erythroid 2-related factor 1 (NRF1, also called NFE2L1)
      plays a critical role in regulating the expression of many antioxidant response
      element (ARE)-dependent genes. OBJECTIVES: We investigated the role of NRF1 in
      arsenic-induced antioxidant response and cytotoxicity in human keratinocytes.
      RESULTS: In cultured human keratinocyte HaCaT cells, inorganic arsenite (iAs3+)
      enhanced the protein accumulation of long isoforms (120-140 kDa) of NRF1 in a
      dose- and time-dependent fashion. These isoforms accumulated mainly in the nuclei
      of HaCaT cells. Selective deficiency of NRF1 by lentiviral short-hairpin RNAs in
      HaCaT cells [NRF1-knockdown (KD)] led to decreased expression of gamma-glutamate
      cysteine ligase catalytic subunit (GCLC) and regulatory subunit (GCLM) and a
      reduced level of intracellular glutathione. In response to acute iAs3+ exposure,
      induction of some ARE-dependent genes, including NAD(P)H:quinone oxidoreductase 1
      (NQO1), GCLC, and GCLM, was significantly attenuated in NRF1-KD cells. However,
      the iAs3-induced expression of heme oxygenase 1 (HMOX-1) was unaltered by
      silencing NRF1, suggesting that HMOX-1 is not regulated by NRF1. In addition, the
      lack of NRF1 in HaCaT cells did not disturb iAs3+-induced NRF2 accumulation but
      noticeably decreased Kelch-like ECH-associated protein 1 (KEAP1) levels under
      basal and iAs3+-exposed conditions, suggesting a potential interaction between
      NRF1 and KEAP1. Consistent with the critical role of NRF1 in the transcriptional
      regulation of some ARE-bearing genes, knockdown of NRF1 significantly increased
      iAs3+-induced cytotoxicity and apoptosis. CONCLUSIONS: Here, we demonstrate for
      the first time that long isoforms of NRF1 contribute to arsenic-induced
      antioxidant response in human keratinocytes and protect the cells from acute
      arsenic cytotoxicity.

PMID- 20805063
TI  - Novel cytotoxic backbones and targeted therapies: recent data and ongoing
      clinical trials.
AB  - Novel therapies are emerging for treatment of patients with localized or advanced
      breast cancer. Targeted therapies such as trastuzumab, lapatinib, and bevacizumab
      have demonstrated significant clinical benefit in the metastatic setting, and
      trastuzumab has also improved patient outcome as adjuvant therapy in HER2+ breast
      cancer. Novel chemotherapies are also being developed to improve drug delivery,
      enhance efficacy, or decrease drug toxicity. These novel cytotoxic agents are
      being combined with established targeted therapies and are showing early promise
      for the treatment of patients with advanced breast cancer. Finally, new targeted
      therapies have shown clinical benefit, either as single agents or in combination
      with established targeted therapy or chemotherapy.

PMID- 20805064
TI  - Adjuvant taxanes: more to the story.
AB  - Breast cancer is a common public health problem, and the most important
      prognostic factors in survival or recurrence after potentially curative surgery
      include the number of involved axillary lymph nodes and the biology of the
      disease. Systemic chemotherapy remains a critical component in the eradication of
      occult micrometastatic disease in the adjuvant setting. The 2000 Early Breast
      Cancer Trialists' Collaborative Group overview of polychemotherapy in breast
      cancer has demonstrated that anthracycline-based regimens are superior to non
      anthracycline-based therapies in terms of disease-free survival and overall
      survival. The taxanes paclitaxel and docetaxel were well established in
      metastatic breast cancer and lack cross-resistance with anthracyclines and were
      therefore quickly deemed worthwhile for evaluation in the adjuvant setting. A
      large meta-analysis showed that the addition of a taxane to an anthracycline
      based regimen improves outcomes in high-risk patients regardless of age,
      menopausal status, number of nodes involved, hormone receptor status, and type of
      taxane. There are several effective anthracycline/taxane combinations
      traditionally studied in patients with high-risk disease. In this overview, we
      will review some of the key trials that have advanced the standard of care in the
      adjuvant setting with regard to various chemotherapy combinations.

PMID- 20805066
TI  - Challenges in applying recent clinical trial data to the care of patients.

PMID- 20805067
TI  - Algorithms for the treatment of patients with metastatic breast cancer and prior
      exposure to taxanes and anthracyclines.
AB  - At present, metastatic breast cancer (MBC) remains an incurable disease, with the
      goals of care aimed at maximizing the patient's duration and quality of life.
      Treatment options for a patient with MBC have become more efficacious and
      numerous. In addition to endocrine and chemotherapy agents, a number of targeted
      agents, including trastuzumab and bevacizumab, are available. The option to use
      novel agents combined with a multitude of standard chemotherapies has further
      enhanced the landscape of therapeutic options. As such, specific regimens must be
      evaluated within the framework of the individual patient, answering such
      questions as whether to treat with sequential single agents or combination
      regimens as well as which agents to use and in what sequence. The concept of
      personalized care is even more apparent in the setting of MBC, where the goal of
      palliation is intrinsically more nuanced than that of curative intent. This
      review will broadly assess the evidence for current treatment options with
      attention to varying clinical scenarios. Ultimately, delivering quality of care
      necessitates balancing an understanding of evidence-based data with sensitive
      attention to quality-of-life goals.

PMID- 20805068
TI  - An assessment of the economic impact of Local Boards of Health on West Virginia's
      economy.
AB  - West Virginia, as is true for the nation as a whole, spends far less on public
      health interventions than on curative care. In 2008 the United States spent
      approximately $2.4 trillion on healthcare, of which approximately $72 billion was
      allocated for public health activities-obviously a very small percentage (Centers
      for Medicare and Medicaid Services, U.S. Department of Heath and Human Services
      2010). In West Virginia the 2006 per capita budget allocation for Local Boards of
      Health (LBH) for Basic Public Health Services was about $6.91, and total public
      health funding was between $63 and $91 per capita depending on the definition of
      public health. At the same time, Medicaid expenditures by the State are
      approximately $269 per capita with total Medicaid expenditures around $995 per
      capita. The difference in funding for Medicaid is almost 10 times the amount
      allocated to public health. The funding differences between curative care and
      preventive care may not be the result of the public's lack of understanding of
      the benefits of prevention, but rather its focus on short term rather than long
      term economic benefits. For a state like West Virginia, in which per capita
      income is below the national average, Medicaid is good business for the State's
      economy. Far too often public health funding is viewed as a drain from a state's
      budget not as an economic contributor to the state's economy. As a result, the
      funding of LBHs is almost always insufficient. The authors were interested in
      evaluating the economic impact of Local Boards of Health on West Virginia's
      economy. Although the authors recognize that the greatest economic benefits of
      public health are the costs averted through prevention and early detection, they
      believe that if LBH produce a positive economic multiplier State officials may
      view public health allocations in a more positive light. To assess the impact of
      LBH in West Virginia, spending data for each was collected. The direct, indirect,
      and induced spending resulting from public health activity was considered. The
      results were modeled using the IMPLAN (IMPLAN Professional 1999) regional input
      output simulation software to assess the multiplier effects of direct LBH
      spending. Findings suggest that LBH produce a positive economic multiplier
      similar to other service industries in West Virginia. The inferences from this
      investigation focus on West Virginia however it is possible to make a reasonable
      argument that the fundamental issues are similar for states with similar
      economies.

PMID- 20805069
TI  - Summarizing green practices in U.S. hospitals.
AB  - The author used an Internet search to locate hospitals presently practicing green
      policies. She also included results from a Practice Greenhealth survey.
      Governmental antecedents and benefits of the green movement were also included.
      With limited documentation of the green movement in hospitals, the primary goal
      was to provide a compilation of policies and procedures that may be useful to
      hospitals considering the implementation of green practices. To that end,
      approximately 10 case hospitals were highlighted, along with a team of hospitals
      that collaborated on environmental and patient initiatives. The Practice
      Greenhealth survey of over 700 member hospitals highlighted additional progress
      that hospitals have achieved in the green movement.

PMID- 20805070
TI  - Cost of hospital-acquired infection.
AB  - The authors assessed the costs of hospital-acquired infections using rigorous
      econometric methods on publicly available data, controlling for the
      interdependency of length of stay and the incidence of hospital acquired
      infection, and estimated the cost shares of different payers. They developed a
      system of equations involving length of stay, incidence of infection, and the
      total hospital care cost to be estimated using simultaneous equations system. The
      main data came from the State of New Jersey UB 92 for 2004, complimented with
      data from the Annual Survey of Hospitals by the American Hospital Association and
      the Medicare Cost Report of 2004. The authors estimated that an incidence of
      hospital acquired infection increases the hospital care cost of a patient by
      $10,375 and it increases the length of stay by 3.30 days, and that a
      disproportionately higher portion of the cost is attributable to Medicare. They
      conclude that reliable cost estimates of hospital-acquired infections can be made
      using publicly available data. Their estimate shows a much larger aggregate cost
      of $16.6 billion as opposed to $5 billion reported by the Centers for Disease
      Control and Prevention but much less than $29 billion as reported elsewhere in
      the literature.

PMID- 20805071
TI  - Body mass composition: a predictor of admission outcomes among hospitalized
      Nigerian under 5 children.
AB  - BACKGROUND: Malnutrition remains a public health problem and a significant
      contributor to morbidity and mortality among children less than 5 years, in spite
      of global efforts at improving nutrition. OBJECTIVE: To examine the impact of
      nutritional status, by measured anthropometric indices and derived body
      composition, on disease outcomes in under-5 children hospitalised in an emergency
      unit. METHODS: All (n=164) consecutive children aged 12-59 months admitted into
      the Children Emergency Ward of the University College Hospital, Ibadan over a 3
      month period (May to July, 2007) had weight, length/height, mid upper arm
      circumference (MUAC) and skin fold thicknesses recorded. The BMI, Rohrer index, z
      scores for weight-for-height and weight-for-age were calculated. Malnutrition was
      defined as z scores<-2. Other derived parameters included Arm-Fat-Area (AFA), Arm
      Muscle-Area (AMA), Upper-Arm-Muscle-Estimate (UME), and Total-Upper-Arm-Area
      (TUA). Relative risk was calculated and logistic regression was used to determine
      which variables independently predict death. RESULTS: There were 153 survivors
      and 11 deaths giving an overall death rate of 6.7%. The mean age of survivors
      (26.7+/-12.5 months) compared with those who died (23.1+/-12.1 months) were
      similar (p>0.05). The risk of death was significantly higher among the
      malnourished compared with the well nourished. The TUA, AMA and UME of those who
      died were significantly lower than survivors' (p<0.05). MUAC remained an
      independent predictor of death among other measured and derived anthropometric
      indices. CONCLUSIONS: MUAC remains a useful anthropometric measurement for
      nutritional assessment and an independent predictor of survival among
      hospitalised under-5 children in Nigeria.

PMID- 20805072
TI  - Neonatal hypernatremia and dehydration in infants receiving inadequate
      breastfeeding.
AB  - INTRODUCTION: Neonatal hypernatermic dehydration (NHD) is a potentially very
      serious condition, which has been reported to occur in infants who have breast
      feeding problems in the first week of the life. This study looked at the
      incidence, risk factors, clinical symptoms and complications of NHD in healthy
      breastfed term neonates. METHODS: A prospective case-control study was conducted
      on 53 neonates with serum sodium concentrations of >or=150 mmol/L (as the case
      group) who were recruited between June 2006 and June 2007 from the Ghaem hospital
      (Mashhad, Iran) to investigate the relationship between NHD and breastfeeding.
      Fifty-three healthy breastfed full-term neonates (serum sodium<150 mmol/L) from
      the same hospital were also recruited as the control group. RESULT: The results
      showed an average weight loss of 1.6% in the healthy neonates vs. 16.2% in
      infants with NHD (p<0.001). The frequency of feeds received per day was 10.2 for
      the healthy neonates vs. 7.6 in the NHD group (p<0.001). The NHD group had
      mothers who had a higher frequency of breast problems (23 vs. 7, p<0.001). Mean
      serum sodium concentration was significantly lower in the control group compared
      with the cases (137.80 vs.160.06 mmol/L, p<0.001). The main presenting features
      of the infants with NHD were fever, lethargy and jaundice. CONCLUSION:
      Breastfeeding problems are associated with the presence of NHD. Therefore, more
      breast examination during prenatal and postnatal periods and careful neonatal
      weight watch during the first week of life could decrease the incidence of NHD.

PMID- 20805073
TI  - Effect of extrusion cooking and amylase addition to gruels to increase energy
      density and nutrient intakes by Vietnamese infants.
AB  - Extrusion cooking and amylase addition are two processing methods used for the
      preparation of high energy dense (ED) gruels of suitable consistency. A
      quantitative study of energy and nutrient intakes of 67 infants aged 6 to 10
      months in rural areas in Vietnam was carried out to compare the effects of these
      processes used alone or in combination. Twice a day, for a period of four days
      each, infants successively ate four gruels prepared from different flours based
      on a blend of rice, sesame and soybean: an instant flour obtained by extrusion
      cooking (gruel A), a ready-to-cook flour obtained by extrusion cooking plus alpha
      amylase addition (gruel B), a flour produced by milling crude rice, sesame and
      roasted soybean plus alpha-amylase addition (gruel C) and without amylase
      (control gruel D). Gruels A, B and C had a high ED of respectively 94, 122 and
      124 kcal/100 g while the control gruel D had a low ED (59 kcal/100 g). The
      intakes of the four gruels were inversely linked to their ED. However, despite
      the fact that gruels B and C had similar ED, larger intakes were obtained with
      gruel B, which was attributed to better acceptability. The average energy intakes
      of high ED gruels A, B and C, respectively 112, 134 and 117 kcal/meal, were
      significantly higher than that of gruel D (81 kcal/meal). Of the three processing
      methods, the one combining extrusion cooking and amylase addition gave the best
      results in terms of gruel acceptability and energy intake.

PMID- 20805074
TI  - Infant and toddlers' feeding practices and obesity amongst low-income families in
      Mexico.
AB  - The aim of this study was to determine the risk factors of childhood obesity
      among infants and toddlers from low-income families from three cities in Mexico.
      This is a cross-sectional study of mothers and their infants and toddlers
      attending a vaccination centre at three primary care clinics in Tijuana, Tuxtla,
      and Reynosa. Anthropometric measurements of the mothers and children were
      conducted at the clinic and a questionnaire was administered to the mother. Eight
      hundred and ten mothers and their 5 to 24 months old infants participated in the
      study. Average age for the mothers was 24 (21-28) years, and 57% of them were
      either overweight or obese. The children's average age was 12.7 (5-24) months.
      Overall overweight prevalence in this sample was 11% and obesity 8%, these
      increased with age, from 3% for overweight and 6 % for obesity before 6 months,
      to 13 and 10% between 12 to 24 months respectively. Thirty-five percent of
      infants were breastfed>or=6 month and 92% were introduced to other solid foods
      before 6 months. Introduction of high-fat content snacks (HFS) and carbonated and
      non-carbonated sweetened (CSD) drinks starts before 6 months and more than sixty
      percent of the children between 12 to 24 months of age were eating HFS and CSD
      sweetened drinks at least once a week. Consumption of snacks and CSD sweetened
      drinks (>or=1 week) was associated with being overweight and obese (crude), OR,
      1.82; 95% CI=1.24-2.65 (p=0.002). These results suggest that preventive programs
      should be initiated during pregnancy and continued.

PMID- 20805075
TI  - A study of calcium intake and sources of calcium in adolescent boys and girls
      from two socioeconomic strata, in Pune, India.
AB  - Adequate intake of calcium is important for skeletal growth. Low calcium intake
      during childhood and adolescence may lead to decreased bone mass accrual thereby
      increasing the risk of osteoporotic fractures. Our aim was to study dietary
      calcium intake and sources of calcium in adolescents from lower and upper
      economic strata in Pune, India. We hypothesized that children from lower economic
      strata would have lower intakes of calcium, which would predominantly be derived
      from non-dairy sources. Two hundred male and female adolescents, from lower and
      upper economic stratum were studied. Semiquantitative food frequency
      questionnaire was used to evaluate intakes of calcium, phosphorus, oxalic acid,
      phytin, energy and protein. The median calcium intake was significantly different
      in all four groups, with maximum intake in the upper economic strata boys (893
      mg, 689-1295) and lowest intake in lower economic strata girls (506 mg, 380-674).
      The median calcium intake in lower economic strata boys was 767 mg (585-1043) and
      that in upper economic strata girls was 764 mg (541-959). The main source of
      calcium was dairy products in upper economic strata adolescents while it was dark
      green leafy vegetables in lower economic strata adolescents. The median calcium
      intake was much lower in lower economic strata than in the upper economic strata
      both in boys and girls. Girls from both groups had less access to dairy products
      as compared to boys. Measures need to be taken to rectify low calcium intake in
      lower economic strata adolescents and to address gender inequality in
      distribution of dairy products in India.

PMID- 20805076
TI  - Towards the discovery of novel phytochemicals for disease prevention from native
      Australian plants: an ethnobotanical approach.
AB  - Investigation into phytochemicals from foods for disease prevention has increased
      substantially in the last few decades. However, a clear strategy on the selection
      of the most promising foods for research has been lacking. An ethnobotanical
      approach represents an effective method which may improve the outcomes of
      phytochemical research. Research on the health properties of native Australian
      plants is limited. The vast number of edible plants used as foods and medicines
      by the Australian Aboriginal population creates opportunities for the discovery
      of novel physiologically active compounds. Within this review, we propose an
      ethnobotanical approach to accelerate research towards the utilisation of native
      Australian plants for foods with health-enhancing properties.

PMID- 20805077
TI  - Vitamin B12 and folic acid supplementation and plasma total homocysteine
      concentrations in pregnant Indian women with low B12 and high folate status.
AB  - Maternal vitamin B12 deficiency and hyperhomocysteinemia predict poor pregnancy
      outcome, foetal adiposity and insulin resistance. In India amongst practicing
      clinicians and policy makers there is little appreciation of widespread vitamin
      B12 deficiency. We investigated 163 (86 rural, 77 urban) pregnant women attending
      antenatal clinics in a rural health centre and a referral hospital in the city of
      Pune, at 17, 28, and 34 weeks gestation for vitamin supplements, and circulating
      concentrations of vitamin B12, folate, and total homocysteine. At enrolment 80%
      rural and 65% urban women had low vitamin B12 but only two rural women had low
      folate concentrations. During pregnancy 85% rural and 95% of urban women received
      folic acid; 12% rural and 84% urban women also received vitamin B12. In women
      receiving no supplementation (n=17) plasma vitamin B12 and folate did not change
      from 17 to 34 weeks gestation, but homocysteine increased (p<0.05). Homocysteine
      concentrations at 34 weeks gestation in women receiving only folic acid (n=71,
      mean 8.4 (95% CI 7.8, 9.1) micromol/L) were comparable to the unsupplemented
      group (9.7 (7.3, 12.7), p=0.15), but women who received a total dose of >1000
      microg of vitamin B12 up to 34 weeks (n=42, all with folic acid) had lower
      concentrations (6.7 (6.0, 7.4), p<0.001). Increasing dose of vitamin B12 (rs=
      0.31, p=0.006) but not folic acid (rs=-0.19, p=0.11) was associated with lower
      plasma total homocysteine concentration. In vitamin B12 insufficient, folate
      replete pregnant women, vitamin B12 supplementation is associated with a
      reduction of plasma total homocysteine concentration in late pregnancy.

PMID- 20805078
TI  - Amino acid composition of lactating mothers' milk and confinement diet in rural
      North China.
AB  - This study was designed to investigate the amino acids composition of lactating
      mothers' milk and their confinement diet in a town in Northern China, as well as
      to assess the relation of amino acids content in human milk and diet. Forty
      lactating mothers age 19 to 35 years participated in the study. They were 4 to
      180 days postpartum. A 24-hour dietary recall was done and amino acids content of
      maternal milk was analyzed. The main findings are as follows: (1) The protein
      content of human milk is 1.58 g/dL and the ratio of EAA to NEAA is about 1:2. The
      most abundant amino acids in human milk are GLU (16.0%), PRO (10.2%), LEU (8.67%)
      and the lowest two are MET (1.76%) and TRP (0.91%). (2)The diet contains enough
      energy and protein, but lacks vitamins A, B and C, indicating that it is a
      characteristic confinement diet. Grain and eggs are the main source of protein,
      and soy and fish were consumed less frequently. (3) Amino acids composition in
      diet and milk are similar; and the correlation of the amino acids patterns
      between diet and milk is 0.989, demonstrating that the amino acid composition of
      diet is the foundation of that in human milk. However, almost no relation is
      found between the amino acids concentration in maternal diet and milk, suggesting
      that the amino acids content of the diet does not have a direct relation with
      that of human milk.

PMID- 20805079
TI  - Validity and reliability of skinfold measurement in assessing body fatness of
      Chinese children.
AB  - BACKGROUND: Validity and reliability of skinfold equations in estimating body fat
      in Chinese Children has not been documented. OBJECTIVE: Using Air Displacement
      Plethysmography (ADP) as a criterion, the validity and reliability of skinfold
      (SKF) measurement in predicting percent body fat (% fat) of Chinese children in
      Hong Kong were evaluated. DESIGN: 230 Chinese children in Hong Kong were
      recruited to participate in measurements of ADP, body height and weight, waist
      and arm circumferences, and skinfold (SKF) from different body sites. A sub
      sample of 41 participants was asked to take an additional measurement of Dual
      Energy X-ray Absorptiometry (DXA). % fat was measured from ADP, DXA, and
      estimated from Slaughter SKF equations. RESULTS: internal consistency of SKF and
      ADP measurements were very high (r>or=0.988). Significant difference was found
      between % fat Slaughter and % fat ADP (p<0.05). The Slaughter equations slightly
      underestimate %fat (boys: 1.52%; girls: 1.84%). The slope of the regression line
      for boys and both the slope and intercept of regression line for prepubescent
      girls were significantly different from the line of identity. Subsequent stepwise
      regression found the best model for boys includes predictors of height, and
      Sigma3SKF (triceps, calf, and suprailiac) (R2=0.88, see=3.70), and that for girls
      includes height, Sigma2SKF (triceps and calf), and waist circumference (R2=0.71,
      see=3.38). The most convenient model for both genders required only triceps and
      age (boys: R2=0.81, see=4.67; girls: R2=0.63, see=3.77). CONCLUSIONS: Skinfold
      measurements provide valid and reliable %fat estimation in Chinese children.
      However, the application of Slaughter equations in Chinese children is
      questionable. Alternative skinfold models are proposed.

PMID- 20805080
TI  - Behavioral control is an important predictor of soy intake in adults in the USA
      concerned about diabetes.
AB  - The primary objective of this study was to determine the variables associated
      with intention to consume soy products and identify key variables that could be
      used as targets in soy nutrition education and consumption promotion. A pre/post
      test survey was used during a three session class focused on diabetes that
      discussed and introduced soy foods. The Theory of Planned Behavior framed the
      questions and variables examined. Subjective norms and behavioral control were
      most important in predicting intention to consume soy foods. Specifically, health
      experts and providers were important subjective norms; accessibility and ability
      to prepare were key behavioural control determinants. While most participants
      tried soy during the program, taste and texture perceptions did not impact
      intention to buy soy in adults concerned about diabetes.

PMID- 20805081
TI  - Changes in body mass index among Tongan adults in urban and rural areas between
      the 1970s and 2000s.
AB  - The purpose of this study was to determine trends in body physique among Tongan
      adults, between the late 1970s and the 2000s. Two areas were studied: Kolofo'ou
      town (as an urban area) and 'Uiha village (as a rural area). Measurements of body
      weight and height were taken 4 times for all residents in both areas in 1977/79,
      1983, 1990, and 2001. The number of the subjects in 1977/1979, 1983, 1990, 2001
      were 130, 138, 102, 71 in the urban area and 92, 89, 90, 66 in the rural area
      respectively. The mean body mass index (BMI, kg/m2) values of males in the rural
      area increased significantly, from 28.0 kg/m2 in 1977 to 31.0 kg/m2 in 2001
      (p=0.001); in females, mean BMI values were 30.6 kg/m2 in 1977 and 33.3 kg/m2 in
      2001, this change was not statistically significant. However, the BMI values did
      not significantly change in males or females in the urban area. The proportion of
      rural males with a BMI>or=30 kg/m2 had increased from 24.5% in 1977 to 55.5% in
      2001 (p=0.012). Although the mean BMI values for males and females were higher in
      the urban area than in the rural area until 1990, the differences between the two
      areas were not observed in 2001, due to an increase of BMI in the rural area.
      Changes of the mean BMI values in the rural and urban areas studied, between the
      late 1970s and 2000s, were 10% and 4%, respectively.

PMID- 20805083
TI  - The association of carbohydrate intake, glycemic load, glycemic index, and
      selected rice foods with breast cancer risk: a case-control study in South Korea.
AB  - Despite carbohydrate hypothesis related to breast cancer development, the inter
      relationships of carbohydrate measures with risk of breast cancer are unclear. We
      evaluated the association between the risk of breast cancer and total
      carbohydrate intake, glycemic load, and glycemic index, and types of rice in a
      hospital-based case-control study. Cases were 362 women aged 30-65 years old who
      were histologically confirmed to have breast cancer. Controls visiting the same
      hospital were matched to cases according to their age (+/-2 years) and menopausal
      status. Food intake was estimated by a quantitative food frequency questionnaire
      (FFQ) with 121 items. Conditional and unconditional logistic regression analysis
      was used to obtain the odds ratios (ORs) and corresponding 95% confidence
      intervals. There were no associations between risk of breast cancer and
      carbohydrate intake and glycemic load. A positive association with white rice
      (OR=1.19 per 100g/d increment, 95% confidence interval (CI)=1.01-1.40), no
      association with mixed white rice (OR=0.95 per 100g/d increment, 95% CI=0.80
      1.13), and an inverse association with mixed brown rice (OR=0.76 per 100g/d
      increment of mixed brown rice, 95% CI=0.61-0.95) was found. Additional analysis
      showed a positive association for white rice and an inverse association f mixed
      brown rice with breast cancer risk among overweight, postmenopausal women. These
      results do not support an association between breast cancer and diets high in
      carbohydrate, glycemic index, or glycemic load. However, a higher consumption of
      mixed brown rice may be associated with a decreased risk of breast cancer,
      especially in overweight, postmenopausal women.

PMID- 20805082
TI  - Breakfast skipping as a risk correlate of overweight and obesity in school-going
      ethnic Fijian adolescent girls.
AB  - The prevalence of overweight and obesity has increased globally, and population
      data suggest that it is also increasing among ethnic Fijian youth. Among numerous
      behavioural changes contributing to overweight in youth residing in nations
      undergoing rapid economic and social change, meal skipping has not been examined
      as a potential risk factor. The study objectives were to assess the prevalence of
      overweight, obesity, and breakfast skipping and examine their cross-sectional
      association in a community sample of school-going ethnic Fijian adolescent girls
      (N=523). We measured height and weight, and assessed dietary patterns, eating
      pathology, dimensions of acculturation, and other socio-demographic and cultural
      data by self-report. We observed a high prevalence of both overweight (41%,
      including 15% who were obese) and breakfast skipping (68%). In addition, in
      multivariable analyses unadjusted for eating pathology, we found that more
      frequent breakfast skipping was associated with greater odds of overweight (odds
      ratio (OR)=1.15, confidence interval (CI)=1.06, 1.26, p<0.01) and obesity
      (OR=1.18, CI=1.05, 1.33, p<0.01). Regression models adjusting for eating
      pathology attenuated this relation so that it was non-significant, but
      demonstrated that greater eating pathology was associated with greater odds of
      both overweight and obesity. Future research is necessary to clarify the relation
      among breakfast skipping, eating pathology, and overweight in ethnic Fijian
      girls, and to identify whether breakfast skipping may be a modifiable risk factor
      for overweight in this population.

PMID- 20805084
TI  - Comparison of plasma and intake levels of antioxidant nutrients in patients with
      chronic obstructive pulmonary disease and healthy people in Taiwan: a case
      control study.
AB  - The imbalance of oxidant/antioxidant plays an important role in the development
      of chronic obstructive pulmonary disease (COPD). There is increasing evidence
      that individuals with high antioxidative nutrient levels in the diet or in blood
      tend to maintain better lung function. This study was conducted to determine
      whether COPD patients in Taiwan have lower plasma concentrations of antioxidative
      nutrients than do healthy people, and whether the dietary habits of COPD patients
      in Taiwan affect their intake of vitamin C and carotenoids. Thirty-four COPD
      patients and 43 healthy persons (with normal lung function) aged 50 years or
      older were recruited. Fasting venous blood was collected to measure
      concentrations of vitamins A, C, and E and carotenoids. Endogenous and H2O2
      induced additional DNA damage (markers of oxidative stress) in white blood cells
      were assayed. Dietary intakes of vitamin C and carotenoids were assessed by a
      food-frequency questionnaire. Compare to the healthy controls, COPD patients had
      significantly lower plasma concentrations of vitamins A, C, and E; alpha- and
      beta-carotene; and total carotenoids but significantly higher endogenous and H2O2
      induced white blood cell DNA damage. Intakes of vitamin C and several carotenoids
      were lower in the COPD group, and COPD patients consumed significantly fewer
      vegetables and fruits than did the healthy controls. In conclusion, COPD patients
      in Taiwan have lower levels of antioxidative nutrients in their plasma and diet
      than do healthy people. Intakes of vitamin C and carotenoids are correlated with
      dietary habits.

PMID- 20805085
TI  - A recycling index for food and health security: urban Taipei.
AB  - The modern food system has evolved into one with highly inefficient activities,
      producing waste at each step of the food pathway from growing to consumption and
      disposal. The present challenge is to improve recyclability in the food system as
      a fundamental need for food and health security. This paper develops a
      methodological approach for a Food Recycling Index (FRI) as a tool to assess
      recyclability in the food system, to identify opportunities to reduce waste
      production and environmental contamination, and to provide a self-assessment tool
      for participants in the food system. The urban Taipei framework was used to
      evaluate resource and nutrient flow within the food consumption and waste
      management processes of the food system. A stepwise approach for a FRI is
      described: (1) identification of the major inputs and outputs in the food chain;
      (2) classification of inputs and outputs into modules (energy, water, nutrients,
      and contaminants); (3) assignment of semi-quantitative scores for each module and
      food system process using a matrix; (4) assessment for recycling status and
      recyclability potential; (5) conversion of scores into sub-indices; (6)
      derivation of an aggregate FRI. A FRI of 1.24 was obtained on the basis of data
      for kitchen waste management in Taipei, a score which encompasses absolute and
      relative values for a comprehensive interpretation. It is apparent that a FRI
      could evolve into a broader ecosystem concept with health relevance. Community
      end-users and policy planners can adopt this approach to improve food and health
      security.

PMID- 20805086
TI  - Secular trends in growth and nutritional status of Vietnamese adults in rural Red
      River delta after 30 years (1976-2006).
AB  - In order to assess secular trends in growth of the Vietnamese population
      following a period of rapid economic growth, a follow-up study on physical growth
      and nutritional status of adults was carried out in a rural section of the Red
      River delta, Vietnam 30 years after the original study. The initial study in 1976
      found that average height and weight of Vietnamese adults was similar to data
      collected by French experts Huard and Bigot in 1938. Hence, no noticeable secular
      trends were observed in almost 40 years. However, the 2006 follow-up study
      revealed a positive secular trend in growth of adults, aged 16-60 years. The
      average increased rate in height of males was up to 1.1 cm/decade in the age
      group 26-40 years and up to 2.7 cm/decade in the age group 16-25 years.
      Nutritional status, as indicated by body mass index, increased in both sexes and
      in all age groups between 1976 and 2006.were observed. In 2006, average dietary
      intake of fat and animal protein was higher than that found in 1976. The
      percentage of energy from fat in the diet increased from 6% in 1976 to 16% in
      2006. This study shows that Vietnam is entering the nutrition transition period.

PMID- 20805087
TI  - Contribution of selected wild and cultivated leafy vegetables from South India to
      lutein and beta-carotene intake.
AB  - Carotenoids, especially lutein and beta-carotene, offer benefits to human health
      in general and to eye health in particular. However, more data on the
      contribution of plant foods to carotenoid intake is of importance for developing
      strategies for promoting eye health in regions where cataract is highly prevalent
      such as in South India. The most frequently consumed 5 uncultivated and 5
      commercially grown South Andhra Pradesh leafy vegetables were selected based on
      interviews with 100 local women. The lutein and beta-carotene contents of fresh
      and cooked samples were determined using reversed-phase high performance liquid
      chromatography. Lutein values ranged from 53 to 143 microg/g and 58 to 175
      microg/g in fresh and cooked samples, respectively. beta-carotene contents were
      found to range from 45 to 119 microg/g in fresh samples and from 40 to 159
      microg/g in cooked samples. No significant difference was observed between the
      carotenoid contents of wild and commercially grown species. According to their
      reported frequency of consumption, the 10 species considered in this study
      contribute 40% of the daily recommended intake of beta-carotene. This is the
      first report of lutein content in fresh samples of Celosia argentea L., Rumex
      vesicarius L., Digera muricata (L.) Mart., and Amaranthus cruentus L. as well as
      in cooked samples of all species included in this study.

PMID- 20805088
TI  - Relationships between body size and percent body fat among Melanesians in
      Vanuatu.
AB  - Obesity is a global epidemic, and measures to define it must be appropriate for
      diverse populations for accurate assessment of worldwide risk. Obesity refers to
      excess body fatness, but is more commonly defined by body mass index (BMI). Body
      composition varies among populations: Asians have higher percent body fat (%BF),
      and Pacific Islanders lower %BF at a given BMI compared to Europeans. Many
      researchers thus propose higher BMI cut-off points for obesity among Pacific
      Islanders and lower cut-offs for Asians. Because of the great genetic diversity
      in the Asia-Pacific region, more studies analyzing associations between BMI and
      %BF among diverse populations remain necessary. We measured height; weight;
      tricep, subscapular, and suprailiac skinfolds; waist and hip circumference; and
      %BF by bioelectrical impedance among 546 adult Melanesians from Vanuatu in the
      South Pacific. We analyzed relationships among anthropometric measurements and
      compared them to measurements from other populations in the Asia-Pacific region.
      BMI was a relatively good predictor of %BF among our sample. Based on regression
      analyses, the BMI value associated with obesity defined by %BF (>25% for men,
      >35% for women) at age 40 was 27.9 for men and 27.8 for women. This indicates a
      need for a more nuanced definition of obesity than provided by the common BMI cut
      off value of 30. Rather than using population-specific cut-offs for Pacific
      Islanders, we suggest the World Health Organization's public health action cut
      off points (23, 27.5, 32.5, 37.5), which enhance the precision of assessments of
      population-wide obesity burdens while still allowing for international
      comparison.

PMID- 20805089
TI  - Intake of dairy products and bone ultrasound measurement in late adolescents: a
      nationwide cross-sectional study in Japan.
AB  - INTRODUCTION: There is little evidence regarding the effects of dairy product
      intake on bone mineralization among late adolescents, especially in Asians. The
      aim of this study was to determine the association between dairy product intake
      and bone strength as measured by quantitative ultrasound (QUS) in a large
      Japanese population. METHODS: Subjects were 38,719 high school students (14,996
      males and 23,723 females) across 33 prefectures in Japan. Bone stiffness of the
      calcaneus was measured by QUS densitometry (AOS-100, Aloka). Subjects were given
      a self-administered questionnaire, which included questions on gender, age,
      height, weight, consumption of dairy products, and levels of physical activity.
      Intake of milk and yogurt were classified as none, 1-99, 100-199, 200-399,
      and>or=400 ml/day. RESULTS: The proportion of subjects who consumed milk 400
      ml/day or more was 21% in males and 7.3% in females, while 24% of males and 41.1%
      of females did not consume milk. After adjusting for physical activity, weight,
      gender, age, and area of residence, milk intake (R2=2.8%, p<0.0001) and yogurt
      intake (R2=0.1%, p<0.0001) were independently associated with the QUS
      measurement. Similar associations were found in males and females when a gender
      stratified analysis was conducted. CONCLUSION: We found a positive dose-effect
      relationship between milk intake and bone strength in late adolescents, to whom
      we recommend milk intake of 400 ml/day or more to obtain greater bone mass.

PMID- 20805090
TI  - Nutritional screening in community-dwelling older adults: a systematic literature
      review.
AB  - Nutrition screening is a process used to quickly identify those who may be at
      risk of malnutrition so that a full nutrition assessment and appropriate
      nutrition intervention can be provided. While many nutrition screening tools have
      been developed, few have been evaluated for use in older adults in the community
      setting. The aim of this paper is to determine the most appropriate nutrition
      screening tool/s, in terms of validity and reliability, for identifying
      malnutrition risk in older adults living in the community. Electronic databases
      MEDLINE, PUBMED, CINAHL and the Cochrane Library were searched for nutrition
      screening tools to identify malnutrition or under-nutrition for adults greater
      than 65 years living in the community. Ten screening tools were found for use in
      community-dwelling older adults and subjected to validity and/or reliability
      testing: Mini Nutritional Assessment-Short Form (MNA-SF), Malnutrition Universal
      Screening Tool (MUST), Nutrition Screening Initiative (NSI), which includes the
      DETERMINE Checklist and Level I and II Screen, Australian Nutritional Screening
      Initiative (ANSI), Seniors in the Community: Risk Evaluation for Eating and
      Nutrition (SCREEN I and SCREEN II), Short Nutritional Assessment Questionnaire
      (SNAQ), Simplified Nutritional Appetite Questionnaire (SNAQ), and two unnamed
      tools. MNA-SF appears to be the most appropriate nutrition screening tool for use
      in community-dwelling older adults although MUST and SCREEN II also have evidence
      to support their use. Further research into the acceptability of screening tools
      focusing on the outcomes of nutrition screening and appropriate nutrition
      intervention are required.

PMID- 20805091
TI  - Patient-centered design of an information management module for a personally
      controlled health record.
AB  - BACKGROUND: The development of health information technologies should be informed
      by iterative experiments in which qualitative and quantitative methodologies
      provide a deeper understanding of the abilities, needs, and goals of the target
      audience for a personal health application. OBJECTIVE: Our objective was to
      create an interface for parents of children with attention-deficit
      hyperactivity/disorder (ADHD) to enter disease-specific information to facilitate
      data entry with minimal task burden. METHODS: We developed an ADHD-specific
      personal health application to support data entry into a personally controlled
      health record (PCHR) using a three-step, iterative process: (1) a needs analysis
      by conducting focus groups with parents of children with ADHD and an heuristic
      evaluation of a prerelease version of a PCHR, (2) usability testing of an initial
      prototype personal health application following a "think aloud" protocol, (3)
      performance testing of a revised prototype, and (4) finalizing the design and
      functionality of the ADHD personal health application. Study populations for the
      three studies (focus groups and two usability testing studies) were recruited
      from organizations in the greater Boston area. Study eligibility included being
      an English- or Spanish-speaking parent who was the primary caretaker of a school
      age child with ADHD. We determined subjects' health literacy using the Test of
      Functional Health Literacy in Adults (TOFHLA). We assessed subjects' task burden
      using the National Aeronautics and Space Administration (NASA) Task Load Index.
      To assess the impact of factors associated with the time spent entering data, we
      calculated Pearson correlation coefficients (r) between time on task and both
      task burden and subject characteristics. We conducted t tests to determine if
      time on task was associated with successful task completion. RESULTS: The focus
      groups included three cohorts: 4 Spanish-speaking parents with diverse health
      literacy, 4 English-speaking parents with lower health literacy, and 7 English
      speaking parents with higher health literacy. Both the initial usability testing
      cohort (n = 10) and the performance-testing cohort (n = 7) included parents of
      diverse health literacy and ethnicity. In performance testing, the prototype
      PCHRs captured patient-specific data with a mean time on task of 11.9 minutes (SD
      6.5). Task burden experienced during data entry was not associated with
      successful task completion (P = .92). Subjects' past computer experience was
      highly correlated with time on task (r = .86, P = .01), but not with task burden
      (r = .18, P = .69). The ADHD personal health application was finalized in
      response to these results by (1) simplifying the visual environment, (2)
      including items to support users limited by health literacy or technology
      experience, and (3) populating the application's welcome screen with pictures of
      culturally diverse families to establish a personal family-oriented look and
      feel. CONCLUSIONS: Our patient-centered design process produced a usable ADHD
      specific personal health application that minimizes the burden of data entry.

PMID- 20805092
TI  - High-content assays for evaluating cellular and hepatic diacylglycerol
      acyltransferase activity.
AB  - Acyl-CoA:diacylglycerol acyltransferase (DGAT) catalyzes the terminal step in
      triglyceride (TG) synthesis using diacylglycerol (DAG) and fatty acyl-CoA as
      substrates. In the liver, the production of VLDL permits the delivery of
      hydrophobic TG from the liver to peripheral tissues for energy metabolism. We
      describe here a novel high-content, high-throughput LC/MS/MS-based cellular assay
      for determining DGAT activity. We treated endogenous DGAT-expressing cells with
      stable isotope-labeled [13C18]oleic acid. The [13C18]oleoyl-incorporated TG and
      DAG lipid species were profiled. The TG synthesis pathway assay was optimized to
      a one-step extraction, followed by LC/MS/MS quantification. Further, we report a
      novel LC/MS/MS method for tracing hepatic TG synthesis and VLDL-TG secretion in
      vivo by administering [13C18]oleic acid to rats. The [13C18]oleic acid
      incorporated VLDL-TG was detected after one-step extraction without conventional
      separation of TG and recovery by derivatizing [13C18]oleic acid for detection.
      Using potent and selective DGAT1 inhibitors as pharmacological tools, we measured
      changes in [13C18]oleoyl-incorporated TG and DAG and demonstrated that DGAT1
      inhibition significantly reduced [13C18]oleoyl-incorporated VLDL-TG. This DGAT1
      selective assay will enable researchers to discern differences between the roles
      of DGAT1 and DGAT2 in TG synthesis in vitro and in vivo.

PMID- 20805093
TI  - Combined use of experimental and computational screens to characterize protein
      stability.
AB  - One of the primary goals of protein design is to engineer proteins with improved
      stability. Protein stability is a key issue for chemical, biotechnology and
      pharmaceutical industries. The development of robust proteins/enzymes with the
      ability to withstand the potentially harsh conditions of industrial operations is
      of high importance. A number of strategies are currently being employed to
      achieve this goal. Two particular approaches, (i) directed evolution and (ii)
      computational protein design, are quite powerful yet have only recently been
      combined or applied and analyzed in parallel. In directed evolution, libraries of
      variants are searched experimentally for clones possessing the desired
      properties. With computational methods, protein design algorithms are utilized to
      perform in silico screening for stable protein sequences. Here, we used gene
      libraries of an unstable variant of streptococcal protein G (Gbeta1) and an in
      vivo screening method to identify stabilized variants. Many variants with notably
      increased thermal stabilities were isolated and characterized. Concomitantly,
      computational techniques and protein design algorithms were used to perform in
      silico screening of the same destabilized variant of Gbeta1. The combined use,
      and critical analysis, of these methods promises to advance the field of protein
      design.

PMID- 20805097
TI  - In vitro and in vivo effects of statins on platelet-activating factor and its
      metabolism.
AB  - Platelet activating factor (PAF) is implicated in cardiovascular disease (CVD).
      Statins are widely used in these situations. Therefore, we assessed their effect
      on the biological activities and metabolism of PAF. Several statins, including
      simvastatin, exhibited an inhibitory effect against PAF, comparable with that of
      PAF-inhibitors. Simvastatin also suppressed in vivo PAF-biosynthesis via the de
      novo pathway, in leukocytes of 6 simvastatin-treated volunteers. Total
      cholesterol and low-density lipoprotein cholesterol were also significantly
      decreased, whereas high-density lipoprotein cholesterol, triacylglycerol, EC(50),
      and lag time were unaffected in these participants. Simvastatin with an intact
      lactone ring also inhibited PAF-activities, while incubation of human mesangial
      cells with it also resulted in decreased de novo PAF-biosynthesis. This suggests
      that these simvastatin-dependent effects are independent of its lactone ring.
      These new actions of statins should be further studied in PAF-implicated
      pathological conditions such as CVD, cancer, and renal disease.

PMID- 20805095
TI  - Superoxide differentially controls pulmonary and systemic vascular tone through
      multiple signalling pathways.
AB  - AIMS: the aim of this study was to determine the relative importance of Ca(2+)
      sensitization, ion channels, and intracellular Ca(2+) ([Ca(2+)](i)) in the mixed
      constrictor/relaxation actions of superoxide anion on systemic and pulmonary
      arteries. METHODS AND RESULTS: pulmonary and mesenteric arteries were obtained
      from rat. Superoxide was generated in arteries and cells with 6-anilino-5,8
      quinolinequinone (LY83583). Following pre-constriction with U46619, 10 MUmol/L
      LY83583 caused constriction in pulmonary and relaxation in mesenteric arteries.
      Both constrictor and relaxant actions of LY83583 were inhibited by superoxide
      dismutase and catalase. LY83583 caused Rho-kinase-dependent constriction in alpha
      toxin-permeabilized pulmonary but not mesenteric arteries. Phosphorylation of
      myosin phosphatase-targeting subunit-1 (MYPT-1; as determined by western blot),
      was enhanced by LY83583 in pulmonary artery only. However, in both artery types,
      changes in tension were closely correlated with changes in phosphorylation of the
      20 kDa myosin light chain as well as changes in [Ca(2+)](i) (as measured with
      Fura PE-3), with LY83583 causing increases in pulmonary and decreases in
      mesenteric arteries. When U46619 was replaced by 30 mmol/L K(+), all changes in
      [Ca(2+)](i) were abolished and LY83583 constricted both artery types. The K(V)
      channel inhibitor 4-aminopyridine abolished the LY83583-induced relaxation in
      mesenteric artery without affecting constriction in pulmonary artery. However,
      LY83583 caused a similar hyperpolarizing shift in the steady-state activation of
      K(V) current in isolated smooth muscle cells of both artery types. CONCLUSIONS:
      superoxide only causes Rho-kinase-dependent Ca(2+) sensitization in pulmonary
      artery, resulting in constriction, and whilst it opens K(V) channels in both
      artery types, this only results in relaxation in mesenteric.

PMID- 20805096
TI  - What can we learn about cardioprotection from the cardiac mitochondrial proteome?
AB  - This review will summarize proteomic methods that are useful in studying the role
      of mitochondria in cardioprotection. The strengths and weaknesses of some of the
      different approaches are discussed. We focus on the cardiac mitochondrial
      proteome with emphasis on changes associated with cell death and protection, and
      we summarize how proteomic data have contributed to addressing the role of
      mitochondria in cardioprotection.

PMID- 20805098
TI  - Reduction of door-to-balloon time by new performance processes in patients with
      ST-segment elevation myocardial infarction undergoing primary percutaneous
      coronary intervention.
AB  - The aim of this study was to determine whether the adoption of new performance
      processes reduced the door-to-balloon time for primary percutaneous coronary
      intervention (PCI). To reduce the door-to-balloon time, we adopted 3 new
      performance processes: concurrent activation at the emergency department rather
      than stepwise activation; direct phone call rather than using a pager or message;
      patient transferred to catheterization laboratory before the PCI team arrive. A
      total of 139 consecutive patients were compared before and after the new
      performance processes. After the adoption of the new processes, median door-to
      balloon time reduced significantly from 133 to 76 minutes (P < .0001) and
      patients undergoing primary PCI within 90 minutes increased significantly from
      16% to 72% (P < .0001). Among the subdivisions of the door-to-balloon time, door
      to-consent time and door-to-laboratory arrival time decreased significantly (50.0
      vs 20.5 minutes, P < .0001; 95.0 vs 40.0 minutes, P < .0001, respectively).

PMID- 20805099
TI  - Cognition and olfaction in Parkinson's disease.

PMID- 20805100
TI  - Predicting a window of therapeutic opportunity in multiple sclerosis.

PMID- 20805094
TI  - EURObservational Research Programme: the Heart Failure Pilot Survey (ESC-HF
      Pilot).
AB  - AIMS: The primary objective of the new ESC-HF Pilot Survey was to describe the
      clinical epidemiology of outpatients and inpatients with heart failure (HF) and
      the diagnostic/therapeutic processes applied across 12 participating European
      countries. This pilot study was specifically aimed at validating the structure,
      performance, and quality of the data set, for continuing the survey into a
      permanent registry. METHODS AND RESULTS: The ESC-HF Pilot study is a prospective,
      multicentre, observational survey conducted in 136 cardiology centres from 12
      European countries selected to represent the different health systems and care
      attitudes across Europe. All outpatients with HF and patients admitted for acute
      HF were included during the enrolment period (1 day per week for 8 consecutive
      months). From October 2009 to May 2010, 5118 patients were included in this pilot
      survey, of which 1892 (37%) were admitted for acute HF and 3226 (63%) for chronic
      HF. Ischaemic aetiology was reported in about half of the patients. In patients
      admitted for acute HF, the most frequent clinical profile was decompensated HF
      (75% of cases), whereas pulmonary oedema and cardiogenic shock were reported,
      respectively, in 13.3 and 2.3% of the cases. The total in-hospital mortality rate
      was 3.8% and was cardiovascular in 90.1% of the cases. Lowest and highest
      mortality rates were observed in hypertensive HF and in cardiogenic shock,
      respectively. More than 80% of patients with chronic HF were treated with renin
      angiotensin-aldosterone system blockers and beta-adrenergic blockers. However,
      target doses of such drugs were reached in one-third to one-fourth of the
      patients only. CONCLUSION: The ESC-HF Pilot Survey is an example of the
      possibility of utilizing an observational methodology to get insights into the
      current clinical practice in Europe, whose picture will be completed by the 1
      year follow-up. Moreover, this study offered the opportunity to refine the
      organizational structure of a long-term, extended European network.

PMID- 20805101
TI  - Critical brain regions for action recognition: lesion symptom mapping in left
      hemisphere stroke.
AB  - A number of conflicting claims have been advanced regarding the role of the left
      inferior frontal gyrus, inferior parietal lobe and posterior middle temporal
      gyrus in action recognition, driven in part by an ongoing debate about the
      capacities of putative mirror systems that match observed and planned actions. We
      report data from 43 left hemisphere stroke patients in two action recognition
      tasks in which they heard and saw an action word ('hammering') and selected from
      two videoclips the one corresponding to the word. In the spatial recognition
      task, foils contained errors of body posture or movement amplitude/timing. In the
      semantic recognition task, foils were semantically related (sawing). Participants
      also performed a comprehension control task requiring matching of the same verbs
      to objects (hammer). Using regression analyses controlling for both the
      comprehension control task and lesion volume, we demonstrated that performance in
      the semantic gesture recognition task was predicted by per cent damage to the
      posterior temporal lobe, whereas the spatial gesture recognition task was
      predicted by per cent damage to the inferior parietal lobule. A whole-brain voxel
      based lesion symptom-mapping analysis suggested that the semantic and spatial
      gesture recognition tasks were associated with lesioned voxels in the posterior
      middle temporal gyrus and inferior parietal lobule, respectively. The posterior
      middle temporal gyrus appears to serve as a central node in the association of
      actions and meanings. The inferior parietal lobule, held to be a homologue of the
      monkey parietal mirror neuron system, is critical for encoding object-related
      postures and movements, a relatively circumscribed aspect of gesture recognition.
      The inferior frontal gyrus, on the other hand, was not predictive of performance
      in any task, suggesting that previous claims regarding its role in action
      recognition may require refinement.

PMID- 20805102
TI  - Blocking ADAM10 synaptic trafficking generates a model of sporadic Alzheimer's
      disease.
AB  - We describe here an innovative, non-transgenic animal model of Alzheimer's
      disease. This model mimics early stages of sporadic disease, which represents the
      vast majority of cases. The model was obtained by interfering with the complex
      between a disintegrin and metalloproteinase domain containing protein 10
      (ADAM10), the main alpha-secretase candidate, and its partner, synapse-associated
      protein 97, a protein of the postsynaptic density-membrane associated guanylate
      kinase family. Association of ADAM10 with synapse-associated protein 97 governs
      enzyme trafficking and activity at synapses. Interfering with the ADAM10/synapse
      associated protein 97 complex for 2 weeks by means of a cell-permeable peptide
      strategy is sufficient to shift the metabolism of the amyloid precursor protein
      towards amyloidogenesis and allows the reproduction of initial phases of sporadic
      Alzheimer's disease. After 2 weeks of treatment, we detected progressive
      Alzheimer's disease-like neuropathology, with an increase of beta-amyloid
      aggregate production and of tau hyperphosphorylation, and a selective alteration
      of N-methyl-d-aspartic acid receptor subunit composition in the postsynaptic
      compartment of mouse brain. Behavioural and electrophysiological deficits were
      also induced by peptide treatment.

PMID- 20805103
TI  - Postoperative statin therapy attenuates the intensity of systemic inflammation
      and increases fibrinolysis after coronary artery bypass grafting.
AB  - A total of 25 patients undergoing coronary artery bypass grafting (CABG) were
      included in the study. Patients received statin (20 mg daily) postoperatively for
      2 weeks. All analyses were performed at 2 different time points: preoperatively
      (group 1) and 2 weeks after operation (group 2). Interleukin (IL)-6, IL-8,
      plasminogen activator inhibitor 1 (PAI-1), tumor necrosis factor alpha (TNF
      alpha), tissue plasminogen activator (t-PA) levels, and tissue factor pathway
      inhibitor (TFPI) were evaluated. Statin treatment caused a significant reduction
      in the plasma level of PAI-1 (preop: 15.04 +/- 0.13 ng/mL vs postop: 13.89 +/-
      2.14 ng/mL; P < .05) and increased t-PA levels (preop: 109.74 +/- 0.13 vs postop:
      231.40 +/- 1.22 ng/mL; P < .001). Plasma TNF-alpha and IL-6 levels did not change
      with treatment. Statin treatment caused a significant reduction in plasma IL-8
      level (279.70 +/- 3.42 ng/mL vs postop: 207.18 +/- 3.63 ng/mL, P < .05), and TFPI
      (4.87 +/- 2.05 ng/mL vs postop: 6.27 +/- 1.25 ng/mL; P < .05). The results
      demonstrate that atorvastatin attenuates systemic inflammatory reaction after
      cardiac surgery.

PMID- 20805104
TI  - Preparing the nursing workforce of the future.
AB  - Nurse shortages coupled with the need for national healthcare reform present a
      challenge. We are not preparing enough nurses nor are we preparing nurses with
      the right skills to fully participate in a reformed healthcare system. Historical
      forces in nursing education have resulted in multiple levels of entry into
      nursing practice and an inadequate nursing workforce. Today's environment of
      expanding knowledge, the call for interdisciplinary healthcare delivery teams,
      and evidence of the relationship between nurse education and improved patient
      outcomes strongly indicate the need for nurses prepared at the baccalaureate
      level. Requiring a baccalaureate degree for entry into nursing practice, and as
      the initial degree of nursing education would prepare nurses earlier for graduate
      education and the much needed roles of educator, researcher and advanced practice
      nurse. The nursing profession should take the lead in advocating for educational
      policies that would adequately prepare the nurse workforce of the future.

PMID- 20805105
TI  - Synthetic associations in the context of genome-wide association scan signals.
AB  - Genome-wide association studies (GWAS) have successfully identified a large
      number of genetic variants associated with complex traits, but these only explain
      a small proportion of the total heritability. It has been recently proposed that
      rare variants can create 'synthetic association' signals in GWAS, by occurring
      more often in association with one of the alleles of a common tag single
      nucleotide polymorphism. While the ultimate evaluation of this hypothesis will
      require the completion of large-scale sequencing studies, it is informative to
      place it in the broader context of what is known about the genetic architecture
      of complex disease. In this review, we draw from empirical and theoretical data
      to summarize evidence showing that synthetic associations do not underlie many
      reported GWAS associations.

PMID- 20805107
TI  - Loss-of-function variants in the genomes of healthy humans.
AB  - Genetic variants predicted to seriously disrupt the function of human protein
      coding genes-so-called loss-of-function (LOF) variants-have traditionally been
      viewed in the context of severe Mendelian disease. However, recent large-scale
      sequencing and genotyping projects have revealed a surprisingly large number of
      these variants in the genomes of apparently healthy individuals--at least 100 per
      genome, including more than 30 in a homozygous state--suggesting a previously
      unappreciated level of variation in functional gene content between humans. These
      variants are mostly found at low frequency, suggesting that they are enriched for
      mildly deleterious polymorphisms suppressed by negative natural selection, and
      thus represent an attractive set of candidate variants for complex disease
      susceptibility. However, they are also enriched for sequencing and annotation
      artefacts, so overall present serious challenges for clinical sequencing projects
      seeking to identify severe disease genes amidst the 'noise' of technical error
      and benign genetic polymorphism. Systematic, high-quality catalogues of LOF
      variants present in the genomes of healthy individuals, built from the output of
      large-scale sequencing studies such as the 1000 Genomes Project, will help to
      distinguish between benign and disease-causing LOF variants, and will provide
      valuable resources for clinical genomics.

PMID- 20805108
TI  - Cohort profile: the Jamaican 1986 birth cohort study.

PMID- 20805106
TI  - Analysis of microRNA knockouts in mice.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that act as potent regulators of gene
      expression. The discovery of miRNAs with specific temporal and spatial expression
      patterns revealed a hidden layer of post-transcriptional gene regulation.
      Furthermore, differential expression of miRNAs during disease progression
      identified miRNAs as relevant candidate genes in human pathologies. Currently the
      exact roles of miRNAs in human development and disease progression remain largely
      unknown. There have been recent efforts to study the loss of these genes in vivo
      and this review will discuss published miRNA knockout mouse models, highlighting
      their potential mechanisms of action in vivo.

PMID- 20805109
TI  - Cohort profile: the Bambui (Brazil) Cohort Study of Ageing.

PMID- 20805110
TI  - Underestimated and under-recognized: the late consequences of acute coronary
      syndrome (GRACE UK-Belgian Study).
AB  - AIM: To define the long-term outcome of patients presenting with acute coronary
      syndrome [ST-segment elevation myocardial infarction (STEMI), and non-STEMI and
      unstable angina acute coronary syndrome (ACS) without biomarker elevation] and to
      test the hypothesis that the GRACE (Global Registry of Acute Coronary Events)
      risk score predicts mortality and death/MI at 5 years. METHODS AND RESULTS: In
      the GRACE long-term study, UK and Belgian centres prospectively recruited and
      followed ACS patients for a median of 5 years (1797 days). Primary outcome
      events: deaths, cardiovascular deaths (CVDs) and MIs. Secondary events: stroke
      and re-hospitalization for ACS. There were 736 deaths, 19.8% (482 CVDs, 13%) and
      347 (9.3%) MIs (>24 h), 261 strokes (7.7%), and 452 (17%) subsequent
      revascularizations. Rehospitalization was common: average 1.6 per patient; 31.2%
      had >1 admission, 9.2% had 5+ admissions. These events were despite high rates of
      guideline indicated therapies. The GRACE score was highly predictive of all-cause
      death, CVD, and CVD/MI at 5 years (death: chi(2) likelihood ratio 632; Wald
      709.9, P< 0.0001, C-statistic 0.77; for CVD C-statistic 0.75, P < 0.0001; CVD/MI
      C-statistic 0.70, P < 0.0001). Compared with the low-risk GRACE stratum (ESC
      Guideline criteria), those with intermediate [hazard ratio (HR) 2.14, 95% CI
      1.63, 2.81] and those with high-risk (HR 6.36, 95% CI 4.95, 8.16) had two- and
      six-fold higher risk of later death (Cox proportional hazard). A landmark
      analysis after 6 months confirmed that the GRACE score predicted long-term death
      (chi(2) likelihood ratio 265.4; Wald 289.5, P < 0.0001). Although in-hospital
      rates of death and MI are higher following STEMI, the cumulative rates of death
      (and CVD) were not different, by class of ACS, over the duration of follow-up
      (Wilcoxon = 1.5597, df = 1, P = 0.21). At 5 years after STEMI 269/1403 (19%)
      died; after non-STEMI 262/1170 (22%) after unstable angina (UA) 149/850 (17%).
      Two-thirds (68%) of STEMI deaths occurred after initial hospital discharge, but
      this was 86% for non-STEMI and 97% for UA. CONCLUSION: The GRACE risk score
      predicts early and 5 year death and CVD/MI. Five year morbidity and mortality are
      as high in patients following non-ST MI and UA as seen following STEMI. Their
      morbidity burden is high (MI, stroke, readmissions) and the substantial late
      mortality in non-STE ACS is under-recognized. The findings highlight the
      importance of pursuing novel approaches to diminish long-term risk.

PMID- 20805111
TI  - Reperfusion strategy in Europe: temporal trends in performance measures for
      reperfusion therapy in ST-elevation myocardial infarction.
AB  - AIMS: The rate and type of reperfusion, as well as time delays to reperfusion are
      directly associated with mortality and are established as performance measures
      (PMs) in the treatment of ST elevation myocardial infarction (STEMI). To date,
      little information exists about PMs for reperfusion in clinical practice in
      Europe and their temporal changes. METHODS AND RESULTS: Using the Euro Heart
      Survey ACS-III data set (2 years of inclusions between 2006 and 2008, 138 centres
      in 21 countries), we selected patients with STEMI eligible for reperfusion
      therapy. Recorded variables corresponded to the CARDS data set. The rate and type
      of reperfusion, as well as door to needle and door to artery times were assessed
      and compared between periods. Timely reperfusion was defined as a door to needle
      time < 30 min, or a door to artery time < 90 min. We assessed changes in PMs for
      reperfusion over the 2 years of recruitment. Among 19 205 patients included in
      the registry, 7655 had STEMI, and 6481 were admitted within the first 12 h and
      eligible for reperfusion. The rate of patients who underwent reperfusion
      increased from 77.2 to 81.3%, with an increase in the use of primary percutaneous
      coronary intervention (P-PCI). The door to needle and door to artery times
      decreased significantly during the study period, from 20 to 15 min (P = 0.0011)
      and from 60 to 45 min (P < 0.0001) respectively. As a result, the number of
      eligible patients receiving reperfusion therapy in a timely manner increased from
      53.1 to 63.5% (P < 0.0001). In parallel, over the 2-year period, in-hospital
      mortality decreased from 8.1 to 6.6% (P = 0.047). CONCLUSION: In centres
      participating in the Euro Heart Survey ACS III, PMs for reperfusion in STEMI
      improved significantly between 2006 and 2008, with greater use of PCI. Similarly,
      the rate of patients reperfused in a timely manner also increased, with a
      significant reduction in door to needle and door to artery times.

PMID- 20805112
TI  - COlchicine for the Prevention of the Post-pericardiotomy Syndrome (COPPS): a
      multicentre, randomized, double-blind, placebo-controlled trial.
AB  - AIMS: No drug has been proven efficacious to prevent the post-pericardiotomy
      syndrome (PPS), but colchicine seems safe and effective for the treatment and
      prevention of pericarditis. The aim of the COlchicine for the Prevention of the
      Post-pericardiotomy Syndrome (COPPS) trial is to test the efficacy and safety of
      colchicine for the primary prevention of the PPS. METHODS AND RESULTS: The COPPS
      study is a multicentre, double-blind, randomized trial. On the third post
      operative day, 360 patients (mean age 65.7 +/- 12.3 years, 66% males), 180 in
      each treatment arm, were randomized to receive placebo or colchicine (1.0 mg
      twice daily for the first day followed by a maintenance dose of 0.5 mg twice
      daily for 1 month in patients >=70 kg, and halved doses for patients <70 kg or
      intolerant to the highest dose). The primary efficacy endpoint was the incidence
      of PPS at 12 months. Secondary endpoint was the combined rate of disease-related
      hospitalization, cardiac tamponade, constrictive pericarditis, and relapses.
      Baseline characteristics were well balanced between the study groups. Colchicine
      significantly reduced the incidence of the PPS at 12 months compared with placebo
      (respectively, 8.9 vs. 21.1%; P = 0.002; number needed to treat = 8). Colchicine
      also reduced the secondary endpoint (respectively, 0.6 vs. 5.0%; P = 0.024). The
      rate of side effects (mainly related to gastrointestinal intolerance) was similar
      in the colchicine and placebo groups (respectively, 8.9 vs. 5.0%; P = 0.212).
      CONCLUSION: Colchicine is safe and efficacious in the prevention of the PPS and
      its related complications and may halve the risk of developing the syndrome
      following cardiac surgery. ClinicalTrials.gov number, NCT00128427.

PMID- 20805113
TI  - ISAR-REACT 3A: a study of reduced dose of unfractionated heparin in biomarker
      negative patients undergoing percutaneous coronary intervention.
AB  - AIMS: Although a 140 U/kg dose of unfractionated heparin (UFH) was comparable
      with bivalirudin in terms of net clinical outcome in the Intracoronary Stenting
      and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR
      REACT) 3 trial, it was associated with a higher risk of bleeding. We designed
      this study to assess whether a reduction in the UFH dose from 140 to 100 U/kg is
      associated with improved net clinical outcome. METHODS AND RESULTS: A total of
      2505 biomarker negative patients undergoing percutaneous coronary intervention
      (PCI) after clopidogrel pre-treatment received a single bolus of 100 U/kg UFH.
      The primary endpoint was net clinical outcome-a quadruple endpoint of death,
      myocardial infarction, urgent target-vessel revascularization within 30 days, or
      in-hospital REPLACE 2 defined major bleeding. The primary comparison was with the
      historical UFH group of ISAR-REACT 3 (2281 patients). In a second analysis, we
      checked for non-inferiority against the historical bivalirudin arm of ISAR-REACT
      3 (2289 patients). The incidence of the primary endpoint was 7.3% in the lower
      UFH dose group compared with 8.7% in the higher UFH dose group [hazard ratio (HR)
      0.81; 95% confidence interval (CI) 0.67-1.00; P = 0.045]. The incidence of major
      bleeding was 3.6% in the lower UFH dose group and 4.6% in the higher UFH dose
      group (HR 0.79; 95% CI 0.59-1.05; P = 0.11). The lower UFH dose met the criterion
      of non-inferiority compared with bivalirudin (P < 0.001). CONCLUSION: In
      biomarker negative patients undergoing PCI after clopidogrel loading, a reduced
      dose of 100 U/kg UFH provided net clinical benefit compared with the historical
      control of 140 U/kg UFH in the ISAR-REACT 3 trial. The benefit was mostly driven
      by reduction in bleeding. CLINICAL TRIAL REGISTRATION INFORMATION: URL
      www.clinicaltrials.gov; Unique identifier NCT00735280.

PMID- 20805114
TI  - Thrombin receptor antagonists may become an important antiplatelet therapy for
      coronary artery disease.

PMID- 20805117
TI  - The serum urate-lowering impact of weight loss among men with a high
      cardiovascular risk profile: the Multiple Risk Factor Intervention Trial.
AB  - OBJECTIVES: To evaluate the person-level impact of weight loss on serum urate
      levels among men with a high cardiovascular risk profile. METHODS: We analysed
      12,379 men (mean serum urate level=407 MUmol/l) from the Multiple Risk Factor
      Intervention Trial, using data prospectively collected at baseline and annually
      over a 7-year period (78,881 visits). Our endpoint was normouricaemia, defined by
      serum urate levels<=360 MUmol/l, a widely accepted therapeutic target. Person
      level effects were estimated using conditional logistic regression models to
      adjust for time-varying covariates (age, congestive heart failure, hypertension,
      diuretic use, renal function, alcohol intake and dietary factors). RESULTS: There
      was a graded relation between weight loss and achieving normouricaemia (P-value
      for trend<0.001). Compared with no weight change (-0.9 to 0.9 kg), the
      multivariate odds ratios of achieving normouricaemia for a weight loss of 1-4.9,
      5-9.9 and >=10 kg were 1.43 (95% CI: 1.33, 1.54), 2.17 (1.95, 2.40) and 3.90
      (3.31, 4.61), respectively. The corresponding serum urate level changes were -7, 
      19 and -37 MUmol/l (-0.12, -0.31 and -0.62 mg/dl). Similar levels of associations
      persisted among subgroups stratified by demographics, presence of gout,
      hypertension, diuretic use, renal insufficiency, alcohol intake, trial group
      assignment and adiposity categories (all P-values for trend<0.001). CONCLUSIONS:
      Weight reduction could help achieve a widely accepted therapeutic urate target
      level (<=360 MUmol/l) among men with a high cardiovascular risk profile. Although
      the urate-lowering effect appeared weaker than that of urate-lowering drugs,
      other associated health benefits would make weight reduction important,
      particularly in this population.

PMID- 20805115
TI  - Double-blind, placebo-controlled Phase II studies of the protease-activated
      receptor 1 antagonist E5555 (atopaxar) in Japanese patients with acute coronary
      syndrome or high-risk coronary artery disease.
AB  - AIMS: Two multicentre, randomized, double-blind, placebo-controlled Phase II
      studies assessed the safety and efficacy of the oral protease-activated receptor
      1 (PAR-1) antagonist E5555 in addition to standard therapy in Japanese patients
      with acute coronary syndrome (ACS) or high-risk coronary artery disease (CAD).
      METHODS AND RESULTS: Patients with ACS (n = 241) or high-risk CAD (n = 263)
      received E5555 (50, 100, or 200 mg) or placebo once daily for 12 (ACS patients)
      or 24 weeks (CAD patients). The incidence of TIMI major, minor, and minimal
      bleeds requiring medical attention was similar in the placebo and combined E5555
      (atopaxar) groups (ACS: 6.6% placebo vs. 5.0% E5555; CAD: 1.5% placebo vs. 1.5%
      E5555). There were no TIMI major bleeds and three CURE major bleeds (two with
      placebo; one with 100 mg E5555). There was a numerical increase in 'any' TIMI
      bleeding with the E5555 200 mg dose (ACS: 16.4% placebo vs. 23.0% E5555, P =
      0.398; CAD: 4.5% placebo vs. 13.2% E5555, P = 0.081). The rate of major
      cardiovascular adverse events in the combined E5555 group was not different from
      placebo (ACS: 6.6% placebo vs. 5.0% E5555, P = 0.73; CAD: 4.5% placebo vs. 1.0%
      E5555, P = 0.066). There was a statistically significant dose-dependent increase
      in liver function abnormalities and QTcF with E5555. At trough dosing levels in
      both populations, mean inhibition of platelet aggregation was > 90% with 100 and
      200 mg E5555, and 20-60% with 50 mg E5555. CONCLUSION: E5555 (50, 100, and 200
      mg) did not increase clinically significant bleeding, although there was a higher
      rate of any TIMI bleeding with the highest two doses. All doses tested achieved a
      significant level of platelet inhibition. There was a significant dose-dependent
      increase in liver function abnormalities and QTcF. Although further study is
      needed, PAR-1 antagonism may have the potential to be a novel pathway for
      platelet inhibition to add on to the current standard of care therapy.

PMID- 20805119
TI  - Impact of chronic kidney disease management in primary care.
AB  - BACKGROUND: The introduction of eGFR reporting and publication of national CKD
      guidelines has led to major challenges in primary and secondary care, leading to
      an increase in the number of referrals to nephrology clinics. We have shown that
      introduction of a renal patient care pathway reduces nephrology referrals and
      enables managed discharges of CKD patients to primary care. The aim of this
      article is to examine the outcome of patients discharged to primary care to find
      out if there is an associated risk with increased discharge supported by the
      patient pathway. METHODS: The study was carried out within a single NHS Trust
      covering a population of 560,000. All patients discharged from the trust's renal
      outpatient clinic between June 2007 and July 2008 were identified. Patient notes
      and the local laboratory database systems were used to determine the source and
      timing of tests. RESULTS: A total of 31 new referrals and 57 regular follow-ups
      were discharged during this period. The median age of discharge was 67.5 years.
      Most subjects (60%) had CKD stage 3 at the time of discharge. A total of 23% of
      discharges were categorized as CKD stages 1, 2 or normal and 17% of patients had
      CKD stage 4. Overall, 93% had stable eGFRs prior to discharge, 77.5% of patients
      had blood pressure within threshold (140/90 according to UK CKD guidelines) and
      97.7% of patients had haemoglobins >10 g/dl. Post-discharge 83% of patients had
      eGFRs recorded by their general practitioner and 92.6% of these were measured
      within appropriate time frames as per CKD guidelines. The majority of patients
      (82%) had either improved or stable eGFR post-discharge and only three patients
      had a significant decline in their eGFR. CONCLUSION: These data indicate that
      selected CKD patients can be appropriately discharged from secondary care and
      adequately monitored in primary care. Furthermore, we have shown that this was a
      safe practice for patients.

PMID- 20805120
TI  - Flying bedsheets.

PMID- 20805118
TI  - Inflammation and cancer: macrophage migration inhibitory factor (MIF)--the
      potential missing link.
AB  - Macrophage migration inhibitory factor (MIF) was the original cytokine, described
      almost 50 years ago and has since been revealed to be an important player in pro
      inflammatory diseases. Recent work using MIF mouse models has revealed new roles
      for MIF. In this review, we present an increasing body of evidence implicating
      the key pro-inflammatory cytokine MIF in specific biological activities related
      directly to cancer growth or contributing towards a microenvironment favouring
      cancer progression.

PMID- 20805121
TI  - Apparent motion photometry: evaluation and reliability of a novel method for the
      measurement of macular pigment.
AB  - BACKGROUND/AIMS: Macular pigment is thought to protect the macula against
      exposure to light and oxidative stress, both of which may play a role in the
      development of age-related macular degeneration. The aim was to clinically
      evaluate a novel cathode-ray-tube-based method for measurement of macular pigment
      optical density (MPOD) known as apparent motion photometry (AMP). METHODS: The
      authors took repeat readings of MPOD centrally (0 degrees ) and at 3 degrees 
      eccentricity for 76 healthy subjects (mean (+/-SD) 26.5+/-13.2 years, range 18-74
      years). RESULTS: The overall mean MPOD for the cohort was 0.50+/-0.24 at 0
      degrees , and 0.28+/-0.20 at 3 degrees  eccentricity; these values were
      significantly different (t=-8.905, p<0.001). The coefficients of repeatability
      were 0.60 and 0.48 for the 0 and 3 degrees  measurements respectively.
      CONCLUSIONS: The data suggest that when the same operator is taking repeated 0
      degrees  AMP MPOD readings over time, only changes of more than 0.60 units can be
      classed as clinically significant. In other words, AMP is not suitable for
      monitoring changes in MPOD over time, as increases of this magnitude would not be
      expected, even in response to dietary modification or nutritional
      supplementation.

PMID- 20805122
TI  - Oculometric alterations following intravitreal triamcinolone injection.

PMID- 20805116
TI  - Randomized trial to compare bilateral vs. single internal mammary coronary artery
      bypass grafting: 1-year results of the Arterial Revascularisation Trial (ART).
AB  - AIMS: Observational data suggest that the use of bilateral internal mammary
      arteries (BIMA) during coronary artery bypass graft surgery provides superior
      revascularization to a single internal mammary artery (SIMA), but concerns about
      safety have prevented the widespread use of BIMA. The Arterial Revascularisation
      Trial (ART) is a randomized trial of BIMA vs. SIMA, with a primary outcome of
      survival at 10 years. This paper reports mortality, morbidity, and resource use
      data at 1 year. METHODS AND RESULTS: Coronary artery bypass graft patients were
      enrolled in 28 hospitals in seven countries. Three thousand one hundred and two
      patients were randomly assigned to SIMA (n = 1554) or BIMA (n = 1548). The mean
      number of grafts was 3 for both groups. Forty per cent of the SIMA procedures and
      42% of the BIMA were performed off-pump. Mortality at 30 days was 18 of 1548
      (1.2%) for SIMA and 19 of 1537 (1.2%) for BIMA, and at 1 year was 36 of 1540
      (2.3%) and 38 of 1529 (2.5%), respectively. The rates of stroke, myocardial
      infarction, and repeat revascularization were all <=2% at 1 year and similar
      between the two groups. Sternal wound reconstruction was required in 0.6 and 1.9%
      of the SIMA and BIMA groups, respectively. CONCLUSION: Data from ART demonstrate
      similar clinical outcomes for SIMA and BIMA at 1 year but BIMA grafts are
      associated with a small absolute increase (1.3%) in the need for sternal wound
      reconstruction. The results suggest that the use of BIMA grafts is feasible on a
      routine basis. The 10-year results of the ART will confirm whether BIMA grafting
      results in lower mortality and the need for repeat intervention. TRIAL
      REGISTRATION: Controlled-trials.com (ISRCTN46552265).

PMID- 20805123
TI  - Evaluation of optical coherence tomography findings in age-related macular
      degeneration: a reproducibility study of two independent reading centres.
AB  - BACKGROUND/AIMS: To determine the reproducibility among readers of two
      independent certified centres, the Vienna Reading Center (VRC) and the University
      of Wisconsin-Madison Reading Center (UW-FPRC) for optical coherence tomography
      (OCT) images in age-related macular degeneration (AMD). METHODS: Fast macular
      thickness scans and 6&emsp14;mm cross hair scans were obtained from 100 eyes with
      all subtypes of AMD using Stratus OCT. Consensus readings were performed by two
      certified OCT readers of each reading center using their grading protocol. Common
      variables of both grading protocols, such as presence of cystoid spaces,
      subretinal fluid, vitreomacular traction and retinal pigment epithelial
      detachment, were compared using kappa statistics. In addition, the intraclass
      correlation coefficient (ICC) was calculated for centre point thickness (CPT) of
      values re-measured manually in the presence of alignment errors. RESULTS: The
      reproducibility was dependent on the variable measured with a kappa value of 0.81
      for the presence of cystoid spaces, 0.78 for the presence of subretinal fluid and
      0.795 for the presence of vitreomacular traction. The lowest reproducibility was
      found for the presence of retinal pigment epithelial detachment with a kappa
      value of 0.51. The CPT was re-measured in 29 out of 100 scans at both sites with
      an ICC of the re-measured thicknesses of 0.92. CONCLUSION: OCT scan data are
      crucial in monitoring treatment efficacy in AMD clinical trials. For comparison
      of results obtained by different reading centers, the inter-reading center
      reproducibility is essential. Although the reproducibility is generally high, the
      reliability depends on the selected morphological parameters.

PMID- 20805124
TI  - Forme fruste anterior segment dysgenesis.

PMID- 20805125
TI  - Comparing the ganglion cell complex and retinal nerve fibre layer measurements by
      Fourier domain OCT to detect glaucoma in high myopia.
AB  - AIM: To compare the diagnostic ability to detect glaucomatous changes between
      peripapillary retinal nerve fibre layer (RNFL) thickness and the macular ganglion
      cell complex (GCC) in highly myopic patients using Fourier domain optical
      coherence tomography. METHODS: Participants, consecutively enrolled from January
      2009 to June 2009, were imaged with RTVue-100 (NHM4 and MM7 scan). The
      sensitivity and specificity of a colour code less than 5% (red or yellow) for
      glaucoma diagnosis were calculated. Area under the receiver operator
      characteristic (AUROC) curves were generated to assess the ability of each
      parameter to detect glaucomatous changes. RESULTS: 73 normal controls and 77
      glaucoma patients were included. Participants were categorised as 105 non-high
      myopes (spherical equivalent >-6.0 dioptres) and 45 high myopes (Spherical
      equivalent <=-6.0 dioptres). The GCC thickness showed a strong correlation with
      RNFL thickness (correlation coefficient=0.763, p<0.001) in all participants. The
      sensitivity from superior GCC colour code was significantly higher than that from
      superior RNFL (p=0.019). The ability to detect glaucomatous changes in the highly
      myopic group by examining the average GCC thickness (AUROC, GCC; 0.889) was
      higher than when examining RNFL thickness (AUROC, RNFL; 0.825); however, there
      was no statistical significance (p=0.442). CONCLUSIONS: The ability to diagnose
      glaucoma with macular GCC thickness was comparable with that with peripapillary
      RNFL thickness in high-myopia patients. Macular GCC thickness measurements may be
      a good alternative or a complementary measurement to RNFL thickness assessment in
      the clinical evaluation of glaucoma in patients with high myopia.

PMID- 20805126
TI  - Hypothermia reduces secretion of vascular endothelial growth factor by cultured
      retinal pigment epithelial cells.
AB  - AIM: Visual loss in age-related macular degeneration usually develops secondary
      to choroidal neovascularisation. Vascular endothelial growth factor (VEGF) is a
      critical regulator of retinal angiogenesis and vascular permeability, especially
      in hypoxic conditions. We hypothesise that hypothermia may reduce the retinal
      pigment epithelium (RPE) metabolism and, consequently, the levels of VEGF
      secretion by cultured RPE cells under hypoxic conditions. The effects of
      hypothermia were compared with the metabolic inhibiting effects of thiopental and
      nicotinamide. METHODS: ARPE-19 cells were grown in culture for up to 5 days under
      normoxic (20% O(2)) and hypoxic (1% O(2)) conditions at temperatures ranging from
      27 degrees C to 40 degrees C. For experiments with pharmacological agents,
      thiopental and nicotinamide were added to the media. VEGF levels in the media
      were measured by ELISA and cell metabolic activity was measured by a fluorescent
      cell metabolic assay. RESULTS: We found that hypothermia reduced ARPE-19 cell
      metabolism in a temperature-dependent fashion. Hypothermia also reduced ARPE-19
      cell VEGF secretion in a temperature-dependent fashion. ARPE-19 cell VEGF
      secretion was reduced by 38% at 34 degrees C compared with cells grown at 37
      degrees C. Conversely, ARPE-19 cell VEGF secretion was increased by 32% at 40
      degrees C compared with cells grown at 37 degrees C. Hypoxia increased ARPE-19
      cell VEGF secretion by 84% at 37 degrees C. However, hypothermia decreased the
      hypoxia-induced increase of ARPE-19 cell VEGF secretion by 30%. The effect of
      hypothermia on ARPE-19 cell VEGF secretion was reversible after 4 days. In
      contrast to hypothermia, thiopental and nicotinamide were able to reduce RPE cell
      metabolism but not VEGF secretion. CONCLUSION: Hypothermia decreases both VEGF
      secretion and cellular metabolism in ARPE-19 cells. Hypothermia also mitigates
      the hypoxia-induced increase in ARPE-19 cell VEGF secretion. These effects of
      hypothermia are potentially unique and cannot be obtained by other
      pharmacological agents that slow cellular metabolism.

PMID- 20805127
TI  - Factors that correlate with improvement in vision after combined Intacs and trans
      epithelial corneal crosslinking.
AB  - AIM: To analyse factors that correlate with best corrected visual acuity (BCVA)
      improvement after Intacs and trans-epithelial corneal collagen crosslinking with
      riboflavin-carboxymethylcellulose. METHODS: A 3-year retrospective study of 14
      eyes that underwent trans-epithelial crosslinking and same day Intacs. RESULTS:
      The mean preoperative BCVA and spherical equivalent were significantly related to
      BCVA postoperatively. CONCLUSION: Poorer preoperative BCVA and spherical
      equivalent were associated with greater improvement in postoperative BCVA.

PMID- 20805128
TI  - Expression of MCSP and PRAME in conjunctival melanoma.
AB  - BACKGROUND: To analyse the expression of melanoma chondroitin sulfate
      proteoglycan (MCSP) and the preferentially expressed antigen of melanoma (PRAME)
      in conjunctival melanoma (CoM), lymph node (LN) metastases of cutaneous melanoma
      (CM) and conjunctival nevi (CoN) by immunohistology. METHODS: Immunohistology was
      performed in 70 samples of CoM, 25 of LN metastases of CM and 12 of CoN, and
      assessed by an immunoreactive score (0-12 points). Statistical analysis was
      performed to disclose relevant differences in the expression pattern. The
      diagnostic value of the markers was tested by receiver operating characteristics
      (ROC) analysis. RESULTS: MCSP and PRAME were expressed at significantly higher
      levels in CoM and LN metastases of CM than in CoN (p<0.0001). Within CoM, an MCSP
      expression <9.0 points meant higher risk for recurrences (Cox HR=3.1) and a
      shorter recurrence-free survival (p=0.002) than an MCSP expression >9.0 points.
      ROC analysis showed an area under the curve of 91.3% for MCSP (p=0.0002) and
      93.8% for PRAME (p<0.0001). CONCLUSIONS: MCSP and PRAME are differentially
      expressed in conjunctival melanomas and nevi. MCSP might have an impact on the
      risk for recurrence in being inversely correlated to the event. Both markers have
      high potential to discriminate CoM from CoN. The results indicate that
      immunohistological characteristics gain relevance in the assessment of CoM.

PMID- 20805129
TI  - Characterisation of the phenotype and function of monocyte-derived dendritic
      cells in allergic conjunctiva.
AB  - BACKGROUND: Dendritic cells (DCs) are the most potent antigen-presenting cells
      involved in initiating the immune response, presenting antigens to T cells and
      leading to T cell proliferation. In an immature state, DCs lack accessory signals
      required for T cell stimulation but are highly specialised to capture antigens.
      Full DC maturation changes the cell surface phenotype and facilitates stimulation
      of T cell proliferative responses. To examine the degree of DC maturity
      associated with vernal keratoconjunctivitis (VKC), the authors examined the
      phenotype and antigen-presentation capability of blood derived DCs from VKC
      patients and from normal controls. METHODS: Flow cytometry was used to identify
      the cell surface expression of markers of DC maturity (CD83, CD86, major
      histocompatibility complex class II) and mixed leucocyte reactions to assess DC
      induction of T cell proliferation. RESULTS: DCs derived from VKC patients were of
      a more mature phenotype than those from normal controls. However, these VKC DCs
      had reduced capability for induction of T cell proliferation compared with DCs
      from controls. CONCLUSION: The increased maturity of DCs in VKC patients
      correlates with the heightened immune responsiveness associated with this
      disorder. A number of mechanisms may underlie the impaired ability of DCs in
      atopy to stimulate T cell proliferation. This impairment of DC induction of T
      cell activation is likely to be one factor which contributes to the modified
      inflammatory response seen in VKC patients and the recognised susceptibility of
      these patients to viral infection.

PMID- 20805130
TI  - Causes of cataract surgery malpractice claims in England 1995-2008.
AB  - AIMS: To analyse the causes of malpractice claims related specifically to
      cataract surgery in the National Health Service in England from 1995 to 2008.
      METHODS: All the malpractice claims related to cataract surgery from 1995 to 2008
      from the National Health Service Litigation Authority were analysed. Claims were
      classified according to causative problem. Total numbers of claims, total value
      of damages, mean level damages and paid:closed ratio (a measure of the likelihood
      of a claim resulting in payment of damages) were determined for each cause.
      RESULTS: Over the 14-year period, there were 324 cataract surgery claims with
      total damages of L 1.97 million and mean damages for a paid claim of L 19,900.
      Negligent surgery (including posterior capsule tear and dropped nucleus) was the
      most frequent cause for claims, while reduced vision accounted for the highest
      total and mean damages. Claims relating to biometry errors/wrong intraocular lens
      power were the second most frequent cause of claims and result in payment of
      damages in 62% of closed cases. The claims with the highest paid:closed ratio
      were inadequate anaesthetic (75%) and complications of anaesthetic injections
      including globe perforation (67%). CONCLUSIONS: Claims from cataract surgery in
      the NHS are extremely infrequent. Consent, though essential, may not prevent a
      claim arising or resulting in damages. Refractive accuracy has significant
      medicolegal impact. Endophthalmitis can lead to successful claims if there is
      delay in diagnosis. Claims relating to inadequate anaesthesia or anaesthetic
      injection complications are particularly hard to defend.

PMID- 20805131
TI  - Position of retinal blood vessels correlates with retinal nerve fibre layer
      thickness profiles as measured with GDx VCC and ECC.
AB  - AIM: To evaluate the correlation of the retinal blood vessel position and the
      retinal nerve fibre layer (RNFL) thickness profile. METHODS: RNFL thickness of 81
      healthy subjects was measured using scanning laser polarimetry (SLP). To quantify
      the retinal blood vessel position, the angle (superior and inferior) between a
      horizontal line and a line from the optic disc centre to the intersection of the
      most temporal major retinal blood vessel and the outer margin of the measurement
      ellipse was measured on the SLP printout. RESULTS: A negative correlation was
      found between both the superior and inferior angle and the superotemporal and
      inferotemporal RNFL thickness, and a positive correlation between both angles and
      the superonasal and inferonasal RFNL thickness. The steepest slope of the
      regression line was located in the superotemporal and inferotemporal regions (
      0.7 to -1.0 MUm/ degrees ). Using this slope, the difference in RNFL thickness
      for the interquartile range of the superior angle was 13 MUm. CONCLUSION: RNFL
      thickness profiles correlate with the location of the main temporal superior and
      inferior blood vessels. The application of a normative database, taking into
      account the position of major blood vessels, might improve the diagnostic power
      of RNFL measurement.

PMID- 20805132
TI  - 'A bottle of intraoperative floppy iris pills please, pharmacist'.

PMID- 20805133
TI  - Ophthalmological findings in children and adolescents with Silver-Russell
      syndrome.
AB  - AIM: To evaluate ophthalmological findings in children with Silver-Russell
      syndrome (SRS). METHODS: An ophthalmological evaluation including visual acuity
      (VA), refraction, strabismus, near point of convergence (NPC), slit-lamp
      examination, ophthalmoscopy, axial length measurements and full-field
      electroretinogram was performed on 18 children with SRS (8 girls, 10 boys; mean
      age 11.6 years). Fundus photographs were taken for digital image analysis. Data
      were compared with data on an age- and gender-matched reference group (ref) of
      school children (n=99). RESULTS: Seventeen out of 18 children with SRS had
      ophthalmological abnormalities. Best corrected VA of the best eye was <0.1 log of
      the minimal angle of resolution in 11 children (ref n=98) (p<0.0001), and 11
      children had refractive errors (ref n=33) (p=0.05). Anisometropia (>=1 dioptre)
      was noted in three of the children (ref n=3) (p=0.046). Subnormal stereo acuity
      and NPC were found in 2/16 (ref=0) (p=0.02). The total axial length in both eyes
      was shorter compared with that in controls (p<0.006 and p<0.001). Small optic
      discs were found in 3/16, large cup in 3/16 and increased tortuosity of retinal
      vessels in 4/13 children with SRS. CONCLUSION: Children with SRS, who are
      severely intrauterine growth retarded, show significant ophthalmological
      abnormalities. Based on the present findings, ophthalmological examination is
      recommended in children with SRS.

PMID- 20805134
TI  - In vivo analysis of conjunctiva in gold micro shunt implantation for glaucoma.
AB  - AIMS: To describe the conjunctival epithelial features seen with in vivo confocal
      microscopy (IVCM) after gold micro shunt (GMS) implantation in the suprachoroidal
      space, in patients with uncontrolled glaucoma. METHODS: This was an observational
      case series study. Fourteen eyes of 14 consecutive glaucomatous patients with a
      history of multiple failed incisional surgeries followed by GMS implantation were
      evaluated with a digital confocal laser-scanning microscope (HRT II Rostock
      Cornea Module). Patients were divided into two groups: successful implantations
      (Group 1: eight patients, eight eyes), defined as a one-third reduction in
      preoperative intraocular pressure (IOP) with or without antiglaucoma medications
      and failed implantations (Group 2: six patients, six eyes) as a less than one
      third reduction in preoperative IOP with maximal tolerated medical therapy. The
      examination was performed from 3 to 20 months (mean 15.4+/-5.4) postoperatively.
      Conjunctival mean microcyst density (MMD: cysts/mm(2)) and mean microcyst area
      (MMA: MUm(2)) were the main outcome measurements. RESULTS: The mean postoperative
      IOP was statistically different between the two groups (p<0.05), with the values
      of 14.3+/-2.77 and 32.3+/-8.01 mm Hg in Groups 1 and 2, respectively. When
      comparing successful with failed implantation, the IVCM analysis showed a greater
      MMD (p<0.01) and MMA (p<0.01). Clinical evidence of filtering bleb was not found
      in any of the patients. CONCLUSIONS: Successful GMS implantation significantly
      increased conjunctival microcysts density and surface at the site of the device
      insertion. These findings suggest that the enhancement of the aqueous filtration
      across the sclera may be one of the possible outflow pathways exploited by the
      shunt.

PMID- 20805135
TI  - The effects of midazolam on intraocular pressure in children during examination
      under sedation.
AB  - BACKGROUND: To obtain reliable and accurate measurements of the intraocular
      pressure (IOP) in children often requires sedation or anaesthesia. Therefore, we
      investigated the effects of oral midazolam on IOP in children. METHODS: In a
      prospective study, IOP was measured in 72 eyes of 36 cooperative children without
      glaucoma requiring general anaesthesia (mean age 3.5+/-1.3 years, body weight
      <=20 kg) by using a Perkins hand-held tonometer. Measurements of IOP were
      performed before, and 15 and 30 min after sedation with orally administered
      midazolam (1 mg/kg) given as preoperative medication, and 5 and 15 min after
      induction of general anaesthesia. The individual IOP courses were analysed.
      RESULTS: In all of the cooperative children, IOP measurement was possible after
      sedation with midazolam. Mean IOP was 11.2+/-0.3 mmHg before sedation, 10.9+/-0.2
      mmHg at 15 min, and 10.7+/-0.3 mmHg 30 min after administration of midazolam.
      This small decrease was not statistically significant, whilst the IOP decline at
      5 and 15 min after induction of general anaesthesia was statistically significant
      (p<0.0001). CONCLUSION: Sedation with midazolam can be assumed to be an
      applicable, well-tolerated, safe method for IOP measurements in children.

PMID- 20805136
TI  - Analysis of GNAQ mutations, proliferation and MAPK pathway activation in uveal
      melanomas.
AB  - AIM: To study the GNAQ mutational status in a series of uveal melanomas and
      evaluate possible associations with mitogen-activated protein kinase (MAPK)
      pathway protein expression and tumour proliferation markers. METHODS: Mutational
      analysis was performed by PCR/sequencing of exon 5 of the GNAQ gene in a series
      of 22 uveal melanomas in which total and phosphorylated extracellular signal
      regulated kinase (ERK) 1/2 overexpression without coexistent BRAF and NRAS
      mutations had previously been observed. Expression of the cell cycle markers (Ki
      67, cyclin D1 and p27) was evaluated by immunohistochemistry. The association
      between GNAQ mutational status, ERK1/2, phospho-ERK1/2, Ki-67, cyclin D1 and p27
      expression levels and the clinicopathological prognostic parameters of uveal
      melanomas was also assessed. RESULTS: GNAQ mutations were found in 36% of uveal
      melanomas. No associations were found between the GNAQ mutational status and
      prognostic parameters, the expression of ERK1/2, pERK1/2 and cell cycle markers.
      CONCLUSION: The results of this study suggest that GNAQ mutated uveal melanomas
      do not exhibit a higher deregulation of proliferation or higher activation of the
      MAPK signalling pathway than uveal melanomas without GNAQ overactivation.

PMID- 20805137
TI  - Comparison of prognostic value of Roper Hall and Dua classification systems in
      acute ocular burns.
AB  - AIM: To compare the predictive outcome of ocular burns using two different
      prognostic classification systems, that is, Dua and Roper Hall classification.
      PATIENTS AND METHODS: In a prospective, randomised, controlled clinical trial,
      the extent of acute ocular burns in 100 patients was graded by Roper Hall and Dua
      classifications. Patients were randomised in two groups of 50 each to receive
      conventional medical therapy alone or additional amniotic membrane
      transplantation (AMT). Moderate burns were graded similarly (grade II and III)
      under both systems, while severe burns were classified differently and compared
      further. Baseline parameters (size of epithelial defect, corneal haze, limbal
      ischaemia, conjunctival involvement and visual acuity) and outcome variables
      (healing of epithelial defect, corneal clarity, corneal vascularisation, visual
      outcome and symblepharon) after 1&emsp14;year were noted and compared. RESULTS:
      There was no difference in terms of time taken and rate of healing of epithelial
      defect, but there was a significant difference in extent of corneal
      vascularisation between grades IV, V and VI (p<0.05). In patients who received
      AMT in addition to medical therapy, the degree of corneal clarity achieved was
      significantly better in patients with grade IV burns than either grade V
      (p=0.045) or grade VI (p=0.024) burns, and final visual acuity was significantly
      better in these patients (p=0.043). On comparison of patients with grade IV burns
      (with and without AMT), the outcome in terms of extent of corneal vascularisation
      was significantly better (p=0.0124) in patients who received AMT. CONCLUSIONS:
      Dua classification by providing further subclassification of grade IV ocular
      burns by Roper Hall into three separate grades has a superior prognostic
      predictive value in severe ocular burns.

PMID- 20805138
TI  - Alzheimer's disease and glaucoma.

PMID- 20805139
TI  - Familial vitreous amyloidosis linked with factor V Leiden deficiency.

PMID- 20805140
TI  - In vivo confocal microscopy of the ocular surface: from bench to bedside and back
      again.

PMID- 20805141
TI  - Relationship between the metallurgical structure of experimental titanium
      miniscrew implants and their torsional properties.
AB  - The aims of this study were to investigate the torsional properties of three
      experimental titanium miniscrew implants for orthodontic anchorage and to
      determine the relationship between the torsional properties and metallurgical
      structures. Experimental miniscrew implants with a diameter of 1.4 mm were
      fabricated from commercially pure (CP) titanium (alpha-titanium), Ti-4Al-4V
      (duplex alpha-beta-titanium), and Ti-33Nb-15Ta-6Zr (beta-titanium). Micro-X-ray
      diffraction (XRD) was performed to identify phases, and microstructures of etched
      cross-sections were obtained with scanning electron microscopy (SEM). Implants
      were loaded in torsion (n = 5), and mean moments and twist angles at fracture
      were statistically compared using the Kruskal-Wallis and Mann-Whitney U-tests.
      Cyclic torsional moment for fracture of starting square wires (2 * 2 * 30 mm) was
      measured (n = 3). At fracture, the Ti-4Al-4V and Ti-33Nb-15Ta-6Zr implants
      demonstrated significantly higher mean torque than the CP titanium implant, while
      the Ti-33Nb-15Ta-6Zr implant had a significantly higher mean twist angle than the
      other two implants. The CP titanium and Ti-33Nb-15Ta-6Zr implants displayed good
      fatigue performance and excellent ductility. Ti-33Nb-15Ta-6Zr beta-titanium alloy
      is suitable for manufacturing miniscrew implants since it has excellent torsional
      properties.

PMID- 20805142
TI  - Bond strength of orthodontic light-cured resin-modified glass ionomer cement.
AB  - The purpose of this study was to compare the bond strengths and debonded
      interfaces achieved with light-cured resin-modified glass ionomer cement (RMGIC)
      and conventional light-cured composite resin. In addition, the effects of acid
      etching and water contamination were examined. One hundred human premolars were
      randomly divided into five equal groups. The mini Dyna-lock upper premolar
      bracket was selected for testing. The first four groups were treated with light
      cured RMGIC with or without 15 per cent phosphoric acid-etching treatment and
      with or without water contamination preceding bracket bonding. The control
      samples were treated with the conventional light-cured Transbond composite resin
      under acid etching and without water contamination. Subsequently, the brackets
      were debonded by tensile force using an Instron machine. The modified adhesive
      remnant index (ARI) scores were assigned to the bracket base of the debonded
      interfaces using a scanning electron microscope. The bond strength and modified
      ARI scores were determined and analysed statistically by one-way analysis of
      variance and chi-square test. Under all four conditions, the bond strength of the
      light-cure RMGIC was equal to or higher than that of the conventional composite
      resin. The highest bond strength was achieved when using RMGIC with acid etching
      but without water contamination. The modified ARI scores were 2 for Fuji Ortho LC
      and 3 for Transbond. No enamel detachment was found in any group. Fifteen per
      cent phosphoric acid etching without moistening the enamel of Fuji Ortho LC
      provided the more favourable bond strength. Enamel surfaces, with or without
      water contamination and with or without acid etching, had the same or a greater
      bond strength than Transbond.

PMID- 20805143
TI  - Policy statement--recommendations for prevention and control of influenza in
      children, 2010-2011.
AB  - The purpose of this statement is to update current recommendations for routine
      use of trivalent seasonal influenza vaccine and antiviral medications for the
      prevention and treatment of influenza in children. The 2009 influenza A (H1N1)
      pandemic virus is expected to circulate, with infants and children at increased
      risk of severe illness and death. This year's trivalent seasonal influenza
      vaccine contains A/California/7/2009 (H1N1)-like antigen (derived from the 2009
      pandemic influenza A [H1N1] virus); A/Perth/16/2009 (H3N2)-like antigen; and
      B/Brisbane/60/2008-like antigen. Pediatricians continue to have a leadership role
      in the prevention of influenza through vaccine use and public education. In
      addition, pediatricians should promptly identify influenza infections to enable
      rapid treatment of influenza, when indicated, to reduce childhood morbidity and
      mortality.

PMID- 20805144
TI  - A national study of physician recommendations to initiate and discontinue growth
      hormone for short stature.
AB  - OBJECTIVES: Overall growth hormone (GH) use depends on decisions to both initiate
      treatment and continue treatment. The determinants of both are unclear. We
      studied how physicians decided to begin GH in idiopathic short stature and how,
      after an initial course of treatment, they decided to continue, intensify
      (increase the dose), or terminate treatment. METHODS: We used a national census
      study of 727 pediatric endocrinologists involving a structured questionnaires
      with a factorial experimental design. Main outcome measures were GH
      recommendations for previously untreated children and those children who were
      treated with GH for 1 year. RESULTS: The response rate was 90%. In previously
      untreated children, recommendations to initiate GH were consistent with
      guidelines and also influenced by family preferences and physician attitudes
      (P<.001). In children treated with GH, recommendations on whether to continue GH
      were influenced by the growth response to therapy (P<.01) but were divided
      regarding course of action. With identical growth responses to treatment,
      physician decisions diverged (intensify versus discontinue GH) and were driven by
      independent, nonphysiologic, and contextual factors (eg, physician attitudes,
      family preferences, and GH-initiation recommendation; each P<.001). Together,
      attitudinal and contextual factors exerted more influence on continuation
      decisions than did the growth response to therapy. CONCLUSIONS: Physician
      decisions to initiate GH are largely consistent with evidence-based medicine.
      However, decisions about continuing GH vary and are strongly influenced by
      factors other than response to treatment. With a potential market of 500 000 US
      children and costs exceeding $10 billion per year, changes in GH use may depend
      on potentially modifiable physician attitudes and family preferences as much as
      physiologic evidence.

PMID- 20805145
TI  - Emergency department visits for concussion in young child athletes.
AB  - OBJECTIVES: The objective of this study was to characterize emergency department
      (ED) visits for pediatric sport-related concussion (SRC) in pre-high school-
      versus high school-aged athletes. METHODS: A stratified probability sample of US
      hospitals that provide emergency services in the National Electronic Injury
      Surveillance System (1997-2007) and All Injury Program (2001-2005) was used.
      Concussion-related ED visits were analyzed for 8- to 13- and 14- to 19-year-old
      patients. Population data were obtained from the US Census Bureau; sport
      participation data were obtained from National Sporting Goods Association.
      RESULTS: From 2001 to 2005, US children who were aged 8 to 19 years had an
      estimated 502 000 ED visits for concussion. The 8- to 13-year-old group accounted
      for approximately 35% of these visits. Approximately half of all ED visits for
      concussion were SRC. The 8- to 13-year-old group sustained 40% of these, which
      represents 58% of all concussions in this group. Approximately 25% of all SRC
      visits in the 8- to 13-year-old group occurred during organized team sport (OTS).
      During the study period, approximately 4 in 1000 children aged 8 to 13 years and
      6 in 1000 children aged 14 to 19 years had an ED visit for SRC, and 1 in 1000
      children aged 8 to 13 years and 3 in 1000 children aged 14 to 19 years had an ED
      visit for concussion sustained during OTS. From 1997 to 2007, although
      participation had declined, ED visits for concussions in OTS in 8- to 13-year-old
      children had doubled and had increased by >200% in the 14- to 19-year-old group.
      CONCLUSIONS: The number of SRCs in young athletes is noteworthy. Additional
      research is required.

PMID- 20805146
TI  - Colonial pediatrics in the 1600s: governor John Winthrop the younger of
      Connecticut.

PMID- 20805150
TI  - American Academy of Pediatrics. Policy statement--sexuality, contraception, and
      the media.
AB  - From a health viewpoint, early sexual activity among US adolescents is a
      potential problem because of the risk of pregnancy and sexually transmitted
      infections. New evidence points to the media adolescents use frequently
      (television, music, movies, magazines, and the Internet) as important factors in
      the initiation of sexual intercourse. There is a major disconnect between what
      mainstream media portray-casual sex and sexuality with no consequences-and what
      children and teenagers need-straightforward information about human sexuality and
      the need for contraception when having sex. Television, film, music, and the
      Internet are all becoming increasingly sexually explicit, yet information on
      abstinence, sexual responsibility, and birth control remains rare. It is unwise
      to promote "abstinence-only" sex education when it has been shown to be
      ineffective and when the media have become such an important source of
      information about "nonabstinence." Recommendations are presented to help
      pediatricians address this important issue.

PMID- 20805147
TI  - Validation of the pediatric cardiac quality of life inventory.
AB  - OBJECTIVE: The purpose of this multicenter study was to confirm the validity and
      reliability of the Pediatric Cardiac Quality of Life Inventory (PCQLI). METHODS:
      Seven centers recruited pediatric patients (8-18 years of age) with heart disease
      (HD) and their parents to complete the PCQLI and generic health-related quality
      of life (Pediatric Quality of Life Inventory [PedsQL]) and non-quality of life
      (Self-Perception Profile for Children [SPPC]/Self-Perception Profile for
      Adolescents [SPPA] and Youth Self-Report [YSR]/Child Behavior Checklist [CBCL])
      tools. PCQLI construct validity was assessed through correlations of PCQLI scores
      between patients and parents and with severity of congenital HD, medical care
      utilization, and PedsQL, SPPC/SPPA, and YSR/CBCL scores. PCQLI test-retest
      reliability was evaluated. RESULTS: The study enrolled 1605 patient-parent pairs.
      Construct validity was substantiated by the association of lower PCQLI scores
      with Fontan palliation and increased numbers of cardiac operations, hospital
      admissions, and physician visits (P<.001); moderate to good correlations between
      patient and parent PCQLI scores (r=0.41-0.61; P<.001); and fair to good
      correlations between PCQLI total scores and PedsQL total (r=0.70-0.76), SPPC/SPPA
      global self-worth (r=0.43-0.46), YSR/CBCL total competency (r=0.28-0.37), and
      syndrome and Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition-oriented scale (r=-0.58 to -0.30; P<.001) scores. Test-retest reliability
      correlations were excellent (r=0.78-0.90; P<.001). CONCLUSIONS: PCQLI scores are
      valid and reliable for children and adolescents with congenital and acquired HD
      and may be useful for future research and clinical management.

PMID- 20805149
TI  - American Academy of Pediatrics. Policy statement--child fatality review.
AB  - Injury remains the leading cause of pediatric mortality and requires public
      health approaches to reduce preventable deaths. Child fatality review teams,
      first established to review suspicious child deaths involving abuse or neglect,
      have expanded toward a public health model of prevention of child fatality
      through systematic review of child deaths from birth through adolescence.
      Approximately half of all states report reviewing child deaths from all causes,
      and the process of fatality review has identified effective local and state
      prevention strategies for reducing child deaths. This expanded approach can be a
      powerful tool in understanding the epidemiology and preventability of child death
      locally, regionally, and nationally; improving accuracy of vital statistics data;
      and identifying public health and legislative strategies for reducing preventable
      child fatalities. The American Academy of Pediatrics supports the development of
      federal and state legislation to enhance the child fatality review process and
      recommends that pediatricians become involved in local and state child death
      reviews.

PMID- 20805151
TI  - American Academy of Pediatrics. Clinical report--gynecologic examination for
      adolescents in the pediatric office setting.
AB  - The American Academy of Pediatrics promotes the inclusion of the gynecologic
      examination in the primary care setting within the medical home. Gynecologic
      issues are commonly seen by clinicians who provide primary care to adolescents.
      Some of the most common concerns include questions related to pubertal
      development; menstrual disorders such as dysmenorrhea, amenorrhea,
      oligomenorrhea, and abnormal uterine bleeding; contraception; and sexually
      transmitted and non-sexually transmitted infections. The gynecologic examination
      is a key element in assessing pubertal status and documenting physical findings.
      Most adolescents do not need an internal examination involving a speculum or
      bimanual examination. However, for cases in which more extensive examination is
      needed, the primary care office with the primary care clinician who has
      established rapport and trust with the patient is often the best setting for
      pelvic examination. This report reviews the gynecologic examination, including
      indications for the pelvic examination in adolescents and the approach to this
      examination in the office setting. Indications for referral to a gynecologist are
      included. The pelvic examination may be successfully completed when conducted
      without pressure and approached as a normal part of routine young women's health
      care.

PMID- 20805152
TI  - American Academy of Pediatrics. Clinical report--sport-related concussion in
      children and adolescents.
AB  - Sport-related concussion is a "hot topic" in the media and in medicine. It is a
      common injury that is likely underreported by pediatric and adolescent athletes.
      Football has the highest incidence of concussion, but girls have higher
      concussion rates than boys do in similar sports. A clear understanding of the
      definition, signs, and symptoms of concussion is necessary to recognize it and
      rule out more severe intracranial injury. Concussion can cause symptoms that
      interfere with school, social and family relationships, and participation in
      sports. Recognition and education are paramount, because although proper
      equipment, sport technique, and adherence to rules of the sport may decrease the
      incidence or severity of concussions, nothing has been shown to prevent them.
      Appropriate management is essential for reducing the risk of long-term symptoms
      and complications. Cognitive and physical rest is the mainstay of management
      after diagnosis, and neuropsychological testing is a helpful tool in the
      management of concussion. Return to sport should be accomplished by using a
      progressive exercise program while evaluating for any return of signs or
      symptoms. This report serves as a basis for understanding the diagnosis and
      management of concussion in children and adolescent athletes.

PMID- 20805153
TI  - Is investigation of patients with haemoptysis and normal chest radiograph
      justified?

PMID- 20805154
TI  - Thrombolysis for postoperative pulmonary embolism: limiting the risk of
      haemorrhage.

PMID- 20805155
TI  - Pneumocystis jirovecii in pleural infection: a nucleic acid amplification study.

PMID- 20805156
TI  - Interleukin-5 inhibits glucocorticoid-mediated apoptosis in human eosinophils.

PMID- 20805157
TI  - Fatal haemoptysis caused by a ruptured Rasmussen's aneurysm.

PMID- 20805158
TI  - Maternal Nrf2 and gluthathione-S-transferase polymorphisms do not modify
      associations of prenatal tobacco smoke exposure with asthma and lung function in
      school-aged children.
AB  - BACKGROUND: Maternal smoking during pregnancy has detrimental effects on the
      respiratory health of infants and children. Polymorphisms of antioxidant genes
      including glutathione-S-transferases (GSTs) have been proposed as candidates for
      asthma and reduced lung function in children. METHODS: Women enrolled in the Avon
      Longitudinal Study of Parents and Children reported smoking habits during
      pregnancy. Asthma status in their children was established at age 7.5 years from
      parental reports and lung function was measured by spirometry at age 8.5 years.
      Maternal and child DNA were genotyped for deletions of GSTM1 and GSTT1 and
      functional polymorphisms of GSTP1 and Nrf2 genes. Associations of prenatal
      tobacco smoke exposure with asthma and lung function in children were stratified
      by maternal genotype. RESULTS: In 6606 children, maternal smoking during
      pregnancy was negatively associated with maximal mid expiratory flow (FEF(25-75))
      (-0.05 SD units, 95% CI -0.07 to -0.03, p<0.001). There was little evidence for
      interactions between maternal smoking and any maternal genotype considered on
      children's asthma or lung function. Maternal smoking was associated with reduced
      childhood FEF(25-75) only in mother-child pairs (n=1227) with both copies of
      GSTM1 deleted (-0.08 SD units, 95% CI -0.14 to -0.02, p=0.01) or (n=2313) at
      least one copy of GSTT1 present (-0.05 SD units, 95% CI -0.09 to 0, p=0.03).
      CONCLUSION: This study confirms a detrimental effect of intrauterine tobacco
      smoke exposure on childhood lung function but no strong evidence of modification
      by maternal genotype for important antioxidant genes. Adverse effects of fetal
      exposure to tobacco smoke on the respiratory health of children may be mediated
      by pathways other than oxidative stress.

PMID- 20805159
TI  - First independent replication study confirms the strong genetic association of
      ANXA11 with sarcoidosis.

PMID- 20805161
TI  - Diagnosing lung cancer earlier in the UK.

PMID- 20805163
TI  - The genetics of obstructive lung disease: big is beautiful.

PMID- 20805162
TI  - Asthma: improved understanding and insights into the challenges of achieving
      asthma control.

PMID- 20805164
TI  - Waking up to sleep-disordered breathing.

PMID- 20805165
TI  - Travelling in time with COPD.

PMID- 20805166
TI  - Non-invasive positive pressure ventilation in patients with stable hypercapnic
      COPD: light at the end of the tunnel?

PMID- 20805168
TI  - A 21-year-old male with right chest pain, dyspnoea on exertion and bloody pleural
      effusion.

PMID- 20805169
TI  - Impact of the seven-valent pneumococcal conjugate vaccination (PCV7) programme on
      childhood hospital admissions for bacterial pneumonia and empyema in England:
      national time-trends study, 1997-2008.
AB  - BACKGROUND: Childhood bacterial pneumonia and empyema rates have reportedly
      increased in recent years in Europe. In September 2006 the seven-valent
      pneumococcal conjugate vaccination (PCV7) was introduced to the childhood
      national immunisation programme in England following a successful PCV7 campaign
      in the USA. The aim of this study was to report national time trends in hospital
      admissions for childhood bacterial pneumonia and empyema in England before and
      after the introduction of PCV7. METHODS: A population-based time-trend analysis
      of Hospital Episode Statistics data of children aged <15 years admitted to all
      NHS hospitals in England, with a primary diagnosis of bacterial pneumonia and
      empyema from 1997 to 2008 was performed. Annual crude and age-sex standardised
      hospital admission rates for bacterial pneumonia and empyema were calculated.
      RESULTS: Admission rates for bacterial pneumonia and empyema increased from 1997
      to 2006, then declined to 2008. Bacterial pneumonia rates decreased to 1079 (95%
      CI 1059 to 1099) per million children and empyema rates decreased to 14 (95% CI
      11 to 16) per million children. The RR for bacterial pneumonia admissions was
      1.19 (95% CI 1.16 to 1.22) in 2006 compared with 2004 and 0.81 (95% CI 0.79 to
      0.83) in 2008 compared with 2006. For empyema, the corresponding RRs were 1.77
      (95% CI 1.38 to 2.28) in 2006 compared with 2004 and 0.78 (95% CI 0.62 to 0.98)
      in 2008 compared with 2006. CONCLUSION: Childhood bacterial pneumonia and empyema
      admission rates were increasing prior to 2006 and decreased by 19% and 22%
      respectively between 2006 and 2008, following the introduction of the PCV7
      pneumococcal conjugate vaccination to the national childhood immunisation
      programme.

PMID- 20805170
TI  - Quantitative analysis of high-resolution computed tomography scans in severe
      asthma subphenotypes.
AB  - BACKGROUND: Severe asthma is a heterogeneous condition. Airway remodelling is a
      feature of severe asthma and can be determined by the assessment of high
      resolution computed tomography (HRCT) scans. The aim of this study was to assess
      whether airway remodelling is restricted to specific subphenotypes of severe
      asthma. METHODS: A retrospective analysis was performed of HRCT scans from
      subjects who had attended a single-centre severe asthma clinic between 2003 and
      2008. The right upper lobe apical segmental bronchus (RB1) dimensions were
      measured and the clinical and sputum inflammatory characteristics associated with
      RB1 geometry were assessed by univariate and multivariate regression analyses.
      Longitudinal sputum data were available and were described as area under the time
      curve (AUC). Comparisons were made in RB1 geometry across subjects in four
      subphenotypes determined by cluster analysis, smokers and non-smokers, and
      subjects with and without persistent airflow obstruction. RESULTS: Ninety-nine
      subjects with severe asthma and 16 healthy controls were recruited. In the
      subjects with severe asthma the RB1 percentage wall area (%WA) was increased
      (p=0.009) and lumen area (LA)/body surface area (BSA) was decreased (p=0.008)
      compared with controls but was not different across the four subphenotypes.
      Airway geometry was not different between smokers and non-smokers and RB1 %WA was
      increased in those with persistent airflow obstruction. RB1 %WA in severe asthma
      was best associated with airflow limitation and persistent neutrophilic airway
      inflammation (model R(2)=0.27, p=0.001). CONCLUSIONS: Airway remodelling of
      proximal airways occurs in severe asthma and is associated with impaired lung
      function and neutrophilic airway inflammation.

PMID- 20805171
TI  - Increased levels of osteopontin in sputum supernatant in severe refractory
      asthma.
AB  - BACKGROUND: Osteopontin (OPN) is a glycoprotein that has been associated with
      inflammation and fibrosis. Severe refractory asthma (SRA) is characterised by an
      intense inflammatory and remodelling process. The aim of this study was to
      investigate the levels of OPN in sputum supernatants of patients with SRA, to
      compare them with milder forms of the disease and to investigate their possible
      association with mediators and cells involved in the inflammatory and remodelling
      process. METHODS: 33 patients with SRA, 29 with moderate asthma, 21 with steroid
      naive asthma and 20 healthy subjects were studied. All subjects underwent lung
      function tests, bronchial hyper-responsiveness assessment and sputum induction
      for cell count identification and measurement of OPN, vascular endothelial growth
      factor, transforming growth factor beta1 (TGF-beta1), cysteinyl leukotrienes,
      interleukin 13 (IL-13), eosinophilic cationic protein (ECP) and IL-8 in sputum
      supernatants. RESULTS: Median (IQR) OPN levels (pg/ml) were significantly higher
      in patients with SRA than in those with moderate asthma, steroid-naive asthma and
      healthy control subjects (1840 (1125-11000) vs 130 (100-210) vs 100 (67-130) vs
      50 (42-70), respectively, p<0.001). Regression analysis showed a significant
      association between log OPN and sputum eosinophils, cysteinyl leukotrienes, IL
      13, TGF-beta1 and ECP. TGF-beta1 represented the strongest association with OPN.
      The above associations were not observed in milder forms of the disease or in
      healthy subjects. CONCLUSIONS: The results indicate that OPN levels are higher in
      SRA than in less severe forms of the disease. Moreover, OPN is associated with
      mediators involved in both the inflammatory and remodelling process such as TGF
      beta1, IL-13 and cysteinyl leukotrienes only in SRA.

PMID- 20805172
TI  - Refractory asthma in the UK: cross-sectional findings from a UK multicentre
      registry.
AB  - INTRODUCTION: Refractory asthma represents a significant unmet clinical need
      where the evidence base for the assessment and therapeutic management is limited.
      The British Thoracic Society (BTS) Difficult Asthma Network has established an
      online National Registry to standardise specialist UK difficult asthma services
      and to facilitate research into the assessment and clinical management of
      difficult asthma. METHODS: Data from 382 well characterised patients, who
      fulfilled the American Thoracic Society definition for refractory asthma
      attending four specialist UK centres--Royal Brompton Hospital, London, Glenfield
      Hospital, Leicester, University Hospital of South Manchester and Belfast City
      Hospital--were used to compare patient demographics, disease characteristics and
      healthcare utilisation. RESULTS: Many demographic variables including gender,
      ethnicity and smoking prevalence were similar in UK centres and consistent with
      other published cohorts of refractory asthma. However, multiple demographic
      factors such as employment, family history, atopy prevalence, lung function,
      rates of hospital admission/unscheduled healthcare visits and medication usage
      were different from published data and significantly different between UK
      centres. General linear modelling with unscheduled healthcare visits, rescue oral
      steroids and hospital admissions as dependent variables all identified a
      significant association with clinical centre; different associations were
      identified when centre was not included as a factor. CONCLUSION: Whilst there are
      similarities in UK patients with refractory asthma consistent with other
      comparable published cohorts, there are also differences, which may reflect
      different patient populations. These differences in important population
      characteristics were also identified within different UK specialist centres.
      Pooling multicentre data on subjects with refractory asthma may miss important
      differences and potentially confound attempts to phenotype this population.

PMID- 20805175
TI  - Prediction of asthma in symptomatic preschool children using exhaled nitric
      oxide, Rint and specific IgE.
AB  - RATIONALE: For clinicians it remains very difficult to predict whether preschool
      children with symptoms suggestive of asthma will develop asthma in later
      childhood. OBJECTIVE: To investigate whether measurement of fraction of exhaled
      nitric oxide (FE(NO)), interrupter resistance (Rint) or specific immunoglobulin E
      (IgE) in 4-year-old children with suggestive symptoms can predict asthma symptoms
      up to age 8 years. METHODS: Children were recruited from the PIAMA birth cohort.
      All children with symptoms suggestive of asthma at age 3 or 4 years, who were
      invited for medical examination at age 4 (n=848), were eligible. Associations of
      FE(NO) (n=308), Rint (n=482) and specific IgE (n=380) at 4 years with wheezing
      and asthma at the ages of 5-8 years were assessed using repeated measurement
      analyses. The added predictive value of these objective tests was then
      investigated by including parameters for clinical history in the model. RESULTS:
      FE(NO) and specific IgE measured at 4 years were associated with wheezing and
      asthma at 8 years. Both tests also remained significant predictors after mutual
      adjustment and adjustment for clinical history: OR on wheezing at 8 years for
      FE(NO) ((10)log-scale, per IQR) 1.6 (95% CI 1.1 to 2.2) and for specific IgE 2.8
      (95% CI 1.9 to 4.1). Rint was significantly associated with wheezing at age 6,
      but not at 7 and 8 years. CONCLUSIONS: In preschool children with symptoms
      suggestive of asthma, both FE(NO) and specific IgE measured at age 4, but not
      Rint, improved the prediction of asthma symptoms until the age of 8 years,
      independent of clinical history.

PMID- 20805173
TI  - Bronchial reactivity indices are determinants of health-related quality of life
      in patients with stable asthma.
AB  - BACKGROUND: A very weak relationship has been reported between the health-related
      quality of life (HRQL) of patients with asthma and their degree of airway hyper
      responsiveness (AHR), evaluated in terms of sensitivity. However, this
      relationship still has not been sufficiently explored for bronchial reactivity
      indices. OBJECTIVES: To analyse the relationship between bronchial reactivity and
      sensitivity with the HRQL of patients with stable asthma, identifying the
      functional parameters that determine HRQL. METHODS: In 103 consecutive patients
      with stable asthma, HRQL was evaluated using the Asthma Quality of Life
      Questionnaire (AQLQ). Patients underwent spirometry and non-specific bronchial
      provocation with methacoline. Sensitivity (PD(20)) and reactivity (dose-response
      slope (DRS), continuous index of responsiveness (CIR) and bronchial reactivity
      index (BRI)) of the dose-response curve were analysed. RESULTS: BRI presented
      significant differences with different degrees of asthma severity. Although
      patients with AHR showed poorer quality of life than patients without AHR, the
      AQLQ total score was not related to PD(20) but rather to DRS (r=-0.784), CIR (r=
      0.712) and BRI (r=-0.776). The indices of bronchial reactivity reached a negative
      correlation with all the domains of the AQLQ. In a multiple linear regression
      model, BRI, DRS, FIV(1) (forced inspiratory volume in 1 s) and VCIN (inspiratory
      vital capacity) were identified as independent predictors of the AQLQ total score
      (r(2)=0.742, p<0.001). CONCLUSION: In patients with stable asthma, bronchial
      reactivity is associated with HRQL. This could justify incorporating bronchial
      reactivity indices in bronchial provocation analyses.

PMID- 20805177
TI  - Breathing pattern and chest wall volumes during exercise in patients with cystic
      fibrosis, pulmonary fibrosis and COPD before and after lung transplantation.
AB  - BACKGROUND: Pulmonary fibrosis (PF), cystic fibrosis (CF) and chronic obstructive
      pulmonary disease (COPD) often cause chronic respiratory failure (CRF). METHODS:
      In order to investigate if there are different patterns of adaptation of the
      ventilatory pump in CRF, in three groups of lung transplant candidates with PF
      (n=9, forced expiratory volume in 1 s (FEV(1))=37+/-3% predicted, forced vital
      capacity (FVC)=32+/-2% predicted), CF (n=9, FEV(1)=22+/-3% predicted, FVC=30+/-3%
      predicted) and COPD (n=21, FEV(1)=21+/-1% predicted, FVC=46+/-2% predicted), 10
      healthy controls and 16 transplanted patients, total and compartmental chest wall
      volumes were measured by opto-electronic plethysmography during rest and
      exercise. RESULTS: Three different breathing patterns were found during CRF in
      PF, CF and COPD. Patients with COPD were characterised by a reduced duty cycle at
      rest and maximal exercise (34+/-1%, p<0.001), while patients with PF and CF
      showed an increased breathing frequency (49+/-6 and 34+/-2/min, respectively) and
      decreased tidal volume (0.75+/-0.10 and 0.79+/-0.07 litres) (p<0.05). During
      exercise, end-expiratory chest wall and rib cage volumes increased significantly
      in patients with COPD and CF but not in those with PF. End-inspiratory volumes
      did not increase in CF and PF. The breathing pattern of transplanted patients was
      similar to that of healthy controls. CONCLUSIONS: There are three distinct
      patterns of CRF in patients with PF, CF and COPD adopted by the ventilatory pump
      to cope with the underlying lung disease that may explain why patients with PF
      and CF are prone to respiratory failure earlier than patients with COPD. After
      lung transplantation the chronic adaptations of the ventilatory pattern to
      advanced lung diseases are reversible and indicate that the main contributing
      factor is the lung itself rather than systemic effects of the disease.

PMID- 20805178
TI  - Postoperative pulmonary complications following thoracic surgery: are there any
      modifiable risk factors?
AB  - BACKGROUND: Postoperative pulmonary complications (PPC) are the most frequently
      observed complications following lung resection, of which pneumonia and
      atelectasis are the most common. PPCs have a significant clinical and economic
      impact associated with increased observed number of deaths, morbidity, length of
      stay and associated cost. The aim of this study was to assess the incidence and
      impact of PPCs and to identify potentially modifiable independent risk factors.
      METHODS: A prospective observational study was carried out on all patients
      following lung resection via thoracotomy in a regional thoracic centre over 13
      months. PPC was assessed using a scoring system based on chest x-ray, raised
      white cell count, fever, microbiology, purulent sputum and oxygen saturations.
      RESULTS: Thirty-four of 234 subjects (14.5%) had clinical evidence of PPC. The
      PPC patient group had a significantly longer length of stay (LOS) in hospital,
      high dependency unit (HDU) LOS, higher frequency of intensive care unit (ITU)
      admission and a higher number of hospital deaths. Older patients, body mass index
      (BMI) > or =30 kg/m(2), preoperative activity <400 m, American Society of
      Anesthesiologists (ASA) score > or =3, smoking history, chronic obstructive
      pulmonary disease (COPD), lower preoperative forced expiratory volume in 1 s
      (FEV(1)) and predicted postoperative (PPO) FEV(1) were all significantly (p<0.05)
      associated with PPC on univariate analysis. Multivariate analysis confirmed that
      age >75 years, BMI > or =30 kg/m(2), ASA > or =3, smoking history and COPD were
      significant independent risk factors in the development of PPC (p<0.05).
      CONCLUSION: The clinical impact of PPCs is marked. Significant independent
      preoperative risk factors have been identified in current clinical practice.
      Potentially modifiable risk factors include BMI, smoking status and COPD. The
      impact of targeted therapy requires further evaluation.

PMID- 20805179
TI  - Validation of a parent-proxy quality of life questionnaire for paediatric chronic
      cough (PC-QOL).
AB  - BACKGROUND: Quality of life (QOL) measures are an important patient-relevant
      outcome measure for clinical studies. Currently there is no fully validated cough
      specific QOL measure for paediatrics. The objective of this study was to validate
      a cough-specific QOL questionnaire for paediatric use. METHOD: 43 children (28
      males, 15 females; median age 29 months, IQR 20-41 months) newly referred for
      chronic cough participated. One parent of each child completed the 27-item Parent
      Cough-Specific QOL questionnaire (PC-QOL), and the generic child (Pediatric QOL
      Inventory 4.0 (PedsQL)) and parent QOL questionnaires (SF-12) and two cough
      related measures (visual analogue score and verbal category descriptive score) on
      two occasions separated by 2-3 weeks. Cough counts were also objectively measured
      on both occasions. RESULTS: Internal consistency for both the domains and total
      PC-QOL at both test times was excellent (Cronbach alpha range 0.70-0.97).
      Evidence for repeatability and criterion validity was established, with
      significant correlations over time and significant relationships with the cough
      measures. The PC-QOL was sensitive to change across the test times and these
      changes were significantly related to changes in cough measures (PC-QOL with:
      verbal category descriptive score, r(s)=-0.37, p=0.016; visual analogue score,
      r(s)=-0.47, p=0.003). Significant correlations of the difference scores for the
      social domain of the PC-QOL and the domain and total scores of the PedsQL were
      also noted (r(s)=0.46, p=0.034). CONCLUSION: The PC-QOL is a reliable and valid
      outcome measure that assesses QOL related to childhood cough at a given time
      point and measures changes in cough-specific QOL over time.

PMID- 20805181
TI  - The effects of sleeping position on ventilatory responses to carbon dioxide in
      premature infants.
AB  - BACKGROUND: The prone sleeping position, particularly in prematurely born
      infants, is associated with an increased risk of sudden infant death syndrome. A
      possible mechanism is an impaired ability to respond to respiratory compromise.
      The hypothesis that the ventilatory response to a carbon dioxide (CO(2))
      challenge in convalescent, prematurely born infants would be lower in the prone
      compared with the supine position was therefore tested. METHODS: In each
      position, ventilatory responses to increasing levels of inspired CO(2) were
      assessed. The airway pressure change after the first 100 ms of an occluded
      inspiration (P(0.1)) and the maximum inspiratory pressure with an occluded airway
      during crying (P(imax)) were measured; the ratio of the P(0.1) to the P(imax) at
      each inspired CO(2) level and the slope of the P(0.1)/P(imax) response were
      calculated. Chest and abdominal wall asynchrony was assessed using inductance
      plethysmography and functional residual capacity (FRC) measured using a helium
      gas dilution technique. RESULTS: Eighteen infants with a median postmenstrual age
      of 35 (range 35-37) weeks were studied. In the prone versus the supine position,
      the mean P(0.1) (p=0.002), the mean P(imax) (p=0.006), the increase in P(0.1)
      with increasing CO(2) (p=0.007) and the P(0.1)/P(imax) response slope (p=0.007)
      were smaller. Thoracoabdominal asynchrony was not significantly influenced by
      position or inspired CO(2). FRC was higher in the prone position (p=0.019).
      CONCLUSIONS: Convalescent, prematurely born infants have a reduced ventilatory
      response to CO(2) challenge in the prone position, suggesting they may have an
      impaired ability to respond to respiratory compromise in that position.

PMID- 20805182
TI  - Predictors of long-term compliance with continuous positive airway pressure.
AB  - BACKGROUND: There are very few data on objectively assessed long-term compliance
      with continuous positive airway pressure (CPAP). No single factor has been
      consistently identified as predictive of continued CPAP use. METHODS: Adherence
      to and associations with objective CPAP use were examined in 639 of 3900 patients
      in whom CPAP treatment was started between 1994 and 2005. Kaplan-Meier survival
      analyses were used to estimate the proportion of patients still on CPAP. Cox
      regression models were used to explore the effects of covariates on continued use
      of CPAP. RESULTS: The median (IQR) follow-up time after initiating CPAP therapy
      was 3.9 (1.5-6.9) years and the average use of CPAP was 6.2 (4.5-7.3) h/night.
      The percentage of patients adherent to CPAP after 5 and 10 years was 81% and 70%,
      respectively. Multivariate analysis, including gender, age, neck circumference,
      Epworth Sleepiness Score, oxygen desaturation index (ODI) and research study
      participation, indicated that ODI was the only clinical variable independently
      associated with long-term adherence to CPAP (HR per 1 event=0.97, p<0.001, 95% CI
      0.96 to 0.98). ODI categories were significantly associated with the risk for
      stopping CPAP in multivariate analysis (using ODI group 0-15/h as reference, HR
      for ODI group >15-30/h=0.68, p=0.100, 95% CI 0.43 to 1.08; for ODI group >30
      60/h=0.37, p<0.001, 95% CI 0.22 to 0.60; and for ODI group >60/h=0.17, p=0.001,
      95% CI 0.06 to 0.48). CONCLUSIONS: The majority of patients with sleep-disordered
      breathing are using CPAP in the long term and the severity of sleep-disordered
      breathing rather than sleepiness determines long-term adherence to CPAP therapy.

PMID- 20805183
TI  - Diagnosis of pulmonary Langerhans cell histiocytosis by CT-guided core biopsy of
      lung: a report of three cases.
AB  - A pathological diagnosis of pulmonary Langerhans cell histiocytosis (PLCH)
      usually requires a surgical lung biopsy. To date, diagnosis of PLCH by core
      needle biopsy has not been reported. Three cases are presented of PLCH diagnosed
      by CT-guided core biopsy in adult female smokers found to have multiple small
      bilateral lung nodules. The nodules biopsied were 5 mm, 7 mm and 1 cm in size,
      and showed interstitial expansion by Langerhans cells and eosinophils. CT-guided
      core biopsy should be considered as one of the less invasive techniques by which
      a pathological diagnosis of PLCH can be established.

PMID- 20805184
TI  - Treatment of COPD: the sooner the better?
AB  - Classical belief is that only smoking cessation, and not pharmacotherapy,
      beneficially affect disease progression in chronic obstructive pulmonary disease
      (COPD). In recent years, new data on pharmacotherapy of COPD became available
      that shed new light on this question. The present paper reviews these data
      critically in an attempt to put them in a proper perspective. The most impressive
      new data are subgroup analyses of two large-scale long-term trials. With these
      new data it is now clear that patients in GOLD (Global Initiative for Chronic
      Obstructive Pulmonary Disease) stage II benefit as much from pharmacotherapy as
      patients in the later stages of the disease. Effects on prebronchodilator and
      postbronchodilator forced expiratory volume in 1 s (FEV(1)), health-related
      quality of life, exacerbations and hospitalisations appear at least as pronounced
      in GOLD stage II as in the other GOLD stages. In addition, evidence suggestive of
      an effect on disease progression is available in the sense of an effect on rate
      of decline of FEV(1), and trends for reductions in mortality. Finally, good
      evidence is available that, in contrast to conventional thinking, decline of
      FEV(1) occurs at a considerably faster rate in the early stages of the disease.
      These data together with the high prevalence of co-morbidities from early in the
      disease onwards provide us with strong suggestive evidence for early intensive
      intervention in COPD. New trials, particularly demonstrating the detrimental
      effects of delaying treatment until later in the course of the disease, are
      required to render the evidence for early intensive intervention irrefutable.

PMID- 20805186
TI  - Bronchoalveolar lavage immunodiagnosis for tuberculosis suspects in Europe and
      Africa.

PMID- 20805187
TI  - Exercise-induced bronchoconstriction and exercise testing in an international
      rugby union team.

PMID- 20805188
TI  - Comparative proteomics uncovers the signature of natural selection acting on the
      ejaculate proteomes of two cricket species isolated by postmating, prezygotic
      phenotypes.
AB  - Two of the most well-supported patterns to have emerged over the past two decades
      of research in evolutionary biology are the occurrence of divergent natural
      selection acting on many male and female reproductive tract proteins and the
      importance of postmating, prezygotic phenotypes in reproductively isolating
      closely related species. Although these patterns appear to be common across a
      wide variety of taxa, the link between them remains poorly documented. Here, we
      utilize comparative proteomic techniques to determine whether or not there is
      evidence for natural selection acting on the ejaculate proteomes of two cricket
      species (Allonemobius fasciatus and A. socius) which are reproductively isolated
      primarily by postmating, prezygotic phenotypes. In addressing this question, we
      compare the degree of within-species polymorphism and between-species divergence
      between the ejaculate and thorax proteomes of these two species. We found that
      the ejaculate proteomes are both less polymorphic and more divergent than the
      thorax proteomes. Additionally, we assessed patterns of nucleotide variation for
      two species-specific ejaculate proteins and found evidence for both reduced
      levels of variation within species and positive selection driving divergence
      between species. In contrast, non-species-specific proteins exhibited higher
      levels of within-species nucleotide variation and no signatures of positive
      selection. Nucleotide and putative functional data for the two species-specific
      proteins, along with data for a third protein (ejaculate serine protease),
      suggest that all three of these genes are candidate speciation genes in need of
      further study. Overall, these patterns of proteome and nucleotide divergence
      provide support for the hypothesis that there is a causative link between
      selection-driven divergence of male ejaculate proteins and the evolution of
      postmating, prezygotic barriers to gene flow within Allonemobius.

PMID- 20805189
TI  - MicroRNA networks alter to conform to transcription factor networks adding
      redundancy and reducing the repertoire of target genes for coordinated
      regulation.
AB  - Transcription factors (TFs) and microRNAs (miRNAs) comprise two major layers of
      gene regulatory networks (GRNs). TFs and miRNAs function coordinately, but they
      have distinct molecular mechanisms and evolutionary backgrounds. Therefore, we
      aimed to systematically reveal the difference in contribution between TF and
      miRNA networks to the evolution of their coordinated regulations by focusing on
      composite feedforward circuits (cFFCs) that each comprises a TF and an miRNA. We
      compiled 124,736 human-mouse conserved TF regulatory connections and 34,298
      conserved miRNA regulatory connections into two distinct connection matrices. To
      differentially assess the contributions to cFFC formation of TFs and miRNAs, we
      randomized one matrix and kept the other unchanged and subsequently examined the
      number of cFFCs, the number of cFFC-targeted genes, and the redundancy formed by
      cFFCs in comparison with those of the real GRNs. Because the matrices represent
      selectively constrained networks, if selection has been operating on the networks
      for or against cFFC formation, the values of cFFC network properties would
      deviate significantly from the expectation of the randomized networks. As the
      cFFC includes both TF and miRNA connections, the partial randomizations indicate
      the extent of influence of selection on cFFC formation differentially between TF
      and miRNA networks. Thus, we adopted the deviation of each cFFC network property
      value as a measure to estimate the extent of influence of selection on cFFCs and
      to compare the contribution between TF and miRNA networks. We found that miRNA
      regulatory networks changed their configuration such that they conformed to the
      stable TF regulatory networks with an increased circuit redundancy and a marked
      reduction in the repertoire of cFFC-targeted genes. We also revealed that this
      redundancy-adding role is preferentially attributable to miRNA network
      alterations. The results indicate that the redundancy-adding role might serve as
      a niche for many miRNA connections to survive, avoiding conflicts with the stable
      TF regulatory networks.

PMID- 20805190
TI  - Extreme reconfiguration of plastid genomes in the angiosperm family Geraniaceae:
      rearrangements, repeats, and codon usage.
AB  - Geraniaceae plastid genomes (plastomes) have experienced a remarkable number of
      genomic changes. The plastomes of Erodium texanum, Geranium palmatum, and
      Monsonia speciosa were sequenced and compared with other rosids and the
      previously published Pelargonium hortorum plastome. Geraniaceae plastomes were
      found to be highly variable in size, gene content and order, repetitive DNA, and
      codon usage. Several unique plastome rearrangements include the disruption of two
      highly conserved operons (S10 and rps2-atpA), and the inverted repeat (IR) region
      in M. speciosa does not contain all genes in the ribosomal RNA operon. The
      sequence of M. speciosa is unusually small (128,787 bp); among angiosperm
      plastomes sequenced to date, only those of nonphotosynthetic species and those
      that have lost one IR copy are smaller. In contrast, the plastome of P. hortorum
      is the largest, at 217,942 bp. These genomes have experienced numerous gene and
      intron losses and partial and complete gene duplications. Some of the losses are
      shared throughout the family (e.g., trnT-GGU and the introns of rps16 and rpl16);
      however, other losses are homoplasious (e.g., trnG-UCC intron in G. palmatum and
      M. speciosa). IR length is also highly variable. The IR in P. hortorum was
      previously shown to be greatly expanded to 76 kb, and the IR is lost in E.
      texanum and reduced in G. palmatum (11 kb) and M. speciosa (7 kb). Geraniaceae
      plastomes contain a high frequency of large repeats (>100 bp) relative to other
      rosids. Within each plastome, repeats are often located at rearrangement end
      points and many repeats shared among the four Geraniaceae flank rearrangement end
      points. GC content is elevated in the genomes and also in coding regions relative
      to other rosids. Codon usage per amino acid and GC content at third position
      sites are significantly different for Geraniaceae protein-coding sequences
      relative to other rosids. Our findings suggest that relaxed selection and/or
      mutational biases lead to increased GC content, and this in turn altered codon
      usage. We propose that increases in genomic rearrangements, repetitive DNA,
      nucleotide substitutions, and GC content may be caused by relaxed selection
      resulting from improper DNA repair.

PMID- 20805191
TI  - A universal molecular clock of protein folds and its power in tracing the early
      history of aerobic metabolism and planet oxygenation.
AB  - The standard molecular clock describes a constant rate of molecular evolution and
      provides a powerful framework for evolutionary timescales. Here, we describe the
      existence and implications of a molecular clock of folds, a universal recurrence
      in the discovery of new structures in the world of proteins. Using a phylogenomic
      structural census in hundreds of proteomes, we build phylogenies and time lines
      of domains at fold and fold superfamily levels of structural complexity. These
      time lines correlate approximately linearly with geological timescales and were
      here used to date two crucial events in life history, planet oxygenation and
      organism diversification. We first dissected the structures and functions of
      enzymes in simulated metabolic networks. The placement of anaerobic and aerobic
      enzymes in the time line revealed that aerobic metabolism emerged about 2.9
      billion years (giga-annum; Ga) ago and expanded during a period of about 400 My,
      reaching what is known as the Great Oxidation Event. During this period, enzymes
      recruited old and new folds for oxygen-mediated enzymatic activities. Remarkably,
      the first fold lost by a superkingdom disappeared in Archaea 2.6 Ga ago, within
      the span of oxygen rise, suggesting that oxygen also triggered diversification of
      life. The implications of a molecular clock of folds are many and important for
      the neutral theory of molecular evolution and for understanding the growth and
      diversity of the protein world. The clock also extends the standard concept that
      was specific to molecules and their timescales and turns it into a universal
      timescale-generating tool.

PMID- 20805192
TI  - The effect of re-employment on perceived health.
AB  - BACKGROUND: The relationship between unemployment and poor health has been well
      established. Unemployment causes poor health, and poor health increases the
      probability of unemployment. METHODS: A prospective study with 6&emsp14;months'
      follow-up was conducted among unemployed participants receiving social security
      benefits who were capable of full-time employment and were referred to a re
      employment training centre. Re-employment was defined as ending social security
      benefits for at least 3 months because of starting with paid employment. Health
      related quality of life was measured by the 36-Item Short-Form Health Survey. A
      Cox proportional hazards analysis was used to determine the factors that
      predicted re-employment during follow-up. The influence of re-employment on
      changes in perceived health was investigated with linear regression analysis.
      RESULTS: Unemployed participants with a poor health at baseline were less likely
      to return to paid employment during follow-up. Almost all dimensions of health at
      baseline had an influence on the likelihood of becoming employed. Among the re
      employed participants, general health, physical functioning, social functioning,
      vitality, mental health, bodily pain and role limitations due to emotional or
      physical problems improved, with an effect size varying from 0.11 to 0.66.
      CONCLUSIONS: This study provides evidence that re-employment leads to improvement
      of self-perceived health within a short time window. This suggests that labour
      force participation should be considered as therapeutic intervention within
      health promotion programmes among unemployed persons.

PMID- 20805193
TI  - Reduced probability of smoking cessation in men with increasing number of job
      losses and partnership breakdowns.
AB  - BACKGROUND: Unemployment and partnership breakdowns are common stressful life
      events, but their association with smoking cessation has been investigated in
      only a few studies. OBJECTIVE: To investigate how history of employment and
      cohabitation affects the probability of smoking cessation and to study joint
      exposure to both. METHODS: Birth cohort study of smoking cessation of 6232 Danish
      men born in 1953 with a follow-up at age 51 (response rate 66.2%). History of
      unemployment and cohabitation was measured annually using register data.
      Information on smoking cessation was obtained by a questionnaire. RESULTS: The
      probability of smoking cessation decreased with the number of job losses (ranging
      from 1 OR 0.54 (95% CI 0.46 to 0.64) to 3+ OR 0.41 (95% CI 0.30 to 0.55)) and of
      broken partnerships (ranging from 1 OR 0.74 (95% CI 0.63 to 0.85) to 3+ OR 0.50
      (95% CI 0.39 to 0.63)). Furthermore, smoking cessation was associated with the
      duration of the periods of unemployment (ranging from 1-5 years (OR 0.75, 95% CI
      0.65 to 0.85) to 10-23 years (OR 0.29, 95% CI 0.22 to 0.38)) and with living
      without a partner for > 5 years (ranging from 6-9 years to 10-23 years (OR 0.80,
      95% CI 0.66 to 0.97) to 10-23 years (OR 0.44, 95% CI 0.37 to 0.52)). Those who
      never cohabited and experienced one or more job losses had a particular low
      chance of smoking cessation (OR 0.19, 95% CI 0.12 to 0.30). CONCLUSION: The
      numbers of job losses and of broken partnerships were both inversely associated
      with probability of smoking cessation.

PMID- 20805194
TI  - Geographical variation in infant mortality, stillbirth and low birth weight in
      Northern Ireland, 1992-2002.
AB  - BACKGROUND: Improving the health of expectant mothers and reductions in health
      inequalities, are repeatedly prioritised in policy reports in England and
      Northern Ireland. Measurement of underlying rates, and geographical variation in
      rates, of adverse birth outcomes are tools in monitoring these priorities.
      METHODS: Northern Ireland data on stillbirths, infant mortality and low birth
      weight (1992-2002) were linked to board (n=4), district council (n=26) and 1991
      census wards (n=568). Underlying variations in rates were estimated at each
      geographical level, unadjusted and controlling for year, ward-level deprivation,
      settlement size and higher geographical levels. Impacts on geographical variation
      of individual social class, maternal age, multiple birth and smoking were
      assessed. RESULTS: There was significant variation in underlying rates of low
      birth weight (<2500 g) at all three geographical levels. Controlling for smoking
      reduced variation between wards. Geographical variation proved more robust for
      medium than for very low birth weight. No variation was seen between boards for
      other outcomes, nor between district level rates of infant mortality. Evidence
      was weak for variation in district rates of neonatal deaths and stillbirths, and
      variation in ward-level adjusted stillbirth rates was not significant. Variation
      in ward-level infant death rates was robust to all adjustments, with risks
      tripling (infant mortality) or quadrupling (neonatal mortality) between the 10th
      and 90th percentile. CONCLUSIONS: Strong evidence was found of geographical
      variation in infant mortality and low birth weight, unexplained by individual
      risk factors or by area-level deprivation. Geographical targeting or area-level
      interventions might look beyond deprivation scores, to other environmental and
      social factors.

PMID- 20805196
TI  - Producers, communicators and consumers of 'risk'.

PMID- 20805195
TI  - Sources of greater fetal vulnerability to airborne polycyclic aromatic
      hydrocarbons among African Americans.
AB  - BACKGROUND: This study attempted to clarify the household and mother's lifestyle
      factors that contribute to the greater fetal vulnerability of African-American
      individuals to airborne polycyclic aromatic hydrocarbons (PAH). METHODS: Non
      smoking pregnant women with no known risks of adverse birth outcome were
      monitored for their personal exposure to airborne PAH. Birth outcomes were
      collected from the hospital medical record. Modification of the airborne PAH
      effects was statistically examined. In linear regression analyses, modification
      of PAH effect by demographic, socioeconomic and behavioural traits on birth
      weight and fetal growth ratio were respectively tested, adjusting for the
      gestational age, gender, parity, delivery season, maternal body mass index and
      weight gained during the present pregnancy. RESULTS: Maternal obesity exacerbated
      the airborne PAH risk by -491 g per 25th to 80th percentile unit exposure (95% CI
      -197 to -786 g; p<0.01) among African Americans. In addition, frequent dietary
      intake of smoked, grilled or barbequed items independently reduced the birth
      weight of African-American newborns by -204 g (95% CI -21 to -387 g; p=0.03).
      CONCLUSION: Maternal obesity significantly exacerbated the risk of prenatal PAH
      exposure in African-American newborns. Also, frequent dietary consumption of PAH
      laden food items posed an independent risk on the reduced birth weight among
      African Americans.

PMID- 20805197
TI  - Height loss and future coronary heart disease in London: the Whitehall II study.
AB  - BACKGROUND: Although several plausible biological mechanisms have been advanced
      for the association between greater physical stature and lower coronary heart
      disease (CHD) risk in prospective cohort studies, the importance of one of the
      principal artefactual explanations--reverse causality due to shrinkage--remains
      unresolved. To explore this issue, studies with repeat measurements of height are
      required, but, to date, such data have been lacking. OBJECTIVE: To examine the
      possible relationship between height loss and future CHD. METHODS: Data were
      analysed from the Whitehall II prospective cohort study of 3802 men and 1615
      women who participated in a physical examination in 1985-8, had their height re
      measured in 1997-9, and were then followed up for fatal and non-fatal CHD.
      RESULTS: A mean follow-up of 7.4 years after the second height measurement gave
      rise to 69 CHD events in men and 18 in women. After adjustment for baseline CHD
      risk factors, greater loss of physical stature between survey and resurvey was
      associated with an increased risk of CHD in men (HR; 95% CI for a one SD
      increase: 1.24; 1.00 to 1.53) but not women (0.93; 0.58 to 1.50). CONCLUSIONS:
      Reverse causality due to shrinkage may contribute to the inverse association
      between a single measurement of height and later CHD in other studies.

PMID- 20805199
TI  - To what extent have relaxed eligibility requirements and increased generosity of
      disability benefits acted as disincentives for employment? A systematic review of
      evidence from countries with well-developed welfare systems.
AB  - BACKGROUND: Reductions in the eligibility requirements and generosity of
      disability benefits have been introduced in several Organisation for Economic
      Cooperation and Development (OECD) countries in recent years, on the assumption
      that this will increase work incentives for people with chronic illness and
      disabilities. This paper systematically reviews the evidence for this assumption
      in the context of well-developed welfare systems. METHOD: Systematic review of
      all empirical studies from five OECD countries from 1970 to December 2009
      investigating the effect of changes in eligibility requirements or level of
      disability benefits on employment of disabled people. RESULTS: Sixteen studies
      were identified. Only one of five studies found that relaxed eligibility was
      significantly associated with a decline in employment. The most robust study
      found no significant effect. On generosity, eight out of 11 studies reported that
      benefit levels had a significant negative association with employment. The most
      robust study demonstrated a small but significant negative association.
      CONCLUSION: There was no firm evidence that changes in benefit eligibility
      requirements affected employment. While there was some evidence indicating that
      benefit level was negatively associated with employment, there was insufficient
      evidence of a high enough quality to determine the extent of that effect. Policy
      makers and researchers need to address the lack of a robust empirical basis for
      assessing the employment impact of these welfare reforms as well as potentially
      wider poverty impacts.

PMID- 20805200
TI  - Obstacles to health care transformation are numerous.

PMID- 20805198
TI  - Secular changes and predictors of adult height for 86 105 male and female members
      of the Thai Cohort Study born between 1940 and 1990.
AB  - BACKGROUND: Height trends can be useful indicators of population health but,
      despite Thailand's rapid socioeconomic development since the 1950s, few studies
      have examined accompanying secular changes in adult height or the effects of the
      transition on the heights of rural versus urban populations. This study therefore
      sought to document average heights in different age groups of rural and urban
      Thais and to investigate factors associated with attained height. METHODS: Data
      from 86,105 Thai Cohort Study participants was used to estimate mean heights for
      men and women in different birth year groups. Simple regression was used to
      calculate the change in height per decade of birth year among those based in
      rural or urban locations as children. Multiple linear regression was used to
      investigate effects of other childhood factors on height. RESULTS: Overall,
      average heights were found to have increased by approximately 1 cm per decade in
      those born between 1940 and 1990. However, the rate of increase was 0.4-0.5 cm
      per decade greater among urban-based Thais compared with those from the
      countryside. Parental education levels, household assets, birth size, sibling
      number, birth rank and region of residence were also significantly associated
      with adult height. CONCLUSIONS: These data suggest a marked secular increase in
      Thai heights in the second half of the 20th century probably reflecting improved
      childhood health and nutrition over this time. Rural-born Thais, who benefited to
      a lesser extent from the changes, may face future health challenges with greater
      risks of, among other things, obesity and its health consequences.

PMID- 20805202
TI  - Governments, pay for smoking cessation.

PMID- 20805204
TI  - [Ideology trumps evidence with new voluntary survey.].

PMID- 20805205
TI  - Prevention by the pound.

PMID- 20805206
TI  - Intestinal radiopacities in chronic renal failure.

PMID- 20805207
TI  - Intracerebral hemorrhage in a young man.

PMID- 20805208
TI  - Vancouver's supervised injection facility challenges Canada's drug laws.

PMID- 20805209
TI  - More evidence cannabis can help in neuropathic pain.

PMID- 20805211
TI  - The view from the Rock.

PMID- 20805212
TI  - Confidential reporting system for physicians' health proposed.

PMID- 20805213
TI  - Canada's doctors vote to discontinue financial support for CMAJ.

PMID- 20805210
TI  - Smoked cannabis for chronic neuropathic pain: a randomized controlled trial.
AB  - BACKGROUND: Chronic neuropathic pain affects 1%-2% of the adult population and is
      often refractory to standard pharmacologic treatment. Patients with chronic pain
      have reported using smoked cannabis to relieve pain, improve sleep and improve
      mood. METHODS: Adults with post-traumatic or postsurgical neuropathic pain were
      randomly assigned to receive cannabis at four potencies (0%, 2.5%, 6% and 9.4%
      tetrahydrocannabinol) over four 14-day periods in a crossover trial. Participants
      inhaled a single 25-mg dose through a pipe three times daily for the first five
      days in each cycle, followed by a nine-day washout period. Daily average pain
      intensity was measured using an 11-point numeric rating scale. We recorded
      effects on mood, sleep and quality of life, as well as adverse events. RESULTS:
      We recruited 23 participants (mean age 45.4 [standard deviation 12.3] years, 12
      women [52%]), of whom 21 completed the trial. The average daily pain intensity,
      measured on the 11-point numeric rating scale, was lower on the prespecified
      primary contrast of 9.4% v. 0% tetrahydrocannabinol (5.4 v. 6.1, respectively;
      difference = 0.7, 95% confidence interval [CI] 0.02-1.4). Preparations with
      intermediate potency yielded intermediate but nonsignificant degrees of relief.
      Participants receiving 9.4% tetrahydrocannabinol reported improved ability to
      fall asleep (easier, p = 0.001; faster, p < 0.001; more drowsy, p = 0.003) and
      improved quality of sleep (less wakefulness, p = 0.01) relative to 0%
      tetrahydrocannabinol. We found no differences in mood or quality of life. The
      most common drug-related adverse events during the period when participants
      received 9.4% tetrahydrocannabinol were headache, dry eyes, burning sensation in
      areas of neuropathic pain, dizziness, numbness and cough. CONCLUSION: A single
      inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis three times
      daily for five days reduced the intensity of pain, improved sleep and was well
      tolerated. Further long-term safety and efficacy studies are indicated.
      (International Standard Randomised Controlled Trial Register no. ISRCTN68314063).

PMID- 20805214
TI  - Systemic health reforms may be a prelude to privatization, new CMA president
      says.

PMID- 20805215
TI  - Doctors endorse development of patient charter.

PMID- 20805216
TI  - Flogging the transformation agenda.

PMID- 20805217
TI  - Nation's physicians urge re-opening of Canada Health Act.

PMID- 20805218
TI  - "Fuzzy" elements of CMA transformation blueprint may yet undermine medicare,
      critics say.

PMID- 20805219
TI  - The many faces of transformation.

PMID- 20805220
TI  - Prochloraz-induced oocyte maturation in rainbow trout (Oncorhynchus mykiss), a
      molecular and functional analysis.
AB  - In the present study, we aimed at characterizing the effect of prochloraz, an
      imidazole fungicide, on the oocyte meiotic maturation process in a freshwater
      teleost species, the rainbow trout (Oncorhynchus mykiss). Full-grown post
      vitellogenic ovarian follicles were incubated in vitro with prochloraz,
      Luteinizing Hormone (LH), or a combination of prochloraz and LH. The occurrence
      of oocyte maturation was assessed by monitoring germinal vesicle breakdown (GVBD)
      after 62-h in vitro incubation. Experiments were repeated in presence of
      actinomycin D, cycloheximide, or trilostane. The effect of prochloraz on the
      production of 17,20beta-dihydroxy-4-pregnen-3-one (17,20betaP), the natural
      maturation-inducing steroid, was quantified by radioimmunoassay. In addition, the
      effect of prochloraz on ovarian expression of 12 genes was monitored by real-time
      PCR. Prochloraz (10(-5)M) administered alone was able to induce 100% GVBD in the
      most responsive females. The occurrence of GVBD observed after prochloraz
      stimulation of follicles originating from various females was similar and highly
      correlated with the occurrence of GVBD observed after stimulation with low LH
      concentration. In addition, oocyte maturation induced by LH or prochloraz was
      totally inhibited by actinomycin D, cycloheximide, and trilostane. Similarly to
      LH, prochloraz was able to trigger 17,20betaP production by the ovarian follicle.
      Finally, prochloraz induced the overexpression of genes participating in
      17,20betaP production, intercellular communication, and paracrine control of
      preovulatory follicular differentiation such as igf, igf2, connexin 43, and
      20beta hydroxysteroid dehydrogenase (hsbd20). Together, our results demonstrate
      that prochloraz administered alone is able to trigger oocyte maturation through
      the induction of specific genes, some of them being also triggered by LH.
      Finally, our results clearly indicate that the effects of prochloraz and LH on
      oocyte maturation are synergistic.

PMID- 20805221
TI  - Structural and mechanistic classification of uronic acid-containing
      polysaccharide lyases.
AB  - Polysaccharide lyases (PLs) have been assigned to 21 families based on their
      sequences, with ~ 50 singletons awaiting further classification. For 19 of these
      families, the structure of at least one protein is known. In this review, we have
      analyzed the available structural information and show that presently known PL
      families belong to six general folds. Only two general catalytic mechanisms have
      been observed among these PLs: (1) metal-assisted neutralization of the acidic
      group of the sugar next to the cleaved bond, with, rather unusually, arginine or
      lysine playing the role of Bronsted base and (2) neutralization of the acidic
      group on the sugar by a close approach of an amino or acidic group forcing its
      protonation and Tyr or Tyr-His acting as the Bronsted base and acid.

PMID- 20805222
TI  - Sequences from the first fibronectin type III repeat of the neural cell adhesion
      molecule allow O-glycan polysialylation of an adhesion molecule chimera.
AB  - Polysialic acid is a developmentally regulated, anti-adhesive polymer that is
      added to N-glycans on the fifth immunoglobulin domain (Ig5) of the neural cell
      adhesion molecule (NCAM). We found that the first fibronectin type III repeat
      (FN1) of NCAM is required for the polysialylation of N-glycans on the adjacent
      Ig5 domain, and we proposed that the polysialyltransferases recognize specific
      sequences in FN1 to position themselves for Ig5 N-glycan polysialylation. Other
      studies identified a novel FN1 acidic surface patch and alpha-helix that play
      roles in NCAM polysialylation. Here, we characterize the contribution of two
      additional FN1 sequences, Pro(510)-Tyr(511)-Ser(512) (PYS) and Gln(516)-Val(517)
      Gln(518) (QVQ). Replacing PYS or the acidic patch dramatically decreases the O
      glycan polysialylation of a truncated NCAM protein, and replacing the alpha-helix
      or QVQ shifts polysialic acid to FN1 O-glycans in full-length NCAM. We also found
      that the FN1 domain of the olfactory cell adhesion molecule, a homologous but
      unpolysialylated protein, could partially replace NCAM FN1. Inserting Pro(510)
      Tyr(511) eliminated N-glycan polysialylation and enhanced O-glycosylation of an
      NCAM- olfactory cell adhesion molecule chimera, and inserting other FN1 sequences
      unique to NCAM, predominantly the acidic patch, created a new
      polysialyltransferase recognition site. Taken together, our results highlight the
      role of the FN1 alpha-helix and QVQ sequences in N-glycan polysialylation and
      demonstrate that the acidic patch primarily functions in O-glycan
      polysialylation.

PMID- 20805223
TI  - O-GlcNAc transferase regulates mitotic chromatin dynamics.
AB  - Mitosis must faithfully divide the genome such that each progeny inherits the
      same genetic material. DNA condensation is crucial in ensuring that chromosomes
      are correctly attached to the mitotic spindle for segregation, preventing DNA
      breaks or constrictions from the contractile ring. Histones form an octameric
      complex of basic proteins important in regulating DNA organization and
      accessibility. Histone post-translational modifications are altered during
      mitosis, although the roles of these post-translational modifications remain
      poorly characterized. Here, we report that N-acetylglucosamine (O-GlcNAc)
      transferase (OGT), the enzyme catalyzing the addition of O-GlcNAc moieties to
      nuclear and cytoplasmic proteins at serine and threonine residues, regulates some
      aspects of mitotic chromatin dynamics. OGT protein amounts decrease during M
      phase. Modest overexpression of OGT alters mitotic histone post-translational
      modifications at Lys-9, Ser-10, Arg-17, and Lys-27 of histone H3. Overexpression
      of OGT also prevents mitotic phosphorylation of coactivator-associated arginine
      methyltransferase 1 (CARM1) and prevents its correct cellular localization during
      mitosis. Moreover, OGT overexpression results in an increase in abnormal
      chromosomal bridge formation. Together, these results show that regulating the
      amount of OGT during mitosis is important in ensuring correct chromosomal
      segregation during mitosis.

PMID- 20805224
TI  - Seeded aggregation and toxicity of {alpha}-synuclein and tau: cellular models of
      neurodegenerative diseases.
AB  - The deposition of amyloid-like filaments in the brain is the central event in the
      pathogenesis of neurodegenerative diseases. Here we report cellular models of
      intracytoplasmic inclusions of alpha-synuclein, generated by introducing
      nucleation seeds into SH-SY5Y cells with a transfection reagent. Upon
      introduction of preformed seeds into cells overexpressing alpha-synuclein,
      abundant, highly filamentous alpha-synuclein-positive inclusions, which are
      extensively phosphorylated and ubiquitinated and partially thioflavin-positive,
      were formed within the cells. SH-SY5Y cells that formed such inclusions underwent
      cell death, which was blocked by small molecular compounds that inhibit beta
      sheet formation. Similar seed-dependent aggregation was observed in cells
      expressing four-repeat Tau by introducing four-repeat Tau fibrils but not three
      repeat Tau fibrils or alpha-synuclein fibrils. No aggregate formation was
      observed in cells overexpressing three-repeat Tau upon treatment with four-repeat
      Tau fibrils. Our cellular models thus provide evidence of nucleation-dependent
      and protein-specific polymerization of intracellular amyloid-like proteins in
      cultured cells.

PMID- 20805225
TI  - Activation of human VPS4A by ESCRT-III proteins reveals ability of substrates to
      relieve enzyme autoinhibition.
AB  - VPS4 proteins are AAA(+) ATPases required to form multivesicular bodies, release
      viral particles, and complete cytokinesis. They act by disassembling ESCRT-III
      heteropolymers during or after their proposed function in membrane scission. Here
      we show that purified human VPS4A is essentially inactive but can be stimulated
      to hydrolyze ATP by ESCRT-III proteins in a reaction that requires both their
      previously defined MIT interacting motifs and ~50 amino acids of the adjacent
      sequence. Importantly, C-terminal fragments of all ESCRT-III proteins tested,
      including CHMP2A, CHMP1B, CHMP3, CHMP4A, CHMP6, and CHMP5, activated VPS4A
      suggesting that it disassembles ESCRT-III heteropolymers by affecting each
      component protein. VPS4A is thought to act as a ring-shaped cylindrical oligomer
      like other AAA(+) ATPases, but this has been difficult to directly demonstrate.
      We found that concentrating His(6)-VPS4A on liposomes containing Ni(2+)
      nitrilotriacetic acid-tagged lipid increased ATP hydrolysis, confirming the
      importance of inter-subunit interactions for activity. We also found that
      mutating pore loops expected to line the center of a cylindrical oligomer changed
      the response of VPS4A to ESCRT-III proteins. Based on these data, we propose that
      ESCRT-III proteins facilitate assembly of functional but transient VPS4A
      oligomers and interact with sequences inside the pore of the assembled enzyme.
      Deleting the N-terminal MIT domain and adjacent linker from VPS4A increased both
      basal and liposome-enhanced ATPase activity, indicating that these elements play
      a role in autoinhibiting VPS4A until it encounters ESCRT-III proteins. These
      findings reveal new ways in which VPS4 activity is regulated and specifically
      directed to ESCRT-III polymers.

PMID- 20805227
TI  - Conformational dynamics of the bovine mitochondrial ADP/ATP carrier isoform 1
      revealed by hydrogen/deuterium exchange coupled to mass spectrometry.
AB  - The mitochondrial adenine nucleotide carrier (Ancp) catalyzes the transport of
      ADP and ATP across the mitochondrial inner membrane, thus playing an essential
      role in cellular energy metabolism. During the transport mechanism the carrier
      switches between two different conformations that can be blocked by two toxins:
      carboxyatractyloside (CATR) and bongkrekic acid. Therefore, our understanding of
      the nucleotide transport mechanism can be improved by analyzing structural
      differences of the individual inhibited states. We have solved the three
      dimensional structure of bovine carrier isoform 1 (bAnc1p) in a complex with
      CATR, but the structure of the carrier-bongkrekic acid complex, and thus, the
      detailed mechanism of transport remains unknown. Improvements in sample
      processing in the hydrogen/deuterium exchange technique coupled to mass
      spectrometry (HDX-MS) have allowed us to gain novel insights into the
      conformational changes undergone by bAnc1p. This paper describes the first study
      of bAnc1p using HDX-MS. Results obtained with the CATR-bAnc1p complex were fully
      in agreement with published results, thus, validating our approach. On the other
      hand, the HDX kinetics of the two complexes displays marked differences. The
      bongkrekic acid-bAnc1p complex exhibits greater accessibility to the solvent on
      the matrix side, whereas the CATR-bAnc1p complex is more accessible on the
      intermembrane side. These results are discussed with respect to the structural
      and biochemical data available on Ancp.

PMID- 20805226
TI  - Palmitate-induced down-regulation of sortilin and impaired GLUT4 trafficking in
      C2C12 myotubes.
AB  - Elevated saturated FFAs including palmitate (C16:0) are a primary trigger for
      peripheral insulin resistance characterized by impaired glucose uptake/disposal
      in skeletal muscle, resulting from impaired GLUT4 translocation in response to
      insulin. We herein demonstrate that palmitate induces down-regulation of
      sortilin, a sorting receptor implicated in the formation of insulin-responsive
      GLUT4 vesicles, via mechanisms involving PKC and TNF-alpha-converting enzyme, but
      not p38, JNK, or mitochondrial reactive oxygen species generation, leading to
      impaired GLUT4 trafficking in C2C12 myotubes. Intriguingly, unsaturated FFAs such
      as palmitoleate (C16:1) and oleate (C18:1) had no such detrimental effects,
      appearing instead to effectively reverse palmitate-induced impairment of insulin
      responsive GLUT4 recycling along with restoration of sortilin abundance by
      preventing aberrant PKC activation. On the other hand, shRNA-mediated reduction
      of sortilin in intact C2C12 myotubes inhibited insulin-induced GLUT4 recycling
      without dampening Akt phosphorylation. We found that the peroxisome proliferator
      activated receptor gamma agonist troglitazone prevented the palmitate-induced
      sortilin reduction and also ameliorated insulin-responsive GLUT4 recycling
      without altering the palmitate-evoked insults on signaling cascades; neither
      highly phosphorylated PKC states nor impaired insulin-responsive Akt
      phosphorylation was affected. Taken together, our data provide novel insights
      into the pathogenesis of PKC-dependent insulin resistance with respect to insulin
      responsive GLUT4 translocation, which could occur not only through defects of
      insulin signaling but also via a reduction of sortilin, which directly controls
      trafficking/sorting of GLUT4 in skeletal muscle cells. In addition, our data
      suggest the insulin-sensitizing action of peroxisome proliferator-activated
      receptor gamma agonists to be at least partially mediated through the restoration
      of proper GLUT4 trafficking/sorting events governed by sortilin.

PMID- 20805230
TI  - Peer relationships of deaf children with cochlear implants: predictors of peer
      entry and peer interaction success.
AB  - This study investigated factors that affect the development of positive peer
      relationships among deaf children with cochlear implants. Ten 5- to 6-year-old
      deaf children with implants were observed under conditions varying peer context
      difficulty in a Peer Entry task. Results revealed better outcomes for deaf
      children interacting in one-on-one situations compared to interactions including
      two other hearing children and better performance among girls than boys. In
      addition, longer duration of implant use and higher self-esteem were associated
      with better performance on the Peer Task, which was in turn related to parental
      reports of children's social functioning outside the experimental situation.
      These findings contribute to the growing literature describing the benefits of
      cochlear implantation in the areas of communication and socialization, while
      pointing to interventions that may enhance deaf children's social competence.

PMID- 20805229
TI  - Laminin-3B11, a novel vascular-type laminin capable of inducing prominent
      lamellipodial protrusions in microvascular endothelial cells.
AB  - The basement membrane (BM) proteins laminins, which consist of alpha, beta, and
      gamma chains, support tissue structures and cellular functions. To date only
      alpha4 and alpha5 types of laminins have been identified in the BMs of blood
      vessels. Our recent study suggested the presence of novel alpha3B-containing
      laminins in vascular BMs. Here we identified and characterized the third member
      of vascular laminins, laminin-3B11 (Lm3B11). RT-PCR analysis showed that
      microvascular endothelial (MVE) cells and umbilical vein endothelial cells
      expressed the messages for the alpha3B, beta1, beta2, and gamma1 chains. In the
      culture of MVE cells, alpha3B was associated with beta1 and gamma1, producing
      Lm3B11. Recombinant Lm3B11 was overexpressed by introducing the cDNAs of the
      three chains into HEK-293 cells and purified to homogeneity. Purified Lm3B11
      exhibited relatively weak cell adhesion activity through both alpha3beta1 and
      alpha6beta1 integrins. Most characteristically, Lm3B11 strongly stimulated MVE
      cells to extend many lamellipodial protrusions. This pseudopodial branching was
      blocked by an inhibitor for Src or phosphatidylinositol 3-kinase. Consistently,
      Lm3B11 stimulated the phosphorylation of Src and Akt more strongly than other
      laminins, suggesting that the integrin-derived signaling is mediated by these
      factors. The unique activity of Lm3B11 appears to be favorable to the branching
      of capillaries and venules.

PMID- 20805228
TI  - The antioxidant transcription factor Nrf2 negatively regulates autophagy and
      growth arrest induced by the anticancer redox agent mitoquinone.
AB  - Mitoquinone (MitoQ) is a synthetically modified, redox-active ubiquinone compound
      that accumulates predominantly in mitochondria. We found that MitoQ is 30-fold
      more cytotoxic to breast cancer cells than to healthy mammary cells. MitoQ
      treatment led to irreversible inhibition of clonogenic growth of breast cancer
      cells through a combination of autophagy and apoptotic cell death mechanisms.
      Relatively limited cytotoxicity was seen with the parent ubiquinone coenzyme
      Q(10.) Inhibition of cancer cell growth by MitoQ was associated with G(1)/S cell
      cycle arrest and phosphorylation of the checkpoint kinases Chk1 and Chk2. The
      possible role of oxidative stress in MitoQ activity was investigated by measuring
      the products of hydroethidine oxidation. Increases in ethidium and
      dihydroethidium levels, markers of one-electron oxidation of hydroethidine, were
      observed at cytotoxic concentrations of MitoQ. Keap1, an oxidative stress sensor
      protein that regulates the antioxidant transcription factor Nrf2, underwent
      oxidation, degradation, and dissociation from Nrf2 in MitoQ-treated cells. Nrf2
      protein levels, nuclear localization, and transcriptional activity also increased
      following MitoQ treatment. Knockdown of Nrf2 caused a 2-fold increase in
      autophagy and an increase in G(1) cell cycle arrest in response to MitoQ but had
      no apparent effect on apoptosis. The Nrf2-regulated enzyme NQO1 is partly
      responsible for controlling the level of autophagy. Keap1 and Nrf2 act as redox
      sensors for oxidative perturbations that lead to autophagy. MitoQ and similar
      compounds should be further evaluated for novel anticancer activity.

PMID- 20805235
TI  - Building orphan competent communities: experiences from a community-based capital
      cash transfer initiative in Kenya.
AB  - As a result of the increasing number of orphans in sub-Saharan Africa, numerous
      programmes have been initiated to facilitate the care and support of orphaned and
      vulnerable children. This paper reports on a community-based capital cash
      transfer initiative in Kenya and explores its role in building orphan competent
      and supportive communities through its participatory project cycle. Using a
      mixture of individual and group interviews, 300 orphaned children and 110 adults
      involved in this initiative were interviewed using open-ended questions. A
      thematic analysis of the data revealed that many of the communities participating
      in this programme had become more united and active in the support of orphaned
      children following the mobilization of much needed economic, political and social
      support resources. Despite many difficulties, largely due to the complexity of
      communities, we conclude that community-based capital cash transfer initiatives
      can facilitate the building of orphan competent communities.

PMID- 20805236
TI  - A neuronal basis for task-negative responses in the human brain.
AB  - Neuroimaging studies have revealed a number of brain regions that show a reduced
      blood oxygenation level-dependent (BOLD) signal during externally directed tasks
      compared with a resting baseline. These regions constitute a network whose
      operation has become known as the default mode. The source of functional magnetic
      resonance imaging (fMRI) signal reductions in the default mode during task
      performance has not been resolved, however. It may be attributable to neuronal
      effects (neuronal firing), physiological effects (e.g., task vs. rest differences
      in respiration rate), or even increases in neuronal activity with an atypical
      blood response. To establish the source of signal decreases in the default mode,
      we used the calibrated fMRI method to quantify changes in the cerebral metabolic
      rate of oxygen (CMRO2) and cerebral blood flow (CBF) in those regions that
      typically show reductions in BOLD signal during a demanding cognitive task.
      CBF:CMRO2 coupling during task-negative responses were linear, with a coupling
      constant similar to that in task-positive regions, indicating a neuronal source
      for signal reductions in multiple brain areas. We also identify, for the first
      time, two modes of neuronal activity in this network; one in which greater
      deactivation (characterized by metabolic rate reductions) is associated with more
      effort and one where it is associated with less effort.

PMID- 20805237
TI  - Electrocortical dynamics reflect age-related differences in movement kinematics
      among children and adults.
AB  - Previous neuroimaging and behavioral studies demonstrated structural and
      functional changes in the motor system across childhood. However, it is unclear
      what functionally relevant electrocortical processes underlie developmental
      differences in motor planning and control during multijoint, goal-directed
      movements. The current study characterized age-related differences in
      electrocortical processes during the performance of discrete aiming movements in
      children and adults. Electroencephalography and movement kinematics were recorded
      from 3 groups of participants (n = 15 each): young children (mean 6.7 years),
      older children (mean 10.2 years), and adults (mean 22.1 years). Age-related
      differences were evident in the electroencephalographic (EEG) signals. First,
      young children exhibited less movement-related activity in task-relevant motor
      areas compared with adults (movement-related cortical potentials). Second, young
      children exhibited greater activation (less alpha power) of the frontal areas and
      less activation of the parietal areas as compared with the other groups. At the
      behavioral level, young children made slower and jerkier movements, with less
      consistent directional planning compared with older children and adults.
      Significant correlations were also found between EEG and movement kinematic
      measures. Taken together, the results of this study provide evidence that age
      related differences in the quality of motor planning and performance are
      reflected in the differences in electrocortical dynamics among children and
      adults.

PMID- 20805238
TI  - The effect of midlife physical activity on cognitive function among older adults:
      AGES--Reykjavik Study.
AB  - BACKGROUND: There are few studies on the long-term associations of physical
      activity (PA) to cognition. Here, we examine the association of midlife PA to
      late-life cognitive function and dementia. METHODS: The sample consisted of a
      population-based cohort of men and women (born in 1907-1935) participating in the
      Age Gene/Environment Susceptibility-Reykjavik Study. The interval between the
      midlife ascertainment of PA and late-life cognitive function was 26 years.
      Composite scores of speed of processing, memory, and executive function were
      assessed with a battery of neuropsychological tests, and dementia was diagnosed
      according to international guidelines. There were 4,761 nondemented participants
      and 184 (3.7%) with a diagnosis of dementia, with complete data for the analysis.
      RESULTS: Among the participants, no midlife PA was reported by 68.8%, <= 5 hours
      PA by 26.5%, and >5 hours PA by 4.5%. Excluding participants with dementia
      compared with the no PA group, both PA groups had significantly faster speed of
      processing (<= 5 hours, beta = .22; >5 hours, beta = .32, p trend < .0001),
      better memory (<= 5 hours, beta = .15; >5 hours, beta = .18, p trend < .0001),
      and executive function (<= 5 hours, beta = .09; >5 hours, beta = .18, p trend<
      .0001), after controlling for demographic and cardiovascular factors. The <= 5
      hours PA group was significantly less likely to have dementia in late life (odds
      ratio: 0.6, 95% confidence interval: 0.40-0.88) after adjusting for confounders.
      CONCLUSION: Midlife PA may contribute to maintenance of cognitive function and
      may reduce or delay the risk of late-life dementia.

PMID- 20805239
TI  - Premature centromere division of metaphase chromosomes in peripheral blood
      lymphocytes of Alzheimer's disease patients: relation to gender and age.
AB  - Chromosomal alterations are a feature of both aging and Alzheimer's disease (AD).
      This study examined if premature centromere division (PCD), a chromosomal
      instability indicator increased in AD, is correlated with aging or, instead,
      represents a de novo chromosomal alteration due to accelerating aging in AD. PCD
      in peripheral blood lymphocytes was determined in sporadic AD patients and gender
      and age-matched unaffected controls. Metaphase nuclei were analyzed for
      chromosomes showing PCD, X chromosomes with PCD (PCD,X), and acrocentric
      chromosomes showing PCD. AD patients, regardless of age, demonstrated increased
      PCD on any chromosome and PCD on acrocentric chromosomes in both genders, whereas
      an increase in frequency of PCD,X was expressed only in women. This cytogenetic
      analysis suggests that PCD is a feature of AD, rather than an epiphenomenon of
      chronological aging, and may be useful as a physiological biomarker that can be
      used for disease diagnosis.

PMID- 20805240
TI  - FragGeneScan: predicting genes in short and error-prone reads.
AB  - The advances of next-generation sequencing technology have facilitated
      metagenomics research that attempts to determine directly the whole collection of
      genetic material within an environmental sample (i.e. the metagenome).
      Identification of genes directly from short reads has become an important yet
      challenging problem in annotating metagenomes, since the assembly of metagenomes
      is often not available. Gene predictors developed for whole genomes (e.g.
      Glimmer) and recently developed for metagenomic sequences (e.g. MetaGene) show a
      significant decrease in performance as the sequencing error rates increase, or as
      reads get shorter. We have developed a novel gene prediction method FragGeneScan,
      which combines sequencing error models and codon usages in a hidden Markov model
      to improve the prediction of protein-coding region in short reads. The
      performance of FragGeneScan was comparable to Glimmer and MetaGene for complete
      genomes. But for short reads, FragGeneScan consistently outperformed MetaGene
      (accuracy improved ~62% for reads of 400 bases with 1% sequencing errors, and
      ~18% for short reads of 100 bases that are error free). When applied to
      metagenomes, FragGeneScan recovered substantially more genes than MetaGene
      predicted (>90% of the genes identified by homology search), and many novel genes
      with no homologs in current protein sequence database.

PMID- 20805241
TI  - Modular pathways for editing non-cognate amino acids by human cytoplasmic leucyl
      tRNA synthetase.
AB  - To prevent potential errors in protein synthesis, some aminoacyl-transfer RNA
      (tRNA) synthetases have evolved editing mechanisms to hydrolyze misactivated
      amino acids (pre-transfer editing) or misacylated tRNAs (post-transfer editing).
      Class Ia leucyl-tRNA synthetase (LeuRS) may misactivate various natural and non
      protein amino acids and then mischarge tRNA(Leu). It is known that the fidelity
      of prokaryotic LeuRS depends on multiple editing pathways to clear the incorrect
      intermediates and products in the every step of aminoacylation reaction. Here, we
      obtained human cytoplasmic LeuRS (hcLeuRS) and tRNA(Leu) (hctRNA(Leu)) with high
      activity from Escherichia coli overproducing strains to study the synthetic and
      editing properties of the enzyme. We revealed that hcLeuRS could adjust its
      editing strategy against different non-cognate amino acids. HcLeuRS edits
      norvaline predominantly by post-transfer editing; however, it uses mainly pre
      transfer editing to edit alpha-amino butyrate, although both amino acids can be
      charged to tRNA(Leu). Post-transfer editing as a final checkpoint of the reaction
      was very important to prevent mis-incorporation in vitro. These results provide
      insight into the modular editing pathways created to prevent genetic code
      ambiguity by evolution.

PMID- 20805242
TI  - Efficient use of accessibility in microRNA target prediction.
AB  - Considering accessibility of the 3'UTR is believed to increase the precision of
      microRNA target predictions. We show that, contrary to common belief, ranking by
      the hybridization energy or by the sum of the opening and hybridization energies,
      used in currently available algorithms, is not an efficient way to rank
      predictions. Instead, we describe an algorithm which also considers only the
      accessible binding sites but which ranks predictions according to over
      representation. When compared with experimentally validated and refuted targets
      in the fruit fly and human, our algorithm shows a remarkable improvement in
      precision while significantly reducing the computational cost in comparison with
      other free energy based methods. In the human genome, our algorithm has at least
      twice higher precision than other methods with their default parameters. In the
      fruit fly, we find five times more validated targets among the top 500
      predictions than other methods with their default parameters. Furthermore, using
      a common statistical framework we demonstrate explicitly the advantages of using
      the canonical ensemble instead of using the minimum free energy structure alone.
      We also find that 'naive' global folding sometimes outperforms the local folding
      approach.

PMID- 20805243
TI  - Structural insights into cis element recognition of non-polyadenylated RNAs by
      the Nab3-RRM.
AB  - Transcription termination of non-polyadenylated RNAs in Saccharomyces cerevisiae
      occurs through the action of the Nrd1-Nab3-Sen1 complex. Part of the decision to
      terminate via this pathway occurs via direct recognition of sequences within the
      nascent transcript by RNA recognition motifs (RRMs) within Nrd1 and Nab3. Here we
      present the 1.6 A structure of Nab3-RRM bound to its UCUU recognition sequence.
      The crystal structure reveals clear density for a UCU trinucleotide and a fourth
      putative U binding site. Nab3-RRM establishes a clear preference for the central
      cytidine of the UCUU motif, which forms pseudo-base pairing interactions
      primarily through hydrogen bonds to main chain atoms and one serine hydroxyl
      group. Specificity for the flanking uridines is less defined; however, binding
      experiments confirm that these residues are also important for high affinity
      binding. Comparison of the Nab3-RRM to other structures of RRMs bound to
      polypyrimidine RNAs showed that this mode of recognition is similar to what is
      observed for the polypyrimidine-tract binding RRMs, and that the serine residue
      involved in pseudo-base pairing is only found in RRMs that bind to polypyrimidine
      RNAs that contain a cytosine base, suggesting a possible mechanism for
      discriminating between cytosine and uracil bases in RRMs that bind to
      polypyrimidine-containing RNA.

PMID- 20805244
TI  - Analysis of two human pre-ribosomal factors, bystin and hTsr1, highlights
      differences in evolution of ribosome biogenesis between yeast and mammals.
AB  - Recent studies reveal that maturation of the 40S ribosomal subunit precursors in
      mammals includes an additional step during processing of the internal transcribed
      spacer 1 (ITS1), when compared with yeast Saccharomyces cerevisiae, even though
      the protein content of the pre-40S particle appears to be the same. Here, we
      examine by depletion with siRNA treatment the function of human orthologs of two
      essential yeast pre-ribosomal factors, hEnp1/bystin and hTsr1. Like their yeast
      orthologs, bystin is required for efficient cleavage of the ITS1 and further
      processing of this domain within the pre-40S particles, whereas hTsr1 is
      necessary for the final maturation steps. However, bystin depletion leads to
      accumulation of an unusual 18S rRNA precursor, revealing a new step in ITS1
      processing that potentially involves an exonuclease. In addition, pre-40S
      particles lacking hTsr1 are partially retained in the nucleus, whereas depletion
      of Tsr1p in yeast results in strong cytoplasmic accumulation of pre-40S
      particles. These data indicate that ITS1 processing in human cells may be more
      complex than currently envisioned and that coordination between maturation and
      nuclear export of pre-40S particles has evolved differently in yeast and
      mammalian cells.

PMID- 20805245
TI  - Highly redundant function of multiple AT-rich sequences as core promoter elements
      in the TATA-less RPS5 promoter of Saccharomyces cerevisiae.
AB  - In eukaryotes, protein-coding genes are transcribed by RNA polymerase II (pol II)
      together with general transcription factors (GTFs). TFIID, the largest GTF
      composed of TATA element-binding protein (TBP) and 14 TBP-associated factors
      (TAFs), plays a critical role in transcription from TATA-less promoters. In
      metazoans, several core promoter elements other than the TATA element are thought
      to be recognition sites for TFIID. However, it is unclear whether functionally
      homologous elements also exist in TATA-less promoters in Saccharomyces
      cerevisiae. Here, we identify the cis-elements required to support normal levels
      of transcription and accurate initiation from sites within the TATA-less and
      TFIID-dependent RPS5 core promoter. Systematic mutational analyses show that
      multiple AT-rich sequences are required for these activities and appear to
      function as recognition sites for TFIID. A single copy of these sequences can
      support accurate initiation from the endogenous promoter, indicating that they
      carry highly redundant functions. These results show a novel architecture of
      yeast TATA-less promoters and support a model in which pol II scans DNA
      downstream from a recruited site, while searching for appropriate initiation
      site(s).

PMID- 20805247
TI  - MEF/ELF4 transactivation by E2F1 is inhibited by p53.
AB  - Myeloid elf-1-like factor (MEF) or Elf4 is an E-twenty-six (ETS)-related
      transcription factor with strong transcriptional activity that influences
      cellular senescence by affecting tumor suppressor p53. MEF downregulates p53
      expression and inhibits p53-mediated cellular senescence by transcriptionally
      activating MDM2. However, whether p53 reciprocally opposes MEF remains
      unexplored. Here, we show that MEF is modulated by p53 in human cells and mice
      tissues. MEF expression and promoter activity were suppressed by p53. While we
      found that MEF promoter does not contain p53 response elements, intriguingly, it
      contains E2F consensus sites. Subsequently, we determined that E2F1 specifically
      binds to MEF promoter and transactivates MEF. Nevertheless, E2F1 DNA binding and
      transactivation of MEF promoter was inhibited by p53 through the association
      between p53 and E2F1. Furthermore, we showed that activation of p53 in
      doxorubicin-induced senescent cells increased E2F1 and p53 interaction,
      diminished E2F1 recruitment to MEF promoter and reduced MEF expression. These
      observations suggest that p53 downregulates MEF by associating with and
      inhibiting the binding activity of E2F1, a novel transcriptional activator of
      MEF. Together with previous findings, our present results indicate that a
      negative regulatory mechanism exists between p53 and MEF.

PMID- 20805248
TI  - Co-regulation of alternative splicing by diverse splicing factors in
      Caenorhabditis elegans.
AB  - Regulation of alternative splicing is controlled by pre-mRNA sequences (cis
      elements) and trans-acting protein factors that bind them. The combinatorial
      interactions of multiple protein factors with the cis-elements surrounding a
      given alternative splicing event lead to an integrated splicing decision. The
      mechanism of multifactorial splicing regulation is poorly understood. Using a
      splicing-sensitive DNA microarray, we assayed 352 Caenorhabditis elegans
      alternative cassette exons for changes in embryonic splicing patterns between
      wild-type and 12 different strains carrying mutations in a splicing factor. We
      identified many alternative splicing events that are regulated by multiple
      splicing factors. Many splicing factors have the ability to behave as splicing
      repressors for some alternative cassette exons and as splicing activators for
      others. Unexpectedly, we found that the ability of a given alternative splicing
      factor to behave as an enhancer or repressor of a specific splicing event can
      change during development. Our observations that splicing factors can change
      their effects on a substrate during development support a model in which
      combinatorial effects of multiple factors, both constitutive and developmentally
      regulated ones, contribute to the overall splicing decision.

PMID- 20805249
TI  - Psychosocial factors and major adverse cardiac and cerebrovascular events after
      cardiac surgery.
AB  - Our aim was to prospectively examine the association of psychosocial factors with
      adverse outcome after cardiac surgery. One hundred and eighty cardiac surgery
      patients were enrolled and contacted annually by mail. Depression [Beck
      depression inventory (BDI)], anxiety [state anxiety subscale in Spielberger State
      Trait Anxiety Inventory (STAI-S) and trait anxiety subscale in Spielberger State
      Trait Anxiety Inventory (STAI-T)] were investigated annually, social support,
      negative affectivity, social inhibition (SI), illness intrusiveness, self-rated
      health and sleeping disorders were investigated by standardized tests at the
      second and fifth year. The end-point was the major adverse cardiac and
      cerebrovascular event (MACCE) including death. Twenty-eight (15.5%) patients died
      by the end of the fifth year. At the end of the second and fifth years, 146
      (81.1%) and 118 (65.5%) patients fulfilled the tests, respectively. At the end of
      the second year after adjustment for medical and perioperative factors worse self
      rated health [adjusted hazard ratio (AHR): 0.67, P=0.006], sleeping disorders
      (AHR: 1.14, P=0.001), higher illness intrusiveness (AHR: 1.03, P=0.018), higher
      BDI (AHR: 1.12, P=0.001), STAI-S (AHR: 1.09, P=0.001) and higher STAI-T scores
      (AHR: 1.08, P=0.002) showed higher risk for MACCE. Significant individual
      elevation in scores of sleeping disorders, illness intrusiveness and SI were
      observed over the three-year period in the MACCE group. Assessment of
      psychosocial factors could help in identifying patients at high-risk for MACCE
      after cardiac surgery.

PMID- 20805246
TI  - Natural and engineered nicking endonucleases--from cleavage mechanism to
      engineering of strand-specificity.
AB  - Restriction endonucleases (REases) are highly specific DNA scissors that have
      facilitated the development of modern molecular biology. Intensive studies of
      double strand (ds) cleavage activity of Type IIP REases, which recognize 4-8 bp
      palindromic sequences, have revealed a variety of mechanisms of molecular
      recognition and catalysis. Less well-studied are REases which cleave only one of
      the strands of dsDNA, creating a nick instead of a ds break. Naturally occurring
      nicking endonucleases (NEases) range from frequent cutters such as Nt.CviPII
      (^CCD; ^ denotes the cleavage site) to rare-cutting homing endonucleases (HEases)
      such as I-HmuI. In addition to these bona fida NEases, individual subunits of
      some heterodimeric Type IIS REases have recently been shown to be natural NEases.
      The discovery and characterization of more REases that recognize asymmetric
      sequences, particularly Types IIS and IIA REases, has revealed recognition and
      cleavage mechanisms drastically different from the canonical Type IIP mechanisms,
      and has allowed researchers to engineer highly strand-specific NEases. Monomeric
      LAGLIDADG HEases use two separate catalytic sites for cleavage. Exploitation of
      this characteristic has also resulted in useful nicking HEases. This review aims
      at providing an overview of the cleavage mechanisms of Types IIS and IIA REases
      and LAGLIDADG HEases, the engineering of their nicking variants, and the
      applications of NEases and nicking HEases.

PMID- 20805250
TI  - Modifications to Ivor Lewis esophagectomy.
AB  - The surgical approach to esophagectomy is variable. A number of factors are
      considered when determining the optimal approach to esophagectomy: location and
      extent of disease, fibrosis, additional patient factors and surgeon preference.
      One of the disadvantages to some approaches is the need for a change in position,
      which increases operative time. Also, because typically the abdomen is initially
      explored, patients may later be deemed unresectable at thoracotomy. We describe
      time saving modifications to the standard Ivor Lewis esophagectomy that eliminate
      the need for repositioning and facilitate a stapled end-to-end anastomosis.

PMID- 20805251
TI  - Surgical management of unusual gastrointestinal bleeding and a left ventricular
      assist device.
AB  - There is growing evidence that patients treated with continuous flow ventricular
      assist devices are at increased risk for bleeding complications beyond what would
      be expected for those requiring anti-coagulation therapy. However, the management
      of these patients is typically medical. We present a case of unusual
      gastrointestinal bleeding successfully managed with surgical intervention in a
      patient with a Heartmate II ventricular assist device.

PMID- 20805252
TI  - An unusual manifestation of left partial anomalous pulmonary venous connection.
AB  - A 68-year-old male patient had aortic valve replacement for aortic valve
      endocarditis. The central line (left) position looked abnormal on chest X-ray.
      Contrast studies confirmed left sided partial anomalous pulmonary venous
      connection.

PMID- 20805253
TI  - Incidence and risk factors for pacemaker implantation following aortic valve
      replacement.
AB  - Our aim was to identify the predictive factors for permanent pacemaker (PM)
      implantation in patients undergoing isolated aortic valve replacement (AVR). A
      total of 3534 patients received an AVR between January 1990 and December 2003 in
      our institution. Permanent PM implantation was performed in 234 (6.6%) patients,
      over median time of three days (range one to 24 days). This patient population
      was compared to a random sample of 191 patients undergoing AVR without permanent
      PM implantation. The overall mean age was 63.5 years (+/-14.2) and 261 patients
      (62%) were male. Univariate and multivariate logistic regression analysis of pre-
      and perioperative data were performed. Overall the 30 days mortality was 4.2%
      (10/234) in patients with PM and 1% (2/191) in the control group (P=0.046).
      Patients with PMs were older (P<0.001), had more additional coronary artery
      bypass grafting (CABG) surgery or mitral valve replacement (MVR) (P<0.001),
      complete right bundle branch block (RBBB) prior to surgery, and more frequently
      underwent re-operations compared to patients without PMs (P<0.001). The
      multivariate logistic regression model with PM implantation as the dependent
      variable demonstrated that older age was not independently associated with PM
      implantation. As independent predictors concomitant severe mitral valve
      insufficiency, CABG, subaortic stenosis (SAS) or re-do operations were
      identified.

PMID- 20805254
TI  - Acute graft pyelonephritis in renal transplant recipients: incidence, risk
      factors and long-term outcome.
AB  - BACKGROUND: The influence of acute graft pyelonephritis (AGPN) on graft outcome
      in renal transplant recipients still remains controversial. METHODS: We
      retrospectively analysed 189 patients (113 males; mean age: 49.7 +/- 13.1 years)
      undergoing renal transplantation at the University Hospital 12 de Octubre
      (Madrid, Spain) from January 2002 to December 2004, with a minimum follow-up of
      36 months. Factors associated with AGPN were assessed by logistic regression
      analysis. Long-term graft function was compared according to the occurrence of
      this complication during follow-up. 'Decline in renal graft function' was defined
      as the increase in serum creatinine (SC) levels > 0.33 mg/dL between Month 3 and
      Year 1 after transplantation. RESULTS: Nineteen patients (10.0%) were diagnosed
      with 25 episodes of AGPN (incidence rate: 4.4 episodes per 100 patient-years).
      The presence of glomerulonephritis as the underlying disease [odds ratio (OR)
      4.2; 95% confidence interval (95%CI): 1.3-14.1] and the previous occurrence of
      two to five (OR 9.4; 95%CI: 1.5-56.8) or more than five episodes of asymptomatic
      bacteriuria after transplantation (OR 19.8; 95%CI: 2.4-160.2) emerged as
      independent predictors for AGPN. A near-significant association was found for
      cytomegalovirus infection (OR 4.2; 95%CI: 0.9-18.4), whereas receiving a single
      kidney transplant (vs. double-kidney) showed a protective effect (OR 0.2; 95%CI:
      0.0-0.8). During the 36-month follow-up, levels of SC, creatinine clearance and
      24-h proteinuria did not differ significantly between patients with or without
      AGPN, and this complication did not exert any effect on the risk for decline in
      renal graft function. CONCLUSIONS: AGPN does not impair long-term graft function
      in renal transplant recipients.

PMID- 20805255
TI  - Racial/ethnic differences in association of fasting glucose-associated genomic
      loci with fasting glucose, HOMA-B, and impaired fasting glucose in the U.S. adult
      population.
AB  - OBJECTIVE: To estimate allele frequencies and the marginal and combined effects
      of novel fasting glucose (FG)-associated single nucleotide polymorphisms (SNPs)
      on FG levels and on risk of impaired FG (IFG) among non-Hispanic white, non
      Hispanic black, and Mexican Americans. RESEARCH DESIGN AND METHODS: DNA samples
      from 3,024 adult fasting participants in the National Health and Nutrition
      Examination Survey (NHANES) III (1991-1994) were genotyped for 16 novel FG
      associated SNPs in multiple genes. We determined the allele frequencies and
      influence of these SNPs alone and in a weighted genetic risk score on FG,
      homeostasis model assessment of beta-cell function (HOMA-B), and IFG by
      race/ethnicity, while adjusting for age and sex. RESULTS: All allele frequencies
      varied significantly by race/ethnicity. A weighted genetic risk score, based on
      16 SNPs, was associated with a 0.022 mmol/l (95% CI 0.009-0.035), 0.036 mmol/l
      (0.019-0.052), and 0.033 mmol/l (0.020-0.046) increase in FG levels per risk
      allele among non-Hispanic whites, non-Hispanic blacks, and Mexican Americans,
      respectively. Adjusted odds ratios for IFG were 1.78 for non-Hispanic whites (95%
      CI 1.00-3.17), 2.40 for non-Hispanic blacks (1.07-5.37), and 2.39 for Mexican
      Americans (1.37-4.14) when we compared the highest with the lowest quintiles of
      genetic risk score (P=0.365 for testing heterogeneity of effect across
      race/ethnicity). CONCLUSIONS: We conclude that allele frequencies of 16 novel FG
      associated SNPs vary significantly by race/ethnicity, but the influence of these
      SNPs on FG levels, HOMA-B, and IFG were generally consistent across all
      racial/ethnic groups.

PMID- 20805257
TI  - Health-related quality of life and mortality in a general and elderly population
      of patients with type 2 diabetes (ZODIAC-18).
AB  - OBJECTIVE: Diabetes negatively impacts the health-related quality of life (HRQOL)
      of patients with type 2 diabetes. An earlier analysis showed HRQOL to be
      associated with mortality, which suggests that measuring HRQOL could have
      clinical implications. We studied the association between HRQOL and total and
      cardiovascular mortality in patients with type 2 diabetes during long-term follow
      up and specifically focused on old age and sex differences. RESEARCH DESIGN AND
      METHODS: HRQOL was measured in a prospectively followed cohort of 1,353 patients
      with type 2 diabetes using the RAND-36. Cox proportional hazard models were used
      to measure the independent effect of baseline HRQOL on mortality. RESULTS: During
      a mean follow-up of 9.6 years, 570 (42%) patients died, 280 of whom died of
      cardiovascular disease (49%). The Physical Component Score (PCS) and the Mental
      Component Score (MCS) were inversely associated with total mortality, with hazard
      ratios of 0.988 (95% CI 0.983-0.993) and 0.990 (95% CI 0.985-0.995),
      respectively. A 10-point-higher score on the PCS and MCS decreased the risk for
      total mortality by 11 and 10%, respectively. An inverse relationship with
      mortality was also seen for men, women, and for patients aged>75 years. Mental
      health was significantly related to mortality in men but not in women.
      CONCLUSIONS: Lower physical and mental HRQOL was associated with a higher total
      mortality and cardiovascular mortality in patients with type 2 diabetes; this is
      also the case when studying men and women and the elderly separately. The
      dimension mental health, related to depression and anxiety, was only associated
      with mortality in men, not in women.

PMID- 20805258
TI  - Glulisine versus human regular insulin in combination with glargine in
      noncritically ill hospitalized patients with type 2 diabetes: a randomized double
      blind study.
AB  - OBJECTIVE: To compare the efficacy and safety of the rapid-acting insulin analog
      glulisine and regular insulin in hyperglycemic hospitalized patients. RESEARCH
      DESIGN AND METHODS: A total of 180 hospitalized patients with type 2 diabetes
      received either glulisine (n = 88) or regular insulin (n = 92) before each meal
      in combination with insulin glargine at bedtime in a randomized double-blind
      fashion. All previous diabetes medications were discontinued if applicable. Doses
      of insulin were adjusted to obtain target blood glucose concentrations of <130
      mg/dl before meals and at bedtime while avoiding hypoglycemia. RESULTS: Overall
      mean blood glucose concentrations were ~ 8 mg/dl lower in the glulisine group
      than in the regular insulin group (152.6 +/- 66.6 vs. 160.4 +/- 70.8 mg/dl; P <
      0.0002). This improvement was wholly due to ~ 22 mg/dl lower levels after 4 days
      of therapy (140 +/- 55 vs. 162 +/- 71 mg/dl; P < 0.0007); after day 4, this
      difference progressively increased such that mean blood glucose concentrations
      from day 7 onward were ~ 31 mg/dl lower in the glulisine group. The mean daily
      incidence of hypoglycemia was slightly but not significantly lower in the
      glulisine than the regular insulin group (0.10 +/- 0.02 vs. 0.14 +/- 0.03
      episode/day; P > 0.35). CONCLUSIONS: In hospitalized type 2 diabetic patients,
      glulisine may provide better glycemic control than regular insulin, especially in
      those who have a prolonged length of stay.

PMID- 20805259
TI  - Diabetic neuropathy: a cross-sectional study of the relationships among tests of
      neurophysiology.
AB  - OBJECTIVE: To determine the relationships among large, small, and autonomic fiber
      neurophysiological measures in a cross-sectional study of patients with diabetes.
      RESEARCH DESIGN AND METHODS: We assessed 130 individuals: 25 healthy subjects and
      105 subjects with diabetes. Subjects were classified by the presence or absence
      of neuropathy by physical examination. All subjects underwent autonomic testing,
      nerve conduction studies, quantitative sensory testing, and nerve-axon reflex
      vasodilation in addition to quantifiable neurological examination and symptom
      scores. Correlation and cluster analysis were used to determine relationships
      between and among different neurophysiological testing parameters. RESULTS:
      Results of neurophysiological tests were abnormal in patients with clinical
      evidence of diabetic neuropathy compared with results in healthy control subjects
      and in those without neuropathy (P < 0.01, all tests). The correlations among
      individual tests varied widely, both within (r range <0.5->0.9, NS to <0.001) and
      between test groups (r range <0.2->0.5, NS to <0.01). A two-step hierarchical
      cluster analysis revealed that neurophysiological tests do not aggregate by
      typical "small," "large," or "autonomic" nerve fiber subtypes. CONCLUSIONS: The
      modest correlation coefficients seen between the different testing modalities
      suggest that these techniques measure different neurophysiological parameters and
      are therefore not interchangeable. However, the data suggest that only a small
      number of neurophysiological tests are actually required to clinically
      differentiate individuals with neuropathy from those without. The natural
      clustering of both patients and healthy control subjects suggests that variations
      in the population will need to be considered in future studies of diabetic
      neuropathy.

PMID- 20805260
TI  - Implementing a state-based cardiovascular disease and diabetes prevention
      program.
AB  - OBJECTIVE: To evaluate weight loss and cardiometabolic risk reduction achieved
      through an adapted Diabetes Prevention Program intervention among adults at high
      risk for cardiovascular disease (CVD) and diabetes. RESEARCH DESIGN AND METHODS:
      Eight health care facilities implemented a group-based lifestyle intervention
      beginning in 2008. Participants attended 16 weekly core sessions followed by 6
      monthly after core sessions. RESULTS: A total of 1,003 participants were
      enrolled, 816 (81%) completed the core and 578 (58%) completed the after core. Of
      participants completing the core and after core, 45 and 49% achieved the 7%
      weight loss goal, respectively. There were significant improvements in blood
      pressure, fasting glucose, and LDL cholesterol among participants completing the
      intervention. CONCLUSIONS: Our findings indicate it is feasible for state
      coordinated CVD and diabetes prevention programs to achieve significant weight
      loss and improve cardiometabolic risk.

PMID- 20805261
TI  - Characteristics of beryllium exposure to small particles at a beryllium
      production facility.
AB  - Epidemiological studies have reported process-specific elevated prevalence of
      beryllium sensitization (BeS) and chronic beryllium disease (CBD) among workers.
      However, exposure-response relationships have been inconsistent, possibly due to
      incomplete characterization of many biologically relevant aspects of exposure,
      including particle size. In 1999, two surveys were conducted 3-5 months apart at
      a beryllium metal, oxide, and alloy production facility during which personal
      impactor samples (n = 198) and personal 37-mm closed-face cassette (CFC) 'total'
      samples (n = 4026) were collected. Among process areas, median particle mass
      median aerodynamic diameter ranged from 5 to 14 MUm. A large fraction of the
      beryllium aerosol was in the nonrespirable size range. Respirable beryllium
      concentrations were among the highest for oxide production [geometric mean (GM) =
      2.02 MUg m-3, geometric standard deviation (GSD) = 1.3] and pebbles plant (GM =
      1.05 MUg m-3, GSD = 2.9), areas historically associated with high risk of BeS and
      CBD. The relationship between GM 'CFC total' and GM respirable beryllium for jobs
      varied by process areas; the rank order of the jobs showed high overall
      consistency (Spearman r = 0.84), but the overall correlation was moderate
      (Pearson r = 0.43). Total beryllium concentrations varied greatly within and
      between workers among process areas; within-worker variance was larger than
      between-worker variance for most processes. A review of exposure characteristics
      among process areas revealed variation in chemical forms and solubility. Process
      areas with high risk of BeS and CBD had exposure to both soluble and insoluble
      forms of beryllium. Consideration of biologically relevant aspects of exposure
      such as beryllium particle size distribution, chemical form, and solubility will
      likely improve exposure assessment.

PMID- 20805262
TI  - World Congress on the Insulin Resistance Syndrome, 2009: the kidney, the liver,
      and insulin resistance.

PMID- 20805263
TI  - Fatigue in hemodialysis patients with and without diabetes: results from a
      randomized controlled trial of two glucose-containing dialysates.

PMID- 20805256
TI  - Antidepressant medicine use and risk of developing diabetes during the diabetes
      prevention program and diabetes prevention program outcomes study.
AB  - OBJECTIVE: To assess the association between antidepressant medicine use and risk
      of developing diabetes during the Diabetes Prevention Program (DPP) and Diabetes
      Prevention Program Outcomes Study (DPPOS). RESEARCH DESIGN AND METHODS: DPP/DPPOS
      participants were assessed for diabetes every 6 months and for antidepressant use
      every 3 months in DPP and every 6 months in DPPOS for a median 10.0-year follow
      up. RESULTS: Controlled for factors associated with diabetes risk, continuous
      antidepressant use compared with no use was associated with diabetes risk in the
      placebo (adjusted hazard ratio 2.34 [95% CI 1.32-4.15]) and lifestyle (2.48 [1.45
      4.22]) arms, but not in the metformin arm (0.55 [0.25-1.19]). CONCLUSIONS:
      Continuous antidepressant use was significantly associated with diabetes risk in
      the placebo and lifestyle arms. Measured confounders and mediators did not
      account for this association, which could represent a drug effect or reflect
      differences not assessed in this study between antidepressant users and nonusers.

PMID- 20805264
TI  - Improving type 1 diabetes after treatment of immune thrombocytopenia with
      rituximab: killing two birds with one stone.

PMID- 20805265
TI  - Utility of childhood glucose homeostasis variables in predicting adult diabetes
      and related cardiometabolic risk factors: the Bogalusa Heart Study: comment on
      Nguyen et Al.

PMID- 20805267
TI  - Eating fish and risk of type 2 diabetes: a population-based, prospective follow
      up study: comment on van Woudenbergh et Al.

PMID- 20805269
TI  - Pericardial adipose tissue, atherosclerosis, and cardiovascular disease risk
      factors: the Jackson Heart Study: comment on Liu et Al.

PMID- 20805271
TI  - Cost-effectiveness of bariatric surgery for severely obese adults with diabetes.
AB  - OBJECTIVE: To analyze the cost-effectiveness of bariatric surgery in severely
      obese (BMI >or=35 kg/m(2)) adults who have diabetes, using a validated diabetes
      cost-effectiveness model. RESEARCH DESIGN AND METHODS: We expanded the Centers
      for Disease Control and Prevention-RTI Diabetes Cost-Effectiveness Model to
      incorporate bariatric surgery. In this simulation model, bariatric surgery may
      lead to diabetes remission and reductions in other risk factors, which then lead
      to fewer diabetes complications and increased quality of life (QoL). Surgery is
      also associated with perioperative mortality and subsequent complications, and
      patients in remission may relapse to diabetes. We separately estimate the costs,
      quality-adjusted life-years (QALYs), and cost-effectiveness of gastric bypass
      surgery relative to usual diabetes care and of gastric banding surgery relative
      to usual diabetes care. We examine the cost-effectiveness of each type of surgery
      for severely obese individuals who are newly diagnosed with diabetes and for
      severely obese individuals with established diabetes. RESULTS: In all analyses,
      bariatric surgery increased QALYs and increased costs. Bypass surgery had cost
      effectiveness ratios of $7,000/QALY and $12,000/QALY for severely obese patients
      with newly diagnosed and established diabetes, respectively. Banding surgery had
      cost-effectiveness ratios of $11,000/QALY and $13,000/QALY for the respective
      groups. In sensitivity analyses, the cost-effectiveness ratios were most affected
      by assumptions about the direct gain in QoL from BMI loss following surgery.
      CONCLUSIONS: Our analysis indicates that gastric bypass and gastric banding are
      cost-effective methods of reducing mortality and diabetes complications in
      severely obese adults with diabetes.

PMID- 20805272
TI  - Cognitive function in type 1 diabetic adults with early exposure to severe
      hypoglycemia: a 16-year follow-up study.
AB  - OBJECTIVE: We assessed adulthood cognition in relation to early exposure to
      severe hypoglycemia (SH). RESEARCH DESIGN AND METHODS: Sixteen years subsequent
      to a study of cognitive function in 28 diabetic children and 28 matched control
      subjects, we reexamined the same subjects with a 96% participation rate. Diabetic
      subjects were classified as with (n = 9) or without (n = 18) early (<or=10 years
      of age) SH, which was defined as convulsions or loss of consciousness. RESULTS:
      Overall, cognitive scores were 0.9 SDs lower in subjects with early SH compared
      with subjects without early SH (P = 0.003). The two diabetic groups particularly
      differed with respect to problem solving, verbal function, and psychomotor
      efficiency. Earlier age at first incident of SH was associated with poorer
      cognition (P for trend = 0.001). CONCLUSIONS: The findings suggest that early
      exposure to SH may have lasting and clinically relevant effects on cognition.

PMID- 20805273
TI  - Disparate effects of atorvastatin compared with simvastatin on C-reactive protein
      concentrations in patients with type 2 diabetes.
AB  - OBJECTIVE: Reduction in LDL and high sensitivity (hs) C-reactive protein (CRP)
      are independent indicators of successful cardiovascular risk reduction with
      statins. This study compared the effect of equivalent LDL-lowering doses of
      simvastatin and atorvastatin on hsCRP in type 2 diabetic patients. RESEARCH
      DESIGN AND METHODS: A crossover study of 26 patients with type 2 diabetes taking
      either 40 mg simvastatin or 10 mg atorvastatin was undertaken. After 3 months on
      one statin, lipids and hsCRP were measured on 10 occasions over a 5-week period.
      The same procedure was then followed taking the other statin. RESULTS: LDL was
      comparable on either treatment: atorvastatin 2.2 +/- 0.2 vs. 2.1 +/- 0.3 mmol/l
      (mean +/- SD; P = 0.19). CRP of individuals taking atorvastatin was significantly
      lower than when they were taking simvastatin (median 1.08 vs. 1.47 mg/l, P =
      0.0002) and was less variable (median SD of logCRP 0.0036 vs. 0.178, P = 0.0001).
      CONCLUSIONS: Compared with simvastatin, atorvastatin reduced hsCRP and its
      variability in type 2 diabetic patients. This enhanced anti-inflammatory effect
      may prove beneficial if lower CRP is associated with improved cardiovascular
      risk.

PMID- 20805274
TI  - No protective effect of calcitriol on beta-cell function in recent-onset type 1
      diabetes: the IMDIAB XIII trial.
AB  - OBJECTIVE: We investigated whether supplementation of the active form of vitamin
      D (calcitriol) in recent-onset type 1 diabetes can protect beta-cell function
      evaluated by C-peptide and improve glycemic control assessed by A1C and insulin
      requirement. RESEARCH DESIGN AND METHODS: Thirty-four subjects (aged 11-35 years,
      median 18 years) with recent-onset type 1 diabetes and high basal C-peptide >0.25
      nmol/l were randomized in a double-blind trial to 0.25 microg/day calcitriol or
      placebo and followed-up for 2 years. RESULTS: At 6, 12, and 24 months follow-up,
      A1C and insulin requirement in the calcitriol group did not differ from the
      placebo group. C-peptide dropped significantly (P < 0.001) but similarly in both
      groups, with no significant differences at each time point. CONCLUSIONS: At the
      doses used, calcitriol is ineffective in protecting beta-cell function in
      subjects (including children) with recent-onset type 1 diabetes and high C
      peptide at diagnosis.

PMID- 20805275
TI  - Plasma 25-hydroxyvitamin D concentration and risk of incident type 2 diabetes in
      women.
AB  - OBJECTIVE: To determine the association between 25-hydroxyvitamin D (25-OHD)
      concentration and risk of incident type 2 diabetes. RESEARCH DESIGN AND METHODS:
      In a nested case-control study conducted among 608 women with newly diagnosed
      type 2 diabetes and 559 control subjects in the Nurses' Health Study, we measured
      the association between baseline plasma 25-OHD concentration and risk of incident
      diabetes. RESULTS: After adjusting for matching factors and diabetes risk
      factors, including BMI, higher levels of plasma 25-OHD were associated with a
      lower risk for type 2 diabetes. The odds ratio for incident type 2 diabetes in
      the top (median 25-OHD, 33.4 ng/ml) versus the bottom (median 25-OHD, 14.4 ng/ml)
      quartile was 0.52 (95% CI 0.33-0.83). The associations were consistent across
      subgroups of baseline BMI, age, and calcium intake. CONCLUSIONS: Plasma 25-OHD
      concentration was associated with lower risk of incident type 2 diabetes in
      women.

PMID- 20805276
TI  - Declining beta-cell function relative to insulin sensitivity with increasing
      fasting glucose levels in the nondiabetic range in children.
AB  - OBJECTIVE: In adults, higher fasting plasma glucose (FPG) levels, even within the
      normoglycemic range, are associated with increased diabetes risk. This
      investigation tested the hypothesis that beta-cell function relative to insulin
      sensitivity decreases with increasing FPG in youth. RESEARCH DESIGN AND METHODS:
      A total of 223 youth with FPG <126 mg/dl underwent evaluation of first- and
      second-phase insulin secretion during a 2-h hyperglycemic (approximately 225
      mg/dl) clamp, insulin sensitivity during a 3-h hyperinsulinemic-euglycemic clamp,
      body composition, and abdominal adiposity with dual-energy X-ray absorptiometry
      and computed tomographic scan. beta-Cell function relative to insulin sensitivity
      was calculated as the product of first-phase insulin and insulin sensitivity,
      i.e., glucose disposition index (GDI). The subjects were divided into three FPG
      categories: <or=90, >90-<100, and >or=100-<126 mg/dl. RESULTS: GDI decreased
      significantly across the three categories as FPG increased (1,086 +/- 192 vs. 814
      +/- 67 and 454 +/- 57 mg/kg/min, P = 0.002). This decline remained significant
      after adjustment for race, sex, BMI, and percent body fat or visceral fat. Within
      each FPG category, GDI declined with increasing BMI percentiles. CONCLUSIONS: The
      impairment in beta-cell function relative to insulin sensitivity is apparent even
      within the nondiabetic FPG range in children. At the current cutoff of 100 mg/dl
      for impaired fasting glucose (IFG), there is an approximately 49% decline in the
      GDI independent of obesity and race. This observation may reflect a heightened
      risk of beta-cell dysfunction and progression to diabetes in these children.
      Considering the near doubling of IFG prevalence among youth between National
      Health and Nutrition Examination Survey 1999-2000 and 2005-2006, our findings
      have important public health implications.

PMID- 20805277
TI  - Differences in maternal circulating fatty acid composition and dietary fat intake
      in women with gestational diabetes mellitus or mild gestational hyperglycemia.
AB  - OBJECTIVE: We investigated the relationship between maternal circulating fatty
      acids (FAs) and dietary FA intake in pregnant women with gestational diabetes
      mellitus (GDM; n = 49), women with hyperglycemia less severe than GDM (impaired
      glucose challenge test [GCT] non-GDM; n = 80), and normal control subjects (n =
      98). RESEARCH DESIGN AND METHODS: A case-control design was nested within a
      prospective cohort of healthy pregnant women. Fasting concentrations of serum
      total FAs (enzymatic assay) and FA composition (gas chromatography-mass
      spectrometry) were determined at entry and the third trimester. Dietary fat
      intake data were obtained from 24-h recalls. RESULTS: There was a graded increase
      among groups (control subjects, impaired GCT non-GDM, and GDM) during the third
      trimester for total FAs and individual FAs, including myristic, palmitic,
      palmitoleic, oleic, linoleic, linolenic, arachidonic, eicosapentaenoic, and
      docosahexaenoic acids (P for trend <0.03 to P < 0.001). Similar relationships
      were observed at entry in total FAs and for four FAs (myristic, palmitic,
      palmitoleic, and eicosapentaenoic acids). Women with impaired GCT non-GDM with
      BMI >or=25 kg/m(2) had the highest levels of FAs at entry, whereas women with GDM
      with BMI >or=25 kg/m(2) had the highest levels during the third trimester, and
      all grouped FAs were significantly different from lean women with impaired GCT
      non-GDM or control subjects (P < 0.05). Dietary intake of polyunsaturated FAs was
      decreased, but saturated FAs were increased in GDM compared with impaired GCT non
      GDM or control subjects (P < 0.05). CONCLUSIONS: Abnormalities in fat metabolism
      are present in both GDM and impaired GCT non-GDM women. Reducing pregravid weight
      and altering diet might prevent the associated elevation of circulating FAs.

PMID- 20805278
TI  - Latent autoimmune diabetes in adults differs genetically from classical type 1
      diabetes diagnosed after the age of 35 years.
AB  - OBJECTIVE: We studied differences between patients with latent autoimmune
      diabetes in adults (LADA), type 2 diabetes, and classical type 1 diabetes
      diagnosed after age 35 years. RESEARCH DESIGN AND METHODS: Polymorphisms in HLA
      DQB1, INS, PTPN22, and CTLA4 were genotyped in patients with LADA (n = 213), type
      1 diabetes diagnosed at >35 years of age (T1D(>35y); n = 257) or <20 years of age
      (T1D(<20y); n = 158), and type 2 diabetes. RESULTS: Although patients with LADA
      had an increased frequency of HLA-DQB1 and PTPN22 risk genotypes and alleles
      compared with type 2 diabetic subjects, the frequency was significantly lower
      compared with T1D(>35y) patients. Genotype frequencies, measures of insulin
      secretion, and metabolic traits within LADA differed according to GAD antibody
      (GADA) quartiles, but even the highest quartile differed from type 1 diabetes.
      Having two or more risk genotypes was associated with lower C-peptide
      concentrations in LADA. CONCLUSIONS: LADA patients differed genetically and
      phenotypically from both T1D(>35y) and type 2 diabetic patients in a manner
      dependent on GADA levels.

PMID- 20805279
TI  - Common genetic variation in GLP1R and insulin secretion in response to exogenous
      GLP-1 in nondiabetic subjects: a pilot study.
AB  - OBJECTIVE: Glucagon-like peptide (GLP)-1 receptor is encoded by GLP1R. The effect
      of genetic variation at this locus on the response to GLP-1 is unknown. This
      study assessed the effect of GLP1R polymorphisms on insulin secretion in response
      to hyperglycemia and to infused GLP-1 in nondiabetic subjects. RESEARCH DESIGN
      AND METHODS: Eighty-eight healthy individuals (aged 26.3 +/- 0.6 years, fasting
      glucose 4.83 +/- 0.04 mmol/l) were studied using a hyperglycemic clamp. GLP-1 was
      infused for the last 2 h of the study (0.75 pmol/kg/min over 121-180 min, 1.5
      pmol/kg/min over 181-240 min). beta-Cell responsivity (Phi(Total)) was measured
      using a C-peptide minimal model. The effect of 21 tag single nucleotide
      polymorphisms (SNPs) in GLP1R on Phi(Total) was examined. RESULTS: Two SNPs
      (rs6923761 and rs3765467) were nominally associated with altered beta-cell
      responsivity in response to GLP-1 infusion. CONCLUSIONS: Variation in GLP1R may
      alter insulin secretion in response to exogenous GLP-1. Future studies will
      determine whether such variation accounts for interindividual differences in
      response to GLP-1-based therapy.

PMID- 20805280
TI  - Diabetes, glycemic control, and new-onset heart failure in patients with stable
      coronary artery disease: data from the heart and soul study.
AB  - OBJECTIVE: Diabetes is a predictor of both coronary artery disease (CAD) and
      heart failure. It is unknown to what extent the association between diabetes and
      heart failure is influenced by other risk factors for heart failure. RESEARCH
      DESIGN AND METHODS: We evaluated the association of diabetes and A1C with
      incident heart failure in outpatients with stable CAD and no history of heart
      failure (average follow-up 4.1 years). RESULTS: Of 839 participants, 200 had
      diabetes (23.8%). Compared with patients who did not have diabetes, those with
      diabetes had an increased risk of heart failure (hazard ratio [HR] 2.17 [95% CI
      1.37-3.44]). Adjustment for risk factors for CAD (age, sex, race, smoking,
      physical inactivity, obesity, blood pressure, and LDL cholesterol), interim
      myocardial infarction, and myocardial ischemia did not alter the strength of the
      association between diabetes and heart failure. After inclusion also of other
      risk factors for heart failure (left ventricular ejection fraction, diastolic
      dysfunction, and C-reactive protein) and medication use, diabetes remained an
      independent predictor of heart failure (HR 3.34 [95% CI 1.65-6.76]; P = 0.001).
      Each 1% increase in A1C concentration was associated with a 36% increased HR of
      heart failure hospitalization (HR 1.36 [95% CI 1.17-1.58]). CONCLUSIONS: In
      patients with stable CAD who are free from heart failure at baseline, diabetes
      and glycemic control are independent risk factors for new-onset heart failure.
      The mechanisms by which diabetes and hyperglycemia lead to heart failure deserve
      further study, as the association is independent of baseline functional
      assessment of ischemia, systolic and diastolic function, and interim myocardial
      infarction.

PMID- 20805281
TI  - One-hour plasma glucose identifies insulin resistance and beta-cell dysfunction
      in individuals with normal glucose tolerance: cross-sectional data from the
      Relationship between Insulin Sensitivity and Cardiovascular Risk (RISC) study.
AB  - OBJECTIVE: Some individuals with normal glucose tolerance (NGT) exhibit a 1-h
      excursion of plasma glucose during oral glucose tolerance testing as high as that
      of individuals with impaired glucose tolerance (IGT). The aim of this study was
      to characterize their metabolic phenotype. RESEARCH DESIGN AND METHODS: A total
      of 1,205 healthy volunteers (aged 29-61 years) underwent assessment of 1) oral
      glucose tolerance and 2) insulin sensitivity (standardized euglycemic
      hyperinsulinemic clamp), as part of the Relationship between Insulin Sensitivity
      and Cardiovascular Risk (RISC) study. RESULTS: One-hour plasma glucose correlated
      better than 2-h plasma glucose with total insulin secretion (r = 0.43), beta-cell
      glucose sensitivity (r = -0.46), and beta-cell rate sensitivity (r = -0.18).
      Receiver operating characteristic analysis identified 8.95 mmol/l as the best
      cutoff value for prediction of IGT from 1-h plasma glucose (sensitivity 77% and
      specificity 80%). Participants with NGT with 1-h plasma glucose >8.95 mmol/l had
      larger waist circumference, higher BMI, lower insulin sensitivity, higher fasting
      glucose, and higher insulin secretion than their counterparts with 1-h plasma
      glucose <or=8.95 mmol/l (P < 0.001 for all comparisons). Moreover, they exhibited
      lower beta-cell glucose sensitivity (P < 0.001), beta-cell rate sensitivity (P <
      0.001), and potentiation factor (P = 0.026). When compared with conventionally
      defined IGT, they were not different in waist circumference and BMI, hepatic
      insulin extraction, beta-cell glucose sensitivity, beta-cell rate sensitivity,
      and potentiation factor but did have greater insulin sensitivity along with
      reduced basal (P = 0.001) and total insulin secretion (P = 0.002). CONCLUSIONS:
      Higher values of 1-h plasma glucose may identify an intermediate condition
      between NGT and IGT characterized by greater insulin resistance, reduced beta
      cell glucose sensitivity, and reduced beta-cell rate sensitivity.

PMID- 20805282
TI  - Disposition index, glucose effectiveness, and conversion to type 2 diabetes: the
      Insulin Resistance Atherosclerosis Study (IRAS).
AB  - OBJECTIVE: Disposition index (DI) and glucose effectiveness (S(G)) are risk
      factors for diabetes. However, the effect of DI and S(G) on future diabetes has
      not been examined in large epidemiological studies using direct measures.
      RESEARCH DESIGN AND METHODS: Insulin sensitivity index (S(I)), acute insulin
      response (AIR), and S(G) were measured in 826 participants (aged 40-69 years) in
      the Insulin Resistance Atherosclerosis Study (IRAS) by the frequently sampled
      intravenous glucose tolerance test. DI was expressed as S(I) x AIR. At the 5-year
      follow-up examination, 128 individuals (15.5%) had developed diabetes. RESULTS:
      The area under the receiver operating characteristic curve of a model with S(I)
      and AIR was similar to that of DI (0.767 vs. 0.774, P = 0.543). In a multivariate
      logistic regression model that included both DI and S(G), conversion to diabetes
      was predicted by both S(G) (odds ratio x 1 SD, 0.61 [0.47-0.80]) and DI (0.68
      [0.54-0.85]) after adjusting for demographic variables, fasting and 2-h glucose
      concentrations, family history of diabetes, and measures of obesity. Age, sex,
      race/ethnicity, glucose tolerance status, obesity, and family history of diabetes
      did not have a significant modifying impact on the relation of S(G) and DI to
      incident diabetes. CONCLUSIONS: The predictive power of DI is comparable to that
      of its components, S(I) and AIR. S(G) and DI independently predict conversion to
      diabetes similarly across race/ethnic groups, varying states of glucose
      tolerance, family history of diabetes, and obesity.

PMID- 20805283
TI  - Diabetes and heart failure in patients with coronary disease: separating markers
      from mediators.

PMID- 20805284
TI  - Genetic determinants predicting efficacy of glucose-lowering drugs?: a long way
      to go ...

PMID- 20805285
TI  - The public health implications of the cost-effectiveness of bariatric surgery for
      diabetes.

PMID- 20805286
TI  - A structural mean model to allow for noncompliance in a randomized trial
      comparing 2 active treatments.
AB  - We propose a structural mean modeling approach to obtain compliance-adjusted
      estimates for treatment effects in a randomized-controlled trial comparing 2
      active treatments. The model relates an individual's observed outcome to his or
      her counterfactual untreated outcome through the observed receipt of active
      treatments. Our proposed estimation procedure exploits baseline covariates that
      predict compliance levels on each arm. We give a closed-form estimator which
      allows for differential and unexplained selectivity (i.e. noncausal compliance
      outcome association due to unobserved confounding) as well as a nonparametric
      error distribution. In a simple linear model for a 2-arm trial, we show that the
      distinct causal parameters are identified unless covariate-specific expected
      compliance levels are proportional on both treatment arms. In the latter case,
      only a linear contrast between the 2 treatment effects is estimable and may well
      be of key interest. We demonstrate the method in a clinical trial comparing 2
      antidepressants.

PMID- 20805288
TI  - Population genetic structure of Aldabra giant tortoises.
AB  - Evolution of population structure on islands is the result of physical processes
      linked to volcanism, orogenic events, changes in sea level, as well as habitat
      variation. We assessed patterns of genetic structure in the giant tortoise of the
      Aldabra atoll, where previous ecological studies suggested population
      subdivisions as a result of landscape discontinuity due to unsuitable habitat and
      island separation. Analysis of mitochondrial DNA (mtDNA) control region sequences
      and allelic variation at 8 microsatellite loci were conducted on tortoises
      sampled in 3 locations on the 2 major islands of Aldabra. We found no variation
      in mtDNA sequences. This pattern corroborated earlier work supporting the
      occurrence of a founding event during the last interglacial period and a further
      reduction in genetic variability during historical time. On the other hand,
      significant population structure recorded at nuclear loci suggested allopatric
      divergence possibly due to geographical barriers among islands and ecological
      partitions hindering tortoise movements within islands. This is the first attempt
      to study the population genetics of Aldabra tortoises, which are now at carrying
      capacity in an isolated terrestrial ecosystem where ecological factors appear to
      have a strong influence on population dynamics.

PMID- 20805287
TI  - Neonatal behavioral changes in rats with gestational exposure to
      lipopolysaccharide: a prenatal infection model for developmental neuropsychiatric
      disorders.
AB  - Exposure to prenatal infections has been widely associated with the increased
      risk for neuropsychiatric disorders of developmental origin such as schizophrenia
      and autism. Although several behavioral and cognitive deficits have been detected
      during adulthood in rodent models of prenatal infections, early behavioral
      changes have not been well characterized. In a prenatal lipopolysaccharide (LPS)
      model, we have previously observed significant alterations in the neuronal
      cytoarchitecture during early postnatal life. In the present study, we aimed to
      investigate the potential effects of prenatal immune activation on early
      neurophenotypic presentations using a set of behavioral test battery. Female
      Sprague-Dawley rats were administered with 100 MUg/kg LPS (intraperitoneally) at
      gestational days 15 and 16. During the first postnatal week, we found no
      significant effect on maternal behavior or mother-pup interaction by this
      treatment. Also, no major changes in physical developmental milestones of pups
      were noted from postnatal (P) days P6 to P16. Importantly, prenatal LPS-exposed
      pups had a significant decrease in the number and duration of ultrasonic
      vocalization calls at P3 and P5. Prenatal LPS treatment also led to impairments
      in nest-seeking behavior and odor-stroke associative learning in neonatal rats at
      P8 and P9. At the molecular level, we detected significant decrease in the
      expression of cortical 5HT1A and 5HT1B messenger RNA at P3. These data suggest
      that prenatal exposure to an immune activator can significantly impair the
      social/communicative behavior in the neonate offspring, which may be relevant to
      childhood and premorbid abnormalities reported in autism and schizophrenia
      subjects.

PMID- 20805289
TI  - Dynamic isomiR regulation in Drosophila development.
AB  - Several recent reports have demonstrated that microRNAs (miRNAs) can exhibit
      heterogeneous ends and post-transcriptional nontemplate 3' end additions of
      uridines or adenosines. Using two small RNA deep-sequencing data sets, we show
      here that these miRNA isoforms (isomiRs) are differentially expressed across
      Drosophila melanogaster development and tissues. Specifically, we demonstrate
      that: (1) nontemplate nucleotide additions of adenosines to miRNA 3' ends are
      highly abundant in early development; (2) a subset of miRNAs with nontemplate 3'
      Us are expressed in adult tissues; and (3) the size of at least eight "mature"
      (unmodified) miRNAs varies in a life-cycle or tissue-specific manner. These
      results suggest that subtle variability in isomiR expression, which is widely
      thought to be the result of inexact Dicer processing, is regulated and
      biologically meaningful. Indeed, a subset of the miRNAs enriched for 3' adenosine
      additions during early embryonic development, including miR-282 and miR-312, show
      enrichment for target sites in developmental genes that are expressed during late
      embryogenesis, suggesting that nontemplate additions increase miRNA stability or
      strengthen miRNA:target interactions. This work suggests that isomiR expression
      is an important aspect of miRNA biology, which warrants further investigation.

PMID- 20805290
TI  - Detecting copy number variation with mated short reads.
AB  - The development of high-throughput sequencing (HTS) technologies has opened the
      door to novel methods for detecting copy number variants (CNVs) in the human
      genome. While in the past CNVs have been detected based on array CGH data, recent
      studies have shown that depth-of-coverage information from HTS technologies can
      also be used for the reliable identification of large copy-variable regions. Such
      methods, however, are hindered by sequencing biases that lead certain regions of
      the genome to be over- or undersampled, lowering their resolution and ability to
      accurately identify the exact breakpoints of the variants. In this work, we
      develop a method for CNV detection that supplements the depth-of-coverage with
      paired-end mapping information, where mate pairs mapping discordantly to the
      reference serve to indicate the presence of variation. Our algorithm, called
      CNVer, combines this information within a unified computational framework called
      the donor graph, allowing us to better mitigate the sequencing biases that cause
      uneven local coverage and accurately predict CNVs. We use CNVer to detect 4879
      CNVs in the recently described genome of a Yoruban individual. Most of the calls
      (77%) coincide with previously known variants within the Database of Genomic
      Variants, while 81% of deletion copy number variants previously known for this
      individual coincide with one of our loss calls. Furthermore, we demonstrate that
      CNVer can reconstruct the absolute copy counts of segments of the donor genome
      and evaluate the feasibility of using CNVer with low coverage datasets.

PMID- 20805292
TI  - Does switching to reduced ignition propensity cigarettes alter smoking behavior
      or exposure to tobacco smoke constituents?
AB  - INTRODUCTION: Since 2004, several jurisdictions have mandated that cigarettes
      show reduced ignition propensity (RIP) in laboratory testing. RIP cigarettes may
      limit fires caused by smoldering cigarettes, reducing fire-related deaths and
      injury. However, some evidence suggests that RIP cigarettes emit more carbon
      monoxide and polycyclic aromatic hydrocarbons, and smokers may alter their
      smoking patterns in response to RIP cigarettes. Both of these could increase
      smokers' exposures to harmful constituents in cigarettes. METHODS: An 18-day
      switching study with a comparison group was conducted in Boston, MA (N = 77), and
      Buffalo, NY (N = 83), in 2006-2007. Current daily smokers completed 4 laboratory
      visits and two 48-hr field data collections. After a 4-day baseline, Boston
      participants switched to RIP cigarettes for 14 days, whereas Buffalo participants
      smoked RIP cigarettes throughout. Outcome measures included cigarettes smoked per
      day; smoking topography; salivary cotinine; breath CO; and hydroxylated
      metabolites of pyrene, naphthalene, phenanthrene, and fluorene. Because the
      groups differed demographically, analyses adjusted for race, age, and sex.
      RESULTS: We observed no significant changes in smoking topography or CO exposure
      among participants who switched to RIP cigarettes. Cigarette use decreased
      significantly in the switched group (37.7 cigarettes/48 hr vs. 32.6 cigarettes/48
      hr, p = .031), while hydroxyphenanthrenes increased significantly (555 ng/g
      creatinine vs. 669 ng/g creatinine, p = .007). No other biomarkers were
      significantly affected. DISCUSSION: Small increases in exposure to phenanthrene
      among smokers who switched to RIP versions were observed, while other exposures
      and smoking topography were not significantly affected. Toxicological
      implications of these findings are unclear. These findings should be weighed
      against the potential public health benefits of adopting RIP design standards for
      cigarette products.

PMID- 20805291
TI  - Diversity in antioxidant response enzymes in progressive stages of human
      nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD), which occurs in approximately 17 to 40%
      of Americans, encompasses progressive stages of liver damage ranging from
      steatosis to nonalcoholic steatohepatitis (NASH). Inflammation and oxidative
      stress are known characteristics of NAFLD; however, the precise mechanisms
      occurring during disease progression remain unclear. The purpose of the current
      study was to determine whether the expression or function of enzymes involved in
      the antioxidant response, NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione
      transferase (GST), and glutamate cysteine ligase, are altered in the progression
      of human NAFLD. Human livers staged as normal, steatotic, NASH (fatty), and NASH
      (not fatty) were obtained from the Liver Tissue Cell Distribution System. NQO1
      mRNA, protein, and activity tended to increase with disease progression. mRNA
      levels of the GST isoforms A1, A2, A4, M3, and P1 increased with NAFLD
      progression. Likewise, GST A and P protein increased with progression; however,
      GST M protein levels tended to decrease. Of interest, total GST activity toward
      the substrate 1-chloro-2,4-dinitrobenzene decreased with NAFLD progression. GSH
      synthesis does not seem to be significantly dysregulated in NAFLD progression;
      however, the GSH/oxidized glutathione redox ratio seemed to be reduced with
      disease severity, indicating the presence of oxidative stress and depletion of
      GSH throughout progression of NAFLD. Malondialdehyde concentrations were
      significantly increased with disease progression, further indicating the presence
      of oxidative stress. Nuclear immunohistochemical staining of nuclear factor E2
      related factor 2 (Nrf2), an indicator of activation of the transcription factor,
      was evident in all stages of NAFLD. The current data suggest that Nrf2 activation
      occurs in response to disease progression followed by induction of specific Nrf2
      targets, whereas functionality of specific antioxidant defense enzymes seems to
      be impaired as NAFLD progresses.

PMID- 20805293
TI  - Residual tobacco smoke in used cars: futile efforts and persistent pollutants.
AB  - INTRODUCTION: Smoking cigarettes in the enclosed environment of a car leads to
      the contamination of a car's microenvironment with residual tobacco smoke
      pollution (TSP). METHODS: Surface wipe, air, and dust samples were collected in
      used cars sold by nonsmokers (n = 40) and smokers (n = 87) and analyzed for
      nicotine. Primary drivers were interviewed about smoking behavior and
      restrictions, and car interiors were inspected to investigate (a) differences in
      car dustiness, signs of past smoking, ventilation use, mileage, and passenger
      cabin volume among nonsmokers and smokers with and without in-car smoking bans
      and (b) factors that contribute to the contamination of cars with residual TSP,
      such as ventilation use, cleaning behaviors, signs of past smoking, and holding
      the cigarette near/outside the car window while smoking. RESULTS: Smokers
      reported using air conditioning less (p < .05) and driving with windows down more
      often than nonsmokers (p = .05); their cars were also dustier (p < .01) and
      exhibited more ash and burn marks than nonsmokers' cars (p < .001). Number of
      cigarettes smoked by the primary driver was the strongest predictor of residual
      TSP indicators (R(2) = .10 - .16, p = .001). This relationship was neither
      mediated by ash or burn marks nor moderated by efforts to remove residual TSP
      from the vehicle (i.e., cleaning, ventilation) or attempts to prevent tobacco
      smoke pollutants from adsorbing while smoking (e.g., holding the cigarette
      near/outside window). DISCUSSION: Findings suggest that smokers can prevent their
      cars from becoming contaminated with residual TSP by reducing or ceasing smoking;
      however, commonly used cleaning and ventilation methods did not successfully
      decrease contamination levels. Disclosure requirements and smoke-free
      certifications could help protect buyers of used cars and empower them to request
      nonsmoking environments or a discount on cars that have been smoked in
      previously.

PMID- 20805294
TI  - Bosentan treatment of digital ulcers related to systemic sclerosis: results from
      the RAPIDS-2 randomised, double-blind, placebo-controlled trial.
AB  - OBJECTIVES: Ischaemic digital ulcers (DUs) are common in patients with systemic
      sclerosis (SSc) and are a cause of disease-related morbidity. In an earlier
      trial, treatment with bosentan, an oral endothelin receptor antagonist, reduced
      the occurrence of new DUs by 48%. The present study (RAPIDS-2, for 'RAndomized,
      double-blind, Placebo-controlled study with bosentan on healing and prevention of
      Ischemic Digital ulcers in patients with systemic Sclerosis') was conducted to
      more fully evaluate the effects of bosentan treatment on DUs associated with SSc.
      METHODS: This double-blind, placebo-controlled trial conducted at 41 centres in
      Europe and North America randomised 188 patients with SSc with at least 1 active
      DU ('cardinal ulcer') to bosentan 62.5 mg twice daily for 4 weeks and 125 mg
      twice daily thereafter for 20 weeks (n=98) or matching placebo (n=90; total 24
      weeks). The two primary end points were the number of new DUs and the time to
      healing of the cardinal ulcer. Secondary end points included pain, disability and
      safety. RESULTS: Over 24 weeks, bosentan treatment was associated with a 30%
      reduction in the number of new DUs compared with placebo (mean +/- standard
      error: 1.9+/-0.2 vs 2.7+/-0.3 new ulcers; p=0.04). This effect was greater in
      patients who entered the trial with more DUs. There was no difference between
      treatments in healing rate of the cardinal ulcer or secondary end points of pain
      and disability. Peripheral oedema and elevated aminotransferases were associated
      with bosentan treatment. CONCLUSIONS: Bosentan treatment reduced the occurrence
      of new DUs in patients with SSc but had no effect on DU healing. Bosentan was
      well tolerated and may be a useful adjunct in the management of patients with SSc
      with recurrent DUs.

PMID- 20805295
TI  - Pulmonary outcome in juvenile dermatomyositis: a case-control study.
AB  - OBJECTIVES: To compare pulmonary function in patients with juvenile
      dermatomyositis (JDM) with that of matched controls; and to examine associations
      between pulmonary function impairment, high-resolution CT (HRCT) abnormalities
      and other disease variables in patients with JDM. METHODS: A total of 59 patients
      with JDM clinically examined a median 16.8 years (range 2-38 years) after disease
      onset were compared with 59 age-matched and sex-matched controls. Pulmonary
      function tests included spirometry, diffusing capacity for carbon monoxide (DLCO)
      and body plethysmography. In patients with JDM, HRCT scans were performed and
      cumulative organ damage and patient-reported health status assessed. RESULTS:
      Patients with JDM had lower total lung capacity (TLC) and DLCO compared to
      controls (p=0.003 and <0.001, respectively). A low TLC was found in 26% of
      patients versus 9% of controls (p=0.026), and a low DLCO in 49% of patients
      versus 9% of controls (p<0.001). HRCT abnormalities were found in 37% of
      patients, and included interstitial lung disease (ILD) (14%), chest wall
      calcinosis (14%) and airway disease (15%). Three patients were diagnosed as
      having ILD prior to the follow-up visit. A low TLC was more often found in
      patients with than without abnormal HRCT (50% vs 12%, p=0.002). HRCT abnormality
      correlated with cumulative organ damage (r(s)=0.346, p=0.008) and patient
      reported health status at follow-up (p<0.005). CONCLUSIONS: Patients with JDM had
      smaller lung volumes than controls; a restrictive ventilatory defect was found in
      26% and HRCT abnormality in 37% of the patients, and these findings were
      associated. Although mostly subclinical, the relatively high frequency of
      pulmonary involvement highlights the systemic nature of JDM.

PMID- 20805296
TI  - Genetic variants within the MAP kinase signalling network and anti-TNF treatment
      response in rheumatoid arthritis patients.
AB  - BACKGROUND: Rheumatoid arthritis (RA) does not always respond to available
      treatments, including tumour necrosis factor (TNF) antagonists. A study was
      undertaken to investigate whether genetic variation within genes, encoding
      proteins in the p38 signalling network, contributes to the variable response to
      TNF antagonists. METHODS: 1102 UK Caucasian patients with RA receiving anti-TNF
      therapy (infliximab, adalimumab and etanercept) were genotyped for 38 pairwise
      tagging single nucleotide polymorphisms (SNPs) spanning 12 candidate genes from
      the p38 network. Regression analyses were performed to test association between
      genotype and treatment response at 6 months using both absolute change in DAS28
      (Disease Activity Score across 28 joints) and European League Against Rheumatism
      (EULAR) improvement criteria. Stratified analyses were performed to investigate
      association with individual therapies. RESULTS: Seven SNPs, in five genes, were
      associated with improvement in DAS28 at 6 months at a nominal 0.1 significance
      level, jointly explaining 3% of variance in outcome in a model adjusting for
      other predictors. These encoded proteins both upstream (MKK6) and downstream
      (MAPKAPK2, MSK1, MSK2) of p38, and MAPK14, the p38-alpha isoform of p38 MAPK. One
      SNP (rs2716191 in MAP2K6) was associated with EULAR response at the 0.1 level.
      SNPs generally showed greater correlation with response to infliximab and
      adalimumab, but not to etanercept. CONCLUSIONS: More SNPs than would be expected
      by chance, mapping to the p38 signalling network, showed association with the
      anti-TNF response as a whole, and particularly with the response to infliximab
      and adalimumab. Validation of these findings in independent cohorts is warranted.

PMID- 20805297
TI  - Effect of intra-articular corticosteroid injections and inflammation on
      periarticular and generalised bone loss in early rheumatoid arthritis.
AB  - OBJECTIVES: To explore the effect of intra-articular corticosteroid (IAST)
      injections on bone mineral density (BMD) in the hand and at the
      metacarpophalangeal (MCP) joints in early rheumatoid arthritis (RA). METHODS: In
      the first 3 months of the study, 19 patients with RA received methotrexate (MTX)
      alone and 21 received MTX and IAST injections into clinically inflamed joints. In
      the following 9 months, all patients received MTX+IAST. BMD was assessed at the
      hand and periarticular regions at MCP joints 2-5 at baseline, 3 and 12 months.
      RESULTS: In the first 3 months a numerically lower percentage rate of bone loss
      was seen in MTX+IAST-treated patients compared with MTX-treated patients. This
      observation was more pronounced at the MCP periarticular regions (eg, partial
      proximal phalanges: digit 2, -0.45% vs -2.69%, p=0.045; digit 3, -0.34% vs 
      3.32%, p=0.003; digit 4, -0.39% vs -2.57%, p=0.14; digit 5, -0.59% vs -2.70%,
      p=0.24) than for the whole hand (-1.53% vs -2.42%, p=0.32). In the 3-12-month
      period, only minor non-statistically significant differences were seen between
      the two groups. CONCLUSION: IAST given over 3 months protects against
      periarticular bone loss in inflamed finger joints in RA. These data emphasise the
      importance of suppressing inflammation in patients with active RA to maintain
      bone health.

PMID- 20805298
TI  - GDF5 deficiency in mice is associated with instability-driven joint damage, gait
      and subchondral bone changes.
AB  - OBJECTIVES: A functional polymorphism leading to reduced levels of growth and
      differentiation factor 5 (GDF5) was recently identified as a susceptibility
      factor for osteoarthritis. The authors studied the potential mechanisms of GDF5
      involvement in osteoarthritis using haploinsufficient Gdf5(Bp-J/+) mice. METHODS:
      Gdf5(Bp-J/+) mice were challenged in the collagenase-induced arthritis model, the
      medial meniscus destabilisation model, the papain-induced arthritis model and a
      treadmill running model. Bone density and subchondral bone parameters were
      determined using dual energy x-ray absorptiometry and peripheral quantitative CT.
      Additional in-vitro and ex-vivo analyses studied cartilage metabolism, gait and
      collagen characteristics. RESULTS: Gdf5(Bp-J/+) mice appeared phenotypically
      normal. No difference in osteoarthritis severity was found in the different
      models, with the exception of increased synovial hyperplasia in the joints of
      Gdf5(Bp-J/+) mice in the treadmill model. However, in the collagenase-induced
      model severe joint damage was found in the contralateral joints of Gdf5(Bp-J/+)
      mice. Gait analysis demonstrated an aberrant walking pattern in Gdf5(Bp-J/+)
      mice. In addition, Gdf5(Bp-J/+) mice have a decreased subchondral bone density
      and a distorted arrangement of collagen fibres in bone. CONCLUSIONS: These data
      suggest that decreased GDF5 levels in mice can contribute to osteoarthritis
      development by different mechanisms including altered loading and subchondral
      bone changes. This highlights the importance of the joint as an organ with
      different tissues involved in joint disease.

PMID- 20805299
TI  - Phase I safety, pharmacokinetics, and inhibition of SRC activity study of
      saracatinib in patients with solid tumors.
AB  - PURPOSE: This dose-escalation study evaluated the safety, tolerability, and
      pharmacokinetics (PK) of the oral Src inhibitor saracatinib (AZD0530) in patients
      with advanced solid malignancies. Tumor biopsy samples were taken to investigate
      the effect of saracatinib on Src activity in tumors. EXPERIMENTAL DESIGN: Part A
      of the study followed a multiple-ascending dose design to establish the maximum
      tolerated dose (MTD) of saracatinib. Part B was a randomized, parallel-group,
      cohort-expansion phase to further assess tolerated doses. Safety, tolerability,
      and Src activity (immunohistochemistry and lysate-based methodologies) were
      assessed after 21 days of once-daily oral dosing. PK was assessed after single
      and multiple dosing. RESULTS: In part A, 30 patients received once-daily
      saracatinib at doses of 60 to 250 mg; the MTD was established as 175 mg. In part
      B, 51 patients were randomized to receive 50 mg (n = 16), 125 mg (n = 16), or 175
      mg (n = 19) of saracatinib. The most common grade >=3 events considered to be
      treatment related were anemia, diarrhea, and asthenia. Tumor Src activity was
      reduced following saracatinib treatment. The area under the concentration-time
      curve and C(max) of saracatinib increased with increasing dose. Saracatinib
      accumulated 4- to 5-fold on once-daily dosing to reach steady-state exposure
      after 10 to 17 days of dosing. The half-life was ~40 hours. CONCLUSIONS:
      Saracatinib was well tolerated in patients with advanced solid malignancies. A
      reduction in tumor Src activity was observed. PK data show that saracatinib is
      suitable for once-daily oral dosing. Based on this study, the recommended dose
      for the phase II studies was chosen to be 175 mg/d.

PMID- 20805300
TI  - Engineered thio-trastuzumab-DM1 conjugate with an improved therapeutic index to
      target human epidermal growth factor receptor 2-positive breast cancer.
AB  - PURPOSE: Antibody drug conjugates (ADCs) combine the ideal properties of both
      antibodies and cytotoxic drugs by targeting potent drugs to the antigen
      expressing tumor cells, thereby enhancing their antitumor activity. Successful
      ADC development for a given target antigen depends on optimization of antibody
      selection, linker stability, cytotoxic drug potency, and mode of linker-drug
      conjugation to the antibody. Here, we systematically examined the in vitro
      potency as well as in vivo preclinical efficacy and safety profiles of a
      heterogeneous preparation of conventional trastuzumab-mcc-DM1 (TMAb-mcc-DM1) ADC
      with that of a homogeneous engineered thio-trastuzumab-mpeo-DM1 (thioTMAb-mpeo
      DM1) conjugate. EXPERIMENTAL DESIGN AND RESULTS: To generate thioTMAb-mpeo-DM1,
      one drug maytansinoid 1 (DM1) molecule was conjugated to an engineered cysteine
      residue at Ala114 (Kabat numbering) on each trastuzumab-heavy chain, resulting in
      two DM1 molecules per antibody. ThioTMAb-mpeo-DM1 retained similar in vitro anti
      cell proliferation activity and human epidermal growth factor receptor 2 (HER2)
      binding properties to that of the conventional ADC. Furthermore, it showed
      improved efficacy over the conventional ADC at DM1-equivalent doses (MUg/m(2))
      and retained efficacy at equivalent antibody doses (mg/kg). An improved safety
      profile of >2-fold was observed in a short-term target-independent rat safety
      study. In cynomolgus monkey safety studies, thioTMAb-mpeo-DM1 was tolerated at
      higher antibody doses (up to 48 mg/kg or 6,000 MUg DM1/m(2)) compared with the
      conventional ADC that had dose-limiting toxicity at 30 mg/kg (6,000 MUg
      DM1/m(2)). CONCLUSIONS: The engineered thioTMAb-mpeo-DM1 with broadened
      therapeutic index represents a promising antibody drug conjugate for future
      clinical development of HER2-positive targeted breast cancer therapies.

PMID- 20805301
TI  - Colorectal cancer-specific cytochrome P450 2W1: intracellular localization,
      glycosylation, and catalytic activity.
AB  - Cytochrome P450 2W1 (CYP2W1) is expressed at high levels in colorectal cancer
      cells. Moreover, we have shown previously that a higher tumor expression is
      associated with less survival. In this study, we characterize post-translational
      modification, inverted endoplasmic reticulum (ER) topology, and catalytic
      activity of CYP2W1. The analysis of colorectal normal and cancer tissues and
      CYP2W1 overexpressing human embryonic kidney (HEK) 293 cells showed that a
      fraction of CYP2W1 is modified by N-glycosylation. Bioinformatic analysis
      identified Asn177 as the only possible glycosylation site of CYP2W1, which was
      supported by the inability of an N177A mutant to be glycosylated in HEK 293
      cells. Analysis of the membrane topology indicated that unlike other cytochromes
      P450, CYP2W1 in HEK 293-transfected cells and in nontransfected Caco2TC7 and
      HepG2 cells is oriented toward the lumen of the ER, a topology making CYP2W1
      available to the ER glycosylation machinery. Immunofluorescence microscopy and
      cell surface biotinylation experiments revealed approximately 8% of the CYP2W1 on
      the cell surface. Despite the reverse orientation of CYP2W1 in the ER membrane,
      apparently making functional interactions with NADPH-cytochrome P450 reductase
      impossible, CYP2W1 in HEK 293 cells was active in the metabolism of indoline
      substrates and was able to activate aflatoxin B1 into cytotoxic products. The
      study identifies for the first time a cytochrome P450 enzyme with a luminal ER
      orientation and still retaining catalytic activity. Together, these results
      suggest the possibility of using CYP2W1 as a drug target in the treatment of
      colon cancer using antibodies and/or specific CYP2W1 activated prodrugs.

PMID- 20805302
TI  - microRNA signature and expression of Dicer and Drosha can predict prognosis and
      delineate risk groups in neuroblastoma.
AB  - Neuroblastoma is a common childhood tumor and accounts for 15% of pediatric
      cancer deaths. To investigate the microRNA (miRNA) profile and role of Dicer and
      Drosha in neuroblastoma, we assessed the expression of 162 human miRNAs, Dicer
      and Drosha in 66 neuroblastoma tumors by using real-time PCR methods. We found
      global downregulation of miRNA expression in advanced neuroblastoma and
      identified 27 miRNAs that can clearly distinguish low- from high-risk patients.
      Furthermore, expression levels of Dicer or Drosha were low in high-risk
      neuroblastoma tumors, which accounted for global downregulation of miRNAs in
      advanced disease and correlated with poor outcome. Notably, for patients with non
      MYCN-amplified tumors, low expression of Dicer can serve as a significant and
      independent predictor of poor outcome (hazard ratio, 9.6; P = 0.045; n = 52).
      Using plausible neural networks to select a combination of 15 biomarkers that
      consist of 12 miRNAs' signature, expression levels of Dicer and Drosha, and age
      at diagnosis, we were able to segregate all patients into four distinct patterns
      that were highly predictive of clinical outcome. In vitro studies also showed
      that knockdown of either Dicer or Drosha promoted the growth of neuroblastoma
      cell lines. Our results reveal that a combination of 15 biomarkers can delineate
      risk groups of neuroblastoma and serve as a powerful predictor of clinical
      outcome. Moreover, our findings of growth promotion by silencing Dicer/Drosha
      implied their potential use as therapeutic targets for neuroblastoma.

PMID- 20805303
TI  - The novel pyrrolidine nor-lobelane analog UKCP-110 [cis-2,5-di-(2-phenethyl)
      pyrrolidine hydrochloride] inhibits VMAT2 function, methamphetamine-evoked
      dopamine release, and methamphetamine self-administration in rats.
AB  - Both lobeline and lobelane attenuate methamphetamine self-administration in rats
      by decreasing methamphetamine-induced dopamine release via interaction with
      vesicular monoamine transporter-2 (VMAT2). A novel derivative of nor-lobelane,
      cis-2,5-di-(2-phenethyl)-pyrrolidine hydrochloride (UKCP-110), and its trans
      isomers, (2R,5R)-trans-di-(2-phenethyl)-pyrrolidine hydrochloride (UKCP-111) and
      (2S,5S)-trans-di-(2-phenethyl)-pyrrolidine hydrochloride (UKCP-112), were
      evaluated for inhibition of [(3)H]dihydrotetrabenazine binding and [(3)H]dopamine
      uptake by using a rat synaptic vesicle preparation to assess VMAT2 interaction.
      Compounds were evaluated for inhibition of [(3)H]nicotine and
      [(3)H]methyllycaconitine binding to assess interaction with the major nicotinic
      receptor subtypes. In addition, compounds were evaluated for inhibition of
      methamphetamine-evoked endogenous dopamine release by using striatal slices. The
      most promising compound, UKCP-110, was evaluated for its ability to decrease
      methamphetamine self-administration and methamphetamine discriminative stimulus
      cues and for its effect on food-maintained operant responding. UKCP-110, UKCP
      111, and UKCP-112 inhibited [(3)H]dihydrotetrabenazine binding (K(i) = 2.66 +/-
      0.37, 1.05 +/- 0.10, and 3.80 +/- 0.31 MUM, respectively) and had high potency
      inhibiting [(3)H]dopamine uptake (K(i) = 0.028 +/- 0.001, 0.046 +/- 0.008, 0.043
      +/- 0.004 MUM, respectively), but lacked affinity at nicotinic receptors.
      Although the trans-isomers did not alter methamphetamine-evoked dopamine release,
      UKCP-110 inhibited (IC(50) = 1.8 +/- 0.2 MUM; I(max) = 67.18 +/- 6.11 MUM)
      methamphetamine-evoked dopamine release. At high concentrations, UKCP-110 also
      increased extracellular dihydroxyphenylacetic acid. It is noteworthy that UKCP
      110 decreased the number of methamphetamine self-infusions, while having no
      effect on food-reinforced behavior or the methamphetamine stimulus cue. Thus,
      UKCP-110 represents a new lead in the development of novel pharmacotherapies for
      the treatment of methamphetamine abuse.

PMID- 20805304
TI  - Identification and characterization of dual inhibitors for phospholipid transfer
      protein and microsomal triglyceride transfer protein.
AB  - Phospholipid transfer protein (PLTP) plays an important role in atherogenesis and
      lipoprotein metabolism. PLTP exerts its functions intracellularly and
      extracellularly. Both PLTP and microsomal triglyceride transfer protein (MTP)
      have been shown to regulate the secretion of apolipoprotein B (apoB) in
      hepatocytes. We have previously reported the characterization of inhibitors that
      selectively inhibit PLTP activity and reduce apoB secretion in hepatocytes. In
      the present study, we identified more compounds that inhibit both PLTP and MTP
      activity to various extents. These dual inhibitors are structurally different
      from the PLTP-selective inhibitors. In human hepatoma cell lines, dual inhibitors
      seem to be more effective in reducing apoB secretion than selective PLTP or MTP
      inhibitors. Furthermore, the dual inhibitors markedly reduced triglyceride
      secretion from hepatocytes. In the absence of PLTP, the dual inhibitors can
      further reduce apoB secretion, whereas selective PLTP inhibitors had no effect.
      We conclude that MTP and PLTP may work coordinately in the process of hepatic
      apoB assembly and secretion. To avoid liver toxicity mediated by MTP inhibition,
      selective PLTP inhibitors should be pursued.

PMID- 20805305
TI  - Endogenous luminal surface adenosine signaling regulates duodenal bicarbonate
      secretion in rats.
AB  - Luminal ATP increases duodenal bicarbonate secretion (DBS) via brush border P2Y
      receptors. Because ATP is sequentially dephosphorylated to adenosine (ADO) and
      the brush border highly expresses adenosine deaminase (ADA), we hypothesized that
      luminal [ADO] regulators and sensors, including P1 receptors, ADA, and nucleoside
      transporters (NTs) regulate DBS. We measured DBS with pH and CO(2) electrodes,
      perfusing ADO +/- adenosine receptor agonists or antagonists or the cystic
      fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTR(inh)-172 on
      DBS. Furthermore, we examined the effect of inhibitors of ADA or NT on DBS.
      Perfusion of AMP or ADO (0.1 mM) uniformly increased DBS, whereas inosine had no
      effect. The A(1/2) receptor agonist 5'-(N-ethylcarboxamido)-adenosine (0.1 mM)
      increased DBS, whereas ADO-augmented DBS was inhibited by the potent A(2B)
      receptor antagonist N-(4-cyanophenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3
      dipropyl-1H-purin-8-yl)phenoxy]-acetamide (MRS1754) (10 MUM). Other selective
      adenosine receptor agonists or antagonists had no effect. The A(2B) receptor was
      immunolocalized to the brush border membrane of duodenal villi, whereas the A(2A)
      receptor was immunolocalized primarily to the vascular endothelium. Furthermore,
      ADO-induced DBS was enhanced by 2'-deoxycoformycin (1 MUM) and formycin B (0.1
      mM), but not by S-(4-nitrobenzyl)-6-thioinosine (0.1 mM), and it was abolished by
      CFTR(inh)-172 pretreatment (1 mg/kg i.p). Moreover, ATP (0.1 mM)-induced DBS was
      partially reduced by (1R,2S,4S,5S)-4-2-iodo-6-(methylamino)-9H-purin-9-yl]-2
      (phosphonooxy)bicyclo[3.1.0]hexane-1-methanol dihydrogen phosphate ester
      tetraammonium salt (MRS2500) or 8-[4-[4-(4-chlorophenzyl)piperazide-1
      sulfonyl)phenyl]]-1-propylxanthine (PSB603) and abolished by both, suggesting
      that ATP is sequentially degraded to ADO. Luminal ADO stimulates DBS via A(2B)
      receptors and CFTR. ATP release, ecto-phosphohydrolases, ADA, and concentrative
      NT may coordinately regulate luminal surface ADO concentration to modulate ADO-P1
      receptor signaling in rat duodenum.

PMID- 20805307
TI  - An unusual elevated lesion of the oesophagus.

PMID- 20805306
TI  - Bronchodilator activity of (3R)-3-[[[(3-fluorophenyl)[(3,4,5
      trifluorophenyl)methyl]amino] carbonyl]oxy]-1-[2-oxo-2-(2-thienyl)ethyl]-1
      azoniabicyclo[2.2.2]octane bromide (CHF5407), a potent, long-acting, and
      selective muscarinic M3 receptor antagonist.
AB  - The novel quaternary ammonium salt (3R)-3-[[[(3-fluorophenyl)[(3,4,5
      trifluorophenyl)methyl]amino]carbonyl]oxy]-1-[2-oxo-2-(2-thienyl)ethyl]-1
      azoniabicyclo[2.2.2]octane bromide (CHF5407) showed subnanomolar affinities for
      human muscarinic M1 (hM1), M2 (hM2), and M3 (hM3) receptors and dissociated very
      slowly from hM3 receptors (t(&frac12;) = 166 min) with a large part of the
      receptorial complex (54%) remaining undissociated at 32 h from radioligand
      washout. In contrast, [(3)H]CHF5407 dissociated quickly from hM2 receptors
      (t(&frac12;) = 31 min), whereas [(3)H]tiotropium dissociated slowly from both hM3
      (t(&frac12;) = 163 min) and hM2 receptor (t(&frac12;) = 297 min). In the guinea
      pig isolated trachea and human isolated bronchus, CHF5407 produced a potent
      (pIC(50) = 9.0-9.6) and long-lasting (up to 24 h) inhibition of M3 receptor
      mediated contractile responses to carbachol. In the guinea pig electrically
      driven left atrium, the M2 receptor-mediated inhibitory response to carbachol was
      recovered more quickly in CHF5407-pretreated than in tiotropium-pretreated
      preparations. CHF5407, administered intratracheally to anesthetized guinea pigs,
      potently inhibited acetylcholine (Ach)-induced bronchoconstriction with an ED(50)
      value of 0.15 nmol/kg. The effect was sustained over a period of 24 h, with a
      residual 57% inhibition 48 h after antagonist administration at 1 nmol/kg. In
      conscious guinea pigs, inhaled CHF5407 inhibited Ach-induced bronchoconstriction
      for at least 24 h as did tiotropium at similar dosages. Cardiovascular parameters
      in anesthetized guinea pigs were not significantly changed by CHF5407, up to 100
      nmol/kg i.v. and up to 1000 nmol/kg i.t. In conclusion, CHF5407 shows a prolonged
      antibronchospastic activity both in vitro and in vivo, caused by a very slow
      dissociation from M3 receptors. In contrast, CHF5407 is markedly short-acting at
      M2 receptors, a behavior not shared by tiotropium.

PMID- 20805308
TI  - Perplexing plain abdominal x-ray. Radiographic opacities were due to the
      lanthanum.

PMID- 20805309
TI  - A case of dyspepsia and abdominal fullness.

PMID- 20805310
TI  - Co-stimulatory molecule CD80 expression may correlate with anti-HCV treatment
      outcome.

PMID- 20805311
TI  - The need for a consensus on the definition of remission of autoimmune
      pancreatitis after steroid treatment.

PMID- 20805312
TI  - Bleeding from oesophageal ulceration induced by endoscopic variceal ligation for
      primary prophylaxis.

PMID- 20805313
TI  - Do gliadin and tissue transglutaminase mediate PPAR downregulation in intestinal
      cells of patients with coeliac disease?

PMID- 20805314
TI  - Accurate classification of RCD requires flow cytometry.

PMID- 20805315
TI  - Effect of long-term storage in TRIzol on microarray-based gene expression
      profiling.
AB  - BACKGROUND: Although TRIzol is widely used for preservation and isolation of RNA,
      there is suspicion that prolonged sample storage in TRIzol may affect array-based
      gene expression profiling (GEP) through premature termination during reverse
      transcription. METHODS: GEP on Illumina arrays compared paired aliquots
      (cryopreserved or stored in TRIzol) of primary samples of multiple myeloma (MM)
      and acute myeloid leukemia (AML). Data were analyzed at the "probe level" (a
      single consensus value) or "bead level" (multiple measurements provided by
      individual beads). RESULTS: TRIzol storage does not affect standard probe-level
      comparisons between sample groups: different preservation methods did not
      generate differentially expressed probes (DEP) within MM or AML sample groups, or
      substantially affect the many DEPs distinguishing between these groups.
      Differences were found by gene set enrichment analysis, but these were
      dismissible because of instability with permutation of sample labels, unbalanced
      restriction to TRIzol aliquots, inconsistency between MM and AML groups, and lack
      of biological plausibility. Bead-level comparisons found many DEPs within sample
      pairs, but most (73%) were <2-fold changed. There was no consistent evidence that
      TRIzol causes premature reverse transcription termination. Instead, a subset of
      DEPs were systematically due to increased signals in TRIzol-preserved samples
      from probes near the 5' end of transcripts, suggesting better mRNA preservation
      with TRIzol. CONCLUSIONS: TRIzol preserves RNA quality well, without a
      deleterious effect on GEP. Samples stored frozen with and without TRIzol may be
      compared by GEP with only minor concern for systematic artifacts. IMPACT: The
      standard practice of prolonged sample storage in TRIzol is suitable for GEP.

PMID- 20805316
TI  - Urine cotinine underestimates exposure to the tobacco-derived lung carcinogen 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone in passive compared with active
      smokers.
AB  - OBJECTIVES: Cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are
      widely used biomarkers for tobacco-derived nicotine and the lung carcinogen 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), respectively. The discrepancy
      between cotinine levels in relation to disease risk comparing active versus
      passive smoking suggests a nonlinear tobacco smoke dose-response and/or that
      cotinine is not providing an accurate measure of exposure to the toxic
      constituents of secondhand tobacco smoke. METHODS: Cotinine and NNAL were
      measured in the urine of 373 active smokers and 228 passive smokers. RESULTS:
      Average cotinine levels were 1,155 (interquartile range, 703-2,715) for active
      smokers and 1.82 (0.45-7.33) ng/mg creatinine for passive smokers. Average NNAL
      levels were 183 (103-393) and 5.19 (2.04-11.6) pg/mg creatinine, respectively.
      NNAL/cotinine ratio in urine was significantly higher for passive smokers when
      compared with active smokers (2.85 * 10(3) versus 0.16 * 10(3), P < 0.0001).
      CONCLUSIONS: Passive smoking is associated with a much higher ratio of
      NNAL/cotinine in the urine compared with active smoking. IMPACT: Cotinine
      measurement leads to an underestimation of exposure to the carcinogen NNK from
      secondhand smoke when compared with active smoking.

PMID- 20805317
TI  - Drug-induced hemolytic anemia and thrombocytopenia associated with alterations of
      cell membrane lipids and acanthocyte formation.
AB  - CXCR3 is a chemokine receptor, upregulated upon activation of T cells and
      expressed on nearly 100% of T cells in sites of inflammation. SCH 900875 is a
      selective CXCR3 receptor antagonist. Thrombocytopenia and severe hemolytic anemia
      with acanthocytosis occurred in rats at doses of 75, 100, and 150 mg/kg/day.
      Massively enlarged spleens corresponded histologically to extramedullary
      hematopoiesis, macrophages, and hemosiderin pigment and sinus congestion.
      Phagocytosed erythrocytes and platelets were within splenic macrophages. IgG
      and/or IgM were not detected on erythrocyte and platelet membranes. Ex vivo
      increased osmotic fragility of RBCs was observed. Lipid analysis of the RBC
      membrane revealed modifications in phosphatidylcholine, overall cholesterol,
      and/or sphingomyelin. Platelets exhibited slender filiform processes on their
      plasma membranes, analogous to those of acanthocytes. The presence of similar
      morphological abnormalities in acanthocytes and platelets suggests that possibly
      similar alterations in the lipid composition of the plasma membrane have taken
      place in both cell types. This phenotype correlated with alterations in plasma
      lipids (hypercholesterolemia and low triglycerides) that occurred after SCH
      900875 administration, although other factors cannot be excluded. The increased
      cell destruction was considered triggered by alterations in the lipid profile of
      the plasma membranes of erythrocytes and platelets, as reflected morphologically.

PMID- 20805318
TI  - Lung cancer and environmental chemical exposure: a review of our current state of
      knowledge with reference to the role of hormones and hormone receptors as an
      increased risk factor for developing lung cancer in man.
AB  - Lung cancer is a dominant cause of cancer mortality. The etiology of lung cancer
      is mainly related to cigarette smoking, airborne genotoxic carcinogens, and
      arsenic, but its sex-specific incidence suggests that other mechanisms, such as
      hormones, may also be involved in the process of carcinogenesis. A number of
      agents commonly present in the living environment can have dual biological
      effects: not only are they genotoxic / carcinogenic, but they are also hormonally
      active as xenoestrogens. This dualism may explain sex-specific differences
      reported in both types and incidence of lung cancer. In a novel approach to
      investigate the complexity of lung cancer, etiology, including systems biology,
      will be used as a tool for a simultaneous interpretation of measurable
      environmental and biological parameters. Using this approach, the etiology of
      human lung cancer can be more thoroughly investigated using the available data
      from oncology and environmental health. The information gained could be applied
      in the introduction of preventive measures, in personalized medicine, and in more
      relevant legislation, which should be adjusted to reflect the current knowledge
      on the complex environmental interactions underlying this life-threatening
      disease.

PMID- 20805319
TI  - Histology atlas of the developing mouse hepatobiliary system with emphasis on
      embryonic days 9.5-18.5.
AB  - Animal model phenotyping, in utero exposure toxicity studies, and investigation
      into causes of embryonic, fetal, or perinatal deaths have required pathologists
      to recognize and diagnose developmental disorders in spontaneous and engineered
      mouse models of disease. In mammals, the liver is the main site of hematopoiesis
      during fetal development, has endocrine and exocrine functions important for
      maintaining homeostasis in fetal and adult life; and performs other functions
      including waste detoxification, production and removal of glucose, glycogen
      storage, triglyceride and fatty acid processing, and serum protein production.
      Due to its role in many critical functions, alterations in the size, morphology,
      or function(s) of the liver often lead to embryonic lethality. Many publications
      and websites describe individual aspects of hepatobiliary development at defined
      stages. However, no single resource provides a detailed histological evaluation
      of H&E-stained sections of the developing murine liver and biliary systems using
      high-magnification and high-resolution color images. The work herein provides a
      histology atlas of hepatobiliary development between embryonic days 9.5-18.5.
      Although the focus of this work is normal hepatobiliary development, common
      defects in liver development are also described as a reference for pathologists
      who may be asked to phenotype mice with congenital, inherited, or treatment
      related hepatobiliary defects. Authors' note: All digital images can be viewed
      online at https://niehsimagesepl-inc.com with the username "ToxPathLiver" and the
      password "embryolivers."

PMID- 20805320
TI  - The NuRD chromatin-remodeling complex regulates signaling and repair of DNA
      damage.
AB  - Cells respond to ionizing radiation (IR)-induced DNA double-strand breaks (DSBs)
      by orchestrating events that coordinate cell cycle progression and DNA repair.
      How cells signal and repair DSBs is not yet fully understood. A genome-wide RNA
      interference screen in Caenorhabditis elegans identified egr-1 as a factor that
      protects worm cells against IR. The human homologue of egr-1, MTA2 (metastasis
      associated protein 2), is a subunit of the nucleosome-remodeling and histone
      deacetylation (NuRD) chromatin-remodeling complex. We show that knockdown of MTA2
      and CHD4 (chromodomain helicase DNA-binding protein 4), the catalytic subunit
      (adenosine triphosphatase [ATPase]) of NuRD, leads to accumulation of spontaneous
      DNA damage and increased IR sensitivity. MTA2 and CHD4 accumulate in DSB
      containing chromatin tracks generated by laser microirradiation. Directly at
      DSBs, CHD4 stimulates RNF8/RNF168-dependent formation of ubiquitin conjugates to
      facilitate the accrual of RNF168 and BRCA1. Finally, we show that CHD4 promotes
      DSB repair and checkpoint activation in response to IR. Thus, the NuRD chromatin
      remodeling complex is a novel regulator of DNA damage responses that orchestrates
      proper signaling and repair of DSBs.

PMID- 20805321
TI  - Subgroup II PAK-mediated phosphorylation regulates Ran activity during mitosis.
AB  - Ran is an essential GTPase that controls nucleocytoplasmic transport, mitosis,
      and nuclear envelope formation. These functions are regulated by interaction of
      Ran with different partners, and by formation of a Ran-GTP gradient emanating
      from chromatin. Here, we identify a novel level of Ran regulation. We show that
      Ran is a substrate for p21-activated kinase 4 (PAK4) and that its phosphorylation
      on serine-135 increases during mitosis. The endogenous phosphorylated Ran and
      active PAK4 dynamically associate with different components of the microtubule
      spindle during mitotic progression. A GDP-bound Ran phosphomimetic mutant cannot
      undergo RCC1-mediated GDP/GTP exchange and cannot induce microtubule asters in
      mitotic Xenopus egg extracts. Conversely, phosphorylation of GTP-bound Ran
      facilitates aster nucleation. Finally, phosphorylation of Ran on serine-135
      impedes its binding to RCC1 and RanGAP1. Our study suggests that PAK4-mediated
      phosphorylation of GDP- or GTP-bound Ran regulates the assembly of Ran-dependent
      complexes on the mitotic spindle.

PMID- 20805322
TI  - The mitosis-to-interphase transition is coordinated by cross talk between the SIN
      and MOR pathways in Schizosaccharomyces pombe.
AB  - The mechanisms that regulate cytoskeletal remodeling during the transition
      between mitosis and interphase are poorly understood. In fission yeast the MOR
      pathway promotes actin polarization to cell tips in interphase, whereas the SIN
      signaling pathway drives actomyosin ring assembly and cytokinesis. We show that
      the SIN inhibits MOR signaling in mitosis by interfering with Nak1 kinase
      mediated activation of the most downstream MOR component, the NDR family kinase
      Orb6. Inactivation of the MOR may be a key function of the SIN because
      attenuation of MOR signaling rescued the cytokinetic defects of SIN mutants and
      allowed weak SIN signaling to trigger ectopic cytokinesis. Furthermore, failure
      to inhibit the MOR is toxic when the cell division apparatus is compromised.
      Together, our results reveal a mutually antagonistic relationship between the SIN
      and MOR pathways, which is important for completion of cytokinesis and
      coordination of cytoskeletal remodeling at the mitosis-to-interphase transition.

PMID- 20805323
TI  - Two distinct mechanisms target GAD67 to vesicular pathways and presynaptic
      clusters.
AB  - The inhibitory neurotransmitter gamma-amino butyric acid (GABA) is synthesized by
      two isoforms of the enzyme glutamic acid decarboxylase (GAD): GAD65 and GAD67.
      Whereas GAD67 is constitutively active and produces >90% of GABA in the central
      nervous system, GAD65 is transiently activated and augments GABA levels for rapid
      modulation of inhibitory neurotransmission. Hydrophobic lipid modifications of
      the GAD65 protein target it to Golgi membranes and synaptic vesicles in
      neuroendocrine cells. In contrast, the GAD67 protein remains hydrophilic but has
      been shown to acquire membrane association by heterodimerization with GAD65.
      Here, we identify a second mechanism that mediates robust membrane anchoring,
      axonal targeting, and presynaptic clustering of GAD67 but that is independent of
      GAD65. This mechanism is abolished by a leucine-103 to proline mutation that
      changes the conformation of the N-terminal domain but does not affect the GAD65
      dependent membrane anchoring of GAD67. Thus two distinct mechanisms target the
      constitutively active GAD67 to presynaptic clusters to facilitate accumulation of
      GABA for rapid delivery into synapses.

PMID- 20805324
TI  - The chromatin-remodeling factor CHD4 coordinates signaling and repair after DNA
      damage.
AB  - In response to ionizing radiation (IR), cells delay cell cycle progression and
      activate DNA repair. Both processes are vital for genome integrity, but the
      mechanisms involved in their coordination are not fully understood. In a mass
      spectrometry screen, we identified the adenosine triphosphate-dependent chromatin
      remodeling protein CHD4 (chromodomain helicase DNA-binding protein 4) as a factor
      that becomes transiently immobilized on chromatin after IR. Knockdown of CHD4
      triggers enhanced Cdc25A degradation and p21(Cip1) accumulation, which lead to
      more pronounced cyclin-dependent kinase inhibition and extended cell cycle delay.
      At DNA double-strand breaks, depletion of CHD4 disrupts the chromatin response at
      the level of the RNF168 ubiquitin ligase, which in turn impairs local
      ubiquitylation and BRCA1 assembly. These cell cycle and chromatin defects are
      accompanied by elevated spontaneous and IR-induced DNA breakage, reduced
      efficiency of DNA repair, and decreased clonogenic survival. Thus, CHD4 emerges
      as a novel genome caretaker and a factor that facilitates both checkpoint
      signaling and repair events after DNA damage.

PMID- 20805325
TI  - A testis-specific regulator of complex and hybrid N-glycan synthesis.
AB  - Database analyses identified 4933434I20Rik as a glycosyltransferase-like gene
      expressed mainly in testicular germ cells and regulated during spermatogenesis.
      Expression of a membrane-bound form of the protein resulted in a marked and
      specific reduction in N-acetylglucosaminyltransferase I (GlcNAcT-I) activity and
      complex and hybrid N-glycan synthesis. Thus, the novel activity was termed
      GlcNAcT-I inhibitory protein (GnT1IP). Membrane-bound GnT1IP localizes to the ER,
      the ER-Golgi intermediate compartment (ERGIC), and the cis-Golgi. Coexpression of
      membrane-anchored GnT1IP with GlcNAcT-I causes association of the two proteins,
      inactivation of GlcNAcT-I, and mislocalization of GlcNAcT-I from the medial-Golgi
      to earlier compartments. Therefore, GnT1IP is a regulator of GlcNAcT-I and
      complex and hybrid N-glycan production. Importantly, the formation of high
      mannose N-glycans resulting from inhibition of GlcNAcT-I by GnT1IP markedly
      increases the adhesion of CHO cells to TM4 Sertoli cells. Testicular germ cells
      might use GnT1IP to induce the expression of high mannose N-glycans on
      glycoproteins, thereby facilitating Sertoli-germ cell attachment at a particular
      stage of spermatogenesis.

PMID- 20805327
TI  - Arabidopsis basic leucine-zipper transcription factors TGA9 and TGA10 interact
      with floral glutaredoxins ROXY1 and ROXY2 and are redundantly required for anther
      development.
AB  - ROXY1 and ROXY2 are CC-type floral glutaredoxins with redundant functions in
      Arabidopsis (Arabidopsis thaliana) anther development. We show here that plants
      lacking the basic leucine-zipper transcription factors TGA9 and TGA10 have
      defects in male gametogenesis that are strikingly similar to those in roxy1 roxy2
      mutants. In tga9 tga10 mutants, adaxial and abaxial anther lobe development is
      differentially affected, with early steps in anther development blocked in
      adaxial lobes and later steps affected in abaxial lobes. Distinct from roxy1
      roxy2, microspore development in abaxial anther lobes proceeds to a later stage
      with the production of inviable pollen grains contained within nondehiscent
      anthers. Histological analysis shows multiple defects in the anther dehiscence
      program, including abnormal stability and lignification of the middle layer and
      defects in septum and stomium function. Compatible with these defects, TGA9 and
      TGA10 are expressed throughout early anther primordia but resolve to the middle
      and tapetum layers during meiosis of pollen mother cells. Several lines of
      evidence suggest that ROXY promotion of anther development is mediated in part by
      TGA9 and TGA10. First, TGA9 and TGA10 expression overlaps with ROXY1/2 during
      anther development. Second, TGA9/10 and ROXY1/2 operate downstream of
      SPOROCYTELESS/NOZZLE, where they positively regulate a common set of genes that
      contribute to tapetal development. Third, TGA9 and TGA10 directly interact with
      ROXY proteins in yeast and in plant cell nuclei. These findings suggest that
      activation of TGA9/10 transcription factors by ROXY-mediated modification of
      cysteine residues promotes anther development, thus broadening our understanding
      of how redox-regulated TGA factors function in plants.

PMID- 20805328
TI  - Arabidopsis calcium-dependent protein kinase CPK10 functions in abscisic acid-
      and Ca2+-mediated stomatal regulation in response to drought stress.
AB  - Plant calcium-dependent protein kinases (CDPKs) may function as calcium sensors
      and play important roles in the regulation of plant growth and development and in
      plant responses to biotic and abiotic stresses. The Arabidopsis (Arabidopsis
      thaliana) genome encodes 34 CDPKs, and most of them have not been functionally
      characterized. Here, we report the functional characterization of CPK10 in
      Arabidopsis response to drought stress. The cpk10 mutant, a T-DNA insertion
      mutant for the Arabidopsis CPK10 gene, showed a much more sensitive phenotype to
      drought stress compared with wild-type plants, while the CPK10 overexpression
      lines displayed enhanced tolerance to drought stress. Induction of stomatal
      closure and inhibition of stomatal opening by abscisic acid (ABA) and Ca(2+) were
      impaired in the cpk10 mutants. Using yeast two-hybrid methods, a heat shock
      protein, HSP1, was identified as a CPK10-interacting protein. The interaction
      between CPK10 and HSP1 was further confirmed by pull-down and bimolecular
      fluorescence complementation assays. The HSP1 knockout mutant (hsp1) plants
      showed a similar sensitive phenotype under drought stress as the cpk10 mutant
      plants and were similarly less sensitive to ABA and Ca(2+) in regulation of
      stomatal movements. Electrophysiological experiments showed that ABA and Ca(2+)
      inhibition of the inward K(+) currents in stomatal guard cells were impaired in
      the cpk10 and hsp1 mutants. All presented data demonstrate that CPK10, possibly
      by interacting with HSP1, plays important roles in ABA- and Ca(2+)-mediated
      regulation of stomatal movements.

PMID- 20805329
TI  - WAVY LEAF1, an ortholog of Arabidopsis HEN1, regulates shoot development by
      maintaining MicroRNA and trans-acting small interfering RNA accumulation in rice.
AB  - In rice (Oryza sativa), trans-acting small interfering RNA (ta-siRNA) is
      essential for shoot development, including shoot apical meristem (SAM) formation
      and leaf morphogenesis. The rice wavy leaf1 (waf1) mutant has been identified as
      an embryonic mutant resembling shoot organization1 (sho1) and sho2, homologs of a
      loss-of-function mutant of DICER-LIKE4 and a hypomorphic mutant of ARGONAUTE7,
      respectively, which both act in the ta-siRNA production pathway. About half of
      the waf1 mutants showed seedling lethality due to defects in SAM maintenance, but
      the rest survived to the reproductive phase and exhibited pleiotropic phenotypes
      in leaf morphology and floral development. Map-based cloning of WAF1 revealed
      that it encodes an RNA methyltransferase, a homolog of Arabidopsis (Arabidopsis
      thaliana) HUA ENHANCER1. The reduced accumulation of small RNAs in waf1 indicated
      that the stability of the small RNA was decreased. Despite the greatly reduced
      level of microRNAs and ta-siRNA, microarray and reverse transcription-polymerase
      chain reaction experiments revealed that the expression levels of their target
      genes were not always enhanced. A double mutant between sho and waf1 showed an
      enhanced SAM defect, suggesting that the amount and/or quality of ta-siRNA is
      crucial for SAM maintenance. Our results indicate that stabilization of small
      RNAs by WAF1 is indispensable for rice development, especially for SAM
      maintenance and leaf morphogenesis governed by the ta-siRNA pathway. In addition,
      the inconsistent relationship between the amount of small RNAs and the level of
      the target mRNA in waf1 suggest that there is a complex regulatory mechanism that
      modifies the effects of microRNA/ta-siRNA on the expression of the target gene.

PMID- 20805330
TI  - Characterization of the CpxRA regulon in Haemophilus ducreyi.
AB  - The Haemophilus ducreyi 35000HP genome encodes a homolog of the CpxRA two
      component cell envelope stress response system originally characterized in
      Escherichia coli. CpxR, the cytoplasmic response regulator, was shown previously
      to be involved in repression of the expression of the lspB-lspA2 operon (M.
      Labandeira-Rey, J. R. Mock, and E. J. Hansen, Infect. Immun. 77:3402-3411, 2009).
      In the present study, the H. ducreyi CpxR and CpxA proteins were shown to closely
      resemble those of other well-studied bacterial species. A cpxA deletion mutant
      and a CpxR-overexpressing strain were used to explore the extent of the CpxRA
      regulon. DNA microarray and real-time reverse transcriptase (RT) PCR analyses
      indicated several potential regulatory targets for the H. ducreyi CpxRA two
      component regulatory system. Electrophoretic mobility shift assays (EMSAs) were
      used to prove that H. ducreyi CpxR interacted with the promoter regions of genes
      encoding both known and putative virulence factors of H. ducreyi, including the
      lspB-lspA2 operon, the flp operon, and dsrA. Interestingly, the use of EMSAs also
      indicated that H. ducreyi CpxR did not bind to the promoter regions of several
      genes predicted to encode factors involved in the cell envelope stress response.
      Taken together, these data suggest that the CpxRA system in H. ducreyi, in
      contrast to that in E. coli, may be involved primarily in controlling expression
      of genes not involved in the cell envelope stress response.

PMID- 20805331
TI  - Interaction between pathogenic bacteria and intrauterine leukocytes triggers
      alternative molecular signaling cascades leading to labor in women.
AB  - Increased risk of preterm labor has been linked to cervicovaginal infection with
      Ureaplasma urealyticum and group B streptococci. Although various experimental
      models have been developed to study the role of amniochorion infection in preterm
      labor, they typically exclude the initial interaction between intrauterine
      leukocytes (recruited from decidual vessels into the avascular fetal membranes)
      and infecting bacteria. In this work, we ascertained whether inflammatory
      molecules secreted by bacterium-activated intrauterine leukocytes stimulate the
      amniochorion production of mediators involved in human labor. Using a two-step
      process beginning with placental circulating leukocytes as a proxy for
      intrauterine leukocytes, we found that coincubation of amniochorion explants with
      plasma from placental whole blood preincubated with group B streptococci resulted
      in a significant increase in tumor necrosis factor alpha (TNF-alpha) and matrix
      metalloproteinase 9 (MMP-9) levels in tissue. Extensive changes in the connective
      tissue arrangement and a decrease in collagen content demonstrated the
      degradation of the extracellular matrix following this treatment. In contrast,
      plasma from blood preconditioned with U. urealyticum induced a highly significant
      secretion of interleukin-1beta (IL-1beta) and prostaglandin E(2) (PGE(2)) by the
      amniochorion without changes in the extracellular matrix organization or content.
      These data demonstrate that group B streptococci induce degradation of the
      amniochorion as a result of MMP-9 production, probably via TNF-alpha, whereas U.
      urealyticum stimulates the secretion of PGE(2), probably via IL-1beta,
      potentially stimulating myometrial contraction. Our study provides novel evidence
      that the immunological cells circulating within the uterine microenvironment
      respond differentially to an infectious agent, triggering alternative molecular
      signaling pathways leading to human labor.

PMID- 20805332
TI  - Interaction of Candida albicans cell wall Als3 protein with Streptococcus
      gordonii SspB adhesin promotes development of mixed-species communities.
AB  - Candida albicans colonizes human mucosa and prosthetic surfaces associated with
      artificial joints, catheters, and dentures. In the oral cavity, C. albicans
      coexists with numerous bacterial species, and evidence suggests that bacteria may
      modulate fungal growth and biofilm formation. Streptococcus gordonii is found on
      most oral cavity surfaces and interacts with C. albicans to promote hyphal and
      biofilm formation. In this study, we investigated the role of the hyphal-wall
      protein Als3p in interactions of C. albicans with S. gordonii. Utilizing an ALS3
      deletion mutant strain, it was shown that cells were not affected in initial
      adherence to the salivary pellicle or in hyphal formation in the planktonic
      phase. However, the Als3(-) mutant was unable to form biofilms on the salivary
      pellicle or deposited S. gordonii DL1 wild-type cells, and after initial
      adherence, als3Delta/als3Delta (DeltaALS3) cells became detached concomitant with
      hyphal formation. In coaggregation assays, S. gordonii cells attached to, and
      accumulated around, hyphae formed by C. albicans wild-type cells. However,
      streptococci failed to attach to hyphae produced by the DeltaALS3 mutant.
      Saccharomyces cerevisiae S150-2B cells expressing Als3p, but not control cells,
      supported binding of S. gordonii DL1. However, S. gordonii Delta(sspA sspB) cells
      deficient in production of the surface protein adhesins SspA and SspB showed >50%
      reduced levels of binding to S. cerevisiae expressing Als3p. Lactococcus lactis
      cells expressing SspB bound avidly to S. cerevisiae expressing Als3p, but not to
      S150-2B wild-type cells. These results show that recognition of C. albicans by S.
      gordonii involves Als3 protein-SspB protein interaction, defining a novel
      mechanism in fungal-bacterial communication.

PMID- 20805333
TI  - Vascular endothelial growth factor receptor 1 contributes to Escherichia coli K1
      invasion of human brain microvascular endothelial cells through the
      phosphatidylinositol 3-kinase/Akt signaling pathway.
AB  - Escherichia coli is the most common Gram-negative organism causing neonatal
      meningitis. Previous studies demonstrated that E. coli K1 invasion of brain
      microvascular endothelial cells (BMEC) is required for penetration into the
      central nervous system, but the microbe-host interactions that are involved in
      this process remain incompletely understood. Here we report the involvement of
      vascular endothelial growth factor receptor 1 (VEGFR1) expressed on human brain
      microvascular endothelial cells (HBMEC) in E. coli K1 invasion of HBMEC. Our
      results showed that treatment of confluent HBMEC with pan-VEGFR inhibitors
      significantly inhibited E. coli K1 invasion of HBMEC. Immunofluorescence results
      indicated the colocalization of VEGFR1 with E. coli K1 during bacterial invasion
      of HBMEC. The E. coli-induced actin cytoskeleton rearrangements in HBMEC were
      blocked by VEGFR inhibitors but not by VEGFR2-specific inhibitors. The small
      interfering RNA (siRNA) knockdown of VEGFR1 in HBMEC significantly attenuated E.
      coli invasion and the concomitant actin filament rearrangement. Furthermore, we
      found an increased association of VEGFR1 with the p85 subunit of
      phosphatidylinositol 3-kinase (PI3K) in HBMEC infected with E. coli K1 and that
      E. coli K1-triggered Akt activation in HBMEC was blocked by VEGFR1 siRNA and
      VEGFR inhibitors. Taken together, our results demonstrate that VEGFR1 contributes
      to E. coli K1 invasion of HBMEC via recruitment of the PI3K/Akt signaling
      pathway.

PMID- 20805334
TI  - Role of Porphyromonas gingivalis phosphoserine phosphatase enzyme SerB in
      inflammation, immune response, and induction of alveolar bone resorption in rats.
AB  - Porphyromonas gingivalis secretes a serine phosphatase enzyme, SerB, upon contact
      with gingival epithelial cells in vitro. The SerB protein plays a critical role
      in internalization and survival of the organism in epithelial cells. SerB is also
      responsible for the inhibition of interleukin-8 (IL-8) secretion from gingival
      epithelial cells infected with P. gingivalis. This study examined the ability of
      a P. gingivalis SerB mutant to colonize the oral cavity and induce gingival
      inflammation, immune responses, and alveolar bone resorption in a rat model of
      periodontal disease. Both P. gingivalis ATCC 33277 and an isogenic DeltaSerB
      mutant colonized the oral cavities of rats during the 12-week experimental
      period. Both of the strains induced significant (P < 0.05) systemic levels of
      immunoglobulin G (IgG) and isotypes IgG1, IgG2a, and IgG2b, indicating the
      involvement of both T helper type 1 (Th1) and Th2 responses to infection. Both
      strains induced significantly (P < 0.05) higher levels of alveolar bone
      resorption in infected rats than in sham-infected control rats. However,
      horizontal and interproximal alveolar bone resorption induced by the SerB mutant
      was significantly (P < 0.05) lower than that induced by the parental strain. Rats
      infected with the DeltaSerB mutant exhibited significantly higher levels of
      apical migration of the junctional epithelium (P < 0.01) and polymorphonuclear
      neutrophil (PMN) recruitment (P < 0.001) into the gingival tissues than rats
      infected with the wild type. In conclusion, in a rat model of periodontal
      disease, the SerB phosphatase of P. gingivalis is required for maximal alveolar
      bone resorption, and in the absence of SerB, more PMNs are recruited into the
      gingival tissues.

PMID- 20805335
TI  - Translocation of Pseudomonas aeruginosa from the intestinal tract is mediated by
      the binding of ExoS to an Na,K-ATPase regulator, FXYD3.
AB  - The intestinal tract is considered the most important reservoir of Pseudomonas
      aeruginosa in intensive care units (ICUs). Gut colonization by P. aeruginosa
      underlies the development of invasive infections such as gut-derived sepsis.
      Intestinal colonization by P. aeruginosa is associated with higher ICU mortality
      rates. The translocation of endogenous P. aeruginosa from the colonized
      intestinal tract is an important pathogenic phenomenon. Here we identify
      bacterial and host proteins associated with bacterial penetration through the
      intestinal epithelial barrier. We first show by comparative genomic hybridization
      analysis that the exoS gene, encoding the type III effector protein, ExoS, was
      specifically detected in a clinical isolate that showed higher virulence in
      silkworms following midgut injection. We further show using a silkworm oral
      infection model that exoS is required both for virulence and for bacterial
      translocation from the midgut to the hemolymph. Using a bacterial two-hybrid
      screen, we show that the mammalian factor FXYD3, which colocalizes with and
      regulates the function of Na,K-ATPase, directly binds ExoS. A pulldown assay
      revealed that ExoS binds to the transmembrane domain of FXYD3, which also
      interacts with Na,K-ATPase. Na,K-ATPase controls the structure and barrier
      function of tight junctions in epithelial cells. Collectively, our results
      suggest that ExoS facilitates P. aeruginosa penetration through the intestinal
      epithelial barrier by binding to FXYD3 and thereby impairing the defense function
      of tight junctions against bacterial penetration.

PMID- 20805336
TI  - Adhesion, invasion, and agglutination mediated by two trimeric autotransporters
      in the human uropathogen Proteus mirabilis.
AB  - Fimbriae of the human uropathogen Proteus mirabilis are the only characterized
      surface proteins that contribute to its virulence by mediating adhesion and
      invasion of the uroepithelia. PMI2122 (AipA) and PMI2575 (TaaP) are annotated in
      the genome of strain HI4320 as trimeric autotransporters with "adhesin-like" and
      "agglutinating adhesin-like" properties, respectively. The C-terminal 62 amino
      acids (aa) in AipA and 76 aa in TaaP are homologous to the translocator domains
      of YadA from Yersinia enterocolitica and Hia from Haemophilus influenzae.
      Comparative protein modeling using the Hia three-dimensional structure as a
      template predicted that each of these domains would contain four antiparallel
      beta sheets and that they formed homotrimers. Recombinant AipA and TaaP were seen
      as ~28 kDa and ~78 kDa, respectively, in Escherichia coli, and each also formed
      high-molecular-weight homotrimers, thus supporting this model. E. coli
      synthesizing AipA or TaaP bound to extracellular matrix proteins with a 10- to 60
      fold-higher level of affinity than the control strain. Inactivation of aipA in P.
      mirabilis strains significantly (P < 0.01) reduced the mutants' ability to adhere
      to or invade HEK293 cell monolayers, and the functions were restored upon
      complementation. A 51-aa-long invasin region in the AipA passenger domain was
      required for this function. E. coli expressing TaaP mediated autoagglutination,
      and a taaP mutant of P. mirabilis showed significantly (P < 0.05) more reduced
      aggregation than HI4320. Gly-247 in AipA and Gly-708 in TaaP were indispensable
      for trimerization and activity. AipA and TaaP individually offered advantages to
      P. mirabilis in a murine model. This is the first report characterizing trimeric
      autotransporters in P. mirabilis as afimbrial surface adhesins and
      autoagglutinins.

PMID- 20805338
TI  - Loss of the group A Streptococcus regulator Srv decreases biofilm formation in
      vivo in an otitis media model of infection.
AB  - Group A Streptococcus (GAS) is a common causative agent of pharyngitis, but the
      role of GAS in otitis media is underappreciated. In this study, we sought to test
      the hypothesis that GAS colonizes the middle ear and establishes itself in
      localized, three-dimensional communities representative of biofilms. To test this
      hypothesis, the middle ears of chinchillas were infected with either a strain of
      GAS capable of forming biofilms in vitro (MGAS5005) or a strain deficient in
      biofilm formation due to the lack of the transcriptional regulator Srv (MGAS5005
      Deltasrv). Infection resulted in the formation of large, macroscopic structures
      within the middle ears of MGAS5005- and MGAS5005 Deltasrv-infected animals. Plate
      counts, scanning electron microscopy, LIVE/DEAD staining, and Gram staining
      revealed a difference in the distributions of MGAS5005 versus MGAS5005 Deltasrv
      in the infected samples. High numbers of CFU of MGAS5005 Deltasrv were isolated
      from the middle ear effusion, and MGAS5005 Deltasrv was found randomly
      distributed throughout the excised macroscopic structure. In contrast, MGAS5005
      was found in densely packed microcolonies indicative of biofilms within the
      excised material from the middle ear. CFU levels of MGAS5005 from the effusion
      were significantly lower than that of MGAS5005 Deltasrv early during the course
      of infection. Allelic replacement of the chromosomally encoded streptococcal
      cysteine protease (speB) in the MGAS5005 Deltasrv background restored biofilm
      formation in vivo. Interestingly, our results suggest that GAS naturally forms a
      biofilm during otitis media but that biofilm formation is not required to
      establish infection following transbullar inoculation of chinchillas.

PMID- 20805337
TI  - Transcriptional response of Leptospira interrogans to iron limitation and
      characterization of a PerR homolog.
AB  - Leptospirosis is a globally significant zoonosis caused by Leptospira spp. Iron
      is essential for growth of most bacterial species. Since iron availability is low
      in the host, pathogens have evolved complex iron acquisition mechanisms to
      survive and establish infection. In many bacteria, expression of iron uptake and
      storage proteins is regulated by Fur. L. interrogans encodes four predicted Fur
      homologs; we have constructed a mutation in one of these, la1857. We conducted
      microarray analysis to identify iron-responsive genes and to study the effects of
      la1857 mutation on gene expression. Under iron-limiting conditions, 43 genes were
      upregulated and 49 genes were downregulated in the wild type. Genes encoding
      proteins with predicted involvement in inorganic ion transport and metabolism
      (including TonB-dependent proteins and outer membrane transport proteins) were
      overrepresented in the upregulated list, while 54% of differentially expressed
      genes had no known function. There were 16 upregulated genes of unknown function
      which are absent from the saprophyte L. biflexa and which therefore may encode
      virulence-associated factors. Expression of iron-responsive genes was not
      significantly affected by mutagenesis of la1857, indicating that LA1857 is not a
      global regulator of iron homeostasis. Upregulation of heme biosynthetic genes and
      a putative catalase in the mutant suggested that LA1857 is more similar to PerR,
      a regulator of the oxidative stress response. Indeed, the la1857 mutant was more
      resistant to peroxide stress than the wild type. Our results provide insights
      into the role of iron in leptospiral metabolism and regulation of the oxidative
      stress response, including genes likely to be important for virulence.

PMID- 20805340
TI  - Combating meaninglessness: on the automatic defense of meaning.
AB  - Research has found that a substantial portion of human cognition occurs beyond
      conscious awareness to satisfy the superordinate goal of maintaining meaning.
      Three experiments used a newly developed method to examine the features of
      meaning and how individuals automatically defend against threats to meaning. In
      Experiment 1, individuals who subliminally processed meaninglessness-related
      words, relative to those in a control group, reported being more religious and
      having more meaningful lives. Experiment 2 extended these results, as individuals
      whose meaning was threatened bolstered alternative domains of meaning (termed
      fluid compensation) by reporting higher self-esteem, need for closure, symbolic
      immortality, and a reduced need to belong. Experiment 3 ruled out an alternative
      explanation and clarified the effects of threatened meaning on one's need to
      belong. These findings elucidate the processes of meaning maintenance in
      sustaining psychological equanimity. Implications for the automatic defense of
      meaning are discussed.

PMID- 20805339
TI  - Peptidoglycan deacetylation in Helicobacter pylori contributes to bacterial
      survival by mitigating host immune responses.
AB  - An oxidative stress-induced enzyme, peptidoglycan deacetylase (PgdA), in the
      human gastric pathogen Helicobacter pylori was previously identified and
      characterized. In this study, we constructed H. pylori pgdA mutants in two mouse
      adapted strains, X47 and B128, to investigate the role of PgdA in vivo (to
      determine the mutants' abilities to colonize mice and to induce an immune
      response). H. pylori pgdA mutant cells showed increased sensitivity to lysozyme
      compared to the sensitivities of the parent strains. We demonstrated that the
      expression of PgdA was significantly induced (3.5-fold) when H. pylori cells were
      in contact with macrophages, similar to the effect observed with oxidative stress
      as the environmental inducer. Using a mouse infection model, we first examined
      the mouse colonization ability of an H. pylori pgdA mutant in X47, a strain
      deficient in the major pathway (cag pathogenicity island [PAI] encoded) for
      delivery of peptidoglycan into host cells. No animal colonization difference
      between the wild type and the mutant was observed 3 weeks after inoculation.
      However, the pgdA mutant showed a significantly attenuated ability to colonize
      mouse stomachs (9-fold-lower bacterial load) at 9 weeks postinoculation. With the
      cag PAI-positive strain B128, a significant colonization difference between the
      wild type and the pgdA mutant was observed at 3 weeks postinoculation (1.32 *
      10(4) versus 1.85 * 10(3) CFU/gram of stomach). To monitor the immune responses
      elicited by H. pylori in the mouse infection model, we determined the
      concentrations of cytokines present in mouse sera. In the mice infected with the
      pgdA mutant strain, we observed a highly significant increase in the level of MIP
      2. In addition, significant increases in interleukin-10 and tumor necrosis factor
      alpha in the pgdA mutant-infected mice compared to the levels in the wild-type H.
      pylori-infected mice were also observed. These results indicated that H. pylori
      peptidoglycan deacetylation is an important mechanism for mitigating host immune
      detection; this likely contributes to pathogen persistence.

PMID- 20805341
TI  - Orthodontic postgraduate education, continuing education and industry marketing.

PMID- 20805344
TI  - Is early Class III protraction facemask treatment effective? A multicentre,
      randomized, controlled trial: 15-month follow-up.
AB  - OBJECTIVE: To investigate the effectiveness of early class III protraction
      facemask treatment in children under 10 years of age. DESIGN: Multicentre,
      randomized controlled trial. SETTING: Eight UK hospital orthodontic units.
      SUBJECTS AND METHODS: Seventy-three patients were randomly allocated, stratified
      for gender, into an early class III protraction facemask group (PFG) (n = 35) and
      a control/no treatment group (CG) (n = 38). OUTCOMES: Dentofacial changes from
      lateral cephalograms and occlusal changes using the peer assessment rating (PAR).
      Self-esteem was assessed using the Piers-Harris children's self-concept scale,
      and the psychosocial impact of malocclusion with an oral aesthetic subjective
      impact scores (OASIS) questionnaire. Temporomandibular joint (TMJ) signs and
      symptoms were also recorded. The time points for data collection were at
      registration (DC1) and 15 months later (DC2). RESULTS: The following mean
      skeletal and occlusal changes occurred from the class III starting point: SNA,
      PFG moved forwards 1.4 degrees (CG forward 0.3 degrees; P = 0.018); SNB, PFG
      moved backwards -0.7 degrees (CG forward 0.8 degrees; P<0.001); ANB, PFG class
      III base improved +2.1 degrees (CG worsened by -0.5 degrees; P<0.001). This
      contributed to an overall difference in ANB between PFG and CG of 2.6 degrees in
      favour of early protraction facemask treatment. The overjet improved +4.4 mm in
      the PFG and marginally changed +0.3 mm in the CG (P<0.001). A 32.2% improvement
      in PAR was shown in the PFG and the CG worsened by 8.6%. There was no increased
      self-esteem (Piers-Harris score) for treated children compared with controls (P =
      0.22). However, there was a reduced impact of malocclusion (OASIS score) for the
      PFG compared with the CG (P = 0.003), suggesting treatment resulted in slightly
      less concern about the tooth appearance. TMJ signs and symptoms were very low at
      DC1 and DC2 and none were reported during active facemask treatment. CONCLUSIONS:
      Early class III orthopaedic treatment, with protraction facemask, in patients
      under 10 years of age, is skeletally and dentally effective in the short term and
      does not result in TMJ dysfunction. Seventy per cent of patients had successful
      treatment, defined as achieving a positive overjet. However, early treatment does
      not seem to confer a clinically significant psychosocial benefit.

PMID- 20805345
TI  - The effect of different surface preparation techniques on the survival
      probabilities of orthodontic brackets bonded to nanofill composite resin.
AB  - OBJECTIVE: To analyze the survival probabilities of different surface preparation
      techniques for bonding brackets to nanofill composite resin. DESIGN: In vitro,
      laboratory study. SETTING: Mahidol University, Bangkok, Thailand. MATERIALS AND
      METHODS: Thirty-five nanofill composite resin specimens/group were subjected to
      four surface preparation techniques as follows: (1) sandblast using aluminium
      oxide powder of 90 microm; (2) abrasion using diamond bur; (3) hydrofluoric acid
      etching for 2 min; and (4) 37% orthophosphoric acid etching for 30 s. Plastic
      conditioner was applied then brackets were bonded. Shear bond strength tests were
      carried out on a universal testing machine. MAIN OUTCOME MEASURES: Shear bond
      strength (MPa) and debonding force (N) were analyzed using Weibull analysis.
      RESULTS: The maximum stress and debonding force levels with a 95% probability of
      survival ranking from highest to lowest were: (1) sandblast group (4.2 MPa, 45.5
      N); (2) diamond bur group (2.2 MPa, 25.3 N); (3) orthophosphoric group (1.9 MPa,
      19.8 N); and (4) hydrofluoric group (0.8 MPa, 10.9 N). There was a significant
      difference in the adhesive remnant index scores between the surface preparation
      techniques (chi squared P<0.001). CONCLUSION: Bonding orthodontic brackets to
      nanofill composite resin materials may result in lower bond strengths and special
      surface preparation techniques might be required to avoid increased numbers of
      bond failures. Surface treatment with sandblasting followed by plastic
      conditioner could increase the survival probability. The use of a diamond bur,
      orthophosphoric etching or hydrofluoric etching cannot be recommended.

PMID- 20805346
TI  - Decontamination procedures for tungsten carbide debonding burs: a cross-sectional
      survey of hospital-based orthodontic departments.
AB  - OBJECTIVE: To determine the current pattern of use and handling of tungsten
      carbide debonding burs (TCDBs) within UK hospital-based orthodontic departments.
      DESIGN: Cross-sectional survey. SUBJECTS AND METHODS: Questionnaires were sent to
      217 departments within the UK and an overall response rate of 93% was achieved.
      RESULTS: Most hospital departments (68%) currently use TCDBs designed for a slow
      handpiece. Just over half (55%) discard their TCDBs after single-use, but only
      24% adequately decontaminate new burs prior to initial use. Almost all those that
      reuse TCDBs decontaminate them in a sterilizer and carry out combinatorial
      presterilization cleaning. The most common methods are manual cleaning followed
      by an ultrasonic bath (26%) or washer-disinfector (15%); or alternatively,
      soaking of burs followed by manual cleaning (13%). For those departments that use
      only a single method, manual cleaning (29%) or a washer-disinfector (10%) are
      most common. In terms of sterilizing TCDBs, 58% used a vacuum phase autoclave and
      13% a downward displacement. CONCLUSIONS: There is wide variation in the handling
      of TCDBs in UK hospital-based orthodontic departments. Decontamination of new
      TCDBs prior to initial use is carried out by less than a third of departments.
      Despite their classification as reusable devices, just over half discard TCDBs
      after single use. However, among those that do reuse TCDBs, almost all
      decontaminate them correctly.

PMID- 20805347
TI  - Decontamination of viable Streptococcus mutans from orthodontic tungsten carbide
      debonding burs. An in vitro microbiological study.
AB  - OBJECTIVES: To investigate the effectiveness of currently recommended
      decontamination procedures on tungsten carbide debonding burs (TCDBs). DESIGN: In
      vitro microbiological study. SETTING: St George's Hospital NHS Trust, UK.
      MATERIALS AND METHODS: A total of 240 extracted tooth surfaces were bonded with
      orthodontic brackets, debonded to leave residual composite and artificially
      contaminated with Streptococcus mutans. INTERVENTION: Sterilized TCDBs in a slow
      handpiece were used to remove this composite before random allocation into one of
      six different decontamination groups of 40 burs each. These included a control
      group that was not decontaminated and a further five that underwent different
      methods of presterilization cleaning within the decontamination process (none,
      manual, ultrasonic, washer disinfector and enzyme soak) followed by sterilization
      in a vacuum phase autoclave at 134 degrees C for 3 min. MAIN OUTCOME MEASURES:
      The burs were placed in brain heart infusion (BHI) broths, incubated for 48 h.
      Following this the broths were inspected for turbidity and microbiological
      analysis was carried out to detect viable bacterial growth. Data were analysed
      using the Kruskal-Wallis test for single ordered data. RESULTS: S. mutans was
      recovered from 39 out of 40 burs in the control group and no burs from the
      decontamination groups, which was statistically significant (P = 0.001). No
      differences were found between decontamination groups (P = 0.271). However, skin
      flora contamination was noted in 17 broths. CONCLUSIONS: The five methods of
      decontaminating TCDBs investigated in this study were effective in removing
      viable S. mutans. Other investigations are required to determine if TCDBs can be
      successfully cleaned of blood and protein residue prior reuse.

PMID- 20805348
TI  - BOS MOrth cases prize 2008.
AB  - This paper describes the clinical orthodontic treatment of two cases that were
      successfully entered for the 2008 intercollegiate MOrth cases prize. The first
      case describes the management of a 12-year-old female with an increased overjet
      treated using a Dynamax functional appliance followed by fixed appliances. The
      second case involves the management of a class II division I malocclusion
      complicated by an unerupted maxillary central incisor and a mandibular first
      molar of poor prognosis.

PMID- 20805349
TI  - A clinical strategy for maxillary molar intrusion using orthodontic mini-implants
      and a customized palatal arch.
AB  - Orthodontic mini-implants are a valuable adjunct in orthodontics and potentially
      expand the orthodontic treatment envelope. In particular, their use may
      revolutionize the treatment of anterior openbites through the application of
      direct molar intrusion. Clinical protocols for mini-implant usage are just
      beginning to evolve and this paper describes the basis for a new clinical
      approach and future research, for the orthodontic treatment of anterior
      openbites.

PMID- 20805350
TI  - Design and management of Twin Blocks: reflections after 30 years of clinical use.
AB  - The objective of this article is to correct some misconceptions that have arisen
      since the introduction of Twin Blocks, to identify factors leading to reduced
      efficiency and increased failure rate, and to improve the clinical application of
      Twin Block technique.

PMID- 20805351
TI  - Developments in making patients' orthodontic choices better.
AB  - CONTEXT: Orthodontics is an unusual speciality as out-patient treatment requires
      patients to attend services regularly for two to three years. Contact with
      services is even longer for some patients referred as children, with their parent
      or carer, and ultimately finishing treatment as autonomous adults. Treatment
      success is highly dependent on patient co-operation. It is vital for patients to
      have as good an understanding as possible of what treatment entails, and whether
      or not it aligns with their expectations, before and during treatment. METHOD:
      This article reviews evidence of the effectiveness of orthodontic information to
      enable patient involvement in treatment regimens. It critiques the current
      provision of information with reference to research from the decision and
      behaviour sciences about how people make sense of information when making
      treatment decisions. FINDINGS: Orthodontists provide a lot of verbal and written
      information about the 'facts' of treatment. This type of information is unlikely
      to facilitate patients' decisions about, or adherence with, treatments. There is
      a paucity of evidence describing how: (1) patients make sense of orthodontic
      problems and treatments, (2) parents manage decision making about their child's
      treatment, and (3) variation in information needs across the lifespan and
      treatment experience. PRACTICE IMPLICATIONS: We identified a set of questions to
      help service providers think critically about the effectiveness of their
      information provision. Further empirical research is needed to provide evidence
      to ensure the information included within orthodontic leaflets is relevant to
      patients and can be assimilated into their existing representations of the
      problem and treatment.

PMID- 20805353
TI  - Eruption of an ectopic horizontal maxillary canine.

PMID- 20805354
TI  - The beta/Gcd7 subunit of eukaryotic translation initiation factor 2B (eIF2B), a
      guanine nucleotide exchange factor, is crucial for binding eIF2 in vivo.
AB  - Eukaryotic translation initiation factor 2B (eIF2B) is the guanine nucleotide
      exchange factor (GEF) for eukaryotic translation initiation factor 2, which
      stimulates formation of the eIF2-GTP-Met-tRNA(i)(Met) ternary complex (TC) in a
      manner inhibited by phosphorylated eIF2 [eIF2(alphaP)]. While eIF2B contains five
      subunits, the epsilon/Gcd6 subunit is sufficient for GEF activity in vitro. The
      delta/Gcd2 and beta/Gcd7 subunits function with alpha/Gcn3 in the eIF2B
      regulatory subcomplex that mediates tight, inhibitory binding of eIF2(alphaP)
      GDP, but the essential functions of delta/Gcd2 and beta/Gcd7 are not well
      understood. We show that the depletion of wild-type beta/Gcd7, three lethal
      beta/Gcd7 amino acid substitutions, and a synthetically lethal combination of
      substitutions in beta/Gcd7 and eIF2alpha all impair eIF2 binding to eIF2B without
      reducing epsilon/Gcd6 abundance in the native eIF2B-eIF2 holocomplex.
      Additionally, beta/Gcd7 mutations that impair eIF2B function display extensive
      allele-specific interactions with mutations in the S1 domain of eIF2alpha
      (harboring the phosphorylation site), which binds to eIF2B directly. Consistent
      with this, beta/Gcd7 can overcome the toxicity of eIF2(alphaP) and rescue native
      eIF2B function when overexpressed with delta/Gcd2 or gamma/Gcd1. In aggregate,
      these findings provide compelling evidence that beta/Gcd7 is crucial for binding
      of substrate by eIF2B in vivo, beyond its dispensable regulatory role in the
      inhibition of eIF2B by eIF (alphaP).

PMID- 20805355
TI  - Inhibition of human peptide deformylase disrupts mitochondrial function.
AB  - Deformylases are metalloproteases in bacteria, plants, and humans that remove the
      N-formyl-methionine off peptides in vitro. The human homolog of peptide
      deformylase (HsPDF) resides in the mitochondria, along with its putative
      formylated substrates; however, the cellular function of HsPDF remains elusive.
      Here we report on the function of HsPDF in mitochondrial translation and
      oxidative phosphorylation complex biogenesis. Functional HsPDF appears to be
      necessary for the accumulation of mitochondrial DNA-encoded proteins and assembly
      of new respiratory complexes containing these proteins. Consequently, inhibition
      of HsPDF reduces respiratory function and cellular ATP levels, causing dependence
      on aerobic glycolysis for cell survival. A series of structurally different HsPDF
      inhibitors and control peptidase inhibitors confirmed that inhibition of HsPDF
      decreases mtDNA-encoded protein accumulation. Therefore, HsPDF appears to have a
      role in maintenance of mitochondrial respiratory function, and this function is
      analogous to that of chloroplast PDF.

PMID- 20805356
TI  - Chromatin remodeling around nucleosome-free regions leads to repression of
      noncoding RNA transcription.
AB  - Nucleosome-free regions (NFRs) at the 5' and 3' ends of genes are general sites
      of transcription initiation for mRNA and noncoding RNA (ncRNA). The presence of
      NFRs within transcriptional regulatory regions and the conserved location of
      transcription start sites at NFRs strongly suggest that the regulation of NFRs
      profoundly affects transcription initiation. To date, multiple factors are known
      to facilitate transcription initiation by positively regulating the formation
      and/or size of NFRs in vivo. However, mechanisms to repress transcription by
      negatively regulating the size of NFRs have not been identified. We identified
      four distinct classes of NFRs located at the 5' and 3' ends of genes, within open
      reading frames (ORFs), and far from ORFs. The ATP-dependent chromatin-remodeling
      enzyme Isw2 was found enriched at all classes of NFRs. Analysis of RNA levels
      also demonstrated Isw2 is required to repress ncRNA transcription from many of
      these NFRs. Thus, by the systematic annotation of NFRs across the yeast genome
      and analysis of ncRNA transcription, we established, for the first time, a
      mechanism by which NFR size is negatively regulated to repress ncRNA
      transcription from NFRs. Finally, we provide evidence suggesting that one
      biological consequence of repression of ncRNA, by Isw2 or by the exosome, is
      prevention of transcriptional interference of mRNA.

PMID- 20805357
TI  - The ubiquitin carboxyl hydrolase BAP1 forms a ternary complex with YY1 and HCF-1
      and is a critical regulator of gene expression.
AB  - The candidate tumor suppressor BAP1 is a deubiquitinating enzyme (DUB) involved
      in the regulation of cell proliferation, although the molecular mechanisms
      governing its function remain poorly defined. BAP1 was recently shown to interact
      with and deubiquitinate the transcriptional regulator host cell factor 1 (HCF-1).
      Here we show that BAP1 assembles multiprotein complexes containing numerous
      transcription factors and cofactors, including HCF-1 and the transcription factor
      Yin Yang 1 (YY1). Through its coiled-coil motif, BAP1 directly interacts with the
      zinc fingers of YY1. Moreover, HCF-1 interacts with the middle region of YY1
      encompassing the glycine-lysine-rich domain and is essential for the formation of
      a ternary complex with YY1 and BAP1 in vivo. BAP1 activates transcription in an
      enzymatic-activity-dependent manner and regulates the expression of a variety of
      genes involved in numerous cellular processes. We further show that BAP1 and HCF
      1 are recruited by YY1 to the promoter of the cox7c gene, which encodes a
      mitochondrial protein used here as a model of BAP1-activated gene expression. Our
      findings (i) establish a direct link between BAP1 and the transcriptional control
      of genes regulating cell growth and proliferation and (ii) shed light on a novel
      mechanism of transcription regulation involving ubiquitin signaling.

PMID- 20805358
TI  - Regulation of memory CD8 T-cell differentiation by cyclin-dependent kinase
      inhibitor p27Kip1.
AB  - Induction of potent T-cell memory is the goal of vaccinations, but the molecular
      mechanisms that regulate the formation of memory CD8 T cells are not well
      understood. Despite the recognition that controls of cellular proliferation and
      apoptosis govern the number of memory T cells, the cell cycle regulatory
      mechanisms that control these key cellular processes in CD8 T cells during an
      immune response are poorly defined. Here, we have identified the cyclin-dependent
      kinase inhibitor p27(Kip1) as a critical regulator of the CD8 T-cell homeostasis
      at all phases of the T-cell response to an acute viral infection in mice. By
      acting as a timer for cell cycle exit, p27(Kip1) curtailed the programmed
      expansion of interleukin-2-producing memory precursors and markedly limited the
      magnitude and quality of CD8 T-cell memory. In the absence of p27(Kip1), CD8 T
      cells showed superior recall responses shortly after vaccination with recombinant
      Listeria monocytogenes. Additionally, we show that p27(Kip1) constrains
      proliferative renewal of memory CD8 T cells, especially of the effector memory
      subset. These findings provide critical insights into the cell cycle regulation
      of CD8 T-cell homeostasis and suggest that modulation of p27(Kip1) could bolster
      vaccine-induced T-cell memory and protective immunity.

PMID- 20805359
TI  - Cortactin modulates RhoA activation and expression of Cip/Kip cyclin-dependent
      kinase inhibitors to promote cell cycle progression in 11q13-amplified head and
      neck squamous cell carcinoma cells.
AB  - The cortactin oncoprotein is frequently overexpressed in head and neck squamous
      cell carcinoma (HNSCC), often due to amplification of the encoding gene (CTTN).
      While cortactin overexpression enhances invasive potential, recent research
      indicates that it also promotes cell proliferation, but how cortactin regulates
      the cell cycle machinery is unclear. In this article we report that stable short
      hairpin RNA-mediated cortactin knockdown in the 11q13-amplified cell line FaDu
      led to increased expression of the Cip/Kip cyclin-dependent kinase inhibitors
      (CDKIs) p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) and inhibition of S-phase entry.
      These effects were associated with increased binding of p21(WAF1/Cip1) and
      p27(Kip1) to cyclin D1- and E1-containing complexes and decreased retinoblastoma
      protein phosphorylation. Cortactin regulated expression of p21(WAF1/Cip1) and
      p27(Kip1) at the transcriptional and posttranscriptional levels, respectively.
      The direct roles of p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) downstream of
      cortactin were confirmed by the transient knockdown of each CDKI by specific
      small interfering RNAs, which led to partial rescue of cell cycle progression.
      Interestingly, FaDu cells with reduced cortactin levels also exhibited a
      significant diminution in RhoA expression and activity, together with decreased
      expression of Skp2, a critical component of the SCF ubiquitin ligase that targets
      p27(Kip1) and p57(Kip2) for degradation. Transient knockdown of RhoA in FaDu
      cells decreased expression of Skp2, enhanced the level of Cip/Kip CDKIs, and
      attenuated S-phase entry. These findings identify a novel mechanism for
      regulation of proliferation in 11q13-amplified HNSCC cells, in which
      overexpressed cortactin acts via RhoA to decrease expression of Cip/Kip CDKIs,
      and highlight Skp2 as a downstream effector for RhoA in this process.

PMID- 20805361
TI  - Cytokine-induced immune complex binding to the high-affinity IgG receptor,
      FcgammaRI, in the presence of monomeric IgG.
AB  - FcgammaRI is the sole high-affinity immunoglobulin G (IgG) receptor on
      leukocytes. Its role in immunity and the clearance of opsonized particles has
      been challenged, as the receptor function may well be hindered by serum IgG.
      Here, we document immune complex binding by FcgammaRI to be readily enhanced by
      cytokine stimulation, whereas binding of monomeric IgG only modestly increased.
      Enhanced immune complex binding was independent of FcgammaRI surface expression
      levels. FcgammaRI, saturated with prebound IgG, was found capable of effective
      immune complex binding upon cytokine stimulation. Cytokine-enhanced binding was
      observed across a variety of immune complexes, including huIgG3- or mIgG2a
      opsonized red blood cells, rituximab- or ofatumumab-opsonized B-cell lymphoma,
      and cetuximab-opsonized glioblastoma cells. This study contributes to our
      understanding of how FcgammaRI can participate in the clearance of opsonized
      particles despite saturation by monomeric IgG.

PMID- 20805360
TI  - Polyamines regulate the stability of JunD mRNA by modulating the competitive
      binding of its 3' untranslated region to HuR and AUF1.
AB  - Polyamines critically regulate all mammalian cell growth and proliferation by
      mechanisms such as the repression of growth-inhibitory proteins, including JunD.
      Decreasing the levels of cellular polyamines stabilizes JunD mRNA without
      affecting its transcription, but the exact mechanism whereby polyamines regulate
      JunD mRNA degradation has not been elucidated. RNA-binding proteins HuR and AUF1
      associate with labile mRNAs bearing AU-rich elements located in the 3'
      untranslated regions (3'-UTRs) and modulate their stability. Here, we show that
      JunD mRNA is a target of HuR and AUF1 and that polyamines modulate JunD mRNA
      degradation by altering the competitive binding of HuR and AUF1 to the JunD 3'
      UTR. The depletion of cellular polyamines enhanced HuR binding to JunD mRNA and
      decreased the levels of JunD transcript associated with AUF1, thus stabilizing
      JunD mRNA. The silencing of HuR increased AUF1 binding to the JunD mRNA,
      decreased the abundance of HuR-JunD mRNA complexes, rendered the JunD mRNA
      unstable, and prevented increases in JunD mRNA and protein in polyamine-deficient
      cells. Conversely, increasing the cellular polyamines repressed JunD mRNA
      interaction with HuR and enhanced its association with AUF1, resulting in an
      inhibition of JunD expression. These results indicate that polyamines modulate
      the stability of JunD mRNA in intestinal epithelial cells through HuR and AUF1
      and provide new insight into the molecular functions of cellular polyamines.

PMID- 20805362
TI  - Transformation by Tribbles homolog 2 (Trib2) requires both the Trib2 kinase
      domain and COP1 binding.
AB  - Tribbles homolog 2 (Trib2) is a pseudokinase that induces acute myelogenous
      leukemia (AML) in mice and is highly expressed in a subset of human AML. Trib2
      has 3 distinct regions, a proline-rich N-terminus, a serine/threonine kinase
      homology domain, and a C-terminal constitutive photomorphogenesis 1 (COP1)
      binding domain. We performed a structure-function analysis of Trib2 using in
      vitro and in vivo assays. The N-terminus was not required for Trib2-induced AML.
      Deletion or mutation of the COP1-binding site abrogated the ability of Trib2 to
      degrade CCAAT/enhancer-binding protein-alpha (C/EBP-alpha), block granulocytic
      differentiation, and to induce AML in vivo. Furthermore, COP1 knockdown inhibited
      the ability of Trib2 to degrade C/EBP-alpha, showing that it is important for
      mediating Trib2 activity. We also show that the Trib2 kinase domain is essential
      for its function. Trib2 contains variant catalytic loop sequences, compared with
      conventional kinases, that we show are necessary for Trib2 activity. The kinase
      domain mutants bind, but cannot efficiently degrade, C/EBP-alpha. Together, our
      data demonstrate that Trib2 can bind both COP1 and C/EBP-alpha, leading to
      degradation of C/EBP-alpha. Identification of the functional regions of Trib2
      that are essential to its oncogenic role provides the basis for developing
      inhibitors that will block Trib functions in cancer.

PMID- 20805363
TI  - How I treat elderly patients with diffuse large B-cell lymphoma.
AB  - Enormous progress has been made in the treatment of diffuse large B-cell lymphoma
      (DLBCL), mostly due to the anti-CD20 antibody rituximab. More than 50% of elderly
      DLBCL patients can be expected to be cured by modern immunochemotherapy. The
      standard chemotherapy partner of rituximab is the CHOP (cyclophosphamide,
      doxorubicin, vincristine, and prednisone) regimen. Elderly patients need
      particular attention and thorough evaluation if they are suited for the standard
      treatment or if they are candidates for palliative treatment. Rigorous supportive
      care including anti-infectious prophylaxis and growth factor support are
      mandatory. Whether there is still a role of additive radiotherapy in the R-CHOP
      era is under debate. While further intensification of chemotherapy might hardly
      be feasible in elderly patients, dose and schedule of rituximab appear to be
      optimizable. Patients failing after R-CHOP are a particular challenge as are
      frail patients who are not fit enough for R-CHOP. Further progress can be
      expected from novel antibodies and small molecules that interfere with signal
      transduction pathways essential for the survival of the lymphoma cell. To achieve
      this goal, prospective trials with large numbers of patients are necessary for
      which the continuous commitment of patients and physicians is indispensable.

PMID- 20805364
TI  - Functional roles of aspartate residues of the proton-coupled folate transporter
      (PCFT-SLC46A1); a D156Y mutation causing hereditary folate malabsorption.
AB  - The proton-coupled folate transporter (PCFT; SLC46A1) mediates folate transport
      into enterocytes in the proximal small intestine; pcft loss-of-function mutations
      are the basis for hereditary folate malabsorption. The current study explored the
      roles of Asp residues in PCFT function. A novel, homozygous, loss-of-function
      mutation, D156Y, was identified in a child of Pakistani origin with hereditary
      folate malabsorption. Of the 6 other conserved Asp residues, only one, D109, is
      shown to be required for function. D156Y, along with a variety of other
      substitutions at this site (Trp, Phe, Val, Asn, or Lys), lacked function due to
      instability of the PCFT protein. Substantial function was preserved with Glu,
      Gly, and, to a lesser extent, with Ser, Thr, and Ala substitutions. This
      correlated with PCFT bio-tinylated at the cell surface. In contrast, all D109
      mutants, including D109E, lacked function irrespective of pH (4.5, 5.5, and 7.4)
      or substrate concentration (0.5-100 MUM), despite surface expression comparable
      to wild-type PCFT. Hence, D156 plays a critical role in PCFT protein stability,
      and D109, located in the first intracellular loop between the second and third
      transmembrane domains, is absolutely required for PCFT function.

PMID- 20805365
TI  - IDH1 mutations are detected in 6.6% of 1414 AML patients and are associated with
      intermediate risk karyotype and unfavorable prognosis in adults younger than 60
      years and unmutated NPM1 status.
AB  - Mutations in the IDH1 gene at position R132 coding for the enzyme cytosolic
      isocitrate dehydrogenase are known in glioma and have recently been detected also
      in acute myeloid leukemia (AML). These mutations result in an accumulation of
      alpha-ketoglutarate to R (2)-2-hydroxyglutarate (2HG). To further clarify the
      role of this mutation in AML, we have analyzed IDH1R132 in 1414 AML patients. We
      detected IDH1R132 mutations in 93 of 1414 patients (6.6%) with a clear prevalence
      in intermediate risk karyotype group (10.4%, P < .001). Although IDH1R132
      mutations can incidentally occur together with all other molecular markers, there
      were strong associations with NPM1 mutations (14.2% vs 5.4% in NPM1wt, P < .001)
      and MLL-PTD (18.2% vs 7.0% in MLLwt, P = .020). IDH1-mutated cases more often had
      AML without maturation/French-American-British M1 (P < .001), an immature
      immunophenotype, and female sex (8.7% vs 4.7% in male, P = .003) compared with
      IDH1wt cases. Prognosis was adversely affected by IDH1 mutations with trend for
      shorter overall survival (P = .110), a shorter event-free survival (P < .003) and
      a higher cumulative risk for relapse (P = .001). IDH1 mutations were of
      independent prognostic relevance for event-free survival (P = .039) especially in
      the age group < 60 years (P = .028). In conclusion, these data show that IDH1R132
      may significantly add information regarding characterization and prognostication
      in AML.

PMID- 20805367
TI  - BBS10 mutations are common in 'Meckel'-type cystic kidneys.
AB  - BACKGROUND: Bardet-Biedl syndrome (BBS) is a genetically heterogeneous,
      multisystemic disorder characterised by progressive retinal dystrophy, obesity,
      hypogenitalism, learning difficulties, renal abnormalities and postaxial
      polydactyly, with only the last two antenatally observable. BBS is inherited as
      an autosomal recessive disorder, and 14 genes have been identified to date (BBS1
      BBS14). In addition, a complex digenic inheritance has been established in some
      families. Mutations of the BBS10 gene on chromosome 12q21.2 account for 20% of
      BBS cases. METHODS: Given the fact that mutations in BBS genes have already been
      found in Meckel-like fetuses, and in light of the major contribution of BBS10 to
      BBS, the BBS10 gene was sequenced in 20 fetal cases and a child diagnosed
      antenatally presenting with characteristic renal anomalies and polydactyly, but
      without biliary dysgenesis. RESULTS: Recessive mutations were identified at the
      BBS10 locus in five cases: four fetuses and a child. Interestingly, one of them
      had situs ambiguus, a rare feature in BBS. In the child, BBS gene screening
      identified a heterozygous BBS6 nonsense mutation in addition to the homozygous
      BBS10 mutation, in accordance with the suggested multigenic inheritance of the
      disease. CONCLUSIONS: These results confirm that BBS is underdiagnosed
      antenatally and should systematically be suspected in fetuses with severe cystic
      kidneys leading to oligoamnios and fetal or perinatal death. Moreover, this study
      confirms the high frequency of BBS10 mutations, particularly of the
      p.Cys91LeufsX5 allele, including severe lethal cases.

PMID- 20805366
TI  - A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo
      cytotoxicity in multiple myeloma.
AB  - Bortezomib therapy has proven successful for the treatment of relapsed,
      relapsed/refractory, and newly diagnosed multiple myeloma (MM). At present,
      bortezomib is available as an intravenous injection, and its prolonged treatment
      is associated with toxicity and development of drug resistance. Here we show that
      the novel proteasome inhibitor ONX 0912, a tripeptide epoxyketone, inhibits
      growth and induces apoptosis in MM cells resistant to conventional and bortezomib
      therapies. The anti-MM activity of ONX-0912 is associated with activation of
      caspase-8, caspase-9, caspase-3, and poly(ADP) ribose polymerase, as well as
      inhibition of migration of MM cells and angiogenesis. ONX 0912, like bortezomib,
      predominantly inhibits chymotrypsin-like activity of the proteasome and is
      distinct from bortezomib in its chemical structure. Importantly, ONX 0912 is
      orally bioactive. In animal tumor model studies, ONX 0912 significantly reduced
      tumor progression and prolonged survival. Immununostaining of MM tumors from ONX
      0912-treated mice showed growth inhibition, apoptosis, and a decrease in
      associated angiogenesis. Finally, ONX 0912 enhances anti-MM activity of
      bortezomib, lenalidomide dexamethasone, or pan-histone deacetylase inhibitor.
      Taken together, our study provides the rationale for clinical protocols
      evaluating ONX 0912, either alone or in combination, to improve patient outcome
      in MM.

PMID- 20805368
TI  - Mosaicism for oncogenic G12D KRAS mutation associated with epidermal nevus,
      polycystic kidneys and rhabdomyosarcoma.
AB  - BACKGROUND: Epidermal nevus (EN) is a congenital disorder characterised by
      hyperpigmented epidermal thickening following a Blaschko's line. It is due to
      somatic mutations in either FGFR3 or PIK3CA in half of the cases, and remains of
      unknown genetic origin in the other half. EN is also seen as part of complex
      developmental disorders or in association with bladder carcinomas, also related
      to FGFR3 and PIK3CA mutations. Mosaic mutations of these genes have been
      occasionally found in syndromic EN. CASE REPORT: The co-occurrence of EN,
      rhabdomyosarcoma, polycystic kidneys and growth retardation in an infant is
      described. RESULTS: An oncogenic G12D KRAS mutation was detected in both the
      epidermal component of the EN and in the rhabdomyosarcoma but not in the dermal
      component of the EN lesion or in unaffected tissues, including normal skin or
      blood. CONCLUSION: This report shows for the first time that a KRAS mutation in
      epiderma causes EN. Observation of the same G12D KRAS mutation in two distinct
      regions of the body strongly suggests a somatic mosaicism. Finally, this report
      highlights the potentially underestimated importance of mosaic oncogene mutations
      in childhood cancers.

PMID- 20805369
TI  - Polymorphisms at 16p13 are associated with systemic lupus erythematosus in the
      Chinese population.
AB  - BACKGROUND: Chromosomal region 16p13 has been reported to harbour variants
      associated with several autoimmune diseases, including type I diabetes,
      rheumatoid arthritis and multiple sclerosis. OBJECTIVE: To test whether variants
      in the 16p13 region are also associated with systemic lupus erythematosus (SLE)
      by performing a candidate locus study in the Chinese Han population. METHODS: Tag
      single nucleotide polymorphisms (SNPs) encompassing 50 kb upstream and downstream
      of the 250 kb linkage disequilibrium block, previously implicated in several
      autoimmune diseases, were analysed in 1047 patients with SLE and 1205 controls.
      The SNP showing the strongest association with SLE was then replicated in an
      independent cohort of 1643 cases and 5930 controls. RESULTS AND CONCLUSIONS: The
      association between SNP rs12599402 and SLE reached the genome-wide significance
      level (p<5 * 10-8). The SNP was likely to tag the same functional variant as
      previously reported in European populations. The results suggested that the
      chromosomal region at 16p13 contains common susceptibility genes for different
      immune-mediated disorders.

PMID- 20805370
TI  - Abnormal respiratory cilia in non-syndromic Leber congenital amaurosis with
      CEP290 mutations.
AB  - BACKGROUND: Leber congenital amaurosis (LCA) is the earliest and most severe
      inherited retinal degeneration. Isolated forms of LCA frequently result from
      mutation of the CEP290 gene which is expressed in various ciliated tissues.
      METHODS: Seven LCA patients with CEP290 mutations were investigated to study
      otorhinolaryngologic phenotype and respiratory cilia. Nasal biopsies and brushing
      were performed to study cilia ultrastructure using transmission electron
      microscopy and ciliary beating using high-speed videomicroscopy, respectively.
      CEP290 expression in normal nasal epithelium was studied using real-time RT-PCR.
      RESULTS: When electron microscopy was feasible (5/7), high levels of respiratory
      cilia defects were detected. The main defects concerned dynein arms, central
      complex and/or peripheral microtubules. All patients had a rarefaction of
      ciliated cells and a variable proportion of short cilia. Frequent but moderate
      and heterogeneous clinical and ciliary beating abnormalities were found. CEP290
      was highly expressed in the neural retina and nasal epithelial cells compared
      with other tissues. DISCUSSION: These data provide the first clear demonstration
      of respiratory cilia ultrastructural defects in LCA patients with CEP290
      mutations. The frequency of these findings in LCA patients along with the high
      expression of CEP290 in nasal epithelium suggest that CEP290 has an important
      role in the proper development of both the respiratory ciliary structures and the
      connecting cilia of photoreceptors. The presence of respiratory symptoms in
      patients could represent additional clinical criteria to direct CEP290 genotyping
      of patients affected with the genetically heterogeneous cone-rod dystrophy
      subtype of LCA.

PMID- 20805371
TI  - Mutations in PCDH21 cause autosomal recessive cone-rod dystrophy.
AB  - BACKGROUND: Cone-rod dystrophy is a retinal dystrophy with early loss of cone
      photoreceptors and a parallel or subsequent loss of rod photoreceptors. It may be
      syndromic, but most forms are non-syndromic with autosomal dominant, autosomal
      recessive or X-linked recessive inheritance. METHODS AND RESULTS: We identified a
      small consanguineous family with six patients with cone-rod dystrophy from the
      Faroe Islands. Homozygosity mapping revealed a single homozygous locus of 4.2 Mb
      on chromosome 10q23.1-q23.2, encompassing 11 genes. All patients were homozygous
      for a 1-bp duplication in PCDH21, c.524dupA, which results in a frameshift and a
      premature stop codon (p.Q175QfsX47). CONCLUSION: To our knowledge, this is the
      first report of mutations in PCDH21 as a cause of human disease. PCDH21 is highly
      expressed in the retinal photoreceptor cells. It encodes protocadherin 21, which
      belongs to the cadherin superfamily of large cell surface proteins characterised
      by a variable number of extracellular cadherin domains. A PCDH21 knockout mouse
      model has previously shown loss of photoreceptor cells and abnormal cone and rod
      function, similar to the findings in the patients.

PMID- 20805372
TI  - A novel HER2-positive breast cancer phenotype arising from germline TP53
      mutations.
AB  - INTRODUCTION: The Li-Fraumeni Syndrome is caused by a germline TP53 mutation and
      is associated with a high risk of breast cancer at young ages. Basal (triple
      negative) breast cancers are now well recognised to be a typical sub-type of
      breast cancer developing in a large proportion of BRCA1 gene carriers. We
      considered whether a similar narrow sub-type of breast cancer was found in TP53
      gene mutation carriers. OBJECTIVE: A hypothesis generating study to investigate
      whether there are specific breast tumour characteristics associated with germline
      TP53 mutations. METHODS: Pathological characteristics in 12 breast cancers
      arising in nine patients carrying pathogenic TP53 mutations were compared to a
      reference panel of 231 young onset breast tumours included in the POSH study.
      RESULTS: Patients carrying a TP53 mutation showed a significantly higher
      likelihood of developing a breast cancer with Human Epidermal growth factor
      Receptor (HER2) amplification (83%) when compared to the cohort of young onset
      breast cancer cases (16%); ER and PR status were equivalent between groups.
      CONCLUSION: These findings suggest that breast cancer developing on a background
      of an inherited TP53 mutation is highly likely to present with amplification of
      HER2.

PMID- 20805373
TI  - The emotional timeline of September 11, 2001.

PMID- 20805375
TI  - Comment on: Robertson (2010) Islet transplantation a decade later and strategies
      for filling a half-full glass. Diabetes;59:1285-1291.

PMID- 20805374
TI  - Anti-mitogenic effects of beta-agonists and PGE2 on airway smooth muscle are PKA
      dependent.
AB  - Inhaled beta-agonists are effective airway smooth muscle (ASM)-relaxing agents
      that help reverse bronchoconstriction in asthma, but their ability to affect the
      aberrant ASM growth that also occurs with asthma is poorly understood. beta
      Agonists exhibit PKA-dependent antimitogenic effects in several cell types.
      However, recent studies suggest that Epac, and not PKA, mediates the
      antimitogenic effect of cAMP in both ASM and fibroblasts. This study aims to
      clarify the role of PKA in mediating the effect of G(s)-coupled receptors on
      human ASM growth. Pretreatment of ASM cultures with beta-agonists albuterol,
      isoproterenol, or salmeterol (100 nM to 10 MUM) caused a significant (~ 25-30%)
      inhibition of EGF-stimulated ASM thymidine incorporation and cell proliferation,
      whereas a much greater inhibition was observed from pretreatment with PGE(2) (75
      80%). However, all agents were ineffective in cells expressing GFP chimeras of
      either PKI (a PKA inhibitor) or a mutant PKA regulatory subunit relative to the
      control cells expressing GFP. The antimitogenic efficacy of PGE(2) in inhibiting
      control cultures was associated with greater ability to stimulate sustained PKA
      activation and greater inhibition of late-phase promitogenic p42/p44 and PI3K
      activities. These findings suggest that therapeutic approaches enabling superior
      PKA activation in ASM will be most efficacious in deterring ASM growth.

PMID- 20805377
TI  - Comment on: Chauhan et al. (2010) Impact of common variants of PPARG, KCNJ11,
      TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 on the risk of type 2 diabetes
      in 5,164 Indians. Diabetes;59:2068-2074.

PMID- 20805379
TI  - Comment on: Yang et al. (2010) Associations of hyperglycemia and insulin usage
      with the risk of cancer in type 2 diabetes: the Hong Kong Diabetes Registry.
      Diabetes;59:1254-1260.

PMID- 20805381
TI  - Comment on: Matsuoka et al. (2010) Regulation of MafA expression in pancreatic
      beta-cells in db/db mice with diabetes. Diabetes;59:1709-1720.

PMID- 20805382
TI  - Antigen-specific immunotherapy for type 1 diabetes: maximizing the potential.

PMID- 20805384
TI  - Pancreatic islet transplants and IDO: when starving the enemy does you good.

PMID- 20805383
TI  - Recent advances and prospects in the differentiation of pancreatic cells from
      human embryonic stem cells.
AB  - Recent studies with human embryonic stem (hES) cells have established new
      protocols for substantial generation of pancreatic progenitors from definitive
      endoderm. These findings add to the efficient derivation of definitive endoderm,
      which is controlled by Wnt and Nodal pathways, and delineate a step forward in
      the quest for alternative beta-cell sources. It also indicates that critical
      refining of the available strategies might help define a universal protocol for
      pancreatic differentiation applicable to several cell lines, therefore offering
      the possibility for transplantation of immune-matched or patient-specific hES
      derived beta-cells. We appraise here the fundamental role that bone morphogenetic
      protein, fibroblast growth factor, and retinoid signaling play during pancreas
      development, and describe a fundamental emergence of their combination in recent
      studies that generated pancreatic cells from hES cells. We finally enumerate some
      prospects that might improve further differentiation of the progenitor cells into
      functional beta-cells needed in diabetes cell therapy.

PMID- 20805385
TI  - Obesity and insulin resistance: an ongoing saga.

PMID- 20805386
TI  - A novel clinically relevant strategy to abrogate autoimmunity and regulate
      alloimmunity in NOD mice.
AB  - OBJECTIVE: To investigate a new clinically relevant immunoregulatory strategy
      based on treatment with murine Thymoglobulin mATG Genzyme and CTLA4-Ig in NOD
      mice to prevent allo- and autoimmune activation using a stringent model of islet
      transplantation and diabetes reversal. RESEARCH DESIGN AND METHODS: Using
      allogeneic islet transplantation models as well as NOD mice with recent onset
      type 1 diabetes, we addressed the therapeutic efficacy and immunomodulatory
      mechanisms associated with a new immunoregulatory protocol based on prolonged low
      dose mATG plus CTLA4-Ig. RESULTS: BALB/c islets transplanted into hyperglycemic
      NOD mice under prolonged mATG+CTLA4-Ig treatment showed a pronounced delay in
      allograft rejection compared with untreated mice (mean survival time: 54 vs. 8
      days, P < 0.0001). Immunologic analysis of mice receiving transplants revealed a
      complete abrogation of autoimmune responses and severe downregulation of
      alloimmunity in response to treatment. The striking effect on autoimmunity was
      confirmed by 100% diabetes reversal in newly hyperglycemic NOD mice and 100%
      indefinite survival of syngeneic islet transplantation (NOD.SCID into NOD mice).
      CONCLUSIONS: The capacity to regulate alloimmunity and to abrogate the autoimmune
      response in NOD mice in different settings confirmed that prolonged mATG+CTLA4-Ig
      treatment is a clinically relevant strategy to translate to humans with type 1
      diabetes.

PMID- 20805387
TI  - Cellularity and adipogenic profile of the abdominal subcutaneous adipose tissue
      from obese adolescents: association with insulin resistance and hepatic
      steatosis.
AB  - OBJECTIVE: We explored whether the distribution of adipose cell size, the
      estimated total number of adipose cells, and the expression of adipogenic genes
      in subcutaneous adipose tissue are linked to the phenotype of high visceral and
      low subcutaneous fat depots in obese adolescents. RESEARCH DESIGN AND METHODS: A
      total of 38 adolescents with similar degrees of obesity agreed to have a
      subcutaneous periumbilical adipose tissue biopsy, in addition to metabolic (oral
      glucose tolerance test and hyperinsulinemic euglycemic clamp) and imaging studies
      (MRI, DEXA, (1)H-NMR). Subcutaneous periumbilical adipose cell-size distribution
      and the estimated total number of subcutaneous adipose cells were obtained from
      tissue biopsy samples fixed in osmium tetroxide and analyzed by Beckman Coulter
      Multisizer. The adipogenic capacity was measured by Affymetrix GeneChip and
      quantitative RT-PCR. RESULTS: Subjects were divided into two groups: high versus
      low ratio of visceral to visceral + subcutaneous fat (VAT/[VAT+SAT]). The cell
      size distribution curves were significantly different between the high and low
      VAT/(VAT+SAT) groups, even after adjusting for age, sex, and ethnicity (MANOVA P
      = 0.035). Surprisingly, the fraction of large adipocytes was significantly lower
      (P < 0.01) in the group with high VAT/(VAT+SAT), along with the estimated total
      number of large adipose cells (P < 0.05), while the mean diameter was increased
      (P < 0.01). From the microarray analyses emerged a lower expression of
      lipogenesis/adipogenesis markers (sterol regulatory element binding protein-1,
      acetyl-CoA carboxylase, fatty acid synthase) in the group with high
      VAT/(VAT+SAT), which was confirmed by RT-PCR. CONCLUSIONS: A reduced lipo
      /adipogenic capacity, fraction, and estimated number of large subcutaneous
      adipocytes may contribute to the abnormal distribution of abdominal fat and
      hepatic steatosis, as well as to insulin resistance in obese adolescents.

PMID- 20805388
TI  - Should moxifloxacin be used for the treatment of extensively drug-resistant
      tuberculosis? An answer from a murine model.
AB  - The prevalence of extensively drug-resistant tuberculosis (XDR-TB), defined as TB
      that is resistant to isoniazid, rifampin, fluoroquinolones, and aminoglycosides,
      is rising worldwide. The extent of Mycobacterium tuberculosis resistance to
      fluoroquinolones depends on the mutation in the DNA gyrase, the only target of
      fluoroquinolones. The MIC of moxifloxacin, the most active fluoroquinolone
      against M. tuberculosis, may be lower than its peak serum level for some
      ofloxacin-resistant strains of Mycobacterium tuberculosis. Therefore, if the MIC
      of moxifloxacin is lower than its peak serum level, it may be effective against
      XDR-TB. Our objective was to determine the efficacy of moxifloxacin in treating
      ofloxacin-resistant TB. We selected isogenic fluoroquinolone-resistant mutants of
      M. tuberculosis H37Rv in vivo. We infected Swiss mice with either wild-type H37Rv
      or one of three mutant strains with different MICs that are commonly seen in
      clinical practice. The MICs of the mutant strains ranged from below to above the
      peak moxifloxacin level seen in humans (3 MUg/ml). Each mouse was treated with
      one of four moxifloxacin doses for 1 month. Moxifloxacin was effective against
      mutant strain GyrB D500N, with the lowest MIC (0.5 MUg/ml), when the standard
      dose was doubled. Moxifloxacin reduced mortality in mice infected with mutant
      strain GyrA A90V with an intermediate MIC (2 MUg/ml). However, it had no impact
      on the mutant strain GyrA D94G with the highest MIC (4 MUg/ml). Our study
      underscores current WHO recommendations to use moxifloxacin when there is
      resistance to early-generation fluoroquinolones such as ofloxacin, restricting
      this recommendation to strains with moxifloxacin MICs of less than or equal to 2
      MUg/ml.

PMID- 20805389
TI  - Reduced expression of the vca0421 gene of Vibrio cholerae O1 results in innate
      resistance to ciprofloxacin.
AB  - A mini-Tn5 insertion into a ciprofloxacin (CIP)-resistant mutant of Vibrio
      cholerae O1 revealed that overexpression of the vca0421 gene, which encodes a
      hypothetical protein, in the CIP-resistant mutant carrying a mutation in the
      quinolone resistance-determining region (QRDR) of the gyrA gene causes
      sensitization to CIP. We propose a new intrinsic mechanism of resistance to
      fluoroquinolones due to the inherently reduced expression of the vca0421 gene in
      V. cholerae O1.

PMID- 20805390
TI  - Mathematical modeling to characterize the inoculum effect.
AB  - Killing by beta-lactams is well known to be reduced against a dense bacterial
      population, commonly known as the inoculum effect. However, the underlying
      mechanism of this phenomenon is not well understood. We proposed a semi
      mechanistic mathematical model to account for the reduced in vitro killing
      observed. Time-kill studies were performed with 4 baseline inocula (ranging from
      approximately 1 * 10(5) to 1 * 10(8) CFU/ml) of Escherichia coli ATCC 25922 (MIC,
      2 mg/liter). Constant but escalating piperacillin concentrations used ranged from
      0.25* to 256* MIC. Serial samples were taken over 24 h to quantify viable
      bacterial burden, and all the killing profiles were mathematically modeled. The
      inoculum effect was attributed to a reduction of effective drug concentration
      available for bacterial killing, which was expressed as a function of the
      baseline inoculum. Biomasses associated with different inocula were examined
      using a colorimetric method. Despite identical drug-pathogen combinations, the
      baseline inoculum had a significant impact on bacterial killing. Our proposed
      mathematical model was unbiased and reasonable in capturing all 28 killing
      profiles collectively (r(2) = 0.88). Biomass was found to be significantly more
      after 24 h with a baseline inoculum of 1 * 10(8) CFU/ml, compared to one where
      the initial inoculum was 1 * 10(5) CFU/ml (P = 0.002). Our results corroborated
      previous observations that in vitro killing by piperacillin was significantly
      reduced against a dense bacterial inoculum. This phenomenon can be reasonably
      captured by our proposed mathematical model, and it may improve prediction of
      bacterial response to various drug exposures in future investigations.

PMID- 20805391
TI  - Synthesis and spectrum of the neoglycoside ACHN-490.
AB  - ACHN-490 is a neoglycoside, or "next-generation" aminoglycoside (AG), that has
      been identified as a potentially useful agent to combat drug-resistant bacteria
      emerging in hospitals and health care facilities around the world. A focused
      medicinal chemistry campaign produced a collection of over 400 sisomicin analogs
      from which ACHN-490 was selected. We tested ACHN-490 against two panels of Gram
      negative and Gram-positive pathogens, many of which harbored AG resistance
      mechanisms. Unlike legacy AGs, ACHN-490 was active against strains expressing
      known AG-modifying enzymes, including the three most common such enzymes found in
      Enterobacteriaceae. ACHN-490 inhibited the growth of AG-resistant
      Enterobacteriaceae (MIC(90), <=4 MUg/ml), with the exception of Proteus mirabilis
      and indole-positive Proteae (MIC(90), 8 MUg/ml and 16 MUg/ml, respectively). ACHN
      490 was more active alone in vitro against Pseudomonas aeruginosa and
      Acinetobacter baumannii isolates with AG-modifying enzymes than against those
      with altered permeability/efflux. The MIC(90) of ACHN-490 against AG-resistant
      staphylococci was 2 MUg/ml. Due to its promising in vitro and in vivo profiles,
      ACHN-490 has been advanced into clinical development as a new antibacterial
      agent.

PMID- 20805392
TI  - Distinct mutation pathways of non-subtype B HIV-1 during in vitro resistance
      selection with nonnucleoside reverse transcriptase inhibitors.
AB  - Studies were conducted to investigate mutation pathways among subtypes A, B, and
      C of human immunodeficiency virus type 1 (HIV-1) during resistance selection with
      nonnucleoside reverse transcriptase inhibitors (NNRTIs) in cell culture under low
      multiplicity of infection (MOI) conditions. The results showed that distinct
      pathways were selected by different virus subtypes under increasing selective
      pressure of NNRTIs. F227C and Y181C were the major mutations selected by MK-4965
      in subtype A and C viruses during resistance selection. With efavirenz (EFV),
      F227C and V106M were the major mutations responsible for viral breakthrough in
      subtype A viruses, whereas a single pathway (G190A/V106M) accounted for mutation
      development in subtype C viruses. Y181C was the dominant mutation in the
      resistance selection with etravirine (ETV) in subtype A, and E138K/H221Y were the
      mutations detected in the breakthrough viruses from subtype C viruses with ETV.
      In subtype B viruses, on the other hand, known NNRTI-associated mutations (e.g.,
      Y181C, P236L, L100I, V179D, and K103N) were selected by the NNRTIs. The
      susceptibility of the subtype A and B mutant viruses to NNRTIs was determined in
      order to gain insight into the potential mechanisms of mutation development.
      Collectively, these results suggest that minor differences may exist in
      conformation of the residues within the NNRTI binding pocket (NNRTIBP) of reverse
      transcriptase (RT) among the three subtypes of viruses. Thus, the interactions
      between NNRTIs and the residues in the NNRTIBPs of different subtypes may not be
      identical, leading to distinct mutation pathways during resistance selection in
      cell culture.

PMID- 20805393
TI  - Prevalence, mutation patterns, and effects on protease inhibitor susceptibility
      of the L76V mutation in HIV-1 protease.
AB  - Patterns of HIV-1 protease inhibitor (PI) resistance-associated mutations (RAMs)
      and effects on PI susceptibility associated with the L76V mutation were studied
      in a large database. Of 20,501 sequences with >=1 PI RAM, 3.2% contained L76V;
      L76V was alone in 0.04%. Common partner mutations included M46I, I54V, V82A,
      I84V, and L90M. L76V was associated with a 2- to 6-fold decrease in
      susceptibility to lopinavir, darunavir, amprenavir, and indinavir and a 7- to 8
      fold increase in susceptibility to atazanavir and saquinavir.

PMID- 20805394
TI  - GES extended-spectrum beta-lactamases in Acinetobacter baumannii isolates in
      Belgium.
AB  - During a PCR-based surveillance study of beta-lactam resistance, 125 multidrug
      resistant (MDR) Acinetobacter baumannii isolates were obtained from 18 hospitals
      in Belgium from January 2008 to December 2009. Nine GES-positive A. baumannii
      isolates were detected at 6 Belgian hospitals. DNA sequencing of the bla(GES)
      genes identified GES-11, GES-12, and a novel variant GES-14, which differs from
      GES-11 by a single amino acid substitution (Gly170Ser). All index isolates were
      travel associated and originated from patients transferred from Turkey (n = 2),
      Egypt (n = 2), and Palestinian territories (Gaza) (n = 2). A nosocomial outbreak
      involving three additional patients occurred in a burn unit at a single hospital.
      No clonal relatedness could be established between the 6 index isolates by pulsed
      field gel electrophoresis (PFGE) analysis. Three different alleles (the plasmid
      located bla(GES-11) and bla(GES-12) and a likely chromosomally located novel
      variant bla(GES-14)) were detected as part of a class 1 integron, also including
      the aac6'Ib and dfrA7 genes. Restriction analysis of plasmids suggests a common
      origin for the plasmids bearing bla(GES-11) and bla(GES-12). Cloning of the
      bla(GES) genes in Escherichia coli identified GES-14 as hydrolyzing imipenem,
      while GES-12 showed the highest specific activity against ceftazidime. This
      report highlights the emergence of various bla(GES-like) genes, especially those
      conferring carbapenem resistance in A. baumannii and its importation in Western
      Europe from Middle Eastern countries.

PMID- 20805396
TI  - A mecA-negative strain of methicillin-resistant Staphylococcus aureus with high
      level beta-lactam resistance contains mutations in three genes.
AB  - We previously generated a ceftobiprole-resistant Staphylococcus aureus strain
      after high inoculum serial passage of a mecA-negative variant of strain COL (R.
      Banerjee, M. Gretes, L. Basuino, N. Strynadka, and H. F. Chambers, Antimicrob.
      Agents Chemother. 52:2089-2096, 2008). Genome resequencing of this strain, CRB,
      revealed that it differs from its parent by five single-nucleotide polymorphisms
      in three genes, specifically, those encoding PBP4, a low-molecular-weight
      penicillin-binding protein, GdpP, a predicted signaling protein, and AcrB, a
      cation multidrug efflux transporter. CRB displayed resistance to a variety of
      beta-lactams but was hypersusceptible to cefoxitin.

PMID- 20805395
TI  - Prevalence of antimicrobial-resistant pathogens in Canadian hospitals: results of
      the Canadian Ward Surveillance Study (CANWARD 2008).
AB  - A total of 5,282 bacterial isolates obtained between 1 January and 31 December 31
      2008, inclusive, from patients in 10 hospitals across Canada as part of the
      Canadian Ward Surveillance Study (CANWARD 2008) underwent susceptibility testing.
      The 10 most common organisms, representing 78.8% of all clinical specimens, were
      as follows: Escherichia coli (21.4%), methicillin-susceptible Staphylococcus
      aureus (MSSA; 13.9%), Streptococcus pneumoniae (10.3%), Pseudomonas aeruginosa
      (7.1%), Klebsiella pneumoniae (6.0%), coagulase-negative
      staphylococci/Staphylococcus epidermidis (5.4%), methicillin-resistant S. aureus
      (MRSA; 5.1%), Haemophilus influenzae (4.1%), Enterococcus spp. (3.3%),
      Enterobacter cloacae (2.2%). MRSA comprised 27.0% (272/1,007) of all S. aureus
      isolates (genotypically, 68.8% of MRSA were health care associated [HA-MRSA] and
      27.6% were community associated [CA-MRSA]). Extended-spectrum beta-lactamase
      (ESBL)-producing E. coli occurred in 4.9% of E. coli isolates. The CTX-M type was
      the predominant ESBL, with CTX-M-15 the most prevalent genotype. MRSA
      demonstrated no resistance to ceftobiprole, daptomycin, linezolid, telavancin,
      tigecycline, or vancomycin (0.4% intermediate intermediate resistance). E. coli
      demonstrated no resistance to ertapenem, meropenem, or tigecycline. Resistance
      rates with P. aeruginosa were as follows: colistin (polymyxin E), 0.8%; amikacin,
      3.5%; cefepime, 7.2%; gentamicin, 12.3%; fluoroquinolones, 19.0 to 24.1%;
      meropenem, 5.6%; piperacillin-tazobactam, 8.0%. A multidrug-resistant (MDR)
      phenotype occurred frequently in P. aeruginosa (5.9%) but uncommonly in E. coli
      (1.2%) and K. pneumoniae (0.9%). In conclusion, E. coli, S. aureus (MSSA and
      MRSA), P. aeruginosa, S. pneumoniae, K. pneumoniae, H. influenzae, and
      Enterococcus spp. are the most common isolates recovered from clinical specimens
      in Canadian hospitals. The prevalence of MRSA was 27.0% (of which genotypically
      27.6% were CA-MRSA), while ESBL-producing E. coli occurred in 4.9% of isolates.
      An MDR phenotype was common in P. aeruginosa.

PMID- 20805397
TI  - In vitro and in vivo antifungal susceptibilities of the Mucoralean fungus
      Cunninghamella.
AB  - We have determined the in vitro activities of amphotericin B (AMB), voriconazole,
      posaconazole (PSC), itraconazole (ITC), ravuconazole, terbinafine, and
      caspofungin against five strains of Cunninghamella bertholletiae and four of
      Cunninghamella echinulata. The best activity was shown by terbinafine against
      both species (MIC range = 0.3 to 0.6 MUg/ml) and PSC against Cunninghamella
      bertholletiae (MIC = 0.5 MUg/ml). We have also evaluated the efficacies of PSC,
      ITC, and AMB in neutropenic and diabetic murine models of disseminated infection
      by Cunninghamella bertholletiae. PSC at 40, 60, or 80 mg/kg of body weight/day
      was as effective as AMB at 0.8 mg/kg/day in prolonging survival and reducing the
      fungal tissue burden in neutropenic mice. PSC at 80 mg/kg/day was more effective
      than AMB at 0.8 mg/kg/day in reducing the fungal load in brain and lung of
      diabetic mice. Histological studies revealed an absence of fungal elements in
      organs of mice treated with either AMB at 0.8 mg/kg/day or PSC at 60 or 80
      mg/kg/day in both models. ITC showed limited efficacy in both models. PSC could
      be a therapeutic option for the treatment of systemic infections caused by
      Cunninghamella bertholletiae.

PMID- 20805398
TI  - In vitro profiling of pramiconazole and in vivo evaluation in Microsporum canis
      dermatitis and Candida albicans vaginitis laboratory models.
AB  - The triazole antifungal pramiconazole (Stiefel, a GSK company) was compared with
      itraconazole, miconazole, and terbinafine in vitro and in vivo. Potent in vitro
      activities against Candida spp. (50% inhibitory concentration [IC50], 0.04 to
      1.83 MUM) and Microsporum and Trichophyton spp. (IC50, 0.15 to 1.34 MUM) were
      obtained but not, however, against other filamentous molds and zygomycetes. In
      the M. canis guinea pig model and C. albicans vulvovaginitis rat model,
      pramiconazole was superior to the reference compounds after oral and topical
      administration.

PMID- 20805399
TI  - Environmental study of azole-resistant Aspergillus fumigatus and other aspergilli
      in Austria, Denmark, and Spain.
AB  - A single mechanism of azole resistance was shown to predominate in clinical and
      environmental Aspergillus fumigatus isolates from the Netherlands, and a link to
      the use of azoles in the environment was suggested. To explore the prevalence of
      azole-resistant A. fumigatus and other aspergilli in the environment in other
      European countries, we collected samples from the surroundings of hospitals in
      Copenhagen, Innsbruck, and Madrid, flowerbeds in an amusement park in Copenhagen,
      and compost bags purchased in Austria, Denmark, and Spain and screened for azole
      resistance using multidish agars with itraconazole, voriconazole, and
      posaconazole. EUCAST method E.DEF 9.1 was used to confirm azole resistance. The
      promoter and entire coding sequence of the cyp51A gene were sequenced to identify
      azole-resistant A. fumigatus isolates. A. fumigatus was recovered in 144 out of
      185 samples (77.8%). Four A. fumigatus isolates from four Danish soil samples
      displayed elevated azole MICs (8%), and all harbored the same TR/L98H mutation of
      cyp51A. One A. lentulus isolate with voriconazole MIC of 4 mg/liter was detected
      in Spain. No azole-resistant aspergilli were detected in compost. Finally, A.
      terreus was present in seven samples from Austria. Multi-azole-resistant A.
      fumigatus is present in the environment in Denmark. The resistance mechanism is
      identical to that of environmental isolates in the Netherlands. No link to
      commercial compost could be detected. In Spain and Austria, only Aspergillus
      species with intrinsic resistance to either azoles or amphotericin B were found.

PMID- 20805400
TI  - Thr202Ala in thyA is a marker for the Latin American Mediterranean lineage of the
      Mycobacterium tuberculosis complex rather than para-aminosalicylic acid
      resistance.
AB  - Single nucleotide polymorphisms (SNPs) involved in the development of resistance
      represent powerful markers for the rapid detection of first- and second-line
      resistance in clinical Mycobacterium tuberculosis complex (MTBC) isolates.
      However, the association between particular mutations and phenotypic resistance
      is not always clear-cut, and phylogenetic SNPs have been misclassified as
      resistance markers in the past. In the present study, we investigated the utility
      of a specific polymorphism in thyA (Thr202Ala) as a marker for resistance to para
      aminosalicyclic acid (PAS). Sixty-three PAS-susceptible MTBC strains comprising
      all major phylogenetic lineages, reference strain H37Rv, and 135 multidrug
      resistant (MDR) strains from Germany (comprising 8 PAS-resistant isolates) were
      investigated for the presence of Thr202Ala. In both strain collections, the
      Thr202Ala SNP was found exclusively in strains of the Latin American
      Mediterranean (LAM) lineage irrespective of PAS resistance. Furthermore, PAS MICs
      (0.5 mg/liter) for selected LAM strains (all containing the SNP) and non-LAM
      strains (not containing the SNP), as well as the results of growth curve analyses
      performed in liquid 7H9 medium in the presence of increasing PAS concentrations
      (0 to 2.0 mg/liter), were identical. In conclusion, our data demonstrate that the
      Thr202Ala polymorphism in thyA is not a valid marker for PAS resistance but,
      instead, represents a phylogenetic marker for the LAM lineage of the M.
      tuberculosis complex. These findings challenge some of the previous understanding
      of PAS resistance and, as a consequence, warrant further in-depth investigations
      of the genetic variation in PAS-resistant clinical isolates and spontaneous
      mutants.

PMID- 20805401
TI  - In vitro mitochondrial toxicity of metacavir, a new nucleoside reverse
      transcriptase inhibitor for treatment of hepatitis B virus.
AB  - Therapy with nucleoside reverse transcriptase inhibitors (NRTIs) can be
      associated with mitochondrial toxicity. In vitro studies have been used to
      predict the predisposition for and characterize the mechanisms causing
      mitochondrial toxicity. Metacavir (PNA) is a novel synthetic nucleoside analog
      for oral administration with potent and specific antiviral activity against
      hepatitis B virus (HBV). We assessed the potential for mitochondrial toxicity of
      PNA in long-term cultures of HepG2 hepatoma cells by measuring mitochondrial
      function (through lactate secretion), levels of mitochondrial DNA (mtDNA), and
      the activities of respiratory-chain complexes I to IV. Exposure of HepG2 cells to
      PNA at concentrations up to 50 MUM for 15 days resulted in no deleterious effect
      on cell proliferation, levels of lactate or mtDNA, or enzyme activities of
      respiratory-chain complexes I to IV. In contrast, dideoxycytosine at 10 MUM and
      zidovudine at 50 MUM have significant effects on cell proliferation, levels of
      lactate and mtDNA, and enzyme activities of respiratory-chain complexes I to IV.
      However, PNA at a supratherapeutic concentration of 250 MUM could result in
      significant alterations in the levels of mtDNA and the activities of respiratory
      chain complex enzymes, revealing evidence of the potential mitochondrial toxicity
      of PNA. In summary, these in vitro results indicate that the potential for PNA to
      interfere with mitochondrial functions is low.

PMID- 20805402
TI  - ABC transporters involved in export of cell surface glycoconjugates.
AB  - Complex glycoconjugates play critical roles in the biology of microorganisms.
      Despite the remarkable diversity in glycan structures and the bacteria that
      produce them, conserved themes are evident in the biosynthesis-export pathways.
      One of the primary pathways involves representatives of the ATP-binding cassette
      (ABC) transporter superfamily. These proteins are responsible for the export of a
      wide variety of cell surface oligo- and polysaccharides in both Gram-positive and
      Gram-negative bacteria. Recent investigations of the structure and function of
      ABC transporters involved in the export of lipopolysaccharide O antigens have
      revealed two fundamentally different strategies for coupling glycan
      polymerization to export. These mechanisms are distinguished by the presence (or
      absence) of characteristic nonreducing terminal modifications on the export
      substrates, which serve as chain termination and/or export signals, and by the
      presence (or absence) of a discrete substrate-binding domain in the nucleotide
      binding domain polypeptide of the ABC transporter. A bioinformatic survey
      examining ABC exporters from known oligo- and polysaccharide biosynthesis loci
      identifies conserved nucleotide-binding domain protein families that correlate
      well with themes in the structures and assembly of glycans. The familial
      relationships among the ABC exporters generate hypotheses concerning the
      biosynthesis of structurally diverse oligo- and polysaccharides, which play
      important roles in the biology of bacteria with different lifestyles.

PMID- 20805403
TI  - Microbe hunting.
AB  - Platforms for pathogen discovery have improved since the days of Koch and
      Pasteur; nonetheless, the challenges of proving causation are at least as
      daunting as they were in the late 1800 s. Although we will almost certainly
      continue to accumulate low-hanging fruit, where simple relationships will be
      found between the presence of a cultivatable agent and a disease, these successes
      will be increasingly infrequent. The future of the field rests instead in our
      ability to follow footprints of infectious agents that cannot be characterized
      using classical microbiological techniques and to develop the laboratory and
      computational infrastructure required to dissect complex host-microbe
      interactions. I have tried to refine the criteria used by Koch and successors to
      prove linkage to disease. These refinements are working constructs that will
      continue to evolve in light of new technologies, new models, and new insights.
      What will endure is the excitement of the chase. Happy hunting!

PMID- 20805405
TI  - Origins and evolution of antibiotic resistance.
AB  - Antibiotics have always been considered one of the wonder discoveries of the 20th
      century. This is true, but the real wonder is the rise of antibiotic resistance
      in hospitals, communities, and the environment concomitant with their use. The
      extraordinary genetic capacities of microbes have benefitted from man's overuse
      of antibiotics to exploit every source of resistance genes and every means of
      horizontal gene transmission to develop multiple mechanisms of resistance for
      each and every antibiotic introduced into practice clinically, agriculturally, or
      otherwise. This review presents the salient aspects of antibiotic resistance
      development over the past half-century, with the oft-restated conclusion that it
      is time to act. To achieve complete restitution of therapeutic applications of
      antibiotics, there is a need for more information on the role of environmental
      microbiomes in the rise of antibiotic resistance. In particular, creative
      approaches to the discovery of novel antibiotics and their expedited and
      controlled introduction to therapy are obligatory.

PMID- 20805404
TI  - Genomic insights into bifidobacteria.
AB  - Since the discovery in 1899 of bifidobacteria as numerically dominant microbes in
      the feces of breast-fed infants, there have been numerous studies addressing
      their role in modulating gut microflora as well as their other potential health
      benefits. Because of this, they are frequently incorporated into foods as
      probiotic cultures. An understanding of their full interactions with intestinal
      microbes and the host is needed to scientifically validate any health benefits
      they may afford. Recently, the genome sequences of nine strains representing four
      species of Bifidobacterium became available. A comparative genome analysis of
      these genomes reveals a likely efficient capacity to adapt to their habitats,
      with B. longum subsp. infantis exhibiting more genomic potential to utilize human
      milk oligosaccharides, consistent with its habitat in the infant gut. Conversely,
      B. longum subsp. longum exhibits a higher genomic potential for utilization of
      plant-derived complex carbohydrates and polyols, consistent with its habitat in
      an adult gut. An intriguing observation is the loss of much of this genome
      potential when strains are adapted to pure culture environments, as highlighted
      by the genomes of B. animalis subsp. lactis strains, which exhibit the least
      potential for a gut habitat and are believed to have evolved from the B. animalis
      species during adaptation to dairy fermentation environments.

PMID- 20805406
TI  - Mobility of plasmids.
AB  - Plasmids are key vectors of horizontal gene transfer and essential genetic
      engineering tools. They code for genes involved in many aspects of microbial
      biology, including detoxication, virulence, ecological interactions, and
      antibiotic resistance. While many studies have decorticated the mechanisms of
      mobility in model plasmids, the identification and characterization of plasmid
      mobility from genome data are unexplored. By reviewing the available data and
      literature, we established a computational protocol to identify and classify
      conjugation and mobilization genetic modules in 1,730 plasmids. This allowed the
      accurate classification of proteobacterial conjugative or mobilizable systems in
      a combination of four mating pair formation and six relaxase families. The
      available evidence suggests that half of the plasmids are nonmobilizable and that
      half of the remaining plasmids are conjugative. Some conjugative systems are much
      more abundant than others and preferably associated with some clades or plasmid
      sizes. Most very large plasmids are nonmobilizable, with evidence of ongoing
      domestication into secondary chromosomes. The evolution of conjugation elements
      shows ancient divergence between mobility systems, with relaxases and type IV
      coupling proteins (T4CPs) often following separate paths from type IV secretion
      systems. Phylogenetic patterns of mobility proteins are consistent with the
      phylogeny of the host prokaryotes, suggesting that plasmid mobility is in general
      circumscribed within large clades. Our survey suggests the existence of
      unsuspected new relaxases in archaea and new conjugation systems in cyanobacteria
      and actinobacteria. Few genes, e.g., T4CPs, relaxases, and VirB4, are at the core
      of plasmid conjugation, and together with accessory genes, they have evolved into
      specific systems adapted to specific physiological and ecological contexts.

PMID- 20805408
TI  - Validity and internal consistency of the international knee documentation
      committee subjective knee evaluation form in children and adolescents.
AB  - BACKGROUND: The International Knee Documentation Committee (IKDC) Subjective Knee
      Evaluation Form (IKDC Knee Form) is a valid, reliable, and responsive measure of
      knee-related symptoms, function, and sports activities in adults. Despite the
      incidence of knee injuries in younger individuals, the measurement
      characteristics of the IKDC Knee Form have not been established. Hypothesis/
      PURPOSE: The purpose of this study was to investigate the validity and internal
      consistency of the IKDC Knee Form in pediatric, adolescent, and young adult
      patients with a variety of knee conditions. The authors hypothesized that the
      IKDC Knee Form would be a valid and consistent measure of knee function in these
      age groups. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2.
      METHODS: The IKDC Knee Form and Pediatric Quality of Life Inventory 4.0 Generic
      Core Scales (PedsQL) physical functioning component were administered to 673
      individuals between 6 and 18 years of age. The internal consistency and validity
      of the IKDC Knee Form were determined for the entire cohort and for age group
      cohorts (pediatric, 6-12 years; adolescent, 13-15 years; young adult, 16-18
      years) using the PedsQL physical functioning component for comparison. RESULTS:
      The results were similar across all age groups. In the original format, internal
      consistency was high and factor analysis showed a single, dominant component
      underlying the item responses for each age group. Items 2, 3, and 6 may
      contribute to measurement error in young individuals. Correlation between the
      IKDC Knee Form and PedsQL physical functioning component score was moderately
      high for the entire cohort (r = .83) and for all age groups (pediatric, r = .84;
      adolescent, r = .84; young adult, r = .79). CONCLUSION: In its current form, the
      IKDC Knee Form is a valid and consistent knee-specific measure of symptoms,
      function, and sports activity in individuals between the ages of 6 and 18 years
      with a variety of knee problems. Further work is needed to establish the
      reliability and responsiveness of the IKDC Knee Form for this age group.

PMID- 20805409
TI  - Influence of the anteromedial and posterolateral bundles of the anterior cruciate
      ligament on external and internal tibiofemoral rotation.

PMID- 20805410
TI  - Tunnel position and relationship to postoperative knee laxity after double-bundle
      anterior cruciate ligament reconstruction with a transtibial technique.

PMID- 20805411
TI  - Give me a break.

PMID- 20805412
TI  - Magnetic resonance imaging evaluation of anterior cruciate ligament
      reconstruction using quadrupled hamstring tendon autografts: comparison of
      remnant bundle preservation and standard technique.
AB  - BACKGROUND: Recently, variations of the remnant bundle preservation technique,
      including selective bundle reconstruction and preservation of the anterior
      cruciate ligament tibial remnant, have produced good outcomes. The authors chose
      to investigate whether remnant bundle preservation in anterior cruciate ligament
      reconstruction would affect the remodeling process without inducing
      complications. HYPOTHESIS: An anterior cruciate ligament reconstruction graft can
      be augmented with a tensioned remnant of the native anterior cruciate ligament
      fibers without increasing the tendency of cyclops lesions. The magnetic resonance
      imaging signal intensity in an anterior cruciate ligament graft using the remnant
      bundle preservation technique would be lower than that using the standard
      technique. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Forty-one
      patients who underwent an anterior cruciate ligament reconstruction using the
      remnant bundle preservation technique with quadrupled hamstring tendon autograft
      were evaluated by magnetic resonance imaging at a mean of 6.3 +/- 0.7 months
      after surgery. The control group included 41 consecutive patients who underwent a
      single-bundle anterior cruciate ligament reconstruction by the standard
      technique. The 2 groups did not differ significantly in gender, age distribution,
      mean time until postoperative magnetic resonance imaging, or other patient
      characteristics. The magnetic resonance imaging evaluation focused on 5
      measurements as follows: (1) dimensions of the anterior cruciate ligament graft,
      (2) signal intensity of the anterior cruciate ligament graft using the
      signal/noise quotient (SNQ) from a region of interest analysis, (3) magnetic
      resonance imaging signal intensity and continuity of the preserved remnant
      bundle, (4) orientation of the anterior cruciate ligament, and (5) tibial tunnel
      placement. RESULTS: The remnant bundle preservation group had a significantly
      larger mean anterior cruciate ligament graft (293.4 mm(2)) than did the standard
      group (219.6 mm(2)) (P < .0001). However, the SNQ values of the anterior cruciate
      ligament graft in the remnant bundle preservation group were not significantly
      lower than those in the standard group in any of the 3 zones. In the remnant
      bundle preservation group, magnetic resonance imaging signals obtained from
      preserved remnant bundles in 35 patients (85%) showed 14 knees with a grade I
      signal (homogeneous low intensity) and 21 knees with a grade II signal (a portion
      of the preserved bundle was edematous). The continuity of remnant bundles in 37
      patients (90%) as determined by magnetic resonance imaging was partial in 20
      patients and complete in 17. The 2 groups did not differ significantly in the
      number of cyclops lesions detected by postoperative magnetic resonance imaging.
      CONCLUSION: After anterior cruciate ligament reconstruction, magnetic resonance
      imaging showed significantly larger anterior cruciate ligament grafts in the
      remnant bundle preservation group than in the standard procedure group, and these
      preserved remnant bundles showed progressive remodeling in the anterior cruciate
      ligament graft with no increase in the incidence of cyclops lesions. To determine
      a clinical advantage for the remnant preservation technique, magnetic resonance
      imaging results such as these must be correlated with clinical findings.

PMID- 20805413
TI  - Tensile and shear loading stability of all-inside meniscal repairs: an in vitro
      biomechanical evaluation.
AB  - BACKGROUND: Most biomechanical studies for evaluation of the structural
      properties of meniscal repairs have been performed in tensile loading scenarios
      perpendicular to the circumferential meniscal fibers. However, meniscal repair
      constructs are also exposed to shear forces parallel to the circumferential
      meniscal fibers during healing, particularly in the midportion of the meniscus.
      HYPOTHESIS: Material properties of meniscal repair devices cannot be extrapolated
      from tensile to shear load scenarios. STUDY DESIGN: Controlled laboratory study.
      METHODS: In 84 harvested and isolated bovine lateral menisci following removal of
      adjacent soft tissue, a standardized vertical lesion was set followed by repair
      using all-inside flexible (FasT-Fix, FasT-Fix AB, RapidLoc) and rigid (Meniscus
      Screw, Meniscus Arrow) meniscal repair devices. Vertical and horizontal 2.0
      Ethibond sutures were used as controls. The repaired meniscal construct was
      tested in a tensile (parallel to the axis of the tested repair device) and shear
      load scenario (perpendicular to the axis of the tested repair device) at 5 mm/min
      and 37 degrees C environmental temperature. Maximum load to failure, stiffness,
      and failure mode were recorded. RESULTS: The absolute load to failure values of
      each repair device in the shear scenario were only marginally different from the
      tensile load scenario. However, the stiffness of several tested devices was
      markedly reduced in the shear scenario. In both scenarios, large differences of
      the load to failure and the stiffness between the implant types up to 5-fold were
      found (P < .05). The failure mode of several all-inside flexible repair devices
      was different in the shear versus tensile load scenario, while the failure mode
      of the rigid systems was similar in both scenarios. CONCLUSION: All-inside
      meniscal repair devices exposed to shear load scenarios have comparable maximum
      loads to failures as tensile load scenarios. However, the stiffness of the
      majority of the flexible meniscal repair implants in a shear load scenario is
      markedly reduced. The applied scenario also affects the failure mode in several
      flexible meniscal repair devices. CLINICAL RELEVANCE: Meniscal repair devices
      with sufficient stiffness and stability against shear loads may be favored for
      meniscal repair, especially within the midportion of the meniscus where shear
      loads occur during healing.

PMID- 20805407
TI  - From structure to function: the ecology of host-associated microbial communities.
AB  - In the past several years, we have witnessed an increased interest in
      understanding the structure and function of the indigenous microbiota that
      inhabits the human body. It is hoped that this will yield novel insight into the
      role of these complex microbial communities in human health and disease. What is
      less appreciated is that this recent activity owes a great deal to the pioneering
      efforts of microbial ecologists who have been studying communities in non-host
      associated environments. Interactions between environmental microbiologists and
      human microbiota researchers have already contributed to advances in our
      understanding of the human microbiome. We review the work that has led to these
      recent advances and illustrate some of the possible future directions for
      continued collaboration between these groups of researchers. We discuss how the
      application of ecological theory to the human-associated microbiota can lead us
      past descriptions of community structure and toward an understanding of the
      functions of the human microbiota. Such an approach may lead to a shift in the
      prevention and treatment of human diseases that involves conservation or
      restoration of the normal community structure and function of the host-associated
      microbiota.

PMID- 20805416
TI  - A versatile role of mammalian target of rapamycin in human dendritic cell
      function and differentiation.
AB  - The mammalian target of rapamycin (mTOR) regulates cell growth and survival and
      exists as rapamycin-sensitive mTOR complex (mTORC) 1 and as rapamycin-insensitive
      mTORC2. Although mTOR is a well-known regulator of diverse immune cells, its
      detailed role in human dendritic cell (DC) function and differentiation is only
      incompletely understood. In this study, we demonstrate divergent roles of mTOR
      during activation and differentiation of myeloid DCs (mDCs) and monocyte-derived
      DCs (moDCs). Inhibition of mTORC1 in mDCs activated with TLR-dependent or 
      independent stimuli increased proinflammatory cytokines and NF-kappaB, whereas IL
      10 and STAT3 were blocked. Rapamycin regulated the costimulatory/surface
      molecules CD86, programmed death ligand-1, and CD25 on mDCs and significantly
      increased the T cell allostimulatory potential of mDCs. In contrast, rapamycin
      suppressed immunostimulatory molecules and the allostimulatory potential of LPS
      stimulated moDCs by an inability to augment NF-kappaB signaling. In
      differentiating moDCs, the PI3K/Akt-dependent mTOR pathway was constitutively
      activated by GM-CSF to induce DC differentiation in an mTORC1-dependent manner.
      Inhibition of mTORC1 or mTORC1/2 during moDC differentiation decreased moDC
      survival and markedly hampered its immunostimulatory phenotype. Analyzing the
      fate of DCs in vivo, we found that kidney transplant patients treated with
      rapamycin displayed an increased immunostimulatory potential of mDCs compared
      with patients treated with calcineurin inhibitors. Furthermore, rapamycin did not
      interfere with mDC differentiation in these patients. Collectively, mTOR exerts
      divergent immunoregulatory functions during DC activation and differentiation
      depending on the DC type that lead to opposing T cell responses, which might be
      of clinical importance in transplantation, cancer, and also for novel vaccination
      strategies.

PMID- 20805415
TI  - Impaired phagocytosis of apoptotic cells by macrophages in chronic granulomatous
      disease is reversed by IFN-gamma in a nitric oxide-dependent manner.
AB  - Immunodeficiency in chronic granulomatous disease (CGD) is well characterized.
      Less understood are exaggerated sterile inflammation and autoimmunity associated
      with CGD. Impaired recognition and clearance of apoptotic cells resulting in
      their disintegration may contribute to CGD inflammation. We hypothesized that
      priming of macrophages (Ms) with IFN-gamma would enhance impaired engulfment of
      apoptotic cells in CGD. Diverse M populations from CGD (gp91(phox)(-/-)) and wild
      type mice, as well as human Ms differentiated from monocytes and promyelocytic
      leukemia PLB-985 cells (with and without mutation of the gp91(phox)),
      demonstrated enhanced engulfment of apoptotic cells in response to IFN-gamma
      priming. Priming with IFN-gamma was also associated with increased uptake of Ig
      opsonized targets, latex beads, and fluid phase markers, and it was accompanied
      by activation of the Rho GTPase Rac. Enhanced Rac activation and phagocytosis
      following IFN-gamma priming were dependent on NO production via inducible NO
      synthase and activation of protein kinase G. Notably, endogenous production of
      TNF-alpha in response to IFN-gamma priming was critically required for inducible
      NO synthase upregulation, NO production, Rac activation, and enhanced
      phagocytosis. Treatment of CGD mice with IFN-gamma also enhanced uptake of
      apoptotic cells by M in vivo via the signaling pathway. Importantly, during acute
      sterile peritonitis, IFN-gamma treatment reduced excess accumulation of apoptotic
      neutrophils and enhanced phagocytosis by CGD Ms. These data support the
      hypothesis that in addition to correcting immunodeficiency in CGD, IFN-gamma
      priming of Ms restores clearance of apoptotic cells and may thereby contribute to
      resolution of exaggerated CGD inflammation.

PMID- 20805417
TI  - Distinct requirements of microRNAs in NK cell activation, survival, and function.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that have recently emerged as
      critical regulators of gene expression within the immune system. In this study,
      we used mice with conditional deletion of Dicer and DiGeorge syndrome critical
      region 8 (Dgcr8) to dissect the roles of miRNAs in NK cell activation, survival,
      and function during viral infection. We developed a system for deletion of either
      Dicer or Dgcr8 in peripheral NK cells via drug-induced Cre activity. We found
      that Dicer- and Dgcr8-deficient NK cells were significantly impaired in survival
      and turnover, and had impaired function of the ITAM-containing activating NK cell
      receptors. We further demonstrated that both Dicer- and Dgcr8-dependent pathways
      were indispensable for the expansion of Ly49H(+) NK cells during mouse
      cytomegalovirus infection. Our data indicate similar phenotypes for Dicer- and
      Dgcr8-deficient NK cells, which strongly suggest that these processes are
      regulated by miRNAs. Thus, our findings indicate a critical role for miRNAs in
      controlling NK cell homeostasis and effector function, with implications for
      miRNAs regulating diverse aspects of NK cell biology.

PMID- 20805418
TI  - Neutralization of IL-9 ameliorates experimental autoimmune encephalomyelitis by
      decreasing the effector T cell population.
AB  - Multiple sclerosis is a CD4(+) T cell-mediated autoimmune disease affecting the
      CNS. Multiple sclerosis and its animal model, experimental autoimmune
      encephalomyelitis (EAE), have been thought to be Th1-mediated diseases. However,
      recent studies provide strong evidence that the major pathogenic T cell subsets
      in EAE are Th17 cells. IL-9, a hematopoietic growth factor, is considered to be a
      mediator of Th17 cells, but the precise mechanisms of its action are largely
      unknown. The present study was designed to investigate the role of IL-9 in
      autoimmune demyelination. IL-9 blockade with anti-IL-9 mAb inhibited the
      development of EAE, reduced the serum levels of IL-17, the CNS mRNA expression of
      IL-17, IL-6, IFN-gamma, and TNF-alpha, and the myelin oligodendrocyte
      glycoprotein (MOG)-induced IL-17, IFN-gamma secretion of lymphocytes.
      Furthermore, anti-IL-9 mAb in culture suppressed IL-17 production of MOG-reactive
      T cells and their potency in adoptive transfer EAE. These findings indicate that
      the protective effect of IL-9 blockade in EAE was likely mediated via inhibition
      of the development of MOG peptide-specific T cells, which in turn led to reduced
      infiltration of T cells into the CNS. Thus, anti-IL-9 mAb treatment may provide
      an effective therapeutic strategy against autoimmune diseases.

PMID- 20805420
TI  - Induction of Th17 cells in the tumor microenvironment improves survival in a
      murine model of pancreatic cancer.
AB  - An important mechanism by which pancreatic cancer avoids antitumor immunity is by
      recruiting regulatory T cells (Tregs) to the tumor microenvironment. Recent
      studies suggest that suppressor Tregs and effector Th17 cells share a common
      lineage and differentiate based on the presence of certain cytokines in the
      microenvironment. Because IL-6 in the presence of TGF-beta has been shown to
      inhibit Treg development and induce Th17 cells, we hypothesized that altering the
      tumor cytokine environment could induce Th17 and reverse tumor-associated immune
      suppression. Pan02 murine pancreatic tumor cells that secrete TGF-beta were
      transduced with the gene encoding IL-6. C57BL/6 mice were injected s.c. with wild
      type (WT), empty vector (EV), or IL-6-transduced Pan02 cells (IL-6 Pan02) to
      investigate the impact of IL-6 secretion in the tumor microenvironment. Mice
      bearing IL-6 Pan02 tumors demonstrated significant delay in tumor growth and
      better overall median survival compared with mice bearing WT or EV Pan02 tumors.
      Immunohistochemical analysis demonstrated an increase in Th17 cells (CD4(+)IL
      23R(+) cells and CD4(+)IL-17(+) cells) in tumors of the IL-6 Pan02 group compared
      with WT or EV Pan02 tumors. The upregulation of IL-17-secreting CD4(+) tumor
      infiltrating lymphocytes was substantiated at the cellular level by flow
      cytometry and ELISPOT assay and mRNA level for retinoic acid-related orphan
      receptor gammat and IL-23R by RT-PCR. Thus, the addition of IL-6 to the tumor
      microenvironment skews the balance toward Th17 cells in a murine model of
      pancreatic cancer. The delayed tumor growth and improved survival suggests that
      induction of Th17 in the tumor microenvironment produces an antitumor effect.

PMID- 20805419
TI  - The detrimental effects of IFN-alpha on vasculogenesis in lupus are mediated by
      repression of IL-1 pathways: potential role in atherogenesis and renal vascular
      rarefaction.
AB  - Systemic lupus erythematosus (SLE) is characterized by increased vascular risk
      due to premature atherosclerosis independent of traditional risk factors. We
      previously proposed that IFN-alpha plays a crucial role in premature vascular
      damage in SLE. IFN-alpha alters the balance between endothelial cell apoptosis
      and vascular repair mediated by endothelial progenitor cells (EPCs) and myeloid
      circulating angiogenic cells (CACs). In this study, we demonstrate that IFN-alpha
      promotes an antiangiogenic signature in SLE and control EPCs/CACs, characterized
      by transcriptional repression of IL-1alpha and beta, IL-1R1, and vascular
      endothelial growth factor A, and upregulation of IL-1R antagonist and the decoy
      receptor IL-1R2. IL-1beta promotes significant improvement in the functional
      capacity of lupus EPCs/CACs, therefore abrogating the deleterious effects of IFN
      alpha. The beneficial effects from IL-1 are mediated, at least in part, by
      increases in EPC/CAC proliferation, by decreases in EPC/CAC apoptosis, and by
      preventing the skewing of CACs toward nonangiogenic pathways. IFN-alpha induces
      STAT2 and 6 phosphorylation in EPCs/CACs, and JAK inhibition abrogates the
      transcriptional antiangiogenic changes induced by IFN-alpha in these cells.
      Immunohistochemistry of renal biopsies from patients with lupus nephritis, but
      not anti-neutrophil cytoplasmic Ab-positive vasculitis, showed this pathway to be
      operational in vivo, with increased IL-1R antagonist, downregulation of vascular
      endothelial growth factor A, and glomerular and blood vessel decreased capillary
      density, compared with controls. Our study introduces a novel putative pathway by
      which type I IFNs may interfere with vascular repair in SLE through repression of
      IL-1-dependent pathways. This could promote atherosclerosis and loss of renal
      function in this disease.

PMID- 20805421
TI  - Coevolution of killer cell Ig-like receptors with HLA-C to become the major
      variable regulators of human NK cells.
AB  - Interactions between HLA class I and killer cell Ig-like receptors (KIRs)
      diversify human NK cell responses. Dominant KIR ligands are the C1 and C2
      epitopes of MHC-C, a young locus restricted to humans and great apes. C1- and C1
      specific KIRs evolved first, being present in orangutan and functionally like
      their human counterparts. Orangutans lack C2 and C2-specific KIRs, but have a
      unique C1+C2-specific KIR that binds equally to C1 and C2. A receptor with this
      specificity likely provided the mechanism by which C2-KIR interaction evolved
      from C1-KIR while avoiding a nonfunctional intermediate, that is, either orphan
      receptor or ligand. Orangutan inhibitory MHC-C-reactive KIRs pair with activating
      receptors of identical avidity and specificity, contrasting with the selective
      attenuation of human activating KIRs. The orangutan C1-specific KIR reacts or
      cross-reacts with all four polymorphic epitopes (C1, C2, Bw4, and A3/11)
      recognized by human KIRs, revealing their structural commonality. Saturation
      mutagenesis at specificity-determining position 44 demonstrates that KIRs are
      inherently restricted to binding just these four epitopes, either individually or
      in combination. This restriction frees most HLA-A and HLA-B variants to be
      dedicated TCR ligands, not subject to conflicting pressures from the NK cell and
      T cell arms of the immune response.

PMID- 20805422
TI  - Inefficient lymph node sensitization during respiratory viral infection promotes
      IL-17-mediated lung pathology.
AB  - Development of bronchus-associated lymphoid tissue has been suggested to enhance
      local antiviral immune responses; however, ectopic lymph node formation often
      corresponds to chronic inflammatory diseases. These studies investigated the role
      of ectopic pulmonary lymph nodes upon respiratory syncytial virus (RSV) infection
      using CCR7-deficient mice, which develop bronchus-associated lymphoid tissue
      early in life. CCR7(-/-) mice exhibited impaired secondary lymph node formation,
      enhanced effector T cell responses and pathogenic mucus production in the lung
      after RSV infection. IL-17 production from CD4 T cells in CCR7(-/-) mice was most
      remarkably enhanced. Wild-type animals reconstituted with CCR7(-/-) bone marrow
      recapitulated the pathogenic lung phenotype in CCR7(-/-) mice, whereas CCR7(-/-)
      animals reconstituted with wild-type bone marrow had normal lymph node
      development, diminished IL-17 production and reduced lung pathology. Mixed bone
      marrow chimeras revealed an alteration of immune responses only in CCR7(-/-) T
      cells, suggesting that impaired trafficking promotes local effector cell
      generation. Lymphotoxin-alpha-deficient mice infected with RSV were used to
      further examine locally induced immune responses and demonstrated increased mucus
      production and amplified cytokine responses in the lung, especially IL-17.
      Neutralization of IL-17 in CCR7(-/-) or in lymphotoxin-alpha-deficient animals
      specifically inhibited mucus hypersecretion and reduced IL-13. Thus, immune cell
      trafficking to secondary lymph nodes is necessary for appropriate cytokine
      responses to RSV as well as modulation of the local environment.

PMID- 20805423
TI  - TCR repertoire, clonal dominance, and pulmonary trafficking of mycobacterium
      specific CD4+ and CD8+ T effector cells in immunity against tuberculosis.
AB  - Clonal responses of Mycobacterium tuberculosis-specific CD4(+) or CD8(+) T
      effector cells producing antituberculosis cytokine IFN-gamma in the context of
      immune protection against tuberculosis remain poorly characterized in humans.
      Utilizing decade-long TCR expertise, we previously developed a useful method to
      isolate clonotypic TCR sequences from Ag-specific IFN-gamma-producing T cells and
      to specifically measure clonotypic TCR frequencies in the T cell pool. In this
      study, we investigated TCR Vbeta repertoires/CDR3 usage, clonal expansion or
      dominance, and pulmonary trafficking or accumulation for purified protein
      deritative (PPD)-specific T effector cells producing IFN-gamma during bacillus
      Calmette-Guerin (BCG) vaccination and subsequent M. tuberculosis challenge of
      macaques. We found that while PPD-specific CD4(+) and CD8(+) T effector clones
      employed diverse TCR Vbeta repertoires, 30-33% of IFN-gamma(+)CD4(+) T cell
      clones from three M. tuberculosis-infected macaques expressed TCR bearing a
      conserved residue leucine in CDR3. Many Ag-specific IFN-gamma(+) CD4(+) and few
      CD8(+) T effector cells emerged as dominant clones during mycobacterial
      infections and underwent major recall expansion after pulmonary M. tuberculosis
      infection of BCG-vaccinated macaques. PPD-specific T cell clones readily
      trafficked to the airway or lung after BCG vaccination or M. tuberculosis
      infection, and some of them continuously accumulated in lungs during M.
      tuberculosis infection even after they became undetectable in the circulation.
      Importantly, remarkable recall expansion and pulmonary accumulation of T effector
      cells coincided with BCG-induced protection against tuberculosis. Thus, rapid
      clonal expansion and pulmonary accumulation of Ag-specific T effector cells
      appear to be one of the immune mechanisms underlying immunity against
      tuberculosis.

PMID- 20805424
TI  - Preprinted standardized orders promote venous thromboembolism prophylaxis
      compared with traditional handwritten orders: an endorsement of standardized
      evidence-based practice.
AB  - The objective was to determine if a standardized process of care--namely,
      standardized evidence-based medical orders (SEBMOs)--improves physician
      compliance with venous thromboembolism (VTE) prophylaxis. A total of 61
      physicians received information about VTE prophylaxis after introduction of an
      admission SEBMO. Hospitalists received enhanced presentations about SEBMOs and
      their value in VTE prevention; specialists did not. Data were analyzed for 2
      cohorts of 249 at-risk patients: one cohort was admitted with SEBMOs and the
      other with handwritten orders. VTE prophylaxis was ordered for 70% (173 of 249)
      of the SEBMO cohort compared with 22% (55 of 249) of patients whose physicians
      handwrote orders (relative risk ratio = 2.97; 95% confidence interval = 2.33
      3.79; P < .0001). Specialists, who did not receive the enhanced education, were
      more likely to use handwritten orders and less likely to comply with prophylaxis
      standards. Standardized orders promote VTE prophylaxis more than handwritten
      orders. More rigorous education is required to promote compliance with evidence
      based standards of medical practice.

PMID- 20805425
TI  - Ticagrelor in the renal dysfunction subgroup: subjugated or substantiated?

PMID- 20805426
TI  - The ecology of stent thrombosis: a view from a sociobiological perspective.

PMID- 20805427
TI  - Time in recurrent ventricular fibrillation and survival after out-of-hospital
      cardiac arrest.
AB  - BACKGROUND: Current resuscitation guidelines (2005 guidelines [G2005]) accelerate
      ventricular fibrillation (VF) recurrence. We investigated whether patients
      resuscitated under G2005 spend more time in VF and have better survival rates
      than patients treated under the 2000 guidelines (G2000). METHODS AND RESULTS: We
      analyzed continuous ECG recordings of out-of-hospital cardiac arrests
      prospectively collected from January 2006 to January 2008. Patients treated
      according to G2000 (n=282) or G2005 (n=240) with VF as initial rhythm were
      included. We measured the total time a patient was in recurrent VF (the sum of
      all intervals from each onset of recurrent VF to each next successful shock) and
      the time a patient was in initial VF (time interval from rescuer arrival to first
      effective shock). The primary outcome measure was neurologically intact survival
      to discharge. The median time in recurrent VF was 2.7 minutes (quartile 1 to 3,
      0.4 to 9.0 minutes) under G2000 versus 4.0 minutes (quartile 1 to 3, 0.2 to 11.6
      minutes) under G2005 (P=0.03). Median time in initial VF was 2.7 minutes
      (quartile 1 to 3, 1.7 to 4.3 minutes) versus 3.9 minutes (quartile 1 to 3, 2.3 to
      6.5 minutes), respectively (P<0.001). Increased time in recurrent VF was
      significantly associated with decreased neurologically intact survival in both
      G2000 use (odds ratio, 0.92; 95% confidence interval, 0.87 to 0.97; P=0.001) and
      G2005 use (odds ratio, 0.94; 95% confidence interval, 0.90 to 0.99; P=0.02).
      Neurologically intact survival decreased significantly with increasing time in
      initial VF under G2000 (odds ratio, 0.86; 95% confidence interval, 0.74 to 0.99;
      P=0.04). This observation was nonexistent in patients treated under G2005.
      Neurologically intact survival was 29% (82 of 282) under G2000 versus 27% (65 of
      240) under G2005 (P=0.61). CONCLUSIONS: With G2005, the time in recurrent VF
      remains associated with worse outcome. Studies of immediate defibrillation for
      recurrent VF are warranted.

PMID- 20805429
TI  - Prevalence, characteristics, and outcomes of patients presenting with cardiogenic
      unilateral pulmonary edema.
AB  - BACKGROUND: Cardiogenic unilateral pulmonary edema (UPE) is a rare entity,
      frequently leading to initial misdiagnosis. We sought to assess the prevalence of
      UPE and to determine its impact on prognosis compared with bilateral pulmonary
      edema. METHODS AND RESULTS: We studied the characteristics and outcomes of
      patients admitted to our institution for cardiogenic pulmonary edema during an 8
      year period. The study population included 869 consecutive patients. The
      prevalence of UPE was 2.1%: 16 right-sided UPE (89%) and 2 left-sided UPE (11%).
      In patients with UPE, blood pressure was significantly lower (P<=0.01), whereas
      noninvasive or invasive ventilation and catecholamines were used more frequently
      (P=0.0004 and P<0.0001, respectively). The prevalence of severe mitral
      regurgitation in patients with bilateral pulmonary edema and UPE was 6% and 100%,
      respectively (P<0.0001). In patients with UPE, use of antibiotic therapy and
      delay in treatment were significantly higher (P<0.0001 and P=0.003,
      respectively). In-hospital mortality was 9%: 39% for UPE versus 8% for bilateral
      pulmonary edema (odds ratio, 6.9; 95% confidence interval, 2.6 to 18; P<0.001).
      In multivariate analysis, unilateral location of pulmonary edema was
      independently related to death whatever the model used (adjusted odds ratio, 6.5;
      95% confidence interval, 1.3 to 32; P=0.021 for model A; and adjusted odds ratio,
      6.8; 95% confidence interval, 1.1 to 41; P=0.037 for model B). CONCLUSIONS:
      Unilateral pulmonary edema represented 2.1% of cardiogenic pulmonary edema in our
      study, usually appeared as an opacity involving the right lung, and was always
      associated with severe mitral regurgitation. Unilateral pulmonary edema is
      related to an independent increased risk of mortality and should be promptly
      recognized to avoid delays in treatment.

PMID- 20805430
TI  - Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal
      function: results from the Platelet Inhibition and Patient Outcomes (PLATO)
      trial.
AB  - BACKGROUND: Reduced renal function is associated with a poorer prognosis and
      increased bleeding risk in patients with acute coronary syndromes and may
      therefore alter the risk-benefit ratio with antiplatelet therapies. In the
      Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor compared with
      clopidogrel reduced the primary composite end point of cardiovascular death,
      myocardial infarction, and stroke at 12 months but with similar major bleeding
      rates. METHODS AND RESULTS: Central laboratory serum creatinine levels were
      available in 15 202 (81.9%) acute coronary syndrome patients at baseline, and
      creatinine clearance, estimated by the Cockcroft Gault equation, was calculated.
      In patients with chronic kidney disease (creatinine clearance <60 mL/min;
      n=3237), ticagrelor versus clopidogrel significantly reduced the primary end
      point to 17.3% from 22.0% (hazard ratio [HR], 0.77; 95% confidence interval [CI],
      0.65 to 0.90) with an absolute risk reduction greater than that of patients with
      normal renal function (n=11 965): 7.9% versus 8.9% (HR, 0.90; 95% CI, 0.79 to
      1.02). In patients with chronic kidney disease, ticagrelor reduced total
      mortality (10.0% versus 14.0%; HR, 0.72; 95% CI, 0.58 to 0.89). Major bleeding
      rates, fatal bleedings, and non-coronary bypass-related major bleedings were not
      significantly different between the 2 randomized groups (15.1% versus 14.3%; HR,
      1.07; 95% CI, 0.88 to 1.30; 0.34% versus 0.77%; HR, 0.48; 95% CI, 0.15 to 1.54;
      and 8.5% versus 7.3%; HR, 1.28; 95% CI, 0.97 to 1.68). The interactions between
      creatinine clearance and randomized treatment on any of the outcome variables
      were nonsignificant. CONCLUSIONS: In acute coronary syndrome patients with
      chronic kidney disease, ticagrelor compared with clopidogrel significantly
      reduces ischemic end points and mortality without a significant increase in major
      bleeding but with numerically more non-procedure-related bleeding. CLINICAL TRIAL
      REGISTRATION: URL:http://www.clinicatrials.gov. Unique identifier: NCT00391872.

PMID- 20805428
TI  - Get With the Guidelines-Stroke performance indicators: surveillance of stroke
      care in the Taiwan Stroke Registry: Get With the Guidelines-Stroke in Taiwan.
AB  - BACKGROUND: Stroke is a leading cause of death around the world. Improving the
      quality of stroke care is a global priority, despite the diverse healthcare
      economies across nations. The American Heart Association/American Stroke
      Association Get With the Guidelines-Stroke program (GWTG-Stroke) has improved the
      quality of stroke care in 790 US academic and community hospitals, with broad
      implications for the rest of the country. The generalizability of GWTG-Stroke
      across national and economic boundaries remains to be tested. The Taiwan Stroke
      Registry, with 30 599 stroke admissions between 2006 and 2008, was used to assess
      the applicability of GWTG-Stroke in Taiwan, which spends ~ 1/10 of what the
      United States does in medical costs per new or recurrent stroke. METHODS AND
      RESULTS: Taiwan Stroke Registry, sponsored by the Taiwan Department of Health,
      engages 39 academic and community hospitals and covers the entire country with 4
      steps of quality control to ensure the reliability of entered data. Five GWTG
      Stroke performance measures and 1 safety indicator are applicable to assess
      Taiwan Stroke Registry quality of stroke care. Demographic and outcome figures
      are comparable between GWTG-Stroke and Taiwan Stroke Registry. Two indicators
      (early and discharge antithrombotics) are close to GWTG-Stroke standards, while 3
      other indicators (intravenous tissue plasminogen activator, anticoagulation for
      atrial fibrillation, lipid-lowering medication) and 1 safety indicator fall
      behind. Preliminary analysis shows that compliance with selected GWTG-Stroke
      guidelines is associated with better outcomes. CONCLUSIONS: Results suggest that
      GWTG-Stroke performance measures, with modification for ethnic factors, can
      become global standards across national and economic boundaries for assessing and
      improving quality of stroke care and outcomes. GWTG-Stroke can be incorporated
      into ongoing stroke registries across nations.

PMID- 20805431
TI  - Late outcomes after carotid artery stenting versus carotid endarterectomy:
      insights from a propensity-matched analysis of the Reduction of Atherothrombosis
      for Continued Health (REACH) Registry.
AB  - BACKGROUND: In patients with carotid artery disease, carotid endarterectomy (CEA)
      and carotid stenting (CAS) are treatment options. Controversy exists as to the
      relative efficacy of the 2 techniques in preventing late events. METHODS AND
      RESULTS: The Reduction of Atherothrombosis for Continued Health (REACH) Registry
      recruited > 68,000 outpatients >= 45 years of age with established
      atherothrombotic disease or >= 3 risk factors for atherothrombosis. Patients with
      CAS or CEA were chosen and followed up prospectively for the occurrence of
      cardiovascular events. Propensity score matching was performed to assemble a
      cohort of patients in whom all baseline covariates would be well balanced.
      Primary outcome was defined as death or stroke at the 2-year follow-up. Secondary
      outcome was stroke or transient ischemic attack. Tertiary outcome was a composite
      of death, myocardial infarction, or stroke and the individual outcomes. Of the 68
      236 patients with atherothrombosis, 3412 patients (5%) had a history of carotid
      artery revascularization (70% asymptomatic carotid stenosis), 1025 (30%) with CAS
      and 2387 (70%) with CEA. Propensity score analyses matched 836 CAS patients with
      836 CEA patients. At the end of 2 years of follow-up, in the propensity score
      matched cohort, CAS was associated with a risk similar to CEA for the primary
      (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.57 to 1.26), secondary
      (HR, 1.20; 95% CI, 0.73 to 1.96), and tertiary (HR, 0.72; 95% CI, 0.51 to 1.01)
      composite outcome, death (HR, 0.63; 95% CI, 0.40 to 1.00), and stroke (HR, 1.48;
      95% CI, 0.79 to 2.80). CONCLUSIONS: In a real-world cohort of patients with a
      history of carotid artery revascularization, CAS was comparable to CEA for late
      outcomes.

PMID- 20805432
TI  - Does black ethnicity influence the development of stent thrombosis in the drug
      eluting stent era?
AB  - BACKGROUND: It has been suggested that black race predicts stent thrombosis (ST)
      after drug-eluting stent implantation. Whether socioeconomic status or comorbid
      conditions confound the contribution of black race to the development of ST is
      unclear. METHODS AND RESULTS: We compared 1594 black patients who underwent drug
      eluting stent implantation with 5642 nonblack patients. Overall, 108 definite STs
      were reported. Multivariable Cox regression analysis was performed with
      adjustment for comorbidities, including median household income as a marker of
      socioeconomic status, to assess the impact that black race may have on the
      development of ST. On univariable analysis, black patients were younger (63.43+/
      12.42 versus 65.15+/-12.59 years; P<0.001) and more likely to have a history of
      hypertension (89.8% versus 81.7%; P<0.001), diabetes mellitus (45.5% versus
      30.8%; P<0.001), chronic renal insufficiency (19.2% versus 10.7%; P<0.001), and
      congestive heart failure (18.7% versus 13.1%; P<0.001). Clopidogrel compliance at
      the time of the ST event was higher in the black than in the nonblack population
      (87.5% versus 77.8%; P=0.068). After multivariable analysis, including adjustment
      for median income and clopidogrel compliance, black race emerged as a strong
      predictor of definite late ST. CONCLUSIONS: Black race is an independent
      predictor of definite drug-eluting stent ST. Because clopidogrel compliance was
      higher in black patients and socioeconomic status was not associated with ST,
      further investigation into the potential mechanisms of this influence of race on
      ST must be pursued.

PMID- 20805433
TI  - Incidence, mechanisms, predictors, and clinical impact of acute and late stent
      malapposition after primary intervention in patients with acute myocardial
      infarction: an intravascular ultrasound substudy of the Harmonizing Outcomes with
      Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial.
AB  - BACKGROUND: The incidence and mechanisms of acute and late stent malapposition
      after primary stent implantation in ST-segment elevation myocardial infarction
      remain unclear. METHODS AND RESULTS: The Harmonizing Outcomes with
      Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial
      was a dual-arm, factorial, randomized trial comparing paclitaxel-eluting stents
      (PES) and otherwise equivalent bare metal stents (BMS) in ST-segment elevation
      myocardial infarction patients. The intravascular ultrasound substudy enrolled
      241 patients with 263 native coronary lesions (201 PES, 62 BMS) with baseline and
      13-month follow-up imaging. Postintervention acute stent malapposition (ASM)
      occurred in 34.3% PES- and 40.3% BMS-treated lesions. Of these, 39.1% PES- and
      40.0% BMS-treated lesions resolved at follow-up, especially within the stent body
      (66.7%); complete resolution was accompanied by a reduction in external elastic
      membrane area. An ASM area >1.2 mm(2) best separated persistent from resolved
      ASM. At follow-up, a higher frequency of late stent malapposition was detected in
      PES-treated lesions (46.8%) mainly because of more late acquired stent
      malapposition (30.8%) compared with BMS-treated lesions. Late acquired stent
      malapposition area correlated to the decrease of peri-stent plaque in the subset
      of lesions without positive remodeling and only to change in external elastic
      membrane in the group with positive remodeling. Independent predictors of late
      acquired stent malapposition were plaque/thrombus protrusion (odds ratio, 5.60;
      95% confidence interval [CI], 2.32 to 13.54) and PES use (odds ratio, 6.32; 95%
      CI, 2.15 to 18.62). CONCLUSIONS: The incidence of ASM was similar in PES- and BMS
      treated lesions, but late acquired stent malapposition was more common in PES
      treated lesions. The reason for resolved ASM was negative remodeling, with larger
      ASM areas separating persistent from resolved ASM. Late acquired stent
      malapposition was due mainly to positive remodeling and plaque/thrombus
      resolution. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00433966.

PMID- 20805434
TI  - Maladaptive aortic properties in children after palliation of hypoplastic left
      heart syndrome assessed by cardiovascular magnetic resonance imaging.
AB  - BACKGROUND: The status of the reconstructed aorta in hypoplastic left heart
      syndrome is considered an important determinant of long-term prognosis.
      Therefore, we assessed the anatomy, elastic properties, and viability of the
      aorta and right ventricular function in patients with hypoplastic left heart
      syndrome by cardiovascular magnetic resonance imaging. METHODS AND RESULTS:
      Cardiovascular magnetic resonance imaging was performed in 40 patients with
      hypoplastic left heart syndrome (age, 6.0+/-2.2 years) and 13 control subjects
      (age, 6.6+/-2.2 years). Aortic dimensions and distensibility were calculated at
      different locations of the aorta using gradient-echo cine imaging at 3.0 T.
      Additionally, pulse-wave velocity, right ventricular ejection fraction, and
      aortic late gadolinium enhancement for viability assessment were measured.
      Compared with control subjects, patients with hypoplastic left heart syndrome had
      increased axial diameters of the aortic root (36.0+/-5.5 versus 24.1+/-2.7
      mm/m(2); P<0.01), ascending aorta (32.0+/-5.0 versus 21.3+/-1.5 mm/m(2); P<0.01),
      and transverse aortic arch (22.7+/-5.2 versus 18.7+/-2.5 mm/m(2); P<0.01). Wall
      distensibility was reduced in the ascending aorta (4.1+/-2.4 versus 13.5+/-7.2
      10(-3) mm Hg(-1); P<0.01) and transverse aortic arch (5.4+/-3.6 versus 10.3+/-3.5
      10(-3) mm Hg(-1); P<0.01). Pulse-wave velocity trended higher in patients
      (P=0.06). Reduced distensibility in the ascending aorta correlated with the
      amount of late gadolinium enhancement in a volume that included the aortic root
      and the ascending aorta (r=-0.72, P<0.01), and both parameters correlated with
      decreased right ventricular ejection fraction. CONCLUSIONS: Adverse aortic
      properties post palliation of hypoplastic left heart syndrome manifest themselves
      by aortic dilatation, decreased distensibility, and increased volume of nonviable
      aortic wall tissue. The negative association between aortic late gadolinium
      enhancement and right ventricular ejection fraction suggests unfavorable aortic
      ventricular coupling. The potential impact of these findings on long-term right
      ventricular function should be evaluated in future studies.

PMID- 20805435
TI  - AACVPR/ACCF/AHA 2010 update: performance measures on cardiac rehabilitation for
      referral to cardiac rehabilitation/secondary prevention services: a report of the
      American Association of Cardiovascular and Pulmonary Rehabilitation and the
      American College of Cardiology Foundation/American Heart Association Task Force
      on Performance Measures (Writing Committee to Develop Clinical Performance
      Measures for Cardiac Rehabilitation).

PMID- 20805436
TI  - Congenitally corrected transposition of the great arteries presenting in a
      nonagenarian.

PMID- 20805437
TI  - Letter by Smolderen and Pelle regarding article, "Efficacy and safety of
      varenicline for smoking cessation in patients with cardiovascular disease: a
      randomized trial".

PMID- 20805440
TI  - Myectomy plus Alfieri technique for outflow tract obstruction in hypertrophic
      cardiomyopathy.

PMID- 20805439
TI  - Cell communications in the heart.

PMID- 20805441
TI  - Heparin induces rat aorta relaxation via integrin-dependent activation of
      muscarinic M3 receptors.
AB  - Previous reports have shown that heparin may promote human hypotension and
      vascular relaxation by elevation of NO levels through unclear mechanisms. We
      hypothesized that endothelial muscarinic M(3) receptor activation mediates the
      heparin-induced vasodilation of rat aortic rings. The experiments were carried
      out using unfractionated heparin extracted from bovine intestinal mucosa, which
      elicited an endothelium and NO-dependent relaxation of aortic segments with
      maximal potency and efficacy (EC(50): 100+/-10 MUmol/L; E(max): 41+/-3%).
      Atropine and 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide inhibitors reduced
      the heparin-dependent relaxation, indicating that M(3) muscarinic receptor is
      involved in this phenomenon. However, no direct binding of heparin to muscarinic
      receptors was observed. More importantly, studies performed using the arginine
      glycine-aspartic acid peptide and 1-(1,1-dimethylethyl)-3-(1-naphthalenyl)-1H
      pyrazolo[3,4-day]pyrimidin-4-amine, an Src family inhibitor, reduced by 51% and
      73% the heparin-dependent relaxation, respectively, suggesting the coupling of
      heparin and M(3) receptor through extracellular matrix molecules and integrin.
      Furthermore, unfractionated heparin induced activation of focal adhesion protein
      kinase, Src, and paxillin. Finally, fluorescence resonance energy transfer
      approach confirmed the interaction of the M(3) receptor to integrin. Taken
      together, these data demonstrate the participation of M(3) receptor and integrin
      in heparin-dependent relaxation of vascular smooth muscle. These results provide
      new insights into the molecular mechanism and potential pharmacological action of
      heparin in vascular physiology.

PMID- 20805445
TI  - What is the value of the 21-gene recurrence score?

PMID- 20805442
TI  - Cytochrome P450 1B1 contributes to angiotensin II-induced hypertension and
      associated pathophysiology.
AB  - Hypertension is the leading cause of cardiovascular diseases, and angiotensin II
      is one of the major components of the mechanisms that contribute to the
      development of hypertension. However, the precise mechanisms for the development
      of hypertension are unknown. Our recent study showing that angiotensin II-induced
      vascular smooth muscle cell growth depends on cytochrome P450 1B1 led us to
      investigate its contribution to hypertension caused by this peptide. Angiotensin
      II was infused via miniosmotic pump into rats (150 ng/kg per minute) or mice
      (1000 MUg/kg per day) for 13 days resulting in increased blood pressure,
      increased cardiac and vascular hypertrophy, increased vascular reactivity to
      vasoconstrictor agents, increased vascular reactive oxygen species production,
      and endothelial dysfunction in both species. The increase in blood pressure and
      associated pathophysiological changes were minimized by the cytochrome P450 1B1
      inhibitor 2,3',4,5'-tetramethoxystilbene in both species and was markedly reduced
      in Cyp1b1(-/-) mice. These data suggest that cytochrome P450 1B1 contributes to
      angiotensin II-induced hypertension and associated pathophysiological changes.
      Moreover, 2,3',4,5'-tetramethoxystilbene, which prevents both cytochrome P450 1B1
      dependent and -independent components of angiotensin II-induced hypertension and
      inhibits associated pathophysiological changes could be clinically useful in the
      treatment of hypertension and associated cardiovascular and inflammatory
      diseases.

PMID- 20805446
TI  - Malignant clear cell sugar tumor of the lung: patient case report.

PMID- 20805447
TI  - Challenge of balancing alcohol intake.

PMID- 20805448
TI  - Prenatal presentation of a metastasizing rhabdoid tumor with homozygous deletion
      of the SMARCB1 gene.

PMID- 20805449
TI  - Rituximab and statins.

PMID- 20805450
TI  - Multivitamin use is not associated with cancer recurrence or survival in patients
      with stage III colon cancer: findings from CALGB 89803.
AB  - PURPOSE: Multivitamin use is widespread in the United States, especially among
      patients with cancer. However, the influence of multivitamin supplementation on
      cancer recurrence and death after a curative resection of colon cancer is
      unknown. PATIENTS AND METHODS: We conducted a prospective, observational study of
      1,038 patients with stage III colon cancer enrolled in a randomized adjuvant
      chemotherapy trial. Patients reported on multivitamin use during and 6 months
      after adjuvant chemotherapy. Patients were observed until March 2009 for disease
      recurrence and death. To minimize bias by occult recurrence, we excluded patients
      who recurred or died within 90 days of their multivitamin assessment. RESULTS:
      Among 1,038 patients, 518 (49.9%) reported multivitamin use during adjuvant
      chemotherapy. Compared with nonusers, the multivariate hazard ratio (HR) for
      disease-free survival was 0.94 (95% CI, 0.77 to 1.15) for patients who used
      multivitamins. Similarly, multivitamin use during adjuvant chemotherapy was not
      significantly associated with recurrence-free survival (multivariate HR, 0.93;
      95% CI, 0.75 to 1.15) or overall survival (multivariate HR 0.92; 95% CI, 0.74 to
      1.16). Multivitamin use reported 6 months after completion of adjuvant
      chemotherapy was also not associated with improved patient outcome, and
      consistent use both during and following adjuvant therapy conferred no benefit.
      Neither an increasing number of tablets nor increasing duration of use before
      cancer diagnosis was associated with cancer recurrence or mortality. Multivitamin
      use also did not improve the rates of grade 3 and higher GI toxicity. CONCLUSION:
      Multivitamin use during and after adjuvant chemotherapy was not significantly
      associated with improved outcomes in patients with stage III colon cancer.

PMID- 20805453
TI  - Molecular anatomy of breast cancer stroma and its prognostic value in estrogen
      receptor-positive and -negative cancers.
AB  - PURPOSE: The purpose of this study was to identify genes enriched in breast
      cancer stroma, assess the stromal gene expression differences between estrogen
      receptor (ER) -positive and -negative cancers, and separately determine their
      prognostic value in these two subtypes of breast cancers. METHODS: We compared
      gene expression profiles of pairs of fine-needle (stroma-poor) and core-needle
      (stroma-rich) biopsies from 37 cancers to identify stroma-associated genes. We
      defined stromal metagenes and tested their prognostic values in 684 node-negative
      patients who received no systemic adjuvant therapy and 259 tamoxifen-treated
      patients. RESULTS: We identified 293 probe sets overexpressed in core biopsies;
      these included five highly coexpressed gene clusters (metagenes) corresponding to
      immune functions and extracellular matrix components. These genes showed
      quantitative and qualitative differences between ER-positive and ER-negative
      cancers. A B-cell/plasma cell metagene showed strong prognostic value in ER
      positive highly proliferative cancers, a lesser prognostic value in ER-negative
      cancers, and no prognostic value in ER-positive cancers with low proliferation.
      The hazard ratio for distant relapse in the lowest compared with the highest
      tertile of the pooled prognostic data set was 4.29 (95% CI, 2.04 to 9.01; P =
      .001) in ER-positive cancers and 3.34 (95% CI, 1.60 to 6.97; P = .001) in ER
      negative cancers. This remained significant in multivariate analysis including
      routine variables and other genomic prognostic scores. As a result of
      quantitative differences in this metagene between ER-positive and ER-negative
      cancers, different thresholds apply in the two subgroups. Other stromal metagenes
      had inconsistent prognostic value. CONCLUSION: Among ER-negative and ER-positive
      highly proliferative cancers, a subset of tumors with high expression of a B
      cell/plasma cell metagene carries a favorable prognosis.

PMID- 20805454
TI  - Prospective evaluation of allogeneic hematopoietic stem-cell transplantation from
      matched related and matched unrelated donors in younger adults with high-risk
      acute myeloid leukemia: German-Austrian trial AMLHD98A.
AB  - PURPOSE: To assess the impact of allogeneic hematopoietic stem-cell
      transplantation (HSCT) from matched related donors (MRDs) and matched unrelated
      donors (MUDs) on outcome in high-risk patients with acute myeloid leukemia (AML)
      within a prospective multicenter treatment trial. PATIENTS AND METHODS: Between
      1998 and 2004, 844 patients (median age, 48 years; range, 16 to 62 years) with
      AML were enrolled onto protocol AMLHD98A that included a risk-adapted treatment
      strategy. High risk was defined by the presence of unfavorable cytogenetics
      and/or by no response to induction therapy. RESULTS: Two hundred sixty-seven
      (32%) of 844 patients were assigned to the high-risk group. Of these 267
      patients, 51 patients (19%) achieved complete remission but had adverse
      cytogenetics, and 216 patients (81%) had no response to induction therapy.
      Allogeneic HSCT was actually performed in 162 (61%) of 267 high-risk patients,
      after a median time of 147 days after diagnosis. Graft sources were as follows:
      MRD (n = 62), MUD (n = 89), haploidentical donor (n = 10), and cord blood (n =
      1). The 5-year overall survival rates were 6.5% (95% CI, 3.1% to 13.6%) for
      patients (n = 105) not proceeding to HSCT and 25.1% (95% CI, 19.1% to 33.0%; from
      date of transplantation) for patients (n = 162) receiving HSCT. Multivariable
      analysis including allogeneic HSCT as a time-dependent covariable revealed that
      allogeneic HSCT significantly improved outcome; there was no difference in
      outcome between allogeneic HSCT from MRD and MUD. CONCLUSION: Allogeneic HSCT in
      younger adults with high-risk AML has a significant beneficial impact on outcome,
      and allogeneic HSCT from MRD and MUD yields similar results.

PMID- 20805455
TI  - Identification of autoantibodies in a patient with testicular cancer and
      concurrent inflammatory bowel disease.

PMID- 20805456
TI  - Prognostic factors in patients with advanced cancer: use of the patient-generated
      subjective global assessment in survival prediction.
AB  - PURPOSE: To determine whether elements of a standard nutritional screening
      assessment are independently prognostic of survival in patients with advanced
      cancer. PATIENTS AND METHODS: A prospective nested cohort of patients with
      metastatic cancer were accrued from different units of a Regional Palliative Care
      Program. Patients completed a nutritional screen on admission. Data included age,
      sex, cancer site, height, weight history, dietary intake, 13 nutrition impact
      symptoms, and patient- and physician-reported performance status (PS). Univariate
      and multivariate survival analyses were conducted. Concordance statistics (c
      statistics) were used to test the predictive accuracy of models based on training
      and validation sets; a c-statistic of 0.5 indicates the model predicts the
      outcome as well as chance; perfect prediction has a c-statistic of 1.0. RESULTS:
      A training set of patients in palliative home care (n = 1,164) was used to
      identify prognostic variables. Primary disease site, PS, short-term weight change
      (either gain or loss), dietary intake, and dysphagia predicted survival in
      multivariate analysis (P < .05). A model including only patients separated by
      disease site and PS with high c-statistics between predicted and observed
      responses for survival in the training set (0.90) and validation set (0.88; n =
      603). The addition of weight change, dietary intake, and dysphagia did not
      further improve the c-statistic of the model. The c-statistic was also not
      altered by substituting physician-rated palliative PS for patient-reported PS.
      CONCLUSION: We demonstrate a high probability of concordance between predicted
      and observed survival for patients in distinct palliative care settings (home
      care, tertiary inpatient, ambulatory outpatient) based on patient-reported
      information.

PMID- 20805457
TI  - Patient information and decision AIDS in oncology: need for communication between
      patients and physicians.

PMID- 20805459
TI  - Diagnosis of bilateral giant adrenal myelolipoma.

PMID- 20805458
TI  - Alcohol consumption and breast cancer recurrence and survival among women with
      early-stage breast cancer: the life after cancer epidemiology study.
AB  - PURPOSE: To examine the association of alcohol consumption after breast cancer
      diagnosis with recurrence and mortality among early-stage breast cancer
      survivors. PATIENTS AND METHODS: Patients included 1,897 LACE study participants
      diagnosed with early-stage breast cancer between 1997 and 2000 and recruited on
      average 2 years postdiagnosis, primarily from the Kaiser Permanente Northern
      California Cancer Registry. Alcohol consumption (ie, wine, beer, and liquor) was
      assessed at cohort entry using a food frequency questionnaire. Cox proportional
      hazards models were used to estimate hazard ratios (HR) and 95% CI with
      adjustment for known prognostic factors. RESULTS: Two hundred ninety-three breast
      cancer recurrences and 273 overall deaths were ascertained after an average
      follow-up of 7.4 years. Nine hundred fifty-eight women (51%) were considered
      drinkers (> 0.5 g/d of alcohol), and the majority drank wine (89%). Drinking >= 6
      g/d of alcohol compared with no drinking was associated with an increased risk of
      breast cancer recurrence (HR, 1.35; 95% CI, 1.00 to 1.83) and death due to breast
      cancer (HR, 1.51; 95% CI, 1.00 to 2.29). The increased risk of recurrence
      appeared to be greater among postmenopausal (HR, 1.51; 95% CI, 1.05 to 2.19) and
      overweight and obese women (HR, 1.60; 95% CI, 1.08 to 2.38). Alcohol intake was
      not associated with all-cause death and possibly associated with decreased risk
      of non-breast cancer death. CONCLUSION: Consuming three to four alcoholic drinks
      or more per week after a breast cancer diagnosis may increase risk of breast
      cancer recurrence, particularly among postmenopausal and overweight/obese women,
      yet the cardioprotective effects of alcohol on non-breast cancer death were
      suggested.

PMID- 20805460
TI  - Cystoid macular edema secondary to nab-paclitaxel therapy.

PMID- 20805461
TI  - Case report: Celiac disease masquerading as bone metastasis in a 29-year-old
      woman.

PMID- 20805462
TI  - Abiraterone acetate is well tolerated without concomitant use of corticosteroids.

PMID- 20805463
TI  - Impact of hospice disenrollment on health care use and medicare expenditures for
      patients with cancer.
AB  - PURPOSE: Patients with cancer represent the largest diagnostic group of hospice
      users, with 560,000 referred for hospice in 2008. Oncologists rely on hospice
      teams to provide care for patients who have completed disease-directed treatment
      and desire to remain at home. However, 11% to 15% of hospice users disenroll from
      hospice, and little is known about their health care use and Medicare
      expenditures. PATIENTS AND METHODS: We used Surveillance, Epidemiology and End
      Results-Medicare data for hospice users who died as a result of cancer between
      1998 and 2002 (N = 90,826) to compare rates of hospitalization, emergency
      department, and intensive care unit admission and hospital death for hospice
      disenrollees and those who remained with hospice until death. We also compared
      per-day and total Medicare expenditures across the two groups. RESULTS: Patients
      with cancer who disenrolled from hospice were more likely to be hospitalized
      (39.8% v 1.6%; P < .001), more likely to be admitted to the emergency department
      (33.9% v 3.1%; P < .001) or intensive care unit (5.7% v 0.1%; P < .001), and more
      likely to die in the hospital (9.6% v 0.2%; P < .001). Patients who disenrolled
      from hospice died a median of 24 days following disenrollment, suggesting that
      the reason for hospice disenrollment was not improved health. In multivariable
      analyses, hospice disenrollees incurred higher per-day Medicare expenditures than
      patients who remained with hospice until death (higher per-day expenditures of
      $124; P < .001). CONCLUSION: Hospice disenrollment is a marker for higher health
      care use and expenditures for care. Strategies to manage a patient's care and
      support family caregivers following hospice disenrollment may be beneficial and
      should be explored.

PMID- 20805464
TI  - Structure and inhibition of herpesvirus DNA packaging terminase nuclease domain.
AB  - During viral replication, herpesviruses package their DNA into the procapsid by
      means of the terminase protein complex. In human cytomegalovirus (herpesvirus 5),
      the terminase is composed of subunits UL89 and UL56. UL89 cleaves the long DNA
      concatemers into unit-length genomes of appropriate length for encapsidation. We
      used ESPRIT, a high-throughput screening method, to identify a soluble purifiable
      fragment of UL89 from a library of 18,432 randomly truncated ul89 DNA constructs.
      The purified protein was crystallized and its three-dimensional structure was
      solved. This protein corresponds to the key nuclease domain of the terminase and
      shows an RNase H/integrase-like fold. We demonstrate that UL89-C has the capacity
      to process the DNA and that this function is dependent on Mn(2+) ions, two of
      which are located at the active site pocket. We also show that the nuclease
      function can be inactivated by raltegravir, a recently approved anti-AIDS drug
      that targets the HIV integrase.

PMID- 20805465
TI  - Chk1 promotes replication fork progression by controlling replication initiation.
AB  - DNA replication starts at initiation sites termed replication origins. Metazoan
      cells contain many more potential origins than are activated (fired) during each
      S phase. Origin activation is controlled by the ATR checkpoint kinase and its
      downstream effector kinase Chk1, which suppresses origin firing in response to
      replication blocks and during normal S phase by inhibiting the cyclin-dependent
      kinase Cdk2. In addition to increased origin activation, cells deficient in Chk1
      activity display reduced rates of replication fork progression. Here we
      investigate the causal relationship between increased origin firing and reduced
      replication fork progression. We use the Cdk inhibitor roscovitine or RNAi
      depletion of Cdc7 to inhibit origin firing in Chk1-inhibited or RNAi-depleted
      cells. We report that Cdk inhibition and depletion of Cdc7 can alleviate the slow
      replication fork speeds in Chk1-deficient cells. Our data suggest that increased
      replication initiation leads to slow replication fork progression and that Chk1
      promotes replication fork progression during normal S phase by controlling
      replication origin activity.

PMID- 20805466
TI  - Remote sensing alone is insufficient for quantifying changes in forest cover.

PMID- 20805468
TI  - Refined LexA transactivators and their use in combination with the Drosophila
      Gal4 system.
AB  - The use of binary transcriptional systems offers many advantages for
      experimentally manipulating gene activity, as exemplified by the success of the
      Gal4/UAS system in Drosophila. To expand the number of applications, a second
      independent transactivator (TA) is desirable. Here, we present the optimization
      of an additional system based on LexA and show how it can be applied. We
      developed a series of LexA TAs, selectively suppressible via Gal80, that exhibit
      high transcriptional activity and low detrimental effects when expressed in vivo.
      In combination with Gal4, an appropriately selected LexA TA permits to program
      cells with a distinct balance and independent outputs of the two TAs. We
      demonstrate how the two systems can be combined for manipulating communicating
      cell populations, converting transient tissue-specific expression patterns into
      heritable, constitutive activities, and defining cell territories by intersecting
      TA expression domains. Finally, we describe a versatile enhancer trap system that
      allows swapping TA and generating mosaics composed of Gal4 and LexA TA-expressing
      cells. The optimized LexA system facilitates precise analyses of complex
      biological phenomena and signaling pathways in Drosophila.

PMID- 20805469
TI  - Insulin-like growth factor 1 treatment extends longevity in a mouse model of
      human premature aging by restoring somatotroph axis function.
AB  - Zmpste24 (also called FACE-1) is a metalloproteinase involved in the maturation
      of lamin A, an essential component of the nuclear envelope. Zmpste24-deficient
      mice exhibit multiple defects that phenocopy human accelerated aging processes
      such as Hutchinson-Gilford progeria syndrome. In this work, we report that
      progeroid Zmpste24(-/-) mice present profound transcriptional alterations in
      genes that regulate the somatotroph axis, together with extremely high
      circulating levels of growth hormone (GH) and a drastic reduction in plasma
      insulin-like growth factor 1 (IGF-1). We also show that recombinant IGF-1
      treatment restores the proper balance between IGF-1 and GH in Zmpste24(-/-) mice,
      delays the onset of many progeroid features, and significantly extends the
      lifespan of these progeroid animals. Our findings highlight the importance of
      IGF/GH balance in longevity and may be of therapeutic interest for devastating
      human progeroid syndromes associated with nuclear envelope abnormalities.

PMID- 20805471
TI  - Repression of Wnt signaling by a Fer-type nonreceptor tyrosine kinase.
AB  - The Wnt signaling pathway must be properly modulated to ensure an appropriate
      output: pathological conditions result from either insufficient or excessive
      levels of Wnt signal. For example, hyperactivation of the Wnt pathway is
      associated with various cancers and subnormal Wnt signaling can lead to increased
      invasiveness of tumor cells. We found that the Caenorhabditis elegans ortholog of
      the Fer nonreceptor tyrosine kinase, FRK-1, limits Wnt signaling by preventing
      the adhesion complex-associated beta-catenin, HMP-2, from participating in Wnt
      dependent specification of the endoderm during embryogenesis. Removal of FRK-1
      function results in relocalization of HMP-2 to the nucleus of epidermal cells,
      and allows it to substitute for WRM-1, the nuclear beta-catenin that normally
      transduces the Wnt signal during endoderm development. APR-1, the C. elegans APC
      ortholog, is similarly required to prevent HMP-2 relocalization and keeps it from
      participating in Wnt signal transduction; this finding partially explains the
      paradoxical observation that APR-1 acts either negatively or positively in Wnt
      signaling, depending on context. The apparent hyperactivation of the Wnt response
      in the absence of FRK-1 leads to hyperproliferation in the endoderm, as is also
      seen when WRM-1 is overexpressed in wild-type embryos. The specification and
      proliferation activities of Wnt signaling are separable: although the Tcf/Lef
      factor POP-1 acts in Wnt-dependent endoderm specification, it is not apparently
      required for hyperproliferation resulting from excessive Wnt signaling. These
      findings highlight a role for a Fer-type kinase in setting the proper levels of
      Wnt signaling and demonstrate the importance of this modulation in ensuring
      appropriate cell division.

PMID- 20805472
TI  - Major increase in human monkeypox incidence 30 years after smallpox vaccination
      campaigns cease in the Democratic Republic of Congo.
AB  - Studies on the burden of human monkeypox in the Democratic Republic of the Congo
      (DRC) were last conducted from 1981 to 1986. Since then, the population that is
      immunologically naive to orthopoxviruses has increased significantly due to
      cessation of mass smallpox vaccination campaigns. To assess the current risk of
      infection, we analyzed human monkeypox incidence trends in a monkeypox-enzootic
      region. Active, population-based surveillance was conducted in nine health zones
      in central DRC. Epidemiologic data and biological samples were obtained from
      suspected cases. Cumulative incidence (per 10,000 population) and major
      determinants of infection were compared with data from active surveillance in
      similar regions from 1981 to 1986. Between November 2005 and November 2007, 760
      laboratory-confirmed human monkeypox cases were identified in participating
      health zones. The average annual cumulative incidence across zones was 5.53 per
      10,000 (2.18-14.42). Factors associated with increased risk of infection
      included: living in forested areas, male gender, age < 15, and no prior smallpox
      vaccination. Vaccinated persons had a 5.2-fold lower risk of monkeypox than
      unvaccinated persons (0.78 vs. 4.05 per 10,000). Comparison of active
      surveillance data in the same health zone from the 1980s (0.72 per 10,000) and
      2006-07 (14.42 per 10,000) suggests a 20-fold increase in human monkeypox
      incidence. Thirty years after mass smallpox vaccination campaigns ceased, human
      monkeypox incidence has dramatically increased in rural DRC. Improved
      surveillance and epidemiological analysis is needed to better assess the public
      health burden and develop strategies for reducing the risk of wider spread of
      infection.

PMID- 20805473
TI  - Functional comparison of the effects of TARPs and cornichons on AMPA receptor
      trafficking and gating.
AB  - Glutamate receptors of the AMPA subtype (AMPARs) mediate fast synaptic
      transmission in the brain. These ionotropic receptors rely on auxiliary subunits
      known as transmembrane AMPAR regulatory proteins (TARPs) for both trafficking and
      gating. Recently, a second family of AMPAR binding proteins, referred to as
      cornichons, were identified and also proposed to function as auxiliary subunits.
      Cornichons are transmembrane proteins that modulate AMPAR function in expression
      systems much like TARPs. In the present study we compare the role of cornichons
      in controlling AMPA receptor function in neurons and HEK cells to that of TARPs.
      Cornichons mimic some, but not all, of the actions of TARPs in HEK cells; their
      role in neurons, however, is more limited. Although expressed cornichons can
      affect the trafficking of AMPARs, they were not detected on the surface of
      neurons and failed to alter the kinetics of endogenous AMPARs. This neuronal role
      is more consistent with that of an endoplasmic reticulum (ER) chaperone rather
      than a bona fide auxiliary subunit.

PMID- 20805474
TI  - Isolation and killing of candidate chronic myeloid leukemia stem cells by
      antibody targeting of IL-1 receptor accessory protein.
AB  - Chronic myeloid leukemia (CML) is genetically characterized by the Philadelphia
      (Ph) chromosome, formed through a reciprocal translocation between chromosomes 9
      and 22 and giving rise to the constitutively active tyrosine kinase P210
      BCR/ABL1. Therapeutic strategies aiming for a cure of CML will require full
      eradication of Ph chromosome-positive (Ph(+)) CML stem cells. Here we used gene
      expression profiling to identify IL-1 receptor accessory protein (IL1RAP) as up
      regulated in CML CD34(+) cells and also in cord blood CD34(+) cells as a
      consequence of retroviral BCR/ABL1 expression. To test whether IL1RAP expression
      distinguishes normal (Ph(-)) and leukemic (Ph(+)) cells within the CML
      CD34(+)CD38(-) cell compartment, we established a unique protocol for conducting
      FISH on small numbers of sorted cells. By using this method, we sorted cells
      directly into drops on slides to investigate their Ph-chromosome status.
      Interestingly, we found that the CML CD34(+)CD38(-)IL1RAP(+) cells were Ph(+),
      whereas CML CD34(+)CD38(-)IL1RAP(-) cells were almost exclusively Ph(-). By
      performing long-term culture-initiating cell assays on the two cell populations,
      we found that Ph(+) and Ph(-) candidate CML stem cells could be prospectively
      separated. In addition, by generating an anti-IL1RAP antibody, we provide proof
      of concept that IL1RAP can be used as a target on CML CD34(+)CD38(-) cells to
      induce antibody-dependent cell-mediated cytotoxicity. This study thus identifies
      IL1RAP as a unique cell surface biomarker distinguishing Ph(+) from Ph(-)
      candidate CML stem cells and opens up a previously unexplored avenue for therapy
      of CML.

PMID- 20805475
TI  - Elr-type proteins protect Xenopus Dead end mRNA from miR-18-mediated clearance in
      the soma.
AB  - Segregation of the future germ line defines a crucial cell fate decision during
      animal development. In Xenopus, germ cells are specified by inheritance of
      vegetally localized maternal determinants, including a group of specific mRNAs.
      Here, we show that the vegetal localization elements (LE) of Xenopus Dead end
      (XDE) and of several other germ-line-specific, vegetally localized transcripts
      mediate germ cell-specific stabilization and somatic clearance of microinjected
      reporter mRNA in Xenopus embryos. The part of XDE-LE critical for somatic RNA
      clearance exhibits homology to zebrafish nanos1 and appears to be targeted by
      Xenopus miR-18 for somatic mRNA clearance. Xenopus Elr-type proteins of the
      vegetal localization complex can alleviate somatic RNA clearance of microinjected
      XDE-LE and endogenous XDE mRNA. ElrB1 synergizes with Xenopus Dead end protein in
      the stabilization of XDE-LE mRNA. Taken together, our findings unveil a
      functional link of vegetal mRNA localization and the protection of germ-line
      mRNAs from somatic clearance.

PMID- 20805476
TI  - In utero exposure to dioxin causes neocortical dysgenesis through the actions of
      p27Kip1.
AB  - Dioxins have been reported to exert various adverse effects, including cell-cycle
      dysregulation in vitro and impairment of spatial learning and memory after in
      utero exposure in rodents. Furthermore, children born to mothers who are exposed
      to dioxin analogs polychlorinated dibenzofurans or polychlorinated biphenyls have
      developmental impairments in cognitive functions. Here, we show that in utero
      exposure to dioxins in mice alters differentiation patterns of neural progenitors
      and leads to decreased numbers of non-GABAergic neurons and thinner deep
      neocortical layers. This reduction in number of non-GABAergic neurons is assumed
      to be caused by accumulation of cyclin-dependent kinase inhibitor p27(Kip1) in
      nuclei of neural progenitors. Lending support to this presumption, mice lacking
      p27(Kip1) are not susceptible to in utero dioxin exposure. These results show
      that environmental pollutants may affect neocortical histogenesis through
      alterations of functions of specific gene(s)/protein(s) (in our case, dioxins),
      exerting adverse effects by altering functions of p27(Kip1).

PMID- 20805477
TI  - Membrane-shaping host reticulon proteins play crucial roles in viral RNA
      replication compartment formation and function.
AB  - Positive-strand RNA viruses replicate their genomes on membranes with virus
      induced rearrangements such as single- or double-membrane vesicles, but the
      mechanisms of such rearrangements, including the role of host proteins, are
      poorly understood. Brome mosaic virus (BMV) RNA synthesis occurs in ~70 nm,
      negatively curved endoplasmic reticulum (ER) membrane invaginations induced by
      multifunctional BMV protein 1a. We show that BMV RNA replication is inhibited 80
      90% by deleting the reticulon homology proteins (RHPs), a family of membrane
      shaping proteins that normally induce and stabilize positively curved peripheral
      ER membrane tubules. In RHP-depleted cells, 1a localized normally to perinuclear
      ER membranes and recruited the BMV 2a(pol) polymerase. However, 1a failed to
      induce ER replication compartments or to recruit viral RNA templates. Partial RHP
      depletion allowed formation of functional replication vesicles but reduced their
      diameter by 30-50%. RHPs coimmunoprecipitated with 1a and 1a expression
      redirected >50% of RHPs from peripheral ER tubules to the interior of BMV-induced
      RNA replication compartments on perinuclear ER. Moreover, RHP-GFP fusions
      retained 1a interaction but shifted 1a-induced membrane rearrangements from
      normal vesicles to double membrane layers, a phenotype also induced by excess 1a
      interacting 2a(pol). Thus, RHPs interact with 1a, are incorporated into RNA
      replication compartments, and are required for multiple 1a functions in
      replication compartment formation and function. The results suggest possible RHP
      roles in the bodies and necks of replication vesicles.

PMID- 20805478
TI  - Enhancement of antigen-specific Treg vaccination in vivo.
AB  - The conversion of naive T cells into Treg can be achieved in vivo by delivery of
      antigen under subimmunogenic conditions. Here we have examined several drugs for
      their ability to enhance the conversion process in vivo and have found that the
      rapamycin analog everolimus potently enhances Treg conversion by interfering with
      T-cell costimulation, reducing cell division and thereby activation of DNA
      methyltransferase 1 as well as by reducing T-cell activation through the ATP
      gated P2*7 receptor controlling Ca2(+) influx. The resulting Tregs exhibit
      increased stability of Foxp3 expression even when generated in TGFbeta-containing
      media in vitro. Thus the mammalian target of rapamycin (mTOR) inhibitor
      everolimus in addition to inhibiting immune responses enhances Treg conversion by
      several distinct pathways. The converted Tregs can be further expanded by
      injection of IL-2/IL-2ab complexes. These complexes also increase the number of
      CD25(+)Foxp3(-) cells that, however, do not represent cytokine secreting effector
      cells but anergic cells, some of which can secrete IL-10 and can themselves be
      considered regulatory T cells as well. The combined use of everolimus and IL-2/IL
      2ab complexes in vivo makes it feasible to achieve highly effective antigen
      driven conversion of naive T cells into Treg and their expansion in vivo and
      thereby the described protocols constitute important tools to achieve
      immunological tolerance by Treg vaccination.

PMID- 20805479
TI  - An unusual dinosaur from the Late Cretaceous of Romania and the island rule.

PMID- 20805480
TI  - A transmembrane formin nucleates subapical actin assembly and controls tip
      focused growth in pollen tubes.
AB  - Pollen tubes are highly polarized plant cells specialized in delivering sperm for
      fertilization. Pollen tube growth is rapid, occurs exclusively at the tip, and
      can reach distances thousands of times the diameter of the pollen grain without
      cell division, thus representing an excellent model system for studying
      asymmetric cell growth. In flowering plants, pollen tube growth is dependent on
      the actin cytoskeleton, which supports an efficient vesicle trafficking system to
      deliver membrane and cell-wall materials to the tube tip. A highly dynamic
      subapical actin structure and an apical vesicular zone are known to be critical
      for the tip-growth process. How this apical organization is maintained, how the
      subapical actin structure is assembled, and direct evidence for its functional
      coupling with tip growth remain to be established. Here, we show that a tip
      located, cell membrane-anchored actin-nucleating protein, the Arabidopsis formin
      homology5 (FH5), stimulates actin assembly from the subapical membrane, provides
      actin filaments for vesicular trafficking to the apical dome, and mediates
      assembly of the subapical actin structure. Moreover, FH5-expressing pollen tubes
      provided a unique opportunity to demonstrate that assembly of the subapical actin
      structure is concomitant with the acquisition of rapid tip growth, providing
      further support for their functional coupling. Together, our results show that
      FH5 plays a pivotal role in establishing the subapical actin and apical vesicular
      organization critical for tip-focused growth in pollen tubes.

PMID- 20805481
TI  - Image-matching during ant navigation occurs through saccade-like body turns
      controlled by learned visual features.
AB  - Visual memories of landmarks play a major role in guiding the habitual foraging
      routes of ants and bees, but how these memories engage visuo-motor control
      systems during guidance is poorly understood. We approach this problem through a
      study of image matching, a navigational strategy in which insects reach a
      familiar place by moving so that their current retinal image transforms to match
      a memorized snapshot of the scene viewed from that place. Analysis of how
      navigating wood ants correct their course when close to a goal reveals a
      significant part of the mechanism underlying this transformation. Ants followed a
      short route to an inconspicuous feeder positioned at a fixed distance from a
      vertical luminance edge. They responded to an unexpected jump of the edge by
      turning to face the new feeder position specified by the edge. Importantly, the
      initial speed of the turn increased linearly with the turn's amplitude. This
      correlation implies that the ants' turns are driven initially by their prior
      calculation of the angular difference between the current retinal position of the
      edge and its desired position in their memorized view. Similar turns keep ants to
      their path during unperturbed routes. The neural circuitry mediating image
      matching is thus concerned not only with the storage of views, but also with
      making exact comparisons between the retinal positions of a visual feature in a
      memorized view and of the same feature in the current retinal image.

PMID- 20805482
TI  - Spontaneous EEG oscillations reveal periodic sampling of visual attention.
AB  - An important effect of sustained attention is the facilitation of perception.
      Although the term "sustained" suggests that this beneficial effect endures
      continuously as long as something is attended, we present electrophysiological
      evidence that perception at attended locations is actually modulated
      periodically. Subjects detected brief light flashes that were presented
      peripherally at locations that were either attended or unattended. We analyzed
      the correlation between detection performance for attended and unattended stimuli
      and the phase of ongoing EEG oscillations, which relate to subsecond fluctuations
      of neuronal excitability. Although on average, detection performance was improved
      by attention--indicated by reduced detection thresholds at attended locations--we
      found that detection performance for attended stimuli actually fluctuated over
      time along with the phase of spontaneous oscillations in the (~7 Hz) frequency
      band just before stimulus onset. This fluctuation was absent for unattended
      stimuli. This pattern of results suggests that "sustained" attention in fact
      exerts its facilitative effect on perception in a periodic fashion.

PMID- 20805483
TI  - Visual motion aftereffect from understanding motion language.
AB  - Do people spontaneously form visual mental images when understanding language,
      and if so, how truly visual are these representations? We test whether processing
      linguistic descriptions of motion produces sufficiently vivid mental images to
      cause direction-selective motion adaptation in the visual system (i.e., cause a
      motion aftereffect illusion). We tested for motion aftereffects (MAEs) following
      explicit motion imagery, and after processing literal or metaphorical motion
      language (without instructions to imagine). Intentionally imagining motion
      produced reliable MAEs. The aftereffect from processing motion language gained
      strength as people heard more and more of a story (participants heard motion
      stories in four installments, with a test after each). For the last two story
      installments, motion language produced reliable MAEs across participants.
      Individuals differed in how early in the story this effect appeared, and this
      difference was predicted by the strength of an individual's MAE from imagining
      motion. Strong imagers (participants who showed the largest MAEs from imagining
      motion) were more likely to show an MAE in the course of understanding motion
      language than were weak imagers. The results demonstrate that processing language
      can spontaneously create sufficiently vivid mental images to produce direction
      selective adaptation in the visual system. The timecourse of adaptation suggests
      that individuals may differ in how efficiently they recruit visual mechanisms in
      the service of language understanding. Further, the results reveal an intriguing
      link between the vividness of mental imagery and the nature of the processes and
      representations involved in language understanding.

PMID- 20805484
TI  - Social interaction modulates autonomic, inflammatory, and depressive-like
      responses to cardiac arrest and cardiopulmonary resuscitation.
AB  - Psychological factors, including depression and social isolation, are important
      determinants of cardiovascular health. The current study uses a well-validated
      mouse model of cardiac arrest/cardiopulmonary resuscitation (CA/CPR) to examine
      the effect of social environment on several pathophysiological and behavioral
      responses to cerebral ischemia. Male experimental mice were either housed in
      pairs with an ovariectomized female or socially isolated for the duration of the
      experiment. Cardiac arrest increased the mRNA expression of the proinflammatory
      cytokines TNF-alpha, IL-1beta, and IL-6, as well as the microglia marker MAC-1;
      expression of each of these factors, except IL-6, was further increased among
      socially isolated mice. Furthermore, socially isolated animals exposed to the
      CA/CPR procedure displayed significantly higher levels of neuronal cell death and
      microglia staining within the hippocampus at 7 d following surgery. Social
      isolation also exacerbated CA/CPR-induced depressive-like behavior and cardiac
      autonomic dysregulation. In the absence of ischemic damage, social environment
      had no significant effect on the expression of neuronal cell death, autonomic
      cardiac control, or behavior. Together, these data suggest that social factors
      influence the pathophysiological trajectory following cardiac arrest.

PMID- 20805485
TI  - Ancient DNA reveals extreme egg morphology and nesting behavior in New Zealand's
      extinct moa.
AB  - New Zealand's extinct flightless moa radiated rapidly into a large number of
      morphologically diverse species, which produced an equally large range of egg
      morphologies. The exact number of moa species, as well as the characteristics of
      the eggs they laid, remains contentious. Moreover, like most extinct species, we
      understand little about their nesting and incubation habits. We used a modified
      ancient DNA extraction procedure to recover exogenous mitochondrial and nuclear
      DNA from the inside and outside surfaces of moa eggs. We used sequences from the
      inside of 69 eggshells to directly assign these remains to seven of the 10
      currently recognized moa species. In addition we were able to assign, to the
      species level, six of the rare reconstructed "whole" eggs. These molecular
      results enabled us to identify two distinct lineages within the genus
      Euryapteryx. Members of these lineages differed in eggshell thickness, with one
      lineage being characterized by a relatively thin eggshell. Unexpectedly, several
      thin-shelled eggs were also shown to belong to the heaviest moa of the genera
      Dinornis, Euryapteryx and Emeus, making these, to our knowledge, the most fragile
      of all avian eggs measured to date. Moreover, sex-specific DNA recovered from the
      outer surfaces of eggshells belonging to species of Dinornis and Euryapteryx
      suggest that these very thin eggs were likely to have been incubated by the
      lighter males. The thin nature of the eggshells of these larger species of moa,
      even if incubated by the male, suggests that egg breakage in these species would
      have been common if the typical contact method of avian egg incubation was used.

PMID- 20805486
TI  - Oil sands development contributes elements toxic at low concentrations to the
      Athabasca River and its tributaries.
AB  - We show that the oil sands industry releases the 13 elements considered priority
      pollutants (PPE) under the US Environmental Protection Agency's Clean Water Act,
      via air and water, to the Athabasca River and its watershed. In the 2008
      snowpack, all PPE except selenium were greater near oil sands developments than
      at more remote sites. Bitumen upgraders and local oil sands development were
      sources of airborne emissions. Concentrations of mercury, nickel, and thallium in
      winter and all 13 PPE in summer were greater in tributaries with watersheds more
      disturbed by development than in less disturbed watersheds. In the Athabasca
      River during summer, concentrations of all PPE were greater near developed areas
      than upstream of development. At sites downstream of development and within the
      Athabasca Delta, concentrations of all PPE except beryllium and selenium remained
      greater than upstream of development. Concentrations of some PPE at one location
      in Lake Athabasca near Fort Chipewyan were also greater than concentration in the
      Athabasca River upstream of development. Canada's or Alberta's guidelines for the
      protection of aquatic life were exceeded for seven PPE-cadmium, copper, lead,
      mercury, nickel, silver, and zinc-in melted snow and/or water collected near or
      downstream of development.

PMID- 20805488
TI  - Prior knowledge of illumination for 3D perception in the human brain.
AB  - In perceiving 3D shape from ambiguous shading patterns, humans use the prior
      knowledge that the light is located above their head and slightly to the left.
      Although this observation has fascinated scientists and artists for a long time,
      the neural basis of this "light from above left" preference for the
      interpretation of 3D shape remains largely unexplored. Combining behavioral and
      functional MRI measurements coupled with multivoxel pattern analysis, we show
      that activations in early visual areas predict best the light source direction
      irrespective of the perceived shape, but activations in higher occipitotemporal
      and parietal areas predict better the perceived 3D shape irrespective of the
      light direction. These findings demonstrate that illumination is processed
      earlier than the representation of 3D shape in the visual system. In contrast to
      previous suggestions, we propose that prior knowledge about illumination is
      processed in a bottom-up manner and influences the interpretation of 3D structure
      at higher stages of processing.

PMID- 20805487
TI  - The serine/arginine-rich protein SF2/ASF regulates protein sumoylation.
AB  - Protein modification by conjugation of small ubiquitin-related modifier (SUMO) is
      involved in diverse biological functions, such as transcription regulation,
      subcellular partitioning, stress response, DNA damage repair, and chromatin
      remodeling. Here, we show that the serine/arginine-rich protein SF2/ASF, a factor
      involved in splicing regulation and other RNA metabolism-related processes, is a
      regulator of the sumoylation pathway. The overexpression of this protein
      stimulates, but its knockdown inhibits SUMO conjugation. SF2/ASF interacts with
      Ubc9 and enhances sumoylation of specific substrates, sharing characteristics
      with already described SUMO E3 ligases. In addition, SF2/ASF interacts with the
      SUMO E3 ligase PIAS1 (protein inhibitor of activated STAT-1), regulating PIAS1
      induced overall protein sumoylation. The RNA recognition motif 2 of SF2/ASF is
      necessary and sufficient for sumoylation enhancement. Moreover, SF2/ASF has a
      role in heat shock-induced sumoylation and promotes SUMO conjugation to RNA
      processing factors. These results add a component to the sumoylation pathway and
      a previously unexplored role for the multifunctional SR protein SF2/ASF.

PMID- 20805490
TI  - Multipotential hematopoietic blast colony-forming cells exhibit delays in self
      generation and lineage commitment.
AB  - Murine hematopoietic blast colony-forming cells (BL-CFCs) are able to generate up
      to 30,000 progeny blast cells within 10 d in agar cultures. Contained in these
      populations are large numbers of lineage-committed progenitor cells in the
      granulocytic and macrophage lineages. Sequential analyses of blast colonies
      revealed that self-generation of BL-CFCs occurs but is surprisingly late in
      clonal expansion, as is the emergence of progenitor cells committed to
      megakaryocytic and eosinophil lineages. Self-generating BL-CFCs were highly
      enriched in lineage(-) Kit(+) Sca1(+) CD34(-) Flt3R(-) populations, and colonies
      generated by such cells contained colony-forming units-spleen and formed
      erythroid and lymphoid progeny in vivo. The data suggest the existence of a
      hierarchical structure in BL-CFC populations with at least a subset being cells
      assayable as colony-forming units-spleen. Because BL-CFCs can self-generate and
      are able to generate lymphoid and myeloid populations, BL-CFCs appear to be ideal
      cells in which to analyze the processes of self-generation and lineage commitment
      in clonal in vitro cultures.

PMID- 20805489
TI  - D1 and D2 dopamine receptors in separate circuits cooperate to drive associative
      long-term potentiation in the prefrontal cortex.
AB  - Dopamine release associated with motivational arousal is thought to drive goal
      directed learning and consolidation of acquired memories. This dopamine
      hypothesis of learning and motivation directly suggests that dopamine is
      necessary for modifications of excitatory synapses in dopamine terminal fields,
      including the prefrontal cortex (PFC), to "stamp in" posttrial memory traces. It
      is unknown how such enabling occurs in native circuits tightly controlled by
      GABAergic inhibitory tone. Here we report that dopamine, via both D1-class
      receptors (D1Rs) and D2-class receptors (D2Rs), enables the induction of spike
      timing-dependent long-term potentiation (t-LTP) in layer V PFC pyramidal neurons
      over a "window" of more than 30 ms that is otherwise closed under intact
      inhibitory constraint. Dopamine acts at D2Rs in local GABAergic interneurons to
      suppress inhibitory transmission, gating the induction of t-LTP. Moreover,
      dopamine activates postsynaptic D1Rs in excitatory synapses to allow t-LTP
      induction at a substantially extended, normally ineffective, timing interval (+30
      ms), thus increasing the associability of prepost coincident stimuli. Although
      the D2R-mediated disinhibition alone is sufficient to gate t-LTP at a normal
      timing (+10 ms), t-LTP at +30 ms requires concurrent activation of both D1Rs and
      D2Rs. Our results illustrate a previously unrecognized circuit-level mechanism by
      which dopamine receptors in separate microcircuits cooperate to drive Hebbian
      synaptic plasticity across a significant temporal window under intact inhibition.
      This mechanism should be important in functioning of interconnected PFC
      microcircuits, in which D1Rs and D2Rs are not colocalized but their coactivation
      is necessary.

PMID- 20805491
TI  - Ancient pinnate leaf mimesis among lacewings.
AB  - Insects have evolved diverse methods of predator avoidance, many of which
      implicate complex adaptations of their wings (e.g., Phylliidae, Nymphalidae,
      Notodontidae). Among these, angiosperm leaf mimicry is one of the most dramatic,
      although the historical origins of such modifications are unclear owing to a
      dearth of paleontological records. Here, we report evidence of pinnate leaf
      mimesis in two lacewings (Neuroptera): Bellinympha filicifolia Y. Wang, Ren, Liu
      & Engel gen. et sp. nov. and Bellinympha dancei Y. Wang, Ren, Shih & Engel, sp.
      nov., from the Middle Jurassic, representing a 165-million-year-old
      specialization between insects and contemporaneous gymnosperms of the Cycadales
      or Bennettitales. Furthermore, such lacewings demonstrate a preangiosperm origin
      for leaf mimesis, revealing a lost evolutionary scenario of interactions between
      insects and gymnosperms. The current fossil record suggests that this enigmatic
      lineage became extinct during the Early Cretaceous, apparently closely correlated
      with the decline of Cycadales and Bennettitales at that time, and perhaps owing
      to the changing floral environment resulted from the rise of flowering plants.

PMID- 20805492
TI  - Comprehensive phylogeny of apid bees reveals the evolutionary origins and
      antiquity of cleptoparasitism.
AB  - Apidae is the most speciose and behaviorally diverse family of bees. It includes
      solitary, eusocial, socially parasitic, and an exceptionally high proportion of
      cleptoparasitic species. Cleptoparasitic bees, which are brood parasites in the
      nests of other bees, have long caused problems in resolving the phylogenetic
      relationships within Apidae based on morphological data because of the tendency
      for parasites to converge on a suite of traits, making it difficult to
      differentiate similarity caused by common ancestry from convergence. Here, we
      resolve the evolutionary history of apid cleptoparasitism by conducting a
      detailed, comprehensive molecular phylogenetic analysis of all 33 apid tribes
      (based on 190 species), including representatives from every hypothesized origin
      of cleptoparasitism. Based on Bayesian ancestral state reconstruction, we show
      that cleptoparasitism has arisen just four times in Apidae, which is fewer times
      than previously estimated. Our results indicate that 99% of cleptoparasitic apid
      bees form a monophyletic group. Divergence time estimates reveal that
      cleptoparasitism is an ancient behavior in bees that first evolved in the late
      Cretaceous 95 Mya [95% highest posterior density (HPD) = 87-103]. Our
      phylogenetic analysis of the Apidae sheds light on the macroevolution of a bee
      family that is of evolutionary, ecological, and economic importance.

PMID- 20805494
TI  - How to sample the carbon isotopes of tropical ecosystems without leaving your
      armchair.

PMID- 20805493
TI  - Preference of RIG-I for short viral RNA molecules in infected cells revealed by
      next-generation sequencing.
AB  - Intracellular detection of virus infections is a critical component of innate
      immunity carried out by molecules known as pathogen recognition receptors (PRRs).
      Activation of PRRs by their respective pathogen-associated molecular patterns
      (PAMPs) leads to production of proinflamatory cytokines, including type I IFN,
      and the establishment of an antiviral state in the host. Out of all PRRs found to
      date, retinoic acid inducible gene I (RIG-I) has been shown to play a key role in
      recognition of RNA viruses. On the basis of in vitro and transfection studies,
      5'ppp RNA produced during virus replication is thought to bind and activate this
      important sensor. However, the nature of RNA molecules that interact with
      endogenous RIG-I during the course of viral infection has not been determined. In
      this work we use next-generation RNA sequencing to show that RIG-I preferentially
      associates with shorter, 5'ppp containing viral RNA molecules in infected cells.
      We found that during Sendai infection RIG-I specifically bound the genome of the
      defective interfering (DI) particle and did not bind the full-length virus genome
      or any other viral RNAs. In influenza-infected cells RIG-I preferentially
      associated with shorter genomic segments as well as subgenomic DI particles. Our
      analysis for the first time identifies RIG-I PAMPs under natural infection
      conditions and implies that full-length genomes of single segmented RNA virus
      families are not bound by RIG-I during infection.

PMID- 20805495
TI  - Embryonic gonadotropin-releasing hormone signaling is necessary for maturation of
      the male reproductive axis.
AB  - Gonadotropin-releasing hormone (GnRH) signaling regulates reproductive physiology
      in mammals. GnRH is released by a subset of hypothalamic neurons and binds to
      GnRH receptor (GnRHR) on gonadotropes in the anterior pituitary gland to control
      production and secretion of gonadotropins that in turn regulate the activity of
      the gonads. Central control of reproduction is well understood in adult animals,
      but GnRH signaling has also been implicated in the development of the
      reproductive axis. To investigate the role of GnRH signaling during development,
      we selectively ablated GnRHR-expressing cells in mice. This genetic strategy
      permitted us to identify an essential stage in male reproductive axis
      development, which depends on embryonic GnRH signaling. Our experiments revealed
      a striking dichotomy in the gonadotrope population of the fetal anterior
      pituitary gland. We show that luteinizing hormone-expressing gonadotropes, but
      not follicle-stimulating hormone-expressing gonadotropes, express the GnRHR at
      embryonic day 16.75. Furthermore, we demonstrate that an embryonic increase in
      luteinizing hormone secretion is needed to promote development of follicle
      stimulating hormone-expressing gonadotropes, which might be mediated by paracrine
      interactions within the pituitary. Moreover, migration of GnRH neurons into the
      hypothalamus appeared normal with appropriate axonal connections to the median
      eminence, providing genetic evidence against autocrine regulation of GnRH
      neurons. Surprisingly, genetic ablation of GnRHR expressing cells significantly
      increased the number of GnRH neurons in the anterior hypothalamus, suggesting an
      unexpected role of GnRH signaling in establishing the size of the GnRH neuronal
      population. Our experiments define a functional role of embryonic GnRH signaling.

PMID- 20805496
TI  - Rapidly fatal myeloproliferative disorders in mice with deletion of Casitas B
      cell lymphoma (Cbl) and Cbl-b in hematopoietic stem cells.
AB  - Casitas B-cell lymphoma (Cbl)-family E3 ubiquitin ligases are negative regulators
      of tyrosine kinase signaling. Recent work has revealed a critical role of Cbl in
      the maintenance of hematopoietic stem cell (HSC) homeostasis, and mutations in
      CBL have been identified in myeloid malignancies. Here we show that, in contrast
      to Cbl or Cbl-b single-deficient mice, concurrent loss of Cbl and Cbl-b in the
      HSC compartment leads to an early-onset lethal myeloproliferative disease in
      mice. Cbl, Cbl-b double-deficient bone marrow cells are hypersensitive to
      cytokines, and show altered biochemical response to thrombopoietin. Thus, Cbl and
      Cbl-b play redundant but essential roles in HSC regulation, whose breakdown leads
      to hematological abnormalities that phenocopy crucial aspects of mutant Cbl
      driven human myeloid malignancies.

PMID- 20805497
TI  - Central serotonin neurons are required for arousal to CO2.
AB  - There is a long-standing controversy about the role of serotonin in sleep/wake
      control, with competing theories that it either promotes sleep or causes arousal.
      Here, we show that there is a marked increase in wakefulness when all serotonin
      neurons are genetically deleted in mice hemizygous for ePet1-Cre and homozygous
      for floxed Lmx1b (Lmx1b(f/f/p)). However, this only occurs at cool ambient
      temperatures and can be explained by a thermoregulatory defect that leads to an
      increase in motor activity to generate heat. Because some serotonin neurons are
      stimulated by CO(2), and serotonin activates thalamocortical networks, we
      hypothesized that serotonin neurons cause arousal in response to hypercapnia. We
      found that Lmx1b(f/f/p) mice completely lacked any arousal response to inhalation
      of 10% CO(2) (with 21% O(2) in balance N(2)) but had normal arousal responses to
      hypoxia, sound, and air puff. We propose that serotonin neurons mediate the
      potentially life-saving arousal response to hypercapnia. Impairment of this
      response may contribute to sudden unexpected death in epilepsy, sudden infant
      death syndrome, and sleep apnea.

PMID- 20805498
TI  - Cdc42 interacting protein 4 (CIP4) is essential for integrin-dependent T-cell
      trafficking.
AB  - The F-BAR domain containing protein CIP4 (Cdc42 interacting protein 4) interacts
      with Cdc42 and WASP/N-WASP and is thought to participate in the assembly of
      filamentous actin. CIP4(-/-) mice had normal T- and B-lymphocyte development but
      impaired T cell-dependent antibody production, IgG antibody affinity maturation,
      and germinal center (GC) formation, despite an intact CD40L-CD40 axis. CIP4(-/-)
      mice also had impaired contact hypersensitivity (CHS) to haptens, and their T
      cells failed to adoptively transfer CHS. Ovalbumin-activated CD4(+) effector T
      cells from CIP4(-/-)/OT-II mice migrated poorly to antigen-challenged skin.
      Activated CIP4(-/-) T cells exhibited impaired adhesion and polarization on
      immobilized VCAM-1 and ICAM-1 and defective arrest and transmigration across
      murine endothelial cell monolayers under shear flow conditions. These results
      demonstrate an important role for CIP4 in integrin-dependent T cell-dependent
      antibody responses and GC formation and in integrin-mediated recruitment of
      effector T cells to cutaneous sites of antigen-driven immune reactions.

PMID- 20805500
TI  - Ubiquitination of lysine-331 by Kaposi's sarcoma-associated herpesvirus protein
      K5 targets HFE for lysosomal degradation.
AB  - The nonclassical MHC class I-related (MHC-I) molecule HFE controls cellular iron
      homeostasis by a mechanism that has not been fully elucidated. We examined the
      regulation of HFE by K5, the E3 ubiquitin ligase encoded by Kaposi's sarcoma
      associated herpesvirus (KSHV/HHV8), that is known to down-regulate classical MHC
      I. K5 down-regulated HFE efficiently, using polyubiquitination of the membrane
      proximal lysine in the HFE cytoplasmic tail (K331), to target the molecule for
      degradation via ESCRT1/TSG101-dependent sorting from endosomes to multivesicular
      bodies (MVBs)/lysosomes. In the primary effusion lymphoma cell line BC-3, which
      carries latent KSHV, HFE was degraded rapidly upon virus reactivation. HFE was
      ubiquitinated on lysine-331 in unactivated BC-3 cells, conditions where K5 was
      not detectable, consistent with an endogenous E3 ubiquitin ligase controlling HFE
      expression. The results show regulated expression of HFE by ubiquitination,
      consistent with a role in cellular iron homeostasis, a molecular mechanism
      targeted by KSHV to achieve a positive iron balance.

PMID- 20805499
TI  - Endosomal-sorting complexes required for transport (ESCRT) pathway-dependent
      endosomal traffic regulates the localization of active Src at focal adhesions.
AB  - Active Src localization at focal adhesions (FAs) is essential for cell migration.
      How this pool is linked mechanistically to the large pool of Src at late
      endosomes (LEs)/lysosomes (LY) is not well understood. Here, we used inducible
      Tsg101 gene deletion, TSG101 knockdown, and dominant-negative VPS4 expression to
      demonstrate that the localization of activated cellular Src and viral Src at FAs
      requires the endosomal-sorting complexes required for transport (ESCRT) pathway.
      Tsg101 deletion also led to impaired Src-dependent activation of STAT3 and focal
      adhesion kinase and reduced cell migration. Impairment of the ESCRT pathway or
      Rab7 function led to the accumulation of active Src at aberrant LE/LY
      compartments followed by its loss. Analyses using fluorescence recovery after
      photo-bleaching show that dynamic mobility of Src in endosomes is ESCRT pathway
      dependent. These results reveal a critical role for an ESCRT pathway-dependent
      LE/LY trafficking step in Src function by promoting localization of active Src to
      FAs.

PMID- 20805501
TI  - Focal Mullerian duct retention in male mice with constitutively activated beta
      catenin expression in the Mullerian duct mesenchyme.
AB  - Mullerian-inhibiting substance (MIS), which is produced by fetal Sertoli cells
      shortly after commitment of the bipotential gonads to testicular differentiation,
      causes Mullerian duct (MD) regression. In the fetal female gonads, MIS is not
      expressed and the MDs will differentiate into the internal female reproductive
      tract. We have investigated whether dysregulated beta-catenin activity affects MD
      regression by expressing a constitutively activated nuclear form of beta-catenin
      in the MD mesenchyme. We show that constitutively activated (CA) beta-catenin
      causes focal retention of MD tissue in the epididymides and vasa deferentia. In
      adult mutant mice, the retained MD tissues express alpha-smooth muscle actin and
      desmin, which are markers for uterine differentiation. MD retention inhibited the
      folding complexity of the developing epididymides and usually led to obstructive
      azoospermia by spermatoceles. The MDs of urogenital ridges from mutant female
      embryos showed less regression with added MIS in organ culture compared with
      control MDs when analyzed by whole mount in situ hybridization for Wnt7a as a
      marker for the MD epithelium. CA beta-catenin did not appear to affect expression
      of either MIS in the embryonic testes or its type II receptor (AMHR2) in the MD
      mesenchyme nor did it inhibit pSmad1/5/8 nuclear accumulation, suggesting that
      dysregulated beta-catenin must inhibit MD regression independently of MIS
      signaling. These studies suggest that dysregulated Wnt/beta-catenin signaling in
      the MD mesenchyme might also be a contributing factor in persistent Mullerian
      duct syndrome, a form of male pseudohermaphroditism, and development of
      spermatoceles.

PMID- 20805502
TI  - Imaging mass spectrometry of intraspecies metabolic exchange revealed the
      cannibalistic factors of Bacillus subtilis.
AB  - During bacterial cannibalism, a differentiated subpopulation harvests nutrients
      from their genetically identical siblings to allow continued growth in nutrient
      limited conditions. Hypothesis-driven imaging mass spectrometry (IMS) was used to
      identify metabolites active in a Bacillus subtilis cannibalism system in which
      sporulating cells lyse nonsporulating siblings. Two candidate molecules with
      sequences matching the products of skfA and sdpC, genes for the proposed
      cannibalistic factors sporulation killing factor (SKF) and sporulation delaying
      protein (SDP), respectively, were identified and the structures of the final
      products elucidated. SKF is a cyclic 26-amino acid (aa) peptide that is
      posttranslationally modified with one disulfide and one cysteine thioether
      bridged to the alpha-position of a methionine, a posttranslational modification
      not previously described in biology. SDP is a 42-residue peptide with one
      disulfide bridge. In spot test assays on solid medium, overproduced SKF and SDP
      enact a cannibalistic killing effect with SDP having higher potency. However,
      only purified SDP affected B. subtilis cells in liquid media in fluorescence
      microscopy and growth assays. Specifically, SDP treatment delayed growth in a
      concentration-dependent manner, caused increases in cell permeability, and
      ultimately caused cell lysis accompanied by the production of membrane tubules
      and spheres. Similarly, SDP but not SKF was able to inhibit the growth of the
      pathogens Staphylococcus aureus and Staphylococcus epidermidis with comparable
      IC(50) to vancomycin. This investigation, with the identification of SKF and SDP
      structures, highlights the strength of IMS in investigations of metabolic
      exchange of microbial colonies and also demonstrates IMS as a promising approach
      to discover novel biologically active molecules.

PMID- 20805503
TI  - Genome mining and genetic analysis of cypemycin biosynthesis reveal an unusual
      class of posttranslationally modified peptides.
AB  - Posttranslational modification of amino acids confers a range of structural
      features and activities on ribosomally synthesized peptides, many of which have
      potent antimicrobial or other biological activities. Cypemycin is an extensively
      modified linear peptide produced by Streptomyces sp. OH-4156 with potent in vitro
      activity against mouse leukemia cells. Cypemycin does not contain lanthionine
      bridges but exhibits some of the structural features of lantibiotics, notably
      dehydrated threonines (dehydrobutyrines) and a C-terminal S-[(Z)-2-aminovinyl]-D
      cysteine. Consequently it was classified as a member of the lantibiotic family of
      posttranslationally modified peptides. Cypemycin also possesses two L-allo
      isoleucine residues and an N-terminal N,N-dimethylalanine, both unique amino acid
      modifications. We identified and heterologously expressed the cypemycin
      biosynthetic gene cluster and performed a mutational analysis of each individual
      gene. We show that even the previously described modifications are carried out by
      unusual enzymes or via a modification pathway unrelated to lantibiotic
      biosynthesis. Bioinformatic analysis revealed the widespread occurrence of
      cypemycin-like gene clusters within the bacterial kingdom and in the Archaea.
      Cypemycin is the founding member of an unusual class of posttranslationally
      modified ribosomally synthesized peptides, the linaridins.

PMID- 20805504
TI  - Wnt/beta-catenin signaling is involved in the induction and maintenance of
      primitive hematopoiesis in the vertebrate embryo.
AB  - The formation of primitive (embryonic) blood in vertebrates is mediated by spatio
      temporally restricted signaling between different tissue layers. In Xenopus, in
      which primitive blood originates in the ventral blood island, this involves the
      secretion of bone morphogenetic protein (BMP) ligands by the ectoderm that signal
      to the underlying mesoderm during gastrulation. Using novel transgenic reporter
      lines, we report that the canonical Wnt/beta-catenin pathway is also activated in
      the blood islands in Xenopus. Furthermore, Wnt-reporter activity was also
      detected in the blood islands of the mouse yolk sac. By using morpholino-mediated
      depletion in Xenopus, we identified Wnt4 as the ligand that is expressed in the
      mesoderm of the ventral blood island and is essential for the expression of
      hematopoietic and erythroid marker genes. Injection of an inducible Wnt
      interfering construct further showed that, during gastrulation, Wnt/beta-catenin
      signaling is required both in the mesoderm and in the overlying ectoderm for the
      formation of the ventral blood island. Using recombination assays with embryonic
      explants, we document that ectodermal BMP4 expression is dependent on Wnt4
      signals from the mesoderm. Our results thus reveal a unique role for Wnt4
      mediated canonical signaling in the formation and maintenance of the ventral
      blood island in Xenopus.

PMID- 20805505
TI  - Proline-rich tyrosine kinase-2 is critical for CD8 T-cell short-lived effector
      fate.
AB  - T-cell interactions with antigen-presenting cells are important for CD8 T-cell
      effector or memory fate determination. The integrin leukocyte function-associated
      antigen-1 (LFA-1) mediates T-cell adhesion but the contribution of LFA-1-induced
      signaling pathways to T-cell responses is poorly understood. Here we demonstrate
      that proline-rich tyrosine kinase-2 (PYK2) deficiency impairs CD8 T-cell
      activation by synergistic LFA-1 and T-cell receptor stimulation. Furthermore,
      PYK2 is essential for LFA-1-mediated CD8 T-cell adhesion and LFA-1 costimulation
      of CD8 T-cell migration. During lymphocytic choriomeningitis virus infection in
      vivo, PYK2 deficiency results in a specific loss of short-lived effector CD8 T
      cells but does not affect memory-precursor CD8 T-cell development. Similarly,
      lack of LFA-1 primarily impairs the generation of short-lived effector cells.
      Thus, PYK2 facilitates LFA-1-dependent CD8 T-cell responses and promotes CD8 T
      cell short-lived effector fate, suggesting that PYK2 may be an interesting
      therapeutic target to suppress exacerbated CD8 T-cell responses.

PMID- 20805507
TI  - Alterations in choice behavior by manipulations of world model.
AB  - How to compute initially unknown reward values makes up one of the key problems
      in reinforcement learning theory, with two basic approaches being used. Model
      free algorithms rely on the accumulation of substantial amounts of experience to
      compute the value of actions, whereas in model-based learning, the agent seeks to
      learn the generative process for outcomes from which the value of actions can be
      predicted. Here we show that (i) "probability matching"-a consistent example of
      suboptimal choice behavior seen in humans-occurs in an optimal Bayesian model
      based learner using a max decision rule that is initialized with ecologically
      plausible, but incorrect beliefs about the generative process for outcomes and
      (ii) human behavior can be strongly and predictably altered by the presence of
      cues suggestive of various generative processes, despite statistically identical
      outcome generation. These results suggest human decision making is rational and
      model based and not consistent with model-free learning.

PMID- 20805506
TI  - Identification of differential and functionally active miRNAs in both anaplastic
      lymphoma kinase (ALK)+ and ALK- anaplastic large-cell lymphoma.
AB  - Aberrant anaplastic lymphoma kinase (ALK) expression is a defining feature of
      many human cancers and was identified first in anaplastic large-cell lymphoma
      (ALCL), an aggressive non-Hodgkin T-cell lymphoma. Since that time, many studies
      have set out to identify the mechanisms used by aberrant ALK toward
      tumorigenesis. We have identified a distinct profile of micro-RNAs (miRNAs) that
      characterize ALCL; furthermore, this profile distinguishes ALK(+) from ALK(-)
      subtypes, and thus points toward potential mechanisms of tumorigenesis induced by
      aberrant ALK. Using a nucleophosmin-ALK transgenic mouse model as well as human
      primary ALCL tumor tissues and human ALCL-derived cell lines, we reveal a set of
      overlapping deregulated miRNAs that might be implicated in the development and
      progression of ALCL. Importantly, ALK(+) and ALK(-) ALCL could be distinguished
      by a distinct profile of "oncomirs": Five members of the miR-17-92 cluster were
      expressed more highly in ALK(+) ALCL, whereas miR-155 was expressed more than 10
      fold higher in ALK(-) ALCL. Moreover, miR-101 was down-regulated in all ALCL
      model systems, but its forced expression attenuated cell proliferation only in
      ALK(+) and not in ALK(-) cell lines, perhaps suggesting different modes of ALK
      dependent regulation of its target proteins. Furthermore, inhibition of mTOR,
      which is targeted by miR-101, led to reduced tumor growth in engrafted ALCL mouse
      models. In addition to future therapeutical and diagnostic applications, it will
      be of interest to study the physiological implications and prognostic value of
      the identified miRNA profiles.

PMID- 20805508
TI  - Mechanism of Trypanosoma brucei gambiense (group 1) resistance to human
      trypanosome lytic factor.
AB  - Human innate immunity against most African trypanosomes, including Trypanosoma
      brucei brucei, is mediated by a minor subclass of toxic serum HDL, called
      trypanosome lytic factor-1 (TLF-1). This HDL contains two primate specific
      proteins, apolipoprotein L-1 and haptoglobin (Hp)-related protein, as well as
      apolipoprotein A-1. These assembled proteins provide a powerful defense against
      trypanosome infection. Trypanosoma brucei rhodesiense causes human African
      sleeping sickness because it has evolved an inhibitor of TLF-1, serum resistance
      associated (SRA) protein. Trypanosoma brucei gambiense lacks the SRA gene, yet it
      infects humans. As transfection of T. b. gambiense (group 1) is not possible, we
      initially used in vitro-selected TLF-1-resistant T. b. brucei to examine SRA
      independent mechanisms of TLF-1 resistance. Here we show that TLF-1 resistance in
      T. b. brucei is caused by reduced expression of the Hp/Hb receptor gene
      (TbbHpHbR). Importantly, T. b. gambiense (group 1) also showed a marked reduction
      in uptake of TLF-1 and a corresponding decrease in expression of T. b. gambiense
      Hp/Hb receptor (TbgHpHbR). Ectopic expression of TbbHpHbR in TLF-1-resistant T.
      b. brucei rescued TLF-1 uptake, demonstrating that decreased TbbHpHbR expression
      conferred TLF-1 resistance. Ectopic expression of TbgHpHbR in TLF-1-resistant T.
      b. brucei failed to rescue TLF-1 killing, suggesting that coding sequence changes
      altered Hp/Hb receptor binding affinity for TLF-1. We propose that the
      combination of coding sequence mutations and decreased expression of TbgHpHbR
      directly contribute to parasite evasion of human innate immunity and infectivity
      of group 1 T. b. gambiense.

PMID- 20805510
TI  - Early evidence (ca. 12,000 B.P.) for feasting at a burial cave in Israel.
AB  - Feasting is one of humanity's most universal and unique social behaviors.
      Although evidence for feasting is common in the early agricultural societies of
      the Neolithic, evidence in pre-Neolithic contexts is more elusive. We found clear
      evidence for feasting on wild cattle and tortoises at Hilazon Tachtit cave, a
      Late Epipaleolithic (12,000 calibrated years B.P.) burial site in Israel. This
      includes unusually high densities of butchered tortoise and wild cattle remains
      in two structures, the unique location of the feasting activity in a burial cave,
      and the manufacture of two structures for burial and related feasting activities.
      The results indicate that community members coalesced at Hilazon to engage in
      special rituals to commemorate the burial of the dead and that feasts were
      central elements in these important events. Feasts likely served important roles
      in the negotiation and solidification of social relationships, the integration of
      communities, and the mitigation of scalar stress. These and other social changes
      in the Natufian period mark significant changes in human social complexity that
      continued into the Neolithic period. Together, social and economic change signal
      the very beginning of the agricultural transition.

PMID- 20805509
TI  - CCAAT/enhancer binding protein delta (C/EBPdelta, CEBPD)-mediated nuclear import
      of FANCD2 by IPO4 augments cellular response to DNA damage.
AB  - Maintenance of genomic integrity is an essential cellular function. We previously
      reported that the transcription factor and tumor suppressor CCAAT/enhancer
      binding protein delta (C/EBPdelta, CEBPD; also known as "NFIL-6beta") promotes
      genomic stability. However, the molecular mechanism was not known. Here, we show
      that C/EBPdelta is a DNA damage-induced gene, which supports survival of mouse
      bone marrow cells, mouse embryo fibroblasts (MEF), human fibroblasts, and breast
      tumor cells in response to the DNA cross-linking agent mitomycin C (MMC). Using
      gene knockout, protein depletion, and overexpression studies, we found that
      C/EBPdelta promotes monoubiquitination of the Fanconi anemia complementation
      group D2 protein (FANCD2), which is necessary for its function in replication
      associated DNA repair. C/EBPdelta interacts with FANCD2 and importin 4 (IPO4,
      also known as "Imp4" and "RanBP4") via separate domains, mediating FANCD2-IPO4
      association and augmenting nuclear import of FANCD2, a prerequisite for its
      monoubiquitination. This study identifies a transcription-independent activity of
      C/EBPdelta in the DNA damage response that may in part underlie its tumor
      suppressor function. Furthermore, we report a function of IPO4 and nuclear import
      in the Fanconi anemia pathway of DNA repair.

PMID- 20805511
TI  - No evidence of nanodiamonds in Younger-Dryas sediments to support an impact
      event.
AB  - The causes of the late Pleistocene megafaunal extinctions in North America,
      disappearance of Clovis paleoindian lithic technology, and abrupt Younger-Dryas
      (YD) climate reversal of the last deglacial warming in the Northern Hemisphere
      remain an enigma. A controversial hypothesis proposes that one or more cometary
      airbursts/impacts barraged North America ~12,900 cal yr B.P. and caused these
      events. Most evidence supporting this hypothesis has been discredited except for
      reports of nanodiamonds (including the rare hexagonal polytype) in Bolling
      Allerod-YD-boundary sediments. The hexagonal polytype of diamond, lonsdaleite, is
      of particular interest because it is often associated with shock pressures
      related to impacts where it has been found to occur naturally. Unfortunately,
      previous reports of YD-boundary nanodiamonds have left many unanswered questions
      regarding the nature and occurrence of the nanodiamonds. Therefore, we examined
      carbon-rich materials isolated from sediments dated 15,818 cal yr B.P. to present
      (including the Bolling-Allerod-YD boundary). No nanodiamonds were found in our
      study. Instead, graphene- and graphene/graphane-oxide aggregates are ubiquitous
      in all specimens examined. We demonstrate that previous studies misidentified
      graphene/graphane-oxide aggregates as hexagonal diamond and likely misidentified
      graphene as cubic diamond. Our results cast doubt upon one of the last widely
      discussed pieces of evidence supporting the YD impact hypothesis.

PMID- 20805512
TI  - The liquid-liquid phase transition in silicon revealed by snapshots of valence
      electrons.
AB  - The basis for the anomalies of water is still mysterious. Quite generally
      tetrahedrally coordinated systems, also silicon, show similar thermodynamic
      behavior but lack--like water--a thorough explanation. Proposed models-
      controversially discussed--explain the anomalies as a remainder of a first-order
      phase transition between high and low density liquid phases, buried deeply in the
      "no man's land"--a part of the supercooled liquid region where rapid
      crystallization prohibits any experimental access. Other explanations doubt the
      existence of the phase transition and its first-order nature. Here, we provide
      experimental evidence for the first-order-phase transition in silicon. With
      ultrashort optical pulses of femtosecond duration we instantaneously heat the
      electronic system of silicon while the atomic structure as defined by the much
      heavier nuclear system remains initially unchanged. Only on a picosecond time
      scale the energy is transferred into the atomic lattice providing the energy to
      drive the phase transitions. With femtosecond X-ray pulses from FLASH, the free
      electron laser at Hamburg, we follow the evolution of the valence electronic
      structure during this process. As the relevant phases are easily distinguishable
      in their electronic structure, we track how silicon melts into the low-density
      liquid phase while a second phase transition into the high-density-liquid phase
      only occurs after the latent heat for the first-order phase transition has been
      transferred to the atomic structure. Proving the existence of the liquid-liquid
      phase transition in silicon, the hypothesized liquid-liquid scenario for water is
      strongly supported.

PMID- 20805513
TI  - Nonuniversal power law scaling in the probability distribution of scientific
      citations.
AB  - We develop a model for the distribution of scientific citations. The model
      involves a dual mechanism: in the direct mechanism, the author of a new paper
      finds an old paper A and cites it. In the indirect mechanism, the author of a new
      paper finds an old paper A only via the reference list of a newer intermediary
      paper B, which has previously cited A. By comparison to citation databases, we
      find that papers having few citations are cited mainly by the direct mechanism.
      Papers already having many citations ("classics") are cited mainly by the
      indirect mechanism. The indirect mechanism gives a power-law tail. The "tipping
      point" at which a paper becomes a classic is about 25 citations for papers
      published in the Institute for Scientific Information (ISI) Web of Science
      database in 1981, 31 for Physical Review D papers published from 1975-1994, and
      37 for all publications from a list of high h-index chemists assembled in 2007.
      The power-law exponent is not universal. Individuals who are highly cited have a
      systematically smaller exponent than individuals who are less cited.

PMID- 20805514
TI  - An aberrant island-dwelling theropod dinosaur from the Late Cretaceous of
      Romania.
AB  - Islands are noted for the occurrence of aberrant, endemic, and dwarfed taxa (the
      "island effect"). Late Cretaceous vertebrate assemblages of Romania and elsewhere
      in Europe are classic examples of island faunas in the fossil record, and are
      characterized by dwarfed herbivorous dinosaurs and other endemic taxa that are
      noticeably primitive relative to their mainland contemporaries. Fossils of the
      predators inhabiting the European paleoislands, however, are exceptionally rare
      and fragmentary. We describe a new dromaeosaurid theropod, based on an
      articulated skeleton from the Maastrichtian of Romania, which represents the most
      complete predatory dinosaur from the middle to Late Cretaceous of Europe. This
      taxon is characterized by a peculiar body plan, most notably extensive fusion in
      the hand and distal hindlimb, a highly retroverted pelvis with enlarged femoral
      muscle attachments, and a pair of hyperextensive pedal claws. However, unlike the
      island-dwelling herbivorous dinosaurs, its closest relatives are contemporary
      similar-sized Laurasian taxa, indicating faunal connections between Asia and the
      European islands late into the Cretaceous. This theropod provides support for the
      aberrant nature of the Late Cretaceous European island-dwelling dinosaurs, but
      indicates that predators on these islands were not necessarily small,
      geographically endemic, or primitive.

PMID- 20805516
TI  - Quantifying forest change.

PMID- 20805515
TI  - Catalytic and chaperone-like functions in an intrinsically disordered protein
      associated with desiccation tolerance.
AB  - Intrinsically disordered proteins (IDPs) lack well-defined structure but are
      widely represented in eukaryotic proteomes. Although the functions of most IDPs
      are not understood, some have been shown to have molecular recognition and/or
      regulatory roles where their disordered nature might be advantageous. Anhydrin is
      an uncharacterized IDP induced by dehydration in an anhydrobiotic nematode,
      Aphelenchus avenae. We show here that anhydrin is a moonlighting protein with two
      novel, independent functions relating to desiccation tolerance. First, it has a
      chaperone-like activity that can reduce desiccation-induced enzyme aggregation
      and inactivation in vitro. When expressed in a human cell line, anhydrin
      localizes to the nucleus and reduces the propensity of a polyalanine expansion
      protein associated with oculopharyngeal muscular dystrophy to form aggregates.
      This in vivo activity is distinguished by a loose association of anhydrin with
      its client protein, consistent with a role as a molecular shield. In addition,
      anhydrin exhibits a second function as an endonuclease whose substrates include
      supercoiled, linear, and chromatin linker DNA. This nuclease activity could be
      involved in either repair of desiccation-induced DNA damage incurred during
      anhydrobiosis or in apoptotic or necrotic processes, for example, but it is
      particularly unexpected for anhydrin because IDP functions defined to date
      anticorrelate with enzyme activity. Enzymes usually require precise three
      dimensional positioning of residues at the active site, but our results suggest
      this need not be the case. Anhydrin therefore extends the range of IDP functional
      categories to include catalysis and highlights the potential for the discovery of
      new functions in disordered proteomes.

PMID- 20805518
TI  - Teaching neuroimages: Villaret syndrome.

PMID- 20805520
TI  - Nonconvulsive status epilepticus and brain damage: further evidence, more
      questions.

PMID- 20805521
TI  - The four seasons of multiple sclerosis.

PMID- 20805522
TI  - MRS in presymptomatic MAPT mutation carriers: a potential biomarker for tau
      mediated pathology.
AB  - OBJECTIVE: To determine the proton magnetic resonance spectroscopy ((1)H MRS)
      changes in carriers of microtubule-associated protein (MAPT) mutations in a case
      control study. METHODS: Patients with MAPT mutations (N279K, V337M, R406W, IVS9
      10G>T, P301L) from 5 different families (n = 24) underwent MRI and single voxel
      (1)H MRS from the posterior cingulate gyrus inferior precuneus at 3 T. Ten of the
      patients were symptomatic with median Clinical Dementia Rating sum of boxes score
      (CDR-SOB) of 6.5 and 14 patients were presymptomatic with CDR-SOB of 0. Age- and
      sex-matched controls (n = 24) were recruited. RESULTS: Symptomatic MAPT mutation
      carriers were characterized by decreased N-acetylaspartate/creatine (NAA/Cr)
      ratio, an index of neuronal integrity, increased myoinositol (mI)/Cr ratio, a
      possible marker for glial activity, decreased NAA/mI, and hippocampal atrophy (p
      < 0.001). Whereas presymptomatic MAPT mutation carriers had elevated mI/Cr and
      decreased NAA/mI (p < 0.001), NAA/Cr levels and hippocampal volumes were not
      different from controls. Decrease in NAA/Cr (R(2) = 0. 22; p = 0.021) and
      hippocampal volumes (R(2) = 0.46; p < 0.001) were associated with proximity to
      the expected or actual age at symptom onset in MAPT mutation carriers.
      CONCLUSION: (1)H MRS metabolite abnormalities characterized by an elevated mI/Cr
      and decreased NAA/mI are present several years before the onset of symptoms in
      MAPT mutation carriers. The data suggest an ordered sequencing of the (1)H MRS
      and MRI biomarkers. MI/Cr, a possible index of glial proliferation, precedes the
      decrease in neuronal integrity marker NAA/Cr and hippocampal atrophy. (1)H MRS
      may be a useful inclusion biomarker for preventive trials in presymptomatic
      carriers of MAPT mutations and possibly other proteinopathies.

PMID- 20805523
TI  - Secular changes in cognitive predictors of dementia and mortality in 70-year
      olds.
AB  - BACKGROUND: Successive elderly birth cohorts improved in cognitive performance
      during the 20th century. It is not clear whether this influences cognitive
      predictors of dementia and mortality. OBJECTIVE: In 2 longitudinal population
      studies, representing 2 cohorts of 70-year-olds examined 30 years apart, we
      investigated the relation between baseline cognitive function and 5-year
      occurrence of dementia and mortality. METHODS: Two representative cohorts of 70
      year-olds initially free from dementia born in 1901-1902 (cohort 1901-1902: n =
      381) and 1930 (cohort 1930: n = 551) from Gothenburg, Sweden, were examined in
      1971-1972 and 2000-2001 and after 5 years for the outcome of dementia and death.
      Recent memory was evaluated during psychiatric examinations, and nonmemory
      domains using psychometric tests. RESULTS: At age 70, cohort 1930 performed
      better on psychometric tests, and had fewer recent memory problems compared to
      cohort 1901-1902. During 5-year follow-up, 5.0% in cohort 1901-1902 and 4.4% in
      cohort 1930 (p = 0.742) developed dementia, and 15.7% in cohort 1901-1902 and
      4.4% in cohort 1930 died (p < 0.001). Recent memory was associated with incident
      dementia in both cohorts. Low scores in nonmemory tests were associated with
      incident dementia in cohort 1901-1902, but not in cohort 1930. Recent memory
      problems and lower scores in nonmemory tests were associated with 5-year
      mortality in cohort 1901-1902, but not in cohort 1930. CONCLUSIONS: Secular
      changes in cognitive performance may influence cognitive predictors of dementia
      and mortality, despite similar incidence of dementia. The findings should be
      taken cautiously due to differences between cohorts in refusal rates, quality of
      education, and dementia recognition in medical records.

PMID- 20805524
TI  - Change in risk of Alzheimer disease over time.
AB  - OBJECTIVE: To assess whether the risk of incidence of Alzheimer disease (AD)
      varies over time. The increase in numbers of people at the oldest ages in the
      population will bring an increase in the number of people with AD. Projections of
      the size of the increase assume the risk of AD is constant. METHODS: All persons
      age 65 or older in a biracial, geographically defined area were invited to
      participate in a home interview every 3 years. From the approximately 10,000
      participants, stratified random samples were selected for detailed clinical
      evaluation. At each cycle, individuals determined free of AD in a previous cycle,
      either by examination or by high score on cognitive function tests, were sampled
      in the subsequent cycle for evaluation for incident AD. The evaluations for
      disease were structured and uniform across time. These analyses include 1,695
      subjects evaluated for incident disease from 1997 through 2008. RESULTS: AD
      developed in 360 participants. Change over time in risk of incident disease was
      assessed in logistic regression analyses including evaluation date and
      controlling for age, gender, education, race, interval from disease-free
      designation to evaluation for incident disease, and sample design. The time
      variable (in years) was not significant (odds ratio = 0.970, 95% confidence
      interval = 0.902 to 1.044). CONCLUSIONS: The null relation of evaluation date to
      disease incidence suggests no recent change in risk of AD over time, and supports
      this assumption for projections of AD.

PMID- 20805525
TI  - Nonconvulsive seizures after traumatic brain injury are associated with
      hippocampal atrophy.
AB  - OBJECTIVE: To determine if posttraumatic nonconvulsive electrographic seizures
      result in long-term brain atrophy. METHODS: Prospective continuous EEG (cEEG)
      monitoring was done in 140 patients with moderate to severe traumatic brain
      injury (TBI) and in-depth study of 16 selected patients was done using serial
      volumetric MRI acutely and at 6 months after TBI. Fluorodeoxyglucose PET was done
      in the acute stage in 14/16 patients. These data were retrospectively analyzed
      after collection of data for 7 years. RESULTS: cEEG detected seizures in 32/140
      (23%) of the entire cohort. In the selected imaging subgroup, 6 patients with
      seizures were compared with a cohort of 10 age- and GCS-matched patients with TBI
      without seizures. In this subgroup, the seizures were repetitive and constituted
      status epilepticus in 4/6 patients. Patients with seizures had greater
      hippocampal atrophy as compared to those without seizures (21 +/- 9 vs 12 +/- 6%,
      p = 0.017). Hippocampi ipsilateral to the electrographic seizure focus
      demonstrated a greater degree of volumetric atrophy as compared with nonseizure
      hippocampi (28 +/- 5 vs 13 +/- 9%, p = 0.007). A single patient had an ictal PET
      scan which demonstrated increased hippocampal glucose uptake. CONCLUSION: Acute
      posttraumatic nonconvulsive seizures occur frequently after TBI and, in a
      selected subgroup, appear to be associated with disproportionate long-term
      hippocampal atrophy. These data suggest anatomic damage is potentially elicited
      by nonconvulsive seizures in the acute postinjury setting.

PMID- 20805526
TI  - Seasonal prevalence of MS disease activity.
AB  - OBJECTIVE: This observational cohort study investigated the seasonal prevalence
      of multiple sclerosis (MS) disease activity (likelihood and intensity), as
      reflected by new lesions from serial T2-weighted MRI, a sensitive marker of
      subclinical disease activity. METHODS: Disease activity was assessed from the
      appearance of new T2 lesions on 939 separate brain MRI examinations in 44
      untreated patients with MS. Likelihood functions for MS disease activity were
      derived, accounting for the temporal uncertainty of new lesion occurrence,
      individual levels of disease activity, and uneven examination intervals. Both
      likelihood and intensity of disease activity were compared with the time of year
      (season) and regional climate data (temperature, solar radiation, precipitation)
      and among relapsing and progressive disease phenotypes. Contrast-enhancing
      lesions and attack counts were also compared for seasonal effects. RESULTS:
      Unlike contrast enhancement or attacks, new T2 activity revealed a likelihood 2-3
      times higher in March-August than during the rest of the year, and correlated
      strongly with regional climate data, in particular solar radiation. In addition
      to the likelihood or prevalence, disease intensity was also elevated during the
      summer season. The elevated risk season appears to lessen for progressive MS and
      occur about 2 months earlier. CONCLUSION: This study documents evidence of a
      strong seasonal pattern in subclinical MS activity based on noncontrast brain
      MRI. The observed seasonality in MS disease activity has implications for trial
      design and therapy assessment. The observed activity pattern is suggestive of a
      modulating role of seasonally changing environmental factors or season-dependent
      metabolic activity.

PMID- 20805527
TI  - Correlates of outcome and response to IVIg in 88 patients with multifocal motor
      neuropathy.
AB  - OBJECTIVE: Identification and examination of all patients with multifocal motor
      neuropathy (MMN) in the Netherlands to document the clinical spectrum and
      response to IV immunoglobulin (IVIg) and to determine correlates of outcome.
      METHODS: A national cross-sectional descriptive study was performed. Ninety-seven
      patients were identified; 88 participated. Logistic regression analysis was used
      to study determinants of outcome. RESULTS: Age at onset was younger in men than
      in women (38 vs 45 years, p = 0.05). Onset of weakness was in distal arm (61%) or
      distal leg (34%), and occasionally in the upper arm (5%). Initial diagnosis was
      motor neuron disease in one-third of patients. Brisk, but not pathologic,
      reflexes in weakened muscles were found in 8%. Conduction blocks were most
      frequently detected in the ulnar (80%) and median (77%) nerves, but occasionally
      only between Erb and axilla (6%), or in the musculocutaneous nerve (1%). Ninety
      four percent responded to IVIg therapy: nonresponders had longer disease duration
      before the first treatment (p = 0.03). Seventy-six percent received IVIg
      maintenance treatment at the time of this study (median duration 6 years; range 0
      17): the median dose increased over the years from 12 to 17 g per week (p <
      0.01). Independent determinants of more severe weakness and disability were axon
      loss (p < 0.001; p < 0.0001) and longer disease duration without IVIg (p = 0.03;
      p = 0.07). CONCLUSION: The results of this study may help aid recognition the
      clinical picture of MMN. Early IVIg treatment may help to postpone axonal
      degeneration and permanent deficits. CLASSIFICATION OF EVIDENCE: This study
      provides Class IV evidence that IVIg improves muscle strength of patients with
      MMN and disability (defined as an increase of >or=1 Medical Research Council
      grade in at least 2 muscle groups without decrease in other muscle groups) in 94%
      (95% confidence interval, 86.8%-97.4%) of patients.

PMID- 20805528
TI  - Docosahexaenoic acid therapy in peroxisomal diseases: results of a double-blind,
      randomized trial.
AB  - OBJECTIVES: Peroxisome assembly disorders are genetic disorders characterized by
      biochemical abnormalities, including low docosahexaenoic acid (DHA). The
      objective was to assess whether treatment with DHA supplementation would improve
      biochemical abnormalities, visual function, and growth in affected individuals.
      METHODS: This was a randomized, double-blind, placebo-controlled trial conducted
      at a single center. Treatment groups received supplements of DHA (100 mg/kg per
      day). The primary outcome measures were the change from baseline in the visual
      function and physical growth during the 1 year follow-up period. RESULTS: Fifty
      individuals were enrolled and randomized. Two were subsequently excluded from
      study analysis when it was determined that they had a single enzyme disorder of
      peroxisomal beta oxidation. Thirty-four returned for follow-up. Nine patients
      died during the trial of their disorder, and 5 others were lost to follow-up. DHA
      supplementation was well tolerated. There was no difference in the outcomes
      between the treated and untreated groups in biochemical function,
      electroretinogram, or growth. Improvements were seen in both groups in certain
      individuals. CONCLUSIONS: DHA supplementation did not improve the visual function
      or growth of treated individuals with peroxisome assembly disorders.
      CLASSIFICATION OF EVIDENCE: This interventional study provides Class II evidence
      that DHA supplementation did not improve the visual function or growth of treated
      individuals with peroxisome assembly disorders during an average of 1 year of
      follow-up in patients aged 1 to 144 months.

PMID- 20805529
TI  - Immune reconstitution inflammatory syndrome after withdrawal of natalizumab?

PMID- 20805530
TI  - Spot sign and live-imaged dramatic intracerebral hematoma expansion.

PMID- 20805531
TI  - Dystonic drop foot gait in a patient with manganism.

PMID- 20805532
TI  - Teaching video neuroimages: involuntary muscle contractions in Hoffman syndrome.

PMID- 20805533
TI  - What is the risk of permanent disability from a multiple sclerosis relapse?

PMID- 20805534
TI  - Theta oscillations predict the detrimental effects of memory retrieval.
AB  - Retrieving a target item from episodic memory typically enhances later memory for
      the retrieved item but causes forgetting of competing irrelevant memories. This
      finding is termed retrieval-induced forgetting (RIF) and is assumed to be the
      consequence of an inhibitory mechanism resolving retrieval competition. In the
      present study, we examined brain oscillatory processes related to RIF, as induced
      by competitive memory retrieval. Contrasting a competitive with a noncompetitive
      retrieval condition, we found a stronger increase in early evoked theta (4-7 Hz)
      activity, which specifically predicted RIF, but not retrieval-induced
      enhancement. Within the cognitive framework of RIF, these findings suggest that
      theta oscillations reflect arising interference and its resolution during
      competitive retrieval in episodic memory. Supplemental materials for this article
      may be downloaded from http://cabn.psychonomic-journals.org/content/supplemental.

PMID- 20805535
TI  - Comparison of neural activity that leads to true memories, false memories, and
      forgetting: An fMRI study of the misinformation effect.
AB  - False memories can occur when people are exposed to misinformation about a past
      event. Of interest here are the neural mechanisms of this type of memory failure.
      In the present study, participants viewed photographic vignettes of common
      activities during an original event phase (OEP), while we monitored their brain
      activity using fMRI. Later, in a misinformation phase, participants viewed
      sentences describing the studied photographs, some of which contained information
      conflicting with that depicted in the photographs. One day later, participants
      returned for a surprise item memory recognition test for the content of the
      photographs. Results showed reliable creation of false memories, in that
      participants reported information that had been presented in the verbal
      misinformation but not in the photographs. Several regions were more active
      during the OEP for later accurate memory than for forgetting, but they were also
      more active for later false memories, indicating that false memories in this
      paradigm are not simply caused by failure to encode the original event. There was
      greater activation in the ventral visual stream for subsequent true memories than
      for subsequent false memories, however, suggesting that differences in encoding
      may contribute to later susceptibility to misinformation.

PMID- 20805536
TI  - Emotions in cognitive conflicts are not aversive but are task specific.
AB  - It has been suggested that cognitive conflicts require effortful processing and,
      therefore, are aversive (Botvinick, 2007). In the present study, we compared
      conflicts emerging from the inhibition of a predominant response tendency in a
      go/no-go task with those between incompatible response activations in a Simon
      task in a within-subjects design, using the same type of stimuli. Whereas no-go
      trials elicited reduced skin conductance and pupillometric responses, but
      prolonged corrugator muscle activity, as compared with go trials, incompatible
      and compatible Simon trials were indistinguishable with respect to these
      parameters. Furthermore, the conflict-sensitive N2 components of the event
      related brain potential were similar in amplitude, but showed significantly
      different scalp distributions, indicating dissociable neural generator systems.
      The present findings suggest the involvement of different emotional and cognitive
      processes in both types of cognitive conflicts-none being aversive, however. In
      addition, the N2 findings call into question claims of common monitoring systems
      for all kinds of cognitive conflicts.

PMID- 20805537
TI  - Adding fear to conflict: a general purpose cognitive control network is modulated
      by trait anxiety.
AB  - Studies of cognitive control show that the dorsal anterior cingulate cortex
      (dACC) and dorsolateral prefrontal cortex are involved in the detection and
      resolution of cognitive conflict. However, the neural and behavioral mechanisms
      underlying emotional interference effects are less consistent. We used fMRI
      during emotional and nonemotional versions of a facial Stroop task to investigate
      the effects of emotional stimuli on cognitive control. In the full group there
      was limited evidence that different prefrontal circuits manage conflict arising
      from emotional and nonemotional distractors. However, individual differences in
      trait anxiety affected both behavioral performance and neural activity during the
      emotional task. Relative to low-anxiety (LA) subjects, high-anxiety (HA) subjects
      showed greater amygdala activity to task-relevant emotional information and
      impaired performance and greater conflict-related activity in the dACC when
      emotional content was task-irrelevant. Only LA subjects activated rostral ACC
      during the emotional task. This is consistent with cognitive models of individual
      differences that hypothesize deficient control of task-irrelevant emotional
      information in HA subjects. Additional behavioral and fMRI results from this
      study may be downloaded from http://cabn.psychonomic
      journals.org/content/supplemental.

PMID- 20805538
TI  - Trait anxiety and dynamic adjustments in conflict processing.
AB  - Recently, it has been assumed that high- and low-trait-anxious subjects differ in
      the way they use fundamental cognitive control mechanisms. The present study was
      designed to further elucidate this topic by focusing on trial-to-trial
      adjustments in neuronal correlates of conflict processing. An
      electroencephalogram was recorded while subjects (N = 71) performed a gender
      discrimination version of the Stroop task. The conflict-related N400 of the ERP
      was influenced by an interaction between trait anxiety and previous trial
      context: An additional negative-going deflection in the N400 range was observed
      when the target-distractor pairing of the directly preceding trial was
      incongruent, but only in highly anxious subjects. Thus, highly anxious subjects
      appear to more strongly engage neuronal modules involved in conflict monitoring
      when previously exposed to a high stimulus-response conflict. These results
      indicate that trait anxiety is crucially linked to the way the cognitive system
      dynamically adapts to recent demands.

PMID- 20805539
TI  - Beyond risk and ambiguity: deciding under ignorance.
AB  - In this study, we examined the neural basis of decision making under different
      types of uncertainty that involve missing information: ambiguity (vague
      probabilities) and sample space ignorance (SSI; unknown outcomes). fMRI revealed
      that these two different types of uncertainty recruit distinct neural substrates:
      Ambiguity recruits the left insula, whereas SSI recruits the anterior cingulate
      cortex, bilateral inferior parietal cortex, and the lateral orbitofrontal cortex.
      The finding of unique activations for different types of uncertainty may not
      necessarily be predicted within the reductive approach of modern theories of
      decision making under uncertainty, because these theories purport that humans
      reduce more complicated uncertain environments to subjectively formed less
      complicated ones (i.e., SSI to ambiguity). The predictions of the reductive view
      held only for ambiguity-averse individuals and not for ambiguity-tolerant
      individuals. Consequently, theories of decision making under uncertainty should
      include individual tolerance for missing information and how these individual
      differences modulate the neural systems engaged during decision making.
      Supplemental materials for this article may be downloaded from
      http://cabn.psychonomic-journals.org/content/supplemental.

PMID- 20805540
TI  - Anterior insula activity predicts the influence of positively framed messages on
      decision making.
AB  - The neural mechanisms underlying the influence of persuasive messages on decision
      making are largely unknown. We address this issue using event-related fMRI to
      investigate how informative messages alter risk appraisal during choice.
      Participants performed the Iowa Gambling Task while viewing a positively framed,
      negatively framed, or control message about the options. The right anterior
      insula correlated with improvement in choice behavior due to the positively
      framed but not the negatively framed message. With the positively framed message,
      there was increased activation proportional to message effectiveness when less
      preferred options were chosen, consistent with a role in the prediction of
      adverse outcomes. In addition, the dorsomedial and the left dorsolateral
      prefrontal cortex correlated with overall decision quality, regardless of message
      type. The dorsomedial region mediated the relationship between the right anterior
      insula and decision quality with the positively framed messages. These findings
      suggest a network of frontal brain regions that integrate informative messages
      into the evaluation of options during decision making. Supplemental procedures
      and results for this article may be downloaded from http://cabn.psychonomic
      journals.org/content/supplemental.

PMID- 20805541
TI  - Regret and the negative evaluation of decision outcomes in major depression.
AB  - Disruption of normal emotional experience is central to the phenomenology of
      depression. Twenty-three depressed outpatients and 23 control subjects performed
      a computerized decision-making task, during which affective ratings were assessed
      online to identify various dimensions of emotional experience. We sought to
      contrast regret (the comparison of the outcomes of selected and nonselected
      options) with the general negative appraisal of task events. The experience of
      regret was reduced in depressed patients, an effect that was particularly related
      to self-reported apathy scores. In an exploratory analysis, we observed that
      females had a general downward shift in their ratings, as compared with males,
      but disappointment and regret effects were of similar magnitude. The possible
      contribution of the orbitofrontal cortex to the phenomenology of regret is
      discussed. Supplemental materials for this article may be downloaded from
      http://cabn.psychonomic-journals.org/content/supplemental.

PMID- 20805542
TI  - Subgenual cingulate cortex and personality in chimpanzees (Pan troglodytes).
AB  - Animals vary in their dispositions, abilities, and moods and demonstrate
      characteristic behavior patterns that remain consistent across situation and
      time. This study describes the relationship between measures of personality in
      the chimpanzee and the structure of the subgenual cingulate cortex (SGCC).
      Measures of individual traits and personality factors (dominance, extraversion,
      conscientiousness, and agreeableness) and assessments of percentage of SGCC gray
      matter (PGM) and asymmetry taken from MRI scans were obtained for 74 chimpanzees
      housed at the Yerkes National Primate Research Center. PGM in the SGCC was
      significantly higher for females than for males and was significantly correlated
      with two personality factors (dominance and conscientiousness) in male apes.
      There was also a population-level leftward asymmetry in the SGCC. These results
      are discussed in terms of current models of SGCC function, which suggest that
      this area may play a role in the biological foundation of personality.

PMID- 20805543
TI  - Differential neuronal responses to the self and others in the extrastriate body
      area and the fusiform body area.
AB  - The extrastriate body area (EBA) and the fusiform body area (FBA) are selectively
      activated by viewing human bodies. However, the role of these functionally
      defined brain areas in self-other discrimination is still unresolved. Thirty-one
      females were presented with 16 pictures of their own body and another body in a
      bikini and with scrambled images while fMRI was performed. Moreover, standardized
      stimulus material was used in order to localize the EBA and FBA. Region-of
      interest analysis showed an enhanced BOLD response to the self-images relative to
      the non-self-images in the right EBA and FBA. The right EBA and FBA are activated
      differently by viewing oneself and others and might thus play a role in visual
      self-other discrimination.

PMID- 20805544
TI  - Ethical decision making with end-of-life care: palliative sedation and
      withholding or withdrawing life-sustaining treatments.
AB  - Palliative sedation (PS) is the use of medications to induce decreased or absent
      awareness in order to relieve otherwise intractable suffering at the end of life.
      Although uncommon, some patients undergoing aggressive symptom control measures
      still have severe suffering from underlying disease or therapy-related adverse
      effects. In these circumstances, use of PS is considered. Although the goal is to
      provide relief in an ethically acceptable way to the patient, family, and health
      care team, health care professionals often voice concerns whether such treatment
      is necessary or whether such treatment equates to physician-assisted suicide or
      euthanasia. In this review, we frame clinical scenarios in which PS may be
      considered, summarize the ethical underpinnings of the practice, and further
      differentiate PS from other forms of end-of-life care, including withholding
      and/or withdrawing life-sustaining therapy and physician-assisted suicide and
      euthanasia.

PMID- 20805545
TI  - Importance of early exposure to clinical research for osteopathic medical
      students.

PMID- 20805546
TI  - Understanding insurance: will a public option or co-op get us where we want?

PMID- 20805547
TI  - Was the FDA misled by JUPITER?

PMID- 20805548
TI  - Cost-effectiveness of rosuvastatin for primary prevention of cardiovascular
      events according to Framingham Risk Score in patients with elevated C-reactive
      protein.
AB  - CONTEXT: The Food and Drug Administration (FDA) recently approved rosuvastatin
      calcium for prevention of cardiovascular events in patients who have elevated
      levels of high-sensitivity C-reactive protein (hs-CRP) but not overt
      hyperlipidemia. The FDA's decision was based primarily on research reported by
      the JUPITER (Justification for the Use of Statins in Prevention: An Intervention
      Trial Evaluating Rosuvastatin) Study Group. The cost-effectiveness of such
      treatment is unknown. OBJECTIVE: To compare the cost-effectiveness of treatment
      with rosuvastatin vs standard management, according to Framingham Risk Score
      (FRS), for the primary prevention of cardiovascular events in patients who have
      hs-CRP levels of 2.0 mg/L or higher and low-density lipoprotein cholesterol (LDL
      C) levels of less than 130 mg/dL. METHODS: A Markov-type model was used to
      calculate the incremental cost-effectiveness ratio of rosuvastatin (20 mg daily)
      vs standard management for the primary prevention of cardiovascular events in
      patients over a 10-year period. Cost data were obtained from the Centers for
      Medicare & Medicaid Services and the Red Book drug reference. Health utility
      measures were obtained from the literature. Cardiovascular event data were
      obtained directly from the JUPITER Study Group. One-way sensitivity analysis and
      probabilistic sensitivity analysis were conducted. RESULTS: Treating patients
      with rosuvastatin to prevent cardiovascular events based on a hs-CRP level
      greater than 2.0 mg/L and an LDL-C level of 130 mg/dL or lower would result in
      estimated incremental cost-effectiveness ratios of $35,455 per quality-adjusted
      life year (QALY) in patients with an FRS greater than 10% and $90,714 per QALY in
      patients with an FRS less than or equal to 10%. Results of probabilistic
      sensitivity analysis suggested that in patients with an FRS greater than 10%, the
      probability that rosuvastatin is considered cost-effective at $50,000 per QALY is
      approximately 98%. In patients with an FRS less than or equal to 10%, the
      probability that rosuvastatin is considered cost-effective at $50,000 per QALY is
      0%. CONCLUSIONS: Compared with standard management, treatment with rosuvastatin
      is a cost-effective strategy over a 10-year period for preventing cardiovascular
      events in patients with FRS greater than 10%, elevated hs-CRP levels, and normal
      LDL-C levels.

PMID- 20805549
TI  - Constipation-predominant irritable bowel syndrome complicating asymptomatic
      nonrotation of the midgut.
AB  - Nonrotation is a part of the spectrum of anatomic anomalies comprising
      malrotation. Most cases of nonrotation are symptomatic and managed surgically
      with a Ladd's procedure. However, incidental discovery of asymptomatic patients
      has also been reported. In these cases, the role of surgery is debated. The
      authors describe a case of nonrotation in a young woman with constipation
      predominant irritable bowel syndrome that caused symptoms associated with
      nonrotation. Medical management of her irritable bowel syndrome resulted in the
      resolution of all abdominal complaints and a Ladd's procedure was not
      recommended. The authors include a literature review of nonrotation with an
      emphasis on the treatment of asymptomatic disease.

PMID- 20805550
TI  - Delayed diagnosis of neuroborreliosis presenting as bell palsy and meningitis.
AB  - Lyme disease is most prevalent in the northeast and upper Midwest regions of the
      United States. While early symptoms may be mild (eg, rash, flu-like symptoms,
      joint pain), late or persistent infection can cause chronic neurologic
      impairments. Because of this range of symptoms, physicians can have difficulty
      diagnosing Lyme disease, especially in the absence of erythema chronicum migrans.
      We report a case of a woman who initially presented with severe vertigo and
      vomiting and later with fever, headache, and facial droop. After more than 3
      weeks of misdiagnosis, the patient tested positive for Lyme disease and was
      diagnosed as having neuroborreliosis presenting as Bell palsy and meningitis. The
      authors review the history, diagnosis, and management of Lyme disease.

PMID- 20805552
TI  - Importance of obtaining a detailed medical history in diagnosing emphysematous
      cystitis.

PMID- 20805553
TI  - Avoidance of long mononucleotide repeats in codon pair usage.
AB  - Protein is an essential component for life, and its synthesis is mediated by
      codons in any organisms on earth. While some codons encode the same amino acid,
      their usage is often highly biased. There are many factors that can cause the
      bias, but a potential effect of mononucleotide repeats, which are known to be
      highly mutable, on codon usage and codon pair preference is largely unknown. In
      this study we performed a genomic survey on the relationship between
      mononucleotide repeats and codon pair bias in 53 bacteria, 68 archaea, and 13
      eukaryotes. By distinguishing the codon pair bias from the codon usage bias, four
      general patterns were revealed: strong avoidance of five or six mononucleotide
      repeats in codon pairs; lower observed/expected (o/e) ratio for codon pairs with
      C or G repeats (C/G pairs) than that with A or T repeats (A/T pairs); a negative
      correlation between genomic GC contents and the o/e ratios, particularly for C/G
      pairs; and avoidance of C/G pairs in highly conserved genes. These results
      support natural selection against long mononucleotide repeats, which could induce
      frameshift mutations in coding sequences. The fact that these patterns are found
      in all kingdoms of life suggests that this is a general phenomenon in living
      organisms. Thus, long mononucleotide repeats may play an important role in base
      composition and genetic stability of a gene and gene functions.

PMID- 20805554
TI  - Genetic differentiation, clinal variation and phenotypic associations with growth
      cessation across the Populus tremula photoperiodic pathway.
AB  - Perennial plants monitor seasonal changes through changes in environmental
      conditions such as the quantity and quality of light. To ensure a correct
      initiation of critical developmental processes, such as the initiation and
      cessation of growth, plants have adapted to a spatially variable light regime and
      genes in the photoperiodic pathway have been implicated as likely sources for
      these adaptations. Here we examine genetic variation in genes from the
      photoperiodic pathway in Populus tremula (Salicaceae) for signatures diversifying
      selection in response to varying light regimes across a latitudinal gradient. We
      fail to identify any loci with unusually high levels of genetic differentiation
      among populations despite identifying four SNPs that show significant allele
      frequency clines with latitude. We do, however, observe large covariance in
      allelic effects across populations for growth cessation, a highly adaptive trait
      in P. tremula. High covariance in allelic effects is a signature compatible with
      diversifying selection along an environmental gradient. We also observe
      significantly higher heterogeneity in genetic differentiation among SNPs from the
      photoperiod genes than among SNPs from randomly chosen genes. This suggests that
      spatially variable selection could be affecting genes from the photoperiod
      pathway even if selection is not strong enough to cause individual loci to be
      identified as outliers. SNPs from three genes in the photoperiod pathway (PHYB2,
      LHY1, and LHY2) show significant associations with natural variation in growth
      cessation. Collectively these SNPs explain 10-15% of the phenotypic variation in
      growth cessation. Covariances in allelic effects across populations help explain
      an additional 5-7% of the phenotypic variation in growth cessation.

PMID- 20805555
TI  - Different aneuploidies arise from the same bridge-induced chromosomal
      translocation event in Saccharomyces cerevisiae.
AB  - Chromosome translocations are gross chromosomal rearrangements that have often
      been associated with cancer development in mammalian cells. The feasibility of
      drastically reshaping the genome with a single translocation event also gives
      this molecular event a powerful capacity to drive evolution. Despite these
      implications and their role in genome instability, very little is known about the
      molecular mechanisms that promote and accompany these events. Here, at the
      molecular level, we describe 10 morphologically and physiologically different
      translocants ensuing from the induction of the same bridge-induced translocation
      (BIT) event in the budding yeast Saccharomyces cerevisiae. We have demonstrated
      that, despite their common origin from the integration of the same linear DNA
      construct, all 10 translocation mutant strains have different phenotypes and the
      ability to sporulate and regulate gene expression and morphology. We also provide
      insights into how heterogeneous phenotypic variations originate from the same
      initial genomic event. Here we show eight different ways in which yeast cells
      have dealt with a single initial event inducing translocation. Our results are in
      agreement with the formation of complex rearrangements and abnormal karyotypes
      described in many leukemia patients, thus confirming the modellistic value of the
      yeast BIT system for mammalian cells.

PMID- 20805556
TI  - Genetics of extracellular matrix remodeling during organ growth using the
      Caenorhabditis elegans pharynx model.
AB  - The organs of animal embryos are typically covered with an extracellular matrix
      (ECM) that must be carefully remodeled as these organs enlarge during post
      embryonic growth; otherwise, their shape and functions may be compromised. We
      previously described the twisting of the Caenorhabditis elegans pharynx (here
      called the Twp phenotype) as a quantitative mutant phenotype that worsens as that
      organ enlarges during growth. Mutations previously known to cause pharyngeal
      twist affect membrane proteins with large extracellular domains (DIG-1 and SAX
      7), as well as a C. elegans septin (UNC-61). Here we show that two novel alleles
      of the C. elegans papilin gene, mig-6(et4) and mig-6(sa580), can also cause the
      Twp phenotype. We also show that overexpression of the ADAMTS protease gene mig
      17 can suppress the pharyngeal twist in mig-6 mutants and identify several
      alleles of other ECM-related genes that can cause or influence the Twp phenotype,
      including alleles of fibulin (fbl-1), perlecan (unc-52), collagens (cle-1, dpy
      7), laminins (lam-1, lam-3), one ADAM protease (sup-17), and one ADAMTS protease
      (adt-1). The Twp phenotype in C. elegans is easily monitored using light
      microscopy, is quantitative via measurements of the torsion angle, and reveals
      that ECM components, metalloproteinases, and ECM attachment molecules are
      important for this organ to retain its correct shape during post-embryonic
      growth. The Twp phenotype is therefore a promising experimental system to study
      ECM remodeling and diseases.

PMID- 20805558
TI  - Mapping environment-specific quantitative trait loci.
AB  - Environment-specific quantitative trait loci (QTL) refer to QTL that express
      differently in different environments, a phenomenon called QTL-by-environment (Q
      * E) interaction. Q * E interaction is a difficult problem extended from
      traditional QTL mapping. The mixture model maximum-likelihood method is commonly
      adopted for interval mapping of QTL, but the method is not optimal in handling
      QTL interacting with environments. We partitioned QTL effects into main and
      interaction effects. The main effects are represented by the means of QTL effects
      in all environments and the interaction effects are represented by the variances
      of the QTL effects across environments. We used the Markov chain Monte Carlo
      (MCMC) implemented Bayesian method to estimate both the main and the interaction
      effects. The residual error covariance matrix was modeled using the factor
      analytic covariance structure. A simulation study showed that the factor analytic
      structure is robust and can handle other structures as special cases. The method
      was also applied to Q * E interaction mapping for the yield trait of barley.
      Eight markers showed significant main effects and 18 markers showed significant Q
      * E interaction. The 18 interacting markers were distributed across all seven
      chromosomes of the entire genome. Only 1 marker had both the main and the Q * E
      interaction effects. Each of the other markers had either a main effect or a Q *
      E interaction effect but not both.

PMID- 20805557
TI  - Genetic mechanisms of coffee extract protection in a Caenorhabditis elegans model
      of beta-amyloid peptide toxicity.
AB  - Epidemiological studies have reported that coffee and/or caffeine consumption may
      reduce Alzheimer's disease (AD) risk. We found that coffee extracts can similarly
      protect against beta-amyloid peptide (Abeta) toxicity in a transgenic
      Caenorhabditis elegans Alzheimer's disease model. The primary protective
      component(s) in this model is not caffeine, although caffeine by itself can show
      moderate protection. Coffee exposure did not decrease Abeta transgene expression
      and did not need to be present during Abeta induction to convey protection,
      suggesting that coffee exposure protection might act by activating a protective
      pathway. By screening the effects of coffee on a series of transgenic C. elegans
      stress reporter strains, we identified activation of the skn-1 (Nrf2 in mammals)
      transcription factor as a potential mechanism of coffee extract protection.
      Inactivation of skn-1 genetically or by RNAi strongly blocked the protective
      effects of coffee extract, indicating that activation of the skn-1 pathway was
      the primary mechanism of coffee protection. Coffee also protected against
      toxicity resulting from an aggregating form of green fluorescent protein (GFP) in
      a skn-1-dependent manner. These results suggest that the reported protective
      effects of coffee in multiple neurodegenerative diseases may result from a
      general activation of the Nrf2 phase II detoxification pathway.

PMID- 20805559
TI  - Extended Bayesian LASSO for multiple quantitative trait loci mapping and
      unobserved phenotype prediction.
AB  - The Bayesian LASSO (BL) has been pointed out to be an effective approach to
      sparse model representation and successfully applied to quantitative trait loci
      (QTL) mapping and genomic breeding value (GBV) estimation using genome-wide dense
      sets of markers. However, the BL relies on a single parameter known as the
      regularization parameter to simultaneously control the overall model sparsity and
      the shrinkage of individual covariate effects. This may be idealistic when
      dealing with a large number of predictors whose effect sizes may differ by orders
      of magnitude. Here we propose the extended Bayesian LASSO (EBL) for QTL mapping
      and unobserved phenotype prediction, which introduces an additional level to the
      hierarchical specification of the BL to explicitly separate out these two model
      features. Compared to the adaptiveness of the BL, the EBL is "doubly adaptive"
      and thus, more robust to tuning. In simulations, the EBL outperformed the BL in
      regard to the accuracy of both effect size estimates and phenotypic value
      predictions, with comparable computational time. Moreover, the EBL proved to be
      less sensitive to tuning than the related Bayesian adaptive LASSO (BAL), which
      introduces locus-specific regularization parameters as well, but involves no
      mechanism for distinguishing between model sparsity and parameter shrinkage.
      Consequently, the EBL seems to point to a new direction for QTL mapping,
      phenotype prediction, and GBV estimation.

PMID- 20805560
TI  - Next generation sequencing for clinical diagnostics-principles and application to
      targeted resequencing for hypertrophic cardiomyopathy: a paper from the 2009
      William Beaumont Hospital Symposium on Molecular Pathology.
AB  - During the past five years, new high-throughput DNA sequencing technologies have
      emerged; these technologies are collectively referred to as next generation
      sequencing (NGS). By virtue of sequencing clonally amplified DNA templates or
      single DNA molecules in a massively parallel fashion in a flow cell, NGS provides
      both qualitative and quantitative sequence data. This combination of information
      has made NGS the technology of choice for complex genetic analyses that were
      previously either technically infeasible or cost prohibitive. As a result, NGS
      has had a fundamental and broad impact on many facets of biomedical research. In
      contrast, the dissemination of NGS into the clinical diagnostic realm is in its
      early stages. Though NGS is powerful and can be envisioned to have multiple
      applications in clinical diagnostics, the technology is currently complex.
      Successful adoption of NGS into the clinical laboratory will require expertise in
      both molecular biology techniques and bioinformatics. The current report presents
      principles that underlie NGS including sequencing library preparation, sequencing
      chemistries, and an introduction to NGS data analysis. These concepts are
      subsequently further illustrated by showing representative results from a case
      study using NGS for targeted resequencing of genes implicated in hypertrophic
      cardiomyopathy.

PMID- 20805561
TI  - Rapid detection of the epidermal growth factor receptor mutation in non-small
      cell lung cancer for analysis of acquired resistance using molecular beacons.
AB  - A secondary mutation (T790M) in epidermal growth factor receptor (EGFR) is a
      hallmark of acquired resistance to EGFR inhibitors used to treat non-small-cell
      lung cancer (NSCLC). Therefore, identifying the T790M mutation is crucial to
      guide treatment decisions. Given that DNA sequencing methods are time-consuming
      and insensitive, we developed and investigated the feasibility of using molecular
      beacons for the detection of the T790M mutation in EGFR. A molecular beacon
      complementary to the region of the secondary EGFR mutation (T790M) was designed
      and used in NSCLC samples bearing drug-sensitive and -resistant EGFR mutations.
      For a rapid and simple assay, we attempted to use the molecular beacon with real
      time PCR and in situ fluorescence imaging. The ability of the designed molecular
      beacon to specifically detect the T790M mutation of EGFR was tested for samples
      from two patients with drug resistance and compared with conventional DNA
      sequencing methods. The molecular beacon successfully detected the T790M mutation
      in patient samples with drug resistance. The sensitivity of the molecular beacon,
      which detected as little as 2% of genomic DNA from the drug-resistant cells
      (H1975), was much higher than direct sequencing. Furthermore, in situ
      fluorescence imaging with the molecular beacon gave rise to a distinguishable
      signal for the T790M mutation in drug-resistant cells. The molecular beacon-based
      approach enabled rapid and sensitive detection of the EGFR mutation (T790M) in
      NSCLC with in situ fluorescence imaging, which can be directed to determine
      various treatment options in patients with cancer.

PMID- 20805562
TI  - IL-10 inhibits transcription elongation of the human TNF gene in primary
      macrophages.
AB  - IL-10 plays a central nonredundant role in limiting inflammation in vivo.
      However, the mechanisms involved remain to be resolved. Using primary human
      macrophages, we found that IL-10 inhibits selected inflammatory genes, primarily
      at a level of transcription. At the TNF gene, this occurs not through an
      inhibition of RNA polymerase II (Pol II) recruitment and transcription initiation
      but through a mechanism targeting the stimulation of transcription elongation by
      cyclin-dependent kinase (CDK) 9. We demonstrated an unanticipated requirement for
      a region downstream of the TNF 3' untranslated region (UTR) that contains the
      nuclear factor kappaB (NF-kappaB) binding motif (kappaB4) both for induction of
      transcription by lipopolysaccharide (LPS) and its inhibition by IL-10. IL-10 not
      only inhibits the recruitment of RelA to regions containing kappaB sites at the
      TNF gene but also to those found at other LPS-induced genes. We show that
      although IL-10 elicits a general block in RelA recruitment to its genomic
      targets, the gene-specific nature of IL-10's actions are defined through the
      differential recruitment of CDK9 and the control of transcription elongation. At
      TNF, but not NFKBIA, the consequence of RelA recruitment inhibition is a loss of
      CDK9 recruitment, preventing the stimulation of transcription elongation.

PMID- 20805563
TI  - Somatic hypermutation as a generator of antinuclear antibodies in a murine model
      of systemic autoimmunity.
AB  - Systemic lupus erythematosus (SLE) is characterized by high-avidity IgG
      antinuclear antibodies (ANAs) that are almost certainly products of T cell
      dependent immune responses. Whether critical amino acids in the third
      complementarity-determining region (CDR3) of the ANA originate from V(D)J
      recombination or somatic hypermutation (SHM) is not known. We studied a mouse
      model of SLE in which all somatic mutations within ANA V regions, including those
      in CDR3, could be unequivocally identified. Mutation reversion analyses revealed
      that ANA arose predominantly from nonautoreactive B cells that diversified
      immunoglobulin genes via SHM. The resolution afforded by this model allowed us to
      demonstrate that one ANA clone was generated by SHM after a V(H) gene replacement
      event. Mutations producing arginine substitutions were frequent and arose largely
      (66%) from base changes in just two codons: AGC and AGT. These codons are
      abundant in the repertoires of mouse and human V genes. Our findings reveal the
      predominant role of SHM in the development of ANA and underscore the importance
      of self-tolerance checkpoints at the postmutational stage of B cell
      differentiation.

PMID- 20805565
TI  - Sliding set-points of immune responses for therapy of autoimmunity.
AB  - Although recent developments in the treatment of autoimmune disease have
      dramatically improved patient outcomes, these medications are not curative. Two
      studies in this issue demonstrate the feasibility of curing spontaneous
      autoimmunity in animal models via short-term enhancement of naturally arising
      regulatory T (T reg) cells, a subset of CD4+ T cells needed for maintaining self
      tolerance. Importantly, these therapies seemed to generate a new equilibrium, or
      "set-point," at which self-tissue damage no longer occurred long after the drug
      was eliminated from the body.

PMID- 20805564
TI  - Find-me and eat-me signals in apoptotic cell clearance: progress and conundrums.
AB  - Everyday we turnover billions of cells. The quick, efficient, and immunologically
      silent disposal of the dying cells requires a coordinated orchestration of
      multiple steps, through which phagocytes selectively recognize and engulf
      apoptotic cells. Recent studies have suggested an important role for soluble
      mediators released by apoptotic cells that attract phagocytes ("find-me"
      signals). New information has also emerged on multiple receptors that can
      recognize phosphatidylserine, the key "eat-me" signal exposed on the surface of
      apoptotic cells. This perspective discusses recent exciting progress, gaps in our
      understanding, and the conflicting issues that arise from the newly acquired
      knowledge.

PMID- 20805566
TI  - Benefits and risks of iron supplementation in anemic neonatal pigs.
AB  - Iron deficiency is a common health problem. The most severe consequence of this
      disorder is iron deficiency anemia (IDA), which is considered the most common
      nutritional deficiency worldwide. Newborn piglets are an ideal model to explore
      the multifaceted etiology of IDA in mammals, as IDA is the most prevalent
      deficiency disorder throughout the early postnatal period in this species and
      frequently develops into a critical illness. Here, we report the very low
      expression of duodenal iron transporters in pigs during the first days of life.
      We postulate that this low expression level is why the iron demands of the piglet
      body are not met by iron absorption during this period. Interestingly, we found
      that a low level of duodenal divalent metal transporter 1 and ferroportin, two
      iron transporters located on the apical and basolateral membrane of duodenal
      absorptive enterocytes, respectively, correlates with abnormally high expression
      of hepcidin, despite the poor hepatic and overall iron status of these animals.
      Parenteral iron supplementation by a unique intramuscular administration of large
      amounts of iron dextran is current practice for the treatment of IDA in piglets.
      However, the potential toxicity of such supplemental iron implies the necessity
      for caution when applying this treatment. Here we demonstrate that a modified
      strategy for iron supplementation of newborn piglets with iron dextran improves
      the piglets' hematological status, attenuates the induction of hepcidin
      expression, and minimizes the toxicity of the administered iron.

PMID- 20805567
TI  - Interpretations of fundus autofluorescence from studies of the bisretinoids of
      the retina.

PMID- 20805568
TI  - Altered ferritin subunit composition: change in iron metabolism in lens
      epithelial cells and downstream effects on glutathione levels and VEGF secretion.
AB  - PURPOSE: The iron storage protein ferritin is necessary for the safe storage of
      iron and for protection against the production of iron-catalyzed oxidative
      damage. Ferritin is composed of 24 subunits of two types: heavy (H) and light
      (L). The ratio of these subunits is tissue specific, and alteration of this ratio
      can have profound effects on iron storage and availability. In the present study,
      siRNA for each of the chains was used to alter the ferritin H:L chain ratio and
      to determine the effect of these changes on ferritin synthesis, iron metabolism,
      and downstream effects on iron-responsive pathways in canine lens epithelial
      cells. METHODS: Primary cultures of canine lens epithelial cells were used. The
      cells were transfected with custom-made siRNA for canine ferritin H- and L
      chains. De novo ferritin synthesis was determined by labeling newly synthesized
      ferritin chains with 35S-methionine, immunoprecipitation, and separation by SDS
      PAGE. Iron uptake into cells and incorporation into ferritin was measured by
      incubating the cells with 59Fe-labeled transferrin. Western blot analysis was
      used to determine the presence of transferrin receptor, and ELISA was used to
      determine total ferritin concentration. Ferritin localization in the cells was
      determined by immunofluorescence labeling. VEGF, glutathione secretion levels,
      and cystine uptake were measured. RESULTS: FHsiRNA decreased ferritin H-chain
      synthesis, but doubled ferritin L-chain synthesis. FLsiRNA decreased both
      ferritin H- and L-chain synthesis. The degradation of ferritin H-chain was
      blocked by both siRNAs, whereas only FHsiRNA blocked the degradation of ferritin
      L-chain, which caused significant accumulation of ferritin L-chain in the cells.
      This excess ferritin L-chain was found in inclusion bodies, some of which were co
      localized with lysosomes. Iron storage in ferritin was greatly reduced by
      FHsiRNA, resulting in increased iron availability, as noted by a decrease in
      transferrin receptor levels and iron uptake from transferrin. Increased iron
      availability also increased cystine uptake and glutathione concentration and
      decreased nuclear translocation of hypoxia-inducible factor 1-alpha and vascular
      endothelial growth factor (VEGF) accumulation in the cell-conditioned medium.
      CONCLUSIONS: Most of the effects of altering the ferritin H:L ratio with the
      specific siRNAs were due to changes in the availability of iron in a labile pool.
      They caused significant changes in iron uptake and storage, the rate of ferritin
      synthesis and degradation, the secretion of VEGF, and the levels of glutathione
      in cultured lens epithelial cells. These profound effects clearly demonstrate
      that maintenance of a specific H:L ratio is part of a basic cellular homeostatic
      mechanism.

PMID- 20805569
TI  - C-reactive protein, body mass index, and diabetic retinopathy.
AB  - PURPOSE: C-reactive protein (CRP) is an inflammatory biomarker that may be
      associated with diabetic retinopathy (DR), but body mass index (BMI) is an
      important confounder of this relationship. The purpose of this study was to
      determine the relationship between CRP, BMI, and existing DR. METHODS: This was a
      population-based, cross-sectional study on 718 persons with diabetes in the
      Singapore Malay Eye Study (SiMES). Diabetes was defined as random glucose>or=11.1
      mmol/L, on diabetic medication or a history of physician-diagnosed diabetes. CRP
      was measured in frozen plasma. DR was graded from retinal photographs. RESULTS:
      Higher CRP and BMI were associated with lower prevalence of DR. After adjustment
      for age, sex, HbA1c level, hypertension, smoking, total cholesterol level,
      cholesterol-lowering medication, and insulin use, persons with the highest
      quartiles of CRP were less likely to have any DR (odds ratio [OR] 0.5; 95% CI,
      0.3-0.9, comparing the fourth with the first quartile of CRP), vision-threatening
      DR (OR 0.3; 95% CI, 0.1-0.7), or CSME (OR 0.2; 95% CI, 0.1-0.6). Similarly,
      persons with the highest quartiles of BMI were less likely to have any DR (OR
      0.5; 95% CI, 0.3-0.7), moderate DR (OR 0.4; 95% CI, 0.2-0.7), vision-threatening
      DR (OR 0.4; 95% CI, 0.1-0.8) or CSME (OR 0.2; 95% CI, 0.0-1.0). No significant
      interactions between CRP and BMI on DR were seen. CONCLUSIONS: Persons with
      diabetes who had higher levels of CRP and BMI were less likely to have DR.
      Further research is needed to understand the interrelationship role of
      inflammation, body weight, and microvascular complications.

PMID- 20805570
TI  - Automated software analysis of corneal micrographs for peripheral neuropathy.
AB  - PURPOSE: A relationship has been reported between the presence of peripheral
      neuropathy and the density and shape of corneal nerve fibers. Peripheral
      neuropathy is a debilitating condition that arises from many common health
      problems, and its presence is often confirmed with an invasive clinical test
      called intramuscular electromyography (EMG). In this study, the possibility of
      developing an alternative or adjunct test to EMG based on the appearance of nerve
      fibers in corneal micrographs was explored. Since corneal imaging is virtually
      noninvasive compared with EMG, such a test may be administered more liberally and
      frequently, before neuropathy symptoms occur. METHODS: A software program that
      automatically traces nerve fibers in corneal micrographs and generates measures
      based on these traces was implemented. This software was applied to a database of
      images collected by confocal laser scanning corneal microscopy from diabetic
      subjects whose levels of neuropathy were measured with EMG and from healthy
      subjects. RESULTS: Trends in the nerve fiber density and various measures of
      shape were calculated and observed, to explore the possibility of using these
      measures as a clinical tool for corroborating symptoms, confirming an evaluation,
      or evaluating risk factors for developing neuropathy. CONCLUSIONS: Preliminary
      statistical trends show a potential for measuring and observing neuropathy
      severity or for providing an objective risk measure for a patient's ensuing
      condition. More work is needed in the development of the measures and in their
      testing to prove that the measures can be made repeatable in a clinical
      environment.

PMID- 20805571
TI  - The role of crumbs genes in the vertebrate cornea.
AB  - PURPOSE: To evaluate the role of crumbs genes and related epithelial polarity
      loci in the vertebrate cornea. METHODS: The authors used histologic analysis and
      electron microscopy to evaluate the corneas of zebrafish mutant for a crumbs
      locus oko meduzy (ome) and in mutants of four other loci, nagie oko (nok), heart
      and soul (has), mosaic eyes (moe), and ncad (formerly glass onion), that function
      in the same or related genetic pathways. In parallel, they performed an
      evaluation of corneas in human carriers of a crumbs gene, CRB1, and mutations
      using topography and biomicroscopy. The expression of the CRB1 gene in the normal
      human cornea was examined by polymerase chain reaction (PCR) and
      immunohistochemical staining. RESULTS: The corneas of zebrafish mutants display
      severe abnormalities of the epithelial and stromal layers. The epithelial cells
      do not properly adhere to each other, and fluid-filled spaces form between them.
      In addition, the layering of the corneal stroma is poorly formed or absent. The
      corneas of human carriers of CRB1 mutations display shape deviations compared
      with what has been observed in normal individuals. A PCR product of the correct
      size was obtained from normal human corneal samples. Sequence analyses confirmed
      its identity to be the human CRB1 gene. Immunohistochemical staining using anti
      CRB1 yielded positive brown deposits in the human cornea. CONCLUSIONS: crumbs
      genes play a role in the differentiation of the vertebrate cornea. Corneal
      defects associated with crumbs gene mutations are very severe in the zebrafish
      model and, in comparison, appear clinically less pronounced in the human eye.

PMID- 20805572
TI  - Post-tetanic potentiation involves the presynaptic binding of calcium to
      calmodulin.

PMID- 20805573
TI  - Post-tetanic increase in the fast-releasing synaptic vesicle pool at the expense
      of the slowly releasing pool.
AB  - Post-tetanic potentiation (PTP) at the calyx of Held synapse is caused by
      increases not only in release probability (P(r)) but also in the readily
      releasable pool size estimated from a cumulative plot of excitatory post-synaptic
      current amplitudes (RRP(cum)), which contribute to the augmentation phase and the
      late phase of PTP, respectively. The vesicle pool dynamics underlying the latter
      has not been investigated, because PTP is abolished by presynaptic whole-cell
      patch clamp. We found that supplement of recombinant calmodulin to the
      presynaptic pipette solution rescued the increase in the RRP(cum) after high
      frequency stimulation (100 Hz for 4-s duration, HFS), but not the increase in
      P(r). Release-competent synaptic vesicles (SVs) are heterogeneous in their
      releasing kinetics. To investigate post-tetanic changes of fast and slowly
      releasing SV pool (FRP and SRP) sizes, we estimated quantal release rates before
      and 40 s after HFS using the deconvolution method. After HFS, the FRP size
      increased by 19.1% and the SRP size decreased by 25.4%, whereas the sum of FRP
      and SRP sizes did not increase. Similar changes in the RRP were induced by a
      single long depolarizing pulse (100 ms). The post-tetanic complementary changes
      of FRP and SRP sizes were abolished by inhibitors of myosin II or myosin light
      chain kinase. The post-tetanic increase in the FRP size coupled to a decrease in
      the SRP size provides the first line of evidence for the idea that a slowly
      releasing SV can be converted to a fast releasing one.

PMID- 20805574
TI  - Arrangement of Kv1 alpha subunits dictates sensitivity to tetraethylammonium.
AB  - Shaker-related Kv1 channels contain four channel-forming alpha subunits.
      Subfamily member Kv1.1 often occurs oligomerized with Kv1.2 alpha subunits in
      synaptic membranes, and so information was sought on the influence of their
      positions within tetramers on the channels' properties. Kv1.1 and 1.2 alpha genes
      were tandem linked in various arrangements, followed by expression as single
      chain proteins in mammalian cells. As some concatenations reported previously
      seemed not to reliably position Kv1 subunits in their assemblies, the identity of
      expressed channels was methodically evaluated. Surface protein, isolated by
      biotinylation of intact transiently transfected HEK-293 cells, gave Kv1.1/1.2
      reactivity on immunoblots with electrophoretic mobilities corresponding to full
      length concatenated tetramers. There was no evidence of protein degradation,
      indicating that concatemers were delivered intact to the plasmalemma. Constructs
      with like genes adjacent (Kv1.1-1.1-1.2-1.2 or Kv1.2-1.2-1.1-1.1) yielded delayed
      rectifying, voltage-dependent K(+) currents with activation parameters and
      inactivation kinetics slightly different from the diagonally positioned genes
      (Kv1.1-1.2-1.1-1.2 or 1.2-1.1-1.2-1.1). Pore-blocking petidergic toxins, alpha
      dendrotoxin, agitoxin-1, tityustoxin-Kalpha, and kaliotoxin, were unable to
      distinguish between the adjacent and diagonal concatamers. Unprecedentedly,
      external application of the pore-blocker tetraethylammonium (TEA) differentially
      inhibited the adjacent versus diagonal subunit arrangements, with diagonal
      constructs having enhanced susceptibility. Concatenation did not directly alter
      the sensitivities of homomeric Kv1.1 or 1.2 channels to TEA or the toxins. TEA
      inhibition of currents generated by channels made up from dimers (Kv1.1-1.2
      and/or Kv1.2-1.1) was similar to the adjacently arranged constructs. These
      collective findings indicate that assembly of alpha subunits can be directed by
      this optimized concatenation, and that subunit arrangement in heteromeric Kv
      channels affects TEA affinity.

PMID- 20805575
TI  - Dual roles of the sixth transmembrane segment of the CFTR chloride channel in
      gating and permeation.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is the only member of
      the adenosine triphosphate-binding cassette (ABC) transporter superfamily that
      functions as a chloride channel. Previous work has suggested that the external
      side of the sixth transmembrane segment (TM6) plays an important role in
      governing chloride permeation, but the function of the internal side remains
      relatively obscure. Here, on a cysless background, we performed cysteine-scanning
      mutagenesis and modification to screen the entire TM6 with intracellularly
      applied thiol-specific methanethiosulfonate reagents. Single-channel amplitude
      was reduced in seven cysteine-substituted mutants, suggesting a role of these
      residues in maintaining the pore structure for normal ion permeation. The
      reactivity pattern of differently charged reagents suggests that the cytoplasmic
      part of TM6 assumes a secondary structure of an alpha helix, and that reactive
      sites (341, 344, 345, 348, 352, and 353) reside in two neighboring faces of the
      helix. Although, as expected, modification by negatively charged reagents
      inhibits anion permeation, interestingly, modification by positively charged
      reagents of cysteine thiolates on one face (344, 348, and 352) of the helix
      affects gating. For I344C and M348C, the open time was prolonged and the closed
      time was shortened after modification, suggesting that depositions of positive
      charges at these positions stabilize the open state but destabilize the closed
      state. For R352C, which exhibited reduced single-channel amplitude, modifications
      by two positively charged reagents with different chemical properties completely
      restored the single-channel amplitude but had distinct effects on both the open
      time and the closed time. These results corroborate the idea that a helix
      rotation of TM6, which has been proposed to be part of the molecular motions
      during transport cycles in other ABC transporters, is associated with gating of
      the CFTR pore.

PMID- 20805576
TI  - A regulatory calcium-binding site at the subunit interface of CLC-K kidney
      chloride channels.
AB  - The two human CLC Cl(-) channels, ClC-Ka and ClC-Kb, are almost exclusively
      expressed in kidney and inner ear epithelia. Mutations in the genes coding for
      ClC-Kb and barttin, an essential CLC-K channel beta subunit, lead to Bartter
      syndrome. We performed a biophysical analysis of the modulatory effect of
      extracellular Ca(2+) and H(+) on ClC-Ka and ClC-Kb in Xenopus oocytes. Currents
      increased with increasing [Ca(2+)](ext) without full saturation up to 50 mM.
      However, in the absence of Ca(2+), ClC-Ka currents were still 20% of currents in
      10 mM [Ca(2+)](ext), demonstrating that Ca(2+) is not strictly essential for
      opening. Vice versa, ClC-Ka and ClC-Kb were blocked by increasing [H(+)](ext)
      with a practically complete block at pH 6. Ca(2+) and H(+) act as gating
      modifiers without changing the single-channel conductance. Dose-response analysis
      suggested that two protons are necessary to induce block with an apparent pK of
      approximately 7.1. A simple four-state allosteric model described the modulation
      by Ca(2+) assuming a 13-fold higher Ca(2+) affinity of the open state compared
      with the closed state. The quantitative analysis suggested separate binding sites
      for Ca(2+) and H(+). A mutagenic screen of a large number of extracellularly
      accessible amino acids identified a pair of acidic residues (E261 and D278 on the
      loop connecting helices I and J), which are close to each other but positioned on
      different subunits of the channel, as a likely candidate for forming an
      intersubunit Ca(2+)-binding site. Single mutants E261Q and D278N greatly
      diminished and the double mutant E261Q/D278N completely abolished modulation by
      Ca(2+). Several mutations of a histidine residue (H497) that is homologous to a
      histidine that is responsible for H(+) block in ClC-2 did not yield functional
      channels. However, the triple mutant E261Q/D278N/H497M completely eliminated H(+)
      -induced current block. We have thus identified a protein region that is involved
      in binding these physiologically important ligands and that is likely undergoing
      conformational changes underlying the complex gating of CLC-K channels.

PMID- 20805578
TI  - A mesoscopic approach to understanding the mechanisms underlying the ion
      permeation on the discrete-state diagram.

PMID- 20805577
TI  - Fatty acid modulation and polyamine block of GluK2 kainate receptors analyzed by
      scanning mutagenesis.
AB  - RNA editing of kainate receptor subunits at the Q/R site determines their
      susceptibility to inhibition by cis-unsaturated fatty acids as well as block by
      cytoplasmic polyamines. Channels comprised of unedited (Q) subunits are strongly
      blocked by polyamines, but insensitive to fatty acids, such as arachidonic acid
      (AA) and docosahexaenoic acid (DHA), whereas homomeric edited (R) channels resist
      polyamine block but are inhibited by AA and DHA. In the present study, we have
      analyzed fatty acid modulation of whole-cell currents mediated by homomeric
      recombinant GluK2 (formerly GluR6) channels with individual residues in the pore
      loop, M1 and M3 transmembrane helices replaced by scanning mutagenesis. Our
      results define three abutting surfaces along the M1, M2, and M3 helices where
      gain-of-function substitutions render GluK2(Q) channels susceptible to fatty acid
      inhibition. In addition, we identify four locations in the M3 helix (F611, L614,
      S618, and T621) at the level of the central cavity where Arg substitution
      increases relative permeability to chloride and eliminates polyamine block.
      Remarkably, for two of these positions, L614R and S618R, exposure to fatty acids
      reduces the apparent chloride permeability and potentiates whole-cell currents
      approximately 5 and 2.5-fold, respectively. Together, our results suggest that AA
      and DHA alter the orientation of M3 in the open state, depending on contacts at
      the interface between M1, M2, and M3. Moreover, our results demonstrate the
      importance of side chains within the central cavity in determining ionic
      selectivity and block by cytoplasmic polyamines despite the inverted orientation
      of GluK2 as compared with potassium channels and other pore-loop family members.

PMID- 20805580
TI  - Newer insights into premeiotic development of germ cells in adult human testis
      using Oct-4 as a stem cell marker.
AB  - The transcription factor octamer-binding transforming factor 4 (Oct-4) is central
      to the gene regulatory network responsible for self-renewal, pluripotency, and
      lineage commitment in embryonic stem (ES) cells and induced pluripotent stem
      cells (PSCs). This study was undertaken to evaluate differential localization and
      expression of two major transcripts of Oct-4, viz. Oct-4A and Oct-4B, in adult
      human testis. A novel population of 5- to 10-MUm PSCs with nuclear Oct-4A was
      identified by ISH and immunolocalization studies. Besides Oct-4, other
      pluripotent markers like Nanog and TERT were also detected by RT-PCR. A(dark)
      spermatogonial stem cells (SSCs) were visualized in pairs and chains undergoing
      clonal expansion and stained positive for cytoplasmic Oct-4B. Quantitative PCR
      and Western blotting revealed both the transcripts, with higher expression of Oct
      4B. It is proposed that PSCs undergo asymmetric cell division and give rise to
      A(dark) SSCs, which proliferate and initiate lineage-specific differentiation.
      The darkly stained nuclei in A(dark) SSCs may represent extensive nuclear
      reprogramming by epigenetic changes when a PSC becomes committed. Oct-4B
      eventually disappeared in mature germ cells, viz. spermatocytes, spermatids, and
      sperm. Besides maintaining normal testicular homeostasis, PSCs may also be
      implicated in germ cell tumors and ES-like colonies that have recently been
      derived from adult human testicular tissue.

PMID- 20805581
TI  - Localization of butyrylcholinesterase at the neuromuscular junction of normal and
      acetylcholinesterase knockout mice.
AB  - At the mouse neuromuscular junction (NMJ), there are two distinct cholinesterases
      (ChE): acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Until now,
      it has been difficult to determine the precise localization of BChE at the NMJ.
      In this study, we use a modification of Koelle's method to stain AChE and BChE
      activity. This method does not interfere with fluorescent co-staining, which
      allows precise co-localization of ChE and other synaptic molecules at the NMJ. We
      demonstrate that AChE and BChE exhibit different localization patterns at the
      mouse NMJ. AChE activity is present both in the primary cleft and in the
      secondary folds, whereas BChE activity appears to be almost absent in the primary
      cleft and to be concentrated in subsynaptic folds. The same localization for BChE
      is observed in the AChE-knockout (KO) mouse NMJ. Collagenase treatment removed
      AChE from the primary cleft, but not from secondary folds in the wild-type mouse,
      whereas in the AChE-KO mouse, BChE remains in the secondary folds. After
      peripheral nerve injury and regeneration, BChE localization is not modified in
      either normal or KO mice. In conclusion, specific localization of BChE in the
      secondary folds of the NMJ suggests that this enzyme is not a strict surrogate of
      AChE and that the two enzymes have two different roles.

PMID- 20805582
TI  - Differential endothelial gap junction expression in venous vessels exposed to
      different hemodynamics.
AB  - After being anastomosed with the artery, vein graft is exposed to abruptly
      increased hemodynamic stresses. These hemodynamic stresses may change the profile
      of endothelial gap junction expression as demonstrated in the artery, which may
      subsequently play active roles in physiological adaptation or pathophysiological
      changes of the vein grafts. We investigated the endothelial expression of gap
      junction in the venous vessels exposed to different hemodynamic stresses.
      Immunocytochemical analysis of the endothelial Cx expression was performed by
      observing the whole mounts of inferior vena cava (IVC) of aortocaval fistula
      (ACF) rats or IVC-banded ACF rats using confocal microscope. Immunocytochemical
      analysis demonstrated that in the endothelium of the native vein, the gap
      junctional spot numbers (GJSNs) and the total gap-junctional areas (TGJAs) of
      Cx40 and Cx43 were lower than those of the thoracic aorta and that Cx37 was
      hardly detectable. In the IVCs of ACF rats, which were demonstrated to be exposed
      to a hemodynamic condition of high flow velocity and low pressure, the GJSNs and
      the TGJAs of all three Cxs were increased. In the IVCs of IVC-banded ACF rats,
      which were exposed to a hemodynamic condition of high pressure and low flow
      velocity, the GJSNs and the TGJAs of Cx37 increased markedly and those of Cx40
      and Cx43 remained without significant changes. In conclusion, the endothelial
      expressions of gap junctions in the native veins were lower than those of the
      arteries. When exposed to different hemodynamic stresses, the gap junctions were
      expressed in specific patterns.

PMID- 20805584
TI  - Wuggy: a multilingual pseudoword generator.
AB  - Pseudowords play an important role in psycholinguistic experiments, either
      because they are required for performing tasks, such as lexical decision, or
      because they are the main focus of interest, such as in nonword-reading and nonce
      inflection studies. We present a pseudoword generator that improves on current
      methods. It allows for the generation of written polysyllabic pseudowords that
      obey a given language's phonotactic constraints. Given a word or nonword
      template, the algorithm can quickly generate pseudowords that match the template
      in subsyllabic structure and transition frequencies without having to search
      through a list with all possible candidates. Currently, the program is available
      for Dutch, English, German, French, Spanish, Serbian, and Basque, and, with
      little effort, it can be expanded to other languages.

PMID- 20805583
TI  - Standards for immunohistochemical imaging: a protein reference device for
      biomarker quantitation.
AB  - We are developing a reference device to be used in the validation of
      immunohistochemical imaging of biomarkers by microscopy. The prototype device
      consists of p53 protein immobilized at various concentrations on a glass slide.
      The device is designed as a reference control to be used with assays that
      incorporate commercially available anti-p53 antibodies. p53 protein was
      characterized by mass spectrometry and covalently immobilized through amide
      linkage to the (3-aminopropyl)trietoxysilane-modified glass surface. This
      procedure is reproducible and provides a chemically stable product in high yield.
      The surface-bound protein was shown to be immunoreactive by its specific
      interaction with anti-p53 antibody (Ab) and detection by absorbance and
      fluorescence spectroscopy. Also, comparison was made with microscopic images of
      Ab-stained tissue samples, known to stain positive for p53. Further development
      will be required to establish accurate surface protein concentrations in the
      range required for specific clinical applications.

PMID- 20805585
TI  - Normative multitrial recall performance, metacognitive judgments, and retrieval
      latencies for Lithuanian-English paired associates.
AB  - Memory researchers using paired associates have benefited greatly from the
      Swahili-English norms reported by Nelson and Dunlosky (1994). Given recent
      increases in the amount and kinds of research using paired associates, however,
      researchers would now benefit from an expanded set of normative measures for
      foreign language vocabulary words. We report data for 120 Lithuanian-English word
      pairs collected from 236 undergraduates. Participants completed three study-test
      trials and were asked to make metacognitive judgments for each item. We report
      normative recall performance, recall latencies, and error types for each item
      across trials, as well as the perceived difficulty of each item on the basis of
      metacognitive judgments.

PMID- 20805586
TI  - SUBTLEX-NL: a new measure for Dutch word frequency based on film subtitles.
AB  - We present a new database of Dutch word frequencies based on film and television
      subtitles, and we validate it with a lexical decision study involving 14,000
      monosyllabic and disyllabic Dutch words. The new SUBTLEX frequencies explain up
      to 10% more variance in accuracies and reaction times (RTs) of the lexical
      decision task than the existing CELEX word frequency norms, which are based
      largely on edited texts. As is the case for English, an accessibility measure
      based on contextual diversity explains more of the variance in accuracy and RT
      than does the raw frequency of occurrence counts. The database is freely
      available for research purposes and may be downloaded from the authors'
      university site at http://crr.ugent.be/subtlex-nl or from http://brm.psychonomic
      journals.org/content/supplemental.

PMID- 20805587
TI  - Stimulus design is an obstacle course: 560 matched literal and metaphorical
      sentences for testing neural hypotheses about metaphor.
AB  - Despite the ubiquity and importance of metaphor in thought and communication, its
      neural mediation remains elusive. We suggest that this uncertainty reflects, in
      part, stimuli that have not been designed with recent conceptual frameworks in
      mind or that have been hampered by inadvertent differences between metaphoric and
      literal conditions. In this article, we begin addressing these shortcomings by
      developing a large, flexible, extensively normed, and theoretically motivated set
      of metaphoric and literal sentences. On the basis of the results of three norming
      studies, we provide 280 pairs of closely matched metaphoric and literal sentences
      that are characterized along 10 dimensions: length, frequency, concreteness,
      familiarity, naturalness, imageability, figurativeness, interpretability,
      valence, and valence judgment reaction time. In addition to allowing for control
      of these potentially confounding lexical and sentential factors, these stimuli
      are designed to address questions about the role of novelty, metaphor type, and
      sensory-motor grounding in determining the neural basis of metaphor
      comprehension. Supplemental data for this article may be downloaded from
      http://brm.psychonomic-journals.org/content/supplemental.

PMID- 20805588
TI  - Cloze probability and completion norms for 498 sentences: behavioral and neural
      validation using event-related potentials.
AB  - Three decades after their publication, Bloom and Fischler's (1980) sentence
      completion norms continue to demonstrate widespread utility. The aim of the
      present study was to extend this contribution by expanding the existing database
      of high-constraint, high cloze probability sentences. Using the criteria
      established by Bloom and Fischler, we constructed 398 new sentences and presented
      these along with 100 sentences from their original list to be normed using a
      sample of 400 participants. Of the 498 sentences presented, 400 met criteria for
      high cloze probability-that is, .67 or higher probability of being completed by a
      specific single word. Of these, 321 sentences were from the new set and an
      additional 79 were from Bloom and Fischler's set. A high degree of correspondence
      was observed between responses obtained by Bloom and Fischler for their high
      constraint set. A second experiment utilized an N400 event-related potential
      paradigm to provide further validation of the contextual constraint for the newly
      generated set. As expected, N400 amplitude was greater for sentences that
      violated contextual expectancy by ending in a word other than the newly
      established completion norm. Sentence completion norms are frequently used in
      cognitive research, and this larger database of high cloze probability sentences
      is expected to be of benefit to the research community for many years to come.
      The full set of stimuli and sentence completion norms from this study may be
      downloaded from http://brm.psychonomic-journals.org/content/supplemental.

PMID- 20805589
TI  - Controlling low-level image properties: the SHINE toolbox.
AB  - Visual perception can be influenced by top-down processes related to the
      observer's goals and expectations, as well as by bottom-up processes related to
      low-level stimulus attributes, such as luminance, contrast, and spatial
      frequency. When using different physical stimuli across psychological conditions,
      one faces the problem of disentangling the contributions of low- and high-level
      factors. Here, we make available the SHINE (spectrum, histogram, and intensity
      normalization and equalization) toolbox for MATLAB, which we have found useful
      for controlling a number of image properties separately or simultaneously. The
      toolbox features functions for specifying the (rotational average of the) Fourier
      amplitude spectra, for normalizing and scaling mean luminance and contrast, and
      for exact histogram specification optimized for perceptual visual quality. SHINE
      can thus be employed for parametrically modifying a number of image properties or
      for equating them across stimuli to minimize potential low-level confounds in
      studies on higher level processes.

PMID- 20805590
TI  - A normative set of 98 pairs of nonsensical pictures (droodles).
AB  - Our purpose in the present study is to provide a normative set of nonsensical
      pictures known as droodles and to demonstrate the role of semantic comprehension
      in facilitating recall of pictorial stimuli. The set consists of 98 pairs of
      droodles. Experiment 1 standardized these pictorial stimuli with respect to
      several variables, such as appropriateness of verbal labels, relationship between
      two droodles, and correct recall. Appropriateness of verbal labels was rated
      higher for pictures presented in pairs than for pictures presented singly.
      Experiment 2 used the standardized set of droodles in a recall experiment similar
      to those of Bower, Karlin, and Dueck (1975) and others. As we expected, semantic
      interpretation can strongly facilitate recall. Multiple regression analysis
      showed that several measures had significant power of explanation for recall
      performance. The full set of norms and pictures from this article may be
      downloaded from http://brm.psychonomic-journals.org/content/supplemental.

PMID- 20805591
TI  - ScanMatch: a novel method for comparing fixation sequences.
AB  - We present a novel approach to comparing saccadic eye movement sequences based on
      the Needleman-Wunsch algorithm used in bioinformatics to compare DNA sequences.
      In the proposed method, the saccade sequence is spatially and temporally binned
      and then recoded to create a sequence of letters that retains fixation location,
      time, and order information. The comparison of two letter sequences is made by
      maximizing the similarity score computed from a substitution matrix that provides
      the score for all letter pair substitutions and a penalty gap. The substitution
      matrix provides a meaningful link between each location coded by the individual
      letters. This link could be distance but could also encode any useful dimension,
      including perceptual or semantic space. We show, by using synthetic and
      behavioral data, the benefits of this method over existing methods. The ScanMatch
      toolbox for MATLAB is freely available online (www.scanmatch.co.uk).

PMID- 20805592
TI  - An improved algorithm for automatic detection of saccades in eye movement data
      and for calculating saccade parameters.
AB  - This analysis of time series of eye movements is a saccade-detection algorithm
      that is based on an earlier algorithm. It achieves substantial improvements by
      using an adaptive-threshold model instead of fixed thresholds and using the eye
      movement acceleration signal. This has four advantages: (1) Adaptive thresholds
      are calculated automatically from the preceding acceleration data for detecting
      the beginning of a saccade, and thresholds are modified during the saccade. (2)
      The monotonicity of the position signal during the saccade, together with the
      acceleration with respect to the thresholds, is used to reliably determine the
      end of the saccade. (3) This allows differentiation between saccades following
      the main-sequence and non-main-sequence saccades. (4) Artifacts of various kinds
      can be detected and eliminated. The algorithm is demonstrated by applying it to
      human eye movement data (obtained by EOG) recorded during driving a car. A second
      demonstration of the algorithm detects microsleep episodes in eye movement data.

PMID- 20805593
TI  - A short self-report measure of problems with executive function suitable for
      administration via the Internet.
AB  - This article describes a short self-report measure of problems with executive
      function designed for use in Internet-mediated research. In Study 1, participants
      completed the online measure (Webexec) using a browser but under laboratory
      conditions. They also completed a paper self-report measure of executive problems
      (the Dysexecutive Questionnaire; DEX) and three objective tasks involving
      executive function: reverse digit span, semantic fluency (unconstrained), and
      semantic fluency (constrained). Webexec scores correlated positively with the DEX
      and negatively with the three executive tasks. Further evidence of construct
      validity came from Study 2, in which Webexec scores correlated positively with
      both use of cannabis and prospective memory problems reported in an online drug
      questionnaire. Webexec thus appears suitable for online research with normal
      populations.

PMID- 20805594
TI  - Accuracy and stability of metacognitive monitoring: a new measure.
AB  - An examination of gamma (gamma; Goodman & Kruskal, 1954) and the Hamann
      coefficient (HC; see Schraw, 1995) as a measure of feeling-of-knowing (FOK)
      accuracy in the prediction of subsequent memory performance shows that neither
      coefficient provides a pure measure of accuracy in 2 (feeling-of-not-knowing and
      FOK) x 2 (correct and incorrect recognition) cases. gamma underestimated accuracy
      in the m x 2 case with m being an integer larger than 2, producing low and
      unstable values of gamma. In the present study, FOK predictive accuracy is
      treated as the extent to which the percentage of correct recognition can be
      increased by an increase from one FOK rank to another. A statistic computing the
      relative magnitude of the percentage increase to its maximal increase, designated
      as C, is able to provide a correct estimate of accuracy. Furthermore, the value
      of C is stable across different portions of FOK data and is free from restricted
      /truncated-range and fineness/coarseness effects.

PMID- 20805595
TI  - Self-coded indirect memory associations and alcohol and marijuana use in college
      students.
AB  - Indirect memory associations for substance use predict both the concurrent and
      prospective levels of substance use. These methods assess spontaneous, possibly
      implicit, and easily accessible associations that predict substance use over
      direct (explicit) methods of assessment (e.g., outcome expectancies). The present
      study tested and expanded the application of a coding method for alcohol and
      marijuana associations on the basis of self-coding of indirect responses (Frigon
      & Krank, 2009). College students generated free associates to (1) ambiguous words
      (e.g., draft or weed), (2) situations (e.g., at a party, hanging out with
      friends), and (3) emotions (having fun, feeling dreamy). Later, participants were
      shown their responses and were asked to code their responses according to both
      nonrisk and risk activities, such as alcohol and marijuana use. Self-coded scores
      were higher than researcher-coded scores, captured the same variance, and
      improved the prediction of substance use. Self-coding of indirect memory
      associations provides accurate and efficient prediction of the level of alcohol
      and marijuana. Self-coding is efficient and may be useful for reducing
      ambiguities in coding of many different kinds of open-ended responses.

PMID- 20805596
TI  - PLATT: a flexible platform for experimental research on team performance in
      complex environments.
AB  - The present article introduces PLATT, a recently developed task environment for
      controlled experimental research on team performance in complex environments.
      PLATT was developed to meet the research demands posed by the complexity that
      present-day teams face. It consists of a flexible, modular software architecture
      and research-specific scenarios. The scenarios can target various types of tasks
      (e.g., planning, problem solving, and decision making) in different operational
      contexts. Different software configurations can be used to investigate questions
      pertaining to team structure, team virtuality, and multiteam systems. We describe
      the software architecture, one of the scenarios, and the broad range of automated
      and embedded measurement possibilities that PLATT offers. To illustrate PLATT's
      possibilities, in the present article, we describe a number of experiments that
      have used PLATT for a variety of research questions. We conclude that PLATT meets
      the formulated research demands and provides researchers with a flexible platform
      to investigate the complex issues that present-day teams face.

PMID- 20805597
TI  - Reliability of the 5-min psychomotor vigilance task in a primary school classroom
      setting.
AB  - This study evaluated the reliability of the 5-min psychomotor vigilance task
      (PVT) in a single-sex Australian primary school. Seventy-five male students (mean
      age = 11.82 years, SD = 1.12) completed two 5-min PVTs using a Palm personal
      digital assistant (PDA) in (1) an isolated setting and (2) a classroom setting.
      Of this group of students, a subsample of 37 students completed a test-retest
      reliability trial within the classroom setting. Using a mixed-model analysis,
      there was no significant difference in the mean response time (RT) or number of
      lapses (RTs >or= 500 msec) between the isolated and the classroom setting. There
      was, however, an order effect for the number of lapses in the isolated setting,
      with the number of lapses being greater if the isolated test was conducted
      second. Test-retest intraclass correlation coefficients (ICCs) in the classroom
      setting indicated moderate to high reliability (mean RT = .84, lapses = .59).
      Bland-Altman analysis showed no systematic difference between the two settings.
      Findings suggest that the 5-min PDA PVT is a reliable measure of sustained
      attention in the classroom setting in this sample of primary-aged schoolchildren.
      The results provide further evidence for the versatility of this measuring device
      for larger interventions outside the laboratory.

PMID- 20805598
TI  - Early infant cognitive assessment: validity of an instrument.
AB  - The present study represents a contribution to the assessment of infant cognitive
      development by presenting a valid instrument for observing the development of
      logical reasoning and executive function during the second year of life-key
      processes in the construction of human knowledge. The instrument constructed,
      called ELEDA (Early Logical and Executive Development Assessment), was a combined
      or mixed observation instrument composed of field formats and category systems.
      Its validity was calculated using generalizability theory, which enables
      different sources of error affecting a behavioral measurement to be analyzed
      jointly. The need for valid early cognitive assessment instruments such as the
      one in the present article is evident, since the sooner assessment is performed,
      the sooner action can be taken, thus optimizing the results.

PMID- 20805599
TI  - O-Cam: a new paradigm for investigating the effects of ostracism.
AB  - A new ostracism paradigm-O-Cam-was designed to combine the best qualities of both
      social ostracism (i.e., face-to-face interaction between the target and sources
      of ostracism) and cyber ostracism (i.e., confederate-free, highly controlled
      designs) paradigms. O-Cam consists of a simulated Web conference during which
      participants are either ostracized or included by 2 other participants whose
      actions, unbeknownst to the participants, are actually pretaped. The findings of
      preliminary studies indicate that O-Cam provides a powerful ostracism experience
      that yields psychological and behavioral responses that are consistent with those
      in other ostracism paradigms (e.g., Cyberball; Williams, 2007). Moreover, unlike
      in many previous ostracism paradigms, O-Cam provides researchers with the
      flexibility to manipulate the physical appearance and the verbal/nonbehavior of
      the sources of ostracism without the need for confederates.

PMID- 20805600
TI  - A validation of well-being and happiness surveys for administration via the
      Internet.
AB  - Internet research is appealing because it is a cost- and time-efficient way to
      access a large number of participants; however, the validity of Internet research
      for important subjective well-being (SWB) surveys has not been adequately
      assessed. The goal of the present study was to validate the Satisfaction With
      Life Scale (SWLS; Diener, Emmons, Larsen, & Griffin, 1985), the Positive and
      Negative Affect Schedule (PANAS-X; Watson & Clark, 1994), and the Subjective
      Happiness Scale (SHS; Lyubomirsky & Lepper, 1999) for use on the Internet. This
      study compared the quality of data collected using paper-based (paper-and-pencil
      version in a lab setting), computer-based (Web-based version in a lab setting),
      and Internet (Web-based version on a computer of the participant's choosing)
      surveys for these three measures of SWB. The paper-based and computer-based
      experiment recruited two college student samples; the Internet experiments
      recruited a college student sample and an adult sample responding to ads on
      different social-networking Web sites. This study provides support for the
      reliability, validity, and generalizability of the Internet format of the SWLS,
      PANAS-X, and SHS. Across the three experiments, the results indicate that the
      computer-based and Internet surveys had means, standard deviations,
      reliabilities, and factor structures that were similar to those of the paper
      based versions. The discussion examines the difficulty of higher attrition for
      the Internet version, the need to examine reverse-coded items in the future, and
      the possibility that unhappy individuals are more likely to participate in
      Internet surveys of SWB.

PMID- 20805601
TI  - Development of a new Clarity of Auditory Imagery Scale.
AB  - In the psychological study of auditory imagery, instruments for measuring
      vividness or clarity have existed for some time. The present article argues that
      existing scales are ambiguous, in that clarity and vividness of auditory imagery
      are addressed simultaneously, and that empirical validations of those scales
      suffer from inadequate methods. The aim of the present study was to develop a new
      psychometric scale, the Clarity of Auditory Imagery Scale, measuring individual
      differences in clarity of auditory imagery. Drawing on previous literature, 16
      items were generated, forming an initial item pool that was presented to 212
      respondents. The hypothesized single dimensionality inherent in the data was
      confirmed using Velicer's (1976) minimum average partial test and parallel
      analysis. Also, data were factor analyzed, extracting a stable one-factor
      solution including all 16 items. The internal consistency of the final scale was
      satisfactory (coefficient alpha = .88). Other properties of the questionnaire,
      such as test-retest reliability, remain to be established.

PMID- 20805603
TI  - Structural equation modeling of approval voting data.
AB  - The method of approval voting is a commonly used voting procedure in which each
      judge selects a subset of the alternatives. By postulating that the random
      utilities associated with the choice options in approval voting elections follow
      a multivariate normal distribution under the Thurstonian framework, Regenwetter,
      Ho, and Tsetlin (2007) attempted to integrate the normative theories and
      individual variabilities in modeling social behavior. However, their approach is
      limited to only three alternatives, due to computational intractability as the
      number of alternatives increases. In this article, we reparameterize extensions
      of their models under the structural equation modeling framework and propose the
      use of limited information methods for estimating model parameters. As a result,
      we are able to extend their previous approach to the analysis of approval voting
      data with any number of alternatives. Two applications are presented to
      illustrate the usefulness of such an approach.

PMID- 20805602
TI  - Accuracy of perceptually based and acoustically based inspiratory loci in
      reading.
AB  - Investigations of speech often involve the identification of inspiratory loci in
      continuous recordings of speech. The present study investigates the accuracy of
      perceptually determined and acoustically determined inspiratory loci. While
      wearing a circumferentially vented mask connected to a pneumotach, 16
      participants read two passages. The perceptually determined and acoustically
      determined inspiratory loci were compared with the actual loci of inspiration,
      which were determined aerodynamically. The results showed that (1) agreement
      across all three judges was the most accurate of the approaches considered here
      for detecting inspiratory loci based on listening; (2) the most accurate pause
      duration threshold for detecting inspiratory loci was 250 msec; and (3) the
      perceptually based breath-group determination was more accurate than the
      acoustically based determination of pause duration. Inconsistencies among
      perceptually determined, acoustically determined, and aerodynamically determined
      inspiratory loci are not negligible and, therefore, need to be considered when
      researchers design experiments on breath groups in speech.

PMID- 20805604
TI  - Automatic detection and quantification of growth spurts.
AB  - Growth phenomena are often nonlinear and may contain spurts, characterized by a
      local increase in the rate of growth. Because measurement error and noise may
      produce apparent spurts, it is important to identify systematic and reliable
      spurts. We describe a system, automatic maxima detection (AMD), for statistically
      identifying significant spurts and computing (1) point of maximal velocity, when
      the spurt was most intense; (2) start, when the spurt started; (3) amplitude, the
      intensity of the spurt; and (4) duration, the length of the spurt. We also
      introduce a software implementation of AMD in MATLAB. In growth of height data,
      AMD showed a reliable pubertal growth spurt for most children and a reliable
      prepubertal spurt for some children. In simulated growth of vocabulary, AMD
      showed a large global spurt and several minispurts. In real vocabulary growth,
      AMD showed a few spurts. Advantages of AMD include improvements in objectivity,
      automaticity, quantification, and comprehensiveness.

PMID- 20805605
TI  - Sample size determination for confidence intervals of interaction effects in
      moderated multiple regression with continuous predictor and moderator variables.
AB  - Moderated multiple regression (MMR) has been widely employed to analyze the
      interaction or moderating effects in behavior and related disciplines of social
      science. Much of the methodological literature in the context of MMR concerns
      statistical power and sample size calculations of hypothesis tests for detecting
      moderator variables. Notably, interval estimation is a distinct and more
      informative alternative to significance testing for inference purposes. To
      facilitate the practice of reporting confidence intervals in MMR analyses, the
      present article presents two approaches to sample size determinations for precise
      interval estimation of interaction effects between continuous moderator and
      predictor variables. One approach provides the necessary sample size so that the
      designated interval for the least squares estimator of moderating effects attains
      the specified coverage probability. The other gives the sample size required to
      ensure, with a given tolerance probability, that a confidence interval of
      moderating effects with a desired confidence coefficient will be within a
      specified range. Numerical examples and simulation results are presented to
      illustrate the usefulness and advantages of the proposed methods that account for
      the embedded randomness and distributional characteristic of the moderator and
      predictor variables.

PMID- 20805606
TI  - Parameter identification in multinomial processing tree models.
AB  - Multinomial processing tree models form a popular class of statistical models for
      categorical data that have applications in various areas of psychological
      research. As in all statistical models, establishing which parameters are
      identified is necessary for model inference and selection on the basis of the
      likelihood function, and for the interpretation of the results. The required
      calculations to establish global identification can become intractable in complex
      models. We show how to establish local identification in multinomial processing
      tree models, based on formal methods independently proposed by Catchpole and
      Morgan (1997) and by Bekker, Merckens, and Wansbeek (1994). This approach is
      illustrated with multinomial processing tree models for the source-monitoring
      paradigm in memory research.

PMID- 20805607
TI  - A general framework and an R package for the detection of dichotomous
      differential item functioning.
AB  - Differential item functioning (DIF) is an important issue of interest in
      psychometrics and educational measurement. Several methods have been proposed in
      recent decades for identifying items that function differently between two or
      more groups of examinees. Starting from a framework for classifying DIF detection
      methods and from a comparative overview of the most traditional methods, an R
      package for nine methods, called difR, is presented. The commands and options are
      briefly described, and the package is illustrated through the analysis of a data
      set on verbal aggression.

PMID- 20805608
TI  - Synthesizer 1.0: a varying-coefficient meta-analytic tool.
AB  - Meta-analysis has become an indispensable tool for reaching accurate and
      representative conclusions about phenomena of interest within a research
      literature. However, in order for meta-analytic computations to provide accurate
      estimates of population parameters (e.g., a population correlation), underlying
      statistical models need to be both efficient and unbiased. Current fixed-effect
      (i.e., constant-coefficient) models that assume a common effect for all research
      results perform poorly under conditions of effect size heterogeneity, whereas
      current random-effects (i.e., random-coefficient) models require unrealistic
      assumptions about random sampling of observed effect sizes from a normally
      distributed superpopulation. This article describes a free statistical software
      tool that employs a varying-coefficient model recently proposed by Bonett (2008,
      2009). The software (Synthesizer 1.0) employs procedures that do not require
      effect homogeneity or random sampling of effect sizes from a normal distribution.
      It may be used to meta-analyze correlations, alpha reliabilities, and
      standardized mean differences. The Synthesizer tool for Microsoft Excel 2007 may
      be downloaded from the author at
      www.psychology.iastate.edu/~zkrizan/Synthesizer.htm or as a supplement to the
      article at http://brm.psychonomic-journals.org/content/supplemental.

PMID- 20805609
TI  - Estimating confidence intervals for eigenvalues in exploratory factor analysis.
AB  - Exploratory factor analysis (EFA) has become a common procedure in educational
      and psychological research. In the course of performing an EFA, researchers often
      base the decision of how many factors to retain on the eigenvalues for the
      factors. However, many researchers do not realize that eigenvalues, like all
      sample statistics, are subject to sampling error, which means that confidence
      intervals (CIs) can be estimated for each eigenvalue. In the present article, we
      demonstrate two methods of estimating CIs for eigenvalues: one based on the
      mathematical properties of the central limit theorem, and the other based on
      bootstrapping. References to appropriate SAS and SPSS syntax are included.
      Supplemental materials for this article may be downloaded from
      http://brm.psychonomic-journals.org/content/supplemental.

PMID- 20805610
TI  - SANLab-CM: a tool for incorporating stochastic operations into activity network
      modeling.
AB  - The Stochastic Activity Network Laboratory for Cognitive Modeling (SANLab-CM) is
      a new tool that incorporates stochastic operations into activity network modeling
      (Schweickert, Fisher, & Proctor, 2003). In this article, we discuss the core
      functionality of SANLab-CM and walk through a case study that expands a
      previously published single, static path model of telephone operators interacting
      with customers via a workstation (from Gray, John, & Atwood, 1993) into a
      stochastic model that generates 55 unique paths with different frequencies and a
      variety of qualitative properties. Without SANLab-CM, it would have been easy to
      mistake some of the more frequent critical paths as evidence for alternative
      strategies for task completion. With SANLab-CM, these critical paths can be shown
      to be simple emergent properties of variability in elementary cognitive,
      perceptual, and motor processes.

PMID- 20805611
TI  - Bayesian inference using WBDev: a tutorial for social scientists.
AB  - Over the last decade, the popularity of Bayesian data analysis in the empirical
      sciences has greatly increased. This is partly due to the availability of
      WinBUGS, a free and flexible statistical software package that comes with an
      array of predefined functions and distributions, allowing users to build complex
      models with ease. For many applications in the psychological sciences, however,
      it is highly desirable to be able to define one's own distributions and
      functions. This functionality is available through the WinBUGS Development
      Interface (WBDev). This tutorial illustrates the use of WBDev by means of
      concrete examples, featuring the expectancy-valence model for risky behavior in
      decision making, and the shifted Wald distribution of response times in speeded
      choice.

PMID- 20805612
TI  - Motor vehicle mismatch: a national perspective.
AB  - OBJECTIVE: To determine the RR of the severe injury associated with light truck
      vehicle (LTV) versus passenger vehicle (PV) mismatch following motor vehicle
      collisions across the USA. METHODS: This was a retrospective cohort study with
      the primary outcomes of Injury Severity Score (ISS) >8 and body region
      Abbreviated Injury Score (AIS) >2. The National Automotive Sampling System
      Crashworthiness Data System (NASS CDS) was searched for occupants in frontal and
      side impact crashes from 1993 to 2007. Occupants in PVs struck by LTVs were
      compared to PV occupants struck by another PV. Poisson regression was used to
      estimate the RR of severe injury after adjusting for driver age, driver gender,
      and change in velocity during the crash (Deltav). Because 21% of cases were
      missing Deltav, multiple imputation was used to estimate the missing values. NASS
      CDS weights were used to estimate the risk of severe injury nationally. RESULTS:
      PV occupants in front impact crashes with an LTV as the striking vehicle were at
      increased risk of severe injury compared to those struck by another PV (RR 1.37,
      95% CI 1.09 to 1.73). A similar increase risk was observed in side impact crashes
      (RR 1.34, 95% CI 1.12 to 1.62). Increased risk of injury was also identified in
      several body regions. CONCLUSIONS: Motor vehicle mismatch crashes are associated
      with a significant increase in risk of severe injury for PV occupants in the USA.
      Addressing vehicle compatibility remains an important issue for occupant safety.

PMID- 20805613
TI  - Automated monitoring of clusters of falls associated with severe winter weather
      using the BioSense system.
AB  - OBJECTIVES: To identify and characterise clusters of emergency department (ED)
      visits for fall injuries during the 2007-2008 winter season. METHODS: Hospital ED
      chief complaints and diagnoses from hospitals reporting to the Centers for
      Disease Control and Prevention BioSense system were analysed. The authors
      performed descriptive analyses, used time series charts on data aggregated by
      metropolitan statistical areas (MSAs), and used SaTScan to find spatial-temporal
      clusters of visits from falls. RESULTS: In 2007-2008, 17 clusters of falls in 13
      MSAs were found; the median number of excess ED visits for falls was 71 per day.
      SaTScan identified 11 clusters of falls, of which seven corresponded to MSA
      clusters found by time series and five included more than one state/district.
      Most clusters coincided with known periods of snowfall or freezing rain.
      CONCLUSION: The results show the role that a national automated system can play
      in tracking widespread injuries. Such a system could be harnessed to assist with
      prevention strategies.

PMID- 20805614
TI  - Intentional injuries among Ugandan youth: a trauma registry analysis.
AB  - PURPOSE: To determine intentional injury burden, incident characteristics, and
      outcomes among Ugandan youth. METHODS: A cross sectional analysis of trauma
      registry data from accident and emergency units of five regional referral
      hospitals was conducted. Data had been prospectively collected from all patients
      accessing injury care at the five sites between July 2004 and June 2005: youth
      records were analysed. RESULTS: Intentional injuries among youth victims,
      especially school-age males, are common in all five regions, constituting 7.3% of
      their injury burden with a male dominance. Intentional youth victimisation mainly
      occurred at home, on roads, and in public places; incidents were largely due to
      blunt force, stabs/cuts, and gunshots in general, although variations in causes
      were evident depending on age. Intentional injuries among the youth victims often
      manifested as head, neck, and face injuries: 2% were severe and there were 4%case
      fatalities at 2 weeks. CONCLUSIONS AND RECOMMENDATIONS: Intentional injuries
      among youth victims, especially school-age males, are important contributors of
      injury burden in all five sites. Homes, roads, and public places are unsafe for
      Ugandan youth. Although guns were used in all five sites, less lethal mechanisms
      (blunt force, stabs/cuts, and burns) are the most common with variations between
      locations. Incidents involving teenage housewives could reflect underlying
      problem of domestic violence. Community based studies could be highly
      informative. Youth should be prioritised for prevention of injuries both in and
      out of school.

PMID- 20805615
TI  - Horse-related facial injuries: the perceptions and experiences of riding schools.
AB  - This study aimed to investigate the perceptions and experiences of New Zealand
      horse riding schools with regard to horse-related facial injuries. All the riding
      schools listed in the New Zealand electronic phonebook directory were surveyed by
      post. The survey questions covered riding schools' perceptions of rider profile,
      general and facial injury patterns and safety equipment used. The face was
      perceived to be the most common injury site by only 4% of respondents. Helmets
      were enforced in only 35% of the schools during unmounted activities. Nearly half
      the schools did not enforce any safety equipment for unmounted equestrians. Falls
      were perceived to be the most common cause of facial injury (41%), ahead of horse
      kicks (9%). Poor handling was cited as the most likely cause for horse kick
      related injuries (67%). In summary, riding schools did not perceive the face to
      be among the most common horse-related injury sites. Safety protocols were
      generally directed towards mounted equestrians.

PMID- 20805616
TI  - Associations between adolescent seatbelt non-use, normative perceptions and
      screen media exposure: results from a national US survey.
AB  - BACKGROUND: Failure to use seatbelts in motor vehicles is a major source of youth
      injuries, and previous research has noted the widespread non-use of seatbelts in
      popular media. OBJECTIVES: To explore whether increased exposure to entertainment
      screen media was associated with inflated normative perceptions regarding
      seatbelt non-use, and to determine any associations between normative perceptions
      and seatbelt non-use. METHODS: A nationally representative telephone survey of
      school-aged American adolescents (14-17 years, n=915) measuring: screen media
      exposure; normative perceptions with reference to friends' disapproval of non
      use, and prevalence of non-use among friends, school peers and peers; and self
      reported seatbelt non-use. RESULTS: Using structural equation modelling, analyses
      indicate that, after demographic and individual characteristics relevant to
      screen media exposure and seatbelt non-use had been controlled for, frequent
      exposure to entertainment media was associated with positive normative
      perceptions about seatbelt non-use for boys, but not for girls. Normative
      perceptions related to friends' and school peers' seatbelt use were associated
      with seatbelt non-use for both boys and girls. CONCLUSIONS: Attempts to increase
      adolescent seatbelt use could include public communication campaigns to alter
      normative perceptions. Broadcasting these campaigns in conjunction with the media
      that under-represent seatbelt use may be a successful strategy for reducing the
      influence of such media on male adolescents.

PMID- 20805617
TI  - Injury statistics, high risk groups, and individuals: falling through the cracks.
AB  - The Frank A Calderone Prize in Public Health, the pre-eminent award in the field,
      is overseen by Columbia University's Mailman School of Public Health and
      presented to an individual who has made 'a transformational contribution in the
      field of public health'. The Prize recognises an individual who has accomplished
      extraordinary distinction in public health and/or who has made a specific
      contribution which has had long-term national or global implications. On 6 May
      2010, the prize was awarded to Susan Baker. This is the first time the Prize has
      been bestowed upon an injury control researcher.

PMID- 20805618
TI  - Validation of two child passenger safety questionnaires.
AB  - OBJECTIVE: To measure the validity of a booster seat questionnaire and a car seat
      questionnaire so that they can be reliably used in future trials. DESIGN: The two
      child passenger safety questionnaires were created. Each underwent expert review
      to ensure face and content validity. Two reliability studies were conducted
      independently of each other. Care givers for children who were cared for in a
      paediatric emergency department were enrolled. Criterion validity was tested by
      direct observation, and inter-rater reliability was measured. Test-retest
      reliability and internal consistency were also measured on the booster seat
      questionnaire. RESULTS: Booster seat questionnaire: test-retest agreement was
      good, with 16 of the 18 questions having agreement of at least 80%. Agreement was
      acceptable (>70%) in all other questions in which agreement was expected when the
      answers of two different care givers were compared. All care givers were able to
      report booster seat use as it was found on direct observation, yielding a kappa
      value of 1. Car seat questionnaire: the respondents showed 95% agreement between
      their reported type of child safety restraint and what was found on direct
      observation. Inter-rater agreement for the type of safety restraint was 77% or a
      kappa value of 0.7. CONCLUSION: Both the booster seat questionnaire and the car
      seat questionnaire are valid and can be reliably used in future studies. The
      findings of this study need to be verified with larger studies and different
      populations.

PMID- 20805619
TI  - Determinants of agricultural injury: a novel application of population health
      theory.
AB  - OBJECTIVES: (1) To apply novel population health theory to the modelling of
      injury experiences in one particular research context. (2) To enhance
      understanding of the conditions and practices that lead to farm injury. DESIGN:
      Prospective, cohort study conducted over 2&emsp14;years (2007-09). SETTING: 50
      rural municipalities in the Province of Saskatchewan, Canada. SUBJECTS: 5038
      participants from 2169 Saskatchewan farms, contributing 10,092 person-years of
      follow-up. MAIN MEASURES: Individual exposure: self-reported times involved in
      farm work. Contextual factors: scaled measures describe socioeconomic, physical,
      and cultural farm environments. OUTCOME: time to first self-reported farm injury.
      RESULTS: 450 farm injuries were reported for 370 individuals on 338 farms over 2
      years of follow-up. Times involved in farm work were strongly and consistently
      related to time to first injury event, with strong monotonic increases in risk
      observed between none, part-time, and full-time work hour categories.
      Relationships between farm work hours and time to first injury were not modified
      by the contextual factors. Respondents reporting high versus low levels of
      physical farm hazards at baseline experienced increased risks for farm injury on
      follow-up (HR 1.54; 95% CI 1.16 to 1.47). CONCLUSIONS: Based on study findings,
      firm conclusions cannot be drawn about the application of population health
      theory to the study of farm injury aetiology. Injury prevention efforts should
      continue to focus on: (1) sound occupational health and safety practices
      associated with long work hours; (2) physical risks and hazards on farms.

PMID- 20805621
TI  - Decline in hospitalisations due to dog bite injuries in Catalonia, 1997-2008. An
      effect of government regulation?
AB  - OBJECTIVE: To analyse population-based data on hospitalisation caused by dog bite
      injuries after changes in legal regulations on dog ownership, including breed
      specific regulations. DESIGN: Descriptive study. SETTING: Hospitals in Catalonia
      (Spain), 1997-2008. SUBJECTS: Persons hospitalised with injuries caused by dog
      bites. RESULTS: There has been a significant decline in hospitalisation caused by
      injuries from dog bites from 1.80/100,000 in 1997-9 to 1.11/100,000 in 2006-8,
      after the enactment of stricter regulations on dog ownership in 1999 and 2002.
      The magnitude of this change is significant (-38%), and has been greatest in less
      urban settings. CONCLUSIONS: Government regulations were associated with a
      sizable decrease in injuries caused by dog bites in Catalonia. More evaluative
      studies in this field may provide criteria to focus future regulations and other
      preventive interventions.

PMID- 20805620
TI  - Socioeconomic impact of road traffic injuries in West Africa: exploratory data
      from Nigeria.
AB  - BACKGROUND: Road traffic injuries (RTIs) are increasingly contributing to the
      burden of disease in sub-Saharan Africa, yet little is known about the economic
      consequences and disability associated with them. OBJECTIVE: To explore cost and
      disability consequences of RTIs in Nigeria. DESIGN: A population-based survey
      using two-stage stratified cluster sampling. SUBJECT/SETTING: Information on care
      seeking choice, cost of treatment, ability to work, reduction in earnings, and
      disability were collected on 127 subjects who had suffered an RTI, of 3082 study
      subjects in seven Nigerian states. OUTCOME MEASURES: Univariate analysis was used
      to estimate frequency of disability, types of care sought, and trends for work
      lost, functional ability and cost of treatment. Unadjusted bivariate analysis was
      performed to explore care-seeking, cost of care, and work lost among disabled and
      non-disabled people. RESULTS: RTIs resulted in disability for 29.1% of subjects,
      while 13.5% were unable to return to work. Of the disabled people, 67.6% were
      unable to perform activities of daily living, 16.7% consequently lost their jobs,
      and 88.6% had a reduction in earnings. Private physician and hospital treatment
      were the most common forms of initial treatment sought, but traditional treatment
      was the most common second form of care sought. Average direct costs of informal
      and formal treatment were US$6.65 and US$35.64, respectively. Disabled people
      were more likely to seek formal care (p=0.003) and be unable to work (p=0.002).
      CONCLUSIONS: Economic and functional ramifications must be included in the
      spectrum of consequences of RTIs to fully appreciate the extent of the burden of
      disease, implying that health systems should not only address the clinical
      consequences of RTIs, but the financial ones as well.

PMID- 20805622
TI  - "Please keep an eye on your younger sister": sibling supervision and young
      children's risk of unintentional injury.
AB  - OBJECTIVES: Parental supervision reduces young children's risk of unintentional
      injuries, but supervision by older siblings has been shown to increase risk. The
      current study explored how this differential risk of injury may arise. METHODS:
      The supervision behaviours of mothers were compared to those of their older
      children when each was the designated supervisor of a young child in their family
      in a setting having 'contrived hazards'. RESULTS: Mothers engaged in more
      proactive safety behaviours by removing hazards, whereas older siblings more
      often modelled injury-risk behaviours by interacting with hazards, and
      supervisees were likely to interact with hazards the older sibling touched.
      Supervisees displayed more injury-risk behaviours when supervised by a sibling,
      yet sibling supervisors were less attentive to supervisee risk behaviours than
      mothers. Supervisees also were more non-compliant with older siblings than
      mothers when requested to stop risk taking. CONCLUSIONS: Both supervisor and
      supervisee behaviour patterns contribute to increase the risk of injury when
      older siblings supervise younger ones.

PMID- 20805624
TI  - Comparative determinants of 4-year cardiovascular event rates in stable
      outpatients at risk of or with atherothrombosis.
AB  - CONTEXT: Clinicians and trialists have difficulty with identifying which patients
      are highest risk for cardiovascular events. Prior ischemic events, polyvascular
      disease, and diabetes mellitus have all been identified as predictors of ischemic
      events, but their comparative contributions to future risk remain unclear.
      OBJECTIVE: To categorize the risk of cardiovascular events in stable outpatients
      with various initial manifestations of atherothrombosis using simple clinical
      descriptors. DESIGN, SETTING, AND PATIENTS: Outpatients with coronary artery
      disease, cerebrovascular disease, or peripheral arterial disease or with multiple
      risk factors for atherothrombosis were enrolled in the global Reduction of
      Atherothrombosis for Continued Health (REACH) Registry and were followed up for
      as long as 4 years. Patients from 3647 centers in 29 countries were enrolled
      between 2003 and 2004 and followed up until 2008. Final database lock was in
      April 2009. MAIN OUTCOME MEASURES: Rates of cardiovascular death, myocardial
      infarction, and stroke. RESULTS: A total of 45,227 patients with baseline data
      were included in this 4-year analysis. During the follow-up period, a total of
      5481 patients experienced at least 1 event, including 2315 with cardiovascular
      death, 1228 with myocardial infarction, 1898 with stroke, and 40 with both a
      myocardial infarction and stroke on the same day. Among patients with
      atherothrombosis, those with a prior history of ischemic events at baseline (n =
      21,890) had the highest rate of subsequent ischemic events (18.3%; 95% confidence
      interval [CI], 17.4%-19.1%); patients with stable coronary, cerebrovascular, or
      peripheral artery disease (n = 15,264) had a lower risk (12.2%; 95% CI, 11.4%
      12.9%); and patients without established atherothrombosis but with risk factors
      only (n = 8073) had the lowest risk (9.1%; 95% CI, 8.3%-9.9%) (P < .001 for all
      comparisons). In addition, in multivariable modeling, the presence of diabetes
      (hazard ratio [HR], 1.44; 95% CI, 1.36-1.53; P < .001), an ischemic event in the
      previous year (HR, 1.71; 95% CI, 1.57-1.85; P < .001), and polyvascular disease
      (HR, 1.99; 95% CI, 1.78-2.24; P < .001) each were associated with a significantly
      higher risk of the primary end point. CONCLUSION: Clinical descriptors can assist
      clinicians in identifying high-risk patients within the broad range of risk for
      outpatients with atherothrombosis.

PMID- 20805625
TI  - Multiclass kernel-imbedded Gaussian processes for microarray data analysis.
AB  - Identifying significant differentially expressed genes of a disease can help
      understand the disease at the genomic level. A hierarchical statistical model
      named multiclass kernel-imbedded Gaussian process (mKIGP) is developed under a
      Bayesian framework for a multiclass classification problem using microarray gene
      expression data. Specifically, based on a multinomial probit regression setting,
      an empirically adaptive algorithm with a cascading structure is designed to find
      appropriate featuring kernels, to discover potentially significant genes, and to
      make optimal tumor/cancer class predictions. A Gibbs sampler is adopted as the
      core of the algorithm to perform Bayesian inferences. A prescreening procedure is
      implemented to alleviate the computational complexity. The simulated examples
      show that mKIGP performed very close to the Bayesian bound and outperformed the
      referred state-of-the-art methods in a linear case, a nonlinear case, and a case
      with a mislabeled training sample. Its usability has great promises to problems
      that linear-model-based methods become unsatisfactory. The mKIGP was also applied
      to four published real microarray data sets and it was very effective for
      identifying significant differentially expressed genes and predicting classes in
      all of these data sets.

PMID- 20805626
TI  - Reliability of shoulder internal rotation passive range of motion measurements in
      the supine versus sidelying position.
AB  - STUDY DESIGN: Clinical measurement, reliability. OBJECTIVE: To compare intrarater
      and interrater reliability of shoulder internal rotation (IR) passive range of
      motion measurements utilizing a standard supine position and a sidelying
      position. BACKGROUND: Glenohumeral IR range of motion deficits are often noted in
      patients with shoulder pathology. Excellent intrarater reliability has been found
      when measuring this motion. However, interrater reliability has been reported as
      poor to fair. Some clinicians currently use a sidelying position for IR
      stretching with patients who have shoulder pathology. However, no objective data
      exist for IR passive range of motion measured in this sidelying position, either
      in terms of reliability or normative values. METHODS: Seventy subjects (mean age,
      36.8 years), with (n = 19) and without (n = 51) shoulder pathology, were included
      in this study. Shoulder IR passive range of motion of the dominant shoulder or
      involved shoulder was measured by 2 investigators in 2 positions: (1) a standard
      supine position, with the shoulder at 90 degrees of abduction, and (2) in
      sidelying on the tested side, with the shoulder flexed to 90 degrees . RESULTS:
      Intrarater reliability for supine measurements was good to excellent (ICC3,1 =
      0.70-0.93) and for sidelying measurements was excellent (ICC3,1 = 0.94-0.98).
      Interrater reliability was fair to good for the supine measurement (ICC2,2 = 0.74
      0.81) and good to excellent for the sidelying measurement (ICC2,2 = 0.88-0.96).
      The mean (range) value of the dominant shoulder sidelying IR passive range of
      motion was 40 degrees (11 degrees to 69 degrees ) for healthy subjects and 25
      degrees (-16 degrees to 49 degrees) for subjects with shoulder pathology.
      CONCLUSIONS: For subjects with shoulder pathology, measurements of shoulder IR
      made in the sidelying position had superior intrarater and interrater reliability
      compared to those in the standard supine position.

PMID- 20805627
TI  - Achilles pain, stiffness, and muscle power deficits: achilles tendinitis.

PMID- 20805628
TI  - Foot and ankle pain in a young female athlete.

PMID- 20805629
TI  - Tibial spine avulsion fracture.

PMID- 20805634
TI  - Trajectories of anti-islet autoantibodies before development of type 1 diabetes
      in interferon-treated hepatitis C patients. Case reports and a literature review.
AB  - Interferon-alpha (IFN-alpha) is widely used in the treatment of viral hepatitis,
      however, it is known that IFN-alpha therapy may induce type 1 diabetes. We report
      here on two cases of chronic viral hepatitis C who developed autoimmune type 1
      diabetes during Peg-IFN-alpha plus ribavirin (RBV) therapy. Case 1: a 48-year-old
      male with chronic hepatitis C with chronic thyroiditis. The patient's plasma
      glucose level was normal and anti-islet autoantibody tests were negative before
      Peg-IFN-alpha+RBV therapy. The emergence of glutamic acid decarboxylase 65
      autoantibody (GAD65Ab) was observed after five months of treatment.
      Autoantibodies to insulin and insulinoma-associated antigen-2 (IA-2) also became
      positive. Eleven months later, thirst and polydipsia occurred with increased
      fasting plasma glucose level and the patient was diagnosed with type 1A diabetes.
      Zinc transporter-8 autoantibody (ZnT8Ab) was not detectable at any point. The
      patient has type 1 diabetes-susceptible HLA-DRB1-DQB1 haplotypes *0405-*0401 and
      *0901-*0303. Case 2: a 65-year-old male with chronic hepatitis C with type 2
      diabetes on insulin treatment. GAD65Ab and IA-2Ab were negative before Peg-IFN
      alpha+RBV therapy, however, nine months later, a single appearance of GAD65Ab was
      observed. After twelve months, his plasma glucose control worsened rapidly, and
      he was diagnosed with type 1A diabetes. IA-2Ab and ZnT8Ab were negative
      throughout the clinical course. His HLA-DRB1-DQB1 haplotypes were *0410-*0402 and
      *1407-*0503. Both cases showed a unique GAD65Ab epitope (amino acids 360-442).
      These clinical courses suggest that IFN-alpha therapy provoked acute islet
      autoimmunity and onset of type 1 diabetes. Therefore, during IFN-alpha therapy,
      patients should be closely monitored for the occurrence of type 1 diabetes.

PMID- 20805635
TI  - Alcohol drinking status is associated with serum high molecular weight
      adiponectin in community-dwelling Japanese men.
AB  - AIM: Serum high molecular weight (HMW) adiponectin improves insulin sensitivity,
      and a decreased level of serum HMW adiponectin has been reported as a risk factor
      for the development of diabetes and coronary heart disease. This association may
      be further confounded by the alcohol drinking status, which is involved in the
      development of liver dysfunction. The aim of this study was to determine whether
      the alcohol drinking status is associated with serum HMW adiponectin levels in
      community-dwelling Japanese men. METHODS: A cross-sectional study was carried out
      in 2002. Study participants without a clinical history of diabetes (747 men aged
      60 +/- 14 (mean +/- standard deviation) (range, 20-89) years) were randomly
      recruited from a single community at the time of their annual health examination.
      They were classified into never drinkers, light drinkers (< 1 unit/day), moderate
      drinkers (1-1.9 units/day), and heavy drinkers (>= 2 units/day). We examined the
      effects of alcohol consumption on serum HMW adiponectin. RESULTS: Overall, mean
      serum HMW adiponectin levels were significantly lower in the group with higher
      alcohol consumption, and there were inter-group differences in the alcohol
      drinking status. Moreover, age-adjusted mean serum HMW adiponectin levels were
      significantly lower in the group with higher alcohol consumption. Multiple linear
      regression analysis showed that the alcohol drinking status was significantly and
      independently associated with serum adiponectin as well as age, smoking status,
      TG, HDL-C, LDL-C, serum ALT, and HOMA-IR. Multivariate-adjusted mean serum HMW
      adiponectin levels were also significantly lower in the group with higher alcohol
      consumption. CONCLUSION: The alcohol drinking status is negatively associated
      with serum HMW adiponectin levels in Japanese community-dwelling men.

PMID- 20805636
TI  - Effects of statins on serum inflammatory markers: the U.S. National Health and
      Nutrition Examination Survey 1999-2004.
AB  - AIM: To evaluate the effects of HMG-CoA reductase inhibitor (statin) treatment on
      serum inflammatory markers using data from the National Health and Nutrition
      Examination Survey (NHANES 1999-2004). METHODS AND RESULTS: A total of 9,128
      individuals aged 40 and older participated in the NHANES. The inflammatory
      markers studied were white blood cell counts (WBC), high sensitivity C-reactive
      protein (CRP) and ferritin. Other covariables were: age, gender, race/ethnicity,
      body mass index, prescription or nonprescription medication use within the
      previous 30 days (statins, anti-inflammatory drugs, antibiotics). Four analytic
      groups for drug use were defined: Statin users; AI/Antibiotic users (use of
      either anti-inflammatory or antibiotic drugs); Combination group (use of both
      Statins and anti-inflammatory or antibiotic drugs), and a Non-use group (taking
      none of the listed drugs). The mean CRP level was significantly lower in the
      Statin use group than the Non-use group (0.3 mg/dL, 95%CI: 0.3-0.3 and 0.4 mg/dL,
      95%CI: 0.4-0.5). In multivariable regression modeling, the Statin use group had
      significantly lower predicted mean WBC (Beta Coeff: -0.2, p < 0.05) and CRP (Beta
      Coeff: -0.1, p < 0.01) values than the Non-use group. CONCLUSIONS: Treatment with
      statins was significantly associated with decreased WBC and CRP levels in this
      large population-based sample.

PMID- 20805637
TI  - Effects of supervised aerobic exercise training on serum adiponectin and
      parameters of lipid and glucose metabolism in subjects with moderate
      dyslipidemia.
AB  - AIM: To examine the effects of supervised aerobic exercise training on serum
      adiponectin and lipids, including triglyceride (TG)-rich lipoproteins, in
      moderate dyslipidemic subjects. METHODS: Twenty-five dyslipidemic patients [mean
      body mass index (BMI)=24.6 kg/m2; mean age= 39 years; mean total cholesterol=226
      mg/dL; mean TG=149 mg/dL] without metabolic syndrome, diabetes, and hypertension
      underwent supervised aerobic exercise training (60 min/day, 2 to 3 times/week) at
      an intensity of 60-80% of age-predicted maximal heart rate for 16 weeks.
      Lipoprotein cholesterol levels were measured by our established anion-exchange
      HPLC method. RESULTS: Aerobic exercise training significantly decreased BMI,
      cholesterol levels of LDL- and IDL-, and markedly reduced VLDL-cholesterol at
      week 8 (-45%) and week 16 (-50%), but changes in TG and HDL-cholesterol were not
      significant. Adiponectin significantly increased by 51% and HOMA-R was
      significantly decreased at week 16, although changes in these parameters were not
      significant at week 8. There was no significant relationship between changes in
      adiponectin and in VLDL- or IDL- cholesterol, but changes in adiponectin were
      inversely but insignificantly associated with changes in BMI (r=-0.343, p=0.095).
      CONCLUSIONS: These results suggest that supervised aerobic exercise training two
      to three times/week in the presence of body weight loss increases serum
      adiponectin with an improved lipid profile and insulin sensitivity at week 16 in
      non-obese moderate dyslipidemic patients, and that VLDL-cholesterol is markedly
      decreased by supervised aerobic exercise training.

PMID- 20805638
TI  - Distribution of influenza virus sialoreceptors on upper and lower respiratory
      tract in horses and dogs.
AB  - It is strongly suspected that equine influenza virus (EIV) is the origin of
      canine influenza virus (CIV, H3N8), which was first isolated in U.S.A. in 2004,
      on the basis of phylogenetic analyses. Although the distribution of influenza
      virus sialoreceptors seems to be associated with this interspecies transmission,
      there have been scant data of comparison about distributions of sialoreceptors on
      the whole respiratory tract between horses and dogs. We examined the histological
      distribution of influenza virus sialoreceptors on the upper and lower respiratory
      tract in detail in both animals using double lectin staining with Maackia
      amurensis (specific for SAalpha2,3Gal) and Sambucus sieboldiana (specific for
      SAalpha2,6Gal). SAalpha2,3Gal was observed on the surface of ciliated epithelial
      cells in the nasal mucosa, trachea and bronchus in both animals. The results may
      indicate that dogs are susceptible to EIV without alteration of receptor binding
      specificity.

PMID- 20805639
TI  - Isolation of koala retroviruses from koalas in Japan.
AB  - Koala retrovirus (KoRV) is considered to be associated with leukemia, lymphoma
      and immunodeficiency-like diseases in koalas. We therefore conducted a pilot
      study of KoRV infection in five Queensland koalas in Kobe Municipal Oji Zoo. By
      polymerase chain reaction to detect partial env and pol genes of KoRV in genomic
      DNA isolated from whole blood and feces, all five koalas were found to be
      positive for KoRV proviruses. We succeeded in culturing koala lymphocytes from
      less than 1 ml blood for over 14 days in the presence of recombinant human
      interleukin-2. By coculturing the lymphocytes with human embryonic kidney (HEK)
      293T cells, we isolated KoRVs from all five koalas. We designated these isolates
      as strains OJ-1 to OJ-5. By electron microscopy, we observed C-type retroviral
      particles in HEK 293T cells chronically infected with KoRV strain OJ-4. This is
      the first report on the isolation of KoRV from koalas in a Japanese zoo.

PMID- 20805640
TI  - Examination of the offspring of a Japanese cow affected with L-type bovine
      spongiform encephalopathy.
AB  - The offspring of a beef cow affected with L-type bovine spongiform encephalopathy
      (L-BSE) was kept in a pen at a BSE-dedicated animal facility till the offspring
      was 48 months of age. The steer was then euthanized and subjected to a test for
      BSE. The abnormal isoform of the prion protein was not detected in the brain and
      spinal cord of the steer. Transmission of L-BSE was not observed during 4 years
      of observation, though the steer was born when the dam was in the terminal stages
      of the disease.

PMID- 20805623
TI  - Low-dose vs standard-dose unfractionated heparin for percutaneous coronary
      intervention in acute coronary syndromes treated with fondaparinux: the
      FUTURA/OASIS-8 randomized trial.
AB  - CONTEXT: The optimal unfractionated heparin regimen for percutaneous coronary
      intervention (PCI) in patients with non-ST-segment elevation acute coronary
      syndromes treated with fondaparinux is uncertain. OBJECTIVE: To compare the
      safety of 2 unfractionated heparin regimens during PCI in high-risk patients with
      non-ST-segment elevation acute coronary syndromes initially treated with
      fondaparinux. DESIGN, SETTING, AND PARTICIPANTS: Double-blind randomized parallel
      group trial in 179 hospitals in 18 countries involving 2026 patients undergoing
      PCI within 72 hours, nested within a cohort of 3235 high-risk patients with non
      ST-segment elevation acute coronary syndromes initially treated with fondaparinux
      enrolled from February 2009 to March 2010. INTERVENTIONS: Patients received
      intravenously either low-dose unfractionated heparin, 50 U/kg, regardless of use
      of glycoprotein IIb/IIIa (GpIIb-IIIa) inhibitors or standard-dose unfractionated
      heparin, 85 U/kg (60 U/kg with GpIIb-IIIa inhibitors), adjusted by blinded
      activated clotting time (ACT). MAIN OUTCOME MEASURES: Composite of major
      bleeding, minor bleeding, or major vascular access-site complications up to 48
      hours after PCI. Key secondary outcomes include composite of major bleeding at 48
      hours with death, myocardial infarction, or target vessel revascularization
      within day 30. RESULTS: The primary outcome occurred in 4.7% of those in the low
      dose group vs 5.8% in the standard-dose group (odds ratio [OR], 0.80; 95%
      confidence interval [CI], 0.54-1.19; P = .27). The rates of major bleeding were
      not different but the rates of minor bleeding were lower with 0.7% in the low
      dose group vs 1.7% in the standard-dose group (OR, 0.40; 95% CI, 0.16-0.97; P =
      .04). For the key secondary outcome, the rates for low-dose group were 5.8% vs
      3.9% in the standard-dose group (OR, 1.51; 95% CI, 1.00-2.28; P = .05) and for
      death, myocardial infarction, or target vessel revascularization it was 4.5% for
      the low-dose group vs 2.9% for the standard-dose group (OR, 1.58; 95% CI, 0.98
      2.53; P = .06). Catheter thrombus rates were very low (0.5% in the low-dose group
      and 0.1% in the standard-dose group, P = .15). CONCLUSION: Low-dose compared with
      standard-dose unfractionated heparin did not reduce major peri-PCI bleeding and
      vascular access-site complications. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00790907.

PMID- 20805641
TI  - Decreasing expression of the interleukin-13 receptor IL-13Ralpha2 in treated
      recurrent malignant gliomas.
AB  - The IL-13Ralpha2 gene encodes for a 65 kDa protein that forms one of the subunits
      of the interleukin-13 (IL-13) receptor. This gene is highly expressed in various
      types of human tumors including malignant gliomas. The expression level of IL
      13Ralpha2 was examined in a total of 45 tissue samples of anaplastic astrocytomas
      (AAs) World Health Organization (WHO) grade III, glioblastomas (GBMs) WHO grade
      IV, and first-recurrent glioblastomas (frGBMs) after treatment with radiation and
      chemotherapy. IL-13Ralpha2 expression was detected by semiquantitative reverse
      transcription real-time polymerase chain reaction (PCR) using ABI PRISM 7700 and
      Qiagen QuantiTect SYBR Green PCR kits. The expression level of IL-13Ralpha2 (15
      fold) was significantly reduced in frGBMs compared to the primary GBMs (p =
      0.014), and significantly reduced by more than 15 fold (p = 0.003) in all
      untreated malignant astrocytomas (AAs and GBMs) compared with treated frGBMs.
      Expression of IL-13Ralpha2 seems to be lower in frGBMs compared to GBMs. The
      promising antitumor effect of IL-13 cytotoxin could be greatly reduced in frGBM
      or only achievable with higher amounts of cytotoxin, due to the significantly
      lower expression of the cytotoxin's target structure.

PMID- 20805642
TI  - Intravenous methylprednisolone reduces the risk of propofol-induced adverse
      effects during Wada testing.
AB  - The adverse effects and risks associated with intracarotid propofol injection
      during Wada testing were retrospectively compared in two groups of patients with
      (n = 75) and without (n = 58) intravenous methylprednisolone administered before
      intracarotid propofol injection. The incidences of all adverse effects were
      decreased in the methylprednisolone group. In particular, severe adverse effects
      such as increased muscle tone with twitching and rhythmic movements or tonic
      posture, which could adversely affect Wada test results, were seen in one patient
      in the methylprednisolone group and seven patients in the control group,
      indicating 92% risk reduction. This study suggests that Wada testing using
      intravenous methylprednisolone administration prior to propofol injection is a
      safe approach to the preoperative evaluation of brain tumors, epilepsy, and
      arteriovenous malformations.

PMID- 20805643
TI  - Novel brain model for training of deep microvascular anastomosis.
AB  - Models of the brain and skull were developed using a selective laser sintering
      method for training in the procedures of deep microvascular anastomosis. Model A
      has an artificial skull with two craniotomies, providing fronto-temporal
      subtemporal and suboccipital windows. The brain in Model A is soft and elastic,
      and consists of the brainstem and a hemispheric part with a detailed surface.
      Rehearsals or training for anastomosis to the insular part of the middle cerebral
      artery, superior cerebellar artery, posterior cerebral artery, and posterior
      inferior cerebellar artery can be performed through the craniotomies. Model B has
      an artificial skull with a bifrontal craniotomy and an artificial brain
      consisting of the bilateral frontal lobes with an interhemispheric fissure and
      corpus callosum. Rehearsals or training for anastomosis of the callosal segment
      of the anterior cerebral artery can be practiced through this craniotomy. These
      realistic models will help to develop skills for deep vascular anastomosis, which
      remains a challenging neurosurgical procedure, even for experienced
      neurosurgeons.

PMID- 20805644
TI  - Benefits of clipping surgery based on three-dimensional computed tomography
      angiography.
AB  - The recent development of three-dimensional computed tomography (3D-CT)
      angiography with multi detector row CT (MDCT) improves cerebral artery imaging
      due to faster scanning at thinner collimation over a large scanning volume.
      Aneurysm clipping was performed using only 3D-CT angiography created by MDCT with
      16 detector arrays (16-MDCT angiography), in place of digital subtraction
      angiography (DSA) to evaluate the suitability of 16-MDCT angiography for
      preoperative examination before aneurysm clipping, and identify the essential
      points when making 3D images. Thirty-two patients with subarachnoid hemorrhage
      (SAH) identified by initial CT or with non-ruptured aneurysm were entered in this
      study. Twenty-six SAH patients underwent 3D-CT angiography, and aneurysms were
      treated by clipping (n = 25) or coil embolization (n = 4). One patient with no
      aneurysm depicted by 3D-CT angiography underwent conventional DSA twice
      subsequently. The sensitivity of 16-MDCT angiography to depict aneurysms in
      patients with SAH, and time between admission and entering the operating room
      were evaluated, and compared with those under the former protocol using DSA. The
      sensitivity of 16-MDCT angiography for aneurysm detection was 100%. Shapes of all
      aneurysms depicted by 3D-CT angiography were validated intra-operatively. The
      mean operation waiting time was 2.8 hours, with the shortest time being 1.5
      hours. Re-bleeding occurred in one of the 20 patients. We conclude that shorter
      preoperative waiting time decreased the incidence of premature re-bleeding,
      resulting in better outcomes. We highly recommend that the surgeon sets the
      threshold value, and rotates the 3D image to establish better surgical
      orientation.

PMID- 20805645
TI  - Low peripheral lymphocyte count before focal radiotherapy plus concomitant
      temozolomide predicts severe lymphopenia during malignant glioma treatment.
AB  - Malignant glioma patients treated with the golden standard therapy, focal
      radiotherapy plus concomitant daily temozolomide (radiotherapy/TMZ), often suffer
      severe lymphopenia. The frequency of severe lymphopenia and its predictors were
      analyzed by assessing adverse effects including decrease in white blood cell
      counts, lymphocyte counts, and neutrocyte counts according to the Common Toxicity
      Criteria version 3.0 (CTC) in 28 consecutive patients with pathologically
      verified malignant gliomas treated with radiotherapy/TMZ. Eighty-two percent of
      the patients suffered one or more adverse effects; lymphopenia (68%) was the most
      frequent adverse effect, with 32% of patients suffering CTC grade 4 lymphopenia.
      CTC grade 4 lymphopenia was associated with the incidence of other CTC grade 3 or
      4 adverse effects and discontinuance of TMZ. Minimal lymphocyte counts during
      radiotherapy/TMZ and lymphocyte counts before radiotherapy/TMZ showed close
      linear correlation by linear regression analysis (p < 0.0001, R(2) = 0.569), and
      the most important predictor for CTC grade 4 lymphopenia was lymphocyte count
      before radiotherapy/TMZ less than 1200/microl by multivariate analysis (p <
      0.0321, Exp = 13.2). Lymphocyte counts before radiotherapy/TMZ of less than
      1200/microl predict severe lymphopenia during radiotherapy/TMZ.

PMID- 20805646
TI  - Two-level anterior lumbar interbody fusion with percutaneous pedicle screw
      fixation: a minimum 3-year follow-up study.
AB  - The clinical and radiological outcomes of two-level anterior lumbar interbody
      fusion (ALIF) with percutaneous pedicle screw fixation (PSF) were evaluated in 24
      consecutive patients who underwent two-level ALIF with percutaneous PSF for
      segmental instability and were followed up for more than 3 years. Clinical
      outcomes were assessed using a visual analogue scale (VAS) score and the Oswestry
      Disability Index (ODI). Sagittal alignment, bone union, and adjacent segment
      degeneration (ASD) were assessed using radiography and magnetic resonance
      imaging. The mean age of the patients at the time of operation was 56.3 years
      (range 39-70 years). Minor complications occurred in 2 patients in the
      perioperative period. At a mean follow-up duration of 39.4 months (range 36-42
      months), VAS scores for back pain and leg pain, and ODI score decreased
      significantly (from 6.5, 6.8, and 46.9% to 3.0, 1.9, and 16.3%, respectively).
      Clinical success was achieved in 22 of the 24 patients. The mean segmental
      lordosis, whole lumbar lordosis, and sacral tilt significantly increased after
      surgery (from 25.1 degrees , 39.2 degrees , and 32.6 degrees to 32.9 degrees ,
      44.5 degrees , and 36.6 degrees , respectively). Solid fusion was achieved in 21
      patients. ASD was found in 8 of the 24 patients. No patient underwent revision
      surgery due to nonunion or ASD. Two-level ALIF with percutaneous PSF yielded
      satisfactory clinical and radiological outcomes and could be a useful alternative
      to posterior fusion surgery.

PMID- 20805647
TI  - Reversible magnetic resonance imaging changes associated with hypoglycemia. Case
      report.
AB  - A 63-year-old man was found with confusion and right limb monoparesis. He was
      taken to the emergency center under suspicion of stroke. Head computed tomography
      and magnetic resonance (MR) imaging and MR angiography were immediately
      conducted, which revealed no abnormality, but diffusion-weighted imaging showed
      increased intensity areas in the splenium of the corpus callosum and the left
      posterior limb of the internal capsule with decreased apparent diffusion
      coefficient (ADC) in the same areas. Immediately after the head scan, blood sugar
      level was measured, which revealed hypoglycemia (23 mg/dl). He quickly became
      lucid after intravenous administration of 20 ml of 50% glucose solution, and the
      paresis disappeared. Follow-up brain MR imaging was conducted 3 days later, but
      no clearly abnormal findings were seen on T(2)-weighted, fluid-attenuated
      inversion recovery, diffusion-weighted, or ADC images. Reports of reversible high
      intensity area in the splenium of the corpus callosum on diffusion-weighted
      imaging due to transient hypoglycemia are rare. Hemiparesis is one of the
      manifestations of hypoglycemia, so verifying the blood sugar level is important.
      Since MR imaging can be conducted easily now, we may need to consider the imaging
      findings in the differential diagnosis of hypoglycemia.

PMID- 20805648
TI  - Vertebral artery dissecting aneurysm treated by proximal occlusion and posterior
      inferior cerebellar artery reconstruction with fenestrated clips. Case report.
AB  - A 57-year-old man presented with subarachnoid hemorrhage caused by a dissecting
      aneurysm of the vertebral artery close to the origin of the posterior inferior
      cerebellar artery (PICA). The aneurysm was treated successfully with two
      fenestrated clips preserving the efferent artery with anterograde blood flow
      without PICA anastomosis. The postoperative course was uneventful. Postoperative
      angiography indicated disappearance of the aneurysm and anterograde blood flow of
      the PICA.

PMID- 20805649
TI  - Recurrence of subarachnoid hemorrhage due to the rupture of cerebral aneurysms in
      a patient with Sjogren's syndrome. Case report.
AB  - A 52-year-old woman with Sjogren's syndrome presented with multiple cerebral
      aneurysms, which resulted in recurrent subarachnoid hemorrhage (SAH) manifesting
      as severe headache. Computed tomography (CT) showed SAH. Cerebral angiography
      revealed aneurysms of the anterior communicating artery and the left middle
      cerebral artery. The necks of the aneurysms were successfully clipped.
      Postoperative course was uneventful and she was discharged without neurological
      deficit. Thirteen years later, she suddenly lost consciousness and was brought to
      our hospital. CT demonstrated recurrence of SAH. Cerebral angiography revealed
      cerebral aneurysms of the right internal carotid artery and the right middle
      cerebral artery. The clipped aneurysms were stable. The internal carotid artery
      aneurysm was successfully treated with endovascular coil embolization. However,
      she regained no neurological function and died. Patients with Sjogren's syndrome
      may develop cerebral aneurysm complicated with SAH.

PMID- 20805650
TI  - Delayed parenchymal hemorrhage following successful embolization of brainstem
      arteriovenous malformation. Case report.
AB  - A 64-year-old man presented with subarachnoid hemorrhage from a small brainstem
      arteriovenous malformation (AVM). Cerebral angiography showed a small AVM in the
      lateral midbrain, which was fed by a basilar perforating artery, and drained into
      the right transverse pontine vein and superior petrous vein. Endovascular
      embolization in the acute stage was selected to occlude the arteriovenous shunt
      and provide additional intensive treatment for cerebral spasm with lower risk of
      rebleeding. The AVM was occluded by embolization using n-butyl cyanoacrylate.
      Intraparenchymal hemorrhage in the ipsilateral pons was detected 1 month after
      treatment. The causes of the hemorrhage remain unclear.

PMID- 20805651
TI  - Cushing's disease associated with unruptured large internal carotid artery
      aneurysm. Case report.
AB  - A 40-year-old woman with Cushing's disease presented with hypertensive cerebral
      hemorrhage. Neuroimaging detected an unruptured large intracavernous aneurysm,
      which projected beyond the midline, and thin crescent-shaped adenoma along the
      aneurysm wall. The aneurysm was treated with endovascular tight packing with
      coils. Transsphenoidal adenomectomy was then safely performed. The signs of
      Cushing's disease were resolved, and she was discharged without deficits. The
      first line therapy for Cushing's disease is transsphenoidal adenomectomy.
      However, the therapeutic strategy and optimal timing of treatment are unclear for
      Cushing's disease with large intracavernous aneurysm. The present case shows that
      transsphenoidal surgery was safely possible with minimal invasiveness after
      embolization of the intracavernous aneurysm.

PMID- 20805652
TI  - Familial moyamoya disease associated with Graves' disease in a mother and
      daughter. Two case reports.
AB  - A mother and daughter presented with a rare combination of moyamoya disease and
      Graves' disease. A 19-year-old woman experienced numbness in her right hand due
      to cerebral infarction during therapy for Graves' disease. Cerebral angiography
      demonstrated stenoses of the bilateral internal carotid arteries and net-like
      abnormal collateral vessels indicative of moyamoya disease. Her 52-year-old
      mother with a history of Graves' disease presented with left hemiparesis due to
      intracerebral hemorrhage; she recovered after hematoma evacuation. Postoperative
      angiography demonstrated stenoses of the bilateral internal carotid arteries and
      net-like abnormal collateral vessels indicative of moyamoya disease. Another
      otherwise healthy daughter manifested slight stenosis of the left internal
      carotid artery. After cerebral revascularization surgery the patients were able
      to return to their normal daily lives. These familial cases of moyamoya disease
      and Graves' disease indicate hereditary involvement in both diseases.

PMID- 20805653
TI  - Symptomatic T2 vertebral hemangioma in a pregnant woman treated by one stage
      combination surgery; posterior stabilization and anterior subtotal tumor
      resection. Case report.
AB  - A 27-year-old woman presented with vertebral hemangioma manifesting as sudden
      onset of paraplegia, and bladder and bowel dysfunction during pregnancy. Magnetic
      resonance imaging revealed a mass lesion that had infiltrated into the entire T2
      vertebral body and expanded to the vertebral canal. Laminectomy from T1 to T3 and
      biopsy of the lesion were performed. Biopsy confirmed the diagnosis of vertebral
      hemangioma, but laminectomy resulted in no neurological changes. The patient was
      transferred to our hospital, where radical treatment comprising embolization of
      the feeding arteries, posterior stabilization of the vertebrae, and anterior
      excision of the tumor was performed. Symptoms resolved gradually but steadily,
      and she made a full recovery by 18 months postoperatively. Radical operation
      might be extremely effective for extradural vertebral hemangioma, even in the
      delayed phase or in the presence of severe neurological deficit.

PMID- 20805654
TI  - Infantile cervical intramedullary cavernous angioma manifesting as hematomyelia.
      Case report.
AB  - A 2-month-old infant presented with a cervical intramedullary spinal cord
      cavernous angioma manifesting as left hemiparesis caused by hematomyelia.
      Osteoplastic laminotomy of the cervical spine was carried out with subsequent
      microsurgical excision of the intramedullary spinal cord cavernous angioma.
      Magnetic resonance imaging revealed no residual tumor. At 25 months after the
      surgery, she presented no neurological deficit without recurrence and cervical
      deformity. This case of infantile intramedullary spinal cord cavernous angioma
      presenting with cervical hematomyelia shows osteoplastic laminotomy of the
      cervical spine might be helpful to prevent consequent cervical deformity in
      pediatric cases.

PMID- 20805655
TI  - Solitary intraosseous neurofibroma of the frontal bone. Case report.
AB  - A 54-year-old female presented with a very rare intraosseous neurofibroma of the
      frontal bone manifesting as forehead bulging. Skull radiography showed a
      radiolucent round lesion. Magnetic resonance imaging showed a mass lesion
      expanding from the frontal bone diploic layer to the epidural space.
      Fluorodeoxyglucose positron emission tomography and thallium-201 single photon
      emission computed tomography findings indicated tumor malignancy. The tumor was
      resected, and the histological diagnosis was benign intraosseous neurofibroma.
      Intraosseous neurofibroma usually occurs in the mandible. The origin of the
      present case may have been a peripheral nerve in the diploic vascular tissue.

PMID- 20805656
TI  - Two meningiomas with different histological grades in the same patient. Case
      report.
AB  - A 56-year-old female presented with two intracranial meningiomas with different
      grades manifesting as speech disorder for one week. Neurological and radiological
      evaluations showed two distinct tumors suggestive of multicentric meningiomas.
      Surgical resection of both masses was performed in the same procedure.
      Histological examination found both meningothelial and atypical meningiomas.
      Concurrency of meningiomas with different grades in same patient is extremely
      rare. The present case emphasizes the need for follow up of all patients with
      meningioma even if the neuroimaging features indicate benign character.

PMID- 20805657
TI  - Brain metastasis of undifferentiated sarcoma and response to temozolomide
      treatment. Case report.
AB  - A 33-year-old woman presented with rare brain metastases from undifferentiated
      high-grade sarcoma manifesting as headache and vomiting. Magnetic resonance (MR)
      imaging demonstrated multiple tumors in the brain, subcutaneous soft tissue, and
      mediastinum. The patient underwent surgery, followed by chemotherapy and
      radiotherapy. The histological diagnosis was undifferentiated high-grade sarcoma.
      Radiotherapy was effective, but the brain tumors recurred 6 months later. The
      patient underwent high-dose methotrexate therapy, but showed no response.
      Promoter hypermethylation in the O(6)-methylguanine-deoxyribonucleic acid
      methyltransferase (MGMT) genes was detected and MGMT protein expression was
      negative in the recurrent tumor, so temozolomide (TMZ) salvage chemotherapy was
      given, and follow-up MR imaging showed tumor reduction. This case suggests that
      TMZ may be effective for brain metastasis of undifferentiated sarcoma without
      MGMT protein expression.

PMID- 20805659
TI  - Arachnoidplasty for traumatic subdural hygroma associated with arachnoid cyst in
      the middle fossa. Case report.
AB  - A 5-year old boy presented with an arachnoid cyst in the middle cranial fossa
      with mild midline shift manifesting as headache and loss of activity. Computed
      tomography (CT) showed subdural hygroma. Burr-hole drainage was carried out and
      symptoms were improved postoperatively. However, recollection of subdural hygroma
      was found on follow-up CT 3 weeks after subdural drainage. He underwent
      craniotomy, and tearing of the outer wall of the arachnoid cyst was observed. The
      ruptured cyst wall was tightly closed by arachnoidplasty to prevent cerebrospinal
      fluid leakage. Arachnoidplasty was effective for traumatic subdural hygroma with
      arachnoid cyst for reconstruction.

PMID- 20805658
TI  - Langerhans cell histiocytosis of the petrous bone with sudden sensorineural
      hearing loss. Case report.
AB  - A 56-year-old woman with Langerhans cell histiocytosis of the petrous bone
      presented with sudden onset of sensorineural hearing loss and vertigo without
      other neurological impairment, mimicking idiopathic sudden sensorineural hearing
      loss. Differential diagnosis was difficult until neuroimaging demonstrated a
      lesion of the petrous bone. The patient eventually underwent removal of the
      lesion via the transpetrosal approach, and received postoperative chemotherapy
      consisting of vinblastine, methotrexate, 6-mercaptopurine, and prednisolone.
      Although her hearing did not recover, complete remission was achieved, and the
      patient is currently free from disease. Physicians need to be aware that patients
      with sudden onset of hearing loss may have an unexpected and hidden disease which
      requires neuroimaging and histological examinations for definitive diagnosis and
      appropriate treatment.

PMID- 20805660
TI  - Epidermoid cyst in Meckel's cave with unusual computed tomography and magnetic
      resonance imaging findings. Case report.
AB  - A 27-year-old woman presented with headache and occasional numbness over her
      right face. Computed tomography revealed a hypodense mass in the middle cranial
      fossa and another adjacent hyperdense mass in the posterior fossa with erosion of
      the right petrous apex. Magnetic resonance imaging revealed the lesion in the
      middle cranial fossa as iso- to hypointense on T(1)-weighted and hyperintense on
      T(2)-weighted imaging, with peripheral enhancement after gadolinium
      administration, and the adjacent lesion in the posterior fossa as hyperintense on
      T(1)-weighted and hypointense on T(2)-weighted imaging. During surgery, these
      lesions mimicking two adjacent distinct tumors were revealed to connect through
      Meckel's cave. The hypodense lesion in the middle cranial fossa consisted of
      pearly-like solid contents, and the hyperdense lesion in the posterior cranial
      fossa consisted of viscid dark-green materials. The tumors were gross totally
      resected with endoscopic assistance. Histological examination confirmed that the
      tumor was an epidermoid cyst. The present case cyst indicates that although the
      diffusion-weighted imaging sequence is useful for detection of intracranial
      epidermoid cysts, epidermoid cysts including viscous materials with unusual
      radiological findings could complicate the preoperative diagnosis.

PMID- 20805661
TI  - Supplementary comment on "Neuropsychological improvement in patients with
      cervical spondylotic myelopathy after posterior decompression surgery".

PMID- 20805662
TI  - [Picture in clinical hematology no.47: Case with lymphatic metastasis of
      malignant melanoma].

PMID- 20805663
TI  - [Pathophysiology and treatment of large granular lymphocyte leukemia-associated
      pure red cell aplasia].

PMID- 20805664
TI  - [Development of ABL tyrosine kinase inhibitors].

PMID- 20805665
TI  - [Function of role of polycomb group complexes and possibility of novel molecular
      target in cancer].

PMID- 20805666
TI  - [Important role of fibrinogen beyond hemostasis].

PMID- 20805667
TI  - [Pathogenesis of chronic inflammation revealed by in vivo imaging: thrombus
      formation and platelet function].

PMID- 20805668
TI  - [Development of platelet-directed gene modification by lentiviral vector].

PMID- 20805669
TI  - [Visualization of cancer stem cells and their vascular niche].

PMID- 20805670
TI  - [Impaired ribosomal protein and bone marrow failure].

PMID- 20805671
TI  - [Bone marrow failure due to telomere associated gene mutation].

PMID- 20805672
TI  - [Diagnosis of immunopathophysiology in bone marrow failure: clinical significance
      of autoantibody detection].

PMID- 20805673
TI  - [Molecular pathogenesis of bone marrow failure in paroxysmal nocturnal
      hemoglobinuria: a role of NKG2D-medicated immunity].

PMID- 20805674
TI  - [Development of cancer stem cell research in gastrointestinal tumors].

PMID- 20805675
TI  - [Hematopoietic stem cells are primarily involved in pathogenesis of chronic
      lymphocytic leukemia].

PMID- 20805676
TI  - [Prediction of treatment efficacy by the M-protein reduction rate after the first
      cycle of VAD therapy for multiple myeloma].
AB  - In recent years, novel drugs for multiple myeloma such as bortezomib and
      thalidomide have been shown to be effective. However, in Japan, these drugs are
      indicated only for patients with relapsed or refractory multiple myeloma. There
      are no established criteria for the definition of refractory cases, and it is
      often difficult to determine when treatment methods should be changed for those
      cases. Therefore, we performed a retrospective study to investigate whether
      treatment responses can be predicted in the early stage of VAD therapy. After the
      first and third cycles of VAD, the M-protein reduction rate was evaluated. As a
      result, it was estimated with a 50% probability that an M-protein reduction rate
      of 87.6% (lower limit of the 95% CI, 73.9%) after the first cycle of VAD can
      predict a reduction of 90% after the third cycle. The progression-free survival
      period was slightly longer in the group achieving 90% M-protein reduction after
      the third cycle than in the group who did not achieve this rate (3.3 vs 2.2
      years, p=0.09). These findings suggest that a change from conventional to novel
      therapeutic drugs in refractory cases identified by the responses to the first
      cycle of VAD can be a beneficial treatment strategy.

PMID- 20805677
TI  - [Multiple myeloma complicated with disseminated zygomycosis after bortezomib
      therapy].
AB  - A 67-year-old man was diagnosed with multiple myeloma IgA-lambda type, Durie
      Salmon classification stage IIIA in October 2001. He received five courses of
      induction chemotherapy consisting of vincristine, doxorubicin and dexamethasone
      and then underwent high dose chemotherapy followed by autologous stem cell
      transplantation in March 2003. He achieved partial response, but then relapsed
      after treatment with thalidomide and was admitted to our hospital in June 2007.
      The patient was complicated by tumor lysis syndrome (TLS) after receiving
      bortezomib therapy twice. Computed tomography after bortezomib therapy showed the
      rapid appearance of tumors in the right upper lobe of the lung, tail of the
      pancreas and the spleen. Though he was treated with antifungal agents, micafungin
      and voriconazole, he died eighty-five days after admission. Autopsy specimen
      showed fungal clumps and hemorrhagic infarction in the lung and spleen, and
      vegetation at the mitral valve was the same fungus as found in the lung. We
      diagnosed disseminated zygomycosis based on the pathological fungal morphology.
      This case suggested that metabolic acidosis was caused by TLS, while poorly
      controlled diabetes, secondary hemochromatosis due to transfusion, and
      breakthrough zygomycosis during antifungal therapy were thought to be factors
      contributing to the development of zygomycosis.

PMID- 20805678
TI  - Prevalence, classification, and etiology of pain in Parkinson's disease:
      association between Parkinson's disease and fibromyalgia or chronic widespread
      pain.
AB  - Parkinson's disease (PD) is characterized by resting tremor, slow and decreased
      movement (hypokinesia and akinesia), rigidity, postural instability, problems
      with gait, and coordination. The prevalence of PD is between 0.1% and 0.3% in the
      general population and between 1% and 2% in persons 65 years of age or older.
      Patients with PD are more likely to suffer from pain. Indeed, the chief complaint
      of patients with severe motor disturbance and severe pain is pain rather than
      motor disturbance. Fibromyalgia (FM) is defined by widespread pain (pain in the
      left and right sides of the body, pain above the waist, pain below the waist, and
      axial skeletal pain) for more than 3 months and the presence of at least 11 of
      the 18 specified tender points. FM and chronic widespread pain (CWP), which is
      usually an incomplete form of FM, cause pain in the musculoskeletal region, but
      their etiologies are unknown. Therefore, it is almost impossible to determine
      whether or not pain in the musculoskeletal region is in the musculoskeletal
      origin. We suspect that dysfunction or degeneration of the nerves that control
      pain, mind, and movement in the brain causes FM, depression, and PD,
      respectively. When pain in PD is discussed, FM and CWP should be considered
      because their prevalence is high. Patients with PD may be likely to suffer from
      FM and CWP; however, the prevalence of FM and CWP in patients with PD has not
      been reported. Here, we discuss the relationship between PD and FM or CWP.

PMID- 20805679
TI  - Growth hormone releasing peptide-2, a ghrelin agonist, attenuates
      lipopolysaccharide-induced acute lung injury in rats.
AB  - Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome
      (ARDS), are the most common complications of sepsis, and the mortality of sepsis
      induced ALI remains high in critically ill patients. Growth hormone releasing
      peptide-2 (GHRP-2), a ghrelin agonist, has been shown to exert beneficial effects
      on various inflammatory diseases. We therefore explored whether GHRP-2 possesses
      anti-inflammatory properties in the pathogenesis of lipopolysaccharide (LPS)
      induced ALI. Male Sprague-Dawley rats were intratracheally instilled with LPS (2
      mg/kg) to induce ALI. ALI was confirmed with lung tissue injury
      (histopathological examination), enhanced lung edema (wet-to-dry weight ratio),
      and neutrophil infiltration (myeloperoxidase activity) at 6 h after LPS exposure.
      The analyses of bronchoalveolar lavage fluid showed the significant increases in
      pulmonary permeability (total cells and protein) and the levels of
      proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6). In contrast, these lung injury indexes were attenuated in
      rats that received a subcutaneous injection of GHRP-2 (100 microg/kg) 0.5 h prior
      to LPS administration. To further explore the potential anti-inflammatory
      mechanism of GHRP-2 in LPS-induced ALI, we assessed of nuclear factor-kappaB (NF
      kappaB) activity in lung tissues at 6 h after LPS challenge. We thus found that
      pretreatment with GHRP-2 markedly suppressed the activation of NF-kappaB in lung
      tissues. These results indicate that GHRP-2 attenuated LPS-induced ALI. Early
      protection appears to be mediated partly through the inhibition of NF-kappaB
      pathway activation. The present study indicates that GHRP-2 acts as a potential
      therapeutic reagent for treating ALI.

PMID- 20805680
TI  - Turkish female immigrants' intentions to participate in preconception carrier
      screening for hemoglobinopathies in the Netherlands: an empirical study.
AB  - BACKGROUND: Preconception carrier screening for hemoglobinopathies (HbPs) is
      debated in the Netherlands. OBJECTIVES: Intentions to participate in
      preconception carrier screening for HbPs as well as informed reproductive options
      were assessed in 109 Turkish female immigrants. METHOD: Participants completed a
      structured questionnaire. RESULTS: 83.5% of 109 Turkish female immigrants
      intended to participate in preconception carrier screening. Intention to
      participate was related to the desire to reduce uncertainty about having
      offspring affected by HbPs, but not with socio-demographic variables, risk
      estimation and worrying. If the tests concerning carrier status for HbPs were
      confirmative for both partners, 36.3% (n = 33) of the women with the intention of
      preconception carrier screening would refrain from getting children of their own,
      including 14.3% (n = 13) opting for adoption, 37.4% (n = 34) would decide to
      become pregnant and to opt for prenatal testing on HbPs. Finally, among 37.4% of
      the women opting for prenatal testing, 30.3% (n = 10) would terminate an affected
      pregnancy, 18.2% (n = 6) not and 51.5% (n = 17) could not decide (1 missing
      value). CONCLUSION: A large majority of Turkish female immigrants would
      participate in preconception carrier screening for HbPs.

PMID- 20805681
TI  - Quantitative mRNA analysis of serotonin 5-HT4 and adrenergic beta2 receptors in
      the mouse embryonic telencephalon.
AB  - The adrenergic beta2 receptor (beta2-AR) gene is embedded (nested) within the
      serotonin 5-HT4 receptor (5-HT4-R) gene and these two receptors can interact at
      the transcriptional and post-transcriptional levels. The mouse 5-HT4-R gene
      contains a number of exons and codes at least four mRNA splice variants (5
      HT(4(a))-R, 5-HT(4(b))-R, 5-HT(4(e))-R, 5-HT(4(f))-R), whereas the beta2-AR gene
      is intronless. Since 5-HT4-Rs and beta2-ARs can form homodimers and heterodimers
      and they increase intracellular cAMP levels, these receptors may be important for
      integrating serotonergic and noradrenergic signals at the single-neuron level.
      Both 5-HT4-R and beta2-AR have been implicated in autism spectrum disorders,
      depression, and Alzheimer's disease. In the fetal brain, these receptors may
      mediate the effects of stress on neurodevelopmental processes. We used
      quantitative reverse-transcription PCR (qRT-PCR) to investigate the developmental
      expression of 5-HT4-R and beta2-AR in the mouse telencephalon at embryonic days
      (E) 13-18. At E13-E14, the mRNA levels of all 5-HT4-R splice variants were very
      low, but by E17-E18 they increased 7-fold (5- HT(4(a))-R), 5-fold (5-HT(4(b))-R),
      9-fold (5-HT(4(e))-R), and 11-fold (5-HT(4(f))-R). The expression of 5-HT(4(a))-R
      and 5-HT(4(b))-R was rapidly upregulated between E14 and E15, at the time when
      the thalamocortical projections arrive in the telencephalon. This pattern was not
      observed in the expression of 5-HT(4(e))-R and 5-HT(4(f))-R, the mRNA levels of
      which showed a steady, gradual increase from E13 to E18. The beta2-AR mRNA levels
      were relatively high throughout the studied period of development and increased
      only by 70% from E13-E14 to E17-E18. These findings suggest that 5-HT4-R splice
      variants and beta2-ARs are differentially regulated in the embryonic
      telencephalon and that their relative amounts may carry developmentally important
      information.

PMID- 20805682
TI  - The neurodevelopment of empathy in humans.
AB  - Empathy, which implies a shared interpersonal experience, is implicated in many
      aspects of social cognition, notably prosocial behavior, morality and the
      regulation of aggression. The purpose of this paper is to critically examine the
      current knowledge in developmental and affective neuroscience with an emphasis on
      the perception of pain in others. It will be argued that human empathy involves
      several components: affective arousal, emotion understanding and emotion
      regulation, each with different developmental trajectories. These components are
      implemented by a complex network of distributed, often recursively connected,
      interacting neural regions including the superior temporal sulcus, insula, medial
      and orbitofrontal cortices, amygdala and anterior cingulate cortex, as well as
      autonomic and neuroendocrine processes implicated in social behaviors and
      emotional states. Decomposing the construct of empathy into subcomponents that
      operate in conjunction in the healthy brain and examining their developmental
      trajectory provides added value to our current approaches to understanding human
      development. It can also benefit our understanding of both typical and atypical
      development.

PMID- 20805683
TI  - Influenza in the elderly: a mini-review.
AB  - Influenza is an important cause of morbidity and mortality in the elderly
      population each year. The often subtle clinical manifestations in the frail
      geriatric patients may not be recognized initially, impeding timely
      administration of antiviral treatment. The effectiveness of current influenza
      vaccines in the elderly population is often diminished by immune senescence.
      Increasing immunization rates among health-care workers and elderly caregivers,
      and finding more effective vaccines for the elderly people are likely to
      significantly improve disease prevention in this population at risk.

PMID- 20805684
TI  - TLQP-21, a VGF-derived peptide, prevents ethanol-induced gastric lesions:
      insights into its mode of action.
AB  - BACKGROUND AND AIM: TLQP-21, a peptide derived from the vgf gene, has been
      reported to play a role in the regulation of rat gastric motility, but its
      influence on gastric mucosal integrity is unknown. EXPERIMENTAL APPROACH: We
      investigated the effects of central (0.8-8 nmol/rat) or peripheral (48-240
      nmol/kg) TLQP-21 administration on ethanol- (EtOH, 50%, 1 ml/rat) induced gastric
      lesions in the rat. The mechanisms involved in such activity were also examined.
      RESULTS: Central TLQP-21 injection dose-dependently reduced EtOH-induced gastric
      lesions (ED(50) = 3.16 nmol), while peripheral TLQP-21 administration had no
      effect. The TLQP-21 gastroprotective effect against EtOH injury was accompanied
      by a significant increase in gastric prostaglandin E(2) (PGE(2)) production
      linked to an increase in constitutive cyclooxygenase (COX) expression. The nitric
      oxide (NO) synthase inhibitor L-NAME (70 mg/kg, s.c.), the nonselective COX
      inhibitor indomethacin (10 mg/kg, orally) and capsaicin denervation removed TLQP
      21 gastroprotection. CONCLUSIONS: This study shows for the first time that
      central TLQP-21 exerts a protective action on the gastric mucosa exposed to the
      noxious agent EtOH. TLQP-21 gastroprotection is mediated by constitutive-derived
      NO and PGE(2), and requires the integrity of sensory nerve fibers.

PMID- 20805685
TI  - Significant associations between CCL5 gene polymorphisms and post
      transplantational diabetes mellitus in Korean renal allograft recipients.
AB  - BACKGROUND: Post-transplantational diabetes mellitus (PTDM) is a serious
      metabolic complication that may follow renal transplantation. The expression of
      chemokine (C-C motif) ligand 5 (CCL5) is inversely related to pancreatic beta
      cell function; thus, specific CCL5 gene polymorphisms are considered to be risk
      factors for diabetes. In this study, we investigated the association between CCL5
      gene polymorphisms and the occurrence of PTDM in Korean patients who had
      undergone renal transplants. METHODS: A total of 311 patients who had received
      kidney transplants without a prior history of diabetes were included. Three
      single nucleotide polymorphisms (SNPs) of the CCL5 gene were genotyped from
      genomic DNA with direct sequencing. RESULTS: PTDM developed in 56 patients
      (18.0%). The results showed that the allele frequencies of CCL5 gene
      polymorphisms, rs2107538*T, rs2280789*C and rs3817655*A were significantly higher
      in the patients with PTDM than in those without PTDM. In multiple logistic
      regression analysis, 3 SNPs (rs2107538, rs2280789 and rs3817655) of the CCL5 gene
      were significantly associated with the development of PTDM in the codominant 2
      and recessive models. Among haplotypes of the 3 polymorphisms, the frequency of
      the TCA haplotype was significantly higher in patients with PTDM than in those
      without PTDM. CONCLUSIONS: Our results indicated that genetic polymorphisms of
      the CCL5 gene were associated with PTDM, suggesting that the CCL5 gene might
      confer susceptibility to PTDM in patients who receive renal transplants.

PMID- 20805686
TI  - Casimir Funk: his discovery of the vitamins and their deficiency disorders.
AB  - The history of the discovery of vitamins is the history of their deficiency
      disorders. Their discoverer was Casimir Funk, who is considered the 'father of
      vitamin therapy'. In his experimental research, Funk studied the
      interrelationships in the human body of those elements that Eijkman had
      demonstrated in animals, particularly in birds. In his experimental research,
      Funk identified the dietetic factors whose lack caused the 'deficiency
      disorders', as he called human beri-beri, scurvy, rickets and pellagra. In 1911,
      he designated these factors 'vitamins' ('vita' = life, and 'amine' = a
      nitrogenous substance essential for life); this name was accepted by the
      scientific community in 1912.

PMID- 20805687
TI  - Cobb syndrome: case report and review of the literature.
AB  - Cobb syndrome is a rare non-inherited neurocutaneous disease, in which there are
      metameric cutaneous and spinal vascular malformations of the trunk. In cases of
      segmentally distributed multiple cutaneous vascular lesions, early diagnostic
      imaging of the spinal cord allows prompt intervention in order to reduce
      permanent neurological sequelae. We report case of Cobb syndrome in a 12-year-old
      boy and present a systematic review of the literature.

PMID- 20805688
TI  - Necrobiosis lipoidica therapy with biologicals: an ulcerated case responding to
      etanercept and a review of the literature.
AB  - Necrobiosis lipoidica (NL) is an idiopathic chronic granulomatous skin condition.
      There is currently no standardized effective treatment of NL. Ulceration occurs
      in up to 35% of cases. Treatment of ulcerative lesions is challenging and often
      unsuccessful. On the basis of the implication of the tumor necrosis factor alpha
      (TNF-alpha) on the formation of granulomas, since 2003 anti-TNF-alpha agents have
      been employed in cases of NL refractory to other therapeutic agents. We report a
      50-year-old white woman with treatment-resistant chronic ulcerative NL of both
      shins successfully treated with subcutaneous etanercept. A review of the
      published literature suggests that biological agents (etanercept and infliximab)
      should be considered as a therapeutic alternative mainly in ulcerative NL
      unresponsive to prior conventional regimens. The dose and duration of treatment
      with these agents is not defined, therefore it is required to report management
      of these patients in order to develop an optimal therapeutic strategy.

PMID- 20805689
TI  - Dermoscopy and in vivo reflectance confocal microscopy of a congenital nevus of
      the nipple.
AB  - We report a 26-year-old male with a 4 mm diameter, asymmetric, irregularly
      pigmented and bordered, brown maculopapular lesion on the right nipple present
      since childhood with enlargement of the lesion within the last 3 months.
      Dermoscopy revealed a global globular pattern with the presence of focally light
      brown globules and irregular black globules in its centre. In vivo reflectance
      confocal microscopy (RCM) revealed dense junctional and dermal melanocytic nests
      of different sizes and shapes that appeared as sharply demarcated round to oval
      reflective structures; cellular outlines of single melanocytes were not always
      detected. In the centre of the lesion within the upper dermis, irregularly
      shaped, homogeneously reflecting structures were observed. As a clear
      differentiation between clusters of melanophages and melanocytic nests could not
      be made with certainty, an excisional biopsy was performed to establish the
      diagnosis of compound nevus with features of congenital nevus. Therefore, to
      prove that dermoscopic globules correlated with melanophages, the correlation
      between dermoscopic RCM and histopathology was necessary.

PMID- 20805690
TI  - Do changes in relative blood volume monitoring correlate to hemodialysis
      associated hypotension?
AB  - INTRODUCTION: Intradialytic hypotension remains the most common complication for
      outpatient hemodialysis, and relative blood volume monitoring was designed to
      reduce hypotension. Reports of the usefulness of this technology, however, have
      been variable. METHODS: We audited the usefulness of relative blood volume
      monitoring recorded throughout the mid-week dialysis in 72 stable adult
      outpatients who had multifrequency bioimpedance measurements. RESULTS: The blood
      volume measurement (BVM) at the end of the session was 91.6 +/- 0.6% and was not
      different from the nadir BVM recorded (90.7 +/- 0.5). The BVM was strongly
      correlated with change in hematocrit (r = -0.56, p < 0.001) and albumin (r = 
      0.69, p < 0.001), but had no relationship with pre-, intra- or postdialysis blood
      pressure recordings. The BVM was not associated with ultrafiltration volume, but
      did correlate with a postdialysis change in extracellular fluid volume (r = 
      0.39, p = 0.006). CONCLUSION: In this audit, although the BVM at the end of the
      dialysis session was correlated with changes in hematocrit, serum albumin and
      extracellular fluid volume, the change in the relative BVM did not mirror changes
      in intradialytic blood pressure.

PMID- 20805691
TI  - When the earth trembles in the Americas: the experience of Haiti and Chile 2010.
AB  - The response of the nephrological community to the Haiti and Chile earthquakes
      which occurred in the first months of 2010 is described. In Haiti, renal support
      was organized by the Renal Disaster Relief Task Force (RDRTF) of the
      International Society of Nephrology (ISN) in close collaboration with Medecins
      Sans Frontieres (MSF), and covered both patients with acute kidney injury (AKI)
      and patients with chronic kidney disease (CKD). The majority of AKI patients
      (19/27) suffered from crush syndrome and recovered their kidney function. The
      remaining 8 patients with AKI showed acute-to-chronic renal failure with very low
      recovery rates. The intervention of the RDRTF-ISN involved 25 volunteers of 9
      nationalities, lasted exactly 2 months, and was characterized by major
      organizational difficulties and problems to create awareness among other rescue
      teams regarding the availability of dialysis possibilities. Part of the Haitian
      patients with AKI reached the Dominican Republic (DR) and received their therapy
      there. The nephrological community in the DR was able to cope with this extra
      patient load. In both Haiti and the DR, dialysis treatment was able to be
      prevented in at least 40 patients by screening and adequate fluid administration.
      Since laboratory facilities were destroyed in Port-au-Prince and were thus
      lacking during the first weeks of the intervention, the use from the very
      beginning on of a point-of-care device (i-STAT(r)) was very efficient for the
      detection of aberrant kidney function and electrolyte parameters. In Chile,
      nephrological problems were essentially related to difficulties delivering
      dialysis treatment to CKD patients, due to the damage to several units. This
      necessitated the reallocation of patients and the adaptation of their schedules.
      The problems could be handled by the local nephrologists. These observations
      illustrate that local and international preparedness might be life-saving if
      renal problems occur in earthquake circumstances.

PMID- 20805692
TI  - Elevated pro-brain natriuretic peptide, troponin T and malnutrition inflammatory
      score in chronic hemodialysis patients with overt cardiovascular disease.
AB  - BACKGROUND: We assessed the relationship between pro-brain natriuretic peptide
      (pro-BNP), troponin T (TropT) and nutritional status. METHODS: A total of 48
      chronic hemodialysis patients were grouped according to the presence [group A
      (GA); n = 24] or not [group B (GB)] of cardiovascular disease. RESULTS: Compared
      to GB subjects, GA subjects were older, had been on hemodialysis for a longer
      period and had higher prevalences of vascular grafts, hypertension and elevated C
      reactive protein (CRP) [GA vs. GB: 1.1 (range 0.1-32.9) vs. 0.4 (0-28.1) mg/dl; p
      = 0.028], malnutrition inflammatory score (MIS) (GA vs. GB: 7.50 vs. 4.00; p =
      0.001), pro-BNP [GA vs. GB: 6,760 (601-103,200) vs. 686 (75-83,700) pg/ml; p <
      0.001] and TropT [GA vs. GB: 0.3650 (0.011-0.199) vs. 0.010 (0.0-0.290) ng/ml; p
      = 0.002]. Pro-BNP correlated with TropT (rho 0.539; p < 0.001), MIS (rho 0.502; p
      < 0.0001), homocysteine (rho 0.321; p = 0.13) and CRP (rho 0.511; p < 0.0001).
      Pro-BNP levels were lower in GB patients as the body mass index increased; the
      opposite occurred in GA. CONCLUSIONS: Patients with cardiovascular disease had
      elevated pro-BNP and TropT levels. In patients without cardiovascular disease,
      malnutrition and inflammation were associated with vascular prostheses, while pro
      BNP was lower in obese patients.

PMID- 20805693
TI  - Founder mutations in the ATP6V1B1 gene explain most Cypriot cases of distal renal
      tubular acidosis: first prenatal diagnosis.
AB  - AIMS: To investigate clinically and genetically all the distal renal tubular
      acidosis (dRTA) cases in Cyprus, to study one more family from Greece and to
      perform the first dRTA prenatal diagnosis. We also tried to find any association
      with sensorineural hearing loss (SNHL) onset and particular mutations. METHODS:
      Nine dRTA families from Cyprus and one from Greece were analyzed for mutations in
      ATP6V1B1 gene by DNA resequencing and PCR-RFLPs. Clinical diagnosis was performed
      by standard criteria. Prenatal diagnosis was performed for one Cypriot family.
      RESULTS: Results show that 7/9 dRTA cases in Cyprus are caused by 229+1G>T and
      R157C founder mutations in ATP6V1B1 gene. 229+1G>T mutation was estimated to be
      older than 400 years. No genotype- phenotype correlation was found with SNHL. A
      known (L81P) and a novel mutation (912delT) were found in the Greek family.
      Prenatal diagnosis was performed for one Cypriot family, after parents' demand,
      showing that the embryo was a heterozygous carrier. CONCLUSION: Existence of only
      two ATP6V1B1 mutations in the Cypriot population is a diagnostic advantage. The
      age of onset of SNHL varies in our patients and probably is not related to
      ATP6V1B1 genotypes. Effective therapy for most of the syndrome symptoms is not
      satisfactory for some parents who choose prenatal diagnosis to ensure their
      child's health.

PMID- 20805694
TI  - Creatinine fluctuation has a greater effect than the formula to estimate
      glomerular filtration rate on the prevalence of chronic kidney disease.
AB  - BACKGROUND/AIMS: Cases of chronic kidney disease (CKD) are defined by the
      estimated glomerular filtration rate (eGFR), calculated using the Modified Diet
      in Renal Disease (MDRD) or, more recently, the CKD Epidemiology Collaboration
      (CKD-EPI) formula. This study set out to promote a systematic approach to
      reporting CKD prevalence. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: The
      study explores the impact of the way in which eGFR is calculated on the
      prevalence of CKD. We took into account whether including (1) ethnicity, (2)
      using a single eGFR, (3) using more than 1 eGFR value or (4) using the CKD-EPI
      formula affected the estimates of prevalence. SAMPLE: Of 930,997 registered
      patients, 36% (332,891) have their eGFR defined (63% of those aged 50-74 years,
      81% >75 years). RESULTS: The prevalence of stage 3-5 CKD is 5.41% (n = 50,331).
      (1) Not including ethnicity data the prevalence would be 5.49%, (2) just using
      the latest eGFR 6.4%, (3) excluding intermediary values 5.55% and (4) using the
      CKD-EPI equation 4.8%. All changes in eGFR (t test) and the proportion with CKD
      (chi(2) test) were significant (p < 0.001). Using serum-creatinine-calculated
      eGFR instead of laboratory data reduced the prevalence of stage 3-5 CKD by around
      0.01%. Sixty-six percent of people with stage 3-5 disease have cardiovascular
      disease and 4.0% significant proteinuria using the MDRD formula; the
      corresponding figures using CKD-EPI are 74 and 4.6%. CONCLUSIONS: A standardised
      approach to reporting case finding would allow a better comparison of prevalence
      estimates. Using a single eGFR tends to inflate the reported prevalence of CKD by
      ignoring creatinine fluctuation; this effect is greater than the difference
      between MDRD and CKD-EPI.

PMID- 20805695
TI  - Micro-sieving: isolation of whole glomeruli from a single renal needle biopsy
      sample.
AB  - Renal biopsy samples are important not only for the diagnosis of
      glomerulonephritis, but also for the investigation of its pathogenesis. However,
      it remains difficult to biochemically analyze proteins extracted solely from the
      glomeruli of needle biopsy samples, since the samples contain various components
      like renal tubules and connective tissue. Even a recent micro-dissection method,
      recovering the glomeruli in the sliced sections of the biopsy samples, has not
      fully solved the difficulty because the amount of obtainable proteins by this
      method is not usually enough for protein analysis. To overcome this problem, we
      established a simple but reliable method to isolate whole glomeruli from needle
      biopsy samples. By this method, termed 'micro-sieving', we were able to isolate
      on average more than 50 glomeruli from a single needle biopsy sample in an hour.
      The amount of the extracted glomerular proteins was on average 23 MUg per biopsy
      sample. As a representative use of this method, we were able to obtain a
      glomerular protein profile by fluorescent 2-dimensional electrophoresis for each
      of the tested patients with glomerulonephritis. 'Micro-sieving' can be used
      widely as a fundamental technique to analyze glomeruli in renal needle biopsy
      samples.

PMID- 20805696
TI  - Serum biological antioxidant potential predicts the prognosis of hemodialysis
      patients.
AB  - BACKGROUND: It is well known that oxidative stress is enhanced in patients with
      end-stage renal disease. However, little is known about the relationship between
      serum antioxidant capacity and clinical outcome in hemodialysis (HD) patients.
      METHODS: We examined the relationship between serum biomarkers of oxidative
      stress and clinical outcomes including all-cause mortality, hospitalization rate
      and incidence of cardiovascular events in HD patients. As biomarkers of oxidative
      stress, we measured serum levels of coenzyme Q10 (CoQ10) and biological
      antioxidant potential (BAP). RESULTS: 108 patients were observed for 30 months as
      the follow-up periods. The survival group (n = 83) showed significantly higher
      BAP values compared with those in death groups (n = 25; p < 0.05). When serum BAP
      levels were divided into two groups by their median value, the group with higher
      BAP values had a better survival rate than that with lower BAP values on the
      Kaplan-Meier survival analysis (p = 0.05). Although serum levels of CoQ10 did not
      show any association with clinical outcomes, lower BAP was selected as an
      independent risk factor for all-cause mortality as well as the absence of
      angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers therapy
      by age-adjusted Cox regression analysis. CONCLUSIONS: This study indicated that
      BAP could predict the prognosis of HD patients.

PMID- 20805697
TI  - beta2-Microglobulin, pulse pressure and metabolic alterations in hemodialysis
      patients.
AB  - BACKGROUND/AIM: Pulse pressure (PP) is a result of arterial stiffness seen in
      dialysis patients, but may be a consequence of fluid overload. We examined the
      role of beta(2)-microglobulin (beta(2)M) in PP in relation to metabolic
      alterations in patients on different hemodialysis (HD) modalities. METHODS: We
      studied 76 hemodialyzed patients on regular HD (n = 34), predilution bagged
      hemodiafiltration (n = 19) and online predilution hemodiafiltration (n = 23).
      beta(2)M levels were measured by radioimmunoassay, and the clearance of beta(2)M
      was assessed by Kt/V for beta(2)M. Arterial stiffness was measured as carotid
      femoral pulse wave velocity, and PP was derived. Insulin levels were measured
      using immunoradioassay, and insulin resistance was calculated using homeostasis
      model assessment insulin resistance (HOMA-IR). Serum bicarbonate levels were
      measured using a blood gas analyzer, and percent sodium removal was calculated.
      RESULTS: beta(2)M levels predict increased PP (p = 0.02) adjusting for age, HD
      modalities, HD duration, HOMA-IR and percent sodium removal. beta(2)M was
      positively associated with HOMA-IR (r = 0.306, p = 0.007). Serum bicarbonate
      levels and carotid-femoral pulse wave velocity were inversely associated (r = 
      0.719, p = 0.001). CONCLUSIONS: beta(2)M levels were positively associated with
      PP, which was influenced mainly by dialysis modality fluid and sodium balance and
      less by arterial stiffness. beta(2)M levels were positively associated with
      insulin resistance. Uremic acidosis may contribute to arterial stiffness.

PMID- 20805698
TI  - Association between albuminuria, glomerular filtration rate and mortality or
      recurrence in stroke patients.
AB  - BACKGROUND/AIMS: In an attempt to find new predictors of stroke prognosis, we
      evaluated the association of albuminuria (AUr) and the estimated glomerular
      filtration rate (eGFR) with the recurrence of stroke and mortality. METHODS: We
      evaluated and followed for at least 7 months patients with first-ever stroke or
      transient ischemic attack admitted to a prospective cohort from March 2005 to
      December 2007. We analyzed traditional CV risk factors, albumin-to-creatinine
      ratio and eGFR (ml/min/1.73 m(2)) as predictors of mortality or recurrence.
      RESULTS: From a total of 185 patients included [57% (104/185) men, 64 +/- 13
      years], 38 patients suffered from a recurrent stroke or died, with a mean follow
      up of 25.1 +/- 8.7 months. AUr (>=30 mg/g) was found in 50.2% (93/185), and 38.9%
      (72/185) presented an eGFR <60. In univariate analysis, age >65 years, eGFR <=50,
      atrial fibrillation (AF), no alcohol intake and AUr >17 mg/g were associated with
      the composite endpoint. In a multivariate analysis, AF and AUr >17 mg/g were
      independent predictors of the composite endpoints, but eGFR <=50 was not.
      CONCLUSION: The presence of AUr >17 mg/g is independently associated with death
      or recurrence after stroke. Further studies should consider the AUr as a
      predictor for a worse prognosis in these patients.

PMID- 20805701
TI  - Research ethics in the era of personalized medicine: updating science's contract
      with society.
AB  - With the completed sequence of the human genome has come the prospect of
      substantially improving the quality of life for millions through personalized
      medicine approaches. Still, any advances in this direction require research
      involving human subjects. For decades science and ethics have enjoyed an
      allegiance reflected in a common set of ethical principles and procedures guiding
      the conduct of research with human subjects. Some of these principles emphasize
      avoiding harm over maximizing benefit. In this paper we revisit the priority
      given to these ethical principles - particularly the principles that support a
      cautious approach to science - and propose a reframing of the 'social contract'
      between science and society that emphasizes reciprocity and meeting public needs.

PMID- 20805700
TI  - Public and biobank participant attitudes toward genetic research participation
      and data sharing.
AB  - Research assessing attitudes toward consent processes for high-throughput genomic
      wide technologies and widespread sharing of data is limited. In order to develop
      a better understanding of stakeholder views toward these issues, this cross
      sectional study assessed public and biorepository participant attitudes toward
      research participation and sharing of genetic research data. Forty-nine
      individuals participated in 6 focus groups; 28 in 3 public focus groups and 21 in
      3 NUgene biorepository participant focus groups. In the public focus groups, 75%
      of participants were women, 75% had some college education or more, 46% were
      African-American and 29% were Hispanic. In the NUgene focus groups, 67% of
      participants were women, 95% had some college education or more, and the majority
      (76%) of participants was Caucasian. Five major themes were identified in the
      focus group data: (a) a wide spectrum of understanding of genetic research; (b)
      pros and cons of participation in genetic research; (c) influence of credibility
      and trust of the research institution; (d) concerns about sharing genetic
      research data and need for transparency in the Policy for Sharing of Data in
      National Institutes of Health-Supported or Conducted Genome-Wide Association
      Studies; (e) a need for more information and education about genetic research. In
      order to increase public understanding and address potential concerns about
      genetic research, future efforts should be aimed at involving the public in
      genetic research policy development and in identifying or developing appropriate
      educational strategies to meet the public's needs.

PMID- 20805699
TI  - Single nucleotide polymorphisms in the phospholipase A2 receptor gene are
      associated with genetic susceptibility to idiopathic membranous nephropathy.
AB  - BACKGROUND: The phospholipase A(2) receptor (PLA2R) is a major antigen found in
      patients with idiopathic membranous nephropathy (MN). The relationship of genetic
      polymorphisms of PLA2R with the susceptibility and clinical outcomes of this
      disease is unknown. METHODS: We studied 199 patients with idiopathic MN followed
      up for 3.7 +/- 3.2 years. We enrolled 33 patients with secondary MN and 356
      subjects with normal blood pressure and no proteinuria. PLA2R single nucleotide
      polymorphisms (SNPs) were genotyped. RESULTS: The allele frequencies of C in
      rs35771982 and G in rs3828323 were 73.6 and 73.9%, respectively. Subjects with
      the CC genotype in rs35771982 had a higher susceptibility to idiopathic MN
      compared to subjects with other genotypes (odds ratio 2.6; 95% confidence
      interval 1.8-4.0). Patients with secondary MN were not different from controls
      with regard to PLA2R genotype. No impact of genetic polymorphisms on renal
      survival was detected. CONCLUSION: The findings of this study suggest that PLA2R
      SNPs might be associated with the risk of developing MN.

PMID- 20805702
TI  - [A case of del(16)(q22) in a patient with acute myeloid leukemia with complex
      karyotype].
AB  - Inversion of chromosome 16 [inv(16)(p13.1q22)] and t(16;16)(p13.1;q22) are
      associated with acute myelomonocytic leukemia (AMML) with eosinophilia and a
      favorable prognosis. On the other hand, patients with del(16)(q22) usually
      present with MDS or chronic myelomonocytic leukemia (CMML), which can evolve to
      AMML without eosinophilia, and this chromosomal aberration is associated with
      older age, a complex karyotype, and a poor prognosis. We report a case of AML
      with del(16)(q22) which showed a complex karyotype, absence of eosinophilia in
      bone marrow study and a poor response to chemotherapy.

PMID- 20805703
TI  - [A case of central nervous system myelomatosis with complex chromosome
      aberrations].
AB  - Involvement of the central nervous system is very uncommon in multiple myeloma,
      observed in approximately 1% of the multiple myeloma patients. We report a case
      of central nervous system myelomatosis with complex chromosome aberrations in a
      62-yr-old female patient, who had previously been diagnosed as multiple myeloma.
      Fluorescent in situ hybridization revealed 13q deletion, p53 gene deletion and
      IGH/FGFR3 rearrangement and chromosomal study showed complex chromosome
      aberrations. After four cycles of chemotherapy, the patient was admitted to the
      hematology department with severe headache. Plasma cells were found in the
      cerebrospinal fluid (CSF), and CSF immunoelectrophoresis revealed abnormal
      precipitin arcs against anti-IgG and anti-lambda antisera. She was given systemic
      chemotherapy and eight courses of intrathecal chemotherapy, which cleared plasma
      cells in the CSF. Two months later, she was given autologous stem cell
      transplantation. Three months after stem cell transplantation, central nervous
      system myelomatosis progressed to plasma cell leukemia and two months later, the
      patient expired.

PMID- 20805704
TI  - [Flow-assisted differential diagnosis of hemolytic anemia with spherocytosis: a
      case report].
AB  - In patients with hemolytic anemia associated with spherocytosis, differential
      diagnosis has to be made whether the hemolysis is immune-mediated or of non
      immune origin. We report a case of hereditary spherocytosis in a 12-yr-old male
      child, in whom flow-assisted diagnosis was made. In this case, diagnosis was not
      determined because routine laboratory workups for hereditary spherocytosis
      yielded discrepant RESULTS: positive osmotic fragility test, positive direct
      antiglobulin test, and normal result in the red cell membrane protein sodium
      dodecyl succinimide polyacrylamide gel electrophoresis. However, all flow
      cytometry-based tests, such as osmotic fragility, direct antiglobulin, and eosin
      5-maleimide binding test, yielded results compatible with hereditary
      spherocytosis. Additionally, in family study, the results of eosin 5-maleimide
      binding test suggested his disease being hereditary. In cases with diagnostic
      difficulties, flow cytometry may be used as an alternative tool, which can
      provide additional information in the differential diagnosis of hemolytic anemia
      with spherocytosis.

PMID- 20805705
TI  - [Comparison of HbA1c analyzers: D-10, Variant II Turbo, Cobas Integra 800, and
      Afinion AS100].
AB  - BACKGROUND: The purpose of this study was to evaluate the performance and
      agreement among HbA(1c) values measured using selected analyzers certified by the
      National Glycohemoglobin Standardization Program (NGSP) and standardized by the
      International Federation of Clinical Chemistry and Laboratory Medicine (IFCC).
      METHODS: HbA(1c) determined using D-10 (Bio-Rad, USA), Variant II Turbo (Turbo;
      Bio-Rad, USA), Cobas Integra 800 (Integra; Roche, Switzerland) and Afinion AS100
      (Afinion; Axis-Shield, Norway) were compared with each other. Precision and
      method comparisons with Deming regression were evaluated according to CLSI
      recommendations. We also compared the HbA(1c) values obtained with each analyzer
      using either IFCC or NGSP methods by correlation analysis and kappa statistics.
      RESULTS: The repeatability and method/device precisions of D-10 and Afinion were
      acceptable. The correlation coefficients of HbA(1c) were 0.986 for D-10 vs.
      Afinion, 0.997 for D-10 vs. Turbo, 0.988 for D-10 vs. Integra, and 0.991 for
      Integra vs. Afinion. The average biases of HbA(1c) Afinion (IFCC) and HbA(1c)
      Integra (IFCC) against HbA(1c) D-10 (NGSP) were -1.90% and -1.79%, respectively.
      Kappa agreement statistics for the three diabetic control group HbA(1c) values of
      "less than 6.5%," "6.5%-7.5%," and "greater than 7.5%" for D-10 vs. Turbo, D-10
      vs. Integra, and D-10 vs. Afinion were 0.872, 0.836, and 0.833, respectively.
      CONCLUSIONS: The strong correlations and good clinical agreements of HbA(1c)
      between each analyzer expressed in terms of either NGSP or IFCC-derived NGSP
      indicate that these analyzers can be used interchangeably.

PMID- 20805706
TI  - [Determination of urinary iodine concentration by inductively coupled plasma-mass
      spectrometry in thyroid cancer patients on low-iodine diet].
AB  - BACKGROUND: Thyroid cancer patients should be on low-iodine diet (LID) before
      radioactive iodine therapy (RAIT) to maximize the effect of RAIT. Urinary iodine
      excretion is the most accurate marker of very recent dietary iodine intake. We
      developed and evaluated the analytical performance of inductively coupled plasma
      mass spectrometry (ICP-MS) to determine urinary iodine concentration. METHODS: We
      evaluated the linearity, precision, accuracy, and lower limit of quantification
      (LLOQ) of an ICP-MS method (Agilent 7500ce) to determine urinary iodine
      concentration in accordance with the Food and Drug Administration (FDA)
      guidelines for bioanalytical method validation. This method was used to determine
      and compare the iodine concentration in random urine samples of 120 thyroid
      cancer patients on LID for 1 week and 80 healthy adults on normal diet. RESULTS:
      Our ICP-MS method showed good linearity (1.0-1,913 microg/L; R(2)>0.999). Both
      intra-day and inter-day precision CV were within 20% for the LLOQ (1 microg/L)
      and within 15% for the other concentrations. Accuracy was 110-120% for the LLOQ
      and 95-115% for the other concentrations. The median concentration of iodine in
      random urine samples from thyroid cancer patients on LID (38.7 microg/L) was
      significantly lower than that of healthy subjects (238.8 microg/L) (P<0.0001).
      CONCLUSIONS: Urinary iodine analysis by ICP-MS showed good linearity, precision,
      accuracy, wide measuring range of detection, and lower LLOQ. This method will be
      very useful to evaluate the status of dietary iodine intake and the
      appropriateness of LID in thyroid cancer patients, thereby maximizing the effect
      of RAIT.

PMID- 20805707
TI  - [Study on interpretation of quantitative results of prostate-specific antigen
      using information theory].
AB  - BACKGROUND: The prostate-specific antigen (PSA) is considered the most useful
      among tumor markers currently used. However, its quantitative results are
      interpreted only qualitatively for the diagnosis of prostate cancer. The recently
      introduced information theory enables the information of the quantitative results
      transformed into Shannon's entropy (S) that represents uncertainties and then "1
      S" representing diagnostic certainty. METHODS: The 882 urological patients
      enrolled were categorized into 2 groups: a patient group comprising 233 patients
      with prostate cancer and a disease control group comprising 649 patients with
      benign prostate disease. The level of PSA in all the patients was tested and was
      found to be >or=2 ng/mL. The variables like PSA level and age were modeled on
      logistic regression analysis to predict the probability of prostate cancer and
      the diagnostic certainty. RESULTS: The mean (SD) of PSA levels in the patient
      group and the disease control group were 44.5 ng/mL (37.62 ng/mL) and 5.7 ng/mL
      (3.70 ng/mL), respectively. The logistic regression model fitted well when the
      age variable was dichotomized at the age of 55 yr. The diagnostic certainty was
      lowest at a PSA level of 18.90 ng/mL in the <55-yr age group, and 15.45 ng/mL in
      the >55-yr age group. CONCLUSIONS: The diagnostic certainty (1-S) of whether to
      diagnose prostate cancer or not at a certain PSA level could be obtained using
      the information theory. The methodology used in this study may help interpret the
      results of other quantitative tests.

PMID- 20805708
TI  - [Species distribution and antifungal susceptibilities of yeast clinical isolates
      from three hospitals in Korea, 2001 to 2007].
AB  - BACKGROUND: We utilized results from the ARTEMIS DISK Global Antifungal
      Surveillance Program to evaluate the species distribution and fluconazole and
      voriconazole susceptibilities of yeast isolates from clinical specimens in South
      Korea from 2001 to 2007. METHODS: Data were collected on 5,665 yeast isolates
      from all body sites at three locations. All investigators tested clinical yeast
      isolates using the CLSI M44-A disk diffusion method. Test plates were
      automatically read and results were recorded using the BIOMIC image analysis
      plate reader system (Giles Scientific, USA). Species, drug, zone diameter,
      susceptibility category, and quality control results were collected quarterly via
      e-mail for analysis. RESULTS: Candida albicans was the most common isolate, but a
      progressive increase in non-C. albicans Candida and noncandidal yeast species has
      been observed in recent years. The overall percentages of isolates in each
      category (susceptible, susceptible dose dependent, and resistant) were 98.8%,
      0.5%, and 0.7% and 99.2%, 0.2%, and 0.6% for fluconazole and voriconazole,
      respectively. Candida of 3 species exhibited decreased susceptibility to
      fluconazole (<90% S) in the order of that seen with the resistant (R) species: C.
      krusei, C. guilliermondii, and C. glabrata. Emerging resistance to fluconazole or
      voriconazole was documented among isolates of Cryptococcus neoformans,
      Trichosporon spp., and Rhodotorula spp. CONCLUSIONS: The species distribution and
      antifungal susceptibilities of yeasts may differ according to specimen type,
      testing method, hospital, and geographic region. Therefore, further large-scaled,
      long-term surveillance studies are needed to isolate yeasts and to confirm the
      species distribution and antifungal susceptibilities of yeast isolates from
      clinical specimens in Korea.

PMID- 20805709
TI  - [Evaluation of MicroScan Synergies plus Positive Combo 3 Panels for
      identification and antimicrobial susceptibility testing of Staphylococcus aureus
      and Enterococcus species].
AB  - BACKGROUND: Few studies have evaluated the performance of the recently introduced
      MicroScan Synergies plus Positive Combo 3 Panels (SIPC3) (Dade Behring Inc.,
      USA). We evaluated the clinical efficacy of the panels in identification (ID) and
      antimicrobial susceptibility testing (AST) of Staphylococcus aureus and
      enterococci. METHODS: To evaluate the panels' accuracy of identification, the
      results obtained using the test panels were compared with those obtained by using
      conventional biochemical tests in conjunction with VITEK 2 system (bio-Merieux,
      USA). In addition, the AST results obtained using the panels were compared with
      those obtained by performing CLSI broth microdilution. RESULTS: The overall
      agreement between the approaches for the ID of S. aureus and enterococci was 100%
      and 96%, respectively. The categorical and essential agreements (CA and EA) for
      S. aureus were 98%, each. Very major errors (VME), major errors (ME), and minor
      error (mE) for S. aureus were 0.45%, 0.3%, and 4.2%, respectively. The majority
      of VMEs were for oxacillin (8.6%), penicillin (2.0%), erythromycin (7.9%),
      clindamycin (3.8%), and tetracycline (4.1%). For enterococci, the CA, EA, VME,
      ME, and mE were 88.8%, 93.7%, 4.4%, 0%, and 2.8%, respectively. The 80.5% (29/36)
      of Enterococcus faecium had concordant ID with the reference. Most of the
      categorical errors (3 VMEs and 14 mEs) were observed for
      quinupristin/dalfopristin (Synercid; Catalytica Pharmaceuticals Inc., USA).
      CONCLUSIONS: The panels compared favorably with conventional methods for the ID
      and AST of S. aureus. However, we expected a better performance for ID of E.
      faecium and AST using Synercid.

PMID- 20805710
TI  - [A comparison analysis on the diagnosis of Helicobacter pylori infection and the
      detection of clarithromycin resistance according to biopsy sites].
AB  - BACKGROUND: This study was performed to determine the biopsy sites that are
      suitable for the diagnosis of Helicobacter pylori infection and to assess the
      sensitivity of culture, histology, and dual-priming oligonucleotide (DPO)-based
      multiplex PCR. Moreover, we evaluated the usefulness of PCR for the detection of
      23S rRNA mutations, which are responsible for the clarithromycin resistance of H.
      pylori. METHODS: From 90 patients, we obtained biopsy specimens for culture,
      histology, and Seeplex ClaR-H. pylori PCR (Seegene Inc., Korea). Phenotypic
      susceptibility to clarithromycin was evaluated using the E-test (AB Biodisk,
      Sweden). RESULTS: H. pylori was detected in 48 of 90 patients. The positive rates
      of infection in the antrum and body were higher than those in the biopsies
      obtained from the duodenal bulb. The positive rates in histology, PCR, and
      culture were 46.7%, 42.2%, and 34.4%, respectively. Using histology or PCR, we
      identified H. pylori in 46 of the 48 patients. 23S rRNA mutations were detected
      in 8 patients. The clarithromycin E-test showed that all the 10 wild-type
      patients were susceptible. However, the results of the PCR and E-test of 3 of the
      8 mutation-positive patients were discrepant. CONCLUSIONS: We observed that a
      combination of histology and PCR affords a high detection rate of H.pylori
      infection and that DPO-based PCR can be practically used for the diagnosis of H.
      pylori infection and the determination of clarithromycin resistance. These
      techniques were useful for biopsy sampling simultaneously from the antrum and
      body for the detection of clarithromycin resistance of multiple strain infection
      or heteroresistance.

PMID- 20805711
TI  - [Novel influenza A (H1N1) infection in immunocompromised patients].
AB  - BACKGROUND: Since April 2009, novel influenza A (H1N1) infection is spreading
      throughout the world. This infection might be fatal for immunocompromised
      patients who are at a potentially high risk of developing infectious
      complications. We investigated the detection rate and features of H1N1 infection
      in immunocompromised patients. METHODS: Between August 2009 and February 2010, we
      examined 8,112 subjects, including 390 immunocompromised patients, for H1N1. Swab
      samples were taken from the nose and throat of the participants. Real-time PCR
      was performed to identify H1N1 viral genes. RESULTS: Positive results were
      obtained in 2,953/8,112 (36.4%) subjects and 46/390 (11.8%) immunocompromised
      patients. H1N1 was identified in 8.7% patients with solid cancer, 12.9% patients
      with hematologic malignancy, 16.7% patients with chronic renal disease, and 14.5%
      patients with kidney transplantation. The mean cycle threshold (Ct) value of PCR
      was significantly lower (P<0.05) in patients with hematologic malignancy as
      compared to that in patients with chronic renal disease and control subjects.
      Four patients died due to respiratory complications. CONCLUSIONS: The detection
      rate of H1N1 was significantly lower in immunocompromised patients than in other
      patients. The Ct value of patients with hematologic malignancy was significantly
      lower than that of other immunocompromised patients and control subjects.

PMID- 20805712
TI  - [Usefulness of a chromogenic selective agar for the identification of Bacillus
      cereus isolated from blood cultures].
AB  - BACKGROUND: The incidence of Bacillus cereus bacteremia is increasing, but the
      identification of Bacillus species remains difficult. Brilliance Bacillus cereus
      agar (BBC agar; Oxoid, UK) is a new CHROMagar medium that allows selective
      isolation and identification of B. cereus; however, its clinical usefulness is
      seldom studied. We evaluated the usefulness of BBC agar to identify B. cereus
      isolates recovered from blood cultures. METHODS: We analyzed a total of 53 blood
      isolates that showed a Bacillus-like morphology on Gram staining. All isolates
      were identified by using both the API Coryne (bioMerieux, France) and API 50CH/B
      (bioMerieux) systems. They were subsequently subcultured on BBC agar, incubated
      for 24 hr, and then examined for characteristic blue-green colonies. The clinical
      characteristics of patients whose isolates were identified as B. cereus were
      assessed. RESULTS: Of the 53 isolates, 18 were identified as B. cereus by API
      50CH/B. With the API 50CH/B system used as gold standard, the sensitivity and
      specificity for the identification of B. cereus were 100% (18/18) and 100%
      (35/35), respectively, using BBC agar, and 67% (12/18) and 100% (35/35),
      respectively, using the API Coryne system. Of the 18 patients with B. cereus
      bacteremia, 15 showed infectious signs, and 3 had more than 2 blood cultures
      positive for B. cereus on separate days. CONCLUSIONS: Our study shows, for the
      first time, that BBC agar, with its good agreement and ease of use, is a valuable
      alternative to the API 50CH/B system for the presumptive identification of B.
      cereus isolates from blood cultures.

PMID- 20805713
TI  - [A case of disseminated Penicillium marneffei infection in a liver transplant
      recipient].
AB  - Penicillium marneffei is the only dimorphic fungus among Penicillium spp. that
      can cause a fatal infection in immunocompromised patients. P. marneffei is
      endemic in Southeast Asia and eastern China. P. marneffei infection is an AIDS
      defining illness and the third most common opportunistic infection in the endemic
      regions. Here, the authors report a case of disseminated P. marneffei infection
      in a patient who underwent liver transplantation in China. During the hospital
      stay, the mold form of the fungus that produced a red wine-colored pigment on the
      agar plate was isolated from the patient's urine, transtracheal aspirate, and
      blood. The fungus was identified as P. marneffei by direct sequencing of the D1
      D2 and ITS regions. Thermal dimorphism was also confirmed by subculturing the
      colony at 37 degrees C. To the best of our knowledge, this is the first Korean
      case of disseminated P. marneffei infection in a liver transplant recipient.

PMID- 20805714
TI  - Clinical significance of serum procalcitonin in patients with community-acquired
      lobar pneumonia.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is a common respiratory disorder
      in children, which necessitates hospitalization. Bacterial pneumonia, especially
      lobar pneumonia and parapneumonic effusions, is associated with considerably
      severe clinical course and extensive alveolar infiltrates. Serum procalcitonin
      (PCT) level has been used to distinguish bacterial from viral infections, but its
      usefulness is disputed. The diagnostic accuracy and usefulness of PCT, C-reactive
      protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell (WBC)
      count were determined by comparing their values in the patients with CAP with
      those in healthy controls. METHODS: The serum PCT levels, as well as CRP level,
      ESR, and WBC counts, were measured in 76 hospitalized patients with CAP (lobar
      pneumonia, 16; bronchopneumonia, 60) and 18 healthy controls. Serum PCT level was
      measured using VIDAS BRAHMS PCT (Biomerieux, France), and ROC curve analysis was
      performed to evaluate its diagnostic accuracy. RESULTS: Serum PCT levels were
      higher in the patients with CAP than in healthy controls, especially in the
      patients with lobar pneumonia than in those with bronchopneumonia. Serum CRP
      level was also significantly elevated in the patients with CAP, especially in
      those with lobar pneumonia. The diagnostic accuracy of serum PCT level for the
      diagnosis of lobar pneumonia was better than those of serum CRP level and ESR.
      The serum PCT level was significantly correlated with the CRP level, ESR, and WBC
      count. CONCLUSIONS: Serum PCT level was a better marker than CRP level or ESR for
      the diagnosis of lobar pneumonia in children with CAP.

PMID- 20805715
TI  - [Analysis of patients with positive acid-fast bacilli culture and negative T
      SPOT.TB results].
AB  - BACKGROUND: T-SPOT.TB is a sensitive test that detects interferon-gamma producing
      T-cells in tuberculosis patients following stimulation with tuberculosis-specific
      antigens. Our study was aimed to investigate the possible causes of false
      negative results of the test by analyzing the patients with positive acid-fast
      bacilli (AFB) culture and negative T-SPOT.TB results. METHODS: We investigated
      138 patients with positive AFB culture results reported between January 2009 and
      April 2010. Medical records of these patients were reviewed for the results of T
      SPOT.TB test, AFB culture, PCR for Mycobacterium tuberculosis (TB-PCR), chest X
      ray, drug treatment, etc. Diagnosis of tuberculosis was confirmed by positive TB
      PCR or identification of Mycobacterium tuberculosis (MTB). Sensitivity of T
      SPOT.TB test was calculated and the possible causes of AFB culture positive and T
      SPOT.TB negative results were analyzed. RESULTS: T-SPOT.TB test was performed in
      63 of the 138 patients with AFB culture positive results. Fifty-six (88.9%) were
      positive and 7 patients (11.1%) were negative on T-SPOT.TB test. Of these 7
      negative cases, 4 were confirmed as nontuberculous mycobacteria (NTM), 2 were
      suspected as NTM and diagnosis could not be confirmed in 1. Six of these 7
      patients were over 70 yr old and 6 patients had lymphocytopenia. T-SPOT.TB
      negative results were not observed in any of the 44 patients confirmed to have
      active tuberculosis (sensitivity 100%). CONCLUSIONS: Our results suggest that T
      SPOT.TB test is very sensitive for diagnosing active tuberculosis. NTM may be the
      main cause of AFB culture positive and T-SPOT.TB negative results, but MTB
      infection in immunocompromised patients also has to be considered.

PMID- 20805716
TI  - [Detection of allergen specific IgE by AdvanSure Allergy Screen test].
AB  - BACKGROUND: In vitro serum allergen-specific IgE tests have been routinely used
      in the clinical diagnosis of allergic diseases. We evaluated the clinical
      usefulness of a newly introduced multiple antigen screen test, Advansure Allergy
      Screen (LG Life Science, Korea) (LG-Screen) for the detection of allergen
      specific IgE. METHODS: A total of 180 sera (80 for inhalant and 100 for food
      panels) were tested by LG-Screen and RIDA Allergy Screen (R-biopharm, Germany)
      (RIDA-Screen) assays. According to the 58-60 specific allergens or allergen
      groups, the positive rates and agreement rates were analyzed using the cut off
      levels of class 2. For the quantitation of total IgE and specific IgE,
      nephelometry and ImmunoCAP test were performed in the sera showing discrepant
      results between the two allergy screen assays. RESULTS: The agreement rate and
      kappa value (k) of total IgE between the two allergy screen assays was 73.9% and
      0.333. LG-Screen showed higher agreement rate with nephelometry than RIDA-Screen.
      The positive rates to common outdoor inhalant and food allergens were
      significantly higher in RIDA-Screen. Overall agreement rate of specific IgE
      between the two allergy screen assays for 58 allergens was 86.7% (6,086/7,020)
      (k, 0.293). In samples showing discrepant results between the two allergy screen
      assays, concordance rate of allergy screen assay with ImmunoCAP assay was 70.9%
      (449/633) for LG-Screen (k, 0.585) and 29.1% (184/633) for RIDA-Screen (k, 
      0.303). CONCLUSIONS: LG-Screen showed a favorable agreement with RIDA-Screen and
      ImmunoCAP assays, and it could be used for the detection of allergen specific IgE
      in the clinical laboratory.

PMID- 20805717
TI  - [Evaluation of a multiplex PCR kit used for detecting Y chromosome
      microdeletions].
AB  - BACKGROUND: In addition to Klinefelter's syndrome, microdeletion of Yq is the
      most common genetic cause of male infertility; 15% of azoospermic or 5-10% of
      oligozoospermic males have Yq deletions. We evaluated a Yq microdeletion kit (LG
      Life Sciences, Korea) for identifying microdeletions in the azoospermic factor
      (AZF) regions of the Yq. METHODS: The kit was designed to amplify 3 regions of
      the AZF gene (AZFa, AZFb, and AZFc) using 15 sequence-tagged sites. We evaluated
      the preclinical performance of the kit. For clinical validation, 58 patients
      including 25 idiopathic azoospermic or oligozoospermic patients were examined.
      RESULTS: We observed clear bands on electrophoresis of DNA, up to a DNA
      concentration of 3.12 ng/microL; the known microdeletion regions of all 6
      reference cell-lines (Coriell, USA) were accurately detected and no false
      positive/negative results showed with normal female (n=11) and fertile male
      (n=15) specimens. This kit could identify the same microdeletions in the common
      regions, similar to another commercial kit. Among the 58 male infertile patients,
      7 (12.1%) had microdeletions of the Yq. Among the idiopathic azoospermic (n=22)
      and oligozoospermic (n=3) patients, 3 (12.0%) had microdeletions. Further, 2 of
      21 varicocele patients (9.5%), 1 of 4 patients with testicular failure, and 1
      patient with a 45,X/46,XY mosaic had microdeletions. CONCLUSIONS: The kit was
      effective for detecting microdeletions of the Yq. We identified microdeletions in
      12% of the infertile patients. This Y chromosome microdeletion detection kit is
      useful for screening Yq microdeletions in infertile patients.

PMID- 20805718
TI  - [A case of pseudoisodicentric chromosome 18q detected at prenatal diagnosis].
AB  - Although trisomy 18 (Edwards' syndrome) or the terminal deletion syndromes of 18p
      and 18q have been occasionally detected, pseudoisodicentric chromosome 18 is a
      very rare constitutional chromosomal abnormality. We describe a case of
      pseudoisodicentric chromosome 18q without mosaicism, which was confirmed from
      fetal cells in the amniotic fluid used for prenatal diagnosis of multiple
      congenital anomalies. A 23-yr-old pregnant woman was suspected of having a fetal
      anomaly at 18(+3) weeks gestation. In sonography, the fetus showed multiple
      anomalies: bilateral overt ventriculomegaly in the brain, ventricular septal
      defect and valve anomaly in the heart, bilateral club foot, polydactyly,
      meningocele, and a single umbilical artery. The pregnancy was terminated and a
      conventional G-banded chromosome study was performed using amniotic fluid. Twenty
      metaphase cells among the cultured amniocytes showed a 46,XX,psu idic(18)(q22).
      Consequently, the fetus had partial trisomy (18pter-->q22) and partial monosomy
      (18q22-->qter). Both parents were confirmed to have a normal karyotype.

PMID- 20805719
TI  - [Proposal of laboratory test panel based on patients' chief complaints in
      emergency department].
AB  - BACKGROUND: A test panel is a group of tests that are simultaneously performed
      for diagnosis and follow-up of patients. Organ-specific or disease-specific test
      panels are currently available. Since the patient's chief complaint plays a key
      role in obtaining the personal and medical history and performing physical
      examinations, we proposed a test panel based on the chief complaints of the
      patients. METHODS: We collected data from 3,127 adults with apparent symptoms who
      visited the emergency department from April 2009 to May 2009. Subsequently, we
      classified the patients' chief complaints, ordered the laboratory tests on the
      basis of these complaints, considered the patients' disease entities, and
      reviewed the relevant literature. RESULTS: The patients were categorized into 14
      groups on the basis of the most common chief complaints presented in the
      emergency department. We first selected the basic test panels and then organized
      the test panel for each chief complaint to enable differential diagnosis.
      CONCLUSIONS: We proposed test panels based on the chief complaints of the
      patients; these test panels could allow rapid diagnosis and be more useful than
      the organ-specific or disease-specific tests in critical pathway development. The
      next step will be evaluating the efficiency and cost effectiveness of the test
      panel that we suggested.

PMID- 20805720
TI  - European Journal of Emergency Medicine: state of the union.

PMID- 20805721
TI  - Pulmonary nocardiosis masquerading as severe community-acquired pneumonia.

PMID- 20805722
TI  - Respiratory distress in children: another cause to be considered.

PMID- 20805723
TI  - Reply to Dr Lockey et al.'s remarks on prehospital thoracostomy.

PMID- 20805724
TI  - ECT in the 21st century: optimizing treatment: state of the art in the 21st
      century.

PMID- 20805725
TI  - A novel positioning technique for the agitated patient after electroconvulsive
      therapy: gravitational restraint.
AB  - We present a novel positioning technique to assist in the gentle and safe
      management of the postictal agitated patient.

PMID- 20805727
TI  - A review of continuation electroconvulsive therapy: application, safety, and
      efficacy.
AB  - Electroconvulsive therapy (ECT) is a neurostimulation therapeutic intervention
      that is highly effective and frequently used to treat certain psychiatric
      conditions, particularly major depressive disorder. Despite its high efficacy, a
      major limitation of ECT is the significant rate at which patients relapse after
      treatment. Providing additional ECT treatments after completion of a short-term
      course of ECT, referred to as continuation ECT (C-ECT), is a strategy used to
      reduce the risk of relapse. Specifically, C-ECT involves the administration of
      additional ECT treatments during the 6-month period after remission. This article
      summarizes the available literature regarding C-ECT including indication for use,
      patient selection, treatment guidelines/parameters, and safety. The efficacy of C
      ECT is also discussed, with a focus on major depressive disorder and
      schizophrenia. On the basis of the current literature, indications for use and
      patient selection for C-ECT are predominately similar to those for a short-term
      ECT course. The treatment guidelines/parameters for C-ECT are recommended to be
      consistent with the parameters used to achieve remission, with the exception of
      greater intertreatment intervals during C-ECT. Although adverse cognitive effects
      can occur during C-ECT, the risk and severity of cognitive impairment are
      generally low, possibly because of the greater intertreatment intervals. Most
      research supports the use of C-ECT to prolong remission; however, methodologic
      limitations mitigate firm conclusions and generalizability of these findings.
      Nonetheless, the available evidence supports the use of C-ECT as a safe and
      effective method in relapse prevention.

PMID- 20805729
TI  - Making optimal use of available molybdenum-99.

PMID- 20805726
TI  - Electroconvulsive therapy stimulus parameters: rethinking dosage.
AB  - In this article, we review the parameters that define the electroconvulsive
      therapy (ECT) electrical stimulus and discuss their biophysical roles. We also
      present the summary metrics of charge and energy that are conventionally used to
      describe the dose of ECT and the rules commonly deployed to individualize the
      dose for each patient. We then highlight the limitations of these summary metrics
      and dosing rules in that they do not adequately capture the roles of the distinct
      stimulus parameters. Specifically, there is strong theoretical and empirical
      evidence that stimulus parameters (pulse amplitude, shape, and width, and train
      frequency, directionality, polarity, and duration) exert unique neurobiological
      effects that are important for understanding ECT outcomes. Consideration of the
      distinct stimulus parameters, in conjunction with electrode placement, is central
      to further optimization of ECT dosing paradigms to improve the risk-benefit
      ratio. Indeed, manipulation of specific parameters, such as reduction of pulse
      width and increase in number of pulses, has already resulted in dramatic
      reduction of adverse effects, while maintaining efficacy. Furthermore, the
      manipulation of other parameters, such as current amplitude, which are commonly
      held at fixed, high values, might be productively examined as additional means of
      targeting and individualizing the stimulus, potentially reducing adverse effects.
      We recommend that ECT dose be defined using all stimulus parameters rather than a
      summary metric. All stimulus parameters should be noted in treatment records and
      published reports. To enable research on optimization of dosing paradigms, we
      suggest that ECT devices provide capabilities to adjust and display all stimulus
      parameters.

PMID- 20805728
TI  - Adjunctive psychotropic medications during electroconvulsive therapy in the
      treatment of depression, mania, and schizophrenia.
AB  - Current guidelines regarding concomitant antidepressants during electroconvulsive
      therapy (ECT) are inconsistent. Although the American Psychiatric Association
      Task Force on ECT discouraged combination antidepressant treatment, owing to the
      minimal evidence for enhanced efficacy and concern about increased adverse
      effects, combination treatment is recommended and considered routine for many
      practitioners in the United States and other parts of the world. Considering the
      increasing levels of treatment resistance among patients referred for ECT and the
      high relapse rate after acute ECT, the role of concomitant antidepressant
      pharmacotherapy during ECT should be reevaluated. More research, however, is
      needed to explore the impact of administering specific antidepressants during
      acute and maintenance ECT (M-ECT), on antidepressant efficacy and cognitive
      adverse effects. This will require appropriately controlled studies of ECT
      medication combinations that include attention to a range of cognitive function
      measures and clinical response. In addition, the role of combination ECT and
      psychotropic medication in the treatment of mania and schizophrenia continues to
      receive attention, particularly in those patients who have shown inadequate
      responses to psychotropic medication alone. Although there is insufficient
      evidence to support the routine addition of antipsychotic medications to ECT
      during the treatment of acute mania, the literature suggests that it is
      unnecessary to discontinue antipsychotic medication when ECT is added to the
      treatment of a manic patient that has been unresponsive to pharmacological
      treatment. Despite the lack of well-controlled studies, the existing literature
      suggests that combination ECT and antipsychotic treatment is a useful option for
      patients with schizophrenia who are unresponsive to pharmacological interventions
      alone, and its adverse effect profile does not seem different from that seen with
      ECT alone.

PMID- 20805731
TI  - Current techniques for MR imaging of atherosclerosis.
AB  - Vessel wall imaging of large vessels has the potential to identify culprit
      atherosclerotic plaques that lead to cardiovascular events. Comprehensive
      assessment of atherosclerotic plaque size, composition, and biological activity
      is possible with magnetic resonance imaging (MRI). Magnetic resonance imaging of
      the atherosclerotic plaque has demonstrated high accuracy and measurement
      reproducibility for plaque size. The accuracy of in vivo multicontrast MRI for
      identification of plaque composition has been validated against histological
      findings. Magnetic resonance imaging markers of plaque biological activity such
      as neovasculature and inflammation have been demonstrated. In contrast to other
      plaque imaging modalities, MRI can be used to study multiple vascular beds
      noninvasively over time. In this review, we compare the status of in vivo plaque
      imaging by MRI to competing imaging modalities. Recent MR technological
      improvements allow fast, accurate, and reproducible plaque imaging. An overview
      of current MRI techniques required for carotid plaque imaging including hardware,
      specialized pulse sequences, and processing algorithms are presented. In
      addition, the application of these techniques to coronary, aortic, and peripheral
      vascular beds is reviewed.

PMID- 20805733
TI  - Progression in atherosclerosis: histological features and pathophysiology of
      atherosclerotic lesions.
AB  - In this article, we present an illustrated and brief review of the literature
      concerning the histological and pathophysiological features of human
      atherosclerosis. Although the basic descriptive terms remain unchanged, the
      classification systems have evolved, and a uniform terminology is essential in
      clinical and laboratory researches. We discuss the major difficulties in
      classifying atherosclerotic lesions and give an overview of the most important
      histological classification systems as provided by the American Heart Association
      and Virmani et al (Arterioscler Thromb Vasc Biol. 2000;20:1262). Furthermore, we
      present the most recent literature concerning plaque progression, including
      enlargement of the lipid core and neovascularization.

PMID- 20805732
TI  - Advanced techniques for MRI of atherosclerotic plaque.
AB  - This review examines the state of the art in vessel wall imaging by magnetic
      resonance imaging (MRI) with an emphasis on the biomechanical assessment of
      atherosclerotic plaque. Three areas of advanced techniques are discussed. First,
      alternative contrast mechanisms, including susceptibility, magnetization
      transfer, diffusion, and perfusion, are presented as to how they facilitate
      accurate determination of plaque constituents underlying biomechanics. Second,
      imaging technologies including hardware and sequences, are reviewed as to how
      they provide the resolution and signal-to-noise ratio necessary for determining
      plaque structure. Finally, techniques for combining MRI data into an overall
      assessment of plaque biomechanical properties, including wall shear stress and
      internal plaque strain, are presented. The paper closes with a discussion of the
      extent to which these techniques have been applied to different arteries commonly
      targeted by vessel wall MRI.

PMID- 20805735
TI  - Molecular imaging with targeted contrast agents.
AB  - Molecular imaging with targeted contrast agents by magnetic resonance imaging
      (MRI) allows for the noninvasive detection and characterization of biological
      changes on a molecular level. In this article, the principles of molecular MRI
      and its applications in cardiovascular diseases are reviewed. First, basic
      properties of positive and negative contrast agents are introduced and their
      effect on signal generation in a magnetic field is described. In the next part,
      different types of MRI scanners and the influence of field strength on signal
      properties of contrast agents for molecular imaging are discussed. Additionally,
      the assessment, analysis, and quantification of the changes in T1 and T2*
      relaxation time induced by the different molecular contrast agents are reviewed.
      Finally, the basic mechanisms of targeting of imaging probes on a molecular level
      and recent applications of molecular MRI in cardiovascular disease are reviewed.

PMID- 20805734
TI  - Multicenter epidemiological studies of atherosclerosis imaging.
AB  - Cardiovascular disease is the leading course of death and disability.
      Conventional cardiac risk factors do not fully explain the level of
      cardiovascular risk, incidence of coronary artery disease, and coronary events.
      Risk stratification and therapy based solely on these conventional risk factors
      may overlook a population who would benefit from lifestyle and risk factor
      modification. Thus, research has recently focused on improving risk assessment
      with new tools in an effort to better identify subjects at highest risk and in
      need of aggressive management. Cardiovascular imaging, both in coronary and
      extracoronary arterial beds, has proven to be very helpful in this regard. In
      this article, we review the current literature from multicenter epidemiology
      studies on the utility of noninvasive imaging modalities for risk stratification
      in the context of conventional risk factor evaluation.

PMID- 20805736
TI  - Analysis of seed loss and pulmonary seed migration in patients treated with
      virtual needle guidance and robotic seed delivery.
AB  - PURPOSE AND BACKGROUND: To determine whether automated seed delivery system and
      real-time intraoperative (IO) virtual needle guidance reduce seed loss and
      pulmonary seed migration. PATIENTS AND METHODS: We analyzed 279 patients with low
      and intermediate risk prostate cancer treated in our institution with radioactive
      iodine (I-125) permanent seed implants. Loose seeds were exclusively used. To
      account for lost seeds, pelvic fluoroscopic imaging from 3 different angles was
      done 30 days after the implant. Posteroanterior and lateral chest x-rays were
      done when seed loss was confirmed. Patients were compared using the chi(2) test
      and Fisher exact test. RESULTS: At least 1 seed was lost in 31.5% of patients
      with a migration rate of 1.02%; 9.3% of patients had at least 1 seed in the lung
      with a migration rate of 0.22%. The population was divided into 3 groups
      according to the order in which they were treated. Seed loss (P=0.02) and
      pulmonary seed embolization (P=0.008) were significantly lower in the second
      hundred than in the first hundred patients. No difference was noted between
      groups 1 and 3 (patient, 201-279). Peri- or extracapsular seed placement was not
      correlated to seed loss (P=0.780 and P=0.092, respectively). No serious
      complications from seed migration were reported. Seed loss did not influence
      dosimetry parameters (V100, V150, and D90). CONCLUSION: Our pulmonary seed
      migration and total seed loss rates are comparable to the ones reported in the
      literature. Virtual needle guidance and automated seed delivery system are in our
      hand as accurate as the manual technique.

PMID- 20805737
TI  - Stereotactic radiotherapy reduces treatment cost while improving overall survival
      and local control over standard fractionated radiation therapy for medically
      inoperable non-small-cell lung cancer.
AB  - PURPOSE: Radiation therapy (RT) is the standard alternative curative treatment
      option for medically inoperable early stage non-small-cell lung cancer (NSCLC).
      Recently, stereotactic body radiotherapy (SBRT) has shown substantial promise to
      improve local control rates as compared with conventional fractionated RT
      [external beam RT (EBRT)]. We compare treatment outcomes and costs between SBRT
      and EBRT in this patient population. MATERIALS AND METHODS: A total of 86
      patients with Stage I (Tl-2 N0) NSCLC were treated with either EBRT (n=41) or
      SBRT (n=45) between January 2002 and April 2008. EBRT patients were treated to a
      median dose of 70 Gy with 3-dimensional conformal RT (n=39) or intensity
      modulated radiation therapy (n=2). SBRT was delivered in 4 or 5 fractions to 48
      (Tl, n=44) or 60 (T2, n=1) Gy. The actual cost was calculated using 2010 Medicare
      hospital-based Ambulatory Payment Classification and hospital-based physician fee
      screen reimbursement rates for both the technical and professional components.
      RESULTS: On the basis of a median number of fractions for this patient
      population, SBRT was significantly less expensive ($13,639 EBRT vs. $10,616 SBRT,
      P < 0.01). Survival analysis demonstrated superior 36-month overall survival
      using SBRT, 71% versus 42% for EBRT (P < 0.05). SBRT also reduced local failure
      by nearly 3 times compared with EBRT (12% vs. 34%, P=0.10). CONCLUSION: In this
      study of Stage I NSCLC patients, SBRT was found to be less expensive than
      standard fractionated EBRT, with the cost savings highly dependent on the number
      of SBRT fractions and EBRT technique (3-dimensional conformal RT vs. intensity
      modulated radiation therapy). SBRT was also associated with superior local
      control and overall survival.

PMID- 20805738
TI  - A comparison of helical tomotherapy to circular collimator-based linear
      accelerator radiosurgery for the treatment of brain metastases.
AB  - PURPOSE: To compare stereotactic radiosurgery treatment plans for the treatment
      of patients with brain metastases generated using Tomotherapy and a circular
      collimator-based SRS approach. MATERIALS AND METHODS: Twenty patients, previously
      treated with circular collimator-based radiosurgery, were replanned using
      Tomotherapy treatment planning software. Tomotherapy planning emphasized dose
      fall off peripheral to the target by allowing for inhomogeneous target coverage.
      Conformity and dose falloff were compared with the circular collimator-based
      plans using the following metrics: prescription isodose to tumor volume ratio,
      conformation number, and homogeneity index to assess effects on targets, whereas
      a combined conformity gradient index and the volume of the 12-Gy isodose volume
      were used to assess differences in dose to normal brain. RESULTS: Although a
      similar homogeneity index was achieved for both sets of plans, plan conformity
      was generally improved using the tomotherapy system whereas dose falloff at the
      target periphery was shallower. The 12-Gy isodose volume increased on average by
      3.4 mL (range, -1.9 to +12.1 mL), for the 20 patients studied, but in spite of
      this, based on modeled predictions, the risk for symptomatic radiation necrosis
      associated with Tomotherapy SRS for each patient still falls within the
      clinically observed ranges for Gamma Knife SRS. CONCLUSION: Tomotherapy can be
      used to create treatment plans that meet the dosimetric and clinical requirements
      for stereotactic radiosurgery.

PMID- 20805739
TI  - Targeting glucose metabolism: an emerging concept for anticancer therapy.
AB  - Mortality from locally advanced and metastatic cancer remains high despite
      advances in our understanding of the molecular basis of the disease and improved
      adjuvant therapies. Recently, there has been an increased interest in cancer
      metabolomics, and in particular, the potential for targeting glucose metabolism,
      for therapeutic gain. This interest stems from the fact that cancer cells
      metabolize glucose very differently from normal cells. Cancer cells
      preferentially switch to aerobic glycolysis rather than oxidative phosphorylation
      as their means of glucose metabolism. This metabolic switch is believed to
      enhance cancer cell survival. Several therapeutic agents that target tumor
      metabolism have shown significant cancer cell cytotoxicity in preclinical
      studies, and some have progressed to clinical trials. In this review, we discuss
      the alteration of carbohydrate metabolism seen in cancer cells, the underlying
      mechanisms, and opportunities for targeting cancer metabolism for therapeutic
      purposes.

PMID- 20805740
TI  - Formation of combined urology and radiation oncology practices: objective data
      from radiation oncologists for rationale.
AB  - OBJECTIVES: We sought to determine motivating factors for radiation oncologists
      to form joint ventures with urologists to provide intensity modulated radiation
      treatment (IMRT) to prostate cancer patients that the urologists diagnose.
      METHODS: The American College of Radiation Oncology developed a survey and
      requested responses from radiation oncologists who had professional relationships
      with urologists to deliver prostate cancer intensity modulated radiation
      treatment in a combined practice. Daily patient treatment totals and practice
      characteristics were queried. To date, there is no actual data to elucidate the
      motivation of radiation oncologists to form such an association. RESULTS: All 75
      respondents indicated that their practice model was a multispecialty group, in
      which the radiation oncologist has an employment agreement to receive the
      professional component for radiation treatment services, and was also a financial
      partner in the technical component. All respondents were economically displaced
      in a geographic region by existing radiation oncology groups, hospital-based
      radiation oncology practice, or both. All radiation oncologist respondents stated
      that they were unable to achieve professional partnership status within a
      radiation oncology group, and 98.6% were unable to obtain a share of the
      technical component for radiation treatment. Eighty-six percent of respondents
      treated patients with nonprostate malignancies in their facility, at a rate of
      1.9 times more nonprostate patients than prostate patients. CONCLUSION: This data
      may indicate that radiation oncologists combine with urologists in a geographic
      area where the radiation oncologist has been economically displaced, has existing
      referral patterns, and continues to treat other patients with nonprostate
      malignancies.

PMID- 20805741
TI  - Long-term results of a randomized trial on the sequencing of radiotherapy and
      chemotherapy in breast cancer.
AB  - OBJECTIVE: A prospective, phase III randomized study was undertaken to compare
      the outcomes of 2 different radiotherapy and chemotherapy sequences in
      conservatively treated patients with breast cancer. METHODS: Between January 1997
      and November 2002, 206 patients operated of quadrantectomy and axillary
      dissection for breast cancer, candidates to receive adjuvant CMF chemotherapy
      (cyclophosphamide, methotrexate, and fluorouracil) were assigned to concurrent or
      sequential radiation treatment by using a balanced randomization method. Before
      randomization patients were stratified by tumor diameter, age, and lymph node
      status. The primary end point was the freedom from breast recurrence, and
      secondary end points were overall and disease-free survival. Overall outcomes
      were analyzed according to the intention-to-treat principle. RESULTS: All 206
      patients enrolled and randomized in the trial were analyzed. The median follow-up
      was 111 months, with no patient lost for follow-up. No difference in 10-years
      breast recurrence-free, disease-free, metastasis-free, and overall survival rates
      was observed in the 2 treatment sequence groups. The Hazard Ratios, calculated
      for each prognostic factor, showed no difference in all outcomes between the 2
      treatment sequences. CONCLUSIONS: No influence of the treatment sequence on long
      term outcomes was observed in this trial. This finding suggests that to avoid an
      increased risk of distant recurrence or an excessive toxicity, radiation therapy
      may be delayed until after the end of the more, recently used, anthracycline
      based chemotherapy without increasing the risk of breast recurrences, thus
      allowing the delivery of full-dose chemotherapy in patients at risk for systemic
      disease spread.

PMID- 20805742
TI  - Locoregional recurrence in patients with triple-negative breast cancer:
      preliminary results of a single institution study.
AB  - PURPOSE: To examine the impact of radiotherapy on breast cancer patients with
      triple-negative (ER-, PR-, HER2/neu-) disease. MATERIALS AND METHODS: A
      prospectively collected database of 152 triple negative breast cancer patients
      was initiated in 2004. A total of 77 patients who had all phases of their therapy
      (surgery, chemotherapy, and radiotherapy) at our institution with a minimum of 2
      months follow-up are included. Patients with all types of surgery (lumpectomy or
      mastectomy), chemotherapy (neoadjuvant or adjuvant), and radiotherapy (tangents
      only or comprehensive nodal irradiation) are included. Patients received
      radiotherapy in the setting of breast-conservation and in the postmastectomy
      setting for >=5 cm primary tumors and/or >=4 positive lymph nodes. Patients were
      divided into 2 groups for statistical analysis, based on whether they received
      radiotherapy or not. RESULTS: In the cohort, 53 (69%) received radiotherapy, 24
      (31%) received no radiotherapy. The median follow-up was 23.2 months (range, 2.0
      63.1). In the alive patients, the median follow-up time was 25.6 (range, 2.0
      63.1) months. Patients who received radiotherapy were significantly more likely
      to be of a higher AJCC stage (P < 0.001) than patients who did not receive
      radiotherapy. Of the patients who received radiotherapy, 33 (61.1%) did so for
      breast conservation. For the entire group, 1- and 3-year overall survivals are
      90.9% and 86.3%, respectively. The 3-year actuarial locoregional relapse-free
      survival probability for patients who received radiation was higher than those
      who did not receive radiation (79.6% vs. 57.9%, P = 0.049). CONCLUSIONS: Despite
      significantly lower AJCC stage, patients with triple-negative breast cancer who
      do not undergo radiotherapy have a significantly higher risk of locoregional
      recurrence.

PMID- 20805743
TI  - Is there a role of ACP1-ADA1 genetic complex in immune reaction? Association with
      T1D and with past malarial morbidity.
AB  - In this article, we confirm the positive association of acid phosphatase locus 1
      (ACP1)*A/adenosine deaminase locus 1 (ADA1)*2 gametic type with type 1 diabetes
      (T1D) previously reported and show a negative correlation between the frequency
      of this gametic type with past malarial morbidity in Sardinia. One hundred seven
      adult women with T1D and 385 healthy adult women from the Caucasian population of
      Central Italy have been studied. Data on 1384 children from the central area of
      Sardinia have also been reexamined. T1D subjects show a highly significant
      increase of ACP1*A/ADA1*2 gametic type compared with healthy subjects from the
      same population (P = 0.003). The frequency of ACP1*A/ADA1*2 gametic type is
      decreasing with increasing past malarial morbidity. Because ADA1*2 allele
      decreases the activity of *A allele and since low ACP1 activity decreases Zeta
      chain-associated protein kinase with molecular weight 70 kDa (Zap70) activity
      resulting in weak T-cell receptor signalling an epistatic interaction involving
      ADA1, ACP1 and Zap70 seems a likely mechanism for the associations observed.

PMID- 20805744
TI  - The impact of artificial tears containing hydroxypropyl guar on mucous layer.
AB  - PURPOSE: The aim of this study was to investigate the effect of lubricant
      eyedrops containing propylene glycol 400 (PEG) and polyethylene glycol (PG) with
      hydroxypropyl guar (HP-guar) as a gelling agent on the precorneal mucous layer in
      vivo. METHODS: Sixteen New Zealand white rabbits were randomly assigned to 1 of 4
      groups. All rabbits received PEG/PG/HP-guar tear products in the right eye.
      PEG/PG/HP-guar with Polyquad, 0.1% hyaluronate sodium, 0.5%
      carboxymethylcellulose, or phosphate-buffered saline was placed in the left eyes
      of animals in each group. All eyedrops were used 4 times a day for 7 days. An
      additional 8 rabbits were randomly assigned to 1 of 2 groups. One group received
      PEG/PG/HP-guar products 4 times a day for 7 days (long-term exposure group), and
      the other group received PEG/PG/HP-guar products 3 times at 5-minute intervals
      (short-term exposure group). Fifteen minutes after the last drop was
      administered, each cornea was immediately excised and mucous layer thickness
      measured by transmission electron microscopy. RESULTS: Mucous layer thickness was
      significantly greater in eyes treated with PEG/PG/HP-guar products compared with
      those treated with 0.1% hyaluronate sodium, 0.5% carboxymethylcellulose, or
      phosphate-buffered saline (all P values < 0.001). There were no significant
      differences in mucous layer thickness between PEG/PG/HP-guar products and
      PEG/PG/HP-guar with Polyquad or in the long- and short-term exposure animals.
      CONCLUSIONS: This study demonstrates that even a short exposure to PEG/PG/HP-guar
      tear product increased precorneal mucous layer thickness.

PMID- 20805745
TI  - Beta-blockers, calcium channel blockers, angiotensin converting enzyme inhibitors
      and angiotensin receptor blockers: should they be stopped or not before
      ambulatory anaesthesia?
AB  - PURPOSE OF REVIEW: As day surgery continues to expand, more patients will be
      encountered who are chronically taking a range of cardiovascular medications for
      the management of hypertension and ischaemic heart disease. This review will
      consider the available evidence relating to whether or not these medications
      should be continued throughout the perioperative period in ambulatory surgical
      patients. RECENT FINDINGS: There has been relatively little research in this area
      which is specific to ambulatory surgery and much of the available evidence from
      major surgery has been assembled over the many years that these medications have
      been in use. In order to provide a comprehensive and balanced review, we have
      considered relevant evidence outside of the usual review period. SUMMARY:
      Patients should continue to take beta-blockers and calcium channel blockers on
      the day of surgery. Continuing angiotensin converting enzyme (ACE) inhibitors and
      angiotensin receptor blockers increases the likelihood of intraoperative
      hypotension. This can be reduced by withholding these drugs, but will also
      respond to simple treatments without any apparent adverse outcomes. It may
      therefore simplify instructions to patients if they are told to take all cardiac
      medications as normal.

PMID- 20805746
TI  - Assessment of minimal residual disease in acute myeloid leukemia.
AB  - PURPOSE OF REVIEW: The last 15 years have witnessed significant improvements in
      technologies to detect minimal residual disease (MRD) in acute myeloid leukemia
      (AML). We review recent studies highlighting the potential for novel and
      standardized assays to provide independent prognostic information and develop
      more personalized treatment approaches. RECENT FINDINGS: Progress includes
      establishment of optimized real-time quantitative PCR (RQ-PCR) assays for WT1
      (commonly overexpressed and a putative therapeutic target) and mutant NPM1 genes.
      Moreover, sequential MRD monitoring using an internationally standardized PML
      RARA RQ-PCR assay has been successfully used to guide molecularly targeted
      therapy in acute promyelocytic leukemia (APL). There have also been significant
      advances in multiparameter flow cytometry (MFC) to detect MRD, with introduction
      of 6-10 color technology and improved understanding of the immunophenotype of
      leukemic stem cells. SUMMARY: Sensitive MRD detection using MFC and/or RQ-PCR has
      become feasible in virtually all AML patients. MRD monitoring is now considered a
      standard of care in APL. Recent studies provide a strong rationale for
      prospective trials investigating the merits of extending MRD detection to alter
      therapy and potentially improve outcome in other AML subtypes.

PMID- 20805747
TI  - Advances in understanding and management of polycythemia vera.
AB  - PURPOSE OF REVIEW: Polycythemia vera is a relatively common myeloproliferative
      neoplasm (MPN) molecularly defined by the presence of mutations in the janus
      kinase (JAK2) gene. Yet, many aspects of pathogenesis remain to be ascertained
      and no effective treatment for curing the disease or preventing major
      cardiovascular events and progression to myelofibrosis or acute leukemia exists.
      The objective of this report is to review recent advances in the field and
      discuss the potential of novel therapeutic approaches. RECENT FINDINGS: The
      discovery of a specific germline haplotype in JAK2 provided an explanation for
      the well known phenomenon of familial clustering of MPN. Clinical trials with
      JAK2 inhibitors, either specific or not, have been initiated and first results
      are available. However, the expectation that these drugs could selectively target
      mutant cells and cause a molecular remission, similar to the experience with
      imatinib in chronic myelogenous leukemia, has been largely unmet. With the aim to
      develop common tools for clinicians involved in conventional and experimental
      therapies, a set of criteria for evaluating response to treatment have been
      developed. SUMMARY: The last couple of years have witnessed significant
      improvements in understanding polycythemia vera biology and management, and the
      activation or completion of novel trials are expected to provide further
      information to improve the treatment.

PMID- 20805748
TI  - Molecular genetics in acute myeloid leukemia.
AB  - PURPOSE OF REVIEW: Acute myeloid leukemia (AML) is a highly heterogeneous
      disorder being composed of various genetically defined subtypes. In recent years,
      molecular research provided the basis for a more differentiated characterization
      of AML patients, for example, of the large subgroup with normal karyotypes. This
      review summarizes the current status of molecular diagnostics in AML and refers
      to the diagnostic techniques being most suitable for the individual markers.
      RECENT FINDINGS: A molecular data set based on mutations of the NPM1, FLT3, and
      CEBPA genes and the MLL-PTD provides a prognostically relevant risk
      stratification that can support the decision pro or con an allogeneic
      hematopoietic stem cell transplantation in first remission. The panel of known
      molecular markers is continuously increasing, for example, considering the
      recently described TET2 and IDH1 mutations. The introduction of next generation
      sequencing will certainly catalyze the molecular characterization of AML.
      Monitoring of the minimal residual disease load with quantitative real-time PCR
      can be performed for NPM1 and MLL-PTD-mutated cases. SUMMARY: Targeted therapy
      studies with FLT3 inhibitors for patients with FLT3-mutated AML as single agents
      or combined with chemotherapy illustrate the translation of the molecular
      techniques into clinical practice already being realized in distinct subgroups of
      AML.

PMID- 20805749
TI  - Ultrasound pregnancy dating leads to biased perinatal morbidity and neonatal
      mortality among post-term-born girls.
AB  - BACKGROUND: Ultrasound assessment of gestational length is based on the
      assumption that fetuses of the same gestational age have equal size at the time
      of investigation. However, there are detectable sex differences in fetal size by
      the end of the first trimester. We examined whether ultrasound dating introduces
      sex differences in risks of adverse perinatal outcomes related to post-term
      birth. METHODS: We used the Swedish Medical Birth Register to compare male and
      female newborns during 1973-1978, when gestational age was based on the last
      menstrual period, and 1995-2007, when gestational age was based on ultrasound. We
      included singleton births from 39 to 43 gestational weeks. RESULTS: During the
      first time period, the newborn male-to-female ratio by gestational age at
      delivery was constant around 1.0, but in the later time period it consistently
      increased by gestational age, reaching 1.60 at 43 weeks. In the first time
      period, post-term females had reduced risk for adverse perinatal outcomes
      compared with post-term males. After the introduction of ultrasound, post-term
      females had higher risks of stillbirth (odds ratio = 1.60 [95% confidence
      interval = 1.11 to 2.30]) and meconium aspiration (1.39 [1.10 to 1.75]), compared
      with post-term males. One-third of stillbirths among post-term girls today might
      be due to incorrect calculation of gestational age. CONCLUSIONS: Introduction of
      ultrasound for the estimation of gestational age may be associated with increased
      risks of adverse perinatal outcomes among females classified as post-term
      compared with their male counterparts.

PMID- 20805750
TI  - Maternal use of Swedish snuff (snus) and risk of stillbirth.
AB  - BACKGROUND: Swedish snuff has been discussed internationally as a safer
      alternative to tobacco smoking. International cigarette manufacturers are
      promoting new snuff products, and the use of Swedish snuff is increasing,
      especially among women of childbearing age. The effect of Swedish snuff on
      pregnancy complications is unknown. METHODS: In this population-based cohort
      study, we estimated the risk of stillbirth in snuff users (n = 7629), light
      smokers (1-9 cigarettes/day; n = 41,488), and heavy smokers (>=10 cigarettes/day;
      n = 17,014), using nontobacco users (n = 504,531) as reference. RESULTS: Compared
      with nontobacco users, snuff users had an increased risk of stillbirth (adjusted
      odds ratio = 1.6 [95% confidence interval = 1.1-2.3]); the risk was higher for
      preterm (<37 weeks) stillbirth (2.1 [1.3-3.4]). For light smokers, the adjusted
      odds ratio of stillbirth was 1.4 (1.2-1.7) and the corresponding risk for heavy
      smokers was 2.4 (2.0-3.0). When we excluded women with preeclampsia or antenatal
      bleeding and infants who were small for gestational age, the smoking-related
      risks of stillbirth was markedly attenuated; the elevated risk for snuff users
      remained the same level. CONCLUSIONS: Use of Swedish snuff during pregnancy was
      associated with a higher risk of stillbirth. The mechanism behind this increased
      risk seems to differ from the underlying mechanism in smokers. Swedish snuff does
      not appear to be a safe alternative to cigarette smoking during pregnancy.

PMID- 20805751
TI  - Maternal use of acetaminophen, ibuprofen, and acetylsalicylic acid during
      pregnancy and risk of cryptorchidism.
AB  - BACKGROUND: Cyclooxygenase (COX) inhibitors-acetaminophen, ibuprofen and
      acetylsalicylic acid-have endocrine-disruptive properties in the rainbow trout.
      In humans, aspirin blocks the androgen response to human chorionic gonadotropin
      (hCG), and, because hCG-stimulated androgen production in utero is crucial for
      normal testicular descent, exposure to COX inhibitors at vulnerable times during
      gestation may impair testicular descent. We examined whether prenatal exposure to
      acetaminophen, ibuprofen, and acetylsalicylic acid was associated with increased
      occurrence of cryptorchidism. METHODS: Our study used data on 47,400 live-born
      singleton sons of mothers enrolled in the Danish National Birth Cohort during
      1996-2002. Cryptorchidism was identified in 980 boys during childhood, of whom
      565 underwent orchiopexy. The use of acetaminophen, ibuprofen, and
      acetylsalicylic acid during pregnancy was assessed in 3 computer-assisted
      telephone interviews and 1 self-administered questionnaire. We estimated adjusted
      hazard ratios (HRs) of cryptorchidism by Cox regression analysis. RESULTS:
      Exposure to acetaminophen during both the first and second trimesters was
      associated with increased occurrence of cryptorchidism (HR = 1.33 [95% confidence
      interval = 1.00-1.77]). Exposure for more than 4 weeks within the postulated time
      window of programming testicular descent (gestational weeks 8-14) was associated
      with a HR of 1.38 (1.05-1.83) for cryptorchidism. Exposure to ibuprofen and
      acetylsalicylic acid was not associated with cryptorchidism. CONCLUSION: Maternal
      intake of acetaminophen for more than 4 weeks during pregnancy, especially during
      the first and second trimesters, may moderately increase the occurrence of
      cryptorchidism.

PMID- 20805752
TI  - The effective reproduction number of pandemic influenza: prospective estimation.
AB  - BACKGROUND: Timely estimation of the transmissibility of a novel pandemic
      influenza virus was a public health priority in 2009. METHODS: We extended
      methods for prospective estimation of the effective reproduction number (Rt) over
      time in an emerging epidemic to allow for reporting delays and repeated
      importations. We estimated Rt based on case notifications and hospitalizations
      associated with laboratory-confirmed pandemic (H1N1) 2009 virus infections in
      Hong Kong from June through October 2009. RESULTS: Rt declined from around 1.4
      1.5 at the start of the local epidemic to around 1.1-1.2 later in the summer,
      suggesting changes in transmissibility perhaps related to school vacations or
      seasonality. Estimates of Rt based on hospitalizations of confirmed H1N1 cases
      closely matched estimates based on case notifications. CONCLUSION: Real-time
      monitoring of the effective reproduction number is feasible and can provide
      useful information to public health authorities for situational awareness and
      calibration of mitigation strategies.

PMID- 20805753
TI  - Ischemic heart disease and stroke in relation to blood DNA methylation.
AB  - BACKGROUND: Epigenetic features such as DNA hypomethylation have been associated
      with conditions related to cardiovascular risk. We evaluated whether lower blood
      DNA methylation in heavily methylated repetitive sequences predicts the risk of
      ischemic heart disease and stroke. METHODS: We quantified blood DNA methylation
      of Long Interspersed Nucleotide Element-1 (LINE-1) repetitive elements through
      PCR-pyrosequencing in 712 elderly individuals from the Boston-area Normative
      Aging Study. We estimated risk-factor adjusted relative risks (RRs) for ischemic
      heart disease and stroke at baseline (242 prevalent cases), and during follow-up
      (44 new cases; median follow-up, 63 months), as well as subsequent mortality from
      ischemic heart disease (86 deaths; median follow-up, 75 months). RESULTS: Blood
      LINE-1 hypomethylation was associated with baseline ischemic heart disease (RR =
      2.1 [95% confidence interval = 1.2-4.0] for lowest vs. highest methylation
      quartile) and for stroke (2.5 [0.9-7.5]). Among participants free of baseline
      disease, individuals with methylation below the median also had higher risk of
      developing ischemic heart disease (4.0 [1.8-8.9]) or stroke (5.7 [0.8-39.5]). In
      the entire cohort, persons with methylation below the median had higher mortality
      from ischemic heart disease (3.3 [1.3-8.4]) and stroke (2.8 [0.6-14.3]). Total
      mortality was also increased (2.0 [1.2-3.3]). These results were confirmed in
      additional regression models using LINE-1 methylation as a continuous variable.
      CONCLUSIONS: Subjects with prevalent IHD and stroke exhibited lower LINE-1
      methylation. In longitudinal analyses, persons with lower LINE-1 methylation were
      at higher risk for incident ischemic heart disease and stroke, and for total
      mortality.

PMID- 20805754
TI  - Dexmedetomidine versus fentanyl as adjuvant to propofol: comparative study in
      children undergoing extracorporeal shock wave lithotripsy.
AB  - BACKGROUND: the present study was designed to compare the efficacy, tolerability
      and safety of dexmedetomidine and fentanyl when combined with propofol during
      extracorporeal shock wave lithotripsy in children. METHODS: fifty children aged 3
      8 years, the American Society of Anesthesiologists status I and II, scheduled for
      elective extracorporeal shock wave lithotripsy were randomly allocated to receive
      a loading dose 0.7 MUg kg over 10 min followed by maintenance infusion 0.3 MUg kg
      h of either dexmedetomidine in propofol/dexmedetomidine group or fentanyl in
      propofol/fentanyl group (n = 25 each). The target drug infusion rates were
      adjusted to keep the haemodynamics within +/- 20% from the baseline values. All
      patients received propofol infusion to maintain bispectral index values (40-60)
      throughout the procedure. Induction and maintenance doses of propofol were
      recorded. Total doses of both studied drugs were calculated. Perioperative
      haemodynamics, incidence of intraprocedural and postprocedural complications and
      time to first analgesic requirement were recorded. RESULTS: the propofol
      requirement was significantly lower in the propofol/dexmedetomidine group than
      that in propofol/fentanyl group during induction and maintenance of anaesthesia
      (P < 0.0001). Total doses of fentanyl and dexmedetomidine were 0.961 (0.1) MUg kg
      and 0.925 (0.07) MUg kg, respectively. Mean arterial pressure and heart rate were
      significantly decreased compared to the baseline throughout the procedure in both
      groups and increased significantly relative to both baseline and the other group
      at 30 min in the propofol/fentanyl group and 60 min in the
      propofol/dexmedetomidine group in the recovery area (P < 0.05). In
      propofol/dexmedetomidine group, the incidence of intraprocedural hypoventilation
      was significantly lower (P = 0.016) and time to first analgesic requirement was
      significantly longer (P < 0.0001) than that in propofol/fentanyl group.
      CONCLUSION: both propofol/fentanyl and propofol/dexmedetomidine combinations at
      mentioned dose regimen were effective and well tolerated for children undergoing
      extracorporeal shock wave lithotripsy. However, propofol/dexmedetomidine
      combination was accompanied with less propofol consumption, prolonged analgesia
      and lower incidence of intraprocedural and postprocedural complications.

PMID- 20805755
TI  - Cytological screening for cervical cancer in the province of Limburg, Belgium.
AB  - Cervical cancer screening in Belgium is mainly opportunistic with periodic
      attempts to organize it according to the European guidelines. In the province of
      Limburg (north-east Belgium), a cervical cytology registry was set up in
      collaboration with local cytopathological laboratories, provincial health
      authorities and the Limburg Cancer Registry. Laboratories regularly communicated
      coded results of Pap smears from women residents in Limburg to the provincial
      cytological registry. All individual records contained a virtually unique
      identifying code allowing the study of longitudinal histories and linkage with
      the cancer registry. The screening coverage (percentage of women with a Pap smear
      in a defined period), the prevalence and incidence of squamous intraepithelial
      lesions and changes over time and geographical area were evaluated using a
      database of more than 600 000 Pap smear interpretations between 1996 and 2005. In
      2000, 47% of women aged between 25 and 64 years had at least one Pap smear
      recorded in the last 3 years, and the average number of smears screened for each
      woman was 1.5. On account of incomplete registration, the coverage was 8% lower
      than estimated from health insurance data. The modal screening interval was in
      the range of 12-14 months; the first quartile, median and third quartile were
      355, 440 and 676 days, respectively. Over the 10 years, 82% of the target
      population had their Pap smear recorded. The prevalence of cytological
      abnormalities was 3.7% (atypical squamous cells of undetermined significance:
      2.2%, atypical glandular cells of undetermined significance: 0.1%, low-grade
      squamous intraepithelial lesion: 1.1%, high-grade squamous intraepithelial lesion
      or more serious lesions: 0.4%), but varied substantially among laboratories. The
      prevalence of atypical squamous cells of undetermined significance and low-grade
      squamous intraepithelial lesion increased significantly over time. Pathologists
      from Limburg have pioneered cytology registration in the context of opportunistic
      screening in Belgium. The estimated screening coverage was slightly
      underestimated. Obligatory registration, use of a uniform terminology and linkage
      with population and follow-up data are needed to give a cytology registry its
      full role in an organized screening programme.

PMID- 20805756
TI  - Psychometric evaluation of the Snaith-Hamilton pleasure scale in adult
      outpatients with major depressive disorder.
AB  - The inability to experience pleasure, anhedonia, is recognized as a hallmark
      symptom of depression. An instrument developed for the assessment of hedonic
      capacity is the 14-item, self-report, Snaith-Hamilton Pleasure Scale (SHAPS), but
      its psychometric properties have not been adequately evaluated. This study
      examined the reliability and validity of the SHAPS using a large sample of adult
      outpatients with major depressive disorder (MDD). Data for this study were
      obtained from 461 adult outpatients with a diagnosis of MDD who participated in
      Implementation of Algorithms using Computerized Treatment Systems Project.
      Internal consistency of the SHAPS was assessed using the Cronbach's coefficient
      alpha. A principal factor analysis was used to define the dimensionality of the
      SHAPS. Convergent and discriminant validity was assessed by evaluating the
      Pearson correlations between the SHAPS total score and the pleasure/enjoyment
      item of the 30-item Inventory of Depressive Symptomatology - Clinician-rating
      (IDS-C30); Quality of Life, Enjoyment, and Satisfaction Questionnaire; 17-item
      Hamilton Rating Scale for Depression; IDS-C30; 16-item Quick Inventory of
      Depressive Symptomatology; and 10-item clinician-rated Montgomery-Asberg
      Depression Rating Scale, respectively. The internal consistency of the SHAPS was
      0.91. A one-factor solution emerged for the SHAPS (eigen-values of the first two
      initial factors were 5.95 and 0.43, respectively). Pearson correlations revealed
      a positive linear relationship between the SHAPS total score and the total scores
      on the 17-item Hamilton Rating Scale for Depression (r=0.49, P<0.0001), IDS-C30
      (r=0.56, P<0.0001), 16-item Quick Inventory of Depressive Symptomatology (r=0.55,
      P<0.0001), and 10-item clinician-rated Montgomery-Asberg Depression Rating Scale
      (r=0.53, P<0.0001). The SHAPS total score was negatively correlated with the
      Quality of Life, Enjoyment, and Satisfaction Questionnaire (r=-0.65, P<0.0001).
      This study shows that the SHAPS is a reliable, valid, and unidimensional
      instrument used to assess the hedonic capacity in adult outpatients with MDD.

PMID- 20805757
TI  - The recovery of walking in stroke patients: a review.
AB  - We reviewed the literature on walking recovery of stroke patients as it relates
      to the following subjects:epidemiology of walking dysfunction, recovery course of
      walking, and recovery mechanism of walking (neural control of normal walking, the
      evaluation methods for leg motor function, and motor recovery mechanism of
      leg).The recovery of walking is one of the primary goals in stroke patients,
      along with the recovery of hand function and cognition. Walking function has
      greater potential for recovery than hand function because motor function of the
      leg is less dependent on the lateral corticospinal tract than that of hand
      function. This suggests that detailed knowledge of walking can be used to
      increase the likelihood that stroke patients recover their ability to walk.
      Therefore, we suggest that further research should focus on these topics,
      especially, on the neural control mechanism of walking and motor recovery
      mechanisms of the leg in stroke patients.

PMID- 20805758
TI  - Upper limb assessment in tetraplegia: clinical, functional and kinematic
      correlations.
AB  - The aim of this study was to correlate clinical and functional evaluations with
      kinematic variables of upper limp reach-to-grasp movement in patients with
      tetraplegia. Twenty chronic patients were selected to perform reach-to-grasp
      kinematic assessment using a target placed at a distance equal to the arm's
      length. Kinematic variables (hand peak velocity, movement time, percent time-to
      maximal velocity, index of curvature, number of peaks, and joint range of motion)
      were correlated to clinical (Standard Neurological Classification of Spinal Cord
      Injury-American Spinal Injury Association) and functional [Functional
      Independence Measure (FIM) and Spinal Cord Independence Measure II (SCIM II)]
      evaluation scores. Twenty control participants were also selected to obtain
      normal reference parameters. There was a positive correlation between total motor
      index and FIM (r=0.6089; P=0.0044) and SCIM II (r=0.5229; P=0.018). Both
      functional scores showed positive correlation with each other (r=0.8283;
      P<0.0001). A correlation was also observed between the right and left motor
      indices, the motor FIM, and the SCIM II in most of the reach-to-grasp kinematic
      variables studied (hand peak velocity, movement time, index of curvature, and
      number of peaks). In contrast, for the joint range of motion (shoulder, elbow,
      and wrist), only the wrist in the horizontal plane showed correlation with
      clinical variables. This study shows that muscle strength assessed by the
      American Spinal Injury Association motor index influences the reach-to-grasp
      kinematic variables of patients with tetraplegia. However, the functional
      assessments did not present the same influence.

PMID- 20805759
TI  - Small volume 7.5% NaCl with 6% Dextran-70 or 6% and 10% hetastarch are associated
      with arrhythmias and death after 60 minutes of severe hemorrhagic shock in the
      rat in vivo.
AB  - BACKGROUND: Hypertonic saline solutions in combination with colloids may have
      some applications in critically ill patients. Our aim was to examine the effects
      of small volumes (0.7-1 mL/kg intravenous) of 7.5% NaCl with different colloids
      on cardiac stability, hemodynamics, and mortality after severe hemorrhagic shock.
      METHODS: Male fed Sprague-Dawley rats (300-450 g, n = 48) were anesthetized and
      randomly assigned to one of six groups: (1) untreated (bleed only), (2) 7.5%
      NaCl, (3) 7.5% NaCl/6% dextran-70, (4) 7.5% NaCl/6% hetastarch (HES), (5) 6% HES
      alone, and (6) 7.5% NaCl/10% HES. Hemorrhagic shock was induced by phlebotomy
      until the mean arterial pressure (MAP) was 35 mm Hg to 40 mm Hg and continued for
      20 minutes until ~40% blood loss. Animals were left in shock for 60 minutes at 34
      degrees C. 0.3 mL (<4% of shed blood) was injected as a 10 seconds bolus into the
      femoral vein. Lead II electrocardiogram, blood pressures, MAP, and heart rate
      were monitored. RESULTS: Untreated rats were highly arrhythmogenic with 38%
      mortality. 7.5% NaCl increased MAP from 39 mm Hg to 44 mm Hg with no severe
      arrhythmias or mortality. Dextran-70 increased MAP from 38 mm Hg to 49 mm Hg,
      transiently increased QRS amplitude (1.5 times) and was arrhythmogenic affecting
      50% of animals with no deaths. Addition of 6% HES to hypertonic saline resulted
      in aberrant arrhythmias and 38% mortality. Six percent HES alone was
      proarrhythmic and led to 38% mortality. 7.5% NaCl with 10% HES resulted in 100%
      mortality (p < 0.05) from arrhythmias within 5 minutes of resuscitation.
      CONCLUSIONS: Small volumes of 7.5% NaCl led to fewer arrhythmias and a 2.6 times
      survival benefit over untreated rats, and a partial resuscitation of MAP into the
      "permissive range." Dextran-70 or HES in 7.5% NaCl were proarrhythmic and HES led
      to increased mortality (p < 0.05). Because optimal heart function is critical for
      successful resuscitation, care should be exercised when using dextran-70 or 6 and
      10% HES in small volume hypertonic saline solutions for early hypotensive
      resuscitation.

PMID- 20805760
TI  - The effect of intramedullary reaming on a diaphyseal bone defect of the tibia.
AB  - BACKGROUND: The effect of intramedullary reaming on diaphyseal tibial defects has
      not been examined in the literature. The present aim was to relate the extent of
      reaming to angiogenesis and bone formation occurring around a critical-sized
      defect in the tibia for two scenarios, namely, when the bone defect is left empty
      and when the bone defect is treated with autograft. METHODS: Eleven canines were
      allocated into two groups, namely, empty (n=5) or iliac crest autograft (n=6).
      All tibiae were reamed to 7.0 mm and fixed with a 6.5-mm statically locked
      intramedullary nail after creation of an 8.0-mm diaphyseal defect. The extent of
      reaming of the canal was dependent on the cross-sectional area of the tibia,
      because all tibiae were reamed to 7.0 mm. Fluorescent markers were administered
      at different times: calcein green (6 weeks), xylenol orange (9 weeks), and
      tetracycline (11 weeks and 14 weeks). Animals were sacrificed at 15 weeks and
      perfused with a barium compound. Analysis consisted of radiography, micro
      computed tomography scan, and histology. RESULTS: Linear regression analysis of
      percent bone volume and canal area provided a Pearson correlation coefficient of
      r=0.925 (p=0.025) for empty samples and r=0.244 (p=0.641) for autograft samples.
      Linear regression analysis of percent vasculature volume and canal area provided
      a Pearson correlation coefficient of r=0.784 (p=0.117) for empty samples and r=
      0.146 (p=0.783) for autograft samples. Bone formation rates were reported as the
      distance between the fluorescent labels and were less within the endosteum,
      cortex, and periosteum, with extensive reaming in empty samples. CONCLUSIONS: The
      results suggest that limited reaming may be beneficial to the acute management of
      tibial shaft fractures with a bone defect.

PMID- 20805761
TI  - Burn Specific Health up to 24 months after the Burn-A prospective validation of
      the simplified model of the Burn Specific Health Scale-Brief.
AB  - BACKGROUND: Outcome after burn injury is a multidimensional concept, but few
      multidimensional, injury-specific outcome measures have been psychometrically
      evaluated. A recent cross-sectional study using the Burn Specific Health Scale
      Brief (BSHS-B) found three psychometrically sound health domains: function, skin
      involvement, and affect and relations. The aim of this study was to reexamine the
      psychometric properties of the BSHS-B using a prospective study design. METHODS:
      Ninety-four consecutive adult patients with burns were included and asked to fill
      in questionnaires, the BSHS-B, the Hospital Anxiety and Depression Scale, and the
      short-form 36 (SF-36), at 6 months, 12 months, and 24 months postburn. RESULTS:
      The factor structure was replicated and the three domains, function, skin
      involvement, and affect and relations, had excellent internal consistency. Over
      time the scores of function and skin involvement increased, indicating health
      improvement, whereas the domain affect and relations did not change over time. At
      6 months and 12 months postburn, all domains were associated with burn severity.
      The function domain was highly associated with the SF-36 subscales physical
      functioning and role-physical, the affect and relations domain was highly
      associated with the Hospital Anxiety and Depression Scale and the SF-36 subscales
      denoting psychological health, and the domain skin involvement was highly
      associated with subscales indicating role-concerns, social functioning, vitality,
      and mental health. CONCLUSION: The psychometric properties of the BSHS-B domains
      were excellent and they had intelligible concurrent associations with other
      measures. Thus, the simplified model of the BSHS-B is a reliable, valid, and
      useful tool in describing postburn health over time.

PMID- 20805762
TI  - Hydroxyapatite-coated pins versus titanium alloy pins in external fixation at the
      wrist: a controlled cohort study.
AB  - BACKGROUND: The purpose of this study was to analyze whether the prevalence of
      pin-related complications can be reduced by the use of hydroxyapatite (HA)-coated
      pins in external fixators applied for unstable wrist fractures. METHODS: Forty
      patients (160 pins) were randomized for standard uniplanar fixator treatment with
      the use of identically designed pins either composed of titanium-alloy (Ti6Al4V)
      (n = 20) or coated by HA (n = 20). Each pin site was clinically evaluated with
      regard to erythema, drainage, pain value, and radiologically assessed concerning
      loosening at T1 (mean, 9 days), T2 (mean, 43 days), and T3 (mean, 56 days). In
      case of pin-track complication, the patient was followed continuously. The need
      for antibiotics or additional surgery was documented. Bone mineral density was
      analyzed by Dual Energy X-ray Absorptiometry. At fixator removal (T2), the pin
      extraction strength was measured by the use of a digital-torque-wrench. RESULTS:
      Two minor pin-track infections requiring oral antibiotics occurred in the HA-pin
      group (2.7%) (p > 0.05). The vast majority of clinical pin-site parameters were
      comparable in both groups. At the end of the fixator therapy, there were 16 loose
      pins (n(Ti6AL4V-group) = 10; n(HA-group) = 6). The rate of loose pins was
      correlated to patient's age (p < 0.05) but not to bone mineral density values or
      the occurrence of pin-site infection. Finally, no significant difference between
      the two groups was detected with regard to the prevalence of clinical relevant
      pin-site complications (p = 0.80). CONCLUSIONS: In external fixation of the
      wrist, the use of HA-coated pins yields no clinical advantages: there is a trend
      toward a superior pin-bone anchorage, but a tendency of increased susceptibility
      for minor pin-track infections.

PMID- 20805764
TI  - Acute respiratory distress syndrome: performance of ventilator at simulated
      altitude.
AB  - BACKGROUND: Ventilation of Acute Respiratory Distress Syndrome (ARDS) is a
      challenge, and there is definitely a need for lack of variations between
      delivered and set tidal volume (Vt). We have assessed the ability of the
      ventilator T-birdVS02 and LTV-1000 to deliver to a lung model with ARDS a set Vt
      at different simulated altitudes. METHODS: We used a decompression chamber to
      mimic the hypobaric environment at a range of simulated cabin altitudes of 1,500,
      2,500, and 3,000 m (4,000, 6,670, and 8,000 feet, respectively). Ventilators were
      tested with realistic parameters. Vt was set at 400 mL and 250 mL in an ARDS lung
      model. Comparisons of preset to actual measured values were accomplished using a
      t test for each altitude. RESULTS: The T-birdVS02 showed a decrease in the volume
      delivered. Comparisons of actual delivered Vt and set Vt demonstrated a
      significant difference starting at 1,500 m for a Vt set of 400 mL and at 2,500 m
      for Vt set of 250 mL. At these altitudes, the variations between Vt set and
      delivered were more than 10%. With decreasing barometric pressure, the LTV-1000
      showed mostly an increase in volume delivered. Comparisons of actual delivered Vt
      and set Vt demonstrated a significant difference at 2,500 m for a Vt set of 400
      mL and at 3,000 m for Vt set of 250 mL. The delivered Vt remained within 10% of
      the set Vt. CONCLUSION: Clinicians involved in aerial evacuations must keep in
      mind the performance and limitations of their ventilator system.

PMID- 20805763
TI  - Carbachol alleviates rat cytokine release and organ dysfunction induced by
      lipopolysaccharide.
AB  - BACKGROUND: To observe the influence of carbachol on inflammatory cytokine
      release and its protective role on organ function in rat endotoxemia model, and,
      furthermore, to investigate its receptor mechanism in rat peritoneal macrophages
      in vitro. METHODS: In the animal experiments, Wistar rats were subjected to
      lipopolysaccharide (LPS) injection (5 mg/kg body weight) to establish an
      endotoxemia animal model, and carbachol/nicotine was given 15 minutes after LPS
      injection. Serum contents of tumor necrosis factor (TNF)-alpha, interleukin (IL)
      6, and IL-10 were determined with enzyme-linked immunosorbent assay 4 hours after
      LPS injection. Plasma alanine aminotransferase, creatine kinase-MB, and diamine
      oxidase contents were detected 24 hours after LPS injection. In cell experiments,
      rat peritoneal macrophages were collected and initially pretreated with atropine
      (muscarinic cholinergic receptor antagonist) or alpha-Bungarotoxin (an antagonist
      that specifically binds alpha7 subunit of nicotinic cholinergic receptor), then
      with carbachol or nicotine, and finally stimulated with LPS. Contents of TNF
      alpha, IL-6, and IL-10 in supernatant were assayed by enzyme-linked immunosorbent
      assay. Furthermore, macrophages were exposed to nicotine and carbachol of high
      concentration and then stained with fluorescein isothiocyanate-labeled alpha
      bungarotoxin and observed with fluorescent confocal microscopy. RESULTS:
      Carbachol inhibited expression of TNF-alpha and IL-6 after LPS injection and had
      no significant effect on IL-10 in rat endotoxemia model. It also inhibited the
      increase of plasma alanine aminotransferase and creatine kinase-MB contents
      whereas restored the inhibited plasma diamine oxidase activity. Cell experiments
      also showed that increases of TNF-alpha and IL-6 after LPS stimulation could be
      significantly inhibited by carbachol or nicotine, whereas IL-10 was not
      apparently altered. Atropine did not downregulate the inhibitive effects of both
      carbachol and nicotine, whereas alpha-bungarotoxin significantly downregulated
      these effects. Fluorescent confocal microscopy showed that nicotine and carbachol
      pretreatment markedly reduced the intensity of binding between fluorescein
      isothiocyanate-labeled alpha-bungarotoxin and macrophages. CONCLUSION: The
      results suggested that both carbachol and nicotine play a role in the anti
      inflammatory process and organ function protection through the alpha7 subunit of
      nicotinic cholinergic receptor.

PMID- 20805765
TI  - Identification of low-risk patients with traumatic brain injury and intracranial
      hemorrhage who do not need intensive care unit admission.
AB  - BACKGROUND: Patients with traumatic brain injury (TBI) and traumatic intracranial
      hemorrhage are frequently admitted to the intensive care unit (ICU) but never
      require critical care interventions. Improved ICU triage in this patient
      population can improve resource utilization and decrease health care costs. We
      sought to identify a low-risk group of patients with TBI who do not require
      admission to an ICU. METHODS: This is a retrospective cohort study of adult
      patients with TBI and traumatic intracranial hemorrhage. The need for ICU
      admission was defined as the presence of a critical care intervention. Patients
      were considered low risk if there was no critical care intervention before
      hospital admission. Measured outcomes included delayed critical care
      interventions at 48 hours and during hospitalization, mortality, and emergency
      surgery. RESULTS: A total of 187 of 320 patients were considered low risk. In the
      low-risk group, two patients (1.1%; 95% confidence interval [CI], 0.1-3.8) had a
      delayed critical care intervention within 48 hours of admission and four patients
      (2.1%; 95% CI, 0.6-5.4) after 48 hours of admission. Two patients (1.1%; 95% CI,
      0-3.8) in the low-risk group died. No patients in the low-risk group required
      neurosurgical intervention. CONCLUSION: Patients with TBI without a critical care
      intervention before admission are at low risk for requiring future critical care
      interventions. Future studies are required to validate if this low-risk criteria
      can serve as a safe, cost-effective triage tool for ICU admission.

PMID- 20805766
TI  - Tumor necrosis factor alpha gene polymorphism is associated with the outcome of
      trauma patients in Chinese Han population.
AB  - BACKGROUND: Tumor necrosis factor (TNF) is a proinflammatory cytokine that plays
      a major role in the sepsis and multiple organ dysfunction secondary to major
      trauma. The purpose of this article was to research the clinical relevance of the
      TNF gene polymorphism in patients with major trauma. METHODS: Three hundred six
      patients with major trauma were prospectively recruited. The TNF gene
      polymorphisms were genotyped using restriction fragment length polymorphism
      analysis. Plasma TNF-alpha levels were determined with enzyme-linked
      immunosorbent assay. Sepsis morbidity rate and multiple organ dysfunction scores
      were accessed. RESULTS: The TNF-alpha/-308 polymorphism was shown to be well
      associated with increased capacity of peripheral leukocytes to produce TNF-alpha
      in response to ex vivo lipopolysaccharide stimulation in trauma patients at
      admission. Results from association study indicated that trauma patients carrying
      the TNF-alpha/-308/A allele were more likely complicated with sepsis.
      CONCLUSIONS: The TNF-alpha/-308 polymorphism might be used as a biomarker for the
      assessment of outcome of trauma patients, but the TNF-beta/252 gene polymorphism
      might not influence the development of complications in patients with major
      trauma.

PMID- 20805767
TI  - External validation of a prognostic model for early mortality after traumatic
      brain injury.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a major cause of lost disability
      adjusted life years, and a valid model allowing prediction of outcome would be
      welcome. For a clinical prediction model to be valid, generalization to other
      populations must be possible. The aim of this study was to externally validate a
      model for in-hospital mortality in patients with TBI, which was recently
      development at the University of Southern California (USC). METHODS: The
      validation cohort was derived from a hospital-based, prospectively collected
      trauma registry in Oslo, Norway. We included patients admitted with a head injury
      without hypotension, severe thoracic, or abdominal injury (n = 3,136). We
      calculated the probability of death according to the USC model. The performance
      of the model was evaluated using measures of calibration and discrimination in
      the total sample and subgroups according to initial Glasgow Coma Scale (GCS)
      score. RESULTS: The USC model provided excellent discrimination (area under the
      receiver operating characteristic curve, AUC = 0.93), but unsatisfactory
      calibration (p < 0.001) for the total sample (GCS 3-15). In the GCS 4-8 subgroup
      we found good discrimination (AUC = 0.89) but poor calibration (Hosmer-Lemeshow
      test, p < 0.001). CONCLUSION: The findings question the external validity of the
      USC model, suggesting that it should not be implemented as a tool for short-term
      mortality prediction in our TBI population.

PMID- 20805768
TI  - Influence of low-dose nicotine on bone healing.
AB  - BACKGROUND: Nicotine at a low concentration was suggested as a new topical drug
      for clinical application. It has been reported to be capable of enhancing skin
      wound healing. This study was designed to assess the effect of nicotine
      administration at a low dose on bone regeneration using a rabbit model of
      mandibular distraction osteogenesis. METHODS: Twenty New Zealand white rabbits
      were randomly assigned to nicotine group and control group. A total of 0.75 g, 60
      day time release, nicotine pellets or placebos were implanted in the neck
      subcutaneous tissue of the rabbits. The nicotine or placebo exposure time for all
      the animals was 7 weeks. Unilateral mandibular distraction osteogenesis was
      performed. Five animals in each group were killed on week 2 and week 4 of
      consolidation, respectively. The mandibular samples were subjected to
      radiographic, histologic, and immunohistochemical analysis. RESULTS: Nicotine at
      low dose showed no significant effect on the expression of bone morphogenetic
      protein-2 and on the radiodensity of bone regeneration. However, the delayed bone
      healing was detected in the nicotine group by histologic examination.
      CONCLUSIONS: These findings imply a potential risk of compromised bone healing in
      patients taking nicotine medication. Further clinical studies are necessary to
      assess the risk of nicotine medication on reconstructive surgery.

PMID- 20805769
TI  - Diagnostic radiation exposure in pediatric trauma patients.
AB  - BACKGROUND: The amount of imaging studies performed for disease diagnosis has
      been rapidly increasing. We examined the amount of radiation exposure that
      pediatric trauma patients receive because they are an at-risk population. Our
      hypothesis was that pediatric trauma patients are exposed to high levels of
      radiation during a single hospital visit. METHODS: Retrospective review of
      children who presented to Johns Hopkins Pediatric Trauma Center from July 1,
      2004, to June 30, 2005. Radiographic studies were recorded for each patient and
      doses were calculated to give a total effective dose of radiation. All
      radiographic studies that each child received during evaluation, including any
      associated hospital admission, were included. RESULTS: A total of 945 children
      were evaluated during the study year. A total of 719 children were included in
      the analysis. Mean age was 7.8 (+/-4.6) years. Four thousand six hundred three
      radiographic studies were performed; 1,457 were computed tomography (CT) studies
      (31.7%). Average radiation dose was 12.8 (+/-12) mSv. We found that while CT
      accounted for only 31.7% of the radiologic studies performed, it accounted for
      91% of the total radiation dose. Mean dose for admitted children was 17.9 (+/
      13.8) mSv. Mean dose for discharged children was 8.4 (+/-7.8) mSv (p<0.0001).
      Burn injuries had the lowest radiation dose [1.2 (+/-2.6) mSv], whereas motor
      vehicle collision victims had the highest dose [18.8 (+/-14.7) mSv]. CONCLUSION:
      When the use of radiologic imaging is considered essential, cumulative radiation
      exposure can be high. In young children with relatively long life spans, the
      benefit of each imaging study and the cumulative radiation dose should be weighed
      against the long-term risks of increased exposure.

PMID- 20805770
TI  - ScvO(2) as a marker to define fluid responsiveness.
AB  - BACKGROUND: Definition of the hemodynamic response to volume expansion (VE) could
      be useful in shocked critically ill patients in absence of cardiac index (CI)
      measurements. The aim of this study is to evaluate whether central venous oxygen
      saturation variations (DeltaScvO(2)) after VE could be an alternative to classify
      responders (R) and nonresponders (NR) to volume therapy. METHODS: A total of 30
      patients requiring VE were included in this prospective cohort study, all
      equipped with radial arterial line and pulmonary artery catheters. CI, mixed
      venous oxygen saturation (SvO(2)) and ScvO(2) were measured before and after VE.
      CI, SvO(2), and ScvO(2) changes after volume were analyzed using linear
      regression. Receiver operating characteristics curve analysis was used to test
      their ability to distinguish R and NR. RESULTS: DeltaScvO(2) and SvO(2)
      variations after VE (DeltaSvO(2)) were significantly correlated with CI changes
      (DeltaCI) after VE (r = 0.67 and r = 0.49, p < 0.001, respectively). A
      DeltaScvO(2) threshold value of 4% allowed the definition of R and NR patients
      with 86% sensitivity (95%CI; 57-98%) and 81% specificity (95%CI; 54-96%).
      CONCLUSIONS: ScvO2 variations after VE was able to categorize VE efficiently and
      could be suggested as an alternative marker to define fluid responsiveness in
      absence of invasive CI measurement.

PMID- 20805771
TI  - The depiction of protective eyewear use in popular television programs.
AB  - BACKGROUND: Media portrayal of health related activities may influence health
      related behaviors in adult and pediatric populations. This study characterizes
      the depiction of protective eyewear use in the scripted television programs most
      viewed by the age group that sustains the largest proportion of eye injuries.
      METHODS: Viewership ratings data were acquired to assemble a list of the 24 most
      watched scripted network broadcast programs for the 13-year-old to 45-year-old
      age group. The six highest average viewership programs that met the exclusion
      criteria were selected for analysis. RESULTS: Review of 30 episodes revealed a
      total of 258 exposure scenes in which an individual was engaged in an activity
      requiring eye protection (mean, 8.3 exposure scenes per episode; median, 5
      exposure scenes per episode). Overall, 66 (26%) of exposure scenes depicted the
      use of any eye protection, while only 32 (12%) of exposure scenes depicted the
      use of adequate eye protection. No incidences of eye injuries or infectious
      exposures were depicted within the exposure scenes in the study set. CONCLUSION:
      The depiction of adequate protective eyewear use during eye-risk activities is
      rare in network scripted broadcast programs. Healthcare professionals and health
      advocacy groups should continue to work to improve public education about eye
      injury risks and prevention; these efforts could include working with the
      television industry to improve the accuracy of the depiction of eye injuries and
      the proper protective eyewear used for prevention of injuries in scripted
      programming. Future studies are needed to examine the relationship between media
      depiction of eye protection use and viewer compliance rates.

PMID- 20805772
TI  - The relationship between INR and development of hemorrhage with placement of
      ventriculostomy.
AB  - BACKGROUND: This study seeks to evaluate the relationship between the risk of
      symptomatic hemorrhage from ventriculostomy placement and International
      Normalized Ratio (INR) in patients who received a ventriculostomy after traumatic
      brain injury. METHODS: Patients who received a ventriculostomy after traumatic
      brain injury between June 2007 and July 2008 were identified and their medical
      records were abstracted for information. RESULTS: At the time of ventriculostomy
      placement, 32 patients had an INR<1.2, 26 patients had an INR 1.2 to 1.4, 12
      patients had an INR 1.4 to 1.6, and one patient had an INR>1.6 (INR=1.61). No
      significant difference in the risk of hemorrhage between the groups was observed:
      9.4%, 3.9%, 8.3%, and 0%, respectively (p=0.73). In a subgroup analysis of
      patients who received ventriculostomy in the Neurosurgical Intensive Care Unit
      within 24 hours of admission (n=54), the average time between admission and
      ventriculostomy placement in patients who did not receive fresh frozen plasma was
      6.8 hours compared with 9.3 hours (p=0.03) for those who did. CONCLUSIONS: In
      this retrospective study, INRs between 1.2 and 1.6 appeared to be acceptable for
      a neurosurgeon to place an emergent ventriculostomy in a patient with traumatic
      brain injury.

PMID- 20805773
TI  - Cardiac systolic function recovery after hemorrhage determines survivability
      during shock.
AB  - BACKGROUND: Small animal model has not been available to study cardiac
      pathophysiology during hemorrhagic shock. The main purpose of this study,
      therefore, was to establish earlier differences in left ventricle functional
      disturbances during hypovolemia comparable in survival and nonsurvival animals.
      Ventricular pressure-volume relationships have become well established as the
      most rigorous and comprehensive venue to assess intact heart function. METHODS:
      Studies were performed in anesthetized hamsters subjected to a 40% of blood
      volume hemorrhage to induce the hypovolemic shock. A miniaturized conductance
      catheter was used to measure left ventricular pressure and volume. Derived from
      the pressure-volume measurements, cardiac performance was evaluated using
      systolic and diastolic function indices. RESULTS: Thirteen animals were included;
      all animals survived the hemorrhage. Survival rate after 30 minutes of
      hypovolemic shock was 61.5%. End-systolic pressure was improved at the late stage
      of shock in the survival group, whereas no change of this index was found in the
      nonsurvival group. No significant differences in end-diastolic pressure and
      relaxation time constant were found between the nonsurvival and the survival
      groups. Fifteen minutes after the hemorrhage, the stroke work per stroke volume
      ratio significantly improved in the survival compared with nonsurvival, which
      also restored blood pressure. CONCLUSION: The unique advantage of the pressure
      volume methodology over all other available approaches to measure cardiac
      function is that it enables more specific measurement of the left ventricle
      performance independently from loading conditions and heart rate. Our findings
      demonstrated that failure to recover cardiac systolic function after hemorrhage,
      is a major determinant of mortality during hypovolemic shock.

PMID- 20805775
TI  - Airway scope laryngoscopy under manual inline stabilization and cervical collar
      immobilization: a crossover in vivo cinefluoroscopic study.
AB  - BACKGROUND: Direct laryngoscopy along with manual inline stabilization (MIS) is
      currently the standard care for patients with suspected neck injuries. However,
      cervical collar immobilization is more commonly performed in the prehospital
      environment, and its early removal is necessary before intubation. We
      hypothesized that if usability of Airway Scope (AWS) in a difficult airway could
      also bring merits to intubation under cervical collar immobilization, unnecessary
      risk caused by the removal of a neck collar may be prevented. METHODS: In this
      crossover study, 30 consenting patients presenting for surgery were assigned to
      undergo intubation using AWS. Neck was stabilized manually and by a neck collar
      in a random order before laryngoscopy was performed by the same anesthesiologist.
      Measurements include interincisor distance (IID), success rate, intubation time,
      and fluoroscopic examination of the upper and middle cervical spine. RESULTS: IID
      was notably narrower after application of a neck collar (mean +/- SE: MIS, 19 mm
      +/- 1 mm; collar, 10 mm +/- 1 mm; p < 0.01). One and 9 failures were encountered
      in MIS and collar groups, respectively (p = 0.012). Intubation time proved no
      statistical significance. Extension of craniocervical junction was observed in
      both groups, but occipitoatlantal joint was significantly more extended in collar
      group (median [range]: AWS, 10-degree angle [-1 to 20-degree angle]; collar, 14
      degree angle [5 to 26-degree angle]; p < 0.01). DISCUSSION: AWS laryngoscopy
      under cervical collar immobilization fails to meet our expectation. Intubation
      failed in 30% of the cases in collar group whereas only 3.3% of the cases in MIS
      group. Significant difference of mouth opening limitation is probably the major
      reason, as 7 of 9 failed cases in collar group had IID <10 mm. This was
      insufficient to insert the 18-mm blade of AWS. In addition, occipitoatlantal
      joint suffered a greater extension when wearing a neck collar. Differences in the
      method to stabilize the neck may be the reason. CONCLUSION: When compared with
      cervical collar immobilization, AWS laryngoscopy along with MIS seems to be a
      safer and more definite method to secure airway of neck-injured trauma patients
      because it limits less mouth opening and upper cervical spine movement.

PMID- 20805776
TI  - Unstable cervical spine fracture after penetrating neck injury: a rare entity in
      an analysis of 1,069 patients.
AB  - BACKGROUND: The value of cervical spine immobilization after penetrating trauma
      to the neck is the subject of lively debate. The purpose of this study was to
      review the epidemiology of unstable cervical spine injuries (CSI) after
      penetrating neck trauma in a large cohort of patients. METHODS: This is a
      retrospective analysis of patients admitted with penetrating neck injuries to a
      Level I trauma center from January 1996 through December 2008. A penetrating neck
      injury was defined as a gunshot wound (GSW) or stab wound (SW) between the
      clavicles and the base of the skull. Univariate and multivariate analyses were
      performed to investigate associations between injury mechanisms, the presence of
      CSI instability, and mortality. Risk factors independently associated with the
      presence of a CSI were identified. RESULTS: A total of 1,069 patients met
      inclusion criteria, of which 463 patients (43.3%) and 606 patients (56.7%) were
      sustaining GSW and SW, respectively. Overall, 65 patients (6.1%) were diagnosed
      with a CSI with a significantly higher incidence after GSWs compared with SWs
      (12.1% vs. 1.5%; p < 0.001). In four patients (0.4%), the CSI was considered
      unstable, all of them following GSW. All patients with unstable CSI had obvious
      neurologic deficits or altered mental status at the time of admission. Risk
      factors independently associated with the presence of a CSI were GSW to the neck
      and a Glasgow Coma Scale score <=8 on admission (R = 0.16). CONCLUSION: The
      overall incidence of unstable CSI after penetrating trauma to the neck is
      exceedingly low at 0.4%. Following GSW to the neck, an unstable CSI was noted in
      <1% of patients. After cervical SW, however, no spinal instability was noted
      precluding the need for spinal precautions in these instances.

PMID- 20805777
TI  - Somatic and affective anxiety symptoms and menopausal hot flashes.
AB  - OBJECTIVE: Menopausal hot flashes have been associated with increased scores on
      measures of anxiety. Anxiety measures are typically composed of items measuring
      somatic and affective symptoms. Because hot flash symptoms are similar to
      symptoms of somatic anxiety, we wanted to examine the differential contribution
      of somatic anxiety and affective anxiety to hot flash scores. METHODS: A total of
      80 psychologically well-functioning postmenopausal women aged 50 to 64 years were
      administered the Zung Anxiety Index (ZAI), from which total score, somatic
      anxiety subscale score, and affective anxiety subscale score were calculated. The
      outcome measure was a hot flash score that incorporated both frequency and
      severity based on a 7-day diary. A linear regression analysis examined the
      association between hot flashes and the two anxiety subscales controlling for
      age, education, and sleep quality. RESULTS: Higher score on somatic anxiety was
      significantly associated with higher hot flash score (P = 0.04), whereas the
      association with affective anxiety was not significant (P = 0.80). Higher total
      score on the ZAI was also significantly associated with higher hot flash score (P
      = 0.02). CONCLUSIONS: These results suggest that the positive association between
      higher ZAI scores and hot flashes in recently postmenopausal women may be due to
      the overlap between the somatic manifestation of hot flashes and anxiety symptoms
      rather than to an affective anxiety disturbance. These results have potential
      implications for the care and treatment of postmenopausal women, but replication
      is required in other samples including women at different transition stages of
      menopause and women with psychiatric comorbidities.

PMID- 20805778
TI  - Clinical spectrum of shock in the pediatric emergency department.
AB  - OBJECTIVE: The objective of this study was to describe the clinical spectrum of
      patients presenting with shock or developing shock in a pediatric emergency
      department (ED) during an 8-year period. METHODS: An observational study of all
      pediatric ED patients with shock between September 1998 and September 2006 was
      performed. Trauma activations were excluded. A structured, explicit chart review
      using a standardized abstraction form and case definition was completed by 3
      physicians board certified in pediatric emergency medicine. Interrater
      reliability was monitored. RESULTS: A total of 147 cases of shock were
      identified. Septic shock was the underlying physiology in 57% of cases. A
      pathogen was identified in 45% of these cases. Hypovolemic shock due to
      gastroenteritis, metabolic disease, surgical emergencies, or hemorrhage was the
      cause in 24% of cases. Distributive shock represented 14% of cases. Cardiogenic
      shock contributed to 5% of cases. Patients with septic shock received a mean of
      58 mL/kg of crystalloid or colloid versus 50 mL/kg in patients with other causes.
      Intubation and vasopressor use was required in 41% and 21% of cases,
      respectively. Clinical signs of shock developed in the ED after initially
      presenting without clinical signs of shock in 14% of study subjects. Nearly half
      of these episodes occurred after the administration of antimicrobials or
      performance of a lumbar puncture. Mortality was 6% overall and 5% in septic shock
      patients. CONCLUSIONS: Pediatric ED patients with shock represent a diverse
      population with substantial mortality. Of 147 patients, 21 presented without
      clinical signs of shock and deteriorated to a clinical condition meeting the
      definition of shock during the ED course.

PMID- 20805779
TI  - Detection of occult pneumonia in a pediatric emergency department.
AB  - BACKGROUND: Many children undergo chest radiography (CXR) in their evaluation of
      a febrile illness. Pneumonia without signs of respiratory distress or ausculatory
      findings has been previously described (termed occult pneumonia [OP]). OBJECTIVE:
      The objectives of this study were to determine the incidence of OP among children
      who have CXR performed and to identify clinical predictors of OP. METHODS: A
      prospective observational study of children undergoing CXR for possible pneumonia
      was conducted. Standardized data forms were completed before the CXR. Univariate
      analysis and recursive partitioning were used to identify predictors of OP.
      RESULTS: Of 1866 patients enrolled, 308 had no evidence of respiratory distress
      or lower respiratory tract findings and were studied for OP. Twenty-one patients
      had radiographic OP (6.8%; 95% confidence interval [CI], 4.0%-10.6%). Age, height
      of fever, duration or quality of cough, and pulse oximetry were not associated
      with OP. A decision rule based on fever for 1 day or longer or with a combination
      of fever for less than 1 day but worsening cough identifies patients at greater
      risk for OP (likelihood ratio, 1.47; 95% CI, 1.21-1.77). No patient with fever
      for less than 1 day and without any cough or without worsening cough had
      pneumonia (likelihood ratio, 0.40; 95% CI, 0.19-0.84). CONCLUSIONS: Occult
      pneumonia was identified in 1 of 15 patients undergoing CXR without respiratory
      distress or ausculatory findings. Obtaining a CXR for the detection of OP in
      children without cough and with fever for less than 1 day in duration should be
      discouraged.

PMID- 20805781
TI  - A longitudinal view of resident education in pediatric emergency interhospital
      transport.
AB  - OBJECTIVES: : The focus was to examine the educational structure and curricular
      planning involved in current pediatric emergency interhospital transport teams
      that use resident physicians as members of the team and to compare these current
      results with the findings from 2 previous, similar surveys complete during the
      past 2 decades. METHODS: : A 33-item questionnaire, assessing curricular
      components of the transport experience, was sent to a chief resident at all the
      officially listed nonmilitary pediatric residency program in contiguous United
      States. Comparisons were done for each similar item on all 3 questionnaires.
      RESULTS: : After 3 rounds of mailing and telephone follow-up to nonresponders,
      the overall response rates for the 2006 and 1998 surveys were 81% (n = 156) and
      89% (n = 173), respectively. A similar survey on a smaller sample, published in
      1990, used for comparison, had a response rate of 99% (n = 75). When asked about
      training provided to residents before going on transport, respondents varied in
      the specific experiences and skills required of the residents. In addition,
      programs reported variation in team backup during the pediatric emergency
      transport. The most common method of evaluation for the resident on completion of
      the transport was "no specific method" as reported by 62% of respondents in 2006
      compared with 50% in 1998 and 55% in 1990 (P = not significant). The percentage
      of programs providing informal verbal feedback was reduced significantly in 2006
      as compared with that in 1998 (P = 0.011). CONCLUSIONS: : The educational
      structure for residents serving in pediatric emergency interhospital transport
      teams remains variable, and the full educational value of pediatric transports
      continues to be somewhat unrealized particularly in the area of posttransport
      performance feedback and evaluation. Having medical command available has
      consistently been a strong point of the residents' experience on the transport
      team.

PMID- 20805780
TI  - Extreme stress hyperglycemia during acute illness in a pediatric emergency
      department.
AB  - OBJECTIVES: Although mild stress hyperglycemia in pediatric illness is common,
      severe hyperglycemic responses (>=300 mg/dL [16.7 mmol/L]) to stress are unusual.
      We sought to determine the incidence and course of extreme stress hyperglycemia
      (ESH) in acute pediatric illness, including whether it is a marker of increased
      mortality or associated with subsequent development of diabetes mellitus (DM).
      METHODS: We retrospectively reviewed a cohort of 55,120 consecutive visits over 6
      years to a pediatric emergency department at which blood glucose concentrations
      were measured and report on visits with laboratory glucose 300 mg/dL (16.7
      mmol/L) or greater without DM. RESULTS: There were 72 cases of ESH (incidence of
      0.13%). Median age was 8.8 years; 63% were male. The most common diagnoses were
      respiratory illness (49%), trauma (15%), and seizure (8%), and 65% of patients
      had received glucose-influencing interventions before evaluation. Eighty-five
      percent were ill appearing, 60% were admitted to the intensive care unit, and
      half had acidemic pH values. The overall mortality rate was 22%. Despite
      treatment of hyperglycemia in only 8 patients, glucose concentrations decreased
      to 150 mg/dL (8.3 mmol/L) or less within 48 hours in 67% and before discharge or
      death in 85% of patients. Preceding symptoms and concurrent laboratory results
      were helpful to exclude diabetes, and none of the surviving patients with follow
      up available went on to develop type 1 or 2 DM. CONCLUSIONS: Although rare, ESH
      (>=300 mg/dL [16.7 mmol/L]) does occur in acute pediatric illness, in most cases
      is at least partially iatrogenic, and is a marker of severe illness and high
      mortality. Normoglycemia is typically restored quickly with treatment of the
      primary illness. No association was found with a subsequent diagnosis of DM.

PMID- 20805782
TI  - Residents' mental model of bag-mask ventilation.
AB  - OBJECTIVES: Our objectives were to characterize resident knowledge of bag-mask
      ventilation (BMV) and to identify predictors of a well-developed mental model of
      BMV. METHODS: A pilot survey of airway experts identified 6 steps considered
      essential in situations of difficult BMV. Subsequently, residents from pediatric,
      emergency medicine, and medicine-pediatric programs at a tertiary care hospital
      completed the same pediatric scenario-based item given to airway experts.
      RESULTS: Of all surveys, 75% (n = 103) were completed. No resident identified all
      6 maneuvers for difficult BMV. With decreasing frequency, the items identified
      were as follows: reposition patient/airway (82%), oral airway (61%), nasal airway
      (39%), jaw thrust (37%), 2-person technique (7%), and call for help (4%).
      Emergency medicine residents had a higher mean (SD) score than the medicine
      pediatric and pediatric residents of a possible 6 (2.71 (1.26) vs 2.01 (1.07), P
      = 0.004) and were significantly more likely to identify certain maneuvers: oral
      airway (81% vs 52%, P = 0.006), nasal airway (57% vs 29%, P = 0.006), and 2
      person technique (14% vs 3%, P = 0.042). Only 15% of all residents were able to
      identify 4 or more essential maneuvers. Higher level of training was associated
      with identifying the 2-person technique. In addition, residents who completed 1
      month of pediatric or adult anesthesia were more likely to identify use of nasal
      airway, oral airway and 2-person technique, and to identify 4 or more maneuvers.
      CONCLUSIONS: Emergency medicine residents identified more steps to optimize
      difficult BMV, although most residents exhibited a poorly developed mental model
      for difficult BMV compared with the consistent mental model of airway experts.
      Future research should investigate strategies for improving residents' mental
      model of BMV and its impact on patient care.

PMID- 20805783
TI  - Validation of a clinical score to predict skull fracture in head-injured infants.
AB  - OBJECTIVES: To validate a previously derived clinical score that uses clinical
      signs to determine which head-injured infants are at risk of skull fracture. The
      clinical score is calculated on the basis of the patient's age, the scalp
      hematoma size, and the location of the hematoma, with a total value between 0 and
      8. METHODS: We performed a prospective observational study of children younger
      than 2 years with blunt head trauma presenting to an urban pediatric emergency
      department. Among subjects who had head imaging performed (validation set), we
      assessed the utility of our clinical score to detect skull fracture and
      intracranial injury. RESULTS: In the 203 patients with imaging, 51 (25%) were
      diagnosed with skull fracture and 29 (14%) with intracranial injury. A clinical
      score of 4 or greater identified 90% (46/51) of patients with skull fracture with
      a sensitivity of 0.90 (95% confidence interval [CI], 0.78-0.96) and a specificity
      of 0.78 (95% CI, 0.70-0.84). A clinical score of 3 or greater identified 93%
      (27/29) of those with an intracranial injury with a sensitivity of 0.93 (95% CI,
      0.76-0.99) and a specificity of 0.42 (95% CI, 0.35-0.50). A score of 3 or greater
      identified 100% of intracranial injury among asymptomatic patients. CONCLUSIONS:
      We have validated our clinical scoring system as an accurate way of determining
      an infant's risk of skull fracture. Whereas a clinical score of 4 or greater
      maximizes the trade-off between sensitivity and specificity for identifying skull
      fracture, a clinical score of 3 or greater may be preferable for detecting
      intracranial injury.

PMID- 20805784
TI  - Delayed repeat enema in the management of intussusception.
AB  - OBJECTIVE: To describe the demographic and clinical characteristics of children
      with intussusception and failed initial air enema reduction who were managed by
      delayed repeat enema attempts and identify predictors associated with successful
      reduction. METHODS: This is a retrospective cross-sectional study of children
      diagnosed with intussusception who received care at an urban 110-bed children's
      hospital. Patients who had failed initial enema reduction attempts under
      fluoroscopic guidance and had subsequent delayed (>=2 hours from the initial
      attempt) repeat enemas made up the study population. The primary outcome variable
      was success of delayed repeat enema reduction. Predictor variables included
      duration of presenting symptoms (<=1 day vs >=2 days), gross bloody stools,
      dehydration, altered mental status, ileus per radiograph, time from initial to
      delayed repeat enema, and lack of partial reduction to the ileocecal valve with
      the first attempt. RESULTS: During a 74-month period, 20 patients with 21
      intussusception events managed by delayed repeat air enemas were identified. Of
      the 20 patients, there were 12 boys (60%). Distribution of race was as follows: 9
      white (45%), 7 African Americans (35%), and 4 Hispanics (20%). Of the 21 events,
      the mean (SD) age at the time of intussusception was 14.4 (12.8) months, with a
      median of 8 months and ranging from 2.5 to 43 months. Of the first 21 attempted
      delayed repeat enemas, 9 (43%) were successful. Of the 12 unsuccessful attempts,
      4 had a second delayed repeat enema attempt and 3 were successful. Overall
      delayed repeat enemas were successful in 12 patient events (57%). For the total
      25 delayed repeat enemas, 12 (48%) were successful.Surgical reduction was
      performed in 9 patient events (43%). Of these, manual reduction was performed in
      7 and surgical incision was performed in 2, with resection of a portion of the
      distal ileum. There were 19 ileocolic (90%) and 2 ileoileocolic (10%)
      intussusceptions. There were no pathologic lead points and no patient deaths.In
      comparing the successful from the failed delayed repeat enema reduction groups,
      there was no significant difference in demographic characteristics, clinical
      characteristics, or time from initial enema to first repeat enema. However, there
      was a trend toward a significant difference regarding the failed group having a
      greater rate of bloody stools, dehydration, or altered mental status. There was a
      significant difference for the degree of partial reduction achieved on the
      initial enema. For the successful delayed repeat enema reduction group, the
      location of the lead point of the intussusceptum after the initial enema was at
      the ileocecal valve for 9 patients (90%) versus 3 patients (33%) in the failed
      group. Although not significantly different, the successful versus failed delayed
      repeat enema reduction group trended toward significance regarding more patients
      with clinical improvement after initial enema (82% vs 43%). CONCLUSIONS: With the
      coordinated care of emergency medicine, surgery, and radiology services, delayed
      repeat enema seems to be an option to consider in the management of clinically
      stable children who, on initial air enema, have partial reduction. Our study
      showed that the success rate of delayed repeat enemas was greatest when the
      intussusceptum was initially reduced to the ileocecal valve.

PMID- 20805785
TI  - Clinical Implication of the C Allele of the ITPKC Gene SNP rs28493229 in Kawasaki
      Disease: Association With Disease Susceptibility and BCG Scar Reactivation.
AB  - BACKGROUND: a functional single nucleotide polymorphism (SNP) (rs28493229) in the
      inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) gene has been linked to the
      susceptibility to Kawasaki disease (KD). The implication remains unclear.
      SUBJECTS AND METHODS: genotyping for the ITPKC polymorphism was conducted on 280
      unrelated Taiwanese children with KD and 492 healthy ethnically and gender
      matched controls. The clinical manifestations and laboratory data were
      systemically collected. RESULTS: the GC and CC genotypes of ITPKC gene SNP
      rs28493229 were overrepresented in KD patients (GG:GC:CC was 236:43:1, C allele
      frequency: 8.04%) than those in the controls (GG:GC:CC was 454:37:1, C allele
      frequency: 3.96%; OR: 2.23, P = 0.001). In KD patients, those with GC or CC
      genotypes of SNP rs28493229 (19/44) were more likely to have reactivation at the
      Bacille Calmette-Guerin (BCG) inoculation site than those with GG genotypes
      (66/236; OR: 1.96, P = 0.044). Such association was particularly strong in
      patients aged <20 months (OR: 3.26, P = 0.017). The other clinical manifestations
      were not related to this SNP. There were 160 (57.1%) patients with coronary
      arterial lesions. The development and the severity of coronary arterial lesion
      were also not associated with this SNP. Comparison between patients with and
      without BCG reactivation revealed only one difference: patients with reactivation
      were younger. CONCLUSION: in a cohort from a population with the world's third
      highest incidence of KD, we demonstrated that the C-allele of ITPKC SNP
      rs28493229 is associated with KD susceptibility and BCG scar reactivation during
      the acute phase, although its frequency is lower than that in the Japanese cohort
      (22.6%), suggesting this SNP contributes to KD susceptibility through induced
      hyperimmune function reflected in the BCG reactivation.

PMID- 20805786
TI  - Etiology and epidemiology of viral pneumonia among hospitalized children in rural
      Mozambique: a malaria endemic area with high prevalence of human immunodeficiency
      virus.
AB  - BACKGROUND: The role of viruses in pediatric pneumonia remains poorly studied in
      sub-Saharan Africa, where pneumonia-associated mortality is high. METHODS: During
      a 1-year hospital-based surveillance, a nasopharyngeal aspirate (NPA) was
      collected from children aged <5 years admitted to hospital in rural Mozambique
      with clinically severe pneumonia. Identification of 12 respiratory viruses was
      performed by polymerase chain reactions (PCR). Study children were also tested
      for invasive bacterial infection (IBI), Plasmodium falciparum parasitemia, and
      HIV. RESULTS: Almost half (394/807) of the children hospitalized with clinically
      severe pneumonia had at least one respiratory virus detected. A total of 475
      viruses were detected among these 394 children, the most prevalent ones were
      rhinovirus (41%), adenovirus (21%), and respiratory syncytial virus (11%). Eleven
      percent of viral infected children had concomitant IBI, 15% had malaria
      parasites, and 25% had HIV coinfection. Viral infection was 5.5 to 16 times more
      prevalent among HIV-infected children and incidence rate ratios varied according
      to virus. Inhospital mortality of viral cases was 9%, being highest among cases
      with IBI coinfection (odds ratio = 7) or HIV infection (odds ratio = 7).
      CONCLUSIONS: Study results highlight the high prevalence of respiratory viruses
      among hospitalized pneumonia cases in Mozambique. HIV infection is an important
      contributor to the high burden of disease and associated mortality of viral
      pneumonia. IBI also contributes to a worse prognosis of viral cases. Strategies
      to prevent mother-to-child transmission of HIV as well as introduction of Hib and
      pneumococcal vaccines could have a substantial impact on reduction of viral
      pneumonia and associated mortality among children in rural Africa.

PMID- 20805787
TI  - NO inhibits hyperoxia-induced NF-kappaB activation in neonatal pulmonary
      microvascular endothelial cells.
AB  - Inhaled NO (iNO) may be protective against hyperoxic injury in the premature
      lung, but the mechanism is unknown. We hypothesized that NO would prevent
      hyperoxia-induced nuclear factor kappa B (NF-kappaB) activation in neonatal
      pulmonary microvascular endothelial cells [human pulmonary microvascular
      endothelial cell (HPMEC)] and prevent the up-regulation of target genes. After
      hyperoxic exposure (O2 >95%), nuclear NF-kappaB consensus sequence binding
      increased and was associated with IkappaBalpha degradation. Both of these
      findings were prevented by exposure to NO. Furthermore, intracellular adhesion
      molecule (ICAM)-1 mRNA and protein levels increased in cells exposed to
      hyperoxia, an effect abrogated by NO. To evaluate the potentially toxic effect of
      NO plus hyperoxia, cell viability and proliferation were assessed. Cells exposed
      to NO plus hyperoxia demonstrated improved survival as measured by trypan blue
      exclusion when compared with cells exposed to hyperoxia alone. These differences
      in cell death could not be attributed to apoptosis measured by caspase-3
      activity. Finally, cellular proliferation inhibited by hyperoxia was rescued by
      concurrent exposure to NO. These data demonstrate that NO prevents hyperoxia
      induced NF-kappaB activation in HPMEC and results in decreased expression of
      adhesion molecules and decreased cellular toxicity. This may help to explain the
      protective effects of NO on hyperoxic injury in the developing lung vasculature.

PMID- 20805788
TI  - Human neonatal peripheral blood leukocytes demonstrate pathogen-specific
      coordinate expression of TLR2, TLR4/MD2, and MyD88 during bacterial infection in
      vivo.
AB  - Toll-like receptors (TLRs) play important roles in infection. We have previously
      reported TLR2 is up-regulated in neonatal Gram-positive (G+) bacteremia, whereas
      TLR4 is up-regulated in neonatal Gram-negative (G-) bacteremia. For functional
      signaling, TLR4 requires myeloid differentiation (MD)-2, and both TLR2 and TLR4
      signal need myeloid differentiation factor (MyD88). However, it is unknown
      whether newborns can enhance expression of MD-2 and MyD88 with bacterial
      infection in coordination with TLR expression. We characterized neonatal
      peripheral blood leukocyte expression of MD-2 and MyD88 in relation to TLR2/4 in
      newborns. TLR2 mRNA expression by PBMCs and TLR2 protein expression by monocytes
      and granulocytes were significantly increased in the G+ bacteremia group. TLR4
      mRNA on PMBCs and protein expression on monocytes and granulocytes were
      significantly increased in the G- bacterial group. Remarkably, although, MyD88
      mRNA was increased in all patients with documented bacterial infection and
      correlated with both TLR2 and TLR4, MD-2 mRNA was selectively increased in G-
      bacterial group, wherein it correlated with TLR4 but not with TLR2 mRNA. Our
      findings demonstrate that during bacterial infection in vivo, newborns
      selectively and coordinately amplify the TLR2-MyD88 pathway in G+ bacterial
      infection and the TLR4/MD2/MyD88 pathway in G- bacterial infection, suggesting
      key roles for innate immune pathway in neonatal responses to bacterial infection.

PMID- 20805789
TI  - L-citrulline attenuates arrested alveolar growth and pulmonary hypertension in
      oxygen-induced lung injury in newborn rats.
AB  - Bronchopulmonary dysplasia (BPD) is characterized by arrested alveolar
      development and complicated by pulmonary hypertension (PH). NO promotes alveolar
      growth. Inhaled NO (iNO) ameliorates the BPD phenotype in experimental models and
      in some premature infants. Arginosuccinate synthetase (ASS) and arginosuccinate
      lyase (ASL) convert L-citrulline to L-arginine; L-citrulline is regenerated
      during NO synthesis from L-arginine. Plasma levels of these NO precursors are low
      in PH. We hypothesized that L-citrulline prevents experimental O2-induced BPD in
      newborn rats. Rat pups were assigned from birth through postnatal day (P) 14 to
      room air (RA), RA + L-citrulline, 95% hyperoxia (BPD model), and 95%O2 + L
      citrulline. Rat pups exposed to hyperoxia had fewer and enlarged air spaces and
      decreased capillary density, mimicking human BPD. This was associated with
      decreased plasma L-arginine and L-citrulline concentrations on P7. L-citrulline
      treatment significantly increased plasma L-arginine and L-citrulline
      concentrations and increased ASL protein expression in hyperoxia. L-citrulline
      preserved alveolar and vascular growth in O2-exposed pups and decreased pulmonary
      arterial medial wall thickness (MWT) and right ventricular hypertrophy (RVH).
      Increased lung arginase (ARG) activity in O2-exposed pups was reversed by L
      citrulline treatment. L-citrulline supplementation prevents hyperoxia-induced
      lung injury and PH in newborn rats. L-citrulline may represent a novel
      therapeutic alternative to iNO for prevention of BPD.

PMID- 20805790
TI  - Inhibition of fatty acid synthase in melanoma cells activates the intrinsic
      pathway of apoptosis.
AB  - Fatty acid synthase (FASN) is the metabolic enzyme responsible for the endogenous
      synthesis of the saturated long-chain fatty acid, palmitate. In contrast to most
      normal cells, FASN is overexpressed in a variety of human cancers, including
      cutaneous melanoma, in which its levels of expression are associated with tumor
      invasion and poor prognosis. We have previously shown that FASN inhibition with
      orlistat significantly reduces the number of spontaneous mediastinal lymph node
      metastases following the implantation of B16-F10 mouse melanoma cells in the
      peritoneal cavity of C57BL/6 mice. In this study, we investigate the biological
      mechanisms responsible for the FASN inhibition-induced apoptosis in B16-F10
      cells. Both FASN inhibitors, cerulenin and orlistat, significantly reduced
      melanoma cell proliferation and activated the intrinsic pathway of apoptosis, as
      demonstrated by the cytochrome c release and caspase-9 and -3 activation.
      Further, apoptosis was preceded by an increase in both reactive oxygen species
      production and cytosolic calcium concentrations and independent of p53 activation
      and mitochondrial permeability transition. Taken together, these findings
      demonstrate the mitochondrial involvement in FASN inhibition-induced apoptosis in
      melanoma cells.

PMID- 20805791
TI  - Role of extracellular membrane vesicles in the pathogenesis of various diseases,
      including cancer, renal diseases, atherosclerosis, and arthritis.
AB  - Extracellular membrane vesicles (MVs) 30-1000 nm in diameter and of varying
      cellular origins are increasingly recognized for their participation in a range
      of processes, including the pathogenesis of various diseases, such as: (1)
      atherosclerosis, (2) thromboembolism, (3) osteoarthritis (OA), (4) chronic renal
      disease and pulmonary hypertension, (5) tissue invasion and metastasis by cancer
      cells, (6) gastric ulcers and bacterial infections, and (7) periodontitis. MVs
      are derived from many different cell types and intracellular mechanisms, and
      perform different metabolic functions or roles, depending on the cell of
      origin.The presence of a metabolically active, outer membrane is a distinguishing
      feature of all MVs, regardless of their cell type of origin and irrespective of
      terminologies applied to them such as exosomes, microparticles, or matrix
      vesicles. The MV membrane provides one of the few protected and controlled
      internal microenvironments outside cells in which specific metabolic objectives
      of the host cell may be pursued vigorously at a distance from the host cell. MVs
      are also involved in various forms of normal and abnormal intercellular
      communication. Evidence is emerging that circulating MVs are good predictors of
      the severity of several diseases. In addition, recently, the role of MVs in
      inducing immunity against cancer cells and bacterial infections has become a
      topic of interest to researchers in the area of therapeutics. The main objective
      of this review is to list and briefly describe the increasingly well-defined
      roles of MVs in selected diseases in which they seem to have a significant role
      in pathogenesis.

PMID- 20805792
TI  - Exhaustive benchmarking of the yeast two-hybrid system.

PMID- 20805793
TI  - Rapidly denoising pyrosequencing amplicon reads by exploiting rank-abundance
      distributions.

PMID- 20805795
TI  - Mass spectrometry in high-throughput proteomics: ready for the big time.
AB  - Mass spectrometry has evolved and matured to a level where it is able to assess
      the complexity of the human proteome. We discuss some of the expected challenges
      ahead and promising strategies for success.

PMID- 20805796
TI  - MicroRNA profiling: separating signal from noise.
AB  - Various platforms for measuring microRNAs can provide different answers.

PMID- 20805797
TI  - C. elegans select.
AB  - The technical toolkit for Caenorhabditis elegans expands to include experimental
      selection using antibiotic resistance genes.

PMID- 20805798
TI  - Stem cells feel the difference.
AB  - Arrays of microposts of different heights generate substrates with different
      flexibility, on which cells can be grown.

PMID- 20805799
TI  - Oxygen maps in the brain.
AB  - Oxygen concentrations in the rodent brain are revealed at a microscopic scale by
      measuring the lifetime of two photon-excited phosphorescence.

PMID- 20805800
TI  - The knowledge of emergency contraception and dispensing practices of Patent
      Medicine Vendors in South West Nigeria.
AB  - Patent Medicine Vendors (PMVs) can play a critical role in increasing access to
      emergency contraceptive pills (ECPs) in developing countries, but few studies
      have examined their knowledge and dispensing practices. Using cluster sampling,
      the authors selected and interviewed 97 PMVs (60.8 per cent female) in Oyo and
      Ogun States of Nigeria to assess their knowledge, dispensing practices, and
      referral for ECPs. About one-third (27.8 per cent) of respondents were not aware
      of ECPs, and only half knew that ECPs could prevent pregnancy. Forty per cent had
      ever dispensed ECPs. Reasons proffered by those who do not dispense ECPs included
      barriers from the State Ministry of Health, police, other regulatory agencies,
      and religious beliefs. Only 50.5 per cent have referral arrangements for clients.
      Strategies to increase access to ECPs through PMVs include training on counseling
      techniques and referral, effective government regulation, and community
      involvement. Where unsafe abortion is a major cause of maternal mortality, these
      strategies offer protection for many women in the future.

PMID- 20805801
TI  - Commentary: Preventing pregnancy after unprotected sex: What options for Nigerian
      women?

PMID- 20805802
TI  - Working poor in Germany: Dimensions of the problem and repercussions for the
      health-care system.
AB  - The 'working poor' may not exceed the poverty threshold despite full-time (or
      even double) employment. The general relationship between poverty and illness is
      understood, but little is known about specific health implications of the
      'working poor' status. The proportion of 'working poor' is increasing in Germany.
      Poverty-related health problems occur because of a lower standard of nutrition
      and housing, financial restraints, bad labour conditions, high-risk behaviours,
      and lack of access to health services. Impaired health status, in turn, adversely
      affects incomes and wages, raising concern about a vicious circle. Limited health
      care resources demand preventive policies to improve employment status and
      income. Health and economic policy demand specific research on the health
      implications of precarious employment. In some areas, swift action is required.

PMID- 20805803
TI  - Commentary: Precarious employment: Adding a health inequalities perspective.

PMID- 20805804
TI  - A cluster of deaths following influenza vaccination, Israel, 2006.
AB  - When four deaths occurred in one week among influenza vaccine recipients, the
      Israeli Health Ministry suspended its 2006 influenza vaccination campaign pending
      investigation of the causes of death. Medical histories of the deceased
      vaccinees, quality control reports, and laboratory test results were examined.
      Prior vaccine use that season and a risk assessment of the vaccinated population
      were also considered. All four decedents had been treated for cardiac and other
      chronic diseases, and none had experienced post-injection symptoms suggesting
      adverse reaction to influenza vaccine. Quality control and laboratory reports
      confirmed vaccine batch safety, and no adverse effects had been reported among
      any other vaccine recipients. Investigators found no causal connection between
      the deaths and the vaccine, and the Health Ministry resumed the campaign. Israeli
      public health officials viewed the investigation as vital to maintaining broad
      confidence in the public health system, and in future vaccination campaigns.

PMID- 20805805
TI  - Who takes paternity leave? A cohort study on prior social and health
      characteristics among fathers in Stockholm.
AB  - Progress towards gender equality involves changes in the traditional parental
      division - female caring and male breadwinning. One aspect is increased parental
      leave for fathers, which may benefit the health of mothers, children, and fathers
      themselves. We examined how social and health characteristics (2002) were
      associated with paternity leave in excess of the 'father quota' of 60 days (2003
      2006) in the Stockholm Public Health Cohort. Generally, fathers with stable
      social position, fit lifestyles, and good health had increased chances of
      paternity leave uptake. Our findings may contribute to identifying target groups
      for parental leave strategies among fathers; they indicate also that research on
      gender equality and public health must carefully address the problems of
      confounding and health-related selection.

PMID- 20805806
TI  - Problems, policies and politics: A comparative case study of contraband tobacco
      from the 1990s to the present in the Canadian context.
AB  - Contraband tobacco has been and continues to be a global public health policy
      concern, with special manifestations in Canada. Over the past 20 years, in two
      noteworthy instances the Canadian government has battled contraband - in the
      early 1990s, and for much of the past decade. In the 1990s, when contraband
      cigarettes flooded the Canadian market, the government rapidly responded, using
      policy measures such as implementing a tobacco export tax and cutting domestic
      sales tax. Unfortunately, contraband made a strong comeback in recent years, but
      this time the government has hesitated to act, owing to a change in the source of
      the contraband. Using John Kingdon's streams theory to frame our arguments, we
      suggest that lack of congruence between different policy stakeholder groups'
      perceptions of the problem, policy solutions, and political feasibility has road
      blocked the implementation of anti-contraband policy in the 2000s.

PMID- 20805807
TI  - Barriers to tuberculosis control and prevention in undergraduates in Xi'an,
      China: A qualitative study.
AB  - To understand the barriers to tuberculosis (TB) control and prevention in
      undergraduate students and to propose the strategies to improve this work, we
      conducted in-depth interviews with three groups of individuals in infirmaries of
      universities and colleges, TB departments of district Centers for Disease Control
      and Prevention (CDCs), and undergraduates with TB. The study identified four
      major themes: inadequate workforce and less than optimal functioning of
      infirmaries and district TB control agencies; poor cooperation in the process of
      discovery, treatment, and surveillance of undergraduates with TB; poor acceptance
      of the national TB policy; and inadequate attention to TB prevention. Failure to
      carry out the national TB policy was the major barrier to TB control and
      prevention in undergraduates. TB control agencies should strengthen the
      implementation of the national TB policy.

PMID- 20805808
TI  - Why the United States lags in auto safety and lessons it can import.
AB  - The United States has slipped in recent decades from its role of leadership in
      combating road crash injuries. The early promise of the country's approach to
      vehicle safety regulation, adopted by law in 1966, has suffered because of
      decades of regulatory inertia caused by antiregulatory government policies,
      industry obstructionism, and failure to set meaningful goals. Meanwhile, other
      industrial nations have vastly outpaced the United States in reducing crash
      deaths and injuries. The Obama administration is thus challenged to learn from
      other nations' successes while reestablishing the US presence as a vigorous
      proponent of effective crash injury reduction strategies. It can best accomplish
      this by crafting approaches and objectives that reduce motor vehicle use, reduce
      harmful disparities within the US vehicle population, and reduce motor vehicle
      travel speeds.

PMID- 20805810
TI  - Marriage of cousins: Congenital diseases and people's perceptions in Pakistan, a
      public health challenge.

PMID- 20805812
TI  - Dr. Saulo Klahr, 1935-2010.

PMID- 20805814
TI  - The rise and fall of horror autotoxicus and forbidden clones.
AB  - Cui and associates show that healthy individuals have natural autoantibodies
      (NAAs) specific for myeloperoxidase, proteinase 3, and glomerular basement
      membrane (GBM) with the same specificity as anti-neutrophil cytoplasmic
      antibodies and anti-GBM antibodies that are pathogenic. Although Ehrlich proposed
      horror autotoxicus and Burnet envisioned elimination of forbidden clones, NAAs
      are present in all healthy individuals and play beneficial homeostatic roles.
      Pathogenic autoimmunity is dysregulation of natural homeostatic autoimmunity
      rather than onset of a previously absent self-recognition.

PMID- 20805815
TI  - Lead-time bias in studies of cinacalcet prescriptions.
AB  - Observational studies have suggested a link between higher serum phosphate,
      calcium, parathyroid hormone levels, and cardiovascular mortality. The
      administration of cinacalcet has proven efficient in the treatment of secondary
      hyperparathyroidism among hemodialysis patients. In an observational study by
      Block et al., cinacalcet treatment is associated with a much improved all-cause
      and cardiovascular mortality. However, the results should be interpreted
      cautiously, as observational studies may be influenced by bias. This Commentary
      discusses the role of some common potential biases.

PMID- 20805816
TI  - CD14 : a candidate biomarker for the prognosis of polycystic kidney disease.
AB  - Zhou et al. validate the expression of markers of the innate immune system in the
      cpk mouse model of polycystic kidney disease (PKD), in human recessive PKD, and
      in human autosomal dominant PKD and show that CD14 expression correlates with PKD
      progression, even from very early stages of disease. Moreover, they show that
      CD14 is expressed from the renal tubule epithelial cells, suggesting a mechanism
      of Toll-like receptor-4 activation in PKD prior to the infiltration of
      inflammatory cells.

PMID- 20805818
TI  - Primary systemic arterial vasodilation in cirrhotic patients.

PMID- 20805819
TI  - Only anti-CD133 antibodies recognizing the CD133/1 or the CD133/2 epitopes can
      identify human renal progenitors.

PMID- 20805820
TI  - Paraproteinemia-associated pseudohypercreatininemia across different analytical
      methodologies.

PMID- 20805823
TI  - Expression and localization of the ciliary disease protein retinitis pigmentosa
      GTPase regulator in mammalian kidney.

PMID- 20805824
TI  - A dialysis patient with a nodular tongue.

PMID- 20805825
TI  - The case | a blistering complication of peritoneal dialysis.

PMID- 20805826
TI  - Roux-en-Y gastric bypass surgery changes food reward in rats.
AB  - CONTEXT: Roux-en-Y gastric bypass surgery (RYGB) is currently the most effective
      treatment for morbid obesity, and clinical studies suggest that RYGB patients
      change food preferences and the desire to eat. OBJECTIVE: To examine hedonic
      reactions to palatable foods and food choice behavior in an established rat model
      of RYGB. METHODS AND DESIGN: Male Sprague-Dawley (SD) rats and selected line
      obesity-prone rats that were rendered obese on a high-fat diet underwent RYGB or
      sham surgery and were tested for 'liking' and 'wanting' of palatable foods at
      different caloric densities 4-6 months after surgery. RESULTS: Compared with sham
      operated (obese) and age-matched lean control rats, RYGB rats of both models
      exhibited more positive orofacial responses to low concentrations of sucrose but
      fewer to high concentrations. These changes in 'liking' by RYGB rats were
      translated into a shift of the concentration-response curve in the brief access
      test, with more vigorous licking of low concentrations of sucrose and corn oil,
      but less licking of the highest concentrations. The changes in hedonic evaluation
      also resulted in lower long-term preference/acceptance of high-fat diets compared
      with sham-operated (obese) rats. Furthermore, the reduced 'wanting' of a
      palatable reward in the incentive runway seen in sham-operated obese SD rats was
      fully restored after RYGB to the level found in lean control rats. CONCLUSIONS:
      The results suggest that RYGB leads to a shift in hedonic evaluation, favoring
      low over high calorie foods and restores obesity-induced alterations in 'liking'
      and 'wanting'. It remains to be determined whether these effects are simply due
      to weight loss or specific changes in gut-brain communication. Given the emerging
      evidence for modulation of cortico-limbic brain structures involved in reward
      mechanisms by gut hormones, RYGB-induced changes in the secretion of these
      hormones could potentially be mediating these effects.

PMID- 20805828
TI  - Fructose as cause of metabolic syndrome is poorly supported.

PMID- 20805827
TI  - Infant temperament and eating style predict change in standardized weight status
      and obesity risk at 6 years of age.
AB  - OBJECTIVE: Little research has addressed the relationships among infant
      temperament, eating styles and obesity risk. To address this gap, we tested
      whether infant temperament and eating patterns at the age of 1 year are
      associated with a greater increase in standardized weight status, and greater
      obesity risk at 6 years of age. DESIGN: A secondary, prospective analysis of the
      Colorado Adoption Study was conducted. The main predictor variables were infant
      temperament (that is, emotionality, activity, attention span-persistence,
      reaction to food and soothability) and eating domains (that is, reactivity to
      food, predictable appetite and distractability at mealtime) at the age of 1 year,
      along with the body mass index (BMI) of biological mothers. The outcome measures
      were child weight and height (length) assessed at ages 1 through 6 years, from
      which weight-for-length and BMI were computed along with the standardized indexes
      (z-scores) and percentiles. Overweight/obesity status was computed at each year
      as well. PARTICIPANTS: A primarily White sample of 262 boys and 225 girls,
      assessed at ages 1 through 6 years, along with their mothers. RESULTS: Among
      boys, greater attention span-persistence was associated with reduced standardized
      weight status gain (beta=-0.15, P<0.05) and reduced obesity risk (odds ratio
      (OR)=0.46, P=0.06). Among girls, greater soothability and negative reaction to
      food were associated with greater standardized weight status gain (beta=0.19,
      P<0.01; and beta=0.16, P<0.05, respectively) and increased obesity risk (OR=3.72,
      P=0.03; and OR=2.81, P=0.08, respectively). Biological mothers' obesity status
      predicted obesity risk in boys (OR=3.07, P=0.01) and girls (OR=5.94, P=0.03).
      CONCLUSIONS: Male infants with less attention span, and female infants with
      greater soothability or a more negative food reaction, showed greater increases
      in standardized weight and were more likely to be overweight/obese at the age of
      6 years. The role of infant temperament in pediatric obesity onset warrants
      greater research.

PMID- 20805829
TI  - Relationships between pregnancy outcomes, biochemical markers and pre-pregnancy
      body mass index.
AB  - OBJECTIVE: We examined the relationships between pre-pregnancy maternal body mass
      index (BMI), pregnancy outcomes and biochemical markers. DESIGN: This study was
      conducted as a cross-sectional analysis. SUBJECTS: Korean women in their second
      and third trimesters of pregnancy were recruited at two hospitals in the
      metropolitan Seoul area. Pre-pregnancy BMI was categorized in four groups
      according to the Asia-Pacific standard. MEASUREMENTS: Fasting blood samples were
      obtained and analyzed for serum levels of homocysteine, folate and high
      sensitivity C-reactive protein (hs-CRP). Concentrations of fetal fibronectin were
      assessed in the cervix and vagina, and cervical length was measured. RESULTS:
      Obese subjects had a lower education level and a lower income level than subjects
      of normal weight. The level of maternal stress was positively associated with pre
      pregnancy BMI. Normal weight subjects were more likely to eat breakfast and
      consume meals of appropriate size than the rest of our sample. In overweight and
      obese subjects, weight gain during pregnancy was significantly lower than in the
      underweight and normal subjects. High pre-pregnancy maternal BMI increased the
      risks of preterm delivery (odds ratio (OR)=2.85, confidence interval (CI)=1.20
      6.74), low-birth-weight (LBW) infants (overweight subjects: OR=5.07, CI=1.76
      14.63; obese subjects: OR=4.49, CI=1.54-13.13) and macrosomia. In obese subjects,
      the average serum folate level was significantly lower than in the underweight
      subjects. In obese subjects, the average serum hs-CRP level was significantly
      higher than in the rest of our sample. CONCLUSION: Pregnancy outcomes are
      influenced by pre-pregnancy BMI. These findings suggest that women can minimize
      their risks of preterm delivery, LBW and macrosomia by maintaining normal pre
      pregnancy BMI.

PMID- 20805830
TI  - Respiratory muscle endurance training in obese patients.
AB  - OBJECTIVE: Increased respiratory muscle work is associated with dyspnea and poor
      exercise tolerance in obese patients. We evaluated the effect of respiratory
      muscle endurance training (RMET) on respiratory muscle capacities, symptoms and
      exercise capacity in obese patients. DESIGN: A total of 20 obese patients
      hospitalized for 26 +/- 6 days to follow a low-calorie diet and a physical
      activity program were included in this case-control study. Of them, 10 patients
      performed RMET (30-min isocapnic hyperpnea at 60-80% maximum voluntary
      ventilation, 3-4 times per week during the whole hospitalization period: RMET
      group), while the other 10 patients performed no respiratory training (control
      (CON) group). RMET and CON groups were matched for body mass index (BMI) (45 +/-
      7 kg m(-2)) and age (42 +/- 12 years). Lung function, respiratory muscle strength
      and endurance, 6-min walking distance, dyspnea (Medical Research Council scale)
      and quality of life (short-form health survey 36 questionnaire) were assessed
      before and after intervention. RESULTS: Similar BMI reduction was observed after
      hospitalization in the RMET and CON groups (-2 +/- 1 kg m(-2), P < 0.001). No
      significant change in lung function and respiratory muscle strength was observed
      except for vital capacity, which increased in the RMET group (+0.20 +/- 0.26 l, P
      = 0.039). Respiratory muscle endurance increased in the RMET group only (+52 +/-
      27%, P < 0.001). Compared with the CON group, the RMET group had greater
      improvement in 6MWT (+54 +/- 35 versus +1 +/- 7 m, P = 0.007), dyspnea score (-2
      +/- 1 versus -1 +/- 1 points, P = 0.047) and quality of life (total score: +251
      +/- 132 versus +84 +/- 152 points, P = 0.018) after hospitalization. A
      significant correlation between the increase in respiratory muscle endurance and
      improvement in 6MWT distance was observed (r (2) = 0.36, P = 0.005). CONCLUSIONS:
      The present study indicates that RMET is feasible in obese patients and can
      induce significant improvement in dyspnea and exercise capacity. RMET may be a
      promising tool to improve functional capacity and adherence to physical
      activities in this population, but further studies are needed to confirm these
      results.

PMID- 20805831
TI  - Hyperphosphorylated neurofilament NF-H as a biomarker of the efficacy of
      minocycline therapy for spinal cord injury.
AB  - STUDY DESIGN: An in vivo study in a rat model of acute spinal cord contusion.
      OBJECTIVES: To assess the efficacy of novel therapies for acute spinal cord
      injury (SCI), methods to evaluate accurately the effects of these therapies
      should be developed. Although neurological examination is commonly used for this
      purpose, unstable clinical conditions and the spontaneous recovery of
      neurological function in the acute and subacute phases after injury make this
      measurement unreliable. Recent studies have reported that the phosphorylated form
      of the high-molecular-weight neurofilament subunit NF-H (pNF-H), a new biomarker
      for axonal degeneration, can be measured in serum samples in experimental SCI
      animals. Therefore, we aimed to investigate the use of plasma pNF-H as an
      indicator of the efficacy of minocycline, a neuroprotective drug, for treating
      SCI. SETTING: This study was carried out at Saitama, Japan. METHODS: Spinal cord
      injured rats received either minocycline or saline intraperitoneally. The plasma
      pNF-H levels and functional hind limb score were determined after the injury.
      RESULTS: Minocycline treatment reduced plasma pNF-H levels at 3 and 4 days post
      injury (dpi). Rats with lower plasma pNF-H levels at 3 dpi had higher hind limb
      motor score at 28 dpi. CONCLUSIONS: pNF-H levels may serve as a biomarker for
      evaluating the efficacy of therapies for SCI.

PMID- 20805832
TI  - Reply to Katsumi et al.

PMID- 20805833
TI  - Barriers and facilitators to employment after spinal cord injury: underlying
      dimensions and their relationship to labor force participation.
AB  - STUDY DESIGN: Cross-sectional survey. OBJECTIVE: To identify barriers and
      facilitators to employment after spinal cord injury (SCI) and their relationship
      with labor force participation. METHODS: Participants were initially identified
      through specialty hospitals in the Midwest and Southeastern United States of
      America. 781 adults with traumatic SCI, at least 1 year post-injury, and between
      the ages of 18-64, participated. A 30-item instrument on barriers and
      facilitators to employment was administered. Analyses included exploratory factor
      analysis (EFA), confirmatory factor analysis (CFA) and comparisons of scores as a
      function of employment status. RESULTS: EFA indicated six primary themes (root
      mean square error of approximation (RMSEA)=0.040), including: (a) resources, (b)
      health status, (c) disability considerations, (d) lack of importance, (e)
      disincentives and (f) motivation. CFA indicated an acceptable fit (RMSEA=0.078).
      Univariate analyses indicated each item and factor was significantly different as
      a function of labor force participation. After controlling for biographical and
      injury factors, multinomial logistic regression indicated three factors
      significantly differentiated those never employed, those currently unemployed but
      had worked since injury and those currently employed. Those employed reported
      higher scores for resources and motivation and lower scores for lack of
      importance. CONCLUSIONS: Barriers and facilitators were consistently related to
      labor force participation, with facilitators more highly related to labor force
      participation than barriers. Although loss of financial and medical benefits
      (disincentives) as well as health status have been reported as barriers to
      employment, they were not as highly correlated with labor force participation as
      were other factors.

PMID- 20805834
TI  - Is the outcome in acute spinal cord ischaemia different from that in traumatic
      spinal cord injury? A cross-sectional analysis of the neurological and functional
      outcome in a cohort of 93 paraplegics.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To compare the neurological
      outcome between paraplegic patients with acute spinal cord ischaemia syndrome
      (ASCIS) or traumatic spinal cord injury (tSCI) and to investigate the influence
      of SCI aetiology on the total Spinal Cord Independence Measure (SCIM)-II score.
      SETTING: Level 1 trauma centre. METHODS: Initial (0-40 days) and chronic-phase (6
      12 months) American Spinal Injury Association (ASIA) sensory scores, lower
      extremity motor score (LEMS) and chronic-phase total SCIM-II scores were
      analysed. Differences between ASCIS and tSCI patients were calculated using
      Student's t-tests and Wilcoxon signed-rank tests. To assess which variables give
      rise to the prediction of total SCIM-II score, a multiple linear regression
      analysis was used. These predictor variables included complete (ASIA impairment
      scale A) or incomplete SCI (AIS B, C, and D), aetiology, age and gender. RESULTS:
      Out of 93 included patients, 20 ASCIS and 73 tSCI patients were identified. In
      the complete SCI group, the initial pinprick scores were higher (P<0.05) in ASCIS
      patients compared with tSCI patients, 37.9 (95% Confidence Interval (CI), 23.3
      52.5) and 27.3 (95% CI, 24.1-30.4), respectively. No other relevant differences
      in neurological outcome were identified between ASCIS and tSCI patients; however,
      the total SCIM-II scores were higher (P<0.05) in tSCI patients after 12 months.
      Using the linear regression analysis, we were able to predict 31.4% of the
      variability. The aetiology was not significant in this model. CONCLUSION: The
      neurological outcome was independent of the diagnosis ASCIS or tSCI. Furthermore,
      the diagnosis ASCIS or tSCI was not a significant predictor for total SCIM II
      scores after 12 months. SPONSORSHIP: This study was granted by the
      'Internationale Stiftung fur Forschung in Paraplegie' (IFP), Zurich, Switzerland.

PMID- 20805836
TI  - Anarchy for the EMBC.

PMID- 20805837
TI  - Managing academic research.

PMID- 20805835
TI  - Advantages and limitations of current network inference methods.
AB  - Network inference, which is the reconstruction of biological networks from high
      throughput data, can provide valuable information about the regulation of gene
      expression in cells. However, it is an underdetermined problem, as the number of
      interactions that can be inferred exceeds the number of independent measurements.
      Different state-of-the-art tools for network inference use specific assumptions
      and simplifications to deal with underdetermination, and these influence the
      inferences. The outcome of network inference therefore varies between tools and
      can be highly complementary. Here we categorize the available tools according to
      the strategies that they use to deal with the problem of underdetermination. Such
      categorization allows an insight into why a certain tool is more appropriate for
      the specific research question or data set at hand.

PMID- 20805838
TI  - Dynein at the nuclear envelope.

PMID- 20805839
TI  - B for bureaucracy.

PMID- 20805840
TI  - The psycho gene.

PMID- 20805841
TI  - Bystander inhibition of dendritic cell differentiation by Mycobacterium
      tuberculosis-induced IL-10.
AB  - Mycobacterium tuberculosis (Mtb) evades the immune response by impairing the
      functions of different antigen-presenting cells. We have recently shown that Mtb
      hijacks differentiation of monocytes into dendritic cells (DCs). To further
      characterize the mechanisms underlying this process, we investigated the
      consequences of inducing dendritic cell differentiation using interferon-alpha
      and granulocyte-macrophage colony-stimulating factor in the presence of
      supernatants (SNs) obtained from monocyte cultures treated with or without heat
      inactivated Mtb. Although the SNs from control cultures do not interfere with the
      generation of fully differentiated DCs, monocytes stimulated with SNs from Mtb
      stimulated cells (SN Mtb) remained CD14(+) and poorly differentiated into CD1a(+)
      cells. Among cytokines known to affect dendritic cell differentiation, we
      observed a robust production of interleukin-1beta, interleukin-6, interleukin-10
      and tumor necrosis factor-alpha upon Mtb stimulation. However, only interleukin
      10 neutralization through the addition of soluble interleukin-10 receptor
      reversed the inhibitory activity of SN Mtb. Accordingly, the addition of
      recombinant interleukin-10 was able to significantly reduce CD1a expression. The
      interaction of Mtb with differentiating monocytes rapidly activates p38 mitogen
      activated protein kinase, signal transducer and activator of transcription
      pathways, which are likely involved in interleukin-10 gene expression. Taken
      together, our results suggest that Mtb may inhibit the differentiation of
      bystander non-infected monocytes into DCs through the release of interleukin-10.
      These results shed light on new aspects of the host-pathogen interaction, which
      might help to identify innovative immunological strategies to limit Mtb
      virulence.

PMID- 20805842
TI  - The lymphoid chemokine CCL21 triggers LFA-1 adhesive properties on human
      dendritic cells.
AB  - Dendritic cells (DCs) are the most potent APCs, involved in the induction of
      immunity and tolerance. Recently we showed that during differentiation of human
      DCs from monocyte precursors, Lymphocyte function-associated antigen-1 (LFA-1)
      binding capacity is lost, although integrin expression levels were maintained
      constant, suggesting a different regulation mechanism of this integrin on
      different cell types. However, the exact role of LFA-1 in DC adhesion and
      migration remains obscure. Chemokines are potent regulators of integrin function,
      influencing migratory and adhesive properties of leukocytes. Here, we show that
      upon vaccination of cancer patients with human DCs, cells that have migrated in
      vivo into the lymph nodes upregulated the active form of LFA-1. We further show
      that exposure of human DCs to the lymphoid chemokine CCL21 specifically restores
      the high-affinity form of LFA-1 and induces binding to its ligand ICAM-1 under
      low shear stress. Our data indicate that on DCs LFA-1 may function as an
      inducible anchor during lymphatic transmigration or within the lymph nodes. A
      thorough understanding of the adhesive events during the DC life cycle will help
      to improve the outcome of DC-based antitumor clinical trials.

PMID- 20805843
TI  - New insight into cancer therapeutics: induction of differentiation by regulating
      the Musashi/Numb/Notch pathway.

PMID- 20805845
TI  - Lipid-laden dendritic cells fail to function.

PMID- 20805846
TI  - [The dangerous silence].

PMID- 20805844
TI  - Physiological levels of ATP negatively regulate proteasome function.
AB  - Intracellular protein degradation by the ubiquitin-proteasome system is ATP
      dependent, and the optimal ATP concentration to activate proteasome function in
      vitro is ~100 MUM. Intracellular ATP levels are generally in the low millimolar
      range, but ATP at a level within this range was shown to inhibit proteasome
      peptidase activities in vitro. Here, we report new evidence that supports a
      hypothesis that intracellular ATP at the physiological levels bidirectionally
      regulates 26S proteasome proteolytic function in the cell. First, we confirmed
      that ATP exerted bidirectional regulation on the 26S proteasome in vitro, with
      the optimal ATP concentration (between 50 and 100 MUM) stimulating proteasome
      chymotrypsin-like activities. Second, we found that manipulating intracellular
      ATP levels also led to bidirectional changes in the levels of proteasome-specific
      protein substrates in cultured cells. Finally, measures to increase intracellular
      ATP enhanced, while decreasing intracellular ATP attenuated the ability of
      proteasome inhibition to induce cell death. These data strongly suggest that
      endogenous ATP within the physiological concentration range can exert a negative
      impact on proteasome activities, allowing the cell to rapidly upregulate
      proteasome activity on ATP reduction under stress conditions.

PMID- 20805847
TI  - [Think of a number!].

PMID- 20805848
TI  - [Distorted picture of whiplash injury problems].

PMID- 20805849
TI  - [Health economics and anecdotal references].

PMID- 20805850
TI  - [The difficult neonatology].

PMID- 20805851
TI  - [Common misunderstandings about maternal mortality].

PMID- 20805854
TI  - [Colorectal cancer screening].

PMID- 20805855
TI  - [The battle against HIV can be won, but there is not enough money!].

PMID- 20805853
TI  - [Specialist education and the inadequate debate].

PMID- 20805856
TI  - [Coding practice in fatal poisonings].
AB  - BACKGROUND: Each year, nearly 100 deaths and more than 10,000 admissions to
      Norwegian hospitals can be attributed to acute poisoning from non-medical
      substances and drugs in supra-therapeutic doses. The aim of this study was to
      evaluate hospitals' routines for coding of acute poisoning deaths and to provide
      information on the toxic agents involved. MATERIAL AND METHODS: Medical records
      of deaths (at 6 Norwegian hospitals in the period 1.1.1999 -31.12.2005) due to
      acute poisoning were re-examined to assess accuracy of diagnosis codes. RESULTS:
      Acute poisoning was registered as the cause of 225 deaths in the study period.
      The re-evaluation concluded that 45 of these deaths had other causes. In 125 of
      the remaining 180 deaths, acute poisoning was only registered as a side
      diagnosis, although re-examination revealed it was the major contribution to
      death in 66 % (83 of 125) of cases. The hospitals had classified the drugs
      according to ATC codes in 16 % (28 of 180) of patients with acute poisoning.
      INTERPRETATION: The present Norwegian coding practice does not document acute
      poisoning deaths in hospital correctly, and registry studies based on diagnosis
      codes should be interpreted with care. Current registration of poisoning agents'
      ATC-codes is insufficient and the Norwegian version of ICD-10 alone is not
      suitable for classification of acute drug poisoning. Replacement of the Norwegian
      ICD-10 version by the original international version should be considered and/or
      the routines for registration of ATC-codes should be improved.

PMID- 20805857
TI  - [Clinical trials--viewpoints from participants].
AB  - BACKGROUND: In relation to the large number of clinical trials performed, little
      is written about how the study subjects have experienced their participation. The
      article presents the results from a questionnaire survey among participants in 18
      clinical trials undertaken at the Lipid Clinic, Rikshospitalet, Norway in 2005
      and 2006. MATERIAL AND METHODS: A study-specific questionnaire was developed and
      comprised 17 questions about study participation. Response was anonymous. Results
      are given as percentage distribution of answers. RESULTS: 56 % (287 persons)
      completed the questionnaire. Motivation for study participation was twofold, both
      personal health gains and the desire to contribute to research and development
      are important motives. 28 % [corrected] thought the new drug could be beneficial
      for them. Study participants responded the following: 90 % meant that the risk of
      adverse events and harmful effects of the study drug was small, 73 % that follow
      up was good, 85 % that they had received sufficient information about the study
      and 77 % that study participation had no disadvantages. 73 % thought it had a
      positive health impact for them to be involved in the study. INTERPRETATION:
      Participants in our clinical trials are concerned about their own health, but
      they also want to contribute to research for the well-being of others. Study
      participants seem to overestimate the health benefits associated with use of the
      study drug. Frequent medical follow-up and guidance in diet and lifestyle are
      benefits associated with participation in clinical studies, but the effects are
      difficult to measure.

PMID- 20805858
TI  - [Intensive care of patients with acute liver failure].
AB  - BACKGROUND: Acute liver failure and acute decompensated chronic liver failure are
      two diseases that demand extensive knowledge of etiology and triggering factors,
      pathophysiology, diagnosis, prognosis and recommended guidelines for treatment.
      The article defines the diseases, discusses etiological factors, treatment
      strategies, indications for referral to the transplantation unit at
      Rikshospitalet and prognostic factors of importance. MATERIAL AND METHODS: The
      basis for this article is literature identified through a non-systematic search
      in PubMed and the authors' clinical experience and experimental research within
      the field. RESULTS: In the Western world paracetamol poisoning and toxic
      reactions to other drugs are the most common triggering factors for acute liver
      poisoning in adults. Patients can quickly develop multi organ failure requiring
      advanced intensive care. The most common complications are hepatic
      encephalopathy, acute renal failure and coagulation disturbances. Acute
      decompensated chronic liver failure strikes patients with known liver disease and
      is most often triggered by inflammation, infection, gastrointestinal bleeding,
      drugs, traumas or disturbances in acid/base/electrolyte balance. Early diagnosing
      of triggering factors and intensive medical supportive treatment is especially
      important. Acute renal failure indicates a very bad prognosis. INTERPRETATION:
      Patients diagnosed with acute liver failure or acute decompensated chronic liver
      failure remain a clinical challenge. Optimal treatment requires extensive
      knowledge of pathophysiological mechanisms and treatment strategies.

PMID- 20805859
TI  - [The treatment of femoral neck fractures].
AB  - BACKGROUND: About 5000 people fracture their femoral neck every year in Norway.
      Mean age is about 83 years and about 3/4 are women. For more than 50 years the
      alternatives have been internal fixation or arthroplasty. In Norway, the
      tradition has been internal fixation. Recent studies, however, support the use of
      arthroplasty. The article provides a review on the treatment of femoral neck
      fractures. MATERIAL AND METHODS: The article is based on literature identified
      through a non-systematic search in Medline. RESULTS: Internal fixation has a
      higher risk of treatment failure (30 - 40 % in displaced fractures) than
      arthroplasty (less than 10 %). In elderly patients with displaced fractures,
      arthroplasty provides better hip function than internal fixation. Most patients
      should be treated with hemiarthroplasty, but total hip arthroplasty may give
      better function in the healthiest and fittest of the elderly patients. In
      patients younger than 60 - 65 years, internal fixation should be attempted, even
      though the failure rate is about 30 %. Undisplaced fractures should be treated
      with internal fixation, irrespective of age. The risk of treatment failure is
      about 10 %. INTERPRETATION: Elderly patients with displaced femoral neck
      fractures should be treated with arthroplasty, usually hemiarthroplasty.
      Osteosynthesis should normally be reserved for undisplaced fractures and
      fractures in young and otherwise healthy patients.

PMID- 20805860
TI  - [Malpositioning of umbilical vessel catheters].
AB  - BACKGROUND: Catheterization of umbilical veins and arteries is a common
      intervention in newborns. Malpositioning of catheters is associated with
      complications. The objective of this study was to evaluate catheter positions
      after insertion. MATERIAL AND METHODS: The study is based on retrospective
      evaluation of all relevant X-ray images of newborns admitted to the neonatal
      intensive care unit, Vestfold Hospital, Norway in the period 1.06.98 - 28.02.10.
      Accurate localization of the catheter tip was determined in all images. In term
      infants, acceptable positioning for venous catheters was defined as <or= 10 mm
      above or below the level of diaphragma and in preterm infants <or= 5 mm. For
      arterial catheters, acceptable positioning of the catheter tip (irrespective of
      gestational age) was at the level of the 6th to 9th thoracic vertebral body (high
      position, preferred) or at the 3rd to 4th lumbar vertebral body (low position).
      RESULTS: 278 umbilical vein and 99 umbilical artery catheters were inserted in
      298 patients. 45/99 (45 %) of the arterial catheters and 77/278 (28 %) of the
      venous catheters were correctly positioned from the start. Significantly more
      arterial catheters were positioned too low (44/99; 44 %) than too high (10/99; 10
      %) (p < 0.001). Correspondingly, more venous catheters were positioned too low
      (126/278; 45 %) than too high (75/278; 27 %) (p < 0.001). Coiling occurred in 14
      (5 %) venous catheters and in 6 (6 %) arterial catheters. INTERPRETATIONS:
      Umbilical vessel catheters are often malpositioned. This increases the risk of
      thromboses and circulation disturbances. X-ray images are important for
      evaluation and potential correction of the catheter position.

PMID- 20805861
TI  - [Tigecycline--a new antibiotic].
AB  - Tigecycline belongs to a new class of antimicrobial agents, the glycylcyclines,
      which are structurally derived from tetracyclines. It is effective against both
      gram positive and gram negative bacteria, aerobes and anaerobes and bacteria that
      have developed resistance against the classic tetracyclines. Although there is an
      increased risk for serious adverse events, tigecycline is important for treatment
      of patients with complicated infections of moderate severity where other
      antimicrobials cannot be used.

PMID- 20805862
TI  - [A young man with acute, generalised oedema].
AB  - BACKGROUND: Menetrier disease is an uncommon, idiopathic disease characterized by
      development of chronic protein loss from marked gastric foveolar hyperplasia. A
      literature search identified several reports of self-limiting, cytomegalovirus
      associated Menetrier disease in children. Some cases have also been reported in
      adults. CASE REPORT: A formerly healthy man was admitted to hospital with a serum
      albumin level of 11 g/l and generalised oedema. Transabdominal ultrasound and
      endoscopy revealed a folded thickening of the (abdominal) ventricular wall;
      indications of Menetrier disease. Histological examination of endoscopic biopsies
      showed moderate hyperplasia in foveolar epithelium, but also suggested an
      infectious cause. Intranucleal inclusion bodies, CMV-specific immunology, PCR and
      special stains all supported cytomegalovirus infection. The patient recovered
      quickly on antiviral treatment. CONCLUSION: Our case demonstrates that
      cytomegalovirus may cause severe, Menetrier-like gastritis with protein loss in
      non-immune-compromised adults.

PMID- 20805863
TI  - [An unusual gastrointestinal protein loss].

PMID- 20805864
TI  - [The comprehensive summary of doctoral dissertation--what should it contain?].

PMID- 20805866
TI  - [Emergency medicine education in USA].

PMID- 20805868
TI  - Serum dipeptidyl peptidase-4 activity in insulin resistant patients with non
      alcoholic fatty liver disease: a novel liver disease biomarker.
AB  - BACKGROUND: In a cross-sectional study we studied the fasting serum DPP-4
      enzymatic activity (sDPP-4) and the insulin resistance index (HOMA2-IR) in
      gliptin naive patients with type 2 diabetes and in non-alcoholic fatty liver
      disease (NAFLD) and in healthy controls (CNTRL). METHODS AND FINDINGS: sDPP-4 was
      measured by kinetic assay in 39 NAFLD (F/M:19/20, mean age: 47.42 yrs) and 82
      type 2 diabetes (F/M:48/34, 62.8 yrs) patients and 26 (F/M:14/12, 35.3 yrs)
      controls. Definition of T2D group as patients with type 2 diabetes but without
      clinically obvious liver disease created non-overlapping study groups. Diagnosis
      of NAFLD was based on ultrasonography and the exclusion of other etiololgy.
      Patients in T2D and NAFLD groups were similarly obese. 75 g CH OGTT in 39 NAFLD
      patients: 24-NGT, 4-IGT or IFG ("prediabetes"), 11-type 2 diabetes. HOMA2-IR:
      CNTRL: 1.44; T2D-group: 2.62 (p = 0.046 vs CNTRL, parametric tests);
      NAFLD(NGTonly): 3.23 (p = 0.0013 vs CNTRL); NAFLD(IFG/IGT/type 2 diabetes): 3.82
      (p<0.001 vs CNTRL, p = 0.049 vs 2TD group). sDPP-4 activity was higher in NAFLD
      both with NGT (mean:33.08U/L) and abnormal glucose metabolism (30.38U/L) than in
      CNTRL (25.89U/L, p<0.001 and p = 0.013) or in T2D groups (23.97U/L, p<0.001 and p
      = 0.004). Correlations in NAFLD among sDPP-4 and ALT: r = 0.4637,p = 0.0038 and
      gammaGT: r = 0.4991,p = 0.0017 and HOMA2-IR: r = 0.5295,p = 0.0026 and among
      HOMA2-IR and ALT: r = 0.4340,p = 0.0147 and gammaGT: r = 0.4128,p = 0.0210.
      CONCLUSIONS: The fasting serum DPP-4 activity was not increased in T2D provided
      that patients with liver disease were intentionally excluded. The high serum DPP
      4 activities in NAFLD were correlated with liver tests but not with the fasting
      plasma glucose or HbA1C supporting that the excess is of hepatic origin and it
      might contribute to the speedup of metabolic deterioration. The correlation among
      gammaGT, ALT and serum DPP-4 activity and also between serum DPP-4 activity and
      HOMA2-IR in NAFLD strongly suggests that serum DPP-4 activity should be
      considered as a novel liver disease biomarker.

PMID- 20805869
TI  - Emerging infectious disease leads to rapid population declines of common British
      birds.
AB  - Emerging infectious diseases are increasingly cited as threats to wildlife,
      livestock and humans alike. They can threaten geographically isolated or
      critically endangered wildlife populations; however, relatively few studies have
      clearly demonstrated the extent to which emerging diseases can impact populations
      of common wildlife species. Here, we report the impact of an emerging protozoal
      disease on British populations of greenfinch Carduelis chloris and chaffinch
      Fringilla coelebs, two of the most common birds in Britain. Morphological and
      molecular analyses showed this to be due to Trichomonas gallinae. Trichomonosis
      emerged as a novel fatal disease of finches in Britain in 2005 and rapidly became
      epidemic within greenfinch, and to a lesser extent chaffinch, populations in
      2006. By 2007, breeding populations of greenfinches and chaffinches in the
      geographic region of highest disease incidence had decreased by 35% and 21%
      respectively, representing mortality in excess of half a million birds. In
      contrast, declines were less pronounced or absent in these species in regions
      where the disease was found in intermediate or low incidence. Also, populations
      of dunnock Prunella modularis, which similarly feeds in gardens, but in which T.
      gallinae was rarely recorded, did not decline. This is the first trichomonosis
      epidemic reported in the scientific literature to negatively impact populations
      of free-ranging non-columbiform species, and such levels of mortality and decline
      due to an emerging infectious disease are unprecedented in British wild bird
      populations. This disease emergence event demonstrates the potential for a
      protozoan parasite to jump avian host taxonomic groups with dramatic effect over
      a short time period.

PMID- 20805870
TI  - Protein networks reveal detection bias and species consistency when analysed by
      information-theoretic methods.
AB  - We apply our recently developed information-theoretic measures for the
      characterisation and comparison of protein-protein interaction networks. These
      measures are used to quantify topological network features via macroscopic
      statistical properties. Network differences are assessed based on these
      macroscopic properties as opposed to microscopic overlap, homology information or
      motif occurrences. We present the results of a large-scale analysis of protein
      protein interaction networks. Precise null models are used in our analyses,
      allowing for reliable interpretation of the results. By quantifying the
      methodological biases of the experimental data, we can define an information
      threshold above which networks may be deemed to comprise consistent macroscopic
      topological properties, despite their small microscopic overlaps. Based on this
      rationale, data from yeast-two-hybrid methods are sufficiently consistent to
      allow for intra-species comparisons (between different experiments) and inter
      species comparisons, while data from affinity-purification mass-spectrometry
      methods show large differences even within intra-species comparisons.

PMID- 20805872
TI  - Mechanical analysis of feeding behavior in the extinct "terror bird"
      Andalgalornis steulleti (Gruiformes: Phorusrhacidae).
AB  - The South American phorusrhacid bird radiation comprised at least 18 species of
      small to gigantic terrestrial predators for which there are no close modern
      analogs. Here we perform functional analyses of the skull of the medium-sized
      (approximately 40 kg) patagornithine phorusrhacid Andalgalornis steulleti (upper
      Miocene-lower Pliocene, Andalgala Formation, Catamarca, Argentina) to assess its
      mechanical performance in a comparative context. Based on computed tomographic
      (CT) scanning and morphological analysis, the skull of Andalgalornis steulleti is
      interpreted as showing features reflecting loss of intracranial immobility.
      Discrete anatomical attributes permitting such cranial kinesis are widespread
      phorusrhacids outgroups, but this is the first clear evidence of loss of cranial
      kinesis in a gruiform bird and may be among the best documented cases among all
      birds. This apomorphic loss is interpreted as an adaptation for enhanced
      craniofacial rigidity, particularly with regard to sagittal loading. We apply a
      Finite Element approach to a three-dimensional (3D) model of the skull. Based on
      regression analysis we estimate the bite force of Andalgalornis at the bill tip
      to be 133 N. Relative to results obtained from Finite Element Analysis of one of
      its closest living relatives (seriema) and a large predatory bird (eagle), the
      phorusrhacid's skull shows relatively high stress under lateral loadings, but low
      stress where force is applied dorsoventrally (sagittally) and in "pullback"
      simulations. Given the relative weakness of the skull mediolaterally, it seems
      unlikely that Andalgalornis engaged in potentially risky behaviors that involved
      subduing large, struggling prey with its beak. We suggest that it either consumed
      smaller prey that could be killed and consumed more safely (e.g., swallowed
      whole) or that it used multiple well-targeted sagittal strikes with the beak in a
      repetitive attack-and-retreat strategy.

PMID- 20805871
TI  - Bacteria penetrate the inner mucus layer before inflammation in the dextran
      sulfate colitis model.
AB  - BACKGROUND: Protection of the large intestine with its enormous amount of
      commensal bacteria is a challenge that became easier to understand when we
      recently could describe that colon has an inner attached mucus layer devoid of
      bacteria (Johansson et al. (2008) Proc. Natl. Acad. Sci. USA 105, 15064-15069).
      The bacteria are thus kept at a distance from the epithelial cells and lack of
      this layer, as in Muc2-null mice, allow bacteria to contact the epithelium. This
      causes colitis and later on colon cancer, similar to the human disease Ulcerative
      Colitis, a disease that still lacks a pathogenetic explanation. Dextran Sulfate
      (DSS) in the drinking water is the most widely used animal model for experimental
      colitis. In this model, the inflammation is observed after 3-5 days, but early
      events explaining why DSS causes this has not been described. PRINCIPAL FINDINGS:
      When mucus formed on top of colon explant cultures were exposed to 3% DSS, the
      thickness of the inner mucus layer decreased and became permeable to 2 microm
      fluorescent beads after 15 min. Both DSS and Dextran readily penetrated the
      mucus, but Dextran had no effect on thickness or permeability. When DSS was given
      in the drinking water to mice and the colon was stained for bacteria and the Muc2
      mucin, bacteria were shown to penetrate the inner mucus layer and reach the
      epithelial cells already within 12 hours, long before any infiltration of
      inflammatory cells. CONCLUSION: DSS thus causes quick alterations in the inner
      colon mucus layer that makes it permeable to bacteria. The bacteria that reach
      the epithelial cells probably trigger an inflammatory reaction. These
      observations suggest that altered properties or lack of the inner colon mucus
      layer may be an initial event in the development of colitis.

PMID- 20805873
TI  - Antisense PMO found in dystrophic dog model was effective in cells from exon 7
      deleted DMD patient.
AB  - BACKGROUND: Antisense oligonucleotide-induced exon skipping is a promising
      approach for treatment of Duchenne muscular dystrophy (DMD). We have systemically
      administered an antisense phosphorodiamidate morpholino oligomer (PMO) targeting
      dystrophin exons 6 and 8 to a dog with canine X-linked muscular dystrophy in
      Japan (CXMD(J)) lacking exon 7 and achieved recovery of dystrophin in skeletal
      muscle. To date, however, antisense chemical compounds used in DMD animal models
      have not been directly applied to a DMD patient having the same type of exon
      deletion. We recently identified a DMD patient with an exon 7 deletion and tried
      direct translation of the antisense PMO used in dog models to the DMD patient's
      cells. METHODOLOGY/PRINCIPAL FINDINGS: We converted fibroblasts of CXMD(J) and
      the DMD patient to myotubes by FACS-aided MyoD transduction. Antisense PMOs
      targeting identical regions of dog and human dystrophin exons 6 and 8 were
      designed. These antisense PMOs were mixed and administered as a cocktail to
      either dog or human cells in vitro. In the CXMD(J) and human DMD cells, we
      observed a similar efficacy of skipping of exons 6 and 8 and a similar extent of
      dystrophin protein recovery. The accompanying skipping of exon 9, which did not
      alter the reading frame, was different between cells of these two species.
      CONCLUSION/SIGNIFICANCE: Antisense PMOs, the effectiveness of which has been
      demonstrated in a dog model, achieved multi-exon skipping of dystrophin gene on
      the FACS-aided MyoD-transduced fibroblasts from an exon 7-deleted DMD patient,
      suggesting the feasibility of systemic multi-exon skipping in humans.

PMID- 20805874
TI  - Inferring geographic coordinates of origin for Europeans using small panels of
      ancestry informative markers.
AB  - Recent large-scale studies of European populations have demonstrated the
      existence of population genetic structure within Europe and the potential to
      accurately infer individual ancestry when information from hundreds of thousands
      of genetic markers is used. In fact, when genomewide genetic variation of
      European populations is projected down to a two-dimensional Principal Components
      Analysis plot, a surprising correlation with actual geographic coordinates of
      self-reported ancestry has been reported. This substructure can hamper the search
      of susceptibility genes for common complex disorders leading to spurious
      correlations. The identification of genetic markers that can correct for
      population stratification becomes therefore of paramount importance. Analyzing
      1,200 individuals from 11 populations genotyped for more than 500,000 SNPs
      (Population Reference Sample), we present a systematic exploration of the extent
      to which geographic coordinates of origin within Europe can be predicted, with
      small panels of SNPs. Markers are selected to correlate with the top principal
      components of the dataset, as we have previously demonstrated. Performing
      thorough cross-validation experiments we show that it is indeed possible to
      predict individual ancestry within Europe down to a few hundred kilometers from
      actual individual origin, using information from carefully selected panels of 500
      or 1,000 SNPs. Furthermore, we show that these panels can be used to correctly
      assign the HapMap Phase 3 European populations to their geographic origin. The
      SNPs that we propose can prove extremely useful in a variety of different
      settings, such as stratification correction or genetic ancestry testing, and the
      study of the history of European populations.

PMID- 20805875
TI  - DNA polymerases beta and lambda mediate overlapping and independent roles in base
      excision repair in mouse embryonic fibroblasts.
AB  - Base excision repair (BER) is a DNA repair pathway designed to correct small base
      lesions in genomic DNA. While DNA polymerase beta (pol beta) is known to be the
      main polymerase in the BER pathway, various studies have implicated other DNA
      polymerases in back-up roles. One such polymerase, DNA polymerase lambda (pol
      lambda), was shown to be important in BER of oxidative DNA damage. To further
      explore roles of the X-family DNA polymerases lambda and beta in BER, we prepared
      a mouse embryonic fibroblast cell line with deletions in the genes for both pol
      beta and pol lambda. Neutral red viability assays demonstrated that pol lambda
      and pol beta double null cells were hypersensitive to alkylating and oxidizing
      DNA damaging agents. In vitro BER assays revealed a modest contribution of pol
      lambda to single-nucleotide BER of base lesions. Additionally, using co
      immunoprecipitation experiments with purified enzymes and whole cell extracts, we
      found that both pol lambda and pol beta interact with the upstream DNA
      glycosylases for repair of alkylated and oxidized DNA bases. Such interactions
      could be important in coordinating roles of these polymerases during BER.

PMID- 20805876
TI  - The non-equilibrium thermodynamics and kinetics of focal adhesion dynamics.
AB  - BACKGROUND: We consider a focal adhesion to be made up of molecular complexes,
      each consisting of a ligand, an integrin molecule, and associated plaque
      proteins. Free energy changes drive the binding and unbinding of these complexes
      and thereby controls the focal adhesion's dynamic modes of growth, treadmilling
      and resorption. PRINCIPAL FINDINGS: We have identified a competition among four
      thermodynamic driving forces for focal adhesion dynamics: (i) the work done
      during the addition of a single molecular complex of a certain size, (ii) the
      chemical free energy change associated with the addition of a molecular complex,
      (iii) the elastic free energy change associated with deformation of focal
      adhesions and the cell membrane, and (iv) the work done on a molecular
      conformational change. We have developed a theoretical treatment of focal
      adhesion dynamics as a nonlinear rate process governed by a classical kinetic
      model. We also express the rates as being driven by out-of-equilibrium
      thermodynamic driving forces, and modulated by kinetics. The mechanisms governed
      by the above four effects allow focal adhesions to exhibit a rich variety of
      behavior without the need to introduce special constitutive assumptions for their
      response. For the reaction-limited case growth, treadmilling and resorption are
      all predicted by a very simple chemo-mechanical model. Treadmilling requires
      symmetry breaking between the ends of the focal adhesion, and is achieved by
      driving force (i) above. In contrast, depending on its numerical value (ii)
      causes symmetric growth, resorption or is neutral, (iii) causes symmetric
      resorption, and (iv) causes symmetric growth. These findings hold for a range of
      conditions: temporally-constant force or stress, and for spatially-uniform and
      non-uniform stress distribution over the FA. The symmetric growth mode dominates
      for temporally-constant stress, with a reduced treadmilling regime. SIGNIFICANCE:
      In addition to explaining focal adhesion dynamics, this treatment can be coupled
      with models of cytoskeleton dynamics and contribute to the understanding of cell
      motility.

PMID- 20805877
TI  - Mechanical characterization of one-headed myosin-V using optical tweezers.
AB  - Class V myosin (myosin-V) is a cargo transporter that moves along an actin
      filament with large (approximately 36-nm) successive steps. It consists of two
      heads that each includes a motor domain and a long (23 nm) neck domain. One of
      the more popular models describing these steps, the hand-over-hand model, assumes
      the two-headed structure is imperative. However, we previously succeeded in
      observing successive large steps by one-headed myosin-V upon optimizing the angle
      of the acto-myosin interaction. In addition, it was reported that wild type
      myosin-VI and myosin-IX, both one-headed myosins, can also generate successive
      large steps. Here, we describe the mechanical properties (stepsize and stepping
      kinetics) of successive large steps by one-headed and two-headed myosin-Vs. This
      study shows that the stepsize and stepping kinetics of one-headed myosin-V are
      very similar to those of the two-headed one. However, there was a difference with
      regards to stability against load and the number of multisteps. One-headed myosin
      V also showed unidirectional movement that like two-headed myosin-V required 3.5
      k(B)T from ATP hydrolysis. This value is also similar to that of smooth muscle
      myosin-II, a non-processive motor, suggesting the myosin family uses a common
      mechanism for stepping regardless of the steps being processive or non
      processive. In this present paper, we conclude that one-headed myosin-V can
      produce successive large steps without following the hand-over-hand mechanism.

PMID- 20805878
TI  - Continued decline of malaria in The Gambia with implications for elimination.
AB  - BACKGROUND: A substantial decline in malaria was reported to have occurred over
      several years until 2007 in the western part of The Gambia, encouraging
      consideration of future elimination in this previously highly endemic region.
      Scale up of interventions has since increased with support from the Global Fund
      and other donors. METHODOLOGY/PRINCIPAL FINDINGS: We continued to examine
      laboratory records at four health facilities previously studied and investigated
      six additional facilities for a 7 year period, adding data from 243,707 slide
      examinations, to determine trends throughout the country until the end of 2009.
      We actively detected infections in a community cohort of 800 children living in
      rural villages throughout the 2008 malaria season, and assayed serological
      changes in another rural population between 2006 and 2009. Proportions of malaria
      positive slides declined significantly at all of the 10 health facilities between
      2003 (annual mean across all sites, 38.7%) and 2009 (annual mean, 7.9%).
      Statistical modelling of trends confirmed significant seasonality and decline
      over time at each facility. Slide positivity was lowest in 2009 at all sites,
      except two where lowest levels were observed in 2006. Mapping households of cases
      presenting at the latter sites in 2007-2009 indicated that these were not
      restricted to a few residual foci. Only 2.8% (22/800) of a rural cohort of
      children had a malaria episode in the 2008 season, and there was substantial
      serological decline between 2006 and 2009 in a separate rural area. CONCLUSIONS:
      Malaria has continued to decline in The Gambia, as indicated by a downward trend
      in slide positivity at health facilities, and unprecedented low incidence and
      seroprevalence in community surveys. We recommend intensification of control
      interventions for several years to further reduce incidence, prior to considering
      an elimination programme.

PMID- 20805879
TI  - Coordinated expression domains in mammalian genomes.
AB  - BACKGROUND: Gene order in eukaryotic genomes is not random. Genes showing similar
      expression (coexpression) patterns are often clustered along the genome. The goal
      of this study is to characterize coexpression clustering in mammalian genomes and
      to investigate the underlying mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: We
      detect clustering of coexpressed genes across multiple scales, from neighboring
      genes to chromosomal domains that span tens of megabases and, in some cases,
      entire chromosomes. Coexpression domains may be positively or negatively
      correlated with other domains, within and between chromosomes. We find that long
      range expression domains are associated with gene density, which in turn is
      related to physical organization of the chromosomes within the nucleus. We show
      that gene expression changes between healthy and diseased tissue samples occur in
      a gene density-dependent manner. CONCLUSIONS/SIGNIFICANCE: We demonstrate that
      coexpression domains exist across multiple scales. We identify potential
      mechanisms for short-range as well as long-range coexpression domains. We provide
      evidence that the three-dimensional architecture of the chromosomes may underlie
      long-range coexpression domains. Chromosome territory reorganization may play a
      role in common human diseases such as Alzheimer's disease and psoriasis.

PMID- 20805880
TI  - Autistic disorders and schizophrenia: related or remote? An anatomical likelihood
      estimation.
AB  - Shared genetic and environmental risk factors have been identified for autistic
      spectrum disorders (ASD) and schizophrenia. Social interaction, communication,
      emotion processing, sensorimotor gating and executive function are disrupted in
      both, stimulating debate about whether these are related conditions. Brain
      imaging studies constitute an informative and expanding resource to determine
      whether brain structural phenotype of these disorders is distinct or overlapping.
      We aimed to synthesize existing datasets characterizing ASD and schizophrenia
      within a common framework, to quantify their structural similarities. In a novel
      modification of Anatomical Likelihood Estimation (ALE), 313 foci were extracted
      from 25 voxel-based studies comprising 660 participants (308 ASD, 352 first
      episode schizophrenia) and 801 controls. The results revealed that, compared to
      controls, lower grey matter volumes within limbic-striato-thalamic circuitry were
      common to ASD and schizophrenia. Unique features of each disorder included lower
      grey matter volume in amygdala, caudate, frontal and medial gyrus for
      schizophrenia and putamen for autism. Thus, in terms of brain volumetrics, ASD
      and schizophrenia have a clear degree of overlap that may reflect shared
      etiological mechanisms. However, the distinctive neuroanatomy also mapped in each
      condition raises the question about how this is arrived in the context of common
      etiological pressures.

PMID- 20805881
TI  - Structural insights into the quinolone resistance mechanism of Mycobacterium
      tuberculosis DNA gyrase.
AB  - Mycobacterium tuberculosis DNA gyrase, an indispensable nanomachine involved in
      the regulation of DNA topology, is the only type II topoisomerase present in this
      organism and is hence the sole target for quinolone action, a crucial drug active
      against multidrug-resistant tuberculosis. To understand at an atomic level the
      quinolone resistance mechanism, which emerges in extensively drug resistant
      tuberculosis, we performed combined functional, biophysical and structural
      studies of the two individual domains constituting the catalytic DNA gyrase
      reaction core, namely the Toprim and the breakage-reunion domains. This allowed
      us to produce a model of the catalytic reaction core in complex with DNA and a
      quinolone molecule, identifying original mechanistic properties of quinolone
      binding and clarifying the relationships between amino acid mutations and
      resistance phenotype of M. tuberculosis DNA gyrase. These results are compatible
      with our previous studies on quinolone resistance. Interestingly, the structure
      of the entire breakage-reunion domain revealed a new interaction, in which the
      Quinolone-Binding Pocket (QBP) is blocked by the N-terminal helix of a symmetry
      related molecule. This interaction provides useful starting points for designing
      peptide based inhibitors that target DNA gyrase to prevent its binding to DNA.

PMID- 20805882
TI  - Periostin associates with Notch1 precursor to maintain Notch1 expression under a
      stress condition in mouse cells.
AB  - BACKGROUND: Matricellular proteins, including periostin, modulate cell-matrix
      interactions and cell functions by acting outside of cells. METHODS AND FINDINGS:
      In this study, however, we reported that periostin physically associates with the
      Notch1 precursor at its EGF repeats in the inside of cells. Moreover, by using
      the periodontal ligament of molar from periostin-deficient adult mice (Pn-/-
      molar PDL), which is a constitutively mechanically stressed tissue, we found that
      periostin maintained the site-1 cleaved 120-kDa transmembrane domain of Notch1
      (N1) level without regulating Notch1 mRNA expression. N1 maintenance in vitro was
      also observed under such a stress condition as heat and H(2)O(2) treatment in
      periostin overexpressed cells. Furthermore, we found that the expression of a
      downstream effector of Notch signaling, Bcl-xL was decreased in the Pn-/- molar
      PDL, and in the molar movement, cell death was enhanced in the pressure side of
      Pn-/- molar PDL. CONCLUSION: These results suggest the possibility that periostin
      inhibits cell death through up-regulation of Bcl-xL expression by maintaining the
      Notch1 protein level under the stress condition, which is caused by its physical
      association with the Notch1 precursor.

PMID- 20805883
TI  - Microarray-based approach identifies differentially expressed microRNAs in
      porcine sexually immature and mature testes.
AB  - BACKGROUND: MicroRNAs (miRNAs) are short non-coding RNA molecules which are
      proved to be involved in mammalian spermatogenesis. Their expression and function
      in the porcine germ cells are not fully understood. METHODOLOGY: We employed a
      miRNA microarray containing 1260 unique miRNA probes to evaluate the miRNA
      expression patterns between sexually immature (60-day) and mature (180-day) pig
      testes. One hundred and twenty nine miRNAs representing 164 reporter miRNAs were
      expressed differently (p<0.1). Fifty one miRNAs were significantly up-regulated
      and 78 miRNAs were down-regulated in mature testes. Nine of these differentially
      expressed miRNAs were validated using quantitative RT-PCR assay. Totally 15,919
      putative miRNA-target sites were detected by using RNA22 method to align 445 NCBI
      pig cDNA sequences with these 129 differentially expressed miRNAs, and seven
      putative target genes involved in spermatogenesis including DAZL, RNF4 gene were
      simply confirmed by quantitative RT-PCR. CONCLUSIONS: Overall, the results of
      this study indicated specific miRNAs expression in porcine testes and suggested
      that miRNAs had a role in regulating spermatogenesis.

PMID- 20805884
TI  - Mesenchymal stem cell therapy regenerates the native bone-tendon junction after
      surgical repair in a degenerative rat model.
AB  - BACKGROUND: The enthesis, which attaches the tendon to the bone, naturally
      disappears with aging, thus limiting joint mobility. Surgery is frequently needed
      but the clinical outcome is often poor due to the decreased natural healing
      capacity of the elderly. This study explored the benefits of a treatment based on
      injecting chondrocyte and mesenchymal stem cells (MSC) in a new rat model of
      degenerative enthesis repair. METHODOLOGY: The Achilles' tendon was cut and the
      enthesis destroyed. The damage was repaired by classical surgery without cell
      injection (group G1, n = 52) and with chondrocyte (group G2, n = 51) or MSC
      injection (group G3, n = 39). The healing rate was determined macroscopically 15,
      30 and 45 days later. The production and organization of a new enthesis was
      assessed by histological scoring of collagen II immunostaining, glycoaminoglycan
      production and the presence of columnar chondrocytes. The biomechanical load
      required to rupture the bone-tendon junction was determined. PRINCIPAL FINDINGS:
      The spontaneous healing rate in the G1 control group was 40%, close to those
      observed in humans. Cell injection significantly improved healing (69%, p =
      0.0028 for G2 and p = 0.006 for G3) and the load-to-failure after 45 days
      (p<0.05) over controls. A new enthesis was clearly produced in cell-injected G2
      and G3 rats, but not in the controls. Only the MSC-injected G3 rats had an
      organized enthesis with columnar chondrocytes as in a native enthesis 45 days
      after surgery. CONCLUSIONS: Cell therapy is an efficient procedure for
      reconstructing degenerative entheses. MSC treatment produced better organ
      regeneration than chondrocyte treatment. The morphological and biomechanical
      properties were similar to those of a native enthesis.

PMID- 20805885
TI  - Apparent non-canonical trans-splicing is generated by reverse transcriptase in
      vitro.
AB  - BACKGROUND: Trans-splicing, the in vivo joining of two independently transcribed
      RNA molecules, is well characterized in lower eukaryotes, but was long thought
      absent from metazoans. However, recent bioinformatic analyses of EST sequences
      suggested widespread trans-splicing in mammals. These apparently spliced
      transcripts generally lacked canonical splice sites, leading us to question their
      authenticity. Particularly, the native ability of reverse transcriptase enzymes
      to template switch during transcription could produce apparently trans-spliced
      sequences. PRINCIPAL FINDINGS: Here we report an in vitro system for the analysis
      of template switching in reverse transcription. Using highly purified RNA
      substrates, we show the reproducible occurrence of apparent trans-splicing
      between two RNA molecules. Other reported non-canonical splicing events such as
      exon shuffling and sense-antisense fusions were also readily detected. The latter
      caused the production of apparent antisense non-coding RNAs, which are also
      reported to be abundant in humans. CONCLUSIONS: We propose that most reported
      examples of non-canonical splicing in metazoans arise through template switching
      by reverse transcriptase during cDNA preparation. We further show that the
      products of template switching can vary between reverse transcriptases, providing
      a simple diagnostic for identifying many of these experimental artifacts.

PMID- 20805886
TI  - Unique DNA repair gene variations and potential associations with the primary
      antibody deficiency syndromes IgAD and CVID.
AB  - BACKGROUND: Despite considerable effort, the genetic factors responsible for >90%
      of the antibody deficiency syndromes IgAD and CVID remain elusive. To produce a
      functionally diverse antibody repertoire B lymphocytes undergo class switch
      recombination. This process is initiated by AID-catalyzed deamination of cytidine
      to uridine in switch region DNA. Subsequently, these residues are recognized by
      the uracil excision enzyme UNG2 or the mismatch repair proteins MutSalpha
      (MSH2/MSH6) and MutLalpha (PMS2/MLH1). Further processing by ubiquitous DNA
      repair factors is thought to introduce DNA breaks, ultimately leading to class
      switch recombination and expression of a different antibody isotype.
      METHODOLOGY/PRINCIPAL FINDINGS: Defects in AID and UNG2 have been shown to result
      in the primary immunodeficiency hyper-IgM syndrome, leading us to hypothesize
      that additional, potentially more subtle, DNA repair gene variations may underlie
      the clinically related antibody deficiencies syndromes IgAD and CVID. In a survey
      of twenty-seven candidate DNA metabolism genes, markers in MSH2, RAD50, and RAD52
      were associated with IgAD/CVID, prompting further investigation into these
      pathways. Resequencing identified four rare, non-synonymous alleles associated
      with IgAD/CVID, two in MLH1, one in RAD50, and one in NBS1. One IgAD patient
      carried heterozygous non-synonymous mutations in MLH1, MSH2, and NBS1. Functional
      studies revealed that one of the identified mutations, a premature RAD50 stop
      codon (Q372X), confers increased sensitivity to ionizing radiation. CONCLUSIONS:
      Our results are consistent with a class switch recombination model in which AID
      catalyzed uridines are processed by multiple DNA repair pathways. Genetic defects
      in these DNA repair pathways may contribute to IgAD and CVID.

PMID- 20805888
TI  - The protease inhibitor alpha-2-macroglobulin-like-1 is the p170 antigen
      recognized by paraneoplastic pemphigus autoantibodies in human.
AB  - BACKGROUND: Paraneoplastic pemphigus (PNP) is a devastating autoimmune blistering
      disease, involving mucocutaneous and internal organs, and associated with
      underlying neoplasms. PNP is characterized by the production of autoantibodies
      targeting proteins of the plakin and cadherin families involved in maintenance of
      cell architecture and tissue cohesion. Nevertheless, the identity of an antigen
      of Mr 170,000 (p170), thought to be critical in PNP pathogenesis, has remained
      unknown. METHODOLOGY/PRINCIPAL FINDINGS: Using an immunoprecipitation and mass
      spectrometry based approach, we identified p170 as alpha-2-macroglobuline-like-1,
      a broad range protease inhibitor expressed in stratified epithelia and other
      tissues damaged in the PNP disease course. We demonstrate that 10 PNP sera
      recognize alpha-2-macroglobuline-like-1 (A2ML1), while none of the control sera
      obtained from patients with bullous pemphigoid, pemphigus vulgaris, pemphigus
      foliaceus and normal subjects does. CONCLUSIONS/SIGNIFICANCE: Our study unravels
      a broad range protease inhibitor as a new class of target antigens in a
      paraneoplastic autoimmune multiorgan syndrome and opens a new challenging
      investigation avenue for a better understanding of PNP pathogenesis.

PMID- 20805887
TI  - Selenoproteins are essential for proper keratinocyte function and skin
      development.
AB  - Dietary selenium is known to protect skin against UV-induced damage and cancer
      and its topical application improves skin surface parameters in humans, while
      selenium deficiency compromises protective antioxidant enzymes in skin.
      Furthermore, skin and hair abnormalities in humans and rodents may be caused by
      selenium deficiency, which are overcome by dietary selenium supplementation. Most
      important biological functions of selenium are attributed to selenoproteins,
      proteins containing selenium in the form of the amino acid, selenocysteine (Sec).
      Sec insertion into proteins depends on Sec tRNA; thus, knocking out the Sec tRNA
      gene (Trsp) ablates selenoprotein expression. We generated mice with targeted
      removal of selenoproteins in keratin 14 (K14) expressing cells and their
      differentiated descendents. The knockout progeny had a runt phenotype, developed
      skin abnormalities and experienced premature death. Lack of selenoproteins in
      epidermal cells led to the development of hyperplastic epidermis and aberrant
      hair follicle morphogenesis, accompanied by progressive alopecia after birth.
      Further analyses revealed that selenoproteins are essential antioxidants in skin
      and unveiled their role in keratinocyte growth and viability. This study links
      severe selenoprotein deficiency to abnormalities in skin and hair and provides
      genetic evidence for the role of these proteins in keratinocyte function and
      cutaneous development.

PMID- 20805889
TI  - Persistence of different forms of transient RNAi during apoptosis in mammalian
      cells.
AB  - Gene silencing by transient or stable RNA-interference (RNAi) is used for the
      study of apoptosis with an assumption that apoptotic events will not influence
      RNAi. However, we recently reported that stable RNAi, i.e., a permanent gene
      knockdown mediated by shRNA-generating DNA vectors that are integrated in the
      genome, fails rapidly after induction of apoptosis due to caspase-3-mediated
      cleavage and inactivation of the endoribonuclease Dicer-1 that is required for
      conversion of shRNA to siRNA. Since apoptosis studies also increasingly employ
      transient RNAi models in which apoptosis is induced immediately after a gene is
      temporarily knocked down within a few days of transfection with RNAi-inducing
      agents, we examined the impact of apoptosis on various models of transient RNAi.
      We report here that unlike the stable RNAi, all forms of transient RNAi, whether
      Dicer-1-independent (by 21mer dsRNA) or Dicer-1-dependent (by 27mer dsRNA or
      shRNA-generating DNA vector), whether for an exogenous gene GFP or an endogenous
      gene poly(ADP-ribose) polymerase-1, do not fail for 2-3 days after onset of
      apoptosis. Our results reflect the differences in dynamics of achieving and
      maintaining RNAi during the early phase after transfection in the transient RNAi
      model and the late steady-state phase of gene-knockdown in stable RNAi model. Our
      results also sound a cautionary note that RNAi status should be frequently
      validated in the studies involving apoptosis and that while stable RNAi can be
      safely used for the study of early apoptotic events, transient RNAi is more
      suitable for the study of both early and late apoptotic events.

PMID- 20805890
TI  - Impact of the AHI1 gene on the vulnerability to schizophrenia: a case-control
      association study.
AB  - BACKGROUND: The Abelson helper integration-1 (AHI1) gene is required for both
      cerebellar and cortical development in humans. While the accelerated evolution of
      AHI1 in the human lineage indicates a role in cognitive (dys)function, a linkage
      scan in large pedigrees identified AHI1 as a positional candidate for
      schizophrenia. To further investigate the contribution of AHI1 to the
      susceptibility of schizophrenia, we evaluated the effect of AHI1 variation on the
      vulnerability to psychosis in two samples from Spain and Germany.
      METHODOLOGY/PRINCIPAL FINDINGS: 29 single-nucleotide polymorphisms (SNPs) located
      in a genomic region including the AHI1 gene were genotyped in two samples from
      Spain (280 patients with psychotic disorders; 348 controls) and Germany (247
      patients with schizophrenic disorders; 360 controls). Allelic, genotypic and
      haplotype frequencies were compared between cases and controls in both samples
      separately, as well as in the combined sample. The effect of genotype on several
      psychopathological measures (BPRS, KGV, PANSS) assessed in a Spanish subsample
      was also evaluated. We found several significant associations in the Spanish
      sample. Particularly, rs7750586 and rs911507, both located upstream of the AHI1
      coding region, were found to be associated with schizophrenia in the analysis of
      genotypic (p = 0.0033, and 0.031, respectively) and allelic frequencies (p =
      0.001 in both cases). Moreover, several other risk and protective haplotypes were
      detected (0.006<p<0.036). Joint analysis also supported the association of
      rs7750586 and rs911507 with the risk for schizophrenia. The analysis of clinical
      measures also revealed an effect on symptom severity (minimum P value = 0.0037).
      CONCLUSIONS/SIGNIFICANCE: Our data support, in agreement with previous reports,
      an effect of AHI1 variation on the susceptibility to schizophrenia in central and
      southern European populations.

PMID- 20805892
TI  - jsPhyloSVG: a javascript library for visualizing interactive and vector-based
      phylogenetic trees on the web.
AB  - BACKGROUND: Many software packages have been developed to address the need for
      generating phylogenetic trees intended for print. With an increased use of the
      web to disseminate scientific literature, there is a need for phylogenetic trees
      to be viewable across many types of devices and feature some of the interactive
      elements that are integral to the browsing experience. We propose a novel
      approach for publishing interactive phylogenetic trees. METHODS/PRINCIPAL
      FINDINGS: We present a javascript library, jsPhyloSVG, which facilitates
      constructing interactive phylogenetic trees from raw Newick or phyloXML formats
      directly within the browser in Scalable Vector Graphics (SVG) format. It is
      designed to work across all major browsers and renders an alternative format for
      those browsers that do not support SVG. The library provides tools for building
      rectangular and circular phylograms with integrated charting. Interactive
      features may be integrated and made to respond to events such as clicks on any
      element of the tree, including labels. CONCLUSIONS/SIGNIFICANCE: jsPhyloSVG is an
      open-source solution for rendering dynamic phylogenetic trees. It is capable of
      generating complex and interactive phylogenetic trees across all major browsers
      without the need for plugins. It is novel in supporting the ability to interpret
      the tree inference formats directly, exposing the underlying markup to data
      mining services. The library source code, extensive documentation and live
      examples are freely accessible at www.jsphylosvg.com.

PMID- 20805893
TI  - LRCH proteins: a novel family of cytoskeletal regulators.
AB  - BACKGROUND: Comparative genomics has revealed an unexpected level of conservation
      for gene products across the evolution of animal species. However, the molecular
      function of only a few proteins has been investigated experimentally, and the
      role of many animal proteins still remains unknown. Here we report the
      characterization of a novel family of evolutionary conserved proteins, which
      display specific features of cytoskeletal scaffolding proteins, referred to as
      LRCHs. PRINCIPAL FINDINGS: Taking advantage of the existence of a single LRCH
      gene in flies, dLRCH, we explored its function in cultured cells, and show that
      dLRCH act to stabilize the cell cortex during cell division. dLRCH depletion
      leads to ectopic cortical blebs and alters positioning of the mitotic spindle. We
      further examined the consequences of dLRCH deletion throughout development and
      adult life. Although dLRCH is not essential for cell division in vivo, flies
      lacking dLRCH display a reduced fertility and fitness, particularly when raised
      at extreme temperatures. CONCLUSION/SIGNIFICANCE: These results support the idea
      that some cytoskeletal regulators are important to buffer environmental
      variations and ensure the proper execution of basic cellular processes, such as
      the control of cell shape, under environmental variations.

PMID- 20805895
TI  - Augmentation and combination strategies to treat the residual symptoms of major
      depressive disorder.

PMID- 20805896
TI  - What Treatments are Prescribed for Posttraumatic Stress Disorder?

PMID- 20805894
TI  - Gliadin peptide P31-43 localises to endocytic vesicles and interferes with their
      maturation.
AB  - BACKGROUND: Celiac Disease (CD) is both a frequent disease (1:100) and an
      interesting model of a disease induced by food. It consists in an immunogenic
      reaction to wheat gluten and glutenins that has been found to arise in a specific
      genetic background; however, this reaction is still only partially understood.
      Activation of innate immunity by gliadin peptides is an important component of
      the early events of the disease. In particular the so-called "toxic" A-gliadin
      peptide P31-43 induces several pleiotropic effects including Epidermal Growth
      Factor Receptor (EGFR)-dependent actin remodelling and proliferation in cultured
      cell lines and in enterocytes from CD patients. These effects are mediated by
      delayed EGFR degradation and prolonged EGFR activation in endocytic vesicles. In
      the present study we investigated the effects of gliadin peptides on the
      trafficking and maturation of endocytic vesicles. METHODS/PRINCIPAL FINDINGS:
      Both P31-43 and the control P57-68 peptide labelled with fluorochromes were found
      to enter CaCo-2 cells and interact with the endocytic compartment in pulse and
      chase, time-lapse, experiments. P31-43 was localised to vesicles carrying early
      endocytic markers at time points when P57-68-carrying vesicles mature into late
      endosomes. In time-lapse experiments the trafficking of P31-43-labelled vesicles
      was delayed, regardless of the cargo they were carrying. Furthermore in celiac
      enterocytes, from cultured duodenal biopsies, P31-43 trafficking is delayed in
      early endocytic vesicles. A sequence similarity search revealed that P31-43 is
      strikingly similar to Hrs, a key molecule regulating endocytic maturation. A
      gliadin peptide P31-43 interfered with Hrs correct localisation to early
      endosomes as revealed by western blot and immunofluorescence microscopy.
      CONCLUSIONS: P31-43 and P57-68 enter cells by endocytosis. Only P31-43 localises
      at the endocytic membranes and delays vesicle trafficking by interfering with Hrs
      mediated maturation to late endosomes in cells and intestinal biopsies.
      Consequently, in P31-43-treated cells, Receptor Tyrosine Kinase (RTK) activation
      is extended. This finding may explain the role played by gliadin peptides in
      inducing proliferation and other effects in enterocytes from CD biopsies.

PMID- 20805897
TI  - The Five C's of Confidentiality and How to DEAL with Them.

PMID- 20805898
TI  - Sad dads: paternal postpartum depression.
AB  - The postpartum period is associated with many adjustments to fathers that pose
      risks for depression. Estimates of the prevalence of paternal postpartum
      depression (PPD) in the first two months postpartum vary in the postpartum period
      from 4 to 25 percent. Paternal PPD has high comorbidity with maternal PPD and
      might also be associated with other postpartum psychiatric disorders. Studies so
      far have only used diagnostic criteria for maternal PPD to investigate paternal
      PPD, so there is an urgent need to study the validity of these scales for men and
      develop accurate diagnostic tools for paternal PPD. Paternal PPD has negative
      impacts on family, including increasing emotional and behavioral problems among
      their children (either directly or through the mother) and increasing conflicts
      in the marital relationship. Changes in hormones, including testosterone,
      estrogen, cortisol, vasopressin, and prolactin, during the postpartum period in
      fathers may be biological risk factors in paternal PPD. Fathers who have
      ecological risk factors, such as excessive stress from becoming a parent, lack of
      social supports for parenting, and feeling excluded from mother-infant bonding,
      may be more likely to develop paternal PPD. Support from their partner,
      educational programs, policy for paid paternal leave, as well as consideration of
      psychiatric care may help fathers cope with stressful experiences during the
      postpartum period.

PMID- 20805899
TI  - An overview of filicide.
AB  - Filicide, or the murder of one's own child, is an unfathomable crime. With Andrea
      Yates's return to trial in the summer of 2006, filicide once again came to the
      forefront of psychiatric issues in the media. One positive outcome that may be
      derived from this tragedy is practitioners' heightened awareness that parents
      may, for a variety of reasons, be compelled to kill their children. This article
      aims to educate mental health providers about the concept of filicide by
      presenting a broad overview of the topic, including a discussion of its history,
      definitions, classifications, outcomes, and the research surrounding it. This
      knowledge will hopefully bring about clinicians' increased exploration of
      patients' thoughts of harming their children, which may ultimately lead to the
      prevention of these senseless crimes.

PMID- 20805900
TI  - A randomized, controlled trial of disease management modules, including
      telepsychiatric care, for depression in rural primary care.
AB  - Introduction. Disease management modules (DMM), including education, tracking,
      support, and medical care, have improved health for patients with asthma and
      diabetes. For rural patients, novel ways of delivery are needed to access
      clinical expertise from urban or academic specialists. Telemedicine (telephone
      and televideo) could be instrumental in this process, though no randomized,
      controlled trials have assessed their effectiveness.Methods. Self-report and
      structured psychiatric interviews were used to screen potential depressed
      subjects. Subjects were randomized to: 1) usual care with a DMM using telephone
      and self-report questionnaires; or 2) a DMM using telephone, questionnaires, and
      monthly televideo psychiatric consultation emphasizing primary care physician
      (PCP) skill development. Subjects' depressive symptoms, health status, and
      satisfaction with care were tabulated at three, six, and 12 months after study
      entry.Results. There was significant clinical improvement for depression in both
      groups, with a trend toward significance in the more intensive module.
      Satisfaction and retention was superior in the more intensive group. There was no
      overall change in health functioning in either group.Conclusions. Intensive
      modules using telepsychiatric educational interventions toward PCPs may be
      superior, but the most critical ingredient may be administrative tracking of
      patients, prompted intervention by PCPs, and (when necessary) new ideas by a
      specialist.

PMID- 20805901
TI  - Dissociation During Intense Military Stress is Related to Subsequent Somatic
      Symptoms in Women.
AB  - BACKGROUND: Research studies of the female response to intense stress are under
      represented in the scientific literature; indeed, publications in female humans
      and animals number half those in male subjects. In addition, women have only
      recently entered more dangerous professions that were historically limited to
      men. The US Navy's survival course, therefore, offers a unique opportunity to
      examine, in a controlled manner, individual differences in the human female
      response to acute and realistic military stress. METHOD: The current study
      assessed the nature and prevalence of dissociative symptoms and other aspects of
      adaptive function in healthy female subjects experiencing acute, intense stress
      during US Navy survival training. Cognitive dissociation and previous exposure to
      traumatic events were assessed at baseline in 32 female service members prior to
      Navy survival training. At the conclusion of training, retrospectively rated
      levels of dissociation during peak training stress and current health symptoms
      were assessed. RESULTS: Female subjects reported previous trauma (35%) and at
      least one symptom of dissociation at baseline prior to training (47%). Eighty
      eight percent of subjects reported experiencing multiple symptoms of dissociation
      during peak training stress. Post-stress dissociation scores and stress-induced
      increases in dissociation, as well as prior cumulative exposure to potentially
      traumatic events, were significant predictors of post-stress health symptoms.
      DISCUSSION: In this study, increases in dissociative symptoms during intense
      training stress, post-stress dissociation symptom levels, and prior cumulative
      exposure to stressful, potentially traumatic events predicted post-stress health
      symptoms in women. Prior studies in men have demonstrated correlations between
      neurobiological responses to stress and stress-associated levels of dissociation.
      Thus future studies in larger samples of women are needed to investigate the
      relationship between prior stress exposure, alterations in neurobiological
      responses to stress and potentially related alterations in neuropsychological and
      physical reactions to stress.

PMID- 20805902
TI  - Increase the dose or give it a few more weeks.

PMID- 20805903
TI  - Increase the dose or give it a few more weeks.

PMID- 20805904
TI  - Prescribing for buprenorphine in the treatment of opioid addiction.

PMID- 20805905
TI  - Borderline personality disorder and the bipolar disorder spectrum.

PMID- 20805906
TI  - Time to feel good: the therapeutic time course of antidepressants.

PMID- 20805907
TI  - Physician and medical student stress.

PMID- 20805908
TI  - Using daily interactive voice response assessments: to measure onset of symptom
      improvement with duloxetine.
AB  - Most clinical trials measure patient responses weekly, requiring patients to
      accurately recall and report their symptoms from the previous six days. More
      frequent assessments would be less susceptible to recall errors and recency
      effects as weekly assessments, but increased office visits burden clinicians and
      patients and can lead to higher attrition or non compliance. Interactive voice
      response (IVR) technology permits data collection at greater frequencies with
      minimal reporting burdens. An ancillary study within a randomized clinical trial
      evaluated the use of IVR to gather measures of patients' ratings of emotional and
      painful symptoms of depression on a daily basis. Unmedicated patients randomized
      to a starting dose of duloxetine of 30 mg QD (n=67) or 60 mg QD (n=70) called an
      IVR system daily to complete Verbal Numeric Scales for pain and Patient Global
      Impression of Improvement for both physical and emotional changes. Patients'
      compliance with daily IVR assessments was examined, and the IVR data obtained
      showed that patients started at 60 mg reported less pain and greater physical and
      emotional improvements than patients started at 30 mg. Dose related differences
      were evident as early as one day after the start treatment. This study provides
      new data about the usefulness of daily IVR assessments in clinical research and
      supports other studies regarding early symptom improvement with duloxetine.

PMID- 20805909
TI  - Anchoring perceptions of clinical change on accurate recollection of the past:
      memory enhanced retrospective evaluation of treatment (MERET).
AB  - OBJECTIVE: To evaluate patients' self-reports of treatment efficacy with and
      without self-prompted memory aids regarding their clinical experiences obtained
      prior to treatment initiation. DESIGN: Double-blind, placebo-controlled trial
      with variable expected duration placebo lead-in and washout. SETTING: Multisite
      (US) randomized clinical trial. PARTICIPANTS: Seventy-four patients with initial
      or recurrent DSM-IV diagnosis of major depression with symptoms of at least four
      weeks duration. A minimum Clinical Global Impression of Severity rating of
      Moderately Depressed and a clinician 17-item Hamilton Rating Scale for Depression
      score of 15 or greater, with the depressed mood item score of at least 2 were
      required for study entry. MEASUREMENTS: Patient global impression of improvement
      (PGI-I) ratings obtained using an interactive voice response (IVR) computer
      automated telephone system prior to and following playback of impromptu patient
      recordings obtained prior to the start of treatment (MERET). RESULTS: MERET PGI-I
      ratings differentiated the effects of drug treatment from placebo more
      effectively than did standard PGI-I ratings. The drug-placebo treatment effect
      size obtained using standard PGI-I ratings was 0.525, whereas the effect size
      with MERET PGI-I ratings was 0.612. CONCLUSION: The enhanced drug-placebo
      separation appeared to be primarily due to increased patients' perceptions of
      drug treatment effectiveness. Patients perceiving the greatest degree of clinical
      improvement indicated more benefit from hearing the MERET recordings. MERET
      appears to be a viable method for enhancing patients' insights into the benefits
      of effective treatments by allowing them to use personal descriptions provided in
      their own words and voice.

PMID- 20805911
TI  - Informed consent and competency: doctor's dilemma on the consultation liaison
      service.
AB  - With the increase in morbidity in the mentally ill, we also see an increase in
      the number of consultation requests from the medical and surgical departments to
      the psychiatric consultation team. Beside the classic questions of managing
      depression, psychosis, or agitation, psychiatrists are facing questions regarding
      patient competency. This usually refers to the patient's ability to consent to or
      refuse medical treatment, to be discharged against medical advice, or the
      patient's capacity to live independently and manage his or her own finances. In
      this article, the principles of informed consent and decision-making capacity
      will be reviewed, as well as the legal cases pertaining to these issues. A brief
      review of the existing literature will be summarized.

PMID- 20805910
TI  - Clinical manifestations, diagnosis, and empirical treatments for catatonia.
AB  - OBJECTIVE: Review the medical literature on the history and clinical features of
      catatonia so as to provide a contemporary clinical guide for successfully
      diagnosing and treating the various clinical forms of catatonia. DESIGN: RESULTS
      of MEDLINE computerized searches using search terms 'catatonia', 'treatment of
      catatonia', 'electroconvulsive therapy and catatonia', 'benzodiazepines and
      catatonia', clinical case reports, and book chapters covering the medical and
      psychiatric literature relevant to catatonia and its associated treatments were
      examined. SETTING: Academic medical center. PARTICIPANTS: None. MEASUREMENTS:
      None. RESULTS: Catatonia is a common but under-recognized clinical syndrome. No
      large-scale, controlled studies exist to determine the relative effectiveness of
      current treatments, including sedative-hypnotic medications (benzodiazepines or
      barbiturates), and electroconvulsive therapy (ECT). CONCLUSION: Despite the lack
      of large-scale, controlled studies, benzodiazepines appear to be an effective
      first-line treatment for catatonia. ECT is now often reserved as a second-line
      treatment despite more than 60 years of documented efficacy and safety. However,
      ECT should be viewed as a first-line intervention in cases of severe or malignant
      catatonias.

PMID- 20805891
TI  - Cancer biomarker discovery: the entropic hallmark.
AB  - BACKGROUND: It is a commonly accepted belief that cancer cells modify their
      transcriptional state during the progression of the disease. We propose that the
      progression of cancer cells towards malignant phenotypes can be efficiently
      tracked using high-throughput technologies that follow the gradual changes
      observed in the gene expression profiles by employing Shannon's mathematical
      theory of communication. Methods based on Information Theory can then quantify
      the divergence of cancer cells' transcriptional profiles from those of normally
      appearing cells of the originating tissues. The relevance of the proposed methods
      can be evaluated using microarray datasets available in the public domain but the
      method is in principle applicable to other high-throughput methods.
      METHODOLOGY/PRINCIPAL FINDINGS: Using melanoma and prostate cancer datasets we
      illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon
      divergence to trace the transcriptional changes progression of the disease. We
      establish how the variations of these two measures correlate with established
      biomarkers of cancer progression. The Information Theory measures allow us to
      identify novel biomarkers for both progressive and relatively more sudden
      transcriptional changes leading to malignant phenotypes. At the same time, the
      methodology was able to validate a large number of genes and processes that seem
      to be implicated in the progression of melanoma and prostate cancer.
      CONCLUSIONS/SIGNIFICANCE: We thus present a quantitative guiding rule, a new
      unifying hallmark of cancer: the cancer cell's transcriptome changes lead to
      measurable observed transitions of Normalized Shannon Entropy values (as measured
      by high-throughput technologies). At the same time, tumor cells increment their
      divergence from the normal tissue profile increasing their disorder via creation
      of states that we might not directly measure. This unifying hallmark allows, via
      the the Jensen-Shannon divergence, to identify the arrow of time of the processes
      from the gene expression profiles, and helps to map the phenotypical and
      molecular hallmarks of specific cancer subtypes. The deep mathematical basis of
      the approach allows us to suggest that this principle is, hopefully, of general
      applicability for other diseases.

PMID- 20805912
TI  - Antidepressants in bipolar disorder.

PMID- 20805913
TI  - Real-world Data on Atypical Antipsychotic Medication Side Effects.
AB  - In this article, we provide information on patient-reported side effects from a
      cross-section of real-world patients. Specifically, data on side effects were
      tabulated for patients taking at least one of the following atypical
      antipsychotic medications: aripiprazole, olanzapine, paliperidone, quetiapine,
      risperidone, or ziprasidone. Approximately 54 percent of the 353 respondents
      reported having experienced a side effect as a result of taking an atypical
      antipsychotic medication. Most common side effects mentioned included the
      following: weight gain/hunger, tiredness/lethargy, and lack of
      coordination/muscle problems, such as tenderness, twitches, and tremors. Of those
      experiencing a side effect, less than 25 percent reported this side effect to
      their physician.

PMID- 20805914
TI  - Road Rage: What's Driving It?
AB  - Up to one-third of community participants report being perpetrators of road rage,
      indicating that various forms of road rage are relatively commonplace. However,
      only two percent or less of incidents culminate in serious damage to persons or
      vehicles. The most common offenders appear to be young and male. A number of
      factors may contribute to road rage, including environmental factors (e.g.,
      greater number of miles driven per day, traffic density), nonspecific
      psychological factors (e.g., displaced aggression, attribution of blame to
      others), and bona fide Axis I and II disorders. The most common Axis I disorders
      appear to be related to alcohol and substance misuse, whereas possible Axis II
      disorders include borderline and antisocial personality disorders. Being aware of
      these contributory factors to road rage may improve general clinical awareness of
      the nature and treatment of perpetrators.

PMID- 20805915
TI  - The Bereavement Exclusion for the Diagnosis of Major Depression: To be, or not to
      be.
AB  - This paper reviews studies bearing on the validity of the bereavement exclusion
      for the diagnosis of major depression. It concludes that the exclusion is not
      supported by the best available data, and the authors propose revisions for
      Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition.

PMID- 20805916
TI  - The 4-Item Negative Symptom Assessment (NSA-4) Instrument: A Simple Tool for
      Evaluating Negative Symptoms in Schizophrenia Following Brief Training.
AB  - Objective. To assess the ability of mental health professionals to use the 4-item
      Negative Symptom Assessment instrument, derived from the Negative Symptom
      Assessment-16, to rapidly determine the severity of negative symptoms of
      schizophrenia.Design. Open participation.Setting. Medical education
      conferences.Participants. Attendees at two international psychiatry
      conferences.Measurements. Participants read a brief set of the 4-item Negative
      Symptom Assessment instructions and viewed a videotape of a patient with
      schizophrenia. Using the 1 to 6 4-item Negative Symptom Assessment severity
      rating scale, they rated four negative symptom items and the overall global
      negative symptoms. These ratings were compared with a consensus rating
      determination using frequency distributions and Chi-square tests for the
      proportion of participant ratings that were within one point of the expert
      rating.Results. More than 400 medical professionals (293 physicians, 50% with a
      European practice, and 55% who reported past utilization of schizophrenia ratings
      scales) participated. Between 82.1 and 91.1 percent of the 4-items and the global
      rating determinations by the participants were within one rating point of the
      consensus expert ratings. The differences between the percentage of participant
      rating scores that were within one point versus the percentage that were greater
      than one point different from those by the consensus experts was significant
      (p<0.0001). Participants rating of negative symptoms using the 4-item Negative
      Symptom Assessment did not generally differ among the geographic regions of
      practice, the professional credentialing, or their familiarity with the use of
      schizophrenia symptom rating instruments.Conclusion. These findings suggest that
      clinicians from a variety of geographic practices can, after brief training, use
      the 4-item Negative Symptom Assessment effectively to rapidly assess negative
      symptoms in patients with schizophrenia.

PMID- 20805917
TI  - An archetype of the collaborative efforts of psychotherapy and psychopharmacology
      in successfully treating dissociative identity disorder with comorbid bipolar
      disorder.
AB  - We present a case where dissociative identity disorder was effectively treated
      with memory retrieval psychotherapy. However, the patient's comorbid bipolar
      disorder contributed to the patient's instability and fortified the amnesiac
      barriers that exist between alter personality states in dissociative identity
      disorder, which made memory retrieval difficult to achieve. Implications from
      this case indicate that a close collaboration between psychologist and
      psychiatrist focused on carefully diagnosing and treating existing comorbid
      conditions may be the most important aspect in treating dissociative identity
      disorder. We present our experience of successfully treating a patient with
      dissociative identity disorder and bipolar disorder using this collaborative
      method.

PMID- 20805918
TI  - Gait and its assessment in psychiatry.
AB  - Gait reflects all levels of nervous system function. In psychiatry, gait
      disturbances reflecting cortical and subcortical dysfunction are often seen.
      Observing spontaneous gait, sometimes augmented by a few brief tests, can be
      highly informative. The authors briefly review the neuroanatomy of gait, review
      gait abnormalities seen in psychiatric and neurologic disorders, and describe the
      assessment of gait.

PMID- 20805919
TI  - Mental healthcare utilization and sleep disturbance: a pilot study.
AB  - Disturbances in sleep are empirically associated with a number of different
      psychiatric disorders. In this pilot study, we examined whether four general
      queries about mental healthcare utilization ("Have you ever been seen by a
      psychiatrist?," "Have you ever been hospitalized in a psychiatric hospital?,"
      "Have you ever been in counseling?," and "Have you ever been on medication for
      your nerves?") would evidence correlations with various aspects of sleep
      disturbance as measured by the Pittsburgh Sleep Quality Index. In a cross
      sectional sample of convenience, we surveyed 75 internal medicine outpatients. We
      asked participants about the four preceding mental healthcare variables as well
      as sleep experiences using the Pittsburgh Sleep Quality Index. Prior to
      statistical analyses, we assigned one point to each mental healthcare utilization
      variable endorsed and developed a composite score (0-4). In analyses, while the
      mental-healthcare-utilization composite score was not related to overall sleep
      quality (i.e., the Global Pittsburgh Sleep Quality Index Score), it was
      statistically significantly related to the Pittsburgh Sleep Quality Index
      component of Sleep Disturbance (p<.01). This suggests that while individuals with
      greater mental healthcare utilization do not evidence differences in overall
      sleep quality compared to those with low utilization, they do report more
      disturbances in sleep.

PMID- 20805920
TI  - Sufism, Hazrat Inayat Khan, and his music.

PMID- 20805921
TI  - Cognitive impairments in major depression and bipolar disorders.

PMID- 20805923
TI  - Regarding the art of psychodynamic psychotherapy.

PMID- 20805922
TI  - Prescribing for buprenorphine in the treatment of opioid addiction.

PMID- 20805924
TI  - Risperidone-induced enuresis in an adult.

PMID- 20805925
TI  - The Reliability of Psychiatric Diagnoses: Point-Our psychiatric Diagnoses are
      Still Unreliable.

PMID- 20805926
TI  - Managing depressive disorders in patients with epilepsy.
AB  - Patients with epilepsy are more likely to suffer from psychiatric illnesses, and
      more specifically depressive disorders (9% to 22%), than the general population.
      Depression in epilepsy is often described by the temporal correlation to a
      seizure, with interictal depression being the most commonly described.
      Furthermore, epileptic patients with depression often report a poorer quality of
      life on global assessments and are at an increased risk of suicide as compared to
      the general population, 11.5 percent versus 1.2 percent, respectively. Despite
      the clinical significance of depression, it often goes unrecognized and hence
      untreated in this population. Recently, more efforts at screening epilepsy
      patients for coexisting depression have been undertaken, yielding fair results.
      However, some epilepsy patients express a certain constellation of symptoms,
      including an explosive or irritable mood, somatic pains, anxiety and fear, and
      periods of brief euphoria, which are not captured by common depression screening
      tools. Fears of antidepressants lowering seizure thresholds coupled with
      potential pharmacokinetic interactions between antiepileptic and antidepressant
      medications have strongly contributed to the undertreatment of this population.
      Finally, the treatment of depressive disorders in epilepsy is understudied and
      the few existing research studies have yet to display an effective treatment.
      Depressive disorders in patients with epilepsy pose significant and specific
      problems with regard to recognition, diagnosis, and treatment that require
      careful and thorough management.

PMID- 20805927
TI  - Why Psychiatrists are Reluctant to Diagnose: Borderline Personality Disorder.
AB  - Clinicians can be reluctant to make a diagnosis of borderline personality
      disorder (BPD). One reason is that BPD is a complex syndrome with symptoms that
      overlap many Axis I disorders. This paper will examine interfaces between BPD and
      depression, between BPD and bipolar disorder, and between BPD and psychoses. It
      will suggest that making a BPD diagnosis does more justice to patients than
      avoiding it.

PMID- 20805928
TI  - More than Medication-Achieving Goals through Psychotherapy in Patients with
      Obsessive Compulsive Disorder.
AB  - There are numerous variables to consider when planning treatment for a
      psychiatric disorder as complex as obsessive compulive disorder (OCD). Beyond the
      efficacy of the medications, one must take into account patient preferences and
      beliefs, as well as the impact of the disease and treatment on social and
      occupational functioning. Psychotherapy, specifically cognitive behavioral
      therapy (CBT), can serve as an addition to pharmacotherapy or as an alternative
      treatment, if necessary, for OCD. However, psychotherapy remains under-utilized.
      In this article, the authors review the available evidence supporting various
      treatment options for OCD and describe how psychotherapy (specifically CBT) can
      be used as monotherapy for OCD or as an adjunct to medication. Effective
      strategies for delivering CBT via its two modalities (exposure-response
      prevention and cognitive therapy) are described and illustrated by a composite
      case.

PMID- 20805929
TI  - A description of the use of music therapy in consultation-liaison psychiatry.
AB  - Music therapy is gaining increasing recognition for its benefit in medical
      settings both for its salutary effects on physiological parameters and on
      psychological states associated with medical illness. This article discusses the
      role of a music therapist in consultation-liaison psychiatry, a specialty that
      provides intervention for medical and surgical patients with concomitant mental
      health issues.We describe the ways in which music therapy has been integrated
      into the consultation-liaison psychiatry service at Hahnemann University
      Hospital, a tertiary care facility and major trauma center in Philadelphia. The
      referral process and some of the techniques used in music therapy are explained.
      Anecdotal observations illustrate how a music therapist incorporates the various
      elements of music as well as the experiences of engaging in music-making to bring
      about changes in mood and facilitate expression of feelings and social
      interactions in patients who are having difficulty coping with the effects of
      illness and hospitalization. These methods have also been observed to have
      positive effects on the hospital staff by making available a means with which
      staff can express pressures inherent in direct patient care.

PMID- 20805930
TI  - A model for improving microbial biofuel production using a synthetic feedback
      loop.
AB  - Cells use feedback to implement a diverse range of regulatory functions. Building
      synthetic feedback control systems may yield insight into the roles that feedback
      can play in regulation since it can be introduced independently of native
      regulation, and alternative control architectures can be compared. We propose a
      model for microbial biofuel production where a synthetic control system is used
      to increase cell viability and biofuel yields. Although microbes can be
      engineered to produce biofuels, the fuels are often toxic to cell growth,
      creating a negative feedback loop that limits biofuel production. These toxic
      effects may be mitigated by expressing efflux pumps that export biofuel from the
      cell. We developed a model for cell growth and biofuel production and used it to
      compare several genetic control strategies for their ability to improve biofuel
      yields. We show that controlling efflux pump expression directly with a biofuel
      responsive promoter is a straightforward way of improving biofuel production. In
      addition, a feed forward loop controller is shown to be versatile at dealing with
      uncertainty in biofuel production rates.

PMID- 20805931
TI  - Phenotypic impact of regulatory noise in cellular stress-response pathways.
AB  - Recent studies indicate that intrinsic promoter-mediated gene expression noise
      can confer a selective advantage under acute environmental stress by providing
      beneficial phenotypic diversity within cell populations. To investigate how
      extrinsic gene expression noise impacts the fitness of cell populations under
      stress, we engineered two nearly isogenic budding yeast strains; one carrying a
      two-step regulatory cascade that allows for precise control of the noise
      transmitted from a transcriptional regulator to a downstream stress-inducing
      gene, and one carrying a network with low constant upstream noise. The fitness
      and gene expression of these strains were compared under acute and prolonged
      stress exposure. Using a phenomenological modeling approach, we predicted that
      increased noise should confer a fitness advantage under high stress conditions,
      but reciprocally reduce the resistance of the population to low stress. The model
      also predicted that extrinsic noise might serve as a basis for phenotypic
      plasticity whereby gene expression distributions are modulated in response to
      prolonged stress. Experimentally, we confirmed the predicted differential fitness
      advantage of extrinsic noise under acute stress, as well as the predicted
      modulation of gene expression under prolonged stress. However, contrary to model
      predictions, strains with low and high extrinsic noise showed very similar
      adaptive responses to prolonged stress. This suggests that while phenotypic
      heterogeneity generated by noise in regulatory signals can confer increased
      robustness to acute stress, it is not a requirement for the observed long-term
      phenotypic plasticity.

PMID- 20805932
TI  - A synthetic biology approach allows inducible retrotransposition in whole plants.
AB  - Retrotransposons are mobile genetic elements that transpose by reverse
      transcription of element RNA, followed by insertion of the cDNA into new
      positions of the host genome. Although they are major constituents of eukaryotic
      genomes, many facets of their biology remain to be understood. Transposition is
      generally rare, suggesting that it is subject to tight regulation. However, only
      the first regulatory step (transcriptional induction) is currently amenable to
      investigation in higher eukaryotes. To investigate the complete life cycle of a
      long terminal repeat (LTR) retrotransposon in plants, we established a synthetic
      biology program on tobacco retrotransposon Tto1, and achieved transposition in
      whole plants triggered by an inducible promoter. The engineered element, iTto
      (inducible Tto1), is a novel tool for analysis of retrotransposition in plants.
      In addition, it allows to explore the potential of an inducible retrotransposon
      for insertional mutagenesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online
      version of this article (doi:10.1007/s11693-010-9053-4) contains supplementary
      material, which is available to authorized users.

PMID- 20805933
TI  - Towards a matrix mechanics framework for dynamic protein network.
AB  - Protein-protein interaction networks are currently visualized by software
      generated interaction webs based upon static experimental data. Current state is
      limited to static, mostly non-compartmental network and non time resolved protein
      interactions. A satisfactory mathematical foundation for particle interactions
      within a viscous liquid state (situation within the cytoplasm) does not exist nor
      do current computer programs enable building dynamic interaction networks for
      time resolved interactions. Building mathematical foundation for intracellular
      protein interactions can be achieved in two increments (a) trigger and capture
      the dynamic molecular changes for a select subset of proteins using several model
      systems and high throughput time resolved proteomics and, (b) use this
      information to build the mathematical foundation and computational algorithm for
      a compartmentalized and dynamic protein interaction network. Such a foundation is
      expected to provide benefit in at least two spheres: (a) understanding physiology
      enabling explanation of phenomenon such as incomplete penetrance in genetic
      disorders and (b) enabling several fold increase in biopharmaceutical production
      using impure starting materials.

PMID- 20805934
TI  - Stoma-Closure-Induced Fulminant Pseudomembranous Colitis Recovered by Adjunctive
      Intracolic Vancomycin with Postural Change.
AB  - A 67-year-old man with a history of low anterior resection and diverting loop
      transverse colostomy for rectal carcinoma developed fulminant pseudomembranous
      colitis after stoma closure. Oral administration of vancomycin at 0.5 g every 6 h
      and colonoscopy with intracolic vancomycin administration was unsuccessful, but
      continuation of intracolic vancomycin with postural change resulted in dramatic
      recovery. Postural change may extend the efficacy of intracolic vancomycin, and
      intracolic vancomycin should be considered as an option between conventional
      therapy and surgical intervention for pseudomembranous colitis.

PMID- 20805935
TI  - Ectopic Hepatocellular Carcinoma Arising in the Left Triangular Ligament of the
      Liver.
AB  - Hepatocellular carcinoma (HCC) rarely originates in extrahepatic liver tissue.
      Laparoscopic resection is widely used to treat HCC. This report presents a case
      of a patient with ectopic HCC arising in the left triangular ligament of the
      liver that was successfully treated by laparoscopic resection. A 59-year-old
      female presented with an elevated serum alpha-fetoprotein (AFP) level (2,508
      ng/ml). Dynamic computed tomography demonstrated a tumor measuring 20 mm in
      diameter below the left diaphragm just adjacent to the spleen. The tumor showed
      contrast enhancement in the hepatic arterial phase and became less dense than the
      liver parenchyma in the portal phase. The patient was diagnosed with ectopic HCC
      arising in the left diaphragm and laparoscopic surgery was performed. The tumor
      was located in the left triangular ligament of the liver and had a stalk between
      the tumor and the liver. The tumor was resected, and the final diagnosis was
      moderately differentiated ectopic HCC arising in the left triangular ligament of
      the liver. The patient had an uneventful postoperative recovery and has
      experienced no recurrence over 18 months after the operation.

PMID- 20805936
TI  - Immunohistochemical Examination of a Resected Advanced Hilar Cholangiocarcinoma
      Arising in a 29-Year-Old Male without Primary Sclerosing Cholangitis.
AB  - A 29-year-old man with advanced hilar cholangiocarcinoma was successfully treated
      with an extended right lobectomy. The carbohydrate antigen 19-9 (CA19-9) level
      was elevated to 939 IU/l, and the pathological findings revealed moderately
      differentiated tubular adenocarcinoma which involved almost the entire thickness
      of the hepatic duct and the adjacent liver tissue (T3) and which was associated
      with lymph node metastasis (N1). It was a stage IIB (T3N1M0) tubular
      adenocarcinoma according to UICC pathological staging. Immunohistochemical
      examination revealed that Ki-67, cyclin D1, and MMP-7 were positive, and 14-3
      3sigma and p27 were negative. The pathological and immunohistochemical findings
      indicated high malignant potential indicating poor prognosis. We administrated
      the postoperative adjunct gemcitabine combined with S-1 chemotherapy. The patient
      is alive without recurrence and doing well two years after surgery. We also
      review other reports of cholangiocarcinoma patients aged less than 30 years.

PMID- 20805937
TI  - Therapy Adherence in Crohn's Disease: An Adult Case Study.
AB  - Patients with Crohn's disease require long-term therapy and physician follow-up
      to treat symptoms, minimize complications of the disease, and address side
      effects that may occur due to therapeutic interventions. Once stabilized, it is
      not unusual for patients to question the need for continued therapy. This may be
      related to various factors including poor disease awareness, lack of adequate
      communication between the physician and the patient, not wanting to take
      medications chronically, and/or financial issues among a host of other
      possibilities. However, nonadherence can have a serious impact on morbidity and
      mortality in patients with Crohn's disease. This case illustrates the management
      and stabilization of a patient with active Crohn's disease and the use of
      diagnostic serological testing to aid in disease risk assessment and treatment
      guidance.

PMID- 20805938
TI  - Successful Treatment of Biliary Atresia in Very Small Infants through Living
      Related Liver Transplantation.
AB  - Improving outcomes in very small children is a major goal of pediatric liver
      transplantation. This report describes our experience of living related liver
      transplantation in an infant weighing 3.98 kg. The recipient, a 80-day-old male
      infant with congenital biliary atresia, was treated with living donor liver
      transplantation and then followed up for 6 months. The left lateral segment
      (segment II, III) with reduced size from the donor, his 26-year-old mother, was
      used as the graft. The graft weighed 200 g. The graft weight to recipient body
      weight ratio was 5.025%. The donor regained her liver function within 3 days and
      was discharged on day 8. The patient showed good results. Liver function returned
      to normal 9 days after the operation with bilirubin level almost decreased to
      normal. Cyclosporin, mycophenolate mofetil and prednisone were used for
      postoperative immunosuppression. No bleeding, thrombosis, infection or bile
      leakage occurred. The patient had slight fever because of a little collection in
      the abdomen and recovered after paracentesis and drainage. He was discharged on
      day 16. The donor and recipient are in satisfactory condition at present.
      Improvement of technique in hepatic surgery, microsurgical technique in vascular
      surgery and postoperative intensive care are the keys to ensure the success of
      the procedure.

PMID- 20805939
TI  - The Face of Tropical Sprue in 2010.
AB  - Tropical sprue (TS), although endemic in certain tropical regions of the world,
      is rarely seen in North America and Europe. However, in this era of globalization
      and worldwide travel, it is important for all clinicians to be aware of the
      possibility of TS in patients presenting with nonspecific, persistent
      gastrointestinal complaints like diarrhea and weight loss. The symptoms and
      histologic findings of TS can resemble and be confused with those of diseases
      seen more commonly in nontropical climates like celiac disease and small
      intestine bacterial overgrowth. Therefore, if the usual causes of persistent
      diarrhea are ruled out, keeping a high index of suspicion for TS in patients who
      have a travel history to one of the endemic regions is important.

PMID- 20805940
TI  - Current Diagnosis and Management of Gastrojejunocolic Fistula.
AB  - We herein report the case of a 51-year-old man with gastrojejunocolic fistula. It
      is one of the late severe complications of gastrectomy and gastrojejunostomy and
      is considered to be induced by a stomal ulcer due to inadequate resection of the
      stomach and incompleteness of vagotomy. The main clinical presentation of this
      condition is chronic abdominal pain, weight loss, diarrhea, gastrointestinal
      bleeding and fecal vomiting. The diagnostic workup should include barium enema,
      gastroscopy and sometimes colonoscopy and abdominal tomography for excluding and
      ruling out the possibility of malignant extraluminal disease. The historical
      approach of the treatment of this rare entity was 2-3-phased operations which
      included colostomy. However today, medical management has recently been
      recommended as the first-line therapy, with parenteral and enteral support
      treatments. The preferred surgical approach is single-stage gastrocolic resection
      and anastomosis and this has been favored to minimize mortality.

PMID- 20805941
TI  - A Case of Neuroendocrine Cell Carcinoma with Sigmoidovesical Fistula.
AB  - Colonic neuroendocrine cell carcinoma (NEC), which is a rare subtype of colon
      epithelial neoplasm, has been reported to show extremely aggressive
      characteristics with a 1-year survival rate of 20%. We report herein a resected
      case of NEC that manifested bacterial sepsis due to sigmoidovesical fistula.
      Staged surgery consisted of resecting the sigmoid colon and part of the bladder
      four weeks after construction of an ileostomy to alleviate septic shock. The
      resected specimen was histologically diagnosed as NEC invading the wall of the
      urinary bladder with metastasis to the regional lymph nodes. The patient
      underwent four cycles of FOLFOX after surgery for additional treatment of
      residual metastatic lymph nodes around the abdominal aorta diagnosed
      preoperatively. Although the patient showed stable disease measured by computed
      tomography scan for the first three months after surgery, he rejected additional
      chemotherapy thereafter, and died ten months after the initial admission due to
      progression of residual tumor in the urinary bladder as well as the lymph nodes.
      This is the first case report describing colonic NEC manifesting perforation into
      the urinary bladder. Although the optimal chemotherapeutic regimen for colonic
      NEC has not yet been established, FOLFOX may be one of the choices.

PMID- 20805942
TI  - Gastric Outlet Obstruction Palliation: A Novel Stent-Based Solution.
AB  - Gastric outlet obstruction (GOO) after esophagectomy is a morbid outcome and
      significantly hinders quality of life for end-stage esophageal cancer patients.
      In the pre-stent era, palliation consisted of chemotherapy, radiation, tumor
      ablation, or stricture dilation. In the current era, palliative stenting has
      emerged as an additional tool; however, migration and tumor ingrowth are ongoing
      challenges. To mitigate these challenges, we developed a novel, hybrid, stent
      based approach for the palliative management of GOO. We present a patient with
      esophageal cancer diagnosed with recurrent, metastatic disease 1 year after
      esophagectomy. She developed dehydration and intractable emesis, which
      significantly interfered with her quality of life. For palliation, we dilated the
      stenosis and proceeded with our stent-based solution. Using a combined endoscopic
      and fluoroscopic approach, we placed a 12-mm silicone salivary bypass tube across
      the pylorus, where it kinked slightly because of local tumor biology. To bridge
      this defect and ensure luminal patency, we placed a nitinol tracheobronchial
      stent through the silicone stent. Clinically, the patient had immediate relief
      from her pre-operative symptoms and was discharged home on a liquid diet. In
      conclusion, GOO and malignant dysphagia after esophagectomy are significant
      challenges for patients with end-stage disease. Palliative stenting is a viable
      option, but migration and tumor ingrowth are common complications. The hybrid
      approach presented here provides a unique solution to these potential pitfalls.
      The flared silicone tube minimized the chance of migration and impaired tumor
      ingrowth. The nitinol stent aided with patency and overcame the challenges of the
      soft tube. This novel strategy achieved palliation, describing another endoscopic
      option in the treatment of malignant GOO.

PMID- 20805943
TI  - Spontaneously Ruptured Giant Splenic Cyst with Elevated Serum Levels of CA 19-9,
      CA 125 and Carcinoembryonic Antigen.
AB  - Splenic cyst is a relatively rare disease; however, the occurrence of
      complications associated with its rupture is even more rare. A 20-year-old female
      patient who had severe abdominal and left shoulder pain was admitted to our
      hospital. The patient's abdomen was hard and tender to the touch and she
      presented with a high fever. The patient's serum levels of the tumor markers
      carbohydrate antigen 19-9, cancer antigen 125 and carcinoembryonic antigen were
      high. Ultrasonography and computed tomography of the abdomen showed an 11-cm
      multilocular cystic lesion in the spleen and the presence of free intraperitoneal
      fluid. Peritonitis with ruptured splenic cyst was diagnosed, and the patient
      underwent an emergency laparotomy. The abdominal cavity was filled with purulent
      fluid. The cyst was localized to the spleen and had already ruptured. Total
      splenectomy and cyst resection were performed. The postoperative course was
      uneventful. The patient was discharged on day 9 following surgery. The
      histological findings showed the lesion to be a benign epidermoid cyst completely
      lined with inner stratified squamous epithelium with a capsule of connective
      tissue. In the immunostaining analyses, the squamous epithelium was positive for
      carcinoembryonic antigen. A ruptured splenic cyst causes sudden onset of severe
      peritonitis and elevation of serous tumor markers. An emergency operation is
      indicated as the treatment for a ruptured splenic cyst with peritonitis, after
      which a favorable outcome can be expected.

PMID- 20805944
TI  - A Fatal Aortoesophageal Fistula Caused by Critical Combination of Double Aortic
      Arch and Nasogastric Tube Insertion for Superior Mesenteric Artery Syndrome.
AB  - Double aortic arch (DAA) is a rare vascular congenital abnormality. Since a
      vascular ring surrounds bronchus and esophagus, any oral or nasal intubation can
      physically cause fatal aortoesophageal fistula (AEF). We report herein the first
      case of association of DAA and superior mesenteric artery (SMA) syndrome and the
      second case of AEF caused by nasogastric intubation in an adult with DAA. A 19
      year-old woman visited our hospital for nausea and vomiting. She was diagnosed
      with SMA syndrome by computed tomography (CT). Nasogastric intubation relieved
      her symptoms in 4 days. Extramural compression with top ulceration was found in
      esophagogastroduodenoscopy on the 5th hospital day. She suddenly showed massive
      hematemesis on the 12th hospital day. AEF was found by CT. Soon, she died despite
      of intensive care. Retrospective interview disclosed the fact that DAA was
      pointed out in her childhood. We conclude that intubation must be avoided in DAA
      and a detailed clinical interview about DAA is mandatory to avoid AEF.

PMID- 20805945
TI  - Staple Line Polyposis and Cytomegalovirus Infection after Stapled
      Haemorrhoidectomy.
AB  - Early bleeding after stapled haemorrhoidectomy (SH) is not uncommon. Late and
      persistent bleeding occurring weeks or months after SH, however, is rare; it has
      only been described in more than 10% of cases. It is attributed to the
      development of inflammatory polyps at the staple line. Occurrence of rectal
      bleeding in the presence of palpable polypoid lesions at the stapled anastomotic
      line can cause diagnostic confusions, and it is not uncommon that such lesions
      are initially confused with rectal carcinoma. We report a case of a 38-year-old
      male who presented with persistent rectal bleeding some 6 months after SH
      performed in another hospital. Rectal and colonoscopic examinations revealed
      polypoid lesions at the anastomotic line. The biopsy failed to confirm
      malignancy, but identified cytomegalovirus (CMV) infection. The development of
      multiple inflammatory polypoid lesions in conjunction with CMV infection at the
      stapled anastomotic line has caused a diagnostic confusion, but - after exclusion
      of cancer - this complication was efficiently treated by CMV infection
      eradication combined with surgical excision of the remaining polyps due to
      persistence of bleeding. This case is reported to highlight late bleeding due to
      inflammatory polyps after SH and to increase the awareness of surgeons and
      gastroenterologists of this benign but somewhat common complication.

PMID- 20805946
TI  - Intrapancreatic Accessory Spleen Misdiagnosed as a Nonsecreting Endocrine Tumor:
      Case Report and Review of the Literature.
AB  - In a large series of nonselected autopsy investigations an accessory spleen was
      found in 10-30%. The second most common site is the pancreatic tail (17%). We
      report a case of intrapancreatic accessory spleen misdiagnosed as a nonsecreting
      neuroendocrine tumor of the pancreas. Nuclear scintigraphy may provide the
      definitive diagnosis of an intrapancreatic spleen and therefore prevent patients
      from unnecessary major surgery.

PMID- 20805947
TI  - Lap-Protector and Circular Stapler Are Useful in Cystogastrostomy for Large
      Pancreatic Pseudocyst with Severe Infection.
AB  - Lap-Protector, which is an abdominal wall sealing device, is usually used for
      wound protection from implantation of malignant cells or pyogenic fluid. A
      circular stapler is a common easy-to-use device for anastomosis of the digestive
      tract. We report the case of an infected pancreatic pseudocyst which was treated
      by surgical procedure using these useful devices. A 69-year-old man was followed
      up in our hospital after severe acute pancreatitis. He had undergone drainage
      surgeries twice for intractable pancreatic abscess followed by severe acute
      pancreatitis. He was admitted to our hospital complaining of loss of appetite,
      hiccups, and high fever. Computed tomography of the abdomen revealed an infected
      pancreatic pseudocyst which compressed the gastric wall. Internal drainage into
      the stomach was performed using Lap-Protector and circular stapler. The patient
      recovered uneventfully. Recently many endoscopic or laparoscopic procedures in
      cystogastrostomy are reported; however, a conventional open surgical approach is
      also important. This easy method may be useful for operative cystogastrostomy.

PMID- 20805948
TI  - Left Ventricular Thrombosis in Ulcerative Colitis.
AB  - Left ventricular thrombi usually occur in the setting of an acute myocardial
      infarction, left ventricular aneurysm, or dilated cardiomyopathy. In the absence
      of ventricular wall motion abnormalities, they are rare. This report describes a
      patient with ulcerative colitis in whom two-dimensional echocardiography revealed
      a left intraventricular mass. Thrombosis in ulcerative colitis is a serious
      condition and can occur in a very young population. This case also shows that
      left ventricular thrombi can occur in the active setting of ulcerative colitis.

PMID- 20805949
TI  - Rectovaginal Fistula after Low Anterior Resection for Rectal Cancer Using a
      Double Stapling Technique.
AB  - A 55-year-old female underwent low anterior resection for rectal cancer using a
      double stapling technique. She developed a rectovaginal fistula on the 9th
      postoperative day. She was discharged from hospital after undergoing transverse
      colostomy, and 5 months later she underwent transvaginal repair of the
      rectovaginal fistula. She subsequently had an uneventful recovery. The leading
      cause of this complication is involvement of the posterior wall of the vagina in
      the staple line when firing the circular stapler. Transvaginal repair with a
      diverting stoma for rectovaginal fistula is a safe, minimally invasive and
      effective method.

PMID- 20805950
TI  - Malignant Peritoneal Mesothelioma Mimicking Ischemic Colitis.
AB  - The prognosis of malignant peritoneal mesothelioma is extremely poor with a mean
      survival time of 12 months. The initial symptoms are poor and atypical. Because
      of its rare entity and little knowledge of its treatments, there are few reports
      of long-term survival. We encountered a very unique case with strong impression
      on radiological findings of malignant peritoneal methothelioma. We had
      misdiagnosed it because of the findings and because the time course was similar
      to that of ischemic colitis. The radiological findings on CT and enema
      disappeared within one week after antibiotic therapy.

PMID- 20805951
TI  - Primary Submucosal Squamous Cell Carcinoma of the Rectum Diagnosed by Endoscopic
      Ultrasound: Case Report and Literature Review.
AB  - Primary colorectal squamous cell carcinoma (SCC) is one of the very rare
      malignancies of the gastrointestinal tract. The diagnosis cannot be made before
      ruling out other common primary sites. Using the endoscopic ultrasound (EUS)
      technique to get a tissue biopsy for submucosal tumors has not been demonstrated
      as the best diagnostic approach in the literature. Surgery is the gold standard
      treatment with arising evidence of good efficacy following conventional
      chemoradiation therapy. A 49-year-old male presented with rectal discomfort.
      Sigmoidoscopy revealed multiple submucosal masses in the rectosigmoid colon.
      Mucosal biopsies showed nonspecific inflammation. Subsequently, an EUS with fine
      needle biopsy was done and established the diagnosis of rectal SCC. There were no
      other primary sites noticed in the extensive evaluation. The patient chose to be
      treated only with chemoradiation without surgery. At the time of writing this
      report he had no evidence of recurrence achieving 2.5 years of survival. EUS is
      an emerging excellent approach to diagnose submucosal colorectal SCC. This case
      will add supportive evidence of having a complete response following combining
      treatment with squamous cell directed chemotherapy and external beam radiotherapy
      without preceded surgery.

PMID- 20805952
TI  - Gastrointestinal Stromal Tumors with Unusual Localization: Report of Three Cases
      with a Brief Literature Review.
AB  - The most common tumors derived from the mesenchyme of the gastrointestinal system
      are stromal tumors. These tumors are typically seen in the stomach and small
      intestine and less frequently in the colon, rectum and esophagus and are very
      rarely located outside the gastrointestinal system. Cure is provided with
      complete surgical resection with resection borders free of tumor. Tumor size,
      mitotic index, localization, CD117 and CD34 negativity in immunohistochemical
      studies, mucosal ulceration and presence of necrosis help to predict recurrence
      of the illness and patient survival. In high-risk gastrointestinal stromal tumors
      (GISTs) there is an increased rate of recurrence and shortened survival despite
      complete surgical resection. Thus patients with a high-risk GIST should be given
      adjuvant therapy with imatinib mesylate. Sunitinib maleate is another FDA
      approved agent only for cases who cannot tolerate imatinib or who are resistant
      to it. Herein we present three cases with GISTs in different locations of the
      gastrointestinal system with a review of the relevant literature.

PMID- 20805953
TI  - Very-Low-Dose Pegylated Interferon a2a Plus Ribavirin Therapy for Advanced Liver
      Cirrhosis Type C: A Possible Therapeutic Alternative without Splenic
      Intervention.
AB  - Despite the recent progress in interferon (IFN) therapies for chronic hepatitis
      C, liver cirrhosis remains refractory. One of the major obstacles to successful
      IFN therapy is low platelet count. Currently, splenic interventions, such as
      partial splenic embolization (PSE) or surgical splenectomy, have been applied
      effectively and make standard IFN therapy possible. However, there may be a group
      of patients with low platelet counts who can be treated without splenic
      intervention. We here report two patients with advanced type C liver cirrhosis
      who were successfully treated using very-low-dose pegylated interferon a2a plus
      ribavirin. One patient had a very low platelet count (2.5 x 10(4)/mul) due to
      splenomegaly before treatment. However, pretreatment serum HCV titers were low in
      both patients and early viral responses were obtained in both. Because PSE or
      splenectomy may still have some safety concerns, this attenuated IFN treatment
      protocol can be an alternative therapeutic option for patients with advanced type
      C liver disease, but good virological factors for sustained virological response.

PMID- 20805954
TI  - The tissue microarray OWL schema: An open-source tool for sharing tissue
      microarray data.
AB  - BACKGROUND: Tissue microarrays (TMAs) are enormously useful tools for
      translational research, but incompatibilities in database systems between various
      researchers and institutions prevent the efficient sharing of data that could
      help realize their full potential. Resource Description Framework (RDF) provides
      a flexible method to represent knowledge in triples, which take the form Subject
      Predicate-Object. All data resources are described using Uniform Resource
      Identifiers (URIs), which are global in scope. We present an OWL (Web Ontology
      Language) schema that expands upon the TMA data exchange specification to address
      this issue and assist in data sharing and integration. METHODS: A minimal OWL
      schema was designed containing only concepts specific to TMA experiments. More
      general data elements were incorporated from predefined ontologies such as the
      NCI thesaurus. URIs were assigned using the Linked Data format. RESULTS: We
      present examples of files utilizing the schema and conversion of XML data
      (similar to the TMA DES) to OWL. CONCLUSION: By utilizing predefined ontologies
      and global unique identifiers, this OWL schema provides a solution to the
      limitations of XML, which represents concepts defined in a localized setting.
      This will help increase the utilization of tissue resources, facilitating
      collaborative translational research efforts.

PMID- 20805956
TI  - Whole slide imaging for teleconsultation and clinical use.

PMID- 20805955
TI  - Development of electronic medical record charting for hospital-based transfusion
      and apheresis medicine services: Early adoption perspectives.
AB  - BACKGROUND: Electronic medical records (EMRs) provide universal access to health
      care information across multidisciplinary lines. In pathology departments,
      transfusion and apheresis medicine services (TAMS) involved in direct patient
      care activities produce data and documentation that typically do not enter the
      EMR. Taking advantage of our institution's initiative for implementation of a
      paperless medical record, our TAMS division set out to develop an electronic
      charting (e-charting) strategy within the EMR. METHODS: A focus group of our
      hospital's transfusion committee consisting of transfusion medicine specialists,
      pathologists, residents, nurses, hemapheresis specialists, and information
      technologists was constituted and charged with the project. The group met
      periodically to implement e-charting TAMS workflow and produced electronic
      documents within the EMR (Cerner Millenium) for various service line functions.
      RESULTS: The interdisciplinary working group developed and implemented electronic
      versions of various paper-based clinical documentation used by these services.
      All electronic notes collectively gather and reside within a unique Transfusion
      Medicine Folder tab in the EMR, available to staff with access to patient charts.
      E-charting eliminated illegible handwritten notes, resulted in more consistent
      clinical documentation among staff, and provided greater realered. However, minor
      updates and corrections to documents as well as select work re-designs were
      required for optimal use of e-charting-time review/access of hemotherapy
      practices. No major impediments to workflow or inefficiencies have been encount
      by these services. CONCLUSION: Documentation of pathology subspecialty activities
      such as TAMS can be successfully incorporated into the EMR. E-charting by staff
      enhances communication and helps promote standardized documentation of patient
      care within and across service lines. Well-constructed electronic documents in
      the EMR may also enhance data mining, quality improvement, and biovigilance
      monitoring activities.

PMID- 20805957
TI  - HIMSS10 - Perspectives from a newcomer pathologist and a seasoned attendee
      pathologist: Pathologists should attend!

PMID- 20805958
TI  - Stepwise approach to establishing multiple outreach laboratory information system
      electronic medical record interfaces.
AB  - Clinical laboratory outreach business is changing as more physician practices
      adopt an electronic medical record (EMR). Physician connectivity with the
      laboratory information system (LIS) is consequently becoming more important.
      However, there are no reports available to assist the informatician with
      establishing and maintaining outreach LIS-EMR connectivity. A four-stage scheme
      is presented that was successfully employed to establish unidirectional and
      bidirectional interfaces with multiple physician EMRs. This approach involves
      planning (step 1), followed by interface building (step 2) with subsequent
      testing (step 3), and finally ongoing maintenance (step 4). The role of organized
      project management, software as a service (SAAS), and alternate solutions for
      outreach connectivity are discussed.

PMID- 20805959
TI  - Cytologic evaluation of image-guided fine needle aspiration biopsies via robotic
      microscopy: A validation study.
AB  - BACKGROUND: This study carried out was to assess the feasibility of using robotic
      microscopy (RM) for cytologic evaluation of direct smears from fine needle
      aspiration biopsy (FNAB). METHODS: Three board-certified cytopathologists
      reviewed representative direct smears from 40 image-guided FNABs using RM and
      subsequently re-reviewed the same smears using conventional microscopy. Adequacy
      of the smears and cytologic diagnosis, as determined using the two approaches,
      were compared for each individual cytopathologist (intraobserver) and between the
      three cytopathologists (interobserver). The intraobserver and interobserver
      discrepancies were analyzed and discussed in a follow-up consensus conference.
      RESULTS: FOR ASSESSMENT OF ADEQUACY, THERE WERE HIGH CONCORDANCE RATES
      (INTRAOBSERVER: 92.5-97.5%; interobserver: 90-92.5%), with a few discrepancies
      involving distinctions between suboptimal and satisfactory smears. Analysis of
      diagnostic interpretations showed correct classification of 92.5-95%
      (intraobserver) or 90-92.5% (interobserver) of benign and malignant cases
      combined, with the discrepancies being between benign and atypical cells in the
      benign group, and between suspicious and malignant in the malignant group. Within
      the malignant group, 94% of cases were accurately subclassified via RM. The
      quality of images viewed by using RM was rated adequate (fair or good) for 95% of
      the slides. CONCLUSIONS: The results demonstrate that cytologic evaluation of
      direct smears from FNABs using RM is feasible. Problems encountered included the
      longer times needed to evaluate cases with thick, bloody smears and/or low
      numbers of diagnostic cells, and difficulties in recognizing neuroendocrine
      differentiation and mimics of hepatocellular carcinoma.

PMID- 20805960
TI  - Overview of laboratory data tools available in a single electronic medical
      record.
AB  - BACKGROUND: Laboratory data account for the bulk of data stored in any given
      electronic medical record (EMR). To best serve the user, electronic laboratory
      data needs to be flexible and customizable. Our aim was to determine the various
      ways in which laboratory data get utilized by clinicians in our health system's
      EMR. METHOD: All electronic menus, tabs, flowsheets, notes and subsections within
      the EMR (Millennium v2007.13, Cerner Corporation, Kansas City, MO, US) were
      explored to determine how clinicians utilize discrete laboratory data. RESULTS:
      LABORATORY DATA IN THE EMR WERE UTILIZED BY CLINICIANS IN FIVE DISTINCT WAYS:
      within flowsheets, their personal inbox (EMR messaging), with decision support
      tools, in the health maintenance tool, and when incorporating laboratory data
      into their clinical notes and letters. CONCLUSIONS: Flexible electronic
      laboratory data in the EMR hava many advantages. Users can view, sort, pool, and
      appropriately route laboratory information to better support trend analyses,
      clinical decision making, and clinical charting. Laboratory data in the EMR can
      also be utilized to develop clinical decision support tools. Pathologists need to
      participate in the creation of these EMR tools in order to better support the
      appropriate utilization of laboratory information in the EMR.

PMID- 20805961
TI  - Development and use of a genitourinary pathology digital teaching set for trainee
      education.
AB  - BACKGROUND: Automated, high-speed, high-resolution whole slide imaging (WSI)
      robots are becoming increasingly robust and capable. This technology has started
      to have a significant impact on pathology practice in various aspects including
      resident education. To be sufficient and adequate, training in pathology requires
      gaining broad exposure to various diagnostic patterns through teaching sets,
      which are traditionally composed of glass slides. METHODS: A teaching set of over
      295 glass slides has been used for resident training at the Division of
      Genitourinary Pathology, Department of Pathology, University of Pittsburgh
      Medical Center. Whole slide images were prepared from these slides using an
      Aperio ScanScope CS scanner. These images and case-related information were
      uploaded on a web-based digital teaching model. RESULTS: THE WEB SITE IS
      AVAILABLE AT: https://www.secure.opi.upmc.edu/genitourinary/index.cfm. Once
      logged in, users can view the list of cases, or search cases with or without
      diagnoses shown. Each case can be accessed through an option button, where the
      clinical history, gross findings are initially shown. Whole slide images can be
      accessed through the links on the page, which allows users to make diagnoses on
      their own. More information including final diagnosis will display when the
      diagnosis-button is clicked. CONCLUSION: The web-based digital study set provides
      additional educational benefits to using glass slides. Residents or other users
      can remotely access whole slide images and related information at their
      convenience. Searching and sorting functions and self-testing mode allow a more
      targeted study. It would also prepare residents with competence to work with
      whole slide images. Further, the model can be expanded to include pre-rotation
      and post-rotation exams, and/or a virtual rotation system, which may potentially
      make standardization of pathology resident training possible in the future.

PMID- 20805962
TI  - Computerized provider order entry systems - Research imperatives and
      organizational challenges facing pathology services.
AB  - Information and communication technologies (ICT) are contributing to major
      changes taking place in pathology and within health services more generally. In
      this article, we draw on our research experience for over 7 years investigating
      the implementation and diffusion of computerized provider order entry (CPOE)
      systems to articulate some of the key informatics challenges confronting
      pathology laboratories. The implementation of these systems, with their improved
      information management and decision support structures, provides the potential
      for enhancing the role that pathology services play in patient care pathways.
      Beyond eliminating legibility problems, CPOE systems can also contribute to the
      efficiency and safety of healthcare, reducing the duplication of test orders and
      diminishing the risk of misidentification of patient samples and orders. However,
      despite the enthusiasm for CPOE systems, their diffusion across healthcare
      settings remains variable and is often beset by implementation problems.
      Information systems like CPOE may have the ability to integrate work, departments
      and organizations, but unfortunately, health professionals, departments and
      organizations do not always want to be integrated in ways that information
      systems allow. A persistent theme that emerges from the research evidence is that
      one size does not fit all, and system success or otherwise is reliant on the
      conditions and circumstances in which they are located. These conditions and
      circumstances are part of what is negotiated in the complex, messy and
      challenging area of ICT implementation. The solution is not likely to be simple
      and easy, but current evidence suggests that a combination of concerted efforts,
      better research designs, more sophisticated theories and hypotheses as well as
      more skilled, multidisciplinary research teams, tackling this area of study will
      bring substantial benefits, improving the effectiveness of pathology services,
      and, as a direct corollary, the quality of patient care.

PMID- 20805965
TI  - Why Another journal?

PMID- 20805964
TI  - Introducing the journal of pathology informatics.

PMID- 20805966
TI  - Twenty years of European hair research society.

PMID- 20805963
TI  - The pathology informatics curriculum wiki: Harnessing the power of user-generated
      content.
AB  - BACKGROUND: The need for informatics training as part of pathology training has
      never been so critical, but pathology informatics is a wide and complex field and
      very few programs currently have the resources to provide comprehensive
      educational pathology informatics experiences to their residents. In this
      article, we present the "pathology informatics curriculum wiki", an open, on-line
      wiki that indexes the pathology informatics content in a larger public wiki,
      Wikipedia, (and other online content) and organizes it into educational modules
      based on the 2003 standard curriculum approved by the Association for Pathology
      Informatics (API). METHODS AND RESULTS: In addition to implementing the
      curriculum wiki at http://pathinformatics.wikispaces.com, we have evaluated
      pathology informatics content in Wikipedia. Of the 199 non-duplicate terms in the
      API curriculum, 90% have at least one associated Wikipedia article. Furthermore,
      evaluation of articles on a five-point Likert scale showed high scores for
      comprehensiveness (4.05), quality (4.08), currency (4.18), and utility for the
      beginner (3.85) and advanced (3.93) learners. These results are compelling and
      support the thesis that Wikipedia articles can be used as the foundation for a
      basic curriculum in pathology informatics. CONCLUSIONS: The pathology informatics
      community now has the infrastructure needed to collaboratively and openly create,
      maintain and distribute the pathology informatics content worldwide (Wikipedia)
      and also the environment (the curriculum wiki) to draw upon its own resources to
      index and organize this content as a sustainable basic pathology informatics
      educational resource. The remaining challenges are numerous, but largest by far
      will be to convince the pathologists to take the time and effort required to
      build pathology informatics content in Wikipedia and to index and organize this
      content for education in the curriculum wiki.

PMID- 20805967
TI  - Journey through the world of hair.

PMID- 20805968
TI  - Some thoughts: scattered hair and there!

PMID- 20805970
TI  - Hair abnormalities in genetic disorders of junctions.
AB  - The desmosomes form the basis of intercellular support structure within the
      epidermis. However, various junctions, including gap junctions, adherens
      junctions, and tight junctions play an important part in the intercellular
      bridges that are vital for cell-cell interactions and structural stability.
      Numerous mutations can affect the genetic structure that make up these junctions
      and in turn cause disease. Most of these conditions have hair abnormalities and
      this article will briefly elucidate the various manifestations in the hair. As
      these junctional elements are found in other organs like the heart, liver, and
      eye, there could be serious systemic associations along with the hair changes.

PMID- 20805969
TI  - Oxidative stress in ageing of hair.
AB  - Experimental evidence supports the hypothesis that oxidative stress plays a major
      role in the ageing process. Reactive oxygen species are generated by a multitude
      of endogenous and environmental challenges. Reactive oxygen species or free
      radicals are highly reactive molecules that can directly damage cellular
      structural membranes, lipids, proteins, and DNA. The body possesses endogenous
      defence mechanisms, such as antioxidative enzymes and non-enzymatic antioxidative
      molecules, protecting it from free radicals by reducing and neutralizing them.
      With age, the production of free radicals increases, while the endogenous defence
      mechanisms decrease. This imbalance leads to the progressive damage of cellular
      structures, presumably resulting in the ageing phenotype. Ageing of hair
      manifests as decrease of melanocyte function or graying, and decrease in hair
      production or alopecia. There is circumstantial evidence that oxidative stress
      may be a pivotal mechanism contributing to hair graying and hair loss. New
      insights into the role and prevention of oxidative stress could open new
      strategies for intervention and reversal of the hair graying process and age
      dependent alopecia.

PMID- 20805971
TI  - Dealing wildlife offences in India: role of the hair as physical evidence.
AB  - India is known for its rich biodiversity, with a wide variety of wild floral and
      faunal species. This wildlife treasure of ours faces the threat of extinction due
      to rampant poaching and illegal trade. With most of the wildlife offence cases
      related to mammals having hair as physical evidence, it becomes imperative to use
      this evidence in the best possible way for wildlife crime investigation. We
      discuss the value of hair evidence with special reference to species
      characterization/identification using microscopic hair characteristics, keratin
      patterns, and mitochondrial DNA typing. The relevance of the techniques with
      respect to Indian scenario is specially taken care of and microscopic hair
      characteristics of one of the highly endangered species along with its keratin
      pattern are described. Finally, the use of mitochondrial DNA for species
      identification is also discussed.

PMID- 20805972
TI  - Finasteride induced Gynecomastia: Case report and Review of the Literature.
AB  - Finasteride (1 mg/day) is widely utilized by dermatologists for the treatment of
      androgenetic alopecia. Although enjoying a relatively good safety profile,
      several sex-related adverse effects have been reported with this drug. Here we
      report two cases of gynecomastia, one of them bilateral, caused by Propecia((R))
      prescribed for the treatment of androgenetic alopecia. Although relatively rare,
      physicians should be aware of this side effect and inform their patients when
      prescribing this medication.

PMID- 20805973
TI  - Neurodegenerative disorders with hair abnormalities: an emergency room
      consultation for dermatologists.
AB  - Menke's syndrome and Elejalde disease are the two neurodegenerative disorders of
      dermatological interest. These patients present with characteristic hair changes
      which may be of diagnostic value in resource-poor setup where facilities for
      specific genetic analysis are not available. Simple light microscopic examination
      of hair may be a helpful diagnostic tool to pick up such cases.

PMID- 20805974
TI  - Tonsuring: Myths and facts.

PMID- 20805975
TI  - Spangled hair in siblings.

PMID- 20805976
TI  - Parasite replication and the evolutionary epidemiology of parasite virulence.
AB  - Parasite virulence evolution is shaped by both within-host and population-level
      processes yet the link between these differing scales of infection is often
      neglected. Population structure and heterogeneity in both parasites and hosts
      will affect how hosts are exploited by pathogens and the intensity of infection.
      Here, it is shown how the degree of relatedness among parasites together with
      epidemiological parameters such as pathogen yield and longevity influence the
      evolution of virulence. Furthermore, the role of kin competition and the degree
      of cheating within highly structured parasite populations also influences
      parasite fitness and infectivity patterns. Understanding how the effects of
      within-host processes scale up to affect the epidemiology has importance for
      understanding host-pathogen interactions.

PMID- 20805977
TI  - An economic evaluation of home management of malaria in Uganda: an interactive
      Markov model.
AB  - BACKGROUND: Home management of malaria (HMM), promoting presumptive treatment of
      febrile children in the community, is advocated to improve prompt appropriate
      treatment of malaria in Africa. The cost-effectiveness of HMM is likely to vary
      widely in different settings and with the antimalarial drugs used. However, no
      data on the cost-effectiveness of HMM programmes are available. METHODS/PRINCIPAL
      FINDINGS: A Markov model was constructed to estimate the cost-effectiveness of
      HMM as compared to conventional care for febrile illnesses in children without
      HMM. The model was populated with data from Uganda, but is designed to be
      interactive, allowing the user to adjust certain parameters, including the
      antimalarials distributed. The model calculates the cost per disability adjusted
      life year averted and presents the incremental cost-effectiveness ratio compared
      to a threshold value. Model output is stratified by level of malaria transmission
      and the probability that a child would receive appropriate care from a health
      facility, to indicate the circumstances in which HMM is likely to be cost
      effective. The model output suggests that the cost-effectiveness of HMM varies
      with malaria transmission, the probability of appropriate care, and the drug
      distributed. Where transmission is high and the probability of appropriate care
      is limited, HMM is likely to be cost-effective from a provider perspective. Even
      with the most effective antimalarials, HMM remains an attractive intervention
      only in areas of high malaria transmission and in medium transmission areas with
      a lower probability of appropriate care. HMM is generally not cost-effective in
      low transmission areas, regardless of which antimalarial is distributed.
      Considering the analysis from the societal perspective decreases the
      attractiveness of HMM. CONCLUSION: Syndromic HMM for children with fever may be a
      useful strategy for higher transmission settings with limited health care and
      diagnosis, but is not appropriate for all settings. HMM may need to be tailored
      to specific settings, accounting for local malaria transmission intensity and
      availability of health services.

PMID- 20805978
TI  - Recent salmon declines: a result of lost feeding opportunities due to bad timing?
AB  - As the timing of spring productivity blooms in near-shore areas advances due to
      warming trends in global climate, the selection pressures on out-migrating salmon
      smolts are shifting. Species and stocks that leave natal streams earlier may be
      favoured over later-migrating fish. The low post-release survival of hatchery
      fish during recent years may be in part due to static release times that do not
      take the timing of plankton blooms into account. This study examined the effects
      of release time on the migratory behaviour and survival of wild and hatchery
      reared coho salmon (Oncorhynchus kisutch) using acoustic and coded-wire
      telemetry. Plankton monitoring and near-shore seining were also conducted to
      determine which habitat and food sources were favoured. Acoustic tags (n = 140)
      and coded-wire tags (n = 266,692) were implanted into coho salmon smolts at the
      Seymour and Quinsam Rivers, in British Columbia, Canada. Differences between wild
      and hatchery fish, and early and late releases were examined during the entire
      lifecycle. Physiological sampling was also carried out on 30 fish from each
      release group. The smolt-to-adult survival of coho salmon released during periods
      of high marine productivity was 1.5- to 3-fold greater than those released both
      before and after, and the fish's degree of smoltification affected their
      downstream migration time and duration of stay in the estuary. Therefore,
      hatchery managers should consider having smolts fully developed and ready for
      release during the peak of the near-shore plankton blooms. Monitoring chlorophyll
      a levels and water temperature early in the spring could provide a forecast of
      the timing of these blooms, giving hatcheries time to adjust their release
      schedule.

PMID- 20805979
TI  - Suppression of uPA and uPAR attenuates angiogenin mediated angiogenesis in
      endothelial and glioblastoma cell lines.
AB  - BACKGROUND: In our earlier reports, we showed that downregulation of uPA and uPAR
      inhibited glioma tumor angiogenesis in SNB19 cells, and intraperitoneal injection
      of a hairpin shRNA expressing plasmid targeting uPA and uPAR inhibited
      angiogenesis in nude mice. The exact mechanism by which inhibition of
      angiogenesis takes place is not clearly understood. METHODOLOGY/PRINCIPAL
      FINDINGS: In the present study, we have attempted to investigate the mechanism by
      which uPA/uPAR downregulation by shRNA inhibits angiogenesis in endothelial and
      glioblastoma cell lines. uPA/uPAR downregulation by shRNA in U87 MG and U87 SPARC
      co-cultures with endothelial cells inhibited angiogenesis as assessed by in vitro
      angiogenesis assay and in vivo dorsal skin-fold chamber model in nude mice.
      Protein antibody array analysis of co-cultures of U87 and U87 SPARC cells with
      endothelial cells treated with pU2 (shRNA against uPA and uPAR) showed decreased
      angiogenin secretion and angiopoietin-1 as well as several other pro-angiogenic
      molecules. Therefore, we investigated the role of angiogenin and found that
      nuclear translocation, ribonucleolytic and 45S rRNA synthesis, which are all
      critical for angiogenic function of angiogenin, were significantly inhibited in
      endothelial cells transfected with uPA, uPAR and uPA/uPAR when compared with
      controls. Moreover, uPA and uPAR downregulation significantly inhibited the
      phosphorylation of Tie-2 receptor and also down regulated FKHR activation in the
      nucleus of endothelial cells via the GRB2/AKT/BAD pathway. Treatment of
      endothelial cells with ruPA increased angiogenin secretion and angiogenin
      expression as determined by ELISA and western blotting in a dose-dependent
      manner. The amino terminal fragment of uPA down regulated ruPA-induced angiogenin
      in endothelial cells, thereby suggesting that uPA plays a critical role in
      positively regulating angiogenin in glioblastoma cells. CONCLUSIONS/SIGNIFICANCE:
      Taken together, our results suggest that uPA/uPAR downregulation suppresses
      angiogenesis in endothelial cells induced by glioblastoma cell lines partially by
      downregulation of angiogenin and by inhibition of the angiopoietin-1/AKT/FKHR
      pathway.

PMID- 20805980
TI  - Evolution of novel signal traits in the absence of female preferences in
      Neoconocephalus katydids (Orthoptera, Tettigoniidae).
AB  - BACKGROUND SIGNIFICANCE: Communication signals that function to bring together
      the sexes are important for maintaining reproductive isolation in many taxa.
      Changes in male calls are often attributed to sexual selection, in which female
      preferences initiate signal divergence. Natural selection can also influence
      signal traits if calls attract predators or parasitoids, or if calling is
      energetically costly. Neutral evolution is often neglected in the context of
      acoustic communication. METHODOLOGY/PRINCIPAL FINDINGS: We describe a signal
      trait that appears to have evolved in the absence of either sexual or natural
      selection. In the katydid genus Neoconocephalus, calls with a derived pattern in
      which pulses are grouped into pairs have evolved five times independently. We
      have previously shown that in three of these species, females require the double
      pulse pattern for call recognition, and hence the recognition system of the
      females is also in a derived state. Here we describe the remaining two species
      and find that although males produce the derived call pattern, females use the
      ancestral recognition mechanism in which no pulse pattern is required. Females
      respond equally well to the single and double pulse calls, indicating that the
      derived trait is selectively neutral in the context of mate recognition.
      CONCLUSIONS/SIGNIFICANCE: These results suggest that 1) neutral changes in signal
      traits could be important in the diversification of communication systems, and 2)
      males rather than females may be responsible for initiating signal divergence.

PMID- 20805981
TI  - Gut microbial gene expression in mother-fed and formula-fed piglets.
AB  - BACKGROUND: Effects of diet on the structure and function of gut microbial
      communities in newborn infants are poorly understood. High-resolution molecular
      studies are needed to definitively ascertain whether gut microbial communities
      are distinct in milk-fed and formula-fed infants. METHODOLOGY/PRINCIPAL FINDINGS:
      Pyrosequencing-based whole transcriptome shotgun sequencing (RNA-seq) was used to
      evaluate community wide gut microbial gene expression in 21 day old neonatal
      piglets fed either with sow's milk (mother fed, MF; n = 4) or with artificial
      formula (formula fed, FF; n = 4). Microbial DNA and RNA were harvested from cecal
      contents for each animal. cDNA libraries and 16S rDNA amplicons were sequenced on
      the Roche 454 GS-FLX Titanium system. Communities were similar at the level of
      phylum but were dissimilar at the level of genus; Prevotella was the dominant
      genus within MF samples and Bacteroides was most abundant within FF samples.
      Screened cDNA sequences were assigned functional annotations by the MG-RAST
      annotation pipeline and based upon best-BLASTX-hits to the NCBI COG database.
      Patterns of gene expression were very similar in MF and FF animals. All samples
      were enriched with transcripts encoding enzymes for carbohydrate and protein
      metabolism, as well as proteins involved in stress response, binding to host
      epithelium, and lipopolysaccharide metabolism. Carbohydrate utilization
      transcripts were generally similar in both groups. The abundance of enzymes
      involved in several pathways related to amino acid metabolism (e.g., arginine
      metabolism) and oxidative stress response differed in MF and FF animals.
      CONCLUSIONS/SIGNIFICANCE: Abundant transcripts identified in this study likely
      contribute to a core microbial metatranscriptome in the distal intestine.
      Although microbial community gene expression was generally similar in the cecal
      contents of MF and FF neonatal piglets, several differentially abundant gene
      clusters were identified. Further investigations of gut microbial gene expression
      will contribute to a better understanding of normal and abnormal enteric
      microbiology in animals and humans.

PMID- 20805983
TI  - Changing epidemiology of serious bacterial infections in febrile infants without
      localizing signs.
AB  - OBJECTIVE: Historically, management of infants with fever without localizing
      signs (FWLS) has generated much controversy, with attempts to risk stratify based
      on several criteria. Advances in medical practice may have altered the
      epidemiology of serious bacterial infections (SBIs) in this population. We
      conducted this study to test the hypothesis that the rate of SBIs in this patient
      population has changed over time. PATIENTS AND METHODS: We performed a
      retrospective review of all infants meeting FWLS criteria at our institution from
      1997-2006. We examined all clinical and outcome data and performed statistical
      analysis of SBI rates and ampicillin resistance rates. RESULTS: 668 infants met
      criteria for FWLS. The overall rate of SBIs was 10.8%, with a significant
      increase from 2002-2006 (52/361, 14.4%) compared to 1997-2001 (20/307, 6.5%) (p =
      0.001). This increase was driven by an increase in E. coli urinary tract
      infections (UTI), particularly in older infants (31-90 days). CONCLUSIONS: We
      observed a significant increase in E. coli UTI among FWLS infants with high rates
      of ampicillin resistance. The reasons are likely to be multifactorial, but the
      results themselves emphasize the need to examine urine in all febrile infants <90
      days and consider local resistance patterns when choosing empiric antibiotics.

PMID- 20805982
TI  - Tetrodotoxin-resistant sodium channels contribute to directional responses in
      starburst amacrine cells.
AB  - The biophysical mechanisms that give rise to direction selectivity in the retina
      remain uncertain. Current evidence suggests that the directional signal first
      arises within the dendrites of starburst amacrine cells (SBACs). Two models have
      been proposed to explain this phenomenon, one based on mutual inhibitory
      interactions between SBACs, and the other positing an intrinsic dendritic
      mechanism requiring a voltage-gradient depolarizing towards the dendritic tips.
      We tested these models by recording current and voltage responses to visual
      stimuli in SBACs. In agreement with previous work, we found that the excitatory
      currents in the SBACs were directional, and remained directional when GABA
      receptors were blocked. Contrary to the mutual-inhibitory model, stimuli that
      produce strong directional signals in ganglion cells failed to reveal a
      significant inhibitory input to SBACs. Suppression of the tonic excitatory
      conductance, proposed to generate the dendritic voltage-gradient required for the
      dendrite autonomous model, failed to eliminate the directional signal in SBACs.
      However, selective block of tetrodotoxin-resistant sodium channels did reduce the
      strength of the directional excitatory signal in the SBACs. These results
      indicate that current models of direction-selectivity in the SBACs are
      inadequate, and suggest that voltage-gated excitatory channels, specifically
      tetrodotoxin-resistant sodium channels, are important elements in directional
      signaling. This is the first physiological evidence that tetrodotoxin-resistant
      sodium channels play a role in retinal information processing.

PMID- 20805984
TI  - Ingestion of broccoli sprouts does not improve endothelial function in humans
      with hypertension.
AB  - Ingestion of glucosinolates has previously been reported to improve endothelial
      function in spontaneously hypertensive rats, possibly because of an increase in
      NO availability in the endothelium due to an attenuation of oxidative stress; in
      our study we tried to see if this also would be the case in humans suffering from
      essential hypertension. METHODS: 40 hypertensive individuals without diabetes and
      with normal levels of cholesterol were examined. The participants were randomized
      either to ingest 10 g dried broccoli sprouts, a natural donor of glucosinolates
      with high in vitro antioxidative potential, for a 4 week period or to continue
      their ordinary diet and act as controls. Blood pressure, endothelial function
      measured by flow mediated dilation (FMD) and blood samples were obtained from the
      participants every other week and the content of glucosinolates was measured
      before and after the study. Measurements were blinded to treatment allocation.
      RESULTS: In the interventional group overall FMD increased from 4% to 5.8% in the
      interventional group whereas in the control group FMD was stable (4% at baseline
      and 3.9% at the end of the study). The change in FMD in the interventional group
      was mainly due to a marked change in FMD in two participants while the other
      participants did not have marked changes in FMD. The observed differences were
      not statistically significant. Likewise significant changes in blood pressure or
      blood samples were not detected between or within groups. Diastolic blood
      pressure stayed essentially unchanged in both groups, while the systolic blood
      pressure showed a small non significant decrease (9 mm Hg) in the interventional
      group from a value of 153 mm Hg at start. CONCLUSION: Daily ingestion of 10 g
      dried broccoli sprouts does not improve endothelial function in the presence of
      hypertension in humans. TRIAL REGISTRATION: Clinicaltrials.gov NCT00252018.

PMID- 20805985
TI  - Ablation of Dicer from murine Schwann cells increases their proliferation while
      blocking myelination.
AB  - The myelin sheaths that surround the thick axons of the peripheral nervous system
      are produced by the highly specialized Schwann cells. Differentiation of Schwann
      cells and myelination occur in discrete steps. Each of these requires coordinated
      expression of specific proteins in a precise sequence, yet the regulatory
      mechanisms controlling protein expression during these events are incompletely
      understood. Here we report that Schwann cell-specific ablation of the enzyme
      Dicer1, which is required for the production of small non-coding regulatory
      microRNAs, fully arrests Schwann cell differentiation, resulting in early
      postnatal lethality. Dicer(-/-) Schwann cells had lost their ability to
      myelinate, yet were still capable of sorting axons. Both cell death and,
      paradoxically, proliferation of immature Schwann cells was markedly enhanced,
      suggesting that their terminal differentiation is triggered by growth-arresting
      regulatory microRNAs. Using microRNA microarrays, we identified 16 microRNAs that
      are upregulated upon myelination and whose expression is controlled by Dicer in
      Schwann cells. This set of microRNAs appears to drive Schwann cell
      differentiation and myelination of peripheral nerves, thereby fulfilling a
      crucial function for survival of the organism.

PMID- 20805986
TI  - Ecology and biogeography of free-living nematodes associated with chemosynthetic
      environments in the deep sea: a review.
AB  - BACKGROUND: Here, insight is provided into the present knowledge on free-living
      nematodes associated with chemosynthetic environments in the deep sea. It was
      investigated if the same trends of high standing stock, low diversity, and the
      dominance of a specialized fauna, as observed for macro-invertebrates, are also
      present in the nematodes in both vents and seeps. METHODOLOGY: This review is
      based on existing literature, in combination with integrated analysis of
      datasets, obtained through the Census of Marine Life program on Biogeography of
      Deep-Water Chemosynthetic Ecosystems (ChEss). FINDINGS: Nematodes are often
      thriving in the sulphidic sediments of deep cold seeps, with standing stock
      values ocassionaly exceeding largely the numbers at background sites. Vents seem
      not characterized by elevated densities. Both chemosynthetic driven ecosystems
      are showing low nematode diversity, and high dominance of single species. Genera
      richness seems inversely correlated to vent and seep fluid emissions, associated
      with distinct habitat types. Deep-sea cold seeps and hydrothermal vents are,
      however, highly dissimilar in terms of community composition and dominant taxa.
      There is no unique affinity of particular nematode taxa with seeps or vents.
      CONCLUSIONS: It seems that shallow water relatives, rather than typical deep-sea
      taxa, have successfully colonized the reduced sediments of seeps at large water
      depth. For vents, the taxonomic similarity with adjacent regular sediments is
      much higher, supporting rather the importance of local adaptation, than that of
      long distance distribution. Likely the ephemeral nature of vents, its long
      distance offshore and the absence of pelagic transport mechanisms, have prevented
      so far the establishment of a successful and typical vent nematode fauna. Some
      future perspectives in meiofauna research are provided in order to get a more
      integrated picture of vent and seep biological processes, including all
      components of the marine ecosystem.

PMID- 20805987
TI  - Genetic affinities within a large global collection of pathogenic Leptospira:
      implications for strain identification and molecular epidemiology.
AB  - Leptospirosis is an important zoonosis with widespread human health implications.
      The non-availability of accurate identification methods for the individualization
      of different Leptospira for outbreak investigations poses bountiful problems in
      the disease control arena. We harnessed fluorescent amplified fragment length
      polymorphism analysis (FAFLP) for Leptospira and investigated its utility in
      establishing genetic relationships among 271 isolates in the context of species
      level assignments of our global collection of isolates and strains obtained from
      a diverse array of hosts. In addition, this method was compared to an in-house
      multilocus sequence typing (MLST) method based on polymorphisms in three
      housekeeping genes, the rrs locus and two envelope proteins. Phylogenetic
      relationships were deduced based on bifurcating Neighbor-joining trees as well as
      median joining network analyses integrating both the FAFLP data and MLST based
      haplotypes. The phylogenetic relationships were also reproduced through Bayesian
      analysis of the multilocus sequence polymorphisms. We found FAFLP to be an
      important method for outbreak investigation and for clustering of isolates based
      on their geographical descent rather than by genome species types. The FAFLP
      method was, however, not able to convey much taxonomical utility sufficient to
      replace the highly tedious serotyping procedures in vogue. MLST, on the other
      hand, was found to be highly robust and efficient in identifying ancestral
      relationships and segregating the outbreak associated strains or otherwise
      according to their genome species status and, therefore, could unambiguously be
      applied for investigating phylogenetics of Leptospira in the context of taxonomy
      as well as gene flow. For instance, MLST was more efficient, as compared to FAFLP
      method, in clustering strains from the Andaman island of India, with their
      counterparts from mainland India and Sri Lanka, implying that such strains share
      genetic relationships and that leptospiral strains might be frequently
      circulating between the islands and the mainland.

PMID- 20805988
TI  - A genotype-first approach for the molecular and clinical characterization of
      uncommon de novo microdeletion of 20q13.33.
AB  - BACKGROUND: Subtelomeric deletions of the long arm of chromosome 20 are rare,
      with only 11 described in the literature. Clinical features of individuals with
      these microdeletions include severe limb malformations, skeletal abnormalities,
      growth retardation, developmental and speech delay, mental retardation, seizures
      and mild, non-specific dysmorphic features. METHODOLOGY/PRINCIPAL FINDINGS: We
      characterized microdeletions at 20q13.33 in six individuals referred for genetic
      evaluation of developmental delay, mental retardation, and/or congenital
      anomalies. A comparison to previously reported cases of 20q13.33 microdeletion
      shows phenotypic overlap, with clinical features that include mental retardation,
      developmental delay, speech and language deficits, seizures, and behavior
      problems such as autistic spectrum disorder. There does not appear to be a
      clinically recognizable constellation of dysmorphic features among individuals
      with subtelomeric 20q microdeletions. CONCLUSIONS/SIGNIFICANCE: Based on genotype
      phenotype correlation among individuals in this and previous studies, we discuss
      several possible candidate genes for specific clinical features, including
      ARFGAP1, CHRNA4 and KCNQ2 and neurodevelopmental deficits. Deletion of this
      region may play an important role in cognitive development.

PMID- 20805989
TI  - 13[C]-urea breath test as a novel point-of-care biomarker for tuberculosis
      treatment and diagnosis.
AB  - BACKGROUND: Pathogen-specific metabolic pathways may be detected by breath tests
      based on introduction of stable isotopically-labeled substrates and detection of
      labeled products in exhaled breath using portable infrared spectrometers.
      METHODOLOGY/PRINCIPAL FINDINGS: We tested whether mycobacterial urease activity
      could be utilized in such a breath test format as the basis of a novel biomarker
      and diagnostic for pulmonary TB. Sensitized New-Zealand White Rabbits underwent
      bronchoscopic infection with either Mycobacterium bovis or Mycobacterium
      tuberculosis. Rabbits were treated with 25 mg/kg of isoniazid (INH) approximately
      2 months after infection when significant cavitary lung pathology was present.
      [(13)C] urea was instilled directly into the lungs of intubated rabbits at
      selected time points, exhaled air samples analyzed, and the kinetics of
      delta(13)CO(2) formation were determined. Samples obtained prior to inoculation
      served as control samples for background (13)CO(2) conversion in the rabbit
      model. (13)CO(2), from metabolic conversion of [(13)C]-urea by mycobacterial
      urease activity, was readily detectable in the exhaled breath of infected rabbits
      within 15 minutes of administration. Analyses showed a rapid increase in the rate
      of (13)CO(2) formation both early in disease and prior to treatment with INH.
      Following INH treatment, all evaluable rabbits showed a decrease in the rate of
      (13)CO(2) formation. CONCLUSIONS/SIGNIFICANCE: Urea breath testing may provide a
      useful diagnostic and biomarker assay for tuberculosis and for treatment
      response. Future work will test specificity for M. tuberculosis using lung
      targeted dry powder inhalation formulations, combined with co-administering oral
      urease inhibitors together with a saturating oral dose of unlabeled urea, which
      would prevent the delta(13)CO(2) signal from urease-positive gastrointestinal
      organisms.

PMID- 20805990
TI  - CREB inhibits AP-2alpha expression to regulate the malignant phenotype of
      melanoma.
AB  - BACKGROUND: The loss of AP-2alpha and increased activity of cAMP-responsive
      element binding (CREB) protein are two hallmarks of malignant progression of
      cutaneous melanoma. However, the molecular mechanism responsible for the loss of
      AP-2alpha during melanoma progression remains unknown. METHODOLOGY/PRINCIPAL
      FINDINGS: Herein, we demonstrate that both inhibition of PKA-dependent CREB
      phosphorylation, as well as silencing of CREB expression by shRNA, restored AP
      2alpha protein expression in two metastatic melanoma cell lines. Moreover, rescue
      of CREB expression in CREB-silenced cell lines downregulates expression of AP
      2alpha. Loss of AP-2alpha expression in metastatic melanoma occurs via a dual
      mechanism involving binding of CREB to the AP-2alpha promoter and CREB-induced
      overexpression of another oncogenic transcription factor, E2F-1. Upregulation of
      AP-2alpha expression following CREB silencing increases endogenous p21(Waf1) and
      decreases MCAM/MUC18, both known to be downstream target genes of AP-2alpha
      involved in melanoma progression. CONCLUSIONS/SIGNIFICANCE: Since AP-2alpha
      regulates several genes associated with the metastatic potential of melanoma
      including c-KIT, VEGF, PAR-1, MCAM/MUC18, and p21(Waf1), our data identified CREB
      as a major regulator of the malignant melanoma phenotype.

PMID- 20805992
TI  - In vitro transformation of primary human CD34+ cells by AML fusion oncogenes:
      early gene expression profiling reveals possible drug target in AML.
AB  - Different fusion oncogenes in acute myeloid leukemia (AML) have distinct clinical
      and laboratory features suggesting different modes of malignant transformation.
      Here we compare the in vitro effects of representatives of 4 major groups of AML
      fusion oncogenes on primary human CD34+ cells. As expected from their clinical
      similarities, MLL-AF9 and NUP98-HOXA9 had very similar effects in vitro. They
      both caused erythroid hyperplasia and a clear block in erythroid and myeloid
      maturation. On the other hand, AML1-ETO and PML-RARA had only modest effects on
      myeloid and erythroid differentiation. All oncogenes except PML-RARA caused a
      dramatic increase in long-term proliferation and self-renewal. Gene expression
      profiling revealed two distinct temporal patterns of gene deregulation. Gene
      deregulation by MLL-AF9 and NUP98-HOXA9 peaked 3 days after transduction. In
      contrast, the vast majority of gene deregulation by AML1-ETO and PML-RARA
      occurred within 6 hours, followed by a dramatic drop in the numbers of
      deregulated genes. Interestingly, the p53 inhibitor MDM2 was upregulated by AML1
      ETO at 6 hours. Nutlin-3, an inhibitor of the interaction between MDM2 and p53,
      specifically inhibited the proliferation and self-renewal of primary human CD34+
      cells transduced with AML1-ETO, suggesting that MDM2 upregulation plays a role in
      cell transformation by AML1-ETO. These data show that differences among AML
      fusion oncogenes can be recapitulated in vitro using primary human CD34+ cells
      and that early gene expression profiling in these cells can reveal potential drug
      targets in AML.

PMID- 20805993
TI  - Intracellular conversion of environmental nitrate and nitrite to nitric oxide
      with resulting developmental toxicity to the crustacean Daphnia magna.
AB  - BACKGROUND: Nitrate and nitrite (jointly referred to herein as NO(x)) are
      ubiquitous environmental contaminants to which aquatic organisms are at
      particularly high risk of exposure. We tested the hypothesis that NO(x) undergo
      intracellular conversion to the potent signaling molecule nitric oxide resulting
      in the disruption of endocrine-regulated processes. METHODOLOGY/PRINCIPAL
      FINDINGS: These experiments were performed with insect cells (Drosophila S2) and
      whole organisms Daphnia magna. We first evaluated the ability of cells to convert
      nitrate (NO(3)(-)) and nitrite (NO(2)(-)) to nitric oxide using amperometric real
      time nitric oxide detection. Both NO(3)(-) and NO(2)(-) were converted to nitric
      oxide in a substrate concentration-dependent manner. Further, nitric oxide
      trapping and fluorescent visualization studies revealed that perinatal daphnids
      readily convert NO(2)(-) to nitric oxide. Next, daphnids were continuously
      exposed to concentrations of the nitric oxide-donor sodium nitroprusside
      (positive control) and to concentrations of NO(3)(-) and NO(2)(-). All three
      compounds interfered with normal embryo development and reduced daphnid
      fecundity. Developmental abnormalities were characteristic of those elicited by
      compounds that interfere with ecdysteroid signaling. However, no compelling
      evidence was generated to indicate that nitric oxide reduced ecdysteroid titers.
      CONCLUSIONS/SIGNIFICANCE: Results demonstrate that nitrite elicits developmental
      and reproductive toxicity at environmentally relevant concentrations due likely
      to its intracellular conversion to nitric oxide.

PMID- 20805991
TI  - Autonomous bioluminescent expression of the bacterial luciferase gene cassette
      (lux) in a mammalian cell line.
AB  - BACKGROUND: The bacterial luciferase (lux) gene cassette consists of five genes
      (luxCDABE) whose protein products synergistically generate bioluminescent light
      signals exclusive of supplementary substrate additions or exogenous
      manipulations. Historically expressible only in prokaryotes, the lux operon was
      re-synthesized through a process of multi-bicistronic, codon-optimization to
      demonstrate for the first time self-directed bioluminescence emission in a
      mammalian HEK293 cell line in vitro and in vivo. METHODOLOGY/PRINCIPAL FINDINGS:
      Autonomous in vitro light production was shown to be 12-fold greater than the
      observable background associated with untransfected control cells. The
      availability of reduced riboflavin phosphate (FMNH(2)) was identified as the
      limiting bioluminescence substrate in the mammalian cell environment even after
      the addition of a constitutively expressed flavin reductase gene (frp) from
      Vibrio harveyi. FMNH(2) supplementation led to a 151-fold increase in
      bioluminescence in cells expressing mammalian codon-optimized luxCDE and frp
      genes. When injected subcutaneously into nude mice, in vivo optical imaging
      permitted near instantaneous light detection that persisted independently for the
      60 min length of the assay with negligible background. CONCLUSIONS/SIGNIFICANCE:
      The speed, longevity, and self-sufficiency of lux expression in the mammalian
      cellular environment provides a viable and powerful alternative for real-time
      target visualization not currently offered by existing bioluminescent and
      fluorescent imaging technologies.

PMID- 20805994
TI  - Proteomics comparison of cerebrospinal fluid of relapsing remitting and primary
      progressive multiple sclerosis.
AB  - BACKGROUND: Based on clinical representation of disease symptoms multiple
      sclerosis (MScl) patients can be divided into two major subtypes; relapsing
      remitting (RR) MScl (85-90%) and primary progressive (PP) MScl (10-15%).
      Proteomics analysis of cerebrospinal fluid (CSF) has detected a number of
      proteins that were elevated in MScl patients. Here we specifically aimed to
      differentiate between the PP and RR subtypes of MScl by comparing CSF proteins.
      METHODOLOGY/PRINCIPAL FINDINGS: CSF samples (n = 31) were handled according to
      the same protocol for quantitative mass spectrometry measurements we reported
      previously. In the comparison of PP MScl versus RR MScl we observed a number of
      differentially abundant proteins, such as protein jagged-1 and vitamin D-binding
      protein. Protein jagged-1 was over three times less abundant in PP MScl compared
      to RR MScl. Vitamin D-binding protein was only detected in the RR MScl samples.
      These two proteins were validated by independent techniques (western blot and
      ELISA) as differentially abundant in the comparison between both MScl types.
      CONCLUSIONS/SIGNIFICANCE: The main finding of this comparative study is the
      observation that the proteome profiles of CSF in PP and RR MScl patients overlap
      to a large extent. Still, a number of differences could be observed. Protein
      jagged-1 is a ligand for multiple Notch receptors and involved in the mediation
      of Notch signaling. It is suggested in literature that the Notch pathway is
      involved in the remyelination of MScl lesions. Aberration of normal homeostasis
      of Vitamin D, of which approximately 90% is bound to vitamin D-binding protein,
      has been widely implicated in MScl for some years now. Vitamin D directly and
      indirectly regulates the differentiation, activation of CD4+ T-lymphocytes and
      can prevent the development of autoimmune processes, and so it may be involved in
      neuroprotective elements in MScl.

PMID- 20805995
TI  - Loss of p19(Arf) facilitates the angiogenic switch and tumor initiation in a
      multi-stage cancer model via p53-dependent and independent mechanisms.
AB  - The Arf tumor suppressor acts as a sensor of oncogenic signals, countering
      aberrant proliferation in large part via activation of the p53 transcriptional
      program, though a number of p53-independent functions have been described.
      Mounting evidence suggests that, in addition to promoting tumorigenesis via
      disruptions in the homeostatic balance between cell proliferation and apoptosis
      of overt cancer cells, genetic alterations leading to tumor suppressor loss of
      function or oncogene gain of function can also incite tumor development via
      effects on the tumor microenvironment. In a transgenic mouse model of multi-stage
      pancreatic neuroendocrine carcinogenesis (PNET) driven by inhibition of the
      canonical p53 and Rb tumor suppressors with SV40 large T-antigen (Tag),
      stochastic progression to tumors is limited in part by a requirement for
      initiation of an angiogenic switch. Despite inhibition of p53 by Tag in this
      mouse PNET model, concomitant disruption of Arf via genetic knockout resulted in
      a significantly accelerated pathway to tumor formation that was surprisingly not
      driven by alterations in tumor cell proliferation or apoptosis, but rather via
      earlier activation of the angiogenic switch. In the setting of a constitutional
      p53 gene knockout, loss of Arf also accelerated tumor development, albeit to a
      lesser degree. These findings demonstrate that Arf loss of function can promote
      tumorigenesis via facilitating angiogenesis, at least in part, through p53
      independent mechanisms.

PMID- 20805996
TI  - In vivo binding and retention of CD4-specific DARPin 57.2 in macaques.
AB  - BACKGROUND: The recently described Designed Ankyrin Repeat Protein (DARPin)
      technology can produce highly selective ligands to a variety of biological
      targets at a low production cost. METHODOLOGY/PRINCIPAL FINDINGS: To investigate
      the in vivo use of DARPins for future application to novel anti-HIV strategies,
      we identified potent CD4-specific DARPins that recognize rhesus CD4 and followed
      the fate of intravenously injected CD4-specific DARPin 57.2 in rhesus macaques.
      The human CD4-specific DARPin 57.2 bound macaque CD4(+) cells and exhibited
      potent inhibitory activity against SIV infection in vitro. DARPin 57.2 or the
      control E3_5 DARPin was injected into rhesus macaques and the fate of cell-free
      and cell-bound CD4-specific DARPin was evaluated. DARPin-bound CD4(+) cells were
      detected in the peripheral blood as early as 30 minutes after the injection,
      decreasing within 6 hours and being almost undetectable within 24 hours. The
      amount of DARPin bound was dependent on the amount of DARPin injected. CD4
      specific DARPin was also detected on CD4(+) cells in the lymph nodes within 30
      minutes, which persisted with similar kinetics to blood. More extensive analysis
      using blood revealed that DARPin 57.2 bound to all CD4(+) cell types (T cells,
      monocytes, dendritic cells) in vivo and in vitro with the amount of binding
      directly proportional to the amount of CD4 on the cell surface. Cell-free DARPins
      were also detected in the plasma, but were rapidly cleared from circulation.
      CONCLUSIONS/SIGNIFICANCE: We demonstrated that the CD4-specific DARPin can
      rapidly and selectively bind its target cells in vivo, warranting further studies
      on possible clinical use of the DARPin technology.

PMID- 20805997
TI  - Caenorhabditis elegans operons contain a higher proportion of genes with multiple
      transcripts and use 3' splice sites differentially.
AB  - RNA splicing generates multiple transcript isoforms from a single gene and
      enhances the complexity of eukaryotic gene expression. In some eukaryotes, operon
      exists as an ancient regulatory mechanism of gene expression that requires strict
      positional and regulatory relationships among its genes. It remains unknown
      whether operonic genes generate transcript isoforms in a similar manner as non
      operonic genes do, the expression of which is less likely limited by their
      positions and relationships with surrounding genes. We analyzed the number of
      transcript isoforms of Caenorhabditis elegans operonic genes and found that C.
      elegans operons contain a much higher proportion of genes with multiple
      transcript isoforms than non-operonic genes do. For genes that express multiple
      transcript isoforms, there is no apparent difference between the number of
      isoforms in operonic and non-operonic genes. C. elegans operonic genes also have
      a different preference of the 20 most common 3' splice sites compared to non
      operonic genes. Our analyses suggest that C. elegans operons enhance expression
      complexity by increasing the proportion of genes that express multiple transcript
      isoforms and maintain splicing efficiency by differential use of common 3' splice
      sites.

PMID- 20805999
TI  - Patterning nanowire and micro-nanoparticle array on micropillar-structured
      surface: Experiment and modeling.
AB  - DNA molecules in a solution can be immobilized and stretched into a highly
      ordered array on a solid surface containing micropillars by molecular combing
      technique. However, the mechanism of this process is not well understood. In this
      study, we demonstrated the generation of DNA nanostrand array with linear,
      zigzag, and fork-zigzag patterns and the microfluidic processes are modeled based
      on a deforming body-fitted grid approach. The simulation results provide insights
      for explaining the stretching, immobilizing, and patterning of DNA molecules
      observed in the experiments.

PMID- 20805998
TI  - Epithelial to mesenchymal transition is mechanistically linked with stem cell
      signatures in prostate cancer cells.
AB  - BACKGROUND: Current management of patients diagnosed with prostate cancer (PCa)
      is very effective; however, tumor recurrence with Castrate Resistant Prostate
      Cancer (CRPC) and subsequent metastasis lead to poor survival outcome, suggesting
      that there is a dire need for novel mechanistic understanding of tumor
      recurrence, which would be critical for designing novel therapies. The recurrence
      and the metastasis of PCa are tightly linked with the biology of prostate cancer
      stem cells or cancer-initiating cells that is reminiscent of the acquisition of
      Epithelial to Mesenchymal Transition (EMT) phenotype. Increasing evidence
      suggests that EMT-type cells share many biological characteristics with cancer
      stem-like cells. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we found that PCa
      cells with EMT phenotype displayed stem-like cell features characterized by
      increased expression of Sox2, Nanog, Oct4, Lin28B and/or Notch1, consistent with
      enhanced clonogenic and sphere (prostasphere)-forming ability and tumorigenecity
      in mice, which was associated with decreased expression of miR-200 and/or let-7
      family. Reversal of EMT by re-expression of miR-200 inhibited prostasphere
      forming ability of EMT-type cells and reduced the expression of Notch1 and
      Lin28B. Down-regulation of Lin28B increased let-7 expression, which was
      consistent with repressed self-renewal capability. CONCLUSIONS/SIGNIFICANCE:
      These results suggest that miR-200 played a pivotal role in linking the
      characteristics of cancer stem-like cells with EMT-like cell signatures in PCa.
      Selective elimination of cancer stem-like cells by reversing the EMT phenotype to
      Mesenchymal-Epithelial Transition (MET) phenotype using novel agents would be
      useful for the prevention of tumor recurrence especially by eliminating those
      cells that are the "Root Cause" of tumor development and recurrence.

PMID- 20806000
TI  - A dielectrophoretic chip with a roughened metal surface for on-chip surface
      enhanced Raman scattering analysis of bacteria.
AB  - We present an analysis of the results of in situ surface-enhanced Raman
      scattering (SERS) of bacteria using a microfluidic chip capable of continuously
      sorting and concentrating bacteria via three-dimensional dielectrophoresis (DEP).
      Microchannels were made by sandwiching DEP microelectrodes between two glass
      slides. Avoiding the use of a metal nanoparticle suspension, a roughened metal
      surface is integrated into the DEP-based microfluidic chip for on-chip SERS
      detection of bacteria. On the upper surface of the slide, a roughened metal
      shelter was settled in front of the DEP concentrator to enhance Raman scattering.
      Similarly, an electrode-patterned bottom layer fabricated on a thin cover-slip
      was used to reduce fluorescence noise from the glass substrate. Gram positive
      (Staphylococcus aureus) and Gram negative (Pseudomonas aeruginosa) bacteria were
      effectively distinguished in the SERS spectral data. Staphylococcus aureus
      (concentration of 10(6) CFUml) was continuously separated and concentrated via
      DEP out of a sample of blood cells. At a flow rate of 1 mulmin, the bacteria were
      highly concentrated at the roughened surface and ready for on-chip SERS analysis
      within 3 min. The SERS data were successfully amplified by one order of magnitude
      and analyzed within a few minutes, resulting in the detection of signature peaks
      of the respective bacteria.

PMID- 20806001
TI  - Composition and phase dependence of the intrinsic and extrinsic piezoelectric
      activity of domain engineered (1-x)Pb(Mg(13)Nb(23))O(3)-xPbTiO(3) crystals.
AB  - The piezoelectric response of [001] poled domain engineered (1
      x)Pb(Mg(13)Nb(23))O(3)-xPbTiO(3) (PMN-PT) crystals was investigated as a function
      of composition and phase using Rayleigh analysis. The results revealed that the
      intrinsic (reversible) contribution plays a dominant role in the high
      piezoelectric activity for PMN-PT crystals. The intrinsic piezoelectric response
      of the monoclinic (M(C)) PMN-xPT crystals, 0.31</=x</=0.35, exhibited peak values
      for compositions close to R-M(C) and M(C)-T phase boundaries, however, being less
      than 2000 pCN. In the rhombohedral phase region, x</=0.30, the intrinsic
      piezoelectric response was found to increase as the composition approached the
      rhombohedral-monoclinic (R-M(C)) phase boundary. The maximum piezoelectric
      response was observed in rhombohedral PMN-0.30PT crystals, being on the order of
      2500 pCN. This ultrahigh piezoelectric response was determined to be related to
      the high shear piezoelectric activity of single domain state, corresponding to an
      ease in polarization rotation, for compositions close to a morphotropic phase
      boundary (MPB). The role of monoclinic phase is only to form a MPB with R phase,
      but not directly contribute to the ultrahigh piezoelectric activity in
      rhombohedral PMN-0.30PT crystals. The extrinsic contribution to piezoelectric
      activity was found to be less than 5% for the compositions away from R-M(C) and
      M(C)-T phase boundaries, due to a stable domain engineered structure. As the
      composition approached MPBs, the extrinsic contribution increased slightly
      (<10%), due to the enhanced motion of phase boundaries.

PMID- 20806002
TI  - Redescription of the tintinnid ciliate Tintinnopsis fimbriata Meunier, 1919
      (Spirotricha, Choreotrichida) from coastal waters of Northern Germany.
AB  - The tintinnid ciliate Tintinnopsis fimbriata Meunier, 1919 is mainly distributed
      in mesohaline coastal waters of Arctic, temperate, and subtropical regions. Since
      its cytological features were unknown, the species is redescribed and neotypified
      from material collected in coastal waters of the North Sea near the Island of
      Sylt (Northern Germany), using live observation and protargol impregnation. The
      species diagnosis is improved to include the new characteristics, e.g., the
      somatic ciliary pattern comprising a ventral, dorsal, and posterior kinety as
      well as a right, left, and lateral ciliary field. Due to the complex somatic
      ciliary pattern, T. fimbriata belongs to a diverse group of highly developed
      tintinnids with which it shares the hypoapokinetal development of the oral
      primordium posterior to the lateral ciliary field.

PMID- 20806003
TI  - Species concepts in Calonectria (Cylindrocladium).
AB  - Species of Calonectria and their Cylindrocladium anamorphs are important plant
      pathogens worldwide. At present 52 Cylindrocladium spp. and 37 Calonectria spp.
      are recognised based on sexual compatibility, morphology and phylogenetic
      inference. The polyphasic approach of integrating Biological, Morphological and
      Phylogenetic Species Concepts has revolutionised the taxonomy of fungi. This
      review aims to present an overview of published research on the genera
      Calonectria and Cylindrocladium as they pertain to their taxonomic history. The
      nomenclature as well as future research necessary for this group of fungi are
      also briefly discussed.

PMID- 20806004
TI  - Multigene phylogeny and mating tests reveal three cryptic species related to
      Calonectria pauciramosa.
AB  - Calonectria pauciramosa is a pathogen of numerous plant hosts worldwide. Recent
      studies have indicated that it included cryptic species, some of which are
      identified in this study. Isolates from various geographical origins were
      collected and compared based on morphology, DNA sequence data of the beta
      tubulin, histone H3 and translation elongation factor-1alpha regions and mating
      compatibility. Comparisons of the DNA sequence data and mating compatibility
      revealed three new species. These included Ca. colombiana sp. nov. from Colombia,
      Ca. polizzii sp. nov. from Italy and Ca. zuluensis sp. nov. from South Africa,
      all of which had distinguishing morphological features. Based on DNA sequence
      data, Ca. brasiliensis is also elevated to species level.

PMID- 20806005
TI  - Phylogeny and systematics of the genus Calonectria.
AB  - Species of Calonectria are important plant pathogens, several of which have a
      worldwide distribution. Contemporary taxonomic studies on these fungi have
      chiefly relied on DNA sequence comparisons of the beta-tubulin gene region.
      Despite many new species being described, there has been no phylogenetic
      synthesis for the group since the last monographic study almost a decade ago. In
      the present study, the identity of a large collection of Calonectria isolates
      from various geographic regions was determined using morphological and DNA
      sequence comparisons. This resulted in the discovery of seven new species; Ca.
      densa, Ca. eucalypti, Ca. humicola, Ca. orientalis, Ca. pini, Ca. pseudoscoparia
      and Ca. sulawesiensis, bringing the total number of currently accepted
      Calonectria species to 68. A multigene phylogeny was subsequently constructed for
      all available Calonectria spp., employing seven gene regions, namely actin, beta
      tubulin, calmodulin, histone H3, the internal transcribed spacer regions 1 and 2
      and the 5.8S gene of the ribosomal RNA, 28S large subunit RNA gene and
      translation elongation 1-alpha. Based on these data 13 phylogenetic groups could
      be distinguished within the genus Calonectria that correlated with morphological
      features. Dichotomous and synoptic keys to all Calonectria spp. currently
      recognised are also provided.

PMID- 20806006
TI  - Emerging structures and ligands for P2X(3) and P2X(4) receptors-towards novel
      treatments of neuropathic pain.

PMID- 20806007
TI  - Purinergic Signalling special issue on "Purinergic Signalling in the Inner Ear";
      a commentary by Professor Geoffrey Burnstock, Editor-in-Chief.

PMID- 20806008
TI  - Purinergic signalling in the inner ear-perspectives and progress.

PMID- 20806009
TI  - ATP-induced morphological changes in supporting cells of the developing cochlea.
AB  - The developing cochlea of mammals contains a large group of columnar-shaped
      cells, which together form a structure known as Kolliker's organ. Prior to the
      onset of hearing, these inner supporting cells periodically release adenosine 5'
      triphosphate (ATP), which activates purinergic receptors in surrounding
      supporting cells, inner hair cells and the dendrites of primary auditory neurons.
      Recent studies indicate that purinergic signaling between inner supporting cells
      and inner hair cells initiates bursts of action potentials in auditory nerve
      fibers before the onset of hearing. ATP also induces prominent effects in inner
      supporting cells, including an increase in membrane conductance, a rise in
      intracellular Ca(2+), and dramatic changes in cell shape, although the importance
      of ATP signaling in non-sensory cells of the developing cochlea remains unknown.
      Here, we review current knowledge pertaining to purinergic signaling in
      supporting cells of Kolliker's organ and focus on the mechanisms by which ATP
      induces changes in their morphology. We show that these changes in cell shape are
      preceded by increases in cytoplasmic Ca(2+), and provide new evidence indicating
      that elevation of intracellular Ca(2+) and IP(3) are sufficient to initiate shape
      changes. In addition, we discuss the possibility that these ATP-mediated
      morphological changes reflect crenation following the activation of Ca(2+)
      activated Cl(-) channels, and speculate about the possible functions of these
      changes in cell morphology for maturation of the cochlea.

PMID- 20806011
TI  - Damage-induced cell-cell communication in different cochlear cell types via two
      distinct ATP-dependent Ca waves.
AB  - Intercellular Ca(2+) waves can coordinate the action of large numbers of cells
      over significant distances. Recent work in many different systems has indicated
      that the release of ATP is fundamental for the propagation of most Ca(2+) waves.
      In the organ of hearing, the cochlea, ATP release is involved in critical
      signalling events during tissue maturation. ATP-dependent signalling is also
      implicated in the normal hearing process and in sensing cochlear damage. Here, we
      show that two distinct Ca(2+) waves are triggered during damage to cochlear
      explants. Both Ca(2+) waves are elicited by extracellular ATP acting on P2
      receptors, but they differ in their source of Ca(2+), their velocity, their
      extent of spread and the cell type through which they propagate. A slower Ca(2+)
      wave (14 mum/s) communicates between Deiters' cells and is mediated by P2Y
      receptors and Ca(2+) release from IP(3)-sensitive stores. In contrast, a faster
      Ca(2+) wave (41 mum/s) propagates through sensory hair cells and is mediated by
      Ca(2+) influx from the external environment. Using inhibitors and selective
      agonists of P2 receptors, we suggest that the faster Ca(2+) wave is mediated by
      P2X(4) receptors. Thus, in complex tissues, the expression of different receptors
      determines the propagation of distinct intercellular communication signals.
      ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article
      (doi:10.1007/s11302-010-9193-8) contains supplementary material, which is
      available to authorized users.

PMID- 20806010
TI  - ATP-mediated cell-cell signaling in the organ of Corti: the role of connexin
      channels.
AB  - Connexin 26 (Cx26) and connexin 30 (Cx30) form hemichannels that release ATP from
      the endolymphatic surface of cochlear supporting and epithelial cells and also
      form gap junction (GJ) channels that allow the concomitant intercellular
      diffusion of Ca(2+) mobilizing second messengers. Released ATP in turn activates
      G-protein coupled P2Y(2) and P2Y(4) receptors, PLC-dependent generation of IP(3),
      release of Ca(2+) from intracellular stores, instigating the regenerative
      propagation of intercellular Ca(2+) signals (ICS). The range of ICS propagation
      is sensitive to the concentration of extracellular divalent cations and activity
      of ectonucleotidases. Here, the expression patterns of Cx26 and Cx30 were
      characterized in postnatal cochlear tissues obtained from mice aged between P5
      and P6. The expression gradient along the longitudinal axis of the cochlea,
      decreasing from the basal to the apical cochlear turn (CT), was more pronounced
      in outer sulcus (OS) cells than in inner sulcus (IS) cells. GJ-mediated dye
      coupling was maximal in OS cells of the basal CT, inhibited by the nonselective
      connexin channel blocker carbenoxolone (CBX) and absent in hair cells.
      Photostimulating OS cells with caged inositol (3,4,5) tri-phosphate (IP(3))
      resulted in transfer of ICS in the lateral direction, from OS cells to IS cells
      across the hair cell region (HCR) of medial and basal CTs. ICS transfer in the
      opposite (medial) direction, from IS cells photostimulated with caged IP(3) to OS
      cells, occurred mostly in the basal CT. In addition, OS cells displayed
      impressive rhythmic activity with oscillations of cytosolic free Ca(2+)
      concentration ([Ca(2+)](i)) coordinated by the propagation of Ca(2+) wavefronts
      sweeping repeatedly through the same tissue area along the coiling axis of the
      cochlea. Oscillations evoked by uncaging IP(3) or by applying ATP differed
      greatly, by as much as one order of magnitude, in frequency and waveform rise
      time. ICS evoked by direct application of ATP propagated along convoluted
      cellular paths in the OS, which often branched and changed dynamically over time.
      Potential implications of these findings are discussed in the context of
      developmental regulation and cochlear pathophysiology. ELECTRONIC SUPPLEMENTARY
      MATERIAL: The online version of this article (doi:10.1007/s11302-010-9192-9)
      contains supplementary material, which is available to authorized users.

PMID- 20806012
TI  - Purinergic signaling in cochleovestibular hair cells and afferent neurons.
AB  - Purinergic signaling in the mammalian cochleovestibular hair cells and afferent
      neurons is reviewed. The scope includes P2 and P1 receptors in the inner hair
      cells (IHCs) of the cochlea, the type I spiral ganglion neurons (SGNs) that
      convey auditory signals from IHCs, the vestibular hair cells (VHCs) in the
      vestibular end organs (macula in the otolith organs and crista in the
      semicircular canals), and the vestibular ganglion neurons (VGNs) that transmit
      postural and rotatory information from VHCs. Various subtypes of P2X ionotropic
      receptors are expressed in IHCs as well as P2Y metabotropic receptors that
      mobilize intracellular calcium. Their functional roles still remain speculative,
      but adenosine 5'-triphosphate (ATP) could regulate the spontaneous activity of
      the hair cells during development and the receptor potentials of mature hair
      cells during sound stimulation. In SGNs, P2Y metabotropic receptors activate a
      nonspecific cation conductance that is permeable to large cations as NMDG(+) and
      TEA(+). Remarkably, this depolarizing nonspecific conductance in SGNs can also be
      activated by other metabotropic processes evoked by acetylcholine and tachykinin.
      The molecular nature and the role of this depolarizing channel are unknown, but
      its electrophysiological properties suggest that it could lie within the
      transient receptor potential channel family and could regulate the firing
      properties of the afferent neurons. Studies on the vestibular partition (VHC and
      VGN) are sparse but have also shown the expression of P2X and P2Y receptors.
      There is still little evidence of functional P1 (adenosine) receptors in the
      afferent system of the inner ear.

PMID- 20806014
TI  - ATP-mediated potassium recycling in the cochlear supporting cells.
AB  - Gap junction-mediated K(+) recycling in the cochlear supporting cell has been
      proposed to play a critical role in hearing. However, how potassium ions enter
      into the supporting cells to recycle K(+) remains undetermined. In this paper, we
      report that ATP can mediate K(+) sinking to recycle K(+) in the cochlear
      supporting cells. We found that micromolar or submicromolar levels of ATP could
      evoke a K(+)-dependent inward current in the cochlear supporting cells. At
      negative membrane potentials and the resting membrane potential of -80 mV, the
      amplitude of the ATP-evoked inward current demonstrated a linear relationship to
      the extracellular concentration of K(+), increasing as the extracellular
      concentration of K(+) increased. The inward current also increased as the
      concentration of ATP was increased. In the absence of ATP, there was no evoked
      inward current for extracellular K(+) challenge in the cochlear supporting cells.
      The ATP-evoked inward current could be inhibited by ionotropic purinergic (P2X)
      receptor antagonists. Application of pyridoxalphosphate-6-azophenyl-2',4'
      disulfonic acid (PPADS, 50 microM) or pre-incubation with an irreversible P2X7
      antagonist oxidized ATP (oATP, 0.1 mM) completely abolished the ATP-evoked inward
      current at the negative membrane potential. ATP also evoked an inward current at
      cell depolarization, which could be inhibited by intracellular Cs(+) and
      eliminated by positive holding potentials. Our data indicate that ATP can
      activate P2X receptors to recycle K(+) in the cochlear supporting cells at the
      resting membrane potential under normal physiological and pathological
      conditions. This ATP-mediated K(+) recycling may play an important role in the
      maintenance of cochlear ionic homeostasis. ELECTRONIC SUPPLEMENTARY MATERIAL: The
      online version of this article (doi:10.1007/s11302-010-9184-9) contains
      supplementary material, which is available to authorized users.

PMID- 20806013
TI  - Role of nitric oxide on purinergic signalling in the cochlea.
AB  - In the inner ear, there is considerable evidence that extracellular adenosine 5'
      triphosphate (ATP) plays an important role in auditory neurotransmission as a
      neurotransmitter or a neuromodulator, although the potential role of adenosine
      signalling in the modulation of auditory neurotransmission has also been
      reported. The activation of ligand-gated ionotropic P2X receptors and G protein
      coupled metabotropic P2Y receptors has been reported to induce an increase of
      intracellular Ca(2+) concentration ([Ca(2+)](i)) in inner hair cells (IHCs),
      outer hair cells (OHCs), spiral ganglion neurons (SGNs), and supporting cells in
      the cochlea. ATP may participate in auditory neurotransmission by modulating
      [Ca(2+)](i) in the cochlear cells. Recent studies showed that extracellular ATP
      induced nitric oxide (NO) production in IHCs, OHCs, and SGNs, which affects the
      ATP-induced Ca(2+) response via the NO-cGMP-PKG pathway in those cells by a
      feedback mechanism. A cross-talk between NO and ATP may therefore exist in the
      auditory signal transduction. In the present article, I review the role of NO on
      the ATP-induced Ca(2+) signalling in IHCs and OHCs. I also consider the possible
      role of NO in the ATP-induced Ca(2+) signalling in SGNs and supporting cells.

PMID- 20806015
TI  - Differential expression of P2Y receptors in the rat cochlea during development.
AB  - Purinergic signaling has broad physiological significance to the hearing organ,
      involving signal transduction via ionotropic P2X receptors and metabotropic G
      protein-coupled P2Y and P1 (adenosine), alongside conversion of nucleotides and
      nucleosides by ecto-nucleotidases and ecto-nucleoside diphosphokinase. In
      addition, ATP release is modulated by acoustic overstimulation or stress and
      involves feedback regulation. Many of these principal elements of the purinergic
      signaling complex have been well characterized in the cochlea, while the
      characterization of P2Y receptor expression is emerging. The present study used
      immunohistochemistry to evaluate the expression of five P2Y receptors, P2Y(1),
      P2Y(2), P2Y(4), P2Y(6), and P2Y(12), during development of the rat cochlea.
      Commencing in the late embryonic period, the P2Y receptors studied were found in
      the cells lining the cochlear partition, associated with establishment of the
      electrochemical environment which provides the driving force for sound
      transduction. In addition, early postnatal P2Y(2) and P2Y(4) protein expression
      in the greater epithelial ridge, part of the developing hearing organ, supports
      the view that initiation and regulation of spontaneous activity in the hair cells
      prior to hearing onset is mediated by purinergic signaling. Sub-cellular
      compartmentalization of P2Y receptor expression in sensory hair cells, and
      diversity of receptor expression in the spiral ganglion neurons and their
      satellite cells, indicates roles for P2Y receptor-mediated Ca(2+)-signaling in
      sound transduction and auditory neuron excitability. Overall, the dynamics of P2Y
      receptor expression during development of the cochlea complement the other
      elements of the purinergic signaling complex and reinforce the significance of
      extracellular nucleotide and nucleoside signaling to hearing.

PMID- 20806016
TI  - Distribution of NTPDase5 and NTPDase6 and the regulation of P2Y receptor
      signalling in the rat cochlea.
AB  - Membrane-bound ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) in
      the inner ear regulate complex extracellular purinergic type-2 (P2) receptor
      signalling pathways through hydrolysis of extracellular nucleoside 5'
      triphosphates and diphosphates. This study investigated the distribution of
      NTPDase5 and NTPDase6, two intracellular members of the E-NTPDase family, and
      linked this to regulation of P2 receptor signalling in the adult rat cochlea.
      These extracellular ectonucleotidases preferentially hydrolyse nucleoside 5'
      diphosphates such as UDP and GDP. Expression of both enzymes at mRNA and protein
      level was detected in cochlear tissues and there was in vivo release of soluble
      NTPDase5 and 6 into cochlear fluids. Strong NTPDase5 immunostaining was found in
      the spiral ganglion neurones and supporting Deiters' cells of the organ of Corti,
      while NTPDase6 was confined to the inner hair cells. Upregulation of NTPDase5
      after exposure to loud sound indicates a dynamic role for NTPDase5 in cochlear
      response to stress, whereas NTPDase6 may have more limited extracellular roles.
      Noise-induced upregulation of co-localised UDP-preferring P2Y(6) receptors in the
      spiral ganglion neurons further supports the involvement of NTPDase5 in
      regulation of P2Y receptor signalling. Noise stress also induced P2Y(14) (UDP-
      and UDP-glucose preferring) receptor expression in the root processes of the
      outer sulcus cells, but this was not associated with localization of the E
      NTPDases.

PMID- 20806017
TI  - Reduced P2x(2) receptor-mediated regulation of endocochlear potential in the
      ageing mouse cochlea.
AB  - Extracellular adenosine triphosphate (ATP) has profound effects on the cochlea,
      including an effect on the regulation of the endocochlear potential (EP). Noise
      induced release of ATP into the endolymph activates a shunt conductance mediated
      by P2X(2) receptors in tissues lining the endolymphatic compartment, which
      reduces the EP and, consequentially, hearing sensitivity. This may be a mechanism
      of adaptation or protection from high sound levels. As inaction of such a process
      could contribute to hearing loss, this study examined whether the action of ATP
      on EP changes with age and noise exposure in the mouse. The EP and the
      endolymphatic compartment resistance (CoPR) were measured in mice (CBA/CaJ) aged
      between 3 and 15 months. The EP and CoPR declined slightly with age with an
      associated small, but significant, reduction in auditory brainstem response
      thresholds. ATP (100-1,000 muM) microinjected into the endolymphatic compartment
      caused a dose-dependent decline in EP correlated to a similar decrease in CoPR.
      This was blocked by pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate, consistent
      with a P2X(2) receptor-mediated shunt conductance. There was no substantial
      difference in the ATP response with age. Noise exposure (octave-band noise 80-100
      decibels sound pressure level (dBSPL), 48 h) in young animals induced an
      upregulation of the P2X(2) receptor expression in the organ of Corti and spiral
      limbus, most noticeably with the 90-dB exposure. This did not occur in the aged
      animals except following exposure at 90 dBSPL. The EP response to ATP was muted
      in the noise-exposed aged animals except following the 90-dB exposure. These
      findings provide some evidence that the adaptive response of the cochlea to noise
      may be reduced in older animals, and it is speculated that this could increase
      their susceptibility to noise-induced injury.

PMID- 20806019
TI  - The history of National Purine Clubs and the International Purine Club.

PMID- 20806018
TI  - Adenosine amine congener mitigates noise-induced cochlear injury.
AB  - Hearing loss from noise exposure is a leading occupational disease, with up to 5%
      of the population at risk world-wide. Here, we present a novel purine-based
      pharmacological intervention that can ameliorate noise-induced cochlear injury.
      Wistar rats were exposed to narrow-band noise (8-12 kHz, 110 dB SPL, 2-24 h) to
      induce cochlear damage and permanent hearing loss. The selective adenosine A(1)
      receptor agonist, adenosine amine congener (ADAC), was administered
      intraperitoneally (100 microg/kg/day) at time intervals after noise exposure.
      Hearing thresholds were assessed using auditory brainstem responses and the hair
      cell loss was evaluated by quantitative histology. Free radical damage in the
      organ of Corti was assessed using nitrotyrosine immunohistochemistry. The
      treatment with ADAC after noise exposure led to a significantly greater recovery
      of hearing thresholds compared with controls. These results were upheld by
      increased survival of sensory hair cells and reduced nitrotyrosine
      immunoreactivity in ADAC-treated cochlea. We propose that ADAC could be a
      valuable treatment for noise-induced cochlear injury in instances of both acute
      and extended noise exposures.

PMID- 20806020
TI  - The German Research Unit "Neuronal and glial P2 receptors; molecular basis and
      functional significance".

PMID- 20806021
TI  - Response to clozapine in psychosis associated with velo-cardio-facial syndrome.

PMID- 20806022
TI  - Regarding catatonia.

PMID- 20806023
TI  - Regarding managing erotic and eroticized transference.

PMID- 20806024
TI  - Regarding psychiatric evaluations of asylum seekers.

PMID- 20806025
TI  - Hippocampal Neurogenesis: Can it be a Marker for New Antidepressants?

PMID- 20806026
TI  - Use of Antipsychotics Pre- and Post-Dissemination of CATIE Data.
AB  - We investigated the share of branded and generic antipsychotics before and after
      the publication of the CATIE results in September, 2005. According to our data,
      the publication of the CATIE results has had very little impact on new patient
      starts. To determine the impact of CATIE on use of olanzapine (Zyprexa((R)))
      subsequent to first line therapy, we also examined product share for switch/add
      patients. We found that since the publication of the CATIE results, the use of
      olanzapine has stabilized, following a decline subsequent to first line therapy,
      and may potentially be growing very slowly. An expert commentary is provided on
      the data.

PMID- 20806029
TI  - Identity theft in community mental health patients: two case reports.
AB  - Identity theft is a serious problem in the United States, and persons with
      enduring mental illnesses may be particularly vulnerable to becoming victims of
      this crime. Victims of identity theft experience a variety of consequences that
      include financial loss and serious emotional distress. Little is known about the
      impact of identity theft on individuals with mental illnesses. The two cases from
      a community mental health center presented in this article demonstrate many of
      the facets that may be associated with an increased risk for becoming the victim
      of identity theft. A summary of preventive steps as well as steps involved in
      resolving the crime once one has become a victim are presented.

PMID- 20806027
TI  - The management of suicidality: assessment and intervention.
AB  - A potentially suicidal patient is among the most difficult challenges faced by
      healthcare providers. This article reviews rates of suicide in America among the
      population as a whole and subpopulations based on age and race. In 2003, nearly
      11 Americans out of every 100,000 killed themselves. The rates of suicide were
      highest among whites, Native Americans, and elderly males. Suicide rates are
      elevated among many common mental illnesses, including major depression, bipolar
      disorder, schizophrenia, and alcoholism. Although statistical risk factors are
      significant, they are of limited help in determining what should be done with
      specific patients. Documenting demographic information, checking off diagnostic
      criteria, and asking patients if they have thoughts of killing themselves are
      only the start of the evaluation of suicidality. The complete assessment of
      suicidality requires inquiring into static and dynamic risks factors, warning
      signs and psychosocial stresses. Patients who report suicide plans should be
      asked about the plan in detail, including the chance of rescue, preparations for,
      and rehearsal of the suicide attempt. Interventions to reduce the risk of suicide
      should then be targeted towards eliminating or minimizing these various factors.
      Despite our best efforts patients will occasionally kill themselves. Studies have
      found that a majority of experienced psychiatrists have had a patient commit
      suicide. Following the suicide of a patient, clinicians will often experience a
      professional as well as personal response. Most providers who have experienced a
      patient suicide find talking to co-workers, peers, and friends to be useful.

PMID- 20806028
TI  - Social support and resilience to stress: from neurobiology to clinical practice.
AB  - Numerous studies indicate social support is essential for maintaining physical
      and psychological health. The harmful consequences of poor social support and the
      protective effects of good social support in mental illness have been well
      documented. Social support may moderate genetic and environmental vulnerabilities
      and confer resilience to stress, possibly via its effects on the hypothalamic
      pituitary-adrenocortical (HPA) system, the noradrenergic system, and central
      oxytocin pathways. There is a substantial need for additional research and
      development of specific interventions aiming to increase social support for
      psychiatrically ill and at-risk populations.

PMID- 20806030
TI  - Managing obsessive compulsive disorder: in children and adolescents.
AB  - Obsessive compulsive disorder (OCD) in children and adolescents is much the same
      as in adults with regard to symptoms and basic treatment modalities. There are
      some distinct considerations to note in the approach to treatment methods.
      Empirically supported treatments include both medications and cognitive
      behavioral therapy (CBT). It is important that psychotherapeutic treatment be
      tailored to the developmental level of the child. In this article, we will
      present, through case example, samples of varying the psychotherapeutic approach
      used for both child and adolescent cases of OCD. We will focus on exposure and
      response prevention techniques.

PMID- 20806031
TI  - Impact factor? Shmimpact factor!: the journal impact factor, modern day
      literature searching, and the publication process.
AB  - The journal impact factor is a measure of the citability of articles published in
      that journal-the more citations generated, the more important that article is
      considered to be, and as a consequence the prestige of the journal is enhanced.
      The impact factor is not without controversy, and it can be manipulated. It no
      longer dominates the choices of journals to search for information. Online search
      engines, such as PubMed, can locate articles of interest in seconds across
      journals regardless of high or low impact factors. Editors desiring to increase
      their influence will need to focus on a fast and friendly submission and review
      process, early online and speedy print publication, and encourage the rapid
      turnaround of high-quality peer reviews. Authors desiring to have their results
      known to the world have never had it so good-the internet permits anyone with
      computer access to find the author's work.

PMID- 20806032
TI  - Implementing performance improvement and measuring psychiatric care quality.

PMID- 20806033
TI  - A novel mitochondrial tRNA(Val) T1658C mutation identified in a CPEO family.
AB  - PURPOSE: To analyze mitochondrial DNA (mt DNA) gene mutations in a 19-year-old
      female patient, who presented with chronic progressive external ophthalmoplegia
      (CPEO), together with her mother and younger sister. METHODS: The diagnosis of
      mitochondrial myopathy was made based on clinical and biologic analysis.
      Histochemical methods were used to detect ragged-red fibers (RRFs) and ragged
      blue fibers (RBFs) on a muscle biopsy of the patient. All mitochondrial gene DNA
      fragments of the patient, her mother, and younger sister were amplified by
      polymerase chain reaction. The products were sequenced and compared with
      reference databases. RESULTS: A novel T1658C mutation and a known A10006G
      mutation were identified in the mitochondrial tRNA(Val) gene and the tRNA(Gly)
      gene, respectively, in the patient, her mother, and younger sister. The T1658C
      mutation changes the T loop structure of mitochondrial tRNA(Val) and the A10006G
      mutation disturbs the D loop of mitochondrial tRNA(Gly). CONCLUSIONS: The T1658C
      and A10006G mutations of mtDNA may be responsible for the pathogenesis of the
      patient with CPEO.

PMID- 20806034
TI  - The effects of rapamycin on lens epithelial cell proliferation, migration, and
      matrix formation: an in vitro study.
AB  - PURPOSE: The objective of the present study was to investigate the efficacy of
      rapamycin on rabbit lens epithelial cell proliferation, migration, and secretion
      of extracellular matrix fibronectin (Fn). METHODS: Rabbit lens epithelium cells
      (rLECs) were isolated from 1 month old rabbit. rLECs were either cultured for 24,
      48, or 72 h with different doses of rapamycin (0.1, 1, and 10 ng/ml). The
      proliferation kinetics, proliferating cell nuclear antigen (PCNA) expression, and
      basic fibroblast growth factor (bFGF)-induced migration of rLEC was determined by
      methyl thiazol tetrazolium (MTT) assay, western blotting and transwell chamber
      assay, respectively. The effect of rapamycin on the synthesis of Fn was examined
      via immunofluorescence. RESULTS: Rapamycin significantly inhibited rLEC
      proliferation and PCNA protein expression when administered doses and time
      periods except for 0.1 ng/ml for 24 h. bFGF-induced migration rLECs was inhibited
      by pretreatment with rapamycin for 48 h. Extracellular matrix Fn formation of
      rLECs was also reduced by rapamycin. CONCLUSIONS: In our study, rapamycin
      strongly inhibited rLEC proliferation, bFGF-induced migration, and extracellular
      matrix Fn formation. Thus, rapamycin may have a potential inhibition of posterior
      capsule opacification (PCO) and needs further study.

PMID- 20806035
TI  - Identification a novel MYOC gene mutation in a Chinese family with juvenile-onset
      open angle glaucoma.
AB  - PURPOSE: To describe the clinical and genetic findings in one Chinese family with
      juvenile-onset open angle glaucoma (JOAG). METHODS: One family was examined
      clinically and a follow-up took place 5 years later. After informed consent was
      obtained, genomic DNA was extracted from the venous blood of all participants.
      Linkage analysis was performed with three microsatellite markers around the MYOC
      gene (D1S196, D1S2815, and D1S218) in the family. Mutation screening of all
      coding exons of MYOC was performed by direct sequencing of PCR-amplified DNA
      fragments and restriction fragment length polymorphism (RFLP) analysis.
      Bioinformatics analysis by the Garnier-Osguthorpe-Robson (GOR) method predicted
      the effects of variants detected on secondary structures of the MYOC protein.
      RESULTS: Clinical examination and pedigree analysis revealed a three- generation
      family with seven members diagnosed with JOAG, three with ocular hypertension,
      and five normal individuals. Through genotyping, the pedigree showed a linkage to
      the MYOC on chromosome 1q24-25. Mutation screening of MYOC in this family
      revealed an A-->T transition at position 1348 (p. N450Y) of the cDNA sequence.
      This missense mutation co-segregated with the disease phenotype of the family,
      but was not found in 100 normal controls. Secondary structure prediction of the
      p.N450Y by the GOR method revealed the replacement of a coil with a beta sheet at
      the amino acid 447. CONCLUSIONS: Early onset JOAG, with incomplete penetrance, is
      consistent with a novel mutation in MYOC. The finding provides pre-symptomatic
      molecular diagnosis for the members of this family and is useful for further
      genetic consultation.

PMID- 20806036
TI  - Identification of a novel mutation in the NTF4 gene that causes primary open
      angle glaucoma in a Chinese population.
AB  - PURPOSE: Neurotrophin-4 protein (NT-4) plays a role in the protection of retinal
      ganglion cells by activating tyrosine kinase B (TrkB) receptors. A recent study
      identified mutations within the neurotrophin-4 (NTF4) gene to account for 1.7% of
      primary open-angle glaucoma (POAG) in Europeans. The aim of this study was to
      investigate the frequency of NTF4 mutations in Chinese POAG patients. METHODS:
      One hundred-seventy-four Chinese subjects with POAG and 91 normal Chinese
      subjects were recruited. POAG was defined by the presence of glaucomatous optic
      neuropathy, open angles on gonioscopy, and absence of secondary causes of
      glaucoma. The single coding exon of NTF4 was PCR amplified and subjected to
      bidirectional sequencing in all subjects. RESULTS: The mean age of POAG patients
      was 66.0+/-13.0 years (range 25-96 years) and that of controls was 67.1+/-4.6
      years (range 60-85 years). We identified a novel NTF4 missense mutation
      substituting leucine by serine at codon 113 (Leu113Ser) caused by a c.338T>C
      mutation in a single patient with unilateral POAG, who presented with a baseline
      intraocular pressure of 25 mmHg, a vertical cup-to-disc ratio of 0.9 and an
      inferior hemifield defect in the affected eye. Structural analysis indicated that
      the Leu113Ser mutation is likely to alter the NT-4 protein structure near the
      TrkB binding site and disrupts the formation of the NT-4-TrkB complex required
      for the activation of TrkB. CONCLUSIONS: Identification of a single mutation in
      our study suggests that NTF4 mutations are a rare cause of POAG (0.6%, 95%CI
      0.02%-3.16%) in Chinese people.

PMID- 20806037
TI  - Pharmacokinetic study of mangiferin in rat plasma and retina using high
      performance liquid chromatography.
AB  - PURPOSE: Although the naturally occurring antioxidant mangiferin has been widely
      used, it is not yet known whether it can cross the blood-retina barrier (BRB) and
      enter the eye. The purpose of this experiment was to investigate the ability of
      mangiferin to pass the blood-retina barrier. METHODS: Sprague-Dawley rats were
      used for biologic fluid sampling after intravenous administration of mangiferin
      at doses of 10, 25, and 50 mg/kg. Blood and retina samples were collected at
      different time points post-dose. High-performance liquid chromatography (HPLC)
      separation was conducted on a COSMOSIL 5C(18)-MS-II column (4.6 mm x 250 mm, 5
      microm) with a flow rate of 1.0 ml/min using a mobile phase comprised of methanol
      -2% glacial acetic acid (40:60 v:v). RESULTS: The HPLC method has proven suitable
      to determine the presence of mangiferin in the eye. The plasma concentration of
      mangiferin was dose dependent. Pharmacokinetic parameters of mangiferin in plasma
      after intravenous administration were fitted to the two-compartment model with
      the first-order elimination and first-order transfer between central and
      peripheral compartments. The concentration of mangiferin in the retina goes with
      that in the blood. Mangiferin concentrations in the retina reached 5.69+/-1.48
      microg/ml 0.5 h after intravenous administration (50 mg/kg) and then dropped
      gradually to 0.30+/-0.02 microg/ml 5.0 h later. The eye-to-plasma concentration
      ratio was 2.80%. CONCLUSIONS: Mangiferin can pass the blood-retina barrier after
      a single intravenous administration and may be a potential natural antioxidant in
      treating eye diseases.

PMID- 20806038
TI  - Gelatinous drop-like corneal dystrophy with a novel mutation of TACSTD2
      manifested in combination with spheroidal degeneration in a Chinese patient.
AB  - PURPOSE: To report the clinicopathological findings of a Chinese patient with an
      unusual phenotype of gelatinous drop-like corneal dystrophy (GDLD) combined with
      spheroidal degeneration and to detect molecular defect in the tumor-associated
      calcium signal transducer 2 (TACSTD2) gene. METHODS: Extensive physical and
      ophthalmologic examination of the patient was performed. Initially superficial
      keratectomy was performed for both eyes. Due to recurrence of the corneal
      opacity, penetrating keratoplasty for the right eye and deep lamellar
      keratoplasty for the left eye were performed. The obtained corneal tissues were
      examined by light microscopy. Molecular genetic analysis consisted of PCR
      amplification and direct automated sequencing of the complete coding region of
      TACSTD2. RESULTS: Slit-lamp biomicroscopy of the patient revealed bilateral band
      like corneal opacities composed of brown-yellow, oily appearing droplets at the
      first visit. Two years after superficial keratectomy, elevated mulberry-like
      gelatinous lesions companied with brown-yellow droplets in the superficial cornea
      in both eyes were found. Histological analysis of corneal tissue revealed
      subepithelial amorphous deposits stained positively with Congo red, typical of
      GDLD. Meanwhile, eosinophilic globular deposits with irregular peripheral margins
      and various sizes, which were characteristics of spheroidal degeneration, were
      found. Sequencing of TACSTD2 from the patient revealed a novel homozygous
      missense mutation c.354G>C, leading to amino acid substitution Q118H in the
      patient. CONCLUSIONS: This is the first report indicating a new type of
      gelatinous drop-like corneal dystrophy (GDLD) combined with spheroidal
      degeneration. Molecular analysis demonstrated a novel mutation in TACSTD2, which
      may expand the spectrum of mutations in TACSTD2.

PMID- 20806039
TI  - Assessment of heat shock protein (HSP60, HSP72, HSP90, and HSC70) expression in
      cultured limbal stem cells following air lifting.
AB  - OBJECTIVES: The aim of this study is to create an ex vivo model to examine the
      expression of major heat-shock protein (HSP) families; HSP60, HSP72, and HSP90,
      and heat-shock cognate 70 (HCS70) at the mRNA and protein level in
      differentiating corneal cells from limbal stem cells (LSC) following air
      exposure. METHODS: Limbal biopsies taken from cadaveric normal human limbus were
      cultivated as explants on human amniotic membrane (HAM) and plastic dish (PD).
      Corneal differentiation was induced by air lifting for 16 days. The expression of
      putative LSC markers (P63 and ATP-binding cassette G2 [ABCG2]), corneal markers
      (keratin 3 [K3/12] and connexin 43 [CX43]), and HSP60, HSP72, HSP90, and HSC70
      were tested by RT-PCR, immunofluorescence, and flow cytometry pre- and post-air
      exposure. Fresh limbal and corneal tissues were used as control groups. RESULTS:
      Air lifting induced corneal differentiation with a decrease in the number of
      P63(+) cells and an increase in the number of K3(+)/CX43(+) cells, which
      characterized transient amplifying cells (TACs). Moreover, denuded HAM provided a
      superior niche for LSC proliferation and phenotype maintenance in vitro.
      Additionally, we have evidence that expressions of HSC70 as well as HSP72 were
      enhanced through corneal differentiation and HSP90 post-air lifting in vitro and
      in vivo. HSP60, however, was not detected in either LSC or corneal cells, in vivo
      and in vitro. CONCLUSIONS: These results suggest that corneal differentiation
      following air exposure may regulate HSP72 and HSC70 expression. In addition,
      HSP72 and HSP90 may protect LSC and corneal cells against oxidative stress.

PMID- 20806040
TI  - High levels of retinal docosahexaenoic acid do not protect photoreceptor
      degeneration in VPP transgenic mice.
AB  - PURPOSE: To determine whether docosahexaenoic acid can protect against hereditary
      retinal degenerations in transgenic mice expressing the V20G, P23H, and P27L
      (VPP) rhodopsin mutations. METHODS: Female transgenic mice expressing the VPP
      rhodopsin mutation, known to cause a retinal degeneration, were bred to male
      transgenic mice expressing the fat-1 gene, which can convert n6 to n3
      polyunsaturated fatty acids (PUFA). Several weeks before breeding, the female
      mice were fed a standard diet containing 10% safflower oil (SFO), which is high
      in n6 and low in n3 PUFA (n6/n3=273). Offspring were genotyped and four groups
      identified: Fat1(+)/VPP(+), Fat1(-)/VPP(+), Fat1(+)/VPP(-), and Fat1(-)/VPP(-).
      Dams were maintained on the SFO diet during the nursing period and offspring were
      kept on the SFO diet after weaning. At 4, 16, and 28 weeks of age, retinal
      function was evaluated by electroretinography (ERG), photoreceptor cell loss was
      quantified by measuring outer nuclear layer thickness, and rhodopsin levels were
      determined. Fatty acid profiles were analyzed in whole retina, plasma, and liver
      at 4 and 28 weeks of age. RESULTS: Expression of fat-1 in the absence of dietary
      n3 PUFA led to the generation of two groups of mice with distinctly different
      levels of n3 and n6 PUFA in the three tissues that were analyzed. Already at four
      weeks of age, the retinas of fat-1 positive animals had higher levels of n3 PUFA
      than their wild-type counterparts (23%-29% versus 6.4%-6.5%). In addition, by
      four weeks of age, there was a significant loss of rod photoreceptor cells in the
      VPP mice. Progression of retinal degeneration occurred with increasing age in VPP
      positive mice, with photoreceptor cell death occurring in both inferior and
      superior regions. Amplitudes of the a- and b-waves of the ERG were significantly
      reduced with age, with VPP positive mice showing the greatest change. Rhodopsin
      content was lower in the VPP transgenic mice. There were no significant
      differences in outer nuclear layer thickness or ERG amplitudes between
      Fat1(+)/VPP(+) and Fat1(-)/VPP(+), or between Fat1(+)/VPP(-)and Fat1(-)/VPP(-)
      mice at any of the three ages. CONCLUSIONS: High levels of retinal
      docosahexaenoic acid do not protect mice expressing the VPP rhodopsin mutation
      from retinal degeneration.

PMID- 20806041
TI  - Advanced glycation end product (AGE) modified proteins in tears of diabetic
      patients.
AB  - PURPOSE: High glucose level in diabetic patients may lead to advanced glycation
      end product (AGE) modified proteins. This study investigated AGE modified
      proteins in tears and compared their levels in diabetic patients (DM) with non
      diabetic controls (CTL). METHODS: Basal tears were collected from DM with (DR) or
      without (DNR) retinopathy and CTL. Total AGE modified proteins were detected
      quantitatively by a dot immunobinding assay. The AGE modified proteins were
      separated in 1D- and 2D-SDS gels and detected by western-blotting. The individual
      AGE modified proteins were also compared between groups using densitometry.
      RESULTS: Compared with the CTL group, tear concentrations of AGE modified
      proteins were significantly elevated in DR and DNR groups. The concentration of
      AGE modified proteins in diabetic tears were positively correlated with AGE
      modified hemoglobin (HbA1c) and postprandial blood glucose level (PBG). Western
      blotting of AGE modified proteins from 1D-SDS gels showed several bands, the
      major one at around 60 kDa. The intensities of AGE modified protein bands were
      higher in DM tears than in CTL tears. Western blotting from 2D-SDS gels showed a
      strongly stained horizontal strip, which corresponded to the major band in 1D-SDS
      gels. Most of the other AGE modified protein species were within molecular weight
      of 30-60 kDa, PI 5.2-7.0. Densitometry analysis demonstrated several AGE modified
      proteins were elevated in DR or DNR tears. CONCLUSIONS: Total and some individual
      AGE modified proteins were elevated in DM tears. AGE modified proteins in tears
      may be used as biomarkers to diagnose diabetes and/or diabetic retinopathy.

PMID- 20806042
TI  - A novel mutation in GJA8 causing congenital cataract-microcornea syndrome in a
      Chinese pedigree.
AB  - PURPOSE: To identify the underlying genetic defect in a four-generation family of
      Chinese origin with autosomal dominant congenital cataract-microcornea syndrome
      (CCMC). METHODS: All individuals in the study underwent a full clinical
      examination and the details of history were collected . Genomic DNA extracted
      from peripheral blood was amplified by polymerase chain reaction (PCR) method and
      the exons of all candidate genes were sequenced. RESULTS: Direct sequencing of
      the encoding regions of the candidate genes revealed a heterozygous mutation
      c.592C-->T in exon 2 of the gap junction protein, alpha 8 (GJA8) gene. This
      mutation was responsible for the familial disorder through the substitution of a
      highly conserved arginine to tryptophan at codon 198 (p.R198W). This change co
      segregated with all affected members of the family, but was not detected either
      in the non-carrier relatives or in the 100 normal controls. CONCLUSIONS: This
      report is the first to relate p.R198W mutation in GJA8 with CCMC. The result
      expands the mutation spectrum of GJA8 in associated with congenital cataract and
      microcornea, and implies that this gene has direct involvement with the
      development of the lens as well as the other anterior segment of the eye.

PMID- 20806043
TI  - The expression of cytokines in the aqueous humor and serum during endotoxin
      induced uveitis in C3H/HeN mice.
AB  - PURPOSE: The cytokines present in the aqueous humor and serum of C3H/HeN mice
      with endotoxin-induced acute anterior uveitis were analyzed, and the potential
      role of the cytokines in the pathogenesis of the disease was investigated.
      METHODS: One hundred and eighty C3H/HeN mice were divided into an experimental
      group (n=150) and a control group (n=30). The mice in the experimental group were
      footpad-injected with 200 microg Vibro cholerae endotoxin (classical biotype,
      serotype Ogawa). The mice were then executed 4 h, 8 h, 16 h, 24 h, and 48 h after
      the injection of endotoxin. Aqueous humor and peripheral blood samples were
      collected using a microinjector. Ten samples were pooled together for analysis
      and centrifuged at 705x g, at 4 degrees C, for 3 min. The supernatant was
      collected and stored at -80 degrees C. The concentrations of tumor necrosis
      factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin
      10 (IL-10), and interferon-gamma (IFN-gamma) in the samples were measured using a
      Cytometric Bead Array (CBA). RESULTS: Acute anterior uveitis was successfully
      induced in C3H/HeN mice. At roughly 16 h post-injection, the concentrations of
      both IL-1 and IL-6 reached peak levels, and were significantly different from the
      control group (p=0.001 and p=0.001, respectively). At 24 h post-injection, the
      concentrations of IFN-gamma and IL-10 in the aqueous humor reached peak levels,
      and were significantly different from the control group (p=0.022 and p=0.003).
      The concentrations of IFN-gamma in serum at 4 and 24 hours were significantly
      different from the control group (p=0.033 and p=0.032). The concentration of IL
      10 in serum, at 24 h post-injection, was also found to be significantly different
      from the control group (p=0.003). The cytokine expression levels in the aqueous
      humor were consistent with what would be expected during the process of
      inflammation. CONCLUSIONS: Both IL-1 and IL-6 appear to play an important role in
      acute anterior uveitis; furthermore, the severity of inflammation may be
      associated with the dynamic balance of IFN-gamma and IL-10. Our results suggest
      that the cytokine network might be a useful therapeutic target in the treatment
      of acute anterior uveitis.

PMID- 20806044
TI  - R213W mutation in the retinoschisis 1 gene causes X-linked juvenile retinoschisis
      in a large Chinese family.
AB  - PURPOSE: We identified a large Chinese family with X-linked juvenile
      retinoschisis. The purpose of this study was to report the clinical findings of
      the family and to identify the genetic mutation by screening the retinoschisis 1
      (RS1) gene. METHODS: Family history was collected and all family members
      underwent routine ophthalmic examination. Venous blood was collected from family
      members and genomic DNA was extracted. The exons of RS1 were screened by PCR
      followed by direct sequencing and/or restriction enzyme digestion. RESULTS: The
      pedigree of interest was a four-generation family with 52 family members,
      including seven affected individuals. The proband was a 5-year-old boy showing
      highly elevated bullous retinoschisis with moderate vitreous hemorrhage in both
      eyes. Vitrectomy was performed in the left eye of the proband. Five affected
      males showed large peripheral retinoschisis in both eyes, either involving the
      macula or combined with foveal stellate cystic change. One of the affected family
      members showed only a foveal stellate cystic change in both eyes without
      periphery retinoschisis. Visual acuity of affected individuals ranged from hand
      motion to 0.4. The R213W mutation in exon 6 of RS1 was identified in all affected
      individuals, predicting an amino acid substitution of arginine to tryptophan at
      codon 213. CONCLUSIONS: Our data show that the R213W mutation in RS1 causes
      various severities of retinoschisis in a large Chinese family, providing further
      evidence for X-linked juvenile retinoschisis phenotypic variability.

PMID- 20806045
TI  - DUSP5 and DUSP6 modulate corneal epithelial cell proliferation.
AB  - PURPOSE: Dual specificity phosphatases (DUSPs) modulate the duration and
      magnitude of phospho-activation of Erk1/2, p38 and JNK1/2, the terminal kinases
      (TKs) of the mitogen activated protein kinase (MAPK) cascades. Three DUSPs,
      DUSP1, DUSP5, and DUSP6, are overexpressed in ocular surface side population stem
      cells (SPSCs). Our objective was to identify the impact of these enzymes on TK
      phosphorylation and proliferation of corneal epithelial cells. METHODS: SV40
      immortalized (sv) and expanded fresh human corneal epithelial cells (efHCECs)
      were transduced with lentivectors to elicit expression of shRNAmir against DUSP1,
      DUSP5, and JNK1 to thereby create the DUSP1i, DUSP5i and JNKi cell sublines, or
      overexpress DUSP6 (henceforth DUSP6(+)), respectively. TK phosphorylation status
      and proliferation rates were determined by immunoblotting and (3)H thymidine
      uptake. RESULTS: In both ef and svHCECs, EGF supplementation after a 24 h serum
      starvation caused a rapid 5-15 min spike in the phosphorylation of all three TK
      types. This was followed by gradual decreases to low phosphorylation levels
      within one h. These declines coincided with dramatic increases in DUSP1 and DUSP5
      protein expression. In DUSP1i, the DUSP1 increase was abolished. All 3 TKs
      maintained high phosphorylation levels for at least 90 min and proliferation
      rates were unchanged from non-transduced cells. In DUSP5i, the DUSP5 protein
      increase was prevented, the post peak phosphorylation decrease occurred only on
      Erk1/2 and the proliferation rate increased by 50%-60%. In JNK1i, JNK1 was
      essentially knocked out and proliferation rates were also markedly elevated. At
      steady-state, DUSP1i maintained high levels of pJNK1/2 expression. In DUSP6(+)
      Erk1/2 phosphorylation was prevented and proliferation rates decreased to less
      than 50%. CONCLUSIONS: DUSP5 and DUSP6 selectively control ERK pathway activity
      and proliferation. The lack of an effect of DUSP1 knockdown on proliferation can
      be attributed to its pan-MAPK effect. The expected augmented proliferative
      response due to enhanced and prolonged phosphorylation of Erk1/2 following DUSP1
      knockdown does not occur because a pJNK1/2 antiproliferative effect is
      simultaneously unleashed.

PMID- 20806046
TI  - Different phenotypes of lattice corneal dystrophy type I in patients with 417C>T
      (R124C) and 1762A>G (H572R) mutations in TGFBI (BIGH3).
AB  - PURPOSE: To describe clinical data and to characterize mutations in the
      transforming growth factor beta-induced (TGFBI) gene in patients from three
      unrelated Chilean families with lattice corneal dystrophy type I (LCDI). METHODS:
      Snellen acuity tests, anterior segment slit lamp examinations, dilated fundus
      evaluations, and tonometry were performed for seven patients--five females and
      two males belonging to three unrelated families--affected with lattice corneal
      dystrophy Type I. Genomic DNA was also extracted from peripheral leukocytes from
      the seven patients and four healthy relatives. The 417C>T mutation (R124C) was
      screened using PCR-RFLP for the seven patients and four healthy relatives. Exons
      11, 12, 13, and 14 were sequenced in one patient not carrying the mutation in
      codon 124. Comparison of phenotype to genotype was performed. RESULTS: The seven
      patients studied exhibited LCDI in both eyes, most of which were symmetric.
      Affected individuals demonstrated progression from central subepithelial
      needlelike deposits and polymorphic anterior stromal opacities. The age at onset
      of symptoms varied between six to 15 years old in Family One; the patient in
      Family Two was five years old and the patient in Family Three was 21 years old.
      Visual acuity varied from 1.0 to 0.05. Two patients, aged 50 and 45 years,
      underwent penetrating keratoplasty in both eyes, and two patients, aged 47 and 24
      years, underwent penetrating keratoplasty in one eye. The only patient in Family
      Three exhibited a somewhat distinct phenotype, with yellowish discoloration in
      the anterior stroma and fewer, but thicker lattice lines than the patients in
      Families One and Two. Screening for the mutation C>T at the nucleotide position
      417 (R124C) in exon 4 in the three families revealed the heterozygous R124C
      mutation in Families One and Two. In Family Two, the mutation was a de novo
      mutation, as neither parent was a carrier. Screening by sequencing analysis for
      mutation in exons 11, 12, 13, and 14 in the affected patient in Family Three
      revealed a heterozygous A1762G mutation (H572R) in exon 13. CONCLUSIONS: This is
      the second report of the 417C>T mutation and the first report of 1762 A>G
      mutation (H572R) in Chilean patients. The H572R mutation identified is associated
      with a distinct lattice corneal dystrophy type I phenotype.

PMID- 20806047
TI  - Identification of dominant FOXE3 and PAX6 mutations in patients with congenital
      cataract and aniridia.
AB  - PURPOSE: Aniridia and congenital cataract represent rare but severe developmental
      ocular conditions. We examined 33 probands from France for mutations in several
      transcription factors associated with these phenotypes, the forkhead box E3
      (FOXE3), paired box gene 6 (PAX6), paired-like homeodomain transcription factor 2
      (PITX2), and paired-like homeodomain transcription factor 3 (PITX3) genes.
      METHODS: Out of 33 probands, 27 were affected with congenital cataract while the
      remaining six were affected with aniridia (with or without cataract). The coding
      regions of FOXE3, PAX6, PITX2, and PITX3 were examined by direct DNA sequencing
      of gene-specific PCR products. RESULTS: A novel dominant mutation at the stop
      codon of FOXE3, c.959G>C (p.X320SerextX72), was identified in a patient with
      congenital cataract. Another novel FOXE3 sequence change, c.571-579dup
      (p.Tyr191_Pro193dup), was identified in a patient with aniridia, mild lens
      opacities, and some additional ocular defects; this patient was also found to
      carry a nonsense mutation in PAX6. PAX6 mutations were identified in two
      additional probands with aniridia and cataracts. None of the observed sequence
      alterations were found in normal controls. No mutations were identified in PITX2
      or PITX3. CONCLUSIONS: The p.X320SerextX72 mutation is only the fourth FOXE3
      allele associated with a dominant phenotype since the majority of FOXE3 mutations
      appear to be recessive with no phenotype observed in heterozygous carriers. The
      encoded protein is predicted to contain a complete normal sequence followed by
      seventy-two erroneous amino acids; the position and effect of this mutation are
      similar to two of the previously reported dominant changes, suggesting a common
      mechanism for dominant alleles. The p.Tyr191_Pro193dup is predicted to result in
      an in-frame duplication of three amino acids; however, the contribution of this
      mutation to the phenotype is unclear since the affected patient also carries a
      nonsense mutation in PAX6 which acts upstream of FOXE3 in the molecular pathway.
      The identified PAX6 mutations correspond to the two most commonly observed mutant
      alleles and demonstrate phenotypes that are consistent with the previously
      reported spectrum.

PMID- 20806048
TI  - Spatial and temporal dissociation of AQP4 and Kir4.1 expression during induction
      of refractive errors.
AB  - PURPOSE: Spatial co-localization of aquaporin water channels (AQP4) and inwardly
      rectifying potassium ion channels (Kir4.1) on the endfeet regions of glial cells
      has been suggested as the basis of functionally interrelated mechanisms of
      osmoregulation in brain edema. The aim of this study was to investigate the
      spatial and temporal changes in the expression of AQP4 and Kir4.1 channels in an
      avascular retina during the first week of the optical induction of refractive
      errors. METHODS: Three-day-old hatchling chicks were randomly assigned to three
      groups and either did not wear lenses or were monocularly goggled with +/-10D
      lenses for varying times up to 7 days before biometric assessment. Retinal tissue
      was prepared either for western blot analysis to show the presence of the AQP4
      and Kir4.1 protein in the chick retina or for immunolocalization using AQP4 and
      Kir4.1 antibodies to determine the regional distribution and intensity of
      labeling during the induction of refractive errors. RESULTS: As expected,
      ultrasonography demonstrated that all eyes showed rapid elongation post hatching.
      Negative lens-wearing eyes elongated faster than fellow eyes or normal non
      goggled eyes and became progressively more myopic with time post lensing.
      Positive lens-wearing eyes showed reduced ocular growth compared to normal
      controls and developed a hyperopic refraction. Quantitative immunohistochemistry
      revealed the upregulation of AQP4 channel expression on Muller cells in the
      retinal nerve fiber layer during the first 2 days of negative lens wear. Kir4.1
      channel upregulation in the inner plexiform layer was only found on day 4 of
      positive lens wear during the development of refractive hyperopia. CONCLUSIONS:
      These results indicate that the expression of AQP4 and Kir4.1 channels on Muller
      cells is associated with the changes in ocular volume seen during the induction
      of refractive errors. However, the sites of greatest expression and the temporal
      pattern of the upregulation of AQP4 and Kir4.1 were dissimilar, indicating a
      dissociation of AQP4 and Kir4.1 function during refractive error development.
      Increased AQP4 expression in the nerve fiber layer is suggested to contribute to
      the rapid axial elongation and movement of fluid into the vitreous cavity in the
      presence of minus lenses; whereas, upregulation of Kir4.1 channels appears to
      play a role in limiting axial elongation in the presence of plus lenses.

PMID- 20806049
TI  - Isolation of adult progenitor cells with neuronal potential from rabbit corneal
      epithelial cells in serum- and feeder layer-free culture conditions.
AB  - PURPOSE: To isolate progenitor cells from rabbit corneal epithelial cells (CEC)
      in serum- and feeder layer-free culture conditions and to compare the self
      renewal capacity of corneal epithelial progenitor cells obtained from the central
      and limbal regions of the cornea. METHODS: Tissue samples of New Zealand white
      rabbit corneas were dissected from the limbal and central regions to obtain CEC
      for sphere-forming culture, in which the cells formed spheres in serum-free
      medium containing growth factors. The number of primary and secondary sphere
      colonies and the size of the primary spheres were compared between the limbal and
      central regions. To promote differentiation, isolated sphere colonies were plated
      in dishes coated with poly-L-lysine (PLL)/laminin. The expression of epithelial,
      neural, and mesenchymal mRNAs was examined in the sphere colonies and their
      progeny by immunocytochemistry and/or the reverse transcription-polymerase chain
      reaction (RT-PCR). Adherent differentiated cells from the sphere colonies were
      also examined morphologically. RESULTS: Primary spheres were isolated from both
      the limbal and central regions of the cornea. The rate of primary sphere
      formation by CEC from the limbal region (55.6+/-10.6/10,000 cells) was
      significantly higher than that by cells from the central cornea (43.1+/
      7.2/10,000 cells, p=0.0028), but there was no significant difference in the size
      of primary spheres derived from both regions. The self-renewal capacity of cells
      from the limbal region was higher than that of cells from the central region, as
      evidenced by the significantly higher secondary sphere formation rate of limbal
      cells (38.7+/-8.5/10,000 cells) in comparison with that for central cells (31.3+/
      5.7/10,000 cells, p=0.013). The primary sphere colonies expressed
      bromodeoxyuridine (BrdU), a 63-kDa protein (p63), p75 neurotrophin receptor
      (p75(NTR)), and nestin, whereas their progeny expressed cytokeratin 3,
      cytokeratin 12, vimentin, alpha-smooth muscle actin, microtubule-associated
      protein 2, and neuron-specific enolase on immunocytochemical analysis. These
      markers were confirmed by RT-PCR. CONCLUSIONS: Our findings indicate that limbal
      CEC contain more progenitor cells with a stronger self-renewal capacity than
      cells from the central region. These progenitor cells differentiate into the
      epithelial lineage, and can also produce neuronal protein.

PMID- 20806050
TI  - A novel mutation in retinitis pigmentosa GTPase regulator gene with a distinctive
      retinitis pigmentosa phenotype in a Chinese family.
AB  - PURPOSE: To screen the mutation in the retinitis pigmentosa GTPase regulator
      (RPGR) ORF15 in a large Chinese family with X-linked recessive retinitis
      pigmentosa and describe the phenotype in affected male and female carriers.
      METHODS: Ophthalmic examination was performed on 77 family members to identify
      affected individuals and to characterize the disease phenotype. PCR and direct
      sequencing were used for screening mutations in the RPGR gene. RESULTS: Mutation
      screening demonstrated a novel mutation ORF15+577_578 delAG, which caused an open
      reading frameshift and resulted in premature truncation of the RPGR protein. The
      mutation was detected in eight affected male individuals and 14 obligate female
      carriers of the family and was found to segregate with the phenotype in this
      family. The mutation led to a severe retinitis pigmentosa (RP) phenotype in male
      affected individuals, with some variability in the age of onset of night
      blindness and visual acuity, but was recessive in female carriers without an RP
      phenotype. However, the state associated with the carrier was moderate to high
      myopia with the refractive error ranging from -5.00 D to 22.00 D in 14 female
      carriers. CONCLUSIONS: This novel mutation in RPGR ORF15 causes a serious RP
      phenotype in males and no RP phenotype in female carriers. Moderate to high
      myopia was a particular feature for female carriers in this pedigree. Our finding
      expands the spectrum of RPGR mutations causing X-linked RP and expands phenotypic
      spectrum of the disease in a Chinese family. This finding will be useful for
      further genetic consultations and genetic diagnosis.

PMID- 20806051
TI  - Corrigendum to Solvent-dependent oxidative coupling of 1-aryl-1,3-dicarbonyls and
      styrene.
AB  - This report describes the scope and mechanism of the solvent-dependent,
      chemoselective oxidative coupling of 1-aryl-1,3-dicarbonyls with styrene using
      Ce(IV) reagents. Dihydrofuran derivatives are obtained when reactions are
      performed in methanol whereas nitrate esters can be selectively synthesized in
      acetonitrile and methylene chloride. Mechanistic studies are consistent with the
      rate of solvent-assisted deprotonation of a radical cation intermediate playing
      an integral role in the selective formation of products.

PMID- 20806052
TI  - Insights into neurogenesis and aging: potential therapy for degenerative disease?
AB  - Neurogenesis is the process by which new neural cells are generated from a small
      population of multipotent stem cells in the adult CNS. This natural generation of
      new cells is limited in its regenerative capabilities and also declines with age.
      The use of stem cells in the treatment of neurodegenerative disease may hold
      great potential; however, the age-related incidence of many CNS diseases
      coincides with reduced neurogenesis. This review concisely summarizes current
      knowledge related to adult neurogenesis and its alteration with aging and
      examines the feasibility of using stem cell and gene therapies to combat diseases
      of the CNS with advancing age.

PMID- 20806053
TI  - Mapping neuropeptide expression by mass spectrometry in single dissected
      identified neurons from the dorsal ganglion of the nematode Ascaris suum.
AB  - We have developed a method for dissecting single neurons from the nematode
      Ascaris suum, in order to determine their peptide content by mass spectrometry
      (MS). In this paper, we use MALDI-TOF MS and tandem MS to enumerate and sequence
      the peptides present in the two neurons, ALA and RID, that comprise the dorsal
      ganglion. We compare the peptide content determined by MS with the results of
      immunocytochemistry and in situ hybridization of previously isolated peptides
      AF2, AF8 and 6 peptides encoded by the afp-1 transcript. We find complete
      agreement between the three techniques, which validates single neuron MS as a
      method for peptide localization. We also discovered and sequenced 6 novel
      peptides in the ALA neuron. Cloning of cDNAs and database searching of Genomic
      Survey Sequences showed that transcript afp-12 encodes peptide AF36
      (VPSAADMMIRFamide), and afp-13 encodes AF19 (AEGLSSPLIRFamide), AF34
      (DSKLMDPLIRFamide), AF35 (DPQQRIVTDETVLRFamide), and 3 non-amidated peptides
      (PepTT, PepTL, and PepGE). We have found no similarities with reported peptide
      expression in the nematode Caenorhabditis elegans. This method promises to be
      ideally suited for determining the peptide content of each of the 298 neurons in
      the nervous system of this nematode.

PMID- 20806054
TI  - APAP and Alternative Titration Methods.
AB  - PURPOSE OF REVIEW: Positive airway pressure therapy (PAP) is commonly prescribed
      treatment for obstructive sleep apnea (OSA). Traditionally, the determination of
      the optimal pressure for treatment of sleep-disordered breathing was made by
      manual titration of the device by a sleep technician in attendance during
      polysomnography. However, the advent of alternative methods for determination of
      optimal PAP - such as auto-titrating PAP (APAP) - has seen tremendous growth over
      the past decade. The purpose of this review is to improve our understanding of
      the currently available alternative methods for titration of PAP in patients with
      sleep-disordered breathing (SDB) with special emphasis on obstructive sleep
      apnea.  RECENT FINDINGS: Recent prospective-randomized studies of alternative
      methods of titration suggest that pressure determinations made by such devices
      are comparable to traditional manual titrations made in the sleep laboratory.
      Obstacles to the adoption of such alternative modes of titration into day-to-day
      practice may be attributable to issues surrounding appropriate patient selection,
      differences between devices, re-imbursement policies of third party payors,
      consensus amongst sleep experts, and individual physicians' practice patterns and
      volumes. While newer generations and types of auto-titrating PAP devices are
      entering the sleep field constantly, providers' knowledge and time availability
      remain limiting factors.  SUMMARY: There is tremendous growth in the technology
      and scientific evidence in support of alternative modes of PAP titration for
      sleep-disordered breathing, but barriers to implementation remain.

PMID- 20806055
TI  - Welfare Gains from Financial Liberalization.
AB  - Financial liberalization has been a controversial issue, as empirical evidence
      for growth enhancing effects is mixed. Here, we find sizable welfare gains from
      liberalization (cost to repression), though the gain in economic growth is
      ambiguous. We take the view that financial liberalization is a government policy
      that alters the path of financial deepening, while financial deepening is
      endogenously chosen by agents given a policy and occurs in transition towards a
      distant steady state. This history-dependent view necessitates the use of
      simulation analysis based on a growth model. Our application is a specific
      episode: Thailand from 1976 to 1996.

PMID- 20806056
TI  - Data Fusion for Improved Respiration Rate Estimation.
AB  - We present an application of a modified Kalman-Filter (KF) framework for data
      fusion to the estimation of respiratory rate from multiple physiological sources
      which is robust to background noise. A novel index of the underlying signal
      quality of respiratory signals is presented and then used to modify the noise
      covariance matrix of the KF which discounts the effect of noisy data. The signal
      quality index, together with the KF innovation sequence, is also used to weight
      multiple independent estimates of the respiratory rate from independent KFs. The
      approach is evaluated on both a realistic artificial ECG model (with real
      additive noise), and on real data taken from 30 subjects with overnight
      polysomnograms, containing ECG, respiration and peripheral tonometry waveforms
      from which respiration rates were estimated. Results indicate that our automated
      voting system can out-perform any individual respiration rate estimation
      technique at all levels of noise and respiration rates exhibited in our data. We
      also demonstrate that even the addition of a noisier extra signal leads to an
      improved estimate using our framework. Moreover, our simulations demonstrate that
      different ECG respiration extraction techniques have different error profiles
      with respect to the respiration rate, and therefore a respiration rate-related
      modification of any fusion algorithm may be appropriate.

PMID- 20806057
TI  - Temperature and current coefficients of lasing wavelength in tunable diode laser
      spectroscopy.
AB  - The factors determining temperature and current coefficients of lasing wavelength
      are investigated and discussed under monitoring CO(2)-gas absorption spectra. The
      diffusion rate of Joule heating at the active layer to the surrounding region is
      observed by monitoring the change in the junction voltage, which is a function of
      temperature and the wavelength (frequency) deviation under sinusoidal current
      modulation. Based on the experimental results, the time interval of monitoring
      the wavelength after changing the ambient temperature or injected current
      (scanning rate) has to be constant at least to eliminate the monitoring error
      induced by the deviation of lasing wavelength, though the temperature and current
      coefficients of lasing wavelength differ with the rate.

PMID- 20806058
TI  - Impact on the Spatial Resolution Performance of a Monolithic Crystal PET Detector
      Due to Different Sensor Parameters.
AB  - The performance characteristics of a monolithic crystal PET detector utilizing a
      novel sensor on the entrance surface (SES) design is reported. To facilitate this
      design, we propose to utilize a 2D silicon photomultiplier (SiPM) array device.
      SiPMs are a form of Geiger-Muller mode avalanche photodiodes (GMAPD) that can
      provide signal gain similar to a photomultiplier tube (PMT). Since these devices
      are still under active development, their performance parameters are changing.
      Using a multi-step simulation process, we investigated how different SiPM
      parameters affect the performance of a monolithic crystal PET detector. These
      parameters include gain variability between different channels; gain instability;
      and dark count noise. The detector simulated was a 49.6 mm by 49.6 mm by 15 mm
      LYSO crystal detector readout by a 16 by 16 array of 2.8 mm by 2.8 mm SiPM
      elements. To reduce the number of signal channels that need to be collected, the
      detector utilizes row-column summing. A statistics based positioning method is
      used for event positioning and depth of interaction (DOI) decoding. Of the
      variables investigated, the dark count noise had the largest impact on the
      intrinsic spatial resolution. Gain differences of 5-10% between detector
      calibration and detector testing had a modest impact on the intrinsic spatial
      resolution performance and led to a slight bias in positioning. There was no
      measurable difference with a gain variability of up to 25% between the individual
      SiPM channels. Based upon these results we are planning to cool our detectors
      below room temperature to reduce dark count noise and to actively control the
      temperature of the SiPMs to reduce drifts in gain over time.

PMID- 20806059
TI  - Ezrin is highly expressed in early thymocytes, but dispensable for T cell
      development in mice.
AB  - BACKGROUND: Ezrin/radixin/moesin (ERM) proteins are highly homologous proteins
      that function to link cargo molecules to the actin cytoskeleton. Ezrin and moesin
      are both expressed in mature lymphocytes, where they play overlapping roles in
      cell signaling and polarity, but their role in lymphoid development has not been
      explored. METHODOLOGY/PRINCIPAL FINDINGS: We characterized ERM protein expression
      in lymphoid tissues and analyzed the requirement for ezrin expression in lymphoid
      development. In wildtype mice, we found that most cells in the spleen and thymus
      express both ezrin and moesin, but little radixin. ERM protein expression in the
      thymus was differentially regulated, such that ezrin expression was highest in
      immature thymocytes and diminished during T cell development. In contrast, moesin
      expression was low in early thymocytes and upregulated during T cell development.
      Mice bearing a germline deletion of ezrin exhibited profound defects in the size
      and cellularity of the spleen and thymus, abnormal thymic architecture,
      diminished hematopoiesis, and increased proportions of granulocytic precursors.
      Further analysis using fetal liver chimeras and thymic transplants showed that
      ezrin expression is dispensable in hematopoietic and stromal lineages, and that
      most of the defects in lymphoid development in ezrin(-/-) mice likely arise as a
      consequence of nutritional stress. CONCLUSIONS/SIGNIFICANCE: We conclude that
      despite high expression in lymphoid precursor cells, ezrin is dispensable for
      lymphoid development, most likely due to redundancy with moesin.

PMID- 20806060
TI  - Influence of perineurial cells and Toll-like receptors 2 and 9 on Herpes simplex
      type 1 entry to the central nervous system in rat encephalitis.
AB  - Herpes simplex encephalitis (HSE) is a rare disease with high mortality and
      significant morbidity among survivors. We have previously shown that
      susceptibility to HSE was host-strain dependent, as severe, lethal HSE developed
      after injection of human Herpes simplex type 1 virus (HSV-1) into the whiskers
      area of DA rats, whereas PVG rats remained completely asymptomatic. In the
      present study we investigated the early immunokinetics in these strains to
      address the underlying molecular mechanisms for the observed difference. The
      virus distribution and the immunological responses were compared in the whiskers
      area, trigeminal ganglia and brain stem after 12 hours and the first four days
      following infection using immunohistochemistry and qRT-PCR. A conspicuous
      immunopathological finding was a strain-dependent difference in the spread of the
      HSV-1 virus to the trigeminal ganglia, only seen in DA rats already from 12 hpi.
      In the whiskers area infected perineurial cells were abundant in the susceptible
      DA strain after 2 dpi, whereas in the resistant PVG rats HSV-1 spread was
      confined only to the epineurium. In both strains activation of Iba1(+)/ED1(+)
      phagocytic cells followed the distribution pattern of HSV-1 staining, which was
      visible already at 12 hours after infection. Notably, in PVG rats higher mRNA
      expression of Toll-like receptors (Tlr) -2 and -9, together with increased
      staining for Iba1/ED1 was detected in the whiskers area. In contrast, all other
      Tlr-pathway markers were expressed at higher levels in the susceptible DA rats.
      Our data demonstrate the novel observation that genetically encoded properties of
      the host nerve and perineurial cells, recruitment of phagocyting cells together
      with the low expression of Tlr2 and -9 in the periphery define the susceptibility
      to HSV-1 entry into the nervous system.

PMID- 20806061
TI  - PeakRegressor identifies composite sequence motifs responsible for STAT1 binding
      sites and their potential rSNPs.
AB  - How to identify true transcription factor binding sites on the basis of sequence
      motif information (e.g., motif pattern, location, combination, etc.) is an
      important question in bioinformatics. We present "PeakRegressor," a system that
      identifies binding motifs by combining DNA-sequence data and ChIP-Seq data.
      PeakRegressor uses L1-norm log linear regression in order to predict peak values
      from binding motif candidates. Our approach successfully predicts the peak values
      of STAT1 and RNA Polymerase II with correlation coefficients as high as 0.65 and
      0.66, respectively. Using PeakRegressor, we could identify composite motifs for
      STAT1, as well as potential regulatory SNPs (rSNPs) involved in the regulation of
      transcription levels of neighboring genes. In addition, we show that among five
      regression methods, L1-norm log linear regression achieves the best performance
      with respect to binding motif identification, biological interpretability and
      computational efficiency.

PMID- 20806062
TI  - Differences in the cognitive skills of bonobos and chimpanzees.
AB  - While bonobos and chimpanzees are both genetically and behaviorally very similar,
      they also differ in significant ways. Bonobos are more cautious and socially
      tolerant while chimpanzees are more dependent on extractive foraging, which
      requires tools. The similarities suggest the two species should be cognitively
      similar while the behavioral differences predict where the two species should
      differ cognitively. We compared both species on a wide range of cognitive
      problems testing their understanding of the physical and social world. Bonobos
      were more skilled at solving tasks related to theory of mind or an understanding
      of social causality, while chimpanzees were more skilled at tasks requiring the
      use of tools and an understanding of physical causality. These species
      differences support the role of ecological and socio-ecological pressures in
      shaping cognitive skills over relatively short periods of evolutionary time.

PMID- 20806063
TI  - TDP-43-mediated neuron loss in vivo requires RNA-binding activity.
AB  - Alteration and/or mutations of the ribonucleoprotein TDP-43 have been firmly
      linked to human neurodegenerative diseases, including amyotrophic lateral
      sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). The relative
      impacts of TDP-43 alteration, mutation, or inherent protein function on neural
      integrity, however, remain less clear--a situation confounded by conflicting
      reports based on transient and/or random-insertion transgenic expression. We
      therefore performed a stringent comparative investigation of impacts of these TDP
      43 modifications on neural integrity in vivo. To achieve this, we systematically
      screened ALS/FTLD-associated and synthetic TDP-43 isoforms via same-site gene
      insertion and neural expression in Drosophila; followed by transposon-based motor
      neuron-specific transgenesis in a chick vertebrate system. Using this bi-systemic
      approach we uncovered a requirement of inherent TDP-43 RNA-binding function--but
      not ALS/FTLD-linked mutation, mislocalization, or truncation--for TDP-43-mediated
      neurotoxicity in vivo.

PMID- 20806064
TI  - Human neural stem cells differentiate and promote locomotor recovery in an early
      chronic spinal cord injury NOD-scid mouse model.
AB  - BACKGROUND: Traumatic spinal cord injury (SCI) results in partial or complete
      paralysis and is characterized by a loss of neurons and oligodendrocytes, axonal
      injury, and demyelination/dysmyelination of spared axons. Approximately 1,250,000
      individuals have chronic SCI in the U.S.; therefore treatment in the chronic
      stages is highly clinically relevant. Human neural stem cells (hCNS-SCns) were
      prospectively isolated based on fluorescence-activated cell sorting for a
      CD133(+) and CD24(-/lo) population from fetal brain, grown as neurospheres, and
      lineage restricted to generate neurons, oligodendrocytes and astrocytes. hCNS
      SCns have recently been transplanted sub-acutely following spinal cord injury and
      found to promote improved locomotor recovery. We tested the ability of hCNS-SCns
      transplanted 30 days post SCI to survive, differentiate, migrate, and promote
      improved locomotor recovery. METHODS AND FINDINGS: hCNS-SCns were transplanted
      into immunodeficient NOD-scid mice 30 days post spinal cord contusion injury.
      hCNS-SCns transplanted mice demonstrated significantly improved locomotor
      recovery compared to vehicle controls using open field locomotor testing and
      CatWalk gait analysis. Transplanted hCNS-SCns exhibited long-term engraftment,
      migration, limited proliferation, and differentiation predominantly to
      oligodendrocytes and neurons. Astrocytic differentiation was rare and mice did
      not exhibit mechanical allodynia. Furthermore, differentiated hCNS-SCns
      integrated with the host as demonstrated by co-localization of human cytoplasm
      with discrete staining for the paranodal marker contactin-associated protein.
      CONCLUSIONS: The results suggest that hCNS-SCns are capable of surviving,
      differentiating, and promoting improved locomotor recovery when transplanted into
      an early chronic injury microenvironment. These data suggest that hCNS-SCns
      transplantation has efficacy in an early chronic SCI setting and thus expands the
      "window of opportunity" for intervention.

PMID- 20806065
TI  - Host genetic factors and vaccine-induced immunity to HBV infection: haplotype
      analysis.
AB  - Hepatitis B virus (HBV) infection remains a significant health burden world-wide,
      although vaccines help decrease this problem. We previously identified
      associations of single nucleotide polymorphisms in several candidate genes with
      vaccine-induced peak antibody level (anti-HBs), which is predictive of long-term
      vaccine efficacy and protection against infection and persistent carriage; here
      we report on a haplotype-based analysis. A total of 688 SNPs from 117 genes were
      examined for a two, three and four sliding window haplotype analysis in a Gambian
      cohort. Analysis was performed on 197 unrelated individuals, 454 individuals from
      174 families, and the combined sample (N = 651). Global and individual haplotype
      association tests were carried out (adjusted for covariates), employing peak anti
      HBs level as outcome. Five genes (CD44, CD58, CDC42, IL19 and IL1R1) had at least
      one significant haplotype in the unrelated or family analysis as well as the
      combined analysis. Previous single locus results were confirmed for CD44
      (combined global p = 9.1x10(-5) for rs353644-rs353630-rs7937602) and CD58
      (combined global p = 0.008 for rs1414275-rs11588376-rs1016140). Haplotypes in
      CDC42, IL19 and IL1R1 also associated with peak anti-HBs level. We have
      identified strong haplotype effects on HBV vaccine-induced antibody level in five
      genes, three of which, CDC42, IL19 and IL1R1, did not show evidence of
      association in a single SNP analyses and corroborated the majority of these
      effects in two datasets. The haplotype analysis identified associations with HBV
      vaccine-induced immunity in several new genes.

PMID- 20806071
TI  - Fine-needle aspiration cytology of extra mammary metastatic lesions in the
      breast: A retrospective study of 36 cases diagnosed during 18 years.
AB  - BACKGROUND: Metastatic tumors in the breast require treatment according to origin
      and type of tumor. It is important to recognize these lesions in fine-needle
      aspiration cytology (FNAC) in order to avoid unnecessary mastectomy or non
      relevant chemotherapy. The aim of this study was to evaluate the cytological
      features of metastatic tumors and possible criteria that could alert us as to the
      possibility of a metastasis from an extra mammary malignancy. METHODS: The
      material included 36 confirmed or suspected metastases in the breast registered
      in the pathology files at Oslo University Hospital, Ulleval, during 1990-2007.
      There were a total of 6,325 cases of malignant breast FNAC, representing 30 men
      and 6,295 women. Smears were evaluated for the amount of material, presence or
      absence of myoepithelial cells, microcalcifications, mitoses and necrotic
      material. All carcinomas were graded. RESULTS: There were seven men (7/30 =
      23.3%) and 29 women (29/6,295 = 0.46%). The primary tumor was known in 22 cases
      (22/36 = 61.1%). No other primary tumor was known and metastatic lesion was not
      initially suspected in 14 cases (14/36 = 38.9%). The most common origin was lung
      (15/36 = 41.7%). In five cases (5/36 = 13.9%), the origin remained uncertain.
      CONCLUSIONS: Metastases from extra mammary sites are (relatively) common in males
      (23.3%). In women, metastatic lesions are rare (0.46%). A large proportion of
      them (88%) are high-grade adenocarcinomas and poorly differentiated carcinomas
      that may resemble grade 3 ductal carcinomas. Unusual clinical and/or radiological
      presentation in combination with high-grade malignant cells should alert us to
      consider the possibility of a metastasis.

PMID- 20806072
TI  - Fine needle aspiration diagnosis of Rosai-Dorfman disease in an osteolytic lesion
      of bone.
AB  - Sinus histiocytosis with massive lymphadenopathy (SHML) or Rosai-Dorfman disease
      (RDD) is an uncommon but well-defined benign self-limited clinicopathological
      entity. It mainly involves lymph nodes. Extranodal involvement is seen in up to
      43% of cases, with the most common location in the head and neck region. Primary
      RDD occurring in the bone is rare with only twelve cases reported in the
      literature to date, all diagnosed on histology except one by fine needle
      aspiration (FNA) cytology. We report a case of RDD diagnosed by FNA cytology in a
      28 year-old female presented as an osteolytic lesion of superior pubic ramus
      where the differential diagnosis included a sarcoma and lymphoma. Based on the
      cytologic findings, a diagnosis of a RDD was considered during the rapid FNA on
      site with no clinical history provided. The diagnosis of RDD was further
      confirmed by immunohistochemical stains and histology diagnosis. Our findings
      show that even in the absence of a clinical history, FNA is a less invasive and a
      very reliable tool for the diagnosis of SHML (RDD).

PMID- 20806066
TI  - Tissue-specific and ubiquitous expression patterns from alternative promoters of
      human genes.
AB  - BACKGROUND: Transcriptome diversity provides the key to cellular identity. One
      important contribution to expression diversity is the use of alternative
      promoters, which creates mRNA isoforms by expanding the choice of transcription
      initiation sites of a gene. The proximity of the basal promoter to the
      transcription initiation site enables prediction of a promoter's location based
      on the gene annotations. We show that annotation of alternative promoters
      regulating expression of transcripts with distinct first exons enables a novel
      methodology to quantify expression levels and tissue specificity of mRNA
      isoforms. PRINCIPAL FINDINGS: The use of distinct alternative first exons in
      3,296 genes was examined using exon-microarray data from 11 human tissues.
      Comparing two transcripts from each gene we found that the activity of
      alternative promoters (i.e., P1 and P2) was not correlated through tissue
      specificity or level of expression. Furthermore neither P1 nor P2 conferred any
      bias for tissue-specific or ubiquitous expression. Genes associated with specific
      diseases produced transcripts whose limited expression patterns were consistent
      with the tissue affected in disease. Notably, genes that were historically
      designated as tissue-specific or housekeeping had alternative isoforms that
      showed differential expression. Furthermore, only a small number of alternative
      promoters showed expression exclusive to a single tissue indicating that "tissue
      preference" provides a better description of promoter activity than tissue
      specificity. When compared to gene expression data in public databases, as few as
      22% of the genes had detailed information for more than one isoform, whereas the
      remainder collapsed the expression patterns from individual transcripts into one
      profile. CONCLUSIONS: We describe a computational pipeline that uses microarray
      data to assess the level of expression and breadth of tissue profiles for
      transcripts with distinct first exons regulated by alternative promoters. We
      conclude that alternative promoters provide individualized regulation that is
      confirmed through expression levels, tissue preference and chromatin
      modifications. Although the selective use of alternative promoters often goes
      uncharacterized in gene expression analyses, transcripts produced in this manner
      make unique contributions to the cell that requires further exploration.

PMID- 20806073
TI  - APTIMA assay on SurePath liquid-based cervical samples compared to endocervical
      swab samples facilitated by a real time database.
AB  - BACKGROUND: Liquid-based cytology (LBC) cervical samples are increasingly being
      used to test for pathogens, including: HPV, Chlamydia trachomatis (CT) and
      Neisseria gonorrhoeae (GC) using nucleic acid amplification tests. Several
      reports have shown the accuracy of such testing on ThinPrep (TP) LBC samples.
      Fewer studies have evaluated SurePath (SP) LBC samples, which utilize a different
      specimen preservative. This study was undertaken to assess the performance of the
      Aptima Combo 2 Assay (AC2) for CT and GC on SP versus endocervical swab samples
      in our laboratory. MATERIALS AND METHODS: The live pathology database of
      Montefiore Medical Center was searched for patients with AC2 endocervical swab
      specimens and SP Paps taken the same day. SP samples from CT-and/or GC-positive
      endocervical swab patients and randomly selected negative patients were studied.
      In each case, 1.5 ml of the residual SP vial sample, which was in SP preservative
      and stored at room temperature, was transferred within seven days of collection
      to APTIMA specimen transfer tubes without any sample or patient identifiers.
      Blind testing with the AC2 assay was performed on the Tigris DTS System (Gen
      probe, San Diego, CA). Finalized SP results were compared with the previously
      reported endocervical swab results for the entire group and separately for
      patients 25 years and younger and patients over 25 years. RESULTS: SP specimens
      from 300 patients were tested. This included 181 swab CT-positive, 12 swab GC
      positive, 7 CT and GC positive and 100 randomly selected swab CT and GC negative
      patients. Using the endocervical swab results as the patient's infection status,
      AC2 assay of the SP samples showed: CT sensitivity 89.3%, CT specificity 100.0%;
      GC sensitivity and specificity 100.0%. CT sensitivity for patients 25 years or
      younger was 93.1%, versus 80.7% for patients over 25 years, a statistically
      significant difference (P = 0.02). CONCLUSIONS: Our results show that AC2 assay
      of 1.5 ml SP samples transferred to APTIMA specimen transfer medium within seven
      days is sufficiently sensitive and specific to be used to screen for CT and GC.
      CT sensitivity may be somewhat reduced in samples from patients over 25 years. SP
      specimens retained in the original SP fixative for longer time intervals also may
      have decreased sensitivity, due to deterioration of RNA, but this was not
      assessed in this study. The ability to tap the live pathology database is a
      valuable tool that can useful to conduct clinical studies without a costly
      prospective clinical trial.

PMID- 20806074
TI  - Nutrient density of beverages in relation to climate impact.
AB  - The food chain contributes to a substantial part of greenhouse gas (GHG)
      emissions and growing evidence points to the urgent need to reduce GHGs emissions
      worldwide. Among suggestions were proposals to alter food consumption patterns by
      replacing animal foods with more plant-based foods. However, the nutritional
      dimensions of changing consumption patterns to lower GHG emissions still remains
      relatively unexplored. This study is the first to estimate the composite nutrient
      density, expressed as percentage of Nordic Nutrition Recommendations (NNR) for 21
      essential nutrients, in relation to cost in GHG emissions of the production from
      a life cycle perspective, expressed in grams of CO(2)-equivalents, using an index
      called the Nutrient Density to Climate Impact (NDCI) index. The NDCI index was
      calculated for milk, soft drink, orange juice, beer, wine, bottled carbonated
      water, soy drink, and oat drink. Due to low-nutrient density, the NDCI index was
      0 for carbonated water, soft drink, and beer and below 0.1 for red wine and oat
      drink. The NDCI index was similar for orange juice (0.28) and soy drink (0.25).
      Due to a very high-nutrient density, the NDCI index for milk was substantially
      higher (0.54) than for the other beverages. Future discussion on how changes in
      food consumption patterns might help avert climate change need to take both GHG
      emission and nutrient density of foods and beverages into account.

PMID- 20806075
TI  - Spectrum of candidate gene mutations associated with Indian familial
      oculocutaneous and ocular albinism.
AB  - PURPOSE: Albinism is a group of genetic disorders, showing a broad spectrum of
      different phenotypes. The purpose of this study was to screen known candidate
      genes for oculocutaneous albinism (OCA) and ocular albinism (OA) mutations in
      Indian patients. METHODS: Blood samples were collected from 23 probands and 13
      affected family members from 23 genetically unrelated Indian families (22
      diagnosed as OCA and 1 diagnosed as OA) and analyzed by bidirectional DNA
      sequencing of the classic OCA genes--tyrosinase (TYR, or oculocutaneous albinism
      IA), pink eyed dilution (P; or oculocutaneous albinism II (OCA2]), tyrosinase
      related protein 1 (TYRP1), solute carrier family 45, member 2 (SLC45A2; or
      membrane-associated transporter protein [MATP])--and the OA1 gene, G protein
      coupled receptor 143 (GPR143). RESULTS: Three missense mutations, c. 715 C>T
      (R239W), c. 896 G>A (R299H), c.1255 G>A (G419R), and one termination c. 832 C>T
      (R278X), were identified in TYR, as well as one novel mutation, c.1453 G>A
      (G485R) in P. One novel single nucleotide polymorphism (SNP) was identified in
      both TYR and P; few reported SNPs were identified. The G>A base substitution
      caused relatively conservative amino acid changes, which altered glycine to
      arginine residues within the topological domain. The novel OCA2 mutation was not
      present in 100 control samples. This study identified two probands carrying
      mutations alone, 16 probands carrying SNPs alone, 4 probands carrying both
      mutations and SNPs and only one proband carrying neither mutations nor SNPs.
      CONCLUSIONS: Although sequence analysis was performed with all five candidate
      genes, only four (17.39%) of the 23 probands showed mutations in TYR and 2
      probands (8.69%) showed an unreported novel mutation in P. Genetic counseling for
      phenotypical diagnosis and genetic mutation screening of these genes will help to
      minimize the incidence of OCA and OA in future generations.

PMID- 20806076
TI  - Antiglycating potential of Zingiber officinalis and delay of diabetic cataract in
      rats.
AB  - PURPOSE: Advanced glycation end products (AGE) are associated in the development
      of several pathophysiologies including diabetic cataract. Earlier we have
      reported that some common dietary agents have antiglycating activity and ginger
      (Zingiber officinalis) was one of the few prominent agents that effectively
      prevented AGE formation in vitro. In this study we investigated the potential of
      ginger to prevent diabetic cataract in rats. METHODS: Diabetes was induced in
      Wistar-NIN rats by intraperitoneal injection of streptozotocin (35 mg/kg
      bodyweight) and the control rats received vehicle alone. While a set of diabetic
      animals received AIN-93 diet, another set received either 0.5 or 3% ginger in
      their diet for a period of two months. Cataract progression was monitored by slit
      lamp biomicroscope. At the end of two months, the animals were sacrificed to
      evaluate non-enzymatic glycation and osmotic stress in the eye lens. RESULTS:
      Slit-lamp examination revealed that feeding of ginger not only delayed the onset
      but also the progression of cataract in rats. Molecular analyses indicated that
      feeding of ginger significantly inhibited the formation of various AGE products
      including carboxymethyl lysine in the eye lens. In addition, ginger also
      countered hyperglycemia-induced osmotic stress in the lens. CONCLUSIONS: The
      results indicated that ginger was effective against the development of diabetic
      cataract in rats mainly through its antiglycating potential and to a lesser
      extent by inhibition of the polyol pathway. Thus, ingredients of dietary sources,
      such as ginger, may be explored for the prevention or delay of diabetic
      complications.

PMID- 20806077
TI  - Effect of down-regulation of aquaporins in human corneal endothelial and
      epithelial cell lines.
AB  - PURPOSE: The purpose of this study was to determine the effects of down
      regulation of Aquaporin 1 (AQP1) and Aquaporin 5 (AQP5) on cell proliferation and
      migration in human corneal endothelial (HCEC) and human corneal epithelial
      (CEPI17) cell lines, respectively. METHODS: AQP1 and AQP5 were down regulated
      using siRNA following lipofectamine-mediated transfection in corneal endothelial
      and epithelial cells, respectively. Down-regulation was confirmed using RT-PCR,
      indirect immunofluorescence, and immunoblot analysis. Total internal reflection
      fluorescence (TIRF) microscopy was used to detect cell surface aquaporin
      expression. Cell proliferation was determined by SRB (sulfrodamine B) assay. Cell
      migration was determined by in vitro wound healing and migration assay. RESULTS:
      In HCEC cells, AQP1 was localized to the cytosol as well as cell membrane and its
      down-regulation resulted in decreased cell proliferation and migration with a
      significant decrease in phosphorylated ERK (pERK). In CEPI17 cells AQP5 protein
      expression was also localized to cytosol as well as cell membrane. AQP5 down
      regulation resulted in an increase in proliferation and cell migration with no
      significant difference in pERK. CONCLUSIONS: AQP1 plays a role in HCEC
      proliferation and migration via the ERK signaling pathway and therefore may have
      significant implications in corneal endothelial dysfunction whereas; AQP5 may
      play an indirect role in human corneal epithelial cell proliferation and
      migration.

PMID- 20806078
TI  - An ADAM9 mutation in canine cone-rod dystrophy 3 establishes homology with human
      cone-rod dystrophy 9.
AB  - PURPOSE: To identify the causative mutation in a canine cone-rod dystrophy (crd3)
      that segregates as an adult onset disorder in the Glen of Imaal Terrier breed of
      dog. METHODS: Glen of Imaal Terriers were ascertained for crd3 phenotype by
      clinical ophthalmoscopic examination, and in selected cases by
      electroretinography. Blood samples from affected cases and non-affected controls
      were collected and used, after DNA extraction, to undertake a genome-wide
      association study using Affymetrix Version 2 Canine single nucleotide
      polymorphism chips and 250K Sty Assay protocol. Positional candidate gene
      analysis was undertaken for genes identified within the peak-association signal
      region. Retinal morphology of selected crd3-affected dogs was evaluated by light
      and electron microscopy. RESULTS: A peak association signal exceeding genome-wide
      significance was identified on canine chromosome 16. Evaluation of genes in this
      region suggested A Disintegrin And Metalloprotease domain, family member 9
      (ADAM9), identified concurrently elsewhere as the cause of human cone-rod
      dystrophy 9 (CORD9), as a strong positional candidate for canine crd3. Sequence
      analysis identified a large genomic deletion (over 20 kb) that removed exons 15
      and 16 from the ADAM9 transcript, introduced a premature stop, and would remove
      critical domains from the encoded protein. Light and electron microscopy
      established that, as in ADAM9 knockout mice, the primary lesion in crd3 appears
      to be a failure of the apical microvilli of the retinal pigment epithelium to
      appropriately invest photoreceptor outer segments. By electroretinography,
      retinal function appears normal in very young crd3-affected dogs, but by 15
      months of age, cone dysfunction is present. Subsequently, both rod and cone
      function degenerate. CONCLUSIONS: Identification of this ADAM9 deletion in crd3
      affected dogs establishes this canine disease as orthologous to CORD9 in humans,
      and offers opportunities for further characterization of the disease process, and
      potential for genetic therapeutic intervention.

PMID- 20806079
TI  - MicroRNA expression in human retinal pigment epithelial (ARPE-19) cells:
      increased expression of microRNA-9 by N-(4-hydroxyphenyl)retinamide.
AB  - PURPOSE: MicroRNAs (miRNAs) are important regulators of many cellular functions
      due to their ability to target mRNAs for degradation or translational inhibition.
      Previous studies have reported that the expression of microRNA-9 (miR-9) is
      regulated by retinoic acid and reactive oxygen species (ROS). We have previously
      shown that N-(4-hydroxyphenyl)-retinamide (4HPR), a retinoic acid derivative,
      induces ROS generation and apoptosis in cultured human retinal pigment epithelial
      (RPE) cells, known as ARPE-19 cells. The aim of the present study was to
      investigate the expression of miR-9 in ARPE-19 cells in response to 4HPR
      treatment, and to identify other miRNAs normally expressed in these cells.
      METHODS: ARPE-19 cells in culture were treated with 4HPR, the total RNA fractions
      were isolated, and the expression of various miRNAs and mRNAs was analyzed using
      real-time PCR. The miRNA expression profile of ARPE-19 cells was analyzed using
      microarray hybridization. RESULTS: Treatment of ARPE-19 cells with 4HPR resulted
      in apoptosis characterized by the increased expression of HMOX1 and GADD153
      genes. A twofold increase in the expression of miR-9 was also observed during
      this response. Potential binding sites for the transcription factors encoded by
      CEBPA and CEBPB genes were found to be present in the putative promoter regions
      of all three genes encoding miR-9. 4HPR-induced miR-9 expression was associated
      with parallel increases in the expression of these transcription factor genes. 5
      Aza-2'-deoxycytidine, a methyl transferase inhibitor, also increased the
      expression of miR-9 in ARPE-19 cells. Microarray hybridization analysis
      identified let-7b, let-7a, miR-125b, miR-24, miR-320, miR-23b, let-7e, and let-7d
      as the most abundant miRNAs normally expressed in ARPE-19 cells. These miRNAs are
      known to regulate cell growth, differentiation or development. The 4HPR treatment
      increased the expression of miR-16, miR-26b, miR-23a, and miR-15b in ARPE-19
      cells, although these increases were modest when compared to the increase in the
      expression of miR-9. CONCLUSIONS: Our studies demonstrate that miR-9 is expressed
      in the RPE cell line ARPE-19, and its expression is increased by a retinoic acid
      derivative and by an inhibitor of promoter hypermethylation. Several miRNAs with
      inherent ability to regulate cell growth, differentiation and development are
      also normally expressed in ARPE-19 cells. Thus, miR-9 and other miRNAs could be
      important in maintaining RPE cell function.

PMID- 20806080
TI  - Cannabidiol protects retinal neurons by preserving glutamine synthetase activity
      in diabetes.
AB  - PURPOSE: We have previously shown that non-psychotropic cannabidiol (CBD)
      protects retinal neurons in diabetic rats by inhibiting reactive oxygen species
      and blocking tyrosine nitration. Tyrosine nitration may inhibit glutamine
      synthetase (GS), causing glutamate accumulation and leading to further neuronal
      cell death. We propose to test the hypothesis that diabetes-induced glutamate
      accumulation in the retina is associated with tyrosine nitration of GS and that
      CBD treatment inhibits this process. METHODS: Sprague Dawley rats were made
      diabetic by streptozotocin injection and received either vehicle or CBD (10
      mg/kg/2 days). After eight weeks, retinal cell death, Muller cell activation, GS
      tyrosine nitration, and GS activity were determined. RESULTS: Diabetes causes
      significant increases in retinal oxidative and nitrative stress compared with
      controls. These effects were associated with Muller cell activation and
      dysfunction as well as with impaired GS activity and tyrosine nitration of GS.
      Cannabidiol treatment reversed these effects. Retinal neuronal death was
      indicated by numerous terminal deoxynucleotidyl transferase dUTP nick end
      labeling (TUNEL)-labeled cells in diabetic rats compared with untreated controls
      or CBD-treated rats. CONCLUSIONS: These results suggest that diabetes-induced
      tyrosine nitration impairs GS activity and that CBD preserves GS activity and
      retinal neurons by blocking tyrosine nitration.

PMID- 20806081
TI  - X-ray induced cataract is preceded by LEC loss, and coincident with accumulation
      of cortical DNA, and ROS; similarities with age-related cataracts.
AB  - PURPOSE: To compare age-related cataractous (ARC) changes in unirradiated mice
      lenses to those induced by head-only X-irradiation of 3 month-old mice. METHODS:
      lens epithelial cells (LECs) as well as partially degraded cortical DNA were
      visualized in fixed sections using 4',6-diamidino-2-phenylindole (DAPI) staining,
      and in fresh lenses using the vital stain Hoechst 33342. reactive oxygen species
      (ROS) activity was also visualized directly in fresh lenses using the vital dye
      Dihydrorhodamine (DHR). In fixed lenses an antibody specific for 8-OH Guanosine
      (8-OH-G) lesions was used to visualize DNA oxidative adducts from ROS damage.
      Alpha smooth muscle actin was visualized using specific antibodies to determine
      if myofibroblasts were present. Fluorescence was quantified using Laser Scanning
      Confocal Microscopy (LSCM). The degree of lens opacity and cataract formation was
      determined by slit lamp, or from digitalized images of light reflections taken
      with a low magnification light microscope. RESULTS: Using DNA- and ROS-specific
      vital fluorescent dyes, and laser scanning confocal microscopy we have previously
      described 4 changes in the aging rodent lenses: 1) a significantly decreased
      density of surface LECs in lenses from old compared to younger mice and rats; 2)
      a very large increase in retained cortical nuclei and DNA fragments in the
      secondary lens fibers of old rodent lenses; 3) increased cortical ROS in old
      rodent lenses; 4) increased cataract concomitantly with the cortical DNA and ROS
      increases. In the current study we report that these same 4 changes also occur in
      an accelerated fashion in mice given head-only X-irradiation at 3 months of age.
      In addition to vital staining of fresh lenses, we also examined sections from
      fixed eyes stained with DAPI or hematoxylin and eosin (H&E) and found the same
      loss of surface LECs and accumulation of undigested nuclei and debris in
      secondary lens fibers occur with age or following X-irradiation. In addition
      sections from fixed-eyes were examined for ROS damage to DNA with antibodies
      specific for 8-OH-G lesions. The frequency of 8-OH-G lesions increased
      dramatically in lenses from old unirradiated mice over 24 months of age, and
      similarly in X-irradiated lenses by 9-11 months post irradiation. The
      accumulation of cortical nuclei was not the result of conversion or invasion by
      myofibroblasts as tested by antibodies to a marker for such cells, alpha smooth
      muscle actin. CONCLUSIONS: X-irradiation damage induces a large decrease in
      surface LECs over a period of 3-11 months post X-irradiation of young mice. These
      changes are similar in extent to those seen in 24-29 months-old control mouse
      lenses with age-related cataracts. In 24+ month-old unirradiated mice the
      secondary lens fibers are not able to degrade nuclei or nuclear DNA efficiently
      and accumulate large numbers of cortical nuclei and nuclear fragments as well as
      ROS and 8-OHG lesions. X-irradiated lenses develop the same abnormalities in a
      more accelerated fashion. The extensive loss of LECS and accumulation of
      undegraded nuclei, ROS, and ROS damage may play a causal role in cataract
      generation in both unirradiated old mice and in previously irradiated young adult
      mice.

PMID- 20806082
TI  - Abnormal fiber end migration in Royal College of Surgeons rats during posterior
      subcapsular cataract formation.
AB  - PURPOSE: Prior structural studies of posterior subcapsular cataract (PSC)
      development in Royal College of Surgeons (RCS) rats suggest that migration of
      basal fiber ends was disrupted, ultimately resulting in a PSC. Therefore the goal
      of this study was to assess the overall migration patterns as well as changes to
      the structure and cytoskeleton of basal fiber ends during PSC development.
      METHODS: Lenses from 48 RCS dystrophic rats (RCS/Lav) and 24 genetically matched
      control animals (RCS-rdy(+)/Lav) from 2 to 8 weeks old were examined. Equatorial
      diameters were measured and suture patterns were photographed immediately
      following enucleation/dissection. Right eye lenses were fixed and processed to
      visualize the actin cytoskeleton via laser scanning confocal microscopy (LSCM),
      left eye lenses were decapsulated, fixed and processed for scanning electron
      microscopy (SEM). Scaled 3D-computer assisted drawings (CADs) and animations were
      constructed from the data to depict the changes in suture patterns and fiber end
      architecture. RESULTS: At 2 weeks, dystrophic lenses displayed an inverted Y
      suture on the posterior, and by 3 weeks most lenses had at least one sub-branch.
      Additional sub-branches were observed with time, opacities being visible as early
      as 4 weeks and progressing into PSC plaques by 6 weeks. Control lenses displayed
      inverted Y sutures at all ages and were transparent. SEM of dystrophic lenses
      revealed fiber ends with normal size, shape, arrangement, and filopodia at 2
      weeks; scattered areas of dome-shaped fiber ends and small filopodia were present
      at 3 weeks. At 4 weeks the irregularly arranged domed fiber ends had extremely
      long filopodia with 'boutons' at their tips. By 6 weeks all fiber ends within
      plaques displayed rounded or domed basal membranes and lacked filopodial
      extensions. Control lenses at all time points had comparable ultrastructure to
      the 2 week old dystrophic lenses. F-actin arrangement within the basal membrane
      complex (BMC) of control lenses showed the expected peripheral pattern of
      labeling at all ages. Dystrophic RCS lenses at 2 weeks were comparable to
      controls, however by 3-4 weeks they displayed scattered foci of F-actin within
      the BMC. At all time points thereafter, F-actin was rearranged into a 'rosette'
      pattern of prominent foci at cell vertices. CONCLUSIONS: The data are consistent
      with the hypothesis that migration of basal fiber ends is altered in a two stage
      process wherein initially, migration patterns undergo a rapid shift resulting in
      abnormal suture sub-branch formation. Subsequent cytological alterations are
      consistent with an eventual cessation of migration, precluding proper targeting
      of basal ends to their sutural destinations and leading to cataract plaque
      formation.

PMID- 20806084
TI  - Dairy products and plasma cholesterol levels.
AB  - Cholesterol synthesized in the body or ingested is an essential lipid component
      for human survival from our earliest life. Newborns ingest about 3-4 times the
      amount per body weight through mother's milk compared to the dietary intake of
      adults. A birth level of 1.7 mmol/L plasma total cholesterol will increase to 4
      4.5 mmol/L during the nursing period and continue to increase from adulthood
      around 40% throughout life. Coronary artery disease and other metabolic disorders
      are strongly associated with low-density lipoprotein (LDL) and high-density
      lipoprotein (HDL) cholesterol as well as triacylglycerol concentration. Milk fat
      contains a broad range of fatty acids and some have a negative impact on the
      cholesterol rich lipoproteins. The saturated fatty acids (SFAs), such as palmitic
      acid (C16:0), myristic acid (C14:0), and lauric acid (C12:0), increase total
      plasma cholesterol, especially LDL, and constitute 11.3 g/L of bovine milk, which
      is 44.8% of total fatty acid in milk fat. Replacement of dairy SFA and trans
      fatty acids with polyunsaturated fatty acids decreases plasma cholesterol,
      especially LDL cholesterol, and is associated with a reduced risk of
      cardiovascular disease. Available data shows different effects on lipoproteins
      for different dairy products and there is uncertainty as to the impact a
      reasonable intake amount of dairy items has on cardiovascular risk. The aim of
      this review is to elucidate the effect of milk components and dairy products on
      total cholesterol, LDL, HDL, and the LDL/HDL quotients. Based on eight recent
      randomized control trials of parallel or cross-over design and recent reviews it
      can be concluded that replacement of saturated fat mainly (but not exclusively)
      derived from high-fat dairy products with low-fat dairy products lowers LDL/HDL
      cholesterol and total/HDL cholesterol ratios. Whey, dairy fractions enriched in
      polar lipids, and techniques such as fermentation, or fortification of cows
      feeding can be used to produce dairy products with more beneficial effects on
      plasma lipid profile.

PMID- 20806085
TI  - Case study documenting the diagnosis of idiopathic CD4+ Lymphocytopenia in a
      patient with atypical fungal infection (disseminated blastomycosis) by FNA of
      adrenal mass.
AB  - Idiopathic CD4+ lymphocytopenia, described in 1992 by the Centers for Disease
      Control, is characterized by persistent CD4+ lymphocytopenia (less than 300 cells
      per micro-liter) in nonimmunosuppressed, HIV negative individuals, who present
      with atypical infections. This rare though likely undiagnosed entity is
      associated with chronic disseminated forms of either fungal or bacterial
      infections in otherwise healthy adults. We report a case of a 59-year-old male
      with ring-enhancing brain lesions, bilateral adrenal masses, lung and vocal cord
      nodules, where the diagnosis of exclusion was metastatic malignancy. Fine needle
      aspiration (FNA) of the adrenal mass and a subsequent vocal cord biopsy confirmed
      chronic widely disseminated blastomycosis. Flow cytometric evaluation of
      peripheral blood documented persistent selective CD4+ lymphocytopenia with T8
      (suppressor) T-Lymphocyte count within normal range. We believe that idiopathic
      CD4+ lymphocytopenia is an important etiologic factor to be considered for
      patients who present with mass lesions and are diagnosed by FNA with atypical
      fungal infections. We relate the diagnostic criteria for idiopathic CD4+
      lymphocytopenia and the importance of providing on-site triage for FNA samples
      for fungal studies and correlation for flow cytometry.

PMID- 20806083
TI  - Resveratrol protects human lens epithelial cells against H2O2-induced oxidative
      stress by increasing catalase, SOD-1, and HO-1 expression.
AB  - PURPOSE: Oxidative damage induced by H(2)O(2) treatment can irreversibly damage
      the lens epithelium, resulting in cell death and cataract. Whether the effects of
      oxidative stress could be attenuated in cultured human lens epithelial cells by
      incubation with resveratrol (RES) is still unknown. In the present study, we
      examined the function of resveratrol in protecting human lens epithelial B-3
      (HLEB-3) cells against H(2)O(2) induced cell death and cell apoptosis, its role
      in reducing H(2)O(2) induced intracellular reactive oxygen species (ROS)
      accumulation, and investigated the mechanism by which resveratrol underlies the
      effect. METHODS: HLEB-3 cells, a human lens epithelial cell line, were exposed to
      100 muM H(2)O(2) with or without RES pre-treatment at different concentrations
      for different time duration. Cell viabilities were monitored by 4-[3-[4
      iodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio-1,3-benzene disulfonate] (WST-1)
      assay. The apoptosis rate and ROS generation were detected by flow cytometric
      analysis. Expression levels of superoxide dismutases-1 (SOD-1), catalase, and
      heme oxygenase-1 (HO-1) proteins were measured by western-blotting analysis. p38
      and c-jun N terminal kinase (JNK) activation was also evaluated by western
      blotting analysis. RESULTS: Resveratrol clearly reduced H(2)O(2) induced cell
      apoptosis and ROS accumulation; protected HLEB-3 cells from H(2)O(2) induced
      oxidative damage, and increased the expression levels of SOD-1, catalase, and HO
      1. Further studies showed that RES also inhibited H(2)O(2) induced p38 and JNK
      phosphorylation. CONCLUSIONS: These findings suggested that RES protected HLEB-3
      cells from H(2)O(2) induced oxidative damage, presumably by inducing three
      antioxidative enzymes including catalase, SOD-1, and HO-1.

PMID- 20806086
TI  - Evaluation of atypical squamous cells on conventional cytology smears: An
      experience from a screening program practiced in limited resource settings.
AB  - BACKGROUND: The Bethesda system (TBS) 2001 has subdivided the category of
      atypical squamous cells (ASC) into: ASC-US (undetermined significance) and ASC-H
      (cannot exclude high-grade squamous intraepithelial lesion (HSIL)). The present
      study is an analysis of ASC-US and ASC-H cases diagnosed in a screening program
      practiced in limited resource settings. METHODS: During the period January 2005
      to December 2008, a total of 9190 smears were received, of which 568 were
      unsatisfactory. Cases initially diagnosed as ASC-US (n=74) and ASC-H (n=29) on
      conventional cytology smears were reviewed. Biopsy and human papilloma virus
      (HPV) results were available in limited cases. RESULTS: On review, diagnosis of
      ASC-US was retained in 49 (66.2%) of the 74 initially diagnosed ASC-US cases.
      Remaining 12 cases were re-labeled as negative for intraepithelial lesion or
      malignancy (NILM), nine as low-grade squamous intraepithelial lesion (LSIL),
      three as ASC-H and one case as squamous carcinoma (SCC). Similarly, on review,
      diagnosis of ASC-H cases was retained in 17 of the 29 initially diagnosed ASC-H
      cases. Seven cases were re-labeled as NILM, three as HSIL and one case each as
      ASC-US and SCC. Overall, 8622 cases (96.6%) were diagnosed as NILM, 72 (0.83%) as
      LSIL, 121 (1.40%) as HSIL, 23 (0.26%) as SCC, 50 (0.57%) as ASC-US cases, 20
      (0.23%) as ASC-H, five (0.05%) as atypical glandular cells (AGC) and two cases as
      adenocarcinomas. Out of 50 ASC-US cases, biopsy in 23 cases showed presence of
      CIN 1 in 16 cases (69.5%) and CIN 2 in one case (4.34%), while the remaining six
      cases were negative for CIN/malignancy. The remaining 20 cases with unavailable
      biopsy results were HPV-positive. Out of 20 ASC-H cases, biopsy in 15 revealed
      CIN 2 and above in 11 cases (73.3%). Three cases (20%) revealed CIN 1.
      CONCLUSIONS: Critical review is helpful in further reducing the number of ASC
      cases. The percentage of cases with CIN 2 and above is higher with ASC-H cases.
      The reason for relative increase in HSILs in the present study included referral
      bias in the screening program.

PMID- 20806087
TI  - Colposcopic evaluation of cervix with persistent inflammatory Pap smear: A
      prospective analytical study.
AB  - BACKGROUND: Inflammatory Pap smear is the most common report received by a
      gynecologist. The cervical screening algorithm for benign cellular changes on the
      Pap smear recommends treatment of infection if indicated and a repeat Pap smear
      in 4 to 6 months time. If the inflammatory changes still persist, subject the
      patient to colposcopy. However, in practice, this is not followed, especially in
      developing countries like ours where proper screening protocols are not
      available. Hence, a good number of patients in the premalignant stage are being
      missed. This study was undertaken to evaluate patients with persistent
      inflammatory Pap smears without atypia using colposcopy. METHODS: A prospective
      analytical study of 150 gynecologial patients with persistent inflammatory Pap
      smear between 2006 and 2008 in an out-patient setting. All of them were subjected
      to colposcopy and biopsy from the abnormal areas. The incidence of cervical
      intraepithelial neoplasia (CIN)/invasive carcinoma was calculated by
      proportions/percentages. RESULTS: The incidence of invasive carcinoma was <1%.
      But, the incidence of pre-malignant lesions (CIN) was high (20.9%). CIN 2/3 and
      carcinoma in situ were present in 6.9% of the cases. CONCLUSIONS: Patients with
      persistent inflammatory Pap smears can harbour a high proportion of CIN and hence
      these patients will need further evaluation.

PMID- 20806088
TI  - Pituitary carcinoma diagnosed on fine needle aspiration: Report of a case and
      review of pathogenesis.
AB  - Pituitary carcinoma (PC) is a very rare entity (0.2% of all pituitary tumors),
      with only about 140 cases reported in English literature. There are no reliable
      histological, immunohistochemical or ultrastructural features distinguishing
      pituitary adenoma (PA) from PC. By definition, a diagnosis of PC is made after a
      patient with PA develops non-contiguous central nervous system (CNS) or systemic
      metastases. To date, only three cases of PC have been reportedly diagnosed on
      fine needle aspiration (FNA). Two of the reported cases were diagnosed on FNA of
      the cervical lymph nodes and one on FNA of the vertebral bone lesion. Herein, we
      present a case of PC, diagnosed on FNA of the liver lesion. In this case, we
      describe cytologic features of PC and compare them to histologic features of the
      tumor in the pituitary. Clinical behavior of tumor, pathogenesis of metastasis
      and immunochemical and prognostic markers will also be described.

PMID- 20806089
TI  - Lentivirus-mediated RNA interference of vascular endothelial growth factor in
      monkey eyes with iris neovascularization.
AB  - PURPOSE: To explore the in vivo anti-angiogenesis effects resulting from
      lentivirus-mediated RNAi of vascular endothelial growth factor (VEGF) in monkeys
      with iris neovascularization (INV). METHODS: Five specific recombinant lentiviral
      vectors for RNA interference, targeting Macaca mulatta VEGFA, were designed and
      the one with best knock down efficacy (LV-GFP-VEGFi1) in H1299 cells and RF/6A
      cells was selected by real-time PCR for in vivo use. A laser-induced retinal vein
      occlusion model was established in one eye of seven cynomolgus monkeys. In
      monkeys number 1, 3, and 5 (Group 1), the virus (1x10(8) particles) was
      intravitreally injected into the preretinal space of the animal's eye immediately
      after laser coagulation; and in monkeys number 2, 4, and 6 (Group 2), the virus
      (1x10(8) particles) was injected at 10 days after laser coagulation. In monkey
      number 7, a blank control injection was performed. In monkeys number 1 and 2,
      virus without RNAi sequence was used; in monkeys number 3 and 4, virus with
      nonspecific RNAi sequence was used; and in monkeys 5 and 6, LV-GFP-VEGFi1 was
      used. RESULTS: In monkey number 5, at 23 days after laser treatment, no obvious
      INV was observed, while fluorescein angiography of the iris revealed high
      fluorescence at the margin of pupil and point posterior synechiae. At 50 days
      after laser treatment, only a slight ectropion uvea was found. However, in the
      other eyes, obvious INV or hyphema was observed. The densities of new iridic
      vessels all significantly varied: between monkey number 5 and number 3 (36.01+/
      4.49/mm(2) versus 48.68+/-9.30/mm(2), p=0.025), between monkey number 3 and
      monkey number 7 (48.68+/-9.30/mm(2) versus 74.38+/-9.23/mm(2), p=0.002), and
      between monkey number 5 and number 7 (36.01+/-4.49/mm(2) versus 74.38+/
      9.23/mm(2), p<0.001). CONCLUSIONS: Lentivirus-mediated RNAi of VEGF may be a new
      strategy to treat iris neovascularization, while further studies are needed to
      investigate the long-term effect.

PMID- 20806090
TI  - Peptidylarginine deiminase type 2 is over expressed in the glaucomatous optic
      nerve.
AB  - PURPOSE: To determine levels of Peptidyl arginine deiminase 2 (PAD2) and its
      product protein-bound citrulline in cadaver eyes that suffered from normal
      tension glaucoma (NTG) compared to primary open angle glaucoma (POAG), and
      controls. METHODS: Western analysis, ELISA, and immunohistochemical analysis were
      performed with human tissues. RESULTS: We report over expression of PAD2 and
      higher levels of its product protein-bound citrulline in the optic nerve of
      normal tension glaucoma patients (NTG). CONCLUSIONS: This is the first report
      demonstrating that like in POAG, NTG also possesses elevated levels of both PAD2
      and protein-bound citrulline.

PMID- 20806091
TI  - MUC1 expression in Sjogren's syndrome, KCS, and control subjects.
AB  - PURPOSE: To quantify and compare human mucin 1 (MUC1) protein and mRNA expression
      in tears and conjunctival epithelial cells collected from Sjogren's syndrome
      (SS), non-Sjogren's keratoconjunctivitus sicca (KCS) and non-dry eyed (NDE)
      control subjects. METHODS: Seventy-six subjects were recruited for this study: 25
      SS (confirmed via American-European Consensus Criteria 2002), 25 KCS (confirmed
      by symptoms and Schirmer scores < or = 10 mm) and 26 NDE. Tears were collected
      using an eye-wash technique. Impression cytology was used to gather protein and
      mRNA from conjunctival epithelial cells. Soluble and membrane bound MUC1 were
      quantified via western blotting and MUC1 mRNA was quantified by real time qPCR.
      RESULTS: The SS group demonstrated significantly higher concentrations of soluble
      MUC1 (0.12 +/- 0.11 [SS]; 0.013 +/- 0.02 [KCS; p=0.001]; 0.0023 +/- 0.0024 [NDE;
      p<0.001]) and MUC1 mRNA (3.18 +/- 1.44 [SS]; 1.79 +/- 1.18 [KCS; p<0.05]; 1.60 +/
      0.74 [NDE; p<0.05]) compared to both KCS and NDE groups. Soluble MUC1 expression
      was also higher in the KCS group compared to the NDE group (p=0.02), where as
      MUC1 mRNA expression was similar in both KCS and NDE groups. Membrane bound MUC1
      expression differed only between the SS and NDE groups (0.005 +/- -0.003 [SS];
      0.003 +/- 0.002 [NDE; p=0.002]). CONCLUSIONS: These results demonstrate that SS
      subjects express greater quantities of MUC1 protein and mRNA compared to both KCS
      and control subjects. Increased soluble MUC1 expression was also found in KCS
      subjects compared to controls. Membrane bound MUC1 was present in higher
      concentration in SS versus NDE only. These significant changes in MUC1 expression
      may represent compensatory or protective responses to chronic insult to the
      ocular surface.

PMID- 20806093
TI  - Microbicidal and cytotoxic effects of functional water in vitro.
AB  - OBJECTIVE: Several kinds of functional water are used in the fields of food
      hygiene and medicine. The purpose of this study was to evaluate both the
      disinfection and cytotoxic effects of functional water in comparison with
      commonly used root canal irrigants such as sodium hypochlorite solution and
      hydrogen peroxide solution. METHOD AND MATERIALS: Three kinds of functional water
      were examined: alkaline electrolysis water (AEW), strong acid electrolyzed water
      (SAEW), and hypochlorous acid water (HAW). The disinfection effect was studied
      using Enterococcus faecalis and Candida albicans with or without organic
      substance. Each kind of functional water was applied to samples, and the colony
      formation was evaluated. The cytotoxic effect was evaluated by mitogenic assay
      (MTT) and alkaline phosphatase (ALPase) activity in pulp cells. RESULTS: SAEW and
      HAW showed microbicidal effects in the presence of organic substance, with an
      effect almost similar to sodium hypochlorite solution. AEW did not show any
      microbicidal effect. SAEW, AEW, and HAW at 10- and 1,000-times dilution did not
      inhibit the MTT assay and ALPase activity. The cytotoxicity of SAEW and HAW
      against pulp cells was mild compared to that of sodium hypochlorite solution.
      CONCLUSION: Functional water like SAEW and HAW have a good microbicidal effect
      under existing organic substance and are also mild to pulp cells.

PMID- 20806092
TI  - Comparison of three strains of diabetic rats with respect to the rate at which
      retinopathy and tactile allodynia develop.
AB  - PURPOSE: We compared three rat strains to determine if different strains develop
      early-stage diabetic retinopathy or sensory neuropathy at different rates.
      METHODS: Sprague Dawley, Lewis, and Wistar rats were made diabetic with
      streptozotocin. Diabetic and nondiabetic animals had retinal vascular pathology
      measured at eight months of diabetes. The number of cells in the retinal ganglion
      cell layer (GCL), retinal function (using electroretinography [ERG]), and retinal
      levels of inducible nitric oxide synthase (iNOS), cyclooxygenase2 (COX2), and
      vascular endothelial growth factor (VEGF) were measured at four months of
      diabetes. Tactile allodynia was assessed in hind paws at two months of diabetes.
      RESULTS: Diabetes of eight months' duration resulted in a significant increase in
      retinal degenerate capillaries and pericyte ghosts in Lewis and Wistar rats, but
      not in Sprague Dawley rats. A significant loss of cells in the GCL occurred only
      in diabetic Lewis rats, whereas Wistar and Sprague Dawley rats showed little
      change. Diabetes-induced iNOS and VEGF were statistically significant in all
      strains. Cyclooxygenase 2 (COX2) was significantly elevated in the Sprague Dawley
      and Wistar strains. Lewis rats showed a similar trend, however, the results were
      not statistically significant. All strains tended to show diabetes-induced
      impairment of dark-adapted b-wave amplitude, but only Sprague Dawley and Lewis
      strains had a significant reduction in latency. All strains showed significant
      tactile allodynia in peripheral nerves. CONCLUSIONS: At the durations studied,
      Lewis rats showed accelerated loss of both retinal capillaries and ganglion cells
      in diabetes, whereas diabetic Wistar rats showed degeneration of the capillaries
      without significant neurodegeneration, and Sprague Dawley rats showed neither
      lesion. Identification of strains that develop retinal lesions at different rates
      should be of value in investigating the pathogenesis of retinopathy.

PMID- 20806094
TI  - Bond strengths of an epoxy resin-based fiber post with four adhesive systems.
AB  - OBJECTIVES: To investigate the push-out bond strengths of one epoxy resin-based
      quartz-fiber post with four adhesive systems. METHOD AND MATERIALS: Forty-four
      single-rooted, single-canal teeth were randomly divided into four groups (n =
      11): One-step (One-Step + Duo-link; Bisco), Variolink II (Excite DSC + Variolink
      II; Ivoclar Vivadent), Panavia F (ED primer + Panavia F; Kuraray), and RelyX
      (RelyX Unicem; 3M ESPE). All teeth crowns were removed, and the roots were
      treated with root canal therapy. Four adhesive systems were employed for bonding
      of one type of quartz-fiber post, strictly according to the manufacturers'
      instructions. Ten roots in each group were transversely sectioned into cervical,
      middle, and apical third slices 2 mm thick, and the bond strengths were measured
      with the push-out test. The other root was processed for SEM analysis. Two-way
      ANOVA, one-way ANOVA, and Student-Newman-Keuls test were used for statistical
      analysis. RESULTS: The push-out bond strengths were 7.15 +/- 3.43 MPa (RelyX),
      12.48 +/- 9.33 MPa (One-step), 2.96 +/- 2.76 MPa (Panavia F), and 13.43 +/- 6.14
      MPa (Variolink II). Two-way ANOVA showed statistically significant differences
      among adhesive systems (P < .05) and root regions (P < .05). The bond strengths
      of One-step and Variolink II groups were statistically higher than those of RelyX
      and Panavia F groups. The bond strengths of the cervical region of One-step and
      Panavia F groups were statistically significantly higher than those of the other
      two regions. The SEM images showed uniform and long resin tags in One-step and
      Variolink II groups, whereas few or no resin tags were visible in the other two
      groups. CONCLUSION: The type of adhesive system and root region had a significant
      influence on the bond strengths of the adhesively luted fiber posts. Total
      etching technique achieved better bond strength than did the self-etching
      technique.

PMID- 20806095
TI  - Morphologic and developmental disturbances of permanent teeth following trauma to
      primary dentition in a selected group of Maltese children.
AB  - OBJECTIVE: This study investigated the effects of trauma to primary teeth,
      related by age at the time of injury and type of injury sustained, to the
      frequency and type of developmental disturbances in the permanent successor teeth
      in a representative population of Maltese children. METHOD AND MATERIALS: Thirty
      two children with 67 traumatized primary teeth were examined and any
      developmental disturbances of the corresponding permanent teeth recorded.
      RESULTS: Altogether, 52.2% of the permanent teeth exhibited developmental
      disturbances following trauma to their primary predecessors. The highest
      frequency of malformations was found following subluxation injuries. Intrusion
      injuries were associated with the most severe malformations. Age at the time of
      trauma to the primary dentition was a principal factor in the risk and severity
      of malformations developing in the permanent successors. CONCLUSION: The extent
      of malformation of the developing tooth germ was highly related to its
      developmental stage and to the severity and type of trauma sustained by the
      primary incisor.

PMID- 20806096
TI  - Surgical repositioning of a severely impacted mandibular second molar.
AB  - A 16-year-old girl was referred for surgical-orthodontic treatment with the chief
      complaint of an unerupted mandibular left second molar. With the exception of
      this molar, the patient had a fully erupted permanent dentition. A panoramic
      radiograph showed a horizontally impacted mandibular left second molar beneath a
      mesially impacted third molar. A surgical approach was used to upright and
      reposition the impacted second molar. When a molar is severely impacted, surgical
      uprighting may provide a viable option when other treatment modalities are
      contraindicated. This case shows an example of successful use of a surgical
      approach for uprighting and repositioning an impacted molar. The impacted molar
      was moved into its proper position with surgical exposure, after which it showed
      good stability.

PMID- 20806097
TI  - Self-reported complications with lip and tongue piercing.
AB  - OBJECTIVES: Owing to the overwhelming popularity of oral piercing, general
      practitioners should be prepared to address complications arising as a result of
      oral piercing and to provide patients with accurate information. The purpose of
      this cross-sectional study was to assess the prevalence of early and late
      complications associated with lip and tongue piercing in a population obtained
      from a nondental setting. Possible cofactors were evaluated. METHOD AND
      MATERIALS: The study cohort included 130 lip and 80 tongue piercings.
      Participants were asked to complete a questionnaire to determine demographic
      data, smoking habits, characteristics of the piercing worn (time since piercing,
      material-plastic or metal), postpiercing complications, and possible cofactors.
      RESULTS: Prevalence of early piercing complications was 87.83%. Although there
      was no statistically significant difference in the overall prevalence of early
      postpiercing complications after lip or tongue piercing, the type of complication
      differed significantly according to the piercing location. Significant cofactors
      for early complications were oral hygiene behavior, gender, and the person who
      performed the piercing. The highest prevalence of late complications was found to
      be recurrent infections and gingival recessions. As cofactors, time since
      piercing and oral hygiene behavior had a significant impact on late
      complications. CONCLUSION: Early complications after oral piercing are frequent.
      Oral health care might be an important tool to minimize early and late
      postpiercing complications. Owing to the high prevalence of late complications
      especially after median lip piercing-persons with oral piercing should attend
      regular dental checks and receive professional advice on tooth cleaning and oral
      hygiene.

PMID- 20806098
TI  - Management of multiple and isolated gingival recession sites with periodontal
      plastic surgical procedures--a case report.
AB  - Multiple recession defects in the dentition of an individual are routinely
      encountered in clinical practice and as such present a challenge for management.
      Periodontal plastic surgical procedures aim to restore both gingival esthetics as
      well as function in these defects. This case report highlights four periodontal
      plastic surgical techniques (the coronally advanced flap for single and multiple
      recession defects, double papillae with subepithelial connective tissue graft,
      and envelope technique with subepithelial connective tissue graft) that have been
      employed for root coverage in isolated Miller Class I recession defects in a 35
      year-old individual. Three of the techniques resulted in 100% root coverage in
      all treated sites, while the site treated with subepithelial connective graft by
      envelope technique resulted in 83.3% root coverage. Treatment also helped to
      resolve hypersensitivity and achieved satisfaction of the patient's esthetic
      concerns.

PMID- 20806099
TI  - Longevity of frictional telescopic crowns in the severely reduced dentition: 3
      year results of a longitudinal prospective clinical study.
AB  - OBJECTIVES: The longevity of frictional telescopic crowns (FTC) in severely
      reduced dentitions with 1 to 3 remaining teeth per jaw has not yet been studied
      prospectively and exclusively. Aims of this study were to estimate risks of
      telescope loss and abutment tooth loss and to determine abutment tooth mobility
      over time. METHOD AND MATERIALS: A total of 74 patients with severely reduced
      dentitions received 82 telescopic removable partial dentures (TRPDs) retained
      with 173 FTCs. Dentures were reexamined after 1 week and 3, 6, 12, 18, 24, 30,
      and 36 months. Tooth mobility was monitored with Periotest values. Adjuvant
      therapies were carried out if necessary. Survival probabilities of telescopes and
      abutment teeth as well as the influence of clinical factors (age, sex, jaw,
      vitality, opposing dentition, axis inclination, end Periotest value, crown
      length, crown margin quality, wearing mode, tooth types, abutment distribution,
      number of telescopes) were calculated with Kaplan-Meier estimators. The relative
      risks for telescope loss were calculated with Cox regression. RESULTS: The
      survival rate was 93.9% for abutment teeth and 87.5% for telescopes. Number of
      telescopes, abutment distribution, vitality, and gender as factors influenced the
      survival rates (Kaplan-Meier). In combination with the jaw as a factor, these
      affected the risk for telescope loss (Cox regression). Periotest values (mean of
      abutment teeth per examination) decreased significantly (P < .0001). Altogether,
      11% of teeth fractured and 4.6% of teeth were extracted. Patients were mostly
      very satisfied. CONCLUSION: TRPDs proved to be a favorable treatment concept for
      severely reduced dentitions. FTCs can be considered as elements with a good
      benefit-maintenance relation. A general increase of abutment tooth mobility could
      not be verified.

PMID- 20806100
TI  - Cleaning efficacy of an apical negative-pressure irrigation system at different
      exposure times.
AB  - OBJECTIVE: Recent studies have shown that the apical negative-pressure irrigation
      system EndoVac (Discus Dental) produces better disinfection and cleanliness at
      the apical third of root canals than current irrigation methods using positive
      pressure. The aim of this histologic study was to compare the EndoVac system at
      two different exposure times to the traditional positive-pressure irrigation
      technique for root canal cleaning efficacy and to measure the volume of
      irrigation at the apical third. METHOD AND MATERIALS: Fifty extracted human
      incisors, canines, and premolars (with one canal) were used. All teeth were
      stored in sterile saline and then randomly assigned to one of three experimental
      groups of 15 each. All teeth were cleaned and shaped at working length using
      Profile Series 29 (Dentsply Tulsa) to a size 6 (ISO size 36) or larger depending
      on the first instrument to bind at the apical third. After working length was
      reached with the master apical file, apical irrigation was accomplished with 6%
      sodium hypochlorite (NaOCl) over a predetermined time for each group as follows:
      group 1, EndoVac for 210 seconds; group 2, EndoVac for 150 seconds; group 3,
      traditional positive-pressure irrigation for 210 seconds. The amount of debris
      left in the canals was quantified at 1 and 3 mm from working length. RESULTS: No
      statistical differences were found at 3 mm from working length. At 1 mm from
      working length, an overall test of association was significant when comparing
      across the three groups (P = .03). CONCLUSION: The apical negative-pressure
      irrigation system EndoVac has the potential to achieve significantly better root
      canal cleaning at the apical third of root canals and in less exposure time than
      required with traditional positive-pressure irrigation.

PMID- 20806101
TI  - Schwannoma in the lower lip mucosa: unexpected diagnosis.
AB  - Schwannoma is a benign tumor arising from nerve-sheath Schwann cells. When it
      affects the mouth, the lips are rarely involved. A MEDLINE search in the English
      literature from 1969 to 2009 revealed only 17 documented cases of schwannomas of
      the lip. This report describes the unusual case of a 52-year-old man who
      developed a schwannoma of the lower lip. Histopathologic examination and
      immunohistochemical staining studies were performed. Although rare, schwannoma
      should be considered in the differential diagnosis of any nodule or mass in the
      oral mucosa.

PMID- 20806102
TI  - The influence of saliva on the dissolution of calcium fluoride after application
      of different fluoride gels in vitro.
AB  - OBJECTIVE: To determine the formation and dissolution of calcium fluoride on the
      enamel surface after application of two fluoride gel-saliva mixtures. METHOD AND
      MATERIALS: From each of 80 bovine incisors, two enamel specimens were prepared
      and subjected to two different treatment procedures. In group 1, 80 specimens
      were treated with a mixture of an amine fluoride gel (1.25% F-; pH 5.2; 5
      minutes) and human saliva. In group 2, 80 enamel blocks were subjected to a
      mixture of sodium fluoride gel (1.25% F; pH 5.5; 5 minutes) and human saliva.
      Subsequent to fluoride treatment, 40 specimens from each group were stored in
      human saliva and sterile water, respectively. Ten specimens were removed after
      each of 1 hour, 24 hours, 2 days, and 5 days and analyzed according to potassium
      hydroxide-soluble fluoride. RESULTS: Application of amine fluoride gel resulted
      in a higher amount of potassium hydroxide-soluble fluoride than did sodium
      fluoride gel 1 hour after application. Saliva exerted an inhibitory effect
      according to the dissolution rate of calcium fluoride. However, after 5 days,
      more than 90% of the precipitated calcium fluoride was dissolved in the amine
      fluoride group, and almost all potassium hydroxide-soluble fluoride was lost in
      the sodium fluoride group. Calcium fluoride apparently dissolves rapidly, even at
      almost neutral pH. CONCLUSION: Considering the limitations of an in vitro study,
      it is concluded that highly concentrated fluoride gels should be applied at an
      adequate frequency to reestablish a calcium fluoride-like layer.

PMID- 20806103
TI  - Salivary calcium concentration in relation to periodontal health of female
      tobacco smokers: a pilot study.
AB  - OBJECTIVE: The aim of this pilot study was to assess the possibility of
      differences in the calcium concentration of the saliva between smoker and
      nonsmoker patients with or without periodontitis. METHOD AND MATERIALS: A total
      of 44 women were enrolled in this study. Exclusion criteria were severe general
      health problems, the prescription of medication, and fewer than 16 remaining
      teeth. The study population comprised 24 smokers (4 periodontitis free, 16 with
      chronic and 4 with aggressive periodontitis; mean age 50.2 years +/- 6.9) and 20
      nonsmokers (10 periodontitis free, 9 with chronic and 1 with aggressive
      periodontitis; mean age 54.7 years +/- 15.6). Clinical parameters (bone loss;
      plaque, gingival and calculus indices; and pocket depth) were recorded, and
      stimulated saliva samples were collected. The calcium concentration of each
      saliva sample was measured by atomic absorption spectrophotometry. Statistical
      analysis was performed with the MANOVA test. RESULTS: The mean salivary calcium
      level in the smokers (57.76 MUg/mL +/- 18.8) was significantly (P < .05) higher
      than in the nonsmokers (44.6 MUg/mL +/- 7.8). Periodontal examination revealed
      significantly greater bone loss, a deeper mean probing depth, and a higher amount
      of calculus (P < .05) among the smokers. However, there were no statistically
      significant differences between the smokers and the nonsmokers as concerns the
      plaque and bleeding indices. CONCLUSIONS: Within their limits, the present
      findings seem to indicate that patients with periodontitis who smoke exhibit
      higher salivary calcium levels than those in nonsmokers. However, the clinical
      significance of these findings remains to be determined in large-scale controlled
      studies.

PMID- 20806104
TI  - Comparison of curing depth of a colored polyacid-modified composite resin with
      different light-curing units.
AB  - OBJECTIVE: To compare the depth of cure (DoC) of a colored polyacid-modified
      composite resin (PAM-C) with a traditional PAM-C and a fine hybrid composite
      resin using different light-curing units and different radiant energies. METHOD
      AND MATERIALS: The DoC of the PAM-C Twinky Star (Voco, all shades), the PAM-C
      Glasiosite (Voco), and the composite resin Z100 (3M ESPE) shades A2 and A4 was
      determined using a penetrometer test method. The materials were cured in bulk
      using a halogen-based unit (Elipar Trilight, E = 18 J/cm2 and E = 32 J/cm2; 3M
      ESPE) and an LED curing unit (Elipar Freelight 2, E = 20 J/cm2; 3M ESPE) in split
      stainless steel molds. Immediately after curing, the height (mm) of the cured
      material was measured and taken as the DoC. Ranking of means was performed by
      Student-Newman-Keuls multiple comparison test, and statistically significant
      differences among mean values were detected with ANOVA. RESULTS: Mean DoC for all
      materials and shades varied as follows: 4.705 to 8.870 mm (E = 32 J/cm2); 3.672
      to 8.050 mm (E = 20 J/cm2); and 4.090 to 7.357 mm (E = 18 J/cm2). Two-way ANOVA
      revealed that the DoC depended significantly (P < .001) on the shade of the
      material and the curing device. Moreover, there was a significant interaction (P
      < .001) between the latter, indicating that the effect of the energy densities
      differed quantitatively among the shades. CONCLUSIONS: In this study, DoC
      differed significantly among the materials and the shades. Twinky Star shade blue
      showed the highest DoC compared to Glasiosite and Z100 shades A2 and A4. The
      curing device with the highest energy density exhibited the highest curing
      depths.

PMID- 20806105
TI  - Exploring newer cardioprotective strategies: omega-3 fatty acids in perspective.
AB  - In the 1980s, observational retrospective studies showed an inverse relation
      between coronary heart disease (CHD) and consumption of fish containing fatty
      acids that belong to the omega (omega)-3 family. Large case-control studies and
      prospective intervention trials consistently showed that omega-3 fatty acids
      supplementation lowers fatal myocardial infarction (MI) and sudden cardiac death.
      By analysing the strengths of the results of individual studies and how the meta
      analyses agree with them, putting together relevant backgrounds, and identifying
      open questions, the following findings/directions emerge. (i) Dietary and non
      dietary intake of omega-3 fatty acids reduces overall mortality, mortality due to
      MI, and sudden death in patients with CHD; (ii) Fish oil consumption directly or
      indirectly affects cardiac electrophysiology. Fish oil reduces heart rate, a
      major risk factor for sudden death; (iii) Among patients with implantable
      cardioverter defibrillators, omega-3 fatty acids do not reduce the risk of
      ventricular tachycardia/ventricular fibrillation and may actually be pro
      arrhythmic; (iv) The consumption of omega-3 fatty acids leads to a 10-33% net
      decrease of triglyceride levels. The effect is dose-dependent, larger in studies
      with higher mean baseline triglyceride levels, and consistent in different
      populations (healthy people, people with dyslipidaemia, diabetes, or known
      cardiovascular risk factors); (v) Outcomes for which a small beneficial effect
      omega-3 fatty acids is found include blood pressure (about 2 mmHg reduction), re
      stenosis rates after coronary angioplasty (14% reduction), and exercise tolerance
      testing. Major experimental data provide strength (biological plausibility) for
      these findings, and define directions for newer clinical trials with omega-3
      fatty acids.

PMID- 20806106
TI  - Comparative study of coagulation and thrombin generation in the portal and
      jugular plasma of patients with cirrhosis.
AB  - Portal vein thromboses are frequent in cirrhotic patients and may be favoured by
      hypercoagulability in the splanchnic venous system. The coagulation balance and
      thrombin generation (TG) were evaluated in platelet-free plasma obtained from
      portal and systemic blood samples in 28 cirrhotic patients while undergoing
      transjugular intrahepatic porto-systemic shunt. TG assay (TGA) was performed with
      all samples from cirrhotic patients and with plasma samples from 14 healthy
      controls, with varying concentrations of tissue factor and phospholipids, with or
      without thrombomodulin. Screening tests and specific assays were also performed
      and activated partial thromboplastin time was shorter in portal plasma samples
      with higher FVIII and lower protein C levels, well correlated with Child-Pugh
      scores, and higher D-dimers and F1+2 levels However, all TGA parameters were
      similar in portal and jugular samples, possibly due in part to similar
      concentrations of factor II and antithrombin in these two sites of plasma
      sampling. TGA showed lower thrombin peaks and endogenous thrombin potential
      values in cirrhotic plasma compared to those of healthy controls. Importantly, a
      resistance to thrombomodulin that well correlated with factor VIII and PC levels,
      was evidenced in all samples from patients with cirrhosis, and was more
      significant in those from severely affected cases. This study therefore supports
      the existence of a relative hypercoagulability in the portal vein of cirrhotic
      patients that is likely due to protein C/S deficiency and to high FVIII levels.

PMID- 20806107
TI  - Cost-effectiveness of rivaroxaban versus enoxaparin for the prevention of
      postsurgical venous thromboembolism in Canada.
AB  - This study aimed to evaluate the cost-effectiveness of prophylaxis with
      rivaroxaban vs. enoxaparin in the prevention of venous thromboembolism (VTE)
      after total hip replacement (THR) and total knee replacement (TKR) from the
      perspective of the Canadian healthcare system. A model was developed that
      included both acute VTE (represented as a decision tree) and long-term
      complications (represented as a Markov process with one-year cycles). Transition
      probabilities were derived from phase III clinical trials comparing rivaroxaban
      with enoxaparin and published literature. Costs were derived from the Ontario
      Case Costing Initiative and publicly available sources. Utilities were derived
      from published literature. The model reported VTE event rates, quality-adjusted
      life expectancy and direct medical costs over a five-year horizon. Costs are
      reported in 2007 Canadian Dollars (C$). When rivaroxaban and enoxaparin are
      compared in patients undergoing THR, rivaroxaban dominates enoxaparin. That is,
      rivaroxaban is associated with improved health outcomes as measured by increased
      quality-adjusted life years (QALYs; 0.0006) and fewer symptomatic VTE events
      (0.0061), and also with lower cost (savings of C$300) per patient. Similarly,
      rivaroxaban dominates enoxaparin in patients undergoing TKR, achieving a gain of
      0.0018 QALYs, a reduction of 0.0192 symptomatic venous thromboembolic events and
      savings of C$129 per patient. Rivaroxaban is a cost-effective alternative to
      enoxaparin for VTE prophylaxis in patients undergoing THR and TKR. Over a five
      year horizon, rivaroxaban dominated enoxaparin in the prevention of VTE events in
      patients undergoing THR and TKR, providing more quality-of-life benefit at a
      lower cost.

PMID- 20806108
TI  - C1 inhibitor, a multi-functional serine protease inhibitor.
AB  - C1 inhibitor (C1INH) is a serpin that regulates both complement and contact
      (kallikrein-kinin) system activation. It consists of a serpin domain that is
      highly homologous to other serpins and an amino terminal non-serpin mucin-like
      domain. Deficiency of C1INH results in hereditary angioedema, a disease
      characterised by episodes of angioedema of the skin or the mucosa of the
      gastrointestinal tract or the oropharynx. Although early data suggested that
      angioedema was mediated via complement system activation, the preponderance of
      the data indicate that bradykinin is the mediator. In the past few years, it has
      become apparent that C1INH has additional anti-inflammatory functions independent
      of protease inhibition. These include interactions with leukocytes that may
      result in enhanced phagocytosis, with endothelial cells via E- and P-selectins
      that interfere with leukocyte rolling and in turn results in suppression of
      transmigration of leukocytes across the endothelium, and interactions with
      extracellular matrix components that may serve to concentrate C1INH at sites of
      inflammation. In addition, C1INH suppresses gram negative sepsis and endotoxin
      shock, partly via direct interaction with endotoxin that interferes with its
      interaction with macrophages, thereby suppressing tumour necrosis factor-a and
      other inflammatory mediators. C1INH treatment improves outcome in a number of
      disease models, including sepsis and other bacterial infections, possibly
      malaria, ischaemia-reperfusion injury (intestinal, hepatic, muscle, cardiac,
      brain), hyper-acute transplant rejection, and other inflammatory disease models.
      Recent data suggest that this effectiveness is the result of mechanisms that do
      not require protease inhibition, in addition to both complement and contact
      system activation.

PMID- 20806109
TI  - Removal of elevated circulating angiopoietin-2 by plasma exchange--a pilot study
      in critically ill patients with thrombotic microangiopathy and anti-glomerular
      basement membrane disease.
AB  - In critically ill patients, the massive release of angiopoietin-2 (Ang-2) from
      Weibel-Palade bodies interferes with protective angiopoietin-1 (Ang-1)/Tie2
      signalling in endothelial cells, thus leading to vascular inflammation and
      subsequent organ-dysfunction. We hypothesised that plasma exchange (PE) is
      efficient for lowering excess Ang-2 levels in critically ill patients with
      thrombocytic microangiopathy (TMA) or anti-glomerular basement membrane (anti
      GBM) disease. Plasma Ang-1 and Ang-2 were measured by immuno-luminometric assays
      in patients with TMA (n=9) or anti-GBM disease (n=4) before and after up to four
      PE sessions. Twenty apparently healthy volunteers served as controls. Median
      (IQR) plasma levels of Ang-2 were markedly increased in patients with TMA (7.3
      (2.4-21.1) ng/ml) and anti-GBM disease (5.8 (3.4-7.0) ng/ml) compared to healthy
      controls (1.0 (0.9-1.4) ng/ml, p <0.001). Moreover, Ang-1 plasma levels were
      decreased in both, TMA (1.02 (0.62-1.62) ng/ml) and anti-GBM disease patients
      (0.74 (0.59-3.62) ng/ml) compared to healthy controls (2.5 (1.93-3.47) ng/ml, p
      <0.005). During a total of 32 treatments, PE effectively lowered elevated mean
      (SD) Ang-2 plasma levels by 36.7 +/- 19.6% per treatment (p <0.0001), whereas low
      Ang-1 plasma levels remained unchanged (0.3 +/- 58.5%; p=0.147). Ang-2 levels
      declined to almost normal values during <=4 PE treatments (Friedman's test
      p<0.0001). PE is an effective method to remove excess circulating Ang-2. It
      remains to be elucidated if the removal of Ang-2 is crucial to ameliorate
      endothelial damage in critically ill patients with severely altered endothelial
      integrity.

PMID- 20806110
TI  - Management of dental extraction in patients undergoing anticoagulant treatment.
      Results from a large, multicentre, prospective, case-control study.
AB  - Following favourable results from a previous study, a large, multicentre,
      prospective, case-control study was performed to further assess the incidence of
      bleeding complications after dental extraction in patients taking oral
      anticoagulant therapy (OAT). Four hundred fifty-one patients being treated with
      warfarin who required dental extraction were compared with a control group of 449
      non-anticoagulated subjects undergoing the same procedure. In the warfarin
      treated group, the oral anticoagulant regimen was maintained unchanged, such that
      the patients had an International Normalised Ratio ranging between 1.8 and 4, and
      local haemostatic measures (i.e. fibrin sponges, silk sutures and gauzes
      saturated with tranexamic acid) were adopted. All the procedures were performed
      in an outpatient setting. Seven bleeding complications occurred in the OAT group
      and four in the control group; the difference in the number of bleeding events
      between the two groups was not statistically significant (OR=1.754; 95% CI 0.510 
      6.034; p=0.3727). No post-operative late bleeds requiring hospitalisation and/or
      blood transfusions were recorded, and the adjunctive local haemostatic measures
      were adequate to stop the bleeding. The results of our protocol applied in this
      large, multicenter study show that dental extractions can be performed easily and
      safely in anticoagulated outpatients without any modification of the ongoing
      anticoagulant therapy, thus minimising costs and reducing discomfort for
      patients.

PMID- 20806113
TI  - Interaction of PF4 (CXCL4) with the vasculature: a role in atherosclerosis and
      angiogenesis.
AB  - Platelet factor-4 (PF4), a platelet-derived chemokine, has two important
      functions in the vasculature. It has a pro-atherogenic role while also having
      anti-angiogenic effects. The activity of platelet factor-4 (PF4), unlike other
      chemokines that bind to specific receptors, depends on its unusually high
      affinity for proteoglycans and other negatively charged molecules. High affinity
      for heparan sulfates was thought to be central to all of PF4's biological
      functions. However, other mechanisms have been described such as direct growth
      factor binding, activation of the CXCR3B chemokine receptor isoform that is
      present in some vascular cells or binding to lipoprotein-related protein-1
      (LRP1). Furthermore, PF4 also binds to integrins with affinities similar to
      matrix molecules. These interactions may explain the effects of PF4 in healthy
      and pathological tissues. However, the mechanisms involved in PF4's activity are
      complex and may depend on a given tissue or localisation. Overall, while much is
      already known about PF4, its specific role in atherosclerosis and angiogenesis
      remains still to be clarified.

PMID- 20806112
TI  - Factor XII: new life for an old protein.
AB  - Ratnoff and his coworkers recognised that factor XII (XII) stimulates cell growth
      and activates mitogen-activated protein kinase. We determined the receptor(s) for
      this function and the consequence of this signalling pathway. Investigations show
      that the urokinase plasminogen activator receptor serves as the XII binding site
      on cultured umbilical vein endothelial cells. When XII binds, it stimulates
      ERK1/2 and Akt S473 phosphorylation. These events are distinct because when cell
      mTORC2 is absent, XII phosphorylates ERK1/2 but not Akt S473. Zymogen XII is an
      equal stimulator of signalling as XIIa or inhibitor-treated XIIa. Peptides from
      uPAR domain 2 block XII binding and ERK1/2 and Akt phosphorylation. Furthermore,
      antibodies to the integrins beta1 and alpha5 block XII signalling. Likewise,
      inhibitors to the EGFR block XII-induced phosphorylation events. XII stimulates
      cell growth and proliferation. XII induces angiogenesis ex vivo in normal aortic
      sprouts and in vivo in matrigel plugs in normal mice, but not in aorta from uPAR
      knockout mice or matrigel plugs placed into uPAR-deleted mice. Skin biopsies
      constitutively or in a wound nine days after injury show reduced CD31 antigen
      expression in specimens from XII knockout mice compared to wild-type mice. These
      studies indicate that XII stimulates angiogenesis, a physiologic function
      independent of contact activation.

PMID- 20806111
TI  - Hypodysfibrinogenaemia due to production of mutant fibrinogen alpha-chains
      lacking fibrinopeptide A and polymerisation knob 'A'.
AB  - Inherited disorders of fibrinogen are rare and affect either the quantity
      (hypofibrinogenaemia and afibrinogenaemia) or the quality of the circulating
      fibrinogen (dysfibrinogenaemia) or both (hypodysfibrinogenaemia). Extensive
      allelic heterogeneity has been found for all these disorders: in congenital
      afibrinogenaemia for example more than 40 mutations, the majority in FGA , have
      been identified in homozygosity or in compound heterozygosity. Numerous mutations
      have also been identified in patients with hypofibrinogenaemia, many of these
      patients are in fact heterozygous carriers of afibrinogenaemia mutations. Despite
      the number of genetic analyses performed, the study of additional patients still
      allows the identification of novel mutations. Here we describe the
      characterization of a novel FGA intron 2 donor splice-site mutation (Fibrinogen
      Montpellier II) identified in three siblings with hypodysfibrinogenaemia.
      Functional analysis of RNA produced by the mutant minigene in COS-7 cells
      revealed that the mutation led to the in-frame skipping of exon 2. Western blot
      analysis of COS-7 cells expressing an exon 2 deleted FGA cDNA revealed that an
      alpha-chain lacking exon 2, which codes in particular for fibrinopeptide A and
      polymerisation knob 'A', has the potential to be assembled into a hexamer and
      secreted. Analysis of precipitated fibrinogen from patient plasma showed that the
      defect leads to the presence in the circulation of alpha-chains lacking knob 'A'
      which is essential for the early stages of fibrin polymerisation. Fibrin made
      from purified patient fibrinogen clotted with thrombin displayed thinner fibers
      with frequent ends and large pores.

PMID- 20806114
TI  - An optimised, rapid chromogenic assay, specific for measuring direct factor Xa
      inhibitors (rivaroxaban) in plasma.

PMID- 20806115
TI  - Argatroban administration reduces leukocyte adhesion and improves capillary
      perfusion within the intestinal microcirculation in experimental sepsis.
AB  - Co-activation of pro-coagulatory pathways in sepsis may result in disseminated
      intravascular coagulation and contributes to microvascular dysfunction. We
      investigated the effects of the direct thrombin inhibitor, argatroban (ARG), on
      the sepsis-induced impairment of the intestinal microcirculation (capillary
      perfusion, leukocyte adhesion) and the vascular contractility in rats. Forty male
      Lewis rats were randomly assigned to one of four groups: sham surgery (SHAM),
      experimental sepsis (colon ascendens stent peritonitis--CASP), CASP+ARG, and
      SHAM+ARG. At 16 hours after colon stent insertion (or sham surgery), 2 mg/kg
      argatroban or buffer were given intravenously, and 1 hour thereafter, intravital
      microscopy was performed. In addition, experiments to study the impact of ARG on
      vascular contractility were conducted in vitro . ARG administration in CASP rats
      significantly increased functional capillary density in mucosal (+128%) and
      muscular layers (longitudinal: +42%; circular: +64%) and decreased the number of
      firmly adhering leukocytes in the intestinal submucosa compared to untreated
      animals. In vitro findings indicated a vasodilating effect of ARG. ARG
      administration during experimental sepsis improved intestinal microcirculation by
      preserving functional capillary density, an indicator of microvascular perfusion,
      and by reducing leukocyte adherence to the endothelium in submucosal venules.

PMID- 20806116
TI  - Allele-specific transcription of the PAI-1 gene in human astrocytes.
AB  - The 4G allele of the PAI-1 -675(4G/5G) insertion/deletion promoter polymorphism
      has been associated with elevated plasma levels of PAI-1 and an increased risk of
      myocardial infarction. However, this allele has also been associated with a
      reduced risk of ischaemic stroke. In the brain, PAI-1 is mainly produced by
      astrocytes, and can reduce the neurotoxic effects exerted by tissue-type
      plasminogen activator during pathophysiologic conditions. The aim of the present
      study was to investigate whether the PAI-1 -675(4G/5G) polymorphism and the
      linked -844A/G polymorphism affect transcriptional activity of the PAI-1 gene in
      human astrocytes. Haplotype chromatin immunoprecipitation (haploChIP) was used in
      order to quantify allele-specific promoter activity in heterozygous cells.
      Protein-DNA interactions were investigated by electrophoretic mobility shift
      assay (EMSA). A clear allele-specific difference in PAI-1 gene expression was
      observed in astrocytes, where the haplotype containing the 4G and the -844A
      alleles was associated with higher transcriptional activity compared to the 5G
      and -844G-containing haplotype. EMSA revealed an allele-specific binding of
      nuclear proteins to the 4G/5G site as well as to the -844A/G site. Supershift
      experiments identified specific binding of the transcription factors Elf-1 and
      Elk-1 to the -844G allele. The relative impact of the different sites on allele
      specific PAI-1 promoter activity remains to be determined. We demonstrate that
      common polymorphisms within the PAI-1 promoter affect transcriptional activity of
      the PAI-1 gene in human astrocytes, thus providing a possible molecular genetic
      mechanism behind the association between PAI-1 promoter variants and ischaemic
      stroke.

PMID- 20806118
TI  - Eradication of hospital-acquired venous thromboembolism.

PMID- 20806117
TI  - Effect of apixaban, an oral and direct factor Xa inhibitor, on coagulation
      activity biomarkers following acute coronary syndrome.
AB  - Apixaban is an oral, direct factor Xa inhibitor under development for secondary
      prevention in acute coronary syndrome (ACS). Apixaban's effect on D-dimer and
      prothrombin fragment 1.2 (F1.2) (coagulation activity biomarkers ) was determined
      in a randomised, double-blinded, placebo-controlled, phase 2 study. Patients
      (n=1,715) with either ST- segment elevation or non-ST-segment elevation ACS
      received either placebo or apixaban 2.5 mg twice daily, 10 mg once daily, 10 mg
      twice daily or 20 mg once daily for six months. Samples were obtained at baseline
      (before study drug administration), week 3 and week 26. Apixaban plasma
      concentrations were measured directly by liquid chromatography/mass spectometry,
      and anti-Xa activity was determined using apixaban as a reference standard. D
      dimer and F 1.2 were measured using ELISA-based methods. Most patients had
      elevated D-dimer and F1.2 levels at baseline. Both coagulation activity
      biomarkers decreased by week 3 in all treatment groups, but to a greater degree
      with apixaban than placebo (p<0.001). In a multivariable analysis, apixaban was
      independently associated with a change in biomarkers over time (p<0.0001). While
      the overall decrease did not differ significantly among the three highest
      apixaban doses, F1.2 was suppressed more rapidly by the 10 mg once daily than the
      2.5 mg twice daily dose (p<0.05). There was a strong and direct relationship
      between apixaban plasma concentrations and anti-Xa-apixaban levels, and an
      inverse relationship for both measures with coagulation activity biomarkers. In
      conclusion, the oral direct factor Xa inhibitor apixaban significantly reduced
      coagulation activity biomarkers among patients with ACS. The 10 mg once daily
      dose reduced thrombin generation (F 1.2) and fibrin formation (D-dimer) more
      rapidly and robustly than the 2.5 mg twice daily dose. The effect on both D-dimer
      and F 1.2 was apixaban concentration-and factor Xa inhibition dependent, durable
      and provided general guidance for dose selection in phase 3 investigation.

PMID- 20806119
TI  - Incidental venous thromboembolism in ambulatory cancer patients receiving
      chemotherapy.
AB  - While the association between cancer and symptomatic venous thromboembolism (VTE)
      is well established, the incidence and risk factors for incidental VTE in cancer
      patients remain unclear. The medical records of 1,921 consecutive cancer patients
      starting chemotherapy from January 2003 up to March 2009 were identified.
      Patients with a positive history of VTE were excluded. Pre-existing signs of VTE,
      kind and stage of malignancy, first and subsequent lines of chemotherapy, and all
      follow-up computed tomography (CT) scans were analysed. The primary outcome was
      incidental VTE. Overall, there were 101 (5.3%) VTE, 62 (3.2%) incidental and 39
      (2.0%) symptomatic during a median of eight months (range 3-72). The incidence on
      CT scans was 0.58% (95%CI: 0.44-0.74). Incidental VTE included 24 pulmonary
      embolism, 28 deep venous thrombosis of the extremities, and 10 thromboses of the
      cava or splanchnic veins. Half of the incidental VTE occurred in the first 3-6
      months of chemotherapy with a relatively higher incidence in gynecological and
      lung cancers. The presence of metastases, high leukocyte count, and platin-based
      chemotherapy increased the risk up to three-fold. All patients with incidental
      VTE regardless the location received half to full therapeutic doses of low
      molecular-weight heparin for a minimum of three months. In summary, incidental
      VTE is a relative common finding in patients with solid tumours, especially in
      the first months of chemotherapy. Further research is needed to understand the
      natural history of incidental thrombosis in order to develop adequate management
      guidelines.

PMID- 20806120
TI  - Fondaparinux thromboprophylaxis-associated heparin-induced thrombocytopenia
      syndrome complicated by arterial thrombotic stroke.

PMID- 20806122
TI  - Fluoxetine inhibition of 5-HT-potentiated platelet aggregation in whole blood.

PMID- 20806121
TI  - BF0801, a novel adenine derivative, inhibits platelet activation via
      phosphodiesterase inhibition and P2Y12 antagonism.
AB  - Though antiplatelet drugs are proven beneficial to patients with coronary heart
      disease and stroke, more effective and safer antiplatelet drugs are still needed.
      In this study we report the antiplatelet effects and mechanism of BF0801, a novel
      adenine derivative. BF0801 dramatically inhibited platelet aggregation and ATP
      release induced by ADP, 2MeSADP, AYPGKF, SFLLRN or convulxin without affecting
      shape change in vitro . It also potentiated the inhibitory effects of adenosine
      based P2Y12 antagonist AR-C69931MX or phosphodiesterase (PDE) inhibitor IBMX on
      platelet aggregation. The cAMP levels in both resting and forskolin-stimulated
      platelets were increased by BF0801 suggesting its PDE inhibitor activity, which
      is further confirmed by the concentration-dependent suppression of BF0801 on the
      native and recombinant PDE. Similar to AR-C69931MX, BF0801 drastically inhibited
      2MeSADP- induced adenylyl cyclase inhibition in platelets indicating its P2Y12
      antagonism activity, which is substantiated by the inhibition of BF0801 on the
      interaction between ADP and P2Y12 receptor expressed in CHO-K1 cells measured by
      atomic force microscopy. Moreover, we confirmed the antiplatelet effects of
      BF0801 using platelets from rats intravenously given BF0801. In summary, for the
      first time we developed a novel adenine derivative bearing dual activities of PDE
      inhibition and P2Y12 antagonism, which may have therapeutic advantage as a
      potential antithrombotic drug.

PMID- 20806123
TI  - Evaluation of commercial von Willebrand factor collagen binding assays to assist
      the discrimination of types 1 and 2 von Willebrand disease.
AB  - This study reports on the evaluation of seven commercial von Willebrand factor
      (VWF) collagen binding (VWF:CB) assays to potentially assist the discrimination
      of types 1 and 2 von Willebrand disease (VWD). Samples from 25 patients with type
      1 VWD, of varying severity, were co-tested with 16 samples from patients with
      types 2A or 2B VWD, plus various control samples, using each commercial VWF:CB
      assay assessed against our standard (reference) in-house VWF:CB assay, as well as
      our in-house VWF antigen (VWF:Ag) and ristocetin cofactor (VWF:RCo) assays.
      Commercial VWF:CB assays varied in their ability to discriminate types 1 and
      2A/2B VWD. The optimal VWF:CB/VWF:Ag ratio at which optimal discrimination
      occurred also differed between assays, with some improvements observed with some
      (but not all) assays following a harmonisation process that aimed to correct for
      different calibrator effects. Assay variability also compromised assay utility in
      some test occasions. Future standardisation and improvements in some commercial
      VWF:CB assays are needed before the VWF:CB assay can be more fully and globally
      utilised for discrimination of VWD types in diagnostic laboratories.

PMID- 20806124
TI  - Venous thromboembolism, age and hospitalisation: A potentially deadly
      combination.

PMID- 20806125
TI  - Haemostatic safety of a unique recombinant plasmin molecule lacking kringles 2-5.
AB  - We previously demonstrated a significant margin of haemostatic safety for full
      length plasmin in comparison with tissue plasminogen activator (t-PA). We now
      report studies that compare haemostatic safety of full-length plasmin with a
      novel recombinant plasmin derivative, (Delta K2-5) plasmin, consisting of kringle
      1 linked to the serine protease domain of plasmin. Agent was administered
      intravenously in a randomised, blinded manner in a rabbit model of fibrinolytic
      haemorrhage. A dose-related decrease in alpha2-antiplasmin, factor VIII, and
      fibrinogen followed administration of 1.8, 2.7, 3.7 and 4.6 mg/kg of (Delta K2-5)
      plasmin, with nadir fibrinogen concentrations of 65%, 40%, 30%, and 0% of initial
      levels, respectively. Mean primary bleeding time was undisturbed at 1.8 mg/kg
      (2.2 +/- 0.7 minutes), minimally prolonged at 2.7 or 3.7 mg/kg (5 +/- 2.9 and 4.4
      +/- 2.2 minutes), and prolonged at the purposefully toxic 4.6 mg/kg dose (12.8 +/
      18.8 minutes). Equimolar amounts of (Delta K2-5) plasmin and full-length plasmin
      had equal in vitro clot lysis efficacy, but in the bleeding model, (Delta K2-5)
      plasmin showed better haemostatic competency than full-length plasmin. This
      safety advantage may be explained by higher residual amounts of plasma fibrinogen
      in animals given (Delta K2-5) plasmin rather than full-length plasmin. We
      demonstrate that a unique recombinant plasmin mutant, (Delta K2-5) plasmin,
      possesses an advantage in hemostatic safety over an equimolar amount of full
      length plasmin.

PMID- 20806127
TI  - Non-parallelism in the one-stage coagulation factor assay is a phenomenon of
      lupus anticoagulants and not of individual factor inhibitors.

PMID- 20806126
TI  - Evaluation of AR-H067637, the active metabolite of the new direct thrombin
      inhibitor AZD0837, in models of venous and arterial thrombosis and bleeding in
      anaesthetised rats.
AB  - AZD0837, currently in clinical development, is a once-daily oral anticoagulant
      that is bioconverted to AR-H067637, a selective, reversible direct thrombin
      inhibitor (DTI). When developing a new DTI, the antithrombotic effects are
      commonly investigated in in vivo animal models; this report shows the effect of
      AR-H067637 in venous and arterial thrombosis and bleeding models in anaesthetised
      rats. Thrombus formation was induced by topical application of ferric chloride to
      the carotid artery or to the caval vein with partial stasis. Cutaneous incision
      bleeding time and muscle transection blood loss were assessed, with or without
      acetylsalicylic acid (ASA). Activated partial thromboplastin time (APTT), ecarin
      coagulation time (ECT) and thrombin coagulation time (TCT) were used as plasma
      biomarkers of anticoagulant effect. Dalteparin was used as a reference compound.
      AR-H067637, given by continuous infusion, displayed a dose-dependent
      antithrombotic effect, with 50% inhibition (IC50) of thrombus size in venous and
      arterial thrombosis models obtained at plasma concentrations of 0.13 MUM and 0.55
      MUM, respectively, without increased bleeding. Dose-dependent increased bleeding
      and blood loss were seen at plasma concentrations >=1 MUM AR-H067637. At the
      highest AR-H067637 plasma concentration tested, bleeding time and blood loss
      increased two and four times the vehicle group. Addition of ASA moderately
      potentiated bleeding time and blood loss. APTT, ECT and TCT were dose-dependently
      prolonged. These studies demonstrate that the DTI AR-H067637 inhibits thrombus
      formation in rat venous and arterial thrombosis models with no or minor increases
      in bleeding.

PMID- 20806128
TI  - [Perioperative nutrition medicine - right after surgery a schnitzel].

PMID- 20806129
TI  - [Legal opinion after erroneous total thyroidectomy reoperation].

PMID- 20806130
TI  - [Colorectal surgery marches onward].

PMID- 20806132
TI  - [Individualised and differentiated treatment of rectovaginal fistula].
AB  - Rectovaginal fistuale (RVF) are a serious and disabling problem for the patients
      and a surgical challenge for the treating physicians. The most common causes of
      RVF are postoperative complications, inflammatory bowel disease, complications of
      radiotherapy, obstetric complications, and neoplasia. Therapeutic options are
      diverse and results often unsatisfactory. This article presents the treatment of
      patients with rectovaginal fistulae in the general surgery department of
      University Hospital in Duesseldorf, Germany. The therapeutic strategy for
      treatment of RVF is divided according to aetiology, localisation, and
      comorbidity. A diverting ileostomy is particularly useful if acute inflammation
      exists. Secondary repair may then be a better option. An initial approach with a
      local repair by preanal repair is justified in low RVF. For failures muscle flaps
      are promising.

PMID- 20806131
TI  - [The optimult study concept - selective neoadjuvant chemoradiation therapy based
      on preoperative MRI].
AB  - Optimal surgery for rectal cancer, i. e., total mesorectal excision in the middle
      and lower rectum reduces local recurrence substantially. Multi-modal therapy
      further improves the rate of local recurrence in advanced rectal cancer. In
      Germany neoadjuvant chemoradiation therapy is most frequently given for these
      tumours. However, clinical staging by endosonography, CT scan and / or MRI is
      unreliable, particulary as regards lymph node category, which entails
      overtreatment of a relevant number of patients secondary to overstaging. Thus, a
      subgroup of patients has to tolerate side effects and long-term sequelae of
      neoadjuvant therapy without having oncological benefit from this pretreatment. It
      is of note that the prognosis of patients with advanced rectal cancer depends not
      only on the T and N category but also on the free circumferential margin of the
      tumour as determined by pathological examination. In contrast to the T and N
      category, the latter may be predicted before treatment by pelvic MRI. While
      several case series demonstrated that low local recurrence rates are achieved in
      patients when preoperative MRI showed free circumferential margins, this concept
      was never tested in a randomised controlled trial. We, therefore, designed a two
      armed randomised study with patients who suffer from rectal cancer and who have 2
      mm or more free circumferential margins on their preoperative MRI. These patients
      are either operated without pretreatment (intervention arm) or receive
      neoadjuvant chemoradiation therapy with subsequent surgery (control arm). If
      local recurrence in the intervention arm is not inferior to the control arm, this
      study may form the basis for an individualised therapeutic concept for rectal
      cancer based on preoperative MRI. Potentially, chemoradiation therapy may be
      avoided in the future for patients who will have no oncological benefit from this
      treatment modality.

PMID- 20806133
TI  - [Right- and left-sided colonic cancer - different tumour entities].
AB  - PURPOSE: Colorectal cancer is one of the most common malignancies in the Western
      world. In the past two decades, a growing amount of data has been reported
      suggesting that carcinomas of the right and left colon should be considered as
      different tumour entities. The aim of this review is to present a detailed
      analysis of the current knowledge regarding differences between right- and left
      sided colon cancer and potential consequences for daily practice. METHODS: For
      this report all articles with relevant information on differences between right-
      and left-sided colon carcinoma found via Pubmed searches were analysed.
      Furthermore, findings of a previous study performed by our group were included.
      RESULTS: Patients with right-sided colon cancer are significantly older,
      predominantly women, with a higher rate of comorbidities. Most of the large
      epidemiological studies reported a continued rightward shift of colorectal
      cancer. Histopathologically, carcinoma of the right colon show a higher
      percentage of poorly differentiated, locally advanced tumours with a higher rate
      of mucinous carcinoma and different pattern of metastatic spread. Survival is
      significantly worse in patients with right-sided carcinomas. There are numerous
      genetic differences which account for the distinct carcinogenesis and biological
      behaviour. CONCLUSIONS: The numerous findings regarding differences between right
      and left-sided colon cancers should have an impact on colon cancer screening and
      therapy. Firstly, there are defined risk groups which should receive complete
      colonoscopy, particularly if they present with symptoms suspicious for colon
      carcinoma. Furthermore, location of the colon cancer should be considered before
      group stratification into genetic, clinical and especially chemotherapy trials. A
      more tailored approach to colon cancer treatment would be highly desirable if
      future trials further support the hypothesis of two distinct tumour entities.

PMID- 20806134
TI  - [Tumour stem cells and metastasis].
AB  - The underlying mechanisms of cancer development, invasion and metastasis are
      still only partly unraveled. Cancer stem cells (CSC) and the so-called epithelial
      mesenchymal transition (EMT) seem to contribute to these oncological phenomena.
      Cancer stem cells which, according to our present knowledge, play an important
      role in tumour development and persistence, are operationally defined. The
      embryonic programme of EMT is activated aberrantly in cancer cells at the
      invasive front and seems to contribute to tumour invasion and metastasis. Recent
      observations suggest that the EMT and CSC traits are closely related. This
      provides new explanatory models for cancer development and metastasis.

PMID- 20806135
TI  - [PDCA cyclus and morbidity and mortality conference as a basic tool for reduction
      of wound infection in colorectal surgery].
AB  - BACKGROUND: Morbidity and mortality conferences (M + M) are used for the
      discussion of errors and thereby further education in surgery. However, it is not
      clear whether this kind of quality assurance has any influence on the results of
      surgery. MATERIAL AND METHODS: We investigated whether M + M as part of PDCA
      cylce (plan, do, check, act) with prospectively collected quality data, fixing
      future goals using benchmarking data and defining a strategy to reach these goals
      can lead to an increase in quality. RESULTS: Using surveillance data n = 673
      colorectal resections were analysed. Between 2003 and 2008 we found a wound
      infection rate of 5.6 %. Comparing 2003-2005 (period of strategy development
      using M + M) and 2006-2008 (period of strategy conversion) the frequency
      decreased from 7.8 % to 3.5 % (p = 0.012). Thereby the risk factors for wound
      infection (ASA, wound classification, duration of surgery and wound infection
      score) were not different. CONCLUSIONS: M + M as part of this PDCA cycle resulted
      in a clear increase in surgical quality.

PMID- 20806136
TI  - [Diagnosis of acute appendicitis over two decades - effects of increasing number
      of imaging procedures on costs, preoperative reliability and patient outcome].
AB  - BACKGROUND: An increasing number of modern imaging procedures are being applied
      for the diagnosis of appendicitis. We compared one hundred consecutive
      appendectomies of the years 1988, 1998 and 2008 concerning reliability of
      preoperative diagnosis and resulting costs. METHODS: We analysed the first one
      hundred consecutive patients undergoing appendectomy during the years 1988, 1998
      and 2008, 59 % were female and 41 % male. The average age was 26 years, the
      average BMI 21.09. The costs and results of radiological investigations (US, CT,
      MRI, X-ray) have been compared in all patients. The sensitivity of ultrasound and
      CT scan in preoperative diagnosis has been analysed. RESULTS: The number of
      preoperative imaging procedures for the diagnosis of appendicitis has increased
      over the last two decades. Simultaneously increased the costs (total costs and
      costs per partient) for imaging procedures. 2008 the costs were 10 times higher
      than 1988. CT had a higher sensitivity (77 %) in the diagnosis of appendicitis
      than ultrasound (33 %). The number of operations because of subacute and chronic
      appendicitis was lower in 2008 (34 of 100) compared with 1988 (80 of 100) and
      1998 (60 of 100). In 2008 (14) we found a higher number of gangrenous and
      perforated appendicitis compared to 1988 (2) and 1998 (5). The majority (50 of
      100) of patients in the group with acute and phlegmonous appendicitis was found
      in 2008. CONCLUSION: There has been an increase in the use of preoperative
      imaging procedures in the diagnosis of appendicitis during the last 20 years.
      This causes more costs in the public health system. Ultrasound as the standard
      imaging method for diagnosing appendicitis showed poor sensitivity. CT scans had
      good results concerning sensitivity, but are expensive and involve exposure to
      radiation for the patient.

PMID- 20806137
TI  - [Faecothorax].

PMID- 20806138
TI  - [Isolated ileal perforation after blunt abdominal trauma].
AB  - Perforating injuries to the small bowel due to a blunt abdominal trauma are rare.
      Especially in the case of an isolated injury where diagnostic investigations have
      failed, it may result in delayed therapy and a prolonged clinical course. Here,
      we report on an isolated ileal perforation caused by a blunt abdominal trauma in
      setting of a domestic accident.

PMID- 20806139
TI  - [Cerebral vasculitis as rare extraintestinal manifestation in ulcerative colitis:
      review of the literature and case report].

PMID- 20806140
TI  - [Coincidence of symptomatic infrarenal abdominal aortic aneurysm and haemorrhagic
      tumour of the ileocecal region].

PMID- 20806141
TI  - [Surgically relevant venous diseases and stage-adapted conservative therapy -
      main topic of the latest Berlin symposium of vascular surgery].

PMID- 20806142
TI  - [Spinal cord stimulation - evidence and personal experience].
AB  - Spinal cord stimulation (SCS) has been successfully used to treat chronic pain
      syndromes for decades. For this purpose, an electrode is implanted into the
      epidural space under local anaesthesia and connected to a neurostimulator which
      applies a weak direct current to the dorsal roots of the spinal column. Besides
      pain control, SCS increases the blood supply in the stimulated area. This effect
      is mediated by a sympathicolytic effect and the liberation of vasodilatators
      within the stimulated skin area. A Cochrane meta-analysis has revealed a
      significantly increased limb salvage rate in patients with non-reconstructable
      critical limb ischaemia (CLI) treated with SCS. The effect of SCS in CLI might be
      predicted by the measurement of forefoot transcutaneous pO (2) in supine and
      dependent positions, which renders trial stimulation unnecessary in many cases.

PMID- 20806143
TI  - [The popliteal artery aneurysm - surgical and endovascular therapy].
AB  - Popliteal artery aneurysm is defined as an enlargement of the popliteal artery of
      more than 50 % of the original diameter. In more than 95 % of the cases,
      arteriosclerosis is the cause. The prevalence of asymptomatic and symptomatic
      popliteal artery aneurysms is less than 0.5 % of the population but rises in the
      age group of the 65-80-year-olds up to 1 %. About one-third of all diagnosed
      popliteal artery aneurysms are asymptomatic incidental findings, whereas the
      other two-thirds are noticed due to their symptoms (acute or chronic ischaemia,
      local compression syndrome, rupture). The indication for invasive treatment is
      considered for asymptomatic popliteal artery aneurysms at a diameter of more than
      2 cm. Symptomatic popliteal artery aneurysms are always an indication for
      treatment, but acute and chronic ischaemia is associated with a high morbidity.
      Since the middle of the last century surgical techniques have been used in the
      therapy for popliteal artery aneurysms and represent the gold standard in
      treatment strategies. Nevertheless, a growing number of reports about
      endovascular interventions for popliteal artery aneurysms are being published. In
      this review the state of knowledge about indications, applicability and results
      of invasive therapies for the treatment of popliteal artery aneurysms are
      presented.

PMID- 20806144
TI  - [Cystic adventitial disease (CAD) of the popliteal artery].

PMID- 20806147
TI  - [Chances and risks of perinatal medicine--the future of obstetrics in Germany].

PMID- 20806145
TI  - [A rare aneurysm of the popliteal vein].
AB  - BACKGROUND: A popliteal venous aneurysm is rare but needs to be considered a
      silent threat due to the risk of pulmonary embolism. CASE REPORT AND METHOD:
      Using the report of an exemplary case, the diagnostic and therapeutic management
      including outcome is described. In particular, the favourable, case-adapted
      surgical approach of aneurysma resection and direct suture of the vascular wall
      because of the extraordinary aneurysma of the right popliteal vein is emphasised.
      RESULTS AND CLINICAL COURSE: A 50-year-old woman underwent duplex ultrasonography
      because of pain in the right popliteal fossa, which revealed an aneurysm of the
      popliteal vein. The diagnosis was confirmed by phlebography. During the surgical
      approach, the popliteal vein was explored and the aneurysm subsequently excised.
      The defect in the wall of the popliteal vein was directly sutured avoiding a
      stenotic segment of the vein. The postoperative course was uneventful.
      Postoperatively, oral anticoagulation with coumarins was initiated for 6 months;
      follow-up investigations using duplex ultrasonography at 6 and 12 months showed a
      patent popliteal vein with no thrombotic changes. CONCLUSION: According to the
      recommendations from the international literature, surgical approach using
      venorrhaphy or resection is absolutely indicated to prevent pulmonary embolism,
      especially in the mostly younger patients.

PMID- 20806148
TI  - [Congenital gastroschisis--prenatal diagnosis and perinatal management].
AB  - The birth prevalence of gastroschisis is increasing world-wide. This situation
      applies particularly to young, slim women who smoke. At a first glance this is a
      paradox in light of the ever-increasing age of pregnant women among whom there
      are fewer and fewer smokers. In numerous studies it has been clearly demonstrated
      that not only (nutritional) teratogenic substances and environmental factors but
      also epidemiological causes can be held responsible for this phenomenon. Nowadays
      gastroschisis is detected prenatally in up to 90% of all foetuses. Advantages of
      a prenatal diagnosis include the identification of associated disorders and the
      determination of a high-risk constellation (IUGR, intraabdominal bowel dilatation
      or vanishing gut). This is essential for an adequate interdisciplinary counseling
      for the afflicted parents together with obstetricians, paediatric surgeons and
      neonatalogists. The efficacy of serial amnioexchanges with regard to a better
      neonatal outcome has as yet not been unambiguously clarified. The possibilities
      for surgical procedures on the foetus are limited and can at present only be
      considered as experimental attempts in animal models. From an obstetrical
      perspective the in utero transport and elective Caesarean section before
      completion of the 36 (th) week of gestation in a tertiary centre with appropriate
      facilities (paediatric surgery, neonatalogy) seem to be the course recommended by
      most authors in spite of inconclusive data. The survival rates for babies with
      gastroschisis after operative treatment (primary defect closure, silotechnique)
      are considerably high (>90%).

PMID- 20806149
TI  - [Patient-controlled intravenous analgesia with remifentanil as an alternative to
      epidural analgesia during labor: case series and discussion of medicolegal
      aspects].
AB  - BACKGROUND: Epidural analgesia is considered as the standard method for labor
      analgesia by inducing a minimal negative impact on labor while providing
      effective analgesia. Labor analgesia in the absence of epidural analgesia is
      difficult to achieve with the commonly used analgesic interventions. If epidural
      analgesia is not feasible due to coagulation disorders, anticoagulation,
      inability to insert an epidural catheter or due to the mother''s refusal to
      accept neuraxial analgesia, there is a need for interventions to cope with labor
      pain. So far, pethidine, diamorphine, meptazinol and spasmolytics remain the most
      widely used substances for IM and IV use. Unfortunately, in addition to not being
      very effective, these interventions may be associated with undesirable side
      effects for the parturient and the newborn. For a decade, anaesthesiologists have
      experienced the unique properties of remifentanil in the settings of surgical
      anaesthesia and conscious sedation since it was introduced for labor analgesia.
      Unfortunately, remifentanil is not licensed for administration to the pregnant
      patient, and it is unlikely that the manufacturers would consider the cost
      justified. METHODS: Therefore, relevant concerns, legal issues and precautions
      are discussed based on the presentation of case series and a protocol is
      presented on how the use of remifentanil can be safely implemented for labor
      analgesia in selected situations. RESULTS AND CONCLUSIONS: Proper informed
      consent, appropriate monitoring for the mother and the newborn, one-to-one
      nursing or midwifery care as well as the availability of an attending physician
      experienced in neonatal resuscitation and an anaesthesiologist with experience
      regarding the use of remifentanil are important to ensure that this method
      retains its good reputation for obstetric analgesia.

PMID- 20806150
TI  - [How to define a non-reassuring FHR tracing online].
AB  - BACKGROUND: Sub partu foetal heart-rate (FHR) patterns are difficult to evaluate.
      Until now we have no numerical criteria to reliably define what is a non
      reassuring or even a 'pathological' FHR tracing. Computer-aided FHR analysis
      using the new WAS score offers the unique opportunity to assess numerical
      boundaries for these definitions. METHODS: Direct FHR tracings of 475 foetuses,
      all delivered by the vaginal route, were recorded electronically and the last 30
      min of each tracing were used for computation of the WAS score. The WAS score
      refers to FHR frequency, microfluctuation, and oscillation amplitude per minute.
      Acid-base and blood-gas analyses were performed in blood of the umbilical artery
      (UA) and vein (UV) immediately post partum. pH (UA) and the WAS score were
      correlated (r) and the 4 variables sensitivity, specificity, the false positive
      rate (FPR) and the false negative rate (FNR) were determined. ROC plots for
      different threshold pH (UA) values were performed. RESULTS: pH (UA) and the WAS
      score are normally distributed: mean pH (UA)=7.263+/-0.064 and mean WAS score
      2.78+/-0.81, respectively. The correlation coefficient, r amounts to 0.657,
      P<<10(-4). Using the mean pH (UA) and the mean WAS score leads to a sensitivity
      and specificity both of 72% with an FPR and FNR both of 28%. Using a WAS score of
      1.816 and the threshold pH (UA) of 7.122 sensitivity becomes the first time 100%
      (FNR=0%) and FPR decreases to 10.7%. These 2 values are chosen to separate a
      normal (score >1.816) from an abnormal (non-reassuring) CTG (score < or =1.816).
      According to this definition newborns with a reassuring (normal) FHR tracing
      (N=417) have a pH (UA)=7.275+/-0.055, pCO (2)=52.3+/-7.9, BE (Ecf,oxy.)=-3.0+/
      2.3, sO (2)=24.9+/-12.3 with an acidotic risk (pH (UA) <7.100) of 0% and APGAR 1
      min <7=0.96%, respectively. Neonates with an abnormal (non-reassuring) FHR
      tracing (N=58) present a mean pH (UA)=7.178+/-0.066, pCO (2)=62.6+/-9.6, BE
      (Ecf,oxy.)=-5.4+/-2.6, sO (2)=18.3+/-12.0 and an acidotic risk of 6.9%. No
      neonate in this group was severely depressed (APGAR 1 min < or =3). Separation of
      the true positive (pH (UA) <7.122) from the false positive (pH (UA) > or =7.122)
      cases yields 10 babies with a mean pH (UA)=7.084+/-0.053, pCO (2)=71.8+/-10.7, BE
      (Ecf,oxy.)=-8.4+/-2.0, sO (2)=20.2+/-14.5 and an acidotic risk of 44.4%; in this
      group also not one baby was severely depressed (APGAR 1 min < or =3) but 3 were
      already moderately affected (<7 after 1 min). No infant scored <7 after 5 min.
      There must be a lower limit for the definition of a true 'pathological' FHR
      tracing; this boundary should not be identical with the threshold pH value where
      hypoxic injuries in term infants usually commence. For FHF this is a WAS score of
      0.630 and a threshold pH (UA) of 7.075. CONCLUSION: Using sensitivity,
      specificity, FPR and FNR of the FHR sub partu, it is possible to discriminate
      online a normal (reassuring) from an abnormal (non-reassuring) FHR tracing by a
      simple computer-aided procedure which we call WAS scoring.

PMID- 20806151
TI  - Age-specific preterm birth rates after exclusion of risk factors--an analysis of
      the german perinatal survey.
AB  - AIM: A description of preterm birth rates - specified according to maternal age -
      after the exclusion of anamnestic risk factors. MATERIAL AND METHODS: Data for
      this study were taken from the German Perinatal Survey of 1998-2000. We analysed
      data from 492,576 singleton pregnancies and determined preterm birth rates
      according to maternal age after a stepwise exclusion of anamnestic risk factors.
      RESULTS: There was a U-shaped dependence of preterm birth rates on maternal age.
      The lowest preterm birth rate (without excluding women with anamnestic risk
      factors) was 5.6% at a maternal age of 29 years. The prevalence of some
      anamnestic risk factors for preterm birth, such as previous stillbirths,
      spontaneous and induced abortions, and ectopic pregnancies, increased with
      maternal age. Excluding women with anamnestic risk factors lowered the preterm
      birth rates substantially. The lowest preterm birth rates were found in women
      with one previous live birth, without any anamnestic risk factors, and with a
      body mass index (BMI) of 25.00-29.99. With these restrictions, we found preterm
      birth rates of under 2% for women aged 24-31 years. CONCLUSIONS: The magnitude
      and age-dependence of the preterm birth rate can to some extent be explained with
      the age-dependent prevalence of anamnestic risk factors for preterm birth.
      Excluding women with anamnestic risk factors from our study population lowered
      the preterm birth rates substantially.

PMID- 20806152
TI  - [Foetal rhabdomyosarcoma with massive cardiac and placental infiltration
      associated with intrauterine foetal death].
AB  - Rhabdomyosarcoma is a common malignant soft-tissue tumour in children, accounting
      for 6-7% of all malignant tumours in childhood. Congenital neoplasms are very
      rare in childhood and represent 2.5% of all paediatric tumours; the intrauterine
      or congenital diagnosis of rhabdomyosarcomas is extremely seldom. The most
      frequent locations of rhabdomyosarcomas are the head and neck regions. There are
      a number of ultrasonographic differential diagnoses. In cases of foetal
      rhabdomyosarcomas in utero, not only distant metastases but also the possibility
      of placental infiltration and thus of hypothetical distant metastases in the
      mother must be taken into consideration because of their metastatic potential.
      Only very few cases of transplacental penetration of tumour cells and especially
      of foeto-maternal metastatic invasion, in contrast to materno-foetal tumour cell
      transfer in the case of maternal cancer disease, have been reported in the
      literature. We report on a foetal rhabdomyosarcoma of the head and neck area with
      massive cardiac and placental infiltration associated with intrauterine foetal
      death in the second trimester. Sonographic features and necropsy findings are
      described and the differential diagnosis is discussed. Furthermore, diagnostic
      approaches to rule out a pattern of transplacental metastases are presented.

PMID- 20806153
TI  - Drainage of esophageal leakage using endoscopic vacuum therapy: a prospective
      pilot study.
AB  - BACKGROUND AND STUDY AIMS: Major leakage from an esophageal anastomosis is a life
      threatening surgical complication. Endoscopically guided endoluminal vacuum
      therapy using polyurethane sponges is a new method for treating such leakage.
      PATIENTS AND METHODS: Between June 2007 and June 2009, five patients (mean age 68
      years) who developed anastomotic leakage after esophageal surgery were
      prospectively evaluated. After endoscopic diagnosis of a major leakage,
      polyurethane sponges were endoscopically positioned in the wound cavity of the
      anastomosis. Continuous suction was applied via drainage tubes fixed to the
      sponges. Initially sponges were endoscopically changed three times per week.
      RESULTS: In all five patients treatment was successful. Median time to reduce
      levels of inflammation markers by 50 % was 10 days for white blood cell (WBC)
      count and 7 days for C-reactive protein (CRP). The smallest initial wound cavity
      size was 42 cm (3) and the largest was 157 cm (3). The median duration of
      drainage was 28 days, with a median of 9 sponge changes and a median time to
      total cavity closure of 42 days. Two patients needed anastomotic dilation by
      Savary-Miller bougienage due to stenosis found on further follow-up. One of these
      patients died of acute severe hemorrhage from an aortoanastomotic fistula after
      the dilation procedure. CONCLUSIONS: Endoscopically assisted vacuum therapy is a
      well-tolerated and effective therapeutic option for treatment of major esophageal
      leaks after surgery. Additional surgery was avoided in all cases. However, the
      occurrence of a delayed aortoesophageal fistula calls for careful further
      investigation of this new technique.

PMID- 20806154
TI  - Interobserver reliability in the endoscopic diagnosis and grading of Barrett's
      esophagus: an Asian multinational study.
AB  - BACKGROUND AND STUDY AIM: The establishment of precise and valid diagnostic
      criteria is important for any disease. We determined the interobserver
      reliability in the endoscopic diagnosis and grading of Barrett's esophagus.
      PATIENTS AND METHODS: Video clips of endoscopy in 21 patients with/without
      Barrett's esophagus were used for training (n = 3) and for diagnosis/grading (n =
      18) of Barrett's esophagus by endoscopists from seven hospitals in Asia.
      Barrett's esophagus was graded using the Prague C & M Criteria whereby the
      circumferential extent of the Barrett's segment (C value), maximum extent of
      Barrett's segment (M value), location of the gastroesophageal junction, and
      location of the diaphragmatic hiatus were scored. The intraclass correlation
      coefficients (ICC) were calculated as a measure of interobserver reliability.
      RESULTS: A total of 34 endoscopists participated. ICC values for the scores of
      the C value, M value, location of the gastroesophageal junction, and location of
      the diaphragmatic hiatus were: 0.92 (95 % confidence interval [CI] 0.88 - 0.97),
      0.94 (95 %CI 0.90 - 0.98), 0.86 (95 %CI 0.78 - 0.94), and 0.81 (95 %CI 0.71 -
      0.92), respectively, indicating excellent interobserver agreement. The
      differences in region/country, endoscopists' experience, case volume of
      participating centers, or primary practice type had no significant effect on the
      reliability. The ICC values for recognition of Barrett's esophagus of > or = 1 cm
      were 0.90 (95 %CI 0.80 - 1.00) and 0.92 (95 %CI 0.87 - 0.98) for the C and M
      values, respectively, whereas the corresponding ICC values for Barrett's segment
      of < 1 cm were 0.18 (95 %CI 0.03 - 0.32) and 0.21 (95 %CI 0.00 - 0.51),
      respectively. CONCLUSIONS: Despite the uncommon occurrence of Barrett's esophagus
      in Asia, our endoscopists exhibited excellent agreement in the endoscopic
      diagnosis and grading of Barrett's esophagus using the Prague C & M Criteria.
      However, in view of the low interobserver reliability in recognizing Barrett's
      segments of < 1 cm, future studies in Asia should take this into account when
      selecting the study population.

PMID- 20806155
TI  - Retrospective study of technical aspects and complications of endoscopic
      submucosal dissection for laterally spreading tumors of the colorectum.
AB  - BACKGROUND AND STUDY AIMS: Laterally spreading tumors - non granular type (LST
      NG) are more often considered candidates for endoscopic submucosal dissection
      (ESD) than laterally spreading tumors - granular type (LST-G), because of their
      higher potential for submucosal invasion. However, ESD for LST-NG can be
      technically difficult. The aim of our study was to compare our ESD results for
      LST-NG and for LST-G. PATIENTS AND METHODS: Ninety-nine LST-NG and 169 LST-G
      measuring 20 mm in size or more were removed by ESD. We retrospectively evaluated
      the clinicopathological features of the tumors and treatment results (en bloc
      resection rate, procedure time and speed, rate of use of ancillary devices, and
      complication and recurrence rates). RESULTS: Histopathology revealed that there
      were more submucosally invasive lesions in the LST-NG than in the LST-G group (28
      % vs. 9 %; P < 0.0001). The en bloc resection rate, en bloc R0 resection rate,
      and en bloc curative resection rate of LST-NG were similar to those of LST-G (LST
      NG: 99 %, 98 %, and 88 %; LST-G: 99 %, 98 %, and 91 %). In LST-NG, the median
      procedure time tended to be longer (LST-NG: 69 min; LST-G: 60 min) and the median
      procedure speed was slower (LST-NG: 0.15 cm (2)/min; LST-G: 0.25 cm (2)/min; P <
      0.0001). Use of ancillary devices was higher for LST-NG (38 % vs. 15 % for LST-G;
      P < 0.0001), as was the perforation rate (5.1 % vs. 0.6 % for LST-G; P = 0.027).
      No recurrence was seen in either group. CONCLUSIONS: ESD was an effective
      treatment method for both LST-NG and LST-G. However, the degree of technical
      difficulty appears higher for LST-NG than for LST-G lesions, as shown by the
      lower dissection speed and higher perforation rate. ESD for LST-NG should
      probably be performed by those with significant experience of colorectal ESD.

PMID- 20806156
TI  - Long-term outcomes of endoscopic submucosal dissection for colorectal epithelial
      neoplasms.
AB  - BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) provides a high en
      bloc resection rate with less invasiveness than surgical resection for large or
      scarring gastrointestinal neoplasms. However, detailed outcomes in colorectal ESD
      are still lacking. The aim of our study was to elucidate short- and long-term
      outcomes of colorectal ESD. PATIENTS AND METHODS: 310 consecutive colorectal
      epithelial neoplasms (146 adenomas, 164 carcinomas), in 290 patients, which
      fulfilled our indication criteria and were treated with ESD between July 2000 and
      December 2008 were studied. ESD was done by three skilled endoscopists. As short
      term outcomes, rates of en bloc resection, en bloc plus R0 resection, and major
      complications were analyzed. As long-term outcomes, disease-free and overall
      survival were assessed in 224 patients. RESULTS: Rates of en bloc resection and
      en bloc plus R0 resection were 90.3 % and 74.5 %, respectively. Eight patients
      underwent additional colectomy due to histopathologically proven possible node
      positive cancer. Intraoperative perforations occurred with 14 lesions (4.5 %),
      which were treated successfully only by endoscopic clipping. Emergent surgery was
      needed for one case of postoperative perforation. Blood transfusion due to
      intraoperative massive bleeding was required in 1 case (0.3 %). Postoperative
      bleeding occurred with four lesions (1.3 %), and was endoscopically managed
      without blood transfusion. Local recurrence was detected in 4 lesions (4/202
      patients, 2.0 %); resection had been piecemeal in all 4. During a median follow
      up of 38.7 months (range 12.8 - 104.2), the 3- and 5-year overall/disease
      specific survivals were 97.1/100 % and 95.3/100 %, respectively. CONCLUSIONS:
      Colorectal ESD showed favorable long-term outcomes. It may largely replace
      colectomy for node-negative colorectal epithelial neoplasia.

PMID- 20806157
TI  - Air suctioning during colon biopsy forceps removal reduces bacterial air
      contamination in the endoscopy suite.
AB  - BACKGROUND AND STUDY AIMS: Bacterial contamination of endoscopy suites is of
      concern; however studies evaluating bacterial aerosols are lacking. We aimed to
      determine the effectiveness of air suctioning during removal of biopsy forceps in
      reducing bacterial air contamination. PATIENTS AND METHODS: This was a
      prospective single-blinded trial involving 50 patients who were undergoing
      elective nontherapeutic colonoscopy. During colonoscopy, endoscopists removed the
      biopsy forceps first without and then with suctioning following contact with the
      sigmoid mucosa. A total of 50 L of air was collected continuously for 30 seconds
      at 30-cm distance from the biopsy channel valve of the colonoscope, with time
      starting at forceps removal. Airborne bacteria were collected by an impactor air
      sampler (MAS-100). Standard Petri dishes with CNA blood agar were used to culture
      Gram-positive bacteria. Main outcome measure was the bacterial load in endoscopy
      room air. RESULTS: At the beginning and end of the daily colonoscopy program, the
      median (and interquartile [IQR] range) bioaerosol burden was 4 colony forming
      units (CFU)/m (3) (IQR 3 - 6) and 16 CFU/m (3) (IQR 13 - 18), respectively. Air
      suctioning during removal of the biopsy forceps reduced the bioaerosol burden
      from a median of 14 CFU/m (3) (IQR 11 - 29) to a median of 7 CFU/m (3) (IQR 4 -
      16) ( P = 0.0001). Predominantly enterococci were identified on the agar plates.
      CONCLUSION: The bacterial aerosol burden during handling of biopsy forceps can be
      reduced by applying air suction while removing the forceps. This simple method
      may reduce transmission of infectious agents during gastrointestinal endoscopies.

PMID- 20806158
TI  - Esophageal leaks: extending our toolbox?

PMID- 20806159
TI  - Bacterial aerosols during colonoscopy: something to be worried about?

PMID- 20806160
TI  - Endoscopic closure of postoperative esophageal leaks with a novel over-the-scope
      clip system.
AB  - Management of esophageal anastomotic leaks is associated with high morbidity and
      mortality and remains an interdisciplinary challenge. We describe the first two
      cases of endoscopic closure of postoperative leaks following gastrectomy and
      primary repair after spontaneous acute esophageal perforation, using the over-the
      scope clip (OTSC) system (Ovesco Endoscopy GmbH, Tubingen, Germany). Both leaks
      were successfully sealed with one clip. While one patient recovered without
      reintervention, in the other patient the postoperative leak reappeared following
      clip displacement 13 days later.

PMID- 20806161
TI  - Safety of single-balloon enteroscopy: our experience of 72 procedures.

PMID- 20806164
TI  - The PAN study: the first step into the future.

PMID- 20806165
TI  - [Should probiotics already be recommended as standard clinical care for preterm
      infants with birth weights below 1,500 g?].

PMID- 20806166
TI  - Neurodevelopmental outcome following congenital cytomegalovirus infection in
      preterm infants with twin-to-twin transfusion syndrome: a case report.
AB  - Twin-to-twin transfusion syndrome and conital cytomegalovirus infection bear the
      risk of brain damage. In the 27th week of gestation of a twin pregnancy a
      Caesarean section was performed because of pathological cardiotocogram and
      Doppler ultrasonography of the second twin (recipient). Both infants presented
      with severe, persistent thrombocytopenia, elevated liver enzymes and direct
      hyperbilirubinemia. Primary congenital CMV infection was diagnosed. Both twins
      showed severe neuropathological symptoms, pathological aEEG with seizure activity
      and severe neurodevelopmental delay at corrected age of 12 months. The severity
      of brain pathology, the complex etiology, its consequence for neurotion with
      extreme prematurity make this case of special interest.

PMID- 20806167
TI  - Efficacy of carboplatin plus vincristine in an optic pathway glioma.

PMID- 20806168
TI  - Recurrent fever episodes with arthralgia or hyperesthesia--have you ruled out
      parvovirus B19?

PMID- 20806169
TI  - Can norovirus infection lead to a postinfectious arthritis? Report of 2 possible
      cases.

PMID- 20806170
TI  - [Commentary on the article of S. Low et al.: Intra- and interobserver reliability
      of digitally photodocumented findings in wrist arthroscopy].

PMID- 20806172
TI  - [Early diagnosis of skin cancer].
AB  - The skin is the most affected organ by cancer. The incidence rates of skin cancer
      are steadily increasing, both for melanoma and non-melanoma skin cancers
      (squamous cell carcinoma, basal cell carcinoma). Over 90 % of the death cases
      from skin cancers attribute to melanoma. Survival from melanoma is strongly
      related to tumour thickness. Therefore early detection is the most important step
      to improve prognosis. In the last years a number of new non invasive techniques
      for the early diagnosis of melanoma have been developed which are superior to the
      naked eye examination. In this overview article we present some non-invasive
      diagnostic techniques like total body photography, digital dermoscopy and
      confocal microscopy which in addition to dermoscopy assist the dermatologist in
      differentiating nevi from early melanomas.Non-melanoma skin cancer can be
      prevented by accurate sun protection. Early squamous cell carcinomas and basal
      cell carcinomas can be treated either invasively or non-invasively with excellent
      prognosis.

PMID- 20806173
TI  - [Current therapy of carcinoma of the skin].
AB  - Interferon alpha as adjuvant therapy in high risk melanoma delays relapses and
      distant metastasis as shown in large clinical trials and meta-analysis. There are
      clear signs that a long term low dose interferon therapy is especially effective
      in patients with micrometastasis (detected by sentinel node biopsy).Patient with
      stage IV melanoma (distant metastasis) need systemic therapy in most cases. Since
      until today there is no treatment that has been proven to prolong the overall
      survival for this patient population. We recommend according international
      guidelines that these patients are treated in the context of clinical trials in a
      melanoma reference center.

PMID- 20806174
TI  - [Cutaneous lymphomas].
AB  - Cutaneous lymphomas are a heterogenous group of lymphoproliferative disorders of
      the T- and B-lymphocytes with a low incidence of approximately 1:100000/year.
      They belong to the Non-Hodgkin lymphoma. The skin is the second most abundant
      site of extranodal lymphoma formation (after the GI tract). The new WHO/EORTC
      classification of cutaneous T- and B-cell lymphomas provides a widely accepted
      nomenclature for primary cutaneous lymphomas based primarily on clinical, but
      also on histologic, cytologic and molecular features. It has already proven to be
      an invaluable tool for international prospective clinical studies. The clear
      distinction of primary cutaneous from secondary cutaneous lymphoma will also be
      important to prevent overtreatment of the frequently benign primary cutaneous
      lymphoma. Treatment of primary cutaneous lymphoma is skin-directed in early
      disease stages, and uses as systemic approach in advanced stages. Skin-directed
      therapies encompass UV-light treatment such as UVB311nm, or PUVA, topical
      steroids class III and IV, or bexaroten gel. Systemic treatment options may be
      immunomodulatory, such as treatment with interferon alpha injection, or biologic
      response modifiers such as bexarotene. We recommend that advanced stages of
      cutaneous lymphoma should be treated in centers that offer clinical studies in
      this field, because prognosis of late stages is still dismal and there is so far
      no therapeutic approach that has led to an increase in overall survival. Hence,
      inclusion of patients in prospective controlled clinical studies should always be
      considered in patients with primary cutaneous lymphoma.

PMID- 20806175
TI  - [Autoimmune bullous skin disorders].
AB  - Autoimmune bullous skin disorders are rare, potentially fatal disorders of skin
      and mucous membranes which are associated with IgG or IgA autoantibodies against
      distinct adhesion molecules of the epidermis and dermal epidermal basement
      membrane zone, respectively. These autoantibodies lead to a loss of skin adhesion
      which shows up clinically as the formation of blisters or erosions. In pemphigus,
      loss of adhesion occurs within the epidermis while in the pemphigoids, linear IgA
      dermatosis, epidermolysis bullosa acquisita and dermatitis herpetiformis, loss of
      adhesion takes place within or underneath the basement membrane zone. The
      autoantigens of these disorders are largely identified and characterized. Making
      the diagnosis of autoimmune bullous skin diseases is based on histology and
      direct immunofluorescence of perilesional skin and the serological detection of
      autoantibodides by indirect immunofluorescence and recombinant autoantigens.
      Therapeutically, systemic treatment with glucocorticoids is combined with
      immunosuppressive adjuvants which allow for the fast reduction of systemic
      steroids. A prospective trial in pemphigus showed that adjuvant treatment with
      azathioprine, mycophenolate mofetil and cyclophosphamide, respectively, led to a
      significant reduction of the cummulative dose of systemic steroids until complete
      clinical remission was achieved. In bullous pemphigoid, topical treatment with
      clobetasol led to complete clinical remissions without major side effects seen
      when glucocorticoids were applied systemically. Therapeutic depletion of B cells
      by rituximab as a second line therapy has significantly improved the overall
      prognosis of pemphigus. Comparable controlled therapeutic trials have not yet
      been performed in dermatitis herpetiformis and epidermolysis bullosa acquisita.

PMID- 20806176
TI  - [Genodermatoses for practitioners--principles and concepts].
AB  - Every disease is a mirror of interactions between genes and the environment. In
      monogenic disorders only one mutation can lead to a specific phenotype. However
      the spectrum and the degree of manifestations depend on numerous factors from the
      environment. Ichthyosis vulgaris is caused by a mutation in the filaggrin gene.
      However the phenotype is much more pronounced in the winter months. In polygenic
      disorders such as atopic dermatitis numerous modifying genes influence the
      phenotype including a mutation in filaggrin. The skin is the organ of the human
      body which is most commonly involved in monogenic diseases. More than one third
      of all genetic diseases affect the integument. At the very moment more than 350
      genodermatoses are identified with functional insights. The Human Genome Project
      was finished in 2001 with the aim that all genes can be identified for
      diagnostics, pharmacogenomics potential gene therapy and to understand the
      principle basis of diseases. The next project called ENCODE for Enzyclopedia of
      DNA Elements targets to identify all functional elements in the human genome
      sequence. MicroRNAs seem to have great importance for the regulation of
      genefunctions in the skin. At the moment epigenetics is at the epicentre of
      modern medicine. Epigenetics is the study of non-DNA sequence-related heredity.
      Epigenetics is an important tool to study the relationship between the genome and
      the environment. In the second part cases will be presented and the way of
      diagnosis making will be shown. It will be shown that it is very important to
      find clinical key features which may allow an allocation to a genetic pathway.

PMID- 20806177
TI  - The differences in chromogranin A (CgA) concentrations measured in serum and in
      plasma by IRMA and ELISA methods.
AB  - INTRODUCTION: Chromogranin A (CgA) is regarded as a major, nonspecific marker of
      neuroendocrine tumors (NET). Its estimation appears helpful for diagnostic
      purposes and is particularly useful for monitoring the treatment of NET. It must
      be kept in mind, however, that various factors, drugs, or coexisting diseases may
      influence the outcome of CgA measurement in blood. One such analytical factor is
      the sort of studied biological material, whether it is plasma or serum. The aim
      of our study was to compare directly the results of CgA concentrations measured
      in serum and in plasma by IRMA and ELISA. MATERIAL AND METHODS: We analysed 122
      samples of EDTA-plasma and 122 samples of serum by IRMA method, 20 samples of
      EDTAplasma and 20 samples of serum by IRMA and ELISA, 25 heparinised-plasma
      samples and 25 samples of EDTA-plasma by IRMA and ELISA methods, and 8 EDTA
      plasma, heparinised-plasma, and serum samples by IRMA and ELISA. The material for
      comparative study was obtained during the same blood collection from the same
      subjects (volunteers and patients with NET). CgA was measured with the use of
      kits manufactured by CIS bio International (France). RESULTS: CgA concentrations
      were markedly higher in plasma than in serum. Using the IRMA method, the
      difference in the CgA range between 10-100 ng/mL approached 20-70% (median 61 v.
      42), in the range 101-300 ng/mL--12-60% (median 147 v. 101), and in the CgA range
      301-1076 ng/mL--14-40% (median 486 v. 356). The differences between results in
      serum and plasma using ELISA were similar but slightly smaller. There was no
      significant difference between CgA levels in EDTA and heparinised-plasma samples,
      and the results of measurements performed by IRMA and ELISA in most cases were
      similar. CONCLUSIONS: Referring each individual CgA result to the proposed
      reference range (or cut-off value) we must take into account whether the
      measurement is performed in plasma or in serum.

PMID- 20806178
TI  - The relationship between ghrelin levels and insulin resistance in men with
      idiopathic hypogonadotrophic hypogonadism at diagnosis and after therapy.
AB  - INTRODUCTION: It has recently been shown that ghrelin affects energy balance and
      reproductive function, but the role of ghrelin in the pathogenesis of insulin
      resistance is unclear. Firstly to assess the interaction between insulin
      resistance and ghrelin levels in hypogonadal men, and then to show the effects of
      testosterone (T) therapy on insulin and ghrelin. MATERIAL AND METHODS: Twenty
      four male patients newly diagnosed with idiopathic hypogonadotropic hypogonadism
      (IHH) and 20 healthy male subjects were enrolled in this study. Ghrelin, insulin,
      glucose, total and free testosterone levels, HOMA-IR and QUICKI, and percentage
      of body fat mass were determined at baseline in all subjects and after therapy in
      hypogonadal men. RESULTS: When compared with control subjects, hypogonadal men
      had significantly lower total and free T concentrations, ghrelin levels, and
      QUICKI whereas they had significantly higher body fat mass and HOMA-IR score.
      Following T therapy, a significant increase in ghrelin and QUICKI, and a decrease
      in HOMA-IR score and body fat mass were demonstrated in hypogonadal men.
      Calculation of the Pearson coefficient showed that ghrelin concentrations in
      hypogonadal men were positively correlated with free and total testosterone and
      QUICKI, whereas they were negatively correlated with body fat mass and HOMA-IR.
      After six months of T therapy, these correlations were still observed.
      CONCLUSIONS: Our data supports the notion that ghrelin may constitute an
      important link between the regulation of reproduction and metabolic homeostasis.

PMID- 20806179
TI  - Cardiovascular risk factors in relatives of type 2 diabetics with normal glucose
      tolerance test and elevated one-hour plasma glucose.
AB  - INTRODUCTION: To investigate the effect of elevated one hour post-load plasma
      glucose on cardiovascular risk factors, in normal glucose tolerance (NGT) people,
      who are first degree relatives of type 2 diabetics. MATERIAL AND METHODS: A cross
      sectional study on 1475 NGT subjects (Arian ethnicity), who had one hour post
      load plasma glucose was carried out. We compared the mean of age, sex, body mass
      index, waist circumference, blood pressure, lipid profile, and area under the
      curve of glucose (AUC-G) of 1190 out of 1475 NGT subjects with one hour plasma
      glucose (1hpG) >=155 mg/dL, and 285 NGT subjects with 1hpG < 155 mg/dL. RESULTS:
      The mean age, body mass index, waist circumference, blood pressure, lipid profile
      (but not low HDL-cholesterol), and area under the curve of glucose (AUC-G) was
      significantly higher in NGT subjects with 1hpG >=155 mg/dL (P < 0.05). Normal
      glucose tolerance people (first degree relatives of type 2 diabetic patients)
      with 1hpG >=155 mg/dL were older and heavier than those with 1hpG < 155 mg/dL.
      Cardiovascular risk factors (but not low HDL and hypertension) were more
      prevalent in those with elevated one hour post-load group (P < 0.05).
      CONCLUSIONS: NGT subjects with elevated one hour post-load plasma glucose (1hpG
      >=155 mg/dL) had higher prevalence of most cardiovascular risk factors in
      comparison with those with 1hpG < 155 mg/dL.

PMID- 20806180
TI  - The safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) in Iranians with
      type 2 diabetes: an open-label, non-randomised, multi-centre observational study-
      the Iran subgroup of the IMPROVETM study.
AB  - INTRODUCTION: To evaluate the clinical profile of BIAsp 30 (30% soluble insulin
      aspart, 70% protamine-crystallized insulin aspart) (NovoMix(r))30) in type 2
      diabetes patients in routine clinical practice in Iran. MATERIAL AND METHODS:
      IMPROVETM was a 26-week, multinational, open-label, non-randomized study in
      patients with type 2 diabetes. The safety and efficacy of BIAsp 30 were assessed
      at baseline and at 13 and 26 weeks. The titration of BIAsp30 was at the
      physician's discretion. RESULTS: In Iran, 478 patients (47% male) previously
      treated with oral antidiabetic drugs (OADs) (N = 159, 33.3%) and/or insulin other
      than BIAsp30 (N = 317, 66.3%) or a few who were treatment-naive (N = 2, 0.4%)
      participated in the study. After 26 weeks of treatment with BIAsp 30, the rate of
      reported major hypoglycaemic episodes was reduced by 88.1% from baseline
      (baseline v. Week 26: 0.303 v. 0.037 episodes/pt-year; p < 0.001). No significant
      differences in minor hypoglycaemic episodes between baseline and Week 26 were
      found. Glycaemic control was significantly improved from baseline to Week 26 with
      a mean HbA(1c) reduction of 1.2 +/- 1.9%. Patients' quality of life as measured
      by the DiabMedSat questionnaire significantly improved from baseline (58.1) to
      the end of the study (75.4, p < 0.001). CONCLUSIONS: BIAsp 30 therapy appeared
      safe and effective and improved quality of life in Iranian patients with type 2
      diabetes after 26 weeks of treatment.

PMID- 20806181
TI  - Urine and milk iodine concentrations in healthy and congenitally hypothyroid
      neonates and their mothers.
AB  - INTRODUCTION: In view of the high prevalence of Congenital Hypothyroidism (CH) in
      Iran, in this study we evaluated the role of iodine in the aetiology of CH by
      comparing urine and milk iodine concentrations in healthy and congenitally
      hypothyroid neonates and their mothers. MATERIAL AND METHODS: In a cross
      sectional study, urinary iodine concentrations (UIC) in newborns with CH, as well
      as UIC and the milk iodine concentrations (MIC) of their mothers, were measured
      and compared with a control group. The lower, mid, and upper range of UIC for
      neonates and lactating mothers was considered to be < 150 MUg/L, 150-230 MUg/L,
      and > 230 MUg/L, and lower, mid, and upper range of MIC was considered to be <
      150 MUg/L, 150-180 MUg/L, and > 180 MUg/L, respectively. RESULTS: The median UICs
      in subjects with CH (n = 68) and healthy subjects (n = 179) were 300.5 and 290.5
      MUg/L, respectively (P > 0.05). The median UICs in the case and control groups
      were 150 and 130 MUg/L, respectively (P > 0.05). The median MIC in the case group
      was higher than in the control group (210 MUg/L v. 170 MUg/L, P < 0.05).There was
      a positive correlation between newborn UIC and MIC. There was no significant
      correlation between newborn UIC and serum TSH, maternal UIC and maternal MIC, or
      newborn UIC and serum TSH. CONCLUSIONS: There is no inadequacy in iodine intake
      in the studied population. Iodine excess could be a possible risk factor for CH,
      but there were findings, such as lack of correlation between maternal MIC and
      UIC, and the median neonatal UIC, which was similar in the two groups, so,
      drawing conclusions should be done with some caution and requires further
      studies.

PMID- 20806182
TI  - Vitamin D status of 6- to 7-year-old children living in Isfahan, Iran.
AB  - INTRODUCTION: Vitamin D is essential for the maintenance of good health, and
      vitamin D deficiency has been reported from many countries, including those with
      a lot of sunshine. This study was conducted to evaluate the vitamin D status in
      healthy 6- to 7-year-old children in Isfahan, Iran. MATERIAL AND METHODS: Five
      hundred and thirteen healthy children were enrolled. Serum PTH and 25
      hydroxyvitamin D (25-OHD) were measured. Dietary vitamin D intake, duration of
      daily sunlight exposure, and percentage of exposed body surface area were
      determined. 25-OHD levels < 20 ng/mL and < 10 ng/mL were defined as mild and
      severe vitamin D deficiency, respectively. The ROC curve was utilized to obtain a
      local cut-off point of vitamin D deficiency. RESULTS: 25-OHD was < 20 ng/mL in 3%
      and < 33 ng/mL (local cut-off point of vitamin D deficiency) in 26% of subjects.
      Duration of sunlight exposure and daily intake of vitamin D had significant
      effects on serum level of vitamin D. CONCLUSIONS: A high prevalence of vitamin D
      deficiency in Isfahan children was observed in this study. Improvements in
      duration of sunlight exposure and daily intake of vitamin D can prevent vitamin D
      deficiency in these children.

PMID- 20806183
TI  - Chromogranin A (CgA)--the influence of various factors in vivo and in vitro, and
      existing disorders on it's concentration in blood.
AB  - Chromogranin A (CgA) is regarded as a major, nonspecific neuroendocrine tumour
      (NET) marker. The results of CgA blood concentration, however, may actually be
      influenced by various factors or coexisting pathological conditions. Among the
      factors causing a substantial increase of the blood CgA concentration are:
      treatment with proton-pump inhibitors or H2-receptor blockers, chronic atrophic
      gastritis (type A), impaired renal function, prostate cancer and BPH, and
      rheumatoid arthritis with high level of RF IgM. In addition, the sort of
      investigated biological material (whether it is serum or plasma) is of
      importance. There are also many conditions which may have a moderate or little
      influence on the concentration of CgA, among them are: inflammatory bowel disease
      (ulcerative colitis and Crohn's disease), deteriorating liver function, untreated
      essential hypertension, heart failure, hypercortisolism, pregnancy, and, in some
      subjects, ingestion of a meal. Proper assessment of the CgA results requires
      detailed knowledge about various factors, drugs, and pathological conditions
      influencing its concentration in blood.

PMID- 20806184
TI  - Insulin as the main regulator of cellular glucose utilization--aetiological
      aspects of insulin resistance.
AB  - This review presents the advances in the molecular biology and the
      pathophysiology of insulin resistance with emphasis on disturbances in cellular
      glucose transport. New scientific information about the structure and function of
      glucotransporters from the GLUT4 and SLGT families underline their significance
      in endocrinopathies and metabolic disease pathogenesis as related to insulin
      resistance. The new discoveries in this area also contribute to a better
      understanding of the regulation of insulin receptor and post-receptor reactivity
      by hormones and by drugs. They refer to the regulation of glycaemia and to its
      disturbances in diabetes mellitus, particularly of type 2, to metabolic syndrome,
      and, in general, to the pathogenesis of many syndromes and clinical disturbances
      caused by insulin resistance. Impairment of cellular glucose transport may be one
      of the primary aetiological factors in this respect. Therefore, studies of
      cellular glucotransporters expression and function promise new clinical and
      pharmacotherapeutic developments. Progress in this area has already been
      transformed into many practical proposals which are improving clinical practice.

PMID- 20806185
TI  - Postpartum hypothalamic dysfunction--a case report.
AB  - Hypothalamic dysfunction is a rarely diagnosed endocrine disorder resulting from
      various pathological processes affecting this brain region. It is characterized
      by a complex clinical manifestation, including headaches, abnormal regulation of
      various behaviours, abnormalities in sleeping and thermoregulation, and
      inappropriate secretion of many hormones. In our paper, we report the case of a
      29-year-old female in whom hypothalamic dysfunction was induced by delivery
      complications. Accurate diagnosis of this syndrome required complex laboratory
      and imaging tests. The disease-related obesity was resistant to conventional
      treatment (diet and pharmacotherapy) and only bariatric surgery caused a
      reduction of body mass. The described patient is the first with postpartum
      hypothalamic dysfunction in whom plasma levels of adipokines, neuropeptides, and
      alimentary tract hormones contributing to physiological regulation of food intake
      were assessed.

PMID- 20806186
TI  - Diagnostic dilemmas in a patient with anaemia. Empty sella syndrome--a case
      report.
AB  - Empty sella syndrome is defined as a group of clinical symptoms developing as a
      result of herniation of the subarachnoid space within the sella, which is often
      associated with some degree of flattening of the pituitary gland. It is usually
      recognized incidentally during brain imaging studies performed for different
      indications, and in most cases this condition is asymptomatic. However, it may
      result in impairment of various endocrine glands, for which the pituitary gland
      produces its crinins. Despite the high incidence of empty sella syndrome (up to
      about 5% of the population) it is commonly ignored as the cause of various
      symptoms. We present a case of 55-year-old patient admitted to the department of
      internal medicine due to anaemia and progressive weakness, with recognized
      hypothyroidism and adrenal gland insufficiency in the course of empty sella
      syndrome.

PMID- 20806187
TI  - Methods of hair loss evaluation in patients with endocrine disorders.
AB  - Hair loss may accompany several endocrine disorders, including hypopituitarism,
      hypothyreosis, hyperthyreosis, hypoparathyroidism, diabetes mellitus, growth
      hormone deficiency, hyperprolactinaemia, polycystic ovary syndrome, SAHA
      syndrome, congenital adrenal hyperplasia, Cushing syndrome, or virilising
      tumours. Most patients with endocrine disorders present with diffuse non-scarring
      alopecia, such as anagen effluvium, telogen effluvium or androgenetic alopecia.
      Focal non-scarring alopecia, such as alopecia areata coexisting with autoimmune
      thyroiditis, is less frequent and scarring alopecia is a rare finding in patients
      with endocrine abnormalities. In some cases an endocrine disorder may be
      suspected based on dermatological findings during hair loss evaluation. Classic
      methods of hair evaluation include hair weighing, pull test, wash test, the
      trichogram, and histopathological examination. Newly developed non-invasive
      diagnostic techniques include the phototrichogram, trichoscan, trichoscopy, and
      reflectance confocal microscopy.

PMID- 20806188
TI  - Transsexualism--diagnostic and therapeutic aspects.
AB  - Gender identity disorder (GID, transsexualism) is a multidisciplinary problem of
      an unclear aetiology. Although the diagnosis of GID is generally established by
      psychiatrists, the diagnostic team always includes an endocrinologist, who is
      responsible for hormonal therapy. Hormonal therapy is the first step in the sex
      reassignment procedure and requires careful monitoring in the initial phase and
      in later years of treatment. In this paper we review the latest aspects of the
      diagnosis and treatment of transsexualism and the most common complications of
      hormonal intervention.

PMID- 20806190
TI  - Clinical characteristics of Polish women with ST-segment elevation myocardial
      infarction.
AB  - BACKGROUND: Differences in clinical manifestation, therapeutic strategies and
      prognosis in men and women with acute coronary syndromes became crucial in the
      last decade. AIM: To present clinical characteristics of Polish women with ST
      segment elevation myocardial infarction (STEMI). METHODS: A total of 26,035
      patients with STEMI (8989 females, 34.5%) were included between 01.06.2005 and
      31.05.2006. Data were obtained from the Polish Registry of Acute Coronary
      Syndromes (PL-ACS). RESULTS: Women were older than men. The incidence of
      classical risk factors, anterior infarction, atrial fibrillation, higher heart
      rate, cardiac arrest, pulmonary oedema and cardiogenic shock was higher in women.
      Coronary angiography was performed in 58.7% of patients, significantly less in
      women. There was a longer time delay in women at each stage of treatment. In
      hospital and 12-month mortality was significantly higher in women. Pulmonary
      oedema, cardiogenic shock, cardiac arrest, age, diabetes and anterior infarction
      were independent factors of risk of death in multifactorial analyses, both in in
      hospital and long term observation. CONCLUSIONS: Basic clinical characteristics
      of women with STEMI is poorer than in men. Women have longer time delay at each
      stage of treatment. Invasive strategy was less frequently applied in women.
      Independent predictors of death are similar in men and in women. Both in-hospital
      and one year mortality is higher in women.

PMID- 20806191
TI  - [Comment to article Clinical characteristics of Polish women with ST-segment
      elevation myocardial infarction].

PMID- 20806192
TI  - Acute coronary syndrome - a frequent clinical manifestation of bare metal in
      stent restenosis.
AB  - BACKGROUND: In-stent restenosis (ISR) complicates 20-30% of percutaneous coronary
      interventions (PCI) with bare metal stent (BMS) implantation. Although the
      widespread use of drug eluting stents (DES) across Europe caused a considerable
      reduction of BMS implantations, their number is still lower than the number of
      BMS implantations in several countries. AIM: The clinical presentation of ISR has
      not been well characterissed. Thus, we attempted to analyze this condition and
      assess the treatment of ISR in everyday clinical practice. METHODS: We searched
      our database for all cases of bare metal ISR between 1999 and 2007. Follow-up
      angiography after PCI was not a routine procedure but a clinically driven
      examination. Clinical presentations of ISR were divided into: stable angina, and
      acute coronary syndromes (ACS), i.e. unstable angina (UA) and myocardial
      infarction (MI) (further subdivided into NSTEMI and STEMI). Analysis included
      variables associated with different clinical manifestations, methods of ISR
      treatment and in-hospital complications of ISR. RESULTS: In-stent restenosis was
      identified in 432 (3%) of 15,910 patients who underwent PCI. The mean age was
      61.6 + or - 15.6 (27-86) years, and 295 (68.3%) patients were men. Risk factor
      distribution was typical for a Caucasian population. Recurrent clinical episode
      occurred at a mean of 7 (1-108) months after PCI. Exertional angina was present
      in 245 (56.7%) patients, UA in 128 (29.6%) patients and MI in 59 (13.7%)
      patients, including STEMI in 28 (6.5%) and NSTEMI in 31 (7.2%) patients. Overall,
      ACS was diagnosed in 187 patients or 43.3% of all cases of ISR. Multivariate
      analysis showed a positive correlation between previous MI and younger age and
      ACS as the clinical manifestation of ISR, and a negative correlation between more
      severe restenosis and ACS manifestation. The incidence of clinical complications
      (MI or death) was higher in patients with ACS as the clinical manifestation of
      ISR (6.9% vs 1.6%). CONCLUSIONS: In-stent restenosis after BMS implantation is a
      serious clinical problem. More than 40% of patients with ISR present with ACS,
      including 13.7% patients with MI, more frequently among younger patients and
      patients with previous MI. Most patients with ISR are treated with repeated PCI
      with high success rate (97.7%), although the risk of clinical complications is
      considerably higher in patients presenting with ACS.

PMID- 20806193
TI  - [Comment to article Acute coronary syndrome - a frequent clinical manifestation
      of bare metal in-stent restenosis].

PMID- 20806194
TI  - Leptin in acute myocardial infarction and period of convalescence in patients
      with type 2 diabetes mellitus.
AB  - BACKGROUND: Leptin is a protein produced in adipose tissue and takes part in
      angiogenesis and atherogenesis. Leptin is associated with development of type 2
      diabetes and cardiovascular disease. AIM: To evaluate leptin concentrations in
      acute myocardial infarction and in the period of convalescence in patients with
      type 2 diabetes mellitus. METHODS: Coronary angiography was performed in 58
      patients with acute myocardial infarction. The study group comprised 35 patients
      with type 2 diabetes mellitus (DM) (25 men, 10 women, mean age 63.8 + or - 11.5
      years) and 23 non-diabetic subjects (17 men, 6 women, mean age 58.6 + or - 9.9
      years) - the control group. All patients underwent medical examination and body
      mass indices (BMI) as well as waist/hip ratios (WHR) were calculated. Venous
      blood was collected after 24 hours of admission (second day), on day 5 and three
      weeks after admission. RESULTS: Leptin level was significantly associated with
      BMI (DM: r = 0.46, p = 0.005; control group: r = 0.67, p < 0.01), and hip
      circumference (DM: r = 0.28, p = 0.09; control group: r = 0.41, p = 0.04). Plasma
      leptin levels in women with type 2 diabetes were higher than in men (32.1 + or -
      11.7 microg/mL vs 12.7 + or - 11.2 microg/mL, p < 0.01). Plasma leptin levels
      were significantly lower in non-diabetics compared to diabetic patients. Plasma
      leptin levels in diabetic patients were significantly higher in the acute phase
      of myocardial infarction than in the period of convalescence (18.3 + or - 14.3
      microg/mL, 16.1 + or - 12.8 microg/mL, 14.8 + or - + or - 11.2 microg/mL, p =
      0.02) but not in the control group (10.6 + or - 8.2 microg/mL, 10.0 + or - 7.3
      microg/mL, 9.6 + or - 7.0 microg/mL, NS). CONCLUSIONS: Plasma leptin levels in
      diabetic patients were significantly higher in the acute myocardial infarction
      than in the period of convalescence. These findings suggests that leptin may play
      an important role in the metabolic changes taking place during the first days of
      myocardial infarction.

PMID- 20806195
TI  - [Comment to article Leptin in acute myocardial infarction and period of
      convalescence in patients with type 2 diabetes mellitus].

PMID- 20806196
TI  - Prevalence and predictors of pulmonary hypertension in elderly patients with
      isolated diastolic heart failure.
AB  - BACKGROUND: Despite the growing recognition that pulmonary hypertension can
      develop in diastolic heart failure; its clinical significance remains poorly
      defined. AIM: We sought to explore the prevalence and predictors of pulmonary
      hypertension in elderly patients with isolated diastolic heart failure. METHODS:
      We enrolled 100 consecutive elderly patients with isolated diastolic heart
      failure. All patients underwent transthoracic echocardiography to measure the
      pulmonary artery systolic pressure, diastolic function indices (mitral E peak
      deceleration time, isovolumetric relaxation time, early mitral annular diastolic
      velocity), left atrial diameter and left ventricular mass index. Pulmonary
      hypertension was defined as pulmonary artery systolic pressure > or = 37 mm Hg.
      We classified patients into two groups: one with diastolic heart failure and
      concomitant pulmonary hypertension, and one with diastolic heart failure but
      without concomitant pulmonary hypertension. RESULTS: The mean age of the whole
      series was 65.4 + or - 5.4 years, 49 (49%) being female. Patients with pulmonary
      hypertension (20% of the whole series) were more often females, hypertensive,
      more likely to have atrial fibrillation, pulmonary congestion symptoms, larger
      left atrial diameter, lower early mitral annular diastolic velocity, lower left
      ventricular ejection fraction, and more likely to have mitral regurgitation (p <
      0.05 for all). Multivariate logistic regression analysis identified female
      gender, atrial fibrillation, and early mitral annular diastolic velocity (e') as
      the independent predictors of the presence of pulmonary hypertension.
      CONCLUSIONS: Pulmonary hypertension is fairly prevalent in elderly patients with
      diastolic heart failure. Female gender, atrial fibrillation, and early mitral
      annular diastolic velocity (e') were the independent predictors of the presence
      of pulmonary hypertension in this patient group.

PMID- 20806197
TI  - [Comment to article Prevalence and predictors of pulmonary hypertension in
      elderly patients with isolated diastolic heart failure].

PMID- 20806198
TI  - Paediatric heart transplantation - the impact of a ventricular assist device on
      operative outcomes.
AB  - BACKGROUND: The use of a ventricular assist device (VAD) is a life-saving option
      for patients with heart failure refractory to conventional therapy. AIM: To
      assess the effect of VAD on outcomes of heart transplantation in children.
      METHODS: Between October 1988 and June 2009, a consecutive series of 95 children
      (mean age 8.6 + or - 6.7 years, range 5 days-17.9 years) underwent heart
      transplantation: patients in group 1 (n = 11) received VAD as a bridge to cardiac
      transplantation (left ventricular VAD in 4, biventricular VAD in 7), and patients
      in group 2 (n = 84) underwent heart transplantation without previous cardiac
      support using VAD. The indication for heart transplantation was
      cardiomyopathy/myocarditis in 66 (69.5%) of children and congenital heart disease
      in 29 (30.5%) patients. RESULTS: Congenital heart disease was diagnosed more
      often in group 2 than in group 1 (p = 0.047). The two groups did not differ
      significantly with respect to age, weight and parameters of preoperative liver
      and kidney function (except for aspartate aminotransferase activity, p = 0.020).
      The mean waiting time for transplantation was 64.2 + or - 87.4 days (range 1-443
      days) and did not differ between the groups. The mean follow-up was 6.8 + or -
      5.4 years (range 1 day-17.6 years). Mortality during long-term follow-up was 9.1%
      (n = 1) in group 1 and 20.2% (n=17) in group 2 (p = 0.632). We found no
      significant differences in postoperative ventilatory support time (p = 0.773),
      duration of hospital stay (p = 0.853), and incidence of acute rejection episodes
      (p = 0.575). CONCLUSIONS: The use of VAD as a bridge to heart transplantation in
      children with severe heart failure had no negative effect on treatment outcomes.

PMID- 20806199
TI  - [Comment to article Paediatric heart transplantation - the impact of a
      ventricular assist device on operative outcomes].

PMID- 20806200
TI  - Ten-year risk of fatal cardiovascular disease in the Polish population and
      medical care. Results of the WOBASZ study.
AB  - BACKGROUND: An individual assessment of global risk of death from cardiovascular
      diseases (CVD) should guide management, both life style changes and medical
      therapy, in order to decrease risk factors and improve prognosis. AIM: We
      assessed global risk in the Polish population and its relation to medical care,
      including blood pressure and cholesterol measurements, smoking cessation and
      dietary advice, and recommendations regarding increased physical activity.
      METHODS: A sample of the Polish population including 6392 men and 7153 women aged
      20-74 years was screened in 2003-2005. We calculated global risk for subjects
      aged 40-70 years using the SCORE function for high-risk regions of Europe.
      RESULTS: We found high global risk (> or = 5%) in 46% of men and 21% of women.
      Compared to low risk subjects, high risk subjects more often had
      hypercholesterolaemia, hypertension or were obese, and they more often visited
      their primary care physicians. Dietary advice was given to 36% of high global
      risk men compared to only 20% of low global risk men with hypercholesterolaemia
      (47% vs 23% among women, respectively p < 0.0001), and cholesterol measurement
      was made in 31% of high global risk men and 19% of low global risk men with
      hypercholesterolaemia (38% vs 27% among women, respectively p < 0.0001). Smokers
      with high global risk received smoking cessation advice significantly more often
      than low global risk smokers (men: 72% vs 55%; women: 63% vs 52%). Subjects with
      hypertension and high global risk had their blood pressure measured significantly
      more often than those with hypertension and low global risk (men: 83% vs 68%;
      women: 87% vs 79%). High-risk obese persons significantly more often received
      both dietary advice (men: 55% vs 36%; women: 60% vs 34%) and recommendations
      regarding higher physical activity (men: 43% vs 32%; women: 40% vs 27%). In the
      logistic regression analysis, the quality of medical care was significantly
      associated with the global risk. CONCLUSIONS: The Polish population is
      characterised by a high proportion of subjects with high global risk especially
      among men. The quality of medical care was found to be associated with the global
      risk level: the higher was the global risk, the better was the medical care,
      although it is still insufficient compared to current standards.

PMID- 20806201
TI  - [Uncommon presentation of venous thromboembolism and fatal systemic emboli in a
      patient with nonbacterial thrombotic endocarditis due to pancreatic cancer].
AB  - In the presented case of a 60-year-old man, deep vein thrombosis and pulmonary
      embolism symptoms preceded pancreatic cancer diagnosis. An unexpected
      echocardiographic finding was a longitudinal mass attached to the tricuspid
      valve, and extending to the pulmonary artery - suggestive of a thrombus (as
      confirmed further autopsy), probably embolic in origin. This uncommon situation
      might be due to nonbacterial thrombotic endocarditis, which involved all, but
      mainly tricuspid and aortic valves. During heparin therapy the patient's
      haemodynamic status was stable until systemic emboli occurred with multifocal
      ischaemic stroke that was the cause of death.

PMID- 20806202
TI  - Ivabradine as a heart rate-lowering agent in a patient with end-stage renal
      failure after heart transplantation.
AB  - A 56 year-old woman with a transplanted heart, with arterial hypertension and
      chronic pulmonary obstructive disease, was hospitalised because of palpitations,
      dyspnea, chest pain and oedema. After cyclosporine treatment she was diagnosed
      with renal failure, which was treated by hemodialysis. Heart rate (HR) at
      admission was 100, mean HR in 24-hour Holter monitoring was 106 bpm. Ivabradine
      was added to the treatment. The dose of 2.5 mg bid was doubled after three days.
      Mean HR in control Holter monitoring was 81. Ivabradine was well tolerated in
      this patient. The clinical benefits were observed soon after application and
      maintained during the follow-up.

PMID- 20806203
TI  - [A 31 year-old female with recurrent pericardial effusion. Diagnostic and
      therapeutic difficulties].
AB  - We present a case of a 31 year-old female with recurrent pericarditis. Despite
      pharmacological treatment with nonsteroidal anti-inflammatory drugs, steroids,
      diuretics and antibiotics the symptoms of cardiac tamponade occurred. The patient
      required pericardiocentesis with pericardial drainage. In about 30% of cases the
      specific etiology it ts not detecting using the routine tests.

PMID- 20806205
TI  - [Big myxoma of the left atrium suggesting pulmonary embolism].
AB  - Cardiac myxomas are rare. They usually appear as a sporadic isolated mass in the
      left atrium of women with no other pathology. Our patient had symptoms which may
      suggest pulmonary embolism (PE)-TTE, D-dimers, ECG, laboratory findings seemed to
      confirm acute PE. Physical examination was unremarkable. Signs of pulmonary
      hypertension and shortened acceleration time also suggested PE. However, angio-CT
      excluded it. The patient was transfered to surgical department. During the
      operation the big myxoma filling the whole space of the left atrium and blocking
      the entrance to the left ventricle was found and easily removed. Kardiol Pol
      2010; 68, 6: 695-696.

PMID- 20806207
TI  - [Patient after acute coronary syndrome on antiplatelet therapy. Inhibition of
      coagulation processes may decrease the occurence of major cardiovascular events].

PMID- 20806208
TI  - [Strategies of preoperative evaluation and risk reduction in patients undergoing
      invasive procedures in the view of recent European Society of Cardiology
      guidelines].
AB  - In this article we summarise recent European Society of Cardiology guidelines on
      perioperative evaluation and management of patients undergoing invasive non
      cardiac procedures. Close attention is paid to pharmacological methods of risk
      reduction including beta-blockers, statins, aspirin and angiotensin converting
      enzyme inhibitors. Simple, stepwise and evidence-based algorithm for patient
      evaluation is presented. We discuss the need for excessive diagnostic tests and
      coronary revascularisation before the procedure. Time frame for stopping dual
      antiplatelet therapy following percutaneous coronary interventions, methods of
      glycaemic control and bridging protocol for patients on oral anticoagulants are
      also provided. We emphasise the importance of prompt implementation of the above
      guidelines as the number of surgical procedures being performed in high risk
      patients (including the elderly) constantly rises.

PMID- 20806209
TI  - Brugada sign unmasking the location of an acute myocardial infarction.
AB  - Two patients with acute myocardial infarction were admitted with unremarkable
      electrocardiograms, which did not reveal the location of the damage. A review of
      these electrocardiograms led to a suspicion of the presence of Brugada sign
      (BRSG), something subsequently confirmed by the administration of a sodium
      channel blocker. The unmasking of BRSG was unexpectedly accompanied by
      repolarisation abnormalities, showing ischaemia in the lateral wall, concordant
      with the distribution of the culprit vessels in the coronary angiogram.

PMID- 20806211
TI  - [Two rare cases of left ventricular non-compaction diagnosed in elderly
      patients].
AB  - Isolated non-compaction of the left ventricle (LVNC) is a rare disorder,
      classified as a primary genetic or unclassified cardiomyopathy. Left ventricular
      non-compaction is characterised by an altered myocardial wall with prominent
      trabeculae and deep intertrabecular recesses caused by intrauterine arrest of
      compaction. This anomaly creates two layers consisting of compacted and non
      compacted myocardium. Left ventricular non-compaction is associated with high
      rates of morbidity and mortality in adults with no specific therapy. We report
      two rare cases of LVNC diagnosed in elderly patients.

PMID- 20806212
TI  - Management of coronary air embolism during coronary stenting.
AB  - Coronary air embolism is a rare complication of cardiac catheterisation. We
      describe an alternative method of managing this complication which may be
      preferable to conventional methods.

PMID- 20806214
TI  - [Radiofrequency ablation and cardioneuroablation for AVNRT and atrioventricular
      block].
AB  - We describe a case of a 35 year-old woman with AVNRT and AVB successfully treated
      with radiofrequency ablation. Prior to the procedure, PR interval was very
      prolonged (420 ms) and second degree Wenckebach AV block during sinus rythm with
      heart rate below 80/min was seen. After the successful RF ablation an improvement
      in atrio-ventricular conduction with disappearance of Wenckebach periodicity was
      achieved. This case shows that there is a possibility of successful elimination
      of slow pathway with improvement in AV conduction.

PMID- 20806215
TI  - [Commentary to the article: Van Gelder IC, Groenveld HF, Crijns HJ et al. Lenient
      versus strict rate control in patients with atrial fibrillation].

PMID- 20806217
TI  - [Methodology and safety of transvascular reduction of severe ischaemic mitral
      insufficiency with MitraClip in high-surgical-risk patients - first three cases
      in Poland].
AB  - The authors present the results of minimally invasive transvascular reduction of
      severe mitral insufficiency in the first three patients with extensive
      postinfarction cardiac injury treated in Poland. The positive early in-hospital
      outcomes in the first three patients encourage further implementation of this
      treatment method in patients with postinfarction cardiomyopathy and high
      perioperative risk.

PMID- 20806218
TI  - [PM/ICD lead extraction - most difficult and potentially hazardous electrotherapy
      procedure - logistic and training problems].

PMID- 20806220
TI  - Order within disorder: aggrecan chondroitin sulphate-attachment region provides
      new structural insights into protein sequences classified as disordered.
AB  - Structural investigation of proteins containing large stretches of sequences
      without predicted secondary structure is the focus of much increased attention.
      Here, we have produced an unglycosylated 30 kDa peptide from the chondroitin
      sulphate (CS)-attachment region of human aggrecan (CS-peptide), which was
      predicted to be intrinsically disordered and compared its structure with the
      adjacent aggrecan G3 domain. Biophysical analyses, including analytical
      ultracentrifugation, light scattering, and circular dichroism showed that the CS
      peptide had an elongated and stiffened conformation in contrast to the globular
      G3 domain. The results suggested that it contained significant secondary
      structure, which was sensitive to urea, and we propose that the CS-peptide forms
      an elongated wormlike molecule based on a dynamic range of energetically
      equivalent secondary structures stabilized by hydrogen bonds. The dimensions of
      the structure predicted from small-angle X-ray scattering analysis were
      compatible with EM images of fully glycosylated aggrecan and a partly
      glycosylated aggrecan CS2-G3 construct. The semiordered structure identified in
      CS-peptide was not predicted by common structural algorithms and identified a
      potentially distinct class of semiordered structure within sequences currently
      identified as disordered. Sequence comparisons suggested some evidence for
      comparable structures in proteins encoded by other genes (PRG4, MUC5B, and CBP).
      The function of these semiordered sequences may serve to spatially position
      attached folded modules and/or to present polypeptides for modification, such as
      glycosylation, and to provide templates for the multiple pleiotropic interactions
      proposed for disordered proteins.

PMID- 20806221
TI  - Potential anti-bacterial drug target: structural characterization of 3,4
      dihydroxy-2-butanone-4-phosphate synthase from Salmonella typhimurium LT2.
AB  - 3,4-Dihydroxy-2-butanone-4-phosphate synthase (DHBPS) encoded by ribB gene is one
      of the first enzymes in riboflavin biosynthesis pathway and catalyzes the
      conversion of ribulose-5-phosphate (Ru5P) to 3,4-dihydroxy-2-butanone-4-phosphate
      and formate. DHBPS is an attractive target for developing anti-bacterial drugs as
      this enzyme is essential for pathogens, but absent in humans. The recombinant
      DHBPS enzyme of Salmonella requires magnesium ion for its activity and catalyzes
      the formation of 3,4-dihydroxy-2-butanone-4-phosphate from Ru5P at a rate of 199
      nmol min(-1) mg(-1) with K(m) value of 116 MUM at 37 degrees C. Further, we have
      determined the crystal structures of Salmonella DHBPS in complex with sulfate,
      Ru5P and sulfate-zinc ion at a resolution of 2.80, 2.52, and 1.86 A,
      respectively. Analysis of these crystal structures reveals that the acidic loop
      (residues 34-39) responsible for the acid-base catalysis is disordered in the
      absence of substrate or metal ion at the active site. Upon binding either
      substrate or sulfate and metal ions, the acidic loop becomes stabilized, adopts a
      closed conformation and interacts with the substrate. Our structure for the first
      time reveals that binding of substrate Ru5P alone is sufficient for the
      stabilization of the acidic active site loop into a closed conformation. In
      addition, the Glu38 residue from the acidic active site loop undergoes a
      conformational change upon Ru5P binding, which helps in positioning the second
      metal ion that stabilizes the Ru5P and the reaction intermediates. This is the
      first structural report of DHBPS in complex with either substrate or metal ion
      from any eubacteria.

PMID- 20806222
TI  - Structural facets of disease-linked human prion protein mutants: a molecular
      dynamic study.
AB  - Prion propagation in transmissible spongiform encephalopathies involves the
      conversion of the cellular prion protein, PrPC, into the pathogenic conformer
      PrPSc. Human familial forms of the disease are linked to specific mutations in
      the PrP gene, PRNP, and include Gerstmann-Strussler-Scheinker syndrome (GSS),
      familial Creutzfeldt-Jakob disease (fCJD), and fatal familial insomnia. To gain
      insights into the molecular basis of these disorders, we performed 200 ns of
      classical molecular dynamic simulations in aqueous solution on wild type (WT)
      human PrP (HuPrP), and on three HuPrP variants located in the globular HuPrP
      domain: two pathological mutations, HuPrP(Q212P) and HuPrP(E200K), linked to GSS
      and to fCJD respectively, and one protective polymorphism, HuPrP(E219K) (total
      time-scale simulated 800 ns). A comparison between the predicted structural
      determinants of WT HuPrP and HuPrP(E200K) with their NMR structures established
      the accuracy of the methods used. Strikingly, the analyzed disease-linked
      variants produced their major effect on the alpha2-alpha3 region and the beta2
      alpha2 loop, regardless of the mutation position. The conformational change of
      the latter might affect the interactions with cellular partners in the
      fibrillation process. The protocol proposed here represents a powerful approach
      for reproducing the structural effects of genetic mutations located in the
      globular domain of HuPrP, such as the GSS-related HuPrP(Q212P) and the protective
      polymorphism HuPrP(E219K).

PMID- 20806223
TI  - The 2009 Human Liver Proteome Project (HLPP) Workshop 26 September 2009, Toronto,
      Canada.
AB  - The Human Liver Proteome Project (HLPP) was formally launched by HUPO in 2002.
      The 11th HLPP Workshop was held on September 26th, 2009 during the 8th HUPO World
      Congress in Toronto, Canada. The representative progresses were presented from
      four groups. Subsequently, the workshop ended with a lively discussion on four
      topics related to the project as well as other initiatives.

PMID- 20806224
TI  - Tackling quantitation: a report on the annual Spring Workshop of the HUPO-PSI 28
      30 March 2010, Seoul, South Korea.
AB  - The annual Spring Workshop of the HUPO-PSI took place in Korea, where the Mass
      Spectrometry and Protein Separations groups joined forces to tackle the issue of
      the consistent reporting of quantitative proteomic data generated by mass
      spectrometry-based technologies. A preliminary mzQuantML schema was drafted
      which, when completed and tested, will complement the existing mzIdentML schema
      for reporting protein identifications. The Molecular Interactions group
      concentrated on the implementations of the PSICQUIC (PSI Common Query InterfaCe)
      service that allows users to simultaneously query interaction data across
      multiple participating resources. Work was also undertaken to update the MIAPE
      guidelines, in response to feedback from the editors of a number of proteomic
      journals.

PMID- 20806225
TI  - A quantitative proteomic analysis of biofilm adaptation by the periodontal
      pathogen Tannerella forsythia.
AB  - Tannerella forsythia is a Gram-negative anaerobe that is one of the most
      prominent inhabitants of the sub-gingival plaque biofilm, which is crucial for
      causing periodontitis. We have used iTRAQ proteomics to identify and quantify
      alterations in global protein expression of T. forsythia during growth in a
      biofilm. This is the first proteomic study concentrating on biofilm growth in
      this key periodontal pathogen, and this study has identified several changes in
      protein expression. Moreover, we introduce a rigorous statistical method
      utilising peptide-level intensities of iTRAQ reporters to determine which
      proteins are significantly regulated. In total, 348 proteins were identified and
      quantified with the expression of 44 proteins being significantly altered between
      biofilm and planktonic cells. We identified proteins from all cell compartments,
      and highlighted a marked upregulation in the relative abundances of predicted
      outer membrane proteins in biofilm cells. These included putative transport
      systems and the T. forsythia S-layer proteins. These data and our finding that
      the butyrate production pathway is markedly downregulated in biofilms indicate
      possible alterations in host interaction capability. We also identified
      upregulation of putative oxidative stress response proteins, and showed that
      biofilm cells are 10 to 20 fold more resistant to oxidative stress. This may
      represent an important adaptation of this organism to prolonged persistence and
      immune evasion in the oral cavity.

PMID- 20806226
TI  - Towards a two-dimensional proteomic reference map of Bradyrhizobium japonicum
      CPAC 15: spotlighting "hypothetical proteins".
AB  - The economic and ecological importance of the symbiosis of soybean with
      Bradyrhizobium japonicum strains is significant in several countries,
      particularly Brazil; however, up to now, only one complete and a draft genome for
      this species are available. In this study, we have obtained a proteomic reference
      map of B. japonicum strain CPAC 15 (=SEMIA 5079) - used in commercial inoculants
      for application to soybean crops in Brazil - grown under in vitro conditions.
      CPAC 15 belongs to the same serogroup as strain USDA 123, and both are known as
      the soybean bradyrhizobial strains with highest competitive and saprophytic known
      so far. To increase the precision of the proteomic map, we compared whole-cell 2
      D protein gel-electrophoresis profiles of CPAC 15 and of two related strains. One
      hundred and seventy representative spots, selected from the three profiles, were
      analyzed by MS. In total, 148 spots were successfully identified as cytoplasmic
      and periplasmic proteins belonging to diverse metabolic pathways, several of them
      related to the saprophytic and competitive abilities of CPAC 15. We attributed
      probable functions to 26 hypothetical proteins, including those involved in
      polyhydroxybutyrate metabolism, beta-lactamase, stress responses and aromatic
      compound degradation, all with high probability of being related to the
      saprophytic ability of CPAC 15. In addition, by providing valuable information
      about expressed proteins in B. japonicum in vitro, our results emphasize the
      importance of accurate functional annotation of uncharacterized expressed
      proteins, improving considerably our understanding of the legume-rhizobia
      symbiosis.

PMID- 20806227
TI  - Implementation of spin-echo blood oxygen level-dependent (BOLD) functional MRI in
      birds.
AB  - The advent of high-field MRI systems has allowed the implementation of blood
      oxygen level-dependent functional MRI (BOLD fMRI) on small animals. An increased
      magnetic field improves the signal-to-noise ratio and thus allows an improvement
      in the spatial resolution. However, it also increases susceptibility artefacts in
      the commonly acquired gradient-echo images. This problem is particularly
      prominent in songbird MRI because of the presence of numerous air cavities in the
      skull of birds. These T(2)*-related image artefacts can be circumvented using
      spin-echo BOLD fMRI. In this article, we describe the implementation of spin-echo
      BOLD fMRI in zebra finches, a small songbird of 15-25 g, extensively studied in
      the behavioural neurosciences of birdsong. Because the main topics in this
      research domain are song perception and song learning, the protocol implemented
      used auditory stimuli. Despite the auditory nature of the stimuli and the weak
      contrast-to-noise ratio of spin-echo BOLD fMRI compared with gradient-echo BOLD
      fMRI, we succeeded in detecting statistically significant differences in BOLD
      responses triggered by different stimuli. This study shows that spin-echo BOLD
      fMRI is a viable approach for the investigation of auditory processing in the
      whole brain of small songbirds. It can also be applied to study auditory
      processing in other small animals, as well as other sensory modalities.

PMID- 20806228
TI  - Region-specific changes in ascorbate concentration during rat brain development
      quantified by in vivo (1)H NMR spectroscopy.
AB  - Ascorbate (vitamin C, Asc) was quantified in vivo using short-TE (1)H NMR spectra
      from a previously published study on regional and developmental changes in the
      neurochemical profile of the rat brain (Tkac I, Rao R, Georgieff MK, Gruetter R.
      Magn Reson Med. 2003; 50: 24-32). Asc concentration was quantified on postnatal
      days P7-P28 from three regions that are of interest in the study of
      neurocognitive development, i.e. the hippocampus, striatum and cerebral cortex.
      The previously measured (1)H NMR spectra were re-analyzed using LCModel with the
      Asc spectrum included in the basis set. The Asc concentration was consistently
      quantified from all 110 re-analyzed spectra with an estimated fitting error of 7%
      (i.e. the average Cramer-Rao lower bound). The sensitivity of Asc quantification
      was sufficiently high to detect regional and developmental changes in Asc
      concentration. The concentration of Asc was highest on P7, and decreased with age
      in all three brain regions (p < 0.001) in agreement with previous in vitro
      studies. At P10 and older postnatal ages, an inhomogeneous distribution of Asc
      among brain regions was detected. In addition to facilitating the quantification
      of this important antioxidant concentration, the inclusion of the Asc spectrum in
      the LCModel basis set improved the quantification accuracy of other brain
      metabolite concentrations in the neurochemical profile.

PMID- 20806229
TI  - Distribution of lymphoid neoplasms in the Republic of Korea: analysis of 5318
      cases according to the World Health Organization classification.
AB  - Compared with the West, the overall incidence of lymphoid neoplasms is lower, and
      the subtype distribution is distinct in Asia. To comprehensively investigate the
      subtype distribution with the age and sex factors, and temporal changes of
      subtype proportions, we re-assessed all patients with lymphoid neoplasms
      diagnosed at a large oncology service in the Republic of Korea from 1989 to 2008
      using the World Health Organization classifications. Of the total 5,318 patients,
      66.9% had mature B-cell neoplasms, 12.5% had mature T/natural killer (NK)-cell
      neoplasms, 16.4% had precursor lymphoblastic leukemia/lymphoma (ALL/LBL), and
      4.1% had Hodgkin's lymphoma. The most common subtypes were diffuse large B-cell
      lymphoma (30.5%), plasma cell myeloma (14.0%), extranodal marginal zone lymphoma
      of mucosa-associated lymphoid tissue type (MALT lymphoma; 12.4%), B-cell ALL/LBL
      (11.3%), Hodgkin's lymphoma (4.1%), peripheral T-cell lymphoma unspecified
      (4.0%), T-cell ALL/LBL (3.9%), and extranodal NK/T-cell lymphoma of nasal type
      (3.9%). Most subtypes showed male predominance, with an average M/F ratio of 1.3.
      Most mature lymphoid neoplasms were diseases of adults (mean age, 53.5 yr),
      whereas ALL/LBLs were of young individuals (mean age, 20.3 yr). When the relative
      proportion of subtypes were compared between two decades (1989-1998 vs. 1999
      2008), especially MALT lymphoma has increased in proportion, whereas T/NK-cell
      neoplasms and ALL/LBL have slightly decreased. In summary, the lymphoid neoplasms
      of Koreans shared some epidemiologic features similar to those of other
      countries, whereas some subtypes showed distinct features. Although the increase
      in incidence of lymphoid neoplasms is relatively modest in Korea, recent increase
      of MALT lymphoma and decrease of T/NK-cell neoplasms and ALL/LBL are interesting
      findings.

PMID- 20806231
TI  - Development and validation of a pediatric severity index for sickle cell
      patients.
AB  - There is no instrument to measure severity of sickle cell disease (SCD) in
      pediatric patients that is generally accepted. The aim of this study was to
      develop and validate a severity index for SCD in children. We developed an index
      consisting of 12 items and tested its validity of the index using data from 92
      children. We tested whether different scores were obtained for patients
      classified by severity both subjectively and objectively by a partially validated
      existing index. Furthermore, we tested whether the index could differentiate
      patients classified according to genotype or the number of alpha-gene deletions
      and evaluated whether the score on the index was correlated with the average
      number and days of hospitalizations/year, age and a risk of death score. We
      explored the effect of three different weighting systems (Score A, B, and C) to
      summarize these items. All weightings demonstrated a significant difference
      between the scores of mild, moderate, and severely affected patients, as
      classified by a subjective rating or with an existing index (P < 0.01). The index
      clearly differentiated patients by genotype (P < 0.01) or alpha-gene deletions (P
      < 0.01). The correlation with hospitalization was moderate. Age and the risk of
      death score were weakly associated with the pediatric severity index for SCD.
      This is the first pediatric SCD severity index that was developed and validated
      using modern clinimetric methodology. The validity and reliability of this index
      should be further evaluated in a prospective study including a larger cohort,
      preferably diagnosed at birth.

PMID- 20806230
TI  - Symptoms of depression and anxiety in patients with thalassemia: prevalence and
      correlates in the thalassemia longitudinal cohort.
AB  - Thalassemia is an inherited blood disorder that requires lifelong adherence to a
      complicated and burdensome medical regimen which could potentially impact
      emotional functioning of patients. The importance of understanding and promoting
      healthy emotional functioning is crucial not only to psychological well-being,
      but also to physical health as it has been shown to impact adherence to medical
      regimens [1-4]. The current study aimed to [1] determine the prevalence of
      depressive and anxiety symptoms in adolescent and adult patients with
      thalassemia; and [2] explore possible demographic, medical, and psychosocial
      correlates of these symptoms in 276 patients (14-58 years old, M age = 27.83; 52%
      female). Overall, most patients did not report experiencing significant symptoms
      of anxiety and depression (33% of participants indicated experiencing symptoms of
      anxiety and 11% symptoms of depression). Females and older patients were more
      likely to experience these symptoms than males and younger patients. Symptoms of
      anxiety and depression were positively associated with self-report of difficulty
      with adherence and negatively associated with quality of life. Given these
      findings, regular screening for anxiety and depression symptoms could help to
      identify at-risk individuals to provide them with appropriate psychological
      support with the goal of improving both emotional and physical health.

PMID- 20806233
TI  - Protein-protein docking with binding site patch prediction and network-based
      terms enhanced combinatorial scoring.
AB  - Protein-protein docking has made much progress in recent years, but challenges
      still exist. Here we present the application of our docking approach HoDock in
      CAPRI. In this approach, a binding site prediction is implemented to reduce
      docking sampling space and filter out unreasonable docked structures, and a
      network-based enhanced combinatorial scoring function HPNCscore is used to
      evaluate the decoys. The experimental information was combined with the predicted
      binding site to pick out the most likely key binding site residues. We applied
      the HoDock method in the recent rounds of the CAPRI experiments, and got good
      results as predictors on targets 39, 40, and 41. We also got good results as
      scorers on targets 35, 37, 40, and 41. This indicates that our docking approach
      can contribute to the progress of protein-protein docking methods and to the
      understanding of the mechanism of protein-protein interactions.

PMID- 20806234
TI  - Protein-protein docking benchmark version 4.0.
AB  - We updated our protein-protein docking benchmark to include complexes that became
      available since our previous release. As before, we only considered high
      resolution complex structures that are nonredundant at the family-family pair
      level, for which the X-ray or NMR unbound structures of the constituent proteins
      are also available. Benchmark 4.0 adds 52 new complexes to the 124 cases of
      Benchmark 3.0, representing an increase of 42%. Thus, benchmark 4.0 provides 176
      unbound-unbound cases that can be used for protein-protein docking method
      development and assessment. Seventeen of the newly added cases are enzyme
      inhibitor complexes, and we found no new antigen-antibody complexes. Classifying
      the new cases according to expected difficulty for protein-protein docking
      algorithms gives 33 rigid body cases, 11 cases of medium difficulty, and 8 cases
      that are difficult. Benchmark 4.0 listings and processed structure files are
      publicly accessible at http://zlab.umassmed.edu/benchmark/.

PMID- 20806235
TI  - Docking and scoring protein interactions: CAPRI 2009.
AB  - Protein docking algorithms are assessed by evaluating blind predictions performed
      during 2007-2009 in Rounds 13-19 of the community-wide experiment on critical
      assessment of predicted interactions (CAPRI). We evaluated the ability of these
      algorithms to sample docking poses and to single out specific association modes
      in 14 targets, representing 11 distinct protein complexes. These complexes play
      important biological roles in RNA maturation, G-protein signal processing, and
      enzyme inhibition and function. One target involved protein-RNA interactions not
      previously considered in CAPRI, several others were hetero-oligomers, or featured
      multiple interfaces between the same protein pair. For most targets, predictions
      started from the experimentally determined structures of the free (unbound)
      components, or from models built from known structures of related or similar
      proteins. To succeed they therefore needed to account for conformational changes
      and model inaccuracies. In total, 64 groups and 12 web-servers submitted docking
      predictions of which 4420 were evaluated. Overall our assessment reveals that 67%
      of the groups, more than ever before, produced acceptable models or better for at
      least one target, with many groups submitting multiple high- and medium-accuracy
      models for two to six targets. Forty-one groups including four web-servers
      participated in the scoring experiment with 1296 evaluated models. Scoring
      predictions also show signs of progress evidenced from the large proportion of
      correct models submitted. But singling out the best models remains a challenge,
      which also adversely affects the ability to correctly rank docking models. With
      the increased interest in translating abstract protein interaction networks into
      realistic models of protein assemblies, the growing CAPRI community is actively
      developing more efficient and reliable docking and scoring methods for everyone
      to use.

PMID- 20806236
TI  - Temperature effects on a doubly tethered diproline chiral stationary phase: Hold
      up volume, enantioselectivity and robustness.
AB  - Effect of temperature on hold-up volume, enantioselectivity and robustness of a
      novel doubly tethered diproline chiral stationary phase (CSP1) was studied. In
      column end-capping of residual silanol was utilized as a tool to exhibit in situ
      change of CSP1. The hold-up volume marker, 1,3,5-tri-tert-butylbenzene, was
      observed to be weakly retained (<1 s ) on a 5 cm*4.6 mm chiral column, and its
      retention time was changed with the carrier solvent and column temperature. The
      apparent thermodynamic parameters of 1,3,5-tri-tert-butylbenzene indicated an
      enthalpy-driven retention process with the hexane/isopropanol mobile phase, while
      an entropy-driven process with the hexane/methyl tert-butyl ether mobile phase.
      The DeltaDeltaH and DeltaDeltaS values of chiral separation for the four probes
      including 1,1'-bi-2-naphthol and warfarin were negative on CSP1. Nonlinear van't
      Hoff plots were observed for some analytes before and after the end-capping
      treatment. Depending on compound, end-capping strengthened or weakened the
      enantioseparation. Moreover, the enantioselectivity of CSP1 was shown to be
      robust by testing with heating-cooling cycles and step-temperature programs.

PMID- 20806237
TI  - Poly(N-vinylimidazole)-grafted capillary for electrophoresis prepared by surface
      initiated atom transfer radical polymerization.
AB  - A CE method for poly(N-vinylimidazole) (PVI)-grafted capillaries by the surface
      initiated atom transfer radical polymerization has been developed. The coating
      was prepared with N-vinylimidazole as the monomer, 2-bromo-2-methyl-N-[3
      (triethoxysilyl) propyl] propanamide (BTPAm) as the initiator and
      CuCl/CuCl(2)/2,2'-bipyridine as the catalyst and ligand. The direction and
      magnitude of EOF in the PVI-grafted capillary were investigated in a pH range of
      3.0-9.0. The results indicated that the EOF could be modulated by varying the pH
      value of the buffer and an anodic EOF was obtained at pH values below 6.5. A
      significant improvement in reproducibility and reduction of EOF appeared on the
      PVI-grafted capillary when compared with the uncoated capillary. Furthermore, the
      polymer coated capillaries were applied to the separations of the inorganic
      anions, organic acids and basic proteins and baseline separations were achieved
      with short analysis time and high reproducibility.

PMID- 20806238
TI  - Physical characterization and evaluation of HPLC columns packed with
      superficially porous particles.
AB  - Two HPLC columns packed with superficially porous packing material (KinetexTM 1.7
      and 2.6 MUm C18 particles) were evaluated in terms of their physical properties
      and performance characteristics. These columns were compared to a column packed
      with a sub-2 MUm totally porous material and to a Halo(TM) column packed with 2.7
      MUm C18 superficially porous packing. The columns packed with superficially
      porous particles displayed a comparably narrower size distribution, which is
      narrower than the distribution of the totally porous sub-2 MUm particles.
      Physical characteristics of the KinetexTM particles were evaluated in terms of
      surface area, pore diameter, and specific pore volume. Total, external, internal,
      and shell porosities among the four different columns were evaluated and
      compared. The specific permeability for the KinetexTM columns showed values close
      to those predicted by the Kozeny-Carman equation. All four columns were evaluated
      in terms of their chromatographic performance and compared using the Knox
      equation. The columns packed with the 2.6 and 2.7 MUm superficially porous
      materials showed reduced plate heights below 2, whereas the sub-2 MUm particles
      showed values of 2.2 and above.

PMID- 20806239
TI  - Chromatographic behavior of a new hybrid type RP material containing silica
      bonded 1,3-alternate 25,27-bis-[cyanopropyloxy]-26,28-bis-[3-propyloxy]
      calix[4]arene.
AB  - A novel 1,3-alternate 25,27-bis-[cyanopropyloxy]-26,28-bis-[3-propyloxy]
      calix[4]arene-bonded silica gel stationary phase (CalixPrCN) was prepared and its
      structure was confirmed by ATR-FTIR spectroscopy and elemental analysis. The
      CalixPrCN phase was characterized in terms of its surface coverage, hydrophobic
      selectivity, aromatic selectivity, shape selectivity, hydrogen bonding capacity,
      residue metal content, and silanol activity based on Tanaka, Lindner, and SMR 870
      test protocols. The effect of the acetonitrile content on the retention and
      selectivity of the selected neutral, basic, and acidic solutes was studied. The
      neutral and acidic analytes exhibited classical RP behavior, in which retention
      time decreases with increasing acetonitrile content. In contrast, basic analytes
      showed an increase in retention at low and high percentages of acetonitrile,
      forming "U-shaped" retention profiles. The new calixarene phase was compared with
      previously reported 1,3-alternate 25,27-bis-[propyloxy]-26,28-bis-[3-propyloxy]
      calix[4]arene stationary phase and commercial cyanopropyl column. The results
      indicate that the CalixPrCN stationary phase behaves like RP packing; however,
      inclusion complex formation, dipole-dipole, and pi-pi interactions seem to be
      involved in the separation process. The selectivity of this phase was
      demonstrated in separation of polynuclear aromatic hydrocarbons, non-steroidal
      anti-inflammatory drugs, and sulfonamides as analytes.

PMID- 20806240
TI  - New HPLC-chemometric approaches to the analysis of isoflavones in Trifolium
      lucanicum Gasp.
AB  - New HPLC-chemometric approaches were proposed for the simultaneous
      chromatographic quantification of daidzein, genistein, formononetin, and
      biochanin A in the samples consisting of the aerial parts of Trifolium lucanicum
      Gasp. (Leguminosae). Partial least squares and principal component regression
      algorithms were applied to the multiple chromatographic data set obtained by
      measuring at 240, 248, 256, and 264 nm to construct HPLC-partial least squares
      and HPLC-principal component regression calibrations. Chromatographic separation
      was carried out by using a mobile phase containing methanol, acetate buffer
      (pH=4.75) and acetonitrile (21:58:21, v/v/v) on the reversed phase column,
      SupelcosilTM LC-18 (15 cm*4.6 mm id). In addition, conventional HPLC based on the
      detection at a single wavelength was used for the determination of each compound
      in the extracts of T. lucanicum. The validity and applicability of the proposed
      HPLC-chemometric and conventional HPLC methods were performed by analyzing
      various synthetic plant samples. A good agreement was observed in the application
      of the proposed HPLC-chemometric tools to the synthetic and extracted samples of
      T. lucanicum.

PMID- 20806241
TI  - Analysis of Aloe-based phytotherapeutic products by using nano-LC-MS.
AB  - This article proposes a chromatographic method for the analysis of extracts of
      Aloe plants. The method was developed with a laboratory assembled nano-LC system
      coupled with a UV detector, followed by an IT-mass spectrometer. With a step
      gradient mode of ACN/H(2)O mixtures and employing a capillary column packed with
      C(18) (100 MUm id), a complete separation of the following anthrones was
      achieved: aloin (in its two isomeric forms A and B), 5-hydroxyaloin and 7
      hydroxyaloin (in its two isomeric forms A and B). The optimized nano-LC-MS method
      was validated for the quantification of aloin, the main component of Aloe with
      known pharmacological activities. RSD values obtained for retention time and peak
      areas were 1.3 and 12.1%, respectively. LOD and LOQ values of 0.4 and 1.5 MUg/mL
      were obtained for each aloin isomer. The method was applied to the analysis of
      Aloe vera and A. ferox extracts in order to acquire a fingerprint, characteristic
      for each plant. Several phenolic compounds were detected by UV and identified by
      MS. A. vera and A. ferox showed different profiles and it was possible to
      discriminate them. Several commercial formulations, declared to contain Aloe
      extracts, were analyzed. Comparing their chromatograms with those obtained from
      A. vera and A. ferox, it was possible to recognize the Aloe species and to
      determine aloin.

PMID- 20806242
TI  - Difference and variation of the sef14 operon gene clusters in Salmonella
      pullorum.
AB  - SEF14 fimbriae are only found in some strains of serogroup-D Salmonella such as
      S. enteritidis, suggesting that SEF14 fimbriae may affect serovar-specific
      virulence traits. In this study, we found that prevalence of sefA, sefD and sefR
      genes in S. dublin and S. enteritidis was 100%. In 18 isolates of S. pullorum,
      the prevalence of sefA gene was 100%, while the prevalence of sefD and sefR genes
      was 38.9% (7/18), and 11 strains isolated after 1980s did not contain any gene
      sefD or sefR. Interestingly, among the 7 strains of S. pullorum before 1980s, the
      sefD sequence has a missing base pair at position 196 and caused open reading
      frame (ORF) shift, resulting in a stop codon (TAG) at position 71 amino acid
      residual (Leu of TTA at position 214-216 shift into stop codon of TAG at position
      215-217). Unlike S. pullorum, all S. enteritidis and S. dublin tested could
      express SEF14 fimbriae in vitro.

PMID- 20806243
TI  - Characterization of an unusual cold shock protein from Staphylococcus aureus.
AB  - Of the three cold shock proteins expressed by Staphylococcus aureus, CspC is
      induced poorly by cold but strongly by various antibiotics and toxic chemicals.
      Using a purified CspC, here we demonstrate that it exists as a monomer in
      solution, possesses primarily beta-sheets, and bears substantial structural
      similarity with other bacterial Csps. Aggregation of CspC was initiated rapidly
      at temperatures above 40  degrees C, whereas, the Gibbs free energy of
      stabilization of CspC at 0 M GdmCl was estimated to be +1.6 kcal mol(-1),
      indicating a less stable protein. Surprisingly, CspC showed stable binding with
      ssDNA carrying a stretch of more than three thymine bases and binding with such
      ssDNA had not only stabilized CspC against proteolytic degradation but also
      quenched the fluorescence intensity from its exposed Trp residue. Analysis of
      quenching data indicates that each CspC molecule binds with ~5 contiguous thymine
      bases of the above ssDNA and binding is cooperative in nature.

PMID- 20806244
TI  - Inorganic binding peptide-mediated immobilization based on baculovirus surface
      display system.
AB  - The biomolecule-mediated assembly of novel composites has been the subject of
      numerous investigations during the last years, providing new insights into
      material science and engineering. Via molecular biology technology, we were able
      to introduce the genetically engineered polypeptide for inorganics (GEPI) as a
      molecular binder into biomolecules such as phage viruses, to assemble hybrid
      functional nanoarchitectures. In the present work, we introduced a novel
      nanocomposite comprising the Autographa californica nuclear polyhedrosis virus
      (AcNPV) and nanoparticles bound to it. Our results show that a GEPI-encoding gene
      was successfully introduced by recombination into a eukaryotic expression bacmid
      and finally displayed outside of the AcNPV after transfection into Sf9 insect
      cells using the Bac-to-Bac baculovirus expression system. The recombinant
      baculovirus maintained both the viral infectivity and the specific binding
      activity of the GEPI. The construction of the gene in the recombinant plasmid was
      examined by polymerase chain reaction analysis and enzymatic digestion
      identification, and verified by gene sequencing. Surface display of the fused
      peptide was revealed by Western blot analysis in dissolution studies and
      determined by immuno- gold electron microscopy. Adherence of nanoparticles to the
      recombinant baculovirus was visualized by transmission electron microscopy
      analysis. Here, we demonstrated the possibilities of combining peptide-mediated
      immobilization with baculovirus surface display technology.

PMID- 20806245
TI  - Molecular characterization of uropathogenic and diarrheagenic Escherichia coli
      pathotypes.
AB  - In this study diarrheagenic and uropathogenic Escherichia coli (UPEC) strains
      were comparatively characterized according to serotype, hemolytic activity,
      protein polymorphism among housekeeping enzymes, phylogenetic group and
      urovirulence genes. Intra-serogroup/serotype variations were observed. Hemolytic
      activity was detected in 100%, 93%, 67% and 39% of UPEC, EAEC, EPEC and ETEC
      strains, respectively. The alpha-hemolytic phenotype was observed in all
      pathogenic groups while beta-hemolytic phenotype was less frequent. PCR
      phylotyping revealed higher prevalence of diarrheagenic E. coli in groups A and D
      while uropathogenic strains were mainly found in subgroup B2. Amplification
      assays revealed that 74%, 45% and 22% of UPEC, EAEC and EPEC strains,
      respectively, carried at least one of the urovirulence sequences. The molecular
      typing system revealed a pathotype-specific clonal group distribution and showed
      a closer relationship between the EAEC and UPEC. Additionally, the occurrence of
      urovirulence traits, especially those related to iron acquisition, was more
      frequent among EAEC and UPEC than among the other E. coli pathotypes. This
      observation is of special value considering that the EAEC pathotype constitutes
      an emerging group of enteropathogens, particularly, in developing countries, and
      information on their pathogenic and phylogenetic characteristics is still scarce.

PMID- 20806246
TI  - Transcription factor Stb5p is essential for acetaldehyde tolerance in
      Saccharomyces cerevisiae.
AB  - Transcription factor Stb5p, previously known as one of the multidrug resistance
      gene regulators in Saccharomyces cerevisiae, was shown here to play an essential
      role in acetaldehyde tolerance. A mutant strain, Deltastb5 exhibited increased
      acetaldehyde sensitivity, and failed to induce genes such as GND1, TKL1 and TAL1
      involved in the pentose phosphate pathway (PPP) upon acetaldehyde stress. Using
      this strain it was revealed that Stb5p acts as a repressor for PGI1 encoding
      glucose-6-phosphate isomerase under acetaldehyde stress. In reverse, over
      expression of Stb5p reinforced acetaldehyde tolerance to the yeast. Furthermore,
      various deletion mutants of the genes involved in glycolysis showed increased
      acetaldehyde tolerance compared to the wild-type strain. From these results, it
      was suggested that Stb5p participates in acetaldehyde tolerance by regulating
      expression of the PPP genes and PGI1, and that down-regulation of glycolytic
      pathway may lead to vitalization of PPP and to increased acetaldehyde tolerance.

PMID- 20806247
TI  - Mutation of iceA in Helicobacter pylori compromised IL-8 induction from human
      gastric epithelial cells.
AB  - IceA of Helicobacter pylori (H. pylori) has been suggested as a virulence factor
      for the bacteria, but its pathogenic role remains unelucidated. Here, we examined
      the effect of iceA mutation on the secretion of IL-8 by human gastric epithelial
      cells. We also investigated whether the changes in IL-8 production caused by iceA
      mutation were associated with impaired adherence of H. pylori to the epithelial
      cells or with impaired apoptosis of these cells. The iceA mutant strain was
      constructed from wildtype H. pylori strain by insertional mutagenesis of iceA.
      The human gastric epithelial cells SGC7901 were infected with wildtype or mutant
      H. pylori for appropriate lengths of time. The adherence of the bacteria to the
      epithelial cells was examined by fluorescent microscopy using an anti-H. pylori
      antibody and flow cytometry. The apoptosis of the epithelial cells was studied by
      annexin-V staining and flow cytometry. The production of IL-8 by SGC 7901 cells
      was determined by ELISA. We found that iceA mutation was associated with
      significantly impaired production of IL-8 from the epithelial cells, which was
      not due to impaired adherence by the bacteria to the epithelial cells as wildtype
      and mutant H. pylori exhibited similar levels of binding to the epithelial cells.
      Furthermore, inactivation of iceA did not affect the apoptotic cell death of
      SGC7901. Our findings indicate that iceA may contribute to the pathogenicity of
      H. pylori by modulating the production of IL-8 by host epithelial cells.

PMID- 20806248
TI  - Prokaryotic diversity of a non-sulfide, low-salt cold spring sediment of Shawan
      County, China.
AB  - The prokaryotic diversity of a non-sulfide, low-salt cold spring sediment was
      investigated by constructing bacterial and archaeal clone libraries of the 16S
      rRNA gene. 241 bacterial clones were screened, which could be grouped into 86
      ribotypes, based on restriction fragment length polymorphism (RFLP) analysis.
      These were divided into 11 phyla (Actinobacteria, Acidobacteria, Bacteroidetes,
      Chlorobi, Cyanobacteria, Firmicutes, Gemmatimonadetes, Nitrospirae,
      Proteobacteria, Planctomycetes and Verrucomicrobia). Of these, Acidobacteria and
      Proteobacteria were the most dominant, representing 48% and 25% of the total
      bacteria clone library, respectively. For the archaeal clone library, 121
      positive clones were screened and 22 ribotypes were determined. BLAST analysis
      indicated that all ribotypes were affiliated with the phylum Crenarchaeota.
      Phylogenetic analysis classified them into three subgroups (Groups I-III). Groups
      I and III, belonging to the Soil-Freshwater-subsurface group and Marine group I,
      respectively, were the dominant groups, representing 50% and 47% of the library,
      respectively. Of them, 20% of ribotypes were related to the cold-loving
      Crenarchaeota. These findings show that bacteria in spring sediments are more
      diverse than are archaea; in addition, the spring harbors a large number of novel
      bacterial and archaeal species and maybe exist novel lineages.

PMID- 20806249
TI  - Applying target region amplification polymorphism markers for analyzing genetic
      diversity of Lentinula edodes in China.
AB  - The target region amplification polymorphism (TRAP) technique was utilized for
      assessing the genetic diversity of 55 wild strains and one cultivated strain of
      Lentinula edodes in China. From these strains, 932 DNA fragments were amplified
      using 12 primer combinations, 929 fragments (99.68%) of which were polymorphic
      between two or more strains. The average coefficient of pairwise genetic
      similarity was 0.696, within a range from 0.503 to 0.947. Cluster analysis and
      principal coordinate analysis separated the tested strains of L. edodes into two
      major groups. Group A was further divided into seven subgroups. In most cases,
      the strains from the same or adjoining regions could be preferentially clustered
      into small groups. The results from the average genetic similarity and the
      weighted average value of Shannon's Information Index among the tested strains of
      L. edodes from the same region revealed a vast genetic diversity in the natural
      germplasm found in China. Compared with the L. edodes strains from other regions,
      those found on the Yunnan Plateau, in the Hengduanshan Mountains, in Taiwan,
      South China, and Northeast China showed greater genetic diversity. The results of
      the present study indicated that the wild strains of L. edodes in China possessed
      abundant genetic variation, and the genetic relationships among them were highly
      associated with the geographic distribution. This is the first report
      demonstrating that TRAP markers were powerful for analyzing the genetic diversity
      of L. edodes, and the study lays the foundation for a further application of this
      remarkable technique to other fungi.

PMID- 20806250
TI  - Growth temperature associated protein expression and membrane fatty acid
      composition profiles of Salmonella enterica serovar Typhimurium.
AB  - Total cellular proteins and fatty acid composition profiles of mid-log phase
      cells of Salmonella enterica serovar Typhimurium grown at 8, 25, 37 or 42 
      degrees C were separated by 2D-PAGE and FAME analysis. Growth temperature
      associated protein expression can be grouped into 3 thermal classes which include
      proteins whose expression is: I) optimal at 37  degrees C, meaning their
      expression peaked at 37  degrees C; II) up-regulated with an increase in growth
      temperature; III) down-regulated with increase in growth temperature; meaning
      their expression peaked at 8  degrees C. At higher growth temperatures, proteins
      belonging to the functional groups of amino acid transport and metabolism,
      nucleotide metabolism, energy metabolism and post-translation modifications
      (chaperones) are present in substantially higher amounts. This increase in
      abundance is regulated in a temperature dependent manner. It is important to
      point out that proteins involved in energy metabolism observed in higher amounts
      at higher growth temperatures all belong to the glycolysis pathway, while at 8 
      degrees C they belonged to the TCA cycle. Increase in growth temperatures results
      in a decrease in membrane fatty acid unsaturation and an increase in saturated
      and cyclic fatty acids. These results provide an insight into the dynamic
      molecular and physiological responses of Salmonella Typhimurium during growth at
      different temperatures.

PMID- 20806251
TI  - Purification and characterization of the ncgl2923 -encoded 3-hydroxybenzoate 6
      hydroxylase from Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum ATCC 13032 metabolizes 3-hydroxybenzoate via
      gentisate. We have now characterized the ncgl2923 -encoded 3-hydroxybenzoate 6
      hydroxylase involved in the initial step of 3-hydroxybenzoate catabolism by this
      strain, a first 3-hydroxybenzoate 6-hydroxylase molecularly and biochemically
      characterized from a Gram-positive strain. The ncg12923 gene from Corynebacterium
      glutamicum ATCC 13032 was shown to encode 3-hydroxybenzoate 6-hydroxylase, the
      enzyme that catalyzes the NADH-dependent conversion of 3-hydroxybenzoate to
      gentisate. Ncgl2923 was expressed with an N-terminal six-His tag and purified to
      apparent homogeneity by Ni2(+)-nitrilotriacetic acid affinity chromatography. The
      purified H6-Ncgl2923 showed a single band at apparent molecular mass of 49 kDa on
      a sodium dodecyl sulfate polyacrylamide gel electrophoresis and was found to be
      most likely a trimer as determined by gel filtration chromatography. It had a
      specific activity of 6.92 +/- 0.39 U mg-1 against 3-hydroxybenzoate and with a
      K(m) value of 53.4 +/- 4.7 MUM using NADH as a cofactor. The product formed from
      the 3-hydroxybenzoate hydroxylation catalyzed by H6-Ncgl2923 was identified by
      high-performance liquid chromatography as gentisate, a ring-cleavage substrate in
      the microbial aromatic degradation. The enzyme exhibited a maximum activity at pH
      7.5 in phosphate buffer, and adding flavin adenine dinucleotide to a final
      concentration of 15 MUM would enhance the activity by three-fold. Although this
      enzyme shares no more than 33% identity with any of reported 3-hydroxybenzoate 6
      hydroxylases from Gram-negative bacterial strains, there is little difference in
      subunit sizes and biochemical characteristics between them.

PMID- 20806252
TI  - Molecular diversity of native rhizobia trapped by five field pea genotypes in
      Indian soils.
AB  - Five pea cultivars; HFP 4, HVP 3-5, HFP 9426, Jayanti and Hariyal, being grown in
      CCS Haryana Agricultural University farm were used to isolate native rhizobia.
      Selected 54 rhizobia, from all cultivars, were authenticated as rhizobia by plant
      infectivity test. Along with nodulation, symbiotic effectiveness in terms of
      symbiotic ratios showed wide range of effectiveness of pea rhizobia from 1.11 to
      5.0. DNA of all the 54 rhizobia was extracted and amplified by PCR, using ERIC
      and 16S rDNA primers. Dendrogram based on ERIC profiles of these 54 rhizobia
      showed the formation of 13 subclusters at 80% level of similarity. Dendrogram
      based on RFLP of 16S rDNA by three restriction endonucleases; Msp I, Csp 6I and
      Rsa I; also formed 13 subclusters at 80% level of similarity. However,
      positioning of subclusters was different from that of ERIC based dendrogram.
      Majority of the isolates i.e. 64.8% by ERIC profiles and 44.4% by RFLP of 16S
      rDNA formed one cluster. Isolates from same nodule were not 100% similar.
      Considering each cluster representing a rhizobial genotype, both techniques used
      to assess molecular diversity indicated the presence of 13 genotypes of field pea
      rhizobia in CCS Haryana Agricultural University farm soil. Two pea rhizobial
      genotypes were able to nodulate all the five pea cultivars. Furthermore, high
      strain richness index (0.43-0.5) of field pea rhizobia was observed by both the
      techniques.

PMID- 20806253
TI  - Validation of nested PCR and a selective biochemical method as alternatives for
      mycoplasma detection.
AB  - Direct culture is the most common way to reliably detect mycoplasma, but it is
      not practical for the qualitative control of cell therapeutics because of the
      elaborate culture medium, the prolonged incubation time, and the large sample
      volumes. Here, we chose two alternative methods using commercial detection kits,
      the PCR mycoplasma detection kit with nested PCR and the selective biochemical
      method, MycoAlert((r)), and validated them with the direct culture method as a
      reference. We tested eight mycoplasma species and five validation parameters:
      specificity, detection limit, robustness, repeatability, and ruggedness, based on
      the regulatory guidelines in the US Pharmacopoeia. All experiments were performed
      using fibroblasts spiked with mycoplasma. Specificity tests for both methods
      included all mycoplasma species, except Mycoplasma pneumonia and M. genitalium
      for the nested PCR and Ureaplasma urealyticum for the MycoAlert((r)) assay.
      Regarding the detection limit, the nested PCR proved to be as sensitive as the
      direct culture method and more sensitive than the MycoAlert((r)) assay. The
      predicted median for probit = 0.9 was 54 (44-76) CFU/ml for M. hyorhinis and 16
      (13-23) CFU/ml for M. hominis by the nested PCR, but 431 (346-593) CFU/ml and 105
      (87-142) CFU/ml, respectively, with MycoAlert((r)). Changes in the concentration
      of reagents, reagent lot, or individual analysts did not influence the results of
      the examined methods. The results of this study support nested PCR as a valuable
      alternative for mycoplasma detection.

PMID- 20806254
TI  - Optimization of laccase production by Pleurotus ostreatus IMI 395545 using the
      Taguchi DOE methodology.
AB  - Production of laccase using a submerged culture of Pleurotus orstreatus IMI
      395545 was optimized by the Taguchi orthogonal array (OA) design of experiments
      (DOE) methodology. This approach facilitates the study of the interactions of a
      large number of variables spanned by factors and their settings, with a small
      number of experiments, leading to considerable savings in time and cost for
      process optimization. This methodology optimizes the number of impact factors and
      enables to calculate their interaction in the production of industrial enzymes.
      Eight factors, viz. glucose, yeast extract, malt extract, inoculum, mineral
      solution, inducer (1 mM CuSO4) and amino acid (l-asparagine) at three levels and
      pH at two levels, with an OA layout of L18 (21 * 37) were selected for the
      proposed experimental design. The laccase yield obtained from the 18 sets of
      fermentation experiments performed with the selected factors and levels was
      further processed with Qualitek-4 software. The optimized conditions shared an
      enhanced laccase expression of 86.8% (from 485.0 to 906.3 U). The combination of
      factors was further validated for laccase production and reactive blue 221
      decolorization. The results revealed an enhanced laccase yield of 32.6% and dye
      decolorization up to 84.6%. This methodology allows the complete evaluation of
      main and interaction factors.

PMID- 20806255
TI  - Optimization of a genome-walking method to suit GC-rich template DNA from
      biotechnological relevant Actinobacteria.
AB  - SiteFinding-PCR has been recently reported to be a useful technique in order to
      identify unknown DNA fragments located adjacent to available sequences. However,
      this method has so far only been applied to few DNA sources including plants,
      samples from bioleaching communities, and a Pseudomonas strain. In order to
      complete the sequence information of two gene clusters in Gram-positive
      rhodococci the original protocol was applied yielding amplicons of insufficient
      size. The binding site of the previously published SiteFinder-2 oligo proved to
      be unsuitable for Rhodococcus and other members of the Actinobacteria since the
      binding motif occurred too frequently. Available genome sequences of different
      Actinobacteria were analysed and the binding site of the SiteFinder oligo
      modified. Moreover, PCR conditions were adapted to the high GC content of the
      template DNA allowing the successful adaptation of this method to two members of
      the Actinobacteria.

PMID- 20806256
TI  - Mutual influence of soil basidiomycetes and white mustard plants on their
      enzymatic and catabolic activities.
AB  - Liquid and volatile emanations in interactions of soil basidiomycetes with herbs
      affect fungal oxidoreductases and stress-related plant peroxidases (PO). In this
      study, gnotobiotic co-cultures between 6 non-pathogenic saprobes and 2
      ectomycorrhizal basidiomycetes with the non-host plant white mustard were
      established on glucose-salt medium with the respective controls. Determined were
      oxidoreductase activities for culture fluids and plant tissues at initial fungal
      idiophase and degradation rates of Remazol-BBR and 5 PAHs. In culture fluids of
      Agaricus arvensis, A. porphyrizon, Lepista nebularis, Stropharia rugoso-annulata,
      and Hypholoma fasciculare (group-5), the laccase-deficient plant enabled activity
      increases in fungal laccase (by 2300-fold), in extracellular (fungal and?) plant
      derived peroxidases (by 21-fold), and in the dissipation of phenanthrene and
      anthracene. Oxidative activities in roots rose by 46000-fold during adsorption of
      fungal laccases. Increases in the stress-related shoot-PO (by 4.1-fold) were
      exclusively elicited by group-5 saprobes and correlated with plant-phenolic
      mediated formations of Mn(III) and increases in Remazol BBR bleaching. Agaricus
      bisporus and the ectomycorrhizal Hebeloma crustuliniforme and Suillus granulatus
      did not respond to plant emanations with elevated laccase activities but
      solubilized apparently root-surface PO. They failed to elicit stress-related
      activity increases of PO in white mustard shoot and prevented Mn(III) formation
      in several tissues. It is concluded that white mustard emanations promoted the
      catabolic performance of the plant-stress eliciting group-5 saprobes but not of
      A. bisporus and the ectomycorrhizal fungi with their low stress-inducing
      potential. The nature of the plant-released stimuli and the classes of fungus
      released stress agents discussed must be determined in further studies.

PMID- 20806257
TI  - Purification of a toxic cysteine protease produced by pathogenic Aeromonas
      hydrophila isolated from rainbow trout.
AB  - An extracellular lethal toxin produced by Aeromonas hydrophila strain RT860715K
      originally isolated from diseased rainbow trout (Oncorhynchus mykiss) was
      purified by using Fast Protein Liquid Chromatography system with hydrophobic
      interaction chromatography and anion exchange columns. The toxin was a cysteine
      protease, inhibited by L -cysteine, iodoacetic acid, N -ethylamleimide, P
      chloromercuibenzene-sulfonic acid and N-alpha-p-tosyl-1-lysine-chloromethyl
      ketone (TLCK), and showed maximal activity at pH 6.0. The molecular weight of the
      purified enzyme proved to be 94 kDa as estimated by SDS-PAGE. In addition, the
      toxin was also completely inhibited by HgCl(2) but partially inhibited by
      ethylenediamine tetraacetic acid (EDTA) and CuCl2. Both the extracellular
      products of Aeromonas hydrophila RT860715K and the purified protease were lethal
      to rainbow trout (weighing 18 g) with LD50 values of 2.87 and 0.93 MUg protein g
      1 fish body weight, respectively. The addition of L-cysteine completely inhibited
      the lethal toxicity of the purified protease, indicating that this cysteine
      protease was a lethal toxin produced by the bacterium.

PMID- 20806259
TI  - Vancomycin-resistant enterococci from Portuguese wastewater treatment plants.
AB  - The objective of this study was to evaluate the incidence of vancomycin resistant
      enterococci in sludge and sewage of urban and poultry-slaughterhouse wastewater
      treatment plants. A total of 17 vancomycin resistant enterococci (eight vanA 
      containing Enterococcus faecium and nine vanC1/vanC2 -containing Enterococcus
      gallinarum/casseliflavus) were found among 499 isolates of sewage and sludge
      samples of 14 urban and nine poultry-slaughterhouse wastewater treatment plants.
      These seventeen VRE isolates showed resistance to kanamycin (n = 8), tetracycline
      (n = 7), erythromycin (n = 7), ciprofloxacin (n = 7), ampicillin (n = 7),
      streptomycin (n = 6), and gentamicin (n = 2). The tetM gene, related with
      tetracycline resistance, was found in six of eight van A-containing isolates, in
      all seven vanC-1 isolates and in one of two vanC-2 isolates. The ermB gene in
      seven erythromycin-resistant isolates; and the aac6 '-aph2 " gene in the two high
      level-gentamicin-resistant isolates. Moreover, two vanA -containing E. faecium
      isolates harbored the hyl virulence gene, and three isolates the entA bacteriocin
      gene. The purK-1 allele was detected in our urban vanA -containing E. faecium
      isolate, and we found as well the purK-6 allele in one poultry-slaughterhouse
      vanA -containing E. faecium isolate. This study suggests that the wastewater
      treatment plants might be an important source of dissemination of antibiotic
      resistant enterococci in Portugal.

PMID- 20806258
TI  - Water-soluble red pigments from Isaria farinosa and structural characterization
      of the main colored component.
AB  - The present study describes the red pigment synthesized by the filamentous fungi
      Isaria farinosa under submerged culture conditions. The pigment production was
      optimal under the following conditions: pH 5, agitation speed 150 rpm,
      temperature 27  degrees C, incubation time 192 h, light source total darkness,
      sucrose and glucose as carbon source, yeast extract, meat peptone and monosodium
      glutamate at a fixed concentration of 3% as nitrogen source. The addition of 10
      mM CaCl2 to the culture medium increased the biomass and pigment production.
      Structural elucidation of the pigment using gas chromatography-mass spectrometry,
      Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance
      spectroscopy revealed that the red pigment contains an anthraquinone-related
      compound. In addition, the isolated pigment was water soluble, and was stable
      when exposed to salt solution (96.1% of stability after treatment with sodium
      chloride), acid (72.1% with citric acid), heat (86.2% at 60  degrees C), and
      sunlight (99.4%). These results are promising to further exploit the fungal
      culture of Isaria farinosa for producing the red pigment and, subsequently, to
      considerably increase its yield. The study has commercial importance in the
      production of Isaria farinosa pigment for industrial application after
      considerable toxicological examination.

PMID- 20806260
TI  - Isolation and characterization of an extremely long tail Thermus bacteriophage
      from Tengchong hot springs in China.
AB  - Thermus strains are regarded as models to investigate the mechanism of
      thermostability of thermophiles, and phages from Thermus are particularly
      interesting because of their way to regulate gene expression. In this research, a
      Thermus bacteriophage named TSP4 (Thermus Siphoviridae phage) was isolated from
      Tengchong hot springs in China, and characteristics of morphology, temperature
      for phage production, pH and organic solvent sensitivity, DNA restriction
      endonuclease digestion and protein composition of TSP4 were further studied. TSP4
      belonged to the Siphoviridae family and had a hexagonal head of 73 nm in
      diameter, an extremely long and flexible tail of 785 nm in length and 10 nm in
      width. TSP4 was very stable at 65  degrees C and pH 7.6. The capsid was
      apparently devoid of lipid. By SDS-PAGE, six protein bands were found in purified
      virions. Despite their exceptional habitats separated by thousands of kilometers,
      the characteristics of this thermophilic phage showed high similarity to Thermus
      siphoviruses P23-45 and P74-26 isolated from Kamchatka peninsula hot springs in
      the Far East, Russia.

PMID- 20806261
TI  - Intramolecular interactions of L-phenylalanine: Valence ionization spectra and
      orbital momentum distributions of its fragment molecules.
AB  - Intramolecular interactions between fragments of L-phenylalanine, i.e., phenyl
      and alaninyl, have been investigated using dual space analysis (DSA) quantum
      mechanically. Valence space photoelectron spectra (PES), orbital energy topology
      and correlation diagram, as well as orbital momentum distributions (MDs) of L
      phenylalanine, benzene and L-alanine are studied using density functional theory
      methods. While fully resolved experimental PES of L-phenylalanine is not yet
      available, our simulated PES reproduces major features of the experimental
      measurement. For benzene, the simulated orbital MDs for 1e(1g) and 1a(2u)
      orbitals also agree well with those measured using electron momentum spectra. Our
      theoretical models are then applied to reveal intramolecular interactions of the
      species on an orbital base, using DSA. Valence orbitals of L-phenylalanine can be
      essentially deduced into contributions from its fragments such as phenyl and
      alaninyl as well as their interactions. The fragment orbitals inherit properties
      of their parent species in energy and shape (ie., MDs). Phenylalanine orbitals
      show strong bonding in the energy range of 14-20 eV, rather than outside of this
      region. This study presents a competent orbital based fragments-in-molecules
      picture in the valence space, which supports the fragment molecular orbital
      picture and building block principle in valence space. The optimized structures
      of the molecules are represented using the recently developed interactive 3D-PDF
      technique.

PMID- 20806262
TI  - Artificial neural network-based drug design for diabetes mellitus using
      flavonoids.
AB  - Diabetes mellitus is a chronic metabolic disease involving the failure to
      regulate glucose blood levels in the body and has been linked with numerous
      detrimental complications. Studies have shown that these complications can be
      linked to the activities of aldose reductase (AR), an enzyme of the polyol
      pathway. Flavonoids have been identified as good AR inhibitors (ARIs) and are
      also strong antioxidants with radical scavenging (RS) activity. As such,
      flavonoids show potential to become a better class of ARIs because they are able
      to concurrently address the oxidative stress issue. In this article, we carried
      out quantitative structure-activity relationship analysis of flavones and
      flavonols (members of flavonoid family) using artificial neural networks. Three
      computer experiments were conducted to study the influence of hydrogen (H),
      hydroxyl (-OH), and methoxyl (-CH(3)) functional groups on eight substitution
      sites of the lead flavone molecule and to predict potential ARIs. Of 6561
      possible flavones and flavonols, in experiment 1, we predicted 69 potent ARIs,
      and in experiment 2, we predicted 346 compounds with strong RS activity. In
      experiment 3, we combined these results to find overlapping compounds with both
      strong AR inhibition and RS activity and we are able to predict 10 potent
      compounds with strong AR inhibition (IC(50) < 0.3 MUM) and RS activity (IC(25) <
      1.0 MUM). These 10 compounds show promise of being good therapeutic agents in the
      prevention of diabetic complications and is suggested to undergo further wet
      bench experimentation to prove their potency.

PMID- 20806263
TI  - CABS-NMR--De novo tool for rapid global fold determination from chemical shifts,
      residual dipolar couplings and sparse methyl-methyl NOEs.
AB  - Recent development of nuclear magnetic resonance (NMR) techniques provided new
      types of structural restraints that can be successfully used in fast and low-cost
      global protein fold determination. Here, we present CABS-NMR, an efficient
      protein modeling tool, which takes advantage of such structural restraints. The
      restraints are converted from original NMR data to fit the coarse grained protein
      representation of the C-Alpha-Beta-Side-group (CABS) algorithm. CABS is a Monte
      Carlo search algorithm that uses a knowledge-based force field. Its versatile
      structure enables a variety of protein-modeling protocols, including purely de
      novo folding, folding guided by restraints derived from template structures or,
      structure assembly based on experimental data. In particular, CABS-NMR uses the
      distance and angular restraints set derived from various NMR experiments. This
      new modeling technique was successfully tested in structure determination of 10
      globular proteins of size up to 216 residues, for which sparse NMR data were
      available. Additional detailed analysis was performed for a S100A1 protein.
      Namely, we successfully predicted Nuclear Overhauser Effect signals on the basis
      of low-energy structures obtained from chemical shifts by CABS-NMR. It has been
      observed that utility of chemical shifts and other types of experimental data
      (i.e. residual dipolar couplings and methyl-methyl Nuclear Overhauser Effect
      signals) in the presented modeling pipeline depends mainly on size of a protein
      and complexity of its topology. In this work, we have provided tools for either
      post-experiment processing of various kinds of NMR data or fast and low-cost
      structural analysis in the still challenging field of new fold predictions.

PMID- 20806264
TI  - A simulation strategy for the atomistic modeling of flexible molecules covalently
      tethered to rigid surfaces: application to peptides.
AB  - A computational strategy to model flexible molecules tethered to a rigid inert
      surface is presented. The strategy is able to provide uncorrelated relaxed
      microstructures at the atomistic level. It combines an algorithm to generate
      molecules tethered to the surface without atomic overlaps, a method to insert
      solvent molecules and ions in the simulation box, and a powerful relaxation
      procedure. The reliability of the strategy has been investigated by simulating
      two different systems: (i) mixed monolayers consisting of binary mixtures of long
      chain alkyl thiols of different lengths adsorbed on a rigid inert surface and
      (ii) CREKA (Cys-Arg-Glu-Lys-Ala), a short linear pentapeptide that recognizes
      clotted plasma proteins and selectively homes to tumors, covalently tethered to a
      rigid inert surface in aqueous solution. In the first, we examined the
      segregation of the two species in the monolayers using different long-chain:short
      chain ratios, whereas in the second, we explored the conformational space of
      CREKA and ions distribution considering densities of peptides per nm(2) ranging
      from 0.03 to 1.67. Results indicate a spontaneous segregation in alkyl thiol
      monolayers, which enhances when the concentration of longest chains increases.
      However, the whole conformational profile of CREKA depends on the number of
      molecules tethered to the surface pointing out the large influence of molecular
      density on the intermolecular interactions, even though the bioactive
      conformation was found as the most stable in all cases.

PMID- 20806265
TI  - Shaping white light through electroluminescent fully organic coupled
      microcavities.

PMID- 20806266
TI  - Graphoepitaxial assembly of symmetric block copolymers on weakly preferential
      substrates.

PMID- 20806267
TI  - Direct ethanol fuel cell using hydrotalcite clay as a hydroxide ion conductive
      electrolyte.
AB  - An alkaline-type direct ethanol fuel cell (DEFC) using a natural clay electrolyte
      with non-platinum catalysts is proposed. So-called hydrotalcite clay, Mg-Al
      layered double hydroxide intercalated with CO32-, is shown to be a hydroxide ion
      conductor. An alkaline-type DEFC using this natural clay as the electrolyte and
      aqueous solution of ethanol and potassium hydroxide as a source of fuel exhibits
      excellent electrochemical performance from room temperature to 80  degrees C.

PMID- 20806268
TI  - Holographic design and fabrication of diamond symmetry photonic crystals via dual
      beam quadruple exposure.

PMID- 20806269
TI  - ERAD ubiquitin ligases: multifunctional tools for protein quality control and
      waste disposal in the endoplasmic reticulum.
AB  - In eukaryotic cells terminally misfolded proteins of the secretory pathway are
      retarded in the endoplasmic reticulum (ER) and subsequently degraded in a
      ubiquitin-proteasome-dependent manner. This highly conserved process termed ER
      associated protein degradation (ERAD) ensures homeostasis in the secretory
      pathway by disposing faulty polypeptides and preventing their deleterious
      accumulation and eventual aggregation in the cell. The focus of this paper is the
      functional description of membrane-bound ubiquitin ligases, which are involved in
      all critical steps of ERAD. In the end we want to speculate on how the modular
      architecture of these entities ensures the specificity of substrate selection and
      possibly accomplishes the transport of misfolded polypeptides from the ER into
      the cytoplasm.

PMID- 20806270
TI  - The RNA dreamtime: modern cells feature proteins that might have supported a
      prebiotic polypeptide world but nothing indicates that RNA world ever was.
AB  - Modern cells present no signs of a putative prebiotic RNA world. However, RNA
      coding is not a sine qua non for the accumulation of catalytic polypeptides.
      Thus, cellular proteins spontaneously fold into active structures that are
      resistant to proteolysis. The law of mass action suggests that binding domains
      are stabilized by specific interactions with their substrates. Random polypeptide
      synthesis in a prebiotic world has the potential to initially produce only a very
      small fraction of polypeptides that can fold spontaneously into catalytic
      domains. However, that fraction can be enriched by proteolytic activities that
      destroy the unfolded polypeptides and regenerate amino acids that can be recycled
      into polypeptides. In this open system scenario the stable domains that
      accumulate and the chemical environment in which they are accumulated are linked
      through self coding of polypeptide structure. Such open polypeptide systems may
      have been the precursors to the cellular ribonucleoprotein (RNP) world that
      evolved subsequently.

PMID- 20806271
TI  - Design and synthesis of 2-phenoxynicotinic acid hydrazides as anti-inflammatory
      and analgesic agents.
AB  - A series of 2-phenoxynicotinic acid hydrazides were synthesized and evaluated for
      their analgesic and anti-inflammatory activities. Several compounds having an
      unsubstituted phenyl/4-pyridyl or C-4 methoxy substituent on the terminal phenyl
      ring showed moderate to high analgesic or anti-inflammatory activity in
      comparison to mefenamic acid as the reference drug. The compounds with highest
      anti-inflammatory activity were subjected to in vitro COX-1/COX-2 inhibition
      assays and showed moderate to good COX-1 and weak COX-2 inhibition activities.

PMID- 20806272
TI  - 1,3-diaryl-2-propenones and 2-benzylidene-1,3-indandiones: a quest for compounds
      displaying greater toxicity to neoplasms than normal cells.
AB  - A series of 1,3-diaryl-2-propenones 2a-j and analogous 2-benzylidene-1,3
      indandiones 3a-j were evaluated against various neoplasms and normal cells. In
      general, greater cytotoxic potencies and selective toxicity to human malignant
      cells were observed by the compounds in series 2 rather than 3. In particular, 2i
      emerged as a lead molecule having an average CC(50) figure of 8.6 uM and a
      selective index value of 18. Various physicochemical features of 2a-j were
      correlated with the cytotoxic potencies to neoplastic cell lines which provide
      guidelines for expansion of this series of compounds. The enone 2i induced
      internucleosomal DNA fragmentation and activated caspase-3 in HL-60 cells
      suggesting that one of the ways in which the cytotoxicity of the compounds in
      series 2 is mediated towards some of the cell lines used in this study is by
      apoptosis. Neurotoxicity in mice was generally lower in series 2 than 3a-j.

PMID- 20806274
TI  - Quality care in seniors with new-onset rheumatoid arthritis: a Canadian
      perspective.
AB  - OBJECTIVE: To estimate the percentage of seniors with rheumatoid arthritis (RA)
      receiving disease-modifying antirheumatic drugs (DMARDs) within the first year of
      diagnosis. METHODS: We assembled an incident RA cohort from Ontario physician
      billing data for 1997-2006. We used a standard algorithm to identify 24,942
      seniors with RA based on >= 2 billing codes >= 60 days apart but within 5 years.
      Drug exposures were obtained from pharmacy claims data. We followed subjects for
      1 year, assessing if they had been exposed (defined as >= 1 prescription) to 1 or
      more DMARDs within the first year of RA diagnosis. We assessed secular trends and
      differences for subjects who had received rheumatology care (defined as >= 1
      rheumatology encounter) versus those who had not. RESULTS: In total, only 39% of
      the 24,942 seniors with new-onset RA identified over 1997-2006 were exposed to
      DMARD therapy within 1 year of diagnosis. This increased from 30% in 1997 to 53%
      in 2006. Patients whose care involved a rheumatologist were more likely to be
      exposed to DMARDs than those who had no rheumatology care. In 2006, 67% of
      subjects receiving rheumatology care were exposed to DMARDs versus 21% of those
      with no rheumatology care. CONCLUSION: Improvements in RA care have occurred, but
      more efforts are needed. Subjects receiving rheumatology care are much more
      likely to receive DMARDs as compared to those with no rheumatology care. This
      emphasizes the key role of rheumatologists.

PMID- 20806273
TI  - Assessing physical activity in persons with knee osteoarthritis using
      accelerometers: data from the osteoarthritis initiative.
AB  - OBJECTIVE: Physical activity measured by accelerometers requires basic
      assumptions to translate the output into meaningful measures. We used
      accelerometer data from the Osteoarthritis Initiative to investigate in the
      context of knee osteoarthritis (OA) the following data processing assumptions
      derived from the general US adult population: nonwear (a period the monitor was
      removed), based on zero activity exceeding 60 minutes; and a valid day of
      monitoring, based on wear time evidence exceeding 10 hours. METHODS: We examined
      the influence of nonwear thresholds ranging from 20 to 300 minutes of zero
      activity on mean daily activity minutes (counts>0), mean daily activity counts,
      and mean daily moderate to vigorous physical activity minutes. The effect of
      selecting minimums of 8, 10, or 12 wear hours to signify a valid day of
      monitoring on data retention was examined. RESULTS: Our sample of 3,536 days of
      accelerometer data from 519 persons with knee OA showed that mean daily activity
      minutes increased with the nonwear threshold until stabilizing at 463 minutes per
      day, corresponding to the 90-minute nonwear threshold. Similar patterns were
      observed for mean daily activity counts. Varying the nonwear threshold had no
      effect on mean daily moderate to vigorous physical activity minutes. Choosing the
      90-minute nonwear threshold and a minimum of 10 wear hours to constitute a valid
      day provided 94% data retention. CONCLUSION: Data supported applying the 90
      minute nonwear threshold to the knee OA population instead of the 60-minute
      threshold for the general population, while retaining the 10-hour valid day
      threshold.

PMID- 20806275
TI  - Noodling and Mycobacterium marinum infection mimicking seronegative rheumatoid
      arthritis complicated by anti-tumor necrosis factor alpha therapy.

PMID- 20806276
TI  - Hearing loss, uveomeningitis, and stroke in a 55-year-old man.

PMID- 20806277
TI  - A cavernous hemangioma of the thyroid gland: First documentation by ultrasound of
      a rare pathology.
AB  - Hemangioma of the thyroid gland is an extremely rare condition. We report a case
      of a primary cavernous hemangioma in the left lobe of the thyroid gland in an 84
      year-old woman. Ultrasound examination of the lesion showed an inhomogeneous and
      hypoechoic nodule that was well demarcated from the rest of the left lobe and
      hypovascular on color Doppler ultrasound. Ultrasound-guided fine-needle
      aspiration was performed. The cytologic differential diagnosis included an
      anaplastic carcinoma of the thyroid gland. After hemithyroidectomy, the final
      diagnosis was a benign hemangioma of the thyroid gland.

PMID- 20806278
TI  - Therapeutic apheresis in special populations.

PMID- 20806279
TI  - Clinical applications of therapeutic apheresis.

PMID- 20806280
TI  - Building a new therapeutic apheresis service.

PMID- 20806281
TI  - Introduction and overview of therapeutic apheresis.

PMID- 20806282
TI  - Therapeutic Apheresis academy an educational compendium.

PMID- 20806283
TI  - Genotoxicity testing: moving beyond qualitative "screen and bin" approach towards
      characterization of dose-response and thresholds.
AB  - For more than 40+ years, genotoxicity data have been interpreted in a
      qualitative, binary mode; a chemical is considered either positive or negative
      for a response in the test system. Although dose-response information is
      sometimes used in this decision, it is not routine to obtain the amount of
      information needed to inform risk assessment, for example to determine no
      observed-genotoxic-effect-levels, primarily due to the historical view of
      genotoxic responses as "linear, no-threshold." Only recently have researchers
      begun to address this issue through robust experimental designs and application
      of statistical models. A growing body-of-evidence supports the existence of
      response thresholds for a number of mutagenic agents, in vitro and in vivo.
      Clearly, simple observation of a "hockey-stick" dose-response curve is not
      sufficient to establish a threshold. Collection of robust empirical data must be
      supported with an analysis of biological plausibility for the observed threshold.
      In this context, a chemical-specific mode-of-action (MOA) approach, which
      identifies key events responsible for the observed mutagenic effect, is extremely
      valuable. Biomarkers of key events, providing qualitative and quantitative
      information, can be integrated in a weight-of-evidence-based assessment of
      genotoxicity data from multiple test systems and used to identify data gaps to
      resolve/reduce uncertainties during the risk assessment process. To this end,
      specific recommendations on study design and data analysis are proposed. As the
      Environmental Mutagen Society celebrates its 40th anniversary, the field of
      genetic toxicology is marking a milestone on the path to a new paradigm, using a
      MOA, data-driven approach to answer questions about thresholds for genotoxic
      agents.

PMID- 20806284
TI  - Puerarin enhances adipocyte differentiation, adiponectin expression, and
      antioxidant response in 3T3-L1 cells.
AB  - Puerarin, a major isoflavone glycoside from Kudzu root (Pueraria lobata), has
      been reported to exert antihyperglycemic and antioxidant effects and thus have
      pharmacological actions in the treatment of diabetes and cardiovascular diseases.
      We investigated the effects of puerarin on the changes of key gene expression
      associated with adipocyte differentiation and insulin sensitivity and link to
      cellular antioxidant response pathways. Puerarin treatment significantly enhanced
      differentiation of 3T3-L1 preadipocytes accompanying increased lipid accumulation
      and glucose-6-phosphate dehydrogenase (G6PDH) activity. At a molecular level,
      puerarin upregulated mRNA expression of peroxisome proliferator-activated
      receptor gamma (PPARgamma) and its target genes, an adipocyte-specific fatty acid
      binding protein (aP2) and GLUT4. Puerarin also caused a significant increase in
      mRNA level of adiponectin, an important insulin-sensitizing adipocytokine that is
      downregulated in insulin-resistant and diabetic states. In addition, treatment
      with puerarin was found to upregulate mRNA levels of G6PDH, glutathione
      reductase, and catalase, all of which are important for endogenous antioxidant
      responses. These data suggest that the hypoglycemic effects of puerarin can be
      attributed to the upregulation of PPARgamma and its downstream target genes,
      GLUT4 and adiponectin expression, leading to increased glucose utilization.
      Puerarin may also be effective in preventing the rise of oxidative stress during
      adipocyte differentiation by increasing endogenous antioxidant responses.

PMID- 20806285
TI  - Influence of a low dose of dietary soybean on bone properties and mineral status
      in young rats.
AB  - The aim of this study was to evaluate effects of dietary supplementation with
      genistein, daidzein stachyose, and raw or cooked soybean on mineral content,
      optical density, and mechanical properties of bones in growing rats. The
      experiment was performed on 70 male young Wistar rats (4 weeks old at the start
      of the experiment) divided into seven groups. Genistein, daidzein, or stachyose
      were administered by gavage. Raw or cooked soybean was added directly to the diet
      (1%) The experiment lasted 28 days. Femurs were removed postmortem and kept until
      analysis at -20 degrees C. Mineral content in bones was determined by atomic
      absorption flame spectrometry, and inductively coupled plasma atomic emission
      spectrometry. Optical density was analyzed with a KODAK 1D 3.5 system. Mechanical
      properties were tested using INSTRON 4301 equipment. Genistein increased mineral
      content in bones of growing rats. Biological action of genistein and daidzein on
      the mineralization of bone tissues in growing rats was different. Addition of
      stachyose (1.9 mg/day/rat) did not affect bone tissues, nor did the addition of
      raw or cooked soybean. None of the studied biologically active substances:
      genistein (0.26 mg/day/rat), daidzein (0.104 mg/day/rat), stachyose (1.9
      mg/day/rat), or soybean had an effect on bone optical density.

PMID- 20806287
TI  - Professional and organizational commitment in paediatric occupational therapists:
      the influence of practice setting.
AB  - The professional and organizational commitment of paediatric occupational
      therapists working in two distinct practice settings, schools and medically based
      settings, was investigated. A web-based survey program was used to administer a
      questionnaire to occupational therapists employed in New York, New Jersey and
      Connecticut. The study employed social identity theory as a guiding perspective
      in understanding therapists' professional and organizational commitment. One
      hundred and fifty-seven paediatric therapists responded to the Professional
      Commitment Questionnaire and the Organizational Commitment Questionnaire to gauge
      their commitment to both the profession and their employing organizations.
      Results indicated that paediatric therapists, regardless of employment setting,
      have high professional commitment. Paediatric occupational therapists employed in
      medically based settings indicated statistically significant higher
      organizational commitment than their school-based counterparts. For therapists
      that work in school settings, the presence of a professional cohort did not
      influence professional commitment scores. As the study employed a web-based
      survey methodology, only individuals who were members of associations and had
      access to a computer and the Internet were able to participate. Further study
      might include widening the participant pool as well as adding additional
      instruments to explore both professional and organizational commitment on a more
      national scale.

PMID- 20806289
TI  - Alpha2beta1 integrin is the major collagen-binding integrin expressed on human
      Th17 cells.
AB  - Growing evidence indicates that collagen-binding integrins are important
      costimulatory molecules of effector T cells. In this study, we demonstrate that
      the major collagen-binding integrin expressed by human Th17 cells is alpha2beta1
      (alpha2beta1) or VLA-2, also known as the receptor for collagen I on T cells. Our
      results show that human naive CD4(+) T cells cultured under Th17 polarization
      conditions preferentially upregulate alpha2beta1 integrin rather than alpha1beta1
      integrin, which is the receptor for collagen IV on T cells. Double staining
      analysis for integrin receptors and intracellular IL-17 showed that alpha2
      integrin but not alpha1 integrin is associated with Th17 cells. Cell adhesion
      experiments demonstrated that Th17 cells attach to collagen I and collagen II
      using alpha2beta1 integrin but did not attach to collagen IV. Functional studies
      revealed that collagens I and II but not collagen IV costimulate the production
      of IL-17A, IL-17F and IFN-gamma by human Th17 cells activated with anti-CD3.
      These results identify alpha2beta1 integrin as the major collagen receptor
      expressed on human Th17 cells and suggest that it can be an important
      costimulatory molecule of Th17 cell responses.

PMID- 20806290
TI  - Inhibition of the alternative pathway of complement activation reduces
      inflammation in experimental autoimmune uveoretinitis.
AB  - We have shown previously that complement factor H (CFH) and complement factor B
      (CFB) are constitutively expressed by retinal pigment epithelial cells and their
      production is regulated by inflammatory cytokines, suggesting that the
      alternative pathway (AP) of complement activation might play a role in retinal
      inflammation. In this study, we further investigated the role of the AP in
      retinal inflammation using experimental autoimmune uveoretinitis (EAU) as a
      model. Mice with EAU show increased levels of C3d deposition and CFB expression
      in the retina. Retinal inflammation was suppressed clinically and histologically
      by blocking AP-mediated complement activation with a complement receptor of the
      Ig superfamily fusion protein (CRIg-Fc). In line with reduced inflammation, C3d
      deposition and CFB expression were markedly decreased by CRIg-Fc treatment.
      Treatment with CRIg-Fc also led to reduced T-cell proliferation and IFN-gamma,
      TNF-alpha, IL-17, and IL-6 cytokine production by T cells, and reduced nitric
      oxide production in BM-derived macrophages. Our results suggest that AP-mediated
      complement activation contributes significantly to retinal inflammation in EAU.
      CRIg-Fc suppressed retinal inflammation in EAU by blocking AP-mediated complement
      activation with probable direct effects on C3/C5 activation of macrophages, thus
      leading to reduced nitric oxide production by infiltrating CRIg(-) macrophages.

PMID- 20806291
TI  - Intraoperative hyperthermic intraperitoneal chemotherapy after cytoreductive
      surgery for peritoneal carcinomatosis in an experimental model.
AB  - BACKGROUND: The combination of cytoreductive surgery (CS) and hyperthermic
      intraperitoneal chemotherapy (HIPEC) is the treatment of choice for selected
      patients with peritoneal carcinomatosis (PC) of colorectal origin. However, it
      remains to be proven whether the addition of HIPEC to CS is essential for the
      reported survival benefit. METHODS: Sixty WAG/Rij rats were inoculated
      intraperitoneally with the rat colonic carcinoma cell line CC-531. Animals were
      randomized into three treatment groups: CS alone, CS followed by HIPEC (mitomycin
      15 mg/m(2) ) and CS followed by HIPEC (mitomycin 35 mg/m(2) ). Survival was the
      primary outcome parameter. RESULTS: The median survival of rats treated with CS
      alone was 43 days. Rats receiving HIPEC 15 mg/m(2) and HIPEC 35 mg/m(2) both had
      a significantly longer median survival of 75 days (P = 0.003) and 97 days (P <
      0.001) respectively. Rats receiving HIPEC showed a significantly lower tumour
      load at autopsy compared with rats treated with CS alone. CONCLUSION: A
      combination of CS and HIPEC results in longer survival than CS alone in rats with
      PC of colorectal origin.

PMID- 20806292
TI  - A non-redundant role for OX40 in the competitive fitness of Treg in response to
      IL-2.
AB  - OX40 stimulation is known to enhance activation of effector T cells and to
      inhibit induction and suppressive function of Treg. Here we uncovered a novel
      role of OX40 in sustaining Treg competitive fitness in vivo, during repopulation
      of lymphopenic hosts and reconstitution of BM chimeras. Defective expansion of
      OX40-null Treg diminished their ability to suppress inflammation in a model of
      lymphopenia-driven colitis. OX40-mediated promotion of Treg fitness spanned
      beyond lymphopenic environments, as endogenous Treg in OX40-null mice showed
      decreased accumulation during thymic development, enhanced susceptibility to
      antibody-mediated depletion and defective turnover following thymectomy. In
      vitro, OX40-deficient Treg were found to be intrinsically hyporesponsive to IL-2,
      in terms of Stat5 phosphorylation and proliferation, according to elevated SOCS1
      content and reduced miR155 expression. Therefore, OX40 is a key factor in shaping
      Treg sensitivity to IL-2 and promoting their proliferation and survival, toward
      accurate immune regulation.

PMID- 20806293
TI  - Spatial expectations of young human infants, following passive movement.
AB  - Three experiments are described that investigate 4.5-month-old infants' spatial
      thinking during passive movement using a task that required no manual or visual
      search. In these experiments, infants habituated to a display located near one
      corner of a table. Before the test trial the infants were either moved to the
      opposite side of the table or they remained in the same position that they held
      during the habituation trials. Also, between the habituation trials and the test
      trial, the display was either surreptitiously moved to the diagonally opposite
      position on the table, or the display remained stationary. The results showed
      that infants generally dishabituated when the actual (allocentric/objective)
      location of the display was changed between habituation and test. However, in
      Experiment 3, in which infants had reduced experience moving around the testing
      chamber, infants dishabituated to a change in their egocentric spatial
      relationship to the display. The results of this experiment suggest that
      experience moving around the testing chamber was a prerequisite for such location
      constancy. Taken together, the findings presented here indicate that with enough
      experience, young infants become aware of key spatial relationships in their
      environment during passive movement.

PMID- 20806296
TI  - Mechanical properties of dense zeolitic imidazolate frameworks (ZIFs): a high
      pressure X-ray diffraction, nanoindentation and computational study of the zinc
      framework Zn(Im)2, and its lithium-boron analogue, LiB(Im)4.
AB  - The dense, anhydrous zeolitic imidazolate frameworks (ZIFs), Zn(Im)(2) (1) and
      LiB(Im)(4) (2), adopt the same zni topology and differ only in terms of the
      inorganic species present in their structures. Their mechanical properties
      (specifically the Young's and bulk moduli, along with the hardness) have been
      elucidated by using high pressure, synchrotron X-ray diffraction, density
      functional calculations and nanoindentation studies. Under hydrostatic pressure,
      framework 2 undergoes a phase transition at 1.69 GPa, which is somewhat higher
      than the transition previously reported in 1. The Young's modulus (E) and
      hardness (H) of 1 (E~8.5, H~1 GPa) is substantially higher than that of 2 (E~3,
      H~0.1 GPa), whilst its bulk modulus is relatively lower (~14 GPa cf. ~16.6 GPa).
      The heavier, zinc-containing material was also found to be significantly harder
      than its light analogue. The differential behaviour of the two materials is
      discussed in terms of the smaller pore volume of 2 and the greater flexibility of
      the LiN(4) tetrathedron compared with the ZnN(4) and BN(4) units.

PMID- 20806297
TI  - Dynamic calcium metal-organic framework acts as a selective organic solvent
      sponge.
AB  - Herein, we present a Ca-based metal-organic framework named AEPF-1, which is an
      active and selective catalyst in olefin hydrogenation reactions. AEPF-1 exhibits
      a phase transition upon desorption of guest molecules. This structural
      transformation takes place by a crystal to crystal transformation accompanied by
      the loss of single-crystal integrity. Powder diffraction methods and
      computational studies were applied to determine the structure of the guest-free
      phase. This work also presents data on the exceptional adsorption behavior of
      this material, which is shown to be capable of separating polar from nonpolar
      organic solvents, and is a good candidate for selective solvent adsorption under
      mild conditions.

PMID- 20806298
TI  - Stereodivergent addition of 4-silyloxy-1,2-allenes to aldehydes by hydroboration.
AB  - All-ene one! Three out of four stereoisomers of 2-vinyl-1,3-diols can be obtained
      from a single allene. A simple variation of the reaction conditions modifies the
      stereochemical outcome of the addition of an allene to an aldehyde via
      hydroboration. Stereocontrol is dependent upon the order in which the reagents
      are mixed (leading to E or Z boron species) and the type of aldehyde (aliphatic
      or aromatic) used.

PMID- 20806299
TI  - Supramolecular structures and photoelectronic properties of the inclusion complex
      of a cyclic free-base porphyrin dimer and C60.
AB  - A cyclic free-base porphyrin dimer H4-CPD(Py) (CPD = cyclic porphyrin dimer)
      linked by butadiyne moieties bearing 4-pyridyl groups self-assembles to form a
      novel porphyrin nanotube in the crystalline state. The cyclic molecules link
      together through nonclassical C-H???N hydrogen bonds and pi-pi interactions of
      the pyridyl groups along the crystallographic a axis. H4-CPD(Py) includes a C60
      molecule in its cavity in solution. In the crystal structure of the inclusion
      complex (C60?H4-CPD(Py)), the dimer "bites" a C60 molecule by tilting the
      porphyrin rings with respect to each other, and there are strong pi-pi
      interactions between the porphyrin rings and C60. The included C60 molecules form
      a zigzag chain along the crystallographic b axis through van der Waals contacts
      with each other. Femtosecond laser flash photolysis of C60?H4-CPD(Py) in the
      solid state with photoexcitation at 420 nm shows the formation of a completely
      charge-separated state {H4-CPD(Py).+ + C60.-}, which decays with a lifetime of
      470 ps to the ground state. The charge-carrier mobility of the single crystal of
      C60?H4-CPD(Py) was determined by flash photolysis time-resolved microwave
      conductivity (FP-TRMC) measurements. C60?H4-CPD(Py) has an anisotropic charge
      mobility (SigmaMU = 0.16 and 0.13 cm2 V(-1)  s(-1)) along the zigzag chain of C60
      (which runs at 45 degrees  and parallel to the crystallographic b axis). To
      construct a photoelectrochemical cell, C60?H4-CPD(Py) was deposited onto
      nanostructured SnO2 films on a transparent electrode. The solar cell exhibited
      photovoltaic activity with an incident photon to current conversion efficiency of
      17%.

PMID- 20806300
TI  - A square-planar ruthenium(II) complex with a low-spin configuration.

PMID- 20806301
TI  - Organic sol-gel synthesis: solution-processable microporous organic networks.

PMID- 20806302
TI  - Scanning imaging of magnetic nanoparticles for quantitative molecular imaging.

PMID- 20806303
TI  - A quantum-dot-based molecular ruler for multiplexed optical analysis.

PMID- 20806304
TI  - Catalytic hydrogenation of norbornadiene by a rhodium complex in a self-folding
      cavitand.

PMID- 20806305
TI  - Facile synthesis of copper(II) immobilized on magnetic mesoporous silica
      microspheres for selective enrichment of peptides for mass spectrometry analysis.

PMID- 20806306
TI  - Template-directed syntheses of rigid oligorotaxanes under thermodynamic control.

PMID- 20806308
TI  - Spontaneous protein crowding in liposomes: a new vista for the origin of cellular
      metabolism.

PMID- 20806307
TI  - Multifaceted modes of action for the glutarimide-containing polyketides revealed.

PMID- 20806309
TI  - Cationic polymers with inhibition ability of DNA condensation elevate gene
      expression.

PMID- 20806310
TI  - Melanin-containing films: growth from dopamine solutions versus layer-by-layer
      deposition.
AB  - Films formed by oxidation of dopamine are of interest for functionalisation of
      solid-liquid interfaces owing to their versatility. However, the ability to
      modulate the properties of such films, for example, permeability to ionic species
      and the absorption coefficient, is urgently needed. Indeed, melanin films
      produced by oxidation of dopamine absorb strongly over the whole UV/Vis part of
      the electromagnetic spectrum and are impermeable to anions even for a film
      thickness as low as a few nanometers. Herein we combine oxidation of dopamine to
      produce a solution containing dopamine-melanin particles and their alternating
      deposition with poly(diallyldimethylammonium chloride) to produce films which
      have nearly the same morphology as pure dopamine-melanin films but are less
      compact, more transparent and more permeable to ferrocyanide anions.

PMID- 20806311
TI  - Kinetics and mechanisms for the reactions of ozone with unsaturated oxygenated
      compounds.
AB  - Rate coefficients for the reaction of ozone with a series of unsaturated
      oxygenated compounds are determined in air at atmospheric pressure and (298+/-3)
      K. Rate data are obtained using both relative and absolute rate techniques, and
      the measured rate coefficients are found to be in good agreement. The results
      show that the reactivity of the compounds with respect to addition of ozone to
      the double bond is a function of the nature of the oxygenated substituent.
      Product distribution studies on the reactions provide information on the
      decomposition pathways for the primary ozonides, and on the effect of the
      oxygenated group on the relative importance of the degradation pathways. The
      results are discussed in terms of their importance in the atmospheric oxidation
      of unsaturated oxygenated compounds.

PMID- 20806312
TI  - Synthesis and evaluation of bombesin analogues conjugated to two different
      triazolyl-derived chelators for (99m)Tc labeling.
AB  - Overexpression of the gastrin-releasing peptide receptor (GRPR) in a variety of
      human carcinomas has provided a means of diagnosis and treatment. Previously we
      reported a metabolically stable (N(alpha)His)Ac-betaAla-betaAla
      [Cha(13),Nle(14)]BBS(7-14) analogue with high affinity for the GRPR. We have also
      shown that the biodistribution pattern of this fairly lipophilic, radiolabeled
      peptide can be enhanced by glycation, which is easily carried out by Cu(I)
      catalyzed cycloaddition. Herein, we further elaborate this "click approach" in
      the synthesis of a new series of triazole-based chelating systems as alternatives
      to the (N(alpha)His)Ac chelator for labeling with the (99m)Tc(CO)(3) core. The
      bombesin analogues, containing these new chelating systems, were evaluated with
      regard to their synthesis and in vitro and in vivo properties, and were compared
      with their (N(alpha)His)Ac counterparts. The influence of the chelator on
      biodistribution properties was less than that of glycation, which clearly
      improved the tumor-to-background ratios.

PMID- 20806313
TI  - Critical factors in the seed-assisted synthesis of zeolite beta and "green beta"
      from OSDA-free Na+-aluminosilicate gels.
AB  - Organic structure-directing agent (OSDA)-free synthesis of zeolite beta is a
      subject of both scientific and industrial interest. Herein, we report a
      comprehensive investigation into the effects of various parameters on the seed
      assisted crystallization of zeolite beta in the absence of OSDA. The
      crystallization behavior of "OSDA-free beta" is strongly governed by the chemical
      composition of the starting Na(+)-aluminosilicate gel as well as by the Si/Al
      ratios of the calcined beta seed crystals, which are prepared using
      tetraethylammonium hydroxide (TEAOH). Furthermore, OSDA-free beta seed crystals
      can be used to form zeolite beta, termed "green beta". XRD, scanning electron
      microscopy, inductively coupled plasma atomic emission spectroscopy, and 27Al
      magic angle spinning NMR analyses showed that the OSDA-free beta and green beta
      were of high purity and crystallinity. The nitrogen adsorption-desorption of OSDA
      free beta and green beta revealed higher surface areas and larger volumes in the
      micropore region than those of the beta seeds synthesized with OSDA after
      calcination. These results provide a robust and reliable process for the
      environmentally friendly production of high-quality zeolite beta in a completely
      OSDA-free Na(+)-aluminosilicate system.

PMID- 20806314
TI  - In vivo fluorescence imaging of tumors using molecular aptamers generated by cell
      SELEX.
AB  - Poor sensitivity and low specificity of current molecular imaging probes limit
      their application in clinical settings. To address these challenges, we used a
      process known as cell-SELEX to develop unique molecular probes termed aptamers
      with the high binding affinity, sensitivity, and specificity needed for in vivo
      molecular imaging inside living animals. Importantly, aptamers can be selected by
      cell-SELEX to recognize target cells, or even surface membrane proteins, without
      requiring prior molecular signature information. As a result, we are able to
      present the first report of aptamers molecularly engineered with signaling
      molecules and optimized for the fluorescence imaging of specific tumor cells
      inside a mouse. Using a Cy5-labeled aptamer TD05 (Cy5-TD05) as the probe, the in
      vivo efficacy of aptamer-based molecular imaging in Ramos (B-cell lymphoma)
      xenograft nude mice was tested. After intravenous injection of Cy5-TD05 into mice
      bearing grafted tumors, noninvasive, whole-body fluorescence imaging then allowed
      the spatial and temporal distribution to be directly monitored. Our results
      demonstrate that the aptamers could effectively recognize tumors with high
      sensitivity and specificity, thus establishing the efficacy of these fluorescent
      aptamers for diagnostic applications and in vivo studies requiring real-time
      molecular imaging.

PMID- 20806315
TI  - Catalyst-controlled ring-opening cycloisomerization reactions of cyclopropenyl
      carboxylates for highly regioselective synthesis of different 2-alkoxyfurans.
AB  - Differently substituted 2-alkoxyfurans (2,3,4- or 2,3,5-trisubstituted furans)
      were highly regioselectively synthesized by means of the ring-opening
      cycloisomerization of the same cyclopropenyl carboxylates with good yields in
      different solvents and excellent regioselectivity by using [Cu(acac)(2)]
      (acac=acetylacetonate) or [RuCl(2)(PPh(3))(3)] as the catalyst, respectively. The
      structures of these two different types of furans were established by X-ray
      diffraction studies. A rationale has been proposed.

PMID- 20806316
TI  - Metal-free porphyrin-sensitized mesoporous titania films for visible-light indoor
      air oxidation.
AB  - Transparent cubic mesoporous TiO2 films coated on soda-lime glass have been
      developed. A metal free meso-tetrakis(4-sulfonatophenyl) porphyrin (TPPS) has
      been adsorbed on these TiO2 films from aqueous solutions. The results indicated
      that the obtained mesoporous TiO2 and 3D TPPS/TiO2 films are optically
      transparent and crack free (thickness ca. 200+/-20 nm). The introduction of the
      TPPS molecules has only a very small influence on the pore system and some
      limited pore blocking seems to occur. Transmission electron microscopy (TEM)
      images revealed that the adsorption of TPPS does not disrupt the meso order of
      TPPS/TiO2. The particle size of these TiO2 nanocrystals has been measured to be
      approximately 5-8 nm. TPPS/TiO2 photocatalysts, exhibiting regularly ordered
      mesopores, large surface area (ca. 102.5 cm(2) cm(-2)), and specific pore volume
      of about 0.1 mm(3) cm(-2), show improved light-harvesting efficiency as compared
      with other transparent TiO2 films. Employing the 3D TPPS/TiO2 photocatalyst, a
      quantum efficiency of 0.059 % has been obtained for the photodegradation of
      CH3CHO in the gas phase under visible-light illumination. Recycling tests
      demonstrated that the newly synthesized photocatalyst was quite stable during
      this gas-solid heterogeneous photocatalytic process because no significant
      decrease in photocatalytic activity was observed even after being used
      repetitively up to five times. Therefore, the newly synthesized transparent 3D
      TPPS/TiO2 photocatalysts can potentially be applied for low-cost air purification
      and self-cleaning applications.

PMID- 20806317
TI  - Ionic-liquid-stabilized rhodium nanoparticles for citral cyclodehydration.

PMID- 20806319
TI  - Titanium particles activate toll-like receptor 4 independently of lipid rafts in
      RAW264.7 murine macrophages.
AB  - Adherent pathogen-associated molecular patterns (PAMPs) act through toll-like
      receptor 2 (TLR2) and TLR4 to increase the biological activity of orthopedic wear
      particles in cell culture and animal models of implant loosening. This study
      tested whether this is dependent on TLR association with lipid rafts as reported
      for the response to soluble TLR ligands. For this purpose, RAW264.7 murine
      macrophages were activated by exposure to titanium particles with adherent PAMPs,
      soluble lipopolysaccharide (LPS), soluble lipotecichoic acid (LTA), or heat
      killed bacteria that had been extensively washed to remove soluble PAMPs. Lipid
      rafts were isolated by two independent methods and the location of TLR4 and TLR2
      was analyzed by Western blotting. The cognate TLRs associated with lipid rafts
      when the macrophages were activated with soluble LPS and LTA but not after
      stimulation with either titanium particles with adherent PAMPs or heat-killed
      bacteria. The lipid raft disruptor, methyl-beta-cyclodextrin, dose-dependently
      inhibited TNF-alpha release in response to LPS but had no affect on TNF-alpha
      release in response to titanium particles with adherent PAMPs. We conclude,
      therefore, that titanium particles with adherent PAMPs and heat-killed bacteria
      activate TLR2 and TLR4 in macrophages without inducing either TLR to associate
      with lipid rafts. These results have important implications for the mechanisms of
      orthopedic implant loosening as well the mechanisms for TLR activation in other
      inflammatory situations.

PMID- 20806320
TI  - Role of mitogen-activated protein kinase in osteoblast differentiation.
AB  - Local control of osteoblast differentiation and bone formation is not well
      understood. We have previously seen biphasic effects on cell differentiation in
      response to the short- and long-term exposure to IL-1beta in rat calvarial
      osteoblasts. To characterize the signaling pathway mechanisms regulating IL-1beta
      biphasic effects, we examined the contribution of mitogen-activated protein
      kinase (MAPK) family. Cells were pretreated with specific inhibitors to
      extracellular signal-regulated kinase (ERK, PD98059), p38 (SB203580), and c-JUN N
      terminal kinase (JNK, SP600125), then co-cultured with IL-1beta for 2, 4, and 6
      days. Cell differentiation was determined by measuring bone nodules after 10 days
      of culture. These inhibitors did not alter biphasic effects of IL-1beta on cell
      differentiation. However, PD98059 and U2016, another inhibitor of ERK activation
      robustly increased osteoblast differentiation compared to vehicle-treated control
      in a time- and dose-dependent manner. PD98059 appears to stimulate alkaline
      phosphatase (ALP) activity to promote cell differentiation, where IL-1beta
      appears to suppress it. Interestingly, continuous ERK inhibition with PD98059,
      after 2 and 4 days of IL-1beta treatment, enhanced the IL-1beta anabolic effect
      by increasing bone nodules formed. These observations provide a potential
      mechanism involving ERK pathway in osteoblasts differentiation and suggest that
      MAPK family may not directly regulate IL-1beta biphasic effects.

PMID- 20806322
TI  - Coherence regularization for SENSE reconstruction with a nonlocal operator
      (CORNOL).
AB  - The sensitivity encoding (SENSE) reconstruction reconstruction of parallel
      imaging can suffer from amplified noise at high reduction factors due to the ill
      conditioned system matrix. Regularization alleviates this problem by imposing
      priors on the reconstructed image. These priors typically introduce both
      intrastructure smoothness and interstructure smoothness. The former mainly
      reduces noise, while the latter can also decrease intensity changes between
      different structures and cause structure loss. In this study, coherence
      regularization was proposed to impose only intrastructure smoothness in order to
      enhance the preservation of the image structure. Its energy functional was formed
      by examining the connection between regularization and the diffusion equation of
      adaptive image filtering. The coherence regularization extracts image structure
      information directly from the noisy data by adapting diffusion equation-related
      image-filtering methods. In this study, a nonlocal operator derived from the
      nonlocal mean filter was used for structure detection. Based on this structure
      information, only intrastructure intensity changes are penalized while the
      interstructure intensity changes are preserved. Both phantom simulation and in
      vivo experiments demonstrate that the coherence regularization would be able to
      effectively suppress noise in SENSE reconstruction at high reduction factors
      while suffering from much less image degradation, compared to Tikhonov and total
      variation methods.

PMID- 20806318
TI  - Essential genes for astroglial development and axon pathfinding during zebrafish
      embryogenesis.
AB  - The formation of the central nervous system depends on the coordinated
      development of neural and glial cell types that arise from a common precursor.
      Using an existing group of zebrafish mutants generated by viral insertion, we
      performed a "shelf-screen" to identify genes necessary for astroglial development
      and axon scaffold formation. We screened 274 of 315 viral insertion lines using
      antibodies that label axons (anti-Acetylated Tubulin) and astroglia (anti-Gfap)
      and identified 25 mutants with defects in gliogenesis, glial patterning,
      neurogenesis, and axon guidance. We also identified a novel class of mutants
      affecting radial glial cell numbers. Defects in astroglial patterning were always
      associated with axon defects, supporting an important role for axon-glial
      interactions during axon scaffold development. The genes disrupted in these viral
      lines have all been identified, providing a powerful new resource for the study
      of axon guidance, glio- and neurogenesis, and neuron-glial interactions during
      development of the vertebrate CNS.

PMID- 20806321
TI  - Sorafenib in patients with metastatic renal cell carcinoma refractory to either
      sunitinib or bevacizumab.
AB  - BACKGROUND: Bevacizumab and sunitinib are standard initial therapy in metastatic
      renal cell carcinoma (mRCC). Despite common use, the safety and activity of
      sorafenib in bevacizumab- or sunitinib-refractory mRCC have not been
      prospectively investigated. METHODS: Metastatic RCC patients with Response
      Evaluation Criteria in Solid Tumors (RECIST)-defined disease progression (PD)
      after treatment with either bevacizumab or sunitinib received twice daily 400 mg
      of sorafenib in a multicenter, prospective phase 2 study. Dose escalation was
      permitted in the absence of significant toxicity. The primary endpoint was tumor
      burden reduction rate, defined as the proportion of patients with >=5% reduction
      in the sum of RECIST-defined target lesions without other PD. Secondary endpoints
      included progression-free survival (PFS), duration of response, overall survival,
      and safety. A 2-stage accrual design was used to test the alternative hypothesis
      that the tumor burden reduction rate was >20% versus <5%. RESULTS: Forty-eight
      patients were enrolled. The tumor burden reduction rate was 30% (95% confidence
      interval [CI], 17%-45%). One unconfirmed objective partial response was observed.
      The median PFS was 4.4 months (95% CI, 3.6-5.9). There was no association of PFS
      and tumor shrinkage with response to prior therapy. Most treatment-related
      adverse events were of mild-to-moderate intensity, and included fatigue,
      hypertension, diarrhea, and palmoplantar erythrodysesthesia (PPE). Patients
      previously treated with bevacizumab tended to develop more PPE (P=.03) and
      mucositis (P=.06), whereas sunitinib-treated patients tended to develop more skin
      rash (P=.06). CONCLUSIONS: Administration of sorafenib is safe and feasible in
      patients with mRCC refractory to either bevacizumab or sunitinib. Modest clinical
      activity was observed supporting current practice patterns of sequential vascular
      endothelial growth factor-targeted therapy in mRCC.

PMID- 20806323
TI  - Developmental motor function plays a key role in visual search.
AB  - Adults often miss a disturbingly high percentage of rare targets in visual
      arrays. The mechanisms underlying this effect remain hotly debated. This study
      examines the effects of developing motor control on the speed and accuracy of
      visual search. Children detected targets that appeared rarely or frequently.
      Participants reported a target's presence or absence by either pressing a key or
      marking on recording sheets. The results replicated past reports of increased
      errors with reduced target prevalence in adults. A potential developmental trend
      in performance is linked to a measure of motor function. When the pressure to
      respond quickly was removed, search accuracy greatly improved for rare targets. A
      developmental account for the perceptual-motor mechanisms of prevalence effect is
      discussed.

PMID- 20806324
TI  - Brain responses to surprising sounds are related to temperament and parent-child
      dyadic synchrony in young children.
AB  - This study investigated the relationship between temperament characteristics,
      parent-child dyadic synchrony and auditory event-related potentials (ERP) in 15
      two-year-old children. Temperament was assessed with the Early Childhood Behavior
      Questionnaire, and parent-child dyadic synchrony was analyzed from video-taped
      play situations. Involuntary switching of attention toward surprising sounds was
      measured with auditory ERPs by quantifying the P3a response for repeated and
      nonrepeated novel, naturally varying sounds, presented in a continuous repetitive
      sound sequence. Lower negative emotionality, higher effortful control and higher
      dyadic synchrony were associated with larger P3a responses to repeated novel
      sounds. The results demonstrate that temperament is related to P3a responses in
      early childhood, and that parent-child synchrony associates with both temperament
      and P3a responses in a theoretically meaningful way.

PMID- 20806325
TI  - Spontaneous kicking in full-term and preterm infants with and without white
      matter disorder.
AB  - Early damage to white matter of the brain may have developmental consequences for
      prematurely born infants including the coordination of leg movements. Our
      perspective is that white matter damage initiates an ontogenetic course that may
      lead to movement dysfunction leading to disability. In this study, spontaneous
      kicking in the human infant is a "window" for evaluating the potential
      consequences of perinatal brain damage for sensori-motor coordination. We compare
      the intra-limb coordination patterns of 5-month-old premature infants with white
      matter damage (PTWMD) to a group of prematurely born infants without WMD (PT) and
      a group of full-term (FT) infants. The PT group demonstrates advanced kicking
      patterns in comparison to both the PTWMD and FT groups. The PTWMD group has less
      mature patterns than the FT group on some, but not all measures. The movement
      challenge for PTWMD infants may be in the transition from spontaneous kicking to
      movements with the legs that require decoupling of intralimb joints.

PMID- 20806326
TI  - Vaginocervical stimulation of Ewes induces the rapid formation of a new bond with
      an alien young without interfering with a previous bond.
AB  - Ewes form a selective olfactory memory for their lambs after 2 hr of mother-young
      interaction following parturition. Mothers will subsequently reject any strange
      lamb at suckling. The present study investigated whether artificial
      vaginocervical stimulation (VCS) allows the formation of a selective bond with an
      unfamiliar lamb and whether it interferes with the maintenance of the bond formed
      with the familiar lamb. At 2 hr postpartum, mothers were separated from their
      familiar lamb after having formed a selective bond with it and were given 10 min
      of mechanical VCS. In the "VCS + lamb" group (n = 24) an unfamiliar lamb was left
      with the ewe for 2 hr whereas in the "VCS no lamb" group (n = 26) the mother was
      left alone for the same period of time. Ewes of the "no VCS" group (n = 14) did
      not receive any VCS. In the majority of animals of the "VCS + lamb" group (23/24)
      VCS induced a complete acceptance of the unfamiliar lamb without any disruption
      of the bond previously formed with the familiar lamb. VCS or 2 hr of separation
      did not disrupt the maintenance of the selective bond initially formed with the
      familiar lamb since all the ewes of the "VCS no lamb" and "no VCS" groups
      accepted it at suckling.

PMID- 20806328
TI  - Ordinary variations in human maternal caregiving in infancy and biobehavioral
      development in early childhood: A follow-up study.
AB  - Rodent models of early caregiving find that pups reared by dams providing low
      levels of early stimulation subsequently display heightened stress reactivity and
      social aggression. We examined these effects in humans by investigating the
      effects of early caregiving on markers of biobehavioral development at ages 2 and
      3 years. This study extended the findings reported by Hane and Fox (Hane and Fox
      [2006] Psychol. Sci. 17: 550-556) in which 185 mothers and infants were observed
      and scored for variations in maternal caregiving behavior (MCB) at age 9 months.
      Relative to young children who received high-quality MCB in infancy, those who
      received low-quality MCB showed significantly higher socially inhibited behavior
      with adults, right frontal electroencephalographam (EEG) asymmetry, aggressive
      play, and maternal reported internalizing behavior problems and anger proneness.
      These effects were independent of early temperamental reactivity. Results
      parallel rodent models and demonstrate that ordinary variations in MCB influence
      stress reactivity and social behavior in young children.

PMID- 20806329
TI  - Developmental instability of ano-genital distance index: Implications for
      assessment of prenatal masculinization.
AB  - Prenatal androgens are generally assumed to permanently affect the morphology of
      external genitalia. In laboratory rodents, the ano-genital distance index (AGDI)
      has become widely used as a marker of natural prenatal masculinization. A greater
      value should indicate a greater masculinization. The aim of this study was to
      assess the developmental stability of the AGDI in female mice during pre- (Days 1
      21) and postweaning (Days 21-61) periods. Presuming that the AGDI reflects a
      permanent effect of prenatal masculinization, we hypothesized that the AGDI will
      be a developmentally stable morphometric measurement (interindividual differences
      in the AGDI measurement should persist over time). In contrast to our prediction,
      the AGDI showed poor repeatability both during pre- (.15) and postweaning (.22)
      periods, indicating developmental instability. (A value of 1 indicates perfect
      repeatability and a value of 0 indicates no repeatability.) The AGDI thus does
      not seem to be a reliable marker of prenatal female masculinization.

PMID- 20806327
TI  - A comparison between taste avoidance and conditioned disgust reactions induced by
      ethanol and lithium chloride in preweanling rats.
AB  - Adult rats display taste avoidance and disgust reactions when stimulated with
      gustatory stimuli previously paired with aversive agents such as lithium chloride
      (LiCl). By the second postnatal week of life, preweanling rats also display
      specific behaviors in response to a tastant conditioned stimulus (CS) that
      predicts LiCl-induced malaise. The present study compared conditioned disgust
      reactions induced by LiCl or ethanol (EtOH) in preweanling rats. In Experiment 1
      we determined doses of ethanol and LiCl that exert similar levels of conditioned
      taste avoidance. After having equated drug dosage in terms of conditioned taste
      avoidance, 13-day-old rats were given a single pairing of a novel taste
      (saccharin) and either LiCl or ethanol (2.5 g/kg; Experiment 2). Saccharin intake
      and emission of disgust reactions were assessed 24 and 48 hr after training. Pups
      given paired presentations of saccharin and the aversive agents (ethanol or LiCl)
      consumed less saccharin during the first testing day than controls. These pups
      also showed more aversive behavioral reactions to the gustatory CS than controls.
      Specifically, increased amounts of grooming, general activity, head shaking, and
      wall climbing as well as reduced mouthing were observed in response to the CS.
      Conditioned aversive reactions but not taste avoidance were still evident on the
      second testing day. In conclusion, a taste CS paired with postabsorptive effects
      of EtOH and LiCl elicited a similar pattern of conditioned rejection reactions in
      preweanling rats. These results suggest that similar mechanisms may be underlying
      CTAs induced by LiCl and a relatively high EtOH dose.

PMID- 20806330
TI  - A preliminary study of cortisol reactivity and behavior problems in young
      children born premature.
AB  - The purpose of the present study was to examine the relation between cortisol
      reactivity and comorbid internalizing and externalizing behavior problems among
      children born premature. Children between the ages of 18 and 60 months who were
      born <37 weeks gestation and presented with clinically significant externalizing
      behavior problems were included. Children were categorized based on those who
      mounted a cortisol response to a stressor and those who did not mount a cortisol
      response. Children demonstrating the cortisol response were reported to have more
      problems with attention, emotional reactivity, anxiety, and depression based on
      maternal report and displayed higher rates of negative verbalizations during a
      mother-child interaction than children without a cortisol response. These results
      extend the findings of the relation between cortisol reactivity and comorbid
      internalizing and externalizing behavior problems to a sample of children born
      premature.

PMID- 20806332
TI  - Ontogeny of spatial working memory in the subterranean rodent ctenomys talarum.
AB  - While several works analyzed the spatial learning and memory capacities in adults
      of subterranean rodents, no study was done examining the development of these
      cognitive processes in pups of any of those species. Therefore, the development
      of spatial working memory in the South American subterranean rodent Ctenomys
      talarum was investigated by analyzing the pups' spatial performance in a delayed
      alternation task. When a short delay of 1 min was interposed between runs in the
      Y-maze, 20-day-old pups made more errors than 40- and 60-day-old pups. When
      longer intervals (10 min) were elapsed between runs, younger pups made
      approximately twice as many errors as the ones committed by 60-day-old pups,
      showing the age-dependent development of spatial working memory in this species
      of subterranean rodent. Increased space use by C. talarum pups, caused first by
      the appearance of independent exploratory behavior and later by the need of
      leaving maternal territory and construct a new burrow system, showed some
      correspondence with the improvements in the pups' spatial working memory
      performance, suggesting for the importance of this cognitive capacity in
      developing pups for which spatial learning and memory constitute essential
      abilities for survival and fitness.

PMID- 20806331
TI  - Role of medial prefrontal NMDA receptors in spatial delayed alternation in 19-,
      26-, and 33-day-old rats.
AB  - Long-Evans rats were trained on spatial delayed alteration (SDA) in a T-maze
      following medial prefrontal cortical (mPFC) infusions of different doses of the
      noncompetitive NMDA-receptor antagonist, MK-801 (.125 microl; .25 microl; or .25
      microlsaline, bilaterally), on postnatal day (PND) 19, 26, or 33. Pups trained on
      PND 19 showed almost no learning of SDA, regardless of drug condition (including
      saline). On PND 26, both doses of MK-801 significantly and equivalently prevented
      SDA learning, with performance during the final three training blocks remaining
      near chance levels, in contrast with 85% correct performance in the saline
      control group. On PND 33, substantial SDA learning was evident regardless of
      dose, although a modest impairment appeared in mid-training at both doses. These
      findings confirm previous reports of mPFC involvement in the early postnatal
      ontogeny of SDA and suggest a developmentally transient role of mPFC NMDA
      receptor function in this task.

PMID- 20806333
TI  - Children's and adults' salivary alpha-amylase responses to a laboratory stressor
      and to verbal recall of the stressor.
AB  - Salivary alpha-amylase (sAA), an enzyme produced by the salivary glands,
      increases in response to physical and psychosocial stressors in adults. Whether
      similar increases are evident among children, though, is less clear, and there is
      a lack of studies directly comparing children's and adults' sAA responses to an
      identical stressor. In this study, 24 children (9-12 years; 12 female) and 26
      adults (18-23 years; 16 female) were exposed to an identical psychosocial
      laboratory stressor and a recall interview regarding that stressor after a 2-week
      delay. Saliva was collected before and 1, 10, 20, and 30 min after the
      stressor/recall interview. Among adults, concentrations of sAA increased on both
      study days, but similar increases were not detected among children. Findings
      suggest developmental differences in sAA reactivity, and underscore the need to
      characterize the confluence of elements that will reliably elicit sAA responses
      to mild stress in youth.

PMID- 20806335
TI  - The ethnoprimatological approach in primatology.
AB  - Recent and long-term sympatries between humans and nonhuman primates (hereafter
      primates) are central to the behavioral ecology, conservation, and evolutionary
      trajectories of numerous primate species. Ethnoprimatology emphasizes that
      interconnections between humans and primates should be viewed as more than just
      disruptions of a "natural" state, and instead anthropogenic contexts must be
      considered as potential drivers for specific primate behavioral patterns. Rather
      than focusing solely on the behavior and ecology of the primate species at hand,
      as in traditional primatology, or on the symbolic meanings and uses of primates,
      as in socio-cultural anthropology, ethnoprimatology attempts to merge these
      perspectives into a more integrative approach. As human pressures on environments
      continue to increase and primate habitats become smaller and more fragmented, the
      need for a primatology that considers the impact of human attitudes and behavior
      on all aspects of primate lives and survival is imperative. In this special
      issue, we present both data-driven examples and more general discussions that
      describe how ethnoprimatological approaches can be both a contribution to the
      core theory and practice of primatology and a powerful tool in our goal of
      conservation action.

PMID- 20806334
TI  - Moderate vagal withdrawal in 3.5-year-old children is associated with optimal
      performance on executive function tasks.
AB  - Vagal tone (measured via respiratory sinus arrhythmia, RSA) and vagal withdrawal
      (measured by decreases in RSA) have been identified as physiological measures of
      self-regulation, but little is known how they may relate to the regulation of
      cognitive activity as measured through executive function (EF) tasks. We expected
      that baseline measures of vagal tone, thought to be an indicator of attention,
      would correlate with EF performance. We also predicted that vagal withdrawal
      would allow for the reorientation of attention that is needed to succeed on EF
      tasks, but too much withdrawal would be detrimental. RSA measured at baseline was
      indeed related to EF performance in 220 3.5-year-old children, and those who
      exhibited a moderate decrease in RSA during the EF tasks outperformed children
      whose RSA decreased by too little or too much. These findings implicate vagal
      tone withdrawal as a psychophysiological measure of higher cognitive processes,
      most likely substantiated through increases in the levels of focused attention.

PMID- 20806336
TI  - Exploring cultural drivers for wildlife trade via an ethnoprimatological
      approach: a case study of slender and slow lorises (Loris and Nycticebus) in
      South and Southeast Asia.
AB  - Illegal and unsustainable trade in wildlife is a major conservation challenge.
      For Asian primates, economic and cultural traditions, and increased forest access
      mean that trade may have become detrimental for certain species. Slow and slender
      lorises (Nycticebus and Loris) are primates particularly prevalent in trade,
      determined until now by focused counts of lorises in regional markets. Here, we
      use international trade statistics and a participant-observer approach to assess
      culturally specific drivers for trade in lorises in South and Southeast Asia, to
      provide a broader context to help mitigate this practice. Analysis of
      international records for the last 30 years revealed that live animal trade was
      more prevalent than trade in body parts (slow lorises, 86.4%; slender lorises,
      91.4%), with Laos, Cambodia, and Thailand the largest exporters. We then examine
      drivers of international and domestic trade based on long-term data from 1994
      2009 in Sri Lanka, Cambodia, and Indonesia. We show that slender lorises are
      important in Sri Lankan folklore, but their use as pets and for traditional
      medicine is rare. Trade in Bengal slow and pygmy lorises in Cambodia for use in
      traditional medicines, a practice with deeply historical roots, is widespread.
      Despite its own set of myths about the magical and curative properties of
      lorises, trade in Javan, Bornean, and greater slow lorises in Indonesia is
      largely for pets. Conservation practices in Asia are often generalized and linked
      with the region's major religions and economies. We show here that, in the case
      of wildlife trade, culturally specific patterns are evident among different
      ethnic groups, even within a country. Revealing such patterns is the foundation
      for developing conservation management plans for each species. We suggest some
      participatory methods for each country that may aid in this process.

PMID- 20806337
TI  - Behavioral responses of one western lowland gorilla (Gorilla gorilla gorilla)
      group at Bai Hokou, Central African Republic, to tourists, researchers and
      trackers.
AB  - Gorilla tourism, widely perceived as a lucrative industry, is propelled by strong
      market demand with programs in five countries and for three of four gorilla
      subspecies. Human presence may negatively affect wild gorillas, potentially
      lowering immunity and increasing the likelihood of acquiring human-borne disease.
      Yet, behavioral impacts of humans on wild gorilla behavior remain largely
      unexplored, particularly for western lowland gorillas. We evaluate the impact of
      tourist presence, human observer numbers (tourists, trackers, and researchers),
      and human observer distance on the behavior of one habituated gorilla group at
      Bai Hokou, Central African Republic. Behavioral data were collected for more than
      12 months from January 2007. Of silverback aggressive events, 39% (N=229) were
      human directed, but 65% were low-level soft barks. Adult females, and one in
      particular, were responsible for the highest number of aggressive events toward
      humans. Humans maintained closer proximity to the silverback when tourists were
      present, although tourist numbers had no significant impact on overall group
      activity budgets or rates of human-directed aggression. However, as research team
      size increased, group feeding rates decreased. Close observer-silverback distance
      correlated with a decrease in his feeding rates and an increase in human
      monitoring. He directed less aggression toward observers at distances >10 m,
      although observers spent 48.5% of time between 6 and 10 m of the silverback. We
      discuss gorilla personality as a factor in human-directed aggression. We explore
      whether the current 7 m distance limit governing gorilla tourism, based on
      disease transmission risks, is sufficient considering the potential behavioral
      stressor of close human presence. We recommend increasing minimum observation
      distance to >10 m where possible, decreasing observer group sizes, particularly
      after a visit consisting of maximum numbers and restricting tourist access to 1
      visit/day.

PMID- 20806338
TI  - Chimpanzee responses to researchers in a disturbed forest-farm mosaic at Bulindi,
      western Uganda.
AB  - We describe the behavior of a previously unstudied community of wild chimpanzees
      during opportunistic encounters with researchers in an unprotected forest-farm
      mosaic at Bulindi, Uganda. Data were collected during 115 encounters between May
      2006 and January 2008. Individual responses were recorded during the first minute
      of visual contact. The most common responses were "ignore" for arboreal
      chimpanzees and "monitor" for terrestrial individuals. Chimpanzees rarely
      responded with "flight". Adult males were seen disproportionately often relative
      to adult females, and accounted for 90% of individual responses recorded for
      terrestrial animals. Entire encounters were also categorized based on the
      predominant response of the chimpanzee party to researcher proximity. The most
      frequent encounter type was "ignore" (36%), followed by "monitor" (21%),
      "intimidation" (18%) and "stealthy retreat" (18%). "Intimidation" encounters
      occurred when chimpanzees were contacted in dense forest where visibility was
      low, provoking intense alarm and agitation. Adult males occasionally acted
      together to repel researchers through aggressive mobbing and pursuit. Chimpanzee
      behavior during encounters reflects the familiar yet frequently agonistic
      relationship between apes and local people at Bulindi. The chimpanzees are not
      hunted but experience high levels of harassment from villagers. Human-directed
      aggression by chimpanzees may represent a strategy to accommodate regular
      disruptions to foraging effort arising from competitive encounters with people
      both in and outside forest. Average encounter duration and proportion of
      encounters categorized as "ignore" increased over time, whereas "intimidation"
      encounters decreased, indicating some habituation occurred during the study.
      Ecotourism aimed at promoting tolerance of wildlife through local revenue
      generation is one possible strategy for conserving great apes on public or
      private land. However, the data imply that habituating chimpanzees for viewing
      based ecotourism in heavily human-dominated landscapes, such as Bulindi, is ill
      advised since a loss of fear of humans could lead to increased negative
      interactions with local people.

PMID- 20806339
TI  - Perceptions of nonhuman primates in human-wildlife conflict scenarios.
AB  - Nonhuman primates (referred to as primates in this study) are sometimes revered
      as gods, abhorred as evil spirits, killed for food because they damage crops, or
      butchered for sport. Primates' perceived similarity to humans places them in an
      anomalous position. While some human groups accept the idea that primates
      "straddle" the human-nonhuman boundary, for others this resemblance is a
      violation of the human-animal divide. In this study we use two case studies to
      explore how people's perceptions of primates are often influenced by these
      animals' apparent similarity to humans, creating expectations, founded within a
      "human morality" about how primates should interact with people. When animals
      transgress these social rules, they are measured against the same moral framework
      as humans. This has implications for how people view and respond to certain kinds
      of primate behaviors, their willingness to tolerate co-existence with primates
      and their likely support for primate conservation initiatives.

PMID- 20806341
TI  - Fibroblast activation protein expression in Crohn's disease strictures.

PMID- 20806340
TI  - Proteomic profiling of mucosal and submucosal colonic tissues yields protein
      signatures that differentiate the inflammatory colitides.
AB  - BACKGROUND: Differentiating ulcerative colitis (UC) from Crohn's colitis (CC) can
      be difficult and may lead to inaccurate diagnoses in up to 30% of inflammatory
      bowel disease (IBD) patients. Much of the diagnostic uncertainty arises from the
      overlap of clinical and histologic features. Matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI-MS) permits a histology-directed
      cellular protein analysis of tissues. As a pilot study, we evaluated the ability
      of histology-directed MALDI-MS to determine the proteomic patterns for potential
      differences between CC and UC specimens. METHODS: Mucosal and submucosal layers
      of CC and UC colon resection samples were analyzed after histologic assessment.
      To determine whether MALDI-MS would distinguish inflammation, the uninflamed (n =
      21) versus inflamed submucosa (n = 22) were compared in UC and the uninflamed (n
      = 17) versus inflamed submucosa (n = 20) in CC. To determine whether there were
      proteomic differences between the colitides, the uninflamed UC submucosa (n = 21)
      was compared versus the uninflamed CC submucosa (n = 17), the inflamed UC
      submucosa (n = 22) was compared versus the inflamed CC submucosa (n = 20), and
      inflamed UC mucosa versus inflamed CC mucosa. Pairwise statistics comparisons of
      the subsets were performed. RESULTS: Pairwise comparative analyses of the
      clinical groups allowed identifying subsets of features important for
      classification. Comparison of inflamed versus uninflamed CC submucosa showed two
      significant peaks: m/z 6445 (P = 0.0003) and 12692 (P = 0.003). In the case of
      inflamed versus uninflamed UC submucosa, several significant differentiating
      peaks were found, but classification was worse. Comparisons of the proteomic
      spectra of inflamed submucosa between UC and CC identified two discrete
      significant peaks: m/z 8773 (P = 0.006) and 9245 (P = 0.0009). Comparisons of the
      proteomic spectra of uninflamed submucosa between UC and CC identified three
      discrete significant peaks: m/z 2778 (P = 0.005), 9232 (P = 0.005), and 9519 (P =
      0.005). No significantly different features were found between UC and CC inflamed
      mucosa. CONCLUSIONS: MALDI-MS was able to distinguish CC and UC specimens while
      profiling the colonic submucosa. Further analyses and protein identification of
      the differential protein peaks may aid in accurately diagnosing IBD and
      developing appropriate personalized therapies.

PMID- 20806342
TI  - Ambient air pollution correlates with hospitalizations for inflammatory bowel
      disease: an ecologic analysis.
AB  - BACKGROUND: Known genetic loci account for less than 25% of the risk for
      inflammatory bowel disease (IBD), suggesting a potential role for environmental
      triggers. The association between ambient air pollution and IBD hospitalizations
      has not been previously studied. METHODS: Data from the Wisconsin Hospital
      Association (WHA) for the year 2002 was used to identify the number of IBD
      related hospitalizations for each of the 72 counties in Wisconsin. Average annual
      emissions density (2002) for each of the six criteria pollutants were obtained
      for each county from the Environmental Protection Agency. Pearson correlation and
      Poisson regression analysis were performed at the level of the county. RESULTS:
      There was a mean of 81.3 IBD hospitalizations/100,000 population per county
      (range 0-174). The total criteria pollutant emissions density correlated
      significantly with adult IBD hospitalizations (Pearson's correlation coefficient
      (rho) 0.28, P = 0.02). On Poisson regression, a 1-log increase in the density of
      total criteria pollutant emission was associated with a 40% increase in the rate
      of IBD hospitalizations (incidence rate ratio [IRR] 1.40, 95% confidence interval
      [CI] 1.31-1.50) This was similar for both ulcerative colitis (UC) (IRR 1.48, 95%
      CI 1.27-1.73) and Crohn's disease (CD) hospitalizations (IRR 1.39, 95% CI 1.26
      1.52). Analysis of each of the individual criteria pollutant emission densities
      revealed a significant association for all the component criteria pollutants.
      CONCLUSIONS: In this ecologic analysis, total air emissions of criteria
      pollutants appear to be associated with hospitalizations for IBD in adults. The
      ecologic design precludes drawing firm conclusions about association or causality
      and further research is needed.

PMID- 20806343
TI  - Systemic Toll-like receptor ligands modify B-cell responses in human inflammatory
      bowel disease.
AB  - BACKGROUND: Bacteria have a central, although poorly understood, role in
      inflammatory bowel disease (IBD). Host-bacteria interactions primarily take place
      in the gastrointestinal tract, but cells may also encounter translocated bacteria
      in the bloodstream. IBD is associated with activated, circulating Toll-like
      receptor (TLR)2 and TLR4-expressing B cells suggesting that blood-borne microbial
      TLR ligands modulate B cell responses. METHODS: Serum levels of
      lipopolysaccharide (LPS)/endotoxin and high mobility group box 1 (HMGB1), an
      endogenous TLR ligand, were quantified in Crohn's disease (CD) and ulcerative
      colitis (UC). Responses of purified B cells to LPS and HMGB1 were correlated with
      levels of systemic TLR ligands and clinical parameters of disease. RESULTS: While
      IBD patients have increased levels of blood LPS, the net effect of endotoxemia
      has unexpected characteristics illustrating that LPS has both pro- and
      antiinflammatory roles through TLR4+ B cells. Experimental treatment of B cells
      demonstrates that the antiinflammatory effect of LPS is due to its hypo-acylation
      of lipid A suggesting an increased prevalence of systemic, hypo-acylated LPS in
      CD. In contrast, high levels of LPS are associated with disease activity in UC.
      HMGB1 activates B cells through TLR2 and CD36. Serum levels of HMGB1 correlate
      with spontaneous IL-8 production by B cells suggesting that blood-borne TLR2
      ligands increase B-cell activation in vivo. CONCLUSIONS: Systemic TLR ligands
      modulate B cells towards either proinflammatory or antiinflammatory activity
      depending on the predominant ligand(s). Further, the circulating B cell may
      represent an important proxy for quantifying the LPS lipid A acylation burden in
      patients with IBD.

PMID- 20806344
TI  - Changes in blood flow velocity in the radial artery during 1-hour ultrasound
      monitoring with a 2-MHz transcranial probe--a pilot study.
AB  - PURPOSE: Multiple biologic effects of ultrasound on the human body have been
      described. Our aim was to monitor changes in blood flow velocities in the radial
      artery during continuous pulsed wave Doppler monitoring (DM). METHODS: Fifteen
      healthy volunteers (8 males; mean age 55 +/- 17 years) underwent two 1-hour
      sessions of left radial artery DM using a diagnostic transcranial 2-MHz pulsed
      wave transducer. Blood flow velocities were recorded twice at 2-minute intervals,
      for the measurement of peak systolic velocity, end-diastolic velocity, and mean
      flow velocity, and the calculation of pulsatility index, and resistance index.
      Insonation was either intermittent (by periods <10 seconds) or continuous during
      the first session, and conversely during the second session 2 weeks later.
      RESULTS: Blood flow velocities and indices fluctuated during both sessions. These
      changes were symmetrical during the intermittent DM session. In contrast, end
      diastolic velocity increased while pulsatility index and resistance index
      decreased significantly during the continuous DM session (p < 0.05 for all three
      parameters). The changes in peak systolic velocity and mean flow velocity did not
      differ between sessions. CONCLUSIONS: One-hour sonographic Doppler monitoring
      using a 2-MHz diagnostic transcranial PW Doppler probe may induce peripheral
      vasorelaxation in humans.

PMID- 20806345
TI  - Prenatal diagnosis of fetal hypothyroidism after maternal radioactive iodine
      exposure during pregnancy.
AB  - A 33-year-old woman with a history of surgically treated papillary thyroid
      carcinoma was inadvertently given radioactive iodine when she was 16 weeks
      pregnant. Sonographic examination revealed fetal thyroid hypoplasia, and
      cordocentesis confirmed fetal hypothyroidism at 22 weeks. The pregnancy was
      terminated at 24 weeks. We report the first case of fetal thyroid hypoplasia
      diagnosed by ultrasound and cordocentesis.

PMID- 20806346
TI  - Expression of the stem cell marker CD133 in recurrent glioblastoma and its value
      for prognosis.
AB  - BACKGROUND: Experimental data suggest that glioblastoma cells expressing the stem
      cell marker CD133 play a major role in radiochemoresistance and tumor
      aggressiveness. To date, however, there is no clinical evidence that the fraction
      of CD133-positive cells in glioblastoma that recurs after radiochemotherapy may
      be relevant for prognosis. METHODS: The authors used immunohistochemistry to
      assess CD133 expression in 37 paired glioblastoma samples, including 1 primary
      tumor sample and 1 recurrent tumor sample, after patients received adjuvant
      radiochemotherapy. To assess the actual composition of the CD133-positive
      glioblastoma cell population, fluorescence-associated cell sorting (FACS)
      analysis was used to sort CD133-positive/CD45-negative cells that were assayed
      for tumor-specific chromosomal aberrations using interphase fluorescence in situ
      hybridization. To rule out endothelial precursor cells, CD133-positive fractions
      also were assayed with anti-CD34 by FACS. RESULTS: In recurrent glioblastomas,
      the percentage of CD133-positive cells was increased by 4.6-fold compared with
      the percentage in primary glioblastomas, although, in some tumors, it increased
      up to 10-fold and 20-fold. Unexpectedly, the increase in CD133 expression was
      associated significantly with longer survival after tumor recurrence. An analysis
      of tumor-specific chromosomal aberrations and in vivo studies revealed that the
      CD133-positive cell compartment of recurrent glioblastoma was composed of both
      cancer stem cells and nontumor neural stem cells. The latter cells represented
      from 20% to 60% of the CD133-positive cell population, and their relative
      percentage favorably affected the survival of patients with recurrent
      glioblastoma. Endothelial CD133-positive/CD34-positive precursors did not
      contribute to the CD133-positive cell population. CONCLUSIONS: The authors
      hypothesized that, similar to the phenomenon described in glioblastoma models,
      neural stem/progenitor cells that are recruited by the tumor from surrounding
      brain may exert an antitumorigenic effect.

PMID- 20806347
TI  - Elevated expression of CXC chemokines in pediatric osteosarcoma patients.
AB  - BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children.
      Despite the advent of chemotherapy, the survival of osteosarcoma patients has not
      been significantly improved recently. Chemokines are a group of signaling
      molecules that have been implicated in tumorigenesis and metastasis. METHODS: The
      authors used an antibody microarray to identify chemokines that were elevated in
      the plasma samples of osteosarcoma patients. The results were validated using
      enzyme-linked immunosorbent assays on an independent set of samples. The tumor
      expressions of 3 chemokines were examined in 2 sets of osteosarcoma tissue
      arrays. The authors also evaluated the proliferative effect of the chemokines in
      4 osteosarcoma cell lines. RESULTS: The authors found that the plasma levels of
      CXCL4, CXCL6, and CXCL12 in the osteosarcoma patients were significantly higher
      than those in the controls, and the results were validated by an independent
      osteosarcoma cohort (P < .05). However, CXCL4 (100%) and CXCL6 (91%) were
      frequently expressed in osteosarcoma, whereas CXCL12 was only expressed in 4%.
      Survival analysis further showed that higher circulating levels of CXCL4 and
      CXCL6, but not CXCL12, were associated with a poorer outcome of osteosarcoma
      patients. Addition of exogenous chemokines significantly promoted the growth of
      different osteosarcoma cells (P < .05). CONCLUSIONS: The results demonstrate that
      CXCL4 and CXCL6 are frequently expressed in osteosarcoma, and that the plasma
      levels of these 2 chemokines are associated with patient outcomes. Further study
      of these circulating chemokines may provide a promising approach for
      prognostication of osteosarcoma. Targeting these chemokines or their receptors
      may also lead to a novel therapeutic invention.

PMID- 20806348
TI  - Sonographic assessment of fatty liver infiltration using the measurement of para-
      and perirenal fat thickness.
AB  - PURPOSE: Usefulness of abdominal ultrasonography for quantitative estimation of
      fatty liver by measurement of para- and perirenal sonographic fat thickness (UFT)
      was investigated. METHODS: Study subjects were 286 patients hospitalized for the
      treatment of diabetes. These subjects underwent blood chemistry studies,
      abdominal ultrasonography, and CT. On sonography, the thickness of combined para-
      and perirenal fat was measured between the kidney and the inner aspect of the
      abdominal musculature. Measurements on both sides were averaged as the UFT. Fatty
      liver infiltration was graded on a scale of grade 0 to 3: 0, none; 1, mild; 2,
      moderate; and 3, severe. With abdominal CT, the ratio of CT attenuation value of
      the liver to that of the spleen (L/S ratio) was measured. RESULTS: A positive
      correlation was found between UFT and FL grade or between UFT and L/S ratio (p <
      0.0001). Positive correlations were also found between UFT and glutamic pyruvic
      transaminase (p < 0.05), or cholinesterase (p < 0.0001). CONCLUSION: Measurement
      of UFT is a useful method for the quantification of fatty liver as well as for
      the quantification of visceral fat.

PMID- 20806349
TI  - Self-administered, subcutaneous alemtuzumab to treat residual disease in patients
      with chronic lymphocytic leukemia.
AB  - BACKGROUND: Alemtuzumab is highly effective at treating chronic lymphocytic
      leukemia (CLL) in bone marrow, which is the usual site of residual disease after
      fludarabine-based treatment. Eliminating residual disease potentially is
      associated with longer remission and overall survival. The authors of this report
      evaluated the ability of subcutaneous alemtuzumab to treat residual disease.
      METHODS: Patients in partial remission (PR), nodular PR (nPR), or complete
      remission (CR) who had disease in bone marrow established by 2-color flow
      cytometry analysis were enrolled and received alemtuzumab 30 mg subcutaneously 3
      times weekly for 4 weeks, and patients had the option to self-administer
      alemtuzumab. Responders were patients in PR who converted to an nPR or a CR,
      patients in nPR who converted to a CR, and patients in CR who had no evidence of
      disease on 2-color flow cytometry analysis after treatment. RESULTS: There were
      31 patients enrolled, of whom 29 were evaluable, and there were 23 responders (4
      of 4 patients who achieved a CR, 8 of 9 patients who achieved an nPR, and 11 of
      16 patients who achieved a PR. Nonresponders had significantly lower plasma
      alemtuzumab levels at the end of treatment. Furthermore, higher plasma
      alemtuzumab levels at the end of treatment were correlated with a longer response
      duration. Compared with the results from an historic group that received
      intravenous alemtuzumab for residual disease, there was a trend toward a higher
      response rate but a shorter response duration with subcutaneous alemtuzumab.
      CONCLUSIONS: The current results demonstrated that self-administered,
      subcutaneous alemtuzumab was safe and active for residual disease and that plasma
      alemtuzumab levels and real-time minimal residual disease evaluation are
      important endpoints to monitor in future alemtuzumab consolidation trials.

PMID- 20806351
TI  - Adverse effects of imatinib--dissecting heart from the rest.

PMID- 20806352
TI  - Impact of imaging landmark on the risk of MRI-related heating near implanted
      medical devices like cardiac pacemaker leads.
AB  - Implanted medical devices such as cardiac pacemakers pose a potential hazard in
      magnetic resonance imaging. Electromagnetic fields have been shown to cause
      severe radio frequency-induced tissue heating in some cases. Imaging exclusion
      zones have been proposed as an instrument to reduce patient risk. The purpose of
      this study was to further assess the impact of the imaging landmark on the risk
      for unintended implant heating by measuring the radio frequency-induced electric
      fields in a body phantom under several imaging conditions at 1.5T. The results
      show that global radio frequency-induced coupling is highest with the torso
      centered along the superior-inferior direction of the transmit coil. The induced
      E-fields inside the body shift when changing body positioning, reducing both
      global and local radio frequency coupling if body and/or conductive implant are
      moved out from the transmit coil center along the z-direction. Adequate selection
      of magnetic resonance imaging landmark can significantly reduce potential hazards
      in patients with implanted medical devices.

PMID- 20806353
TI  - Assessment of MR compatibility of a PET insert developed for simultaneous
      multiparametric PET/MR imaging on an animal system operating at 7 T.
AB  - The combination of positron emission tomography and MR in one system is currently
      emerging and opens up new domains in the functional examinations of living
      systems. This article reports on relevant influences of a positron emission
      tomography insert on MR imaging. The basic conditions of main magnetic field and
      RF field homogeneity were measured as well as image quality and signal-to-noise
      ratio when applying the usual MR sequence types including echo-planar techniques.
      Moreover, the influence of the positron emission tomography insert on the RF
      noise level and on RF interferences was measured by comparing results achieved
      with and without the positron emission tomography insert. The temporal stability
      of EPI imaging with and without the positron emission tomography insert was
      assessed. Small but significant decreases in the signal-to-noise ratio were
      revealed when the positron emission tomography insert was present, whereas B(0)
      and B(1) homogeneity as well as RF noise level were not adversely affected. A
      higher signal intensity drift was found for EPI imaging studies; however, this
      can be compensated by post processing. In summary, this study shows that positron
      emission tomography inserts can be designed for and used within an MR system
      practically, without substantially affecting the MR image quality.

PMID- 20806354
TI  - Robust 2D phase correction for echo planar imaging under a tight field-of-view.
AB  - Nyquist ghost artifacts are a serious issue in echo planar imaging. These
      artifacts primarily originate from phase difference between even and odd echo
      images and can be removed or reduced using phase correction methods. The commonly
      used 1D phase correction can only correct phase difference along readout axis. 2D
      correction is, therefore, necessary when phase difference presents along both
      readout and phase encoding axes. However, existing 2D methods have several
      unaddressed issues that affect their practicality. These issues include
      uncharacterized noise behavior, image artifact due to unoptimized phase
      estimation, Gibbs ringing artifact when directly applying to partial k(y) data,
      and most seriously a new image artifact under tight field-of-view (i.e., field-of
      view slightly smaller than object size). All these issues are addressed in this
      article. Specifically, theoretical analysis of noise amplification and effect of
      phase estimation error is provided, and tradeoff between noise and ghost is
      studied. A new 2D phase correction method with improved polynomial fitting, joint
      homodyne processing and phase correction, compatibility with tight field-of-view
      is then proposed. Various results show that the proposed method can robustly
      generate images free of Nyquist ghosts and other image artifacts even in oblique
      scans or when cross-term eddy current terms are significant.

PMID- 20806355
TI  - Fast human brain magnetic resonance responses associated with epileptiform
      spikes.
AB  - Neuronal currents produce local electromagnetic fields that can potentially
      modulate the phase of the magnetic resonance signal and thus provide a contrast
      mechanism tightly linked to neuronal activity. Previous work has demonstrated the
      feasibility of direct MRI of neuronal activity in phantoms and cell culture, but
      in vivo efforts have yielded inconclusive, conflicting results. The likelihood of
      detecting and validating such signals can be increased with (i) fast gradient
      echo echo-planar imaging, with acquisition rates sufficient to resolve neuronal
      activity, (ii) subjects with epilepsy, who frequently experience stereotypical
      electromagnetic discharges between seizures, expressed as brief, localized, high
      amplitude spikes (interictal discharges), and (iii) concurrent
      electroencephalography. This work demonstrates that both MR magnitude and phase
      show large-amplitude changes concurrent with electroencephalography spikes. We
      found a temporal derivative relationship between MR phase and scalp
      electroencephalography, suggesting that the MR phase changes may be tightly
      linked to local cerebral activity. We refer to this manner of MR acquisition,
      designed explicitly to track the electroencephalography, as encephalographic MRI
      (eMRI). Potential extension of this technique into a general purpose functional
      neuroimaging tool requires further study of the MR signal changes accompanying
      lower amplitude neuronal activity than those discussed here.

PMID- 20806356
TI  - Sox9-expressing precursors are the cellular origin of the cruciate ligament of
      the knee joint and the limb tendons.
AB  - Sox9 expression defines cell progenitors in a variety of tissues during mouse
      embryogenesis. To establish a genetic tool for cell-lineage tracing and gene
      function analysis, we generated mice in which the CreERT2 gene was targeted to
      the endogenous mouse Sox9 locus. In Sox9(CreERT2/+) ;R26R embryos, tamoxifen
      activated Cre recombinase exclusively in Sox9-expressing tissues. To determine
      the suitability of this mouse line for developmental stage-specific gene
      recombination, we investigated the cellular origins of the cruciate ligaments of
      the knee joint and the limb tendons, in which precursor cells have not been
      defined. The cells in these tissues were labeled after tamoxifen treatment before
      or at the stage of chondrogenic mesenchymal condensation, indicating that
      ligament and tendon cells originated from Sox9-expressing cells and that cell
      fate determination occurred at mesenchymal condensation. This mouse line is a
      valuable tool for the temporal genetic tracing of the progeny of, and inducible
      gene modification in Sox9-expressing cells.

PMID- 20806359
TI  - Oral chelation: should it be used with young children?
AB  - Deferasirox, the only oral iron chelator approved in the US and Canada, achieved
      a pediatric label indication down to 2 years of age. FDA-mandated post-marketing
      safety surveillance in children under age 6 is ongoing. We wish to raise a non
      safety-related concern with deferasirox chelation in very young children (2-5
      years old). Specifically, the circumstances required for reliable daily ingestion
      of deferasirox do not mesh well with the developmental characteristics common in
      young children, which may limit adherence and cause parental distress. We review
      developmental challenges associated with oral chelation in this age group and
      provide suggestions to improve adherence in this population.

PMID- 20806357
TI  - A Cre transgenic line for studying V2 neuronal lineages and functions in the
      spinal cord.
AB  - During spinal neurogenesis, the p2 progenitor domain generates at least two
      subclasses of interneurons named V2a and V2b, which are components of the
      locomotor central pattern generator. The winged-helix/forkhead transcription
      factor Foxn4 is expressed in a subset of p2 progenitors and required for
      specifying V2b interneurons. Here, we report the generation of a Foxn4-Cre BAC
      transgenic mouse line that drives Cre recombinase expression mimicking endogenous
      Foxn4 expression pattern in the developing spinal cord. We used this transgenic
      line to map neuronal lineages derived from Foxn4-expressing progenitors and found
      that they gave rise to all neurons of the V2a, V2b, and the newly identified V2c
      lineages. These data suggest that Foxn4 may be transiently expressed by all p2
      progenitors and that the Foxn4-Cre line may serve as a useful genetic tool not
      only for lineage analysis but also for functional studies of genes and neurons
      involved in locomotion.

PMID- 20806360
TI  - Treatment results for patients with localized, completely resected (Group I)
      alveolar rhabdomyosarcoma on Intergroup Rhabdomyosarcoma Study Group (IRSG)
      protocols III and IV, 1984-1997: a report from the Children's Oncology Group.
AB  - PURPOSE: To assess local control, event-free survival (EFS), and overall survival
      (OS) rates in 71 patients with localized, completely resected (Group I) alveolar
      rhabdomyosarcoma (ALV RMS) and their relation to radiation therapy (RT) on IRSG
      Protocols III and IV, 1984-1997. METHODS: Chart review and standard statistical
      procedures. PATIENTS AND TUMORS: Patients were 1-18 years at diagnosis (median, 6
      years). Primary tumor sites were extremity/trunk (N = 54), head/neck (N = 9),
      genitourinary tract (N = 7), and perineum (N = 1). Thirty patients received VA +/
      C with RT; 41 received VA +/- C alone. RT was assigned, not randomized. RESULTS:
      Fifty-four patients had Stage 1 (favorable site, any size) or Stage 2
      (unfavorable site, < or = 5 cm) tumors. Eight-year EFS was 90%, with 100% local
      control for 17 patients given RT. Eight-year EFS was 88%, with 92% local control
      for 37 patients without RT; P = 0.52 for EFS comparisons, 0.3 for local control
      comparisons. In 17 Stage 3 patients (unfavorable site, tumors >5 cm, N0), 8-year
      EFS was 84% with 100% local control in 13 patients given RT; 8-year EFS was only
      25% and local control 50% in 4 patients without RT. Local recurrence was the most
      common site of first failure in non-irradiated patients. CONCLUSION: Patients
      with Stage 1-2 ALV RMS had slightly but statistically insignificantly improved
      local control, EFS, and OS rates when local RT was given. The need for local RT
      in Stage 1-2 patients deserves evaluation in a randomized study. Local control,
      EFS, and OS rates were significantly improved in Stage 3 patients receiving local
      RT.

PMID- 20806361
TI  - Does Children's Oncology Group hospital membership improve survival for patients
      with neuroblastoma or Wilms tumor?
AB  - PURPOSE: To determine prognostic significance of hospital surgical volume and
      Children's Oncology Group (COG) membership on neuroblastoma (NBL) and Wilms tumor
      (WT) survival. METHODS: The Florida Cancer Data System was queried from 1981 to
      2004. RESULTS: Of 869 NBL patients, 463 were treated at COG/HVC, 246 at COG/LVC,
      and 160 at non-COG/LVC. COG hospitals treated a larger proportion of patients <1
      year of age (P = 0.002) and relatively more patients with adrenal and mediastinal
      tumors (P = 0.005). COG centers more frequently administered chemotherapy (72%
      vs. 51%, P < 0.001). Five- and 10-year survival rates were higher at COG/HVC
      (70.6%, 67.7%) and COG/LVC (75.8%, 72.6%) than non-COG/LVC (59.5%, 54.4%, P <
      0.05). Of 790 WT patients, 395 were treated at COG/HVC, 210 at COG/LVC, and 185
      at non-COG/LVC. COG hospitals treated younger patients and lower staged tumors (P
      < 0.05). COG centers more frequently administered chemotherapy (88% vs. 59%, P <
      0.001). Five- and 10-year survival rates were higher at COG/HVC (91.3%, 89.9%)
      and COG/LVC (96.7%, 94.7%) than non-COG/LVC (82.4%, 81.7%, P < 0.05).
      Multivariate analysis demonstrated WT patients treated at non-COG hospitals, but
      not NBL patients, had worse survival (HR 3.107, P = 0.01). CONCLUSION: Children
      treated at COG hospitals had higher overall use of chemotherapy. This translated
      into a significantly improved survival benefit for WT.

PMID- 20806362
TI  - Adjuvant radiotherapy in the treatment of pediatric myxopapillary ependymomas.
AB  - OBJECTIVES: Assess the role of radiotherapy (RT) in the management of primary and
      recurrent myxopapillary ependymoma (MPE). MATERIALS AND METHODS: We conducted a
      retrospective review of patients with MPE treated at the Montreal Children's
      Hospital/McGill University Health Centre between 1985 and 2008. RESULTS: Seven
      children under the age of 18 were diagnosed and treated for MPE. All patients
      were treated with surgery to the primary site. Three patients underwent subtotal
      resection (STR) and received adjuvant post-operative RT. Only one patient who had
      spinal drop metastases received post-operative RT to the lumbosacral region
      following complete resection of the primary tumor. After a median follow up of 78
      months (range 24-180 months), all patients were alive with controlled disease.
      The single patient treated with gross total resection (GTR) and adjuvant local
      radiation remained recurrence free. One of the three patients treated with STR
      and adjuvant RT had disease progression that was controlled with re-resection and
      further RT. Two of the three patients treated with surgery alone developed local
      and disseminated recurrent spinal disease that was controlled by salvage RT.
      CONCLUSION: Our data support the evolving literature which suggests that GTR
      alone provides suboptimal disease control in MPE. In our patients, RT resulted in
      control of residual, metastatic and/or recurrent disease. Routine adjuvant RT may
      improve outcomes in pediatric MPE.

PMID- 20806363
TI  - Non-metastatic osteosarcoma of the extremities in children aged 5 years or
      younger.
AB  - BACKGROUND: The occurrence of high-grade osteosarcoma is rare in children aged 5
      years or younger and only limited series or case reports have been described.
      METHODS: The records of patients aged 5 years or younger with non-metastatic high
      grade osteosarcoma of the extremities treated with surgery and adjuvant or neo
      adjuvant chemotherapy at Rizzoli Institute between 1972 and 1999 were
      retrospectively evaluated in relation to gender, primary tumor site, histological
      subtype, surgical treatment, chemotherapy-induced tumor necrosis, 5- and 10-year
      event-free survival (EFS), and rate of local recurrence. Data were compared to
      patients aged 6-40 years entered with the same diagnosis and over the same time
      interval. RESULTS: Data from 20 patients were collected. Comparing these data
      with those from 1,106 patients 6-40 years of age only two main differences
      resulted: the younger group showed a higher rate for fibroblastic subtype (P <
      0.01) and for amputation surgery (P < 0.01). Among the two groups, no statistical
      difference was observed for the 5-year EFS (60% vs. 53.8%; P = 0.6) and 10-year
      EFS (60% vs. 52.1%; P = 0.5). The rate of local recurrence was 5.0% and 5.4%.
      CONCLUSIONS: These findings suggest that in non-metastatic osteosarcoma of the
      extremities outcome and clinical characteristics are similar among children 5
      years of age or younger and older patients. However, in the younger group we have
      observed a significant higher rate of fibroblastic subtype as well as a
      significant higher rate of mutilating surgery. Pediatr Blood Cancer.

PMID- 20806364
TI  - Predicting the risk of severe bacterial infection in children with chemotherapy
      induced febrile neutropenia.
AB  - BACKGROUND: The prognosis of febrile neutropenia (FN) in childhood cancer has
      been considerably improved by the intensification of treatment, including
      systematic hospitalization and broad-spectrum antibiotics. As only few children
      present with a severe bacterial infection (SBI), clinical decision rules have
      been developed to distinguish those at risk for SBI. The aim of this study was to
      evaluate the reproducibility of six clinical decision rules proposed in the
      literature and to compare their performance. METHODS: This retrospective two
      center cohort study included all episodes of chemotherapy-induced FN in children
      admitted between January 2005 and December 2006. Each rule was applied to our
      patients. Their sensitivity (Se) and specificity (Sp) were calculated and
      compared with the authors' results, to assess reproducibility. The most
      predictive rule was defined in advance as that yielding 100% Se, the highest Sp,
      and the greatest simplicity for bedside application. RESULTS: Three hundred
      seventy-seven episodes of FN in 167 patients were collected; 64 episodes were
      associated with SBI, including 36 with bacteremia. Four of the six rules were
      reproducible, but none were able to be validated. The most predictive rule for
      bacteremia had 96% Se (95% confidence interval (CI): 79-99%) and 25% Sp (95% CI:
      19-33%), and the most predictive rule for SBI had 95% Se (95% CI: 87-98%), but no
      power of discrimination (Sp = 5%, 95% CI: 3-8%). CONCLUSION: This study
      emphasizes the difficulty in identifying standardized decision rules in the
      management of a condition with numerous clinical variables like FN.

PMID- 20806365
TI  - Initial testing (stage 1) of AZD6244 (ARRY-142886) by the Pediatric Preclinical
      Testing Program.
AB  - BACKGROUND: AZD6244 (ARRY-142886) is a potent small molecule inhibitor of MEK1/2
      that is in phase 2 clinical development. PROCEDURES: AZD6244 was tested against
      the Pediatric Preclinical Testing Program (PPTP) in vitro panel (1 nM-10 microM).
      In vivo AZD6244 was tested at a dose of 100 mg/kg administered orally twice daily
      5 days per week for 6 weeks. Subsequently, AZD6244 was evaluated against two
      juvenile pilocytic astrocytoma (JPA) xenografts using once and twice daily dosing
      schedules. Phosphorylation of ERK1/2 was used as a surrogate for in vivo
      inhibition of MEK1/2 was determined by immunoblotting. RESULTS: At the highest
      concentration used in vitro (10 microM) AZD6244 only inhibited growth by 50% in 5
      of the 23 cell lines. Against the in vivo tumor panels, AZD6244 induced
      significant differences in EFS distribution in 10 of 37 (27%) solid tumor models
      and 0 of 6 acute lymphoblastic leukemia (ALL) models. There were no objective
      responses. Pharmacodynamic studies indicated at this dose and schedule AZD6244
      completely inhibited ERK1/2 phosphorylation. AZD6244 was evaluated against two
      JPA xenografts, BT-35 (wild-type BRAF) and BT-40 (mutant [V600E] BRAF). BT-40
      xenografts were highly sensitive to AZD6244, whereas BT-35 xenografts progressed
      on AZD6244 treatment. CONCLUSIONS: At the dose and schedule of administration
      used, AZD6244 as a single agent had limited in vitro and in vivo activity against
      the PPTP tumor panels despite inhibition of MEK1/2 activity. However, AZD6244 was
      highly active against BT-40 JPA xenografts that harbor constitutively activated
      BRAF, causing complete regressions.

PMID- 20806366
TI  - T-cell acute lymphoblastic leukemia in association with Borjeson-Forssman-Lehmann
      syndrome due to a mutation in PHF6.
AB  - Borjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked mental retardation
      syndrome that is caused by germline mutations in PHF6. We describe a 9-year-old
      male with BFLS, who developed T-cell acute lymphoblastic leukemia (T-ALL). The
      PHF6 gene is located on the X chromosome and encodes a protein with two PHD-type
      zinc finger domains and four nuclear localization sequences. Previously,
      overexpression of Phf6 was observed in murine T-cell lymphomas. Our observation
      indicates that BFLS may represent a cancer predisposition syndrome and that
      mutations of PHF6 contribute to T-ALL.

PMID- 20806367
TI  - Spontaneous resolution of Epstein-Barr virus-associated hemophagocytic
      lymphohistiocytosis.
AB  - Secondary hemophagocytic lymphohistiocytosis (sHLH) is a reactive, proliferative
      disorder of the immune system resulting in lymphohistiocytic proliferation,
      hemophagocytosis, and cytokine dysregulation. The most common infectious trigger
      in sHLH is Epstein-Barr virus (EBV-HLH). Current treatment protocols for EBV-HLH
      have a cure rate of approximately 75%; however, there are significant toxicities
      associated with these therapies. We present two patients with EBV-HLH who
      experienced spontaneous resolution of their disease prior to the initiation of
      therapy, suggesting there may be a subgroup of patients with EBV-HLH who do well
      with conservative management and can avoid potentially toxic therapies.

PMID- 20806368
TI  - Dreaming about the homeland: nostalgia of immigrant children with cancer.

PMID- 20806369
TI  - Hypothyroidism after treatment of metastatic neuroblastoma.

PMID- 20806370
TI  - Pegfilgrastim plus AMD 3100 for stem-cell mobilization in children.

PMID- 20806372
TI  - Erythrocyte shape reversion from echinocytes to discocytes: kinetics via fast
      measurement NMR diffusion-diffraction.
AB  - Pulsed field-gradient spin-echo (PGSE) NMR spectroscopy via q-space plots can
      characterize erythrocyte shapes and their evolution. The present study employed
      PGSE NMR to investigate shape reversion from advanced echinocytic to normal
      discocytic shapes due to depletion and then readdition of Mg(2+). In q-space
      plots of the data, the diffusion-diffraction minima disappeared for Mg(2+)
      depleted erythrocytes and reappeared during the shape recovery process, but with
      lower definition than for control cells. Shape estimates from PGSE NMR spectra
      and light microscopy were in excellent agreement after application of a
      scaling/correction factor. (31)P NMR was used to probe the biochemical processes
      activated in erythrocytes after depletion or addition of Mg(2+); it showed the
      activation of the nonoxidative part of the pentose phosphate pathway.
      Experimental conditions were optimized to bypass this pathway without any
      influence on the q-space plots. The release of choline from phosphatidylcholine
      in the outer leaflet of the plasma membrane of the cells, observed using (1)H
      spin-echo NMR, showed a higher rate for shape-recovered than for control cells.
      This points to a change in phospholipid asymmetry in the plasma membrane. This
      variation in asymmetry affected the mean cell shape and hence influenced the
      average alignment of the erythrocytes with the static magnetic field and so
      affected the shapes of the q-space plots.

PMID- 20806373
TI  - 23Na and 2H magnetic resonance studies of osteoarthritic and osteoporotic
      articular cartilage.
AB  - In this study, the short component of the (23)Na T(2) (T(2f)) and the (23)Na and
      (2)H quadrupolar interactions (nu(Q)) were measured in bone-cartilage samples of
      osteoarthritic (OA) and osteoporotic (OP) patients. (23)Na nu(Q) was found to
      increase in osteoarthritic articular cartilage relative to controls. Similar
      results were found in bovine cartilage following proteoglycan (PG) depletion, a
      condition that prevails in osteoarthritis. (23)Na nu(Q) and 1/T(2f) for articular
      cartilage obtained from osteoporotic patients were significantly larger than for
      control and osteoarthritic cartilage. Decalcification of both human and bovine
      articular cartilage resulted in an increase of (23)Na nu(Q) and 1/T(2f), showing
      the same trend as the osteoporotic samples. Differences in the ratio of the
      intensity of the large (2)H splitting to that of the small one in the calcified
      zone were also observed. In osteoporosis, this ratio was twice as large as that
      obtained for both control and osteoarthritic samples. The (2)H and (23)Na results
      can be interpreted as due to sodium ions and water molecules filling the void
      created by the calcium depletion and to calcium ions being located in close
      association with the collagen fibers. To the best of our knowledge, this is the
      first study reporting differences of NMR parameters in cartilage of osteoporotic
      patients.

PMID- 20806374
TI  - Prospective motion correction for single-voxel 1H MR spectroscopy.
AB  - Head motion during (1)H MR spectroscopy acquisitions may compromise the quality
      and reliability of in vivo metabolite measurements. Therefore, a three-plane
      image-based motion-tracking module was integrated into a single-voxel (1)H MR
      spectroscopy (point-resolved spectroscopy) sequence. A series of three orthogonal
      spiral navigator images was acquired immediately prior to the MR spectroscopy
      water suppression module in order to estimate head motion. By applying the
      appropriate rotations and translations, the MR spectroscopy voxel position can be
      updated such that it remains stationary with respect to the brain. Frequency and
      phase corrections were applied during postprocessing to reduce line width and
      restore coherent averaging. Spectra acquired during intentional head motion in 11
      volunteers demonstrate reduced lipid contamination and increased spectral
      reproducibility when motion correction is applied.

PMID- 20806375
TI  - Characterization of 1H NMR signal in human cortical bone for magnetic resonance
      imaging.
AB  - Recent advancements in MRI have enabled clinical imaging of human cortical bone,
      providing a potentially powerful new means for assessing bone health with
      molecular-scale sensitivities unavailable to conventional X-ray-based
      diagnostics. In human cortical bone, MRI is sensitive to populations of protons
      ((1)H) partitioned among water and protein sources, which may be differentiated
      according to intrinsic NMR properties such as chemical shift and transverse and
      longitudinal relaxation rates. Herein, these NMR properties were assessed in
      human cortical bone donors from a broad age range, and four distinct (1)H
      populations were consistently identified and attributed to five microanatomical
      sources. These findings show that modern human cortical bone MRI contrast will be
      dominated by collagen-bound water, which can also be exploited to study human
      cortical bone collagen via magnetization transfer.

PMID- 20806376
TI  - Compartment-specific enhancement of white matter and nerve ex vivo using
      chromium.
AB  - Chromium--Cr(VI) in the form of potassium dichromate--has been shown to
      specifically enhance white matter signal. The proposed mechanism for this
      enhancement is reduction of diamagnetic Cr(VI) to paramagnetic chromium species
      by oxidizable myelin lipids. The purpose of the study herein was to better
      understand the microanatomical basis of this enhancement (i.e., the relative
      enhancement of myelin, intra-axonal, and extra-axonal water). Toward this end,
      integrated T(1)-T(2) measurements were performed in potassium dichromate loaded
      (hereafter referred to as chromated) rat brains, rat optic nerve samples, and
      frog sciatic nerve samples ex vivo. In control optic nerve and white matter, two
      T(1)-T(2) components were resolved, representing myelin and nonmyelin water
      (intra- and extra-axonal water). Following chromation, three T(1)-T(2) components
      were resolved in these same tissues. Results from similar measurements in sciatic
      nerve-all three components are resolvable in control and chromated samples-and
      quantitative histologic analysis suggest that this additional T(1)-T(2) component
      is due to a splitting of the nonmyelin water component into intra- and extra
      axonal water components. This compartment-specific enhancement may provide unique
      contrast for MR histology, as well as allow one to probe the compartmental basis
      of various contrast mechanisms in neural tissue.

PMID- 20806377
TI  - GRAPPA operator for wider radial bands (GROWL) with optimally regularized self
      calibration.
AB  - A self-calibrated parallel imaging reconstruction method is proposed for
      azimuthally undersampled radial dataset. A generalized auto-calibrating partially
      parallel acquisition (GRAPPA) operator is used to widen each radial view into a
      band consisting of several parallel lines, followed by a standard regridding
      procedure. Self-calibration is achieved by regridding the central k-space region,
      where Nyquist criterion is satisfied, to a rotated Cartesian grid. During the
      calibration process, an optimal Tikhonov regularization factor is introduced to
      reduce the error caused by the small k-space area of the self-calibration region.
      The method was applied to phantom and in vivo datasets acquired with an eight
      element coil array, using 32-64 radial views with 256 readout samples. When
      compared with previous radial parallel imaging techniques, GRAPPA operator for
      wider radial bands (GROWL) provides a significant speed advantage since
      calibration is carried out using the fully sampled k-space center. A further
      advantage of GROWL is its applicability to arbitrary-view angle ordering schemes.

PMID- 20806378
TI  - Designing adiabatic radio frequency pulses using the Shinnar-Le Roux algorithm.
AB  - Adiabatic pulses are a special class of radio frequency (RF) pulses that may be
      used to achieve uniform flip angles in the presence of a nonuniform B(1) field.
      In this work, we present a new, systematic method for designing high-bandwidth
      (BW), low-peak-amplitude adiabatic RF pulses that utilizes the Shinnar-Le Roux
      (SLR) algorithm for pulse design. Currently, the SLR algorithm is extensively
      employed to design nonadiabatic pulses for use in magnetic resonance imaging and
      spectroscopy. We have adapted the SLR algorithm to create RF pulses that also
      satisfy the adiabatic condition. By overlaying sufficient quadratic phase across
      the spectral profile before the inverse SLR transform, we generate RF pulses that
      exhibit the required spectral characteristics and adiabatic behavior. Application
      of quadratic phase also distributes the RF energy more uniformly, making it
      possible to obtain the same spectral BW with lower RF peak amplitude. The method
      enables the pulse designer to specify spectral profile parameters and the degree
      of quadratic phase before pulse generation. Simulations and phantom experiments
      demonstrate that RF pulses designed using this new method behave adiabatically.

PMID- 20806379
TI  - Image-based calculation of perfusion and oxyhemoglobin saturation in skeletal
      muscle during submaximal isometric contractions.
AB  - The relative oxygen saturation of hemoglobin and the rate of perfusion are
      important physiological quantities, particularly in organs such as skeletal
      muscle, in which oxygen delivery and use are tightly coupled. The purpose of this
      study was to demonstrate the image-based calculation of the relative oxygen
      saturation of hemoglobin and quantification of perfusion in skeletal muscle
      during isometric contractions. This was accomplished by establishing an empirical
      relationship between the rate of radiofrequency-reversible dephasing and near
      infrared spectroscopy-observed oxyhemoglobin saturation (relative oxygen
      saturation of hemoglobin) under conditions of arterial occlusion and constant
      blood volume. A calibration curve was generated and used to calculate the
      relative oxygen saturation of hemoglobin from radiofrequency-reversible dephasing
      changes measured during contraction. Twelve young healthy subjects underwent 300
      s of arterial occlusion and performed isometric contractions of the dorsiflexors
      at 30% of maximal contraction for 120 s. Muscle perfusion was quantified during
      contraction by arterial spin labeling and measures of muscle T(1). Comparisons
      between the relative oxygen saturation of hemoglobin values predicted from
      radiofrequency-reversible dephasing and that measured by near-infrared
      spectroscopy revealed no differences between methods (P = 0.760). Muscle
      perfusion reached a value of 34.7 mL 100 g(-1) min(-1) during contraction. These
      measurements hold future promise in measuring muscle oxygen consumption in
      healthy and diseased skeletal muscle.

PMID- 20806380
TI  - Manganese-enhanced MRI of salivary glands and head and neck tumors in living
      subjects.
AB  - Manganese-enhanced MRI has previously been used for visualization of brain
      architecture and functional mapping of neural pathways. The present work
      investigated the potential of manganese-enhanced MRI for noninvasive imaging of
      salivary glands in living subjects. Marked shortening of T(1) was observed in
      salivary glands of naive mice (n = 5) 24-48 h after systemic administration of
      MnCl(2) (0.4 mmol/kg, intraperitoneally). Three-dimensional MR microscopy
      confirmed selective contrast enhancement of salivary gland tissues post-MnCl(2)
      injection. Ectopic and orthotopic head and neck tumor xenografts also showed an
      increase in R(1) at 24 h following MnCl(2) injection (0.2 mmol/kg,
      intraperitoneally). However, tumor enhancement was minimal compared to salivary
      gland tissue. Salivary gland R(1) values were lower in mice bearing orthotopic
      head and neck tumors compared to naive mice. These results demonstrate, for the
      first time, the usefulness of manganese-enhanced MRI in the visualization of
      salivary glands and head and neck tumors in vivo.

PMID- 20806381
TI  - Standardization of relative cerebral blood volume (rCBV) image maps for ease of
      both inter- and intrapatient comparisons.
AB  - Relative cerebral blood volume (rCBV) measured using dynamic susceptibility
      contrast MRI suffers from interpatient and interstudy variability for the same
      tissue type. Traditionally, when a more quantitative assessment of rCBV is
      required, as for comparison across studies and patients, the rCBV values are
      normalized to the rCBV in a reference region such as normal-appearing white
      matter. However, this technique of normalization is subjective and time consuming
      and introduces user-dependent variability. In this study, we demonstrate that a
      method called standardization, applied to rCBV maps, is an objective means of
      translating all rCBV values to a consistent scale. This approach reduces
      interpatient and interstudy variability for the same tissue type, thus enabling
      easy and accurate visual and quantitative comparison across studies. One caveat
      to this approach is that it is not appropriate for the evaluation of global
      changes in blood volume, since systematic differences are removed in the process
      of standardization.

PMID- 20806382
TI  - Bayesian estimation of changes in transverse relaxation rates.
AB  - Although the biasing of R(2)* estimates by assuming magnitude MR data to be
      normally distributed has been described, the effect on changes in R(2)*
      (DeltaR(2)*), such as induced by a paramagnetic contrast agent, has not been
      reported. In this study, two versions of a novel Bayesian maximum a posteriori
      approach for estimating DeltaR(2)* are described and evaluated: one that assumes
      normally distributed data and the other, Rice-distributed data. The approach
      enables the robust, voxelwise determination of the uncertainty in DeltaR(2)*
      estimates and provides a useful statistical framework for quantifying the
      probability that a pixel has been significantly enhanced. This technique was
      evaluated in vivo, using ultrasmall superparamagnetic iron oxide particles in
      orthotopic murine prostate tumors. It is shown that assuming magnitude data to be
      normally distributed causes DeltaR(2)* to be underestimated when signal-to-noise
      ratio is modest. However, the biasing effect is less than is found in R(2)*
      estimates, implying that the simplifying assumption of normally distributed noise
      is more justifiable when evaluating DeltaR(2)* compared with when evaluating
      precontrast R(2)* values.

PMID- 20806383
TI  - Flexible add-on solution for MR image-guided interventions in a closed-bore
      scanner environment.
AB  - MRI is of great clinical utility for the guidance of various diagnostic and
      therapeutic procedures. In a standard closed-bore scanner, the simplest approach
      is to manipulate the instrument outside the bore and move the patient into the
      bore for reference and control imaging only. Without navigational assistance,
      however, such an approach can be difficult, inaccurate, and time consuming.
      Therefore, an add-on navigation solution is described that addresses these
      limitations. Patient registration is established by an automatic, robust, and
      fast (<30 sec) localization of table-mounted MR reference markers and the
      instrument is tracked optically. Good hand-eye coordination is provided by
      following the virtual instrument on MR images that are reconstructed in real time
      from the reference data. Needle displacements of 2.2 +/- 0.6 mm and 3.9 +/- 2.4
      mm were determined in a phantom (P < 0.05), depending on whether the reference
      markers were placed at smaller (98-139 mm) or larger (147-188 mm) distances from
      the isocenter. Clinical functionality of the navigation concept is demonstrated
      by a double oblique, subscapular hook-wire insertion in a patient with a body
      mass index of 30.1 kg/m(2). Ease of use, compactness, and flexibility of this
      technique suggest that it can be used for many other procedures in different body
      regions. More patient cases are needed to evaluate clinical performance and
      workflow.

PMID- 20806385
TI  - Non-ablative 1,550 nm fractional laser therapy versus triple topical therapy for
      the treatment of melasma: a randomized controlled split-face study.
AB  - BACKGROUND: Melasma is a uichronic, often relapsing skin disorder, with poor long
      term results from all current therapies. OBJECTIVE: To assess efficacy and safety
      of non-ablative 1,550 nm fractional laser therapy (FLT) as compared to the gold
      standard, triple topical therapy (TTT). STUDY DESIGN: Twenty-nine patients with
      melasma were included in a randomized controlled observer-blinded study with
      split-face design. Each side of the face was randomly allocated to either 4-5 non
      ablative FLT sessions (15 mJ/microbeam, 14-20% coverage) or TTT (hydroquinone 5%,
      tretinoin 0.05%, triamcinolone acetonide 0.1% cream). TTT was applied once daily
      for 15 weeks until the last FLT session. After this last treatment, patients were
      asked to apply TTT twice weekly on both sides of the face during follow-up.
      Improvement of melasma was assessed by patient's global assessment (PGA),
      patient's satisfaction, physician's global assessment (PhGA), melanin index, and
      lightness (L-value) at 3 weeks, and at 3 and 6 months after the last treatment.
      RESULTS: Mean PGA and satisfaction were significantly lower at the FLT side
      (P<0.001). PhGA, melanin index, and L-value showed a significant worsening of
      hyperpigmentation at the FLT side. At the TTT side, no significant change was
      observed. At 6 months follow-up, most patients preferred TTT. Side effects of FLT
      were erythema, burning sensation, edema, and pain. Nine patients (31%) developed
      PIH after two or more laser sessions. Side effects of TTT were erythema, burning
      sensation, and scaling. CONCLUSIONS: Given the high rate of postinflammatory
      hyperpigmentation, non-ablative 1,550 nm fractional laser at 15 mJ/microbeam is
      not recommendable in the treatment of melasma. TTT remains the gold standard
      treatment.

PMID- 20806386
TI  - The relationship between protoporphyrin IX photobleaching during real-time
      dermatological methyl-aminolevulinate photodynamic therapy (MAL-PDT) and
      subsequent clinical outcome.
AB  - BACKGROUND AND OBJECTIVE: The relationship between protoporphyrin IX (PpIX)
      photobleaching and cellular damage during aminolevulinic (ALA) photodynamic
      therapy (PDT) has been studied at the cellular level. This study assessed the
      capability of a non-invasive fluorescence imaging system (Dyaderm, Biocam,
      Germany), to monitor changes in PpIX during real time methyl-aminolevulinate
      (MAL) PDT in dermatological lesions, and thus to act as a predictive tool in
      terms of observed clinical outcome post-treatment. MATERIALS AND METHODS:
      Patients attending Royal Cornwall Hospital (Truro, UK) for MAL-PDT to licensed
      lesions (actinic keratosis, Bowen's disease, and basal cell carcinoma) were
      monitored using the pre-validated non-invasive fluorescence imaging system.
      Patients were imaged at three distinct time points: prior to the application of
      MAL, after the 3 hours of MAL application and immediately following light
      irradiation. The fluorescence intensity of the images were analysed with image
      analysis software and the percentage change in fluorescence during light
      irradiation was related to the clinical outcome observed 3 months following
      treatment. In total 100 patients underwent at least one session of MAL-PDT.
      RESULTS: Significantly higher levels of change in PpIX fluorescence during light
      irradiation (P<0.005) were observed in lesions undergoing complete clearance at 3
      months when compared to those patients who underwent partial or no clearance. In
      contrast no significant difference (P>0.500) was observed in the total levels of
      PpIX recorded after MAL application in patients undergoing partial and complete
      clearance at 3 months. CONCLUSIONS: PpIX photobleaching is indicative of the
      level of cellular damage PDT treatment will induce and therefore the clinical
      outcome expected within patients. This study indicated the potential of the
      commercially available fluorescence imaging system investigated to predict
      treatment success at the time of light irradiation and in the future it may be
      possible to employ it to individualise treatment parameters to improve
      dermatological PDT efficacy/outcome.

PMID- 20806387
TI  - Thulium laser urethrotomy for urethral stricture: a preliminary report.
AB  - BACKGROUND AND OBJECTIVES: The outcome of thulium laser urethrotomy for patients
      with urethral stricture had not been reported. The purpose of this study was to
      evaluate outcome of endourethrotomy with the thulium laser as a minimally
      invasive treatment for urethral stricture. MATERIALS AND METHODS: Twenty-one
      consecutive patients with urethral stricture were evaluated by retrograde
      uroflowmetry, International Prostate Symptom Score (IPSS), and quality of life
      preoperatively at a single academic center. All patients were treated with
      thulium laser urethrotomy. All patients were followed up for 12-24 months
      postoperatively by uroflowmetry and by retrograde with voiding cystourethrogram
      every 3 months. And all patients were followed up by mailed questionnaire,
      including IPSS and quality of life. RESULTS: Retrograde endoscopic thulium laser
      urethrotomy was performed in all 21 patients. Most patients (N = 16; 76.2%) did
      not need any reintervention. Five patients developed recurrent strictures, of
      them two patients were treated by another laser urethrotomy, one patient was
      treated by open urethroplasty with buccal mucosa and the other two patients'
      reintervention were treated by urethral dilation. No intraoperative complications
      were encountered, although in 9.5% (N = 2) of patients, a urinary tract infection
      was diagnosed postoperatively. No gross hematuria occurred. Including two
      patients treated with repeat laser urethrotomy, 17(81.0%) showed good flow of
      urine (Q(ave)>16.0 ml/second) and adequate caliber urethra in retrograde
      urethrogram (RGU) 12 months after operation. Three (14.3%) patients showed narrow
      stream of urine (Q(ave)<8.0 ml/second) and urethral dilation was done every month
      or 2 months. There was one patient whose Q(ave) was between 8.0 and 16.0
      ml/second. And this patient was treated by neither urethral dilation nor another
      laser urethrotomy. CONCLUSIONS: The thulium laser urethrotomy was a safe and
      effective minimally invasive therapeutic modality for urethral stricture.

PMID- 20806388
TI  - GreenLight HPS laser 120-W versus diode laser 200-W vaporization of the prostate:
      comparative clinical experience.
AB  - BACKGROUND AND OBJECTIVE: We present our clinical experiences of two recently
      introduced vaporization laser systems: the GreenLight High Performance System
      (HPS) laser (532 nm, 120 W) and the Diolas LFD diode laser (980 nm, 200 W).
      MATERIALS AND METHODS: Two laser systems were evaluated to compare their clinical
      results for the treatment of benign prostatic hyperplasia (BPH). Patients were
      treated using either the GreenLight HPS laser (n = 84) or the diode laser (n =
      55) in a prospective randomized study. The data of International Prostate Symptom
      Score (IPSS), maximum flow rate (Q(max)), post-void residual urine (PVR), and
      quality of life score (Qols) were recorded at baseline, 1-, 6-, and 12-month
      follow-ups. The prostate volume and prostate-specific antigen (PSA) level were
      assessed at baseline and 6-month follow-up. All complications were also recorded.
      RESULTS: There was a statistically significant difference in IPSS, Q(max), PVR,
      and QoLs in each laser group at the 1-, 6-, and 12-month follow-ups compared with
      baseline. There was no statistical significant difference in any of these
      parameters at any follow-up interval between each group. The diode laser
      demonstrates superior hemostatic properties compared with the GreenLight HPS
      laser. Postoperative incontinence and postoperative irritative symptoms are more
      pronounced (P < 0.05) after diode laser prostatectomy. Higher incidence of
      dysuria with sloughing tissues and epididymitis (P < 0.05) is noted after diode
      laser prostatectomy. Other complications were comparable for both procedures.
      CONCLUSIONS: Although both lasers can improve subjective and objective parameters
      of BPH, both can produce undesired effects. The search for the ideal vaporization
      laser to treat BPH still continues.

PMID- 20806389
TI  - In vivo femtosecond laser subsurface scleral treatment in rabbit eyes.
AB  - BACKGROUND AND OBJECTIVES: The progression of glaucoma can be reduced or delayed
      by reducing intraocular pressure (IOP). The properties of femtosecond laser
      surgery, such as markedly reduced collateral tissue damage, coupled with the
      ability to achieve isolated subsurface surgical effects in the sclera, make this
      technology a promising candidate in glaucoma management. In this pilot study we
      demonstrate the in vivo creation of partial thickness subsurface drainage
      channels with the femtosecond laser in the sclera of rabbit eyes in order to
      increase aqueous humor (AH) outflow. STUDY DESIGN/MATERIALS AND METHODS: A
      femtosecond laser beam tuned to a 1.7 microm wavelength was scanned along a
      rectangular raster pattern to create the partial thickness subsurface drainage
      channels in the sclera of one eye of each of the four rabbits included in this
      pilot study. IOP was measured before and 20 minutes after the laser treatment to
      evaluate the acute effect of the procedure. RESULTS: OCT images verified the
      creation of the partial thickness subsurface scleral channels in the eyes of the
      in vivo rabbits. Comparison of pre- and postoperative IOP measurements in treated
      and control eyes revealed a reduction in the intraocular pressure due to the
      increased rate of AH outflow resulted in by the presence of the partial thickness
      scleral channels. CONCLUSIONS: The creation of partial thickness subsurface
      drainage channels was demonstrated in the sclera of in vivo rabbit eyes with a
      1.7 microm wavelength femtosecond laser. Reduction in IOP achieved by the partial
      thickness channels suggests potential utility in the treatment of elevated IOP.

PMID- 20806390
TI  - Comparison of Er:YAG laser, piezoelectric, and drill osteotomy for dental implant
      site preparation: a biomechanical and histological analysis in sheep.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to examine the influence of
      implant bed preparation, using either Er:YAG laser ablation, piezoelectric
      surgery or drill osteotomy, on osseointegration of titanium dental implants after
      4, 6, and 8 weeks. MATERIAL AND METHODS: A total of 108 implants (Camlog) were
      placed in the pelvis of 6 sheep (18 implants/sheep). Implant sites were prepared
      by an Er:YAG laser, a dental drill or a piezoelectric device. For each time
      period, six implants were used for biomechanical removal torque testing and six
      implants for a semi-quantitative histological assessment of the bone-to-implant
      contact (BIC). RESULTS: An initially missing implant adjusted site preparation
      led to slightly higher BIC and torque values in the piezoelectric and laser
      groups due to a press-fit effect after 4 weeks. Statistical analysis of the
      average mean BIC after 4, 6, and 8 weeks revealed no significant differences (P >
      0.05) between the different osteotomy techniques. Comparison of individual
      removal torque values showed the highest value for laser osteotomy after 8 weeks
      (1,698.50 +/- 67.52 Nmm), which was significantly higher than the corresponding
      value for drill osteotomy (P = 0.006). CONCLUSION: Although BIC and removal
      torque values decreased in the laser and piezoelectric groups at 6 weeks during
      an active remodeling process, favorable and superior BIC as well as torque values
      could be demonstrated at 8 weeks. Thus laser and piezoelectric osteotomy seem to
      be at least comparable to drill osteotomy, concerning early osseointegration and
      implant stability.

PMID- 20806391
TI  - Micromorphology of resin-dentin interfaces using one-bottle etch&rinse and self
      etching adhesive systems on laser-treated dentin surfaces: a confocal laser
      scanning microscope analysis.
AB  - BACKGROUND AND OBJECTIVES: This study evaluated the hybrid layer (HL) morphology
      created by three adhesive systems (AS) on dentin surfaces treated with Er:YAG
      laser using two irradiation parameters. STUDY DESIGN: Occlusal flat dentin
      surfaces of 36 human third molars were assigned into nine groups (n = 4)
      according to the following ASs: one bottle etch&rinse Single Bond Plus (3M ESPE),
      two-step Clearfil Protect Bond (Kuraray), and all-in-one S(3) Bond (Kuraray) self
      etching, which were labeled with rhodamine B or fluorescein isothiocyanate
      dextran and were applied to dentin surfaces that were irradiated with Er:YAG
      laser at either 120 (38.7 J/cm(2)) or 200 mJ/pulse (64.5 J/cm(2)), or were
      applied to untreated dentin surfaces (control group). The ASs were light
      activated following MI and the bonded surfaces were restored with resin composite
      Z250 (3M ESPE). After 24 hours of storage in vegetable oil, the restored teeth
      were vertically, serially sectioned into 1-mm thick slabs, which had the adhesive
      interfaces analyzed with confocal laser microscope (CLSM-LSM 510 Meta). CLSM
      images were recorded in the fluorescent mode from three different regions along
      each bonded interface. RESULTS: Non-uniform HL was created on laser-irradiated
      dentin surfaces regardless of laser irradiation protocol for all AS, while
      regular and uniform HL was observed in the control groups. "Stretch mark"-like
      red lines were found within the HL as a result of resin infiltration into dentin
      microfissures, which were predominantly observed in 200 mJ/pulse groups
      regardless of AS. Poor resin infiltration into peritubular dentin was observed in
      most regions of adhesive interfaces created by all ASs on laser-irradiated
      dentin, resulting in thin resin tags with neither funnel-shaped morphology nor
      lateral resin projections. CONCLUSION: Laser irradiation of dentin surfaces at
      120 or 200 mJ/pulse resulted in morphological changes in HL and resin tags for
      all ASs evaluated in the study.

PMID- 20806393
TI  - Differential mechanisms for the inhibition of human cytochrome P450 1A2 by
      apigenin and genistein.
AB  - The inhibitory effects of flavonoids on the human cytochrome P450 1A2 (CYP1A2)
      were examined. Among flavonoids tested, galangin, kaempferol, chrysin, and
      apigenin were potent inhibitors. Although apigenin belonging to flavones and
      genistein belonging to isoflavones are similar in the chemical structures, the
      inhibitory potencies for CYP1A2 were distinguished markedly between these two
      flavonoids. In computer-docking simulation, apigenin interacted with the same
      mode of cocrystallized alpha-naphthoflavone in the active site of CYP1A2, and
      then the B ring of apigenin was placed close to the heme iron of the enzyme with
      a single orientation. In contrast, the docked genistein conformation showed two
      different binding modes, and the A ring of genistein was oriented to the heme
      iron of CYP1A2. Furthermore, the binding free energy of apigenin was lower than
      that of genistein. These results demonstrate a possible mechanism that causes the
      differential inhibitory potencies of apigenin and genistein for CYP1A2.

PMID- 20806394
TI  - Protective effect of edaravone against PrP106-126-induced PC12 cell death.
AB  - The prion protein peptide PrP106-126 induces cell apoptosis through mechanisms
      involving production of intracellular reactive oxygen species. The present study
      investigated the effects of edaravone, a potent free radical scavenger in
      clinical use, on cell cytotoxicity induced by PrP106-126. Results showed that
      PrP106-126 decreased PC12 cell viability in a dose- and time-dependent manner.
      Edaravone significantly antagonized the cytotoxic effects of PrP106-126.
      Mechanistically, PrP106-126 decreased PC 12 intracellular glutathione (GSH)
      concentrations, decreased superoxide dismutase (SOD) enzyme activity, increased
      concentrations of the oxidation end product malondialdehyde (MDA), depolarized
      the mitochondrial membrane, and increased caspase-3 activity. Edaravone alone did
      not affect GSH, SOD, or MDA but did effectively reverse all of the intracellular
      prooxidant effects induced by PrP106-126 and inhibit induced apoptosis in PC12
      cells. In conclusion, edaravone may be a viable candidate for the treatment of
      oxidative stress-induced neurodegenerative disease.

PMID- 20806395
TI  - Effects of corticosterone and 2,3,7,8-tetrachloro- dibenzo-p-dioxin on epididymal
      antioxidant system in adult rats.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an endocrine disruptor, causes
      epididymal toxicity by inducing oxidative stress. Glucocorticoids have been found
      to influence TCDD action in vitro and in vivo. The present experiments were set
      up to analyze the effects of TCDD on rat epididymal antioxidant system under the
      influence of increased corticosterone level. Adult male Wistar/NIN rats (70-80
      days old) numbering 24 (six per group) were used in the study. Corticosterone (3
      mg/kg body weight per day) or TCDD (100 ng/kg body weight per day) were
      administered or coadministered to rats for 15 days. Treatment with corticosterone
      or TCDD decreased the levels of serum testosterone significantly. In caput,
      corpus, and cauda fractions, administration of corticosterone or TCDD increased
      the levels of lipid peroxidation and hydrogen peroxide and decreased the
      activities of superoxide dismutase and catalase significantly. Coadministration
      of corticosterone and TCDD to rats decreased the levels of serum testosterone
      significantly as compared with rats treated with TCDD alone. In caput, corpus,
      and cauda fractions, the levels of lipid peroxidation and hydrogen peroxide were
      increased and activities of superoxide dismutase and catalase were decreased
      significantly as compared with rats treated with TCDD alone. Stress,
      characterized by increased glucocorticoid levels and activity, may enhance TCDD
      induced epididymal toxicity.

PMID- 20806397
TI  - Muscle-selective block using intrafascicular high-frequency alternating current.
AB  - High-frequency alternating current (HFAC) applied to a peripheral nerve can
      reversibly block skeletal muscle contractions. We evaluated the ability of HFAC
      delivered via intrafascicular electrodes to selectively block activation of
      targeted muscles without affecting activation of other muscles. Utah slanted
      electrode arrays (USEAs) were implanted into the sciatic nerves of five cats, and
      HFAC was delivered to individual USEA electrodes. The effects of HFAC block were
      monitored by recording evoked electromyograms (EMGs) and three-dimensional
      endpoint forces. In each animal, activity evoked in targeted muscles by nerve
      cuff stimulation could be selectively abolished by HFAC delivered via individual
      USEA electrodes. Two mechanisms of blockade were evoked: selective neuromuscular
      blocks were achieved with 500-8000-HZ HFAC, and selective nerve conduction block
      was achieved in one animal using 16-kHZ HFAC. These results show that
      intrafascicular HFAC can be used to block selected muscles independent of
      activation of other muscles.

PMID- 20806399
TI  - Qualifications for practitioners of neuromuscular ultrasound: position statement
      of the American Association of Neuromuscular and Electrodiagnostic Medicine.

PMID- 20806398
TI  - Broadening the spectrum of controls for skin biopsy in painful neuropathies.
AB  - Epidermal nerve fiber density (ENFD) is useful in the evaluation of small-fiber
      neuropathies (SFSNs). A recent evidence-based review highlighted the need to
      broaden the spectrum of ENFD controls to include lower limb pain states other
      than polyneuropathy. We studied epidermal innervation in multiple sclerosis (MS)
      and distal lower limb burning pain (DLLBP). Distal-leg ENFD/morphology in MS
      DLLBP patients did not differ significantly from that of healthy controls. This
      study extends the range of ENFD controls and further supports use of ENFD
      assessment in SFSN.

PMID- 20806400
TI  - Seipin S90L mutation in an Italian family with CMT2/dHMN and pyramidal signs.
AB  - Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2)
      gene have been associated with different clinical phenotypes including Silver
      syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and
      Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement. We
      studied an Italian family with a CMT2 phenotype with pyramidal signs that had
      subclinical sensory involvement on sural nerve biopsy. Direct sequencing analysis
      of the BSCL2 gene in the three affected siblings revealed an S90L mutation. This
      report confirms the variability of clinical phenotypes associated with a BSCL2
      Ser90Leu mutation and describes the first Italian family with this mutation.

PMID- 20806403
TI  - A comparison of multiple imputation and fully augmented weighted estimators for
      Cox regression with missing covariates.
AB  - Several approaches exist for handling missing covariates in the Cox proportional
      hazards model. The multiple imputation (MI) is relatively easy to implement with
      various software available and results in consistent estimates if the imputation
      model is correct. On the other hand, the fully augmented weighted estimators
      (FAWEs) recover a substantial proportion of the efficiency and have the doubly
      robust property. In this paper, we compare the FAWEs and the MI through a
      comprehensive simulation study. For the MI, we consider the multiple imputation
      by chained equation and focus on two imputation methods: Bayesian linear
      regression imputation and predictive mean matching. Simulation results show that
      the imputation methods can be rather sensitive to model misspecification and may
      have large bias when the censoring time depends on the missing covariates. In
      contrast, the FAWEs allow the censoring time to depend on the missing covariates
      and are remarkably robust as long as getting either the conditional expectations
      or the selection probability correct due to the doubly robust property. The
      comparison suggests that the FAWEs show the potential for being a competitive and
      attractive tool for tackling the analysis of survival data with missing
      covariates.

PMID- 20806405
TI  - Phosphorylation of ERK in the spinal dorsal horn following pancreatic
      pronociceptive stimuli with proteinase-activated receptor-2 agonists and hydrogen
      sulfide in rats: evidence for involvement of distinct mechanisms.
AB  - Noxious stimuli cause prompt phosphorylation of extracellular signal-regulated
      kinase (ERK) in the spinal dorsal horn that contributes to facilitation of pain
      sensation and is often used as an immediate marker for excitation of spinal
      neurons following somatic and colonic nociception. Here we asked whether two
      distinct pronociceptive stimuli with proteinase-activated receptor-2 (PAR2)
      agonists and hydrogen sulfide (H(2)S) in the pancreas cause phosphorylation of
      ERK in the spinal dorsal horn and also examined involvement of their possible
      downstream signaling molecules, transient receptor potential vanilloid-1 (TRPV1)
      and T-type Ca(2+) channels, respectively. Capsaicin (a TRPV1 agonist), trypsin
      (an endogenous PAR2 agonist), SLIGRL-NH(2) (a PAR2-activating peptide), and NaHS
      (an H(2)S donor) were infused into the pancreatic duct in anesthetized rats, and
      phosphorylated ERK in the spinal cord was detected by immunohistochemistry.
      Intraductal administration of capsaicin and trypsin caused prompt phosphorylation
      of ERK in the superficial layers of T9, but not T5 or T12, spinal dorsal horn.
      SLIGRL-NH(2) and NaHS, administered in the same manner, also produced ERK
      phosphorylation in the corresponding spinal regions. Mibefradil, a T-type Ca(2+)
      channel blocker, abolished the phosphorylation of ERK caused by intraductal NaHS
      but not SLIGRL-NH(2). In contrast, capsazepine, an inhibitor of TRPV1, suppressed
      the phosphorylation of ERK caused by intraductal SLIGRL-NH(2) but not NaHS. Our
      data thus demonstrate that pancreatic pronociceptive stimuli with PAR2 agonists
      and H(2)S cause ERK phosphorylation in the spinal dorsal horn, through activation
      of TRPV1 and T-type Ca(2+) channels, respectively, and that those two
      pronociceptive pathways are independent of each other.

PMID- 20806404
TI  - On the mechanism of protein fold-switching by a molecular sensor.
AB  - Alternate frame folding (AFF) is a mechanism by which conformational change can
      be engineered into a protein. The protein structure switches from the wild-type
      fold (N) to a circularly-permuted fold (N'), or vice versa, in response to a
      signaling event such as ligand binding. Despite the fact that the two native
      states have similar structures, their interconversion involves folding and
      unfolding of large parts of the molecule. This rearrangement is reported by
      fluorescent groups whose relative proximities change as a result of the order
      disorder transition. The nature of the conformational change is expected to be
      similar from protein to protein; thus, it may be possible to employ AFF as a
      general method to create optical biosensors. Toward that goal, we test basic
      aspects of the AFF mechanism using the AFF variant of calbindin D(9k). A simple
      three-state model for fold switching holds that N and N' interconvert through the
      unfolded state. This model predicts that the fundamental properties of the switch
      -calcium binding affinity, signal response (i.e., fluorescence change upon
      binding), and switching rate--can be controlled by altering the relative
      stabilities of N and N'. We find that selectively destabilizing N or N' changes
      the equilibrium properties of the switch (binding affinity and signal response)
      in accordance with the model. However, kinetic data indicate that the switching
      pathway does not require whole-molecule unfolding. The rate is instead limited by
      unfolding of a portion of the protein, possibly in concert with folding of a
      corresponding region.

PMID- 20806406
TI  - Reduction of hippocampal N-acetyl aspartate level in aged APP(Swe)/PS1(dE9)
      transgenic mice is associated with degeneration of CA3 pyramidal neurons.
AB  - Age-related metabolic changes in the hippocampus of APP(Swe)/PS1(dE9) mice were
      measured with long echo-time in vivo (1)H-magnetic resonance spectroscopy ((1)H
      MRS). Thioflavine S staining and Nissl staining were used to characterize
      deposition of Abeta aggregates and neuronal degeneration in the transgenic
      animals, respectively. The results showed that the APP(Swe)/PS1(dE9) mice had
      significantly decreased hippocampal N-acetyl aspartate (NAA)/total creatine (tCr)
      level at 16 months of age, which was associated with degeneration of and
      intracellular deposition of thioflavine S-positive materials in hippocampal CA3
      pyramidal neurons. The results of this study provide direct evidence showing
      association among Abeta pathology (intracellular deposition of thioflavine S
      positive materials), neuronal degeneration, and metabolic changes observable with
      in vivo (1)H-MRS in the hippocampus of APP(Swe)/PS1(dE9) mice.

PMID- 20806407
TI  - Localized alteration of microtubule polymerization in response to guidance cues.
AB  - Inhibition of microtubule dynamic instability prevents growth cone turning in
      response to guidance cues, yet specific changes in microtubule polymerization as
      growth cones encounter boundaries have not been investigated. In this study, we
      examined the rate and direction of microtubule polymerization in response to
      soluble nerve growth factor (NGF) and immobilized chondroitin sulfate
      proteoglycans (CSPGs) by expressing enhanced GFP-EB3 in rat pheochromocytoma
      (PC12) cells. GFP-EB3 comets were monitored in live cells using time-lapse
      epifluorescent microscopy. With an automated tracking system, the rate of
      microtubule polymerization was calculated as the frame-to-frame displacement of
      EB3 comets. Our results demonstrate that the rate of microtubule polymerization
      is increased following NGF treatment, whereas contact with CSPGs decreases
      microtubule polymerization rates. This reduction in microtubule polymerization
      rates was specifically localized to neurites in direct contact with CSPGs and not
      at noncontacting neurites. Additionally, we found an increase in the percentage
      of microtubules polymerizing in the retrograde direction in neurites at CSPG
      boundaries, with a concomitant decrease in the rate of retrograde microtubule
      polymerization. These results implicate localized changes in microtubule dynamics
      as an important component of the growth cone response to guidance cues.

PMID- 20806409
TI  - Aberrant stress-induced Hsp70 expression in immune cells in multiple sclerosis.
AB  - Heat shock protein 70 (Hsp70), a prominent member of the heat shock protein
      family, is a stress-induced chaperone, contributing to the "protein triage"
      mechanism. However, we and others have previously shown that chaperonin activity
      of Hsp70 also promotes immune recognition of protein/peptide antigens, including
      myelin autoantigens. Hsp70 has been strikingly elevated in multiple sclerosis
      (MS) lesions. In a search for the mechanism of Hsp70 up-regulation in MS, we
      analyzed Hsp70 expression in peripheral blood mononuclear cells (PBMCs) from MS
      patients (n = 49), healthy controls (n = 40), and patients with rheumatoid
      arthritis, (RA; n = 13). Hsp70 was detected by Western blot, and Hsp70 levels
      were quantified by ELISA. We found that Hsp70 was expressed at low levels in ex
      vivo PBMCs. However, after heat shock, Hsp70 was up-regulated significantly more
      (up to sixfold) in MS patients compared with healthy controls. This significant
      overproduction of Hsp70 was also seen following another stress condition, LPS
      stimulation. Hsp70 is a product of several independent genes, and we found the
      HSPA1B gene product to be the major form responsible for Hsp70 protein
      overexpression in PBMCs. Hsp70 overexpression was preceded by increased nuclear
      presence of heat shock factor 1 (HSF1). HSF1 activation depends on
      phosphorylation, and we found that inhibition of the A group of protein kinase C
      isoenzymes significantly reduced inducible Hsp70 production. These results
      indicate that immune cells from MS patients are more prone to Hsp70 induction
      under stress conditions, suggesting a possible link between Hsp70 overexpression
      and development of autoimmunity.

PMID- 20806408
TI  - L10p and P158DEL DJ-1 mutations cause protein instability, aggregation, and
      dimerization impairments.
AB  - A variety of mutations in the gene encoding DJ-1 protein cause autosomal
      recessive early-onset parkinsonism. Recently, a novel pathogenic homozygous DJ-1
      missense mutation resulting in the L10P amino acid substitution was reported. In
      a separate study, a novel homozygous mutation resulting in the deletion of DJ-1
      residue P158 was also reported to be causative of disease. The specific effects
      of the novel L10P and P158DEL mutations on protein function have not been
      studied. Here, L10P and P158DEL DJ-1 proteins were assessed for protein
      stability, dimerization, solubility, subcellular localization, and protective
      function in comparison with WT and the L166P DJ-1 pathogenic variant. It was
      discovered that, compared with WT protein, L10P, L166P, and P158DEL DJ-1 variants
      exhibited dramatically reduced protein stabilities. Degradation of each of the
      pathogenic mutants appeared to be mediated in part by the proteasome.
      Interestingly, unlike L166P DJ-1, the L10P and P158DEL DJ-1 variants retained the
      ability to dimerize with WT DJ-1 protein; however, neither of these mutants was
      able to form homodimers. Additionally, the L10P, L166P, and P158DEL DJ-1 variants
      exhibited altered profiles on size-exclusion chromatography and demonstrated
      reduced solubilities in comparison with WT protein, and the latter aberration
      could be exacerbated in the presence of MG-132. Furthermore, cells stably
      expressing L10P DJ-1 were more vulnerable to treatments with proteasome
      inhibitors, suggesting that L10P DJ-1 may be toxic to cells under conditions of
      proteasome stress. Taken together, these findings suggest that diverse aberrant
      mechanisms, including alterations in protein stability and protein folding, are
      associated with the pathogenicity of the L10P and P158DEL DJ-1 variants.

PMID- 20806410
TI  - I(h) "run-up" in rat neocortical neurons and transiently rat or human HCN1
      expressing HEK293 cells.
AB  - Hyperpolarization-activated cyclic nucleotide-gated ion channels (HCN) are key
      determinants of CNS functions. Here we describe an increase in hyperpolarization
      activated current (I(h)) at the beginning of whole-cell recordings in rat layer 5
      cortical neurons. For a closer investigation of this I(h) increase, we
      overexpressed the predominant layer 5 rat subunit HCN1 in HEK293 cells. We
      characterized the resulting I(h) in the cell-attached and whole-cell
      configurations. Breaking into whole-cell configuration led to about a 30%
      enhancement of rat HCN1-mediated I(h) accompanied by a depolarizing shift in
      voltage dependence and an accelerated time course of activation. This current
      enhancement is not species specific; for human HCN1, the current similarly
      increases in amount and kinetics. Although the changes were bound to cytosolic
      solution exchange, they were independent of cAMP, ATP, GTP, and the phosphate
      group donor phosphocreatine. Together, these data provide a characterization of
      heterologous expression of rat HCN1 and suggest that cytosolic contents suppress
      I(h). Such a mechanism might constitute a reserve in h-channel function in vivo.

PMID- 20806411
TI  - Up-regulation of erythropoietin receptor by nitric oxide mediates hypoxia
      preconditioning.
AB  - Erythropoietin (Epo), known to stimulate erythroid progenitor cell survival,
      proliferation, and differentiation, has been shown to be neuroprotective against
      brain ischemia in animal models. Both Epo and Epo receptor (EpoR) are expressed
      in the brain and are up-regulated by hypoxia. Brain Epo signaling can stimulate
      neural cell survival and prevent neuron apoptosis. Neurons from EpoR null mice
      exhibit marked increased sensitivity to hypoxia. In endothelial cells, Epo has
      been shown to stimulate nitric oxide (NO) production, particularly at low pO(2).
      We found here that the EpoR expression on neural cells and Epo's neuroprotective
      effect were regulated by NO. Hypoxia increased NO production as well as EpoR
      expression, and inhibition of NOS activity reduced the proportion of EpoR
      expressing neurons induced at low pO(2). Conversely, addition of NO donor to
      cultures grown under normoxia induced EpoR. Similarly, NO donor increased EpoR
      promoter activity in a reporter gene assay, suggesting that NO regulates EpoR at
      the transcription level. Preincubation of neurons with NO results in induction of
      EpoR, which gives rise to protection against hypoxia even in the absence of
      exogenous Epo, although at high concentration NO is toxic. These data provide
      evidence of a role for NO in Epo activity in brain and suggest links between NO
      production, EpoR expression, and Epo signaling in neuroprotection.

PMID- 20806412
TI  - Persistent neural activity regulates Arc/Arg3.1 transcription in the dentate
      gyrus.
AB  - The activity-regulated cytoskeleton-associated gene (Arc, also known as Arg3.1)
      is an effector immediate-early gene rapidly induced by strong neural activity.
      Although a number of studies have revealed significant functions of Arc and Arc
      has come into widespread use as a neural activity marker in behavioral studies,
      the mechanisms regulating Arc transcription remain unclear. Here, we examined the
      conditions of Arc transcription in acute slices of dentate gyrus. Surprisingly,
      kainic acid (1 MUM to 10 mM) application to slices did not induce Arc
      transcription, although intraperitoneal injection of kainic acid (20 mg/kg)
      induced robust Arc transcription. No types of high-frequency stimulation examined
      induced Arc transcription in acute slices. These findings indicate that Arc
      transcription is dramatically suppressed in acute slices of the dentate gyrus, in
      which background neural activity is markedly reduced. Burst stimulation increased
      the number of Arc-expressing cells in the presence of picrotoxin, in which
      excitation was maintained even after the end of stimulation. Moreover, the
      involvement of background neural activity in Arc transcription was tested by
      application of carbachol, a muscarinic receptor agonist. Carbachol also increased
      the number of Arc-expressing cells, which was blocked by atropine, a muscarinic
      receptor antagonist. Taken together, these findings suggest that persistent
      background activity is critical for Arc transcription.

PMID- 20806413
TI  - Decline of thyroid hormones following preoperative therapeutic plasma exchange
      for stabilization of thyrotoxicosis.

PMID- 20806414
TI  - Hematologic and hemostatic changes induced by different columns during LDL
      apheresis.
AB  - Low density lipoprotein (LDL) apheresis is a long-term treatment and its impact
      on risk factors other than lipoproteins could be of importance. Three patients
      with familial hypercholesterolemia participated in six consecutive treatments
      with three different LDL apheresis columns in random order: DL-75, LA-15, and EC
      50W. We compared treatment effects on hemoglobin, leukocytes, platelets,
      fibrinogen, thrombin-antithrombin complexes (TAT), plasminogen activator
      inhibitor-1 (PAI-1), and homocysteine. Hemoglobin, leukocytes and platelets
      decreased significantly with DL-75 (P < 0.05). Hemoglobin and leukocytes
      increased significantly with LA-15 and EC-50W (P < 0.05). Platelets were
      unchanged. The DL-75 column was statistically different from LA-15 and EC-50W
      regarding these parameters. With the columns DL-75, LA-15, and EC-50W fibrinogen
      decreased significantly by 28%, 32%, and 42%, PAI-1 decreased significantly by
      72%, 58%, and 30% while TAT increased significantly by 138%, 3%, and 251%,
      respectively (P < 0.05 for all). When comparing the columns there were
      significant differences between all of them regarding fibrinogen, no differences
      regarding TAT and a difference between DL-75 and EC-50W regarding PAI-1. With the
      columns DL-75, LA-15 and EC-50W homocysteine decreased 22%, 9%, and 13%,
      respectively, but there were no inter column differences. In conclusion, the
      three LDL apheresis columns affected important hematological and hemostatic risk
      factors differently.

PMID- 20806415
TI  - Safety and tolerability of a modified filter-type device for leukocytapheresis
      using ACD-A as anticoagulant in patients with mild to moderately active
      ulcerative colitis. Results of a pilot study.
AB  - CellsorbaTM is a medical device for leukocytapheresis (LCAP) treatment of
      ulcerative colitis (UC). CellsorbaTM EX Global type has been developed from
      Cellsorba E for intended use with ACD-A as anticoagulant. We evaluated safety and
      efficacy of the modified Cellsorba using ACD-A in a pilot trial comprising
      patients with active UC, despite receiving 5-ASA. A total of 10 LCAP
      treatments/patients were administered. Safety assessment focused on clinical
      signs and symptoms, hematological variables, as well as levels of bradykinin and
      IL-6. Efficacy was determined using the Mayo clinical/endoscopic scoring index as
      well histological assessment of biopsies. Additional aim was to evaluate the
      impact of apheresis system lines and filter on selected regulatory molecules. All
      six subjects completed the trial without any serious adverse events. WBC,
      platelet counts, and levels of bradykinin and IL-6 were not significantly
      affected. The median Mayo score decreased from 8.0 to 3.5 at week 8 (and to 2 at
      week 16 for the responders). Four patients were responders, of whom two patients
      went into remission. Median histological scores decreased from 3.5 to 2.0 in
      these four patients. Concentration of LL-37 increased within the apheresis system
      lines. LCAP with Cellsorba EX using ACD-A as anticoagulant was found to be a safe
      and well-tolerated procedure in patients with active UC. The positive impact on
      efficacy parameters merits further evaluation in a controlled fashion.

PMID- 20806416
TI  - Anaphylactoid-like reactions in a patient with HyperLp(a)lipidemia undergoing LDL
      apheresis with dextran sulfate adsorption and herbal therapy with the spice
      turmeric.
AB  - Elevated Lipoprotein (a) (Lp(a)) levels are associated with atherosclerosis and
      are independent risk factors for coronary artery disease and stroke [Ariyo et
      al., N Engl J Med 2003;349:2108-2115; Price et al., Atherosclerosis 2001;157:241
      249]. Low-density lipoprotein (LDL)-apheresis is the most effective therapy for
      reducing Lp(a) levels [Parker, Chem Phys Lipids 1994;67-68:331-338; Stefanutti et
      al., Transfus Apher Sci 2010;42:21-26]. Dextran sulfate-cellulose adsorption
      (Liposorber(r)) removes both LDL and Lp(a) particles with minimal effect on high
      density lipoprotein levels. During the procedure, high levels of bradykinin are
      generated as the kallikrein-kinin system is activated by contact with the
      negatively charged dextran-sulfate cellulose [Krieter et al., Artif Organs
      2005;29:47-52]. Bradykinin is a potent vasodilator and a substrate of the
      angiotension converting enzyme (ACE). ACE inhibitors are contraindicated for
      apheresis procedures because these drugs prevent bradykinin degradation, which
      causes anaphylatoid reactions characterized by hypotension, bradycardia, dyspnea,
      and flushing [Owen and Brecher, Transfusion 1994;34:891-894]. Turmeric is a
      yellow spice that is used as an herbal remedy to treat a myriad of conditions
      ranging from abdominal pain to pulmonary infections. Scientific investigations of
      the ethnomedicinal properties of curcumin, the major derivative of turmeric,
      suggest that this compound has anti-inflammatory, antioxidant, and antineoplastic
      properties [Lobo et al., J Pharm Pharmacol 2009;61:13-21]. We report a case of a
      patient undergoing Liposorber(r) therapy for treatment of hyperLp(a)lipidemia who
      had three episodes of anaphylactoid-like reactions after starting therapy with
      the spice turmeric.

PMID- 20806417
TI  - Iron chelation by cranberry juice and its impact on Escherichia coli growth.
AB  - The various health benefits of Vaccinium macrocarpon (cranberry) are well
      documented and have been attributed mainly to its antioxidant capacity and anti
      adhesive activity. Several different mechanisms have been proposed to explain the
      possible role of cranberries, cranberry juice, and cranberry extracts in
      inhibiting bacterial growth. These mechanisms of action (i.e., inhibition of the
      microbial growth) have not been thoroughly studied. Here, we took advantage of
      current advances in microarray technology and used GeneChip(r) Escherichia coli
      genome 2.0 arrays to gain insight into the molecular mechanisms involved in the
      impact of cranberry juice on the properties of E. coli growth. The inclusion of
      cranberry juice in bacterial growth media was found to significantly impact the
      doubling time of E. coli. The gene expression results revealed altered expression
      of genes associated with iron transport and essential metabolic enzymes as well
      as with adenosine triphosphate (ATP) synthesis and fumarate hydratase in these
      cultures. The altered expression of genes associated with iron transport was
      consistent with the strong iron chelating capability of proanthocyanidins, a
      major constituent of cranberry juice. The iron depletion effect was confirmed by
      adding exogenous iron to the growth media. This addition partially reversed the
      inhibitory effect on bacterial growth observed in the presence of cranberry
      juice/extracts.

PMID- 20806418
TI  - Acceptance of pain, self-compassion and psychopathology: using the chronic pain
      acceptance questionnaire to identify patients' subgroups.
AB  - The present study explores whether specific subgroups of patients could be
      identified based on Chronic Pain Acceptance Questionnaire scores. A battery of
      self-report questionnaire was used to assess acceptance of pain, self-compassion
      and psychopathology in 103 participants with chronic pain, from Portuguese health
      care units. K-Means cluster were performed and the results supported three
      subgroups of patients (low acceptance subgroup; high acceptance subgroup;
      intermediate subgroup with activity engagement near to the mean and low
      willingness to pain). One-way ANOVA's showed that the three subgroups identified
      differed significantly from each other on psychopathology and self-compassion.
      Results indicated that the intermediate subgroup presented less depression and
      stress, compared with the low acceptance subgroup. In what concerns self
      compassion, the low acceptance subgroup reported higher self-judgment, isolation
      and over identification, compared with the intermediate subgroup. These subgroups
      also differed from each other in common humanity and mindfulness. Implications
      and clinical utility of the results were discussed, suggesting the increase of
      willingness to pain as an important key in chronic pain interventions. 

PMID- 20806419
TI  - The relationship between resilience and levels of anxiety, depression, and
      obsessive-compulsive symptoms in adolescents.
AB  - OBJECTIVE: Mental health problems affect approximately 20% of adolescents.
      Traditionally, the principal focus has been on vulnerability and risk factors and
      less on protective factors. The study, therefore, explores the relation between
      frequent psychiatric symptoms and resilience factors among older adolescents.
      METHOD: The Resilience Scale for Adolescents (READ) was completed by 307
      Norwegian high school students (M = 16.4 years) along with the Depression Anxiety
      Stress Scales, and the Obsessive-Compulsive Inventory-Revised. RESULTS: Higher
      resilience scores predicted lower scores on levels of depression, anxiety, stress
      and obsessive-compulsive symptoms after controlling for age and gender.
      CONCLUSION: This study provides further evidence that it may be fruitful for
      clinicians and researchers to attend to resilience factors in relation to
      psychological symptoms among older adolescents.

PMID- 20806420
TI  - Factors associated with outcome of cognitive-behavioural therapy for complicated
      grief: a preliminary study.
AB  - Complicated grief (CG), also called prolonged grief disorder, is a debilitating
      condition that can develop following a loss. There is growing evidence that
      cognitive-behavioural interventions are efficacious in the treatment of CG. The
      present preliminary study used data from 43 patients with CG who were randomly
      assigned to cognitive-behavioural therapy in an earlier treatment trial to
      explore (a) predictors of outcome of cognitive-behavioural therapy for CG and (b)
      the relationship between symptom improvement and changes in loss-related negative
      cognitions and avoidance behaviours. Analyses showed that worse treatment outcome
      was associated with lower education attainment, loss of a partner/child (instead
      of some other relative), early treatment discontinuation, less patient motivation
      and more severe CG symptoms at pre-treatment. As predicted, stronger reduction in
      CG severity was significantly associated with stronger reductions in negative
      cognitions and avoidance. Implications of these findings are discussed.

PMID- 20806421
TI  - What is narrative therapy and what is it not?: the usefulness of Q methodology to
      explore accounts of White and Epston's (1990) approach to narrative therapy.
AB  - OBJECTIVE. 'What is narrative therapy and how do you do it?' is a question that
      is repeatedly asked of narrative therapy, with little consistent response. This
      study aimed to explore and distil out the 'common themes' of practitioner
      definitions of White and Epston's approach to narrative therapy. DESIGN. This was
      an Internet-based study involving current UK practitioners of this type of
      narrative therapy using a unique combination of a Delphi Panel and Q methodology.
      METHOD. A group of experienced practitioners were recruited into the Delphi Poll
      and were asked two questions about what narrative therapy is and is not, and what
      techniques are and are not employed. These data combined with other information
      formed the statements of a Q-sort that was then administered to a wider range of
      narrative practitioners. FINDINGS. The Delphi Panel agreed on a number of key
      points relating to the theory, politics and practice of narrative therapy. The Q
      sort produced eight distinct accounts of narrative therapy and a number of
      dimensions along which these different positions could be distinguished. These
      included narrative therapy as a political stance and integration with other
      approaches. CONCLUSIONS. For any therapeutic model to demonstrate its efficacy
      and attract proponents, an accepted definition of its components and practice
      should preferably be established. This study has provided some data for the UK
      application of White and Epston's narrative therapy, which may then assist in
      forming a firmer base for further research and practice.

PMID- 20806422
TI  - Preliminary validation of an ultra-brief version of the Penn State Worry
      Questionnaire.
AB  - The Penn State Worry Questionnaire (PSWQ) is widely regarded as the gold standard
      self-report questionnaire for pathological worry. However, the factorial
      structure of the scale remains contentious. We sought to determine whether a
      psychometrically sound brief version of the PSWQ, which avoids contentious items
      and yet incorporates the essential features of pathological worry, could be
      derived from the existing PSWQ item pool. After inspecting items of the PSWQ and
      the findings of previous factor analytic studies, three items were selected that
      capture the essence of pathological worry (i.e., high frequency, perceived
      uncontrollability and multiple domains of worry), according to the Diagnostic and
      Statistical Manual of Mental Disorders (Fourth Edition). We then compared the
      psychometric properties of the 3-item PSWQ with the full PSWQ in a sample of 225
      clients attending an anxiety disorders clinic. Despite its brevity, the 3-item
      PSWQ had internal consistency comparable with that of the standard PSWQ, and
      performed equally well with regards to convergent and discriminant validity, in
      screening for a generalized anxiety disorder diagnosis and in detecting change
      with treatment. The 3-item ultra-brief version of the PSWQ is quick to
      administer, simple to score and possesses psychometric properties very similar to
      the 16-item version. Further research should confirm the psychometric properties
      of the 3-item version when administered independently of the other items and
      assess the scale's test-retest reliability.

PMID- 20806423
TI  - Relationship between the Social Cognition and Object Relations Scale (SCORS) and
      attachment style in a clinical sample.
AB  - This present study examined the relationship between the Social Cognition and
      Object Relations Scale (SCORS) and two measures of adult attachment: the
      Relationship Questionnaire (RQ) and the Experiences in Close Relationships
      Questionnaire-Revised (ECR-R). Forty-five patients (76% female) at a university
      based outpatient treatment clinic participated in this study. We hypothesized
      that higher levels of attachment security would be associated with higher, more
      adaptive ratings on the SCORS variables. Results indicated that the SCORS Self
      Esteem (SE) variable was significantly positively related to the RQ's Secure
      Attachment ratings and negatively related with the ECR-R's Anxious Attachment
      scale. Additionally, negative trends were noted between SE and the RQ's Fearful
      and Preoccupied Attachment scores. The SCORS Emotional Investments in
      Relationships and Affective Quality of Representations variables were associated
      with higher Secure scores and lower, more maladaptive Preoccupied scores on the
      RQ. It was also associated with greater attachment anxiety as measured by the ECR
      R. Using both clinician (SCORS) and participant-rated measures (ECR-R and RQ),
      this study provides further understanding on how object representations and
      attachment style relate within a clinical sample. Results are discussed in light
      of prior research examining relationships between object relations and adult
      attachments, and clinical implications are also reviewed. Copyright (c) 2010 John
      Wiley & Sons, Ltd. Key Practitioner Message: * Individuals with higher levels of
      attachment anxiety may enter therapy with more self-image problems. * Individuals
      with higher levels of attachment anxiety may enter therapy with more maladaptive
      expectations about relationships. * Patients who endorse high levels of
      attachment anxiety (e.g., fearful and preoccupied) may be more likely to present
      with Axis II complaints. * Examining a patient's attachment style and object
      relations using different measures of assessment (e.g., explicit and implicit)
      can help gain a deeper and more comprehensive understanding of a patient.

PMID- 20806424
TI  - The monetary value of a life year: evidence from a qualitative study of treatment
      costs.
AB  - A small number of studies have provided suggestive evidence that the general
      public rejects the idea of giving higher priority to low-cost patients, in the
      context of a limited budget, in order to maximise health benefits. The study
      reported here used semi-structured group discussions to investigate the normative
      bases of such views among the Australian public. Discussion groups help
      participants reflect critically upon their own reasoning processes and go some
      way towards revealing underlying values rather than unreflective preferences. As
      a part of the exercise, participants were asked to allocate a hospital budget.
      After discussion and deliberation only three out of 41 chose to allocate all of
      the money to the low-cost patients. Reasons were not based on conceptual
      confusion or lack of insight into the implications of the different strategies,
      but rather on views about fairness, including the importance of giving all groups
      a 'chance' of being treated and of not removing 'hope' from high-cost patients.
      The results suggest that as costs rise people are willing to pay more than the
      minimum cost of a quality-adjusted life year for equity reasons, indicating that
      caution must be exercised in estimating a single monetary value for a QALY.

PMID- 20806425
TI  - Critical design criteria for minimal antibiotic-free plasmid vectors necessary to
      combine robust RNA Pol II and Pol III-mediated eukaryotic expression with high
      bacterial production yields.
AB  - BACKGROUND: For safety considerations, regulatory agencies recommend the
      elimination of antibiotic resistance markers and non-essential sequences from
      plasmid DNA-based gene medicines. In the present study, we analyzed antibiotic
      free (AF) vector design criteria impacting upon bacterial production and
      mammalian transgene expression. METHODS: Both CMV-HTLV-I R RNA Pol II promoter
      (protein transgene) and murine U6 RNA Pol III promoter (RNA transgene) vector
      designs were studied. Plasmid production yield was assessed through inducible fed
      batch fermentation. RNA Pol II-directed enhanced green fluorescent protein and
      RNA Pol III-directed RNA expression were quantified by fluorometry and
      quantitative real-time polymerase chain reaction, respectively, after
      transfection of human HEK293 cells. RESULTS: Sucrose-selectable minimalized
      protein and therapeutic RNA expression vector designs that combined an RNA-based
      AF selection with highly productive fermentation manufacturing (>1000 mg/l
      plasmid DNA) and high-level in vivo expression of encoded products were
      identified. The AF selectable marker was also successfully applied to convert
      existing kanamycin-resistant DNA vaccine plasmids gWIZ and pVAX1 into AF vectors,
      demonstrating a general utility for retrofitting existing vectors. A minimum
      vector size for high yield plasmid fermentation was identified. A strategy for
      stable fermentation of plasmid dimers with improved vector potency and
      fermentation yields up to 1740 mg/l was developed. CONCLUSIONS: We report the
      development of potent high yield AF gene medicine expression vectors for protein
      or RNA (e.g. short hairpin RNA or microRNA) products. These AF expression vectors
      were optimized to exceed a newly-identified size threshold for high copy plasmid
      replication and direct higher transgene expression levels than alternative
      vectors.

PMID- 20806426
TI  - Delayed assessment and eager adoption of laparoscopic cholecystectomy:
      implications for developing surgical technologies.
AB  - Despite the prevailing emphasis in the medical literature on establishing
      evidence, many changes in the practice of surgery have not been achieved using
      proper evidence-based assessment. This paper examines the adoption of
      laparoscopic cholecystectomy (LC) into regular use for the treatment of
      cholecystitis and the process of its acceptance, focusing on the limited role of
      technology assessment in its appraisal. A review of the published medical
      literature concerning LC was performed. Approximately 3000 studies of LC have
      been conducted since 1985, and there have been nearly 8500 publications to date.
      As LC was adopted enthusiastically into practice, the results of outcome studies
      generally showed that it compared favorably with the traditional, open
      cholecystectomy with regard to mortality, complications, and length of hospital
      stay. However, despite the rapid general agreement on surgical technique,
      efficacy, and appropriateness, there remained lingering doubts about safety,
      outcomes, and cost of the procedure that suggested that essential research
      questions were ignored even as the procedure became standard. Using LC as a case
      study, there are important lessons to be learned about the need for important
      guidelines for surgical innovation and the adoption of minimally invasive
      surgical techniques into current clinical and surgical practice. We highlight one
      recent example, natural orifice transluminal endoscopic surgery and how necessary
      it is to properly evaluate this new technology before it is accepted as a safe
      and effective surgical option.

PMID- 20806427
TI  - Treatment of liver hydatidosis: how to treat an asymptomatic carrier?
AB  - Liver hydatidosis is the most common clinical presentation of cystic
      echinococcosis (CE). Ultrasonographic mass surveys have demonstrated the true
      prevalence, including the asymptomatic characteristic of the majority of cases,
      providing new insight into the natural history of the disease. This raises the
      question of whether to treat or not to treat these patients, due to the high and
      unsuspected prevalence of CE. The high rate of liver/lung frequencies of cyst
      localization, the autopsy findings, and the involution of cysts demonstrated in
      long time follow-up of asymptomatic carriers contribute to this discussion. The
      decision to treat an asymptomatic patient by surgery, albendazole, or puncture
      aspiration injection and re-aspiration or to wait and watch, is based on
      conflicting reports in the literature, the lack of complications in untreated
      patients over time, and the spontaneous disappearance and involution of cysts.
      All these points contribute to difficulties of individual clinical decisions. The
      patients should be informed of the reasons and the risks of watchful/waiting
      without treatment, the possibility of complications, and the risks of the other
      options. As more information on the natural history of liver hydatidosis is
      acquired, selection of the best treatment will be come easier. Without this
      knowledge it would be very difficult to establish definitive rules of treatment.
      At present, it is possible to manage these patients over time and to wait for the
      best moment for treatment. Follow-up studies must be conducted to achieve this
      objective.

PMID- 20806428
TI  - Epstein-Barr virus: silent companion or causative agent of chronic liver disease?
AB  - The Epstein-Barr virus (EBV) has an important and multifaceted role in liver
      pathology. As a member of the herpes virus family, EBV establishes a persistent
      infection in more than 90% of adults. Besides acute hepatitis during primary
      infection, many clinical syndromes of interest for the hepatologist are
      associated with EBV infection. The role of EBV in the evolution of chronic
      hepatitis from hepatotropic viruses is considered. Chronic EBV-associated
      hepatitis is suspected in immunocompetent adults with compatible serology,
      suggestive histology and detection of the viral genome in the liver and/or
      increase of specific circulating cytotoxic T-lymphocytes. EBV is the main cause
      of post-transplant lymphoproliferative disorders which occur in up to 30% of
      cases. EBV-driven lymphoproliferative diseases are also recognized in non
      immunocompromised patients and liver is involved in up to a third of the cases.
      Directly implicated in the pathogenesis of different tumors, EBV has a disputable
      role in hepatocellular carcinoma carcinogenesis. Further research is required in
      order to establish or reject the role of EBV in human liver cancer. This paper
      attempts to discuss the range of EBV-associated chronic liver diseases in
      immunocompetent patients, from mild, self-limiting mononuclear hepatitis to liver
      cancer.

PMID- 20806429
TI  - Design of 16S rRNA gene primers for 454 pyrosequencing of the human foregut
      microbiome.
AB  - AIM: To design and validate broad-range 16S rRNA primers for use in high
      throughput sequencing to classify bacteria isolated from the human foregut
      microbiome. METHODS: A foregut microbiome dataset was constructed using 16S rRNA
      gene sequences obtained from oral, esophageal, and gastric microbiomes produced
      by Sanger sequencing in previous studies represented by 219 bacterial species.
      Candidate primers evaluated were from the European rRNA database. To assess the
      effect of sequence length on accuracy of classification, 16S rRNA genes of
      various lengths were created by trimming the full length sequences. Sequences
      spanning various hypervariable regions were selected to simulate the amplicons
      that would be obtained using possible primer pairs. The sequences were compared
      with full length 16S rRNA genes for accuracy in taxonomic classification using
      online software at the Ribosomal Database Project (RDP). The universality of the
      primer set was evaluated using the RDP 16S rRNA database which is comprised of
      433 306 16S rRNA genes, represented by 36 phyla. RESULTS: Truncation to 100
      nucleotides (nt) downstream from the position corresponding to base 28 in the
      Escherichia coli 16S rRNA gene caused misclassification of 87 (39.7%) of the 219
      sequences, compared with misclassification of only 29 (13.2%) sequences with
      truncation to 350 nt. Among 350-nt sequence reads within various regions of the
      16S rRNA gene, the reverse read of an amplicon generated using the 343F/798R
      primers had the least (8.2%) effect on classification. In comparison, truncation
      to 900 nt mimicking single pass Sanger reads misclassified 5.0% of the 219
      sequences. The 343F/798R amplicon accurately assigned 91.8% of the 219 sequences
      at the species level. Weighted by abundance of the species in the esophageal
      dataset, the 343F/798R amplicon yielded similar classification accuracy without a
      significant loss in species coverage (92%). Modification of the 343F/798R primers
      to 347F/803R increased their universality among foregut species. Assuming that a
      typical polymerase chain reaction can tolerate 2 mismatches between a primer and
      a template, the modified 347F and 803R primers should be able to anneal 98% and
      99.6% of all 16S rRNA genes in the RDP database. CONCLUSION: 347F/803R is the
      most suitable pair of primers for classification of foregut 16S rRNA genes but
      also possess universality suitable for analyses of other complex microbiomes.

PMID- 20806430
TI  - Effect of probiotics on pro-inflammatory cytokines and NF-kappaB activation in
      ulcerative colitis.
AB  - AIM: To demonstrate the therapeutic effect of probiotics in patients with
      ulcerative colitis (UC), and their effect on inflammatory mediators and nuclear
      factor (NF)-kappaB activation in these patients. METHODS: Thirty patients with
      mild to moderate UC were randomly classified into two groups: sulfasalazine
      group, who received sulfasalazine 2400 mg/d; and probiotic group, who received
      sulfasalazine 2400 mg/d with probiotic. The patients were investigated before and
      after 8 wk of treatment with probiotic (Lactobacillus delbruekii and
      Lactobacillus fermentum). Colonic activity of myeloperoxidase (MPO) was assayed
      with UV spectrophotometry, the colonic content of interleukin (IL)-6 was
      determined by enzyme-linked immunosorbent assay (ELISA), fecal calprotectin was
      determined by ELISA, and expression of NF-kappaB p65 and tumor necrosis factor
      (TNF)-alpha proteins in colonic tissue was identified by immunohistochemistry and
      reverse transcription polymerase chain reaction, respectively. RESULTS: At the
      start of the study, colonic mucosal injury and inflammation were demonstrated in
      UC patients by hematoxylin and eosin staining, and an increase in colonic MPO
      activity, fecal calprotectin, and expression of colonic TNF-alpha and NF-kappaB
      p65 proteins. The use of probiotic for 8 wk significantly ameliorated the
      inflammation by decreasing the colonic concentration of IL-6, expression of TNF
      alpha and NF-kappaB p65, leukocyte recruitment, as demonstrated by a decrease in
      colonic MPO activity, and the level of fecal calprotectin compared to
      sulfasalazine group and the control group (P < 0.05). CONCLUSION: Oral
      supplementation with probiotics could be helpful in maintaining remission and
      preventing relapse of UC.

PMID- 20806432
TI  - ESWL for difficult bile duct stones: a 15-year single centre experience.
AB  - AIM: To evaluate the efficacy of extracorporeal shock wave lithotripsy (ESWL) for
      the management of refractory bile duct cholelithiasis in a third level referral
      centre. METHODS: The clinical records of all patients treated with a second
      generation electromagnetic lithotripter (Lithostar Plus, SIEMENS) from October
      1990 to April 2005 were evaluated. All patients were monitored during the
      procedure and antibiotics were administered in case of cholangitis. The chi(2)
      test and logistic regression analysis were performed as appropriate. RESULTS: Two
      hundred and fourteen patients (102 males, 112 females; mean age 74.8 +/- 0.84
      years--single stone 97, multiple stones 117) underwent ESWL. The mean number of
      sessions and shock waves were 3.5 +/- 0.13 and 3477.06 +/- 66.17, respectively.
      The maximum stone size was 5 cm. Complete stone clearance was achieved in 192
      (89.7%) patients. Of the remaining patients 15 required surgery, 2 a palliative
      stent and in 5 patients stone fragmentation led to effective bile drainage with
      clinical resolution despite incomplete clearance. Age, sex and stone
      characteristics were not related to treatment outcome. Major complications
      occurred in two patients (haemobilia and rectal bleeding) and minor complications
      in 25 (3 vomiting, 22 arrhythmias). No procedure-related deaths occurred.
      CONCLUSION: ESWL is a safe and effective technique for clearance of refractory
      bile duct stones.

PMID- 20806431
TI  - Chemoprotective effects of curcumin in esophageal epithelial cells exposed to
      bile acids.
AB  - AIM: To investigate the ability of curcumin to counteract the impact of bile
      acids on gene expression of esophageal epithelial cells. METHODS: An esophageal
      epithelial cell line (HET-1A) was treated with curcumin in the presence of
      deoxycholic acid. Cell proliferation and viability assays were used to establish
      an appropriate dose range for curcumin. The combined and individual effects of
      curcumin and bile acid on cyclooxygenase-2 (COX-2) and superoxide dismutase (SOD
      1 and SOD-2) gene expression were also assessed. RESULTS: Curcumin in a dose
      range of 10-100 micromol/L displayed minimal inhibition of HET-1A cell viability.
      Deoxycholic acid at a concentration of 200 micromol/L caused a 2.4-fold increase
      in COX-2 gene expression compared to vehicle control. The increased expression of
      COX-2 induced by deoxycholic acid was partially reversed by the addition of
      curcumin, and curcumin reduced COX-2 expression 3.3- to 1.3-fold. HET-1A cells
      exposed to bile acid yielded reduced expression of SOD-1 and SOD-2 genes with the
      exception that high dose deoxycholic acid at 200 mumol/L led to a 3-fold increase
      in SOD-2 expression. The addition of curcumin treatment partially reversed the
      bile acid-induced reduction in SOD-1 expression at all concentrations of curcumin
      tested. CONCLUSION: Curcumin reverses bile acid suppression of gene expression of
      SOD-1. Curcumin is also able to inhibit bile acid induction of COX-2 gene
      expression.

PMID- 20806433
TI  - Outcome of surgical treatment of intestinal perforation in typhoid fever.
AB  - AIM: To represent our clinical experience in the treatment of intestinal
      perforation arising from typhoid fever. METHODS: The records of 22 surgically
      treated patients with typhoid intestinal perforation were evaluated
      retrospectively. RESULTS: There were 18 males and 4 females, mean age 37 years
      (range, 8-64 years). Presenting symptoms were fever, abdominal pain, diarrhea or
      constipation. Sixteen cases were subjected to segmental resection and end-to-end
      anastomosis, while 3 cases received 2-layered primary repair following
      debridement, one case with multiple perforations received 2-layered primary
      repair and end ileostomy, one case received segmental resection and end-to-end
      anastomosis followed by an end ileostomy, and one case received segmental
      resection and end ileostomy with mucous fistula operation. Postoperative
      morbidity was seen in 5 cases and mortality was found in one case. CONCLUSION:
      Intestinal perforation resulting from Salmonella typhi is an important health
      problem in Eastern and Southeastern Turkey. In management of this illness, early
      and appropriate surgical intervention is vital.

PMID- 20806434
TI  - Non-alcoholic steatohepatitis and influence of age and gender on histopathologic
      findings.
AB  - AIM: To characterize the histopathologic specifications of non-alcoholic
      steatohepatitis (NASH) according to age and gender. METHODS: An analytical cross
      sectional study was conducted in two private gastroenterology clinics on biopsy
      proven patients suffering from NASH. Biopsy histopathologic findings as well as
      demographic and laboratory data of the patients at the time of biopsy were
      gathered retrospectively from clinical records. The grading and staging of
      histopathologic findings were performed according to the Brunt method after
      reevaluation of the slides by a pathologist. Patients were divided into two
      groups according to age (below and above 55 years). Mean quantitative grade of
      all pathologic findings were also calculated according to Brunt scoring values.
      RESULTS: A total number of 77 NASH patients, consisting of 58 males (75.3%) and
      19 (24.7%) females with a mean age of 41.99 +/- 11.80 years (range, 18-70 years),
      were enrolled. The mean age (48.72 +/- 13.99 years vs 39.74 +/- 10.16 years, P =
      0.004) and aspartate aminotransferase level (75.11 +/- 29.68 U/L vs 52.78 +/-
      25.00 U/L, P = 0.002) was significantly higher in female patients. Mean
      quantitative grade of hepatosteatosis was significantly higher in females (2.00
      +/- 0.82 vs 1.59 +/- 0.68, P = 0.031) compared to males. Fifty four percent
      (34/65) of young patients had mild hepatosteatosis (Grade I) while only one
      patient (11.2%) in the older group had grade I hepatosteatosis. Patients aged >
      or = 55 had significantly more severe hepatosteatosis (Grade III) (44.4% vs 9.5%,
      P = 0.007) and the mean quantitative grade of hepatosteatosis was significantly
      higher among them (2.33 +/- 0.71 vs 1.56 +/- 0.67, P = 0.002). Multivariate
      analysis after omitting the confounding role of age revealed a higher grade of
      hepatosteatosis in female patients (P = 0.010). CONCLUSION: These findings point
      toward the possible influence of age in the severity of steatohepatitis, portal
      and lobar inflammation in patients suffering from NASH while gender independently
      might contribute to the level of steatohepatitis.

PMID- 20806435
TI  - Age-dependent eradication of Helicobacter pylori in Japanese patients.
AB  - AIM: To determine the general risk factors affecting the failure rate of first
      line eradication therapy in Japanese patients with Helicobacter pylori (H.
      pylori) infection. METHODS: The present study enrolled 253 patients who had an H.
      pylori infection, underwent gastro-endoscopy, and were treated with H. pylori
      eradication therapy. Eradication therapy consisted of 30 mg lansoprazole plus 750
      mg amoxicillin and 400 mg clarithromycin twice daily for 7 d. All of the patients
      underwent a 13C urea breath test at least 1 mo after the completion of
      eradication therapy. The current study investigated the independent factors
      associated with successful H. pylori eradication using a multiple logistic
      regression analysis. RESULTS: The overall success rate in the patients was 85.8%.
      Among the general factors examined in the multivariate analyses, only having an
      age less than 50 years was found to be significantly associated with a poor
      response to H. pylori eradication. Moreover, side effects were the only clinical
      factors in the patients who were under 50 years of age that significantly
      influenced the poor response to H. pylori eradication. CONCLUSION: H. pylori
      positive elderly patients should undergo eradication therapy. In addition, it is
      necessary to improve H. pylori eradication therapy in younger patients.

PMID- 20806436
TI  - Efficient hemostatic method for endoscopic submucosal dissection of colorectal
      tumors.
AB  - AIM: To evaluate a new hemostatic method using hemostatic forceps to prevent
      perforation and perioperative hemorrhage during colonic endoscopic submucosal
      dissection (ESD). METHODS: We studied 250 cases, in which ESD for colorectal
      tumors was performed at the Kyoto Prefectural University of Medicine or Nara City
      Hospital between 2005 and 2010. We developed a new hemostatic method using
      hemostatic forceps in December 2008 for the efficient treatment of submucosal
      thick vessels. ESD was performed on 126 cases after adoption of the new method
      (the adopted group) and the new method was performed on 102 of these cases. ESD
      was performed on 124 cases before the adoption of the new method (the unadopted
      group). The details of the new method are as follows: firstly, a vessel was
      coagulated using the hemostatic forceps in the soft coagulation mode according to
      the standard procedure, and the coagulated vessel was removed using the forceps
      in the "endocut" mode without perioperative hemorrhage. Secondly, the partial
      surrounding submucosa was dissected using the forceps in the endocut mode. In the
      current study, we evaluated the efficacy of this method. RESULTS: Coagulated
      vessels were successfully removed using the hemostatic forceps in all 102 cases
      without severe perioperative hemorrhage. Moderate perioperative hemorrhage
      occurred in five cases (4.9%); however, it was stopped by immediately reuse of
      the hemostatic forceps. The partial surrounding submucosa was dissected using the
      forceps in all 102 cases. In the adopted group, the median operation time was 105
      min. The proportion of endoscopic en bloc resection was 92.8% (P < 0.01) compared
      to 80.6% in the unadopted group. The postoperative hemorrhage and perforation
      rates were 2.3% and 2.3%. The rate of perforation was significantly lower than
      that in the unadopted group (9.6%, P < 0.01). We evaluated the ease of use of
      this method by allowing our three trainees to performed ESD on 46 cases, which
      were accomplished without any severe hemorrhage. CONCLUSION: The new method
      effectively treated submucosal thick vessels and shows promise for the prevention
      of perforation and perioperative hemorrhage in colonic ESD.

PMID- 20806437
TI  - Diagnostic sensitivity of imaging modalities for hepatocellular carcinoma smaller
      than 2 cm.
AB  - AIM: To compare the imaging results with histology and to evaluate the diagnostic
      sensitivity of imaging modalities for hepatocellular carcinoma (HCC) smaller than
      2 cm. METHODS: Nodules smaller than 2 cm (n = 34) revealed by ultrasonography
      (US) in 29 patients with liver cirrhosis were analyzed. Histological diagnosis of
      HCC was performed by ultrasonographic guidance: moderately-differentiated HCC (n
      = 24); well-differentiated HCC (n = 10). The patterns disclosed by the four
      imaging modalities defined the conclusive diagnosis of HCC: (1) contrast-enhanced
      computed tomography (CECT), hypervascularity in the arterial phase and washout in
      the equilibrium phase; (2) Sonazoid contrast-enhanced US (CEUS), hypervascularity
      in the early vascular phase and defect in the Kupffer phase; (3) gadolinium
      ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic
      resonance imaging (MRI), hypervascularity in the arterial phase and/or defect in
      the hepatobiliary phase; and (4) CT arterioportal angiography: hypervascularity
      by CT during arteriography and/or perfusion defect by CT during arterial
      portography. RESULTS: Overall, the sensitivity of diagnosing HCC smaller than 2
      cm was 52.9% (18/34) (95% CI: 35.1-70.2) by CECT; 67.6% (23/34) (95% CI: 49.5
      82.6) by Sonazoid CEUS; 76.5% (26/34) (95% CI: 58.8-89.3) by Gd-EOB-DTPA MRI; and
      88.2% (30/34) (95% CI: 72.5-96.7) by CT arterioportal angiography. The diagnostic
      sensitivity of detecting moderately-differentiated HCC by CECT, Sonazoid CEUS, Gd
      EOB-DTPA MRI and CT arterioportal angiography was 62.5% (15/24) (95% CI: 40.6
      81.2), 79.2% (19/24) (95% CI: 57.8-92.9), 75.0% (18/24) (95% CI: 53.3-90.2) and
      95.8% (23/24) (95% CI: 78.9-99.9), respectively. A significant difference (P <
      0.05) was observed between CECT and CT arterioportal angiography in all nodules.
      There was no difference between Sonazoid CEUS, Gd-EOB-DTPA MRI, and CT
      arterioportal angiography. The combined sensitivity of Sonazoid CEUS and Gd-EOB
      DTPA MRI was 94.1% (32/34). CONCLUSION: Changing the main diagnostic modality for
      HCC smaller than 2 cm from CT arterioportal angiography to Sonazoid CEUS and Gd
      EOB-DTPA MRI is recommended.

PMID- 20806438
TI  - Effect of Arctium lappa L. in the dextran sulfate sodium colitis mouse model.
AB  - AIM: To analyze the possible protective role of Arctium lappa L. (AL) in a murine
      model of ulcerative colitis (UC). METHODS: BALB/c mice were administered 100
      mg/kg AL powder orally each day. After 7 d, colitis was induced by administration
      of dextran sulfate sodium (DSS) (5% W/V) in drinking water for a further 8
      consecutive days. Diarrhea and bloody stools as well as colonic histology were
      observed. The level of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF
      alpha) in colonic sections were detected by immunohistochemistry. RESULTS: There
      were significant differences in mean body weight values and disease activity
      indices between controls and AL-treated animals. Moreover, the histological
      findings showed that AL treatment can prevent mucosal edema, submucosal erosions,
      ulceration, inflammatory cell infiltration and colon damage. In addition,
      immunohistochemistry analysis showed that the levels of the inflammatory
      cytokines, IL-6 and TNF-alpha were also decreased in AL-treated groups.
      CONCLUSION: We suggest that AL can prevent intestinal damage and decrease
      inflammatory cytokines in mice with DSS-induced colitis. Thus, AL could prove to
      be a useful food for UC.

PMID- 20806439
TI  - Conservative management of chronic gastric volvulus: 44 cases over 5 years.
AB  - AIM: To investigate clinical outcomes of patients with chronic gastric volvulus
      (GV) who were managed conservatively over a 5-year period. METHODS: A total of 44
      consecutive patients with chronic GV, as diagnosed by barium study between
      October 2002 and July 2008 were investigated. All of these patients received
      conservative management initially without anatomical correction. Their clinical
      manifestations, diagnostic work-ups, and clinical outcomes were analyzed. We
      sought to identify independent risk factors for poor outcome by using the Cox
      proportional hazards model. RESULTS: The enrolled patients were predominantly
      male (n = 37, 84%) and of advanced age (median: 71 years old, interquartile
      range: 57.5-78 years). Abdominal pain and fullness were the most common
      presentations. During the follow-up period (median: 16 mo, up to 69 mo), there
      was no severe complication, but symptomatic recurrence was noted in 28 patients
      (64%). Only one patient turned to elective surgery for frequent symptoms.
      Peritoneal adhesion was the only independent risk factor associated with
      recurrence (hazard ratio: 2.58, 95% CI: 1.08-6.13, P = 0.033). CONCLUSION:
      Symptomatic recurrence of chronic GV is very common although serious
      complications infrequently occur with conservative management. Peritoneal
      adhesion is independently associated with recurrence.

PMID- 20806440
TI  - A newly designed big cup nitinol stent for gastric outlet obstruction.
AB  - AIM: To find out whether a newly designed big cup nitinol stent is suitable for
      treatment of patients with gastric outlet obstruction resulting from gastric
      cancer. METHODS: The new stent is composed of a proximal big cup segment (20 mm
      in length and 48-55 mm in diameter), a middle part (60 mm in length and 20 mm in
      diameter) covered by a polyethylene membrane and a distal sphericity (20 mm in
      length and 28 mm in diameter). Half of the proximal big cup segment is also
      covered by a polyethylene membrane, which is adjacent to the middle part of the
      stent. The stent is preloaded in a 6.0-mm-diameter introducer system. Thirteen
      patients with gastric outlet obstruction resulting from gastric cancer received
      the new stents under endoscopic and fluoroscopic guidance. RESULTS: Technical
      success was achieved in 12 of 13 (92.3%) patients. Among the 12 patients in whom
      endoscopic stent was placed successfully, the clinical success rate was 91.7%
      during a follow-up of average 6.5 mo. During the first month follow-up, the
      migration rate was 0%, recurrent obstruction 0% and gastric bleeding 8.3%. During
      the follow-up between 2-12 mo, no migration, recurrent obstruction and gastric
      bleeding occurred. CONCLUSION: The proximal big cup segment seems to be effective
      and promising for technical efficacy, clinical outcome, and preventing migration
      and tumor ingrowth and increasing the emptying rate of sinus ventriculi.

PMID- 20806441
TI  - Relationship between genetic polymorphisms of ALDH2 and ADH1B and esophageal
      cancer risk: a meta-analysis.
AB  - AIM: To evaluate the contribution of alcohol dehydrogenase-1B (ADH1B) and
      aldehyde dehydrogenase-2 (ALDH2) polymorphisms to the risk of esophageal cancer.
      METHODS: Nineteen articles were included by searching MEDLINE, EMBASE and the
      Chinese Biomedical Database, 13 on ADH1B and 18 on ALDH2. We performed a meta
      analysis of case-control studies including 13 studies on ADH1B (cases/controls:
      2390/7100) and 18 studies on ALDH2 (2631/6030). RESULTS: The crude odds ratio [OR
      (95% confidence interval)] was 2.91 (2.04-4.14) for ADH1B*1/*1 (vs ADH1B*2/*2)
      and 1.32 (1.17-1.49) for ADH1B*1/*2. The crude OR for ALDH2*1/*2 (vs ALDH2*1/*1)
      was 2.52 (1.76-3.61). ADH1B*1/*1 increased the risk of esophageal cancer among
      never/rare [1.56 (0.93-2.61)], moderate [2.71 (1.37-5.35)], and heavy drinkers
      [3.22 (2.27-4.57)]. ADH1B*1/*2 was associated with a modest risk among moderate
      drinkers [1.43 (1.09-1.87)]. ALDH2*1/*2 increased the risk among never/rare [1.28
      (0.91-1.80)], moderate [3.12 (1.95-5.01)], and heavy [7.12 (4.67-10.86)]
      drinkers, and among ex-drinkers [5.64 (1.57-20.25)]. ALDH2*2/*2 increased the
      risk among drinkers [4.42 (1.72-11.36)]. ADH1B*1/*1 plus ALDH2*1/*2 was
      associated with the highest risk for heavy drinkers [12.45 (2.9-53.46)]. The
      results of the meta-regression analysis showed that the effects of ADH1B*1/*1 and
      ALDH2*1/*2 increased with the level of alcohol consumption. ALDH2*1/*2 was
      associated with a high risk among Taiwan Chinese and Japanese drinkers, as
      opposed to a moderate risk among drinkers in high-incidence regions of Mainland
      China. ADH1B*1/*1 in heavy drinkers and ALDH2*1/*2 in moderate-to-heavy drinkers
      was associated with similarly high risk among both men and women. CONCLUSION:
      ADH1B/ALDH2 genotypes affect the risk of esophageal cancer, and the risk is
      modified by alcohol consumption, ethnicity, and gender.

PMID- 20806442
TI  - Prevalence of irritable bowel syndrome in Chinese college and university students
      assessed using Rome III criteria.
AB  - AIM: To estimate the prevalence of irritable bowel syndrome (IBS) in college and
      university students of North China and certain related factors for IBS. METHODS:
      A total of 2500 students from Shandong University in North China were asked in
      February-March 2009 to complete questionnaires, including the Rome III
      questionnaire, hospital anxiety and depression scale, and IBS-quality of life
      questionnaire (IBS-QOL). RESULTS: Among the 2126 students with complete data, the
      prevalence of IBS was 7.85% according to the Rome III criteria, with a
      female/male ratio of 1.78:1. Most students had the IBS-constipation subtype
      (36.5%), followed by IBS-diarrhea subtype (31.1%) and IBS-mixed subtype (23.9%).
      The students with IBS had a higher anxiety and depression score than those
      without IBS. Low exercise level and anxiety indicated a high risk for IBS. The
      mean score of IBS patients was 74.2 +/- 4.242 on the IBS-QOL. CONCLUSION: The
      prevalence of IBS is 7.85% in Chinese college and university students according
      to the Rome III criteria. Low exercise level and anxiety may be the risk factors
      for IBS.

PMID- 20806443
TI  - Efficacy evaluation of imatinib treatment in patients with gastrointestinal
      stromal tumors: a meta-analysis.
AB  - AIM: To perform a meta-analysis to derive a more precise estimation of imatinib
      treatment for different genotypes of gastrointestinal stromal tumors (GIST).
      METHODS: Studies were identified by searching PubMed and Embase. Inclusive
      criteria were patients with exon 9-mutant, exon 11-mutant or wide type (WT) GIST,
      receiving chemotherapy of imatinib for clinical trial, and efficacy evaluation
      was cumulative response (CR) including complete response and partial response.
      The odds ratios (OR) for CR in stem cell factor receptor (KIT) mutation patients
      vs WT genotype patients, KIT exon 11-mutant genotype patients vs KIT exon 9
      mutant genotype patients and KIT exon 9-mutant genotype patients vs WT genotype
      patients were calculated with 95% confidence interval (CI) for each study as an
      estimation of the efficacy of imatinib. RESULTS: Five studies including 927
      patients were involved in this meta-analysis. The overall OR (KIT group vs WT
      group) was 3.34 (95% CI: 2.30-4.86, P < 0.00001, P(heterogeneity) = 0.04). The
      overall OR in KIT exon 11 group vs KIT exon 9 group was 3.29 (95% CI: 2.17-5.00,
      P < 0.00001, P(heterogeneity) = 0.33). The overall OR in KIT exon 9 group vs WT
      group was 1.23 (95% CI: 0.73-2.10, P = 0.44, P(heterogeneity) = 0.42).
      CONCLUSION: Most patients with different genotypes of GIST and KIT exon 11-mutant
      will benefit from the individualized treatment of imatinib.

PMID- 20806444
TI  - Agressive inflammatory myofibroblastic tumor of the liver with underlying
      schistosomiasis: a case report.
AB  - Inflammatory myofibroblastic tumor (IMT) occurs infrequently in the liver. It is
      controversial whether it represents a low grade mesenchymal neoplasm or a
      reactive inflammatory lesion. Local recurrence and metastasis are rare and some
      tumors are associated with infectious agents. We report on a case of a large and
      partially resected IMT with local recurrence and diaphragm and kidney
      infiltration detected on routine surveillance two years later. Histologically,
      the tumor showed spindle cells without atypia, mitosis or necrotic areas in a
      myxoid and collagenized background with inflammatory cells. In the liver portal
      tracts, granulomatous lesions with viable eggs of Schistosoma mansoni were
      identified. Immunohistochemistry demonstrated spindle cells which were smooth
      muscle actin and vimentin positive. In conclusion, this case points out that
      these histological patterns do not predict the aggressive biological behavior of
      the lesion. A reason for the recurrence and the infiltration may be incomplete
      tumor resection. Further investigation is necessary in order to better clarify an
      infectious cause in some IMTs.

PMID- 20806454
TI  - Biology and Pathogenecity of Free-Living Amoebae. Proceedings from the XIIIth
      International Meeting on the Biology and Pathogenicity of Free-Living Amoebae,
      FLAM 2009, Tenerife, Spain.

PMID- 20806445
TI  - Multi-site abdominal tuberculosis mimics malignancy on 18F-FDG PET/CT: report of
      three cases.
AB  - 18F-fluorodeoxyglucose positron emission/computed tomography (18F-FDG PET/CT)
      imaging, an established procedure for evaluation of malignancy, shows an
      increased 18F-FDG uptake in inflammatory conditions. We present three patients
      with abdominal pain and weight loss. Conventional imaging studies indicated that
      abdominal neoplasm and 18F-FDG PET/CT for assessment of malignancy showed
      multiple lesions with intense 18F-FDG uptake in abdomen of the three cases.
      However, the three patients were finally diagnosed with multi-site abdominal
      tuberculosis (TB). Of them, two were diagnosed with TB by pathology, one was
      diagnosed with TB clinically. They recovered after anti-TB therapy. Few reports
      on accumulation of 18F-FDG in abdominal TB are available in the literature. A
      high index of suspicion is necessary to achieve an early diagnosis and a better
      outcome of the disease.

PMID- 20806455
TI  - Proceedings of the 5th Copenhagen Workshop on Endocrine Disrupters: Ubiquitous
      endocrine disrupters and possible human health effects, 20-22 May 2009.

PMID- 20806456
TI  - Proceedings of the Summit on Systems Biology 2009: The Microbial World and
      Beyond, June 16- 19, 2009, Richmond, Virginia, USA.

PMID- 20806457
TI  - Interventional cardiology: Promising improvements in DES technology.

PMID- 20806459
TI  - Lead aVR in STEMI diagnosis.

PMID- 20806458
TI  - Stent fracture in the coronary and peripheral arteries.
AB  - Inherent risks of stenting include restenosis and thrombosis. Recently, stent
      fractures have been recognized as a complication that may result in thrombosis,
      perforation, restenosis, and migration of the stent resulting in morbidity and
      mortality. Stent fractures were originally seen in the superficial femoral
      arteries but have since then been reported in almost all vascular sites including
      the coronary, renal, carotid, iliac, and femoropopliteal arteries. Fractures are
      the result of the complex interplay between stent manufacturing, the stented
      segment, pulsatile and nonpulsatile biomechanical forces, and plaque morphology
      at a particular vascular site. The presentation of a patient with a fracture is
      highly variable, ranging from asymptomatic in nature, detected on routine
      screening without any sequelae, to sudden cardiac death related to a thrombosed
      coronary artery. Despite being recognized as an important complication, consensus
      on routine surveillance and diagnostic methods to detect fractures continues to
      be lacking. Fortunately, most cases are relatively benign and can be managed
      conservatively if detected. In the setting of recurrent symptoms, further
      intervention is usually sought. In review of the literature most cases are
      managed with placement of a stent over the fractured area, the stent-in-stent
      technique, but several other alternatives may be available. As the knowledge of
      the variables that make stents prone to fracture are identified, better
      technologies and techniques can be employed to minimize the risk of this
      complication. This article reviews the available literature on stent fractures
      and complications using data found on PubMed, MEDLINE, the Manufacturer and User
      Facility Device Experience (MAUDE) database, and the Cochrane databases.

PMID- 20806460
TI  - Coronary artery disease: Fractional flow reserve successfully predicts ischemic
      stenoses.

PMID- 20806461
TI  - Risk factors: Eating for two? Maternal weight gain and offspring cardiovascular
      risk.

PMID- 20806462
TI  - Population trends in MI explored.

PMID- 20806463
TI  - Prevention:  Group medical clinics to manage diabetes and hypertension.

PMID- 20806464
TI  - Antiplatelet therapy: Long-term dual antiplatelet therapy and bleeding in stable
      patients--insights from CHARISMA.

PMID- 20806465
TI  - Festschrift in honor of Martin C. Mihm, Jr, MD.

PMID- 20806467
TI  - Proceedings from the Third Congress of the International Society of
      Nutrigenetics/Nutrigenomics (ISNN), October 21-23, 2009, Bethesda, Maryland, USA.

PMID- 20806466
TI  - Proceedings of the 3rd Malmo Conference on Medical Imaging, 25-27 June 2009,
      Malmo, Sweden.

PMID- 20806468
TI  - [Complex evaluation of protein, purinic, carbohydrate and lipid metabolism in
      moderate and intense muscular activities].
AB  - The purpose of the current study was to investigate findings, peculiarities,
      parameters and indicators of protein, carbohydrate, lipid and purinic metabolism
      in the blood, erythrocytes and homogenate of femur muscles in case of moderate
      and maximal physical exertion. 24 male rats were studied. The above rats
      underwent muscular exertion in the form of loads during swimming. The load
      accounted for 10% of the body weight. Specific changes of metabolism due to the
      influence of moderate and maximal physical muscular exertion were revealed.
      Mechanisms of atherogenic effects in maximal muscular exertion are discussed.

PMID- 20806469
TI  - [Cellular reaction of the skin and underlying tissues on prolonged acupuncture
      needle introduction].
AB  - The changes of a skin and hypodermic are studied at the prolonged introduction
      (till 3 months) original acupuncture needles under a skin of an auricle and neck
      at rats by the technique Muhina M.M. In early terms in an introduction place
      develops an aseptic (or septic) inflammation reaching of peak in 1-2 weeks. On a
      measure reduction of inflammatory reaction activation of epydermis
      (keratinocites) which acquire from periphery an acupuncture needle is marked,
      isolating it from surrounding tissues and forming the implant channel
      (acustract). Formation process of acustract comes to the end through 2 - 2,5
      months.

PMID- 20806470
TI  - Improving oral healthcare delivery systems through workforce innovations: an
      introduction.
AB  - The objective of this paper is to describe the purpose, rationale and key
      elements of the special issue, Improving Oral Healthcare Delivery Systems through
      Workforce Innovations. The purpose of the special issue is to further develop
      ideas presented at the 2009 Institute of Medicine (IOM) workshop, Sufficiency of
      the U.S. Oral Health Workforce in the Coming Decade. Using the IOM discussions as
      their starting point, the authors evaluate oral health care delivery system
      performance for specific populations' needs and explore the roles that the
      workforce can play in improving the care delivery model. The contributing
      articles provide a broad framework for stimulating and evaluating innovation and
      change in the oral health care delivery system. The articles in this special
      issue point to many deficits in the current oral health care delivery system and
      provide compelling arguments and proposals for improvements. The issues presented
      and solutions recommended are not entirely new, but add to a growing body of work
      that is of critical importance given the context of wider health care reform.

PMID- 20806471
TI  - Oral health disparities and the workforce: a framework to guide innovation.
AB  - INTRODUCTION: Oral health disparities currently exist in the United States, and
      workforce innovations have been proposed as one strategy to address these
      disparities. A framework is needed to logically assess the possible role of
      workforce as a contributor to and to analyze workforce strategies addressing the
      issue of oral health disparities. METHODS: Using an existing framework, A
      Strategic Framework for Improving Racial/Ethnic Minority Health and Eliminating
      Racial/Ethnic Health Disparities, workforce was sequentially applied across
      individual, environmental/community, and system levels to identify long-term
      problems, contributing factors, strategies/innovation, measurable
      outcomes/impacts, and long-term goals. Examples of current workforce innovations
      were applied to the framework. RESULTS: Contributing factors to oral health
      disparities included lack of racial/ethnic diversity of the workforce, lack of
      appropriate training, provider distribution, and a nonuser-centered system. The
      framework was applied to selected workforce innovation models delineating the
      potential impact on contributing factors across the individual,
      environmental/community, and system levels. The framework helps to define
      expected outcomes from workforce models that would contribute to the goal of
      reducing oral health disparities and examine impacts across multiple levels.
      However, the contributing factors to oral health disparities cannot be addressed
      by workforce innovation alone. CONCLUSION: The Strategic Framework is a logical
      approach to guide workforce innovation, solutions, and identification of other
      aspects of the oral healthcare delivery system that need innovation in order to
      reduce oral health disparities.

PMID- 20806472
TI  - Private sector approaches to workforce enhancement.
AB  - OBJECTIVES: This paper addresses the private practice model of dental care
      delivery in the US. The great majority of dental care services are delivered
      through this model and thus changes in the model represent a means to
      substantially change the supply and availability of dental services. The two main
      forces that change how private practices function are broad economic factors,
      which alter the demand for dental care and innovations in practice structure and
      function which alter the supply and cost of services. METHODS: Economics has long
      recognized that although there are private market solutions for many issues, not
      all problems can be addressed through this model. The private practice of
      dentistry is a private market solution that works for a substantial share of the
      market. However, the private market may not work to resolve all issues associated
      with access and utilization. Solutions for some problems call for creative
      private - public arrangements - another form of innovation; and market-based
      solutions may not be feasible for each and every problem. This paper discusses
      these economic factors and innovation as they relate to the private practice of
      dentistry, with special emphasis on those elements that have increased the
      capacity of the dental practice to offer services to those with limited means to
      access fee-based care. RESULTS: Innovations are frequently described as new care
      delivery models or new workforce models. However, innovation can occur on an
      ongoing and regular basis as dental practices examine new ways to combine capital
      and human resources and to leverage the education and skill of the dentists to a
      greater number of patients. Innovation occurs within a market context as the
      current and projected economic returns reward the innovation. Innovation can also
      occur through private-public arrangements. CONCLUSIONS: There are indications of
      available capacity within the existing delivery system to expand service
      delivery. The Michigan Medicaid Healthy Kids Dental program is discussed as one
      example of how dental services to Medicaid insured children were effectively
      expanded using the private practice model.

PMID- 20806473
TI  - The dental safety net, its workforce, and policy recommendations for its
      enhancement.
AB  - OBJECTIVE: The dental safety net includes the facilities, providers, and payment
      programs that support dental care for underserved populations including those
      individuals disadvantaged by a variety of social, economic, and health
      conditions. Its components-health centers, dental schools, clinics, Medicaid
      oriented dental practices, free-care programs, hospital emergency rooms, and
      others-vary in availability, comprehensiveness, continuity, and quality. The
      objective of this overview is to identify options and opportunities for policy
      changes to enhance oral health professional workforce in the safety net. METHODS:
      Characteristics of the dental safety net and its components are reviewed and
      compared. RESULTS: Professionals who now staff the dental safety net are a small
      subset of US dental providers and few current trainees anticipate practicing in
      these programs. Therefore, the safety net will continue to confront workforce
      challenges. CONCLUSIONS: Multifactorial policy alternatives to increase the
      availability of dental professionals who care of the underserved include proposed
      changes in dental education, licensure, scope of practice for allied dental
      personnel, and federal and state financing of public insurance. Also needed are
      local efforts to establish social norms and activities among private dentists
      that engage more private practitioners in care of the underserved.

PMID- 20806474
TI  - Creating and maintaining oral health for dependent people in institutional
      settings.
AB  - The absolute number and percentage of the population of dependent individuals in
      institutional settings are growing dramatically in the United States. The current
      dominant office-based oral health delivery system is not adequately addressing
      the oral health needs of these populations and is unlikely to do so in the
      future. There are multiple challenges in providing oral health services for
      dependent people in institutional settings. To achieve improvements in the oral
      health of these populations, we must change the education of oral health
      professionals, educate staff in institutional settings about oral health,
      integrate oral health activities into general health and social service systems,
      use existing oral health professionals in new ways in community settings, develop
      new categories of oral health professionals, and reform oral health delivery and
      reimbursement systems. Developing new models of oral health services for
      dependent individuals in institutional settings may provide an opportunity to
      create a new paradigm of care based on integration of oral health services with
      general health and social services with an emphasis on prevention and health
      promotion activities.

PMID- 20806475
TI  - The challenge to delivering oral health services in rural America.
AB  - OBJECTIVES: This review identifies the challenges to oral health in rural America
      and describes areas of innovation in prevention, delivery of dental services, and
      workforce development that may improve oral health for rural populations.
      METHODS: This descriptive article is based on literature reviews and personal
      communications. RESULTS: Rural populations have lower dental care utilization,
      higher rates of dental caries, lower rates of insurance, higher rates of poverty,
      less water fluoridation, fewer dentists per population, and greater distances to
      travel to access care than urban populations. Improving the oral health of rural
      populations requires practical and flexible approaches to expand and better
      distribute the rural oral health workforce, including approaches tailored to
      remote areas. Solutions that involve mass prevention/public health interventions
      include increasing water fluoridation, providing timely oral health education,
      caries risk assessment and referral, preventive services, and offering behavioral
      interventions such as smoking and tobacco cessation programs. Solutions that
      train more providers prepared to work in rural areas include recruiting students
      from rural areas, training students in rural locations, and providing loan
      repayment and scholarships. Increasing the flexibility and capacity of the oral
      health workforce for rural areas could be achieved by creating new roles for and
      new types of providers. Solutions that overcome distance barriers include mobile
      clinics and telehealth technology. CONCLUSIONS: Rural areas need flexibility and
      resources to develop innovative solutions that meet their specific needs.
      Prevention needs to be at the front line of rural oral health care, with
      systematic approaches that cross health professions and health sectors.

PMID- 20806476
TI  - Envisioning success: the future of the oral health care delivery system in the
      United States.
AB  - The elimination of oral health disparities in the US will require enhancing
      access to oral health care services. The workshop convened in 2009 by the
      Institute of Medicine on the "US Oral Health Workforce in the Coming Decade"
      highlighted both the current workforce's failure to meet the nation's needs as
      well as the promising opportunities presented by various workforce strategies to
      significantly enhance access and improve oral health outcomes. In this article,
      we have briefly reviewed and expanded on the contributions in this special issue
      of the Journal of Public Health Dentistry, with the goal of identifying common
      themes and providing a framework for evaluation. There are several key areas
      where change is critically needed in order to ensure successful implementation of
      any new workforce models. These areas include a) the public and private financing
      of dental care, b) the dental educational system, and c) state and federal
      policies.

PMID- 20806477
TI  - [Continuing education without moderation].

PMID- 20806478
TI  - [Professional development in the logic of competency].

PMID- 20806479
TI  - [Professional development, from disciplinary logic to a logic of competence].

PMID- 20806480
TI  - [Putting in place a framework for the engagement of students, implications for
      teamwork].

PMID- 20806482
TI  - Proceedings of the conference Viral Safety and Extraneous Agents Testing for
      Veterinary Vaccines, Annecy, France, 25-27 October 2009.

PMID- 20806481
TI  - Transmission Of childhood tuberculosis risk factors associated with an
      unidentified index case and outbreak evolution in Barcelona (1987-2007).
AB  - The objective of the study was to examine the factors associated with
      unidentified tuberculosis (TB) index cases (1987-2007) and to describe outbreaks
      (2000-2007) of childhood TB cases in Barcelona, Spain. Contact tracing seems to
      be fundamental in index case identification, but improvement could be made among
      older children and cases of extrapulmonary TB or pulmonary TB with sputum
      microscopy results.

PMID- 20806483
TI  - Proceeding of the 10th International Meeting on Cholinesterases, Sibenik,
      Croatia, 20-25 September 2009.

PMID- 20806484
TI  - Proceedings from the 2009 International Berry Health Benefits Symposium.

PMID- 20806485
TI  - [Plastic adhesive drapes can increase the risk of surgical wound infections].

PMID- 20806486
TI  - [Should fibromyalgia, chronic fatigue syndrome and multiple chemical sensitivity
      be treated in psychiatric services?].

PMID- 20806487
TI  - [Myalgic encephalomyelitis-chronic fatigue syndrome is not a functional disease].

PMID- 20806488
TI  - [A bloody summer].

PMID- 20806489
TI  - New horizons for the methodology and physiology of training periodization: block
      periodization: new horizon or a false dawn?

PMID- 20806490
TI  - Disenrollment procedures. Final rule.
AB  - This document makes technical amendments to the Department of Veterans Affairs
      (VA) regulation concerning enrollment and disenrollment from the VA medical care
      system. It removes the "automatic enrollment" provision relevant to a 1998 trial
      enrollment program that has been discontinued. It also amends the regulation to
      reflect current VA practice and to update the address for documents mailed to the
      VA Health Eligibility Center. Finally, it provides an internet address for
      accessing VA Form 10-10EZ online.

PMID- 20806491
TI  - Medicare program; establishing additional Medicare durable medical equipment,
      prosthetics, orthotics, and supplies (DMEPOS) supplier enrollment safeguards.
      Final rule.
AB  - This final rule will clarify, expand, and add to the existing enrollment
      requirements that Durable Medical Equipment and Prosthetics, Orthotics, and
      Supplies (DMEPOS) suppliers must meet to establish and maintain billing
      privileges in the Medicare program.

PMID- 20806492
TI  - [Resection of the left pulmonary lobe via vertical incision of the sternum].

PMID- 20806493
TI  - [Complete resection of the residual left lung 17 years after left pneumonectomy].

PMID- 20806494
TI  - [Effect of Schistosoma japonicum Mr 22 600 particulated-antigen on dendritic
      cells and CD4+CD25+ regulatory T cells].
AB  - OBJECTIVE: To study the role of Schistosoma japonicum Mr 22 600 particulated
      antigen on dendritic cells (DCs) and CD4+CD25+ regulatory T cells. METHODS: In in
      vitro experiments, DCs were pulsed with Sepharose 4B coupling rSj22.6/26GST and
      soluble rSj22.6/26GST, respectively. The surface molecules of DCs were detected
      by flow cytometry and the function of DCs was detected by mixed lymphocyte
      reaction. For the reduction of CD4+CD25+ T cells, DCs pulsed with Sepharose 4B
      coupling rSj22.6/26GST and soluble rSj22.6/26GST, respectively, were co-cultured
      with CD4+ T cells isolated from the spleen cells. The percentage of CD4+CD25+
      Foxp3+ T cells in CD4+ T cells was detected by flow cytometry. In in vivo
      experiments, BALB/c mice were immunized with Sepharose 4B coupling rSj22.6/26GST,
      Freund's adjuvant emulsified rSj22.6/26GST, rSj22.6/26GST, Sepharose 4B, Freund's
      adjuvant and PBS, respectively. The percentage of DCs in draining lymph nodes and
      the percentage of CD4+CD25+Foxp3+ T cells in spleen cells were detected by flow
      cytometry. To analyze the inhibitory roles of CD4+CD25+ T cells on CD4+CD25- T
      cells, CD4+CD25+ T cells were separated from mice immunized with Sepharose 4B
      coupling rSj22.6/26GST and Freund's adjuvant emulsified rSj22.6/26GST,
      respectively, and co-cultured with CD4+CD25- T cells. The proliferation of cells
      was assessed by [3H] thymidine incorporation method. RESULTS: In vitro, the
      expression rate of the surface molecules of CD40, CD80 and CD86 on the soluble
      antigen pulsed DCs were (43.5 +/- 6.2)%, (37.7 +/- 0.1)%, and (71.4 +/- 1.4)%,
      respectively. But on the Sepharose 4B coupling antigen pulsed DCs, they were
      (31.2 +/- 5.4)%, (32.0 +/- 1.6)%, and (63.8 +/- 1.0)%, respectively, which
      suggested that the Sepharose 4B coupling rSj22.6/26GST had less stimulating roles
      on DCs maturation Furthermore, addition of DCs pulsed with Sepharose 4B coupling
      rSj22.6/26GST caused the expanding of CD4+CD25+ T cells. In vivo, immunization of
      Sepharose 4B coupling rSj22.6/26GST increased the number of CD4+CD25+ T cells.
      CD4+CD25+ T cells separated from Sepharose 4B coupling rSj22.6/26GST immunized
      mice had stronger inhibitory ability (cpm 1 420 +/- 335), compared with that of
      mice immunized with soluble antigen (cpm 3 558 +/- 147). CONCLUSION: In contrast
      to the Freund's adjuvant emulsified antigen, immunization with Sepharose 4B
      coupling rSj22.6/26GST increases the number of CD4+CD25+ T cells, which showed
      stronger inhibition on the CD4+ CD25- T cell proliferation, and the mechanism of
      which may be involved in DCs maturation.

PMID- 20806496
TI  - [Two cases of suspected cystic echinococcosis in spermatic cord].

PMID- 20806495
TI  - [Treatment of rats infected with Clonorchis sinensis using clinical
      administration regimens of tribendimidine, praziquantel and artesunate].
AB  - OBJECTIVE: To evaluate the efficacy in treatment of Clonorchis sinensis-infected
      rats using the administration regimens of tribendimidine, artesunate and
      praziquantel applied in clinical treatment of clonorchiasis. METHODS: The doses
      of tribendimidine, artesunate and praziquantel used in clinical treatment of
      clonorchiasis were converted to the doses used in rats by the method of equal
      effective dose conversion among different animals, while the administration
      regimens of the drugs were designed basing on the regimens used in clinical
      trials. Thus, the following dose schedules were set up, i.e., tribendimidine 16
      or 32 mg/(kg x d) x 1, 2 or 3 d (bid), 8 or 16 mg/(kg x d) x 3 d; artesunate 12
      mg/(kg x d) x 3 d (tid) and 16 mg/(kg x d) x 3 d (bid); praziquantel 143 mg/(kg x
      d) x 2 or 3 d (tid), 143 mg/(kg x d) x 2 or 3 d (bid), 47.7 or 71.5 mg/(kg x d) x
      3 d. 151 rats were divided into 2 batches and each rat was infected orally with
      50 metacercariae of C. sinensis. In the first batch of test, 79 rats were divided
      into 13 groups of 5-6 rats 5 weeks post-infection. Among them 6 groups were
      treated orally only with tribendimidine, artesunate or praziquantel, while other
      7 groups were treated with tribendimidine combined with artesunate or
      praziquantel, or praziquantel combined with artesunate. The remaining 8 untreated
      rats served as control. In the second batch of test, 72 rats were divided into 13
      groups of 5 rats. Among them, 7 and 6 groups were treated with tribendimidine and
      praziquantel, respectively, 6 weeks post-infection. The remaining 8 untreated
      rats served as control. Rats were sacrificed 14 days post-treatment, worms were
      recovered from the bile duct and the liver tissue. The mean worm reduction rate
      was calculated and compared among the groups by non-parametric method (Mann
      Whitney test). RESULTS: In the first batch of test, the mean worm burdens in rats
      infected with C. sinensis and treated orally with tribendimidine 16 or 32 mg/(kg
      x d) x 3 d (bid), praziquantel 143 mg/(kg x d) x 3 d (tid), or 143 mg/(kg x d) x
      3 d (bid) were significantly lower than that of the control (P < 0.01) with mean
      worm burden reductions of 94.2%-96.0%. No efficacy was seen when infected rats
      were treated orally with artesunate 12 mg/(kg x d) x 3 d (tid). But in those
      treated with artesunate 16 mg/(kg x d) x 3 d (bid), the mean worm burden was
      significantly lower than that of the control (P < 0.05) with a mean worm
      reduction of 57.2%. In combined treatment, the infected rats treated with
      tribendimidine 16 or 32 mg/(kg x d) x 3 d (bid) in combination with praziquantel
      143 mg/(kg x d) x 3 d(bid) or artesunate 16 mg/(kg x d) x 3 d (bid), the
      difference of mean worm burden between each combined treatment group and control
      group was statistically significant (P < 0.01) with mean worm reductions of 94.2%
      -99.4% which revealed that the worm reduction rate in combined treatment group
      was similar to the corresponding group treated with tribendimidine or
      praziquantel alone, but significantly higher than that of the group treated with
      artesunate alone. In infected rats treated with praziquantel 143 mg/(kg x d) x 3
      d (tid) plus artesunate 12 mg/(kg x d) x 3 d (tid) or praziquantel 143 mg/(kg x
      d) x 3 d (bid) plus artesunate 16 mg/(kg x d) x 3 d (bid), the mean worm burden
      reductions were 93.6% -100%. In the second batch of test, the efficacy of
      tribendimidine obtained from infected rats treated with the drug 16 or 32 mg/(kg
      x d) x 2 d (bid) and 3 d (bid), the difference of mean worm burdens between them
      was not statistically significant with mean worm reductions of 86.5%-95.1%. When
      rats were treated with tribendimidine 32 mg/(kg x d) x 1 d (bid), the mean worm
      reduction was 73.0%, while the dose of the drug was given to the rats at 8 or 16
      mg/kg daily for 3 days the mean worm reduction rates were 88.3%-92.6%. Treatment
      of praziquantel 143 mg/(kg x d) x 3 d (tid) resulted in a worm reduction of
      96.9%, if the treatment course reduced to 2 d, the rate was 63.2%. Similar
      results were obtained in rats treated with praziquantel 143 mg/(kg x d) x 2 d
      (bid) and 3 d (bid). Finally, administration of praziquantel at a daily dose of
      47.7 or 71.5 mg/kg for 3 d exhibited no effect against C. sinensis. CONCLUSION:
      When the dose schedules of tribendimidine, artesunate and praziquantel used in
      humans are converted to the doses for use in rats, tribendimidine and
      praziquantel exhibit satisfactory effect against C. sinensis, but artesunate
      shows no or less effect; the treatment course of tribendimidine can be reduced
      from 3 d to 2 d. Since tribendimidine and praziquantel used alone have endorsed
      high efficacy against C. sinensis in rats, combinations among the 3 drugs do not
      show better effect.

PMID- 20806497
TI  - [Screening and characterization of peptides specifically binding to the
      schistosomulum tegument of Schistosoma japonicum].
AB  - OBJECTIVE: To screen and analyze the peptides in 12 phage-display peptide library
      specifically binding to the schistosomulum tegument of Schistosoma japonicum.
      METHODS: A 12 phage-display peptide library was screened with the S. japonicum
      schistosomula as the target cells for biopanning by degrees, positive clones
      picked randomly were deduced by DNA sequencing. According the sequence seeing
      result, immunohistochemical staining was performed to determine the specificity
      of the phages to the tegument. To test their targeting efficacy, the interested
      phage clones were infused back to the mice infected with S. japonicum, mice were
      sacrificed 2.5 hours later, and the phage distribution in the liver and the
      tegument of schistosomula was appraised, respectively. RESULTS: After 3 rounds of
      biopanning, the phage recovery rate increased from 0.77 x 10(-8) to 0.75 x 10(
      5), indicating that the phage library was successfully enriched in the tegument
      of schistosomula. Seventy-five percent (15/20) of the analyzed sequences were
      identical with a sequence of QHPRIRKOOOOO. The immunohistochemical stainings
      showed this sequence specifically binding to the tegument. In vivo titering
      displayed that this sequence selectively targeted the tegument. CONCLUSION: The
      peptide of QHPRIRKOOOOO specifically binds to the schistosomulum tegument.

PMID- 20806498
TI  - [Protective immunity of Cs-Rho GTPase recombinant protein against Clonorchis
      sinensis infection].
AB  - OBJECTIVE: To study the protective immunity induced by recombinant vaccination of
      Cs-Rho GTPase of Clonorchis sinensis (Cs). METHODS: 20 SD-rats(8 weeks) were
      divided into two groups: A (recombinant protein experiment group) and B (PBS
      control group). Rats in group A were immunized with 1 ml protein of Cs-Rho GTPase
      (90 microg/ml) and 1 ml Freund's complete adjuvant through back and vola. 2 week
      later, the rats were given 1 ml protein of Cs-Rho GTPase (90 microg/ml) and 1 ml
      Freund's incomplete adjuvant, followed by 1 ml protein of Cs-Rho GTPase (90
      microg/ml) through intraperitoneal injection at 4, 7, 11 week after the first
      immunization. Rats in group B were given PBS in the same way as group A. All rats
      were challenged each with 50 Clonorchis sinensis metacercariae after the last
      immunization. 21 d later, fecal samples were collected from all rats for
      examining eggs (number of eggs per gram feces, EPG) in every 3-5 d. When eggs
      were found, the rats were sacrificed and worms were collected. IgG, IgG1 and
      IgG2a in sera were detected by ELISA before every immunization. Mean number of
      worms and eggs, and antibody level in the experiment group were calculated and
      statistically compared with the controls. RESULTS: The mean number of worms and
      EPG were (9.2 +/- 9.9) and (956.8 +/- 1 062.5) respectively in group A, which
      were significantly lower than those of group B [(23.25 +/- 15.75) and (3 062.5 +/
      2 501.8) respectively] (P < 0.05). The absorbency values of serum IgG (0.1,
      0.45, 0.65, 0.6, 0.65), IgG1 (0.1, 0.45, 1.1, 1.0, 1.1), and IgG2a (0.1, 0.7,
      1.1, 1.1, 1.1) before every immunization in group A were significantly higher
      than those of group B (almost always 0.1) (P < 0.05). CONCLUSION: Recombinant
      vaccination of Cs-Rho GTPase induces partial protective immunity against
      Clonorchis sinensis infection in rats.

PMID- 20806499
TI  - [Cloning, expression and identification of endothelial differentiation-related
      factor-1 gene of Schistosoma japonicum].
AB  - OBJECTIVE: To clone and express endothelial differentiation-related factor
      (SjEDF)-1 gene of Schistosoma japonicum, analyze its immunogenicity and the stage
      specific expression at different developmental stages of S. japonicum. METHODS:
      Total RNA were extracted from eggs, cercariae, schistosomula and adult worms. The
      housekeeping gene SjActin was selected as the internal reference. According to
      the open reading frame for SjEDF-1 gene (GenBank accession number: AY336498), a
      pair of primers were designed to amplify the SjEDF-1 gene which was subcloned
      into pET-28a vector. The recombinant plasmid SjEDF-1/pET-28a was transformed into
      E. coli BL21 and induced with IPTG for expression. The recombinant protein was
      purified with Ni-NTA resin. The immune rabbit sera was prepared by immunizing New
      Zealand white rabbits with purified recombinant SjEDF-1 protein. Western blotting
      was used to analyze the immunogenicity and the expression level of SjEDF-1 at the
      different developmental stages. RESULTS: The SjEDF-1 gene was detected with a
      band of 405 bp in eggs, schistosomula, female and male worms. The recombinant
      protein (rSjEDF-I) was expressed as inclusion bodies (M, 20 000). Western
      blotting analysis showed that the purified rSjEDF-1 protein was recognized by
      pooled sera of infected rabbits. The target protein was detected only in
      schistosomulum and adult worms. CONCLUSION: The recombinant protein (rSjEDF-I)
      shows certain immunogenicity, and is detected only in schistosomula and adult
      worms.

PMID- 20806500
TI  - [A case of amebic cerebral abscess postmortem diagnosed].

PMID- 20806501
TI  - [Protective efficacy induced by dendritic cells pulsed with GST in combination
      with CpG oligodeoxynucleotide against Schistosoma japonicum infection].
AB  - OBJECTIVE: To study the protective effects on the infection of Schistosoma
      japonicum in C57BL/6 mice induced by dendritic cells DCs pulsed with GST in
      combination with CpG oligodeoxynucleotide. METHODS: GST was purified and used to
      stimulate DC2.4 cell line. Antigen loading was analyzed by immunofluorescence
      method. Thirty-five C57BL/6 mice were divided into seven groups(5 mice per
      group). Mice in groups A, B, C, D and E were immunized subcutaneously with DCs,
      DCs treated with PSA, DCs pulsed with GST, DCs stimulated with GST+CpG ODN, DCs
      stimulated with CpG ODN, respectively. For the above five groups, each mouse
      received 100 microl cell suspension at the density of 10(7)/ml subcutaneously for
      three times at 2-week intervals. Each mouse of group F was immunized
      subcutaneously with 50 microg GST formulated in complete Freund's adjuvant first,
      and 50 microg, 10 microg GST respectively in incomplete Freund's adjuvant for the
      last two doses. Group G received PBS and served as control. Serum samples were
      collected 10 days after the final immunization, and were analyzed for specific
      antibodies by ELISA. At two weeks after the final immunization, each mouse were
      challenged by 30 +/- 1 cercariae of S. japonicum. Six weeks after infection the
      mice were sacrificed, and number of worms was counted. RESULTS: Light green
      fluorescence was observed in dendritic cells under the fluoroscope after pulsing
      with GST which indicated the protein loaded dendritic cells. The IgG level in
      groups C, D and F was 0.555 2 +/- 0.078 9, 0.715 0 +/- 0.052 3, and 2.127 0 +/-
      0.411 5, respectively, all higher than that of group G (P < 0.05). The worm
      reduction rate of group D was 53.3%, followed by group F (24.0%) and group C
      (21.3%). There was no significantly difference in the worm reduction rate between
      group D and groups F and C (P > 0.05). CONCLUSION: Dendritic cells pulsed with
      GST in combination with CpG oligodeoxynucleotide induce significant
      immunoprotection against the infection of Schistosoma japonicum.

PMID- 20806502
TI  - [Expression of the genes of adenosine deaminase, C-lectin and serpin in the
      salivary gland of Aedes albopictus].
AB  - OBJECTIVE: To express the genes of adenosine deaminase (ADA), C-lectin and serpin
      (serine protease inhibitor) in the salivary gland of Aedes albopictus. METHODS:
      Total RNA was extracted respectively from salivary glands of unfed (group SG) and
      engorged adult female Ae. albopictus mosquitoes (group BSG), female carcasses
      without head and salivary gland (group C), and male bodies without heads but with
      salivary glands (group M). After the primers for the genes of ADA, C-lectin and
      serpin were designed respectively according to the reported Ae. albopictus gene
      sequences in GenBank, real-time fluorescent quantitative RT-PCR was performed to
      detect expression level of these genes in different tissues of Ae. albopictus
      using beta-actin as internal reference. RESULTS: The mRNA expression level of ADA
      gene in the salivary glands from unfed adult female mosquitoes (group SG) was 545
      and 123 times higher than those of female carcasses without head and salivary
      gland (group C) and male bodies without heads but with salivary glands (group M)
      (P < 0.01). In group SG, C-lectin was 3 929 and 4 973 times higher than that in
      group C and M (P < 0.01). High level of mRNA coding for serpin was detected in
      group SG, being 1 911 and 2 978 times higher than that in group C and M (P <
      0.01). There was no significant difference in ADA, C-lectin and serpin mRNA
      levels between unfed and engorged salivary glands (P > 0.05). CONCLUSION: ADA
      gene can be expressed in various mosquito tissues, but higher in salivary glands.
      The genes of C-lectin and serpin have been highly expressed specifically in
      salivary gland of female mosquito.

PMID- 20806503
TI  - [Detection of anisakid nematodes by an SYBR green I real-time PCR].
AB  - OBJECTIVE: To establish an SYBR Green I real-time quantitative PCR method for the
      detection of anisakid nematodes with zoonotic potential from Taiwan Strait.
      METHODS: Anisakid larvae of six species (Anisakis simplex, A. physeteris,
      Raphidascaris trichiura, Contracaecum aduncum, C. muraenesoxi, and Contracaecum
      sp., a predominant species in fishes in the strait) were obtained from the guts
      of marine fishes and identified chiefly based on the morphological features. The
      ITS-2 rDNA sequences from the larvae were amplified by PCR using universal
      primers, then cloned and bidirectionally sequenced. According to these sequences,
      six specific forward primers were designed and synthesized. Specificity was
      determined by a series of conventional PCR respectively, the ITS-2 sequences
      amplified above were cloned into T vector which was subsequently transformed into
      E. coli DH5alpha. Following extraction and identification, the positive
      recombinant plasmid was used as quantitative template to generate standard curve
      and melt curve. Sensitivity and reproducibility were determined. RESULTS: All the
      6 standard curves established by the recombinant plasmids showed adequate linear
      relationship between threshold cycle (Ct) and template concentration. Melt curves
      were specific and all the 6 correlation coefficients were above 0.998. In the
      reproducibility test, the coefficients of variation (cv) of Ct values for
      detection of the 6 nematodes ranged between 0.18% and 2.80%, and the cv of the
      inter-assay ranged between 0.55% and 1.94%. The sensitivity of the real-time PCR
      was 1 x 10(2) copies/microl, about 100 times higher than the conventional PCR
      assays. The real-time quantitative PCR detection needed only 3.5 hours from the
      sample treatment to result report. CONCLUSION: An SYBR Green I fluorescent
      quantitative PCR has been developed for detecting anisakid nematodes with
      adequate sensitivity and specificity.

PMID- 20806504
TI  - [An indirect ELISA for the detection of Babesia caballi in equine animals].
AB  - OBJECTIVE: To clone and express BC48 gene of Babesia caballi, and to establish an
      indirect ELISA for the diagnosis of B. caballi in equine animals. METHOD: The
      genomic DNA of B. caballi was extracted from the infected donkey blood. BC48 gene
      was amplified by PCR. The PCR product was cloned into expression plasmid pET28a,
      and expressed in E. coli BL21 with IPTG induction. The recombinant protein was
      purified by Ni-NTA affinity chro-matography and was used as a diagnostic antigen
      to establish an indirect ELISA. The reaction conditions of the indirect ELISA
      were optimized. Specificity and sensitivity of this method were evaluated.
      RESULT: BC48 gene of B. caballi was 1 272 bp. The recombinant protein was
      expressed in E. coli BL21 as a soluble protein with a molecular weight of about
      M, 46 000 under induction of IPTG. The concentration of purified protein was
      12.98 mg/ml. The best conditions were obtained for the ELISA when the antigen
      concentration was 65 microg/ml with the serum dilution of 1:80. The protein
      specifically reacted with serum from donkey infected by B. caballi, but did not
      react with serum from donkey infected by Theileria equi (B. equi). Both ELISA and
      microscopy were applied to examine 17 donkeys in the field, 3 were positive by
      ELISA and 2 were found parasite-positive, respectively. CONCLUSION: The indirect
      ELISA method may be used to detect B. caballi infection in equine animals.

PMID- 20806505
TI  - Sequence analysis of Theileria annulata surface protein in Chinese isolates.
AB  - OBJECTIVE: To study the TaSP polymorphism in three Chinese isolates of Theileria
      annulata. METHODS: The isolates from Inner Mongolia Autonomous Region, Ningxia
      Hui Autonomous Region and Xinjiang Uygur Autonomous Region were cultured in RPMI
      1640 medium. TaSP gene was amplified from genomic DNA extracted from schizonts
      using polymerase chain reaction (PCR) and sequenced. Its amino acid sequence
      comparison was carried out with Clustal W2 multiple sequence alignment program.
      Molecular component and motif prediction were performed with online servers.
      RESULTS: The comparison of TaSP amino acid sequences of the three isolates showed
      that the central region (aa position 38-161) predicted to be the highly
      immunogenetic domain was polymorphic both in size and amino acid sequence, while
      the N-terminal (first 37 aa) and C-terminal (last 154 aa) parts were strongly
      conserved. Phylogenetic analysis and percentage identity revealed that the
      Chinese isolates were closely related to the isolates from Turkey, but quite
      different from those of India, Morocco and Tunisia. More importantly, variability
      was noticed among Chinese isolates, which caused both the location and number's
      differences of motif (casein kinase II phosphorylation sites) among three TaSP
      sequences. CONCLUSION: TaSP polymorphism exists in the Chinese isolates of T.
      annulata.

PMID- 20806506
TI  - [Liposomal amphotericin B cured two cases of visceral leishmaniasis tolerant to
      sodium antimony gluconate].

PMID- 20806507
TI  - [Molluscicidal effect of endophyte LL3026 from Buddleia lindleyana against
      Oncomelania hupensis].
AB  - OBJECTIVE: To research the molluscicidal effect, active components, thermal
      stability and light stability of endophyte LL3026 (Colletotrichum sp.) from
      Buddleia lindleyana METHODS: The molluscicidal effect of LL3026 against
      Oncomelania hupensis was determined as referring to the WHO guidelines for
      laboratory molluscicidal test, and the control experiments were performed with 1
      mg/L niclosamide or dechlorinated tap water. The active components from LL3026
      were extracted by different polar solvents. The thermal stability and light
      stability of its extracellular moiety was examined at different temperature (30
      100 degrees C), different time (30-150 min) and different illumination time (1-9
      d). RESULTS: Immersion test showed that the LC50 values for the LL3026 broth were
      50.11, 3.43, and 1.55 mg/L for 24, 48, and 72 h, respectively. The ether extract
      of LL3026 broth showed the best molluscicidal activity compared with other
      fractions. Treated with 25 mg/L ether extract for 24, 48, and 72 h, the mortality
      of O. hupensis was 100%. The molluscicidal activity of LL3026 broth had no change
      at 80 degrees C for 120 min, and the snail mortality was 100%. A 48-h exposure to
      LL3026 broth which placed in an artificial climate box with 3 600 1x illumination
      for 9 d resulted in 86.7% snail mortality. CONCLUSION: The fractions extracted
      from endophyte LL3026 isolated from B. lindleyana shows molluscicidal effect to
      O. hupensis.

PMID- 20806508
TI  - [Recent investigation and treatment of 1 060 advanced schistosomiasis cases in
      Zhejiang Province].
AB  - OBJECTIVE: To understand the current status of advanced schistosomiasis patients,
      deliver medical treatment, and improve the case management in Zhejiang Province.
      METHODS: The cases previously diagnosed or suspected as advanced schistosomiasis
      in the province were the subjects of the investigation. Questionnairing
      (demographical information, disease history, etc.), clinical examination (ascites
      syndrome, abdominal palpation), laboratory examination (blood biochemistry, anti
      Schistosoma japonicum antibody, eggs), and ultrasonography of the abdomen were
      used confirming the diagnosis. Treatment was given to the patients. RESULTS:
      There were 1 060 advanced schistosomiasis patients in 32 counties of 7
      prefectures in the province. Majority of them distributed in water network
      regions, and lived with poor economic conditions. The average age of the patients
      was (66.3 +/- 9.3), with 89.3% ranged from 50 to 80 years old. Clinically 71.3%
      of the cases were with splenomegaly, 27.6% with ascites, 0.9% cases of multiple
      granuloma in the colon and 0.2% cases with dwarfism. 1 023 patients (96.5%) had
      received medical treatments. 69.4% of the cases had serious complications with
      advanced schistosomiasis and 52.5% had concurrently disorders in other systems.
      71.1% of the patients had subjective symptoms and 65.2% had hepatosplenomegaly
      with hepatic fibrosis and dysfunction. The serum positive rate of anti-S.
      japonicum antibody was 15.7%. Stool hatching test and microscopy revealed no eggs
      in fecal samples, but 24 out of 38 cases were found metamorphic eggs by rectal
      biopsy. Three years' medical treatment improved the clinical conditions in 74.3%
      of the cases. CONCLUSION: Situation of the advanced schistosomiasis patients is
      quite critical. Treatment and care are urgently needed especially for those aged
      50 to 80 years old. [

PMID- 20806509
TI  - [Progress in development of new antischistosomal drugs in recent years].
AB  - It is estimated that 200 million people have suffered the infection with
      schistosomes in the world. The fact that treatment of schistosomiasis only relies
      on a single drug praziquantel does not adapt to the demand. Although praziquantel
      exhibits excellent therapeutic efficacy, it shows no preventive action to the
      infection. Therefore, development of new anti-schistosomal drugs has been
      received serious attention. In this paper the recent development of new
      antischistosomal drugs such as oxadiazole-2-oxides, mefloquine, etc. has been
      reviewed, and the process of their development and anti-schistosomal properties
      recounted.

PMID- 20806510
TI  - [Polysaccharide and molecular pathogenesis of Plasmodium falciparum].
AB  - In the interaction of Plasmodium falciparum with human cells, sporozoite adheres
      to the receptor of the liver endothelial cell, then invades to liver. Merozoite
      binds to the surface of red blood cells, and invades to erythrocyte. The adhesion
      of membrane protein of the infected erythrocytes to the surface molecules of
      vascular endothelial cell in the vital organs leads to the obstruction of blood
      circulation eventually. The adhesion is mediated by interaction between parasite
      derived ligands and the negative charged polysaccharides on the surface of host
      cells. This review is to discuss the molecular mechanisms in the host-parasite
      interactions.

PMID- 20806511
TI  - [Cerebral infection of sparganosis: a case report].

PMID- 20806512
TI  - [Protein analysis of Trichomonas vaginalis treated by Pulsatilla chinensis in
      vitro].
AB  - Water extract of Pulsatilla chinensis (PWE) (0.625 mg/ml) was added to the medium
      for the culture of Trichomonas vaginalis. After 2 h and 4 h treatment, the
      content and component of soluble proteins in the parasites were analyzed by SDS
      PAGE. A total of 28 protein bands was demonstrated. After treated with PWE for 2
      h, the content of 5 protein bands increased and that of 4 bands decreased
      significantly. Four hours later, a new protein band appeared in the
      electrophoretogram, and the content of 5 bands increased and that of other 5
      bands decreased.

PMID- 20806513
TI  - [The accessibility for anthelmintic administration by different supply patterns
      in mass deworming].
AB  - Questionnairing was performed in selected fields. Data were collected including
      the number of people who were getting/taking medicines, reasons for not
      getting/taking medicines, and a comparison was made on the rates of
      getting/taking drugs among three patterns of medicine supply. In the mode of drug
      receiving at public expense, the rates of getting drugs and taking drugs were
      98.4% and 94.1% respectively in Hainan province, 93.2% and 90.9% in Guizhou
      province. In the mode of drug-delivery at public expense, the rates of getting
      drugs and taking drugs were 97.5% and 96.4% in Hainan province, 98.8% and 96.5%
      in Hunan province. In the mode of drug-purchase at people' s own expense, the
      rates of getting drugs and taking drugs were 96.8% and 95.6% in Guizhou province,
      94.4% and 91.5% in Sichuan province. The reasons for not taking drugs included
      forgetting, drug-losing or unwell condition. Three patterns of drug supply can
      get satisfactory results through careful arrangement. The government can choose
      an appropriate pattern suited to local conditions.

PMID- 20806514
TI  - [Schistosome eggs in cystic lymph node].

PMID- 20806515
TI  - [Clinical analysis of 16 AIDS patients complicated with toxoplasmic
      encephalitis].
AB  - Sixteen AIDS patients complicated with toxoplasmic encephalitis (TE) were
      retrospectively analyzed between August 2008 to August 2009 with a mean age of
      (37.0 +/- 11.6) years. The most common clinical symptoms were headache (68.8%,
      11/16) and fever (62.5%, 10/16), and 6 with Babinski sign (37.5%). 81.3%(13/16)
      were with CD4+ cells < 200/mm. Both sera and CSF showed 62.5% (10/16) TOXO-IgG
      positive by ELISA. CT and MRI scan demonstrated bilateral and multiple lesions
      with marked peripheral edema effect, and an enhanced scanning showed small finger
      ring as the major feature. 15 patients got improved by either oral sulphadiazine
      tablets or sulphadiazine tablets plus clindamycin capsule, 10 cases received
      combined HAART treatment, and 1 case died with septic shock.

PMID- 20806516
TI  - [Construction of full-length cDNA library of erythrocytic stage Plasmodium
      vivax].
AB  - Blood samples were collected from vivax malaria patients without antimalarial
      drug therapy. After filtration through Plasmodipur filter to remove white blood
      cells, Plasmodium vivax-infected RBCs were enriched by Percoll. Total P. vivax in
      red blood cells was isolated. A full-length cDNA library of erythrocytic stage P.
      vivax was constructed by the SMART cDNA library construction kit. The volume and
      recombinant rate of the library were evaluated. The inserted fragments were
      identified by PCR amplification. The titer of cDNA library was 1.14 x 10(6). The
      length of inserted fragment ranged from 900 to 2 500 bp, and the recombination
      efficiency accounted for 97.2%.

PMID- 20806517
TI  - Ketan Desai and the Medical Council of India: the road to perdition?

PMID- 20806518
TI  - The "spurious drugs" gene and its pervasiveness.

PMID- 20806519
TI  - Supreme Court judgment on medical interrogation: on the just use of science and
      the ethics of doctors' participation in criminal investigation.

PMID- 20806521
TI  - The Mental Health Act 1987: Quo Vadimus?
AB  - Persons with mental illness have the right to a range of treatment and supportive
      services in the community. These need to be assured to them by law. While older
      legislations viewed persons with mental illness either as "being dangerous" or as
      "objects of charity", the current UN Convention on the Rights of Persons with
      Disability views them as "subjects with rights". This has led to an urgent relook
      at the Mental Health Act 1987, which has faced criticism ever since its
      enactment. The recently proposed amendments enlarge the scope of regulation to
      include diverse mental healthcare facilities and professionals; seek the setting
      up of a State Mental Health Review Commission; lay down guidelines for
      "independent" and "supported" admissions; and propose new sections for emergency
      and other treatments, physical restraint and discharge. The debate regarding
      these amendments ranges from whether an amendment of the MHA will suffice or
      whether a new Act is required; whether the amendments are sufficiently broad
      based or excessively focused on inpatient treatment; how mental illness is
      addressed in other Acts; who are key stakeholders, and, most important, whether
      the mechanisms for service provision have been adequately thought through. The
      process of initiating the amendments has been questioned by different
      stakeholders and highlights the need to bring about legislative change through
      adequate dialogue and collaboration.

PMID- 20806520
TI  - Ethics in human resource management: potential for burnout among healthcare
      workers in ART and community care centres.
AB  - This paper examines ethical dilemmas in providing care for people with HIV/AIDS.
      Healthcare providers in this sector are overworked, particularly in the high
      prevalence states. They are faced with the dual burden of the physical and the
      emotional risks of providing this care. The emotional risks result from their
      inability to control their work environment, while having to deal with the social
      and cultural dimensions of patients' experiences. The physical risk is addressed
      to some extent by post exposure prophylaxis. But the emotional risk is largely
      left to the individual and there is little by way of institutional responsibility
      for minimising this. The guidelines for training workers in care and support
      programmes do not include any detailed institutional mechanisms for reducing
      workplace stress. This aspect of the programme needs to be examined for its
      ethical justification. The omission of institutional mechanisms to reduce the
      emotional risks experienced by healthcare providers in the HIV/AIDS sector could
      be a function of lack of coordination across different stakeholders in programme
      development. This can be addressed in further formulations of the programme.
      Whatever the reasons may be for overlooking these needs, the ethics of this
      choice need to be carefully reviewed.

PMID- 20806522
TI  - Ethical issues in child and adolescent psychotherapy: a clinical review.
AB  - Child and adolescent psychotherapy has made great progress in recent years. With
      this progress, ethical issues have emerged that need to be addressed in the
      Indian setting. This article looks at various ethical issues in child and
      adolescent psychotherapy specific to Indian practitioners. The involvement of
      parents in psychotherapy often blurs therapeutic boundaries and issues related to
      confidentiality. Practitioners working in hospital and school settings are faced
      with similar problems. The advent of the internet and e-mail has resulted in new
      concerns for psychiatrists, related to communication via those media. Issues
      related to parenting, culture and development patterns, along with personal
      issues for the therapist, have been discussed.

PMID- 20806523
TI  - Consent in terminal sedation.
AB  - For the majority of patients at the end of life, their symptoms can be relieved
      through good palliative care. However, for an unfortunate few, these symptoms
      become intractable despite the best holistic interventions and in such cases
      terminal sedation is considered. The use of this intervention remains fraught
      with controversy, particularly around the subject of consent. A clinical scenario
      is used to propose that under such circumstances, given the physical and
      psychological stress to which these patients are subject, it is neither useful
      nor meaningful to ask for the patient's informed consent. Instead, physicians
      caring for such patients should act in the patient's best interests, in
      accordance with the Best Interest Principle, to alleviate such suffering.

PMID- 20806524
TI  - Healthcare reform in the USA, 2010: the rocky road ahead?
AB  - Historic legislation for healthcare reform in the United States was enacted in
      March 2010. Reforms in medical practice, payment for services, and access to care
      and insurance will be introduced by complex processes over time through 2019. The
      overriding goals of healthcare reform are cost containment and guaranteeing
      access to all Americans. The contentious political struggle that preceded the
      legislation is emblematic of the continuous struggle in American society to
      define who is worthy of services. Understanding the value framework for social
      and welfare provisions in American society is crucial to making sense of the
      piecemeal policy making characteristic of the development of healthcare over the
      past 50 years. Here some highlights of the reform and the complex organisation of
      American healthcare are discussed.

PMID- 20806525
TI  - Public health, preparedness and the World Health Organization response to swine
      flu in 2009.

PMID- 20806526
TI  - National Rural Health Mission: a failing mission.

PMID- 20806527
TI  - Boundary violations and the "curtain of culture".

PMID- 20806528
TI  - Combating plagiarism: a shared responsibility.
AB  - Scientific progress depends on the free dissemination of original thinking and
      research. With the evidence base formed by publication, investigators develop and
      implement additional studies, and policy makers propose new laws and regulations.
      The ramifications of this evidence can affect millions of lives and reallocate
      considerable resources for programmes or research. As such, it is incumbent on
      investigators to conduct rigorous research, which precludes engaging in
      scientific misconduct such as falsification, fabrication and plagiarism. This
      article addresses the causes and consequences of plagiarism and the processes by
      which plagiarism is discovered. It concludes by considering the responsibilities
      of members of the research community in preventing and addressing plagiarism.

PMID- 20806529
TI  - Tackling disinterest towards blood donation: need for urgent action.
AB  - The shortage of voluntary blood donors is a problem in many countries including
      India. Myths regarding the ill effects of blood donation are common and many
      precious lives are lost for lack of replacement donations. Urgent measures are
      warranted to eliminate myths in the community regarding blood donation in order
      to encourage voluntary donation.

PMID- 20806530
TI  - Strengthening blood ties.

PMID- 20806531
TI  - The contours of clinical research in India.

PMID- 20806532
TI  - Seeking better inter-departmental cooperation in healthcare settings.
AB  - Hospital healthcare is essentially teamwork. Frequently, however, one comes
      across incidents where inter-departmental cooperation is compromised. It can
      create an awkward situation for residents and other staff members involved in the
      healthcare system. We can recall many such incidents during our training. Studies
      have indicated that failure in "tightly coupled" organisational relationships
      between hospital departments imposes a threat to patient safety. Clear guidelines
      on how to manage certain situations should be in place, leaving no ambiguity as
      far as issues concerning patient management are concerned. A lot more needs to be
      done by administrators to avoid such incidents and to promote inter-departmental
      co-operation. In addition, more caution and effort by administrators, residents
      and faculty can help avoid such incidents.

PMID- 20806533
TI  - Inter-departmental cooperation needs education.

PMID- 20806534
TI  - Allocating scarce life support in a public health emergency.

PMID- 20806535
TI  - Boundary violations in patient care: need for evolving professional practice
      standards and training.

PMID- 20806537
TI  - Seeking information on doctors and advertising.

PMID- 20806536
TI  - Do we need two systems for postgraduate medical education in one country?

PMID- 20806538
TI  - Informed consent needs information.

PMID- 20806539
TI  - A comparative study of EGFR mutation screening methods in non-small cell
      carcinoma of lung.
AB  - Epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine
      kinase of the ERBB2 family that has important roles in the proliferation and
      metastasis of tumor cells. It is frequently overexpressed in common solid tumors
      and has become a favored target for orally administered small-molecule tyrosine
      kinase inhibitors (TKI) and monoclonal antibody-based therapy. Gain-of-function
      somatic mutations of the EGFR tyrosine kinase domain have been associated with
      the response of some patients with non-small-cell lung carcinoma to TKIs. We
      evaluated three methods of EGFR mutation analysis to identify an optimal assay
      for clinical testing based on comparison of diagnostic sensitivity, technical
      difficulty, and cost (Tab. 1, Fig. 1, Ref. 12).

PMID- 20806540
TI  - Ovarian folliculogenesis: detrimental effect of prenatal exposure to
      cyclophosphamide: a preliminary study.
AB  - AIM: To investigate whether cyclophosphamide interferes with ovarian
      folliculogenesis. METHODS: In this experiment, pregnant rats (n=12) were randomly
      assigned into two groups, control group (n=6) and cyclophosphamide treatment
      group (n=6). In the cyclophosphamide treatment group cyclophosphamide was
      injected intraperitoneally from day 10 of gestation till 20th day, at 2 mg/kg of
      body weight. The pregnant rats were sacrificed on gestation day 20 and the fetus
      was collected. The collected fetuses were processed for sectioning and stained
      with haematoxyline and eosin for microscopic observation of the ovaries. RESULTS:
      A meshwork-like appearance of mesenchyme with decreased number of somatic cells
      and absence of the majority of the germ cells in the ovarian follicles were found
      in treated fetus. Non-availability of primordial germ cells stopped the
      interaction between primordial germ cells and somatic supporting cells leading to
      nonproliferation and degeneration of somatic cells and fluid-filled vacant spaces
      in the meshwork -like arrangement of mesenchymal cells. CONCLUSION: We conclude
      that cyclophosphamide exposure prevents folliculogenesis by causing anovulation
      and results in infertility. The same detrimental effect might be seen in human
      fertility with environmental pollutants which are also metabolites of the drug
      (Fig. 2, Ref. 25).

PMID- 20806541
TI  - Factors influencing the intermediate outcome in patients with single-ventricle
      physiology after Fontan operation.
AB  - OBJECTIVE: This study was conducted to analyze the factors affecting the
      intermediate outcome following the Fontan procedure in the current era. METHODS:
      Between January 1992 and December 2008, 189 patients underwent Fontan procedure
      at a median age of 3.4 years (0.4-37 years). Single left ventricle was present in
      77 (40%) patients, right ventricle in 70 (37%), in 7 (3.7%) patients, the
      ventricular morphology was indetermined and in 35 (18.5%) a dominant systemic
      ventricle with smaller second ventricle was present. The Fontan procedure was
      performed using an atriopulmonary connection (n=5, 5.6%), lateral atrial tunnel
      (n=99, 52%) or extracardiac conduit (n=85, 45%). 97.4% of patients recieved
      fenestration. RESULTS: The hospital survival was 95% and five patients required a
      takedown of Fontan circulation. The survival at 1.5 and 10 years was 94%, 93% and
      92%, respectively. Multivariate analysis identified that the outcome was
      influenced by the diagnosis of a complete common AV canal (p = 0.015), duration
      of ventilation (p < 0.0001) and duration of pleural effusions (p = 0.003).
      Failure-free survival at 1.5 and 10 years was 95%, 92% and 89%, respectively. The
      overall freedom from reoperation was 73%. Risk factors for reoperation were
      preoperative pulmonary artery pressure and duration of ventilation. CONCLUSIONS:
      The Fontan procedure is associated with excellent operative and intermediate
      survival. Common atrioventricular canal, duration of pleural effusions and
      ventilation have an adverse influence on the intermediate outcome. Reintervention
      is associated with pulmonary artery pressure and duration of ventilation (Tab. 7,
      Fig. 3, Ref. 16).

PMID- 20806542
TI  - Growth rates are similar in potentially benign and malignant small renal masses
      detected incidentally.
AB  - OBJECTIVE: Generally small renal masses grow at slow rate; some of them do not
      exhibit any growth. Does it mean that they are less aggressive? The aim of our
      study was to compare the growth of enhancing, non-enhancing solid renal masses,
      angiomyolipomas and complex renal cystic masses < or =4 cm in diameter. MATERIALS
      AND METHODS: 12 patients with solid enhancing, 20 with solid non-enhancing, 8
      with angiomyolipomas and 25 with Bosniak II/IIF/III and IV masses were enrolled
      and prospectively studied during the surveillance period. The mean diameter of
      the lesion at presentation was 3.5; 3.1; 3.2 and 3.9 cm, the mean period of
      observation was 47; 48; 35 and 48 for each group respectively. All masses were
      detected incidentally. Progression rates (the largest diameter was calculated)
      were compared among the groups. RESULTS: The range and mean growth rates among
      all groups after one year of observation were (0.0-0.3; 0.2 cm); (0.0-0.3; 0.2
      cm); (0.0-0.4; 0.3 cm); (0.0-0.3; 0.1 cm); (0.0-0.2; 0.1 cm); (0.0-0.0; 0.0 cm)
      and (-0.6-0.0; -0.2 cm) for 7 groups respectively. Overall 55.4% of masses did
      not exhibit any growth. We did not monitor any pathological lymph node
      enlargement, distant metastases in any group of patients. Overall, 85% of masses
      that exhibited growth during the first year did so at the end of follow up.
      CONCLUSIONS: The vast majority of small solid and complex cystic renal masses
      exhibit similar slow growth rates. According to these results, urologists can not
      predict the biological potential of the mass based on radiographic criteria and
      growth rates only (Tab. 2, Ref. 12).

PMID- 20806543
TI  - Age-related diseases; degenerative aortic valve disease and osteoarthritis.
AB  - OBJECTIVE: To examine the relationship between degenerative aortic valve disease
      and osteoarthritis Background: Degenerative aortic valve disease (DAVD) and
      osteoarthritis (OA) are age-related degenerative diseases whose pathogenesis
      involves mechanical stress and local inflammation. METHODS: Forty-four patients
      with DAVD (Group 1) and 21 controls (Group 2) were included in this study, which
      was intended to investigate the similarity between the two conditions. The two
      groups were similar in terms of age, sex, body mass index, a history of
      hypertension, cholesterol levels, diabetes mellitus and cigarette consumption.
      RESULTS: The average age + standard deviation of the DAVD patients were 71.3 +/-
      7.5, compared to 67.5 +/- 10.6 in the control group. In radiological OA analysis,
      the Lane scale was employed in the lumbar region and the Kellgren-Lawrence scale
      in the knee joint. Comparison of Groups 1 and 2 revealed no difference in
      radiological OA in the lumbar region and knee joint. CONCLUSION: Our study has
      shown that there is no relationship between these diseases that increased with
      age. However, extensive studies examining pathogenic mechanisms are needed (Tab.
      2, Ref. 11).

PMID- 20806544
TI  - Epidemiology of hospitalized burn patients in Taleghani Hospital during 2003
      2007.
AB  - AIM: The objective of this study was to describe the epidemiology of burn
      injuries refered to Taleghani Burn hospital, Ahvaz and to provide information
      necessary for planning and implementing an effective prevention program. MATERIAL
      AND METHODS: The medical records of 6082 consecutive admissions for burn injury
      treated at Taleghani burn hospital over a five-year period (August 2003 to August
      2007) were reviewed. RESULTS: Our results shows that hospital stay in female was
      significantly longer than in male (p < 0.05). A positive significant correlation
      was observed between duration of hospital stay and %TBSA (chi2, p < 0.05). Of the
      6082 patients, 486 deaths were recorded. The overall mortality rate of
      hospitalized burns patients was 8%. Mortality rate in female was higher than in
      male (p < 0.05). Our data showed E. coli in urine culture and Pseudomonas
      aeruginosa in blood and wound culture was the predominant isolated bacteria.
      CONCLUSION: This study provides an inclusive overview of hospitalized burn
      patients at Taleghani burn hospital. Prevention programs for reducing the risk of
      burns are needed. Furthermore, high %TBSA and mortality and the presence of multi
      drugs resistant bacteria are major worrying problems in our hospital (Tab. 5,
      Fig. 2, Ref. 27).

PMID- 20806545
TI  - Concept of predictable disinfection in endodontics.
AB  - Factors influencing the appropriate time to obturate a tooth are the patient's
      signs and symptoms, pulp and periradicular status, degree of difficulty, and
      patient management. The current consensus is that one-step treatment procedures
      are acceptable in cases where the patient exhibits a vital pulp. The removal of
      normal or inflamed pulp tissue and performance of the procedure under aseptic
      conditions should result in a successful outcome because of the absence of
      bacterial contamination. Obturation at the initial visit also precludes the
      contamination as a result of leakage during the period between the patient's
      visits. When patients present with acute symptoms caused by pulp necrosis and
      acute periradicular abscess, the obturation is generally delayed until the
      patient is asymptomatic. The interappointment antimicrobial dressing is indicated
      before the definitive obturation (Ref. 15).

PMID- 20806546
TI  - Do we need new quality markers for chronic heart failure?
AB  - Guidelines are not cookbook medicine. Medical decisions for the treatment of
      chronic heart failure (CHF) are more determined by patient's characteristics than
      by knowledge of physicians or drug patterns. New quality markers are more
      favourable, because they have qualitative attributes (are more flexible and
      adaptable for each CHF patient due to considering objective reasons for deviation
      from guidelines) (Ref. 44).

PMID- 20806547
TI  - Health of Europeans twenty years after the fall of Berlin wall.
AB  - The failure of central planning in the totalitarian systems of the USSR and its
      satellites adversely affected not only the economy and social relations but also
      the population health. While in the countries with established democracy (DEM)
      the general health and the life expectancy (LE) steadily improved, in countries
      declaring socialism (SOC) the LE was stagnant and in the USSR even decreased.
      Dramatic changes in Russia after the demise of Soviet Union resulted in an
      extraordinary destabilization of LE that reached a minimum in 1994. Remarkably,
      even twenty years after the breakdown of the Iron Curtain there persists a gap in
      the general health between the DEM and the SOC regions of Europe. Within the
      territory of the former Soviet influence there are additional differences in LE:
      Central Europe is much better off than Russia and its neighbours. Main cause of
      relatively high mortality in the post totalitarian Europe is the cardiovascular
      disease (CVD). Among females about 80% difference in LE between DEM and SOC
      countries is related to premature CVD mortality. In SOC males compared to DEM,
      about 50% of the higher mortality is caused by CVD, 20% is related to external
      factors (trauma, suicide) and 10% is oncologic disorders. The main suggested
      cause of such excess mortality, besides a low socioeconomic level and limited
      funding for health care, is an improper life style: alcoholism, smoking and
      inadequate intake of protective nutrients. Alcoholism, especially binge drinking
      is a prominent factor in Russia, Belarus, Ukraine and in the Baltic Republics
      (Fig. 6, Tab. 4, Ref. 20).

PMID- 20806548
TI  - Microbiological and therapeutical aspects of pneumococcal diseases in the Slovak
      Republic.
AB  - Since 1983, multiresistant pneumococcal strains, mostly 14, 23F, 19A serotypes
      have been reported in Slovakia. A 15-year cooperation of specialists from various
      fields and the representatives of different institutions revealed that the
      pneumococcal infection problem in the Slovak Republic remains an important
      healthcare task. In the prospective multicentric microbiological and clinical
      analysis of otitis media acuta in children under 5 years, pneumococci were
      isolated in 45.9%, where 50.8% of strains were intermediate and fully resistant
      to penicillin and 47.5% resistant to macrolid antibiotics. Invasive pneumococcal
      infections, mostly meningitis and bacteremias, were observed in two studies.
      Penicillin resistance was higher in children under 5 years (52.8%), in comparison
      with other age groups. The dominant serotypes of childhood were 14, 19A and 6A,
      while in the age group above 65 there was a broad spectrum of serotypes
      confirmed. Serotype 14 is the most frequent serotype in physiologically sterile
      liquids and otitis media liquor in the Slovak Republic (Tab. 3, Fig. 5, Ref. 34).

PMID- 20806549
TI  - Remodelling of the femoral head after proximal femoral osteotomy for avascular
      necrosis associated with slipped capital femoral epiphysis.
AB  - Avascular necrosis is the most devastating complication associated with slipped
      capital femoral epiphysis. In this case report, we present the clinical and
      radiological outcome of two patients after proximal femoral osteotomy for
      avascular necrosis associated with slipped capital femoral epiphysis. The Iowa
      hip score was used to assess the function. Periodic radiographic observations
      showed no progression of the collapse, and bone remodelling of the necrotic
      femoral head. Our evaluation of patients who underwent proximal femoral osteotomy
      for avascular necrosis prior to collapse of the femoral head suggests that its
      use resulted in acceptable clinical outcome with bone remodelling of the necrotic
      area (Fig. 4, Ref. 16).

PMID- 20806550
TI  - Black esophagus: a rare autopsy case.
AB  - The black esophagus is a rare entity of an acute esophageal necrosis described at
      endoscopy and typical histological properties of a diffuse mucosal necrosis. The
      presented case was a 17-year-old girl; admitted to the hospital with an abdominal
      distantion and vomiting, who died soon after admittance. The case was
      investigated by local prosecutor, as the cause of the death was unknown; a
      forensic autopsy was mandated and later performed in our department. During
      autopsy on macroscopic examination an acute esophageal necrosis with black
      colored esophageal mucosa was detected. In this case report, we aimed to explain
      the autopsy findings, clinical presentation, histological appearance, risk
      factors and pathogenesis of the disease from the medico legal point of view (Tab.
      1, Fig. 1, Ref. 5).

PMID- 20806551
TI  - A case of relapsing pluriorificial erosive ectodermosis.

PMID- 20806552
TI  - [Clinical and epidemiological research in teaching hospitals].

PMID- 20806553
TI  - [Prevalence and associated risk factors of arterial hypertension in Sobremonte
      and Ojo de Agua Departments in Cordoba State].
AB  - Arterial Hypertension (AH) is a disease with multiple risk factors (RF), and it
      is one of the most important risk factor for cardiovascular diseases. The
      objective of this study was to determine the prevalence of AH in Sobremonte area
      and its correlation to other risk factors. The study was done in an special
      programme called "Solidarity in Health" (SIH) supported by the College of
      Medicine at the National University of Cordoba, which provided primary care to
      residents of Cachi Yaco (Sobremonte Department). It is an small village near
      Santiago del Estero province located in 226 km from Cordoba city. They went to
      the city and they examined the patients at the the "French and Berutti" school
      for nine consecutive years (2000-2008). Sobremonte area is the poorest deparment
      in the province of Cordoba and it has the highest rate of lowest socio-economic
      development, and a very deficient health care system.. The only hospital
      providing primary care is in San Francisco del Chanar, and the access is not
      free. The study involved the determination of the arterial pressure (AP)
      according to the seventh "JNC"criteria, body mass index (BMI), levels of alcohol
      consumption, exercise, salt consumption, diabetes and smoking in all the
      patients. Additionally, three water samples from different representative zones
      were collected and tested for sodium concentration. 471 patients were included.
      The incidence of AH was 43.5% of the patients. (51% men and 36% women). Higher
      incidence of AH was found in patients between 50 and 59 years old. There was a
      stadistical difference in the BMI, diabetes, and alcohol consumption between
      healthy patients and patients with AH. There was not any correlation between AH
      and exercise. We found higher levels of sodium in the water of this area and it
      was between 13-35 higher than in C6rdoba city and it was correlated with AH. We
      conclude that the increased sodium consumption is one of the most important risk
      factor of AH in this population.

PMID- 20806554
TI  - [Lupus nephritis].

PMID- 20806555
TI  - [Small intestinal plasmacytoid lymphoma. Clinical presentation with acute
      abdominal pain].
AB  - Primary tumors of the small intestine are rare; 15-20% of the cases are
      extranodal lymphomas from B or T cells. Higher Incidence occurs in patients
      between 21 and 50 years. The clinical symptoms are pain, intestinal obstruction,
      diarrhea, bleeding or perforated peritonitis. In high-grade lymphomas, the cells
      are large and pleomorphic, with immunoblastic and plasmacytoid features, and
      immunopositive for alpha chain immunoglobulins. We reported the case of a 56-year
      old patient presented with abdominal pain associated with intestinal perforation.
      Resections of a 9-centimetres-long segment in the small intestine was performed,
      which was covered by purulent plaques, with a perforation of 5 mm, surrounded by
      a greyish-white thick intestinal wall. It can be observed in the microscopy a
      proliferation of neoplastic cells arranged diffusely and with frequent mitosis.
      Large areas of immunoblastic and plasmacytoid configuration were evident. The
      immunomarcation was consistent with a lymphoma of large cells, immunophenotype B,
      with plasmacytoid development. We highlighted the clinical presentation like
      acute abdominal pain and its clinical and pathological characteristics,
      especially in the plasmacytoid development that should differ of the true
      plasmocytoma.

PMID- 20806556
TI  - [Gender and medicine: why broach this subject?].

PMID- 20806557
TI  - [Gender, medicine and health: some landmarks].
AB  - Well established in the English-speaking area, gender perspective in medicine
      doesn't seem to be yet very familiar to Swiss doctors. First, the main
      initiatives taken in Switzerland in order to develop this field are mentioned.
      Next, explanations are given about the origin of the distinction made since the
      seventies in the social sciences between gender--related to the social--and sex-
      related to the biological--when one refers to men's and women's situations; a
      distinction officially introduced in medicine two decades later. After an
      evocation of the main historical steps leading to the constitution of Gender
      Health-Gender Medicine field, this article concludes with a picture of this
      approach, which relevance is nowadays underlined by the WHO as well as by other
      official instances.

PMID- 20806558
TI  - [Sexual health: variability in Switzerland and Europe].
AB  - Sexual Health is interrelated with both, sex and gender, through its biological
      dimension, its connection with cultural conventions, and its impact on women's
      health. Reproductive factors are presented from two cohorts, the Swiss SAPALDIA
      study and the European Community Respiratory Health Survey. Reproductive
      characteristics vary considerably across Switzerland and across Europe. A shift
      is observed towards lower ages at menarche and higher ages at menopause in
      younger cohorts. Smoking is the most important determinant of an early menopause.
      These secular trends imply that there will be changes also in the prevalence of
      diseases associated with age at menopause such as breast cancer and
      cardiovascular diseases.

PMID- 20806559
TI  - [Being a doctor: the influence of gender on the career choices and prospects].
AB  - Gender studies of a profession focus on the work distribution between men and
      women. Sociologists started to study the medical profession in the 80s only.
      Since it was male-dominated female doctors had no choice but adjusting their
      behavior to that of men. Nowadays, the majority of the young people interested in
      becoming a doctor are women. It is mandatory to gain insight into the demographic
      specificities of the medical population working in a large university hospital
      (according to sex, age, as well as to the level within the medical hierarchy). It
      is also important to analyze the key elements that differentiate male and female
      in their relationship to work and promotion. Finally, it is urgently necessary to
      change our organizations as well as our practices in order to be able to take
      into account these major changes of the medical demography.

PMID- 20806560
TI  - [Interactions between patients and physicians: why should we care about gender
      issues?].
AB  - This article presents the major findings of research on medical interactions from
      a gender perspective. Male and female physicians give the same amount of medical
      informations to their patients, but male physicians discuss less the psychosocial
      aspects of the illness. Male physicians ask less medical and psychosocial
      questions, and patients provide them with less information. Female physicians
      adopt more partnership-behaviors and display more affiliative nonverbal
      behaviors. Patients behave less dominantly with male than with female physicians.
      Finally, male patients are given less signs of empathy and receive less
      information, whatever the gender of the physician.

PMID- 20806561
TI  - [Hypertension: is the actual definition adapted to women?].
AB  - The control of blood pressure in men and women differs due to different
      physiological pathways. Moreover, conditions increasing the risk of hypertension,
      such as pre-eclampsia, exposure to oral contraceptives are specific to women. Men
      have a higher blood pressure than women from pubertal growth to advanced age.
      However, the definition of hypertension (blood pressure--140/90 mmHg) is the same
      for adult men and women. The management of hypertension should be based not only
      on the level of blood pressure, but also on the global cardiovascular risk. Sex
      is included in the global evaluation of the cardiovascular risk.

PMID- 20806562
TI  - [Addiction: are women and men equal?].
AB  - When illicit drugs are taken, men and women have a different biological response
      to drug used. Likewise, gender differences show more stigmas, more complex
      familial environment, and more history of sexual abuse for drug addicted women.
      The expression of psychiatric co-morbidities differs according to gender, with
      increased mood disorders, eating disorders, anxiety, and post traumatic disorders
      among drug addicted women.

PMID- 20806563
TI  - [More HIV-positive women are referred to a medication adherence clinic than men].
AB  - HIV-positive patients with antiretroviral medication adherence issues are
      referred to an outpatient adherence clinic. Surprisingly, two-third of referred
      patients are women although more than 60% of the patients at the Infectious
      Disease Outpatient service are men. Women seem to be referred because of specific
      social factors: children at home, black sub-Saharan ethnicity, difficulties in
      medication and disease management due to stigmatization. Literature is poor and
      controversial and it is not possible to conclude whether medication adherence
      varies with gender. However, recent data seem to show that reasons for
      nonadherence vary according to gender.

PMID- 20806564
TI  - [Health status and care giving needs in the elderly: gender related differences].
AB  - The health status and need for care differ depending on the gender. The most
      notable differences are life expectancy, life expectancy in good health and the
      prevalence of geriatric syndromes or chronic illnesses. Some social health
      determinants (social isolation or financial precariousness) seem to act as risk
      factors for vulnerability, mostly amongst old or very old women. Through some
      examples of differences between men and women in terms of health and caregiving
      needs, this article tries to heighten the awareness of health professionals to a
      gender based approach of the elderly patient in order to promote the best
      possible equity in healthcare.

PMID- 20806566
TI  - [Normality of the libido (asexuality)? 3].

PMID- 20806565
TI  - [Health in prison: shared vulnerability between detainees and health
      professionals].
AB  - In prison, the health professional has to take the sanitary needs of a temporary
      of chronically vulnerable population. His practice has to meet laws and
      recommendations, as well as the field reality and its numerous constraints. This
      puts him in a "shared vulnerability and stigmatization". He attempts to maintain
      or restore a health status in a deteriorating environment, at least
      psychologically. He is in the penitentiary world's eye which he depends upon in
      many ways to achieve his mandate. His activity is scarcely known and recognised
      by his peers from whom he can be very out of touch. To ensure a humanistic,
      efficient and equivalent-of-care practice, the health professional must rely on
      sound knowledge of general healthcare, ethics, deontology and medical laws. Basic
      and continuous training is a mainspring, like networking and development of
      federal recommendations.

PMID- 20806567
TI  - [Memory failures].

PMID- 20806568
TI  - [Bioethics: has Kant finally been reduced to silence? 4].

PMID- 20806569
TI  - [Diagnosis and treatment of iron deficiency without anaemia].

PMID- 20806571
TI  - [The life of others, physicians and medicine].

PMID- 20806570
TI  - [Recidivism of sexual crimes: what can be done? 2].

PMID- 20806572
TI  - Providing more bang for the buck.

PMID- 20806573
TI  - Costs of turnover & benefits of retention.

PMID- 20806574
TI  - Nurses face special healthcare challenges when caring for prisoners.

PMID- 20806576
TI  - How do you ensure that prisoners with cancer receive hospice care?

PMID- 20806575
TI  - Cancer care behind bars.

PMID- 20806577
TI  - Complementary and alternative medicine use in cancer survivors.

PMID- 20806578
TI  - ALK inhibitor has high response in patients with NSCLC.

PMID- 20806579
TI  - Communication.

PMID- 20806580
TI  - What was his thinking?

PMID- 20806581
TI  - High learning curve for transplant patients. Patients works to educate patients,
      physicians and the public.

PMID- 20806582
TI  - Why pick on propoxyphene? The evidence demands it.
AB  - While propoxyphene may have filled a niche when it was first marketed in 1957,
      newer, safer agents are now available. Multiple experts list the drug as one to
      avoid in the elderly patient. Evidence-based practice requires its use be
      minimized, especially in individuals over the age of 65.

PMID- 20806583
TI  - Female hydrocele of canal of nuck.
AB  - Hydrocele of the canal of Nuck is a very rare condition in females. The processus
      vaginalis within the inguinal canal forms "the canal of Nuck" in females,
      homologous to the processus vaginalis in males. Failure of obliteration of the
      processus vaginalis results in either a direct or an indirect inguinal hernia or
      if a sac of serous fluid is retained, it forms a hydrocele. Very little has been
      reported on this condition in the literature. We present a case of hydrocele of
      canal of Nuck in an 8-year-old female.

PMID- 20806584
TI  - Apparent life-threatening event (ALTE): an overview.

PMID- 20806585
TI  - Tackling a long-term issue.

PMID- 20806586
TI  - All change on the training front.

PMID- 20806587
TI  - A death before life.
AB  - Updated guidelines on stillbirths say that parents should be given the option of
      holding their baby.

PMID- 20806588
TI  - Looking from the outside in.
AB  - A housing and care provider for older people has taken the unusual step of
      employing a nurse to manage end of life care.

PMID- 20806589
TI  - Handle with care.
AB  - Epidermolysis bullosa (EB) is a genetically inherited condition that can lead to
      significant disability, but specialist nurses can help.

PMID- 20806590
TI  - Moving out of control.
AB  - Dystonia, a distressing movement disorder causing twitches and spasms, is often
      not recognised by health professionals.

PMID- 20806591
TI  - One falls, we all fall.

PMID- 20806592
TI  - Delivery debate.

PMID- 20806593
TI  - Early psychosis: raising awareness among non-mental health nurses.
AB  - People developing psychosis often seek help several times before receiving
      effective support and treatment, and frequently present to general healthcare
      staff. Therefore, awareness and knowledge of early psychosis among non-mental
      health nurses should be promoted. This article aims to provide an overview of
      psychosis, including signs and symptoms of the condition. Nurses need to be able
      to direct people displaying signs of early psychosis to the most appropriate
      services for timely assessment, support and treatment.

PMID- 20806594
TI  - Mental health nursing students' views of pre-registration nursing.
AB  - AIM: To inform the implementation phase of the Nursing and Midwifery Council
      (NMC) review of pre-registration nursing by documenting the change priorities as
      perceived by a group of mental health students. METHOD: The sample comprised 34
      students from one pre-registration mental health nursing cohort. A questionnaire
      was used to obtain views on the six features the students would like to change
      and the six features they valued most about the pre-registration nursing course.
      FINDINGS: The students' views were analysed in relation to the phase two criteria
      of the NMC review, and the results were listed in rank order. The evaluative
      comments were grouped into two themes: 'clinical placement experiences' and
      'views on learning and teaching strategies'. The students' main change priority
      was the need to enhance mentor support and the most valued feature was the
      variety of, and work involved in, clinical placements. CONCLUSION:
      Recommendations included a physical care skills programme that is specific to
      mental health; field (discipline)-specific competencies that reflect
      interprofessional work in mental health; and support provided by mentors and sign
      off mentors that complies with the NMC standards.

PMID- 20806595
TI  - Reducing the risk of respiratory disease in overseas travellers.
AB  - This article addresses the risk of respiratory illness for those travelling
      overseas. It considers emerging disease risks, particularly the influenza virus,
      as well as vaccination and vulnerable populations. Resources to help
      practitioners provide pre-travel advice in line with best practice in travel
      health are discussed.

PMID- 20806596
TI  - Alcohol misuse.

PMID- 20806597
TI  - Follow my lead.

PMID- 20806598
TI  - Good, but could do better.

PMID- 20806599
TI  - In the zone for best practice.

PMID- 20806600
TI  - Acute need for regulation.

PMID- 20806601
TI  - Education review to ensure all nurses can care for all patients.

PMID- 20806602
TI  - Patient safety agency among the NHS organisations dismantled by Whitehall.

PMID- 20806603
TI  - Scarce support changes lives.
AB  - Patients with rare diseases often feel isolated and can struggle to find
      information, but nurse specialists can help.

PMID- 20806604
TI  - Innovation in oncology.
AB  - Nurses are undertaking specialist procedures to improve the patient experience.

PMID- 20806605
TI  - Spiritual gaze.
AB  - A new book offers nurses insights into spirituality and tools enabling them to
      assess this aspect of patient care.

PMID- 20806606
TI  - Back to where we started.

PMID- 20806607
TI  - Food for thought.

PMID- 20806608
TI  - Medicines management.

PMID- 20806609
TI  - A framework to support safe blood transfusion practice.
AB  - In response to reports of fragmentation in care, treatment delays and concern
      over the safety of patients receiving blood transfusion support, a collaborative
      project between NHS Blood and Transplant and the Scottish National Blood
      Transfusion Service explored the feasibility of nurses and midwives extending
      their role to prescribe blood components. The project identified that there were
      no legal barriers to role development and, following extensive consultation, a
      governance framework to support safe practice is now available for all NHS trusts
      and boards.

PMID- 20806610
TI  - Inclusion of lay people in the pre-registration selection process.
AB  - The Nursing and Midwifery Council recommends that pre-registration nurse
      education programme providers involve lay people in the student selection
      process. The School of Nursing and Midwifery at Keele University undertook a
      project to develop and evaluate the inclusion of lay people in the pre
      registration recruitment and selection process. This article discusses the
      development and evaluation of the project and provides recommendations for
      practice.

PMID- 20806611
TI  - Developing patient group directions for medicines management.
AB  - This article explores the development and use of patient group directions in the
      supply and administration of medicines. It provides an overview of the
      classification of medicines and differentiates between a patient specific
      direction and a patient group direction. The use of patient group directions in
      the NHS and private sector, and the medicines that can be included in such a
      directive, are discussed.

PMID- 20806612
TI  - Meningitis.

PMID- 20806613
TI  - A confident future.

PMID- 20806614
TI  - Fair play in practice.

PMID- 20806615
TI  - Work-life in the balance.

PMID- 20806616
TI  - Tumor fever, paraneoplastic leukocytosis and necrotic liver metastases: a triad
      worth remembering.
AB  - Arriving at the diagnosis of tumor fever may prove difficult for the clinician
      and should always be based upon investigations that exclude other potential
      causes of fever. Timely recognition of this entity is essential for the effective
      delivery of care to cancer patients. In solid malignancies, tumor fever is
      commonly associated with rapidly progressive metastatic disease and a limited
      survival. Liver metastases are present in many of these patients and some of them
      may display significant systemic inflammation. We report two unique patients with
      adenocarcinoma of the lung associated with tumor fever, necrotic liver metastases
      and granulocyte-colony stimulating factor (G-CSF) driven leukocytosis.

PMID- 20806617
TI  - Human dermal tissue allograft use in treating chronic pilonidal sinus.
AB  - A study was conducted to try to improve upon existing conservative techniques in
      the treatment of chronic pilonidal sinus by using human dermal tissue allograft.
      A prospective study of 46 consecutive patients undergoing 47 operations for
      pilonidal disease was conducted by three surgeons. All patients underwent a
      conservative surgical technique with injection of human dermal tissue allograft
      and primary wound closure on an ambulatory basis. Sixty percent of patients
      required no postoperative narcotic use. Eighty-five percent missed no work or
      school. Sixty-six percent healed primarily. Thirty-three percent of patients
      developed minor wound complications that quickly responded to suture removal and
      drainage. There were no wound failures. The recurrence rate was 11% with a median
      follow-up of 15 months. This study demonstrates that primary closure is possible
      when combined with a conservative technique in treating uncomplicated pilonidal
      disease. This operative approach merits further investigation.

PMID- 20806618
TI  - Poststreptococcal cutaneous leukocytoclastic vasculitis: a case report.

PMID- 20806619
TI  - Intrathoracic lymphadenopathy: sarcoidosis or metastatic seminoma? The diagnostic
      dilemma revisited.
AB  - There exists a rare enigmatic relation between testicular germ cell tumors
      (particularly seminoma) and granulomatous inflammation of lymph nodes and organs
      akin to sarcoidosis. We report a young patient with stage I testicular seminoma
      followed by close surveillance after radical orchidectomy, who developed hilar
      and subcarinal lymphadenopathy more than two years after the original diagnosis.
      A mediastinal biopsy was consistent with noncaseating granuloma with no evidence
      of tumor. Our case highlights the importance of histologic confirmation of the
      etiology of lymphadenopathy in these cases. We reiterate that histological
      examination remains the cornerstone for establishing a definite and accurate
      diagnosis of testicular seminoma relapse.

PMID- 20806620
TI  - Pharmacological treatment of bipolar depression.

PMID- 20806621
TI  - Errors in delivery of cancer genetics services: implications for practice.
AB  - Advances in genetics have prompted recommendations that all healthcare providers
      perform genetic counseling and testing. Some experts are concerned about
      potential negative outcomes from cancer genetic testing performed without genetic
      counseling by certified genetics professionals. We report a national series of
      cases illustrating negative outcomes of cancer genetic testing performed without
      counseling by a qualified provider. Three major patterns emerged from analysis of
      these cases: 1) Wrong genetic test ordered, 2) Genetic test results
      misinterpreted, and 3) Inadequate genetic counseling. Negative outcomes included
      unnecessary prophylactic surgeries, unnecessary testing, psychosocial distress,
      and false reassurance resulting in inappropriate medical management. CONCLUSION:
      With the complexities of cancer genetic counseling and testing, it may be
      unrealistic to expect all clinicians to provide these services. A more realistic
      approach is better provider education and a framework in which healthcare
      providers identify patients who would benefit from a referral to a certified
      genetic counselor or experienced cancer genetics professional.

PMID- 20806622
TI  - Humanism in medicine: When the patient is not quite a patient, and the doctor is
      not quite a doctor.

PMID- 20806623
TI  - If Flexner had listened to Osler.

PMID- 20806624
TI  - Unsolved problems of disorders of the gastrointestinal tract: emotions and mental
      reactions. 1960.

PMID- 20806625
TI  - Fathers.

PMID- 20806626
TI  - Connected or detached?

PMID- 20806627
TI  - Accountable care organizations.

PMID- 20806628
TI  - Of politics and the primaries.

PMID- 20806629
TI  - Response to primary care: building the health-care institutions of the future.

PMID- 20806631
TI  - De-mystifying the complex world of dental practice purchases and sales: new
      strategies to accomplish your goals.

PMID- 20806630
TI  - Patient's page. What is tooth enamel?

PMID- 20806632
TI  - Prevention of early childhood caries: the possiblities of fluoride varnish.

PMID- 20806633
TI  - Preparing the profession to care for youngsters with special health care needs.
AB  - The complex issues involved in providing dental services to the increasing
      numbers of youngsters with special health care needs require the preparation of
      students and practitioners to meet these developments. A review of the changes in
      dental school requirements, the extent of needed services, the increased costs,
      and a challenge for current practitioners is presented.

PMID- 20806634
TI  - Three quick fixes for broken appointments.

PMID- 20806635
TI  - Oral pathology. Benign migratory glossitis.

PMID- 20806636
TI  - It's not a crisis.

PMID- 20806637
TI  - Health care reform.

PMID- 20806638
TI  - Dental trauma.

PMID- 20806639
TI  - Disease lottery revealed in end of life care provision.

PMID- 20806640
TI  - Do you provide equal healthcare to people with learning disabilities?

PMID- 20806641
TI  - Measuring general hospital staff attitudes towards people with learning
      disabilities.
AB  - People with learning disabilities often experience health inequalities and
      barriers to healthcare services as a result of poor communication and
      discriminatory attitudes. We developed an educational package for healthcare
      staff as well as an attitude questionnaire to measure the impact of this
      training; the questionnaire is called the Attitudes of Secondary Healthcare
      Personnel Toward People with Severe Learning Disabilities (ASH-LD). This article
      describes the process of designing and piloting the ASH-LD questionnaire, and how
      it will be used to measure the effect of the planned training on staff attitudes.

PMID- 20806642
TI  - Fit for life: promoting healthy lifestyles for adults with learning disabilities.
AB  - People with learning disabilities often experience health inequalities and poorer
      health than the general population. This article describes the development of an
      exercise group for people with learning disabilities in North Devon.

PMID- 20806643
TI  - Obesity in people with learning disabilities: possible causes and reduction
      interventions.
AB  - Obesity is more prevalent in people with learning disabilities than the general
      population, contributing towards health inequalities and higher risk of
      cardiovascular and cerebrovascular disease. This article discusses possible
      causes of this higher prevalence and examines interventions to reduce obesity and
      associated risks. It also outlines key points to consider when dealing with
      adults with learning disabilities, such as assessing mental capacity to consent
      to specific interventions. The importance of multidisciplinary team working with
      a range of professionals and specialists, and ensuring a consistent approach are
      also stressed.

PMID- 20806644
TI  - How to diagnose and manage physical complications related to alcohol misuse.

PMID- 20806645
TI  - The high impact actions for nursing and midwifery 5: protection from infection.
AB  - Four out of every five urinary tract infections can be traced to indwellng
      catheters. If the number of these infections is to be reduced significantly,
      nurses need to implement best practice for catheter care, and only catheterise
      patients when absolutely necessary.

PMID- 20806646
TI  - How mindfulness based stress reduction can reduce anxiety after alcohol
      abstinence.

PMID- 20806647
TI  - Depression 1: identifying the condition and offering initial treatment for
      adults.
AB  - Nurses must ensure their practice remains up to date and that they are aware of
      changes in the evidence base for managing depression. This two part unit on the
      updated National Institute for Health and Clinical Excellence guideline on
      depression outlines some of the main areas that were updated and the implications
      for nursing practice.

PMID- 20806648
TI  - Stop passing the buck--patient safety is nurses' problem too.

PMID- 20806649
TI  - If you're 'fat' why not throw away the chocolate bar?

PMID- 20806650
TI  - Development and testing of nurses information systems use instrument.
AB  - Information systems provide nurses with a variety of resources to facilitate
      their work. Nurses' use of information systems changes the way they collect
      assessment data, and plan and implement patient care. However, a reliable and
      valid instrument for measuring nurse's use of information systems does not
      currently exist. This study examined the development and psychometric testing of
      a measure of nurses' information systems use, the Information Systems Use
      Instrument (ISUI). A random sample of 570 nurses working in hospitals, providing
      direct patient care and using at least one information system completed the study
      questionnaire. The internal consistency reliability was .82. Exploratory factor
      analysis, using principal components extraction and varimax rotation, revealed
      that all seven items loaded cleanly and strongly on a single factor. The ISUI
      showed sufficient evidence for its psychometric properties to encourage its use.

PMID- 20806652
TI  - Measuring perceived mutuality in women with eating disorders: the development of
      the connection-disconnection scale.
AB  - This article describes the development and psychometric testing of the Connection
      Disconnection Scale (CDS), the only self-report measure designed to assess
      perceived mutuality experienced in close relationships by women with eating
      disorders. Item development was informed by relational-cultural theory and focus
      groups with patients and recovered individuals. Content and construct validity,
      test-retest reliability, and internal consistency were examined in samples of
      female outpatient (n = 131) and partial hospitalization (n = 85) patients. Factor
      analysis with promax rotation for each version of the CDS in outpatients resulted
      in a single-factor model explaining 77.53% of the variance for CDS-Mother, 71.86%
      for CDS-Father, 77.79% for CDS-Partner, and 67.67% for CDS-Friend. Cronbach's
      alphas ranged from .97 to .99 for both samples. Overall, the CDS demonstrated
      good discriminant and convergent validity with moderate to strong correlations
      between CDS parent forms and the Parental Attachment Questionnaire, Dyadic
      Adjustment Scale, and the Social Support Questionnaire. Regression equations
      revealed that scores on CDS parent forms were inversely related to several
      subscale scores on the Eating Disorders Inventory-2. The CDS is a reliable and
      valid measure of perceived mutuality that can enrich relational understanding of
      the etiology and treatment of eating disorders in women.

PMID- 20806651
TI  - Development of the Huntington disease family concerns and strategies survey from
      focus group data.
AB  - Health concerns and management strategies among families of young and middle-age
      adults with Huntington's disease (HD) are unknown. This study developed and
      tested psychometric properties of the Huntington Disease Family Concerns and
      Strategies Survey (HDFCSS). Focus group data from 91 adult family members were
      used to develop content. Content analysis yielded four domains that were
      transferred into Personal, Person With HD, Community Health Care Services, and
      Strategies scales. Focus group data, expert validation, and cognitive interviews
      demonstrated survey content validity. Cronbach's alpha internal consistency
      coefficients for the scales were 0.83 or above. The measure can be used to
      generate reliable and valid data to identify adult family members' health-related
      concerns and management strategies for themselves and persons with HD.

PMID- 20806653
TI  - Factor analysis of the transcultural self-efficacy tool (TSET).
AB  - he factor structure of the Transcultural Self-Efficacy Tool (TSET) was analyzed
      using data from 272 culturally diverse undergraduate nursing students. The TSET
      is a questionnaire designed to measure students' confidence for performing
      general transcultural nursing skills among diverse client populations. Using the
      most recent imputation techniques for missing data, researchers demonstrate how
      common exploratory factor analysis (CEFA)--(as opposed to principal components
      analysis)--can (and should be) used in examining the factorial composition of the
      tool. Standard errors for factor loadings were computed and utilized in deciding
      whether a given item loaded significantly on a factor and whether the difference
      between the factor loadings of two or more items on the same factor were
      statistically significant. The CEFA, comprised of 69 of the 83 items, yielded
      four factors--"Knowledge and Understanding'," "Interview," "Awareness,
      Acceptance, and Appreciation," and "Recognition"--with internal consistency
      ranging from .94 to .98. Reliability of the total instrument was .99. It was
      concluded that the present CEFA study continues to support that the TSET assesses
      the multidimensional nature of transcultural self-efficacy while also
      differentiating between three types of learning: cognitive, practical, and
      affective. The benefits of this support allow the researcher/ educator to move
      beyond mere assessment to the design, implementation, and evaluation of
      diagnostic-prescriptive teaching strategies for cultural competence education.

PMID- 20806654
TI  - Hematologic and plasma biochemical reference values in Indian peafowl (Pavo
      cristatus).
AB  - Blood samples were collected from captive, adult, clinically normal Indian
      peafowl (Pavo cristatus) for hematologic and plasma biochemical analyses.
      Hematologic parameters investigated were total red blood cell count, hemoglobin,
      packed cell volume, fibrinogen, mean cell volume, mean cell hemoglobin, mean cell
      hemoglobin concentration, total white blood cell count, differential white blood
      cell count, and thrombocyte count. Plasma biochemical parameters investigated
      were alanine aminotransferase, alkaline phosphatase, amylase, aspartate
      aminotransferase, bile acids, total bilirubin, blood urea nitrogen, calcium,
      cholesterol, creatinine, creatine kinase, gamma glutamyltransferase, lactate
      dehydrogenase, glucose, iron, phosphorus, and uric acid, as well as plasma
      protein electrophoresis. Results were compared with values from studies done in
      houbara bustards (Chlamydotis undulata), kori bustards (Ardeotis kori), stone
      curlews (Burhinus oedicnemus), and taxonomically related species, including ring
      necked pheasants (Phasianus colchicus), red-legged partridges (Alectoris rufa),
      Kashmir native fowl (Kashmirfavorella), and Bangladesh native, Fayoumi, and Assil
      fowl (Gallus domesticus).

PMID- 20806655
TI  - Effect of a commercial paratyphus vaccine on the development of pigeon circovirus
      infection in young pigeons (Columba livia domestica).
AB  - Infection with pigeon circovirus (PiCV) has been associated with young pigeon
      disease syndrome (YPDS), which is considered to be a multifactorial disease. The
      factors that determine whether birds succumb to clinical disease are not known.
      To evaluate the potential effect of vaccination with a commercial paratyphus
      vaccine on the progression of PiCV infection in young pigeons, forty 6-week-old
      pigeons naturally infected with PiCV were randomly assigned to two equal groups.
      The pigeons of one group were vaccinated at 6 and 9 weeks of age, and pigeons of
      the second group were unvaccinated controls. Cloacal swab and blood samples
      collected from all the birds were tested for PiCV by polymerase chain reaction
      (PCR) analysis. Three weeks after the second vaccination, all pigeons were
      euthanatized, and tissues were collected for PiCV PCR analysis and
      histopathologic evaluation. No significant difference in the number of PCR
      positive cloacal swab and blood samples was found between the vaccinated and
      control pigeons. Positive PCR results in tissue samples also were not
      significantly different between the groups, with 18 positive samples in
      vaccinated birds (90%) and 16 in control birds (80%). Characteristic botryoid
      inclusions were detected in more vaccinated than control pigeons, but this
      difference was not significant. In this study, vaccination with a commercial
      paratyphus vaccine was not a risk factor for development of young pigeon disease
      syndrome.

PMID- 20806656
TI  - Relationship of hemoglobin concentration to packed cell volume in avian blood
      samples.
AB  - To determine whether a proportional relationship exists between hemoglobin (Hgb)
      concentration and pack cell volume (PCV) in avian blood samples, Hgb
      concentration measured by a point-of-care portable hemoglobinometer and
      corresponding PCV were determined in blood samples collected from 128 birds
      comprising 13 avian orders. For all birds evaluated and pooled across orders, a
      significant and consistent relationship was found between Hgb concentration and
      PCV, expressed as Hgb = 0.304 x PCV + 0.461. To determine whether the
      relationship of PCV and Hgb differs, 9 avian orders with n > or = 8 samples per
      order were analyzed by linear regression. Individual slopes for the 9 orders did
      not differ significantly (P = .44), indicating that a single slope can be used to
      model the avian Hgb to PCV relationship for these taxonomic orders. A single
      intercept can also be used, with the exception of order Phoenicopteriformes,
      which was the only intercept that was significantly different from 0 (P = .01).
      These results indicate that a simplified relationship of Hgb (g/dL) = 0.30 x PCV
      provides a reasonable estimate of Hgb concentration from the PCV of birds from
      the orders Anseriformes, Columbiformes, Falconiformes, Galliformes,
      Passeriformes, Psittaciformes, Sphenisciformes, and Strigiformes, but a separate
      relationship of Hgb = 0.217 x PCV + 6.69 might be warranted for the order
      Phoenicopteriformes.

PMID- 20806657
TI  - Pharmacokinetics of terbinafine after single oral dose administration in red
      tailed hawks (Buteo jamaicensis).
AB  - To determine pharmacokinetic parameters of orally administered terbinafine
      hydrochloride for potential treatment of aspergillosis in raptors, 10 adult red
      tailed hawks (Buteo jamaicensis) were used in single dose trials by using 15, 30,
      and 60 mg/kg doses with a 2-week washout period between trials. After
      administration of 15 mg/kg terbinafine, mean (+/- SD) plasma concentration peaked
      in approximately 5 hours at 0.3 +/- 0.24 microg/mL, whereas a 30 mg/kg dose
      resulted in peak mean (+/- SD) plasma concentration of 1.2 +/- 0.40 microg/mL in
      3 hours and a 60 mg/kg dose resulted in mean (+/- SD) concentration of 2.0 +/-
      0.75 microg/mL in 5 hours. The volume of distribution decreased with increasing
      doses, averaging 76.8 +/- 38.06 mL/kg for the 15 mg/kg dose and falling to 55.2
      +/- 17.4 mL/kg for the 30 mg/kg dose. This suggests that terbinafine accumulated
      in deep tissues, limiting further distribution at higher doses. The harmonic mean
      (+/- SD) half-life was biphasic, with initial values of 14.7 +/- 6.67 hours, 17.5
      +/- 8.7 hours, and 13.3 +/- 5.03 hours for 15, 30, and 60 mg/kg doses,
      respectively. A rapid first-elimination phase was followed by a slower second
      phase, and final elimination was estimated to be 161 +/- 78.2 and 147 +/- 65.6
      hours for 15 and 30 mg/kg doses, respectively. Linearity was demonstrated for the
      area under the curve but not for peak plasma concentrations for the 3 doses used.
      Calculations based on pharmacokinetic parameter values indicated that a dosage of
      22 mg/kg terbinafine q24h would result in steady-state trough plasma
      concentrations above the minimum inhibitory concentration of terbinafine (0.8-1.6
      microg/mL). This dosage is recommended as a potential treatment option for
      aspergillosis in raptors. However, additional research is required to determine
      both treatment efficacy and safety.

PMID- 20806658
TI  - Selected complete blood cell count and plasma protein electrophoresis parameters
      in pet psittacine birds evaluated for illness.
AB  - Veterinarians rely on results of both the complete blood cell count (CBC) and
      plasma protein electrophoresis (EPH) in conjunction with the results of the
      plasma biochemical analysis to evaluate the health status of avian patients.
      Because the CBC and protein EPH measure different aspects of the immune response
      to disease, both tests are recommended in avian patients to rule out infectious
      or inflammatory disease. To evaluate results of the CBC and protein EPH in pet
      psittacine birds, the records of 144 pet psittacine birds, comprising 11 genera,
      that were presented for suspected illness were reviewed. Results of the CBC
      (total white blood cell count and packed cell volume) and protein EPH (alpha,
      beta, and gamma globulin concentrations) from submitted blood samples from each
      bird were evaluated. Of the 144 birds, 63 (43.8%) had abnormal CBC results, and
      25 (17.4%) had abnormal EPH measurements. Results of the CBC and protein EPH were
      within reference ranges in 73 birds (50.7%). Abnormal results of the CBC in
      conjunction with normal EPH results were present in 46 birds (31.9%), compared
      with 8 birds (5.6%) with normal results of the CBC and abnormal EPH results. The
      findings of this study could aid practitioners in evaluating psittacine patients
      and prioritizing the value of individual diagnostic tests.

PMID- 20806659
TI  - Intraocular pressure in captive black-footed penguins (Spheniscus demevsus)
      measured by rebound tonometry.
AB  - Intraocular pressure (IOP) measurement is a common procedure during eye
      examinations in birds. Differences in the IOP between avian species have been
      reported, which suggests the need to establish species-specific reference ranges.
      To determine IOP values of captive black-footed penguins (Spheniscus demersus),
      we obtained IOP readings with the use of a rebound tonometer by using two
      established calibration settings (dog and horse). No difference was seen in the
      IOP between the left and right eye when the horse setting was used; however, a
      difference was present when using the dog setting. No significant difference
      between the IOP of male and female penguins was seen in both eyes when the dog or
      horse setting was used. Rebound tonometry appears to be a safe and repeatable
      method to obtain IOP values in black-footed penguins.

PMID- 20806661
TI  - Practice pearls of wisdom.

PMID- 20806660
TI  - Cloacolith in a blue-fronted amazon parrot (Amazona aestiva).
AB  - A 4-year-old blue-fronted Amazon parrot (Amazona aestiva) was admitted for
      vocalization secondary to constipation. Saline infusion cloacoscopy revealed the
      presence of a 2-cm-diameter cloacolith within the coprodeum that was obstructing
      the rectal opening. The cloacolith was fragmented with a pair of biopsy forceps
      and the pieces removed. The cloacolith was subsequently analyzed and was composed
      of 100% uric acid salts. The bird improved completely and was able to defecate
      normally after the procedure. Cloacoliths are relative uncommon cloacal
      conditions, and this case documents cloacoscopic findings, rectal obstruction,
      and confirmation of its uric acid composition by urolith analysis.

PMID- 20806662
TI  - What is your diagnosis? Proventricular dilatation disease.

PMID- 20806663
TI  - Reflections on the culture of caring communities.

PMID- 20806665
TI  - Meeting needs of cancer survivors through holistic community programs.

PMID- 20806664
TI  - A day in my life: community health at the end of the line.

PMID- 20806666
TI  - The spiritual dimension of holistic care.

PMID- 20806667
TI  - Intentionally nursing the world to peace and healing: become the change you
      believe.

PMID- 20806668
TI  - AHNA: building a community to advance holistic health and nursing.

PMID- 20806670
TI  - Campus as community: health care for university students and staff.

PMID- 20806669
TI  - Food choices and medications in older adults.

PMID- 20806671
TI  - Nursing in the community: living a transforming dream.

PMID- 20806672
TI  - Spiritual energy healing in the UK.

PMID- 20806673
TI  - [Grading the level of suspicion in criminal proceedings, restrictions of the
      proportionality principle and veto options in forensic autopsies].
AB  - The article deals with two topics: determination of the necessary level of
      suspicion for an internal post-mortem examination pursuant to Section 87 (German)
      Code of Criminal Procedure and options of the family to object to the forensic
      autopsy. The level of suspicion required in this case is to be regarded as very
      low, even below that of the initial suspicion, because a detailed opinion as to
      any third-party fault can only be given after completion of the autopsy. The
      individual concerned does not have a right to oppose a forensic autopsy while
      still alive. The same applies to the family. Other than in clinical autopsies,
      the interest in prosecution is to be considered the higher good to be protected,
      because at the time of deciding a homicide cannot be ruled out and only an
      internal examination can furnish the necessary evidence. Consequently, it is
      appropriate. Contrary to the opinion often expressed in the literature, one
      cannot infer from the provisions of Sections 87 subs. 4, 33 subs. 3 Code of
      Criminal Procedure and Section 103 subs. 3 Basic Law that the family of the
      deceased has a right to be informed or heard. This can only be changed by the
      legislator in an amendment to the autopsy law.

PMID- 20806674
TI  - [Medicolegal identification of victims in mass disasters using the example of
      aircraft accidents].
AB  - In mass disasters, the main task of the medicolegal expert is to support the
      victims' identification. As such events are rare, the knowledge obtained during
      previous operations should be evaluated and published to improve the quality and
      effectiveness of the identification work in future disasters. This report
      describes the experience gained at the Institute of Forensic Medicine of the
      Humboldt University in Berlin during the identification of the victims of three
      aircraft accidents (1972, 1986, 1989). The advantages and disadvantages of the
      identification methods used are discussed. Medicolegal experts should make
      themselves familiar with available experiences to be adequately prepared for the
      responsible task of identifying the victims in an emergency.

PMID- 20806675
TI  - [Determining the postmortem interval of bone samples: a comparison of luminol
      chemiluminescence, Hexagon OBTI test, and Combur test].
AB  - In the experiment, 16 human bones with known postmortem interval (PMI) that had
      been buried in soil (0.2 to about 2000 years) were tested in a blind setup with
      two established methods for determining the PMI (UV fluorescence of the surface
      of a fresh cut and the luminol chemiluminescence) and with two methods applied
      for this purpose for the first time (Hexagon OBTI test and Combur test). The
      results underline the importance of the UV fluorescence and luminol tests in
      determining the PMI, especially with regard to the question whether the PMI is
      forensically relevant or not. The results for both new methods, the Combur test
      strips and the Hexagon OBTI test, which were originally developed for the
      detection of hemoglobin, were negative for all samples. It remains to be seen if
      the negative results for these two methods may be due to an inability of
      hemoglobin or its metabolites to dissolve in the Tris buffer solution used in the
      experiment.

PMID- 20806677
TI  - [Sudden/unexpected death due to spontaneous aortic rupture: two unusual
      manifestation forms].
AB  - Sudden unexpected death from a natural (pathological) cause often occurs under
      suspicious circumstances suggesting foreign intervention, so that a forensic
      autopsy is deemed necessary. In adults, a significant share of these deaths is
      due to spontaneous ruptures of the aorta. In figures, dissections of the
      ascending aorta and the aortic arch (mostly associated with secondary perforation
      into the pericardium) account for a large percentage followed by arteriosclerotic
      aneurysms of the abdominal aorta (with retroperitoneal and sometimes
      intraperitoneal hemorrhage). The authors report on two fatal aortic ruptures in
      which the hemorrhage showed an unusual route to spread. In the first case an 80
      year-old man with an arteriosclerotic aneurysm of the abdominal aorta died from
      acute intestinal bleeding via an aortojejunal fistula. In a 42-year-old man, a
      dissecting hemorrhage in the wall of the aortic arch resulted in the compression
      of the branching sites of the brachiocephalic trunk, the left common carotid
      artery and the left subclavian artery, while the volume of blood in the
      pericardium was rather small (60 ml). On the basis of these examples, the
      medicolegal aspects of spontaneous aortic ruptures are discussed.

PMID- 20806676
TI  - [Fatal sodium chloride intoxication--case report and review of the literature].
AB  - The authors describe the case of a 63-year-old, female nursing home inhabitant
      suffering from trisomy 21, who accidentally ingested the anti-epileptic
      medication of another nursing home inhabitant. After telephone instructions from
      a specialist in internal medicine, caregivers forced the woman to vomit by means
      of saline solution and digital manipulation. This caused not only substantial
      hypernatriaemia but also aspiration pneumonia, from which the woman died after
      short hospitalization. The potential toxicity by major electrolyte shifts in
      terms of hypernatriaemia following administration of sodium chloride solution is
      well known; this measure is medically contraindicated for the induction of
      vomiting. The mechanisms leading to death in this case are presented,
      differentiated and discussed against the background of the literature.

PMID- 20806678
TI  - Primary care clinicians' knowledge and confidence about newborn screening for
      sickle cell disease: randomized assessment of educational strategies.
AB  - OBJECTIVE: In Massachusetts, primary care clinicians receive and act upon
      hemoglobinopathy newborn screening results. We assessed clinicians' knowledge,
      confidence, and practices regarding hemoglobinopathy newborn screening, and the
      effect of mailed educational materials vs interactive seminar on knowledge and
      confidence. METHODS: A randomized educational intervention trial was performed at
      15 community health sites. Practices were randomized to determine the order in
      which the educational interventions were administered: mailed educational
      materials first or interactive seminars on the management of hemoglobinopathy
      newborn screening results first. Clinicians' demographics, knowledge, confidence,
      and practices were assessed by a survey. Posttests were administered soon after
      the intervention. RESULTS: Responses came from 85 of 170 eligible providers
      (50%). Twenty-nine percent of respondents provided both pretests and posttests.
      In respondents with paired data, knowledge on a 5-point scale improved by 1.4 +/-
      0.4 (mean +/- standard error of the mean, p = .003), while self-efficacy on a 16
      point scale increased by 1.3 +/- 0.3, p = .002. There were no significant
      differences between seminar and mailed-materials groups. CONCLUSIONS: Both
      educational strategies led to modest improvements in knowledge about newborn
      screening for hemoglobin disorders. Enhancing knowledge and confidence about
      newborn screening-related tasks may improve clinicians' capacity to act upon
      newborn screening results for hemoglobinopathies.

PMID- 20806679
TI  - A review of the evidence for disparities in child vs adult health care: a
      disparity in disparities.
AB  - Racial and ethnic health disparities in primary care have been well documented in
      the US healthcare system. However, very little attention has been directed toward
      inequities in child health. The aim of this review is to provide context for the
      scope of the challenges associated with addressing pediatric health disparities
      in primary care by comparing the weight of evidence regarding racial/ethnic
      health disparities for children vs adults. A multisystem health disparities
      conceptual model will frame the search strategy and analysis of the review. This
      paper will: (1) identify knowledge deficits in the understanding of existing
      disparities in pediatric primary care relative to adult primary care; (2) assess
      root causes of disparities for children vs adults; and (3) propose
      recommendations for a research agenda and policy implementation to eliminate
      disparities in pediatric primary care.

PMID- 20806680
TI  - Pediatric trauma at an adult trauma center.
AB  - BACKGROUND: Accidental traumatic injury is the number 1 cause of morbidity and
      mortality in the pediatric population. In this study, we aim to prove that
      certain pediatric patients can be treated with good outcomes at an adult level 1
      trauma center. METHODS: Retrospective analysis using the Howard University
      Hospital trauma registry identified 71 patients treated at Howard University
      Hospital between the ages of 1 and 17 years old. Specific variables were
      identified and collected for each patient. RESULTS: The majority of pediatric
      traumas treated at Howard University Hospital between June 2004 and May 2005 had
      high survival rates (93%). The patients who did not survive (7%) included 3
      patients who were dead on arrival and 2 who died shortly after arrival to the
      hospital. CONCLUSIONS: Certain pediatric populations who present with minor
      and/or isolated injuries can be treated in an adult level 1 trauma center with
      similar outcomes to treatment in a pediatric level 1 trauma center.

PMID- 20806681
TI  - Pediatric folk beliefs of inner-city black Chicagoans.
AB  - OBJECTIVES: To estimate the familiarity of black inner-city Chicagoans with
      pediatric folk beliefs identified by key informants. STUDY DESIGN: Five black
      staff members at an inner-city clinic identified 10 African American folk beliefs
      regarding pediatric care. A survey of 606 African American patients in Chicago
      assessed familiarity with these beliefs, and with medical recommendations
      regarding immunization and sleep position. RESULTS: The 2 medical recommendations
      were more familiar and more believed than any of the identified folk beliefs. The
      most widely known folk belief was that it is dangerous for a woman to go outdoors
      4 to 6 weeks after she has a baby, which was familiar to 93% of respondents. The
      most believed cultural item was that it is bad to stand where an infant has to
      roll his eyes back to see you, which was familiar to 86% of respondents and
      thought true by 86% of those familiar with it. Respondents born in a southern
      state were significantly more likely to have heard of taping a coin over an
      umbilicus that sticks out (odds ratio [OR], 1.51; 95% confidence interval [Cl],
      1.01-2.26; p = .045) and less likely to agree with infant back or side position
      for sleep (OR, 0.35; 95% CI, 0.14-0.85; p = .021). CONCLUSION: The widespread
      familiarity with specific folk beliefs in this population suggests that an
      understanding of these beliefs may be important for culturally competent
      providers of pediatric care in Chicago's inner city. Further research is needed
      to determine whether these findings are reproducible in other socioeconomic and
      geographic settings.

PMID- 20806682
TI  - Aggregate cardiovascular risk is a stronger statistical correlate of clinically
      evident diabetic peripheral neuropathy than HbA1c alone.
AB  - BACKGROUND: Apart from chronic hyperglycemia measured by hemoglobin A1c (HbA1c),
      other vascular risk factors contribute to the development of diabetic neuropathy.
      Even though these factors are synergistic, no study has measured the relative
      effect of aggregate cardiovascular risk load compared with chronic hyperglycemia
      alone on the risk of clinically evident diabetic peripheral neuropathy.
      OBJECTIVE: To compare the effects of aggregate cardiovascular risk load and HbA1c
      on clinically evident diabetic peripheral neuropathy. METHODS: We studied 277
      consecutive and consenting type 2 diabetic outpatients attending the University
      College Hospital, Ibadan, Nigeria. Neuropathy was defined operationally as at
      least 7 positive responses on the Michigan Neuropathy Screening Instrument (MNSI)
      questionnaire or a score greater than 2.0 on the MNSI examination: thresholds
      defined by prior validation studies. Patients with nondiabetic causes of
      neuropathy were excluded. We determined the HbA1c using the ionic exchange
      chromatographic method and later computed the Diabetes Control Complications
      Trial referenced values. Aggregate cardiovascular risk load was determined using
      the UK Prospective Diabetes Study risk engines. RESULTS: One hundred ninety-seven
      (71.1%) patients had clinically evident diabetic peripheral neuropathy. The mean
      HbA1c value was 6.9%. HbA1c correlated significantly with the average fasting
      plasma glucose (r = 0.36) but did not correlate significantly with the
      development of clinically evident diabetic peripheral neuropathy (p = .465, p = 
      0.045). Aggregate cardiovascular risk load had the strongest significant
      correlation with clinically evident diabetic peripheral neuropathy (p = .002, p =
      0.186, odds ratio, 2.3 for score > 5). In the regression analysis, aggregate
      cardiovascular risk load was a stronger predictor of clinically evident diabetic
      peripheral neuropathy than HbA1c. CONCLUSIONS: Aggregate cardiovascular risk load
      was a stronger statistical correlate and predictor of clinically evident diabetic
      peripheral neuropathy than HbA1c. This may have implications for prevention and
      monitoring of clinically evident diabetic peripheral neuropathy.

PMID- 20806684
TI  - Crossing the finish line: follow-up of abnormal test results in a multisite
      community health center.
AB  - BACKGROUND: Inadequate follow-up of abnormal test results is a common safety
      problem in outpatient practice. However, it is unclear exactly where and how
      often failures occur in the results management process. Our goal was to determine
      where breakdowns occur by examining 4 high-risk abnormal test results in a group
      of 11 clinics of an urban community health center organization. METHODS: Using a
      chart audit, we counted failures in the management of abnormal results of 4
      tests: Pap smears, mammograms, international normalized ratio (INR), and prostate
      specific antigen (PSA). We assessed documentation that the result was filed in
      the chart; the provider signed and responded to the result; the patient was
      notified of the result; the appropriate follow-up occurred, and it occurred in a
      timely manner or there was explicit patient refusal of the recommended follow-up.
      RESULTS: There were 344 abnormal test results (105 Pap smears, 82 mammograms, 61
      INRs, and 96 PSAs). The highest rate of failures in the management process was at
      follow-up care; 34% of the abnormal results did not have documentation that
      appropriate follow-up had occurred (11% for mammography, 26% for INR, 45% for Pap
      smears, and 46% for PSA). All of the earlier steps were performed with far fewer
      failures. For patients receiving follow-up care, 49% of the time, follow-up care
      did not occur in a timely manner. CONCLUSIONS: Most breakdowns in the testing
      process for these 4 abnormal tests were in the final step, documenting that
      appropriate follow-up care occurred. Office systems for managing abnormal results
      reporting and patient follow-up are needed to improve the safety and quality of
      care.

PMID- 20806683
TI  - Care of the underserved: faculty development needs assessment.
AB  - INTRODUCTION: Because role models are crucial to training physicians to care for
      the underserved, we examined pediatric faculty's knowledge, attitudes, self
      efficacy, skills, and precepting behaviors regarding care for this population.
      METHODS: Faculty knowledge, attitudes, self-efficacy, and skills/precepting
      behaviors were surveyed. RESULTS: Fifty-five (65%) of 85 faculty responded. The
      mean (standard deviation) knowledge score was 5.9 (1.3) of 8 possible. More than
      one-third of faculty did not recognize the eligibility criteria, services, and
      outcomes associated with common resources serving the underserved. Overall
      attitudes toward underserved families were positive, mean 3.3 (0.3), as was mean
      self-efficacy, 3.0 (0.7). Self-efficacy was lowest for accessing community
      resources for underserved families, 2.4 (0.7). Although most faculty performed
      the surveyed skills, fewer than 50% reported, precepting of these same skills
      with students. Precepting was lowest for accessing public and community
      resources. CONCLUSIONS: Low rates of student precepting as well as specific
      knowledge and self-efficacy deficits highlight potential targets for faculty
      development.

PMID- 20806685
TI  - The relationship between mean platelet volume levels and the inflammation in
      Helicobacter pylori gastritis.
AB  - Helicobacter pylori is a cause of chronic gastritis. Mean platelet volume (MPV)
      has been started to be used as a simple inflammatory indicator in some diseases.
      We have aimed especially to investigate the usability of MPV as a simple
      indicator that may reflect severity of inflammation in gastric mucosa. Included
      in the study were a total of 114 patients who visited the outpatient clinic of
      gastroenterology with complaint of dyspepsia. Blood MPV levels in hemogram
      results were evaluated. Esophagogastroduodenoscopy was performed on patients
      included in the study, and histological analysis was performed by obtaining 2
      specimens from each of antrum, corpus, and incisura angularis. All specimens were
      evaluated according to the updated Sydney System. No statistically significant
      result was found among blood MPV levels, the intensity of H pylori, and the
      severity of inflammation of gastric mucosa. However, it is interesting that mean
      MPV levels in cases with lymphoid follicle were lower. We suggest that MPV level
      cannot be used as a simple marker to reflect H pylori intensity and severity of
      inflammation in gastric endoscopic biopsies.

PMID- 20806686
TI  - Incarcerated Spigelian hernia: a rare cause of mechanical small-bowel
      obstruction.
AB  - Spigelian hernias are rare abdominal wall defects that occur at the semilunar
      line lateral to the rectus abdominis muscle. The majority of patients present
      with symptomatic incarceration of preperitoneal fat or intra-abdominal viscera.
      Radiographic studies are beneficial in confirming the diagnosis. The high rate of
      incarceration with or without strangulation mandates operative repair once the
      diagnosis is confirmed. This manuscript outlines the clinical presentation and
      management of a patient with an incarcerated Spigelian hernia.

PMID- 20806687
TI  - The Journal of the National Medical Association 100 years ago: a new voice of and
      for African American physicians.
AB  - Volume 1 of the Journal of the National Medical Association (JNMA), published
      quarterly during 1909, included a good deal of space devoted to 2 key concerns:
      (1) building and unifying black health professionals in medicine, surgery,
      dentistry, and pharmacy; and (2) providing a voice for these African American
      health professionals to the often-hostile and racist larger world of medicine.
      The Journal's editor, Charles Victor Roman, and associate editor, John A. Kenney,
      were well suited to the task. They promoted membership in the National Medical
      Association (NMA), attendance at NMA annual meetings, and cooperation among the
      health professions. They also used the pages of the JNMA to firmly respond to the
      negative articles and biased, even hateful, attitudes expressed by white medical
      and lay people. The JNMA has continued to speak for the black medical profession
      over the subsequent 100 years.

PMID- 20806688
TI  - Privacy (or piracy) or medical records: HIPAA and its enforcement.

PMID- 20806689
TI  - The shadow of your smile.

PMID- 20806690
TI  - More strides made in detecting oral cancer using nano biochips.

PMID- 20806691
TI  - Improving from within.

PMID- 20806692
TI  - Reface, remodel, or rebuild your dental office.
AB  - Upgrades to a dental practice can range from a minor facelift to all new
      construction. Consulting a certified public accountant is important to properly
      account for all the various assets that go into a new office so the tax benefits
      from each can be optimized. After all the dust has settled, practitioners will be
      able to take pride in their new dental facility and enjoy their surroundings for
      many years to come.

PMID- 20806693
TI  - Maximizing practice management in the newly remodeled practice.
AB  - Embarking on the building of a new facility, or remodeling an existing space, can
      be an exciting time. In the midst of planning and decision-making, do not
      overlook two groups of people who represent driving forces behind the overall
      success of this investment--patients and staff. In rejuvenating a facility, it is
      important to remember that at every level, patients' needs must be taken into
      consideration, including a fundamental review--and potential "overhaul"--of
      internal systems.

PMID- 20806694
TI  - Effect of axial height and palatal wall on the resistance form of a maxillary
      anterior metal-ceramic crown preparation.
AB  - The effect of palatal wall modifications and height of a maxillary central
      incisor on the resistance form of metal-ceramic crowns are compared. Dies with
      adequate preparation height show no crown dislodgement in groups with a palatal
      wall, palatal wall/groove, and no palatal wall. This study suggests the use of a
      palatal groove improves the resistance to dislodgement in short maxillary
      anterior tooth preparations.

PMID- 20806695
TI  - Foreign body in the mouth and the dilemma in diagnosis: a case report.
AB  - Foreign bodies impaled or stuck in the oral cavity have been reported in
      literature. The purpose of this case report is to document an embedded foreign
      object in the maxillary tuberosity region of a 6-month-old baby, mimicking
      features of a tumor leading to a diagnostic dilemma. This report cautions the
      clinician faced with diagnosis of tumor in infants to consider the possibility of
      a foreign body.

PMID- 20806696
TI  - Crazy for chicle.

PMID- 20806697
TI  - Calls to action.

PMID- 20806698
TI  - Options are good in the health insurance marketplace.

PMID- 20806699
TI  - Developing treatment algorithms for restoration or replacement of the compromised
      tooth.

PMID- 20806701
TI  - A century of endodontics: from Philadelphia to Boston.
AB  - While Dr. Grossman was in Rostock with a letter of introduction from Dr. Prinz,
      he visited several distinguished dentists in Berlin. One was the aged Dr. Otto
      Walkoff, who, with the help of a physicist while in Wurzberg, was the first
      dentist to capture the image of a tooth soon after the discovery of radiology by
      Roentgen in 1895. At his home, Dr. Walkoff passed the X-ray tube head that had
      taken the historic film to Dr. Grossman, who then held this treasured artifact in
      his hands. This transfer of culture from Germany to the United States marked the
      beginning of modern endodontics. Similarly, when Dr. Goldman gave Dr. Schilder
      his backing by sending him to study under Dr. Grossman at the University of
      Pennsylvania, the progress of endodontic excellence moved forward, ensuring a
      Century of Endodontics.

PMID- 20806700
TI  - Methemoglobinemia and local anesthesia: what every dentist should know.

PMID- 20806702
TI  - Going...going...going...gone green. Making your dental practice environmentally
      friendly.

PMID- 20806703
TI  - Bacterial microleakage and post space timing for two endodontic sealers: an in
      vitro study.
AB  - AIM: The effects of immediate versus delayed post space preparation on the apical
      seal using resin and zinc oxide eugenol (ZOE) sealers were compared by a
      bacterial leakage model. METHODOLOGY: Eighty-six premolars were randomly assigned
      to four experimental groups of 20 teeth. Three teeth were assigned to each
      control group, either positive (filled only with guttapercha) or negative (not
      obturated but root surfaces completely covered). Obturation was achieved by gutta
      percha with resin or gutta-percha with a ZOE sealer and lateral condensation
      technique. Post space was prepared either immediately or a week later, while the
      obturated teeth had been stored in 100 percent relative humidity at 37 degrees C.
      The teeth were inserted into plastic vials and suspended in glass bottles. All
      teeth were covered with cyanoacrylate and layers of nail varnish but the apical 3
      mm and were sterilized using gamma rays. Phenol red lactose broth was inoculated
      into the vials. Staphylococcus epidermidis was introduced into the root canal
      access of the teeth. Turbidity of the broth in the vials (discoloration) was
      evaluated daily for a period of 70 days. The data was analyzed statistically with
      Pearson Chi Square and two ways with ANOVA at 45 days and 70 days. RESULTS: When
      the depth of time was considered, the mean time of leakage showed no differences
      between immediate and delayed preparation for resin AH26 versus ZOE Dorifil at 45
      and 70 days (p = 0.37 and p = 0.217, respectively). In 45 days, considering the
      number of teeth with leakage, there was a significant difference between
      immediate preparation and delayed preparation in AH26 sealer groups (p = 0.028).
      No difference was present between immediate and delayed preparation groups for
      the ZOE sealer groups (p = 0.14). CONCLUSION: According to the results of this
      study and despite type of sealer, immediate post space preparation did not
      achieve better sealing than delayed post space preparation. Resin AH26 showed the
      least leaking teeth in 45 days, but it made no difference in 70 days.

PMID- 20806704
TI  - A 50-year journey from Begg to straight wire and beyond: is orthodontics on the
      correct course today?

PMID- 20806705
TI  - Dental erosion.

PMID- 20806706
TI  - A clinico-pathologic correlation. Odontogenic myxoma.

PMID- 20806707
TI  - Multidisciplinary occlusal restoration.

PMID- 20806708
TI  - If you can't say something nice...

PMID- 20806709
TI  - Points of Light: a win-win program.

PMID- 20806710
TI  - Prescribe pain medication only to patients of record.

PMID- 20806711
TI  - An extramarital affair is destroying my office.

PMID- 20806712
TI  - Publishing of disciplinary reports in the MDA Journal.

PMID- 20806713
TI  - Look to MDA insurance for your health care needs.

PMID- 20806714
TI  - Try this new approach to sick days.

PMID- 20806715
TI  - A new trustee's perspective on the ADA.

PMID- 20806716
TI  - The MDA: helping member dentists succeed.

PMID- 20806717
TI  - Improving access in the U.P.: the care free dental clinic.

PMID- 20806718
TI  - Oral pathology quiz #22. Static bone cavity.

PMID- 20806719
TI  - A computational model for cortical endosteal surface remodeling induced by
      mechanical disuse.
AB  - In mechanical disuse conditions associated with immobilization and microgravity
      in spaceflight, cortical endosteal surface moved outward with periosteal surface
      moving slightly or unchanged, resulting in reduction of cortical thickness.
      Reduced thickness of the shaft cortex of long bone can be considered as an
      independent predictor of fractures. Accordingly, it is important to study the
      remodeling process at cortical endosteal surface. This paper presents a computer
      simulation of cortical endosteal remodeling induced by mechanical disuse at the
      Basic Multicellular Units level with cortical thickness as controlling variables.
      The remodeling analysis was performed on a representative rectangular slice of
      the cross section of cortical bone volume. The pQCT data showing the relationship
      between the duration of paralysis and bone structure of spinal cord injured
      patients by Eser et al. (2004) were used as an example of mechanical disuse to
      validate the model. Cortical thickness, BMU activation frequency, mechanical load
      and principal compressive strain for tibia and femur cortical models were
      simulated. The effects of varying the mechanical load and maximum BMU activation
      frequency were also investigated. The cortical thicknesses of femur and tibia
      models were both consistent with the clinical data. Varying the decreasing
      coefficient in mechanical load equation had little effect on the steady state
      values of cortical thickness and BMU activation frequency. However, it had much
      effect on the time to reach steady state. The maximum BMU activation frequency
      had effects on both the steady state value and the time to reach steady state for
      cortical thickness and BMU activation frequency. The computational model for
      cortical endosteal surface remodeling developed in this paper can be further used
      to quantify and predict the effects of mechanical factors and biological factors
      on cortical thickness and help us to better understand the relationship between
      bone morphology and mechanical as well as biological environment.

PMID- 20806720
TI  - Interactions between nearest-neighboring glycosaminoglycan molecules of articular
      cartilage.
AB  - The electrostatic interaction effects including the interaction potential, force
      and torque between the neighboring chondroitin sulfate glycosaminoglycan (CS-GAG)
      molecular chains in the bottle brush conformation of proteoglycan aggrecan are
      obtained as the functions of the minimum separation distance and the mutual angle
      between the molecular chains based on an asymptotic solution of the Poisson
      Boltzmann equation that the CS-GAGs satisfy under the normal physiological
      conditions of articular cartilage. The present study indicates that the
      electrostatic interactions are not only associated intimately with the separation
      distance and the mutual angle, which are shown as purely exponential in
      separation distance and decrease with increasing mutual angle, but also dependent
      sensitively on the saline concentration in the electrolyte solution within the
      tissue. Further analysis shows that in the range of the separation distance
      between two neighboring CS-GAG molecular chains in the bottle brush conformation
      of the aggrecan in vivo (2 to approximately 4 nm), if the saline concentration in
      the electrolyte solution is not less than a value of concentration (approximately
      0.1 M), the interactions between the molecular chains will monotonically increase
      with decreasing the saline concentration, however, if the saline concentration is
      less than the value of concentration, the relationship between the interactions
      and the saline concentration will not be simply monotonic. Some present results
      are in agreement with the existed relevant conclusions.

PMID- 20806721
TI  - On the mechanics of single sarcomeres.

PMID- 20806722
TI  - Structural basis of stress concentration in the cytoskeleton.
AB  - Professor Y.C. Fung has shown that living tissues remodel extensively in response
      to mechanical forces such as blood pressure variations. At the cellular level,
      those mechanical perturbations must be perceived by individual cells. However,
      mechanisms of mechanochemical transduction in living cells remain a central
      challenge to cell biologists. Contrary to predictions by existing models of
      living cells, we reported previously that a local stress, applied via integrin
      receptors, is propagated to remote sites in the cytoplasm and is concentrated at
      discrete foci. Here we report that these foci of strains and stresses in the
      cytoplasm correspond to local peak deformation or local buckling of microtubules
      and are near the actin bundles of the cell. Multiple images at different z
      heights demonstrated more foci of concentrated displacements in the middle of the
      cell than at the apex or at the cell base. Together with previously published
      work, these findings underscore the importance of tensed bundled filamentous
      actin in intracellular mechanical stress distribution and signaling.

PMID- 20806723
TI  - Changes in triphasic mechanical properties of proteoglycan-depleted articular
      cartilage extracted from osmotic swelling behavior monitored using high-frequency
      ultrasound.
AB  - This study aims to obtain osmosis-induced swelling strains of normal and
      proteoglycan (PG) depleted articular cartilage using an ultrasound system and to
      investigate the changes in its mechanical properties due to the PG depletion
      using a layered triphasic model. The swelling strains of 20 cylindrical cartilage
      bone samples collected from different bovine patellae were induced by decreasing
      the concentration of bath saline and monitored by the ultrasound system. The
      samples were subsequently digested by a trypsin solution for approximately 20 min
      to deplete proteoglycans, and the swelling behaviors of the digested samples were
      measured again. The bi-layered triphasic model proposed in our previous study
      (Wang et al., J Biomech Eng-Trans ASME 2007; 129: 413-422) was used to predict
      the layered aggregate modulus Ha from the data of depth-dependent swelling
      strain, fixed charge density and water content. It was found that the region near
      the bone, for the normal specimens, had a significantly higher aggregate modulus
      (Ha1 = 20.6 +/- 18.2 MPa) in comparison with the middle zone and the surface
      layer (Ha2 = 7.8 +/- 14.5 MPa and Ha3 = 3.6 +/- 3.2 MPa, respectively) (p <
      0.001). The normalized thickness of the deep layer h1 was 0.68 +/- 0.20. After
      the trypsin digestion, the parametric values decreased to Ha1 = 13.6 +/- 9.6 MPa,
      Ha2 = 6.7 +/- 11.5 MPa, Ha3 = 2.7 +/- 3.2 MPa, and h1 = 0.57 +/- 0.28. Other
      models were also used to analyze data and the results were compared. This study
      showed that high-frequency ultrasound measurement combined with the triphasic
      modeling was capable of nondestructively quantifying the alterations in the
      layered mechanical properties of the proteoglycan-depleted articular cartilage.

PMID- 20806724
TI  - The nursing list. 5 tips for choosing the right advanced nursing degree program.

PMID- 20806725
TI  - Surviving and thriving in the workplace. Managing work and school.

PMID- 20806726
TI  - Lifelong learning: how different journeys can lead to a single goal.

PMID- 20806727
TI  - Issue: may a nurse select and administer over-the-counter (OTC) medication to
      another individual?

PMID- 20806728
TI  - Becoming mindful.

PMID- 20806729
TI  - Workplace wisdom. What the law says about meal and rest breaks.

PMID- 20806730
TI  - The Physical Therapy Board of Craniofacial & Cervical Therapeutics.

PMID- 20806731
TI  - WHY? that is the question.

PMID- 20806732
TI  - Dr. Melis' comments on Tecco, et al.'s article in the January 2010 issue of
      CRANIO.

PMID- 20806733
TI  - Treatment outcome in patients with TMD--a survey of 123 patients referred to
      specialist care.
AB  - Temporomandibular disorders (TMD) are a group of functional disorders of the
      masticatory system. Signs and symptoms of TMD are very common in different age
      groups in both genders. Treatment need varies greatly, ranging from 5 to 27% of
      the population. The treatment of TMD patients is generally initiated using
      reversible conservative methods and if necessary, irreversible and surgical
      methods are used. Altogether 123 patients (93 females, 30 males, mean age 39
      years, range 12 to 72 years) were referred to the Oral and Maxillofacial
      Department of Oulu University Hospital between the years 2005 and 2008. The
      treatment outcome was evaluated using the anamnestic and clinical dysfunction
      indices of Helkimo, before and after treatment. The results of the study showed
      that the outcome of the conservative treatment methods of TMD and of surgical
      treatment, if needed, was beneficial, with a subjectively and clinically
      statistically significant decrease in signs and symptoms.

PMID- 20806734
TI  - Hyaluronic acid in the treatment of TMJ disorders: a systematic review of the
      literature.
AB  - Hyaluronate acid (HA) injections are gaining attention as a treatment option to
      manage symptoms of temporomandibular joint (TMJ) disorders, but updated evidence
      based data on their effectiveness are actually lacking. The present paper aims to
      summarize and review systematically the clinical studies on the use of hyaluronic
      acid injections to treat TMJ disorders performed over the last decade. On
      November 9, 2009, a systematic search in the National Library of Medicine's
      PubMed (http://www.ncbi.nlm.nih.gov/pubmed) database was performed by means of a
      combined MeSH and word terms to identify all peer-reviewed papers published in
      the English literature dealing with the hyaluronic acid infiltration in patients
      affected by TMJ disorders. The selected papers were assessed according to a
      structured reading of articles format, which provided that the study design was
      methodologically evaluated in relation to four main issues, viz., population,
      intervention, comparison, and outcome. Nineteen (N=19) papers were selected for
      inclusion in the review, twelve (N=12) dealt with the use of hyaluronic acid in
      TMJ disk displacements and seven (N=7) dealt with inflammatory-degenerative
      disorders. Only nine groups of researchers were involved in the studies, and less
      than half of the studies (8/19) were randomized and controlled trials (RCTs). All
      studies reported a decrease in pain levels independently by the patients'
      disorder and by the adopted injection protocol. Positive outcomes were maintained
      over the follow-up period, which was varied among studies, ranging between 15
      days and 24 months. The superiority of HA injections was shown only against
      placebo saline injections, but outcomes are comparable with those achieved with
      corticosteroid injections or oral appliances. The available literature seems to
      be inconclusive as to the effectiveness of HA injections with respect to other
      therapeutic modalities in treating TMJ disorders. Studies with a better
      methodological design are needed to gain better insight into this issue and to
      draw clinically useful information on the most suitable protocols for each
      different TMJ disorder.

PMID- 20806735
TI  - Trigeminal impingement syndrome: the relationship between atypical trigeminal
      symptoms and anteromedial disk displacement.
AB  - The purpose of this study was to determine if compression of the mandibular nerve
      and its branches could be caused by antero-medial disk displacement, resulting in
      atypical facial pain. Sixteen temporomandibular joints (TMJ) were dissected and
      injected with an autopolymerizing solution into the superior compartment, which
      produced an artificial capsular swelling that caused disk displacement. In all
      specimens, the TMJ capsule was close to the mandibular branch of the trigeminal
      nerve after the intracapsular injection. Thus, capsular distension or antero
      medial disk displacement, as seen in various temporomandibular disorders (TMD),
      could result in nerve compression and facial pain symptoms.

PMID- 20806736
TI  - Evaluation of the stomatognathic system in patients with rheumatoid arthritis
      according to the research diagnostic criteria for temporomandibular disorders.
AB  - The aim of this study was to investigate the clinical features of stomatognathic
      dysfunction in patients with rheumatoid arthritis (RA). The study sample
      consisted of 40 patients with RA (34 female, 6 male), mean age 44 years,
      recruited at the Rheumatology Division of the Department of Internal Medicine,
      University of Pisa, Italy. The inclusion criteria were diagnosis of RA according
      to the criteria of the American Rheumatism Association (ARA). In the study, 82.5%
      (n=33) of patients affected by RA satisfied at least the criteria of one
      diagnosis of temporomandibular disorders (TMD), according to the Research
      Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). The results are in
      agreement with the literature and the prevalence of such involvement ranges
      between 53% and 94% of patients. Several studies reported an involvement of the
      stomatognathic system in RA. In fact, RA can affect the temporomandibular joint
      as much as any other synovial joint. A more thorough analysis is required for a
      multidisciplinary approach to gnathological patients, including assessment by a
      rheumatologist. This issue and its epidemiologic relevance need further
      scientific research. Dentistry has a fundamental role in this process since
      patients who present with a systemic disease such as RA can be recognized and
      intercepted and referred to medical specialists, i.e., rheumatologists, to
      provide a diagnosis and therapy.

PMID- 20806737
TI  - Effect of cigarette smoking on pain intensity of TMD patients: a pilot study.
AB  - To evaluate the effect of cigarette smoking (CS) on pain intensity in a sample of
      temporomandibular disorder (TMD) patients, 352 clinical charts were reviewed.
      Subjects were first divided into two groups: smokers (YS) and nonsmokers (NS);
      then, YS were further divided into three subgroups: light smokers (LS), moderate
      smokers (MS), and heavy smokers (HS). Overall TMD pain intensity was higher in
      YS, compared to NS, and a correlation was found between pain intensity and the
      number of cigarettes smoked in a day by each subject. A significant difference
      was evident between NS and HS. The results were not evident in males; age was not
      correlated either with smoking or pain intensity, and the effect of CS on pain
      intensity was not correlated with any particular TMD diagnosis. CS seems to be a
      relevant factor affecting the intensity of TMD pain, thus, control of smoking
      habits should be considered when treating TMD patients.

PMID- 20806738
TI  - Orthodontic treatment for the TMJ patient following splint therapy to stabilize a
      displaced disk(s): a systemized approach. Part I, TMJ orthodontic diagnosis.
AB  - Orthodontic treatment for a patient who has had a displaced disk or disks and has
      been stabilized by anterior repositioning splint therapy presents the dentist
      with a difficult orthodontic problem. Frequently, there is a posterior open bite
      present, with the anterior teeth only occluding in the stabilized TMJ position
      upon removal of the splint. The current articles (Part I of II presented here)
      will present an organized TMJ/orthodontic diagnosis (Part I) and orthodontic
      treatment method (Part II, to be presented in the next journal) to properly treat
      these patients to a consistent stabilized occlusion compatible with the TMJ
      splint stabilized position.

PMID- 20806739
TI  - The iatrogenic fracture of the coronoid process of the mandible. A review of the
      literature and case presentation.
AB  - An unusual case of an isolated fracture of the coronoid mandibular process is
      presented. The fracture was randomly discovered after a panoramic radiograph was
      taken for surgical purposes. There were no clinical findings or symptoms by the
      patient. A careful review of the literature of fractures of the coronoid process
      is presented, since the isolated coronoid fracture is the rarest occurrence of
      all facial fractures.

PMID- 20806740
TI  - Cerebellopontine angle (CPA) tumor mimicking dental pain following facial trauma.
AB  - Facial injuries are common during workplace accidents. These incidents are also
      associated with an increase in both mortality and morbidity rates. The following
      case describes a 40-year-old white Hispanic patient with paroxysmal facial pain
      on the right side, one year in duration. The patient reported facial trauma as a
      result of a direct fall thought to be related to his pain complaints five months
      prior to arriving at the New Jersey Dental School emergency unit. The facial pain
      was progressively worsening ever since the accident. Upon arrival at the
      emergency unit, a comprehensive intraoral and extraoral examination was
      performed. Application of a local anesthetic at the site of the pain produced
      equivocal results. After obtaining a complete history and clinical examination,
      an MRI was ordered to rule out the possibility of a space-occupying lesion in the
      brain considered as a possible source of the pain. This case focuses on different
      aspects relative to dental care: the importance of a complete history and patient
      evaluation in order to make an accurate diagnosis; the complexity of orofacial
      pain; and the training required for dental health care providers who treat
      unusual oral and facial pain complaints.

PMID- 20806741
TI  - Intraocular gas associated pressure-induced interface keratopathy 8 years after
      laser in situ keratomileusis.
AB  - The authors report a clinically distinctive form of elevated intraocular pressure
      induced interface keratopathy that occurred after a pars plana vitrectomy with
      intraocular gas tamponade for a macular hole in the right eye in a 35-year-old
      woman who had laser in situ keratomileusis in both eyes 8 years previously. The
      intraocular pressure was increased to 37 mm Hg after surgery. Diffuse lamellar
      keratitis-like interface infiltration was found with concurrent elevated
      intraocular pressure. The interface infiltration did not respond to steroids but
      resolved after the intraocular pressure was controlled. This case suggests that
      interface keratopathy is associated with increased intraocular pressure.
      Assessment of intraocular pressure is essential in patients presenting with
      interface keratopathy, especially in those who have undergone posterior segment
      operations with gas tamponade.

PMID- 20806742
TI  - Apoptosis in diabetic fibrovascular membranes after panretinal photocoagulation.
AB  - A more complete understanding of the role of apoptosis in the regression of
      diabetic neovasculature following laser panretinal photocoagulation (PRP) will
      both elucidate the treatment's therapeutic mechanism and potentially lead to
      novel treatments for neovascularization associated with proliferative diabetic
      retinopathy that target apoptotic pathways. Pars plana vitrectomy with
      fibrovascular membrane delamination was performed on five patients with
      proliferative diabetic retinopathy, with four having received previous PRP
      treatment and one no previous laser treatment. Using in situ terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling, propidium iodide
      and hematoxylin-eosin staining, apoptotic cells were identified in the excised
      membranes. The authors found evidence of cells undergoing apoptosis in all of the
      excised membranes, with increasing amounts of preoperative PRP associated with an
      increased number of apoptotic cells per millimeter of membrane. The preliminary
      data suggest that the decrease in ambient mitogen, initiated by PRP treatment,
      activates apoptosis in diabetic fibrovascular membranes.

PMID- 20806743
TI  - Acute postoperative endophthalmitis in a patient with Darier's disease.
AB  - A 58-year-old man with Darier's disease developed endophthalmitis 3 days
      following left-sided cataract extraction with intraocular lens implantation.
      Vitreous cultures were positive for Pseudomonas aeruginosa, similar to previously
      cultured hyperkeratotic plaques on the patient. Despite emergent vitrectomy and
      aggressive treatment with systemic, intravitreal, and topical fortified
      antibiotics, the patient required evisceration 19 days postoperatively. Bacterial
      overgrowth within hyperkeratotic plaques may increase the risk of endophthalmitis
      following intraocular surgery in patients with Darier's disease.

PMID- 20806744
TI  - Posterior segment ophthalmic complications of aplastic anemia.
AB  - Three patients with aplastic anemia were evaluated by the ophthalmology service
      within 2 months of the aplastic anemia diagnosis for bilateral visual loss. The
      mean age of diagnosis of aplastic anemia was 14.3 years (range: 5 to 19 years)
      and the mean follow-up was 25 months (range: 15 to 44 months). All 6 eyes
      demonstrated choroidal ischemia and vitreous hemorrhage. Pars plana vitrectomy
      was performed in four eyes of two patients for non-clearing vitreous hemorrhage;
      one patient was observed. Successful anatomic outcomes were achieved in 3 of 4
      eyes that underwent vitrectomy. Initial visual acuity ranged from 20/80 to bare
      light perception and final visual acuity ranged from 20/20 to no light
      perception. All patients received immunosuppressive therapy including
      cyclosporine and anti-thymocyte globulin, and two underwent hematopoietic stem
      cell transplantation. All patients received perioperative platelet and blood
      transfusions. Pars plana vitrectomy resulted in functional and anatomic success
      in the majority of eyes in this series. Coordination of medical and surgical care
      with the hematology service is advisable to stabilize hematologic parameters
      prior to undertaking a vitreoretinal procedure.

PMID- 20806745
TI  - Radiologic case study. Talocalcaneal coalition.

PMID- 20806746
TI  - The AAOS's Annual Meeting: A reflection of the academy?

PMID- 20806747
TI  - Total hip arthroplasty for fused hips.

PMID- 20806748
TI  - Meniscal tissue repair using radiofrequency.

PMID- 20806749
TI  - Good outcome after meniscal repair using an all-inside suturing system in
      combination with high-frequency biostimulation.

PMID- 20806750
TI  - Complications associated with treatment of malignancies: a focus on avascular
      necrosis of the bone.

PMID- 20806751
TI  - Scapulothoracic dissociation.

PMID- 20806752
TI  - Thoracolumbar burst fractures: a systematic review of management.
AB  - The management of thoracolumbar burst fractures remains challenging. Ideally, it
      should effectively correct the deformity, induce neurological recovery, allow
      early mobilization and return to work, and be associated with minimal risk of
      complication. This article reviews the related studies reporting their clinical
      data for the management of thoracolumbar burst fractures, discusses the most
      suitable approach in cases such as these, highlights specific treatment
      recommendations, and proposes a treatment algorithm. Using PubMed and Scopus
      databases to search the term thoracolumbar burst fractures, abstracts and
      original articles in English investigating the treatment of thoracolumbar burst
      fractures were searched and analyzed.

PMID- 20806753
TI  - Current concepts: neonatal brachial plexus palsy.

PMID- 20806755
TI  - Management of a massive stage IV sacral decubitus ulcer with anterior flap hip
      disarticulation and myocutaneous gastrocnemius fillet flap in-continuity.
AB  - Severe sacral decubitus ulcers represent a common and often recalcitrant clinical
      problem in paralyzed or bedridden patients and require treatment strategies
      ranging from specialty beds and local wound care to aggressive debridement and
      local or free tissue flap coverage. This article presents the case of a young
      soldier who sustained severe injuries as a result of an improvised explosive
      device blast, including bilateral sciatic nerve injuries, sacrogluteal degloving,
      and severe left acetabular and femoral head fractures. The patient subsequently
      developed a recalcitrant stage IV sacral decubitus ulcer, left acetabular
      protrusio with minimal left lower extremity function, and ankylosis of the
      posterior right hip due to heterotopic ossification. A novel left anterior
      (quadriceps-based) hip disarticulation was performed with a double gastrocnemius
      myocutaneous fillet flap in-continuity. The procedure was successful in providing
      robust, partially sensate soft tissue coverage for the decubitus ulcer,
      permitting removal of the bridging posterior heterotopic ossification of the
      right hip, and removing the left hip for which reconstructive options were
      limited due to the absence of superior and inferior gluteal nerve function. The
      patient healed uneventfully and was subsequently able to resume unrestricted
      positioning for sitting and wheelchair mobilization and became a limited
      ambulator with a hip disarticulation prosthesis and contralateral ankle-foot
      orthosis.

PMID- 20806756
TI  - Paraplegia caused by posture during MRI in a patient with cervical disk
      herniation.
AB  - A 48-year-old man presented with numbness in the lower left extremity of 4
      months' duration. One month earlier, he presented to an orthopedic clinic and
      magnetic resonance imaging (MRI) revealed cervical disk herniation. Because the
      pain did not subside, he visited the clinic again and MRI was performed. His neck
      was slightly extended and fixed to the headrest of the MRI instrument. Because of
      the posture of his cervical spine, he suffered severe pain in the scapular region
      during the MRI. After 15 minutes the pain was unbearable and the MRI examination
      was aborted. As the patient tried to descend from the MRI table, he was unable to
      move his bilateral lower extremities. No muscle contraction was observed in his
      lower limbs. Following MRI with flexion posture of the cervical spine, he was
      diagnosed with paraplegia caused by cervical disk herniation. Emergency surgery
      consisting of anterior decompression and fusion was performed. The patient showed
      good neurological recovery. Three weeks postoperatively, the patient could walk
      without assistance and he was discharged. The extension posture of the cervical
      spine during MRI was considered to be the cause of acute paraplegia in this
      patient. Care should be taken with the posture of the cervical spine, when
      performing MRI in patients with cervical disk herniation. Extended posture of the
      cervical spine during MRI may lead to acute neurological deterioration.

PMID- 20806757
TI  - Multi-level total en bloc spondylectomy for solitary lumbar metastasis of myxoid
      liposarcoma.
AB  - This article reports a case of solitary lumbar metastasis of myxoid liposarcoma
      treated by multi-level total en bloc spondylectomy. Myxoid liposarcoma has a
      predisposition to initial metastasis at an extrapulmonary site including bone.
      However a bone scan and FDG-PET, which are generally used for a whole-body
      screening of metastasis, are not sensitive to bone metastasis from myxoid
      liposarcoma. These situations make it difficult to achieve curative resection of
      a bone metastasis, especially in the spine. The patient was a 54-year-old man who
      had an intralesional excision of soft tissue tumor in the right thigh. He had an
      additional expansive excision due to the histological diagnosis of myxoid
      liposarcoma at the initial surgery. Four years postoperatively, L3 metastasis
      expanding to the adjacent vertebrae was detected using magnetic resonance
      imaging. Plain radiographs and computed tomography showed no evidence of the
      tumor involving the lumbar spine. A bone scan was false-negative although FDG-PET
      showed mild uptake. There was no other metastasis on the further examination.
      Multi-level total en bloc spondylectomy was performed using a combined posterior
      anterior approach. The lumbar nerves were dissected and preserved. The vertebral
      bodies of L2, 3 and the upper half of L4, which had been invaded by the tumor,
      were removed en bloc using an anterolateral extraperitoneal approach. He had no
      local recurrence or further metastasis until he died of ischemic cardiac disease
      14 months postoperatively.

PMID- 20806758
TI  - Sequential compression device may cause peroneal nerve palsy.
AB  - This article presents 2 cases of foot drop after joint replacement surgery that
      presented after sequential compression device application. In both cases, intact
      peroneal nerve function was documented by the surgeon in the recovery room prior
      to sequential compression device application. We believe that excessive pressure
      over the superficial aspect of the peroneal nerve in conjunction with decreased
      pain stimulus from analgesia may have contributed to these complications. We
      maintain sequential compression devices are the current mechanical
      thromboprophylaxis of choice; however, 4 recommendations are made to minimize the
      chances of this potential complication. First, precise attention should be given
      to patients who are short statured, as these patients can be more susceptible to
      having a sequential compression device improperly placed over the peroneal nerve
      at the fibular neck. Second, we recommend different size options become more
      widely available to accommodate varying patient sizes such that placement of the
      device is ensured to be distal to the fibular neck. Third, when using sequential
      compression device brands that have hook and look fastener straps, the straps
      should not be tight on application and frequent skin checks should be made to
      look for signs of over-compression. Lastly, we recommend considering delaying
      postoperative application of the sequential compression device until resolution
      of sensation following spinal or epidural anesthetic.

PMID- 20806759
TI  - Arthroscopic treatment of pigmented villonodular synovitis involving bilateral
      shoulders.
AB  - Pigmented villonodular synovitis (PVNS) is a lesion of benign proliferative
      synovium that invades joint, tendon sheath, and bursa. It mainly occurs in 1
      joint, the knee joint or hand, and multi-joint invasion is reported to be <1%.
      Rare cases have been reported of PVNS occurring in the shoulder joint. Generally,
      total synovectomy is a standard treatment of PVNS. However, complete synovectomy
      is sometimes impossible because of difficulty of visualization and access to the
      whole joint and subacromial space. Therefore, recurrence of the disease is always
      of concern. This article presents a case of 64-year-old patient with pain and
      swelling of bilateral shoulder joints of 4 months' duration. Physical examination
      showed atrophy of the deltoid and infraspinatus and a mass-like protrusion on the
      anterior portion of left shoulder. Active forward elevation was limited to 30
      degrees on the right and 90 degrees on the left. Overall synovial hyperplasia and
      nodular mass was observed on magnetic resonance imaging. Massive rotator cuff
      tear and invasion of the lesion toward the subacromial space and deltoid muscle
      was noted as well. Arthroscopic examination revealed a typical finding of PVNS:
      yellowish brown pigmentation over the overall joint capsule and subacromial
      space. Arthroscopic total synovectomy without rotator cuff repair was performed
      for both shoulders. Clinical outcomes showed good pain relief and no recurrence
      of the disease, although range of motion and muscle strength was not
      significantly improved, possibly due to accompanied massive rotator cuff tear.
      Arthroscopic total synovectomy in the treatment of PVNS of the shoulder joint is
      a minimally invasive and effective method, which makes it possible to access the
      whole joint space and subacromial space.

PMID- 20806760
TI  - Subdeltoid lipoma: a case with symptoms mimicking glenohumeral instability and
      subacromial impingement.
AB  - Lipoma is the most frequently occurring benign soft tissue tumor in the shoulder
      and the axillary region in middle-aged and older persons, yet few such lipoma
      cases have been associated with clinical symptoms. A 38-year-old right-handed man
      presented with an enlarged feeling and a painful back-and-forth popping in his
      left shoulder. Although moderate tenderness of the subacromial bursa and
      bicipital groove existed, an obvious impingement sign was absent. Also not
      evidenced were signs of neurological deficits, limited range of motion, or any
      physical findings suggestive of instability. Magnetic resonance imaging showed a
      homogenous tumor in the subdeltoid that was isointense relative to the
      subcutaneous fat and fluid collection in the hypertrophic subacromial bursa. As
      the tumor was considered from the clinical and imaging findings to be
      attributable to all clinical symptoms, it was resected en bloc with a
      satisfactory result. Histopathologically, the tumor showed typical features of a
      simple lipoma. To our knowledge, the present case is the first of a subdeltoid
      intermuscular lipoma of which mechanism developing symptoms was preoperatively
      surmised from imaging. The symptom-mimicking shoulder instability was assumed to
      be produced by the back-and-forth snapping of the lipoma beneath the deltoid
      muscle. The mechanism for developing the subacromial impingement-like symptom was
      surmised to derive from the middle deltoid fibers pressuring the lipoma to push
      up into the subacromial space. This case is presented to emphasize the careful
      reading of imaging in considering the pathomechanism of the attributing symptoms.

PMID- 20806761
TI  - Unusual combination of posterior femoral head dislocation with anterior and
      posterior wall fractures in the ipsilateral acetabulum.
AB  - Although hip dislocation combined with acetabular fracture is not an uncommon
      injury, anterior acetabular wall fractures rarely occur in patients who have
      posterior fracture-dislocations of the hip. This article presents a unique case
      of anterior and posterior wall fractures of the ipsilateral acetabulum in a
      patient who sustained traumatic posterior hip dislocation that resulted from a
      high-speed motor vehicle accident. The initial imaging evaluation, which did not
      include the obturator oblique view, revealed no concomitant anterior acetabular
      wall fracture. Repeated manipulative reductions were unsuccessful in reducing the
      displaced hip joint. Pelvic computed tomography (CT) scans revealed the initially
      missed anterior acetabular wall fracture fragments incarcerated in the left hip
      joint in addition to the hip dislocation and the posterior acetabular wall
      fracture. The incarcerated bone fragments lay between the anterior wall and the
      femoral head, and between the posterior wall and the femoral head, which appeared
      to derive from both anterior and posterior acetabular walls, respectively. Open
      reduction and internal fixation was performed to manage the posterior dislocation
      and associated acetabular fractures. Intraoperatively, the major anterior wall
      fragment was used to reconstruct the defected posterior wall. This case
      highlights the necessity of suspicion and pre- and postoperative monitoring of
      the obturator oblique view and CT scans to detect the potentially existing
      anterior acetabular wall fracture. Early surgical intervention is important to
      guarantee satisfactory outcomes of such complex fracture-dislocation injuries.

PMID- 20806762
TI  - Pyoderma gangrenosum complicating bilateral total knee arthroplasty.
AB  - Pyoderma gangrenosum is an ulcerative, necrotic dermatosis of unknown etiology.
      It is frequently associated with inflammatory, hematologic, or neoplastic
      disease. Clinical and physical evaluation can imitate postoperative wound
      infections. This article reports a case of pyoderma gangrenosum in a patient who
      underwent bilateral total knee arthroplasty. Her postoperative course was
      complicated by wound dehiscence and ulceration in both knees. Her condition
      deteriorated despite debridements and antibiotic therapy. Deep intraoperative
      cultures were all negative. Once the diagnosis of pyoderma gangrenosum was
      established and once appropriate treatment with steroids was initiated, her
      condition improved. The diagnosis of pyoderma gangrenosum should be considered in
      patients with wound deterioration who remain culture-negative and fail to respond
      to debridement and antibiotic treatment. This case report highlights the
      presentation of pyoderma gangrenosum and its ability to be misdiagnosed as
      infection. A delay in treatment may result in unnecessary surgery that will
      further exacerbate this inflammatory condition.

PMID- 20806763
TI  - Acute tibial compartment syndrome following spine surgery.
AB  - This article presents a case of a patient with popliteal artery occlusion
      following anterior and posterior instrumented fusion of the lumbar spine. No
      previous study has reported acute anterior tibial compartment syndrome due to
      popliteal artery occlusion and restricted venous return following spine surgery.
      A 53-year old female, with a twice failed fusion of L5-S1, underwent L3-S1
      anterior interbody and posterior L3-S1 instrumented fusion. Due to postoperative
      continuous analgesia, the patient was sleepy and confused on postoperative day 1.
      On the postoperative day 2, the right calf and anterolateral tibia manifested
      clinical signs of compartment syndrome and both thighs exhibited pressure
      ecchymoses from the antiembolism stockings. Fasciotomies of the right tibial
      compartments were undertaken and necrosis of the anterior compartment muscles was
      found. Intraoperative arteriogram revealed occlusion of the right popliteal
      artery and thrombectomy was performed. Lupus anticoagulant was found to be
      responsible for patient's coagulopathy. During postoperative year 1, the patient
      still had weakness and recurrent edema of the right foot. Unrecognized limb
      ischemia and possibly restricted venous return were the causes of the compartment
      syndrome. Surgeons should be aware of this devastating complication of spine
      surgery.

PMID- 20806764
TI  - Progression of aggressive metastatic carcinosarcoma after treatment of
      epithelioid osteosarcoma.
AB  - Osteosarcoma is the most common primary malignant osseous neoplasm, constituting
      approximately 35% of skeletal malignancies. The different subtypes of
      osteosarcoma are differentiated based on clinical, histologic, and radiographic
      data, as well as the variable amount of osteoid produced by malignant cells. The
      epithelioid osteosarcoma subtype accounts for only 5.7% of all osteosarcomas and
      portends an extremely poor prognosis. The 5-year survival rate for patients with
      epithelioid osteosarcoma treated with surgery (with or without chemotherapy) is
      13.5%. This is in direct contrast to the >70% ten-year survival rate of
      conventional osteosarcoma treated with surgery and chemotherapy. This article
      presents a fatal case of epithelioid osteosarcoma in an 11-year-old girl with
      right knee pain of 6 months' duration. Biopsy demonstrated morphologic findings
      consistent with high-grade osteosarcoma with epithelioid features. The
      epithelioid component was positive for vimentin and CD99; however, fluorescent in
      situ hybridization for the (11;22) translocation was negative. In this case, the
      epithelioid cells failed to respond to conventional or subsequent experimental
      chemotherapy for osteosarcoma and eventual metastasized to the lymph nodes and
      lungs despite multiple ablative surgeries. This case report supports the concept
      of carcinosarcoma with malignant cells lines arising from 2 different cellular
      lineages or a common cellular precursor. The epithelial component was more
      aggressive than the cells of mesenchymal origin, highlighting the need for
      continued research and a more favorable outcome for this rare subset of
      osteosarcoma.

PMID- 20806765
TI  - Dynamic compression plate and cancellous bone graft for aseptic nonunion after
      intramedullary nailing of femoral fracture.
AB  - We evaluated the effect of revision with dynamic compression plate and cancellous
      bone graft for aseptic nonunion after intramedullary nailing of femoral shaft
      fracture. Fifty patients with aseptic nonunion of femoral shaft fracture after
      intramedullary nailing were reviewed and analyzed retrospectively between 1996
      and 2007. There were 40 men and 10 women with an average age of 44 years (range,
      19-76 years). Thirty-five were diaphyseal fractures, 8 were distal fractures, and
      7 were proximal fractures. Twenty-eight fractures were defined as atrophic
      nonunion, 13 fractures were hypertrophic nonunion, and 9 fractures could not be
      defined clearly. All fractures were managed by retaining previous implants, open
      reduction and internal fixation with dynamic compression plate, and
      supplementation by cancellous bone graft. The average follow-up period was 76
      months (range, 24-128 months). Functional evaluations were done by Harris Hip
      score and Hospital for Special Surgery knee score. All nonunions united on
      average at 24 weeks (range, 18-32 weeks). One superficial wound infection
      occurred. At follow-up, each patient was evaluated to have satisfactory function
      results, with near normal hip/knee functions without noticeable pain, and full
      return to preinjury activities/work without pain.Augmentative dynamic compression
      plate with cancellous bone graft is a reliable and effective treatment for
      revision of aseptic nonunion of femoral shaft fracture after intramedullary
      nailing.

PMID- 20806766
TI  - Evaluation of a noninvasive expandable prosthesis in musculoskeletal oncology
      patients for the upper and lower limb.
AB  - The noninvasive expandable prosthesis is used for limb-salvage surgery following
      tumor resection in skeletally immature patients. The purpose of this
      retrospective study is to report our experience with the Repiphysis (Wright
      Medical Technology, Inc; Arlington, Tennessee) noninvasive expandable prosthesis
      for both the lower extremity and compassionate use in the upper extremity in 12
      patients between 2003 and 2008. Twelve prostheses were implanted in 12 patients
      with an average follow-up of 38 months (range, 12-78 months). Nine patients
      underwent a total of 38 expansion procedures. Mean total expansion was 4.5 cm
      (range, 0.8-9.9 cm). No complications of lengthening occurred. Seven nononcologic
      complications were noted. One infection was reported in 12 patients. The mean
      MSTS score after rehabilitation was 24.5 (range, 13-30). The Repiphysis
      noninvasive prosthesis provides acceptable functional outcomes for both upper and
      lower extremity implantation and appears to have an advantage as compared to
      conventional expandable prosthetics, which require open procedures that can
      potentially increase the risk of infection from repeated hardware exposure.

PMID- 20806767
TI  - Bone tumors of the clavicle: risk of malignancy in the elderly and safe needle
      biopsy.
AB  - The clavicle is a rare site for bone tumors and little is known from the limited
      literature about the prognostic factors and management techniques, including
      biopsy. The method of biopsy is controversial in the clavicle because of the risk
      of injury to the neighboring neurovascular structures. Twenty patients with
      clavicular lesions were retrospectively reviewed with clinical, radiological, and
      histopathological reports. A needle biopsy was planned in the presence of an
      osteolytic lesion providing nonforceful entry of the needle, detailed knowledge
      obtained about the local anatomy, and known availability of an oblique angle for
      the needle entry away from vascular structures. A needle or tru-cut biopsy was
      performed for preoperative histopathological diagnosis in 6 selected patients
      with no complications. Considering the histological diagnosis and prevalence of
      clavicular bone tumors, benign and malignant lesions had a similar prevalence
      rate; however, malignant tumors occurred in an older (>50 years) population
      (P=005). Statistical analysis revealed that the best cutoff point for age for
      discriminating malignant lesions was 50 years with high sensitivity. The main
      concern for these patients is primary lesion site treatment and symptom
      palliation. Every clavicular lesion in patients older than 50 years should be
      considered as malignant unless proven otherwise. This article demonstrates that
      needle biopsy can be performed safely in selected lesions with particular
      attention to cross-sectional local anatomy during needle insertion.

PMID- 20806768
TI  - Pulmonary gas exchange impairment following tourniquet deflation: a prospective,
      single-blind clinical trial.
AB  - The tourniquet has been considered as a recognized cause of limb
      ischemia/reperfusion injury in orthopedic surgery resulting in a transient
      neutrophil, monocyte activation, and enhanced neutrophil transendothelial
      migration with potential remote tissue injury. This study investigated the effect
      of unilateral tourniquet application within a safe time limit on pulmonary
      function and the roles of lipid peroxidation and systemic inflammatory response.
      Thirty patients undergoing unilateral lower extremity surgery with or without
      tourniquet were equally divided into a control group with no tourniquet (Group C)
      and a tourniquet (Group T). Arterial partial pressure of oxygen (P(a)O(2)),
      arterial-alveolar oxygen tension ratio (a/A ratio), alveolar-arterial oxygen
      difference (A-aDO(2)) and respiratory index, plasma malondialdehyde, serum
      interleukin (IL) -6 and IL-8 levels were measured immediately before and 1 hour
      after tourniquet inflation/operation beginning, 0.5, 2, 6, and 24 hours after
      tourniquet deflation/operation ending. The results represented no significant
      changes in Group C with regard to either blood gas variables or levels of
      circulating mediators, while blood gas variable changes of greater A-aDO(2) and
      respiratory index and lower PaO2 and a/A ratio were shown at 6 hours following
      tourniquet deflation. The levels of malondialdehyde, IL-6, and IL-8 were
      increased over baseline values from 2 to 24 hours following tourniquet deflation
      in Group T. We concluded that tourniquet application within a safe time limit may
      cause pulmonary gas exchange impairment several hours after tourniquet deflation,
      where lipid peroxidation and systemic inflammatory response may be involved.

PMID- 20806769
TI  - Osteomyoplastic and traditional transtibial amputations in the trauma patient:
      perioperative comparisons and outcomes.
AB  - We hypothesized that patients undergoing transtibial amputation osteomyoplasty
      would have better functional outcomes than patients undergoing traditional
      transtibial amputation. We conducted a retrospective review of the medical and
      radiographic records to evaluate and compare 26 patients who underwent
      transtibial amputation osteomyoplasty and 10 patients who underwent traditional
      transtibial amputation, with specific attention to perioperative complications
      and functional outcomes. At >1 year follow-up, patients who underwent amputation
      osteomyoplasty had significantly improved rates of return to work and decreased
      rates of revision than patients who underwent traditional transtibial amputation.
      Sickness Impact Profile questionnaire results completed at a mean of 28 months
      postoperatively showed significantly better overall scores and physical and
      psychosocial dimension scores for amputation osteomyoplasty patients. Based on
      the results of this study, the outcomes of amputation osteomyoplasty appear to be
      safe and may be more beneficial than traditional amputation, in terms of improved
      functional outcomes for patients after severe lower-extremity trauma.

PMID- 20806770
TI  - Weight and body mass index change after total joint arthroplasty.
AB  - Obesity has become a leading public health issue in the United States. The goal
      of this study was to examine whether patients experience a significant change in
      body mass index (BMI) or weight after total joint arthroplasty. Previous studies
      have not corrected for the natural, annual positive BMI change in North Americans
      aged 29 to 73 years. Our study takes this natural weight gain into consideration
      in examination of total hip arthroplasty (THA) and total knee arthroplasty (TKA)
      populations. Our study population trended toward weight loss and BMI loss when
      weight was corrected for natural gain. Clinically significant weight loss, as
      determined by US Food and Drug Administration parameters, occurred in 19.9% of
      the study population when weight was corrected for natural gain. The TKA
      population exhibited a statistically significant (P<.05) weight loss and a
      clinically significant weight loss in 21.5% of the population. Patients with an
      initial BMI >30 exhibited a trend toward weight loss. This study was a level II
      retrospective study.

PMID- 20806771
TI  - Clinical results of reversed V-shaped high tibial corticotomy with minimally
      invasive surgery without internal fixation devices.
AB  - High tibial osteotomy is a method of treating knee osteoarthritis due to genu
      varum in advanced stages. High tibial osteotomy-associated problems continue to
      be reported. The purpose of this study was to investigate the clinical results of
      a new, innovative method of high tibial osteotomy with 3- to 13-year follow-up.
      Between 1996 and 2006, our new surgical method was performed on 293 patients with
      medial compartment osteoarthritis and genu varum. All patients were examined
      preoperatively, 6 months postoperatively, and at final follow-up. The Hospital
      for Special Surgery Knee Scoring System (HSS) was used at final follow-up, and
      limb alignment and patient satisfaction were reassessed. Immediate postoperative
      complications included varus recurrence, knee instability, and peroneal nerve
      palsy, and no signs of tibial nonunion or infection were observed. At final
      follow-up, 3 cases of genu recurvatum, 2 cases of peroneal nerve palsy, and 25
      cases of loss of correction were observed. Average postoperative HSS score was 85
      (range, 47-97), and 97.8% of the patients were satisfied. This new method is a
      good alternative for the correction of genu varum because it requires a small
      incision, is soft tissue friendly, is a corticotomy instead of an osteotomy,
      requires no internal or external fixation devices, has a shorter duration and an
      acceptable complication and recurrence rate, and results in satisfactory HSS
      scores and higher patient satisfaction rates.

PMID- 20806772
TI  - Comparison of early fixation and delayed reconstruction after displacement in
      previously nondisplaced acromion fractures.
AB  - Scapular fractures account for approximately 1% of all fractures, and 8% to 10%
      are acromion fractures. We compared the results of early and delayed treatment
      for nondisplaced and type III acromion fractures, respectively, to investigate an
      early treatment method for nondisplaced acromion fractures. Patients treated
      between March 1999 and March 2006 with 2-year follow-up were selected for the
      study. The early fixation group comprised 16 patients, and the delayed
      reconstruction group comprised 18 patients. Moreover, the delayed reconstruction
      group was further divided into 2 additional groups: delayed group B and delayed
      group N. Delayed group B comprised 7 cases receiving bone graft, and delayed
      group N comprised 11 cases not receiving bone graft. Mean Constant scores were
      significantly greater for the early fixation group (92+/-6.6; range, 64-98) than
      for both delayed groups N (86+/-7.8; range, 54-96) and B (81+/-9.4; range, 58-92)
      (P=.042 and .024, respectively). Mean pain score was 14+/-4.8 (range, 5-15) in
      the early fixation group, 12+/-7.4 (range, 5-15) in delayed group N, and 9+/-8.8
      (range, 5-15) in delayed group B (P=.052 and .018, respectively). Mean daily
      activity score was also significantly greater in the early fixation group (19+/
      6.4; range, 16-20) than in both delayed group N (14+/-6.2; range, 10-18) and
      delayed group B (10+/-4.4; range, 8-18) (P=.048 and .021, respectively). The P
      values for Constant, pain, and daily activity scores between delayed groups N and
      B were .048, .038, and .052, respectively. In cases of young patients with type
      IC acromion fractures at the time of injury, a high activity level, and the early
      need for crutches or a walker, early surgical treatment should be considered.

PMID- 20806773
TI  - Outcomes and practical information for patients choosing nonoperative treatment
      for distal biceps ruptures.
AB  - The goal of this study was to evaluate the outcomes of patients selecting
      nonoperative treatment for distal biceps tendon ruptures to provide information
      to patients and caregivers to consider in decision making. Five men
      conservatively treated for distal biceps tendon rupture between November 2002 and
      December 2006 were compared to 5 age-matched controls treated operatively.
      Outcomes at 4.5 years included supination strength, range of motion, and American
      Shoulder and Elbow Surgeons (ASES) score. Two groups of 9 normal volunteers--1
      young group averaging 30.7 years and 1 older group averaging 48.8 years--served
      as controls. In nonoperative patients, elbow supination strength in the injured
      arm was 4.14 Nm (SD 0.94) and in the uninjured arm was 4.91 Nm (SD 0.65). In
      operative patients, supination strength was 4.25+/-1.08 Nm in the operatively
      repaired arm and 5.74+/-1.27 Nm in the uninjured arm. Age-matched normal patients
      had supination strength of 5.78+/-1.46 Nm in the dominant arm and 5.59+/-1.32 Nm
      in the nondominant arm. The ASES score averaged 89.57, with 3 patients reporting
      pain, compared to a score of 87.5 in the operative patients. Patients choosing
      conservative treatment for distal biceps ruptures have residual pain and weakness
      approximately double that seen between normal dominant and non-dominant
      extremities.

PMID- 20806774
TI  - Efficacy of outpatient bilateral simultaneous hallux valgus surgery.
AB  - Bilateral simultaneous hallux valgus correction is traditionally performed as an
      inpatient procedure due to concerns regarding adequate postoperative analgesia
      and difficulty mobilizing. We prospectively evaluated 40 consecutive patients (80
      feet) who underwent outpatient surgical correction of bilateral symptomatic
      hallux valgus. Patients underwent preoperative radiological and clinical
      assessment using pain and American Orthopaedic Foot & Ankle Society (AOFAS)
      hallux assessment scores. Patients underwent preoperative counseling and were
      assessed for medical suitability for outpatient surgery. They were instructed to
      have responsible adult caregivers available for 24 hours postoperatively, easy
      access to after-hours emergency medical care, and access to a telephone.
      Procedures were performed under general anesthesia with local anesthetic ankle
      block. Postoperatively, patients were discharged after assessment by medical,
      nursing, and physiotherapy staff with an oral analgesia regimen. Cast
      immobilization was not used. Patients were reviewed at 6 weeks and 3 months
      postoperatively with repeated clinical and radiological assessment. All patients
      were discharged home and none required inpatient ward admission. Post-discharge,
      no patient presented to the emergency department or their general practitioner as
      a consequence of poor pain control. At final follow-up assessment, mean AOFAS
      hallux scores had improved from 58.1 (range, 29-80) to 89.0 (range, 47-100)
      (P<.001). The mean hallux valgus angle improved from 33.2 degrees (range, 15
      degrees -53 degrees) to 16.9 degrees (range, 3 degrees -39 degrees) and the
      intermetatarsal angle had improved from 13.2 degrees (range, 6 degrees -23
      degrees) to 8.5 degrees (range, 4 degrees -15 degrees) (P<.001). Eighty-five
      percent of patients reported that they would recommend outpatient surgery.
      Bilateral hallux valgus surgery can be performed safely as an outpatient
      procedure in selected patients with acceptable levels of patient satisfaction.

PMID- 20806775
TI  - Hip hemiarthroplasty after displaced femoral neck fracture: a survivorship
      analysis.
AB  - The standard of care for displaced femoral neck fractures is not clear. We
      reviewed all patients 65 years or older with displaced femoral neck fracture who
      underwent hip hemiarthroplasty at our institution between 1997 and 2006. Women
      accounted for 70% of the patients. Mean patient age was 78 years, and most of the
      patients were community ambulators. Complete operative information was available
      for 226 (79%) of 285 patients. Follow-up was available for 126 patients (mean,
      15.8 months; range, 1-97 months). Total mortality rate was 58%. Mean University
      of California, Los Angeles (UCLA) scores were 8.3 for pain, 6.7 for walking, 5.6
      for function, and 3.5 for activity. Two patients had acetabular wear on
      radiography, but symptoms were not severe enough to warrant revision. Three
      patients (1.3%) underwent revision, 1 with acetabular wear and 2 for infection.
      Despite the limited follow-up, the rate of conversion to total hip arthroplasty
      (THA) was low. Longer, prospective studies are needed to delineate which patients
      will benefit from THA.

PMID- 20806776
TI  - Biomechanical comparison of extensile exposures in total knee arthroplasty.
AB  - The "banana peel" exposure is a novel technique for knee joint exposure that
      consists of partially peeling the patellar tendon off the tibia, leaving the
      extensor mechanism intact distally and laterally. Although good clinical results
      have been reported with this technique with no disruption of the extensor
      mechanism, concerns exist that it could cause extensor lag, quadriceps weakness,
      or patellar tendon rupture. We compared the banana peel exposure repair to tibial
      tubercle osteotomy repair, which we chose as our benchmark procedure because much
      is known about its associated healing and rehabilitation protocols. In our study
      of 16 paired, fresh-frozen human knee specimens, the 2 techniques were used
      alternately for the right and left knees. To measure acute strength, 10 pairs
      were tested. The patella was clamped and pulled superiorly at 25 mm/min until
      failure. For cyclical testing (6 pairs), the knee was extended from 90 degrees of
      flexion to 0 degrees for 2000 cycles at 0.25 Hz while we monitored the distance
      between the inferior pole of the patella and the tibial diaphysis using a passive
      optical kinematic measuring system. Mean failure strengths of the banana peel and
      osteotomy groups were 2642+/-1104 N and 2123+/-562 N, respectively, suggesting
      that the banana peel repair is not weaker than the osteotomy repair. Neither
      group had a significant increase (via paired Student t test, P>.05) in the
      distance between the inferior pole of the patella and the tibial diaphysis,
      suggesting that neither exposure would result in extensor lag.

PMID- 20806777
TI  - The influence of atorvastatin on tendon healing: an experimental study on
      rabbits.
AB  - Hyperlipidemia is a major risk factor for coronary heart disease. The most
      commonly used antihyperlipidemic drugs are 3-hydroxy-3-methylglutaryl coenzyme A
      (HMG CoA) reductase inhibitors (statins), of which atorvastatin is one of the
      most widely used. Little is known about the relationship between tendinopathy and
      HMG CoA reductase inhibitors (statins) or the effects of atorvastatin use on
      tendon healing following surgical repair of tendon rupture. We hypothesized that
      atorvastatin negatively affects this healing process. The Achilles tendons of 16
      New Zealand rabbits were ruptured surgically and repaired with sutures. Eight of
      the rabbits were given oral atorvastatin. The other 8 served as a surgical
      control group. Six weeks postoperatively, all the rabbits were sacrificed, and
      the repaired tendons were removed. After standard histological preparation,
      fibroblastic activity, re-vascularization, collagenization, collagen
      construction, and inflammatory-cell infiltration were evaluated. On comparing the
      atorvastatin and surgical control groups, we observed no difference in
      fibroblastic activity. Although it did not reach statistical significance in our
      study, a difference was noted in revascularization, collagenization, and
      inflammatory cell infiltration; and a statistical difference was observed in
      collagen construction. Doubt remains about the adverse effect of atorvastatin use
      during tendon healing. Further investigations in animal and human models are
      needed on the effects of tendon healing when atorvastatin is administered for a
      longer time frame prior to the injury.

PMID- 20806778
TI  - Young and burgess type I lateral compression pelvis fractures: a comparison of
      anterior and posterior pelvic ring injuries.
AB  - The goals of this study were to find associations between anterior and posterior
      ring injuries, provide a descriptive comparison of pelvic ring disruptions as
      assessed by plain radiography, and compare the value of computed tomography (CT)
      over plain radiography in evaluating anterior and posterior structures. A
      retrospective review of radiographic reports and records identified 142 patients
      with pubic ramus fractures as observed by plain radiography. A statistical
      analysis was performed to test the associations between anterior ring injury as
      assessed by plain radiography and posterior ring injury as assessed by CT. Forty
      five point five percent of patients with bilateral ramus fractures and 42.0% of
      patients with dual-ramus fractures had concomitant sacral fractures not observed
      on plain radiographs. These occult sacral fractures were found in only 11.1% of
      patients with inferior ramus fractures. The type of pubic injury on plain
      radiographs may be predictive of posterior ring injury, and therefore may help
      determine injury energy and severity, determine the need for further imaging
      studies, and help guide clinical management. Although CT is highly sensitive in
      identifying both anterior and posterior pubic ring injuries, elderly patients
      with simple fractures of a single pubic ramus are less likely to suffer from
      pelvic instability and thus may not benefit from CT.

PMID- 20806779
TI  - The protein-free IANUS peptide array uncovers interaction sites between
      Escherichia coli parvulin 10 and alkyl hydroperoxide reductase.
AB  - The reliable identification of interacting structural elements without prior
      isolation of interacting proteins can be achieved by using the novel fluorescence
      resonance energy transfer-coupled IANUS (Induced orgANization of strUcture by
      matrix-assisted togethernesS) peptide array. Here we report that parvulin 10
      (Par10), an abundant Escherichia coli peptidyl prolyl cis/trans isomerase
      (PPIase), physically interacts with the alkyl hydroperoxide reductase subunit C
      (AhpC) in bacterial cell extracts, as determined by affinity chromatography and
      chemical cross-linking experiments. A Par10-negative E. coli strain showed
      increased sensitivity toward hydrogen peroxide compared to the wild-type strain.
      The IANUS experiment revealed three segments of the peroxiredoxin AhpC chain as
      potential Par10 binding partners. Inhibition of the Par10 PPIase activity by the
      corresponding AhpC-derived peptides as well as NMR data of (15)N-labeled Par10 in
      the presence of the AhpC(115-132) peptide or full-length AhpC confirmed that the
      putative Par10 active site is involved in the Par10-AhpC interaction. Moreover,
      NMR-based docking calculations as well as NOESY exchange peaks between the
      proline cis and trans isomers revealed the Asp125-Pro126 moiety of the AhpC
      segment G115-A132 as a substrate for Par10 enzymatic action. On the basis of
      these data, we conclude that Par10 catalytic activity is involved in the cellular
      protection against oxidative stress.

PMID- 20806780
TI  - Optical properties of light-emitting nematic liquid crystals: a joint
      experimental and theoretical study.
AB  - Semiempirical quantum-chemical calculations are used to simulate the optical
      properties of a series of green light-emitting nematic liquid crystals containing
      fluorene, thiophene, or thienothiophene groups with solid-state photoluminescence
      quantum efficiencies up to 0.36. We use a simple model of two parallel and
      closely spaced molecules in an anticofacial configuration to study intermolecular
      interactions in the solid state and slide one past the other to mimic the high
      orientational and low positional order of the nematic phase. We find that
      switching between H and J aggregates can be triggered by longitudinal
      displacements of the molecules with respect to one another by an extent that
      closely follows the chemical structure of the interacting chromophores. We
      discuss the implications of aggregate formation for efficient light emission in
      conjugated oligomers and polymers that show nematic or smectic order.

PMID- 20806781
TI  - Rapid collapse into a molten globule is followed by simple two-state kinetics in
      the folding of lysozyme from bacteriophage lambda.
AB  - Stopped-flow fluorescence and circular dichroism spectroscopy have been used in
      combination with quenched-flow hydrogen exchange labeling, monitored by two
      dimensional NMR and electrospray ionization mass spectrometry, to investigate the
      folding kinetics of lysozyme from bacteriophage lambda (lambda lysozyme) at pH
      5.6, 20  degrees C. The first step in the folding of lambda lysozyme occurs very
      rapidly (tau < 1 ms) after refolding is initiated and involves both hydrophobic
      collapse and formation of a high content of secondary structure but only weak
      protection from (1)H/(2)H exchange and no fixed tertiary structure organization.
      This early folding step is reflected in the dead-time events observed in the far
      UV CD and ANS fluorescence experiments. Following accumulation of this kinetic
      molten globule species, the secondary structural elements are stabilized and the
      majority (ca. 88%) of refolding molecules acquire native-like properties in a
      highly cooperative two-state process, with tau = 0.15 +/- 0.03 s. This is
      accompanied by the acquisition of substantial native-like protection from
      hydrogen exchange. A double-mixing experiment and the absence of a denaturant
      effect reveal that slow (tau = 5 +/- 1 s) folding of the remaining (ca. 12%)
      molecules is rate limited by the cis/trans isomerization of prolines that are
      trans in the folded enzyme. In addition, native state hydrogen exchange and
      classical denaturant unfolding experiments have been used to characterize the
      thermodynamic properties of the enzyme. In good agreement with previous
      crystallographic evidence, our results show that lambda lysozyme is a highly
      dynamic protein, with relatively low conformational stability (DeltaG degrees (N
      U) = 25 +/- 2 kJ.mol(-1)).

PMID- 20806782
TI  - Surface-step-terrace-induced anomalous transport properties in highly epitaxial
      La0.67Ca0.33MnO3 thin films.
AB  - La0.67Ca0.33MnO3 thin films were epitaxially grown on miscut MgO(001) substrates
      by pulsed laser ablation. Electrical transport properties were studied by using
      an ultra high vacuum, four-probe STM system at different temperatures. Anomalous
      resistivity behavior and metal-insulator transition temperatures were found, both
      of which are highly dependent upon the miscut angle (1, 3, and 5 degrees ). These
      phenomena are attributed to the difference in residual strain that results from
      the difference in terrace widths of the vicinal surfaces.

PMID- 20806783
TI  - Bioactivity-guided isolation of 1,2,3,4,6-Penta-O-galloyl-D-glucopyranose from
      Paeonia lactiflora roots as a PTP1B inhibitor.
AB  - The inhibition of protein tyrosine phosphatase 1B (PTP1B) is of substantial
      interest for the treatment of type-2 diabetes mellitus. Using an in vitro enzyme
      assay with human recombinant PTP1B 1,2,3,4,6-penta-O-galloyl-D-glucopyranose was
      isolated from the roots of Paeonia lactiflora as an inhibitor of PTP1B, with an
      IC(50) value of 4.8 MUM. Additionally, 1 was shown to act as an insulin
      sensitizer in human hepatoma cells (HCC-1.2) at a concentration of 10 MUM. Thus,
      a potential new mechanism of action is provided explaining the antidiabetic
      properties of P. lactiflora.

PMID- 20806784
TI  - Liposomal leakage induced by virus-derived peptides, viral proteins, and entire
      virions: rapid analysis by chip electrophoresis.
AB  - Permeabilization of model lipid membranes by virus-derived peptides, viral
      proteins, and entire virions of human rhinovirus was assessed by quantifying the
      release of a fluorescent dye from liposomes via a novel chip electrophoretic
      assay. Liposomal leakage readily occurred upon incubation with the pH-sensitive
      synthetic fusogenic peptide GALA and, less efficiently, with a 24mer peptide (P1
      N) derived from the N-terminus of the capsid protein VP1 of human rhinovirus 2
      (HRV2) at acidic pH. Negative stain transmission electron microscopy showed that
      liposomes incubated with the rhinovirus-derived peptide remained largely intact.
      At similar concentrations, the GALA peptide caused gross morphological changes of
      the liposomes. On a molar basis, the leakage-inducing efficiency of the P1
      peptide was by about 2 orders of magnitude inferior to that of recombinant VP1
      (from HRV89) and entire HRV2. This underscores the role in membrane
      destabilization of VP1 domains remote from the N-terminus and the arrangement of
      the peptide in the context of the icosahedral virion. Our method is rapid,
      requires tiny amounts of sample, and allows for the parallel determination of
      released and retained liposomal cargo.

PMID- 20806785
TI  - Win-win?  Early ART could benefit individual patients, reduce HIV rates.  San
      Francisco takes a stand on issue.

PMID- 20806787
TI  - Dramatic results for opt-out HIV testing in prison.  Proportion of HIV tests
      increased quickly.

PMID- 20806786
TI  - Sexual, social factors place women at greater HIV risk.  Expert discusses
      findings in this Q&A.

PMID- 20806788
TI  - HIV patients can be vaccinated against TB.  Results show a whole cell vaccine
      works.

PMID- 20806789
TI  - Pregnant women: One test. Two lives.  CDC women's health director urges clinical
      action.

PMID- 20806790
TI  - Tetracycline and T-cell activation. Clinical efficacy may take toxic levels.

PMID- 20806791
TI  - Teaming up to provide HIV drugs to patients.

PMID- 20806792
TI  - FDA notifications.  FDA approves efavirenz insert revisions.

PMID- 20806793
TI  - Treatment.  Many with HIV start care too late, researchers say.

PMID- 20806794
TI  - Guidance.  Guideline implementation would reduce transmission, costs.

PMID- 20806795
TI  - Awareness. New program aimed at reducing risky sexual behaviors.

PMID- 20806796
TI  - Prisons.  Penological interest in wristbands outweighs inmate's rights.

PMID- 20806797
TI  - Asylum.  Board failed to issue statement to support denial of asylum.

PMID- 20806798
TI  - Posttraumatic stress response to HIV diagnosis can impact medication adherence.

PMID- 20806799
TI  - Co-infection: HIV and the great mimic syphilis.

PMID- 20806800
TI  - An examination of drug-drug interactions with raltegravir.

PMID- 20806801
TI  - Shining a light on thoracic aortic disease. Problems with the body's main
      pipeline for blood often overlooked, misdiagnosed.

PMID- 20806803
TI  - Diastolic heart failure.  Trouble arises when the heart can't properly relax.

PMID- 20806802
TI  - Red meat: avoid the processed stuff.  Beef, pork and other red meats are okay for
      the heart, but not hot dogs, cold cuts, and other processed meat.

PMID- 20806804
TI  - Stents make later surgery riskier than usual.

PMID- 20806805
TI  - A sweet, nutty plan for better cholesterol, blood pressure.

PMID- 20806806
TI  - Ask the doctor.  I had a nuclear exercise test last fall, and it was perfectly
      normal.  Imagine my surprise this spring when I developed burning chest pain that
      turned out to be a heart attack on the bottom part of my heart.  Did the doctors
      mess up the reading of my exercise test?

PMID- 20806807
TI  - [Imaging diagnosis. Q & A. Aortitis syndrome (a chronic stage)].

PMID- 20806808
TI  - Kallmann Syndrome and hypogonadotropic hypogonadism. Preface.

PMID- 20806809
TI  - Pediatric neuroendocrinology. Preface.

PMID- 20806810
TI  - Current indications for growth hormone therapy. Preface.

PMID- 20806811
TI  - A case of profound weight loss secondary to use of phentermine.
AB  - BACKGROUND: Obesity has become particularly prevalent in both the United States
      and worldwide. Mississippi continues to lead the nation in prevalence of obesity
      estimates. The proportion of morbidly obese subjects is increasing at a
      disproportionately greater rate and the burden of obesity and its complications
      are more prevalent among ethnic minorities. We present the unique case of a
      Choctaw lady with morbid obesity who has shown a profound response to
      pharmacotherapy with phentermine. METHODS: The clinical case history of the
      patient; a 34-year-old Choctaw lady with morbid obesity, hypertension,
      hyperlipidemia, and type 2 diabetes is presented, followed by discussion of
      issues relevant to impacting the obesity epidemic in Mississippi. RESULTS: A 34
      year-old Choctaw lady with 1.5 year follow up was noted to have a peak initial
      body mass index (BMI) of 62.6 kg/m2 and weight of 176 kg. Since commencement of
      phentermine, initially at 15 mg daily and slowly up-titrated to 37.5 mg daily,
      she has lost over 23 kg (13% of baseline peak weight) with a current weight of
      153 kg and BMI of 54.4 kg/m2. Accompanying the weight reduction has been
      sustained normal blood pressure and improvement in glycemic control. CONCLUSIONS:
      Phentermine is a viable and important adjunct in the medical approach to weight
      management in obese subjects. Its potential utility should be considered even
      among subjects with morbid obesity. Given its cost it could be a cost effective
      adjunct in comprehensive weight loss programs for Mississippi that may positively
      impact the ongoing obesity epidemic. There remains a need for more studies of
      phentermine to better define its place in obesity management.

PMID- 20806812
TI  - Does a multidisciplinary diabetes group education visit improve patient outcomes?
AB  - PURPOSE: Diabetes is a significant and growing public health concern, and patient
      education is the primary approach for self-management. The objective of this
      study is to assess the impact of a single session diabetes group education
      intervention. METHODS: The design is a one-group pretest/posttest evaluation.
      Participants were adult outpatients with diabetes who attended a single session
      group education visit and volunteered to participate in the study. Survey
      questions include the Single Item Literacy Screener and diabetes knowledge
      questions. The survey was mailed and collected before the group visit. Diabetes
      knowledge was collected immediately after the group visit and again by telephone
      one to four months later. Hemoglobin A1c (HbA1c), lipids, and blood pressure were
      collected from the patient electronic medical record before and, where available,
      three months after the group visit. Data analysis includes descriptive statistics
      and Students t-testing to determine pre- and posttest differences of diabetes
      knowledge and physiological markers. RESULTS: Thirty-eight adult outpatients
      participated in the study. Nearly half responded that they never needed to have
      someone help with written medical materials. There was a significant increase
      from pretest to immediate posttest diabetes knowledge scores (N = 3; M = 5.58 to
      M = 7.53 out of 10), t(38) = -5.217, p = < 0.001 and a significant decrease in
      HbA1c from pretest to posttest group education (M = 9.16 to M = 8.52), t(27) =
      2.185, p = .038. CONCLUSIONS: A single session diabetes group education visit is
      effective in increasing patients' diabetes knowledge and decreasing HbA1c levels.

PMID- 20806813
TI  - Halitosis: hindrance or hint?

PMID- 20806814
TI  - We have no cabs in Vicksburg.

PMID- 20806815
TI  - Like the Spartans at Thermopylae: Mississippi's docs stress need to reform health
      reforrn at interim AMA meeting.

PMID- 20806816
TI  - Mississippi Health First collaborative.

PMID- 20806818
TI  - [Merkel cell skin carcinoma].
AB  - Merkel cell carcinoma is a rare tumour of the skin. It affects predominantly
      elderly Caucasian males on sun-exposed areas of the skin. Distinctively more
      frequent and at significantly lower age, its incidence is higher in
      immunocompromised patients. In these patients we often observe the highly
      aggressive course of Merkel cell carcinoma and a fatal outcome. The incidence of
      Merkel cell carcinoma has been rising in recent years and is more dramatic than
      the increased incidence of cutaneous melanoma. More than one-third of Merkel cell
      carcinoma patients will die from this cancer, making it twice as lethal as
      melanoma. The malignant transformation of Merkel cells is currently thought to be
      related to an infection with Merkel cell polyomavirus. In the early stage the
      discreet clinical picture may be contrary to extensive microscopic invasion and
      this seemingly benign appearance can delay diagnosis or increase the risk of
      insufficient tumour excision. The diagnosis is definitely confirmed by
      histological evaluation and immunohistochemical tests. A typical feature is the
      tendency of Merkel cell carcinoma to frequent local recurrence and early
      metastasizing into regional lymph nodes with subsequent tumour generalization.
      The mainstay of therapy is radical excision of the tumour and adjuvant
      radiotherapy targeted at the site of primary incidence and local draining lymph
      nodes. The efficacy of different chemotherapy protocols in Merkel cell carcinoma
      is limited and the median survival rate is measured in months. In the future,
      prophylaxis with vaccination against Merkel cell polyomavirus will hopefully be
      possible in high-risk patients, as well as therapeutic usage of antisense
      oligonucleotides or microRNAs, eventually complete Merkel cell carcinoma
      elimination by affecting the tumour suppressor gene Atonal homolog 1 expression.
      The staging of the tumour at time of diagnosis is the most important prognostic
      factor. In this respect, the importance of preventative skin inspection in high
      risk immunocompromised patients must be stressed and suitable therapy must be
      indicated in suspected lesions.

PMID- 20806817
TI  - [ABL1, SRC and other non-receptor protein tyrosine kinases as new targets for
      specific anticancer therapy].
AB  - Non-receptor protein tyrosine kinases are responsible for signal transduction
      during many physiologic cellular processes, including cell growth and
      proliferation, apoptosis, differentiation, regulation of actin cytoskeleton, cell
      shape, adhesion, motility and migration. Aberrant activity of protein tyrosine
      kinases (acquired as a result of chromosomal translocation or point mutation) has
      been implicated in the stimulation of cancer growth and progression, the
      induction of drug-resistance, tumour neovascularization, tissue invasion,
      extravasation and the formation of metastases. Small molecule tyrosine kinase
      inhibitors interfere with these pathophysiological circuits by blocking the
      signalling cascades triggered by the aberrantly activated protein tyrosine
      kinases (e.g. BCR-ABL1, FIP1L1-PDGFRA or ETV6-PDGFRB).Tyrosine kinase inhibitors
      (imatinib, nilotinib, dasatinib) now belong to established anti-cancer agents
      with clinical activity in patients with CML, Ph+ ALL, and myeloid neoplasms with
      overexpression of PDGFRA, PDGFRB and wild-type KIT. New generation tyrosine
      kinase inhibitors (e.g. dasatinib) with extended activity against SRC and EPH
      kinases belong to promising anti-cancer agents with documented preclinical
      activity in several solid tumours (e.g. prostate cancer).

PMID- 20806819
TI  - [Molecular predictors in head and neck tumours].
AB  - This review summarizes biological markers of head and neck cancer, which have
      emerged from recent developments in molecular changes during carcinogenesis.
      These markers could be evaluated in every step that is believed to be necessary
      for the development of a cancer: acquisition of autonomous proliferative
      signalling (EGFR), proliferative activity of tumour cells (DNA content, Ki-67,
      mitotic index), inhibition of growth inhibitory signals (Bcl-2), apoptosis (p53),
      immortalization (telomerase), angiogenesis (CD34, VEGF) and metastasis (MMP-9, E
      cadherin, I-CAM aj.). Most of these biological markers are at the preclinical
      research stage. Significant progress has been achieved in the application of
      targeted therapy in head and neck cancer.

PMID- 20806820
TI  - [EGFR tyrosine kinase inhibitors as a targeted therapy for bronchioloalveolar
      carcinoma of the lung: a case report of a clinically prompt and intensive
      response and literature review].
AB  - INTRODUCTION: Bronchioloalveolar carcinoma (BAC) is an adenocarcinoma belonging
      to non-small cell lung carcinomas (NSCLC) that, in addition to its morphology and
      endobronchial spread, presents with certain specific clinical characteristics:
      greater incidence in women, non-smokers and younger patients, presence of
      malignant bronchorrhea and lower susceptibility to conventional cytostatic
      therapies in comparison to other subtypes of NSCLC. On the other hand,
      nonmucinous type of BAC may show better therapeutic response to targeted therapy
      with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI)
      erlotinib or gefitinib, as it is 5 times more frequently a carrier of EGFR gene
      mutations compared to conventional lung adenocarcinomas. CASE DESCRIPTION: We
      present a case of a 41 years old man, non-smoker for the last 5 years, who was
      diagnosed with a pneumonic form of nonmucinous bronchioloalveolar carcinoma.
      Metastases to regional and distant lymph nodes and massive involvement of
      skeleton with infiltrations in the bone marrow were present at the diagnosis.
      During the first line palliative chemotherapy with combination regimen of
      carboplatin and paclitaxel, the disease progressed significantly and the
      patient's condition deteriorated (performance status (PS) 3, severe dyspnoea at
      rest, malignant bronchorrhea). Subsequently, administration of erlotinib was
      initiated based on a series of case studies describing good response of BAC to
      treatment with EGFR TKI. An evident improvement of the patient's condition was
      observed as early as 4 days of administration, together with regression of
      peripheral lymphadenopathy. Nearly complete disappearance of pulmonary
      infiltrates was observed after 30 days of therapy, with the patient becoming
      asymptomatic, PS 0. Molecular genetics confirmed the tumour phenotype to be
      highly responsive to EGFR TKI therapy. The tumour contained EGFR mutation in exon
      19 (in-frame L747-753insS deletion) and wild-type K-ras. Disease relapse in the
      liver occurred 6 months later confirming disease progression. Further treatment
      remained ineffective despite brief stabilisations of liver enzyme progression
      following repeated administration of pemetrexed and gefitinib. The patient died
      12 months after the diagnosis. CONCLUSIONS: Our case confirms the importance of
      targeted therapy when treating tumours of an appropriate phenotype. Such
      treatment may have prompt and intensive effect that may reverse the course of the
      disease even in patients with poor overall health status.

PMID- 20806821
TI  - Bile duct malignancies.
AB  - Bile duct malignancies include intrahepatic cholangiocarcinoma (ICC),
      extrahepatic cholangiocarcinoma (ECC), gall bladder carcinoma (GC) and carcinoma
      of Vater's ampulla (ampulloma). Bile duct neoplasms are rare tumours with overall
      poor prognosis. The overall incidence affects up to 12.5 per 100,000 persons in
      the Czech Republic. The mortality rate has risen recently to 9.5 per 100,000
      persons. The incidence and mortality have been remarkably stable over the past 3
      decades. The survival rate of patients with these tumours is poor, usually not
      exceeding 12 months. The diagnostic process is complex, uneasy and usually late.
      Most cases are diagnosed when unresectable, and palliative treatment is the main
      approach of medical care for these tumours. The treatment remains very
      challenging. New approaches have not brought much improvement in this field.
      Standards of palliative care are lacking and quality of life assessments are
      surprisingly not common. From the scarce data it seems, however, that multimodal
      individually tailored treatment can prolong patients'survival and improve the
      health-related quality of life. The care in specialized centres offers methods of
      surgery, interventional radiology, clinical oncology and high quality supportive
      care. These methods are discussed in the article in greater detail. Improvements
      in this field can be sought in new diagnostic methods and new procedures in
      surgery and interventional radiology. Understanding the tumour biology on the
      molecular level could shift the strategy to a more successful one, resulting in
      more cured patients. Further improvements in palliative care can be sought by
      defining new targets and new drug development. The lack of patients with bile
      duct neoplasms has been the limiting factor for any improvements. A new design of
      larger randomized international multicentric clinical trials with prompt data
      sharing could help to overcome this major problem. Defining standards of
      palliative care is a necessity. Addressing health-related quality of life could
      help to assess the real benefit of palliative treatment.

PMID- 20806822
TI  - [Bortezomib in multiple myeloma patients after allogeneic stem cell
      transplantation].
AB  - Bortezomib represents a novel biological and targeted treatment modality with
      excellent treatment results in multiple myeloma patients. Bortezomib has also
      been successfully used several times in heavily pre-treated patients with myeloma
      relapse or progression after allogeneic stem cell transplantation. Its
      immunomodulatory effect, mediated, for instance, through the selective apoptosis
      of alloreactive T-lymphocytes and inhibition of the nuclear factor kappa B,
      brings the potential of graft versus host disease management, while the
      immunological anti-tumour effect remains preserved. Apart from thrombocytopenia,
      neurotoxicity most likely potentiated by concomitant and long-term use of
      cyclosporine is the major side effect of the treatment. The impact and modulation
      of graft versus host disease remains controversial in clinical practice.
      Bortezomib is effective and feasible in the post-transplant setting.

PMID- 20806823
TI  - [Late effect of treatment of nephroblastoma in patients treated in 1980-2001 in a
      single centre].
AB  - BACKGROUNDS: The aim of the study was to describe the late effects in a cohort of
      patients in long-term remission (> 5 years from end of treatment) diagnosed and
      treated for nephroblastoma at the single paediatric centre during 1980- 2001.
      PATIENTS AND METHODS: 151 patients were examined for renal function, lipid
      profile, sonography, echocardiography, exercise capacity and postural status. Age
      at diagnosis was 3.7 +/- 2.7 years, median 3.1, range 0.01-17.2 years. The cohort
      included 55% of women. Age in the study 19.4 +/- 5.8, median 19.6 years, range
      7.8-36 years. Anthracyclines (ATC) were administered to 25.9% of the cohort.
      Abdominal radiotherapy (RTA) was required in 34.2%. RESULTS: Creatinine clearance
      was on average 1.56 +/- 0.56 ml/s/1.73m2, (median 1.49 ml/s/1.73m2). Proteinuria
      was 0.18 +/- 0.30 g/24 h/m2, median 0.13 mg/24 h/m2. Three patients had
      proteinuria above 1 g/24 h with a normal glomerular filtration rate and s
      albumin. Hypertension was treated in 8.6% of patients (6% by pharmacotherapy).
      Increased diastolic blood pressure (DBP) and systolic blood pressure (SBP) was
      found in adolescents: DBP > 90 Torr was found in 10.2% of patients and SBP > 135
      Torr in 8.3%, all of them above the age of 15 years. ECHO did not reveal any
      pathology even in patients treated by ATC. Plasma cholesterol, LDL, HDL,
      triglycerides were outside the recommended range in two or more parameters in
      28.9% of the cohort. Lipoprotein Lp(a) > 500 mg.l(-1) (more than 200% higher than
      the upper limit) was found in 15.2%. Low peak oxygen consumption (VO2peak) was
      found in 40% of the cohort. Scoliosis (Sc) was anamnestically found in 46%.
      Prevalence of Sc according to the age of treatment has a similar trend as the
      reduced use of the RTA. Pulmonary function test showed a moderate increase in the
      functional residual capacity (the average Z-score of 1.35). VO2 peak correlates
      positively with the inspiratory capacity (p < 0.05). CONCLUSION: Based on the
      found pathologies and known risks, a schedule of late effect prevention and
      monitoring of patients in long-term NFB remission was established. It should
      include clinical examination, kidney function and blood pressure monitoring,
      sonographic and echocardiography examination, long-term physiotherapeutic care
      and prevention of cardiovascular diseases.

PMID- 20806824
TI  - [Changes in target volumes definition by using MRI for prostate bed radiotherapy
      planning--preliminary results].
AB  - BACKGROUNDS: Magnetic resonance imaging (MRI) is used quite routinely in
      radiotherapy treatment planning in the primary radiotherapy of prostate cancer as
      it provides more contrast imaging of soft tissues in the small pelvis than
      planning CT, thanks to which it allows more exact delineation of target volumes
      and thus the saving of organs at risk We tried to verify whether it is possible
      to use MRI by analogy in the planning of prostate bed radiotherapy. PATIENTS AND
      METHODS: Twentyone patients indicated for prostate bed radiotherapy were
      considered in this study. Here we present the preliminary results of 10 of them.
      Four patients were indicated for adjuvant, 6 for salvage radiotherapy. All the
      patients underwent, besides standard planning CT, MRI in the same position.
      Target volumes and organs at risk were delineated into CT,T1 and T2 MRI images -
      clinical target volume (CTV), planning target volume (PTV), urinary bladder and
      rectum. Based on the merging of images, the volumes delineated in MRI were copied
      into planning CT, where the evaluation was done. We evaluated the volumes of each
      structure, agreement in contouring with the help of the rate of union and
      intersection of the volumes and with Cohen's kappa, and 3D differences between
      volumes of CTV on CT, T1 and T2 MRI. RESULTS: Statistically, volumes of CTV and
      PTV are not significantly different. The volume of the rectum is significantly
      smaller on T1 and also T2 MRI images. The index of agreement (union/intersection)
      is statistically significantly different from 1 for CTV and PTV as well. Cohen's
      kappa indicates moderate agreement for CTV CT and T1, T1 and T2 MRI, fair
      agreement for CTV CT and T2 MRI, and substantial agreement for PTV. In the
      superior and superolateral direction, the CTV volume on MRI in the central plane
      is smaller on T1 and T2 images. In the area of seminal vesicles (SV) the cranial
      border is similar on CT and MRI. In the superoposterior direction, the volume of
      CTV is smaller on CT than on T1 and T2 MRI, which means, that seminal vesicles
      are delineated larger in the posterior direction on MRI (about 0.24cm on T1; by
      about 0.20cm on T2 images). In the posterior direction, there are no differences
      in CTV on CT and T1 while on T2 the CTV is larger (a difference of 0.29 cm). In
      the posterolateral direction, CTV is smaller on T1 MRI than on CT on both sides,
      on the right as well as on the left. CONCLUSION: Preliminary results suggest that
      clinical target volume defined with the help of MRI is shifted compared with CTV
      defined on planning CT. The agreement of CTV delineation by one radiation
      oncologist is moderate to fair and is similar to interobserver variability in the
      contouring of the prostate bed in the planning CT. MRI provides more contrast
      imaging of the anterior rectal wall, where we have confirmed the most differences
      in contouring. Moreover, it provides better imaging of local recurrences and
      seminal vesicles, where the most differences in our group of patients were seen
      in comparison with planning CT.

PMID- 20806825
TI  - [Metastatic breast cancer in 28 years old man].
AB  - BACKGROUNDS: Male breast cancer only makes up about 1% of all malignancies in the
      male population; the median age at time of diagnosis is 68 years. The treatment
      procedures used in clinical practice are those confirmed by studies on women.
      CASE: Presented is a case of a 28-year-old man with breast cancer in the fourth
      clinical stage. RESULTS: The patient was treated with the addition of trastuzumab
      to chemotherapy, radiotherapy, hormone treatment, with disease progression with
      lapatinib added to chemotherapy. 18 months after initiation of therapy, the
      patient died. CONCLUSION: Despite the increase in incidence, male breast cancer
      remains a rare diagnosis and treatment data are not confirmed in prospective
      randomized studies.

PMID- 20806826
TI  - [Nexavar clinical registry].

PMID- 20806827
TI  - Use of electronic medical records by ambulatory care providers: United States,
      2006.
AB  - OBJECTIVES: This report presents 2006 information on adoption of electronic
      medical records (EMRs) in five ambulatory care settings. Use of EMR systems
      within these settings is presented by selected provider characteristics. METHODS:
      Nationally representative estimates are from 2006 provider-based surveys,
      including the National Ambulatory Medical Care Survey (NAMCS), the National
      Hospital Ambulatory Medical Care Survey (NHAMCS), and the National Survey of
      Ambulatory Surgery (NSAS). RESULTS: In 2006, 62.4 percent of hospital-based
      ambulatory surgery centers (ASCs) reported using EMR systems, almost triple the
      percentage reported by freestanding ASCs (22.3 percent). EMR use by hospital
      emergency departments (EDs) was 46.2 percent, followed by hospital outpatient
      departments (OPDs) (29.4 percent) and office-based physicians (29.2 percent).
      Based on items collected in the 2006 NAMCS, NHAMCS, and NSAS, 18.6 percent of
      hospital-based ASCs, 14.0 percent of hospital EDs, and 10.5 percent of office
      based physicians had systems with similar features of a basic system, but only
      1.7 percent of hospital EDs and 3.1 percent of office-based physicians had
      systems with similar features of a fully functional system. Fully functional
      systems are a subset of basic systems. Physicians in practices with 11 or more
      physicians were most likely to use EMRs (46.5 percent), whereas physicians in
      solo practices were least likely to use EMRs (24.0 percent). Use of EMR systems
      was higher among physicians located in the West (42.3 percent) than in other
      regions of the country (23.5 percent to 29.3 percent). EMR use did not vary by
      neighborhood poverty level for any of the ambulatory providers studied. From 2001
      through 2005, EMR systems in hospital EDs increased by 47.2 percent. Use of EMRs
      among office-based physicians increased by 60.4 percent from 2001 through 2006.
      If those without EMR systems in 2006 with definite plans to install a system
      actually do so, 85.4 percent of hospital-based ASCs, 72.2 percent of EDs, 62.6
      percent of OPDs, 47.3 percent of freestanding ASCs, and 47.0 percent of
      physicians will be using EMR systems in 2009.

PMID- 20806828
TI  - Trends in health status and health care use among older men.
AB  - OBJECTIVES: This report examines trends in health status and risk factors, health
      care utilization, and health care expenditures among older men in the United
      States. METHODS: The estimates in this report are based on data from the National
      Vital Statistics System, National Health Interview Survey, National Health and
      Nutrition Examination Survey, National Health Care Surveys, Medicare Current
      Beneficiary Survey, and Current Population Survey. Trends in death rates,
      prevalence of chronic conditions, risk factors, vaccinations, health care
      utilization, and expenditures are summarized. Major differences in these
      indicators are described for older men and women and by age, race, and Hispanic
      origin. RESULTS: The difference in life expectancy between older men and women
      has narrowed since 1980, but a gap remains. Older men have lower hypertension and
      cholesterol levels and exercise regularly at higher rates than older women;
      however, the rates of obesity and cigarette smoking are similar in older men and
      women. Although health status has improved for all racial and ethnic groups,
      racial and ethnic disparities remain for many indicators. Older men and women
      have similar rates of hospital admissions and visits to emergency departments and
      physician offices.

PMID- 20806829
TI  - 2010 election gear-up: doctors 'show me' the effort.

PMID- 20806830
TI  - What we can learn from others.

PMID- 20806831
TI  - The Kirksville experience: where osteopathic medicine began.

PMID- 20806832
TI  - Moral and prudential considerations in adopting electronic medical records.
AB  - One might argue that beneficence entails a moral obligation for health care
      providers and systems to adopt electronic medical records (EMR). But this
      argument is thwarted because EMR systems are currently not required to meet
      existing standards of care for health care services. Yet using EMR systems may
      still be prudent if benefits of adoption significantly outweigh burdens. Future
      moral questions regarding EMR systems will shift from obligations of adoption to
      that of proper use.

PMID- 20806833
TI  - The eight steps to an effective employee termination policy.

PMID- 20806834
TI  - Pharmacological and physiological science is the essence of life itself.

PMID- 20806835
TI  - It's all a matter of taste: gustatory processing and ingestive decisions.
AB  - This paper reviews the physiology of taste processing and ingestive decisions.

PMID- 20806836
TI  - Acute lung injury and the acute respiratory distress syndrome: pathophysiology
      and treatment.
AB  - Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent
      a spectrum of acute respiratory failure with diffuse, bilateral lung injury and
      severe hypoxemia caused by non-cardiogenic pulmonary edema. Failure may be
      initiated by pulmonary or extrapulmonary insults (e.g., pneumonia, sepsis,
      trauma, aspiration) that increase alveolar epithelial endothelial permeability,
      flood alveoli, and reduce lung compliance. The only treatment proven to improve
      survival is mechanical ventilation using a 'lung protective strategy' with tidal
      volume =6 mL/kg predicted body weight. Although mortality can exceed 50%,
      survivors have a good prognosis for recovery of lung function.

PMID- 20806837
TI  - Use of human simulators to better teach the physiology and pharmacology of
      autonomic and cardiovascular drugs.

PMID- 20806838
TI  - Searching for new strategies for the pharmacological treatment of chronic pain.
AB  - Chronic pain is poorly managed and represents a huge unmet medical need that
      affects humans globally. The traditional multifaceted drug regimens for
      controlling chronic pain are marginally effective, produce highly variable
      results and display for the most parts unacceptable side effects. Research
      efforts over the last decade have identified peroxynitrite (PN) as a critical
      signaling molecule in the development of pain. Targeting PN is a novel evidence
      based approach to develop novel therapeutics for managing chronic pain.

PMID- 20806839
TI  - Vascular disease in pre-diabetes: new insights derived from systems biology.
AB  - In many cases vascular disease is present before the clinical onset of type 2
      diabetes, that is, during the pre-diabetic period when insulin levels are
      markedly increased. In pre-diabetes, microvascular dysfunction correlates with
      plasma insulin levels and not blood glucose. Here we discuss the concept that
      insulin, at levels found in pre-diabetes, contributes to microvascular disease in
      skeletal muscle by inhibiting the release of the vasodilator, adenosine
      triphosphate (ATP), from erythrocytes.

PMID- 20806840
TI  - Genetic disorders of ion channels.
AB  - Ion channels play important roles in numerous physiological processes, including
      the control of heart rate, propagation of the nerve impulse, and insulin
      secretion. Abnormal functioning of ion channels can cause disease. This article
      presents an overview of the diseases in humans that are a result of mutations in
      ion channels.

PMID- 20806841
TI  - Pharmacotherapeutic approach to the treatment of addiction: persistent
      challenges.
AB  - The sequence of pathophysiological responses to repeated self-administration of
      addictive compounds is briefly described, as are prospects for development of
      drugs for addiction and some of those currently available. It is noted that the
      varying vulnerability of individuals to addictions creates ethical concerns
      regarding the application of drug abuse pharmacotherapies as they become more
      efficacious. It is noted further that relapse remains the most persistent
      challenge in the treatment of addictions.

PMID- 20806842
TI  - Tibial shock measured during the fencing lunge: the influence of footwear.
AB  - Fencing is a high-intensity sport involving dynamic movements such as the lunge
      exposing the musculoskeletal system to high impact forces, which emphasises the
      importance of the shock attenuating properties of footwear as a factor in the
      prevention of injury. The aim of this study was to investigate the magnitudes of
      the transient axial impact shock experienced at the tibia between traditional
      fencing shoes and standard athletic footwear during the impact phase of the
      fencing lunge. Peak tibial shock was measured in 19 male fencers in 4 different
      footwear conditions using an accelerometer placed on the distal aspect of the
      tibia. The standard footwear (11.08 g and 8.75 g for squash and running shoe,
      respectively) resulted in significant (p < 0.01) reductions in peak impact shock
      in comparison to the traditional fencing shoes (15.93 g and 13.97 g for the
      Adidas and Hi-Tec shoe, respectively). No significant differences were found
      between the running and squash shoes (p = 0.09) or between the fencing shoes (p =
      0.48). The documented reduction in impact shock found suggests that running or
      squash specific footwear may reduce overuse injury occurrence, indicating that
      there is justification for a re-design of fencing shoes.

PMID- 20806843
TI  - Biomechanical analysis of the penalty-corner drag-flick of elite male and female
      hockey players.
AB  - The aim of this study was to analyse the kinematic sequencing in the penalty
      corner drag-flicks of elite male and female field hockey players of international
      calibre. Thirteen participants (one skilled male drag-flicker and six male and
      six female elite players) participated in the study. An optoelectronic motion
      analysis system was used to capture the drag-flicks with six cameras, sampling at
      250 Hz. Select ground reaction force parameters were obtained from a force
      platform which registered the last support of the front foot. Twenty trials were
      captured from each subject. Both player groups showed significantly (p < 0.05)
      smaller ball velocity at release, peak angular velocity of the pelvis, and
      negative and positive peak angular velocities of the stick than the skilled
      subject. Normalised ground reaction forces of the gender groups were also smaller
      than that of the skilled drag-flicker. By comparing these players we established
      that the cues of the skill level are a wide stance, a whipping action (rapid back
      lift) of the stick followed by an explosive sequential movement of the pelvis,
      upper trunk and stick.

PMID- 20806844
TI  - Reliability and variability of day-to-day vault training measures in artistic
      gymnastics.
AB  - Inter-day training reliability and variability in artistic gymnastics vaulting
      was determined using a customised infra-red timing gate and contact mat timing
      system. Thirteen Australian high performance gymnasts (eight males and five
      females) aged 11-23 years were assessed during two consecutive days of normal
      training. Each gymnast completed a number of vault repetitions per daily session.
      Inter-day variability of vault run-up velocities (at -18 to -12 m, -12 to -6 m, 
      6 to -2 m, and -2 to 0 m from the nearest edge of the beat board), and board
      contact, pre-flight, and table contact times were determined using mixed
      modelling statistics to account for random (within-subject variability) and fixed
      effects (gender, number of subjects, number of trials). The difference in the
      mean (Mdiff) and Cohen's effect sizes for reliability assessment and intra-class
      correlation coefficients, and the coefficient of variation percentage (CV%) were
      calculated for variability assessment. Approach velocity (-18 to -2m, CV = 2.4
      7.8%) and board contact time (CV = 3.5%) were less variable measures when
      accounting for day-to-day performance differences, than pre-flight time (CV =
      17.7%) and table contact time (CV = 20.5%). While pre-flight and table contact
      times are relevant training measures, approach velocity and board contact time
      are more reliable when quantifying vaulting performance.

PMID- 20806845
TI  - The effects of target distance on pivot hip, trunk, pelvis, and kicking leg
      kinematics in Taekwondo roundhouse kicks.
AB  - The study purpose was to investigate the effects of target distance on pivot hip,
      trunk, pelvis, and kicking leg movements in Taekwondo roundhouse kick. Twelve
      male black-belt holders executed roundhouse kicks for three target distances
      (Normal, Short, and Long). Linear displacements of the pivot hip and orientation
      angles of the pelvis, trunk, right thigh, and right shank were obtained through a
      three-dimensional video motion analysis. Select displacements, distances, peak
      orientation angles, and angle ranges were compared among the conditions using one
      way repeated measure ANOVA (p < 0.05). Several orientation angle variables
      (posterior tilt range, peak right-tilted position, peak right-rotated position,
      peak left-rotated position, and left rotation range of the pelvis; peak
      hyperextended position and peak right-flexed position of the trunk; peak flexed
      position, flexion range and peak internal-rotated position of the hip) as well as
      the linear displacements of the pivot hip and the reach significantly changed in
      response to different target distances. It was concluded that the adjustment to
      different target distances was mainly accomplished through the pivot hip
      displacements, hip flexion, and pelvis left rotation. Target distance mainly
      affected the reach control function of the pelvis and the linear balance function
      of the trunk.

PMID- 20806846
TI  - The effects of postseason break on stabilometric performance in female volleyball
      players.
AB  - Ankle sprain is a common injury in volleyball. Poor stabilometric performance
      (SP) is associated with high risks of sustaining ankle sprain. Balance training
      can improve SP and reduce ankle sprain, but no research has studied the effects
      of detraining on SP in highly trained athletes. The purpose of this study was to
      determine the effects of one-month postseason break on SP in female volleyball
      players. Eleven NCAA female volleyball players participated in two eye-closed
      single-leg stance tests before and after a one-month postseason break. Stance
      time, center of pressure (COP) area, COP standard deviation, and COP mean
      velocity were assessed during the tests. During the postseason break, subjects
      conducted self-selected exercise and the average training duration was 87% lower
      compared to the competition season. Subjects demonstrated significant increases
      in anterioposterior (A/P) COP standard deviation (1.6 +/- 0.4 vs. 1.8 +/- 0.4 cm,
      p = 0.05), mediolateral (M/L) COP velocity (6.5 +/- 1.5 vs. 7.1 +/- 1.3 cm/s, p =
      0.05), and overall COP velocity (10.1 +/- 2.0 vs. 11.6 +/- 1.9 cm/s, p = 0.02)
      after postseason break. SP decreased in highly trained female volleyball players
      after one-month postseason break. The decrease in SP indicated a possible
      increased risk for ankle sprain injury.

PMID- 20806847
TI  - Mechanics of pole vaulting: a review.
AB  - A good understanding of the mechanics of pole vaulting is fundamental to
      performance because this event is quite complex, with several factors occurring
      in sequence and/or in parallel. These factors mainly concern the velocities of
      the vaulter-pole system, the kinetic and potential energy of the vaulter and the
      strain energy stored in the pole, the force and torque applied by the athlete,
      and the pole design. Although the pole vault literature is vast, encompassing
      several fields such as medicine, sports sciences, mechanics, mathematics, and
      physics, the studies agree that pole vault performance is basically influenced by
      the energy exchange between the vaulter and pole. Ideally, as the athlete clears
      the crossbar, the vaulter mechanical energy must be composed of high potential
      energy and low kinetic energy, guaranteeing the high vertical component of the
      vault. Moreover, the force and torque applied by the vaulter influences this
      energy exchange and these factors thus must be taken into consideration in the
      analysis of performance. This review presents the variables that influence pole
      vault performance during the run-up, take-off, pole support, and free flight
      phases.

PMID- 20806848
TI  - Prejudice against international students: the role of threat perceptions and
      authoritarian dispositions in U.S. students.
AB  - International students provide a variety of benefits to higher education
      institutions within the United States (J. J. Lee, 2007; J. J. Lee & C. Rice,
      2007). Despite these benefits, many international students experience prejudice
      and discrimination by American students. The purpose of the present study was to
      examine several potential predictors of prejudice against international students:
      perceptions of international students as symbolic and realistic threats, right
      wing authoritarianism, and social dominance orientation. A simultaneous
      regression analysis that the authors based on 188 students at a Southwestern
      university revealed that perceptions of symbolic and realistic threats and social
      dominance orientation were each positive and significant predictors of prejudice.
      Mediation analyses suggested that the effects of right-wing authoritarianism on
      prejudice is fully mediated through perceived symbolic threat and partially
      mediated by realistic threat.

PMID- 20806849
TI  - Time management training and perceived control of time at work.
AB  - The purpose of the present study was to examine the effects of time management
      training, which was based on psychological theory and research, on perceived
      control of time, perceived stress, and performance at work. The authors randomly
      assigned 71 employees to a training group (n = 35) or a waiting-list control
      group (n = 36). As hypothesized, time management training led to an increase in
      perceived control of time and a decrease in perceived stress. Time management
      training had no impact on different performance indicators. In particular, the
      authors explored the use and the perceived usefulness of the techniques taught.
      Participants judged the taught techniques as useful, but there were large
      differences concerning the actual use of the various techniques.

PMID- 20806850
TI  - The effect of attachment insecurity in the development of eating disturbances
      across gender: the role of body dissatisfaction.
AB  - The present study examined the effects of insecure attachment on the development
      of negative body image as a contributing factor to the development of disturbed
      eating patterns in male and female university students. Participants were
      nonclinical male (n = 100) and female (n = 381) university students.
      Administering self-report questionnaires, the authors assessed demographic
      information (gender, age), anthropometric data (Body Mass Index [BMI], age),
      romantic attachment (ECRS-R; R. C. Fraley, N. G. Waller, & K. A. Brennan, 2000),
      body dissatisfaction (BSQ), and disturbed eating (EAT-26). The authors found body
      dissatisfaction to fully mediate the relationship between attachment anxiety and
      disordered eating in women. Body dissatisfaction mediated anxious attachment and
      dieting in men. In addition, attachment avoidance had a direct impact on eating
      behaviors for both genders, without the mediation of any variables measured in
      this study. The findings of the present study suggest that the anxiety and
      avoidance dimensions of attachment insecurity affect eating behaviors
      differently, and the effects are different across genders. The authors discuss
      results in the context of therapeutic interventions design.

PMID- 20806851
TI  - Wording effect leads to a controversy over the construct of the social dominance
      orientation scale.
AB  - Most investigations of individuals' social dominance orientation (SDO) have used
      the 16-item SDO scale developed by F. Pratto, J. Sidanius, L. M. Stallworth, and
      B. F. Malle (1994). The scale's authors believed it to be a unidimensional scale,
      but other researchers have found the scale has 2 or more factors. The present
      authors proposed a new hypothesis: The controversy of the scale structure was
      related to the wording effect of the scale. Based on a sample of Americans,
      Canadians, and Chinese, the present study indicated that what the scale measured
      was not only 1 trait of SDO, but also a negative-wording effect factor and that
      the scale structure was invariant across the 3 cultural groups. The existence of
      a wording effect reminds us to be cautious of the construct validity of the scale
      and interpretations of results.

PMID- 20806853
TI  - [Supracricoid partial laryngectomy for the therapeutic outcomes of laryngeal
      cancer].
AB  - OBJECTIVE: To evaluate the therapeutic effect of supracricoid partial
      laryngectomy(SCPL). METHOD: A retrospective analysis of the clinical data of 24
      patients undergoing laryngeal carcinoma (including 5 senile patients). In those
      patients, 14 were glottic cancer, 9 were supraglottic cancer,and 1 were
      transglottic cancer. Fourteen cases underwent cricohyoidoepiglottopexy, and 10
      cases treated with cricohyoidopexy. RESULT: In this study, 3 years and 5 years
      survival rates were 91.7% and 78.6%. The decannulation rate was 91.7%. All the
      patients resumed physiologic swallowing. CONCLUSION: Supracricoid partial
      laryngectomy for selected laryngeal cancer is feasible, and also for senile
      patients. The patients can gain satisfied survival rate and physiologic function.

PMID- 20806852
TI  - [Clinical analysis of 28 patients with chronic rhino-sinusitis only characterized
      olfactory disorders].
AB  - OBJECTIVE: To analyses the clinical characteristics of 28 chronic rhino-sinusitis
      patients only characterized olfactory disorders. METHOD: Twenty-eight patients
      who have only olfactory disorder were diagnosed chronic rhino-sinusitis, among
      which 16 patients accepted intranasal budesonide for 15 days. All patients
      accepted CT scan, T&T test and olfactory event-related potentials test before and
      after treatment. RESULT: (1) No difference was found between 21 patients ( < or =
      12 months) and 7 patients (>12 months) (P > 0.05), significant difference was
      found between maxillary sinus,ethmoid sinus and frontal sinus, sphenoid sinus in
      CT scan (P < 0.01). (2) Olfactory function improves after treatment (P < 0.01).
      Significant difference is found between 12 patients ( < or =12 months) and 4
      patients (P < 0.01). CONCLUSION: (1) Chronic rhino-sinusitis patients who have
      only olfactory disorder were found; (2) Intranasal budesonide treatment could
      improve olfactory functions of chronic rhino-sinusitis' patients.

PMID- 20806854
TI  - [Primary, study of miRNA expression patterns in laryngeal carcinoma by
      microarray].
AB  - OBJECTIVE: To detect the expression of microRNAs (miRNAs) in laryngeal carcinoma
      and adjacent normal tissue using microarray, and to discuss the relationship
      between miRNAs and laryngeal carcinoma. METHOD: miRNA were extracted from 8 cases
      of laryngeal cancer tissue and its adjacent normal tissue. miRNA identification
      were performed by microarray of miRNA hybridization and cluster analysis was used
      with Significance Analysis of Microarrays (SAM, version 2.1) and Cluster 3.0
      software. miRNA were confirmed by real time quantification RT-PCR with RNA
      tailing and primer extension. RESULT: Totally 47 different miRNAs were found
      expressed in laryngeal cancer, with 23 of miRNA expression were up-regulated and
      24 of miRNA expression were down-regulated. The expression of miR-1, miR-486-5p,
      miR-206, miR-487a,miR-375, miR-422a, miR-144, miR-384, miR-378, miR-133a were
      down-regulated by 5 multiple and while expression of miR-93, miR-31, miR-20b were
      up-regulated by 3 multiple. There are 5 miRNA clusters with coexpression in
      laryngeal cancer tissue and located on chromosome 8, 13, 14, 18 and X. Moreover,
      RT-PCR analysis demonstrated that there was no significantly difference of miRNA
      expression between microarray and RT-PCR. CONCLUSION: The different expression of
      miRNA may play an important role in the pathogenesis and development of laryngeal
      cancer.

PMID- 20806855
TI  - [Application of mitomycin in laryngeal surgery].
AB  - OBJECTIVE: To investigate the application of mitomycin in laryngeal surgery.
      METHOD: Retrospective analysis of the clinical data of 48 patients who had vocal
      cord lesion involving anterior commissure. The treatment of 30 patients treated
      with microsurgery and external application of mitomycin, while that of the others
      were only done with microsurgery. RESULT: Among the 30 patients who were treated
      with microsurgery and mitomycin, only 2 patients of which showed slight adhesion
      of anterior commissure after surgery. While in the group of microsurgery, there
      were 6 patients who had adhesion of anterior commissure adhesion after surgery.
      CONCLUSION: Mitomycin could prevent vocal adhesion after laryngeal surgery.

PMID- 20806856
TI  - [Diagnosis and surgical treatment of parathyroid carcinoma].
AB  - OBJECTIVE: To evaluate the diagnosis and surgical treatment of parathyroid
      carcinoma (PTC). METHOD: Clinical data of 4 PTC cases were analyzed
      retrospectively. Four patients all had palpable neck mass. Calcium level was
      (3.25 +/- 0.53) mmol/L, and PTH level was (1210.25 +/- 528.72) ng/L. Frozen
      section established diagnosis in only one case. Routine histopathology combined
      with immunohistochemistry established the diagnosis in 3 patients.
      Parathyroidectomy and ipsilateral subtotal thyroidectomy was performed in 3
      patients; endoscopic parathyroidectomy was performed in one patient. RESULT: They
      were followed up for 8-60 months, Calcium level and PTH level were normal. No
      tumor recurrence and metastasis. CONCLUSION: The diagnosis of PTC is difficult
      before operation. Routine blood examinations: blood calcium, blood PTH; Imaging
      examinations: ultrasonography, CT are helpful to diagnosis. Frozen biopsy is not
      satisfactory. An initial en bloc resection of tumor and adjacent structures
      contributes most to the prognosis.

PMID- 20806857
TI  - [Clinical analysis on 368 children cases with tracheobronchial foreign body].
AB  - OBJECTIVE: To investigate the clinical pathological features of children
      tracheobronchial foreign bodies and to improve diagnosis and treatment. METHOD: A
      retrospective study 368 children cases with tracheobronchial foreign bodies in
      our hospital. Each patient was analyzed for age, sex, nature,complication and
      location of the foreign body, results of bronchoscopic removal and presence of
      foreign bodies in the airways. Among this cases, three of them coughed out the
      foreign body before operation; two of them failed to be operated for serious
      complication, others were conducted by rigid bronchoscopy and bronchoscopic
      removal with general anaesthesia. RESULT: Three children of 368 coughed out the
      foreign body before operation; 4 children of them were dead for the long
      heartbeat respiratory arrest and deep coma; 2 children of them suffered form
      hypoxic ischemic encephalopathy and epilepsy; others were successfully taken out
      by operation. CONCLUSION: For the diagnosis of children cases with
      tracheobronchial foreign bodies, it is very important to collect the detailed
      history of foreign body inhalation, physical examination and careful analysis on
      the findings from chest radiographs or CT scan.

PMID- 20806858
TI  - [The impact of nasal obstruction on OSAHS].
AB  - OBJECTIVE: To evaluate the impact of nasal obstruction on OSAHS. METHOD: One
      hundred and twenty cases of OSAHS with or without nasal obstruction were analyzed
      by Hypno PTT(PTT)and Mallampati score (MS); Acoustic rhinometry was measured in
      all 120 cases. RESULT: A significant correlation was found between the MS and the
      AHI measured during the sleep (r = 0.266, P < 0.01). The relative risk of OSAHS
      with a MS of III or IV in the whole group was 1.96, and 2.46 in cases with nasal
      obstruction. CONCLUSION: A high MS represents a predisposing factor for OSAHS,
      especially in which associated with nasal obstruction.

PMID- 20806859
TI  - [Comparative analysis chest CT 3D reconstruction and esophagus barium swallow in
      esophagus foreign body].
AB  - OBJECTIVE: To compare the diagnosis and therapeutic between chest computed
      tomography three-dimensional reconstruction and esophagus barium swallow in
      esophagus foreign body. METHOD: retrospective analyze one hundred and thirty six
      patients who suffered from esophagus foreign body in our hospital, 97 cases using
      esophagus barium swallow, 17 cases using chest computed tomography three
      dimensional reconstruction, 15 cases using both. RESULT: The patients who showed
      positive of esophagus foreign body in esophagus barium swallow or chest computed
      tomography three-dimensional reconstruction, 91.8% (89/97) cases or 88.2% (15/17)
      cases found esophagus foreign bodies finally. All cases successfully took out the
      esophagus foreign bodies only through one operation which used chest computed
      tomography three-dimensional reconstruction as primary examination, while only
      91.0% for those used esophagus barium swallow as primary examination. CONCLUSION:
      Both chest computed tomography three-dimensional reconstruction and esophagus
      barium swallow showed high diagnostic efficiency on esophagus foreign body. Chest
      computed tomography three-dimensional reconstruction had advantages in patients
      with one of following conditions: (1) esophagus foreign body located in the
      middle of the esophagus, especially complicated with esophagus perforation; (2)
      with fever, high white blood count, presence of abscess surrounding the esophagus
      was suspected; (3) with dyspnea; (4) with a history of esophagus foreign body
      longer than 5 days; (5) younger than 6 years old.

PMID- 20806860
TI  - [Manifestations and management of malignant lymphoma in head and neck].
AB  - OBJECTIVE: To explore the clinical feature, treatment and prognosis of malignant
      lymphoma in head and neck. METHOD: One hundred and sixteen cases with malignant
      lymphoma in head and neck were retrospectively analyzed. The predilection site
      was most in head and neck (39.7%), followed by palate and tonsil (23.3%). The
      clinical symptoms was different based on different location, painless mass in
      neck was mostly seen. The misdiagnosis rate is 37.1%. The treatment measures
      mainly included combined modality therapy and chemotherapy. RESULT: Among 98
      cases, of stage I and II, the survival time of 51 cases was more than one year,
      24 cases were more than 3 years, 12 cases were more than 5 years. Eleven patients
      were lost to follow-up. Among 18 cases, of stage III and IV, 3 patients was lost
      to follow-up, the other 15 cases were dead after half a year. CONCLUSION:
      clinical feature of malignant lymphoma in head and neck is nonspecific and
      complicated, misdiagnosis most easily occurs. Biopsy is the most valuable in the
      diagnosis of malignant lymphoma. Combined modality therapy is the mainstay of
      treatment in malignant lymphoma. The clinical stage classification is important
      for prognosis.

PMID- 20806861
TI  - [The relationship between extend types and distant metastasis of nasopharyngeal
      carcinoma].
AB  - OBJECTIVE: To explore the relationship between extend types and distant
      metastasis of nasopharyngeal carcinoma (NPC). METHOD: Retrospective analyze 260
      patients with nasopharyngeal carcinoma, among which 162 cases were distant
      metastasis (metastasis group) and 98 cases were neither distant metastasis nor
      recurrence (disease-free group) over 5 years after radiotherapy. All these
      patients were staged depending on CT or MRI image before treatment and divided
      into local-regional type(T(1-2)N(0-1)) for 36 cases and upward invasion type (T(3
      4)N(0-1)) for 68 cases and downward invasion type (T(1-2)N(2-3)) for 75 cases and
      mixed type (T(3-4)N(2-3)) for 81 cases. The differences between two groups was
      analyzed using Chi-square test. RESULT: The local-regional type and upward
      invasion type was 25.3% for the metastasis group and 64.3% for the disease-free
      group. The downward and mixed invasion was 74.7% for the metastasis group and
      35.7% for the disease-free group. The rate(proportion) of N(2-3) was
      significantly higher in metastasis group than in disease-free group with limited
      extension (84.4% vs. 33.3%, P < 0.01). The rates(proportion) of N(0-1) and N(2-3)
      were also significantly higher in metastasis group than in disease-free group
      with severity extension (T(3-4) (60% vs. 36.1% and 68.4% vs. 40%, P < 0.01).
      CONCLUSION: The extent of cervical lymph node metastases is one of the most
      important factors of NPC with distant metastasis, severity extension of primary
      disease should also be in consideration. Even the limitations of primary disease,
      once cervical lymph node metastasis occurs, the risk of distant metastasis is
      significantly increased.

PMID- 20806862
TI  - [Tumorectomy by trans-oral approach of macrosis benign neoplasms in
      parapharyngeal space (reports of 6 cases)].
AB  - OBJECTIVE: To discuss the feasibility of tumorectomy by transoral approach of
      macrosis benign neoplasms in parapharyngeal space. METHOD: Retrospective analyze
      6 patients of macrosis benign neoplasms in parapharyngeal space from January 2005
      to May 2008, and all neoplasms were removed by transoral approach. Tracheotomy
      was performed in 3 cases. RESULT: The neoplasms were all removed completely and
      successfully, and postoperative recovery were good and no complications were
      found. There were 2 cases of neurofibroma, 2 cases of neurilemmoma, 2 cases of
      pleomorphic adenoma. There are no recurrence after 20 months to 5 years follow
      up. CONCLUSION: Preoperative imaging examination is very important for diagnosis
      and treatment of benign neoplasm in parapharyngeal space, which is especially
      helpful to understand the scope of the tumor, and the relationship with carotid
      artery and vein. On this basis, it is feasible to select the appropriate cases to
      resect huge benign neoplasm in parapharyngeal space.

PMID- 20806863
TI  - [Effect of H3R agonist, IMETIT on allergic rhinitis in guinea pigs].
AB  - OBJECTIVE: To discuss the treatment of H3R agonist, IMETIT, on the allergic
      rhinitis(AR) ,and the influence to mRNA of Substance P(SP) and Substance P
      Receptor (SP-R) in AR model of guinea pigs. METHOD: The severity of AR was
      assessed by allergic symptoms (sneezing, nasal rubbing and nose blocking). The
      changes in the nasal mucosa were studied by pathological methods. The expression
      of SP positive cell was detected by immunohistochemistry, and the expression of
      SP-R mRNA was detected by reverse transcriptive polymerase chain reaction (RT
      PCR). RESULT: Histamine H3R agonists, IMETIT can effectively improve the AR
      symptoms, sneezing, nasal itching, nasal congestion, reduce the pathological
      changes in the nasal mucosa, cut down the SP secretion and SP-R mRNA expression.
      CONCLUSION: Histamine H3R agonist, IMETIT can effectively relieve the symptoms of
      AR in guinea pigs, which is related to reducing SP secretion and SP-R mRNA
      expression.

PMID- 20806864
TI  - Understanding the sustainable growth rate (SGR) fiasco.

PMID- 20806865
TI  - Health management program helps patients with chronic disease.

PMID- 20806867
TI  - Computed tomography features of middle ear cholesteatoma in dogs.
AB  - We describe the computed tomography (CT) findings in 11 dogs with middle ear
      cholesteatoma. The cholesteatoma appeared as an expansile tympanic cavity mass
      with a mean attenuation value of 55.8 +/- 4.2 Hounsfield units. There was no
      appreciable contrast enhancement of the tympanic bulla contense but ring
      enhancement was seen in four dogs. Due to the slow progressive growth, the lesion
      causes severe bone changes at the contour of the tympanic bulla, including
      osteolysis, osteoproliferation and osteosclerosis, expansion of the tympanic
      cavity, and sclerosis or osteoproliferation of the ipsilateral temporomandibular
      joint and paracondylar process. Cholesteatoma can cause lysis of the petrosal
      part of the temporal bone, leading to intracranial complications. Although not
      definitive, CT provides useful information for distinguishing a middle ear
      cholesteatoma from otitis media and neoplasia. In otitis media, enlargement of
      the tympanic cavity is not routinely observed. In tumors that primarily affect
      the middle or inner ear, the predominant signs are lysis of the contour of the
      tympanic bulla or the petrosal part of the temporal bone, soft tissue swelling
      around the middle ear and marked contrast enhancement. In tumors that arise from
      the external ear, a soft tissue mass is visible within the external acusticus
      meatus, and the middle ear is only involved secondarily.

PMID- 20806866
TI  - Normal canine brain maturation at magnetic resonance imaging.
AB  - The normal neonatal canine brain exhibits marked differences from that of the
      mature brain. With development into adulthood, there is a decrease in relative
      water content and progressive myelination; these changes are observable with
      magnetic resonance imaging (MRI) and are characterized by a repeatable and
      predictable time course. We characterized these developmental changes on common
      MRI sequences and identified clinically useful milestones of transition. To
      accomplish this, 17 normal dogs underwent MRI of the brain at various times after
      birth from 1 to 36 weeks. Sequences acquired were T1-weighted (T1W), T2-weighted
      (T2W), fluid attenuated inversion recovery, short tau inversion recovery, and
      diffusion weighted imaging sequences. The images were assessed subjectively for
      gray and white matter relative signal intensity and results correlated with
      histologic findings. The development of the neonatal canine brain follows a
      pattern that qualitatively matches that observed in humans, and which can be
      characterized adequately on T1W and T2W images. At birth, the relative gray
      matter to white matter signal intensity of the cortex is reversed from that of
      the adult with an isointense transition at 3-4 weeks on T1W and 4-8 weeks on T2W
      images. This is followed by the expected mature gray matter to white matter
      relative intensity that undergoes continued development to a mostly adult
      appearance by 16 weeks. On the fluid attenuated inversion recovery sequence, the
      cortical gray and white matter exhibit an additional signal intensity reversal
      during the juvenile period that is due to the initial high relative water content
      at the subcortical white matter, with its marked T1 relaxation effect.

PMID- 20806868
TI  - MRI features of gastrocnemius musculotendinopathy in herding dogs.
AB  - Pelvic limb lameness that was localized clinically to the lateral gastrocnemius
      head was observed in dogs without history of trauma. The aim of this
      retrospective study was to describe magnetic resonance imaging (MRI) findings of
      this condition. Nine dogs were identified, eight Border Collies and one
      Australian Shepherd. They all had chronic pelvic limb lameness; no signs of joint
      effusion or instability were present. In MR images there was high signal
      intensity in the lateral head of the gastrocnemius muscle around the sesamoid
      bone in T2-weighted, T2*-weighted, and STIR images and an iso- to mildly
      hyperintense signal in T1-weighted images with marked contrast enhancement. The
      abnormal signal intensity most likely represents a myotendinous strain. The breed
      affiliation to Border Collies is striking, and a relation to biomechanical forces
      or motion pattern may be possible. Except for the dog with the most extensive
      lesion all dogs had an excellent outcome.

PMID- 20806869
TI  - Radiographic appearance of confirmed pulmonary lymphoma in cats and dogs.
AB  - Herein we describe the thoracic radiographic appearance of confirmed pulmonary
      lymphoma. Patients with thoracic radiographs and cytologically or histologically
      confirmed pulmonary lymphoma were sought by contacting American College of
      Veterinary Radiology members. Seven cats and 16 dogs met the inclusion criteria,
      ranging in age from 4 to 15 years. Method of diagnosis was via ultrasound-guided
      cytology (four), surgical biopsy (two), ultrasound-guided biopsy (one), and
      necropsy (16). Radiographic findings varied but ranged from normal (one) to
      alveolar (six) and/or unstructured interstitial infiltrates (11), nodules and/or
      masses (eight), and bronchial infiltrates (four). Additional thoracic
      radiographic findings included pleural effusion and lymphadenopathy. The results
      of this evaluation indicate a wide variability in thoracic radiographic
      abnormalities in cats and dogs with pulmonary lymphoma.

PMID- 20806870
TI  - Direct magnetic resonance arthrography of the canine shoulder.
AB  - Our goal was to evaluate the ability of three magnetic resonance arthrography
      (MRA) techniques to improve visualization of soft tissue stabilizing components
      of the canine shoulder. The optimum concentration of gadolinium (gadodiamide) for
      MRA was determined by imaging seven individual shoulders with one of seven
      dilutions of 0.5 mol/l gadodiamide in saline; (1:100, 1:400, 1:800, 1:1000,
      1:1200, 1:1400, and 1:1600). For this, sagittal and dorsal T1-weighted fat
      saturation (T1WFS) images were used. The 1:1200 dilution of gadolinium was
      determined to be the optimum concentration as it provided adequate contrast to
      distinguish supporting joint structures without obscuring the edges of those
      structures. Sagittal, dorsal, and transverse MRA images were then acquired in
      nine cadaver shoulders using T1WFS with gadolinium, proton density fat saturation
      (PDFS) with gadolinium, and PDFS with saline. Descriptive comparisons were made
      among techniques. When gadolinium was compared with saline as a contrast medium,
      gadolinium provided greater contrast against underlying soft tissues, thereby
      enhancing tendon and ligament conspicuity. When T1WFS and PDFS gadolinium
      sequences were compared, minor differences were noted. The interface between
      tissue and fluid was sharper and more distinct in PDFS images. MRI arthrography
      has promise as a tool for the diagnosis of canine soft tissue shoulder injury.
      MRA may be most useful when trauma to the biceps tendon, lateral glenohumeral
      ligament, or medial glenohumeral ligament is suspected.

PMID- 20806871
TI  - Computed tomography characteristics of canine tracheobronchial lymph node
      metastasis.
AB  - Tracheobronchial lymph node evaluation is critical for accurate staging of canine
      thoracic neoplasia and is more accurately achieved with computed tomography (CT)
      than radiography. Thoracic CT scans of 18 canine patients with known
      tracheobronchial lymph node histopathology and 10 clinically normal dogs were
      compared to establish if enlargement or contrast enhancement pattern correlated
      with metastatic status. Absolute lymph node size and three anatomically
      normalized lymph node ratios were significantly correlated with metastasis or
      severe granulomatous lymphadenitis (P < 0.0003). Transverse maximum lymph node
      diameter of 12 mm or lymph node to thoracic body ratio of 1.05 are proposed
      cutoffs, above which metastatic involvement is very likely; however, only minimal
      accuracy was gained with normalized ratios. Lymph node contrast enhancement
      pattern was also significantly correlated to disease. A heterogenous and/or ring
      pattern was related to metastatic disease (P = 0.03). Recommended protocol for CT
      examination of the tracheobronchial lymph nodes is 1-1.5 mm slices and intervals,
      intravenous contrast, and control of respiratory motion.

PMID- 20806872
TI  - MRI features of metacarpo(tarso)phalangeal region lameness in 40 horses.
AB  - Lameness originating from the metacarpo(tarso)phalangeal (MP) joint has a
      significant effect on the use and athletic competitiveness of a horse. The
      identification of the cause of lameness originating from the MP joint can be
      challenging, given the limitations of radiography, ultrasonography, and nuclear
      scintigraphy. Our purpose was to describe the injury types and incidence in
      magnetic resonance imaging (MRI) studies from 40 horses with lameness
      attributable to the MP joint region where it was not possible to reach a
      clinically plausible diagnosis using other imaging modalities. Horses were
      examined in a 1.5 T magnet (Siemens Medical Solutions) under general anesthesia.
      The frequency of occurrence of MR lesions was subchondral bone injury (19),
      straight or oblique distal sesamoidean desmitis (13), articular cartilage injury
      and osteoarthritis (eight), suspensory branch desmitis (seven), osteochondral
      fragmentation (seven), proximal sesamoid bone injury (seven), inter-sesamoidean
      desmitis (four), deep digital flexor tendonitis (four), collateral desmitis
      (three), superficial digital flexor tendonitis (two), enostosis-like lesions of
      the proximal phalanx or MCIII (two), desmitis of the palmar annular ligament
      (one), desmitis of the proximal digital annular ligament (one), and dystrophic
      calcification of the lateral digital extensor tendon (one). Twenty-five horses
      had multiple MR abnormalities. MRI provided information that was complementary to
      radiography, ultrasonography, and nuclear scintigraphy and that allowed for a
      comprehensive evaluation of all structures in the MP joint region and a diagnosis
      in all 40 horses.

PMID- 20806873
TI  - Influence of the chemical shift artifact on measurements of compact bone
      thickness in equine distal limb MR images.
AB  - The effect of the chemical shift artifact, resulting from misregistration or
      phase cancellation at the interface between compact and trabecular bone, on
      apparent bone thickness was quantified in six isolated equine limbs. Sagittal T1
      weighted spin echo (SE) and in-phase three-dimensional spoiled gradient echo
      (SPGR) images were acquired twice with a 1.5 T magnetic resonance (MR) unit,
      switching the frequency encoding direction between acquisitions. Out-of-phase
      SPGR images were also obtained. MR images with different frequency encoding
      directions were compared with each other and to radiographs made from
      corresponding 3-mm-bone sections. Compact bone thickness was significantly
      different when comparing images acquired with different frequency encoding
      directions for both SE and SPGR sequences. Significant differences were
      identified in the frequency but not the phase encoding direction when
      measurements of compact bone in MR images were compared with measurements
      obtained from thin section radiographs for the majority of surfaces studied (P <
      0.05). Correction of MR measurements with the calculated chemical shift abolished
      these differences (P > 0.05). Measurements of compact bone from out-of-phase SPGR
      sequences were significantly different than from in-phase sequences (P < 0.001)
      with out-of-phase measurements greater than in-phase measurements by an average
      of 0.38mm. These results indicate that the chemical shift artifact results in
      errors in MR evaluation of compact bone thickness when measurements are performed
      in the frequency encoding direction or in out-of-phase images. For better
      accuracy, measurements should be performed parallel to the phase encoding
      direction and avoiding out-of-phase gradient echo sequences.

PMID- 20806874
TI  - Clinical application of Patlak plot CT-GFR in animals with upper urinary tract
      disease.
AB  - Glomerular filtration rate (GFR), an important parameter of renal function, is
      difficult to assess clinically. Serum creatinine and blood urea nitrogen
      measurements lack sensitivity, whereas radionuclide determination of GFR is not
      always available and requires postinjection patient isolation. GFR can be
      determined using computed tomography (CT), most commonly via Patlak plot
      analysis. Four adult cats, two adult dogs, and a foal underwent abdominal CT
      under general anesthesia for various diseases of the upper urinary tract. CT-GFR
      was measured with a single-slice dynamic acquisition and Patlak plot analysis. In
      five animals, the total CT-GFR appeared to be below normal, corresponding with
      mild (two animals) and moderate (two animals) increases of serum creatinine in
      four. In the two animals with normal or increased CT-GFR, serum creatinine was
      within the reference values. A significant negative logarithmic relationship was
      found between CT-GFR and serum creatinine values (P = 0.008; r2 = 0.75). No
      complications occurred during or following CT-GFR. CT examination provided
      clinically relevant information in 3/5 patients with possible ureteral
      obstruction and in 3/3 patients with suspected ureteral calculi. Single-slice
      dynamic CT-GFR was practical and provided clinically useful information in this
      small series of patients undergoing CT of the upper urinary tract. There was a
      significant relationship between CT-GFR and serum creatinine values, which
      supports the clinical potential of CT-GFR and justifies further investigation of
      this technique.

PMID- 20806875
TI  - Cardiac magnetic resonance imaging in normal dogs and two dogs with heart base
      tumor.
AB  - We describe the technique for in vivo cardiac-gated magnetic resonance imaging
      (MRI) in normal dogs and its application in two dogs with a large right atrial
      tumor. The dogs with a cardiac tumor were also imaged using contrast-enhanced
      magnetic resonance angiography (CE-MRA). Cardiac-gated MRI and CE-MRA are both
      feasible in animals with short acquisition times compatible with breath-hold
      imaging under anesthesia, and provide detailed two- and three-dimensional (3D)
      depiction of the cardiac anatomy and great vessels with or without contrast
      medium. Although cardiac MRI will not replace echocardiography, it is a powerful
      alternative technique to use when knowledge of the 3D anatomy of the vasculature
      is required, when precise volume measurements are needed or when myocardial
      characterization is indicated. As opposed to contrast-enhanced computed
      tomography angiography, cardiac MRI does not use ionizing radiation or iodinated
      contrast medium.

PMID- 20806876
TI  - Magnetic resonance imaging features of the temporomandibular joint in normal
      dogs.
AB  - Evaluation of the canine temporomandibular joint (TMJ) is important in the
      clinical diagnosis of animals presenting with dysphagia, malocclusion and jaw
      pain. In humans, magnetic resonance imaging (MRI) is the modality of choice for
      evaluation of the TMJ. The objectives of this study were to establish a technical
      protocol for performing MRI of the canine TMJ and describe the MRI anatomy and
      appearance of the normal canine TMJ. Ten dogs (one fresh cadaver and nine healthy
      live dogs) were imaged. MRIs were compared with cadaveric tissue sections. T1
      weighted (T1-W) transverse closed-mouth, T1-W sagittal closed-mouth, T1-W
      sagittal open-mouth, and T2-W sagittal open-mouth sequences were obtained. The
      condylar process of the mandible and the mandibular fossa of the temporal bone
      were hyperintense to muscle and isointense to hypointense to fat on T1-W images,
      mildly hyperintense to muscle on T2-W images, and were frequently heterogeneous.
      The articular disc was visible in 14/20 (70%) TMJs on T1-W images and 13/20 (65%)
      TMJs on T2-W images. The articular disc was isointense to hyperintense to muscle
      on T1-W images and varied from hypointense to hyperintense to muscle on T2-W
      images. The lateral collateral ligament was not identified in any joint. MRI
      allows evaluation of the osseous and certain soft tissue structures of the TMJ in
      dogs.

PMID- 20806877
TI  - Fluoroscopic study of the normal gastrointestinal motility and measurements in
      the Hispaniolan Amazon parrot (Amazona ventralis).
AB  - Contrast fluoroscopy is a valuable tool to examine avian gastrointestinal
      motility. However, the lack of a standardized examination protocol and reference
      ranges prevents the objective interpretation of motility disorders and other
      gastrointestinal abnormalities. Our goals were to evaluate gastrointestinal
      motility in 20 Hispaniolan Amazon parrots (Amazona ventralis) by contrast
      fluoroscopy. Each parrot was crop-fed an equal part mixture of barium sulfate and
      hand-feeding formula and placed in a cardboard box for fluoroscopy. Over a 3-h
      period, 1.5 minute segments of lateral and ventrodorsal fluoroscopy were recorded
      every 30 min. The gastric cycle and patterns of intestinal motility were
      described. The frequency of crop contractions, esophageal boluses, and gastric
      cycles were determined in lateral and ventrodorsal views. A range of 3.4-6.6
      gastric cycles/min was noted on the lateral view and 3.0-6.6 gastric cycles/min
      on the ventrodorsal view. Circular measurements of the proventriculus diameter,
      ventriculus width, and length were obtained using the midshaft femoral diameter
      as a standard reference unit. The upper limits of the reference ranges were 3.6
      and 4.7 femoral units for the proventriculus diameter in the lateral and
      ventrodorsal view, respectively. Two consecutive measurements were obtained and
      the measurement technique was found to have high reproducibility. In this study,
      we established a standardized protocol for contrast fluoroscopic examination of
      the gastrointestinal tract and a reliable measurement method of the
      proventriculus and ventriculus using femoral units in the Hispaniolan Amazon
      parrot.

PMID- 20806878
TI  - Ultrasonography of histologically normal parathyroid glands and thyroid lobules
      in normocalcemic dogs.
AB  - The purpose of this study is to characterize the sonographic appearance of canine
      parathyroid glands using high-resolution ultrasonography. Ten cadaver dogs were
      studied after euthanasia for reasons not relating to the parathyroid. The
      cervical region was examined using a 13-5 MHz linear transducer in right and left
      recumbency. Ultrasonographic features of the parathyroid and thyroid glands were
      compared with the gross and histopathologic findings. Thirty-five structures were
      identified sonographically as parathyroid glands but only 26 of 35 glands (74%
      positive predictive value) were proven to be normal parathyroid glands
      histopathologically. Of the nine false positives, five (14%) were proven to be
      lobular thyroid tissue. The remaining four (11%) structures were visible grossly
      or found histopathologically. There were no statistical differences between
      ultrasonographic and gross measurements of the parathyroid glands. The average
      size as seen sonographically was 3.3 x 2.2 x 1.7 mm and the average gross size
      was 3.7 x 2.6 x 1.6 mm (length, width, height). The average size of the thyroid
      lobules assessed sonographically was 2.3 x1.6 x 0.8 mm (length, width, height).
      Normal parathyroid glands can be identified using high-resolution
      ultrasonography. But some thyroid lobules will be misinterpreted as parathyroid
      glands; this will result in false positives when identifying parathyroid glands
      with ultrasonography.

PMID- 20806880
TI  - The sonographic appearance of intestinal mucosal fibrosis in cats.
AB  - The medical records of 11 cats with full-thickness intestinal biopsies and
      histopathologic confirmation of segmental mucosal fibrosis were reviewed. All
      cats received an abdominal ultrasonographic evaluation. The sonographic feature
      of a small intestinal mucosal hyperechoic band paralleling the submucosa was
      present in all cats. Other intestinal sonographic findings included wall
      thickening, and altered wall layering (increased mucosal echogenicity, thickened
      submucosa, and/or muscularis layer). None of the cats had complete loss of wall
      stratification. All cats had clinical signs related to the gastrointestinal (GI)
      tract at the time of presentation. Three of the 11 cats had palpably thickened
      small intestinal loops, 3/11 abdominal pain, and 2/11 abdominal fluid.
      Histopathologically, mucosal fibrosis was associated with inflammatory cell
      infiltrates in all cats. In those cats with histopathologic evidence of mural
      fibrosis, all cats had a visible hyperechoic band through several intestinal
      segments. We speculate that the hyperechoic mucosal band represents the zone of
      mucosal fibrosis. Independently and prospectively, we reviewed the clinical
      presentation of 35 cats having this visible hyperechoic mucosal band on
      ultrasound. Twenty-four of these 35 cats had clinical signs related to the
      digestive system at the time of record. Our study suggests that the hyperechoic
      mucosal band represents fibrosis, and in presence of concurrent GI signs, further
      diagnostic tests may be warranted.

PMID- 20806879
TI  - Ultrasonographic findings in Cairn Terriers with preclinical renal dysplasia.
AB  - Renal dysplasia is a hereditary disease characterized by abnormal differentiation
      of renal tissue. The ultrasonographic appearance of dysplastic canine kidneys has
      been reported in the late stage of the disease where inflammatory and
      degenerative changes are already present and the dogs are in chronic renal
      failure. In this study, we describe the ultrasonographic appearance of the
      kidneys of five related Cairn Terriers affected with renal dysplasia before the
      onset of clinical or laboratory evidence of renal failure. Common findings
      included poor corticomedullary definition and multifocal hyperechoic speckles in
      the renal medulla, or a diffusely hyperechoic medulla. Severity of
      ultrasonographic changes was related to the severity of histopathologic findings.
      The ability to detect dysplastic changes before clinical signs develop makes
      ultrasound a potentially useful screening method for canine renal dysplasia.

PMID- 20806881
TI  - Ultrasonographic features of grass awns in the urinary bladder.
AB  - Grass awns are a common cause of foreign body disease in animals, but little is
      known about their presence in the lower urinary tract. The ultrasonographic
      features of grass awns in vivo and in vitro have been described in detail. The
      purpose of this report is to describe the clinical and sonographic features of
      grass awns in the urinary bladder of dogs and cats. Three male Yorkshire terriers
      (one of which was examined twice) and one female domestic short-haired cat were
      evaluated for signs of lower urinary tract disease, and an intravesicular grass
      awn was suspected based on ultrasound examination. The grass awn appeared
      ultrasonographically as a bladder stone (n = 1) or a linear hyperechoic structure
      (n = 4) with or without acoustic shadowing that was easy to identify due to
      contrast with surrounding urine. The presence of a grass awn within the urinary
      bladder was confirmed during exploratory surgery. In all patients, the route of
      entry of the grass awn was thought to have been retrograde migration from the
      urethral opening. The ultrasonographic appearance of grass awns in the bladder is
      consistent with that in other tissues.

PMID- 20806882
TI  - Characterization of multiple acquired portosystemic shunts using transplenic
      portal scintigraphy.
AB  - We describe the scintigraphic patterns observed in 14 patients with confirmed
      multiple portosystemic shunts imaged via transplenic portal scintigraphy.
      Parameters evaluated included presence of multiple anomalous vessels, presence of
      hepatofugal flow caudal to spleen, and/or to cranial margin of the kidneys, slow
      absorption resulting in longer spleen to heart transit time, and presence of
      biphasic or fragmented bolus. Twenty-eight additional patients, 14 with a
      confirmed single portocaval and 14 with a portoazygos shunt, were used for
      comparison. Nine of 14 (64.3%) patients with multiple shunts had multiple
      vessels, five (35.7%) had a biphasic bolus, 13 (92.9%) had hepatofugal flow
      caudal to the cranial margin of the kidneys. In all single portocaval shunts, a
      single anomalous vessel was identified. None had hepatofugal flow caudal to the
      border of the kidneys. Among portoazygos shunts, 4/14 (28.6%) had flow caudal to
      the injection site. Six portoazygos and one portocaval shunts had biphasic bolus.
      Median transit time from spleen to heart was significantly longer (1.9 s) in
      patients with multiple shunts than in patients with a portocaval shunt (1.0 s),
      but not in patients with a portoazygos shunt (1.3 s). Although a distinct plexus
      of anomalous vessels is not detected in all patients with multiple shunts imaged
      using transplenic portal scintigraphy, findings of hepatofugal flow caudal to the
      margin of the kidneys, and longer transit time compared with single portocaval
      shunts were characteristic. Flow caudal to the splenic injection site but cranial
      to the kidneys and biphasic bolus can also be seen with a single congenital
      shunt.

PMID- 20806883
TI  - Comparison of interfractional variation in canine head position using palpation
      and a head-repositioning device.
AB  - Radiation treatment planning is performed on images that do not take variation in
      patient position into account. To compensate for expected variations in position
      of the patient, a three-dimensional expansion of the clinical target volume, or
      set-up margin, is added. Variations in patient position can be decreased through
      use of an immobilization device, allowing selection of a smaller set-up margin.
      The objective of this prospective study was comparison of interfractional
      variation in patient position between set-ups of the canine head region using
      palpation of bony landmarks and set-ups using a head-repositioning device.
      Fiducial markers were attached to the skull bones of three research dogs, and the
      dogs were positioned as for a typical radiation treatment of the head region
      using both set-up methods. A kilovoltage on-board imager was used to acquire
      orthogonal images and the difference between the x-, y-, and z-axis coordinates
      of each fiducial marker relative to the initial reference isocenter was measured.
      The difference in patient position for each axis coordinate was significantly
      lower for set-ups using the head-repositioning device than for set-ups using bony
      landmarks (P < 0.05). Ninety-five percent of the absolute values of the
      displacement vector differences were < 4.62 mm for set-up using bony landmarks,
      and < 1.93 mm for set-up using the head-repositioning device. A minimum set-up
      margin of 5-6 mm is recommended when patient set-up is based on bony landmarks
      and of 2-3 mm when the head-repositioning device is used.

PMID- 20806884
TI  - Comparison of 2,2'-bipyridine and 2,2'-bipyridyl-N,N'-dioxide as ligands in zinc
      complexes.
AB  - The complexation abilities of 2,2'-bipyridine (bipy) and 2,2'-bipyridyl-N,N'
      dioxide (bipydiox) toward zinc(II) and the influence of these ligands on the
      properties and reactivities of the investigated complexes are compared by means
      of mass spectrometry, IR multiphoton dissociation spectroscopy, and theoretical
      calculations. The binding energy of bipydiox to zinc is slightly smaller than
      that of bipy, namely, by 0.1 eV in the mixed complex [(bipy)(bipydiox)ZnCl](+).
      Accordingly, the differences in the properties and reactivities of the complexes
      of zinc(II)/bipydiox and zinc(II)/bipy are only minor. The mechanism of
      decarboxylation of [(L)Zn(CH(3)COO)](+) (L = bipy or bipydiox) is investigated in
      detail. The substantial difference between the ligands stems only from the
      possibility of oxygen transfer from bipydiox, which is here, however, observed
      only as a high-energy channel in the fragmentation of complexes
      [(bipydiox)Zn(CH(3)COO)](+).

PMID- 20806885
TI  - Integrated droplet analysis system with electrospray ionization-mass spectrometry
      using a hydrophilic tongue-based droplet extraction interface.
AB  - This paper describes a simple, robust, and integrated microchip-based system for
      droplet analysis with electrospray ionization-mass spectrometry (ESI-MS)
      detection. The microchip integrated multiple modules including a droplet
      generator, a droplet extraction interface, and a monolithic ESI emitter. The
      novel droplet extraction interface based on hydrophilic tongue structure was
      developed. The interface could transfer droplets from segmented phase to aqueous
      phase with high reliability and high controllability by coupling with a back
      pressure regulator. The flow injection mode was adopted to introduce the
      transferred droplets to the ESI emitter for minimizing the cross-contamination
      between droplets and achieving droplet matrix modification. The system
      performance was evaluated using angiotensin as a model sample, and high
      sensitivity (<1 MUM) and a good reproducibility of 5.2% RSD (n = 7) were
      obtained. The present device was further applied in the online monitoring of
      droplet-based microreaction for alkylation of peptide.

PMID- 20806886
TI  - DNA/ligand/ion-based ensemble for fluorescence turn on detection of cysteine and
      histidine with tunable dynamic range.
AB  - A new type of rapid, highly sensitive, and selective fluorescence turn-on assay
      for detection of cysteine and histidine using a DNA/ligand/ion ensemble is
      developed. This assay is based on the highly specific interaction between the
      amino acids and the metal ions and the strong fluorescence thiazole orange
      (TO)/DNA probe in a competition assay format. The resulting high sensitivity and
      selectivity for cysteine and histidine was achieved by changing the metal ions.
      The system is simple in design and fast in operation and is more convenient and
      promising than other methods. The novel strategy eliminated the need of organic
      cosolvents, enzymatic reactions, separation processes, chemical modifications,
      and sophisticated instrumentations. The detection and discrimination process can
      be seen with the naked eye under a hand-held UV lamp and can be easily adapted to
      automated high-throughput screening. The detection limit of this method is lower
      than or at least comparable to previous fluorescence-based methods. The dynamic
      range of the sensor can be tuned simply by adjusting the concentration of metal
      ions. Importantly, the protocol offers high selectivity for the determination of
      cysteine among amino acids found in proteins and in serum samples. The assay
      shows great potential for practical application as a disease-associated biomarker
      and will be needed to satisfy the great demand of amino acid determination in
      fields such as food processing, biochemistry, pharmaceuticals, and clinical
      analysis.

PMID- 20806888
TI  - Evaluating the fate of metals in air pollution control residues from coal-fired
      power plants.
AB  - Changes in emissions control at U.S. coal-fired power plants will shift metals
      content from the flue gas to the air pollution control (APC) residues. To
      determine the potential fate of metals that are captured through use of enhanced
      APC practices, the leaching behavior of 73 APC residues was characterized
      following the approach of the Leaching Environmental Assessment Framework.
      Materials were tested over pH conditions and liquid-solid ratios expected during
      management via land disposal or beneficial use. Leachate concentrations for most
      metals were highly variable over a range of coal rank, facility configurations,
      and APC residue types. Liquid-solid partitioning (equilibrium) as a function of
      pH showed significantly different leaching behavior for similar residue types and
      facility configurations. Within a facility, the leaching behavior of blended
      residues was shown to follow one of four characteristic patterns. Variability in
      metals leaching was greater than the variability in totals concentrations by
      several orders of magnitude, inferring that total content is not predictive of
      leaching behavior. The complex leaching behavior and lack of correlation to total
      contents indicates that release evaluation under likely field conditions is a
      better descriptor of environmental performance than totals content or linear
      partitioning approaches.

PMID- 20806887
TI  - Control of selectivity via nanochemistry: monolithic capillary column containing
      hydroxyapatite nanoparticles for separation of proteins and enrichment of
      phosphopeptides.
AB  - New monolithic capillary columns with embedded commercial hydroxyapatite
      nanoparticles have been developed and used for protein separation and selective
      enrichment of phosphopeptides. The rod-shaped hydroxyapatite nanoparticles were
      incorporated into the poly(2-hydroxyethyl methacrylate-co-ethylene
      dimethacrylate) monolith by simply admixing them in the polymerization mixture
      followed by in situ polymerization. The effect of percentages of monomers and
      hydroxyapatite nanoparticles in the polymerization mixture on the performance of
      the monolithic column was explored in detail. We found that the loading capacity
      of the monolith is on par with other hydroxyapatite separation media. However,
      the speed at which these columns can be used is higher due to the fast mass
      transport. The function of the monolithic columns was demonstrated with the
      separations of a model mixture of proteins including ovalbumin, myoglobin,
      lysozyme, and cytochrome c as well as a monoclonal antibody and its aggregates
      with protein A. Selective enrichment and MALDI/MS characterization of
      phosphopeptides fished-out from complex peptide mixtures of ovalbumin, alpha
      casein, and beta-casein digests were also achieved using the hydroxyapatite
      monolith.

PMID- 20806889
TI  - Comprehensive solid-state NMR characterization of electronic structure in
      ditechnetium heptoxide.
AB  - A relativistic density functional theory description of the electronic structure
      of Tc(2)O(7) has been evaluated by comparison with solid-state (99)Tc and (17)O
      NMR spectroscopic data (the former isotope is a weak beta emitter). Every site in
      the molecule can be populated by a nucleus with favorable NMR characteristics,
      providing the rare opportunity to obtain a comprehensive set of chemical shift
      and electric field gradient tensors for a small molecular transition-metal oxide.
      NMR parameters were computed for the central molecule of a (Tc(2)O(7))(17)
      cluster using standard ZORA-optimized all-electron QZ4P basis sets for the
      central molecule and DZ basis sets for the surrounding atoms. The magnitudes of
      the predicted tensor principal values appear to be uniformly larger than those
      observed experimentally, but the discrepancies were within the accuracy of the
      approximation methods used. The convergence of the calculated and measured NMR
      data suggests that the theoretical analysis has validity for the quantitative
      understanding of structural, magnetic, and chemical properties of Tc(VII) oxides
      in condensed phases.

PMID- 20806890
TI  - Larvicidal activity of Asarum heterotropoides root constituents against
      insecticide-susceptible and -resistant Culex pipiens pallens and Aedes aegypti
      and Ochlerotatus togoi.
AB  - We investigated the toxicity of (-)-asarinin, alpha-asarone, methyleugenol,
      pellitorine, and pentadecane identified in Asarum heterotropoides root to third
      instar larvae from insecticide-susceptible Culex pipiens pallens (KS-CP strain),
      Aedes aegypti, and Ochlerotatus togoi as well as field-collected C. p. pallens
      (DJ-CP colony), identified by polymerase chain reaction. Results were compared
      with those of two conventional mosquito larvicides: fenthion and temephos.
      Pellitorine (LC50, 2.08, 2.33, and 2.38 ppm) was 5.5, 10.8, and 25.6 times, 4.5,
      11.6, and 24.7 times, and 6.9, 11.1, and 24.6 times more toxic than (-)-asarinin,
      alpha-asarone, and methyleugenol against susceptible C. p. pallens, A. aegypti,
      and O. togoi larvae, respectively. Pentadecane was least toxic. Overall, all the
      compounds were less toxic than either fenthion or temephos. However, these
      compounds did not differ in toxicity against larvae from the two Culex strains,
      even though the DJ-CP larvae exhibited high levels of resistance to fenthion
      (resistance ratio (RR), 1179), chlorpyrifos (RR, 1174), fenitrothion (RR, 428),
      deltamethrin (RR, 316), chlorfenapyr (RR, 225), and alpha-cypermethrin (RR, 94).
      This finding indicates that the isolated compounds and the pyrethroid,
      organophosphorus, and pyrrole insecticides do not share a common mode of action
      or elicit cross-resistance. A. heterotropoides root-derived materials,
      particularly (-)-asarinin and pellitorine, merit further study as potential
      mosquito larvicides for the control of insecticide-resistant mosquito populations
      in light of global efforts to reduce the level of highly toxic synthetic
      insecticides in the aquatic environment.

PMID- 20806891
TI  - How the binding of substrates to a chiral polyborate counterion governs
      diastereoselection in an aziridination reaction: H-bonds in equipoise.
AB  - The stereochemistry-determining step of the self-assembled chiral Bronsted acid
      catalyzed aziridination reactions of MEDAM imines and three representative diazo
      nucleophiles has been studied using ONIOM(B3LYP/6-31G*:AM1) calculations. The
      origin of cis selectivity in the reactions of ethyldiazoacetate and trans
      selectivity in reactions of N-phenyldiazoacetamide can be understood on the basis
      of the difference in specific noncovalent interactions in the stereochemistry
      determining transition state. A H-bonding interaction between the amidic hydrogen
      and an oxygen atom of the chiral counterion has been identified as the key
      interaction responsible for this reversal in diastereoselectivity. This
      hypothesis was validated when a 3 degrees  diazoamide lacking this interaction
      showed pronounced cis selectivity both experimentally and calculationally.
      Similar trends in diastereoselection were observed in analogous reactions
      catalyzed by triflic acid. The broad implications of these findings and their
      relevance to chiral Bronsted acid catalysis are discussed.

PMID- 20806892
TI  - Controlled diastereo- and enantioselection in a catalytic asymmetric
      aziridination.
AB  - Chiral polyborate based Bronsted acids prepared from the VANOL and VAPOL ligands
      are known to catalyze the reaction of diarylmethyl imines with diazoesters to
      give cis-aziridines. In the present work, this same catalyst is shown to catalyze
      the reaction of the same imines with diazoacetamides to give trans-aziridines
      with the same high asymmetric inductions as seen with cis-aziridines, enabling
      the development of an unprecedented universal catalytic asymmetric aziridination
      protocol. The substrate scope is broad and includes imines prepared from both
      electron-rich and electron-poor aromatic aldehydes and also from 1 degrees , 2
      degrees , and 3 degrees  aliphatic aldehydes. The face selectivity of the
      addition to the imine was found to be independent of the diazo compounds. The (S)
      VANOL or (S)-VAPOL derived catalyst will cause both diazoesters and
      diazoacetamides to add to the Si-face of the imine when cis-aziridines are formed
      and both to add to the Re-face of the imine when trans-aziridines are formed.

PMID- 20806893
TI  - Mechanical tuning of molecular recognition to discriminate the single-methyl
      group difference between thymine and uracil.
AB  - Construction of enzyme-like artificial cavities is a complex and challenging
      subject. Rather than synthesizing complicated host molecules, we have proposed
      mechanical adaptation of relatively simple hosts within dynamic media to
      determine the optimum conformation for molecular recognition. Here we have
      applied this concept to one of the most challenging biomolecular recognition
      problems, i.e., that of discriminating thymine from uracil. We synthesized the
      novel cholesterol-armed triazacyclononane as a host molecule and subjected it to
      structural tuning by compression of its Langmuir monolayers in the absence and in
      the presence of Li(+) cations in the subphase. Experimental results confirm that
      the monolayer of triazacyclononane host selectively recognizes uracil over
      adenine (ca. 7 times based on the binding constant) and thymine (ca. 64 times)
      under optimized conditions ([LiCl] = 10 mM at surface pressure of 35 mN m(-1)).
      The concept of mechanical tuning of a host structure for optimization of
      molecular recognition offers a novel methodology in host-guest chemistry as an
      alternative to the more traditional molecular design strategies.

PMID- 20806894
TI  - Stacks of nucleic acids as molecular wires: direct measurement of the
      intermolecular band dispersion in multilayer guanine assemblies.
AB  - The intermolecular band dispersion related to the highest occupied molecular
      orbital in highly ordered, hydrated multilayer films of the DNA base guanine has
      been measured using photon-energy-dependent ultraviolet photoelectron
      spectroscopy. A bandwidth of 331 +/- 8 meV at room temperature and a small
      effective mass of about 1.11 times that of a free charge suggest a high intrinsic
      hole mobility along quasi-one-dimensional stacks formed perpendicular to layered,
      hydrogen-bound networks.

PMID- 20806895
TI  - Thermal behavior of soy protein fractions depending on their preparation methods,
      individual interactions, and storage conditions.
AB  - Different soy protein isolates (SPI) and whey soy protein (WSP) samples were
      obtained from fresh and stored soybean flour. Some samples were subjected to a
      long, cold storage. DSC thermograms of SPI showed the two characteristic
      endotherms, corresponding to denaturation of beta-conglycinin and glycinin. Low
      value of denaturation enthalpy and high glycinin denaturation temperature were
      related to a reduction of protein solubility of SPI. DSC thermograms of WSP also
      showed two characteristic endotherms, corresponding to Kunitz trypsin inhibitor
      and lectin. The methods and conditions of preparation and storage of WSP samples
      were factors that modified their thermal behavior. Some SPI-WSP mixtures (1:1)
      exhibited more complex thermograms and higher denaturation temperatures.
      Thermograms of SPI-denatured WSP mixtures showed that the thermal stabilization
      of soybean storage proteins was attributed to protein-protein interactions. The
      differences in the thermal behavior of single or mixed SPI and WSP could not be
      explained on the basis of mineral content.

PMID- 20806896
TI  - Effects of conformational restriction of 2-amino-3-benzoylthiophenes on A(1)
      adenosine receptor modulation.
AB  - 2-Amino-3-benzoylthiophenes (2A3BTs) have been widely reported to act as
      allosteric enhancers (AEs) at the A(1) adenosine receptor (A(1)AR). Herein we
      describe the synthesis of a series of 1-aminoindeno[1,2-c]thiophen-8-ones and a
      series of (2-aminoindeno[2,1-b]thiophen-3-yl)(phenyl)methanones as
      conformationally rigid analogues of the 2A3BTs. These compounds were screened
      using a functional assay of A(1)AR-mediated phosphorylation of extracellular
      signal-regulated kinases 1 and 2 (ERK1/2) in intact Chinese hamster ovary (CHO)
      cells to identify both potential agonistic effects as well as the ability to
      allosterically modulate the activity of the orthosteric agonist, N(6)-(R
      phenylisopropyl)adenosine (R-PIA). All of the 1-aminoindeno[1,2-c]thiophen-8-ones
      (14a-c and 17a-f) proved either to be inactive or behaved as antagonists in the
      functional assay. However, the (2-aminoindeno[2,1-b]thiophen-3
      yl)(phenyl)methanones with para-chloro substitution (compounds 25b, 25d, and 25f)
      did significantly augment the R-PIA response, indicating a positive allosteric
      effect.

PMID- 20806898
TI  - Electron-mediated CO oxidation on the TiO2(110) surface during electronic
      excitation.
AB  - The role of electrons and holes in the electronically excited oxidation of
      adsorbed CO on TiO(2)(110) has been investigated by tuning the surface electron
      and hole availability by the adsorption of Cl(2) or O(2). The presence of an
      electron acceptor (Cl(2) or O(2)) on the TiO(2)(110) surface causes upward band
      bending, increasing the excited hole availability and decreasing the excited
      electron availability in the near surface region. This enhances O(2) desorption
      and depresses CO(2) production during electronic excitation. This result gives
      clear evidence for the first time that the electronically excited CO oxidation
      reaction is caused by an electron-mediated process in contrast to O(2) desorption
      which is mediated by holes.

PMID- 20806897
TI  - Decomposition of vibrational shifts of nitriles into electrostatic and hydrogen
      bonding effects.
AB  - Infrared (IR) band shifts of isolated vibrational transitions can serve as
      quantitative and directional probes of local electrostatic fields, due to the
      vibrational Stark effect. However, departures from the Stark model can arise when
      the probe participates in specific, chemical interactions, such as direct
      hydrogen bonding. We present a method to identify and correct for these
      departures based on comparison of (13)C NMR chemical shifts and IR frequencies
      each calibrated in turn by a solvatochromic model. We demonstrate how the tandem
      use of these experimental observables can be applied to a thiocyanate-modified
      protein, ketosteroid isomerase, and show, by comparison to structural models,
      that changes in electrostatic field can be measured within the complex protein
      environment even in the background of direct hydrogen bonding to the probe.

PMID- 20806899
TI  - Fetuin-A and cystatin C are endogenous inhibitors of human meprin
      metalloproteases.
AB  - Meprin alpha and beta, zinc metalloproteinases, play significant roles in
      inflammation, including inflammatory bowel disease (IBD), possibly by activating
      cytokines, like interleukin 1beta, interleukin 18, or tumor growth factor alpha.
      Although a number of potential activators for meprins are known, no endogenous
      inhibitors have been identified. In this work, we analyzed the inhibitory
      potential of human plasma and identified bovine fetuin-A as an endogenous meprin
      inhibitor with a K(i) (inhibition constant) of 4.2 * 10(-5) M for meprin alpha
      and a K(i) of 1.1 * 10(-6) M meprin beta. This correlated with data obtained for
      a fetuin-A homologue from carp (nephrosin inhibitor) that revealed a potent
      meprin alpha and beta inhibition (residual activities of 27 and 22%,
      respectively) at a carp fetuin concentration of 1.5 * 10(-6) M. Human fetuin-A is
      a negative acute phase protein involved in inflammatory diseases, thus being a
      potential physiological regulator of meprin activity. We report kinetic studies
      of fetuin-A with the proteolytic enzymes astacin, LAST, LAST_MAM, trypsin, and
      chymotrypsin, indeed demonstrating that fetuin-A is a broad-range protease
      inhibitor. Fetuin-A inhibition of meprin alpha activity was 40 times weaker than
      that of meprin beta activity. Therefore, we tested cystatin C, a protein
      structurally closely related to fetuin-A. Indeed, cystatin C was an inhibitor for
      human meprin alpha (K(i) = 8.5 * 10(-6) M) but, interestingly, not for meprin
      beta. Thus, the identification of fetuin-A and cystatin C as endogenous
      proteolytic regulators of meprin activity broadens our understanding of the
      proteolytic network in plasma.

PMID- 20806900
TI  - Dietary modulation of gut functional ecology studied by fecal metabonomics.
AB  - A major source of intestinal metabolites results from both host and microbial
      processing of dietary nutrients. (1)H NMR-based metabolic profiling of mouse
      feces was carried out over time in different microbiome mouse models, including
      conventional (n = 9), conventionalized (n = 10), and "humanized" gnotobiotic mice
      inoculated with a model of human baby microbiota (HBM, n = 17). HBM mice were
      supplemented with Lactobacillus paracasei with (n = 10) and without (n = 7)
      prebiotics. Animals not supplemented with prebiotics received a diet enriched in
      glucose and lactose as placebo. In conventionalized animals, microbial
      populations and activities converged in term of multivariate mapping toward
      conventional mice. Both groups decreased bacterial processing of dietary proteins
      when switching to a diet enriched in glucose and lactose, as described with low
      levels of 5-aminovalerate, acetate, and propionate and high levels of lysine and
      arginine. The HBM model differs from conventional and conventionalized microbiota
      in terms of type, proportion, and metabolic activity of gut bacteria (lower short
      chain fatty acids (SCFAs), lactate, 5-aminovalerate, and oligosaccharides, higher
      bile acids and choline). The probiotics supplementation of HBM mice was
      associated with a specific amino acid pattern that can be linked to L. paracasei
      proteolytic activities. The combination of L. paracasei with the galactosyl
      oligosaccharide prebiotics was related to the enhanced growth of bifidobacteria
      and lactobacilli, and a specific metabolism of carbohydrates, proteins, and
      SCFAs. The present study describes how the assessment of metabolic changes in
      feces may provide information for studying nutrient-microbiota relationships in
      different microbiome mouse models.

PMID- 20806901
TI  - Isolation of potent and specific trypsin inhibitors from a DNA-encoded chemical
      library.
AB  - Collections of chemical compounds, individually attached to unique DNA fragments
      serving as amplifiable identification bar codes, are generally referred to as
      "DNA-encoded chemical libraries". Such libraries can be used for the de novo
      isolation of binding molecules against target proteins of interest. Here, we
      describe the synthesis and use of a DNA-encoded library based on benzamidine
      analogues, which allowed the isolation of a trypsin inhibitor with an IC(50)
      value of 3.0 nM, thus representing a >10 000-fold potency improvement compared to
      the parental compound. The novel trypsin inhibitor displayed an excellent
      selectivity toward other serine proteases. This study indicates that DNA-encoded
      libraries can be used for the facile "affinity maturation" of suboptimal binding
      compounds, thus facilitating drug development.

PMID- 20806903
TI  - Ambient pressure dry-gel conversion method for zeolite MFI synthesis using ionic
      liquid and microwave heating.
AB  - We report an ambient pressure synthesis method for silicate zeolite. This method
      combines the advantages of ionothermal synthesis, dry-gel conversion, and
      microwave radiation, making it a promising, safe, fast, and continuous process
      for industrial application.

PMID- 20806902
TI  - A new class of ligands for aqueous, lanthanide-catalyzed, enantioselective
      Mukaiyama aldol reactions.
AB  - The development of aqueous methods for generating enantiopure beta-hydroxy
      carbonyl compounds is an important goal because these subunits compose many
      bioactive compounds and the ability to synthesize these groups in water has
      environmental and cost benefits. In this communication, we report a new class of
      ligands for aqueous, lanthanide-catalyzed, asymmetric Mukaiyama aldol reactions
      for the synthesis of chiral beta-hydroxy ketones. Furthermore, we have used
      luminescence-decay measurements to unveil mechanistic information regarding the
      catalytic reaction via changes in water-coordination number. The precatalysts
      presented here yielded beta-hydroxy carbonyls from aliphatic and aryl substrates
      with outstanding syn:anti ratios and enantiometric excesses of up to 49:1 and
      97%, respectively.

PMID- 20806904
TI  - cis-2,2'-Bipyrimidine-bridged polynuclear complex: a stairway-like mixed-valent
      {Fe(4)} cluster.
AB  - We report the first example of a polynuclear discrete coordination compound
      exhibiting only bpym bridges and containing a first-row d transition metal. A
      smooth self-assembly one-pot synthetic route, starting from simply FeCl(2) and
      FeCl(3) hydrates, allowed us to prepare a tetranuclear Fe(4) cluster with a
      stairway-like structure and the formula cis-{[(H(2)O)Cl(3)Fe(III)
      MU(bpym)Fe(II)Cl(2)]}(2)-MU(bpym) (1) . All spectroscopic data suggest that
      complex 1 is a valence-localized mixed-valent Fe(II)-Fe(III) cluster with typical
      Mossbauer lines for both sites, which do not change with temperature. Reflectance
      spectroscopy did not allow one to distinguish an intervalence charge-transfer
      band. However, time-dependent density functional theory (DFT) calculations
      predict a weak high-energy Fe(II) -> Fe(III) transition. Regarding the magnetic
      properties, the high-spin Fe(II) and Fe(III) ions interact in a weakly
      antiferromagnetic way with isotropic J constants of only a few wavenumbers as
      derived from direct-current susceptibility and magnetization data. Broken
      symmetry DFT calculations support these observations.

PMID- 20806905
TI  - Biodegradability of lingering crude oil 19 years after the Exxon Valdez oil
      spill.
AB  - In 2001 and 2003, geospatial surveys of lingering oil were conducted in Prince
      William Sound (PWS) resulting in a prediction of significant acreage being
      contaminated with substantial subsurface oil from the 1989 Exxon Valdez oil spill
      (EVOS). In 2007, other researchers developed a mass weathering index (MWI) based
      on the degree of weathering of PAHs normalized to conserved biomarkers: if the
      degree of weathering of oil is 70% or more, further attempts at bioremediation
      would be unjustified. The objective of our study was to measure the
      biodegradability of the 19-year lingering oil in laboratory microcosms. Samples
      of beach substrate were collected from representative sites in PWS contaminated
      with oil residues of varying weathering states according to the MWI model. Enough
      sacrificial microcosms were set up to accommodate two treatments for each site
      (natural attenuation and biostimulation). Results indicated that lingering oil is
      biodegradable. Nutrient addition stimulated biodegradation compared to natural
      attenuation in all treatments regardless of the degree of weathering. The most
      weathered oil according to the MWI was the most biodegradable. Substantial
      biodegradation occurred in the natural attenuation microcosms due to the high
      sediment Total Kjeldahl Nitrogen (TKN), which served as a nitrogen source for
      biodegradation. Most of the observed biodegradation was due to the presence of
      dissolved oxygen. Nitrogen was a limiting factor but oxygen was the predominant
      one.

PMID- 20806907
TI  - Topsentinols, 24-isopropyl steroids from the marine sponge Topsentia sp.
AB  - Three isopropyl steroids, topsentinols K, L, and K trisulfate (1-3), were
      isolated from an undescribed species of Topsentia. The structures of the new
      compounds were determined by extensive 1D and 2D NMR experiments and mass
      spectrometry measurements. Topsentinol K trisulfate (3) inhibited the aspartic
      protease BACE1, although in a detergent-dependent manner suggestive of
      nonspecific aggregation.

PMID- 20806908
TI  - Caylobolide B, a macrolactone from symplostatin 1-producing marine cyanobacteria
      Phormidium spp. from Florida.
AB  - A Phormidium spp. collection from Key West, Florida, afforded caylobolide B (1),
      an analogue of the known macrolactone caylobolide A, previously isolated from a
      Lyngbya majuscula collection from the Bahamas. The planar structure of 1 was
      determined using NMR and MS experiments. The relative configuration for subunits
      C7-C9 and C25-C29 was assigned using Kishi's Universal NMR Database. Caylobolide
      B (1) displayed cytotoxic activity against HT29 colorectal adenocarcinoma and
      HeLa cervical carcinoma cells with IC(50) values of 4.5 and 12.2 MUM,
      respectively.

PMID- 20806909
TI  - Development of biodegradable foamlike materials based on casein and sodium
      montmorillonite clay.
AB  - Biodegradable foamlike materials based on a naturally occurring polymer (casein
      protein) and sodium montmorillonite clay (Na+ -MMT) were produced through a
      simple freeze-drying process. By utilizing DL-glyceraldehyde (GC) as a chemical
      cross-linking agent, the structural integrity of these new aerogels were
      remarkably improved when compared to those of the control system (without GC),
      with a minimal increase in the density from 0.11 to 0.12 g cm-3. The degree of
      perfection of the foamlike structures was another parameter that had a
      significant influence on the physical and thermal performances of the low density
      composites. The biodegradability of the aerogels was investigated in terms of the
      carbon dioxide (CO2) evolution for up to 8 weeks in compost media under
      controlled conditions.

PMID- 20806911
TI  - Selenium and sulfur in exchange reactions: a comparative study.
AB  - Cysteamine reduces selenocystamine to form hemiselenocystamine and then
      cystamine. The rate constants are k(1) = 1.3 * 10(5) M(-1) s(-1); k(-1) = 2.6 *
      10(7) M(-1) s(-1); k(2) = 11 M(-1) s(-1); and k(-2) = 1.4 * 10(3) M(-1) s(-1),
      respectively. Rate constants for reactions of cysteine/selenocystine are similar.
      Reaction rates of selenium as a nucleophile and as an electrophile are 2-3 and 4
      orders of magnitude higher, respectively, than those of sulfur. Sulfides and
      selenides are comparable as leaving groups.

PMID- 20806912
TI  - Diastereoselective synthesis of bulky, strongly nucleophilic, and
      configurationally stable P-stereogenic tricyclic phosphines.
AB  - A very simple, one-step highly diastereoselective synthesis of bulky,
      configurationally and air-stable P-chiral tricyclic phosphines 3, showing an
      exceptionally strong nucleophilic character, has been developed. This method
      involves the reaction of the stable phosphonium sila-ylide 1 with aryl- and alkyl
      substituted acetylene derivatives. Starting from commercially available chiral
      (R,S)-(+)-endo-2-norborneol, the corresponding enantiomerically pure phosphines
      were obtained with excellent enantioselectivities (ee >= 99%) and high chemical
      yields.

PMID- 20806913
TI  - Connecting energy landscapes with experimental rates for aminoacyl-tRNA
      accommodation in the ribosome.
AB  - Using explicit-solvent simulations of the 70S ribosome, the barrier-crossing
      attempt frequency was calculated for aminoacyl-tRNA elbow-accommodation. In seven
      individual trajectories (200-300 ns, each, for an aggregate time of 2.1 MUs), the
      relaxation time of tRNA structural fluctuations was determined to be ~10 ns, and
      the barrier-crossing attempt frequency of tRNA accommodation is ~1-10 MUs(-1).
      These calculations provide a quantitative relationship between the free-energy
      barrier and experimentally measured rates of accommodation, which demonstrate
      that the free-energy barrier of elbow-accommodation is less than 15 k(B)T, in
      vitro and in vivo.

PMID- 20806914
TI  - Enantioselective synthesis of (Z)-1,2-anti-2,5-anti-triol monosilyl ethers using
      a cross-metathesis allylboration sequence.
AB  - The enantioselective synthesis of (Z)-1,2-anti-2,5-anti-triol monosilyl ethers
      via a two-step sequence involving olefin cross-metathesis of beta
      alkoxyallylboronate 4 and subsequent allylboration of the derived bisboryl
      intermediate 6 provides triol monoethers 7 with good to excellent
      diastereoselectivity.

PMID- 20806915
TI  - Energy transfer from an individual quantum dot to a carbon nanotube.
AB  - Precision measurements of resonant energy transfer from isolated quantum dots
      (QDs) to individual carbon nanotubes (CNTs) exhibit unique features due to the
      one-dimensional nature of CNTs. In particular, excitons can be created at varying
      distances from the QD at different locations along the CNT length. This leads to
      large variations in energy transfer length scales for different QDs and a novel
      saturation of the energy transfer efficiency at ~96%, seemingly independent of
      CNT chirality.

PMID- 20806916
TI  - Resistive switches and memories from silicon oxide.
AB  - Because of its excellent dielectric properties, silicon oxide (SiO(x)) has long
      been used and considered as a passive, insulating component in the construction
      of electronic devices. In contrast, here we demonstrate resistive switches and
      memories that use SiO(x) as the sole active material and can be implemented in
      entirely metal-free embodiments. Through cross-sectional transmission electron
      microscopy, we determine that the switching takes place through the voltage
      driven formation and modification of silicon (Si) nanocrystals (NCs) embedded in
      the SiO(x) matrix, with SiO(x) itself also serving as the source of the formation
      of this Si pathway. The small sizes of the Si NCs (d ~ 5 nm) suggest that scaling
      to ultrasmall domains could be feasible. Meanwhile, the switch also shows robust
      nonvolatile properties, high ON/OFF ratios (>10(5)), fast switching (sub-100-ns),
      and good endurance (10(4) write-erase cycles). These properties in a SiO(x)-based
      material composition showcase its potentials in constructing memory or logic
      devices that are fully CMOS compatible.

PMID- 20806917
TI  - Scrutinizing the chemical nature and photophysics of an expanded
      hemiporphyrazine: the special case of [30]trithia
      2,3,5,10,12,13,15,20,22,23,25,30-dodecaazahexaphyrin.
AB  - Thirty pi-electron-expanded hemiporphyrazines 1a-c have been prepared by
      crossover condensation reaction of 2,5-diamino-1,3,4-thiadiazole and the
      corresponding phthalonitrile (3) or diiminoisoindoline (4) derivatives. The
      expanded azaporphyrin hexamers have been unequivocally characterized by means of
      spectroscopic, crystallographic, and electrochemical techniques. Weak
      intramolecular hydrogen bonding imposes a planar conformation to macrocycles.
      However, the overall electronic delocalization is low, and the nature of the
      resulting [30]heteroannulene is nonaromatic, as confirmed by NMR studies, XR
      diffraction analysis, and calculation of the NICS(0) value. Studies on a wide
      range of physicochemical features including ground, excited, reduced, and
      oxidized states provide evidence for the wide applicability of these 30 pi
      electron-expanded hemiporphyrazines in processes involving electron transfer. A
      key asset of our work is the systematic development of spectroscopic and kinetic
      markers for the formation and decay of all of the aforementioned species. Thirty
      pi-electron-expanded hemiporphyrazines evolve as broadly absorbing light
      harvesters with excited state energies of around 2.3 eV that are susceptible to
      facile one-electron reduction and one-electron oxidation reactions.

PMID- 20806918
TI  - Stereoselective cyclization of functionalized 1,n-diynes mediated by [X-Y]
      reagents [X-Y = R3Si-SnR'3 or (R2N)2B-SnR'3]: synthesis and properties of
      atropisomeric 1,3-dienes.
AB  - The borylstannane [-N(Me)CH(2)CH(2)(Me)N-]B-SnMe(3) is a superior reagent capable
      of effecting bisfunctionalization-cyclization in several highly functionalized
      1,n-diynes, 1,n-enynes, and 1,n-allenynes (including 1,2-dipropargylbenzenes,
      2,2'-dipropargylbiphenyls, 4,5-dipropargyldioxolanes, and 1,4-dipropargyl-beta
      lactams) where the more well-known silylstannanes fail. Variable-temperature NMR
      studies showed that conformational restraints imposed by selected backbones
      increase the activation barrier for the helical isomerization in (Z,Z)-dienes
      that are generated in the cyclization of the diynes. In the biphenyl and
      dioxolane systems, the reactions proceed with surprisingly good regio- and
      stereoselectivity. The resulting diazaborolidine derivatives are hydrolytically
      unstable but can be isolated by recrystallization or precipitation. For further
      synthetic applications, it is advantageous to convert these compounds in situ
      into the corresponding dioxaborolidines with either retention of the Me(3)Sn
      group or replacement of this group via halodestannylation. The configurations of
      the vinyl moieties are preserved in these reactions. Highly functionalized
      dibenzocyclooctadienes, which adorn the carbon frames of several important
      cytotoxic natural products, can be synthesized using this chemistry.

PMID- 20806919
TI  - Rhodium-catalyzed enantioselective 1,6-addition of arylboronic acids to
      enynamides: asymmetric synthesis of axially chiral allenylsilanes.
AB  - Rhodium-catalyzed asymmetric 1,6-addition of arylboronic acids to beta-alkynyl
      acrylamides substituted with a silyl group on the alkyne terminus took place to
      give high yields of axially chiral allenylsilanes with 94-99% enantioselectivity,
      which was realized by use of a rhodium/chiral diene complex.

PMID- 20806920
TI  - NMR-spectroscopic and solid-state investigations of cometal-free asymmetric
      conjugate addition: a dinuclear paracyclophaneimine zinc methyl complex.
AB  - We present herein the first indications for dimeric structures in cometal-free
      asymmetric conjugate addition reactions of dialkylzinc reagents with aldehydes.
      These are revealed by nonlinear effect (NLE) studies. A monomer-dimer equilibrium
      can be assumed which explains the increase of the ee value in the product over
      time. Also, DOSY NMR spectroscopic measurements indicate the existence of the
      catalyst as [LZnEt](n) complexes in solution. Additionally, the first X-ray
      structure of a zinc complex with a [2.2]paracyclophane ligand was determined. The
      structures of the zinc complexes are supported by DFT calculations of monomeric
      and dimeric species.

PMID- 20806921
TI  - Manganese porphyrins catalyze selective C-H bond halogenations.
AB  - We report a manganese porphyrin mediated aliphatic C-H bond chlorination using
      sodium hypochlorite as the chlorine source. In the presence of catalytic amounts
      of phase transfer catalyst and manganese porphyrin Mn(TPP)Cl 1, reaction of
      sodium hypochlorite with different unactivated alkanes afforded alkyl chlorides
      as the major products with only trace amounts of oxygenation products. Substrates
      with strong C-H bonds, such as neopentane (BDE =~100 kcal/mol) can be also
      chlorinated with moderate yield. Chlorination of a diagnostic substrate,
      norcarane, afforded rearranged products indicating a long-lived carbon radical
      intermediate. Moreover, regioselective chlorination was achieved by using a
      hindered catalyst, Mn(TMP)Cl, 2. Chlorination of trans-decalin with 2 provided
      95% selectivity for methylene-chlorinated products as well as a preference for
      the C2 position. This novel chlorination system was also applied to complex
      substrates. With 5alpha-cholestane as the substrate, we observed chlorination
      only at the C2 and C3 positions in a net 55% yield, corresponding to the least
      sterically hindered methylene positions in the A-ring. Similarly, chlorination of
      sclareolide afforded the equatorial C2 chloride in a 42% isolated yield.
      Regarding the mechanism, reaction of sodium hypochlorite with the Mn(III)
      porphyrin is expected to afford a reactive Mn(V)?O complex that abstracts a
      hydrogen atom from the substrate, resulting in a free alkyl radical and a Mn(IV)
      OH complex. We suggest that this carbon radical then reacts with a Mn(IV)-OCl
      species, providing the alkyl chloride and regenerating the reactive Mn(V)?O
      complex. The regioselectivity and the preference for CH(2) groups can be
      attributed to nonbonded interactions between the alkyl groups on the substrates
      and the aryl groups of the manganese porphyrin. The results are indicative of a
      bent [Mn(v)?O---H---C] geometry due to the C-H approach to the Mn(v)?O (dpi-ppi)*
      frontier orbital.

PMID- 20806922
TI  - Enzymatic ring-opening mechanism of verdoheme by the heme oxygenase: a combined X
      ray crystallography and QM/MM study.
AB  - The least understood mechanism during heme degradation by the enzyme heme
      oxygenase (HO) is the third step of ring opening of verdoheme to biliverdin, a
      process which maintains iron homeostasis. In response to this mechanistic
      uncertainty, we launched a combined study of X-ray crystallography and
      theoretical QM/MM calculations, designed to elucidate the mechanism. The air
      sensitive ferrous verdoheme complex of HmuO, a heme oxygenase from
      Corynebacterium diphtheriae, was crystallized under anaerobic conditions.
      Spectral analysis of the azide-bound verdoheme-HmuO complex crystals assures that
      the verdoheme group remains intact during the crystallization and X-ray
      diffraction measurement. The structure offers the first solid evidence for the
      presence of a water cluster in the distal pocket of this catalytically critical
      intermediate. The subsequent QM/MM calculations based on this crystal structure
      explore the reaction mechanisms starting from the FeOOH-verdoheme and FeHOOH
      verdoheme complexes, which mimic, respectively, the O(2)- and H(2)O(2)-supported
      degradations. In both mechanisms, the rate-determining step is the initial O-O
      bond breaking step, which is either homolytic (for FeHOOH-verdoheme) or coupled
      to electron and proton transfers (in FeOOH-verdoheme). Additionally, the
      calculations indicate that the FeHOOH-verdoheme complex is more reactive than the
      FeOOH-verdoheme complex in accord with experimental findings. QM energies with
      embedded MM charges are close to and yield the same conclusions as full QM/MM
      energies. Finally, the calculations highlight the dominant influence of the
      distal water cluster which acts as a biocatalyst for the conversion of verdoheme
      to biliverdin in the two processes, by fixing the departing OH and directing it
      to the requisite site of attack, and by acting as a proton shuttle and a haven
      for the highly reactive OH(-) nucleophile.

PMID- 20806923
TI  - Phase separation and suppression of the structural and magnetic transitions in
      superconducting doped iron tellurides, Fe(1+x)Te(1-y)S(y).
AB  - Single crystal and powder samples of the series of iron chalcogenide
      superconductors with nominal composition, Fe((1.15))Te((1-)y)S(y), are found to
      form for 0 <= y <= 0.15. They crystallize in the tetragonal anti-PbO structure,
      which is composed of layers of edge-shared Fe(Te, S)(4) tetrahedra. For y = 0,
      Fe(1+x)Te (x ~ 0.12(1)) is nonsuperconducting and undergoes a tetragonal (P4/nmm)
      to monoclinic (P2(1)/m) structural transition at ~65 K, associated with the onset
      of commensurate antiferromagnetic order at q = (0.5 0 0.5). We show that on
      sulfur substitution, Fe(1+x)Te(1-y)S(y) becomes orthorhombic (Pmmn) at low
      temperature for 0 <= y <= 0.015, where the greatly suppressed magnetic scattering
      is now incommensurate at q = (0.5-delta 0 0.5) and possesses short ranged
      magnetic correlations that are well fitted with a two-dimensional Warren peak
      shape. At much higher concentrations of S (y >= 0.075), there is suppression of
      both the structural and magnetic transitions and a superconducting transition at
      9 K is observed. Between these two composition regimes, there exists a region of
      phase separation (0.025 <= y <= 0.05), where the low temperature neutron
      diffraction data is best refined with a model containing both the tetragonal and
      orthorhombic phases. The increase in the amount of sulfur is found to be
      associated with a reduction in interstitial iron, x. Microprobe analysis of a
      single crystal of composition Fe((1.123(5)))Te((0.948(4)))S((0.052(4))) confirms
      the presence of compositional variation within the crystals, rationalizing the
      observed phase separation.

PMID- 20806924
TI  - Spatial control of cell adhesion and patterning through mussel-inspired surface
      modification by polydopamine.
AB  - The spatial control and patterning of mammalian cells were achieved by using the
      universal adhesive property of mussel-inspired polydopamine (PDA). The self
      polymerization of dopamine, a small molecule inspired by the DOPA motif of mussel
      foot proteins, resulted in the formation of a PDA adlayer when aqueous dopamine
      solution was continuously injected into poly(dimethylsiloxane) microchannels. We
      found that various cells (fibrosarcoma HT1080, mouse preosteoblast MC3T3-E1, and
      mouse fibroblast NIH-3T3) predominantly adhered to PDA-modified regions,
      maintaining their normal morphologies. The cells aligned in the direction of
      striped PDA patterns, and this tendency was not limited by the type of cell line.
      Because PDA modification does not require complex chemical reactions and is
      applicable to any type of material, it enables cell patterning in a simple and
      versatile manner as opposed to conventional methods based on the immobilization
      of adhesive proteins. The PDA-based method of cell patterning should be useful in
      many biomaterial research areas such as the fabrication of tissue engineering
      scaffolds, cell-based devices for drug screening, and the fundamental study of
      cell-material interactions.

PMID- 20806925
TI  - Magnetic hydrogels derived from polysaccharides with improved specific power
      absorption: potential devices for remotely triggered drug delivery.
AB  - We report on novel ferrogels derived from polysaccharides (sodium alginate and
      chitosan) with embedded iron oxide nanoparticles synthesized in situ and their
      combination with thermally responsive poly(N-isopropylacrylamide) for externally
      driven drug release using AC magnetic fields. Samples were characterized by Raman
      spectroscopy, transmission electron microscopy, and magnetic measurements. The
      obtained nanoparticles were found to be of ~10 nm average size, showing magnetic
      properties very close to those of the bulk material. The thermal response was
      measured by power absorption experiments, finding specific power absorption
      values between 100 and 300 W/g, which was enough for attaining the lower critical
      solution temperature of the polymeric matrix within few minutes. This fast
      response makes these materials good candidates for externally controlled drug
      release.

PMID- 20806926
TI  - [2 + 2] Photochemical cycloaddition/ring opening of 6-alkenyl-2,3-dihydro-4
      pyridones.
AB  - During the course of a study aimed at constructing azaspirocycles from 2,3
      dihydro-4-pyridones, an unexpected product was obtained in the SET ring-opening
      reaction of photocycloadduct 1. Differences in reactivity between homologues 1
      and 2 were observed in the presence of SmI(2). Tricyclic ketone 2 afforded
      azaspiro[5.5]undecane 15 when treated with SmI(2); however, when ketone 1 was
      submitted to similar reaction conditions a double ring-opening/reduction sequence
      gave cis-piperidinol 10.

PMID- 20806927
TI  - Dynamics of molecular adsorption and rotation on nonequilibrium sites.
AB  - It is generally accepted that important events on surfaces such as diffusion and
      reactions can be adsorption site dependent. However, due to their short lifetime
      and low concentration in most systems, adsorbates on nonequilibrium adsorption
      sites remain largely understudied. Using low-temperature scanning tunneling
      microscopy, site-dependent adsorption is shown for the molecule butyl methyl
      sulfide, which is trapped in multiple metastable adsorption sites upon deposition
      onto a Au(111) surface at 5 K. As this molecule does not have enough energy to
      diffuse to its preferred adsorption site on the surface, it is possible to study
      the behavior of individual molecules in a variety of nonequilibrium sites. Here
      we present atomic-scale data of the same chemical species in three independent,
      metastable adsorption sites and equilibration to a single equilibrium site as a
      function of either electrical or thermal excitation. Butyl methyl sulfide
      exhibits distinctly different physical properties at all four adsorption sites,
      including rotational dynamics and appearance in scanning tunneling microscopy
      (STM) images. An energy profile is proposed for the adsorption and equilibration
      of these species, and a correlation is drawn between rotational barrier and
      adsorption energy.

PMID- 20806928
TI  - Chlorinated iridoid glucosides from Veronica longifolia and their antioxidant
      activity.
AB  - From Veronica longifolia were isolated three chlorinated iridoid glucosides,
      namely, asystasioside E (6) and its 6-O-esters 6a and 6b, named longifoliosides A
      and B, respectively. The structures of 6a and 6b were proved by analysis of their
      spectroscopic data and by conversion to the catalpol ester verproside (5a) or to
      catalpol (5), respectively. The configuration of the previously known vanilloyl
      analogue, urphoside B, was shown to be the 6beta-epimer (6c) of the structure
      originally reported. Longifoliosides A (6a) and B (6b) were found to exhibit
      radical-scavenging activity against nitric oxide, superoxide, and 2,2-diphenyl-1
      picrylhydrazyl radicals.

PMID- 20806929
TI  - BH4- self-diffusion in liquid LiBH4.
AB  - The hydrogen dynamics in solid and in liquid LiBH4 was studied by means of
      incoherent quasielastic neutron scattering. Rotational jump diffusion of the BH4-
      subunits on the picosecond scale was observed in solid LiBH4. The characteristic
      time constant is significantly shortened when the system transforms from the low
      temperature phase to the high-temperature phase at 383 K. In the molten phase of
      LiBH4 above 553 K, translational diffusion of the BH4- units is found. The
      measured diffusion coefficients are in the 10(-5)cm2/s range at temperatures
      around 700 K, which is in the same order of magnitude as the self-diffusion of
      liquid lithium or the diffusion of ions in molten alkali halides. The temperature
      dependence of the diffusion coefficient shows an Arrhenius behavior, with an
      activation energy of Ea = 88 meV and a prefactor of D0 = 3.1 * 10(-4)cm2/s.

PMID- 20806930
TI  - Renner-teller effect, spin-orbit coupling, and fermi resonance in BrCN(+)
      (X(2)Pi): a combined experimental and theoretical study.
AB  - The spin-vibronic energy levels of BrCN(+) (X(2)Pi) up to 7700 cm(-1) above the
      vibrational ground state have been measured using zero-kinetic energy
      photoelectron spectroscopy (ZEKE) and tunable coherent extreme ultraviolet (XUV)
      light. The fundamental bands for C=N stretching, Br-C=N bending, and C-Br
      stretching vibrations have been measured, and a strong bending excitation was
      observed. The Renner-Teller effect and the Fermi interaction between the C-Br
      stretching and the Br-C=N bending have been observed experimentally. To
      characterize the spin-vibronic interaction in BrCN(+) (X(2)Pi), an effective
      diabatic model Hamiltonian with spectroscopic parameters describing these
      interactions was used to calculate the vibronic energy levels. The spectroscopic
      parameters have been determined by fitting the experimental data. Theoretical
      calculations based on the diabatic model were also performed. The theoretical
      spectroscopic parameters have been calculated using the potential energy surfaces
      reported by Biczysko and Tarroni (Chem. Phys. Lett. 2005, 415, 223). The
      calculated vibronic energy levels and spectroscopic parameters have been compared
      with those from the experimental data. For the diabatic potential energy matrix,
      the ab initio calculations provide good description of the diagonal elements,
      however, the off-diagonal elements deviate appreciably from those determined by
      experimental data. By analyzing the ZEKE spectrum of the ground vibrational band,
      the first adiabatic ionization energy for BrCN has been determined as 95 675.5 +/
      2.0 cm(-1).

PMID- 20806931
TI  - Regulation of human carbonyl reductase 3 (CBR3; SDR21C2) expression by Nrf2 in
      cultured cancer cells.
AB  - Carbonyl reduction is a central metabolic process that controls the level of key
      regulatory molecules as well as xenobiotics. Carbonyl reductase 3 (CBR3;
      SDR21C2), a member of the short-chain dehydrogenase/reductase (SDR) superfamily,
      has been poorly characterized so far, and the regulation of its expression is a
      complete mystery. Here, we show that CBR3 expression is regulated via Nrf2, a key
      regulator in response to oxidative stress. In human cancer cell lines, CBR3 mRNA
      was expressed differentially, ranging from very high (A549, lung) to very low (HT
      29, colon; HepG2, liver) levels. CBR3 protein was highly expressed in SW-480
      (colon) cells but was absent in HCT116 (colon) and HepG2 cells. CBR3 mRNA could
      be induced in HT-29 cells by Nrf2 agonists [sulforaphane (SUL, 7-fold) and
      diethyl maleate (DEM, 4-fold)] or hormone receptor ligand Z-guggulsterone (5
      fold). Aryl hydrocarbon receptor agonist B[k]F failed to induce CBR3 mRNA after
      incubation for 8 h but elevated CBR3 levels after 24 h, most likely mediated by
      B[k]F metabolites that can activate Nrf2 signaling. Inhibition of Nrf2-activating
      upstream kinase MEK/ERK by PD98059 weakened DEM-mediated induction of CBR3 mRNA.
      Proteasome inhibitors MG-132 (5 MUM) and bortezomib (50 nM) dramatically
      increased the level of CBR3 mRNA, obviously because of the increase in the level
      of Nrf2 protein. While siRNA-mediated knockdown of Nrf2 led to a decrease in the
      level of CBR3 mRNA in A549 cells (30% of control), Keap1 knockdown increased the
      level of CBR3 mRNA expression in HepG2 (9.3-fold) and HT-29 (2.7-fold) cells.
      Here, we provide for the first time evidence that human CBR3 is a new member of
      the Nrf2 gene battery.

PMID- 20806932
TI  - Abnormally high ammonium of natural origin in a coastal aquifer-aquitard system
      in the Pearl River Delta, China.
AB  - High-nitrogen loadings of rivers and aquifers systems are a major concern because
      of potential effects on human health and water quality impacts such as
      eutrophication of lakes and coastal zones. This nitrogen enrichment is commonly
      attributed to anthropogenic sources such as sewage and agricultural and
      industrial wastes. The aims of this study were to delineate spatial distribution
      of groundwater ammonium in the coastal aquifer system in Pearl River Delta (PRD),
      China and to identify the origin of the abnormally high ammonium. A total of 40
      boreholes were drilled to collect core samples of the aquitard and groundwater
      samples in the basal aquifer. The core samples were used for extraction of pore
      water for centrifugation and bulk chemical analyses in laboratory. Unlike
      previous studies which focused mainly on the aquifer, this study treated the
      aquifer-aquitard system as a hydrogeochemical continuum. The results show that
      the aquifer-aquitard system contains an exceptionally large total ammonium mass.
      Ammonium occurred at concentrations up to 390 mg/L in the basal sand Pleistocene
      aquifer 20-50 m deep, the largest concentration reported for groundwater
      globally. This ammonium was natural, areally extensive (1600 km(2)) and
      originated in the overlying Holocene-Pleistocene aquitard and entered the aquifer
      by groundwater transport and diffusion. Total ammonium in the aquifer (190 *
      10(6) kg) was exceeded by total ammonium in the aquitard (8600 * 10(6) kg) by a
      factor of 45. Much organic nitrogen remained in the aquitard available for
      conversion to ammonium. This natural ammonium in the aquifer was slowly
      transported into the PRD river channels and the estuary of the South China Sea.
      The rate of this contribution will likely be greatly increased by sand dredging
      in the river channels and estuary. Although the ammonium in PRD groundwater
      occurred in the largest concentrations and mass reported globally, the literature
      shows no reports of other delta aquitards having been examined for ammonium
      occurrence and therefore abundant ammonium formed in aquitards rich in organic
      matter may not be uncommon and this "geologic" source of ammonium may present a
      large and hitherto unappreciated source of nitrogen discharging to surface
      waters.

PMID- 20806933
TI  - Comparative assessment of life cycle assessment methods used for personal
      computers.
AB  - This article begins with a summary of findings from commonly cited life cycle
      assessments (LCA) of Information and Communication Technology (ICT) products.
      While differing conclusions regarding environmental impact are expected across
      product segments (mobile phones, personal computers, servers, etc.) significant
      variation and conflicting conclusions are observed even within product segments
      such as the desktop Personal Computer (PC). This lack of consistent conclusions
      and accurate data limits the effectiveness of LCA to influence policy and product
      design decisions. From 1997 to 2010, the majority of published studies focused on
      the PC concluded that the use phase contributes most to the life cycle energy
      demand of PC products with a handful of studies suggesting that manufacturing
      phase of the PC has the largest impact. The purpose of this article is to
      critically review these studies in order to analyze sources of uncertainty,
      including factors that extend beyond data quality to the models and assumptions
      used. These findings suggest existing methods to combine process-based LCA data
      with product price data and remaining value adjustments are not reliable in
      conducting life cycle assessments for PC products. Recommendations are provided
      to assist future LCA work.

PMID- 20806934
TI  - Optical and electrical measurement of energy transfer between nanocrystalline
      quantum dots and photosystem I.
AB  - In the natural photosynthesis process, light harvesting complexes (LHCs) absorb
      light and pass excitation energy to photosystem I (PSI) and photosystem II
      (PSII). In this study, we have used nanocrystalline quantum dots (NQDs) as an
      artificial LHC by integrating them with PSI to extend their spectral range. We
      have performed photoluminescence (PL) and ultrafast time-resolved absorption
      measurements to investigate this process. Our PL experiments showed that emission
      from the NQDs is quenched, and the fluorescence from PSI is enhanced. Transient
      absorption and bleaching results can be explained by fluorescence resonance
      energy transfer (FRET) from the NQDs to the PSI. This nonradiative energy
      transfer occurs in ~6 ps. Current-voltage (I-V) measurements on the composite NQD
      PSI samples demonstrate a clear photoresponse.

PMID- 20806935
TI  - Fast and simple droplet sampling of sap from plant tissues and capillary
      microextraction of soluble saccharides for picogram-scale quantitative
      determination with GC-MS.
AB  - Soluble saccharides are very important metabolites of the life cycle and
      synthesis of structural polysaccharide components (cellulose, hemicellulose,
      pectin, etc.) of cell walls. A new method for droplet sampling of saps from
      tissues of organisms and manipulation routines in capillaries for extraction,
      derivation, and partitioning were developed for picogram-scale quantitative
      determination with gas chromatography-mass spectrometry (GC-MS). Five to ten
      microliters of sap was sampled with a glass capillary containing ribitol
      (internal standard). Subsequently, the analytes were acetylated with acetic
      anhydride and catalyzed by 1-methylimidazole. Finally, the soluble saccharides
      were qualitatively detected with GC-MS SIM (selective ion monitoring) mode. The
      linear ranges of the method were up to 1*10(-6) mol/L and the theoretically
      lowest limits of detection (LOD, s/n>=3) were up to 1*10(-9) mol/L. The method is
      suitable and applicable to analysis of soluble monosaccharides in fresh tissues
      and other aqueous samples in wide fields of agriculture, food science, biological
      sciences, and even medical studies.

PMID- 20806937
TI  - Analysis of kinetic Langmuir model. Part I: Integrated kinetic Langmuir equation
      (IKL): a new complete analytical solution of the Langmuir rate equation.
AB  - In the article, a new integrated kinetic Langmuir equation (IKL) is derived. The
      IKL equation is a simple and easy to analyze but complete analytical solution of
      the kinetic Langmuir model. The IKL is compared with the nth-order, mixed 1,2
      order, and multiexponential kinetic equations. The impact of both equilibrium
      coverage theta(eq) and relative equilibrium uptake u(eq) on kinetics is
      explained. A newly introduced Langmuir batch equilibrium factor f(eq) that is the
      product of both parameters theta(eq)u(eq) is used to determine the general
      kinetic behavior. The analysis of the IKL equation allows us to understand fully
      the Langmuir kinetics and explains its relation with respect to the empirical
      pseudo-first-order (PFO, i.e., Lagergren), pseudo-second-order (PSO), and mixed
      1,2-order kinetic equations, and it shows the conditions of their possible
      application based on the Langmuir model. The dependence of the initial adsorption
      rate on the system properties is analyzed and compared to the earlier published
      approximate equations.

PMID- 20806936
TI  - Phytochemicals from Acacia confusa heartwood extracts reduce serum uric acid
      levels in oxonate-induced mice: their potential use as xanthine oxidase
      inhibitors.
AB  - In this study, the antihyperuricemic effect of Acacia confusa heartwood extracts
      and their phytochemicals on potassium oxonate (PO)-induced acute hyperuricemia
      was investigated for the first time. All treatments at the same dosage (100
      mmol/kg) were administered to the abdominal cavity of PO-induced hyperuricemic
      mice, and serum uric acid level was measured at 3 h after administration. In
      experimental mice, serum uric acid level was significantly suppressed by the
      administration of A. confusa heartwood extracts and their major phytochemicals, (
      )-2,3-cis-3,4-cis-3,3',4,4',7,8-hexahydroxyflavan, (-)-2,3-cis-3,4-cis-4'-methoxy
      3,3',4,7,8-pentahydroxyflavan, melanoxetin, transilitin, and okanin, relative to
      the PO group. The direct inhibitory effect of these five compounds on xanthine
      oxidase (XOD) activity was examined using isothermal titration calorimetry (ITC).
      Among them, melanoxetin showed a more remarkable inhibitory effect on XOD
      activity than allopurinol, a clinical drug used for XOD inhibitor. To further
      understand the stereochemistry between XOD and melanoxetin (or allopurinol),
      structure-based molecular modeling was performed. Melanoxetin undergoes extended
      interactions in the hydrophobic region via the 3',4'-dihydroxyphenyl moiety, thus
      accounting for its higher binding affinity to XOD than allopurinol. These results
      indicate that A. confusa heartwood extracts and their major phytochemicals
      exhibit strong XOD inhibitory effects, which reduce serum uric acid levels while
      inhibiting uric acid generation in purine metabolism.

PMID- 20806938
TI  - Protein oxidation enhances hydration but suppresses water-holding capacity in
      porcine longissimus muscle.
AB  - Pork longissimus muscle was oxidized at 4  degrees C by mixed 10 MUM FeCl(3)/100
      MUM ascorbate with 1, 5, 10, 20, 30, 40, or 50 mM H(2)O(2) (pH 6.2). Oxidation
      with >1 mM H(2)O(2) for 40 min significantly (P < 0.05) enhanced hydration of
      muscle samples, whereas oxidation with 40 and 50 mM H(2)O(2) for 2 min or with 20
      mM H(2)O(2) for 40 min caused pronounced declines in water-holding capacity and
      product yield. The changes coincided with marked increases in the protein
      carbonyl content, TBARS formation, and cross-linking of both myofibrillar and
      sarcoplasmic proteins. Dye-tracing tests showed that the enhanced hydration at >1
      mM H(2)O(2) was due to facilitated water diffusion into muscle tissue. This
      result was strongly corroborated by microscopic images that illustrated
      enlargements of intercellular spacing, that is, gaps, in oxidized muscle tissue,
      which served as canals for water diffusion.

PMID- 20806939
TI  - Analogues of morphanthridine and the tear gas dibenz[b,f][1,4]oxazepine (CR) as
      extremely potent activators of the human transient receptor potential ankyrin 1
      (TRPA1) channel.
AB  - The TRPA1 channel can be considered as a key biological sensor to irritant
      chemicals. In this paper, the discovery of 11H-dibenz[b,e]azepines
      (morphanthridines) and dibenz[b,f][1,4]oxazepines is described as extremely
      potent agonists of the TRPA1 receptor. This has led to the discovery that most of
      the known tear gases are potent TRPA1 activators. The synthesis and biological
      activity of a number of substituted morphanthridines and
      dibenz[b,f][1,4]oxazepines have given insight into the SAR around this class of
      TRPA1 agonists, with EC(50) values ranging from 1 MUM to 0.1 nM. Compounds 6 and
      32 can be considered as the most potent TRPA1 agonists known to date, with 6 now
      being used successfully as a screening tool in the discovery of TRPA1
      antagonists. The use of ligands such as 6 and 32 as pharmacological tools may
      contribute to the basic knowledge of the TRPA1 channel and advance the
      development of TRPA1 antagonists as potential treatment for conditions involving
      TRPA1 activation, including asthma and pain.

PMID- 20806941
TI  - Medicinal chemistry of siRNA delivery.

PMID- 20806940
TI  - Crystal structures of HLA-A*0201 complexed with Melan-A/MART-1(26(27L)-35)
      peptidomimetics reveal conformational heterogeneity and highlight degeneracy of T
      cell recognition.
AB  - There is growing interest in using tumor associated antigens presented by class I
      major histocompatibility complex (MHC-I) proteins as cancer vaccines. As native
      peptides are poorly stable in biological fluids, researchers have sought to
      engineer synthetic peptidomimetics with greater biostability. Here, we
      demonstrate that antigenic peptidomimetics of the Melan-A/MART-1(26(27L)-35)
      melanoma antigen adopt strikingly different conformations when bound to MHC-I,
      highlighting the degeneracy of T cell recognition and revealing the challenges
      associated with mimicking native peptide conformation.

PMID- 20806942
TI  - Microcalorimetric and SAXS determination of PEO-SDS interactions: the effect of
      cosolutes formed by ions.
AB  - The effect of different ionic cosolutes (NaCl, Na(2)SO(4), Li(2)SO(4), NaSCN,
      Na(2)[Fe(CN)(5)NO], and Na(3)[Co(NO)(6)]) on the interaction between sodium
      dodecyl sulfate (SDS) and poly(ethylene oxide) (PEO) was examined by small-angle
      X-ray scattering (SAXS) and isothermal titration calorimetric techniques. The
      critical aggregation concentration values (cac), the saturation concentration
      (C(2)), the integral enthalpy change for aggregate formation (DeltaH(agg)(int))
      and the standard free energy change of micelle adsorption on the macromolecule
      chain (DeltaDeltaG(agg)) were derived from the calorimetric titration curves. In
      the presence of 1.00 mmol L(-1) cosolute, no changes in the parameters were
      observed when compared with those obtained for SDS-PEO interactions in pure
      water. For NaCl, Na(2)SO(4), Li(2)SO(4), and NaSCN at 10.0 and 100 mmol L(-1),
      the cosolute presence lowered cac, increased C(2), and the PEO-SDS aggregate
      became more stable. In the presence of Na(2)[Fe(CN)(5)NO], the calorimetric
      titration curves changed drastically, showing a possible reduction in the PEO-SDS
      degree of interaction, possibility disrupting the formed nanostructure; however,
      the SAXS data confirmed, independent of the small energy observed, the presence
      of aggregates adsorbed on the polymer chain.

PMID- 20806943
TI  - Development of novel pea protein-based nanoemulsions for delivery of
      nutraceuticals.
AB  - A novel pea protein-based emulsifier was used in the production of oil in water
      (O/W) nanoemulsions. The regions of kinetically stabilized O/W emulsions were
      individuated in a pseudoternary diagram containing different pea protein,
      sunflower oil, and water fractions. The stable O/W emulsion region was widened by
      the addition of NaCl to the aqueous phase or, to a more significant extent, by
      high pressure homogenization (HPH) processing. The HPH treatment caused the
      formation of very fine emulsions in the nanometric range (<200 nm), with
      extremely high stability over time. HPH treatment affected the protein
      properties, resulting in a reduced water surface tension. Changes in protein
      structure, which were characterized by light scattering and SDS-PAGE, suggest the
      occurrence of the disruption of disulfide bonds, thus changing the exposition and
      availability of hydrophobic groups.

PMID- 20806944
TI  - Influence of vibronic coupling on band structure and exciton self-trapping in
      alpha-perylene.
AB  - Exciton sizes influence transport processes and spectroscopic phenomena in
      molecular aggregates and crystals. Thermally driven nuclear motion generally
      localizes electronic states in equilibrium systems. Exciton sizes also undergo
      dynamic changes caused by nonequilibrium relaxation in the lattice structure
      local to the photoexcitations (i.e., self-trapping). The alpha-phase of
      crystalline perylene is particularly well-suited for fundamental studies of
      exciton self-trapping mechanisms. It is generally agreed that a subpicosecond
      self-trapping process in alpha-perylene localizes photoexcited excitons onto
      pairs of closely spaced molecules (i.e., dimers), which then relax through
      excimer emission. Here, electronic relaxation dynamics in alpha-perylene single
      crystals are investigated using a variety of nonlinear optical spectroscopies in
      conjunction with a Frenkel exciton model. Linear absorption and photon echo
      spectroscopies suggest that excitons are delocalized over less than four unit
      cells (16 molecules) at 78 K prior to self-trapping. Stimulated Raman
      spectroscopies conducted on and off electronic resonance reveal significant
      vibronic coupling in a mode at 104 cm(-1), which corresponds to the displacement
      between perylene molecules comprising a dimer. Strong vibronic coupling in this
      mode suggests that motion along the interdimer axis is instrumental in driving
      the self-trapping process. The results are discussed in the context of our recent
      study of tetracene and rubrene single crystals in which similar experiments and
      models were employed.

PMID- 20806945
TI  - Comparative study of the self-aggregation of rhodamine 6G in the presence of
      poly(sodium 4-styrenesulfonate), poly(N-phenylmaleimide-co-acrylic acid),
      poly(styrene-alt-maleic acid), and poly(sodium acrylate).
AB  - The interaction between rhodamine 6G and different polyelectrolytes is analyzed.
      Structural aspects differentiate these polyelectrolytes, such as the presence of
      aromatic groups and the number and localization of their respective charges,
      which may be directly attached to the aromatic groups or to the polymeric main
      chain. In the case of poly(sodium acrylate), which does not bear aromatic groups,
      the polyelectrolyte induces cooperative self-stacking between the dyes which is
      highly sensitive to the ionic strength, due to the predominance of long-range
      electrostatic interactions between the polymer and the dye. In the case of
      poly(sodium 4-styrenesulfonate), whose charge is directly attached to the
      aromatic groups, a high dispersant ability of the dyes is found and the
      interaction is less dependent on the ionic strength, due to the predominance of
      short-range aromatic-aromatic interactions between the dye and the polymer. Among
      the two polyelectrolytes studied for which the polymeric charge is directly
      attached to the main chain, and separated from the aromatic group, poly(styrene
      alt-maleic acid) shows a lower dependence of the interaction on the ionic
      strength than poly(N-phenylmaleimide-co-acrylic acid) at a comonomer composition
      of 1:2, due to a higher linear aromatic density and a lower linear charge
      density, indicating the importance of hydrophobic forces. Both copolymers exhibit
      a high ability to induce cooperative self-aggregation of the dye.

PMID- 20806946
TI  - Ultrafast dynamics of the excited states of curcumin in solution.
AB  - Dynamics of the excited singlet (S(1)) state of curcumin has been investigated in
      a wide varieties of solvents using subpicosecond time-resolved fluorescence and
      absorption spectroscopic techniques. As a consequence of extra stability of the
      cis-enol conformer due to the presence of an intramolecular hydrogen bond, it is
      the major form existing in the ground-state and the excited-state processes
      described here has been attributed to this form. Steady-state absorption and
      fluorescence spectra suggest significant perturbation of the intramolecular
      hydrogen bond and the possibility of formation of intermolecular hydrogen-bonded
      complex with the hydrogen-bonding solvents. Both the time-resolved techniques
      used here reveal that solvation is the major process contributing to the
      relaxation dynamics of the S(1) state. Solvation dynamics in protic solvents is
      multimodal, and the linear correlation between the longest component of the
      solvation process and the longitudinal relaxation time of the solvent suggests
      the specific hydrogen-bonding interaction between the solute and the solvent.
      However, a good correlation between the experimentally determined average
      solvation time and that predicted by the dielectric continuum model in all kinds
      of solvents also suggests that the dielectric relaxation of the solvent is also
      an important contributor to the solvation process. The lifetime of the S(1) state
      is very short in nonpolar solvents (~44 ps in 1,4-dioxane) because of efficient
      nonradiative deactivation of the S(1) state, which is an important consequence of
      the ultrafast excited-state intramolecular hydrogen transfer (ESIHT) reaction in
      the six-membered hydrogen-bonded chelate ring of the cis-enol form. However, it
      has not been possible to monitor the ESIHT reaction in real time because of the
      symmetrical structure of the molecule with respect to the hydrogen-bonded chelate
      ring. In polar solvents, dipole-dipole interaction perturbs the intramolecular
      hydrogen bond leading to the reduced efficiency of the nonradiative deactivation
      process. However, stretching vibration in the intermolecular hydrogen bonds
      formed in the hydrogen-bonding (both donating and accepting) solvents induces
      another efficient channel for the nonradiative relaxation of the S(1) state of
      curcumin.

PMID- 20806947
TI  - Effect of lipophilic tail architecture and solvent engineering on the structure
      of trehalose-based nonionic surfactant reverse micelles.
AB  - We use small-angle X-ray scattering and dynamic light scattering to investigate
      the structural and dynamical properties of trehalose polyisostearate, abbreviated
      as TQ-n (n = 3, 5, and 7), in different organic solvents, where n represents the
      number of isosterate chains per surfactant molecule. TQ-n spontaneously assembles
      into reverse micelles without addition of water at 25  degrees C. We found that
      for TQ-5 and TQ-7, steric hindrance of the lipophilic surfactant tail causes
      significant reduction of the aggregation number, whose scheme is clearly
      distinguished from the modification of the critical packing parameter. Increasing
      the hydrocarbon chain length of oils from octane to hexadecane favors one
      dimensional micellar growth, leading to the formation of rodlike micelles due to
      different penetration tendencies of oils into the lipophilic shell of the
      surfactant. Subtle differences in solvent polarity also plays a crucial role in
      the micellar size, which is decreased when liquid paraffin is replaced with
      squalene. A further decrease is attained in more polar mixed triglyceride oils. A
      rising temperature also results in the same direction. The extrapolated structure
      factor to the zero scattering vector, S(q -> 0), for the TQ-3/decane systems
      almost exactly follows that predicted for hard spheres, demonstrating that
      osmotic compressibility of the system is well explained if accounting for the
      excluded volume. However, we found that the effective diffusion coefficient
      decreases with surfactant concentration, which is an opposite trend to what is
      expected for hard spheres. This apparent contradiction is likely to be due to the
      occurrence of transient interdigitation between the lipophilic tails of
      neighboring reverse micelles at higher concentration. Our data highlight the
      relevance of the concept of "tunable reverse micellar geometry" in the novel
      trehalose-based nonionic surfactant binary mixtures, in which lipophilic tail
      architecture, solvent engineering, concentration, and temperature act as
      intrinsic parameters for the structure control of the reverse micelles.

PMID- 20806949
TI  - Coordination-induced switchable nanoparticle formation from naphthyl-bridged
      bis(beta-cyclodextrin).
AB  - Naphthyl-bridge bis(beta-cyclodextrin) (1) was synthesized via "click chemistry",
      and its self-assembly behavior was investigated by NMR, UV-vis, circular
      dichroism spectra, transmission electron microscopy, and atomic force microscopy.
      The results obtained indicate that the coordination of Hg(2+) with triazole rings
      in 1 induces the naphthyl moiety to move from being a self-included complex to
      the formation of nanoparticles through intermolecular self-aggregation.
      Furthermore, the formation and disassembly of nanoparticle was reversibly
      controlled by adding or removing Hg(2+).

PMID- 20806950
TI  - Diastereoselective conjugate addition of organocuprates to chiral N-enoyl
      oxazolidinethiones.
AB  - Addition of organocuprates, generated in situ using an excess of a 1:2 mixture of
      CuI.DMS and Grignard reagent, to N-enoyl oxazolidinethiones in the presence of
      excess TMSI gave preferentially the anti diastereomer where the addition took
      place when the conformation of the substrate was syn-s-cis. The reaction was
      investigated with indene-based and three different phenyl glycine derived
      oxazolidinethiones.

PMID- 20806948
TI  - Chelation-assisted, copper(II)-acetate-accelerated azide-alkyne cycloaddition.
AB  - We described in a previous communication a variant of the popular Cu(I)-catalyzed
      azide-alkyne cycloaddition (AAC) process where 5 mol % of Cu(OAc)(2) in the
      absence of any added reducing agent is sufficient to enable the reaction. 2
      Picolylazide (1) and 2-azidomethylquinoline (2) were found to be by far the most
      reactive carbon azide substrates that convert to 1,2,3-triazoles in as short as a
      few minutes under the discovered conditions. We hypothesized that the abilities
      of 1 and 2 to chelate Cu(II) contribute significantly to the observed high
      reaction rates. The current work examines the effect of auxiliary ligands near
      the azido group other than pyridyl for Cu(II) on the efficiency of the Cu(OAc)(2)
      accelerated AAC reaction. The carbon azides capable of binding to the catalytic
      copper center at the alkylated azido nitrogen in a chelatable fashion were indeed
      shown to be superior substrates under the reported conditions. The chelation
      between carbon azide 11 and Cu(II) was demonstrated in an X-ray single-crystal
      structure. In a limited set of examples, the ligand
      tris(benzyltriazolylmethyl)amine (TBTA), developed by Fokin et al. for assisting
      the original Cu(I)-catalyzed AAC reactions, also dramatically enhances the
      Cu(OAc)(2)-accelerated AAC reactions involving nonchelating azides. This
      observation leads to the hypothesis of an additional effect of chelating azides
      on the efficiencies of Cu(OAc)(2)-accelerated AAC reactions, which is to
      facilitate the rapid reduction of Cu(II) to highly catalytic Cu(I) species.
      Mechanistic studies on the AAC reactions with particular emphasis on the role of
      carbon azide/copper interactions will be conducted based on the observations
      reported in this work. Finally, the immediate utility of the product 1,2,3
      triazole molecules derived from chelating azides as multidentate metal
      coordination ligands is demonstrated. The resulting triazolyl-containing ligands
      are expected to bind with transition metal ions via the N(2) nitrogen of the
      1,2,3-triazolyl group to form nonplanar coordination rings. The Cu(II) complexes
      of bidentate T1 and tetradentate T6 and the Zn(II) complex of T6 were
      characterized by X-ray crystallography. The structure of
      [Cu(T1)(2)(H(2)O)(2)](ClO(4))(2) reveals the interesting synergistic effect of
      hydrogen bonding, pi-pi stacking interactions, and metal coordination in forming
      a one-dimensional supramolecular construct in the solid state. The tetradentate
      coordination mode of T6 may be incorporated into designs of new molecule sensors
      and organometallic catalysts.

PMID- 20806951
TI  - 6-Thioguanine and S6-methylthioguanine are mutagenic in human cells.
AB  - Thiopurines are effective immunosuppressants and anticancer agents. However, the
      long-term use of thiopurines was found to be associated with a significantly
      increased risk of various types of cancer. To date, the specific mechanism(s)
      underlying the carcinogenicity associated with thiopurine treatment remain(s)
      unclear. Herein, we constructed duplex pTGFP-Hha10 shuttle vectors carrying a 6
      thioguanine ((S)G) or S6-methylthioguanine (S6mG) at a unique site and allowed
      the vectors to propagate in three different human cell lines. Analysis of the
      replication products revealed that although neither thionucleoside blocked
      considerably DNA replication in any of the human cell lines, both (S)G and S6mG
      were mutagenic, resulting in G->A mutation at frequencies of ~8% and ~39%,
      respectively. Consistent with what was found from our previous study in E. coli
      cells, our data demonstrated that the mutagenic properties of (S)G and S6mG
      provided significant evidence for mutation induction as a potential carcinogenic
      mechanism associated with chronic thiopurine intervention.

PMID- 20806952
TI  - Prominent effect of alkali metals in halogen-bonded complex of MCCBr-NCM' (M and
      M' = H, Li, Na, F, NH2, and CH3).
AB  - Quantum chemical calculations have been performed for the MCCBr-NCM' (M and M' =
      H, Li, Na, F, NH2, and CH3) halogen-bonded complexes at the MP2/aug-cc-pVTZ
      level. The binding energy is in a range of 1.34-23.42 kJ/mol. The results show
      that the alkali metal has a prominent effect on the strength of halogen bond, and
      this effect is different for the alkali metal in the halogen and electron donors.
      The alkali atom in the halogen donor makes it weaken greatly, whereas that in the
      electron donor causes it to enhance greatly. Natural bond orbital analysis shows
      that the alkali atom is electron-withdrawing in the halogen donor and electron
      donating in the electron donor. In formation of the halogen bond, the former is a
      negative contribution, whereas the latter is a positive one. A similar charge
      transfer is also found for the H atom in the halogen and electron donors. These
      complexes have also been analyzed with the atoms in molecules theory.

PMID- 20806953
TI  - Transition-metal-free homocoupling of 1-haloalkynes: a facile synthesis of
      symmetrical 1,3-diynes.
AB  - Symmetrical 1,3-diyne compounds can be easily synthesized via a transition-metal
      free homocoupling reaction of 1-haloalkynes without base and oxidant. The method
      shows excellent functional group compatibility and high yields.

PMID- 20806954
TI  - Structural and thermodynamic characteristics of the exosite binding pocket on the
      human BACE1: a molecular modeling approach.
AB  - We report a molecular modeling study aimed to locate and provide the full
      structural characteristics of the exosite binding site of the BACE1. A three-step
      procedure was followed. In the first stage, we performed blind docking studies on
      the whole target surface. In a second stage, the mode of binding was further
      refined by molecular dynamics (MD) simulation. Finally, binding free energy
      calculations, through the MM-PBSA protocol, were carried out to gain insight into
      the stability and thermodynamics of the inhibitor located at the selected binding
      pockets. Twelve binding pockets were identified on the surface of BACE1 by blind
      docking studies. The calculations of binding free energies for the 12 complexes
      show that van der Waals interactions dominate the mode of binding of these
      complexes. The best ranked complex shows that residues Glu255-Pro258, Phe261,
      Gly264-Ala272, Asp311-Ala313, Ser315, and Asp317-Tyr320 are located within 6 A
      from the INH located at the exosite. The hydrogen bonds formed between the INH
      peptide, residues Tyr1, Tyr3, and Leu7 with the BACE1 residues Leu267, Cys269,
      Trp270, Asp311, and Asp 317 can strengthen the binding of the BACE1-INH complex.

PMID- 20806955
TI  - Modeling the charge transfer between alkali metals and polycyclic aromatic
      hydrocarbons using electronic structure methods.
AB  - The interaction of alkali metals-specifically, lithium-with polycyclic aromatic
      hydrocarbons (PAHs) was studied using a variety of electronic structure methods.
      Electron transfer from lithium to a PAH depends on the size and structure of the
      PAH and the electronic structure method used. In some cases, we observe an
      artificial transfer when using density functional theory (DFT) due to the self
      interaction error, whereas Hartree-Fock underestimates the amount of charge
      transfer due to overlocalization. Our results have interesting implications for
      the validity of DFT calculations on the alkali metal-PAH interaction in Li
      batteries, hydrogen storage devices, and alkali-metal-doped superconductors.

PMID- 20806956
TI  - Catalytic dehydrocoupling/dehydrogenation of N-methylamine-borane and ammonia
      borane: synthesis and characterization of high molecular weight polyaminoboranes.
AB  - The catalytic dehydrocoupling/dehydrogenation of N-methylamine-borane,
      MeNH(2).BH(3) (7), to yield the soluble, high molecular weight poly(N
      methylaminoborane) (8a), [MeNH-BH(2)](n) (M(W) > 20 000), has been achieved at 20
      degrees C using Brookhart's Ir(III) pincer complex IrH(2)POCOP (5) (POCOP =
      [MU(3)-1,3-(OPtBu(2))(2)C(6)H(3)]) as a catalyst. The analogous reaction with
      ammonia-borane, NH(3).BH(3) (4), gave an insoluble product, [NH(2)-BH(2)](n)
      (8d), but copolymerization with MeNH(2).BH(3) gave soluble random copolymers,
      [MeNH-BH(2)](n)-r-[NH(2)-BH(2)](m) (8b and 8c). The structures of polyaminoborane
      8a and copolymers 8b and 8c were further analyzed by ultrahigh resolution
      electrospray mass spectrometry (ESI-MS), and 8a, together with insoluble
      homopolymer 8d, was also characterized by (11)B and (1)H solid-state NMR, IR, and
      wide-angle X-ray scattering (WAXS). The data indicate that 8a-8c are essentially
      linear, high molecular weight materials and that the insoluble polyaminoborane 8d
      possesses a similar structure but is of lower molecular weight (ca. 20 repeat
      units), presumably due to premature precipitation during its formation. The yield
      and molecular weight of polymer 8a was found to be relatively robust toward the
      influence of different temperatures, solvents, and adduct concentrations, while
      higher catalyst loadings led to higher molecular weight materials. It was
      therefore unexpected that the polymerization of 7 using 5 was found to be a chain
      growth rather than a step-growth process, where high molecular weights were
      already attained at about 40% conversion of 7. The results obtained are
      consistent with a two stage polymerization mechanism where, first, the Ir
      catalyst 5 dehydrogenates 7 to afford the monomer MeNH?BH(2) and, second, the
      same catalyst effects the subsequent polymerization of this species. A wide range
      of other catalysts based on Ru, Rh, and Pd were also found to be effective for
      the transformation of 7 to polyaminoborane 8a. For example, polyaminoborane 8a
      was even isolated from the initial stage of the dehydrocoupling/dehydrogenation
      of 7 with [Rh(MU-Cl)(1,5-cod)](2) (2) as the catalyst at 20  degrees C, a
      reaction reported to give the N,N,N-trimethyl borazine, [MeN-BH](3), under
      different conditions (dimethoxyethane, 45  degrees C). The ability to use a
      variety of catalysts to prepare polyaminoboranes suggests that the synthetic
      strategy should be applicable to a broad range of amine-borane precursors and is
      a promising development for this new class of inorganic polymers.

PMID- 20806957
TI  - A molecular quantized charge pump.
AB  - A novel single electron pump based on individual molecules (a single wall carbon
      nanotube) is discussed in terms of the hybrid superconducting-normal conducting
      pumping principle. A concept demonstration device has been built based on a
      carbon nanotube contacted by Nb-Ti leads. Charge current quantization is achieved
      through rf modulation of the back gate voltage. The device is able to transfer a
      given number of electrons per pumping cycle. Single electron pumping is achieved
      for pumping frequencies up to 80 MHz.

PMID- 20806958
TI  - Theoretical and experimental study of the effectiveness of the 5-pyrimidyl
      tetrazolate bridging ligand in mediating magnetic exchange interactions.
AB  - The 5-pyrimidyl-tetrazolate anion (pmtz) has six basic nitrogen atoms and,
      consequently, can exhibit a variety of bridging coordination modes. This ligand
      reacts with either copper(II) and nickel(II) ions in the presence of bi- and
      tridentate amines to afford the following pmtz-bridged complexes: [Cu(4)(MU
      pmtz)(4)(tmda)(4)](ClO(4))(4) (1) (tmda = N,N,N',N'-tetramethylethylenediamine),
      [Cu(2)(MU-pmtz)(tren)(2)](ClO(4))(3) (2) (tren = tris(2-aminoethyl)amine),
      [Ni(2)(MU-pmtz)(tren)(2)](ClO(4))(3) (3), and [Ni(2)(MU
      pmtz)(2)(ampa)(2)](n)(SCN)(2n) (ampa = bis(3-aminopropyl)amine) (4). The
      structure and bridging coordination mode of these complexes depend on the
      stereoelectronic preferences of the metal ion and the coordination properties of
      the polyamine (denticity and relative disposition of the donor atoms). Thus,
      complex 1 is a square tetranuclear compound where the ligand adopts an asymmetric
      k(2)N(1),N(7):k(2)N(4),N(11) bis(chelating)/bridging mode. Complexes 2 and 3 are
      dinuclear species. In the former the pmtz exhibits a novel k-N(1):k-N(4)
      imidazolyl/bridging mode whereas the latter shows a symmetric
      k(2)N(1),N(7):k(2)N(4),N(11) bis(chelating)/bridging mode. Complex 4 exhibits,
      however, a linear chain structure where the pmtz ligand connects neighboring
      nickel(II) atoms by using a tridentate k(2)N(1),N(7):kN(3) chelating/bridging
      mode. Variable-temperature magnetic susceptibility studies reveal that complexes
      1-4 show weak to moderate antiferromagnetic (AF) coupling between the metal ions
      through the pmtz ligand with J = -14.1 cm(-1) for 1, J = -31.1 cm(-1) for 2, J = 
      4.09 cm(-1) for 3, and J = -8.7 cm(-1) for 4. The magneto-structural results, as
      well as DFT theoretical calculations carried out on the experimental geometries
      and model complexes, demonstrate, first, that the magnitude of the AF interaction
      observed for imidazolyl pmtz-bridged complexes mainly depends on the Cu-N-C angle
      (the greater the Cu-N-C angle, the stronger is the AF interaction) and, second,
      that the tridentate chelating/bridging mode is more effective in mediating AF
      exchange interactions than the bis(chelating)/bridging or imidazolyl/bridging
      modes in pmtz-bridged complexes.

PMID- 20806959
TI  - In situ electrical monitoring of cation exchange in nanowires.
AB  - Controlling the extent of cation exchange reactions is a promising route for
      tuning the material composition and properties of nanostructures. Here we
      demonstrate how measuring the conductivity of nanowires during cation exchange
      can be used to monitor the transition from CdSe to Ag(2)Se, in situ. In addition,
      by imaging the same wire mat region before and after complete cation exchange, we
      find that the shape and morphology of the nanowires are completely preserved.

PMID- 20806960
TI  - Ecosystem-based assessment indices of restoration for Daya Bay near a nuclear
      power plant in South China.
AB  - China has adopted nuclear power generation as one of the strategic energy sources
      to resolve the dilemma between its ever-growing energy demand and the associated
      environmental issues. To achieve the latter, a systematic assessment of the state
      of the ecosystem near nuclear power plants and its restoration via ongoing
      recovery actions would be highly desirable and much needed. Current assessment
      methods are mostly based on the individual components of the ecosystem and the
      methods are therefore not integrated. In this paper, we report a set of system
      based assessment indices to study the restoration of Daya Bay in Guangdong, China
      where a nuclear power plant has been in operation for 15 years. The results show
      that decades of intensive exploitation by the various coastal activities have
      pushed Daya Bay's ecosystem away from its baseline and its structure and
      functions are impaired; ecosystem restoration does not make up for the weakening
      of the ecological carrying capacity due to anthropogenic sea-use, nonetheless,
      the potential for recovery still exists. The case study suggests that the system
      based indices can provide integrated information for ecosystem restoration
      assessment and management.

PMID- 20806961
TI  - Surface reaction mechanisms during ozone and oxygen plasma assisted atomic layer
      deposition of aluminum oxide.
AB  - We have elucidated the reaction mechanism and the role of the reactive
      intermediates in the atomic layer deposition (ALD) of aluminum oxide from
      trimethyl aluminum in conjunction with O(3) and an O(2) plasma. In situ
      attenuated total reflection Fourier transform infrared spectroscopy data show
      that both -OH groups and carbonates are formed on the surface during the
      oxidation cycle. These carbonates, once formed on the surface, are stable to
      prolonged O(3) exposure in the same cycle. However, in the case of plasma
      assisted ALD, the carbonates decompose upon prolonged O(2) plasma exposure via a
      series reaction kinetics of the type, A (CH(3)) --> B (carbonates) --> C
      (Al(2)O(3)). The ratio of -OH groups to carbonates on the surface strongly
      depends on the oxidizing agent, and also the duration of the oxidation cycle in
      plasma-assisted ALD. However, in both O(3) and O(2) plasma cycles, carbonates are
      a small fraction of the total number of reactive sites compared to the hydroxyl
      groups.

PMID- 20806962
TI  - One more extreme near the critical micelle concentration: optical activity.
AB  - It is reported the discovery of optical activity of micellar solutions of sodium
      dodecyl sulfate, cetyltrimethylammonium bromide, and poly(oxyethilene)(4)dodecyl
      ether as typical representatives of anionic, cationic, and nonionic surfactants.
      The surfactants exhibit dextrorotation. Since the optical activity of the ionic
      surfactants appears only above the Krafft point, it should be ascribed to
      micellar aggregates. Optical rotation as a function of the surfactant
      concentration displays a pronounced maximum near the critical micelle
      concentration (the subsequent decrease of optical activity corresponds to
      formation of spherical micelles that cannot possess optical activity by
      symmetry). For sodium dodecyl sulfate, the maximum correlates well with extremes
      of other properties of surfactant solutions (foaminess, foam stability, Gibbs'
      and transversal elasticity of thin foam films), which was described earlier.
      Naturally, films and foams of sodium dodecyl sulfate solutions also demonstrate
      optical activity.

PMID- 20806963
TI  - Preparation and characterization of a solid amine adsorbent for capturing CO2 by
      grafting allylamine onto PAN fiber.
AB  - Solid amine adsorbents using synthetic fibers instead of silica as the matrix are
      expected to offer more benefits for the adsorption of CO(2) because of high
      external surface area, low pressure drops, and flexibility of the matrix fibers.
      A novel kind of solid amine-containing fibrous adsorbent (PAN-AF) was prepared by
      preirradiation grafting copolymerization of allylamine onto polyacrylonitrile
      (PAN) fiber, using the redox system of (NH(4))(2)S(2)O(8)/NaHSO(3) as initiator.
      The effects of the reaction conditions such as reaction time, temperature,
      monomer concentration, amount of the initiator on grafting degree were studied.
      The results showed that the optimal conditions for the grafting copolymerization
      were using 50% allylamine monomer (V/V) and 1.5% (W/V) initiator and reacting at
      100 degrees C for 10 h. FTIR was employed to characterize the corresponding
      changes on the surface chemical structure of PAN and PAN-AF. Thermal gravimetric
      analysis was used to evaluate the thermal stability of the materials. Equilibrium
      adsorption capacities for CO(2) and regeneration behaviors of PAN-AF were
      determined. Adsorption capacity for CO(2) of PAN-AF with 60.0 wt % grafting
      degree was 6.22 mmol CO(2)/g PAN-AF. PAN-AF could be completely regenerated by
      heating in boiling water for 30 min. The CO(2) adsorption performance of the
      regenerated PAN-AF was almost the same as that of the fresh adsorbent after
      several cycles, which revealed that PAN-AF exhibited good regenerating stability.
      The high speed and effective regeneration process proves that PAN-AF has great
      potential in industrial applications for CO(2) capture.

PMID- 20806964
TI  - Photoswitching behavior of azobenzene-containing alkanethiol self-assembled
      monolayers on Au surfaces.
AB  - The photoisomerization of self-assembled monolayers of azobenzene-containing
      alkanethiols, as well as of mixed monolayers of these substances with n
      alkanethiol spacer molecules on Au surfaces, was studied by photoelectrochemical
      measurements and surface plasmon resonance spectroscopy. A strong dependence on
      the molecular structure of the adsorbates was found, specifically on the linker
      between the azobenzene moiety and the alkanethiol: while molecules with an amide
      group were photoinactive, those with an ether group exhibited pronounced,
      reversible photoisomerization in pure and mixed adlayers. Both trans-cis and cis
      trans isomerization followed first-order kinetics with time constants that
      suggest high quantum efficiencies for these processes.

PMID- 20806965
TI  - Measuring the influence of solution chemistry on the adhesion of au nanoparticles
      to mica using colloid probe atomic force microscopy.
AB  - Engineered nanoparticles are used increasingly in numerous commercial products,
      leading to concerns over their environmental fate and ecotoxicity. We report the
      adaptation of colloid probe atomic force microscopy (AFM) to quantitatively
      determine the adhesive behavior of gold nanoparticles (Au NPs) with mica, chosen
      as a model for sand, in various water chemistries. Au NP-covered polystyrene (PS)
      beads were prepared by a combined swelling-heteroaggregation (CSH) technique
      prior to attachment to tipless AFM cantilevers. Force measurements were performed
      over a range of solution conditions (pH, ionic strength (IS), and natural organic
      matter (NOM) content). Plain PS beads with no Au NPs were used as controls. In
      general, adhesion of Au NP-PS beads to mica were found to increase as IS
      increased while a rise in pH led to a decrease in adhesion. Plain PS beads were
      not observed to adhere to mica in any of the experimental solution conditions,
      and the PS force curves were unaffected by changes in the pH and electrolyte
      concentrations. In the presence of NOM, pull-off forces for Au NP-PS beads
      increased in magnitude when NaCl was added. In addition, the experimental
      approach force curves were not successfully described by the classical Derjaguin
      Landau-Verwey-Overbeek (DLVO) theory of colloidal stability. To reconcile the
      discrepancy between theory and experiment, an extended DLVO (xDLVO) empirical
      model was used to account for the contribution of non-DLVO interactions (known
      collectively as structural forces) between the Au NPs and mica surfaces.

PMID- 20806966
TI  - Size matters: incorporation of poly(acrylic acid) and small molecules into
      hierarchically porous metal oxides prepared with and without templates.
AB  - Template synthesis of metal oxides can create materials with highly controlled
      and reproducible pore structures that can be optimized for particular
      applications. Zirconium titanium oxides (25:75 mol %) with three different pore
      structures were synthesized in order to relate polymer loading capacity to
      macropore architecture. Sol-gel chemistry was used to prepare the materials in
      conjunction with (i) agarose gel templating, (ii) no template, and (iii) stearic
      acid templating. The three materials possessed high surface areas (212-316 m(2)
      g(-1)). Surface modification was performed postsynthetically using propionic acid
      (a monomer), glutaric acid (a dimer), and three molecular weights of poly(acrylic
      acid) (2000, 100,000, and 250,000 g mol(-1)). Higher loading (mg g(-1)) was
      observed for the polymers than for the small molecules. Following surface
      modification, a perceptible decrease in surface area and mesopore volume was
      noted, but both mesoporosity and macroporosity were retained. The pore
      architecture had a strong bearing on the quantity and rate of polymer
      incorporation into metal oxides. The templated pellet with hierarchical porosity
      outperformed the nontemplated powder and the mesoporous monolith (in both loading
      capacity and surface coverage). The materials were subjected to irradiation with
      (60)Co gamma-rays to determine the radiolytic stability of the inorganic support
      and the hybrid material containing the monomer, dimer, and polymer. The polymer
      and the metal oxide substrate demonstrated notable radiolytic stability.

PMID- 20806967
TI  - Fabrication of complex patterns with a wide range of feature sizes from a single
      line prepattern by successive application of capillary force lithography.
AB  - The variously shaped gold patterns can be generated from the polydimethylsiloxane
      (PDMS) mold using line patterns by the capillary force lithography (CFL) process,
      which is a kind of nanoimprint method following the two-cycle method. After
      fabrication of micro- or nanosized line patterns at the first cycle, the
      patterned substrate is used as a substrate for the second cycle of CFL. When the
      other stamp is placed on the first pattern, rotated by a certain angle with
      respect to the first stamp, only the overlapped parts remained dot-shaped after
      the etching process. The various shapes and sizes of patterns can be produced by
      controlling the CFL conditions such as polymer thickness, reactive ion etching
      (RIE) time, and degree of rotation angle. The key advantage of the double imprint
      lithography method is to get the nanosized isolated dot-shaped patterns from
      microsized line patterns. If we fabricate nanosized isolated dot-shaped patterns
      directly, we should need predesigned patterns in the form of a master, which is
      generally prepared by a high-cost and time-consuming process such as E-beam
      lithography. The successful applications of large-area periodic patterns are
      nanoelectronic devices, nanoelectromechanical system (NEMS), and biosensors, the
      template of which is the master of nanoimprint lithography (NIL) and stamp
      fabrication in soft lithography.

PMID- 20806969
TI  - Stathmin, a new target of PRL-3 identified by proteomic methods, plays a key role
      in progression and metastasis of colorectal cancer.
AB  - To better understand the role of PRL-3 in progression and metastasis of
      colorectal cancer (CRC), we searched for PRL-3 associated proteins using
      proteomic methods. We identified 39 PRL-3 associated proteins based on proteomic
      strategy. Stathmin, a key oncoprotein, was proved to be a new PRL-3 associated
      protein. Notably, co-immunoprecipitation assays in both endogenous CRC cell lines
      and CRC tissues indicated that PRL-3 could interact with stathmin. And, both
      stathmin and PRL-3 contributed to microtubule (MT) destabilization of CRC cells.
      Moreover, gain-of-function and loss-of-function analyses revealed that stathmin
      promoted proliferation, cell adhesion, and migration of human CRC cells.
      Immunohistochemical analysis of 149 colorectal tumor samples showed that
      overexpression of stathmin was strongly correlated with tumor differentiation (P
      = 0.035), tumor invasion (P = 0.024), lymph node status (P < 0.001), Dukes
      classification (P < 0.001), and TNM staging (P < 0.001) of CRC patients.
      Univariate and multivariate survival analyses further supported that
      overexpression of stathmin protein was a potential independent poor prognostic
      factor for CRC. Our results reveal many PRL-3 associated proteins for the first
      time. The oncoprotein stathmin plays a key role in CRC as a new target of PRL-3.
      Interaction between PRL-3 and stathmin leads to MT destabilization of CRC cells,
      which contributes to progression and metastasis of CRC.

PMID- 20806970
TI  - Aptamer microarray mediated capture and mass spectrometry identification of
      biomarker in serum samples.
AB  - Sensitive detection of molecular biomarkers in clinical samples is crucially
      important in disease diagnostics. This paper reports the development of an
      aptamer microarray platform combined with sol-gel technology to identify low
      abundance targets in complex serum samples. Because of the nanoporous structure
      of the sol-gel, a high capacity to immobilize the affinity specific aptamers is
      accomplished which allows binding and detection of target molecules with high
      sensitivity. The captured protein is digested in situ and the obtained digest was
      analyzed by ESI-MS without any interference from the affinity probe. TBP (TATA
      Box Protein) and its specific aptamers were chosen as a model system. A proof of
      concept with protein concentrations ranging between nanomolar to micromolar is
      reported, showing a good linearity up to 400 nM when characterized in an aptamer
      sandwich assay. Moreover, as low as 0.001% of target protein present in total
      serum proteins could be identified without any pretreatment step using ESI MS/MS
      mass spectrometry. We believe this novel strategy could become an efficient
      method for aptamer-based biomarker detection linked directly to mass spectrometry
      readout.

PMID- 20806971
TI  - Discovery of novel bladder cancer biomarkers by comparative urine proteomics
      using iTRAQ technology.
AB  - A urine sample preparation workflow for the iTRAQ (isobaric tag for relative and
      absolute quantitation) technique was established. The reproducibility of this
      platform was evaluated and applied to discover proteins with differential levels
      between pooled urine samples from nontumor controls and three bladder cancer
      patient subgroups with different grades/stages (a total of 14 controls and 23
      cancer cases in two multiplex iTRAQ runs). Combining the results of two
      independent clinical sample sets, a total of 638 urine proteins were identified.
      Among them, 55 proteins consistently showed >2-fold differences in both sample
      sets. Western blot analyses of individual urine samples confirmed that the levels
      of apolipoprotein A-I (APOA1), apolipoprotein A-II, heparin cofactor 2 precursor
      and peroxiredoxin-2 were significantly elevated in bladder cancer urine specimens
      (n = 25-74). Finally, we quantified APOA1 in a number of urine samples using a
      commercial ELISA and confirmed again its potential value for diagnosis (n = 126,
      94.6% sensitivity and 92.0% specificity at a cutoff value of 11.16 ng/mL) and
      early detection (n = 71, 83.8% sensitivity and 94.0% specificity). Collectively,
      our results provide the first iTRAQ-based quantitative profile of bladder cancer
      urine proteins and represent a valuable resource for the discovery of bladder
      cancer markers.

PMID- 20806972
TI  - Variation of some fermentative sulfur compounds in Italian "millesime" classic
      sparkling wines during aging and storage on lees.
AB  - Fermentative sulfur compounds are recognized as strongly affecting wine aroma,
      mainly as off-flavors, but recently also as possible positive contributors to
      wine quality and typicity in still wines. Nevertheless, no evidence has been
      provided for the influence of these molecules on sparkling wine aroma, except for
      peculiar volatile thiols found in French Champagne. According to the traditional
      method, the second fermentation, occurring in sealed bottles, is the essence of
      the procedure. After this fermentation, sparkling wine is aged on yeast lees for
      a period ranging from a few months to several years so that yeast autolysis can
      take place. So far, no evidence is provided for the effect of yeast contact
      duration on the level of sulfur compounds. Following a HS-SPME/GC-MS method, 13
      sulfur compounds, that is, ethylmercaptan, dimethyl sulfide, diethyl sulfide,
      dimethyl disulfide, diethyl disulfide, methyl thioacetate, ethyl thioacetate, 2
      mercaptoethanol, 2-(methylthio)-1-ethanol, 3-(methylthio)-1-propanol, 4
      (methylthio)-1-butanol, benzothiazole, and 5-(2-hydroxyethyl)-4-methylthiazole,
      were quantified in several Italian sparkling wines, produced according to the
      traditional method in two wineries from Trentino-South Tyrol, region.
      Additionally, the influence of winemaking technology differences and vintage
      effects on the evolution of the quoted sulfur compounds was considered. This
      investigation was carried out by coupling the HS-SPME data with those obtained by
      SPE method and relevant to other volatile compounds, which are considered as
      winemaking markers. This work furnished the first evidence of the effect of aging
      and lees contact at different storage temperatures on the levels of these
      analytes in sparkling wines. Significant increments were observed for dimethyl
      sulfide, diethyl sulfide, 2-(methylthio)-1-ethanol, 3-(methylthio)-1-propanol,
      and 4-(methylthio)-1-butanol during aging with a different variation slope
      possibly due to the remarkably different storage temperatures. No clear influence
      of lees contact duration was found for the majority of the sulfur compounds
      considered.

PMID- 20806973
TI  - Effect of carrot (Daucus carota) microstructure on carotene bioaccessibility in
      the upper gastrointestinal tract. 2. In vivo digestions.
AB  - Nutrient bioaccessibility and subsequent absorption will be directly influenced
      by changes in food structure during gastrointestinal processing. The accompanying
      paper (Tydeman et al. J. Agric. Food Chem. 2010, 58, doi: 10.1021/jf101034a)
      reported results on the effect of carrot processing on the release of carotene
      into lipid phases during in vitro gastric and small intestinal digestions. This
      paper describes results from in vivo digestion of two of the types of processed
      carrot used previously, raw grated carrot and cooked carrot mashed to a puree.
      Ileostomy effluents from human volunteers fed meals containing the carrot
      material were used to study tissue microstructure and carotene release. Raw
      carrot shreds and intact cells that had survived the pureeing process were
      identifiable in ileal effluent. The gross tissue structure in the shreds had not
      changed following digestion. Carotene-containing particles remained encapsulated
      in intact cells, but were absent from ruptured cells. Microscopy revealed marked
      changes to the cell walls including swelling and pectin solubilization, which
      increased in severity with increasing residence time in the upper gut. These
      observations were entirely consistent with the in vitro observations. It was
      concluded that a single intact cell wall is sufficient to reduce carotene
      bioaccessibility from a cell by acting as a physical barrier, which is not broken
      down during upper gut digestion.

PMID- 20806974
TI  - A fresh look at road salt: aquatic toxicity and water-quality impacts on local,
      regional, and national scales.
AB  - A new perspective on the severity of aquatic toxicity impact of road salt was
      gained by a focused research effort directed at winter runoff periods. Dramatic
      impacts were observed on local, regional, and national scales. Locally, samples
      from 7 of 13 Milwaukee, Wisconsin area streams exhibited toxicity in Ceriodaphnia
      dubia and Pimephales promelas bioassays during road-salt runoff. Another
      Milwaukee stream was sampled from 1996 to 2008 with 72% of 37 samples exhibiting
      toxicity in chronic bioassays and 43% in acute bioassays. The maximum chloride
      concentration was 7730 mg/L. Regionally, in southeast Wisconsin, continuous
      specific conductance was monitored as a chloride surrogate in 11 watersheds with
      urban land use from 6.0 to 100%. Elevated specific conductance was observed
      between November and April at all sites, with continuing effects between May and
      October at sites with the highest specific conductance. Specific conductance was
      measured as high as 30,800 MUS/cm (Cl = 11,200 mg/L). Chloride concentrations
      exceeded U.S. Environmental Protection Agency (USEPA) acute (860 mg/L) and
      chronic (230 mg/L) water-quality criteria at 55 and 100% of monitored sites,
      respectively. Nationally, U.S. Geological Survey historical data were examined
      for 13 northern and 4 southern metropolitan areas. Chloride concentrations
      exceeded USEPA water-quality criteria at 55% (chronic) and 25% (acute) of the 168
      monitoring locations in northern metropolitan areas from November to April. Only
      16% (chronic) and 1% (acute) of sites exceeded criteria from May to October. At
      southern sites, very few samples exceeded chronic water-quality criteria, and no
      samples exceeded acute criteria.

PMID- 20806975
TI  - Chemo-resistant protein expression pattern of glioblastoma cells (A172) to
      perillyl alcohol.
AB  - Glioblastoma multiform (GBM) is by far the most malignant glioma. We have
      introduced a new treatment for GBMs that comprises the inhalation of a naturally
      occurring terpene with chemotherapeutic properties known as perillyl alcohol
      (POH). Clinical trial results on recurrent GBM patients showed that POH extends
      the average life by more than eight months, temporarily slows tumor growth, and
      in some cases even decreases tumor size. After approximately seven months, the
      tumor continues to grow and leads to a dismal prognosis. To investigate how these
      tumors become resistant to POH, we generated an A172 human glioblastoma cell
      culture tolerant to 0.06 mM of POH (A172r). We used Multidimensional Protein
      Identification Technology (MudPIT) to compare the protein expression profile of
      A172r cells to the established glioblastoma A172 cell line. Our results include a
      list of identified proteins unique to either the resistant or the nonresistant
      cell line. These proteins are related to cellular growth, negative apoptosis
      regulation, Ras pathway, and other key cellular functions that could be connected
      to the underlying mechanisms of resistance.

PMID- 20806976
TI  - Highly enantioselective catalytic dynamic resolution of N-Boc-2-lithiopiperidine:
      synthesis of (R)-(+)-N-Boc-pipecolic acid, (S)-(-)-coniine, (S)-(+)-pelletierine,
      (+)-beta-conhydrine, and (S)-(-)-ropivacaine and formal synthesis of (-)-lasubine
      II and (+)-cermizine C.
AB  - The catalytic dynamic resolution (CDR) of rac-2-lithio-N-Boc-piperidine using
      chiral ligand 8 or its diastereomer 9 in the presence of TMEDA has led to the
      highly enantioselective syntheses of both enantiomers of 2-substituted
      piperidines using a wide range of electrophiles. The CDR has been applied to the
      synthesis of (R)- and (S)-pipecolic acid derivatives, (+)-beta-conhydrine, (S)
      (+)-pelletierine, and (S)-(-)-ropivacaine and the formal synthesis of (-)
      lasubine II and (+)-cermizine C.

PMID- 20806977
TI  - Aryl C-H bond amination by an electrophilic diruthenium nitride.
AB  - Thermolysis of the terminal azido Ru(2)(D(3,5-Cl(2))PhF)(3)N(3) (3, D(3,5
      Cl(2))PhF = N,N'-bis(3,5-dichlorophenyl) formamidinate) cleanly produces
      Ru(2)[(D(3,5-Cl(2))PhF)(3)(D(3,5-Cl(2)-2-NH)PhF)] (4), which is proposed to
      result from insertion of a nitrido N atom into a ligand aryl C-H bond. This
      mechanism is supported by differential scanning calorimetry and thermogravimetric
      analysis results, which show the two-step reaction to be exothermic by -215 kJ
      mol(-1), in agreement with results from density functional theory calculations.
      This is the first example of electrophilic insertion of a terminal nitride into
      an aromatic C-H bond.

PMID- 20806979
TI  - Prediction and optimization of liquid propagation in micropillar arrays.
AB  - Prediction and optimization of liquid propagation rates in micropillar arrays are
      important for various lab-on-a-chip, biomedical, and thermal management
      applications. In this work, a semianalytical model based on the balance between
      capillary pressure and viscous resistance was developed to predict liquid
      propagation rates in micropillar arrays with height-to-period ratios greater than
      1 and diameter-to-period ratios less than 0.57. These geometries represent the
      most useful regimes for practical applications requiring large propagation rates.
      The capillary pressure was obtained using an energy approach where the meniscus
      shape was predicted using Surface Evolver simulations and experimentally verified
      by interference microscopy. The combined viscous resistance of the pillars and
      the substrate was determined using Brinkman's equation with a numerically
      obtained permeability and corroborated with finite element simulations. The model
      shows excellent agreement with one-dimensional propagation experiments of
      deionized water in silicon micropillar arrays, highlighting the importance of
      accurately capturing the details of the meniscus shape and the viscous losses.
      Furthermore, an effective propagation coefficient was obtained through
      dimensionless analysis that is functionally dependent only on the micropillar
      geometry. The work offers design guidelines to obtain optimal liquid propagation
      rates on micropillar surfaces.

PMID- 20806978
TI  - Orientation and self-assembly of cylindrical particles by anisotropic capillary
      interactions.
AB  - In this research, we study cylindrical microparticles at fluid interfaces.
      Cylinders orient and assemble with high reliability to form end-to-end chains in
      dilute surfaces or dense rectangular lattices in crowded surfaces owing to
      capillary interactions. In isolation, a cylinder assumes one of two possible
      equilibrium states, the end-on state, in which the cylinder axis is perpendicular
      to the interface, or the side-on state, in which the cylinder axis is parallel to
      the interface. A phase diagram relating aspect ratio and contact angle is
      constructed to predict the preferred state and verified in experiment. Cylinders
      in the side-on state create distortions that result in capillary interactions.
      Overlapping deformations by neighboring particles drive oriented capillary
      assembly. Interferometry, electron microscopy, and numerical simulations are used
      to characterize the interface shape around isolated particles. Experiments and
      numerics show that "side-on" cylinders have concentrated excess area near the end
      faces, and that the interface distortion resembles an elliptical quadrupole a few
      radii away from the particle surface. To model the cylinder interactions for
      separations greater than a few radii, an anisotropic potential is derived based
      on elliptical quadrupoles. This potential predicts an attractive force and a
      torque, both of which depend strongly on aspect ratio, in keeping with
      experiment. Particle trajectories and angular orientations recorded by video
      microscopy agree with the predicted potential. In particular, the analysis
      predicts the rate of rotation, a feature lacking in prior analyses. To understand
      interactions near contact, the concentrated excess area near the cylinder ends is
      quantified and its role in creating stable end-to-end assemblies is discussed.
      When a pair of cylinders is near contact, these high excess area regions overlap
      to form a capillary bridge between the particles. This capillary bridge may
      stabilize the end-to-end chains. Finally, on densely packed surfaces, cylinder
      covered colloidosomes form with particles arranged in regular, rectangular
      lattices in the interface; this densely packed structure differs significantly
      from assemblies reported for colloidosomes or particle-stabilized droplets in the
      literature.

PMID- 20806981
TI  - Ion-pair dissociation dynamics of SO(2) in the photon energy range 14.87-15.15
      eV.
AB  - The ion-pair dissociation dynamics of SO(2) -> SO(+) (X(2)Pi,upsilon) + O(-)
      ((2)P(J)) in the excitation energy range 14.87-15.15 eV has been studied using
      the tunable XUV laser and velocity map imaging method. The O(-) yield spectrum,
      the translational energy distributions, and the angular distributions of the
      photofragments have been measured. The electronic structures and selected cuts of
      potential energy surfaces for the ion-pair states have been calculated by
      employing the quantum chemistry calculation method at the CASSCF/6-311++g**
      level. The equilibrium structures of the six ion-pair states all have linear
      geometries. An orbital correlation diagram was drawn to illustrate the ion-pair
      dissociation mechanism. Combining the experimental and theoretical results, it is
      concluded that the ion-pair dissociation takes place mainly via the
      predissociation of Rydberg states (1)A(1) [(C(2)B(1))4db(1)] and (1)A(1)
      [(D(2)A(1))4sa(1)]. The experimental results confirm the previous theoretical
      calculation results about the symmetry assignments for the energy sequence of
      SO(2)(+) as C((2)B(1)) < D((2)A(1)).

PMID- 20806982
TI  - Polytrifluoromethylation versus polyfluorination of the isomers of Kekule benzene
      and phenol: a theoretical study.
AB  - The study of the polyfluorination and polytrifluoromethylation effects on
      electronic structure and intrinsic acidities has been performed using DFT B3LYP
      and NBO calculations for the valence isomers of benzene and phenol, i.e., the
      structures of prismane, benzvalene, Kekule, and Dewar systems. Also the isodesmic
      reaction analysis approach to estimate the effects of the substituents on the
      acidity of the compounds has been used. Although in some systems the additivity
      of fluorine substituents was more than 100%, the acidifying effects of the
      fluorine substituents were comparable to that of the CF(3) in only one case.
      Isodesmic reaction analysis of substituent effects shows that steric effects of
      poly-CF(3) substitution in the alicyclic cage compounds are significantly
      smaller. The relative thermodynamic stabilities of the valence isomers of Kekule
      benzene were significantly lower than that of the aromatic cycle. The
      introduction of fluorine substituents often destabilized the compounds even
      further. Out of the fluorinated hydroxy derivatives of prismane, Dewar benzene,
      and benzvalene, not all are predicted to be stable enough to be able to undergo a
      reversible protonation-deprotonation process. In the case of several hydroxy
      derivatives deprotonation is accompanied by the rupture of a C(alpha)-C(beta)
      bond and in some cases by the rearrangement to the corresponding phenolate anion.
      The isomerization of benzene derivatives resulted in more cases where the
      acidities increased compared with the respective phenol derivatives. The only
      hydroxy compound with significantly higher acidity than the respective phenol was
      pentafluorinated 2-OH-Dewar benzene, which was expected to rival the gas-phase
      acidity of perfluoro-1-adamantanol, currently the most acidic experimentally
      measured perfluorinated alcohol.

PMID- 20806983
TI  - Synthesis and X-ray structure determination of highly active Pd(II), Pd(I), and
      Pd(0) complexes of di(tert-butyl)neopentylphosphine (DTBNpP) in the arylation of
      amines and ketones.
AB  - The air-stable complex Pd(eta(3)-allyl)(DTBNpP)Cl (DTBNpP = di(tert
      butyl)neopentylphosphine) serves as a highly efficient precatalyst for the
      arylation of amines and enolates using aryl bromides and chlorides under mild
      conditions with yields ranging from 74% to 98%. Amination reactions of aryl
      bromides were carried out using 1-2 mol % Pd(eta(3)-allyl)(DTBNpP)Cl at 23-50 
      degrees C without the need to exclude oxygen or moisture. The C-N coupling of the
      aryl chlorides occurred at relatively lower temperature (80-100  degrees C) and
      catalyst loading (1 mol %) using the Pd(eta(3)-allyl)(DTBNpP)Cl precatalyst than
      the catalyst generated in situ from DTBNpP and Pd(2)(dba)(3) (100-140  degrees C,
      2-5 mol % Pd). Other Pd(DTBNpP)(2)-based complexes, (Pd(DTBNpP)(2) and
      Pd(DTBNpP)(2)Cl(2)) were ineffective precatalysts under identical conditions for
      the amination reactions. Both Pd(DTBNpP)(2) and Pd(DTBNpP)(2)Cl(2) precatalysts
      gave nearly quantitative conversions to the product in the alpha-arylation of
      propiophenone with p-chlorotoluene and p-bromoanisole at a substrate/catalyst
      loading of 100/1. At lower substrate/catalyst loading (1000/1), the conversions
      were lower but comparable to that of Pd(t-Bu(3)P)(2). In many cases, the tri-tert
      butylphosphine (TTBP) based Pd(I) dimer, [Pd(MU-Br)(TTBP)](2), stood out to be
      the most reactive catalyst under identical conditions for the enolate arylation.
      Interestingly, the air-stable Pd(I) dimer, Pd(2)(DTBNpP)(2)(MU-Cl)(MU-allyl), was
      less active in comparison to [Pd(MU-Br)(TTBP)](2) and Pd(eta(3)-allyl)(DTBNpP)Cl.
      The X-ray crystal structures of Pd(eta(3)-allyl)(DTBNpP)Cl, Pd(DTBNpP)(2)Cl(2),
      Pd(DTBNpP)(2), and Pd(2)(DTBNpP)(2)(MU-Cl)(MU-allyl) are reported in this paper
      along with initial studies on the catalyst activation of the Pd(eta(3)
      allyl)(DTBNpP)Cl precatalyst.

PMID- 20806984
TI  - Validation of density functional methods for the calculation of small gold
      clusters.
AB  - The performance of various density functional theory methods on the geometries
      and energetics of Au(2), Au(3), Au(4), and Au(5) has been systematically
      evaluated. The results were compared with those from experiments or high-level
      wave function theory methods. In the present study, spin-orbit (SO) coupling was
      considered. It was found that SO coupling plays a very important role in the
      calculation of both the atomization energies and relative stability of the
      isomers of gold clusters. Functionals including SO coupling effect will
      overestimate the atomization energies of gold clusters compared with those just
      including the scalar relativistic (SC) effect. On the other hand, hybrid
      functionals will underestimate the atomization energies compared with those of
      the corresponding pure functionals. For the calculation of the relative stability
      of the different isomers, many functionals not including SO coupling will predict
      the wrong stability order. In addition, SO correction to the atomization energy
      of the cluster (DeltaE(SO)) has a weak dependence on the choice of functional. A
      linear relationship was established between DeltaE(SO) and the number of Au atoms
      and Au-Au bonds in the cluster. The relationship indicates that inclusion of SO
      coupling will favor the isomer with more Au-Au bonds. Among all of the
      functionals evaluated, the SO TPSSh method has the best overall performance, and
      SC M06-L also performs well, although it predicts that the two isomers of Au(3)
      are almost degenerate in energy.

PMID- 20806985
TI  - Role of zinc in the pathogenesis of attention-deficit hyperactivity disorder:
      implications for research and treatment.
AB  - The dopamine transporter is regulated by zinc (Zn2+), which directly interacts
      with the transporter protein as a potent non-competitive blocker of substrate
      translocation (dopamine transport inward and outward). The fact that dysfunction
      of the dopamine transporter is involved in the pathogenesis of attention-deficit
      hyperactivity disorder (ADHD) is interesting in the context of studies that
      suggest the involvement of zinc deficiency in patients with ADHD. In this
      article, we present a hypothesis exploring the causative mechanism of zinc
      deficiency in ADHD and why zinc might be beneficial as a supplementary medication
      and/or adjunct to psychostimulants (methylphenidate, amfetamine) in zinc
      deficient ADHD patients. The hypothesis is based on published in vitro
      observations that the human dopamine transporter contains a high-affinity zinc
      binding site (His-193, His-375, Glu-396) on its extracellular face that modulates
      transporter function, and in vivo studies suggesting that response to stimulants
      is reduced in zinc-deficient ADHD patients. It seems likely that zinc
      supplementation in zinc-deficient ADHD patients improves the binding status of
      insufficiently occupied zinc binding sites on the dopamine transporter. We
      propose to test our hypothesis by recruiting zinc-deficient ADHD patients who
      will undergo positron emission tomography with the 11C-raclopride displacement
      method to investigate whether zinc increases extracellular dopamine levels.

PMID- 20806986
TI  - Management of neuropsychiatric symptoms in people with dementia.
AB  - Neuropsychiatric symptoms are frequent and troublesome in people with dementia
      and present a major treatment challenge for clinicians. Most good practice
      guidelines suggest non-pharmacological treatments as the first-line therapy and
      there is emerging evidence, including randomized controlled trials, that a
      variety of psychological and training interventions, including social interaction
      and person-centred care training, are effective. There is evidence from meta
      analyses that some atypical antipsychotic drugs, specifically risperidone and
      aripiprazole, confer benefit in the treatment of aggression in people with
      Alzheimer's disease over a period of up to 12 weeks. However, these benefits have
      to be considered in the context of significant adverse events, including
      extrapyramidal symptoms, accelerated cognitive decline, stroke and death. In
      addition, the limited evidence available does not indicate ongoing treatment
      benefits over longer periods of therapy. The evidence is limited for other
      pharmacological treatment approaches, but the best evidence is probably for
      carbamazepine, memantine and citalopram. There is very limited evidence for any
      therapies in non-Alzheimer dementias. In conclusion, it is important in most
      situations to limit the use of antipsychotic medication to short-term treatment
      (up to 12 weeks) of severe neuropsychiatric symptoms to limit harm. Non
      pharmacological therapies offer a viable and effective alternative in many
      situations. Adequately powered randomized controlled trials for the treatment of
      clinically significant agitation are urgently needed to explore alternative
      pharmacological therapies.

PMID- 20806988
TI  - Effects of guanfacine extended release on oppositional symptoms in children aged
      6-12 years with attention-deficit hyperactivity disorder and oppositional
      symptoms: a randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of guanfacine extended release
      (XR, Intuniv; Shire Development Inc., Wayne, PA, USA) in the treatment of
      oppositional symptoms in children aged 6-12 years with a diagnosis of attention
      deficit hyperactivity disorder (ADHD) and the presence of oppositional symptoms.
      SUBJECTS AND METHODS: In this randomized, double-blind, placebo-controlled,
      multicentre, flexible-dose, dose-optimization study, children aged 6-12 years
      were randomized to receive guanfacine XR (1-4 mg/day) or placebo for 9 weeks.
      Screening and washout periods were followed by a 5-week dose-optimization period,
      a 3-week dose-maintenance period and a 1-week tapering period. The primary
      efficacy measure was change from baseline to endpoint in the oppositional
      subscale of the Conners' Parent Rating Scale-Revised: Long Form (CPRS-R:L) score.
      Change in ADHD Rating Scale IV (ADHD-RS-IV) total score was a secondary efficacy
      measure. Safety assessments included adverse events (AEs), vital signs, ECG
      readings and laboratory studies. RESULTS: A total of 217 children were enrolled:
      138 were randomized to receive guanfacine XR and 79 to receive placebo. Least
      squares mean reductions from baseline to endpoint in CPRS-R:L oppositional
      subscale scores were 10.9 in the guanfacine XR group compared with 6.8 in the
      placebo group (p < 0.001; effect size = 0.59). A significantly greater reduction
      in ADHD-RS-IV total score from baseline to endpoint was also seen in the
      guanfacine-treated group compared with the placebo group (23.8 vs 11.5,
      respectively; p < 0.001; effect size = 0.92). A post hoc correlation analysis
      between percentage reduction from baseline to endpoint in CPRS-R:L oppositional
      subscale and ADHD-RS-IV total scores indicated that the decreases in oppositional
      symptoms and ADHD symptoms were highly correlated (r = 0.74). The most commonly
      reported, treatment-emergent AEs (TEAEs) in the guanfacine XR group were
      somnolence (50.7%), headache (22.1%), sedation (13.2%), upper abdominal pain
      (11.8%) and fatigue (11.0%) and most were mild or moderate in severity. TEAEs of
      sedation, somnolence or hypersomnia were experienced by 62.5% of subjects in the
      guanfacine XR group. These events were most common during the dose-titration
      period but most (63.5%) resolved prior to the taper period. TEAEs of fatigue,
      lethargy and asthenia were reported in 11.0%, 3.7% and 0.0% of subjects in the
      guanfacine XR group, respectively. Most subjects receiving guanfacine XR
      demonstrated modest changes in blood pressure, pulse rate and ECG readings that
      were not considered clinically significant. CONCLUSIONS: In this population of
      children aged 6-12 years with ADHD and the presence of oppositional symptoms,
      significant reductions in CPRS-R:L oppositional subscale and ADHD-RS-IV total
      scores were observed with guanfacine XR treatment compared with placebo.
      Treatment with guanfacine XR at optimized doses was associated with mostly mild
      or moderate TEAEs. The findings of this study support the efficacy of guanfacine
      XR in the treatment of children with ADHD and the presence of oppositional
      symptoms. CLINICAL TRIAL REGISTRATION NUMBER: NCT00367835.

PMID- 20806989
TI  - Escitalopram: a review of its use in the management of major depressive disorder
      in adults.
AB  - Escitalopram (escitalopram oxalate; Cipralex, Lexapro), a selective serotonin
      reuptake inhibitor (SSRI) indicated for the treatment of major depressive
      disorder (MDD), demonstrates a highly selective and potent, dose-dependent
      inhibition of the human serotonin transporter, inhibiting serotonin reuptake into
      presynaptic nerve terminals and thus increasing serotonergic activity in the CNS.
      With regard to primary endpoints (such as improved scores on the Montgomery
      Asberg Depression Rating Scale [MADRS] and the Hamilton Depression Rating Scale
      [HAM-D]), escitalopram was generally more effective than placebo, at least as
      effective as citalopram, and generally at least as effective as other comparator
      drugs, including the SSRIs fluoxetine, paroxetine and sertraline, the serotonin
      noradrenaline (norepinephrine) reuptake inhibitors (SNRIs) venlafaxine extended
      release and duloxetine, and the aminoketone bupropion in adult patients with MDD
      in short-term, well designed trials. Moreover, it demonstrated a rapid onset of
      antidepressant action. Escitalopram was also found to be cost effective in
      several studies, dominating other SSRIs and venlafaxine extended release.
      Maintenance therapy is commonly required to prevent recurrence of depression.
      Long-term trials corroborated short-term results, with escitalopram demonstrating
      greater efficacy than placebo in relapse prevention. Additionally, escitalopram
      was at least as effective as citalopram, paroxetine and duloxetine in long-term
      comparative trials. Escitalopram has a predictable tolerability profile with
      generally mild to moderate and transient adverse events, and a low propensity for
      drug interactions. Sexual dysfunction with escitalopram treatment appeared to
      occur to a similar or lower extent to that with paroxetine (another SSRI), to a
      similar or greater extent to that with the SNRI duloxetine, and to a greater
      extent than that with the aminoketone bupropion. Thus, escitalopram is an
      effective and generally well tolerated treatment for moderate to severe MDD.
      Escitalopram, like other SSRIs, is an effective first-line option in the
      management of patients with MDD.

PMID- 20806990
TI  - Pharmacoeconomic spotlight on varenicline as an aid to smoking cessation.
AB  - Varenicline (Chantix, Champix) is an orally administered alpha4beta2 nicotinic
      acetylcholine receptor partial agonist that is indicated as an aid to smoking
      cessation. Varenicline was an effective aid to smoking cessation and was
      generally well tolerated in clinical trials, although more data are needed
      regarding the potential for neuropsychiatric events. The costs associated with
      varenicline are offset by direct savings associated with the reduction in smoking
      related diseases. Indeed, despite their limitations, available pharmacoeconomic
      analyses from numerous countries support the use of varenicline for 12 or 24
      weeks as a cost-effective treatment relative to other smoking cessation therapies
      in smokers who wish to quit smoking. For example, in modelled cost-effectiveness
      analyses conducted from a healthcare payer perspective, 12 weeks' treatment with
      varenicline consistently dominated bupropion sustained release and nicotine
      replacement therapy, and was dominant over, or considered cost effective relative
      to, unaided cessation, brief counselling or nortriptyline, with regard to the
      incremental costs per quality-adjusted life-year or life-year gained.

PMID- 20806987
TI  - The association between conventional antidepressants and the metabolic syndrome:
      a review of the evidence and clinical implications.
AB  - Major depressive disorder is a prevalent recurrent medical syndrome associated
      with inter-episodic dysfunction. The metabolic syndrome is comprised of several
      established risk factors for cardiovascular disease (i.e. abdominal obesity,
      dyslipidaemia, dysglycaemia and hypertension). The criterion items of the
      metabolic syndrome collectively represent a multi-dimensional risk factor for
      cardiovascular disease and type 2 diabetes mellitus. Extant evidence indicates
      that both major depressive disorder and the metabolic syndrome, albeit distinct,
      often co-occur and are possibly subserved by overlapping pathophysiology and
      causative mechanisms. Conventional antidepressants exert variable effects on
      constituent elements of the metabolic syndrome, inviting the need for careful
      consideration prior to treatment selection and sequencing. Initiating and
      maintaining antidepressant therapy should include routine surveillance for
      clinical and/or biochemical evidence suggestive of the metabolic syndrome.

PMID- 20806991
TI  - Carotid intima-media thickness: a predictor of response to cholinesterase
      inhibitors in Alzheimer's disease?

PMID- 20806993
TI  - Long-term use of glatiramer acetate by 11 pregnant women with multiple sclerosis:
      a retrospective, multicentre case series.
AB  - BACKGROUND: Glatiramer acetate is a US FDA category B drug with regard to use by
      pregnant women with multiple sclerosis (MS). There are no data currently
      available for the continuous use of glatiramer acetate during pregnancy.
      OBJECTIVE: To assess the risks and benefits of glatiramer acetate used throughout
      pregnancy among women with active MS. DESIGN: Retrospective and multicentre case
      series. SETTINGS: Outpatient services of academic and private institutions caring
      for patients with MS in Brazil. PATIENTS: Eleven women with MS and their children
      were assessed. INTERVENTION: Retrospective evaluation of women with MS who
      received glatiramer acetate continuously for at least 7 months during pregnancy.
      This evaluation was performed by the neurologist responsible for the patient.
      Children aged 1 year and over, born to mothers who received glatiramer acetate
      during pregnancy, were assessed using the Denver II developmental screening test.
      MAIN OUTCOME MEASUREMENTS: Obstetric, neonatal and developmental outcomes.
      RESULTS: No drug-related obstetric complications were observed. No specific drug
      related malformations, neonatal complications or developmental abnormalities were
      observed in the children. Postnatal MS relapse rates remained significantly lower
      than antenatal rates in these patients. CONCLUSIONS: No deleterious effects from
      glatiramer acetate were observed in these pregnant women with MS or in their
      offspring. No increment in postnatal relapse rate was observed. However, the use
      of glatiramer acetate during pregnancy should be restricted to the most difficult
      cases, in which the benefits clearly outweigh the risks.

PMID- 20806994
TI  - Characterization of the UVA protection provided by avobenzone, zinc oxide, and
      titanium dioxide in broad-spectrum sunscreen products.
AB  - BACKGROUND: Solar UV radiation (UVR) is composed of UVB (290-320 nm) and UVA (320
      400 nm) wavelengths. Only two sunscreen active ingredients approved in the US,
      avobenzone (butylmethoxydibenzoylmethane) and zinc oxide (ZnO), provide true
      broad-spectrum protection against UVA wavelengths >360 nm. Although effective
      against shorter UVR wavelengths <360 nm, titanium dioxide (TiO(2)) is also often
      believed to confer broad-spectrum protection and is substituted for ZnO or
      avobenzone. To sustain its absorption capacity within a sunscreen film during UVR
      exposure, avobenzone needs to be formulated into sunscreen products using sound
      formulation strategies. OBJECTIVES: To characterize the efficacy of avobenzone,
      ZnO, and TiO(2) in terms of their abilities to provide broad UVA protection and
      to demonstrate the effectiveness of the different formulation strategies used
      today to maintain the efficacy of avobenzone even during prolonged exposures to
      UVR. METHODS: UVA efficacy was assessed by measuring absorbance profiles in vitro
      using Vitro Skin(r) (IMS Inc., Orange, CT, USA) as an inert substrate and by
      determining UVA protection factors (PFA) on human skin. The impact of avobenzone
      loss on sun protection factor (SPF) and PFA values was evaluated by serially
      reducing avobenzone concentrations in an otherwise photostable product. The
      photostabilizing influence of specific formulation ingredients was monitored by
      measuring the extent to which they prevented UVR-induced degradation of
      avobenzone, whereas photostability of commercial sunscreen products was
      quantified by measuring the percentage change in absorbance within the UVB and
      UVA spectral regions following irradiation of thin product films on inert
      substrates. RESULTS: Model formulations containing 3% avobenzone or 5% ZnO
      provided superior attenuation of UVA wavelengths >360 nm compared with formulas
      containing 5% TiO(2). Additionally, sunscreen products of similar SPF containing
      avobenzone or ZnO exhibited significantly higher PFA values than those containing
      TiO(2). The addition of photostabilized avobenzone or ZnO increased PFA values
      nearly 3-fold, whereas the addition of TiO(2) increased PFA values only modestly.
      Judicious selection of sunscreen actives alone or in combination with extra
      stabilizing agents maintained the photostability of avobenzone in formulations to
      deliver sustained broad-spectrum absorbance during 4 hours of exposure to UVR.
      Small losses (<20%) of avobenzone did not significantly reduce a product's
      protective effects as measured by SPF and PFA values on human skin. CONCLUSIONS:
      TiO(2) provided neither the same level of UVA attenuation nor the same degree of
      UVA protection on human skin as did products containing photostabilized
      avobenzone or ZnO. Hence, TiO(2) cannot be considered a substitute for avobenzone
      or ZnO in providing high levels of UVA protection to human skin. Use of proper
      formulation strategies can ensure that avobenzone losses are minimized to the
      extent that they have no impact on a product's ability to deliver sustained
      protection, even over periods of prolonged exposure to UVR.

PMID- 20806995
TI  - The CDC fourth national report on human exposure to environmental chemicals: what
      it tells us about our toxic burden and how it assist environmental medicine
      physicians.
AB  - The Centers for Disease Control (CDC) conducts ongoing assessments of the levels
      of environmental chemicals in the U.S. population. This ongoing study utilizes
      lab samples from the individuals who are part of the National Health and
      Nutrition Examination Survey (NHANES). The NHANES samples from the years 1999
      2000, 2001-2002, and 2003-2004 (each representing about 2,400 individuals) were
      used for the CDC's national reports. In the CDC Fourth National Report on Human
      Exposure to Environmental Chemicals ("the fourth report") complete data from the
      above sample years were included. Each year additional chemicals are measured;
      the fourth report contains information on 75 previously untested compounds, for a
      total of 212 compounds measured. In the fourth report, blood and urinary levels
      of eight different forms of arsenic are reported. The fourth report, for the
      first time, also includes levels of solvents (30 different compounds) and
      provides adult rather than juvenile values for mercury. In the majority of
      individuals tested, acrylamides, cotinine, trihalomethanes, bisphenol A,
      phthalates, chlorinated pesticides, triclosan, organophosphate pesticides,
      pyrethroids, heavy metals, aromatic hydrocarbons, polybrominated diphenyl ethers,
      benzophenone from sunblock, perfluorocarbons from non-stick coatings, and a host
      of polychlorinated biphenyls and solvents were found. This review provides many
      of the ranges for xenobiotic toxins so a clinician can identify a patient's
      current exposure and toxic load compared to the national averages and monitor the
      effectiveness of prescribed treatments.

PMID- 20806996
TI  - Nutritional treatments for acute myocardial infarction.
AB  - Acute myocardial infarction (MI) is one of the most frequent causes of death in
      the United States. The evaluation and treatment of acute MI in conventional
      medicine has focused primarily on anatomical and physiological factors that lead
      to impaired blood flow. Less attention has been paid to metabolic factors that
      may influence the vulnerability of the myocardium to ischemia and to various
      stressors. There is evidence that in some cases inefficient cellular metabolism,
      rather than the availability of oxygen and other blood-borne nutrients, is an
      important factor determining whether cardiac pathology will develop. Metabolic
      dysfunction could result from intracellular deficiencies of magnesium, coenzyme
      Q10, carnitine, and certain B vitamins, nutrients which play a role in the
      synthesis of adenosine triphosphate (ATP; the body's main storage form of
      energy). In addition, increased oxidative stress may contribute to the
      pathogenesis of both MI-related myocardial damage and reperfusion injury.
      Consequently, administration of antioxidants might improve outcomes in patients
      with acute MI. Numerous clinical trials have found parenteral administration of
      magnesium in the early stages of acute MI can substantially reduce the death
      rate. In addition, several trials have shown L-carnitine is beneficial in the
      treatment of acute MI. Other nutrients, such as vitamin C, vitamin E, and various
      B vitamins, may also be of value.

PMID- 20806997
TI  - Bugs as drugs, Part 1: Insects: the "new" alternative medicine for the 21st
      century?
AB  - Insects and insect-derived products have been widely used in folk healing in many
      parts of the world since ancient times. Promising treatments have at least
      preliminarily been studied experimentally. Maggots and honey have been used to
      heal chronic and post-surgical wounds and have been shown to be comparable to
      conventional dressings in numerous settings. Honey has also been applied to treat
      burns. Honey has been combined with beeswax in the care of several dermatologic
      disorders, including psoriasis, atopic dermatitis, tinea, pityriasis versicolor,
      and diaper dermatitis. Royal jelly has been used to treat postmenopausal
      symptoms. Bee and ant venom have reduced the number of swollen joints in patients
      with rheumatoid arthritis. Propolis, a hive sealant made by bees, has been
      utilized to cure aphthous stomatitis. Cantharidin, a derivative of the bodies of
      blister beetles, has been applied to treat warts and molluscum contagiosum.
      Combining insects with conventional treatments may provide further benefit.

PMID- 20806998
TI  - Randomized controlled trial of electro-acupuncture for autism spectrum disorder.
AB  - OBJECTIVE: To study the efficacy, safety, and compliance of short-term electro
      acupuncture for children with autism spectrum disorder (ASD). DESIGN: Randomized,
      double-blind, sham-controlled, clinical trial. SUBJECTS AND METHODS: Children
      with ASD were randomly assigned to an electro-acupuncture (EA) group (n=30) or a
      sham electro-acupuncture (SEA) group (n=25) matched by age and severity of
      autism. The EA group received electro-acupuncture for selected acupoints while
      the SEA group received sham electro-acupuncture to sham acupoints. A total of 12
      EA and SEA sessions over four weeks were given. Primary outcome measures included
      Functional Independence Measure for Children (WeeFIM), Pediatric Evaluation of
      Disability Inventory (PEDI), Leiter International Performance Scale-Revised
      (Leiter-R), and Clinical Global Impression-Improvement (CGI-I) scale. Secondary
      outcome measures consisted of Aberrant Behavior Checklist (ABC), Ritvo-Freeman
      Real Life Scale (RFRLS), Reynell Developmental Language Scale (RDLS), and a
      standardized parental report. Data were analyzed by the Mann-Whitney test.
      RESULTS: There were significant improvements in the language comprehension domain
      of WeeFIM (p=0.02), self-care caregiver assistant domain of PEDI (p=0.028), and
      CGI-I (p=0.003) in the EA group compared to the SEA group. As for the parental
      report, the EA group also showed significantly better social initiation (p=0.01),
      receptive language (p=0.006), motor skills (p=0.034), coordination (p=0.07), and
      attention span (p=0.003). More than 70 percent of children with ASD adapted to
      acupuncture easily, while eight percent had poor acupuncture compliance. Mild
      side effects of minor superficial bleeding or irritability during acupuncture
      were observed. CONCLUSION: A short, four-week (12 sessions) course of electro
      acupuncture is useful to improve specific functions in children with ASD,
      especially for language comprehension and self-care ability.

PMID- 20806999
TI  - A case of MRSA controlled: predisposing factors and immune stimulation.
AB  - Most treatments for methicillin-resistant Staphylococcus aureus (MRSA) focus on
      agents to eliminate the bacterium. Since MRSA infection is not universal,
      susceptibility factors are possible. Immune resistance could be lowered in such
      individuals; therefore, locating immune-inhibiting or immune-enhancing factors
      might decrease susceptibility. Such seemed to be the case in a 48-year-old female
      who presented with recurring MRSA despite multiple rounds of a variety of
      antibiotics. When the patient encountered an intensely stressful situation an
      outbreak of MRSA occurred. The patient had additional underlying health issues
      that suppressed her immune system and made her more susceptible to stress. Gluten
      allergy and hypothyroidism were discovered and alleviated but did not end the
      MRSA outbreaks. Implementation of a popular treatment from the 1930s, intravenous
      dilute hydrochloric acid (for immune stimulation), prevented most MRSA outbreaks
      when administered frequently. This case provides anecdotal support for the
      proposition that immune enhancement is a viable approach to forestall or clear
      recurring MRSA.

PMID- 20807000
TI  - Resveratrol. Monograph.

PMID- 20807001
TI  - Pterostilbene. Monograph.

PMID- 20807002
TI  - Crataegus oxyacantha (Hawthorn). Monograph.

PMID- 20807003
TI  - Stoic survival: the journey of parenting a premature infant in the bush.
AB  - INTRODUCTION: The birth of a premature infant is a stressful and emotionally
      challenging time for parents. Families living in rural areas often have reduced
      access to the specialist services premature infants require, and different
      concerns from their metropolitan counterparts. Rural families may have to spend
      extended periods of time at a metropolitan centre while their child is in a
      neonatal intensive care unit (NICU). Regular return trips to hospital may be
      required for follow up. Parental experience of this unexpected event and the
      resultant intensive health service involvement requires further examination; most
      studies focus on the NICU experience. This exploratory study was undertaken from
      the rural paediatric allied health perspective. Because there are few accounts of
      rural families' experiences in the literature, this hermeneutic phenomenological
      qualitative study focused on the rural parent's experience of having a premature
      infant in a rural area during the first 12 months of the child's life. METHOD:
      Participants were selectively recruited from the case lists of paediatricians in
      a rural/regional hospital. Seven parents (5 mothers and 2 fathers) of premature
      infants consented to participate in semi-structured interviews. Interviews were
      of 60-90 min duration per parent, and were audiotaped and transcribed verbatim.
      The transcripts were analysed thematically using a phenomenological approach.
      Process and reflection diaries were maintained in order to provide an audit
      trail. RESULTS: The participant group reflected a range of experiences. Parents
      described being initially shocked and then gradually adjusting to being the
      parent of a premature child. Three major themes emerged: (1) 'Coping through
      optimism' when parents consistently spoke positively about even stressful and
      difficult aspects of their experience; (2) 'Stoic survival' where parents did not
      emotionally deal with their experience, often citing others' needs as having
      higher priority; and (3) 'Striving for normal' when parents focussed on the
      aspects of their child's medical care or development that was closer to that of a
      full term child. Parents described feeling devastated if they felt their infant
      regressed or was progressing too slowly, and elated whenever a new milestone was
      achieved. CONCLUSION: Gaining insight into the experience of parents of premature
      infants can help health professionals ensure services more effectively meet the
      needs of these families. Rural families were pleased with their local services
      although they indicated that travelling to a metropolitan centre was extremely
      burdensome. While the families interviewed had access to some local specialist
      services, they expressed concern that if they resided in a more remote area there
      would be reduced access to services and greater personal strain. Further research
      is required to determine the experiences of Indigenous families, separated or
      divorced parents and families living in remote areas.

PMID- 20807004
TI  - Silver nanoparticle impregnated poly (E-caprolactone) scaffolds: optimization of
      antimicrobial and noncytotoxic concentrations.
AB  - Use of silver nanoparticles (SNPs) for control of implant-associated infection is
      a promising strategy, if optimum antimicrobial yet nontoxic dose to mammalian
      cells is identified. This study was done to determine essential quantity of SNPs,
      which stimulate antimicrobial activity without cytotoxicity, when immobilized on
      poly (E-caprolactone) (PCL) scaffold proposed for vascular tissue engineering.
      During SNP synthesis and scaffold preparation, nanoparticle aggregation was
      protected using poly (ethylene glycol). Transmission electron microscopy was used
      to characterize SNP size and to detect its mobilization from scaffold to culture
      medium. Antimicrobial property of the SNP and its dose response was tested using
      both Gram-positive and Gram-negative bacteria by zone of inhibition assay.
      Endothelial cells (ECs), the main cell type required for vascular tissue
      engineering, were grown on scaffolds to identify the nontoxic dose. After seeding
      EC on scaffolds, cell attachment, spreading, and viability/survival were detected
      using specific markers by flow cytometric/fluorescence microscopic analysis. Real
      time polymerase chain reaction detected effect of SNPs on mRNA expression of
      selected EC-specific functional proteins. Results suggest that even devoid of
      antibiotics in the medium, 0.1% (w/w) SNP on PCL scaffold is antimicrobial while
      nontoxic to EC at cellular and molecular level once cultured on the SNP-PCL
      scaffold.

PMID- 20807005
TI  - Dynamic culturing of smooth muscle cells in tubular poly(trimethylene carbonate)
      scaffolds for vascular tissue engineering.
AB  - Porous, tubular, flexible, and elastic poly(trimethylene carbonate) (PTMC)
      scaffolds (length 8 cm and inner diameter 3 mm) for vascular tissue engineering
      were prepared by means of a dip-coating and particulate leaching procedure. Using
      NaCl as porogen, scaffolds with an average pore size of 110 MUm and a porosity of
      85% were obtained. Before leaching the salt, the structures were made creep
      resistant by means of crosslinking at 25 kGy gamma irradiation. To increase the
      efficiency of cell seeding, the scaffolds were provided with a microporous outer
      layer of 0.2 mm with an average pore size of 28 MUm and a porosity of 65% (total
      wall thickness 1 mm). Human smooth muscle cells (SMCs) were seeded in these
      scaffolds with an efficiency of 43%, as determined after 24 h cell adhesion. SMCs
      were cultured in the scaffolds up to 14 days under stationary conditions or under
      pulsatile flow conditions in a bioreactor (pressure 70-130 mmHg, 69
      pulsations/min, and average wall shear rate 320 s(-1)). Although SMCs
      proliferated under both conditions, cell numbers were three to five times higher
      in case of dynamic culturing. This was qualitatively confirmed by means of
      histology. Also, in terms of mechanical properties, the dynamically cultured
      constructs performed better than the statically cultured constructs. After
      culturing for 14 days, the maximum tensile strengths of the constructs,
      determined in the radial direction, had increased from 0.16 MPa (unseeded
      scaffold) to 0.48 MPa (dynamic culturing) and 0.38 MPa (static culturing). The
      results of this study indicate that a potentially useful medial layer for tissue
      engineered vascular grafts can be prepared by dynamic culturing of human SMCs
      seeded in porous tubular poly(trimethylene carbonate) scaffolds.

PMID- 20807006
TI  - Varying regional topology within knee articular chondrocytes under simulated in
      vivo conditions.
AB  - Topographical cartilage variation across the knee joint has been previously
      reported, but there is only limited information on such gene expression profiles.
      Articular chondrocytes from eight different topographical regions of bovine knee
      joints were seeded within three-dimensional scaffolds and further cultured under
      static conditions (unloaded control group) or subjected to an artificial joint
      environment within a bioreactor (loaded group). Constructs were analyzed for
      glycosaminoglycan (GAG), DNA, and expression of Collagen-1,-2,-10, Aggrecan,
      COMP, Sox9, PRG-4, PTHrp, and MMP-1,-3,-13 mRNA after 2 weeks of in vitro
      culture. Exclusively among loaded constructs the overall GAG production was
      significantly different between regions. Patella chondrocytes had overall
      highest, and cells from the femoral notch had overall lowest GAG/DNA under loaded
      conditions. Gene expression was significantly different between regions for all
      targets except for Sox9, PRG-4, and PTHrp among controls and with the exception
      of Aggrecan, Sox9, and PTHrp among loaded samples. Under mechanical stimulation
      Collagen-1,-2 and Aggrecan was highest at the patello-femoral joint, whereas it
      was lowest at typical cartilage biopsy regions. There is a clear topographical
      variation among distinct regions across the knee joint for gene and matrix
      expression profiles under static and foremost under dynamic conditions.

PMID- 20807007
TI  - Late motherhood and cesarean delivery.

PMID- 20807008
TI  - Oxygen and oxidative stress in bronchopulmonary dysplasia.
AB  - AIMS: to summarize present knowledge regarding the relation between oxidative
      stress and development of bronchopulmonary dysplasia (BPD). METHODS: relevant
      literature searched at Pubmed and other sources. RESULTS: Oxidative stress is
      generated in a number of conditions and by a number of causes such as
      inflammation and hyperoxia. Ontogenic aspects are discussed. Oxidative stress as
      physiological regulators, its relation to transcription factors and inflammation
      is summarized. The role of oxygen and antioxidant therapy and newborn
      resuscitation for development and prevention of BPD as well as new therapeutic
      modes especially the use of growth factors, gene therapy and stem cells, are
      briefly discussed. CONCLUSION: oxidative stress and BPD are associated. A better
      understanding of this association is necessary in order to reduce the severity
      and the incidence of the condition.

PMID- 20807009
TI  - Ethical dimensions of periviability.
AB  - The birth of neonates at the limits of viability, or periviability, poses
      numerous challenges to health care providers and to systems of care, and the care
      of these pregnancies and neonates is fraught with ethical controversies. This
      statement summarizes the ethical principles involved in the care of periviable
      pregnancies and neonates, and provides expert clinical opinion about the numerous
      challenges posed by this problem around the world. Topics addressed include a
      summary of the published experience, an ethical framework, translating neonatal
      outcome data to the obstetric arena, management as a trial of intervention,
      referral to tertiary centers, neonatal resuscitation, cesarean delivery for fetal
      indication, and limits on life-sustaining neonatal treatment.

PMID- 20807010
TI  - Genome profiles in maternal blood during early onset preeclampsia and towards
      term.
AB  - AIMS: inflammatory processes are present during preeclampsia and in normal
      pregnancy. Maternal inflammatory reactions may change towards term. Our objective
      was to evaluate genome signaling in blood during preeclampsia and towards term
      using microarrays. METHODS: RNA microarrays (Illumina) were conducted on blood
      from preeclamptic pregnancies delivered preterm, normal pregnancies at term and
      normal pregnancies at gestational week 31. Two statistical methods (Q-value cut
      off 1%) identified data structures in the three groups and retrieved activated
      genes along a time axis and a diseased-healthy axis. Signaling genes were
      localized within known pathways and gene sets, and genes associated with
      inflammation were identified. RESULTS: early onset preeclampsia and term
      pregnancies both showed distinct expression patterns when compared to normal
      pregnancy at gestational week 31. In preeclampsia, 19 genes were differentially
      expressed, including a down-regulation of CC-chemokine receptor 3 (CCR3). Among
      the 183 differentially expressed genes towards term, tumor necrosis factor
      superfamily member 15 (TNFSF15) was up-regulated and interferon-gamma receptor 2
      (IFNGR2) and CXC-chemokine receptor type 4 (CXCR4) were down-regulated. Seven of
      the genes were similarly changed during preeclampsia and towards term.
      CONCLUSIONS: a possible type 1 immune response was identified both during
      preeclampsia and towards term. In pre-eclampsia a premature activation of
      leucocytes might be present.

PMID- 20807011
TI  - Long chain polyunsaturated fatty acids in mothers of preterm babies.
AB  - AIMS: to examine the levels of docosahexaenoic acid (DHA) and arachidonic acid
      (AA) in both plasma and erythrocytes of maternal and cord blood as well as in
      breast milk of mothers of preterm babies. METHODS: a total of 63 mothers of
      preterm babies were recruited from the Bharati Medical Hospital, Pune, India.
      RESULTS: plasma and erythrocyte DHA and AA levels were higher (P<0.001) in cord
      blood than in maternal blood. Maternal plasma DHA and AA were positively (P<0.01)
      associated with their respective maternal erythrocyte levels. There was a
      positive association (P<0.01) between maternal DHA (both plasma and erythrocyte)
      and cord DHA. Maternal plasma omega 3 and 6 fatty acids were positively (P<0.01)
      associated with their respective milk fatty acids. CONCLUSIONS: higher DHA and AA
      levels in cord blood compared to the mothers suggests a special mechanism to meet
      the increased demand of the fetus. Higher levels of milk DHA reflect the
      increased postnatal requirement of preterm babies suggesting a vital role for
      maternal milk. Lower maternal erythrocyte DHA concentrations in mothers
      delivering preterm as compared to term suggest that increased oxidative stress
      may be responsible for reduced DHA levels. This may alter the uterotonic factors
      like prostaglandins leading to premature triggering of labor.

PMID- 20807013
TI  - Proliferation of human keratinocytes and cocultured human keratinocytes and
      fibroblasts in three-dimensional fibrin constructs.
AB  - Over the last several years, our in vitro and in vivo studies have focused on
      optimizing the use of fibrin to deliver cells. We have shown that some three
      dimensional (3D) fibrin constructs with specific fibrinogen and thrombin
      concentration support robust proliferation of normal human dermal fibroblasts,
      whereas different fibrinogen and thrombin concentrations support high mesenchymal
      stem cell proliferation in 3D fibrin constructs. In this article, we found that
      normal human epithelial keratinocytes proliferate well in 3D fibrin constructs
      consist of fibrinogen concentration ranging from 17 to 33 mg/mL and thrombin
      concentration of 1 U/mL. Further, using a new proliferation assay, we studied the
      proliferation of fibroblasts and keratinocytes cocultured in various 3D fibrin
      constructs of different fibrinogen and thrombin concentrations. We found that 3D
      fibrin constructs with a range of fibrinogen concentration (5-34 mg/mL) and a
      thrombin concentration of 1 U/mL produce an optimal cell proliferation for both
      cell types when cocultured. This profile of proliferation is different from that
      seen when keratinocytes or fibroblasts are incorporated separately in 3D fibrin
      constructs. In conclusion, we found that one needs to choose the fibrinogen and
      thrombin concentration carefully depending on the cell type to deliver; that is,
      different fibrin constructs with different fibrinogen and thrombin concentration
      are required to deliver fibroblasts or keratinocytes alone or to codeliver both
      cell types. Moreover, there seems to be a cross-talk between keratinocytes and
      fibroblasts when they are cointroduced in 3D fibrin constructs. This feedback
      could be due to the effects of growth factors produced by the two cell types in
      the 3D fibrin constructs.

PMID- 20807012
TI  - Teriparatide therapy and beta-tricalcium phosphate enhance scaffold
      reconstruction of mouse femoral defects.
AB  - To investigate the efficacy of endocrine parathyroid hormone treatment on tissue
      engineered bone regeneration, massive femoral defects in C57Bl/6 mice were
      reconstructed with either 100:0 or 85:15 poly-lactic acid (PLA)/beta-tricalcium
      phosphate (beta-TCP) scaffolds (hereafter PLA or PLA/betaTCP, respectively),
      which were fabricated with low porosity (<30%) to improve their structural
      rigidity. Experimental mice were treated starting at 1 week postop with daily
      subcutaneous injections of 40 MUg/kg teriparatide until sacrifice at 9 weeks,
      whereas control mice underwent the same procedure but were injected with sterile
      saline. Bone regeneration was assessed longitudinally using planar X-ray and
      quantitative microcomputed tomography, and the reconstructed femurs were
      evaluated at 9 weeks either histologically or biomechanically to determine their
      torsional strength and rigidity. Teriparatide treatment increased bone volume and
      bone mineral content significantly at 6 weeks and led to enhanced trabeculated
      bone callus formation that appeared to surround and integrate with the scaffold,
      thereby establishing union by bridging bone regeneration across the segmental
      defect in 30% of the reconstructed femurs, regardless of the scaffold type.
      However, the bone volume and mineral content in the PLA reconstructed femurs
      treated with teriparatide was reduced at 9 weeks to control levels, but remained
      significantly increased in the PLA/betaTCP scaffolds. Further, bridged
      teriparatide-treated femurs demonstrated a prototypical brittle bone torsion
      behavior, and were significantly stronger and stiffer than control specimens or
      treated specimens that failed to form bridging bone union. Taken together, these
      observations suggest that intermittent, systemic parathyroid hormone treatment
      can enhance bone regeneration in scaffold-reconstructed femoral defects, which
      can be further enhanced by mineralized (betaTCP) particles within the scaffold.

PMID- 20807014
TI  - Enhanced rat islet function and survival in vitro using a biomimetic self
      assembled nanomatrix gel.
AB  - Peptide amphiphile (PA) is a peptide-based biomaterial that can self-assemble
      into a nanostructured gel-like scaffold, mimicking the chemical and biological
      complexity of natural extracellular matrix. To evaluate the capacity of the PA
      scaffold to improve islet function and survival in vitro, rat islets were
      cultured in three different groups--(1) bare group: isolated rat islets cultured
      in a 12-well nontissue culture-treated plate; (2) insert group: isolated rat
      islets cultured in modified insert chambers; (3) nanomatrix group: isolated rat
      islets encapsulated within the PA nanomatrix gel and cultured in modified insert
      chambers. Over 14 days, both the bare and insert groups showed a marked decrease
      in insulin secretion, whereas the nanomatrix group maintained glucose-stimulated
      insulin secretion. Moreover, entire islets in the nanomatrix gel stained positive
      for dithizone up to 14 days, indicating better maintained glucose-stimulated
      insulin production. Fluorescein diacetate/propidium iodide staining results also
      verified necrosis in the bare and insert groups after 7 days, whereas the PA
      nanomatrix gel maintained islet viability after 14 days. Thus, these results
      demonstrate the potential of PAs as an intermediary scaffold for increasing the
      efficacy of pancreatic islet transplantation.

PMID- 20807016
TI  - Ossifying bone marrow explant culture as a three-dimensional mechanoresponsive in
      vitro model of osteogenesis.
AB  - Mechanical cues play an important role in bone regeneration and affect production
      and secretion dynamics of growth factors (GFs) involved in osteogenesis. The in
      vitro models for investigating the mechanoresponsiveness of the involvement of
      GFs in osteogenesis are limited to two-dimensional monolayer cell culture
      studies, which do not effectively embody the physiological interactions with the
      neighboring cells of different types and the interactions with a natural
      extracellular matrix. Natural bone formation is a complex process that
      necessitates the contribution of multiple cell types, physical and chemical cues
      in a three-dimensional (3D) setting. There is a need for in vitro models that
      represent the physiological diversity and characteristics of bone formation to
      realistically study the effects of mechanical cues on this process. In vitro
      cultures of marrow explants inherently ossify and they embody the multicellular
      and 3D nature of osteogenesis. Therefore, the aim of this study was to assess the
      mechanoresponsiveness of the scaffold-free, multicellular, and 3D model of
      osteogenesis based on inherent marrow ossification and to investigate the effects
      of mechanical loading on the osteoinductive GF production dynamics of this model.
      These aims were achieved by (1) culturing rat bone marrow explants for 28 days
      under basal conditions that facilitate inherent ossification, (2) employing
      mechanical stimulation (compressive loading) between days 12 and 26, and (3)
      quantifying the final ossified volume (OV) and the production levels of bone
      morphogenetic protein-2, vascular endothelial growth factor, insulin-like growth
      factor-1, and transforming growth factor-beta1. The results showed that the final
      OV of the marrow explants increased by about fourfold in mechanically stimulated
      samples. Further, mechanical stimulation sustained the production level of
      vascular endothelial growth factor (starting day 21), which otherwise declined
      temporally under static conditions. The production levels of insulin-like growth
      factor-1 and transforming growth factor-beta1 were enhanced under the effect of
      loading after day 21. In addition, significant correlations were observed between
      the final OV and the levels of GFs analyzed. In conclusion, this study
      demonstrates that the scaffold-free, multicellular, and 3D model of bone
      formation based on inherent ossification of marrow tissue is mechanoresponsive
      and mechanical loading improves in vitro osteogenesis in this model with
      sustaining or enhancing osteoinductive GF production levels, which otherwise
      would decline with increasing time.

PMID- 20807015
TI  - Magnetic resonance studies of macromolecular content in engineered cartilage
      treated with pulsed low-intensity ultrasound.
AB  - Noninvasive monitoring of matrix development in tissue-engineered cartilage
      constructs would permit ongoing assessment with the ability to modify culture
      conditions during development to optimize tissue characteristics. In this study,
      chondrocytes seeded in a collagen hydrogel were exposed for 20 min/day to pulsed
      low-intensity ultrasound (PLIUS) at 30 mWcm(-2) and cultured for up to 5 weeks.
      Biochemical assays, histology, immunohistochemistry, Fourier transform infrared
      spectroscopy, and magnetic resonance imaging (MRI) were performed at weeks 3 and
      5 after initiation of growth. The noninvasive MRI measurements were correlated
      with those from the invasive studies. In particular, MRI transverse relaxation
      time (T2) and magnetization transfer rate (k(m)) correlated with macromolecular
      content, which was increased by application of PLIUS. This indicates the
      sensitivity of MR techniques to PLIUS-induced changes in matrix development, and
      highlights the potential for noninvasive assessment of the efficacy of anabolic
      interventions for engineered tissue.

PMID- 20807017
TI  - Elastic properties of induced pluripotent stem cells.
AB  - The recent technique of transducing key transcription factors into unipotent
      cells (fibroblasts) to generate pluripotent stem cells (induced pluripotent stem
      cells [iPSCs]) has significantly changed the stem cell field. These cells have
      great promise for many clinical applications, including that of regenerative
      medicine. Our findings show that iPSCs can be derived from human adipose-derived
      stromal cells (hASCs), a notable advancement in the clinical applicability of
      these cells. To investigate differences between two iPS cell lines (fibroblast
      iPSC and hASC-iPSC), and also the gold standard human embryonic stem cell, we
      looked at cell stiffness as a possible indicator of cell differentiation
      potential differences. We used atomic force microscopy as a tool to determine
      stem cell stiffness, and hence differences in material properties between cells.
      Human fibroblast and hASC stiffness was also ascertained for comparison.
      Interestingly, cells exhibited a noticeable difference in stiffness. From least
      to most stiff, the order of cell stiffness was as follows: hASC-iPSC, human
      embryonic stem cell, fibroblast-iPSC, fibroblasts, and, lastly, as the stiffest
      cell, hASC. In comparing hASC-iPSCs to their origin cell, the hASC, the
      reprogrammed cell is significantly less stiff, indicating that greater
      differentiation potentials may correlate with a lower cellular modulus. The
      stiffness differences are not dependent on cell culture density; hence, material
      differences between cells cannot be attributed solely to cell-cell constraints.
      The change in mechanical properties of the cells in response to reprogramming
      offers insight into how the cell interacts with its environment and might lend
      clues to how to efficiently reprogram cell populations as well as how to maintain
      their pluripotent state.

PMID- 20807018
TI  - Image-guided transnasal endoscopic techniques in the management of orbital
      disease.
AB  - PURPOSE: To assess the utility of image-guided transnasal endoscopic surgery for
      a variety of orbital diseases requiring decompression of at least one orbital
      wall. METHOD: A descriptive case series of consecutive orbital procedures
      requiring decompression of at least one wall. All procedures were performed using
      a transnasal endoscopic approach and an intraoperative image-guided LandmarX
      system for anatomical guidance. RESULTS: A 3-year review yielded 17 cases,
      including 6 cases with compressive mucoceles, 4 neoplasms, 4 patients with
      proptosis secondary to Graves' Ophthalmopathy, 1 case of an intraorbital abscess,
      1 fungal mycetoma, and 1 hemangioma. These cases all had improved postoperative
      clinical status without any serious complications. The LandmarX system was a
      valuable intraoperative tool in all 17 cases. CONCLUSIONS: The endoscopic
      transnasal approach to orbital decompression surgery allows for good
      visualization and is minimally invasive. Using this approach in conjunction with
      the LandmarX image-guided system allows for improved anatomical localization and
      provided good results in all cases.

PMID- 20807019
TI  - Reversal of experimental diabetes in mice by transplantation of neo-islets
      generated from human amnion-derived mesenchymal stromal cells using immuno
      isolatory macrocapsules.
AB  - BACKGROUND AIMS: The ethical and biologic limitations with current sources of
      stem cells have resulted in a quest to look for alternative sources of
      multipotent stem cells of human origin. Amniotic membrane is of interest as a
      source of cells for regenerative medicine because of its ease of availability,
      plasticity and inexhaustible source that does not violate the sanctity of
      independent life. Although researchers have shown the stem cell-like potential of
      human amniotic epithelial cells, the mesenchymal part of amnion has remained less
      explored. METHODS: We established a long-term culture of mesenchymal-like stem
      cells derived from full-term human amniotic membrane and their differentiation
      into functional pancreatic lineage. RESULTS: The amnion-derived mesenchymal-like
      stem cells expressed various mesenchymal markers and demonstrated multilineage
      differentiation capacity. We also observed that these cells could form islet-like
      clusters (ILC) on exposure to serum-free defined media containing specific growth
      factor and differentiating agents. Differentiated ILC showed expression of human
      insulin, glucagon and somatostatin by immunocytochemistry, while quantitative
      reverse transcription/real-time-polymerase chain reaction (qRT-PCR) data
      demonstrated the expression of insulin, glucagon, somatostatin, Ngn3 and Isl1.
      Moreover, encapsulation of the ILC in polyurethane-polyvinyl pyrrolidone
      macrocapsules and their subsequent transplantation in experimental diabetic mice
      resulted in restoration of normoglycemia, indicating their ability to respond to
      high glucose without immunorejection. CONCLUSIONS: Our results demonstrate that
      amnion-derived mesenchymal stromal cells can undergo islet neogenesis, indicating
      amnion as an alternative source of islets for cell replacement therapy in
      diabetes.

PMID- 20807021
TI  - Improved proliferation and differentiation capacity of human mesenchymal stromal
      cells cultured with basement-membrane extracellular matrix proteins.
AB  - BACKGROUND AIMS: In vitro cultured mesenchymal stromal cells (MSC) are
      characterized by a short proliferative lifespan, an increasing loss of
      proliferation capacity and progressive reduction of differentiation potential.
      Laminin-1, laminin-5, collagen IV and fibronectin are important constituents of
      the basement membrane extracellular matrix (ECM) that are involved in a variety
      of cellular activities, including cell attachment and motility. METHODS AND
      RESULTS: The in vitro proliferation capacity of MSC was significantly improved
      when the cells were incubated in the presence of basement membrane ECM proteins.
      For example, a mixture of proteins improved proliferation capacity 250-fold in
      comparison with standard conditions after five passages. Furthermore, in colony
      forming unit-fibroblast (CFU-F) assays colony numbers and size were significantly
      extended. Blocking specific integrin cell-surface receptors, positive effects on
      the proliferation capacity of MSC were inhibited. Additionally, when MSC were co
      cultivated with ECM proteins, cells maintained their multipotential
      differentiation capacity throughout many culture passages in comparison with
      cells cultivated on plastic. However, expansion of MSC on laminin-5 suppressed
      any subsequent chondrogenic differentiation. CONCLUSIONS: Our results suggest
      that expansion of bone marrow-derived MSC in the presence of ECM proteins is a
      powerful approach for generating large numbers of MSC, showing a prolonged
      capacity to differentiate into mesodermal cell lineages, with the exception of
      the lack of chondrogenesis by using laminin-5 coating.

PMID- 20807020
TI  - Mesenchymal stromal cells from donors varying widely in age are of equal cellular
      fitness after in vitro expansion under hypoxic conditions.
AB  - BACKGROUND AIMS: Mesenchymal stromal cells (MSC) are gaining in popularity as an
      experimental therapy for a number of conditions that often require expansion ex
      vivo prior to use. Data comparing clinical-grade MSC from various ages of donors
      are scant. We hypothesized that MSC from older donors may display differences in
      cellular fitness when expanded for clinical use. METHODS: We evaluated the
      expression of several markers of aging, oxidative stress and growth kinetics, and
      telomere length, in MSC obtained from a wide age range (8 months to 58 years).
      RESULTS: To evaluate cellular fitness we compared MSC expanded from younger (8
      months-6 years) versus older (38-58 years) donors in terms of selected cell
      surface markers, lipofuscin, migration ability, telomere length and expression of
      iNOS, PGE2, p16INK and SOD. Results did not differ between these groups. Neither
      SOD activity (0.025 versus 0.028 U/mL) nor death after oxidative challenge was
      significantly different (1% versus 1.5%, P = 0.14). We did find that, although
      MSC from older individuals produced slightly fewer cells over a 28-day culture
      period and had a slightly longer doubling time (54 h versus 42 hr, a satisfactory
      clinical product could still be obtained regardless of age cohort. CONCLUSIONS:
      Collectively, these data show that MSC can be expanded without significant
      alterations in expansile properties or obvious changes in parameters associated
      with senescence. Because cellular fitness was equivalent in these cohorts, MSC
      from donors up to age 58 years can be used as a source of cells for cellular
      therapy.

PMID- 20807022
TI  - Rotavirus gastroenteritis in Finnish children in 2006-2008, at the introduction
      of rotavirus vaccination.
AB  - Rotaviruses (RV) are major causative agents of acute gastroenteritis (AGE)
      requiring hospitalization in children; RV hospitalizations may be largely
      eliminated by universal mass vaccination with RV vaccine. We conducted a hospital
      based prospective survey of AGE in children over 2 RV epidemic seasons, from 2006
      to 2008, when the coverage of RV vaccination in Finland increased to 35% of the
      birth cohort. RVs were detected by reverse transcription polymerase chain
      reaction (RT-PCR). In the first season, only 38% of AGE cases were RV-positive,
      and the onset of the RV season was delayed. Type G1P[8], RVs accounted for 40%,
      G2P[4] for 19%, G3P[8] for 2%, G4P[8] for 2% and G9P[8] for 38%. In the second
      season, 63% of AGE cases were RV-positive: G1P[8] accounted for 73%, G2P[4] for
      only 3%, G3P[8] for 4%, G4P[8] for 13%, and G9P[8] had almost disappeared. G2P[4]
      RV did not become predominant at the coverage level of 29% of G1P[8] human RV
      vaccine. RV-associated hospitalizations were seen in children up to the age of 9
      y. This study forms the epidemiological background for the follow-up of the
      impact of universal RV vaccination in Finland introduced in 2009.

PMID- 20807023
TI  - Posterior semicircular canal dehiscence in asymptomatic ears.
AB  - CONCLUSIONS: This study revealed that, in the adult population, the final
      diagnosis of this entity can only be made by combining imaging with clinical
      tests. OBJECTIVE: We developed the largest temporal bone multislice computed
      tomography (CT) scan study so far by including 410 cases to investigate the
      prevalence of posterior semicircular canal dehiscence in patients with symptoms
      unrelated to the inner ear. METHODS: A prospective study was performed in 410
      consecutive adult individuals who underwent temporal bone multislice CT scan
      examinations. RESULTS: The prevalence of posterior semicircular canal dehiscence
      was determined to be 1.2%. No superior or lateral semicircular canal defect was
      detected in these five patients. All cases with posterior semicircular canal
      defect were male. In two cases the canal was located unilaterally, while in three
      cases the defects were present bilaterally. Otological examination and
      audiovestibular tests revealed no abnormal findings in any of the individuals.

PMID- 20807024
TI  - News from the Biological Stain Commission No. 10.
AB  - In the 10th issue of News from the Biological Stain Commission (BSC), under the
      heading of Regulatory affairs, the Biological Stain Commission's International
      Affairs Committee presents information from the meeting of ISO/TC 212/WG 1 held
      in London, UK, on 16-17 November 2009. Furthermore, the items ISO CEN Vienna
      Agreement and CEN Annex Z are explained in more detail.

PMID- 20807025
TI  - The antifungal activity of human parotid secretion is species-specific.
AB  - Candida albicans is the major fungal colonizer of the oral cavity and causes oral
      candidiasis in immunocompromised patient populations. While antifungal proteins
      in saliva have been identified and the virulence factors of C. albicans have been
      well studied, little is known about the role saliva plays in the preferential
      colonization of the oral cavity by C. albicans. We report that the fungistatic
      activity of human parotid secretion toward six C. albicans strains is
      considerably lower than towards nine non-C. albicans fungal species (average IC50
      values >1000 mg/l and <70 mg/l, respectively). The species-specific activity of
      parotid secretion suggests that saliva may play a determining role in oral fungal
      colonization patterns.

PMID- 20807026
TI  - Endophthalmitis caused by Phialophora verrucosa and Streptococcus intermedius: a
      case report.
AB  - The most common pathogenic germs of mycotic endophthalmitis are Candida, Fusarium
      and Aspergillus fumigatus. As a dematiaceous fungus, Phialophora verrucosa
      (Medlar, 1915) has not been reported to cause endophthalmitis. Herein, we report
      a case of endophthalmitis induced by P. verrucosa and Streptococcus intermedius.

PMID- 20807027
TI  - Gut colonization by Candida albicans aggravates inflammation in the gut and extra
      gut tissues in mice.
AB  - We examined whether Candida albicans gut colonization aggravates immune diseases
      in mice. Chronic and latent C. albicans gut colonization was established by the
      intragastric inoculation of C. albicans in mice fed as part of a purified diet.
      Allergic diarrhea was induced by repetitive intragastric administration of
      ovalbumin in sensitized BALB/c mice. Contact hypersensitivity was evaluated by
      measuring ear swelling after topical application of 2, 4-dinitrofluorobenzene in
      NC/Nga mice. Arthritis was induced by intradermal injection of bovine type-II
      collagen emulsified with complete Freund's adjuvant in DBA/1J mice. C. albicans
      gut colonization increased the incidence of allergic diarrhea, which was
      accompanied by gut hyperpermeability, as well as increased infiltration of
      inflammatory cells in the colon. Contact hypersensitivity was also exacerbated by
      C. albicans gut colonization, as demonstrated by increased swelling,
      myeloperoxidase activity, and proinflammatory cytokines in ear auricles.
      Furthermore, C. albicans gut colonization promoted limb joint inflammation in
      collagen-induced arthritis, in an animal model of rheumatoid arthritis. These
      findings suggest that C. albicans gut colonization in mice aggravates
      inflammation in allergic and autoimmune diseases, not only in the gut but also in
      the extra-gut tissues and underscores the necessity of investigating the
      pathogenic role of C. albicans gut colonization in immune diseases in humans.

PMID- 20807028
TI  - Bloodstream yeast infections in a university hospital in Northeast Turkey: a 4
      year survey.
AB  - This study presents data on species distribution and antifungal susceptibility
      profiles of Candida bloodstream isolates obtained from a Turkish Tertiary Care
      Hospital during a 4-year period. All hospitalized patients who had >= 1 blood
      culture positive for yeast during their hospital stay from January 2005 through
      2009 were included in this study. All isolates were identified to species level
      using CHROMagar and ID 32 C. Fluconazole and voriconazole antifungal
      susceptibility testing was performed using the disk diffusion method according to
      CLSI M44-A. In vitro activity of amphotericin B was determined by the Etest. Of
      all 166 yeast isolates, C. albicans was the dominant species (34.3%), followed by
      Candida parapsilosis (28.9%) and C. tropicalis (8.4%). All of the 48 C.
      parapsilosis strains were identified as C. parapsilosis sensu stricto. Resistance
      to fluconazole was more common among C. krusei isolates. Voriconazole resistance
      was absent. One C. lusitaniae strain showed a high amphotericin MIC (4 MUg/ml).
      Our survey indicated an increase of some non-C. albicans Candida species in our
      hospital while antifungal resistance was uncommon.

PMID- 20807029
TI  - Immunohistochemical and ultra-structural detection of Pneumocystis in wild boars
      (Sus scrofa) co-infected with porcine circovirus type 2 (PCV2) in Southern
      Brazil.
AB  - Pneumocystis spp. are fungi that are able to infect a variety of host species
      and, occasionally, lead to severe pneumonia. Porcine circovirus type 2 (PCV2) is
      an important viral pathogen which affects both swine and wild boar herds
      worldwide. Co-infection between PCV2 and other pathogens has been reported, and
      the secondary immunodeficiency caused by the virus may predispose to these co
      infections. In the present study, postmortem tissue samples obtained from wild
      boar herds in Southern Brazil were analyzed by histopathology, ultra-structural
      observation, and immunohistochemistry. Forty-seven out of seventy-eight (60%)
      wild boars showed clinical signs, gross, and histopathological lesions
      characteristic of infection by PCV2. Pneumocystis was detected by
      immunohistochemistry in 39 (50%) lungs and viral antigens of PCV2 were found in
      29 (37.2%) samples. Concomitant presence of Pneumocystis and PCV2 were observed
      in 16 (20.5%) of the wild boars. Cystic and trophic forms of Pneumocystis were
      similar to previously described ultra-structural observations in other mammals.

PMID- 20807030
TI  - Mold colonization of fiberglass insulation of the air distribution system:
      effects on patients with hematological malignancies.
AB  - We investigated mold colonization of air handling units (AHUs) of heating,
      ventilating, and air conditioning (HVAC) systems and its effects, including
      invasive pulmonary mycoses and febrile neutropenia, in patients with
      hematological malignancies. Sample collection with transparent adhesive tape and
      culture swabs revealed that AHUs were heavily colonized with molds, including
      thermotolerant, variously distributed Penicillium spp. Cases of nosocomial
      invasive pulmonary mycosis were not clustered in specific patient rooms but did
      occur frequently when the HVAC systems were not in use, prior to intervention
      (i.e., sealing and disuse of AHUs in private room), and during construction of a
      new hospital building. Multivariate logistic regression analysis of initial
      episodes of febrile neutropenia showed that the rate of febrile neutropenia was
      significantly associated with the duration of neutropenia (odds ratio [OR]: 1.16;
      95% confidence interval [CI]: 1.07-1.27) and with sex (OR: 0.469; CI: 0.239
      0.902). An evaluation of private rooms showed that female patients also had a
      lower rate of fever after intervention (OR: 0.0016; 95% CI: 0.000-0.209). The
      reduced rate of febrile neutropenia after intervention suggests that mold
      colonization of AHUs had adverse effects on patients with hematological
      malignancies.

PMID- 20807031
TI  - Differential transcriptional profiles induced by amphotericin B formulations on
      human monocytes during response to hyphae of Aspergillus fumigatus.
AB  - Amphotericin B formulations possess diverse immunomodulatory properties that may
      contribute to the activity of phagocytes against invasive aspergillosis. In this
      work we provide a novel set of data on different gene transcriptional profiles of
      monocytes exposed to the combination of Aspergillus fumigatus and amphotericin B
      formulations. We used pathway-specific microarray analysis, RT-PCR analysis and
      enzyme-linked immunosorbent assays to compare the effects of amphotericin B
      deoxycholate (DAMB) at 1 MUg/ml and amphotericin B lipid complex (ABLC) at 5
      MUg/ml to assess gene expression of immune molecules of THP-1 cells exposed to A.
      fumigatus hyphae (AF) for 4 h. A. fumigatus hyphae at effector/target ratio 10/1
      induced mostly chemotactic factors for monocyte recruitment. DAMB at 1 MUg/ml in
      the presence or absence of AF induced the most pronounced changes in pro
      inflammatory and chemokine gene expression, while ABLC under the same conditions
      caused less dramatic effect. There was a reciprocal response of increased
      expression of the genes encoding IL-1beta and IL-20 and decreased expression of
      IL-10, IL-2 and IL-3 in response of monocytes to both the hyphae and antifungal
      agents. These results demonstrate that amphotericin B formulations exert
      differential effects on genes encoding pro-inflammatory molecules,
      immunoregulatory molecules and chemokines by human monocytes during response to
      A. fumigatus and that these molecules may affect antifungal activity.

PMID- 20807033
TI  - The concept of collaborative health.
AB  - Based on empirical research about teamwork in human service organizations in
      Sweden, the concept of collaborative health (CH) encapsulates the physical,
      psychological and social health resources the individual uses in teamwork;
      resources which at the same time are influenced by the teamwork. My argument
      built on empirical research leading up to identifying and defining the core
      concept in this article, is that teamwork affects team members' health and this
      in turn affects the teamwork and its outcome. In this paper collaborative health
      is viewed from a social constructionism perspective and discussed in relation to
      earlier concepts developed in social psychology and working life research,
      including psychosocial stress and burnout. The paper also introduces the concept
      of functional synergy, which in this context is defined as the simultaneous
      presence of sharp goal-orientation and synergy in teamwork. The need for a
      holistic team theory is emphasized as a tool in research on teamwork. Such a
      theory relies on identifying sound and illuminating constituent concepts. I
      suggest that collaborative health could be a useful concept for better
      understanding the complex collaborative and co-operative teamwork of human
      service organizations of today.

PMID- 20807032
TI  - Respiratory tract allergic disease and atopy: experimental evidence for a fungal
      infectious etiology.
AB  - Allergic asthma is an obstructive lung disease linked to environmental exposures
      that elicit allergic airway inflammation and characteristic antigen-specific
      immunoglobulin reactions termed atopy. Analyses of asthma pathogenesis using
      experimental models have shown that T helper cells, especially T helper type 2
      (Th2) cells and Th2 cytokines such as interleukin 4 (IL-4) and IL-13, are
      critical mediators of airway obstruction following allergen challenge, but the
      environmental initiators of lung Th2 responses are less defined. Our studies
      demonstrate that fungal-derived proteinases that are commonly found in home
      environments are requisite immune adjuvants capable of eliciting robust Th2
      responses and allergic lung disease in mice. We have further shown that common
      household fungi readily infect the mouse respiratory tract and induce both asthma
      like disease and atopy to otherwise innocuous bystander antigens through the
      secretion of proteinases. These findings support the possibility that asthma and
      atopy represent a reaction to respiratory tract fungal infection, suggesting
      novel means for diagnosis and therapy of diverse allergic disorders.

PMID- 20807034
TI  - Nurse-physician collaboration in an acute care community hospital.
AB  - Despite the evidence from the literature of the benefits of collaboration, a
      collaborative practice model in the acute-care setting remains the exception
      rather than the dominant practice. The purpose of this study was to evaluate
      attitudes toward collaboration among nurses and physicians practicing in an acute
      care community hospital. The sample included 118 nurses and 53 physicians.
      Background variables of gender, age, education, experience, practice setting,
      cultural background, and time to interact were examined to determine if they
      influenced attitudes towards collaboration. The results indicated that both
      physicians and nurses expressed positive attitudes towards collaboration but that
      there was a significant difference on two of the underlying factors: shared
      education and physician authority. The study may serve as a baseline for future
      research, specifically focused on interventions to enhance collaboration.

PMID- 20807035
TI  - Risk Factors and Outcomes for Vancomycin-Resistant Enterococcus Bloodstream
      Infection in Children.
AB  - Background and objective. Enterococcal bloodstream infections (BSIs) cause
      morbidity and mortality in children. This study aims to describe the
      epidemiological characteristics of enterococcal BSI, to determine the risk
      factors for vancomycin-resistant Enterococcus (VRE) BSI, and to compare outcomes
      of VRE BSI and vancomycin-susceptible Enterococcus (VSE) BSI in this population.
      Methods. A retrospective cohort study at a 418-bed tertiary care children's
      hospital in Philadelphia, Pennsylvania, examined the epidemiological
      characteristics of children hospitalized with enterococcal BSI during the period
      from 2001 through 2006. A nested case-control study compared patients with VRE
      BSI with control patients with VSE BSI. Analysis included regression modeling to
      identify independent risk factors for VRE BSI. Results. We identified 339
      patients with enterococcal BSI during the study period, including 39 patients
      with VRE infection. Fifty-three patients (16%) died before hospital discharge.
      Risk factors for VRE included long-term receipt of mechanical ventilation
      (adjusted odds ratio [OR], 5.40 [95% confidence interval {CI}, 1.28-6.48]),
      receipt of immunosuppressive medications during the preceding 30 days (adjusted
      OR, 2.88 [95% CI, 1.40-20.78]), use of vancomycin during the 2 weeks before onset
      of bacteremia (adjusted OR per day of vancomycin use, 1.25 [95% CI, 1.14-1.38]),
      and older age (adjusted OR, 1.08 [95% CI, 1.03-1.14]). VRE BSI was not associated
      with an increased length of stay after onset of bacteremia (0.77 days [95% CI,
      0.55-1.07 days]). Mortality was higher for VRE BSI, but the difference was not
      statistically significant (adjusted OR, 1.94 [95% CI, 0.78-4.8]). Conclusion.
      Most enterococcal BSI in children was caused by VSE. Risk factors for VRE BSI
      included receipt of vancomycin, long-term receipt of mechanical ventilation,
      immunosuppression, and older age. Differences in length of stay and mortality
      were not detected.

PMID- 20807036
TI  - Comparing quantitative culture of a blood sample obtained through the catheter
      with differential time to positivity in establishing a diagnosis of catheter
      related bloodstream infection.

PMID- 20807037
TI  - Revised SHEA position paper: influenza vaccination of healthcare personnel.

PMID- 20807038
TI  - A quick whole-mount staining protocol for bone deposition and resorption.
AB  - Osteoblasts and osteoclasts, two cell types important in bone development, are
      associated with enzymes capable of hydrolyzing phosphate groups. These enzymes
      are important for their function of bone deposition and resorption. Alkaline
      phosphatase (AP) activity is associated with the cell surface of osteoblasts,
      while osteoclasts secrete tartrate-resistant acid phosphatase (TRAP). Due to
      their shared enzymatic properties, we were able to develop a simple whole-mount
      staining protocol to stain for both enzymes (TRAP and AP) within the same
      teleostean tissue sample. In addition, we were able to perform each reaction
      individually. Further, AP and TRAP stains were maintained through
      decalcification, embedding, and sectioning procedures. Staining can also be
      conducted after sectioning depending on the question under investigation. These
      rapid staining protocols can thus be used to observe the processes involved in
      bone remodeling in whole teleost specimens, and/or the location of the stain can
      be determined through sectioning. The ability to observe bone deposition and
      resorption in such a capacity will significantly advance our understanding of
      bone remodeling throughout the life history of organisms and also within
      particular skeletal elements.

PMID- 20807039
TI  - Combined use of MS-222 (tricaine) and isoflurane extends anesthesia time and
      minimizes cardiac rhythm side effects in adult zebrafish.
AB  - As an important vertebrate model organism, zebrafish are typically studied at the
      embryonic stage to take advantage of their properties of transparency and rapid
      development. However, more and more studies require assays to be done on adults.
      Consequently, a good anesthetic is needed to sedate and immobilize the adult
      zebrafish during experimental manipulation. To date, MS-222 (tricaine
      methanesulfonate) is the only Food and Drug Administration approved anesthetic
      for aquaculture and is widely used by the zebrafish research community.
      Nevertheless, in adult zebrafish, MS-222 reduces heart rate and causes high
      mortality under long-term sedation. Consequently, adult zebrafish have limited
      research applications. In this study, we present a new anesthetic formula for the
      adult zebrafish that results in minimal side effects on its physiology under
      prolonged sedation. The combined use of MS-222 with isoflurane effectively
      extended the time of anesthesia, and the zebrafish recovered faster than when
      anesthetized with the traditional MS-222. Moreover, MS-222 + isoflurane did not
      cause reduction of heart rates, which enabled long-term electrocardiogram
      recording and microscopic observation on the adult zebrafish. Taken together, the
      new MS-222 + isoflurane formula will facilitate general applications of adult
      zebrafish in time-consuming experiments with minimal side effects on the model
      organism's overall physiology.

PMID- 20807041
TI  - Thank you, no.

PMID- 20807042
TI  - Just say no to the use of no: alternative terminology for improving anatomic
      pathology reports.
AB  - Several organizations have recently suggested several approaches to make medicine
      safer, including defining "never events." To date, never events have not been
      defined in anatomic pathology. We recently had a case in which the word "no" was
      left off the final diagnosis; as a result the diagnosis both made sense and was
      the exact opposite of what was intended. We therefore wondered if using the word
      "no" or "not" in the final diagnosis should be never events in pathology. We
      reviewed all amendments from the past 5 years and identified a total of 8 cases
      (0.5% of all amendments) where the words no or not were left out of the final
      diagnosis. One author (A.A.R.) attempted to avoid the words no and not in the
      final diagnosis during a 4-month period by using alternative words such as
      negative, benign, and unremarkable. If these words were left out, the resulting
      diagnosis no longer made sense. The use of no and not was reduced from 9.3% of
      all cases to 0.4% of all cases (P < .001). We suggest that using the words no and
      not are dangerous in the final diagnosis and should be classified as never events
      in anatomic pathology.

PMID- 20807043
TI  - A new study of intraosseous blood for laboratory analysis.
AB  - CONTEXT: Intraosseous (IO) blood is frequently used to establish a blood
      chemistry profile in critically ill patients. Questions remain regarding the
      reliability of IO blood for laboratory analysis and established criteria
      regarding the amount of marrow/blood to waste before taking an IO sample are not
      available. OBJECTIVES: To evaluate IO-derived blood for routine laboratory blood
      tests needed in the care of critically ill patients and to determine the amount
      of marrow/blood to waste before drawing blood from the IO space for laboratory
      analysis. DESIGN: Blood samples were drawn from peripheral veins of 10
      volunteers. Within 5 minutes, 2 IO blood samples were obtained; one following 2
      mL of waste and another following 6 mL of waste. Samples were analyzed for
      complete blood count and chemistry profile. Values were analyzed using Pearson
      correlation coefficients. Levels of significance were determined using the t
      distribution. Mean values for the draws were calculated and compared, with the
      intravenous blood sample serving as a control for the IO samples. RESULTS: There
      was a significant correlation between intravenous and IO samples for red blood
      cell counts and hemoglobin and hematocrit levels but not for white blood cell
      counts and platelet counts. There was a significant correlation between
      intravenous and IO samples for glucose, blood urea nitrogen, creatinine,
      chloride, total protein, and albumin concentrations but not for sodium,
      potassium, CO(2), and calcium levels. CONCLUSIONS: When venous blood cannot be
      accessed, IO blood aspirate may serve as a reliable alternate, especially for
      hemoglobin and hematocrit levels and most analytes in a basic blood chemistry
      profile. Exceptions are CO(2) levels and platelet counts, which may be lower, and
      white blood cell counts, which may appear elevated.

PMID- 20807044
TI  - Acute erythroid leukemia.
AB  - CONTEXT: Acute erythroid leukemia (AEL) is an uncommon type of acute myeloid
      leukemia (AML), representing less than 5% of all cases. Acute erythroid leukemia
      is characterized by a predominant erythroid proliferation, and in the current
      World Health Organization (WHO) classification scheme there are 2 subtypes:
      erythroleukemia (erythroid/myeloid leukemia) and pure erythroid leukemia.
      Morphologic findings are most important for establishing the diagnosis. The
      erythroleukemia subtype, which is most common, is defined as the presence of 50%
      or more erythroid precursors and 20% or more blasts in the nonerythroid
      component. The pure erythroid leukemia subtype is composed of 80% or more
      immature erythroblasts. Although these morphologic criteria appear
      straightforward, AEL overlaps with other types of AML and myelodysplastic
      syndrome that are erythroid rich. OBJECTIVE: To provide an update of AEL,
      including clinical presentation, morphologic features, immunophenotype, and
      cytogenetic and molecular data. As the erythroleukemia subtype is most common,
      the literature and this review are biased towards this subtype of AEL. DATA
      SOURCES: Clinicopathologic, cytogenetic, and molecular information were extracted
      from our review of pertinent literature and a subset of AEL cases in the files of
      The University of Texas M. D. Anderson Cancer Center (Houston) and University of
      South Alabama (Mobile). CONCLUSIONS: The current WHO criteria for establishing
      the diagnosis of AEL reduce the frequency of this entity, as cases once
      classified as the erythroleukemia subtype are now reclassified as other types of
      AML, particularly AML with myelodysplasia-related changes and therapy-related
      AML. This reclassification also may have prognostic significance for patients
      with the erythroleukemia subtype of AEL. In contrast, the current WHO criteria
      appear to have little impact on the frequency and poor prognosis of patients with
      the pure erythroid leukemia subtype of AEL. Molecular studies, preferably using
      high-throughput methods, are needed for a better understanding of the
      pathogenesis of AEL, and for developing diagnostic and prognostic markers.

PMID- 20807045
TI  - Adenocarcinoma in ectopic prostatic tissue at dome of bladder: a case report of a
      patient with urothelial carcinoma of the bladder and adenocarcinoma of the
      prostate.
AB  - We report a case of ectopic prostate tissue with an associated prostatic
      adenocarcinoma occurring in the dome of the urinary bladder. A 62-year-old man
      presented with a 4-month history of persistent microscopic hematuria following a
      urinary tract infection. Other complaints included frequent urination, but there
      was neither dysuria nor gross hematuria. Digital rectal examination revealed a
      smooth prostate of normal size. Cystoscopic examination revealed a sessile lesion
      of the anterior bladder neck and multiple smaller papillary lesions throughout
      the bladder. Following a transurethral resection of the bladder tumor with a
      diagnosis of muscle-invasive transitional cell carcinoma grade 3, a radical
      cystoprostatectomy was performed. The diagnosis of transitional cell carcinoma
      was confirmed, but in addition, a different lesion was also incidentally found in
      the dome of the bladder. This incidental lesion showed a prostatic adenocarcinoma
      arising from ectopic prostatic tissue within the bladder submucosa. The prostate
      also showed prostatic adenocarcinoma, but this was minimal, low grade, and
      confined to the prostate gland, and thus it was felt to be unlikely to have
      metastasized to the bladder dome. Adenocarcinoma arising in ectopic prostatic
      tissue is a rare finding and to our knowledge only 1 case has been previously
      described, occurring in the soft tissue adjacent to the prostate. We report the
      first case of adenocarcinoma arising in ectopic prostatic tissue within the
      bladder.

PMID- 20807046
TI  - MicroRNAs in benign and malignant hematopoiesis.
AB  - MicroRNAs (miRNAs) are a family of 19- to 24-nucleotide noncoding RNAs that
      regulate messenger RNA function at the posttranscriptional and translational
      level. Recent literature demonstrates a significant role of miRNAs in normal and
      malignant hematopoiesis. Specific miRNAs have been shown to regulate each step of
      hematopoiesis starting at the level of multipotent progenitors through terminal
      stages of myeloid and lymphoid differentiation. Similarly, individual miRNAs and
      miRNA signatures have been associated with specific hematologic malignancies.
      There is accumulating evidence that miRNAs can be used for diagnostic,
      prognostic, and therapeutic purposes. This review highlights the current status
      of knowledge on miRNA in normal and malignant hematopoiesis.

PMID- 20807050
TI  - Cross-modal processing in the occipito-temporal cortex: a TMS study of the Muller
      Lyer illusion.
AB  - The Muller-Lyer illusion occurs both in vision and in touch, and transfers cross
      modally from vision to haptics [Mancini, F., Bricolo, E., & Vallar, G.
      Multisensory integration in the Muller-Lyer illusion: From vision to haptics.
      Quarterly Journal of Experimental Psychology, 63, 818-830, 2010]. Recent evidence
      suggests that the neural underpinnings of the Muller-Lyer illusion in the visual
      modality involve the bilateral lateral occipital complex (LOC) and right superior
      parietal cortex (SPC). Conversely, the neural correlates of the haptic and cross
      modal illusions have never been investigated previously. Here we used repetitive
      TMS (rTMS) to address the causal role of the regions activated by the visual
      illusion in the generation of the visual, haptic, and cross-modal visuo-haptic
      illusory effects, investigating putative modality-specific versus cross-modal
      underlying processes. rTMS was administered to the right and the left hemisphere,
      over occipito-temporal cortex or SPC. rTMS over left and right occipito-temporal
      cortex impaired both unisensory (visual, haptic) and cross-modal processing of
      the illusion in a similar fashion. Conversely, rTMS interference over left and
      right SPC did not affect the illusion in any modality. These results demonstrate
      the causal involvement of bilateral occipito-temporal cortex in the
      representation of the visual, haptic, and cross-modal Muller-Lyer illusion, in
      favor of the hypothesis of shared underlying processes. This indicates that
      occipito-temporal cortex plays a cross-modal role in perception both of illusory
      and nonillusory shapes.

PMID- 20807051
TI  - Spatial perspective and coordinate systems in autoscopy: a case report of a
      "fantome de profil" in occipital brain damage.
AB  - Autoscopic phenomena refer to complex experiences involving the illusory
      reduplication of one's own body. Here we report the third long-lasting case of
      autoscopy in a patient with right occipital lesion. Instead of the commonly
      reported frontal mirror view (fantome speculaire), the patient saw her head and
      upper trunk laterally in side view (fantome de profil). We found that the visual
      appearance and completeness of the autoscopic image could be selectively
      modulated by active and passive movements, without being influenced by imagining
      the same movements or by tactile and auditory stimulation. Eyes closure did not
      disrupt either the perception of the autoscopic body or the effects of the motor
      stimulation. Moreover, the visual body reduplication was coded neither in purely
      eye-centered nor in head-centered frames of reference, suggesting the involvement
      of egocentric coordinate systems (eyes and head centered). A follow-up
      examination highlighted the stability of the visual characteristics of the body
      reduplication and its shift induced by displacement of both head and eyes. These
      findings support the view that autoscopic phenomena have a multisensory motor
      origin and proprioceptive signals may play an important role in modulating the
      illusory visual reduplication of the patient's own body, most likely via cross
      modal modulation of extrastriate areas involved in body and face perception.

PMID- 20807052
TI  - Dietary restraint violations influence reward responses in nucleus accumbens and
      amygdala.
AB  - Numerous studies have demonstrated that consuming high-calorie food leads to
      subsequent overeating by chronic dieters. The present study investigates the
      neural correlates of such self-regulatory failures using fMRI. Chronic dieters (n
      = 50) and non-dieters (n = 50) consumed either a 15-oz glass of cold water or a
      15-oz milkshake and were subsequently imaged while viewing pictures of animals,
      environmental scenes, people, and appetizing food items. Results revealed a
      functional dissociation in nucleus accumbens and amygdala activity that
      paralleled well-established behavioral patterns of eating observed in dieters and
      non-dieters. Whereas non-dieters showed the greatest nucleus accumbens activity
      in response to food items after water consumption, dieters showed the greatest
      activity after consuming the milkshake. Activity in the left amygdala
      demonstrated the reverse interaction. Considered together with previously
      reported behavioral findings, the present results offer a suggested neural
      substrate for diet failure.

PMID- 20807054
TI  - Active ignoring in early visual cortex.
AB  - Selective attention is critical for controlling the input to mental processes.
      Attentional mechanisms act not only to select relevant stimuli but also to
      exclude irrelevant stimuli. There is evidence that we can actively ignore
      irrelevant information. We measured neural activity relating to successfully
      ignoring distracters (using preview search) and found increases in both the
      precuneus and primary visual cortex during preparation to ignore distracters. We
      also found reductions in activity in fronto-parietal regions while previewing
      distracters and a reduction in activity in early visual cortex during search when
      a subset of items was successfully excluded from search, both associated with
      precuneus activity. These results are consistent with the proposal that actively
      excluding distractions has two components: an initial stage where distracters are
      encoded, and a subsequent stage where further processing of these items is
      inhibited. Our findings suggest that it is the precuneus that controls this
      process and can modulate activity in visual cortex as early as V1.

PMID- 20807053
TI  - The involvement of occipital and inferior frontal cortex in the phonological
      learning of Chinese characters.
AB  - Neural changes related to the learning of the pronunciation of Chinese characters
      in English speakers were examined using fMRI. We examined the item-specific
      learning effects for trained characters and the generalization of phonetic
      knowledge to novel transfer characters that shared a phonetic radical (part of a
      character that gives a clue to the whole character's pronunciation) with trained
      characters. Behavioral results showed that shared phonetic information improved
      performance for transfer characters. Neuroimaging results for trained characters
      over learning found increased activation in the right lingual gyrus, and greater
      activation enhancement in the left inferior frontal gyrus (Brodmann's area 44)
      was correlated with higher accuracy improvement. Moreover, greater activation for
      transfer characters in these two regions at the late stage of training was
      correlated with better knowledge of the phonetic radical in a delayed recall
      test. The current study suggests that the right lingual gyrus and the left
      inferior frontal gyrus are crucial for the learning of Chinese characters and the
      generalization of that knowledge to novel characters. Left inferior frontal gyrus
      is likely involved in phonological segmentation, whereas right lingual gyrus may
      subserve processing visual-orthographic information.

PMID- 20807055
TI  - Brain areas consistently linked to individual differences in perceptual decision
      making in younger as well as older adults before and after training.
AB  - Perceptual decision-making performance depends on several cognitive and neural
      processes. Here, we fit Ratcliff's diffusion model to accuracy data and reaction
      time distributions from one numerical and one verbal two-choice perceptual
      decision task to deconstruct these performance measures into the rate of evidence
      accumulation (i.e., drift rate), response criterion setting (i.e., boundary
      separation), and peripheral aspects of performance (i.e., nondecision time).
      These theoretical processes are then related to individual differences in brain
      activation by means of multiple regression. The sample consisted of 24 younger
      and 15 older adults performing the task in fMRI before and after 100 daily 1-hr
      behavioral training sessions in a multitude of cognitive tasks. Results showed
      that individual differences in boundary separation were related to striatal
      activity, whereas differences in drift rate were related to activity in the
      inferior parietal lobe. These associations were not significantly modified by
      adult age or perceptual expertise. We conclude that the striatum is involved in
      regulating response thresholds, whereas the inferior parietal lobe might
      represent decision-making evidence related to letters and numbers.

PMID- 20807056
TI  - Can the language-dominant hemisphere be predicted by brain anatomy?
AB  - It has long been suspected that cortical interhemispheric asymmetries may
      underlie hemispheric language dominance (HLD). To test this hypothesis, we
      determined interhemispheric asymmetries using stereology and MRI of three
      cortical regions hypothesized to be related to HLD (Broca's area, planum
      temporale, and insula) in healthy adults in whom HLD was determined using
      functional transcranial Doppler sonography and functional MRI (15 left HLD, 10
      right HLD). We observed no relationship between volume asymmetry of the gyral
      correlates of Broca's area or planum temporale and HLD. However, we observed a
      robust relationship between volume asymmetry of the insula and HLD (p = .008),
      which predicted unilateral HLD in 88% individuals (86.7% left HDL and 90% right
      HLD). There was also a subtle but significant positive correlation between the
      extent of HLD and insula volume asymmetry (p = .02), indicating that a larger
      insula predicted functional lateralization to the same hemispheric side for the
      majority of subjects. We found no visual evidence of basic anatomical markers of
      HLD other than that the termination of the right posterior sylvian fissure was
      more likely to be vertical than horizontal in right HLD subjects (p = .02).
      Predicting HLD by virtue of gross brain anatomy is complicated by interindividual
      variability in sulcal contours, and the possibility remains that morphological
      and cytoarchitectural organization of the classical language regions may underlie
      HLD when analyses are not constrained by the natural limits imposed by
      measurement of gyral volume. Although the anatomical correlates of HLD will most
      likely be found to include complex intra- and interhemispheric connections, there
      is the possibility that such connectivity may correlate with gray matter
      morphology. We suggest that the potential significance of insular morphology
      should be considered in future studies addressing the anatomical correlates of
      human language lateralization.

PMID- 20807057
TI  - Sustained preferential processing of social threat cues: bias without
      competition?
AB  - Stimuli of high emotional significance such as social threat cues are
      preferentially processed in the human brain. However, there is an ongoing debate
      whether or not these stimuli capture attention automatically and weaken the
      processing of concurrent stimuli in the visual field. This study examined
      continuous fluctuations of electrocortical facilitation during competition of two
      spatially separated facial expressions in high and low socially anxious
      individuals. Two facial expressions were flickered for 3000 msec at different
      frequencies (14 and 17.5 Hz) to separate the electrocortical signals evoked by
      the competing stimuli ("frequency tagging"). Angry faces compared to happy and
      neutral expressions were associated with greater electrocortical facilitation
      over visual areas only in the high socially anxious individuals. This finding was
      independent of the respective competing stimulus. Heightened electrocortical
      engagement in socially anxious participants was present in the first second of
      stimulus viewing and was sustained for the entire presentation period. These
      results, based on a continuous measure of attentional resource allocation,
      support the view that stimuli of high personal significance are associated with
      early and sustained prioritized sensory processing. These cues, however, do not
      interfere with the electrocortical processing of a spatially separated concurrent
      face, suggesting that they are effective at capturing attention, but are weak
      competitors for resources.

PMID- 20807058
TI  - Voluntary explicit versus involuntary conceptual memory are associated with
      dissociable fMRI responses in hippocampus, amygdala, and parietal cortex for
      emotional and neutral word pairs.
AB  - Although functional neuroimaging studies have supported the distinction between
      explicit and implicit forms of memory, few have matched explicit and implicit
      tests closely, and most of these tested perceptual rather than conceptual
      implicit memory. We compared event-related fMRI responses during an intentional
      test, in which a group of participants used a cue word to recall its associate
      from a prior study phase, with those in an incidental test, in which a different
      group of participants used the same cue to produce the first associate that came
      to mind. Both semantic relative to phonemic processing at study, and emotional
      relative to neutral word pairs, increased target completions in the intentional
      test, but not in the incidental test, suggesting that behavioral performance in
      the incidental test was not contaminated by voluntary explicit retrieval. We
      isolated the neural correlates of successful retrieval by contrasting fMRI
      responses to studied versus unstudied cues for which the equivalent "target"
      associate was produced. By comparing the difference in this repetition-related
      contrast across the intentional and incidental tests, we could identify the
      correlates of voluntary explicit retrieval. This contrast revealed increased
      bilateral hippocampal responses in the intentional test, but decreased
      hippocampal responses in the incidental test. A similar pattern in the bilateral
      amygdale was further modulated by the emotionality of the word pairs, although
      surprisingly only in the incidental test. Parietal regions, however, showed
      increased repetition-related responses in both tests. These results suggest that
      the neural correlates of successful voluntary explicit memory differ in
      directionality, even if not in location, from the neural correlates of successful
      involuntary implicit (or explicit) memory, even when the incidental test taps
      conceptual processes.

PMID- 20807059
TI  - Dynamic norm-based encoding for unfamiliar shapes in human visual cortex.
AB  - Previous studies have argued that faces and other objects are encoded in terms of
      their deviation from a class prototype or norm. This prototype is associated with
      a smaller neural population response compared with nonprototype objects. However,
      it is still unclear (1) whether a norm-based representation can emerge for
      unfamiliar or novel object classes through visual experience at the time scale of
      an experiment and (2) whether the results from previous studies are caused by the
      prototypicality of a stimulus, by the physical properties of individual stimuli
      independent from the stimulus distribution, and/or by the trial-to-trial
      adaptation. Here we show with a combined behavioral and event-related fMRI study
      in humans that a short amount of visual experience with exemplars from novel
      object classes determines which stimulus is represented as the norm.
      Prototypicality effects were observed at the behavioral level by behavioral
      asymmetries during a stimulus comparison task. The fMRI data revealed that class
      exemplars closest to the prototypes--the perceived average of each class--were
      associated with a smaller response in the anterior part of the visual object
      selective cortex compared with other class exemplars. By dissociating between the
      physical characteristics and the prototypicality status of the stimuli and by
      controlling for trial-to-trial adaptation, we can firmly conclude for the first
      time that high-level visual areas represent the identity of exemplars using a
      dynamic, norm-based encoding principle.

PMID- 20807060
TI  - Representation of action in occipito-temporal cortex.
AB  - A fundamental question for social cognitive neuroscience is how and where in the
      brain the identities and actions of others are represented. Here we present a
      replication and extension of a study by Kable and Chatterjee [Kable, J. W., &
      Chatterjee, A. Specificity of action representations in the lateral occipito
      temporal cortex. Journal of Cognitive Neuroscience, 18, 1498-1517, 2006]
      examining the role of occipito-temporal cortex in these processes. We presented
      full-cue movies of actors performing whole-body actions and used fMRI to test for
      action- and identity-specific adaptation effects. We examined a series of
      functionally defined regions, including the extrastriate and fusiform body areas,
      the fusiform face area, the parahippocampal place area, the lateral occipital
      complex, the right posterior superior temporal sulcus, and motion-selective area
      hMT+. These regions were analyzed with both standard univariate measures as well
      as multivoxel pattern analyses. Additionally, we performed whole-brain tests for
      significant adaptation effects. We found significant action-specific adaptation
      in many areas, but no evidence for identity-specific adaptation. We argue that
      this finding could be explained by differences in the familiarity of the stimuli
      presented: The actions shown were familiar but the actors performing the actions
      were unfamiliar. However, in contrast to previous findings, we found that the
      action adaptation effect could not be conclusively tied to specific functionally
      defined regions. Instead, our results suggest that the adaptation to previously
      seen actions across identities is a widespread effect, evident across lateral and
      ventral occipito-temporal cortex.

PMID- 20807061
TI  - Obsessive-compulsive disorder and Tourette's disorder: where are we now?

PMID- 20807063
TI  - An overview of the treatment of Tourette's disorder and tics.
AB  - OBJECTIVE: The aim of this study was to review the efficacy of various treatments
      for Tourette's disorder (TD) and tics. METHOD: This study is a historical review
      of the treatment modalities prior to the advent of neuroleptics. A review of
      double-blind and placebo-controlled clinical trials and open studies on the use
      of neuroleptics and selected reports was also carried out. RESULTS: The
      literature review reveals that the treatment of TD and tics has evolved from an
      early history of marginally effective approaches to the advent of neuroleptics,
      which started a new era in TD and tic treatment, with a significantly broader
      range of effectiveness. CONCLUSIONS: Although progress has been made, the
      literature review nevertheless reveals a great deal of confusion as related to
      the clinical heterogeneity of TD and tics, differences in populations, medication
      dose combinations, and outcomes. However, a role for a limited number of
      pharmacologic agents, combined with psychosocial approaches, has been identified.
      There is a need for studies in larger, diagnostically homogenous samples and for
      the use of more sophisticated methodology, to identify intelligible models that
      would allow the development of more effective treatment approaches.

PMID- 20807064
TI  - Tic suppression: the medical model.
AB  - Tics are intermittent, repetitive, patterned but usually nonrhythmic motor
      movements or sounds performed in response to urges or involuntarily. They are the
      cardinal symptom required for a DSM-IV-TR diagnosis of Tourette's disorder (TD).
      Many children with TD present with mild tics that cause no significant
      impairment. However, when tics cause pain or interference, medical treatment is
      reasonable. This article reviews current evidence for treatment of tics in TD
      with medications as well as deep brain stimulation and transcranial magnetic
      stimulation. It concludes with some context for understanding this literature,
      relevant to treatment decisions and future treatment research in TD.

PMID- 20807062
TI  - Neurobiological substrates of Tourette's disorder.
AB  - OBJECTIVE: This article reviews the available scientific literature concerning
      the neurobiological substrates of Tourette's disorder (TD). METHODS: The
      electronic databases of PubMed, ScienceDirect, and PsycINFO were searched for
      relevant studies using relevant search terms. RESULTS: Neuropathological as well
      as structural and functional neuroimaging studies of TD implicate not only the
      sensorimotor corticostriatal circuit, but also the limbic and associative
      circuits as well. Preliminary evidence also points to abnormalities in the
      frontoparietal network that is thought to maintain adaptive online control.
      Evidence supporting abnormalities in dopaminergic and noradrenergic
      neurotransmission remains strong, although the precise mechanisms remain the
      subject of speculation. CONCLUSION: Structural and functional abnormalities in
      multiple parallel corticostriatal circuits may underlie the behavioral
      manifestations of TD and related neuropsychiatric disorders over the course of
      development. Further longitudinal research is needed to elucidate these
      neurobiological substrates.

PMID- 20807065
TI  - Association between antipsychotics and body mass index when treating patients
      with tics.
AB  - OBJECTIVE: Treatment with antipsychotics can be associated with weight gain, and
      second-generation (atypical) antipsychotics (SGAs) can increase the risk for
      diabetes and dyslipidemia. These risks have not been assessed in patients with
      tics, who receive lower doses than those used to treat psychosis. The objective
      of this study is to investigate the relationship between antipsychotic use and
      weight in tic patients and compare the effects of SGAs to first-generation
      (typical) antipsychotics (FGAs). METHODS: We studied the association between
      antipsychotic use and body mass index (BMI) in consecutive patients with tics
      seen in a specialty Movement Disorders clinic. RESULTS: Height and weight were
      recorded on 198 patients, average age 19.9 years+/-14.0 years, 128 treated and 70
      not treated with antipsychotics. Standardized measures of BMI were significantly
      higher in the antipsychotic-treated patients compared to the untreated patients
      (0.56+/-1.10) treated vs. untreated (-0.31+/-0.82). This difference remained
      significant after controlling for age, gender, stimulant medications, and co
      morbidities such as attention-deficit/hyperactivity disorder (ADHD) and obsessive
      compulsive disorder (OCD). Concomitant medications did not independently
      influence weight, and there was no difference between FGAs and SGAs.
      Antipsychotic dose, expressed in chlorpromazine (CPZ) equivalents, and treatment
      duration did not influence weight. CONCLUSION: Patients with tics on either FGAs
      or SGAs have higher BMI values compared to patients on no antipsychotics. Better
      knowledge of this risk should guide physician decision making when treating
      patients with tics.

PMID- 20807066
TI  - Testing tic suppression: comparing the effects of dexmethylphenidate to no
      medication in children and adolescents with attention-deficit/hyperactivity
      disorder and Tourette's disorder.
AB  - OBJECTIVE: The aim of this study was to conduct a pilot study testing whether
      single-dose, immediate-release dexmethylphenidate (dMPH) can facilitate tic
      suppression in children and adolescents with attention-deficit/hyperactivity
      disorder (ADHD) and Tourette's disorder (TD) or chronic tic disorders. The
      primary hypothesis is that dMPH will improve behaviorally reinforced tic
      suppression in a standard tic suppression paradigm (TSP). METHODS: Ten children
      with ADHD and TD were given dMPH on one visit and no medication on another, using
      a random crossover design. On both days, following a baseline period, subjects
      were reinforced for suppressing tics using a standard TSP. RESULTS: Thirteen
      subjects were enrolled; 10 subjects (mean age 12.7 +/- 2.6; 90% male) completed
      all study procedures. Relative to the no-medication condition, tics were reduced
      when children were given a single dose of dMPH. Behavioral reinforcement of tic
      suppression resulted in lower rates of tics compared to baseline, but dMPH did
      not enhance this suppression. CONCLUSION: Preliminary results indicate
      replication of prior studies of behavioral tic suppression in youths with TD and
      without ADHD. In addition, our findings indicate tic reduction (and not tic
      exacerbation) with acute dMPH challenge in children and adolescents with ADHD and
      TD.

PMID- 20807067
TI  - Effectiveness and tolerability of aripiprazole in children and adolescents with
      Tourette's disorder: a pilot study in China.
AB  - OBJECTIVE: The primary aim of the study was to evaluate the effectiveness and
      tolerability of aripiprazole on motor and vocal tics in children and adolescents
      with Tourette's disorder (TD). The secondary aim was to assess the response of TD
      associated behaviors to aripiprazole exposure. METHODS: This was an 8-week, open
      label trial with flexible dosing strategy of aripiprazole in children and
      adolescents with TD. A total of 72 patients, aged 6-18 years, participated in the
      8-week trial. The Yale Global Tic Severity Scale (YGTSS), the Clinical Global
      Impressions-Tics (CGI-Tics), and the Child Behavior Checklist (CBCL) were
      compared at the baseline, weeks 2 and 4, and end point. The side effects of
      aripiprazole, electrocardiogram (ECG), and body mass index (BMI) were evaluated.
      RESULTS: Over the 8-week trial, aripiprazole administration was associated with a
      significant decrease in total tic severity as measured by the YGTSS (50.3%
      reduction by week 8). The mean scores of motor tic in the YGTSS were 17.42 +/-
      4.83, 12.93 +/- 3.76, 8.39 +/- 3.70, and 6.75 +/- 3.95 at baseline, weeks 2 and
      4, and end point. A significant decrease in the scores was observed in week 2
      compared to the baseline, and the scores continued to decrease for the remainder
      of the study period (degrees of freedom [df ] = 3, F = 96.02, p = 0.000). The
      mean phonic tic scores were 12.71 +/- 4.60, 8.53 +/- 3.26, 6.10 +/- 2.50, and
      3.63 +/- 2.20 at baseline, weeks 2 and 4, and end point, respectively. A
      significant change was observed during week 2 compared to the baseline, and this
      change continued for the rest of the study period (df = 3, F = 95.16, p = 0.000).
      Significant improvement was also observed according to the CGI-Tics severity. The
      mean CGI-Tics severity score was 4.77 +/- 1.69 at baseline and decreased to 2.20
      +/- 1.39 at end point (t = 10.70, p = 0.000). A significant reduction of behavior
      symptoms was noticed according to the CBCL and its subscales between baseline and
      end point. The majority of subjects tolerated aripiprazole well. The
      extrapyramidal symptoms (EPS) during this study were negligible. In all 21
      (29.2%) of the 72 participants complained of nausea and 19 (26.4%) of them
      reported sedation. There was no significant difference of BMI between the two
      phases (df = 64, t = -0.94, p = 0.352). There were no significant changes in
      laboratory results. ECG monitoring revealed no significant impact on cardiac
      conduction by aripiprazol. CONCLUSION: In this preliminary open-label trial,
      aripiprazole showed effectiveness in treating tic symptoms without causing
      significant weight gain or other serious side effects. Aripiprazole could be an
      option for TD cases that do not respond to conventional therapies. Further
      controlled, double-blind studies are warranted.

PMID- 20807068
TI  - Treatment of pediatric obsessive-compulsive disorder: a review.
AB  - Recently, research in pediatric obsessive-compulsive disorder (OCD) has expanded
      to include large family genetic studies, elaboration of phenotypic dimensions,
      description of co-morbid disorders and their moderating effects on treatment
      response and outcome, research on immune-based neuropsychiatric causes,
      randomized controlled trials of selective serotonin reuptake inhibitors (SSRIs),
      randomized controlled trials of cognitive behavioral therapy (CBT), comparative
      treatment trials; new approaches in behavior therapy, and increased awareness of
      newer approaches to treatment. The purpose of this article is to review
      assessment and treatment strategies to include current advances in research.

PMID- 20807069
TI  - Review of the use of the glutamate antagonist riluzole in psychiatric disorders
      and a description of recent use in childhood obsessive-compulsive disorder.
AB  - The antiglutamatergic drug riluzole (Rilutek) is presently being used off label
      in the treatment of psychiatric conditions in adult patients and, increasingly,
      in children. This article briefly reviews the pharmacology of this drug and its
      current investigative and clinical uses and adverse effects. It also reports on
      our experience to date in the study of the drug in children, with emphasis on
      adverse effects noted so far in these younger patients.

PMID- 20807071
TI  - Comparison of clinical characteristics of pediatric autoimmune neuropsychiatric
      disorders associated with streptococcal infections and childhood obsessive
      compulsive disorder.
AB  - OBJECTIVE: The objectives of this study were to identify unique clinical
      characteristics of children with pediatric autoimmune neuropsychiatric disorders
      associated with streptococcal infections (PANDAS) compared with a control group
      of children with non-PANDAS obsessive-compulsive disorder (OCD) with respect to
      ancillary symptoms, types of obsessions and compulsions, symptom severity, and co
      morbid DSM-IV diagnoses. METHOD: Classification of PANDAS was based on review of
      pediatric and psychiatric records using the criteria developed by Swedo and
      colleagues. Children aged 6-14 with PANDAS (n = 21) and non-PANDAS OCD (n = 18)
      were assessed by blind independent evaluators using the PANDAS Questionnaire,
      Children's Yale-Brown Obsessive Compulsive Scale, Yale Global Tic Severity Scale,
      and Anxiety Disorders Interview Schedule for DSM-IV. RESULTS: PANDAS children
      were significantly more likely to present with separation anxiety, urinary
      urgency, hyperactivity, impulsivity, deterioration in handwriting, and decline in
      school performance during their initial episode of neuropsychiatric illness
      compared with children with OCD. Total tics and vocal tics were more severe in
      PANDAS children. Separation anxiety disorder and social phobia were more
      prevalent in non-PANDAS OCD children. Children with non-PANDAS OCD were
      significantly more likely to include others in their rituals. There were no
      significant differences between groups on demographics or severity of OCD.
      CONCLUSIONS: Distinguishing clinical characteristics in PANDAS, which included
      urinary urgency, hyperactivity, impulsivity, and deterioration in handwriting,
      are linked to basal ganglia functions. These clinical characteristics will aid in
      the differentiation of PANDAS children for research and clinical purposes and
      ultimately advance our understanding and treatment of this disorder.

PMID- 20807073
TI  - Bipolar disorder or substance-induced mood disorder in an adolescent?

PMID- 20807074
TI  - Disinhibition as a side effect of treatment with fluvoxamine in pediatric
      patients with obsessive-compulsive disorder.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are usually well tolerated in the
      pediatric population, and widely used in the treatment of obsessive-compulsive
      disorder (OCD). Of the 51 pediatric patients with obsessive-compulsive disorder
      seen in our outpatient clinic between January 2009 and July 2009, 3 of them
      developed behavioral disinhibition after treatment with fluvoxamine. These cases
      are described and discussed in relation to the use of CYP2D6 and CYP2C19
      pharmacogenetic testing in patients treated with serotonin-selective reuptake
      inhibitors.

PMID- 20807070
TI  - The immunobiology of Tourette's disorder, pediatric autoimmune neuropsychiatric
      disorders associated with Streptococcus, and related disorders: a way forward.
AB  - Obsessive-compulsive disorder (OCD) and related conditions including Tourette's
      disorder (TD) are chronic, relapsing disorders of unknown etiology associated
      with marked impairment and disability. Associated immune dysfunction has been
      reported and debated in the literature since the late 80s. The immunologic
      culprit receiving the most interest has been Group A Streptococcus (GAS), which
      began to receive attention as a potential cause of neuropsychiatric symptoms,
      following the investigation of the symptoms reported in Sydenham's chorea (SC)
      and rheumatic fever, such as motor tics, vocal tics, and both obsessive
      compulsive and attention deficit/hyperactivity symptoms. Young children have been
      described as having a sudden onset of these neuropsychiatric symptoms temporally
      associated with GAS, but without supporting evidence of rheumatic fever. This
      presentation of OCD and tics has been termed pediatric autoimmune
      neuropsychiatric disorders associated with Streptococcus (PANDAS). Of note, SC,
      OCD, and TD often begin in early childhood and share common anatomic areas--the
      basal ganglia of the brain and the related cortical and thalamic sites--adding
      support to the possibility that these disorders might share a common immunologic
      and/or genetic vulnerability. Relevant manuscripts were identified through
      searches of the PsycINFO and MedLine databases using the following keywords: OCD,
      immune, PANDAS, Sydenham chorea, Tourette's disorder Group A Streptococcus.
      Articles were also identified through reference lists from research articles and
      other materials on childhood OCD, PANDAS, and TD between 1966 and December 2010.
      Considering the overlap of clinical and neuroanatomic findings among these
      disorders, this review explores evidence regarding the immunobiology as well as
      the relevant clinical and therapeutic aspects of TD, OCD, and PANDAS.

PMID- 20807075
TI  - Reduction of seasonal influenza transmission among healthcare workers in an
      intensive care unit: a 4-year intervention study in Thailand.
AB  - OBJECTIVE: To evaluate the feasibility and effectiveness of an influenza control
      bundle to minimize healthcare-associated seasonal influenza transmission among
      healthcare workers (HCWs) in an intensive care unit (ICU) equipped with central
      air conditioning. METHODS: A quasi-experimental study was conducted in a 500-bed
      tertiary care center in Thailand from July 1, 2005, through June 30,2009. The
      medical ICU (MICU) implemented an influenza control bundle including healthcare
      worker (HCW) education, influenza screening of adult community-acquired pneumonia
      patients, antiviral treatment of patients and ill HCWs who tested positive for
      influenza, promotion of influenza vaccination among HCWs, and reinforcement of
      standard infection control policies. The surgical ICU (SICU) and coronary care
      unit (CCU) received no intervention. RESULTS: The numbers of influenza infections
      among HCWs during the pre- and postintervention periods were 18 cases in 5,294
      HCW days and 0 cases in 5,336 HCW-days in the MICU (3.4 vs 0 cases per 1,000 HCW
      days; P ! .001), 19 cases in 4,318 HCW-days and 20 cases in 4,348 HCW-days in the
      SICU (4.4 vs 4.6 cases per 1,000 HCW-days; Pp.80), and 18 cases in 5,000 HCW-days
      and 18 cases in 5,143 HCW-days in the CCU (3.6 vs 3.5 cases per 1,000 HCW-days;
      Pp.92), respectively. Outbreak-related influenza occurred in 7 MICUHCWs, 6 SICU
      HCWs, and 4 CCU HCWs before intervention and 0 MICU HCWs, 9 SICU HCWs, and 8 CCU
      HCWs after intervention.Before and after intervention, 25 (71%) and 35 (100%) of
      35 MICU HCWs were vaccinated, respectively (P ! .001); HCW vaccination coverage
      did not change significantly in the SICU (21 [70%] of 30 vs 24 [80%] of 30;
      Pp.89) and CCU (19 [68%] of 28 vs 21 [75%]of 28; Pp.83). The estimated costs of
      US $6,471 per unit for postintervention outbreak investigations exceeded the
      intervention costs of US $4,969. CONCLUSION: A sustained influenza intervention
      bundle was associated with clinical and economic benefits to a Thai hospital.

PMID- 20807076
TI  - Why are there seizures in neurocysticercosis: is it in the genes?

PMID- 20807077
TI  - Toll-like receptor 4 polymorphism and its association with symptomatic
      neurocysticercosis.
AB  - BACKGROUND: Symptoms and signs of neurocysticercosis (NCC) are nonspecific and
      depend upon several factors, including the host immune response to the parasite.
      Toll-like receptors (TLRs) play an important role in innate immunity.
      Susceptibility of humans to NCC in relation to TLR polymorphism is unknown. The
      present study examines TLR4 polymorphism in human NCC and its role in symptomatic
      disease. METHODS: A total of 140 patients with NCC (82 symptomatic [ie, with
      active epilepsy] and 58 asymptomatic) and 150 healthy control subjects were
      examined for TLR4 Asp299Gly and Thr399Ile polymorphisms by means of polymerase
      chain reaction and restriction fragment-length polymorphism. RESULTS: TLR4
      Asp299Gly and Thr399Ile were significantly associated with the occurrence of NCC
      (P < .001 for Asp299Gly; P = .003 for Thr399Ile) and progression to symptomatic
      NCC, compared with control subjects (P < .001 for Asp299Gly; P < .001 for
      Thr399Ile) or asymptomatic NCC (P < .001 for Asp299Gly; P = .002 for Thr399Ile).
      Frequency of haplotype Gly/Thr (P <.001) was observed to be a risk factor for
      susceptibility to NCC. Gly and Ile carriers had a statistically significant
      association with NCC (P < .001 for Gly; P = .003 for Ile) and symptomatic NCC (P
      < .001 for Gly; P <or= .001 for Ile), compared with control subjects. Both
      carriers were also associated with symptomatic NCC (P < .001 for Gly; P < .004
      for Ile), when compared with asymptomatic NCC.

PMID- 20807078
TI  - A probabilistic analysis of a simplified biogeography-based optimization
      algorithm.
AB  - Biogeography-based optimization (BBO) is a population-based evolutionary
      algorithm (EA) that is based on the mathematics of biogeography. Biogeography is
      the study of the geographical distribution of biological organisms. We present a
      simplified version of BBO and perform an approximate analysis of the BBO
      population using probability theory. Our analysis provides approximate values for
      the expected number of generations before the population's best solution
      improves, and the expected amount of improvement. These expected values are
      functions of the population size. We quantify three behaviors as the population
      size increases: first, we see that the best solution in the initial randomly
      generated population improves; second, we see that the expected number of
      generations before improvement increases; and third, we see that the expected
      amount of improvement decreases.

PMID- 20807079
TI  - Modeling the performance of evolutionary algorithms on the root identification
      problem: a case study with PBIL and CHC algorithms.
AB  - The availability of a model to measure the performance of evolutionary algorithms
      is very important, especially when these algorithms are applied to solve problems
      with high computational requirements. That model would compute an index of the
      quality of the solution reached by the algorithm as a function of run-time.
      Conversely, if we fix an index of quality for the solution, the model would give
      the number of iterations to be expected. In this work, we develop a statistical
      model to describe the performance of PBIL and CHC evolutionary algorithms applied
      to solve the root identification problem. This problem is basic in constraint
      based, geometric parametric modeling, as an instance of general constraint
      satisfaction problems. The performance model is empirically validated over a
      benchmark with very large search spaces.

PMID- 20807080
TI  - Constrained evolutionary optimization by means of (MU + lambda)-differential
      evolution and improved adaptive trade-off model.
AB  - This paper proposes a (MU + lambda)-differential evolution and an improved
      adaptive trade-off model for solving constrained optimization problems. The
      proposed (MU + lambda)-differential evolution adopts three mutation strategies
      (i.e., rand/1 strategy, current-to-best/1 strategy, and rand/2 strategy) and
      binomial crossover to generate the offspring population. Moreover, the current-to
      best/1 strategy has been improved in this paper to further enhance the global
      exploration ability by exploiting the feasibility proportion of the last
      population. Additionally, the improved adaptive trade-off model includes three
      main situations: the infeasible situation, the semi-feasible situation, and the
      feasible situation. In each situation, a constraint-handling mechanism is
      designed based on the characteristics of the current population. By combining the
      (MU + lambda)-differential evolution with the improved adaptive trade-off model,
      a generic method named (MU + lambda)-constrained differential evolution ((MU +
      lambda)-CDE) is developed. The (MU + lambda)-CDE is utilized to solve 24 well
      known benchmark test functions provided for the special session on constrained
      real-parameter optimization of the 2006 IEEE Congress on Evolutionary Computation
      (CEC2006). Experimental results suggest that the (MU + lambda)-CDE is very
      promising for constrained optimization, since it can reach the best known
      solutions for 23 test functions and is able to successfully solve 21 test
      functions in all runs. Moreover, in this paper, a self-adaptive version of (MU +
      lambda)-CDE is proposed which is the most competitive algorithm so far among the
      CEC2006 entries.

PMID- 20807081
TI  - A ripple-spreading genetic algorithm for the aircraft sequencing problem.
AB  - When genetic algorithms (GAs) are applied to combinatorial problems, permutation
      representations are usually adopted. As a result, such GAs are often confronted
      with feasibility and memory-efficiency problems. With the aircraft sequencing
      problem (ASP) as a study case, this paper reports on a novel binary
      representation-based GA scheme for combinatorial problems. Unlike existing GAs
      for the ASP, which typically use permutation representations based on aircraft
      landing order, the new GA introduces a novel ripple-spreading model which
      transforms the original landing-order-based ASP solutions into value-based ones.
      In the new scheme, arriving aircraft are projected as points into an artificial
      space. A deterministic method inspired by the natural phenomenon of ripple
      spreading on liquid surfaces is developed, which uses a few parameters as input
      to connect points on this space to form a landing sequence. A traditional GA,
      free of feasibility and memory-efficiency problems, can then be used to evolve
      the ripple-spreading related parameters in order to find an optimal sequence.
      Since the ripple-spreading model is the centerpiece of the new algorithm, it is
      called the ripple-spreading GA (RSGA). The advantages of the proposed RSGA are
      illustrated by extensive comparative studies for the case of the ASP.

PMID- 20807082
TI  - On the behaviour of evolution strategies optimising cigar functions.
AB  - This paper studies the performance of multi-recombinative evolution strategies
      using isotropically distributed mutations with cumulative step length adaptation
      when applied to optimising cigar functions. Cigar functions are convex-quadratic
      objective functions that are characterised by the presence of only two distinct
      eigenvalues of their Hessian, the smaller one of which occurs with multiplicity
      one. A simplified model of the strategy's behaviour is developed. Using it,
      expressions that approximately describe the stationary state that is attained
      when the mutation strength is adapted are derived. The performance achieved by
      cumulative step length adaptation is compared with that obtained when using
      optimally adapted step lengths.

PMID- 20807083
TI  - On the optimal convergence probability of univariate estimation of distribution
      algorithms.
AB  - In this paper we obtain bounds on the probability of convergence to the optimal
      solution for the compact genetic algorithm (cGA) and the population based
      incremental learning (PBIL). Moreover, we give a sufficient condition for
      convergence of these algorithms to the optimal solution and compute a range of
      possible values for algorithm parameters at which there is convergence to the
      optimal solution with a predefined confidence level.

PMID- 20807084
TI  - Hyperbolic mixed-type inhibition of acetylcholinesterase by tetracyclic
      thienopyrimidines.
AB  - A series of tetracyclic thienopyrimidines (7-14) was prepared and investigated as
      inhibitors of acetylcholinesterase from Electrophorus electricus
      acetylcholinesterase (EeAChE), as well as human acetylcholinesterase (hAChE) and
      human butyrylcholinesterase (hBChE). A new synthetic procedure was employed for
      the synthesis of the angularly fused heterocycles 7-10. Among them, the presence
      of a tetrahydropyrido ring with a benzyl rest at the basic nitrogen was required
      for EeAChE inhibition. A detailed kinetic analysis of the hyperbolic mixed-type
      inhibition of EeAChE by 9-14 was performed. These heterocyclic compounds
      inhibited EeAChE with K(i) values of less than 3 uM. Most alpha values were
      relatively close to 1, indicating a similar affinity of the inhibitor to the free
      enzyme and the enzyme-substrate complex. Inhibitor 10 displayed a rather
      uncompetitive pattern of inhibition (alpha = 0.47) and a relatively high residual
      activity of a postulated ternary enzyme-substrate-inhibitor complex (beta =
      0.24).

PMID- 20807085
TI  - Kinetic prerequisites of oximes as effective reactivators of organophosphate
      inhibited acetylcholinesterase: a theoretical approach.
AB  - The standard treatment of poisoning by organophosphorus compounds (OP) includes
      the reversible muscarine receptor antagonist atropine and oximes for the
      reactivation of OP-inhibited acetylcholinesterase (AChE). There is an ongoing
      discussion on the benefit of oxime therapy in OP pesticide poisoning, and
      experimental data indicate a limited efficacy of oximes against various nerve
      agents. Oxime effectiveness can be quantified in vitro by determination of the
      reactivity (k(r)) and affinity constants (1/K(D)). These constants can be used to
      calculate reactivation velocities and oxime concentrations necessary for the
      reactivation of a desired fraction of inhibited AChE. Model calculations indicate
      that a k(r) > 0.1 min(-1) and K(D) < 100 uM are minimal requirements for oxime
      effectiveness when reactivation is performed in the absence of free OP. In
      addition, the findings demonstrate that selective increase of either reactivity
      or affinity of an oxime would be insufficient. Hereby, it has to be taken into
      account that an increase of affinity to OP-inhibited AChE is generally
      accompanied by an increased affinity to native AChE and subsequent reduction in
      oxime tolerance. Hence, future developments of more effective oximes should
      consider kinetic demands by attempting to achieve a certain level of reactivity
      and affinity, preferentially towards OP-inhibited AChE.

PMID- 20807086
TI  - Synthesis and in vitro antimicrobial activity of novel N-(6-chlorobenzo[d]thiazol
      2-yl) hydrazine carboxamide derivatives of benzothiazole class.
AB  - In this study, a series of novel 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole (6a-g)
      and 1,3,4-oxadiazole (7a-g, 8) were synthesized from N-(6-chlorobenzo[d]thiazol-2
      yl) hydrazine carboxamide derivatives of benzothiazole class. Antimicrobial
      properties of the title compound derivatives were investigated against one Gram
      (+) bacteria (Staphylococcus aureus), three Gram (-) bacteria (Escherichia coli,
      Pseudomonas aeruginosa, Klebsiella pneumoniae) and five fungi (Candida albicans,
      Aspergillus niger, Aspergillus flavus, Monascus purpureus and Penicillium
      citrinum) using serial plate dilution method. The investigation of antibacterial
      and antifungal screening data revealed that all the tested compounds showed
      moderate to good inhibition at 12.5-100 ug/mL in DMSO. It has been observed that
      triazolo-thiadiazole derivatives are found to be more active than 1,3,4
      oxadiazole derivatives against all pathogenic bacterial and fungal strains.

PMID- 20807087
TI  - European Myeloma Network: the 3rd Trialist Forum Consensus Statement from the
      European experts meeting on multiple myeloma.
AB  - Over the past two decades, not only treatment options, but also the diagnosis,
      staging, and risk assessment of multiple myeloma (MM), have undergone significant
      development, partially due to a deeper understanding of MM pathogenesis.
      Conventional cytogenetics and fluorescence in situ hybridization are routinely
      assessed in MM, and when combined with ISS stage may attain an even better
      predictive potential. In order to achieve even more effective and individualized
      therapies, one crucial goal is the identification of genes and gene combinations
      that predict for response or resistance to chemotherapy. High-dose chemotherapy
      with autologous stem cell transplant (SCT) still remains the standard therapy for
      younger patients, with novel agents now being included in both pre-transplant
      regimens and post-transplant consolidation/maintenance approaches. Similarly,
      novel agents are also being incorporated into allogeneic SCT for selected
      patients. In the treatment of elderly patients with MM, novel agents have been
      successfully incorporated into less intensive regimens, including
      melphalan/prednisone, low-dose dexamethasone, and cyclophosphamide/dexamethasone.
      While second-generation proteasome inhibitors are currently being intensively
      investigated, the subcutaneous administration of bortezomib, being equivalent to
      the established i.v. route, is now entering clinical practice. Supportive care
      remains a crucial aspect in the management of MM. The European Myeloma Network
      Trialist Group aims to address these contemporary aspects in MM.

PMID- 20807088
TI  - Long-term response to maintenance treatment with rituximab in CD20(+) multiple
      myeloma.

PMID- 20807089
TI  - Ocular adnexal mucosa-associated lymphoid tissue lymphoma in Northern China: high
      frequency of numerical chromosomal changes and no evidence of an association with
      Chlamydia psittaci.
AB  - Studies from different countries showed variations of genetic changes and
      association with Chlamydia psittaci in ocular adnexal mucosa-associated lymphoid
      tissue (MALT) lymphoma. A total of 38 ocular adnexal MALT lymphoma cases from
      Northern China were studied. Genetic abnormalities were investigated in 28 cases
      by interphase FISH. C. psittaci and other infectious agents that are commonly
      associated with chronic eye disease were screened in 38 cases by PCR. Genetic
      abnormalities were detected in 60.7% of cases. Among them, only one showed a
      break-apart of the IgH gene and all others showed numerical abnormalities,
      including trisomy 18 in 7 cases (25%), 3 copies of BCL6 gene in 12 cases (43%),
      and 3 copies of C-MYC gene in 2 cases (7%). C. pneumoniae was positive in two
      cases (5.3%), and C. psittaci, C. trachomatis, HSV1, HSV2, ADV8, and ADV19 were
      not detected in any cases. In conclusion, numerical abnormalities are frequent
      and the chromosomal translocations commonly associated with MALT lymphomas are
      rare in ocular adnexal MALT lymphoma of Northern China. C. psittaci and other
      infectious agents are not associated with ocular adnexal MALT lymphoma in these
      patients.

PMID- 20807090
TI  - Prognostic markers in diffuse large B-cell lymphoma.

PMID- 20807091
TI  - Obesity and lymphoma therapy: not a bad combination after all.

PMID- 20807092
TI  - Hepatitis-B reactivation and rituximab-containing chemotherapy: an increasingly
      complex clinical challenge.

PMID- 20807093
TI  - Body mass index and outcomes in patients receiving chemotherapy for intermediate
      grade B-cell non-Hodgkin lymphoma.
AB  - We conducted a retrospective cohort study examining the influence of obesity on
      treatment outcome and survival among 712 patients with intermediate-grade B-cell
      NHL receiving frontline therapy between 1988 and 2001. Baseline adiposity was
      approximated by body mass index categorized according to the World Health
      Organization schema. Logistic and Cox proportional hazards regression modeling
      was used to adjust for baseline patient demographic, disease, and treatment
      variables. Approximately 37% of cohort patients were overweight (BMI 25 to <30
      kg/m(2)) and more than 23% were obese (BMI >or= 30 kg/m(2)). Risk factors were
      similar across groups and treatment intensity did not vary by BMI. Median follow
      up was 45.7 and 62.8 months for PFS and OS, respectively. After adjustment for
      other significant prognostic factors, BMI in the overweight range was associated
      with significantly reduced hazard for both PFS (OR 0.72, p = 0.011) and OS (OR
      0.74, p = 0.030). Increased BMI is associated with significantly improved
      survival among patients with treatment-naive, intermediate-grade B-cell NHL.
      Prospective confirmation of these results is warranted given the increasing
      prevalence of both NHL and obesity.

PMID- 20807095
TI  - Prognostic analysis of acute exacerbations of hepatitis-B after chemotherapy in
      combination with rituximab in 19 patients with lymphoma.
AB  - The prognosis and management of acute exacerbations of hepatitis-B in patients
      with lymphoma after chemotherapy in combination with rituximab remain unclear.
      Here, we describe 19 Chinese patients with lymphoma who suffered this
      complication, in order to analyze their clinical characteristics. Receiver
      operating characteristic analysis and Kaplan-Meier survival analysis were
      utilized to determine potential prognostic factors. We found that key prognostic
      factors included the peak prothrombin time (PT), international normalized ratio
      (INR), and total bilirubin (TB), as well as the PT and INR on admission and the
      interval between acute exacerbation of hepatitis-B and the last cycle of
      chemotherapy. Moreover, our data suggested that shorter interval between the last
      cycle of rituximab and acute exacerbation of hepatitis-B might be another
      prognostic indicator of inferior survival. Our results revealed that the severity
      of hepatic damage and the interval between the last cycle of chemotherapy and
      hepatitis flare were the major prognostic factors of an acute exacerbation of
      hepatitis-B induced by immunochemotherapy. Prophylactic antiviral and rescue
      antiviral therapy remain to be further characterized.

PMID- 20807094
TI  - Comparison of two high-dose cyclophosphamide, doxorubicin, vincristine, and
      prednisone derived regimens in patients aged under 60 years with low-intermediate
      risk aggressive lymphoma: a final analysis of the multicenter LNH93-2 protocol.
AB  - One-third of patients aged <or=60 years with aggressive lymphoma are at low
      intermediate risk (LIR). Before the rituximab era, we prospectively compared
      ACVBP with ECVBP, a similar regimen including epirubicin instead of doxorubicin
      and increased dose intensity of cyclophosphamide, followed by conventional
      consolidation with an increased amount and dose intensity of cytosine
      arabinoside, methotrexate, etoposide, and ifosfamide, in 652 patients with LIR
      aggressive lymphoma. The overall response rate, 5-year event-free survival (EFS),
      and survival were estimated to be 86%, 60%, and 74%, respectively, with no
      differences between the two arms. In patients with diffuse large B-cell lymphoma
      (DLBCL) who received ACVBP, the 5-year EFS and survival were estimated at 69% and
      82%. These findings do not support the use of a chemotherapy regimen more
      intensive than ACVBP in patients aged <or=60 years with LIR aggressive lymphoma.
      The results in the control arm, without rituximab, have led to a randomized
      comparison of R-ACVBP and R-CHOP in this patient population.

PMID- 20807096
TI  - PTEN tumor suppressor plays less prognostic role than P53 tumor suppressor in
      diffuse large B-cell lymphoma.
AB  - The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and P53 tumor
      suppressors are among the most commonly inactivated or mutated genes in human
      cancers, whose pathways cross-talk and interact in a complementary mode. In order
      to understand their roles and relationship in diffuse large B-cell lymphoma
      (DLBCL), we examined their expression and evaluated their prognostic significance
      in 62 patients with DLBCL treated with standard chemotherapy. Results showed that
      PTEN protein was lost in 23 (37.1%) cases, and the loss was associated with the
      activation of PI3K/AKT pathway, but was not associated with patient's clinical
      outcome. P53 mutation protein was detected in 30 (48.4%) cases and was associated
      with poor survival. Results of multivariate analysis showed that P53 mutation but
      not PTEN loss is associated with short survival in patients with DLBCL. PTEN
      status has no effect on P53 mutation-associated poor survival. We conclude that
      PTEN may play less prognostic role than P53 and that P53 mutation protein should
      be considered as a predictive factor of the need for a more aggressive therapy in
      patients with DLBCL who express P53.

PMID- 20807097
TI  - Monomorphic T-cell post-transplant lymphoproliferative disorders exhibit markedly
      inferior outcomes compared to monomorphic B-cell post-transplant
      lymphoproliferative disorders.

PMID- 20807098
TI  - From synapses to behavior: neurobiology in Drosophila.

PMID- 20807099
TI  - Synaptic vesicle recycling: genetic and cell biological studies.
AB  - We review mainly the work from our research group here. Our focus has been on the
      use of genetic methods to delineate the mechanisms of synaptic vesicle recycling
      and cellular trafficking. Acute temperature-sensitive paralytic mutants have been
      of particular value in this approach. We have primarily used screens for
      suppressor and enhancer mutations to identify genetic loci coding for proteins
      that interact with Dynamin in Drosophila. In addition, we have used reverse
      genetic approaches to investigate few other candidate molecules that may play a
      role in synaptic vesicle endocytosis. We have in particular discussed at some
      length the role of endocytic accessory proteins Stoned and Eps15 in vesicle
      recycling.

PMID- 20807100
TI  - Adaptive adjustment of the generalization-discrimination balance in larval
      Drosophila.
AB  - Learnt predictive behavior faces a dilemma: predictive stimuli will never
      'replay' exactly as during the learning event, requiring generalization. In turn,
      minute differences can become meaningful, prompting discrimination. To provide a
      study case for an adaptive adjustment of this generalization-discrimination
      balance, the authors ask whether Drosophila melanogaster larvae are able to
      either generalize or discriminate between two odors (1-octen-3-ol and 3-octanol),
      depending on the task. The authors find that after discriminatively rewarding one
      but not the other odor, larvae show conditioned preference for the rewarded odor.
      On the other hand, no odor specificity is observed after nondiscriminative
      training, even if the test involves a choice between both odors. Thus, for this
      odor pair at least, discrimination training is required to confer an odor
      specific memory trace. This requires that there is at least some difference in
      processing between the two odors already at the beginning of the training.
      Therefore, as a default, there is a small yet salient difference in processing
      between 1-octen-3-ol and 3-octanol; this difference is ignored after
      nondiscriminative training (generalization), whereas it is accentuated by odor
      specific reinforcement (discrimination). Given that, as the authors show, both
      faculties are lost in anosmic Or83b(1) mutants, this indicates an adaptive
      adjustment of the generalization-discrimination balance in larval Drosophila,
      taking place downstream of Or83b-expressing sensory neurons.

PMID- 20807102
TI  - The effect of simulated microgravity on human mesenchymal stem cells cultured in
      an osteogenic differentiation system: a bioinformatics study.
AB  - One proposed strategy for bone regeneration involves ex vivo tissue engineering,
      accomplished using bone-forming cells, biodegradable scaffolds, and dynamic
      culture systems, with the goal of three-dimensional tissue formation. Rotating
      wall vessel bioreactors generate simulated microgravity conditions ex vivo, which
      lead to cell aggregation. Human mesenchymal stem cells (hMSCs) have been
      extensively investigated and shown to possess the potential to differentiate into
      several cell lineages. The goal of the present study was to evaluate the effect
      of simulated microgravity on all genes expressed in hMSCs, with the underlying
      hypothesis that many important pathways are affected during culture within a
      rotating wall vessel system. Gene expression was analyzed using a whole genome
      microarray and clustering with the aid of the National Institutes of Health's
      Database for Annotation, Visualization and Integrated Discovery database and gene
      ontology analysis. Our analysis showed 882 genes that were downregulated and 505
      genes that were upregulated after exposure to simulated microgravity. Gene
      ontology clustering revealed a wide variety of affected genes with respect to
      cell compartment, biological process, and signaling pathway clusters. The data
      sets showed significant decreases in osteogenic and chondrogenic gene expression
      and an increase in adipogenic gene expression, indicating that ex vivo adipose
      tissue engineering may benefit from simulated microgravity. This finding was
      supported by an adipogenic differentiation assay. These data are essential for
      further understanding of ex vivo tissue engineering using hMSCs.

PMID- 20807105
TI  - Predictors of breastfeeding and breastmilk feeding among very low birth weight
      infants.
AB  - OBJECTIVE: This study investigated associations between maternal and infant
      factors and breastfeeding practices in infants born <30 weeks gestation in the
      neonatal intensive care unit (NICU). STUDY DESIGN: This study was a retrospective
      cohort. Mother and infant characteristics were investigated for associations with
      breastfeeding outcomes using multivariate logistic regression. RESULTS: Seventy
      eight percent of infants initiated breastmilk feedings, 48% of those continued to
      have breastmilk at discharge, and 52% were breastfed in the hospital. The average
      duration of breastmilk feedings was 43 days. Mothers who were married and had a
      multiple-infant birth were more likely to initiate breastmilk feeds, African
      American mothers and younger mothers had less success with maintaining breastmilk
      feeds until hospital discharge, and African American mothers and mothers of lower
      socioeconomic status were less likely to participate in direct breastfeeding in
      the NICU. CONCLUSIONS: Infant factors, such as birth weight and gestational age,
      were not associated with breastfeeding behaviors. Mothers can succeed with
      breastfeeding the premature infant. By understanding what maternal groups are at
      risk for breastfeeding failure, targeted interventions in the NICU can be
      implemented.

PMID- 20807106
TI  - Discontinuation syndrome in newborns whose mothers took antidepressants while
      pregnant or breastfeeding.
AB  - OBJECTIVE: This study compared mothers' report of symptoms of discontinuation
      syndrome in infants exposed to antidepressants both in utero and during lactation
      to infants who were exposed only during lactation. STUDY DESIGN: This is a
      convenience sample of 930 women breastfeeding women who answered an online
      questionnaire about antidepressant use while pregnant and breastfeeding. All 930
      women had taken antidepressants while breastfeeding, and 527 had also taken
      antidepressants during pregnancy. There were no participants in the present study
      who had taken antidepressants only during pregnancy. The questionnaire was posted
      on the first author's Medications and Breastfeeding Forum. There was no
      advertising of this study, nor were efforts made to recruit women into this study
      beyond posting a notice on the website. The questionnaire included a list of
      symptoms that mothers may have observed in their infants during the newborn
      period, as well as demographic questions, and questions about antidepressant use
      during pregnancy and lactation. RESULTS: The majority of women reported that
      their infants never experienced the symptoms of discontinuation syndrome. Twenty
      five percent reported infant irritability. A smaller percentage reported
      inconsolable crying (17%), low body temperature (14%), and significant problems
      with eating and sleeping (15%). Logistic regression revealed that mothers who
      took antidepressants while pregnant and then during breastfeeding were two to
      eight times more likely to report symptoms of discontinuation syndrome than women
      who took them only while breastfeeding. Discontinuation symptoms were more likely
      to occur in infants whose mothers took medications with shorter half-lives.
      CONCLUSIONS: Discontinuation syndrome does occur in a small percentage of infants
      exposed to antidepressants in utero. Mothers reported a higher frequency of
      discontinuation syndrome after in utero exposure followed by breastfeeding than
      when infants were exposed to antidepressants only during lactation.

PMID- 20807104
TI  - Nipple shields: a review of the literature.
AB  - Nipple shields have become commonplace in the United States for a wide range of
      breastfeeding problems. This article is a summary of the current literature
      describing the evidence for nipple shield use. The authors reviewed all available
      articles on nipple shields and selected 13 studies for inclusion. The studies
      were organized into three categories: physiologic responses, premature infants,
      and mothers' experiences. This review concludes that current published research
      does not provide evidence for safety or effectiveness of contemporary nipple
      shield use.

PMID- 20807107
TI  - [Website review]

PMID- 20807108
TI  - Surveillance for foodborne illness outbreaks in Qassim, Saudi Arabia, 2006.
AB  - The objectives of this study were to determine the burden of foodborne illness,
      and to identify the specific foods and causative organisms responsible for
      foodborne illness outbreaks in Qassim, Saudi Arabia, during the year 2006. The
      study is a descriptive analysis of the surveillance data for foodborne illness
      outbreaks, collected by the Preventive Medicine Department, Primary Health Care
      Administration, Qassim province. We analyzed the foodborne illness surveillance
      data for the year 2006, using SPSS-11 statistical package. The distribution of
      foodborne illnesses was examined in relation to age, sex, nationality, and month
      of occurrence. In addition, types of food, place of food preparation, and
      pathogenic agent responsible for the outbreaks were also analyzed. During the
      year 2006, 31 foodborne illness outbreaks, accounting for 251 cases, were
      reported. The highest proportion (64.5%) of outbreaks was reported during summer
      months of June to August. Men constituted 66.9% of the cases, and 68.1% were
      adults. Salmonella species was the commonest causative agent, followed by
      Staphylococcus aureus. The majority (68.9%) of the cases got sick after consuming
      commercially prepared foods. Meat intake caused 67.7% cases, and Middle Eastern
      meat sandwich was a commonly implicated food. Our study concludes that foodborne
      illness is an important public health problem in Qassim province. A comprehensive
      approach is required to assure food safety in commercial food establishments.
      Health education of the community, food handlers, and food industry workers
      regarding food and personal hygiene will reduce the incidence of foodborne
      illnesses in Qassim and Saudi Arabia.

PMID- 20807109
TI  - Bacteriophage-based rapid and sensitive detection of Escherichia coli O157:H7
      isolates from ground beef.
AB  - We investigated the efficacy of bacteriophage-based detection technology to
      detect Escherichia coli O157:H7 from ground beef. The assay involved a short
      enrichment period of 8 h followed by capture of the pathogen on O157-specific
      immunomagnetic beads. The captured cells were treated with O157-specific lytic
      bacteriophage, CSLO157. Upon phage-induced lysis, the enzyme adenylate kinase,
      which was released from the lysed cells, was measured in terms of relative light
      units using luciferin-luciferase assay. The plaque forming efficiency (e.g.,
      phage susceptibility) and ability to capture cells with immunomagnetic beads were
      examined using an array of 74 E. coli O157:H7 isolates obtained from various
      clinical and foodborne samples. Immunmagnetic beads successfully captured all 74
      isolates; however, only 53 isolates showed susceptibility toward the
      bacteriophage. Susceptible isolates were further classified into two broad
      groups, moderately sensitive isolates, which generated phage titer ~ 10(7)pfu/mL
      (group I, n=15), and highly susceptible isolates, which generated high phage
      titer ~ 10(9)pfu/mL (group II, n=38). We selected 15 isolates (9 from group I and
      6 from group II) and individually spiked beef samples (ca. 3-8 cells/25 g beef)
      to evaluate the bacteriophage-based detection system. Eight out of nine isolates
      from group I and all six isolates from group II were successfully detected.
      Pathogenic E. coli strains belonging to other serogroups (12 serogroups, 67
      isolates) as well as nontarget microorganisms (n=18) were not lysed by the
      bacteriophage and hence were not detected. The method is high-throughput
      compatible, is rapid, and can provide live culture the following day by streaking
      an aliquot before phage lysis on conventional selective agar media.

PMID- 20807110
TI  - Large listeriosis outbreak linked to cheese made from pasteurized milk, Germany,
      2006-2007.
AB  - A commercial cheese (acid curd) made from pasteurized milk caused a large
      listeriosis outbreak in Germany from October 2006 through February 2007. The
      Listeria monocytogenes outbreak strain was identified in humans and in cheese
      samples from a patient's home and from the production plant. During the outbreak
      period, 189 patients were affected, which was 97% above the mean case number for
      the respective time period of the years 2002 to 2005. Of patients with available
      detailed information on cheese consumption (n=47), 70% reported to have consumed
      the incriminated cheese product. Recent European food safety alerts due to
      Listeria-contaminated cheeses more often concerned products made from pasteurized
      or heat-treated milk than from raw milk. The findings should be considered in
      prevention guidelines addressing vulnerable populations.

PMID- 20807111
TI  - A foodborne outbreak of Cyclospora infection in Stockholm, Sweden.
AB  - During May and June 2009 an outbreak of Cyclospora cayetanensis infection
      involving 12 laboratory-confirmed and 6 probable cases was detected in Stockholm
      County, Sweden. Imported sugar snap peas from Guatemala were the suspected
      vehicle, based on information obtained from patient questionnaires. This is the
      first reported outbreak of cyclosporiasis in Sweden and the second in Europe.

PMID- 20807112
TI  - High incidence of enterotoxin D producing Staphylococcus spp. in Brazilian cow's
      raw milk and its relation with coagulase and thermonuclease enzymes.
AB  - In this study, the enterotoxigenic potential of Staphylococcus strains (n = 574)
      isolated from raw milk samples (n = 140) was determined for their capacity to
      produce staphylococcal enterotoxins. In addition, the relationship between the
      presence of enterotoxins, coagulase, and thermonuclease (Tnase) was assessed. The
      results showed that 19% of Staphylococcus was enterotoxigenic, being able to
      produce at least one of the staphylococcal enterotoxins (A, B, C, and D). Most of
      the strains were able to produce enterotoxin D (68.8%), whereas 12.8% of the
      Staphylococcus strains were able to produce staphylococcal enterotoxin A.
      Besides, the production of more than one type of enterotoxins by the same strain
      was observed. Tnase was considered the best marker for enterotoxigenic potential
      of isolates, although some of them were negative for coagulase and Tnase but
      positive for enterotoxin production. Therefore, either the use of Tnase to assess
      Staphylococcus enterotoxigenic potential or the use of simple and easy screening
      tests for enterotoxin production should receive more attention when evaluating
      the pathogenic potential of foodborne Staphylococcus strains. Due to the
      association of both coagulase positive Staphylococcus and coagulase negative
      Staphylococcus with foodborne disease outbreaks, regulators and industries should
      pay more attention to enterotoxigenic Staphylococcus rather than focusing only on
      S. aureus or coagulase positive Staphylococcus. Finally, data found here suggest
      a high risk of staphylococcal intoxication with the consumption of raw milk or
      dairy products made from raw milk.

PMID- 20807113
TI  - In vitro effects of pomegranate juice and pomegranate polyphenols on foodborne
      viral surrogates.
AB  - Pomegranate juice (PJ) has gained popularity because of its associated
      antioxidant, antimicrobial, anticancer, and anti-inflammatory properties.
      However, its effects against epidemiologically significant foodborne viruses have
      not been investigated. In the absence of culturable human noroviruses, feline
      calicivirus (FCV-F9), murine norovirus (MNV-1), and MS2 (ssRNA) bacteriophage
      were used as foodborne viral surrogates. The aim of this research was to study
      the effects of PJ and pomegranate polyphenols (PP) on foodborne viral
      infectivity. Viruses at high (~ 7 log(10) PFU/mL) or low (~ 5 log(10) PFU/mL)
      titers were mixed with equal volumes of PJ, 8, 16, and 32 mg/mL of PP, or water
      (control) and incubated for 1 h at room temperature. Viral infectivity after
      treatments was evaluated using standardized plaque assays. PJ decreased the titer
      of FCV-F9, MNV-1, and MS2 by 2.56, 1.32, and 0.32 log(10) PFU/mL, respectively,
      for low titers and 1.20, 0.06, and 0.63 log(10) PFU/mL, respectively, for high
      titers. Interestingly, FCV-F9 was undetectable after exposure to the three tested
      PP solutions using both low and high titers. MNV-1 at low initial titers was
      reduced by 1.30, 2.11, and 3.61 log(10) PFU/mL and at high initial titers by
      1.56, 1.48, and 1.54 log(10) PFU/mL with 4, 8, and 16 mg/mL of PP treatment,
      respectively. MS2 at low initial titers was reduced by 0.41, 0.45, and 0.93
      log(10) PFU/mL and at high initial titers by 0.32, 0.41, and 0.72 log(10) PFU/mL
      after 4, 8, and 16 mg/mL of PP treatment, respectively. PJ and PP resulted in
      titer reductions of foodborne virus surrogates after 1 h exposure, showing
      promise for use in hurdle technologies and/or for therapeutic or preventive use.
      To suggest the use of PJ and PP as natural remedies for foodborne viral illness
      prevention, their mechanism of action against viral infectivity needs to be
      further investigated.

PMID- 20807114
TI  - The effects of sodium orthovanadate-induced phosphatase inhibition on rat retinal
      pigment epithelium cell activity.
AB  - PURPOSE: The purpose of this study was to assess the contribution of sodium
      orthovanadate (SOV)-induced phosphatase inhibition to the activation of rat
      retinal pigment epithelium (RPE) cells. METHODS: Confluent cultures of rat RPE
      cells were treated with the general phosphatase inhibitor SOV. The effects of SOV
      on the cell cycle were determined by flow cytometry and protein detection of
      cyclin A and cyclin D1, two different cell cycle regulatory factors. The effects
      of SOV on cell differentiation were confirmed by immunostaining for alpha-smooth
      muscle actin (alpha-SMA). A migration assay was used to evaluate the effects of
      SOV on cell migration. RESULTS: SOV could accelerate the cell cycle of RPE cells.
      Western blotting showed that SOV significantly increased the expression of cyclin
      A and cyclin D1 in a dose-dependent fashion. The results of alpha-SMA staining
      and western blotting demonstrated that SOV induced RPE cells to differentiate
      toward better contractility and motility. The migration assay indicated that SOV
      improved the migration activity of RPE cells. CONCLUSIONS: Sodium orthovanadate
      can improve proliferation, differentiation, and migration of rat RPE cells and
      can also induce the reentry of contact-inhibited rat RPE cells into the cell
      cycle.

PMID- 20807116
TI  - Some observations on the effects of bioprocessing on biopolymer stability.
AB  - A short review is given of some of the effects of the stresses encountered during
      bioprocessing of protein and carbohydrate-based macromolecular systems. This is
      of relevance to the effectiveness and safety of protein or peptide drugs
      themselves (such as insulin and monoclonal antibodies) and for the integrity of
      delivery systems (such as various carbohydrate-based hydrogel or mucoadhesive
      polymers). Some carbohydrate polymers are themselves bioactive or
      immunostimulatory and particular use is being made of polysaccharide and
      glycoconjugate vaccines whose effectiveness can be severely effected by chain
      degradation. Stability criteria include molecular weight and conformation and
      techniques ranging from simple viscomery measurements to sophisticated analytical
      ultracentrifuge and multi-angle light scattering coupled to size exclusion
      chromatography and precision viscometry measurements have been useful in this
      regard. We focus on some recent work on the degradation and aggregation of
      immunoglobulin G4-based monoclonal antibodies in response to repeated freezing
      and thawing and long-term storage, looking at the possible connection between
      conformation change and aggregation, the effects of storage conditions on the
      stability of chitosan mucoadhesive systems used for nasal and oral delivery. We
      look at the effects of sterilization conditions (thermal and irradiation) on the
      stability of a variety of other polysaccharides such as starches, kappa
      carrageenan, carboxymethylcellulose, alginate, low- and high-methoxy pectins,
      guar, and xyloglucans and consider the use of a relatively new method for the
      evaluation of the molecular weight distribution of glycoconjugate vaccines with
      molecular weights as high as 100 * 10(6) g/mol.

PMID- 20807117
TI  - Effects of a short burst of gait training with body weight-supported treadmill
      training for a person with chronic stroke: a single-subject study.
AB  - The purpose of this study was to investigate the effects of a short-burst dose of
      intense gait training with body weight-supported treadmill training (BWSTT) on
      walking speed, endurance, and quality of life of a participant with chronic
      stroke. A single-subject experimental (A-B-A-A) design with immediate and 3-month
      retention phases was used. The participant was a 66-year-old woman, 1 year after
      left cerebrovascular accident. Repeated baseline walking performance was
      established during 2 weeks of testing using the comfortable 10-meter walk test
      (CWT) and the 6-minute walk test (6MWT). The Stroke Impact Scale (SIS) was
      measured one time during baseline. Baseline testing was followed by ten 30-minute
      sessions of BWSTT over a 2-week duration. Retention testing was conducted
      immediately and 3 months following the intervention. Statistically significant
      improvements from baseline with the CWT and the 6MWT were achieved and maintained
      by the participant across all subsequent measurement phases. Improvements
      considered to be clinically meaningful changes in the SIS domains of strength and
      mobility achieved immediately after the intervention were not maintained at 3
      month retention testing. For the participant in this study, the short-burst
      dosage of BWSTT provided a feasible and effective means for improving goal
      oriented functional walking ability.

PMID- 20807115
TI  - The Fanconi anemia pathway and ICL repair: implications for cancer therapy.
AB  - Fanconi anemia (FA) is an inherited disease caused by mutations in at least 13
      genes and characterized by genomic instability. In addition to displaying
      strikingly heterogenous clinical phenotypes, FA patients are exquisitely
      sensitive to treatments with crosslinking agents that create interstrand
      crosslinks (ICL). In contrast to bacteria and yeast, in which ICLs are repaired
      through replication-dependent and -independent mechanisms, it is thought that
      ICLs are repaired primarily during DNA replication in vertebrates. However,
      recent data indicate that replication-independent ICL repair also operates in
      vertebrates. While the precise role of the FA pathway in ICL repair remains
      elusive, increasing evidence suggests that FA proteins function at different
      steps in the sensing, recognition and processing of ICLs, as well as in signaling
      from these very toxic lesions, which can be generated by a wide variety of cancer
      chemotherapeutic drugs. Here, we discuss some of the recent findings that have
      shed light on the role of the FA pathway in ICL repair, with special emphasis on
      the implications of these findings for cancer therapy since disruption of FA
      genes have been associated with cancer predisposition.

PMID- 20807118
TI  - Use of insulin pumps in India: suggested guidelines based on experience and
      cultural differences.
AB  - All type 1 diabetes mellitus (T1DM) subjects and the majority of type 2 diabetes
      mellitus (T2DM) subjects at one time or another require insulin to sustain life.
      Syringes and pens are presently the most popular insulin delivery devices. Though
      in use for more than 3 decades, insulin pumps are now being more commonly used
      because of their unique ability to continuously infuse insulin, closely mimicking
      that of physiological secretion from a normal pancreas. Unlike insulin shots with
      syringes, pump infusion sites need to be changed less frequently. Scientific
      evidence from published studies have proven added benefit of insulin pumps in
      improving quality of life, normalizing sugars in recalcitrant diabetes, improving
      sexual function, and relieving the intractable pain of neuropathy. In the western
      world, pumps are commonly used with T1DM subjects, whereas in India 80% of
      pumpers are T2DM subjects. The success of insulin pump therapy depends on
      selection of the right candidate, extensive education, motivation, and
      implementing the sophisticated programs with skill. However, all affordable
      patients are not ideal candidates for pump therapy because for successful
      continuation of pump therapy other inclusion criteria should also be fulfilled.
      Among the other indications discussed are a high level of insulin resistance,
      brittle diabetes, chronic kidney disease on renal replacement therapy, and
      continuous glucose monitoring pattern strongly suggesting need for a variable
      basal insulin infusion rate. In International Diabetes Foundation data released
      in 2009, estimated diabetes prevalence for 2010 is 285 million, representing 6.4%
      of the world's adult population, with a prediction that by 2030 the number of
      people with diabetes will have increased to 438 million. Considering this massive
      growth in T2DM and its propensity after 10-15 years to lead to an insulin
      deficient state, available evidence from studies is a compelling indication not
      to deny the benefits of continuous subcutaneous insulin infusion in selected T2DM
      subjects. This article aims at suggesting guidelines based on clinical experience
      and cultural diversity for India and developing countries.

PMID- 20807119
TI  - Effective intervention or child's play? A review of video games for diabetes
      education.
AB  - BACKGROUND: The purpose of this study is (1) to identify diabetes education video
      games and pilot studies in the literature, (2) to review themes in diabetes video
      game design and evaluation, and (3) to evaluate the potential role of educational
      video games in diabetes self-management education. METHODS: Studies were
      systematically identified for inclusion from Medline, Web of Science, CINAHL,
      EMBASE, Psychinfo, IEEE Xplore, and ACM Digital Library. Features of each video
      game intervention were reviewed and coded based on an existing taxonomy of
      diabetes interventions framework. RESULTS: Nine studies featuring 11 video games
      for diabetes care were identified. Video games for diabetes have typically
      targeted children with type 1 diabetes mellitus and used situation problem
      solving methods to teach diet, exercise, self-monitored blood glucose, and
      medication adherence. Evaluations have shown positive outcomes in knowledge,
      disease management adherence, and clinical outcomes. CONCLUSIONS: Video games for
      diabetes education show potential as effective educational interventions. Yet we
      found that improvements are needed in expanding the target audience, tailoring
      the intervention, and using theoretical frameworks. In the future, the reach and
      effectiveness of educational video games for diabetes education could be improved
      by expanding the target audience beyond juvenile type 1 diabetes mellitus, the
      use of tailoring, and increased use of theoretical frameworks.

PMID- 20807120
TI  - Continuous glucose monitoring reveals delayed nocturnal hypoglycemia after
      intermittent high-intensity exercise in nontrained patients with type 1 diabetes.
AB  - OBJECTIVE: Exercise is a cornerstone of diabetes therapy in type 1 diabetes
      mellitus (DMT1) patients. The type of exercise is important in determining the
      propensity to hypoglycemia. We assessed, by continuous glucose monitoring (CGM),
      the glucose profiles during and in the following 20h after a session of two
      different types of exercise. RESEARCH DESIGN AND METHODS: Eight male volunteers
      with well-controlled DMT1 were studied. They underwent 30min of both intermittent
      high-intensity exercise (IHE) and moderate-intensity exercise (MOD) in random
      order. Expired air was recorded during exercise, while metabolic and hormonal
      determinations were performed before and for 120 min after exercises. The CGM
      system and activity monitor were applied for the subsequent 20h. RESULTS: Blood
      glucose level declined during both type of exercise. At 150 min following the
      start of exercise, plasma glucose content was slightly higher after IHE. No
      changes were observed in plasma insulin concentration. A significant increase of
      norepinephrine concentration was noticed during IHE. Between midnight and 6:00
      a.m. the glucose levels were significantly lower after IHE than those observed
      after MOD (area under the curve, 23.3 +/- 3 vs. 16 +/- 3 mg/dL/420 min [P =
      0.04]; mean glycemia at 3 a.m., 225 +/- 31 vs. 147 +/- 17 mg/dL [P<0.05]). The
      number of hypoglycemic episodes after IHE was higher than that observed after MOD
      (seven vs. two [P<0.05]). CONCLUSIONS: We demonstrate that (1) CGM is a useful
      approach in DMT1 patients who undergo an exercise program and (2) IHE is
      associated with delayed nocturnal hypoglycemia.

PMID- 20807122
TI  - Long road ahead to change veterinary education.

PMID- 20807123
TI  - Clarification on drugs used to treat leishmaniasis.

PMID- 20807124
TI  - What is your diagnosis? Disruption in the quadriceps apparatus.

PMID- 20807125
TI  - What is your diagnosis? Abdominal wall hernia involving the urinary bladder.

PMID- 20807126
TI  - Pathology in practice. Hypertrophy of the tunica muscularis.

PMID- 20807127
TI  - ECG of the month. Sinus bradycardia.

PMID- 20807128
TI  - Referring veterinarians' opinions and veterinary teaching hospital veterinarians'
      perceptions of those opinions regarding communication and nutritional product
      recommendations.
AB  - OBJECTIVE: To compare opinions of referring veterinarians and perceptions of
      veterinary teaching hospital (VTH) veterinarians of those opinions regarding
      nutritional product recommendations made by VTH veterinarians. DESIGN: Survey.
      SAMPLE POPULATION: VTH veterinarians from 10 US colleges of veterinary medicine
      and referring veterinarians within a 160-km (100-mile) radius of each of those
      colleges. PROCEDURES: Questions intended to assess the attitudes of VTH
      clinicians and referring veterinarians toward recommendations on nutritional
      products were designed by use of item statements with a 7-point Likert scale.
      Data were evaluated by use of crosstab analysis and Likert bipolar scaling to
      measure overall positive or negative responses to statements and to determine
      significant differences in responses to demographic and communication questions.
      RESULTS: Referring veterinarians returned 1,430 of 12,720 surveys, and VTH
      veterinarians returned 98 of 690 surveys (response rate, 11.2% and 14.2%,
      respectively). Significant communication gaps between general practitioners and
      board-certified veterinarians existed. The VTH veterinarians consistently
      reported providing written case summaries sooner than referring veterinarians
      reported receiving them. Referring veterinarians indicated that they expected and
      welcomed specific nutritional recommendations more than was perceived by VTH
      veterinarians. CONCLUSIONS AND CLINICAL RELEVANCE: VTH veterinarians should not
      assume the attitudes of referring veterinarians, particularly with regard to
      specific nutritional recommendations. Failure to discuss specific nutritional
      recommendations may prevent effective consultation between veterinarians and also
      may directly affect clients who may experience delays in treatment for their
      pets. Procedural issues related to delivery and receipt of written case summaries
      should be investigated by VTH veterinarians and general practitioners.

PMID- 20807129
TI  - Recognition of the threat of Ehrlichia ruminantium infection in domestic and wild
      ruminants in the continental United States.

PMID- 20807130
TI  - Evaluation of the relationship between Orthopedic Foundation for Animals' hip
      joint scores and PennHIP distraction index values in dogs.
AB  - OBJECTIVE: To compare 2 screening methods for detecting evidence of hip dysplasia
      (Orthopedic Foundation for Animals [OFA] and PennHIP) in dogs. DESIGN: Diagnostic
      test evaluation study. Animals-439 dogs >or= 24 months of age that received
      routine hip joint screening from June 1987 through July 2008. PROCEDURES: Dogs
      were sedated, and PennHIP radiography was performed (hip joint- extended [HE],
      compression, and distraction radiographic views). The HE radiographic view was
      submitted for OFA evaluation. A copy of the HE radiographic view plus the
      compression and distraction radiographic views were submitted for routine PennHIP
      evaluation, including quantification of hip joint laxity via the distraction
      index (DI). RESULTS: 14% (60/439) of dogs had hip joints scored as excellent by
      OFA standards; however, 52% (31/60) of those had a DI >or= 0.30 (range, 0.14 to
      0.61). Eighty-two percent of (183/223) dogs with OFA-rated good hip joints had a
      DI >or= 0.30 (range, 0.10 to 0.77), and 94% (79/84) of dogs with OFA-rated fair
      hip joints had a DI >or= 0.30 (range, 0.14 to 0.77). Of all dogs with fair to
      excellent hip joints by OFA standards, 80% (293/367) had a DI >or= 0.30. All dogs
      with OFA-rated borderline hip joints or mild, moderate, or severe hip dysplasia
      had a DI >or= 0.30 (range, 0.30 to 0.83). CONCLUSION AND CLINICAL RELEVANCE: Dogs
      judged as phenotypically normal by the OFA harbored clinically important passive
      hip joint laxity as determined via distraction radiography. Results suggested
      that OFA scoring of HE radiographs underestimated susceptibility to
      osteoarthritis in dogs, which may impede progress in reducing or eliminating hip
      dysplasia through breeding.

PMID- 20807131
TI  - Developmental uterine anomalies in cats and dogs undergoing elective
      ovariohysterectomy.
AB  - OBJECTIVE: To describe the characteristics and frequency of gross uterine
      anomalies in cats and dogs undergoing elective ovariohysterectomy. DESIGN:
      Prospective and retrospective case series. ANIMALS: 53,258 cats and 32,660 dogs
      undergoing elective ovariohysterectomy at 26 clinics in the United States and
      Canada during 2007. PROCEDURES: Clinics prospectively reported gross anomalies
      and submitted tissues from abnormal reproductive tracts identified during
      surgery. Records from a feral cat spay-neuter clinic were evaluated
      retrospectively. RESULTS: Suspected congenital anomalies of the uterus were
      identified in 0.09% (49/53,258) of female cats and 0.05% (15/32,660) of female
      dogs. Uterine anomalies identified included unicornuate uterus (33 cats and 11
      dogs), segmental agenesis of 1 uterine horn (15 cats and 3 dogs), and uterine
      horn hypoplasia (1 cat and 1 dog). Ipsilateral renal agenesis was present in
      29.4% (10/34) of cats and 50.0% (6/12) of dogs with uterine anomalies in which
      kidneys were evaluated. Mummified ectopic fetuses were identified in 4 cats with
      uterine anomalies. Both ovaries and both uterine tubes were present in most
      animals with uterine anomalies. CONCLUSIONS AND CLINICAL RELEVANCE: Urogenital
      anomalies were twice as common in cats as in dogs. Identification of uterine
      developmental anomalies in dogs and cats should trigger evaluation of both
      kidneys and both ovaries because ipsilateral renal agenesis is common, but both
      ovaries are likely to be present and should be removed during ovariohysterectomy.

PMID- 20807132
TI  - Barium toxicosis in a dog.
AB  - CASE DESCRIPTION: A 2-year-old 14.9-kg (32.8-lb) neutered female Shetland
      Sheepdog was admitted to the University of Liverpool Small Animal Teaching
      Hospital for evaluation of acute collapse. CLINICAL FINDINGS: At admission, the
      dog was tachypneic and had reduced limb reflexes and muscle tone in all limbs
      consistent with diffuse lower motor neuron dysfunction. The dog was severely
      hypokalemic (1.7 mEq/L; reference range, 3.5 to 5.8 mEq/L). Clinical status of
      the dog deteriorated; there was muscle twitching, flaccid paralysis, and
      respiratory failure, which was considered a result of respiratory muscle
      weakness. Ventricular arrhythmias and severe acidemia (pH, 7.18; reference range,
      7.35 to 7.45) developed. Intoxication was suspected, and plasma and urine samples
      submitted for barium analysis had barium concentrations comparable with those
      reported in humans with barium toxicosis. Analysis of barium concentrations in 5
      control dogs supported the diagnosis of barium toxicosis in the dog. TREATMENT
      AND OUTCOME: Fluids and potassium supplementation were administered IV. The dog
      recovered rapidly. Electrolyte concentrations measured after recovery were
      consistently unremarkable. Quantification of plasma barium concentration 56 days
      after the presumed episode of intoxication revealed a large decrease; however,
      the plasma barium concentration remained elevated, compared with that in control
      dogs. CLINICAL RELEVANCE: To our knowledge, this case represented the first
      description of barium toxicosis in the veterinary literature. Barium toxicosis
      can cause life-threatening hypokalemia; however, prompt supportive treatment can
      yield excellent outcomes. Barium toxicosis is a rare but important differential
      diagnosis in animals with hypokalemia and appropriate clinical signs.

PMID- 20807133
TI  - Thoracoscopic subtotal pericardiectomy and right atrial mass resection in a dog.
AB  - CASE DESCRIPTION: A 10-year-old spayed female Corgi mix was examined for a 3-week
      history of lethargy and weight gain. CLINICAL FINDINGS: Physical examination
      findings included muffled heart sounds and a distended abdomen with a fluid wave
      on ballottement. Thoracic radiography revealed a globoid cardiac silhouette, and
      thoracic ultrasonography indicated pericardial effusion and a pedunculated mass
      originating from the right auricle. TREATMENT AND OUTCOME: Initial treatment
      consisted of pericardiocentesis. One week later, thoracoscopic right atrial mass
      resection was performed. No surgical complications were noted, and the dog was
      discharged approximately 28 hours after surgery. Results of histologic
      examination of the mass indicated a grade 2 hemangiosarcoma with incomplete
      margins. Treatment with doxorubicin was initiated 35 days after surgery. The dog
      survived for 177 days after mass resection, when it was euthanized because of
      complications related to metastatic disease. CLINICAL RELEVANCE: Findings
      suggested that thoracoscopic right atrial mass removal combined with adjunct
      doxorubicin treatment may be a viable alternative to thoracotomy in dogs with
      right atrial masses.

PMID- 20807134
TI  - Clinical, histologic, and bacteriologic findings in dairy cows with digital
      dermatitis (footwarts) one month after topical treatment with lincomycin
      hydrochloride or oxytetracycline hydrochloride.
AB  - OBJECTIVE: To compare the effectiveness of lincomycin and oxytetracycline for
      treatment of digital dermatitis (DD) in dairy cows through gross visual
      examination, histologic evaluation, and bacteriologic evaluation. DESIGN:
      Randomized controlled clinical trial. ANIMALS: 25 cows with DD lesions from a
      commercial Holstein dairy herd. PROCEDURES: Cows with DD lesions were randomly
      assigned to 1 of 3 groups: topical treatment with 10 g of lincomycin
      hydrochloride (n = 11), topical treatment with 10 g of oxytetracycline
      hydrochloride (11), and no treatment (3) on days 1 and 2 (d1). Biopsy specimens
      were obtained for histologic examination from DD lesions prior to treatment and
      28 or 31 days (d30) after treatment for histologic examination. Cows were
      clinically examined on d1, days 12 or 14 (d14), and d30. RESULTS: No difference
      was evident in clinical responses to lincomycin and oxytetracycline, so data were
      pooled; at d30, 8 of 11 of lincomycin-treated lesions and 7 of 11 oxytetracycline
      treated lesions appeared visually healed, respectively. Gross visual examination
      suggested 73% (16/22) of treated cows were healed at d14 and 68% (15/22) of
      treated cows were healed on d30. Of the 15 lesions that appeared healed on d30, 7
      of 15 were classified histologically as active (ulceration and bacterial
      invasion; 2/15) or incipient (5/15). CONCLUSIONS AND CLINICAL RELEVANCE: Clinical
      responses to lincomycin and oxytetracycline did not differ. Agreement was good
      between gross visual and histologic assessments of DD lesions before treatment;
      agreement 1 month after treatment was variable. Histologic evaluation could not
      distinguish incomplete healing from lesion recurrence.

PMID- 20807135
TI  - Reference intervals and relationships between health status, carapace length,
      body mass, and water temperature and concentrations of plasma total protein and
      protein electrophoretogram fractions in Atlantic loggerhead sea turtles and green
      turtles.
AB  - OBJECTIVE: To determine reference intervals for concentrations of plasma total
      protein (TP) and electrophoretogram fractions (ELFs) for healthy, wild loggerhead
      sea turtles (Caretta caretta) and green turtles (Chelonia mydas) and to assess
      relationships between TP and ELF concentrations and health status, body size,
      body mass, and water temperature. DESIGN: Evaluation study. ANIMALS: 437 healthy
      and 35 ill Atlantic loggerhead sea turtles and 152 healthy and 3 ill Atlantic
      green turtles. PROCEDURES: Free-ranging turtles were captured from a nuclear
      power plant intake canal in southern Florida. Plasma samples were obtained from
      all turtles. Plasma TP and ELF concentrations were measured, and reference
      intervals were calculated. Wilcoxon rank-sum tests were used to compare TP and
      ELF values between healthy and ill loggerhead sea turtles. Spearman rank
      correlations were evaluated between concentrations of TP and ELFs and carapace
      length, body mass, and water temperature. RESULTS: Reference intervals for TP
      concentrations were 2.2 to 5.2 g/dL and 2.0 to 5.4 g/dL for loggerhead sea
      turtles and green turtles, respectively. Except for gamma-globulin,
      concentrations of ELFs were significantly higher in healthy than in ill
      loggerhead sea turtles. There was a positive correlation between TP, alpha
      globulin, beta-globulin, and gamma-globulin concentrations and water temperature
      in loggerhead sea turtles and between only TP and alpha-globulin concentrations
      and water temperature in green turtles. CONCLUSIONS AND CLINICAL RELEVANCE:
      Reference intervals for concentrations of TP and ELFs for healthy, free-ranging
      loggerhead sea turtles and green turtles can be used in combination with other
      diagnostic tools to assess health status of sea turtles.

PMID- 20807138
TI  - Three-dimensional biomechanics of simulated laryngeal abduction in horses.
AB  - OBJECTIVE: To investigate the influence of simulated contraction of the
      cricoarytenoideus dorsalis (CAD) muscle on the 3-D motion of the arytenoid
      cartilage. SAMPLE POPULATION: 5 larynges from equine cadavers. PROCEDURES: Serial
      computed tomographic scans of each larynx were conducted at 7 incremental forces
      simulating contraction of medial, lateral, and combined bellies of the left CAD
      muscle. Three-dimensional reconstruction of radiopaque markers placed at anatomic
      landmarks on the left arytenoid and cricoid cartilages enabled quantification of
      marker displacement according to a Cartesian coordinate system. Rotation (roll,
      pitch, and yaw) of dorsal and ventral arytenoid planes was calculated relative to
      a plane formed by the coordinates of 3 markers on the cricoid cartilage by use of
      Euler angles. RESULTS: Displacement and rotational data showed that rocking
      motion occurs throughout arytenoid abduction and most of the rotational component
      is attributable to pitch; greater pitch was associated with action of the lateral
      belly. Roll of the ventral arytenoid plane was principally associated with action
      of the medial belly, which counteracted the tendency of the arytenoid cartilage
      to rotate medially into the rima glottidis lumen. The distance between markers on
      the arytenoid cartilage was not constant during contraction because of slight
      deformation of the corniculate process of the arytenoid cartilage, therefore
      indicating that the arytenoid cartilage is not a rigid body during abduction.
      CONCLUSIONS AND CLINICAL RELEVANCE: Arytenoid cartilage abduction was dependent
      on the rocking motion elicited by the lateral belly of the CAD muscle; therefore,
      laryngoplasty suture placement should mimic the action of the lateral, rather
      than the medial, muscle belly.

PMID- 20807137
TI  - Temporal-spatial gait analysis by use of a portable walkway system in healthy
      Labrador Retrievers at a walk.
AB  - OBJECTIVE: To establish a protocol to collect temporal-spatial gait analysis
      variables by use of a portable walkway system in Labrador Retrievers at a walk
      and to determine reference values. ANIMALS: 56 healthy Labrador Retrievers.
      PROCEDURES: 6 passes across the walkway (3 passes in each direction) were
      recorded. Inclusion criteria for a pass were that the dog was at a walk
      (velocity, 60.0 to 90.0 cm/s) and had minimal head turning. The first 3 passes
      that met the inclusion criteria were analyzed for each dog. RESULTS: Mean stride
      length was 88.4 cm. Mean stance time (ST) of forelimbs and hind limbs was 0.62
      and 0.56 seconds, respectively. Mean stance time percentage (ST%; proportion of
      stance time to total gait cycle time) for forelimbs and hind limbs was 55.6% and
      50.2%, respectively. Mean total pressure index (TPI) of forelimbs and hind limbs
      was 27.1 and 17.4, respectively. Mean number of sensors (NS) activated by each
      paw strike of forelimbs and hind limbs was 17 and 13, respectively. Mean forelimb
      to-hind limb symmetry ratios were 1.11 (ST), 1.10 (ST%), 1.62 (TPI), and 1.37
      (NS). Symmetry ratios for left limbs to right limbs, left forelimb to right
      forelimb, and left hind limb to right hind limb were 1.00. CONCLUSIONS AND
      CLINICAL RELEVANCE: A protocol for collection of temporal-spatial gait analysis
      variables with a portable walkway system in Labrador Retrievers at a walk was
      developed, and reference values for variables and symmetry ratios were reported.
      Further research will determine the extent to which symmetry ratios differ in
      dogs with orthopedic disorders.

PMID- 20807139
TI  - Effects of hypercapnia, hypocapnia, and hyperoxemia on brain morphometrics
      determined by use of T1-weighted magnetic resonance imaging in isoflurane
      anesthetized dogs.
AB  - OBJECTIVE: To evaluate the effects of various combinations of PaCO2 and PaO2
      values on brain morphometrics. ANIMALS: 6 healthy adult dogs. PROCEDURES: A
      modified Latin square design for randomization was used. Dogs were anesthetized
      with propofol (6 to 8 mg/kg, IV), and anesthesia was maintained with isoflurane
      (1.7%) and atracurium (0.2 mg/kg, IV, q 30 min). Three targeted values of PaCO2
      (20, 40, and 80 mm Hg) and 2 values of PaO2 (100 and 500 mm Hg) were achieved in
      each dog, yielding 6 combinations during a single magnetic resonance (MR) imaging
      session. When the endpoints were reached, dogs were given at least 5 minutes for
      physiologic variables to stabilize before T1-weighted MR images were obtained.
      Total brain volume (TBV) and lateral ventricular volume (LVV) were calculated
      from manually drawn contours of areas of interest by use of a software program,
      with each dog serving as its own control animal. Three blinded investigators
      subjectively evaluated the lateral ventricular size (LVS) and the cerebral sulci
      width (CSW). Brain morphometric values were compared among the target blood gas
      states. RESULTS: No significant differences in TBV were found among target
      states. The LVV was significantly greater during hypocapnia, compared with
      hypercapnia at the same PaO2 value. With regard to the subjective evaluations,
      there were no significant differences among evaluators or among combinations of
      PaO2 and PaCO2 values. CONCLUSIONS AND CLINICAL RELEVANCE: The changes observed
      in LVV during hypocapnia and hypercapnia may serve as a potential confounding
      factor when neuromorphometric evaluations are performed in anesthetized dogs.

PMID- 20807140
TI  - Comparison of the effects of tramadol, codeine, and ketoprofen alone or in
      combination on postoperative pain and on concentrations of blood glucose, serum
      cortisol, and serum interleukin-6 in dogs undergoing maxillectomy or
      mandibulectomy.
AB  - OBJECTIVE: To compare analgesic effects of tramadol, codeine, and ketoprofen
      administered alone and in combination and their effects on concentrations of
      blood glucose, serum cortisol, and serum interleukin (IL)-6 in dogs undergoing
      maxillectomy or mandibulectomy. ANIMALS: 42 dogs with oral neoplasms. PROCEDURES:
      30 minutes before the end of surgery, dogs received SC injections of tramadol (2
      mg/kg), codeine (2 mg/kg), ketoprofen (2 mg/kg), tramadol+ketoprofen, or
      codeine+ketoprofen (at the aforementioned dosages). Physiologic variables,
      analgesia, and sedation were measured before (baseline) and 1, 2, 3, 4, 5, and 24
      hours after surgery. Blood glucose, serum cortisol, and serum IL-6 concentrations
      were measured 1, 3, 5, and 24 hours after administration of analgesics. RESULTS:
      All treatments provided adequate postoperative analgesia. Significant increases
      in mean+/-SD blood glucose concentrations were detected in dogs receiving
      tramadol (96+/-14 mg/dL), codeine (120+/-66 mg/dL and 96+/-21 mg/dL), ketoprofen
      (105+/-22 mg/dL), and codeine+ketoprofen (104+/-16 mg/dL) at 5, 1 and 3, 5, and 3
      hours after analgesic administration, respectively, compared with preoperative
      (baseline) values. There were no significant changes in physiologic variables,
      serum IL-6 concentrations, or serum cortisol concentrations. Dogs administered
      codeine+ketoprofen had light but significant sedation at 4, 5, and 24 hours.
      CONCLUSIONS AND CLINICAL RELEVANCE: Opioids alone or in combination with an NSAID
      promoted analgesia without adverse effects during the 24-hour postoperative
      period in dogs undergoing maxillectomy or mandibulectomy for removal of oral
      neoplasms.

PMID- 20807141
TI  - Thermal antinociceptive effect of orally administered gabapentin in healthy cats.
AB  - OBJECTIVE: To determine the thermal antinociceptive effect of various single
      doses of gabapentin administered orally in cats. ANIMALS: 6 healthy adult
      domestic shorthair cats. PROCEDURES: Baseline skin temperature and baseline
      thermal threshold were determined via application of a thermal probe to the
      thorax of each cat prior to oral administration (in random order) of an empty
      capsule (placebo) or a capsule containing 5, 10, or 30 mg of gabapentin/kg (4
      experiments/cat). After each treatment, thermal threshold was determined at
      intervals during an 8-hour period. Plasma gabapentin concentration was measured
      prior to and at 1-hour intervals after drug administration. Dose and time effects
      were analyzed by use of a repeated-measures ANOVA. RESULTS: Peak plasma
      gabapentin concentration increased with increasing gabapentin dose. After
      administration of the 5, 10, and 30 mg/kg doses, median interval until the
      greatest gabapentin concentration was detected was 60, 120, and 90 minutes,
      respectively (interval ranges were 60 to 120 minutes, 60 to 120 minutes, and 60
      to 180 minutes, respectively). In the experiments involving administration of the
      placebo or increasing doses of gabapentin, mean+/-SD baseline skin temperature
      and thermal threshold were 36.8+/-1.21 degrees C and 45.8+/-4.4 degrees C, 36.9+/
      1.1 degrees C and 43.1+/-2.4 degrees C, 37.0+/-0.7 degrees C and 44.0+/-1.5
      degrees C, and 36.1+/-1.7 degrees C and 43.3+/-3.3 degrees C, respectively. There
      was no significant effect of treatment on thermal threshold. CONCLUSIONS AND
      CLINICAL RELEVANCE: At the doses evaluated, orally administered gabapentin did
      not affect the thermal threshold in healthy cats and therefore did not appear to
      provide thermal antinociception.

PMID- 20807142
TI  - Erythrocyte survival time in Greyhounds as assessed by use of in vivo
      biotinylation.
AB  - OBJECTIVE: To determine erythrocyte survival time in Greyhounds. ANIMALS: 6
      Greyhounds used as blood donors and 3 privately owned non-Greyhound dogs.
      PROCEDURES: In vivo biotinylation of erythrocytes was performed by infusion of
      biotin-N-hydroxysuccinimide into each dog via a jugular vein catheter. Blood
      samples were collected 12 hours later and then at weekly intervals and were used
      to determine the percentage of biotin-labeled erythrocytes at each time point.
      Erythrocytes were washed, incubated with avidin-fluorescein isothiocyanate, and
      washed again before the percentage of biotinylated erythrocytes was measured by
      use of flow cytometry. Survival curves for the percentage of biotinylated
      erythrocytes were generated, and erythrocyte survival time was defined as the x
      intercept of a least squares best-fit line for the linear portion of each curve.
      RESULTS: The R2 for survival curves ranged from 0.93 to 0.99 during the first 10
      weeks after infusion of erythrocytes. Erythrocyte survival time for the 3 non
      Greyhound dogs was 94, 98, and 116 days, respectively, which was consistent with
      previously reported values. Erythrocyte survival time for the 6 Greyhounds ranged
      from 83 to 110 days (mean, 93 days; median, 88 days). As determined by use of in
      vivo biotinylation, erythrocyte survival times in Greyhounds were similar to
      those determined for non-Greyhound dogs and did not differ significantly from
      erythrocyte survival times reported previously for non-Greyhound dogs.
      CONCLUSIONS AND CLINICAL RELEVANCE: Erythrocyte survival time was similar in
      Greyhounds and non-Greyhound dogs. Greyhounds can be used as erythrocyte donors
      without concerns about inherently shorter erythrocyte survival time.

PMID- 20807143
TI  - Effects of consuming diets containing various fats or citrus flavanones on plasma
      lipid and urinary F2-isoprostane concentrations in overweight cats.
AB  - OBJECTIVE: To compare in overweight cats the effects of feeding moderate-energy
      diets with moderate fat content but with saturated fat (beef tallow), saturated
      fat plus citrus flavanones, or monounsaturated fat (olive oil) on plasma lipids
      and urinary F2-isoprostane concentrations. ANIMALS: 20 overweight cats with
      mean+/-SD body weight of 5.2+/-0.2 kg and mean body condition score of 7.8+/-0.2
      (9-point scale). PROCEDURES: Body weight, plasma total cholesterol and
      triacylglycerol concentrations, and urinary F2-isoprostane concentration (as
      marker of oxidative stress) were measured at the beginning of the study, when the
      cats were fed a maintenance diet, and after 1, 3, and 5 months of consuming test
      diets. RESULTS: In overweight cats, citrus flavanones supplementation of the
      saturated fat diet was associated with lower energy intake and with lower plasma
      lipids and urinary F2-isoprostane concentrations than in cats fed the saturated
      fat alone. Monounsaturated fat feeding resulted in lower food intake than in cats
      fed saturated fat. However, plasma lipids concentrations remained within
      reference limits throughout the study. CONCLUSIONS AND CLINICAL RELEVANCE:
      Although the clinical relevance of these findings is unknown, the significant
      differences detected indicated that lower energy intake with citrus flavanones
      supplementation or with substitution of saturated fat for monounsaturated fat
      could be good strategies for decreasing plasma lipids concentration and oxidative
      stress in overweight cats, even before considerable loss of body weight is
      observed.

PMID- 20807144
TI  - Risk factors for the incidence of calcium oxalate uroliths or magnesium ammonium
      phosphate uroliths for dogs in Ontario, Canada, from 1998 to 2006.
AB  - OBJECTIVE: To investigate individual- and community-level contextual variables as
      risk factors for submission of calcium oxalate (CaOx) uroliths or magnesium
      ammonium phosphate (ie, struvite) uroliths for dogs to a national urolith center,
      as determined on the basis of urolith submission patterns. SAMPLE POPULATION:
      Records of 7,297 dogs from Ontario, Canada, with CaOx or struvite uroliths
      submitted to the Canadian Veterinary Urolith Centre from 1998 through 2006.
      PROCEDURES: Data were analyzed via multilevel multivariable logistic regression.
      RESULTS: Individual-level main effects and interactions significantly associated
      with the risk of submission of CaOx uroliths rather than struvite uroliths
      included age, sex, breed group, neuter status, body condition, dietary moisture
      content, diet type, sex-neuter status interaction, sex-age interaction, body
      condition-age interaction, and breed group-dietary moisture content interaction.
      In addition, median community family income and being located within a major
      urban center (ie, Toronto) were significant risk factors for submission of CaOx
      uroliths, compared with submission of struvite uroliths. CONCLUSIONS AND CLINICAL
      RELEVANCE: Individual-level and dietary factors for dogs affected the risk of
      submission of CaOx uroliths, relative to that of struvite uroliths. Interactions
      among these variables need to be considered when assessing the impact of these
      risk factors. In addition, community-level or contextual factors (such as
      community family income and residing in a densely populated area of Ontario) also
      affected submission patterns, although most of the variance in the risk for
      submission of CaOx uroliths, compared with the risk for submission of struvite
      uroliths, was explained by individual-level factors.

PMID- 20807145
TI  - Effects of topical administration of latanoprost, timolol, or a combination of
      latanoprost and timolol on intraocular pressure, pupil size, and heart rate in
      clinically normal dogs.
AB  - OBJECTIVE: To determine effects after topical administration of latanoprost,
      timolol, or a commercially available latanoprosttimolol combination twice daily
      on intraocular pressure (IOP), pupil size (PS), and heart rate (HR) in clinically
      normal dogs. ANIMALS: 17 clinically normal dogs. PROCEDURES: A randomized
      controlled clinical trial was performed with a treatment (n=9) and saline (0.9%
      NaCl) solution group (8). Each dog in the treatment group received 3 treatments
      (latanoprost, timolol, and the latanoprost-timolol combination), with a 14-day
      washout period between treatments. Baseline values were established on day 1 of
      each treatment period. On days 2 through 5, drugs were administered topically
      every 12 hours to 1 eye of each dog in the treatment group. In both groups, IOP
      PS, and HR were measured at 0, 2, 4, 6, 8, and 9 hours on days 2 and 5. RESULTS:
      Eyes treated with latanoprost or the latanoprost-timolol combination had a
      significant decrease in IOP and a significantly smaller PS, compared with results
      for dogs receiving only timolol or dogs in the saline solution group. Timolol and
      the latanoprost-timolol combination both significantly lowered HR, compared with
      HR following administration of latanoprost and the saline solution. CONCLUSIONS
      AND CLINICAL RELEVANCE: Topical administration of latanoprost alone was as
      effective at lowering IOP as was administration of the latanoprost-timolol
      combination when both were given every 12 hours to clinically normal dogs.
      Timolol, either alone or in combination with latanoprost, appeared to have little
      or no effect on IOP in clinically normal dogs but was associated with a reduction
      in HR.

PMID- 20807146
TI  - Pharmacokinetics and tissue distribution of minocycline hydrochloride in horses.
AB  - OBJECTIVE: To determine the pharmacokinetics and tissue distribution of
      minocycline in horses. ANIMALS: 5 healthy Thoroughbred mares for the
      pharmacokinetic experiment and 6 healthy Thoroughbred mares for the tissue
      distribution experiment. PROCEDURES: Each mare was given 2.2 mg of minocycline
      hydrochloride/kg, IV. Blood samples were collected once before minocycline
      administration (0 hours) and 10 times within 48 hours after administration in the
      pharmacokinetics study, and 24 tissue samples were obtained at 0.5 and 3 hours in
      the distribution study. RESULTS: No adverse effects were observed in any of the
      mares after minocycline administration. The mean+/-SD elimination half-life was
      7.70+/-1.91 hours. The total body clearance was 0.16+/-0.04 L/h/kg, and the
      volume of distribution at steady state was 1.53+/-0.09 L/kg. The percentage of
      plasma protein binding was 68.1+/-2.6%. Plasma concentration of free minocycline
      was 0.12 microg/mL at 12 hours. Minocycline was not detected in brain tissue, CSF
      or aqueous humor at 0.5 hours; however, it was found in all tissues, except in
      the aqueous humor, at 3 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Clearance of
      minocycline in healthy mares was greater than that reported for humans. For
      effective treatment of infections with common equine pathogens, it will be
      necessary to administer minocycline at a dosage of 2.2 mg/kg, IV, every 12 hours.
      This drug could be useful for infections in many tissues, including the CNS. The
      pharmacokinetic and tissue distribution data should aid in the appropriate use of
      minocycline in horses.

PMID- 20807147
TI  - Effects of firocoxib, meloxicam, and tepoxalin administration on eicosanoid
      production in target tissues of healthy cats.
AB  - OBJECTIVE: To evaluate the effects of firocoxib, meloxicam, and tepoxalin
      administration in healthy cats by measuring the ability of stimulated tissues to
      synthesize eicosanoids ex vivo. ANIMALS: 8 healthy adult male cats. PROCEDURES:
      In a blinded, randomized, crossover study design, cats were treated with
      firocoxib (1 mg/kg, PO, q 24 h), meloxicam (0.05 mg/kg, PO, q 24 h), tepoxalin
      (5.0 mg/kg, PO, q 12 h), or a placebo for 8 days. Blood samples and gastric and
      duodenal mucosal biopsy specimens were collected on days 0 (baseline; immediately
      before treatment), 3, and 8 of each treatment period. Thromboxane B2 (TXB2)
      concentrations were measured in serum, and prostaglandin E2 (PGE2) and
      leukotriene B4 (LTB4) concentrations were measured in plasma. Prostaglandin E1
      (PGE1) synthesis, PGE2 synthesis, and LTB4 concentrations were measured in
      mucosal biopsy specimens. A 21-day minimum washout period was observed between
      treatments. Repeated-measures analyses were performed. RESULTS: Firocoxib and
      meloxicam administration resulted in a lower plasma PGE2 concentration than at
      baseline on days 3 and 8 of administration, whereas tepoxalin administration did
      not. Tepoxalin administration resulted in a lower serum TXB2 concentration and
      pyloric and duodenal PGE1 synthesis on both days, compared with baseline and
      placebo administration. Neither firocoxib nor meloxicam administration altered
      pyloric or duodenal PGE1 synthesis on either day, compared with placebo
      administration. Tepoxalin administration also resulted in lower pyloric mucosal
      LTB4 concentrations on both days, compared with baseline values. CONCLUSIONS AND
      CLINICAL RELEVANCE: Firocoxib and meloxicam administration had no effect on
      cyclooxygenase-1 activity, whereas tepoxalin administration resulted in
      inhibition of cyclooxygenase-1 and 5-lipoxygenase.

PMID- 20807149
TI  - Physiologic effects of nasopharyngeal administration of supplemental oxygen at
      various flow rates in healthy neonatal foals.
AB  - OBJECTIVE: To evaluate the effects of various flow rates of oxygen administered
      via 1 or 2 nasal cannulae on the fraction of inspired oxygen concentration (FIO2)
      and other arterial blood gas variables in healthy neonatal foals. ANIMALS: 9
      healthy neonatal (3- to 4-day-old) foals. PROCEDURES: In each foal, a nasal
      cannula was introduced into each naris and passed into the nasopharynx to the
      level of the medial canthus of each eye; oxygen was administered at 4 flow rates
      through either 1 or both cannulae (8 treatments/foal). Intratracheal FIO2,
      intratracheal end-tidal partial pressure of carbon dioxide, and arterial blood
      gas variables were measured before (baseline) and during unilateral and bilateral
      nasopharyngeal delivery of 50, 100, 150, and 200 mL of oxygen/kg/min. RESULTS: No
      adverse reactions were associated with administration of supplemental oxygen
      except at the highest flow rate, at which the foals became agitated. At
      individual flow rates, significant and dose-dependent increases in FIO2, PaO2,
      and oxygen saturation of hemoglobin (SaO2) were detected, compared with baseline
      values. Comparison of unilateral and bilateral delivery of oxygen at similar
      cumulative flow rates revealed no differences in evaluated variables. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results indicated that administration of supplemental
      oxygen via nasal cannulae appeared to be a highly effective means of increasing
      FIO2, PaO2, and SaO2 in neonatal foals. These findings may provide guidance for
      implementation of oxygen treatment in hypoxemic neonatal foals.

PMID- 20807148
TI  - Evaluation of the effect of bolus administration of 50% dextrose solution on
      measures of electrolyte and energy balance in postpartum dairy cows.
AB  - OBJECTIVE: To determine the effect of IV administration of a bolus of 50%
      dextrose solution on electrolyte and energy balance and effect of blood
      collection site on serum electrolyte values in postparturient dairy cows.
      ANIMALS: 24 clinically normal multiparous cows. PROCEDURES: A bolus of 50%
      dextrose solution (0.5 L [n=8 cows]), 50% dextrose solution (1.0 L [8]), or
      saline (0.9% NaCl) solution (1.0 L, control treatment [8]) was administered via
      jugular venipuncture 5 to 10 days after parturition. Pretreatment and
      posttreatment blood samples were analyzed for concentrations of calcium,
      magnesium, phosphorus, potassium, glucose, insulin, beta-hydroxybutyric acid
      (BHBA), and nonesterified fatty acids. Coccygeal vessel and jugular vein blood
      samples were obtained prior to treatment, and electrolyte concentrations were
      compared. RESULTS: Treatment with 50% dextrose decreased phosphorus concentration
      in serum, compared with the control treatment. Suppression of BHBA and
      nonesterified fatty acid concentrations following dextrose treatment lasted for
      <12 hours; mean BHBA concentrations in all groups were increased 24 hours after
      treatment. Mean serum phosphorus concentration in coccygeal vessel blood samples
      was 0.67 mg/dL greater than the concentration in jugular vein blood samples.
      CONCLUSIONS AND CLINICAL RELEVANCE: Postpartum cows treated with dextrose
      solution may be at risk for hypophosphatemia, and 1 treatment with 0.5 or 1 L of
      50% dextrose solution is unlikely to prevent or resolve acetonemia (ketosis). The
      risk of hypophosphatemia may be underestimated when coccygeal vessel blood
      samples are used for diagnosis.

PMID- 20807150
TI  - In vitro evaluation of a low-modulus mesh canine prosthetic hip stem.
AB  - OBJECTIVE: To compare an electron beam melting-processed (EBMP) low-modulus
      titanium alloy mesh stem with a commercial cobalt-chromium (CC) stem in a canine
      cadaver model. SAMPLE POPULATION: 9 pairs of cadaver femora. PROCEDURES: EBMP
      stems of 3 sizes were placed in randomly chosen sides of femora (left or right)
      and CC stems in opposite sides. Stem impaction distances were recorded. Five
      strain gauges were attached to the femoral surface to record transverse tensile
      (hoop) strains in the femur during axial loading. Constructs were axially loaded
      4 times to 800 N and 4 times to 1,600 N in a materials testing machine. Axial
      stiffness of constructs and bone surface strains were compared between EBMP and
      CC constructs. RESULTS: Stems were impacted without creating femoral fissures or
      fractures. Stem impaction distances were larger for EBMP stems than for CC stems.
      Mean axial stiffness of EBMP constructs was lower than mean axial stiffness of CC
      constructs. Subsidence did not differ between groups. Bone strains varied among
      strain gauge positions and were largest at the distal aspect of the stems. At a
      load of 1,600 N, bones strains were higher in CC constructs than in EBMP
      constructs for 2 of 4 medial strain gauges. CONCLUSIONS AND CLINICAL RELEVANCE:
      EBMP stems were successfully impacted and stable and led to a focal decrease in
      bone strain; this may represent an acceptable option for conventional or custom
      joint replacement.

PMID- 20807151
TI  - Effect of the reproductive state of female alpacas on embryonic mortality rate.
AB  - OBJECTIVE: To study the effect of the reproductive state of female alpacas (ie,
      maiden [never bred before], barren [bred but failed to conceive or maintain
      pregnancy in previous breeding season], or gave birth and currently lactating) on
      embryonic mortality rate. ANIMALS: 167 female alpacas (54 lactating, 44 barren,
      and 69 maiden) that ovulated following a single breeding. PROCEDURES: During the
      first 45 days following breeding, female alpacas underwent periodic transrectal
      ultrasonography to determine the presence or absence of an embryonic vesicle.
      Serum progesterone concentrations were determined during the same period.
      Embryonic survival rate was analyzed for each group of females (lactating,
      barren, and maiden). RESULTS: The presence of an embryonic vesicle or embryo was
      positively associated with high serum progesterone concentrations (>2 ng/mL). The
      embryonic mortality rate in barren females (21/44 [47.7%]) was significantly
      higher than in maiden (20/69 [29.0%]) and lactating (16/54 [29.6%]) females. In
      females that underwent embryonic loss (n=57), 3 patterns of events in terms of
      serum progesterone concentrations were identified: concomitant decrease of serum
      progesterone concentration and embryonic loss (24/57 [42.1%]), decrease in serum
      progesterone concentration before embryonic loss (12/57 [21.1%]), and persistent
      serum progesterone concentrations beyond embryonic loss (21/57 [36.8%]). Patterns
      of serum progesterone concentration and embryonic loss did not differ
      significantly among lactating, barren, and maiden female alpacas. CONCLUSIONS AND
      CLINICAL RELEVANCE: Embryonic loss in alpacas occurred without any discernible
      pattern in serum progesterone concentrations. Barren female alpacas had the
      highest embryonic mortality rate.

PMID- 20807152
TI  - Glomerular filtration rate in dogs as estimated via plasma clearance of inulin
      and iohexol and use of limited-sample methods.
AB  - OBJECTIVE: To compare plasma clearance of inulin and iohexol determined by use of
      9 plasma samples for evaluation of glomerular filtration rate in dogs and to
      evaluate limited-sample approaches for evaluation of plasma clearance of these
      markers. ANIMALS: 43 dogs of various breeds that weighed between 5.5 and 63 kg
      and that had various degrees of renal function. PROCEDURES: 9 plasma samples were
      obtained from each dog at 5 minutes to 6 hours after IV bolus injection of
      iohexol and inulin. Clearance was calculated by use of results for all 9 samples
      (ie, reference method). Results for 3 limited-sample strategies for determination
      of plasma clearance of iohexol and inulin were compared with results for the
      reference method. RESULTS: Mean clearance of inulin and iohexol for the reference
      method was 2.72 and 2.48 mL/min/kg, respectively. The mean difference between
      clearance of these 2 markers for the reference method was 0.24 mL/min/kg. In
      general, use of the limited-sample strategies yielded clearance values similar to
      those for the reference method. More accurate estimates of clearance were
      obtained for iohexol than for inulin by use of the limited-sample methods.
      CONCLUSIONS AND CLINICAL RELEVANCE: Use of iohexol and inulin yielded similar but
      not identical results for plasma clearance. Accuracy for limited-sample methods
      would be acceptable for many clinical and research situations.

PMID- 20807153
TI  - Supraventricular tachycardia in neonates: antiarrhythmic drug choice dilemma.
AB  - Supraventricular tachycardia (SVT), being atrioventricular reentry the underlying
      mechanism, is the most frequently tachyarrhythmia requiring a medical treatment
      in infants with no cardiac disease. The acute treatment of a single episode of
      SVT has generally an excellent prognosis. An antiarrhythmic prophylaxis of SVT
      recurrences is usually recommended during the first year of life. Although many
      efficient drugs are available for the SVT treatment, a careful risk-benefit
      analysis of each single case should suggest the correct drug choice.

PMID- 20807154
TI  - Screening of postpartum depression: comparison between mothers in the neonatal
      intensive care unit and in the neonatal section.

PMID- 20807155
TI  - Oxidative stress and antioxidant strategies in newborns.
AB  - Oxidative stress (OS) is defined as an unbalance between prooxidant and
      antioxidant factors that can lead to cellular and tissue damage.The newborn,
      especially if preterm, is highly prone to OS and to the toxic effect of free
      radicals (FR). At birth, the newborn is exposed to a relatively hyperoxic
      environment caused by an increased oxygen bioavailability with greatly enhanced
      generation of FR. Additional sources (inflammation, hypoxia, ischemia, glutamate,
      and free iron release) occur magnifying OS. In the preterm baby, the perinatal
      transition is accompanied by the immaturity of the antioxidant systems and the
      reduced ability to induce efficient homeostatic mechanisms designed to control
      overproduction of cell-damaging FR. Improved understanding of the
      pathophysiological mechanism involved in perinatal brain lesions helps to
      identify potential targets for neuroprotective interventions, and the knowledge
      of these mechanisms has enabled scientists to develop new therapeutic strategies
      that have confirmed their neuroprotective effects in animal studies. Considering
      the growing role of OS in preterm newborn morbidity in respect to the higher risk
      of FR damage in these babies, a strict control of oxygen administration, lutein,
      melatonin, and hypothermia show great promise as potential neuroprotectants. This
      review provides an overview of the pathogenesis of free radical-mediated diseases
      of the newborn and the antioxidant strategies for now tested to reduce the OS and
      its damaging effects.

PMID- 20807156
TI  - When anti-G and anti-C antibodies masquerade as anti-D antibody.
AB  - We describe a case of a pregnant woman with anti-C/anti-G antibodies masquerading
      as anti-D antibodies. Further, confirmation of anti-D antibody is recommended
      with adsorption-elution studies to confirm the true antibody status. This will
      avoid the consequence of withholding Rh immunoglobulin prophylaxis in cases when
      anti-D antibodies are not present.

PMID- 20807157
TI  - Transient tachypnea of the newborn: what is new?
AB  - An infant born by cesarean delivery is at risk of having excessive pulmonary
      fluid which makes predisposition to transient tachypnea of the newborn (TTN),
      because fetal thorax compression during labor leads to the loss of large volumes
      liquid from the lungs. At birth, the pulmonary epithelium switches from
      predominantly facilitated Cl- secretion to predominantly active Na+ reabsorption
      with the increase expression epithelial Na+ -channels (ENaC). Diminished activity
      or immaturity of this process may contribute to the development of TTN. Familial
      clustering of some TTN cases shows a genetic predisposition in the developing of
      this disorder. Antenatal glucocorticoids induce lung Na+ reabsorption by
      increasing the number and activity of channels even in hypoxia. Since a large
      release of fetal adrenaline occurs late in labor stimulating ENaC to start
      reabsorbing lung fluids, aerolized beta-agonists may be used in the treatment.
      Genetic predisposition for beta-adrenergic hyporesponsiveness may cause TTN in
      newborn period, and asthma/wheezing in older age groups. Although furosemide
      accelerates lung fluid resorption and cause pulmonary vasodilatation, oral or
      aerosolized furosemide cannot be recommended as treatment for TTN unless
      additional data become available.

PMID- 20807158
TI  - Cesarean or vaginal delivery for the breech fetus at the threshold of viability:
      results from a maternal-fetal medicine specialists survey.
AB  - OBJECTIVE: To determine how United States Maternal-Fetal medicine specialists
      recommend delivery of a breech fetus at the threshold of viability. METHODS: U.S.
      Society for Maternal-Fetal Medicine (SMFM) members were surveyed about;
      geographic location, practice type, whether they performed deliveries, definition
      of threshold for viability, recommendations for delivery of a breech fetus at the
      threshold of viability, and if the current medical-legal climate had any bearing
      on their decisions. Chi-Square and Fisher's Exact tests were used for analysis.
      RESULTS: 510 SMFM members responded to the questionnaire. The highest percentage
      of respondents stated '23 weeks' (31%) as the cutoff for viability, followed by
      '24 weeks' (21%) and '23 weeks or 500 g' (10%). Seventy percent recommended
      cesarean delivery for a breech fetus at the threshold of viability. The majority
      of respondents based their decision on 'published data' or 'expert opinion',
      however, 58.6% reported they felt current medical evidence was inadequate to
      support a recommendation. Fifty-three percent stated their recommendations are
      affected by medical-legal concerns. CONCLUSION: The majority of U.S. maternal
      fetal-medicine specialists who responded would recommend cesarean delivery for a
      breech fetus at the threshold of viability, despite the belief that there is
      inadequate evidence in the literature to support this recommendation.

PMID- 20807160
TI  - Congenital cytomegalovirus infection: treatment, sequelae and follow-up.
AB  - Cytomegalovirus (CMV) is the most common cause of congenital infection affecting
      about 1% of all the live births worldwide. Its prevalence in the developed world
      seems to be slightly lower, ranging between 0.6 and 0.7%. Symptoms can be
      detected at birth in 10-15% of the congenitally infected of which 50-90% will
      develop sequelae, the most frequent being sensorineural hearing loss (SNHL),
      visual defect, psychomotor impairment, mental retardation, cerebral palsy and
      seizures. Eighty-five to 90% of the infected newborns are asymptomatic but 10-15%
      of them are equally at risk for sensorineural sequelae, like 20-30% of all the
      infected children. Therefore it is important a time prolonged and closer follow
      up of infected children that we propose should be until 6 years of age. This
      should lead to an early intervention, better management and eventually even
      control the long-term sequelae. Infants born with symptomatic congenital
      infection have a worse prognosis than those with no evidence of clinical disease,
      and ganciclovir (GCV) intravenous 6 mg/kg every 12 h for 6 weeks is the most used
      therapy for symptomatic newborns. Valganciclovir (V-GCV) syrup is a pro-drug of
      GCV and presents high oral bioavailability. To date, it is possible to administer
      this drug at home, and the tolerability profile may allow for wider indications
      and longer treatments.

PMID- 20807159
TI  - Our clinical experience about prenatal diagnosis and neonatal outcomes of fetal
      central nervous system anomalies.
AB  - OBJECTIVE: To present a retrospective analysis of the prenatal diagnosis and the
      outcome of fetuses diagnosed with central nervous system (CNS) anomalies.
      MATERIALS AND METHODS: We reviewed the medical records and ultrasound data of 69
      cases diagnosed with CNS anomalies from 2007 to 2008. We described the prenatal
      diagnosis, associated findings, and outcome of these patients. RESULTS: Sixty
      nine patients were diagnosed with CNS anomalies. Of these, 31 had
      ventriculomegaly + hydrocephaly, 14 had spina bifida + meningomyelosel, 5 had
      choroid plexus cyst, 5 had Dandy Walker malformation, 3 had sacrocoxigeal
      teratoma, 2 had encephalosel, 1 had microcephaly, and 1 had Arnold Chiari
      malformation. Eight amniocentesis, three cord blood sampling, and two fetal
      reduction procedure were performed. Nine pregnancy termination and 36 delivery
      were performed. Neurosurgical correction was performed for neonates with spina
      bifida, hydrocephaly and sacrocoxigeal teratoma. Twenty-one neonates were
      discharged with cure, 4 neonates with follow-up, 7 neonates with paraplegia, and
      13 neonates died. CONCLUSION: The outcome of fetuses with CNS anomalies was shown
      to depend mainly on the degree of neural tube defect and the associated anomalies
      were the most important factors in surviving.

PMID- 20807161
TI  - Morbidity rates in late preterms born to HIV-mothers.
AB  - The rate of late preterm delivery has increased in the general population, and
      the late preterm infants have a higher incidence of morbidity compared to term
      newborns. Late preterm data are lacking in born to HIV-infected mother. We showed
      that, among 202 live births, late preterm delivery was higher in born to HIV
      infected mothers than in the general population while their morbidity was lower.

PMID- 20807162
TI  - The world of twins: an update.
AB  - In last years, owing to the widespread availability of assisted-reproduction
      technology, multiple pregnancy rates in Western countries have increased. In twin
      pregnancies, an increased rate of gestational complications, intrauterine growth
      restriction (IUGR), preterm birth and severe perinatal conditions is present.
      These complications are more frequent in monozygotic twins compared to dizygotic
      twins as well as an increased relative risk of chromosomal abnormalities and
      congenital malformation. Monochorionic twins are at higher risk for
      complications, since they share a common placenta where an imbalance in
      unidirectional arteriovenous anastomoses can lead to twin&#x2013;twin transfusion
      syndrome. This extremely dangerous condition, if not early identified, can
      determine severe fetal complications with mortality rates that, in case of no
      treatment, reaches 90%. Laser photocoagulation is the treatment of choice in
      severe twin-to-twin transfusion syndrome with high survival rate. IUGR occurs
      more frequently in MC twins and along with prematurity and perinatal pathology is
      considered an important determinant of developmental delay.

PMID- 20807163
TI  - Acute kidney injury in critically ill infants: the role of urine Neutrophil
      Gelatinase-Associated Lipocalin (NGAL).
AB  - Acute kidney injury (AKI) has emerged as an important health problem in the
      intensive care units, especially among infants delivered prematurely. Recent
      efforts to define and characterize AKI have led to studies of early AKI detection
      and will ultimately contribute to improvements in AKI outcomes. The discovery of
      biomarkers for AKI that might enable early recognition and clinical intervention
      to limit renal injury is therefore of intense contemporary interest. Neutrophil
      gelatinase-associated lipocalin (NGAL) is the most promising among all emerging
      markers for AKI; specifically, urine NGAL (uNGAL) predicts renal failure much
      earlier than serum creatinine. The recent availability of an automated
      immunoassay for measuring uNGAL in the clinical practice permits to introduce the
      test in emergency, having a turn around time (TAT) closely comparable with that
      of serum creatinine. On the basis of data reported in the literature, it is
      reasonable to forecast an increasing clinical use of uNGAL capable to change our
      approach to the diagnosis and leading to better preventative and therapeutic
      interventions which will improve outcomes of critically ill infants with acute
      kidney disease.

PMID- 20807164
TI  - Increased leukocyte ABCA1 gene expression in post-menopausal women on hormone
      replacement therapy.
AB  - OBJECTIVE: The ATP binding cassette A1 (ABCA1) is a key participant in the
      reverse cholesterol process whereby mediates cholesterol efflux directly to HDL
      particles. The aim of this study was to investigate whether long-term treatment
      with conventional hormone replacement therapy (HRT) in post-menopausal women
      could affect their leukocytes ABCA1 expression. Changes in various serum lipids
      and lipoprotein fractions were also investigated. MATERIAL AND METHODS: A total
      of 60 non-obese normolipidaemic post-menopausal women treated with oral oestrogen
      together with progestin therapy for 3 months were selected. Leukocytes ABCA1 gene
      expression and serum lipid and lipoprotein concentrations were measured at the
      start and end of the HRT. RESULTS: HRT led to significant increases in HDL
      cholesterol (P = 0.001) and apoA-I (P = 0.046) and significant decrease in apoB
      (P = 0.049) and LDL cholesterol (P = 0.022) when compared with the baseline
      levels. Analysis of leukocytes ABCA1 mRNA showed a significant increase in ABCA1
      gene expression after HRT (P = 0.001). There was also a significant inverse
      association (r =  -0.28, P = 0.03) between ABCA1 gene expression and log TG/HDL
      cholesterol changes related to HRT. CONCLUSION: The beneficial cardiovascular
      effects of HRT could be explained, at least in part, by increasing the ABCA1 gene
      expression.

PMID- 20807165
TI  - Metabolic syndrome in adolescents with polycystic ovary syndrome.
AB  - The aim of the presented study is to evaluate metabolic features in adolescents
      with polycystic ovary syndrome (PCOS) in comparison with age- and BMI-matched
      subjects. Forty-three adolescents with PCOS according to ESHRE criteria were
      prospectively evaluated and compared with 48 control subjects. Blood sampling was
      done in the early follicular phase of menstrual cycle, between 1st and 5th day,
      for plasma glucose, total and high-density lipoprotein (HDL)-cholesterol,
      triglycerides, insulin and C peptide. The diagnosis of metabolic syndrome was
      done according to IDF adolescent criteria. Adolescents with PCOS have increased
      low-density lipoprotein (LDL)-cholesterol (p < 0.002), decreased HDL-cholesterol
      (p <0.0007) and increased C peptide levels (p < 0.02) in comparison with healthy
      adolescents. Total cholesterol, triglycerides, fasting blood glucose, fasting
      insulin, HOMA-IR, waist-to-hip ratio, systolic and diastolic blood pressure did
      not differ between the groups. There was no difference when we compared the
      prevalence of adolescents with at least one feature of metabolic syndrome between
      PCOS (17 from 43) and healthy controls (27 from 48). In conclusion, adolescents
      with PCOS have less favourable blood lipid profiles with higher LDL-cholesterol
      and lower levels of HDL-cholesterol and are more insulin resistant than their
      healthy counterparts having higher fasting C peptide levels.

PMID- 20807166
TI  - Dyslipidemia in women with polycystic ovary syndrome: incidence, pattern and
      predictors.
AB  - One hundred forty-two women with polycystic ovary syndrome (PCOS) with an average
      body mass index (BMI) of 29.1 kg/m(2) and average age of 25.12 years were
      studied. By BMI, 30.2% were normal, 38.0% were overweight and 31.6% were obese.
      Thirty-one eumenorrheic women matched for BMI and age, with no evidence of
      hyperandrogenism, were recruited as controls. The incidence of dyslipidemia in
      the PCOS group was twice that of the Control group (76.1% versus 32.25%). The
      most frequent abnormalities were low high-density lipoprotein cholesterol (HDL-C;
      57.6%) and high triglyceride (TG) (28.3%). HDL-C was significantly lower in all
      subgroups of women with PCOS when compared to the subgroups of normal women. No
      significant differences were seen in the total cholesterol (p = 0.307), low
      density lipoprotein cholesterol (LDL-C; p = 0.283) and TGs (p = 0.113) levels
      among the subgroups. An independent effect on HDL-C was detected for glucose (p =
      0.004) and fasting insulin (p = 0.01); on TG for age (p = 0.003) and homeostatic
      model assessment insulin resistance (p = 0.03) and on total cholesterol and LDL-C
      for age (p = 0.02 and p = 0.033, respectively). In conclusion, dyslipidemia is
      common in women with PCOS, mainly due to low HDL-C levels. BMI has a significant
      impact on this abnormality.

PMID- 20807167
TI  - Ovarian reserve in young women with low birth weight and normal puberty: a pilot
      case-control study.
AB  - AIM: Studies indicate that women born small for gestational age (SGA) have
      impaired ovarian function. The origin of this ovarian dysfunction is still
      debatable. The aim of this study was to compare ovarian ageing between girls born
      appropriate for gestational age (AGA) and SGA. Therefore, we measured Luteinizing
      hormone (LH), Follicle-stimulating hormone (FSH), E2, Anti-Mullerian hormone
      (AMH) levels and the pituitary response to endogenous Gonadotropin-releasing
      hormone (GnRH) in adolescent girls born SGA and AGA. METHODS: A case-controlled
      pilot study consisting of seven SGA women (birth weight < 10th percentile AGA)
      and 13 AGA women with regular menstrual cycles, age 19.9 +/- 0.42). Early
      follicular FSH, LH, Oestradiol (E2) and AMH levels were measured. After baseline
      samples, 100 MUg GnRH was administered intravenously and at 30, 60 and 90 min
      blood samples were taken to measure gonadotropin levels and to compute the
      response to endogenous GnRH. RESULTS: Mean follicular phase LH, FSH, E2 and AMH
      levels did not significantly differ between young women born SGA and AGA.
      Furthermore, the response to endogenous GnRH showed no significant differences
      either. CONCLUSIONS: We concluded against extension of this pilot study. Based on
      our observations it seems unlikely that limited ovarian reserve is a predominated
      problem in adolescent SGA.

PMID- 20807168
TI  - Is pronuclear scoring a really good predictor for ICSI cycles?
AB  - BACKGROUND/AIMS: Since the assessments of the morphology of oocytes, zygotes
      and/or embryos are of crucial importance to select the best candidate for
      pregnancy, many morphological evaluation tools have been proposed. Although
      embryo scoring, particularly cleavage and blastocyst stages, is more convincing
      due to successful results, zygote scoring still have a bias as different
      outcomes. In the current study, we designed a prospective study to test the
      reliability of zygote scoring by focusing on zygote evaluation techniques and its
      relation with embryo development and embryo selection for transfer. METHODS: A
      total of 1215 mature oocytes from 139 couples were evaluated for the study.
      RESULTS: There is no correlation between published zygote scoring technique and
      embryo development. CONCLUSIONS: We conclude that the inconsistency of data
      obtained from zygote scoring might be caused by the static nature of pronuclear
      stage embryos and thus pronuclear scoring seems to be unreliable evaluation
      technique for embryo selection.

PMID- 20807169
TI  - Robotic assisted microsurgery in hypothenar hammer syndrome: a case report.
AB  - We report the case of a patient with bilateral hypothenar hammer syndrome. The
      therapeutic decision was to resect a thrombosed segment of the distal ulnar
      artery then reconstruct it using a forearm venous graft. The original aspect of
      this case concerns the microsurgical technique employed: All vascular sutures
      were made by separate nylon 10/0 stitches using a da Vinci S surgical robot. No
      particular problems were observed postoperatively and, except for some cold
      related pain, the patient no longer experienced any symptoms at 6 months post
      surgery. This clinical case shows that robots may be employed for some specific
      tele-microsurgical procedures.

PMID- 20807170
TI  - Imageless navigation assisted total knee arthroplasty with comprehensive gap
      balancing in medial osteoarthritic varus knees with anatomic variations.
AB  - This study retrospectively compares the postoperative alignment of imageless
      navigation assisted (INA) total knee arthroplasties (TKAs) using comprehensive
      gap balancing with that of conventional TKAs in 72 medial osteoarthritic varus
      knees with coronal plane anatomic variations of the distal femur and proximal
      tibia. The navigation group showed significantly lower postoperative differences
      in the mechanical axis (MA) of the lower limb (p = 0.003), with fewer outliers (p
      = 0.03), better femoral component positioning relative to the MA (p = 0.02), and
      less difference between the weight-bearing MA of the lower limb and the MA of the
      femur (p = 0.003) and tibia (p = 0.005). INA comprehensive gap balancing TKA
      provides a better correction of leg alignment and better orientation of
      components with respect to the MA in medial osteoarthritic varus knees with
      lateral bowing of the femoral shaft and external rotation of the femur and/or
      proximal tibia vara, thus indicating the superiority of this approach over the
      conventional technique in such situations.

PMID- 20807171
TI  - Individual variability of response and non-response to acetyl salicylic acid
      after cardiac surgery.
AB  - Insufficient inhibition of platelet function by acetyl salicylic acid (ASA) or
      other platelet inhibitors is a risk factor for arterial thrombosis in
      cardiovascular patients. We wanted to collect and analyse information on the
      frequency and probable causes of non-response to ASA in patients prior to and
      after cardiac surgery. One hundred and one patients (mean age 68 +/- 9 years)
      undergoing cardiac surgery (98 patients with coronary bypass grafting, 18 cases
      had combined valve replacement, and three patients with only valve replacement)
      were enrolled. Post-operatively all patients received metamizole for analgesia.
      Platelet aggregation in platelet-rich plasma was induced by arachidonic acid (AA;
      1.6 mM) or ADP (3 mM) in the absence and presence of exogenous ASA (100 uM). ASA
      non-response was defined as a maximum AA-induced aggregation of >30%. Eighty
      eight patients had pre-operative medication with ASA (100 mg/d), and ASA non
      response was found in 24%. Irrespective of whether or not ASA medication was
      continued immediately after surgery, incidence of non-response increased to 55%
      at the first post-operative day. During continuous post-operative ASA medication
      (100 mg/d), 65% of patients were non-responder at fifth-7th post-operative day.
      When estimated on the basis of exogenously added ASA, non-response was observed
      pre-operative in 10%, at first post-operative day in 53% and at fifth-7th post
      operative day in 39% of the patients. Twenty six of the 52 patients who did not
      adequately respond to exogenous ASA at the first post-operative day became
      responders when tested at the fifth-7th post-operative day, and 13 of the 46
      responders became non-responders. The conversions were not due to small changes
      around the threshold of 30% aggregation but due to a highly significant decrease
      or increase in the extend of aggregation. Neither extracorporal circulation nor
      co-medication with clopidogrel had any significant influence on the platelet
      response to ASA medication or exogenously added ASA. Some non-steroidal
      analgesics, including metamizole, have been suggested to prevent inhibition of
      platelet cylcooxygenase by ASA. However, in 10 healthy volunteers we did not
      observe any interference of metamizole with the response to ASA. In conclusion,
      platelet response to ASA is markedly decreased after cardiac surgery. The
      underlying mechanisms and the clinical consequences of the post-operative
      instability of non-response to ASA need further evaluation.

PMID- 20807172
TI  - Coagulation status in coronary artery disease patients with type II diabetes
      mellitus compared with non-diabetic coronary artery disease patients using the
      PFA-100(r) and ROTEM(r).
AB  - Previous investigations in patients with coronary artery disease (CAD) revealed
      differences in thromboelastographic parameters indicating different states of
      coagulability. The aim of the present study was to investigate the coagulation
      status of patients with documented CAD and type II diabetes mellitus (DM) and non
      diabetic patients with coronary artery disease with the PFA-100(r) and the
      ROTEM(r). No differences were found in platelet function as measured with
      collagen/epinephrine (263.6 +/- 70.6 s vs. 254.6 +/- 65.3 s) and collagen/ADP
      cartridges (105.3 +/- 63.2 s vs. 90.6 +/- 47.3 s) in CAD patients with DM and CAD
      patients without DM. Measured with the EXTEM reagent of the ROTEM(r), mean
      maximum clot elasticity (MCE) in patients with CAD and DM (233.6 +/- 86.9) was
      significantly longer than in CAD patients without DM (186.7 +/- 54.5), (p =
      0.03). A similar result was seen using the INTEM reagent; patients with CAD and
      DM (234.4 +/- 83.9) showed a higher value for MCE than CAD patients without DM
      (190.8 +/- 57.8) which was of borderline significance (p = 0.053). Moreover, a
      weak trend for higher maximum clot firmness (MCF) was seen in CAD patients with
      DM compared with CAD patients without DM with the EXTEM reagent (68.1 +/- 7.5 vs.
      63.6 +/- 8.6, p = 0.08) and the INTEM reagent (68.4 +/- 7.2 vs. 64.1 +/- 8.2, p =
      0.09). The ROTEM(r) analysis indicates increased coagulability in patients with
      coronary artery disease and diabetes mellitus compared to non-diabetic CAD
      patients. Moreover, the ROTEM(r) device seems to be an appropriate and easy-to
      use tool to describe the coagulation status in these patients groups.

PMID- 20807173
TI  - Newborn platelets: lower levels of protease-activated receptors cause
      hypoaggregability to thrombin.
AB  - Newborn platelets show in vitro hypoaggregability to thrombin. Sensitivity of
      platelets to such a potent agonist is crucial for a functional clot formation.
      Nevertheless, newborns have an excellent hemostasis. We wanted to investigate the
      reason for this impairment by comparatively analysing levels of receptors known
      to be involved in thrombin signaling in newborn and adult platelets. Platelets of
      adult and cord blood were isolated, washed, and lysed. Resulting protein samples
      were separated by SDS-PAGE and blotted on nitrocellulose membranes. Receptors
      were visualized using immunodetection and evaluated densitometrically. Thrombin
      receptor activating peptide induced platelet aggregation was measured in citrated
      whole blood on a Multiplate analyzer. Statistical analysis was performed using
      SPSS 16.0. Significantly lower levels of protease-activated receptors (PAR1,
      PAR4) and higher levels of glycoprotein Ibalpha (GPIbalpha) were found in newborn
      platelets as compared to adult platelets. Platelet aggregation was lower in
      newborn samples than in adult controls and values correlated with the
      corresponding PAR levels. Our results suggest that lower levels of protease
      activated receptors contribute to the poor thrombin induced aggregation observed
      with newborn platelets, which can not be compensated by higher levels of
      GPIbalpha.

PMID- 20807174
TI  - A novel coaxial tube catheter for central nervous system infusions: performance
      characteristics in brain phantom gel.
AB  - We tested a novel neurocatheter in a brain-tissue gel model of drug infusion via
      convection-enhanced delivery (CED) for the treatment of a variety of neurological
      diseases. CED is an alternative to systemic administration of agents by
      intravenous or oral routes, which are often less effective or carry risk of
      systemic side effects. We investigated two co-axial tube devices, with outer
      diameters of 1.6 mm and 2.0 mm. Bromophenol blue dye was infused into 400 ml of
      0.6% agarose gel at 1 MUl/min for 1 h, with/without the inner and outer tubes
      Luer-locked at the proximal end, with/without the inner tube primed, and
      with/without the inner tube preloaded into the outer tube upon insertion into the
      gel. The unlocked, primed, and unloaded configuration produced infusions that
      resulted in significantly less (p < 0.05) entrapped air escaping into the gel and
      resulted in no reflux of infusate.

PMID- 20807175
TI  - Irradiation of rainbow trout at early life stages results in legacy effects in
      adults.
AB  - PURPOSE: Communication of signals from irradiated to non-irradiated fish has been
      demonstrated by our group for adults. Major questions are however, whether the
      effects persist for significant lengths of time (meaning there are memories or
      legacies of the exposure) and whether they are induced in young animals or very
      early stages in the life cycle. METHODS: To address these questions we used a
      reporter cell clonogenic bioassay to detect the effects of radiation exposure and
      of 'bystander' signals, emitted from irradiated fish, on non-irradiated fish. The
      legacy of radiation exposure or receipt of bystander signals was investigated in
      rainbow trout irradiated as eggs at 48 h, eyed eggs at one month, yolk sac larvae
      (YSL) at two months and juveniles at three months after fertilisation. The
      irradiated and bystander fish together with shams and unhandled husbandry
      controls were grown on in a hatchery and examined as they reached each of the
      remaining life stages. They were also re-examined as one-year-olds with and
      without further irradiation and finally examined as sexually mature two-year
      olds. RESULTS: The data indicate a clear legacy effect of irradiation at any
      early life stage in the adult fish. CONCLUSION: The data suggest that bystander
      signals can be transmitted in vivo and once induced are persistent during the
      animals' lifespan.

PMID- 20807176
TI  - Mobile phone radiation-induced free radical damage in the liver is inhibited by
      the antioxidants N-acetyl cysteine and epigallocatechin-gallate.
AB  - PURPOSE: To investigate oxidative damage and antioxidant enzyme status in the
      liver of guinea pigs exposed to mobile phone-like radiofrequency radiation (RFR)
      and the potential protective effects of N-acetyl cysteine (NAC) and
      epigallocatechin-gallate (EGCG) on the oxidative damage. MATERIALS AND METHODS:
      Nine groups of guinea pigs were used to study the effects of exposure to an 1800
      MHz Global System for Mobile Communications (GSM)-modulated signal (average whole
      body Specific Absorption Rate (SAR) of 0.38 W/kg, 10 or 20 min per day for seven
      days) and treatment with antioxidants. RESULTS: Significant increases in
      malondialdehyde (MDA) and total nitric oxide (NO(x)) levels and decreases in
      activities of superoxide dismutase (SOD), myeloperoxidase (MPO) and glutathione
      peroxidase (GSH-Px) were observed in the liver of guinea pigs after RFR exposure.
      Only NAC treatment induces increase in hepatic GSH-Px activities, whereas EGCG
      treatment alone attenuated MDA level. Extent of oxidative damage was found to be
      proportional to the duration of exposure (P < 0.05). CONCLUSION: Mobile phone
      like radiation induces oxidative damage and changes the activities of antioxidant
      enzymes in the liver. The adverse effect of RFR may be related to the duration of
      mobile phone use. NAC and EGCG protect the liver tissue against the RFR-induced
      oxidative damage and enhance antioxidant enzyme activities.

PMID- 20807178
TI  - Luminescence characteristics for identifying irradiated black soybeans.
AB  - PURPOSE: Considering the commercial use of food irradiation and the prevalence of
      international trade of irradiated food and agricultural commodities, black
      soybeans originating from China or Korea were irradiated at 0-5 kGy.
      Photostimulated luminescence (PSL) and thermoluminescence (TL) were investigated
      for their ability to identify characteristics that would distinguish irradiated
      from non-irradiated samples. MATERIALS AND METHODS: Dried black soybeans [Glycine
      max (L.) Merr.] were irradiated using a Co-60 gamma irradiator or an electron
      beam accelerator and then analysed by PSL and TL. RESULTS: PSL photon counts were
      higher in irradiated samples than in non-irradiated ones and increased with
      applied doses, making it possible to distinguish irradiated from non-irradiated
      samples. The TL analysis revealed glow curves (TL1) with low intensity for non
      irradiated samples but a higher intensity (approximately 200 degrees C) for
      irradiated samples, showing increased intensities with radiation dose. The
      minerals were re-irradiated at 1 kGy and the second TL glow curve (TL2) was
      measured. Based on the calculated TL ratios (TL1/TL2) and the shape of TL1 glow
      curves, the irradiated samples could be distinguished from non-irradiated ones.
      CONCLUSIONS: PSL and TL are effective screening and reference methods for
      distinguishing gamma ray or electron beam irradiated black soybeans from non
      irradiated black soybeans.

PMID- 20807177
TI  - The heritability of G2 chromosomal radiosensitivity and its association with
      cancer in Danish cancer survivors and their offspring.
AB  - PURPOSE: To investigate the relationship between chromosomal radiosensitivity and
      early-onset cancer under the age of 35 years and to examine the heritability of
      chromosomal radiosensitivity. MATERIALS AND METHODS: Peripheral blood lymphocytes
      were cultured for 72 hours prior to being irradiated with 0.5 Gy, 300 kV X-rays.
      Colcemid was added to cultures 30 min post-irradiation. Cultures were harvested
      90 min post-irradiation and analysed for chromatid gaps and breaks. Heritability
      was estimated using Sequential Oligogenic Linkage Analysis Routines (SOLAR)
      software and by segregation analysis. RESULTS: Elevated radiosensitivity was seen
      for seven out of 29 (24.1%) cancer survivors, three out of 29 (10.3%) partners
      and 10 out of 53 (20.8%) offspring. Although the proportion of individuals
      displaying enhanced radiosensitivity was twice as high in both the cancer
      survivor and offspring groups than the partner controls, neither reached
      statistical significance. Heritability analysis of the radiosensitive phenotype
      suggested 57.9-78.0% of the variance could be attributed to genetic factors.
      CONCLUSION: An association between G(2) chromosomal radiosensitivity and
      childhood and young adult cancer is suggested but was not statistically
      significant. In contrast, there is strong evidence for heritability of the
      radiosensitive phenotype. The cancer survivors included a broad range of
      malignancies and future studies should focus on specific cancers with known or
      likely faults in deoxyribonucleic acid (DNA) damage recognition and repair
      mechanisms.

PMID- 20807179
TI  - Pulse modulated 900 MHz radiation induces hypothyroidism and apoptosis in thyroid
      cells: a light, electron microscopy and immunohistochemical study.
AB  - PURPOSE: In the present study we investigated the possible histopathological
      effects of pulse modulated Radiofrequency (RF) fields on the thyroid gland using
      light microscopy, electron microscopy and immunohistochemical methods. MATERIALS
      AND METHODS: Two months old male Wistar rats were exposed to a 900 MHz pulse
      modulated RF radiation at a specific absorption rate (SAR) of 1.35 Watt/kg for 20
      min/day for three weeks. The RF signals were pulse modulated by rectangular
      pulses with a repetition frequency of 217 Hz and a duty cycle of 1:8 (pulse width
      0.576 ms). To assess thyroid endocrine disruption and estimate the degree of the
      pathology of the gland, we analysed structural alterations in follicular and
      colloidal diameters and areas, colloid content of the follicles, and height of
      the follicular epithelium. Apoptosis was confirmed by Transmission Electron
      Microscopy and assessing the activites of an initiator (caspase-9) and an
      effector (caspase-3) caspases that are important markers of cells undergoing
      apoptosis. RESULTS: Morphological analyses revealed hypothyrophy of the gland in
      the 900 MHz RF exposure group. The results indicated that thyroid hormone
      secretion was inhibited by the RF radiation. In addition, we also observed
      formation of apoptotic bodies and increased caspase-3 and caspase-9 activities in
      thyroid cells of the rats that were exposed to modulated RF fields. CONCLUSION:
      The overall findings indicated that whole body exposure to pulse-modulated RF
      radiation that is similar to that emitted by global system for mobile
      communications (GSM) mobile phones can cause pathological changes in the thyroid
      gland by altering the gland structure and enhancing caspase-dependent pathways of
      apoptosis.

PMID- 20807180
TI  - Solar radiation induced skin damage: review of protective and preventive options.
AB  - PURPOSE: Solar energy has a number of short- and long-term detrimental effects on
      skin that can result in several skin disorders. The aim of this review is to
      summarise current knowledge on endogenous systems within the skin for protection
      from solar radiation and present research findings to date, on the exogenous
      options for such skin photoprotection. RESULTS: Endogenous systems for protection
      from solar radiation include melanin synthesis, epidermal thickening and an
      antioxidant network. Existing lesions are eliminated via repair mechanisms. Cells
      with irreparable damage undergo apoptosis. Excessive and chronic sun exposure
      however can overwhelm these mechanisms leading to photoaging and the development
      of cutaneous malignancies. Therefore exogenous means are a necessity. Exogenous
      protection includes sun avoidance, use of photoprotective clothing and sufficient
      application of broad-spectrum sunscreens as presently the best way to protect the
      skin. However other strategies that may enhance currently used means of
      protection are being investigated. These are often based on the endogenous
      protective response to solar light such as compounds that stimulate pigmentation,
      antioxidant enzymes, DNA repair enzymes, non-enzymatic antioxidants. CONCLUSION:
      More research is needed to confirm the effectiveness of new alternatives to
      photoprotection such as use of DNA repair and antioxidant enzymes and plant
      polyphenols and to find an efficient way for their delivery to the skin. New
      approaches to the prevention of skin damage are important especially for specific
      groups of people such as (young) children, photosensitive people and patients on
      immunosuppressive therapy. Changes in public awareness on the subject too must be
      made.

PMID- 20807181
TI  - The role of nucleophosmin/B23 in radiation-induced chromosomal instability in
      human lymphoblastoid cells of different p53 genotypes.
AB  - PURPOSE: To investigate the role of nucleophosmin (NPM/B23) in radiation-induced
      chromosomal instability and apoptosis in human lymphoblastoid cells with
      different protein 53 (p53) status. MATERIALS AND METHODS: Wild type (wt) p53 TK6
      and mutant type (mt) p53 WTK1 with or without short hairpin RNA (shRNA)-mediated
      silencing of NPM, TK6 with or without short interfering RNA (siRNA)-mediated
      silencing of p53 (p53i and NEGi) were irradiated with 4 Gy gamma-rays. Six to 48
      h after irradiation, the index of apoptosis, chromosome aberration, cell cycle
      distribution and the levels of total NPM and phosphorylated-threonine 199
      (pThr199) NPM proteins were measured. Cells in some dishes were treated with 10
      MUM Olomoucine (OLO) for 3 h before irradiation and remained in the medium after
      irradiation. RESULTS: The rates of radiation-induced apoptosis in TK6 and
      TK6/NEGi were about 2-fold of those in WTK1 and TK6/p53i, while the frequencies
      of polyploidy in TK6 and TK6/NEGi were obviously lower than those in WTK1 and
      TK6/p53i. Moreover, after irradiation, pThr199 NPM levels increased significantly
      in WTK1 and TK6/p53i, and slightly increased in TK6 and TK6/NEGi, indicating that
      the increased level of pThr199 NPM was related to p53 status. When Thr199
      hyperphosphorylation of NPM was inhibited by OLO or when NPM was knocked down, we
      found that radiation-induced apoptosis was more pronounced and polyploidy
      formation was reduced as compared with negative control while the magnitude of
      these changes in TK6 was obviously higher than that in WTK1, indicating that NPM
      has an antagonistic interaction with wt p53. CONCLUSIONS: NPM/B23 plays an
      important role in protecting cells from radiation-induced apoptosis and
      increasing polyploidy formation via either a p53 or non-p53 pathway.

PMID- 20807183
TI  - The use of pressure mapping for seating posture characterisation in  children
      with cerebral palsy.
AB  - PURPOSE: To investigate the feasibility of using pressure mapping for the
      characterisation of the seated posture of children with cerebral palsy (CP).
      METHOD: Analysis of pressure mapping readings and video of children seated in a
      seating system during two assessments: The first assessment involved the pressure
      mapping of non-disabled children during a standardised protocol, and the second
      one involved the pressure mapping of children with CP performing daily life
      activities. RESULTS: It was possible to detect periods of activity of the
      children from pressure readings using the mean variation of pressure.
      Additionally, several parameters stemming from pressure readings were shown to be
      successful in assessing the posture of the children. The centre of pressure when
      positioned relative to the ischial tuberosities, allowed for recognition of
      'adverse postures' involving pelvic obliquity/medio-lateral trunk flexion or
      antero-posterior pelvic tilt/ trunk flexion-extension, as deviations from the
      centre point. The angle between the principal axis of the sensors' pressure and
      the medio-lateral axis of the seat was also proposed to characterise pelvic
      transverse rotation but could not be tested with the actual protocol.
      CONCLUSIONS: Pressure monitoring can be used to assess qualitatively and
      quantitatively sitting posture of children with CP.

PMID- 20807184
TI  - Tonapofylline: a selective adenosine-1 receptor antagonist for the treatment of
      heart failure.
AB  - IMPORTANCE OF THE FIELD: The heart failure and cardiorenal syndromes are major
      public health hazards, affecting one in five persons during their lifetime.
      Alternatives to traditional loop-diuretics, including vasopressin and adenosine
      A(1) receptor antagonists are now in development. AREAS COVERED IN THIS REVIEW:
      The pathophysiologic rationale for the use of tonapofylline, an intravenous and
      oral adenosine A(1) receptor antagonist, in patients with heart failure and/or
      the cardiorenal syndrome are reviewed. A comprehensive review of published
      literature describing its medicinal chemistry, pharmacokinetics, efficacy, safety
      and tolerability are provided. We searched the Medline/PubMed and Embase
      databases for the terms 'BG9928', 'tonapofylline', 'Adentri', 'adenosine', 'heart
      failure', 'renal failure' and 'cardiorenal syndrome' from 1 January 1992 to the
      present. References from pertinent manuscripts were also reviewed for additional
      relevant content. WHAT THE READER WILL GAIN: The reader will better appreciate
      the potential role of tonapofylline in patients with heart failure and/or the
      cardiorenal syndrome. Additionally, the reader will gain an understanding of the
      current state of drug development and the rationale for the need for continued
      research. TAKE HOME MESSAGE: Tonapofylline promotes natriuresis and diuresis, and
      may preserve glomerular filtration rate in patients with heart failure.
      Additionally, pilot data indicate that tonapofylline may be renoprotective in the
      setting of concomitant treatment with a loop-diuretic. Adverse effects were
      generally mild.

PMID- 20807185
TI  - Who is a True Chronobiologist?

PMID- 20807186
TI  - Conformational diseases: structural studies of aggregation of polyglutamine
      proteins.
AB  - Protein misfolding and aggregation into insoluble amyloid deposits are often
      associated with neurodegenerative disorders. In particular, the polyglutamine
      (polyQ) diseases are inherited disorders triggered by the expansion of the polyQ
      tract over its physiological length in the involved protein. The molecular
      mechanism of aggregation from the native protein into amyloids involves several
      steps including protein misfolding, aggregation into oligomers, which seems to be
      the most toxic species, and, finally rearrangements into mature fibrils. In the
      present contribution, we review studies, integrating computational and
      experimental approaches, of polyQ proteins, as well as of the details of the
      complicate aggregation mechanisms in which aberrant form of polyQ proteins are
      involved. These aspects are of crucial relevance for a complete understanding of
      the onset of polyQ conformational diseases and can also shed light on putative
      therapeutic targets and future development of aggregation inhibitors.

PMID- 20807187
TI  - Recent advances in ligand-based drug design: relevance and utility of the
      conformationally sampled pharmacophore approach.
AB  - In the absence of three-dimensional (3D) structures of potential drug targets,
      ligand-based drug design is one of the popular approaches for drug discovery and
      lead optimization. 3D structure-activity relationships (3D QSAR) and
      pharmacophore modeling are the most important and widely used tools in ligand
      based drug design that can provide crucial insights into the nature of the
      interactions between drug target and ligand molecule and provide predictive
      models suitable for lead compound optimization. This review article will briefly
      discuss the features and potential application of recent advances in ligand-based
      drug design, with emphasis on a detailed description of a novel 3D QSAR method
      based on the conformationally sample pharmacophore (CSP) approach (denoted CSP
      SAR). In addition, data from a published study are used to compare the CSP-SAR
      approach to the Catalyst method, emphasizing the utility of the CSP approach for
      ligand-based model development.

PMID- 20807188
TI  - Hypoxia-inducible factor-1 in arterial disease: a putative therapeutic target.
AB  - Hypoxia-inducible factor-1 (HIF-1) is a nuclear transcription factor that is
      upregulated in hypoxia and co-ordinates the adaptive response to hypoxia by
      driving the expression of over 100 genes. In facilitating tissues to adapt to
      hypoxia, HIF-1 may have a role in reducing the cellular damage induced by
      ischaemia, such as that seen in peripheral arterial disease (PAD), or following
      acute ischaemic insults such as stroke and myocardial infarction. This therefore
      raises the possibility of HIF-1 modulation in such contexts to reduce the
      consequences of ischaemic injury. HIF1 has further been implicated in the
      pathogenesis of atherosclerosis, abdominal aortic aneurysm (AAA) formation,
      pulmonary hypertension and systemic hypertension associated with obstructive
      sleep apnoea. Through a better understanding of the role of HIF-1 in these
      disease processes, novel treatments which target HIF-1 pathway may be considered.
      This review summarises the role of HIF-1 in arterial disease, specifically its
      role in atherosclerosis, ischaemic heart disease, in-stent restenosis following
      coronary revascularisation, stroke, PAD, AAA formation, pulmonary artery
      hypertension and systemic hypertension. The potential for exploiting the HIF-1
      signalling pathway in developing therapeutics for these conditions is discussed,
      including progress made so far, with attention given to studies looking into the
      use of prolyl-hydroxylase inhibitors.

PMID- 20807189
TI  - The emerging role of vascular endothelial growth factor (VEGF) in vascular
      homeostasis: lessons from recent trials with anti-VEGF drugs.
AB  - Vascular endothelial growth factor (VEGF) is an endogenous polypeptide that
      modulates angiogenesis in normal physiological conditions as well as in cancer.
      During angiogenesis, VEGF interacts with several other angiogenic factors,
      playing an important role in cell proliferation, differentiation, migration, cell
      survival, nitric oxide (NO) production, release of other growth factors and
      sympathetic innervation. Based on these mechanisms of action, several anti-VEGF
      drugs have been developed for cancer treatment. This review discusses the
      physiology and interactions of VEGF, its mechanisms of action and role in
      modulating vascular homeostasis. It also discusses the adverse cardiovascular
      effects of recently developed anti-VEGF drugs for the treatment of various types
      of cancer. A critical appraisal of the human studies on these drugs is provided.
      Furthermore, putative mechanisms for the onset of hypertension, the most common
      adverse cardiovascular effect, are discussed.

PMID- 20807190
TI  - Effects of insulin on the vasculature.
AB  - Revascularization procedures used for the treatment of cardiovascular disease can
      be associated with restenosis, although drug-coated stents have greatly reduced
      this complication. Both type 2 diabetes (T2DM) and metabolic syndrome (MetS) are
      associated with a high risk for atherosclerosis and restenosis. Insulin
      resistance, defined as the inability of insulin to exert its metabolic actions,
      characterizes both T2DM and MetS. Recent data suggest that insulin resistance is
      directly implicated in atherosclerosis/restenosis, because of the
      unresponsiveness to the vasculoprotective action of insulin, including its
      phosphoinositide 3-kinase (PI3K)-Akt-endothelial nitric oxide synthase mediated
      enhancement of endothelial function. However, insulin also has 'atherogenic'
      actions, including enhancement of vascular smooth muscle cell (VSMC)
      proliferation, which are mitogen-activated protein kinase-mediated. These
      'atherogenic' actions are less affected by insulin resistance, which mainly
      involves the PI3K pathway. The role of insulin in the atherosclerotic disease
      process is still highly controversial, where some investigators view insulin as a
      growth factor with pro-atherogenic effects while some others believe insulin
      resistance to be pro-atherogenic rather than insulin itself. We attempt to
      produce a balanced review with a focus on the effect of insulin in vivo, in
      animal models of atherosclerosis and restenosis.

PMID- 20807191
TI  - Current prospective of anti-IL-4, -IL-9, and -IL-13 therapies in allergic
      disease.
AB  - While the incidence of allergy and allergic diseases continues to increase, new
      drugs to treat these disorders have not been forthcoming. The mainstay of therapy
      continues to be inhaled steroids, leukotriene receptor antagonists,
      antihistamines and immunotherapy. Even though these drugs work for many patients
      there remains a group of individuals who fail to improve with these treatments.
      With the exception of immunotherapy, these drugs improve symptoms, but do not do
      anything to alter the course of disease. This review will cover recent patents
      and new drugs that target IL-4, IL-13 and IL-9, molecules involved not only in
      inflammation associated with disease, but also with the development of the immune
      repertoire necessary for the perpetuation of disease. Inhibition of these
      cytokines may lead to true immunomodulation of disease and finally give us drugs
      that cure the disease rather than just treat symptoms.

PMID- 20807192
TI  - Targeting interleukin (IL) 5 for asthma and hypereosinophilic diseases.
AB  - Although glucocorticosteroids are still the first line of treatment for chronic
      asthma, over the last two decades great advances have been made in understanding
      the pathogenesis of asthma that enabled the identification of new therapeutic
      targets for asthma treatment. The interleukin (IL) 5: eosinophil axis is a
      hallmark pathway of allergic inflammation that has received much attention.
      Indeed, IL-5 is known to regulate eosinophil differentiation, proliferation,
      priming and activation. Therefore, therapeutic agents targeting IL-5 have been
      generated. In this review we will discuss the effects of IL-5 on eosinophils and
      outline the signaling mechanism involved in IL-5-mediated effects. Furthermore,
      recent results from clinical trials targeting IL-5 in asthma and
      hypereosinophilic syndrome will be discussed and an overview of newly developed
      patents aimed to target IL-5 will be reviewed.

PMID- 20807193
TI  - TNF-alpha antagonism in severe asthma?
AB  - A small minority of patients with asthma have severe disease that is refractory
      or poorly responsive and remain persistently symptomatic despite maximal inhaled
      therapy. These patients represent an important unmet clinical need as they suffer
      considerable morbidity and mortality and consume a disproportionately large
      amount of health care resource. Tumour necrosis factor- alpha (TNF-alpha) is a
      pro-inflammatory cytokine that has been implicated in many aspects of the airway
      pathology in asthma. Evidence is emerging to suggest that it may play an
      important role in severe, refractory disease. The development of novel TNF-alpha
      antagonist has allowed us to test the role of this cytokine in vivo. Early
      studies demonstrated an improvement in asthma quality-of-life, lung function,
      airway hyperresponsiveness (AHR) and a reduction in exacerbation frequency, in
      patients treated with anti-TNF-alpha therapy. However, there is marked
      heterogeneity in response suggesting that benefit is likely to be reserved to a
      small sub-group. This view is supported by the lack of efficacy in later large
      clinical trials, although subgroups of responders were identified. Importantly,
      concerns have been raised about the safety of anti-TNF-alpha therapies in severe
      asthma. Therefore, current evidence suggests that the risk of anti- TNF-alpha
      therapies outweighs benefit in severe asthma. In this review, we will discuss the
      role of TNF-alpha biology and its role in severe asthma, the clinical trials
      conducted so far and summarize the patents related to TNF-alpha and the
      antagonist drug therapies.

PMID- 20807194
TI  - Omalizumab for asthma: indications, off-label uses and future directions.
AB  - Omalizumab is a recombinant humanized monoclonal antibody. Use of omalizumab is
      reported to benefit significantly a subset of asthmatics patients with
      inadequately controlled moderate-to-severe persistent allergic asthma that is not
      controlled with high-dose inhaled corticosteroids. However, recent reports and
      patents suggest wider applications in asthma and related diseases. In this review
      unmet needs and future directions regarding the use of omalizumab in asthma are
      discussed. Better understanding of omalizumab's mechanisms of action on one hand
      and asthma and related pathogenesis on the other hand might contribute to the
      development of better future guidelines of omalizumab use in asthma patients.

PMID- 20807195
TI  - Asp3 mediates multiple protein-protein interactions within the accessory Sec
      system of Streptococcus gordonii.
AB  - Bacterial binding to human platelets is an important step in the pathogenesis of
      infective endocarditis. Streptococcus gordonii can mediate its platelet
      attachment through a cell wall glycoprotein termed GspB ('gordonii surface
      protein B'). GspB export is mediated by a seven-component accessory Sec system,
      containing two homologues of the general secretory pathway (SecA2 and SecY2) and
      five accessory Sec proteins (Asps1-5). Here we show that the Asps are required
      for optimal export of GspB independent of the glycosylation process. Furthermore,
      yeast two-hybrid screening of the accessory Sec system revealed interactions
      occurring between Asp3 and the other components of the system. Asp3 was shown to
      bind SecA2, Asp1, Asp2 and itself. Mutagenesis of Asp3 identified N- and C
      terminal regions that are essential for GspB transport, and conserved residues
      within the C-terminal domain mediated Asp3 binding to other accessory Sec
      components. The loss of binding by Asp3 also resulted in an impaired ability of
      S. gordonii to secrete GspB. These studies indicate that Asp3 is a central
      element mediating multiple interactions among accessory Sec components that are
      essential for GspB transport to the cell surface.

PMID- 20807196
TI  - An essential role for UshA in processing of extracellular flavin electron
      shuttles by Shewanella oneidensis.
AB  - The facultative anaerobe Shewanella oneidensis can reduce a number of insoluble
      extracellular metals. Direct adsorption of cells to the metal surface is not
      necessary, and it has been shown that S. oneidensis releases low concentrations
      flavins, including riboflavin and flavin mononucleotide (FMN), into the
      surrounding medium to act as extracellular electron shuttles. However, the
      mechanism of flavin release by Shewanella remains unknown. We have conducted a
      transposon mutagenesis screen to identify mutants deficient in extracellular
      flavin accumulation. Mutations in ushA, encoding a predicted 5'-nucleotidase,
      resulted in accumulation of flavin adenine dinucleotide (FAD) in culture
      supernatants, with a corresponding decrease in FMN and riboflavin. Cellular
      extracts of S. oneidensis convert FAD to FMN, whereas extracts of ushA mutants do
      not, and fractionation experiments show that UshA activity is periplasmic. We
      hypothesize that S. oneidensis secretes FAD into the periplasmic space, where it
      is hydrolysed by UshA to FMN and adenosine monophosphate (AMP). FMN diffuses
      through outer membrane porins where it accelerates extracellular electron
      transfer, and AMP is dephosphorylated by UshA and reassimilated by the cell. We
      predict that transport of FAD into the periplasm also satisfies the cofactor
      requirement of the unusual periplasmic fumarate reductase found in Shewanella.

PMID- 20807198
TI  - Mutations affecting Leptospira interrogans lipopolysaccharide attenuate
      virulence.
AB  - Leptospira interrogans is the causative agent of leptospirosis.
      Lipopolysaccharide (LPS) is the major outer membrane component of L. interrogans.
      It is the dominant antigen recognized during infection and the basis for
      serological classification. The structure of LPS and its role in pathogenesis are
      unknown. We describe two defined mutants of L. interrogans serovar Manilae with
      transposon insertions in the LPS locus. Mutant M895 was disrupted in gene la1641
      encoding a protein with no known homologues. M1352 was disrupted in a gene unique
      to serovar Manilae also encoding a protein of unknown function. M895 produced
      truncated LPS while M1352 showed little or no change in LPS molecular mass. Both
      mutants showed altered agglutination titres against rabbit antiserum and against
      a panel of LPS-specific monoclonal antibodies. The mutants were severely
      attenuated in virulence via the intraperitoneal route of infection, and were
      cleared from the host animal by 3 days after infection. M895 was also highly
      attenuated via the mucosal infection route. Resistance to complement in human
      serum was unaltered for both mutants. While complementation of mutants was not
      possible, the attenuation of two independently derived LPS mutants demonstrates
      for the first time that LPS plays an essential role leptospiral virulence.

PMID- 20807197
TI  - Importance of the tmRNA system for cell survival when transcription is blocked by
      DNA-protein cross-links.
AB  - Anticancer drug 5-azacytidine (aza-C) induces DNA-protein cross-links (DPCs)
      between cytosine methyltransferase and DNA as the drug inhibits methylation. We
      found that mutants defective in the tmRNA translational quality control system
      are hypersensitive to aza-C. Hypersensitivity requires expression of active
      methyltransferase, indicating the importance of DPC formation. Furthermore, the
      tmRNA pathway is activated upon aza-C treatment in cells expressing
      methyltransferase, resulting in increased levels of SsrA tagged proteins. These
      results argue that the tmRNA pathway clears stalled ribosome-mRNA complexes
      generated after transcriptional blockage by aza-C-induced DPCs. In support, an
      ssrA mutant is also hypersensitive to streptolydigin, which blocks RNA polymerase
      elongation by a different mechanism. The tmRNA pathway is thought to act only on
      ribosomes containing a 3' RNA end near the A site, and the known pathway for
      releasing RNA 3' ends from a blocked polymerase involves Mfd helicase. However,
      an mfd knockout mutant is not hypersensitive to either aza-C-induced DPC
      formation or streptolydigin, indicating that Mfd is not involved. Transcription
      termination factor Rho is also likely not involved, because the Rho-specific
      inhibitor bicyclomycin failed to show synergism with either aza-C or
      streptolydigin. Based on these findings, we discuss models for how E. coli
      processes transcription/translation complexes blocked at DPCs.

PMID- 20807199
TI  - Role of Escherichia coli YbeY, a highly conserved protein, in rRNA processing.
AB  - The UPF0054 protein family is highly conserved with homologues present in nearly
      every sequenced bacterium. In some bacteria, the respective gene is essential,
      while in others its loss results in a highly pleiotropic phenotype. Despite
      detailed structural studies, a cellular role for this protein family has remained
      unknown. We report here that deletion of the Escherichia coli homologue, YbeY,
      causes striking defects that affect ribosome activity, translational fidelity and
      ribosome assembly. Mapping of 16S, 23S and 5S rRNA termini reveals that YbeY
      influences the maturation of all three rRNAs, with a particularly strong effect
      on maturation at both the 5'- and 3'-ends of 16S rRNA as well as maturation of
      the 5'-termini of 23S and 5S rRNAs. Furthermore, we demonstrate strong genetic
      interactions between ybeY and rnc (encoding RNase III), ybeY and rnr (encoding
      RNase R), and ybeY and pnp (encoding PNPase), further suggesting a role for YbeY
      in rRNA maturation. Mutation of highly conserved amino acids in YbeY, allowed the
      identification of two residues (H114, R59) that were found to have a significant
      effect in vivo. We discuss the implications of these findings for rRNA maturation
      and ribosome assembly in bacteria.

PMID- 20807200
TI  - Identification and characterization of two families of F420 H2-dependent
      reductases from Mycobacteria that catalyse aflatoxin degradation.
AB  - Aflatoxins are polyaromatic mycotoxins that contaminate a range of food crops as
      a result of fungal growth and contribute to serious health problems in the
      developing world because of their toxicity and mutagenicity. Although relatively
      resistant to biotic degradation, aflatoxins can be metabolized by certain species
      of Actinomycetales. However, the enzymatic basis for their breakdown has not been
      reported until now. We have identified nine Mycobacterium smegmatis enzymes that
      utilize the deazaflavin cofactor F(420) H(2) to catalyse the reduction of the
      alpha,beta-unsaturated ester moiety of aflatoxins, activating the molecules for
      spontaneous hydrolysis and detoxification. These enzymes belong to two previously
      uncharacterized F(420) H(2) dependent reductase (FDR-A and -B) families that are
      distantly related to the flavin mononucleotide (FMN) dependent pyridoxamine 5'
      phosphate oxidases (PNPOxs). We have solved crystal structures of an enzyme from
      each FDR family and show that they, like the PNPOxs, adopt a split barrel protein
      fold, although the FDRs also possess an extended and highly charged F(420) H(2)
      binding groove. A general role for these enzymes in xenobiotic metabolism is
      discussed, including the observation that the nitro-reductase Rv3547 from
      Mycobacterium tuberculosis that is responsible for the activation of bicyclic
      nitroimidazole prodrugs belongs to the FDR-A family.

PMID- 20807202
TI  - Integrating conjugative elements of the SXT/R391 family trigger the excision and
      drive the mobilization of a new class of Vibrio genomic islands.
AB  - In vibrios and enterobacteria lateral gene transfer is often facilitated by
      integrating conjugative elements (ICEs) of the SXT/R391 family. SXT/R391 ICEs
      integrate by site-specific recombination into prfC and transfer by conjugation, a
      process that is initiated at a specific locus called the origin of transfer
      (oriT(SXT) ). We identified genomic islands (GIs) harbouring a sequence that
      shares >63% identity with oriT(SXT) in three species of Vibrio. Unlike SXT/R391
      ICEs, these GIs are integrated into a gene coding for a putative stress-induced
      protein and do not appear to carry any gene coding for a conjugative machinery or
      for mobilization proteins. Our results show that SXT/R391 ICEs trigger the
      excision and mediate the conjugative transfer in trans of the three Vibrio GIs at
      high frequency. GIs' excision is independent of the ICE-encoded recombinase and
      is controlled by the ICE-encoded transcriptional activator SetCD, which is
      expressed during the host SOS response. Both mobI and traI, two ICE-borne genes
      involved in oriT recognition, are essential for GIs' transfer. We also found that
      SXT/R391 ICEs mobilize in trans over 1 Mb of chromosomal DNA located 5' of the
      GIs' integration site. Together these results support a novel mechanism of
      mobilization of GIs by ICEs of the SXT/R391 family.

PMID- 20807201
TI  - The phage shock protein PspA facilitates divalent metal transport and is required
      for virulence of Salmonella enterica sv. Typhimurium.
AB  - The phage shock protein (Psp) system is induced by extracytoplasmic stress and
      thought to be important for the maintenance of proton motive force. We
      investigated the contribution of PspA to Salmonella virulence. A pspA deletion
      mutation significantly attenuates the virulence of Salmonella enterica serovar
      Typhimurium following intraperitoneal inoculation of C3H/HeN (Ity(r) ) mice. PspA
      was found to be specifically required for virulence in mice expressing the
      natural resistance-associated macrophage protein 1 (Nramp1) (Slc11a1) divalent
      metal transporter, which restricts microbial growth by limiting the availability
      of essential divalent metals within the phagosome. Salmonella competes with
      Nramp1 by expressing multiple metal uptake systems including the Nramp-homologue
      MntH, the ABC transporter SitABCD and the ZIP family transporter ZupT. PspA was
      found to facilitate Mn(2+) transport by MntH and SitABCD, as well as Zn(2+) and
      Mn(2+) transport by ZupT. In vitro uptake of (54) Mn(2+) by MntH and ZupT was
      reduced in the absence of PspA. Transport-deficient mutants exhibit reduced
      viability in the absence of PspA when grown under metal-limited conditions.
      Moreover, the ZupT transporter is required for Salmonella enterica serovar
      Typhimurium virulence in Nramp1-expressing mice. We propose that PspA promotes
      Salmonella virulence by maintaining proton motive force, which is required for
      the function of multiple transporters mediating bacterial divalent metal
      acquisition during infection.

PMID- 20807204
TI  - Shr of group A streptococcus is a new type of composite NEAT protein involved in
      sequestering haem from methaemoglobin.
AB  - A growing body of evidence suggests that surface or secreted proteins with NEAr
      Transporter (NEAT) domains play a central role in haem acquisition and
      trafficking across the cell envelope of Gram-positive bacteria. Group A
      streptococcus (GAS), a beta-haemolytic human pathogen, expresses a NEAT protein,
      Shr, which binds several haemoproteins and extracellular matrix (ECM) components.
      Shr is a complex, membrane-anchored protein, with a unique N-terminal domain
      (NTD) and two NEAT domains separated by a central leucine-rich repeat region. In
      this study we have carried out an analysis of the functional domains in Shr. We
      show that Shr obtains haem in solution and furthermore reduces the haem iron;
      this is the first report of haem reduction by a NEAT protein. More specifically,
      we demonstrate that both of the constituent NEAT domains of Shr are responsible
      for binding haem, although they are missing a critical tyrosine residue found in
      the ligand-binding pocket of other haem-binding NEAT domains. Further
      investigations show that a previously undescribed region within the Shr NTD
      interacts with methaemoglobin. Shr NEAT domains, however, do not contribute
      significantly to the binding of methaemoglobin but mediate binding to the ECM
      components fibronectin and laminin. A protein fragment containing the NTD plus
      the first NEAT domain was found to be sufficient to sequester haem directly from
      methaemoglobin. Correlating these in vitro findings to in vivo biological
      function, mutants analysis establishes the role of Shr in GAS growth with
      methaemoglobin as a sole source of iron, and indicates that at least one NEAT
      domain is necessary for the utilization of methaemoglobin. We suggest that Shr is
      the prototype of a new group of NEAT composite proteins involved in haem uptake
      found in pyogenic streptococci and Clostridium novyi.

PMID- 20807206
TI  - Target transcription binding sites differentiate two groups of MerR-monovalent
      metal ion sensors.
AB  - The evolution of bacterial regulatory circuits often involves duplication of
      genes encoding transcription factors that may suffer both modifications in their
      detected signals, as well as, rewiring of their target operators. This, and
      subsequent horizontal gene transfer events contribute to generate a diverse array
      of regulatory pathways. In Salmonella, two homologous transcription factors CueR
      and GolS are responsible for Cu and Au sensing and resistance respectively. They
      share similarities not only in their sequence but also in their target binding
      sites, although they cluster separately among MerR-monovalent metal sensors.
      Here, we demonstrate that CueR and GolS can selectively distinguish their target
      binding sites by recognizing bases at positions 3' and 3 of their cognate
      operators. Swap of these bases results in switching regulator dependency. The
      differences in promoter architecture plus the environmentally controlled
      regulator's cytoplasmic availability warrant intra-regulon regulator-operator
      selectivity, and the proper response to metal injury. Furthermore, the presence
      of the distinctive operators' bases is widely extended among the two groups of
      MerR-monovalent metal sensors, providing evidence of the co-evolution of these
      factors and their target operators. This approach allows the prediction of
      regulator's dependency and the identification of transcription modules among
      groups of homologous transcription factors.

PMID- 20807203
TI  - Chloroquine susceptibility and reversibility in a Plasmodium falciparum genetic
      cross.
AB  - Mutations in the Plasmodium falciparum chloroquine (CQ) resistance transporter
      (PfCRT) are major determinants of verapamil (VP)-reversible CQ resistance (CQR).
      In the presence of mutant PfCRT, additional genes contribute to the wide range of
      CQ susceptibilities observed. It is not known if these genes influence mechanisms
      of chemosensitization by CQR reversal agents. Using quantitative trait locus
      (QTL) mapping of progeny clones from the HB3 * Dd2 cross, we show that the P.
      falciparum multidrug resistance gene 1 (pfmdr1) interacts with the South-East
      Asia-derived mutant pfcrt haplotype to modulate CQR levels. A novel chromosome 7
      locus is predicted to contribute with the pfcrt and pfmdr1 loci to influence CQR
      levels. Chemoreversal via a wide range of chemical structures operates through a
      direct pfcrt-based mechanism. Direct inhibition of parasite growth by these
      reversal agents is influenced by pfcrt mutations and additional loci. Direct
      labelling of purified recombinant PfMDR1 protein with a highly specific
      photoaffinity CQ analogue, and lack of competition for photolabelling by VP,
      supports our QTL predictions. We find no evidence that pfmdr1 copy number affects
      CQ response in the progeny; however, inheritance patterns indicate that an allele
      specific interaction between pfmdr1 and pfcrt is part of the complex genetic
      background of CQR.

PMID- 20807205
TI  - Nucleoid occlusion prevents cell division during replication fork arrest in
      Bacillus subtilis.
AB  - How bacteria respond to chromosome replication stress has been traditionally
      studied using temperature-sensitive mutants and chemical inhibitors. These
      methods inevitably arrest all replication and lead to induction of
      transcriptional responses and inhibition of cell division. Here, we used
      repressor proteins bound to operator arrays to generate a single stalled
      replication fork. These replication roadblocks impeded replisome progression on
      one arm, leaving replication of the other arm and re-initiation unaffected.
      Remarkably, despite robust generation of RecA-GFP filaments and a strong block to
      cell division during the roadblock, patterns of gene expression were not
      significantly altered. Consistent with these findings, division inhibition was
      not mediated by the SOS-induced regulator YneA nor by RecA-independent repression
      of ftsL. In support of the idea that nucleoid occlusion prevents inappropriate
      cell division during fork arrest, immature FtsZ-rings formed adjacent to the DNA
      mass but rarely on top of it. Furthermore, mild alterations in chromosome
      compaction resulted in cell division that guillotined the DNA. Strikingly, the
      nucleoid occlusion protein Noc had no discernable role in division inhibition.
      Our data indicate that Noc-independent nucleoid occlusion prevents inappropriate
      cell division during replication fork arrest. They further suggest that Bacillus
      subtilis normally manages replication stress rather than inducing a stress
      response.

PMID- 20807208
TI  - Vitronectin in bacterial pathogenesis: a host protein used in complement escape
      and cellular invasion.
AB  - The multifunctional human glycoprotein vitronectin (Vn) plays a significant role
      in cell migration, tissue repair and regulation of membrane attack complex (MAC)
      formation. It also promotes neutrophil infiltration and, thus, enhances the
      inflammatory process during infection. In the host, a balanced homeostasis is
      maintained by Vn due to neutralization of the self-reactivity of the MAC. On the
      other hand, Vn bound to the bacterial surface protects from MAC-mediated lysis
      and enhances adhesion. Gram-negative bacterial pathogens including Moraxella
      catarrhalis, Haemophilus influenzae and Neisseria gonorrhoeae use Vn recruitment
      to prevent MAC deposition at their surface. Moreover, Gram-positive bacterial
      pathogens such as Streptococcus pneumoniae and S. pyogenes utilize Vn for
      effective adhesion to host cells and subsequent internalization. Vitronectin has
      an Arg-Gly-Asp (RGD) sequence for binding the host cell integrin receptors and a
      separate bacterial-binding domain for pathogens, and thus more likely functions
      to cross-link bacteria and epithelial cells. Once bacteria are attached to the
      vitronectin-integrin complex, various host cell-signalling events are activated
      and promote internalization. In this review, we focus on the important roles of
      vitronectin in bacterial pathogenesis and describe different strategies used by
      pathogens to evade the host response by the help of this intriguing molecule.

PMID- 20807207
TI  - The MYST family histone acetyltransferase regulates gene expression and cell
      cycle in malaria parasite Plasmodium falciparum.
AB  - Histone lysine acetylation, normally associated with euchromatin and active
      genes, is regulated by different families of histone acetyltransferases (HATs). A
      single Plasmodium falciparum MYST (PfMYST) HAT was expressed as a long and a
      short version in intraerythrocytic stages. Whereas the recombinant PfMYST
      expressed in prokaryotes and insect cells did not show HAT activity, recombinant
      PfMYST purified from the parasites exhibited a predilection to acetylate histone
      H4 in vitro at K5, K8, K12 and K16. Tagging PfMYST with the green fluorescent
      protein at the C-terminus showed that PfMYST protein was localized in both the
      nucleus and cytoplasm. Consistent with the importance of H4 acetylation in var
      gene expression, PfMYST was recruited to the active var promoter. Attempts to
      disrupt PfMYST were not successful, suggesting that PfMYST is essential for
      asexual intraerythrocytic growth. However, overexpression of the long, active or
      a truncated, non-active version of PfMYST by stable integration of the expression
      cassette in the parasite genome resulted in changes of H4 acetylation and cell
      cycle progression. Furthermore, parasites with PfMYST overexpression showed
      changes in sensitivity to DNA-damaging agents. Collectively, this study showed
      that PfMYST plays important roles in cellular processes such as gene activation,
      cell cycle control and DNA repair.

PMID- 20807209
TI  - The fasciclin-like arabinogalactan protein gene, FLA3, is involved in microspore
      development of Arabidopsis.
AB  - Arabinogalactan proteins are widely distributed in plant tissues and cells, and
      may function in the growth and development of higher plants. To our knowledge,
      there is currently no direct evidence concerning the involvement of fasciclin
      like arabinogalactan proteins (FLA) in sexual reproduction in Arabidopsis. In
      this study, Arabidopsis FLA3 was found to be specifically expressed in pollen
      grains and tubes. Subcellular localization showed that FLA3 anchors tightly to
      the plasma membrane, and its glycosylphosphatidylinositol anchor may affect its
      localization. FLA3-RNA interference transgenic plants had approximately 50%
      abnormal pollen grains (including shrunken and wrinkled phenotypes) which lacked
      viability. Cytological observations revealed that pollen abortion occurred during
      the transition from uninucleate microspores to bicellular pollens, with abnormal
      cellulose distribution seen by calcofluor white staining. Transmission electron
      microscopy showed that the basic structure of the exine layer in aberrant pollen
      was normal, but the intine layer appeared to have some abnormalities. Taken
      together, these results suggest that FLA3 is involved in microspore development
      and may affect pollen intine formation, possibly by participating in cellulose
      deposition. In FLA3-overexpressing transgenic plants, defective elongation of the
      stamen filament and reduced female fertility led to short siliques with low seed
      set, which suggested that ectopic expression of FLA3 in tissues may reduce or
      disrupt cell growth and then result in defects throughout the plant.

PMID- 20807210
TI  - Endogenous overexpression of Populus MYB186 increases trichome density, improves
      insect pest resistance, and impacts plant growth.
AB  - Trichomes are specialized epidermal cells that generally play a role in reducing
      transpiration and act as a deterrent to herbivory. In a screen of activation
      tagged Populus tremula * Populus alba 717-1B4 trees, we identified a mutant line,
      fuzzy, with increased foliar trichome density. This mutant also had a 35%
      increase in growth rate and a 200% increase in the rate of photosynthesis as
      compared with wild-type poplar. The fuzzy mutant had significant resistance to
      feeding by larvae of the white-spotted tussock moth (Orgyia leucostigma), a
      generalist insect pest of poplar trees. The fuzzy trichome phenotype is
      attributable to activation tagging and increased expression of the gene encoding
      PtaMYB186, which is related to Arabidopsis thaliana MYB106, a known regulator of
      trichome initiation. The fuzzy phenotype can be recapitulated by overexpressing
      PtaMYB186 in poplar. PtaMYB186 overexpression results in reconfiguration of the
      poplar transcriptome, with changes in the transcript abundance of suites of genes
      that are related to trichome differentiation. It is notable that a plant with
      misexpression of a gene responsible for trichome development also had altered
      traits related to growth rate and pest resistance, suggesting that non-intuitive
      facets of plant development might be useful targets for plant improvement.

PMID- 20807211
TI  - Elongator subunit 2 is an accelerator of immune responses in Arabidopsis
      thaliana.
AB  - Immune responses in eukaryotes involve rapid and profound transcriptional
      reprogramming. Although mechanisms regulating the amplitude of defense gene
      expression have been extensively characterized, those controlling the speed of
      defense gene induction are not well understood. Here, we show that the
      Arabidopsis Elongator subunit 2 (AtELP2) regulates the kinetics of defense gene
      induction. AtELP2 is required for rapid defense gene induction and the
      establishment of full basal and effector-triggered immunity (ETI). Surprisingly,
      biological or chemical induction of systemic acquired resistance (SAR), a long
      lasting plant immunity against a broad spectrum of pathogens, restores pathogen
      resistance to Atelp2 mutant plants. Simultaneous removal of AtELP2 and NPR1, a
      transcription coactivator essential for full-scale expression of a subset of
      defense genes and the establishment of SAR, completely abolishes resistance to
      two different ETI-inducing pathogens. These results demonstrate that AtELP2 is an
      accelerator of defense gene induction, which functions largely independently of
      NPR1 in establishing plant immunity.

PMID- 20807212
TI  - The DOF transcription factor Dof5.1 influences leaf axial patterning by promoting
      Revoluta transcription in Arabidopsis.
AB  - Dof proteins are transcription factors that have a conserved single zinc finger
      DNA-binding domain. In this study, we isolated an activation tagging mutant
      Dof5.1-D exhibiting an upward-curling leaf phenotype due to enhanced expression
      of the REV gene that is required for establishing adaxial-abaxial polarity.
      Dof5.1-D plants also had reduced transcript levels for IAA6 and IAA19 genes,
      indicating an altered auxin biosynthesis in Dof5.1-D. An electrophoretic mobility
      shift assay using the Dof5.1 DNA-binding motif and the REV promoter region
      indicated that the DNA-binding domain of Dof5.1 binds to a TAAAGT motif located
      in the 5'-distal promoter region of the REV promoter. Further, transient and
      chromatin immunoprecipitation assays verified binding activity of the Dof5.1 DNA
      binding motif with the REV promoter. Consistent with binding assays, constitutive
      over-expression of the Dof5.1 DNA-binding domain in wild-type plants caused a
      downward-curling phenotype, whereas crossing Dof5.1-D to a rev mutant reverted
      the upward-curling phenotype of the Dof5.1-D mutant leaf to the wild-type. These
      results suggest that the Dof5.1 protein directly binds to the REV promoter and
      thereby regulates adaxial-abaxial polarity.

PMID- 20807213
TI  - Pumpkin eIF5A isoforms interact with components of the translational machinery in
      the cucurbit sieve tube system.
AB  - In yeast, eIF5A, in combination with eEF2, functions at the translation step,
      during the protein elongation cycle. This result is of significance with respect
      to functioning of the enucleate sieve tube system, as eIF5A was recently detected
      in Cucurbita maxima (pumpkin) phloem sap. In the present study, we further
      characterized four CmeIF5A isoforms, encoding three proteins, all of which were
      present in the phloem sap. Although hypusination of CmeIF5A was not necessary for
      entry into the sieve elements, this unique post-translational modification was
      necessary for RNA binding. The two enzymes required for hypusination were
      detected in pumpkin phloem sap, where presumably this modification takes place. A
      combination of gel-filtration chromatography and protein overlay assays
      demonstrated that, as in yeast, CmeIF5A interacts with phloem proteins, like
      eEF2, known to be involved in protein synthesis. These findings are discussed in
      terms of a potential role for eIF5A in regulating protein synthesis within the
      enucleate sieve tube system of the angiosperms.

PMID- 20807214
TI  - Durable panicle blast-resistance gene Pb1 encodes an atypical CC-NBS-LRR protein
      and was generated by acquiring a promoter through local genome duplication.
AB  - Rice blast is one of the most widespread and destructive plant diseases
      worldwide. Breeders have used disease resistance (R) genes that mediate fungal
      race-specific 'gene-for-gene' resistance to manage rice blast, but the resistance
      is prone to breakdown due to high pathogenic variability of blast fungus. Panicle
      blast 1 (Pb1) is a blast-resistance gene derived from the indica cultivar
      'Modan'. Pb1-mediated resistance, which is characterized by durability of
      resistance and adult/panicle blast resistance, has been introduced into elite
      varieties for commercial cultivation. We isolated the Pb1 gene by map-based
      cloning. It encoded a coiled-coil-nucleotide-binding-site-leucine-rich repeat (CC
      NBS-LRR) protein. The Pb1 protein sequence differed from previously reported R
      proteins, particularly in the NBS domain, in which the P-loop was apparently
      absent and some other motifs were degenerated. Pb1 was located within one of
      tandemly repeated 60-kb units, which presumably arose through local genome
      duplication. Pb1 transcript levels increased during the development of Pb1+
      cultivars; this expression pattern accounts for their adult/panicle resistance.
      Promoter:GUS analysis indicated that genome duplication played a crucial role in
      the generation of Pb1 by placing a promoter sequence upstream of its coding
      sequence, thereby conferring a Pb1-characteristic expression pattern to a
      transcriptionally inactive 'sleeping' resistance gene. We discuss possible
      determinants for the durability of Pb1-mediated blast resistance.

PMID- 20807215
TI  - Functional specialization within the vacuolar sorting receptor family: VSR1, VSR3
      and VSR4 sort vacuolar storage cargo in seeds and vegetative tissues.
AB  - Two different gene families have been proposed to act as sorting receptors for
      vacuolar storage cargo in plants: the vacuolar sorting receptors (VSRs) and the
      receptor homology-transmembrane-RING H2 domain proteins (RMRs). However,
      functional data on these genes is scarce and the identity of the sorting receptor
      for storage proteins remains controversial. Through a genetic screen we have
      identified the mtv2 mutant, which is defective in vacuolar transport of the
      storage cargo VAC2 in shoot apices. Map-based cloning revealed that mtv2 is a
      loss of function allele of the VSR4 gene. We show that VSR1, VSR3 and VSR4, but
      not the remaining VSRs or RMRs, participate in vacuolar sorting of VAC2 in
      vegetative tissues, and 12S globulins and 2S albumins in seeds, an activity that
      is essential for seedling germination vigor. Finally, we demonstrate that the
      functional diversification in the VSR family results from divergent expression
      patterns and also from distinct sorting activities of the family members.

PMID- 20807216
TI  - Meta-analysis: reduction in hepatic events following interferon-alfa therapy of
      chronic hepatitis B.
AB  - BACKGROUND: The long-term benefit of interferon-alfa (IFN-alpha) treatment in
      preventing various hepatic complications is not certain. AIM: To study the
      effects of IFN-alpha on reducing the risk of developing overall hepatic events
      (hepatocellular carcinoma, cirrhotic complications and liver-related mortality)
      in chronic hepatitis B patients. METHODS: Randomized controlled trials, case
      control studies and cohort studies were retrieved from electronic databases and
      conference abstracts. Relative risks (RRs) of different hepatic complications
      among patients treated by IFN-alpha vs. no treatment or placebo were studied.
      RESULTS: Eleven studies were identified totalling 975 patients treated by IFN
      alpha vs. 1147 untreated controls for analysis. Patients were treated by IFN
      alpha for 1-24 months with a post-treatment follow-up of 1-13 years. Treatment by
      IFN-alpha reduced the risk of overall hepatic events (RR 0.55, 95% confident
      interval or CI 0.43-0.70, P < 0.001) and cirrhotic complications (RR 0.46, 95% CI
      0.32-0.67, P < 0.001) by 45% and 54% respectively. Patients who responded to IFN
      alpha had more profound reduction in overall hepatic events (RR 0.20, 95% CI 0.05
      0.87, P = 0.03) and cirrhotic complications (RR 0.19, 95% CI 0.09-0.38, P <
      0.001) vs. the untreated controls. CONCLUSION: Interferon-alfa treatment reduces
      the risk of hepatic events particularly among responders to treatment.

PMID- 20807218
TI  - Maintenance of clinical benefit in Crohn's disease patients after discontinuation
      of infliximab: long-term follow-up of a single centre cohort.
AB  - BACKGROUND: Tumour necrosis factor-blockade with infliximab has advanced the
      treatment of Crohn's disease. While infliximab is efficacious, it remains to be
      determined whether patients who enter clinical remission with an anti-tumour
      necrosis factor therapy can have their treatment stopped and retain the state of
      remission. AIM: To assess in patients with Crohn's disease who obtained
      infliximab-induced remission, the proportion who relapsed after infliximab
      discontinuation. METHODS: This longitudinal cohort study examined patients from a
      University-based IBD referral centre. Forty eight patients with Crohn's disease
      in full clinical remission and who then discontinued infliximab were followed up
      for up to 7 years. Crohn's disease relapse was defined as an intervention with
      Crohn's disease medication or surgery. RESULTS: Kaplan-Meier analysis of the
      proportion of patients with sustained clinical benefit demonstrated that 50%
      relapsed within 477 days after infliximab discontinuance. In contrast, 35% of
      patients remained well, and without clinical relapse, up to the end of the nearly
      7-year follow-up. CONCLUSIONS: In patients with Crohn's disease with an
      infliximab-induced remission, stopping infliximab results in a predictable
      relapse in a majority of patients. Nevertheless, a small percentage of patients
      sustain a long-term remission.

PMID- 20807219
TI  - Morin (2',3,4',5,7-pentahydroxyflavone) protected cells against gamma-radiation
      induced oxidative stress.
AB  - Ionizing radiation can induce cell damage by generating reactive oxygen species
      (ROS). The present study was carried out to investigate the radio-protective
      effects of a flavonoid compound, morin (2',3,4',5,7-pentahydroxyflavone) and the
      underlying mechanisms. Morin was found to reduce the intracellular ROS generated
      by gamma-irradiation. Moreover, morin protected cellular components against
      radiation-induced membrane lipid peroxidation and cellular DNA damage, which are
      the main targets of radiation-induced cell damage. Morin recovered cell viability
      damaged by radiation via inhibition of apoptosis. Irradiated cells with morin
      treatment reduced Bax, phospho Bcl-2, active caspase 9 and caspase 3, which were
      induced by gamma-radiation. Irradiated cells with morin recovered the expression
      of Bcl-2 reduced by gamma-radiation. Morin exerted anti-apoptotic effects via
      inhibition of mitogen-activated protein kinase kinase-4 (MKK4/SEK1)-c-Jun NH(2) 
      terminal kinase (JNK)-activator protein 1 (AP-1) cascades induced by gamma
      radiation. The results suggest that morin protects cells against oxidative stress
      induced by radiation via reduction of ROS and attenuation of SEK1-JNK-AP-1
      pathway.

PMID- 20807217
TI  - Characterizing abdominal pain in IBS: guidance for study inclusion criteria,
      outcome measurement and clinical practice.
AB  - BACKGROUND: Although irritable bowel syndrome (IBS) is a multisymptom disorder,
      abdominal pain drives illness severity more than other symptoms. Despite
      consensus that IBS trials should measure pain to define study entry and determine
      efficacy, the optimal method of measuring pain remains uncertain. AIM: To
      determine whether combining information from multiple pain dimensions may capture
      the IBS illness experience more effectively than the approach of measuring 'pain
      predominance' or pain intensity alone. METHODS: Irritable bowel syndrome patients
      rated dimensions of pain, including intensity, frequency, constancy,
      predominance, predictability, duration, speed of onset and relationship to bowel
      movements. We evaluated the impact of each dimension on illness severity using
      multivariable regression techniques. RESULTS: Among the pain dimensions,
      intensity, frequency, constancy and predictability were strongly and
      independently associated with illness severity; the other dimensions had weaker
      associations. The clinical definition of 'pain predominance', in which patients
      define pain as their most bothersome symptom, was insufficient to categorize
      patients by illness severity. CONCLUSIONS: Irritable bowel disease pain is
      multifaceted; some pain dimensions drive illness more than others. IBS trials
      should measure various pain dimensions, including intensity, constancy, frequency
      and predictability; this may improve upon the customary use of measuring pain as
      a unidimensional symptom in IBS.

PMID- 20807220
TI  - Observer variability in the application of morphologic and dynamic criteria
      according to the BI-RADS for MRI.

PMID- 20807221
TI  - Quantitative sequence-kinetics relationship in antigen-antibody interaction
      kinetics based on a set of descriptors [corrected].
AB  - The interaction between recombinant Fab57P and the coat protein of tobacco mosaic
      virus was studied using quantitative structure-activity relationship (QSAR)
      method. The development of quantitative multivariate model has shown to be a
      promising approach for unraveling protein-protein interactions by designed
      mutations in peptide sequence. This approach makes it possible to stereo
      chemically determine which residue properties contribute most to the interaction.
      A set of side-chain descriptors was proposed and applied in structural
      characterization of three positions (positions 142, 145 and 146) in the peptide
      antigen. Quantitative sequence-kinetics relationship (QSKR) models describing the
      dissociation rates (log k(d) ) were developed successfully using orthogonal
      signal correction-partial least squares method. The results showed that peptides
      will have high log k(d) values when the amino acids in position 142 and 145 have
      high net charge index, and when residue 145 has high hydrophobicity and residue
      146 has low hydrophobicity.

PMID- 20807222
TI  - Synthetic peptide vaccine development: designing dual epitopes into a single
      pilin peptide immunogen generates antibody cross-reactivity between two strains
      of Pseudomonas aeruginosa.
AB  - One of the main challenges of Pseudomonas aeruginosa vaccine development is the
      design of an antigen that elicits cross-reactive antibodies against multiple
      virulent strains. Using a rational design approach, we have developed a single 17
      residue peptide immunogen that generates antibodies that target the receptor
      binding domain of the type IV pilus of more than one strain of P. aeruginosa.
      Using the receptor-binding domain sequence, of native strain PAO as a template,
      we have systematically changed up to five residues in the PAO sequence of the
      peptide immunogen into that of the PAK sequence. We show by indirect and
      competitive ELISA that the mutant peptide immunogens elicit the development of
      polyclonal sera that is cross-reactive to both native strain PAO and PAK pilin.
      We further show that there are at least two separate antibody populations in the
      polyclonal sera that possess closely related epitopes but which are each strain
      specific. Moreover, part of the epitope for the PAO-specific antibodies consists
      of several residues outside the disulfide loop of the receptor-binding domain.
      This allows us to create two unique epitopes within the same receptor-binding
      domain sequence.

PMID- 20807223
TI  - Disruption of the SCN2A and SCN3A genes in a patient with mental retardation,
      neurobehavioral and psychiatric abnormalities, and a history of infantile
      seizures.
AB  - Mutations in genes encoding voltage-gated sodium channels are significant factors
      in the etiology of neurological diseases and psychiatric disorders, including
      various types of idiopathic epilepsy. Using a clinical exon-targeted
      oligonucleotide array comparative genomic hybridization (aCGH), we have
      identified a de novo ~110-kb deletion involving exons 1-2 of SCN2A and non-coding
      exon 1a of SCN3A in a 25-year-old female with mental retardation, neurobehavioral
      and psychiatric abnormalities, and a history of infantile seizures with abnormal
      EEG. We propose that haploinsufficiency of SCN2A may play an important role in
      the genetic basis of neurodevelopmental and neurobehavioral disorders and
      emphasize the efficacy of detecting exonic copy-number variation (CNV) by exon
      targeted oligo aCGH.

PMID- 20807224
TI  - New mutations in ZFPM2/FOG2 gene in tetralogy of Fallot and double outlet right
      ventricle.
AB  - Conotruncal defects (CTDs) represent 15-20% of all congenital heart defects.
      Mutations in a number of genes have been associated with CTD in humans and animal
      models. We investigated the occurrence and the prevalence of GATA4, NKX2.5,
      ZFPM2/FOG2, GDF1, and ISLET1 gene mutations in a large cohort of individuals with
      CTD, including tetralogy of Fallot with or without pulmonary atresia (TOF, 178
      patients), double outlet right ventricle (DORV, 13 patients), and truncus
      arteriosus (11 patients). Denaturing high-performance liquid chromatography
      (DHPLC) analysis followed by bidirectional sequencing disclosed no putative
      pathogenic mutation in GATA4, ISLET1, and GDF1 genes. Two novel (Ile227Val,
      Met544Ile) and one previously reported (Glu30Gly) possibly pathogenic missense
      variants were identified in the ZFPM2/FOG2 gene in 3 sporadic patients of 202
      (1.5%) with CTD, including 1 of 178 (0.6%) with TOF and 2 of 13 (15.4%) with
      DORV. Mutation analysis also detected one known missense change (Arg25Cys) in
      NKX2.5 gene in two (1.1%) sporadic patients with TOF. These sequence alterations
      were found to be absent in 500 population-matched controls. In conclusion, the
      present results (i) indicate and confirm that mutations in the GATA4, GDF1, and
      ISLET1 genes are not major determinants in the pathogenesis of TOF, (ii) provide
      supportive evidence of an association between ZFPM2/FOG2 gene and TOF/DORV, and
      (iii) provide additional examples of the possible contribution of the Arg25Cys
      change in the NKX2.5 to a small number of TOF cases.

PMID- 20807225
TI  - Clinical impact of a highly prevalent Pseudomonas aeruginosa clone in Dutch
      cystic fibrosis patients.
AB  - Studies suggest that infection with highly prevalent Pseudomonas aeruginosa
      clones in cystic fibrosis (CF) is associated with an unfavourable clinical
      outcome. We studied the clinical characteristics of patients infected with a
      recently described, highly prevalent P. aeruginosa clone (ST406) in two CF
      centres in The Netherlands. Multilocus sequence typing data were available for
      219 patients, of whom 40 (18.3%) were infected with ST406 and 179 with other
      sequence types. ST406 infection was independently associated with age, having a
      sibling with ST406 infection and use of inhaled antibiotics, but not with
      unfavourable clinical outcome, suggesting that high transmissibility is not
      necessarily associated with high virulence.

PMID- 20807226
TI  - Cause-specific long-term mortality rates in patients recovered from community
      acquired pneumonia as compared with the general Dutch population.
AB  - Insights into long-term mortality, especially into the cause of death after
      initial recovery from an episode of community-acquired pneumonia (CAP), may help
      in determining optimal preventive measures in such patients. Prospective
      observational cohort studies were conducted to compare cause-specific long-term
      mortality rates for 356 patients who had recovered from CAP with those of the
      general Dutch population (16.3 million) between 2003 and 2007. The Dutch
      Municipal Public Records Database and death certificates were used to determine
      cause-specific mortality rates up to 7 years after discharge. In patients who had
      recovered from CAP, cumulative 1-year, 5-year and 7-year mortality rates were
      17%, 43% and 53%, respectively, as compared with 4%, 19% and 24% for an age
      matched and sex-matched population reference cohort. Overall, patients who had
      recovered from CAP had significantly higher long-term mortality than matched
      population controls (rate ratio (RR) 3.6; p <0.001). In the years after an
      episode of CAP, malignancy (27%), chronic obstructive pulmonary disease (COPD)
      (19%) and cardiovascular disease (16%) were the most frequent causes of death.
      Only 6% died of pneumonia, as compared with 3.2% in the general population. After
      initial recovery from an episode of CAP, long-term mortality rates are more than
      three times as high as in the general population. The causes of long-term
      mortality were mostly comorbidity-related, and significantly different from those
      in the general population. After an episode of CAP, optimization of treatment of
      comorbidities, such as treatment for COPD, might improve long-term survival
      rates.

PMID- 20807227
TI  - Surface EMG characteristics of people with multiple sclerosis during static
      contractions of the knee extensors.
AB  - OBJECTIVES: This study was designed to determine whether any alterations existed
      in surface electromyography (sEMG) in people with multiple sclerosis (MS) during
      isometric contractions of the knee extensors. METHODS: Fifteen people with MS and
      14 matched controls (mean +/- SD age and body mass index 53.7 +/- 10.5 versus
      54.6 +/- 9.6 years and 27.7 +/- 6.1 versus 26.5 +/- 4, respectively) completed
      20%, 40%, 60% and 80% of their maximal voluntary contraction (MVC) of the knee
      extensors. sEMG was recorded from the vastus lateralis where muscle fibre
      conduction velocity (MFCV) and sEMG amplitude (RMS) were assessed. Body
      composition was determined using dual-energy X-ray absorptiometry and physical
      activity with the use of accelerometry. RESULTS: People with MS showed
      significantly (P<0.05) faster MFCV during MVC (6.6 +/- 2.7 versus 4.7 +/- 1.4 m
      s(-1) ) and all submaximal contractions, while RMS was significantly (P<0.05)
      less (0.11 +/- 0.03 versus 0.24 +/- 0.06 mV) in comparison with the controls. MVC
      along with specific thigh lean mass to torque, rate of force development and mean
      physical activity were significantly (P<0.01) less in PwMS. CONCLUSION: People
      with MS have elevated MFCV alongside reduced RMS during isometric contraction.
      This elevation in MFCV should be accounted for when interpreting sEMG from people
      with MS.

PMID- 20807228
TI  - Determinants of the reduction in B-type natriuretic peptide after mitral valve
      replacement in patients with rheumatic mitral stenosis.
AB  - BACKGROUND: Plasma B-type natriuretic peptide (BNP) levels are closely related to
      symptoms in left ventricle (LV) systolic heart failure, although marked regarding
      heterogeneity levels among subjects are reported. AIMS: To assess the influence
      of right ventricle on plasma BNP in the patients with different grades of its
      overload secondary to severe mitral valve stenosis (MVS). METHODS: Plasma BNP was
      evaluated in MVS patients (n = 27) before valve replacement and during follow-up
      (FUV) 401 +/- 42 days after operation. RESULTS: Initial examination showed severe
      MVS (0.9 +/- 0.2 cm2), left atrial enlargement (LAI 30 +/- 4.5 mm m-2), right
      ventricle diastolic dilatation (RVDI 16 +/- 3.6 mm m-2), normal LV size/function
      and elevated BNP levels (166 +/- 137 pg ml-1). FUV examination revealed a
      significant reduction in LAI (27 +/- 2.2 mm m-2), RVDI (14 +/- 1.6 mm m-2) and
      BNP levels (80 +/- 35 pg ml-1). The regression analysis of the initial parameters
      found RVDI to be the strongest predictor (R2 = 0.61; P<0.0001) for BNP level,
      whereas RVDI reduction was the strongest factor for BNP decrease (R2 = 0.65;
      P<0.0001) during FUV. CONCLUSIONS: Right ventricle should be taken into account
      as a potential important source of plasma BNP owing to the fact that LV size and
      function are well preserved in MVS patients. RVDI determines BNP plasma levels
      whereas after MVS removal, the RVDI reduction predicts BNP level decrease.

PMID- 20807229
TI  - The effects of in vitro hemodilution with 6% hydroxyethyl starch (HES) (130/0.4)
      solution on thrombelastograph analysis in patients undergoing liver
      transplantation.
AB  - INTRODUCTION: The aim of this study was to determine the effects of in vitro
      hemodilution with 6% HES (130/0.4) solution on thrombelastograph((r)) (TEG)
      parameters in whole blood samples from patients with end-stage liver disease
      (ESLD). METHODS:   Enrollment consisted of 95 patients with ESLD undergoing liver
      transplantation. Blood was diluted by 11%, 22%, and 33% with 6% HES (130/0.4)
      solution. Normal saline was used as a control diluent. RESULTS: When blood was
      diluted by 33% with normal saline, only the reaction time (r) was increased (p <
      0.0001) compared to the baseline value. When blood was diluted with 6% HES
      (130/0.4), 11% dilution decreased maximum amplitude (MA) (p = 0.003) compared to
      baseline. At 33% dilution, the r (p < 0.0001, vs. baseline) and K (p < 0.0001,
      vs. baseline; p < 0.0001, vs. normal saline) increased, and the MA, alpha angle,
      and coagulation index (p < 0.0001, vs. baseline; p < 0.0001, vs. normal saline)
      decreased. CONCLUSION: Hemodilution with 6% HES (130/0.4) solution results in TEG
      abnormalities even with 11% hemodilution, in whole blood samples of patients with
      ESLD undergoing liver transplantation.

PMID- 20807230
TI  - A question of justice: assessing nurse migration from a philosophical
      perspective.
AB  - The intensified nurse migration leads to severe problems for the health care
      systems in many developing countries. Using the Philippines as an example, this
      paper will address the question of global nurse migration from a philosophical
      perspective. John Rawls' liberal and Michael Walzer's communitarian theory of
      justice will be examined in view of the ethical problem of nurse migration. In
      line with Rawls' A Theory of Justice, nurse migration undermines the ability of
      the people in developing countries to make use of their basic rights and
      liberties. Walzer's communitarian assessment of nurse migration, on the other
      hand, will stress the shared 'thin' morality, as well as the shared history
      between the 'donating' and receiving countries. This paper argues that the
      commonality of a shared history and common values implies the moral obligation to
      ensure a fairer distribution of nurses.

PMID- 20807231
TI  - Serum soluble E-cadherin is a potential prognostic marker in esophageal squamous
      cell carcinoma.
AB  - E-cadherin is a well-documented tumor suppressor with downregulated expression in
      many cancer types. Upon proteolytic cleavage, a soluble form of 80-kDa
      degradation fragment, known as soluble E-cadherin (s-Ecad), is present in
      circulation; its level in sera of cancer patients is significantly associated
      with metastasis, recurrence, and prognosis in some malignancies. The present
      study investigated the association of s-Ecad with clinicopathological
      characteristics of patients with esophageal squamous cell carcinoma (ESCC) and
      its prognostic significance. A cohort of 97 patients who underwent surgery alone
      (n= 56) or neoadjuvant chemoradiation therapy and surgery (CRT) (n= 41) was
      recruited for this study. Serum samples were collected at operation (surgery
      group) and pre- and post-CRT treatment (CRT group) for measurement of s-Ecad
      protein by enzyme linked immunosorbent assay. Serum s-Ecad levels were correlated
      with clinicopathological parameters as well as survival. Univariate analysis
      showed no significant relationship between serum s-Ecad level and
      clinicopathological parameters for all sets of samples. Survival analysis showed
      that in patients who had surgical resection only, those with s-Ecad levels equal
      to or below the median value survived significantly longer than those with levels
      above the median (median survival 25.6 vs. 14.1 months, P= 0.012). Multivariate
      analysis showed that pathological N stage, M stage, R category, and serum s-Ecad
      level were significant independent prognostic factors for ESCC patients who
      underwent surgery only. The hazard ratio for s-Ecad was 1.104 (95% CI: 1.026
      1.187) and P= 0.008. Serum s-Ecad was detected in ESCC patients and its potential
      as an independent prognostic marker requires further investigation.

PMID- 20807232
TI  - Decoupled leaf and stem economics in rain forest trees.
AB  - Cross-species analyses of plant functional traits have shed light on factors
      contributing to differences in performance and distribution, but to date most
      studies have focused on either leaves or stems. We extend these tissue-specific
      analyses of functional strategy towards a whole-plant approach by integrating
      data on functional traits for 13 448 leaves and wood tissues from 4672 trees
      representing 668 species of Neotropical trees. Strong correlations amongst traits
      previously defined as the leaf economics spectrum reflect a tradeoff between
      investments in productive leaves with rapid turnover vs. costly physical leaf
      structure with a long revenue stream. A second axis of variation, the 'stem
      economics spectrum', defines a similar tradeoff at the stem level: dense wood vs.
      high wood water content and thick bark. Most importantly, these two axes are
      orthogonal, suggesting that tradeoffs operate independently at the leaf and at
      the stem levels. By simplifying the multivariate ecological strategies of
      tropical trees into positions along these two spectra, our results provide a
      basis to improve global vegetation models predicting responses of tropical
      forests to global change.

PMID- 20807233
TI  - Tropical forests are not flat: how mountains affect herbivore diversity.
AB  - Ecologists debate whether tropical insect diversity is better explained by higher
      plant diversity or by host plant species specialization. However, plant-herbivore
      studies are primarily based in lowland rainforests (RF) thus excluding
      topographical effects on biodiversity. We examined turnover in Eois (Geometridae)
      communities across elevation by studying elevational transects in Costa Rica and
      Ecuador. We found four distinct Eois communities existing across the elevational
      gradients. Herbivore diversity was highest in montane forests (MF), whereas host
      plant diversity was highest in lowland RF. This was correlated with higher
      specialization and species richness of Eois/host plant species we found in MF.
      Based on these relationships, Neotropical Eois richness was estimated to range
      from 313 (only lowland RF considered) to 2034 (considering variation with
      elevation). We conclude that tropical herbivore diversity and diet breadth covary
      significantly with elevation and urge the inclusion of montane ecosystems in host
      specialization and arthropod diversity estimates.

PMID- 20807234
TI  - Amyloid in skin and brain: what's the link?
AB  - For too long, amyloids have been under general suspicion to merely cause
      diseases. In recent years, we have learned that these interesting proteins may
      also fulfill important biological tasks. Moreover, recent publications show
      emerging evidence for a so-called brain-skin axis. This viewpoint paper aims to
      address the question what is known about the link between brain and skin based on
      the literature available for two diseases caused by amyloid formation:
      Alzheimer's disease (AD) and cutaneous amyloidoses. In addition, we acquaint the
      reader with a different perspective on the role of amyloid in skin and brain.

PMID- 20807235
TI  - Proteomic mining in the dysplastic liver of WHV/c-myc mice--insights and
      indicators for early hepatocarcinogenesis.
AB  - Because of the asymptomatic process of carcinogenesis, the early detection of
      cancers such as hepatocellular carcinoma (HCC) is very challenging. Tumor-prone
      transgenic mouse models of oncogenesis can provide a stable and powerful tool for
      the analysis of cancer initiation, and are therefore promising for the discovery
      of early putative biomarkers of HCC. Using a label-free proteomic quantification
      strategy, we comprehensively investigated the protein expression profile in the
      livers of three 2-month-old WHV/c-myc mice at the dysplastic stage, with age
      matched wt-C57 mice as controls. We identified 2781 proteins, 540 of which were
      differentially expressed. These proteins successfully characterized certain
      precancerous biological processes and alterations in transcriptional regulators
      before tumor onset. Two candidates, FK506-binding protein 4 (FKBP52) and ferritin
      heavy chain, were taken as examples for a search from the mouse model to clinical
      human tissues. Their levels in serum samples were determined by western blotting,
      and showed a noteworthy ability to distinguish between HCC and control cases.
      Immunohistochemical analysis with tissue microarrays confirmed the differential
      expression of FKBP52 between HCC and the paired controls (P < 0.001). The
      regulation of FKBP52 was also discovered to be relevant to HCC staging, with a
      dramatic decline at stage III (P < 0.05). The potentials of the candidate pool in
      this study were discussed in terms of delineating c-myc-induced
      hepatocarcinogenesis and facilitating biomarker discovery for early HCC
      diagnosis.

PMID- 20807236
TI  - Assessing adhesion, biofilm formation and motility of Acidovorax citrulli using
      microfluidic flow chambers.
AB  - Acidovorax citrulli is the causal agent of bacterial fruit blotch of cucurbits.
      We have shown previously that type IV pili (TFP) are required for wild-type
      levels of virulence of A. citrulli on melon and that this pathogen can colonize
      and move thorough the xylem vessels of host seedlings. Here, comparative studies
      between wild-type and TFP mutant strains using microfluidic flow chambers
      demonstrated that TFP play a critical role in both the surface attachment and the
      biofilm formation of A. citrulli under a medium flow. Additionally, TFP null
      mutants were unable to perform twitching movement against the direction of medium
      flow. Assays using a flagellin mutant showed that, in contrast to TFP, polar
      flagella do not contribute to the adhesion and biofilm formation of A. citrulli
      under tested conditions. Also, flagellum-mediated swimming motility of wild-type
      strains was not observed under medium flow. These results imply that TFP may play
      an important role in colonization and spread in the xylem vessels under sap flow
      conditions, while polar flagella could be more important for spread during
      periods of time when xylem flow is minimal.

PMID- 20807237
TI  - Involvement of extracytoplasmic function sigma factors in virulence regulation in
      Porphyromonas gingivalis W83.
AB  - Extracytoplasmic function (ECF) sigma factors are known to play an important role
      in the bacterial response to various environmental stresses and can significantly
      modulate their pathogenic potential. In the genome of Porphyromonas gingivalis
      W83, six putative ECF sigma factors were identified. To further evaluate their
      role in this organism, a PCR-based linear transformation method was used to
      inactivate five ECF sigma factor genes (PG0162, PG0214, PG0985, PG1660, and
      PG1827) by allelic exchange mutagenesis. All five isogenic mutants formed black
      pigmented colonies on blood agar. Mutants defective in PG0985, PG1660, and PG1827
      genes were more sensitive to 0.25 mM of hydrogen peroxide compared with the wild
      type strain. Isogenic mutants of PG0162 and PG1660 showed a 50% decrease in
      gingipain activity. Reverse transcription-PCR analysis showed that there was no
      alteration in the expression of rgpA, rgpB, and kgp gingipain genes in these
      mutants. Hemolytic and hemagglutination activities were decreased by more than
      50% in the PG0162 mutant compared with the wild type. Taken together, these
      findings suggest that ECF sigma factors can modulate important virulence factors
      in P. gingivalis. ECF sigma factors encoded by the PG0162 and PG1660 genes might
      also be involved in the post-transcriptional regulation of the gingipains.

PMID- 20807238
TI  - Correlations between the role, sequence conservation, genomic location and
      severity of phenotype in myxobacterial developmental genes.
AB  - Myxobacterial development requires the coordinated action of both intracellular
      and intercellular signalling pathways. A dataset of myxobacterial developmental
      gene properties suggests that genes encoding components of intracellular pathways
      tend to be less conserved, yield less severe phenotypes upon deletion and lie
      closer to the chromosomal origin than intercellular signalling genes. It would
      seem that there is a stronger negative selection affecting the mutation of
      intercellular signalling pathway genes than intracellular genes. Presumably, this
      is because the loss of social behaviour (and consequently sporulation) upon
      mutation of an intercellular gene is profoundly detrimental to the perpetuation
      of the organism. Conversely, mutation of an intracellular gene would typically
      result in a socially capable mutant. The correlations presented here between the
      severity of phenotype, genomic location and the degree of sequence conservation
      should aid rational exploration of the genomics of social development in the
      myxobacteria.

PMID- 20807239
TI  - Genetic factors of reaction time performance: DRD4 7-repeat allele associated
      with slower responses.
AB  - Twin studies indicate substantial inherited components in cognitive abilities.
      One of the most extensively studied candidate genes of cognitive functioning is
      the dopamine D4 receptor gene (DRD4), which has been suggested to be related to
      attentional disorders. Based on reaction time data of 245 Caucasians
      participating in different cognitive tasks, slower responses characterized the
      group with the 7-repeat allele. This effect was present in both sexes and was not
      because of fatigue. To our knowledge, this is the first report on significant
      association (P = 0.0001) between the DRD4 variable number of tandem repeat (VNTR)
      polymorphism and response latencies in a non-clinical adult sample. Other studied
      dopaminergic polymorphisms did not show an association with reaction time. These
      results illustrate that speed-of-performance measures derived from multiple
      reaction time tasks using standardization procedures could be promising tools to
      detect unique genetic effects in the background of cognitive abilities.

PMID- 20807241
TI  - Accumbens Homer2-mediated signaling: a factor contributing to mouse strain
      differences in alcohol drinking?
AB  - Alcohol-induced increases in nucleus accumbens glutamate actively regulate
      alcohol consumption, and the alcohol responsiveness of corticoaccumbens glutamate
      systems relates to genetic variance in alcohol reward. Here, we extend earlier
      data for inbred mouse strain differences in accumbens glutamate by examining for
      differences in basal and alcohol-induced changes in the striatal expression of
      glutamate-related signaling molecules between inbred C57BL/6J and DBA2/J mice.
      Repeated alcohol treatment (8 * 2 g/kg) increased the expression of Group1
      metabotropic glutamate receptors, the NR2a/b subunits of the N-methyl-D-aspartate
      receptor, Homer2a/b, as well as the activated forms of protein kinase C (PKC)
      epsilon and phosphoinositol-3-kinase within ventral, but not dorsal, striatum.
      Regardless of prior alcohol experience, C57BL/6J mice exhibited higher accumbens
      levels of mGluR1/5, Homer2a/b, NR2a and activated kinases vs. DBA2/J mice,
      whereas an alcohol-induced rise in dorsal striatum mGluR1/5 expression was
      observed only in C57BL/6J mice. We next employed virus-mediated gene transfer
      approaches to ascertain the functional relevance of the observed strain
      difference in accumbens Homer2 expression for B6/D2 differences in alcohol
      induced glutamate sensitization, as well as alcohol preference/intake.
      Manipulating nucleus accumbens shell Homer2b expression actively regulated these
      measures in C57BL/6J mice, whereas DBA2/J mice were relatively insensitive to the
      neurochemical and behavioral effects of virus-mediated changes in Homer2
      expression. These data support the over-arching hypothesis that augmented
      accumbens Homer2-mediated glutamate signaling may be an endophenotype related to
      genetic variance in alcohol consumption. If relevant to humans, such data pose
      polymorphisms affecting glutamate receptor/Homer2 signaling in the etiology of
      alcoholism.

PMID- 20807242
TI  - Ratio and associated factors of dry mouth among community-dwelling elderly
      Japanese women.
AB  - AIM: Dry mouth is one of the common complaints of elderly people, and can
      accompany various disorders. The aim of this study was to investigate the ratio
      of subjective feelings of dry mouth and associated factors of it in Japanese
      community- dwelling elderly women. METHODS: A cross-sectional study was
      conducted. The subjects were 1286 women aged 75-84 years who participated in a
      comprehensive geriatric health examination, including a face-to-face interview,
      questionnaires, and medical and dental examinations. The chi2-test, Student's t
      test and Mann-Whitney U-test were used to compare the differences between the dry
      mouth and normal groups, and multiple logistic regression analyses were performed
      to examine the factors associated with dry mouth. RESULTS: The mean age of the
      participants was 78.4+/-2.7 years and the ratio of dry mouth was 38.8% (n=499).
      According to multiple logistic regression analysis, a history of heart disease
      (odds ratio [OR]=1.46, 95% confidence intervals [CI]=1.01-1.96), the use of anti
      inflammatory drugs and analgesics (OR=1.43, CI=1.00-2.05), a social role
      (OR=0.59, CI=0.39-0.89), difficulty in mastication (OR=1.70, CI=1.32-2.20) and
      difficulty in swallowing (OR=2.18, CI=1.65-2.88) were significantly associated
      with dry mouth. CONCLUSION: The present study suggests that factors associated
      with dry mouth are oral dysfunction such as mastication and swallowing, presence
      of heart disease, use of anti-inflammatory drugs and analgesics, and a social
      role in Japanese community-dwelling elderly women.

PMID- 20807240
TI  - Congenic strains provide evidence that a mapped locus on chromosome 15 influences
      excitotoxic cell death.
AB  - Inbred strains of mice differ in their susceptibility to excitotoxin-induced cell
      death, but the genetic basis of individual variation is unknown. Prior studies
      with crosses of the FVB/NJ (seizure-induced cell death susceptible) mouse and the
      seizure-induced cell death resistant mouse, C57BL/6J, showed the presence of
      three quantitative trait loci (QTLs), named seizure-induced cell death 1 (Sicd1)
      to Sicd3. To better localize and characterize the Sicd2 locus, two reciprocal
      congenic mouse strains were created. While the B6.FVB-Sicd2 congenic mouse was
      without effect on modifying susceptibility to seizure-induced excitotoxic cell
      death, the FVB.B6-Sicd2 congenic mouse, in which the chromosome (Chr) 15 region
      of C57BL/6J was introgressed into FVB/NJ, showed reduced seizure-induced
      excitotoxic cell death following kainate administration. Phenotypic comparison
      between FVB and the congenic FVB.B6-Sicd2 strain confirmed that the Sicd2
      interval harbors gene(s) conferring strong protection against seizure-induced
      excitotoxic cell death. Interval-specific congenic lines (ISCLs) that encompass
      Sicd2 on Chr 15 were generated and were used to fine-map this QTL. Resultant
      progeny were treated with kainate and examined for the extent of seizure-induced
      cell death in order to deduce the Sicd2 genotypes of the recombinants through
      linkage analysis. All of the ISCLs exhibited reduced cell death associated with
      the C57BL/6J phenotype; however, ISCL-2 showed the most dramatic reduction in
      seizure-induced cell death in both area CA3 and in the dentate hilus. These
      findings confirm the existence of polymorphic loci within the reduced critical
      region of Sicd2 that regulate the severity of seizure-induced cell death.

PMID- 20807244
TI  - A model to simulate pumping tests in wells with high loss and backflow.
AB  - Traditional methods of analyzing pumping tests in single wells fail when the well
      loss is very high due to a low transmissivity skin. Because of the restricted
      rate at which water can enter a high loss well from the aquifer, well casing
      storage becomes a significant factor. Additionally, if a slug of water enters the
      well from the pump column immediately after the pump is switched off, it has a
      long-lasting significant effect on the recovering water level in the well because
      it cannot be absorbed rapidly by the aquifer. A theoretical model is derived here
      that simulates the water level in a well in these circumstances. In the model,
      the continuously changing rate of water inflow from the aquifer to the well is
      approximated by a step function with a finite difference time step. It is
      demonstrated by a real example that the model can be applied easily to analyze
      pumping tests, including tests with a varying pumping rate. The analysis confirms
      suspected high well loss, calculates the unknown rate of backflow, and determines
      the aquifer's transmissivity.

PMID- 20807243
TI  - Frontal Assessment Battery and brain perfusion images in amnestic mild cognitive
      impairment.
AB  - AIM: Some patients with mild cognitive impairment (MCI) may have impaired frontal
      lobe function. To assess the frontal lobe functions of subjects with MCI using
      the Frontal Assessment Battery (FAB) and to identify the brain regions
      responsible for FAB performance. METHODS: Based on the FAB score cut-off of
      12/13, 38 MCI subjects were divided into a high FAB group (n=20) and a low FAB
      group (n=18). They underwent single photon emission computed tomography (SPECT)
      and we analyzed the data by the 3-D stereotactic surface projection method.
      RESULTS: No significant differences in neuropsychological tests including memory,
      language and praxis, and depression scores were found between high and low FAB
      groups. Although both groups showed decreases in the regional cerebral blood flow
      (rCBF) of the parietotemporal and frontal regions, the low FAB group demonstrated
      significant decreases in the rCBF of the left lateral frontal and right medial
      frontal regions compared with the high FAB group. CONCLUSION: Our results
      indicate that some patients with amnestic MCI have frontal lobe dysfunction,
      assessed by the FAB. SPECT study suggests that the FAB mainly reflects the
      function of some regions of the left lateral frontal and right medial frontal
      areas.

PMID- 20807245
TI  - Investigation of small-scale preferential flow with a forced-gradient tracer
      test.
AB  - A new tracer experiment (referred to as MADE-5) was conducted at the well-known
      Macrodispersion Experiment (MADE) site to investigate the influence of small
      scale mass-transfer and dispersion processes on well-to-well transport. The test
      was performed under dipole forced-gradient flow conditions and concentrations
      were monitored in an extraction well and in two multilevel sampler (MLS) wells
      located at 6, 1.5, and 3.75 m from the source, respectively. The shape of the
      breakthrough curve (BTC) measured at the extraction well is strongly asymmetric
      showing a rapidly arriving peak and an extensive late-time tail. The BTCs
      measured at seven different depths in the two MLSs are radically different from
      one another in terms of shape, arrival times, and magnitude of the concentration
      peaks. All of these characteristics indicate the presence of a complex network of
      preferential flow pathways controlling solute transport at the test site. Field
      experimental data were also used to evaluate two transport models: a stochastic
      advection-dispersion model (ADM) based on conditional multivariate Gaussian
      realizations of the hydraulic conductivity field and a dual-domain single-rate
      (DDSR) mass-transfer model based on a deterministic reconstruction of the aquifer
      heterogeneity. Unlike the stochastic ADM realizations, the DDSR accurately
      predicted the magnitude of the concentration peak and its arrival time (within a
      1.5% error). For the multilevel BTCs between the injection and extraction wells,
      neither model reproduced the observed values, indicating that a high-resolution
      characterization of the aquifer heterogeneity at the subdecimeter scale would be
      needed to fully capture 3D transport details.

PMID- 20807246
TI  - Porosity and permeability in ternary sediment mixtures.
AB  - Permeability, k, and porosity, phi, were measured in mixtures of fine, medium,
      and coarse sand, where the volume fraction of each of the three components was
      systematically varied. The k was modeled well by the Kozeny-Carman equation for
      three-component mixtures by using a representative grain size parameter, d,
      computed by averaging the grain diameters of components recursively, with
      averaging methods based on whether finer components exist in sufficient volume to
      fill the pores within coarser components. The phi was modeled well by using
      linear interpolation with piecewise-planar models. We explored the use of
      differing numbers of piecewise-planar elements in the model, and illustrate the
      trade-off between the increased accuracy and the increased data requirements that
      both come from adding more elements. The k model is a function of both d and phi,
      but more sensitive to d. The k model gave results consistent with measured values
      when computed using either measured phi values, or values from any of the phi
      models.

PMID- 20807247
TI  - Factors governing sustainable groundwater pumping near a river.
AB  - The objective of this paper was to provide new insights into processes affecting
      riverbank filtration (RBF). We consider a system with an inflatable dam installed
      for enhancing water production from downstream collector wells. Using a numerical
      model, we investigate the impact of groundwater pumping and dam operation on the
      hydrodynamics in the aquifer and water production. We focus our study on two
      processes that potentially limit water production of an RBF system: the
      development of an unsaturated zone and riverbed clogging. We quantify river
      clogging by calibrating a time-dependent riverbed permeability function based on
      knowledge of pumping rate, river stage, and temperature. The dynamics of the
      estimated riverbed permeability reflects clogging and scouring mechanisms. Our
      results indicate that (1) riverbed permeability is the dominant factor affecting
      infiltration needed for sustainable RBF production; (2) dam operation can
      influence pumping efficiency and prevent the development of an unsaturated zone
      beneath the riverbed only under conditions of sufficient riverbed permeability;
      (3) slow river velocity, caused by dam raising during summer months, may lead to
      sedimentation and deposition of fine-grained material within the riverbed, which
      may clog the riverbed, limiting recharge to the collector wells and contributing
      to the development of an unsaturated zone beneath the riverbed; and (4) higher
      river flow velocities, caused by dam lowering during winter storms, scour the
      riverbed and thus increase its permeability. These insights can be used as the
      basis for developing sustainable water management of a RBF system.

PMID- 20807248
TI  - Post-dural puncture headache: Part II--prevention, management, and prognosis.
AB  - Post-dural puncture headache (PDPH) is a frequent complication of lumbar
      puncture, performed for diagnostic or therapeutic purposes or accidentally, as a
      complication of epidural anesthesia. As PDPH can be disabling, clinicians who
      perform these procedures should be familiar with strategies for preventing this
      disorder. Since the best preventative measures sometimes fail, clinicians should
      also be familiar with the therapeutic approaches for PDPH. Herein, we review the
      procedure-related risk factors for PDPH, the prognosis of PDPH and the studies of
      PDPH treatment. We divide the therapeutic approach to PDPH into 4 stages:
      conservative management, aggressive medical management, conventional invasive
      treatments, and the very rarely employed less conventional invasive treatments
      and provide management algorithm to facilitate treatment.

PMID- 20807250
TI  - What is the role of dependence-related behavior in medication-overuse headache?
AB  - Medication-overuse headache (MOH) can be viewed as an interaction between the
      worsening of the primary headache course and individual predispositions for
      dependence. We present here a review of the clinical and biological data raising
      the role of dependence-related behavior in MOH. Indeed, several clinical studies
      show that acute headache medications containing psychoactive components
      (barbiturates, opiates) are associated with an increased risk of MOH. Diagnostic
      and Statistical Manual of Mental Disorders, 4th edition substance dependence
      criteria were identified in a sub-group of MOH patients. Comorbidity between MOH
      and substance-related disorders has also been showed. Recent neuroimaging,
      biological, and pharmacogenetic studies suggest the existence of an overlap
      between the pathophysiological mechanisms of MOH and those of substance-related
      disorders. These data support the proposition of separating 2 sets of MOH
      patients: the first one in which the illness is mainly due to the worsening of
      the headache course, and the second one in which behavioral issues are a major
      determinant of the illness. Detection of a psychological dependence component in
      a sub-group of MOH patients should have direct relevance to disease management.

PMID- 20807249
TI  - Role of 2 common variants of 5HT2A gene in medication overuse headache.
AB  - OBJECTIVE: The aim of the present study was to evaluate a possible involvement of
      2 polymorphisms of the serotonin 5HT2A receptor gene (A-1438G and C516T) as risk
      factors for medication overuse headache (MOH) and whether the presence of these
      polymorphic variants might determine differences within MOH patients in monthly
      drug consumption. BACKGROUND: Despite a growing scientific interest in the
      mechanisms underlying the pathophysiology of MOH, few studies have focused on the
      role of genetics in the development of the disease, as well as on the genetic
      determinants of the inter-individual variability in the number of drug doses
      taken per month. METHODS: Our study was performed by polymerase chain reaction
      (PCR) and PCR-restriction fragment length polymorphism on genomic DNA extracted
      from peripheral blood of 227 MOH patients and 312 control subjects. Genotype
      specific risks were estimated as odds ratios with associated 95% confidence
      intervals by unconditional logistic regression and adjusted for age and gender. A
      stepwise multiple linear regression analysis was employed to identify significant
      predictors of the number of drug doses taken per month. RESULTS: No significant
      association was found between 5HT2A A and 1438G and C516T gene polymorphisms and
      MOH risk. In contrast, a higher consumption of monthly drug doses was observed
      among 516T 5HT2A carriers (median 50, range 13-120) compared to 516CC patients
      (median 30, range 12-128) (Mann-Whitney U-test, P = .018). In the stepwise
      multiple regression analysis, C516T 5HT2A polymorphism (P = .018) and class of
      overused drug (P = .047) emerged as significant, independent predictors of the
      monthly drug consumption in MOH patients. CONCLUSIONS: Although our results do
      not support a major role of the A-1438G and C516T polymorphic variants of the
      5HT2A gene in the susceptibility of MOH, our findings support an influence of the
      C516T polymorphism on the number of symptomatic drug doses taken and, possibly,
      on the drug-seeking behavior in these patients.

PMID- 20807251
TI  - A case of unilateral burning mouth syndrome of neuropathic origin.
AB  - The neuropathic origin of a case of unilateral burning mouth syndrome, previously
      diagnosed as psychogenic, was ascertained by intra-oral mucosa biopsy, which
      showed a severe sensory fibers damage, probably caused by maxillary anesthetic
      block and dental surgery.

PMID- 20807252
TI  - Pregnancy in HIV-infected teenagers in London.
AB  - OBJECTIVE: The aim of the study was to describe pregnancies in HIV-infected
      teenagers. METHODS: A review of the case notes of HIV-infected pregnant teenagers
      aged 13-19 years from 12 London hospitals was carried out for the period 2000
      2007. RESULTS: There were 67 pregnancies in 58 young women, of whom one was known
      to have acquired HIV vertically. The overall mother-to-child transmission (MTCT)
      rate of HIV was 1.5% (one of 66). There were 66 live births. Median ages at HIV
      diagnosis and conception were 17 and 18 years, respectively. Sixty-three per cent
      of women were diagnosed with HIV infection through routine antenatal screening.
      Eighty-two per cent of pregnancies (41 of 50) were unplanned, with 65% of women
      (26 of 40) using no contraception. Forty-three per cent of the women (20 of 46)
      had a past history of a sexually transmitted infection (STI). In 63 pregnancies,
      antiretroviral therapy was started post-conception, with prevention of HIV MTCT
      the only indication in 81% of cases. Fifty-eight per cent of those on highly
      active antiretroviral therapy (HAART) had an undetectable HIV viral load by
      delivery. Eighty-seven per cent were uncomplicated pregnancies. Seventy-one per
      cent delivered by Caesarean section and 21% (14 of 64) had a preterm delivery
      (<37 weeks). In the 12 months after delivery, 45% of women received contraceptive
      advice and 25% of women became pregnant again. CONCLUSION: Obstetric and
      virological outcomes were favourable in this group of HIV-infected young women.
      However, the majority of pregnancies were unplanned with poor documentation of
      contraception use and advice and low rates of STI screening. A quarter of women
      conceived again within 12 months of delivery. Effective measures to reduce STIs,
      unplanned pregnancies and onward HIV transmission in HIV-infected teenagers are
      needed.

PMID- 20807253
TI  - Overcoming obstacles to late presentation for HIV infection in Europe.
AB  - OBJECTIVE: The central goal of the HIV in Europe Initiative is to promote testing
      and treatment throughout Europe and Central Asia in order to decrease the number
      of people living with HIV presenting late for care. This article summarizes the
      results from the HIV in Europe 2009 Conference and the early results of the
      projects set up by the initiative, and discusses their implications for the
      future. METHODS: In November 2009, 100 key stakeholders from 25 countries met in
      Stockholm at the HIV in Europe Conference. The focus was to address five key
      issues that contribute to the barriers to testing identified in 2007 at an
      innovative HIV conference. The conference discussed barriers to testing and other
      reasons for late presentation and outlined concrete recommendations to address
      the problem. RESULTS: An early result of the initiative has been stimulation of
      the process of reaching a consensus definition of what is meant by a 'late
      presenter', with this definition to be implemented at the European level. Steps
      are being taken to advocate for appropriate health policies and surveillance data
      related to HIV throughout Europe. Also, the initiative has set up projects
      related to the barriers to testing, i.e. criminalization law, stigmatization and
      lack of offering of testing for people presenting with certain indicator
      diseases. CONCLUSIONS: The final results of ongoing projects will be published
      and widely disseminated in 2010 and beyond. The HIV in Europe Initiative will
      continue to reinforce collaboration, advocacy and networking activities in the
      field throughout Europe.

PMID- 20807255
TI  - Next-generation small RNA sequencing for microRNAs profiling in the honey bee
      Apis mellifera.
AB  - MicroRNAs (miRNAs) are key regulators in various physiological and pathological
      processes via post-transcriptional regulation of gene expression. The honey bee
      (Apis mellifera) is a key model for highly social species, and its complex social
      behaviour can be interpreted theoretically as changes in gene regulation, in
      which miRNAs are thought to be involved. We used the SOLiD sequencing system to
      identify the repertoire of miRNAs in the honey bee by sequencing a mixed small
      RNA library from different developmental stages. We obtained a total of
      36,796,459 raw sequences; of which 5,491,100 short sequences were fragments of
      mRNA and other noncoding RNAs (ncRNA), and 1,759,346 reads mapped to the known
      miRNAs. We predicted 267 novel honey bee miRNAs representing 380,182 short reads,
      including eight miRNAs of other insects in 14,107,583 genome-mapped sequences. We
      verified 50 of them using stem-loop reverse-transcription PCR (RT-PCR), in which
      35 yielded PCR products. Cross-species analyses showed 81 novel miRNAs with
      homologues in other insects, suggesting that they were authentic miRNAs and have
      similar functions. The results of this study provide a basis for studies of the
      miRNA-modulating networks in development and some intriguing phenomena such as
      caste differentiation in A. mellifera.

PMID- 20807256
TI  - Effect of cationic charge and hydrophobic index of cellulose-based polymers on
      the semipermanent dyestuff process for hair.
AB  - In this work, the effects of a new class of polymers generally used in hair and
      skin cleansing products, the SoftCAT (SofCAT SL and SoftCAT SX), on the dye
      uptake on the hair fibre and the fading effects has been studied. These polymers,
      based on quaternary ammonium salts of hydroxyethylcellulose, are cationic
      products that differ in viscosity, hydrophobic substitution index (HS) and/or
      cationic substitution (CS, % N). UV-Vis spectroscopy has been used to analyse the
      extracted dyes from the hair cuticle and the cortex. The results indicate that
      the presence of polymers in the dye bath improve both the quality of the dyeing
      process and the anti-fading effect during the washing cycles. This phenomenon is
      postulated to be attributable to the polymers hydrophobically bonding with the
      dyes and so facilitating their increased penetration into the hair.

PMID- 20807257
TI  - Infant skin physiology and development during the first years of life: a review
      of recent findings based on in vivo studies.
AB  - Infant skin is often presented as the cosmetic ideal for adults. However,
      compared to adult skin it seems to be more prone to develop certain pathological
      conditions, such as atopic dermatitis and irritant contact dermatitis. Therefore,
      understanding the physiology of healthy infant skin as a point of reference is of
      interest both from the cosmetic as well as from the clinical point of view.
      Clinical research on healthy infants is, however, limited because of ethical
      considerations of using invasive methods and therefore until recently data has
      been scarce. Technical innovations and the availability of non-invasive in vivo
      techniques, such as evaporimetry, electrical impedance measurement, in vivo video
      and confocal microscopy, and in vivo fibre-optic based spectroscopy, opened up
      the field of in vivo infant skin physiology research. Studies incorporating such
      methods have demonstrated that compared to adult, infant skin continues to
      develop during the first years of life. Specifically, infant skin appears to have
      thinner epidermis and stratum corneum (SC) as well as smaller corneocytes at
      least until the second year of life. The water-handling properties are not fully
      developed before the end of the first year and infant SC contains more water and
      less amounts of natural moisturizing factors. Such findings re-evaluate the old
      notions that skin is fully matured at birth. Armed with this knowledge, we are in
      a position not only to better understand infant dermatological conditions but
      also to design better skin care products respecting the distinct qualities of
      infant skin.

PMID- 20807259
TI  - A rapid High Performance Liquid Chromatographic (HPLC) method for the
      simultaneous determination of seven UV filters found in sunscreen and cosmetics.
AB  - A rapid High Performance Liquid Chromatographic (HPLC) method was developed for
      the simultaneous determination of seven Ultra Violet (UV) filters most commonly
      found in cosmetics and sunscreen. The object of the method development was to
      provide a reliable rapid method, that would simultaneously separate a combination
      of the UV Filters, most commonly found in cosmetics and sunscreen products,
      utilizing a minimum of environmentally friendly solvents. The compounds separated
      were: benzophenone 3 (BZ3), methylbenzildene camphor (MBC), octyl dimethyl PABA
      (ODP), octocrylene (OCR), octyl methoxycinnamate (OMC), butyl -
      methoxydibenzoylmethane (BDM) and octyl salicylate (OS). An adjusted mobile phase
      consisting of ethanol and 1% acetic acid, combined with a Thermo Hypersil C(18)
      BDS 3 micron column resulted in a method, which allowed the analysis of the seven
      compounds in seven minutes. The proposed method was validated utilising the
      International Congress on Harmonisation (ICH) and the Food and Drug
      Administration (FDA) guidelines. All parameters examined were found to be well
      within the stated guidelines.

PMID- 20807258
TI  - Expert opinion and review article: The timing of comedone extraction in the
      treatment of premenstrual acne--a proposed therapeutic approach.
AB  - The face is the most exposed part of our body, and deterioration of facial
      appearance, through disease or ageing, causes psychological distress. Acne
      lesions and subsequent pigmentation changes contribute to the unevenness of skin
      colour that is detrimental to facial attractiveness and leads to rejection and
      stigmatization in our society. The purpose of this review is to look at the root
      causes of premenstrual acne and, for the first time ever, propose that the
      specific timing of treatment can, at least in part, resolve the acne lesions. We
      postulate that it is the timing of the manual extraction that matters in
      resolving premenstrual acne and that the effectiveness of this therapy could be
      improved. Based on the reviewed evidence, we propose that it is important to
      remove the comedones at the time of ovulation, prior to the reduction of the size
      of the sebaceous orifice and epidermal barrier function, to counteract the onset
      of increased sebum production, prevent blockage of the pores and subsequent
      bacterial colonization and inflammation. If performed successfully, the
      extraction may contribute to a reduction in inflamed acne lesions and thus
      benefit women by increasing their facial attractiveness, well-being, social
      function and thereby decrease psychological stress.

PMID- 20807260
TI  - Evaluation of the efficacy of a dill extract in vitro and in vivo.
AB  - Lysyl oxidase-like (LOXL) is an extracellular enzyme that catalyses the cross
      linking between microfibrils and tropoelastin (TE), thereby ensuring elastic
      fibre functionality. With ageing, LOXL expression decreases, thus participating
      in the loss of skin elasticity. In a previous study, we showed that a dill seed
      extract [INCI name: Peucedanum graveolens (Dill) extract] could increase LOXL
      expression in cultured dermal fibroblasts. Besides, we showed a good correlation
      between the measurements of skin elasticity obtained in vitro and in vivo using a
      fully automated bio-tribometer designed to measure the biomechanical properties
      of soft and complex materials like skin. The aim of this study was to evaluate
      the ability of the dill extract to improve skin elasticity in vitro and in vivo
      using different models. Using the bio-tribometer, we first showed that the
      lateral elasticity of dermis equivalents (DEs) treated with the dill extract at
      1% was significantly increased by +29% (P < 0.01) when compared to untreated DEs.
      In vivo, skin firmness and elastic recovery measured using cutometry methods were
      also significantly improved compared to placebo in volunteers treated for 56 days
      with a formula containing 1% of dill extract. Moreover, the clinical evaluation
      evidenced significant improvements in 'skin elasticity' compared to placebo. A
      majority of subjects treated with the dill extract also noted significant
      improvements in skin elasticity, firmness and slackness of the jaw line. Finally,
      mean wrinkle area and length were also significantly reduced compared to placebo
      after 84 days as measured using silicone replicas taken from the crow's feet. In
      summary, this study showed that the dill extract could improve elasticity of DEs
      in vitro as well as skin biomechanical properties and appearance in vivo. It also
      highlights the relevance of using the bio-tribometer as an exploratory tool for
      the measurement of skin elasticity in vitro.

PMID- 20807254
TI  - Recruitment of HIV/AIDS treatment-naive patients to clinical trials in the highly
      active antiretroviral therapy era: influence of gender, sexual orientation and
      race.
AB  - BACKGROUND: In the USA, women, racial/ethnic minorities and persons who acquire
      HIV infection through heterosexual intercourse represent an increasing proportion
      of HIV-infected persons, and yet are frequently underrepresented in clinical
      trials. We assessed the demographic predictors of trial participation in
      antiretroviral-naive patients. METHODS: Patients were characterized as trial
      participants if highly active antiretroviral therapy (HAART) was initiated within
      a clinical trial. Prevalence ratios (PRs) were obtained using binomial
      regression. RESULTS: Between 1996 and 2006, 30% of 738 treatment-naive patients
      initiated HAART in a clinical trial. Trial participation rates for men who have
      sex with men (MSM), heterosexual men, and women were respectively 36.5, 29.6 and
      24.3%. After adjustment for other factors, heterosexual men appeared less likely
      to participate in trials compared with MSM [PR 0.79, 95% confidence interval (CI)
      0.57, 1.11], while women were as likely to participate as MSM (PR 0.97, 95% CI
      0.68, 1.39). The participation rate in Black patients (25.9%) was lower compared
      with non-Black patients (37.5%) (adjusted PR 0.80, 95% CI 0.60, 1.06).
      CONCLUSIONS: In our clinical setting, gender did not appear to impact
      participation in HIV treatment trials, but Black patients were slightly less
      likely to participate in these trials. Considering the substantial proportion of
      HIV-infected patients who are Black, future trials need to consider strategies to
      incorporate such underrepresented populations.

PMID- 20807261
TI  - Differences in visual perception of age and attractiveness of female facial and
      body skin.
AB  - Perception of age and health is critical in the judgement of attractiveness. The
      few studies conducted on the significance of apparent skin condition on human
      physical appearance have studied faces alone or isolated fields of images facial
      skin. Little is known about whether perception of the face matches that of other
      body parts or if body skin affects overall age and attractiveness perception when
      presented in combination with facial skin. We hypothesized that independent
      presentation of female faces, chests and arms (including hands) - cropped from a
      full face and upper body image - would result in significant differences in
      perception of age and attractiveness compared to the corresponding composite.
      Furthermore, we sought to investigate whether relatively young and attractive
      looking skin on selected, individual parts of the body affects overall
      perception. Digital photographs of 52 women aged 45-65 years were collected and
      processed to yield four derivative sets of images: One set showed the composite
      of all features, i.e. the face, the chest and the arms, whereas the other three
      were cropped carefully to show each part of the upper body described above
      independently. A total of 240 participants judged these faces for perceived age
      and attractiveness. Our results showed significant differences in perception with
      the chest and the arms being judged significantly younger than the face or
      composite image of the same women. Moreover, arms and chest images were perceived
      as more attractive than face and composite images. Finally, regression analysis
      indicated that differences between the perceived and chronological values of
      overall age perception could be predicted by age perception of the face and arms.
      These results continue to support the significance of facial age perception in
      assessment of a woman's age, but highlight that body skin also plays a role in
      overall age impression.

PMID- 20807263
TI  - On the effects of a plant extract of Orthosiphon stamineus on sebum-related skin
      imperfections.
AB  - Overproduction of sebum is very common and results in an undesirable oily, shiny
      complexion with enlarged pores. Sebum secretion is basically under the control of
      5-alpha reductase, and more particularly under that of type 1 isozyme. But it is
      also highly sensitive to environmental factors such as temperature, humidity and
      food. Moreover, in Asia, the edicts of a flawless facial skin turn oily skin into
      a major concern for Asian women. We identified Orthosiphon stamineus leaf extract
      as an interesting ingredient for reducing the oily appearance of skin thanks to
      its ability to reduce 5-alpha reductase type 1 expression in normal human
      epidermal keratinocytes in vitro. This was confirmed ex vivo, where Orthosiphon
      stamineus leaf extract was shown to reduce 5-alpha reductase activity as well as
      the production of squalene, one of the main components of sebum that was used as
      a tracer of sebum. To evaluate the efficacy of Orthosiphon stamineus leaf extract
      at reducing sebum-related skin imperfections in vivo, we performed two different
      clinical studies, one in France on a panel of Caucasian volunteers and the other
      one in Thailand on a panel of Asian volunteers. Using instrumental techniques as
      well as clinical evaluation and self-evaluation, we could highlight that an O/W
      cosmetic formula containing 2% of Orthosiphon stamineus leaf extract could
      visibly reduce the oily appearance of skin as well as the size of pores, thus
      leading to a significant improvement of complexion evenness and radiance.
      Overall, the results obtained were better than those observed with the same
      formula containing 1% of zinc gluconate, an ingredient frequently used in oily
      skin care products.

PMID- 20807262
TI  - In vitro and in vivo efficacy of sulfo-carrabiose, a sugar-based cosmetic
      ingredient with anti-cellulite properties.
AB  - Most of adult women exhibit cellulite on the hips, buttock and thighs. Although
      extracellular matrix and lymphatic system disorders can increase its appearance,
      cellulite basically results from an excessive fat storage in the adipose tissue
      which exerts considerable pressure on the surrounding skin tissue and creates a
      dimpled irregular appearance. Caffeine, the most widely used anti-cellulite
      ingredient, favours fat break-down by inhibiting the phosphodiesterase enzyme and
      encouraging a high intracellular level of cAMP. A series of studies has shown
      that spermine and spermidine, two ubiquitous polyamines, encouraged fat storage
      and slowed fat break-down in the adipose tissue. Besides, it was shown that
      heparan sulfate glycosaminoglycans had a strong affinity for polyamines. To
      design a new cosmetic ingredient with anti-cellulite properties, we used
      molecular modelling to screen several ingredients with a structure similar to
      that of heparan sulfate glycosaminoglycans. This way, we identified sulfo
      carrabiose as a potent molecule for trapping spermine and spermidine. These
      virtual results were first confirmed in tubo where sulfo-carrabiose was shown to
      dose-dependently inactivate spermine and spermidine. In vitro, adipocytes
      cultured with sulfo-carrabiose exhibited a significant reduction of lipogenesis
      and a significant increase of lipolysis. When sulfo-carrabiose was incorporated
      in a cosmetic formula, significant improvements were observed in thigh
      circumference, with better results than those obtained with caffeine after 28
      days of use. Furthermore, a combination of caffeine and sulfo-carrabiose led to
      results significantly better than those obtained with caffeine alone. As measured
      by fringe projection, thigh volume was also significantly reduced after sulfo
      carrabiose treatment. Finally, the appearance of cellulite assessed by clinical
      evaluation was also significantly reduced within 28 days.

PMID- 20807264
TI  - Interleukin-10 microsatellite variants and the risk of acute coronary syndrome
      among Tunisians.
AB  - The objective of the study was to investigate the association of interleukin (IL)
      10 promoter microsatellite polymorphisms, linked with altered IL-10 secretion,
      with the susceptibility to acute coronary syndrome (ACS) in adult Tunisian
      patients. We genotyped 291 ACS patients and 291 age-, gender- and ethnically
      matched control subjects for the microsatellites IL-10R [X78437.2g.5325CA(11_15)]
      and IL-10G [X78437.2g.8134CA(14_29)] by PCR-based assays. Haplotypes were
      reconstructed using maximum likelihood method. Regression analysis was used in
      determining the risk imparted by specific IL-10 genotypes and haplotypes. A
      significant decrease in IL-10G12 (24 CA repeats) (P<0.001; OR=0.465) and IL-10G15
      (27 CA repeats) (P=0.043; OR=0.232), and a significant increase in the low IL-10
      producer allele, IL-10R3 (14 CA repeats) (P=0.049; OR=1.461), microsatellites
      were seen in the ACS group compared with controls. Of the possible 14 haplotypes
      constructed, there was an enrichment of the R2G9 (13CA vs. 21CA) haplotype in
      controls [P=0.019; adjusted OR (95% CI)=0.67 (0.48-0.94)] and R2G15 (13CA vs.
      27CA) haplotype in cases [P=0.042; adjusted OR (95% CI)=5.29 (1.06-26.30)], thus
      assigning a protective and susceptible nature to these haplotypes respectively.
      The differential association of IL-10 microsatellite alleles and haplotypes with
      ACS suggests that IL-10 contributes to ACS pathogenesis. While the functional
      attributes of these microsatellite markers remain to be seen, it is likely that
      they have distinct functional properties (altered IL-10 secretion), which in turn
      affect the susceptibility to ACS development.

PMID- 20807265
TI  - Alternative antiandrogen therapy in patients with castration-resistant prostate
      cancer: a single-center experience.
AB  - Outcomes of alternative (second-line) antiandrogen therapy in 112 patients with
      relapsing prostate cancer after first-line hormonal therapy were analyzed. A good
      response (prostate-specific antigen [PSA] decrease 50%) and a partial response
      (PSA decrease of 0-50%) by switching from bicalutamide (BCL) to flutamide (FLT)
      and from FLT to BCL were achieved in 35.4% (28/79) and 30.4% (24/79), and in
      45.0% (9/20) and 20.0% (4/20) of cases, respectively. A good response and a
      partial response with the change from chlormadinone acetate (CMA) to a non
      steroidal antiandrogen (FLT or BCL)and from a non-steroidal antiandrogen to CMA
      were obtained in 25.0% (2/8) and 37.5% (3/8), and in 20.0% (1/5) and 0% (0/5)of
      cases, respectively. In multivariate analyses, a second-line good response was
      significantly predictive of cause-specific survival from first therapy relapse to
      cancer death in all patients. Patients (52/112, 46.4%) with 30% decrease in PSA
      levels were associated with significantly better cause-specific survival as
      measured from the start of first-line treatment and first-line relapse.

PMID- 20807266
TI  - Real-time Virtual Sonography for navigation during targeted prostate biopsy using
      magnetic resonance imaging data.
AB  - OBJECTIVES: To evaluate the effectiveness of the medical navigation technique,
      namely, Real-time Virtual Sonography (RVS), for targeted prostate biopsy.
      METHODS: Eighty-five patients with suspected prostate cancer lesions using
      magnetic resonance imaging (MRI) were included in this study. All selected
      patients had at least one negative result on the previous transrectal biopsies.
      The acquired MRI volume data were loaded onto a personal computer installed with
      RVS software, which registers the volumes between MRI and real-time ultrasound
      data for real-time display. The registered MRI images were displayed adjacent to
      the ultrasonographic sagittal image on the same computer monitor. The suspected
      lesions on T2-weighted images were marked with a red circle. At first suspected
      lesions were biopsied transperineally under real-time navigation with RVS and
      then followed by the conventional transrectal and transperineal biopsy under
      spinal anesthesia. RESULTS: The median age of the patients was 69 years (56-84
      years), and the prostate-specific antigen level and prostate volume were 9.9
      ng/mL (4.0-34.2) and 37.2 mL (18-141), respectively. Prostate cancer was detected
      in 52 patients (61%). The biopsy specimens obtained using RVS revealed 45/52
      patients (87%) positive for prostate cancer. A total of 192 biopsy cores were
      obtained using RVS. Sixty-two of these (32%) were positive for prostate cancer,
      whereas conventional random biopsy revealed cancer only in 75/833 (9%) cores (P <
      0.01). CONCLUSIONS: Targeted prostate biopsy with RVS is very effective to
      diagnose lesions detected with MRI. This technique only requires additional
      computer and RVS software and thus is cost-effective. Therefore, RVS-guided
      prostate biopsy has great potential for better management of prostate cancer
      patients.

PMID- 20807267
TI  - Fetal and infant growth patterns of the mandibular symphysis in modern humans and
      chimpanzees (Pan troglodytes).
AB  - Comparison of the early development of the mandibular symphysis between primates
      and modern humans is of particular interest in human palaeontology. Using
      geometric morphometric methods, we explored and compared the ontogenetic shape
      changes of 14 chimpanzee mandibles (Pan troglodytes) against 66 human CT-scanned
      mandibles over the age range from fetal life to the complete emergence of the
      deciduous dentition in a visualization incorporating the deciduous tooth
      arrangement. The results reveal that the symphysis is anteriorly inclined in the
      youngest chimpanzee fetuses but develops an increasingly vertical orientation up
      until birth. At the same time, the anterior teeth reorient before a vertical
      emergence, and a symphyseal tuber appears on the labial side. When the deciduous
      canine emerges, the symphysis inclines anteriorly again, exhibiting the adult
      characteristic slope. These two phases are characterized by a repositioning of
      the simian shelf. Unlike chimpanzees, the human symphysis remains vertical
      throughout fetal development. However, the combination of morphological changes
      observed in chimpanzee fetuses is similar to that of modern humans after birth,
      as the mental region projects forward. By elongating the alveolar process, the
      inclination of the chimpanzee symphysis could be a key event for emergence of the
      deciduous canine, as space is lacking at the alveolar ridge in a vertical
      symphysis once the deciduous incisors and molars have emerged. The repositioning
      of the simian shelf suggests that the suprahyoid muscles have a significant
      influence on the anterior growth of the symphysis. The anteroposterior
      positioning of the basal symphysis in both species may be related to hyoid bone
      position during ontogeny.

PMID- 20807268
TI  - Quantitative morphometry of the orbit in Chinese adults based on a three
      dimensional reconstruction method.
AB  - The three-dimensional (3D) reconstruction technique serves as a practical tool in
      diagnosis, surgical planning, and outcome prediction of plastic and
      reconstructive surgery. In our study, the morphologic features of the Chinese
      adult orbit were described by 11 anatomic parameters using a 3D reconstruction
      technique. Sixty-four Chinese adults were selected randomly from patients who had
      undergone craniofacial computed tomography (CT) scans to diagnose conditions
      other than craniofacial or orbital deformations. The morphologic parameters of
      orbit such as bony orbital volume, orbital foramen area and orbital rim perimeter
      were measured on 3D models using this technique. Differences between the two
      orbits and between the two sexes were investigated. The method of measurement
      showed high reproducibility of results. No difference between the two orbits was
      found. There were significant differences between men and women in all anatomic
      parameters other than orbital height. In men and women, respectively, mean bony
      orbital volume was 26.02 and 23.32 mL, mean orbital foramen area 11.80 and 11.10
      cm2, mean orbital rim perimeter 12.65 and 12.20 cm, mean orbital height 33.35 and
      33.22 mm, mean orbital width 40.02 and 38.00 mm; mean orbital floor length 47.93
      and 46.18 mm, mean orbital roof length 52.93 and 50.89 mm, mean medial orbital
      wall length 46.43 and 44.41 mm, mean lateral orbital wall length 48.38 and 46.91
      mm, mean intraorbital distance 27.18 and 25.11 mm, mean extra-orbital distance
      98.77 and 93.69 mm. It is concluded that the measurements of these orbital
      parameters could be obtained from a 3D reconstruction method. The two orbits were
      symmetric based on orbital volume and other anatomic parameters. Orbital size was
      significantly smaller in women than in men; orbital height, however, was similar.
      The findings of the present study allow for quantification of the orbital
      features of Chinese adults and provide parameters for preoperative planning and
      prediction of postoperative outcome.

PMID- 20807269
TI  - Stereological assessment of pancreatic beta-cell mass development in male Zucker
      Diabetic Fatty (ZDF) rats: correlation with pancreatic beta-cell function.
AB  - The present study was initiated to improve our understanding of pancreatic beta
      cell dynamics in male Zucker Diabetic Fatty (ZDF) rats and hence provide a
      framework for future diabetes studies in this animal model. Male ZDF rats from 6,
      8, 10, 12, 14, 16, 20 and 26 weeks of age were subjected to an oral glucose
      tolerance test (OGTT). The animals were then euthanized and pancreases were
      removed for morphometric analyses of pancreatic beta-cell mass. As evident by a
      marked fourfold increase in insulin secretion, insulin resistance developed
      rapidly from 6 to 8 weeks of age. Simultaneously, the pancreatic beta-cell mass
      expanded from 6.17 +/- 0.41 mg at 6 weeks of age, reaching a maximum of 16.5 +/-
      2.5 mg at 16 weeks of age, at which time pancreatic beta-cell mass gradually
      declined. The corresponding changes in glucose/insulin homeostasis were analysed
      using a standard insulin sensitivity index (ISI), an area under the curve (AUC)
      glucose-insulin index, or simple semi-fasted glucose levels. The study
      demonstrated that male ZDF rats underwent rapid changes in pancreatic beta-cell
      mass from the onset of insulin resistance to frank diabetes coupled directly to
      marked alterations in glucose/insulin homeostasis. The study underscores the need
      for a critical co-examination of glucose homeostatic parameters in studies
      investigating the effects of novel anti-diabetic compounds on pancreatic beta
      cell mass in the male ZDF rat. A simple assessment of fasting glucose levels
      coupled with information about age can provide a correct indication of the actual
      pancreatic beta-cell mass and the physiological state of the animal.

PMID- 20807270
TI  - Comparative anatomy, homologies and evolution of the pectoral and forelimb
      musculature of tetrapods with special attention to extant limbed amphibians and
      reptiles.
AB  - The main aim of the present work is to synthesize the information obtained from
      our dissections of the pectoral and forelimb muscles of representative members of
      the major extant taxa of limbed amphibians and reptiles and from our review of
      the literature, in order to provide an account of the comparative anatomy,
      homologies and evolution of these muscles in the Tetrapoda. The pectoral and
      forelimb musculature of all these major taxa conform to a general pattern that
      seems to have been acquired very early in the evolutionary history of tetrapods.
      Although some muscles are missing in certain taxa, and a clear departure from
      this general pattern is obviously present in derived groups such as birds, the
      same overall configuration is easily distinguishable in these taxa. Among the
      most notable anatomical differences between the groups, one that seems to have
      relevant evolutionary and functional implications, concerns the distal insertion
      points of the forearm musculature. In tetrapods, the muscles of the radial and
      ulnar complexes of the forearm are pleisomorphically mainly inserted onto the
      radius/ulna or onto the more proximal carpal bones, but in mammals some of these
      muscles insert more distally onto bones such as the metacarpals. Interestingly, a
      similar trend towards a more distal insertion of these muscles is also found in
      some non-mammalian tetrapod taxa, such as some anurans (e.g. Phyllomedusa). This
      may be correlated with the acquisition of more subtle digital movement abilities
      in these latter taxa.

PMID- 20807271
TI  - Atrial fibrosis helps select the appropriate patient and strategy in catheter
      ablation of atrial fibrillation: a DE-MRI guided approach.
AB  - MRI for AF Patient Selection and Ablation Approach. INTRODUCTION: Left atrial
      (LA) fibrosis and ablation related scarring are major predictors of success in
      rhythm control of atrial fibrillation (AF). We used delayed enhancement MRI (DE
      MRI) to stratify AF patients based on pre-ablation fibrosis and also to evaluate
      ablation-induced scarring in order to identify predictors of a successful
      ablation. METHODS AND RESULTS: One hundred and forty-four patients were staged by
      percent of fibrosis quantified with DE-MRI, relative to the LA wall volume:
      minimal or Utah stage 1; <5%, mild or Utah stage 2; 5-20%, moderate or Utah stage
      3; 20-35%, and extensive or Utah stage 4; >35%. All patients underwent pulmonary
      vein (PV) isolation and posterior wall and septal debulking. Overall, LA scarring
      was quantified and PV antra were evaluated for circumferential scarring 3 months
      post ablation. LA scarring post ablation was comparable across the 4 stages. Most
      patients had either no (36.8%) or 1 PV (32.6%) antrum circumferentially scarred.
      Forty-two patients (29%) had recurrent AF over 283 +/- 167 days. No recurrences
      were noted in Utah stage 1. Recurrence was 28% in Utah stage 2, 35% in Utah stage
      3, and 56% in Utah stage 4. Recurrence was predicted by circumferential PV
      scarring in Utah stage 2 and by overall LA wall scarring in Utah stage 3. No
      recurrence predictors were identified in Utah stage 4. CONCLUSIONS:
      Circumferential PV antral scarring predicts ablation success in mild LA fibrosis,
      while posterior wall and septal scarring is needed for moderate fibrosis. This
      may help select the proper candidate and strategy in catheter ablation of AF.

PMID- 20807272
TI  - Isthmus animus?

PMID- 20807273
TI  - Preventing atrial fibrillation: more evidence to turn up the heat.

PMID- 20807274
TI  - Correlative anatomy for the electrophysiologist, part II: cardiac ganglia,
      phrenic nerve, coronary venous system.
AB  - Cardiac Ganglia, Phrenic Nerve, Coronary Venous System. There is an increasing
      need for invasive electrophysiologists to appreciate the exact anatomy of the
      epicardial space and the coronary veins. The location of the epicardial fat, the
      complementary relationship with the main cardiac veins, and the location of
      sensitive structures (arteries, phrenic nerve, esophagus) have become required
      knowledge for electrophysiologists, and accessing the epicardial space with this
      thorough knowledge of the pericardial sinuses and recesses is essential to allow
      radiographic correlation during catheter manipulation. In this review, we briefly
      describe the anatomy of the pericardial space and then discuss the specific
      correlation for the invasive electrophysiologist, highlighting epicardial access,
      catheter navigation, and avoidance of collateral injury, with specific attention
      to the important recesses of the pericardial space, their regional anatomy, and
      radiographic correlation when navigating catheters to these locations. We also
      discuss the anatomy of the main cardiac veins in the context of catheter mapping
      and ablation of the epicardial substrate through the venous system and without
      subxiphoid pericardial access. In part II of this series we discuss the detailed
      regional anatomy of the cardiac ganglia, phrenic nerve, and coronary venous
      system.

PMID- 20807275
TI  - Perhaps past performance does predict future results after all: a key to
      evaluating treatment interventions in vasovagal syncope.

PMID- 20807276
TI  - Regular narrow QRS tachycardia with apparent atrioventricular dissociation: what
      is the mechanism?

PMID- 20807277
TI  - The slow pace of the heart and the objectives of molecular cardiology.

PMID- 20807278
TI  - Efficacy of acupuncture in preventing atrial fibrillation recurrences after
      electrical cardioversion.
AB  - INTRODUCTION: In traditional Chinese medicine, stimulation of the Neiguan spot
      has been utilized to treat palpitations. We evaluated whether acupuncture might
      prevent or reduce the rate of arrhythmia recurrences in patients with persistent
      atrial fibrillation (AF). METHODS AND RESULTS: We studied 80 patients with
      persistent AF after restoring sinus rhythm with electrical cardioversion. Twenty
      six subjects who were already on amiodarone treatment constituted the AMIO
      reference group. The remaining patients were randomly allocated to receive
      acupuncture (ACU group, n = 17), sham acupuncture (ACU-sham group, n = 13), or
      neither acupuncture nor antiarrhythmic therapy (CONTROL group, n = 24). Patients
      in the ACU and ACU-sham groups attended 10 acupuncture sessions on a once-a-week
      basis. Only in the former group the Neiguan, Shenmen, and Xinshu spots were
      punctured. During a 12-month follow-up, AF recurred in 35 patients. Cumulative AF
      recurrence rates in the AMIO, ACU, ACU-sham, and CONTROL patients were 27%, 35%,
      69%, and 54%, respectively (P = 0.0075, log-rank test). Ejection fraction (P =
      0.0005), hypertension (0.0293), and left atrial diameter (P = 0.0361) were also
      significantly associated with AF recurrence. Compared with AMIO group, recurrence
      rate was similar in ACU patients (hazard ratio: 1.15, 95% CI: 0.38-3.49; P =
      0.801) but significantly higher in ACU-sham and CONTROL patients (3.77, 1.39-10;
      P = 0.009 and 3.15, 1.23-8.06; P = 0.017, respectively) after adjustment for
      ejection fraction, hypertension, and left atrial diameter using Cox modeling.
      CONCLUSION: Our data indicate that acupuncture treatment prevents arrhythmic
      recurrences after cardioversion in patients with persistent AF. This minimally
      invasive procedure was safe and well tolerated.

PMID- 20807280
TI  - Substrate characterization and catheter ablation for monomorphic ventricular
      tachycardia in patients with apical hypertrophic cardiomyopathy.
AB  - VT Ablation in Apical Hypertrophic Cardiomyopathy.  INTRODUCTION: Monomorphic
      ventricular tachycardia (VT) is uncommon in apical hypertrophic cardiomyopathy
      (HCM). The purpose of this study was to define the substrate and role of catheter
      ablation for VT in apical HCM. METHODS: Four patients with apical HCM and
      frequent, drug refractory VT (mean age of 46 +/- 10 years, left ventricular [LV]
      ejection fraction; 54 +/- 14%) underwent catheter ablation with the use of
      electroanatomic mapping. Endocardial mapping was performed in 4 patients and 3
      patients underwent epicardial mapping. RESULTS: In 3 patients, VT was related to
      areas of scar in the apical LV where maximal apical wall thickness ranged from
      14.5 to 17.8 mm, and 2 patients had apical aneurysms. Endocardial and epicardial
      substrate mapping revealed low voltage (<1.5 mV) scar in both endocardial and
      epicardial LV in 2 and only in the epicardium in 1 patient. Inducible VT was
      abolished with a combination of endocardial and epicardial ablation in 2
      patients, but was ineffective in the third patient who had intramural reentry
      that required transcoronary ethanol ablation of an obtuse marginal vessel for
      abolition. The fourth patient had focal nonsustained repetitive VT from right
      ventricular outflow tract (RVOT), consistent with idiopathic RVOT-VT, that was
      successfully ablated. During follow-ups of 3-9 months, all patients remained free
      from VT. CONCLUSION: Monomorphic VT in apical HCM can be due to endocardial,
      epicardial or intramural reentry in areas of apical scar. Epicardial ablation or
      transcoronary alcohol ablation is required in some cases.

PMID- 20807279
TI  - Prevention of ventricular arrhythmia and calcium dysregulation in a
      catecholaminergic polymorphic ventricular tachycardia mouse model carrying
      calsequestrin-2 mutation.
AB  - BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a
      familial arrhythmic syndrome caused by mutations in genes encoding the calcium
      regulation proteins cardiac ryanodine receptor (RyR2) or calsequestrin-2 (CASQ2).
      Mechanistic studies indicate that CPVT is mediated by diastolic Ca(2+) overload
      and increased Ca(2+) leak through the RyR2 channel, implying that treatment
      targeting these defects might be efficacious in CPVT. METHOD AND RESULTS: CPVT
      mouse models that lack CASQ2 were treated with Ca(2+) -channel inhibitors, beta
      adrenergic inhibitors, or Mg(2+) . Treatment effects on ventricular arrhythmia,
      sarcoplasmic reticulum (SR) protein expression and Ca(2+) transients of isolated
      myocytes were assessed. Each study agent reduced the frequency of stress-induced
      ventricular arrhythmia in mutant mice. The Ca(2+) channel blocker verapamil was
      most efficacious and completely prevented arrhythmia in 85% of mice. Verapamil
      significantly increased the SR Ca(2+) content in mutant myocytes, diminished
      diastolic Ca(2+) overload, increased systolic Ca(2+) amplitude, and prevented
      Ca(2+) oscillations in stressed mutant myocytes. CONCLUSIONS: Ca(2+) channel
      inhibition by verapamil rectified abnormal calcium handling in CPVT myocytes and
      prevented ventricular arrhythmias. Verapamil-induced partial normalization of SR
      Ca(2+) content in mutant myocytes implicates CASQ2 as modulator of RyR2 activity,
      rather than or in addition to, Ca(2+) buffer protein. Agents such as verapamil
      that attenuate cardiomyocyte calcium overload are appropriate for assessing
      clinical efficacy in human CPVT.

PMID- 20807281
TI  - Characterization of atrial activation (A-A) intervals during atrial fibrillation
      due to a single driver: do they reflect atrial effective refractory periods?
AB  - BACKGROUND: The mean, median, and minimum local atrial activation (A-A) intervals
      have been used to determine the local atrial effective refractory period (AERP)
      during atrial fibrillation (AF), the underlying assumption being that AF is due
      to multiple reentrant wavelets. OBJECTIVE: We tested the hypothesis that when AF
      is due to a single, rapid, stable reentrant circuit (driver), the minimum and
      mean local A-A intervals will be similar at sites in the reentrant circuit, but
      will vary widely at sites with fibrillatory conduction, making these latter
      intervals unreliable indicators of AERP. METHODS: During sustained AF due to a
      left atrial (LA) driver in 6 sterile pericarditis dogs, electrograms were
      recorded from 186 bipolar electrodes from both atria. A-A intervals were measured
      from each recording site during 1.2 seconds of AF. Minimum A-A intervals as well
      as temporal (within site) and spatial (between sites) variability were determined
      from all sites. RESULTS: A-A intervals from each site during AF demonstrated that
      (1) 90-100% of right atrial (RA) sites and 18-39% of LA sites showed considerable
      (SD > 6 ms) temporal variability; (2) RA and LA sites with fibrillatory
      conduction (SD > 6 ms) showed considerable (a) spatial variability (RA: 9-36 ms;
      LA: 5-27 ms) and (b) variability of the minimum A-A intervals (RA: 14-35 ms; LA
      11-28 ms). CONCLUSION: During AF due to a driver, areas with fibrillatory
      conduction manifested considerable variability in the mean and the minimum A-A
      intervals. Therefore, it is unlikely that any of the A-A intervals reflect AERP.

PMID- 20807282
TI  - Epicardial connections between the pulmonary veins and left atrium: relevance for
      atrial fibrillation ablation.
AB  - INTRODUCTION: Some observations support the existence of epicardial connections
      (ECs) between ipsilateral pulmonary veins (vein to vein ECs [VVECs]), and we have
      observed venoatrial ECs inserted at distance from the pulmonary vein ostium (vein
      to atrium ECs [VAECs]). Our aim was to determine the prevalence of ECs and their
      relevance for pulmonary vein isolation. METHODS AND RESULTS: We studied 100
      consecutive patients with drug-refractory atrial fibrillation who underwent
      ostial pulmonary vein isolation by cooled radiofrequency catheter ablation. A
      VVEC was identified if pulmonary vein pacing activated the ipsilateral vein
      before the atrium, requiring ablation of both venous ostia to isolate either
      pulmonary vein. A VAEC was identified if pacing produced atrial breakthrough
      located at distance from the venous ostium, requiring extraostial ablation to
      isolate the pulmonary vein. Patients with ECs (20%) were younger (P = 0.02) and
      had a higher prevalence of structural heart disease (P = 0.01) than patients
      without ECs. VVECs and VAECs were identified in 32 pulmonary veins (10%) and
      VAECs in 10 veins (3%). Veins with ECs had a higher rate of early recurrence of
      conduction following isolation (29% vs 11%; P = 0.01). CONCLUSION: Twenty percent
      of patients with atrial fibrillation had ECs resistant to ostial ablation in one
      or more pulmonary veins. Isolating veins with ECs may require a different
      ablation approach. These connections are associated with an increased rate of
      early recurrence of conduction. (J Cardiovasc Electrophysiol, Vol. 22, pp. 149
      159, February 2011).

PMID- 20807284
TI  - Regenerative medicine: the promises and perils of a Promethean task: Progress in
      regenerative medicine review series.

PMID- 20807287
TI  - Defining and identifying common elements of and contextual influences on the
      roles of support workers in health and social care: a thematic analysis of the
      literature.
AB  - RATIONALE, AIMS AND OBJECTIVES: Support workers are the largest single group of
      staff involved in the delivery of health and social care in the UK; however,
      their roles are heterogeneous and are influenced by several contextual factors.
      The aim of this study was to elucidate the contribution of the elements and
      context of work undertaken by support workers in health and social care. METHODS:
      Thematic review of the literature 2005/2006, updated in 2008. RESULTS: A total of
      134 papers were included in the review, from which we identified four domains of
      work and four core roles of support workers. The four domains of support worker
      work are direct care, indirect care, administration and facilitation. The four
      'core' attributes of support worker roles were being a helper/enabler, a
      companion, a facilitator and a monitor. The more 'technical' components of
      support worker roles are then shaped by contextual factors such as staffing
      levels and the delegation processes. CONCLUSION: Despite the heterogeneity of
      support worker roles, there are some uniting 'generic' features, which may form
      some or all of the role of these practitioners. Contextual factors influence the
      specific technical aspects of the support role, accounting in part for their
      heterogeneous role.

PMID- 20807285
TI  - Hsp72 mediates TAp73alpha anti-apoptotic effects in small cell lung carcinoma
      cells.
AB  - The transcription factor p73, a member of the p53 family of proteins, is involved
      in the regulation of cell cycle progression and apoptosis. Due to alternative
      promoters and carboxy-terminal splicing, the P73 gene gives rise to a range of
      different isoforms. Interestingly, a particular increase in expression of the
      TAp73alpha isoform has been reported in various tumours. In addition, TAp73alpha
      has been shown to inhibit Bax activation and mitochondrial dysfunctions and
      thereby to confer small cell lung carcinoma (SCLC) cells resistance to drug
      induced apoptosis. However, the precise mechanism by which TAp73alpha exerts its
      pro-survival effect is yet unclear. Here we report that TAp73alpha, but not
      TAp73beta, regulates the expression of inducible Hsp72/HSPA1A. Hsp72 proved to be
      required for the survival effects of TAp73alpha as antisense knockdown of Hsp72
      resulted in an abolishment of the anti-apoptotic effect of TAp73alpha in SCLC
      cells upon Etoposide treatment. Importantly, depletion of Hsp72 allowed
      activation of Bax, loss of mitochondrial membrane potential and lysosomal
      membrane permeabilization in SCLC cells even in the presence of TAp73alpha.
      Finally, we revealed that TAp73beta counteracts the anti-apoptotic effect of
      TAp73alpha by preventing Hsp72 induction. Our results thus provide additional
      evidence for the potential oncogenic role of TAp73alpha, and extend the
      understanding of the mechanism for its anti-apoptotic effect.

PMID- 20807286
TI  - Butyrylcholinesterase interactions with amylin may protect pancreatic cells in
      metabolic syndrome.
AB  - The metabolic syndrome (MetS) is a risk factor for type 2 diabetes mellitus
      (T2DM). However, the mechanisms underlying the transition from MetS to T2DM are
      unknown. Our goal was to study the potential contribution of
      butyrylcholinesterase (BChE) to this process. We first determined the hydrolytic
      activity of BChE in serum from MetS, T2DM and healthy individuals. The 'Kalow'
      variant of BChE (BChE-K), which has been proposed to be a risk factor for T2DM,
      was genotyped in the last two groups. Our results show that in MetS patients
      serum BChE activity is elevated compared to T2DM patients and healthy controls (P
      < 0.001). The BChE-K genotype showed similar prevalence in T2DM and healthy
      individuals, excluding this genotype as a risk factor for T2DM. However, the
      activity differences remained unexplained. Previous results from our laboratory
      have shown BChE to attenuate the formation of beta-amyloid fibrils, and protect
      cultured neurons from their cytotoxicity. Therefore, we next studied the in vitro
      interactions between recombinant human butyrylcholinesterase and amylin by
      surface plasmon resonance, Thioflavine T fluorescence assay and cross-linking,
      and used cultured pancreatic beta cells to test protection by BChE from amylin
      cytotoxicity. We demonstrate that BChE interacts with amylin through its core
      domain and efficiently attenuates both amylin fibril and oligomer formation.
      Furthermore, application of BChE to cultured beta cells protects them from amylin
      cytotoxicity. Taken together, our results suggest that MetS-associated BChE
      increases could protect pancreatic beta-cells in vivo by decreasing the formation
      of toxic amylin oligomers.

PMID- 20807283
TI  - Activation and regulation of store-operated calcium entry.
AB  - The process of store-operated Ca(2+) entry (SOCE), whereby Ca(2+) influx across
      the plasma membrane is activated in response to depletion of intracellular Ca(2+)
      stores in the endoplasmic reticulum (ER), has been under investigation for
      greater than 25 years; however, only in the past 5 years have we come to
      understand this mechanism at the molecular level. A surge of recent
      experimentation indicates that STIM molecules function as Ca(2+) sensors within
      the ER that, upon Ca(2+) store depletion, rearrange to sites very near to the
      plasma membrane. At these plasma membrane-ER junctions, STIM interacts with and
      activates SOCE channels of the Orai family. The molecular and biophysical data
      that have led to these findings are discussed in this review, as are several
      controversies within this rapidly expanding field.

PMID- 20807288
TI  - Assessing the feasibility of collecting health care resource use data from
      general practices for use in an economic evaluation of vocational rehabilitation
      for back pain.

PMID- 20807289
TI  - Organization of diabetes primary care: a review of interventions that delegate
      general practitioner tasks to a nurse.

PMID- 20807290
TI  - Relationship between total hip replacement appropriateness and surgical priority
      instruments.
AB  - RATIONALE: Variability in indications for total hip replacement (THR) and unequal
      waiting times may limit health care access. OBJECTIVE: To analyse the
      relationship between appropriateness and previously developed surgical priority
      instruments. METHOD: Multicentre cross-validation study of patients placed on the
      waiting list for THR. Information on surgical priority, surgeons' evaluation of
      priority through a visual analogue scale (VAS) and health-related quality of life
      (HRQOL) (Health Utilities Index mark 3, EQ-5D, Western Ontario McMaster
      Osteoarthritic Index) was collected. THR indications were considered appropriate,
      uncertain or inappropriate according to appropriateness criteria. Statistical
      differences and clinically important differences in surgical priority, VAS and
      HRQOL between appropriateness categories were analysed with the Mann-Whitney U
      test and effect size (ES), respectively. Surgical priority score's ability to
      discriminate appropriate and inappropriate indications was evaluated through the
      area under the receiver-operating characteristic curve (AUC) and its 95%
      confidence interval (95% CI). RESULTS: 49.4% (87) of the THR indications were
      deemed appropriate, 39.8% (70) uncertain and 10.8% (19) inappropriate.
      Differences in surgical priority score, VAS and HRQOL between appropriateness
      categories were statistically significant. Clinically important differences were
      generally small (ES, 0.2-0.5) between inappropriate and uncertain, moderate (ES,
      0.5-0.8) between uncertain and appropriate, and large (ES > 0.8) between
      inappropriate and appropriate categories. The AUC to discriminate appropriate and
      inappropriate indications was 0.97 (95% CI: 0.96-0.99) and 0.90 (95% CI: 0.83
      0.97), respectively. CONCLUSIONS: The relationship between the surgical priority
      and appropriateness instruments reinforces their validity and could improve
      waiting list management by establishing maximum waiting periods based on
      patients' characteristics.

PMID- 20807291
TI  - Initiation of antipsychotic treatment by general practitioners. a case-control
      study.
AB  - RATIONALE, AIMS AND OBJECTIVES: Antipsychotics are approved treatment for severe
      conditions and have serious side effects. Antipsychotics are often prescribed off
      label. Although a substantial proportion of antipsychotics are prescribed in
      primary care, it is largely unknown what motivates the general practitioner (GP)
      to initiate antipsychotic treatment. Therefore, we sought to examine the relation
      between pre-defined, licensed as well as off-label, reasons for antipsychotic
      treatment and the initiation of this treatment by the GP as well as report
      registration and incidence of antipsychotic treatment in general practice.
      METHODS: In a case-control study, 723 patients selected from an electronic
      database and with a new antipsychotic prescription were compared with 3615
      controls receiving any other new prescription. Using logistic regression, six pre
      defined categories of International Classification of Primary Care (ICPC) codes
      ('psychosis', 'depression and anxiety', 'sleeping disorders', 'acute stress and
      surmenage', 'dementia' and 'somatic indications') were associated with initiating
      antipsychotic treatment. RESULTS: All, including off-label, categories were
      significantly related to initiating antipsychotic treatment. The incidence of
      initiating antipsychotic therapy was 1.28 per 1000 persons per year (95%
      confidence interval: 1.09, 1.48). GPs registered an ICPC code in 50% and
      prescribed typical antipsychotics in 90% of the cases. Prescription of atypical
      antipsychotics increased almost threefold over the study period. CONCLUSIONS: The
      results suggest that GPs prescribe antipsychotics off-label. Despite serious side
      effects and relatively infrequent occurrence in Dutch general practices, GPs seem
      imprecise in underpinning and registrating the initiation of antipsychotic
      treatment. GPs increasingly prescribe atypical antipsychotics although the
      prescription of typical antipsychotics still dominates.

PMID- 20807292
TI  - How does front-line staff feel about the quality and accessibility of mental
      health services for adults with learning disabilities?

PMID- 20807293
TI  - What influences pre-hospital cannulation intentions in paramedics? An application
      of the theory of reasoned action.
AB  - BACKGROUND: Intravenous cannulation is a common and important intervention
      undertaken by paramedics for administration of fluids and drugs in the pre
      hospital setting. This study was a partial application of the theory of reasoned
      action to the prediction of pre-hospital cannulation intentions as part of an
      evaluation of an educational intervention to change cannulation behaviour in
      paramedics in line with national guidance. METHODS: In 2008 a self-completion
      questionnaire was sent to paramedics from Nottinghamshire and Lincolnshire
      divisions of East Midlands Ambulance Service NHS Trust, UK. This included
      measures of prior behaviour related to cannulation, attitude towards cannulation,
      normative influence related to cannulation and intention to cannulate as well as
      demographic information. RESULTS: Of the 323 paramedics sent questionnaires 137
      (42.2%) responded. Attitude towards cannulation (but not normative or peer
      influence) was a necessary factor for prediction of intention to cannulate in
      respondents. Past cannulation behaviour was indirectly related to intention to
      cannulate through the mediation of attitude towards cannulation. CONCLUSION: The
      theory of reasoned action provides a parsimonious way to predict intentions to
      cannulate. This study suggests that design and evaluation of interventions to
      reduce inappropriate cannulation should be targeted towards changing attitudes of
      paramedics, rather than towards addressing behavioural norms. Future research
      could utilize social-psychological theories to better understand clinical
      behaviour prior to implementation of complex educational or organizational
      interventions.

PMID- 20807294
TI  - The use of statistical process control (risk-adjusted CUSUM, risk-adjusted RSPRT
      and CRAM with prediction limits) for monitoring the outcomes of out-of-hospital
      cardiac arrest patients rescued by the EMS system.
AB  - OBJECTIVE: Based on previous experience from surgical surveillance, risk-adjusted
      cumulative sum (CUSUM)-type charts were applied to monitor out-of-hospital
      cardiac arrest (OHCA) patient mortality. MATERIALS AND METHODS: Data from 2356
      OHCA patients were collected by the Taipei County Fire Bureau from June 2006 to
      November 2007. Logistic regression analysis was applied to create a risk-adjusted
      model. Next, a risk-adjusted CUSUM chart, a risk-adjusted resetting sequential
      probability ratio test chart and a cumulative risk-adjusted mortality with
      prediction limits chart were used to detect excess deaths of the OHCA patients
      rescued by the emergency medical service (EMS) system. RESULTS: The overall
      mortality rate, defined as having no return of spontaneous circulation, was
      79.3%. These three charts signalled an increase in the death rate at similar
      sites, and also suggested a small process shift. CONCLUSION: A visual approach to
      EMS systems monitoring that combines the risk-adjusted cumulative sum, Risk
      adjusted resetting sequential probability ratio test and cumulative risk-adjusted
      mortality with prediction limits charts was established. It was found that this
      approach can be effectively used by the EMS community to monitor OHCA outcomes in
      real time.

PMID- 20807295
TI  - Pharmacist-led intervention study to improve inhalation technique in asthma and
      COPD patients.
AB  - RATIONAL AND AIMS: Inhaled therapy is the mainstay of treatment in patients with
      asthma and chronic obstructive pulmonary disease (COPD). For effectiveness of
      pharmacotherapy, correct use of medication is required. The aims of this study
      were to survey the quality of inhalation technique in patients and to determine
      the effect of a single intervention in community pharmacies by means of
      standardized procedures. METHODS: A total of 757 patients with asthma or COPD
      were randomly selected by 55 community pharmacies. At baseline, patients were
      interviewed and their inhalation technique was assessed with a 21-items
      checklist. Any error was recorded and, if necessary, patients were instructed in
      the proper use of their device. After 4-6 weeks, demonstration of inhalation
      technique was repeated in the community pharmacies and a pre-post comparison was
      performed. RESULTS: A total of 597 patients (78.9%) made at least one mistake in
      performing the inhalation technique at baseline. This number dropped to 214
      (28.3%) from the first to the second appointment. All patients did benefit from
      the pharmacists' intervention regardless of their former training experiences.
      CONCLUSIONS: Inhalation technique of asthma and COPD patients is poor. In daily
      practice, community pharmacy-based pharmacists are well suited to significantly
      supplement doctor-based education in inhalation technique.

PMID- 20807296
TI  - Conventional and advanced time series estimation: application to the Australian
      and New Zealand Intensive Care Society (ANZICS) adult patient database, 1993
      2006.
AB  - RATIONALE: Time series analysis has seen limited application in the biomedical
      Literature. The utility of conventional and advanced time series estimators was
      explored for intensive care unit (ICU) outcome series. METHODS: Monthly mean time
      series, 1993-2006, for hospital mortality, severity-of-illness score (APACHE
      III), ventilation fraction and patient type (medical and surgical), were
      generated from the Australia and New Zealand Intensive Care Society adult patient
      database. Analyses encompassed geographical seasonal mortality patterns, series
      structural time changes, mortality series volatility using autoregressive moving
      average and Generalized Autoregressive Conditional Heteroscedasticity models in
      which predicted variances are updated adaptively, and bivariate and multivariate
      (vector error correction models) cointegrating relationships between series.
      RESULTS: The mortality series exhibited marked seasonality, declining mortality
      trend and substantial autocorrelation beyond 24 lags. Mortality increased in
      winter months (July-August); the medical series featured annual cycling, whereas
      the surgical demonstrated long and short (3-4 months) cycling. Series structural
      breaks were apparent in January 1995 and December 2002. The covariance stationary
      first-differenced mortality series was consistent with a seasonal autoregressive
      moving average process; the observed conditional-variance volatility (1993-1995)
      and residual Autoregressive Conditional Heteroscedasticity effects entailed a
      Generalized Autoregressive Conditional Heteroscedasticity model, preferred by
      information criterion and mean model forecast performance. Bivariate
      cointegration, indicating long-term equilibrium relationships, was established
      between mortality and severity-of-illness scores at the database level and for
      categories of ICUs. Multivariate cointegration was demonstrated for {log APACHE
      III score, log ICU length of stay, ICU mortality and ventilation fraction}.
      CONCLUSIONS: A system approach to understanding series time-dependence may be
      established using conventional and advanced econometric time series estimators.

PMID- 20807297
TI  - Improving diabetes care in a public hospital medical clinic: report of a
      completed audit cycle.
AB  - RATIONALE, AIMS AND OBJECTIVES: To evaluate the impact of clinical audit on
      diabetes care provided to type 2 diabetic patients attending our hospital general
      medical clinics. METHODS: Performances on diabetes-related process measures and
      intermediate outcome measures were evaluated through structured review of
      outpatient medical records. The results were fed back to the doctors and measures
      were implemented to improve care. The performance indicators were re-evaluated 2
      years later to complete the audit cycle. RESULTS: Annual testing rates improved
      for HbA1c (68.4% vs. 87.4%; P < 0.001) and lipid profile (91.8% vs. 97%; P =
      0.027). Enquiry on smoking improved from 45.9% to 82.3% (P < 0.001), eye
      screening rates from 68.9% to 78.8% (P = 0.020) and foot examinations from 22.4%
      to 64.1% (P < 0.001). Prescription rates for insulin increased from 17.3% to
      31.8% (P = 0.001) and statin from 83.2% to 94.4% (P < 0.001). The use of aspirin
      (80.6% vs. 83.8%; P =0.402) and angiotensin-converting enzyme
      inhibitor/angiotensin receptor blocker (92.3% vs. 88.9%; P = 0.239) remained high
      in both cycles. More patients achieved targets for HbA1c < 7% (38% vs. 26%; P =
      0.006), blood pressure < 130/80 mmHg (43% vs. 32%; P = 0.071) and low-density
      lipoprotein cholesterol < 2.6 mmol/L (71% vs. 52%; P <0.001). CONCLUSION:
      Clinical audit is a useful tool in improving diabetes care.

PMID- 20807298
TI  - Improving the quality of drug error reporting.
AB  - BACKGROUND: Drug errors are a common and persistent problem in health care and
      are also associated with serious adverse events. Reporting has become the
      cornerstone of learning from errors, but is not without its imperfections. AIM:
      The aim of this study is to improve reporting and learning from drug errors
      through investigating the contributory factors in drug errors and quality of
      reporting in an acute hospital. METHODS: A retrospective, random sample of 991
      drug error reports from 1999 to 2003 were subjected to quantitative and
      qualitative analysis. This was followed by 40 qualitative interviews with a
      volunteer, multi-disciplinary sample of health professionals. The combined
      analysis has been used to develop a knowledge base for improved drug error
      reporting. RESULTS: The quality of reports varied considerably, and 27% of
      reports lacked any contributory factors. Documentary analysis revealed a focus on
      individuals, sometimes culminating in blame without obvious justification.
      Doctors submitted few reports, and there were notable differences in reporting
      according to clinical location. Communication difficulties commonly featured in
      causation, and high workload and interruptions were predominant contributory
      factors in the interview data. Interviewees viewed causation as multifactorial,
      including cognitive and psychosocial factors. Organizational orientation to error
      was predominantly perceived by interviewees as individual rather than systems
      based. Staff felt obliged to report but rarely received feedback. IMPLICATIONS
      AND CONCLUSION: Drug errors are multifactorial in causation. Current reporting
      schemes lack a theoretical basis, and are unlikely to capture the information
      required to ensure learning about causation. Health professionals have reporting
      fatigue and some remain concerned that reporting promotes individual blame rather
      than an examination of systems factors. Reporting can be strengthened by human
      error theory, redesigned to capture a range of contributory factors, facilitate
      learning and foster supportive actions. It can also be feasible in routine
      practice. Such an approach should be examined through multi-centred evaluation.

PMID- 20807299
TI  - Factorial structure of the perception of risk factors for type 2 diabetes scale:
      exploratory and confirmatory factor analyses.
AB  - RATIONALE, AIMS AND OBJECTIVES: The extent to which individuals' perceptions of
      risk for type 2 diabetes are related to their actual risks and health-promoting
      behaviours is not well known. Yet perception of risk for type 2 diabetes may
      influence the likelihood that individual would engage in preventive behaviours.
      The purpose of this study was to evaluate the psychometric properties of the
      perception of risk factors for type 2 diabetes (PRF-T2DM). METHODS: A
      descriptive, correlational, methodological design was used to conduct this study.
      The sample consisted of 629 adults from 42 states of the United States. A
      demographic questionnaire, the PRF-T2DM, the health-promoting lifestyle profile
      II and the depressive cognition scale were used to collect the data. Data
      analyses consisted of descriptive statistics, scale and item analyses, Pearson's
      correlation analysis, and exploratory and confirmatory factor analyses. RESULTS:
      The PRF-T2DM has a Cronbach's alpha of 0.81. Both extracted factors had
      Cronbach's alphas of 0.74 and 0.80, respectively. Most inter-item and item-to
      total correlation coefficients for factor 1 and factor 2 met the recommended
      criteria of r=0.30 to r=0.70. The PRF-T2DM achieved all minimum recommended
      criteria for model fit (chi(2) /d.f.=2.33, goodness of fit index=0.95, adjusted
      goodness of fit index=0.93, comparative fit index=0.94, root mean square error of
      approximation=0.05, root mean residual=0.05 and the P value for test of close
      fit=0.33). CONCLUSIONS: All statistical estimates and measures of model fit were
      above the standard recommended criteria. The scale has potential uses in research
      and clinical practice. Further development and psychometric evaluation of the PRF
      T2DM is warranted.

PMID- 20807300
TI  - Multiple morbidity is associated with increased problems of food access in
      hospital: a cross-sectional survey utilising the Cumulative Illness Rating Scale.
AB  - BACKGROUND:   Problems of undernutrition are common in hospital in-patients.
      Multiple morbidity increases with age and may contribute to nutritional risks.
      This research aimed to determine whether increased burden of long-term conditions
      is associated with patients' difficulties gaining access to food in hospital.
      METHODS:   A survey was implemented in 29 wards at four hospitals using a
      questionnaire measure of patients' experiences of food access and the Cumulative
      Illness Rating Scale (CIRS) to evaluate the burden of long-term illness in each
      patient. Experiences of food access were evaluated in relation to CIRS score
      category using random effects logistic regression to adjust for age group, sex
      and clustering by ward. RESULTS:   Data were analysed for 764/1154 (66%) eligible
      participants, including 384 women. The median age was 60 years (range 18-96
      years). CIRS scores were analysed using the categories 0 (104 patients), 1-3
      (197), 4-6 (285), 7-9 (144) and >=10 (34). When the CIRS was zero, 10% of
      patients experienced physical problems with food access, whereas, when the CIRS
      was >=10, 41% experienced physical barriers to food access, adjusted odds ratio
      3.65 (1.14-11.7, P = 0.029). Problems with food quality were experienced by 13%
      with CIRS = 0 and 32% with CIRS >= 10 (adjusted odds ratio 3.97, 1.35-11.6, P =
      0.012). Participants with greater morbidity were more likely to report that
      depression, breathing difficulties or chewing and swallowing difficulties
      affected the amount of food that they ate at mealtimes. CONCLUSIONS:   Patients
      with multiple morbidities are more vulnerable to experiencing physical barriers
      to accessing food and increased concerns with food quality. Assessing barriers to
      food access is particularly important in multiple morbidity.

PMID- 20807301
TI  - Sociodemographic and economic characteristics associated with dairy intake vary
      across genders.
AB  - BACKGROUND: Recommendations promote a diversified and optimal but not excessive
      consumption of dairy products. Their efficiency may depend on sociodemographic
      and economic factors, for which little information is available. Links between
      these factors and dairy intake were investigated in a large sample of French
      adults. METHODS: Dietary intakes were assessed using at least six 24-h dietary
      records collected during a 2-year period from 4574 adults aged 45-60 years. The
      cost of each food item was estimated from national data. Sociodemographic and
      economic characteristics were assessed by self-administered questionnaires.
      Compliance with the current dairy recommendation, distribution of the dairy
      budget and calcium inadequacy were compared by logistic regression and covariance
      analyses. RESULTS: Thirty-five percent of subjects complied with the three-per
      day dairy recommendation, with more men than women exceeding this (36.2% versus
      26.5%, P < 0.0001). The proportion of the dairy budget spent on milk increased
      with age in men (P = 0.002); in women, it was inversely associated with
      occupational category (P = 0.009) and residence in an urban area (P = 0.0001).
      The proportion of this budget spent on cheese increased with education level in
      women (P = 0.04) and decreased with age in men (P = 0.03). In men, the
      consumption of cream desserts decreased with age (P = 0.006) and education level
      (P = 0.002). Dietary calcium inadequacy was more prevalent in women than in men
      (32.7% versus 14.2%, P < 0.0001). Among women, this prevalence was higher in
      older subjects (P < 0.0001) and those who lived alone (P = 0.005). CONCLUSIONS:
      Although compliance with dairy recommendation needs to be improved,
      sociodemographic and economic factors should be taken into account to improve the
      efficiency of targeted public health messages.

PMID- 20807302
TI  - A qualitative study comparing commercial and health service weight loss groups,
      classes and clubs.
AB  - BACKGROUND: Group-based interventions for weight loss are popular; however,
      little is known about how health service groups compare with the commercial
      sector, from either the participant or the group leader perspective. Currently,
      health professionals have little guidance on how to deliver effective group
      interventions. The present study aimed to compare and contrast leaders' and
      attendees' experiences of health service and commercial weight loss groups,
      through in-depth interviews and group observations. METHODS: Purposive sampling,
      guided by a sampling frame, was employed to identify diverse groups operating in
      Scotland with differing content, structures and style. Data collection and
      analysis took place concurrently in accordance with a grounded theory approach.
      Thirteen semi-structured group observations and in-depth audio-recorded
      interviews with 11 leaders and 22 attendees were conducted. Identification of
      themes and the construction of matrices to identify data patterns were guided by
      the Framework Method for qualitative analysis. RESULTS: Compared to commercial
      groups, health service 'groups' or 'classes' tended to offer smaller periodic
      fixed term groups, involving gatekeeper referral systems. Commercial
      organisations provide a fixed branded package, for 'club' or 'class' members, and
      most commercial leaders share personal experiences of losing weight. Health
      service leaders had less opportunity for supervision, peer support or specific
      training in how to run their groups compared to commercial leaders. CONCLUSIONS:
      Commercial and health service groups differ in access; attendee and leader
      autonomy; engagement in group processes; and approaches to leadership and
      training, which could influence weight loss outcomes. Health service groups can
      provide different group content and experiences, particularly for those with
      chronic diseases and for populations less likely to attend commercial groups,
      such as men.

PMID- 20807304
TI  - Subtelomeric rearrangements and copy number variations in people with
      intellectual disabilities.
AB  - BACKGROUND: The most prevalent type of structural variation in the human genome
      is represented by copy number variations that can affect transcription levels,
      sequence, structure and function of genes. METHOD: In the present study, we used
      the multiplex ligation-dependent probe amplification (MLPA) technique and
      quantitative PCR for the detection of copy number variation in 132 intellectually
      disabled male patients with normal karyotypes and negative fragile-X-testing.
      RESULTS: Ten of these patients (7.6%) showed copy number variation in the
      subtelomeric regions, including deletions and duplications. DISCUSSION:
      Duplications of the SECTM1 gene, located at 17q25.3, and of the FLJ22115 gene,
      located at 20p13, could be associated with phenotype alterations. This study
      highlights the relevance in the aetiology of intellectual disability of
      subtelomeric rearrangements that can be screened by MLPA and other molecular
      techniques.

PMID- 20807303
TI  - Green tea improves metabolic biomarkers, not weight or body composition: a pilot
      study in overweight breast cancer survivors.
AB  - BACKGROUND: Overweight status after breast cancer treatment may increase a
      woman's risk for recurrent disease and/or early onset cardiovascular disease.
      Green tea has been proposed to promote weight loss and favourably modify glucose,
      insulin and blood lipids. This pilot study tested the effect of daily
      decaffeinated green tea consumption for 6 months on weight and body composition,
      select metabolic parameters and lipid profiles in overweight breast cancer
      survivors. METHODS: The effect of daily decaffeinated green tea intake on weight,
      body composition and changes in resting metabolic rate, energy intake, glucose,
      insulin, homeostasis model assessment--insulin resistance (HOMA-IR) and lipids
      was evaluated in overweight breast cancer survivors. Participants had a mean
      weight of 80.2 kg; body mass index (BMI) 30.1 kg m-2; and body fat 46.4%.
      Participants (n = 54) were randomised to 960 mL of decaffeinated green or placebo
      tea daily for 6 months. RESULTS: Mean (SD) tea intake among study completers (n =
      39) was 5952 (1176) mL week-1 and was associated with a significant reduction in
      energy intake (P = 0.02). Change in body weight of -1.2 kg (green tea) versus
      +0.2 kg (placebo) suggests a weight change effect, although this was not
      statistically significant. Decaffeinated green tea intake was associated with
      elevated high-density lipoprotein (HDL) levels (P = 0.003) and nonsignificant
      improvements in the HDL/LDL ratio and HOMA-IR (-1.1 +/- 5.9: green tea; +3.2 +/-
      7.2: herbal). CONCLUSIONS: Intake of decaffeinated green tea for 6 months was
      associated with a slight reduction in body weight and improved HDL and glucose
      homeostasis in overweight breast cancer survivors.

PMID- 20807305
TI  - Randomized clinical trial on short-time compression with Kaolin-filled pad: a new
      strategy to avoid early bleeding and subacute radial artery occlusion after
      percutaneous coronary intervention.
AB  - BACKGROUND: Despite the increasing use of transradial techniques for cardiac
      percutaneous procedures, none of the strategies commonly utilized for hemostasis
      has been able to reduce the occurrence of radial artery occlusion (RAO). The aim
      of this study was to evaluate the occurrence of 24-hour RAO and the rate of
      bleeding of a novel hemostatic device for radial closure after percutaneous
      interventions, in adjunct to short-time compression. METHODS: Once the radial
      access was obtained, patients were randomized to 3 different strategies of radial
      closure: a short compression with the QuikClot(r) InterventionalTM pad (Z-Medica
      Corporation, Wallingford, CT, USA) (15 minutes, group 1), a short compression (15
      minutes, group 2), and a conventional prolonged compression (2 hours, group 3)
      both without QuikClot(r) utilization. RESULTS: Fifty patients in group 1, 20 in
      group 2, and 50 in group 3 were enrolled. The three groups were homogenous for
      baseline and procedural characteristics. None of patients in group 1 developed
      RAO, 1 (5%) occurred in group 2, and 5 (10%) in group 3 (P = 0.05). Active
      bleeding after compression removal occurred in 10 patients (20%) in group 1, 18
      (90%) in group 2, and 1 (2%) in group 3 (P < 0.001). Among patients in group 1,
      at univariate analysis, the predictors of acute bleeding resulted in chronic
      therapy with clopidogrel (Odds Ratio 28.78, 95% Confidence Intervals 4.79-172.82,
      P < 0.001) and high levels of activated clotting time (ACT) at the time of sheath
      removal (OR 1.02, 95% CI 1.00-1.03, P = 0.009). At ROC analysis, the cutoff value
      of ACT for the risk of bleeding with a sensitivity of 80% and specificity of 75%
      was 287 seconds. CONCLUSIONS: Early sheet removal and short-time compression with
      QuikClot(r) InterventionalTM can reduce the rate of RAO after diagnostic or
      interventional procedures especially in patients not on double antiplatelet
      therapy.

PMID- 20807306
TI  - Rescue angioplasty: characteristics and results in a single-center experience.
AB  - PURPOSE AND METHODS: Rescue angioplasty (RA) has demonstrated its efficacy for
      the treatment of failed thrombolysis after acute myocardial infarction (AMI). We
      analyzed clinical, angiographic, and procedural characteristics, and prognosis at
      30 days of prospective cohort of unselected patients admitted for RA. RESULTS:
      From August 2004 to August 2009, 361 patients were included in a single center.
      The median time pain to the thrombolysis was 140 minutes (interquartile range
      [IQR] 90-210), delay transfer 100 minutes (IQR 65-120); pain to PCI was 330
      minutes (IQR 270-400). Initial flow TIMI 3 (Thrombolysis in Myocardial
      Infarction) was presented in 102 (28.3%) of cases and blush grade 3 in 88
      (24.4%). After the procedure, TIMI 3 flow was achieved in 286 (79.2%) and blush
      grade 3 in 256 (71%) (P < 0.001 and P < 0,001, respectively). A glycoprotein
      IIb/IIIa receptor inhibitor (Abciximab) was used in 115 patients (32%). Stents
      were implanted in 339 (94%) of patients, 137 (38%) of which were drug-eluting
      stent. Complete ST segment resolution was observed in 202 (64.5%) patients in 12
      lead electrocardiogram (ECG) and procedural success was 77.6%. Adverse cardiac
      events and death after 30 days follow-up were 13.6% and 10.7%, respectively.
      Target vessel revascularization at 30 days was 1.9%. CONCLUSIONS: Routine
      application of RA in patients with persistent ST elevation 90 minutes after
      thrombolysis is a useful technique for achieving revascularization of the
      affected artery. In-hospital mortality remains high especially in patients with
      cardiac shock, despite new interventional techniques available, and adjunctive
      antithrombotic therapy.

PMID- 20807308
TI  - Photoreceptor rescue and toxicity induced by different calpain inhibitors.
AB  - Photoreceptor degeneration is the hallmark of a group of inherited blinding
      diseases collectively termed retinitis pigmentosa (RP); a major cause of
      blindness in humans. RP is at present untreatable and the underlying
      neurodegenerative mechanisms are largely unknown, even though the genetic causes
      are often established. The activation of calpain-type proteases may play an
      important role in cell death in various neuronal tissues, including the retina.
      We therefore tested the efficacy of two different calpain inhibitors in
      preventing cell death in the retinal degeneration (rd1) human homologous mouse
      model for RP. Pharmacological inhibition of calpain activity in rd1 organotypic
      retinal explants had ambiguous effects on photoreceptor viability. Calpain
      inhibitor XI had protective effects when applied for short periods of time (16 h)
      but demonstrated substantial levels of toxicity in both wild-type and rd1 retina
      when used over several days. In contrast, the highly specific calpain inhibitor
      calpastatin peptide reduced photoreceptor cell death in vitro after both short
      and prolonged exposure, an effect that was also evident after in vivo application
      via intravitreal injection. These findings highlight the importance of calpain
      activation for photoreceptor cell death but also for photoreceptor survival and
      propose the use of highly specific calpain inhibitors to prevent or delay RP.

PMID- 20807309
TI  - Are current disease-modifying therapeutics in multiple sclerosis justified on the
      basis of studies in experimental autoimmune encephalomyelitis?
AB  - The precise aetio-pathology of multiple sclerosis remains elusive. However,
      important recent advances have been made and several therapies have been licensed
      for clinical use. Many of these were developed, validated or tested in the animal
      model, experimental autoimmune encephalomyelitis (EAE). This systematic review
      aims to assess whether the current disease modifying treatments and those that
      are the closest to the clinic are justified on the basis of the results of EAE
      studies. We discuss some aspects of the utility and caveats of EAE as a model for
      multiple sclerosis drug development.

PMID- 20807310
TI  - Roles of two subtypes of corticotrophin-releasing factor receptor in the
      corticostriatal long-term potentiation under cocaine withdrawal condition.
AB  - The roles of two subtypes of corticotrophin-releasing factor (CRF) receptor in
      corticostriatal synaptic plasticity under cocaine withdrawal condition were
      examined in this study. Neither the resting membrane potential and input
      resistance of striatal neurons nor the long-term potentiation (LTP) of
      corticostriatal slices were affected by cocaine withdrawal. CRF dose-dependently
      enhanced in vitro corticostriatal LTP in rats from both cocaine-withdrawal and
      saline-control groups. Yet, the enhancement of corticostriatal LTP by CRF (20,
      40, 80 nM) was significantly greater in the cocaine-withdrawal group than in the
      control group. CRF(1)-selective antagonist (NBI 27914, 100 nM) attenuated the CRF
      induced enhancement of corticostriatal LTP in both groups, whereas the CRF(2)
      selective antagonist (astression2B, 100 nM) attenuated the enhanced
      corticostriatal LTP only in the cocaine-withdrawal group. Importantly, urocortin2
      (a CRF(2)-selective agonist, 40 nM) selectively increased corticostriatal LTP in
      the cocaine-withdrawal group, but not in the saline controls. The urocortin2
      induced enhancement of LTP was totally blocked by astression2B (100 nM). These
      results suggest that the CRF system modulate neuroadaptive changes in the
      corticostriatal circuit during cocaine withdrawal, and the CRF(2) in this area
      mediate an important mechanism that contributes to the relapse of cocaine
      addiction.

PMID- 20807312
TI  - Neuronal over-expression of chromogranin A accelerates disease onset in a mouse
      model of ALS.
AB  - Recent studies provided evidence that chromogranins can interact with mutant
      superoxide dismutase 1 (SOD1) and that chromogranin B (CgB) may act as a
      susceptibility gene and modifier of onset in amyotrophic lateral sclerosis (ALS).
      To further investigate the role of chromogranins in ALS pathogenesis, we
      generated SOD1(G37R) mice that over-express CgA under the control of Thy1
      promoter. Here, we report that neuronal over-expression of CgA in SOD1(G37R) mice
      caused acceleration of onset of motor impairment and exacerbation of motor neuron
      degeneration. The use of monoclonal antibody specific to misfolded mutant SOD1
      demonstrated a higher level of misfolded SOD1 species in double transgenic mice
      compared to SOD1(G37R) mice, suggesting a stabilization of pathogenic SOD1
      species by excess CgA. These results suggest a role of chromogranins as
      modulators of disease onset in ALS pathogenesis.

PMID- 20807311
TI  - Role of adenosine and wake-promoting basal forebrain in insomnia and associated
      sleep disruptions caused by ethanol dependence.
AB  - Insomnia is a severe symptom of alcohol withdrawal; however, the underlying
      neuronal mechanism is yet unknown. We hypothesized that chronic ethanol exposure
      will impair basal forebrain (BF) adenosinergic mechanism resulting in insomnia
      like symptoms. We performed a series of experiments in Sprague-Dawley rats to
      test our hypothesis. We used Majchrowicz's chronic binge ethanol protocol to
      induce ethanol dependency. Our first experiment verified the effects of ethanol
      withdrawal on sleep-wakefulness. Significant increase in wakefulness was observed
      during ethanol withdrawal. Next, we examined c-Fos expression (marker of neuronal
      activation) in BF wake-promoting neurons during ethanol withdrawal. There was a
      significant increase in the number of BF wake-promoting neurons with c-Fos
      immunoreactivity. Our third experiment examined the effects of ethanol withdrawal
      on sleep deprivation induced increase in BF adenosine levels. Sleep deprivation
      did not increase BF adenosine levels in ethanol dependent rats. Our last
      experiment examined the effects of ethanol withdrawal on equilibrative nucleoside
      transporter 1 and A1 receptor expression in the BF. There was a significant
      reduction in A1 receptor and equilibrative nucleoside transporter 1 expression in
      the BF of ethanol dependent rats. Based on these results, we suggest that
      insomnia observed during ethanol withdrawal is caused because of impaired
      adenosinergic mechanism in the BF.

PMID- 20807314
TI  - Dilysine retrieval signal-containing p24 proteins collaborate in inhibiting gamma
      cleavage of amyloid precursor protein.
AB  - gamma-Secretase mediates intramembranous gamma-cleavage and epsilon-cleavage of
      beta-amyloid precursor protein (APP) to liberate beta-amyloid peptide (Abeta) and
      APP intracellular domain respectively from the membrane. Although the regulatory
      mechanism of gamma-secretase cleavage remains unresolved, a member of the p24
      cargo protein family, named p24delta(1) or TMP21, has been identified as an
      activity-modulating component. The p24 family proteins are divided into four
      subfamilies (p24alpha, beta, delta and gamma). In contrast to p24delta(1),
      p24beta(1) has reportedly no effect on gamma-cleavage. In this study, we
      determined whether p24alpha(2), p24gamma(3) or p24gamma(4) modulates APP
      processing. Knockdown of cellular p24alpha(2) induced a significant increase in
      Abeta generation but not in APP intracellular domain production in cell-based and
      cell-free assays, whereas p24alpha(2) over-expression suppressed Abeta secretion.
      By contrast, Abeta secretion was not altered by p24gamma(3) or p24gamma(4)
      knockdown. Endogenous p24alpha(2) co-immunoprecipitated with core components of
      the gamma-secretase complex, and the anti-p24alpha(2) immunoprecipitate exhibited
      gamma-secretase activity. Mutational disruption of the conserved dilysine ER
      retrieval motifs of p24alpha(2) and p24delta(1) perturbed inhibition of gamma
      cleavage. Simultaneous knockdown, or co-over-expression, of these proteins had no
      additive or synergistic effect on Abeta generation. Our findings suggest that
      dilysine ER-retrieval signal-containing p24 proteins, p24alpha(2) and
      p24delta(1), bind with gamma-secretase complexes and collaborate in attenuating
      gamma-cleavage of APP.

PMID- 20807313
TI  - Linking cardiometabolic disorders to sporadic Alzheimer's disease: a perspective
      on potential mechanisms and mediators.
AB  - There is increasing evidence that the incidence of Alzheimer's disease (AD) is
      significantly influenced by cardiovascular risk factors in association with a
      cluster of metabolic diseases including diabetes and atherosclerosis. The shared
      risk is also reflected in the dietary and lifestyle links to both metabolic
      disorders and AD-type cognitive dysfunction. Recent studies with genetic and diet
      induced animal models have begun to illuminate convergent mechanisms and
      mediators between these two categories of disease conditions with distinct tissue
      specific pathologies. Although it is clear that peripheral inflammation and
      insulin resistance are central to the pathogenesis of the disorders of metabolic
      syndrome, it seems that the same mechanisms are also in play across the blood
      brain barrier that lead to AD-like molecular and cognitive changes. This review
      highlights these convergent mechanisms and discusses the role of cerebrovascular
      dysfunction as a conduit to brain emergence of these pathogenic processes that
      might also represent future therapeutic targets in AD in common with metabolic
      disorders.

PMID- 20807316
TI  - A specific isoform of glial cell line-derived neurotrophic factor family receptor
      alpha 1 regulates RhoA expression and glioma cell migration.
AB  - Malignant gliomas are highly invasive neuroepithelial tumors where the tendency
      to invade and migrate away from the primary tumor mass is thought to be a leading
      cause of tumor recurrence and treatment failures. Autocrine signals produced by
      secreted factors that signal through receptors on the tumor are known to
      contribute to the invasiveness. Glial cell line-derived neurotrophic factor and
      GDNF family receptor alpha 1 (GFRalpha1) are over-expressed in human gliomas. We
      have previously reported that human gliomas express high levels of GFRalpha1b, an
      alternatively spliced isoform of GFRalpha1. However, the functional significance
      of GFRalpha1b in glioma behaviors is currently unknown. In this study, we have
      designed isoform-specific small-interfering RNA to knockdown the highly
      homologous GFRalpha1a or GFRalpha1b isoform efficiently in malignant C6 glioma
      cells. Unexpectedly, the knockdown of GFRalpha1b but not GFRalpha1a induced cell
      elongation and inhibited C6 cell migration and invasion in vitro. In addition,
      GFRalpha1b was found to regulate the expression of RhoA small GTPase, which was
      required for migration of C6 cells. The decreases in RhoA expression and cell
      migration after GFRalpha1b knockdown were attenuated by small-interfering RNA 
      resistant GFRalpha1b but not GFRalpha1a, further demonstrating the specific role
      of GFRalpha1b in glioma migration. Interestingly, the knockdown of NCAM but not
      receptor tyrosine kinase Ret resulted in the reduction of RhoA expression and C6
      cell migration. Taken together, these unanticipated results indicate that
      GFRalpha1b is involved in glioma migration through glial cell line-derived
      neurotrophic factor -GFRalpha1b-NCAM signaling complex and modulation of RhoA
      expression.

PMID- 20807315
TI  - Niemann-Pick type C disease: molecular mechanisms and potential therapeutic
      approaches.
AB  - Cholesterol is an important lipid of mammalian cells. Its unique physicochemical
      properties modulate membrane behavior and it serves as the precursor for steroid
      hormones, oxysterols and vitamin D. Cholesterol is effluxed from the late
      endosomes/lysosomes via the concerted action of at least two distinct proteins:
      Niemann-Pick C (NPC)1 and NPC2. Mutations in these two proteins manifest as NPC
      disease - a very rare, usually fatal, autosomal, recessive, neurovisceral,
      lysosomal storage disorder. In this review, we discuss the possible mechanisms of
      action for NPC1 and NPC2 in mediating cholesterol efflux, as well as the
      different therapeutic approaches being pursued for the treatment of this lipid
      storage disorder.

PMID- 20807317
TI  - A single prenatal exposure to the endocrine disruptor 2,3,7,8-tetrachlorodibenzo
      p-dioxin alters developmental myelination and remyelination potential in the rat
      brain.
AB  - Polychlorinated dibenzo-dioxins, furans and dioxin-like polychlorinated biphenyls
      are ubiquitous in foodstuffs of animal origin and accumulate in the fatty tissues
      of animals and humans. The most toxic congener is 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD), a lipophilic endocrine-disrupting molecule that accumulates in
      adipose tissue, placenta and milk. polychlorinated biphenyls and TCDD are known
      to interfere with thyroid hormone metabolism and signaling in the developing
      brain. As thyroid hormone is critical in the myelination process during
      development, we investigated the effect of a single dose of TCDD prenatal
      exposure (gestational day 18) on the myelination process. A semi-quantitative
      analysis of oligodendrocyte markers at different stages of maturation was
      performed in the offspring's medulla oblongata, cerebellum, diencephalon and
      telenchephalon at different postnatal days (2/3, 14, 30 and 135). The most
      significant alterations observed were: (i) cerebellum and medulla oblongata:
      altered expression of oligodendroglial lineage and platelet-derived growth factor
      alpha receptor, myelin basic protein (MBP) mRNAs (P2/3, P135) and MBP protein
      (P135); (ii) diencephalon: increase in platelet- derived growth factor alpha
      receptor mRNA level (P2/3); (iii) telenchephalon: decrease in MBP mRNA
      expression. The oligodendroglial generation capability of adult neural
      stem/precursor cells obtained ex vivo from TCDD and vehicle-treated dams was then
      explored. TCDD impairs neurosphere proliferation and retards CNPase-positive cell
      generation from adult neurospheres.

PMID- 20807319
TI  - Expression and regulation of a low-density lipoprotein receptor exon 12 splice
      variant.
AB  - As low-density lipoprotein receptor (LDLR) contributes to cholesterol and amyloid
      beta homeostasis, insights into LDLR regulation may facilitate our understanding
      of cardiovascular disease and Alzheimer's disease. Previously, we identified LDLR
      isoforms that lacked exon 12 or exons 11-12 and that are predicted to encode
      soluble, dominant negative, LDLR. Moreover, these isoforms were associated with
      rs688, an exon 12 polymorphism that was associated with LDL-cholesterol and
      Alzheimer's disease risk. In this study, we present evidence that although the
      truncated LDLR isoforms are translated in vitro, they represent < 0.1% of CSF
      proteins. As these LDLR isoforms likely represent a loss of mRNA-encoding
      functional LDLR, we then focused upon identifying intron-exon boundary and exonic
      splicing enhancer elements critical to splicing. Exon 12 inclusion is enhanced by
      altering the 5' splice site in intron 12 towards a consensus splice donor
      sequence, consistent with its being a weak 5' splice site. Additionally, of the
      nine evolutionarily conserved putative splicing enhancer regions within exon 12,
      two regions that flank rs688 were critical to exon 12 inclusion. Overall, these
      results suggest that LDLR splice variants represent a loss of mRNA encoding
      functional LDLR and provide insights into the regulatory elements critical for
      LDLR exon 12 splicing.

PMID- 20807321
TI  - Recurrent postcoital hematuria. A case of fibroepithelial urethral polyp in an
      adult female.
AB  - INTRODUCTION: In males, an isolated gross postcoital hematuria is a very rare
      clinical phenomenon. No cases of postcoital macroscopic hematuria have been
      previously reported in females. AIM: To report a case of female urethral
      fibroepithelial polyp (FEP) associated with recurrent postcoital hematuria.
      METHODS: A young (31 years old), eumenorrheic woman complained of three episodes
      of postcoital macrohematuria. The patient was assessed with a detailed history,
      with a bimanual pelvic examination and with bidimensional and tridimensional
      ultrasonographic and color Doppler analyses of the internal genitalia and of the
      urethrovaginal space. MAIN OUTCOMES MEASURES: Transvaginal two-dimensional (2-D)
      ultrasonographic evaluation of internal genitalia, bladder and urethra and three
      dimensional (3-D) analysis of the urethra and paraurethral structures. RESULTS:
      The 2-D transvaginal evaluation and the 3-D reconstruction showed a polypoid
      hypervascularized structure arising from the anterior urethral wall. A
      cystourethroscopy confirmed the presence of a FEP arising from the anterior wall
      of the urethra and allowed its removal. CONCLUSIONS: A gross postcoital hematuria
      may be associated with a urethral polyp. The ultrasonographic evaluation of the
      urethrovaginal space can facilitate the diagnosis.

PMID- 20807320
TI  - Peripheral endocannabinoid system-mediated actions of rimonabant on growth
      hormone secretion are ghrelin-dependent.
AB  - The somatotroph axis is a crucial pathway regulating metabolism. Despite the fact
      that the endocannabinoid system has been also revealed as a potent modulator of
      energy homeostasis, little information is available concerning a putative
      interaction between these two systems. The aim of the present study was to
      determine the in vivo effects of the blockade of the cannabinoid receptor type 1
      (CB1) over growth hormone (GH) secretion using the CB1 antagonist rimonabant. The
      results obtained show that the blockade of the CB1 peripheral receptor by i.p.
      injection of rimonabant significantly inhibited pulsatile GH secretion.
      Similarly, it was found that this injection significantly decreased ghrelin
      induced GH secretion without any effect on growth hormone-releasing hormone
      (GHRH)-induced GH discharge. In situ hybridisation showed that the peripheral
      blockade of CB1 did not affect hypothalamic somatostatin mRNA levels; however,
      GHRH mRNA expression was significantly decreased. The blockade of the vagus nerve
      signal by surgical vagotomy eliminated the inhibitory action of rimonabant on
      GHRH mRNA and consequently on GH. On the other hand, the central CB1 blockade by
      i.c.v. rimonabant treatment was unable to reproduce the effect of peripheral
      blockade on GHRH mRNA, nor the GH response to ghrelin. In conclusion, the data
      reported in the present study establish, from a physiological point of view, the
      existence of a novel mechanism of GH regulation implicating the action of the
      cannabinoid receptor on the somatotroph axis.

PMID- 20807318
TI  - NK-3 receptor antagonism prevents behavioral sensitization to cocaine: a role of
      glycogen synthase kinase-3 in the nucleus accumbens.
AB  - Repeated administration of cocaine induces heightened behavioral hyperactivity
      termed sensitization. Although NK-3 receptors have been shown to modulate acute
      cocaine-induced behaviors, their role in behavioral sensitization is unknown. The
      present study investigated whether NK-3 receptor blockade altered behavioral
      sensitization to cocaine. Additionally, glycogen synthase kinase-3 (GSK3) has
      been shown to be involved in dopamine receptor signaling and in development of
      sensitization; therefore regulation of GSK3 activity in the nucleus accumbens was
      also investigated. Administration of the NK-3 receptor antagonist SB 222200 (5
      mg/kg, s.c.) prior to repeated cocaine (20 mg/kg, i.p.) prevented the development
      of sensitized responses after a cocaine challenge. Pre-treatment with SB 222200
      before a cocaine challenge also blocked expression of sensitization. Decrease in
      GSK3 activity demonstrated by increased phosphorylation of GSK3alpha and GSK3beta
      was detected 20 mins after an acute cocaine injection. In contrast, a cocaine
      challenge failed to alter phosphorylation of GSK3alpha and GSK3beta in sensitized
      mice. SB 222200 prior to repeated cocaine resulted in increased phosphorylation
      of GSK3alpha and GSK3beta akin to changes following acute cocaine. Collectively,
      these findings demonstrate the involvement of NK-3 receptors in development and
      expression of behavioral sensitization and in regulation of GSK3 activity in the
      nucleus accumbens after repeated cocaine.

PMID- 20807322
TI  - Efficacy and safety of an orodispersible vardenafil formulation for the treatment
      of erectile dysfunction in elderly men and those with underlying conditions: an
      integrated analysis of two pivotal trials.
AB  - INTRODUCTION: Men with erectile dysfunction (ED) are typically older and have one
      or more underlying cardiovascular conditions. AIM: To determine the efficacy and
      safety of a new orodispersible tablet (ODT) formulation of vardenafil for the
      treatment of ED, and whether age, or the presence of underlying conditions
      affects treatment outcomes. METHODS: This is an integrated analysis of data from
      two phase III, double-blind, multicenter, randomized, parallel-group, placebo
      controlled studies that compared 10 mg on-demand vardenafil ODT with placebo in a
      general population of men with ED, stratified so that approximately 50% of
      patients were aged >= 65 years. Results were reported by age (<6 5 vs. >= 65
      years) and presence/absence of diabetes, dyslipidemia, or hypertension. MAIN
      OUTCOME MEASURES: Primary measures were the erectile function domain of the
      International Index of Erectile Function (IIEF-EF) and Sexual Encounter Profile
      questions 2 (SEP2) and 3 (SEP3). RESULTS: Of the 701 men randomized (51% aged >=
      65 years), 686 were included in the intent-to-treat population (placebo, n = 334;
      vardenafil ODT, n = 352). Vardenafil ODT was significantly superior to placebo
      for all primary efficacy measures, regardless of age, baseline ED severity, or
      underlying condition (P < 0.0001 for vardenafil vs. placebo for each endpoint).
      IIEF-EF scores and SEP2/3 success rates in older patients and men with underlying
      conditions were not significantly different to those of younger patients or men
      without underlying conditions. Adverse events (AEs) were mostly mild to moderate
      in severity, occurring with higher incidence in the vardenafil vs. placebo group.
      The most frequently reported drug-related AEs in the vardenafil group were
      headache, flushing, nasal congestion, dizziness, and dyspepsia, consistent with
      the known safety profile of phosphodiesterase type 5 inhibitors. CONCLUSIONS:
      Vardenafil ODT significantly improves erectile function in men with ED regardless
      of age, baseline ED severity, or underlying condition.

PMID- 20807323
TI  - Sexual rehabilitation and penile pain associated with intracavernous alprostadil
      after radical prostatectomy.
AB  - INTRODUCTION: Intracavernous alprostadil injection (IAI) is widely used for
      sexual rehabilitation (SR) after radical prostatectomy (RP). However, the rate of
      spontaneous erection recovery with IAI remains unclear, and IAI causes pain that
      may hinder SR. AIMS: To assess SR in IAI users after RP and to evaluate the
      course and impact on SR of postinjection penile pain. METHODS: We prospectively
      studied 87 patients who underwent nerve-sparing laparoscopic RP, reported normal
      preoperative erectile function, and used IAI for 12 months. Patients started with
      2.5 ug alprostadil and were advised to increase the dose gradually until erection
      hardness allowed vaginal penetration. MAIN OUTCOME MEASURES: At 6 and 12 months,
      the International Index of Erectile Function (IIEF-15) and Erection Hardness
      Score (EHS) were determined with and without IAI, and injection-related penile
      pain was assessed using a numeric rating scale. Correlations linking penile pain,
      IIEF-15, and EHS scores were evaluated. RESULTS: The mean alprostadil dose was
      8.1 ug after 6 months and 9.9 ug after 12 months. With/without IAI, mean IIEF-15
      scores for erectile and orgasmic function and mean EHS score were 14.6/4.6,
      4.1/2.1, and 2.5/0.4, respectively, after 6 months; and 17.2/5.4, 4.9/2.6, and
      2.7/0.9 after 12 months. Pain scores were 3.2+/-2.5/10 and 2.5+/-2.5/10 after 6
      and 12 months, respectively. Pain intensity correlated with erectile function (r=
      0.23), intercourse satisfaction (r=-0.23), and overall satisfaction (r=-0.24)
      after 6 months but not after 12 months. Follow-up was short and only patients who
      used IAI for 12 months were included. CONCLUSIONS: In patients who were willing
      and able to use IAI, erectile function improved after 1 year but remained below
      preoperative levels. The adverse impact of pain on SR was significant during the
      first 6 months and diminished over time. These data may help to counsel IAI users
      with painful erections.

PMID- 20807324
TI  - Peptide amphiphile nanofiber delivery of sonic hedgehog protein to reduce smooth
      muscle apoptosis in the penis after cavernous nerve resection.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a serious medical condition that
      affects 16-82% of prostate cancer patients treated by radical prostatectomy and
      current treatments are ineffective in 50-60% of prostatectomy patients. The
      reduced efficacy of treatments makes novel therapeutic approaches to treat ED
      essential. The secreted protein Sonic hedgehog (SHH) is a critical regulator of
      penile smooth muscle and apoptosis that is decreased in cavernous nerve (CN)
      injury and diabetic ED models. Past studies using Affi-Gel beads have shown SHH
      protein to be effective in suppressing apoptosis caused by CN injury. AIM: We
      hypothesize that SHH protein delivered via novel peptide amphiphile (PA)
      nanofibers will be effective in suppressing CN injury-induced apoptosis. METHODS:
      Adult Sprague Dawley rats (n=50) were used to optimize PA injection in vivo. PA
      with SHH protein (n=16) or bovine serum albumin (BSA) (control, n=14) was
      injected into adult rats that underwent bilateral CN cut. Rats were sacrificed at
      2, 4, and 7 days. Alexa Fluor-labeled SHH protein was used to determine the
      target of SHH signaling (n=3). MAIN OUTCOME MEASURES: Terminal deoxynucleotidyl
      transferase dUTP nick end labeling (TUNEL) and semiquantitative
      immunohistochemical analysis for SHH protein and cluster differentiation protein
      three (CD3) were performed. RESULTS: SHH-PA caused a 25% and 16% reduction in
      apoptosis at 4 and 7 days after CN injury and a 9.3% and 19% increase in SHH
      protein at 4 and 7 days after CN injury. CD3 protein was not observed in SHH-PA
      treated penis. In vitro, 73% of SHH protein diffused from PA within 6 days.
      Labeled SHH was observed in smooth muscle. CONCLUSIONS: PA technology is
      effective in delivering SHH protein to the penis and SHH is effective in
      suppressing CN injury-induced apoptosis. These results suggest substantial
      translational potential of this methodology and show that only a short duration
      of SHH treatment is required to impact the apoptotic index.

PMID- 20807326
TI  - Neuroimaging of love: fMRI meta-analysis evidence toward new perspectives in
      sexual medicine.
AB  - INTRODUCTION: Brain imaging is becoming a powerful tool in the study of human
      cerebral functions related to close personal relationships. Outside of
      subcortical structures traditionally thought to be involved in reward-related
      systems, a wide range of neuroimaging studies in relationship science indicate a
      prominent role for different cortical networks and cognitive factors. Thus, the
      field needs a better anatomical/network/whole-brain model to help translate
      scientific knowledge from lab bench to clinical models and ultimately to the
      patients suffering from disorders associated with love and couple relationships.
      AIM: The aim of the present review is to provide a review across wide range of
      functional magnetic resonance imaging (fMRI) studies to critically identify the
      cortical networks associated with passionate love, and to compare and contrast it
      with other types of love (such as maternal love and unconditional love for
      persons with intellectual disabilities). METHODS: Retrospective review of
      pertinent neuroimaging literature. MAIN OUTCOME MEASURES: Review of published
      literature on fMRI studies of love illustrating brain regions associated with
      different forms of love. RESULTS: Although all fMRI studies of love point to the
      subcortical dopaminergic reward-related brain systems (involving dopamine and
      oxytocin receptors) for motivating individuals in pair-bonding, the present meta
      analysis newly demonstrated that different types of love involve distinct
      cerebral networks, including those for higher cognitive functions such as social
      cognition and bodily self-representation. CONCLUSIONS: These metaresults provide
      the first stages of a global neuroanatomical model of cortical networks involved
      in emotions related to different aspects of love. Developing this model in future
      studies should be helpful for advancing clinical approaches helpful in sexual
      medicine and couple therapy.

PMID- 20807325
TI  - Erectile dysfunction in young non-obese type II diabetic Goto-Kakizaki rats is
      associated with decreased eNOS phosphorylation at Ser1177.
AB  - INTRODUCTION: Diabetes mellitus (DM) is a risk factor for erectile dysfunction
      (ED). Although type 2 DM is responsible for 90-95% diabetes cases, type 1 DM
      experimental models are commonly used to study diabetes-associated ED. AIM: Goto
      Kakizaki (GK) rat model is relevant to ED studies since the great majority of
      patients with type 2 diabetes display mild deficits in glucose-stimulated insulin
      secretion, insulin resistance, and hyperglycemia. We hypothesized that GK rats
      display ED which is associated with decreased nitric oxide (NO) bioavailability.
      METHODS: Wistar and GK rats were used at 10 and 18 weeks of age. Changes in the
      ratio of intracavernosal pressure/mean arterial pressure (ICP/MAP) after
      electrical stimulation of cavernosal nerve were determined in vivo. Cavernosal
      contractility was induced by electrical field stimulation (EFS) and phenylephrine
      (PE). In addition, nonadrenergic-noncholinergic (NANC)- and sodium nitroprusside
      (SNP)-induced relaxation were determined. Cavernosal neuronal nitric oxide
      synthase (nNOS) and endothelial nitric oxide synthase (eNOS) mRNA and protein
      expression were also measured. MAIN OUTCOME MEASURE: GK diabetic rats display ED
      associated with decreased cavernosal expression of eNOS protein. RESULTS: GK rats
      at 10 and 18 weeks demonstrated impaired erectile function represented by
      decreased ICP/MAP responses. Ten-week-old GK animals displayed increased PE
      responses and no changes in EFS-induced contraction. Conversely, contractile
      responses to EFS and PE were decreased in cavernosal tissue from GK rats at 18
      weeks of age. Moreover, GK rats at 18 weeks of age displayed increased NANC
      mediated relaxation, but not to SNP. In addition, ED was associated with
      decreased eNOS protein expression at both ages. CONCLUSION: Although GK rats
      display ED, they exhibit changes in cavernosal reactivity that would facilitate
      erectile responses. These results are in contrast to those described in other
      experimental diabetes models. This may be due to compensatory mechanisms in
      cavernosal tissue to overcome restricted pre-penile arterial blood supply or
      impaired veno-occlusive mechanisms.

PMID- 20807327
TI  - A new female rat animal model for hypoactive sexual desire disorder; behavioral
      and pharmacological evidence.
AB  - INTRODUCTION: Female sexual dysfunction (FSD) affects 33-48% of women. Female
      rats with low sexual activity might model FSD. AIM: In this study, we have
      investigated whether in a population of normal female rats, subpopulations of
      rats exist with different levels of sexual behavior. METHODS: Sexually
      experienced, intact, estradiol-primed female rats were placed in an empty
      compartment adjacent to a compartment with a male. The females were allowed,
      during 30 minutes, to switch between the compartments via a hole through which
      only the females could pass (paced mating). Next, we investigated the acute
      effects on female sexual behavior of apomorphine, a D(1) - and D(2) -type
      dopamine receptor agonist, (+/-)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide
      (+/- 8-OH-DPAT), a 5-HT1A receptor agonist, and paroxetine, a selective serotonin
      reuptake inhibitor. MAIN OUTCOME MEASURES: Time spent in compartments, proceptive
      behaviors, contact-return latencies, and percentages of exits were quantified.
      RESULTS: Based on their behavior in the paced mating sex test, estradiol-primed,
      intact female rats can be divided into three groups: those that mostly avoid the
      male, a large middle group, and those that mostly approach the male. The avoiders
      also showed significantly less proceptive behavior than the male approachers. The
      sexual behavior of the females was relatively stable over time, suggesting the
      existence of different endophenotypes in female rats. Apomorphine and +/- 8-OH
      DPAT had an inhibiting effect on sexual behavior, but only females dosed with
      apomorphine showed a different response in avoiders and approachers, more
      inhibiting effect in avoiders than approachers. Paroxetine had no effect on
      proceptive behavior. DISCUSSION: The stable, male-avoiding behavior of some
      females might correspond to the characteristics of women with FSD. Therefore,
      these avoiders are a promising new model for FSD, specifically for sexual desire
      and/or arousal disorders. Furthermore, the apomorphine data suggest that
      differences in the dopamine system may (partly) underlie the differences in
      sexual behaviors between avoiders and approachers.

PMID- 20807328
TI  - The development of a sensory substitution system for the sexual rehabilitation of
      men with chronic spinal cord injury.
AB  - INTRODUCTION: Sexual health is often severely impacted after spinal cord injury
      (SCI). Current research has primarily addressed male erection and fertility, when
      in fact pleasure and orgasm are top priorities for functional recovery. Sensory
      substitution technology operates by communicating input from a lost sensory
      pathway to another intact sensory modality. It was hypothesized that through
      training and neuroplasticity, mapped tongue sensations would be interpreted as
      sensory perceptions arising from insensate genitalia, and improve the sexual
      experience. AIM: To report the development of a sensory substitution system for
      the sexual rehabilitation of men with chronic SCI. METHODS: Subjects performed
      sexual self-stimulation while using a novel sensory substitution device that
      mapped the stroking motion of the hand to a congruous flow of electrocutaneous
      sensations on the tongue. MAIN OUTCOME MEASURES: Three questionnaires, along with
      structured interviews, were used to rate the perceived sexual sensations
      following each training session. RESULTS: Subjects completed 20 sessions over
      approximately 8 weeks of training. Each subject reported an increased level of
      sexual pleasure soon after training with the device. Each subject also reported
      specific perceptions of cutaneous-like sensations below their lesion that matched
      their hand motion. Later sessions, while remaining pleasurable and interesting,
      were inconsistent, and no subject reported an orgasmic feeling during a session.
      The subjects were all interested in continuing training with the device at home,
      if possible, in the future. CONCLUSIONS: This study is the first to show that
      sensory substitution is a possible therapeutic avenue for sexual rehabilitation
      in people lacking normal genital sexual sensations. However more research, for
      instance on frequency and duration of training, is needed in order to induce
      functional lasting neuroplasticity. In the near term, SCI rehabilitation should
      more fully address sexuality and the role of neuroplasticity for promoting the
      maximal potential for sexual pleasure and orgasm.

PMID- 20807330
TI  - Treatment of 161 men with symptomatic late onset hypogonadism with long-acting
      parenteral testosterone undecanoate: effects on body composition, lipids, and
      psychosexual complaints.
AB  - INTRODUCTION: Elderly men may suffer from late-onset hypogonadism (LOH). The long
      term effects of long-acting testosterone undecanoate (TU) in a large number of
      LOH men have not yet been reported. Aims.  We analyzed the effects of
      normalization of plasma testosterone (T) in LOH men. METHODS: The records of 161
      men with LOH (baseline T<300 ng/dL) were reviewed and 100 men had used parenteral
      TU for >12 months. The mean duration of treatment was 90.6 weeks (54 to 150
      weeks). MAIN OUTCOME MEASURES: Body mass index (BMI), waist circumference,
      percentage body fat, total cholesterol, high-density lipoprotein (HDL)
      cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, prostate
      specific antigen (PSA), and hematocrit were measured. Further the Aging Male
      Symptoms' scale (AMS) and the International Index of Erectile Function (IIEF-5
      and 15) were scored. RESULTS: T therapy was associated with a significant decline
      in waist circumference (P=0.028) and percentage body fat (P<0.001), but no change
      of BMI. Total cholesterol and LDL cholesterol declined significantly (P=0.005 and
      P=0.024, respectively), with no significant changes of HDL cholesterol and
      triglycerides. The scores of sub-scales of AMS (psychological, somotovegetative
      and sexual factors) decreased (P=0.044, P=0.200 and P=0.071, respectively). The
      mean IIEF-5 (P=0.011) and IIEF-15 scores (P=0.021) improved significantly.
      Erectile function domain, orgasmic function domain, sexual desire domain,
      intercourse satisfaction domain, and overall satisfaction domain improved. Median
      PSA rose from 0.95 (0.640; 1.558) ng/mL to 1.480 (1.015; 2.275) ng/mL (P<0.001),
      with 11 patients >4 ng/mL (4.01-13.21). On biopsy there was no evidence for
      malignancy. The mean hematocrit level increased significantly from 42.3+/-3.4% to
      47.1+/-3.8%. CONCLUSIONS: Normalizing serum T in men with LOH resulted in
      improvement of the metabolic syndrome, mood and sexual functions and appeared
      acceptably safe.

PMID- 20807329
TI  - p38 Mitogen-activated protein kinase (MAPK) increases arginase activity and
      contributes to endothelial dysfunction in corpora cavernosa from angiotensin-II
      treated mice.
AB  - INTRODUCTION: Angiotensin II (AngII) activates p38 mitogen-activated protein
      kinase (MAPK) and elevates arginase activity in endothelial cells. Upregulation
      of arginase activity has been implicated in endothelial dysfunction by reducing
      nitric oxide (NO) bioavailability. However, signaling pathways activated by AngII
      in the penis are largely unknown. AIM: We hypothesized that activation of p38
      MAPK increases arginase activity and thus impairs penile vascular function in
      AngII-treated mice. METHODS: Male C57BL/6 mice were implanted with osmotic
      minipumps containing saline or AngII (42 ug/kg/h) for 14 days and cotreated with
      p38 MAPK inhibitor, SB 203580 (5 ug/kg/day), beginning 2 days before minipump
      implantation. Systolic blood pressure (SBP) was measured. Corpus cavernosum (CC)
      tissue was used for vascular functional studies and protein expression levels of
      p38 MAPK, arginase and constitutive NO synthase (NOS), and arginase activity.
      MAIN OUTCOME MEASURES: Arginase expression and activity; expression of phospho
      p38 MAPK, endothelial NOS (eNOS) and neuronal NOS proteins; endothelium-dependent
      and nitrergic nerve-mediated relaxations were determined in CC from control and
      AngII-infused mice. RESULTS: AngII increased SBP (22%) and increased CC arginase
      activity and expression (~twofold), and phosphorylated P38 MAPK levels (30%) over
      control. Treatment with SB 203580 prevented these effects. Endothelium-dependent
      NO-mediated relaxation to acetylcholine was significantly reduced by AngII and
      this effect was prevented by SB 203580 (P < 0.01). AngII (2 weeks) did not alter
      nitrergic function. However, SB 203580 significantly increased nitrergic
      relaxation in both control and AngII tissue at lower frequencies. Maximum
      contractile responses for phenylephrine and electrical field stimulation were
      increased by AngII (56% and 171%, respectively) and attenuated by SB 203580
      treatment. AngII treatment also decreased eNOS phosphorylation at Ser-1177
      compared to control. Treatment with SB 203580 prevented all these changes.
      CONCLUSION: p38 MAPK inhibition corrects penile arginase activity and protects
      against erectile dysfunction caused by AngII.

PMID- 20807331
TI  - The impact of erectile dysfunction on the quality of life of men undergoing
      hemodialysis and its association with depression.
AB  - INTRODUCTION: Erectile dysfunction (ED) is highly prevalent among men undergoing
      hemodialysis. AIM: This study was performed to identify the influence of ED on
      the patient's quality of life (QoL) and to evaluate the influence of depression
      on erectile function of these patients. MAIN OUTCOME MEASURES: For this
      multicenter cross-sectional study, 275 patients were interviewed through
      questionnaires: the five-item version of the International Index of Erectile
      Function was used for diagnosing and classifying ED; the Medical Outcomes Study
      Questionnaire 36-Item Short Form Health Survey (SF-36) for scoring QoL; and the
      Hospital Anxiety and Depression Scale (HADS) to evaluate depressive symptoms.
      Linear regression was used to examine the associations between some of the
      variables and ED. Predialytic biochemical and hematological parameters were
      determined during the longer interdialytic period. RESULTS: Patients had a mean
      age of 48.6 +/- 12.8 years, and the ED prevalence was 72.3%. Advanced age,
      diabetes and depression score were independent risk factors for the development
      of ED as confirmed by linear regression (P < 0.001, P = 0.002, and P < 0.001,
      respectively). QoL was worse among patients with any degree of ED, and the scores
      were statistically significant for overall health rating (P = 0.016), physical
      composite score (P = 0.003), bodily pain (P = 0.042), physical functioning (P <
      0.001), and vitality (P = 0.005). Furthermore, more severe forms of ED were
      associated with a lower QoL. After adjustment for some variables, such as age,
      time under dialysis, hemoglobin, albumin, parathyroid hormone, Kt/V, and
      depression, linear regression showed that domains related to poorer physical
      functioning (P = 0.047) and decreased vitality (P = 0.009) were significantly
      related to ED. CONCLUSION: Depression is an important trigger for the development
      of ED in hemodialysis patients, and this sexual condition is an independent risk
      factor for their poor QoL.

PMID- 20807332
TI  - Traditional medicine, corpus cavernosum and hydrogen sulphide.

PMID- 20807333
TI  - Testosterone and metabolic syndrome: a meta-analysis study.
AB  - INTRODUCTION: Metabolic syndrome (MetS) is often associated with male
      hypogonadism. Despite the well-known link, the role of testosterone replacement
      therapy (TRT) in MetS has not been completely clarified. AIM: To systematically
      analyse the relationship between androgen levels and MetS we performed a review
      and meta-analyses of available prospective and cross-sectional studies. In
      addition, a specific meta-analysis on the metabolic effects of TRT in available
      randomized clinical trials (RCTs) was also performed. METHODS: An extensive
      Medline search was performed including the following words
      "testosterone,""metabolic syndrome," and "males". MAIN OUTCOME MEASURES: Out of
      323 retrieved articles, 302 articles were excluded for different reasons. Among
      the 20 published studies included, 13, 3, and 4 were cross-sectional,
      longitudinal, and RCTs, respectively. Another unpublished RCT was retrieved on
      http://www.clinicaltrials.gov. RESULTS: MetS patients showed significantly lower
      T plasma levels, as compared with healthy individuals. Similar results were
      obtained when MetS subjects with and without erectile dysfunction were analyzed
      separately or when NCEP-ATPIII MetS criteria were compared with other
      definitions. Meta-regression analysis demonstrated that type 2 diabetes (T2DM)
      increased the MetS-associated T fall. In a multiple regression model, after
      adjusting for age and BMI, both T2DM and MetS independently predicted low
      testosterone (adj. r = -0.752; P < 0.001 and -0.271; P < 0.05, respectively).
      Analysis of longitudinal studies demonstrated that baseline testosterone was
      significantly lower among patients with incident MetS in comparison with controls
      (2.17 [-2.41;-1.94] nmol/L; P < 0.0001). Combining the results of RCTs, TRT was
      associated with a significant reduction of fasting plasma glucose, homeostatic
      model assessment index, triglycerides, and waist circumference. In addition, an
      increase of high-density lipoprotein cholesterol was also observed. CONCLUSIONS:
      The meta-analysis of the available cross-sectional data suggests that MetS can be
      considered an independent association of male hypogonadism. Although only few
      RCTs have been reported, TRT seems to improve metabolic control, as well as
      central obesity.

PMID- 20807334
TI  - Poly(ADP-Ribose) polymerase inhibition improves erectile function in diabetic
      rats.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a common and hard-to-treat
      complication of diabetes mellitus (DM). Multiple lines of evidence have shown
      that poly(ADP-ribose) polymerase (PARP) activation plays an important role in
      neurovascular dysfunction in diabetes, which is the crucial mechanism for
      diabetic ED. AIM: To investigate the preventive benefit of a PARP inhibitor in a
      rat model of ED induced by diabetes. METHODS:   Established streptozotocin
      diabetic male Sprague-Dawley rats were given PJ-34, a selective PARP inhibitor,
      by oral gavage at a dose of 10 mg/kg twice daily for 8 weeks. Erectile responses
      under electrical stimulation of the cavernous nerve, PARP activity and reactive
      oxygen species (ROS) production were measured. Nitric oxide synthase (NOS)
      isoforms were evaluated by Western blot and real-time quantitative PCR. Nuclear
      factor-kappa B activition and apoptosis in corpus cavernosa (CC) were also
      investigated. MAIN OUTCOME MEASURES: The effects of PARP inhibition on the
      development of diabetic ED were determined. RESULTS: Diabetes markedly attenuated
      the erectile responses (intracavernosal pressure/mean systemic arterial blood
      pressure) and these were partially prevented by PJ-34 treatment. Promoted
      oxidative stress associated PARP activation was found in CC from vehicle-treated
      diabetic rats. PJ-34 blocked PARP activity and the diabetes-associated ROS
      generation. Decreased expression and activity of constitutive NOS (cNOS),
      including endothelial NOS (eNOS) and neuronal NOS (nNOS), associated with
      enhanced inducible NOS (iNOS) expression and activity were observed in vehicle
      treated diabetic rats. Although PJ-34 had no effect on eNOS expression, it
      significantly prevented the decrease in nNOS expression and cNOS activity, and
      inhibited iNOS expression and activity in diabetic rats. PARP blockade by PJ-34
      to some extent prevented diabetes-associated apoptosis and NF-kappaB activation.
      CONCLUSIONS: Our results indicate that PARP activation plays an important role in
      the pathogenesis of diabetic ED and PARP inhibition may be a promising strategy
      to prevent development of diabetic ED.

PMID- 20807335
TI  - Occurrence of Vibrio vulnificus in mussel farms from the Varano lagoon
      environment.
AB  - AIMS: Monitoring the occurrence of the human pathogen Vibrio vulnificus in a
      mussel farm located in the lagoon of Varano (Italy). METHODS AND RESULTS: A total
      of 72 samples of mussel, water and sediment, collected from two locations of
      Varano lagoon in the Gargano peninsula, during a 7-month survey, were analysed.
      Isolation and PCR characterization of six V. vulnificus environmental genotype
      strains revealed that this pathogen was isolated when with T was above 22 
      degrees C and salinity ranged between 22.7 and 26.40/00. No significant
      correlation of the occurrence of V. vulnificus with water pH or salinity was
      observed. Moreover, 8% of mussel samples were found to be contaminated by V.
      vulnificus. All of that positive mussel samples originated from the same sampling
      station. CONCLUSION: It is suggested that warmer season are risky to eat raw or
      undercooked bivalve molluscs in the local area. SIGNIFICANCE AND IMPACT OF THE
      STUDY: To increase knowledge about environmental conditions that may affect the
      occurrence of waterborne pathogen Vibrio vulnificus in seafood.

PMID- 20807336
TI  - Prevalence, risk factors and causes of discordance in fibrosis staging by
      transient elastography and liver biopsy.
AB  - BACKGROUND AND AIMS: Liver stiffness measurement (LSM) by transient elastography
      (TE) is widely used for the noninvasive assessment of fibrosis. Our objectives
      were to examine the prevalence, risk factors and causes of discordance between
      fibrosis estimated by TE and liver biopsy. METHODS: Two hundred and fifty-one
      patients with hepatitis B, C and nonalcoholic fatty liver disease underwent LSM
      by TE and liver biopsy. Predictors of discordance (>=2 fibrosis stages) between
      measures, which occurred in 14% of patients (n=35), were identified by comparing
      patient, TE and biopsy characteristics of discordant and nondiscordant cases.
      RESULTS: According to predefined criteria, 40% of discordances were attributed to
      TE error and 23% to biopsy error; 37% were indeterminate. In multivariate
      analysis, mild fibrosis (F0-2 vs. F3-4), and higher body mass index (BMI), ALT
      and LSM variability [assessed by the ratio of the interquartile range to median
      LSM (IQR/M)] were independently associated with discordance. Discordance was
      three-fold more common in patients with obesity (28 vs. 9%), ALT >=60 U/L (20 vs.
      7%) and IQR/M >=0.17 (22 vs. 7%; all P<0.005). Based on these variables, a
      discordance risk score assigning 1 point to each factor was developed. The
      prevalence of discordance in patients with 0, 1, 2 and 3 factors were 2, 7, 20,
      and 55% respectively (P<0.0005). CONCLUSIONS: Discordance between liver fibrosis
      estimated by TE and biopsy occurs in one in seven patients. In assessing the
      validity of TE results, clinicians must recognize risk factors for discordance
      and in at-risk patients, consider alternative measures including biomarkers and
      possibly biopsy.

PMID- 20807337
TI  - Hybridization and introgression across different ploidy levels in the Neotropical
      orchids Epidendrum fulgens and E. puniceoluteum (Orchidaceae).
AB  - The hypothesis of gene flow between species with large differences in chromosome
      numbers has rarely been tested in the wild, mainly because species of different
      ploidy are commonly assumed to be reproductively isolated from each other because
      of instantaneous and strong postzygotic barriers. In this study, a broad-scale
      survey of molecular variation was carried out between two orchid species with
      different ploidy levels: Epidendrum fulgens (2n = 2x = 24 chromosomes) and
      Epidendrum puniceoluteum (2n = 4x = 52 chromosomes). To test the strength of
      their reproductive barriers, we investigated the distribution of genetic
      variation in sympatric and allopatric populations of these two species and
      conducted crossing experiments. Nuclear and plastid microsatellite loci were used
      to genotype 463 individuals from eight populations across the geographical range
      of both species along the Brazilian coastal plain. All six sympatric populations
      analysed presented hybrid zones, indicating that hybridization between E. fulgens
      and E. puniceoluteum is a common phenomenon. Bayesian assignment analysis
      detected the presence of F(1) and F(2) individuals and also signs of
      introgression, demonstrating a high potential for interspecific gene flow.
      Introgression occurs preferentially from E. fulgens to E. puniceoluteum. Pure
      parental individuals of both species display strong genotype-habitat
      associations, indicating that environment-dependent selection could be acting in
      all hybrid zones. This study suggests that hybridization and introgression are
      evolutionary processes playing a role in the diversification of Epidendrum and
      indicates the importance of investigations of hybrid zones in understanding
      reproductive barriers and speciation processes in Neotropical orchid species.

PMID- 20807338
TI  - Myo-inositol abolishes salicylic acid-dependent cell death and pathogen defence
      responses triggered by peroxisomal hydrogen peroxide.
AB  - * Signalling between reactive oxygen species (ROS) and salicylic acid (SA)
      dependent programmed cell death (PCD) and defence responses is complex and much
      remains to be discovered. Recent reports have implicated myo-inositol (MI) in
      defence responses, but the relationships between MI, ROS and SA remain to be
      elucidated. * This question was investigated in catalase-deficient Arabidopsis
      thaliana plants (cat2), in which a peroxisomal H(2) O(2) trigger induces SA
      dependent lesion formation and a wide range of pathogen responses. * GC-MS
      analysis revealed that leaf MI contents were markedly decreased in cat2
      independently of SA accumulation. Supplying MI to cat2 blocked lesion formation,
      SA accumulation and associated defence responses in a manner that closely
      mimicked the effect of genetically blocking SA synthesis through isochorismate
      synthase 1 (ICS1). The effects of MI were linked to repression of ICS1
      transcripts but not decreased oxidative stress or signalling, and caused loss of
      resistance to virulent bacteria. The antagonistic effects of MI on lesion
      formation and resistance could be partly restored by supplying SA. * Our findings
      demonstrate a role for MI in cell death triggered by peroxisomal H(2) O(2) , and
      suggest that the tissue content of this compound is a key factor determining
      whether oxidative stress induces or opposes defence responses.

PMID- 20807339
TI  - Contrasting impacts of climate-driven flowering phenology on changes in alien and
      native plant species distributions.
AB  - * Plant phenology is particularly sensitive to climate and a key indicator of
      environmental change. Globally, first flowering dates (FFDs) have advanced by
      several days per decade in response to recent climate warming, but, while earlier
      flowering should allow plant distributions to increase, a link between FFD and
      range changes has not been observed. * Here I show for 347 species that the
      extent to which FFD has responded to climate warming is linked to the degree to
      which their relative distributions have changed over 30 yr across the British
      Isles. * Native plant species whose phenology did not track climate change
      declined in distribution, whereas species that became more widespread all
      exhibited earlier flowering. In contrast, alien neophytes showed both a stronger
      phenological response to warming and a more marked increase in distribution, but
      no link between the two. * These trends were consistent both for relative changes
      in the national distribution and for local abundance. At the national scale, the
      more recently an alien species became established in Britain, the more likely it
      was to increase in distribution irrespective of FFD, suggesting that recent
      changes in alien species distributions are decoupled from climate and driven by
      other factors.

PMID- 20807340
TI  - Direct selection at the blossom level on floral reward by pollinators in a
      natural population of Dalechampia schottii: full-disclosure honesty?
AB  - * Both floral rewards and advertisements can be important in the attraction of
      pollinators, but few studies have separated the individual contributions of
      rewards and advertisements to fitness. * Here, we investigated selection by
      pollinators on individual blossoms in Dalechampia schottii. This Neotropical
      vine, endemic to the Yucatan Peninsula, rewards bees by secreting fully visible,
      deep-blue resin from a gland subtended by two conspicuous petaloid bracts that
      may play the role of advertisement. * We used contextual analysis to build a
      fitness function for four morphological traits of individual blossoms: the amount
      of the reward as measured by gland area; the size of the advertisement trait as
      measured by bract length; the flower-pollinator fit as measured by the shortest
      distance between reward and stigma; and the potential for self-pollination as
      measured by the shortest distance between anthers and stigma. * Larger gland area
      and increased potential for self-pollination directly increased the seed
      production of individual blossoms. However, bract size or flower-pollinator fit
      did not influence the number of seeds produced by blossoms. Therefore, in this
      Dalechampia species, pollinators seem to select directly on the reward of
      individual blossoms but not on the advertising bracts.

PMID- 20807341
TI  - Inadvertent intradiscal contrast flow during lumbar transforaminal epidural
      steroid injections: a case series examining the prevalence of intradiscal
      injection as well as potential associated factors and adverse events.
AB  - OBJECTIVES: The primary aim was to evaluate the prevalence of inadvertent
      intradiscal injection during fluoroscopically guided contrast-enhanced lumbar
      transforaminal epidural steroid injections. The secondary aim was to determine if
      there are any risk factors for or adverse events as a result of inadvertent
      intradiscal contrast injection. DESIGN: The study was a retrospective case
      series. SETTING: The study was set in three outpatient spine care centers.
      PATIENTS: A search was conducted in a database of spinal injection procedures
      from July 2000-May 2008. Fifteen cases of inadvertent intradiscal contrast flow
      were identified. These cases were matched with one control case with the same
      age, gender, level, and side of injection. INTERVENTIONS: The prevalence of
      intradiscal contrast flow with lumbar transforaminal epidural steroid injection
      was calculated. Chart review of the cases and controls was performed. An
      independent, blinded examiner evaluated needle tip placement. OUTCOME MEASURES:
      Frequency of intradiscal contrast flow during lumbar transforaminal epidural
      steroid injections and the relationship between the occurrence of intradiscal
      contrast flow with potential risk factors. RESULTS: The prevalence of inadvertent
      intradiscal injection during lumbar transforaminal epidural steroid injections
      was 0.17%. All of the patients received prophylactic antibiotics after
      inadvertent disk injection, and there were no infectious or other complications
      identified. CONCLUSIONS: Intradiscal contrast injection is an infrequently
      reported event during lumbar transforaminal epidural steroid injections. Our data
      support that the prevalence is very low and there might be an association with
      ipsilateral foraminal stenosis. Although there is potential for significant
      adverse complications with intradiscal injection, our data set did not show
      serious sequelae.

PMID- 20807342
TI  - Radiofrequency neurotomy for the treatment of therapy-resistant neck pain after
      ventral cervical operations.
AB  - OBJECTIVE: The objective of this study was to determine if radiofrequency
      neurotomy is effective for patients with postoperative neck pain after cervical
      spine operations. DESIGN: The study design used was a retrospective practice
      audit. SETTING: Review of charts of all patients who underwent cervical spine
      operations for degenerative reasons during a time period of 2.5 years.
      INTERVENTIONS: Patients with persistent postsurgical neck pain were treated with
      therapeutic medial branch blocks (local anesthetic and steroid). If pain
      recurred, diagnostic medial branch blocks were performed. Patients with at least
      80% relief following both the therapeutic and the diagnostic block underwent
      radiofrequency neurotomy. Positive treatment response was defined for at least
      50% reduction of pain or sufficiently satisfaction of the patient. RESULTS: Two
      hundred forty-two operations were performed, 125 of which were artificial disc
      operations, 66 were stand alone cages, and 51 were fusions with cage and plate.
      Two patients were lost to follow-up. Persistent neck pain occurred in 31% of the
      patients. The prevalence of zygapophysial pain after surgery was 13.2%. These 32
      patients were treated with radiofrequency neurotomy because of recurrent neck
      pain. The average follow-up time was 15 months. A significant pain reduction was
      achieved in 59.4%. Significantly, after a double-level operation, more patients
      suffered persisting neck pain (P=0.002) compared with all patients being
      operated. CONCLUSIONS: Zygapophysial joints are a possible source of
      postoperative pain after anterior cervical spine surgery. Persistent and therapy
      resistant neck pain occurs more often in patients after double-level operation.
      Radiofrequency neurotomy can provide an effective treatment for persistent neck
      pain after ventral cervical spine surgery.

PMID- 20807343
TI  - Comparison of the effectiveness of lumbar transforaminal epidural injection with
      particulate and nonparticulate corticosteroids in lumbar radiating pain.
AB  - OBJECTIVE: Lumbar transforaminal epidural steroid injections are procedures often
      utilized in the treatment of low back pain associated with radicular pain.
      Particulate steroids have been known to play a role in embolism. It is, unknown
      whether nonparticulate steroids are as effective as particulate steroids. To
      investigate the effect of an epidural steroid injection on back pain, we
      conducted a randomized, controlled trial comparing nonparticulate steroid with
      particulate steroid to treat lumbar disc herniation. DESIGN: One hundred-six
      patients were randomized to receive lumbar transforaminal epidural steroid
      injections (N = 53) with either dexamethasone 7.5 mg, or with triamcinolone
      acetate 40 mg (N = 53). Measurement were taken before treatment and one month
      after treatment using a visual analog scale, short McGill pain questionnaire, and
      revised Oswertry Back Disability Index. RESULTS: There was a statistically
      significant difference in the visual analog score between those treated with
      dexamethasone and those given triamcinolone. The two groups did not differ
      significantly on the McGill Pain Questionnaire, or the Oswestry Disability Index
      before and after treatment. CONCLUSION: In this study, dexamethasone and
      triamcinolone treatments were shown to have different effects on low back pain
      with sciatica, with triamcinolone being more effective than dexamethsone in
      lumbar radiculopathy.

PMID- 20807344
TI  - Associations between heat pain perception and pain severity among patients with
      chronic pain.
AB  - OBJECTIVE: The primary aim of this study was to investigate the associations
      between standardized values of thermal sensory perception and standardized scores
      of clinical pain among a heterogeneous cohort of adults with chronic pain that
      included individuals receiving chronic opioid therapy. DESIGN: The study used a
      prospective design. SETTING: The study was set in a multidisciplinary pain
      rehabilitation center at a tertiary medical center. PATIENTS: The cohort included
      163 patients (female 58%) who met inclusion criteria, and were admitted from
      March 2007 to June 2008. INTERVENTION: Using a validated quantitative sensory
      test method of levels, standardized values of heat pain (HP) perception and
      cooling detection threshold were obtained 1day following admission. OUTCOME
      MEASURES: Standardized scores of clinical pain were obtained at admission using
      the pain severity subscale of the Multidimensional Pain Inventory. RESULTS: At
      admission, 109 (67%) patients were using opioids, and the mean morphine
      equivalent dose was 192mg/day. The mean pain duration was 10.5years, and the two
      most frequent diagnoses were low back pain (29%) and headache (12%). A
      significant negative correlation was found between pain severity and HP threshold
      (r=-0.170, P=0.030), where lower values of HP threshold correlated with greater
      scores of pain severity. Post hoc linear regression analysis showed the
      association between HP threshold and pain severity retained statistical
      significance (P=0.039) after adjusting for opioid dose, pain duration and pain
      diagnosis. CONCLUSION: The use of standardized values of HP perception and
      clinical pain may be key methodological approaches for investigating the clinical
      correlates of HP perception among heterogeneous populations of adults with
      chronic pain.

PMID- 20807345
TI  - A novel 12-week study, with three randomized, double-blind placebo-controlled
      periods to evaluate fentanyl buccal tablets for the relief of breakthrough pain
      in opioid-tolerant patients with noncancer-related chronic pain.
AB  - OBJECTIVE: To evaluate the time of onset, overall efficacy, and safety of
      fentanyl buccal tablet (FBT) for noncancer-related breakthrough pain (BTP) in
      opioid-tolerant adults over 12 weeks. DESIGN: A novel 12-week study that mimicked
      clinical practice with dose titration to effective dose, open-label treatment,
      and three randomized, double-blind, placebo-controlled, multiple-crossover
      periods at weeks 4, 8, and 12. For each double-blind period, study patients
      received nine doses (FBT = 6, placebo = 3) in a randomized sequence. SETTING:
      Twenty-one study centers in the United States. POPULATION: Opioid-tolerant adults
      with noncancer-related chronic pain and BTP. OUTCOME MEASURES: The primary
      outcome was the sum of the pain intensity differences (PID) 5-60 minutes post
      dose (SPID60) during the final double-blind period. Secondary outcomes included
      pain relief (PR), meaningful PR, and proportion of episodes with a PID of >=33%
      and >=50%. RESULTS: Of 148 patients who entered the titration phase, 105 (71%)
      achieved a successful dose and 81 (55%) participated in all three assessment
      periods in the study. The final RCT assessment period results demonstrated
      continued efficacy of FBT vs placebo (P < 0.05) for SPID60 (mean [SD]: 7.7 [6.2]
      vs 4.6 [4.7]). The average onset of PR began at 5 minutes, with meaningful PR by
      <=10 minutes. The proportion of episodes with >=33% improvement in PI was 7% with
      FBT vs 3% with placebo at 5 minutes and with >=50% was 17% vs 10% at 15 minutes.
      All periods showed similar results. Adverse events and patient discontinuations
      were generally typical of clinical opioid use. CONCLUSIONS: FBT showed continued
      clinically important analgesic effects and was generally well tolerated over 12
      weeks of treatment.

PMID- 20807346
TI  - Medical malpractice allegations of iatrogenic addiction in chronic opioid
      analgesic therapy: forensic case reports.
AB  - OBJECTIVES: The objectives for presenting these medico-legal forensic case
      reports are the following: 1) detail three cases where chronic opioid analgesic
      therapy (COAT) was alleged to cause iatrogenic addiction and/or re-addiction; 2)
      detail the plaintiff's and defendant's medical experts' opinions on these
      allegations; and 3) through analyzing these cases, develop some recommendations
      for future prevention of such allegations during COAT. METHODS: Case Reports.
      RESULTS: Medico-legal issues surrounding the allegation of iatrogenic addiction
      were identified in each case. CONCLUSIONS: Before starting COAT, physicians
      should obtain and document patient informed consent for the risk of addiction/re
      addiction with COAT treatment. Patients with a history of addictions pre-COAT
      should be placed on adherence monitoring immediately on beginning COAT.

PMID- 20807347
TI  - Factors associated with clinician intention to address diverse aspects of pain in
      seriously ill outpatients.
AB  - BACKGROUND: Pain is a common, often undertreated problem among patients with
      palliative needs. OBJECTIVES: To evaluate clinician factors associated with
      intention to address diverse aspects of pain. DESIGN: Clinicians reviewed a
      clinical vignette describing a frail elderly patient with advanced hormone
      refractory metastatic prostate cancer, depression, and pain not on analgesic
      therapy. Clinicians were surveyed about their intentions for treatment.
      PARTICIPANTS: All 280 primary care and specialist clinicians working in 19
      hospital and community-based primary care, oncology, and cardiology clinics at
      eight geographically dispersed sites in two large VA hospital systems. MAIN
      MEASURES: Endpoints were clinician intention to deliver guideline-concordant
      care: prescribe opioids/antidepressants, assess existential wellbeing, and offer
      mental health referral. Demographic and behavioral measures were evaluated in
      association with endpoints. KEY RESULTS: Of 208 (74%) responding practitioners,
      189 were responsible for prescribing decisions. Of those, 86, 77, 75, and 69 were
      "very"/"somewhat likely" to prescribe opioids, antidepressants, refer to a mental
      health specialist, or assess existential wellbeing, respectively. Factors
      associated with greater intent to prescribe an opioid or antidepressant included
      female gender, being an attending physician, being a primary care clinician, and
      greater confidence in pain management skills. Greater trust in the validity of
      pain ratings was associated with intent to prescribe an antidepressant and assess
      existential wellbeing. Prescribing opioids was less likely if perceived as an
      administrative burden. Assessing existential wellbeing was less likely if time
      constraints were perceived a barrier to evaluating pain. Female gender was the
      only factor associated with intent to refer to a mental health specialist.
      CONCLUSIONS: Our findings suggest useful targets for improving pain management
      include bolstering clinician confidence in pain management and their trust in
      pain ratings.

PMID- 20807348
TI  - Evidence-based manual therapy for chronic musculoskeletal pain: the challenges.

PMID- 20807349
TI  - Fentanyl buccal tablet for breakthrough cancer pain: why titrate?
AB  - Breakthrough cancer pain is a significant problem for many patients with cancer
      because of the fast onset and often unpredictable nature of the pain episodes.
      The rapid onset opioids therefore have a central role to play in the management
      of breakthrough cancer pain. The rapid onset opioid fentanyl buccal tablet
      provides a fast analgesic effect and is easy to administer. However, titration of
      the medication is essential in order to optimize the management of pain. This is
      because individual patient characteristics, comorbidities, and other treatments
      may influence the absorption, pharmacokinetics, and pharmacodynamics of drugs. It
      is therefore important to individualize treatment by determining the effective
      dose for each patient, which is the dose that provides adequate analgesia and
      minimizes undesirable adverse effects. Data from clinical studies of fentanyl
      buccal tablet show that patients' effective doses ranged from 100 to 800 ug per
      episode, highlighting the need for the titration process. Following successful
      dose titration, treatment with fentanyl buccal tablet can achieve significant
      pain relief as early as 10 minutes after administration, resulting in a high
      level of patient satisfaction.

PMID- 20807350
TI  - Prevalence of exposure to potential CYP450 pharmacokinetic drug-drug interactions
      among patients with chronic low back pain taking opioids.
AB  - Drug-drug interactions (DDIs) have been defined as two or more drugs interacting
      in such a way that the effectiveness and/or toxicity of one or all drugs are
      changed. Patients taking more than one drug metabolized through the cytochrome
      P450 (CYP450) enzyme system, including some, but not all, opioids experience a
      drug-drug exposure (DDE), which may result in a potentially dangerous DDI. Using
      a retrospective analysis of a large commercial claims database and a Medicare
      database, we evaluated DDEs that have the potential to cause DDIs among chronic
      low back pain (cLBP) patients on long-term opioid analgesia, which metabolizes
      through the CYP450 enzyme system, concomitant with other CYP450-metabolized
      drug(s). The overall prevalence of DDEs among cLBP patients was 27%. Women had a
      higher prevalence of DDEs (30.6% vs. 22% for men). Patients aged 45 to 55 and 56
      to 64 years had the highest prevalence of DDEs (30.4% and 29.8%, respectively),
      followed by patients 34 to 45 years (27.9%). For patients>65 years, the
      prevalence of DDEs was 23.1%. In general, the prevalence of DDEs was fairly
      consistent across age ranges in this population. This study suggests that DDEs
      are common in the cLBP population. When selecting an opioid to treat cLBP,
      physicians should consider the potential for exposure of these patients to drugs
      that might unfavorably interact and, for that reason, the use of opioids that do
      not rely on the CYP450 system as their primary means of metabolism might be
      worthy of consideration.

PMID- 20807351
TI  - Comparison of medication adherence and healthcare costs between duloxetine and
      pregabalin initiators among patients with fibromyalgia.
AB  - OBJECTIVE: To examine and compare medication adherence and direct healthcare
      costs between duloxetine and pregabalin initiators among patients with
      fibromyalgia. METHODS: A retrospective analysis of commercially insured
      fibromyalgia patients aged 18 to 64 was conducted among those who initiated
      duloxetine or pregabalin between January 1, 2006 and December 31, 2006. The first
      initiation date was defined as the index date. All patients included had
      continuous enrollment in the 12-month pre- and post-index periods. Each
      individual was classified in the duloxetine or pregabalin cohort based on the
      initiating agent. The pregabalin cohort was constructed via propensity scoring
      controlling for differences in demographics, pre-index clinical and economic
      characteristics, and pre-index treatment patterns. Medication adherence (ie,
      medication possession ratio [MPR] and proportion of patients with MPR>=80%) and
      healthcare costs over the 12 months post-index period were examined between
      cohorts. RESULTS: The study cohorts included 3,711 duloxetine and 4,111
      pregabalin patients with the mean age of 51 years. The common comorbidities
      included neuropathic pain other than diabetic peripheral neuropathic pain, low
      back pain, cardiovascular disease, headache, and osteoarthritis. Over 80% of the
      duloxetine or pregabalin initiators used opioids. Controlling for demographics,
      pre-index clinical and economic characteristics, and prior medication history,
      duloxetine patients had significantly higher MPR (0.7 vs. 0.5, P<0.05), higher
      proportion of patients with MPR>=80% (46.5% vs. 26.4%, P<0.05), but significantly
      lower total healthcare costs ($19,378 vs. $27,045, P<0.05) over the 12 months
      post-index period than pregabalin patients. CONCLUSION: Fibromyalgia patients on
      duloxetine had significantly higher medication adherence, but significantly lower
      direct healthcare costs than those on pregabalin.

PMID- 20807352
TI  - Technical and imaging report: fluoroscopic guidance for diagnosis and treatment
      of lumbar synovial cyst.
AB  - Lumbar synovial cysts can be a source of low back pain with or without
      radiculopathy depending upon the size and location of the mass. Options for
      treatment range from analgesics to surgery, depending upon the degree of nerve
      root or spinal cord impingement. Attempts at minimally invasive treatment such as
      computed tomography-assisted aspiration and cyst rupture are documented in the
      radiology literature with varying degrees of reported success. This case report
      is the first to document the fluoroscopically-guided management of a lumbar
      synovial cyst in the pain medicine literature and highlights the knowledge and
      technical skills required when treating such cases.

PMID- 20807353
TI  - Evidence-based interventional pain medicine according to clinical diagnoses. 16.
      Complex regional pain syndrome.
AB  - Complex regional pain syndrome (CRPS), formerly known as reflex sympathetic
      dystrophy is a pain syndrome with an unclear pathophysiology and unpredictable
      clinical course. The disease is often therapy resistant, the natural course not
      always favorable. The diagnosis of CRPS is based on signs and symptoms derived
      from medical history and physical examination. Pharmacological pain management
      and physical rehabilitation of limb function are the main pillars of therapy and
      should be started as early as possible. If, however, there is no improvement of
      limb function and persistent severe pain, interventional pain management
      techniques may be considered. Intravenous regional blocks with guanethidine did
      not prove superior to placebo but frequent side effects occurred.Therefore this
      technique receives a negative recommendation (2 A-). Sympathetic block is the
      interventional treatment of first choice and has a 2 B+ rating. Ganglion
      stellatum (stellate ganglion) block with repeated local anesthetic injections or
      by radiofrequency denervation after positive diagnostic block is documented in
      prospective and retrospective trials in patients suffering from upper limb CRPS.
      Lumbar sympathetic blocks can be performed with repeated local anesthetic
      injections. For a more prolonged lumbar sympathetic block radiofrequency
      treatment is preferred over phenol neurolysis because effects are comparable
      whereas the risk for side effects is lower (2 B+). For patients suffering from
      CRPS refractory to conventional treatment and sympathetic blocks, plexus
      brachialis block or continuous epidural infusion analgesia coupled with exercise
      therapy may be tried (2 C+). Spinal cord stimulation is recommended if other
      treatments fail to improve pain and dysfunction (2 B+). Alternatively peripheral
      nerve stimulation can be considered, preferentially in study conditions (2 C+).

PMID- 20807354
TI  - Successful treatment of lichen spinulosus with topical tacalcitol cream.
AB  - Lichen spinulosus (LS) is a rare idiopathic cutaneous eruption characterized by
      follicular keratotic spiny papules that are grouped in large patches. Here, we
      report two cases of LS in the submental area, an uncommon site, which were
      treated effectively and safely with topical tacalcitol cream.

PMID- 20807355
TI  - Bullous pemphigoid in late childhood successfully treated with mycophenolate
      mofetil as an adjuvant therapy.
AB  - Bullous pemphigoid is an acquired subepidermal vesiculobullous disease most
      commonly seen in the elderly. We report a 16-year-old girl with bullous
      pemphigoid who achieved disease remission with mycophenolate mofetil as an
      adjuvant therapy.

PMID- 20807356
TI  - A diagnostic challenge: a case of acrodermatitis enteropathica without
      hypozincemia and with maternal milk of low zinc level.
AB  - Acrodermatitis enteropathica is a rare and distinct form of zinc deficiency with
      a requirement of life-long zinc supplementation and inherited in a recessive
      manner. Transient nutritional zinc deficiency is also a well known condition
      mimicking acrodermatitis enteropathica like skin changes in preterm and term
      infants who are generally breastfed with a low level of zinc containing milk.
      Here, a 4-month-old male, term and fully breastfed acrodermatitis enteropathica
      case without hypozincemia and with maternal milk of low zinc level is presented.

PMID- 20807357
TI  - A case of extensive aplasia cutis congenita: a conservative approach.
AB  - Aplasia cutis congenita is a rare, sporadic congenital malformation characterized
      by skin defects, sometimes extending to the underlying bone. We report a case of
      a boy born with a large rhomboid scalp and skull defect measuring 8 * 12 cm with
      no other anomalies. Conservative treatment led to the complete epithelization of
      the skin defect with secondary closure of the cranial vault without need for
      surgical intervention.

PMID- 20807358
TI  - A partially regressed, atrophic plaque on a 17-year-old girl: an unusual
      presentation of myofibromatosis.
AB  - Solitary cutaneous myofibromas have been reported in patients of all ages.
      Infantile and adult forms are distinguished by age of onset, location of lesions,
      and the potential for infantile myofibromas to regress. We report a case of a 17
      year-old girl with a solitary myofibroma on the right leg that presented as a
      partially regressed, atrophic plaque with multiple surrounding papules. Unusual
      features of this case include the tumor size, simultaneous regression and
      proliferation, patient age, and gender.

PMID- 20807359
TI  - Diagnosis of pilomatricoma using an otoscope.
AB  - Pilomatricoma is a benign tumor that presents as a 3-30-mm, firm, solitary, deep,
      dermal or subcutaneous tumor on the head, neck, or upper extremities. The
      clinical diagnosis is often made by the firm, sometimes rock-hard texture of the
      skin. The diagnosis can be confirmed by a skin biopsy or excision of the lesion.
      We have recently noted that pilomatricomas appear as a black mass in the skin
      when the lesion is transilluminated by placing the light of a fiberoptic otoscope
      adjacent to the skin lesion. To our knowledge, this is the first report
      demonstrating preoperative diagnosis of pilomatricoma by transilluminating the
      lesion with an otoscope.

PMID- 20807360
TI  - Fibromatosis colli with hypertrichosis: a rare case of cutaneous manifestation of
      a muscular disorder.
AB  - We describe the clinicopathologic features of an unusual case of fibromatosis
      colli. The lesion was rock hard, lateral, tightly affixed to the clavicle, and
      with overlying hypertrichosis.

PMID- 20807361
TI  - Neonatal cellulitis and sepsis caused by group A streptococcus.
AB  - We report a case of late onset neonatal invasive group A streptococcal disease
      characterized with rapidly progressing cellulitis and development of sepsis. The
      infection was acquired from benign and mild skin infection of the child's mother.
      The causative agent was group A streptococcus, belonging to the emm type 53.2,
      which usually causes mild skin disease.

PMID- 20807362
TI  - Incontinentia pigmenti in a male infant with Klinefelter syndrome: a case report
      and review of the literature.
AB  - Incontinentia pigmenti, also known as Bloch-Sulzberger syndrome, is a hereditary,
      X-linked dominant disorder characterized by abnormalities of skin, hair, teeth,
      eyes, and the central nervous system. It is classically considered a male-lethal
      disorder leading to recurrent miscarriages of male fetuses. We report a rare case
      of a surviving baby boy with the classic clinical features of incontinentia
      pigmenti that can be explained by Klinefelter syndrome.

PMID- 20807363
TI  - Leukocyte adhesion deficiency type 1 presenting with recurrent pyoderma
      gangrenosum and flaccid scarring.
AB  - We report an 11-year-old boy with a longstanding history of recurrent pyoderma
      gangrenosum and abnormal wound healing who eventually developed a fatal invasive
      fungal infection. This article emphasizes the importance to consider leukocyte
      adhesion deficiency type 1 in the differential diagnosis of patients with
      recurrent skin ulcers.

PMID- 20807364
TI  - Congenital yellow nail syndrome: a case report and its relationship to nonimmune
      fetal hydrops.
AB  - Yellow nail syndrome (YNS) is an uncommon disorder characterized by a triad of
      nail dystrophy, lymphedema, and pleural effusion. It is rare in children and
      congenital occurrence of YNS has been very rarely described. We report a 2-year
      old Arab boy having congenital yellow nail syndrome with mild facial dysmorphism
      and bilateral conjunctival pigmentation born to consanguineous parents. One of
      his older siblings had died of nonimmune fetal hydrops (NIFH). The case supports
      the genetic basis of yellow nail syndrome with a possible relationship to
      nonimmune fetal hydrops.

PMID- 20807365
TI  - Pemphigus herpetiformis in childhood.
AB  - Pemphigus herpetiformis (PH) is a rare pemphigus variant. The clinical features
      of this form of pemphigus resembles dermatitis herpetiformis, however,
      histological examination and immunofluorescence yield findings diagnostic for
      pemphigus. A 5-year-old female patient with clinical features suggestive of
      dermatitis herpetiformis is reported. Histopathological exam showed skin with
      subcorneous blisters, epidermal spongiosis containing predominantly neutrophils,
      few eosinophils and rare acantholytic cells. Direct immunofluorescence showed
      intercellular deposits of IgG and C3. The skin lesions responded poorly to
      dapsone associated with systemic corticosteroid therapy. A complete remission of
      bullous lesions was obtained with azathioprine and immunosuppressive doses of
      systemic corticosteroids (prednisone). A case of PH in childhood is reported
      here, emphasizing the rarity and young age of onset.

PMID- 20807366
TI  - Acquired partial lipodystrophy with C3 hypocomplementemia and antiphospholipid
      and anticardiolipin antibodies.
AB  - Acquired partial lipodystrophy is an extremely rare condition of unknown etiology
      characterized by progressive loss of fat of the face, neck, trunk, and upper
      extremities. It usually begins during childhood and is more common in girls. C(3)
      hypocomplementemia is seen in 70% of patients with acquired partial
      lipodystrophy. Unlike generalized forms of the disease, no insulin resistance
      occurs. We present three boys with acquired partial lipodystrophy having C(3)
      hypocomplementemia. In addition, one of them had antiphospholipid and
      anticardiolipin antibodies.

PMID- 20807367
TI  - Systemic contact dermatitis in children: how an avoidance diet can make a
      difference.
AB  - Systemic contact dermatitis is an under-recognized skin reaction that occurs
      secondary to systemic (oral, intravenous, intramuscular, inhaled, or
      subcutaneous) exposure to a hapten in a previously sensitized individual.
      Medicaments are the most common cause of SCD in the adult population, but other
      chemicals like nickel, cobalt, balsam of Peru, and formaldehyde have been
      implicated as well. Few reports in children exist to date. Dietary restriction
      has shown to be of some benefit in managing some adult patients. We present a
      case series of 8 pediatric patients diagnosed with SCD from the contact
      dermatology clinic, who showed marked improvement of their dermatitis after
      adequate dietary avoidance. We review common presentations of chemicals causing
      SCD in children and potential dietary modifications.

PMID- 20807368
TI  - Predictors of direct costs of diabetes care in pediatric patients with type 1
      diabetes.
AB  - OBJECTIVE: This study examines factors that predict elevated direct costs of
      pediatric patients with type 1 diabetes. METHODS: A cohort of 784 children with
      type 1 diabetes at least 6 months postdiagnosis and managed by pediatric
      endocrinologists at Texas Children's Hospital were included in this study. Actual
      reimbursed costs from January 2004 to December 2005 were obtained. Medication and
      supply costs were based on estimates from insulin dosage and type of insulin
      regimen prescribed, respectively. We examined utilization of care, total diabetes
      related direct medical costs, and predictors of direct costs and hospitalization.
      RESULTS: Annually, 7% (58/784) of patients (excluding initial hospitalization at
      diagnosis) had a diabetes-related hospitalization and median length of stay was
      days. Mean total diabetes-related direct cost per person-year was $4730 [95%
      confidence interval (CI), 4516-4944]. Supplies accounted for 38% and medications
      33% of costs, respectively. Older age, hemoglobin A(1C) (HbA(1C) ) > 8.5%, use of
      a multi-injection or pump regimen, living in a non-married household, and female
      gender were associated with higher annual costs. HbA(1C) > 8.5%, living in a non
      married household, and female gender increased the odds of a diabetes-related
      hospitalization. DISCUSSION: Better metabolic control in patients with type 1
      diabetes was associated with lower direct medical costs and lower odds of
      hospitalization. Marital status of the primary caregiver, irrespective of type of
      insurance, impacts the patient's healthcare costs and risk of hospitalization.
      This large single-center US study analyzes cost distribution in children with
      diabetes and is informative for payers and providers focused on effective
      management and improving healthcare costs.

PMID- 20807369
TI  - The discovery of the microphthalmia locus and its gene, Mitf.
AB  - The history of the discovery of the microphthalmia locus and its gene, now called
      Mitf, is a testament to the triumph of serendipity. Although the first
      microphthalmia mutation was discovered among the descendants of a mouse that was
      irradiated for the purpose of mutagenesis, the mutation most likely was not
      radiation induced but occurred spontaneously in one of the parents of a later
      breeding. Although Mitf might eventually have been identified by other molecular
      genetic techniques, it was first cloned from a chance transgene insertion at the
      microphthalmia locus. And although Mitf was found to encode a member of a well
      known transcription factor family, its analysis might still be in its infancy had
      Mitf not turned out to be of crucial importance for the physiology and pathology
      of many distinct organs, including eye, ear, immune system, bone, and skin, and
      in particular for melanoma. In fact, near seven decades of Mitf research have led
      to many insights about development, function, degeneration, and malignancies of a
      number of specific cell types, and it is hoped that these insights will one day
      lead to therapies benefitting those afflicted with diseases originating in these
      cell types.

PMID- 20807370
TI  - Synergistic metabolism in hybrid corn indicates bottlenecks in the carotenoid
      pathway and leads to the accumulation of extraordinary levels of the
      nutritionally important carotenoid zeaxanthin.
AB  - Lutein and zeaxanthin cannot be synthesized de novo in humans, and although
      lutein is abundant in fruit and vegetables, good dietary sources of zeaxanthin
      are scarce. Certain corn varieties provide adequate amounts because the ratio of
      endosperm beta:epsilon lycopene cyclase activity favours the beta
      carotene/zeaxanthin branch of the carotenoid pathway. We previously described a
      transgenic corn line expressing the early enzymes in the pathway (including
      lycopene beta-cyclase) and therefore accumulating extraordinary levels of beta
      carotene. Here, we demonstrate that introgressing the transgenic mini-pathway
      into wild-type yellow endosperm varieties gives rise to hybrids in which the
      beta:epsilon ratio is altered additively. Where the beta:epsilon ratio in the
      genetic background is high, introgression of the mini-pathway allows zeaxanthin
      production at an unprecedented 56 MUg/g dry weight. This result shows that
      metabolic synergy between endogenous and heterologous pathways can be used to
      enhance the levels of nutritionally important metabolites.

PMID- 20807371
TI  - A root is a root is a root? Water uptake rates of Citrus root orders.
AB  - Knowledge about the physiological function of root orders is scant. In this
      study, a system to monitor the water flux among root orders was developed using
      miniaturized chambers. Different root orders of 4-year-old Citrus volkameriana
      trees were analysed with respect to root morphology and water flux. The eight
      root orders showed a broad overlap in diameter, but differences in tissue
      densities and specific root area (SRA) were clearly distinguishable. Thirty per
      cent of the root branch biomass but 50% of the surface area (SA) was possessed by
      the first root order, while the fifth accounted for 5% of the SA (20% biomass).
      The root order was identified as a determinant of water flux. First-order roots
      showed a significantly higher rate of water uptake than the second and third root
      orders, whereas the fourth and fifth root orders showed water excess. The water
      excess suggested the occurrence of hydraulic redistribution (HR) as a result of
      differences in osmotic potentials. We suggest that plants may utilize hydraulic
      redistribution to prevent coarse root desiccation and/or to increase nutrient
      acquisition. Our study showed that the novel 'miniature depletion chamber' method
      enabled direct measurement of water fluxes per root order and can be a major tool
      for future studies on root order traits.

PMID- 20807372
TI  - Increased intracellular H2O2 availability preferentially drives glutathione
      accumulation in vacuoles and chloroplasts.
AB  - One biochemical response to increased H2O2 availability is the accumulation of
      glutathione disulphide (GSSG), the disulphide form of the key redox buffer
      glutathione. It remains unclear how this potentially important oxidative stress
      response impacts on the different sub-cellular glutathione pools. We addressed
      this question by using two independent in situ glutathione labelling techniques
      in Arabidopsis wild type (Col-0) and the GSSG-accumulating cat2 mutant. A
      comparison of in situ labelling with monochlorobimane (MCB) and in vitro
      labelling with monobromobimane (MBB) revealed that, whereas in situ labelling of
      Col-0 leaf glutathione was complete within 2 h incubation, about 50% of leaf
      glutathione remained inaccessible to MCB in cat2. High-performance liquid
      chromatography (HPLC) and enzymatic assays showed that this correlated tightly
      with the glutathione redox state, pointing to significant in vivo pools of GSSG
      in cat2 that were unavailable for MCB labelling. Immunogold labelling of leaf
      sections to estimate sub-cellular glutathione distribution showed that the
      accumulated GSSG in cat2 was associated with only a minor increase in cytosolic
      glutathione but with a 3- and 10-fold increase in plastid and vacuolar pools,
      respectively. The data are used to estimate compartment-specific glutathione
      concentrations under optimal and oxidative stress conditions, and the
      implications for redox homeostasis and signalling are discussed.

PMID- 20807373
TI  - Supra-optimal expression of the cold-regulated OsMyb4 transcription factor in
      transgenic rice changes the complexity of transcriptional network with major
      effects on stress tolerance and panicle development.
AB  - The R2R3-type OsMyb4 transcription factor of rice has been shown to play a role
      in the regulation of osmotic adjustment in heterologous overexpression studies.
      However, the exact composition and organization of its underlying transcriptional
      network has not been established to be a robust tool for stress tolerance
      enhancement by regulon engineering. OsMyb4 network was dissected based on
      commonalities between the global chilling stress transcriptome and the
      transcriptome configured by OsMyb4 overexpression. OsMyb4 controls a hierarchical
      network comprised of several regulatory sub-clusters associated with cellular
      defense and rescue, metabolism and development. It regulates target genes either
      directly or indirectly through intermediary MYB, ERF, bZIP, NAC, ARF and CCAAT
      HAP transcription factors. Regulatory sub-clusters have different combinations of
      MYB-like, GCC-box-like, ERD1-box-like, ABRE-like, G-box-like, as1/ocs/TGA-like,
      AuxRE-like, gibberellic acid response element (GARE)-like and JAre-like cis
      elements. Cold-dependent network activity enhanced cellular antioxidant capacity
      through radical scavenging mechanisms and increased activities of phenylpropanoid
      and isoprenoid metabolic processes involving various abscisic acid (ABA),
      jasmonic acid (JA), salicylic acid (SA), ethylene and reactive oxygen species
      (ROS) responsive genes. OsMyb4 network is independent of drought response element
      binding protein/C-repeat binding factor (DREB/CBF) and its sub-regulons operate
      with possible co-regulators including nuclear factor-Y. Because of its upstream
      position in the network hierarchy, OsMyb4 functions quantitatively and
      pleiotrophically. Supra-optimal expression causes misexpression of alternative
      targets with costly trade-offs to panicle development.

PMID- 20807374
TI  - The transcription factor SlAREB1 confers drought, salt stress tolerance and
      regulates biotic and abiotic stress-related genes in tomato.
AB  - Members of the abscisic acid-responsive element binding protein (AREB)/abscisic
      acid-responsive element binding factor (ABF) subfamily of basic leucine zipper
      (bZIP) transcription factors have been implicated in abscisic acid (ABA) and
      abiotic stress responses in plants. Here we describe two members identified in
      cultivated tomato (Solanum lycopersicum), named SlAREB1 and SlAREB2. Expression
      of SlAREB1 and SlAREB2 is induced by drought and salinity in both leaves and root
      tissues, although that of SlAREB1 was more affected. In stress assays, SlAREB1
      overexpressing transgenic tomato plants showed increased tolerance to salt and
      water stress compared to wild-type and SlAREB1-down-regulating transgenic plants,
      as assessed by physiological parameters such as relative water content (RWC),
      chlorophyll fluorescence and damage by lipoperoxidation. In order to identify
      SlAREB1 target genes responsible for the enhanced tolerance, microarray and cDNA
      amplified fragment length polymorphism (AFLP) analyses were performed. Genes
      encoding oxidative stress-related proteins, lipid transfer proteins (LTPs),
      transcription regulators and late embryogenesis abundant proteins were found
      among the up-regulated genes in SlAREB1-overexpressing lines, especially in
      aerial tissue. Notably, several genes encoding defence proteins associated with
      responses to biotic stress (e.g. pathogenesis-related proteins, protease
      inhibitors, and catabolic enzymes) were also up-regulated by SlAREB1
      overexpression, suggesting that this bZIP transcription factor is involved in ABA
      signals that participate in abiotic stress and possibly in response to pathogens.

PMID- 20807375
TI  - OsEDR1 negatively regulates rice bacterial resistance via activation of ethylene
      biosynthesis.
AB  - Rice OsEDR1 is a sequence ortholog of Arabidopsis EDR1. However, its molecular
      function is unknown. We show here that OsEDR1-suppressing/knockout (KO) plants,
      which developed spontaneous lesions on the leaves, have enhanced resistance to
      Xanthomonas oryzae pv. oryzae (Xoo) causing bacterial blight disease. This
      resistance was associated with increased accumulation of salicylic acid (SA) and
      jasmonic acid (JA), induced expression of SA- and JA-related genes and suppressed
      accumulation of 1-aminocyclopropane-1-carboxylic acid (ACC), the direct precursor
      of ethylene, and expression of ethylene-related genes. OsEDR1-KO plants also
      showed suppressed production of ethylene. Knockout of OsEDR1 suppressed the ACC
      synthase (ACS) gene family, which encodes the rate-limiting enzymes of ethylene
      biosynthesis by catalysing the formation of ACC. The lesion phenotype and
      enhanced bacterial resistance of the OsEDR1-KO plants was partly complemented by
      the treatment with ACC. ACC treatment was associated with decreased SA and JA
      biosynthesis in OsEDR1-KO plants. In contrast, aminoethoxyvinylglycine, the
      inhibitor of ethylene biosynthesis, promoted expression of SA and JA synthesis
      related genes in OsEDR1-KO plants. These results suggest that ethylene is a
      negative signalling molecule in rice bacterial resistance. In the rice-Xoo
      interaction, OsEDR1 transcriptionally promotes the synthesis of ethylene that, in
      turn, suppresses SA- and JA-associated defence signalling.

PMID- 20807377
TI  - The effect and mechanism of action of carbocysteine on airway bacterial load in
      rats chronically exposed to cigarette smoke.
AB  - BACKGROUND AND OBJECTIVE: Carbocysteine (S-carboxymethylcysteine) is a mucoactive
      drug with in vitro free radical scavenging and anti-inflammatory properties.
      Several clinical trials have indicated that carbocysteine reduces exacerbation
      rates in COPD. In the present study, the effect of carbocysteine on the airway
      load of Haemophilus influenzae was assessed in rats chronically exposed to
      cigarette smoke (CS). In addition, the effects of carbocysteine on airway mucus
      hypersecretion and mucociliary clearance (MCC) associated with the adherence and
      clearance of H. influenzae were investigated. METHODS: Wistar rats were randomly
      divided into control, carbocysteine vehicle, CS exposure and carbocysteine
      treatment groups. After 12 weeks, rats were selected for quantitative inoculation
      of H. influenzae. BAL fluid and lungs were collected aseptically after 3 h for
      quantitative culture of H. influenzae. MCC was measured by quantifying the
      clearance of (99m)Tc-Sc. Goblet cell metaplasia and the presence of mucoid matter
      were evaluated by Alcian blue/periodic acid-Schiff staining. Mucin 5AC (Muc5AC)
      expression was detected by western blotting and real-time reverse transcription
      PCR. RESULTS: Exposure to CS increased airway H. influenzae load, aggravated
      mucus hypersecretion and delayed MCC. Treatment with carbocysteine decreased
      airway H. influenzae load, and attenuated airway mucus hypersecretion, with
      improved MCC associated with adherence and clearance of H. influenzae.
      CONCLUSIONS: These results suggest that carbocysteine may be beneficial in
      patients with COPD by increasing the clearance of bacteria and decreasing
      bacterial load.

PMID- 20807376
TI  - The bifunctional abiotic stress signalling regulator and endogenous RNA silencing
      suppressor FIERY1 is required for lateral root formation.
AB  - The Arabidopsis FIERY1 (FRY1) locus was originally identified as a negative
      regulator of stress-responsive gene expression and later shown to be required for
      suppression of RNA silencing. In this study we discovered that the FRY1 locus
      also regulates lateral root formation. Compared with the wild type, fry1 mutant
      seedlings generated significantly fewer lateral roots under normal growth
      conditions and also exhibited a dramatically reduced sensitivity to auxin in
      inducing lateral root initiation. Using transgenic plants that overexpress a
      yeast homolog of FRY1 that possesses only the 3', 5'-bisphosphate nucleotidase
      activity but not the inositol 1-phosphatase activity, we demonstrated that the
      lateral root phenotypes in fry1 result from loss of the nucleotidase activity.
      Furthermore, a T-DNA insertion mutant of another RNA silencing suppressor, XRN4
      (but not XRN2 or XRN3), which is an exoribonuclease that is inhibited by the
      substrate of the FRY1 3', 5'-bisphosphate nucleotidase, exhibits similar lateral
      root defects. Although fry1 and xrn4 exhibited reduced sensitivity to ethylene,
      our experiments demonstrated that restoration of ethylene sensitivity in the fry1
      mutant is not sufficient to rescue the lateral root phenotypes of fry1. Our
      results indicate that RNA silencing modulated by FRY1 and XRN4 plays an important
      role in shaping root architecture.

PMID- 20807378
TI  - Strategic appraisal of environmental risks: a contrast between the United
      Kingdom's Stern Review on the Economics of Climate Change and its Committee on
      Radioactive Waste Management.
AB  - In this article, we compare two high-profile strategic policy reviews undertaken
      for the U.K. government on environmental risks: radioactive waste management and
      climate change. These reviews took very different forms, both in terms of
      analytic approach and deliberation strategy. The Stern Review on the Economics of
      Climate Change was largely an exercise in expert modeling, building, within a
      cost-benefit framework, an argument for immediate reductions in carbon emissions.
      The Committee on Radioactive Waste Management, on the other hand, followed a much
      more explicitly deliberative and participative process, using multicriteria
      decision analysis to bring together scientific evidence and stakeholder and
      public values. In this article, we ask why the two reviews were different, and
      whether the differences are justified. We conclude that the differences were
      mainly due to political context, rather than the underpinning science, and as a
      consequence that, while in our view "fit for purpose," they would both have been
      stronger had they been less different. Stern's grappling with ethical issues
      could have been strengthened by a greater degree of public and stakeholder
      engagement, and the Committee on Radioactive Waste Management's handling of
      issues of uncertainty could have been strengthened by the explicitly
      probabilistic framework of Stern.

PMID- 20807379
TI  - Evaluation of the productivity decrease risk due to a future increase in tropical
      cyclone intensity in Japan.
AB  - A number of scientists have recently conducted research that shows that tropical
      cyclone intensity is likely to increase in the future. This would result in an
      increase in the damage along with a decrease in economic productivity due to
      precautionary cessation of the economic activity of the affected areas during the
      passage of the cyclone. The economic effect of this stop in economic activity is
      a phenomenon that has not received much attention in the past, and the cumulative
      effect that it can have on the Japanese economy over the next 75 years has never
      been evaluated. The starting point for the evaluation of the economic risks is
      the change in the patterns of tropical cyclone intensity suggested by Knutson and
      Tuleya. The results obtained show how a significant decrease in the overall
      productivity of the country could be expected, which could lower GDP by between
      6% and 13% by 2085.

PMID- 20807380
TI  - Can environmental insurance succeed where other strategies fail? The case of
      underground storage tanks.
AB  - Private risk reduction will be socially efficient only when firms are liable for
      all the damage that they cause. We find that environmental insurance can achieve
      social efficiency even when two traditional policy instruments--ex post fines and
      risk management mandates with ex ante fines--do not. Inefficiency occurs with ex
      post fines, when small firms declare bankruptcy and escape their liabilities,
      limiting the incentives from this policy tool. Firms ignore mandates to implement
      efficient risk management because regulatory agencies do not have sufficient
      resources to monitor every firm. The evolution of the U.S. Environmental
      Protection Agency's and states' underground storage tank programs suggests that
      mandating environmental insurance can address inefficiency due to small firms
      declaring bankruptcy. Comparing insurance mandates to risk management mandates,
      the burden on a regulator is lower if all it has to do is to confirm that the
      firm has insurance rather than that the firm has actually, and effectively,
      implemented required management practices. For underground storage tanks, we show
      that insurance lowered toxic releases.

PMID- 20807381
TI  - Cyber security risk management: public policy implications of correlated risk,
      imperfect ability to prove loss, and observability of self-protection.
AB  - The correlated nature of security breach risks, the imperfect ability to prove
      loss from a breach to an insurer, and the inability of insurers and external
      agents to observe firms' self-protection efforts have posed significant
      challenges to cyber security risk management. Our analysis finds that a firm
      invests less than the social optimal levels in self-protection and in insurance
      when risks are correlated and the ability to prove loss is imperfect. We find
      that the appropriate social intervention policy to induce a firm to invest at
      socially optimal levels depends on whether insurers can verify a firm's self
      protection levels. If self-protection of a firm is observable to an insurer so
      that it can design a contract that is contingent on the self-protection level,
      then self-protection and insurance behave as complements. In this case, a social
      planner can induce a firm to choose the socially optimal self-protection and
      insurance levels by offering a subsidy on self-protection. We also find that
      providing a subsidy on insurance does not provide a similar inducement to a firm.
      If self-protection of a firm is not observable to an insurer, then self
      protection and insurance behave as substitutes. In this case, a social planner
      should tax the insurance premium to achieve socially optimal results. The results
      of our analysis hold regardless of whether the insurance market is perfectly
      competitive or not, implying that solely reforming the currently imperfect
      insurance market is insufficient to achieve the efficient outcome in cyber
      security risk management.

PMID- 20807382
TI  - Development of aerobic and anaerobic power in adolescent rowers: a 5-year follow
      up study.
AB  - We aimed to determine whether the physical and physiological superiority of early
      maturing rowing athletes, observed at ages 12-13 years, over that of their late
      maturing counterparts observed at the same ages, still persists at 17-18 years of
      age, when all adolescent athletes are expected to have completed pubertal
      development. We hypothesized that this superiority of early maturers would not be
      observed at reassessment, as late maturers would have likely "caught up" with
      their early-maturing peers. Twenty-one male rowers were assessed at age 12.8 +/-
      0.5 years and again at 17.5 +/- 0.5 years (mean +/- SD). They were divided into
      groups of early-maturing and late-maturing rowing athletes based on Tanner's
      sexual maturity ratings. A two-way repeated-measures MANOVA followed by a series
      of ANOVAs with one within-subject factor (time) and one between-subject factor
      (group) indicated significant (P<=0.003) within-subject and between-subjects main
      effects for lean body mass (LBM), maximal oxygen uptake (VO2max), and mean power
      (MP). The group * time interaction effects were significant for LBM (P=0.003),
      VO2max (P=0.004), but not for MP (P=0.171). Over 5 years, early-maturers'
      advantage dwindled in terms of LBM (+38% to +9%), VO2max (+47% to +9%), and MP
      (+76% to +15%); however, these differences may still be considered practically
      relevant. The proposed hypothesis was not supported.

PMID- 20807383
TI  - Lower extremity joint loading during level walking with Masai barefoot technology
      shoes in overweight males.
AB  - The purpose of this study was to evaluate the effects of Masai barefoot
      technology (MBT) shoes on lower extremity joint loading in overweight males
      during level walking. Therefore, lower extremity kinematics, kinetics, and muscle
      electromyographic signals of the vastus lateralis (VL), biceps femoris (BF), and
      gastrocnemius medialis (GM) were recorded in 10 overweight males at a self-chosen
      walking speed with MBT shoes and conventional shoes. Selected peak joint moments,
      maximal joint force loading rates, mean muscle intensities, and co-activation
      indices of the VL/BF, as well as of the VL/GM were analyzed and compared for the
      two shoe conditions using paired Student's t-tests (alpha=0.05). Results showed
      that walking with MBT shoes reduced first peak knee adduction moments in
      overweight subjects. During midstance and terminal stance, increases in VL/GM co
      activation, accompanied by increases in VL and GM (only terminal stance)
      intensities were found for the MBT situation. Kinetic variables analyzed to
      assess ankle and hip joint loading did not exhibit any statistical differences.
      These results suggest that using MBT shoes diminishes medial compartment loads at
      the knee without overloading hip or ankle joints in overweight males. However,
      the additional muscle loading should not be overlooked, and warrants further
      investigation.

PMID- 20807384
TI  - Asthma is more prevalent in elite swimming adolescents despite better mental and
      physical health.
AB  - An increased risk of developing asthma has been reported among swimmers exposed
      to chloramine in pool arenas. The aim of the present study was to compare the
      prevalence of asthma and respiratory symptoms among elite aspiring swimmers
      compared with age-matched controls with different degrees of physical activity.
      We also aimed to relate these findings to mental and psychosocial factors. One
      hundred and one elite swimmers and 1628 age-matched controls answered a
      questionnaire containing questions about respiratory symptoms, lifestyle factors,
      mental and physical well-being. The controls were divided into three different
      groups according to the degree of physical activity, no physical activity,
      recreational training and elite training. Swimmers reported significantly more
      asthma symptoms, with 36.6% having physician-diagnosed asthma, compared with
      16.2% among the controls. Use of regular medication was more common (14.9% vs
      8.0%) and more swimmers reported an exacerbation of their asthma during the
      previous 12 months (16.8%) vs (5.8%) for the controls. Despite an increased
      prevalence of asthma symptoms, the swimmers reported best physical performance
      and best mental and physical well-being. They also had a healthier lifestyle
      without smoking and low alcohol consumption.

PMID- 20807385
TI  - Effect of exercise training on the density of endothelial cells in the white
      adipose tissue of rats.
AB  - We examined the effects of a 9-week exercise training (TR) in Wistar male rats,
      beginning at 4 weeks of age, on the density of endothelial cells (ECs) in
      epididymal white adipose tissue (WAT) and the mRNA expression of angiogenic
      factors in adipose tissue stromal vascular fraction (SVF) cells. The number of
      ECs and mRNA expressions were assessed by lectin staining and real-time reverse
      transcriptase-polymerase chain reaction, respectively. Compared with control (CR)
      rats, TR rats gained weight more slowly and had significantly lower final weight
      of WAT due to the reduction in the size and the number of adipocytes. TR
      significantly increased the number of ECs per square millimeter and per adipocyte
      (1.37- and 1.23-fold, respectively) in WAT. This is probably because the number
      of adipocytes is fewer while the number of ECs is constant in the WAT of TR rats,
      because the regression line of TR rats for adipocyte number-dependent EC number
      was shifted toward the left without significant differences in the slopes between
      groups. TR also induced the upregulation of mRNA expression of vascular
      endothelial growth factor (Vegf)-A and Vegf-receptor-2 in SVF cells, thereby
      retaining a constant number of ECs in the WAT.

PMID- 20807386
TI  - Injury incidence in hip hop dance.
AB  - Hip hop dance has rapidly become a popular international art form. There is
      limited information on injury patterns in this population. The purpose of this
      study was to determine injury incidence and patterns among three groups of hip
      hop dancers. Three hundred and twelve intermediate, advanced, and expert hip hop
      dancers were recruited at battles, dance conferences, clubs, and on dance related
      web sites within the United States and internationally. A Web-based survey was
      conducted over a 6-month period. Inclusion criteria included intermediate and
      advanced level dancers over the age of 13. Dancers were divided into three main
      categories: Breakers, Popper/Lockers, and New Schoolers. Separate analysis of
      variances were used to compare injury pattern differences between groups. Two
      hundred and thirty-two dancers reported a total of 738 injuries. Five hundred and
      six of these (sustained by 205 dancers) were time-loss (TL) injuries. Annual
      injury incidence was 237% (162% involving TL). Lower extremity injuries were 52%
      and upper extremity injuries 32% of total injuries. Breakers had a higher injury
      incidence compared with Popper/Lockers, and New Schoolers. Hip hop dancers report
      injury rates that are higher than other dance forms but similar to gymnastics.
      These dancers should be educated concerning injury prevention, biomechanics, and
      use of protective equipment.

PMID- 20807387
TI  - Diurnal evolution of cycling biomechanical parameters during a 60-s Wingate test.
AB  - The purpose of this study was to assess the evolution of pedaling kinetics and
      kinematics during a short-term fatigue cycling exercise at two times of day.
      Twenty active male subjects were asked to perform a 60-s Wingate test against a
      constant braking resistance during two experimental sessions at 06:00 and 18:00
      hours, i.e., very close to the hours of core temperature values, which are,
      respectively, the lowest and the highest. The results showed that the fatigue
      index was higher (P<0.05) at 18:00 hours (71.4%) than at 06:00 hours (69.2%) and
      power output was higher (P<0.05) in the evening than in the morning during the
      first 20 s of the test, after which no difference was observed. Taken together,
      these results showed a greater progression of fatigue in the evening than in the
      morning. The diurnal variations in performance and fatigue were associated
      (P<0.001) with diurnal changes in cycling kinematic parameters, characterized by
      a reduction in the range of motion of the ankle angle in the evening. These
      findings show that a time-of-day effect on movement patterns occurs during an
      anaerobic cycling exercise and that this phenomenon has a direct influence on
      performance and fatigue.

PMID- 20807388
TI  - Stress fractures in elite male football players.
AB  - The objective was to investigate the incidence, type and distribution of stress
      fractures in professional male football players. Fifty-four football teams,
      comprising 2379 players, were followed prospectively for 189 team seasons during
      the years 2001-2009. Team medical staff recorded individual player exposure and
      time-loss injuries. The first team squads of 24 clubs selected by UEFA as
      belonging to the 50 best European teams, 15 teams of the Swedish Super League and
      15 teams playing their home matches on artificial turf pitches were included. In
      total, 51 stress fractures occurred during 1,180,000 h of exposure, giving an
      injury incidence of 0.04 injuries/1000 h. A team of 25 players can therefore
      expect one stress fracture every third season. All fractures affected the lower
      extremities and 78% the fifth metatarsal bone. Stress fractures to the fifth
      metatarsal bone, tibia or pelvis caused absences of 3-5 months. Twenty-nine
      percent of the stress fractures were re-injuries. Players that sustained stress
      fractures were significantly younger than those that did not. Stress fractures
      are rare in men's professional football but cause long absences. Younger age and
      intensive pre-season training appear to be risk factors.

PMID- 20807389
TI  - Physiological and anthropometric characteristics of junior cyclists of different
      specialties and performance levels.
AB  - This study analyzes the anthropometric and physiological characteristics of
      junior cyclists within different cycling specialties and different performance
      levels. One hundred and thirty-two junior riders (16.8 +/- 0.6 years, 177 +/- 6
      cm, 66.3 +/- 6.7 kg) were tested for anthropometric, aerobic and anaerobic
      parameters. Cyclists were classified within specialties [uphill (UH) flat terrain
      (FT) all terrain (AT) and sprint (SP)] and performance levels, based on a
      seasonal ranking [low level (LL) medium level (ML) and high level (HL)]. The
      results of the two-way analysis of variance showed that FT and SP have greater
      body dimensions than UH and AT (P<0.001). Concerning the relative aerobic
      parameters, AT and UH have higher values (P<0.001) than FT and SP [maximal oxygen
      uptake (VO(2max) ): 69.4 +/- 3.6, 67.5 +/- 5.0, 62.8 +/- 4.5 and 61.9 +/- 4.1
      mL/kg/min, respectively] while absolute parameters resulted higher for FT and AT
      (P<=0.008). The relative power produced in the 5 s test was higher (P<0.001) for
      AT and SP than FT and UH (16.7 +/- 1.1, 16.6 +/- 0.6, 14.9 +/- 1.7 and 14.4 +/-
      1.7 W/kg, respectively). Concerning the performance level, only the age and the
      aerobic parameters resulted differently within levels (VO(2max) : HL=67.3 +/-
      4.9, ML=65.5 +/- 5.1 and LL=63.3 +/- 5.2 mL/kg/min), with the highest values for
      HL (P<=0.007). In conclusion, juniors are specialized in the same way as
      professional cyclists and the aerobic characteristics are confirmed as
      significant in the performance level assessment.

PMID- 20807390
TI  - Central and peripheral fatigue kinetics during exhaustive constant-load cycling.
AB  - The kinetics of central and peripheral fatigue development during an intensive
      constant-load cycling exercise was evaluated to better understand the mechanisms
      of task failure. Thirteen males cycled to exhaustion at 80% of maximal power
      output in intermittent bouts of 6 min of exercise with 4-min break between bouts
      to assess quadriceps fatigue with maximal voluntary contractions and single (1
      Hz), paired (10 and 100 Hz) potentiated and interpolated magnetic stimulations of
      the femoral nerve (TwQ). Surface electromyographic signals (EMG) of the
      quadriceps muscles were recorded during stimulations and cycling. Total cycling
      duration (TCD) was 27 min 38 s+/-7 min 48 s. The mechanical response evoked by
      magnetic stimulation decreased mostly during the first half of TCD (TwQ1 Hz
      reduction: -34.4+/-12.2% at 40% TCD and -44.8+/-9.2% at exhaustion; P<0.001),
      while a reduction in maximum voluntary activation was present toward the end of
      exercise only (-5.4+/-4.8% and -6.4+/-5.6% at 80% TCD and exhaustion,
      respectively; P<0.01). The increase in quadriceps EMG during cycling was
      significantly correlated to the TwQ reduction for the rectus femoris (r(2) =0.20
      at 1 Hz, r(2) =0.47 at 100 Hz, all P<=0.001). We conclude that peripheral fatigue
      develops early during constant-load intense cycling and is compensated by
      additional motor drive, while central fatigue appears to be associated with task
      failure.

PMID- 20807391
TI  - Epicardial cardiac rhythm devices for dialysis patients: minimizing the risk of
      infection and preserving central veins.
AB  - Transvenous leads of cardiac rhythm devices (CRDs) are known to cause central
      stenosis and are vulnerable to contamination during hemodialysis access-related
      bacteremia. In this retrospective study, nine consecutive chronic hemodialysis
      patients with transvenous CRD infection due to dialysis access-related bacteremia
      and recurrent central stenosis are presented. Four patients with tunneled
      hemodialysis catheters (TDCs) and three with arteriovenous grafts experienced
      access-related bacteremia that spread to the transvenous CRD. Two patients
      required repeated angioplasty procedures (less than 3 months apart) for central
      venous stenosis. Transvenous CRD was removed and replaced with an epicardial
      system in all. One patient with TDC switched to peritoneal dialysis and did not
      experience infection of the epicardial system despite two episodes of
      peritonitis. The remaining TDC (n=3) and graft patients (n=3) received a new TDC
      after the resolution of bacteremia. While all six experienced on average 1.5
      episodes of catheter-related bacteremia (average follow-up = 14.5 months), none
      developed infection of the epicardial system. The patients with central stenosis
      have required only one angioplasty each for the past 8 and 6 months. To the best
      of our knowledge this is the first study to suggest that an epicardial approach
      might be a preferred method over transvenous leads for chronic hemodialysis
      patients.

PMID- 20807392
TI  - Emerging zoonotic diseases in a changed world: strategic vision or fire-fighting?

PMID- 20807393
TI  - Risk factors associated with Salmonella status of broiler flocks delivered to
      grow-out farms.
AB  - In a prospective field observational study in the southeastern USA, we sampled
      gastrointestinal (GI) tracts from chicks of 65 broiler flocks delivered to
      conventional grow-out farms for rearing. The flocks were hatched at seven broiler
      hatcheries. The mean within-flock prevalence of Salmonella-positive samples was
      6.5% and ranged from 0% to 86.7%. Of the 65 flocks studied, 25 (38.5%) had at
      least one Salmonella-positive sample. Accounting for confounding variability
      among the hatcheries and broiler companies, we tested whether the probability of
      detecting Salmonella in GI tracts of the chicks delivered was associated with
      certain characteristics of parent breeder flocks; hatchery production volume;
      hatchery ventilation system; hatchery egg-room conditions; egg incubation,
      candling, hatching, eggshell and bird separation, and bird-processing procedures;
      management of hatchery-to-farm transportation; day of week of hatch; weather
      conditions during transportation; or season of the hatch. Two risk factor models
      were adopted. The first model indicated that a greater number of parent flocks,
      manual separation of eggshell and bird, and a greater amount of fluff and feces
      on tray liners used during hatchery-to-farm transportation at delivery were
      associated with increased probability of detecting Salmonella in chick GI tracts,
      whereas a greater number of birds in the delivery vehicle was associated with
      decreased probability. The second model indicated that broiler flocks hatched on
      Tuesdays versus either Mondays or Thursdays (with no hatches on Wednesdays,
      Fridays or week-ends), increased average hatchability of the eggs from the parent
      flocks, and greater amounts of fluff and feces on the transport tray liners at
      delivery were all associated with increased probability of detecting Salmonella
      in chick GI tracts. The results of this study suggest potential management
      decisions to lessen Salmonella contamination of broilers supplied by commercial
      hatcheries and areas for further research.

PMID- 20807394
TI  - Amino acid composition in endothermic vertebrates is biased in the same direction
      as in thermophilic prokaryotes.
AB  - BACKGROUND: Among bacteria and archaea, amino acid usage is correlated with
      habitat temperatures. In particular, protein surfaces in species thriving at
      higher temperatures appear to be enriched in amino acids that stabilize protein
      structure and depleted in amino acids that decrease thermostability. Does this
      observation reflect a causal relationship, or could the apparent trend be caused
      by phylogenetic relatedness among sampled organisms living at different
      temperatures? And do proteins from endothermic and exothermic vertebrates show
      similar differences? RESULTS: We find that the observed correlations between the
      frequencies of individual amino acids and prokaryotic habitat temperature are
      strongly influenced by evolutionary relatedness between the species analysed;
      however, a proteome-wide bias towards increased thermostability remains after
      controlling for phylogeny. Do eukaryotes show similar effects of thermal
      adaptation? A small shift of amino acid usage in the expected direction is
      observed in endothermic ('warm-blooded') mammals and chicken compared to
      ectothermic ('cold-blooded') vertebrates with lower body temperatures; this shift
      is not simply explained by nucleotide usage biases. CONCLUSION: Protein homologs
      operating at different temperatures have different amino acid composition, both
      in prokaryotes and in vertebrates. Thus, during the transition from ectothermic
      to endothermic life styles, the ancestors of mammals and of birds may have
      experienced weak genome-wide positive selection to increase the thermostability
      of their proteins.

PMID- 20807395
TI  - Cost and disease burden of dengue in Cambodia.
AB  - BACKGROUND: Dengue is endemic in Cambodia (pop. estimates 14.4 million), a
      country with poor health and economic indicators. Disease burden estimates help
      decision makers in setting priorities. Using recent estimates of dengue incidence
      in Cambodia, we estimated the cost of dengue and its burden using disability
      adjusted life years (DALYs). METHODS: Recent population-based cohort data were
      used to calculate direct and productive costs, and DALYs. Health seeking
      behaviors were taken into account in cost estimates. Specific age group incidence
      estimates were used in DALYs calculation. RESULTS: The mean cost per dengue case
      varied from US$36 - $75 over 2006-2008 respectively, resulting in an overall
      annual cost from US$3,327,284 in 2008 to US$14,429,513 during a large epidemic in
      2007. Patients sustain the highest share of costs by paying an average of 78% of
      total costs and 63% of direct medical costs. DALY rates per 100,000 individuals
      ranged from 24.3 to 100.6 in 2007-2008 with 80% on average due to premature
      mortality. CONCLUSION: Our analysis confirmed the high societal and individual
      family burden of dengue. Total costs represented between 0.03 and 0.17% of Gross
      Domestic Product. Health seeking behavior has a major impact on costs. The more
      accurate estimate used in this study will better allow decision makers to account
      for dengue costs particularly among the poor when balancing the benefits of
      introducing a potentially effective dengue vaccine.

PMID- 20807396
TI  - Kaposi's Sarcoma Associated-Herpes Virus (KSHV) Seroprevalence in Pregnant Women
      in South Africa.
AB  - BACKGROUND: Factors previously associated with Kaposi's sarcoma-associated
      herpesvirus (KSHV) transmission in Africa include sexual, familial, and proximity
      to river water. We measured the seroprevalence of KSHV in relation to HIV,
      syphilis, and demographic factors among pregnant women attending public antenatal
      clinics in the Gauteng province of South Africa. METHODS: We tested for
      antibodies to KSHV lytic K8.1 and latent Orf73 antigens in 1740 pregnant women
      attending antenatal clinics who contributed blood to the "National HIV and
      Syphilis Sero-Prevalence Survey - South Africa, 2001". Information on HIV and
      syphilis serology, age, education, residential area, gravidity, and parity was
      anonymously linked to evaluate risk factors for KSHV seropositivity. Clinics were
      grouped by municipality regions and their proximity to the two main river
      catchments defined. RESULTS: KSHV seropositivity (reactive to either lytic K8.1
      and latent Orf73) was nearly twice that of HIV (44.6% vs. 23.1%). HIV and
      syphilis seropositivity was 12.7% and 14.9% in women without KSHV, and 36.1% and
      19.9% respectively in those with KSHV. Women who are KSHV seropositive were 4
      times more likely to be HIV positive than those who were KSHV seronegative (AOR
      4.1 95%CI: 3.4 - 5.7). Although, women with HIV infection were more likely to be
      syphilis seropositive (AOR 1.8 95%CI: 1.3 - 2.4), no association between KSHV and
      syphilis seropositivity was observed. Those with higher levels of education had
      lower levels of KSHV seropositivity compared to those with lower education
      levels. KSHV seropositivity showed a heterogeneous pattern of prevalence in some
      localities. CONCLUSIONS: The association between KSHV and HIV seropositivity and
      a lack of common association with syphilis, suggests that KSHV transmission may
      involve geographical and cultural factors other than sexual transmission.

PMID- 20807397
TI  - The landscape of human genes involved in the immune response to parasitic worms.
AB  - BACKGROUND: More than 2 billion individuals worldwide suffer from helminth
      infections. The highest parasite burdens occur in children and helminth infection
      during pregnancy is a risk factor for preterm delivery and reduced birth weight.
      Therefore, helminth infections can be regarded as a strong selective pressure.
      RESULTS: Here we propose that candidate susceptibility genes for parasitic worm
      infections can be identified by searching for SNPs that display a strong
      correlation with the diversity of helminth species/genera transmitted in
      different geographic areas. By a genome-wide search we identified 3478 variants
      that correlate with helminth diversity. These SNPs map to 810 distinct human
      genes including loci involved in regulatory T cell function and in macrophage
      activation, as well as leukocyte integrins and co-inhibitory molecules. Analysis
      of functional relationships among these genes identified complex interaction
      networks centred around Th2 cytokines. Finally, several genes carrying candidate
      targets for helminth-driven selective pressure also harbour susceptibility
      alleles for asthma/allergy or are involved in airway hyper-responsiveness,
      therefore expanding the known parallelism between these conditions and parasitic
      infections. CONCLUSIONS: Our data provide a landscape of human genes that
      modulate susceptibility to helminths and indicate parasitic worms as one of the
      major selective forces in humans.

PMID- 20807398
TI  - Effect of an armed conflict on relative socioeconomic position of rural
      households: case study from western Cote d'Ivoire.
AB  - BACKGROUND: Current conceptual frameworks on the interrelationship between armed
      conflict and poverty are based primarily on aggregated macro-level data and/or
      qualitative evidence and usually focus on adherents of warring factions. In
      contrast, there is a paucity of quantitative studies about the socioeconomic
      consequences of armed conflict at the micro-level, i.e., noncommitted local
      households and civilians. METHODS: We conducted a secondary analysis of data
      pertaining to risk factors for malaria and neglected tropical diseases.
      Standardized questionnaires were administered to 182 households in a rural part
      of western Cote d'Ivoire in August 2002 and again in early 2004. Between the two
      surveys, the area was subject to intensive fighting in the Ivorian civil war.
      Principal component analysis was applied at the two time points for constructing
      an asset-based wealth-index and categorizing the households in wealth quintiles.
      Based on quintile changes, the households were labeled as 'worse-off', 'even' or
      'better-off'. Statistical analysis tested for significant associations between
      the socioeconomic fates of households and head of household characteristics,
      household composition, village characteristics and self-reported events
      associated with the armed conflict. Most-poor/least-poor ratios and concentration
      indices were calculated to assess equity changes in households' asset possession.
      RESULTS: Of 203 households initially included in the first survey, 21 were lost
      to follow-up. The population in the remaining 182 households shrunk from 1,749 to
      1,625 persons due to migration and natural population changes. However, only weak
      socioeconomic dynamics were observed; every seventh household was defined as
      'worse-off' or 'better-off' despite the war-time circumstances. Analysis of other
      reported demographic and economic characteristics did not clearly identify more
      or less resilient households, and only subtle equity shifts were noted.However,
      the results indicate significant changes in livelihood strategies with a
      significant return to agricultural production and a decrease in the diversity of
      socioeconomic activities. CONCLUSION: Situational constraints and methodological
      obstacles are inherent in conflict settings and hamper conflict-related
      socioeconomic research. Furthermore, sensitive methods to assess and meaningfully
      interpret longitudinal micro-level wealth data from low-income countries are
      lacking. Despite compelling evidence of socioeconomic dynamics triggered by armed
      conflicts at the macro-level, we could not identify similar effects at the micro
      level. A deeper understanding of household profiles that are more resilient to
      armed conflict could help to better prevent and/or alleviate adverse conflict
      related and increasingly civilian-borne socioeconomic effects.

PMID- 20807399
TI  - Meconium pseudocyst secondary to ileum volvulus perforation without peritoneal
      calcification: a case report.
AB  - INTRODUCTION: A case of giant meconium pseudocyst secondary to ileum volvulus
      perforation is presented. Conventional radiographic features of meconium
      peritonitis with secondary meconium pseudocyst formation are well described. Our
      case is unusual in comparison to other cases reported in the literature and needs
      to be reported because the meconium pseudocyst presented without the typical
      ultrasound features (calcifications, polyhydramnios and ascites) and was
      initially identified as an abdominal mass. CASE PRESENTATION: We describe the
      case of a 29-year-old Caucasian woman in her third trimester of pregnancy, in
      which an abdominal mass was detected in the fetus. The newborn was diagnosed in
      the early neonatal period with meconium pseudocyst secondary to ileum volvulus
      perforation. CONCLUSIONS: The prenatal appearance of a meconium pseudocyst can be
      complemented by other signs of bowel obstruction (if present) such as
      polyhydramnios and fetal bowel dilatation. This is an original case report of
      interest to all clinicians in the perinatology and fetal ultrasound field. We
      consider that the utility of this case is the recognition that a meconium
      pseudocyst might appear without the typical ultrasound features and should be
      considered as a differential diagnosis when an echogenic intra-abdominal cyst is
      seen.

PMID- 20807401
TI  - Lung contusion and cavitation with exudative plural effusion following
      extracorporeal shock wave lithotripsy in an adult: a case report.
AB  - INTRODUCTION: Among the complications of extracorporeal shock wave lithotripsy
      are perinephric bleeding and hypertension. CASE PRESENTATION: We describe the
      case of a 31-year-old Asian man with an unusual case of hemoptysis and lung
      contusion and cavitation with exudative plural effusion due to pulmonary trauma
      following false positioning of extracorporeal shock wave lithotripsy.
      Differential diagnoses included pneumonia and pulmonary emboli, but these
      diagnoses were ruled out by the uniformly negative results of a lung perfusion
      scan, Doppler ultrasound, and culture of bronchoalveolar lavage and plural
      effusion, and because our patient showed spontaneous improvement. CONCLUSIONS:
      False positioning of extracorporeal shock wave lithotripsy can cause lung trauma
      presenting as pulmonary contusion and cavitation with plural effusion.

PMID- 20807402
TI  - Status dystonicus resembling the intrathecal baclofen withdrawal syndrome: a case
      report and review of the literature.
AB  - INTRODUCTION: Status dystonicus is a rare but life-threatening disorder
      characterized by increasingly frequent and severe episodes of generalized
      dystonia that may occur in patients with primary or secondary dystonia. Painful
      and repetitive spasms interfere with respiration and may cause metabolic
      disturbances such as hyperpyrexia, dehydration, respiratory insufficiency, and
      acute renal failure secondary to rhabdomyolysis. Intrathecally administered
      baclofen, delivered by an implantable pump system, is widely used for the
      treatment of refractory spasticity. Abrupt cessation of intrathecal baclofen
      infusion has been associated with a severe withdrawal syndrome comprised of
      dystonia, autonomic dysfunction, hyperthermia, end-organ failure and sometimes
      death. The aetiology of this syndrome is not well understood. Status dystonicus
      describes the episodes of acute and life-threatening generalized dystonia, which
      occasionally manifest themselves in patients with dystonic syndromes. CASE
      PRESENTATION: We present the case of a nine-year-old Caucasian boy who
      experienced a severe episode of status dystonicus with no known cause and
      clinical features resembling those described in intrathecal baclofen withdrawal.
      Our patient subsequently underwent the placement of an intrathecal baclofen pump
      without incident. CONCLUSION: The similarity between the clinical features of the
      case we present and those reported in connection to abrupt withdrawal of
      intrathecal baclofen is emphasized. Several drugs, although not intrathecal
      baclofen withdrawal, have previously been associated with status dystonicus. The
      similarity between the life-threatening dystonic episode experienced by our
      patient, and those reported in intrathecal baclofen withdrawal, highlights the
      possibility that, rather than representing a true physiological withdrawal
      syndrome, abrupt withdrawal of intrathecal baclofen may simply precipitate an
      episode of status dystonicus in susceptible individuals. The clinical
      similarities between the intrathecal baclofen withdrawal syndrome and status
      dystonicus have not previously been highlighted.

PMID- 20807403
TI  - Treatment of stasis dermatitis using aminaphtone: a case series.
AB  - INTRODUCTION: Stasis purpura is a common finding in clinical practice and is
      related to vascular alterations. CASE PRESENTATION: Four randomly-selected,
      Caucasian patients (a 45-year-old woman, a 26-year-old man, a 51-year-old man and
      a 56-year-old woman) were treated with aminaphtone for approximately one year.
      For all patients, the brown patches - a sign of stasis purpura - disappeared
      without the appearance of new lesions within this period. CONCLUSION: Aminaphtone
      is a novel proposal in the treatment of stasis purpura when capillary fragility
      is identified.

PMID- 20807400
TI  - Antimalarial drug targets in Plasmodium falciparum predicted by stage-specific
      metabolic network analysis.
AB  - BACKGROUND: Despite enormous efforts to combat malaria the disease still afflicts
      up to half a billion people each year of which more than one million die.
      Currently no approved vaccine is available and resistances to antimalarials are
      widely spread. Hence, new antimalarial drugs are urgently needed. RESULTS: Here,
      we present a computational analysis of the metabolism of Plasmodium falciparum,
      the deadliest malaria pathogen. We assembled a compartmentalized metabolic model
      and predicted life cycle stage specific metabolism with the help of a flux
      balance approach that integrates gene expression data. Predicted metabolite
      exchanges between parasite and host were found to be in good accordance with
      experimental findings when the parasite's metabolic network was embedded into
      that of its host (erythrocyte). Knock-out simulations identified 307
      indispensable metabolic reactions within the parasite. 35 out of 57
      experimentally demonstrated essential enzymes were recovered and another 16
      enzymes, if additionally the assumption was made that nutrient uptake from the
      host cell is limited and all reactions catalyzed by the inhibited enzyme are
      blocked. This predicted set of putative drug targets, shown to be enriched with
      true targets by a factor of at least 2.75, was further analyzed with respect to
      homology to human enzymes, functional similarity to therapeutic targets in other
      organisms and their predicted potency for prophylaxis and disease treatment.
      CONCLUSIONS: The results suggest that the set of essential enzymes predicted by
      our flux balance approach represents a promising starting point for further drug
      development.

PMID- 20807404
TI  - High anorectal malformation in a five-month-old boy: a case report.
AB  - INTRODUCTION: Anorectal malformation, one of the most common congenital defects,
      may present with a wide spectrum of defects. Almost all male patients present
      within first few days of life. CASE PRESENTATION: A five-month-old baby boy of
      Indian origin and nationality presented with anal atresia and associated
      rectourethral prostatic fistula. The anatomy of the malformation and our
      patient's good condition permitted a primary definitive repair of the anomaly. A
      brief review of the relevant literature is included. CONCLUSION: Delayed
      presentation of a patient with high anorectal malformation is rare. The
      appropriate treatment can be rewarding.

PMID- 20807405
TI  - Validity and test-retest reliability of manual goniometers for measuring passive
      hip range of motion in femoroacetabular impingement patients.
AB  - BACKGROUND: The aims of this study were to evaluate the construct validity (known
      group), concurrent validity (criterion based) and test-retest (intra-rater)
      reliability of manual goniometers to measure passive hip range of motion (ROM) in
      femoroacetabular impingement patients and healthy controls. METHODS: Passive hip
      flexion, abduction, adduction, internal and external rotation ROMs were
      simultaneously measured with a conventional goniometer and an electromagnetic
      tracking system (ETS) on two different testing sessions. A total of 15 patients
      and 15 sex- and age-matched healthy controls participated in the study. RESULTS:
      The goniometer provided greater hip ROM values compared to the ETS (range 2.0
      18.9 degrees; P < 0.001); good concurrent validity was only achieved for hip
      abduction and internal rotation, with intraclass correlation coefficients (ICC)
      of 0.94 and 0.88, respectively. Both devices detected lower hip abduction ROM in
      patients compared to controls (P < 0.01). Test-retest reliability was good with
      ICCs higher 0.90, except for hip adduction (0.82-0.84). Reliability estimates did
      not differ between the goniometer and the ETS. CONCLUSIONS: The present study
      suggests that goniometer-based assessments considerably overestimate hip joint
      ROM by measuring intersegmental angles (e.g., thigh flexion on trunk for hip
      flexion) rather than true hip ROM. It is likely that uncontrolled pelvic rotation
      and tilt due to difficulties in placing the goniometer properly and in performing
      the anatomically correct ROM contribute to the overrating of the arc of these
      motions. Nevertheless, conventional manual goniometers can be used with
      confidence for longitudinal assessments in the clinic.

PMID- 20807406
TI  - Oestrogen blocks the nuclear entry of SOX9 in the developing gonad of a marsupial
      mammal.
AB  - BACKGROUND: Hormones are critical for early gonadal development in nonmammalian
      vertebrates, and oestrogen is required for normal ovarian development. In
      contrast, mammals determine sex by the presence or absence of the SRY gene, and
      hormones are not thought to play a role in early gonadal development. Despite an
      XY sex-determining system in marsupial mammals, exposure to oestrogen can
      override SRY and induce ovarian development of XY gonads if administered early
      enough. Here we assess the effect of exogenous oestrogen on the molecular
      pathways of mammalian gonadal development. RESULTS: We examined the expression of
      key testicular (SRY, SOX9, AMH and FGF9) and ovarian (WNT4, RSPO1, FOXL2 and FST)
      markers during gonadal development in the marsupial tammar wallaby (Macropus
      eugenii) and used these data to determine the effect of oestrogen exposure on
      gonadal fate. During normal development, we observed male specific upregulation
      of AMH and SOX9 as in the mouse and human testis, but this upregulation was
      initiated before the peak in SRY expression and 4 days before testicular cord
      formation. Similarly, key genes for ovarian development in mouse and human were
      also upregulated during ovarian differentiation in the tammar. In particular,
      there was early sexually dimorphic expression of FOXL2 and WNT4, suggesting that
      these genes are key regulators of ovarian development in all therian mammals. We
      next examined the effect of exogenous oestrogen on the development of the
      mammalian XY gonad. Despite the presence of SRY, exogenous oestrogen blocked the
      key male transcription factor SOX9 from entering the nuclei of male somatic
      cells, preventing activation of the testicular pathway and permitting
      upregulation of key female genes, resulting in ovarian development of the XY
      gonad. CONCLUSIONS: We have uncovered a mechanism by which oestrogen can regulate
      gonadal development through the nucleocytoplasmic shuttling of SOX9. This may
      represent an underlying ancestral mechanism by which oestrogen promotes ovarian
      development in the gonads of nonmammalian vertebrates. Furthermore, oestrogen may
      retain this function in adult female mammals to maintain granulosa cell fate in
      the differentiated ovary by suppressing nuclear translocation of the SOX9
      protein. See commentary: http://www.biomedcentral.com/1741-7007/8/110.

PMID- 20807407
TI  - The Hand Eczema Trial (HET): Design of a randomised clinical trial of the effect
      of classification and individual counselling versus no intervention among health
      care workers with hand eczema.
AB  - BACKGROUND: Hand eczema is the most frequently recognized occupational disease in
      Denmark with an incidence of approximately 0.32 per 1000 person-years.
      Consequences of hand eczema include chronic severe eczema, prolonged sick leave,
      unemployment, and impaired quality of life. New preventive strategies are needed
      to reduce occupational hand eczema. METHODS/DESIGN: We describe the design of a
      randomised clinical trial to investigate the effects of classification of hand
      eczema plus individual counselling versus no intervention. The trial includes
      health-care workers with hand eczema identified from a self-administered
      questionnaire delivered to 3181 health-care workers in three Danish hospitals.
      The questionnaire identifies the prevalence of hand eczema, knowledge of skin
      protection, and exposures that can lead to hand eczema. At entry, all
      participants are assessed regarding: disease severity (Hand Eczema Severity
      Index); self-evaluated disease severity; number of eruptions; quality of life;
      skin protective behaviour, and knowledge of skin protection. The patients are
      centrally randomised to intervention versus no intervention 1:1 stratified for
      hospital, profession, and severity score. The experimental group undergoes patch
      and prick testing; classification of the hand eczema; demonstration of hand
      washing and appliance of emollients; individual counselling, and a skin-care
      programme. The control group receives no intervention. All participants are
      reassessed after six months. The primary outcome is observer-blinded assessment
      of disease severity and the secondary outcomes are unblinded assessments of
      disease severity; number of eruptions; knowledge of skin protection; skin
      protective behaviour, and quality of life. TRIAL REGISTRATION: The trial is
      registered in ClinicalTrials.Gov, NCT01012453.

PMID- 20807408
TI  - International benchmarking of specialty hospitals. A series of case studies on
      comprehensive cancer centres.
AB  - BACKGROUND: Benchmarking is one of the methods used in business that is applied
      to hospitals to improve the management of their operations. International
      comparison between hospitals can explain performance differences. As there is a
      trend towards specialization of hospitals, this study examines the benchmarking
      process and the success factors of benchmarking in international specialized
      cancer centres. METHODS: Three independent international benchmarking studies on
      operations management in cancer centres were conducted. The first study included
      three comprehensive cancer centres (CCC), three chemotherapy day units (CDU) were
      involved in the second study and four radiotherapy departments were included in
      the final study. Per multiple case study a research protocol was used to
      structure the benchmarking process. After reviewing the multiple case studies,
      the resulting description was used to study the research objectives. RESULTS: We
      adapted and evaluated existing benchmarking processes through formalizing
      stakeholder involvement and verifying the comparability of the partners. We also
      devised a framework to structure the indicators to produce a coherent indicator
      set and better improvement suggestions. Evaluating the feasibility of
      benchmarking as a tool to improve hospital processes led to mixed results. Case
      study 1 resulted in general recommendations for the organizations involved. In
      case study 2, the combination of benchmarking and lean management led in one CDU
      to a 24% increase in bed utilization and a 12% increase in productivity. Three
      radiotherapy departments of case study 3, were considering implementing the
      recommendations.Additionally, success factors, such as a well-defined and small
      project scope, partner selection based on clear criteria, stakeholder
      involvement, simple and well-structured indicators, analysis of both the process
      and its results and, adapt the identified better working methods to the own
      setting, were found. CONCLUSIONS: The improved benchmarking process and the
      success factors can produce relevant input to improve the operations management
      of specialty hospitals.

PMID- 20807410
TI  - Increasing community capacity to prevent childhood obesity: challenges, lessons
      learned and results from the Romp & Chomp intervention.
AB  - BACKGROUND: Obesity is a major public health issue; however, only limited
      evidence is available about effective ways to prevent obesity, particularly in
      early childhood. Romp & Chomp was a community-wide obesity prevention
      intervention conducted in Geelong Australia with a target group of 12,000
      children aged 0-5 years. The intervention had an environmental and capacity
      building focus and we have recently demonstrated that the prevalence of
      overweight/obesity was lower in intervention children, post-intervention.
      Capacity building is defined as the development of knowledge, skills, commitment,
      structures, systems and leadership to enable effective health promotion and the
      aim of this study was to determine if the capacity of the Geelong community,
      represented by key stakeholder organisations, to support healthy eating and
      physical activity for young children was increased after Romp & Chomp. METHODS: A
      mixed methods evaluation with three data sources was utilised. 1) Document
      analysis comprised assessment of the documented formative and intervention
      activities against a capacity building framework (five domains: Partnerships,
      Leadership, Resource Allocation, Workforce Development, and Organisational
      Development); 2) Thematic analysis of key informant interviews (n = 16); and 3)
      the quantitative Community Capacity Index Survey. RESULTS: Document analysis
      showed that the majority of the capacity building activities addressed the
      Partnerships, Resource Allocation and Organisational Development domains of
      capacity building, with a lack of activity in the Leadership and Workforce
      Development domains. The thematic analysis revealed the establishment of
      sustainable partnerships, use of specialist advice, and integration of activities
      into ongoing formal training for early childhood workers. Complex issues also
      emerged from the key informant interviews regarding the challenges of limited
      funding, high staff turnover, changing governance structures, lack of high level
      leadership and unclear communication strategies. The Community Capacity Index
      provided further evidence that the project implementation network achieved a
      moderate level of capacity. CONCLUSIONS: Romp & Chomp increased the capacity of
      organisations, settings and services in the Geelong community to support healthy
      eating and physical activity for young children. Despite this success there are
      important learnings from this mixed methods evaluation that should inform current
      and future community-based public health and health promotion initiatives. TRIAL
      REGISTRATION NUMBER: ANZCTRN12607000374460.

PMID- 20807409
TI  - The impact of maternal protein restriction during rat pregnancy upon renal
      expression of angiotensin receptors and vasopressin-related aquaporins.
AB  - BACKGROUND: Maternal protein restriction during rat pregnancy is known to impact
      upon fetal development, growth and risk of disease in later life. It is of
      interest to understand how protein undernutrition influences the normal maternal
      adaptation to pregnancy. Here we investigated the mechanisms regulating renal
      haemodynamics and plasma volume during pregnancy, in the context of both normal
      and reduced plasma volume expansion. The study focused on expression of renal
      angiotensin receptors (ATR) and vasopressin-related aquaporins (AQP),
      hypothesising that an alteration in the balance of these proteins would be
      associated with pregnancy per se and with compromised plasma volume expansion in
      rats fed a low-protein diet. METHODS: Female Wistar rats were mated and fed a
      control (18% casein) or low-protein (9% casein) diet during pregnancy. Animals
      were anaesthetised on days 5, 10, 15 and 20 of gestation (n = 8/group/time-point)
      for determination of plasma volume using Evans Blue dye, prior to euthanasia and
      collection of tissues. Expression of the ATR subtypes and AQP2, 3 and 4 were
      assessed in maternal kidneys by PCR and western blotting. 24 non-pregnant Wistar
      rats underwent the same procedure at defined points of the oestrous cycle.
      RESULTS: As expected, pregnancy was associated with an increase in blood volume
      and haemodilution impacted upon red blood cell counts and haemoglobin
      concentrations. Expression of angiotensin II receptors and aquaporins 2, 3 and 4
      was stable across all stages of the oestrus cycle. Interesting patterns of intra
      renal protein expression were observed in response to pregnancy, including a
      significant down-regulation of AQP2. In contrast to previous literature and
      despite an apparent delay in blood volume expansion in low-protein fed rats,
      blood volume did not differ significantly between groups of pregnant animals.
      However, a significant down-regulation of AT2R protein expression was observed in
      low-protein fed animals alongside a decrease in creatinine clearance. CONCLUSION:
      Regulatory systems involved in the pregnancy-induced plasma volume expansion are
      susceptible to the effects of maternal protein restriction.

PMID- 20807411
TI  - A transcriptomic approach highlights induction of secondary metabolism in citrus
      fruit in response to Penicillium digitatum infection.
AB  - BACKGROUND: Postharvest losses of citrus fruit due to green mold decay, caused by
      the fungus Penicillium digitaum, have a considerable economic impact. However,
      little is known about the molecular processes underlying the response of citrus
      fruit to P. digitatum. RESULTS: Here we describe the construction of a subtracted
      cDNA library enriched in citrus genes preferentially expressed in response to
      pathogen infection followed by cDNA macroarray hybridization to investigate gene
      expression during the early stages of colonization of the fruit's peel by P.
      digitatum. Sequence annotation of clones from the subtracted cDNA library
      revealed that induction of secondary and amino acid metabolisms constitutes the
      major response of citrus fruits to P. digitatum infection. Macroarray
      hybridization analysis was conducted with RNA from either control, wounded,
      ethylene treated or P. digitatum infected fruit. Results indicate an extensive
      overlap in the response triggered by the three treatments, but also demonstrated
      specific patterns of gene expression in response to each stimulus. Collectively
      our data indicate a significant presence of isoprenoid, alkaloid and
      phenylpropanoid biosynthetic genes in the transcriptomic response of citrus
      fruits to P. digitatum infection. About half of the genes that are up-regulated
      in response to pathogen infection are also induced by ethylene, but many examples
      of ethylene-independent gene regulation were also found. Two notable examples of
      this regulation pattern are the genes showing homology to a caffeine synthase and
      a berberine bridge enzyme, two proteins involved in alkaloid biosynthesis, which
      are among the most induced genes upon P. digitatum infection but are not
      responsive to ethylene. CONCLUSIONS: This study provided the first global picture
      of the gene expression changes in citrus fruit in response to P. digitatum
      infection, emphasizing differences and commonalities with those triggered by
      wounding or exogenous ethylene treatment. Interpretation of the differentially
      expressed genes revealed that metabolism is redirected to the synthesis of
      isoprenes, alkaloids and phenylpropanoids.

PMID- 20807412
TI  - Dynamic analysis of CD127 expression on memory CD8 T cells from patients with
      chronic hepatitis B during telbivudine treatment.
AB  - BACKGROUND: Accumulating evidence supports the theory that expression of CD127 on
      CD8 T cells during the process of antiviral immune response indicates a subset of
      effect CD8 T cells that successfully develop into fully protective memory. CD8 T
      cells expression of CD127 may be used as a predictor to evaluate disease status
      in chronic viral infection. The aim of this study was to investigate the CD127
      expression level on different subsets of CD8 T cell and explore the relationship
      between CD127 expression on CD8 memory T cells and serum hepatitis B virus (HBV)
      DNA and hepatitis B e antigen (HBeAg) levels in patients with chronic hepatitis B
      (CHB). We also aimed to investigate the CD127 expression pattern on CD8 memory T
      cells of CHB patients who were treated with Telbivudine. METHODS/RESULTS: Twenty
      HBeAg-positive CHB patients were selected and treated with telbivudine 600 mg/day
      for 48 weeks. The memory CD8 T cells were characterized by expression of CD45RA
      and CD27 markers. CD127 expression on the CD8 T-cell surface was measured by four
      colour flow cytometry. Our results showed that CD127 expression on memory CD8 T
      cells was reduced in CHB patients. There was a strong negative correlation
      between CD127 expression on memory CD8 T cells and serum HBV DNA and HBeAg levels
      in CHB patients. Moreover, successful antiviral therapy increased CD127
      expression on CD8 memory T cells as well as on HBV-specific CD8 T cells in CHB
      patients. CONCLUSION: These results suggest that diminished CD127 expression on
      CD8 memory T cells of CHB patients is a potential mechanism explaining cellular
      immune function impairment in CHB infection, and that CD127 expression on CD8
      memory T cells is a useful indicator for evaluating the effects of anti-HBV
      therapy.

PMID- 20807413
TI  - Cardiovascular, endocrine and behavioural responses to suckling and permanent
      separation in goats.
AB  - BACKGROUND: Suckling can be a peaceful or vulnerable event for goats and kids,
      whereas, separation is suggested as stressful. The aim of this study was to
      investigate physiology and behaviour in these two different situations in dairy
      goats. METHODS: Four studies were performed with seven goats kept with their
      first-born kid in individual boxes. The goats were videotaped and heart rate and
      arterial blood pressure were recorded every minute by telemetry from parturition
      until 24 hours after separation. One to two days after parturition, Study 1 was
      performed with analyses of heart rate and blood pressure around a suckling. In
      Study 2, performed 3-5 days after parturition, blood sampling was done before,
      during and after suckling. Study 3 was performed 4-6 days post partum, with blood
      sampling before and after a permanent goat and kid separation. In addition,
      vocalisations were recorded after separation. Blood samples were obtained from a
      jugular vein catheter and analysed for plasma cortisol, beta-endorphin, oxytocin,
      and vasopressin concentrations. Study 4 was performed during the first (N1) and
      second nights (N2) after parturition and the nights after Study 2 (N3) and 3
      (N4). Heart rate, blood pressure and time spent lying down were recorded.
      RESULTS: The kids suckled 2 +/- 0.2 times per hour and each suckling bout lasted
      43 +/- 15 s. In Study 1, heart rate and blood pressure did not change
      significantly during undisturbed suckling. In Study 2, plasma cortisol (P <= 0.05
      during suckling and P <= 0.01 five minutes after suckling) and beta-endorphin (P
      <= 0.05) concentrations increased during suckling, but oxytocin and vasopressin
      concentrations did not change. In Study 3, the goats and kids vocalised
      intensively during the first 20 minutes after separation, but the physiological
      variables were not affected. In Study 4, heart rate and arterial blood pressure
      declined gradually after parturition and were lowest during N4 (P <= 0.05) when
      the goats spent longer time lying down than during earlier nights (P <= 0.01
      during N1 and N3 and P <= 0.05 during N2). CONCLUSIONS: Suckling elevated plasma
      cortisol and beta-endorphin concentrations in the goats. The intensive
      vocalisation in the goats after separation, earlier suggested to indicate stress,
      was not accompanied by cardiovascular or endocrine responses.

PMID- 20807414
TI  - Bayesian random local clocks, or one rate to rule them all.
AB  - BACKGROUND: Relaxed molecular clock models allow divergence time dating and
      "relaxed phylogenetic" inference, in which a time tree is estimated in the face
      of unequal rates across lineages. We present a new method for relaxing the
      assumption of a strict molecular clock using Markov chain Monte Carlo to
      implement Bayesian modeling averaging over random local molecular clocks. The new
      method approaches the problem of rate variation among lineages by proposing a
      series of local molecular clocks, each extending over a subregion of the full
      phylogeny. Each branch in a phylogeny (subtending a clade) is a possible location
      for a change of rate from one local clock to a new one. Thus, including both the
      global molecular clock and the unconstrained model results, there are a total of
      2(2n-2) possible rate models available for averaging with 1, 2, ..., 2n - 2
      different rate categories. RESULTS: We propose an efficient method to sample this
      model space while simultaneously estimating the phylogeny. The new method
      conveniently allows a direct test of the strict molecular clock, in which one
      rate rules them all, against a large array of alternative local molecular clock
      models. We illustrate the method's utility on three example data sets involving
      mammal, primate and influenza evolution. Finally, we explore methods to visualize
      the complex posterior distribution that results from inference under such models.
      CONCLUSIONS: The examples suggest that large sequence datasets may only require a
      small number of local molecular clocks to reconcile their branch lengths with a
      time scale. All of the analyses described here are implemented in the open access
      software package BEAST 1.5.4 (http://beast-mcmc.googlecode.com/).

PMID- 20807415
TI  - The participation of NMDA receptors, PKC, and MAPK in the formation of memory
      following operant conditioning in Lymnaea.
AB  - BACKGROUND: Memory is the ability to store, retain, and later retrieve
      information that has been learned. Intermediate term memory (ITM) that persists
      for up to 3 h requires new protein synthesis. Long term memory (LTM) that
      persists for at least 24 h requires: DNA transcription, RNA translation, and the
      trafficking of newly synthesized proteins. It has been shown in a number of
      different model systems that NMDA receptors, protein kinase C (PKC) and mitogen
      activated protein kinase (MAPK) are all involved in the memory formation process.
      RESULTS: Here we show that snails trained in control conditions are capable of
      forming, depending on the training procedure used, either ITM or LTM. However,
      blockage of NMDA receptors (MK 801), inhibition of PKC (GF109203X hydrochloride)
      and MAPK activity (UO126) prevent the formation of both ITM and LTM. CONCLUSIONS:
      The injection of either U0126 or GF109203X, which inhibit MAPK and PKC activity
      respectively, 1 hour prior to training results in the inhibition of both ITM and
      LTM formation. We further found that NMDA receptor activity was necessary in
      order for both ITM and LTM formation.

PMID- 20807417
TI  - Fetal cardiotocography before and after water aerobics during pregnancy.
AB  - OBJECTIVE: To evaluate the effect of moderate aerobic physical activity in water
      on fetal cardiotocography patterns in sedentary pregnant women. METHOD: In a non
      randomized controlled trial, 133 previously sedentary pregnant women participated
      in multiple regular sessions of water aerobics in a heated swimming pool.
      Cardiotocography was performed for 20 minutes before and just after the oriented
      exercise. Cardiotocography patterns were analyzed pre- and post-exercise
      according to gestational age groups (24-27, 28-31, 32-35 and 36-40 weeks).
      Student's t and Wilcoxon, and McNemar tests were used, respectively, to analyze
      numerical and categorical variables. RESULTS: No significant variations were
      found between pre- and post-exercise values of fetal heart rate (FHR), number of
      fetal body movements (FM) or accelerations (A), FM/A ratio or the presence of
      decelerations. Variability in FHR was significantly higher following exercise
      only in pregnancies of 24-27 weeks. CONCLUSIONS: Moderate physical activity in
      water was not associated with any significant alterations in fetal
      cardiotocography patterns, which suggests no adverse effect on the fetus.

PMID- 20807416
TI  - Genetic characterization of the cell-adapted PanAsia strain of foot-and-mouth
      disease virus O/Fujian/CHA/5/99 isolated from swine.
AB  - BACKGROUND: According to Office International Des Epizooties (OIE) Bulletin, the
      PanAsia strain of Foot-and-Mouth Disease Virus (FMDV) was invaded into the
      People's Republic of China in May 1999. It was confirmed that the outbreaks
      occurred in Tibet, Hainan and Fujian provinces. In total, 1280 susceptible
      animals (68 cattle, 1212 swine) were destroyed for the epidemic control.To
      investigate the distinct biological properties, we performed plaque assay,
      estimated the pathogenicity in suckling mice and determined the complete genomic
      sequence of FMDV swine-isolated O/Fujian/CHA/5/99 strain. In addition, a
      molecular modeling was carried out with the external capsid proteins. RESULTS:
      The pathogenicity study showed that O/Fujian/CHA/5/99 had high virulence with
      respect to infection in 3-day-old suckling-mice (LD50 = 10-8.3), compared to
      O/Tibet/CHA/1/99 (LD50 = 10-7.0) which isolated from bovine. The plaque assay was
      distinguishable between O/Fujian/CHA/5/99 and O/Tibet/CHA/1/99 by their plaque
      phenotypes. O/Fujian/CHA/5/99 formed large plaque while O/Tibet/CHA/1/99 formed
      small plaque.The 8,172 nucleotides (nt) of O/Fujian/CHA/5/99 was sequenced, and a
      phylogenetic tree was generated from the complete nucleotide sequences of VP1
      compared with other FMDV reference strains. The identity data showed that
      O/Fujian/CHA/5/99 is closely related to O/AS/SKR/2002 (94.1% similarity). Based
      on multiple sequence alignments, comparison of sequences showed that the
      characteristic nucleotide/amino acid mutations were found in the whole genome of
      O/Fujian/CHA/5/99. CONCLUSION: Our finding suggested that C275T substitution in
      IRES of O/Fujian/CHA/5/99 may induce the stability of domain 3 for the whole
      element function. The structure prediction indicated that most of 14 amino acid
      substitutions are fixed in the capsid of O/Fujian/CHA/5/99 around B-C loop and E
      F loop of VP2 (antigenic site 2), and G-H loop of VP1 (antigenic site 1),
      respectively. These results implicated that these substitutions close to heparin
      binding sites (E136G in VP2, A174 S in VP3) and at antigenic site 1 (T142A, A152T
      and Q153P in VP1) may influence plaque size and the pathogenicity to suckling
      mice.The potential of genetic characterization would be useful for microevolution
      and viral pathogenesis of FMDV in the further study.

PMID- 20807418
TI  - Ectopic corticotropin-releasing hormone (CRH) syndrome from metastatic small cell
      carcinoma: a case report and review of the literature.
AB  - BACKGROUND: Cushing's Syndrome (CS) which is caused by isolated corticotropin
      releasing hormone (CRH) production, rather than adrenocorticotropin (ACTH)
      production, is extremely rare. METHODS: We describe the clinical presentation,
      course, laboratory values and pathologic findings of a patient with isolated
      ectopic CRH causing CS. We review the literature of the types of tumors
      associated with this unusual syndrome and the behavior of these tumors by
      endocrine testing. RESULTS: A 56 year old woman presented with clinical and
      laboratory features consistent with ACTH-dependent CS. Pituitary imaging was
      normal and cortisol did not suppress with a high dose dexamethasone test,
      consistent with a diagnosis of ectopic ACTH. CT imaging did not reveal any
      discrete lung lesions but there were mediastinal and abdominal lymphadenopathy
      and multiple liver lesions suspicious for metastatic disease. Laboratory testing
      was positive for elevated serum carcinoembryonic antigen and the neuroendocrine
      marker chromogranin A. Serum markers of carcinoid, medullary thyroid carcinoma,
      and pheochromocytoma were in the normal range. Because the primary tumor could
      not be identified by imaging, biopsy of the presumed metastatic liver lesions was
      performed. Immunohistochemistry was consistent with a neuroendocrine tumor,
      specifically small cell carcinoma. Immunostaining for ACTH was negative but was
      strongly positive for CRH and laboratory testing revealed a plasma CRH of 10
      pg/ml (normal 0 to 10 pg/ml) which should have been suppressed in the presence of
      high cortisol. CONCLUSIONS: This case illustrates the importance of considering
      the ectopic production of CRH in the differential diagnosis for presentations of
      ACTH-dependent Cushing's Syndrome.

PMID- 20807419
TI  - Phylogenetic relationships and biogeographical patterns in Circum-Mediterranean
      subfamily Leuciscinae (Teleostei, Cyprinidae) inferred from both mitochondrial
      and nuclear data.
AB  - BACKGROUND: Leuciscinae is a subfamily belonging to the Cyprinidae fish family
      that is widely distributed in Circum-Mediterranean region. Many efforts have been
      carried out to deciphering the evolutionary history of this group. Thus,
      different biogeographical scenarios have tried to explain the colonization of
      Europe and Mediterranean area by cyprinids, such as the "north dispersal" or the
      "Lago Mare dispersal" models. Most recently, Pleistocene glaciations influenced
      the distribution of leuciscins, especially in North and Central Europe. Weighing
      up these biogeographical scenarios, this paper constitutes not only the first
      attempt at deciphering the mitochondrial and nuclear relationships of
      Mediterranean leuciscins but also a test of biogeographical hypotheses that could
      have determined the current distribution of Circum-Mediterranean leuciscins.
      RESULTS: A total of 4439 characters (mitochondrial + nuclear) from 321
      individuals of 176 leuciscine species rendered a well-supported phylogeny,
      showing fourteen main lineages. Analyses of independent mitochondrial and nuclear
      markers supported the same main lineages, but basal relationships were not
      concordant. Moreover, some incongruence was found among independent mitochondrial
      and nuclear phylogenies. The monophyly of some poorly known genera such as
      Pseudophoxinus and Petroleuciscus was rejected. Representatives of both genera
      belong to different evolutionary lineages. Timing of cladogenetic events among
      the main leuciscine lineages was gained using mitochondrial and all genes data
      set. CONCLUSIONS: Adaptations to a predatory lifestyle or miniaturization have
      superimposed the morphology of some species. These species have been separated
      into different genera, which are not supported by a phylogenetic framework. Such
      is the case of the genera Pseudophoxinus and Petroleuciscus, which real taxonomy
      is not well known. The diversification of leuciscine lineages has been determined
      by intense vicariant events following the paleoclimatological and hydrogeological
      history of Mediterranean region. We propose different colonization models of
      Mediterranean region during the early Oligocene. Later vicariance events promoted
      Leuciscinae diversification during Oligocene and Miocene periods. Our data
      corroborate the presence of leuciscins in North Africa before the Messinian
      salinity crisis. Indeed, Messinian period appears as a stage of gradually
      Leuciscinae diversification. The rise of humidity at the beginning of the
      Pliocene promoted the colonization and posterior isolation of newly established
      freshwater populations. Finally, Pleistocene glaciations determined the current
      European distribution of some leuciscine species.

PMID- 20807420
TI  - Teamwork skills, shared mental models, and performance in simulated trauma teams:
      an independent group design.
AB  - BACKGROUND: Non-technical skills are seen as an important contributor to reducing
      adverse events and improving medical management in healthcare teams. Previous
      research on the effectiveness of teams has suggested that shared mental models
      facilitate coordination and team performance. The purpose of the study was to
      investigate whether demonstrated teamwork skills and behaviour indicating shared
      mental models would be associated with observed improved medical management in
      trauma team simulations. METHODS: Revised versions of the 'Anesthetists' Non
      Technical Skills Behavioural marker system' and 'Anti-Air Teamwork Observation
      Measure' were field tested in moment-to-moment observation of 27 trauma team
      simulations in Norwegian hospitals. Independent subject matter experts rated
      medical management in the teams. An independent group design was used to explore
      differences in teamwork skills between higher-performing and lower-performing
      teams. RESULTS: Specific teamwork skills and behavioural markers were associated
      with indicators of good team performance. Higher and lower-performing teams
      differed in information exchange, supporting behaviour and communication, with
      higher performing teams showing more effective information exchange and
      communication, and less supporting behaviours. Behavioural markers of shared
      mental models predicted effective medical management better than teamwork skills.
      CONCLUSIONS: The present study replicates and extends previous research by
      providing new empirical evidence of the significance of specific teamwork skills
      and a shared mental model for the effective medical management of trauma teams.
      In addition, the study underlines the generic nature of teamwork skills by
      demonstrating their transferability from different clinical simulations like the
      anaesthesia environment to trauma care, as well as the potential usefulness of
      behavioural frequency analysis in future research on non-technical skills.

PMID- 20807422
TI  - Population attributable fraction: comparison of two mathematical procedures to
      estimate the annual attributable number of deaths.
AB  - OBJECTIVE: The purpose of this paper was to compare two mathematical procedures
      to estimate the annual attributable number of deaths (the Allison et al procedure
      and the Mokdad et al procedure), and derive a new procedure that combines the
      best aspects of both procedures. The new procedure calculates attributable number
      of deaths along a continuum (i.e. for each unit of exposure), and allows for one
      or more neutral (neither exposed nor nonexposed) exposure categories. METHODS:
      Mathematical derivations and real datasets were used to demonstrate the
      theoretical relationship and practical differences between the two procedures.
      Results of the comparison were used to develop a new procedure that combines the
      best features of both. FINDINGS: The Allison procedure is complex because it
      directly estimates the number of attributable deaths. This necessitates
      calculation of probabilities of death. The Mokdad procedure is simpler because it
      estimates the number of attributable deaths indirectly through population
      attributable fractions. The probabilities of death cancel out in the numerator
      and denominator of the fractions. However, the Mokdad procedure is not applicable
      when a neutral exposure category exists. CONCLUSION: By combining the innovation
      of the Allison procedure (allowing for a neutral category) and the simplicity of
      the Mokdad procedure (using population attributable fractions), this paper
      proposes a new procedure to calculate attributable numbers of death.

PMID- 20807421
TI  - Perceptions of immunization information systems for collecting pandemic H1N1
      immunization data within Canada's public health community: a qualitative study.
AB  - BACKGROUND: Immunization information systems (IISs) are electronic registries
      used to monitor individual vaccination status and assess vaccine coverage. IISs
      are currently not widely used across Canada, where health jurisdictions employ a
      range of approaches to capture influenza immunization information. Conducted in
      advance of the 2009 H1N1 vaccination campaign, the objectives of this study were
      to understand the perceived value of individual-level data and IISs for influenza
      control, identify ideal system functions, and explore barriers to implementation.
      METHODS: In July and August 2009, semi-structured interviews were conducted with
      key informants engaged in vaccine delivery and/or pandemic planning at regional,
      provincial/territorial and federal levels across Canada. Key informants were
      recruited using a combination of convenience and snowball sampling methodologies.
      Qualitative analysis was used to extract themes from interview content. RESULTS:
      Patient management, assessment of vaccine coverage, and evaluation of safety and
      effectiveness were identified as public health priorities that would be achieved
      in a more timely manner, and with greater accuracy, through the use of an IIS.
      Features described as ideal included system flexibility, rapid data entry, and
      universality. Financial and human resource constraints as well as coordination
      between immunization providers were expressed as barriers to implementation.
      CONCLUSIONS: IISs were perceived as valuable by key informants for strengthening
      management capacity and improving evaluation of both seasonal and pandemic
      influenza vaccination campaigns. However, certain implementation restrictions may
      need to be overcome for these benefits to be achieved.

PMID- 20807423
TI  - Two storage hexamerins from the beet armyworm Spodoptera exigua: cloning,
      characterization and the effect of gene silencing on survival.
AB  - BACKGROUND: In insects, hemocyanin superfamily proteins accumulate apparently to
      serve as sources of amino acids during metamorphosis, reproduction and
      development. Storage hexamerins are important members of the hemocyanin
      superfamily. Although insects possess storage hexamerins, very little is known
      about the character and specific functions of hexamerin 1 and storage protein 1
      in insect development. RESULTS: To gain insight into the function of storage
      proteins in insects, cDNAs for two storage proteins were cloned from the fat body
      of Spodoptera exigua. S. exigua hexamerin 1 (SeHex) cDNA contained an open
      reading frame of 2124 nucleotides encoding a protein of 707 amino acids with a
      predicted molecular weight of 82.12 kDa. S. exigua storage protein 1 (SeSP1) cDNA
      contained an open reading frame of 2256 bp encoding a protein of 751 amino acids
      with a predicted molecular weight of ~88.84 kDa. Northern blotting analyses
      revealed that SeHex mRNA is expressed in the fat body, cuticle, midgut and
      Malpighian tubules and SeSP1 in fat body, Malpighian tubules and tracheae. SeHex
      and SeSP1 mRNAs were expressed in fat body at different levels from first instar
      larvae to pupae, with expression was much lower from first instar larvae to first
      day fifth instar larvae. SeHex transcript expression was high in fat body of
      wandering larvae (pre-pupae) and steadily decreased to the seventh pupal day.
      SeSP1 transcript expression was high in fat body of wandering larvae, 2-day-old
      fifth instar larvae and 2-, 4- and 7-day-old pupae. SeHex and SeSP1 mRNAs levels
      were expressed lower than control on the condition of starvation at 12 h. Of
      insects injected with SeHex and SeSP1 dsRNA, 38.7% and 24.3% survived to 204 h
      after treatment, respectively. This was significantly lower than in the controls
      groups. CONCLUSIONS: These findings provide new data on the tissue distribution,
      expression patterns and the function in starvation of storage proteins. RNA
      interference results revealed that storage protein genes are key in
      metamorphosis, reproduction and insect development. The results for SeHex and
      SeSP1 interference reveal that a potential method to control this pest is to
      disrupt the regulation of storage proteins.

PMID- 20807424
TI  - Laryngeal Mask Airway for neonatal resuscitation in a developing country:
      evaluation of an educational intervention. Neonatal LMA: an educational
      intervention in DRC.
AB  - BACKGROUND: Studies carried out in developing countries have indicated that
      training courses in newborn resuscitation are efficacious in teaching local birth
      attendants how to properly utilize simple resuscitation devices. The aim of this
      study was to assess the knowledge and expertise gained by physicians and midwifes
      who participated in a Neonatal Resuscitation Course and workshop organized in a
      Third World Country on the use of Laryngeal Mask Airway (LMA). METHODS: A 28-item
      questionnaire, derived from the standard test contained in the American Heart
      Association and the American Academy of Pediatrics Neonatal Resuscitation Manual,
      was administered to 21 physicians and 7 midwifes before and after a course, which
      included a practical, hands-on workshop focusing on LMA positioning and bag
      ventilation in a neonatal manikin. RESULTS: The knowledge gained by the
      physicians was superior to that demonstrated by the midwifes. The physicians, in
      fact, demonstrated a significant improvement with respect to their pre-course
      knowledge. Both the physicians and the midwives showed a good level of expertise
      in manipulating the manipulating the manikin during the practical trial session.
      The midwifes and physicians almost unanimously manifested a high degree of
      approval of neonatal resuscitation by LMA, as they defined it a sustainable and
      cost-effective method requiring minimal expertise. CONCLUSIONS: Further studies
      are warranted to test the advantages and limits of the neonatal LMA training
      courses in developing countries.

PMID- 20807425
TI  - There is (still) too much aluminium in infant formulas.
AB  - BACKGROUND: Infant formulas are sophisticated milk-based feeds for infants which
      are used as a substitute for breast milk. Historically they are known to be
      contaminated by aluminium and in the past this has raised health concerns for
      exposed infants. We have measured the aluminium content of a number of widely
      used infant formulas to determine if their contamination by aluminium and
      consequent issues of child health persists. METHODS: Samples of ready-made milks
      and powders used to make milks were prepared by microwave digestion of
      acid/peroxide mixtures and their aluminium content determined by THGA. RESULTS:
      The concentration of aluminium in ready-made milks varied from ca 176 to 700
      MUg/L. The latter concentration was for a milk for preterm infants. The aluminium
      content of powders used to make milks varied from ca 2.4 to 4.3 MUg/g. The latter
      content was for a soya-based formula and equated to a ready-to-drink milk
      concentration of 629 MUg/L. Using the manufacturer's own guidelines of formula
      consumption the average daily ingestion of aluminium from infant formulas for a
      child of 6 months varied from ca 200 to 600 MUg of aluminium. Generally ingestion
      was higher from powdered as compared to ready-made formulas. CONCLUSIONS: The
      aluminium content of a range of well known brands of infant formulas remains high
      and particularly so for a product designed for preterm infants and a soya-based
      product designed for infants with cow's milk intolerances and allergies. Recent
      research demonstrating the vulnerability of infants to early exposure to
      aluminium serves to highlight an urgent need to reduce the aluminium content of
      infant formulas to as low a level as is practically possible.

PMID- 20807426
TI  - Commitment of chondrogenic precursors of the avian scapula takes place after
      epithelial-mesenchymal transition of the dermomyotome.
AB  - BACKGROUND: Cells of the epithelially organised dermomyotome are traditionally
      believed to give rise to skeletal muscle and dermis. We have previously shown
      that the dermomyotome can undergo epithelial-mesenchymal transition (EMT) and
      give rise to chondrogenic cells, which go on to form the scapula blade in birds.
      At present we have little understanding regarding the issue of when the
      chondrogenic fate of dermomyotomal cells is determined. Using quail-chick
      grafting experiments, we investigated whether scapula precursor cells are
      committed to a chondrogenic fate while in an epithelial state or whether
      commitment is established after EMT. RESULTS: We show that the hypaxial
      dermomyotome, which normally forms the scapula, does not generate cartilaginous
      tissue after it is grafted to the epaxial domain. In contrast engraftment of the
      epaxial dermomyotome to the hypaxial domain gives rise to scapula-like cartilage.
      However, the hypaxial sub-ectodermal mesenchyme (SEM), which originates from the
      hypaxial dermomyotome after EMT, generates cartilaginous elements in the epaxial
      domain, whereas in reciprocal grafting experiments, the epaxial SEM cannot form
      cartilage in the hypaxial domain. CONCLUSIONS: We suggest that the epithelial
      cells of the dermomyotome are not committed to the chondrogenic lineage.
      Commitment to this lineage occurs after it has undergone EMT to form the sub
      ectodermal mesenchyme.

PMID- 20807427
TI  - Brain herniation in a patient with apparently normal intracranial pressure: a
      case report.
AB  - INTRODUCTION: Intracranial pressure monitoring is commonly implemented in
      patients with neurologic injury and at high risk of developing intracranial
      hypertension, to detect changes in intracranial pressure in a timely manner. This
      enables early and potentially life-saving treatment of intracranial hypertension.
      CASE PRESENTATION: An intraparenchymal pressure probe was placed in the
      hemisphere contralateral to a large basal ganglia hemorrhage in a 75-year-old
      Caucasian man who was mechanically ventilated and sedated because of depressed
      consciousness. Intracranial pressures were continuously recorded and never
      exceeded 17 mmHg. After sedation had been stopped, our patient showed clinical
      signs of transtentorial brain herniation, despite apparently normal intracranial
      pressures (less than 10 mmHg). Computed tomography revealed that the size of the
      intracerebral hematoma had increased together with significant unilateral brain
      edema and transtentorial herniation. The contralateral hemisphere where the
      intraparenchymal pressure probe was placed appeared normal. Our patient underwent
      emergency decompressive craniotomy and was tracheotomized early, but did not
      completely recover. CONCLUSIONS: Intraparenchymal pressure probes placed in the
      hemisphere contralateral to an intracerebral hematoma may dramatically
      underestimate intracranial pressure despite apparently normal values, even in the
      case of transtentorial brain herniation.

PMID- 20807428
TI  - Possible role of alpha-lipoic acid in the treatment of peripheral nerve injuries.
AB  - Recent findings on the antioxidant effects of pretreatment with alpha-lipoic
      acid (alpha-LA) on the crush injury of rat sciatic nerve confirm the possible
      usefulness of alpha-LA administration in humans with peripheral nerve injuries.
      We discussed this issue in relation with our recent results in which the combined
      employment of alpha-LA and gamma-linolenic acid with a rehabilitation program for
      six weeks reduced sensory symptoms and neuropathic pain in patients with
      compressive radiculopathy syndrome from disc-nerve root conflict in comparison
      with patients submitted to rehabilitation program alone for six weeks.

PMID- 20807430
TI  - Feasibility of breast conservation after neoadjuvant taxene based chemotherapy in
      locally advanced breast cancer: a Prospective Phase I trial.
AB  - BACKGROUND: Neoadjuvant chemotherapy is the standard care for locally advanced
      breast cancer. Our study aimed at evaluating the feasibility of breast
      conversation surgery (BCS) after neoadjuvant chemotherapy. PATIENTS AND METHODS:
      Forty five patients had stage IIB (except those with T2N1 disease) and stage IIIA
      were selected to 3 cycles taxane-based neoadjuvant chemotherapy. Patient who had
      tumours <=5 cm underwent a tentative BCS while patients who had tumour size >5 cm
      underwent radical surgery. Negative margin is essential for BCS. Adjuvant
      chemotherapy and 3-D radiotherapy +/- hormonal treatment were given to all
      patients. RESULTS: Thirty four patients had BCS. Response to chemotherapy was the
      only statistically significant factor which influences the BCS. Incidence of
      local recurrence was 5.9% for patients who had BCS at a median follow up 24
      months. CONCLUSION: Breast conservation is feasible in selected cases of locally
      advanced, non metastatic cancer breast. We recommend that patients who have
      tumour size <=4 cm after chemotherapy are the best candidates for BCS.

PMID- 20807429
TI  - Nutrition, mental health and violence: from pregnancy to postpartum Cohort of
      women attending primary care units in Southern Brazil--ECCAGE study.
AB  - BACKGROUND: Woman's nutritional status, before and during pregnancy, is a strong
      determinant of health outcomes in the mother and newborn. Gestational weight gain
      and postpartum weight retention increases risk of overweight or obesity in the
      future and they depend on the pregestational nutritional status and on food
      consumption and eating behavior during pregnancy. Eating behavior during
      pregnancy may be the cause or consequence of mood changes during pregnancy,
      especially depression, which increases likelihood of postpartum depression. In
      Brazil, a study carried out in the immediate postpartum period found that one in
      three women experienced some type of violence during pregnancy. Violence and
      depression are strongly associated and both exposures during pregnancy are
      associated with increased maternal stress and subsequent harm to the infant. The
      main objectives of this study are: to identify food intake and eating behaviors
      patterns; to estimate the prevalence of common mental disorders and the
      experience of violence during and after pregnancy; and to estimate the
      association between these exposures and infant's health and development.
      METHODS/DESIGN: This is a cohort study of 780 pregnant women receiving care in 18
      primary care units in two cities in Southern Brazil. Pregnant women were first
      evaluated between the 16th and 36th week of pregnancy at a prenatal visit. Follow
      up included immediate postpartum assessment and around the fifth month
      postpartum. Information was obtained on sociodemographic characteristics, living
      circumstances, food intake, eating behaviors, mental health and exposure to
      violence, and on infant's development and anthropometrics measurements.
      DISCUSSION: This project will bring relevant information for a better
      understanding of the relationship between exposures during pregnancy and how they
      might affect child development, which can be useful for a better planning of
      health actions aiming to enhance available resources in primary health care.

PMID- 20807431
TI  - Susceptibility of the human retrovirus XMRV to antiretroviral inhibitors.
AB  - BACKGROUND: XMRV (xenotropic murine leukemia virus-related virus) is the first
      known example of an exogenous gammaretrovirus that can infect humans. A limited
      number of reports suggest that XMRV is intrinsically resistant to many of the
      antiretroviral drugs used to treat HIV-1 infection, but is sensitive to a small
      subset of these inhibitors. In the present study, we used a novel marker transfer
      assay to directly compare the antiviral drug sensitivities of XMRV and HIV-1
      under identical conditions in the same host cell type. RESULTS: We extend the
      findings of previous studies by showing that, in addition to AZT and tenofovir,
      XMRV and HIV-1 are equally sensitive to AZddA (3'-azido-2',3'-dideoxyadenosine),
      AZddG (3'-azido-2',3'-dideoxyguanosine) and adefovir. These results indicate that
      specific 3'-azido or acyclic nucleoside analog inhibitors of HIV-1 reverse
      transcriptase (RT) also block XMRV infection with comparable efficacy in vitro.
      Our data confirm that XMRV is highly resistant to the non-nucleoside RT
      inhibitors nevirapine and efavirenz and to inhibitors of HIV-1 protease. In
      addition, we show that the integrase inhibitors raltegravir and elvitegravir are
      active against XMRV, with EC50 values in the nanomolar range. CONCLUSIONS: Our
      analysis demonstrates that XMRV exhibits a distinct pattern of nucleoside analog
      susceptibility that correlates with the structure of the pseudosugar moiety and
      that XMRV is sensitive to a broader range of antiretroviral drugs than has
      previously been reported. We suggest that the divergent drug sensitivity profiles
      of XMRV and HIV-1 are partially explained by specific amino acid differences in
      their respective protease, RT and integrase sequences. Our data provide a basis
      for choosing specific antiretroviral drugs for clinical studies in XMRV-infected
      patients.

PMID- 20807432
TI  - Services used by perinatal substance-users with child welfare involvement: a
      descriptive study.
AB  - BACKGROUND: Substance use during pregnancy often leads to involvement in the
      child welfare system, resulting in multiple social service systems and service
      providers working with families to achieve successful child welfare outcomes. The
      Vulnerable Infants Program of Rhode Island (VIP-RI) is a care coordination
      program developed to work with perinatal substance-users to optimize
      opportunities for reunification and promote permanency for substance-exposed
      infants. This paper describes services used by VIP-RI participants and child
      welfare outcomes. METHODS: Data collected during the first four years of VIP-RI
      were used to identify characteristics of program participants, services received,
      and child welfare outcomes: closed child welfare cases, reunification with
      biological mothers and identified infant permanent placements. DESCRIPTIVE
      RESULTS: Medical and financial services were associated with positive child
      welfare outcomes. Medical services included family planning, pre- and post-natal
      care and HIV test counseling. Financial services included assistance with
      obtaining entitlement benefits and receiving tangible support such as food and
      clothing. CONCLUSIONS: Findings from this study suggest services that address
      basic family needs were related to positive child welfare outcomes. The provision
      of basic services, such as health care and financial assistance through
      entitlement benefits and tangible donations, may help to establish a foundation
      so mothers can concentrate on recovery and parenting skills. Identification of
      services for perinatal substance users that are associated with more successful
      child welfare outcomes has implications for the child welfare system, treatment
      providers, courts and families.

PMID- 20807433
TI  - The essential role of bursicon during Drosophila development.
AB  - BACKGROUND: The protective external cuticle of insects does not accommodate
      growth during development. To compensate for this, the insect life cycle is
      punctuated by a series of molts. During the molt, a new and larger cuticle is
      produced underneath the old cuticle. Replacement of the smaller, old cuticle
      culminates with ecdysis, a stereotyped sequence of shedding behaviors. Following
      each ecdysis, the new cuticle must expand and harden. Studies from a variety of
      insect species indicate that this cuticle hardening is regulated by the
      neuropeptide bursicon. However, genetic evidence from Drosophila melanogaster
      only supports such a role for bursicon after the final ecdysis, when the adult
      fly emerges. The research presented here investigates the role that bursicon has
      at stages of Drosophila development which precede adult ecdysis. RESULTS: We
      addressed the mechanism and timing of hormonal release from bursicon-positive
      motor neurons at the larval neuromuscular junction. Our findings indicate that
      vesicle membrane proteins which are required for classical neurotransmitter
      release are also expressed at these peptidergic motor neuron terminals; and that
      these terminals secrete hormones including bursicon at the neuromuscular
      junction, coinciding with larval ecdysis. This release surprisingly occurs in two
      waves, indicating bursicon secretion preceding and following the ecdysis
      sequence. Next, we addressed the functional significance of bursicon signaling
      during development, by disrupting the expression of its receptor, rickets, in
      different target tissues. We determined that rickets is developmentally required
      in the epidermis and imaginal discs for proper formation of the prepupa. It is
      also required to harden the pharate adult cuticle before eclosion. Significantly,
      we have also found that the available rickets mutants are not genetic nulls as
      previously believed, which necessitated the use of targeted RNA interference to
      disrupt rickets expression. CONCLUSIONS: Our results are consistent with the view
      that bursicon is the insect tanning hormone. However, this is the first study to
      rigorously demonstrate both its release and function during development.
      Importantly, we provide new evidence that bursicon release can precede the
      initiation of larval ecdysis, and that bursicon tans the puparium. Our results
      firmly establish bursicon signaling as essential to insect growth and
      development.

PMID- 20807434
TI  - "The lobbying strategy is to keep excise as low as possible" - tobacco industry
      excise taxation policy in Ukraine.
AB  - BACKGROUND: Tobacco taxes are one of the most effective ways to reduce tobacco
      use. Transnational tobacco companies (TTCs) claim they wish to develop and secure
      excise systems that benefit both governments and the profitability of the
      companies themselves. The objective of the paper is to use the case of Ukraine,
      with its inconsistent history of excise tax changes in 1992-2008, to explore
      tobacco industry taxation strategies and tactics, and their implications for
      governmental revenues. METHODS: Details of tobacco industry policy on tobacco
      taxation in Ukraine were obtained by searching tobacco industry internal
      documents and various published reports. RESULTS: Even before entering the market
      in Ukraine, TTCs had made efforts to change the excise system in the country. In
      1993-1994, TTCs lobbied the Ukrainian Government, and succeeded in achieving a
      lowering in tobacco tax. This, however, did not produce revenue increase they
      promised the Government. In 1996-1998, Ukrainian authorities increased excise
      several times, ignoring the wishes of TTCs, caused significant growth in revenue.
      Due to TTCs lobbying activities in 1999-2007 the tax increases were very moderate
      and it resulted in increased tobacco consumption in Ukraine. In 2008, despite the
      TTCs position, excise rates were increased twice and it was very beneficial for
      revenues. CONCLUSIONS: The Framework Convention on Tobacco Control includes
      provisions both on tobacco taxation policy and on protection of public health
      policy from vested interests of tobacco industry. This paper provides arguments
      why tobacco taxation policy should also be protected from vested interests of
      tobacco industry. TTCs taxation strategy appears to be consistent: keep excise as
      low as possible. Apparent conflicts between TTCs concerning tax structures often
      hide their real aim to change tax structures for competing interests without
      increasing total tax incidence. Governments, that aim to reduce levels of tobacco
      use, should not allow tobacco companies to influence the development and
      implementation of tobacco taxation policy.

PMID- 20807435
TI  - Development and testing of the BONES physical activity survey for young children.
AB  - BACKGROUND: Weight-bearing and high intensity physical activities are
      particularly beneficial for stimulating bone growth in children given that bone
      responds favorably to mechanical load. While it is important to assess the
      contribution and impact of weight-bearing physical activity on health outcomes,
      measurement tools that quantify and provide information on these activities
      separately from overall physical activity are limited. This study describes the
      development and evaluation of a pictorial physical activity survey (PAS) that
      measures children's participation and knowledge of high-intensity, weight-bearing
      ("bone smart") physical activity. METHODS: To test reliability, two identical
      sets of the PAS were administered on the same day to 41 children (mean age 7.1 +/
      0.8 years; 63% female) and compared. To test validity, accelerometry data from
      40 children (mean age 7.7 +/- 0.8 years; 50% female) were compared to data
      provided by the PAS. Agreements between categorical and ordinal items were
      assessed with Kappa statistics; agreements between continuous indices were
      assessed with Spearman's correlation tests. RESULTS: The subjects produced
      reliable results in all 10 physical activity participation items (kappa range:
      0.36-0.73, all p < 0.05), but less reliable in answering if the physical
      activities were "bone smart" (kappa range: -0.04-0.66). Physical activity
      indices, including metabolic equivalent time and weight-bearing factors, were
      significant in test-retest analyses (Spearman's r range: 0.57-0.74, all p <
      0.001). Minutes of very vigorous activity from the accelerometer were associated
      with the self-reported weight-bearing activity, moderate-high, and high activity
      scores from the PAS (Spearman's r range: 0.47-0.48, all p < 0.01). However,
      accelerometer counts, counts per minute, and minutes of moderate-vigorous and
      vigorous activity were not associated with the PAS scores. CONCLUSIONS: Together,
      the results of these studies suggest that the PAS has acceptable test-retest
      reliability, but limited validity for early elementary school children. This
      survey demonstrates a first step towards developing a questionnaire that measures
      high intensity, weight-bearing activity in schoolchildren.

PMID- 20807436
TI  - Collaborative development of predictive toxicology applications.
AB  - OpenTox provides an interoperable, standards-based Framework for the support of
      predictive toxicology data management, algorithms, modelling, validation and
      reporting. It is relevant to satisfying the chemical safety assessment
      requirements of the REACH legislation as it supports access to experimental data,
      (Quantitative) Structure-Activity Relationship models, and toxicological
      information through an integrating platform that adheres to regulatory
      requirements and OECD validation principles. Initial research defined the
      essential components of the Framework including the approach to data access,
      schema and management, use of controlled vocabularies and ontologies,
      architecture, web service and communications protocols, and selection and
      integration of algorithms for predictive modelling. OpenTox provides end-user
      oriented tools to non-computational specialists, risk assessors, and
      toxicological experts in addition to Application Programming Interfaces (APIs)
      for developers of new applications. OpenTox actively supports public standards
      for data representation, interfaces, vocabularies and ontologies, Open Source
      approaches to core platform components, and community-based collaboration
      approaches, so as to progress system interoperability goals.The OpenTox Framework
      includes APIs and services for compounds, datasets, features, algorithms, models,
      ontologies, tasks, validation, and reporting which may be combined into multiple
      applications satisfying a variety of different user needs. OpenTox applications
      are based on a set of distributed, interoperable OpenTox API-compliant REST web
      services. The OpenTox approach to ontology allows for efficient mapping of
      complementary data coming from different datasets into a unifying structure
      having a shared terminology and representation.Two initial OpenTox applications
      are presented as an illustration of the potential impact of OpenTox for high
      quality and consistent structure-activity relationship modelling of REACH
      relevant endpoints: ToxPredict which predicts and reports on toxicities for
      endpoints for an input chemical structure, and ToxCreate which builds and
      validates a predictive toxicity model based on an input toxicology dataset.
      Because of the extensible nature of the standardised Framework design, barriers
      of interoperability between applications and content are removed, as the user may
      combine data, models and validation from multiple sources in a dependable and
      time-effective way.

PMID- 20807438
TI  - Relations as patterns: bridging the gap between OBO and OWL.
AB  - BACKGROUND: most biomedical ontologies are represented in the OBO Flatfile
      Format, which is an easy-to-use graph-based ontology language. The semantics of
      the OBO Flatfile Format 1.2 enforces a strict predetermined interpretation of
      relationship statements between classes. It does not allow flexible
      specifications that provide better approximations of the intuitive understanding
      of the considered relations. If relations cannot be accurately expressed then
      ontologies built upon them may contain false assertions and hence lead to false
      inferences. Ontologies in the OBO Foundry must formalize the semantics of
      relations according to the OBO Relationship Ontology (RO). Therefore, being able
      to accurately express the intended meaning of relations is of crucial importance.
      Since the Web Ontology Language (OWL) is an expressive language with a formal
      semantics, it is suitable to de ne the meaning of relations accurately. RESULTS:
      we developed a method to provide definition patterns for relations between
      classes using OWL and describe a novel implementation of the RO based on this
      method. We implemented our extension in software that converts ontologies in the
      OBO Flatfile Format to OWL, and also provide a prototype to extract relational
      patterns from OWL ontologies using automated reasoning. The conversion software
      is freely available at http://bioonto.de/obo2owl, and can be accessed via a web
      interface. CONCLUSIONS: explicitly defining relations permits their use in
      reasoning software and leads to a more flexible and powerful way of representing
      biomedical ontologies. Using the extended langua0067e and semantics avoids
      several mistakes commonly made in formalizing biomedical ontologies, and can be
      used to automatically detect inconsistencies. The use of our method enables the
      use of graph-based ontologies in OWL, and makes complex OWL ontologies accessible
      in a graph-based form. Thereby, our method provides the means to gradually move
      the representation of biomedical ontologies into formal knowledge representation
      languages that incorporates an explicit semantics. Our method facilitates the use
      of OWL-based software in the back-end while ontology curators may continue to
      develop ontologies with an OBO-style front-end.

PMID- 20807437
TI  - EGF regulates survivin stability through the Raf-1/ERK pathway in insulin
      secreting pancreatic beta-cells.
AB  - BACKGROUND: Postnatal expansion of the pancreatic beta-cell mass is required to
      maintain glucose homeostasis immediately after birth. This beta-cell expansion is
      regulated by multiple growth factors, including glucose, insulin, insulin-like
      growth factor (IGF-1) and epidermal growth factor (EGF). These mitogens signal
      through several downstream pathways (AKT, ERK, STAT3, and JNK) to regulate the
      survival and proliferation of beta-cells. Survivin, an oncofetal protein with
      both pro-proliferative and anti-apoptotic properties, is a known transcriptional
      target of both IGF-1 and EGF in cancer cells. Here, we analyzed the effects of
      the beta-cell mitogens IGF-1 and EGF on survivin regulation in the established
      pancreatic beta-cell model cell lines, MIN6 and INS-1 and in primary mouse
      islets. RESULTS: In pancreatic beta-cells, treatment with glucose, insulin, or
      EGF increased survivin protein levels at early time points. By contrast, no
      significant effects on survivin were observed following IGF-1 treatment. EGF
      stimulated increases in survivin protein were abrogated in the presence of
      downstream inhibitors of the Raf-1/MEK/ERK pathway. EGF had no significant effect
      on survivin transcription however it prolonged the half-life of the survivin
      protein and stabilized survivin protein levels by inhibiting surviving
      ubiquitination. CONCLUSIONS: This study defines a novel mechanism of survivin
      regulation by EGF through the Raf-1/MEK/ERK pathway in pancreatic beta-cells, via
      prolongation of survivin protein half-life and inhibition of the ubiquitin
      mediated proteasomal degradation pathway. This mechanism may be important for
      regulating beta-cell expansion after birth.

PMID- 20807439
TI  - Increased susceptibility to cardiovascular effects of dihydrocapcaicin in
      resuscitated rats. Cardiovascular effects of dihydrocapsaicin.
AB  - BACKGROUND: Survivors of a cardiac arrest often have persistent cardiovascular
      derangements following cardiopulmonary resuscitation including decreased cardiac
      output, arrhythmias and morphological myocardial damage. These cardiovascular
      derangements may lead to an increased susceptibility towards the external and
      internal environment of the cardiovascular system as compared to the healthy
      situation. METHODS: Here we tested the hypothesis that the cardiovascular system
      in healthy rats and rats resuscitated from a cardiac arrest may be differentially
      affected by a transient receptor potential vanilloid type 1 agonist, by
      continuous intravenous infusion of dihydrocapsaicin (DHC). RESULTS: Compared to
      baseline, infusion of DHC caused an initial increase in mean arterial blood
      pressure in both healthy and resuscitated rats of 25% and 10%, respectively.
      Also, we observed an initial response of tachycardia in both healthy and
      resuscitated rats of 30% and 20%, respectively. Then, at high levels of DHC
      infusion (> 2.0 mg/kg/hr) we observed two single episodes of transient
      bradycardia and hypotension in 33% of the healthy rats, which was consistent with
      a TRPV1 agonist induced Bezold-Jarisch reflex. In contrast, in resuscitated rats
      we observed multiple episodes of bradycardia/hypotension in 100% of the rats and
      at a dose of DHC of 0.65 mg/kg/hr. Notably, this DHC effect could be completely
      blocked in the resuscitated rats by pre-treatment with atropine, a muscarinic
      acetylcholine antagonist. CONCLUSIONS: Our results indicate that the
      susceptibility of the rats towards TRPV1 agonist induced Bezold-Jarisch reflex is
      increased in those resuscitated from cardiac arrest compared to the healthy
      situation.

PMID- 20807440
TI  - Behavior of a viscoelastic valveless pump: a simple theory with experimental
      validation.
AB  - BACKGROUND: A valveless pump generates a unidirectional net flow of fluid around
      a closed loop of soft viscoelastic tubing that is rhythmically compressed at one
      point. The tubing must have at least two sections with two different stiffnesses.
      When a short segment of the tube is squeezed asymmetrically at certain
      frequencies, net flow of fluid around the loop can occur without valves. METHODS:
      Partial differential equations for the pressures, volumes, and flows define a
      simple one-dimensional model of such a pump, based upon elementary physical
      principles. Numerical computations on a personal computer can predict measured
      net flows. RESULTS: Net flow varies with the frequency and waveform of
      compression used to excite the pump, as well as with the site of compression and
      the stiffness and viscosity of the tubing. Net flows on the order of 1 ml/sec are
      obtained in a water-filled loop including 46 cm of stiffer plastic (Tygon)
      laboratory tubing and 70 cm of softer latex rubber tubing. CONCLUSIONS: The
      heretofore mysterious phenomenon of valveless pumping can be described in terms
      of classical Newtonian physics, in which viscous damping in the walls of the pump
      is included. Studying valveless pumps in the laboratory and modeling their
      behavior numerically provides a low-cost, engaging, and instructive exercise for
      research and teaching in biomedical engineering.

PMID- 20807441
TI  - Patient understanding of moles and skin cancer, and factors influencing
      presentation in primary care: a qualitative study.
AB  - BACKGROUND: Melanoma incidence in the UK has doubled over two decades, yet there
      is conflicting evidence about factors which prompt or delay patients seeking
      advice. AIM: To explore patient understanding of pigmented skin lesions (moles)
      and skin cancer, and factors which influence seeking help in primary care.
      METHOD: Semi-structured interviews with forty MoleMate Trial participants,
      analysed using the theoretical framework of the Safer-Andersen model of Total
      Patient Delay. RESULTS: Patient understanding and awareness was influenced by
      personal, family and friends' experiences of moles, skin cancer and other
      cancers, knowledge of risk factors, and the lay media. The route to consulting
      was complex and often iterative. For lesions that people could see, detecting and
      appraising change was influenced by comparisons with a normal mole on themselves,
      a family member, friend or image. Inferring illness came about with recognition
      of changes (particularly size) as serious, and associated 'internal' symptoms
      such as pain. For lesions that people could not see, family, friends and health
      professionals detected and appraised changes. Deciding to seek help was often
      prompted by another person or triggered by rapid or multiple changes in a mole.
      Three of four people subsequently diagnosed with melanoma did not seek help;
      instead, their GP opportunistically noticed the lesion. CONCLUSIONS: Changing
      moles are often perceived as trivial and not signifying possible skin cancer.
      This study contributes to current national strategies to improve patient
      awareness and earlier diagnosis of cancer by highlighting factors that can
      trigger or act as barriers to seeking help.(ISRCTN79932379).

PMID- 20807442
TI  - Social structural factors that shape assisted injecting practices among injection
      drug users in Vancouver, Canada: a qualitative study.
AB  - BACKGROUND: Injection drug users (IDU) commonly seek manual assistance with
      illicit drug injections, a practice known to be associated with various health
      related harms. We investigated the social structural factors that shape risks
      related to assisted injection and the harms that may result. METHODS: Twenty semi
      structured qualitative interviews were conducted with IDU enrolled in the ACCESS
      or Vancouver Injection Drug Users Study (VIDUS) who reported requiring assistance
      injecting in the past six months. Audio-recorded interviews were transcribed
      verbatim and a thematic analysis was conducted. RESULTS: Barriers to self
      injecting included a lack of knowledge of proper injecting technique, a loss of
      accessible veins, and drug withdrawal. The exchange of money or drugs for
      assistance with injecting was common. Harms experienced by IDU requiring
      assistance injecting included theft of the drug, missed injections, overdose, and
      risk of blood-borne disease transmission. Increased vulnerability to HIV/HCV
      infection within the context of intimate relationships was represented in
      participant narratives. IDU identified a lack of services available for those who
      require assistance injecting, with notable mention of restricted use of
      Vancouver's supervised injection facility. CONCLUSIONS: This study documents
      numerous severe harms that arise from assisted injecting. Social structural
      factors that shape the risks related to assisted injection in the Vancouver
      context included intimate partner relations and social conventions requiring an
      exchange of goods for provision of injecting assistance. Health services for IDU
      who need help injecting should include targeted interventions, and supervised
      injection facilities should attempt to accommodate individuals who require
      assistance with injecting.

PMID- 20807443
TI  - Measuring quality of diabetes care by linking health care system administrative
      databases with laboratory data.
AB  - BACKGROUND: Chronic complications of diabetes can be reduced through optimal
      glycemic and lipid control as evaluated through measurement of glycosylated
      hemoglobin (A1C) and low-density lipoprotein cholesterol (LDL-C). We aimed to
      produce measures of quality of diabetes care in Saskatchewan and to identify sub
      groups at particular risk of developing complications. FINDINGS: Prevalent adult
      cases of diabetes in 2005/06 were identified from administrative databases and
      linked with A1C and LDL-C tests measured in centralized laboratories. A1C results
      were performed in 33,927 of 50,713 (66.9%) diabetes cases identified in
      Saskatchewan, and LDL-C results were performed in 12,031 of 24,207 (49.7%) cases
      identified within the province's two largest health regions. The target A1C of <=
      7.0% and the target LDL-C of <2.5 mmol/L were achieved in 48.3% and 45.1% of
      diabetes cases respectively. The proportions were lower among those who were
      female, First Nations, non-urban, younger and in lower income quintiles. The same
      groups experienced poorer glycemic control (exception females), and poorer lipid
      control (exception First Nations people). Among non-Aboriginal people, younger
      diabetic females were least likely to receive lipid lowering agents. CONCLUSIONS:
      Linkage of laboratory with administrative data is an effective method of
      assessing quality of diabetes care on a population basis and to identify sub
      groups requiring particular attention. We found that less than 50% of
      Saskatchewan people with diabetes achieved optimal glycemic and lipid control.
      Disparities were most evident among First Nations people and young women. The
      indicators described can be used to provide standardized information that would
      support quality improvement initiatives.

PMID- 20807444
TI  - Isolation of intact sub-dermal secretory cavities from Eucalyptus.
AB  - BACKGROUND: The biosynthesis of plant natural products in sub-dermal secretory
      cavities is poorly understood at the molecular level, largely due to the
      difficulty of physically isolating these structures for study. Our aim was to
      develop a protocol for isolating live and intact sub-dermal secretory cavities,
      and to do this, we used leaves from three species of Eucalyptus with cavities
      that are relatively large and rich in essential oils. RESULTS: Leaves were
      digested using a variety of commercially available enzymes. A pectinase from
      Aspergillus niger was found to allow isolation of intact cavities after a
      relatively short incubation (12 h), with no visible artifacts from digestion and
      no loss of cellular integrity or cavity contents. Several measurements indicated
      the potential of the isolated cavities for further functional studies. First, the
      cavities were found to consume oxygen at a rate that is comparable to that
      estimated from leaf respiratory rates. Second, mRNA was extracted from cavities,
      and it was used to amplify a cDNA fragment with high similarity to that of a
      monoterpene synthase. Third, the contents of the cavity lumen were extracted,
      showing an unexpectedly low abundance of volatile essential oils and a sizeable
      amount of non-volatile material, which is contrary to the widely accepted role of
      secretory cavities as predominantly essential oil repositories. CONCLUSIONS: The
      protocol described herein is likely to be adaptable to a range of Eucalyptus
      species with sub-dermal secretory cavities, and should find wide application in
      studies of the developmental and functional biology of these structures, and the
      biosynthesis of the plant natural products they contain.

PMID- 20807445
TI  - A study of the diagnostic accuracy of the PHQ-9 in primary care elderly.
AB  - BACKGROUND: The diagnostic accuracy of the Patient Health Questionnaire-9 (PHQ-9)
      for assessment of depression in elderly persons in primary care settings in the
      United States has not been previously addressed. Thus, the purpose of this study
      was to evaluate the test performance of the PHQ-9 for detecting major and minor
      depression in elderly patients in primary care. METHODS: A prospective study of
      diagnostic accuracy was conducted in two primary care, university-based clinics
      in the Pacific Northwest of the United States. Seventy-one patients aged 65 years
      or older participated; all completed the PHQ-9 and the 15-item Geriatric
      Depression Scale (GDS) and underwent the Structured Clinical Interview for
      Depression (SCID). Sensitivity, specificity, area under the receiver operating
      characteristic (ROC) curve, and likelihood ratios (LRs) were calculated for the
      PHQ-9, the PHQ-2, and the 15-item GDS for major depression alone and the
      combination of major plus minor depression. RESULTS: Two thirds of participants
      were female, with a mean age of 78 and two chronic health conditions. Twelve
      percent met SCID criteria for major depression and 13% minor depression. The PHQ
      9 had an area under the curve (AUC) of 0.87 (95% confidence interval [CI], 0.74
      1.00) for major depression, while the PHQ-2 and the 15-item GDS each had an AUC
      of 0.81 (95% CI for PHQ-2, 0.64-0.98, and for 15-item GDS, 0.70-0.91; P = 0.551).
      For major and minor depression combined, the AUC for the PHQ-9 was 0.85 (95% CI,
      0.73-0.96), for the PHQ-2, 0.80 (95% CI, 0.68-0.93), and for the 15-item GDS,
      0.71 (95% CI, 0.55-0.87; P = 0.187). CONCLUSIONS: Based on AUC values, the PHQ-9
      performs comparably to the PHQ-2 and the 15-item GDS in identifying depression
      among primary care elderly.

PMID- 20807446
TI  - Reproducibility of the airway response to an exercise protocol standardized for
      intensity, duration, and inspired air conditions, in subjects with symptoms
      suggestive of asthma.
AB  - BACKGROUND: Exercise testing to aid diagnosis of exercise-induced
      bronchoconstriction (EIB) is commonly performed. Reproducibility of the airway
      response to a standardized exercise protocol has not been reported in subjects
      being evaluated with mild symptoms suggestive of asthma but without a definite
      diagnosis. This study examined reproducibility of % fall in FEV1 and area under
      the FEV1 time curve for 30 minutes in response to two exercise tests performed
      with the same intensity and duration of exercise, and inspired air conditions.
      METHODS: Subjects with mild symptoms of asthma exercised twice within
      approximately 4 days by running for 8 minutes on a motorized treadmill breathing
      dry air at an intensity to induce a heart rate between 80-90% predicted maximum;
      reproducibility of the airway response was expressed as the 95% probability
      interval. RESULTS: Of 373 subjects challenged twice 161 were positive (>= 10%
      fall FEV1 on at least one challenge). The EIB was mild and 77% of subjects had
      <15% fall on both challenges. Agreement between results was 76.1% with 56.8%
      (212) negative (< 10% fall FEV1) and 19.3% (72) positive on both challenges. The
      remaining 23.9% of subjects had only one positive test. The 95% probability
      interval for reproducibility of the % fall in FEV1 and AUC0-30 min was +/- 9.7%
      and +/- 251% for all 278 adults and +/- 13.4% and +/- 279% for all 95 children.
      The 95% probability interval for reproducibility of % fall in FEV1 and AUC0-30
      min for the 72 subjects with two tests >= 10% fall FEV1 was +/- 14.6% and +/-
      373% and for the 34 subjects with two tests >= 15% fall FEV1 it was +/- 12.2% and
      +/- 411%. Heart rate and estimated ventilation achieved were not significantly
      different either on the two test days or when one test result was positive and
      one was negative. CONCLUSIONS: Under standardized, well controlled conditions for
      exercise challenge, the majority of subjects with mild symptoms of asthma
      demonstrated agreement in test results. Performing two tests may need to be
      considered when using exercise to exclude or diagnose EIB, when prescribing
      prophylactic treatment to prevent EIB and when designing protocols for clinical
      trials.

PMID- 20807447
TI  - Important role of indels in somatic mutations of human cancer genes.
AB  - BACKGROUND: Cancer is clonal proliferation that arises owing to mutations in a
      subset of genes that confer growth advantage. More and more cancer related genes
      are found to have accumulated somatic mutations. However, little has been
      reported about mutational patterns of insertions/deletions (indels) in these
      genes. RESULTS: We analyzed indels' abundance and distribution, the relative
      ratio between indels and somatic base substitutions and the association between
      those two forms of mutations in a large number of somatic mutations in the
      Catalogue of Somatic Mutations in Cancer database. We found a strong correlation
      between indels and base substitutions in cancer-related genes and showed that
      they tend to concentrate at the same locus in the coding sequences within the
      same samples. More importantly, a much higher proportion of indels were observed
      in somatic mutations, as compared to meiotic ones. Furthermore, our analysis
      demonstrated a great diversity of indels at some loci of cancer-related genes.
      Particularly in the genes with abundant mutations, the proportion of 3n indels in
      oncogenes is 7.9 times higher than that in tumor suppressor genes. CONCLUSIONS:
      There are three distinct patterns of indel distribution in somatic mutations:
      high proportion, great abundance and non-random distribution. Because of the
      great influence of indels on gene function (e.g., the effect of frameshift
      mutation), these patterns indicate that indels are frequently under positive
      selection and can often be the 'driver mutations' in oncogenesis. Such driver
      forces can better explain why much less frameshift mutations are in oncogenes
      while much more in tumor suppressor genes, because of their different function in
      oncogenesis. These findings contribute to our understanding of mutational
      patterns and the relationship between indels and cancer.

PMID- 20807448
TI  - Effectiveness of dry needling and injections of myofascial trigger points
      associated with plantar heel pain: a systematic review.
AB  - BACKGROUND: Plantar heel pain (plantar fasciitis) is one of the most common
      musculoskeletal pathologies of the foot. Plantar heel pain can be managed with
      dry needling and/or injection of myofascial trigger points (MTrPs) however the
      evidence for its effectiveness is uncertain. Therefore, we aimed to
      systematically review the current evidence for the effectiveness of dry needling
      and/or injections of MTrPs associated with plantar heel pain. METHODS: We
      searched specific electronic databases (MEDLINE, EMBASE, AMED, CINAHL,
      SPORTDiscus and AMI) in April 2010 to identify randomised and non-randomised
      trials. We included trials where participants diagnosed with plantar heel pain
      were treated with dry needling and/or injections (local anaesthetics, steroids,
      Botulinum toxin A and saline) alone or in combination with acupuncture. Outcome
      measures that focussed on pain and function were extracted from the data. Trials
      were assessed for quality using the Quality Index tool. RESULTS: Three quasi
      experimental trials matched the inclusion criteria: two trials found a reduction
      in pain for the use of trigger point dry needling when combined with acupuncture
      and the third found a reduction in pain using 1% lidocaine injections when
      combined with physical therapy. However, the methodological quality of the three
      trials was poor, with Quality Index scores ranging form 7 to 12 out of a possible
      score of 27. A meta-analysis was not conducted because substantial heterogeneity
      was present between trials. CONCLUSIONS: There is limited evidence for the
      effectiveness of dry needling and/or injections of MTrPs associated with plantar
      heel pain. However, the poor quality and heterogeneous nature of the included
      studies precludes definitive conclusions being made. Importantly, this review
      highlights the need for future trials to use rigorous randomised controlled
      methodology with measures such as blinding to reduce bias. We also recommend that
      such trials adhere to the Standards for Reporting Interventions in Controlled
      Trials of Acupuncture (STRICTA) to ensure transparency.

PMID- 20807449
TI  - Can bone loss be reversed by antithyroid drug therapy in premenopausal women with
      Graves' disease?
AB  - CONTEXT: Hyperthyroidism can lead to reduced bone mineral density (BMD) and
      increased fracture risk particularly in postmenopausal women, but the mechanism
      behind is still unclear. OBJECTIVE: Prospective examination of the influence of
      thyroid hormones and/or thyroid autoantibodies on BMD in premenopause. DESIGN: We
      have examined 32 premenopausal women with untreated active Graves' disease from
      time of diagnosis, during 18 months of antithyroid drug therapy (ATD) and
      additionally 18 months after discontinuing ATD. Variables of thyroid metabolism,
      calcium homeostasis and body composition were measured every 3 months. BMD of
      lumbar spine and femoral neck were measured at baseline, 18 +/- 3 and 36 +/- 3
      months. Data were compared to base line, a sex- and age matched control group and
      a group of patients with Hashimoto's thyroiditis treated with non-suppressive
      doses of levothyroxine. RESULTS: The study showed significantly (p < 0.002) lower
      BMD in the thyrotoxic state compared to the control group with subsequent
      significant improvement during 18 +/- 3 months of ATD compared to baseline (p <
      0.001). However, during the following 18 months after stopping ATD femoral neck
      BMD decreased again unrelated to age (more than 0.4% per year, p < 0,002). The
      wellestablished effect of thyrotoxicosis on calcium homeostasis was confirmed.
      The positive predictor for best BMD was TSH receptor antibodies (TRAb) while free
      T4 correlated negatively in the thyrotoxic female Graves' patients (p < 0.02 and
      p < 0.003). In healthy controls and patients with treated Graves' disease both
      TSH and T4 correlated negatively to the bone mass (BMC) (p < 0.003). CONCLUSION:
      The results indicated a clinically relevant impact of thyroid function on bone
      modulation also in premenopausal women with Graves' disease, and further
      indicated the possibility for a direct action of TRAb on bones.

PMID- 20807450
TI  - Comparing the frequency of common genetic variants and haplotypes between
      carriers and non-carriers of BRCA1 and BRCA2 deleterious mutations in Australian
      women diagnosed with breast cancer before 40 years of age.
AB  - BACKGROUND: BRCA1 and BRCA2 mutations are found in a proportion of families with
      multiple early-onset breast cancers. There are a large number of different
      deleterious mutations in both genes, none of which would be detectable using
      standard genetic association studies. Single common variants and haplotypes of
      common variants may capture groups of deleterious mutations since some low
      prevalence haplotypes of common variants occur more frequently among chromosomes
      that carry rare, deleterious mutations than chromosomes that do not. METHODS: DNA
      sequence data for BRCA1 and BRCA2 was obtained from 571 participants from the
      Australian Breast Cancer Family Study. Genetic variants were classified as either
      deleterious mutations or common genetic variants. Variants tagging common
      polymorphisms were selected and haplotypes resolved using Haploview. Their
      frequency was compared to those with and without deleterious mutations using a
      permutation test. RESULTS: A common genetic variant in BRCA1 (3232A > G) was
      found to be over-represented in deleterious mutation carriers (p = 0.05), whereas
      a common genetic variant in BRCA2 (1342A > C) occurred less frequently in
      deleterious mutation carriers (p = 0.04). All four of the common BRCA1 variants
      used to form haplotypes occurred more frequently in the deleterious mutation
      carriers when compared to the non-carriers, but there was no evidence of a
      difference in the distributions between the two groups (p = 0.34). In BRCA2, all
      four common variants were found to occur less frequently in the deleterious
      mutation carriers when compared to non-carriers, but the evidence for difference
      in the distribution between the two groups was weak (p = 0.16). Several less
      common haplotypes of common BRCA1 variants were found to be over-represented
      among deleterious mutation carriers but there was no evidence for this at the
      population level. In BRCA2, only the most common haplotype was found to occur
      more frequently in deleterious mutation carriers, with again no evidence at the
      population level. CONCLUSIONS: We observed differences in the frequency of common
      genetic variants of the BRCA1 and BRCA2 and their haplotypes between early-onset
      breast cancer cases who did and did not carry deleterious mutations in these
      genes. Although our data provide only weak evidence for a difference in
      frequencies at the population level, the number of deleterious mutation carriers
      was low and the results may yet be substantiated in a larger study using pooled
      data.

PMID- 20807451
TI  - Broader HIV-1 neutralizing antibody responses induced by envelope glycoprotein
      mutants based on the EIAV attenuated vaccine.
AB  - BACKGROUND: In order to induce a potent and cross-reactive neutralizing antibody
      (nAb), an effective envelope immunogen is crucial for many viral vaccines,
      including the vaccine for the human immunodeficiency virus (HIV). The Chinese
      equine infectious anemia virus (EIAV) attenuated vaccine has controlled the
      epidemic of this virus after its vaccination in over 70 million equine animals
      during the last 3 decades in China. Data from our past studies demonstrate that
      the Env protein of this vaccine plays a pivotal role in protecting horses from
      both homologous and heterogeneous EIAV challenges. Therefore, the amino acid
      sequence information from the Chinese EIAV attenuated vaccine, in comparison with
      the parental wild-type EIAV strains, was applied to modify the corresponding
      region of the envelope glycoprotein of HIV-1 CN54. The direction of the mutations
      was made towards the amino acids conserved in the two EIAV vaccine strains,
      distinguishing them from the two wild-type strains. The purpose of the
      modification was to enhance the immunogenicity of the HIV Env. RESULTS: The
      induced nAb by the modified HIV Env neutralized HIV-1 B and B'/C viruses at the
      highest titer of 1:270. Further studies showed that a single amino acid change in
      the C1 region accounts for the substantial enhancement in induction of anti-HIV-1
      neutralizing antibodies. CONCLUSIONS: This study shows that an HIV envelope
      modified by the information of another lentivirus vaccine induces effective
      broadly neutralizing antibodies. A single amino acid mutation was found to
      increase the immunogenicity of the HIV Env.

PMID- 20807452
TI  - How common is ecological speciation in plant-feeding insects? A 'Higher'
      Nematinae perspective.
AB  - BACKGROUND: Ecological speciation is a process in which a transiently resource
      polymorphic species divides into two specialized sister lineages as a result of
      divergent selection pressures caused by the use of multiple niches or
      environments. Ecology-based speciation has been studied intensively in plant
      feeding insects, in which both sympatric and allopatric shifts onto novel host
      plants could speed up diversification. However, while numerous examples of
      species pairs likely to have originated by resource shifts have been found, the
      overall importance of ecological speciation in relation to other, non-ecological
      speciation modes remains unknown. Here, we apply phylogenetic information on
      sawflies belonging to the 'Higher' Nematinae (Hymenoptera: Tenthredinidae) to
      infer the frequency of niche shifts in relation to speciation events. RESULTS:
      Phylogenetic trees reconstructed on the basis of DNA sequence data show that the
      diversification of higher nematines has involved frequent shifts in larval
      feeding habits and in the use of plant taxa. However, the inferred number of
      resource shifts is considerably lower than the number of past speciation events,
      indicating that the majority of divergences have occurred by non-ecological
      allopatric speciation; based on a time-corrected analysis of sister species, we
      estimate that a maximum of c. 20% of lineage splits have been triggered by a
      change in resource use. In addition, we find that postspeciational changes in
      geographic distributions have led to broad sympatry in many species having
      identical host-plant ranges. CONCLUSION: Our analysis indicates that the
      importance of niche shifts for the diversification of herbivorous insects is at
      present implicitly and explicitly overestimated. In the case of the Higher
      Nematinae, employing a time correction for sister-species comparisons lowered the
      proportion of apparent ecology-based speciation events from c. 50-60% to around
      20%, but such corrections are still lacking in other herbivore groups. The
      observed convergent but asynchronous shifting among dominant northern plant taxa
      in many higher-nematine clades, in combination with the broad overlaps in the
      geographic distributions of numerous nematine species occupying near-identical
      niches, indicates that host-plant shifts and herbivore community assembly are
      largely unconstrained by direct or indirect competition among species. More
      phylogeny-based studies on connections between niche diversification and
      speciation are needed across many insect taxa, especially in groups that exhibit
      few host shifts in relation to speciation.

PMID- 20807453
TI  - Evidence-based medicine training during residency: a randomized controlled trial
      of efficacy.
AB  - BACKGROUND: Evidence-based medicine (EBM) has been widely integrated into
      residency curricula, although results of randomized controlled trials and long
      term outcomes of EBM educational interventions are lacking. We sought to
      determine if an EBM workshop improved internal medicine residents' EBM knowledge
      and skills and use of secondary evidence resources. METHODS: This randomized
      controlled trial included 48 internal medicine residents at an academic medical
      center. Twenty-three residents were randomized to attend a 4-hour interactive
      workshop in their PGY-2 year. All residents completed a 25-item EBM knowledge and
      skills test and a self-reported survey of literature searching and resource usage
      in their PGY-1, PGY-2, and PGY-3 years. RESULTS: There was no difference in mean
      EBM test scores between the workshop and control groups at PGY-2 or PGY-3.
      However, mean EBM test scores significantly increased over time for both groups
      in PGY-2 and PGY-3. Literature searches, and resource usage also increased
      significantly in both groups after the PGY-1 year. CONCLUSIONS: We were unable to
      detect a difference in EBM knowledge between residents who did and did not
      participate in our workshop. Significant improvement over time in EBM scores,
      however, suggests EBM skills were learned during residency. Future rigorous
      studies should determine the best methods for improving residents' EBM skills as
      well as their ability to apply evidence during clinical practice.

PMID- 20807456
TI  - Early verb learning in 20-month-old Japanese-speaking children.
AB  - The present study investigated whether children's representations of
      morphosyntactic information are abstract enough to guide early verb learning.
      Using an infant-controlled habituation paradigm with a switch design, Japanese
      speaking children aged 1 ; 8 were habituated to two different events in which an
      object was engaging in an action. Each event was paired with a novel word
      embedded in a single intransitive verb sentence frame. The results indicated that
      only 40% of the children were able to map a novel verb onto the action when the
      mapping task was complex. However, by simplifying the mapping task, 88% of the
      children succeeded in verb-action mapping. There were no differences in
      perceptual salience between the agent and action switches in the task. These
      results provide strong evidence that Japanese-speaking children aged 1 ; 8 are
      able to use an intransitive verb sentence frame to guide early verb learning
      unless the mapping task consumes too much of their cognitive resources.

PMID- 20807454
TI  - Role of structural MRI in Alzheimer's disease.
AB  - Atrophy measured on structural magnetic resonance imaging (sMRI) is a powerful
      biomarker of the stage and intensity of the neurodegenerative aspect of
      Alzheimer's disease (AD) pathology. In this review, we will discuss the role of
      sMRI as an AD biomarker by summarizing (a) the most commonly used methods to
      extract information from sMRI images, (b) the different roles in which sMRI can
      be used as an AD biomarker, and (c) comparisons of sMRI with other major AD
      biomarkers.

PMID- 20807457
TI  - Dietary RRR-alpha-tocopherol succinate attenuates lipopolysaccharide-induced
      inflammatory cytokines secretion in broiler chicks.
AB  - The anti-inflammatory effects of two esters of a-tocopherol (alpha-TOH), all-rac
      alpha-TOH acetate (DL-alpha-TOA) and RRR-alpha-TOH succinate (D-alpha-TOS), on
      broilers repeatedly challenged with lipopolysaccharide (LPS) were investigated.
      Three hundred and twenty 1-d-old broiler chicks were allotted into four treatment
      groups and fed on a control diet (30 mg/kg DL-alpha-TOA) or diets containing 10,
      30, 50 mg/kg D-alpha-TOS. Half of the birds from each treatment group were
      challenged with 0.9% NaCl solution or LPS (250 MUg/kg body weight) at 16, 18 and
      20 d of age. The results indicated that the pretreatment of birds with 50 mg/kg D
      alpha-TOS markedly reduced serum PGE2 secretion and increased the concentrations
      of serum or hepatic alpha-TOH. When LPS-challenged birds were pretreated with 30
      or 50 mg/kg D-alpha-TOS, the increases of plasma and splenic concentrations of
      interferon-gamma, IL-1beta, IL-2, IL-6, IL-4 and IL-10 were dramatically
      attenuated. Also, a significant decrease of hepatic reactive oxygen species (ROS)
      and hepatic or splenic phosphokinase C (PKC) activities was found in birds
      pretreated with 30 or 50 mg/kg D-alpha-TOS. Furthermore, D-alpha-TOS inhibited
      the activation of NF-kappaB by preventing the degradation of inhibitory
      kappaBalpha. In conclusion, D-alpha-TOS is able to prevent LPS-induced
      inflammation response in vivo. The beneficial effect may depend on suppressing
      the secretion of various plasma and splenic inflammatory mediators through
      inhibiting NF-kappaB activation and by blocking ROS signalling, in which PKC may
      play an assistant role.

PMID- 20807455
TI  - Molecular insights into amyloid regulation by membrane cholesterol and
      sphingolipids: common mechanisms in neurodegenerative diseases.
AB  - Alzheimer, Parkinson and other neurodegenerative diseases involve a series of
      brain proteins, referred to as 'amyloidogenic proteins', with exceptional
      conformational plasticity and a high propensity for self-aggregation. Although
      the mechanisms by which amyloidogenic proteins kill neural cells are not fully
      understood, a common feature is the concentration of unstructured amyloidogenic
      monomers on bidimensional membrane lattices. Membrane-bound monomers undergo a
      series of lipid-dependent conformational changes, leading to the formation of
      oligomers of varying toxicity rich in beta-sheet structures (annular pores,
      amyloid fibrils) or in alpha-helix structures (transmembrane channels). Condensed
      membrane nano- or microdomains formed by sphingolipids and cholesterol are
      privileged sites for the binding and oligomerisation of amyloidogenic proteins.
      By controlling the balance between unstructured monomers and alpha or beta
      conformers (the chaperone effect), sphingolipids can either inhibit or stimulate
      the oligomerisation of amyloidogenic proteins. Cholesterol has a dual role:
      regulation of protein-sphingolipid interactions through a fine tuning of
      sphingolipid conformation (indirect effect), and facilitation of pore (or
      channel) formation through direct binding to amyloidogenic proteins. Deciphering
      this complex network of molecular interactions in the context of age- and disease
      related evolution of brain lipid expression will help understanding of how
      amyloidogenic proteins induce neural toxicity and will stimulate the development
      of innovative therapies for neurodegenerative diseases.

PMID- 20807458
TI  - Redox-modulatory vitamins and minerals that prospectively predict mortality in
      older British people: the National Diet and Nutrition Survey of people aged 65
      years and over.
AB  - The predictive power, for total, vascular, cancer and respiratory mortality, of
      selected redox-modulatory (vitamin and mineral nutrient) indices measured at
      baseline, was studied in the British National Diet and Nutrition Survey
      (community-living subset) of people aged 65 years and over. Mortality status and
      its primary and underlying causes were recorded for 1054 (mean age 76.6 (sd 7.4)
      years and 49.0 % female) participants, from the baseline survey in 1994-5 until
      September 2008. During this interval, 74 % of the male and 62 % of the female
      participants died. Total mortality was significantly predicted by baseline plasma
      concentrations (per sd) of vitamin C (hazard ratio (HR) 0.81; 95 % CI 0.74,
      0.88), alpha-carotene (HR 0.90; 95 % CI 0.81, 0.99), Se (HR 0.76; 95 % CI 0.69,
      0.84), Zn (HR 0.79; 95 % CI 0.72, 0.87), Cu (HR 1.27; 95 % CI 1.14, 1.42) and Fe
      (HR 0.81; 95 % CI 0.74, 0.89). Total mortality was also significantly predicted
      by baseline dietary intakes (per sd) of food energy (HR 0.86; 95 % CI 0.79,
      0.94), vitamin C (HR 0.88; 95 % CI 0.80, 0.94), carotenoids (HR 0.89; 95 % CI
      0.83, 0.96), Zn (HR 0.89; 95 % CI 0.82, 0.96) and Cu (HR 0.91; 95 % CI 0.84,
      1.00). Prediction patterns and significance for primary vascular, cancer and
      respiratory mortality differed in certain respects, but not fundamentally. Model
      adjustment for known disease or mortality risk predictors resulted in loss of
      significance for some of the indices; however, plasma Se and Zn, and food energy
      remained significant predictors. We conclude that total and primary vascular,
      cancer and respiratory mortality in older British people of both sexes is
      predicted by several biochemical indices of redox-modulatory nutrients, some of
      which may reflect the respondents' acute-phase status at baseline, whereas others
      may reflect the healthiness of their lifestyle.

PMID- 20807460
TI  - Red meat from animals offered a grass diet increases plasma and platelet n-3 PUFA
      in healthy consumers.
AB  - Red meat from grass-fed animals, compared with concentrate-fed animals, contains
      increased concentrations of long-chain (LC) n-3 PUFA. However, the effects of red
      meat consumption from grass-fed animals on consumer blood concentrations of LC n
      3 PUFA are unknown. The aim of the present study was to compare the effects on
      plasma and platelet LC n-3 PUFA status of consuming red meat produced from either
      grass-fed animals or concentrate-fed animals. A randomised, double-blinded,
      dietary intervention study was carried out for 4 weeks on healthy subjects who
      replaced their habitual red meat intake with three portions per week of red meat
      (beef and lamb) from animals offered a finishing diet of either grass or
      concentrate (n 20 consumers). Plasma and platelet fatty acid composition, dietary
      intake, blood pressure, and serum lipids and lipoproteins were analysed at
      baseline and post-intervention. Dietary intakes of total n-3 PUFA, as well as
      plasma and platelet concentrations of LC n-3 PUFA, were significantly higher in
      those subjects who consumed red meat from grass-fed animals compared with those
      who consumed red meat from concentrate-fed animals (P < 0.05). No significant
      differences in concentrations of serum cholesterol, TAG or blood pressure were
      observed between groups. Consuming red meat from grass-fed animals compared with
      concentrate-fed animals as part of the habitual diet can significantly increase
      consumer plasma and platelet LC n-3 PUFA status. As a result, red meat from grass
      fed animals may contribute to dietary intakes of LC n-3 PUFA in populations where
      red meat is habitually consumed.

PMID- 20807459
TI  - Whole and fractionated yellow pea flours reduce fasting insulin and insulin
      resistance in hypercholesterolaemic and overweight human subjects.
AB  - The objective of the present study was to compare whole pea flour (WPF) to
      fractionated pea flour (FPF; hulls only) for their ability to reduce risk factors
      associated with CVD and diabetes in overweight hypercholesterolaemic individuals.
      Using a cross-over design, twenty-three hypercholesterolaemic overweight men and
      women received two-treatment muffins/d containing WPF, FPF or white wheat flour
      (WF) for 28 d, followed by 28 d washout periods. Daily doses of WPF and FPF
      complied with the United States Department of Agriculture's recommended level of
      intake of half a cup of pulses/d (approximately 50 g/d). Dietary energy
      requirements were calculated for each study subject, and volunteers were only
      permitted to eat food supplied by the study personnel. Fasting insulin, body
      composition, urinary enterolactone levels, postprandial glucose response, as well
      as fasting lipid and glucose concentrations, were assessed at the beginning and
      at the end of each treatment. Insulin concentrations for WPF (37.8 (SEM 3.4)
      pmol/ml, P = 0.021) and FPF (40.5 (SEM 3.4) pmol/ml, P = 0.037) were lower
      compared with WF (50.7 (SEM 3.4) pmol/ml). Insulin homeostasis modelling
      assessment showed that consumption of WPF and FPF decreased (P < 0.05) estimates
      of insulin resistance (IR) compared with WF. Android:gynoid fat ratios in women
      participants were lower (P = 0.027) in the WPF (1.01 (sem 0.01) group compared
      with the WF group (1.06 (SEM 0.01). Urinary enterolactone levels tended to be
      higher (P = 0.087) in WPF compared with WF. Neither treatment altered circulating
      fasting lipids or glucose concentrations. In conclusion, under a controlled diet
      paradigm, a daily consumption of whole and fractionated yellow pea flours at
      doses equivalent to half a cup of yellow peas/d reduced IR, while WPF reduced
      android adiposity in women.

PMID- 20807461
TI  - Relationship between proteome changes of Longissimus muscle and intramuscular fat
      content in finishing pigs fed conjugated linoleic acid.
AB  - The present experiment was conducted to determine proteome changes in Longissimus
      muscle of finishing pigs fed conjugated linoleic acid (CLA), in association with
      alteration of intramuscular fat content. Previously, seventy-two Duroc * Landrace
      * Large White gilts (approximately 60 kg) had been fed maize-soyabean meal-based
      diets with 0, 12.5 and 25 g CLA/kg diet. The CLA contained 369.1 mg/g cis-9,
      trans-11 CLA, 374.6 mg/g trans-10, cis-12 CLA and 53.7 mg/g other isomers. Six
      pigs per treatment were slaughtered when they reached a body weight of
      approximately 100 kg. Data published from a previous experiment demonstrated that
      supplementation with 12.5 or 25 g CLA/kg diet increased intramuscular fat content
      (P < 0.05). The present study investigated the proteome changes in Longissimus
      muscle of control and pigs supplemented with 25 g CLA/kg diet. CLA significantly
      influenced the abundance of proteins related to energy metabolism, fatty acid
      oxidation and synthesis, amino acid metabolism, defence, transport and other
      miscellaneous processes (P < 0.05). The increase in intramuscular fat content was
      positively correlated with the increased abundance of carbonic anhydrase 3 and
      aspartate aminotransferase (P < 0.05). We suggest that the proteome changes in
      Longissimus muscle contributed to greater intramuscular lipid content in CLA
      supplemented pigs.

PMID- 20807462
TI  - Genoprotective effects of green tea (Camellia sinensis) in human  subjects: 
      results of a controlled supplementation trial.
AB  - Green tea is rich in polyphenolic antioxidants and has widely reported but
      largely unsubstantiated health benefits. In the present study, genoprotective
      effects of two types of green tea were studied both in an in vitro and in a human
      supplementation trial. For the in vitro study, human lymphocytes were pre
      incubated in tea (0.005-0.1 %, w/v), washed and subjected to oxidant challenge
      induced by H2O2. In a placebo-controlled, cross-over supplementation study,
      eighteen healthy volunteers took 2 x 150 ml/d of 1% (w/v) green tea ('Longjing'
      green tea or 'screw-shaped' green tea) or water (control) for 4 weeks (n 6).
      Subjects took all the three treatments in a random order, with 6 weeks' washout
      between each treatment. Fasting blood and urine were collected before and after
      each treatment. The comet assay was used to measure the resistance of lymphocytic
      DNA to H2O2-induced challenge. Basal oxidation-induced DNA damage was measured
      using the formamidopyrimidine glycosylase (Fpg) enzyme-assisted comet assay.
      Urine 7,8-dihydro-2-deoxyguanosine (8-oxodG, mol/mmol creatinine), a biomarker of
      whole-body oxidative stress, was measured by liquid chromatography with tandem
      MS. In vitro testing results of tea-treated cells showed increased (P < 0.05)
      resistance of DNA to the challenge. In the supplementation trial, a significant
      (P < 0.05) increase in resistance was also observed. Furthermore, the FPg comet
      data showed .20% decrease in DNA damage with tea supplementation: mean and
      standard deviation changes in %DNA in comet tail in the Fpg-assisted comet assay
      were: -5.96 (SD 3.83) % after Longjing tea; -6.22 (SD 3.34) % after screw-shaped
      tea; +0.91 (SD 5.79) % after water (P < 0.05). No significant changes in urine 8
      oxodG were seen. The results indicate that green tea has significant
      genoprotective effects and provide evidence for green tea as a 'functional food'.

PMID- 20807463
TI  - Controlling energetic intake based on a novel logistic regression  model for  the
      metabolic syndrome in a Chinese population.
AB  - The present study was designed to develop a novel method of energy calculation
      for controlling energetic intake in patients with the metabolic syndrome.
      Demographics and dietary data were recorded for 2582 obese subjects. Nutritional
      education was applied to all the patients. One year later, the data on age, sex,
      activity intensity coefficient, waistline, environmental temperature and BMI in
      subjects who lost >= 5% body weight were entered into a multivariate logistic
      regression analysis model. Energy requirement was calculated from the results of
      multivariate logistic regression. Four hundred and thirty-four metabolic syndrome
      patients were then randomly divided into the treated group (216) and the control
      group (218). The energetic intake in the experimental group was controlled based
      on the new energy requirement model. The traditional energy exchange method was
      used in the control group. The independent factors predicting metabolic syndrome
      prognosis, such as age, sex, activity intensity coefficient, waistline,
      environmental temperature and BMI, were identified by multivariate logistic
      regression analysis. The energy requirement model was then constructed by
      logistic regression analysis. After 6 months of energetic intake control based on
      the new model, the parameters of the experimental group were significantly
      different from those of the controls (all P < 0.05): waistline, 89.65 (SD 5.54)
      v. 91.97 (SD 4.78) cm; BMI, 24.67 (SD 3.54) v. 25.87 (SD 2.65) kg/m2; fasting
      blood glucose, 6.9 (SD 3.6) v. 8.7 (SD 4.6) mmol/l; 2 h PG, 8.7 (SD 5.7) v. 10.7
      (SD 4.5) mmol/l; HbA1c, 7.7 (SD 1.6) v. 8.9 (SD 2.6) %; homoeostasis model
      insulin resistance index, 3.14 (SD 1.62) v. 4.32 (SD 2.25). The new energy
      requirement model can effectively improve the clinical outcomes of controlling
      energetic intake in metabolic syndrome patients.

PMID- 20807465
TI  - Influences on the quality of young children's diets: the importance of maternal
      food choices.
AB  - It is recognised that eating habits established in early childhood may track into
      adult life. Developing effective interventions to promote healthier patterns of
      eating throughout the life course requires a greater understanding of the diets
      of young children and the factors that influence early dietary patterns. In a
      longitudinal UK cohort study, we assessed the diets of 1640 children at age 3
      years using an interviewer-administered FFQ and examined the influence of
      maternal and family factors on the quality of the children's diets. To describe
      dietary quality, we used a principal components analysis-defined pattern of foods
      that is consistent with healthy eating recommendations. This was termed a
      'prudent' diet pattern and was characterised by high intakes of fruit, vegetables
      and wholemeal bread, but by low intakes of white bread, confectionery, chips and
      roast potatoes. The key influence on the quality of the children's diets was the
      quality of their mother's diets; alone it accounted for almost a third of the
      variance in child's dietary quality. Mothers who had better-quality diets, which
      complied with dietary recommendations, were more likely to have children with
      comparable diets. This relationship remained strong even after adjustment for all
      other factors considered, including maternal educational attainment, BMI and
      smoking, and the child's birth order and the time spent watching television. Our
      data provide strong evidence of shared family patterns of diet and suggest that
      interventions to improve the quality of young women's diets could be effective in
      improving the quality of their children's diets.

PMID- 20807464
TI  - Breakfast consumption and physical activity in British adolescents.
AB  - Studies show an inverse relationship between breakfast frequency and weight gain.
      This may reflect poor eating habits generally and associated low physical
      activity (PA) or direct impacts of breakfast on mechanisms leading to lethargy
      and reduced PA. The relationship between breakfast frequency and PA is
      inconclusive. We aimed to determine whether breakfast frequency is associated
      with PA levels in British adolescents independent of body composition and socio
      economic status (SES). Habitual breakfast frequency (self-report questionnaire)
      was assessed in 877 adolescents (43% male, age 14.5 (SD 0.5) years old). PA was
      measured over 5 d (accelerometry, average counts/ min; cpm). Associations between
      daily PA and breakfast frequency were assessed using linear regression adjusted
      for body fat percentage and SES. Effect modification by sex and associations with
      PA during the morning (06.00-12.00 hours) were explored. For boys, there were no
      significant associations between breakfast frequency and PA. For girls, less
      frequent breakfast consumption was significantly associated with lower PA (cpm)
      during the morning (occasional v. frequent b - 6.1 (95% CI - 11.1, -1.1), P =
      0.017) when adjusted for body fat percentage and SES. There were no associations
      between PA and breakfast consumption over the whole day; however, for girls, less
      frequent breakfast consumption may be associated with lower PA levels during the
      morning, suggesting that breakfast consumption should perhaps be taken into
      consideration when aiming to promote PA in adolescent girls.

PMID- 20807466
TI  - beta-Cryptoxanthin- and alpha-carotene-rich foods have greater apparent
      bioavailability than beta-carotene-rich foods in Western diets.
AB  - beta-Carotene (BC), beta-cryptoxanthin (CX) and alpha-carotene (AC) are common
      carotenoids that form retinol. The amount of retinol (vitamin A) formed from
      carotenoid-rich foods should depend chiefly on the bioavailability (absorption
      and circulation time in the body) of carotenoids from their major food sources
      and the selectivity and reactivity of carotene cleavage enzymes towards them. The
      objective of the present study was to estimate the apparent bioavailability of
      the major sources of provitamin A (AC, BC and CX) from the diet by comparing the
      concentrations of these carotenoids in blood to their dietary intakes. Dietary
      intakes were estimated by FFQ (three studies in this laboratory, n 86; apparent
      bioavailability calculated for six other studies, n 5738) or by food record (two
      studies in our laboratory, n 59; apparent bioavailability calculated for two
      other studies, n 54). Carotenoid concentrations were measured by reversed-phase
      HPLC. Apparent bioavailability was calculated as the ratio of concentration in
      the blood to carotenoid intake. Then apparent bioavailabilities for AC and CX
      were compared to BC. Eating comparable amounts of AC-, CX- and BC-rich foods
      resulted in 53 % greater AC (99 % CI 23, 83) and 725 % greater CX (99 % CI 535,
      915) concentrations in the blood. This suggests that the apparent bioavailability
      of CX from typical diets is greater than that of BC. Thus, CX-rich foods might be
      better sources of vitamin A than expected.

PMID- 20807467
TI  - Influence of dietary modifications on the blood pressure response to 
      antihypertensive medication.
AB  - Identifying dietary modifications that potentiate the blood pressure (BP)
      lowering effects of antihypertensive medications and that are practical for free
      living people may assist in achieving BP reduction goals. We assessed whether two
      dietary patterns were effective in lowering BP in persons on antihypertensive
      therapy and in those not on therapy. Ninety-four participants (38/56
      females/males), aged 55.6 (SD 9.9) years, consumed two 4-week dietary regimens in
      random order (Dietary Approaches to Stop Hypertension (DASH)-type diet and low-
      Na high-K (LNAHK) diet) with a control diet before each phase. Seated home BP was
      measured daily for the last 2 weeks in each phase. Participants were grouped
      based on antihypertensive drug therapy. The LNAHK diet produced a greater fall in
      systolic BP (SBP) in those on antihypertensive therapy (-6.2 (SD 6.0) mmHg) than
      in those not on antihypertensive therapy (-2.8 (SD 4.0) mmHg) (P = 0.036), and
      this was greatest for those on renin-angiotensin system (RAS) blocker therapy (
      9.5 (SD 6.4) mmHg) (interaction P = 0.007). The fall in SBP on the DASH-type
      diet, in those on therapy (overall -1.1 (SD 6.2) mmHg; renin-angiotensin blocker
      therapy -4.2 (SD 4.7) mmHg), was not as marked as that observed on the LNAHK
      diet. Dietary modifications are an important part of all hypertension management
      regimens, and a low-Na and high-K diet enhances the BP-lowering effect of
      antihypertensive medications, particularly those targeting the RAS.

PMID- 20807468
TI  - Studies on absorption and metabolism of palatinose (isomaltulose) in rats.
AB  - We evaluated the absorption and metabolism of palatinose in rats by the
      carbohydrate load test and the 13C- and H2-breath tests. We compared the results
      of these tests with those of sucrose, since sucrose is an isomer of palatinose
      and generally known to be degraded and absorbed from the small intestine. In the
      carbohydrate load test, blood glucose and plasma insulin levels after oral
      administration of palatinose rose more gradually and reached a maximum that was
      lower than that after sucrose administration. In the 13C-breath test, rats were
      orally administrated [1-13C]sucrose or [1-13C]palatinose and housed in a chamber.
      The expired air in the chamber was collected, and the level of 13CO2 in the
      expired air was measured at appropriate intervals for 360 min. The value of time
      taken to reach the maximum concentration for expired 13CO2 from [1-13Cglucose]
      ([1-13Cglc]) and [1-13Cfructose] ([1-13Cfru]) palatinose was significantly longer
      than that from [1-13Cglc] and [1-13Cfru]sucrose, respectively. The value of area
      under the curve (AUC) for [1-13Cglc]palatinose was larger than that for [1
      13Cglc]sucrose, but AUC for [1-13Cfru] showed no difference between palatinose
      and sucrose. In the H2-breath test, the concentration of H2 in the expired air
      was measured for 420 min. H2 was hardly detected with both palatinose and sucrose
      and no significant difference was observed between the two groups. These results
      suggest that palatinose is utilised in vivo at a rate equal to that of sucrose.

PMID- 20807470
TI  - Gamma Knife radiosurgery in pituitary adenomas: Why, who, and how to treat?
AB  - Pituitary adenomas are benign tumors that can be either secreting (acromegaly,
      Cushing's disease, prolactinomas) or non-secreting. Transsphenoidal neurosurgery
      is the gold standard treatment; however, it is not always effective. Gamma Knife
      radiosurgery is a specific modality of stereotactic radiosurgery, a precise
      radiation technique. Several studies reported the efficacy and low risk of
      adverse effects induced by this technique: in secreting pituitary adenomas,
      hypersecretion is controlled in about 50% of cases and tumor volume is stabilized
      or decreased in 80-90% of cases, making Gamma Knife a valuable adjunctive or
      first-line treatment. As hormone levels decrease progressively, the main drawback
      is the longer time to remission (12-60 months), requiring an additional treatment
      during this period. Hypopituitarism is the main side effect, observed in 20-40%
      cases. Gamma Knife is thus useful in the therapeutic algorithms of pituitary
      adenomas in well-defined indications, mainly low secreting small lesions well
      identified on magnetic resonance imaging (MRI).

PMID- 20807469
TI  - A multicentred randomised controlled trial of a primary care-based cognitive
      behavioural programme for low back pain. The Back Skills Training (BeST) trial.
AB  - OBJECTIVES: To estimate the clinical effectiveness of active management (AM) in
      general practice versus AM plus a group-based, professionally led cognitive
      behavioural approach (CBA) for subacute and chronic low back pain (LBP) and to
      measure the cost of each strategy over a period of 12 months and estimate cost
      effectiveness. DESIGN: Pragmatic multicentred randomised controlled trial with
      investigator-blinded assessment of outcomes. SETTING: Fifty-six general practices
      from seven English regions. PARTICIPANTS: People with subacute and chronic LBP
      who were experiencing symptoms that were at least moderately troublesome.
      INTERVENTIONS: Participants were randomised (in a ratio of 2:1) to receive either
      AM+CBA or AM alone. MAIN OUTCOME MEASURES: Primary outcomes were the Roland
      Morris Disability Questionnaire (RMQ) and the Modified Von Korff Scale (MVK),
      which measure LBP and disability. Secondary outcomes included mental and physical
      health-related quality of life (Short Form 12-item health survey), health status,
      fear avoidance beliefs and pain self-efficacy. Cost-utility of CBA was considered
      from both the UK NHS perspective and a broader health-care perspective, including
      both NHS costs and costs of privately purchased goods and services related to
      LBP. Quality-adjusted life-years (QALYs) were calculated from the five-item
      EuroQoL. RESULTS: Between April 2005 and April 2007, 701 participants were
      randomised: 233 to AM and 468 to AM+CBA. Of these, 420 were female. The mean age
      of participants was 54 years and mean baseline RMQ was 8.7. Outcome data were
      obtained for 85% of participants at 12 months. Benefits were seen across a range
      of outcome measures in favour of CBA with no evidence of group or therapist
      effects. CBA resulted in at least twice as much improvement as AM. Mean
      additional improvement in the CBA arm was 1.1 [95% confidence interval (CI) 0.4
      to 1.7], 1.4 (95% CI 0.7 to 2.1) and 1.3 (95% CI 0.6 to 2.1) change points in the
      RMQ at 3, 6 and 12 months respectively. Additional improvement in MVK pain was
      6.8 (95% CI 3.5 to 10.2), 8.0 (95% CI 4.3 to 11.7) and 7.0 (95% CI 3.2 to 10.7)
      points, and in MVK disability was 4.3 (95% CI 0.4 to 8.2), 8.1 (95% CI 4.1 to
      12.0) and 8.4 (95% CI 4.4 to 12.4) points at 3, 6 and 12 months respectively. At
      12 months, 60% of the AM+CBA arm and 31% of the AM arm reported some or complete
      recovery. Mean cost of attending a CBA course was 187 pounds per participant with
      an additional benefit in QALYs of 0.099 and an additional cost of 178.06 pounds.
      Incremental cost-effectiveness ratio was 1786.00 pounds. Probability of CBA being
      cost-effective reached 90% at about 3000 pounds and remained at that level or
      above; at a cost-effectiveness threshold of 20,000 pounds the CBA group had an
      almost 100% probability of being considered cost-effective. User perspectives on
      the acceptability of group treatments were sought through semi-structured
      interviews. Most were familiar with key messages of AM; most who had attended any
      group sessions had retained key messages from the sessions and two-thirds talked
      about a reduction in fear avoidance and changes in their behaviour. Group
      sessions appeared to provide reassurance, lessen isolation and enable
      participants to learn strategies from each other. CONCLUSIONS: Long-term
      effectiveness and cost-effectiveness of CBA in treating subacute and chronic LBP
      was shown, making this intervention attractive to patients, clinicians and
      purchasers. Short-term (3-month) clinical effects were similar to those found in
      high-quality studies of other therapies and benefits were maintained and
      increased over the long term (12 months). Cost per QALY was about half that of
      competing interventions for LBP and because the intervention can be delivered by
      existing NHS staff following brief training, the back skills training programme
      could be implemented within the NHS with relative ease. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN37807450. FUNDING: The National Institute for
      Health Research Health Technology Assessment programme.

PMID- 20807471
TI  - The evolution of antibiotic resistance: insight into the roles of molecular
      mechanisms of resistance and treatment context.
AB  - The widespread use of antibiotics has markedly improved public health over the
      last 60 years. However, the efficacy of antibiotic treatment is rapidly
      decreasing as a result of the continual spread of antibiotic resistance in
      pathogen populations. The evolution of antibiotic resistance is an amazingly
      simple example of adaptation by natural selection, and there is growing interest
      among evolutionary biologists in using evolutionary principles to help understand
      and combat the spread of resistance in pathogen populations. In this article, we
      review recent progress in our understanding of the underlying evolutionary forces
      that drive antibiotic resistance. Recent work has shown that both the mechanisms
      of antibiotic action and resistance, as well as the treatment context in which
      resistance evolves, influence the evolution of resistance in predictable ways. We
      argue that developing predictive models of resistance evolution that can be used
      to prevent the spread of resistance in pathogen populations requires integrating
      the treatment context and the molecular biology of resistance into the same
      evolutionary framework.

PMID- 20807472
TI  - Probiotics -- a viable therapeutic alternative for enteric infections especially
      in the developing world.
AB  - This review focuses on the most recent advances in the application of probiotics
      as potential therapeutics for the developing world, from the treatment of chronic
      and acute enteric infections and their associated diarrheal complexes to the
      development of designer probiotics for controlling HIV and as novel mucosal
      vaccine delivery vehicles.

PMID- 20807473
TI  - Antibodies in transplantation.
AB  - Transplantation of cells, tissues, and organs from one individual to another can
      incite the production of antibodies specific for foreign antigens, especially
      major histocompatibility antigens, in the graft. Antibodies specific for a graft
      provide an index of immunity and a potential trigger for injury and rejection.
      However, the index of immunity can sometimes miss antibody-mediated rejection and
      besides causing injury the antibodies against a graft can also protect a graft
      from injury by blocking immune recognition, called enhancement, regulating
      activation of complement, and inducing changes in the graft that resist damage.
      Reviewed here are potential limitations in the use of antibodies as an index of
      immunity and the ways antibodies cause and/or prevent injury.

PMID- 20807475
TI  - Does large scale DNA sequencing of patient and tumor DNA yet provide clinically
      actionable information?
AB  - There have been several publications recently that reported DNA sequence
      alterations in human tumors. There are gene deletions, amplifications, point
      mutations, translocations, and other genome changes in these samples compared to
      normal controls. There is also considerable variation in the number of such
      changes seen in different cancers. Some of the changes particularly those that
      are mutations in genes driving cellular proliferation will be useful clinically
      and could be used to monitor disease. At the present time, however, there are
      more cost effective ways than whole genome sequencing to derive "clinically
      actionable information" from the molecular analysis of patients and their tumors
      when they come into the clinic. The number of clinical options available for
      patients stratified by molecular diagnostics may actually be limited more by the
      specific treatments available rather than by the ability to stratify the patients
      in the first place.

PMID- 20807474
TI  - The genetics of systemic sclerosis.
AB  - Systemic sclerosis (SSc, scleroderma) is an autoimmune disease clinically
      characterized by progressive fibrosis in the skin and internal organs. While the
      pathogenesis of SSc is not completely understood, familial studies and genetic
      studies suggest that SSc is a complex polygenic disease. In the current review,
      we will discuss recent studies investigating genetic susceptibility to SSc.
      Candidate gene studies have identified critical immunoregulatory genes and gene
      regions including BANK1, FAM167A-BLK, IL23R, IRF5, STAT4, TBX21, and TNFSF4 as
      susceptibility genes for the development of SSc. More recently a genome-wide
      association study has been performed and identified CD247 (CD3-zeta) as a novel
      genetic risk factor for the susceptibility to SSc. Together these genetic
      association studies have substantially advanced our understanding of SSc
      pathogenesis and form the foundation for future studies seeking to understand the
      complexities of SSc.

PMID- 20807476
TI  - Enteroviral pathogenesis of type 1 diabetes.
AB  - Type 1 diabetes (T1D) is an autoimmune disease characterized by the disturbance
      of pancreatic insulin-producing cells, which results in hyperglycemia. The
      disease is associated with severe complications that impair the quality of life
      of individuals. The cause of T1D is unknown. Development of the disease is the
      result of interactions between immunological, genetic, and environmental factors.
      Viruses are thought to play an important role in the initiation or acceleration
      of the disease. This is an important issue since it opens the possibility to
      develop new preventive and therapeutic strategies to fight the disease. The role
      of enteroviruses in the development of T1D, in particular type B
      coxsackieviruses, is supported by epidemiological observations. It has been
      demonstrated that enterovirus infections were significantly more common in
      recently diagnosed diabetic patients, compared with control subjects. Enteroviral
      RNA and/or proteins can be detected in blood samples and intestine biopsies of
      patients with T1D. The hypothesis of a relationship between enteroviruses and the
      disease has been strengthened by the presence of enteroviral components or
      infectious particles in the pancreas of patients with T1D. In this review,
      arguments in favor of a relationship between enterovirus infections and T1D and
      the mechanisms of the enteroviral pathogenesis of the disease are presented.

PMID- 20807477
TI  - A role for lysophosphatidic acid and sphingosine 1-phosphate in the pathogenesis
      of systemic sclerosis.
AB  - Systemic sclerosis (SSc) is a complex fibrosing autoimmune disease that has
      variable clinical manifestations and morbidity/mortality secondary to organ
      damage due to vasculopathy and/or fibrosis. Initial events in the pathogenesis
      are manifested by fibroproliferative vasculopathy that compromises delivery of
      blood to critical organs. There is evidence of autoimmunity early in the disease
      which persists and is accompanied by fibrotic processes that leave large
      accumulations of collagen and other matrix components in the intima of blood
      vessels and extracellularly in the connective tissue of organs affected by the
      disease. It has recently been realized that the lysophospholipids --
      lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), which are elevated
      in sera of SSc patients, are capable of producing many of the abnormalities
      observed in the vasculature, immune system, and connective tissue of patients
      with this disease. This article reviews key abnormalities of the vasculature,
      immune system, and connective tissue in SSc that could be mediated by LPA/S1P.

PMID- 20807478
TI  - New horizons in speech audiometry?

PMID- 20807479
TI  - A case law review of the individuals with disabilities education act for children
      with hearing loss or auditory processing disorders.
AB  - BACKGROUND: In 1975, Congress passed the Education for All Handicapped Children
      Act (Public Law 94-142), and it has been revised and modified several times. At
      the time of this writing, this law was most recently amended by the Individuals
      with Disabilities Education Improvement Act (Pub. L. No. 108-446, 118 Stat. 2647,
      December 3, 2004), which took effect on July 1, 2005. Colloquially the law is
      still referred to as the Individuals with Disabilities Education Act (IDEA).
      Children with hearing loss or auditory processing disorder (APD) may qualify for
      services under IDEA. However, a review of the literature found no review of case
      law for such children. PURPOSE: This article provides a comprehensive review of
      case law involving the IDEA and children with hearing loss or APD from the U.S.
      Supreme Court and U.S. courts of appeals. RESEARCH DESIGN: We conducted a
      systematic review of case law. A LexisNexis search for cases involving IDEA and
      children with hearing loss or APDs was conducted. For the purpose of the present
      case review, all appellate decisions (cases accepted by the U.S. courts of
      appeals or the U.S. Supreme Court) were included if they found that the child had
      hearing loss or APD, regardless of the reason for the appeal under IDEA. In the
      instance of multiple cases that involved the same two parties, these cases are
      summarized together to provide the legal context. Brief explanations of IDEA and
      the federal judicial process as it pertains to IDEA disputes are presented.
      Following these explanations, a chronological review of IDEA appellate cases
      concerning students with hearing loss or APD is provided. RESULTS: The IDEA cases
      reviewed focus on three main issues: placement of the child, methodology of
      teaching, and the provision of services. CONCLUSIONS: This case law review
      provides a helpful summary of higher court cases for educational audiologists and
      parents of children with hearing loss or APDs, as well as educators,
      individualized education program team members, school administrators, and legal
      representatives involved in IDEA cases.

PMID- 20807480
TI  - Speech perception for adult cochlear implant recipients in a realistic background
      noise: effectiveness of preprocessing strategies and external options for
      improving speech recognition in noise.
AB  - BACKGROUND: Although cochlear implant patients are achieving increasingly higher
      levels of performance, speech perception in noise continues to be problematic.
      The newest generations of implant speech processors are equipped with
      preprocessing and/or external accessories that are purported to improve listening
      in noise. Most speech perception measures in the clinical setting, however, do
      not provide a close approximation to real-world listening environments. PURPOSE:
      To assess speech perception for adult cochlear implant recipients in the presence
      of a realistic restaurant simulation generated by an eight-loudspeaker (R-SPACE)
      array in order to determine whether commercially available preprocessing
      strategies and/or external accessories yield improved sentence recognition in
      noise. RESEARCH DESIGN: Single-subject, repeated-measures design with two groups
      of participants: Advanced Bionics and Cochlear Corporation recipients. STUDY
      SAMPLE: Thirty-four subjects, ranging in age from 18 to 90 yr (mean 54.5 yr),
      participated in this prospective study. Fourteen subjects were Advanced Bionics
      recipients, and 20 subjects were Cochlear Corporation recipients. INTERVENTION:
      Speech reception thresholds (SRTs) in semidiffuse restaurant noise originating
      from an eight-loudspeaker array were assessed with the subjects' preferred
      listening programs as well as with the addition of either Beam preprocessing
      (Cochlear Corporation) or the T-Mic accessory option (Advanced Bionics). DATA
      COLLECTION AND ANALYSIS: In Experiment 1, adaptive SRTs with the Hearing in Noise
      Test sentences were obtained for all 34 subjects. For Cochlear Corporation
      recipients, SRTs were obtained with their preferred everyday listening program as
      well as with the addition of Focus preprocessing. For Advanced Bionics
      recipients, SRTs were obtained with the integrated behind-the-ear (BTE) mic as
      well as with the T-Mic. Statistical analysis using a repeated-measures analysis
      of variance (ANOVA) evaluated the effects of the preprocessing strategy or
      external accessory in reducing the SRT in noise. In addition, a standard t-test
      was run to evaluate effectiveness across manufacturer for improving the SRT in
      noise. In Experiment 2, 16 of the 20 Cochlear Corporation subjects were
      reassessed obtaining an SRT in noise using the manufacturer-suggested "Everyday,"
      "Noise," and "Focus" preprocessing strategies. A repeated-measures ANOVA was
      employed to assess the effects of preprocessing. RESULTS: The primary findings
      were (i) both Noise and Focus preprocessing strategies (Cochlear Corporation)
      significantly improved the SRT in noise as compared to Everyday preprocessing,
      (ii) the T-Mic accessory option (Advanced Bionics) significantly improved the SRT
      as compared to the BTE mic, and (iii) Focus preprocessing and the T-Mic resulted
      in similar degrees of improvement that were not found to be significantly
      different from one another. CONCLUSION: Options available in current cochlear
      implant sound processors are able to significantly improve speech understanding
      in a realistic, semidiffuse noise with both Cochlear Corporation and Advanced
      Bionics systems. For Cochlear Corporation recipients, Focus preprocessing yields
      the best speech-recognition performance in a complex listening environment;
      however, it is recommended that Noise preprocessing be used as the new default
      for everyday listening environments to avoid the need for switching programs
      throughout the day. For Advanced Bionics recipients, the T-Mic offers
      significantly improved performance in noise and is recommended for everyday use
      in all listening environments.

PMID- 20807481
TI  - Auditory brain stem responses evoked by different chirps based on different delay
      models.
AB  - BACKGROUND: A cochlear delay model has previously been proposed for the
      construction of a chirp stimulus in order to compensate for the temporal
      dispersion in the auditory periphery. The large intersubject variability in the
      model data suggests that a chirp constructed from the average model data will not
      be able to compensate equally well for the temporal dispersion in all normal
      hearing subjects. For the recording of the auditory brain stem response (ABR), it
      has been suggested that the most efficient chirp for generating the largest
      response amplitude changes in duration with level, indicating that the delay
      model exhibits a latency change with frequency, which becomes larger at lower
      levels. PURPOSE: To investigate in normal-hearing subjects how the ABR varies in
      response to five different chirps and to study how the efficiency of each chirp
      changes with stimulus level. RESEARCH DESIGN: A click and five chirps of
      different durations and constructed from the proposed delay model were designed
      with identical amplitude spectra. The six stimuli were used to record the ABR
      from 50 normal-hearing test subjects using a quasi-simultaneous stimulation
      technique at 50 and 30 dB nHL. The ABR recordings were evaluated by the peak-to
      trough amplitude and the peak latency. RESULTS: For the test group the following
      level effect was demonstrated: at 50 dB nHL the largest response amplitude was
      provided by a shorter chirp, whereas at 30 dB nHL the largest response amplitude
      was provided by a longer chirp. There is, however, large variability as to which
      of the five chirps generated the largest response in each individual subject, but
      at the two levels of stimulation, the best chirps were significantly correlated
      across the test group. All five chirps generated significantly larger ABRs than
      the click, but at 30 dB nHL the gain in response amplitude by using the chirps
      instead of the click was larger than at 50 dB nHL. CONCLUSIONS: A chirp that
      evokes the largest broadband ABRs in normal-hearing subjects changes in duration
      with level-that is, being relatively short at higher levels (50 dB nHL) and
      relatively long at lower levels and near the threshold. However, the changes in
      amplitude in response to chirps of different durations are not very large, and it
      is therefore uncertain whether the outcome from using such chirps actually would
      outweigh the instrumental complexity of implementation. It appears that the
      largest advantage of using the chirp over the click is found at the lower levels
      of stimulation.

PMID- 20807482
TI  - Effects of acoustical stimuli delivered through hearing aids on tinnitus.
AB  - BACKGROUND: The use of acoustic signals to mask, mix with, or ease the distress
      associated with tinnitus has been clinically employed for decades. It has been
      proposed that expanding acoustic options for tinnitus sufferers due to personal
      preferences is desirable. Fractal tones incorporate many useful characteristics
      of music while avoiding certain features that could be distracting to some
      individuals. PURPOSE: To assess the effects on relaxation, tinnitus annoyance,
      tinnitus handicap, and tinnitus reaction from the use of a hearing aid that
      incorporates combinations of amplification, fractal tones, and white noise.
      RESEARCH DESIGN: Participants listened to experimental hearing aids containing
      several acoustic options and were asked to rate the signals in terms of their
      effect on relaxation and tinnitus annoyance. They subsequently wore the hearing
      aids for 6 mo and completed tinnitus handicap and reaction scales. STUDY SAMPLE:
      Fourteen hearing-impaired adults with primary complaints of subjective tinnitus.
      INTERVENTION: Participants were tested wearing hearing aids containing several
      programs including amplification only, fractal tones only, and a combination of
      amplification, noise, and/or fractal tones. The fractal tones (now commercially
      available as the "Zen" feature) were generated by the Widex Mind hearing aid.
      Rating procedures were conducted in the laboratory, and tinnitus reaction and
      handicap were assessed during and following a 6 mo field trial. DATA COLLECTION
      AND ANALYSIS: Data were collected at the initial visit, one week, 1 mo, 3 mo, and
      6 mo. Nonparametric statistics included Wilcoxon matched-pairs signed-rank,
      chi(2), and repeated-measures analyses of variance. RESULTS: Thirteen of 14
      participants reported that their tinnitus annoyance, as measured by the Tinnitus
      Annoyance Scale, was reduced for at least one of the amplified conditions (with
      or without fractal tones or noise), relative to the unaided condition. Nine
      assigned a lower tinnitus annoyance rating when listening to fractal tones alone
      versus the amplification-alone condition. There was a range of preferences
      observed for fractal settings, with most participants preferring fractals with a
      slow or medium tempo and restricted dynamic range. The majority (86%) indicated
      that it was easier to relax while listening to fractal signals. Participants had
      preferences for certain programs and fractal characteristics. Although seven
      participants rated the noise-only condition as providing the least tinnitus
      annoyance, only two opted to have noise only as a program during the field trial,
      and none selected the noise-only condition as the preferred setting. Furthermore,
      while all four of the experienced hearing aid users selected noise as producing
      the least annoying tinnitus in the laboratory, only one selected it for field
      wear. Tinnitus Handicap Inventory and Tinnitus Reaction Questionnaire scores were
      improved over the course of the 6 mo trial, with clinically significant
      improvements occurring for over half of the participants on at least one of the
      measures. CONCLUSIONS: The results suggest that use of acoustic stimuli,
      particularly fractal tones, delivered though hearing aids can provide
      amplification while allowing for relief for some tinnitus sufferers. It is
      important to recognize, however, that tinnitus management procedures need to be
      supplemented with appropriate counseling.

PMID- 20807483
TI  - Auditory conflict processing: behavioral and electrophysiologic manifestations of
      the stroop effect.
AB  - BACKGROUND: One of the most extensively studied phenomena in cognitive
      neuroscience is the Stroop effect. In an enormous corpus of literature, the
      Stroop task has been used to study conflict processing in the visual modality;
      however, scarce data exist in the auditory modality. PURPOSE: The main goal of
      the present study was to investigate auditory conflict processing by means of
      behavioral and electrophysiologic measures elicited during standard and reversed
      Stroop tasks. A secondary goal was to examine practice-related effects. RESEARCH
      DESIGN: Event-related potentials (ERPs) were recorded from 16 adults during tasks
      requiring classification of word meaning or speaker's gender while ignoring the
      irrelevant (congruent or incongruent) speaker's gender or word meaning,
      respectively. The behavioral measures, reaction time and performance accuracy,
      were simultaneously obtained. RESULTS: Results indicated (1) a significant
      behavioral Stroop effect manifested by prolonged reaction time and reduced
      performance accuracy. In contrast, ERP latencies were unaffected by the
      processing of incongruent versus congruent stimuli, supporting postperceptual
      conflict processing associated with response selection and execution; (2) reduced
      N1 amplitude while processing incongruent versus congruent stimuli; (3) similar
      behavioral Stroop effects in both tasks together with nonsignificant task by
      stimulus type (incongruent, congruent) interactions for N1 and N4; (4)
      significantly prolonged N4 and reaction time together with reduced N1 amplitude
      in the speaker's gender task (to both congruent and incongruent stimuli) compared
      to those found in the word meaning task; and (5) practice-related improvement in
      processing efficacy based on enhanced N1 amplitude, as well as shorter N4 and
      reaction time. CONCLUSIONS: Auditory conflict processing was predominantly
      postperceptual and was located at the response selection and execution stages.
      Alterations in the N1 component, however, provided support for an auditory
      conflict-processing "signature" at the initial stages of the arrival of
      information to the auditory cortex. The current data indicate that speaker's
      gender and word meaning intruded on one another in a similar fashion, supporting
      symmetry between standard and reversed auditory Stroop effects. Nonetheless,
      improved processing efficacy was evident while classifying word meaning.
      Utilization of the present methodology may prove advantageous for studying
      clinical populations exhibiting auditory and/or linguistic processing deficits.

PMID- 20807486
TI  - Outbreak of invasive meningococcal disease in Goleniow County, northwest Poland,
      March 2009.

PMID- 20807487
TI  - Case report: West-Nile virus infection in two Dutch travellers returning from
      Israel.

PMID- 20807488
TI  - Retrospective screening of solid organ donors in Italy, 2009, reveals unpredicted
      circulation of West Nile virus.

PMID- 20807490
TI  - West Nile virus: the need to strengthen preparedness in Europe.

PMID- 20807489
TI  - Ongoing outbreak of West Nile virus infections in humans in Greece, July-August
      2010.

PMID- 20807492
TI  - A young woman with refractory GI symptoms. Adrenal ganglioneuroma.

PMID- 20807491
TI  - A case of cerebral embolism with metastatic chondrosarcoma in the left atrium.
AB  - Cardiac tumor is a rare, but clinically important source of cerebral embolism. We
      report a case of metastatic chondrosarcoma in the left atrium with multiple
      cerebral emboli. A computed tomography scan of the chest revealed a large mass in
      the left atrium and pulmonary vein. The patient underwent heart surgery to remove
      the metastatic chondrosarcoma in the left atrium, to prevent the formation of
      further systemic emboli and possible sudden death. The cardiac tumor resection
      was successful, and the patient was discharged from the hospital without any
      handicap. This is a rare case of metastatic cardiac tumor that was a source of
      emboli into the brain and was eradicated.

PMID- 20807493
TI  - Persistent right-sided chest pain. Esophageal microperforation by a fish bone
      associated with empyema thoracis.

PMID- 20807494
TI  - Influence of long-range contacts and surrounding residues on the transition state
      structures of proteins.
AB  - Understanding the parameters influencing the formation of transition state
      structures in proteins is an important problem in protein folding and kinetics.
      In this work, we have analyzed the structure-based parameters, surrounding
      hydrophobicity, secondary structure, solvent accessibility, number of medium- and
      long-range contacts, and surrounding residues for understanding the transition
      state structures of 15 proteins. The analysis of Phi-values shows that 29% of the
      studied 378 mutants have a Phi-value of more than 0.5. The combination of
      different structure-based parameters could discriminate the residues that have a
      Phi-value cutoff of more than 0.5 with a 5-fold cross-validation accuracy of 68%,
      which indicates that the surrounding residues and contacts play important roles
      in the formation of transition state structures. Systematic analysis on different
      proteins reveals that the proteins azurin, cold shock protein, and C-terminal
      domain of ribosomal protein L9 are influenced by the number of medium- and long
      range proteins, whereas barnase, FK506 binding protein, and IM9 are influenced by
      surrounding residues. The discrimination accuracy lies in the ranges of 81-95%
      and 74-85% for these respective classes of protein. Furthermore, the combination
      of surrounding residues and contacts improved the accuracy up to 24% in other
      considered proteins. We suggest that the structure-based parameters along with
      noncovalent interactions and conservation of residues may aid in identifying the
      potential residues in the formation of transition state structures in proteins.

PMID- 20807495
TI  - Mass spectrometric characterization of the isoforms in Escherichia coli
      recombinant DNA-derived interferon alpha-2b.
AB  - The isoforms Iso-2, Iso-3, and Iso-4 of Escherichia coli-derived recombinant
      human interferon alpha-2b (rhIFN alpha-2b), generated by posttranslational
      modifications of the protein during fermentation, present a major problem in
      terms of purification and the yield of the drug substance. We report here the
      structural characterization of these isoforms by mass spectrometry (MS) methods.
      An extensive MS study was conducted on Iso-4, which is composed of up to 75% of
      the in-process IFN, and on the native rhIFN alpha-2b. The trypsin-digested
      peptide mixtures generated from the two samples were analyzed by liquid
      chromatography (LC)-MS, and targeted peptides were further studied by LC-tandem
      MS (triple quadrupole mass spectrometer), high-resolution MS(n) (LTQ Orbitrap),
      and matrix-assisted laser desorption/ionization MS (MALDI-MS). The structure of
      Iso-4 was elucidated as a novel pyruvic acid ketimine derivative of the N
      terminal cysteine (Cys1) of IFN alpha-2b, where the disulfide bond between Cys1
      and Cys98 was fully reduced and the other disulfide bond pair, Cys29-ss-Cys138,
      was partially reduced. Similarly, Iso-2 was identified as a correctly disulfide
      folded rhIFN alpha-2b with acetylation on Cys1, and Iso-3 was identified as an S
      glutathionylated form (Cys98) of partially reduced rhIFN alpha-2b that was
      pyruvated on Cys1. Based on the characterization work, a reproducible conversion
      procedure was successfully implemented to convert Iso-4 to rhIFN alpha-2b.

PMID- 20807496
TI  - Detection of protein kinase substrates in tissue extracts after separation by
      isoelectric focusing.
AB  - Here we report a simple and useful method to detect endogenous substrates of
      protein kinases. When crude tissue extracts were resolved by liquid-phase
      isoelectric focusing (MicroRotofor) and the separated protein fractions were
      phosphorylated by protein kinases such as Ca(2+)/calmodulin-dependent protein
      kinase I or cAMP-dependent protein kinase, various proteins in the different
      fractions were efficiently phosphorylated. Since a higher number of substrates
      could significantly be detected using the resolved fractions by MicroRotofor as
      compared to direct analysis of the original tissue extracts, our present method
      will be applicable to the screening of endogenous substrates for various protein
      kinases.

PMID- 20807498
TI  - Quantification of protein calibrants by amino acid analysis using isotope
      dilution mass spectrometry.
AB  - This work demonstrates that amino acid analysis based on isotope dilution mass
      spectrometry (IDMS) can be applied to quantify proteins having different
      complexities and natures. Five proteins and one decapeptide were selected for the
      study: C-reactive protein (CRP), beta-2-microglobulin (B2M), cystatine C (CysC),
      human serum albumin (HSA), Ara h1, and angiotensin I. The quantification was
      based on the determination of four amino acids, proline (Pro), isoleucine (Ile),
      valine (Val), and phenylalanine (Phe) within a working range between 5 and 100
      pmol/injection of each amino acid, after 60 min digestion with HCl at 150 degrees
      C. The amino acids were selected taking into account their abundance in the
      protein sequence and to include the more difficult to break peptide bonds.
      Quantification of the protein amounts calculated from each amino acid is
      consistent, indicating that the method is working reliably. This consistency
      points to a complete hydrolysis of the proteins. The trueness of the method was
      proven when dry mass determination after dialysis was applied to HSA and CRP and
      the results were compared to those from amino acid analysis. Traceability to SI
      was assured by extensive characterisation of the amino acid calibrants by nuclear
      magnetic resonance, neutron activation analysis, and Karl Fischer titration.

PMID- 20807497
TI  - A magnetic bead-based protein kinase assay with dual detection techniques.
AB  - A novel magnetic bead-based protein kinase assay was developed using MALDI-TOF
      mass spectrometry (MALDI-TOF MS) and immunochemifluorescence as two independent
      detection techniques. Abltide substrate was immobilized onto magnetic beads via
      noncovalent biotin-streptavidin interactions. This noncovalent immobilization
      strategy facilitated peptide release and allowed MALDI-TOF MS analysis of
      substrate phosphorylation. The use of magnetic beads provided rapid sample
      handling and allowed secondary analysis by immunochemifluorescence to determine
      the degree of substrate phosphorylation. This dual detection technique was used
      to evaluate the inhibition of c-Abl kinase by imatinib and dasatinib. For each
      inhibitor, IC50 (half-maximal inhibitory concentration) values determined by
      these two different detection methods were consistent and close to values
      reported in the literature. The high-throughput potential of this new approach to
      kinase assays was preliminarily demonstrated by screening a chemical library
      consisting of 31 compounds against c-Abl kinase using a 96-well plate. In this
      proof-of-principle experiment, both MALDI-TOF MS and immunochemifluorescence were
      able to compare inhibitor potencies with consistent values. Dual detection may
      significantly enhance the reliability of chemical library screening and identify
      false positives and negatives. Formatted for 96-well plates and with high
      throughput potential, this dual detection kinase assay may provide a rapid,
      reliable, and inexpensive route to the discovery of small-molecule drug leads.

PMID- 20807499
TI  - On the association of lipid rafts to the spectrin skeleton in human erythrocytes.
AB  - Lipid rafts are local inhomogeneities in the composition of the plasma membrane
      of living cells, that are enriched in sphingolipids and cholesterol in a liquid
      ordered state, and proteins involved in receptor-mediated signalling.
      Interactions between lipid rafts and the cytoskeleton have been observed in
      various cell types. They are isolated as a fraction of the plasma membrane that
      resists solubilization by nonionic detergents at 4 degrees C (detergent-resistant
      membranes, DRMs). We have previously described that DRMs are anchored to the
      spectrin-based membrane skeleton in human erythrocytes and can be released by
      increasing the pH and ionic strength of the solubilization medium with sodium
      carbonate. It was unexplained why this carbonate treatment was necessary and why
      this requirement was not reported by other workers in this area. We show here
      that when contaminating leukocytes are present in erythrocyte preparations that
      are subjected to detergent treatment, the isolation of DRMs can occur without the
      requirement for carbonate treatment. This is due to the uncontrolled breakdown of
      erythrocyte membrane components by hydrolases that are released from
      contaminating neutrophils that lead to proteolytic disruption of the
      supramolecular assembly of the membrane skeleton. Results presented here
      corroborate the concept that DRMs are anchored to the membrane skeleton through
      electrostatic interactions that most likely involve the spectrin molecule.

PMID- 20807500
TI  - Migration defects by DISC1 knockdown in C57BL/6, 129X1/SvJ, and ICR strains via
      in utero gene transfer and virus-mediated RNAi.
AB  - Disrupted-in-Schizophrenia 1 (DISC1) is a promising genetic risk factor for major
      mental disorders. Many groups repeatedly reported a role for DISC1 in brain
      development in various strains of mice and rats by using RNA interference (RNAi)
      approach. Nonetheless, due to the complexity of its molecular disposition, such
      as many splice variants and a spontaneous deletion in a coding exon of the DISC1
      gene in some mouse strains, there have been debates on the interpretation on
      these published data. Thus, in this study, we address this question by DISC1
      knockdown via short-hairpin RNAs (shRNAs) against several distinct target
      sequences with more than one delivery methodologies into several mouse strains,
      including C57BL/6, ICR, and 129X1/SvJ. Here, we show that DISC1 knockdown by in
      utero electroporation of shRNA against exons 2, 6, and 10 consistently results in
      neuronal migration defects in the developing cerebral cortex, which are
      successfully rescued by co-expression of full-length DISC1. Furthermore,
      lentivirus-mediated shRNA also led to migration defects, which is consistent with
      two other methodologies already published, such as plasmid-mediated and
      retrovirus-mediated ones. The previous study by Song's group also reported that,
      in the adult hippocampus, the phenotype elicited by DISC1 knockdown with shRNA
      targeting exon 2 was consistently seen in both C57BL/6 and 129S6 mice. Taken
      together, we propose that some of DISC1 isoforms that are feasible to be knocked
      down by shRNAs to exon 2, 6, and 10 of the DISC1 gene play a key role for
      neuronal migration commonly in various mouse strains and rats.

PMID- 20807501
TI  - The role of iron in the proliferation of Drosophila l(2) mbn cells.
AB  - Iron is essential for life and is needed for cell proliferation and cell cycle
      progression. Iron deprivation results first in cell cycle arrest and then in
      apoptosis. The Drosophila tumorous larval hemocyte cell line l(2) mbn was used to
      study the sensitivity and cellular response to iron deprivation through the
      chelator desferrioxamine (DFO). At a concentration of 10 MUM DFO or more the
      proliferation was inhibited reversibly, while the amount of dead cells did not
      increase. FACS analysis showed that the cell cycle was arrested in G1/S-phase and
      the transcript level of cycE was decreased to less than 50% of control cells.
      These results show that iron chelation in this insect tumorous cell line causes a
      specific and coordinated cell cycle arrest.

PMID- 20807502
TI  - Inhibitory Smad proteins promote the differentiation of mouse embryonic stem
      cells into ependymal-like ciliated cells.
AB  - Motile cilia play crucial roles in the maintenance of homeostasis in vivo.
      Defects in the biosynthesis of cilia cause immotile cilia syndrome, also known as
      primary ciliary dyskinesia (PCD), which is associated with a variety of complex
      diseases. In this study, we found that inhibitory Smad proteins, Smad7 and Smad6,
      significantly promoted the differentiation of mouse embryonic stem (ES) cells
      into ciliated cells. Moreover, these Smad proteins specifically induced
      morphologically distinct Musashi1-positive ciliated cells. These results suggest
      that inhibitory Smad proteins could be important regulators not only for the
      regulation of ciliated cell differentiation, but also for the subtype
      specification of ciliated cells during differentiation from mouse ES cells.

PMID- 20807503
TI  - Sox2 regulatory region 2 sequence works as a DNA nuclear targeting sequence
      enhancing the efficiency of an exogenous gene expression in ES cells.
AB  - In this report, the effects of two DNA nuclear targeting sequence (DTS)
      candidates on the gene expression efficiency in ES cells were investigated.
      Reporter plasmids containing the simian virus 40 (SV40) promoter/enhancer
      sequence (SV40-DTS), a DTS for various types of cells but not being reported yet
      for ES cells, and the 81 base pairs of Sox2 regulatory region 2 (SRR2) where two
      transcriptional factors in ES cells, Oct3/4 and Sox2, are bound (SRR2-DTS), were
      introduced into cytoplasm in living cells by femtoinjection. The gene expression
      efficiencies of each plasmid in mouse insulinoma cell line MIN6 cells and mouse
      ES cells were then evaluated. Plasmids including SV40-DTS and SRR2-DTS exhibited
      higher gene expression efficiency comparing to plasmids without these DTSs, and
      thus it was concluded that both sequences work as a DTS in ES cells. In addition,
      it was suggested that SRR2-DTS works as an ES cell-specific DTS. To the best of
      our knowledge, this is the first report to confirm the function of DTSs in ES
      cells.

PMID- 20807504
TI  - Potent in vivo suppression of inflammation by selectively targeting the high
      affinity conformation of integrin alpha4beta1.
AB  - The development of antagonists to the alpha4 integrin family of cell adhesion
      molecules has been an active area of pharmaceutical research to treat
      inflammatory and autoimmune diseases. Presently being tested in human clinical
      trials are compounds selective for alpha4beta1 (VLA-4) as well as several dual
      antagonists that inhibit both alpha4beta1 and alpha4beta7. The value of a dual
      versus a selective small molecule antagonist as well as the consequences of
      inhibiting different affinity states of the alpha4 integrins have been debated in
      the literature. Here, we characterize TBC3486, a N,N-disubstituted amide, which
      represents a unique structural class of non-peptidic, small molecule VLA-4
      antagonists. Using a variety of adhesion assay formats as well as flow cytometry
      experiments using mAbs specific for certain activation-dependent integrin
      epitopes we demonstrate that TBC3486 preferentially targets the high affinity
      conformation of alpha4beta1 and behaves as a ligand mimetic. The antagonist is
      capable of blocking integrin-dependent T-cell co-activation in vitro as well as
      proves to be efficacious in vivo at low doses in two animal models of allergic
      inflammation. These data suggest that a small molecule alpha4 integrin antagonist
      selective for alpha4beta1 over alpha4beta7 and, specifically, selective for the
      high affinity conformation of alpha4beta1 may prove to be an effective therapy
      for multiple inflammatory diseases in humans.

PMID- 20807505
TI  - Zinc finger-zinc finger interaction between the transcription factors, GATA-1 and
      Sp1.
AB  - In contrast to the extensive understanding of the zinc finger-DNA interactions,
      less is known about zinc finger-zinc finger interactions. GATA-1 and Sp1 are
      transcription factors with zinc finger domains for DNA binding. The interaction
      between the GATA-1 and Sp1 zinc finger domains is important for synergistic
      transcriptional effects in erythroid genes. Despite the biological importance of
      the GATA-1 and Sp1 interaction, the molecular mechanism of the interaction
      remains unclear. We constructed a series of deletion mutants of the zinc finger
      domains of GATA-1 and Sp1 to identify the regions within the GATA-1 and Sp1 zinc
      finger domains that interact. The zinc finger-zinc finger interaction modes were
      also estimated from calorimetric measurements. This revealed that the interaction
      between the Sp1 and GATA-1 zinc finger domains was primarily electrostatic, and
      that the linker region of the Sp1 zinc fingers is important for the association
      with the GATA-1 zinc finger domains. We propose a new molecular mechanism for
      zinc finger-zinc finger interactions that should contribute to our understanding
      of the bio-functional role of the interaction between GATA-1 and Sp1.

PMID- 20807506
TI  - Ursodeoxycholic acid modulates the ubiquitin-proteasome degradation pathway of
      p53.
AB  - p53/Mdm-2 interaction is a prime target of ursodeoxycholic acid (UDCA) for
      regulating apoptosis in primary rat hepatocytes. Here, we further explored the
      role of UDCA in downregulating p53 by Mdm-2. UDCA reduced the stability of p53 by
      decreasing protein half-life. Although proteasomal activity was slightly
      increased with UDCA, the effect was also observed for other bile acids. More
      importantly, immunoprecipitation assays revealed that UDCA promoted p53
      ubiquitination, therefore leading to increased p53 degradation. In this regard,
      proteasome inhibition after UDCA pre-treatment resulted in accumulation of
      ubiquitinated p53, which in turn was prevented in cells overexpressing a mutated
      form of p53 that does not undergo Mdm-2 ubiquitination. The involvement of Mdm-2
      in UDCA-mediated response was further confirmed by siRNA-mediated gene silencing
      experiments. Finally, the protective effect of UDCA against p53-induced apoptosis
      was abolished after inhibition of proteasome activity and prevention of p53
      ubiquitination by Mdm-2. These findings suggest that UDCA protects cells from p53
      mediated apoptosis by promoting its degradation via the Mdm-2-ubiquitin
      proteasome pathway.

PMID- 20807507
TI  - Transmission of circulating cell-free AA amyloid oligomers in exosomes vectors
      via a prion-like mechanism.
AB  - Recent studies clearly demonstrated that several types of pathogenic amyloid
      proteins acted as agents that could transmit amyloidosis by means of a prion-like
      mechanism. Systemic AA amyloidosis is one of the most severe complications of
      chronic inflammatory disorders, particularly rheumatoid arthritis. It is well
      known that, similar to an infectious prion protein, amyloid-enhancing factor
      (AEF) acts as a transmissible agent in AA amyloidosis. However, how AEF transmits
      AA amyloidosis in vivo remained to be fully elucidated. In the present study, we
      focused on finding cell-free forms of AEF and its carriers in circulation by
      using the murine transfer model of AA amyloidosis. We first determined that
      circulating cell-free AEF existed in blood and plasma in mice with systemic AA
      amyloidosis. Second, we established that plasma exosomes containing AA amyloid
      oligomers derived from serum amyloid A had AEF activity and could transmit
      systemic AA amyloidosis via a prion-like mechanism. These novel findings should
      provide insights into the transmission mechanism of systemic amyloidoses.

PMID- 20807508
TI  - Pyruvate carboxylase is expressed in human skeletal muscle.
AB  - Pyruvate carboxylase (PC) is a mitochondrial enzyme that catalyses the
      carboxylation of pyruvate to oxaloacetate thereby allowing supplementation of
      citric acid cycle intermediates. The presence of PC in skeletal muscle is
      controversial. We report here, that PC protein is easily detectable by
      streptavidin blot and describe the presence of considerable amounts of PC in
      cultured human myotubes and in human muscle tissue.

PMID- 20807509
TI  - Non-canonical ubiquitylation of the proneural protein Ngn2 occurs in both Xenopus
      embryos and mammalian cells.
AB  - Poly-ubiquitin chains targeting proteins for 26S proteasomal degradation are
      classically anchored on internal lysines of substrates via iso-peptide linkages.
      However recently, linkage of ubiquitin moieties to non-canonical nucleophilic
      residues, such as cysteines, serines and threonines, has been demonstrated in a
      small number of cases. Non-canonical ubiquitylation of the proneural protein Ngn2
      has previously been seen in Xenopus egg extract, but it was not clear whether
      such highly unusual modes of ubiquitylation were restricted to the environment of
      egg cytoplasm. Here we show that Ngn2 is, indeed, ubiquitylated on non-canonical
      sites in extracts from neurula stage Xenopus embryos, when Ngn2 is usually
      active. Moreover, in the P19 mammalian embryonal carcinoma cell line capable of
      differentiating into neurons, xNgn2 is ubiquitylated on both canonical and non
      canonical sites. We see that mutation of cysteines alone results stabilisation of
      the protein in P19 cells, indicating that non-canonical ubiquitylation on these
      residues normally contributes to the fast turnover of xNgn2 in mammalian cells.

PMID- 20807510
TI  - Efficient production and purification of functional bacteriorhodopsin with a
      wheat-germ cell-free system and a combination of Fos-choline and CHAPS
      detergents.
AB  - Cell-free translation is one potential approach to the production of functional
      transmembrane proteins. We have now examined various detergents as supplements to
      a wheat-germ cell-free system in order to optimize the production and subsequent
      purification of a functional model transmembrane protein, bacteriorhodopsin. We
      found that Fos-choline and CHAPS detergents counteracted each other's inhibitory
      effects on cell-free translation activity and thereby allowed the efficient
      production and subsequent purification of functional bacteriorhodopsin in high
      yield.

PMID- 20807511
TI  - Testosterone regulation of Alzheimer-like neuropathology in male 3xTg-AD mice
      involves both estrogen and androgen pathways.
AB  - Normal, age-related depletion of the androgen testosterone is a risk factor for
      Alzheimer's disease (AD) in men. Previously, we reported that experimental
      androgen depletion significantly accelerates development of AD-like
      neuropathology in the 3xTg-AD triple-transgenic mouse model of AD, an effect
      prevented by androgen treatment. Because testosterone is metabolized in brain
      into both the androgen dihydrotestosterone (DHT) and the estrogen 17beta
      estradiol (E2), testosterone can mediate its effects through androgen and or
      estrogen pathways. To define the role of androgen and estrogen pathways in
      regulation of AD-like neuropathology, we compared the effects of testosterone (T)
      and its metabolites DHT and E2 in male 3xTg-AD mice depleted of endogenous sex
      steroid hormones by gonadectomy (GDX). Male 3xTg-AD mice were sham GDX or GDX,
      immediately treated with vehicle, T, DHT, or E2, and 4 months later evaluated for
      two indices of AD-like neuropathology, beta-amyloid (Abeta) accumulation and tau
      hyperphosphorylation. In comparison to sham GDX mice, we observed a significant
      increase in Abeta accumulation in GDX mice in subiculum, hippocampus, and
      amygdala. Treatment of GDX mice with T prevented the increased Abeta accumulation
      in all three brain regions. DHT treatment yielded similar results, significantly
      reducing Abeta accumulation across brain regions. Interestingly, E2 prevented
      Abeta accumulation in hippocampus but exerted only partial effects in subiculum
      and amygdala. Levels of tau hyperphosphorylation in sham GDX male 3xTg-AD mice
      were modest and only slightly increased by GDX. Treatment of GDX mice with T or
      E2 but not DHT reduced tau hyperphosphorylation to levels lower than observed in
      sham animals. These data suggest that testosterone regulates Abeta pathology
      through androgen and estrogen pathways and reduces tau pathology largely through
      estrogen pathways. These findings further define hormone pathways involved in
      regulation of AD-related pathology, information that is important for
      understanding disease etiology and developing pathway-specific hormone
      interventions.

PMID- 20807512
TI  - Estrogen signaling in hypothalamic circuits controlling reproduction.
AB  - It is well known that many of the actions of 17beta-estradiol (E2) in the central
      nervous system are mediated via intracellular receptor/transcription factors that
      interact with steroid response elements on target genes. However, there is
      compelling evidence for membrane steroid receptors for estrogen in hypothalamic
      and other brain neurons. Yet, it is not well understood how estrogen signals via
      membrane receptors and how these signals impact not only membrane excitability
      but also gene transcription in neurons that modulate GnRH neuronal excitability.
      Indeed, it has been known for some time that E2 can rapidly alter neuronal
      activity within seconds, indicating that some cellular effects can occur via
      membrane delimited events. In addition, E2 can affect second messenger systems
      including calcium mobilization and a plethora of kinases to alter cell signaling.
      Therefore, this review will consider our current knowledge of rapid membrane
      initiated and intracellular signaling by E2 in hypothalamic neurons critical for
      reproductive function.

PMID- 20807513
TI  - Signal enhancement and suppression during visual-spatial selective attention.
AB  - Selective attention involves the relative enhancement of relevant versus
      irrelevant stimuli. However, whether this relative enhancement involves primarily
      enhancement of attended stimuli, or suppression of irrelevant stimuli, remains
      controversial. Moreover, if both enhancement and suppression are involved,
      whether they result from a single mechanism or separate mechanisms during
      attentional control or selection is not known. In two experiments using a spatial
      cuing paradigm with task-relevant targets and irrelevant distractors, target, and
      distractor processing was examined as a function of distractor expectancy.
      Additionally, in the second study the interaction of perceptual load and
      distractor expectancy was explored. In both experiments, distractors were either
      validly cued (70%) or invalidly cued (30%) in order to examine the effects of
      distractor expectancy on attentional control as well as target and distractor
      processing. The effects of distractor expectancy were assessed using event
      related potentials recorded during the cue-to-target period (preparatory
      attention) and in response to the task-relevant target stimuli (selective
      stimulus processing). Analyses of distractor-present displays (anticipated versus
      unanticipated), showed modulations in brain activity during both the preparatory
      period and during target processing. The pattern of brain responses suggest both
      facilitation of attended targets and suppression of unattended distractors. These
      findings provide evidence for a two-process model of visual-spatial selective
      attention, where one mechanism (facilitation) influences relevant stimuli and
      another (suppression) acts to filter distracting stimuli.

PMID- 20807514
TI  - Glutamate regulation of GnRH neuron excitability.
AB  - The gonadotropin-releasing hormone (GnRH) neuronal network is the master
      controller of the reproductive axis. It is widely accepted that the amino acid
      transmitters GABA and glutamate play important roles in controlling GnRH neuron
      excitability. However, remarkably few studies have examined the functional role
      of direct glutamate regulation of GnRH neurons. Dual-labeling investigations have
      shown that GnRH neurons express receptor subunits required for AMPA, NMDA and
      kainate signaling in a heterogeneous manner. Electrophysiological and calcium
      imaging studies have confirmed this heterogeneity and shown that while the
      majority of adult GnRH neurons express AMPA/kainate receptors, only small sub
      populations have functional NMDA or metabotropic glutamate receptors.
      Accumulating evidence suggests that one important role of direct glutamate
      signaling at GnRH neurons is for their activation at the time of puberty. Whereas
      in vivo studies have indicated the importance of NMDA signaling within the whole
      of the GnRH neuronal network, including afferent neurons and glia, investigations
      at the level of the GnRH neuron suggest that peripubertal changes in AMPA
      receptor expression may be dominant in the mouse. The sources of glutamatergic
      inputs to the GnRH neurons are only just beginning to be examined and include the
      anteroventral periventricular nucleus as well as the possibility that GnRH
      neurons may use glutamate as a neurotransmitter in recurrent collateral
      innervation. It is expected that a full understanding of the glutamatergic
      regulation of GnRH neurons will provide significant insight into the mechanisms
      underlying their control of reproductive function.

PMID- 20807515
TI  - Progressive loss of dopaminergic neurons induced by unilateral rotenone infusion
      into the medial forebrain bundle.
AB  - Rotenone, a mitochondrial complex 1 inhibitor, causes oxidative damage via
      production of reactive oxygen species. We examined the pathophysiology of
      neuronal and glial cells of the nigrostriatal pathway following unilateral
      infusion of varying doses of rotenone into the substantia nigra or medial
      forebrain bundle of adult male Sprague-Dawley rats, sacrificed 14 and 60 days
      after infusion. Immunofluorescence techniques were used to qualitatively and
      quantitatively assay dopaminergic neurons, their projections, glial cells,
      synapses, and oxidative stress. Rotenone infusion into the substantia nigra at
      all concentrations caused extensive damage and tissue necrosis, therefore of
      limited relevance for producing a Parkinson disease model. Infusion of 0.5MUg of
      rotenone targeting the medial forebrain bundle induced oxidative stress in
      dopaminergic neurons causing ongoing cell stress as defined by an elevation of
      stress granule and oxidative stress markers. This treatment resulted in the loss
      of tyrosine hydroxylase immunoreactive cells in the substantia nigra (p<=0.01)
      and loss of tyrosine hydroxylase immunoreactive nerve fibres and synaptic
      specialisations in the striatum (p<=0.01). The infusion of 0.5MUg of rotenone
      also caused an increase in astrocytes and microglial cells in the substantia
      nigra in comparison to control (p<=0.01). We examined the time-dependent
      reduction of tyrosine hydroxylase-positive nerve fibres and cell bodies in the
      striatum and substantia nigra respectively, with a progressive reduction evident
      60days after infusion (p<=0.01, p<=0.05). Dopaminergic axons exposed to low-dose
      rotenone undergo oxidative stress, with a resultant ongoing loss of dopaminergic
      neurons, providing an animal model relevant to Parkinson disease.

PMID- 20807516
TI  - Effect of L-NAME microinjected into the nucleus tractus solitarius on jejunal
      glucose and electrolyte absorption in anesthetized rats.
AB  - The aim of the present study was to investigate the effects of N(G)-nitro-L
      arginine-methyl-ester (L-NAME) microinjected into the rostral nucleus tractus
      solitarius (NTS) on jejunal glucose, sodium and potassium absorption. Male Wistar
      rats (210-250 g, n=6-12) were anesthetized and submitted to midline laparotomy to
      expose and isolate 20 cm of jejunal loop and perform a subdiaphragmatic truncal
      vagotomy or sympathectomy. Either 0.9% NaCl or L-NAME (10 nmol 100 nl-1) was
      microinjected into the rostral NTS using a stereotaxic instrument. Tyrode
      solution (pH 8) containing twice the usual concentrations of glucose, sodium and
      potassium was infused (0.5 ml min-1) into the jejunal loop and samples were taken
      at 10-min intervals during the 40-min experiment. Results were expressed by the
      difference between influx and efflux. L-NAME into the NTS increased glucose
      absorption and decreased potassium absorption when compared to the saline group
      (38.8 +/- 3.8 vs. 50.3 +/- 3.3 mg/dl and 0.6+/-0.01 vs. 0.4 +/- 0.03 mM,
      respectively; p<0.05). Sympathectomy inhibited the glucose absorption caused by L
      NAME alone (50.3 +/- 3.3 vs. 30.7 +/- 4.6 mg/dl; p<0.05), whereas vagotomy
      inhibited the L-NAME effect on potassium absorption (0.40 +/- 0.02 vs. 0.70 +/-
      0.05; p<0.05). Moreover, increased sodium absorption was observed only in the
      group that received 30 nmol of L-NAME into NTS (33.0 +/- 4.2 vs. 48.4 +/- 3.9).
      In conclusion, the results suggest the participation of endogenous nitric oxide
      (NO) in the NTS in modulating intestinal glucose and potassium absorption
      mediated by the autonomic nervous system.

PMID- 20807517
TI  - An okadaic acid-induced model of tauopathy and cognitive deficiency.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease that causes
      cognitive and behavioral deterioration in the elderly. Neurofibrillary tangles
      (NFTs) are one of the pathological hallmarks of AD that has been shown to
      correlate positively with the severity of dementia in the neocortex of AD
      patients. In an attempt to characterize an in vivo AD tauopathy model, okadaic
      acid (OA), a protein phosphatase inhibitor, was microinfused into the right
      lateral dorsal hippocampus area of ovariectomized adult rat. Cognitive deficiency
      was seen in OA-treated rats without a change in motor function. Both silver
      staining and immunohistochemistry staining revealed that OA treatment induces
      NFTs-like conformational changes in both the cortex and hippocampus.
      Phosphorylated tau as well as cyclin-dependent kinase 5 (cdk5) and its
      coactivator, p25, were significantly increased in these regions of the brain.
      Oxidative stress was also increased with OA treatment as measured by protein
      carbonylation and lipid peroxidation. These data suggest that the unilateral
      microinfusion of OA into the dorsal hippocampus causes cognitive deficiency, NFTs
      like pathological changes, and oxidative stress as seen in AD pathology via tau
      hyperphosphorylation caused by inhibition of protein phosphatases.

PMID- 20807518
TI  - AT1 angiotensin II receptor and novel non-AT1, non-AT2 angiotensin II/III binding
      site in brainstem cardiovascular regulatory centers of the spontaneously
      hypertensive rat.
AB  - Spontaneously hypertensive rats (SHR) have an activated brain angiotensin system
      that contributes to the elevation of blood pressure in this animal model.
      Physiological and pharmacological studies suggest that hyperactivation of brain
      AT1 angiotensin receptors is a major pathophysiological factor. Consistent with
      these observations, radioligand binding studies indicate widespread up-regulation
      of brain angiotensin receptors in SHR. One key brainstem site in which AT1
      receptor stimulation appears to contribute to the elevated blood pressure in SHR
      is the rostral ventrolateral medulla (RVLM). However, no quantitative comparison
      of AT1 receptor binding in the RVLM has been made in SHR versus normotensive
      rats. A novel, non-AT1, non-AT2 binding site, specific for angiotensins II and
      III, has recently been discovered in the brain. To determine if radioligand
      binding to either AT1 receptors or this novel angiotensin binding site is altered
      in the RVLM and other caudal brainstem regions of SHR, a quantitative
      densitometric autoradiographic comparison of radioligand binding in SHR versus
      normotensive Wistar-Kyoto rats was made. In both the RVLM and caudal
      ventrolateral medulla (CVLM) as well as dorsomedial medulla (DMM), there was
      increased expression of AT1 receptor binding in SHR (13%, 9%, and 23%,
      respectively). Conversely, expression of the novel, non-AT1, non-AT2, angiotensin
      II and III binding site was decreased in the RVLM and DMM of SHR (37% and 13%,
      respectively). This increased AT1 receptor binding in the RVLM may contribute to
      the hypertension of SHR. Reduced radioligand binding to the novel, non-AT1, non
      AT2, angiotensin binding site in the RVLM of SHR may indicate a role for this
      binding site to reduce blood pressure via its interactions with angiotensins II
      and III.

PMID- 20807520
TI  - ZC3H12A (MCPIP1): molecular characteristics and clinical implications.
AB  - BACKGROUND: ZC3H12A is a gene whose absence is related to autoimmune disorders
      and to other phenotypical alterations. METHODS: A comprehensive review of the
      structure, molecular functions and regulation of ZC3H12A gene and its protein
      MCPIP1 is done in order to understand their clinical implications. RESULTS:
      ZC3H12A, at 1p34.3, has 9860bp, six exons and 61 described SNPs. Eleven are non
      synonymous thus leading to changes in MCPIP1, the protein encoded by ZC3H12A.
      MCPIP1 is induced by MCP-1 and IL-1 whose signals are transduced through the NF
      kbeta and MAPkinase pathways. This protein acts as an RNAse by degrading
      chemokine transcripts such as IL-1 as well as its own mRNA and as a transcription
      factor by reducing the expression of other chemokines induced by NF-kbeta such as
      MCP-1. It also up-regulates genes involved in several differentiation processes
      and apoptosis. Therefore, ZC3H12A is an equilibrium gatekeeper that not only
      regulates its own inducers but also controls the regulation by degrading its own
      mRNA. CONCLUSION: Understanding ZC3H12A gives a comprehensive panorama that
      promises to improve our understanding of processes in which this gene is involved
      including autoimmune, infectious and cardiovascular diseases.

PMID- 20807521
TI  - Caspase-cleaved fragments of cytokeratin 18 in patients with chronic hepatitis B.
AB  - BACKGROUND: During hepatocyte apoptosis, intermediate filament protein
      cytokeratin 18 is cleaved by caspases at Asp396 which can be specifically
      detected by the monoclonal antibody M30 (M30-antigen). In this study, we sought
      to determine whether serum M30-antigen levels can serve as a useful biomarker of
      liver injury in the clinical spectrum of HBV infection. METHODS: Serum M30
      antigen levels were measured in inactive HBV carriers (n=54), patients with HBeAg
      negative chronic hepatitis B (CHB, n=47), patients with HBeAg-positive CHB (n=42)
      and healthy controls (n=29). All subjects were treatment-naive. RESULTS: There
      were significant differences in serum M30-antigen levels across the study groups
      (P<0.001; Kruskal-Wallis test). Post hoc analyses revealed that M30-antigen
      levels did not differ significantly between inactive HBV carriers (median 109.6
      U/L) and healthy controls (median 106.1 U/L). However, both patients with HBeAg
      negative (CHB, median 182.9 U/L, P<0.001) and HBeAg-positive CHB (median 158.3
      U/L, P<0.001) had significantly higher levels of M30-antigen compared with
      inactive HBV carriers. CONCLUSIONS: Hepatocyte apoptotic activity--as reflected
      by serum M30-antigen levels--is increased in chronic active hepatitis B, but is
      not associated with the HBeAg status. In contrast, apoptosis does not appear to
      be a prominent feature of inactive HBV carriers.

PMID- 20807519
TI  - Attenuation of cannabinoid-induced inhibition of medullary dorsal horn neurons by
      a kappa-opioid receptor antagonist.
AB  - The kappa-opioid receptor (KOR) antagonist norbinaltorphimine (nor-BNI)
      attenuates behavioral antinociception produced by spinal administration of the
      cannabinoid receptor agonist delta-9-tetrahydorcannabinol (THC). The present
      study examined the ability of nor-BNI to prevent cannabinoid-induced inhibition
      of medullary dorsal horn (MDH) nociceptive neurons and antinociception produced
      by the cannabinoid agonist WIN 55,212-2 (WIN-2). Extracellular, single-unit
      recordings of lamina I and lamina V MDH neurons were performed in urethane
      anesthetized rats. Heat-evoked activity was measured before and after local
      brainstem application of nor-BNI or vehicle followed by WIN-2. In both lamina I
      and lamina V neurons, prior application of nor-BNI prevented the inhibition of
      heat-evoked activity by WIN-2. In separate experiments, the contribution of KOR
      to cannabinoid-induced increases in heat-evoked head withdrawal latencies was
      assessed in lightly urethane-anesthetized rats. Antinociception produced by
      intrathecal administration of WIN-2 and THC was attenuated by prior
      administration of nor-BNI. In contrast, antinociception produced by the
      cannabinoid CP55940 remained unaffected by prior administration of nor-BNI. These
      results indicate that cannabinoid inhibition of nociceptive reflexes produced by
      WIN-2 and THC may result from inhibition of dorsal horn neurons through a KOR
      dependent mechanism.

PMID- 20807522
TI  - Maternal isovaleric acidemia: observation of distinctive changes in plasma amino
      acids and carnitine profiles during pregnancy.
AB  - BACKGROUND: Tandem mass spectrometry based newborn screening programs (NBS) allow
      early diagnosis and treatment for a number of inborn metabolic disorders. Despite
      the improved prognosis of affected individuals, the knowledge regarding the
      potential risks of childbearing in many of these conditions remains limited.
      Newborns with isovaleric acidemia (IVA) have been diagnosed by NBS and most of
      them can thrive and develop normally. Many affected individuals will therefore
      reach childbearing age in the near future. The information about maternal IVA,
      however, is quite limited. CASE REPORT: Close observation of plasma amino acid,
      carnitine, and acylcarnitine profiles was performed in a patient with IVA that
      completed uneventful pregnancy. Plasma isovalerylcarnitine level was drastically
      decreased from the second trimester and free carnitine was inversely increased,
      suggesting reduced production of isovaleryl-CoA. This decrease of isovaleryl-CoA
      production was likely due to reduced leucine metabolism, secondary to the
      enhanced fetal anabolism associated with the rapid fetal growth of the second and
      the third trimesters. A decrease in maternal essential amino acids, including
      leucine was observed during the second and the third trimesters. CONCLUSION: This
      observation revealed distinctive metabolic profiles during pregnancy in a patient
      with IVA and supports close laboratory monitoring and diet management for
      successful pregnancy.

PMID- 20807523
TI  - A new approach to imprinting mutation detection in GNAS by Sequenom EpiTYPER
      system.
AB  - BACKGROUND: Pseudohypoparathyroidism type Ib (PHPIb) results from abnormal
      imprinting of GNAS. Familial and sporadic forms of PHPIb have distinct GNAS
      imprinting patterns: familial PHPIb patients have an exon A/B-only imprinting
      defect and an intragenic STX16 deletion, whereas sporadic PHPIb cases have
      abnormal imprinting of the three differentially methylated regions (DMRs) in GNAS
      without the STX16 deletion. Overall GNAS methylation defects have recently been
      detected in some PHPIa patients. METHODS: This study describes the first
      quantitative methylation analysis of multiple CpG sites for three different GNAS
      DMRs using the Sequenom EpiTYPER in 35 controls, 12 PHPIb patients, 2 PHPIa
      patients and 2 patients without parathormone (PTH) resistance but having only
      hypocalcemia and hyperphosphatemia. RESULTS: All patients have GNAS methylation
      defects typically with NESP hypermethylation versus XL and exon A/B
      hypomethylation while the imprinting of SNURF/SNRPN was normal. PHPIa patients
      showed an abnormal methylation in the three DMRs of GNAS. For the first time, a
      marked abnormal GNAS methylation was also found in 2 patients without PTH
      resistance but having hypocalcemia and hyperphosphatemia. CONCLUSIONS: The
      Sequenom EpiTYPER proves to be very sensitive in detecting DNA methylation
      changes. Our analysis also suggests that GNAS imprinting defects might be more
      frequent and diverse than previously thought.

PMID- 20807524
TI  - Effect of non-genetic factors on paraoxonase 1 activity in patients undergoing
      hemodialysis.
AB  - OBJECTIVES: Hemodialyzed patients have lower paraoxonase 1 (PON1) activity.
      Higher mortality risk from cardiovascular disease observed in these patients
      could be due to the low antiathetrogenic activity of PON1. Understanding the
      mechanism that causes lower PON1 activity could provide the possibility for
      modulation of enzyme activity in purpose of preventing and/or decreasing
      development of atherosclerosis. DESIGN AND METHODS: 87 healthy individuals and 71
      hemodialyzed patients were enrolled in this study. RESULTS: Hemodialyzed patients
      had reduced PON1 paraoxonase and arylesterase activity, concentrations of HDL,
      HDL(3) and HDL(2) and concentrations of free thiol groups. Distribution of HDL
      subfractions and distribution of PON1 phenotypes as well as concentrations of MDA
      were not different between two study groups. In the in vitro experiment high
      concentrations of urea, creatinine, uric acid and addition of patient's sera
      ultrafiltrate did not significantly affect PON1 paraoxonase activity. CONCLUSION:
      Decreased HDL concentration as well as lower PON1 concentration (shown indirectly
      by the enzyme arylesterase activity) might contribute, at least partly, to the
      reduced PON1 activity observed in hemodialyzed patients. Decreased concentration
      of free thiol groups in sera suggest that free thiol group (Cys284) in PON1 might
      also be oxidized, which can affect PON1 activity.

PMID- 20807525
TI  - Serum albumin and biomolecular oxidative damage of human atherosclerotic plaques.
AB  - OBJECTIVES: To investigate the association of serum albumin (SA) with oxidative
      damage of human atherosclerotic plaques and the severity of atherosclerosis.
      DESIGN AND METHODS: Correlation of the levels of SA with those of lipid and
      protein oxidation of endarterectomy-removed carotid atherosclerotic plaques; SA
      and plaque oxidative biomarkers comparison between 2 groups of patients with
      different severity of atherosclerotic carotid stenosis, i.e. <90% (group I) or
      >=90% (group II). RESULTS: SA was strongly inversely correlated with plaque
      oxidative damage; SA was lower and plaque oxidative damage higher in group II
      than group I. CONCLUSIONS: Lowered SA is associated with oxidative damage of
      atherosclerotic plaques and the severity of atherosclerosis.

PMID- 20807526
TI  - Epithelial: Endothelial cross-talk regulates exocrine differentiation in
      developing pancreas.
AB  - Endothelial cells are required to initiate pancreas development from the
      endoderm. They also control the function of endocrine islets after birth. Here we
      investigate in developing pancreas how the endothelial cells become organized
      during branching morphogenesis and how their development affects pancreatic cell
      differentiation. We show that endothelial cells closely surround the epithelial
      bud at the onset of pancreas morphogenesis. During branching morphogenesis, the
      endothelial cells become preferentially located near the central (trunk)
      epithelial cells and remain at a distance from the branch tips where acinar cells
      differentiate. This correlates with predominant expression of the angiogenic
      factor vascular endothelial growth factor-A (VEGF-A) in trunk cells. In vivo
      ablation of VEGF-A expression by pancreas-specific inactivation of floxed Vegfa
      alleles results in reduced endothelial development and in excessive acinar
      differentiation. On the contrary, acinar differentiation is repressed when
      endothelial cells are recruited around tip cells that overexpress VEGF-A.
      Treatment of embryonic day 12.5 explants with VEGF-A or with VEGF receptor
      antagonists confirms that acinar development is tightly controlled by endothelial
      cells. We also provide evidence that endothelial cells repress the expression of
      Ptf1a, a transcription factor essential for acinar differentiation, and stimulate
      the expression of Hey-1 and Hey-2, two repressors of Ptf1a activity. In explants,
      we provide evidence that VEGF-A signaling is required, but not sufficient, to
      induce endocrine differentiation. In conclusion, our data suggest that, in
      developing pancreas, epithelial production of VEGF-A determines the spatial
      organization of endothelial cells which, in turn, limit acinar differentiation of
      the epithelium.

PMID- 20807529
TI  - Open channel block of the fast transient outward K+ current by primaquine and
      chloroquine in rat left ventricular cardiomyocytes.
AB  - Anti-malarial drugs may have severe adverse cardiac effects as a result of their
      ion channel blocking properties. Here we investigate the effect of the
      aminoquinolines primaquine and chloroquine on the fast transient outward K(+)
      current (I(to)) of single epicardial myocytes isolated from the left ventricular
      free wall of female Wistar rats. The ruptured-patch whole-cell configuration of
      the patch-clamp technique was used to investigate I(to). At +60 mV, primaquine
      blocked I(to) amplitude (defined as the current inactivating during a test pulse
      of 600 ms duration) with an IC(50) of 118+/-8 MUM. I(to) charge was blocked with
      an IC(50) of 33+/-2 MUM (n=42), indicating open channel block. Chloroquine
      blocked I(to) amplitude with an IC(50) of 4.6+/-0.9 mM, while the IC(50) for
      I(to) charge was 439+/-63 MUM (n=23). The kinetic analysis of the onset of block
      revealed K(d) values of 52+/-8 MUM (n=18) and 520+/-60MUM (n=11) for primaquine
      and chloroquine, respectively. Both drugs significantly accelerated the apparent
      inactivation time constant of I(to). Steady-state inactivation of I(to) was not
      altered by 30 MUM primaquine. In contrast, I(to) recovery from inactivation was
      prolonged with the appearance of an additional long time constant without a
      change of the short time constant. Exposure to 1mM chloroquine resulted in a
      right shift of steady-state inactivation, whereas recovery from inactivation was
      only mildly affected. Both substances exhibited considerable use dependence. In
      X. laevis oocytes heterologously expressing hKv4.2+hKChIP2b channels the block by
      the aminoquinolines was voltage dependent. We conclude that primaquine and
      chloroquine are open-channel blockers of I(to).

PMID- 20807528
TI  - Crossveinless-2 is required for the relocalization of Chordin protein within the
      vertebral field in mouse embryos.
AB  - Bone morphogenetic proteins (BMPs), as well as the BMP-binding molecules Chordin
      (Chd), Crossveinless-2 (CV2) and Twisted Gastrulation (Tsg), are essential for
      axial skeletal development in the mouse embryo. We previously reported a strong
      genetic interaction between CV2 and Tsg and proposed a role for this interaction
      in the shaping of the BMP morphogenetic field during vertebral development. In
      the present study we investigated the roles of CV2 and Chd in the formation of
      the vertebral morphogenetic field. We performed immunostainings for CV2 and Chd
      protein on wild-type, CV2(-/-) or Chd(-/-) mouse embryo sections at the stage of
      onset of the vertebral phenotypes. By comparing mRNA and protein localizations we
      found that CV2 does not diffuse away from its place of synthesis, the vertebral
      body. The most interesting finding of this study was that Chd synthesized in the
      intervertebral disc accumulates in the vertebral body. This relocalization does
      not take place in CV2(-/-) mutants. Instead, Chd was found to accumulate at its
      site of synthesis in CV2(-/-) embryos. These results indicate a CV2-dependent
      flow of Chd protein from the intervertebral disc to the vertebral body. Smad1/5/8
      phosphorylation was decreased in CV2(-/-)vertebral bodies. This impaired BMP
      signaling may result from the decreased levels of Chd/BMP complexes diffusing
      from the intervertebral region. The data indicate a role for CV2 and Chd in the
      establishment of the vertebral morphogenetic field through the long-range
      relocalization of Chd/BMP complexes. The results may have general implications
      for the formation of embryonic organ-forming morphogenetic fields.

PMID- 20807530
TI  - Schistosoma mansoni: schistosomicidal effect of mefloquine and primaquine in
      vitro.
AB  - We investigated the effects of the anti-malarials mefloquine and primaquine
      against the juvenile and adult life stages of Schistosoma mansoniin vitro.
      Cercariae were incubated with 0.5 MUg/ml, 1 MUg/ml and 2 MUg/ml mefloquine or
      primaquine and with 1 MUg/ml praziquantel for 12h. Schistosomula, pre-adults and
      adults were incubated with 0.5 MUg/ml, 1 MUg/ml and 2 MUg/ml mefloquine or
      primaquine and with 1 MUg/ml praziquantel for 7 days. The viability status was
      classified as viable, damaged or dead and was checked every 3h for cercariae and
      every 12h for schistosomula, pre-adults and adults. Both, mefloquine and
      primaquine show time and dose-dependent schistosomicidal effects on the four life
      stages of S. mansoni. The promising in vitro effects on all stages of the blood
      fluke S. mansoni warrants further evaluation of both anti-malarials and their
      derivatives for their prophylactic and therapeutic values in early and late
      schistosomiasis in field trials.

PMID- 20807527
TI  - Endoderm development in Caenorhabditis elegans: the synergistic action of ELT-2
      and -7 mediates the specification->differentiation transition.
AB  - The transition from specification of cell identity to the differentiation of
      cells into an appropriate and enduring state is critical to the development of
      embryos. Transcriptional profiling in Caenorhabditis elegans has revealed a large
      number of genes that are expressed in the fully differentiated intestine;
      however, no regulatory factor has been found to be essential to initiate their
      expression once the endoderm has been specified. These gut-expressed genes
      possess a preponderance of GATA factor binding sites and one GATA factor, ELT-2,
      fulfills the expected characteristics of a key regulator of these genes based on
      its persistent expression exclusively in the developing and differentiated
      intestine and its ability to bind these regulatory sites. However, a striking
      characteristic of elt-2(0) knockout mutants is that while they die shortly after
      hatching owing to an obstructed gut passage, they nevertheless contain a gut that
      has undergone complete morphological differentiation. We have discovered a second
      gut-specific GATA factor, ELT-7, that profoundly synergizes with ELT-2 to create
      a transcriptional switch essential for gut cell differentiation. ELT-7 is first
      expressed in the early endoderm lineage and, when expressed ectopically, is
      sufficient to activate gut differentiation in nonendodermal progenitors. elt-7 is
      transcriptionally activated by the redundant endoderm-specifying factors END-1
      and -3, and its product in turn activates both its own expression and that of elt
      2, constituting an apparent positive feedback system. While elt-7 loss-of
      function mutants lack a discernible phenotype, simultaneous loss of both elt-7
      and elt-2 results in a striking all-or-none block to morphological
      differentiation of groups of gut cells with a region-specific bias, as well as
      reduced or abolished gut-specific expression of a number of terminal
      differentiation genes. ELT-2 and -7 synergize not only in activation of gene
      expression but also in repression of a gene that is normally expressed in the
      valve cells, which immediately flank the termini of the gut tube. Our results
      point to a developmental strategy whereby positive feedback and cross-regulatory
      interactions between two synergistically acting regulatory factors promote a
      decisive and persistent transition of specified endoderm progenitors into the
      program of intestinal differentiation.

PMID- 20807531
TI  - Detection of anti-oxidant enzymatic activities and purification of glutathione
      transferases from Angiostrongylus cantonensis.
AB  - There are several anti-oxidant enzyme families that play pivotal roles in
      facilitating the survival of parasites. Glutathione transferases (GSTs) are
      members of the anti-oxidant family that can detoxify a broad range of exogenous
      or endogenous compounds including reactive oxidative species. GSTs have been
      studied as vaccine candidates, immunodiagnostic markers and as treatment targets.
      Helminths of the genus Angiostrongylus live inside arteries of vertebrates and
      two main species are associated with accidental human infections: Angiostrongylus
      costaricensis adult worms live inside the mesenteric arteries and larvae of
      Angiostrongylus cantonensis become trapped in the central nervous system
      vasculature. Since the interactions between angiostrongylid nematodes and their
      vertebrate hosts are poorly understood, this study characterized the anti-oxidant
      enzymatic activities of A. cantonensis from female worms by collecting excreted
      and secreted (ES) and total extract (TE) molecules. Catalase (CAT) and superoxide
      dismutase (SOD) activities were found both in the ES and TE while glutathione
      peroxidase (GPX) and GST were found only in the TE. GSTs were purified by
      glutathione agarose affinity column (AcGST) and the pool of eluted GSTs was
      analyzed by mass spectrometry (LC-MS/MS) and de novo sequencing (Masslynx
      software). Sequences from two peptides (AcGSTpep1 and AcGSTpep2) present high
      identity to the N-terminal and C-terminal from sigma class GSTs of nematodes. It
      is known that these GST enzymes are associated with host immune regulation.
      Furthermore, understanding the role of parasite-derived anti-oxidant molecules is
      important in understanding host-parasite interactions.

PMID- 20807532
TI  - Development of a cell-free system reveals an oxygen-labile step in the maturation
      of [NiFe]-hydrogenase 2 of Escherichia coli.
AB  - By combining extracts from strains lacking genes encoding either the maturation
      enzymes or the large subunits of hydrogenases 1, 2 and 3 we could reconstitute in
      vitro under strictly anaerobic conditions 10-15% of the hydrogenase activity
      present in wild type Escherichia coli extracts. Purified, unprocessed Strep
      tagged variants of the hydrogenase 2 large subunit, HybC, isolated from either a
      DeltahybD (encoding the hydrogenase 2-specific protease) mutant or a strain
      deficient in HypF could also be matured to active, processed enzyme using this
      system. These studies reveal that minimally one step early on the hydrogenase
      maturation pathway is oxygen-labile.

PMID- 20807533
TI  - Binding and catalysis of Humulus lupulus adenylate isopentenyltransferase for the
      synthesis of isopentenylated diadenosine polyphosphates.
AB  - Various plant developmental processes involve phytohormones such as cytokinins.
      Isopentenyltransferase (IPT) reaction is the key rate-limiting step in cytokinin
      biosynthesis that transfers the isopentenyl (iP) group from dimethylallyl
      diphosphate to the N6-amino group of adenine. Here, a series of diadenosine
      polyphosphates (Ap(n)A) were screened as possible substrates of IPT, among which
      diadenosine tetraphosphate, diadenosine pentaphosphate and diadenosine
      hexaphosphate showed higher affinity than did the authentic substrates ADP and
      ATP. In addition, formation of mono-isopentenyl Ap(n)A and di-isopentenyl Ap(n)A
      was observed. Judging by the existing biosynthetic and hydrolytic systems for
      Ap(n)A in plants, Ap(n)A and isopentenyl-Ap(n)A may occur in the plant cells,
      with functional importance.

PMID- 20807534
TI  - Activation of ERalpha is necessary for estradiol's anorexigenic effect in female
      rats.
AB  - While there is considerable evidence that the ovarian hormone estradiol reduces
      food intake in female rats, it is unclear which estrogen receptor (ER) subtype,
      ERalpha or ERbeta, mediates this effect. While several studies have demonstrated
      that activation of ERalpha, but not ERbeta, is sufficient to reduce food intake
      in ovariectomized (OVX) rats, there are limited data regarding which receptor
      subtype is necessary. Here we used the selective ERalpha and ERbeta antagonists,
      MPrP and PHTPP, respectively, to investigate this question. We found that
      antagonism of ERalpha, but not ERbeta, prevented the decrease in food intake
      following acute administration of estradiol in OVX rats. In addition, antagonism
      of ERalpha prevented the estrous-related, phasic reduction in food intake that
      occurs in response to the rise in circulating levels of estradiol in cycling
      rats. We conclude that activation of ERalpha is necessary for the anorexigenic
      effects of exogenous and endogenous estradiol in female rats.

PMID- 20807535
TI  - Selection for fast and slow exploration affects baseline and stress-induced
      corticosterone excretion in Great tit nestlings, Parus major.
AB  - In nestlings, glucocorticoid (GC) secretion has short-term and long-term fitness
      consequences. For example, short-time elevations trigger begging activity,
      whereas chronically elevated GC levels impair body condition, growth and
      cognitive abilities. Despite a growing body of literature on personality traits,
      the effects of selection for fast and slow exploration on GC secretion have
      received little attention. We compared baseline and stress-induced hypothalamic
      pituitary-adrenal (HPA) axis activity of hand-reared great tit nestlings of lines
      selected for fast and slow exploration. Nestling droppings were collected under
      three conditions: control, test (following handling stress, day 14 after
      hatching) and the following day. The concentrations of excreted immunoreactive
      corticosterone metabolites (CM) were determined via an enzyme immunoassay. We
      also observed nestlings' begging behaviour. CM differed significantly between the
      lines. Nestlings of the fast line excreted lower CM than slow-line birds. In
      response to handling stress, nestlings excreted significantly higher
      concentrations of CM than during the control and on the day after handling. Sex
      and begging activity were not related to CM levels. Under the control condition,
      but not after handling, males begged significantly more often than females. In
      both lines, adults excreted significantly less CM compared to nestlings. Both
      nestlings and adults of the slow line produced higher baseline CM values than
      fast-line birds. Fast-line nestlings excreted lower baseline CM than nestlings of
      a wild population not selected for fast or slow exploration. Slow-line nestlings
      did not. Our results show that selection on the basis of exploratory behaviour
      affected HPA axis reactivity.

PMID- 20807536
TI  - Evidence for a novel Entamoeba histolytica lectin activity that recognises
      carbohydrates present on ovalbumin.
AB  - Entamoeba histolytica, an intestinal amoeba that causes dysentery and liver
      abscesses, acquires nutrients by engulfing bacteria in the colonic lumen and
      phagocytoses apoptotic cells during tissue invasion. In preliminary studies to
      identify ligands that stimulate amoebic phagocytosis, we used ovalbumin
      immobilized on latex particles as a potential negative control protein.
      Surprisingly, ovalbumin strongly stimulated E. histolytica particle uptake.
      Experiments using highly purified ovalbumin confirmed the specificity of this
      finding. The mechanism of particle uptake was actin-dependent, and the Entamoeba
      phagosome marker amoebapore A localised to ovalbumin-bead containing vacuoles.
      The most well described amoebic receptor is a Gal/GalNAc-specific lectin, but d
      galactose had no effect on ovalbumin-stimulated phagocytosis. Ovalbumin has a
      single N-glycosylation site (Asn(292)) and is modified with oligomannose and
      hybrid-type oligosaccharides. We used both trifluoromethanesulfonic acid and N
      glycanase to deglycosylate ovalbumin and tested the effect. Both methods
      substantially reduced the stimulatory effect of ovalbumin. Biotinylated ovalbumin
      bound the surface of fixed E. histolytica trophozoites saturably; furthermore,
      denatured ovalbumin and native ovalbumin both specifically inhibited ovalbumin
      biotin binding, but deglycosylated ovalbumin had no effect. Collectively, these
      data suggest that E. histolytica has a previously unrecognised surface lectin
      activity that binds to carbohydrates on ovalbumin and stimulates phagocytosis.

PMID- 20807537
TI  - Primary hemocyte culture of Penaeus monodon as an in vitro model for white spot
      syndrome virus titration, viral and immune related gene expression and
      cytotoxicity assays.
AB  - Immortal cell lines have not yet been reported from Penaeus monodon, which
      delimits the prospects of investigating the associated viral pathogens especially
      white spot syndrome virus (WSSV). In this context, a method of developing primary
      hemocyte culture from this crustacean has been standardized by employing modified
      double strength Leibovitz-15 (L-15) growth medium supplemented with 2% glucose,
      MEM vitamins (1*), tryptose phosphate broth (2.95 gl-1), 20% FBS, N
      phenylthiourea (0.2 mM), 0.06 MUg ml-1 chloramphenicol, 100 MUg ml-1 streptomycin
      and 100 IU ml-1 penicillin and hemolymph drawn from shrimp grown under a bio
      secured recirculating aquaculture system (RAS). In this medium the hemocytes
      remained viable up to 8 days. 5-Bromo-2'-deoxyuridine (BrdU) labeling assay
      revealed its incorporation in 22 +/- 7% of cells at 24h. Susceptibility of the
      cells to WSSV was confirmed by immunofluorescence assay using a monoclonal
      antibody against 28 kDa envelope protein of WSSV. A convenient method for
      determining virus titer as MTT(50)/ml was standardized employing the primary
      hemocyte culture. Expression of viral genes and cellular immune genes were also
      investigated. The cell culture could be demonstrated for determining toxicity of
      a management chemical (benzalkonium chloride) by determining its IC(50). The
      primary hemocyte culture could serve as a model for WSSV titration and viral and
      cellular immune related gene expression and also for investigations on
      cytotoxicity of aquaculture drugs and chemicals.

PMID- 20807538
TI  - Experimental evaluation of the pathogenicity of Perkinsus olseni in juvenile
      Manila clams Ruditapes philippinarum.
AB  - We evaluated the pathogenicity of Perkinsus olseni towards the Manila clam,
      Ruditapes philippinarum, by an experimental challenge. For production of
      prezoosporangia of P. olseni, we injected uninfected Manila clams with cells of a
      pure strain of P. olseni and reared them for 7d. Prezoosporangia were isolated
      from the soft tissue of the injected clams after culturing in Ray's fluid
      thioglycollate medium. Hatchery-reared, uninfected juvenile clams (3-10 mm shell
      length) were challenged by immersion in one of two concentrations of a
      prezoosporangial suspension of P. olseni for 6d. The challenged clams had
      significantly higher mortality at both the concentrations than the unchallenged
      clams. The mortality due to infection dose-dependently began approximately 4
      weeks and 7 weeks after challenge in the higher and lower concentrations,
      respectively. This is the first experimental evidence that P. olseni causes
      direct mortality in Manila clams. The lethal level of infection was estimated at
      approximately 107 pathogen cells/g soft tissue weight.

PMID- 20807539
TI  - Costs and benefits of Wolbachia infection in immature Aedes albopictus depend
      upon sex and competition level.
AB  - Bacterial endosymbionts induce various effects on hosts and can dramatically
      impact host fitness and development. An example is provided by obligate,
      maternally-inherited Wolbachia, which infect a broad range of invertebrates.
      Wolbachia are capable of altering host reproduction, thereby promoting infection
      spread. Wolbachia also pose direct physiological costs and benefits to hosts,
      complicating their categorization as parasites or mutualists. This study examines
      for an effect of Wolbachia infection in intra-specific larval competition by
      Aedes albopictus mosquitoes, with the goal of examining for an impact of
      Wolbachia infection in mixed populations. Similar to prior work examining for an
      influence of Wolbachia infection on the fitness of A. albopictus in adults, the
      results presented here support the hypothesized impact of Wolbachia across all
      life stages, including immatures. The differential competitiveness of infected
      larvae detected in our experiments indicates that Wolbachia infected A.
      albopictus females are less competitive relative to uninfected females when
      competing under highly competitive conditions. In contrast, under low competitive
      pressures, infected females experience higher survivorship. Thus, Wolbachia
      infection shifts from parasitism to mutualism as a function of developmental
      conditions. Results are discussed in relation to the invasion and persistence of
      Wolbachia in A. albopictus populations. The results are important to the
      evolution of stable Wolbachia symbioses, including Wolbachia invasion of an
      uninfected population. The resulting infection dynamics that occur in an infected
      population are discussed.

PMID- 20807540
TI  - Effects of culture media on hydrophobicity and thermotolerance of Bb and Ma
      conidia, with description of a novel surfactant based hydrophobicity assay.
AB  - Hypocrealean entomopathogenic fungal conidia are made up of multi-aged groups
      given their chronological conidiogenesis. Most thermotolerance assays have been
      conducted using mixed-age conidia. The present work exploited a polysiloxane
      polyether copolymer (siloxane) (Silwet L-77(r)) mediated conidial collection
      method, validated by a hydrophobicity assay. This was done to divide mixed-age
      conidia into two groups based on hydrophobicity and test their thermotolerance,
      relying on the relationship of conidial age with hydrophobicity. Beauveria
      bassiana GHA and ERL1170 and Metarhizium anisopliae ERL1171 and ERL1540 conidia,
      produced on millet agar, whey permeate agar, and 1/4SDAY were subjected to
      hydrophobicity assays that included data on yield of conidia/unit of surface
      area. Conidia were also collected using 0.01% siloxane, and those remaining with
      0.08% siloxane. Hydrophobicity was correlated with percent conidia collected in
      the two siloxane solutions and yield, suggesting a relationship between percent
      conidia collected and conidial age (maturation). The conidial suspensions were
      exposed to 45 degrees C for 45min, and conidial germination was examined.
      Overall, conidia which were collected in 0.08% siloxane had lower germination
      after heat exposure than those collected in the 0.01% solution. Conidia of both
      fungi produced by incubation on millet or whey permeate for 14d were more
      hydrophobic and exhibited greater thermotolerance than those produced on 1/4SDAY.
      These results suggest that conidia can be divided into two groups with different
      thermotolerance by using a siloxane-mediated conidial collection method based on
      hydrophobicity. This depends on the types of substrates used that could influence
      conidial maturation.

PMID- 20807541
TI  - Interactions between imidacloprid and Metarhizium brunneum on adult Asian
      longhorned beetles (Anoplophora glabripennis (Motschulsky)) (Coleoptera:
      Cerambycidae).
AB  - Anoplophora glabripennis (Motschulsky) (Coleoptera: Cerambycidae), a longhorned
      beetle species native to Asia, has been introduced into several North American
      and European cities. Currently eradication and preventive measures are limited to
      identifying and destroying infested trees and protecting uninfested trees with
      trunk or soil-injections of the systemic insecticide imidacloprid. Because
      entomopathogenic fungi like Metarhizium brunneum Petch have been identified as
      virulent against these beetles we conducted several tests to determine the
      compatibility of the two agents in combination. Radial hyphal growth and the
      sporulation capacity of M. brunneum on Sabouraud dextrose agar with yeast were
      not significantly affected by the presence of imidacloprid. In a 2*3 factorial
      experiment investigating interactions between exposure to imidacloprid and M.
      brunneum we observed no effect of imidacloprid alone on beetle survival when
      beetles were given a single dose of 10 or 100 ppm compared to control insects. We
      observed a significant effect of exposure to M. brunneum, and a significant
      interaction between imidacloprid and M. brunneum representing a synergistic
      effect of dual treatment. Beetles exposed to the fungus alone lived significantly
      longer compared to insects treated with a single dose of 100 ppm imidacloprid
      (9.5 vs. 6.5d). Consumption of striped maple twigs by beetles exposed to
      imidacloprid, across concentrations, was reduced 48% compared to control insects,
      where as consumption by M. brunneum-exposed beetles was reduced by 16% over the
      first 6-days of the test period. Beetles fed 100 ppm imidacloprid consumed 32%
      less over the first 3d compared to beetles not exposed to imidacloprid and
      thereafter consumed as much as beetles not fed 100 ppm imidacloprid. M. brunneum
      exposed beetles consumed significantly less food than control insects throughout
      the test period, and beetles treated with imidacloprid produced significantly
      fewer conidia compared to beetles not treated with imidacloprid.

PMID- 20807543
TI  - Critical role for white blood cell NAD(P)H oxidase-mediated plasminogen activator
      inhibitor-1 oxidation and ventricular rupture following acute myocardial
      infarction.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is an oxidant-sensitive protease
      inhibitor that is inactivated by oxidation and has a critical role in ventricular
      remodeling post myocardial infarction (MI). PAI-1 knockout (KO) mice die within
      7days of myocardial infarction post MI due to increased plasmin activity leading
      to ventricular rupture. The goal of this study was to assess the relevant
      pathways of leukocyte-derived oxidants post MI that alter PAI-1 activity.
      Transplantation of wild-type (WT) bone marrow into PAI-1 null mice prolonged
      survival after MI (WT marrow: 41.66% vs. PAI-1 KO marrow: 0% in PAI-1 KO mice at
      day 7 (p<0.02). To determine relevant enzyme systems, we transplanted marrow from
      mice with specific deletions relevant to leukocyte-derived oxidants (NAD(P)H
      oxidase, iNOS, myeloperoxidase (MPO)) to determine which deletion controls PAI-1
      oxidative inactivation and prolongs survival. MI was induced by ligation of the
      left anterior descending artery (LAD) and the incidence of cardiac rupture was
      monitored. PAI-1 KO transplanted with MPO KO, or iNOS KO bone marrow died within
      9 days after MI. PAI-1 KO mice transplanted with p47(phox) KO marrow exhibited
      prolonged survival 21 days after MI (30% survival, p<0.03, n=10) compared to WT
      marrow (8.3%, n=12). Three days after MI, PAI-1 KO mice transplanted with
      p47(phox) KO marrow had increased PAI-1 activity and decreased nitration of PAI-1
      in myocardial tissue compared to PAI-1 KO mice transplanted with WT marrow. These
      data suggest that modulating O(2)(*-) generation by NAD(P)H oxidase appears to be
      a therapeutically relevant target for increasing myocardial PAI-1 levels after
      MI, whereas downstream enzymes like MPO and iNOS may not be.

PMID- 20807542
TI  - Histidine-rich calcium binding protein: the new regulator of sarcoplasmic
      reticulum calcium cycling.
AB  - The histidine-rich calcium binding protein (HRC) is a novel regulator of
      sarcoplasmic reticulum (SR) Ca(2+)-uptake, storage and release. Residing in the
      SR lumen, HRC binds Ca(2+) with high capacity but low affinity. In vitro
      phosphorylation of HRC affects ryanodine affinity of the ryanodine receptor
      (RyR), suggesting a functional role of HRC on SR Ca(2+)-release. Indeed, acute
      HRC overexpression in isolated rodent cardiomyocytes decreases Ca(2+)-induced
      Ca(2+)-release, increases SR Ca(2+)-load, and impairs contractility. The HRC
      effects on RyR may be regulated by the Ca(2+)-sensitivity of its interaction with
      triadin. However, HRC also affects the SR Ca(2+)-ATPase, as shown by HRC
      overexpression in transgenic mouse hearts, which resulted in reduced SR Ca(2+)
      uptake rates, cardiac remodeling and hypertrophy. In fact, in vitro generated
      evidence suggests that HRC directly interacts with SR Ca(2+)-ATPase2, supporting
      a dual role of HRC in Ca(2+)-homeostasis: regulation of both SR Ca(2+)-uptake and
      Ca(2+)-release. Furthermore, HRC plays an important role in myocyte
      differentiation and in antiapoptotic cardioprotection against
      ischemia/reperfusion induced cardiac injury. Interestingly, HRC has been linked
      with familiar cardiac conduction disease and an HRC polymorphism was shown to
      associate with malignant ventricular arrhythmias in the background of idiopathic
      dilated cardiomyopathy. This review summarizes studies, which have established
      the critical role of HRC in Ca(2+)-homeostasis, suggesting its importance in
      cardiac physiology and pathophysiology.

PMID- 20807544
TI  - Partial rescue of the Tbx1 mutant heart phenotype by Fgf8: genetic evidence of
      impaired tissue response to Fgf8.
AB  - Tbx1 is the candidate gene of DiGeorge syndrome and is required in humans and
      mice for the development of the cardiac outflow tract (OFT) and aortic arch
      arteries. Loss of function mutants present with reduced cell proliferation and
      premature differentiation of cardiac progenitor cells of the second heart field
      (SHF). Tbx1 regulates Fgf8 expression hence the hypothesis that the proliferation
      impairment may contribute to the heart phenotype of mutants. Here we show that
      forced Fgf8 expression modifies and partially rescues the OFT septation defects
      of Tbx1 mutants but only if there is some residual expression of Tbx1. This
      genetic experiment suggests that Tbx1, directly or indirectly, affects tissue
      response to Fgf8. Indeed, Tbx1(-/-) mouse embryonic fibroblasts were unable to
      respond to Fgf8 added to the culture media and showed defective response of
      Erk1/2 and Rsk1. Our data suggest a coordinated pathway modulating Fgf8 ligand
      expression and tissue response to it in the SHF.

PMID- 20807545
TI  - Bisphenol A induces endoplasmic reticulum stress-associated apoptosis in mouse
      non-parenchymal hepatocytes.
AB  - AIMS: the effects of bisphenol A (BPA) on NCTC Clone 1469, non-parenchymal
      hepatocytes, were examined to clarify the molecular basis of BPA-induced liver
      injury. MAIN METHODS: we analyzed the expression of C/EBP homologous protein
      (CHOP) mRNA, Bcl2 mRNA, caspase12, and glucose-regulated protein 78 kDa
      (GRP78)/Ig heavy chain-binding protein (BiP), to determine whether endoplasmic
      reticulum (ER) stress was involved in the 100 MUM BPA-induced cell death. To
      examine the features of damaged hepatocytes, we analyzed the morphological
      changes in BPA-treated NCTC Clone 1469 by transmission electron microscopy. In
      addition, we analyzed the intracellular reactive oxygen species (ROS) level in
      BPA-treated NCTC Clone 1469 by the 2', 7'-dichlorofluorescein diacetate (DCFDA)
      method. KEY FINDINGS: increases in the expression of CHOP mRNA, caspase-12, and
      GRP78/BiP in NCTC Clone 1469-treated with 100 MUM BPA were detected (CHOP, 1.42
      fold; caspase-12, 1.33 fold; GRP78/Bip, 1.36 fold). These observations suggested
      that BPA induced ER stress-associated apoptosis. A morphological analysis
      revealed remarkable elongation of the rough ER, supporting the finding of ER
      stress. Intracellular ROS production was increased in NCTC Clone 1469-treated
      with BPA, and N-acetyl-l-cysteine (NAC) prevented the cell damage induced by BPA.
      However, these effects of BPA were not inhibited by estrogen receptor inhibitors.
      SIGNIFICANCE: we found that BPA induced ER stress-associated apoptosis in non
      parenchymal hepatocytes. The ER stress is due to ROS production and is
      independent of estrogen receptors.

PMID- 20807546
TI  - Carbon monoxide derived from heme oxygenase-2 mediates reduction of methylmercury
      toxicity in SH-SY5Y cells.
AB  - We examined the contribution of carbon monoxide (CO), an enzymatic product of
      heme oxygenase (HO), to methylmercury (MeHg) cytotoxicity in SH-SY5Y cells,
      because this gas molecule is reported to activate Nrf2, which plays a protective
      role against MeHg-mediated cell damage. Exposure of SH-SY5Y cells to CO gas
      resulted in protection against MeHg cytotoxicity, with activation of Nrf2.
      Interestingly, pretreatment with tin-protoporphyrin IX, a specific inhibitor of
      HO, caused a reduction in basal Nrf2 activity and thus enhanced sensitivity to
      MeHg. No induction of isoform 1 of HO (HO-1) was seen during MeHg exposure, but
      constitutive expression of isoform 2 (HO-2) occurred, suggesting that CO produced
      by HO-2 is the main participant in the protection against MeHg toxicity. Studies
      of small interfering RNA-mediated knockdown of HO-2 in the cells supported this
      possibility. Our results suggest that CO gas and its producing enzyme HO-2 are
      key molecules in cellular protection against MeHg, presumably through basal
      activation of Nrf2.

PMID- 20807548
TI  - Single and repeated baclofen treatment attenuates the discriminative stimulus
      effects of morphine in rats.
AB  - The GABA(B) agonists block the rewarding properties of opiates. However, the role
      of GABA(B) receptors in the discriminative properties of these drugs has received
      little attention. In this line, the present study was performed to investigate
      the effects of acute (Experiment 1) and chronic (Experiment 2) pretreatment with
      baclofen on the discriminative stimulus effects of morphine. Rats were trained to
      discriminate morphine (5mg/kgi.p.) from saline under a two-lever fixed-ratio
      schedule of food reinforcement. Experiment 1: a morphine generalization curve was
      obtained under standard conditions in control and baclofen (1 and 2mg/kgi.p.)
      pretreated animals. Acute baclofen pretreatment attenuated morphine-lever
      responding and response rate at both doses. Experiment 2: the animals were
      randomly divided in two groups and a morphine generalization curve was obtained
      in daily consecutive test sessions before (TEST1) and after (TEST2) chronic
      saline (Group I) or chronic baclofen (2mg/kg) (Group II) administration. As
      expected, chronic saline pretreatment was ineffective, while chronic baclofen
      pretreatment attenuated the stimulus properties of morphine, without modifying
      the rate-decreasing effect of the drug.The data support a role for GABAergic
      neurotransmission in the discriminative effects of opiates and demonstrate that a
      short-term treatment with baclofen is useful for decreasing the sensitivity to
      narcotic cue.

PMID- 20807547
TI  - No capture outside the attentional window.
AB  - A recent study has proposed that attentional window determines when the color
      singletons capture visual attention (Belopolsky, Zwaan, Theeuwes, & Kramer,
      2007). The present study used the additional singleton paradigm of Theeuwes
      (1992) and showed that capture was abolished when the size of the attentional
      window was reduced by focusing on RSVP stream in the center of the screen.
      Narrowing of attentional window also resulted in increase in search slope even in
      such a simple task as the pop-out detection. These findings suggest that
      attentional window plays a crucial role in visual selection and in the occurrence
      of attentional capture.

PMID- 20807549
TI  - Differential regulation of female sexual behaviour by dopamine agonists in the
      medial preoptic area.
AB  - The medial preoptic area (mPOA) is a brain region critical in the control of male
      sexual behaviour, and the neurotransmitter dopamine (DA) plays an important role
      within it. However, both the roles of DA and the mPOA in female sexual behaviour
      are not fully understood, with few studies producing consistent data. The present
      study examined the function of DA within the mPOA on the full cascade of female
      sexual behaviour. Ovariectomized female rats were bilaterally cannulated into the
      mPOA and partially hormonally primed with estradiol benzoate (EB). Different
      doses of a nonselective DA receptor agonist, and selective DA D1 and D2 receptor
      agonists (apomorphine, SKF 38393 and quinpirole, respectively) were infused
      bilaterally to the mPOA. Copulatory behaviour was then immediately tested over a
      period of 30 min in a bilevel chamber with a sexually experienced male.
      Precopulatory behaviours were increased in females following infusions of a low
      dose (0.25MUg) of apomorphine and both a low (0.05MUg) and a high dose (0.2MUg)
      of quinpirole. However, hops and/or darts were decreased following infusion of a
      low dose (0.05MUg) of SKF 38393. These results suggest that the ratio of DA D1/D2
      activity within the mPOA of female rats is critical for the expression of
      precopulatory behaviours, and may work with other brain areas responsible for
      stimulating lordosis to control the timing of female sexual behaviour.

PMID- 20807550
TI  - High-throughput recombinant gene expression systems in Pichia pastoris using
      newly developed plasmid vectors.
AB  - We describe here the construction of Gateway-compatible vectors, pBGP1-DEST and
      pPICZalpha-DEST, for rapid and convenient preparation of expression plasmids for
      production of secretory proteins in Pichia pastoris. Both vectors direct the
      synthesis of fusion proteins consisting of the N-terminal signal and pro
      sequences of Saccharomyces cerevisiae alpha-factor, the recognition sites for
      Kex2 and Ste13 processing proteases, the mature region of a foreign protein
      flanked by attB1- and attB2-derived sequences at N- and C-termini, respectively,
      and myc plus hexahistidine tags added at the extreme C-terminus. To test the
      usefulness of these vectors, production of endo-glucanases and xylanases from
      termite symbionts, as well as a fungal glucuronoyl esterase, was performed.
      Enzyme activities were detected in the culture supernatants, indicating that the
      chimeric proteins were synthesized and secreted as designed.

PMID- 20807551
TI  - Acid-sensing ion channels (ASICs): pharmacology and implication in pain.
AB  - Tissue acidosis is a common feature of many painful conditions. Protons are
      indeed among the first factors released by injured tissues, inducing a local pH
      fall that depolarizes peripheral free terminals of nociceptors and leads to pain.
      ASICs are excitatory cation channels directly gated by extracellular protons that
      are expressed in the nervous system. In sensory neurons, they act as "chemo
      electrical" transducers and are involved in somatic and visceral nociception. Two
      highly specific inhibitory peptides isolated from animal venoms have considerably
      helped in the understanding of the physiological roles of these channels in pain.
      At the peripheral level, ASIC3 is important for inflammatory pain. Its expression
      and its activity are potentiated by several pain mediators present in the
      "inflammatory soup" that sensitize nociceptors. ASICs have also been involved in
      some aspects of mechanosensation and mechanonociception, notably in the
      gastrointestinal tract, but the underlying mechanisms remain to be determined. At
      the central level, ASIC1a is largely expressed in spinal cord neurons where it
      has been proposed to participate in the processing of noxious stimuli and in
      central sensitization. Blocking ASIC1a in the spinal cord also produces a potent
      analgesia in a broad range of pain conditions through activation of the opiate
      system. Targeting ASIC channels at different levels of the nervous system could
      therefore be an interesting strategy for the relief of pain.

PMID- 20807552
TI  - An evaluation of hERG current assay performance: Translating preclinical safety
      studies to clinical QT prolongation.
AB  - Block of delayed rectifier current (I(Kr), Kv11.1 encoding the hERG gene) is
      associated with delayed cardiac repolarization (QTc prolongation), a surrogate
      marker of proarrhythmia. Despite its recognized role in assessing QTc
      prolongation risk, a quantitative analysis of the utility and limitations of the
      hERG current assay has not been reported. To benchmark hERG assay performance,
      this retrospective study compared hERG block potency with drug-induced QTc
      prolongation assessed during rigorous thorough QT (TQT) clinical studies for 39
      drugs from multiple classes. To place block in context, hERG safety margins
      (IC(50) values for block/mean maximal plasma drug concentrations during TQT
      studies) were compared to QTc prolongation (QTc increase>=5ms). Most (9/10) drugs
      eliciting essentially no hERG block at maximal concentrations demonstrate no QTc
      prolongation despite representing a wide hERG safety margin range. Based on
      receiver-operator characteristics, a hERG safety margin of 45 provided optimal
      overall performance linking safety margins to QTc prolongation (sensitivity (true
      positive rate)=0.64, specificity (true negative rate)=0.88); the area under the
      receiver-operator curve (0.72) is indicative of moderate overall concordance.
      Likelihood ratios calculated from multitier contingency tables suggest that QTc
      prolonging drugs are only 5-7 times as likely to demonstrate low safety margins
      (1-30 range) compared to drugs that do not prolong QTc. Paradoxically, higher
      safety margins demonstrate lesser confidence predicting prolongation. The overall
      limitations of hERG safety margins shown using these quantitative, evidence-based
      approaches highlight the need for additional preclinical assays and adaptive
      strategies throughout drug discovery to reliably mitigate QTc prolongation risk.

PMID- 20807553
TI  - Mitochondrial localization of viral proteins as a means to subvert host defense.
AB  - Viruses have developed a battery of distinct strategies to overcome the very
      sophisticated defense mechanisms of the infected host. Throughout the process of
      pathogen-host co-evolution, viruses have therefore acquired the capability to
      prevent host cell apoptosis because elimination of infected cells via apoptosis
      is one of the most ancestral defense mechanism against infection. Conversely,
      induction of apoptosis may favor viral dissemination as a result of the
      dismantlement of the infected cells. Mitochondria have been long recognized for
      their key role in the modulation of apoptosis but more recently, mitochondria
      have been shown to serve as a crucial platform for innate immune signaling as
      illustrated by the identification of MAVS. Thus, it is therefore not surprising
      that this organelle represents a recurrent target for viruses, aiming to
      manipulate the fate of the infected host cell or to inhibit innate immune
      response. In this review, we highlight the viral proteins that are specifically
      targeted to the mitochondria to subvert host defense. This article is part of a
      Special Issue entitled Mitochondria: the deadly organelle.

PMID- 20807554
TI  - Detection of metallo-beta-lactamase genes in clinical specimens by a commercial
      multiplex PCR system.
AB  - hyplex(r)-MBL ID Multiplex PCR-ELISA, a novel method for identifying metallo-beta
      lactamase genes directly in clinical specimens, was evaluated using a consecutive
      collection of 326 samples from three hospitals in Greece characterized by high
      prevalence of VIM producers. The method exhibited high sensitivity (98.0%) and
      specificity (98.6%) and was proven reliable in detecting bla(VIM) genes in blood,
      urine, pus, and sputum samples that, as confirmed by conventional methods,
      contained various VIM-producing species. Future multicenter studies should be
      considered for the thorough evaluation of this method and its potential
      diagnostic utility.

PMID- 20807555
TI  - Sensitive immunoassay of Listeria monocytogenes with highly fluorescent
      bioconjugated silica nanoparticles probe.
AB  - In this paper, a sensitive immunoassay method was proposed for Listeria
      monocytogenes detection by using highly fluorescent bioconjugated nanoparticles
      probe. (FITC-IgG)-doped fluorescent silica nanoparticles (fsNPs) firstly were
      synthesized by a microemulsion method and characterized by TEM and fluorescent
      spectra. Then the prepared fsNPs were conjugated with polyclonal rabbit anti-L.
      monocytogenes antibody (pAb) and used as indicator probe. A sandwich-type immune
      affinity reaction between polyclonal rabbit anti-L. monocytogenes antibody coated
      onto microplate wells, target bacteria and the fsNPs-antibody conjugates
      subsequently was conducted to detect target L. monocytogenes and assemble the
      indicator probe onto the wells. The target L. monocytogenes was measured by the
      fluorescent signals of the assembled indicator probes. Under the optimal
      conditions, the calibration graph of fluorescent intensity is proportional to the
      amount of target bacteria over the range of 50-10,320 CFU/mL with a detection
      limit of 50 CFU/mL. The proposed method has been successfully applied to detect
      L. monocytogenes in food samples offering the advantages of sensitivity,
      simplicity, and stability.

PMID- 20807556
TI  - New method for electroporation of Lactobacillus species grown in high salt.
AB  - We here describe a new method for electroporation of Lactobacillus species,
      obligately homofermentative and facultatively heterofermentative, based on the
      cell-wall weakening resulting from growth in high-salt media. For L. casei,
      optimum transformation efficiency of up to 10(5) transformants per microgram of
      plasmid DNA was achieved following growth in the presence of 0.9 M NaCl. Plasmids
      of different sizes and replication origins were also similarly transformed. These
      competent cells could be used either directly or stored frozen, up to 1 month,
      for future use, with similar efficiency. This protocol was assayed with different
      Lactobacillus species: L. delbrueckii subsp. lactis, L. paracasei, L. plantarum
      and L. acidophilus, and it was found that they were transformed with similar
      efficiency.

PMID- 20807557
TI  - Fluorescence in situ hybridization rapidly detects three different pathogenic
      bacteria in urinary tract infection samples.
AB  - The detection of pathogenic bacteria in urine is an important criterion for
      diagnosing urinary tract infections (UTIs). By using fluorescence in situ
      hybridization (FISH) with rRNA-targeted, fluorescently labeled oligonucleotide
      probes, bacterial pathogens present in urine samples were identified within 3-4
      h. In this study, three probes that are specific for Escherichia coli,
      Enterococcus faecalis and Staphylococcus aureus were designed based on the
      conserved 16S RNA sequences, whereas probe Eub338 broadly recognizes all
      bacteria. We collected a total of 1000 urine samples, and 325 of these samples
      tested positive for a UTI via traditional culturing techniques; additionally, all
      325 of these samples tested positive with the Eub338 probe in FISH analysis. FISH
      analyses with species-specific probes were performed in parallel to the test the
      ability to differentiate among several pathogenic bacteria. The samples for these
      experiments included 76 E. coli infected samples, 32 E. faecalis infected samples
      and 9 S. aureus infected samples. Compared to conventional methods of bacterial
      identification, the FISH method produced positive results for >90% of the samples
      tested. FISH has the potential to become an extremely useful diagnostic tool for
      UTIs because it has a quick turnaround time and high accuracy.

PMID- 20807558
TI  - Limitations in the characterisation of cigarette products using different machine
      smoking regimes.
AB  - It is recognised that no single machine smoking regime can represent the
      different behaviours of individual human smokers. It has been argued that the
      current ISO standard regime provides machine yields that are somewhat low for
      certain cigarette designs compared to human intake. Various cigarette machine
      smoking regimes have been proposed as options for regulatory use to provide data
      that reflect "average" or "maximum" yields as related to human intake. Some
      public health representatives have proposed that the intense regime mandated for
      testing in Canada with 100% of the ventilation holes in the cigarette filter
      blocked, should be used for product characterisation and that it is not necessary
      that it should reflect general human smoking behaviour. We believe that this is a
      flawed approach because our studies and those of other workers demonstrate that
      the conditions generated in the cigarette when using this intense machine smoking
      regime are extreme in comparison to the conditions found for regimes based more
      realistically on human smoking. In this paper, we provide data to show that
      smokers modify their smoking intensity over the course of smoking in response to
      changes in draw resistance, smoke concentrations and smoke temperatures. We
      compare changes in and interactions between these parameters during puffing when
      smoking cigarettes of different designs. Cigarettes were smoked using various
      machine smoking regimes previously proposed for smoke testing as well as a regime
      based on human smoking data from an 'in-house' study. Puffing parameters were
      derived from this study to represent the 'average smoker' under laboratory
      conditions and equivalent to the 90th percentile when the studied smokers smoked
      under natural conditions. Biomarker data from human uptake studies have shown
      that ventilation is an effective cigarette design tool to reduce total smoke
      constituent uptake in humans so demonstrating that any blocking of filter
      ventilation is far from 100%. Likewise, this current work also shows how smokers
      modify their smoking behaviour in ways not well reflected by the 100% ventilation
      blocking regime. It seems logical that any machine smoking regime chosen for
      future product regulation should reflect these findings for it to have valid
      public health relevance. In addition, it seems misguided to discourage product
      design features, such as ventilation, which clearly can provide products with
      reduced human smoke exposure, just to maintain the dogma, counter to the
      scientific evidence, that there must be a regulatory regime with 100% ventilation
      blocking.

PMID- 20807559
TI  - Carcinogenic PAH in waterpipe charcoal products.
AB  - Because narghile waterpipe (shisha, hooka) smoking normally involves the use of
      burning charcoal, smoke inhaled by the user contains constituents originating
      from the charcoal in addition to those from the tobacco. We have previously found
      that charcoal accounts for most of the polyaromatic hydrocarbons (PAH) and carbon
      monoxide in the smoke of the waterpipe, both of which are present in alarming
      quantities. Because charcoal manufacturing conditions favor formation of PAH, it
      is reasonable to assume that charcoal sold off the shelf may be contaminated by
      PAH residues. These residues may constitute a significant fraction of the PAH
      inhaled by the waterpipe user and those in her/his vicinity. We measured PAH
      residues on three kinds of raw waterpipe charcoal sampled from Beirut stores and
      cafes. We found that PAH residues in raw charcoal can account for more than half
      of the total PAH emitted in the mainstream and sidestream smoke, and about one
      sixth of the carcinogenic 5- and 6-ring PAH compounds. Total PAH content of the
      three charcoal types varied systematically by a factor of six from the charcoal
      with the least to the greatest PAH residue. These findings indicate the
      possibility of regulating charcoal carcinogen content.

PMID- 20807560
TI  - Toxicology study of vanillin on rats via oral and intra-peritoneal
      administration.
AB  - Vanillin is useful as anti-sickle cell anemia, anti-mutagen and anti-bacteria
      agent. However, vanillin must be administered at high concentration and cannot be
      oxidized by the upper gastrointestinal track of patients to be medically
      effective. In this study, we assessed the toxic effect of vanillin when
      administered in an un-oxidized form at high concentrations (150 and 300 mg/kg)
      via oral and intra-peritoneal injection. It was found that 300 mg/kg vanillin
      injection caused the rats to be unconscious without exerting any toxic effect on
      blood cells, kidney and liver. Besides, it showed blood protective property.
      Further analysis with GenomeLab GeXP genetic system on brain tissues showed that
      the expression of most xenobiotic metabolism, cell progression, tumor suppressor,
      DNA damage and inflammation genes were maintained at normal level. However, the
      expression of a few xenobiotic metabolism, cell cycle arrest and apoptosis genes
      were up-regulated by 5% ethanol injection. Nevertheless, when 5% ethanol was
      injected with the presence of vanillin, the expression was back to normal level.
      It is postulated that vanillin might have neuro-protective property. In
      conclusion, vanillin is not toxic at high concentration in both oral and intra
      peritoneal injection and could provide blood and brain protective properties.

PMID- 20807561
TI  - Neurogenesis in the R6/2 mouse model of Huntington's disease is impaired at the
      level of NeuroD1.
AB  - Adult neurogenesis is impaired in the hippocampus of transgenic R6 mouse models
      of Huntington's disease (HD). The phenotypes of R6 transgenic mice mimic several
      symptoms and signs of the disease (Li et al., 2005). They exhibit neurological
      and endocrine changes resembling some symptoms seen in humans. The reduction in
      neurogenesis is only apparent in the dentate gyrus as the number of newborn
      neurons in the subventricular zone, and olfactory bulb, is normal in R6 mice. The
      mechanism(s) underlying the reduction in hippocampal neurogenesis is still not
      fully understood. Here we show that the number of neuroblasts, but not granule
      neuron progenitors, is greatly reduced in 11-week old transgenic mice compared
      with wild-type (WT) controls. We demonstrate that NeuroD1 expression is reduced
      in the hippocampus. This is coupled to a decreased expression of downstream
      markers doublecortin and calretinin in maturing neurons. Taken together, our
      results suggest that mutant huntingtin (Htt) causes alterations of proteins
      expression in hippocampal progenitors, which might contribute to cognitive
      deficits in Huntington's disease.

PMID- 20807563
TI  - New perspectives for Lactobacilli exopolysaccharides.
AB  - Lactobacilli have the ability to produce different kinds of exopolysaccharides
      (EPS) exhibiting a wide diversity of structures. EPS are classified, according to
      their composition into homopolysaccharides and heteropolysaccharides. One of
      their most described applications is their utilization as texturing agents
      naturally synthesized in the fermented food products. Nowadays, in regard to
      demand of modern consumers focusing towards safe and healthy food without
      additives, new perspectives of development appear for these biopolymers. The GRAS
      (Generally Recognized As Safe) and probiotic status of some lactobacilli give to
      them more preference for consumable EPS production. The main drawbacks limiting
      their industrial expansion are their low yields of production and the validation
      of their healthy allegations. Moreover, the texturing role of these
      exopolysaccharides, notably in dairy products, is actually a controversial issue.
      This review focuses on the novel ways of EPS production employing Lactobacillus
      spp. and their potential as nutraceuticals.

PMID- 20807562
TI  - Changes in and dorsal to the rat suprachiasmatic nucleus during early pregnancy.
AB  - Circadian rhythms in behavior and physiology change as female mammals transition
      from one reproductive state to another. The mechanisms responsible for this
      plasticity are poorly understood. The suprachiasmatic nucleus (SCN) of the
      hypothalamus contains the primary circadian pacemaker in mammals, and a large
      portion of its efferent projections terminate in the ventral subparaventricular
      zone (vSPZ), which also plays important roles in rhythm regulation. To determine
      whether these regions might mediate changes in overt rhythms during early
      pregnancy, we first compared rhythms in Fos and Per2 protein expression in the
      SCN and vSPZ of diestrous and early pregnant rats maintained in a 12:12-h
      light/dark (LD) cycle. No differences in the Fos rhythm were seen in the SCN
      core, but in the SCN shell, elevated Fos expression was maintained throughout the
      light phase in pregnant, but not diestrous, rats. In the vSPZ, the Fos rhythm was
      bimodal in diestrous rats, but this rhythm was lost in pregnant rats. Peak Per2
      expression was phase-advanced by 4 h in the SCN of pregnant rats, and some
      differences in Per2 expression were found in the vSPZ as well. To determine
      whether differences in Fos expression were due to altered responsivity to light,
      we next characterized light-induced Fos expression in the SCN and vSPZ of
      pregnant and diestrous rats in the mid-subjective day and night. We found that
      the SCN core of the two groups responded in the same way at each time of day,
      whereas the rhythm of Fos responsivity in the SCN shell and vSPZ differed between
      diestrous and pregnant rats. These results indicate that the SCN and vSPZ are
      functionally re-organized during early pregnancy, particularly in how they
      respond to the photic environment. These changes may contribute to changes in
      overt behavioral and physiological rhythms that occur at this time.

PMID- 20807564
TI  - An oxidative environment promotes growth of Mycobacterium abscessus.
AB  - Mycobacterium abscessus infections, particularly those causing chronic lung
      diseases, are becoming more prevalent worldwide. M. abscessus infections are
      difficult to treat because of antibiotic resistance. Thus, new treatment options
      are urgently needed. M. abscessus is an intracellular pathogen that primarily
      infects macrophages and fibroblasts. Because this bacterium has only recently
      been identified as a separate species, very little is known about M. abscessus
      host interactions and how M. abscessus growth is regulated. Oxidative stress has
      long been shown to inhibit the growth of bacterial organisms. However, some
      intracellular bacteria, such as Mycobacterium tuberculosis, grow well in
      oxidizing environments. In this study, we show that M. abscessus infection causes
      the host cell environment to become more oxidizing. Furthermore, we show that a
      more oxidizing environment leads to enhanced growth of M. abscessus inside
      macrophages. In the presence of antioxidants, MnTE-2-PyP (chemical name:
      manganese(II) meso-tetrakis-(N-methylpyridinium-2-yl) porphyrin) or N-acetyl-l
      cysteine, M. abscessus growth is inhibited. These results lead us to postulate
      that antioxidants may aid in the treatment of M. abscessus infections.

PMID- 20807566
TI  - CK2 inhibition induces apoptosis via the ER stress response.
AB  - Protein kinase CK2 is a ubiquitously expressed serine/threonine kinase consisting
      of two catalytic alpha/alpha' and two regulatory beta subunits. Expression of CK2
      is highly elevated in tumor cells where it protects cells from apoptosis.
      Accordingly inhibition of CK2 is known to induce programmed cell death, making it
      a promising target for cancer therapy. In the present study we investigated
      apoptosis induction by the CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) in
      prostate tumor cells. In contrast to PC-3 cells LNCaP cells respond to CK2
      inhibition with apoptosis. Most interestingly we found the mitochondrial pathway
      induced in LNCaP as well as in PC-3 cells as monitored by down-regulation of bcl
      2 and subsequent cytochrome c release. In both cell lines activation of caspase 9
      was not detected. Instead, an activation of the endoplasmic reticulum (ER) stress
      response in LNCaP cells after treatment with the CK2 inhibitor TBB was found. We
      show that this ER stress response led to an up-regulation of the death receptor
      DR5 and subsequent apoptosis in LNCaP cells.

PMID- 20807567
TI  - Ligand-induced internalization of TNF receptor 2 mediated by a di-leucin motif is
      dispensable for activation of the NFkappaB pathway.
AB  - Endocytosis is an important mechanism to regulate tumor necrosis factor (TNF)
      signaling. In contrast to TNF receptor 1 (TNFR1; CD120a), the relevance of
      receptor internalization for signaling as well as the fate and route of
      internalized TNF receptor 2 (TNFR2; CD120b) is poorly understood. To analyze the
      dynamics of TNFR2 signaling and turnover at the plasma membrane we established a
      human TNFR2 expressing mouse embryonic fibroblast cell line in a TNFR1(-/
      )/TNFR2(-/-) background. TNF stimulation resulted in a decrease of constitutive
      TNFR2 ectodomain shedding. We hypothesized that reduced ectodomain release is a
      result of TNF/TNFR2 complex internalization. Indeed, we could demonstrate that
      TNFR2 was internalized together with its ligand and cytoplasmic binding partners.
      Upon endocytosis the TNFR2 signaling complex colocalized with late
      endosome/lysosome marker Rab7 and entered the lysosomal degradation pathway.
      Furthermore, we identified a di-leucin motif in the cytoplasmic part of TNFR2
      suggesting clathrin-dependent internalization of TNFR2. Internalization defective
      TNFR2 mutants are capable to signal, i.e. activate NFkappaB, demonstrating that
      the di-leucin motif dependent internalization is dispensable for this response.
      We therefore propose that receptor internalization primarily serves as a negative
      feed-back to limit TNF responses via TNFR2.

PMID- 20807565
TI  - Mouse brain plasmalogens are targets for hypochlorous acid-mediated modification
      in vitro and in vivo.
AB  - Plasmalogens, 1-O-alk-1'-enyl-2-acyl-sn-glycerophospholipids, are significant
      constituents of cellular membranes and are essential for normal brain
      development. Plasmalogens, which contain a vinyl ether bond at the sn-1 position,
      are preferential targets for hypochlorous acid (HOCl), generated by
      myeloperoxidase (MPO) from H(2)O(2) and chloride ions. Because MPO is implicated
      in neurodegeneration, this study pursued two aims: (i) to investigate the
      reactivity of mouse brain plasmalogens toward HOCl in vitro and (ii) to obtain in
      vivo evidence for MPO-mediated brain plasmalogen modification. Liquid
      chromatography coupled to hybrid linear ion trap-Fourier transform-ion cyclotron
      resonance mass spectrometry revealed plasmalogen modification in mouse brain
      lipid extracts at lower HOCl concentrations as observed for diacylphospholipids,
      resulting in the generation of 2-chloro fatty aldehydes and lysophospholipids.
      Lysophosphatidylethanolamine accumulation was transient, whereas
      lysophosphatidylcholine species containing saturated acyl residues remained
      stable. In vivo, a single, systemic endotoxin injection resulted in upregulation
      of cerebral MPO mRNA levels to a range comparable to that observed for tumor
      necrosis factor-alpha and cyclooxygenase-2. This inflammatory response was
      accompanied by a significant decrease in several brain plasmalogen species and
      concomitant in vivo generation of 2-chlorohexadecanal. The present findings
      demonstrate that activation of the MPO-H(2)O(2)-chloride system under
      neuroinflammatory conditions results in oxidative attack of the total cerebral
      plasmalogen pool. As this lipid class is indispensable for normal neuronal
      function, HOCl-mediated plasmalogen modification is likely to compromise normal
      synaptic transmission.

PMID- 20807568
TI  - Activation of the JNK signalling pathway by macrophage migration inhibitory
      factor (MIF) and dependence on CXCR4 and CD74.
AB  - c-Jun N-terminal kinase (JNK) is a member of the mitogen-activated protein kinase
      (MAPK) family and controls essential processes such as inflammation, cell
      differentiation, and apoptosis. JNK signalling is triggered by extracellular
      signals such as cytokines and environmental stresses. Macrophage migration
      inhibitory factor (MIF) is a pleiotropic pro-inflammatory cytokine with chemokine
      like functions in leukocyte recruitment and atherosclerosis. MIF promotes MAPK
      signalling through ERK1/2, while it can either activate or inhibit JNK
      phosphorylation, depending on the cell type and underlying stimulation context.
      MIF activities are mediated by non-cognate interactions with the CXC chemokine
      receptors CXCR2 and CXCR4 or by ligation of CD74, which is the cell surface
      expressed form of the class II invariant chain. ERK1/2 signalling stimulated by
      MIF is dependent on CD74, but the receptor pathway involved in MIF activation of
      the JNK pathway is unknown. Here we comprehensively characterize the stimulatory
      effect of MIF on the canonical JNK/c-Jun/AP-1 pathway in fibroblasts and T cell
      lines and identify the upstream signalling components. Physiological
      concentrations of recombinant MIF triggered the phosphorylation of JNK and c-Jun
      and rapidly activated AP-1. In T cells, MIF-mediated activation of the JNK
      pathway led to upregulated gene expression of the inflammatory chemokine CXCL8.
      Activation of JNK signalling by MIF involved the upstream kinases PI3K and SRC
      and was found to be dependent on CXCR4 and CD74. Together, these data show that
      the CXCR4/CD74/SRC/PI3K axis mediates a rapid and transient activation of the JNK
      pathway as triggered by the inflammatory cytokine MIF in T cells and fibroblasts.

PMID- 20807569
TI  - Down-regulation of cyclic nucleotide phosphodiesterase PDE1A is the key event of
      p73 and UHRF1 deregulation in thymoquinone-induced acute lymphoblastic leukemia
      cell apoptosis.
AB  - Thymoquinone (TQ), the active principle of Nigella sativa black seeds, has anti
      proliferative properties on numerous cancer cell types. Others and we have
      previously reported that TQ acts as agent that triggers cell cycle arrest and
      apoptosis through either a p53- or p73-dependent pathway. However, the immediate
      targets recruited upon TQ-induced cytotoxicity have not yet been clearly
      identified. We therefore asked whether cyclic nucleotide phosphodiesterases
      (PDEs) could be involved in TQ-triggered pro-apoptotic reactivity; PDEs are
      regulators of intracellular levels of cyclic nucleotides and therefore can
      modulate cAMP and cGMP-dependent cell death pathways. Our results showed that TQ
      specifically repressed PDE1A expression in the acute lymphoblastic leukemia
      Jurkat cell line. This effect is concomitant with the previously described
      sequential deregulation of the expression of the tumor suppressor protein p73 and
      the epigenetic integrator UHRF1 (Ubiquitin-like, PHD Ring Finger 1).
      Interestingly, RNA-interference knock-down of PDE1A expression as well as
      decreased PDE1A expression induced growth inhibition of Jurkat cells, cell cycle
      arrest and apoptosis through an activation of p73 and a repression of UHRF1.
      Conversely, PDE1A re-expression counteracted the cellular pro-apoptotic effects
      of TQ in association with a p73 repression and UHRF1 re-expression. Altogether,
      our results show that TQ induced an initial down-regulation of PDE1A with a
      subsequent down-regulation of UHRF1 via a p73-dependent mechanism. This study
      further proposes that PDE1A might be involved in the epigenetic code inheritance
      by regulating, via p73, the epigenetic integrator UHRF1. Our findings also
      suggest that a forced inhibition of PDE1A expression might be a new therapeutic
      strategy for the management of acute lymphoblastic leukemia.

PMID- 20807570
TI  - The role and regulation of GDF11 in Smad2 activation during tailbud formation in
      the Xenopus embryo.
AB  - A key role for phosphorylation of Smad2 by TGFbeta superfamily ligands in the
      axial patterning of early embryos is well established. The regulation and role of
      Smad2 signaling in post-neurula embryonic patterning, however, is less well
      understood. While a variety of TGFbeta superfamily ligands are implicated in
      various stages of anterior-posterior patterning, the ligand GDF11 has been shown
      to have a particular role in post-gastrula patterning in the mouse. Mouse GDF11
      is specifically localized to the developing tail and is essential for normal
      posterior axial patterning. Mature GDF11 ligand is inhibited by its own
      prodomain, and extracellular proteolysis of this prodomain is thought to be
      necessary for GDF11 activity. The contribution of this proteolytic regulatory
      mechanism to Smad activation during embryogenesis in vivo, and to the development
      of posterior pattern, has not been characterized. We investigate here the role of
      Xenopus GDF11 in the activation of Smad2 during the development of tailbud-stage
      embryos, and the role of this activation in larval development. We also
      demonstrate that the activity of BMP-1/Tolloid-like proteases is necessary for
      the normal GDF11-dependent activation of Smad2 phosphorylation during post
      gastrula development. These data demonstrate that GDF11 has a central role in the
      activation of Smad2 phosphorylation in tailbud stage Xenopus embryos, and provide
      the first evidence that BMP-1/Tolloid-mediated prodomain cleavage is important
      for activation of GDF11 in vivo.

PMID- 20807572
TI  - The T-box brain 1 (Tbr1) transcription factor inhibits astrocyte formation in the
      olfactory bulb and regulates neural stem cell fate.
AB  - The T-box brain 1 (Tbr1) gene encodes a transcription factor necessary for the
      maintenance and/or differentiation of glutamatergic cells in the olfactory bulb
      (OB) and cortex, although its precise function in the development of
      glutamatergic neurons is not known. Furthermore, Tbr1 has not been reported to
      regulate the formation of glial cells. We show that Tbr1 is expressed during the
      initial stages in the generation of glutamatergic mitral neurons from dividing
      progenitors in the E12.5 mouse OB. Retroviral-mediated overexpression of Tbr1 in
      cultured embryonic and adult OB stem cells (OBSC) produces a marked increase in
      the number of TuJ1(+) neurons (including VGLUT1(+) glutamatergic and GABA(+)
      neurons) and O4(+) oligodendrocytes. Moreover, transduction of Tbr1 inhibits the
      production of GFAP(+) astrocytes from both cultured OBSC and dividing progenitor
      cells in vivo. These results show that the expression of Tbr1 in neural stem and
      progenitor cells prevents them from following an astrocyte fate during OB
      development. Our findings suggest that the transduction of Tbr1 into neural stem
      cells could be useful to increase the production of neurons and oligodendrocytes
      in studies of neuroregeneration.

PMID- 20807571
TI  - Fibronectin and integrin alpha 5 play essential roles in the development of the
      cardiac neural crest.
AB  - Cardiac neural crest (CNC) plays a requisite role during cardiovascular
      development and defects in the formation of CNC-derived structures underlie
      several common forms of human congenital birth defects. Migration of the CNC
      cells to their destinations as well as expansion and maintenance of these cells
      are important for the normal development of the cardiac outflow tract and aortic
      arch arteries; however, molecular mechanisms regulating these processes are not
      well-understood. Fibronectin (FN) protein is present along neural crest migration
      paths and neural crest cells migrate when plated on FN in vitro; therefore, we
      tested the role of FN during the development of the CNC in vivo. Our analysis of
      the fate of the neural crest shows that CNC cells reach their destinations in the
      branchial arches and the cardiac outflow tract in the absence of FN or its
      cellular receptor integrin alpha5beta1. However, we found that FN and integrin
      alpha5 modulate CNC proliferation and survival, and are required for the presence
      of normal numbers of CNC cells at their destinations.

PMID- 20807574
TI  - The impact of pre-analytical processing on staining quality for H&E, dual hapten,
      dual color in situ hybridization and fluorescent in situ hybridization assays.
AB  - With the advent of personalized medicine, anatomic pathology-based molecular
      assays, including in situ hybridization (ISH) and mRNA detection tests, are
      performed routinely in many laboratories and have increased in their clinical
      importance and complexity. These assays require appropriately fixed tissue
      samples that preserve both nucleic acid targets and histomorphology to ensure
      reliable test results for determining patient treatment options. However, all
      aspects of tissue processing, including time until tissue fixation, type of
      fixative, duration of fixation, post-fixation treatments, and sectioning of the
      sample, impact the staining results. ASCO/CAP has issued pre-analytical
      guidelines to standardize tissue processing for HER2 testing in breast carcinoma
      specimens: 10% neutral-buffered formalin (NBF) with a fixation time from at least
      6 to 48h [1]. Often, this recommendation is not followed to the detriment of
      staining results [2]. In this paper, we used a human breast carcinoma cell line
      (MCF7) generated as xenograft tumors as a model system to analyze the effects of
      different pre-analytical conditions on ISH staining. We performed H&E, FISH and
      dual colorimetric HER2 ISH assays using specimens fixed across a range of times
      in six different commonly used fixatives. Additionally, we investigated the
      effects of varying tissue section thickness, which also impacted the quality of
      ISH staining. Finally, we evaluated the effects of three different decalcifying
      solutions on human breast specimens, typically a treatment that occurs post
      fixation for evaluating metastases to bone. The results indicate that time and
      type of fixation treatment, as well as appropriate tissue thickness and post
      fixation treatment, all contribute to the quality of ISH staining results. Our
      data support the ASCO/CAP recommendations for standardized tissue processing (at
      least 6h in formalin-based fixatives and 4MUm section thickness) and indicate
      that certain fixatives and post-fixative treatments are detrimental to molecular
      staining results.

PMID- 20807573
TI  - Ca2+/calmodulin-dependent protein kinase II and protein kinase C activities
      mediate extracellular glucose-regulated hippocampal synaptic efficacy.
AB  - To define how extracellular glucose levels affect synaptic efficacy and long-term
      potentiation (LTP), we evaluated electrophysiological and neurochemical
      properties in hippocampal CA1 regions following alterations in glucose levels in
      the ACSF. In rat hippocampal slices prepared in ACSF with 3.5mM glucose, fEPSPs
      generated by Schaffer collateral/commissural stimulation markedly increased when
      ACSF glucose levels were increased from 3.5 to 7.0mM. The paired-pulse
      facilitation reflecting presynaptic transmitter release efficacy was
      significantly suppressed by elevation to 7.0mM glucose because of potentiation of
      the input-output relationship (I/O relationship) of fEPSPs by single pulse
      stimulation. Prolonged potentiation of fEPSPs by elevation to 7.0mM glucose
      coincided with increased autophosphorylation both of Ca(2+)/calmodulin-dependent
      protein kinase II (CaMKII) and protein kinase Calpha (PKCalpha). The increased
      I/O relationship of fEPSPs was also associated with markedly increased synapsin I
      phosphorylation by CaMKII. Transmitter-evoked postsynaptic currents were also
      measured in CA1 neurons by electrophoretical application of NMDA and AMPA to the
      apical dendrites of pyramidal neurons. NMDA- and AMPA-evoked currents were
      significantly augmented by elevation to 7.0mM. Notably, high frequency
      stimulation of the Schaffer collateral/commissural pathway failed to induce LTP
      in the CA1 region at 3.5mM glucose but LTP was restored dose-dependently by
      increasing glucose levels to 7.0 and 10.0mM. LTP induction in the presence of
      7.0mM glucose was closely associated with further increases in CaMKII
      autophosphorylation without changes in PKCalpha autophosphorylation. Taken
      together, CaMKII and PKC activation likely mediate potentiation of fEPSPs by
      elevated glucose levels, and CaMKII activity is also associated with LTP
      induction in the hippocampal CA1 region.

PMID- 20807575
TI  - Human striatal activation during adjustment of the response criterion in visual
      word recognition.
AB  - Results of recent computational modelling studies suggest that a general function
      of the striatum in human cognition is related to shifting decision criteria in
      selection processes. We used functional magnetic resonance imaging (fMRI) in 21
      healthy subjects to examine the hemodynamic responses when subjects shift their
      response criterion on a trial-by-trial basis in the lexical decision paradigm.
      Trial-by-trial criterion setting is obtained when subjects respond faster in
      trials following a word trial than in trials following nonword trials -
      irrespective of the lexicality of the current trial. Since selection demands are
      equally high in the current trials, we expected to observe neural activations
      that are related to response criterion shifting. The behavioural data show
      sequential effects with faster responses in trials following word trials compared
      to trials following nonword trials, suggesting that subjects shifted their
      response criterion on a trial-by-trial basis. The neural responses revealed a
      signal increase in the striatum only in trials following word trials. This
      striatal activation is therefore likely to be related to response criterion
      setting. It demonstrates a role of the striatum in shifting decision criteria in
      visual word recognition, which cannot be attributed to pure error-related
      processing or the selection of a preferred response.

PMID- 20807576
TI  - Developmental changes between ages 13 and 21 years in the extent and magnitude of
      the BOLD response during decision making.
AB  - Developmental neuroimaging results have suggested a progression in focalization
      in functional activations from childhood to adulthood. The mechanisms underlying
      this process are thought to be an age-related decrease in activation extent as
      well as an increased magnitude in task-related areas. The present study aimed to
      evaluate these notions while controlling for confounders that may bias towards
      focalization. We used adolescent subjects in small age ranges. In addition, head
      motion corrections were incorporated in statistical analyses and regions of
      interest were identified for each participant separately to overcome inter
      individual variability in anatomy and functional organization. Activation
      patterns of 13-, 17- and 21-year-old males were compared during the decision
      phase of a challenging and complex gambling paradigm. The BOLD amplitude enhanced
      with increasing age, modulated by task conditions. First, response amplitude
      during difficult, endogenous relative to exogenous decisions increased with age.
      This decision difficulty effect was most pronounced in 21-year-olds, both in
      areas associated with task execution and default mode areas. Second, deciding to
      pass as opposed to gamble exerted more effort in inferior frontal and parietal
      areas only by 13- and 17-year-olds. There was neither an age-related decrease in
      activation extent, nor any qualitative shifts in activated areas as suggested by
      the focalization hypothesis. These results suggest that although different age
      groups throughout adolescence engage similar brain areas during decision making,
      the response magnitude in these areas increases with age particularly during
      difficult task conditions, providing that confounding factors are controlled.

PMID- 20807577
TI  - A better oscillation detection method robustly extracts EEG rhythms across brain
      state changes: the human alpha rhythm as a test case.
AB  - Oscillatory activity is a principal mode of operation in the brain. Despite an
      intense resurgence of interest in the mechanisms and functions of brain rhythms,
      methods for the detection and analysis of oscillatory activity in
      neurophysiological recordings are still highly variable across studies. We
      recently proposed a method for detecting oscillatory activity from time series
      data, which we call the BOSC (Better OSCillation detection) method. This method
      produces systematic, objective, and consistent results across frequencies, brain
      regions and tasks. It does so by modeling the functional form of the background
      spectrum by fitting the empirically observed spectrum at the recording site. This
      minimizes bias in oscillation detection across frequency, region and task. Here
      we show that the method is also robust to dramatic changes in state that are
      known to influence the shape of the power spectrum, namely, the presence versus
      absence of the alpha rhythm, and can be applied to independent components, which
      are thought to reflect underlying sources, in addition to individual raw signals.
      This suggests that the BOSC method is an effective tool for measuring changes in
      rhythmic activity in the more common research scenario wherein state is unknown.

PMID- 20807578
TI  - Depression alters "top-down" visual attention: a dynamic causal modeling
      comparison between depressed and healthy subjects.
AB  - Using functional magnetic resonance imaging (fMRI), we recently demonstrated that
      nonmedicated patients with a first episode of unipolar major depression (MDD)
      compared to matched controls exhibited an abnormal neural filtering of irrelevant
      visual information (Desseilles et al., 2009). During scanning, subjects performed
      a visual attention task imposing two different levels of attentional load at
      fixation (low or high), while task-irrelevant colored stimuli were presented in
      the periphery. In the present study, we focused on the visuo-attentional system
      and used "Dynamic Causal Modeling" (DCM) on the same dataset to assess how
      attention influences a network of three dynamically-interconnected brain regions
      (visual areas V1 and V4, and intraparietal sulcus (P), differentially in MDD
      patients and healthy controls. Bayesian model selection (BMS) and model space
      partitioning (MSP) were used to determine the best model in each population. The
      best model for the controls revealed that the increase of parietal activity by
      high attention load was selectively associated with a negative modulation of P on
      V4, consistent with high attention reducing the processing of irrelevant colored
      peripheral stimuli. The best model accounting for the data from the MDD patients
      showed that both low and high attention levels exerted modulatory effects on P.
      The present results document abnormal effective connectivity across visuo
      attentional networks in MDD, which likely contributes to deficient attentional
      filtering of information.

PMID- 20807579
TI  - The structure and connectivity of semantic memory in the healthy older adult
      brain.
AB  - The anterior temporal lobes (ATLs) have been proposed to serve as a "hub" linking
      amodal or domain general information about the meaning of words, objects, facts
      and people distributed throughout the brain in semantic memory. The two primary
      sources of evidence supporting this proposal, viz. structural imaging studies in
      semantic dementia (SD) patients and functional imaging investigations, are not
      without problems. Similarly, knowledge about the anatomo-functional connectivity
      of semantic memory is limited to a handful of intra-operative electrocortical
      stimulation (IES) investigations in patients. Here, using principal components
      analyses (PCA) of a battery of conceptual and non-conceptual tests coupled with
      voxel based morphometry (VBM) and diffusion tensor imaging (DTI) in a sample of
      healthy older adults aged 55-85 years, we show that amodal semantic memory relies
      on a predominantly left lateralised network of grey matter regions involving the
      ATL, posterior temporal and posterior inferior parietal lobes, with prominent
      involvement of the left inferior fronto-occipital fasciculus (IFOF) and uncinate
      fasciculus fibre pathways. These results demonstrate relationships between
      semantic memory, brain structure and connectivity essential for human
      communication and cognition.

PMID- 20807580
TI  - The phylogeography of an alpine leaf beetle: divergence within Oreina elongata
      spans several ice ages.
AB  - The genetic landscape of the European flora and fauna was shaped by the ebb and
      flow of populations with the shifting ice during Quaternary climate cycles. While
      this has been well demonstrated for lowland species, less is known about high
      altitude taxa. Here we analyze the phylogeography of the leaf beetle Oreina
      elongata from 20 populations across the Alps and Apennines. Three mitochondrial
      and one nuclear region were sequenced in 64 individuals. Within an mtDNA
      phylogeny, three of seven subspecies are monophyletic. The species is chemically
      defended and aposematic, with green and blue forms showing geographic variation
      and unexpected within-population polymorphism. These warning colors show
      pronounced east-west geographical structure in distribution, but the
      phylogeography suggests repeated origin and loss. Basal clades come from the
      central Alps. Ancestors of other clades probably survived across northern Italy
      and the northern Adriatic, before separation of eastern, southern and western
      populations and rapid spread through the western Alps. After reviewing calibrated
      gene-specific substitution rates in the literature, we use partitioned Bayesian
      coalescent analysis to date our phylogeography. The major clades diverged long
      before the last glacial maximum, suggesting that O. elongata persisted many
      glacial cycles within or at the edges of the Alps and Apennines. When analyzing
      additional barcoding pairwise distances, we find strong evidence to consider O.
      elongata as a species complex rather than a single species.

PMID- 20807581
TI  - Expanded phylogeny of myxobacteria and evidence for cultivation of the
      'unculturables'.
AB  - An expanded neighbour-joining tree of myxobacteria is presented based on the
      analysis of 16S rRNA gene sequences of 101 strains (including types) representing
      3 suborders, 6 families, 20 genera, 46 species, and 12 other novel taxa. The
      distinctions amongst members of the three suborders (Sorangiineae,
      Cytobacterineae and Nannocystineae) are reaffirmed. The positions of anaerobic
      myxobacteria, novel groups (Pyxidicoccus and several Cystobacter species) in
      Cystobacterineae, the marine genera (Plesiocystis, Haliangium, Enhygromyxa), and
      two additional novel taxa ('Paraliomyxa miuraensis', brackish-water isolate) were
      together revealed for the first time. Changes in the nomenclature of several
      isolates (Polyangium vitellinum Pl vt1(T), Polyangium thaxteri Pl t3, Polyangium
      cellulosum, NOSO-1, NOCB-2, NOCB-4) are also highlighted. Suborders Sorangiineae
      and Nannocystineae hold great promise for novel strain discovery. In
      Sorangiineae, the new family Phaselicystidaceae, with a monotypic genus, was
      added. Nine additional novel taxa were discovered in this suborder for which new
      genera or even families may be erected in the near future. These taxa appear to
      represent the so-called viable but not culturable (VBNC) group of myxobacteria.
      Based on at least 4% phylogenetic distance, new clades were formed comprising of
      novel Nannocystineae and Sorangiineae isolates. Overall, the myxobacteria, on the
      basis of bracket distance, could be divided into 16 clusters, as supported by
      tree topology and a morphology-based approach.

PMID- 20807582
TI  - Sevoflurane impairs memory consolidation in rats, possibly through inhibiting
      phosphorylation of glycogen synthase kinase-3beta in the hippocampus.
AB  - Sevoflurane administration impairs memory processes in both humans and animals.
      Increasing evidence suggests that enhancement of the phosphorylation state of
      glycogen synthase kinase-3beta (GSK-3beta), as a result of acute administration
      of lithium chloride (LiCl), may enhance memory consolidation. The current
      experiments examined whether GSK-3beta phosphorylation was involved in mediating
      the memory impairing effects of posttraining sevoflurane on inhibitory avoidance
      (IA) retention. In experiment 1, adult male Sprague-Dawley rats were exposed to
      sevoflurane (0.5%, 1%, or 2%) for 2h immediately after training in a continuous
      multiple-trail IA paradigm. Sevoflurane (2% inspired) induced significant
      impairment of retention performance on a 24-h test and inhibited phosphorylation
      of GSK-3beta in the hippocampus 2h after training. In experiment 2,
      administration of LiCl (100mg/kg, intraperitoneally) 30 min before IA training
      not only blocked the sevoflurane-induced impairment of consolidation, but also
      reversed the inhibitory effect of sevoflurane on GSK-3beta phosphorylation in the
      hippocampus. Collectively, these findings support the hypothesis that sevoflurane
      exposure can impair consolidation of IA memory in rats. Sevoflurane-induced
      amnesia may be due, at least in part, to suppression of GSK-3beta phosphorylation
      in the hippocampus.

PMID- 20807583
TI  - Chronic stress, cyclic 17beta-estradiol, and daily handling influences on fear
      conditioning in the female rat.
AB  - Chronic stress and estrogens alter many forebrain regions in female rats that
      affect cognition. In order to investigate how chronic stress and estrogens
      influence fear learning and memory, we ovariectomized (OVX) female Sprague-Dawley
      rats and repeatedly injected them (s.c.) with 17beta-estradiol (E, 10 MUg/250 g
      or sesame oil vehicle, VEH). Concurrently, rats were restrained for 6 h/d/21 d
      (STR) or left undisturbed (CON). Rats were then fear conditioned with 4 tone
      footshock pairings and then after 1 h and 24 h delays, given 15 tone extinction
      trials. Regardless of E treatment, chronic stress (VEH, E) facilitated freezing
      to tone during acquisition and extinction following a 1h delay, but not during
      extinction after a 24 h delay. E did not influence freezing to tone during any
      phase of fear conditioning for either the control or chronically stressed rats,
      but did influence contextual conditioning that may have been carried
      predominately by the STR group. In the second experiment, we investigated
      "handling" influences on fear conditioning acquisition, given the disparate
      findings from the current study and previous work (Baran, Armstrong, Niren, &
      Conrad, 2010; Baran, Armstrong, Niren, Hanna, & Conrad, 2009). Female rats
      remained gonadally-intact since E did not influence tone fear conditioning.
      Indeed, brief daily handling (1-3 m/d/21 d) facilitated acquisition of fear
      conditioning in chronically stressed female rats, and either had no effect or
      slightly attenuated fear conditioning in controls. Thus, chronic stress impacts
      amygdala-mediated fear learning in both OVX- and gonadally-intact females as
      found previously in males, with handling significantly influencing these
      outcomes.

PMID- 20807584
TI  - Richard Thompson, the age-less Titan of brain science.

PMID- 20807585
TI  - The effects of midazolam and D-cycloserine on the release of glutamate and GABA
      in the basolateral amygdala of low and high anxiety rats during extinction trial
      of a conditioned fear test.
AB  - In this study, we investigated how midazolam and d-cycloserine regulate the tonic
      activity and/or phasic reactivity of brain neurotransmitter systems to fear
      evoking stimuli in rats with varying intensities of a fear response. We used a
      new animal model composed of high (HR) and low (LR) anxiety rats, selected
      according to their behaviour in the contextual fear test (i.e., the duration of a
      freezing response was used as a discriminating variable). In these rats, we
      examined the effects of both drugs on the release of glutamate and GABA in the
      basolateral amygdala (BLA) during the first extinction trial of a conditioned
      fear test. The results showed that administration of d-cycloserine (15 mg/kg,
      i.p.) significantly enhanced the inhibition of an aversive context-induced
      freezing response observed during the extinction session in HR and LR rats. In
      contrast, midazolam (0.75 mg/kg, i.p.) accelerated the attenuation of fear
      responses only in HR rats. The less anxious behaviour of LR animals given saline
      was accompanied by elevated basal levels of glutamate in the BLA, in comparison
      with HR rats, and a stronger elevation of GABA in response to contextual fear. In
      HR animals, the pretreatment of rats with d-cycloserine and midazolam
      significantly increased the local concentration of GABA and inhibited the
      expression of contextual fear. These findings suggest that animals more
      vulnerable to stress have innate deficits in brain systems that control the
      activity of the BLA mediating the central effect of stress. These results
      contribute to our understanding of observed individual differences in the effects
      of anxiolytic drugs among patients with anxiety disorders.

PMID- 20807586
TI  - Fungal secondary metabolites as modulators of interactions with insects and other
      arthropods.
AB  - Fungi share a diverse co-evolutionary history with animals, especially
      arthropods. In this review, we focus on the role of secondary metabolism in
      driving antagonistic arthropod-fungus interactions, i.e., where fungi serve as a
      food source to fungal grazers, compete with saprophagous insects, and attack
      insects as hosts for growth and reproduction. Although a wealth of studies on
      animal-fungus interactions point to a crucial role of secondary metabolites in
      deterring animal feeding and resisting immune defense strategies, causal evidence
      often remains to be provided. Moreover, it still remains an unresolved puzzle as
      to what extent the tight regulatory control of secondary metabolite formation in
      some model fungi represents an evolved chemical defense system favored by
      selective pressure through animal antagonists. Given these gaps in knowledge, we
      highlight some co-evolutionary aspects of secondary metabolism, such as induced
      response, volatile signaling, and experimental evolution, which may help in
      deciphering the ecological importance and evolutionary history of secondary
      metabolite production in fungi.

PMID- 20807587
TI  - Can biologic pacemakers respond to physiologic emotional arousal?

PMID- 20807588
TI  - Yeast mitochondrial DNA polymerase is a highly processive single-subunit enzyme.
AB  - Polymerase gamma is solely responsible for fast and faithful replication of the
      mitochondrial genome. High processivity of the polymerase gamma is often achieved
      by association of the catalytic subunit with accessory factors that enhance its
      catalytic activity and/or DNA binding. Here we characterize the intrinsic
      catalytic activity and processivity of the recombinant catalytic subunit of yeast
      polymerase gamma, the Mip1 protein. We demonstrate that Mip1 can efficiently
      synthesize DNA stretches of up to several thousand nucleotides without
      dissociation from the template. Furthermore, we show that Mip1 can perform DNA
      synthesis on double-stranded templates utilizing a strand displacement mechanism.
      Our observations confirm that in contrast to its homologues in other organisms,
      Mip1 can function as a single-subunit replicative polymerase.

PMID- 20807589
TI  - Regulatory T cells: the suppressor arm of the immune system.
AB  - The existence of a population of lymphocytes with suppressor activity able to
      inhibit immune responses has been widely studied. The greatest advances were made
      when researchers proposed markers, such as CD25 and Foxp3, for identifying those
      suppressor T cells. Regulatory T cells (Tregs) represent approximately 10% of the
      CD4 T cells and are able to suppress the immune responses to self and foreign
      antigens. Tregs can develop and acquire a suppressor phenotype in the thymus
      (natural Tregs) or be induced in the periphery followed certain activation and
      antigen presentations conditions (induced Tregs). These cells can suppress the
      immunological system by two principal pathways: the direct suppression of the
      target cells by cell-contact, and by the secretion of suppressor cytokines. This
      review summarizes the published data on Tregs and its suggested role in various
      states of health and disease.

PMID- 20807590
TI  - Modulation of autoimmunity with artificial peptides.
AB  - The loss of immune tolerance to self antigens leads to the development of
      autoimmune responses. Since self antigens are often multiple and/or their
      sequences may be known, one approach to restore immune tolerance uses synthetic
      artificial peptides that interfere or compete with self peptides in the networks
      of cellular interactions that drive the autoimmune process. This review describes
      the rationale behind the use of artificial peptides in autoimmunity and their
      mechanisms of action. Examples of use of artificial peptides in preclinical
      studies and in the management of human autoimmune diseases are provided.

PMID- 20807591
TI  - Bioassays for TSH-receptor autoantibodies: an update.
AB  - Immunoglobulins in patients with Graves' disease (GD) that modulate the thyroid
      stimulating hormone receptor (TSH-R) do so via stimulating cAMP dependent signals
      (TSI), blocking TSH or inhibition of TSH-receptor activation (TBI) or inducing
      apoptotic signals. These functional immunoglobulins represent powerful biomarkers
      of anti-self reactivity in the thyroid and systemic tissues that harbor TSH-R
      expressing target cells. TSI on thyrocytes induce hyperthyroidism, and TSI on TSH
      R fibroblasts of orbital muscles, skin and heart provoke the release of cytokines
      and antigen-specific T-cell responses leading to systemic inflammation. Bioassays
      of anti-TSH-R autoantibodies provide decisive information on GD activity. This
      review examines the past and present bioassays in GD. The critical goal of cell
      based anti-TSH-R autoantibody bioassays, to identify the pathogenic
      immunoglobulins in GD under robust and standardized conditions suitable for
      routine clinical laboratory practice, is discussed.

PMID- 20807592
TI  - Structural analysis and molecular modeling of the RvH2-e functional unit of
      Rapana venosa hemocyanin.
AB  - Rapana venosa hemocyanin (RvH), a circulating glycoprotein of the marine snail,
      has a complex structure. To provide details on the stability of the protein, one
      functional unit, RvH2-e, was compared with the native molecule and the structural
      subunits, RvH1 and RvH2, via pH-T diagrams, typical phase portraits for stability
      and denaturation reversibility. By analyzing the T transition curves of RvH2-e at
      different pH values, several parameters of the thermodynamic functions were
      obtained. Increasing the temperature from 25 degrees C to 55 degrees C, the
      reversibility of the molecule of protein also increases, opening a reversibility
      window within the range of pH 4.0-8.0. On analyzing the pH transition curves, the
      start of the acid denaturation (below pH 6) and alkaline denaturation (above pH
      9) was determined to be between 20 degrees C and 35 degrees C. For this range,
      the thermodynamic functions DeltaH degrees  and DeltaG degrees  for a standard
      temperature of 25 degrees C were calculated.

PMID- 20807593
TI  - Hydroxyapatite/biodegradable poly(L-lactide-co-epsilon-caprolactone) composite
      microparticles as injectable scaffolds by a Pickering emulsion route.
AB  - Hydroxyapatite (HAp)/biodegradable poly(L-lactide-co-epsilon-caprolactone)
      (P(LA/CL)) composite microparticles were fabricated as an injectable scaffold via
      the Pickering emulsion route in the absence of any molecular surfactants. A
      stable oil in water emulsion was obtained using water dispersed HAp nanocrystals
      as the particulate emulsifier and a dichloromethane (CH(2)Cl(2)) solution of
      P(LA/CL) as the oil phase. The concentration-viscosity relationship of the
      P(LA/CL) solution and its influence on the formation of a stable emulsion were
      investigated. The dependence of homogenization on the concentration of the
      P(LA/CL) solution and shear speed of homogenization was also evaluated.
      HAp/P(LA/CL) microparticles of various morphologies, such as plates and spheres,
      or with various surface morphologies were realized through adjustment of the
      concentration and composition of the P(LA/CL) solution. The microparticles were
      observed by optical microscopy and scanning electronic microscopy and their size
      distributions measured using a microparticle size analyzer. The weight
      percentages of HAp nanocrystals on the HAp/P(LA/CL) microparticles of different
      average sizes were measured by thermogravimetric analysis.

PMID- 20807594
TI  - Oriented bioactive glass (13-93) scaffolds with controllable pore size by
      unidirectional freezing of camphene-based suspensions: Microstructure and
      mechanical response.
AB  - Scaffolds of 13-93 bioactive glass (composition 6.0 Na2O, 7.9 K2O, 7.7 MgO, 22.1
      CaO, 1.7 P2O5, 54.6 SiO2 (mol.%)) containing oriented pores of controllable
      diameter were prepared by unidirectional freezing of camphene-based suspensions
      (10 vol.% particles) on a cold substrate (-196  degrees C or 3  degrees C). By
      varying the annealing time (0-72 h) to coarsen the camphene phase, constructs
      with the same porosity (86 +/- 1%) but with controllable pore diameters (15-160
      MUm) were obtained after sublimation of the camphene. The pore diameters had a
      self-similar distribution that could be fitted by a diffusion-controlled
      coalescence model. Sintering (1 h at 690  degrees C) was accompanied by a
      decrease in porosity and pore diameter, the magnitude of which depended on the
      pore size of the green constructs, giving scaffolds with a porosity of 20-60% and
      average pore diameter of 6-120 MUm. The compressive stress vs. deformation
      response of the sintered scaffolds in the orientation direction was linear,
      followed by failure. The compressive strength and elastic modulus in the
      orientation direction varied from 180 MPa and 25 GPa (porosity=20%) to 16 MPa and
      4 GPa (porosity=60%), respectively, which were 2-3 times larger than the values
      in the direction perpendicular to the orientation. The potential use of these 13
      93 bioactive glass scaffolds for the repair of large defects in load-bearing
      bones, such as segmental defects in long bones, is discussed.

PMID- 20807595
TI  - Role of wettability and nanoroughness on interactions between osteoblast and
      modified silicon surfaces.
AB  - Development of new biomaterials is a constant in regenerative medicine. A
      biomaterial's surface properties, such as wettability, roughness, surface energy,
      surface charge, chemical functionalities and composition, are determinants of
      cell adhesion and subsequent tissue behavior. Thus, the main aim of this study
      was to analyze the correlation between changes in wettability without
      topographical variation and the response of osteoblast-like cells. For this
      purpose oxidized silicon surfaces were methylated to different degrees.
      Additionally, the influence of nanoroughness, and the subsequent effect of
      hysteresis on cell behavior, was also analyzed. In this case oxidized silicon
      pieces were etched with caustic solutions to produce different degrees of
      nanoroughness. Axisymmetric drop-shape analysis and atomic force microscopy
      confirmed that the proposed surface treatments increased the nanometer roughness
      and/or the water contact angles. MG-63 osteoblast-like cells were cultured on the
      altered surfaces to study proliferation, and for ultrastructural analysis and
      immunocytochemical characterization. Increasing the nanometer surface roughness
      or water contact angle enhanced osteoblast behavior in terms of cell morphology,
      proliferation and immunophenotype, the effect provoked by methylation being more
      significant than that caused by nanoroughness.

PMID- 20807596
TI  - Adhesive substrates modulate the activation and stimulatory capacity of non-obese
      diabetic mouse-derived dendritic cells.
AB  - It is known that adsorbed adhesive proteins on implanted biomaterials modulate
      inflammatory responses; however, modulation of dendritic cell (DC) responses upon
      interaction with adhesive proteins has only begun to be characterized. DCs are
      specialized antigen-presenting cells that modulate both innate and adaptive
      immune responses. Previously we have shown that the activation and stimulatory
      capacity of DCs derived from C57BL6/j mice is differentially modulated by
      adhesive substrates. Here we extend our investigation of adhesive substrate
      modulation of DC responses to consider the case where the DCs had maturational
      defects associated with diabetes. Understanding the adhesive responses of DCs in
      diabetics is potentially important for immunotherapy and tissue engineering
      applications. In this work we use the non-obese diabetic (NOD) mouse, an
      established animal model for type 1 diabetes, to generate DCs (NOD-DCs). We
      demonstrate that NOD-DCs cultured on different adhesive substrates (collagen,
      fibrinogen, fibronectin, laminin, vitronectin, albumin and serum) respond with
      substrate-dependent modulation of the surface expression of the stimulatory
      molecule MHC-II and the co-stimulatory molecules CD80 and CD86 and production of
      the cytokines IL-12p40 and IL-10. Furthermore, the capacity of NOD-DCs to
      stimulate CD4(+) T-cell proliferation and cytokine production (IL-4 and IFN
      gamma) showed substrate-dependent modulation. Specifically, NOD-DCs cultured on
      vitronectin induced the highest IL-12p40 production, whereas collagen induced the
      highest IL-10 production. Dendritic cells cultured on collagen, fibrinogen and
      serum-coated substrates stimulated the highest CD4(+) T-cell proliferation. It
      was further determined that DCs cultured on vitronectin induced the highest
      percent population of IL-4-producing T-cells and DCs cultured on a fibronectin
      coated substrate induced the highest expression of IFN-gamma in T-cells.
      Pearson's correlation analysis revealed high correlations between T-cell
      proliferation and DC expression level of CD80 and T-cell production of IL-4 and
      DC production of IL-10. This demonstration of substrate-based control of NOD-DC
      activatory and stimulatory capacity, distinct from non-diabetic B6-DC responses,
      establishes the field of adhesive modulation of immune cell responses and informs
      the rational design of biomaterials for patients with type 1 diabetes.

PMID- 20807598
TI  - Discovery of putative pancreatic cancer biomarkers using subcellular proteomics.
AB  - Pancreatic cancer (PC) is a highly aggressive disease that frequently remains
      undetected until it has progressed to an advanced, systemic stage. Successful
      treatment of PC is hindered by the lack of early detection. The application of
      proteomic analysis to PC combined with subcellular fractionation has introduced
      new possibilities in the field of biomarker discovery. We utilized matched pairs
      of pancreas tumor and non-tumor pancreas from patients undergoing tumor
      resection. The tissues were treated to obtain cellular protein fractions
      corresponding to cytosol, membrane, nucleus and cytoskeleton. The fractions were
      then separated by molecular weight and digested with trypsin, followed by liquid
      chromatography and tandem mass spectrometry. The spectra obtained were searched
      using Sequest engine and combined into a single analysis file to obtain a semi
      quantitative number, spectral count, using Scaffold software. We identified 2393
      unique proteins in non-tumor and cancer pancreas. Utilizing PLGEM statistical
      analysis we determined 104 proteins were significantly changed in cancer. From
      these, we further validated four secreted proteins that are up-regulated in
      cancer and have potential for development as minimally-invasive diagnostic
      markers. We conclude that subcellular fractionation followed by gel
      electrophoresis and tandem mass spectrometry is a powerful strategy for
      identification of differentially expressed proteins in pancreatic cancer.

PMID- 20807597
TI  - Three-dimensional poly(1,8-octanediol-co-citrate) scaffold pore shape and
      permeability effects on sub-cutaneous in vivo chondrogenesis using primary
      chondrocytes.
AB  - The objective of this study was to evaluate the coupled effects of three
      dimensional poly(1,8-octanediol-co-citrate) (POC) scaffold pore shape and
      permeability on chondrogenesis using primary chondrocytes in vivo. Chondrogenesis
      was characterized as cartilage matrix formation by sulfated glycosaminoglycan
      (sGAG) quantification, relative mRNA expression of the cartilage-related proteins
      collagen types I, II and X, aggrecan and matrix metalloproteinases 13 and 3 and
      the compressive mechanical properties of the tissue/scaffold construct. A low
      permeability design with a spherical pore shape showed a significantly greater
      increase in cartilage matrix formation over 6 weeks in vivo than a high
      permeability design with a cubical pore shape. This increase in cartilage matrix
      synthesis corresponded with increases in mechanical compressive nonlinear elastic
      properties and histological data demonstrating darker red Safranin-O staining.
      There was higher mRNA expression for both cartilage-specific proteins and matrix
      degradation proteins in the high permeability design, resulting in overall less
      sGAG retained in the high permeability scaffold compared with the low
      permeability scaffold. Controlled POC scaffolds with a spherical pore shape and
      low permeability correlated with significantly increased cartilage matrix
      production using primary seeded chondrocytes. These results indicate that the low
      permeability design with a spherical pore shape provided a better
      microenvironment for chondrogenesis than the high permeability design with a
      cubical pore shape. Thus, scaffold architecture and material design may have a
      significant impact on the success of matrix-based clinical cartilage repair
      strategies.

PMID- 20807599
TI  - Deficiency of vitamin A delays bone healing process in association with reduced
      BMP2 expression after drill-hole injury in mice.
AB  - Although it is predicted that vitamin A and its active form, retinoic acid,
      regulate osteoblast lineage, this has not been elucidated in growing mammalians.
      To clarify the direct effect of retinoic acid on bone, we observed the process of
      filling up newly generating bone into a drill-hole of the bone, which is
      understood as membranous ossification, in vitamin A-deficient mice. Mice were
      assigned to three groups: a vitamin A-deficient group (VAD), which was fed a diet
      without vitamin A from the 10th day of gestation to the end of the experiments; a
      vitamin A-deficient-sufficient group (VADS), which was fed a diet without vitamin
      A from the 10th day of gestation to 4 weeks of age; and a vitamin A-sufficient
      group (VAS), which was fed a standard diet to the end of the experiment. In mice
      at 10 weeks of age (day 0), a drill-hole injury was made with a diameter of 1mm
      at the anterior portion of the diaphysis of the bilateral femurs. In VAD,
      retardation in repairing the drill-hole was demonstrated by in vivo micro-CT and
      histomorphometry from day 7 and after surgery. During repair of the bone defect,
      increases of bmp2, dlx5, msx2, col1a1, and osteocalcin mRNA expression were
      suppressed, and runx2-p2 mRNA expression was accelerated in VAD. Implantation of
      BMP2 in the bone defect of VAD normalized the delayed bone healing and mRNA
      expressions. We concluded that vitamin A regulates bmp2 mRNA expression and plays
      a crucial role in osteoblastogenesis and bone formation.

PMID- 20807600
TI  - MR molecular imaging of tumor vasculature and vascular targets.
AB  - Tumor angiogenesis and the ability of cancer cells to induce neovasculature
      continue to be a fascinating area of research. As the delivery network that
      provides substrates and nutrients, as well as chemotherapeutic agents to cancer
      cells, but allows cancer cells to disseminate, the tumor vasculature is richly
      primed with targets and mechanisms that can be exploited for cancer cure or
      control. The spatial and temporal heterogeneity of tumor vasculature, and the
      heterogeneity of response to targeting, make noninvasive imaging essential for
      understanding the mechanisms of tumor angiogenesis, tracking vascular targeting,
      and detecting the efficacy of antiangiogenic therapies. With its noninvasive
      characteristics, exquisite spatial resolution and range of applications, magnetic
      resonance imaging (MRI) techniques have provided a wealth of functional and
      molecular information on tumor vasculature in applications spanning from "bench
      to bedside". The integration of molecular biology and chemistry to design novel
      imaging probes ensures the continued evolution of the molecular capabilities of
      MRI. In this review, we have focused on developments in the characterization of
      tumor vasculature with functional and molecular MRI.

PMID- 20807602
TI  - Targeted systemic gene therapy and molecular imaging of cancer contribution of
      the vascular-targeted AAVP vector.
AB  - Gene therapy and molecular-genetic imaging have faced a major problem: the lack
      of an efficient systemic gene delivery vector. Unquestionably, eukaryotic viruses
      have been the vectors of choice for gene delivery to mammalian cells; however,
      they have had limited success in systemic gene therapy. This is mainly due to
      undesired uptake by the liver and reticuloendothelial system, broad tropism for
      mammalian cells causing toxicity, and their immunogenicity. On the other hand,
      prokaryotic viruses such as bacteriophage (phage) have no tropism for mammalian
      cells, but can be engineered to deliver genes to these cells. However, phage
      based vectors have inherently been considered poor vectors for mammalian cells.
      We have reported a new generation of vascular-targeted systemic hybrid
      prokaryotic-eukaryotic vectors as chimeras between an adeno-associated virus
      (AAV) and targeted bacteriophage (termed AAV/phage; AAVP). In this hybrid vector,
      the targeted bacteriophage serves as a shuttle to deliver the AAV transgene
      cassette inserted in an intergenomic region of the phage DNA genome. As a proof
      of concept, we assessed the in vivo efficacy of vector in animal models of cancer
      by displaying on the phage capsid the cyclic Arg-Gly-Asp (RGD-4C) ligand that
      binds to alphav integrin receptors specifically expressed on the angiogenic blood
      vessels of tumors. The ligand-directed vector was able to specifically deliver
      imaging and therapeutic transgenes to tumors in mice, rats, and dogs while
      sparing the normal organs. This chapter reviews some gene transfer strategies and
      the potential of the vascular-targeted AAVP vector for enhancing the
      effectiveness of existing systemic gene delivery and genetic-imaging
      technologies.

PMID- 20807601
TI  - An integrated approach for the rational design of nanovectors for biomedical
      imaging and therapy.
AB  - The use of nanoparticles for the early detection, cure, and imaging of diseases
      has been proved already to have a colossal potential in different biomedical
      fields, such as oncology and cardiology. A broad spectrum of nanoparticles are
      currently under development, exhibiting differences in (i) size, ranging from few
      tens of nanometers to few microns; (ii) shape, from the classical spherical beads
      to discoidal, hemispherical, cylindrical, and conical; (iii) surface
      functionalization, with a wide range of electrostatic charges and biomolecule
      conjugations. Clearly, the library of nanoparticles generated by combining all
      possible sizes, shapes, and surface physicochemical properties is enormous. With
      such a complex scenario, an integrated approach is here proposed and described
      for the rational design of nanoparticle systems (nanovectors) for the
      intravascular delivery of therapeutic and imaging contrast agents. The proposed
      integrated approach combines multiscale/multiphysics mathematical models with in
      vitro assays and in vivo intravital microscopy (IVM) experiments and aims at
      identifying the optimal combination of size, shape, and surface properties that
      maximize the nanovectors localization within the diseased microvasculature.

PMID- 20807603
TI  - Cationic and tissue-specific protein transduction domains identification,
      characterization, and therapeutic application.
AB  - Protein transduction domains (PTDs) are small peptides able to transverse plasma
      membranes, able to carry proteins, nucleic acid, and viral particles into cells.
      PTDs can be broadly classified into three types; cationic, hydrophobic, and cell
      type specific. The cationic PTDs, comprised of arginines, lysines, and
      ornithines, and hydrophobic PTDs can efficiently transduce a variety of cell
      types in culture and in vivo. The tissue-specific transduction domains,
      identified by screening of peptide display phage libraries for peptides able to
      confer internalization, have more restricted transduction properties. Here we
      provide a review of PTDs, focusing on methods for identifying and characterizing
      both cationic and tissue-specific transduction peptides. In particular, we
      describe the use of screening peptide phage display libraries to identify tissue
      specific transduction peptides.

PMID- 20807604
TI  - GRP78 signaling hub a receptor for targeted tumor therapy.
AB  - Glucose-regulated protein 78 (GRP78) is a potential receptor for targeting
      therapy in cancer and chronic vascular disease due to its overexpression at the
      cell surface in tumor cells and in atherosclerotic lesions. Presence of the GRP78
      autoantibody in cancer patient sera is generally associated with poor prognosis
      since it signals a prosurvival mechanism in response to cellular stress.
      Association of GRP78 with various binding partners involves coordination of
      multiple signaling pathways that result in either cell survival or cell death.
      Binding of activated alpha2-macroglobulin to cell-surface GRP78 activates Akt to
      suppress apoptotic pathways through multiple downstream effectors, and
      concomitantly upregulates NF-kappaBeta and induces the unfolded protein response
      (UPR) so that cell proliferation prevails. Interaction of GRP78 with cell-surface
      T-cadherin promotes endothelial cell survival. Association of oncogenic Cripto
      with GRP78 nullifies TGF-beta superfamily-dependent signaling through Smad2/3 to
      promote cell proliferation. In contrast, association of GRP78 with the
      plasminogen kringle 5 domain or extracellular Par-4 promotes apoptosis.
      Interaction of GRP78 with microplasminogen induces the UPR while association with
      tissue factor inhibits procoagulant activity. The diverse and multiple binding
      proteins of GRP78 and their equally diverse functional outcomes reflect the
      regulatory cellular functions that GRP78 orchestrates. Several GRP78 targeting
      peptides have been isolated from different tumors and they show remarkable tumor
      specificity. Conjugation of GRP78-targeting peptides to an apoptosis-inducing
      peptide suppresses tumor growth in tumor xenografts, thereby demonstrating that
      GRP78 is a viable target by which clinical cancer therapies can be successfully
      developed as well as its potential utility in treating vascular disease.

PMID- 20807605
TI  - On the synergistic effects of ligand-mediated and phage-intrinsic properties
      during in vivo selection.
AB  - Phage display has been used as a powerful tool in the discovery and
      characterization of ligand-receptor complexes that can be utilized for
      therapeutic applications as well as to elucidate disease mechanisms. While the
      basic properties of phage itself have been well described, the behavior of phage
      in an in vivo setting is not as well understood due to the complexity of the
      system. Here, we take a dual approach in describing the biophysical mechanisms
      and properties that contribute to the efficacy of in vivo phage targeting. We
      begin by considering the interaction between phage and target by applying a
      kinetic model of ligand-receptor complexation and internalization. The
      multivalent display of peptides on the pIII capsid of phage is also discussed as
      an augmenting factor in the binding affinity of phage-displayed peptides to
      cellular targets accessible in a microenvironment of interest. Lastly, we examine
      the physical properties of the total phage particle that facilitate improved
      delivery and targeting in vivo compared to free peptides.

PMID- 20807606
TI  - Strategies for targeting tumors and tumor vasculature for cancer therapy.
AB  - Effective cancer therapy remains a challenge despite recent advances in the
      identification of novel targets. A major limitation of most chemotherapeutic
      drugs is their systemic toxicity and the efficacy of cancer treatments is, by and
      large, determined by the ability to balance their benefits against their
      toxicity. Targeted treatments for cancer, especially those that target the tumor
      vasculature, have provided promising antitumor results with minimal systemic
      toxicity. To date significant progress has been made in developing a variety of
      delivery systems to target cancer and its vasculature ranging from isolated limb
      and organ perfusion to tumor targeted biological and nonbiological vectors.

PMID- 20807607
TI  - Genetics and genetic testing in kidney disease: introduction.

PMID- 20807608
TI  - Diagnosis of autosomal-dominant polycystic kidney disease: an integrated
      approach.
AB  - Autosomal-dominant polycystic kidney disease (ADPKD) is the most common Mendelian
      disorder of the kidney and accounts for approximately 5% of end-stage renal
      disease in developed countries. It is characterized by focal and sporadic
      development of renal cysts that increase in number and size with age. Mutations
      of 2 genes (ie, PKD1 and PKD2) account for most of the cases. Although the
      clinical manifestations of both gene types overlap completely, PKD1 is associated
      with more severe disease than PKD2, with bigger kidneys and earlier onset of end
      stage renal disease. In general, the diagnosis of ADPKD is commonly made by renal
      ultrasonography. Age-dependent ultrasound criteria have been established for both
      diagnosis and disease exclusion in subjects at risk of PKD1. However, the utility
      of these criteria in the clinic setting is unclear because their performance
      characteristics have not been defined for the milder PKD2 and the gene type for
      most test subjects is unknown. Recently, highly predictive ultrasound diagnostic
      criteria have been derived for at-risk subjects of unknown gene type. In
      addition, molecular genetic testing is now available for the diagnosis of ADPKD,
      especially in subjects with equivocal imaging results, with a negative or
      indeterminate family history, or in younger at-risk individuals with a negative
      ultrasound study being evaluated as potential living-related kidney donor. Here,
      we review the clinical utilities and limitations of these imaging- and molecular
      based diagnostic tests, and outline our approach for the evaluation of
      individuals suspected to have ADPKD.

PMID- 20807609
TI  - Hereditary interstitial kidney disease.
AB  - Autosomal-dominant interstitial kidney disease is characterized by slow
      progression of chronic kidney disease in patients with bland urinary sediment and
      no or low-grade proteinuria. There are at least three subtypes. Patients with
      mutations in the UMOD gene encoding uromodulin suffer from precocious gout in
      addition to chronic kidney failure. Diagnosis can be achieved through genetic
      analysis of the UMOD gene. Patients with mutations in the REN gene encoding renin
      suffer from anemia in childhood, hyperuricemia, mild hyperkalemia, and
      progressive kidney disease. Genetic analysis of the REN gene can be performed to
      diagnose affected individuals. There is a third form of inherited interstitial
      kidney disease for which the cause has not been found. These individuals suffer
      from chronic kidney disease with no other identified clinical signs. Linkage to
      chromosome 1 has been identified in a number of these families. Proper diagnosis
      is valuable not only to the affected individual but also to the entire family and
      can facilitate treatment, transplantation, and research efforts.

PMID- 20807610
TI  - Congenital anomalies of kidney and urinary tract.
AB  - Congenital anomalies of the kidney and urinary tract anatomy (CAKUT) are common
      in children and represent approximately 30% of all prenatally diagnosed
      malformations. CAKUT is phenotypically variable and can affect the kidney(s)
      alone and/or the lower urinary tract. The spectrum includes more common anomalies
      such as vesicoureteral reflux and, rarely, more severe malformations such as
      bilateral renal agenesis. In young children, congenital anomalies are the leading
      cause of kidney failure and for kidney transplantation or dialysis. CAKUT can
      also lead to significant renal problems in adulthood and may present itself with
      hypertension and/or proteinuria. Congenital renal anomalies can be sporadic or
      familial, syndromic (also affecting nonrenal or non-urinary tract tissues), or
      nonsyndromic. Genetic causes have been identified for the syndromic forms and
      have shed some light into the molecular mechanisms of kidney development in human
      beings. The genetic causes for the more common nonsyndromic forms of CAKUT are
      unknown. The role of prenatal interventions and postnatal therapies as well as
      the benefits of screening affected individuals and their family members are not
      clear.

PMID- 20807611
TI  - Clinical evaluation of Mendelian hypertensive and hypotensive disorders.
AB  - The elucidation of the molecular bases of a number of Mendelian disorders with
      primary effect on blood pressure has enabled improved recognition and diagnosis
      of these rare disorders. Prompt diagnosis can be a vital and perhaps lifesaving
      component of care for patients who present with unexplained and perhaps familial
      hypertension or hypotension. Formal diagnosis of these disorders may require DNA
      sequencing, which often is not immediately available. Here, clinical clues
      enabling diagnosis of these various disorders are reviewed.

PMID- 20807612
TI  - Genetics and genetic testing in hemolytic uremic syndrome/thrombotic
      thrombocytopenic purpura.
AB  - The hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP)
      are rare diseases that manifest with thrombocytopenia and microangiopathic
      hemolytic anemia accompanied by renal and neurologic dysfunction. Most childhood
      cases of HUS are caused by Shiga-toxin-producing bacteria and have a good
      prognosis. The other form, atypical HUS (aHUS), accounts for 10% of cases.
      Prognosis of aHUS and TTP has changed over time from fatal disorders to 60% to
      80% survival in the plasma therapy era. In the past 10 years the molecular bases
      of aHUS and TTP have been discovered that mostly lead to uncontrolled activation
      of the complement system in aHUS and to abnormal von Willebrand factor processing
      in TTP. Identification of the underlying abnormality in an individual patient can
      provide prognostically significant information in predicting long-term outcome,
      response to therapies, and transplant outcome. It also paves the way for the use
      of specific new therapies in the near future.

PMID- 20807614
TI  - Gene polymorphisms in renal transplantation.
AB  - A vast majority of gene polymorphism studies in renal transplantation focus on
      short-term outcomes such as acute rejection. The main purpose of this article is
      to review the literature available and studies that have examined the association
      between the gene polymorphisms and long-term renal allograft functions. In this
      review, we focus on commonly reported genes in the renin angiotensin system,
      transforming growth factor-beta gene, and metalloproteinases on the incidence and
      progression of chronic renal allograft dysfunction.

PMID- 20807615
TI  - Translating research discoveries into clinical tests.
AB  - In the past decade, mutations in many genes have been discovered to underlie the
      myriad of inherited renal and other genetic diseases. Once these genes are
      identified as etiologic in a disease, the development of a clinical test becomes
      possible. However, clinical tests are not yet available for all identified
      disease genes. Why is that? This article discusses the many factors that
      influence making such a test available and describe the common challenges that
      are encountered during translation of a test into clinical use.

PMID- 20807613
TI  - MYH9 genetic variants associated with glomerular disease: what is the role for
      genetic testing?
AB  - Genetic variation in MYH9, encoding nonmuscle myosin IIA heavy chain, has been
      associated recently with increased risk for kidney disease. Previously, MYH9
      missense mutations have been shown to cause the autosomal-dominant MYH9 (ADM9)
      spectrum, characterized by large platelets, leukocyte Dohle bodies, and,
      variably, sensorineural deafness, cataracts, and glomerulopathy. Genetic testing
      is indicated for familial and sporadic cases that fit this spectrum. By contrast,
      the MYH9 kidney risk variant is characterized by multiple intronic single
      nucleotide polymorphisms, but the causative variant has not been identified.
      Disease associations include human immunodeficiency virus-associated collapsing
      glomerulopathy, focal segmental glomerulosclerosis, hypertension-attributed end
      stage kidney disease, and diabetes-attributed end-stage kidney disease. One
      plausible hypothesis is that the MYH9 kidney risk variant confers a fragile
      podocyte phenotype. In the case of hypertension-attributed kidney disease, it
      remains unclear if the hypertension is a contributing cause or a consequence of
      glomerular injury. The MYH9 kidney risk variant is strikingly more common among
      individuals of African descent, but only some will develop clinical kidney
      disease in their lifetime. Thus, it is likely that additional genes and/or
      environmental factors interact with the MYH9 kidney risk variant to trigger
      glomerular injury. A preliminary genetic risk stratification scheme, using two
      single nucleotide polymorphisms, may estimate lifetime risk for kidney disease.
      Nevertheless, at present, no role has been established for genetic testing as
      part of personalized medicine, but testing should be considered in clinical
      studies of glomerular diseases among populations of African descent. Such studies
      will address critical questions pertaining to MYH9-associated kidney disease,
      including mechanism, course, and response to therapy.

PMID- 20807616
TI  - Principles of genetic testing and genetic counseling for renal clinicians.
AB  - The advancement of genetic information and increased access to genetic testing
      options requires renal clinicians to expand their working knowledge of genetics
      and translate this information in a way that is meaningful to their patients. It
      is helpful to distinguish between the three types of genetic testing: clinical
      genetic testing, research genetic testing, and direct to consumer testing, and to
      communicate these differences to patients interested in these options. Although
      clinicians may not have the time to stage an entire genetic counseling session
      with each patient, the following scenarios offer tools and techniques from
      genetic counseling that can be used to facilitate the genetic testing process,
      foster client decision making, and to identify patients who may benefit from
      referral to a genetic counselor for additional support.

PMID- 20807617
TI  - Sonographic follow-up of patients with carpal tunnel syndrome undergoing surgical
      or nonsurgical treatment: prospective cohort study.
AB  - PURPOSE: To compare changes in the largest cross-sectional area (CSA) of the
      median nerve in wrists undergoing surgical decompression with changes in wrists
      undergoing non-surgical treatment of carpal tunnel syndrome (CTS). METHODS: This
      study was a prospective cohort study in 55 consecutive patients with 78 wrists
      with established CTS, including 60 wrists treated with surgical decompression and
      18 wrists with non-surgical treatment. A sonographic examination was scheduled
      before and 4 months after initiation of treatment. We compared changes in CSA of
      the median nerve between wrists with surgical treatment and wrists with non
      surgical treatment using linear regression models. RESULTS: Decreases in CSA of
      the median nerve were more pronounced in wrists with CTS release than in wrists
      undergoing nonsurgical treatment (difference in means, 1.0 mm(2); 95% confidence
      interval, 0.3-1.8 mm(2)). Results were robust to the adjustment for age, gender,
      and neurological severity at baseline. Among wrists with CTS release, those with
      postoperative CSA of 10 mm(2) or less tended to have better clinical outcomes
      than those with postoperative CSA of greater than 10 mm(2) (p=.055).
      Postoperative sonographic workup in the 3 patients with unfavorable outcome or
      recurrence identified likely causes for treatment failure in 2 patients.
      CONCLUSIONS: In this observational study, surgical decompression was associated
      with a greater decrease in median nerve CSA than was nonsurgical treatment.
      Smaller postoperative CSAs may be associated with better clinical outcomes.
      Additional randomized trials are necessary to determine the optimal treatment
      strategy in different subgroups of patients with CTS. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic III.

PMID- 20807618
TI  - Muscle-in-vein nerve guide for secondary reconstruction in digital nerve lesions.
AB  - PURPOSE: Although vein conduits filled with fresh skeletal muscle have been used
      to bridge nerve defects both experimentally and clinically with good results,
      this approach has never been considered a valuable tool for reconstruction of
      nerve defects, and the technique has been abandoned. The purpose of this study
      was to evaluate the application of muscle-in-vein conduits for secondary digital
      nerves reconstruction, with particular emphasis on the surgical technique and
      results. METHODS: We present a retrospectively selected consecutive series of 21
      digital nerve defects in 17 patients who were treated with vein conduits filled
      with fresh skeletal muscle for secondary nerve reconstruction. After a minimum
      follow-up of 18 months, all patients were studied with static and moving 2-point
      discrimination, Semmes-Weinstein monofilament testing, Visual Analog Scale, and
      Disabilities of the Arm, Shoulder, and Hand questionnaire. Outcome data were
      stratified according to the American Society for Surgery of the Hand guidelines,
      the modified Highet and Sander's criteria, and the Logic Tree. RESULTS: The
      average nerve gap bridged with the muscle-in-vein conduit was 2.2 cm (range, 1
      3.5 cm). We classified 14 of 22 reconstructed nerves as excellent or good
      according to American Society for Surgery of the Hand guidelines, whereas 17 were
      between S4 and S3 using modified Highet and Sander's criteria. The Logic Tree
      yielded results between S4 and S3 in 14 of 21 reconstructed nerves. The average
      Disabilities of the Arm, Shoulder, and Hand survey scores were 22.5 for the
      disability/symptoms module and 21.4 and 17 for the sports/music and work
      subcomponents, respectively. CONCLUSIONS: Use of muscle-in-vein conduits should
      be considered and promoted for sensory nerve reconstruction for a number of
      reasons: the encouraging results with the technique; the abundant availability of
      both donor tissues; the flexibility of the conduit resulting from the combination
      of muscle and vein; the simplicity with which tubes can be fashioned;
      immunological compatibility; and the absence of adjunctive costs. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 20807619
TI  - Long thoracic nerve neurotization for restoration of shoulder function in C5-7
      brachial plexus preganglionic injuries: case report.
AB  - C5-7 brachial plexus preganglionic injuries are usually associated with complete
      paralysis of the long thoracic nerve. This makes it difficult to provide
      satisfactory shoulder function by neurotizing only the suprascapular nerve,
      compared with C5 and C6 preganglionic injuries, in which the long thoracic nerve
      is spared. We present a case report of a 21-year-old man who sustained a C5-7
      brachial plexus preganglionic injury and obtained excellent shoulder function by
      intercostal nerve transfer to the long thoracic nerve in addition to
      neurotization of the suprascapular nerve. Our report emphasizes the importance of
      restoring the activity of the long thoracic nerve.

PMID- 20807620
TI  - Ulnar nerve to musculocutaneous nerve transfer in an ulnar ray-deficient infant
      with brachial plexus birth palsy: case report.
AB  - In Oberlin's nerve transfer, a fascicle of the ulnar nerve is sutured end-to-end
      to the branch of musculocutaneous nerve to the biceps muscle in the arm. This
      transfer is commonly used in adult traumatic C5-C6 avulsion injuries of the
      brachial plexus. We report the successful use of Oberlin nerve transfer in an
      ulnar ray-deficient infant with brachial plexus birth palsy.

PMID- 20807621
TI  - Age- and site-related bone mineral densities in Korean women with a distal radius
      fracture compared with the reference Korean female population.
AB  - PURPOSE: To assess age- and site-related bone mineral density (BMD) values in
      Korean female patients with a distal radius fracture, and to compare them with
      those of the community-based general Korean female population. METHODS: For this
      study, we recruited 54 consecutive Korean women, 50 to 79 years of age, with a
      distal radius fracture caused by minor trauma. We performed dual-energy x-ray
      absorptiometry scans at central sites: the lumbar spine, femoral neck,
      trochanter, and Ward's triangle, which is a triangular area within the femoral
      neck. Age- and site-related BMDs were assessed and compared with those of
      population-based reference data for Korean women. RESULTS: The overall prevalence
      (defined as meeting the osteoporosis criteria in at least one of the earlier
      described measurement areas) of osteoporosis in patients with a distal radius
      fracture was 57%. The site-related prevalence was 54% at Ward's triangle, 43% at
      the lumbar spine, 32% at the femoral neck, and 26% at the trochanter, and these
      values were individually statistically significantly higher than those of the
      general Korean female population except for the lumbar spine. In patients 50 to
      59 and 70 to 79 years of age, patients' mean BMD values at the hip were
      statistically significantly lower than those of the reference female population
      of corresponding age groups, but the hip BMD differences were not statistically
      significant in patients 60 to 69 years of age. There were no statistically
      significant BMD differences measured at the lumbar spine in any age group.
      CONCLUSIONS: Korean female patients with a distal radius fracture, 50 to 59 and
      70 to 79 years of age, had lower BMDs at the hip than the reference Korean female
      population. However, no statistically significant BMD differences were found in
      those 60 to 69 years of age. Low BMD may have a greater impact on distal radius
      fracture in women younger than 60 years of age or over 70 years of age.
      Considering the young onset of bone loss, patients younger than 60 years of age
      with a distal radius fracture are a good target group for secondary prevention of
      osteoporosis.

PMID- 20807622
TI  - Motion deficit of the thumb in CMC joint arthritis.
AB  - PURPOSE: Idiopathic osteoarthritis (OA) of the thumb carpometacarpal (CMC) joint
      is a common disabling disease that often causes pain and motion loss. The aims of
      this study were to characterize the multidimensional motion capability of the
      thumb CMC joint in a group with severe CMC OA and to compare it with a control
      group. METHODS: We included 15 subjects with stage III/IV CMC OA according to the
      Eaton/Littler classification, and 15 control subjects. A motion analysis system
      using surface markers was employed to quantify the maximum boundary of the thumb
      circumduction envelope during repetitive thumb movements. We measured the area
      enclosed by the angular circumduction envelope and the ranges of motion (ROM) in
      multiple directions for the thumb CMC joint. RESULTS: Thumb osteoarthritis of the
      CMC joint stage III/IV resulted in a significantly smaller ROM in
      flexion/extension (45 degrees +/- 11 degrees for the CMC OA group, 59 degrees +/-
      10 degrees for the controls), abduction-adduction (37 degrees +/- 6 degrees for
      the CMC OA group, 63 degrees +/- 13 degrees for the controls), and pronation
      supination (49 degrees +/- 10 degrees for the CMC OA group, 62 degrees +/- 11
      degrees for the controls) (p < .01). When analyzing the motion directions in
      flexion-extension and abduction-adduction separately, there was only a loss of
      extension and adduction (p < .01). CONCLUSIONS: Severe stages of thumb CMC OA
      cause an asymmetrical motion deficit with decreased ROM in extension and
      adduction, leading to decreased capability of counteropposition.

PMID- 20807623
TI  - Combined dislocation of the trapezoid and finger carpometacarpal joints-the
      steering wheel injury: case report.
AB  - Two cases of combined dorsal trapezoid dislocation and multiple finger
      carpometacarpal joint dislocations are described. In both cases, a common
      mechanism involved a head-on motor vehicle collision while the subjects held
      tightly to the steering wheel. The patients were treated with open reduction and
      pinning, with good short-term results.

PMID- 20807624
TI  - Tissue engineering of flexor tendons: the effect of a tissue bioreactor on
      adipoderived stem cell-seeded and fibroblast-seeded tendon constructs.
AB  - PURPOSE: Tissue-engineered flexor tendons could eventually be used for
      reconstruction of large tendon defects. The goal of this project was to examine
      the effect of a tissue bioreactor on the biomechanical properties of tendon
      constructs seeded with adipoderived stem cells (ASCs) and fibroblasts (Fs).
      METHODS: Rabbit rear paw flexor tendons were acellularized and seeded with ASCs
      or Fs. A custom bioreactor applied a cyclic mechanical load of 1.25 N at 1
      cycle/minute for 5 days onto the tendon constructs. Three additional groups were
      used as controls: fresh tendons and tendons reseeded with either ASCs or Fs that
      were not exposed to the bioreactor treatment and were left in stationary
      incubation for 5 days. We compared the ultimate tensile stress (UTS) and elastic
      modulus (EM) of bioreactor-treated tendons with the unloaded control tendons and
      fresh tendons. Comparison across groups was assessed using one-way analysis of
      variance with the significance level set at p<.05. Pairwise comparison between
      the samples was determined by using the Tukey test. RESULTS: The UTS and EM
      values of bioreactor-treated tendons that were exposed to cyclic load were
      significantly higher than those of unloaded control tendons. Acellularized tendon
      constructs that were reseeded with ASCs and exposed to a cyclic load had a UTS of
      66.76 MPa and an EM of 906.68 MPa; their unloaded equivalents had a UTS of 47.90
      MPa and an EM of 715.57 MPa. Similar trends were found in the fibroblast-seeded
      tendon constructs that were exposed to the bioreactor treatment. The bioreactor
      treated tendons approached the UTS and EM values of fresh tendons.
      Histologically, we found that cells reoriented themselves parallel to the
      direction of strain in response to cyclic strain. CONCLUSIONS: The application of
      cyclic strain on seeded tendon constructs that were treated with the bioreactor
      helped achieve a UTS and an EM comparable with those of fresh tendons. Bioreactor
      pretreatment and alternative cell lines, such as ASCs and Fs, might therefore
      contribute to the in vitro production of strong tendon material.

PMID- 20807625
TI  - Predictive value of magnetic resonance imaging in determining presence of
      residual disease after marginal excision of unsuspected soft tissue sarcomas of
      the hand.
AB  - PURPOSE: Diagnosis of a soft tissue sarcoma of the hand is at times made only in
      retrospect after marginal excision of a presumed benign soft tissue mass.
      Magnetic resonance imaging (MRI) helps determine the presence of residual disease
      and the extent of contamination caused by marginal excision of unsuspected soft
      tissue sarcomas and assists in the planning of definitive treatment with surgery
      and radiotherapy when required. We sought to determine the accuracy of MRI in
      detecting residual sarcoma after marginal excision. METHODS: We retrospectively
      studied case records and imaging studies for all patients with soft tissue
      sarcomas of the hand evaluated and treated at our institution from 1996 to 2005.
      We included in this study 33 patients who underwent definitive surgery at our
      center after prior marginal excision. MRI scans done before definitive wide
      resection were classified as positive or negative for residual tumor. A
      musculoskeletal radiologist, blinded to the sarcoma type, findings on
      histopathology, and surgery, reviewed 19 scans to see whether the accuracy could
      be improved. RESULTS: There were 8 epithelioid sarcomas, 6 synovial sarcomas, 4
      malignant fibrous histiocytomas, 2 leiomyosarcomas, 2 liposarcomas, 2
      myxofibrosarcomas, and one each of 9 other diagnoses. A total of 11 were low
      grade and 22 were high-grade tumors, with 4 superficial and 29 deep tumors.
      Pathology examination after definitive wide resection or partial hand amputation
      showed that 15 patients had residual tumor, 9 gross and 6 microscopic. The
      sensitivity of MRI in detecting residual soft tissue sarcoma of the hand was 60%,
      specificity was 78%, positive predictive value was 69%, and negative predictive
      value was 70%. The sensitivity of MRI in detecting gross residual soft tissue
      sarcoma of the hand was 89%, specificity was 79%, positive predictive value was
      62%, and negative predictive value was 95%. Even when an experienced
      musculoskeletal radiologist reassessed 19 MRI scans, the accuracy did not
      improve. CONCLUSIONS: Magnetic resonance imaging does not reliably detect
      residual gross or microscopic soft tissue sarcoma after marginal excision of
      unsuspected soft tissue sarcomas of the hand, with residual tumor not readily
      distinguished from postoperative change. The absence of disease on MRI should not
      be used as the sole criterion in determining whether a repeat resection should be
      performed. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic III.

PMID- 20807626
TI  - Standardized protocol for artery-only fingertip replantation.
AB  - PURPOSE: Artery-only fingertip replantation can be reliable if low-resistance
      flow through the replant is maintained until venous outflow is restored
      naturally. Injuring the tip of the replant to promote ongoing bleeding augmented
      with anticoagulation usually accomplishes this; however, such management results
      in prolonged hospitalization. In this study, we analyzed the outcomes of artery
      only fingertip replantation using a standardized postoperative protocol
      consisting of dextran-40, heparin, and leech therapy. METHODS: Between 2001 and
      2008, we performed 19 artery-only fingertip replants for 17 patients. All
      patients had the replanted nail plate removed and received intravenous dextran
      40, heparin, and aspirin to promote fingertip bleeding and vascular outflow.
      Anticoagulation was titrated to promote a controlled bleed until physiologic
      venous outflow was restored by neovascularization. We used medicinal leeches and
      mechanical heparin scrubbing for acute decongestion. By postoperative day 6,
      bleeding was no longer promoted. We initiated fluorescent dye perfusion studies
      to assess circulatory competence and direct further anticoagulant intervention if
      necessary. The absence of bleeding associated with an initial rise followed by an
      appropriate fall in fluorescent dye concentration would trigger a weaning of
      anticoagulation. RESULTS: All of the 19 replants survived. The average length of
      hospital stay was 9 days (range, 7-17 d). Eleven patients received blood
      transfusions. The average transfusion was 1.8 units (range, 0-9 units). All
      patients were happy with the decision to replant, and the cosmetic result.
      CONCLUSIONS: A protocol that promotes temporary, controlled bleeding from the
      fingertip is protective of artery-only replants distal to the distal
      interphalangeal joint until physiologic venous outflow is restored. The protocol
      described is both safe and reliable. The patient should be informed that such
      replant attempts may result in the need for transfusions and extended hospital
      stays, factors that can help the physician and patient decide whether to proceed
      with replantation. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 20807628
TI  - Congenital dorsally curving deformity of the distal phalanx of the little finger:
      case report.
AB  - A deformity of the distal phalanx of the little finger with a curvature in the
      dorsal direction, referred to as a reverse Kirner's deformity, is extremely rare.
      We present a case of such a deformity found in a 6-year-old girl. A successful
      result was obtained after double corrective osteotomy of the distal phalanx at 12
      years of age.

PMID- 20807627
TI  - Radial longitudinal deficiencies with hypoplastic/absent thumbs and cutaneous
      syndactyly of the most radial digits.
AB  - PURPOSE: To describe radial longitudinal deficiency with hypoplastic or absent
      thumb and cutaneous syndactyly between the most radial digits. In addition, to
      discuss the clinical relevance and unique treatment decisions involved in
      optimizing functional outcomes in these patients. METHODS: A total of 163
      extremities of 122 patients with radial longitudinal deficiencies were reviewed.
      We reviewed radiographs and clinical images that were available, with most radial
      hypoplastic digit and cutaneous syndactyly to the adjacent finger. RESULTS: There
      were 7 hands with this type of deformity. Four cases had a hypoplastic thumb
      associated with cutaneous syndactyly between the thumb and index finger. Three
      cases had a deformity in which the thumb was absent and the hypoplastic index
      finger was syndactylized to the long finger. Proximal and distal radioulnar
      synostoses were associated with these deformities in 3 patients. CONCLUSIONS:
      Because the most radial digit is severely hypoplastic in this type of deformity,
      pollicization is usually indicated. However, the pollicization procedure must be
      modified due to associated syndactyly with different degrees of hypoplasia or
      absence of the intrinsic muscles. This type of deformity should be distinguished
      from hypoplastic thumb without syndactyly. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 20807629
TI  - Interference screw failure in distal biceps endobutton repair: case report.
AB  - Endobutton (Arthrex, Naples, FL) fixation of distal biceps rupture with
      interference screw fixation provides for a secure repair, allowing for early
      motion. We present a case in which Endobutton fixation failed with a loose
      interference screw, rendering the distal biceps attachment incompetent. Revision
      surgery with an extensile approach, mobilization of the biceps, and repeat
      Endobutton fixation at a more distal site provided a secure fixation with an
      excellent clinical outcome. An understanding of the mechanism of failure might
      allow surgeons to perform this procedure with a lower incidence of complications.

PMID- 20807630
TI  - Nerve tumors.

PMID- 20807632
TI  - A hand surgeon's further experience with thoracic outlet compression syndrome.
AB  - Because hand surgeons frequently see patients with arm and hand pain, numbness,
      and tingling, it is important for them to recognize the possibility of the
      presence of thoracic outlet compression syndrome (TOCS). Approximately 40% to 50%
      of patients with this condition have associated peripheral nerve compression
      symptoms. Only about 10% of patients with suspected TOCS might show some
      objective evidence during physical examination and other examination modalities.
      For this reason, TOCS is one of the most overlooked, misdiagnosed, and underrated
      conditions. During the past 20 years (1989-2009) our surgical experience with
      combined-approach surgery for TOCS, involving transaxillary first rib resection
      followed by immediate transcervical anterior and middle scalenectomy, has been
      gratifying. During this period, more than 750 patients had this combined
      procedure. Between the end of 1989 and 2002 (13 years), 532 patients (many of
      whom were from out of state) had this kind of intervention. At the end of 2002,
      we surveyed our patients for the outcome of their surgery. Unfortunately, we were
      able to locate only 358 patients, and only 102 patients returned a mailed
      questionnaire. About 95 patients reported improvement of their symptoms. Since
      the beginning of 2003, more than 230 patients have had the same procedure. It is
      our impression that the outcome of the surgery in this last group of patients is
      at least as good as (if not better than) the earlier reported outcome in the
      first group of patients. The combined surgical approach to TOCS with
      transaxillary first rib resection and transcervical scalenectomy is the most
      complete procedure for total decompression of the thoracic outlet, with a much
      better rate of improvement of symptoms and a lower rate of recurrences. The
      surgical techniques of these two procedures are described.

PMID- 20807631
TI  - Zone II combined flexor digitorum superficialis and flexor digitorum profundus
      repair distal to the A2 pulley.

PMID- 20807633
TI  - Vascular insufficiency of the upper extremity.
AB  - Vascular insufficiency of the upper extremity can be due to acute vascular
      injury, chronic vasospastic disease, and occlusive disease. Its treatment
      requires a thorough understanding of the vascular anatomy of the upper extremity,
      diagnostic modalities, and medical and surgical management options. Promising
      advances continue to be made in surgical treatment and medical therapy.

PMID- 20807634
TI  - Ethics and professionalism for hand surgeons.

PMID- 20807635
TI  - Cubital tunnel syndrome: ulnar nerve subluxation.

PMID- 20807637
TI  - Glycosaminoglycans in development, health and disease. Preface.

PMID- 20807638
TI  - Glycosaminoglycan (GAG) biosynthesis and GAG-binding proteins.
AB  - Two major types of glycosaminoglycan (GAG) polysaccharides, heparan sulfate and
      chondroitin sulfate, are polymerized and modified by enzymes that are encoded by
      more than 40 genes in animal cells. Because of the expression repertoire of the
      GAG assembly and modification enzymes, each heparan sulfate and chondroitin
      sulfate chain has a sulfation pattern, chain length, and fine structure that is
      potentially unique to each animal cell. GAGs interact with hundreds of proteins.
      Such interactions protect growth factors, chemokines, and cytokines against
      proteolysis. GAGs catalyze protease (such as thrombin) inhibition by serpins.
      GAGs regulate multiple signaling pathways including, but not limited to,
      fibroblast growth factor (FGF)/FGFR, hepatocyte growth factor (HGF)/c-Met, glial
      cell line-derived neurotrophic factor (GDNF)/c-Ret/GFRalpha1, vascular
      endothelial growth factor (VEGF)/VEGFR, platelet derived growth factor
      (PDGF)/PDGFR, BAFF/TACI, Indian hedgehog, Wnt, and BMP signaling pathways,where
      genetic studies have revealed an absolute requirement for GAGs in these pathways.
      Most importantly, protein/GAG aggregates induce thrombin generation and immune
      system upregulation by activating the contact system. Abnormal protein/GAG
      aggregates are associated with a variety of devastating human diseases including,
      but not limited to, Alzheimer's, diabetes, prion or transmissible spongiform
      encephalopathies, Lupus, heparin-induced thrombocytopenia/thrombosis, and
      different kinds of cancers. Therefore, GAGs are essential components of modern
      molecular biology and human physiology. Understanding GAG structure and function
      at molecular level with regard to development and health represents a unique
      opportunity in combating different kinds of human diseases.

PMID- 20807639
TI  - Mice deficient in glucuronyltransferase-I.
AB  - Chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS), and
      heparin (Hep) are a class of glycosaminoglycans (GAGs) that are distributed on
      the surface of virtually all cells and in the extracellular matrices. CS/DS and
      HS/Hep chains share a common carbohydrate-protein linkage region structure,
      GlcAbeta1-3Galbeta1-3Galbeta1-4Xylbeta1-O-Ser. Glucuronyl transfer to the Gal
      residue, the final biosynthetic step in the common linkage region, is catalyzed
      by a key enzyme, beta1,3-glucuronyltransferase, which is termed
      glucuronyltransferase I (GlcAT-I). As it has been reported that the expression
      level of GlcAT-I correlates well with the amount of GAGs, GlcAT-I is thought to
      regulate the expression of GAGs. In fact, a defect in the squashed vulva 8 (sqv
      8) gene which encodes GlcAT-I in Caenorhabditis elegans eliminates the expression
      of GAGs and the mutant worms show not only a perturbation in vulval invagination
      but also a defect in the cytokinesis in fertilized eggs, resulting in alternating
      cell division and cell fusion. Here, we summarize the recent knowledge on the
      roles of GlcAT-I in mammalian GAG biosynthesis and embryonic cell division using
      GlcAT-I knock-out mice.

PMID- 20807640
TI  - Mice deficient in heparan sulfate N-deacetylase/N-sulfotransferase 1.
AB  - Ndsts (N-deacetylase/N-sulfotransferases) are enzymes responsible for N-sulfation
      during heparan sulfate (HS) and heparin biosynthesis. In this review, basic
      features of the Ndst1 enzyme are covered and a brief description of HS
      biosynthesis and its regulation is presented. Effects of Ndst1 deficiency on
      embryonic development are described. These include immature lungs, craniofacial
      dysplasia and eye developmental defects, branching defect during lacrimal gland
      development, delayed mineralization of the skeleton, and reduced pericyte
      recruitment during vascular development. A brief account of the effects of Ndst1
      deficiency in selective cell types in adult mice is also given.

PMID- 20807641
TI  - Glucuronyl C5-epimerase an enzyme converting glucuronic acid to iduronic acid in
      heparan sulfate/heparin biosynthesis.
AB  - The glucuronyl C5 epimerase (HSepi) is one of the modification enzymes involved
      in biosynthesis of heparan sulfate (HS) and heparin, catalyzing the epimerization
      of D-glucuronic acid (GlcA) to L-iduronic acid (IdoA) at polymer level. IdoA is
      critical for HS and heparin to interact with protein ligands, because of its
      flexible conformation. Although the enzyme recognizes both GlcA and IdoA as
      substrates catalyzing a reversible reaction of the hexuronic acids in vitro, the
      reaction appears irreversible in vivo. Targeted interruption of the gene, Glce,
      in mice resulted in neonatal lethality accompanied with kidney agenesis,
      premature lung, and skeletal malformations, demonstrating that the single gene
      coded enzyme is essential for animal development. Elimination of the enzyme
      resulted in abnormal HS and heparin structure that completely lacks IdoA
      residues. Loss of 2-O-sulfation due to lacking IdoA in HS chains appears
      compensated by increased N- and O-sulfation of the glucosamine residues.
      Recombinant HSepi is used to generate HS/heparin related compounds having
      potential to be used for therapeutic purposes.

PMID- 20807642
TI  - Mice deficient in heparan sulfate 6-O-sulfotransferase-1.
AB  - Heparan sulfate chains are initially synthesized on core proteins as linear
      polysaccharides composed of glucuronic acid-N-acetylglucosamine repeating units
      and subjected to marked structural modification by sulfation at various places
      and epimerization of hexuronic acid residues (C5-epimerase) at the Golgi lumen
      and further by 6-O-desulfation at the cell surface, which generates their
      characteristic divergent fine structures. This chapter focuses on the biological
      and physiological functions of 6-O-sulfation in HS and the characterization of
      the enzymes catalyzing 6-O-sulfation (HS6ST). HS6STs in mammals such as humans
      and mice comprise of three isoforms (HS6ST-1, -2, and -3) and one alternatively
      spliced form of HS6ST-2 (HS6ST-2S). Each of these isoforms has distinct substrate
      preferences, albeit overlapping each other. These HS6ST isoforms are expressed in
      a spatiotemporally regulated manner in most organs. HS6ST-1-deficient mice are
      lethal mostly at later embryonic stages and exhibit abnormal angiogenesis in
      labyrinthine zone of placenta and aberrant lung morphology similar to pulmonary
      emphysema. These knockout mice also exhibit retinal axon guidance abnormality at
      the optic chiasm. Other HS6ST-deficient animals reveal various malformations in
      muscle development and branching morphology of the caudal vein of zebrafish, in
      tracheal formation of Drosophila, and in axon guidance of ventral nerve cord
      interneurons of Caenorhabditis elegans. Mouse embryonic fibroblasts prepared from
      HS6ST-1/HS6ST-2 double knockout mice did produce HS lacking 6-O-sulfation and
      responded differently to various FGFs dependent signaling.

PMID- 20807643
TI  - The roles of chondroitin-4-sulfotransferase-1 in development and disease.
AB  - The glycosaminoglycan chondroitin sulfate (CS) consists of long linear chains of
      repeating disaccharide units, which are covalently attached to core proteins to
      form CS-proteoglycans. These molecules have been shown to fulfill important
      biological functions in development, disease, and signaling. Biosynthesis of CS
      takes place in the Golgi apparatus. Concomitant to chondroitin chain elongation,
      sulfation of specific carbon residues by chondroitin sulfotransferase enzymes
      takes place. The sulfation balance and pattern of CS on specific carbon residues
      are tightly regulated during development, injury, and disease, with the temporal
      and spatial expression of chondroitin sulfotransferase genes believed to be a
      crucial determinant of this fine balance of chondroitin sulfation. Chondroitin-4
      sulfotransferase-1 (C4ST-1)/carbohydrate sulfotransferase 11 (CHST11) is one of
      the enzymes involved in the sulfation of chondroitin by catalyzing the transfer
      of sulfate groups from a sulfate donor to the carbon-4 position of the N
      acetylgalactosamine sugar of the repeating disaccharide units. Here, I summarize
      the significant recent advances in our understanding of the roles of C4ST-1 in
      vertebrate development, disease, and signaling pathways, and the transcriptional
      regulation of the C4ST-1 gene. Proper 4-sulfation of chondroitin by C4ST-1 plays
      a crucial role in the skeletal development and signaling events, and new evidence
      is suggestive of a potential role for C4ST-1 in human disease, including cancer.

PMID- 20807644
TI  - Roles of heparan sulfate in mammalian brain development current views based on
      the findings from Ext1 conditional knockout studies.
AB  - Development of the mammalian central nervous system proceeds roughly in four
      major steps, namely the patterning of the neural tube, generation of neurons from
      neural stem cells and their migration to genetically predetermined destinations,
      extension of axons and dendrites toward target neurons to form neural circuits,
      and formation of synaptic contacts. Earlier studies on spatiotemporal expression
      patterns and in vitro function of heparan sulfate (HS) suggested that HS is
      functionally involved in various aspects of neural development. Recent studies
      using knockout of genes involved in HS biosynthesis have provided more
      physiologically relevant information as to the role of HS in mammalian neural
      development. This chapter reviews the current understanding of the in vivo
      function of HS deduced from the phenotypes of conditional Ext1 knockout mice.

PMID- 20807645
TI  - Anticoagulant heparan sulfate to not clot--or not?
AB  - Vascular endothelial cells (ECs) produce anticoagulant heparan sulfate (HSAT+)-a
      small subpopulation of heparan sulfate (HS) containing a specific pentasaccharide
      motif with high affinity for plasma antithrombin (AT). This pentasaccharide is
      responsible for the anticoagulant action of therapeutic heparin, which
      dramatically catalyzes AT neutralization of coagulation proteases. Consequently,
      HSAT+ has been designated as "anticoagulant HS," and has long been thought to
      convey antithrombotic properties to the blood vessel wall. The Hs3st1 gene
      encodes HS 3-O-sulfotransferase-1, whose rate limiting action regulates EC
      production of HSAT+. To elucidate the biologic role of HSAT+, we generated Hs3st1
      /- knock-out mice that have undetectable EC HSAT+. Despite long held historic
      expectations, hemostasis was unaffected in Hs3st1-/- mice. In light of this
      surprising finding, herein we evaluate historic, biochemical, kinetic,
      physiologic, and molecular genetic studies of AT, heparin, and HSAT+. We find
      that a hemostatic role for HSAT+ cannot presently be excluded; however, HSAT+ may
      well not be essential for AT's anticoagulant function. Specifically, in the
      absence of glycosaminoglycans, physiologic levels of AT can neutralize
      coagulation proteases at a sufficiently high throughput to account for most of
      AT's anticoagulant function. Moreover, at the vessel wall surface,
      glycosaminoglycans distinct from HSAT+ may be the predominant catalysts of AT's
      anticoagulant activity. We then explore the possibility that HSAT+ regulates a
      less well known function of AT, anti-inflammatory activity. We find that Hs3st1-/
      mice exhibit a strong proinflammatory phenotype that is unresponsive to AT's
      anti-inflammatory activity. We conclude that the predominant function of HSAT+ is
      to mediate AT's anti-inflammatory activity.

PMID- 20807647
TI  - Hepatic heparan sulfate proteoglycans and endocytic clearance of triglyceride
      rich lipoproteins.
AB  - Hypertriglyceridemia, characterized by the accumulation of triglyceride-rich
      lipoproteins in the blood, affects 10-20% of the population in western countries
      and increases the risk of atherosclerosis, coronary artery disease, and
      pancreatitis. The etiology of hypertriglyceridemia is complex, and much interest
      exists in identifying and characterizing the biological and environmental factors
      that affect the synthesis and turnover of plasma triglycerides. Genetic studies
      in mice have recently identified that heparan sulfate proteoglycans are a class
      of receptors that mediate the clearance of triglyceride-rich lipoproteins in the
      liver. Heparan sulfate proteoglycans are expressed by endothelial cells that line
      the hepatic sinusoids and the underlying hepatocytes, and are present in the
      perisinusoidal space (space of Disse). This chapter discusses the dependence of
      lipoprotein binding on heparan sulfate structure and the identification of
      hepatocyte syndecan-1 as the primary proteoglycan that mediates triglyceride-rich
      lipoprotein clearance.

PMID- 20807648
TI  - Serglycin proteoglycan deletion in mouse platelets: physiological effects and
      their implications for platelet contributions to thrombosis, inflammation,
      atherosclerosis, and metastasis.
AB  - Serglycin is found in all nucleated hematopoietic cells and platelets, blood
      vessels, various reproductive and developmental tissues, and in chondrocytes. The
      serglycin knockout mouse has demonstrated that this proteoglycan is required for
      proper generation and function of secretory granules in several hematopoietic
      cells. The effects on platelets are profound, and include diminishing platelet
      aggregation responses and formation of platelet thrombi. This chapter will review
      cell-specific aspects of serglycin structure, its gene regulation, cell and
      tissue localization, and the effects of serglycin deletion on hematopoietic cell
      granule structure and function. The effects of serglycin knockout on platelets
      are described and discussed in detail. Rationales for further investigations into
      the contribution of serglycin to the known roles of platelets in thrombosis,
      inflammation, atherosclerosis, and tumor metastasis are presented.

PMID- 20807649
TI  - Congenital disorders of glycosylation with emphasis on loss of dermatan-4
      sulfotransferase.
AB  - The autosomal, recessively inherited, adducted thumb-clubfoot syndrome (ATCS)
      represents a generalized connective tissue disorder with congenital
      malformations, contractures of thumbs and feet, and a typical facial appearance.
      Cognitive development is normal in ATCS patients during childhood. ATCS is caused
      by homozygous nonsense and missense mutations in CHST14 which encodes an N
      acetylgalactosamine 4-O-sulfotransferase 1 (D4ST1) that catalyzes the 4-O
      sulfation of N-acetylgalactosamine in the repeating iduronic acid-alpha-1,3-N
      acetylgalactosamine disaccharide sequence to form dermatan sulfate (DS). ATCS
      mutations lead to either a decrease or a loss of D4ST1 activity, as revealed by
      absence of DS and an excess of chondroitin sulfate (CS) in patient's fibroblasts.
      Either of these effects or their combination might cause the observed clinical
      symptoms by altering the physiological pattern of dermatan and CS chains on their
      corresponding proteoglycans (PGs). ATCS is the only recognized disorder resulting
      from a defect that is specific to DS biosynthesis, and thus represents another
      class of the congenital glycosylation disorders. Congenital disorders of
      glycosylation (CDG) include all genetic diseases that result from defects in the
      synthesis of glycans. These disorders cause a wide range of human diseases, with
      examples emanating from all medical subspecialties. ATCS is the first human
      disorder that emphasizes a role for DS in human development and extracellular
      matrix maintenance.

PMID- 20807650
TI  - Heparan sulfate proteoglycans in amyloidosis.
AB  - Amyloidosis is a generic term for a group of diseases characterized by deposits
      in different organ systems of insoluble materials composed mainly of distinct
      fibrillar proteins named amyloid. Besides amyloid, heparan sulfate proteoglycan
      (HSPG), is commonly found in most amyloid deposits, suggesting that HS/HSPG may
      be functionally involved in the pathogenesis of amyloidosis. HS or HSPG is found
      to interact with a number of amyloid proteins, displaying a promoting effect on
      amyloid fibrilization in vitro. In addition, HS is reported to be involved in
      processing amyloid precursor proteins and mediate amyloid toxicity. Although
      little is known about the in vivo mechanisms regarding the codeposition of HS
      with amyloid proteins in different amyloid diseases, experiments carried out in
      animal models, especially in transgenic mouse model where HS molecular structure
      is modified, support an active role for HS in amyloidogenesis. Further
      experimental evidence is required to strengthen these in vivo findings at a
      molecular level. Animal models that express mutant forms of HS due to knockout of
      the enzymes involved in glycosaminoglycan (GAG) biosynthesis are expected to
      provide valuable tools for studying the implications of HS, as well as other
      GAGs, in amyloid disorders.

PMID- 20807646
TI  - Endothelial heparan sulfate in angiogenesis.
AB  - Heparan sulfate (HS) is a linear polysaccharide composed of 50-200 glucosamine
      and uronic acid (glucuronic acid or iduronic acid) disaccharide repeats with
      epimerization and various sulfation modifications. HS is covalently attached to
      core proteins to form HS-proteoglycans. Most of the functions of HS-proteoglycans
      are mediated by their HS moieties. The biosynthesis of HS is initiated by chain
      polymerization and is followed by stepwise modification reactions, including
      sulfation and epimerization. These modifications generate ligand-binding sites
      that modulate cell functions and activities of proteinases and/or proteinase
      inhibitors. HS is abundantly expressed in developing and mature vasculature, and
      understanding its roles in vascular biology and related human diseases is an area
      of intense investigation. In this chapter, we summarize the significant recent
      advances in our understanding of the roles of HS in developmental and
      pathological angiogenesis with a major focus on studies using transgenic as well
      as gene knockout/knockdown models in mice and zebrafish. These studies have
      revealed that HS critically regulates angiogenesis by playing a proangiogenic
      role, and this regulatory function critically depends on HS fine structure. The
      latter is responsible for facilitating cell-surface binding of various
      proangiogenic growth factors that in turn mediate endothelial growth signaling.
      In cancer, mouse studies have revealed important roles for endothelial cell
      surface HS as well as matrix-associated HS, wherein signaling by multiple growth
      factors as well as matrix storage of growth factors may be regulated by HS. We
      also discuss important mediators that may fine-tune such regulation, such as
      heparanase and sulfatases; and models wherein targeting HS (or core protein)
      biosynthesis may affect tumor growth and vascularization. Finally, the importance
      of targeting HS in other human diseases wherein angiogenesis may play
      pathophysiologic (or even therapeutic) roles is considered.

PMID- 20807651
TI  - Heparin as an inhibitor of cancer progression.
AB  - Heparin is frequently used in the treatment of cancer-associated thromboembolism.
      Accumulating clinical evidence indicates that cancer patients treated with
      unfractionated and low-molecular weight heparin (LMWH) survive longer than
      patients treated by other anticoagulants, especially patients in the early stage
      of the disease. Experimental analysis from a number of animal models constantly
      provides evidence for the ability of heparin to attenuate metastasis. The non
      anticoagulant activity of heparin on metastasis includes the ability to inhibit
      cell-cell-interaction through blocking of P- and L-selectin, to inhibit
      extracellular matrix protease heparanase, and to inhibit angiogenesis. This
      chapter summarizes current experimental evidence on the biology of heparin during
      cancer progression, with the focus on potential mechanism of heparin
      antimetastatic activity.

PMID- 20807652
TI  - Vascular dermatan sulfate and heparin cofactor II.
AB  - Heparin cofactor II (HCII) is a plasma protease inhibitor of the serpin family
      that inactivates thrombin by forming a covalent 1:1 complex. The rate of complex
      formation increases more than 1000-fold in the presence of dermatan sulfate (DS).
      Endothelial injury allows circulating HCII to enter the vessel wall, where it
      binds to DS and presumably becomes activated. Mice that lack HCII develop carotid
      artery thrombosis more rapidly than wild-type mice after oxidative damage to the
      endothelium. These mice also have increased arterial neointima formation
      following mechanical injury and develop more extensive atherosclerotic lesions
      when made hypercholesterolemic. Similarly, low plasma HCII levels appear to be a
      risk factor for atherosclerosis and in-stent restenosis in human subjects. These
      observations suggest that a major function of the HCII-DS system is to regulate
      the physiologic response to arterial injury.

PMID- 20807653
TI  - Diverse functions of glycosaminoglycans in infectious diseases.
AB  - Glycosaminoglycans (GAGs) are complex carbohydrates that are expressed
      ubiquitously and abundantly on the cell surface and in the extracellular matrix
      (ECM). The extraordinary structural diversity of GAGs enables them to interact
      with a wide variety of biological molecules. Through these interactions, GAGs
      modulate various biological processes, such as cell adhesion, proliferation and
      migration, ECM assembly, tissue repair, coagulation, and immune responses, among
      many others. Studies during the last several decades have indicated that GAGs
      also interact with microbial pathogens. GAG-pathogen interactions affect most, if
      not all, the key steps of microbial pathogenesis, including host cell attachment
      and invasion, cell-cell transmission, systemic dissemination and infection of
      secondary organs, and evasion of host defense mechanisms. These observations
      indicate that GAG-pathogen interactions serve diverse functions that affect the
      pathogenesis of infectious diseases.

PMID- 20807654
TI  - Molecular mechanism underlines heparin-induced thrombocytopenia and thrombosis.
AB  - Heparin-induced thrombocytopenia (HIT) with thrombosis is the most severe side
      effect of heparin administration. HIT patients may die or have permanent
      sequelae, such as a stroke or limb amputation. Contaminated heparin is associated
      with anaphylactic reactions and deaths by activating the contact system. It is
      also associated with high incidence of HIT via a yet unknown mechanism. This
      chapter shows that: (1) the contact system can be activated by a variety of
      unrelated molecules; (2) kallikrein directly cuts prothrombin to generate
      functional thrombin through contact system activation; and (3) while heparin
      contaminants, oversulfated heparin by-product (OS-HB), induce thrombin generation
      in both normal and HIT patient plasmas through contact system activation,
      authentic heparin induces thrombin activities only in HIT patient plasmas
      containing autoantibodies against protein/heparin complex. These data suggest
      that the negatively charged IgG/protein/heparin or OS-HB complex activate the
      contact system and produce thrombin in human plasma and thrombin partially
      activates the platelets allowing subsequent platelet activation through IgG/Fc
      receptor II signaling. The newly discovered mechanism of heparin-induced thrombin
      activity could explain the increased incidence of HIT in patients exposed to
      contaminated heparin. Furthermore, the assays used in these studies would be
      valuable for HIT diagnosis, prevention, and treatment.

PMID- 20807655
TI  - Chondroitin sulfate and abnormal contact system in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a heterogeneous autoimmune disease that affects 1%
      of the population worldwide. In the K/BxN mouse model of RA, autoantibodies
      specific for glucose-6-phosphate isomerase (GPI) from these mice can transfer
      joint-specific inflammation to normal mice. The binding of GPI/autoantibody to
      the cartilage surface is a prerequisite for autoantibody-induced joint-specific
      inflammation in the mouse model. Chondroitin sulfate (CS) on cartilage surface is
      the long sought high-affinity receptor for GPI. The binding affinity and
      structural differences between mouse paw/ankle CS and knee/elbow CS correlate
      with the distal to proximal disease severity in these joints. The data presented
      in this chapter indicate that autoantigen/autoantibodies in blood circulation
      activate contact system to produce vasodilators to allow immune complex, protein
      aggregates, and other plasma proteins to get into the joints. Cartilage surface
      CS binds and retains autoantigen/autoantibodies. The CS/autoantigen/autoantibody
      complexes could induce C3a and C5a production through contact system activation.
      C3a and C5a trigger degranulation of mast cells, which further recruit plasma
      contact system and complement proteins, immune cells, and immune activation
      factors to facilitate joint-specific tissue destruction. Therefore, either
      reducing autoantibody production or inhibiting autoantibody-induced contact
      system activation might be effective in RA prevention.

PMID- 20807656
TI  - Activated contact system and abnormal glycosaminoglycans in lupus and other auto-
      and non-autoimmune diseases.
AB  - Systemic lupus erythematosus (SLE), heparin-induced thrombocytopenia (HIT),
      rheumatoid arthritis (RA) are marked by the presence of autoantibodies against
      negatively changed DNA, phospholipids, heparin, and chondroitin sulfate,
      respectively. Heparin/protein complexes induce contact system activation in HIT
      patient plasmas. The activated contact system generates thrombin. Thrombin is
      responsible for thrombosis, a common cause of death and disabilities for both HIT
      and SLE. In this chapter, we analyze plasma contact system proteins, thrombin-
      and kallikrein-like activities, glucosamine and galactosamine content from SLE-,
      RA-, osteoarthritis (OA)-, and psoriasis (Ps)-patient plasmas in addition to
      pooled 30+ healthy patient plasmas. We found that all SLE patient plasmas
      exhibited abnormal contact systems marked by the absence of high molecular weight
      kininogen, the presence of processed C1 inhibitor (C1inh), the display of
      abnormal thrombin- and kallikrein-like activities, and increased levels of plasma
      glucosamine and galactosamine. Different patterns of contact system activation
      distinguish SLE, RA, and Ps whereas no contact system activation is observed in
      normal and OA patient plasmas. The presence of paradoxical "lupus anticoagulants"
      in certain thrombosis-prone SLE patient plasmas, marked by delayed clotting in
      clinical plasma test, was explained by the consumption of contact system
      proteins, especially high molecular weight kininogen. Finally, we discovered that
      mouse and human SLE autoantibodies bind to cell surface GAGs with structural
      selectivity. In conclusion, markers of abnormal contact system activation
      represent potential new targets for autoimmune disease diagnosis, prevention, and
      treatment. These markers might also be useful in monitoring SLE activity/severity
      and in pinpointing patients with SLE-associated arthritis and psoriasis.

PMID- 20807657
TI  - Glycosaminoglycans and activated contact system in cancer patient plasmas.
AB  - Oncogenic mutations create cancer cells. Cancer cells require thrombin for
      growth, angiogenesis, and metastasis. All cancer patients display a
      hypercoagulable state, which includes platelet activation, blood coagulation,
      complement activation, vasodilatation, and inflammation. This often results in
      thrombosis, the second leading cause of death in cancer patients. It is
      established that chemically oversulfated glycosaminoglycans (GAGs) induce
      thrombin generation through contact system activation in human plasma. Thrombin
      is responsible for thrombosis. In this chapter, we show that plasmas from lung
      cancer patients contain activated contact systems apparent by the absence of high
      molecular weight kininogen and processed C1inh, by abnormal kallikrein and
      thrombin activities, and by increased glucosamine, galactosamine, and GAG levels.
      Activated contact systems were also evident in plasmas from breast, colon, and
      pancreatic cancer patients. These data suggest that GAGs or other molecules
      produced by tumors induce abnormal thrombin generation through contact system
      activation. Therefore, the contact system and glycans represent new targets for
      cancer diagnosis, prevention, and treatment.

PMID- 20807658
TI  - Levels of salivary stress markers in patients with anxiety about halitosis.
AB  - OBJECTIVE: To investigate the relationship between salivary stress markers and
      mental stress states in patients complaining of oral malodour. The utility of the
      salivary stress markers in assessment of mental conditions of those patients was
      also investigated. DESIGN: The study population included 74 patients, aged 20-59
      years, who complained of oral malodour and were referred to the Breath Odor
      Clinic at Tokushima University Hospital. Patients were classified into two
      groups, genuine halitosis (GH) and psychosomatic halitosis (PH), according to the
      results of organoleptic rating measurement. All patients were subjected to
      examination by the Cornell Medical Index (CMI) Health Questionnaire. Resting
      saliva was collected and levels of salivary IgA, cortisol and chromogranin A were
      determined by ELISA. Twenty-three volunteers not complaining of halitosis were
      included as the control group. Kruskal-Wallis test and Mann-Whitney's U-test were
      used for statistical analysis. RESULTS: A significant increase was observed in
      the concentrations of salivary cortisol in the PH group as compared with GH and
      control groups (p<0.05). Concentrations of IgA and chromogranin A in saliva were
      not significantly different among the three groups. In addition, higher salivary
      cortisol concentrations were found in CMI scale III and IV (tendency towards
      neurosis) than in scale I and II (normal) (p<0.05). Since salivary cortisol
      reflects a status of chronic stress condition, psychosomatic halitosis might be
      closely related to this state of chronic stress. CONCLUSIONS: Determination of
      cortisol levels in saliva may provide useful information for evaluating the
      mental status of patients complaining of halitosis.

PMID- 20807659
TI  - Age at onset of multiple sclerosis is correlated to use of combined oral
      contraceptives and childbirth before diagnosis.
AB  - The aim of this study was to evaluate whether age of onset of multiple sclerosis
      is related to use of combined oral contraceptives and/or timing of childbirth.
      The results showed that use of combined oral contraceptives and childbirth before
      the first multiple sclerosis symptom was correlated to a higher mean age at the
      onset of the disease.

PMID- 20807660
TI  - Comparison of hypercrosslinked polystyrene columns for the separation of nitrogen
      group-types in petroleum using High Performance Liquid Chromatography.
AB  - High performance liquid chromatography in a quasi-normal phase mode (QNP) is used
      to separate the nitrogen group-types (pyrrole and pyridine) that are found in
      petroleum. A new type of stationary phase, hypercrosslinked polystyrene, is used
      to achieve this separation. Three different hypercrosslinked polystyrene
      stationary phases are compared under quasi-normal phase mode; a commercial 5-HGN
      packing, and two hypercrosslinked phases on silica particles. The utility of the
      columns for petroleum-based separations was explored with the use of 21
      analytical standards. Partial elucidation of adsorption retention mechanisms for
      the columns are shown, as well as a comparison of retention characteristics for
      the three columns. The silica particle column derived with toluene (HC-Tol) was
      found to have the best selectivity for nitrogen group-types and polycyclic
      aromatic hydrocarbons (PAHs), attaining a separation under gradient conditions in
      less than 30 min.

PMID- 20807661
TI  - Thermodynamic and kinetic characterization of a bridged-ethylene hybrid C18
      stationary phase.
AB  - In this study, a series of polycyclic aromatic hydrocarbons (PAHs) and nitrogen
      containing polycyclic aromatic hydrocarbons (NPAHs) is separated on a hybrid
      stationary phase using methanol and acetonitrile mobile phases. Temperature is
      varied from 283 to 313 K in order to determine thermodynamic and kinetic
      parameters of the separation. Thermodynamic behavior is characterized by the
      retention factor and associated changes in molar enthalpy, whereas kinetic
      behavior is characterized by the rate constants and associated activation
      energies. In this study, the retention factors for the NPAHs are smaller than
      those for the parent PAHs in methanol, while they are more similar to the parent
      PAHs in acetonitrile. The changes in molar enthalpy are very similar for all
      solutes, yet are more negative in acetonitrile than in methanol. The rate
      constants for the NPAHs are smaller than those for their parent PAHs in both
      mobile phases. Moreover, the rate constants in acetonitrile are one to four
      orders of magnitude smaller than those in methanol. Based on these thermodynamic
      and kinetic results, the hybrid stationary phase is compared to traditional
      silica stationary phases. In addition, the relative contributions from the
      partition and adsorption mechanisms are discussed.

PMID- 20807663
TI  - Increased level of serum interleukin-1 receptor antagonist subsequent to
      resolution of clinical symptoms in patients with West syndrome.
AB  - The aim of this study was to evaluate whether proconvulsive interleukin-1beta (IL
      1beta) and anticonvulsive IL-1 receptor antagonist (IL-1Ra) are markers of the
      effectiveness of treatment in patients with West syndrome (WS). We analyzed serum
      and cerebrospinal fluid (CSF) levels of IL-1beta and IL-1Ra in 13 patients with
      WS. The serum IL-1Ra levels postimprovement (average, 384.6 pg/ml) in clinical
      and electroencephalographic (EEG) findings were significantly higher than the
      preimprovement values (average, 240.6 pg/ml). No significant difference in the
      preimprovement serum IL-1Ra levels was noted between the anticonvulsant (AED)
      response and adrenocorticotropic hormone (ACTH)-response groups (260.0 pg/ml, n=7
      vs. 218.0 pg/m, n=6) and the cryptogenic and symptomatic groups (290.1 pg/ml, n=4
      vs. 218.3 pg/m, n=9), respectively; as for the preimprovement CSF levels, the AED
      response group (114.5 pg/m; n=3) and ACTH-response groups (138.0 pg/m; n=6) and
      the cryptogenic (59.3 pg/m; n=3) and symptomatic groups (165.6 pg/m; n=6),
      respectively. Serum and CSF IL-1beta levels were detected only in 3 patients
      preimprovement. Serum IL-1Ra levels were elevated subsequent to resolution of
      clinical and EEG findings in WS patients. A larger study should be conducted to
      clarify whether an immunological processes are concerned with the pathophysiology
      of WS.

PMID- 20807664
TI  - Comparison of a direct Factor Xa inhibitor, edoxaban, with dalteparin and
      ximelagatran: a randomised controlled trial in healthy elderly adults.
AB  - INTRODUCTION: Edoxaban (the free base of DU-176b) is a new, oral direct Factor Xa
      inhibitor. This is the first study to compare the hemostatic response to
      edoxaban, ximelagatran, and dalteparin in healthy, elderly adults. MATERIALS AND
      METHODS: In this open-label, active-controlled clinical trial, 40 adults (65-75
      years), were randomised to: oral edoxaban (60 mg, twice-daily, 7 doses),
      subcutaneous dalteparin (5000 IU, once-daily, 4 doses), oral ximelagatran (24 mg,
      twice-daily, 7 doses) or no drug. Blood samples were taken before, and 1.5, 4,
      12, 24, 72, 84, 96, 108, 120, and 144 hours after, the first dose. The primary
      outcomes were changes in thrombin-antithrombin complex, prothrombin fragment 1+2
      and D-dimer, and adverse events. Additional biomarkers of coagulation, and
      endothelial cell and platelet activation were compared (ANOVA). RESULTS: All
      subjects completed the study. Inhibition of thrombin generation lag time, peak,
      and constant velocity index were significantly greater, and extended for a longer
      period of time, following edoxaban administration, compared with dalteparin. We
      found that the traditional assay for anti-FXa activity was not appropriate for
      the new anticoagulants. Biomarker changes following edoxaban administration
      (including prolongation of prothrombin time) reflected inhibition of Factor Xa;
      there was no effect on platelet, tissue factor or endothelial activation. There
      were no clinically significant changes in primary outcomes. No serious adverse
      events were reported. CONCLUSION: Oral administration of edoxaban resulted in
      effective Factor Xa and TG inhibition, and was well-tolerated. Studies are needed
      to confirm edoxaban (60 mg daily) use in clinical practice. SPONSORSHIP: Daiichi
      Sankyo Pharma Development.

PMID- 20807665
TI  - Actin as a potential target for decavanadate.
AB  - ATP prevents G-actin cysteine oxidation and vanadyl formation specifically
      induced by decavanadate, suggesting that the oxometalate-protein interaction is
      affected by the nucleotide. The ATP exchange rate is increased by 2-fold due to
      the presence of decavanadate when compared with control actin (3.1*10(-3) s(-1)),
      and an apparent dissociation constant (k(dapp)) of 227.4+/-25.7 MUM and 112.3+/
      8.7 MUM was obtained in absence or presence of 20 MUM V(10), respectively.
      Moreover, concentrations as low as 50 MUM of decameric vanadate species (V(10))
      increases the relative G-actin intrinsic fluorescence intensity by approximately
      80% whereas for a 10-fold concentration of monomeric vanadate (V(1)) no effects
      were observed. Upon decavanadate titration, it was observed a linear increase in
      G-actin hydrophobic surface (2.6-fold), while no changes were detected for V(1)
      (0-200 MUM). Taken together, three major ideas arise: i) ATP prevents
      decavanadate-induced G-actin cysteine oxidation and vanadate reduction; ii)
      decavanadate promotes actin conformational changes resulting on its inactivation,
      iii) decavanadate has an effect on actin ATP binding site. Once it is
      demonstrated that actin is a new potential target for decavanadate, being the ATP
      binding site a suitable site for decavanadate binding, it is proposed that some
      of the biological effects of vanadate can be, at least in part, explained by
      decavanadate interactions with actin.

PMID- 20807666
TI  - A prospective study of lipids and serotonin as risk markers of violence and self
      harm in acute psychiatric patients.
AB  - Cross-sectional studies have reported an association between lipids and serotonin
      levels and aggression, but a literature search revealed a paucity of prospective
      studies. Subjects of the present naturalistic study were 254 of all (489)
      involuntary and voluntary acutely admitted patients to a psychiatric hospital
      during 1year. Serum lipids and platelet serotonin at admission were prospectively
      compared with recorded intra-institutional and 1-year post-discharge violence and
      self-harm. Total cholesterol had a significant negative relationship to inpatient
      suicidal behaviour and inpatient violent behaviour and to 3-month post-discharge
      violent behaviour. Triglycerides were a significant marker of inpatient self
      mutilation and of self-mutilation in combination with suicidal behaviour at 3 and
      12 months of follow-up. High-density lipoprotein (HDL) had a significant negative
      relationship to violence at 12-months, and to repeated violence in seven patients
      with two or more admissions. The post-discharge relationships between total
      cholesterol and violence and between triglycerides and self-harm remained
      significant even when controlling for other possible explanatory variables in a
      multivariate model. Results did not change after controlling for current
      medication at admission. There was no association between platelet serotonin and
      violence or self-harm. Future research may examine if lipid measurements add
      incremental validity to established clinical risk assessment procedures of
      violent and self-harm behaviour.

PMID- 20807667
TI  - Nonsuicidal self-injury in adolescence: prospective rates and risk factors in a
      21/2 year longitudinal study.
AB  - Little is known about which risk factors longitudinally predict non-suicidal self
      injury (NSSI) during adolescence, a period when these self-injurious behaviors
      become alarmingly prevalent. We prospectively studied the rates, course, and
      longitudinal prediction of NSSI from early through middle adolescence with a
      community sample of 103 youth (ages 11-14) who were assessed for NSSI at baseline
      and 2 1/2 years later (94% retention; final N=97). Multiple risk factors
      (temperament, cognitive and interpersonal vulnerabilities, stressors; youths' and
      mothers' depression) were examined as prospective predictors of NSSI over the
      21/2 year follow-up. Analyses showed that 18% of youth engaged in NSSI over the
      21/2-year follow-up; 14% for the first time. Distal risks (assessed at baseline)
      that differentiated youth who engaged in NSSI from those who did not included
      negative cognitive style and mothers' prior depression. Proximal factors
      (assessed 2 years after baseline) that differentiated NSSI from non-NSSI youth
      included stressors, depressive symptoms, poor relationship quality, excessive
      reassurance seeking, and mothers' onset of depression. Several of these factors
      predicted new engagement of NSSI over 21/2 years.

PMID- 20807668
TI  - The effect of dexamethasone on clock gene mRNA levels in bovine neutrophils and
      lymphocytes.
AB  - Circadian rhythms are driven by oscillating expression of a family of
      transcription factors called clock genes. In rodents, clock genes drive circadian
      rhythms in white blood cell function, and glucocorticoids are believed to
      regulate these rhythms. Little is known about circadian rhythms of cattle white
      blood cells. The objectives of this study were: (1) to quantify mRNA levels of
      clock genes in neutrophils and lymphocytes over 24h in healthy steers; and (2) to
      quantify effects of dexamethasone on clock gene mRNA levels in bovine neutrophils
      and lymphocytes. We hypothesized that bovine neutrophils and lymphocytes would
      display 24h variations in clock gene mRNA levels and that those patterns would be
      disrupted by glucocorticoid treatment. Six Holstein steers were injected with 0
      or 0.10mg/kg body weight dexamethasone according to a crossover design.
      Neutrophils and lymphocytes were collected from jugular blood at 0, 4, 8, 12, 16,
      20, and 24h relative to treatment administration. Neutrophil and lymphocyte mRNA
      levels of the clock genes Clock, Bmal1, Per1, Per2, Cry1, Cry2, Rev-erbalpha, and
      CK1E were quantified. For neutrophils, an interaction between treatment and time
      was found for Clock, Cry1, and CK1E. Time affected Clock, Per1, Cry1, Rev
      erbalpha, and CK1E. For all of those genes except Per1, neutrophils from control
      steers displayed 24h changes of mRNA levels characteristic of circadian regulated
      cells. The dexamethasone treatment increased neutrophil mRNA levels of Per1,
      decreased Clock, Cry1, Cry2, and Rev-erbalpha, and tended to decrease Bmal1.
      These results suggest that circadian rhythms have the potential to impact bovine
      neutrophil function, and that glucocorticoid-induced disruption of neutrophil
      circadian rhythms may contribute to periparturient immunosuppression. For
      lymphocytes, an interaction between treatment and time was observed for Per1 and
      tended to occur for Per2 and Cry2. Although time affected Per1 and Rev-erbalpha,
      distinct 24h patterns of lymphocyte clock gene mRNA levels were not evident as
      they were in neutrophils. Treatment increased Per1 and decreased Cry2, but the
      magnitude of the treatment effect was small. In summary, 24h patterns in clock
      gene mRNA levels were observed in bovine neutrophils and to some degree in
      lymphocytes, and these patterns were disrupted by dexamethasone administration.
      Although further research is needed, individual variation in white blood cell
      circadian rhythms and glucocorticoid responsiveness may help to explain
      individual differences in periparturient disease susceptibility.

PMID- 20807669
TI  - Psychological well-being of Thai nursing students.
AB  - BACKGROUND: The psychological well-being of nursing students is a very important
      component in the training and development of future nurses. While previous
      studies have explored different aspects of nursing students' mental and
      psychological health in various countries, they have given little attention to
      comparing nursing students with their non-nursing student peers. The present
      study investigated the differences between nursing students and non-nursing
      students in Thailand with regard to their psychological well-being. The gender
      effect was also examined. METHOD: Four hundred students were included in this
      study (200 nursing students and 200 non-nursing students). Participants completed
      a demographic questionnaire and four psychological instruments that examined
      their self-esteem, life satisfaction, depression, and social difficulties.
      RESULTS: Overall, compared to their non-nursing counterparts, nursing students
      were found to score significantly higher on self-esteem and life satisfaction and
      reported lower levels of depression and social difficulties. Gender was also
      found to have a significant main effect on participants' social difficulties.
      Several recommendations for improving the mental health and psychological well
      being of nursing students are discussed.

PMID- 20807670
TI  - An evaluation of a European teacher exchange programme.
AB  - This longitudinal study evaluated a European teacher exchange programme within a
      UK School of Nursing and Midwifery. A cross case study design was employed over a
      three year period. A range of data methods were used which gave a clear, detailed
      and rich picture of the exchange experience. Overall analysis of the data
      generated two key themes, namely that of value and role identity. The study
      highlighted factors which were deemed to have positive and negative influences on
      the teacher exchange experience. It is concluded that a teacher exchange
      programme is of value to the School, by aiding personal and professional
      development and internationalisation. Recommendations from the study are included
      in the paper.

PMID- 20807671
TI  - Exploring nursing students' decision-making skills whilst in a Second Life
      clinical simulation laboratory.
AB  - AIM: To explore nursing students' decision-making skills through the use of a 3D
      virtual environment such as Second Life. METHOD: An exploratory qualitative
      evaluation of the students' experience of learning decision-making skills whilst
      in a Second Life clinical simulation laboratory. A convenience sample of five
      third year student nurses entered a simulated world environment where they cared
      for six patients over 1h. The written communication text from the Second Life
      scenario was saved into a Microsoft Word document. Additionally a semi-structured
      tape-recorded one to one interview was conducted immediately after the Second
      Life simulation in order to explore the students' decision-making skills.
      RESULTS: The communication text illustrated that the majority of decisions (n=21)
      were made in response to a situation or a patient request, therefore 'reactive'
      rather than proactive (n=9). Only one student carried out a vital signs
      assessment on a newly admitted patient (Willie). The interviews produced two
      themes, performing decision-making and improving learning. The absence of 'visual
      cues' such as pre-operative checklists, vital sign observation charts and 'Nil by
      Mouth' signs may offer a rationale for why students were more reactive.
      CONCLUSION: Further work is required for students to practice decision-making
      skills. With further development the innovative 3D virtual worlds such as Second
      Life could provide this experience.

PMID- 20807672
TI  - Safety and efficacy of defibrillator charging during ongoing chest compressions:
      a multi-center study.
AB  - BACKGROUND: Pauses in chest compressions during cardiopulmonary resuscitation
      have been shown to correlate with poor outcomes. In an attempt to minimize these
      pauses, the American Heart Association recommends charging the defibrillator
      during chest compressions. While simulation work suggests decreased pause times
      using this technique, little is known about its use in clinical practice.
      METHODS: We conducted a multi-center, retrospective study of defibrillator
      charging at three US academic teaching hospitals between April 2006 and April
      2009. Data were abstracted from CPR-sensing defibrillator transcripts. Pre-shock
      pauses and total hands-off time preceding the defibrillation attempts were
      compared among techniques. RESULTS: A total of 680 charge-cycles from 244 cardiac
      arrests were analyzed. The defibrillator was charged during ongoing chest
      compressions in 448 (65.9%) instances with wide variability across the three
      sites. Charging during compressions correlated with a decrease in median pre
      shock pause [2.6s (IQR 1.9-3.8) vs 13.3s (IQR 8.6-19.5); p < 0.001] and total
      hands-off time in the 30s preceding defibrillation [10.3s (IQR 6.4-13.8) vs 14.8s
      (IQR 11.0-19.6); p < 0.001]. The improvement in hands-off time was most
      pronounced when rescuers charged the defibrillator in anticipation of the pause,
      prior to any rhythm analysis. There was no difference in inappropriate shocks
      when charging during chest compressions (20.0% vs 20.1%; p = 0.97) and there was
      only one instance noted of inadvertent shock administration during compressions,
      which went unnoticed by the compressor. CONCLUSIONS: Charging during compressions
      is underutilized in clinical practice. The technique is associated with decreased
      hands-off time preceding defibrillation, with minimal risk to patients or
      rescuers.

PMID- 20807673
TI  - A quantitative analysis of subjective, cognitive, and physiological
      manifestations of the acute tobacco abstinence syndrome.
AB  - RATIONALE: Previous studies have documented the existence of signs and symptoms
      of the acute tobacco abstinence syndrome; however, less attention has been paid
      to quantifying the magnitude of these effects. OBJECTIVE: The present study
      quantified the relative magnitude of subjective, cognitive, and physiological
      manifestations of acute tobacco abstinence. METHOD: Smokers (N=203, >= 15
      cig/day) attended two counterbalanced laboratory sessions, one following 12-h of
      abstinence and the other following ad-lib smoking. At both sessions, they
      completed an extensive battery of self-report measures (withdrawal, affect,
      hunger, craving, subjective attentional bias towards smoking cues), physiological
      assessments (heart rate, blood pressure, brain EEG), and cognitive performance
      tasks (psychomotor processing, sustained attention, objective attentional bias).
      RESULTS: Abstinence effects were largest for craving, subjective attentional
      bias, negative affect, overall withdrawal severity, concentration difficulty,
      hunger, and heart rate. Effects were moderate for positive affect and EEG power.
      Effects were small, but reliable, for psychomotor speed, sustained attention, and
      somatic symptoms. Effects on performance-based indices of attentional bias
      towards smoking-related cues were small and reliable for some indices but not
      others. Effects were small and inconsistent for blood pressure and EEG frequency.
      Variation in internal consistency accounted for 33% of the variation in
      abstinence effect sizes across measures. CONCLUSIONS: There was a wide range of
      effect sizes both across and within domains, indicating that the acute tobacco
      abstinence syndrome is not a monotonic phenomenon. These findings may be
      indicative of the relative magnitudes of signs and symptoms that the average
      smoker may exhibit during acute abstinence.

PMID- 20807674
TI  - Defining and understanding success at smoking reduction: a mixed-methods study.
AB  - Much is known about the outcomes of different smoking reduction and cessation
      programs. However there is a lack of information about the degree to which such
      programs can achieve successes after initial failures. This study evaluated the
      patterns of success and failure during a smoking reduction intervention with a
      sample of 164 adult smokers (mean age 62; mean baseline smoking rate 21.2
      cigarettes per day) who wanted to reduce their smoking but were not ready to
      attempt cessation. Success was defined by both self-reported number of cigarettes
      smoked assessed during counseling calls and carbon monoxide levels at 3 and 12
      month follow-ups. There was a strong relationship between initial success/failure
      and eventual outcome using both assessment methods, and a moderate relationship
      between success categorization using the different methods (r=.43). Qualitative
      contextual data identified that types of travel, work and family environmental
      barriers experienced differed across success categories. This research confirms
      the importance of initial success in changing addictive behaviors and suggests
      directions for future research; including ways to enhance initial success, and
      the suggestion that more study is needed regarding the generalizability of these
      findings across settings and behaviors.

PMID- 20807675
TI  - Pneumatosis intestinalis after liver transplantation.
AB  - PURPOSE: To evaluate clinical features and CT findings of pneumatois intestinalis
      in recipients following liver transplantation and to determine whether certain
      clinical and CT findings enable differentiation of indolent pneumatois
      intestinalis from fulminant cases. MATERIALS AND METHODS: This retrospective
      study was approved by our institutional review board, with informed consent
      waived. Among 2080 liver transplantation recipients at our institution between
      January 1998 and April 2008, 22 (1%) presented with pneumatois intestinalis on
      postoperative follow-up. Patients were divided into recovery and mortality
      groups, and then clinical features and CT findings were compared between two
      groups. RESULTS: Although indolent pneumatois intestinalis more frequently
      presented incidentally (61%) after 2 weeks of surgery (89%) than fulminant
      pneumatois intestinalis (0, 50%), there were no statistically significant
      differences (P=.14, .09). Right colon was affected in the recovery group without
      exception (n=18,100%), and all four patients (100%) in mortality group showed
      small bowel involvement (P<.05). Caliber changes of superior mesenteric artery
      and vein in mortality group were significantly greater (49.6%, 67.0%) than those
      in recovery group (101.7%, 99.0%) (P<.05, respectively). Pneumatois intestinalis
      in mortality group more commonly accompanied portomesenteric air-embolism,
      visceral infarction, hemorrhagic ascites, and small bowel ileus than indolent
      counterpart (P<.05, respectively). CONCLUSION: Typical indolent pneumatois
      intestinalis is found incidentally later than 2 weeks of liver transplantation
      surgery, but there is some overlap between indolent and fulminant pneumatois
      intestinalis in terms of onset and mode of presentation. Among CT findings, grave
      signs are small bowel involvement, caliber changes in mesenteric vessels,
      portomesenteric air-embolism, visceral infarction, hemorrhagic ascites, and small
      bowel ileus.

PMID- 20807676
TI  - Systematic review of the effect of dental staff behaviour on child dental patient
      anxiety and behaviour.
AB  - OBJECTIVES: To review the literature, of the past 30 years, on the effects of
      dental staff behaviour on the anxiety and behaviour of child dental patients;
      especially to determine staff behaviours that reduce anxiety and encourage
      cooperation of children. METHODS: A systematic literature review was conducted
      using PubMed, Web of Science, The Cochrane Library, PsycINFO, Embase and CINAHL.
      RESULTS: Initial search returned 31 publications of which 11 fulfilled the
      criteria for review. Among seven studies that measured anxiety, four used
      validated measures. Five observational studies coded behaviour using Weinstein et
      al.'s (1982) coding scheme [1]. An empathic working style and appropriate level
      of physical contact accompanied by verbal reassurance was found to reduce fear
      related behaviours in children. Findings regarding positive reinforcement and
      dentists' experience increasing cooperative behaviour were inconsistent.
      CONCLUSIONS: Measures for anxiety and behaviour varied across studies.
      Relationships between certain dental staff behaviours and child anxiety/behaviour
      were reported. However, limited work was identified and research using improved
      sampling, measurement and statistical approach is required. PRACTICE
      IMPLICATIONS: Understanding what routine clinical behaviour of dental staff
      affects children's dental anxiety/behaviour will inform investigators of how
      children comply and help staff be aware the significance of their daily behaviour
      on treatment success.

PMID- 20807677
TI  - Anatomical and immunohistochemical considerations on the microinnervation of
      trachea in humans.
AB  - The anatomy of the tracheal microinnervation is understudied in humans; the
      purpose of our study was to fill this gap by working on human adult tracheas, to
      compare the results with those obtained from animal studies, and to checking
      whether or not these studies are suitable to be translated from comparative to
      the human anatomy. The study was designed as a qualitative one. The present work
      was performed on human adult tracheas dissected out in 15 human adult cadavers.
      Microdissections were performed in eight tracheas and revealed the outer
      peritracheal plexus, segmentally supplied and distributed to trachea and
      esophagus, with longitudinal intersegmentary anastomoses but also with bilateral
      interrecurrential anastomoses previously undescribed in anatomy. Seven different
      tracheas were transversally cut and paraffin embedded. Histological stains (HE,
      toluidine blue, luxol fast blue, Giemsa on tissues and trichrome Gieson) and
      immunohistochemistry using primary antibodies for nNOS, neurofilament, SMA and
      the cocktail of citokeratines CK AE1-AE3+8/18 were done. According to the
      histological individual variation, the neural layers of the posterior wall of the
      human trachea could be considered as it follows: (a) an outer neural layer,
      ganglionated, associated with the connective covering layers, adventitia and the
      posterior fibroelastic membrane (external elastic lamina); (b) a submucosal
      ganglionated neural layer, mainly with juxtaglandular microganglia that may
      expand, as glands do, through the outer covering layers; (c) intrinsic nerves of
      the transverse trachealis muscle; (d) the neural layer intrinsic to the
      longitudinal elastic band (internal elastic lamina) and supplied from the inner
      submucosa; (e) the neural plexus of the lamina propria, with scarcely distributed
      neurons. We also bring here the first evidences for the in vivo nNOS phenotype of
      mast cells that were identified, but not exclusively, within the trachealis
      muscle.

PMID- 20807678
TI  - Oncogene-induced senescence: the bright and dark side of the response.
AB  - In late 1990s, it was shown that activated oncogenes are able to induce
      senescence. Since then large leaps in understanding this phenomenon have been
      achieved. There is substantial evidence supporting oncogene-induced senescence
      (OIS) as a potent antitumor barrier in vivo. Multiple pathways participating in
      cell cycle regulation, DNA damage signaling, immune response, and bioenergetics
      regulate the process. Despite its beneficial effects the senescent cell is
      thought to promote carcinogenesis and age-related disease in a nonautonomous
      manner. Here, we highlight the works dealing with all these aspects and discuss
      the studies proposing therapeutic exploitation of OIS.

PMID- 20807680
TI  - Monitoring differences in gene expression levels and polyhydroxyalkanoate (PHA)
      production in Pseudomonas putida KT2440 grown on different carbon sources.
AB  - Pseudomonas putida has a variety of potential uses in bioremediation and
      biosynthesis of biodegradable plastics. P. putida is able to utilize a wide range
      of carbon sources. In this study, P. putida KT2440 was grown on glucose,
      glycerol, citrate, or fatty acid (lauric acid) as the sole carbon source.
      Differences in expression levels of genes involved in the Entner-Doudoroff
      pathway, glycerol metabolism, TCA cycle and beta-oxidation were detected using
      quantitative real-time PCR. When glycerol was the sole carbon source, expression
      of genes related to glycerol metabolism was enhanced with the exception of the
      negative regulon gene glpR. There were no significant differences in expression
      levels of genes that putatively encode enzymes involved in the Entner-Doudoroff
      pathway for cells grown on glucose as compared to cells grown on other carbon
      sources. Exceptions to this trend were the ABC transporter genes. Genes encoding
      enzymes selected from the TCA cycle all showed higher expression levels in cells
      grown on citrate. Two genes for beta-oxidation enzymes, fadB and the long-chain
      fatty acid transporter gene, showed higher expression level when cells were grown
      on lauric acid. Genes encoding enzymes involved in PHA synthesis, phaC1, phaC2,
      phaZ, and phaJ4, all showed higher expression levels when cells were grown on
      lauric acid. This study has identified genes involved in the metabolism of
      different carbon sources and PHA synthesis. This information will be invaluable
      to understand how genes are regulated and construct transgenic strains to utilize
      carbon sources more efficiently and better produce PHAs.

PMID- 20807679
TI  - A spectroscopic comparison of selected Chinese kaolinite, coal bearing kaolinite
      and halloysite--a mid-infrared and near-infrared study.
AB  - Mid-infrared (MIR) and near-infrared (NIR) spectroscopy have been compared and
      evaluated for differentiating kaolinite, coal bearing kaolinite and halloysite.
      Kaolinite, coal bearing kaolinite and halloysite are the three relative abundant
      minerals of the kaolin group, especially in China. In the MIR spectra, the
      differences are shown in the 3000-3600 cm-1 between kaolinite and halloysite. It
      cannot obviously differentiate the kaolinite and halloysite, leaving alone
      kaolinite and coal bearing kaolinite. However, NIR, together with MIR, gives us
      the sufficient evidence to differentiate the kaolinite and halloysite, especially
      kaolinite and coal bearing kaolinite. There are obvious differences between
      kaolinite and halloysite in all range of their spectra, and they also show some
      difference between kaolinite and coal bearing kaolinite. Therefore, the
      reproducibility of measurement, signal to noise ratio and richness of qualitative
      information should be simultaneously considered for proper selection of a
      spectroscopic method for mineral analysis.

PMID- 20807681
TI  - Intensive glucose control and cardiovascular outcomes in type 2 diabetes.
AB  - Numerous observational studies have clearly shown a relationship between
      hyperglycaemia and cardiovascular (CV) disease. However, the United Kingdom
      Prospective Diabetes Study (UKPDS), which involved subjects with newly diagnosed
      type 2 diabetes, just failed to show that intensive glucose control significantly
      reduces CV events. The results of three subsequent large randomised controlled
      trials, the Action to Control Cardiovascular Risk in Diabetes (ACCORD), Action in
      Diabetes and Vascular Disease Preterax and Diamicron Modified Release Controlled
      Evaluation (ADVANCE) and the Veterans Administration Diabetes Trial (VADT), that
      involved approximately 25,000 subjects with established type 2 diabetes also
      failed to show that intensive glucose control, aiming for a glycated haemoglobin
      (HbA(1c)) level<7%, significantly reduces CV events. The ACCORD trial even
      suggested that under certain circumstances, intensive glucose control is
      associated with an increased risk for CV and all-cause mortality. Although the
      exact mechanisms responsible for an increase in mortality in the ACCORD trial
      remain unknown, there was an association between increased rates of mortality
      with higher rates of severe hypoglycaemia in the intensive glucose control group.
      In contrast, a 10-year post-randomisation follow-up study of the tight glucose
      intervention arm of the UKPDS showed that intensive glucose control was
      associated with a significant reduction in the risk for myocardial infarction
      (MI), diabetes-related deaths and all-cause mortality. This suggests that early
      strict glucose control generates a legacy effect that is eventually translated
      into protection from CV events. Recent meta-analyses of the above randomised
      trails have also shown that intensive glucose control is associated with a
      reduced risk of MI, without a clear benefit on other CV diseases such as stroke.
      Furthermore, these analyses have also shown that intensive glucose control is
      associated with increased rates of severe hypoglycaemia but not increased rates
      of CV or all-cause mortality. Aiming for HbA(1c) levels of <7.0% still remains
      the general target for good glucose control. Under certain circumstances, aiming
      for lower HbA(1c) levels may be appropriate. This applies in the setting of newly
      diagnosed diabetes in relatively young individuals without significant co
      morbidities and in patients treated with agents that minimise the risk of severe
      hypoglycaemia such as metformin. Whether this also applies to newer glucose
      lowering agents that target the incretin system will depend on CV outcomes of
      long-term studies which are in progress.

PMID- 20807682
TI  - Translation and validation of the Malay Acceptance of Cosmetic Surgery Scale.
AB  - The present study examined the psychometric properties of a Malay translation of
      the Acceptance of Cosmetic Surgery Scale (ACSS; Henderson-King & Henderson-King,
      2005). A total of 373 Malaysian women completed the ACSS along with measures of
      ideal-actual weight discrepancy, body appreciation, sociocultural attitudes
      toward appearance, self-esteem, life satisfaction, and demographics. Results
      showed that the Malay ACSS was best reduced to a two-factor solution, although an
      overall score of all 15 ACSS items showed the highest internal consistency.
      Results also showed that this overall score had good discriminant and divergent
      validity. It is expected that the availability of a Malay version of the ACSS
      will stimulate cross-cultural research on the acceptance of cosmetic surgery.

PMID- 20807684
TI  - Explaining the demand for pharmaceuticals in Spain: are there differences in drug
      consumption between foreigners and the Spanish population?
AB  - OBJECTIVE: The aim of this study is to examine the factors driving the demand for
      drugs in Spain, focusing on the existence of disparities in pharmaceutical
      consumption between the Spanish and the foreign population. METHODS: Our analysis
      is based on a multilevel multinomial probit model that compares three consumption
      options (no consumption, prescribed consumption and self-medicated consumption)
      on the five most consumed drugs in Spain. Data is taken from the adult sample of
      the 2006 Spanish National Health Survey, including 29,478 individuals over 15
      years old. RESULTS: Overall, the findings show a lower consumption of medicines
      by some immigrants categories relative to Spaniards. In addition, the results
      indicate that the consumption of medicines is mainly related to variables
      associated to the specific cost sharing structure in Spain, such as health
      limitations and retirement status. Other variables found to explain the demand
      for drugs were: private health insurance, age, sex, alcohol and cigarette
      consumption and drug class. CONCLUSION: Further understanding of the reasons for
      the observed differences in drug consumption on the basis of country of birth
      would allow the health system to design more effective health policies aimed at
      ensuring equality of access to health resources to all population groups.

PMID- 20807685
TI  - Staff attrition among community health workers in home-based care programmes for
      people living with HIV and AIDS in western Kenya.
AB  - OBJECTIVES: This paper examines trends and underlying causes of attrition among
      volunteer community health workers in home-based care for people living with HIV
      and AIDS in western Kenya. METHODS: Ethnographic data were collected between
      January and November 2006 through participant observation, focus group
      discussions and in-depth interviews with 30 CHWs, NGO staff and health care
      providers and 70 PLWHA. RESULTS: An attrition rate of 33% was observed among the
      CHWs. The reasons for dropout included: the cultural environment within which
      CHWs operated; lack of adequate support from area NGOs; poor selection criteria
      for CHWs; and power differences between NGO officials and CHWs which fostered
      lack of transparency in the NGOs' operations. CONCLUSIONS: In order to achieve
      well functioning and sustainable HBC services, factors which influence
      retention/dropout of CHWs should be addressed taking into account the socio
      cultural, programmatic and economic contexts within which CHW activities are
      implemented.

PMID- 20807686
TI  - Capturing the essence of developing endovascular expertise for the construction
      of a global assessment instrument.
AB  - OBJECTIVES: To explore what characterises the development of endovascular
      expertise and to construct a novel global assessment instrument. DESIGN:
      Literature review and an experimental study. MATERIALS AND METHODS: The
      literature was searched for information regarding available global rating scales
      (GRSs); scientific societies' official statements on endovascular competence; and
      task analyses of endovascular procedures. In the experimental study, clinicians
      performed a video-recorded simulated iliac-artery stenting procedure.
      Subsequently, by using the method of retrospective verbalisation, the clinicians
      were interviewed while watching their performance on video commenting on key
      issues of the construct. Data from all sources were analysed, categorised and
      synthesised into a novel rating scale. RESULTS: Available GRSs primarily included
      technical aspects of performance, whereas the competence statements, task
      analyses and clinicians' perceptions added a range of non-technical aspects. The
      novel rating scale SAVE (Structured Assessment of endoVascular Expertise) differs
      from prior scales by including issues of pre-planning; prediction of challenges;
      preparation of tools; management of imaging presentation; distinction of
      technical skills into external and internal control according to operator focus
      of visual attention; adaptation of strategy; clinical decision making; use of
      assistant; complications; inter-personal skills; and post-procedural planning.
      CONCLUSIONS: The essence of developing endovascular expertise goes far beyond
      mere technical aspects.

PMID- 20807689
TI  - [Blood oxygenation level dependent (BOLD)--renal imaging: concepts and
      applications].
AB  - Many renal diseases as well as several pharmacons cause a change in renal blood
      flow and/or renal oxygenation. The blood oxygenation level dependent (BOLD)
      imaging takes advantage of local field inhomogeneities and is based on a T2*
      weighted sequence. BOLD is a non-invasive method allowing an estimation of the
      renal, particularly the medullary oxygenation, and an indirect measurement of
      blood flow without administration of contrast agents. Thus, effects of different
      drugs on the kidney and various renal diseases can be controlled and observed.
      This work will provide an overview of the studies carried out so far and identify
      ways how BOLD can be used in clinical studies.

PMID- 20807690
TI  - [Examination of self-navigating MR-sequences for perfusion imaging of the
      kidneys].
AB  - Due to the worldwide increasing number of cases of chronic kidney diseases renal
      imaging - as a non-invasive technique in magnetic resonance imaging - has become
      a very important tool for an early diagnosis of probable insufficiencies and
      malfunction. Especially, dynamic contrast enhanced magnetic resonance imaging
      (DCE-MRI) provides a technique to derive physiological parameters like renal
      blood flow or glomerular filtration rate. Similar to the entire field of
      abdominal imaging, the major problems are motion artifacts that primarily arise
      from the patient's respiration. The self-navigating BLADE-sequence with a post
      processing motion correction is an approach that does not require breath holding
      and is therefore also easily applicable to patients who are not able to undergo
      multiple breath hold examinations. In this work, a T(1)-weighted BLADE-sequence
      was optimized to demonstrate the feasibility of this technique to perfusion
      imaging. The number of phase-encoding lines of one BLADE has a direct impact on
      the reduction of motion artifacts. In comparison to standard DCE-MRI sequences,
      the developed BLADE-sequence with optimized number of phase encoding lines could
      significantly reduce motion artifacts. A quantitative analysis revealed that up
      to a 50% displacement of the kidneys could be corrected. Therefore, it was
      demonstrated that dynamic motion corrected measurements without the need of a
      breath hold-technique are feasible.

PMID- 20807692
TI  - [Peripherally inserted central catheters (PICC) in onco-hematology. PICC line in
      onco-hematology].
AB  - Peripherally inserted central catheters (PICC) have the advantage of limiting the
      risk of accidents during installation and are easy to remove. Its use in oncology
      remains debated because of possible infectious complications. We analyzed 52 PICC
      in patients with hematological tumor from Nice Hospital. An installation failure
      was noted in 5.8% of cases. After a follow-up of 15 months, the complication rate
      was 26.9%, mainly mechanical complications: obstruction (13.5%) or accidental
      removal (9.6%). The organic complications such as infection or thrombophlebitis
      represented 3.8%. The median duration was 26 days [2-291]. The longest duration
      was associated with PICC for chemotherapy (median: 58 days). Frequent blood
      samples (above: 2 week) were associated with lower duration (median: 23 days). In
      conclusion, PICC represent a simple and effective alternative to intra-venous
      central devices in onco-hematology. However, physicians have to focus on short
      course treatment.

PMID- 20807693
TI  - [Quality insurance system establishment in the management of home-based
      chemotherapy: example of hospital at home "Assistance publique-Hopitaux de
      Paris"].
AB  - While home-based chemotherapy improves comfort and quality of life of patients,
      quality and safety conditions must be equivalent to hospital settings. In
      addition, organization is much more complex. At the hospital at home "Assistance
      publique-Hopitaux de Paris", prescribers are potentially spread across 21 health
      facilities. The administration of chemotherapy is performed by about 300 nurses
      at the patient's home in Paris and its suburbs. Centralized preparations of
      chemotherapy began in September 2009 by the pharmacy department of Georges
      Pompidou European hospital, with a progressive increase of the activity. This
      article describes the quality insurance system established with this new
      organization to meet the specific challenges of home therapy: choice of eligible
      anticancer drugs, computerized information systems and networking with other
      heath facilities, secure transport conditions, traceability from the prescription
      to the administration, security of administration. This experience can offer an
      important support for other centres in their approach of quality insurance for
      home chemotherapy.

PMID- 20807694
TI  - [Surgical oncology of hepatocellular carcinoma (HCC)].
AB  - Incidence of hepatocellular carcinoma (HCC) increases worldwide. 600 new cases
      may occur in Hungary yearly, but statistical data show much fewer patients seen
      in hepatological care units. Despite of new drug sorafenib or ablative
      techniques, surgical methods remain the most effective treatment of HCC. Results
      of orthotropic liver transplantation (OTLX) in selected HCC cases have been
      becoming promising lately. Hungarian transplant capacity and HCC stadium levels
      in the majority of diagnosed cases exclude OTLX for all patients. Surgical
      resection is determined by the functional liver remnant (FLR). Cirrhotic patients
      tolerate left lateral segmentectomy. Tumors of the right lobe after occlusion of
      right main portal branch - if left lobe regeneration is satisfying - might be
      resected even in cirrhotic liver. Intra-operative preconditioning significantly
      diminishes serum levels of ischemia-reperfusion markers and operative risk. At
      the First Department of Surgery of Semmelweis University, 2167 liver tumors were
      operated between 1996 and 2009, including 254 HCC cases. Radical resection was
      performed in 211 (82.7% resection rate). Laparoscopic liver resection is becoming
      popular all over the world, representing less surgical injury compared to open
      procedure. Indication of minimal invasive liver resection is therefore
      specifically important in cirrhotic patients.

PMID- 20807691
TI  - Association of cumulative lead exposure with Parkinson's disease.
AB  - BACKGROUND: Research using reconstructed exposure histories has suggested an
      association between heavy metal exposures, including lead, and Parkinson's
      disease (PD), but the only study that used bone lead, a biomarker of cumulative
      lead exposure, found a nonsignificant increase in risk of PD with increasing bone
      lead. OBJECTIVES: We sought to assess the association between bone lead and PD.
      METHODS: Bone lead concentrations were measured using 109Cd excited K-shell X-ray
      fluorescence from 330 PD patients (216 men, 114 women) and 308 controls (172 men,
      136 women) recruited from four clinics for movement disorders and general
      community cohorts. Adjusted odds ratios (ORs) for PD were calculated using
      logistic regression. RESULTS: The average age of cases and controls at bone lead
      measurement was 67 (SD = 10) and 69 (SD = 9) years of age, respectively. In
      primary analyses of cases and controls recruited from the same groups, compared
      with the lowest quartile of tibia lead, the OR for PD in the highest quartile was
      3.21 [95% confidence interval (CI), 1.17-8.83]. Results were similar but slightly
      weaker in analyses restricted to cases and controls recruited from the movement
      disorders clinics only (fourth-quartile OR = 2.57; 95% CI, 1.11-5.93) or when we
      included controls recruited from sites that did not also contribute cases (fourth
      quartile OR = 1.91; 95% CI, 1.01-3.60). We found no association with patella bone
      lead. CONCLUSIONS: These findings, using an objective biological marker of
      cumulative lead exposure among typical PD patients seen in our movement disorders
      clinics, strengthen the evidence that cumulative exposure to lead increases the
      risk of PD.

PMID- 20807695
TI  - [Subclinical hypothyroidism and the risk for cardiovascular diseases. Are
      epidemiological studies giving the right answers?].
AB  - There is ongoing debate whether subclinical hypothyroidism may exert deleterious
      effects on the cardiovascular system with the consequences of increased morbidity
      and mortality. To elucidate this problem many epidemiological studies have been
      performed, however, these studies have not given an unambiguous answer so far.
      Many confounding elements are influencing the evaluation of these investigations
      which must be taken into consideration. Authors argue for the use of age specific
      reference limits for TSH (especially in older age, where TSH level is often
      shifted to a higher level) to avoid significant misclassification of patients
      with abnormal TSH who may or may not have thyroid dysfunction. Furthermore,
      recent studies have shown that subclinical hypothyroidism is associated with
      increased ischemic heart disease risk, mainly in individuals under the age of 65
      years. In the future, well designed prospective randomized studies with age
      stratified groups and vascular events as the primary endpoint are required and it
      is anticipated that these studies will give the proper answer whether early
      substitution therapy with thyroxin will be able to reverse the ischemic heart
      disease risk in affected patients.

PMID- 20807696
TI  - [Effects of bioactive molecules of Beta vulgaris L. ssp. esculenta var. rubra on
      metastatic prostate cancer].
AB  - Several reports are known about the effects of nutrition supplements in the
      improvement of quality of life of patients with tumor, however, the physiological
      background remains largely unknown. Table beet affects numerous biochemical
      reactions, enzymes and metabolic-synthesis. METHODS: Natural table beet product
      come from commercial service was given twice 10 g daily for 1 month for 24
      patients (mean age 68+/-8 years) with hormone-resistant and metastatic prostate
      cancer treated with taxan chemotherapy, who report themselves first, mean 3,6+/
      2,8 years ago with their complains. 18 men's data were amenable after treatment
      for evaluation. In addition to routine laboratory examination values of HbA1c, 9
      cytokines and levels of 3 growth factors, the global parameters of redox
      homeostasis, few elements of their metal-ions, Zn- and level of free
      protoporfirin, trans-metilating processes before and 1 month after treatment were
      determined. RESULTS: In most of the patients, favorable impact of beet was
      enforced and significantly high levels of Zn- and free protoporfirin decreased;
      furthermore, trans-metilating processes fastened. CONCLUSIONS: According to
      results, it seems that moderate and permanent consumption of table beet product
      affects the life expectancy of patients favorably; however, due to the increasing
      values of EGF, medical control is necessary for patients with prostate cancer
      treated by chemotherapy.

PMID- 20807697
TI  - [Diagnosis and treatment of gastroesophageal reflux at ear-nose-throat outpatient
      care unit and its insurance consequences].
AB  - Gastroesophageal reflux is a frequent, varied disease, which spoils the quality
      of life. It may be present in extraesophageal form, affecting larynx, pharynx,
      upper respiratory tracts, accessory cavities and middle ear. The mass of
      outpatients and the shortage of diagnostic capacities are justifying to make
      diagnosis based on symptoms, and to apply therapy introduced via medical tests.
      Author reports the experiences of 1000 processed cases, and insurance
      consequences are discussed, as well.

PMID- 20807698
TI  - [Drug-eluting balloon in the treatment of a recurrent in-stent restenosis of drug
      eluting stent].
AB  - Although medical treatment of atherosclerotic processes as a cause of the
      coronary artery disease has its own fundamental role, percutaneous coronary
      interventions showed an impressing development due to the intensive innovation.
      The use of stents increased the success rate of percutaneous coronary
      interventions, but in-stent restenosis appeared as a new complication. Drug
      eluting stents are dedicated to decrease the frequency of intima proliferation
      facilitating in-stent restenosis. After implantation of a drug-eluting stent, in
      stent restenosis occurs in less than 10% of the patients. In spite of the
      improving results, in-stent restenosis of a drug-eluting stent has been remained
      unsolved. Besides the biodegradable stents/polymers, drug-eluting balloon may
      indicate the future technology. In this paper a very exciting, educative case is
      presented with a summary of the literature of drug-eluting balloon technique.

PMID- 20807699
TI  - [Infections, chronic diseases: diabetes mellitus, gestational diabetes mellitus
      and bacterial vaginosis].

PMID- 20807701
TI  - T-bet-independent effects of IL-12 family cytokines on regulation of Th17
      responses to experimental T. cruzi infection.
AB  - Tbx21 (i.e., T-bet) is an IFN-gamma-inducible transcription factor that promotes
      Th1 differentiation. Previously, we reported that Tbx21(-/-) mice develop a
      robust Th17 response to the parasite Trypanosoma cruzi, including CD4(+) T cell
      subsets producing IL-17 and IFN-gamma. Because of the known inhibitory effects of
      IFN-gamma on Th17 cells, the purpose of this study was to determine the
      contribution of IFN-gamma to regulation of Th17 differentiation during the course
      of T. cruzi infection. We observed that infection of IFN-gamma(-/-) or Stat-1(-/
      ) mice generated increased numbers of IL-17-producing cells. In sharp contrast to
      infected Stat-1(-/-) or Tbx21(-/-) mice, however, IFN-gamma(-/-) mice developed a
      lower overall Th17 response, suggesting that IFN-gamma was not required for T-bet
      dependent activity, including T-bet-dependent expression of CXCR3. To determine
      if IFN-gamma could influence Th17 responses indirectly by acting on APCs, we
      neutralized IFN-gamma in cultures containing APC and T. cruzi antigens. Although
      anti-IFN-gamma increased IL-17 production modestly, anti-IFN-gamma and anti-IL-12
      led to a significant enhancement of T. cruzi-specific IL-17 (P<0.01). In contrast
      to the inhibitory effects of IL-12, IL-23 was able to stimulate Tbx21(-/-) T
      cells and cause a striking increase in T. cruzi-specific IL-17. These data show
      that the IL-12 family of cytokines can influence Th17 responses in a T-bet
      independent manner and that the effects of IFN-gamma are not necessarily related
      to its ability to induce T-bet expression in T cells.

PMID- 20807704
TI  - Tumor necrosis factor alpha-converting enzyme (TACE/ADAM17) mediates ectodomain
      shedding of the scavenger receptor CD163.
AB  - CD163 is expressed specifically in the monocyte/macrophage lineage, where it
      mediates uptake of haptoglobin-hemoglobin complexes, leading to metabolism of the
      oxidative heme molecule. Shedding of the CD163 ectodomain from the cell surface
      produces a sCD163 plasma protein, and a positive correlation is seen between the
      sCD163 plasma level and the severity of various infectious and inflammatory
      diseases. In the present analysis of the phorbol ester-induced shedding of sCD163
      in CD163 cDNA-transfected HEK293 cells, we used metalloproteinase inhibitors and
      siRNA-mediated inhibition of metalloproteinases to identify TACE/ADAM17 as an
      enzyme responsible for PMA-induced cleavage of the membrane-proximal region of
      CD163. As TACE/ADAM17-mediated shedding of TNF-alpha is up-regulated in
      macrophages subjected to inflammatory stimuli, the present results now provide a
      likely explanation for the strong empirical relationship between the sCD163
      plasma level and infectious/inflammatory diseases relating to macrophage
      activity.

PMID- 20807703
TI  - Protective effects of apocynin, an inhibitor of NADPH oxidase activity, in
      splanchnic artery occlusion and reperfusion.
AB  - SAO shock is a severe form of circulatory shock produced by I/R of the splanchnic
      organs. SAO causes an enhanced formation of ROS, which contributes to the
      pathophysiology of shock. Apocynin is a naturally occurring, methoxy-substituted
      catechol, experimentally used as an inhibitor of NOX. It can decrease the
      production of ROS from activated neutrophils and macrophages, inhibiting the
      assembly of NADPH-oxidase activity. In this study, we wanted to evaluate the
      pharmacological action of apocynin in rats subjected to SAO shock, which was
      induced by clamping the superior mesenteric artery and the celiac trunk,
      resulting in a total occlusion of these arteries for 45 min. After this period of
      occlusion, the clamps were removed. Administration of apocynin i.p. (5 mg/kg i.p.
      10% DMSO) 5 min before reperfusion significantly reduced the (1) histological
      evidence of tissue injury, (2) proinflammatory cytokine production (TNF-alpha, IL
      1beta), (3) adhesion molecules (ICAM-1, P-selectin), (4) nitrotyrosine formation,
      (5) NF-kappaB expression, and (6) apoptosis (Bax, Bcl-2, Fas-L, and TUNEL). These
      results could imply a future use of apocynin in the treatment of I/R shock.

PMID- 20807705
TI  - Arsenic modulates APOBEC3G-mediated restriction to HIV-1 infection in myeloid
      dendritic cells.
AB  - DC are major targets of HIV-1 during the early events of infection. Yet, HIV-1
      infects these cells only inefficiently in vitro as compared with CD4+T
      lymphocytes. Accordingly, we have previously identified a strong post-entry block
      to HIV-1 replication in MDDC as a result of the cellular restriction factor A3G.
      Furthermore, we have demonstrated that As2O3, a drug used to treat acute
      promyelocytic leukemia, can fully eliminate the potent post-entry restriction of
      HIV-1 infection in MDDC and in blood-derived MyDC by mechanisms that were
      unclear. We are now exploring the interplay between As2O3 and A3G-mediated
      restriction in primary DC subsets. Here, we report that As2O3 counteracts A3G
      mediated restriction in MyDC but not in MDDC. RNAi of A3G in MyDC indicated that
      the As2O3-mediated increase of HIV-1 infection was largely dependent on the
      presence of the cellular restriction factor. This study reveals an unexpected
      interplay between As2O3 and A3G-mediated restriction to HIV-1 infection in
      primary human MyDC.

PMID- 20807702
TI  - TRAIL-expressing CD8+ T cells mediate tolerance following soluble peptide-induced
      peripheral T cell deletion.
AB  - Peripheral tolerance controls the action of self-reactive T cells that escape
      thymic deletion. We showed previously that deletion of Ag-specific CD4+ T cells
      induced a CD8+ T(reg) population that maintained tolerance by deleting T cells
      with the same Ag specificity. The present study explored the mechanism of action
      of these CD8+ T(reg). Following OT-II T cell deletion by soluble OVA323-339, B6
      mice were unresponsive to challenge after CFA/OVA immunization, and Trail-/- or
      Dr5-/- mice were immune, although all strains displayed similar OT-II peripheral
      deletion. Interestingly, B6 mice remained tolerant to OVA even after a second
      infusion of OT-II T cells. Tolerance could be transferred to naive recipients
      using CD8+ T cells from B6 or Dr5-/- mice that experienced peptide-induced
      peripheral OT-II deletion but not from Trail-/- mice. Subsequent investigation
      found that the mechanism of action of the CD8+ T(reg) was TRAIL-mediated OT-II T
      cell deletion in a TCR-specific manner. Furthermore, the tolerance was transient,
      as it was established by 14 days after peptide injection but lost by Day 56.
      Together, these data provide evidence to suggest that the mechanism behind
      transient peripheral tolerance induced following T cell deletion is the cytotoxic
      activity of TRAIL-expressing CD8+ T(reg).

PMID- 20807706
TI  - The regulatory role of nitric oxide in proinflammatory cytokine expression during
      the induction and resolution of inflammation.
AB  - Upon inflammation, neutrophils and subsequently monocytes infiltrate into the
      involved site. Neutrophils perform functions such as bacterial killing or tissue
      destruction and then undergo apoptosis, whereas monocytes differentiate into
      macrophages at the site. Macrophages and other phagocytes finally clear apoptotic
      neutrophils, leading to resolution of the inflammation. One of the key steps
      during inflammation is leukocyte infiltration, which is controlled chiefly by
      chemokines for neutrophils and monocytes. The production of these chemokines is
      regulated positively or negatively by iNOS-derived NO. Although the mechanisms
      underlying such dual effects of NO remain unknown, the level of NO and duration
      of NO exposure appear to be determining factors. The clearance of apoptotic
      neutrophils without causing further proinflammatory responses, on the other hand,
      is another key event during inflammation. The production of proinflammatory
      cytokines appears to be actively suppressed by TGF-beta and NO, which are
      produced by phagocytes upon interaction with apoptotic cells. Overall, NO plays a
      critical role during inflammation and therefore, remains a potential target for
      developing therapeutics for inflammatory diseases.

PMID- 20807707
TI  - Endogenous PGE2 promotes the induction of human Th17 responses by fungal beta
      glucan.
AB  - The interaction of PAMPs with cells of the innate immune system shapes the
      adaptive host response. Here, we report that beta-glucan, a major fungal PAMP
      purified from Candida albicans, stimulates human DCs to secrete a pro-Th17
      cytokine pattern. Notably, beta-glucan induces PGE2 production, which has been
      shown to play a pivotal role in Th17 cell expansion. Inhibition of PGE2 synthesis
      or blockade of PGE2 receptors EP2 and EP4 drastically reduces IL-23 production by
      beta-glucan-activated DCs, suggesting that endogenous PGE2 amplifies IL-23
      synthesis in response to the C. albicans PAMP. Moreover beta-glucan promotes the
      expansion of Th17 cells, which is strongly decreased by EP2 and EP4 receptor
      blockade on DCs. Our results highlight a novel role for PGE2 in the regulation of
      innate and adaptive immune response triggered by recognition of a prominent,
      highly conserved fungal PAMP such as beta-glucan.

PMID- 20807708
TI  - Rapid detection of Acanthamoeba cysts in frozen sections of corneal scrapings
      with Fungiflora Y.

PMID- 20807710
TI  - The chemistry of retinal transplantation: the influence of polymer scaffold
      properties on retinal cell adhesion and control.
AB  - Age-related macular degeneration is the most common cause of blindness in the UK.
      Cellular replacement of retinal pigment epithelium cells is a potential
      therapeutic option to treat the cellular loss and dysfunction which is
      characteristic of age-related macular degeneration and other progressive
      retinopathies. A supportive scaffold, natural or artificial, may be required to
      facilitate cell delivery to the eye. Research to improve the biomimetic
      properties of such scaffolds, in order to optimise cell attachment and
      functionality following implantation, is ongoing. This short review will focus on
      the potential of biomaterials for ocular tissue engineering and how surface
      modification and the physical properties of these scaffolds can be tailored to
      help realise the full clinical potential of retinal pigment epithelium cell
      transplantation.

PMID- 20807709
TI  - Cataract and cognitive impairment: a review of the literature.
AB  - Acquired cataract and cognitive impairment are both common age-related problems,
      and ophthalmologists are increasingly likely to encounter patients who have both.
      Patients with dementia types who display early visuoperceptual impairment may
      present first to ophthalmology services. When these patients have coexisting
      cataract, it may be difficult to distinguish visual complaints due to cataract
      from those due to dementia. The interaction between visual impairment due to
      cataract and neurodegenerative disorders affecting the central visual pathways,
      is not fully understood. Visual impairment due to cataract may stress impaired
      attentional mechanisms and cataract extraction may improve cognitive performance
      in some patients with early cognitive impairment; however, the benefits of
      cataract surgery in established dementia are less clear. In this study, the
      literature on this subject was reviewed and the implications for practice were
      considered.

PMID- 20807711
TI  - WHO international cytokine standards and reference preparations.

PMID- 20807712
TI  - Genital epithelial cells: foot soldiers or fashion leaders?

PMID- 20807713
TI  - Heat shock proteins: Darwinistic immune modulation on dangerous grounds.

PMID- 20807715
TI  - Filter the dogs: microbial mishaps in Massachusetts.

PMID- 20807714
TI  - TNF-alpha impairs regulation of muscle oxidative phenotype: implications for
      cachexia?
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by weight loss,
      muscle wasting (in advanced disease ultimately resulting in cachexia), and loss
      of muscle oxidative phenotype (oxphen). This study investigates the effect of
      inflammation (as a determinant of muscle wasting) on muscle oxphen by using cell
      studies combined with analyses of muscle biopsies of patients with COPD and
      control participants. We analyzed markers (citrate synthase, beta-hydroxyacyl-CoA
      dehydrogenase, and cytochrome c oxidase IV) and regulators (PGC-1alpha, PPAR
      alpha, and Tfam) of oxphen in vastus lateralis muscle biopsies of patients with
      advanced COPD and healthy smoking control participants. Here 17 of 73 patients
      exhibited elevated muscle TNF-alpha mRNA levels. In these patients, significantly
      lower mRNA levels of all oxidative markers/regulators were found. Interestingly,
      these patients also had a significantly lower body mass index and tended to have
      less muscle mass. In cultured muscle cells, mitochondrial protein content and
      myosin heavy chain isoform I (but not II) protein and mRNA levels were reduced on
      chronic TNF-alpha stimulation. TNF-alpha also reduced mitochondrial respiration
      in a nuclear factor kappaB (NF-kappaB) -dependent manner. Importantly, TNF-alpha
      induced NF-kappaB activation decreased promoter transactivation and
      transcriptional activity of regulators of mitochondrial biogenesis and muscle
      oxphen. In conclusion, these results demonstrate that TNF-alpha impairs muscle
      oxphen in a NF-kappaB-dependent manner.

PMID- 20807716
TI  - What price for an extra-ordinary commodity?

PMID- 20807717
TI  - Bone mineral density, bone turnover markers and cytokines in alcohol-induced
      cirrhosis.
AB  - AIMS: Liver cirrhosis is a risk factor for osteoporosis. However, the
      pathogenesis of the bone mass loss in patients with alcohol-induced cirrhosis
      (AC) is not well understood. Serum concentrations of soluble tumour necrosis
      factor receptor (sTNF-R55), neopterin and soluble interleukin 2 receptor (sIL
      2R), activation markers of cellular immunity, correlate with clinical activity
      and severity of the AC. The aim of this study is to evaluate the association of
      these soluble markers with the development of osteoporosis in patients with AC.
      METHODS: We studied 33 consecutive patients with AC and 24 healthy volunteers.
      Bone mineral density (BMD) was measured by X-ray absorptiometry in the lumbar
      spine (LS) and femoral neck (FN). Neopterin was measured by radioimmunoassay.
      Serum concentrations of sTNF-R55 and sIL-2R were measured by enzyme immunoassay.
      We also determined serum levels of osteocalcin and bone alkaline phosphatase as
      biochemical markers of bone formation, and deoxypyridinoline urinary excretion (D
      Pyr) as marker of bone resorption. RESULTS: Patients with AC had reduced BMD
      (expressed as z-score) in all sites (LS: P < 0.001 and FN: P < 0.05). Serum
      concentrations of sTNF-R55 were significantly higher in patients with both AC and
      osteoporosis than in those with only AC (P < 0.001). Serum levels of sTNF-R55
      positively correlated with D-Pyr urinary excretion (r = 0.354; P = 0.01). Serum
      levels of sIL-2R were significantly higher in patients with both AC and
      osteoporosis than in those with only AC (P < 0.05). CONCLUSIONS: There is a
      relation between activation of the cellular immunity and osteoporosis in AC. Bone
      mass loss could be related to the increased bone resorption found in these
      patients.

PMID- 20807718
TI  - Behavioural observations of singly-housed grey short-tailed opossums (Monodelphis
      domestica) in standard and enriched environments.
AB  - The grey short-tailed opossum (Monodelphis domestica) has been used in biomedical
      research for over three decades. It is normally housed in standard rat cages and
      appears to have adapted well to captivity. Owing to their aggressive behaviour
      towards each other, adult males are normally housed singly and may spend
      considerable periods of time in social isolation. We wanted to carry out a
      preliminary study on the behaviour of singly-housed male short-tailed opossums in
      two different settings: a standard rat cage and an enriched floor pen. Five male
      opossums aged between 10 and 12 weeks were housed for seven days at a time in the
      two settings and their behaviour was filmed during the dark phase. Recordings
      were carried out on the first and the last night of housing, from 19:00 to 07:00
      h, and all behaviours quantified according to an ethogram. All five males in this
      study showed stereotypic behaviours while housed in standard rat cages, but no
      such behaviours were seen when the animals were in the floor pen. In both cases,
      but very especially in the pen, animals spent less time active as the week came
      to an end. Some activities such as sniffing the air, manipulating the nest and,
      especially, interacting with the floor tube occupied the animals' time in the
      cage considerably more than in the pen. Conversely, the opossums spent
      considerably more time walking when inside the floor pen than when they were in
      the cage. The general trend with other activities such as eating, drinking or
      grooming was one of more time being devoted to them inside the cage than inside
      the floor pen, but the differences did not approach statistical significance.
      These findings suggest that single housing of short-tailed opossums in standard
      rat caging is detrimental to their welfare.

PMID- 20807719
TI  - Proximal row carpectomy for scapholunate dissociation.
AB  - Thirty-one patients underwent proximal row carpectomy for static scapholunate
      dissociation without degenerative arthritis. We report the radiographic and
      clinical results including wrist range of motion, grip strength, use of pain
      medication, pain severity and patient satisfaction. Mean postoperative
      flexion/extension was 74 degrees  (range 5 degrees -150 degrees ) compared with
      137 degrees  (range 70 degrees -175 degrees ) for the uninvolved side. Mean grip
      strength was 22 kg for the involved side and 39 kg for uninvolved side. Fifteen
      of 31 patients reported moderate or severe pain after proximal row carpectomy,
      requiring wrist arthrodesis in four patients. Nearly half of patients involved in
      manual labour did not return to their pre-injury work status. Our findings
      suggest that proximal row carpectomy, when performed for static scapholunate
      dissociation, results in a stiffened, weakened wrist. When compared to historic
      series involving other treatments for scapholunate dissociation, patients are
      less likely to return to pre-injury occupation and have subjective and objective
      parameters that are below normally expected values after proximal row carpectomy
      performed for other conditions.

PMID- 20807720
TI  - Flexor tendon repair in zone III.
AB  - There is a paucity of the literature on the outcome of zone III flexor tendon
      injuries. In this paper, we report on the results of zone III flexor tendon
      repair in 35 consecutive adult patients with clean cut lacerations of both flexor
      tendons in 42 fingers. There were 25 men and 10 women with an average age of 32
      years. Repair of both flexor tendons was performed using 'figure of eight' core
      sutures and a continuous epitendinous suture. Postoperatively, an immediate
      active range of motion protocol was applied to ensure full active extension of
      the interphalangeal joints. The results were assessed using the Strickland
      Glogovac grading system. There were no ruptures. One patient with two injured
      fingers developed complex regional pain syndrome and the final outcome was fair
      in both fingers. In the remaining 34 patients (40 fingers), 33 patients (38
      fingers) had an excellent outcome and the remaining patient (two fingers) had a
      good outcome.

PMID- 20807721
TI  - Long-term outcomes of osseointegrated digital prostheses for proximal
      amputations.
AB  - This paper presents outcomes after 13, 4, and 3&frac12; years in three digital
      amputees treated with osseointegrated prostheses. One had prosthetic replacement
      of the index and middle fingers at the PIP level. The second had four fingers
      replaced at the PIP level, but only three prostheses were retained. The third had
      a thumb replacement at the MCP level. All patients scored their reconstructed
      hand highly in terms of appearance and frequency of use. The first and third
      patients rated the function of the reconstructed hand as similar to the normal
      hand, and this was confirmed by the Jebsen Test, but the second patient had poor
      function. All patients could detect pressure and vibration through their
      prostheses, although grip and pinch strengths were weaker in all three. All three
      also experienced some pain in the implanted fingers. This study identifies
      osseointegration as a stable long-term reconstructive option.

PMID- 20807722
TI  - Method of bacterial killing differentially affects the human innate immune
      response to Staphylococcus epidermidis.
AB  - BACKGROUND: In vitro investigations of human innate immune responses to
      extracellular bacteria commonly utilise killed preparations in preference to live
      organisms. The effects of the bacterial preparation method on the activation of
      innate signalling pathways by the common opportunistic pathogen Staphylococcus
      epidermidis (SE) are unknown. MATERIALS AND METHODS: Mononuclear cell cytokine
      expression patterns induced by live (LSE), heat-killed (HKSE) and ethanol-killed
      SE (EKSE) were characterized at the transcriptional and translational level. Toll
      like receptor (TLR)-activating capacity of the preparations was analysed using
      TLR-transfected human embryonic kidney cells. RESULTS: Live SE activated NF
      kappaB, STAT1, type I interferon, and inflammasome pathways. Killed preparations
      engaged the NF-kappaB pathway, but had significantly lower capacity to activate
      other innate immune pathways. CONCLUSIONS: Killing of extracellular bacteria has
      significant qualitative and quantitative effects on key aspects of innate
      responses in vitro. Interpretation of in vitro data and extrapolation of findings
      should take into account the potential effects of bacterial preparation and
      should not assume that responses to killed bacteria are predictive of responses
      to live organisms.

PMID- 20807723
TI  - Sensitivities of mRNA expression levels of Kiss1 and its receptor, Kiss1r, to
      nutritional status are changed during the developmental period in female rats.
AB  - Decreased activity of kisspeptin, the product of the hypothalamic Kiss1 gene, is
      the major cause of the suppression of reproductive function in subnutritional
      conditions. The sensitivities of the endocrine and the hypothalamic neuronal
      systems to nutritional status develop during the neonatal period. We examined the
      developmental changes in the sensitivity of hypothalamic mRNA expression of Kiss1
      and its receptor, Kiss1r, to nutritional status in female rats. Kiss1 mRNA
      expression was reduced by 24 h food deprivation (24 h FD) at postnatal day 25,
      but not at postnatal day 5 or 15. Kiss1r mRNA expression was reduced by the 12 or
      24 h FD at postnatal days 5 and 25, but not at postnatal day 15. Kiss1r mRNA
      level was found to be correlated with the plasma leptin level, and the
      administration of leptin, which increased the serum leptin concentration above
      the physiological range, restored the acute FD-induced suppression of Kiss1r mRNA
      expression. These data suggest that the hypothalamic Kiss1 and Kiss1r mRNA
      expression is differentially affected by the nutritional condition at different
      age points. It is speculated that the sensitivity of Kiss1 mRNA, which is
      expressed in kisspeptin neuron, to nutritional status develops during the
      neonatal period. On the other hand, it seems that the sensitivity of Kiss1r mRNA,
      which is expressed in GnRH neuron, to nutritional status has been already
      established during the early neonatal period. These data also show that
      hypoleptinemia plays a role in the reduction of hypothalamic Kiss1r mRNA
      expression under subnutritional conditions.

PMID- 20807724
TI  - Evidence for expression of relaxin hormone-receptor system in the boar testis.
AB  - Although the physiological role of relaxin (RLN) in males remains largely
      unknown, there is limited evidence that the testis might be a candidate source
      and target of RLN in boars, as RLN transcripts are detected in the boar testis
      and it contains RLN-binding sites. To determine whether the boar testis acts as a
      source and target tissue of RLN, we characterised the expression pattern and
      cellular localisation of both RLN and its own receptor LGR7 (RXFP1) in boar
      testes during postnatal development by molecular and immunological approaches.
      Testes were collected from Duroc boars, and partial cDNA sequences of the boar
      homologue of human RXFP1 were identified. RLN expression increased through
      puberty onwards, while RXFP1 expression changed little during development. RLN
      mRNA and protein expression were restricted to the Leydig cells, whereas both
      Leydig cells and seminiferous epithelial cells expressed RXFP1 mRNA and protein.
      Interestingly, RLN was expressed in the testis as an 18 kDa form (the expected
      size of proRLN), but not as the 6 kDa mature form, during development because of
      a lack of the enzyme required for proRLN processing. In contrast, RXFP1 was
      detected at all stages as specific bands of 75 and 91-95 kDa (likely non
      glycosylated and glycosylated RXFP1 respectively). Thus, we provide evidence for
      expression of RLN-RXFP1 ligand-receptor system in the boar testis, suggesting
      that the testis act as a source and possible target tissue of RLN.

PMID- 20807726
TI  - Skeletal sexual dimorphism: relative contribution of sex steroids, GH-IGF1, and
      mechanical loading.
AB  - Structural gender differences in bone mass - characterized by wider but not
      thicker bones - are generally attributed to opposing sex steroid actions in men
      and women. Recent findings have redefined the traditional concept of sex hormones
      as the main regulators of skeletal sexual dimorphism. GH-IGF1 action is likely to
      be the most important determinant of sex differences in bone mass. Estrogens
      limit periosteal bone expansion but stimulate endosteal bone apposition in
      females, whereas androgens stimulate radial bone expansion in males. Androgens
      not only act directly on bone through the androgen receptor (AR) but also
      activate estrogen receptor-alpha or -beta (ERalpha or ERbeta) following
      aromatization into estrogens. Both the AR and ERalpha pathways are needed to
      optimize radial cortical bone expansion, whereas AR signaling alone is the
      dominant pathway for normal male trabecular bone development. Estrogen/ERalpha
      mediated effects in males may - at least partly - depend on interaction with
      IGF1. In addition, sex hormones and their receptors have an impact on the
      mechanical sensitivity of the growing skeleton. AR and ERbeta signaling may limit
      the osteogenic response to loading in males and females respectively, while
      ERalpha may stimulate the response of bone to mechanical stimulation in the
      female skeleton. Overall, current evidence suggests that skeletal sexual
      dimorphism is not just the end result of differences in sex steroid secretion
      between the sexes, but depends on gender differences in GH-IGF1 and mechanical
      sensitivity to loading as well.

PMID- 20807725
TI  - In vitro expression of NGN3 identifies RAB3B as the predominant Ras-associated
      GTP-binding protein 3 family member in human islets.
AB  - Neurogenin 3 (NGN3) commits pancreatic progenitors to an islet cell fate. We have
      induced NGN3 expression and identified upregulation of the gene encoding the Ras
      associated small molecular mass GTP-binding protein, RAB3B. RAB3B localised to
      the cytoplasm of human beta-cells, both during the foetal period and post
      natally. Genes encoding alternative RAB3 proteins and RAB27A were unaltered by
      NGN3 expression and in human adult islets their transcripts were many fold less
      prevalent than those of RAB3B. The regulation of insulin exocytosis in rodent
      beta-cells and responsiveness to incretins are reliant on Rab family members,
      notably Rab3a and Rab27a, but not Rab3b. Our results support an important inter
      species difference in regulating insulin exocytosis where RAB3B is the most
      expressed isoform in human islets.

PMID- 20807727
TI  - Peroxiredoxin III protects pancreatic beta cells from apoptosis.
AB  - Type 1 diabetes mellitus is characterized by a progressive autoimmune destruction
      of insulin-producing beta cells. Macrophages and T lymphocytes release cytokines,
      which induce the synthesis of oxygen and nitrogen radicals in the pancreatic
      islets. The resulting cellular and mitochondrial damage promotes beta cell death.
      beta cells are very sensitive to the autoimmune free radical-dependent attack due
      to their low content of antioxidant enzymes such as glutathione peroxidase and
      catalase. A focal point of beta cell protection should be the control of the
      mitochondrial redox status, which will result in the preservation of metabolic
      stimulus-secretion coupling. For this reason, there is a considerable interest in
      the mitochondrial peroxiredoxin III (PRX III), a thioredoxin-dependent peroxide
      reductase, which was shown to be able to protect against both oxidative and
      nitrosative stress. Using the Tet-On-system, we generated stably transfected rat
      insulinoma cells over- or under-expressing PRX III in a doxycyclin-dependent
      manner to analyze the effect of increased or decreased amounts of cellular PRX
      III, following treatment with several stressors. We provide evidence that PRX III
      protects pancreatic beta cells from cell stress induced by accumulation of
      hydrogen peroxide, or the induction of inducible nitric oxide synthase or caspase
      9 and -3 by pro-inflammatory cytokines or streptozotocin. Basal insulin secretion
      was markedly decreased in cells expressing lower levels of PRX III. We suggest
      PRX III may be a suitable target for promoting deceleration or even prevention of
      stress-associated apoptosis in pancreatic beta cells and the manifestation of
      insulin-dependent diabetes mellitus.

PMID- 20807730
TI  - Hallmarks of opium poisoning in infants and toddlers.
AB  - Accidental opium intoxication in children is an extremely dangerous poisoning if
      it remains undiagnosed and untreated. The classic triad of miosis, decreased
      level of consciousness and bradypnea, which are the hallmarks of opiate
      intoxication, are used for the diagnosis of opium poisoning in adults and
      children. Little attention has been paid to the signs of opium intoxication in
      children and no published study has explored the frequency of hallmarks of this
      type of poisoning in the paediatric population. We conducted a study in order to
      evaluate the prevalence of major signs of opium poisoning in infants and
      toddlers. In this study, a total of 228 infants and 82 toddlers who had been
      admitted to Loghman Hakim Hospital as a result of opium poisoning between 2001
      and 2009 were evaluated, retrospectively. The most usual sign of opium poisoning
      was miosis (90%) followed by a decreased level of consciousness (88.4%),
      bradypnea (28.4%) and seizure (10.3%). The prevalence of the triad of miosis,
      bradypnea and a decreased level of consciousness was 25.2%. Miosis in association
      with decreased level of consciousness was detected in 82.6% of our patients.
      Bradypnea was present in 74 infants and 14 toddlers, which shows a statistically
      significant difference (P = 0.01). The mean age and weight of the patients with
      bradypnea were significantly less than those without bradypnea (P = 0.008 and P =
      0.0001, respectively). Bradypnea and seizure were significantly more common in
      females (36.7% versus 26%; P = 0.05 and 15.2% versus 6.5%; P = 0.01,
      respectively). Miosis in association with a decreased level of consciousness is
      the most useful indicator of opium poisoning in infants and toddlers.
      Furthermore, seizure is a more common feature of this type of poisoning in
      infants, especially in those who are less than 1 month old.

PMID- 20807731
TI  - Opioid induced hypogonadism.

PMID- 20807732
TI  - NHS franchise for sale.

PMID- 20807733
TI  - NICE is likely to reject bevacizumab for bowel cancer.

PMID- 20807737
TI  - External validity of risk models: Use of benchmark values to disentangle a case
      mix effect from incorrect coefficients.
AB  - Various performance measures related to calibration and discrimination are
      available for the assessment of risk models. When the validity of a risk model is
      assessed in a new population, estimates of the model's performance can be
      influenced in several ways. The regression coefficients can be incorrect, which
      indeed results in an invalid model. However, the distribution of patient
      characteristics (case mix) may also influence the performance of the model. Here
      the authors consider a number of typical situations that can be encountered in
      external validation studies. Theoretical relations between differences in
      development and validation samples and performance measures are studied by
      simulation. Benchmark values for the performance measures are proposed to
      disentangle a case-mix effect from incorrect regression coefficients, when
      interpreting the model's estimated performance in validation samples. The authors
      demonstrate the use of the benchmark values using data on traumatic brain injury
      obtained from the International Tirilazad Trial and the North American Tirilazad
      Trial (1991-1994).

PMID- 20807738
TI  - Childhood acute leukemia, early common infections, and allergy: The ESCALE Study.
AB  - This study investigated the role of factors considered related to early
      stimulation of the immune system in the etiology of childhood acute leukemia. The
      national registry-based case-control study ESCALE was carried out in France in
      2003-2004. Population controls were frequency matched to cases on age and gender.
      Data were obtained from structured telephone questionnaires administered to
      mothers. Odds ratios were estimated using unconditional regression models
      adjusted for potential confounders. Included were 634 acute lymphoblastic
      leukemia cases, 86 acute myeloblastic leukemia cases, and 1,494 controls aged >=1
      year. Negative associations were observed between acute lymphoblastic leukemia
      and birth order (P for trend < 0.0001), attendance at a day-care center before
      age 1 year (odds ratio (OR) = 0.8, 95% confidence interval (CI): 0.6, 1.1),
      prolonged breastfeeding (OR = 0.7, 95% CI: 0.5, 1.0), repeated early common
      infections (OR = 0.7, 95% CI: 0.6, 0.9), regular contact with farm animals (OR =
      0.6, 95% CI: 0.5, 0.8), frequent farm visits in early life (OR = 0.4, 95% CI:
      0.3, 0.6), and history of asthma (OR = 0.7, 95% CI: 0.4, 1.0) or eczema (OR =
      0.7, 95% CI: 0.6, 0.9). Results support the hypothesis that repeated early
      infections and asthma may play a role against childhood acute leukemia.

PMID- 20807736
TI  - Early blood gas abnormalities and the preterm brain.
AB  - The authors explored associations between blood gas abnormalities in more than
      1,000 preterm infants during the first postnatal days and indicators of neonatal
      brain damage. During 2002-2004, women delivering infants before 28 weeks'
      gestation at one of 14 participating institutions in 5 US states were asked to
      enroll in the study. The authors compared infants with blood gas values in the
      highest or lowest quintile for gestational age and postnatal day (extreme value)
      on at least 1 of the first 3 postnatal days with the remainder of the subjects,
      with separate analyses for blood gas abnormalities on multiple days and for
      partial pressure of oxygen in the alveolar gas of <35. Outcomes analyzed were
      ventriculomegaly and an echolucent lesion on an ultrasound scan in the neonatal
      intensive care unit, and cerebral palsy, microcephaly, and a low score on a
      Bayley Scale of Infant Development at 24 months. Every blood gas derangement
      (hypoxemia, hyperoxemia, hypocapnia, hypercapnia, and acidosis) was associated
      with multiple indicators of brain damage. However, for some, the associations
      were seen with only 1 day of exposure; others were evident with 2 or more days'
      exposure. Findings suggest that individual blood gas derangements do not increase
      brain damage risk. Rather, the multiple derangements associated with indicators
      of brain damage might be indicators of immaturity/vulnerability and illness
      severity.

PMID- 20807740
TI  - Neuroprotection and brain cholesterol biosynthesis in Huntington's disease.

PMID- 20807742
TI  - H2-O, a MHC class II-like protein, sets a threshold for B-cell entry into
      germinal centers.
AB  - Upon antigen (Ag) encounter, B cells require T-cell help to enter the germinal
      center (GC). They obtain this help by presenting Ag-derived peptides on MHC class
      II (MHCII) for recognition by the T-cell receptor (TCR) of CD4(+) T cells.
      Peptides are loaded onto MHCII in endosomal compartments in a process catalyzed
      by the MHCII-like protein H2-M (HLA-DM in humans). This process is modulated by
      another MHCII-like protein, H2-O (HLA-DO in humans). H2-O is a biochemical
      inhibitor of peptide loading onto MHCII; however, on the cellular level, it has
      been shown to have varying effects on Ag presentation. Thus, the function of H2-O
      in the adaptive immune response remains unclear. Here, we examine the effect of
      H2-O expression on the ability of Ag-specific B cells to enter the GC. We show
      that when Ag specific WT and H2-O(-/-) B cells are placed in direct competition,
      H2-O(-/-) B cells preferentially populate the GC. This advantage is confined to
      Ag-specific B cells and is due to their superior ability to obtain Ag-specific T
      cell help when T-cell help is limiting. Overall, our work shows that H2-O
      expression reduces the ability of B cells to gain T-cell help and participate in
      the GC reaction.

PMID- 20807743
TI  - Advanced hardware and software tools for fast multidimensional imaging of living
      cells.

PMID- 20807744
TI  - Microbial community transcriptomes reveal microbes and metabolic pathways
      associated with dissolved organic matter turnover in the sea.
AB  - Marine dissolved organic matter (DOM) contains as much carbon as the Earth's
      atmosphere, and represents a critical component of the global carbon cycle. To
      better define microbial processes and activities associated with marine DOM
      cycling, we analyzed genomic and transcriptional responses of microbial
      communities to high-molecular-weight DOM (HMWDOM) addition. The cell density in
      the unamended control remained constant, with very few transcript categories
      exhibiting significant differences over time. In contrast, the DOM-amended
      microcosm doubled in cell numbers over 27 h, and a variety of HMWDOM-stimulated
      transcripts from different taxa were observed at all time points measured
      relative to the control. Transcripts significantly enriched in the HMWDOM
      treatment included those associated with two-component sensor systems, phosphate
      and nitrogen assimilation, chemotaxis, and motility. Transcripts from Idiomarina
      and Alteromonas spp., the most highly represented taxa at the early time points,
      included those encoding TonB-associated transporters, nitrogen assimilation
      genes, fatty acid catabolism genes, and TCA cycle enzymes. At the final time
      point, Methylophaga rRNA and non-rRNA transcripts dominated the HMWDOM-amended
      microcosm, and included gene transcripts associated with both assimilatory and
      dissimilatory single-carbon compound utilization. The data indicated specific
      resource partitioning of DOM by different bacterial species, which results in a
      temporal succession of taxa, metabolic pathways, and chemical transformations
      associated with HMWDOM turnover. These findings suggest that coordinated,
      cooperative activities of a variety of bacterial "specialists" may be critical in
      the cycling of marine DOM, emphasizing the importance of microbial community
      dynamics in the global carbon cycle.

PMID- 20807745
TI  - VIVID interacts with the WHITE COLLAR complex and FREQUENCY-interacting RNA
      helicase to alter light and clock responses in Neurospora.
AB  - The photoreceptor and PAS/LOV protein VIVID (VVD) modulates blue-light signaling
      and influences light and temperature responses of the circadian clock in
      Neurospora crassa. One of the main actions of VVD on the circadian clock is to
      influence circadian clock phase by regulating levels of the transcripts encoded
      by the central clock gene frequency (frq). How this regulation is achieved is
      unknown. Here we show that VVD interacts with complexes central for circadian
      clock and blue-light signaling, namely the WHITE-COLLAR complex (WCC) and
      FREQUENCY-interacting RNA helicase (FRH), a component that complexes with FRQ to
      mediate negative feedback control in Neurospora. VVD interacts with FRH in the
      absence of WCC and FRQ but does not seem to control the exosome-mediated negative
      feedback loop. Instead, VVD acts to modulate the transcriptional activity of the
      WCC.

PMID- 20807747
TI  - Phonological decisions require both the left and right supramarginal gyri.
AB  - Recent functional imaging studies demonstrated that both the left and right
      supramarginal gyri (SMG) are activated when healthy right-handed subjects make
      phonological word decisions. However, lesion studies typically report
      difficulties with phonological processing after left rather than right hemisphere
      damage. Here, we used a unique dual-site transcranial magnetic stimulation (TMS)
      approach to test whether the SMG in the right hemisphere contributes to modality
      independent (i.e., auditory and visual) phonological decisions. To test task
      specificity, we compared the effect of real or sham TMS during phonological,
      semantic, and perceptual decisions. To test laterality and anatomical
      specificity, we compared the effect of TMS over the left, right, or bilateral SMG
      and angular gyri. The accuracy and reaction times of phonological decisions were
      selectively disrupted relative to semantic and perceptual decisions when real TMS
      was applied over the left, right, or bilateral SMG. These effects were not
      observed for TMS over the angular gyri. A follow-up experiment indicated that the
      threshold-intensity for inducing a disruptive effect on phonological decisions
      was identical for unilateral TMS over the right or left SMG. Taken together,
      these findings provide converging evidence that the right SMG contributes to
      accurate and efficient phonological decisions in the healthy brain, with no
      evidence that the left and right SMG can compensate for one another during TMS.
      Our findings motivate detailed studies of phonological processing in patients
      with acute or long-term damage of the right SMG.

PMID- 20807749
TI  - Narrowing the US energy efficiency gap.

PMID- 20807748
TI  - A regulatory toolbox of MiniPromoters to drive selective expression in the brain.
AB  - The Pleiades Promoter Project integrates genomewide bioinformatics with large
      scale knockin mouse production and histological examination of expression
      patterns to develop MiniPromoters and related tools designed to study and treat
      the brain by directed gene expression. Genes with brain expression patterns of
      interest are subjected to bioinformatic analysis to delineate candidate
      regulatory regions, which are then incorporated into a panel of compact human
      MiniPromoters to drive expression to brain regions and cell types of interest.
      Using single-copy, homologous-recombination "knockins" in embryonic stem cells,
      each MiniPromoter reporter is integrated immediately 5' of the Hprt locus in the
      mouse genome. MiniPromoter expression profiles are characterized in
      differentiation assays of the transgenic cells or in mouse brains following
      transgenic mouse production. Histological examination of adult brains, eyes, and
      spinal cords for reporter gene activity is coupled to costaining with cell-type
      specific markers to define expression. The publicly available Pleiades
      MiniPromoter Project is a key resource to facilitate research on brain
      development and therapies.

PMID- 20807750
TI  - Tropical forests were the primary sources of new agricultural land in the 1980s
      and 1990s.
AB  - Global demand for agricultural products such as food, feed, and fuel is now a
      major driver of cropland and pasture expansion across much of the developing
      world. Whether these new agricultural lands replace forests, degraded forests, or
      grasslands greatly influences the environmental consequences of expansion.
      Although the general pattern is known, there still is no definitive
      quantification of these land-cover changes. Here we analyze the rich, pan
      tropical database of classified Landsat scenes created by the Food and
      Agricultural Organization of the United Nations to examine pathways of
      agricultural expansion across the major tropical forest regions in the 1980s and
      1990s and use this information to highlight the future land conversions that
      probably will be needed to meet mounting demand for agricultural products. Across
      the tropics, we find that between 1980 and 2000 more than 55% of new agricultural
      land came at the expense of intact forests, and another 28% came from disturbed
      forests. This study underscores the potential consequences of unabated
      agricultural expansion for forest conservation and carbon emissions.

PMID- 20807751
TI  - A scientific model for free will is impossible.

PMID- 20807752
TI  - H2S and O2 sensing.

PMID- 20807754
TI  - Climate denier, skeptic, or contrarian?

PMID- 20807755
TI  - Hypoxia inducible factor 1alpha and hypoxia inducible factor 2alpha play distinct
      and functionally overlapping roles in oral squamous cell carcinoma.
AB  - PURPOSE: This study aimed to investigate the functional difference between
      hypoxia inducible factor (HIF)-1alpha and HIF-2alpha in oral squamous cell
      carcinomas (OSCC). EXPERIMENTAL DESIGN: We evaluated the correlations between HIF
      1alpha and HIF-2alpha expression and the clinical-pathologic characteristics of
      97 patients with OSCC by immunohistochemical staining. OSCC cell lines
      transfected with lentivirus encoding short hairpin RNA against HIF-1alpha/2alpha
      were used to investigate the HIF-1alpha/2alpha-dependent target genes. Xenograft
      tumors in nude mice were established using cells affected by lentivirus, and
      tumor growth, angiogenesis, proliferation, and apoptosis were measured. RESULTS:
      HIF-1alpha expression was significantly associated with T stage (P = 0.004),
      lymph node involvement (P = 0.006), histologic differentiation (P = 0.013), and
      microvessel density (P = 0.014), whereas that of HIF-2alpha was associated with T
      stage (P = 0.011) and microvessel density (P = 0.005). Patients with positive HIF
      1alpha nuclear staining had a significantly worse overall survival (P < 0.001)
      and disease-free survival (P < 0.001) than those with negative HIF-1alpha
      staining. When OSCC cells were cultured at 5% O(2), only HIF-2alpha contributed
      to the expression of vascular endothelial growth factor. At 1% O(2), vascular
      endothelial growth factor was regulated by both HIF-1alpha and HIF-2alpha, but
      glucose transporter 1, carbonic anhydrase 9, and urokinase-type plasminogen
      activator receptor were regulated by HIF-1alpha rather than by HIF-2alpha.
      Knocking down HIF-1alpha or HIF-2alpha individually inhibited the xenograft tumor
      angiogenesis and growth, and knocking them down simultaneously revealed a better
      inhibitory effect than knocking down either unit alone. CONCLUSIONS: HIF-1alpha
      and HIF-2alpha correlated with different clinical-pathologic parameters,
      stabilized at different oxygen levels, and regulated different genes in OSCC.
      However, both HIF-1alpha and HIF-2alpha showed promoting roles in tumor
      angiogenesis and growth, and therapeutic outcome may benefit from combined
      targeting of HIF-1alpha and HIF-2alpha.

PMID- 20807756
TI  - Detailed distribution of NK012, an SN-38-incorporating micelle, in the liver and
      its potent antitumor effects in mice bearing liver metastases.
AB  - PURPOSE: To clarify and compare the antitumor effects and specific
      biodistribution of NK012, an SN-38-incorporating polymeric micelle, in mice
      bearing multiple liver metastases of human colon cancer HT-29 cells with
      irinotecan hydrochloride (CPT-11). EXPERIMENTAL DESIGN: The maximum tolerable
      dose of NK012 (30 mg/kg) or CPT-11 (66.7 mg/kg) was i.v. administered three times
      every 4 days to mice bearing metastases to the liver colonized 7 days after the
      portal administration of HT-29 cells (n = 6). In vivo antitumor effects were
      evaluated by bioluminescence imaging and histopathologic examination. Drug
      biodistribution was analyzed by high-performance liquid chromatography and
      fluorescence microscopy (n = 3). RESULTS: NK012 eradicated the liver metastases
      and produced a significant longer survival rate than CPT-11 (P = 0.0006). High
      performance liquid chromatography showed the prolonged distribution of NK012 and
      free SN-38 released from NK012 in the tumors, liver, and spleen for weeks after
      NK012 administration. On the other hand, the accumulation levels of CPT-11 and
      free SN-38 converted from CPT-11 rapidly decreased within 1 day after CPT-11
      administration. In the liver metastases, fluorescence microscopy and
      immunohistochemistry showed that administered NK012 was distributed mainly
      adjacent to tumor vessels after 1 day. As for the normal liver, NK012 was
      distributed in Kupffer cells instead of hepatocytes for at least 7 days after
      administration. CONCLUSION: This study suggests that NK012 is strongly effective
      against liver metastases and does not damage the liver despite the long retention
      time of NK012 in Kupffer cells.

PMID- 20807757
TI  - N-terminal domain of myelin basic protein inhibits amyloid beta-protein fibril
      assembly.
AB  - Accumulation of amyloid beta-protein (Abeta) into brain parenchymal plaques and
      the cerebral vasculature is a pathological feature of Alzheimer disease and
      related disorders. Abeta peptides readily form beta-sheet-containing oligomers
      and fibrils. Previously, we reported a strong interaction between myelin basic
      protein (MBP) and Abeta peptides that resulted in potent inhibition of fibril
      assembly (Hoos, M. D., Ahmed, M., Smith, S. O., and Van Nostrand, W. E. (2007) J.
      Biol. Chem. 282, 9952-9961; Hoos, M. D., Ahmed, M., Smith, S. O., and Van
      Nostrand, W. E. (2009) Biochemistry 48, 4720-4727). MBP is recognized as a highly
      post-translationally modified protein. In the present study, we demonstrate that
      human MBP purified from either brain or a bacterial recombinant expression system
      comparably bound to Abeta and inhibited Abeta fibril assembly indicating that
      post-translational modifications are not required for this activity. We also show
      that purified mouse brain MBP and recombinantly expressed mouse MBP similarly
      inhibited Abeta fibril formation. Through a combination of biochemical and
      ultrastructural techniques, we demonstrate that the binding site for Abeta is
      located in the N-terminal 64 amino acids of MBP and that a stable peptide (MBP1)
      comprising these residues was sufficient to inhibit Abeta fibrillogenesis. Under
      conditions comparable with those used for Abeta, the fibrillar assembly of
      amylin, another amyloidogenic peptide, was not inhibited by MBP1, although MBP1
      still bound to it. This observation suggests that the potent inhibitory effect of
      MBP on fibril formation is not general to amyloidogenic peptides. Finally, MBP1
      could prevent the cytotoxic effects of Abeta in primary cortical neurons. Our
      findings suggest that inhibition of Abeta fibril assembly by MBP, mediated
      through its N-terminal domain, could play a role in influencing amyloid formation
      in Alzheimer disease brain and corresponding mouse models.

PMID- 20807759
TI  - Calcium inhibits paracellular sodium conductance through claudin-2 by competitive
      binding.
AB  - Claudins form paracellular pores at the tight junction in epithelial cells.
      Profound depletion of extracellular calcium is well known to cause loosening of
      the tight junction with loss of transepithelial resistance. However, moderate
      variations in calcium concentrations within the physiological range can also
      regulate transepithelial permeability. To investigate the underlying molecular
      mechanisms, we studied the effects of calcium on the permeability of claudin-2,
      expressed in an inducible MDCK I cell line. We found that in the physiological
      range, calcium acts as a reversible inhibitor of the total conductance and Na(+)
      permeability of claudin-2, without causing changes in tight junction structure.
      The effect of calcium is enhanced at low Na(+) concentrations, consistent with a
      competitive effect. Furthermore, mutation of an intrapore negatively charged
      binding site, Asp-65, to asparagine partially abrogated the inhibitory effect of
      calcium. This suggests that calcium competes with Na(+) for binding to Asp-65.
      Other polyvalent cations had similar effects, including La(3+), which caused
      severe and irreversible inhibition of conductance. Brownian dynamics simulations
      demonstrated that such inhibition can be explained if Asp-65 has a relatively
      high charge density, thus favoring binding of Ca(2+) over that of Na(+), reducing
      Ca(2+) permeation by inhibiting its dissociation from this site, and decreasing
      Na(+) conductance through repulsive electrostatic interaction with Ca(2+). These
      findings may explain why hypercalcemia inhibits Na(+) reabsorption in the
      proximal tubule of the kidney.

PMID- 20807758
TI  - Insulin-like 6 is induced by muscle injury and functions as a regenerative
      factor.
AB  - The insulin-like family of factors are involved in the regulation of a variety of
      physiological processes, but the function of the family member termed insulin
      like 6 (Insl6) in skeletal muscle has not been reported. We show that Insl6 is a
      myokine that is up-regulated in skeletal muscle downstream of Akt signaling and
      in regenerating muscle in response to cardiotoxin (CTX)-induced injury. In the
      CTX injury model, myofiber regeneration was improved by the intramuscular or
      systemic delivery of an adenovirus expressing Insl6. Skeletal muscle-specific
      Insl6 transgenic mice exhibited normal muscle mass under basal conditions but
      elevated satellite cell activation and enhanced muscle regeneration in response
      to CTX injury. The Insl6-mediated regenerative response was associated with
      reductions in muscle cell apoptosis and reduced serum levels of creatine kinase
      M. Overexpression of Insl6 stimulated proliferation and reduced apoptosis in
      cultured myogenic cells. Conversely, knockdown of Insl6 reduced proliferation and
      increased apoptosis. These data indicate that Insl6 is an injury-regulated
      myokine that functions as a myogenic regenerative factor.

PMID- 20807760
TI  - Dissecting the biological role of mucin-type O-glycosylation using RNA
      interference in Drosophila cell culture.
AB  - Mucin type O-glycosylation is a highly conserved form of post-translational
      modification initiated by the family of enzymes known as the polypeptide alpha-N
      acetylgalactosaminyltransferases (ppGalNAcTs in mammals and PGANTs in
      Drosophila). To address the cellular functions of the many PGANT family members,
      RNA interference (RNAi) to each pgant gene was performed in two independent
      Drosophila cell culture lines. We demonstrate that RNAi to individual pgant genes
      results in specific reduction in gene expression without affecting the expression
      of other family members. Cells with reduced expression of individual pgant genes
      were then examined for changes in viability, morphology, adhesion, and secretion
      to assess the contribution of each family member to these cellular functions.
      Here we find that RNAi to pgant3, pgant6, or pgant7 resulted in reduced
      secretion, further supporting a role for O-glycosylation in proper secretion.
      Additionally, RNAi to pgant3 or pgant6 resulted in altered Golgi organization,
      suggesting a role for each in establishing or maintaining proper secretory
      apparatus structure. Other subcellular effects observed included multinucleated
      cells seen after RNAi to either pgant2 or pgant35A, suggesting a role for these
      genes in the completion of cytokinesis. These studies demonstrate the efficient
      and specific knockdown of pgant gene expression in two Drosophila cell culture
      systems, resulting in specific morphological and functional effects. Our work
      provides new information regarding the biological roles of O-glycosylation and
      illustrates a new platform for interrogating the cellular and subcellular effects
      of this form of post-translational modification.

PMID- 20807761
TI  - MicroRNAs regulate pituitary development, and microRNA 26b specifically targets
      lymphoid enhancer factor 1 (Lef-1), which modulates pituitary transcription
      factor 1 (Pit-1) expression.
AB  - To understand the role of microRNAs (miRNAs) in pituitary development, a group of
      pituitary-specific miRNAs were identified, and Dicer1 was then conditionally
      knocked out using the Pitx2-Cre mouse, resulting in the loss of mature miRNAs in
      the anterior pituitary. The Pitx2-Cre/Dicer1 mutant mice demonstrate growth
      retardation, and the pituitaries are hypoplastic with an abnormal branching of
      the anterior lobe, revealing a role for microRNAs in pituitary development.
      Growth hormone, prolactin, and thyroid-stimulating hormone beta-subunit
      expression were decreased in the Dicer1 mutant mouse, whereas proopiomelanocortin
      and luteinizing hormone beta-subunit expression were normal in the mutant
      pituitary. Further analyses revealed decreased Pit-1 and increased Lef-1
      expression in the mutant mouse pituitary, consistent with the repression of the
      Pit-1 promoter by Lef-1. Lef-1 directly targets and represses the Pit-1 promoter.
      miRNA-26b (miR-26b) was identified as targeting Lef-1 expression, and miR-26b
      represses Lef-1 in pituitary and non-pituitary cell lines. Furthermore, miR-26b
      up-regulates Pit-1 and growth hormone expression by attenuating Lef-1 expression
      in GH3 cells. This study demonstrates that microRNAs are critical for anterior
      pituitary development and that miR-26b regulates Pit-1 expression by inhibiting
      Lef-1 expression and may promote Pit-1 lineage differentiation during pituitary
      development.

PMID- 20807762
TI  - Regulated secretion of acid sphingomyelinase: implications for selectivity of
      ceramide formation.
AB  - The acid sphingomyelinase (aSMase) gene gives rise to two distinct enzymes,
      lysosomal sphingomyelinase (L-SMase) and secretory sphingomyelinase (S-SMase),
      via differential trafficking of a common protein precursor. However, the
      regulation of S-SMase and its role in cytokine-induced ceramide formation remain
      ill defined. To determine the role of S-SMase in cellular sphingolipid
      metabolism, MCF7 breast carcinoma cells stably transfected with V5-aSMase(WT)
      were treated with inflammatory cytokines. Interleukin-1beta and tumor necrosis
      factor-alpha induced a time- and dose-dependent increase in S-SMase secretion and
      activity, coincident with selective elevations in cellular C(16)-ceramide. To
      establish a role for S-SMase, we utilized a mutant of aSMase (S508A) that is
      shown to retain L-SMase activity, but is defective in secretion. MCF7 expressing
      V5-aSMase(WT) exhibited increased S-SMase and L-SMase activity, as well as
      elevated cellular levels of specific long-chain and very long-chain ceramide
      species relative to vector control MCF7. Interestingly, elevated levels of only
      certain very long-chain ceramides were evident in V5-aSMase(S508A) MCF7.
      Secretion of the S508A mutant was also defective in response to IL-1beta, as was
      the regulated generation of C(16)-ceramide. Taken together, these data support a
      crucial role for Ser(508) in the regulation of S-SMase secretion, and they
      suggest distinct metabolic roles for S-SMase and L-SMase.

PMID- 20807763
TI  - The carboxyl-terminal end of Cox1 is required for feedback assembly regulation of
      Cox1 synthesis in Saccharomyces cerevisiae mitochondria.
AB  - Synthesis of the largest cytochrome c oxidase (CcO) subunit, Cox1, on yeast
      mitochondrial ribosomes is coupled to assembly of CcO. The translational
      activator Mss51 is sequestered in early assembly intermediate complexes by an
      interaction with Cox14 that depends on the presence of newly synthesized Cox1. If
      CcO assembly is prevented, the level of Mss51 available for translational
      activation is reduced. We deleted the C-terminal 11 or 15 residues of Cox1 by
      site-directed mutagenesis of mtDNA. Although these deletions did not prevent
      respiratory growth of yeast, they eliminated the assembly-feedback control of
      Cox1 synthesis. Furthermore, these deletions reduced the strength of the Mss51
      Cox14 interaction as detected by co-immunoprecipitation, confirming the
      importance of the Cox1 C-terminal residues for Mss51 sequestration. We surveyed a
      panel of mutations that block CcO assembly for the strength of their effect on
      Cox1 synthesis, both by pulse labeling and expression of the ARG8(m) reporter
      fused to COX1. Deletion of the nuclear gene encoding Cox6, one of the first
      subunits to be added to assembling CcO, caused the most severe reduction in Cox1
      synthesis. Deletion of the C-terminal 15 amino acids of Cox1 increased Cox1
      synthesis in the presence of each of these mutations, except pet54. Our data
      suggest a novel activity of Pet54 required for normal synthesis of Cox1 that is
      independent of the Cox1 C-terminal end.

PMID- 20807764
TI  - A cell-permeable Stat3 SH2 domain mimetic inhibits Stat3 activation and induces
      antitumor cell effects in vitro.
AB  - Given the role of constitutively active Signal Transducer and Activator of
      Transcription (Stat) 3 in human tumors, Stat3 inhibitors would be useful as novel
      therapeutics and as tools for probing Stat3-mediated tumor processes. We herein
      report that a 28-mer peptide, SPI, derived from the Stat3 SH2 domain, replicates
      Stat3 biochemical properties. Studies show SPI and Stat3 (or Stat3 SH2 domain)
      bind with similar affinities to known Stat3-binding phosphotyrosine (pY) peptide
      motifs, including those of the epidermal growth factor receptor (EGFR) and the
      high-affinity, IL-6R/gp130-derived pY-peptide, GpYLPQTV-NH(2). Consequently, SPI
      functions as a potent and selective inhibitor of Stat3 SH2 domain:pTyr
      interactions and disrupts the binding of Stat3 to the IL-6R/gp130 peptide,
      GpYLPQTV-NH(2). Fluorescence imaging and immunofluorescence staining/laser
      scanning confocal microscopy show SPI is cell membrane-permeable, associates with
      the cytoplasmic tail of EGFR in NIH3T3/hEGFR, and is present in the cytoplasm,
      but strongly localized at the plasma membrane and in the nucleus in malignant
      cells harboring persistently active Stat3. Moreover, SPI specifically blocks
      constitutive Stat3 phosphorylation, DNA binding activity, and transcriptional
      function in malignant cells, with little or no effect on the induction of Stat1,
      Stat5, and Erk1/2(MAPK) pathways, or on general pTyr profile at the
      concentrations that inhibit Stat3 activity. Significantly, treatment with SPI of
      human breast, pancreatic, prostate, and non-small cell lung cancer cells
      harboring constitutively active Stat3 induced extensive morphology changes,
      associated with viability loss and apoptosis. Our study identifies SPI as a novel
      molecular probe for interrogating Stat3 signaling and that functions as a
      selective inhibitor of Stat3 activation with antitumor cell effects.

PMID- 20807765
TI  - Molecular mechanisms of EAST/SeSAME syndrome mutations in Kir4.1 (KCNJ10).
AB  - Inwardly rectifying potassium channel Kir4.1 is critical for glial function,
      control of neuronal excitability, and systemic K(+) homeostasis. Novel mutations
      in Kir4.1 have been associated with EAST/SeSAME syndrome, characterized by mental
      retardation, ataxia, seizures, hearing loss, and renal salt waste. Patients are
      homozygous for R65P, G77R, C140R or T164I; or compound heterozygous for
      A167V/R297C or R65P/R199Stop, a deletion of the C-terminal half of the protein.
      We investigated the functional significance of these mutations by radiotracer
      efflux and inside-out membrane patch clamping in COSm6 cells expressing homomeric
      Kir4.1 or heteromeric Kir4.1/Kir5.1 channels. All of the mutations compromised
      channel function, but the underlying mechanisms were different. R65P, T164I, and
      R297C caused an alkaline shift in pH sensitivity, indicating that these positions
      are crucial for pH sensing and pore gating. In R297C, this was due to disruption
      of intersubunit salt bridge Glu(288)-Arg(297). C140R breaks the Cys(108)-Cys(140)
      disulfide bond essential for protein folding and function. A167V did not affect
      channel properties but may contribute to decreased surface expression in
      A167V/R297C. In G77R, introduction of a positive charge within the bilayer may
      affect channel structure or gating. R199Stop led to a dramatic decrease in
      surface expression, but channel activity was restored by co-expression with
      intact subunits, suggesting remarkable tolerance for truncation of the
      cytoplasmic domain. These results provide an explanation for the molecular
      defects that underlie the EAST/SeSAME syndrome.

PMID- 20807766
TI  - PP2A:B56{epsilon}, a substrate of caspase-3, regulates p53-dependent and p53
      independent apoptosis during development.
AB  - Protein phosphatase 2A (PP2A) is one of the most abundantly expressed
      serine/threonine protein phosphatases. A large body of evidence suggests that
      PP2A is a tumor suppressor and plays critical roles in regulating apoptosis. PP2A
      is a heterotrimeric protein complex. Its substrate specificity, localization, and
      activity are regulated by regulatory subunits of PP2A. A recent study has
      demonstrated that single nucleotide polymorphism in B56epsilon (PPP2R5E), a B56
      family regulatory subunit of PP2A, is associated with human soft tissue sarcoma.
      This raises the possibility that B56epsilon is involved in tumorigenesis and
      plays important roles in regulating apoptosis. However, this hypothesis has not
      been tested experimentally. Our previous studies revealed that B56epsilon
      regulates a number of developmental signaling pathways during early embryonic
      patterning. Here we report novel functions of B56epsilon in regulating apoptosis.
      We provide evidence that B56epsilon has both anti- and pro-apoptotic functions.
      B56epsilon suppresses p53-independent apoptosis during neural development, but
      triggers p53-dependent apoptosis. Mechanistically, B56epsilon regulates the p53
      dependent apoptotic pathway solely through controlling the stability of p53
      protein. In addition to its function in regulating apoptosis, we show that
      B56epsilon undergoes proteolytic cleavage. The cleavage of B56epsilon is mediated
      by caspase-3 and occurs on the carboxyl side of an evolutionarily conserved N
      terminal "DKXD" motif. These results demonstrate that B56epsilon, a substrate of
      caspase-3, is an essential regulator of apoptosis. So far, we have identified an
      alternative translation isoform and a caspase cleavage product of B56epsilon. The
      significance of post-transcriptional regulation of B56epsilon is discussed.

PMID- 20807767
TI  - Joint functions of protein residues and NADP(H) in oxygen activation by flavin
      containing monooxygenase.
AB  - The reactivity of flavoenzymes with dioxygen is at the heart of a number of
      biochemical reactions with far reaching implications for cell physiology and
      pathology. Flavin-containing monooxygenases are an attractive model system to
      study flavin-mediated oxygenation. In these enzymes, the NADP(H) cofactor is
      essential for stabilizing the flavin intermediate, which activates dioxygen and
      makes it ready to react with the substrate undergoing oxygenation. Our studies
      combine site-directed mutagenesis with the usage of NADP(+) analogues to dissect
      the specific roles of the cofactors and surrounding protein matrix. The highlight
      of this "double-engineering" approach is that subtle alterations in the hydrogen
      bonding and stereochemical environment can drastically alter the efficiency and
      outcome of the reaction with oxygen. This is illustrated by the seemingly
      marginal replacement of an Asn to Ser in the oxygen-reacting site, which
      inactivates the enzyme by effectively converting it into an oxidase. These data
      rationalize the effect of mutations that cause enzyme deficiency in patients
      affected by the fish odor syndrome. A crucial role of NADP(+) in the oxygenation
      reaction is to shield the reacting flavin N5 atom by H-bond interactions. A Tyr
      residue functions as backdoor that stabilizes this crucial binding conformation
      of the nicotinamide cofactor. A general concept emerging from this analysis is
      that the two alternative pathways of flavoprotein-oxygen reactivity (oxidation
      versus monooxygenation) are predicted to have very similar activation barriers.
      The necessity of fine tuning the hydrogen-bonding, electrostatics, and
      accessibility of the flavin will represent a challenge for the design and
      development of oxidases and monoxygenases for biotechnological applications.

PMID- 20807768
TI  - Mutational tuning of galectin-3 specificity and biological function.
AB  - Galectins are defined by a conserved beta-galactoside binding site that has been
      linked to many of their important functions in e.g. cell adhesion, signaling, and
      intracellular trafficking. Weak adjacent sites may enhance or decrease affinity
      for natural beta-galactoside-containing glycoconjugates, but little is known
      about the biological role of this modulation of affinity (fine specificity). We
      have now produced 10 mutants of human galectin-3, with changes in these adjacent
      sites that have altered carbohydrate-binding fine specificity but that retain the
      basic beta-galactoside binding activity as shown by glycan-array binding and a
      solution-based fluorescence anisotropy assay. Each mutant was also tested in two
      biological assays to provide a correlation between fine specificity and function.
      Galectin-3 R186S, which has selectively lost affinity for LacNAc, a disaccharide
      moiety commonly found on glycoprotein glycans, has lost the ability to activate
      neutrophil leukocytes and intracellular targeting into vesicles. K176L has
      increased affinity for beta-galactosides substituted with GlcNAcbeta1-3, as found
      in poly-N-acetyllactosaminoglycans, and increased potency to activate neutrophil
      leukocytes even though it has lost other aspects of galectin-3 fine specificity.
      G182A has altered carbohydrate-binding fine specificity and altered intracellular
      targeting into vesicles, a possible link to the intracellular galectin-3-mediated
      anti-apoptotic effect known to be lost by this mutant. Finally, the mutants have
      helped to define the differences in fine specificity shown by Xenopus, mouse, and
      human galectin-3 and, as such, the evidence for adaptive change during evolution.

PMID- 20807769
TI  - Mechanism of phosphorylation-induced activation of phospholipase C-gamma
      isozymes.
AB  - The lipase activity of most phospholipases C (PLCs) is basally repressed by a
      highly degenerate and mostly disordered X/Y linker inserted within the catalytic
      domain. Release of this auto-inhibition is driven by electrostatic repulsion
      between the plasma membrane and the electronegative X/Y linker. In contrast, PLC
      gamma isozymes (PLC-gamma1 and -gamma2) are structurally distinct from other PLCs
      because multiple domains are present in their X/Y linker. Moreover, although many
      tyrosine kinases directly phosphorylate PLC-gamma isozymes to enhance their
      lipase activity, the underlying molecular mechanism of this activation remains
      unclear. Here we define the mechanism for the unique regulation of PLC-gamma
      isozymes by their X/Y linker. Specifically, we identify the C-terminal SH2 domain
      within the X/Y linker as the critical determinant for auto-inhibition. Tyrosine
      phosphorylation of the X/Y linker mediates high affinity intramolecular
      interaction with the C-terminal SH2 domain that is coupled to a large
      conformational rearrangement and release of auto-inhibition. Consequently, PLC
      gamma isozymes link phosphorylation to phospholipase activation by elaborating
      upon primordial regulatory mechanisms found in other PLCs.

PMID- 20807770
TI  - Oligomeric amyloid-{beta} inhibits the proteolytic conversion of brain-derived
      neurotrophic factor (BDNF), AMPA receptor trafficking, and classical
      conditioning.
AB  - Amyloid-beta (Abeta) peptide is thought to have a significant role in the
      progressive memory loss observed in patients with Alzheimer disease and inhibits
      synaptic plasticity in animal models of learning. We previously demonstrated that
      brain-derived neurotrophic factor (BDNF) is critical for synaptic AMPA receptor
      delivery in an in vitro model of eyeblink classical conditioning. Here, we report
      that acquisition of conditioned responses was significantly attenuated by bath
      application of oligomeric (200 nm), but not fibrillar, Abeta peptide. Western
      blotting revealed that BDNF protein expression during conditioning is
      significantly reduced by treatment with oligomeric Abeta, as were phosphorylation
      levels of cAMP-response element-binding protein (CREB), Ca(2+)/calmodulin
      dependent protein kinase II (CaMKII), Ca(2+)/calmodulin-dependent protein kinase
      IV (CaMKIV), and ERK. However, levels of PKA and PKCzeta/lambda were unaffected,
      as was PDK-1. Protein localization studies using confocal imaging indicate that
      oligomeric Abeta, but not fibrillar or scrambled forms, suppresses colocalization
      of GluR1 and GluR4 AMPA receptor subunits with synaptophysin, indicating that
      trafficking of these subunits to synapses during the conditioning procedure is
      blocked. In contrast, coapplication of BDNF with oligomeric Abeta significantly
      reversed these findings. Interestingly, a tolloid-like metalloproteinase in
      turtle, tTLLs (turtle tolloid-like protein), which normally processes the
      precursor proBDNF into mature BDNF, was found to degrade oligomeric Abeta into
      small fragments. These data suggest that an Abeta-induced reduction in BDNF,
      perhaps due to interference in the proteolytic conversion of proBDNF to BDNF,
      results in inhibition of synaptic AMPA receptor delivery and suppression of the
      acquisition of conditioning.

PMID- 20807771
TI  - Identification of an endothelin-converting enzyme-2-specific fluorigenic
      substrate and development of an in vitro and ex vivo enzymatic assay.
AB  - Endothelin-converting enzyme-2 (ECE-2) is a membrane-bound zinc-dependent
      metalloprotease that shares a high degree of sequence homology with ECE-1, but
      displays an acidic pH optimum characteristic of maturing enzymes acting late in
      the secretory pathway. Although ECE-2, like ECE-1, can cleave the big endothelin
      intermediate to produce the vasoconstrictive endothelin peptide, its true
      physiological function remains to be elucidated, a task that is hampered by the
      lack of specific tools to study and discriminate ECE-2 from ECE-1, i.e. specific
      substrates and/or specific inhibitors. To fill this gap, we searched for novel
      ECE-specific peptide substrates. To this end, peptides derived from the big
      endothelin intermediate were tested using ECE-1 and ECE-2, leading to the
      identification of an ECE-1-specific substrate. Moreover, screening of our
      proprietary fluorigenic peptide Fluofast(r) libraries using ECE-1 and ECE-2
      allowed the identification of Ac-SKG-Pya-F-W-Nop-GGK-NH(2) (PL405), as a specific
      and high affinity ECE-2 substrate. Indeed, ECE-2 cleaved PL405 at the Pya-F amide
      bond with a specificity constant (k(cat)/K(m)) of 8.1 +/- 0.9 * 10(3) M(-1) s(
      1). Using this novel substrate, we also characterized the first potent (K(i) =
      7.7 +/- 0.3 nM) and relatively selective ECE-2 inhibitor and developed a
      quantitative fluorigenic ECE-2 assay. The assay was used to study the ex vivo ECE
      2 activity in wild type and ECE-2 knock-out tissues and was found to truly
      reflect ECE-2 expression patterns. The PL405 assay is thus the first tool to
      study ECE-2 inhibition using high throughput screening or for ex vivo ECE-2
      quantification.

PMID- 20807772
TI  - Dopamine D1-D2 receptor Heteromer-mediated calcium release is desensitized by D1
      receptor occupancy with or without signal activation: dual functional regulation
      by G protein-coupled receptor kinase 2.
AB  - We identified that activation of the G(q)-linked dopamine D1-D2 receptor hetero
      oligomer generates a PLC-dependent intracellular calcium signal. Confocal FRET
      between endogenous dopamine D1 and D2 receptors in striatal neurons confirmed a
      physical interaction between them. Pretreatment with SKF 83959, which selectively
      activates the D1-D2 receptor heteromer, or SKF 83822, which only activates the D1
      receptor homo-oligomer, led to rapid desensitization of the D1-D2 receptor
      heteromer-mediated calcium signal in both heterologous cells and striatal
      neurons. This desensitization response was mediated through selective occupancy
      of the D1 receptor binding pocket. Although SKF 83822 was unable to activate the
      D1-D2 receptor heteromer, it still permitted desensitization of the calcium
      signal. This suggested that occupancy of the D1 receptor binding pocket by SKF
      83822 resulted in conformational changes sufficient for desensitization without
      heteromer activation. Bioluminescence resonance energy transfer and co
      immunoprecipitation studies indicated an agonist-induced physical association
      between the D1-D2 receptor heteromeric complex and GRK2. Increased expression of
      GRK2 led to a decrease in the calcium signal with or without prior exposure to
      either SKF 83959 or SKF 83822. GRK2 knockdown by siRNA led to an increase in the
      signal after pretreatment with either agonist. Expression of the catalytically
      inactive and RGS (regulator of G protein signaling)-mutated GRK2 constructs each
      led to a partial recovery of the GRK2-attenuated calcium signal. These results
      indicated that desensitization of the dopamine D1-D2 receptor heteromer-mediated
      signal can occur by agonist occupancy even without activation and is dually
      regulated by both the catalytic and RGS domains of GRK2.

PMID- 20807773
TI  - Carbon flow of heliobacteria is related more to clostridia than to the green
      sulfur bacteria.
AB  - The recently discovered heliobacteria are the only Gram-positive photosynthetic
      bacteria that have been cultured. One of the unique features of heliobacteria is
      that they have properties of both the photosynthetic green sulfur bacteria
      (containing the type I reaction center) and Clostridia (forming heat-resistant
      endospores). Most of the previous studies of heliobacteria, which are strict
      anaerobes and have the simplest known photosynthetic apparatus, have focused on
      energy and electron transfer processes. It has been assumed that like green
      sulfur bacteria, the major carbon flow in heliobacteria is through the
      (incomplete) reductive (reverse) tricarboxylic acid cycle, whereas the lack of
      CO(2)-enhanced growth has not been understood. Here, we report studies to fill
      the knowledge gap of heliobacterial carbon metabolism. We confirm that the CO(2)
      anaplerotic pathway is active during phototrophic growth and that isoleucine is
      mainly synthesized from the citramalate pathway. Furthermore, to our surprise,
      our results suggest that the oxidative (forward) TCA cycle is operative and more
      active than the previously reported reductive (reverse) tricarboxylic acid cycle.
      Both isotopomer analysis and activity assays suggest that citrate is produced by
      a putative (Re)-citrate synthase and then enters the oxidative (forward) TCA
      cycle. Moreover, in contrast to (Si)-citrate synthase, (Re)-citrate synthase
      produces a different isomer of 2-fluorocitrate that is not expected to inhibit
      the activity of aconitase.

PMID- 20807774
TI  - Gene expression profiles linked to AT1 angiotensin receptors in the kidney.
AB  - To characterize gene expression networks linked to AT(1) angiotensin receptors in
      the kidney, we carried out genome-wide transcriptional analysis of RNA from
      kidneys of wild-type (WT) and AT(1A) receptor-deficient mice (KOs) at baseline
      and after 2 days of angiotensin II infusion (1,000 ng.kg(-1).min(-1)). At
      baseline, 405 genes were differentially expressed (>1.5*) between WT and KO
      kidneys. Of these, >80% were upregulated in the KO group including genes involved
      in inflammation, oxidative stress, and cell proliferation. After 2 days of
      angiotensin II infusion in WT mice, expression of ~805 genes was altered (18%
      upregulated, 82% repressed). Genes in metabolism and ion transport pathways were
      upregulated while there was attenuated expression of genes protective against
      oxidative stress including glutathione synthetase and mitochondrial superoxide
      dismutase 2. Angiotensin II infusion had little effect on blood pressure in KOs.
      Nonetheless, expression of >250 genes was altered in kidneys from KO mice during
      angiotensin II infusion; 14% were upregulated, while 86% were repressed including
      genes involved in immune responses, angiogenesis, and glutathione metabolism.
      Between WT and KO kidneys during angiotensin II infusion, 728 genes were
      differentially expressed; 10% were increased and 90% were decreased in the WT
      group. Differentially regulated pathways included those involved in ion
      transport, immune responses, metabolism, apoptosis, cell proliferation, and
      oxidative stress. This genome-wide assessment should facilitate identification of
      critical distal pathways linked to blood pressure regulation.

PMID- 20807776
TI  - A point mutation in the dynein heavy chain gene leads to striatal atrophy and
      compromises neurite outgrowth of striatal neurons.
AB  - The molecular motor dynein and its associated regulatory subunit dynactin have
      been implicated in several neurodegenerative conditions of the basal ganglia,
      such as Huntington's disease (HD) and Perry syndrome, an atypical Parkinson-like
      disease. This pathogenic role has been largely postulated from the existence of
      mutations in the dynactin subunit p150(Glued). However, dynactin is also able to
      act independently of dynein, and there is currently no direct evidence linking
      dynein to basal ganglia degeneration. To provide such evidence, we used here a
      mouse strain carrying a point mutation in the dynein heavy chain gene that
      impairs retrograde axonal transport. These mice exhibited motor and behavioural
      abnormalities including hindlimb clasping, early muscle weakness, incoordination
      and hyperactivity. In vivo brain imaging using magnetic resonance imaging showed
      striatal atrophy and lateral ventricle enlargement. In the striatum, altered
      dopamine signalling, decreased dopamine D1 and D2 receptor binding in positron
      emission tomography SCAN and prominent astrocytosis were observed, although there
      was no neuronal loss either in the striatum or substantia nigra. In vitro, dynein
      mutant striatal neurons displayed strongly impaired neuritic morphology.
      Altogether, these findings provide a direct genetic evidence for the requirement
      of dynein for the morphology and function of striatal neurons. Our study supports
      a role for dynein dysfunction in the pathogenesis of neurodegenerative disorders
      of the basal ganglia, such as Perry syndrome and HD.

PMID- 20807775
TI  - Phenotypic variability and genetic susceptibility to genomic disorders.
AB  - The duplication architecture of the human genome predisposes our species to
      recurrent copy number variation and disease. Emerging data suggest that this
      mechanism of mutation contributes to both common and rare diseases. Two features
      regarding this form of mutation have emerged. First, common structural
      polymorphisms create susceptible and protective chromosomal architectures. These
      structural polymorphisms occur at varying frequencies in populations, leading to
      different susceptibility and ethnic predilection. Second, a subset of
      rearrangements shows extreme variability in expressivity. We propose that two
      types of genomic disorders may be distinguished: syndromic forms where the
      phenotypic features are largely invariant and those where the same molecular
      lesion associates with a diverse set of diagnoses including epilepsy,
      schizophrenia, autism, intellectual disability and congenital malformations. Copy
      number variation analyses of patient genomes reveal that disease type and
      severity may be explained by the occurrence of additional rare events and their
      inheritance within families. We propose that the overall burden of copy number
      variants creates differing sensitized backgrounds during development leading to
      different thresholds and disease outcomes. We suggest that the accumulation of
      multiple high-penetrant alleles of low frequency may serve as a more general
      model for complex genetic diseases, posing a significant challenge for
      diagnostics and disease management.

PMID- 20807779
TI  - BNP7787-mediated modulation of paclitaxel- and cisplatin-induced aberrant
      microtubule protein polymerization in vitro.
AB  - Taxane and platinum drugs are important agents in the treatment of cancer and
      have shown activity against a variety of tumors, including ovarian, breast, and
      lung cancer, either as single agents or in combination with other chemotherapy
      drugs. However, a serious and prevalent side effect of taxane (docetaxel and all
      formulations/derivatives of paclitaxel) and platinum (cisplatin, carboplatin, and
      oxaliplatin) agents is dose-limiting chemotherapy-induced peripheral neuropathy
      (CIPN). CIPN can result in treatment delays, dose modifications, and, in severe
      cases, discontinuation of chemotherapy. Consequently, effective treatments for
      CIPN are needed. Dimesna (BNP7787; Tavocept; disodium 2,2'-dithio-bis
      ethanesulfonate) is an investigational drug that is undergoing international
      clinical development as a treatment that is coadministered with first-line taxane
      and platinum combination chemotherapy in patients with inoperable advanced
      primary adenocarcinoma of the lung. BNP7787 is currently being developed with the
      objective of increasing the survival of cancer patients receiving taxane- and/or
      cisplatin-based chemotherapy. Additional data indicate that BNP7787 may also
      protect against common and serious chemotherapy-induced toxicities, including
      chemotherapy-induced anemia, nausea, emesis, nephrotoxicity, and neuropathy,
      without interfering with antitumor activity of the chemotherapeutic agent(s).
      Studies herein show that BNP7787 prevents aberrant microtubule protein (MTP)
      polymerization that is caused by exposure of MTP to paclitaxel or cisplatin.
      BNP7787 modulates paclitaxel-induced hyperpolymerization of MTP in a dose
      dependent manner, and mesna, an in vivo metabolite of BNP7787, protects against
      time-dependent cisplatin-induced inactivation of MTP. We propose that
      interactions between BNP7787 and MTP may play a role in BNP7787-mediated
      protection against CIPN.

PMID- 20807777
TI  - Inhaled anesthetic responses of recombinant receptors and knockin mice harboring
      alpha2(S270H/L277A) GABA(A) receptor subunits that are resistant to isoflurane.
AB  - The mechanism by which the inhaled anesthetic isoflurane produces amnesia and
      immobility is not understood. Isoflurane modulates GABA(A) receptors (GABA(A)-Rs)
      in a manner that makes them plausible targets. We asked whether GABA(A)-R alpha2
      subunits contribute to a site of anesthetic action in vivo. Previous studies
      demonstrated that Ser270 in the second transmembrane domain is involved in the
      modulation of GABA(A)-Rs by volatile anesthetics and alcohol, either as a binding
      site or a critical allosteric residue. We engineered GABA(A)-Rs with two
      mutations in the alpha2 subunit, changing Ser270 to His and Leu277 to Ala.
      Recombinant receptors with these mutations demonstrated normal affinity for GABA,
      but substantially reduced responses to isoflurane. We then produced mutant
      (knockin) mice in which this mutated subunit replaced the wild-type alpha2
      subunit. The adult mutant mice were overtly normal, although there was evidence
      of enhanced neonatal mortality and fear conditioning. Electrophysiological
      recordings from dentate granule neurons in brain slices confirmed the decreased
      actions of isoflurane on mutant receptors contributing to inhibitory synaptic
      currents. The loss of righting reflex EC(50) for isoflurane did not differ
      between genotypes, but time to regain the righting reflex was increased in N(2)
      generation knockins. This effect was not observed at the N(4) generation.
      Isoflurane produced immobility (as measured by tail clamp) and amnesia (as
      measured by fear conditioning) in both wild-type and mutant mice, and potencies
      (EC(50)) did not differ between the strains for these actions of isoflurane.
      Thus, immobility or amnesia does not require isoflurane potentiation of the
      alpha2 subunit.

PMID- 20807778
TI  - Psychiatric characterization of children with genetic causes of hyperandrogenism.
AB  - OBJECTIVE: Very little is known about the mental health status in children with
      genetic causes of hyperandrogenism. This study sought to characterize psychiatric
      morbidity in this group. DESIGN/METHODS: Children (8-18 years) with the diagnosis
      of classic congenital adrenal hyperplasia (CAH) or familial male precocious
      puberty (FMPP) underwent a semi-structured psychiatric interview, the Kiddie
      Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version.
      According to sex and the literature, incidence of identified psychopathology was
      compared between the two endocrinological groups. We evaluated 72 patients: 54
      CAH (21 females) and 18 FMPP. RESULTS: Twenty-four (44.4%) CAH patients and 10
      (55.6%) FMPP patients met the criteria for at least one lifetime psychiatric
      diagnosis. Attention-deficit hyperactivity disorder (ADHD) was present in 18.2%
      of CAH males, 44.4% of FMPP males, and one case (4.8%) in CAH females. A high
      rate of anxiety disorders was also found in all the three groups (17-21%).
      Relative to females with CAH, the FMPP patients exhibited higher rates of ADHD.
      Age at diagnosis and the treatment modalities were not associated with
      psychopathology. Rates of psychiatric disorder, specifically ADHD and anxiety
      disorders, were higher than in the general population. CONCLUSION: Although
      anxiety disorders may occur at an increased rate in children with chronic
      illness, androgens may contribute to higher risk for psychopathology in pediatric
      patients with genetic cause of excess androgen. Early diagnosis and treatment of
      childhood hyperandrogenism is essential for optimal development. The results
      suggest that assessment for psychiatric disorders should be part of the routine
      evaluation of these patients.

PMID- 20807780
TI  - Discovery and characterization of novel mutant FLT3 kinase inhibitors.
AB  - For a subpopulation of acute myeloid leukemia (AML) patients, the constitutively
      activated tyrosine kinase, mutant FLT3, has emerged as a promising target for
      therapy. The development of drug resistance, however, is a growing concern for
      mutant FLT3 inhibitors, such as PKC412. Potential therapeutic benefit can arise
      from the combination of two structurally diverse inhibitors that target-but bind
      differently to-the same protein or from two inhibitors with completely different
      mechanisms of action. Thus, there is a need for identification and development of
      novel FLT3 inhibitors that have the ability to positively combine with PKC412 or
      standard chemotherapeutic agents used to treat AML as a way to suppress the
      development of drug resistance and consequently prolong disease remission. Here,
      we report the effects of the novel type II ATP-competitive inhibitors, HG-7-85-01
      and HG-7-86-01, which potently and selectively target mutant FLT3 protein kinase
      activity and inhibit the proliferation of cells harboring FLT3-ITD or FLT3 kinase
      domain point mutants via induction of apoptosis and cell cycle inhibition.
      Antileukemic activity of HG-7-85-01 was shown in vivo to be comparable with that
      observed with PKC412 in a bioluminescence assay using NCr nude mice harboring
      Ba/F3-FLT3-ITD-luc+ cells. HG-7-85-01 was also observed to override PKC412
      resistance. Finally, HG-7-85-01 and HG-7-86-01 synergized with PKC412 and
      standard chemotherapeutic agents against mutant PKC412-sensitive and some PKC412
      resistant, FLT3-positive cells. Thus, we present a structurally novel class of
      FLT3 inhibitors that warrants consideration for clinical testing against drug
      resistant disease in AML patients.

PMID- 20807781
TI  - Architectonics of phage-liposome nanowebs as optimized photosensitizer vehicles
      for photodynamic cancer therapy.
AB  - Filamentous M13 phage can be engineered to display cancer cell-targeting or tumor
      homing peptides through phage display. It would be highly desirable if the tumor
      targeting phage can also carry anticancer drugs to deliver them to the cancer
      cells. We studied the evolution of structures of the complexes between anionic
      filamentous M13 phage and cationic serum-stable liposomes that encapsulate the
      monomeric photosensitizer zinc naphthalocyanine. At specific phage-liposome
      ratios, multiple phage nanofibers and liposomes are interwoven into a "nanoweb."
      The chemical and biological properties of the phage-liposome nanoweb were
      evaluated for possible application in drug delivery. This study highlights the
      ability of phage-liposome nanowebs to serve as efficient carriers in the
      transport of photosensitizers to cancer cells.

PMID- 20807782
TI  - Molecular therapy targeting Sonic hedgehog and hepatocyte growth factor signaling
      in a mouse model of medulloblastoma.
AB  - The use of genetically engineered mice has provided insights into the molecular
      pathogenesis of the pediatric brain tumor medulloblastoma and revealed promising
      therapeutic targets. Ectopic expression of Sonic hedgehog (Shh) in cerebellar
      neural progenitor cells induces medulloblastomas in mice, and coexpression of
      hepatocyte growth factor (HGF) enhances Shh-induced tumor formation. To determine
      whether Shh + HGF-driven medulloblastomas were responsive to Shh signaling
      blockade and whether treatment response could be enhanced by combination therapy
      targeting both HGF and Shh signaling pathways, we carried out a survival study in
      mice. We induced medulloblastomas by retrovirus-mediated expression of Shh and
      HGF, after which we treated the mice systemically with (a) HGF-neutralizing
      monoclonal antibody L2G7, (b) Shh signaling inhibitor cyclopamine, (c) Shh
      neutralizing monoclonal antibody 5E1, (d) L2G7 + cyclopamine, or (e) L2G7 + 5E1.
      We report that monotherapy targeting either HGF signaling or Shh signaling
      prolonged survival and that anti-HGF therapy had a more durable response than Shh
      targeted therapy. The effect of L2G7 + 5E1 combination therapy on cumulative
      survival was equivalent to that of L2G7 monotherapy and that of L2G7 +
      cyclopamine therapy was worse. The principal mechanism by which Shh- and HGF
      targeted therapies inhibited tumor growth was a potent apoptotic death response
      in tumor cells, supplemented by a weaker suppressive effect on proliferation. Our
      observation that combination therapy either failed to improve or even reduced
      survival in mice bearing Shh + HGF-induced medulloblastomas compared with
      monotherapy underscores the importance of preclinical testing of molecular
      targeted therapies in animal models of tumors in which the targeted pathways are
      known to be active.

PMID- 20807783
TI  - Targeting insulin-like growth factor signaling: rational combination strategies.

PMID- 20807784
TI  - Effects of recombinant human erythropoietin in normal humans.
AB  - This review describes some of the physiological effects of recombinant human
      erythropoietin (EPO) in healthy humans. At the blood level EPO increases the
      arterial O(2) content not only by increasing red blood cell volume, but also by
      an equally important decrease in plasma volume. Well before that, EPO causes a
      prompt decrease in plasma levels of renin and aldosterone. Renal clearance
      studies suggest that EPO decreases renal proximal tubular reabsorption rate
      leading to activation of the tubuloglomerular feedback mechanism and a fall in
      glomerular filtration rate. Thus, treatment with EPO may result in suppression of
      endogenous EPO production through a decrease in intrarenal oxygen consumption.
      EPO elevates the arterial blood pressure even in healthy subjects. The receptor
      for EPO is present in many tissues. However, the functional effects of EPO in the
      skeletal muscle seem limited, and although it has been speculated that non
      erythropoietic effects of EPO (angiogenesis, shift in muscle fibre types,
      cognitive effects) may be responsible for the increase in exercise performance,
      this has not been confirmed. EPO-induced haemodynamic effects call for careful
      monitoring during the administration period. The metabolic, hormonal and renal
      effects of EPO do not seem to range beyond physiologically acceptable limits and
      are reversible. Taken together, EPO seems safe to use for experimental purposes
      in healthy volunteers.

PMID- 20807785
TI  - Regional heterogeneity of alpha-adrenoreceptor subtypes in arteriolar networks of
      mouse skeletal muscle.
AB  - Activation of vascular adrenoreceptors (ARs) governs the magnitude and
      distribution of muscle blood flow in accord with the distribution of AR subtypes.
      Functional studies in the rat cremaster muscle indicate that alpha1ARs
      predominate in proximal arterioles (first-order, 1A) while alpha2ARs predominate
      in distal arterioles (third-order, 3A). However, little is known of AR subtype
      distribution in arteriolar networks of locomotor skeletal muscles, particularly
      in the mouse. We tested the hypotheses that functional AR subtypes exhibit
      heterogeneity among branches of arteriolar networks in a locomotor muscle and
      that the nature of this heterogeneity can vary between muscles having diverse
      functions. In anaesthetized male C57BL/6J mice (3 months old), concentration
      response curves (10(-9) m to 10(-5) m, 0.5 log increments) were evaluated in the
      gluteus maximus muscle superfused with physiological saline solution (35 degrees
      C, pH 7.4; n >= 5 per group). Noradrenaline (NA, non-selective alphaAR agonist)
      constricted 1A, 2A and 3A with similar potency and efficacy. Phenylephrine (PE;
      alpha1AR agonist) evoked greater (P < 0.05) constriction in 3A (inhibited by 10(
      8) m prazosin; alpha1AR antagonist) while UK 14304 (UK; alpha2AR agonist) evoked
      greater (P < 0.05) constriction in 1A (inhibited by 10(-7) m rauwolscine;
      alpha2AR antagonist). Isoproterenol (isoprenaline; betaAR agonist) dilated 1A, 2A
      and 3A near-maximally with similar potency and efficacy; these dilatations were
      inhibited by 10(-7) m propranolol (betaAR antagonist) which otherwise had no
      effect on responses to NA, PE, or UK. Complementary experiments in the mouse
      cremaster muscle revealed a pattern of alphaAR subtype distribution that, while
      distinct from the gluteus maximus muscle, was consistent with that reported for
      the rat cremaster muscle. We conclude that functional alphaAR subtype
      distribution in arteriolar networks of skeletal muscle varies with muscle
      function as well as vessel branch order.

PMID- 20807786
TI  - The neural basis of visual attention.
AB  - Visual attention is the mechanism the nervous system uses to highlight specific
      locations, objects or features within the visual field. This can be accomplished
      by making an eye movement to bring the object onto the fovea (overt attention) or
      by increased processing of visual information in neurons representing more
      peripheral regions of the visual field (covert attention). This review will
      examine two aspects of visual attention: the changes in neural responses within
      visual cortices due to the allocation of covert attention; and the neural
      activity in higher cortical areas involved in guiding the allocation of
      attention. The first section will highlight processes that occur during visual
      spatial attention and feature-based attention in cortical visual areas and
      several related models that have recently been proposed to explain this activity.
      The second section will focus on the parietofrontal network thought to be
      involved in targeting eye movements and allocating covert attention. It will
      describe evidence that the lateral intraparietal area, frontal eye field and
      superior colliculus are involved in the guidance of visual attention, and
      describe the priority map model, which is thought to operate in at least several
      of these areas.

PMID- 20807787
TI  - Immunostaining for the alpha3 isoform of the Na+/K+-ATPase is selective for
      functionally identified muscle spindle afferents in vivo.
AB  - Muscle spindle afferent (MSA) neurons can show rapid and sustained firing.
      Immunostaining for the alpha3 isoform of the Na(+)/K(+)-ATPase (alpha3) in some
      large dorsal root ganglion (DRG) neurons and large intrafusal fibres suggested
      alpha3 expression in MSAs (Dobretsov et al. 2003), but not whether alpha3
      immunoreactive DRG neuronal somata were exclusively MSAs. We found that neuronal
      somata with high alpha3 immunointensity were neurofilament-rich, suggesting they
      have A-fibres; we therefore focussed on A-fibre neurons to determine the sensory
      properties of alpha3-immunoreactive neurons. We examined alpha3 immunointensity
      in 78 dye-injected DRG neurons whose conduction velocities and hindlimb sensory
      receptive fields were determined in vivo. A dense perimeter or ring of staining
      in a subpopulation of neurons was clearly overlying the soma membrane and not
      within satellite cells. Neurons with clear alpha3 rings (n = 23) were all MSAs
      (types I and II); all MSAs had darkly stained alpha3 rings, that tended to be
      darker in MSA1 than MSA2 units. Of 52 non-MSA A-fibre neurons including
      nociceptive and cutaneous low-threshold mechanoreceptive (LTM) neurons, 50 had no
      discernable ring, while 2 (Aalpha/beta cutaneous LTMs) had weakly stained rings.
      Three of three C-nociceptors had no rings. MSAs with strong ring immunostaining
      also showed the strongest cytoplasmic staining. These findings suggest that
      alpha3 ring staining is a selective marker for MSAs. The alpha3 isoform of the
      Na(+)/K(+)-ATPase has previously been shown to be activated by higher Na(+)
      levels and to have greater affinity for ATP than the alpha1 isoform (in all DRG
      neurons). The high alpha3 levels in MSAs may enable the greater dynamic firing
      range in MSAs.

PMID- 20807788
TI  - Redox modulation of the fetal cardiovascular defence to hypoxaemia.
AB  - Episodes of hypoxia in utero present a potentially serious challenge to the
      fetus, but are counteracted by defence responses including marked redistribution
      of blood flow from peripheral circulations to the brain. Here, we report the
      novel observation that the oxidant tone is an important modulator of this
      cardiovascular defence. Using pregnant Welsh Mountain sheep surgically prepared
      for long-term recording, we investigated in vivo the effects on the fetal
      cardiovascular defence to acute hypoxaemia of fetal treatment with the
      antioxidant vitamin C. The mechanisms via which vitamin C may affect the vascular
      oxidant tone were investigated by monitoring fetal plasma concentrations of
      nitrates and nitrites, by determining changes in the activity of superoxide
      dismutase (SOD) in fetal plasma, and by investigating the effect of vitamin C
      treatment on the fetal cardiovascular defence to hypoxaemia following nitric
      oxide (NO) synthase blockade. Fetal treatment with vitamin C markedly depressed
      the normal femoral constrictor response to acute hypoxaemia in the fetus (5.2 +/-
      1.0 vs. 1.1 +/- 0.3 mmHg (ml min(-1))(-1), mean +/- s.e.m.; P < 0.05) an effect
      which was completely restored following NO synthase blockade (6.2 +/- 1.3 mmHg
      (ml min(-1))(-1)). Compared to saline infusion, fetal treatment with vitamin C
      during acute hypoxaemia also significantly increased fetal plasma SOD activity
      from normoxic baseline (-8.9 +/- 6.5 vs. 15.0 +/- 6.6% inhibition, P < 0.05) and
      decreased the plasma concentration ratio of nitrate:nitrite from normoxic
      baseline (DeltaNO3(-):NO2(-); 0.15 +/- 0.30 vs. -0.29 +/- 0.11, P < 0.05). The
      data provide in vivo evidence of redox modulation of redistribution of blood flow
      in the fetus, part of the fetal brain sparing during acute hypoxaemic stress.

PMID- 20807789
TI  - Vasodilatory responsiveness to adenosine triphosphate in ageing humans.
AB  - Endothelium-dependent vasodilatation is reduced with advancing age in humans, as
      evidenced by blunted vasodilator responsiveness to acetylcholine (ACh).
      Circulating adenosine triphosphate (ATP) has been implicated in the control of
      skeletal muscle vascular tone during mismatches in oxygen delivery and demand
      (e.g. exercise) via binding to purinergic receptors (P2Y) on the endothelium
      evoking subsequent vasodilatation, and ageing is typically associated with
      reductions in muscle blood flow under such conditions. Therefore, we tested the
      hypothesis that ATP-mediated vasodilatation is impaired with age in healthy
      humans. We measured forearm blood flow (venous occlusion plethysmography) and
      calculated vascular conductance (FVC) responses to local intra-arterial infusions
      of ACh, ATP, and sodium nitroprusside (SNP) before and during ascorbic acid (AA)
      infusion in 13 young and 13 older adults. The peak increase in FVC to ACh was
      significantly impaired in older compared with young adults (262 +/- 71% vs. 618
      +/- 97%; P < 0.05), and this difference was abolished during AA infusion (510 +/-
      82% vs. 556 +/- 71%; not significant, NS). In contrast, peak FVC responses were
      not different between older and young adults to either ATP (675 +/- 105% vs. 734
      +/- 126%) or SNP (1116 +/- 111% vs. 1138 +/- 148%) and AA infusion did not alter
      these responses in either age group (both NS). In another group of six young and
      six older adults, we determined whether vasodilator responses to adenosine and
      ATP were influenced by P1-receptor blockade via aminophylline. The peak FVC
      responses to adenosine were not different in young (350 +/- 65%) versus older
      adults (360 +/- 80%), and aminophylline blunted these responses by ~50% in both
      groups. The peak FVC responses to ATP were again not different in young and older
      adults, and aminophylline did not impact the vasodilatation in either group.
      Thus, in contrast to the observed impairments in ACh responses, the vasodilatory
      response to exogenous ATP is not reduced with age in healthy humans. Further, our
      data also indicate that adenosine mediated vasodilatation is not reduced with
      age, and that ATP-mediated vasodilatation is independent of P1-receptor
      stimulation in both young and older adults.

PMID- 20807790
TI  - Lithium acts as a potentiator of AMPAR currents in hippocampal CA1 cells by
      selectively increasing channel open probability.
AB  - Recent evidence suggests that lithium, which is used in the treatment of bipolar
      disorders, may act by influencing AMPAR properties at central glutamatergic
      synapses. While it is clear that lithium potentiates recombinant AMPAR responses
      in a subunit specific way, the origin of this potentiation is not known. We
      examined the effects of lithium on native AMPAR channels in CA1 pyramidal cells
      in hippocampal slices where AMPARs are expected to be associated with auxiliary
      subunits. We found that lithium produced a selective increase in single-channel
      open probability (P(open)), with little effect on single-channel conductance or
      burst length. From the present and previous finding it is likely that lithium
      causes a reduction in the time to recovery from desensitization, resulting in the
      observed increase in P(open). This would be consistent with the view that lithium
      acts like certain other allosteric AMPAR modulators to reduce the time spent in
      the desensitized state, but differs from those that act by slowing dissociation
      of glutamate.

PMID- 20807792
TI  - Transient receptor potential vanilloid type-1 (TRPV-1) channels contribute to
      cutaneous thermal hyperaemia in humans.
AB  - The initial, rapid increase in skin blood flow in response to direct application
      of heat is thought to be mediated by an axon reflex, which is dependent on intact
      cutaneous sensory nerves. We tested the hypothesis that inhibition of transient
      receptor potential vanilloid type 1 (TRPV-1) channels, which are putative
      channels located on sensory nerves, would attenuate the skin blood flow response
      to local heating in humans. Ten subjects were equipped with four microdialysis
      fibres which were randomly assigned one of four treatments: (1) vehicle control
      (90% propylene glycol + 10% lactated Ringer solution); (2) 20 mm capsazepine to
      inhibit TRPV-1 channels; (3) 10 mm l-NAME to inhibit NO synthase; and (4)
      combined 20 mm capsazepine + 10 mm l-NAME. Following baseline measurements, the
      temperature of skin heaters was increased from 33 degrees C to 42 degrees C at a
      rate of 1.0 degrees C every 10 s and local temperature was held at 42 degrees C
      for 20-30 min until a stable plateau in skin blood flow was achieved. An index of
      skin blood flow was measured directly over each microdialysis site via laser
      Doppler flowmetry (LDF). Beat-by-beat blood pressure was measured via
      photoplethysmography and verified via automated brachial auscultation. At the end
      of the local heating protocol, temperature of the heaters was increased to 43
      degrees C and 28 mm nitroprusside was infused to achieve maximal vasodilatation.
      Cutaneous vascular conductance (CVC) was calculated as LDF/mean arterial pressure
      and normalized to maximal values (%CVCmax). Initial peak in capsazepine (44 +/-
      4%CVCmax), l-NAME (56 +/- 4%CVCmax) and capsazepine + l-NAME (32 +/- 6%CVCmax)
      sites was significantly attenuated compared to control (87 +/- 5%CVCmax; P <
      0.001 for all conditions). The plateau phase of thermal hyperaemia was
      significantly attenuated in capsazepine (73 +/- 6%CVCmax), l-NAME (47 +/-
      5%CVCmax) and capsazepine + l-NAME (31 +/- 7%CVCmax) sites compared to control
      (92 +/- 5%CVCmax; P < 0.001 for all conditions). These data suggest TRPV-1
      channels contribute substantially to the initial peak and modestly to the plateau
      phases of thermal hyperaemia. These data further suggest a portion of the NO
      component of thermal hyperaemia may be due to activation of TRPV-1 channels.

PMID- 20807791
TI  - Arterial stiffening with ageing is associated with transforming growth factor
      beta1-related changes in adventitial collagen: reversal by aerobic exercise.
AB  - We tested the hypothesis that carotid artery stiffening with ageing is associated
      with transforming growth factor-beta1 (TGF-beta1)-related increases in
      adventitial collagen and reductions in medial elastin, which would be reversed by
      voluntary aerobic exercise. Ex vivo carotid artery incremental stiffness was
      greater in old (29-32 months, n = 11) vs. young (4-7 months, n = 8) cage control
      B6D2F1 mice (8.84 +/- 1.80 vs. 4.54 +/- 1.18 AU, P < 0.05), and was associated
      with selective increases in collagen I and III and TGF-beta1 protein expression
      in the adventitia (P < 0.05), related to an increase in smooth muscle alpha-actin
      (SMalphaA) (myofibroblast phenotype) (P < 0.05). In cultured adventitial
      fibroblasts, TGF-beta1 induced increases in superoxide and collagen I protein (P
      < 0.05), which were inhibited by Tempol, a superoxide dismutase. Medial elastin
      was reduced with ageing, accompanied by decreases in the pro-synthetic elastin
      enzyme, lysyl oxidase, and increases in the elastin-degrading enzyme, matrix
      metalloproteinase 2. Fibronectin was unchanged with ageing, but there was a small
      increase in calcification (P < 0.05). Increased incremental stiffness in old mice
      was completely reversed (3.98 +/- 0.34 AU, n = 5) by 10-14 weeks of modest
      voluntary wheel running (1.13 +/- 0.29 km day-1), whereas greater voluntary wheel
      running (10.62 +/- 0.49 km day-1) had no effect on young mice. The amelioration
      of carotid artery stiffness by wheel running in old mice was associated with
      reductions in collagen I and III and TGF-beta1, partial reversal of the
      myofibroblast phenotype (reduced SMalphaA) and reduced calcification (all P <
      0.05 vs. old controls), whereas elastin and its modulating enzymes were
      unaffected. Adventitial TGF-beta1-related oxidative stress may play a key role in
      collagen deposition and large elastic artery stiffening with ageing and the
      efficacious effects of voluntary aerobic exercise.

PMID- 20807793
TI  - Coronary vasoconstrictor responses are attenuated in young women as compared with
      age-matched men.
AB  - Recent work in humans suggests coronary vasoconstriction occurs with static
      handgrip with a time course that suggests a sympathetic constrictor mechanism.
      These findings are consistent with animal studies that suggest this effect helps
      maintain transmural myocardial perfusion. It is known that oestrogen can
      attenuate sympathetic responsiveness, however it is not known if sympathetic
      constrictor responses vary in men and women. To examine this issue we studied
      young men (n = 12; 28 +/- 1 years) and women (n = 14; 30 +/- 1 years). Coronary
      blood flow velocity (CBV; Duplex Ultrasound), heart rate (ECG) and blood pressure
      (BP; Finapres) were measured during static handgrip (20 s) at 10% and 70% of
      maximum voluntary contraction. Measurements were also obtained during graded
      lower body negative pressure (LBNP; activates baroreflex-mediated sympathetic
      system) and the cold pressor test (CPT; a non-specific sympathetic stimulus). A
      coronary vascular resistance index (CVR) was calculated as diastolic BP/CBV.
      Increases in CVR with handgrip were greater in men vs. women (1.25 +/- 0.49 vs.
      0.26 +/- 0.38 units; P < 0.04) and CBV tended to fall in men but not in women (
      0.9 +/- 0.9 vs. 1.7 +/- 0.8 cm s-1; P < 0.01). Changes in CBV with handgrip were
      linked to the myocardial oxygen consumption in women but not in men. CBV
      reductions were greater in men vs. women during graded LBNP (P < 0.04). Men and
      women had similar coronary responses to CPT (P = n.s.). We conclude that coronary
      vasoconstrictor tone is greater in men than women during static handgrip and
      LBNP.

PMID- 20807794
TI  - Fast glutamate uptake via EAAT2 shapes the cone-mediated light offset response in
      bipolar cells.
AB  - Excitatory amino acid transporters (EAATs) are responsible for extracellular
      glutamate uptake within the retina, and are expressed by retinal neurons and
      Muller cells. Their role within glutamatergic synapses is not completely
      understood. In the salamander retina, five distinct EAAT-encoding genes have been
      cloned, making the amphibian retina an excellent system to study EAAT function.
      This study focused on sEAAT2, which is expressed in photoreceptor terminals and
      Off-bipolar cells in two isoforms, sEAAT2A and sEAAT2B. Using whole-cell patch
      clamp recording, florescence imaging and antibody labelling methods, we
      systematically studied the functions of these two isoforms at the synapse between
      photoreceptors and bipolar cells, both in dark and with photic stimulation. Both
      sEAAT2A and sEAAT2B were sensitive to dihydrokainic acid (DHKA), a known EAAT2
      specific inhibitor. Each isoform of sEAAT2 was found to play a role in tonic
      glutamate uptake at the cone synapse in darkness. Furthermore, presynaptic
      sEAAT2A strongly suppressed the rapid, transient glutamate signal from cones
      following light-offset. This was achieved by quickly binding exocytosed
      glutamate, which subsequently limited glutamate spillover to adjacent receptors
      at postsynaptic sites. Since the intensity and duration of photic stimulation
      determine the magnitude of these cone transient signals, we postulate that
      presynaptic cone EAATs contribute to the encoding of contrast sensitivity in cone
      vision.

PMID- 20807795
TI  - Orexin neurons are indispensable for stress-induced thermogenesis in mice.
AB  - Orexin neurons contribute to cardiovascular, respiratory and analgesic components
      of the fight-or-flight response against stressors. Here, we examined whether the
      same is true for stress-induced hyperthermia. We used prepro-orexin knockout mice
      (ORX-KO) and orexin neuron-ablated mice (ORX-AB) in which the latter lack not
      only orexin, but also other putative neurotransmitter/modulators contained in the
      orexin neurons. In response to repetitive insertion of a temperature probe into
      their rectum (handling stress), ORX-KO mice showed a normal temperature change as
      compared to that of wild-type littermates (WT) while ORX-AB showed an attenuated
      response. Stress-induced expression of uncoupling protein-1, a key molecule in
      non-shivering thermogenesis in the brown adipose tissue (BAT), was also blunted
      in ORX-AB but not in ORX-KO. When the BAT was directly activated by a beta3
      adrenergic agonist, there was no difference in the resultant BAT temperature
      among the groups, indicating that BAT per se was normal in ORX-AB. In WT and ORX
      KO, handling stress activated orexin neurons (as revealed by increased expression
      of c-Fos) and the resultant hyperthermia was largely blunted by pre-treatment
      with a beta3 antagonist. This observation further supports the notion that
      attenuated stress-induced hyperthermia in ORX-AB mice was caused by a loss of
      orexin neurons and abnormal BAT regulation. This study pointed out, for the first
      time, the possible importance of co-existent neurotransmitter/modulators in the
      orexin neurons for stress-induced hyperthermia and the importance of integrity of
      the orexin neurons for full expression of multiple facets of the fight-or-flight
      response.

PMID- 20807796
TI  - AT1 receptor and NAD(P)H oxidase mediate angiotensin II-stimulated antioxidant
      enzymes and mitogen-activated protein kinase activity in the rat hypothalamus.
AB  - INTRODUCTION: Angiotensin II (AngII) regulates blood pressure and water and
      electrolyte metabolism through the stimulation of NAD(P)H oxidase and production
      of reactive oxygen species (ROS) such as O2-, which is metabolised by superoxide
      dismutase, catalase and glutathione peroxidase. We assessed the role of AT1 and
      AT2 receptors, NAD(P)H oxidase and protein kinase C (PKC) in Ang II-induced
      sodium and water excretion and their capacity to stimulate antioxidant enzymes in
      the rat hypothalamus, a brain structure known to express a high density of AngII
      receptors. MATERIALS AND METHODS: Male Sprague-Dawley rats were
      intracerebroventricularly (ICV) injected with AngII and urinary sodium and water
      excretion was assessed. Urine sodium concentration was determined using flame
      photometry. After decapitation the hypothalamus was microdissected under
      stereomicroscopic control. Superoxide dismutase, catalase and glutathione
      peroxidase activity were determined spectrophotometrically and extracellular
      signal-regulated kinase (ERK1/2) activation was analysed by Western blot.
      RESULTS: AngII-ICV resulted in antidiuresis and natriuresis. ICV administration
      of losartan, PD123319, apocynin and chelerythrine blunted natriuresis. In
      hypothalamus, AngII increased catalase, superoxide dismutase and glutation
      peroxidase activity and ERK1/2 phosphorylation. These actions were prevented by
      losartan, apocynin and chelerythrine, and increased by PD123319. CONCLUSIONS: AT1
      and AT2 receptors, NAD(P)H oxidase and PKC pathway are involved in the regulation
      of hydromineral metabolism and antioxidant enzyme activity induced by AngII.

PMID- 20807797
TI  - Pathobiological aspects of the local bone marrow renin-angiotensin system: a
      review.
AB  - The local haematopoietic bone marrow (BM) renin-angiotensin system (RAS) mediates
      pathobiological alterations of haematopoiesis in an
      autocrine/paracrine/intracrine fashion. Recent data further indicated the
      existence of angiotensin-converting enzyme (ACE) in human primitive lympho
      haematopoietic cells, embryonic, foetal and adult haematopoietic tissues. Human
      umbilical cord blood cells also express renin, angiotensinogen, and ACE mRNAs. As
      ACE and other angiotensin peptides function in human haematopoietic stem cells
      (HSCs) throughout haematopoietic ontogeny and adulthood, local RAS could also
      have a function in HSC plasticity, and the development of haematological
      neoplastic disorders. The presence of ACE on leukaemic blast cells within
      leukaemic BM, on erythroleukaemic cells, ACE-expressing macrophages in lymph
      nodes of Hodgkin disease, renin activity in leukaemic blasts, angiotensin II as
      an autocrine growth factor for AML, increased renin gene activity during NUP98
      HOXA9 enhanced blast formation, higher levels of BB9/ACE (+) AML isoforms, and
      altered JAK-STAT pathway as a link between RAS and leukaemia indicated the wide
      pathobiological aspects of local BM RAS. The comparable biological actions of
      local RASs throughout the human body (including myocardium, pancreas, pituitary
      gland, ovary and kidney) represent the true basis for the search of their
      prominence in tissue functions. Recent data and perspectives of the local BM RAS
      in health and disease are reviewed in this paper.

PMID- 20807798
TI  - Developmental changes in AT1 and AT2 receptor-protein expression in rats.
AB  - It has long been known that angiotensin type-1 receptors (AT1R) play a critical
      role in sympathetic regulation, cardiovascular activity, and hormone secretion
      under physiological and pathological states. On the other hand, the functional
      significance of angiotensin type-2 receptors (AT2R) is poorly understood. In a
      recent study we demonstrated that, in rats with chronic heart failure, AT1R
      protein expression was increased but AT2R expression was decreased in the rostral
      ventrolateral medulla (RVLM). This imbalance of angiotensin receptors contributed
      to sympatho-excitation in the heart failure state. In the current experiment, we
      measured AT1R and AT2R protein expressions in the brainstem, kidney and liver
      from male foetuses (3 days before birth), male neonates (3 days after birth),
      male and female adults (8 weeks) and male aged (28 months) rats by Western blot
      analysis. In the brainstem, we found that the foetuses and neonates exhibited a
      significantly lower AT2R protein expression compared with adult rats (foetus 0.08
      +/- 0.01, neonate 0.12 +/- 0.01, male adult 0.25 +/- 0.01, female adult 0.22 +/-
      0.02; n = 4 per group, p < 0.001 foetus and neonate compared with male or female
      adults). In contrast, the foetuses and neonates expressed significantly higher
      AT1R protein than that of the adults (foetus 0.64 +/- 0.09, neonate 0.56 +/-
      0.01, male adult 0.13 +/- 0.02, female adult 0.08 +/- 0.02; n = 4 each group, p <
      0.001 foetus and neonate compared with male and female adults). In the liver, the
      AT2R protein was also higher in foetus and neonate, than in adult rats.
      Interestingly, the foetal liver expressed higher AT1R protein compared with that
      of the neonate. In the kidney, AT2R expression was significantly increased with
      age (foetus 0.08 +/- 0.01, neonate 0.19 +/- 0.02, male adult 0.49 +/- 0.04,
      female adult 0.90 +/- 0.10; n = 4 per group, p < 0.01-0.001). AT1R expression, on
      the other hand, was higher in the foetuses than that in both neonate and male
      adults. This study provides data contrary to existing dogma that AT2R expression
      is higher in foetal life and low in adults, suggesting an involvement of a
      potentially important functional role for AT2R in adult animals and AT1R in
      foetal development and/or physiology.

PMID- 20807799
TI  - The recruitment of acetylated and unacetylated tropomyosin to distinct actin
      polymers permits the discrete regulation of specific myosins in fission yeast.
AB  - Tropomyosin (Tm) is a conserved dimeric coiled-coil protein, which forms polymers
      that curl around actin filaments in order to regulate actomyosin function.
      Acetylation of the Tm N-terminal methionine strengthens end-to-end bonds, which
      enhances actin binding as well as the ability of Tm to regulate myosin motor
      activity in both muscle and non-muscle cells. In this study we explore the
      function of each Tm form within fission yeast cells. Electron microscopy and live
      cell imaging revealed that acetylated and unacetylated Tm associate with distinct
      actin structures within the cell, and that each form has a profound effect upon
      the shape and integrity of the polymeric actin filament. We show that, whereas Tm
      acetylation is required to regulate the in vivo motility of class II myosins,
      acetylated Tm had no effect on the motility of class I and V myosins. These
      findings illustrate a novel Tm-acetylation-state-dependent mechanism for
      regulating specific actomyosin cytoskeletal interactions.

PMID- 20807801
TI  - NuSAP is essential for chromatin-induced spindle formation during early
      embryogenesis.
AB  - Mitotic spindle assembly is mediated by two processes: a centrosomal and a
      chromosomal pathway. RanGTP regulates the latter process by releasing microtubule
      associated proteins from inhibitory complexes. NuSAP, a microtubule- and DNA
      binding protein, is a target of RanGTP and promotes the formation of microtubules
      near chromosomes. However, the contribution of NuSAP to cell proliferation in
      vivo is unknown. Here, we demonstrate that the expression of NuSAP highly
      correlates with cell proliferation during embryogenesis and adult life, making it
      a reliable marker of proliferating cells. Additionally, we show that NuSAP
      deficiency in mice leads to early embryonic lethality. Spindle assembly in NuSAP
      deficient cells is highly inefficient and chromosomes remain dispersed in the
      mitotic cytoplasm. As a result of sustained spindle checkpoint activity, the
      cells are unable to progress through mitosis, eventually leading to caspase
      activation and apoptotic cell death. Together, our findings demonstrate that
      NuSAP is essential for proliferation of embryonic cells and, simultaneously, they
      underscore the importance of chromatin-induced spindle assembly.

PMID- 20807800
TI  - The exocytic gene secA is required for Dictyostelium cell motility and
      osmoregulation.
AB  - We investigated the link between cell movement and plasma membrane recycling
      using a fast-acting, temperature-sensitive mutant of the Dictyostelium SecA
      exocytic protein. Strikingly, most mutant cells become almost paralysed within
      minutes at the restrictive temperature. However, they can still sense cyclic-AMP
      (cAMP) gradients and polymerise actin up-gradient, but form only abortive
      pseudopodia, which cannot expand. They also relay a cAMP signal normally,
      suggesting that cAMP is released by a non-exocytic mechanism. To investigate why
      SecA is required for motility, we examined membrane trafficking in the mutant.
      Plasma membrane circulation is rapidly inhibited at the restrictive temperature
      and the cells acquire a prominent vesicle. Organelle-specific markers show that
      this is an undischarged contractile vacuole, and we found the cells are
      correspondingly osmo-sensitive. Electron microscopy shows that many smaller
      vesicles, probably originating from the plasma membrane, also accumulate at the
      restrictive temperature. Consistent with this, the surface area of mutant cells
      shrinks. We suggest that SecA mutant cells cannot move at the restrictive
      temperature because their block in exocytosis results in a net uptake of plasma
      membrane, reducing its area, and so restricting pseudopodial expansion. This
      demonstrates the importance of proper surface area regulation in cell movement.

PMID- 20807802
TI  - Golgi-associated GSK3beta regulates the sorting process of post-Golgi membrane
      trafficking.
AB  - Glycogen synthase kinase beta (GSK3beta) phosphorylates many substrates in
      mammalian cells, and functions in many physiological processes. We observed that
      GSK3beta knockdown by siRNA perturbed both Golgi morphology in HeLa cells and the
      anterograde transport of cation-independent mannose 6-phosphate receptor (CI
      M6PR) from the trans-Golgi network (TGN) to prelysosomal compartments (PLC),
      diverting it to the exocytic pathway. Moreover, we demonstrate that a portion of
      GSK3beta was localized to the TGN through the Golgi peripheral protein p230 and
      that this localization regulated CLASP2 phosphorylation. Our results also show
      that GSK3beta knockdown resulted in accumulation of CLASP2 at microtubule plus
      ends at the cell periphery. Our findings support the hypothesis that GSK3beta at
      the TGN acts as a guide, activates exocytic transport, and redirects CI-M6PR from
      transport to the PLC into the exocytic pathway by regulating the affinity of
      CLASPs for microtubules.

PMID- 20807803
TI  - The RB-E2F1 pathway regulates autophagy.
AB  - Autophagy is a protective mechanism that renders cells viable in stressful
      conditions. Emerging evidence suggests that this cellular process is also a tumor
      suppressor pathway. Previous studies showed that cyclin-dependent kinase
      inhibitors (CDKI) induce autophagy. Whether retinoblastoma protein (RB), a key
      tumor suppressor and downstream target of CDKIs, induces autophagy is not clear.
      Here, we show that RB triggers autophagy and that the RB activators p16INK4a and
      p27/kip1 induce autophagy in an RB-dependent manner. RB binding to E2
      transcription factor (E2F) is required for autophagy induction and E2F1
      antagonizes RB-induced autophagy, leading to apoptosis. Downregulation of E2F1 in
      cells results in high levels of autophagy. Our findings indicate that RB induces
      autophagy by repressing E2F1 activity. We speculate that this newly discovered
      aspect of RB function is relevant to cancer development and therapy.

PMID- 20807804
TI  - Modulation of gene expression and tumor cell growth by redox modification of
      STAT3.
AB  - Reactive oxygen species (ROS) promote tumor cell proliferation and survival by
      directly modulating growth-regulatory molecules and key transcription factors.
      The signal transducer and activator of transcription 3 (STAT3) is constitutively
      active in a variety of tumor cell types, where the effect of ROS on the Janus
      kinase/STAT pathway has been examined. We report here that STAT3 is directly
      sensitive to intracellular oxidants. Oxidation of conserved cysteines by peroxide
      decreased STAT3 binding to consensus serum-inducible elements (SIE) in vitro and
      in vivo and diminished interleukin (IL)-6-mediated reporter expression.
      Inhibitory effects produced by cysteine oxidation in STAT3 were negated in redox
      insensitive STAT3 mutants. In contrast, ROS had no effect on IL-6-induced STAT3
      recruitment to the c-myc P2 promoter. Expression of a redox-insensitive STAT3 in
      breast carcinoma cells accelerated their proliferation while reducing resistance
      to oxidative stress. Our results implicate STAT3 in coupling intracellular redox
      homeostasis to cell proliferation and survival.

PMID- 20807805
TI  - Survivin enhances motility of melanoma cells by supporting Akt activation and
      {alpha}5 integrin upregulation.
AB  - Survivin expression in melanoma is inversely correlated with patient survival.
      Transgenic mice harboring melanocyte-specific overexpression of survivin exhibit
      increased susceptibility to UV-induced melanoma and metastatic progression. To
      understand the mechanistic basis for metastatic progression, we investigated the
      effects of survivin on the motility of human melanocytes and melanoma cells. We
      found that survivin overexpression enhanced migration on fibronectin and invasion
      through Matrigel, whereas survivin knockdown under subapoptotic conditions
      blocked migration and invasion. In melanocytes, survivin overexpression activated
      the Akt and mitogen-activated protein kinase pathways. Akt phosphorylation was
      required for survivin-enhanced migration and invasion, whereas Erk
      phosphorylation was required only for enhanced invasion. In both melanocytes and
      melanoma cells, survivin overexpression was associated with upregulation of
      alpha5 integrin (fibronectin receptor component), the antibody-mediated blockade
      or RNA interference-mediated knockdown of which blocked survivin-enhanced
      migration. Knockdown of alpha5 integrin did not affect Akt activation, but
      inhibition of Akt phosphorylation prevented alpha5 integrin upregulation elicited
      by survivin overexpression. Together, our results showed that survivin enhanced
      the migration and invasion of melanocytic cells and suggested that survivin may
      promote melanoma metastasis by supporting Akt-dependent upregulation of alpha5
      integrin.

PMID- 20807806
TI  - Amplifying TLR-MyD88 signals within tumor-specific T cells enhances antitumor
      activity to suboptimal levels of weakly immunogenic tumor antigens.
AB  - The efficacy of T cell-based immunotherapy to treat cancer patients remains a
      challenge partly because of the weak activity toward subdominant tumor antigens
      (TAg) and to tumors expressing suboptimal TAg levels. Recent reports indicate
      that Toll-like receptor (TLR) stimulation on T cells can lower the activation
      threshold. In this study, we examined the antitumor activity and survival of TLR2
      MyD88-stimulated CD8 T cells derived from melanoma patients and T-cell receptor
      transgenic pmel mice. TLR2-stimulated pmel CD8 T cells, but not TLR2(-/-)pmel or
      MyD88(-/-)pmel T cells, responded to significantly lower TAg levels and resulted
      in increased production of effector molecules and cytotoxicity. Wild-type or
      MyD88(-/-) mice treated with TLR2 ligand and pmel T cells, but not TLR2(-/-)pmel
      or MyD88(-/-)pmel T cells, showed tumor regression of an established melanoma
      tumor. Overexpressing TLR2 in TAg-specific T cells eradicated tumors; four times
      fewer cells were needed to generate antitumor responses. The enhanced antitumor
      activity of TLR2-MyD88-stimulated T cells was associated with increased effector
      function but perhaps more importantly with improved survival of T cells.
      Activating TLR-MyD88 signals in patient-derived T cells also reduced the
      activation threshold to several weakly immunogenic TAgs, resulting in increased
      cytokine production, expansion, and cytotoxicity. These data highlight a
      previously unappreciated role for activating TLR-MyD88 signals in tumor-reactive
      T lymphocytes.

PMID- 20807807
TI  - A novel, selective, and efficacious nanomolar pyridopyrazinone inhibitor of
      V600EBRAF.
AB  - Oncogenic BRAF is a critical driver of proliferation and survival and is thus a
      validated therapeutic target in cancer. We have developed a potent inhibitor,
      termed 1t (CCT239065), of the mutant protein kinase, (V600E)BRAF. 1t inhibits
      signaling downstream of (V600E)BRAF in cancer cells, blocking DNA synthesis, and
      inhibiting proliferation. Importantly, we show that 1t is considerably more
      selective for mutated BRAF cancer cell lines compared with wild-type BRAF lines.
      The inhibitor is well tolerated in mice and exhibits excellent oral
      bioavailability (F = 71%). Suppression of (V600E)BRAF-mediated signaling in human
      tumor xenografts was observed following oral administration of a single dose of
      1t. As expected, the growth rate in vivo of a wild-type BRAF human tumor
      xenograft model is unaffected by inhibitor 1t. In contrast, 1t elicits
      significant therapeutic responses in mutant BRAF-driven human melanoma
      xenografts.

PMID- 20807809
TI  - Nucleotide excision repair gene expression after Cisplatin treatment in melanoma.
AB  - Two of the hallmark features of melanoma are its development as a result of
      chronic UV radiation exposure and the limited efficacy of cisplatin in the
      disease treatment. Both of these DNA-damaging agents result in large helix
      distorting DNA damage that is recognized and repaired by nucleotide excision
      repair (NER). The aim of this study was to examine the expression of NER gene
      transcripts, p53, and p21 in melanoma cell lines treated with cisplatin compared
      with melanocytes. Basal expression of all genes was greater in the melanoma cell
      lines compared with melanocytes. Global genome repair (GGR) transcripts showed
      significantly decreased relative expression (RE) in melanoma cell lines 24 hours
      after cisplatin treatment. The basal RE of p53 was significantly higher in the
      melanoma cell lines compared with the melanocytes. However, induction of p53 was
      only significant in the melanocytes at 6 and 24 hours after cisplatin treatment.
      Inhibition of p53 expression significantly decreased the expression of all the
      GGR transcripts in melanocytes at 6 and 24 hours after cisplatin treatment.
      Although the RE levels were lower with p53 inhibition, the induction of the GGR
      genes was very similar to that in the control melanocytes and increased
      significantly across the time points. The findings from this study revealed
      reduced GGR transcript levels in melanoma cells 24 hours after cisplatin
      treatment. Our findings suggest a possible mechanistic explanation for the
      limited efficacy of cisplatin treatment and the possible role of UV light in
      melanoma.

PMID- 20807808
TI  - Tubulin-targeting chemotherapy impairs androgen receptor activity in prostate
      cancer.
AB  - Recent insights into the regulation of the androgen receptor (AR) activity led to
      novel therapeutic targeting of AR function in prostate cancer patients. Docetaxel
      is an approved chemotherapy for treatment of castration-resistant prostate
      cancer; however, the mechanism underlying the action of this tubulin-targeting
      drug is not fully understood. This study investigates the contribution of
      microtubules and the cytoskeleton to androgen-mediated signaling and the
      consequences of their inhibition on AR activity in human prostate cancer. Tissue
      microarrays from docetaxel-treated and untreated prostate cancer patients were
      comparatively analyzed for prostate-specific antigen (PSA) and AR
      immunoreactivity. The AR transcriptional activity was determined in prostate
      cancer cells in vitro, based on PSA mRNA expression and the androgen response
      element reporter activity. The interaction of AR with tubulin was examined by
      immunoprecipitation and immunofluorescence. Treatment of prostate cancer patients
      with docetaxel led to a significant translocation of AR. In untreated specimens,
      50% prostate tumor cells exhibited nuclear accumulation of AR, compared with
      docetaxel-treated tumors that had significantly depleted nuclear AR (38%),
      paralleled by an increase in cytosolic AR. AR nuclear localization correlated
      with PSA expression. In vitro, exposure of prostate cancer cells to paclitaxel (1
      MUmol/L) or nocodazole (5 MUg/mL) inhibited androgen-dependent AR nuclear
      translocation by targeting AR association with tubulin. Introduction of a
      truncated AR indicated the requirement of the NH(2)-terminal domain for AR
      tubulin interaction. Our findings show that in addition to blocking cell
      division, docetaxel impairs AR signaling, evidence that enables new insights into
      the therapeutic efficacy of microtubule-targeting drugs in prostate cancer.

PMID- 20807810
TI  - hnRNP A2/B1 modulates epithelial-mesenchymal transition in lung cancer cell
      lines.
AB  - Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) has been reported to
      be overexpressed in lung cancer and in other cancers such as breast, pancreas,
      and liver. However, a mechanism linking hnRNP A2/B1 overexpression and
      progression to cancer has not yet been definitively established. To elucidate
      this mechanism, we have silenced hnRNPA2/B1 mRNA in non-small-cell lung cancer
      cell lines A549, H1703, and H358. These cell lines present different levels of
      expression of epithelial-to-mesenchymal transition (EMT) markers such as E
      cadherin, fibronectin, and vimentin. Microarray expression analysis was performed
      to evaluate the effect of silencing hnRNP A2/B1 in A549 cells. We identified a
      list of target genes, affected by silencing of hnRNP A2/B1, that are involved in
      regulation of migration, proliferation, survival, and apoptosis. Silencing hnRNP
      A2/B1 induced formation of cell clusters and increased proliferation. In the
      anchorage-independent assay, silencing hnRNP A2/B1 increased colony formation by
      794% in A549 and 174% in H1703 compared with a 25% increase in proliferation, in
      both cell lines, in a two-dimensional proliferation assay. Silencing hnRNP A2/B1
      decreased migration in intermediate cell line A549 and mesenchymal cell line
      H1703; however, no changes in proliferation were observed in epithelial cell line
      H358. Silencing hnRNP A2/B1 in A549 and H1703 cells correlated with an increase
      of E-cadherin expression and downregulation of the E-cadherin inhibitors Twist1
      and Snai1. These data suggest that expression of hnRNP A2/B1 may play a role in
      EMT, in nonepithelial lung cancer cell lines A549 and H1703, through the
      regulation of E-cadherin expression.

PMID- 20807811
TI  - Differential mechanisms of acquired resistance to insulin-like growth factor-i
      receptor antibody therapy or to a small-molecule inhibitor, BMS-754807, in a
      human rhabdomyosarcoma model.
AB  - Agents targeting insulin-like growth factor-I receptor (IGF-IR), including
      antibodies and small-molecule inhibitors, are currently in clinical development
      for the treatment of cancers including sarcoma. However, development of
      resistance is a common phenomenon resulting in failures of anticancer therapies.
      In light of this problem, we developed two resistant models from the
      rhabdomyosarcoma cell line Rh41: Rh41-807R, with acquired resistance to BMS
      754807, a small-molecule dual-kinase inhibitor targeting IGF-IR and insulin
      receptor (IR), and Rh41-MAB391R, with resistance to MAB391, an IGF-IR-blocking
      antibody. In addition, tumor xenograft models were established from Rh41 and Rh41
      807R cell lines. Gene expression and DNA copy number analyses of these models
      revealed shared as well as unique acquired resistance mechanisms for the two
      types of IGF-IR inhibitors. Each resistant model used different signaling
      pathways as a mechanism for proliferation. Platelet-derived growth factor
      receptor alpha (PDGFRalpha) was amplified, overexpressed, and constitutively
      activated in Rh41-807R cells and tumors. Knockdown of PDGFRalpha by small
      interfering RNA in Rh41-807R resensitized the cells to BMS-754807. Synergistic
      activities were observed when BMS-754807 was combined with PDGFRalpha inhibitors
      in the Rh41-807R model in vitro. In contrast, AXL expression was highly elevated
      in Rh41-MAB391R but downregulated in Rh41-807R. Notably, BMS-754807 was active in
      Rh41-MAB391R cells and able to overcome resistance to MAB391, but MAB391 was not
      active in Rh41-807R cells, suggesting potentially broader clinical activity of
      BMS-754807. This is the first study to define and compare acquired resistance
      mechanisms for IGF-IR-targeted therapies. It provides insights into the
      differential acquired resistance mechanisms for IGF-IR/IR small-molecule
      inhibitor versus anti-IGF-IR antibody.

PMID- 20807812
TI  - PTEN loss accelerates KrasG12D-induced pancreatic cancer development.
AB  - KRAS mutations are found in ~90% of human pancreatic ductal adenocarcinomas
      (PDAC). However, mice genetically engineered to express Kras(G12D) from its
      endogenous locus develop PDACs only after a prolonged latency, indicating that
      other genetic events or pathway alterations are necessary for PDAC progression.
      The PTEN-controlled phosphatidylinositol 3-kinase (PI3K)/AKT signaling axis is
      dysregulated in later stages of PDAC. To better elucidate the role of
      PTEN/PI3K/AKT signaling in Kras(G12D)-induced PDAC development, we crossed Pten
      conditional knockout mice (Pten(lox/lox)) to mice with conditional activation of
      Kras(G12D). The resulting compound heterozygous mutant mice showed significantly
      accelerated development of acinar-to-ductal metaplasia (ADM), malignant
      pancreatic intraepithelial neoplasia (mPanIN), and PDAC within a year. Moreover,
      all mice with Kras(G12D) activation and Pten homozygous deletion succumbed to
      cancer by 3 weeks of age. Our data support a dosage-dependent role for PTEN, and
      the resulting dysregulation of the PI3K/AKT signaling axis, in both PDAC
      initiation and progression, and shed additional light on the signaling mechanisms
      that lead to the development of ADM and subsequent mPanIN and pancreatic cancer.

PMID- 20807813
TI  - A specific need for CRKL in p210BCR-ABL-induced transformation of mouse
      hematopoietic progenitors.
AB  - CRKL (CRK-like) is an adapter protein predominantly phosphorylated in cells that
      express the tyrosine kinase p210(BCR-ABL), the fusion product of a (9;22)
      chromosomal translocation causative for chronic myeloid leukemia. It has been
      unclear, however, whether CRKL plays a functional role in p210(BCR-ABL)
      transformation. Here, we show that CRKL is required for p210(BCR-ABL) to support
      interleukin-3-independent growth of myeloid progenitor cells and long-term
      outgrowth of B-lymphoid cells from fetal liver-derived hematopoietic progenitor
      cells. Furthermore, a synthetic phosphotyrosyl peptide that binds to the CRKL SH2
      domain with high affinity blocks association of endogenous CRKL with the p210(BCR
      ABL) complex and reduces c-MYC levels in K562 human leukemic cells as well as in
      mouse hematopoietic cells transformed by p210(BCR-ABL) or the imatinib-resistant
      mutant T315I. These results indicate that the function of CRKL as an adapter
      protein is essential for p210(BCR-ABL)-induced transformation.

PMID- 20807814
TI  - Cancer-associated fibroblasts enhance the gland-forming capability of prostate
      cancer stem cells.
AB  - Signals originating from cancer-associated fibroblasts (CAF) may positively
      regulate proliferation and tumorigenicity in prostate cancer. In this study, we
      investigated whether CAFs may regulate the biology of prostate cancer stem cells
      (CSC) by using a conditional Pten deletion mouse model of prostate adenocarcinoma
      to isolate both CAF cultures and CSC-enriched cell fractions from the tumors.
      CSCs that were isolated possessed self-renewal, spheroid-forming, and
      multipotential differentiation activities in tissue culture, segregating with a
      cell fraction exhibiting a signature expression phenotype, including SCA-1
      (high), CD49f (high), CK5 (high), p63 (high), Survivin (high), RUNX2 (high), CD44
      (low), CD133 (low), CK18 (low), and Androgen Receptor (low). CSC spheroid-forming
      efficiency was differentially influenced by the nature of fibroblasts in a
      coculture system: Compared with mouse urogenital sinus mesenchyme or normal
      prostate fibroblasts, CAFs enhanced spheroid formation, with the spheroids
      displaying generally larger sizes and more complex histology. Graft experiments
      showed that CSCs admixed with CAFs produced prostatic glandular structures with
      more numerous lesions, high proliferative index, and tumor-like histopathologies,
      compared with those formed in the presence of normal prostate fibroblasts.
      Together, our findings underscore a significant role of CAFs in CSC biology.

PMID- 20807815
TI  - Cyclin-dependent kinase-mediated phosphorylation plays a critical role in the
      oncogenic functions of PELP1.
AB  - Estrogen receptor (ER) signaling plays an important role in breast cancer
      progression, and ER functions are influenced by coregulatory proteins. PELP1
      (proline-, glutamic acid-, and leucine-rich protein 1) is a nuclear receptor
      coregulator that plays an important role in ER signaling. Its expression is
      deregulated in hormonal cancers. We identified PELP1 as a novel cyclin-dependent
      kinase (CDK) substrate. Using site-directed mutagenesis and in vitro kinase
      assays, we identified Ser(477) and Ser(991) of PELP1 as CDK phosphorylation
      sites. Using the PELP1 Ser(991) phospho-specific antibody, we show that PELP1 is
      hyperphosphorylated during cell cycle progression. Model cells stably expressing
      the PELP1 mutant that lack CDK sites had defects in estradiol (E2)-mediated cell
      cycle progression and significantly affected PELP1-mediated oncogenic functions
      in vivo. Mechanistic studies showed that PELP1 modulates transcription factor
      E2F1 transactivation functions, that PELP1 is recruited to pRb/E2F target genes,
      and that PELP1 facilitates ER signaling cross talk with cell cycle machinery. We
      conclude that PELP1 is a novel substrate of interphase CDKs and that its
      phosphorylation is important for the proper function of PELP1 in modulating
      hormone-driven cell cycle progression and also for optimal E2F transactivation
      function. Because the expression of both PELP1 and CDKs is deregulated in breast
      tumors, CDK-PELP1 interactions will have implications in breast cancer
      progression.

PMID- 20807816
TI  - The promise of microRNA replacement therapy.
AB  - MicroRNAs (miRNA), a class of natural RNA-interfering agents, have recently been
      identified as attractive targets for therapeutic intervention. The rationale for
      developing miRNA therapeutics is based on the premise that aberrantly expressed
      miRNAs play key roles in the development of human disease, and that correcting
      these miRNA deficiencies by either antagonizing or restoring miRNA function may
      provide a therapeutic benefit. Although miRNA antagonists are conceptually
      similar to other inhibitory therapies, restoring the function of a miRNA by miRNA
      replacement is a less well characterized approach. Here, we discuss the specific
      properties of miRNA replacement and review recent examples that explored the
      therapeutic delivery of miRNA mimics in animal models of cancer.

PMID- 20807817
TI  - BRCA1-associated epigenetic regulation of p73 mediates an effector pathway for
      chemosensitivity in ovarian carcinoma.
AB  - The majority of tumors arising in BRCA1 mutation carriers exhibit inactivation of
      p53, a key effector of cell death after DNA damage. Despite the loss of p53,
      BRCA1-deficient tumor cells exhibit increased sensitivity to cisplatin, and
      patients with BRCA1-associated ovarian carcinomas experience improved outcomes
      with platinum-based chemotherapy compared with sporadic cases. Although it is
      known that chemosensitivity in BRCA1-associated cancers is associated with
      unrepaired DNA damage, the specific effector pathway mediating the cellular
      response to platinum-induced damage in these tumors is poorly understood. Here,
      we show that the p53-related gene p73, encoding a proapoptotic protein that is
      linked to chemosensitivity in many settings, is upregulated through a novel
      epigenetic mechanism in both human and murine models of BRCA1-associated ovarian
      carcinoma. BRCA1-deficient ovarian carcinoma cells exhibit hypermethylation
      within a p73 regulatory region, which includes the binding site for the p73
      transcriptional repressor ZEB1, leading to the abrogation of ZEB1 binding and
      increased expression of transactivating p73 isoforms (TAp73). Cisplatin
      chemotherapy induces TAp73 target genes specifically in BRCA1-deficient cells,
      and knockdown of TAp73 in these cells causes chemoresistance while having little
      or no effect on BRCA1-expressing tumor cells. In primary ovarian carcinomas, ZEB1
      binding site methylation and TAp73 expression correlate with BRCA1 status and
      with clinical response. Together, these findings uncover a novel regulatory
      mechanism that supports the contribution of TAp73 as an important mediator of the
      response to platinum chemotherapy in a subset of ovarian carcinomas. TAp73 might
      represent a response predictor and potential therapeutic target for enhancing
      chemosensitivity in this disease.

PMID- 20807818
TI  - Using the transcription factor inhibitor of DNA binding 1 to selectively target
      endothelial progenitor cells offers novel strategies to inhibit tumor
      angiogenesis and growth.
AB  - Tumor angiogenesis is essential for malignant growth and metastasis. Bone marrow
      (BM)-derived endothelial progenitor cells (EPC) contribute to angiogenesis
      mediated tumor growth. EPC ablation can reduce tumor growth; however, the lack of
      a marker that can track EPCs from the BM to tumor neovasculature has impeded
      progress in understanding the molecular mechanisms underlying EPC biology. Here,
      we report the use of transgenic mouse and lentiviral models to monitor the BM
      derived compartment of the tumor stroma; this approach exploits the selectivity
      of the transcription factor inhibitor of DNA binding 1 (Id1) for EPCs to track
      EPCs in the BM, blood, and tumor stroma, as well as mature EPCs. Acute ablation
      of BM-derived EPCs using Id1-directed delivery of a suicide gene reduced
      circulating EPCs and yielded significant defects in angiogenesis-mediated tumor
      growth. Additionally, use of the Id1 proximal promoter to express microRNA-30
      based short hairpin RNA inhibited the expression of critical EPC-intrinsic
      factors, confirming that signaling through vascular endothelial growth factor
      receptor 2 is required for EPC-mediated tumor biology. By exploiting the
      selectivity of Id1 gene expression in EPCs, our results establish a strategy to
      track and target EPCs in vivo, clarifying the significant role that EPCs play in
      BM-mediated tumor angiogenesis.

PMID- 20807819
TI  - CRLF2 and JAK2 in B-progenitor acute lymphoblastic leukemia: a novel association
      in oncogenesis.
AB  - Expression of cytokine receptor-like factor 2 (CRLF2) has recently been shown to
      be upregulated as well as mutated in populations of B-progenitor acute
      lymphoblastic leukemia (B-ALL), including Down syndrome (DS-ALL) patients,
      lacking recurring chromosomal translocations. Increased CRLF2 expression
      associates with JAK2 mutation, a combination that transforms hematopoietic cells,
      suggesting that mutant JAK2 and CRLF2 may cooperate to contribute to B-ALL
      formation. Importantly, elevated CRLF2 expression correlates with poor outcome in
      high-risk B-ALL patients. Therefore, CRLF2 may provide a new prognostic marker
      for high-risk B-ALL, and inhibition of CRLF2/JAK2 signaling may represent a
      therapeutic approach for this population of ALL patients.

PMID- 20807820
TI  - Lymphocytic adenohypophysitis and adrenalitis in a dog with adrenal and thyroid
      atrophy.
AB  - A 4.5-year-old spayed female Great Pyrenees with hypothyroidism and
      hypoadrenocorticism had a slightly enlarged pituitary gland and bilaterally
      atrophic adrenal and thyroid glands. Lymphocytic adenohypophysitis and
      adrenalitis were found in which B lymphocytes and plasma cells dominated the
      adenohypophysitis but T cells dominated the adrenalitis. The thyroid gland had
      extensive follicular atrophy and collapse. The combination of primary
      hypothyroidism and hypoadrenocorticism resembles type II autoimmune polyendocrine
      syndrome or Schmidt syndrome in humans. Adenohypophysitis is rare in dogs and not
      reported in polyendocrine disease in animals.

PMID- 20807821
TI  - Multicentric fibromyxoid peripheral nerve sheath tumor (multicentric schwannoma)
      in a dromedary camel (Camelus dromedarius): morphopathological,
      immunohistochemical, and electron microscopic studies.
AB  - During postslaughter inspection of a 4-year-old male dromedary camel (Camelus
      dromedarius), numerous small nodules to large masses up to 4 cm in diameter were
      found on the serosal surfaces of forestomachs, large intestines, mesentery,
      liver, and spleen. Grossly, the masses were discrete, round, smooth, and white to
      gray that bulged from the serosal layer. Cut surfaces of the masses were
      discrete, round, white, and relatively homogeneous without any necrotic foci.
      Histopathologically, the masses were encapsulated and composed of a mixture of
      round and spindle-shaped cells in loose whorls of neoplastic cells with small
      elongated hyperchromatic wavy nuclei and a small amount of pale eosinophilic,
      poorly defined cytoplasm. Masson's trichrome staining showed mild amounts of
      collagen fibers forming an irregular, loose stroma. In immunohistochemistry,
      immunoreactivity for the Schwann cell marker (S100) was diffusely positive in the
      neoplastic cells. The immunoreactivity for CK, c-kit, and CD34 were negative.
      Ultrastructural examination confirmed the tumor was entirely formed of neoplastic
      Schwann cells. On the basis of the histopathological, immunohistochemical, and
      ultrastructural findings, the tumors were diagnosed as multicentric fibromyxoid
      peripheral nerve sheath tumor (multicentric schwannoma). This tumor has not been
      previously recorded in camel worldwide.

PMID- 20807822
TI  - Estradiol regulates expression of polysialated neural cell adhesion molecule by
      human vascular endothelial cells.
AB  - RATIONALE: The mechanism of atherogenesis includes leukocyte adhesion to
      endothelial cells followed by migration into the subendothelial space. The
      polysialylated neural cell adhesion molecules (PSA-nCAMs) are a group of
      hydrophilic neural cell adhesion molecule (NCAM) isoforms that inhibit NCAM: NCAM
      association, thereby blocking cell: cell adhesion. During previous studies, we
      demonstrated that sialylation of specific NCAMs are upregulated at proestrus in
      the rat and that PSA-nCAM is expressed by the rat vascular endothelium. METHODS
      AND RESULTS: In this study, we sought the presence of PSA-nCAM in human vessels
      and regulation of its expression in estradiol-treated human umbilical vascular
      endothelial cells (HUVEC). Immunoreactive PSA-nCAM (ir-PSA-nCAM) was shown in
      blood and lymph vessels of adult rats and human brain, skin, liver, lung, cervix,
      endometrium, and ovary. Staining for ir-PSA-nCAM was present on the glycocalyceal
      surface of estradiol-treated HUVEC, but not in the presence of the estrogen
      receptor (ER)-blocker fulvestrant. Western blotting confirmed these findings.
      CONCLUSIONS: PSA-nCAM is widely present in the glycocalyx of human and rat
      vascular endothelium. It also is expressed by HUVEC, in which it is induced by
      estradiol. The estrogen-regulated presence of vascular PSA-nCAM could diminish
      NCAM-dependent interactions between vessels and circulating leukocytes, thereby
      impeding vascular inflammation and atherogenesis, and, contributing to estrogen
      induced cardioprotection. This hypothesized action is presently under study.

PMID- 20807824
TI  - Guest editorial: special focus on the pathology of biological select agents and
      toxins in animals and research challenges in biological defense.

PMID- 20807825
TI  - Aerosol exposure to the angola strain of marburg virus causes lethal viral
      hemorrhagic Fever in cynomolgus macaques.
AB  - Cynomolgus macaques were exposed to the Angola strain of Lake Victoria Marburg
      virus (MARV) by aerosol to examine disease course and lethality. Macaques became
      febrile 4 to 7 days postexposure; the peak febrile response was delayed 1 to 2
      days in animals that received a lower dose; viremia coincided with the onset of
      fever. All 6 macaques succumbed to the infection, with the 3 macaques in the low
      dose group becoming moribund on day 9, a day later than the macaques in the high
      dose group. Gross pathologic lesions included maculopapular cutaneous rash;
      pulmonary congestion and edema; pericardial effusion; enlarged, congested, and/or
      hemorrhagic lymphoid tissues; enlarged friable fatty liver; and pyloric and
      duodenal congestion and/or hemorrhage. Fibrinous interstitial pneumonia was the
      most consistent pulmonary change. Lymphocytolysis and lymphoid depletion, as
      confirmed by TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate nick end labeling), were observed in the mediastinal lymph nodes and
      spleen. MARV antigen was detected in the lungs, mediastinal lymph nodes, spleen,
      and liver of all animals examined. In infected macaques, nuclear expression of
      interleukin-33 was lost in pulmonary arteriolar and mediastinal lymph node high
      endothelial venule endothelial cells; interleukin-33-positive fibroblastic
      reticular cells in the mediastinal lymph node were consistently negative for MARV
      antigen. These macaques exhibited a number of features similar to those of human
      filovirus infections; as such, this model of aerosolized MARV-Angola might be
      useful in developing medical countermeasures under the Animal Rule.

PMID- 20807826
TI  - "Elements of good training" editorial comment.

PMID- 20807828
TI  - Teratoid features in mixed hepatoblastoma.

PMID- 20807827
TI  - Elements of good training in anatomic pathology.

PMID- 20807830
TI  - Community management of anti-malarials in Africa and iatrogenic risk.
AB  - Distribution of anti-malarials at the community level is one of the interventions
      recommended to reduce mortality from febrile illnesses. Inappropriate treatment
      of fever with anti-malarials may result in missed diagnosis and delays in
      appropriate treatments including consideration of other illnesses than malaria.
      We report the case of an 8-year-old black girl receiving prophylaxis with
      sulfadoxine-pyrimethamine from the caretaker of the community during her holidays
      in Ivory Coast. A persistent fever suspected to be due to malaria was treated
      inappropriately with atovaquone-proguanil and then with sulfadoxine-pyrimethamine
      again. Cumulative toxicity of anti-malarials leads to irreversible hepatic
      damages requiring hepatic transplantation. Community caretakers must be aware of
      the potential side effects and the contraindications of anti-malarials. Early
      identification of drug-induced toxicity and immediate discontinuation of the drug
      are the more effective tools to limit the progression of tissue damage.

PMID- 20807831
TI  - Selenium and bladder cancer risk: a meta-analysis.
AB  - BACKGROUND: Selenium is considered to be an antioxidant, and its high levels have
      been inversely associated with cancer risk of several sites. This meta-analysis
      examined the relationship between levels of selenium measured in serum and
      toenails, and the risk of bladder cancer. METHODS: A meta-analysis using data
      from seven published epidemiologic studies (three case-control, three nested case
      control, one case-cohort) published before March 2010 was done to examine the
      association between levels of selenium and bladder cancer. Fixed and random
      effects analyses were done to calculate meta-odds ratio (mOR) and 95% confidence
      intervals (CI). Heterogeneity among studies was measured by the I(2) statistic.
      RESULTS: Overall, the risk of bladder cancer was inversely associated with
      elevated levels of selenium according to a random-effects model (mOR = 0.61; 95%
      CI, 0.42-0.87). The mORs were 0.95 (95% CI, 0.69-1.27) and 0.55 (95% CI, 0.32
      0.95) among men and women, respectively. Sex, type of sample specimen, smoking
      status, and study design were found to be potential sources of heterogeneity.
      CONCLUSIONS: A significant protective effect of selenium, observed mainly among
      women, may result from gender-specific differences in its accumulation and
      excretion. The heterogeneity found among studies was mainly linked to the
      different biological sample specimens used to measure the selenium concentrations
      and the small size of the studies. Although these results suggest a protective
      effect of selenium for bladder cancer risk, additional large studies are
      warranted to support these preliminary evidence. IMPACT: The present results
      suggest a beneficial effect of high selenium intake for bladder cancer risk.

PMID- 20807833
TI  - Frontmatter.

PMID- 20807832
TI  - Variety in fruit and vegetable consumption and the risk of lung cancer in the
      European prospective investigation into cancer and nutrition.
AB  - BACKGROUND: We investigated whether a varied consumption of vegetables and fruits
      is associated with lower lung cancer risk in the European Prospective
      Investigation into Cancer and Nutrition study. METHODS: After a mean follow-up of
      8.7 years, 1,613 of 452,187 participants with complete information were diagnosed
      with lung cancer. Diet diversity scores (DDS) were used to quantify the variety
      in fruit and vegetable consumption. Multivariable proportional hazards models
      were used to assess the associations between DDS and lung cancer risk. All models
      were adjusted for smoking behavior and the total consumption of fruit and
      vegetables. RESULTS: With increasing variety in vegetable subgroups, risk of lung
      cancer decreases [hazard ratios (HR), 0.77; 95% confidence interval (CI), 0.64
      0.94 highest versus lowest quartile; P trend = 0.02]. This inverse association is
      restricted to current smokers (HR, 0.73; 95% CI, 0.57-0.93 highest versus lowest
      quartile; P trend = 0.03). In continuous analyses, in current smokers, lower
      risks were observed for squamous cell carcinomas with more variety in fruit and
      vegetable products combined (HR/two products, 0.88; 95% CI, 0.82-0.95), vegetable
      subgroups (HR/subgroup, 0.88; 95% CI, 0.79-0.97), vegetable products (HR/two
      products, 0.87; 95% CI, 0.79-0.96), and fruit products (HR/two products, 0.84;
      95% CI, 0.72-0.97). CONCLUSION: Variety in vegetable consumption was inversely
      associated with lung cancer risk among current smokers. Risk of squamous cell
      carcinomas was reduced with increasing variety in fruit and/or vegetable
      consumption, which was mainly driven by the effect in current smokers. IMPACT:
      Independent from quantity of consumption, variety in fruit and vegetable
      consumption may decrease lung cancer risk.

PMID- 20807835
TI  - Specialized compartments of cardiac nuclei exhibit distinct proteomic anatomy.
AB  - As host to the genome, the nucleus plays a critical role as modulator of cellular
      phenotype. To understand the totality of proteins that regulate this organelle,
      we used proteomics to characterize the components of the cardiac nucleus.
      Following purification, cardiac nuclei were fractionated into biologically
      relevant fractions including acid-soluble proteins, chromatin-bound molecules and
      nucleoplasmic proteins. These distinct subproteomes were characterized by liquid
      chromatography-tandem MS. We report a cardiac nuclear proteome of 1048 proteins-
      only 146 of which are shared between the distinct subcompartments of this
      organelle. Analysis of genomic loci encoding these molecules gives insights into
      local hotspots for nuclear protein regulation. High mass accuracy and
      complementary analytical techniques allowed the discrimination of distinct
      protein isoforms, including 54 total histone variants, 17 of which were
      distinguished by unique peptide sequences and four of which have never been
      detected at the protein level. These studies are the first unbiased analysis of
      cardiac nuclear subcompartments and provide a foundation for exploration of this
      organelle's proteomes during disease.

PMID- 20807837
TI  - A sample storage management system for biobanks.
AB  - SUMMARY: Establishment of large-scale biobanks of human specimens is essential to
      conduct molecular pathological or epidemiological studies. This requires
      automation of procedures for specimen cataloguing and tracking through complex
      analytical processes. The International Agency for Research on Cancer (IARC)
      develops a large portfolio of studies broadly aimed at cancer prevention and
      including cohort, case-control and case-only studies in various parts of the
      world. This diversity of study designs, structure, annotations and specimen
      collections is extremely difficult to accommodate into a single sample management
      system (SMS). Current commercial or academic SMS are often restricted to a few
      sample types and tailored to a limited number of analytic workflows [Voegele et
      al. (2007) A laboratory information management system (LIMS) for a high
      throughput genetic platform aimed at candidate gene mutation screening.
      Bioinformatics, 23, 2504-2506]. Thus, we developed a system based on a three-tier
      architecture and relying on an Oracle database and an Oracle Forms web
      application. Data are imported through forms or csv files, and information
      retrieval is enabled via multi-criteria queries that can generate different types
      of reports including tables, Excel files, trees, pictures and graphs. The system
      is easy to install, flexible, expandable and implemented with a high degree of
      data security and confidentiality. Both the database and the interface have been
      modeled to be compatible with and adaptable to almost all types of biobanks.
      AVAILABILITY AND IMPLEMENTATION: The SMS source codes, which are under the GNU
      General Public License, and supplementary data are freely available at
      'http://www-gcs.iarc.fr/sms.php' SUPPLEMENTARY INFORMATION: Supplementary data
      are available at Bioinformatics online.

PMID- 20807836
TI  - A robust method for quantitative high-throughput analysis of proteomes by 18O
      labeling.
AB  - MS-based quantitative proteomics plays an increasingly important role in
      biological and medical research and the development of these techniques remains
      one of the most important challenges in mass spectrometry. Numerous stable
      isotope labeling approaches have been proposed. However, and particularly in the
      case of (18)O-labeling, a standard protocol of general applicability is still
      lacking, and statistical issues associated to these methods remain to be
      investigated. In this work we present an improved high-throughput quantitative
      proteomics method based on whole proteome concentration by SDS-PAGE, optimized in
      gel digestion, peptide (18)O-labeling, and separation by off-gel isoelectric
      focusing followed by liquid chromatography-LIT-MS. We demonstrate that the off
      gel technique is fully compatible with (18)O peptide labeling in any pH range. A
      recently developed statistical model indicated that partial digestions and
      methionine oxidation do not alter protein quantification and that variances at
      the scan, peptide, and protein levels are stable and reproducible in a variety of
      proteomes of different origin. We have also analyzed the dynamic range of
      quantification and demonstrated the practical utility of the method by detecting
      expression changes in a model of activation of Jurkat T-cells. Our protocol
      provides a general approach to perform quantitative proteomics by (18)O-labeling
      in high-throughput studies, with the added value that it has a validated
      statistical model for the null hypothesis. To the best of our knowledge, this is
      the first report where a general protocol for stable isotope labeling is tested
      in practice using a collection of samples and analyzed at this degree of
      statistical detail.

PMID- 20807838
TI  - Novel sequence-based method for identifying transcription factor binding sites in
      prokaryotic genomes.
AB  - MOTIVATION: Computational techniques for microbial genomic sequence analysis are
      becoming increasingly important. With next-generation sequencing technology and
      the human microbiome project underway, current sequencing capacity is
      significantly greater than the speed at which organisms of interest can be
      studied experimentally. Most related computational work has been focused on
      sequence assembly, gene annotation and metabolic network reconstruction. We have
      developed a method that will primarily use available sequence data in order to
      determine prokaryotic transcription factor (TF) binding specificities. RESULTS:
      Specificity determining residues (critical residues) were identified from crystal
      structures of DNA-protein complexes and TFs with the same critical residues were
      grouped into specificity classes. The putative binding regions for each class
      were defined as the set of promoters for each TF itself (autoregulatory) and the
      immediately upstream and downstream operons. MEME was used to find putative
      motifs within each separate class. Tests on the LacI and TetR TF families, using
      RegulonDB annotated sites, showed the sensitivity of prediction 86% and 80%,
      respectively. AVAILABILITY: http://ural.wustl.edu/~gsahota/HTHmotif/

PMID- 20807840
TI  - Body temperature as a mouse pharmacodynamic response to bombesin receptor subtype
      3 agonists and other potential obesity treatments.
AB  - Treatment of rodents with a bombesin receptor subtype-3 (BRS-3) agonist reduces
      food intake and increases fasting metabolic rate, causing weight loss with
      continued treatment. In small mammals, core body temperature (T(b)) is regulated
      in part by nutritional status, with a reduced T(b) during fasting. We report that
      fed Brs3 knockout mice have a lower T(b), which is discordant with their
      nutritional status. Treatment of wild-type mice with a BRS-3 agonist increased
      T(b), more so when the baseline T(b) was reduced such as by fasting or during the
      inactive phase of the light cycle. With repeated BRS-3 agonist dosing, the T(b)
      increase attenuated despite continued weight loss efficacy. The increase in T(b)
      was not prevented by inhibitors of prostaglandin E (PGE) production but was
      partially reduced by a beta-adrenergic blocker. These results demonstrate that
      BRS-3 has a role in body temperature regulation, presumably secondary to its
      effect on energy metabolism, including effects on sympathetic tone. By making use
      of this phenomenon, the reversal of the fasting T(b) reduction was developed into
      a sensitive single-dose pharmacodynamic assay for BRS-3 agonism and other
      antiobesity compounds acting by various mechanisms, including sibutramine,
      cannabinoid-1, and melanin-concentrating hormone-1 receptor blockers, and
      melanocortin, beta3-adrenergic, and cholecystokinin-1 receptor agonists. These
      drugs increased both the fasted T(b) and the fasted, resting metabolic rates. The
      T(b) assay is a robust, information-rich assay that is simpler and has a greater
      throughput than measuring metabolic rate and is a practical, effective tool for
      drug discovery.

PMID- 20807839
TI  - A high-fat, ketogenic diet causes hepatic insulin resistance in mice, despite
      increasing energy expenditure and preventing weight gain.
AB  - Low-carbohydrate, high-fat ketogenic diets (KD) have been suggested to be more
      effective in promoting weight loss than conventional caloric restriction, whereas
      their effect on hepatic glucose and lipid metabolism and the mechanisms by which
      they may promote weight loss remain controversial. The aim of this study was to
      explore the role of KD on liver and muscle insulin sensitivity, hepatic lipid
      metabolism, energy expenditure, and food intake. Using hyperinsulinemic
      euglycemic clamps, we studied insulin action in mice fed a KD or regular chow
      (RC). Body composition was assessed by 1H magnetic resonance spectroscopy.
      Despite being 15% lighter (P < 0.001) than RC-fed mice because of a 17% increase
      in energy expenditure (P < 0.001), KD-fed mice manifested severe hepatic insulin
      resistance, as reflected by decreased suppression (0% vs. 100% in RC-fed mice, P
      < 0.01) of endogenous glucose production during the clamp. Hepatic insulin
      resistance could be attributed to a 350% increase in hepatic diacylglycerol
      content (P < 0.001), resulting in increased activation of PKCepsilon (P < 0.05)
      and decreased insulin receptor substrate-2 tyrosine phosphorylation (P < 0.01).
      Food intake was 56% (P < 0.001) lower in KD-fed mice, despite similar caloric
      intake, and could partly be attributed to a more than threefold increase (P <
      0.05) in plasma N-acylphosphatidylethanolamine concentrations. In conclusion,
      despite preventing weight gain in mice, KD induces hepatic insulin resistance
      secondary to increased hepatic diacylglycerol content. Given the key role of
      nonalcoholic fatty liver disease in the development of type 2 diabetes and the
      widespread use of KD for the treatment of obesity, these results may have
      potentially important clinical implications.

PMID- 20807842
TI  - Defective female reproductive function in 1,25(OH)2D-deficient mice results from
      indirect effect mediated by extracellular calcium and/or phosphorus.
AB  - We used mice with targeted deletion of 25-hydroxyvitamin D 1alpha-hydroxylase
      [1alpha(OH)ase(-/-)] to investigate the effects of calcium and phosphorus on
      defects in the reproductive system of 1,25-dihydroxyvitamin D [1,25(OH)(2)D]
      deficient female mice. The 1alpha(OH)ase(-/-) mice and their wild-type
      littermates were fed either a normal diet or a rescue diet (high calcium,
      phosphate, and lactose) starting from weaning until 3 mo of age. We then
      determined serum calcium and phosphorus levels, assessed gonadotropin and gonadal
      hormone production, and evaluated folliculogenesis, corpus luteum formation,
      ovarian angiogenesis, uterus development, and fertility. Results showed that
      hypocalcemic and hypophosphatemic female 1alpha(OH)ase(-/-) mice developed
      infertility accompanied by decreased estrogen and progestogen levels, elevated
      follicle-stimulating hormone and luteinizing hormone levels, defects in
      follicular development and corpus luteum formation, uterine hypoplasia, and
      decreased ovarian expression of angiogenic factors including vascular endothelial
      growth factor (VEGF), angiopoietin-1 and -2, and Tie-2. When serum calcium and
      phosphorus were normalized by the rescue diet, the defective reproductive
      phenotype in the female 1alpha(OH)ase(-/-) mice, including the dysfunction in the
      hypothalamic-pituitary-ovarian axis, and ovarian angiogenesis were reversed.
      These results indicate that the infertility seen in 1,25(OH)(2)D-deficient mice
      is not a direct effect of active vitamin D deficiency on the reproductive system
      but is an indirect effect mediated by extracellular calcium and phosphorus.

PMID- 20807841
TI  - Rostroventrolateral medullary neurons modulate glucose homeostasis in the rat.
AB  - Several lines of evidence support the view that the premotor sympathetic input to
      the adrenal gland arises from the rostroventrolateral medulla (RVLM). The aim of
      this study was to determine whether RVLM neurons play a role in glucose
      homeostasis. We identified RVLM neurons that control epinephrine secretion by
      searching for medullospinal neurons that responded to neuroglucoprivation induced
      by systemic 2-deoxyglucose (2-DG) administration. We tested the effect of
      disinhibition of the RVLM on arterial blood pressure and plasma glucose
      concentration. RVLM medullospinal barosensitive neurons (n = 17) were either
      unaffected or slightly inhibited by 2-DG. In contrast, we found a group (n = 6)
      of spinally projecting neurons that were excited by 2-DG administration. These
      neurons were not barosensitive and had spinal conduction velocities in the
      unmyelinated range (<1 m/s). These neurons may mediate epinephrine secretion and
      participate in the counterregulatory responses to neuroglucoprivation. To test
      the hypothesis that activation of the RVLM leads to adrenomedullary activation
      and subsequent hyperglycemia, we applied the GABA(A) antagonist bicuculline to
      the RVLM and measured blood pressure, heart rate, and blood glucose in rats with
      intact adrenals or after bilateral adrenalectomy. Disinhibition of the RVLM
      resulted in hypertension, tachycardia, and hyperglycemia (4.9 +/- 0.3 to 14.7 +/-
      0.9 mM, n = 5, P < 0.05). Adrenalectomy significantly reduced the hyperglycemic
      response but did not alter the cardiovascular responses. These data suggest that
      the RVLM is a key component of the neurocircuitry that is recruited in the
      counterregulatory response to hypoglycemia.

PMID- 20807843
TI  - Impact of pain question modifiers on spine augmentation outcome.
AB  - PURPOSE: To determine whether the reported pain severity changed significantly on
      the basis of specific types of pain questions posed to patients with spine
      augmentation. MATERIALS AND METHODS: Institutional review board approval and
      patient consent were obtained for this HIPAA-compliant, prospective study.
      Patients presenting for consideration of spine augmentation between November 2008
      and May 2009 were enrolled. Twenty-four patients were asked at initial
      presentation and at 30 days to grade their severity of back pain on a 10-point
      numeric rating scale in response to nine pain questions modified by the relative
      severity (most vs least severe), by activity (at rest vs with activity), and over
      time (previous day vs previous week). Statistical analysis included paired t
      tests to detect any differences in responses to the questions at both time
      points. RESULTS: Of the 24 patients, 15 (63%) underwent spine augmentation. For
      patients undergoing spine augmentation, baseline mean numeric rating score for
      "worst pain with activity over the past week" was 8.9 +/- 1.5 (standard
      deviation), compared with 2.9 +/- 2.7 for "least pain at rest over the past day"
      (P = .001). Interval change between baseline and 30-day assessments was
      relatively small for all nine questions (mean, 1.6; range, 0.2-2.2); the mean
      difference for eight of the nine questions did not reach statistical
      significance. The modifiers worst versus least and with activity versus at rest
      had a significant impact on the reported severity, while previous week versus
      previous day had minimal impact. CONCLUSION: Wide variation in the reported pain
      can be achieved simply by modifying specific pain questions to patients with
      spine augmentation.

PMID- 20807844
TI  - Measurement of thoracic bone mineral density with quantitative CT.
AB  - PURPOSE: To create standard thoracic bone mineral density (BMD) values for
      patients undergoing cardiac computed tomography (CT) by using thoracic
      quantitative CT and to compare these BMDs (in a subpopulation) with those
      obtained by using lumbar spine quantitative CT. MATERIALS AND METHODS: The
      institutional review board approved this HIPAA-compliant study. A total of 9585
      asymptomatic subjects (mean age, 56 years; age range, 30-90 years) who underwent
      coronary artery calcium scanning, including 4131 women, were examined. Patients
      with vertebral deformities or fractures were excluded. Six hundred forty-four
      subjects (322 of whom were female) also underwent lumbar quantitative CT. The
      mean thoracic vertebral BMDs for both sexes were reported separately in a
      subgroup of subjects aged 30 years and in 29 age-based subgroups in 2-year
      intervals from ages 30 to 90 years. The formulas used to calculate the female T
      score (T(f)) and the male T score (T(m)) on the basis of thoracic quantitative CT
      measurements were as follows: T(f) = (BMD(im) - 222)/36, and T(m) = (BMD(im) -
      215)/33, where BMD(im) is the individual mean BMD. Comparisons between thoracic
      quantitative CT and lumbar quantitative CT measurements, as well as analyses of
      intraobserver, interobserver, and interscan variability, were performed. RESULTS:
      The young-subgroup mean BMD was 221.9 mg/mL +/- 36.2 (standard deviation) for the
      female subjects and 215.2 mg/mL +/- 33.2 for the male subjects. The mean thoracic
      BMDs for the female and male subjects were found to be 20.7% higher and 17.0%
      higher, respectively, than the values measured with lumbar quantitative CT (P <
      .001 for both comparisons). A significant positive association between the
      thoracic and lumbar quantitative CT measurements (r > 0.85, P < .001) was found.
      Intraobserver, interobserver, and interscan variabilities in thoracic
      quantitative CT measurements were 2.5%, 2.6%, and 2.8%, respectively. CONCLUSION:
      There was a significant association between the mean thoracic and lumbar BMDs.
      Therefore, standard derived measurements (young-subgroup BMD +/- standard
      deviation) based on these data can be used with thoracic CT images to estimate
      the bone mineral status.

PMID- 20807845
TI  - Radiation dose to the conceptus from multidetector CT during early gestation: a
      method that allows for variations in maternal body size and conceptus position.
AB  - PURPOSE: To develop a method for estimating the radiation dose to the conceptus
      from multidetector computed tomography (CT) of the abdomen and pelvis in pregnant
      patients during the first 7 weeks of gestation. MATERIALS AND METHODS: This study
      was approved by the institutional review board and informed consent was obtained.
      A CT simulation software package was used to (a) develop voxelized models on the
      basis of image data from 117 nonpregnant patients who underwent abdominal and
      pelvic multidetector CT and (b) calculate dose at a position of the uterus
      assumed to be the position of the conceptus in case of pregnancy during the first
      7 weeks of gestation. Regression analysis was carried out to establish the
      relationship among conceptus dose, patient body size, and distance from the
      conceptus to the anterior skin surface. RESULTS: Normalized conceptus doses
      calculated by using the software package ranged from 0.335 to 0.785 mGy per
      absorbed dose to air. Conceptus dose showed a significant correlation with
      maternal body size and conceptus depth (R2 = 0.793, P < .001). A multivariable
      correlation of conceptus dose normalized to the free-in-air CT dose index
      (CTDI(F)) with conceptus depth and patient perimeter was produced for estimating
      conceptus dose from abdominal and pelvic multidetector CT. Conceptus dose data
      provided for a specific scanner can be applied to other scanners by using
      correction factors based on ratios between the weighted CT dose index and
      CTDI(F), resulting in inaccuracies in the estimation of conceptus dose of less
      than 12%. CONCLUSION: The radiation dose to the conceptus from abdominal and
      pelvic multidetector CT can be estimated with a method that allows for variations
      in maternal body size and conceptus position.

PMID- 20807846
TI  - Determination of renal stone composition with dual-energy CT: in vivo analysis
      and comparison with x-ray diffraction.
AB  - PURPOSE: To preoperatively assess the composition of urinary stones by using dual
      energy computed tomography (CT), with postoperative in vitro x-ray diffraction
      analysis as the reference standard. MATERIALS AND METHODS: Institutional review
      board approval was obtained, and all participants provided written informed
      consent. Twenty-seven patients aged 50-64 years with renal stones, who were
      scheduled for stone extraction with percutaneous nephrolithotomy (PCNL),
      preoperatively underwent nonenhanced single-source dual-energy multidetector CT
      with 2-mm section thickness, 1-mm increments, 140 kVp, and 250 mAs. Regions of
      interest were drawn on low- and high-energy images, and low- and high-energy
      attenuation ratios were calculated for each stone scanned in vivo. The
      attenuation ratios for the patients were compared with those for an in vitro
      stone library phantom model of 37 stones with known chemical compositions. After
      surgery, the extracted stones were analyzed by using x-ray diffraction. The
      results of in vivo multidetector CT and ex vivo chemical analysis were compared.
      RESULTS: Dual-energy low- and high-energy attenuation ratios measured with the
      phantom were less than 1.1 for uric acid, 1.1-1.24 for cystine, and greater than
      1.24 for calcified stones. Struvite stones had attenuation ratios that overlapped
      with calcified stone ratios and thus could not be assessed reliably. Four
      patients had mixed stones (<75% of a single component), and one patient had a
      struvite stone. Of 27 patients, 22 (82%) (exact confidence interval [CI]: 68%,
      92%) received a correct diagnosis with dual-energy CT: all six (100%; exact CI:
      54%, 100%) patients with uric acid stones, 15 (79%; exact CI: 62%, 95%) of the 19
      patients with calcium stones, and the one (100%) patient with a cystine stone.
      The patient with a struvite stone did not receive a correct dual-energy CT-based
      diagnosis. CONCLUSION: Dual-energy multidetector CT may enable accurate in vivo
      characterization of kidney stone composition.

PMID- 20807847
TI  - Urinary calculi composed of uric acid, cystine, and mineral salts:
      differentiation with dual-energy CT at a radiation dose comparable to that of
      intravenous pyelography.
AB  - PURPOSE: To retrospectively evaluate radiation dose, image quality, and the
      ability to differentiate urinary calculi of differing compositions by using low
      dose dual-energy computed tomography (CT). MATERIALS AND METHODS: The
      institutional review board approved this retrospective study; informed consent
      was waived. A low-dose dual-energy CT protocol (tube voltage and reference
      effective tube current-time product, 140 kV and 23 mAs and 80 kV and 105 mAs;
      collimation, 64 * 0.6 mm; pitch, 0.7) for the detection of urinary calculi was
      implemented into routine clinical care. All patients (n = 112) who were examined
      with this protocol from July 2008 to August 2009 were included. The composition
      of urinary calculi was assessed by using commercially available postprocessing
      software and was compared with results of the reference standard (ex vivo
      infrared spectroscopy) in 40 patients for whom the reference standard was
      available. Effective doses were calculated. Image quality was rated subjectively
      and objectively and was correlated with patient size expressed as body cross
      sectional area at the level of acquisition by using Spearman correlation
      coefficients. RESULTS: One calcified concrement in the distal ureter of an obese
      patient was mistakenly interpreted as mixed calcified and uric acid. One struvite
      calculus was falsely interpreted as cystine. All other uric acid, cystine, and
      calcium-containing calculi were correctly identified by using dual-energy CT. The
      mean radiation dose was 2.7 mSv. The average image quality was rated as
      acceptable, with a decrease in image quality in larger patients. CONCLUSION: Low
      dose unenhanced dual-source dual-energy CT can help differentiate between
      calcified, uric acid, and cystine calculi at a radiation dose comparable to that
      of conventional intravenous pyelography. Because of decreased image quality in
      obese patients, only nonobese patients should be examined with this protocol.

PMID- 20807848
TI  - Metacarpophalangeal joints in rheumatoid arthritis: delayed gadolinium-enhanced
      MR imaging of cartilage--a feasibility study.
AB  - PURPOSE: To evaluate the feasibility of delayed gadolinium-enhanced magnetic
      resonance (MR) imaging of the cartilage of metacarpophalangeal (MCP) joints in
      patients with rheumatoid arthritis (RA) compared with that in control subjects.
      MATERIALS AND METHODS: Institutional review board approval and informed consent
      were obtained. Thirty-one MCP joints in 10 patients with RA (mean age, 59 years;
      range, 35-77 years) and six healthy volunteers (mean age, 51 years; range, 30-71
      years) were examined with delayed gadolinium-enhanced MR imaging of cartilage.
      Sagittal images of the second and third MCP joints (hereafter, MCP II and MCP
      III) were acquired with a three-dimensional dual-flip-angle gradient-echo
      sequence at 3.0 T. B(1) field inhomogeneity-corrected T1 maps were calculated,
      and delayed gadolinium-enhanced MR imaging of cartilage values for phalangeal and
      metacarpal cartilage were determined. In addition, cartilage thickness was
      measured. A nonparametric Mann-Whitney U test was used to assess differences
      between groups. RESULTS: Phalangeal and metacarpal delayed gadolinium-enhanced MR
      imaging of cartilage values in patients with RA (MCP II: 388 msec +/- 105
      [standard deviation] and 342 msec +/- 79, respectively; MCP III: 409 msec +/- 96
      and 371 msec +/- 89, respectively) were significantly lower than in control
      subjects (MCP II: 598 msec +/- 62 and 560 msec +/- 51, respectively; MCP III: 586
      msec +/- 57 and 561 msec +/- 80, respectively). Cartilage thickness of both
      joints was comparable in patients with RA (MCP II: 1.28 mm +/- 0.50, MCP III:
      1.17 mm +/- 0.24) and control subjects (MCP II: 1.42 mm +/- 0.33, MCP III: 1.18
      mm +/- 0.26). CONCLUSION: Delayed gadolinium-enhanced MR imaging of cartilage of
      the MCP joints is feasible at 3.0 T. Delayed gadolinium-enhanced MR imaging of
      cartilage may help to assess cartilage degeneration in morphologically normal
      appearing MCP II and III cartilage in patients with RA.

PMID- 20807849
TI  - Can preoperative axillary US help exclude N2 and N3 metastatic breast cancer?
AB  - PURPOSE: To determine the false-negative rate of axillary ultrasonography (US)
      with respect to stage N2 and N3 metastatic disease in patients with newly
      diagnosed breast cancer. MATERIALS AND METHODS: The study was approved by the
      institutional review board and complied with the HIPAA; the requirement for
      informed consent was waived. A retrospective search of radiology records
      identified 435 consecutive patients with breast cancer aged 25-88 years who
      underwent preoperative axillary US from January 1, 2006, to December 31, 2007.
      Two hundred five patients (203 women and two men) had 208 negative US scans with
      correlative surgical and/or pathologic lymph node data. Criteria used to detect
      abnormal lymph nodes included subjective assessment of diffuse cortical
      thickening, focal cortical mass/thickening, and replacement or effacement of the
      fatty hilum. Tumor type, grade, size, and hormone receptor status were
      documented. Statistical analysis was performed with the Fisher exact test.
      RESULTS: Of the 208 axillae with negative findings at US, 14 (6.7%) had a final
      node stage of N2 or N3. Twelve of the 208 axillae (5.8%) had stage N2 disease and
      two (1.0%) had stage N3 disease. Of the 14 axillae with stage N2 or N3 disease,
      eight (57.1%) had lobular histologic characteristics and six (42.9%) had ductal
      histologic characteristics. The false-negative rate for N2 and N3 disease was
      4.1% (six of 146 axillae) for invasive ductal cancer and 17% (eight of 47
      axillae) for invasive lobular cancer (P < .01). None of the 14 axillae with stage
      N2 or N3 disease were "triple negative" (ie, estrogen receptor negative,
      progesterone receptor negative, and human epidermal growth factor receptor type 2
      negative). CONCLUSION: Preoperative axillary US excluded 96% of N2 and N3
      invasive ductal metastases. The false-negative rate for N2 and N3 invasive
      lobular cancer was significantly higher than that for invasive ductal cancer,
      which suggests that axillary US cannot be used to exclude N2 and N3 metastases in
      these patients.

PMID- 20807850
TI  - Atrial and ventricular functional and structural adaptations of the heart in
      elite triathletes assessed with cardiac MR imaging.
AB  - PURPOSE: To assess cardiac morphologic and functional adaptations in elite
      triathletes with magnetic resonance (MR) imaging and to compare findings to those
      in recreationally active control subjects. MATERIALS AND METHODS: The
      institutional review board approved the study, and written informed consent was
      obtained from all subjects. Twenty-six male triathletes (mean age +/- standard
      deviation, 27.9 years +/- 3.5; age range, 18-35 years) and 27 nonathletic male
      control subjects (mean age, 27.3 years +/- 3.7; age range, 20-34 years) underwent
      cardiac MR imaging. Electrocardiographically gated steady-state free-precession
      cine MR imaging was used to measure indexed left ventricular (LV) and right
      ventricular (RV) myocardial mass, end-diastolic and end-systolic volumes, stroke
      volume, ejection fraction (EF), and cardiac index at rest. The ventricular
      remodeling index, which is indicative of the pattern of cardiac hypertrophy, was
      calculated. The maximum left atrial (LA) volume was calculated according to the
      biplane area-length method. Differences between means of athletes and control
      subjects were assessed by using the Student t test for independent samples.
      RESULTS: The atrial and ventricular volume and mass indexes in triathletes were
      significantly greater than those in control subjects (P < .001). In 25 of the 26
      athletes, the LV and RV end-diastolic volumes were greater than the normal ranges
      reported in the literature for healthy, male, nonathletic control subjects (47-92
      mL/m(2) and 55-105 mL/m(2), respectively). There was a strong positive
      correlation between end-diastolic volume and myocardial mass (P < .01). The mean
      LV and RV remodeling indexes of the athletes (0.73 g/mL +/- 0.1 and 0.22 g/mL +/-
      0.01, respectively) were similar to those of the control subjects (0.71 g/mL +/-
      0.1 [P = .290] and 0.22 g/mL +/- 0.01 [P = .614], respectively). There was a
      negative correlation between LA end-systolic volume and heart rate (P < .01).
      CONCLUSION: Changes in cardiac morphologic characteristics and function in elite
      triathletes, as measured with cardiac MR imaging, reflect a combination of
      eccentric and concentric remodeling with regulative enlargement of atrial and
      ventricular chambers. These findings are different from what has been observed in
      previous studies in other types of elite athletes.

PMID- 20807851
TI  - Computer-aided detection of lung cancer on chest radiographs: effect on observer
      performance.
AB  - PURPOSE: To assess how computer-aided detection (CAD) affects reader performance
      in detecting early lung cancer on chest radiographs. MATERIALS AND METHODS: In
      this ethics committee-approved study, 46 individuals with 49 computed
      tomographically (CT)-detected and histologically proved lung cancers and 65
      patients without nodules at CT were retrospectively included. All subjects
      participated in a lung cancer screening trial. Chest radiographs were obtained
      within 2 months after screening CT. Four radiology residents and two experienced
      radiologists were asked to identify and localize potential cancers on the chest
      radiographs, first without and subsequently with the use of CAD software. A
      figure of merit was calculated by using free-response receiver operating
      characteristic analysis. RESULTS: Tumor diameter ranged from 5.1 to 50.7 mm
      (median, 11.8 mm). Fifty-one percent (22 of 49) of lesions were subtle and
      detected by two or fewer readers. Stand-alone CAD sensitivity was 61%, with an
      average of 2.4 false-positive annotations per chest radiograph. Average
      sensitivity was 63% for radiologists at 0.23 false-positive annotations per chest
      radiograph and 49% for residents at 0.45 false-positive annotations per chest
      radiograph. Figure of merit did not change significantly for any of the observers
      after using CAD. CAD marked between five and 16 cancers that were initially
      missed by the readers. These correctly CAD-depicted lesions were rejected by
      radiologists in 92% of cases and by residents in 77% of cases. CONCLUSION: The
      sensitivity of CAD in identifying lung cancers depicted with CT screening was
      similar to that of experienced radiologists. However, CAD did not improve cancer
      detection because, especially for subtle lesions, observers were unable to
      sufficiently differentiate true-positive from false-positive annotations.

PMID- 20807852
TI  - Global contrast in nuclear medicine.

PMID- 20807853
TI  - Ethical issues in radioisotope shortages: rationing and priority setting.
AB  - In recent years, shortages of radioisotopes that cannot be stockpiled have
      created a scenario in which they may be considered, periodically, a scarce
      medical resource. This discussion focuses on the just allocation of medical
      radioisotopes and presents the dominant ethical frameworks for rationing and
      priority setting in the patient populations most affected. Priority setting is
      necessary when demand for a scarce resource exceeds supply. On completion of this
      article, the reader will be able to describe the origins of rationing and
      priority setting in medicine, as well as ethically sound frameworks for
      rationing. Finally, the process for priority setting and the need for
      transparency of this process in the nuclear medicine setting are outlined.

PMID- 20807854
TI  - Impact of 18F-FDG PET/CT with retrograde filling of the urinary bladder in
      patients with suspected pelvic malignancies.
AB  - The purpose of this study was to assess the feasibility of selective pelvic
      PET/CT with retrograde bladder irrigation in evaluating pelvic pathologies.
      METHODS: Thirty-eight patients (22 women and 16 men), with a mean age of 61 y
      (range, 41-81 y) and a neoplastic background (most of them of pelvic pathology),
      were assessed with PET/CT. The most prevalent findings were urothelial (14
      cases), gynecologic (12 cases), and rectal (7 cases) cancers. All but 3 patients
      had undergone previous surgical procedures or radio- or chemotherapy. Twenty-two
      patients had suspected pelvic pathology on a previous diagnostic CT scan. All the
      patients underwent a standard PET/CT protocol (from head to upper thighs) 60 min
      after the intravenous injection of 370 MBq of (18)F-FDG. Additional delayed
      pelvic PET/CT images were acquired with a filled-bladder technique. Both series
      of images were assessed by 2 experienced observers. A lesion was classified as
      malignant if it showed a standardized uptake value greater than 2.5 or, in the
      case of subcentimetric lesions, any uptake greater than background activity that
      persisted or increased on delayed pelvic imaging. All lesions were evaluated
      histologically or by clinical follow-up. RESULTS: Twenty-seven of 43 studies were
      categorized as pathologic using PET/CT. Nineteen studies showed abnormalities in
      the pelvis; the findings of 5 of these studies were false-positive. Ten studies
      showed pathologic (18)F-FDG uptake in the bladder wall; in 7 of these studies the
      uptake was found to be true-positive on histopathologic examination. The
      sensitivity, specificity, positive predictive value, negative predictive value,
      and accuracy of PET/CT in the pelvic assessment were 100%, 83%, 74%, 100%, and
      76%, respectively. The retrograde filling reduced the interference with
      physiologic urinary accumulation of (18)F-FDG in patients with possible pelvic
      lesions; no false-negative results were documented. CONCLUSION: In (18)F-FDG PET
      studies, retrograde filling of the urinary bladder is recommended to assess
      bladder wall lesions and malignancies in other pelvic locations.

PMID- 20807855
TI  - Assessment of patient exposure to X-radiation from SPECT/CT scanners.
AB  - In the operation of any SPECT/CT system, in addition to internal radiation
      exposure (gamma-ray) resulting from administration of radiopharmaceuticals,
      external radiation exposure (x-ray) from the CT device has to be taken into
      consideration in the light of recommendations from the International Commission
      on Radiological Protection. These recommendations include justification of
      practices (the use of radiation produces sufficient benefit to offset any risks
      caused by the use of radiation), optimization (the incurred exposure by the use
      of radiation should be kept as low as reasonably achievable), and dose
      limitation. The internal radiation exposures of each organ after administration
      of radiopharmaceuticals are calculated by the MIRD Committee method. For example,
      the internal radiation exposure index for brain perfusion scintigraphy is 0.8
      mGy/37 MBq for N-isopropyl-4-iodoamphetamine((123)I) hydrochloride or 0.19 mGy/37
      MBq for ethyl cysteinate dimer. On the other hand, the external radiation
      exposure from a CT device is calculated using the CT dose index volume (CTDIvol)-
      a measured and calculated value unique to the CT scanner and scan parameters used
      -and a dose-length product, which is obtained from CT conditions and generally
      used as a reference value for CT radiation exposure. However, CTDIvol and dose
      length product are calculated values unique to each device, not the value of
      external radiation exposures of each organ. Therefore, we believe that it is
      necessary to measure the total (internal plus external) radiation exposure dose
      from CT. In the present study, using an anthropomorphic phantom for deep-body
      total absorbed dose measurement, we evaluated the radiation exposure doses (organ
      absorbed doses) of each organ under various CT conditions. METHODS: The radiation
      exposure doses of each organ were measured by inserting thermoluminescent
      dosimeter elements into the phantom under various CT conditions. RESULTS: The
      following were brain radiation exposure doses in the head region. For 90 kVp and
      25 mAs, 1.39 mGy (CTDIvol, 1.8 mGy), for 90 kVp and 300 mAs, 17.00 mGy (CTDIvol,
      21.2 mGy), for 120 kVp and 25 mAs, 3.21 mGy (CTDIvol, 3.8 mGy), for 120 kVp and
      300 mAs, 37.79 mGy (CTDIvol, 47.7 mGy), for 140 kVp and 25 mAs, 5.08 mGy
      (CTDIvol, 5.5 mGy), and for 140 kVp and 300 mAs, 65.07 mGy (CTDIvol, 65.6 mGy).
      The eye radiation exposure doses were as follows. For 90 kVp and 25 mAs, 1.94 mGy
      (CTDIvol, 1.8 mGy), for 90 kVp and 300 mAs, 20.31 mGy (CTDIvol, 21.2 mGy), for
      120 kVp and 25 mAs, 3.71 mGy (CTDIvol, 3.8 mGy), for 120 kVp and 300 mAs, 49.72
      mGy (CTDIvol, 47.7 mGy), for 140 kVp and 25 mAs, 5.44 mGy (CTDIvol, 5.5 mGy), and
      for 140 kVp and 300 mAs, 69.76 mGy (CTDIvol, 65.6 mGy). In addition, the
      radiation exposure doses of the cervical, thoracic, abdominal, and pelvic regions
      were measured in detail. CONCLUSION: Our estimated external radiation exposure
      doses (x-ray) of each organ under various CT conditions, along with the internal
      radiation exposure doses (gamma-ray) resulting from the administration of
      radiopharmaceuticals, seem to be useful as reference values in understanding the
      radiation exposure doses for performing various nuclear medicine examinations.

PMID- 20807856
TI  - Development of a comprehensive software application for calculations in nuclear
      medicine and radiopharmacy.
AB  - In the daily practice of in-hospital or centralized radiopharmacies, there is a
      need to perform reliable numeric calculations. Furthermore, several nuclear
      medicine diagnostic tests also involve carrying out calculations. In both cases,
      these calculations are sometimes complex or tedious and prone to error. We report
      the development of a computer software program that performs a comprehensive
      range of calculations required in radiopharmacy and nuclear medicine diagnostic
      tests. METHODS: This software was developed and compiled in the Visual Basic
      programming language using algorithms and methods reflected in the scientific
      literature. RESULTS: We developed 2 versions of the software program, which we
      call Nucleolab. It automatically performs calculations relating to radiopharmacy
      practice as well as 9 diagnostic nuclear medicine tests. The 0.1 version performs
      all these calculations, and the 1.2 version also has a database that enables the
      user to save and recover diagnostic test results and issue custom reports. The
      software can be downloaded at www.radiofarmacia.org/nucleolab-english.
      CONCLUSION: To our knowledge, ours is the first attempt to develop a
      comprehensive software application that facilitates calculations in nuclear
      medicine and radiopharmacy, reducing errors and improving efficiency and
      accuracy.

PMID- 20807857
TI  - The cross-effects of cigarette and betel nut consumption in Taiwan: have tax
      increases made a difference?
AB  - This paper empirically identifies cross-price elasticities of betel nut and
      cigarette consumption in Taiwan based on the Central Bureau of Statistics demand
      model. It compares reduction of cigarette consumption as a result of the proposed
      Betel Nut Health Tax with reduction of betel nut consumption as a result of the
      Tobacco Health and Welfare Taxes levied in 2002 and 2006, in order to determine
      which tax is most effective. Results from a simulated comparative analysis
      indicate that the Betel Nut Health Tax reduces cigarette consumption to a much
      greater extent than the Tobacco Health and Welfare Taxes reduce betel nut
      consumption.

PMID- 20807858
TI  - People use self-control to risk personal harm: an intra-interpersonal dilemma.
AB  - People will smoke cigarettes, drink alcohol, binge eat, drink coffee, eat chili
      peppers, fail tests, steal, ingest illicit drugs, engage in violent and sadistic
      actions including killing, have sex, and seek to become HIV positive for the sake
      of interpersonal acceptance. The self-control for personal harm model
      reconceptualizes behaviors that have both urge and control components as
      demonstrating either successful or failed self-control, depending on the
      incipient urge. The model underscores the role of expected social rewards as an
      important incentive for which people sometimes engage in personally risky and
      aversive behaviors despite feeling that they would rather avoid the behaviors and
      attendant harm. Research from diverse perspectives converges to show that risky
      behaviors, which might on the surface appear to be self-control failures, can in
      fact require self-control exertion.

PMID- 20807859
TI  - Electromyographic study of the popliteus muscle in the dynamic stabilization of
      the posterolateral corner structures of the knee.
AB  - BACKGROUND: The posterolateral corner of the knee consists of static and dynamic
      stabilizing structures. Knee injuries often include the posterolateral
      structures. The popliteus muscle-tendon unit is known as the major dynamic
      stabilizer of the posterolateral corner. HYPOTHESIS: The dynamic stabilization of
      the posterolateral structures of the knee via the popliteus muscle-tendon unit
      during a squatting exercise follows a constant activation pattern. STUDY DESIGN:
      Controlled laboratory study. METHODS: Within the pilot study, 6 volunteers
      performed 2 exercises to verify the electrode position scheme and to analyze
      cross-talk. In the main study 2 static exercises (standing and standing with
      knees flexed 90 degrees ) and 2 dynamic exercises (isolated popliteus muscle
      activation and squats) were recorded in 17 volunteers. Electromyograms were
      obtained of the popliteus, medial and lateral gastrocnemius, and quadriceps
      muscles. Knee angle-related muscle activity was recorded. RESULTS: In the pilot
      study it was assumed that the chosen electrode position allowed selective
      measurement of popliteus muscle activity. In the main study the mean popliteus
      onset angle was 43 degrees  +/- 14 degrees  of flexion; activity lasted through
      the reversal point of the squat to 58 degrees  +/- 21 degrees  of flexion during
      extension movement. Popliteus activity during all testing cycles revealed that
      the activity in the standing position is the smallest. The highest activity was
      recorded during the squat and the popliteus muscle-tendon unit exercise.
      CONCLUSION: This study demonstrates an activation pattern of the popliteus muscle
      tendon unit with high interindividual differences in the onset angles. A constant
      activation during the reversal phase of the squatting exercise could be observed.
      CLINICAL RELEVANCE: Reconstructive procedures of the posterolateral structures
      often include reconstruction of the popliteus muscle-tendon unit. Reconstructive
      procedures are usually done in a static manner, thus not addressing the dynamic
      stabilizing structure in a true functional way. The findings of the current study
      may be a useful contribution to the ongoing discussion of this topic.

PMID- 20807860
TI  - Passive ranges of motion of the hips and their relationship with pitching
      biomechanics and ball velocity in professional baseball pitchers.
AB  - BACKGROUND: Pelvis and trunk motions during baseball pitching are associated with
      ball velocity. Thus, limits in hip flexibility may adversely affect pitching
      biomechanics and the ability to generate ball velocity. HYPOTHESES: Professional
      baseball pitchers will have less passive range of motion in the nondominant hip
      and the measured ranges of motion of both the nondominant and dominant hips will
      correlate with biomechanical parameters of the lower extremity among professional
      pitchers. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS:
      Nineteen healthy professional baseball pitchers volunteered for testing. Fluid
      goniometry was used to measure passive range of motion of adduction (ADD),
      abduction (ABD), internal rotation, external rotation, total arc of rotation, and
      total arc of ADD + ABD. Pitching biomechanical data were collected using an
      automated 3-dimensional motion analysis system while participants threw
      fastballs. RESULTS: Pitchers possessed significantly less passive range of motion
      in the nondominant hip when compared with the dominant hip for all ranges. Total
      arc of rotation of the nondominant hip correlated with ball velocity (r = .50).
      Total arc of ADD + ABD in the nondominant hip and ABD in the nondominant hip were
      correlated with stride length (r = -.72 and .70, respectively). Dominant hip ABD
      (r = .63), total arc of rotation in the nondominant hip (r = -.45), and total arc
      of ADD + ABD of the dominant hip (r = .44) were correlated with trunk separation.
      Total arc of ADD + ABD of the nondominant hip (r = -.52) and total arc of
      rotation of the dominant hip (r = -.44) were correlated with pelvic orientation.
      CONCLUSION: Passive range of motion is smaller in the nondominant hip than the
      dominant hip among professional pitchers. The measured disparity between the hips
      is significantly correlated with various pitching biomechanical parameters of the
      trunk and pelvis. Future research is required to investigate a causal
      relationship between less hip passive range of motion and both ball velocity and
      pitching biomechanics.

PMID- 20807861
TI  - Restoration of knee volume using selected arthroscopic releases.
AB  - BACKGROUND: Inflammation and subsequent fibrosis, adhesions, or plicae may limit
      normal capsular compliance and decrease volume capacity of the knee. HYPOTHESIS:
      Patients with fibrosis, anterior interval scarring, adhesions, or palpable
      painful plicae will have decreased knee volumes when compared to controls, and
      selective arthroscopic releases will restore volume to normal levels. STUDY
      DESIGN: Descriptive laboratory study and cohort study; Level of evidence, 2.
      METHODS: In part I, knee volume and pressure were recorded in 14 fresh-frozen
      human cadaveric knees, and the maximum volume capacity was identified before
      capsular disruption. In part II, 49 patients undergoing arthroscopy were divided
      into 2 groups based on intraoperative volume assessment at 50 mm H(2)O pressure:
      group 1 (n = 20) with normal volume (<1 standard deviation below the mean
      established in part I) and group 2 (n = 29) knees with deficient volume (>1
      standard deviation below mean). Group 2 underwent volume-changing procedures such
      as lysis of adhesions, anterior interval release, and plica resections, while
      group 1 underwent volume-neutral procedures including meniscal or chondral
      surgery. The knee volume was then reassessed after arthroscopy. RESULTS: The
      average volume capacity of the knees in the cadaveric study was 87.5 +/- 21.7 mL
      (range, 50-120 mL). There was no statistical difference between the presurgical
      (98.9 +/- 29.8 mL) and postsurgical volumes (99.4 +/- 29.1 mL) in group 1; P =
      .65. The presurgical volume in group 2 (46.1 +/- 13.0 mL) was significantly lower
      than group 1 (P = .001). The group 2 volume increased to 78.5 +/- 24.2 mL after
      surgery (P = .001), with an average change in volume of 75.5%. The mean change in
      volume after surgery was significantly greater in group 2 (32.3 mL) versus group
      1 (0.45 mL) (P = .001). At 1-year follow-up, the mean Tegner score in the volume
      compromised group 2 increased from 2.0 +/- 1.4 preoperatively to 4.0 +/- 2.0
      postoperatively (P = .01), the Lysholm score increased from 45.0 +/- 24.0
      preoperatively to 76.8 +/- 25.4 postoperatively (P = .003), and the average Short
      Form-12 quality of life score increased from 32.4 +/- 8.7 preoperatively to 45.0
      +/- 11.0 postoperatively (P = .005). CONCLUSIONS: The average volume of the human
      knee in this study was between 65 and 110 mL (+/-1 standard deviation of mean of
      87.5 mL). Although patients with chronic knee pain may have pain from multiple
      sources, some may have diminished knee volume, and selected arthroscopic releases
      can restore knee volume to near-normal levels.

PMID- 20807862
TI  - MYB75 functions in regulation of secondary cell wall formation in the Arabidopsis
      inflorescence stem.
AB  - Deposition of lignified secondary cell walls in plants involves a major
      commitment of carbon skeletons in both the form of polysaccharides and
      phenylpropanoid constituents. This process is spatially and temporally regulated
      by transcription factors, including a number of MYB family transcription factors.
      MYB75, also called PRODUCTION OF ANTHOCYANIN PIGMENT1, is a known regulator of
      the anthocyanin branch of the phenylpropanoid pathway in Arabidopsis (Arabidopsis
      thaliana), but how this regulation might impact other aspects of carbon
      metabolism is unclear. We established that a loss-of-function mutation in MYB75
      (myb75-1) results in increased cell wall thickness in xylary and interfascicular
      fibers within the inflorescence stem. The total lignin content and S/G ratio of
      the lignin monomers were also affected. Transcript profiles from the myb75-1
      inflorescence stem revealed marked up-regulation in the expression of a suite of
      genes associated with lignin biosynthesis and cellulose deposition, as well as
      cell wall modifying proteins and genes involved in photosynthesis and carbon
      assimilation. These patterns suggest that MYB75 acts as a repressor of the lignin
      branch of the phenylpropanoid pathway. Since MYB75 physically interacts with
      another secondary cell wall regulator, the KNOX transcription factor KNAT7, these
      regulatory proteins may form functional complexes that contribute to the
      regulation of secondary cell wall deposition in the Arabidopsis inflorescence
      stem and that integrate the metabolic flux through the lignin, flavonoid, and
      polysaccharide pathways.

PMID- 20807863
TI  - Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS)
      defined morbidity and mortality associated with pediatric ventricular assist
      device support at a single US center: the Stanford experience.
AB  - BACKGROUND: The use of ventricular assist devices (VADs) to bridge pediatric
      patients to heart transplantation has increased dramatically over the last 15
      years. In this report, we present the largest US single-center report of
      pediatric VAD use to date. We present detailed descriptions of morbidity and
      mortality associated with VAD support, using standard Interagency Registry for
      Mechanically Assisted Circulatory Support (INTERMACS) criteria for pediatrics to
      facilitate the comparison of these results to other studies. METHODS AND RESULTS:
      We retrospectively identified 25 patients younger than 18 years with 27 episodes
      of mechanical circulatory support using VADs as bridge to heart transplantation
      from January 1998 to December 2007. Survival to transplant for the entire cohort
      was 74%. The most common major morbidities, as defined by INTERMACS criteria for
      a pediatric population, were respiratory failure, major localized infections,
      major bleeding events, hepatic dysfunction, and right heart failure. Major
      neurological events occurred in 48% of the study population. The median time to
      the first occurrence of an adverse event was less than 14 days for respiratory
      failure, right heart failure, major localized infection, and major bleeding.
      Patients who died before transplantation had significantly more adverse events
      per day of support than did those who were successfully transplanted. Episodes of
      major bleeding, tamponade, acute renal failure, respiratory failure, and right
      heart failure were all associated with increased risk of mortality. CONCLUSIONS:
      INTERMACS criteria can be successfully used to analyze pediatric VAD outcomes.
      These data serve as a baseline for future studies of VAD support in children and
      indicate good survival rates but considerable morbidity.

PMID- 20807864
TI  - Agnew's general strain theory reconsidered: a phenomenological perspective.
AB  - Since its inception, strain theory has attempted to explore the dynamic evoked
      between the process of goal identification and the process of goal acquisition as
      this relates to subsequent criminal behavior. Over the years of its development,
      strain theorists have attempted to broaden the initial scope of this perspective.
      Robert Agnew with his general strain theory has sought to introduce a variety of
      other factors relative to the experience of strain and the capacity they
      represent concerning subsequent criminal activity. However, these recent
      developments have not addressed until recently, and only in somewhat limited
      ways, the theoretical and methodologic implications and limits of this
      theoretical approach. This article proposes that the way in which Agnew's
      formulation of general strain, particularly in its most recent conceptualization
      as story lines, fundamentally transforms the theoretical and methodological
      grounding of this approach but fails to offer a clearly articulated alternative
      theoretical perspective by which to conceptualize this "turn." Phenomenology
      provides such an alternative perspective and helps to greatly expand our
      understanding of the human experience of strain.

PMID- 20807866
TI  - Development of cephradine-induced acquired factor V inhibitors: a case report.
AB  - OBJECTIVE: To report a case of cephalosporin-induced factor V inhibitor
      development, an uncommon but potentially fatal condition characterized by severe
      hemorrhage. CASE SUMMARY: A 71-year-old Chinese man presented with factor V
      inhibitors after a 7-day cephradine course for a urinary tract infection,
      characterized by abnormal prothrombin time (PT) and activated partial
      thromboplastin time (aPTT), gross hematuria, upper gastrointestinal bleeding, and
      left groin hematoma. Systemic corticosteroid administration restored his factor V
      activity levels, PT, and aPTT to within normal limits, and hemorrhagic symptoms
      resolved. Three weeks after successful treatment of bleeding diathesis, he
      received another 8-day cephradine course for cellulitis. After another 4 weeks,
      he suffered from recurrent factor V inhibitors presented with abnormal PT, aPTT,
      and upper gastrointestinal bleeding. The patient eventually died due to
      hemorrhagic shock despite a second course of corticosteroids. DISCUSSION:
      Cephalosporins are known to cause coagulopathy via hypoprothrombinemia. Another
      pathway seldom mentioned in the literature is factor V inhibitor induction, which
      may result in factor V deficiency. In our patient, factor V deficiency due to
      inhibitors developed each time that the patient received repeated cephradine
      treatment. According to the Naranjo probability scale, the relation between the
      formation of factor V inhibitors and cephradine treatment was probable.
      CONCLUSIONS: Because cephalosporins are commonly used for their wide therapeutic
      index and few adverse effects, iatrogenic complications associated with these
      drugs may be neglected or underdiagnosed. On the basis of our patient's report,
      careful review of medical records to avoid reexposure to the offending drug
      cannot be overemphasized.

PMID- 20807865
TI  - Florence Nightingale in absentia: nursing and the 1893 Columbian Exposition.
AB  - In 1893, Chicago hosted the Columbian Exposition. This event showcased America's
      social, cultural, and scientific advances and its growing cultural parity with
      Western Europe. This was the first major exposition in which women played a
      prominent role. Integral to the fair was a series of Congresses that provided an
      international platform for discussion of social issues. The Congress on
      Hospitals, Dispensaries, and Nursing, a section of the International Congress of
      Charities, Correction, and Philanthropy, particularly focused on health care
      issues. Nursing leaders from Europe and North America participated. Although
      Florence Nightingale provided a major paper that was read at the Congress, she
      was unable to attend the event. The intent of this article is to examine the
      issues and themes debated at the 1893 Congress and identify how the influence of
      Nightingale effected these discussions and the development of Western nursing for
      the next half-century.

PMID- 20807867
TI  - The effect of topical arnica on muscle pain.
AB  - BACKGROUND: The herb Arnica montana, in topical formulations, has been reputed to
      decrease bruising and muscle pain. This claim has been inadequately and
      incompletely addressed. OBJECTIVE: To determine whether topical A. montana cream
      could decrease subjective leg pain following calf raises. Secondary outcomes were
      effects on ankle range of motion and muscle tenderness. METHODS: A randomized,
      double-blind, placebo-controlled trial was conducted in 53 subjects. Active range
      of motion was measured in both ankles, and then a series of calf-raises were
      completed according to a standardized protocol. Each participant received 2 tubes
      of cream, 1 with active arnica and 1 with placebo. The creams were applied to the
      lower legs immediately after the exercise, and again at 24 and 48 hours
      postexercise according to the "RIGHT" or "LEFT" labels. At 48 hours postexercise,
      subjects had their ankle range of motion and muscle tenderness measured. Subjects
      used the analog scale to rate pain in each leg at baseline, 24 hours, 48 hours,
      and 72 hours. RESULTS: No significant differences in pain scores were seen before
      exercise (arnica: 0.07 vs placebo: 0.09, p = 0.32). Pain scores on legs treated
      with arnica were higher than scores on those receiving placebo 24 hours after
      exercise (3.04 vs 2.36, respectively; p < 0.005). Pain scores on day 3 (arnica:
      3.44 vs placebo: 3.20, p = 0.66) and day 4 (arnica: 2.36 vs placebo: 2.31, p =
      0.62) were not significantly different. There was no difference in muscle
      tenderness (arnica: 1.05 vs placebo: 1.05, p = 1.0). Ankle range of motion did
      not differ significantly on either day 1 (arnica: 64.70 degrees vs placebo:
      66.15, p = 0.352 or day 3 (arnica: 63.32 degrees vs placebo: 65.94, p = 0.058).
      CONCLUSIONS: Rather than decreasing leg pain, arnica was found to increase leg
      pain 24 hours after eccentric calf exercises. This effect did not extend to the
      48-hour measurement.

PMID- 20807868
TI  - Role of intrathecal rituximab and trastuzumab in the management of leptomeningeal
      carcinomatosis.
AB  - OBJECTIVE: To review evidence for the use of intrathecal rituximab and
      trastuzumab in the management of leptomeningeal carcinomatosis. DATA SOURCES: A
      search of MEDLINE (1966-July 2010) and International Pharmaceutical Abstracts
      (1970-July 2010) was performed using search terms intrathecal, trastuzumab,
      rituximab, and monoclonal antibody. Additionally, American Society of Clinical
      Oncology, San Antonio Breast Conference, American Association for Cancer
      Research, and American Society of Hematology meeting abstracts were searched.
      STUDY SELECTION AND DATA EXTRACTION: Publications were reviewed for inclusion.
      Those reporting use of rituximab and trastuzumab intrathecally are reviewed and
      include 1 Phase 1 trial, 2 small prospective studies, 1 case series, and 15 case
      reports. DATA SYNTHESIS: The treatment of leptomeningeal carcinomatosis is
      challenging due to the presence of the blood-brain barrier. Numerous systemically
      administered therapies do not readily penetrate into the site of leptomeningeal
      disease and have been ineffective. Intrathecal administration of 2 monoclonal
      antibodies (trastuzumab and rituximab) has been investigated in case reports and
      case series. Additionally, intrathecal rituximab has been investigated in a Phase
      1 study. Survival after intrathecal trastuzumab ranged from 39 days to greater
      than 72 months and the drug was well tolerated, with no adverse events attributed
      to it. Doses used in these reports ranged from 5 to 100 mg. Survival after
      intrathecal rituximab ranged from 1.1 weeks to greater than 3.5 years. In the
      Phase 1 trial, the maximum tolerated rituximab dose was 25 mg and 60% of patients
      responded. Four of the 6 responding patients experienced a complete response.
      Intrathecal rituximab exhibited minor toxicities that resolved quickly without
      long-term effects. CONCLUSIONS: Reports suggest that both trastuzumab and
      rituximab may be utilized intrathecally. Patients with refractory leptomeningeal
      carcinomatosis may benefit from a trial of intrathecal trastuzumab or rituximab;
      however, their use remains investigational, as more data and experience are
      necessary before intrathecal administration can be considered standard.

PMID- 20807869
TI  - Prognostic performance of metabolic indexes in predicting onset of type 1
      diabetes.
AB  - OBJECTIVE: In this investigation we evaluated nine metabolic indexes from
      intravenous glucose tolerance tests (IVGTTs) and oral glucose tolerance tests
      (OGTTs) in an effort to determine their prognostic performance in predicting the
      development of type 1 diabetes in those with moderate risk, as defined by
      familial relation to a type 1 diabetic individual, a positive test for islet cell
      antibodies and insulin autoantibody, but normal glucose tolerance. RESEARCH
      DESIGN AND METHODS: Subjects (n = 186) who had a projected risk of 25-50% for
      developing type 1 diabetes within 5 years were followed until clinical diabetes
      onset or the end of the study as part of the Diabetes Prevention Trial-Type 1.
      Prognostic performance of the metabolic indexes was determined using receiver
      operating characteristic (ROC) curve and survival analyses. RESULTS: Two-hour
      glucose from an OGTT most accurately predicted progression to disease compared
      with all other metabolic indicators with an area under the ROC curve of 0.67 (95%
      CI 0.59-0.76), closely followed by the ratio of first-phase insulin response
      (FPIR) to homeostasis model assessment of insulin resistance (HOMA-IR) with an
      area under the curve value of 0.66. The optimal cutoff value for 2-h glucose (114
      mg/dl) maintained sensitivity and specificity values >0.60. The hazard ratio for
      those with 2-h glucose >= 114 mg/dl compared with those with 2-h glucose <114
      mg/dl was 2.96 (1.67-5.22). CONCLUSIONS: The ratio of FPIR to HOMA-IR from an
      IVGTT provided accuracy in predicting the development of type 1 diabetes similar
      to that of 2-h glucose from an OGTT, which, because of its lower cost, is
      preferred. The optimal cutoff value determined for 2-h glucose provides
      additional guidance for clinicians to identify subjects for potential prevention
      treatments before the onset of impaired glucose tolerance.

PMID- 20807870
TI  - Magnesium intake in relation to systemic inflammation, insulin resistance, and
      the incidence of diabetes.
AB  - OBJECTIVE: To investigate the long-term associations of magnesium intake with
      incidence of diabetes, systemic inflammation, and insulin resistance among young
      American adults. RESEARCH DESIGN AND METHODS: A total of 4,497 Americans, aged 18
      30 years, who had no diabetes at baseline, were prospectively examined for
      incident diabetes based on quintiles of magnesium intake. We also investigated
      the associations between magnesium intake and inflammatory markers, i.e., high
      sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and fibrinogen,
      and the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS:
      During the 20-year follow-up, 330 incident cases of diabetes were identified.
      Magnesium intake was inversely associated with incidence of diabetes after
      adjustment for potential confounders. The multivariable-adjusted hazard ratio of
      diabetes for participants in the highest quintile of magnesium intake was 0.53
      (95% CI, 0.32-0.86; P(trend) < 0.01) compared with those in the lowest quintile.
      Consistently, magnesium intake was significantly inversely associated with hs
      CRP, IL-6, fibrinogen, and HOMA-IR, and serum magnesium levels were inversely
      correlated with hs-CRP and HOMA-IR. CONCLUSIONS: Magnesium intake was inversely
      longitudinally associated with incidence of diabetes in young American adults.
      This inverse association may be explained, at least in part, by the inverse
      correlations of magnesium intake with systemic inflammation and insulin
      resistance.

PMID- 20807871
TI  - Gestational diabetes mellitus alone in the absence of subsequent diabetes is
      associated with microalbuminuria: results from the Kidney Early Evaluation
      Program (KEEP).
AB  - OBJECTIVE: Women with gestational diabetes mellitus (GDM) maintain a higher risk
      for recurrent GDM and overt diabetes. Overt diabetes is a risk factor for
      development of chronic kidney disease (CKD), but GDM alone, without subsequent
      development of overt diabetes, may also pose a risk for CKD. RESEARCH DESIGN AND
      METHODS: This cross-sectional analysis included Kidney Early Evaluation Program
      (KEEP) participants from 2000 to 2009. Patient characteristics and kidney
      function among three categories (GDM alone, overt diabetes, and no history of
      diabetes) were compared. The prevalence of microalbuminuria, macroalbuminuria,
      and CKD stages 1-2 and 3-5 was assessed using logistic regression. RESULTS: Of
      37,716 KEEP female participants, 571 (1.5%) had GDM alone and 12,100 (32.1%) had
      overt diabetes. Women with GDM had a higher rate of microalbuminuria but not
      macroalbuminuria than their nondiabetic peers (10.0 vs. 7.7%) that was
      substantially lower than the 13.6% prevalence in diabetic women. In multivariate
      analysis, women with GDM alone, compared with nondiabetic women, demonstrated
      increased odds of CKD stages 1-2 (multivariate odds ratio 1.54 [95% CI 1.16
      2.05]) similar to the odds for women with overt diabetes (1.68 [1.55-1.82]). In
      stratified analyses, age, race, BMI, and hypertension modified the odds for CKD
      stages 1-2 but not CKD stages 3-5 among women with GDM. CONCLUSIONS: Women with
      GDM alone have a higher prevalence of microalbuminuria than women without any
      history of diabetes, translating to higher rates of CKD stages 1-2. These results
      suggest that GDM, even in the absence of subsequent overt diabetes, may increase
      the risk for future cardiovascular and kidney disease.

PMID- 20807872
TI  - Fewer major amputations among individuals with diabetes in Finland in 1997-2007:
      a population-based study.
AB  - OBJECTIVE: Complications occur in diabetes despite rigorous efforts to control
      risk factors. Since 2000, the National Development Programme for the Prevention
      and Care of Diabetes has worked to halve the incidence of amputations in 10
      years. Here we evaluate the impact of the efforts undertaken by analyzing the
      major amputations done in 1997-2007. RESEARCH DESIGN AND METHODS: All individuals
      with diabetes (n = 396,317) were identified from comprehensive national
      databases. Data on the first major amputations (n = 9,481) performed for diabetic
      and nondiabetic individuals were obtained from the National Hospital Discharge
      Register. RESULTS: The relative risk for the first major amputation was 7.4 (95%
      CI 7.2-7.7) among the diabetic versus the nondiabetic population. The
      standardized incidence of the first major amputation decreased among the diabetic
      and nondiabetic populations (48.8 and 25.2% relative risk reduction,
      respectively) over 11 years, and the time from the registration of diabetes to
      the first major amputation was significantly longer, on average 1.2 years more.
      The cumulative five-year postamputation mortality among diabetic individuals was
      78.7%. CONCLUSIONS: In our nationwide diabetes database, the duration from the
      registration of diabetes to the first major amputation increased, and the
      incidence of major amputations decreased almost 50% in 11 years. Approximately
      half of this change was due to the increasing size of the diabetic population.
      The risk for major amputation is more than sevenfold that among the nondiabetic
      population. These results pose a continuous challenge to improve diabetes care.

PMID- 20807873
TI  - Rates and determinants of coronary and abdominal aortic artery calcium
      progression in the Veterans Affairs Diabetes Trial (VADT).
AB  - OBJECTIVE: To determine the predictors of progression of calcified
      atherosclerosis and the effect of intensive glycemic control on this process in
      patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: As part of the Risk
      Factors, Atherosclerosis, and Clinical Events in Diabetes (RACED) substudy of the
      Veterans Affairs Diabetes Trial (VADT), 197 and 189 individuals with type 2
      diabetes received baseline and follow-up computed tomographic scans for
      measurement of coronary and abdominal artery calcium, respectively. Standard and
      novel risk factors were assessed at baseline, and progression of calcified
      atherosclerosis was determined by several methods. Progression was defined both
      as a categorical (square root increase of volumetric scores >= 2.5 mm(3)) and
      continuous variable. In addition, annualized percent change of volume scores was
      determined. RESULTS: After an average follow-up of 4.6 years, >75% of individuals
      demonstrated coronary (CAC) and abdominal artery calcification (AAC) progression.
      Progression increased with higher baseline calcium categories but was not
      influenced by standard risk factors. However, the albumin-to-creatinine ratio
      (ACR) (P = 0.02) and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) (P =
      0.01) predicted progression of CAC, and these results were not altered by
      adjustment for age and other traditional risk factors. Treatment assignment
      (intensive versus standard) within the VADT did not influence CAC or AAC
      progression, irrespective of baseline calcium category. CONCLUSIONS: In patients
      with long-standing type 2 diabetes, baseline CAC, Lp-PLA(2), and ACR predicted
      progression of CAC. Intensive glycemic control during the VADT did not reduce
      progression of calcified atherosclerosis.

PMID- 20807874
TI  - Aerobic exercise capacity and pulmonary function in athletes with and without
      type 1 diabetes.
AB  - OBJECTIVE: To compare the aerobic exercise capacity and pulmonary function
      between athletes with and without type 1 diabetes. RESEARCH DESIGN AND METHODS:
      Fifty-one adult age-matched individuals were assessed in random order to the
      maximum volume of O(2) consumption (Vo(2 peak max)) (ml/kg/min), anaerobic
      threshold (ml/kg/min), peak pulmonary ventilation (Ve), heart rate (beats per
      min), time to exhaustion (min), forced vital capacity (FEV) (%), forced
      expiratory volume in the first second (FEV1) (%), total lung capacity (TLC) (%),
      and lung diffusion capacity for carbon monoxide (DL(CO)) (%). Individuals were 27
      with type 1 diabetes: 15 athletes (ADM) and 12 nonathletes (NADM); and 24 healthy
      individuals: 12 ADM and 12 NADM. Duration of diabetes was 14.6 +/- 6.2 and 15.2
      +/- 6.7 years in ADM and NADM, respectively. RESULTS: Vo(2 peak) (max) was higher
      in ADM than in NADM (P < 0.001). The anaerobic threshold was lower in subjects
      with type 1 diabetes than in control subjects (P < 0.001). FEV1 was lower in ADM
      than in other groups (NADM, athletes control, and nonathletes control, P <
      0.001). CONCLUSIONS: Aerobic capacity in subjects with type 1 diabetes with
      programmed exercise is similar to the capacity of normal athletes despite lower
      anaerobic threshold and FEV1.

PMID- 20807875
TI  - Differences in cardiovascular risk profile of diabetic subjects discordantly
      classified by diagnostic criteria based on glycated hemoglobin and oral glucose
      tolerance test.
AB  - OBJECTIVE: To characterize the cardiovascular risk profile of subjects
      categorized differently by A1C- and oral glucose tolerance test (OGTT)-based
      diagnostic criteria for diabetes according to the recommendations of the American
      Diabetes Association (ADA). RESEARCH DESIGN AND METHODS: An OGTT, A1C, and
      several cardiovascular risk factors were assessed in 964 individuals without
      known diabetes participating in a cross-sectional epidemiological survey in Gran
      Canaria, Spain. RESULTS: Taking the OGTT as the gold standard, the sensitivity
      and specificity of an A1C value >= 6.5% were 38.7 and 99.6%, respectively.
      Subjects who fulfilled A1C-based criterion presented greater measures of BMI and
      waist circumference, lower values for HDL cholesterol, and higher values for
      fasting plasma glucose, homeostasis model assessment of insulin resistance, and
      fibrinogen than subjects with diabetic OGTT but A1C <6.5%. CONCLUSIONS: Newly
      diagnosed diabetic individuals who fulfill A1C-based diagnostic criterion for the
      disease display a more unfavorable cardiovascular risk profile than individuals
      who only meet the glucose-based criteria.

PMID- 20807876
TI  - What aspects of social network are protective for dementia? Not the quantity but
      the quality of social interactions is protective up to 15 years later.
AB  - OBJECTIVE: To test the association between several social networks variables
      reflecting both structural characteristics and quality of relationships with the
      risk of dementia and Alzheimer's disease 5 and up to 15 years later. METHODS: The
      study sample is gathered from the Paquid cohort, a French population-based study
      of 3,777 elderly people evaluated at baseline and regularly revisited during a 15
      year interval. The sample consisted of 2,089 subjects who completed the social
      network questionnaire and were free of dementia at the time of enrollment and
      also at the next two follow-ups to minimize the problem of reverse causality. The
      questionnaire collected at baseline included marital status, number of ties,
      nature of social network, satisfaction, perception of being
      understood/misunderstood, and reciprocity in relationships. RESULTS: The incident
      cases of dementia considered were those diagnosed at 5-year and subsequent follow
      ups, resulting in 461 dementia and 373 Alzheimer's disease cases. The
      multivariate Cox model, including the six social network variables and adjusted
      for numerous potential confounders, showed significant associations with
      satisfaction and reciprocity in relationships. Participants who felt satisfied
      with their relations had a 23% reduced dementia risk. Participants who reported
      that they received more support than they gave over their lifetime had a 55% and
      53% reduced risk for dementia and Alzheimer's disease, respectively. CONCLUSION:
      The only variables associated with subsequent dementia or Alzheimer's disease
      were those reflecting the quality of relationships. The delay between social
      network assessment and dementia diagnosis was from 5 up to 15 years, thus
      minimizing the problem of reverse causality.

PMID- 20807877
TI  - An international bioinformatics infrastructure to underpin the Arabidopsis
      community.
AB  - The future bioinformatics needs of the Arabidopsis community as well as those of
      other scientific communities that depend on Arabidopsis resources were discussed
      at a pair of recent meetings held by the Multinational Arabidopsis Steering
      Committee and the North American Arabidopsis Steering Committee. There are
      extensive tools and resources for information storage, curation, and retrieval of
      Arabidopsis data that have been developed over recent years primarily through the
      activities of The Arabidopsis Information Resource, the Nottingham Arabidopsis
      Stock Centre, and the Arabidopsis Biological Resource Center, among others.
      However, the rapid expansion in many data types, the international basis of the
      Arabidopsis community, and changing priorities of the funding agencies all
      suggest the need for changes in the way informatics infrastructure is developed
      and maintained. We propose that there is a need for a single core resource that
      is integrated into a larger international consortium of investigators. We
      envision this to consist of a distributed system of data, tools, and resources,
      accessed via a single information portal and funded by a variety of sources,
      under shared international management of an International Arabidopsis Informatics
      Consortium (IAIC). This article outlines the proposal for the development,
      management, operations, and continued funding for the IAIC.

PMID- 20807878
TI  - Arabidopsis VILLIN1 and VILLIN3 have overlapping and distinct activities in actin
      bundle formation and turnover.
AB  - Actin filament bundles are higher-order cytoskeletal structures that are crucial
      for the maintenance of cellular architecture and cell expansion. They are
      generated from individual actin filaments by the actions of bundling proteins
      like fimbrins, LIMs, and villins. However, the molecular mechanisms of dynamic
      bundle formation and turnover are largely unknown. Villins belong to the
      villin/gelsolin/fragmin superfamily and comprise at least five isovariants in
      Arabidopsis thaliana. Different combinations of villin isovariants are
      coexpressed in various tissues and cells. It is not clear whether these
      isovariants function together and act redundantly or whether they have unique
      activities. VILLIN1 (VLN1) is a simple filament-bundling protein and is Ca(2+)
      insensitive. Based on phylogenetic analyses and conservation of Ca(2+) binding
      sites, we predict that VLN3 is a Ca(2+)-regulated villin capable of severing
      actin filaments and contributing to bundle turnover. The bundling activity of
      both isovariants was observed directly with time-lapse imaging and total internal
      reflection fluorescence (TIRF) microscopy in vitro, and the mechanism mimics the
      "catch and zipper" action observed in vivo. Using time-lapse TIRF microscopy, we
      observed and quantified the severing of individual actin filaments by VLN3 at
      physiological calcium concentrations. Moreover, VLN3 can sever actin filament
      bundles in the presence of VLN1 when calcium is elevated to micromolar levels.
      Collectively, these results demonstrate that two villin isovariants have
      overlapping and distinct activities.

PMID- 20807879
TI  - Arabidopsis VILLIN5, an actin filament bundling and severing protein, is
      necessary for normal pollen tube growth.
AB  - A dynamic actin cytoskeleton is essential for pollen germination and tube growth.
      However, the molecular mechanisms underlying the organization and turnover of the
      actin cytoskeleton in pollen remain poorly understood. Villin plays a key role in
      the formation of higher-order structures from actin filaments and in the
      regulation of actin dynamics in eukaryotic cells. It belongs to the
      villin/gelsolin/fragmin superfamily of actin binding proteins and is composed of
      six gelsolin-homology domains at its core and a villin headpiece domain at its C
      terminus. Recently, several villin family members from plants have been shown to
      sever, cap, and bundle actin filaments in vitro. Here, we characterized a villin
      isovariant, Arabidopsis thaliana VILLIN5 (VLN5), that is highly and
      preferentially expressed in pollen. VLN5 loss-of-function retarded pollen tube
      growth and sensitized actin filaments in pollen grains and tubes to latrunculin
      B. In vitro biochemical analyses revealed that VLN5 is a typical member of the
      villin family and retains a full suite of activities, including barbed-end
      capping, filament bundling, and calcium-dependent severing. The severing activity
      was confirmed with time-lapse evanescent wave microscopy of individual actin
      filaments in vitro. We propose that VLN5 is a major regulator of actin filament
      stability and turnover that functions in concert with oscillatory calcium
      gradients in pollen and therefore plays an integral role in pollen germination
      and tube growth.

PMID- 20807880
TI  - The cytosolic tail dipeptide Ile-Met of the pea receptor BP80 is required for
      recycling from the prevacuole and for endocytosis.
AB  - Pea (Pisum sativum) BP80 is a vacuolar sorting receptor for soluble proteins and
      has a cytosolic domain essential for its intracellular trafficking between the
      trans-Golgi network and the prevacuole. Based on mammalian knowledge, we
      introduced point mutations in the cytosolic region of the receptor and produced
      chimeras of green fluorescent protein fused to the transmembrane domain of pea
      BP80 along with the modified cytosolic tails. By analyzing the subcellular
      location of these chimera, we found that mutating Glu-604, Asp-616, or Glu-620
      had mild effects, whereas mutating the Tyr motif partially redistributed the
      chimera to the plasma membrane. Replacing both Ile-608 and Met-609 by Ala (IMAA)
      led to a massive redistribution of fluorescence to the vacuole, indicating that
      recycling is impaired. When the chimera uses the alternative route, the IMAA
      mutation led to a massive accumulation at the plasma membrane. Using Arabidopsis
      thaliana plants expressing a fluorescent reporter with the full-length sequence
      of At VSR4, we demonstrated that the receptor undergoes brefeldin A-sensitive
      endocytosis. We conclude that the receptors use two pathways, one leading
      directly to the lytic vacuole and the other going via the plasma membrane, and
      that the Ileu-608 Met-609 motif has a role in the retrieval step in both
      pathways.

PMID- 20807881
TI  - Y3IP1, a nucleus-encoded thylakoid protein, cooperates with the plastid-encoded
      Ycf3 protein in photosystem I assembly of tobacco and Arabidopsis.
AB  - The intricate assembly of photosystem I (PSI), a large multiprotein complex in
      the thylakoid membrane, depends on auxiliary protein factors. One of the
      essential assembly factors for PSI is encoded by ycf3 (hypothetical chloroplast
      reading frame number 3) in the chloroplast genome of algae and higher plants. To
      identify novel factors involved in PSI assembly, we constructed an epitope-tagged
      version of ycf3 from tobacco (Nicotiana tabacum) and introduced it into the
      tobacco chloroplast genome by genetic transformation. Immunoaffinity purification
      of Ycf3 complexes from the transplastomic plants identified a novel nucleus
      encoded thylakoid protein, Y3IP1 (for Ycf3-interacting protein 1), that
      specifically interacts with the Ycf3 protein. Subsequent reverse genetics
      analysis of Y3IP1 function in tobacco and Arabidopsis thaliana revealed that
      knockdown of Y3IP1 leads to a specific deficiency in PSI but does not result in
      loss of Ycf3. Our data indicate that Y3IP1 represents a novel factor for PSI
      biogenesis that cooperates with the plastid genome-encoded Ycf3 in the assembly
      of stable PSI units in the thylakoid membrane.

PMID- 20807882
TI  - Hidden variability of floral homeotic B genes in Solanaceae provides a molecular
      basis for the evolution of novel functions.
AB  - B-class MADS box genes specify petal and stamen identities in several core
      eudicot species. Members of the Solanaceae possess duplicate copies of these
      genes, allowing for diversification of function. To examine the changing roles of
      such duplicate orthologs, we assessed the functions of B-class genes in Nicotiana
      benthamiana and tomato (Solanum lycopersicum) using virus-induced gene silencing
      and RNA interference approaches. Loss of function of individual duplicates can
      have distinct phenotypes, yet complete loss of B-class gene function results in
      extreme homeotic transformations of petal and stamen identities. We also show
      that these duplicate gene products have qualitatively different protein-protein
      interaction capabilities and different regulatory roles. Thus, compensatory
      changes in B-class MADS box gene duplicate function have occurred in the
      Solanaceae, in that individual gene roles are distinct, but their combined
      functions are equivalent. Furthermore, we show that species-specific differences
      in the stamen regulatory network are associated with differences in the
      expression of the microRNA miR169. Whereas there is considerable plasticity in
      individual B-class MADS box transcription factor function, there is overall
      conservation in the roles of the multimeric MADS box B-class protein complexes,
      providing robustness in the specification of petal and stamen identities. Such
      hidden variability in gene function as we observe for individual B-class genes
      can provide a molecular basis for the evolution of regulatory functions that
      result in novel morphologies.

PMID- 20807883
TI  - Impact of a statewide ST-segment-elevation myocardial infarction regionalization
      program on treatment times for women, minorities, and the elderly.
AB  - BACKGROUND: Prior studies have demonstrated differences in time to reperfusion
      for ST-segment-elevation myocardial infarction (STEMI) in women, minorities, and
      the elderly, relative to their counterparts. Regionalization has been shown to
      improve overall STEMI treatment times, but its impact on care differences among
      these important patient subgroups is unknown. The objective of this analysis was
      to assess the impact of a statewide system of STEMI care (The Reperfusion of
      Acute Myocardial Infarction in North Carolina Emergency Departments) on treatment
      times according to patient sex, race, and age. METHODS AND RESULTS: STEMI
      treatment times were determined before (July 2005 to September 2005) and after
      (January 2007 to March 2007) a year-long implementation of coordinated regional
      treatment protocols. Times in the pre- and postintervention periods were compared
      by mixed-effects models. A total of 2063 STEMI patients were analyzed: 1140 at
      percutaneous coronary intervention hospitals and 923 at non-percutaneous coronary
      intervention hospitals. The Reperfusion of Acute Myocardial Infarction in North
      Carolina Emergency Departments was associated with significant improvements in
      treatment times in women and the elderly, including door-to-ECG, door-to-device,
      door-in-door-out, and door-to-needle times (all P<0.05). Temporal improvements in
      treatment times at percutaneous coronary intervention hospitals were not
      significantly different in blacks than in whites. There was a reduction in
      baseline treatment disparities in door-to-ECG times in women versus men (4.4
      minute reduction in difference; 95% CI, -8.1 to -0.4; P=0.03). After Reperfusion
      of Acute Myocardial Infarction in North Carolina Emergency Departments, an age
      treatment time gap persisted in the elderly, relative to younger patients.
      CONCLUSIONS: A statewide STEMI regionalization program was associated with
      comparable improvement in treatment times for female, black, and elderly patients
      compared with middle-aged, white male patients. Nevertheless, there remain
      opportunities to further narrow treatment differences, particularly among the
      elderly.

PMID- 20807884
TI  - The effect of dietary patterns on estimated coronary heart disease risk: results
      from the Dietary Approaches to Stop Hypertension (DASH) trial.
AB  - BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) diet is
      recommended in the 2005 US Dietary Guidelines. To understand the potential
      benefits of DASH on coronary heart disease (CHD), we applied the Framingham risk
      equations to calculate 10-year risk of developing CHD using data from the DASH
      trial. METHODS AND RESULTS: In the DASH trial, 459 individuals with
      prehypertension or stage-1 hypertension not taking antihypertensive medication
      were randomly assigned to 1 of 3 diets: control, fruits and vegetables (F/V), or
      DASH (rich in fruits, vegetables, low-fat dairy, and reduced in fats and
      cholesterol). Weight was held constant. Estimated 10-year CHD risk was the
      primary outcome of this secondary analysis. Among 436 participants with complete
      data, mean (SD) age was 44.7 (10.7) years, 51% were male, and 60% were African
      American. Median 10-year CHD risk was 0.98% at baseline and decreased in all
      groups. Compared with control, the relative risk ratio comparing 8-week with
      baseline 10-year CHD risk was 0.93 (95% confidence interval, 0.85 to 1.02;
      P=0.12) for F/V and 0.82 (95% confidence interval, 0.75 to 0.90; P<0.001) for
      DASH. Comparing DASH with F/V, the relative risk ratio was 0.89 (95% confidence
      interval, 0.81 to 0.97; P=0.012). With the exception of an interaction between
      dietary pattern and race suggesting a greater risk reduction in blacks than
      whites (P for interaction=0.038), results were similar across subgroups.
      CONCLUSIONS: Compared with control and F/V, the DASH diet reduced estimated 10
      year CHD risk by 18% and 11%, respectively. In addition to reducing blood
      pressure, the DASH diet should substantially reduce the risk of CHD.

PMID- 20807885
TI  - Cells expressing FLT3/ITD mutations exhibit elevated repair errors generated
      through alternative NHEJ pathways: implications for genomic instability and
      therapy.
AB  - The internal tandem duplication (ITD) mutations of the FMS-like tyrosine kinase-3
      (FLT3) receptor found in acute myeloid leukemia patients are associated with poor
      prognosis. Although DNA double-strand breaks (DSBs) are mainly repaired by the
      DNA-PK-dependent nonhomologous end-joining (NHEJ) pathway in normal mammalian
      cells, an alternative and less well-defined NHEJ pathway, characterized by
      microhomology at the repair junctions, play a role in the generation of deletions
      and translocations leading to cancer progression. Here we report that in FLT3/ITD
      expressing cell lines and bone marrow mononuclear cells from FLT3/ITD knock-in
      mice, end-joining of DSBs occurs at microhomologous sequences resulting in a high
      frequency of DNA deletions. Strikingly, levels of Ku proteins, key components of
      the main NHEJ pathway, are decreased in FLT3/ITD(+) cell lines and murine
      FLT3/ITD bone marrow mononuclear cells. Concomitantly, levels of DNA ligase
      IIIalpha, a component of ALT NHEJ, are increased in FLT3/ITD-expressing cells.
      Cells treated with a FLT3 inhibitor demonstrate decreased DNA ligase IIIalpha and
      a reduction in DNA deletions, suggesting that FLT3 signaling regulates the
      pathways by which DSBs are repaired. Thus, therapy to inhibit FLT3/ITD signaling
      and/or DNA ligase IIIalpha may lead to repair that reduces repair errors and
      genomic instability.

PMID- 20807886
TI  - Dectin-1 Y238X polymorphism associates with susceptibility to invasive
      aspergillosis in hematopoietic transplantation through impairment of both
      recipient- and donor-dependent mechanisms of antifungal immunity.
AB  - The C-type lectin receptor Dectin-1 plays a pivotal role in antifungal immunity.
      In this study, the recently characterized human DECTIN1 Y238X early stop codon
      polymorphism leading to diminished Dectin-1 receptor activity was studied in
      relation to invasive aspergillosis susceptibility and severity in patients
      receiving hematopoietic stem cell transplantation. We found that the presence of
      the DECTIN1 Y238X polymorphism in either donors or recipients of hematopoietic
      stem cell transplantation increased susceptibility to aspergillosis, with the
      risk being highest when the polymorphism was present simultaneously in both
      donors and recipients (adjusted hazard ratio = 3.9; P = .005). Functionally, the
      Y238X polymorphism impaired the production of interferon-gamma and interleukin-10
      (IL-10), in addition to IL-1beta, IL-6, and IL-17A, by human peripheral
      mononuclear cells and Dectin-1 on human epithelial cells contributed to fungal
      recognition. Mechanistically, studies on preclinical models of infection in
      intact or bone marrow-transplanted Dectin-1 knockout mice revealed that
      protection from infection requires a distinct, yet complementary, role of both
      donor and recipient Dectin-1. This study discloses Dectin-1 deficiency as a novel
      susceptibility factor for aspergillosis in high-risk patients and identifies a
      previously unsuspected role for Dectin-1 in antifungal immunity that is the
      ability to control both resistance and tolerance to the fungus contingent on
      hematopoietic/nonhematopoietic compartmentalization.

PMID- 20807887
TI  - TEL-AML1 regulation of survivin and apoptosis via miRNA-494 and miRNA-320a.
AB  - There is increasing evidence that miRNA and transcription factors interact in an
      instructive fashion in normal and malignant hematopoiesis. We explored the impact
      of TEL-AML1 (ETV6-RUNX1), the most common fusion protein in childhood leukemia,
      on miRNA expression and the leukemic phenotype. Using RNA interference, miRNA
      expression arrays, and quantitative polymerase chain reaction, we identified
      miRNA-494 and miRNA-320a to be up-regulated upon TEL-AML1 silencing independently
      of TEL expression. Chromatin immunoprecipitation analysis identified miRNA-494 as
      a direct miRNA target of the fusion protein TEL-AML1. Using bioinformatic
      analysis as well as functional luciferase experiments, we demonstrate that
      survivin is a target of the 2 miRNAs. miRNA-494 and miRNA-320a were introduced to
      the cells by transfection and survivin expression determined by Western blot
      analysis. These miRNAs blocked survivin expression and resulted in apoptosis in a
      similar manner as TEL-AML1 silencing by itself; this silencing was also shown to
      be Dicer-dependent. miRNAs-494 and -320a are expressed at lower levels in TEL
      AML1+ leukemias compared with immunophenotype-matched nonTEL-AML1 acute
      lymphoblastic leukemia subtypes, and within TEL-AML1+ leukemias their expression
      is correlated to survivin levels. In summary our data suggest that TEL-AML1 might
      exert its antiapoptotic action at least in part by suppressing miRNA-494 and
      miRNA-320a, lowering their expression causing enhanced survivin expression.

PMID- 20807888
TI  - BCOR as a novel fusion partner of retinoic acid receptor alpha in a
      t(X;17)(p11;q12) variant of acute promyelocytic leukemia.
AB  - The majority of acute promyelocytic leukemia (APL) cases are characterized by the
      presence of a promyelocytic leukemia-retinoic acid receptor alpha(RARA) fusion
      gene. In a small subset, RARA is fused to a different partner, usually involved
      in regulating cell growth and differentiation. Here, we identified a novel RARA
      fusion transcript, BCOR-RARA, in a t(X;17)(p11;q12) variant of APL with unique
      morphologic features, including rectangular and round cytoplasmic inclusion
      bodies. Although the patient was clinically responsive to all-trans retinoic
      acid, several relapses occurred with standard chemotherapy and all-trans retinoic
      acid. BCOR is a transcriptional corepressor through the proto-oncoprotein, BCL6,
      recruiting histone deacetylases and polycomb repressive complex 1 components.
      BCOR-RARA was found to possess common features with other RARA fusion proteins.
      These included: (1) the same break point in RARA cDNA; (2) self-association; (3)
      retinoid X receptor alpha is necessary for BCOR-RARA to associate with the RARA
      responsive element; (4) action in a dominant-negative manner on RARA
      transcriptional activation; and (5) aberrant subcellular relocalization. It
      should be noted that there was no intact BCOR found in the 45,-Y,t(X;17)(p11;q12)
      APL cells because they featured only a rearranged X chromosome. These results
      highlight essential features of pathogenesis in APL in more detail. BCOR appears
      to be involved not only in human congenital diseases, but also in a human cancer.

PMID- 20807889
TI  - Bone marrow myeloid-derived suppressor cells (MDSCs) inhibit graft-versus-host
      disease (GVHD) via an arginase-1-dependent mechanism that is up-regulated by
      interleukin-13.
AB  - Myeloid-derived suppressor cells (MDSCs) are a well-defined population of cells
      that accumulate in the tissue of tumor-bearing animals and are known to inhibit
      immune responses. Within 4 days, bone marrow cells cultured in granulocyte colony
      stimulating factor and granulocyte-macrophage colony-stimulating factor resulted
      in the generation of CD11b(+)Ly6G(lo)Ly6C(+) MDSCs, the majority of which are
      interleukin-4Ralpha (IL-4Ralpha(+)) and F4/80(+). Such MDSCs potently inhibited
      in vitro allogeneic T-cell responses. Suppression was dependent on L-arginine
      depletion by arginase-1 activity. Exogenous IL-13 produced an MDSC subset (MDSC
      IL-13) that was more potently suppressive and resulted in arginase-1 up
      regulation. Suppression was reversed with an arginase inhibitor or on the
      addition of excess L-arginine to the culture. Although both MDSCs and MDSC-IL-13
      inhibited graft-versus-host disease (GVHD) lethality, MDSC-IL-13 were more
      effective. MDSC-IL-13 migrated to sites of allopriming. GVHD inhibition was
      associated with limited donor T-cell proliferation, activation, and
      proinflammatory cytokine production. GVHD inhibition was reduced when arginase-1
      deficient MDSC-IL-13 were used. MDSC-IL-13 did not reduce the graft-versus
      leukemia effect of donor T cells. In vivo administration of a pegylated form of
      human arginase-1 (PEG-arg1) resulted in L-arginine depletion and significant GVHD
      reduction. MDSC-IL-13 and pegylated form of human arginase-1 represent novel
      strategies to prevent GVHD that can be clinically translated.

PMID- 20807890
TI  - Lineage-instructive function of C/EBPalpha in multipotent hematopoietic cells and
      early thymic progenitors.
AB  - Hematopoiesis is tightly controlled by transcription regulatory networks, but how
      and when specific transcription factors control lineage commitment are still
      largely unknown. Within the hematopoietic stem cell (Lin(-)Sca-1(+)c-Kit(+))
      compartment these lineage-specific transcription factors are expressed at low
      levels but are up-regulated with the process of lineage specification.
      CCAAT/enhancer binding protein alpha (C/EBPalpha) represents one of these factors
      and is involved in myeloid development and indispensable for formation of
      granulocytes. To track the cellular fate of stem and progenitor cells, which
      express C/EBPalpha, we developed a mouse model expressing Cre recombinase from
      the Cebpa promoter and a conditional EYFP allele. We show that Cebpa/EYFP(+)
      cells represent a significant subset of multipotent hematopoietic progenitors,
      which predominantly give rise to myeloid cells in steady-state hematopoiesis.
      C/EBPalpha induced a strong myeloid gene expression signature and down-regulated
      E2A-induced regulators of early lymphoid development. In addition, Cebpa/EYFP(+)
      cells compose a fraction of early thymic progenitors with robust myeloid
      potential. However, Cebpa/EYFP(+) multipotent hematopoietic progenitors and early
      thymic progenitors retained the ability to develop into erythroid and T-lymphoid
      lineages, respectively. These findings support an instructive but argue against a
      lineage-restrictive role of C/EBPalpha in multipotent hematopoietic and thymic
      progenitors.

PMID- 20807891
TI  - Inhibition of the intrinsic coagulation pathway factor XI by antisense
      oligonucleotides: a novel antithrombotic strategy with lowered bleeding risk.
AB  - Existing anticoagulants effectively inhibit the activity of coagulation factors
      of the extrinsic and common pathway but have substantial limitations and can
      cause severe bleeding complications. Here we describe a novel therapeutic
      approach to thrombosis treatment. We have developed and characterized the
      efficacy and safety of selective second-generation antisense oligonucleotides
      (ASOs) targeting coagulation factor XI (FXI), a member of the intrinsic
      coagulation pathway. Systemic treatment of mice with FXI ASO led to a potent,
      specific, and dose-dependent reduction of FXI mRNA levels in the liver with
      corresponding reductions in plasma levels of FXI protein and activity. FXIASO
      treatment produced potent, dose-dependent antithrombotic activity in various
      venous and arterial thrombosis models, comparable with warfarin or enoxaparin.
      However, unlike warfarin or enoxaparin, FXI inhibition did not cause bleeding.
      Coadministration of FXI ASO with enoxaparin or the antiplatelet drug clopidogrel
      produced improved antithrombotic activity without increased bleeding. Finally,
      plasma-derived FXI concentrate was shown to effectively and rapidly reverse the
      anticoagulant effect of FXI antisense therapy. These results support the concept
      that inhibition of FXI through antisense therapy might serve as a new and
      effective strategy for the treatment and prevention of venous thromboembolism
      with improved specificity and safety.

PMID- 20807893
TI  - Promoting effective communication for patients receiving mechanical ventilation.
AB  - Communicating effectively with ventilator-dependent patients is essential so that
      various basic physiological and psychological needs can be conveyed and
      decisions, wishes, and desires about the plan of care and end-of-life decision
      making can be expressed. Numerous methods can be used to communicate, including
      gestures, head nods, mouthing of words, writing, use of letter/picture boards and
      common words or phrases tailored to meet individualized patients' needs. High
      tech alternative communication devices are available for more complex cases.
      Various options for patients with a tracheostomy tube include partial or total
      cuff deflation and use of a speaking valve. It is important for nurses to assess
      communication needs; identify appropriate alternative communication strategies;
      create a customized care plan with the patient, the patient's family, and other
      team members; ensure that the care plan is visible and accessible to all staff
      interacting with the patient; and continue to collaborate with colleagues from
      all disciplines to promote effective communication with nonvocal patients.

PMID- 20807892
TI  - Efficacy and safety of once-weekly bortezomib in multiple myeloma patients.
AB  - In a recent phase 3 trial, bortezomib-melphalan-prednisone-thalidomide followed
      by maintenance treatment with bortezomib-thalidomide demonstrated superior
      efficacy compared with bortezomib-melphalan-prednisone. To decrease neurologic
      toxicities, the protocol was amended and patients in both arms received once
      weekly instead of the initial twice-weekly bortezomib infusions: 372 patients
      received once-weekly and 139 twice-weekly bortezomib. In this post-hoc analysis
      we assessed the impact of the schedule change on clinical outcomes and safety.
      Long-term outcomes appeared similar: 3-year progression-free survival rate was
      50% in the once-weekly and 47% in the twice-weekly group (P > .999), and 3-year
      overall survival rate was 88% and 89%, respectively (P = .54). The complete
      response rate was 30% in the once-weekly and 35% in the twice-weekly group (P =
      .27). Nonhematologic grade 3/4 adverse events were reported in 35% of once-weekly
      patients and 51% of twice-weekly patients (P = .003). The incidence of grade 3/4
      peripheral neuropathy was 8% in the once-weekly and 28% in the twice-weekly group
      (P < .001); 5% of patients in the once-weekly and 15% in the twice-weekly group
      discontinued therapy because of peripheral neuropathy (P < .001). This
      improvement in safety did not appear to affect efficacy. This study is registered
      at http://www.clinicaltrials.gov as NCT01063179.

PMID- 20807894
TI  - Determination of total homocysteine, methylmalonic acid, and 2-methylcitric acid
      in dried blood spots by tandem mass spectrometry.
AB  - BACKGROUND: Newborn screening (NBS) for inborn errors of propionate, methionine,
      and cobalamin metabolism relies on finding abnormal concentrations of methionine
      and propionylcarnitine. These analytes are not specific for these conditions and
      lead to frequent false-positive results. More specific markers are total
      homocysteine (tHCY), methylmalonic acid (MMA), and methylcitric acid (MCA), but
      these markers are not detected by current NBS methods. To improve this situation,
      we developed a method for the detection of tHCY, MMA, and MCA in dried blood
      spots (DBSs) by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
      METHODS: The analytes were extracted from a single 4.8-mm DBS punch with
      acetonitrile:water:formic acid (59:41:0.42) containing dithiothreitol and
      isotopically labeled standards (d(3)-MMA, d(3)-MCA, d(8)-homocystine). The
      extract was dried and treated with 3 N HCl in n-butanol to form butylesters.
      After evaporation of the butanol, the residue was reconstituted and centrifuged
      and the supernatant was subjected to LC-MS/MS analysis. Algorithms were developed
      to apply this method as an efficient and effective second-tier assay on samples
      with abnormal results by primary screening. RESULTS: The 99th percentiles
      determined from the analysis of 200 control DBSs for MMA, MCA, and HCY were 1.5,
      0.5, and 9.8 MUmol/L, respectively. Since 2005, prospective application of this
      second-tier analysis to 2.3% of all NBS samples led to the identification of 13
      affected infants. CONCLUSIONS: Application of this assay reduced the false
      positive rate and improved the positive predictive value of NBS for conditions
      associated with abnormal propionylcarnitine and methionine concentrations.

PMID- 20807895
TI  - Deconstructing early life experiences: distinguishing the contributions of
      prenatal and postnatal factors to adult male sexual behavior in the rat.
AB  - In rodents, a pup's experiences in utero and during postnatal development shape
      its sexual behavior as an adult and how it is perceived by potential mates. We
      show that the male rat's sexuality is primarily influenced by the postnatal sex
      ratio of its litter, but not by the litter's prenatal intrauterine sex ratio or
      the behavior of its mother. Pups from litters with differing prenatal sex ratios
      were divided into litters with differing postnatal sex ratios. We found that
      males raised in a female-biased litter exhibited less mounting than males raised
      in either a male-biased litter or one with an equal sex ratio, and were less
      attractive to sexually receptive females, eliciting fewer soliciting behaviors,
      such as hop-darts, and fewer lordosis behaviors. However, the number of
      intromissions and ejaculations did not differ across groups, which suggests that
      males from female-biased litters mate as efficiently as males raised in other sex
      ratios, but do not require as many mounts to do so. The reported differences in
      sexual behavior did not vary with the quality of maternal behavior or with sexual
      experience in adulthood.

PMID- 20807896
TI  - Direct evidence for the role of inhibition in resolving interference in memory.
AB  - Interference from competing material at retrieval is a major cause of memory
      failure. We tested the hypothesis that such interference can be overcome by
      suppressing competing responses. In a three-phase task, participants in the
      critical interference condition first performed a vowel-counting task (Phase 1)
      that included pairs of orthographically similar words (e.g., allergy and
      analogy). After a delay, participants were asked to solve word fragments (e.g., a
      _ l _ _ gy) that resembled both words in a pair they had seen, but could be
      completed only by one of these words (Phase 2). We then measured the consequence
      of having successfully resolved interference in Phase 2 by asking participants to
      read a list of words, including rejected competitor words (i.e., the word in each
      pair that could not be used to solve the word fragments), as quickly as possible
      (Phase 3). Participants in the interference condition were slower to name the
      competitor words than participants in conditions that did not require
      interference resolution. These results constitute direct evidence for the role of
      active suppression in resolving interference during memory retrieval.

PMID- 20807897
TI  - Distorting, misrepresenting and slanting research results.

PMID- 20807899
TI  - Pacemakers and dental devices.

PMID- 20807898
TI  - Findings questioned.

PMID- 20807900
TI  - More about pacemakers.

PMID- 20807901
TI  - Eating disorders.

PMID- 20807902
TI  - Dr. Jane Weintraub receives Norton M. Ross award for excellence in clinical
      research.

PMID- 20807905
TI  - Is there a relationship between asthma and dental caries?: a critical review of
      the literature.
AB  - BACKGROUND: The authors conducted a critical review of the literature to
      ascertain the strength of the scientific and professional evidence supporting an
      association between dental caries and the experience and severity of asthma.
      TYPES OF STUDIES REVIEWED: In March 2010, the authors searched Medline (1976
      2010) by using the Ovid Web Gateway for the terms "asthma" and ["dental caries"
      or "dental caries susceptibility"] appearing in studies of humans published in
      English. The authors eliminated conference proceedings and abstracts, opinion
      pieces and unpublished studies; they included case series, cross-sectional, case
      control and cohort studies and clinical trials. RESULTS: The review yielded 27
      studies described in 29 articles. The authors found that researchers have
      investigated the hypothesized relationship between asthma and caries by means of
      diverse strategies, often using asthma cases clustered in pools of patients
      seeking clinical care. The strongest methodological designs were more likely to
      reveal little support for a positive association. The authors found no strong
      evidence suggesting that a causal link exists. Future research incorporating
      better-defined covariates and longitudinal designs is needed. CLINICAL
      IMPLICATIONS: Asthma per se may not be a risk factor for caries. Patients who
      have extreme dryness of the mouth, whose use of nebulizers is persistent, whose
      consumption of carbohydrates is frequent, and who have used multiple medications
      or have used medications over the long term necessitate cautious dental health
      care.

PMID- 20807906
TI  - Bifid mandibular condyle: a disorder in its own right?
AB  - BACKGROUND: The authors present six cases of mandibular condyle malformation.
      They also conducted a literature review of bifid mandibular condyle (BMC) to
      analyze the various hypotheses that have been made regarding the etiopathogenesis
      of this entity. Type of Studies Reviewed. The authors searched the PubMed
      database for all instances of BMC and similar anatomical alterations, and they
      included non-English-language published reports. The inclusion criterion was the
      presence of a multilobular mandibular condyle. RESULTS: Mandibular condyle may
      manifest in different anatomical forms; bilobular is the most common, although
      triple lobular morphology also has been observed. A congenital origin has been
      suggested as the primary cause. In addition, trauma may alter the growth of the
      condylar cartilage, inducing an anatomical defect. However, the majority of
      participants in this study had no history of trauma. The authors reviewed a total
      of 198 cases in study participants and cadavers. CLINICAL IMPLICATIONS: In the
      absence of traumatic antecedents or other alterations of the temporomandibular
      joint, the presence of a BMC may be associated with developmental anomalies.

PMID- 20807907
TI  - Managing the care of patients with temporomandibular disorders: a new guideline
      for care.

PMID- 20807908
TI  - Dysphagia and submandibular swelling. Eagle syndrome.

PMID- 20807909
TI  - Neurovascular orofacial pain.

PMID- 20807910
TI  - Treating dentin hypersensitivity: therapeutic choices made by dentists of the
      northwest PRECEDENT network.
AB  - BACKGROUND: Methods used by dental practitioners to diagnose and treat dentin
      hypersensitivity are not well documented. The authors conducted a survey of
      dentists in the Northwest Practice-based REsearch Collaborative in Evidence-based
      DENTistry (PRECEDENT) to ascertain the treatment methods they used. Methods. Via
      an Internet survey, the authors collected data regarding methods used for
      diagnosis and treatment of dentin hypersensitivity from 209 Northwest PRECEDENT
      dentists. RESULTS: The PRECEDENT dentists indicated that they most often used
      fluoride varnishes and gels, advice regarding toothbrushing and diet, bonding
      agents, restorative materials and glutaraldehyde/2-hydroxyethyl methacrylate
      (HEMA) to treat dentin hypersensitivity. They reported that the most successful
      treatments were fluorides, glutaraldehyde/HEMA, bonding agents, potassium
      nitrates and restorative treatments; they considered observation, advice
      regarding toothbrushing and diet and laser therapy to be the least successful.
      Dentists listed fluorides, calcium phosphates, glutaraldehyde/HEMA and bonding
      agents as the treatments most desirable for inclusion in a future randomized
      clinical trial of dental hypersensitivity treatments. CONCLUSIONS: Dentists rely
      on patients to assess the severity of dentin hypersensitivity. Modalities for the
      diagnosis and treatment of hypersensitivity are diverse. Methods used to diagnose
      and treat dentin hypersensitivity in practice are challenging to justify.
      CLINICAL IMPLICATIONS: Practitioners should be aware of the diversity of methods
      available for diagnosing and treating dentin hypersensitivity as they manage the
      care of their patients with this condition.

PMID- 20807911
TI  - Outcomes in patients hospitalized for periapical abscess in the United States: an
      analysis involving the use of a nationwide inpatient sample.
AB  - BACKGROUND: Severe infections resulting from periapical abscesses may warrant
      hospitalization. The authors conducted a study to investigate the factors
      affecting outcomes for patients hospitalized for periapical abscess in the United
      States in 2007. METHODS: The authors used the Nationwide Inpatient Sample of the
      Healthcare Cost and Utilization Project for 2007. They selected for analysis all
      hospitalizations attributed primarily to periapical abscess. Outcomes examined
      included hospitalization charges, length of stay and type of admission (emergency
      or urgent versus elective). They used multivariable regression analysis to
      examine the effects of patient-related factors (including age, sex, presence of
      comorbid conditions, insurance status, type of periapical abscess and discharge
      disposition) on outcomes. RESULTS: In 2007, 7,886 hospitalizations were
      attributed primarily to periapical abscess. Total hospital charges were $105.8
      million. Periapical abscess also resulted in a total of 23,001 hospitalization
      days. The mean hospitalization charges and length of stay were $13,590 and 2.92
      days, respectively. The authors found an association between patients with
      comorbid conditions and higher charges and longer length of stay (P < .05). Of
      all hospitalizations, 91 percent occurred on an emergency or urgent basis. The
      percentage was significantly higher among uninsured patients than among those
      with private insurance (P < .05). CONCLUSION: The study provides nationally
      representative estimates of outcomes associated with hospitalizations due to
      periapical abscess, and it highlights the substantial resources needed to treat
      patients hospitalized for this condition.

PMID- 20807912
TI  - Oral hygiene can reduce the incidence of and death resulting from pneumonia and
      respiratory tract infection.

PMID- 20807914
TI  - Addressing disagreements in partnerships.

PMID- 20807915
TI  - What ethical issues should general dentists consider when the state of the
      economy affects decisions regarding referral of patients to specialists?

PMID- 20807918
TI  - For the dental patient ... Acetaminophen overdose and liver damage.

PMID- 20807919
TI  - Driving with an arm immobilized in a splint: a randomized higher-order crossover
      trial.
AB  - BACKGROUND: The aim of this study was to determine whether immobilization of an
      arm has detrimental effects on driving performance. METHODS: Thirty-six healthy
      officers-in-training were assigned a sequence of fiberglass splints (left and
      right-sided above-the-elbow thumb spica and below-the-elbow splints) with use of
      a randomized higher-order crossover design. Runs were scored on a cone-marked
      driving course used for officer certification with predetermined passing
      requirements. Driving time, the number of cones hit per course section, and the
      cone-adjusted total time (a five-second penalty per hit cone) were recorded. A
      linear mixed-effect model with random environmental and learning effects for cone
      adjusted time analysis was used. Participants rated perceived driving difficulty
      and safety with each splint, and ratings were compared with the Wilcoxon signed
      rank test. RESULTS: Thirty participants completed the entire set of runs.
      Analysis of total cone-adjusted time revealed a significant performance decrease
      with the left arm in an above-the-elbow thumb spica splint (average, 22.2
      seconds; p < 0.001) and with the left arm in a below-the-elbow splint (average,
      16.2; p = 0.007). Analysis of forward-only course sections revealed poorer
      performance trends with all splints, with the worst performance with the left arm
      in an above-the-elbow thumb spica splint. Driving with the left arm in an above
      the-elbow thumb spica splint had the highest perceived difficulty (median, 8.0)
      and lowest perceived safety (median, 3.0). CONCLUSIONS: Driving performance as
      measured with a standardized track and scoring system was significantly degraded
      with splint immobilization of the left arm. Further studies are required to
      determine the effect of arm immobilization on normal driving conditions.

PMID- 20807920
TI  - Correlation between Herrold egg yolk medium culture and real-time quantitative
      polymerase chain reaction results for Mycobacterium avium subspecies
      paratuberculosis in pooled fecal and environmental samples.
AB  - Real-time quantitative polymerase chain reaction (qPCR) testing for Mycobacterium
      avium subspecies paratuberculosis (MAP) in fecal samples is a rapid alternative
      to culture on Herrold egg yolk medium (HEYM), the traditional antemortem
      reference test for MAP. Although the sensitivity and specificity of these 2 tests
      have been estimated based on dichotomized test results, the correlation between
      real-time qPCR threshold cycle (Ct) values and colony-forming units (CFU) on HEYM
      for fresh and thawed samples has not been evaluated. The objectives of the
      present study were to estimate the correlation and association between Ct and CFU
      in fresh and thawed pooled fecal and environmental samples. Results of HEYM
      culture of 1,997 pooled fecal samples from cows in 14 herds, and 802
      environmental samples from 109 dairies nationwide were negatively (inversely)
      correlated with their respective real-time qPCR results. The Spearman's rank
      correlation between Ct and CFU was good (-0.66) in fresh and thawed pooled fecal
      samples, and excellent (-0.76) and good (-0.61) in fresh and thawed environmental
      samples, respectively. The correlation varied from good (-0.53) to excellent (
      0.90) depending on the number of samples in a fecal pool. Truncated regression
      models indicated a significant negative association between Ct and CFU in fecal
      pools and environmental samples. The use of real-time qPCR instead of HEYM can
      yield rapid, quantitative estimates of MAP load and allow for incorporation of
      real-time qPCR results of pooled and environmental samples in testing strategies
      to identify dairy cow groups with the highest MAP shedding.

PMID- 20807921
TI  - Detection of PrP(Sc) in formalin-fixed, paraffin-embedded tissue by Western blot
      differentiates classical scrapie, Nor98 scrapie, and bovine spongiform
      encephalopathy.
AB  - Transmissible, spongiform encephalopathies including bovine spongiform
      encephalopathy (BSE) and scrapie are fatal neurodegenerative disorders associated
      with the presence of an infectious abnormal isoform of normal mammalian proteins
      called prions. Identification of the prion protein associated with scrapie
      (PrP(Sc)) in the central nervous system is typically based upon immunoassays
      including immunohistochemistry (IHC) using formalin-fixed tissues or Western blot
      (WB) assays using fresh and/or frozen, non-formalin-fixed tissues. Each assay can
      discriminate between BSE, classical scrapie, and a previously reported strain of
      scrapie recently identified in the United States named Nor98 scrapie. Different
      tissue samples are required from the same animal to run these 2 different
      immunoassays. This may result in inconsistent test results for the same animal.
      Sampling problems such as collecting insufficient volumes of fresh tissue or less
      than optimal anatomic location of brainstem for IHC can affect the ability of the
      test procedures to offer definitive and discriminatory results. Recently, a WB
      method using formalin-fixed, paraffin-embedded (FFPE) tissue to identify PrP(Sc)
      was developed that successfully identified PrP(Sc) in sheep affected by classical
      scrapie. In the current study, the use of this technique to produce
      discriminatory results identifying classical BSE in bovine tissue and both
      classical and Nor98 scrapie in ovine tissue using paraffin-embedded brain samples
      is described. Protein-banding patterns from WB using FFPE tissue were similar to
      protein-banding patterns produced by WB assays utilizing fresh tissues from the
      same animals, and results correlated well with the IHC PrP(Sc)-positive staining
      present in the cerebellum and obex regions of brain samples from these animals.

PMID- 20807922
TI  - Canine reference intervals for coagulation markers using the STA Satellite(R) and
      the STA-R Evolution(R) analyzers.
AB  - The aim of the current study was to determine canine reference intervals for
      prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen,
      and antithrombin (AT) according to international recommendations. The STA
      Satellite(R) coefficients of variation of within-laboratory imprecision were
      3.9%, 1.3%, 6.9%, and 5.1% for PT, APTT, fibrinogen, and AT, respectively. At 4
      degrees C, citrated specimens were stable up to 8 hr for whole blood and 36 hr
      for plasma, except for APTT, which increased slightly (<1 sec). Nonparametric
      reference intervals determined in citrated plasma from 139 healthy fasting
      purebred dogs were 6.9-8.8 sec, 13.1-17.2 sec, 1.24-4.30 g/l, and 104-188% for
      PT, APTT, fibrinogen, and AT, respectively. Based on Passing-Bablok comparison
      between STA Satellite and STA-R Evolution(R) using 60 frozen specimens from a
      canine plasma bank, the corresponding reference intervals were transferred to the
      STA-R Evolution: 7.1-9.2 sec, 12.9-17.3 sec, 1.20-4.43 g/l, and 94-159% for PT,
      APTT, fibrinogen, and AT, respectively.

PMID- 20807923
TI  - An investigation of blood selenium concentrations of goats in New York State.
AB  - The goal of the current study was to determine the range of blood selenium
      concentrations in goats in New York State that were fed adequately supplemented
      diets. Blood samples from mature, juvenile, and neonatal goats from commercial
      farms, 2 dairy and 2 meat producers, were analyzed via graphite-furnace atomic
      absorption spectroscopy. Feed samples were analyzed by using inductively coupled
      argon plasma optical emission spectroscopy to confirm that dietary selenium
      concentrations were adequate. The ranges of blood selenium concentration obtained
      were 9.1-49.9 microg/dl for mature goats, 7.6-37.5 microg/dl for juveniles, and
      9.7-40.7 microg/dl for neonates.

PMID- 20807924
TI  - Effect of pancreatic tissue sampling on serum pancreatic enzyme levels in
      clinically healthy dogs.
AB  - Little is known about the potential consequences of pancreatic tissue sampling in
      dogs. The goal of the present study was to evaluate changes in serum trypsin-like
      immunoreactivity and canine-specific pancreatic lipase after pancreatic fine
      needle aspiration and surgical biopsy in 27 clinically healthy dogs. Presurgical,
      ultrasound-guided aspiration of the pancreas was performed with the dogs under
      sedation. Subsequently, all the dogs underwent intraoperative pancreatic fine
      needle aspiration and clamshell biopsy. After euthanasia, pancreata were
      sectioned for histopathologic evaluation. Serum pancreatic enzyme levels were
      measured at 3 time points: baseline, after ultrasound-guided aspiration, and
      after intraoperative aspiration and biopsy. No significant differences were
      detected among mean serum pancreatic lipase values at any point (P > 0.05). Serum
      trypsin-like immunoreactivity did not change from baseline (18.2 +/- 2.1
      microg/dl; mean +/- standard error) after ultrasound-guided aspiration (13.6 +/-
      2.2 microg/dl) but increased significantly after intraoperative sampling (44.8 +/
      1.9 microg/dl; P < 0.0005). After surgical biopsy, the 20 dogs that had both
      ultrasound-guided and intraoperative sampling had a higher mean (SE) serum
      trypsin-like immunoreactivity (44.8 +/- 1.9 microg/dl) than the 7 dogs that had
      only intraoperative samples taken (36.4 +/- 4.1 microg/dl; P < 0.05). All 27
      pancreata were grossly normal before intraoperative sampling. Pancreatic sampling
      was associated with increased serum trypsin-like immunoreactivity and mild,
      peracute necrosis, inflammation, hemorrhage, and fibrin deposition. Tissue damage
      from sampling was not sufficient to cause an elevation in canine-specific
      pancreatic lipase in the time frame evaluated. Further studies are needed to
      determine longer-term effects of pancreatic sampling on enzyme levels and
      clinical outcome.

PMID- 20807925
TI  - A novel rapid genotyping technique for Collie eye anomaly: SYBR Green-based real
      time polymerase chain reaction method applicable to blood and saliva specimens on
      Flinders Technology Associates filter paper.
AB  - Collie eye anomaly (CEA) is a canine inherited ocular disease that shows a wide
      variety of manifestations and severity of clinical lesions. Recently, a CEA
      associated mutation was reported, and a DNA test that uses conventional
      polymerase chain reaction (PCR) has now become available. The objective of the
      current study was to develop a novel rapid genotyping technique by using SYBR
      Green-based real-time PCR for future large-scale surveys as a key part in the
      strategy to eradicate CEA by selective breeding. First, a SYBR Green-based real
      time PCR assay for genotyping of CEA was developed and evaluated by using
      purified DNA samples from normal, carrier, and affected Border Collies in which
      genotypes had previously been determined by conventional PCR. This real-time PCR
      assay demonstrated appropriate amplifications in all genotypes, and the results
      were consistent with those of conventional PCR. Second, the availability of
      Flinders Technology Associates filter paper (FTA card) as DNA templates for the
      real-time PCR assay was evaluated by using blood and saliva specimens to
      determine suitability for CEA screening. DNA-containing solution prepared from a
      disc of blood- or saliva-spotted FTA cards was available directly as templates
      for the real-time PCR assay when the volume of solution was 2.5% of the PCR
      mixture. In conclusion, SYBR Green-based real-time PCR combined with FTA cards is
      a rapid genotyping technique for CEA that can markedly shorten the overall time
      required for genotyping as well as simplify the sample preparation. Therefore,
      this newly developed technique suits large-scale screening in breeding
      populations of Collie-related breeds.

PMID- 20807926
TI  - The microanatomy of healthy skin from alpacas (Vicugna pacos).
AB  - The microanatomy of healthy skin from 12 different body sites was investigated in
      14 alpacas (Vicugna pacos). The microanatomy of alpaca skin is typical of
      domestic animal skin in general, and closely resembles that from llamas.

PMID- 20807927
TI  - The effect of inoculum volume on the microbiologic detection of naturally
      occurring Staphylococcus aureus intramammary infections.
AB  - Currently no standard definitions for the diagnosis of Staphylococcus aureus
      intramammary infection (IMI) exist. As a result, criteria applied in research to
      diagnose S. aureus IMIs have varied making comparisons between published works
      difficult. The goal of the current study was to define the optimal inoculum
      volume used in the diagnosis of naturally occurring S. aureus IMIs. Microbiologic
      results from 2 field studies examining S. aureus IMIs were used to examine the
      effects of inoculum volume on the microbiologic detection of S. aureus. A total
      of 1,583 milk samples were included in the analysis, and the results of using a
      0.01-ml and a 0.1-ml inoculum are presented. Using a 0.01-ml inoculum resulted in
      a sensitivity of 91% (95% confidence interval [CI]: 88.6-93%) and a specificity
      of 99.4% (95% CI: 98.6-99.8%). Using the larger 0.1-ml inoculum resulted in a
      sensitivity of 96.8% (95% CI: 95.2-97.9%) and a specificity of 99.3% (95% CI:
      98.4-99.7%). All false-positive samples were from S. aureus-negative quarters in
      S. aureus-positive cows. There were no false-positive cultures from S. aureus
      negative cows. Of the false-negative samples, the majority (77%) were from 6 of
      the 34 S. aureus-positive quarters. Results from the current study of naturally
      occurring S. aureus IMIs support the hypothesis that, when using quarter level
      milk samples, a S. aureus IMI is most accurately diagnosed using a 0.1-ml
      inoculum. Regardless of inoculum volume, a single quarter sample culture that is
      positive with S. aureus (>or=1 colony-forming unit) is sufficient to diagnose a
      S. aureus IMI.

PMID- 20807928
TI  - Comparison of three immunodiagnostic assays for antemortem detection of
      Mycobacterium bovis stimulation in domestic cats.
AB  - Mycobacterium bovis causes disease in numerous mammalian species including
      humans, thus making research, surveillance, and control important in the
      eradication of tuberculosis. Domestic cats are susceptible to multiple
      mycobacterial species including Mycobacterium bovis; however, their role in the
      epidemiology of bovine tuberculosis is not fully documented. The current study
      was an evaluation of the immune response in specific pathogen-free (SPF) cats
      stimulated with sensitinogen, a heat-killed M. bovis product, using the rapid
      test, multiple antigen print immunoassay (MAPIA), and bovine-purified protein
      derivative (bPPD) single skin test. Six cats were inoculated with sensitinogen
      subcutaneously on days 0 and 24; 2 noninoculated cats and 49 non-SPF cats were
      controls. Serial serum samples were collected during 135 days and assayed for M.
      bovis antibodies by rapid test and MAPIA. On day 123, bPPD skin test was
      performed and read at 48 and 72 hr. The bPPD test at 72 hr had a mean skin
      thickness of 0.3 mm for stimulated cats and 0.1 mm for controls. Rapid test
      identified 4 of 6 stimulated cats after bPPD injection. The MAPIA detected
      antibody against MPB83, 16/83, 16 kDa, and M. bovis culture filtrate (MBCF)
      antigens. All assays differentiated between stimulated and control cats; however,
      7 of 49 non-SPF control cats had a reaction for either antigen MBCF or 16/83.
      These preliminary studies show potential for antemortem detection of M. bovis
      among domestic cats. Additional studies to better characterize virulent M. bovis
      infection in cats would be of value.

PMID- 20807929
TI  - Comparison of two methods for blood lead analysis in cattle: graphite-furnace
      atomic absorption spectrometry and LeadCare(R) II system.
AB  - The current study compared the LeadCare(R) II test kit system with graphite
      furnace atomic absorption spectrometry for blood lead (Pb) analysis in 56 cattle
      accidentally exposed to Pb in the field. Blood Pb concentrations were determined
      by LeadCare II within 4 hr of collection and after 72 hr of refrigeration. Blood
      Pb concentrations were determined by atomic absorption spectrometry, and samples
      that were coagulated (n = 12) were homogenized before analysis. There was strong
      rank correlation (R(2) = 0.96) between atomic absorption and LeadCare II (within
      4 hr of collection), and a conversion formula was determined for values within
      the observed range (3-91 mcg/dl, although few had values >40 mcg/dl). Median and
      mean blood pb concentrations for atomic absorption were 7.7 and 15.9 mcg/dl,
      respectively; for LeadCare II, medians were 5.2 mcg/dl at 4 hr and 4.9 mcg/dl at
      72 hr, and means were 12.4 and 11.7, respectively. LeadCare II results at 4 hr
      strongly correlated with 72 hr results (R(2) = 0.96), but results at 72 hr were
      lower (P < 0.01). There was no significant difference between coagulated and
      uncoagulated samples run by atomic absorption. Although there have been several
      articles that compared LeadCare with other analytical techniques, all were for
      the original system, not LeadCare II. The present study indicated that LeadCare
      II results correlated well with atomic absorption over a wide range of blood Pb
      concentrations and that refrigerating samples for up to 72 hr before LeadCare II
      analysis was acceptable for clinical purposes.

PMID- 20807930
TI  - Growth rate retardation and inhibitory effect of para-JEM(R) BLUE on
      Mycobacterium avium subspecies paratuberculosis.
AB  - The effect of para-JEM(R) BLUE on Mycobacterium avium subspecies paratuberculosis
      (MAP) inoculated into broth-based culture media was evaluated by using 84 fecal
      samples with known MAP status. Results showed that growth of the organism in
      samples inoculated into the broth without the para-JEM BLUE was detectable 1-35
      days (average of 6 days) earlier in 35 of the samples (42%) compared with the
      same samples inoculated in broth with para-JEM BLUE. Four additional samples (5%)
      that were MAP positive in the culture broth that lacked the para-JEM BLUE gave
      negative results when the reagent was included. Of the remaining 45 samples,
      growth of MAP was detected 1-4 days (average of 3 days) earlier in 4 of the
      samples (5%) inoculated in the broth with para-JEM BLUE compared with the same
      samples inoculated in the broth without the para-JEM BLUE, whereas 41 samples
      (49%) yielded equivalent results with respect to time-to-growth detection and
      negative growth, regardless of whether para-JEM BLUE was present in the culture
      broth. However, exclusion of para-JEM BLUE from the broth increased the number of
      samples that produced false-positive instrument signals compared with the number
      that produced false-positive signals when the reagent was added. Modification of
      the sample processing step had no measurable effect. Observations indicated that,
      although elimination of para-JEM BLUE from the broth increased false-positive
      instrument signals, its inclusion has an adverse effect on the growth of certain
      MAP, which suggests that its elimination from broth cultures may increase
      sensitivity.

PMID- 20807931
TI  - Characterization of Canine parvovirus 2 variants circulating in Greece.
AB  - The aim of the present study was to characterize Canine parvovirus 2 (CPV-2)
      variants currently circulating in Greece. Between March 2008 and March 2009, 167
      fecal samples were collected from diarrheic dogs from different regions of
      Greece. Canine parvovirus 2 was detected by standard polymerase chain reaction,
      whereas minor groove binder probe assays were used to distinguish genetic
      variants and discriminate between vaccine and field strains. Of 84 CPV-2-positive
      samples, 81 CPV-2a, 1 CPV-2b, and 2 CPV-2c were detected. Vaccine strains were
      not detected in any sample. Sequence analysis of the VP2 gene of the 2 CPV-2c
      viruses revealed up to 100% amino acid identity with the CPV-2c strains
      previously detected in Europe. The results indicated that, unlike other European
      countries, CPV-2a remains the most common variant in Greece, and that the CPV-2c
      variant found in Europe is also present in Greece.

PMID- 20807932
TI  - Comparison of feces versus rectal swabs for the molecular detection of Lawsonia
      intracellularis in foals with equine proliferative enteropathy.
AB  - The purpose of the current study was to compare the molecular detection rate of
      Lawsonia intracellularis between feces and rectal swabs collected from 42 foals
      with suspected equine proliferative enteropathy (EPE). Fecal samples and rectal
      swabs were processed for DNA purification by using an automated extraction
      system. The purified DNA was then analyzed by real-time polymerase chain reaction
      (PCR) for the presence of the aspartate ammonia lyase (aspA) gene of L.
      intracellularis. Absolute quantitation was calculated by using a standard curve
      for L. intracellularis and expressed as copy numbers of the aspA gene of L.
      intracellularis per microliter of purified DNA. The combined PCR detection rate
      for L. intracellularis was 90%, with 38 foals testing PCR positive in feces (33
      samples), rectal swabs (32), or both (27). Six foals tested PCR positive only in
      feces, whereas 5 tested positive only in rectal swabs. Feces yielded a
      significantly higher aspA gene copy number of L. intracellularis than rectal
      swabs. Feces and rectal swabs tested PCR negative from 4 foals. In conclusion,
      the results showed that feces yielded similar numbers of PCR-positive results,
      with a higher L. intracellularis aspA gene load than rectal swabs. By analyzing
      dual samples, the PCR detection rate for L. intracellularis increased from 76%
      and 79% for rectal swabs and feces, respectively, to 90%. Rectal swabs should be
      considered as an alternative sample type for EPE-suspected patients with
      decreased or no fecal output.

PMID- 20807933
TI  - Border disease virus shedding and detection in naturally infected Pyrenean
      chamois (Rupicapra pyrenaica).
AB  - Pyrenean chamois (Rupicapra pyrenaica) populations of the central and eastern
      Pyrenees have been affected by severe outbreaks associated with Border disease
      virus (BDV) since 2001. Eight Pyrenean chamois (7 males and 1 female) from 1 to 8
      years of age with clinical signs consistent with BDV infection were studied. At
      necropsy, whole blood, tissue samples (skin, brain, prescapular lymph node,
      thyroid gland, lung, liver, spleen, kidney, small intestine, bone marrow, and
      testicle), urine, and nasal, oral, and rectal swabs were obtained. The fetus from
      a pregnant female was also studied. Reverse transcription polymerase chain
      reaction (RT-PCR) was used to detect the virus in all samples, and virus
      isolation was performed. Sera and tissue samples were positive to RT-PCR, and the
      virus was isolated from all chamois. The nasal, oral, and rectal swabs and urine
      samples were RT-PCR positive in 100%, 85.71%, 71.43%, and 100% of chamois,
      respectively, confirming the excretion of the virus via these 4 routes. In
      addition, sera were tested for BDV antibodies using enzyme-linked immunosorbent
      assay and seroneutralization techniques, with negative results. Sequence analysis
      of the 5' untranslated region in 7 of the chamois confirmed that the virus is
      grouped into the BDV-4 genotype, the same BDV previously described in Pyrenean
      chamois. To the authors' knowledge, this is the first study of naturally infected
      Pyrenean chamois, providing evidence that infected animals shed BDV through
      nasal, oral, fecal, and urinary excretion routes.

PMID- 20807934
TI  - Two new real-time quantitative reverse transcription polymerase chain reaction
      assays with unique target sites for the specific and sensitive detection of
      lineages 1 and 2 West Nile virus strains.
AB  - Two novel 1-step real-time quantitative reverse transcription polymerase chain
      reaction (qRT-PCR) assays for the simultaneous detection of West Nile virus (WNV)
      lineage 1 and 2 strains were developed. Primers and the probe of assay 1 target
      the 5'-untranslated region (UTR), whereas the amplicon of assay 2 is located in
      the nonstructural region NS2A, which enables an unambiguous and independent WNV
      diagnosis based on 2 different amplicons. Both assays allow the detection of as
      few as 2-4 genome copies of WNV strains NY99, Uganda B956, Kunjin, and Sarafend
      (all cultured on Vero cells). A new synthetic RNA mutant of the 5'-UTR amplicon,
      which contains 6 twist inverted base-pair changes at the probe attachment site,
      was used as external calibrator control.

PMID- 20807935
TI  - Ochratoxin A in serum of swine from different Brazilian states.
AB  - The aims of the current study were to monitor the presence of ochratoxin A (OTA)
      in the serum of slaughtered swine and to investigate its distribution in 4 major
      geographical regions of Brazil. A total of 400 samples of serum were collected
      from 4 major states of Brazil (100 samples each). Ochratoxin A concentrations
      were determined by high-performance liquid chromatography. In Santa Catarina
      State, 60% of the samples had OTA concentrations ranging from 4.01 to 75.4 mg/l.
      In Mato Grosso State, 75% of the samples had OTA concentrations ranging from 0.17
      to 46.79 mg/l. Bahia State samples had OTA concentrations ranging from 2.72 to
      4.13 mg/l in 36% of the samples, whereas 68% of the samples from Rio de Janeiro
      State had OTA concentrations ranging from 0.16 to 115 mg/l. Only Santa Catarina
      State and Rio de Janeiro State had serum samples that exceeded 75 mg/l OTA in 20%
      and 2% of the samples, respectively. A direct relationship between the higher
      concentrations of OTA in serum from the States of Santa Catarina and Rio de
      Janeiro and the highest concentrations of OTA in food intended for animal
      consumption in the same 2 Brazilian states was found in the present study.
      Ochratoxin A distribution in foodstuffs is very heterogeneous, and an alternative
      method by which to monitor the presence of OTA in feed includes analyzing swine
      serum samples, which reflect the toxin content of the ingested feed. This
      strategy could prevent the occurrence of ochratoxicosis in animal production,
      reduce economic losses, and minimize hazards to human health.

PMID- 20807936
TI  - Further diversity of the Staphylococcus intermedius group and heterogeneity in
      the MboI restriction site used for Staphylococcus pseudintermedius species
      identification.
AB  - Species identification of 200 beta-hemolysin-producing canine staphylococcal
      isolates was performed using a recently described polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) method (based on MboI
      restriction of a pta gene fragment), supplemented with biochemical testing and
      sequencing of housekeeping genes. The PCR-RFLP method misclassified a small
      fraction (approximately 1%) of the Staphylococcus pseudintermedius population as
      a result of heterogeneity in the MboI restriction site. A potentially novel
      species within the Staphylococcus intermedius group (SIG) was found, having
      closest similarity to S. intermedius based on sequence comparison to the genes
      sodA, pta, hsp60, tuf, and full-length 16S ribosomal DNA, thus demonstrating
      further species diversity within the SIG.

PMID- 20807937
TI  - Heteroduplex polymerase chain reaction is essential for canine receptor
      rearrangement analysis.
AB  - Polymerase chain reaction (PCR) for antigen receptor rearrangement is a sensitive
      technique for detecting lymphocyte-proliferative disorders, but it tends to
      produce false-positive results, a phenomenon termed pseudoclonality. Heteroduplex
      analysis, which is useful to distinguish clonal reactions from pseudoclonal ones
      in dogs, can be applied to avoid misdiagnosis and determine the reliability of
      results. In the current study, PCR for antigen receptor rearrangement was used to
      identify clonal proliferation of lymphocytes in duodenal and lymphoid tissue from
      dogs presenting with chronic vomiting and enlarged peripheral lymph nodes typical
      of multicentric lymphoma, and the test results were verified with heteroduplex
      analysis. In the case of almost all of the duodenal samples, even without a
      histologic diagnosis of lymphoma, a distinct band similar to that observed in the
      case of lymphoma was obtained for both B- and T-cell clonality. All of the bands
      obtained from the nonneoplastic duodenum disappeared following heteroduplex
      analysis of the PCR product, whereas the distinct bands from the lymphoma
      remained. In the lymph node samples, the pseudoclonal bands that disappeared in
      the heteroduplex analysis were detected mainly in B cells. In conclusion,
      heteroduplex analysis with PCR for antigen receptor rearrangement is a suitable
      tool for diagnosing canine lymphoma and decreasing the possibility of
      misdiagnosis of pseudoclonality.

PMID- 20807938
TI  - A survey of porcine picornaviruses and adenoviruses in fecal samples in Spain.
AB  - In the course of an epidemiologic surveillance program for swine diseases carried
      out in Spain, 206 cytopathic viruses were isolated from 600 porcine fecal samples
      between 2004 and 2005. The virus isolates were examined using reverse
      transcription polymerase chain reaction (RT-PCR) methods specific for different
      types of porcine picornaviruses, including members of the Teschovirus,
      Enterovirus, and Sapelovirus genera, and PCR for porcine adenoviruses. Of the 206
      isolates, 97 (47%) were identified as teschoviruses, 18 (9%) as sapeloviruses,
      and 7 (3%) as porcine adenoviruses. Neither Porcine enterovirus B nor Swine
      vesicular disease virus was found among the isolates. The present study confirms
      that teschoviruses are highly prevalent in porcine fecal samples, at least in
      Spain. It also reveals that these viruses commonly circulate among apparently
      healthy pigs.

PMID- 20807939
TI  - Prevalence of Mycoplasma haemolamae infection in Peruvian and Chilean llamas and
      alpacas.
AB  - Mycoplasma haemolamae is a hemotropic mycoplasma that affects red blood cells of
      llamas (Lama glama) and alpacas (Lama pacos). It is variably associated with
      anemia, and most infections are subclinical. Development of a polymerase chain
      reaction assay has facilitated detection of this infection in llamas and alpacas
      in the United States and other countries. Whether the infection occurs in
      camelids in South America has previously been unknown. The current study
      documents a 15.8% infection rate among 76 Peruvian llamas, a 19.3% infection rate
      among Peruvian alpacas at one site, and a 9.26% infection rate in 108 Chilean
      alpacas from selected herds. All of the camelids tested appeared to be clinically
      healthy. No gender or species predilection was found. Only 1 positive camelid
      younger than 18 months was found. Infection is not associated with anemia, and
      the mean packed cell volume (PCV) in positive Peruvian camelids was slightly
      higher than the mean PCV in negative Peruvian camelids. In the Chilean alpacas,
      the positive alpacas had a slightly lower PCV than the negative alpacas, although
      the mean PCV was not in the anemic range in any of the groups.

PMID- 20807940
TI  - Comparison of dog and rabbit plasmas in the tube coagulase test for
      Staphylococcus aureus.
AB  - The tube coagulase test, an invaluable laboratory tool for identifying
      Staphylococcus aureus, is most often done using rabbit plasma. However, there is
      evidence that depending on the origin of the isolates, other plasmas may be
      superior. The current study sought to compare the utility of dog and rabbit
      plasma in the coagulase test for S. aureus isolated from canine (n = 28), bovine
      (n = 29), and human (n = 30) hosts. Overall, coagulation times were significantly
      faster for dog (2.38 hr) than rabbit (3.19 hr) plasma. When coagulation times
      were compared by isolate origin, no significant differences were found for rabbit
      plasma, whereas bovine isolates clotted dog plasma significantly faster (1.86 hr)
      than canine (2.79 hr) or human (2.38 hr) isolates. Investigators should be aware
      that rabbit plasma may not be the ideal coagulase-testing medium for S. aureus
      from all sources.

PMID- 20807941
TI  - Stenotrophomonas maltophilia as a causal agent of pyogranulomatous hepatitis in a
      buffalo (Bubalus bubalis).
AB  - A 7-year-old female buffalo (Bubalus bubalis) from a local herd in Serres,
      northern Greece, was presented to a private veterinary clinic with a chronic loss
      of appetite for 15 days. The clinical examination revealed high fever (41.5
      degrees C), lethargy, yellow discoloration of skin and mucous membranes, an
      abdomen that appeared to be empty, hyperactive rumen motility, and tachypnea. A
      biochemical profile revealed an elevated total bilirubin concentration and
      hepatic enzyme activities, whereas globulin, creatinine, and glucose
      concentrations were within the reference intervals. The animal received a 12-day
      course of treatment with intramuscular administration of ampicillin and
      corticosteroids. However, no significant clinical improvement was achieved, and
      the buffalo was euthanized. Gross necropsy lesions included serous atrophy of
      adipose tissue and hepatomegaly. Microscopic lesions included necrotizing
      pyogranulomatous hepatitis with thrombosis, hemorrhages, edema, and fibrosis.
      Small, nonpigmented, bacterial colonies were harvested in pure culture from the
      liver and were confirmed as Stenotrophomonas maltophilia by polymerase chain
      reaction. The bacterium was sensitive to ciprofloxacin, enrofloxacin, colistin,
      polymyxin, trimethoprim/sulfamethaxazole, and chloramphenicol. In contrast,
      resistance to ticarcillin, piperacillin, imipenem, ceftazidime, amikacin,
      gentamicin, tobramycin, and tetracycline was displayed. The bacterial strain
      carried the L1 metallo-beta-lactamase (L1) and tet35 genes, which contribute to
      high-level resistance to beta-lactams and tetracycline, respectively. Although S.
      maltophilia is widely believed to be a contaminant, the present report suggests
      that the isolation, identification, and susceptibility testing of this multidrug
      resistant bacterium may be of clinical importance in diagnostic samples.

PMID- 20807942
TI  - Paraneoplastic hypercalcemia in a dog with benign renal angiomyxoma.
AB  - An 11-year-old, male, neutered crossbred Collie dog was presented for a history
      of polydipsia and polyuria. Diagnostic investigations revealed total and ionized
      hypercalcemia and an increased concentration of parathyroid hormone-related
      peptide. Abdominal ultrasonography and contrast-enhanced computed tomography of
      the abdomen revealed a right-sided, cystic-appearing renal mass. Cytological
      examination of ultrasound-guided aspirates of the mass revealed high numbers of
      spindle cells. The mass was removed en bloc via an ureteronephrectomy.
      Histopathological examination of the mass revealed neoplastic spindle cells in
      loosely packed and interlacing streams within a myxomatous stroma.
      Immunohistochemical examination with vimentin, von Willebrand Factor, and alpha
      smooth muscle actin confirmed the mass to be a renal angiomyxoma. A minority of
      the neoplastic spindle cells showed positive cytoplasmic parathyroid hormone
      related peptide immunostaining. The hypercalcemia resolved following surgery, and
      the parathyroid hormone-related peptide concentration returned to within the
      reference interval. The dog was no longer polydipsic or polyuric 1 year following
      surgery. The present report describes a previously unreported renal neoplasm
      causing paraneoplastic hypercalcemia and highlights the possibility of
      paraneoplastic hypercalcemia being caused by a benign neoplasm.

PMID- 20807943
TI  - Fatal canine adenoviral pneumonia in two litters of Bulldogs.
AB  - Five Bulldog pups, 4 weeks of age or younger, were presented over a 2-day period
      for postmortem examination and diagnostic evaluation. The pups originated from 2
      different litters but had been cared for at a common facility since their birth.
      All 5 pups died after exhibiting symptoms consisting of lethargy, dyspnea, nasal
      discharge, anorexia, vomiting, diarrhea, and abdominal pain. Necropsy examination
      revealed locally extensive to diffusely red, firm, consolidated lungs in all
      pups. Histopathologically, the lungs were variably effaced by multifocal areas of
      necrosis. The alveolar lumens contained fibrin, edema fluid, macrophages, and
      neutrophils. Many of the bronchioles contained cellular debris and neutrophils
      admixed with sloughed bronchiolar epithelium, which often contained large
      intranuclear amphophilic inclusion bodies that peripherally displaced chromatin.
      Fluorescent antibody testing was positive for Canine adenovirus. An adenovirus
      isolated via cell culture was positive on direct fluorescent antibody test and
      was identified as Canine adenovirus serotype 2 via polymerase chain reaction.
      Electron microscopy revealed typical viral inclusions within bronchiolar
      epithelial cells. Hemolytic Escherichia coli was also isolated from the lungs in
      3 of the 5 pups. The current case demonstrates a natural and rare fatal infection
      with a viral agent that is typically associated with immunosuppression in both
      animals and humans.

PMID- 20807944
TI  - Natural cases of 2009 pandemic H1N1 Influenza A virus in pet ferrets.
AB  - Respiratory swab samples were collected from 5 pet ferrets (Mustela putorius
      furo) exhibiting influenza-like illness. The ferrets represented 3 households in
      2 states. In each case, the owners reported influenza-like illness in themselves
      or family members prior to the onset of a similar illness in the ferrets. Real
      time reverse transcription polymerase chain reaction assays designed for the
      detection of the 2009 H1N1 Influenza A virus were conducted in the state animal
      health laboratories. The assays included detection of the matrix gene of
      Influenza A virus and neuraminidase gene specific for 2009 H1N1 virus. Samples
      were positive for both screening assays. The samples were confirmed positive by
      the National Veterinary Services Laboratories. The history of illness in family
      members prior to illness in the ferrets suggests that Influenza A virus was
      transmitted from humans to the ferrets.

PMID- 20807945
TI  - Atherosclerosis associated with pericardial effusion in a central bearded dragon
      (Pogona vitticeps).
AB  - Atherosclerosis is a common disease in pet birds, particularly in psittacines,
      and is frequently found when performing postmortem examinations on adult and old
      dogs, in which it is mainly associated with endocrine diseases, such as
      hypothyroidism and diabetes mellitus. However, atherosclerosis is poorly
      documented in reptiles and consequently poorly understood. In the current case
      report, atherosclerosis and pericardial effusion were diagnosed in a 2-year-old
      male central bearded dragon (Pogona vitticeps) based on ultrasound visualization,
      necropsy, and histologic examination.

PMID- 20807946
TI  - Focal symmetrical encephalomalacia in a goat.
AB  - Focal symmetrical encephalomalacia (FSE) is the most prominent lesion seen in the
      chronic form of enterotoxemia caused by Clostridium perfringens type D in sheep.
      However, this lesion has not been reported in goats. The current paper reports a
      case of FSE in a goat from the state of Paraiba in the Brazilian semiarid region.
      As reported by the farmer, 30, 4-48-month-old animals from a flock of 150 goats
      died after showing nervous signs, including blindness and recumbence, for periods
      varying between 1 and 14 days. The flock was grazing native pasture supplemented
      with wheat and corn bran. Additionally, lactating goats were supplemented with
      soybeans. A 4-month-old goat with nervous signs was examined clinically and then
      necropsied 3 days after the onset of clinical signs. Bilateral, focal, and
      symmetrical areas of brown discoloration were observed in the internal capsule
      and thalamus. Histologic lesions in these areas consisted of multifocal,
      bilateral malacia with a few neutrophils; endothelial cell swelling; perivascular
      edema; and hemorrhages. The etiology of these lesions was not determined.
      However, FSE is considered pathognomonic for C. perfringens type D enterotoxemia
      in sheep, and it is speculated that this microorganism was the etiologic agent in
      the present case. The flock had been vaccinated against type D enterotoxemia only
      once, approximately 3 months before the beginning of the outbreak. Insufficient
      immunity due to the incorrect vaccination protocol, low efficacy of the vaccine
      used, and a diet including large amounts of highly fermentable carbohydrates were
      suspected to be predisposing factors for this outbreak.

PMID- 20807948
TI  - Phalaris arundinacea (reed canarygrass) grass staggers in beef cattle.
AB  - Four adult mixed-breed beef cows from a cow-calf operation in West Virginia were
      referred to the Virginia-Maryland Regional College of Veterinary Medicine in
      March 2009 with weakness, ataxia, hind limb paresis progressing to lateral
      recumbency, and death within 2-3 days. Histologically, there was accumulation of
      light brown, granular pigment in neurons of the ventral gray horns of the spinal
      cord (more severe in thoracic and lumbar sections), brain stem, and pons,
      resulting in distortion and bulging of the cell body and displacement of the
      Nissl substance, suggestive of Phalaris sp. grass toxicosis. The most severely
      affected cow had accumulation of dark green-brown pigment in renal tubular
      epithelial cells. Reed canarygrass (Phalaris arundinacea) was identified in
      pastures, and the concentration of tryptamine alkaloids in new leaf blades was
      approximately 0.2% on a wet weight basis. These alkaloids are serotonergic
      receptor agonists, resulting in neurologic "staggers" in ruminants. Delayed onset
      times of up to 4-5 months have been reported in sheep after removal from Phalaris
      sp. pastures. Distribution of pigment in serotonergic tracts of the midbrain,
      brain stem, and spinal cord with Phalaris sp. toxicoses is distinct and differs
      from lipofuscin. Electron microscopy confirmed that the pigment was not
      lipofuscin. From these findings, a diagnosis of delayed P. arundinacea toxicosis
      was made. Over a 2-month period, 18 cows died with similar clinical signs.

PMID- 20807947
TI  - Mycoplasma bovis outbreak in a herd of North American bison (Bison bison).
AB  - A disease outbreak of high morbidity and high mortality in bison (Bison bison)
      was investigated. Clinical signs included lameness, swollen joints, respiratory
      distress, and lethargy. Fifty-three of 194 animals died. Cows between 5 and 10
      years of age were the most affected group, in which 40 of 88 animals died.
      Necropsies were performed on several animals. There were abscesses in the lung
      and liver, as well as fibrinosuppurative pleuritis, polyarthritis, and
      disseminated microabscesses in various organs. No significant bacteria were
      isolated by routine aerobic cultures of lung and liver from 2 representative
      cases. However, Mycoplasma cultures were positive. Polymerase chain reaction
      tests on the isolated bacteria were positive for Mycoplasma bovis.
      Histologically, the abscesses were characterized by areas of necrosis with
      variable mineralization rimmed by granulomatous inflammation and fibrous tissue.
      No new animals had been introduced into the herd, but a cattle herd was present
      adjacent to the affected bison herd. Two restriction fragment length polymorphism
      techniques were used to compare the bison isolate and another bison isolate from
      an outbreak in North Dakota with a field isolate of M. bovis from cattle and with
      a laboratory control strain of M. bovis; the isolates and control strain were
      found to be similar. The isolates and the control were sequenced and compared
      with sequences in GenBank. Bison isolates were more than 99% homologous to M.
      bovis sequences in GenBank. It was concluded that M. bovis in bison can cause
      disseminated infection with a high morbidity and mortality and that bison
      isolates are similar to bovine M. bovis isolates.

PMID- 20807949
TI  - Meningoencephalitis caused by Mycoplasma edwardii in a dog.
AB  - A 6-week-old, female, mixed-breed dog with a clinical history of sudden onset of
      neurologic signs was presented for necropsy. The dog was diagnosed with
      suppurative and histiocytic meningoencephalitis based on necropsy findings and
      histopathology. Mycoplasma sp. was isolated in pure culture from the brain and
      meninges and was identified as Mycoplasma edwardii using DNA sequencing.

PMID- 20807950
TI  - Mast cell tumors in a llama (Lama glama).
AB  - A 9-year-old female llama (Lama glama) that served as a blood donor at The Ohio
      State University Veterinary Teaching Hospital developed multiple small, raised,
      firm, non-haired cutaneous masses on the right hip, left cheek, and right and
      left shoulders. Cytological evaluation of fine-needle aspirates from the
      cutaneous mass from the left shoulder and right hip comprised many well
      differentiated, highly granulated mast cells with moderate numbers of
      eosinophils. Occasional mast cells exhibited erythrophagocytosis and contained a
      small amount of hemosiderin or several variably sized vacuoles. A cytologic
      diagnosis of mast cell tumor with evidence of prior hemorrhage was made, and the
      masses were surgically removed. Microscopically, each mass consisted of sheets of
      neoplastic round cells that formed nonencapsulated nodules in the dermis and
      infiltrated into the adjacent dermal collagen. Eosinophils were scattered among
      the mast cells at the periphery of the nodules. Neoplastic mast cells, but not
      eosinophils, exhibited positive membrane KIT expression and cytoplasmic vimentin
      staining. A final diagnosis of mast cell tumor was made based on cytology,
      histology, and immunohistochemistry.

PMID- 20807951
TI  - Juxtaductal coarctation of both pulmonary arteries in a cat.
AB  - A 4-year-old, male, neutered cat was referred because of recurrent episodes of
      dyspnea. Physical examination revealed a harsh systolic murmur, with the point of
      maximal intensity in the left heart base, with an intensity of 4 out of 6.
      Echocardiographic diagnosis was severe supravalvular pulmonary artery stenosis. A
      selective right ventricular angiocardiogram showed an absence of arterial blood
      flow to the left lung lobes. A balloon dilatation of the localized stenosis of
      the right pulmonary artery was attempted with cardiac catheterization. However,
      when the catheter was passed through the stenosis, the blood flow to the lungs
      temporarily completely ceased, which led to death. Postmortem examination
      revealed a circumscribed stenosis of both pulmonary arteries at the site of the
      bifurcation, where the ligamentum arteriosum was attached. Histopathology showed
      that the localized ridge-like stenosis at the pulmonary artery bifurcation was
      caused by connective tissue. The suspected cause of this congenital anomaly is
      the presence of ectopic ductal tissue in the wall of the pulmonary artery. When
      the ductus arteriosus closes at birth, pulmonary artery stenosis developed
      because of constriction of the ectopic ductal tissue.

PMID- 20807952
TI  - Focus issue: systems analysis of protein phosphorylation.
AB  - Kinases and phosphatases are key regulatory molecules that participate in most
      cell signaling pathways. Systems-level analyses are providing new insights into
      phosphorylation sites and kinase specificity, and phosphoproteomic analyses are
      creating not just a wealth of data, but are also revealing rich revelations about
      cellular behavior, cellular responses to changing environmental conditions, and
      mechanisms of disease. Phosphatases are not merely signal terminators, but play
      active roles in signal transduction and are especially important in redox
      signaling. In this Focus Issue, Science Signaling highlights protein
      phosphorylation as the center of the signaling universe.

PMID- 20807954
TI  - Comprehensive expression profiles of genes for protein tyrosine phosphatases in
      immune cells.
AB  - The phosphorylation and dephosphorylation of signaling molecules play a crucial
      role in various cellular processes, including immune responses. To date, the
      global expression profile of protein tyrosine phosphatases (PTPs) in various
      immune cells has not been described. With the RefDIC (Reference Genomics Database
      of Immune Cells) database compiled by RIKEN (Rikagaku Kenkyusho), we examined the
      expression patterns of PTP-encoding genes in mice and identified between 57 and
      64 PTP-encoding genes (depending on cutoff values) that were commonly expressed
      in immune cells. Cells of different lineages contained additional, unique PTP
      encoding genes, which resulted in a total of 58 to 76 genes. Compared with cells
      from nonimmune tissues, immune cells exhibited enhanced expression of the genes
      encoding 8 PTP-encoding genes, including Ptprc, Ptpn6, and Ptpn22, but had barely
      detectable expression of 11 PTP-encoding genes, including Ptprd and Tns1. Each
      immune cell lineage had between 2 and 18 PTP-encoding genes expressed at
      relatively high or low extents relative to the average expression among immune
      cells; for example, Ptprj in B cells, Dusp3 in macrophages, Ptpro in dendritic
      cells, and Ptprg in mast cells. These PTPs potentially play important roles in
      each cell lineage, and our analysis provides insight for future functional
      studies.

PMID- 20807953
TI  - Targeting the reversibly oxidized protein tyrosine phosphatase superfamily.
AB  - Controlled production of reactive oxygen species leads to reversible oxidation of
      protein tyrosine phosphatases (PTPs) and has emerged as an important tier of
      regulation over phosphorylation-dependent signal transduction. We present a
      modified cysteinyl-labeling assay that detects reversible oxidation of members of
      each of the different PTP subclasses. Here, we describe the methods for enriching
      reversibly oxidized PTPs from complex protein extracts, illustrating the
      procedure in IMR90 fibroblasts.

PMID- 20807955
TI  - Collection and motif-based prediction of phosphorylation sites in human viruses.
AB  - Although various databases have been established that are designed to compile an
      ever-growing list of protein phosphorylation sites in plants and animals, no such
      repository exists for viruses. Here, we developed the viral posttranslational
      modification (virPTM) database, which contains a comprehensive list of 329
      accurately localized phosphorylation sites in proteins from 52 human viruses
      published between 1986 and the present. Additionally, to aid in the detection of
      new viral phosphorylation sites, we used the scan-x tool to make thousands of
      high-specificity serine, threonine, and tyrosine phosphorylation predictions in
      229 viruses that replicate in human cells. By cross-validating our prediction
      results with the literature-based entries in the virPTM database, we highlight
      the effectiveness of the scan-x tool with viral data and extrapolate the
      existence of at least 4000 as yet unidentified phosphorylation sites on hundreds
      of viral proteins. Together, these results imply a substantial role for human
      kinases in mediating viral protein functions and suggest, more generally, that
      viral primary structure may provide important clues to aid in the rational design
      of therapeutic agents.

PMID- 20807956
TI  - Psychotic symptoms in the general population - an evolutionary perspective.
AB  - Our ideas about the intrinsically pathological nature of hallucinations and
      delusions are being challenged by findings from epidemiology, neuroimaging and
      clinical research. Population-based studies using both self-report and interview
      surveys show that the prevalence of psychotic symptoms is far greater than had
      been previously considered, prompting us to re-evaluate these psychotic symptoms
      and their meaning in an evolutionary context. This non-clinical phenotype may
      hold the key to understanding the persistence of psychosis in the population.
      From a neuroscientific point of view, detailed investigation of the non-clinical
      psychosis phenotype should provide novel leads for research into the aetiology,
      nosology and treatment of psychosis.

PMID- 20807958
TI  - Interpretation of interactions: guide for the perplexed.
AB  - In this issue, Zammit et al explore how five dichotomised risk factors work
      together to predict risk for non-affective psychosis in a large Swedish cohort.
      In this editorial, we review these findings, and comment on both the nature of
      additive v. multiplicative models and the meaning of statistical interactions.

PMID- 20807959
TI  - Culture and complex interventions: lessons for evidence, policy and practice.
AB  - Evidence-based mental healthcare is evolving rapidly. There is a need for well
      tested and effective interventions that are suited to culturally diverse
      populations. This editorial considers the findings from the SITARA study. There
      are a substantial number of implications for research, policy and practice.

PMID- 20807960
TI  - Efficacy of antidepressants in treating the negative symptoms of chronic
      schizophrenia: meta-analysis.
AB  - BACKGROUND: Treatment of negative symptoms in chronic schizophrenia continues to
      be a major clinical issue. AIMS: To analyse the efficacy of add-on
      antidepressants for the treatment of negative symptoms of chronic schizophrenia.
      METHOD: Systematic review and meta-analysis of randomised controlled trials
      comparing the effect of antidepressants and placebo on the negative symptoms of
      chronic schizophrenia, measured through standardised rating scales. Outcome was
      measured as standardised mean difference between end-of-trial and baseline scores
      of negative symptoms. RESULTS: There were 23 trials from 22 publications (n =
      819). The antidepressants involved were selective serotonin reuptake inhibitors,
      mirtazapine, reboxetine, mianserin, trazodone and ritanserin; trials on other
      antidepressants were not available. The overall standardised mean difference was
      moderate (-0.48) in favour of antidepressants and subgroup analysis revealed
      significant responses for fluoxetine, trazodone and ritanserin. CONCLUSIONS:
      Antidepressants along with antipsychotics are more effective in treating the
      negative symptoms of schizophrenia than antipsychotics alone.

PMID- 20807961
TI  - Parental history of depression or anxiety and the cortisol awakening response.
AB  - BACKGROUND: It is unclear whether altered hypothalamic-pituitary-adrenal (HPA)
      axis regulation, which frequently accompanies depression and anxiety disorders,
      represents a trait rather than a state factor. AIMS: To examine whether HPA axis
      dysregulation represents a biological vulnerability for these disorders, we
      compared cortisol levels in unaffected people with and without a parental history
      of depressive or anxiety disorders. We additionally examined whether possible HPA
      axis dysregulations resemble those observed in participants with depression or
      anxiety disorders. METHOD: Data were from the Netherlands Study of Depression and
      Anxiety. Within the participants without a lifetime diagnoses of depression or
      anxiety disorders, three groups were distinguished: 180 people without parental
      history, 114 with self-reported parental history and 74 with CIDI-diagnosed
      parental history. These groups were additionally compared with people with major
      depressive disorder or panic disorder with agoraphobia (n = 1262). Salivary
      cortisol samples were obtained upon awakening, and 30, 45 and 60 min later.
      RESULTS: As compared with unaffected participants without parental history,
      unaffected individuals with diagnosed parental history of depression or anxiety
      showed a significantly higher cortisol awakening curve (effect size (d) = 0.50),
      which was similar to that observed in the participants with depression or anxiety
      disorders. Unaffected people with self-reported parental history did not differ
      in awakening cortisol levels from unaffected people without parental history.
      CONCLUSIONS: Unaffected individuals with parental history of depression or
      anxiety showed a higher cortisol awakening curve, similar to that of the
      participants with depression or anxiety disorders. This suggests that a higher
      cortisol awakening curve reflects a trait marker, indicating an underlying
      biological vulnerability for the development of depressive and anxiety disorders.

PMID- 20807962
TI  - Neurodevelopmental marker for limbic maldevelopment in antisocial personality
      disorder and psychopathy.
AB  - BACKGROUND: Antisocial personality disorder and psychopathy have been
      hypothesised to have a neurodevelopmental basis, but this proposition has not
      been formally tested. AIMS: This study tests the hypothesis that individuals with
      cavum septum pellucidum (CSP), a marker of limbic neural maldevelopment, will
      show higher levels of psychopathy and antisocial personality. METHOD: Cavum
      septum pellucidum was assessed using anatomical magnetic resonance imaging in a
      community sample. Those with CSP (n = 19) were compared with those lacking CSP (n
      = 68) on antisocial personality, psychopathy and criminal offending. RESULTS:
      Those with CSP had significantly higher levels of antisocial personality,
      psychopathy, arrests and convictions compared with controls. The pervasiveness of
      this association was indicated by the fact that those lacking a diagnosis of
      antisocial personality disorder, but who were charged or convicted for an
      offence, had a more extensive CSP than non-antisocial controls. Results could not
      be attributed to prior trauma exposure, head injury, demographic factors or
      comorbid psychiatric conditions. CONCLUSIONS: Our findings appear to be the first
      to provide evidence for a neurodevelopmental brain abnormality in those with
      antisocial personality disorder and psychopathy, and support the hypothesis that
      early maldevelopment of limbic and septal structures predisposes to the spectrum
      of antisocial behaviours.

PMID- 20807963
TI  - Personality pathology recorded by severity: national survey.
AB  - BACKGROUND: Current classifications of personality disorders do not classify
      severity despite clinical practice favouring such descriptions. AIMS: To assess
      whether an existing measure of severity of personality disorder predicted
      clinical pathology and societal dysfunction in a community sample. METHOD: UK
      national epidemiological study in which personality status was measured using the
      screening version of the Structured Clinical Interview for DSM-IV Personality
      Disorders (SCID-II) and reclassified to five levels using a modified severity
      index. Associations between levels of severity of personality pathology and
      social, demographic and clinical variables were measured. RESULTS: Of 8391
      individuals interviewed and their personality status assessed, only a minority (n
      = 1933, 23%) had no personality pathology. The results supported the hypothesis.
      More severe personality pathology was associated incrementally with younger age,
      childhood institutional care, expulsion from school, contacts with the criminal
      justice system, economic inactivity, more Axis I pathology and greater service
      contact (primary care and secondary care, all P<0.001). Significant handicap was
      noted among people with even low levels of personality pathology. No differences
      contradicted the main hypothesis. CONCLUSIONS: A simple reconstruction of the
      existing classification of personality disorder is a good predictor of social
      dysfunction and supports the development of severity measures as a critical
      requirement in both DSM-V and ICD-11 classifications.

PMID- 20807964
TI  - Alcohol-induced psychotic disorder and delirium in the general population.
AB  - BACKGROUND: Epidemiological data on alcohol-induced psychotic disorder and
      delirium (alcohol-induced psychotic syndrome, AIPS) are scarce. AIMS: To
      investigate the epidemiology of AIPS, the risk factors for developing AIPS among
      people with alcohol dependence, and mortality associated with alcohol dependence
      with or without AIPS, in a sample drawn from the general population of Finland.
      METHOD: A general population sample of 8028 persons were interviewed with the
      Composite International Diagnostic Interview and screened for psychotic disorders
      using multiple sources. Best-estimate diagnoses of psychotic disorders were made
      using the Structured Clinical Interview for DSM-IV Axis I Disorders and case
      notes. Data on hospital reatments and deaths were collected from national
      registers. RESULTS: The lifetime prevalence was 0.5% for AIPS and was highest
      (1.8%) among men of working age. Younger age at onset of alcohol dependence, low
      socioeconomic status, father's mental health or alcohol problems and multiple
      hospital treatments were associated with increased risk of AIPS. Participants
      with a history of AIPS had considerable medical comorbidity, and 37% of them died
      during the 8-year follow-up. CONCLUSIONS: Alcohol-induced psychotic disorder is a
      severe mental disorder with poor outcome.

PMID- 20807965
TI  - Examining interactions between risk factors for psychosis.
AB  - BACKGROUND: For complex multifactorial diseases it seems likely that co-exposure
      to two risk factors will show a greater than additive relationship on disease
      risk. AIMS: To test whether greater than additive relationships occur between
      risk factors for psychosis. METHOD: A cohort study of 50 053 Swedish conscripts.
      Data on IQ, cannabis use, psychiatric diagnoses, disturbed behaviour and social
      relations assessed at age 18 were linked to admissions with any non-affective
      psychoses over a 27-year follow-up period. Statistical interactions between risk
      factors were examined under both additive and multiplicative models. RESULTS:
      There was some evidence of interaction for eight of the ten combinations of risk
      factors under additive models, but for only one combination under multiplicative
      models. CONCLUSIONS: Multiplicative models describe the joint effect of risk
      factors more adequately than additive ones do. However, the implications of
      finding interactions as observed here, or for most interactions reported to date,
      remain very limited.

PMID- 20807966
TI  - Ethnic differences in self-harm, rates, characteristics and service provision:
      three-city cohort study.
AB  - BACKGROUND: Studies of self-harm in Black and minority ethnic (BME) groups have
      been restricted to single geographical areas, with few studies of Black people.
      AIMS: To calculate age- and gender-specific rates of self-harm by ethnic group in
      three cities and compare characteristics and outcomes. METHOD: A population-based
      self-harm cohort presenting to five emergency departments in three English cities
      during 2001 to 2006. RESULTS: A total of 20 574 individuals (16-64 years)
      presented with self-harm; ethnicity data were available for 75%. Rates of self
      harm were highest in young Black females (16-34 years) in all three cities. Risk
      of self-harm in young South Asian people varied between cities. Black and
      minority ethnic groups were less likely to receive a psychiatric assessment and
      to re-present with self-harm. CONCLUSIONS: Despite the increased risk of self
      harm in young Black females fewer receive psychiatric care. Our findings have
      implications for assessment and appropriate management for some BME groups
      following self-harm.

PMID- 20807968
TI  - Psychiatric disorders in women prisoners who have engaged in near-lethal self
      harm: case-control study.
AB  - BACKGROUND: Female prisoners are 20 times more likely to die by suicide than
      women of the same age in the general population. However, risk factors and
      indicators of vulnerability for suicide in this group are not well-known. AIMS:
      We investigated prevalence of psychiatric disorders in women prisoners who had
      recently engaged in near-lethal self-harm (cases) and others who had never
      carried out near-lethal attempts in prison (controls). METHOD: We interviewed 60
      cases and 60 controls from all closed female prison establishments in England and
      Wales. In addition to gathering details of sociodemographic, criminological and
      clinical history, we assessed participants' current and lifetime disorders using
      the Mini-International Neuropsychiatric Interview. Associations between near
      lethal self-harm and psychiatric disorders were adjusted for age, educational
      qualifications (any v. none) and remand status (sentenced v. unsentenced).
      RESULTS: At the time of their near-lethal self-harm, 53 cases (88%) were on ACCT
      (Assessment, Care in Custody and Teamwork), the system for the care of prisoners
      at risk of suicide and self-harm in England and Wales. Cases had significantly
      greater levels of psychiatric morbidity than controls, and more comorbidity. The
      strongest associations with near-lethal self-harm were with current depression
      (age-adjusted odds ratio (OR) = 23.7, 95% CI 9.0-62.3), the presence of two or
      more diagnoses (age-adjusted OR = 18.3, 95% CI 5.9-56.9), a history of
      psychiatric in-patient treatment (OR = 25.4, 95% CI 5.7-113.5) and previous
      attempted suicide, especially in prison (OR = 129, 95% CI 27-611). The only
      tested diagnoses not associated with near-lethal self-harm were antisocial
      personality disorder, substance use and eating disorders. Adjusting for
      sociodemographic and criminological variables did not significantly alter any of
      these findings. CONCLUSIONS: This research underlines the importance of
      psychiatric risk factors for suicide in custody and in particular comorbidity.
      The finding that a formal care plan was in place for most cases at the time of
      their near-lethal act is indicative of good risk detection, but also suggests
      high levels of unmet need. Given the potential complexity of their mental health
      needs, interventions incorporating pharmacological and psychological treatments
      should be considered for at-risk prisoners.

PMID- 20807969
TI  - Social intervention for British Pakistani women with depression: randomised
      controlled trial.
AB  - BACKGROUND: British Pakistani women have a high prevalence of depression. There
      are no reported psychosocial interventions for depression in ethnic minorities in
      the UK. AIMS: To determine the efficacy of a social group intervention compared
      with antidepressants, and whether the combination of the two is more efficacious
      than either alone. METHOD: A total of 123 women with depression participated in
      the primary care-based cluster randomised controlled trial (ISRCTN19172148).
      Outcome measures were severity of depression (Hamilton Rating Scale for
      Depression), social functioning and satisfaction at 3 and 9 months. RESULTS:
      Greater improvement in depression in the social intervention group and the
      combined treatment group compared with those receiving antidepressants alone fell
      short of significance. There was significantly greater improvement in social
      functioning in the social intervention and combined treatment groups than in the
      antidepressant group at both 3 and 9 months. CONCLUSIONS: Pakistani women with
      depression found the social groups acceptable and their social function and
      satisfaction improved if they received social treatment compared with the receipt
      of antidepressants alone.

PMID- 20807970
TI  - Role of media reports in completed and prevented suicide: Werther v. Papageno
      effects.
AB  - BACKGROUND: Media reporting of suicide has repeatedly been shown to trigger
      suicidal behaviour. Few studies have investigated the associations between
      specific media content and suicide rates. Even less is known about the possible
      preventive effects of suicide-related media content. AIMS: To test the hypotheses
      that certain media content is associated with an increase in suicide, suggesting
      a so-called Werther effect, and that other content is associated with a decrease
      in suicide, conceptualised as a Papageno effect. Further, to identify classes of
      media articles with similar reporting profiles and to test for associations
      between these classes and suicide. METHOD: Content analysis and latent class
      analysis (LCA) of 497 suicide-related print media reports published in Austria
      between 1 January and 30 June 2005. Ecological study to identify associations
      between media item content and short-term changes in suicide rates. RESULTS:
      Repetitive reporting of the same suicide and the reporting of suicide myths were
      positively associated with suicide rates. Coverage of individual suicidal
      ideation not accompanied by suicidal behaviour was negatively associated with
      suicide rates. The LCA yielded four classes of media reports, of which the
      mastery of crisis class (articles on individuals who adopted coping strategies
      other than suicidal behaviour in adverse circumstances) was negatively associated
      with suicide, whereas the expert opinion class and the epidemiological facts
      class were positively associated with suicide. CONCLUSIONS: The impact of suicide
      reporting may not be restricted to harmful effects; rather, coverage of positive
      coping in adverse circumstances, as covered in media items about suicidal
      ideation, may have protective effects.

PMID- 20807971
TI  - Pernicious anaemia presenting as catatonia without signs of anaemia or
      macrocytosis.
AB  - Pernicious anaemia can present with psychiatric symptoms before haematological or
      neurological manifestations appear. We describe a young woman who presented with
      insidious onset catatonia without evidence of psychosis or depression. Blood
      count and mean cell volume were normal and neurological findings were equivocal.
      Low B(12) levels and intrinsic factor antibodies were found only by chance when
      they were included in a battery of further investigations. B(12) replacement was
      followed by prompt improvement. This case provides an argument for wider
      screening for B(12) deficiency in certain individuals with psychiatric disorders.

PMID- 20807972
TI  - Group-based psychosocial intervention for bipolar disorder.

PMID- 20807974
TI  - Effects of befriending on depressive symptoms: a precautionary note on promising
      findings.

PMID- 20807976
TI  - Chronic kidney disease and postoperative morbidity after elective orthopedic
      surgery.
AB  - BACKGROUND: Reduced estimated glomerular filtration rate (eGFR) is strongly
      associated with increased cardiovascular risk and all-cause mortality.
      Associations with morbidity in elective, moderate-risk noncardiac surgery have
      not been explored. We hypothesized that chronic kidney disease (CKD) would be
      associated with excess morbidity after elective, moderate-risk orthopedic
      surgery. METHODS: Patients undergoing elective orthopedic joint replacement
      procedures were studied, representing a large proportion of global surgical
      procedures and characterized by highly homogeneous anesthetic and surgical
      practice. eGFR was calculated from routine creatinine measurements using the
      Modification of Diet in Renal Disease equation. CKD was defined as eGFR < 60
      mL/min/1.73 m2. Cardiac risk (Revised Cardiac Risk Index) and evidence-based,
      perioperative factors associated with perioperative morbidity (operative time,
      blood loss, perioperative temperature) were also recorded prospectively. The
      primary end point was postoperative morbidity, recorded prospectively using the
      postoperative morbidity survey. Morbidity differences were analyzed between
      patients with CKD and normal preoperative renal function (chi2 test for trend)
      and presented as hazard ratio (HR) or odds ratio (OR) with 95% confidence
      intervals (95% CIs). The secondary end points were time to hospital discharge and
      time to become morbidity free (analyzed by log-rank test), both between and
      within CKD compared with normal renal function patients. Multiple regression
      analysis was performed to assess the association of CKD, perioperative factors
      with morbidity, and length of hospital stay. RESULTS: Postoperative morbidity
      survey was recorded in 526 patients undergoing elective orthopedic surgery. CKD
      patients (n = 142; 27%) sustained excess morbidity on postoperative day 5 (OR 2.1
      [95% CI: 1.2-3.7]; P < 0.0001). CKD patients took longer (HR 1.6 [95% CI: 1.2
      1.9]) to become morbidity free (log-rank test, P < 0.0001). Time to hospital
      discharge was delayed by 4 days in CKD patients (HR 1.4 [95% CI: 1.2-1.7]; P =
      0.0001; log-rank test). CKD patients sustained more pulmonary (OR 2.2 [95% CI:1.3
      3.6]; P = 0.002), infectious (OR 1.7 [95% CI:1.1-2.7]; P = 0.01), cardiovascular
      (OR 2.4 [95% CI: 1.2-4.8]; P = 0.01), renal (OR 2.3 [95% CI:1.5-3.5]; P <
      0.00,001), neurological (OR 4.3 [95% CI:1.3-17.7]; P = 0.005), and pain (OR 1.8
      [95% CI:1.03-3.1]; P = 0.04) morbidities. Further stratification of CKD revealed
      preoperative eGFR <= 50 mL/min/1.73 m(2) to be associated with more frequent
      morbidity and longer hospital stay, independent of age. Multiple regression
      analysis identified CKD (P = 0.006) and congestive cardiac failure (P = 0.002) as
      preoperative factors associated with prolonged hospital stay. CONCLUSIONS: A
      substantial minority of patients with CKD undergoing elective orthopedic
      procedures are at increased risk of prolonged morbidity and hospital stay.
      Preoperative eGFR may enhance perioperative risk stratification beyond
      traditional risk factors.

PMID- 20807977
TI  - Successful treatment with low-dose imatinib mesylate of therapy-related myeloid
      neoplasm harboring TEL-PDGFRB in a patient with acute promyelocytic leukemia.

PMID- 20807978
TI  - Is stem cell transplantation the treatment of choice in pediatric chronic myeloid
      leukemia?

PMID- 20807979
TI  - Clinical characteristics and treatment outcome of pediatric patients with chronic
      myeloid leukemia.

PMID- 20807980
TI  - Modeling the marrow stem cell niche in vitro: is proximity the key to
      reproduction?

PMID- 20807981
TI  - Bleeding symptoms in heterozygous factor XIII [corrected] deficiency.

PMID- 20807982
TI  - Regulating traffic in the hematopoietic stem cell niche.

PMID- 20807983
TI  - Biological diversity and risk-adapted treatment of chronic lymphocytic leukemia.

PMID- 20807984
TI  - Pathogenesis and treatment of acquired idiopathic thrombotic thrombocytopenic
      purpura.

PMID- 20807985
TI  - Biological individuality and the new frontiers of immunological tolerance in
      hematopoietic stem cell transplantation.

PMID- 20807986
TI  - JRSM and society meetings.

PMID- 20807987
TI  - Networking for healthcare reform.

PMID- 20807988
TI  - E-learning course.

PMID- 20807989
TI  - Whither the journal?

PMID- 20807990
TI  - 'Too high a percentage of failures'? Cover-up at the New Hospital for Women.

PMID- 20807991
TI  - Beyond statin therapy: a review of the management of residual risk in diabetes
      mellitus.
AB  - Total cholesterol and low-density lipoprotein (LDL) cholesterol exhibit an
      independent, strong, continuous correlation with cardiovascular events. The
      effectiveness of hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
      (statins) in the treatment and prevention of atherosclerosis is well-established.
      However, despite the lowering of LDL targets and the increased use of statins,
      patients with type 2 diabetes mellitus (DM) continue to experience a higher
      proportion of adverse coronary artery disease events. This is as a result of an
      atherogenic dyslipidaemia, characterized by low levels of high-density
      lipoprotein and elevated plasma triglyceride concentrations, often with high
      levels of cholesterol-rich remnant particles. This article will review
      dyslipidaemia and its role in DM, and will discuss available treatment modalities
      that address residual cardiovascular risk in this disease.

PMID- 20807992
TI  - Delivering regional thrombolysis via a hub-and-spoke model.
AB  - OBJECTIVES: Audits in the United Kingdom and other countries show that only a
      small proportion of eligible stroke patients receive thrombolysis. Providing 24
      hour thrombolysis cover presents major challenges in both infrastructure and
      staffing. One model for improving access is to provide out-of-hours cover in a
      regional centre but this may present problems including greater delays to
      hospital admissions. DESIGN: Evaluation of the introduction of a 'hub-and-spoke'
      model of thrombolysis to increase access to thrombolysis for patients in south
      west London. One-year data are presented. SETTING: A network in south-west London
      comprised of a hub hospital and three district 'spoke' hospitals. PARTICIPANTS:
      All suspected stroke admissions to a regional stroke centre. Main outcome
      measures Thrombolysis rates for acute stroke. RESULTS: Increased out-of-hours
      thrombolysis rates were achieved with only a small increase in stroke admissions
      (approximately 10%) in the hub hospital. Thrombolysis rates increased from 1.2
      per 100 stroke admissions for the local daytime service to 6 per 100 admissions
      for the regional service. Most patients thrombolysed were not local to the hub
      hospital. Only 1 in 4 patients considered for thrombolysis was thrombolysed, in
      line with previous data. Ten percent of all thrombolysis calls were not stroke
      but represented stroke mimics. Median length of stay was 6 days (target was 3
      days). Fifty percent of the thrombolysed patients from spoke hospitals were
      discharged directly home. CONCLUSIONS: In an urban area, a hub-and-spoke
      thrombolysis model increased access to thrombolysis without resulting in a marked
      increase in overall stroke admission numbers for the hub hospital. Proactive
      plans to repatriate patients back to district hospitals are required, and
      repatriation protocols have to prioritize regional patients over other targets in
      spoke hospitals to facilitate capacity in the hub hospital.

PMID- 20807993
TI  - External aortic root support for Marfan syndrome: early clinical results in the
      first 20 recipients with a bespoke implant.
AB  - OBJECTIVES: Fatal aortic dissection occurs at young age in Marfan syndrome.
      Prevention relies on elective replacement of the aortic root. The placement of an
      external aortic root support, tailored to the anatomy of the individual patient
      has been proposed as a feasible alternative. DESIGN, SETTING AND MAIN OUTCOME
      MEASURES: External aortic root support was offered to patients with Marfan
      syndrome with aortic root diameter of 40-55 mm and without aortic regurgitation.
      By computer-aided design, a model of the individual patient's aorta was created
      from cardiac magnetic resonance images and a bespoke external aortic support was
      manufactured. Comparative measurements were made of the ascending aorta at the
      level of closure of the aortic valve cusps from magnetic resonance imaging
      studies taken preoperatively, at first follow-up, and at most recent follow-up.
      For patients having aortic root surgery at the same institution, in the same time
      frame as the first 10 patients, clinical data were retrieved on Marfan and other
      patients having aortic root replacement to serve as a reference data. RESULTS:
      Twenty patients were operated upon from May 2004 to October 2009, 13 men and 7
      women, median age 33 years. All 20 patients are alive and well at the time of
      last follow-up. Preoperative aortic diameters were 40-54 mm. All postoperative
      images were satisfactory with an overall reduction in aortic root dimensions. The
      surgery took half the time of other aortic root surgery. Cardiopulmonary bypass
      was used only in the first patient, myocardial ischemia was not required in any
      patient, and no postoperative anticoagulation is mandated. CONCLUSIONS: The
      primary objective of this surgery was fully achieved in 19 of the 20 patients,
      reinforcing the ascending aorta while leaving the native aortic valve intact and
      conserving the blood/endothelium interface.

PMID- 20807994
TI  - Is all that fluctuates delirium?

PMID- 20807995
TI  - An early 18th-century proposal for improving medicine by tabulating and analysing
      practice.

PMID- 20807996
TI  - Edmund Hey - a personal appreciation.

PMID- 20807997
TI  - The autophagic degradation of chloroplasts via rubisco-containing bodies is
      specifically linked to leaf carbon status but not nitrogen status in Arabidopsis.
AB  - Autophagy is an intracellular process facilitating the vacuolar degradation of
      cytoplasmic components and is important for nutrient recycling during starvation.
      We previously demonstrated that chloroplasts can be partially mobilized to the
      vacuole by autophagy via spherical bodies named Rubisco-containing bodies (RCBs).
      Although chloroplasts contain approximately 80% of total leaf nitrogen and
      represent a major carbon and nitrogen source for new growth, the relationship
      between leaf nutrient status and RCB production remains unclear. We examined the
      effects of nutrient factors on the appearance of RCBs in leaves of transgenic
      Arabidopsis (Arabidopsis thaliana) expressing stroma-targeted fluorescent
      proteins. In excised leaves, the appearance of RCBs was suppressed by the
      presence of metabolic sugars, which were added externally or were produced during
      photosynthesis in the light. The light-mediated suppression was relieved by the
      inhibition of photosynthesis. During a diurnal cycle, RCB production was
      suppressed in leaves excised at the end of the day with high starch content.
      Starchless mutants phosphoglucomutase and ADP-Glc pyrophosphorylase1 produced a
      large number of RCBs, while starch-excess mutants starch-excess1 and maltose
      excess1 produced fewer RCBs. In nitrogen-limited plants, as leaf carbohydrates
      were accumulated, RCB production was suppressed. We propose that there exists a
      close relationship between the degradation of chloroplast proteins via RCBs and
      leaf carbon but not nitrogen status in autophagy. We also found that the
      appearance of non-RCB-type autophagic bodies was not suppressed in the light and
      somewhat responded to nitrogen in excised leaves, unlike RCBs. These results
      imply that the degradation of chloroplast proteins via RCBs is specifically
      controlled in autophagy.

PMID- 20807998
TI  - Identification of a novel abscisic acid-regulated farnesol dehydrogenase from
      Arabidopsis.
AB  - In Arabidopsis (Arabidopsis thaliana), farnesylcysteine is oxidized to farnesal
      and cysteine by a membrane-associated thioether oxidase called farnesylcysteine
      lyase. Farnesol and farnesyl phosphate kinases have also been reported in plant
      membranes. Together, these observations suggest the existence of enzymes that
      catalyze the interconversion of farnesal and farnesol. In this report,
      Arabidopsis membranes are shown to possess farnesol dehydrogenase activity. In
      addition, a gene on chromosome 4 of the Arabidopsis genome (At4g33360), called
      FLDH, is shown to encode an NAD(+)-dependent dehydrogenase that oxidizes farnesol
      more efficiently than other prenyl alcohol substrates. FLDH expression is
      repressed by abscisic acid (ABA) but is increased in mutants with T-DNA
      insertions in the FLDH 5' flanking region. These T-DNA insertion mutants, called
      fldh-1 and fldh-2, are associated with an ABA-insensitive phenotype, suggesting
      that FLDH is a negative regulator of ABA signaling.

PMID- 20808001
TI  - Effect of cage geometry on sagittal alignment after posterior lumbar interbody
      fusion for degenerative disc disease.
AB  - PURPOSE: To compare the sagittal alignment of the lumbar spine after one-segment
      posterior lumbar interbody fusion (PLIF) using the horizontal cylinder (HC) or
      open box (OB) type cage. METHODS: 66 patients underwent instrumented one-segment
      PLIF with bone grafting for lower lumbar degenerative disease. HC-type cages were
      used in 33 men and 13 women aged 20 to 73 (mean, 47) years between September 2001
      and July 2004. OB-type cages with a 3-degree lordotic angle were used in 9 men
      and 11 women aged 25 to 70 (mean, 53) years between July 2004 and September 2006.
      Pre- and post-operative lumbar lordosis and intervertebral body angles in the
      fused and upper adjacent levels in the 2 groups were compared. RESULTS: There was
      no significant difference between the 2 groups with regard to changes in the
      lumbar lordosis and intervertebral body angle in the fused and upper adjacent
      levels. In both groups, the upper adjacent intervertebral body angle increased
      significantly by about 2 degrees. CONCLUSION: Lumbar alignment was similar after
      the use of the HC- or OB-type cages. This may be due to the surgical procedure
      and insufficient cage lordotic angle.

PMID- 20808000
TI  - A multidisciplinary rehabilitation programme for patients with chronic low back
      pain: a prospective study.
AB  - PURPOSE: To examine the effectiveness of a multidisciplinary rehabilitation
      programme for patients with chronic low back pain in Hong Kong, and to identify
      factors associated with work resumption. METHODS: 57 men and 8 women aged 20 to
      56 (mean, 39) years who had a more than 3-month history of low back pain and were
      unresponsive to more than 6 months of conventional treatment participated in a 14
      week multidisciplinary rehabilitation programme involving physical conditioning,
      work conditioning, and work readiness. Training protocols entailed flexibility
      and endurance training, hydrotherapy, weight lifting, and work stimulation.
      Patients were assessed at baseline (week 1), week 7, week 14, and month 6 with
      regard to the intensity of low back pain, self-perceived disability, range of
      lumbar motion, isoinertial performance of the trunk muscles, and depression
      level. Patient demographics that influenced work resumption were identified using
      a prediction model. Patients who did and did not return to work were compared.
      RESULTS: Of the 54 patients who completed all follow-up assessments, 28 returned
      to work and 26 did not. The latter was significantly older (37 vs. 42 years,
      p=0.038) and absent from work longer (11 vs. 22 months, p=0.029) than the former.
      The rehabilitation programme helped patients regain physical function and the
      ability to work. Patients who returned to work showed greater improvement in self
      perceived disability and physical function. CONCLUSION: This rehabilitation
      programme facilitated regain of physical functioning and the ability to return to
      work. The pre-programme employment status, duration of absence from work, and
      patient age were the most important predictors for work resumption.

PMID- 20807999
TI  - Molecular and physiological analysis of drought stress in Arabidopsis reveals
      early responses leading to acclimation in plant growth.
AB  - Plant drought stress response and resistance are complex biological processes
      that need to be analyzed at a systems level using genomics and physiological
      approaches to dissect experimental models that address drought stresses
      encountered by crops in the field. Toward this goal, a controlled, sublethal,
      moderate drought (mDr) treatment system was developed in Arabidopsis (Arabidopsis
      thaliana) as a reproducible assay for the dissection of plant responses to
      drought. The drought assay was validated using Arabidopsis mutants in abscisic
      acid (ABA) biosynthesis and signaling displaying drought sensitivity and in
      jasmonate response mutants showing drought resistance, indicating the crucial
      role of ABA and jasmonate signaling in drought response and acclimation. A
      comparative transcriptome analysis of soil water deficit drought stress
      treatments revealed the similarity of early-stage mDr to progressive drought,
      identifying common and specific stress-responsive genes and their promoter cis
      regulatory elements. The dissection of mDr stress responses using a time-course
      analysis of biochemical, physiological, and molecular processes revealed early
      accumulation of ABA and induction of associated signaling genes, coinciding with
      a decrease in stomatal conductance as an early avoidance response to drought
      stress. This is accompanied by a peak in the expression of expansin genes
      involved in cell wall expansion, as a preparatory step toward drought acclimation
      by the adjustment of the cell wall. The time-course analysis of mDr provides a
      model with three stages of plant responses: an early priming and preconditioning
      stage, followed by an intermediate stage preparatory for acclimation, and a late
      stage of new homeostasis with reduced growth.

PMID- 20808002
TI  - Radiographic assessment of congenital C2-3 synostosis.
AB  - PURPOSE: To evaluate the morphologies of congenital C2-3 synostosis in 25
      patients. METHODS: Radiographs of 11 males and 14 females aged 5 to 74 years with
      congenital C2-3 synostosis were reviewed. All cases were found incidentally on
      radiographs when presenting with neck/shoulder discomfort/pain. RESULTS: 13 of
      the patients had spondylosis in 21 segments: C1-2 (n=1) and C3-4 (n=1), C4-5
      (n=7), C5-6 (n=9), and C6-7 (n=3). Of whom 12 had normal sagittal alignment and
      one had kyphotic synostosis (who developed compensatory hyperlordosis of the
      caudal mobile segments and subsequent spondylosis at C3-4 and C5 retrolisthesis).
      The remaining 12 patients had no spondylosis and had normal sagittal alignment,
      but had other associated pathologies including disc herniation at C3-4, C1 ring
      hypoplasia, and calcification of the nuchal ligament. CONCLUSION: Normally
      aligned congenital synostosis of C2-3 is rarely associated with a junctional
      problem, whereas a kyphotic synostosis is associated with a caudal junctional
      problem. Spondylosis developing after age 40 years is not associated with C2-3
      synostosis.

PMID- 20808003
TI  - Mortality after vertebral fractures in a Japanese population.
AB  - PURPOSE: To assess the association between vertebral fractures and mortality.
      METHODS: 419 women and 210 men aged 60 to 98 (mean, 73) years participated in an
      osteoporosis screening exercise. Patient age, gender, comorbidity, lumbar pain,
      smoking, and alcohol consumption were recorded, as were the number of vertebral
      fractures and bone mineral density. Vertebral fractures were evaluated using
      lateral radiographs and quantitative morphometry. Anterior, central, and
      posterior vertebral heights were measured; vertebral fractures were defined as a
      decrease of more than or equal to 20% in any of these heights. RESULTS: 131 (21%)
      of the participants had vertebral fractures. At the 10-year follow-up, 121 (19%)
      of the participants (55 men and 66 women) had died; 43 of them had vertebral
      fractures and 78 did not. The respective 10-year survival rates for participants
      with and without vertebral fractures were 69% and 86% (p<0.0001). The survival
      rate was lower in those with greater number of vertebral fractures (76% for those
      with one or 2 fractures and 50% for those with 3 fractures or more). Multiple
      regression analysis showed that advanced age (p<0.0001), male gender (p=0.003),
      and presence of vertebral fractures (p=0.013) correlated significantly with
      survival. CONCLUSION: The presence and number of vertebral fractures were
      associated with mortality. Prevention of vertebral fractures may be important for
      improving the prognosis of patients with osteoporosis.

PMID- 20808004
TI  - Occult posterior pelvic ring fractures in elderly patients with osteoporotic
      pubic rami fractures.
AB  - PURPOSE: To evaluate postoperative walking status of elderly patients with
      osteoporotic pubic rami fractures with or without posterior pelvic ring
      fractures. METHODS: 33 women and 4 men aged 66 to 95 (mean, 85) years presented
      with osteoporotic pubic rami fractures after a fall. 22 (59%) of the patients had
      additional posterior pelvic ring fractures (9 had lateral compression type-II
      fractures involving the ilium and 13 had lateral compression type-I fractures
      involving the sacroalar region). Seven of the 9 patients with lateral compression
      type-II fractures underwent open reduction and internal fixation using plates
      and/ or screws. The remaining 30 patients were treated conservatively. RESULTS:
      Postoperative walking status was similar in elderly patients with osteoporotic
      pubic rami fractures with or without posterior pelvic ring fractures. CONCLUSION:
      Posterior pelvic ring fractures are easily missed in elderly patients with pubic
      rami fractures. Routine computed tomography of the pelvis is useful in making the
      diagnosis.

PMID- 20808005
TI  - Effect of lag-screw positions on modes of fixation failure in elderly patients
      with unstable intertrochanteric fractures of the femur.
AB  - PURPOSE: To investigate the effect of lag-screw positions in the femoral head on
      modes of fixation failure. METHODS: 591 patients aged 65 years or older underwent
      sliding compression screw fixation for type A(1) (n=249) and type A(2) (n=342)
      intertrochanteric fractures of the femur after low-energy injuries. There were 18
      cases of fixation failure; in 13 (group 1) the lag screw was placed in the
      central-central area, and in 5 (group 2) in the inferior 1/3-central area.
      Clinical variables of the 2 groups were compared. RESULTS: All 18 cases of
      fixation failure were actually type A(23) and misinterpreted as type A(22)
      fractures. In 13 cases, failure was attributable to cut-out of the lag screws at
      the superolateral edge of the femoral head. In 3 cases, failure was attributable
      to telescoping and more than 2 cm shortening of the femur. In one case, failure
      was due to penetration of the lag screw into the acetabulum. In another case,
      failure was due to plate loosening with breakage of cortical screws. In the 13
      cases with cut-out of the lag screw (group 1), the lag screw was placed in the
      central-central area (p<0.001). In the remaining 5 cases with no cut-out (group
      2), the lag screw was placed in the inferior 1/3-central area (p<0.01).
      Complications occurred significantly earlier in group 1 than in group 2 patients
      (2.6 vs. 4.6 months, p=0.02). The tip-apex distance was significantly shorter in
      group 1 than in group 2 patients (19 vs. 30 mm, p<0.001). CONCLUSION:
      Misinterpretation of type A(23) fractures as type A(22) may lead to fixation
      failure. Operative treatment should not be delayed once complications occur. The
      positions of the lag screw may affect the mode of fixation failure.

PMID- 20808006
TI  - Cemented Thompson versus cemented bipolar prostheses for femoral neck fractures.
AB  - PURPOSE: To compare early functional outcomes, complications, and mortality in
      elderly patients treated with the less costly, cemented Thompson prosthesis or
      the cemented bipolar prosthesis in order to identify factors affecting outcomes.
      METHODS: Records of 303 patients with femoral neck fractures treated with the
      cemented Thompson monoblock prosthesis (n=206) or the cemented bipolar prosthesis
      (n=97) were reviewed. The choice of prosthesis was solely determined by surgeon's
      preference. Data relating to patient demographics, clinical and residential
      status, mobility, mental function, mortality, and complications during
      hospitalisation and rehabilitation were collected. RESULTS: After adjusting for
      confounding variables, independent postoperative indoor mobility was associated
      with preoperative indoor mobility (p=0.002) and mental function (p=0.001),
      whereas postoperative outdoor mobility was associated with preoperative outdoor
      mobility (p=0.003), daily living activity (p=0.02), and mental function (p=0.02).
      Mortality within 6 months was only associated with poor mental function
      (p=0.009). At 6-month follow-up, there was no significant difference between the
      2 types of prosthesis in terms of functional outcomes, mortality and complication
      rates. CONCLUSION: In elderly patients with limited mobility, treatment with the
      bipolar prosthesis was not associated with better short-term outcomes than those
      receiving the Thompson prosthesis.

PMID- 20808007
TI  - Mid- to long-term outcome of cementless total hip arthroplasty in younger
      patients.
AB  - PURPOSE: To assess mid- to long-term outcomes of cementless primary total hip
      arthroplasty (THA) in younger patients. METHODS: Records of 28 women and 34 men
      (75 hips) aged 18 to 55 (mean, 38) years who underwent primary THA using a
      hydroxyapatite-coated stem and a threaded cup and had been followed up for a mean
      of 10 (6-15) years were reviewed. 13 of the patients had bilateral THAs. Clinical
      and radiographic outcomes were evaluated. RESULTS: After a minimum follow-up of 7
      (range, 7-14) years, 12 (16%) of the hips were revised, of which 8 (11%) were for
      the cup. The causes for revision were late deep infections (n=2), aseptic
      loosening of the cup (n=4), and polyethylene wear (n=6). No stem was revised for
      aseptic loosening. Osteolysis was noted in 24 (38%) hips. Of the 63 unrevised
      hips, the mean Harris Hip Score was 92 (range, 45-100) and the mean D'Aubigne and
      Postel score was 17 (range, 9-18). The survival of the threaded cup was 88% at 10
      years, using revision surgery as the end point. 27 (41%) of the hips showed signs
      of polyethylene wear; 15 were >2 mm. CONCLUSION: In younger patients undergoing
      THA, rates of polyethylene wear and pelvic osteolysis are high, and thus long
      term follow-up is crucial.

PMID- 20808008
TI  - Risk factors for early dislocation after total hip arthroplasty: a matched case
      control study.
AB  - PURPOSE: To evaluate risk factors for early dislocation after primary total hip
      arthroplasty (THA). METHODS: Records of 175 cases with dislocation during
      hospitalisation after THA and 651 controls without dislocation were reviewed.
      Cases and controls were matched for age, gender, body mass index classification,
      primary diagnosis, cup design, hospital, and year of intervention. Version and
      inclination of the acetabular component and version of the femoral component were
      assessed intra- and post-operatively. Various risk factors were analysed,
      including surgical approach, cup positioning, combined cup and stem positioning,
      and femoral head size. RESULTS: The posterior approach was 6 fold more prone to
      dislocation (odds ratio [OR]=6.3, p<0.018) than the anterolateral or straight
      lateral approach. With regard to combined cup and stem positioning, the
      acceptable position was at significantly higher risk of dislocation than the
      ideal position (OR=2.59, p=0.033). Larger femoral head sizes were associated with
      significantly lower risk of dislocation (OR=0.84, p=0.02). CONCLUSION: Surgical
      approach, combined cup and stem positioning, and femoral head size were
      significant risk factors for dislocation during hospitalisation.

PMID- 20808009
TI  - Cementing polyethylene liners into non-modular acetabular components in revision
      total hip arthroplasty.
AB  - PURPOSE: To review mid-term results after replacing the polyethylene liner in a
      well-fixed acetabular shell. METHODS: 22 patients underwent replacement of the
      polyethylene liner in a well-fixed acetabular shell using cementation. The inner
      surface of the metal shell was scored with grooves (1 to 2 mm deep) for cement
      interdigitation. Trial liners were used to assess the appropriate size, with an
      aim to provide at least 2 mm of an even cement mantle behind the polyethylene
      liner. None of the liners were constrained or lipped. Clinical and radiographic
      outcomes were evaluated, and Harris Hip Scores obtained. Radiographic loosening
      of the acetabular shell was recorded. Implant survival was evaluated using the
      Kaplan- Meier estimator. RESULTS: After a mean follow-up of 70 (range, 21-189)
      months, 17 patients had stable hips and their mean Harris Hip Score was 89
      (range, 72-93). Four patients underwent re-revision after 28 to 108 months for
      aseptic loosening of the acetabular shell (n=2) and recurrent dislocation (n=2).
      One patient showed radiographic evidence of acetabular migration but was stable.
      The femoral components of all patients were stable. 92% of patients had good-to
      excellent results. Implant survival at 60 months was 81% (95% confidence interval
      [CI], 51-94%); it became 91% (95% CI, 61-99%) if reductions for dislocations were
      excluded. CONCLUSION: Cementation of an undersized polyethylene liner into a non
      modular shell is one option for revision of a well-fixed acetabular shells.
      Nonetheless, further follow-up is required to determine if it remains a viable
      option in the long term. If there is any doubt about the stability of the
      acetabular shell, a complete revision should be performed.

PMID- 20808010
TI  - Proximal femoral medullary canal diameters in Indians: correlation between
      anatomic, radiographic, and computed tomographic measurements.
AB  - PURPOSE: To compare anatomic, radiographic, and computed tomographic (CT)
      measurements of the proximal femur in an Indian population. METHODS: 26 left and
      24 right dried cadaveric femurs were obtained. Each femur was divided into
      segments at 10 cross-sectional levels from proximal to distal. At each level,
      anteroposterior (AP), lateral, 45-degree internal oblique, and 45-degree external
      oblique diameters of the medullary canal were measured using radiography and CT.
      To minimise magnification, the femur was placed over the film/board. The neck
      shaft angle, femoral head offset, neck length, and femoral head diameter were
      also measured. For anatomic measurements, the cross-sections of the medullary
      canal at levels 3 to 10 were measured using a calliper. Anatomic measurements
      were compared with radiographic and CT measurements, and the distortion
      calculated. Correlation between the 3 modalities was calculated using the Pearson
      correlation coefficient. Accuracy index of the 2 diagnostic modalities was
      measured, based on the differences between anatomic and radiographic/CT
      measurements. Lower accuracy indices indicated higher accuracy. RESULTS: On AP
      radiographs of all femurs, the mean femoral head diameter was 45 mm, the mean
      neck shaft angle was 132 degrees, the mean femoral head offset was 42 mm, and the
      mean neck length was 63 mm. With regard to medullary canal diameters, the
      radiographic and CT measurements were smaller than anatomic measurements at
      proximal levels, but similar at distal levels. Variations between femurs and
      between the 4 diameters at the same level were greater at proximal levels.
      CONCLUSIONS: Combined use of radiography and CT is recommended for preoperative
      assessment of implant size, particularly in uncemented arthroplasty where an
      optimal fit is essential for biological fixation.

PMID- 20808011
TI  - Differences in outcome between Maori and Caucasian patients undergoing total
      joint arthroplasty for osteoarthritis.
AB  - PURPOSE: To compare differences in outcome between Maori and Caucasian patients
      undergoing total joint arthroplasty for osteoarthritis. METHODS: 45 men and 45
      women aged 43 to 87 years who underwent total hip (n=54) or total knee (n=36)
      arthroplasties by a single surgeon and were followed up for at least one year
      were prospectively studied. Patients were classified according to American
      Society of Anesthesiologists (ASA) score. Preoperative comorbidity, length of
      hospital stay, postoperative complications, and pre- and post-operative outcomes
      in the 2 groups were compared. RESULTS: Maori patients were more likely than
      Caucasian patients to be obese (body mass index of >30 kg/m square) [37% vs.
      15%], diabetic (15% vs. 5%), and smokers (32% vs. 13%). Postoperative
      complication rates and the lengths of hospital stay in the 2 groups were not
      significantly different. The ASA score correlated positively with the length of
      hospital stay; higher ASA scores predicted more prolonged recovery. CONCLUSION:
      Maori patients were more likely than Caucasian patients to have preoperative
      comorbidities, but their postoperative length of hospital stay and complication
      rates were not significantly different.

PMID- 20808012
TI  - Femoral tunnel widening after quadrupled hamstring anterior cruciate ligament
      reconstruction.
AB  - PURPOSE: To evaluate the extent of femoral tunnel widening after quadrupled
      hamstring anterior cruciate ligament reconstruction using femoral cross pin
      fixation in contrast to bioabsorbable screw fixation augmented with Endopearl.
      METHODS: 16 patients underwent cross pin femoral fixation and the next 15
      underwent bioabsorbable screw fixation augmented with Endopearl. The patients
      were evaluated radiographically for femoral tunnel widening. Standard
      posteroanterior radiographs of the knee in full extension were taken at
      postoperative year 2 and 5. The tunnel width was measured at the opening, the
      widest and the most proximal parts of the femoral tunnel. RESULTS: In the femoral
      cross pin and bioabsorbable screw fixations, the mean femoral tunnel sizes were
      7.6 and 8.0 mm, respectively. The overall mean tunnel widening at all measured
      sites were 2.7 and 1.8 mm at the 2-year follow-up and were 2.5 and 1.8 mm at the
      5-year follow-up, respectively. The femoral tunnel widening was greater in the
      cross pin than the bioabsorbable screw group, but only the difference in the most
      proximal part was significant (p=0.01 at year 2 and p<0.001 at year 5).
      CONCLUSION: Femoral tunnel widening was greater in femoral cross pin fixation,
      probably related to the windshield-wiper and bungee-cord effects. It usually
      occurred in the first 2 years after the operation and remained static thereafter.

PMID- 20808013
TI  - Continuous infiltration of local anaesthetic following total knee arthroplasty.
AB  - PURPOSE: To determine whether continuous infiltration of local anaesthetic can
      reduce the pain score and morphine use over 48 hours after total knee
      arthroplasty (TKA). METHODS: 11 men and 43 women aged 50 to 82 years who
      underwent unilateral TKA for osteoarthritis were recruited. They were randomised
      into 3 groups. In group 1, 17 patients who acted as controls received patient
      controlled analgesia (PCA) with intravenous morphine for 48 hours. In group 2, 16
      patients received continuous infiltration of bupivacaine to the subcutaneous
      tissue and intra-articular space for 48 hours, in addition to PCA. In group 3, 21
      patients received an intra-articular injection of local anaesthetic, followed by
      continuous infiltration of bupivacaine to the subcutaneous tissue and
      intraarticular space for 48 hours, in addition to PCA. For each patient, a visual
      analogue score (VAS) for pain was recorded postoperatively at 2, 4, 6, 12, 24,
      36, and 48 hours. The total amount of morphine used was recorded at 24 and 48
      hours. RESULTS: Over 48 hours, the VAS for pain and morphine use was
      significantly higher in controls than patients in groups 2 and 3. CONCLUSION:
      Continuous infiltration of local anaesthetic into the intra-articular space and
      subcutaneous tissues, in addition to PCA with intravenous morphine, provides
      significantly more pain relief and reduces morphine use.

PMID- 20808014
TI  - Resection and arthrodesis of the knee joint for giant cell tumours of bone.
AB  - PURPOSE: To evaluate functional outcomes and complications following resection
      and arthrodesis of the knee for giant cell tumours (GCTs) of bone, in comparison
      to treatment by endoprosthetic replacements reported elsewhere. METHODS: 18 men
      and 14 women aged 18 to 40 (mean, 28) years underwent resection and arthrodesis
      of the knee for GCTs of bone involving the distal femur (n=17) and proximal tibia
      (n=15). After wide resection, 2 struts were fashioned from the harvested fibula/
      fibulae and inserted into the medullary canal at the resected ends of the tibia
      and femur. The corresponding ends of the struts were inserted into peg holes made
      in the unaffected condyles in a divergent fashion. The knee was arthrodesed in 5
      to 10 degrees of flexion, with the limb kept 1 cm short. A 95-degree AO condylar
      bladeplate (10-12 holes) was fixed at the resected ends, with a minimum of 8
      cortices purchase. Cancellous bone grafts were placed transversely along the
      struts and circumferentially over the host-graft junctions. Outcomes and
      complications were evaluated and compared with those of endoprosthetic
      arthroplasty reported elsewhere. RESULTS: Patients were followed up for a mean of
      8 (range, 3-12) years. The mean size of the tumours was 10x8x6 cm. All patients
      achieved arthrodesis and full weight bearing without pain within 6 to 10 (mean,
      6) months. No shortening, loss of alignment, loosening, implant breakage ensued.
      One patient had a deep infection and absorption at the host-graft junction.
      Another had a stress fracture of the fibular strut after plate removal. Two
      patients had a transient peroneal nerve palsy. One patient had local recurrence
      and extensive fungation and underwent amputation. The mean functional score was
      26 (87% of the full score), compared to 66 to 85% in endoprosthetic arthroplasty
      reported elsewhere. CONCLUSION: Arthrodesis is a viable alternative to customised
      arthroplasty and provides a long-lasting and cost-effective reconstruction for
      average patients in developing countries.

PMID- 20808015
TI  - Predictive factors for recurrence of simple bone cyst of the proximal humerus.
AB  - PURPOSE: To evaluate factors predictive of recurrence following curettage of
      simple bone cysts (SBCs) in the proximal humerus. METHODS: Records of 29 male and
      3 female patients aged 3 to 22 (mean, 11) years who underwent curettage with or
      without bone grafting for a solitary SBC in the proximal humerus were reviewed.
      The appearance, size, location, activity level, and fracture pattern of each cyst
      were recorded. The cyst index indicated the risk of refracture. Recurrence was
      defined as a refracture or enlargement of the cyst. RESULTS: 31 patients
      presented with a pathological fracture. The main symptoms were pain (n=30), loss
      of function (n=22), and mass/swelling (n=15). 25 patients gave a history of
      trauma. The duration of symptoms was less than one month. 10 patients had
      recurrence after a mean of 10 (range, 4-27) months; 5 were refractures and
      another 5 were enlargement of the cysts. Six were treated conservatively and
      eventually healed, whereas 4 underwent further curettage. Factors predictive of
      recurrence were patient age 5 years or younger (p=0.014), right-sided cyst
      (p=0.01), larger cyst (p=0.039), multilocular cyst (p=0.004) and unimpacted
      fracture (p=0.04). Recurrence was not related to gender, cyst location, or cyst
      activity level. CONCLUSION: Most SBCs heal even if the fracture is treated
      expectantly. SBCs should be left alone unless symptomatic. If curettage is
      performed, grafts or bone substitutes should be used. More aggressive treatment
      might be necessary for unimpacted fractures to minimise the risk of recurrence.

PMID- 20808016
TI  - Lateral closing wedge osteotomy with or without medialisation of the distal
      fragment for cubitus varus.
AB  - PURPOSE: To compare treatment outcomes after closing wedge osteotomy and plate
      fixation for cubitus varus deformity undertaken with or without medialisation of
      the distal fragment. METHODS: Records of 21 men and 16 women aged 20 to 34 years
      who underwent closing wedge osteotomy and plate fixation for cubitus varus
      deformity with (n=21) or without (n=16) medialisation of the distal fragment were
      reviewed. A daily alternate flexion-extension splinting was applied for one week
      for early restoration of full range of motion. The carrying angle and range of
      motion of the elbow were measured. RESULTS: All patients regained the normal
      carrying angle and range of motion; none had loss of fixation or limitation in
      range of motion exceeding 10 degrees. Outcomes were excellent in 23 patients and
      good in 9. A small bony prominence over the lateral condylar region ('lazy S'
      deformity) was noted in group-1 but not group-2 patients. CONCLUSION: Closing
      wedge supracondylar osteotomy with medialisation of the distal fragment was an
      effective treatment for cubitus varus deformity and minimised the risk of 'lazy
      S' deformity.

PMID- 20808017
TI  - Risk factors for surgical wound infection in HIV-positive patients undergoing
      surgery for orthopaedic trauma.
AB  - PURPOSE: To identify risk factors associated with surgical wound infection in
      patients infected with human immunodeficiency virus (HIV) undergoing surgery for
      orthopaedic trauma. METHODS: Records of 29 male and 7 female HIV-positive
      patients aged 18 to 47 years who underwent surgery for orthopaedic trauma were
      reviewed. Data on HIV-specific variables (HIV clinical classification, CD4+
      lymphocyte count) and highly active antiretroviral therapy were retrieved, as
      were data on wound class, fracture type, surgery type, surgical wound infections,
      and outcomes. Possible risk factors associated with surgical wound infection were
      analysed. RESULTS: The median follow-up period was 27 (range, 19-41) months. Of
      the 36 patients, 14 (39%) developed surgical wound infections (4 were deep and 10
      superficial). 89% and 67% of them were in HIV clinical category B and in CD4+ T
      lymphocyte category 3, respectively. 12 of these infections resolved after
      debridement and prolonged antibiotic treatment, and 2 developed chronic
      osteomyelitis. Four of the patients had non-union. Surgical wound infections were
      associated with HIV clinical category B (p<0.001), CD4+ T-lymphocyte category of
      more than or equal to 2 (p=0.041), and contaminated wounds (p=0.003). CONCLUSION:
      Identification of risk factors may help minimise morbidity in HIV-positive
      patients.

PMID- 20808019
TI  - Atlanto-axial deformity secondary to a neglected odontoid fracture: a report of
      six cases.
AB  - We reviewed 6 patients with atlanto-axial (C1-2) deformities secondary to
      neglected odontoid fractures. All patients (except one with recent injury) were
      asymptomatic for a long period before development of neck pain or myelopathy,
      despite obvious subluxation and kyphotic deformities at the C1-2 joint complex.
      Patients were treated conservatively, except for one who underwent posterior
      spinal fusion and occiput-to-C2 decompression for progressive myelopathy. The
      reactive new bone formation around the odontoid fracture may play a role in
      preventing further movement and development of myelopathy. Conservative treatment
      should be considered for neglected odontoid fractures in elderly patients with
      stable non-progressive C1-2 deformity.

PMID- 20808018
TI  - Effect of risedronate on bone resorption during consolidation phase of
      distraction osteogenesis: a rabbit model.
AB  - PURPOSE: To evaluate the effects of continuous local injection of risedronate in
      the prevention of bone resorption in a lengthened segment. METHODS: 11 male
      rabbits underwent subperiosteal osteotomy of the left tibia and an external
      fixator was applied anteromedially. After a lag phase of one week, a 2-week
      distraction phase and a 5-week consolidation phase followed. Risedronate was
      continuously injected into the centre of the distracted segment at a rate of 10
      micro g/kg/day during the first 14 days of consolidation by a subcutaneously
      implanted osmotic pump. A control group received purified buffer solution (PBS)
      using the same protocol. The lengthened bone segments were evaluated using
      radiography, quantitative computed tomography, and 3-point bending mechanical
      test. RESULTS: Risedronate injection prevented osteopenia as compared to PBS
      injection. The mean bone mineral content, volumetric density and cross-sectional
      area of the lengthened segments were significantly higher in the risedronate
      group than in controls (as much as 65%, 30%, and 25%, respectively). There was no
      significant difference between the 2 groups regarding the ultimate load to
      failure. CONCLUSION: Continuous local injection of risedronate into the
      lengthened segment can prevent osteopenia during distraction osteogenesis but
      fails to enhance mechanical strength of newly distracted segments.

PMID- 20808020
TI  - Concomitant fungal and bacterial atlanto-axial osteomyelitis: a case report.
AB  - Concomitant fungal and bacterial atlanto-axial osteomyelitis in immunocompetent
      individuals is rare. We report one such patient who underwent transoral anterior
      decompression and posterior occipital cervical fusion, together with antibiotic
      and antifungal treatment. At 16-month follow-up, the patient had made a full
      recovery with solid fusion. Prompt diagnosis requires a high degree of clinical
      suspicion, with timely use of modern imaging modalities. When the diagnosis is
      early, antibiotic treatment alone should suffice.

PMID- 20808021
TI  - Pseudoaneurysm and intramuscular haematoma after dynamic hip screw fixation for
      intertrochanteric femoral fracture: a case report.
AB  - We report the case of an 83-year-old woman who developed a pseudoaneurysm of the
      profunda femoris artery after dynamic hip screw fixation for an intertrochanteric
      femoral fracture. 23 days after the fixation, radiological investigations
      including colour Doppler ultrasonography and computed tomographic angiography
      identified a pseudoaneurysm surrounded by a large intramuscular haematoma close
      to the profunda femoris. The patient underwent emergency evacuation and was under
      intensive care for 3 days and was discharged 6 weeks later, with no
      complications. At one-year follow-up, the wound and fracture had healed, but the
      patient was confined to a wheelchair. A high index of clinical suspicion and
      radiological imaging are necessary for making the diagnosis.

PMID- 20808022
TI  - Intra-articular synovial cyst of the knee joint: a case report.
AB  - Synovial cysts occur secondary to injury, mucinous degeneration or tumours. We
      report a patient with snapping of the knee joint caused by a synovial cyst
      located near the patellofemoral joint which developed as a result of minor
      trauma.

PMID- 20808023
TI  - Bilateral ganglion cysts of the cruciate ligaments: a case report.
AB  - Symptomatic ganglion cysts of the cruciate ligaments are rare, and bilateral
      cases are extremely rare, with only one reported case in the literature. We
      report a case of bilateral cruciate ligament ganglion cysts successfully treated
      with arthroscopic resection, and review the literature regarding aetiology,
      diagnosis and management.

PMID- 20808024
TI  - Intrathoracic fracture-dislocation of the humeral head: a case report.
AB  - Fracture-dislocation of the humeral head into the thoracic cavity is a rare
      injury. We present one such case in a 70-year-old woman. She presented with a 4
      part fracture-dislocation of the proximal humerus, with displacement of the
      humeral head into the thoracic cavity. She had no signs of acute distress or
      hemodynamic instability. She underwent hemiarthroplasty of the right shoulder,
      but the humeral head fragment could not be removed. At 27-month follow-up, the
      patient had limited mobility of her right shoulder due to axillary nerve palsy
      but no pain or intrathoracic complications. In the absence of intrathoracic
      complications, the removal of the humeral head may not be necessary.

PMID- 20808025
TI  - Cost comparison of femoral head banking versus bone substitutes.

PMID- 20808026
TI  - Direct MRI detection of the neuronal magnetic field: the effect of the dendrite
      branch.
AB  - In recent years, neuronal current MRI (nc-MRI) was proposed as a new imaging
      method to directly map the magnetic field change caused by neuronal activity. Nc
      MRI could offer improved spatial and temporal resolution compared to blood
      hemodynamics-based functional magnetic resonance imaging (fMRI). In this paper,
      with a finite current dipole as the model of dendrite or dendrite branch, we
      investigated the spatial distribution of the magnetic field generated by
      synchronously activated neurons to evaluate the possibility of nc-MRI. Our
      simulations imply that the existence of a dendrite branch may not only increase
      the strength of the neuronal magnetic field (NMF), but also raise the non-uniform
      and unsymmetry of the NMF; therefore, it can enhance the detectability of the
      neuronal current magnetic field by MRI directly. The results show that the signal
      phase shift is enlarged, but it is unstable and is still very small, <<1 radian,
      while the magnitude signal may be strong enough for a typical MRI voxel to be
      detected. We suggest making further efforts to measure the magnitude signal which
      may induce a large effect in an nc-MRI experiment.

PMID- 20808027
TI  - Dosimetric properties of Gafchromic(R) EBT films in medical carbon ion beams.
AB  - High spatial resolution is desired for dosimetrical verification of patient plans
      for radiotherapy treatments employing scanned ion beams. This is provided by
      Gafchromic EBT film, the ancestor of currently available EBT2 films. In this
      contribution, dosimetric properties of EBT films were investigated. Measurements
      of depth response were performed for monoenergetic fields (250 MeV/u) for
      different ion fluences as well as for an energy-modulated spread-out Bragg peak
      of 5 x 5 x 5 cm(3) in 10 cm depth. The films were positioned perpendicular to the
      incoming carbon ion beams. The observed quenching of the response relative to the
      same dose of photons was quantified by the relative efficiency. In monenenergetic
      beams, a relative efficiency of about 0.73 was found in the plateau, 0.4 in the
      peak and 0.55 in the tail region. No dependence of the relative efficiency on the
      ion fluence was observed well beyond the clinically used levels. This gives a
      constant peak to plateau ratio, which is about 1.8 times lower than that for the
      delivered dose. In the spread-out Bragg peak, the relative efficiency was found
      to decrease from 0.64 to 0.54 toward the distal end. Thus when aiming for a
      prediction of the film response in mixed ion beams, the efficiency of the film
      has to be parametrized as a function of the ion type and energy over the whole
      ion spectrum. In addition, the relative water-equivalent range of EBT films was
      measured here to be 1.291 +/- 0.015.

PMID- 20808028
TI  - The influence of the reflective environment on the absorption of a human male
      exposed to representative base station antennas from 300 MHz to 5 GHz.
AB  - The environment is an important parameter when evaluating the exposure to radio
      frequency electromagnetic fields. This study investigates numerically the
      variation on the whole-body and peak spatially averaged-specific absorption rate
      (SAR) in the heterogeneous virtual family male placed in front of a base station
      antenna in a reflective environment. The SAR values in a reflective environment
      are also compared to the values obtained when no environment is present (free
      space). The virtual family male has been placed at four distances (30 cm, 1 m, 3
      m and 10 m) in front of six base station antennas (operating at 300 MHz, 450 MHz,
      900 MHz, 2.1 GHz, 3.5 GHz and 5.0 GHz, respectively) and in three reflective
      environments (a perfectly conducting wall, a perfectly conducting ground and a
      perfectly conducting ground + wall). A total of 72 configurations are examined.
      The absorption in the heterogeneous body model is determined using the 3D
      electromagnetic (EM) finite-difference time-domain (FDTD) solver Semcad-X. For
      the larger simulations, requirements in terms of computer resources are reduced
      by using a generalized Huygens' box approach. It has been observed that the ratio
      of the SAR in the virtual family male in a reflective environment and the SAR in
      the virtual family male in the free-space environment ranged from -8.7 dB up to
      8.0 dB. A worst-case reflective environment could not be determined. ICNIRP
      reference levels not always showed to be compliant with the basic restrictions.

PMID- 20808029
TI  - A multi-region algorithm for markerless beam's-eye view lung tumor tracking.
AB  - Methods that allow online lung tumor tracking during radiotherapy are desirable
      for a variety of applications that have the potential to vastly improve treatment
      accuracy, dose conformity and sparing of healthy tissue. Several publications
      have proposed the use of an on-board kV x-ray imager to assess the tumor location
      during treatment. However, there is some concern that this strategy may expose
      the patient to a significant amount of additional dose over the course of a
      typical radiotherapy treatment. In this paper we present an algorithm that
      utilizes the on-board portal imager of the treatment machine to track lung
      tumors. This does not expose the patient to additional dose, but is somewhat more
      challenging as the quality of portal images is inferior when compared to kV x-ray
      images. To quantify the performance of the proposed algorithm we retrospectively
      applied it to portal image sequences retrieved from a dynamic chest phantom study
      and an SBRT treatment performed at our institution. The results were compared to
      manual tracking by an expert. For the phantom data the tracking error was found
      to be smaller than 1 mm and for the patient data smaller than 2 mm, which was in
      the same range as the uncertainty of the gold standard.

PMID- 20808030
TI  - Quantitative x-ray dark-field computed tomography.
AB  - The basic principles of x-ray image formation in radiology have remained
      essentially unchanged since Rontgen first discovered x-rays over a hundred years
      ago. The conventional approach relies on x-ray attenuation as the sole source of
      contrast and draws exclusively on ray or geometrical optics to describe and
      interpret image formation. Phase-contrast or coherent scatter imaging techniques,
      which can be understood using wave optics rather than ray optics, offer ways to
      augment or complement the conventional approach by incorporating the wave-optical
      interaction of x-rays with the specimen. With a recently developed approach based
      on x-ray optical gratings, advanced phase-contrast and dark-field scatter imaging
      modalities are now in reach for routine medical imaging and non-destructive
      testing applications. To quantitatively assess the new potential of particularly
      the grating-based dark-field imaging modality, we here introduce a mathematical
      formalism together with a material-dependent parameter, the so-called linear
      diffusion coefficient and show that this description can yield quantitative dark
      field computed tomography (QDFCT) images of experimental test phantoms.

PMID- 20808031
TI  - Semi-automated segmentation of the sigmoid and descending colon for radiotherapy
      planning using the fast marching method.
AB  - A fast and accurate segmentation of organs at risk, such as the healthy colon,
      would be of benefit for planning of radiotherapy, in particular in an adaptive
      scenario. For the treatment of pelvic tumours, a great challenge is the
      segmentation of the most adjacent and sensitive parts of the gastrointestinal
      tract, the sigmoid and descending colon. We propose a semi-automated method to
      segment these bowel parts using the fast marching (FM) method. Standard 3D
      computed tomography (CT) image data obtained from routine radiotherapy planning
      were used. Our pre-processing steps distinguish the intestine, muscles and air
      from connective tissue. The core part of our method separates the sigmoid and
      descending colon from the muscles and other segments of the intestine. This is
      done by utilizing the ability of the FM method to compute a specified minimal
      energy functional integrated along a path, and thereby extracting the colon
      centre line between user-defined control points in the sigmoid and descending
      colon. Further, we reconstruct the tube-shaped geometry of the sigmoid and
      descending colon by fitting ellipsoids to points on the path and by adding
      adjacent voxels that are likely voxels belonging to these bowel parts. Our
      results were compared to manually outlined sigmoid and descending colon, and
      evaluated using the Dice coefficient (DC). Tests on 11 patients gave an average
      DC of 0.83 (+/-0.07) with little user interaction. We conclude that the proposed
      method makes it possible to fast and accurately segment the sigmoid and
      descending colon from routine CT image data.

PMID- 20808034
TI  - Electrodeposition of ZnO nanorod arrays on ZnO substrate with tunable orientation
      and optical properties.
AB  - The electrodeposition of ZnO nanorods on ZnO:Al films with different orientations
      is reported. The influence of the total charge exchanged during electrodeposition
      on the nanorod's geometry (length, diameter, aspect ratio and surface density)
      and the optical transmission properties of the nanorod arrays is studied on a
      [0001]-oriented ZnO:Al substrate. The nanorods are highly vertically oriented
      along the c axis, following the lattice matching with the substrate. The growth
      on a [1010] and [1120] ZnO:Al-oriented substrate with c axis parallel to the
      substrate leads to a systematic deviation angle of 55 degrees from the
      perpendicular direction. This finding has been explained by the occurrence of a
      minority orientation with the [1011] planes parallel to the surface, with a
      preferential growth on corresponding [0001] termination. Substrate crystalline
      orientation is thereby found to be a major parameter in finely tuning the
      orientation of the nanorod array. This new approach allows us to optimize the
      light scattering properties of the films.

PMID- 20808033
TI  - Rigorous surface enhanced Raman spectral characterization of large-area high
      uniformity silver-coated tapered silica nanopillar arrays.
AB  - Surface enhanced Raman spectroscopy (SERS) has been increasingly utilized as an
      analytical technique with significant chemical and biological applications (Qian
      et al 2008 Nat. Biotechnol. 26 83; Fujita et al 2009 J. Biomed. Opt. 14 024038;
      Chou et al 2008 Nano Lett.8 1729; Culha et al 2003 Anal. Chem. 75 6196; Willets K
      A 2009 Anal. Bioanal. Chem. 394 85; Han et al 2009 Anal. Bioanal. Chem. 394 1719;
      Sha et al 2008 J. Am. Chem. Soc. 130 17214). However, production of a robust,
      homogeneous and large-area SERS substrate with the same ultrahigh sensitivity and
      reproducibility still remains an important issue. Here, we describe a large-area
      ultrahigh-uniformity tapered silver nanopillar array made by laser interference
      lithography on the entire surface of a 6 inch wafer. Also presented is the
      rigorous optical characterization method of the tapered nanopillar substrate to
      accurately quantify the Raman enhancement factor, uniformity and repeatability.
      An average homogeneous enhancement factor of close to 10(8) was obtained for
      benzenethiol adsorbed on a silver-coated nanopillar substrate.

PMID- 20808032
TI  - Slowing the translocation of double-stranded DNA using a nanopore smaller than
      the double helix.
AB  - It is now possible to slow and trap a single molecule of double-stranded DNA
      (dsDNA), by stretching it using a nanopore, smaller in diameter than the double
      helix, in a solid-state membrane. By applying an electric force larger than the
      threshold for stretching, dsDNA can be impelled through the pore. Once a current
      blockade associated with a translocating molecule is detected, the electric field
      in the pore is switched in an interval less than the translocation time to a
      value below the threshold for stretching. According to molecular dynamics (MD)
      simulations, this leaves the dsDNA stretched in the pore constriction with the
      base-pairs tilted, while the B-form canonical structure is preserved outside the
      pore. In this configuration, the translocation velocity is substantially reduced
      from 1 bp/10 ns to approximately 1 bp/2 ms in the extreme, potentially
      facilitating high fidelity reads for sequencing, precise sorting, and high
      resolution (force) spectroscopy.

PMID- 20808035
TI  - Nanofluidic single-molecule sorting of DNA: a new concept in separation and
      analysis of biomolecules towards ultimate level performance.
AB  - Separation and separation-based analysis of biomolecules are fundamentally
      important techniques in the field of biotechnology. These techniques, however,
      depend on stochastic processes that intrinsically involve uncertainty, and thus
      it is not possible to achieve 100% separation accuracy. Theoretically, the
      ultimate resolution and sensitivity should be realized in a single-molecule
      system because of the deterministic nature of single-molecule manipulation. Here,
      we have proposed and experimentally demonstrated the concept of a 'single
      molecule sorter' that detects and correctly identifies individual single
      molecules, realizing the ultimate level of resolution and sensitivity for any
      separation-based technology. The single-molecule sorter was created using a
      nanofluidic network consisting of a single inlet channel that branches off into
      multiple outlet channels. It includes two major functional elements, namely a
      single-molecule detection and identification element and a flow path switching
      element to accurately separate single molecules. With this system we have
      successfully demonstrated the world's first single-molecule sorting using DNA as
      a sample molecule. In the future, we hope to expand the application of such
      devices to comprehensive sorting of single-proteins from a single cell. We also
      believe that in addition to the single-molecule sorting method reported here,
      other types of single-molecule based processes will emerge and find use in a wide
      variety of applications.

PMID- 20808036
TI  - Nanometric thin film membranes manufactured on square meter scale: ultra-thin
      films for CO2 capture.
AB  - Miniaturization and manipulation of materials at nanometer scale are key
      challenges in nanoscience and nanotechnology. In membrane science and technology,
      the fabrication of ultra-thin polymer films (defect-free) on square meter scale
      with uniform thickness (<100 nm) is crucial. By using a tailor-made polymer and
      by controlling the nanofabrication conditions, we developed and manufactured
      defect-free ultra-thin film membranes with unmatched carbon dioxide permeances,
      i.e. > 5 m(3) (STP) m(-2) h(-1) bar(-1). The permeances are extremely high,
      because the membranes are made from a CO(2) philic polymer material and they are
      only a few tens of nanometers thin. Thus, these thin film membranes have
      potential application in the treatment of large gas streams under low pressure
      like, e.g., carbon dioxide separation from flue gas.

PMID- 20808037
TI  - Diameter modulation by fast temperature control in laser-assisted chemical vapor
      deposition of single-walled carbon nanotubes.
AB  - Diameter modulation by fast temperature control in laser-assisted chemical vapor
      deposition (LCVD) was successfully achieved to tune the diameters of single
      walled carbon nanotubes (SWNTs) in different segments. Due to the inverse
      relationship between the SWNT diameter and the growth temperature, SWNTs with
      ascending diameters were obtained by reducing the LCVD temperature from high to
      low. The diameter-modulated SWNTs were integrated in electrodes to form field
      effect transistors (FETs) and to investigate their electronic transport
      properties. The SWNTs in the FET structures have electronic properties similar to
      Schottky diodes, indicating clear evidence of different bandgap structures at the
      two ends of the SWNTs. Raman spectroscopy, transmission electron microscopy, and
      electronic transport characteristics were studied to investigate the influence of
      temperature variation on the structural and electronic characteristics of the
      SWNTs.

PMID- 20808038
TI  - Selective fabrication of quasi-parallel single-walled carbon nanotubes on silicon
      substrates.
AB  - We have fabricated single-walled carbon nanotube (SWNT) arrays, about 85% of
      which are semiconducting. Fe nanoparticles, which were used as a catalyst, were
      produced simply and cheaply from Wistar rat blood. The SWNT arrays generally grow
      parallel to the gas flow. Hundreds of devices with varying SWNT density in the
      channel were measured and we found that the on-off ratio for such devices with
      the quasi-parallel, semiconducting-rich SWNTs in the channel can be easily
      increased via an electrical breakdown method. Thus, large-scale fabrication of
      FET devices is possible simply by controlling the width of the channel. Finally,
      we determined that the mobility of the devices reached 3900 cm(2) V(-1) s(-1).

PMID- 20808039
TI  - [Epidemiological view of fracture risk].
AB  - Incidence of hip fracture increases exponentially with age. Women had two times
      higher hip fracture incidence than men. Major risk factors for the hip fracture
      are age, sex, bone mineral density, and previous fracture and others, but each
      risk factor contributes differently to development of the fracture by sites.
      Factors related to fall are important role in developing hip fracture.

PMID- 20808040
TI  - [Vitamin D and risk of fracture].
AB  - Although an increase in vitamin D has a small effect on bone mineral density, it
      has an influence on fracture prevention. This may be explained by a mechanism of
      improvement of bone strength that does not necessarily depend on bone mineral
      density. The level of serum 25 (OH) D is low in hip fracture patients compared
      with non-fracture controls, which suggests that a background of vitamin D
      insufficiency may be involved in hip fracture. Vitamin D acts on skeletal muscle
      and nerve cells, and it has been reported that this has an effect on fall
      prevention. Furthermore, recent reports suggest a role of vitamin D in cognitive
      function and in other tissues not involving bone.

PMID- 20808041
TI  - [Vitamin K and fracture].
AB  - Vitamin K is well known for its role in the synthesis of a number of blood
      coagulation factors. Vitamin K is also an important factor for bone metabolism
      via gamma-carboxylation of vitamin K-dependent proteins such as osteocalcin,
      matrix Gla protein, and protein S. Recent studies suggest that there is potential
      vitamin K insufficiency in bone, even in sufficient vitamin K status for blood
      coagulation. In the present review, the studies concerning relationship between
      vitamin K status and fracture are reviewed.

PMID- 20808042
TI  - [Fall and fracture risk].
AB  - Falls and fall-related fractures are a major problem among older adults. These
      injuries often cause continuous pain, functional impairments, and mortality.
      While the majority of falls do not result in fractures, most fractures are due to
      falls. Especially, almost all hip fractures (95%) result from falls. And so, it
      is very important to analyze falls and risk factors for falls. A history of falls
      is the major independent predictor of future fall risk. To date, several
      strategies have been provided to control risk factors for fall. To prevent falls
      and fall-induced injuries and fractures, multicomponent exercise, home hazard
      assessment and modification and use of hip protectors have proven efficient.

PMID- 20808043
TI  - [Assessment of hip fracture risk related to the structure].
AB  - Bone strength is determined not only by BMD, but also by many other bone quality
      relating factors such as bone structure etc.. Hip fractures are the most serious
      fragile fractures, considering that controlling their risk factors will
      successfully prevent these fractures. Recently Hip structure (strength) analyses
      have become available during standard DXA measurements. Bending strength and
      stability of the bone can be determined by their obtained parameters such as
      section modulus, cross sectional area and buckling ratio. These parameters shift
      towards fragile by aging, especially remarkably reduce after 70 years. It has
      been reported that both anti-resorptive agents and anabolic PTH increase bone
      strength in different manner. Further progressed 3 dimensional femoral neck
      strength analysis using CT scanning are now under development.

PMID- 20808044
TI  - [Lifestyle-related hip fracture risk].
AB  - Proximal femoral fracture (PFF) has long become a target for intervention with
      pharmacologic agents and pharmacologic intervention has been shown to reduce the
      fracture risk at least by half, compared to placebo, but PFF still continues to
      increase in incidence. Causes of fracture include bone-related and other factors
      but data remains yet to be accumulated on the relationship between these causes
      and lifestyle-related factors, such as nutrition, exercise and lifestyle
      preferences, which should be essential to establishing osteoporosis as a
      lifestyle-related disease. Furthermore, despite the paucity of evidence on the
      relationship between PFF and lifestyle habits, consideration should be given to
      developing preventive measures against PFF which take into account the potential
      impact of lifestyle-related factors on the occurrence of PFF to produce positive
      results.

PMID- 20808045
TI  - [Fracture risk in secondary osteoporosis].
AB  - In this review, we focused on diabetes mellitus (DM) , chronic kidney disease
      (CKD) , and glucocorticoid-induced osteoporosis (GIO) , which frequently occurred
      in the clinical settings, to discuss hip fracture risk. In DM, either type 1 or
      type 2, fracture risk is elevated probably due to deteriorated bone quality and
      increased frequency of falls, because the risk is much higher than that expected
      by bone density. In CKD, especially in patients undergoing dialysis therapy, high
      risks of fractures in younger people and of mortality after fractures are
      striking. Even mild to moderate renal dysfunction has recently been reported to
      elevate fracture risk. In GIO, we reviewed some papers in terms of relationship
      between doses and duration of corticosteroids and fracture risk.

PMID- 20808046
TI  - [Dementia and fracture].
AB  - A high incidence of fractures, particularly of the hip, represents an important
      problem in patients with AD, who are prone to falls and may have osteoporosis.
      The odds ratio reported for fracture prevalence between elderly persons with and
      without AD is 6.9. We previously demonstrated that deficiency of 25
      hydroxyvitamin D due to sunlight deprivation and vitamin K deficiency due to
      malnutrition contributed to reduced bone mineral density in patients with AD and
      were associated with a high risk of hip fracture. Treatment with menatetrenone,
      risedronate or regular sunlight exposure are safe and effective in increasing
      bone mass and reducing the risk of hip fracture in patients with AD.

PMID- 20808047
TI  - [Surgical treatment of proximal femoral fracture].
AB  - Surgical treatment of proximal femoral fracture is one of the most common
      surgeries for orthopaedic surgeon. Recent improvements of implant and surgical
      technique brought the change of postoperative physical therapy, shortened
      hospital stay and increased patient's activity. For intra-articular femoral neck
      fracture, internal fixation or artificial arthroplasty is applied depending on
      displacement of fracture site. On the other hand, internal fixation is usually
      indicated for femoral trochanteric fracture, however suitable selection of
      fixation method is required depending on fracture type. Any type of surgery
      should be done as fast as possible after fracture as long as general condition of
      the patient is preserved. These surgical treatments for proximal femoral fracture
      will be required more than ever in response to acceleration of aging society in
      Japan.

PMID- 20808048
TI  - [Pharmaceutical treatment for patients with hip fracture].
AB  - It is well known that fracture risk, including second hip fracture, is elevated
      in patients with hip fracture. Therefore, they are good candidate for
      pharmaceutical treatment of osteoporosis to prevent subsequent fractures.
      Nitrogen-containing bisphosphonate is the first line drug for their treatment.
      Teriparatide, which has been recently approved in Japan for the treatment of
      osteoporosis, has osteogenic effects and is expected to prevent fractures in
      patients with hip fracture.

PMID- 20808049
TI  - [Rehabilitation and mobilization in hip fracture patients].
AB  - Exercise program on hip fracture patients is important for recovering from
      functional deficit after operation, and disuse prevention for a maintenance
      phase. Previous reports demonstrated that specific exercise therapy were
      effective in consequence of this fracture patient, but the review showed there
      was not enough evidence in each exercise program. Multidisciplinary
      rehabilitation approach was recommended after hip fracture surgery.

PMID- 20808051
TI  - Serum folate and low-density lipoprotein particle size.
AB  - AIM: Nutritional parameters, such as B-vitamins, have not been studied for an
      association with low-density lipoprotein (LDL) particle size. The present study
      explored whether serum vitamin levels, including folate and vitamin B-12, could
      be associated with LDL particle size. METHODS: Using a randomly selected
      population of 255 hospital workers, we collected detailed lipid profiles,
      including triglyceride (TG), high-density lipoprotein (HDL) cholesterol, and LDL
      particle sizes. The peak particle size of LDL was measured by density gradient
      ultracentrifugation and a pore gradient lipoprotein system. Serum folate and
      vitamin B-12 levels were measured about 1 year later and analyzed. Carotid intima
      media thickness (IMT) and hepatic steatosis were diagnosed ultrasonographically,
      and metabolic syndrome was diagnosed using ATP III criteria. RESULTS: LDL peak
      particle size was significantly correlated with carotid mean IMT (r=-0.16,
      p=0.010). Serum folate levels were significantly and positively correlated with
      HDL cholesterol and negatively with TG, although the latter showed borderline
      significance. With increasing serum folate levels, the LDL peak particle size
      showed a gradual independent increase, even when adjusted for age, sex, hepatic
      steatosis, metabolic syndrome, and the TG/HDL cholesterol ratio. CONCLUSION:
      Folate may act to enhance LDL particle size. Future clinical and research work
      should include a study of the safe application and manipulation of folate levels
      in order to control LDL particle size.

PMID- 20808052
TI  - Impact of having one cardiovascular risk factor on other cardiovascular risk
      factor levels in adolescents.
AB  - AIM: Little is known about the impact of having one cardiovascular (CV) risk
      factor on the levels of other CV risk factors in the general adolescent
      population. We hypothesized that when adolescents have one CV risk factor, the
      levels of other CV risk factors worsen simultaneously. METHODS: Subjects
      consisted of 1,257 healthy adolescent volunteers (549 males and 708 females) aged
      15-18 years. Abdominal obesity, hypertension, raised triglyceride levels,
      decreased HDL-cholesterol levels and hyperglycemia were used as CV risk factors.
      Homeostasis assessment of insulin resistance (HOMA-IR) was used as a surrogate
      marker of insulin resistance. Levels of four biomarkers, leptin, adiponectin,
      high-sensitive C-reactive protein, and desacyl-ghrelin, were also determined. Cut
      offs for gender-specific individual CV risk factor levels were based on the 90th
      (or 10th) percentile values of the subjects in the present study. RESULTS: The
      levels of all CV risk factors and HOMA-IR significantly and simultaneously
      worsened when adolescents had one CV risk factor in both genders. Having any one
      CV risk factor indicated the development of other CV risk factors in adolescents;
      in particular, we found that the development of abdominal obesity in male
      subjects had a harmful effect on the levels of other CV risk factors and was
      associated with the worsening of all four biomarkers examined. CONCLUSIONS: It is
      important to determine the presence or absence of these CV risk factors before
      and/or during adolescence, because having one CV risk factor indicates the start
      of an accumulation of CV risk factors in the general adolescent population.

PMID- 20808053
TI  - Voluntary exercise ameliorates the progression of atherosclerotic lesion
      formation via anti-inflammatory effects in apolipoprotein E-deficient mice.
AB  - AIM: A sedentary lifestyle with insufficient exercise is associated with
      cardiovascular disease. Previous studies have demonstrated that endurance
      exercise benefits atherosclerosis and cardiovascular disorders; however, the
      mechanisms by which physical activity, such as voluntary exercise (Ex), produces
      these effects are not fully understood. METHODS AND RESULTS: Eight-week-old male
      apolipoprotein (ApoE)-deficient mice were fed a standard diet (STD) or high fat
      diet (HFD) for 10 weeks. The HFD+Ex group mice performed Ex on a running wheel
      for 10 weeks. No significant differences in lipid profiles were observed between
      the HFD and HFD+Ex groups. Although changes in body and brown adipose tissue
      weights were comparable between the HFD and HFD+Ex groups, white adipose tissue
      weight was significantly lower in the HFD+Ex group than in the HFD group. The
      areas of atherosclerotic lesions in the aortic sinus and thoracoabdominal aorta
      were significantly reduced in the HFD+Ex group than in the HFD group (p<0.001).
      There was a strong negative correlation between atherosclerotic areas and the
      mean running distance per day in the HFD+Ex group (r=-0.90, p=0.01). Endothelial
      function was significantly preserved in the HFD+Ex group (p<0.05). Serum
      interleukin-6 and macrophage chemoattractant protein-1 levels were significantly
      lower and those of adiponectin were significantly higher in the HFD+Ex group than
      in the HFD group (p<0.05). CONCLUSIONS: These results suggest that Ex ameliorates
      the progression of endothelial dysfunction and atherosclerotic lesion formation
      through anti-inflammatory effects, despite continued consumption of HFD.

PMID- 20808054
TI  - [Purification and characterization of bacterial cytotoxin receptors].

PMID- 20808055
TI  - [Biodiversity and evolution of vibrios].

PMID- 20808056
TI  - [Molecular mechanism of the borrelial proteins at interface with host and vector
      tick interactions].

PMID- 20808057
TI  - [Envelope structure and components of Mycobacterium tuberculosis].

PMID- 20808058
TI  - [Current status and future prospects in a pathogenic study of Vibrio vulnificus].

PMID- 20808059
TI  - The -765C allele of the cyclooxygenase-2 gene as a potential risk factor of
      colorectal cancer: a meta-analysis.
AB  - Colorectal cancer (CRC) is the third leading cause of cancer-related death in the
      world. Human colorectal carcinogenesis is a complex, multistep and multigenetic
      process. Cyclooxygenase-2 (COX2), a key enzyme in arachidonic acid metabolism, is
      overexpressed in several epithelial malignancies including colorectal cancer.
      COX2 expression can be induced by pro-inflammatory and mitogenic stimuli. The 
      765G/C polymorphism of the COX2 gene promoter has been reported to affect CRC
      susceptibility, but recent studies have demonstrated conflicting results. To shed
      light on these inconclusive findings, we performed a meta-analysis for assessing
      the involvement of COX2 -765G/C polymorphisms at the onset of colorectal
      carcinoma. Literature-based searching was guided to gather data and either fixed
      effect or random-effect model was used to pool the odds ratio (OR) according to
      the test of heterogeneity. The 10 eligible case-control studies included 3,322
      colorectal cancer cases and 5,166 controls. Overall, no evidence has indicated
      that individuals carrying GC+CC genotypes had significantly increased colorectal
      cancer risk compared with GG genotype [OR = 1.06, 95% confidence interval (95%
      CI) = 0.94-1.20]. However, stratified analysis with ethnicity indicated that
      individuals carrying GC+CC genotypes had an increased risk of colorectal cancer
      (OR = 1.40, 95% CI = 1.11-1.76) among Asian population. In conclusion, although
      not all bias could be eliminated, the -765C allele of the COX2 gene may be a
      potential risk factor for colorectal cancer in Asians.

PMID- 20808060
TI  - [An effective method to shorten the learning curve of HoLEP].
AB  - Holmium laser enucleation of the prostate (HoLEP) is a safe and effective
      treatment for patients with symptomatic benign prostatic hyperplasia (BPH), but
      is a difficult operation. To shorten the learning curve, we evaluated the
      surgical outcome of successive bilateral lobe enucleations with HoLEP. Performed
      by an inexperienced endourologist and an expert. Between March and July on 2009,
      we evaluated 20 cases of HoLEP performed by a beginner who underwent successive
      bilateral lobe enucleations and 20 cases of HoLEP performed by an expert.
      Enucleation time was shortened when successive bilateral lobe enucleations were
      performed by the beginner using HoLEP (115 vs 92 minutes, p<0.05). The
      enucleation time was significantly shorter in the expert group than in the
      beginner group. However, there were no significant differences in morcellation
      time, enucleated tissue weight, hemoglobin decrease level, sodium decrease level,
      catheterization time or significant incontinence time between the two groups. The
      postoperative evaluations was excellent in both groups. We conclude that HoLEP is
      a safe and effective operation. However, close supervision by an expert is
      required. In addition, learning from the easier part of enucleation to elaborate
      skill sets required to perform HoLEP is prerequisite for success.

PMID- 20808061
TI  - [Giant solitary fibrous tumor of a kidney: a case report].
AB  - Renal solitary fibrous tumor (SFT) has been reported infrequently. We report a
      case in a 39-year-old woman with a 9-month history of sense of abdominal
      fullness. Computed tomography revealed well-encapsulated heterogeneous tumors
      involving the lower pole of the left kidney with left renal vein extension. The
      tumors measured approximately 20 cm in diameter and displaced adjacent organs. We
      performed preoperative transcatheter arterial embolization of the left renal
      artery. Left nephrectomy with complete tumor resection was achieved without major
      complications. The tumors were well-circumscribed and composed of spindle cells
      in a collagenous stroma. Immunohistochemistry showed reactivity for CD34 and bcl
      2. Immunohistochemical stains for c-kit and CD10 were negative. A diagnosis of
      SFT was made based on light microscopy and immunohistochemistry. The patient is
      alive with no evidence of disease 6 months after the operation. This case is the
      largest renal SFT in the Japanese literature.

PMID- 20808062
TI  - [A case report of urinary extravasation by renal trauma Grade III successfully
      managed by percutaneous drainage].
AB  - A 30-year-old man was diagnosed with renal trauma Grade a and hospitalized on
      February 22, 2009. There was no apparent stenosis from the renal pelvis to ureter
      on pyelography, but computed tomography demonstrated urinary extravasation on
      March 2. An indwelling drainage catheter was placed percutaneously by an
      ultrasound-guided approach. An incidental ureter-obstructing blood clot prolonged
      the indwelling period of the drainage catheter, but we succeeded in avoiding open
      surgery. Although ureteral stenting might be generally selected for the primary
      management of traumatic urinary extravasation, it should be remembered that
      percutaneous drainage is effective in some cases. We consider it important to
      select the optimal treatment based on an accurate diagnosis of each case.

PMID- 20808063
TI  - [A case of Candida parapsilosis fungal balls in the urinary tract associated with
      a retrocaval ureter].
AB  - A 70-year-old man with a medical history of diabetes mellitus presented to a
      local clinic with seven days history of right flank pain and fever. Because there
      was no symptomatic improvement after one-week antibiotic administration,
      abdominal ultrasonography and computed tomographic scans were performed to show
      mass lesions in the right hydropelvis, and he was transferred to our hospital.
      Retrograde pyelography revealed a retrocaval ureter and a ureteral stent was
      indwelt. After the symptoms improved, the lesions were removed by percutaneous
      nephrostomy and fungal balls were diagnosed as Candida parapsilosis after
      culture. After intermittent one-week irrigation of the renal pelvis with normal
      saline, the nephrostomy tube was removed. In six-month follow-up, mild
      hydronephrosis remains without fungal ball recurrence. To the best our knowledge,
      there has been no case report of Candida parapsilosis fungal balls in the urinary
      tract.

PMID- 20808064
TI  - [A case of urachal carcinoma treated with S-1/CDDP combination chemotherapy].
AB  - No established treatment exists for urachal carcinoma,except curative
      resection,and its prognosis is poor. More than 80% of urachal carcinomas are
      adenocarcinomas. We report a case of advanced urachal carcinoma treated with S-1
      and cisplatin combination (S-1/CDDP) chemotherapy. The patient,a 61-year-old
      woman,presented with macroscopic hematuria. A tumor was detected on the bladder
      dome and transurethral resection was performed. Histopathological findings
      indicated poorly differentiated adenocarcinoma. Serum carcinoembryonic antigen
      and carbohydrate antigen 19-9 levels were 3.5 ng/ml and 140 U/ml respectively.
      Magnetic resonance images indicated an extension of this tumor to the
      retroperioneal space. Metastasis to her right ischium was suspected from bone
      scintigraphy results. The tumor was diagnosed as stage IVB (Sheldon's category)
      urachal carcinoma. After one cycle of S-1/CDDP chemotherapy,the size of the tumor
      on the bladder dome decreased,after which total cystectomy was performed. The
      surgical margin of the cystectomy specimen was negative for malignant
      cells,although poorly differentiated adenocarcinoma was still observed in this
      specimen. The findings of this study indicate that this therapy might be
      beneficial for treating advanced urachal carcinomas. This is the second report of
      successful treatment of advanced urachal carcinoma with S-1/CDDP chemotherapy.

PMID- 20808065
TI  - [Septic shock due to fluoroquinolone-resistant Escherichia coli after trans
      rectal prostate needle biopsy].
AB  - A 64-year-old man took levofloxacin 100 mg three times a day from the day before
      trans-rectal prostate needle biopsy. He suddenly fell into septic shock about 12
      hours after the biopsy. We performed polymyxin B-immobilized fiber-direct
      hemoperfusion treatment at our intensive care unit. The circle dynamics was
      stable after five days of observation, and he was discharged seven days after the
      event. Levofloxacin-resistant Escherichia coli (E. coli) was detected by blood
      and urine culture.

PMID- 20808066
TI  - [A case of lymphangioma of the intrascrotum in an adult].
AB  - We reported a rare case of intrascrotal lymphangioma in an adult. A 31-year-old
      man visited a urological clinic with a chief complaint of left scrotal swelling
      since a few days ago, and was pointed out to have a left intrascrotal cystic
      mass. The patient was sent to our hospital for further examination in 23 April
      2008. The left scrotal mass was palpated elastic hard below the left testis and
      its surface was irregular. Light transillumination test showed positive.
      Ultrasonography revealed a cystic mass 7.0 x 4.4 x 4.5 cm with multiseptate
      accumulation at the lower pole of the left testis. Magnetic resonance imaging
      showed low intensity by T1WI and high intensity by T2WI, suggesting a protein
      rich component. We suspected left intrascrotal lymphangioma and extirpated the
      scrotal mass under lumbar anesthesia. Pathological examination demonstrated
      lymphangioma. The patient had no evidence of recurrence after 1 year.

PMID- 20808067
TI  - [A case of labial adhesion in a reproductive woman].
AB  - A 21-year-old woman was admitted to our hospital with a complaint of voiding
      difficulty and urinary retention. On examination, the labia was found to be
      extensively fused with a pinhole opening in the center of adhesion from which
      urine discharged. The fusion was separated surginally under the diagnosis of
      labial adhesion. Labial adhesions generally occur in children or post-menopausal
      women, but are extremely rare in reproductive women. This is the sixth case of
      labial adhesion in a reproductive woman reported in Japan.

PMID- 20808068
TI  - [Marginal - donor and recipient].
AB  - A significant gap exists between organ supply and demand in the world. Marginal
      donors have been accepted as organ donors in recent years. On the other hand,
      aging recipients and recipients with complications have increased. This symposium
      was organized to discuss marginal donors and high risk recipients. We discussed
      fundamental researches such as prevention of renal ischemia reperfusion injury by
      erythropoitin and hepatocyte growth factor-macrophage stimulating protein (HGF
      MSP) chimera, and the acquired tolerance induction using the CD28 superagonist
      antibody. We believe that this discussion will help increase the number of
      cadaveric kidney transplantations and improve the treatment outcome.

PMID- 20808069
TI  - [Marginal donor and high risk recipient in kidney transplantation].
AB  - With the current shortage of solid organs for transplant, the transplant
      community continues to look for ways to increase the number of organ donors,
      including marginal donors. In Japan, deceased organ donation is limited and ABO
      incompatible kidney transplantation has flourished since the 1990's. Recently,
      older donors have been increasing in kidney transplantation. There has also been
      an increase of older recipients and high-risk recipients such as highly
      sensitized recipient is recognized. We review the evaluation and management for
      the marginal donor and high-risk recipient.

PMID- 20808070
TI  - [Renal protective effects of erythropoietin on ischemic reperfusion injury].
AB  - We reexamined the conditions of tissue disorders resulting from temporary
      ischemia of the organs as well as changes in tissue function and the effects on
      the preservation of renal function over time by using rat models in order to
      clinically utilize erythropoietin, which has inhibitory effects on ischemia
      reperfusion disorders. In 8- to 9-week-old Wister male rats, after the right
      kidney had been resected under general anesthesia, the left renal artery was
      clamped to inhibit the blood flow for 45 minutes. At 30 minutes before inhibiting
      the blood flow and after releasing the inhibited blood flow, 100 U/kg of
      recombinant human erythropoietin (rhEPO) was administered via the inferior vena
      cava and the abdominal cavity, and then the tissues and blood samples were
      extracted at 6 hours and 24 hours after the release. The renal tissue specimens
      were evaluated for apoptosis and renal function using hematoxylin eosin staining
      and TUNEL staining. Changes in the emergence of active oxygen were investigated
      by using blood samples. The degree of renal dysfunction was evaluated by
      measuring neutrophil gelatinase-associated lipocalin (NGAL) in the spot urine
      samples. The changes in the serum creatinine level, showed that the renal
      function was preserved with a significant difference in the rhEPO administration
      group. The liver deviation enzymes clearly decreased in the rhEPO administration
      group. Active oxygen did not change before and after the ischemia-reperfusion nor
      was it changed by rhEPO administration. Apoptosis was inhibited by rhEPO
      administration. No direct effects of rhEPO administration on the emergence of
      active oxygen were observed. The administration of rhEPO, was suggested to help
      preserve the renal function in marginal donors with a longer agonal stageby
      effectively.

PMID- 20808071
TI  - [Kidney transplantation: how shall we deal with marginal cases? Future prospects
      from basic research].
AB  - The research performed at the Department of Urology Osaka University Graduate
      School of Medicine is overviewed. Renal ischemia-reperfusion (I/R) injury is
      inevitable in transplantation and is related to longterm graft function. MF-1, a
      bifunctional hepatocyte growth factor-macrophage stimulating protein chimera, was
      found to prevent apoptosis. In our study, MF-1 directly guarded cultured proximal
      tubular epithelial cells from hypoxia-induced necrosis and apoptosis in vitro,
      and MF-1 treatment ameliorated renal dysfunction by preventing apoptosis in rat
      I/R injury model. The erythropoietin molecule modified by carbamylation (CEPO)
      has been identified and was demonstrated to protect several organs without
      increasing the hemoglobin concentration. The therapeutic effect of CEPO was
      evaluated using an endothelial tube formation assay, and a rat ischemia
      reperfusion injury model. CEPO treatment induced more capillarylike formation
      than EPO. CEPO-treated kidneys showed minimal tubular apoptosis with increased
      peritubular capillary endothelial cells. We identified a new therapeutic approach
      using CEPO to protect the kidney from ischemia-reperfusion injury by promoting
      angiogenesis.

PMID- 20808073
TI  - Age-related bone mineral density, osteoporosis rate and risk of vertebral
      fracture in mainland Chinese women with type 2 diabetes mellitus.
AB  - Few data are available regarding bone mineral density (BMD) and the risk of
      vertebral fracture among mainland Chinese women with type 2 diabetes mellitus
      (T2DM). A decrease in the bone projective area (BPA) can be an indirect marker
      reflecting compressed vertebral fracture. We investigated age-related BMD, BPA,
      and the prevalence of osteoporosis in women with T2DM in mainland China. BMD and
      BPA of the posteroanterior lumbar spine (L1-L4) and hip were measured by dual
      energy X-ray absorptiometry in 1253 women with T2DM and 1194 control subjects
      without diabetes aged 40-80 yr. BMD of the lumbar spine and hip decreased with
      age. BMD of the lumbar spine was higher in T2DM than controls (p<0.05-0.001), as
      was BPA at some vertebral bodies (p<0.05-0.001), whereas no significant
      intergroup differences in BPA were observed at the hip. The prevalence of
      osteoporosis in the women with T2DM increased with age: 0-2.58% at age 40-49 yr,
      6.94-28.4% at age 50-59 yr, 32.7-76.7% at age 70-80 yr, with the range reflecting
      differences between skeletal sites. In subjects over 60 yr, the rates of
      osteoporosis at posteroanterior spine were significantly lower in T2DM patients
      than in controls (p<0.05-0.001). In conclusion, women with T2DM had higher BMD
      and lower risk of osteoporosis. Higher BPA of the vertebrae indicated that women
      with T2DM in mainland China would have a lower risk of vertebral fracture than
      non-diabetic women.

PMID- 20808072
TI  - Effects of low- and high-intensity exercise training on body composition and
      substrate metabolism in obese adolescents.
AB  - The objective was to investigate the effects of a 3- week weight-management
      program including moderate energy restriction and exercise training at 2
      intensities [low intensity (LI): 40% and high intensity (HI): 70% maximal oxygen
      uptake (V'O(2)max)] on body composition, energy expenditure, and fat oxidation
      rate in severely obese adolescents. Twenty obese adolescents, aged 15-17 yr (body
      mass index: 37.5 kg/m(2); 38.2% fat mass) participated in this study. Before
      starting (week 0, W0) and at the end of the weight-management period (week 3,W3),
      body composition was assessed by a multifrequency tetrapolar impedancemeter;
      basal metabolic rate (BMR), energy expenditure, and substrate oxidation rate
      during exercise and post-exercise recovery by indirect calorimetry. At W3, body
      mass and fat mass decreased significantly (p<0.005) in all groups, and the
      decreases were significantly greater in the LI than in the HI group (-8.1+/-1.6
      vs -5.9+/-1.6 kg and -4.2+/-1.9 vs -2.3+/-1.7 kg, p<0.05, respectively).
      Predicted V'O(2)max, expressed in relative values, changed significantly only in
      the HI group by +0.010+/-0.006 l/(kg fat-free mass * min) (p=0.010). By contrast,
      no significant changes were observed at W3 in BMR, energy expenditure, and
      substrate oxidation rate during exercise and post-exercise recovery. In
      conclusion, LI (40% of V'O(2)max) physical activity favors fat oxidation and it
      seems advisable to encourage obese adolescents to perform LI physical activity
      which is more feasible and acceptable than intense exercise.

PMID- 20808074
TI  - Alterations in arterial pressure in patients with Type 1 diabetes are associated
      with long-term poor metabolic control and a more atherogenic lipid profile.
AB  - AIM: To determine the prevalence of alterations in blood pressure (BP) in
      patients with Type 1 diabetes who are normoalbuminuric and normotensive; and to
      evaluate the association with genetic, clinical and metabolic factors. MATERIAL/
      METHODS: Normoalbuminuric, normotensive Type 1 diabetic patients (no.=85) had
      their ambulatory blood pressure monitoring (ABPM) performed over 24 h, together
      with measurement of HbA1c and lipid profile, polymorphisms of the ACE gene, non
      midriatic retinography, and the "historical HbA1c" calculated (mean of all the
      determinations available on the patient). RESULTS: Of the 85 patients, a mean of
      18.8% had pathologic values of BP over the 24 h, 31.8% during active periods and
      22.4% during rest periods; in 42% there was a non-dipper pattern in BP. The
      patients with alterations of BP had higher body mass index (BMI), higher levels
      of glycemia and of triglycerides, and decreased levels of HDL cholesterol. The
      "historical HbA1c" was significantly higher in the patients with the non-dipper
      pattern (8.6 +/- 1.4% vs 7.9 +/- 1.4%; p=0.046). Pulse pressure was directly
      associated with male gender (p=0.006) and with BMI (p=0.001). No differences were
      detected in the distribution of the polymorphisms of the ACE gene as a function
      of the BP alterations. CONCLUSIONS: An elevated number normoalbuminuric,
      normotensive, Type 1 diabetic patients have alterations in BP detected with ABPM
      over 24 h, and these are associated with a greater BMI, poor long-term metabolic
      control and a more atherogenic lipid profile.

PMID- 20808075
TI  - Influences of mutuality, preparedness, and balance on caregivers of patients with
      dementia.
AB  - BACKGROUND: There is a lack of research exploring the influence of the role
      implementation process of family caregivers of older people with dementia in
      Taiwan. PURPOSE: The purpose of this study was to investigate the predictive
      ability on positive and negative caregiving outcomes of several role
      implementation variables, including mutuality, preparedness, and balance between
      competing needs. METHODS: A cross-sectional, correlational study design was used.
      Data were collected from family caregivers of patients with dementia from
      neurological clinics at a medical center and at local hospitals through a take
      home mail survey. One hundred seventy-six family caregivers of patients with
      dementia completed the Family Caregiving Inventory. RESULTS: After controlling
      for age and gender of the family caregiver and the cognitive function of the
      elderly patients, mutuality was found to associate negatively with role strain
      and depressive symptoms and positively with rewards and mental health. Higher
      preparedness was associated with higher caregiving rewards and better mental
      health. Less balance was associated with more severe depressive symptoms and
      poorer mental health. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Greater attention,
      support, and consultation should be directed at caregivers with low mutuality,
      less preparedness, and less balance between competing needs. Specifically, family
      caregivers with low mutuality are at risk of higher role strain and more
      depressive symptoms. Those in such a category should be identified and should
      receive intervention as early as possible. Interventions to enhance family
      caregiver preparedness should be developed to increase caregiving rewards and to
      improve caregiver mental health.

PMID- 20808076
TI  - Managing problem behaviors in cognitively impaired older people: the competence
      and preparedness of healthcare providers in long-term care facilities.
AB  - BACKGROUND: The prevelance of cognitive impairment in older individuals is
      increasing in Taiwan. Most healthcare providers (HCPs) experience deep
      frustration while caring for residents of long-term care facilities who are
      cognitively impaired. Competence and preparedness of HCPs represent key factors
      in being able to successfully create and maintain a safe environment for elderly
      wards and are one of the main concerns of cognitive impairment care. PURPOSE: The
      purpose of this study was to investigate the competence and preparedness of HCPs
      to manage the problem behaviors of cognitively impaired elders living in long
      term care facilities. METHODS: This study utilized a correlational research
      design and included 221 participants that were recruited using a stratified
      random sampling process. Structured and semistructured questionaires on
      competence and preparedness of caring for cognitively impaired elders were used
      to collect data. Descriptive statistics and univariate and multivariate analyses
      were used to analyze the relationship between HCP demographic characteristics and
      their competence or preparedness in managing cognitive impairment care. RESULTS:
      Ninety-five percent of participants were women. The top scoring item in the
      competence dimension was "preventing problem behaviors from occurring" (M +/- SD
      = 3.89 +/- 2.89), and the lowest scoring item was "reading related books and
      articles" (2.91 +/- 0.85). In the preparedness dimension, "modification of
      environment" (3.22 +/- 1.07) was the highest scoring item, and "resources
      referral skills" was the lowest scoring item (3.02 +/- 1.03). Results showed
      supervisors (F = 7.89, p = .001) and college graduates (F = 2.89, p = .047) to
      have higher levels of competency than other participants. Participant knowledge
      level in dealing with problem behaviors was significantly and positively
      correlated with frequency of continuing education participation (F = 28.73, p <
      .001). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Results point to the need for
      continuing education, practicum, counseling, staffing resources, and involvement
      of other professionals to increase HCP readiness and competence.

PMID- 20808077
TI  - The use of music intervention in healthcare research: a narrative review of the
      literature.
AB  - BACKGROUND: Although music has been widely used in healthcare, there has been
      scant review of literature analyzing the use of music as an intervention in
      healthcare research. PURPOSE: The purpose of this article was to provide a
      narrative review of the literature to explore how "music therapy" has been used
      in healthcare research to promote healing in adult populations. The following
      five questions were addressed: (a) In what populations and under what conditions
      has music intervention been studied? (b) What specific kinds of music have been
      used for study intervention? (c) How has the music intervention been
      operationalized? (d) What metrics have been used as outcome measures? (e) Have
      music interventions been effective? METHODS: Articles were retrieved from several
      scientific databases (PubMed, CINAHL, and PsycINFO) using the following search
      parameters: MeSH search terms "music therapy" in the title field with the search
      limit to "adults 19 years and older," "humans," "clinical randomized controlled
      studies," and "English." A total of 33 clinical randomized controlled studies
      that met the search criteria were reviewed. RESULTS: (a) In the reviewed studies
      (studied articles), subjects with dementia were the most commonly studied
      population group, and the predominant aim of the study was to alleviate anxiety.
      (b) Employed music interventions may be categorized as one of two types: passive
      (receptive) and active. The passive (receptive) music intervention commonly
      involved subjects in a resting position listening to music, whereas the active
      music intervention is usually carried out in a group format in which subjects are
      actively involved in the music intervention. (c) Intervention frequency, dosing,
      and duration were highly variable across the reviewed studies. Very few studies
      described the intervention setting, which made evaluation of these studies
      difficult. Direct supervision seemed to be an influential factor for adherence.
      (d) Outcome measures in retrieved articles involved two types: psychological and
      physiological or biological. (e) The effectiveness of music intervention was
      reported as successful in most of the retrieved studies. CONCLUSION: Much work
      has been done on the use of music interventions in the clinical setting. Future
      research should consider participant music selection preferences, and the
      selection of active versus passive intervention approach should be based on a
      clear conceptual framework. Combining both physiological and psychological
      measures in the study design is a recommended approach to increase measurement
      validity.

PMID- 20808078
TI  - Comparison of health-promoting lifestyles between postnatal han taiwanese and
      indigenous women.
AB  - BACKGROUND: The health-promoting lifestyle of postpartum women is an important
      issue, but few studies have been undertaken to examine the role of cultural
      difference. PURPOSE: The purpose of this study was to better understand the
      health-promoting lifestyles of postnatal mothers in Taiwan in terms of
      differences between ethnic Han Taiwanese and indigenous women and of factors
      predicting health-promoting lifestyles in the two groups. METHODS: For this cross
      sectional comparative study, data on postnatal health-promoting behaviors, as
      measured using the Health-Promoting Lifestyle Profile (HPLP), were collected from
      314 mothers during their sixth postpartum week. HPLP scores of ethnic Han
      Taiwanese mothers living in Kaohsiung City, and indigenous women living in
      Pingtung County were then compared. RESULTS: : Han Taiwanese and indigenous
      mothers differed significantly in terms of age, education, employment status,
      socioeconomic status, type of family, and primary postnatal helper. Han Taiwanese
      had better original scores in overall health-promoting lifestyle, self
      actualization, stress management, nutrition, and interpersonal support. However,
      these differences did not achieve statistical significance when subjected to
      analysis of covariance. Indigenous participants had significantly higher scores
      in terms of health responsibility and exercise than Han Taiwanese women.
      Significant predictors of higher HPLP score in the Han Taiwanese group included
      employment status and breast-feeding, which together accounted for 8.2% of total
      variance. In the indigenous group, significant predictors of higher HPLP score
      included more years of education and middle socioeconomic status, which together
      accounted for 22.0% of total variance. CONCLUSIONS/IMPLICATIONS FOR PRACTICE:
      Results showed significant differences in the health responsibility and exercise
      subscales and significant differences in key predictors between the Han Taiwanese
      and the indigenous groups. Findings support the role of culture as a significant
      factor affecting the health-promoting lifestyle of postnatal women in Taiwan.
      Nurses should be aware of cultural mores and influences when delivering
      healthcare to postpartum mothers of different ethnic groups to maximize postnatal
      care efficacy.

PMID- 20808079
TI  - Use of medication by nursing home residents nearing end of life: a preliminary
      report.
AB  - BACKGROUND: Nursing home residents usually suffer from a variety of medical
      conditions and are prescribed a wider variety of medications than any other
      subpopulation. Polypharmacy is associated with the occurrence of adverse events.
      PURPOSE: The purposes of this study were to describe the medication prescription
      patterns of residents who died in a nursing home, to examine how this pattern
      changed as residents progressed toward death, and to identify correlates of
      increased medication prescriptions. METHODS: Thirty-one residents who had lived
      at one nursing home for more than 6 months before death were included in the
      study. Medication records for participants were obtained at four data collection
      points: on admission, 6 months before death, 3 months before death, and at death.
      RESULTS: The mean number of medications prescribed immediately before death was
      7.90 (SD = 3.27), and there was an upward trend in number of prescriptions
      written as patients neared death. The most frequent prescription was for
      medication for constipation, pulmonary care, and hypertension. There was a
      significant correlation between residents with heart disease and increased
      medication use. Medication prescribed for pulmonary care and hypertension
      increased from admission to death, but a decreased use of medication for pain
      relief in the time before death in these cases was found.
      CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study surveyed and described the
      pattern of medication use in nursing home residents from admission to the end of
      life. Results can be used to reinforce clinician and nursing staff awareness of
      prescription frequency, amounts of medication, and change over time for elderly
      residents under their care. In addition to safer prescribing practices for the
      older people, nonpharmacological strategies (e.g., lifestyle modification and
      physiotherapy for function training) may be used to address common symptoms and
      complaints during chronic care.

PMID- 20808080
TI  - Validation of the braden self-help model in women with systemic lupus
      erythematosus.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease that
      requires lifelong follow-up treatment. Most SLE patients experience feelings of
      helplessness and frustration in the period after which the condition has been
      brought under control but not yet cured. Thus, to improve the SLE patient's
      quality of life (QOL), it is very important to assist them to adjust to face both
      the severity of their disease and their own feelings of limitation and
      uncertainty, to understand their condition and required treatments, and to adopt
      self-help strategies to adjust to difficulties in daily life. PURPOSE: This study
      was designed to test both the hypothesized relationships in the Braden Self-help
      Model and the mediating effects of self-help on QOL in a sample of women with
      SLE. DESIGN/METHODS: A cross-sectional design with causal modeling approach was
      used to verify specified relationships in the theoretical model. SLE patients who
      were registered with the Rainbow SLE Association and the Lupus SLE Foundation in
      Taiwan were recruited as participants by convenience sampling. A total of 231 SLE
      patients participated in this project. Data were collected using a self
      administered structured questionnaire consisting of a personal information
      section, the Disease Course Graphic Scale, the Mishel Uncertainty in Illness
      Scale, the Limitation Scale, the Self-Control Scale, the Adult Role and Behavior
      Scale, and the Well-Being Scale. RESULTS: Path analysis found a high level of
      significance for the coefficient of each path. We also identified a positive
      correlation between the disease severity and limitations and the factor of
      uncertainty and a negative correlation between the limitations and uncertainty
      and the factors of enabling skills, self-help, and QOL. A positive correlation
      among enabling skills, self-help, and QOL was also evident. The Sobel analysis
      pointed to self-help as having the greatest impact on QOL (79.15%).
      CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The study examined the applicability of
      the causal Braden Self-help Model on women with SLE and provides a basis for the
      design of intervention activities.

PMID- 20808081
TI  - Effectiveness of informational and emotional consultation on the psychological
      impact on women with breast cancer who underwent modified radical mastectomy.
AB  - BACKGROUND: Female breast cancer has been ranked as the leading cause of cancer
      death in Taiwan. Women who undergo a mastectomy are at risk of suffering
      emotional disturbance because of deteriorating body image. A nursing intervention
      designed to restore body image perceptions and to reduce anxiety and emotional
      distress in this vulnerable group should be developed and administered. PURPOSE:
      This study was developed to evaluate the effectiveness of informational and
      emotional consultation on body image, anxiety, and emotional distress in women
      with breast cancer who underwent modified radical mastectomy. METHODS: A quasi
      experimental design with convenience sampling was used. Two hospitals within the
      same hospital system in southern Taiwan provided the research setting. Sixty
      three women diagnosed with breast cancer completed the interviews (experimental
      group = 32, control group = 31). The experimental group participants received a
      two-session informational and emotional consultation, whereas those in the
      control group received routine nursing care only. All participants completed a
      series of three face-to-face interviews, including one pretest (Time 1, before
      surgery), a first posttest (Time 2, the day of discharge), and a second (follow
      up) test (Time 3, 2 months after surgery). RESULTS: The intervention had an
      immediate positive effect (i.e., on the day of hospital discharge) on anxiety and
      a delayed positive effect (i.e., 2 months after surgery) on body image, anxiety,
      and emotional distress. The experimental group participants indicated a high
      level of satisfaction with the intervention. CONCLUSIONS/IMPLICATIONS FOR
      PRACTICE: Our findings suggest the ability of this nursing informational and
      emotional consultation intervention to reduce patient anxiety at both short- and
      long-term stages. However, improved perception of body image and emotional
      distress only over the longer term indicates that these dimensions take time to
      be internalized and improved. This nursing informational and emotional
      consultation intervention may provide a guide for hospitals and nurses in caring
      for women recovering from modified radical mastectomy surgery.

PMID- 20808082
TI  - Analysis of factors found to affect self-perceived weight status in australia.
AB  - BACKGROUND: Obesity and being overweight are two of the most important emerging
      public health issues in our time and regarded by the World Health Organization
      (1998) as a worldwide epidemic. The prevalence of obesity is greatest in the
      United States followed by Australia. PURPOSE: This study examined potential
      associations between sociodemographic factors, physical activity and dietary
      habits, and self-perception of being overweight in Australian adults and proposed
      a range of health promotion strategies. METHODS: The three most recent Australian
      National Health Survey databases (1995, 2001, and 2004/2005) were used as primary
      data sources. A total of 74,114 Australian adults aged 20 years and older were
      recruited from these databases. RESULTS: After controlling for other factors,
      people in the 2001 and 2005 databases were significantly less likely to self
      perceive themselves as overweight than those in the 1995 database (p < .01).
      Females, younger people, English speakers, and individuals who were married with
      child/children were more likely to self-perceive themselves as overweight. In
      exercise, people who did less exercise were more likely to self-perceive
      themselves to be overweight than those who engaged in regular, strenuous
      exercise. CONCLUSIONS: Health promotion and education activities should provide
      education on general public health and education targeted to the needs of
      specific at risk subgroups. Also, further research into this topic should be
      longitudinal and designed to examine the causal relationship between being
      overweight and/or obesity and self-perceptions regarding body weight status.

PMID- 20808083
TI  - Cognitive control in late-life depression: response inhibition deficits and
      dysfunction of the anterior cingulate cortex.
AB  - OBJECTIVES: Geriatric depression is associated with frontolimbic functional
      deficits, and this frontal dysfunction may underlie the marked executive control
      deficits often seen in this population. The authors' goal was to assess the
      integrity of frontal cortical functioning in geriatric depression, while these
      individuals performed a standard cognitive control task. The N2 component of the
      event-related potential (ERP), an evoked response generated within the anterior
      cingulate cortex (ACC), is significantly enhanced when nondepressed individuals
      successfully inhibit a response, providing an excellent metric of frontal
      inhibitory function. DESIGN: The authors used a variant of a demanding Go/NoGo
      task-switching paradigm that required participants to inhibit response execution
      during NoGo trials by overcoming a potent response tendency established by
      frequent Go trials. PARTICIPANTS: The authors compared a cohort of depressed
      geriatric outpatients (N = 11) with a similarly aged group of nondepressed
      participants (N = 11). MEASUREMENTS: Reaction times, accuracy, and high-density
      event-related potential recordings from a 64-channel electrode montage were
      obtained. RESULTS: A significantly enhanced N2 to NoGo trials was observed in
      nondepressed elderly participants, with generators localized to the ACC. In
      contrast, this enhancement was strongly reduced in the depressed sample. Source
      analysis and topographic mapping pointed to a displacement of N2 generators
      toward more posterior areas of the middle frontal gyrus in depressed subjects.
      CONCLUSIONS: Findings confirm previous reports of an inhibitory control deficit
      in depressed elderly who show significantly increased rates of commission errors
      (i.e., failures to inhibit responses on NoGo trials). Electrophysiologic data
      suggest underlying dysfunction in ACC as the basis for this deficit.

PMID- 20808084
TI  - Depressive symptoms are associated with subclinical cerebrovascular disease among
      healthy older women, not men.
AB  - BACKGROUND: Associations among diagnosed unipolar depression, depressive
      symptoms, and cerebrovascular disease are well known. However, minimal research
      has investigated whether sex may modify such associations, despite known sex
      differences in depression and depressive symptoms. This study examined whether
      depressive symptoms were disproportionately related to subclinical
      cerebrovascular disease (SCD) in women versus men. METHODS: One hundred one older
      adults (58% men; mean age = 67 years), free of major comorbidities, completed the
      Beck Depression Inventory and underwent magnetic resonance imaging (MRI). MRI
      scans were neuroradiologist rated for markers of SCD (periventricular and deep
      white matter hyperintensities, and number of silent infarcts) and brain atrophy
      (ventricular enlargement and sulcal widening). Two rank-sum outcome variables
      (SCD and brain atrophy) were then created. RESULTS: On average, depressive
      symptoms were relatively low in magnitude (mean = 3.8, standard deviation = 3.6,
      range = 0-17). Multiple regression analyses, adjusted for age, sex, education,
      systolic blood pressure, fasting glucose, maximal oxygen consumption, body mass
      index, average weekly alcohol consumption, and Mini-Mental State Examination
      performance revealed sex to be a significant effect modifier of depressive
      symptoms in the prediction of SCD. Sex-stratified regression analyses indicated
      depressive symptoms, and SCD was strongly related among women but not men.
      Depressive symptoms were not related to brain atrophy, regardless of inclusion of
      sex as an effect modifier. CONCLUSIONS: Depressive symptoms, even in a
      subclinical range, are significantly associated with an MRI-derived index of SCD
      among women, but not men, in the present sample of relatively healthy older
      adults.

PMID- 20808085
TI  - Depression-executive dysfunction syndrome relates to poor poststroke survival.
AB  - BACKGROUND: The aim of this study was to investigate the influence of poststroke
      depression and executive dysfunction on long-term survival after acute stroke.
      METHODS: A total of 257 consecutive acute ischemic stroke patients were included
      in the study and followed up to 12 years. Depression was diagnosed 3 months after
      stroke in 99 patients (38.5%). FINDINGS: In Kaplan-Meier analysis, there was no
      difference in survival of patients with and without poststroke depression (8.7
      versus 8.3 years). Instead, patients with both depression and executive
      dysfunction had shorter median survival than patients with neither depression nor
      executive dysfunction (6.6 versus 10.3 years). Comparison between all patients
      with executive dysfunction and patients without it, not regarding depressive
      status, showed that executive dysfunction in itself was strongly associated with
      poor poststroke survival (6.4 versus 10.6 years). In stepwise Cox regression
      proportional hazards analysis adjusted with covariates, poststroke depression
      with executive dysfunction (hazard ratio [HR] 1.63) and advanced age (HR 1.11)
      remained as independent predictors of poor long-term survival. INTERPRETATION:
      The authors' well-defined poststroke cohort with long-term follow-up indicates
      that in poststroke depression, the depression-executive dysfunction syndrome is
      the predictor of poor long-term survival rather than depression in itself.

PMID- 20808086
TI  - Neuropsychiatric symptoms and syndromes in a large cohort of newly diagnosed,
      untreated patients with Alzheimer disease.
AB  - OBJECTIVES: Neuropsychiatric symptoms are common in patients with Alzheimer
      disease (AD). Treatment for both AD and psychiatric disturbances may affect the
      clinical observed pattern and comorbidity. The authors aimed to identify whether
      particular neuropsychiatric syndromes occur in untreated patients with AD,
      establish the severity of syndromes, and investigate the relationship between
      specific neuropsychiatric syndromes and AD disease severity. DESIGN: Cross
      sectional, multicenter, clinical study. PARTICIPANTS: A total of 1,015 newly
      diagnosed, untreated outpatients with AD from five Italian memory clinics were
      consecutively enrolled in the study from January 2003 to December 2005.
      MEASUREMENTS: All patients underwent thorough examination by clinical
      neurologists/geriatricians, including neuropsychiatric symptom evaluation with
      the Neuropsychiatric Inventory. RESULTS: Factor analysis revealed five distinct
      neuropsychiatric syndromes: the apathetic syndrome (as unique syndrome) was the
      most frequent, followed by affective syndrome (anxiety and depression),
      psychomotor (agitation, irritability, and aberrant motor behavior), psychotic
      (delusions and hallucinations), and manic (disinhibition and euphoria) syndromes.
      More than three quarters of patients with AD presented with one or more of the
      syndromes (N = 790, 77.8%), and more than half exhibited clinically significant
      severity of symptoms (N = 603, 59.4%). With the exception of the affective one,
      all syndromes showed an increased occurrence with increasing severity of
      dementia. CONCLUSIONS: The authors' study supports the use of a syndrome approach
      for neuropsychiatric evaluation in patients with AD. Individual neuropsychiatric
      symptoms can be reclassified into five distinct psychiatric syndromes. Clinicians
      should incorporate a thorough psychiatric and neurologic examination of patients
      with AD and consider therapeutic strategies that focus on psychiatric syndromes,
      rather than specific individual symptoms.

PMID- 20808087
TI  - Plasma homocysteine levels and major depressive disorders in Alzheimer disease.
AB  - BACKGROUND: The main aim of this study was to examine the symptomatology of major
      depression in Alzheimer disease (AD) and its relationship with plasma
      homocysteine level. METHODS: Eighty-three patients with AD were enrolled for
      clinical assessments and examination of fasting plasma homocysteine. Diagnosis of
      major depression was made, and the severity of the depression was assessed.
      RESULTS: The moderate dementia patients presented with more common behavioral
      disturbances related to major depression than mild dementia patients. Major
      depression in patients with moderate AD was associated with higher plasma
      homocysteine levels. Furthermore, a high plasma homocysteine level was positively
      associated with behavioral disturbance among study participants with major
      depression. CONCLUSION: More behavioral disturbance associated with major
      depression occurred as the dementia progressed. Patients with a higher level of
      plasma homocysteine presented with a higher behavioral disturbance
      symptomatology. This finding may account for the relationship between elevated
      homocysteine levels and depression only in patients with moderate AD.

PMID- 20808088
TI  - Depression among older adults in the United States and England.
AB  - CONTEXT: Depression negatively affects health and well being among older adults,
      but there have been no nationally representative comparisons of depression
      prevalence among older adults in England and the United States. OBJECTIVE: The
      authors sought to compare depressive symptoms among older adults in these
      countries and identify sociodemographic and clinical correlates of depression in
      these countries. DESIGN AND SETTING: The authors assessed depressive symptoms in
      non-Hispanic whites aged 65 years and older in 2002 in two nationally
      representative, population-based studies: the U.S. Health and Retirement Study
      and English Longitudinal Study of Ageing. PARTICIPANTS: A total of 8,295 Health
      and Retirement Study respondents and 5,208 English Longitudinal Study of Ageing
      respondents. MAIN OUTCOME MEASURES: The authors measured depressive symptoms
      using the eight-item Center for Epidemiologic Studies Depression Scale. The
      authors determined whether depressive symptom differences between the United
      States and England were associated with sociodemographic characteristics, chronic
      health conditions, and health behaviors. RESULTS: Significant depressive symptoms
      (Center for Epidemiologic Studies Depression Scale score >=4) were more prevalent
      in English than U.S. adults (17.6% versus 14.6%, adjusted Wald test F([1, 1593])
      = 11.4, p < 0.001). Adjusted rates of depressive symptoms in England were 19%
      higher compared with the United States (odds ratio: 1.19, 95% confidence
      interval: 1.01-1.40). U.S. adults had higher levels of education, and net worth,
      but lower levels of activities of daily living/instrumental activities of daily
      living impairments, tobacco use, and cognitive impairment, which may have
      contributed to relatively lower levels of depressive symptoms in the United
      States. CONCLUSIONS: Older adults in the United States had lower rates of
      depressive symptoms than their English counterparts despite having more chronic
      health conditions. Future cross-national studies should identify how depression
      treatment influences outcomes in these populations.

PMID- 20808089
TI  - Prevalence of neuropsychiatric symptoms in chinese older persons with mild
      cognitive impairment-a population-based study.
AB  - OBJECTIVES: To estimate the point prevalence and correlates of neuropsychiatric
      (NP) symptoms among older adults with mild cognitive impairment (MCI) and normal
      cognition (NC) in a Chinese community. DESIGN: Cross-sectional study derived from
      a population-based prevalence study of MCI and dementia. SETTING AND
      PARTICIPANTS: This survey was conducted in Hong Kong from 2005 to 2006. Seven
      hundred eighty-eight community-dwelling older adults (450 NC and 338 MCI) were
      recruited. Cognitive and NP data were obtained. RESULTS: The point prevalence of
      at least one NP symptom in NC and MCI were 29% and 36.7%, respectively (logistic
      regression controlled for age and education, odds ratio = 1.38, 95% confidence
      interval [CI]: 1.01-1.89, Wald chi = 4.10, df = 1, p = 0.04). Agitation (1.8%
      versus 5.1%), apathy (7.6% versus 15.2%), and irritability (4.2% versus 8%) were
      more prevalent in subjects with MCI (p <0.05). Logistic regression analyses
      showed that apathy score was a significant factor associated with the status of
      NC or MCI (logistic regression, apathy, p = 0.031, Exp(B) = 1.23, 95% CI: 1.02
      1.47; Hosmer and Lemeshow test, chi = 8.6, df = 8, p = 0.38, R = 0.23).
      CONCLUSIONS: The authors reported the findings of one of the first population
      based studies estimating the point prevalence of NP symptoms in Asian older
      adults with MCI. Taking into account of its prevalence and magnitude of effects,
      apathy is a clinically significant symptom in MCI. Its predictive value for
      conversion to dementia warrants further evaluation.

PMID- 20808090
TI  - Agoraphobic cognitions in old and young patients with panic disorder.
AB  - OBJECTIVES: To compare the agoraphobic cognitions of younger and older patients
      suffering from panic disorder with agoraphobia by means of existing
      questionnaires. METHOD: Agoraphobic cognitions were assessed using the
      Agoraphobic Cognitions Questionnaire (ACQ) in 205 patients confirmed with
      confirmed panic disorder with agoraphobia (Diagnostic and Statistical Manual,
      Fourth Edition, Text Revision) and analyzed at the item level applying a
      Bonferroni correction. RESULTS: The 48 patients who were older than 60 years had
      a significantly lower mean (SD) ACQ total score than their younger counterparts
      (1.6 [0.5] versus 2.1 [0.6]; t = 5.7, df = 203, p < 0.001), with their scores on
      the items fear of going crazy, acting foolishly, losing control, passing out, and
      brain tumors (p < 0.004) being significantly lower. CONCLUSION: The differential
      effect at the ACQ item level suggests that some cognitions seem less relevant for
      agoraphobic panic disorder in later life. Future research should explore whether
      and which agerelated cognitions are missed in the current questionnaires.

PMID- 20808091
TI  - Comorbidity in aging and dementia: scales differ, and the difference matters.
AB  - BACKGROUND: Accurate assessment of the effect of dementia on healthcare
      utilization and costs requires separation of the effects of comorbid conditions,
      often poorly accounted for in existing claims-based studies. OBJECTIVE: To
      determine whether two different types of comorbidity and risk adjustment scales,
      the Chronic Disease Score (CDS) and the Cumulative Illness Rating Scale for
      Geriatrics (CIRS-G), perform similarly in older persons with and without
      dementia. METHODS: All subjects in the community-outreach diagnostic program of
      the University of Washington Alzheimer's Disease Research Center Satellite were
      included (N = 619). Subjects' mean age was 75 +/- 9 years; 40% were cognitively
      normal, 17% were cognitively impaired but not demented, and 43% were demented.
      CDS and CIRS-G scores (neuropsychiatric disorders excluded to reduce colinearity
      with group) were examined across strata of age, education, and cognitive
      classification by using analysis of variance, analysis of covariance, and linear
      regression. RESULTS: CIRS-G scores were sensitive to factors known to be
      associated with chronic disease burden, including age (F = 21.3 [df = 2, 616], p
      <0.001), education (F = 6.6 [df = 3, 614], p <0.001), and cognitive status (F =
      40.5 [df = 2, 616], p <0.001), whereas the CDS was not. In the subset of persons
      with CDS scores of 0 (40% of the total sample), CIRS-G scores ranged from very
      low to high burden of disease and remained significantly different across age,
      education, and cognitive status groups. In regression analyses predicting CIRS-G
      score, CDS score and cognitive status interacted (beta = -0.10, t = 1.9 [df = 1,
      609], p = 0.06). After controlling for age, the amount of variance shared by the
      CIRS-G-13 and CDS differed by cognitive group (>32% for normal and mildly
      impaired groups combined, 17% for dementia). CONCLUSION: Different methods of
      measuring and adjusting for comorbidity are not equivalent, and dementia
      amplifies the discrepancies. The CDS, if used to control for comorbidity in
      comparative studies of healthcare utilization and costs for persons with and
      without dementia, will underestimate burden of comorbid disease and artificially
      inflate the costs attributed to dementia.

PMID- 20808092
TI  - Home-delivered problem adaptation therapy (PATH) for depressed, cognitively
      impaired, disabled elders: A preliminary study.
AB  - OBJECTIVES: This preliminary study examines the efficacy of 12-week home
      delivered problem adaptation therapy (PATH) versus home-delivered supportive
      therapy (ST) in reducing depression and disability in 30 depressed, cognitively
      impaired, disabled older adults. DESIGN: A 12-week randomized clinical trial.
      Research assistants were unaware of the participants' randomization status.
      Assessments were conducted at baseline, 6 weeks, and 12 weeks. SETTING: Weill
      Cornell Advanced Center for Interventions and Services Research. PARTICIPANTS:
      Thirty elders with major depression, cognitive impairment, and disability were
      recruited through advertisement and the Home-Delivered Meals Program of the
      Westchester County Department of Senior Programs and Services. INTERVENTION: PATH
      is a home-delivered intervention designed to reduce depression and disability in
      depressed, cognitively impaired, disabled elders. PATH is based on problem
      solving therapy and integrates environmental adaptation and caregiver
      participation. PATH is consistent with Lawton's ecologic model of adaptive
      functioning in aging. MEASUREMENTS: Depression and disability were measured with
      Hamilton Depression Rating Scale-24 items and Sheehan Disability Scale,
      respectively. Client Satisfaction Questionnaire was used to assess patient
      satisfaction with treatment. RESULTS: Mixed-effects model analyses revealed that
      PATH was more efficacious than ST in reducing depression and disability at 12
      weeks. Participants in both treatment groups were satisfied with treatment.
      CONCLUSIONS: This preliminary study suggests that PATH is well accepted and
      efficacious in depressed elders with major depression, cognitive impairment, and
      disability. Because this population may not adequately respond to antidepressant
      medication treatment, PATH may provide relief to many patients who would
      otherwise remain depressed and continue to suffer.

PMID- 20808093
TI  - Successful aging in older adults with schizophrenia: prevalence and associated
      factors.
AB  - OBJECTIVE: This study contrasts the prevalence of successful aging in older
      adults with schizophrenia with their age peers in the community and examines
      variables associated with successful aging in the schizophrenia group. METHODS:
      The schizophrenia group consisted of 198 community-dwelling persons aged 55 years
      and older who developed schizophrenia before the age of 45 years. A community
      comparison group (N = 113) was recruited using randomly selected block groups.
      The three objective criteria proposed by Rowe and Kahn were operationalized using
      a six-item summed score. The association of 16 predictor variables with the
      successful aging score in the schizophrenia group was examined. RESULTS: The
      community group had significantly higher successful aging scores than the
      schizophrenia group (4.3 versus 3.0; t = 8.36, df = 309, p <0.001). Nineteen
      percent of the community group met all six criteria on the successful aging score
      versus 2% of the schizophrenia group. In regression analysis, only two variables
      fewer negative symptoms and a higher quality of life index-were associated with
      the successful aging score within the schizophrenia group. CONCLUSION: Older
      adults with schizophrenia rarely achieve successful aging and do so much less
      commonly than their age peers. Only two significant variables were associated
      with successful aging neither of which are easily remediable. The elements that
      comprise the components of successful aging, especially physical health, may be
      better targets for intervention.

PMID- 20808094
TI  - Screening and case-finding tools for the detection of dementia. Part II: evidence
      based meta-analysis of single-domain tests.
AB  - AIM: To evaluate the diagnostic validity of single-domain cognitive tests for
      detecting dementia. These methods were defined as those that focus mainly on one
      domain of cognitive function such as orientation, memory, or executive function.
      METHODS: A meta-analysis of robust studies was conducted. There were 15
      categories of single-domain methods assessed in 45 analyses, including 27
      performed head-to-head against the Mini-Mental State Examination (MMSE). Thirteen
      studies took place in community settings, 9 in primary care, and 23 in specialist
      settings. RESULTS: In community settings, single-domain cognitive tests helped
      detect 64.2% of all dementias. In this setting, specificity (Sp) was 84.9%,
      positive predictive value (PPV) was 57.1%, and negative predictive value (NPV)
      was 88.3%. This was significantly less accurate than the MMSE itself. The optimal
      individual method was the memory impairment screen (MIS). In primary care, the
      sensitivity (Se) and specificity of single-domain tests were 69.5% and 82.5%,
      respectively. The PPV and NPV were 36.5% and 95.8%. Considered together, these
      methods were less specific but equally sensitive as the MMSE when applied in
      primary care. Here, the most successful methods were the selective reminding test
      (SRT) and clock drawing test, the latter having data from independent samples. In
      specialist settings, single-domain methods had a Se of 76.6%, a Sp of 81.9%, a
      PPV 80.8%, and a NPV 74.9%. This represented almost equivalent accuracy to the
      MMSE. The optimal method for specialist settings (based on accuracy alone) was
      the memory alteration test. CONCLUSION: Brief single-domain methods offer
      diagnostic performance for detection of dementia that is surprisingly close to
      that offered by cognitive batteries such as the MMSE. As a method of screening or
      as part of a diagnostic algorithm, brief single-domain tests may be an efficient
      first step in identifying cognitive impairment.

PMID- 20808095
TI  - Depression, physical function, and risk of mortality: National Diet and Nutrition
      Survey in adults older than 65 years.
AB  - OBJECTIVE: the authors used an objective assessment of physical function and a
      range of sociodemographic, dietary, and health behaviors to explore the possible
      factors that could explain the association between depression and mortality in
      community-dwelling elderly participants aged 65 years and older. DESIGN:
      prospective follow-up of the National Diet and Nutrition Survey in older adults.
      SETTING: community sample. PARTICIPANTS: a total of 1,007 participants (522 men,
      485 women; mean age: 76.4 +/- 7.3 years). MEASUREMENTS: : Depression was assessed
      from the 15 item Geriatric Depression Scale (GDS) and physical function using
      hand grip strength. Participants were followed up for death over an average of
      9.2 years. RESULTS: : At baseline, 20.9% of participants demonstrated depression
      (GDS-15 score >= 5). Depressed participants were at a higher relative risk of all
      cause mortality during follow-up (age- and sex-adjusted hazard ratio = 1.24, 95%
      confidence interval: 1.04-1.49). Other risk factors for depression also related
      to mortality included smoking, physical inactivity, and low grip strength. These
      factors collectively explained an estimated 54% of the association between
      depression and mortality. Low-grade inflammation and low plasma vitamin C were
      also independently associated with depression and mortality but did not explain
      any of the association between depression and mortality. CONCLUSION: late-life
      depression is associated with a higher risk of mortality. Physical inactivity and
      physical dysfunction might partly mediate this association, although further
      longitudinal studies are required to fully elucidate these mechanisms.

PMID- 20808096
TI  - Morphometric analysis of neuronal and glial cell pathology in the caudate nucleus
      in late-life depression.
AB  - OBJECTIVE: To assess glial and neuronal density and neuronal volume in two areas
      of the caudate nucleus in late-life major depression. DESIGN: A postmortem study
      using the disector and nucleator methods to estimate neuronal density and volume
      and glial density of cells from human brain tissue from the anterior portion
      (dorsolateral and ventromedial aspects) of the caudate nucleus. SETTING: Brain
      tissues were obtained from the Newcastle Brain Tissue Resource at Newcastle
      University, UK. PARTICIPANTS: The study group consisted of 13 subjects with late
      life major depression and nine comparison subjects of similar age. RESULTS:
      Evidence of moderate reductions in neuronal density was found in the depressed
      group in both the dorsolateral and ventromedial areas of the caudate nucleus.
      There were no significant changes in glial density or neuronal volume in either
      area nor was there any evidence of differences in depression in early and late
      onset subgroups. CONCLUSIONS: Neuroimaging abnormalities in frontal and
      subcortical areas including ischemic hyperintensities and a reduction in volume
      and metabolism in the caudate nucleus have been reported in late-life depression,
      and previous morphometric studies have reported neuronal changes in prefrontal
      cortical areas. The findings in this study extend these morphometric
      investigations in late-life depression to the caudate nucleus, suggesting that
      neuronal abnormalities are present in this subcortical nucleus as well as in
      these related prefrontal areas.

PMID- 20808097
TI  - Self-efficacy buffers the relationship between dementia caregiving stress and
      circulating concentrations of the proinflammatory cytokine interleukin-6.
AB  - OBJECTIVE: the proinflammatory cytokine interleukin (IL)-6 has been linked with
      health morbidity, particularly risk for cardiovascular disease (CVD). The purpose
      of this study was to investigate the potential protective role of coping self
      efficacy on the relationship between caregiving stress and circulating
      concentrations of IL-6. METHODS: a total of 62 elderly caregivers of patients
      with Alzheimer's disease (mean age: 74 years) were assessed for plasma
      concentrations of IL-6, caregiving-related overload, and coping self-efficacy.
      Multiple regression was used to examine the main effects of stress and self
      efficacy, as well as the interaction between stress and self-efficacy, in
      predicting plasma IL-6 after controlling for age, gender, resting blood pressure,
      and obesity. RESULTS: there was a significant interaction between stress and self
      efficacy in predicting IL-6. Post-hoc examination indicated that when self
      efficacy was low, stress was significantly related to IL-6 (beta = 0.43).
      However, when self-efficacy was high, stress was not significantly related to IL
      6 (beta = -0.10). CONCLUSION: caregiving stress in combination with low coping
      self-efficacy is significantly related to IL-6, a known risk marker for health
      morbidity, particularly CVD. However, stress was not associated with IL-6 with
      high self-efficacy. Although limited and preliminary, these results point to a
      potential protective effect of self-efficacy on caregiver health that can be
      tested in longitudinal studies.

PMID- 20808098
TI  - Social inequalities in the occurrence of suicidal ideation among older primary
      care patients.
AB  - OBJECTIVES: To examine whether there is an association between area socioeconomic
      status and the experience of suicidal ideation among older adults. DESIGN:
      Secondary analyses of data from a prospective study of naturalistic outcomes of
      depressive symptoms. SETTING: Monroe County, NY. PARTICIPANTS: A cohort of older
      adults (>=65 years, N = 515) attending primary care settings. MEASUREMENTS: Area
      socioeconomic status was based on the median household incomes of the census
      tracts (CTs) in which participants lived. At 6- and 12-month follow-up, the
      longitudinal interval follow-up evaluation was used to assess weekly depressive
      symptom status over the previous 6 months, which was used to construct a measure
      of any suicidal ideation during the study. RESULTS: Residents of CTs with median
      household incomes of less than $30,000/yr were more likely to experience suicidal
      ideation than residents of higher income CTs (unadjusted odds ratio [OR], 4.60;
      95% confidence interval [CI], 1.64-12.86). Adjustment for demographic and
      baseline clinical factors did not eliminate the association (OR, 5.44; 95% CI,
      1.71-17.24). Subsequent models that adjusted for medical, functional, and
      psychosocial variables did not explain this association either. CONCLUSIONS:
      There is a robust association between lower CT income and the occurrence of
      suicidal ideation in a primary care cohort of older adults over 1 year. These
      findings indicate the need for more research into how social worlds come to
      influence the emotional well being of older adults and whether social factors
      such as CT income can be used to identify individuals at increased risk for
      suicidal behavior.

PMID- 20808099
TI  - A new home-based mental health program for older adults: description of the first
      100 cases.
AB  - BACKGROUND: The Geriatric Psychiatry Outreach (GO) Program began in 2005 and
      provides in-home psychiatric evaluation and treatment for older adults who have
      difficulty getting to an office-based setting. METHOD: An initial assessment was
      conducted on the first 100 patients seen by the program and follow-up treatment
      was provided as clinically indicated. RESULTS: The mean age of patients seen was
      79.7 (SD: 8.2), 74% were women, and the most common psychiatric diagnoses were
      depression (50%) and dementia (45%), with a mean of 1.4 (SD: 0.6) psychiatric
      diagnoses per patient. The patients had a mean of 4.8 (SD: 2.9) medical diagnoses
      and were on a mean of 6.8 (SD: 4.0) prescription and 2.2 (SD: 1.2)
      nonprescription medications. Patients received a mean of 4.2 (SD: 4.2) in-person
      visits and a mean of 30.2 (SD: 36.5) additional contacts related to their care,
      such as phone calls, e-mails, and faxes. CONCLUSIONS: Providing psychiatric
      services at home for older adults with mental illness is a much needed but rarely
      available service. Such patients typically have a complex combination of medical
      and psychiatric diagnoses and benefit from contacts in addition to the face-to
      face visits.

PMID- 20808100
TI  - Anosognosia in mild cognitive impairment and mild Alzheimer's disease: frequency
      and neuropsychological correlates.
AB  - OBJECTIVES: To evaluate severity of anosognosia and to identify its
      neuropsychological correlates in preclinical and clinical Alzheimer's Disease
      (AD). METHODS: The Clinical Insight Rating Scale, the Anosognosia Questionnaire
      for Dementia (AQ-D), and the Mental Deterioration Battery were used to assess
      anosognosia and cognitive performances in mild AD (N = 38), amnesic mild
      cognitive impairment (a-MCI; N = 35), and multiple domain MCI (md-MCI; N = 38).
      RESULTS: Patients with mild AD were more anosognosic than both MCI groups, which,
      however, did not differ from one other. A categorical diagnosis of anosognosia
      was made in 42% of patients with mild AD, 3% of md-MCI, but in no subjects with a
      MCI. Reduced verbal episodic memory raw score was associated with decreased
      awareness of cognitive difficulties (AQ-D total and intellectual functioning
      scores) only in MCI. In mild AD, anosognosia was linked only to increased age and
      reduced basic activities of daily living performances. CONCLUSIONS: The diagnosis
      of anosognosia is frequent in patients with mild AD but not in those with MCI. In
      the latter case, the authors cannot speak of true anosognosia but only of
      decreased awareness of illness. Furthermore, reduced awareness of cognitive
      difficulties is linked with verbal memory performances in patients with MCI but
      not in those with AD, suggesting for the latter the involvement of factors other
      than neuropsychological. Thus, neuropsychiatric dimensions commonly present in
      patients with AD should be investigated along with anosognosia.

PMID- 20808101
TI  - A memory and organizational aid improves Alzheimer disease research consent
      capacity: results of a randomized, controlled trial.
AB  - OBJECTIVES: Early and progressive cognitive impairments of patients with
      Alzheimer disease (AD) hinder their capacity to provide informed consent.
      Unfortunately, the limited research on techniques to improve capacity has shown
      mixed results. Therefore, the authors tested whether a memory and organizational
      aid improves the performance of patients with AD on measures of capacity and
      competency to give informed consent. DESIGN, SETTING, AND PARTICIPANTS: Patients
      with AD randomly assigned to standard consent or standard plus a memory and
      organizational aid. INTERVENTION: Memory and organizational aid summarized the
      content of information mandated under the informed consent disclosure
      requirements of the Common Rule at a sixth grade reading level. MEASUREMENTS:
      Three psychiatrists without access to patient data independently reviewed
      MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) interview
      transcripts to judge whether the patient was capable of providing informed
      consent. The agreement of at least two of the three experts defined a participant
      as capable of providing informed consent. Secondary outcomes are MacCAT-CR
      measures of understanding, appreciation and reasoning, and comparison with
      cognitively normal older adult norms. RESULTS: AD intervention and control groups
      were similar in terms of age, education, and cognitive status. The intervention
      group was more likely to be judged competent than control group and had higher
      scores on MacCAT-CR measure of understanding. The intervention had no effect on
      the measures of appreciation or reasoning. CONCLUSIONS: A consent process that
      addresses the deficits in memory and attention of a patient with AD can improve
      capacity to give informed consent for early phase AD research. The results also
      validate the MacCAT-CR as an instrument to measure capacity, especially the
      understanding subscale. TRIAL REGISTRY: ClinicalTrials.Gov#NCT00105612,
      http://clinicaltrials.gov/show/NCT00105612.

PMID- 20808103
TI  - Treatment of subsyndromal depressive symptoms in middle-age and older patients
      with schizophrenia: effect of age on response.
AB  - OBJECTIVE: The authors hypothesized that age would moderate the response of
      patients with schizophrenia and subsyndromal depression (SSD) treated citalopram
      with depressive symptoms and other outcomes. Also, older patients would exhibit
      more side effects with citalopram. METHODS: Participants of 40 years or older had
      schizophrenia or schizoaffective disorder with SSD. Patients randomly received
      flexible dosing of citalopram or placebo augmentation of their antipsychotic
      medication. Linear regression determined whether age had any moderating effect on
      depressive symptoms, global psychopathology, negative symptoms, mental
      functioning, and quality of life. Age-related side effects were examined.
      RESULTS: There were no significant drug group by age interaction in depressive or
      psychotic symptoms, mental Short Form-12, or quality of life scores. Similarly,
      there were few age-related side effect differences. CONCLUSION: Symptoms in
      younger and older patients with schizophrenia and SSD treated with citalopram
      seem to respond similarly. Adverse events do not seem to differ with age.

PMID- 20808102
TI  - Screening depression aging services clients.
AB  - OBJECTIVES: To establish the psychometric characteristics of the Patient Heath
      Questionnaire (PHQ) (PHQ-2, -9, and their sequential administration) in older
      adults who use community-based, social service care management. DESIGN:
      Comparison of screening tools with criterion standard diagnostic interview.
      SETTING: A community-based aging services agency. PARTICIPANTS: Three hundred
      seventy-eight adults aged 60 years or older undergoing in-home aging services
      care management assessments. MEASUREMENTS: Subjects were administered the PHQ-9
      and Structured Clinical Interview for DSM-IV-TR- fourth edition. The authors
      examined the sensitivity, specificity, positive and negative predictive values,
      positive and negative likelihood ratios, and receiver operating characteristic
      (ROC) curve for the PHQ-2 and PHQ-9 separately, and for a two-stage screening
      process that used each in sequence (the PHQ-2/9). RESULTS: Using a cut score of
      3, the sensitivity of the PHQ-2 was 0.80 and the specificity was 0.78. The area
      under the ROC curve (AUC) for the PHQ-2 was 0.87. Using a cut score of 10, the
      sensitivity and specificity of the PHQ-9 were 0.82 and 0.87. The AUC was 0.91.
      The sensitivity and specificity of the two-stage PHQ-2/9 were 0.81 and 0.89,
      respectively, and the AUC was 0.91. CONCLUSIONS: The greater specificity of the
      PHQ-9 is an advantage over the PHQ-2 in aging service settings in which false
      positive tests have potentially high cost. The PHQ-2/9 performed equally well as
      the PHQ-9, but would be more efficient for the agency to administer. Combined
      with an appropriate referral system to healthcare providers, use of the PHQ-2/9
      sequence by aging services personnel can efficiently assist in reducing the
      burden of late-life depression.

PMID- 20808104
TI  - Cerebrovascular risk factors and cerebral hyperintensities among middle-aged and
      older adults with major depression.
AB  - OBJECTIVES: To examine the association between cerebral hyperintensities and
      cerebrovascular risk factors (CVRF) among middle-aged and older adults with major
      depressive disorder (MDD). METHODS: Thirty patients (aged 55-77 years) with MDD
      and no history of stroke participated in a magnetic resonance imaging assessment
      to assess for the presence of cerebral hyperintensities and underwent a physical
      examination to assess stroke risk as indexed by the Framingham Stroke Risk
      Profile (FSRP). In addition, intima medial thickness (IMT) was measured in the
      left and right carotid arteries. RESULTS: Higher FSRP levels were associated with
      total greater cerebral hyperintensities (r = 0.64), as well as greater
      subependymal hyperintensities (r = 0.47), confluent periventricular changes (r =
      0.46), and tended to be associated with subcortical gray matter hyperintensities
      (r = 0.34). A quadratic relationship was observed between IMT and total cerebral
      hyperintensities (b = 4.84), and higher IMT levels were associated with greater
      subependymal hyperintensities (r = 0.40). CONCLUSIONS: Higher levels of CVRF are
      associated with graded increases in cerebral hyperintensities among middle-aged
      and older adults with MDD.

PMID- 20808106
TI  - Plasma amyloid beta-42 independently predicts both late-onset depression and
      Alzheimer disease.
AB  - OBJECTIVES: Depression in the elderly might represent a prodromal phase of
      Alzheimer disease (AD). High levels of plasma amyloid beta-42 (Abeta42) were
      found in prestages of AD and also in depressed patients in cross-sectional
      studies. This study examined the association of emerging late-onset depression
      (LOD) and AD with plasma Abeta42 in a sample of never depressed and not demented
      persons at baseline. DESIGN: Prospective 5-year longitudinal study. PARTICIPANTS:
      A community dwelling of older adults (N = 331) from the Vienna Transdanube Aging
      study. MEASUREMENTS: Laboratory measurements, cognitive functioning, and
      depressive symptoms were assessed at baseline, 2.5, and 5 years follow-ups.
      RESULTS: After exclusion of converters to AD, regression analysis revealed that
      higher plasma Abeta42 at baseline was a positive predictor for conversion to
      first episode of LOD. Independent of whether persons with mild cognitive
      impairment (MCI) at 2.5 years were included or excluded into regressions, higher
      plasma Abeta42 at baseline was a significant predictor for the development of
      probable or possible AD at 5 years. Higher conversion to AD was also associated
      with male gender but not with either higher scores on the Geriatric Depression
      Scale (GDS), with stroke or cerebral infarction nor apolipoprotein E epsilon4
      allele. No association was found for an interaction between plasma Abeta42 levels
      and GDS. CONCLUSIONS: Higher plasma Abeta42 at baseline predicted the development
      of first episode of LOD and conversion to probable or possible AD. Emerging
      depression as measured by scores on GDS at the 2.5-year follow-up, either alone
      or as an interaction factor with plasma Abeta42, failed to predict the conversion
      to AD at 5 years.

PMID- 20808105
TI  - Correlates of perceived need for and use of mental health services by older
      adults in the collaborative psychiatric epidemiology surveys.
AB  - OBJECTIVES: Older adults are especially unlikely to seek mental health services,
      but little is known about whether their perceptions of need for help contribute
      to this problem. The objectives of this study were to compare perceived need
      across the lifespan and to examine sociodemographic and mental health correlates
      of whether older adults sought professional help, perceived the need for help
      without seeking it, and sought help from specialty mental health professionals.
      METHODS: The authors examined help-seeking and perceived need with the
      Collaborative Psychiatric Epidemiology Surveys, focusing on 3,017 adults aged 55
      years and older. Logistic regressions predicted help-seeking and perceived need
      from sociodemographic factors, past-year psychiatric disorders, and past-year
      suicidal behaviors. Individuals who perceived the need for help without receiving
      it also reported barriers to help-seeking. RESULTS: Levels of perceived need were
      highest among 25-44 year olds and lowest among adults aged 65 years and older.
      Among older adults with psychiatric disorders, 47.1% did not perceive a need for
      professional help. Diagnoses and suicidal behaviors were strong predictors of
      whether individuals perceived need, whereas among those who perceived the need
      for help, only older age was positively associated with help-seeking. Few factors
      clearly distinguished those who did and did not seek help from specialty mental
      health professionals with the exception of having three or more psychiatric
      diagnoses. Finally, the most common barrier to help-seeking was a desire to
      handle problems on one's own. CONCLUSIONS: A lack of perceived need for mental
      health services and self-sufficiency beliefs are significant barriers to older
      adults' use of mental health services.

PMID- 20808107
TI  - Change in hippocampal volume on magnetic resonance imaging and cognitive decline
      among older depressed and nondepressed subjects in the neurocognitive outcomes of
      depression in the elderly study.
AB  - INTRODUCTION: previous studies have linked hippocampal volume change and
      cognitive decline in older adults with dementia. The authors examined hippocampal
      volume change and cognitive change in older nondemented adults with and without
      major depression. METHODS: the sample consisted of 90 depressed individuals and
      72 healthy, nondepressed individuals aged 60 years and older who completed at
      least 2 years of follow-up data. All patients underwent periodic clinical
      evaluation by a geriatric psychiatrist as well as baseline and 2-year magnetic
      resonance imaging. RESULTS: over 2 years, the depressed group showed a greater
      reduction in left hippocampal volume (normalized for total cerebral volume)
      compared with the nondepressed group (mean difference = 0.013 +/- 0.0059, t =
      2.18, df = 160, p <0.0305). The difference remained significant after controlling
      for age, sex, and baseline normalized left hippocampal volume. The authors also
      found that hippocampal change from baseline to 2 years was associated with
      subsequent change in Mini-Mental State Examination score from 2 years to 21/2
      years (left t = 2.81, df = 66, p = 0.0066; right t = 2.40, df = 66, p = 0.0193)
      among the depressed group. CONCLUSIONS: these findings add to the literature
      linking hippocampal volume loss and late-life depression. Depressed patients with
      hippocampal volume loss are at greater risk of cognitive decline.

PMID- 20808109
TI  - Outcomes of a two-tiered multifaceted elderly suicide prevention program in a
      Hong Kong Chinese community.
AB  - OBJECTIVES: 1) To compare the 2-year completed suicide and reattempt rates in a
      preintervention group of Hong Kong Chinese suicide attempters (aged 65 years and
      older) who received standard care and a postintervention group enrolled in a
      regional elderly suicide prevention program (ESPP) that adopts a two-tiered
      multifaceted care management model and 2) to examine the trend of suicide rates
      in older adults aged 65 years and older in the pre- and postintervention periods.
      DESIGN: The first part is an observational cohort study with baseline, follow-up,
      and outcome data being identified from a clinical electronic registry. The second
      part examines changes in suicide rates from official mortality statistics.
      SETTING: A government-funded suicide intervention program serving catchment
      population (852,796 people aged 65 years and older) in Hong Kong, China.
      PARTICIPANTS: Suicide attempters (aged 65 years and older) presenting to old-age
      psychiatric service in the pre- and postintervention phases. MEASUREMENTS: 1) Two
      year rates of completed suicide and suicide reattempt and 2) changes in
      population suicide rates in the pre- and postintervention periods. RESULTS: The 2
      year completed suicide rate was 7.58% in the preintervention group (N = 66) and
      1.99$% in the ESPP group (N = 351) Chi = 6.192; p value: 0.028; df = 1).
      Reattempt rates were not different. At a population level, suicide rate dropped
      significantly only in women aged 85 years and older, relative to the
      preintervention period. CONCLUSIONS: The ESPP was associated with a reduced rate
      of completed suicide in old-age suicide attempters and might have contributed to
      a fall of suicide rate in women aged 85 years and older.

PMID- 20808108
TI  - Caregiver burden in Alzheimer disease: cross-sectional and longitudinal patient
      correlates.
AB  - OBJECTIVES: Alzheimer disease (AD) imposes a severe burden on patients and their
      caregivers. Although there is substantial evidence of the adverse impact of
      burden, considerably less is known about its specific correlates and potential
      causes. DESIGN: The authors use data from the Clinical Antipsychotic Trials of
      Intervention Effectiveness (CATIE)-AD study to examine the relationship of burden
      and depression among AD caregivers to patient and caregiver sociodemographic
      characteristics, patients' cognitive status, psychiatric and behavioral symptoms,
      functional abilities, quality of life, and intensity of care provided by
      caregivers. SETTING: CATIE-AD included outpatients in usual care settings and
      assessed treatment outcomes during 9 months. PARTICIPANTS: Data were examined
      from 421 ambulatory outpatients with a diagnosis of dementia of the Alzheimer
      type or probable AD with agitation or psychosis. MEASURES: The Burden Interview,
      the Beck Depression Inventory, and the Caregiver Distress Scale were used to
      evaluate caregiver burden. RESULTS: More severe psychiatric and behavioral
      problems and decreased patient quality of life, as well as lower functional
      capability were significantly associated with higher levels of burden and
      depression among caregivers at baseline. Six-month changes showed that decreased
      symptoms and improved quality of life were associated with decreased burden and
      accounted for most of the explained variance in change in burden measures.
      CONCLUSION: Severity of psychiatric symptoms, behavioral disturbances, and
      patients' quality of life are the main correlates of caregivers' experience
      burden. Psychosocial and pharmacologic interventions targeting these two aspects
      of the disorder are likely to not only alleviate patient suffering but also
      promote caregiver well-being.

PMID- 20808110
TI  - Prediabetes assessment and follow-up in older veterans with schizophrenia.
AB  - OBJECTIVES: Assess glycemic monitoring and follow-up. DESIGN: Retrospective study
      using administrative data (October 2001-September 2005). SETTING: Veterans Health
      Administration. PARTICIPANTS: A nationwide sample of 39,226 outpatients aged 50
      years or older with schizophrenia. Patients had no diagnosis or medications for
      diabetes at baseline. MEASUREMENTS: Hemoglobin A1c tests; blood glucose tests
      with same-day low-density lipoprotein to approximate fasting glucose. Glycemic
      tests were combined to indicate a) prediabetic dysglycemia (100-125 mg/dL proxy
      fasting glucose or 5.8%-6.4% hemoglobin A1c) and b) diabetic dysglycemia (>=126
      proxy fasting glucose or >=6.5% A1c). RESULTS: Approximately one-third of
      patients (32%; 12,587) had proxy fasting blood glucose or A1c tests in 2002;
      multiple tests were rare. The proportion tested increased to 40% by 2005. Test
      results suggested prediabetic dysglycemia for 5,345 tested patients (42% of those
      tested) and diabetic dysglycemia for 1,287 tested patients (10%) at baseline. In
      multivariate regression models, glycemic testing was associated with
      dyslipidemia, hypertension, and younger age. Dysglycemia was associated with
      hypertension, dyslipidemia, and older age. Follow-up treatment/diagnosis of
      diabetes occurred for 8% of patients (11% of those tested) and was associated
      with baseline dysglycemia, hypertension, and younger age. Mortality (15% during
      the 4-year study) was higher among untested and untreated patients. CONCLUSIONS:
      Dysglycemia was prevalent among older patients with schizophrenia, although
      monitoring and follow-up were uncommon. Follow-up treatment correlated with
      survival. Despite evident utility of testing, few at-risk patients with
      schizophrenia were adequately monitored, diagnosed, or treated for dysglycemia.

PMID- 20808111
TI  - Cognitive slowing associated with elevated serum anticholinergic activity in
      older individuals is decreased by caffeine use.
AB  - OBJECTIVES: This study examined whether some of the age-associated decrements in
      basic cognitive resources (information-processing speed and working memory)
      result from anticholinergic medication use (as measured by serum anticholinergic
      activity [SAA]) and whether such decrements are lessened by caffeine. DESIGN:
      Cross-sectional observational study. SETTING: University medical center.
      PARTICIPANTS: One hundred fifty-two normal-elderly community volunteers.
      MEASUREMENTS: Two tests each of information-processing speed and of working
      memory were administered, and blood samples were drawn before and after cognitive
      testing to determine serum levels of anticholinergic activity and of paraxanthine
      a caffeine metabolite. RESULTS: Elevated SAA was associated with a significant
      but modest slowing in information-processing time but only in those individuals
      who had low levels of serum paraxanthine. SAA did not correlate with performance
      on tests of working memory. CONCLUSIONS: These results suggest that
      anticholinergic medications are a relatively minor contributor to the decrements
      in basic processing resources commonly found in studies of normal aging.

PMID- 20808112
TI  - Sleep-disordered breathing in Vietnam veterans with posttraumatic stress
      disorder.
AB  - OBJECTIVE: : To study the prevalence of sleep-disordered breathing (SDB) in
      Vietnam- era veterans. METHODS: : This was an observational study of Vietnam-era
      veterans using unattended, overnight polysomnography, cognitive testing, and
      genetic measures. RESULTS: : A sample of 105 Vietnam-era veterans with
      posttraumatic stress disorder: 69% had an Apnea Hypopnea Index >10. Their mean
      body mass index was 31, "obese" by Centers for Disease Control and Prevention
      criteria, and body mass index was significantly associated with Apnea Hypopnea
      Index (Spearman r = 0.41, N = 97, p < 0.0001). No significant effects of sleep
      disordered breathing or apolipoprotein status were found on an extensive battery
      of cognitive tests. CONCLUSION: : There is a relatively high prevalence of SDB in
      these patients which raises the question of to what degree excess cognitive loss
      in older PTSD patients may be due to a high prevalence of SDB.

PMID- 20808114
TI  - Enhancing memory in late-life depression: the effects of a combined
      psychoeducation and cognitive training program.
AB  - OBJECTIVE: To evaluate the efficacy of a multifactorial cognitive training (CT)
      program for older people with a lifetime history of depressive disorder. METHODS:
      This was a single-blinded waitlist control design. The study was conducted in the
      Healthy Brain Ageing Clinic, a specialist outpatient clinic at the Brain & Mind
      Research Institute, Sydney, Australia. Forty-one participants (mean age = 64.8
      years, sd = 8.5) with a lifetime history of major depression were included. They
      were stabilized on medication and had depressive symptoms in the normal to mild
      range. The intervention encompassed both psychoeducation and CT. Each component
      was 1-hour in duration and was delivered in a group format over a 10-week period.
      Psychoeducation was multifactorial, was delivered by health professionals and
      targeted cognitive strategies, as well depression, anxiety, sleep, vascular risk
      factors, diet and exercise. CT was computer-based and was conducted by Clinical
      Neuropsychologists. Baseline and follow-up neuropsychological assessments were
      conducted by Psychologists who were blinded to group allocation. The primary
      outcome was memory whilst secondary outcomes included other aspects of cognition
      and disability. RESULTS: CT was associated with significant improvements in
      visual and verbal memory corresponding to medium to large effect sizes.
      CONCLUSION: CT may be a viable secondary prevention technique for late-life
      depression, a group who are at risk of further cognitive decline and progression
      to dementia.

PMID- 20808113
TI  - Insomnia symptoms in older adults: associated factors and gender differences.
AB  - OBJECTIVES: the aim of this study was to examine the factors associated with
      insomnia in community-dwelling elderly as a function of the nature and number of
      insomnia symptoms (IS), e.g., difficulty with initiating sleep (DIS), difficulty
      with maintaining sleep (DMS), and early morning awakening (EMA). METHODS: is were
      assessed in a sample of 2,673 men and 3,213 women aged 65 years and older. The
      participants were administered standardized questionnaires regarding the
      frequency of IS and other sleep characteristics (snoring, nightmares, sleeping
      medication, and sleepiness) and various sociodemographic, behavioral and clinical
      variables, and measures of physical and mental health. RESULTS: more than 70% of
      men and women reported at least one IS, DMS being the most prevalent symptom in
      both men and women. Women reported more frequently two or three IS, whereas men
      reported more often only one IS. Multivariate regression analyses stratified by
      gender showed that men and women shared numerous factors associated with IS,
      sleeping medication, nightmares, sleepiness, chronic diseases, and depression
      being independently associated with two or three IS. For both sexes, age was
      associated with only one IS in all age categories. Loud snoring was strongly
      associated with increased DMS in men only. High body mass index increased the
      risk for DIS in men but tended to decrease it in women. In women, hormonal
      replacement therapy, Mediterranean diet, and caffeine and alcohol intake had a
      protective effect. CONCLUSION: our data suggest that women may have specific
      predisposition factors of multiple IS, which may involve both behavioral and
      hormonal factors. Identification and treatment of these risk factors may form the
      basis of an intervention program for reduction of IS in the elderly.

PMID- 20808115
TI  - Purpose in life is associated with a reduced risk of incident disability among
      community-dwelling older persons.
AB  - BACKGROUND: Purpose in life is thought to be associated with positive health
      outcomes in old age, but its association with disability is unknown. OBJECTIVE:
      Test the hypothesis that greater purpose in life is associated with a reduced
      risk of incident disability, including impairment in basic and instrumental
      activities of daily living and mobility disability, among community-based older
      persons free of dementia. DESIGN: Participants were from the Rush Memory and
      Aging Project, a large longitudinal clinical-pathologic study of aging. SETTING:
      Retirement communities, senior housing facilities, and homes across the greater
      Chicago metropolitan area. MEASUREMENTS: All participants underwent baseline
      assessment of purpose in life and detailed annual clinical evaluations to
      document incident disability. RESULTS: The mean score on the purpose in life
      measure at baseline was 3.6 (standard deviation = 0.5, range: 2-5). In a series
      of proportional hazards models adjusted for age, sex, and education, greater
      purpose in life was associated with a reduced risk of disability in basic
      activities of daily living (hazard ratio [HR] = 0.60, 95% confidence interval
      [C1] = 0.45-0.81), instrumental activities of daily living (HR = 0.56, 95% CI =
      0.40-0.78), and mobility disability (HR = 0.61, 95% CI = 0.44-0.84). These
      associations did not vary along demographic lines and persisted after the
      addition of terms to control for global cognition, depressive symptoms, social
      networks, neuroticism, income, physical frailty, vascular risk factors, and
      vascular diseases. CONCLUSIONS: Among community-based older persons without
      dementia, greater purpose in life is associated with maintenance of functional
      status, including a reduced risk of developing impairment in basic and
      instrumental activities of daily living and mobility disability.

PMID- 20808116
TI  - Trajectory of cognitive decline as a predictor of psychosis in early Alzheimer
      disease in the cardiovascular health study.
AB  - OBJECTIVE: To compare the trajectories of cognitive decline between groups with,
      and without, the later development of psychotic symptoms during Alzheimer disease
      (AD) or mild cognitive impairment (MCI). DESIGN: : The authors examined cognitive
      function in a new analysis of an existing data set, the Cardiovascular Health
      Study, an epidemiologic, longitudinal follow-up study. Our analyses examined 9
      years of follow-up data. SETTING: Community. PARTICIPANTS: The authors examined
      subjects who were without dementia at study entry, received a diagnosis of AD or
      MCI during follow-up, and had been rated on the Neuropsychiatric Inventory for
      the presence of psychosis; 362 participants for the modified Mini-Mental State
      Examination (3MS) analysis and 350 participants for the digit symbol substitution
      test (DSST) analysis had sufficient follow-up data and apolipoprotein-? (APOE)
      genotyping. MEASUREMENTS: The 3MS and DSST were administered annually and
      analyzed using mixed-effects models including APOE4 status. RESULTS: : Mean 3MS
      and DSST scores did not differ between AD with psychosis (AD + P) and without
      psychosis groups at baseline. The 3MS and DSST scores decreased more rapidly in
      subjects who ultimately developed psychosis. CONCLUSIONS: Individuals who
      ultimately develop psychosis have more rapid cognitive deterioration during the
      earliest phases of AD than individuals with AD not developing psychosis. The
      genetic and other neurobiologic factors leading to the expression of AD + P may
      exert their effects by acceleration of the neurodegenerative process.

PMID- 20808117
TI  - Late-life dementia predicts mortality beyond established midlife risk factors.
AB  - OBJECTIVES: to compare the mortality rates of elderly demented and nondemented
      subjects and the differential association of midlife risk factors with mortality
      according to dementia status. DESIGN: : Prospective historical study. SETTINGS:
      community based. PARTICIPANTS: from the 10,059 male Jewish civil servants who
      participated in the Israel Ischemic Heart Disease study in the 1960s, the 1,713
      who were evaluated for dementia in 1999/2000 and who were unequivocally
      classified as demented or nondemented. MEASUREMENTS: : Midlife sociodemographic
      and cardiovascular risk factors, late-life dementia, and mortality. RESULTS: over
      a period of 6 years, 718 (42%) subjects died. Of the 307 demented subjects, 71.8%
      died and of the 1,407 nondemented subjects, 35.4% died. Multivariate survival
      analyses showed that compared with subjects without dementia, demented subjects
      had a hazard ratio [HR] for mortality of 2.27 (95% confidence interval [CI] 1.92
      2.68). Other risk factors associated with mortality were socioeconomic status (HR
      0.94 [0.88-1.00]), higher systolic (HR 1.16 per 20 mm Hg [1.06-1.28 mm Hg]) and
      diastolic blood pressure (HR 1.15 per 10 mm Hg [1.06-1.25 mm Hg]), and ever
      smoking (HR 1.38 [1.18-1.61]). Midlife total cholesterol was not associated with
      mortality (1.01 per 40 mg/dL [0.93-1.10 mg/dL]). None of the interactions of the
      risk factors with dementia was significant. CONCLUSIONS: dementia was associated
      with more than double the risk of mortality, but this increased risk did not
      reflect exacerbation by midlife sociodemographic and cardiovascular risk factors.
      Our findings suggest that the dementing process itself or its consequences may go
      beyond well-established midlife risk factors for mortality.

PMID- 20808118
TI  - Screening and case finding tools for the detection of dementia. Part I: evidence
      based meta-analysis of multidomain tests.
AB  - AIM: To evaluate the diagnostic accuracy of all brief multidomain alternatives to
      the Mini-Mental State Examination (MMSE) in the detection of dementia. METHODS: A
      literature search, critical appraisal, and meta-analysis were conducted of robust
      diagnostic validity studies involving cognitive batteries. Twenty-nine distinct
      brief batteries were tested in 44 large-scale analyses. Twenty studies took place
      in specialist settings (11 in memory clinics and 9 in secondary care), ten
      studies were conducted in primary care, and 14 in the community. RESULTS: In
      community settings with a low prevalence of dementia, short screening methods of
      no more than 10 minutes had an overall sensitivity of 72.0% (95% confidence
      interval [CI] = 60.4%-82.3%) and a specificity of 88.2% (95% CI = 83.0%-92.5%).
      The optimal individual tests were the Telephonic interview based on MSQ, Category
      fluency/Memory impairment screen-Telephonic interview and 6 item Cognitive
      Impairment Test (6-CIT), but data were limited by the absence of multiple
      independent confirmation for any individual test. In primary care where the
      prevalence of dementia is usually modest, the optimal individual tools were the
      Abbreviated mental test score/Mental status questionnaire (MSQ), and Prueba
      cognitive de leganes (PCL). Furthermore, the Abbreviated mental test score (AMTS)
      was superior to the MMSE for case finding, but for screening the MMSE was
      optimal. If length is not a major consideration, the MMSE may remain the best
      tool for primary care clinicians who want to rule in and rule out a diagnosis. In
      specialist settings where the prevalence of dementia is often high, the optimal
      individual tools were the DEMTECT, Montreal cognitive assessment (MOCA), Memory
      Alteration test, and MINI-COG. Two tools were potentially superior to the MMSE
      for rule in and rule out, namely the 6-CIT and MINI-COG. Only four analyses
      looked specifically at accuracy in early-stage dementia, and each showed at least
      equivalent diagnostic accuracy, suggesting these methods might be applicable to
      early identification. CONCLUSION: A large number of alternatives to the MMSE have
      now been validated in large samples with favorable rule-in and rule-out accuracy.
      Evidence to date suggests for those wishing to use brief battery tests then the
      original MMSE or the AMTS should be considered in primary care and either the 6
      CIT or the MINI-COG should be considered in specialist settings.

PMID- 20808119
TI  - Antipsychotic and benzodiazepine use among nursing home residents: findings from
      the 2004 National Nursing Home Survey.
AB  - OBJECTIVES: To document the extent and appropriateness of use of antipsychotics
      and benzodiazepines among nursing home residents using a nationally
      representative survey. METHODS: Cross-sectional analysis of the 2004 National
      Nursing Home Survey. Bivariate and multivariate analyses examined relationships
      between resident and facility characteristics and antipsychotic and
      benzodiazepine use by appropriateness classification among residents aged 60
      years and older (N = 12,090). Resident diagnoses and information about behavioral
      problems were used to categorize antipsychotic and benzodiazepine use as
      appropriate, potentially appropriate, or having no appropriate indication.
      RESULTS: More than one quarter (26%) of nursing home residents used an
      antipsychotic medication, 40% of whom had no appropriate indication for such use.
      Among the 13% of residents who took benzodiazepines, 42% had no appropriate
      indication. In adjusted analyses, the odds of residents taking an antipsychotic
      without an appropriate indication were highest for residents with diagnoses of
      depression (odds ratio [OR] = 1.31; 95% confidence interval [CI]: 1.12-1.53),
      dementia (OR = 1.82; 95% CI: 1.52-2.18), and with behavioral symptoms (OR = 1.97,
      95% CI: 1.56-2.50). The odds of potentially inappropriate antipsychotic use
      increased as the percentage of Medicaid residents in a facility increased (OR =
      1.08, 95% CI: 1.02-1.15) and decreased as the percentage of Medicare residents
      increased (OR = 0.46, 95% CI: 0.25-0.83). The odds of taking a benzodiazepine
      without an appropriate indication were highest among residents who were female
      (OR = 1.44; 95% CI: 1.18-1.75), white (OR = 1.95; 95% CI: 1.47-2.60), and had
      behavioral symptoms (OR = 1.69; 95% CI: 1.41-2.01). CONCLUSION: Antipsychotics
      and benzodiazepines seem to be commonly prescribed to residents lacking an
      appropriate indication for their use.

PMID- 20808120
TI  - Impact of caregiver burden on adverse health outcomes in community-dwelling
      dependent older care recipients.
AB  - OBJECTIVE: To determine whether caregiver burden is associated with subsequent
      all-cause mortality or hospitalization among dependent community-dwelling older
      care recipients. METHODS: A prospective cohort study of 1,067 pairs of community
      dwelling 65-year-old or older care recipients and their informal caregivers was
      conducted. The 1,067 pairs completed the baseline assessment including caregiver
      burden assessed by the Zarit Burden Interview and a 3-year follow-up for all
      cause mortality and hospitalization. RESULTS: During the 3-year follow-up, 268
      recipients died and 455 were admitted to hospitals. The multivariate Cox
      proportional hazards model revealed that the recipients with caregivers with a
      baseline ZBI score in the highest quartile were 1.54 and 1.51 times more likely
      to show increased risks of all-cause mortality and hospitalization, respectively,
      in comparison with those with caregivers in the lowest quartile after adjustment
      for potential confounders. The highest quartile of caregiver burden was
      associated with all-cause mortality and hospitalization within nonusers of
      respite services including day-care services, home-help services, and nursing
      home respite stay services. No apparent association was observed within the users
      of these services except for day-care services, for which users showed a
      statistically significant association between the highest quartile and the risk
      of hospitalization. CONCLUSIONS: Heavy caregiver burden is associated with
      mortality and hospitalization among community-dwelling dependent older adults,
      even after adjusting for potential confounders. The reduction of caregiver burden
      and improvement of caregiver well-being may not only prevent the deterioration of
      caregiver health but also reduce adverse health outcomes for care recipients.

PMID- 20808121
TI  - Explicit and implicit memory in late-life depression.
AB  - OBJECTIVE: Late-life depression has been associated with memory loss and is
      frequently assumed to be a risk factor for continued cognitive decline. This
      study examined cognition in patients with late-life depression with a focus on
      the assessment of the extent and type of memory loss among elderly depressed
      patients. METHODS: Two-year cross-sectional study of elderly depressed (N = 112)
      and nondepressed (N = 138) individuals at or older than 60 years in an urban area
      surrounding a major medical center in southern California. Participants had
      little to moderate stroke risk. Volunteers were screened with the Hamilton
      Depression Rating Scale and the Structured Clinical Interview for Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I Disorders.
      Patients were diagnosed for major depression by a geriatric psychiatrist using
      DSM-IV criteria. Volunteers completed neuropsychological testing, a standard
      battery of laboratory tests, and a neurologic and psychiatric evaluation to rule
      out a medical burden that might contribute to depression or early dementia.
      RESULTS: Depressed patients showed deficits in attention and processing,
      executive function, and immediate explicit recall. Implicit learning and episodic
      recall of the testing procedure, semantic and phonetic fluency, and retention of
      newly acquired verbal material after a delay period were comparable with
      controls. CONCLUSION: Moderately depressed patients demonstrate a pattern of
      cognitive deficits suggestive of mild frontal dysfunction during recall tasks.
      Their retention of material over a delay period and their intact language skills
      indicate medial hippocampal function similar to controls. Subcortically mediated
      implicit memory is also at normal levels. These findings support current efforts
      to identify pathways of frontal and/or striatal compromise during depressive
      episodes.

PMID- 20808122
TI  - Alcohol, tobacco, and nonmedical drug use disorders in U.S. Adults aged 65 years
      and older: data from the 2001-2002 National Epidemiologic Survey of Alcohol and
      Related Conditions.
AB  - OBJECTIVES: To examine the prevalence, sociodemographic, and health-related
      correlates of substance use disorders, including alcohol, tobacco, and nonmedical
      drug use among adults aged 65 years and older. DESIGN: The 2001-2002 National
      Epidemiologic Survey on Alcohol and Related Conditions, a cross-sectional survey
      of a population-based sample. SETTING: The United States. PARTICIPANTS: Eight
      thousand two hundred five adults aged 65 years and older. MEASUREMENTS:
      Prevalence of lifetime and past 12-month Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition, determined alcohol, tobacco, and nonmedical
      drug use disorders. RESULTS: Prevalence of any substance use disorder was 21.1%
      during the lifetime and 5.4% in the past 12 months. Lifetime and past 12-month
      alcohol use disorders were 16.1% and 1.5%; tobacco use disorders were 8.7% and
      4.0%; and nonmedical drug use disorders were 0.6% and 0.2%, respectively. Younger
      age was associated with greater odds of any lifetime or past 12-month substance
      use disorders. Men and those who were divorced or separated had greater odds of
      both lifetime alcohol and tobacco use disorders. Very good or excellent self
      rated health was associated with lower odds of lifetime and past 12-month tobacco
      use disorders. Younger age and being divorced or separated were associated with
      greater odds of lifetime nonmedical drug use disorder. CONCLUSIONS: More than one
      in five older adults ever had a substance use disorder, and more than 1 in 20 had
      a disorder in the past 12 months, primarily involving alcohol or tobacco. Older
      adults have increased comorbidities and use of medications, which can increase
      risks associated with substance use.

PMID- 20808123
TI  - Depressive symptoms impair everyday problem-solving ability through cognitive
      abilities in late life.
AB  - BACKGROUND: The association between depression and functional disability in late
      life remains unclear. This study aimed to explore the relationship between
      depressive symptoms and daily functioning through the mediation of cognitive
      abilities, measured by memory, reasoning, and speed of processing. METHODS: The
      authors recruited 2,832 older adults (mean age = 73.6 years, standard deviation =
      5.9) participating in the Advanced Cognitive Training for Independent and Vital
      Elderly Study. Structural equation modeling was applied to illustrate the
      relationship between depressive symptoms and everyday problem-solving ability
      through the mediation of cognitive abilities. RESULTS: Depressive symptoms were
      associated with impaired everyday problem-solving ability directly and indirectly
      mediated through learning and memory, and reasoning. Although depressive symptoms
      were associated with speed of processing, speed of processing was not
      significantly related to everyday problem-solving ability. CONCLUSIONS: This
      study conceptualizes the possible relationships between depressive symptoms and
      daily functioning with mediation of cognitive abilities and provides a feasible
      model for the prevention of functional impairment related to geriatric depressive
      symptoms.

PMID- 20808125
TI  - One-month prevalence of mental disorders in a population sample of 95-year olds.
AB  - OBJECTIVE: To determine the 1-month prevalence of mental disorders among 95-year
      olds. DESIGN: Cross-sectional population sample of 95-year olds. SETTING: : All
      95-year olds born in the period 1901-1903 living in Gothenburg, Sweden, were
      invited. Elderly living in both community settings and nursing homes were
      included. PARTICIPANTS: In total, 338 95-year olds (response rate: 65%) were
      examined (263 women, 75 men). MEASUREMENTS: All participants were examined by
      psychiatrists using the Comprehensive Psychopathological Rating Scale and
      cognitive tests. Mental disorders were classified according to Diagnostic and
      Statistical Manual of Mental Disorders, Third Edition, Revised criteria. RESULTS:
      Two-third of all 95-year olds had a mental disorder. In the total sample of 95
      year olds, the 1-month prevalence was 52% for dementia, 8% for depression, 4% for
      anxiety, and 3% for psychotic disorders. Almost one-third (29%) of the
      nondemented 95-year olds fulfilled criteria for a psychiatric disorder: 17% had
      depression, 9% anxiety, and 7% psychotic disorder. CONCLUSIONS: The combined
      prevalence of mental disorders was high among 95-year olds, even after excluding
      dementia. These findings emphasize the importance of research, care, and
      detection of psychiatric problems in this age group.

PMID- 20808124
TI  - Executive function and short-term remission of geriatric depression: the role of
      semantic strategy.
AB  - BACKGROUND: This study tested the hypothesis that use of semantic organizational
      strategy in approaching the Mattis Dementia Rating Scale (MDRS) complex verbal
      initiation/perseveration (CV I/P) task, a test of semantic fluency, is the
      function specifically associated with remission of late-life depression. METHOD:
      Seventy elders with major depression participated in a 12-week escitalopram
      treatment trial. Neuropsychologic performance was assessed at baseline after a 2
      week drug washout period. Patients with a Hamilton Depression Rating Scale Score
      <=7 for 2 consecutive weeks and who no longer met Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition, criteria were considered to be
      remitted. Cox's proportional hazards survival analysis was used to examine the
      relationship between subtests of the I/P, other neuropsychologic domains, and
      remission rate. Participants' performance on the CV I/P subscale was coded for
      perseverations, and use of semantic strategy. RESULTS: The relationship between
      the performance on the CV I/P subscale and remission rate was significant. No
      other subtest of the MDRS I/P evidenced this association. There was no
      significant relationship between speed, confrontation naming, verbal memory, or
      perseveration with remission rate. Remitters' use of verbal strategy was
      significantly greater than nonremitters. CONCLUSIONS: Geriatric depressed
      patients who showed decrements in performance on a semantic fluency task showed
      poorer remission rates than those who showed adequate performance on this
      measure. Executive impairment in verbal strategy explained performance. This
      finding supports the concept that executive functioning exerts a "top down"
      effect on other basic cognitive processes, perhaps as a result of frontostriatal
      network dysfunction implicated in geriatric depression.

PMID- 20808126
TI  - One-year change in anterior cingulate cortex white matter microstructure:
      relationship with late-life depression outcomes.
AB  - OBJECTIVE: differences in white matter structure measured with diffusion tensor
      imaging (DTI) are associated with late-life depression, but results examining how
      these differences relate to antidepressant remission are mixed. To better
      describe these relationships, the authors examined how 1-year change in DTI
      measures are related to 1-year course of depression. DESIGN: one-year cross
      sectional follow-up to a 12-week clinical trial of sertraline. SETTING:
      outpatients at an academic medical center. PARTICIPANTS: twenty-nine depressed
      and 20 never-depressed elderly subjects. Over the 1-year period, 16 depressed
      subjects achieved and maintained remission, whereas 13 did not. MEASUREMENTS: one
      year change in fractional anisotropy (FA) and diffusivity in frontal white
      matter, as measured by DTI. RESULTS: contrary to our hypotheses, depressed
      subjects who did not remit over the study interval exhibited significantly less
      change in anterior cingulate cortex (ACC) white matter FA than did never
      depressed or depressed-remitted subjects. There were no group differences in
      other frontal or central white matter regions. Moreover, there was a significant
      positive relationship between change in Montgomery-Asberg Depression Rating Scale
      (MADRS) and change in ACC FA, wherein greater interval decline in FA was
      associated with greater interval decline in MADRS. CONCLUSION: older depressed
      individuals who remit exhibit white matter changes comparable with what is
      observed in never-depressed individuals, whereas nonremitters exhibit
      significantly less change in ACC FA. Such a finding may be related to either
      antidepressant effects on brain structure or the effects of chronic stress on
      brain structure. Further work is needed to better understand this relationship.

PMID- 20808127
TI  - Depressive symptoms in men aged 50 years and older and their relationship to
      genetic androgen receptor polymorphism and sex hormone levels in three different
      samples.
AB  - OBJECTIVE: Depression in aging men has been related to low sex hormone
      concentrations; the putatively modulating effects of the genetically determined
      androgen receptor (AR) cytosine-adenosine-guanine (CAG) repeat polymorphism are
      often not taken into account. The aim of this study was to determine how sex
      hormone levels and the AR polymorphism relate to depressive symptoms in aging
      men. METHODS: This cross-sectional study of men aged 50 years and older included
      120 consecutive patients of the Department of Psychosomatics and Psychotherapy,
      76 consecutive patients of the Andrologic Clinic, and 100 participants from the
      community sample (CS); all participants completed the Patient Health
      Questionnaire. Morning blood samples were analyzed for total and free
      testosterone, estradiol, and the AR CAG polymorphism. Patients on hormone
      substitution or other medication known to influence testosterone levels were
      excluded. RESULTS: The two clinical samples had significantly longer AR CAG
      repeats and higher depression levels compared with the CS. When controlling for
      possible confounders, depression scores were positively correlated with CAGn (r =
      0.20, df: 107, p <= 0.038) in psychosomatic patients and with CAGn (r = 0.27, df:
      55, p <= 0.043) and estradiol (r = 0.31, df: 55, p <= 0.019) in andrologic
      patients, whereas the CS showed no significant correlations between depression
      scores, CAGn, and sex hormones. CAGn did not correlate significantly with
      testosterone in the three samples. Regression analysis confirmed association of
      CAGn with depression. CONCLUSIONS: Conclusions from these data must be considered
      to be preliminary and need to be replicated. However, our results point to
      associations between the genetic AR polymorphism and vulnerability to depressive
      symptomatology.

PMID- 20808128
TI  - Cholinesterase inhibitors for Alzheimer disease: do they provide more than
      symptomatic benefits?
AB  - OBJECTIVE: This study aims to examine survival of patients with Alzheimer disease
      (AD) receiving clinical efficacy of cholinesterase inhibitors (ChEIs) and to
      compare their survival with those of patients with AD who never received ChEIs
      and cognitively intact old psychiatric outpatients. DESIGN, SETTING, AND
      PARTICIPANTS: The retrospective cohort study used national mortality data
      provided by the Korean National Statistics Office and electronic database of 15
      general hospitals on older patients who began outpatient treatment with
      psychiatric medications including ChEIs (N = 3,813). The authors controlled for
      confounding by using multivariate models and propensity scoring methods.
      MEASUREMENTS: Mortality rate of patients with AD receiving ChEIs was compared
      with those of patients with AD who never received ChEIs and cognitively intact
      old psychiatric outpatients. RESULTS: Observed additional survival of patients
      with AD receiving ChEIs (mortality rate: 13.1%), when compared with patients with
      AD who never received ChEIs (15.4%) was not statistically significant (p = 0.74;
      hazard ratio [HR]: 1.03, 95% confidence interval [CI]: 0.67-1.59). Patients with
      AD receiving ChEIs showed higher mortality rate (13.1%) compared with that of
      cognitively intact old psychiatric outpatients (8.6%) (p <0.001; HR: 1.60, 95%
      CI: 0.96-2.68). CONCLUSION: This study does not support that ChEIs increase
      survival of patients with AD, compared with patients with AD who have never
      treated with ChEIs. Therefore, all ChEIs should be considered for symptomatic use
      only and not to be capable of modifying mortality of patients with AD.

PMID- 20808130
TI  - Specific anatomic associations between white matter integrity and cognitive
      reserve in normal and cognitively impaired elders.
AB  - OBJECTIVES: to investigate the associations between white matter (WM) integrity
      and cognitive reserve (CR) in healthy elders (HE), amnestic mild cognitive
      impairment (a-MCI), and Alzheimer's disease (AD). The authors studied
      correlations between CR and WM integrity in regions showing WM age-related
      effects or pathologic changes and tested the differences of slopes between
      groups. METHODS: diffusion tensor images (DTIs) were obtained from 18 young
      individuals, 15 HE, 16 a-MCI cases, and 15 AD cases. Tract-based spatial
      statistics was used to process DTI data. Areas showing age-related fractional
      anisotropy (FA) shrinkages (HE < young) and pathology-related FA network "(AD <
      HE)" were defined. Correlations between CR and WM integrity were adjusted for
      age, gender, memory performance and brain volumes. RESULTS: he presented more
      negative correlations between CR and WM integrity than patients with a-MCI and AD
      in age-related areas, such as the genum of the corpus callosum. However, these
      results were mediated by normal variability in memory function and brain volumes.
      For patients with a-MCI, negative associations between CR and FA were found in
      several major tracts, being more robust than in AD group. Although longitudinal
      results need to be interpreted with caution because of the reduced sample of
      patients with MCI, after 2 years of follow-up, all patients who progressed to AD
      had high-CR scores, suggesting a putative link between reduced WM integrity
      (maximal in patients with high CR) and risk of progression to AD. CONCLUSIONS: CR
      correlates are implemented in different anatomic WM areas in HE and patients with
      a-MCI. Healthy elders with high CR may present better tolerance of typical age
      related effects on WM integrity; in patients with a-MCI, the association may
      reflect increased capacity to cope with incipient cerebral damage.

PMID- 20808129
TI  - The effect of cognitive impairment on mental healthcare costs for individuals
      with severe psychiatric illness.
AB  - OBJECTIVE: This study was conducted to determine the effect of cognitive
      impairment (CI) on mental healthcare costs for older low-income adults with
      severe psychiatric illness. METHODS: Data were collected from 62 ethnically
      diverse low-income older adults with severe psychiatric illness who were
      participating in day programming at a large community mental health center. CI
      was diagnosed by a neuropsychologist utilizing the Mattis Dementia Rating Scale
      Second Edition and structured ratings of functional impairment (Clinical Dementia
      Rating Scale). Mental healthcare costs for 6, 12, and 24-month intervals before
      cognitive assessments were obtained for each participant. Substance abuse history
      was evaluated utilizing a structured questionnaire, depression symptom severity
      was assessed utilizing the Hamilton Depression Rating Scale, and psychiatric
      diagnoses were obtained through medical chart abstraction. RESULTS: CI was
      exhibited by 61% of participants and was associated with significantly increased
      mental healthcare costs during 6, 12, and 24-month intervals. Results of a
      regression analysis indicated that ethnicity and CI were both significant
      predictors of log transformed mental healthcare costs over 24 months with CI
      accounting for 13% of the variance in cost data. CONCLUSIONS: CI is a significant
      factor associated with increased mental healthcare costs in patients with severe
      psychiatric illness. Identifying targeted interventions to accommodate CI may
      lead to improving treatment outcomes and reducing the burden of mental healthcare
      costs for individuals with severe psychiatric illness.

PMID- 20808131
TI  - Effect of benzodiazepine discontinuation on dementia risk.
AB  - OBJECTIVES: This study aimed to examine whether benzodiazepine (BZD)
      discontinuation would decrease the risk of dementia. DESIGN: A population-based
      nested case-control study of dementia was used. SETTING: All subjects aged 45
      years or older and enrolled in the National Health Insurance Research Database in
      Taiwan between 1997 and 2007 were randomly selected. PARTICIPANTS: A total of
      8,434 cases had been identified with dementia at least three times in ambulatory
      claims or with one record in inpatient claims. They were individually matched
      with two comparison subjects (N = 16,706) by age, gender, and index date.
      MEASUREMENTS: The lengths of discontinuation, cumulative BZD dose, and potential
      confounding factors, including medical and psychiatric disorders, were measured
      and used for further analysis. RESULTS: Compared with nonusers, current users had
      an increased risk of dementia (adjusted odds ratio [aOR] = 2.71; 95% confidence
      interval [CI], 2.46-2.99). The dementia risk for former users was reduced as the
      duration of discontinuation lengthened (<1 month aOR = 2.40, 95% CI, 1.98-2.92; 1
      3 months aOR = 1.93, 95% CI, 1.67-2.23; 3-6 months aOR = 1.49, 95% CI, 1.28-1.74;
      6-12 months aOR = 1.43, 95% CI, 1.25-1.64; 1-2 years aOR = 1.23, 95% CI, 1.09
      1.40; 2-3 years aOR = 1.22, 95% CI, 1.06-1.40; and >3 years aOR = 1.08, 95% CI,
      0.98-1.20). The decreasing trend was significant (p < 0.001). CONCLUSION: The
      risk of dementia was high for current users and decreased as the duration of BZD
      discontinuation lengthened. Further investigations are needed to replicate this
      association and explore the underlying mechanism that links long-term BZD use,
      BZD discontinuation, and the pathogenesis of neurocognitive dysfunction.

PMID- 20808133
TI  - Association study of interferon-gamma, cytosolic phospholipase A2, and
      cyclooxygenase-2 gene polymorphisms in Alzheimer disease.
AB  - OBJECTIVE: The increased production of proinflammatory mediators such as
      cytokines and prostaglandins may interact at multiple levels with
      neurodegeneration in Alzheimer disease (AD). This study was undertaken to
      evaluate the possible role of interferon-gamma (IFN-gamma) T+874A, cytoplasmic
      phospholipase A2 (cPLA2) BanI, and cyclooxygenase-2 (COX-2) G-765C polymorphisms
      in AD. METHODS: The study included 237 probable patients with AD who met the
      diagnostic criteria of National Institute of Neurological and Communicative
      Disorders and Stroke-AD and Related Disorders Association, and 245 probands in
      the healthy comparison (HC) group. RESULTS: No significant difference in mean age
      or in the distribution of genders between AD and HC groups was found. The COX-2
      G/G genotype was significantly more frequent in the AD, when compared with the HC
      group. There was no significant correlation between IFN-gamma or cPLA2 genotypes
      and AD. CONCLUSIONS: Our findings indicate that the COX-2 G/G genotype is
      associated with AD and support the involvement of COX-2 in AD etiology.

PMID- 20808132
TI  - Depression in Parkinson's disease: symptom improvement and residual symptoms
      after acute pharmacologic management.
AB  - OBJECTIVE: Parkinson's disease (PD) is frequently complicated by depression and
      there is a paucity of controlled research that can inform the management of this
      disabling nonmotor complaint. A randomized controlled trial of nortriptyline,
      paroxetine, and placebo for the treatment of depression in PD (dPD) was recently
      completed. The purpose of this article is to describe the baseline pattern of
      depressive symptom presentation in PD, the specific symptoms of dPD that improve
      with pharmacotherapy, and the residual symptoms that remain in patients who meet
      a priori criteria for response or remission after acute treatment (8 weeks).
      SETTING: The Departments of Psychiatry and Neurology at Robert Wood Johnson
      Medical School, New Jersey. PARTICIPANTS: : Fifty-two depressed patients (major
      depression or dysthymia based on Diagnostic and Statistical Manual of Mental
      Disorders 4th edition criteria) with Parkinson's disease (by research criteria).
      DESIGN/INTERVENTION: A randomized controlled trial of nortriptyline, paroxetine,
      and placebo. MEASUREMENT: The four subscales (core mood, anxiety, insomnia, and
      somatic) and individual items from the Hamilton Rating Scale for Depression-17
      were the focus of this study. These measures were assessed at baseline and Week
      8. RESULTS: Baseline depressive symptoms were unrelated to motor functioning.
      Treatment response was associated with significant improvements in the core mood,
      anxiety, insomnia, and somatic symptoms seen in dPD. Residual symptoms, such as
      sadness and loss of interest, persisted in treatment responders in a milder form
      than was initially present. CONCLUSIONS: Antidepressants may influence all
      symptoms of dPD, including those that share great overlap with the physical
      disease process. Additional research regarding adjunctive interventions is needed
      to help optimize the management of dPD.

PMID- 20808134
TI  - How much striving is too much? John Henryism active coping predicts worse daily
      cortisol responses for African American but not white female dementia family
      caregivers.
AB  - INTRODUCTION: The John Henryism active coping (JHAC) hypothesis suggests that
      striving with life challenges predicts increased risk for cardiovascular disease
      for those with scarce coping resources. This study examined the moderating role
      of JHAC in the associations of 1) caregiver status and 2) care recipient
      functional status with diurnal salivary cortisol patterns among 30 African
      Americans (AAs) and 24 white female dementia caregivers and 63 noncaregivers (48
      AAs). METHODS: Caregiver participants completed the JHAC-12 scale, Activities of
      Daily Living (ADL) scale, and Revised Memory and Behavior Problem checklist
      (RMBPC) and collected five saliva samples daily (at awakening, 9 A.M., 12 P.M., 5
      P.M., and 9 P.M.) for 2 successive days. RESULTS: Univariate analysis of variance
      tests with mean diurnal cortisol slope as the outcome illustrated that among AA
      caregivers, higher JHAC scores were related to flatter (or more dysregulated)
      cortisol slopes. The JHAC by ADL and JHAC by RMBPC interactions were each
      significant for AA caregivers. Among AA caregivers who reported higher ADL and
      RMBPC scores, higher JHAC scores were associated with flatter cortisol slopes.
      CONCLUSIONS: These findings extend recent studies by showing that being AA, a
      caregiver, and high in JHAC may elevate the risk for chronic disease, especially
      for those with higher patient ADL and behavioral problems. Thus, it is imperative
      that interventions appreciate the pernicious role of high-effort coping style,
      especially for AA caregivers, to minimize the stressful side effects of patient
      ADL and memory and behavioral problems for the caregiver.

PMID- 20808136
TI  - The built environment and depression in later life: the health in men study.
AB  - OBJECTIVE: This study examined the impact of built environment (BE) attributes on
      depression in older men to determine whether associations were independent of
      neighborhood composition factors and sociodemographic, psychosocial, and health
      factors at the individual level. METHODS: The authors used geocoded data from the
      Health in Men Study collected in Western Australia in 2001 (N = 5,218).
      Depression was measured using the self-rated 15-item Geriatric Depression Scale.
      Geographic Information Systems were used to objectively measure BE attributes.
      Univariate logistic regressions were applied to select relevant covariates.
      Multivariate logistic regressions were conducted to examine BE attributes both
      separately and conjointly. RESULTS: Higher degrees of land-use mix were
      associated with higher odds of depression independent of other factors, including
      street connectivity and residential density (odds ratio = 1.54, 95% confidence
      interval [CI] = 1.10-2.16, and odds ratio = 1.52, 95% CI = 1.08-2.14 for the
      second and third tertiles, respectively). Further examination showed that retail
      availability was associated with a 40% increase in the odds of depression (95% CI
      = 4%-90%) independent of other factors, including availability of other land
      uses. CONCLUSIONS: The BE is independently associated with depression through
      land-use mix, and specifically through retail availability. Although local retail
      facilitates walking, our findings suggest that it may increase the odds of
      depression in older men. This requires further exploration but suggests the need
      for careful planning of retail in residential environments, particularly near
      housing for older adults.

PMID- 20808135
TI  - Demographic, neuropsychological, and functional predictors of rate of
      longitudinal cognitive decline in Hispanic older adults.
AB  - OBJECTIVE: The identification of older adults who are at increased risk of future
      cognitive decline is often difficult, particularly in individuals of an ethnic
      minority. This study evaluated which baseline demographic, neuropsychological,
      and functional variables were most strongly associated with future longitudinal
      decline in global cognitive function. DESIGN/SETTING: Participants were part of a
      community-based prospective longitudinal study of 1,789 older Hispanics
      (Sacramento Area Latino Study on Aging). PARTICIPANTS: A subsample of 639
      individuals was evaluated, comprising cognitively normal, mildly impaired, and
      dementia cases, and were followed longitudinally for up to 7 years. Sixty-three
      percent were tested in Spanish. MEASUREMENTS: Latent growth curve modeling of
      longitudinal data was used to assess the effects of age, gender, education,
      language of test administration (Spanish or English), acculturation, baseline
      measures of neuropsychological function (i.e., verbal memory and confrontation
      naming), and baseline everyday functioning (as measured by the Informant
      Questionnaire on Cognitive Decline in the Elderly) on rate of change in global
      cognitive impairment (measured by the 3MS). RESULTS: Less education, being tested
      in English, and poorer scores on the neuropsychological tests were all cross
      sectionally associated with lower baseline 3MS scores. However, longitudinal
      decline in global cognition over time was primarily associated with older age and
      poorer everyday function at baseline. CONCLUSIONS: Informant-based ratings of
      functional impairment, which are easy to collect in a clinical setting, have
      significant use in identifying Hispanic older adults at increased risk for future
      cognitive decline.

PMID- 20808137
TI  - Social functioning among older community-dwelling patients with schizophrenia: a
      review.
AB  - Social dysfunction is a hallmark of schizophrenia and a major constituent of its
      burden of disease. There is a need for more data on social functioning of older
      schizophrenic patients, because their numbers are rapidly growing and most are
      residing within the community. This article reviews existing evidence on social
      functioning in community-dwelling schizophrenic patients older than 55 years,
      focusing on social roles, social support, and social skills. Thirty-six
      publications proved fit for inclusion in the review. Studies from outside the
      United States were underrepresented. The available data suggest that the majority
      of older schizophrenic patients are well behind their healthy age-peers with
      respect to various aspects of social functioning. At the same time, a
      considerable heterogeneity among patients can be found. Cognitive abilities
      feature as a factor of major impact on social functioning, outweighing clinical
      symptoms. When evaluating social functioning both objective and subjective
      appraisals should be taken into account, because they may highlight different
      aspects of social functioning. Social support, impact of gender, and specific
      characteristics of older-old patients figure among areas that should be given
      priority in future research of social functioning in late life schizophrenia.

PMID- 20808138
TI  - Decreased default mode neural modulation with age in schizophrenia.
AB  - OBJECTIVE: Previous studies have shown that patients with schizophrenia have less
      modulation of the task-positive and default mode neural networks during novelty
      detection. The diminished modulation may be interpreted as less functional
      activation of the task-positive network and less functional deactivation of the
      default mode network. The relationship between network modulation and age has not
      been assessed in patients with a long duration of illness. METHOD: Seventeen
      patients with schizophrenia (age range, from 34 to 60 years) with minimum
      disorder duration of 15 years and 28 demographically similar comparison subjects
      (age range, from 36 to 58 years) from the Mind Clinical Imaging Consortium
      database completed the auditory oddball discrimination task. Independent
      component analysis identified temporally cohesive but spatially distributed
      neural networks. RESULTS: Group membership (F[1, 41] = 7.17, p = 0.011) and the
      interaction of group and age (F[1, 41] = 6.92, p = 0.012) affected the modulation
      of the anterior default mode network. Duration of illness was also significantly
      related to the modulation of the anterior default mode network (t[2, 15] = 2.24,
      p <0.042). These results were selective for the anterior default mode network and
      were not replicated with the posterior default mode network. CONCLUSIONS: These
      findings show evidence of changes in the temporal modulation of the anterior
      default mode network with age and duration of illness in patients with
      schizophrenia. The loss of negative modulation of the anterior default mode
      network suggests that neural functions in schizophrenia may not be "static" later
      in the disease course.

PMID- 20808139
TI  - The relationship of cardiovascular risk factors to Alzheimer disease in Choctaw
      Indians.
AB  - OBJECTIVES: To test the hypothesis that cardiovascular risk factors (CRFs)
      influence predisposition to and the clinical course of Alzheimer disease (AD),
      the authors compared Choctaw Indians, a group with known high CRF with white
      persons with AD. In addition to CRF history, the authors investigated the
      frequency of apolipoprotein E4 (apoE4) genotype andplasma homocysteine (HC)
      levels. METHOD: The authors compared 39 Choctaw Indians with AD and 39 Choctaw
      Indians without AD to 39 white persons with AD with all groups similar in age.
      CRF history included diabetes, hypertension, high cholesterol or hypolipidemic
      agent use, or myocardial infarction. The authors also compared plasma HC
      concentration and apoE4 allele frequency. RESULTS: Choctaw persons with AD
      differed significantly from white persons with AD in history of hypertension,
      diabetes, and in HC values but not from Indians without AD. There was a
      significantly lower apoE4 allele frequency in Choctaw Indian AD than white
      persons with AD, and both AD groups had an affected first degree relative
      significantly more often than Indian controls. There was no relationship between
      the number of CRF and age at onset among Indians or whites, whereas HC
      concentration was associated with significantly earlier age of onset for Choctaw
      Indians but not for whites. CONCLUSIONS: This small study suggests that in
      Choctaw Indians modifiable risk factors may play more of a role in disease
      pathogenesis than in whites and that nonmodifiable risk factors such as apoE4 may
      play less of a role.

PMID- 20808140
TI  - Cognitive decline in patients with dementia as a function of depression.
AB  - OBJECTIVE: There is evidence that major depression increases the risk for
      dementia, but there is conflicting evidence as to whether depression may
      accelerate cognitive decline in dementia. The authors tested the hypothesis that
      decline in cognitive function over time is more pronounced in patients with
      dementia with comorbid depression, when compared with patients with dementia
      without depression history. DESIGN: Prospective, longitudinal cohort study of
      aging. SETTING: Nursing home. PARTICIPANTS: Three hundred thirteen elderly
      nursing home residents (mean age at baseline: 86.99 years, standard deviation =
      6.7; 83.1% women). At baseline, 192 residents were diagnosed with dementia, and
      another 27 developed dementia during follow-up. Thirty residents suffered from
      major depression at any point during the study, and 48 residents had a history of
      depression. MEASUREMENTS: The authors measured cognitive decline using change in
      Mini-Mental State Examination (MMSE) scores over up to 36 months. The authors
      calculated multilevel regression models to estimate the effects of age, gender,
      education, dementia status, depression, depression history, and an interaction
      between dementia and depression, on change in MMSE scores over time. RESULTS:
      Beyond the effects of age, gender, and education, residents showed steeper
      cognitive decline in the presence of dementia (beta = -13.69, standard error =
      1.38) and depression (beta = -4.16, SE = 1.2), which was further accelerated by
      the presence of both depression and dementia (beta = -2.72, SE = 0.65).
      CONCLUSIONS: In dementia, the presence of depression corresponds to accelerated
      cognitive decline beyond gender and level of education, suggesting a unique
      influence of depression on the rate of cognitive decline in dementia.

PMID- 20808141
TI  - Age group differences among veterans enrolled in a clinical service for
      behavioral health issues in primary care.
AB  - OBJECTIVES: : To examine age group differences in the identification, engagement,
      clinical outcomes, and monitoring of older, relative to middle aged and younger,
      veterans with behavioral health needs enrolled in an integrated care management
      program DESIGN: : Cross-sectional and longitudinal SETTING: : Primary care
      clinics affiliated with two Veterans Affairs Medical Centers PARTICIPANTS: : A
      total of 9,087 veterans were referred to the Behavioral Health Laboratory (BHL)
      for a behavioral health assessment and 7,251 completed an initial assessment
      MEASUREMENTS: : Data on consult source and reason for the referral, clinical
      assessment outcomes, and engagement were collected during a 3-year period.
      Variations in process and patient-level factors were examined as a function of
      age group. RESULTS: : Although all age groups evidenced high rates of engagement
      in clinical assessment calls, older adults were slightly more likely to complete
      the assessments than young/middle-aged veterans. Clinical assessment outcomes
      revealed that although older adults were less likely to meet criteria for more
      complex, severe conditions, rates of disorder remained clinically significant,
      and comorbidity was common. Finally, older veterans receiving treatment
      monitoring for a newly prescribed antide- pressant consistently reported high
      rates of antidepressant adherence during the course of the monitoring calls and
      showed significant reductions in depressive symptomatology during the course of
      monitoring. CONCLUSIONS: : Results indicate age-related variability in processes
      and outcomes among veterans referred to the BHL and suggest that older veterans
      are just as likely to benefit from a program designed to facilitate the
      identification, engagement, monitoring, and care management of primary care
      patients experiencing behavioral health issues.

PMID- 20808142
TI  - Physical activity and Alzheimer disease course.
AB  - OBJECTIVES: To examine the association between physical activity (PA) and
      Alzheimer disease (AD) course. BACKGROUND: PA has been related to lower risk for
      AD. Whether PA is associated with subsequent AD course has not been investigated.
      METHODS: In a population-based study of individuals aged 65 years and older in
      New York who were prospectively followed up with standard neurologic and
      neuropsychological evaluations (every ~1.5 years), 357 participants i) were
      nondemented at baseline and ii) were diagnosed with AD during follow-up (incident
      AD). PA (sum of participation in a variety of physical activities, weighted by
      the type of activity [light, moderate, and severe]) obtained 2.4 (standard
      deviation [SD], 1.9) years before incidence was the main predictor of mortality
      in Cox models and of cognitive decline in generalized estimating equation models
      that were adjusted for age, gender, ethnicity, education, comorbidities, and
      duration between PA evaluation and dementia onset. RESULTS: One hundred fifty
      incident AD cases (54%) died during the course of 5.2 (SD, 4.4) years of follow
      up. When compared with incident AD cases who were physically inactive, those with
      some PA had lower mortality risk, whereas incident AD participants with much PA
      had an even lower risk. Additional adjustments for apolipoprotein genotype,
      smoking, comorbidity index, and cognitive performance did not change the
      associations. PA did not affect rates of cognitive or functional decline.
      CONCLUSION: Exercise may affect not only risk for AD but also subsequent disease
      duration: more PA is associated with prolonged survival in AD.

PMID- 20808144
TI  - The future of dementia: a case of hardening of the categories.

PMID- 20808143
TI  - (99m)Tc hexamethyl-propylene-aminoxime single-photon emission computed tomography
      prediction of conversion from mild cognitive impairment to Alzheimer disease.
AB  - OBJECTIVE: To examine the utility of single-photon emission computed tomography
      (SPECT) to predict conversion from mild cognitive impairment (MCI) to Alzheimer
      disease (AD). DESIGN: Longitudinal, prospective study. SETTING: University-based
      memory disorders clinic. PARTICIPANTS: One hundred twenty seven patients with MCI
      and 59 healthy comparison subjects followed up for 1-9 years. MEASUREMENTS:
      Diagnostic evaluation, neuropsychological tests, social/cognitive function,
      olfactory identification, apolipoprotein E genotype, magnetic resonance imaging,
      and brain Tc hexamethyl-propylene-aminoxime SPECT scan with visual ratings, and
      region of interest (ROI) analyses were done. RESULTS: Visual ratings of SPECT
      temporal and parietal blood flow did not distinguish eventual MCI converters to
      AD (N = 31) from nonconverters (N = 96), but the global rating predicted
      conversion (41.9% sensitivity and 82.3% specificity, Fisher's exact test p =
      0.013). Blood flow in each ROI was not predictive, but when dichotomized at the
      median value of the patients with MCI, low flow increased the hazard of
      conversion to AD for parietal (hazard ratio: 2.96, 95% confidence interval: 1.16
      7.53, p = 0.023) and medial temporal regions (hazard ratio: 3.12, 95% confidence
      interval: 1.14-8.56, p = 0.027). In the 3-year follow-up sample, low parietal (p
      <0.05) and medial temporal (p <0.01) flow predicted conversion to AD, with or
      without controlling for age, Mini-Mental State Examination, and apolipoprotein E
      epsilon4 genotype. These measures lost significance when other strong predictors
      were included in logistic regression analyses: verbal memory, social/cognitive
      functioning, olfactory identification deficits, hippocampal, and entorhinal
      cortex volumes. CONCLUSIONS: SPECT visual ratings showed limited utility in
      predicting MCI conversion to AD. The modest predictive utility of quantified low
      parietal and medial temporal flow using SPECT may decrease when other stronger
      predictors are available.

PMID- 20808145
TI  - Goal-oriented cognitive rehabilitation for people with early-stage Alzheimer
      disease: a single-blind randomized controlled trial of clinical efficacy.
AB  - OBJECTIVES: To provide evidence regarding the clinical efficacy of cognitive
      rehabilitation (CR) in early-stage Alzheimer disease (AD). DESIGN: Single-blind
      randomized controlled trial comparing CR with relaxation therapy and no
      treatment. SETTING: Outpatient, community-based setting. PARTICIPANTS: Sixty-nine
      individuals (41 women, 28 men; mean age 77.78 years, standard deviation 6.32,
      range = 56-89) with a diagnosis of AD or mixed AD and vascular dementia and a
      Mini-Mental State Examination score of 18 or above, and receiving a stable dose
      of acetylcholinesterase-inhibiting medication. Forty-four family carers also
      contributed. INTERVENTION: Eight weekly individual sessions of CR consisting of
      personalized interventions to address individually relevant goals supported by
      components addressing practical aids and strategies, techniques for learning new
      information, practice in maintaining attention and concentration, and techniques
      for stress management. MEASUREMENTS: The primary outcomes were goal performance
      and satisfaction, assessed using the Canadian Occupational Performance Measure.
      Questionnaires assessing mood, quality of life and career strain, and a brief
      neuropsychological test battery were also administered. A subset of participants
      underwent functional magnetic resonance imaging (fMRI). RESULTS: CR produced
      significant improvement in ratings of goal performance and satisfaction, whereas
      scores in the other two groups did not change. Behavioral changes in the CR group
      were supported by fMRI data for a subset of participants. CONCLUSIONS: The
      findings support the clinical efficacy of CR in early-stage AD. CR offers a means
      of assisting people with early-stage AD and their families in managing the
      effects of the condition.

PMID- 20808147
TI  - Integrative psychotherapeutic nursing home program to reduce multiple psychiatric
      symptoms of cognitively impaired patients and caregiver burden: randomized
      controlled trial.
AB  - OBJECTIVE: To test the effectiveness of an integrative psychotherapeutic nursing
      home program (integrative reactivation and rehabilitation [IRR]) to reduce
      multiple neuropsychiatry symptoms (MNPS) of cognitively impaired patients and
      caregiver burden (CB). DESIGN: Randomized controlled trial. SETTING: Psychiatric
      skilled nursing home (IRR) and usual care (UC), consisting of different types of
      nursing home care at home or in an institution. PARTICIPANTS: N = 168 (81 IRR and
      87 UC). Patients had to meet classification of the Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition for dementia, amnestic disorders, or
      other cognitive disorders. Further inclusion criteria: Neuropsychiatric Inventory
      (NPI) >=3; Mini-Mental State Examination >=18 and <=27; and Barthel Index (BI)
      >=5 and <=19. INTERVENTION: IRR consisted of a person-oriented integrative
      psychotherapeutic nursing home program to reduce MNPS of the patient and CB. UC
      consisted of different types of nursing home care at home or in an institution,
      mostly emotion oriented. MEASUREMENTS: Primary outcome variable was MNPS (number
      and sum-severity of NPI). Furthermore, burden and competence of caregiver were
      also measured. ASSESSMENTS: T1 (inclusion), T2 (end of treatment), T3 (after 6
      months of follow-up). Cohen's d (Cd) was calculated for mean differences
      (intention to treat). For confounding, repeated measurement modeling (random
      regression modeling [RRM]) was applied. RESULTS: In the short term from the
      perspective of the caregiver, IRR showed up to 34% surplus effects on MNPS of the
      patients; NPI symptoms: 1.31 lower (Cd, -0.53); and NPI sum- severity: 11.16
      lower (Cd, -0.53). In follow-up, the effects were sustained. However, from the
      perspective of the nursing team, these effects were insignificant, although the
      trend was in the same direction and correlated significantly with the caregiver
      results over time (at T3: r = 0.48). In addition, IRR showed surplus effects (up
      to 36%) on burden and competence of caregiver: NPI emotional distress: 3.78 (Cd, 
      0.44); CB: 17.69 (Cd, -0.63) lower; and Competence: 6.26 (Cd, 0.61) higher. In
      follow-up, the effects increased up to 50%. RRM demonstrated that the effects
      were stable. CONCLUSION: From the perspective of the caregiver, IRR was
      significantly more effective than UC to reduce MNPS in cognitively impaired
      patients and CB. In follow-up, the effect on CB even increased. However, from the
      perspective of the nursing team, the effects on MNPS were statistically
      insignificant. Nevertheless, the trend was in the same direction and correlated
      significantly with the caregiver results over time. Further research is needed,
      preferably using a blinded randomized controlled trial.

PMID- 20808148
TI  - Neurocognitive dysfunction associated with sleep quality and sleep apnea in
      patients with mild cognitive impairment.
AB  - OBJECTIVES: Sleep apnea syndrome (SAS) is considered a risk factor for cognitive
      decline in the elderly. The specific neurocognitive decline has been suggested as
      a predictive factor for dementia in patients with mild cognitive impairment
      (MCI). The authors aim to illustrate the sleep characteristics related to the
      specific neurocognitive decline in the community-dwelling elderly including
      patients with MCI. DESIGN: Cross-sectional. SETTINGS: Center for sleep and
      chronobiology in Kangwon National University Hospital. PARTICIPANTS: Thirty
      patients with MCI and 30 age- and sex-matched normal elderly subjects were
      selected. MEASUREMENTS: The authors administered seven tests in the Korean
      version of the Consortium to Establish A Registry of Alzheimer's Disease
      Neuropsychological battery and conducted nocturnal polysomnography. A p value
      below 0.05 was considered a statistical significance. RESULTS: There was no
      significant difference in sleep parameters between the MCI and normal comparison
      (NC) groups. Sleep efficiency was positively correlated with Constructional
      Recall (CR) scores in both NC and MCI groups (r = 0.393 and 0.391, respectively).
      The amount of slow wave sleep (SWS) was also positively correlated with Boston
      naming test (BNT) scores in both groups (r = 0.392, 0.470, respectively).
      Stepwise multiple regression models showed that SWS and the apnea index were
      significant independent variables associated with the BNT score (Deltabeta = 0.43
      and -0.34, respectively; adjusted R = 0.298) in the MCI group, and the amount of
      rapid eye movement sleep was a significant independent variable associated with
      the CR score (Deltabeta = 0.49; adjusted R = 0.217) in the NC group. CONCLUSIONS:
      Our results show that poor sleep quality and greater severity of SAS were
      associated with impaired language function reflecting frontal-subcortical
      pathology in patients with MCI. This suggests that vulnerability to a specific
      brain damage associated with SAS could increase the risk for dementia.

PMID- 20808146
TI  - Elevated cortisol in older adults with generalized anxiety disorder is reduced by
      treatment: a placebo-controlled evaluation of escitalopram.
AB  - BACKGROUND: Generalized anxiety disorder (GAD) is a common disorder in older
      adults, which has been linked to hyperactivity of the hypothalamic-pituitary
      adrenal (HPA) axis in this age group. The authors examined whether treatment of
      GAD in older adults with a selective serotonin reuptake inhibitor (SSRI) corrects
      this HPA axis hyperactivity. METHODS: The authors examined adults aged 60 years
      and older with GAD in a 12-week randomized controlled trial comparing the SSRI
      escitalopram with placebo. The authors collected salivary cortisol at six daily
      time points for 2 consecutive days to assess peak and total (area under the
      curve) cortisol, both at baseline and posttreatment. RESULTS: Compared with
      placebo-treated patients, SSRI-treated patients had a significantly greater
      reduction in both peak and total cortisol. This reduction in cortisol was limited
      to patients with elevated (above the median) baseline cortisol, in whom SSRI
      treated patients showed substantially greater reduction in cortisol than did
      placebo-treated patients. Reductions in cortisol were associated with
      improvements in anxiety. Additionally, genetic variability at the serotonin
      transporter promoter predicted cortisol changes. CONCLUSIONS: SSRI treatment of
      GAD in older adults reduces HPA axis hyperactivity. Further research should
      determine whether these treatment-attributable changes are sustained and
      beneficial.

PMID- 20808149
TI  - Schizophrenia in later life: emerging from the shadows.

PMID- 20808150
TI  - Comparing the influences of age and disease on distortion in the clock drawing
      test in Japanese patients with schizophrenia.
AB  - OBJECTIVE: The Clock Drawing Test (CDT) is commonly used for cognitive screening,
      but there are few studies that compare performance on the CDT among schizophrenic
      patients of different ages. The objective of this study was to investigate the
      influence of schizophrenia and aging on performance in the CDT. METHOD:
      Schizophrenic patients (N = 244) and a comparison group (N = 875) were recruited
      as subjects. Freedman's CDT was completed by all subjects, and the influences of
      disease and aging on performance in the CDT were examined. Multiple comparisons
      of the CDT scores between patients and the comparison group and within three age
      subgroups (young: less than 40 years, middle aged: 40-59 years, elderly: more
      than 60 years) were performed. RESULTS: There was a significant interaction of
      diagnosis and age, and the education significantly influenced the total score for
      all CDT conditions. For almost all age subgroups of patients, individuals with
      schizophrenia had significantly lower scores on all the CDT conditions than did
      the comparison group subjects. For patients and the comparison group, the elderly
      subgroup performed significantly worse than the young and middle-aged subgroups
      on almost all conditions of the CDT. Qualitative analysis of the clocks drawn
      revealed that the number of CDT categories in which schizophrenic patients scored
      significantly lower than the comparison group tended to increase with aging
      across both groups. CONCLUSIONS: This study suggests that performance on the CDT
      was impaired not only by disease but also by aging. The study confirms that the
      CDT is sensitive enough to screen for cognitive impairments in schizophrenia.

PMID- 20808151
TI  - How effective is bibliotherapy for very old adults with subthreshold depression?
      A randomized controlled trial.
AB  - OBJECTIVES: Depressive symptoms are common among elderly primary care patients,
      and because they encounter considerable barriers in seeking help and they often
      resist referral to specialized mental health facilities, it is important to look
      for easily accessible interventions within the primary care setting.
      Bibliotherapy, which has been found to be effective among younger populations,
      might be an attractive option. In this study, the authors investigated the
      effectiveness of bibliotherapy for depressive symptomatology in very old adults.
      DESIGN: Randomized controlled trial. After a 3-month period of "watchful
      waiting," the participants were randomly assigned to a bibliotherapy group or a
      usual care group. SETTING: Thirty-three general practices in the north-western
      region of the Netherlands. PARTICIPANTS: One hundred seventy community-dwelling
      adults, aged 75 and older, with subthreshold depression. INTERVENTION: The
      bibliotherapy intervention consisted of an information leaflet and a self-help
      manual "Coping with Depression" adapted for the elderly. MEASUREMENTS: Outcome
      measures after 3 months were a) change in depressive symptoms according to the
      Center for Epidemiologic Studies Depression Scale (CES-D) and b) the proportion
      of participants who scored a significant improvement on the CES-D. RESULTS: One
      hundred forty-six (85.9%) of the 170 participants completed the baseline and
      follow-up measurements. The authors did not find any clinically relevant and
      statistically significant differences between the intervention group and the
      control group in the severity of the depressive symptoms. CONCLUSION:
      Bibliotherapy as a stand-alone intervention for the elderly (aged 75 years and
      older) did not reduce depressive symptoms more than usual care. This might
      indicate that bibliotherapy can only be effective for patients who are motivated
      and acknowledge their depression.

PMID- 20808152
TI  - Beyond the dawning of the age of biomarkers.

PMID- 20808154
TI  - Current world literature. Neuromuscular diseases: muscle. Nerve, neuromuscular
      junction and motor neuron diseases.

PMID- 20808156
TI  - Current world literature.

PMID- 20808157
TI  - AACVPR/ACCF/AHA 2010 Update: Performance measures on cardiac rehabilitation for
      referral to cardiac rehabilitation/secondary prevention services: A report of the
      American Association of Cardiovascular and Pulmonary Rehabilitation and the
      American College of Cardiology Foundation/American Heart Association Task Force
      on Performance Measures (Writing Committee to Develop Clinical Performance
      Measures for Cardiac Rehabilitation).

PMID- 20808159
TI  - Clinical use of immunosuppressants in Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a degenerative disease primarily affecting
      voluntary muscles with secondary consequences on heart and breathing muscles. DMD
      is an X-linked recessive disease that results in the loss of dystrophin, a key
      muscle protein. Inflammation can play different roles in DMD; it can be a
      secondary response to muscle degeneration, a primary cause of degeneration, or
      can contribute to the disease progression. Several immunosuppressants have been
      used with the aim to reduce the inflammation associated with DMD. Most recently,
      myoblast transplantation has shown the possibility to restore the dystrophin lack
      in the DMD patient's muscle fibers and this evidence has emphasized the
      importance of the use of immunosuppressants and the necessity of studying them
      and their secondary effects. The aim of this review is to analyze the main
      immunosuppressants drugs starting from the mdx mice experiments and concluding
      with the most recent human clinical studies.

PMID- 20808160
TI  - Neuromuscular pathology unknown.

PMID- 20808161
TI  - Isolated neck extensor myopathy: is it responsive to immunotherapy?
AB  - OBJECTIVE: To determine if isolated neck extensor myopathy (INEM) is responsive
      to immunosuppressive treatment. METHODS: We retrospectively reviewed charts of
      patients with INEM from 2002 to 2008 to identify patients and determine the
      response to immunomodulatory therapy. Clinical, electrodiagnostic, histologic,
      and radiographic data were reviewed. RESULTS: Four patients were identified
      during the study period. Three were women. The age of onset of neck extensor
      weakness ranged from 58 to 78 years. Serum creatine kinase levels were within
      normal limits in all patients. None had clinical, laboratory, or
      electrophysiological findings to suggest a generalized neuromuscular disorder. On
      electrodiagnostic studies, all patients had myopathic changes with or without
      irritative features in cervical paraspinal muscles. No inflammation was present
      on muscle biopsy from three of the patients. All patients received one or more
      immunosuppressive agents. Neck strength improved by 1 point or greater on the
      Medical Research Council scale in all subjects with a peak response observed
      between 3 and 6 months after treatment initiation. CONCLUSIONS: A trial of
      immunosuppressive agents should be offered to patients with INEM because a subset
      will improve. Rigorously defined, INEM is a noninflammatory myopathy. However, a
      focal myositis could be missed on muscle biopsy and may explain the favorable
      response to treatment.

PMID- 20808162
TI  - Adult-onset acid maltase deficiency with isolated axial muscle involvement.
AB  - INTRODUCTION: We report a patient with acid maltase deficiency who presented with
      subacute respiratory failure as the first symptom without significant extremity
      weakness. METHODS AND RESULTS: Electromyography of extremities was normal but
      showed myopathic changes and myotonic discharges limited to axial muscles only.
      Muscle biopsy confirmed the diagnosis. CONCLUSION: It is essential to examine
      axial muscles during electromyography if a patient presents with respiratory
      failure of unclear etiology even if the clinical examination does not show
      significant weakness in the extremities and electromyographic findings in the
      extremities are unremarkable.

PMID- 20808163
TI  - Paraneoplastic motor neuron disease associated with Purkinje cell autoantibody
      type 1.
AB  - Motor neuron disease has been reported as a rare result of systemic cancers,
      likely related to an autoimmune effecter mechanism. These patients have been
      described as having a more rapid onset of symptoms than typical motor neuron
      disease. Few of these reports demonstrate an association of a cancer-related
      autoantibody and with motor neuron disease. We present a 54-year-old woman with
      infiltrating ductal carcinoma of the breast who later developed lower motor
      neuron disease and was found to have Purkinje cell autoantibodies type 1. The
      association of lower motor neuron disease as a consequence of breast cancer with
      this autoantibody profile has not been described previously. This report
      emphasizes the importance of considering a paraneoplastic syndrome in a patient
      with an uncommon presentation of motor neuron disease.

PMID- 20808164
TI  - Chronic inflammatory demyelinating polyneuropathy and respiratory failure due to
      phrenic nerve involvement.
AB  - In this article, 2 patients with chronic inflammatory demyelinating
      polyneuropathy (CIDP) are presented. These patients developed respiratory failure
      which could not be explained by any cardiac or pulmonary pathology. The first
      case had pure motor involvement and probable CIDP, and the second case had severe
      sensorial dysfunction and an ataxic picture in addition to motor symptoms. His
      clinical picture was compatible with distal acquired demyelinating sensory
      neuropathy without M protein. Electrophysiologic investigations of both patients
      disclosed impaired phrenic nerve conduction and neurogenic motor unit changes in
      the diaphragm. Both patients showed a moderate response to immunotherapy. Distal
      acquired demyelinating sensory and pure motor variant of CIDP can be a cause of
      respiratory dysfunction. Different clinical patterns of CIDP should be evaluated
      for phrenic nerve involvement.

PMID- 20808166
TI  - Gout in the Hmong in the United States.
AB  - OBJECTIVE: To compare characteristics of gout in Hmong patients versus whites,
      and examine if Hmong ethnicity is associated with risk of tophaceous gout.
      METHODS: A retrospective chart review of Hmong and White patients with gout in a
      large health care system (Health Partners) in St. Paul, Minnesota, from January
      2001 to March 2008, to compare clinical characteristics and risk factors for
      gout. Multivariable-adjusted hierarchical logistic regressions examined the
      association of Hmong ethnicity with risk of tophaceous gout, adjusting for age,
      sex, hypertension, diuretic use, and kidney function. RESULTS: The analytic
      dataset consisted of 89 Hmong patients and 84 White controls, all of whom had
      ethnicity confirmed, an International Classification of Diseases, ninth revision
      code for gout and had at least 2 physician-documented diagnoses of gout. The
      Hmong group was younger (58.3 vs. 66.3 years, P = 0.04), had an earlier onset of
      symptoms (37.4 vs. 55.0 years, P < 0.001) and higher mean serum uric acid levels
      during follow-up (9.1 vs. 7.6 mg/dL, P < or = 0.001). Hmong had higher rates of
      tophaceous gout (31.5% vs. 10.7%, P = 0.001), including hand tophi (21.3% vs.
      3.6%, P < 0.001). In multivariable analyses that adjusted for age, sex,
      hypertension, diuretic, use, and kidney function, Hmong ethnicity was
      significantly associated with risk of tophaceous gout, with odds ratio 4.3 (95%
      confidence interval: 1.5, 12.2). CONCLUSION: Hmong patients have an earlier onset
      of gout symptoms. Hmong race is an independent risk factor for tophaceous gout.
      Future studies need to examine whether genetic or other comorbid factors predict
      this higher risk of more severe gout in Hmong.

PMID- 20808168
TI  - Evolving connective tissue disease influenced by splenectomy: beneath the sword
      of Dameshek.
AB  - In years past, there was concern that splenectomy could lead to dissemination of
      occult systemic lupus erythematosus. Clinical studies subsequently effectively
      refuted that concept. However, there remains uncertainty regarding the role of
      the spleen in autoimmune diseases and the effect of splenectomy on their course.
      We present a case of a 56-year-old woman with autoimmune hepatitis and rheumatoid
      arthritis, without clinical or serologic features of lupus, who developed
      glomerulonephritis and antiphospholipid syndrome subsequent to an elective
      splenectomy. Literature review was performed to identify examples of the effect
      of splenectomy on other autoimmune diseases. Splenectomy has been linked with the
      development of new autoimmune phenomenon, alterations in the clinical course of
      patients with prior autoimmune disease, such as in our patient, and in a
      progressive redistribution of memory B cells that may influence autoimmune
      disease activity and may have been involved in the alteration in our patient's
      clinical course.

PMID- 20808167
TI  - Tumor necrosis factor-alpha antagonist-induced sarcoidosis.
AB  - Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Tumor
      necrosis factor (TNF)-alpha is an important player in granuloma formation, and
      recent clinical trials have investigated the efficacy of TNF-alpha inhibitors in
      sarcoidosis. Paradoxically, there are several case reports in the medical
      literature describing the development of sarcoidosis in patients treated with TNF
      alpha inhibitors. We describe 3 cases of TNF-alpha antagonist-induced
      sarcoidosis: 1 case of pulmonary, ocular and cutaneous sarcoidosis developing in
      a patient receiving infliximab for erosive rheumatoid arthritis, 1 case of
      etanercept-induced sarcoidosis in a patient with seronegative rheumatoid
      arthritis, and 1 case of sarcoidosis developing in a patient receiving etanercept
      for erosive rheumatoid arthritis. We also provide a brief discussion on the role
      of TNF alpha in granuloma formation and implications in the use of TNF-alpha
      antagonists in autoimmune disease.

PMID- 20808169
TI  - Desquamative interstitial pneumonia as the initial manifestation of systemic
      sclerosis.
AB  - Interstitial lung disease (ILD) is a frequent pulmonary complication of systemic
      sclerosis (SSc), and nonspecific interstitial pneumonia is the most commonly
      recognized pattern of lung injury in these patients. In this report, we describe
      a never-smoker female presenting with Raynaud phenomenon and ILD that
      demonstrated desquamative interstitial pneumonia (DIP) on surgical lung biopsy.
      After 8 months, she was diagnosed with pulmonary hypertension at which time
      clinical examinations and serologic findings established the diagnosis of SSc.
      This case report expands the spectrum of patterns of ILD seen in association with
      SSc to include DIP.

PMID- 20808170
TI  - Nodular mucinosis in Graves disease mimicking gouty tophi.
AB  - We report a patient who had Graves disease and recently developed subcutaneous
      nodules over both lower limbs. Initially, gouty tophi were suspected by the
      endocrinologist so he was referred to the rheumatology clinic. However, a series
      of studies, including soft tissue ultrasonography, magnetic resonance image, and
      biopsy revealed nodular mucinosis resulting from Graves dermopathy. Nodular
      mucinosis is an unusual form of myxedema which mimics tophaceous gout, and should
      be considered in patients with Graves disease presenting with subcutaneous
      nodules.

PMID- 20808171
TI  - Familial Mediterranean fever presenting as anti-cyclic citrullinated peptide
      antibody negative palindromic rheumatism.
AB  - A 64-year-old Egyptian man who resides in the United States presented to the
      rheumatology clinic with 6 months history of episodic recurrent pauci--arthritis
      along with constitutional symptoms. His Mediterranean ancestry, anti-cyclic
      citrullinated peptide negativity, and cyclical palindromic rheumatism prompted an
      investigation for familial Mediterranean fever gene mutation. He was found to
      have heterozygous 694I gene mutation during MEFV analysis. He also met Liveneh 1
      major and 1 minor criteria for the diagnosis of familial Mediterranean fever.

PMID- 20808172
TI  - Tophaceous gout mimicking osteomyelitis: the value of musculoskeletal ultrasound
      in establishing the diagnosis.

PMID- 20808173
TI  - Pericardial tamponade as the initial presentation in a patient with polymyositis.

PMID- 20808174
TI  - Diffuse palpable tendon friction rubs in a patient with seronegative erosive
      polyarthritis.

PMID- 20808175
TI  - Chronic Budd-Chiari syndrome, abdominal varices, and caput medusae in 2 patients
      with antiphospholipid syndrome.

PMID- 20808176
TI  - End-stage hemophilic arthropathy in a patient from a developing nation.

PMID- 20808178
TI  - Gout as an early warning of concomitant sleep apnea.

PMID- 20808180
TI  - Monoclonal stool antigen testing for diagnosing Helicobacter pylori in young
      children: revisited.

PMID- 20808181
TI  - Genetic prothrombotic risk factors in children with extrahepatic portal vein
      obstruction.

PMID- 20808183
TI  - Calling all opinion leaders! Keys to the diffusion of evidence.

PMID- 20808182
TI  - Sex differences in how stress affects brain activity during face viewing.
AB  - Under stress, men tend to withdraw socially whereas women seek social support.
      This functional magnetic resonance imaging study indicates that stress also
      affects brain activity while viewing emotional faces differently for men and
      women. Fusiform face area response to faces was diminished by acute stress in men
      but increased by stress in women. Furthermore, among stressed men viewing angry
      faces, brain regions involved in interpreting and understanding others' emotions
      (the insula, temporal pole, and inferior frontal gyrus) showed reduced
      coordination with the fusiform face area and the amygdala, whereas the functional
      connectivity among these regions increased with stress for women. These findings
      suggest that stress influences emotional perception differently for men and
      women.

PMID- 20808184
TI  - Influencing outlook: The importance of nursing staff satisfaction.

PMID- 20808185
TI  - Clinical leaders and the adoption of health IT.

PMID- 20808187
TI  - Quality improvement What does it mean at the point-of-care?

PMID- 20808188
TI  - Staffing budgets: Planning, executing and managing into the future.

PMID- 20808189
TI  - The Magnet journey of a community hospital.

PMID- 20808190
TI  - How to prepare a successful grant proposal.

PMID- 20808191
TI  - CSI: Who are you?

PMID- 20808192
TI  - Confronting micromanaging bosses and nurse substance abuse.

PMID- 20808194
TI  - Silver yoga exercises improved physical fitness of transitional frail elders.
AB  - BACKGROUND: Promoting the health of transitional frail elders (e.g., through
      therapeutic-based yoga exercises) is essential to reduce healthcare expenditures
      caused by chronic health problems. OBJECTIVE: The purpose of this study was to
      determine the efficacy of 24 weeks of the senior-tailored silver yoga (SY)
      exercise program for transitional frail elders. METHODS: A convenience sample of
      69 elders in assisted living facilities were assigned randomly to the SY group (n
      = 38) or to the control group (n = 31) on the basis of the facilities where they
      resided, and 55 of them completed this quasi-experimental pretest and posttest
      study. Intervention was conducted three times per week, 70 minutes per session,
      for 24 weeks. Physical fitness (body composition, cardiovascular-respiratory
      functions, body flexibility, muscle power and endurance, balance, and agility)
      were examined at baseline, at 12 weeks, and at the end of the 24th week of the
      study. RESULTS: At the end of the study, the physical fitness indicators of
      participants in the SY group had improved significantly, and they had better
      physical fitness than participants in the control group (all p values < .05).
      DISCUSSION: It was recommended that the SY exercises be incorporated as an
      activity program in assisted living facilities to promote the physical fitness of
      transitional frail elders.

PMID- 20808193
TI  - The influence of literacy on patient-reported experiences of diabetes self
      management support.
AB  - BACKGROUND: Variability in disease-related outcomes may relate to how patients
      experience self-management support in clinical settings. OBJECTIVES: The purpose
      of this study was to identify factors associated with experiences of self
      management support during primary care encounters. METHODS: A cross-sectional
      survey was conducted of 208 patients seen in a multidisciplinary diabetes program
      in an academic medicine clinic. Multiple regression analysis was used to test
      associations between patient-rated experiences of self-management support
      (Patient Assessment of Chronic Illness Care) and race, gender, insurance status,
      literacy, duration of diabetes, and intensity of care management. RESULTS: The
      Patient Assessment of Chronic Illness Care ratings decreased with age (r = -.235,
      p = .001), were higher for women than for men (3.95 vs. 3.65, t = 2.612, p=
      .010), and were greater for those with more education (F= 3.927, p = .009) and
      greater literacy skills (t = 3.839, p< .001). The ratings did not vary between
      racial (t = -1.108, p = .269) or insurance (F = 1.045, p = .374) groups and were
      unaffected by the duration of diabetes (r= .052, p = .466) and the intensity of
      care management (F = 1.028, p = .360). In multivariate models, literacy was the
      only variable contributing significantly to variation in self-management support
      ratings. DISCUSSION: Even when considering the objective intensity of health
      services delivered, literacy was the sole variable contributing to differences in
      patient ratings of self-management support. Although conclusions are limited by
      the cross-sectional nature of this study, the results emphasize the need to
      consider literacy when developing and communicating treatment plans requiring
      self-management skills.

PMID- 20808199
TI  - Re: Chou R, Loeser JD,Owens DK, et al. Interventional therapies, surgery, and
      interdisciplinary rehabilitation for low back pain: an evidence-based clinical
      practice guideline from the American Pain Society. Spine 2009; 34:1066-77.

PMID- 20808200
TI  - Re: Cappuccino A, Bisson LJ, Carpenter B, et al. The use of systemic hypothermia
      for the treatment of an acute cervical spinal cord injury in a professional
      football player. Spine 2010;35:E57-62.

PMID- 20808202
TI  - Decreased sexual risk behavior in the era of HAART among HIV-infected urban and
      rural South Africans attending primary care clinics.
AB  - OBJECTIVE: In light of increasing access to HAART in sub-Saharan Africa, we
      conducted a longitudinal study to assess the impact of HAART on sexual risk
      behaviors among HIV-infected South Africans in urban and rural primary care
      clinics. DESIGN: Prospective observational cohort. METHODS: We conducted a cohort
      study at rural and urban primary care HIV clinics in South Africa consisting of
      1544 men and 4719 women enrolled from 2003 to 2010, representing 19703 clinic
      visits. The primary outcomes were being sexually active, unprotected sex, and
      more than one sex partner and were evaluated at 6 monthly intervals. Generalized
      estimated equations assessed the impact of HAART on sexual risk behaviors.
      RESULTS: Among 6263 HIV-infected men and women, over a third (37.2%) initiated
      HAART during study follow-up. In comparison to pre-HAART follow-up, visits while
      receiving HAART were associated with a decrease in those reporting being sexually
      active [adjusted odds ratio: 0.86 (95% confidence interval: 0.78-0.95)].
      Unprotected sex and having more than one sex partner were reduced at visits
      following HAART initiation compared to pre-HAART visits [adjusted odds ratio:
      0.40 (95% confidence interval: 0.34-0.46) and adjusted odds ratio: 0.20 (95%
      confidence interval: 0.14-0.29), respectively]. CONCLUSION: Sexual risk behavior
      significantly decreased following HAART initiation among HIV-infected South
      African men and women in primary care programs. The further expansion of
      antiretroviral treatment programs could enhance HIV prevention efforts in Africa.

PMID- 20808203
TI  - CXCR4-using viruses in plasma and peripheral blood mononuclear cells during
      primary HIV-1 infection and impact on disease progression.
AB  - OBJECTIVE: Cysteine-cysteine receptor 5 (CCR5)-using viruses classically
      predominate during HIV-1 primary infection but the frequency of cysteine-X
      cysteine receptor 4 (CXCR4)-using viruses varies between studies and could be
      different between plasma and peripheral blood mononuclear cells (PBMCs). Thus, we
      determined HIV-1 tropism in both these compartments during primary infection and
      evaluated the impact of CXCR4-using viruses on disease progression. DESIGN: One
      hundred and thirty-three patients with primary HIV-1 infection were screened for
      HIV-1 coreceptor usage in plasma and PBMCs using both genotypic and phenotypic
      methods. The impact of CXCR4-using viruses' transmission on subsequent disease
      progression was assessed in a case-control study. METHODS: HIV-1 coreceptor usage
      was determined using a recombinant virus phenotypic entry assay and V3-based
      genotypic algorithms. We also monitored CD4(+) T-cell count, clinical events and
      therapeutic intervention. RESULTS: There was 6.4% of CXCR4-using HIV-1 in plasma
      during primary infection as measured by a phenotypic assay and combined criteria
      from the 11/25 and net charge genotypic rules. Geno2pheno10 overestimated the
      prevalence of CXCR4-using viruses (12%). HIV-1 tropism in plasma and PBMCs was
      98% concordant. The HIV-1 RNA load and CD4(+) T-cell count during primary
      infection were not related to virus tropism. Primary infection with CXCR4-using
      viruses was associated with an accelerated rate of disease progression, estimated
      by a faster decline of CD4 T-cell count under 350 cells/microl and by a reduced
      delay in initiating a first antiretroviral treatment. CONCLUSIONS: Plasma or PBMC
      samples can be used for determining HIV-1 tropism during primary infection. CXCR4
      using viruses are rare during primary infection but increase the risk of disease
      progression.

PMID- 20808205
TI  - Sevoflurane and QTc Prolongation: An Interesting Observation, or a Clinically
      Significant Finding?

PMID- 20808204
TI  - Randomized placebo-controlled trial of prednisone for paradoxical tuberculosis
      associated immune reconstitution inflammatory syndrome.
AB  - OBJECTIVE: Paradoxical tuberculosis-associated immune reconstitution inflammatory
      syndrome (TB-IRIS) is a frequent complication of antiretroviral therapy in
      resource-limited countries. We aimed to assess whether a 4-week course of
      prednisone would reduce morbidity in patients with paradoxical TB-IRIS without
      excess adverse events. DESIGN: A randomized, double-blind, placebo-controlled
      trial of prednisone (1.5 mg/kg per day for 2 weeks then 0.75 mg/kg per day for 2
      weeks). Patients with immediately life-threatening TB-IRIS manifestations were
      excluded. METHODS: The primary combined endpoint was days of hospitalization and
      outpatient therapeutic procedures, which were counted as one hospital day.
      RESULTS: One hundred and ten participants were enrolled (55 to each arm). The
      primary combined endpoint was more frequent in the placebo than the prednisone
      arm {median hospital days 3 [interquartile range (IQR) 0-9] and 0 (IQR 0-3),
      respectively; P = 0.04}. There were significantly greater improvements in
      symptoms, Karnofsky score, and quality of life (MOS-HIV) in the prednisone vs.
      the placebo arm at 2 and 4 weeks, but not at later time points. Chest radiographs
      improved significantly more in the prednisone arm at weeks 2 (P = 0.002) and 4 (P
      = 0.02). Infections on study medication occurred in more participants in
      prednisone than in placebo arm (27 vs. 17, respectively; P = 0.05), but there was
      no difference in severe infections (2 vs. 4, respectively; P = 0.40). Isolates
      from 10 participants were found to be resistant to rifampicin after enrolment.
      CONCLUSION: Prednisone reduced the need for hospitalization and therapeutic
      procedures and hastened improvements in symptoms, performance, and quality of
      life. It is important to investigate for drug-resistant tuberculosis and other
      causes for deterioration before administering glucocorticoids.

PMID- 20808206
TI  - Modeling the effect of sevoflurane on corrected QT prolongation: a
      pharmacodynamic analysis.
AB  - BACKGROUND: Sevoflurane may prolong the corrected QT (QTc) interval in healthy
      humans when administered for induction and maintenance of anesthesia. Little
      information is available about the dose-response relationship of sevoflurane on
      the QTc interval. We performed a pharmacodynamic analysis of the relationship
      between end-tidal sevoflurane concentration (CET) and the QTc. METHODS: Twenty
      one patients aged 20-50 yr were enrolled in this study. Sevoflurane
      concentrations were progressively increased and then decreased over 15 min at the
      start of anesthesia; CET and automated QT interval were recorded continuously.
      Pharmacodynamic analysis using a sigmoid Emax model was performed to assess the
      concentration-effect relationship. RESULTS: Maximal CET was 4.30 +/- 0.33%.
      Measured baseline and maximally prolonged QTc interval values were 351.7 +/- 15.4
      ms and 397.8 +/- 17.5 ms, respectively. During sevoflurane anesthesia, increased
      concentrations were correlated with prolonged QTc interval. Hysteresis between
      the CET and QTc interval were observed and accounted for in the model. Ce50 and
      ke0 were 2.5 +/- 1.4 and 2.0 +/- 1.0, respectively. The median prediction error,
      median absolute prediction error, and the coefficient of determination (R) were
      0.02%, 0.75%, and 0.95, respectively. The effect-site concentration (Ce50) and
      QTc interval data fit to a sigmoid Emax model. CONCLUSIONS: Among patients
      receiving sevoflurane for anesthesia, QTc interval changes correlate to
      anesthetic level. The Ce50 for significant QTc change is at clinically relevant
      levels of sevoflurane anesthesia.

PMID- 20808207
TI  - Perioperative outcomes among patients with the modified metabolic syndrome who
      are undergoing noncardiac surgery.
AB  - BACKGROUND: Previous studies have demonstrated that obesity is paradoxically
      associated with a lower risk of mortality after noncardiac surgery. This study
      will determine the impact of the modified metabolic syndrome (defined as the
      presence of obesity, hypertension, and diabetes) on perioperative outcomes.
      METHODS: This study is based on data from 310,208 patients in the American
      College of Surgeons National Surgical Quality Improvement Program database. We
      estimated separate multivariate logistic regression models for 30-day mortality
      and for 30-day complications. RESULTS: Patients with the modified metabolic
      syndrome who are super obese had a 2-fold increased risk of death (adjusted odds
      ratio [AOR] 1.99; 95% CI 1.41-2.80). As stratified by body mass index, patients
      with the modified metabolic syndrome had a 2- to 2.5-fold higher risk of cardiac
      adverse events (CAE) compared with normal-weight patients: obese (AOR 1.70; 95%
      CI 1.40-2.07), morbidly obese (AOR 2.01; 95% CI 1.48-2.73), and super obese (AOR
      2.66; 95% CI 1.68-4.19). In addition, the risk of acute kidney injury (AKI) was 3
      to 7-fold higher in these patients: obese (AOR 3.30; 95% CI 2.75-3.94), morbidly
      obese (AOR 5.01; 95% CI 3.87-6.49), and super obese (AOR 7.29; 95% CI 5.27-10.1).
      CONCLUSION: Patients with the modified metabolic syndrome undergoing noncardiac
      surgery are at substantially higher risk of complications compared with patients
      of normal weight.

PMID- 20808208
TI  - Prediction of pediatric endotracheal tube size by ultrasonography.
AB  - BACKGROUND: Formulas based on age and height often fail to reliably predict the
      proper endotracheal tube (ETT) size in pediatric patients. We, thus, tested the
      hypothesis that subglottic diameter, as determined by ultrasonography, better
      predicts optimal ETT size than existing methods. METHODS: A total of 192
      patients, aged 1 month to 6 yr, who were scheduled for surgery and undergoing
      general anesthesia were enrolled and divided into development and validation
      phases. In the development group, the optimal ETT size was selected according to
      standard age-based formulas for cuffed and uncuffed tubes. Tubes were replaced as
      necessary until a good clinical fit was obtained. Via ultrasonography, the
      subglottic upper airway diameter was determined before tracheal intubation. We
      constructed a regression equation between the subglottic upper airway diameter
      and the outer diameter of the ETT finally selected. In the validation group, ETT
      size was selected after ultrasonography using this regression equation. The
      primary outcome was the fraction of initial cuffed and uncuffed tube sizes, as
      selected through the regression formula, that proved clinically optimal. RESULTS:
      Subglottic upper airway diameter was highly correlated with outer ETT diameter
      deemed optimal on clinical grounds. The rate of agreement between the predicted
      ETT size based on ultrasonic measurement and the final ETT size selected
      clinically was 98% for cuffed ETTs and 96% for uncuffed ETTs. CONCLUSIONS:
      Measuring subglottic airway diameter with ultrasonography facilitates the
      selection of appropriately sized ETTs in pediatric patients. This selection
      method better predicted optimal outer ETT diameter than standard age- and height
      based formulas.

PMID- 20808209
TI  - Pros and cons of composite endpoints in anesthesia trials.

PMID- 20808210
TI  - A two-handed jaw-thrust technique is superior to the one-handed "EC-clamp"
      technique for mask ventilation in the apneic unconscious person.
AB  - BACKGROUND: Mask ventilation is considered a "basic" skill for airway management.
      A one-handed "EC-clamp" technique is most often used after induction of
      anesthesia with a two-handed jaw-thrust technique reserved for difficult cases.
      Our aim was to directly compare both techniques with the primary outcome of air
      exchange in the lungs. METHODS: Forty-two elective surgical patients were mask
      ventilated after induction of anesthesia by using a one-handed "EC-clamp"
      technique and a two-handed jaw-thrust technique during pressure-control
      ventilation in randomized, crossover fashion. When unresponsive to a jaw thrust,
      expired tidal volumes were recorded from the expiratory limb of the anesthesia
      machine each for five consecutive breaths. Inadequate mask ventilation and dead
      space ventilation were defined as an average tidal volume less than 4 ml/kg
      predicted body weight or less than 150 ml/breath, respectively. Differences in
      minute ventilation and tidal volume between techniques were assessed with the use
      of a mixed-effects model. RESULTS: Patients were (mean +/- SD) 56 +/- 18 yr old
      with a body mass index of 30 +/- 7.1 kg/m. Minute ventilation was 6.32 +/- 3.24
      l/min with one hand and 7.95 +/- 2.70 l/min with two hands. The tidal volume was
      6.80 +/- 3.10 ml/kg predicted body weight with one hand and 8.60 +/- 2.31 ml/kg
      predicted body weight with two hands. Improvement with two hands was independent
      of the order used. Inadequate or dead-space ventilation occurred more frequently
      during use of the one-handed compared with the two-handed technique (14 vs. 5%; P
      = 0.013). CONCLUSION: A two-handed jaw-thrust mask technique improves upper
      airway patency as measured by greater tidal volumes during pressure-controlled
      ventilation than a one-handed "EC-clamp" technique in the unconscious apneic
      person.

PMID- 20808211
TI  - Equivalence and noninferiority testing in anesthesiology research.

PMID- 20808212
TI  - A mouse model of ischemic spinal cord injury with delayed paralysis caused by
      aortic cross-clamping.
AB  - BACKGROUND: Spinal cord ischemia and paralysis are devastating perioperative
      complications that can accompany open or endovascular repair surgery for aortic
      aneurysms. Here, we report on the development of a new mouse model of spinal cord
      ischemia with delayed paralysis induced by cross-clamping the descending aorta.
      METHODS: Transient aortic occlusion was produced in mice by cross-clamping the
      descending aorta through a lateral thoracotomy. To establish an optimal surgical
      procedure with limited mortality, variable cross-clamp times and core
      temperatures were tested between experiments. RESULTS: The onset of paresis or
      paralysis and postsurgical mortality varied as a function of cross-clamp time and
      core temperature that was maintained during the period of cross-clamp. Using
      optimal surgical parameters (7.5-min cross-clamp duration at 33 degrees C core
      temperature), the onset of paralysis is delayed 24-36 h after reperfusion, and
      more than 95% of mice survive through 9 weeks after surgery. These mice are
      further stratified into two groups, 70% (n = 19/27) of mice developing severe
      hind limb paralysis and the remaining mice showing mild, though still permanent,
      behavioral deficits. CONCLUSION: This new model should prove useful as a
      preclinical tool for screening neuroprotective therapeutics and for defining the
      basic biologic mechanisms that cause delayed paralysis and neurodegeneration
      after transient spinal cord ischemia.

PMID- 20808213
TI  - Propofol modulates agonist-induced transient receptor potential vanilloid subtype
      1 receptor desensitization via a protein kinase Cepsilon-dependent pathway in
      mouse dorsal root ganglion sensory neurons.
AB  - BACKGROUND: The activity of transient receptor potential vanilloid subtype-1
      (TRPV1) receptors, key nociceptive transducers in dorsal root ganglion sensory
      neurons, is enhanced by protein kinase C epsilon (PKCepsilon) activation. The
      intravenous anesthetic propofol has been shown to activate PKCepsilon. Our
      objectives were to examine whether propofol modulates TRPV1 function in dorsal
      root ganglion neurons via activation of PKCepsilon. METHODS: Lumbar dorsal root
      ganglion neurons from wild-type and PKC& epsilon;-null mice were isolated and
      cultured for 24 h. Intracellular free Ca concentration was measured in neurons by
      using fura-2 acetoxymethyl ester. The duration of pain-associated behaviors was
      also assessed. Phosphorylation of PKCepsilon and TRPV1 and the cellular
      translocation of PKCepsilon from cytosol to membrane compartments were assessed
      by immunoblot analysis. RESULTS: In wild-type neurons, repeated stimulation with
      capsaicin (100 nm) progressively decreased the transient rise in intracellular
      free Ca concentration. After desensitization, exposure to propofol rescued the Ca
      response. The resensitizing effect of propofol was absent in neurons obtained
      from PKCepsilon-null mice. Moreover, the capsaicin-induced desensitization of
      TRPV1 was markedly attenuated in the presence of propofol in neurons from wild
      type mice but not in neurons from PKCepsilon-null mice. Propofol also prolonged
      the duration of agonist-induced pain associated behaviors in wild-type mice. In
      addition, propofol increased phosphorylation of PKCepsilon as well as TRPV1 and
      stimulated translocation of PKCepsilon from cytosolic to membrane fraction.
      DISCUSSION: Our results indicate that propofol modulates TRPV1 sensitivity to
      capsaicin and that this most likely occurs through a PKCepsilon-mediated
      phosphorylation of TRPV1.

PMID- 20808214
TI  - To beat or not to beat: is timing the only question? Survival after delayed
      defibrillation.

PMID- 20808215
TI  - Delayed time to defibrillation after intraoperative and periprocedural cardiac
      arrest.
AB  - BACKGROUND: Delay in defibrillation (more than 2 min) is associated with worse
      survival in patients with a cardiac arrest because of ventricular fibrillation or
      pulseless ventricular tachycardia in intensive care units and inpatient wards.
      METHODS: We tested the relationship between delayed defibrillation and survival
      from intraoperative or periprocedural cardiac arrest, adjusting for baseline
      patient characteristics. The analysis was based on data from 865 patients who had
      intraoperative or periprocedural cardiac arrest caused by ventricular
      fibrillation or pulseless ventricular tachycardia in 259 hospitals participating
      in the National Registry of Cardiopulmonary Resuscitation. RESULTS: The median
      time to defibrillation was less than 1 min (interquartile range, <1 to 1 min).
      Delays in defibrillation occurred in 119 patients (13.8%). Characteristics
      associated with delayed defibrillation included pulseless ventricular tachycardia
      and noncardiac admitting diagnosis. The association between delayed
      defibrillation and survival to hospital discharge differed for periprocedural and
      intraoperative cardiac arrests (P value for interaction = 0.003). For patients
      arresting outside the operating room, delayed defibrillation was associated with
      a lower probability of surviving to hospital discharge (31.6% vs. 62.1%, adjusted
      odds ratio 0.49; 95% CI 0.27, 0.88; P = 0.018). In contrast, delayed
      defibrillation was not associated with survival for cardiac arrests in the
      operating room (46.8% vs. 39.6%, adjusted odds ratio 1.23, 95% CI 0.70, 2.19, P =
      0.47). CONCLUSIONS: Delays in defibrillation occurred in one of seven cardiac
      arrests in the intraoperative and periprocedural arenas. Although delayed
      defibrillation was associated with lower rates of survival after cardiac arrests
      in periprocedural areas, there was no association with survival for cardiac
      arrests in the operating room.

PMID- 20808216
TI  - Relationship between normalized adductor pollicis train-of-four ratio and
      manifestations of residual neuromuscular block: a study using acceleromyography
      during near steady-state concentrations of mivacurium.
AB  - BACKGROUND: Baseline acceleromyographic adductor pollicis train-of-four (TOF)
      ratio varies significantly between individuals and is often greater than unity.
      Thus, normalization of acceleromyography data is necessary. The relationship
      between normalized acceleromyographic TOF ratio, lung volumes, and clinical signs
      of residual neuromuscular block was studied. METHODS: In 12 healthy volunteers,
      three steady-state levels of neuromuscular block were achieved with mivacurium
      infusions. TOF ratio was measured acceleromyographically at the adductor pollicis
      using a preload. Lung volume measurements and a series of clinical tests were
      made at each stable block and reconciled to the normalized TOF measures. RESULTS:
      None experienced airway obstruction or arterial oxygen desaturation, even at
      normalized TOF ratio less than 0.4. Functional residual capacity remained
      unchanged whereas vital capacity decreased linearly with decreasing TOF ratio.
      The ability to protrude the tongue was preserved at all times. The ability to
      clench the teeth was lost in one volunteer at normalized TOF ratio of 0.84 but
      retained in four at normalized TOF ratio less than 0.4. Four volunteers lost the
      ability both to raise the head more than 5 s and to swallow, with the most
      sensitive individual demonstrating these effects at normalized TOF ratio of 0.60.
      At mean normalized TOF ratio of 0.42, the mean handgrip strength was
      approximately 20% of baseline value. CONCLUSION: Lung vital capacity decreased
      linearly with decreasing TOF ratio. Responses to clinical tests of muscle
      function varied to a large extent among individuals at comparable TOF ratios.
      None of the volunteers had significant clinical effects of neuromuscular block at
      normalized acceleromyographic TOF ratio greater than 0.90.

PMID- 20808218
TI  - Second report of slipped capital femoral epiphysis in Rubinstein-Taybi syndrome.

PMID- 20808219
TI  - Learning through observation: the role of ethnography in improving critical care.
AB  - PURPOSE OF REVIEW: To determine the conditions under which ethnographic research
      is a useful tool for reflexive self-learning and enhanced performance in critical
      care units. RECENT FINDINGS: The focus of studies using qualitative methods to
      investigate the organization of work in critical care units largely remains the
      investigation of the stresses and strains for staff, patients, and families
      managing communication at the end of life. A more recent focus of research has
      been on safety and quality improvement. Iterative feedback between researchers
      and clinicians is likely a useful tool for self-reflexive learning and change.
      SUMMARY: Qualitative researchers have long been involved in the study of critical
      care. There is a new emphasis on using ethnographic methods as a tool for
      behavioural change through the process of iterative feedback.

PMID- 20808217
TI  - Acute anemia elicits cognitive dysfunction and evidence of cerebral cellular
      hypoxia in older rats with systemic hypertension.
AB  - BACKGROUND: Postoperative cognitive dysfunction occurs frequently after cardiac,
      major vascular, and major orthopedic surgery. Aging and hypertensive
      cerebrovascular disease are leading risk factors for this disorder. Acute anemia,
      common to major surgery, has been identified as a possible contributor to
      postoperative cognitive dysfunction. The effect of hypoxia upon cognition and the
      cellular and molecular processes involved in learning and memory has been well
      described. Cerebrovascular changes related to chronic hypertension may expose
      cells to increased hypoxia with anemia. METHODS: Young to aged spontaneously
      hypertensive rats underwent testing for visuospatial memory and learning in the
      Morris water maze, measurement of cerebral tissue oxygenation via tissue oxygen
      probe, and measurement of hypoxia-sensitive genes and proteins, under conditions
      of sham and experimental isovolemic anemia. RESULTS: Acute isovolemic anemia
      elicited evidence of aging-dependent visuospatial working memory and learning
      impairment. Isovolemic anemia did not result in cerebral tissue hypoxia, when
      measured via tissue oxygen probe. Evidence of cellular hypoxia was, however,
      identified in response to the anemic challenge, as hypoxia-sensitive genes and
      proteins were up-regulated. Importantly, cellular hypoxic gene responses were
      increased with anemia in an age-dependent manner in this model of aging with
      chronic hypertension. CONCLUSIONS: In a translational model of chronic
      hypertension, clinically relevant levels of acute anemia were associated with an
      age-dependent visuospatial working memory and learning impairment that was
      matched by an age-dependent cellular sensitivity to anemic hypoxia. These data
      offer support for a possible link between anemic hypoxia and postoperative
      cognitive dysfunction in humans.

PMID- 20808220
TI  - Blunt cerebrovascular trauma.
AB  - PURPOSE OF REVIEW: Blunt cerebrovascular injuries (BCVI) are a rare but
      potentially devastating injury with stroke rates up to 50%. Over the past decade,
      the recognition and subsequent management of these injuries has undergone a
      marked evolution. This review will focus on the rationale for BCVI screening,
      imaging options, and treatment modalities. RECENT FINDINGS: There are no
      prospective randomized controlled trials evaluating the management of BCVI.
      Available studies support screening a high-risk patient population based upon
      injury mechanism and constellation of associated injuries using multidetector-row
      (16-slice or greater) computed tomographic angiography (CTA). Although the ideal
      regimen of antithrombotic therapy has yet to be determined, treatment with either
      anticoagulation or antiplatelet agents has been shown to reduce BCVI-related
      stroke rate. SUMMARY: Cerebrovascular injuries (CVI) are now diagnosed in
      approximately 1% of blunt trauma patients. The recognition of a clinically silent
      period allows for injury screening based upon mechanism of trauma and the
      patient's injury pattern. Following identification of injuries in asymptomatic
      patients, prompt initiation of antithrombotic therapy reduces the incidence of
      stroke.

PMID- 20808222
TI  - Round window perfusion dynamics: implications for intracochlear therapy.
AB  - PURPOSE OF REVIEW: The treatments for inner ear diseases are evolving as the
      systemic administration of medication is replaced by novel intratympanic and
      intracochlear drug delivery. The current review explores the background and
      recent developments in this field. RECENT FINDINGS: Although still in various
      stages of clinical development, novel drug delivery techniques such as the
      Silverstein MicroWick, the round window microcatheter, biodegradable hydrogels,
      biopolymers, nanoparticles, newly designed cochlear implant arrays, osmotic
      mini/micro pumps, and reciprocating perfusion systems hold significant promise.
      Animal data suggest that sustained delivery systems have more reliable inner ear
      pharmacokinetics than both systemic administration and intratympanic injections.
      SUMMARY: As research scientists advance technologies for treating inner ear
      diseases, drug delivery techniques must keep pace. Viable treatment options for
      sensorineural hearing loss, tinnitus, and vestibular disorders are on the horizon
      and may usher in a new golden age for otology.

PMID- 20808221
TI  - Universal newborn hearing screening in 2010.
AB  - PURPOSE OF REVIEW: The objectives of this review are to provide the reader with a
      current and concise review of the data and trends in universal newborn hearing
      screening. Within a relatively short period of time, the concept of screening all
      infants for hearing loss at the time of birth has evolved from a nascent process
      to a truly universal system in most developed countries. As a result, the focus
      and challenges of universal newborn hearing screening have shifted to topics of
      developing even more efficient and cost-effective approaches, and potentially
      melding physiologic hearing screenings with ancillary screening techniques.
      RECENT FINDINGS: Enhancement of the universal newborn hearing screening process
      is likely to be accomplished by implementation of novel tools such as wideband
      reflectance technologies and intelligent incorporation of screening for common
      genetic and viral causes of congenital hearing loss. SUMMARY: With such a rapidly
      evolving process, it will be critical for clinicians to understand the benefits
      and limitations of various newborn hearing screening methodologies in order to
      determine the most appropriate management of children referred from their
      universal newborn hearing screening. This will entail a working knowledge of
      emerging audiologic tools as well as infectious and genetic causes of pediatric
      hearing loss.

PMID- 20808223
TI  - Hormonal approaches to male contraception.
AB  - PURPOSE OF REVIEW: Condoms and vasectomy are male-controlled family planning
      methods but suffer from limitations in compliance (condoms) and limited
      reversibility (vasectomy); thus many couples desire other options. Hormonal male
      contraceptive methods have undergone extensive clinical trials in healthy men and
      shown to be efficacious, reversible and appear to be well tolerated. RECENT
      FINDINGS: The success rate of male hormonal contraception using injectable
      testosterone alone is high and comparable to methods for women. Addition of
      progestins to androgens improved the rate of suppression of spermatogenesis.
      Supported by government or nongovernment organizations, current studies aim to
      find the best combination of testosterone and progestins for effective
      spermatogenesis suppression and to explore other delivery methods for these
      hormones. Translation of these advances to widespread use in the developed world
      will need the manufacturing and marketing skills of the pharmaceutical industry.
      Availability of male contraceptives to the developing world may require
      commitments of governmental and nongovernmental agencies. In a time when
      imbalance of basic resources and population needs are obvious, this may prove to
      be a very wise investment. SUMMARY: Male hormonal contraception is efficacious,
      reversible and well tolerated for the target population of younger men in stable
      relationships. Suppression of spermatogenesis is achieved with a combination of
      an androgen and a progestin. Partnership with industry will accelerate the
      marketing of a male hormonal contraceptive. Research is ongoing on selective
      androgen and progesterone receptor modulators that suppress spermatogenesis,
      minimize potential adverse events while retaining the androgenic and gonadotropin
      suppressive actions.

PMID- 20808224
TI  - Hypospadias surgery past, present and future.
AB  - PURPOSE OF REVIEW: Hypospadias surgery has been in continuous evolution for many
      years with steadily improving reported results. Despite this many unanswered
      questions on its cause, management and outcomes remain. Recent research has done
      little to clarify most matters. RECENT FINDINGS: There is increasing evidence of
      a balance of genetic and developmental factors in the development of hypospadias,
      but there is doubt whether the incidence of hypospadias is increasing or not.
      Many technical aspects of hypospadias repair and variations of perioperative
      management seem to have little effect on outcome, whereas the age at which
      surgery is performed may. Although efforts are being made to relate anatomical
      findings to outcome, a lack of objective assessment and standardization is a
      handicap. Severe hypospadias, particularly that associated with significant
      chordee, remains challenging although strategies for management are being
      developed. The future may lie in development of autologous tissue culture for
      these severe cases. SUMMARY: Further development of hypospadias surgery would
      benefit from objective, standardized methods of describing anatomy and outcome
      measures to facilitate effective comparison of techniques and procedures.

PMID- 20808225
TI  - Comparison of wireless and acoustic hearing aid-based telephone listening
      strategies.
AB  - OBJECTIVE: The purpose of this study was to examine speech recognition through
      hearing aids for seven telephone listening conditions. DESIGN: Speech recognition
      scores were measured for 20 participants in six wireless routing transmission
      conditions and one acoustic telephone condition. In the wireless conditions, the
      speech signal was delivered to both ears simultaneously (bilateral speech) or to
      one ear (unilateral speech). The effect of changing the noise level in the
      nontest ear during unilateral conditions was also examined. Participants were
      fitted with hearing aids using both nonoccluding and occluding dome ear tips.
      Participants were seated in a room with background noise present and speech was
      transmitted to the participants without additional noise. RESULTS: There was no
      effect of changing the noise level in the nontest ear and no difference between
      unilateral wireless routing and acoustic telephone listening. For wireless
      transmission, bilateral presentation resulted in significantly better speech
      recognition than unilateral presentation. Bilateral wireless conditions allowed
      for significantly better recognition than the acoustic telephone condition for
      participants fitted with occluding ear tips only. CONCLUSION: Routing the signal
      to both hearing aids resulted in significantly better speech recognition than
      unilateral signal routing. Wireless signal routing was shown to be beneficial
      compared with acoustic telephone listening and in some conditions resulted in the
      best performance of all of the listening conditions evaluated. However, this
      advantage was only evident when the signal was routed to both ears and when
      hearing aid wearers were fitted with occluding domes. Therefore, it is expected
      that the benefits of this new wireless streaming technology over existing
      telephone coupling methods will be most evident clinically in hearing aid wearers
      who require more limited venting than is typically used in open canal fittings.

PMID- 20808226
TI  - Sensitivity of the human binaural cortical steady state response to interaural
      level differences.
AB  - OBJECTIVES: Periodic alternations of the interaural correlation of a noise
      stimulus evoke an auditory steady state response that can be measured at the
      scalp, providing an objective measure of binaural integration. The purpose of
      this study was to examine the effect of interaural level differences on this
      steady state response. DESIGN: Auditory steady state responses at 4 and 8 Hz were
      recorded to 4 Hz cycles of interaural correlation change of a Gaussian noise in
      normal-hearing listeners. Responses were recorded with symmetric presentation
      levels of 80, 60, and 40 dB SPL and with interaural asymmetries ranging from 10
      to 40 dB, varying in 10-dB steps. RESULTS: The 8 Hz response was sensitive to
      interaural level asymmetry and fell to 50% strength at an asymmetry of 18 dB,
      although the response was detectable to an asymmetry of 30 dB. A simultaneously
      present 4 Hz response showed no sensitivity to interaural level difference.
      Significant responses were recorded in all participants. CONCLUSIONS: The 8 Hz
      auditory steady state response to a 4 Hz change in noise interaural correlation
      might be useful as an objective measure of binaural integration in asymmetric
      hearing loss. Response amplitude is more negatively affected by small amounts of
      interaural asymmetry than by large reductions in overall presentation level.

PMID- 20808227
TI  - A novel approach to increase awareness about hereditary colon cancer using a
      state cancer registry.
AB  - PURPOSE: The aim of this project was to conduct educational outreach about
      hereditary colon cancer to a targeted high risk population identified through a
      state cancer registry. METHODS: Individuals who met one of the first three
      Bethesda criteria guidelines were identified through the Colorado Central Cancer
      Registry. The physician of record received a brochure, survey and form to provide
      written consent to contact patient(s). Cases were mailed an educational brochure,
      initial and follow-up survey. RESULTS: Five hundred seventy-five cases and 412
      physicians were identified; 81% provided consent. Ninety percent of physicians
      felt the registry should provide this information to at-risk patients. Twenty
      three percent of the cases returned the survey. Cases were generally glad to get
      the information. Only four cases reported concern. The majority agreed the cancer
      registry should send the information, however most preferred their physicians be
      consented first. At follow-up, 20 cases reported having or intending to have a
      risk assessment. CONCLUSIONS: Response from physicians and cases was positive,
      suggesting that targeted outreach using cancer registries, in combination with
      physician notification, may be a viable approach to educational outreach about
      cancer genetics. A proportion of cases sought risk assessment, suggesting that
      mail-based outreach may be effective in increasing uptake of information and/or
      genetic services.

PMID- 20808228
TI  - Copy number variations associated with autism spectrum disorders contribute to a
      spectrum of neurodevelopmental disorders.
AB  - PURPOSE: Autism spectrum disorders represent a range of neurodevelopmental
      disorders that have been shown to have a strong genetic etiological component.
      Microarray-based comparative genomic hybridization and other molecular
      cytogenetic techniques are discovering an increasing number of copy number
      variations in individuals with autism spectrum disorder. METHODS: We examined the
      yield of abnormal microarray-based comparative genomic hybridization findings in
      our laboratory for individuals referred for testing for autism spectrum disorder.
      We also examined the presence of autistic features among 151 additional
      individuals who were referred for microarray-based comparative genomic
      hybridization testing for indications other than autism spectrum disorder but had
      genomic alterations overlapping those found in cases referred for autism spectrum
      disorder. RESULTS: We identified 1461 individuals referred for testing for autism
      spectrum disorder, with likely significant abnormalities reported in
      approximately 11.6% of individuals analyzed with whole-genome arrays. These
      abnormalities include alterations that encompass novel candidate genes such as
      SNTG2, SOX5, HFE, and TRIP38. A minority of individuals with overlapping
      abnormalities (19%) had autistic features, and many of the copy number variations
      identified in our study are inherited (69% among those found in individuals with
      autism spectrum disorder). CONCLUSIONS: Our results suggest these copy number
      variations are one of multiple factors contributing to the development of an
      autism spectrum disorder phenotype. Additionally, the broad phenotypic spectrum
      of the patients with these copy number variations suggests that these copy number
      variations are not autism spectrum disorder-specific but likely more generally
      impair neurodevelopment.

PMID- 20808229
TI  - A formal risk-benefit framework for genomic tests: facilitating the appropriate
      translation of genomics into clinical practice.
AB  - PURPOSE: Evaluation of genomic tests is often challenging because of the lack of
      direct evidence of clinical benefit compared with usual care and unclear evidence
      requirements. To address these issues, this study presents a risk-benefit
      framework for assessing the health-related utility of genomic tests. METHODS: We
      incorporated approaches from a variety of established fields including decision
      science, outcomes research, and health technology assessment to develop the
      framework. Additionally, we considered genomic test stakeholder perspectives and
      case studies. RESULTS: We developed a three-tiered framework: first, we use
      decision-analytic modeling techniques to synthesize data, project incidence of
      clinical events, and assess uncertainty. Second, we defined the health-related
      utility of genomic tests as improvement in health outcomes as measured by
      clinical event rates, life expectancy, and quality-adjusted life-years. Finally,
      we displayed results using a risk-benefit policy matrix to facilitate the
      interpretation and implementation of findings from these analyses. CONCLUSION: A
      formal risk-benefit framework may accelerate the utilization and practice-based
      evidence development of genomic tests that pose low risk and offer plausible
      clinical benefit, while discouraging premature use of tests that provide little
      benefit or pose significant health risks compared with usual care.

PMID- 20808230
TI  - Carrier testing for spinal muscular atrophy.
AB  - Spinal muscular atrophy is the most common fatal hereditary disease among
      newborns and infants. There is as yet no effective treatment. Although a carrier
      test is available, currently there is disagreement among professional medical
      societies who proffer standards of care as to whether or not carrier screening
      for spinal muscular atrophy should be offered as part of routine reproductive
      care. This leaves health care providers without clear guidance. In fall 2009, a
      meeting was held by National Institutes of Health to examine the scientific basis
      for spinal muscular atrophy carrier screening and to consider the issues that
      accompany such screening. In this article, the meeting participants summarize the
      discussions and conclude that pan-ethnic carrier screening for spinal muscular
      atrophy is technically feasible and that the specific study of implementing a
      spinal muscular atrophy carrier screening program raises broader issues about
      determining the scope and specifics of carrier screening in general.

PMID- 20808231
TI  - Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated
      with developmental delay and obesity.
AB  - PURPOSE: The short arm of chromosome 16 is rich in segmental duplications,
      predisposing this region of the genome to a number of recurrent rearrangements.
      Genomic imbalances of an approximately 600-kb region in 16p11.2 (29.5-30.1 Mb)
      have been associated with autism, intellectual disability, congenital anomalies,
      and schizophrenia. However, a separate, distal 200-kb region in 16p11.2 (28.7
      28.9 Mb) that includes the SH2B1 gene has been recently associated with isolated
      obesity. The purpose of this study was to better define the phenotype of this
      recurrent SH2B1-containing microdeletion in a cohort of phenotypically abnormal
      patients not selected for obesity. METHODS: Array comparative hybridization was
      performed on a total of 23,084 patients in a clinical setting for a variety of
      indications, most commonly developmental delay. RESULTS: Deletions of the SH2B1
      containing region were identified in 31 patients. The deletion is enriched in the
      patient population when compared with controls (P = 0.003), with both inherited
      and de novo events. Detailed clinical information was available for six patients,
      who all had developmental delays of varying severity. Body mass index was >=95th
      percentile in four of six patients, supporting the previously described
      association with obesity. The reciprocal duplication, found in 17 patients, does
      not seem to be significantly enriched in our patient population compared with
      controls. CONCLUSIONS: Deletions of the 16p11.2 SH2B1-containing region are
      pathogenic and are associated with developmental delay in addition to obesity.

PMID- 20808232
TI  - Quantitative volumetric perfusion mapping of the microvasculature using contrast
      ultrasound.
AB  - OBJECTIVES: Contrast-enhanced ultrasound imaging has demonstrated significant
      potential as a noninvasive technology for monitoring blood flow in the
      microvasculature. With the application of nondestructive contrast imaging pulse
      sequences combined with a clearance-refill approach, it is possible to create
      quantitative time-to-refill maps of tissue correlating to blood perfusion rate.
      One limitation to standard two-dimensional (2D) perfusion imaging is that the
      narrow elevational beamwidth of 1- or 1.5-D ultrasound transducers provides
      information in only a single slice of tissue, and thus it is difficult to image
      exactly the same plane from study to study. We hypothesize that inhomogeneity in
      vascularization, such as that common in many types of tumors, makes serial
      perfusion estimates inconsistent unless the same region can be imaged repeatedly.
      Our objective was to evaluate error in 2D quantitative perfusion estimation in an
      in vivo sample volume because of differences in transducer positioning. To
      mitigate observed errors due to imaging plane misalignment, we propose and
      demonstrate the application of quantitative 3-dimensional (3D) perfusion imaging.
      We also evaluate the effect of contrast agent concentration and infusion rate on
      perfusion estimates. MATERIALS AND METHODS: Contrast-enhanced destruction
      reperfusion imaging was performed using parametric mapping of refill times and
      custom software for image alignment to compensate for tissue motion. Imaging was
      performed in rats using a Siemens Sequoia 512 imaging system with a 15L8
      transducer. A custom 3D perfusion mapping system was designed by incorporating a
      computer-controlled positioning system to move the transducer in the elevational
      direction, and the Sequoia was interfaced to the motion system for timing of the
      destruction-reperfusion sequence and data acquisition. Perfusion estimates were
      acquired from rat kidneys as a function of imaging plane and in response to the
      vasoactive drug dopamine. RESULTS: Our results indicate that perfusion estimates
      generated by 2D imaging in the rat kidney have mean standard deviations on the
      order of 10%, and as high as 22%, because of differences in initial transducer
      position. This difference was larger than changes in kidney perfusion induced by
      dopamine. With application of 3D perfusion mapping, repeatability in perfusion
      estimated in the kidney is reduced to a standard deviation of less than 3%,
      despite random initial transducer positioning. Varying contrast agent
      administration rate was also observed to bias measured perfusion time, especially
      at low concentrations; however, we observed that contrast administration rates
      between 2.7 * 10(8) and 3.9 * 10(8) bubbles/min provided results that were
      consistent within 3% for the contrast agent type evaluated. CONCLUSIONS: Three
      dimensional perfusion imaging allows a significant reduction in the error caused
      by transducer positioning, and significantly improves the reliability of
      quantitative perfusion time estimates in a rat kidney model. When performing
      perfusion imaging, it is important to use appropriate and consistent contrast
      agent infusion rates to avoid bias.

PMID- 20808233
TI  - Ultrasound molecular imaging of VEGFR2 in a rat prostate tumor model using BR55.
AB  - OBJECTIVES: To evaluate BR55, a new VEGFR2-specific ultrasound contrast agent,
      for imaging prostate tumors in an orthotopic model in the rat. MATERIALS AND
      METHODS: Rat prostate adenocarcinoma were established by injection of G Dunning R
      3327 tumor cells in one lobe of the prostate of Copenhagen rats. Imaging
      experiments were performed with BR55, SonoVue, and streptavidin-functionalized
      microbubbles coupled with an anti-vascular endothelial growth factor receptor 2
      (VEGFR2) antibody using a clinical ultrasound scanner. Contrast enhancement in
      the tumor and healthy prostate was followed over time by intermittent imaging at
      low acoustic power. Signal quantification and statistical analysis were performed
      in the tumor and healthy tissue to compare the behavior of the 3 contrast agents.
      Immunohistochemistry was performed on the prostate and tumor specimen to
      determine the expression of VEGFR2. RESULTS: Comparable contrast enhancement was
      observed in tumors at peak intensity for BR55 and SonoVue. Then, once unbound
      microbubbles had cleared from the circulation, a strong enhancement of the tumor
      was obtained with BR55, whereas no significant microbubble accumulation was
      detected in the healthy prostate tissue. SonoVue microbubbles were rapidly
      eliminated, and no significant binding was observed in the tumor. The tumor to
      prostate ratio calculated after signal quantification was about 20 for the 3
      doses of BR55 tested. The enhancement obtained with BR55 in the tumor was not
      significantly different from the one observed with antibody-coupled streptavidin
      microbubbles. Intense staining for VEGFR2 was detected in the tumor vessels by
      immunohistochemistry. CONCLUSIONS: This study showed that BR55 binding to
      prostate tumors resulted in a strong enhancement of the lesions as early as a few
      minutes after contrast injection, whereas minimal nonspecific accumulation
      occurred in the healthy part of the gland. BR55, like SonoVue, provide
      information on tissue perfusion during the early vascular phase, but BR55 binding
      to the tumoral endothelium allows to gain additional information by highlighting
      the sites of active angiogenesis. The late phase enhancement of the tumor should
      be particularly valuable for prostate cancer detection and for biopsy guidance.

PMID- 20808234
TI  - High-relaxivity magnetic resonance imaging contrast agents. Part 2. Optimization
      of inner- and second-sphere relaxivity.
AB  - RATIONALE AND OBJECTIVES: The observed relaxivity of gadolinium-based contrast
      agents has contributions from the water molecule(s) that bind directly to the
      gadolinium ion (inner-sphere water), long-lived water molecules and exchangeable
      protons that make up the second-sphere of coordination, and water molecules that
      diffuse near the contrast agent (outer-sphere). Inner- and second-sphere
      relaxivity can both be increased by optimization of the lifetimes of the water
      molecules and protons in these coordination spheres, the rotational motion of the
      complex, and the electronic relaxation of the gadolinium ion. We sought to
      identify new high-relaxivity contrast agents by systematically varying the donor
      atoms that bind directly to gadolinium to increase inner-sphere relaxivity and
      concurrently including substituents that influence the second-sphere relaxivity.
      METHODS: Twenty gadolinium-1,4,7,10-tetraazacyclo-dodecane-N,N',N",N'"
      tetraacetato derivatives were prepared and their relaxivity determined in
      presence and absence of human serum albumin as a function of temperature and
      magnetic field. Data was analyzed to extract the underlying molecular parameters
      influencing relaxivity. Each compound had a common albumin-binding group and an
      inner-sphere donor set comprising the 4 tertiary amine N atoms from cyclen, an
      alpha-substituted acetate oxygen atom, 2 amide oxygen atoms, an inner-sphere
      water oxygen atom, and a variable donor group. Each amide nitrogen was
      substituted with different groups to promote hydrogen bonding with second-sphere
      water molecules. RESULTS: Relativities at 0.47 and 1.4 T, 37 degrees C, in serum
      albumin ranged from 16.0 to 58.1 mM(-1)s(-1) and from 12.3 to 34.8 mM(-1)s(-1),
      respectively. The reduction of inner-sphere water exchange typical of amide donor
      groups could be offset by incorporating a phosphonate or phenolate oxygen atom
      donor in the first coordination sphere, resulting in higher relaxivity. Amide
      nitrogen substitution with pendant phosphonate or carboxylate groups increased
      relaxivity by as much as 88% compared with the N-methyl amide analog. Second
      sphere relaxivity contributed as much as 24 and 14 mM(-1)s(-1) at 0.47 and 1.4 T,
      respectively. CONCLUSIONS: Water/proton exchange dynamics in the inner- and
      second-coordination sphere can be predictably tuned by choice of donor atoms and
      second-sphere substituents, resulting in high-relaxivity agents.

PMID- 20808235
TI  - High relaxivity magnetic resonance imaging contrast agents. Part 1. Impact of
      single donor atom substitution on relaxivity of serum albumin-bound gadolinium
      complexes.
AB  - RATIONALE AND OBJECTIVES: The donor atoms that bind to gadolinium in contrast
      agents influence inner-sphere water exchange and electronic relaxation, both of
      which determine observed relaxivity. The effect of these molecular parameters on
      relaxivity is greatest when the contrast agent is protein bound. We sought to
      determine an optimal donor atom set to yield high relaxivity compounds. METHODS:
      A total of 38 gadolinium-1,4,7,10-tetraazacyclo-dodecane-N,N',N'',N'''
      tetraacetato derivatives were prepared and relaxivity was determined in the
      presence and absence of human serum albumin as a function of temperature and
      magnetic field. Each compound had a common albumin-binding group and differed
      only by substitution of different donor groups at one of the macrocycle
      nitrogens. Oxygen-17 isotope relaxometry at 7.05 T was performed to estimate
      water exchange rates. RESULTS: Changing a single donor atom resulted in changes
      in water exchange rates ranging across 3 orders of magnitude. Donor groups
      increased water exchange rate in the order: phosphonate ~ phenolate > alpha
      substituted acetate > acetate > hydroxamate ~ sulfonamide > amide ~ pyridyl ~
      imidazole. Relaxivites at 0.47 and 1.4 T, 37 degrees C, ranged from 12.3 to 55.6
      mM(-1)s(-1) and from 8.3 to 32.6 mM(-1)s(-1) respectively. Optimal relaxivities
      were observed when the donor group was an alpha-substituted acetate. Electronic
      relaxation was slowest for the acetate derivatives as well. CONCLUSIONS: Water
      exchange dynamics and relaxivity can be predictably tuned by choice of donor
      atoms.

PMID- 20808236
TI  - MR signal characteristics of viable and apoptotic human mesenchymal stem cells in
      matrix-associated stem cell implants for treatment of osteoarthritis.
AB  - OBJECTIVE: To compare magnetic resonance (MR) signal characteristics of contrast
      agent-labeled apoptotic and viable human mesenchymal stem cells (hMSCs) in matrix
      associated stem cell implants. METHODS: hMSCs were labeled with Food and Drug
      Administration-approved ferumoxides nanoparticles. One group (A) remained
      untreated whereas a second group (B) underwent mitomycin C-induced apoptosis
      induction. Viability of group A and apoptosis of group B was confirmed by caspase
      assays and terminal dUTP nick-end labeling (TUNEL) stains. Labeled viable hMSCs,
      unlabeled viable hMSCs, labeled apoptotic hMSCs, and unlabeled apoptotic hMSCs (n
      = 7 samples each) in an agarose scaffold were implanted into cartilage defects of
      porcine patellae specimens and underwent MR imaging at 7 T, using T1-weighted
      spin-echo sequences, T2-weighted spin-echo sequences, and T2*-weighted gradient
      echo sequences. Signal-to-noise ratios (SNR) of the implants were calculated and
      compared between different experimental groups using linear mixed regression
      models. RESULTS: Ferumoxides-labeled hMSCs provided a strong negative T2 and T2*
      enhancement. Corresponding SNR data of labeled hMSCs were significantly lower
      compared with unlabeled controls (P < 0.05). Apoptosis induction resulted in a
      significant signal decline of ferumoxides-labeled hMSC transplants on short echo
      time T2-weighted spinecho sequences. SNR data of labeled apoptotic hMSCs were
      significantly lower compared with labeled viable hMSCs (P < 0.05). CONCLUSION:
      Apoptosis of transplanted ferumoxides-labeled stem cells in cartilage defects can
      be visualized noninvasively by a significant signal decline on T2-weighted MR
      images. The described MR signal characteristics may serve as a noninvasive
      outcome measure for the assessment of matrix-associated stem cell implants in
      clinical practice. Additional studies are needed to further enhance the observed
      differences between viable and apoptotic cells, for example, by further
      optimizing the applied MR pulse sequence parameters or intracellular contrast
      agent concentration.

PMID- 20808237
TI  - In vivo differentiation of magnetically labeled mesenchymal stem cells into
      hepatocytes for cell therapy to repair damaged liver.
AB  - OBJECTIVES: It was unclear whether systemically administered mesenchymal stem
      cells (MSCs) labeled with magnetic nanoparticles can transdifferentiate into
      hepatocytes. In the present study, we built a new in vivo murine model for
      monitoring the transdifferentiation of magnetically labeled green fluorescent
      protein (GFP) positive MSCs into albumin-positive hepatocytes, under the carbon
      tetrachloride (CCl4) induced persistent liver damage. We also tracked
      magnetically labeled MSCs by using magnetic resonance imaging (MRI) in vivo.
      MATERIALS AND METHODS: Among the liver damage groups, magnetically labeled GFP
      positive MSCs (group A), GFP-positive MSCs (group B), and saline alone (group C)
      were intravenously injected. In control groups without CCl4 administration
      magnetically labeled GFP-positive MSCs (group D) were infused, whereas nothing
      was given in group E. MRI examinations were performed 24 hours and 4 weeks after
      cell injection in group A, B, and C. Liver-to-muscle contrast-to-noise ratios on
      T2*-weighted MR images were measured. At 4 weeks, 3 serum biologic liver function
      markers were analyzed, and mice in all groups were killed for histologic
      examination. RESULTS: The results showed that migration of transplanted magnetic
      labeled cells to the liver was successfully documented with in vivo MRI. Serum
      liver function markers were changed for all liver damage groups than nondamage
      control groups (P < 0.05), but still insignificant compared with group C (P >
      0.05). Hematoxylin and eosin and Masson staining confirmed the presence of liver
      damage and hepatic fibrosis in group A, B, and C. Positive Prussian blue stained
      cells were highly correlated with GFP-positive cells in group A with an average
      matching rate of 95%. In group D, no iron-GFP-positive cells can be found in the
      liver. Albumin was expressed in (34% +/- 6%) and (35% +/- 7%) of GFP-positive
      cells in group A and B, respectively, and there was no significant difference
      between the 2 groups. CONCLUSIONS: Our data demonstrate that magnetic labeling
      technique synchronized well in GFP expressing MSCs and did not interfere with the
      transdifferentiation process and amending function of MSCs in vivo. Both
      magnetically labeled and unlabeled MSCs appeared to have the potential to
      differentiate into hepatocytes.

PMID- 20808238
TI  - Dynamic contrast-enhanced magnetic resonance imaging evaluation of VX2 carcinoma
      in a rabbit model: comparison of 1.0-M gadobutrol and 0.5-M gadopentetate
      dimeglumine.
AB  - OBJECTIVES: To compare the enhancement characteristics and diagnostic performance
      of 1.0-M gadobutrol with those of 0.5-M gadopentetate dimeglumine in rabbit VX2
      tumor models. MATERIALS AND METHODS: Our study was approved by the Animal Care
      Committee of our hospital. VX2 carcinomas were implanted in both thighs of 14
      rabbits 4 days before magnetic resonance (MR) imaging. The animals underwent 2
      identical MR examinations with 2 different contrast media separated by 8 hours
      with the use of a 3.0 T magnet. T2-, T1- weighted fast spin echo images were
      obtained. Sequential MR imaging with the 3-dimensional-SPGR sequence were
      performed before and at 1, 2, 3, 4, 5, 10, 15, 20, and 30 minutes after injection
      of 0.05 mmol/kg of 1.0-M gadobutrol or 0.5-M gadopentetate dimeglumine. Four
      rabbits without tumor implantation underwent the same MR examinations. Percentage
      enhancement of the tumor was assessed by 2 radiologists in consensus. Three
      different readers without knowledge of the histopathologic results interpreted
      both MR images in terms of presence of tumor. Receiver operating characteristic
      analysis was conducted to compare the diagnostic value of both contrast agents.
      Sensitivities and specificities were also calculated. In addition, lesion-to
      muscle contrast, degree of lesion delineation, and global preferences of the
      readers were determined using a scoring system. RESULTS: A total of 56 VX2 tumors
      were identified by histopathologic review. For the VX2 tumors, the percentage
      enhancement at each time point was consistently higher with injection of 1.0-M
      gadobutrol than with injection of 0.5-M gadopentetate dimeglumine (P < 0.01). The
      area under the receiver operating characteristic curve (Az) values for the use of
      1.0-M gadobutrol-enhanced MR imaging were 0.937, 0.886, and 0.938 for readers 1,
      2, and 3, respectively. The Az values for the use of 0.5-M gadopentetate
      dimeglumine-enhanced MR imaging were 0.908, 0.903, and 0.947. Sensitivities were
      89.3%, 85.7%, and 89.3% for 1.0-M gadobutrol-enhanced MR imaging and 87.5%,
      85.7%, and 89.3% for 0.5-M gadopentetate dimeglumine-enhanced MR imaging.
      Specificities were 87.5%, 75.0%, and 87.5% for 1.0-M gadobutrol-enhanced MR
      imaging and 100%, 81.3%, and 100% for 0.5-M gadopentetate dimeglumine-enhanced MR
      imaging. No significant differences were noted for the Az values, sensitivities,
      and specificities with the use of the 2 contrast agents. Lesion-to-muscle
      contrast, degree of lesion delineation, and global preferences of the readers
      were ranked significantly higher for 1.0-M gadobutrol-enhanced MR imaging in all
      readers (P < 0.001). CONCLUSION: Using a 3.0-T magnet, equivalent doses of 1.0-M
      gadobutrol-enhanced MR imaging showed a superior degree of enhancement for a VX2
      tumor than 0.5-M gadopentetate dimeglumine-enhanced MR imaging, and a significant
      preference for readers was noted for 1.0-M gadobutrol-enhanced MR imaging.

PMID- 20808240
TI  - Rasch analysis of the orientation log and reconsideration of the latent construct
      during inpatient rehabilitation.
AB  - PRIMARY OBJECTIVES: To investigate the measurement properties of the Orientation
      Log (O-Log) and a hybrid scale using Rasch analysis techniques and to explore the
      relations between the items of the 2 scales and the latent linear construct
      modeled in the Rasch analysis. DESIGN: Calibration of data collected weekly
      during inpatient rehabilitation. PARTICIPANTS: Ninety patients admitted for
      rehabilitation after traumatic brain injury. RESULTS: Measure
      reliability/construct validity of the O-Log was too low to justify restructuring
      of disordered rating scales, but the broader set of items in the hybrid scale
      demonstrated good measure reliability/construct validity prior to and following
      rating scale restructuring. Both O-Log and hybrid measures demonstrated
      statistical fit with the linear latent construct, suggesting that orientation and
      memory are only a subset of symptoms in a broader syndrome. CONCLUSIONS:
      Posttraumatic amnesia is by definition a proxy measure of a broader syndrome
      during early recovery and not a measure of the syndrome itself. The results
      suggest that the O-Log cannot reliably measure progress during early recovery.
      Furthermore, the analysis suggests that the construct of posttraumatic amnesia is
      too narrow and should be revisited to improve monitoring of recovery and
      prognostic estimation after brain injury.

PMID- 20808239
TI  - An ultrasound contrast agent targeted to P-selectin detects activated platelets
      at supra-arterial shear flow conditions.
AB  - OBJECTIVES: To evaluate targeting of a microbubble contrast agent to platelets
      under high shear flow using the natural selectin ligand sialyl Lewis. MATERIALS
      AND METHODS: Biotinylated polyacrylamide Sialyl Lewis or biotinylated
      carbohydrate-free polymer (used as a control) were attached to biotinylated
      microbubbles via a streptavidin linker. Activated human platelets were isolated
      and attached to fibrinogen-coated culture dishes. Fibrinogen-coated dishes
      without platelets or platelet dishes blocked by an anti-P-selectin antibody
      served as negative control substrates. Dishes coated by recombinant P-selectin
      served as a positive control substrate. Microbubble adhesion was assessed by
      microscopy in an inverted parallel plate flow chamber, with wall shear stress
      values of 40, 30, 20, 10, and 5 dynes/cm2. The ratio of binding and passing
      microbubbles was defined as capture efficiency. RESULTS: There was no significant
      difference between the groups regarding the number of microbubbles in the fluid
      flow at each shear rate. Sialyl Lewis-targeted microbubbles were binding and
      slowly rolling on the surface of activated platelets and P-selectin-coated dishes
      at all the flow conditions including 40 dynes/cm2. Capture efficiency of targeted
      microbubbles to activated platelets and recombinant P-selectin decreased with
      increasing shear flow: at 5 dynes/cm2, capture efficiency was 16.11% on activated
      platelets versus 21.83% on P-selectin, and, at 40 dynes/cm2, adhesion efficiency
      was still 3.4% in both groups. There was neither significant adhesion of Sialyl
      Lewis-targeted microbubbles to control substrates, nor adhesion of control
      microbubbles to activated platelets or to recombinant P-selectin. CONCLUSIONS:
      Microbubble targeting using sialyl Lewis, a fast-binding ligand to P-selectin, is
      a promising strategy for the design of ultrasound contrast binding to activated
      platelets under high shear stress conditions.

PMID- 20808241
TI  - Injury-specific correlates of combat-related traumatic brain injury in Operation
      Iraqi Freedom.
AB  - BACKGROUND: The prevalence of traumatic brain injury (TBI) has increased during
      the wars in Iraq and Afghanistan compared with 20th century military conflicts.
      The aim of this study was to elucidate injury-specific correlates of combat
      related TBI that have yet to be clearly defined. PARTICIPANTS: Predominately
      Marine US service members who sustained brain injuries in Iraq between March 2004
      and April 2008 identified from clinical records completed in the theater of
      combat operations (n = 2074). MAIN OUTCOME MEASURES: Severity of TBI was
      classified as mild, moderate, or severe. Injury-specific factors, such as injury
      mechanism and type, were abstracted from the clinical records and were compared
      with severity of TBI. RESULTS: Of all TBIs observed in the sample, 89% were mild.
      Higher severity of TBI was associated with an increased likelihood of sustaining
      the injury by gunshot and a lower likelihood of helmet use. Improvised explosive
      devices were associated with a preponderance of mild TBIs, and frequency of
      injuries in locations in addition to the head was highest among those with
      moderate and severe TBIs. Concomitant injuries to the spine/back were associated
      with blast injury mechanisms. CONCLUSIONS: Most incidents of TBI occurring during
      Operation Iraqi Freedom are mild in severity and a result of blast mechanisms.
      Multiple injuries were common, particularly as severity of TBI increased. Further
      research is needed to determine effects of combat-related TBI on rehabilitative
      and adverse health outcomes.

PMID- 20808242
TI  - Common misconceptions about traumatic brain injury among ethnic minorities with
      TBI.
AB  - OBJECTIVE: To investigate common TBI misconceptions among ethnic minorities with
      TBI. DESIGN: Cross-sectional study. SETTING: Level I trauma center. PARTICIPANTS:
      Fifty-eight persons with TBI (28 black and 30 Hispanic) discharged from the
      neurosurgery unit and living in the community. MAIN MEASURE: Forty-item Common
      Misconceptions about Traumatic Brain Injury Questionnaire (CM-TBI). RESULTS:
      Participants displayed misconceptions about approximately one-third of the 40
      items, most regarding amnesia and recovery. Fewer misconceptions were found in
      the brain damage/injury and sequelae categories. A greater percentage of TBI
      misconceptions was associated with having lower education, actively practicing
      religion, being Spanish-speaking and non-US born. After controlling for education
      and actively practicing religion, Spanish-speaking Hispanics reported a greater
      percentage of misconceptions than English-speaking Hispanics and blacks.
      CONCLUSIONS AND IMPLICATIONS: Understanding common TBI misconceptions can assist
      rehabilitation staff in tailoring education programs for racial/ethnic minorities
      including those who are Spanish-speaking. Educational attainment and cultural
      factors should be considered when developing educational interventions for
      persons with TBI from diverse backgrounds. Inaccurate information regarding TBI,
      especially the recovery process, may hinder treatment planning by rehabilitation
      professionals and may result in disappointment and the setting of unrealistic
      goals for persons with injury and their families.

PMID- 20808243
TI  - Biomarkers in nonalcoholic fatty liver disease: a new era in diagnosis and
      staging of disease in children.

PMID- 20808244
TI  - Role of intestinal transporters in neonatal nutrition: carbohydrates, proteins,
      lipids, minerals, and vitamins.
AB  - To support rapid growth and a high metabolic rate, infants require enormous
      amounts of nutrients. The small intestine must have the complete array of
      transporters that absorb the nutrients released from digested food. Failure of
      intestinal transporters to function properly often presents symptoms as "failure
      to thrive" because nutrients are not absorbed and as diarrhea because unabsorbed
      nutrients upset luminal osmolality or become substrates of intestinal bacteria.
      We enumerate the nutrients that constitute human milk and various infant milk
      formulas, explain their importance in neonatal nutrition, then describe for each
      nutrient the transporter(s) that absorbs it from the intestinal lumen into the
      enterocyte cytosol and from the cytosol to the portal blood. More than 100
      membrane and cytosolic transporters are now thought to facilitate absorption of
      minerals and vitamins as well as products of digestion of the macronutrients
      carbohydrates, proteins, and lipids. We highlight research areas that should
      yield information needed to better understand the important role of these
      transporters during normal development.

PMID- 20808245
TI  - An unusual cause of rectal bleeding: intestinal myiasis.

PMID- 20808246
TI  - Serum levels of CK18 M30 and leptin are useful predictors of steatohepatitis and
      fibrosis in paediatric NAFLD.
AB  - BACKGROUND: With the alarming growth in prevalence of paediatric nonalcoholic
      fatty liver disease (NAFLD), there is a need for noninvasive methods of
      stratifying disease severity. Our aim was to evaluate a combination of serum
      biomarkers as a measure of disease activity in paediatric NAFLD. PATIENTS AND
      METHODS: Forty-five children with biopsy-proven NAFLD were enrolled. Caspase
      cleaved CK18 fragments (CK18 M30), hyaluronic acid, leptin, and adiponectin were
      measured in serum using enzyme-linked immunosorbent assays and high-sensitivity C
      reactive protein using a colorimetric assay. RESULTS: Median age was 12.7 years
      (55% boys). Median body mass index z score was 1.7. CK18 M30 levels were
      significantly higher in patients with NAFLD versus controls, median 288 IU/L
      versus 172 IU/L (P < 0.001), and in those with steatohepatitis, median 347 IU/L
      versus simple steatosis (NAFLD activity score < 3), median 191 IU/L (P = 0.006).
      Significant fibrosis (>=F2) could be differentiated from no/minimal fibrosis
      (<F2), median 393 IU/L versus 243 IU/L (P = 0.03). Leptin could distinguish <F2
      from >=F2; 28.9 ng/mL versus 70.1 ng/mL (P = 0.037). Adiponectin, hyaluronic
      acid, and high-sensitivity C-reactive protein did not achieve significance in
      predicting steatohepatitis nor significant fibrosis. CONCLUSIONS: The present
      study combines use of markers for different processes in the development of
      steatohepatitis. Serum biomarkers, especially CK18 M30, are useful in stratifying
      disease severity in paediatric NAFLD.

PMID- 20808247
TI  - Maintenance treatment with proton pump inhibitors for reflux esophagitis in
      pediatric patients: a systematic literature analysis.
AB  - OBJECTIVES: Short-term treatment with a proton pump inhibitor (PPI) is effective
      for healing reflux esophagitis and improving reflux symptoms in pediatric
      patients. Our aim was to assess the efficacy and tolerability of maintenance PPI
      treatment after healing of reflux esophagitis in pediatric patients. MATERIALS
      AND METHODS: Systematic searches of MEDLINE, Excerpta Medica database, and recent
      conference abstracts. RESULTS: Five studies evaluated the efficacy of PPI
      maintenance therapy (6- to 90-month follow-up) in pediatric patients after
      healing of reflux esophagitis. Three found no relapse of reflux esophagitis or
      reflux symptoms during PPI maintenance therapy; however, a low relapse rate
      (1/14) was also found in the placebo group of the only prospective controlled
      study. Two of the 5 studies (both prospective) reported relapse of reflux
      esophagitis at half the original healing dose of omeprazole (7 of 51 patients
      relapsed after 3 months; 8 of 32 within 21 months), which resolved again in most
      patients when the healing dose or higher was given. Four studies evaluated
      relapse of reflux esophagitis and/or reflux symptoms after stopping PPI therapy.
      Reflux symptoms recurred in 18% to 76% of patients across all 4 studies. In the 4
      studies that assessed the safety of PPI maintenance therapy, adverse events were
      infrequent and of low severity. CONCLUSIONS: Pediatric patients with
      gastroesophageal reflux disease and certain chronic comorbidities appear to have
      the greatest need of maintenance PPI treatment after healing of reflux
      esophagitis. In patients requiring maintenance therapy, PPIs appear to be well
      tolerated and effective in maintaining remission of reflux esophagitis and reflux
      symptoms.

PMID- 20808248
TI  - Evaluation of the quality of guidelines for acute gastroenteritis in children
      with the AGREE instrument.
AB  - AIM: The aim of the study was to assess the quality of clinical practice
      guidelines (CPGs) using the Appraisal of Guidelines for Research and Evaluation
      (AGREE) instrument, a validated international tool. MATERIALS AND METHODS: CPGs
      were identified by searching MEDLINE (1966-January 2009) and Embase (1988-January
      2009), CPG databases, and relevant Web sites of agencies and organizations that
      produce and/or endorse guidelines. Included in the study were CPGs in English
      that addressed the management of acute gastroenteritis in children. Retrieved
      CPGs were evaluated with the AGREE instrument for quality assessment by 6
      independent reviewers. AGREE consists of 6 domains for a total of 23 items.
      RESULTS: Nine CPGs were identified. Four were evidence based (EB) and 2 of these
      included tables of evidence. Eight CPGs (88%) scored <50% for "applicability," 7
      (77%) for "stakeholder involvement," and 6 (66%) for "editorial independence."
      Compared with non-EB CPGs, EB CPGs had higher quality scores for all AGREE
      domains, with a better score for "rigor of development" (P < 0.001), "stakeholder
      involvement" and "clarity of presentation" (P < 0.01), and applicability (P <
      0.05). Over time, the quality of guidelines tended to improve. The main
      recommendations of CPGs were similar. However, there were differences in the
      treatment of diarrhea, namely based on the settings and circumstances in which
      CPGs were produced. CONCLUSIONS: The overall quality of CPGs on acute
      gastroenteritis management in children is fair. Aims, target population,
      synthesis of evidence, formulation of recommendations, and clarity of
      presentation are points of strength. Weak issues are applicability, including
      identification of organizational barriers and adherence parameters, and
      cost/efficacy analysis.

PMID- 20808249
TI  - Familial adenomatous polyposis in children and adolescents.
AB  - BACKGROUND: Familial adenomatous polyposis (FAP) is the most common inherited
      polyposis syndrome characterized by the development of hundreds of colorectal
      adenomatous polyps. The aim of this study was to review cases of FAP diagnosed at
      The Children's Hospital of Philadelphia in a 16-year period. METHODS: Medical
      records of patients diagnosed as having FAP between 1990 and 2005 were reviewed.
      The collected data included disease presentation, genetic profile,
      extraintestinal manifestations, surveillance, and treatment. RESULTS: We
      identified 12 patients with FAP. The age range at presentation was 7 to 18 years.
      Seven (68%) patients presented due to symptoms, the most common of which was
      rectal bleeding (6 patients, 86%). The youngest age at which polyps were detected
      was 7 years. Eight patients (67%) had positive family history. Three patients had
      Gardner syndrome and 1 presented in infancy with hepatoblastoma. Four patients
      had adenomatous polyposis coli gene mutation identified. One patient was
      diagnosed as having rectal carcinoma in situ. Six patients (50%) had gastric
      fundic gland polyposis and 6 had duodenal adenomatous changes. Capsule endoscopy
      was performed in 3 patients; 1 had multiple polyps in the duodenum and the
      jejunum. Seven patients (58%) underwent total colectomy with no serious
      complications. CONCLUSIONS: FAP is a rare condition but with significant risk of
      cancer and comorbidity. In this series, patients commonly presented to medical
      attention due to their symptoms. The youngest patient with polyps detected was 7
      years old. We identified 1 patient with rectal cancer in situ and high proportion
      of patients with duodenal adenomatous lesions. Majority of patients underwent
      early colectomy.

PMID- 20808250
TI  - Comparative analysis of FcepsilonRI expression patterns in patients with
      eosinophilic and reflux esophagitis.
AB  - BACKGROUND AND OBJECTIVE: Eosinophilic esophagitis (EoE) is an allergic disease
      of the esophagus. The IgE receptors on immune cells that infiltrate the esophagus
      are poorly defined. The high-affinity receptor for IgE, FcepsilonRI, may play a
      role in EoE. The objective of the present study is to identify and compare the
      IgE receptors in the esophageal epithelium of patients with EoE, reflux
      esophagitis (RE), and normal controls. PATIENTS AND METHODS: A retrospective case
      control study of 62 patients (19 EoE, 22 RE, 21 normal controls) was conducted.
      Biopsies were immunostained for FcepsilonRI, CD23, galectin-3, c-kit, CD1a, and
      langerin. RESULTS: FcepsilonRI was the only IgE receptor present in the
      esophageal epithelium of patients with EoE. The FcepsilonRI-positive cell count
      varied by diagnosis (proximal biopsies EoE 32.6 +/- 19.0 cells/high-power field,
      RE 26.7 +/- 16.6, controls 15.6 +/- 8.3, ANOVA P = 0.005; distal biopsies EoE
      24.2 +/- 16.2, RE 35.7 +/- 27.6, controls 15.3 +/- 8.4, P = 0.006). In the
      proximal esophagus, the FcepsilonRI count was higher in EoE than in controls (P =
      0.006); in the distal esophagus, the FcepsilonRI count was higher in RE than in
      controls (P = 0.004). EoE and RE had similar FcepsilonRI-positive cell counts. A
      subset of FcepsilonRI-positive cells was similar in morphology and distribution
      to Langerhans cells (CD1a and langerin positive). CONCLUSIONS: The presence of
      FcepsilonRI-positive cells in high numbers in the esophageal epithelium implies
      this receptor must be critical in the IgE-mediated activation of immune cells in
      the esophagus. Langerhans cells in the esophageal epithelium appear to express
      FcepsilonRI. The role of Langerhans cells in the pathophysiology of EoE needs to
      be elucidated.

PMID- 20808251
TI  - Remifentanil versus fentanyl for esophagogastroduodenoscopy in children.
AB  - OBJECTIVES: We compared sedation by propofol combined with either fentanyl or
      remifentanil in pediatric outpatients undergoing diagnostic
      esophagogastroduodenoscopy. PATIENTS AND METHODS: Forty-two children scheduled
      for esophagogastroduodenoscopy in our institution were randomly assigned to
      receive 2 mg/kg propofol plus either 1 MUg/kg bolus of fentanyl (group F; n = 20)
      or 0.5 MUg/kg bolus of remifentanil (group R; n = 22). Cardiorespiratory
      parameters, sedation level, adverse effects related to the drugs and/or to the
      procedure, ease of performance for the endoscopist, and time to awakening were
      analyzed. RESULTS: There were no clinically significant changes in hemodynamics.
      Apnea periods >20 seconds and decreases in SaO2 <90% occurred more frequently in
      group R (31.8% vs 0%, P < 0.01, and 27.3% vs 5.0%, P > 0.05, respectively).
      Children in group R had significantly shorter average time to awakening: 9.5 +/-
      5.6 vs 16.5 +/- 10.5 minutes (P = 0.01), and received a significantly lower total
      dose of propofol (P = 0.034). Adverse effects within the first 24 hours
      postprocedure occurred less frequently in group R (P = 0.03). CONCLUSIONS:
      Remifentanil in combination with propofol provides good analgesic and sedative
      effects, which were shorter lasting compared with fentanyl-based sedation, and
      caused fewer delayed adverse effects. The use of remifentanil was associated with
      respiratory depression, emphasizing the need for experienced anesthesiologists.

PMID- 20808252
TI  - Safety and resource utilization by non-small cell lung cancer histology: results
      from the randomized phase III study of pemetrexed plus cisplatin versus
      gemcitabine plus cisplatin in chemonaive patients with advanced non-small cell
      lung cancer.
AB  - INTRODUCTION: A prespecified analysis of the large, randomized, phase III study
      in advanced non-small cell lung cancer showed significant improvement in survival
      for nonsquamous patients treated with pemetrexed/cisplatin versus
      gemcitabine/cisplatin. Selected grade 3/4 toxicities and resource utilization
      favored pemetrexed in the overall population, but detailed safety results by
      histology have not been reported. METHODS: Treated patients were included in this
      analysis of safety by histology. At each cycle, adverse events were assessed, and
      concomitant medications, transfusions, and hospitalizations were recorded.
      Measures were summarized by histology and compared between arms with Fisher's
      exact test. RESULTS: When analyzed by squamous and nonsquamous histology, safety
      and resource utilization for each treatment arm paralleled those of the overall
      population. Selected toxicities did not vary by histology. Concomitant medication
      use and hospitalizations were also very similar to the patterns observed in the
      overall population. CONCLUSIONS: Although previous efficacy analyses showed a
      significant pemetrexed treatment advantage for nonsquamous patients, results of
      this analysis indicate that safety and resource utilization do not vary by
      histology and are consistent with the overall population. The safety and resource
      utilization of patients treated with pemetrexed/cisplatin are predictable,
      reproducible, and consistent with the established favorable safety profile of
      pemetrexed, regardless of histology.

PMID- 20808253
TI  - Phase I/II study of AT-101 with topotecan in relapsed and refractory small cell
      lung cancer.
AB  - INTRODUCTION: AT-101 is an oral, pan Bcl-2 family protein inhibitor that has
      demonstrated activity in small cell lung cancer (SCLC) models. A phase I/II study
      was conducted combining AT-101 with topotecan in relapsed and refractory SCLC.
      METHODS: An open-labeled multicenter phase I/II study was conducted of oral AT
      101 with intravenous topotecan in patients with SCLC who had progressed on prior
      platinum-containing chemotherapy. The phase II portion was a two-stage design,
      and two cohorts of patients, sensitive relapsed and refractory, were analyzed.
      Primary endpoint in the two-stage phase II portion was response rate; secondary
      endpoints were duration of response and time to progression. RESULTS: Thirty-six
      patients were enrolled. The most common toxicities were hematologic, as would be
      expected with topotecan and AT-101. The recommended phase II dose was 40 mg AT
      101 days 1 to 5 with topotecan 1.25 mg/m(2) days 1 to 5 on a 21-day cycle. In the
      sensitive-relapsed cohort (n = 18), there were 0 complete response (CR), three
      partial response (PR), 10 stable disease (SD), and four progressive disease (PD).
      In the refractory cohort (n = 12), there were 0 CR/PR, five SD, and five PD. The
      study did not meet its prespecified endpoints to continue enrollment in the
      second stage of the phase II study. Median time to progression in the sensitive
      relapsed cohort was 17.4 weeks and 11.7 weeks in the refractory cohort.
      CONCLUSIONS: AT-101 can be safely combined with topotecan at a reduced dose of
      1.25 mg/m(2). The response rates observed did not meet the criteria for
      additional enrollment; however, many patients had a best response of SD and the
      median time to progression in both cohorts was favorable. Additional trials of AT
      101 in SCLC are ongoing.

PMID- 20808254
TI  - Complex mutations in the epidermal growth factor receptor gene in non-small cell
      lung cancer.
AB  - INTRODUCTION: Mutation of the epidermal growth factor receptor (EGFR) gene can
      predict the efficacy of EGFR-tyrosine kinase inhibitors. Different mutations have
      been shown to co-occur in a single tumor. However, the frequency of these so
      called "complex mutations" and the efficacy of gefitinib in treating patients
      with these mutations are unclear. METHODS: We investigated the frequency of
      complex mutations in 783 patients with non-small cell lung cancer seen at our
      institutes between April 2006 and May 2009. Mutational analysis was performed
      using the peptide nucleic acid-locked nucleic acid polymerase chain reaction
      clamp method. Gefitinib efficacy was evaluated in patients found to have complex
      mutations. RESULTS: EGFR: mutations were detected in 318 (41%) patients, with 21
      (6.6%) of these individuals having complex mutations. Sixteen of these 21
      patients received gefitinib. The response rate (RR) was 67% (95% confidence
      interval [CI], 35-90%) and median progression-free survival was 12.2 months (95%
      CI, 1.3 months to undeterminable). Analysis of RR according to mutation type
      revealed that patients with deletional mutation in exon 19 (Del-19) and a point
      mutation in exon 21 (L858R) had a better RR (86%, 6 of 7) than those with other
      complex mutation patterns such as a point mutation in exon 18 (G719S) + L858R
      (40%, 2 of 5) (p = 0.2222). The median progression-free survival was also longer
      in these patients (16.5 months; 95% CI, 1.1 months to undeterminable versus 3.8
      months; 95% CI, 0.7-10.0 months) (p = 0.0459). CONCLUSIONS: Complex EGFR
      mutations are not rare. Gefitinib has different efficacy according to the type of
      complex EGFR mutations. Patients with Del-19 and L858R mutations may benefit more
      from gefitinib than other types of complex mutations.

PMID- 20808255
TI  - Efficacy and safety of erlotinib in 1242 East/South-East Asian patients with
      advanced non-small cell lung cancer.
AB  - INTRODUCTION: Erlotinib is an epidermal growth factor receptor tyrosine kinase
      inhibitor that significantly increases survival for patients with previously
      treated advanced non-small cell lung cancer. Epidermal growth factor receptor
      tyrosine kinase inhibitors have been reported to be particularly effective in
      Asian patients and may have a distinct safety profile in this population compared
      with non-Asian patients. We report safety and efficacy data from a subpopulation
      of East/South-East (E/SE) Asian patients enrolled in a global, open-label, phase
      IV trial of erlotinib (Tarceva Lung Cancer Survival Treatment study). METHODS:
      Patients who had previously failed on chemotherapy or radiotherapy, or were
      unsuitable for these treatments, were treated with oral erlotinib (150 mg/d)
      until disease progression or unacceptable toxicity. RESULTS: Best response data
      were available for 1118 E/SE Asian and 4276 non-E/SE Asian patients. The overall
      response rates were 27% versus 10%, respectively (p < 0.0001). The disease
      control rates were 78% versus 66%, respectively (p < 0.0001). Survival data were
      available for 1242 E/SE Asian and 5338 non-E/SE Asian patients. The median
      progression-free survival times were 5.78 months versus 2.92 months, respectively
      (hazard ratio = 0.66, p < 0.0001). The median overall survival times were 14.7
      months versus 6.8 months, respectively (hazard ratio = 0.57, p < 0.0001). One
      year survival rates were 58.3% and 32.7%, respectively. Safety data were
      available for 1242 E/SE Asian patients. Seventeen percent of these patients
      experienced one or more erlotinib-related adverse event (AE) (other than the most
      frequently occurring AEs prespecified in the protocol) and 2% experienced an
      erlotinib-related serious AE. Dose reductions were reported for 171 (14%)
      patients. CONCLUSION: Erlotinib is an effective and well-tolerated treatment for
      Asian patients with advanced non-small cell lung cancer.

PMID- 20808257
TI  - Colorectal cancer screening in primary care: translating research into practice.
AB  - BACKGROUND: Colorectal cancer (CRC) screening is recommended for all adults 50 to
      75 years old, yet only slightly more than one-half of eligible people are current
      with screening. Because CRC screening is usually initiated upon recommendations
      of primary care physicians, interventions in these settings are needed to improve
      screening. OBJECTIVES: To assess the impact of a quality improvement intervention
      combining electronic medical record based audit and feedback, practice site
      visits for academic detailing and participatory planning, and "best-practice"
      dissemination on CRC screening in primary care practice. RESEARCH DESIGN: Two
      year group randomized trial. SUBJECTS: Physicians, midlevel providers, and
      clinical staff members in 32 primary care practices in 19 States caring for
      68,150 patients 50 years of age or older. MEASURES: Proportion of active patients
      up-to-date (UTD) with CRC screening (colonoscopy within 10 years, sigmoidoscopy
      within 5 years, or at home fecal occult blood testing within 1 year) and having
      screening recommended within past year among those not UTD. RESULTS: Patients 50
      to 75 years in intervention practices exhibited significantly greater improvement
      (from 60.7% to 71.2%) in being UTD with CRC screening than patients in control
      practices (from 57.7% to 62.8%), the adjusted difference being 4.9% (95%
      confidence interval, 3.8%-6.1%). Recommendations for screening also increased
      more in intervention practices with the adjusted difference being 7.9% (95%
      confidence interval, 6.3%-9.5%). There was wide interpractice variation in CRC
      screening throughout the intervention. CONCLUSIONS: A multicomponent quality
      improvement intervention in practices that use electronic medical record can
      improve CRC screening.

PMID- 20808256
TI  - Does it matter where you go for breast surgery?: attending surgeon's influence on
      variation in receipt of mastectomy for breast cancer.
AB  - BACKGROUND: Concerns about the use of mastectomy and breast reconstruction for
      breast cancer have motivated interest in surgeon's influence on the variation in
      receipt of these procedures. OBJECTIVES: To evaluate the influence of surgeons on
      variations in the receipt of mastectomy and breast reconstruction for patients
      recently diagnosed with breast cancer. METHODS: Attending surgeons (n = 419) of a
      population-based sample of breast cancer patients diagnosed in Detroit and Los
      Angeles during June 2005 to February 2007 (n = 2290) were surveyed. Respondent
      surgeons (n = 291) and patients (n = 1780) were linked. Random-effects models
      examined the amount of variation due to surgeon for surgical treatment.
      Covariates included patient clinical and demographic factors and surgeon
      demographics, breast cancer specialization, patient management process measures,
      and attitudes about treatment. RESULTS: Surgeons explained a modest amount of the
      variation in receipt of mastectomy (4%) after controlling for patient clinical
      and sociodemographic factors but a greater amount for reconstruction (16%).
      Variation in treatment rates across surgeons for a common patient case was much
      wider for reconstruction (median, 29%; 5th-95th percentile, 9%-65%) then for
      mastectomy (median, 18%; 5th-95th percentile, 8% and 35%). Surgeon factors did
      not explain between-surgeon variation in receipt of treatment. For
      reconstruction, 1 surgeon factor (tendency to discuss treatment plans with a
      plastic surgeon prior to surgery) explained a substantial amount of the between
      surgeon variation (31%). CONCLUSION: Surgeons have largely adopted a consistent
      approach to the initial surgery options. By contrast, the wider between-surgeon
      variation in receipt of breast reconstruction suggests more variation in how
      these decisions are made in clinical practice.

PMID- 20808258
TI  - Cost-effectiveness of a quality improvement collaborative focusing on patients
      with diabetes.
AB  - OBJECTIVE: To investigate the lifelong health effects, costs, and cost
      effectiveness of a quality improvement collaborative focusing on improving
      diabetes management in an integrated care setting. STUDY DESIGN AND METHODS:
      Economic evaluation from a healthcare perspective with lifetime horizon alongside
      a nonrandomized, controlled, before-after study in the Netherlands. Analyses were
      based on 1861 diabetes patients in 6 intervention and 9 control regions,
      representing 37 general practices and 13 out-patient clinics. Change in the
      United Kingdom Prospective Diabetes Study score, remaining lifetime, and costs
      per quality-adjusted life year gained were calculated. Probabilistic life tables
      were constructed using the United Kingdom Prospective Diabetes Study risk engine,
      a validated diabetes model, and nonparametric bootstrapping of individual patient
      data. RESULTS: Annual United Kingdom Prospective Diabetes Study risk scores
      reduced for cardiovascular events (hazard ratio: 0.83 and 0.98) and
      cardiovascular mortality (hazard ratio: 0.78 and 0.88) for men and women,
      respectively. Life expectancy improved by 0.97 and 0.76 years for men and women,
      and quality-adjusted life years by 0.44 and 0.37, respectively. Higher life
      expectancy in the intervention group increased lifelong costs by &OV0556;860 for
      men and &OV0556;645 for women. Initial program costs were about &OV0556;22 per
      patient. The incremental costs per quality-adjusted life year were &OV0556;1937
      for men and &OV0556;1751 for women compared with usual care costs. There is a
      probability >95% that the collaborative is cost-effective, using a threshold of
      &OV0556;20,000 per quality-adjusted life year. CONCLUSION: Optimizing integrated
      and patient-centered diabetes care through a quality-improvement collaborative is
      cost-effective compared with usual care.

PMID- 20808259
TI  - Controlling costs without compromising quality: paying hospitals for total knee
      replacement.
AB  - BACKGROUND: Unit costs of health services are substantially higher in the United
      States than in any other developed country in the world, without a
      correspondingly healthier population. An alternative payment structure,
      especially for high volume, high cost episodes of care (eg, total knee
      replacement), is needed to reward high quality care and reduce costs. METHODS:
      The National Inpatient Sample of administrative claims data was used to measure
      risk-adjusted mortality, postoperative length-of-stay, costs of routine care,
      adverse outcome rates, and excess costs of adverse outcomes for total knee
      replacements performed between 2002 and 2005. Empirically identified inefficient
      and ineffective hospitals were then removed to create a reference group of high
      performance hospitals. Predictive models for outcomes and costs were recalibrated
      to the reference hospitals and used to compute risk-adjusted outcomes and costs
      for all hospitals. Per case predicted costs were computed and compared with
      observed costs. RESULTS: Of the 688 hospitals with acceptable data, 62 failed to
      meet effectiveness criteria and 210 were identified as inefficient. The remaining
      416 high-performance hospitals had 13.4% fewer risk-adjusted adverse outcomes
      (4.56%-3.95%; P < 0.001; chi) and 9.9% lower risk-adjusted total costs ($12,773
      $11,512; P < 0.001; t test) than all study hospitals. Inefficiency accounted for
      96% of excess costs. CONCLUSIONS: A payment system based on the demonstrated
      performance of effective, efficient hospitals can produce sizable cost savings
      without jeopardizing quality. In this study, 96% of total excess hospital costs
      resulted from higher routine costs at inefficient hospitals, whereas only 4% was
      associated with ineffective care.

PMID- 20808260
TI  - Impact of predialysis therapeutic practices on patient outcomes during the first
      year of dialysis: the Pharmacoepidemiologic AVENIR study.
AB  - BACKGROUND: Studies evaluating patient outcomes in dialysis as a function of
      quality of predialysis therapeutic care are lacking. OBJECTIVE: To evaluate the
      association of quality of predialysis therapeutic practices with survival and
      hospitalization during the first year of dialysis. RESEARCH DESIGN: The AVantagE
      de la Nephroprotection dans l'Insuffisance Renale study was an observational
      cohort study. Cox models explored the association between quality of therapeutic
      practices and survival over the first year whereas logistic regression measured
      the association with total duration of hospitalization (0 to 6 d, >=7 d) among
      surviving patients at 1 year. SUBJECTS: All adult patients with chronic kidney
      disease starting dialysis in Lorraine (France) between 2005 and 2006. MEASURES:
      The appropriateness of therapeutic practices was evaluated with reference to
      current guidelines covering 5 aspects of chronic kidney disease:
      hypertension/proteinuria, anemia, bone disease, metabolic acidosis, and
      dyslipidemia. Each patient was then assigned a quality of therapeutic practices
      rating (high, moderate, or poor) depending on the number of aspects appropriately
      managed. RESULTS: Quality of predialysis therapeutic practices was high in 18.2%
      of the 566 included patients, moderate in 62.5%, and poor in 19.3%. In
      multivariate analysis, the higher the quality of practices, the better the
      survival rate during the first year of dialysis [High: hazard ratio (HR) 1;
      moderate: HR 1.56, P=0.09; poor: HR 1.95, P=0.02]. Conversely, quality of
      therapeutic practices was not associated with duration of hospitalization among
      the 390 surviving patients at 1 year. CONCLUSION: This study suggests that
      quality of predialysis therapeutic practices is positively associated with
      survival during the first year of dialysis.

PMID- 20808261
TI  - Myocardial ischemia in patients with dilated cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) is characterized by ventricular chamber enlargement
      and systolic dysfunction with normal ventricular wall thickness. More recent
      studies have shown that the coronary microcirculation may be directly affected in
      cardiomyopathies. Left ventricular regional myocardial perfusion, wall motion,
      and metabolism abnormalities are often present in patients with DCM. These data
      support the possibility that myocardial ischemia may play an important role in
      the development of DCM and have important prognostic value in patients with DCM.
      We need to pay attention to the assessment of myocardial blood flow and
      myocardial ischemia in patients with DCM. Furthermore, anti-ischemic therapy may
      improve left ventricular function and clinical outcomes in patients with heart
      failure resulted from DCM.

PMID- 20808263
TI  - In situ protection against islet allograft rejection by CTLA4Ig transduction.
AB  - BACKGROUND: Immunosuppression focused at or near the graft site would reduce the
      need for systemic immunosuppression thus educing fewer side effects. We
      investigated whether locally produced CTLA4Ig, mediated by adenovirus (Adv)
      transduction of mouse islets, would protect allografts and whether such
      immunosuppression would remain localized. METHODS: Adv-CTLA4Ig- or Adv-control
      transduced islets were grafted under the kidney capsule of fully allogeneic
      diabetic mice. CTLA4Ig secreted from the grafted islets was detected by enzyme
      immunoassay of blood or immunohistochemistry of graft sections. Graft survival
      was monitored by blood glucose measurement. Histologic scores of graft sections
      stained with Gomori aldehyde fuchsin to detect insulin granules or hematoxylin
      eosin to detect inflammation were used to compare grafts placed at different
      sites within the same mouse. RESULTS: Adv-CTLA4Ig-transduced islet grafts
      secreted CTLA4Ig that was detected transiently in the circulation but
      persistently at the graft site. Survival of these grafts was significantly
      enhanced compared with control Adv-transduced and untransduced grafts. The kidney
      graft site availed elucidation of the site of action of CTLA4Ig. Histologic
      scores indicated that CTLA4Ig-producing grafts were protected by comparison with
      control grafts on the contralateral kidney. Hence, graft protection was not
      attributable to general systemic immunosuppression. Indeed, survival of CTLA4Ig
      producing grafts was enhanced over control grafts placed at the opposite pole of
      the same kidney, indicating that graft protection was not solely due to
      inhibition of priming in the common draining lymph nodes. CONCLUSIONS: Islet
      allografts are protected by locally produced CTLA4Ig-disrupting immune
      interactions at the effector site.

PMID- 20808262
TI  - Tissue-specific DNA methylation of the human prodynorphin gene in post-mortem
      brain tissues and PBMCs.
AB  - OBJECTIVE: Dynorphins, the endogenous ligands for the kappa opioid receptor, are
      implicated in neuropsychiatric disorders through modulation of basal and stimuli
      induced dopaminergic, glutamatergic, and serotonergic tones. Expression of the
      prodynorphin gene (PDYN) is critical for rewarding properties of drugs of abuse
      and stress-induced responses. Epigenetic factors, such as DNA methylation, play
      an important role in modulation of gene expression. METHODS: We analyzed DNA
      methylation patterns of three CpG-rich regions of PDYN, a CpG island, and cluster
      A in the proximal promoter, and cluster B in coding exon 4, by bisulfite
      sequencing of DNA from the caudate and anterior cingulate cortex from post-mortem
      brain of 35 individuals (22 HIV seropositive), and in peripheral blood
      mononuclear cells from 21 of these individuals. RESULTS: We found remarkably
      similar patterns of methylation across CpG sites in these tissues. However, there
      were tissue-specific differences in methylation levels (P=0.000001) of the CpG
      island: higher levels in peripheral blood mononuclear cells (82%) than in the
      brain tissues, the caudate (62%), and the anterior cingulate cortex (44%). But
      there was higher PDYN expression in the caudate than in the anterior cingulate
      cortex. In contrast, cluster A near the transcription start site is
      hypomethylated. CONCLUSION: This DNA methylation profile of the PDYN gene is
      typical for primary responsive genes with regulatory elements for both basal and
      tissue-specific transcription. Our findings provide a rationale for further
      studies of the role of other epigenetic factors in the regulation of PDYN
      expression in individuals with psychiatric and neurological disorders.

PMID- 20808264
TI  - Effects of pravastatin on murine chronic graft-versus-host disease.
AB  - BACKGROUND: Chronic graft-versus-host disease (CGVHD) is a serious and
      increasingly common complication after allogeneic (allo) hematopoietic stem-cell
      transplantation, but currently available therapies have demonstrated limited
      efficacy. Furthermore, the statins have been reported to be effective in various
      immune-mediated disease models, but their therapeutic potentials versus CGVHD
      have not been determined. METHODS: We used a B10.D2->BALB/c model of CGVHD, which
      differs at minor histocompatibility loci, to address the therapeutic effect of
      statins on the development of CGVHD. Pravastatin (PST, 30 mg/kg/day) was
      intraperitoneally injected for 5 days per week from the day of transplantation
      until 4 weeks after allo hematopoietic stem-cell transplantation. RESULTS: The
      onset of clinical cutaneous GVHD was significantly slower in PST-treated
      recipients than in allo-controls (36 days vs. 25 days, respectively, P<0.05), and
      pathologic changes in skin disease confirmed this clinical result. Animals
      injected with PST showed less submucosal fibrosis in lungs than allo-controls. In
      addition, collagen deposition in skin and lungs was markedly attenuated by PST
      treatment. PST also significantly reduced protein concentrations and numbers of
      inflammatory and epithelial cells in bronchoalveolar lavage fluid. Significantly
      lower numbers of donor CD11b and CD4, but not CD8 cells, were observed in skin
      and bronchoalveolar lavage fluid after PST treatment. The protein concentrations
      of monocyte chemoattractant protein-1 (MCP-1) and regulated on activation normal
      T cell expressed and secreted (RANTES) in skin and lungs were substantially
      reduced in PST-treated animals when compared with allo-controls. CONCLUSIONS:
      This study suggests that the CGVHD-protecting effect of PST involves the down
      regulation of chemokines and the reduction of collagen synthesis.

PMID- 20808265
TI  - Impact of HLA compatibility on lung transplant survival and evidence for an HLA
      restriction phenomenon: a collaborative transplant study report.
AB  - BACKGROUND: Data concerning the impact of human leukocyte antigen (HLA)
      compatibility on lung transplant survival rates are limited. METHODS: Using the
      Collaborative Transplant Study database, 5-year graft outcome according to HLA
      mismatch was examined in 8020 deceased donor lung transplants performed during
      1989 to 2009. RESULTS: Graft survival rates showed a stepwise decrease as the
      combined number of HLA-A+B+DR mismatches increased from one to six (P<0.001).
      Surprisingly, the 28 grafts with 0 mismatches at all 3 loci had a 1-year survival
      rate of only 49.7%, significantly lower than for 1, 2, 3, 4, 5, or 6 mismatches
      (P=0.002, <0.001, <0.001, <0.001, 0.002, and 0.003, respectively). Multivariate
      regression analysis confirmed that, paradoxically, transplantation of grafts with
      zero HLA-A+B+DR mismatches was associated with a 19% increase in relative risk of
      failure. Donor lung preservation for up to 12 hr was not associated with inferior
      graft survival versus shorter preservation times (P=0.60). CONCLUSIONS: Our data
      show that a high number of HLA mismatches or zero mismatches impacts unfavorably
      on lung transplant survival.

PMID- 20808266
TI  - Aggressive behavior of nonmelanotic skin cancers in solid organ transplant
      recipients.
AB  - BACKGROUND: The increased incidence of skin cancers in solid organ transplant
      recipients (OTR) has been well established. However, our understanding of the
      potential aggressive behavior of these cancers has been largely based on the
      findings of multiple different studies analyzing isolated indicators of
      aggressive behavior. The purpose of this study was to determine the
      aggressiveness of nonmelanotic skin cancers in a large transplant population
      compared with an immunocompetent control population with similar cancers.
      METHODS: Immunosuppressed transplanted patients and an immunocompetent control
      group matched in size with squamous cell carcinoma (SCC) or basal cell carcinoma
      (BCC) were evaluated for the factors of aggressiveness. A retrospective chart
      review was performed. Data obtained included transplant type, number of cancers,
      local recurrence rate, lymph node involvement, lymphatic invasion, perineural
      invasion, deep spread, subsequent treatment with radiation or chemotherapy, and
      death from disease. RESULTS: Three hundred seven patients had SCC (OTR: 153,
      control: 154), and 246 patients had BCC (OTR: 123, control: 123). SCC in OTR was
      significantly more likely to have an increased number of primary tumors, deep
      tissue spread, perineural and lymphatic invasion, recurrence, and need for
      radiation or chemotherapy. BCC in OTR was not associated with more aggressive
      disease when compared with controls with BCC. CONCLUSIONS: SCC in OTR behaves
      significantly more aggressively than in immunocompetent patients. BCC in the OTR
      population does not seem to act more aggressively.

PMID- 20808267
TI  - [2011, the year of France at the ECR. ECR 2011 program].

PMID- 20808268
TI  - [CT imaging features of colitis in neutropenic patients].
AB  - Colitis in neutropenic patients presents with non-specific clinical findings
      including abdominal pain, fever, diarrhea and abnormal liver function tests. Four
      diagnoses are relatively more frequent: neutropenic enterocolitis,
      pseudomembranous colitis, intestinal GVHD and CMV colitis. Knowledge of their
      respective imaging features combined with epidemiological data frequently leads
      to the correct diagnosis. The purpose of this paper is to illustrate the imaging
      features of colitis in neutropenic patients.

PMID- 20808269
TI  - [Ultrasound imaging of Dupuytren's contracture].
AB  - Dupuytren's contracture is characterized by two underlying lesions, nodules and
      cords. These involve the palmar fascia at the distal palmar crease, especially at
      the level of the third and fourth rays with progressive disabling finger
      contracture. The superficial palmar aponeurosis appears as a thin echogenic
      lamellar structure overlying the flexor tendons. The demonstration of hypoechoic
      bands adhering to the marging of the flexor tendons and deep surface of the
      dermis appears to be pathognomonic of the disease. Compared to tendons, early
      nodules are hypoechoic and typically hypervascular whereas older nodules are iso-
      to hyperechoic, without hypervascular Doppler signal. Ultrasound can sometimes
      demonstrate arterial encasement by fibrous or scarring tissue. Ultrasound
      therefore is very useful for the differential diagnosis of pathologies involving
      the palmar surface of the hand, for the early detection of Dupuytren's
      contracture, and for the detection of complication, especially vascular. These
      data may have an impact on management.

PMID- 20808270
TI  - [MRI evaluation of residual breast carcinoma after neoadjuvant chemotherapy].
AB  - PURPOSE: This study aims to evaluate the sensibility and specificity of MRI in
      the detection and size measuring of residual breast cancer in patients treated
      with neoadjuvant chemotherapy before surgery. PATIENTS AND METHODS: This is a
      retrospective study of 32 women, who underwent breast MRI before and after
      neoadjuvant treatment. MRI has been confronted to surgical pathology results.
      RESULTS: The sensibility of MRI to assess pathologic Complete Response (no
      invasive residual tumor) was excellent (100%) but the specificity was low
      (55,5%). There was no false negative case and four false positive cases (Two
      ductal carcinomas in situ and two scars-like fibrosis). When MRI outcomes were
      compared with the presence or absence of invasive or in situ residual carcinoma,
      only one false negative case was noticed (one "in situ" residual tumor). The
      correlation between tumor size measured by MRI and histopathology was low
      (r=0,32). Underestimations of tumor size were due to non-continuous tumor
      regression or invasive lobular carcinoma or association of invasive carcinoma and
      intra ductal breast cancer. Over estimations of tumor size were due to
      chemotherapy-induced changes. CONCLUSION: MRI is a sensitive but poorly specific
      method to assess the pathological complete response after neoadjuvant
      chemotherapy. Estimation of tumor size and detection of isolated residual in situ
      carcinoma are fare. Therefore, surgical intervention remains necessary whatever
      the MRI outcomes.

PMID- 20808271
TI  - [Ultrasound evaluation of the greater occipital nerve].
AB  - PURPOSE: To demonstrate the appearance of the greater occipital nerve on
      ultrasound. MATERIALS AND METHODS: The greater occipital nerve was evaluated in
      21 patients (9 males-12 females; mean age=52 years, range: 20-71; mean
      weight=74.5kg, range: 50-125) at the time of carotid duplex ultrasound. All
      examinations were preformed by the same sonographer using a single ultrasound
      unit. The anatomical landmark used to locate the nerve was the inferior obliquus
      capitis muscle. MRI and CT images were available in two cases and anatomical
      cadaver sections were also available. RESULTS: The greater occipital nerve could
      be identified at the level of the inferior obliquus capitis muscle in 90.47%
      (19/21) of cases, even in obese patients. In three slender patients (14.38%), the
      nerve could be identified at the level of the trapezius aponeurosis and next to
      the V3 segment of the vertebral artery. The mean anteroposterior diameter of the
      nerve at the level of the inferior obliquus capitis muscle was 1.65mm (range:
      1.14mm-2.8mm). CONCLUSION: The greater occipital nerve could be detected at the
      level of its first genu by ultrasound in 90% of patients, even in obese patients.

PMID- 20808272
TI  - [Dental ankylosis diagnosed by CT with tridimensional reconstructions].
AB  - The etiology of unerupted teeth often is difficult to establish. It may relate to
      abnormal orientation of the tooth bud, an anatomical obstacle, pathology of the
      dental sac or ankylosis. The ankylosis process and diagnosis are analyzed in this
      clinical series. Ankylosis and its underlying physiological process are
      abundantly described in the literature. Nonetheless, diagnosis remains difficult
      to achieve. Clinical evaluation and complementary radiographic techniques such as
      dental radiographs and orthopantomogram are considered by some authors as poorly
      reliable. These clinical examinations based on a series of subjective criteria
      cannot be performed on unerupted teeth. In a series of patients with unerupted or
      retained teeth of undetermined etiology or with traction failure, 15 were
      diagnosed with ankylosis. The diagnosis of ankylosis could not be achieved based
      on clinical or radiographic evaluation and required CT imaging. Source images
      along with tridimensional reconstructed images were evaluated using the MVS
      software (Hospices Civils of Lyon). The radicular volume involved by ankylosis
      could be measured and its exact location on the tooth could be demonstrated. This
      imaging technique with tridimensional reconstruction provided positive diagnosis
      of ankylosis.

PMID- 20808273
TI  - [Rhinocerebral infections in immunosuppressed patients with hematological
      disorders].
AB  - Invasive rhinosinusitis, occurring almost exclusively in immunosuppressed
      patients, is defined by the presence of local inflammation with vascular and
      osseous necrosis with extensive soft tissue extension. Imaging and
      bacteriological and even histological (mycelial filaments) criteria have been
      established. Because it can evolve to death in patients with hematological
      disorders, accurate diagnosis is important but difficult to achieve due to the
      non-specific nature of signs and symptoms. Imaging plays an important role with
      CT of the paranasal sinuses and MR imaging of the brain for early diagnosis and
      treatment in order to improve prognosis. We will present the imaging features of
      three cases of rhinocerebral infections, with two cases of fungal infection and
      one case of invasive bacterial sinus infection.

PMID- 20808274
TI  - [Dropped stone: a case report].

PMID- 20808275
TI  - [Cyst of the symphysis pubis].

PMID- 20808276
TI  - [Unilateral pulmonary artery agenesis: a case report].

PMID- 20808277
TI  - [Splenogonadal fusion in an adult with intra-abdominal cryptorchidism].

PMID- 20808278
TI  - [Intraspinal bursitis secondary to Baastrup's disease: a rare cause of radicular
      compression].

PMID- 20808279
TI  - [Isolated cerebellar syndrome due to ventrolateral thalamic nucleus infarction].

PMID- 20808280
TI  - [Answer to may e-quid. Multiple xanthomas as the presenting sign of type IIa
      hypercholesterolemia].

PMID- 20808282
TI  - A multiprotein complex necessary for both transcription and DNA replication at
      the beta-globin locus.
AB  - DNA replication, repair, transcription and chromatin structure are intricately
      associated nuclear processes, but the molecular links between these events are
      often obscure. In this study, we have surveyed the protein complexes that bind at
      beta-globin locus control region, and purified and characterized the function of
      one such multiprotein complex from human erythroleukemic K562 cells. We further
      validated the existence of this complex in human CD34+ cell-derived normal
      erythroid cells. This complex contains ILF2/ILF3 transcription factors, p300
      acetyltransferase and proteins associated with DNA replication, transcription and
      repair. RNAi knockdown of ILF2, a DNA-binding component of this complex,
      abrogates the recruitment of the complex to its cognate DNA sequence and inhibits
      transcription, histone acetylation and usage of the origin of DNA replication at
      the beta-globin locus. These results imply a direct link between mammalian DNA
      replication, transcription and histone acetylation mediated by a single
      multiprotein complex.

PMID- 20808283
TI  - NBR1 is a new PB1 signalling adapter in Th2 differentiation and allergic airway
      inflammation in vivo.
AB  - Allergic airway inflammation is a disease in which T helper 2 (Th2) cells have a
      critical function. The molecular mechanisms controlling Th2 differentiation and
      function are of paramount importance in biology and immunology. Recently, a
      network of PB1-containing adapters and kinases has been shown to be essential in
      this process owing to its function in regulating cell polarity and the activation
      of critical transcription factors. Here, we show in vivo data showing that T-cell
      specific NBR1-deficient mice show impaired lung inflammation and have defective
      Th2 differentiation ex vivo with alterations in T-cell polarity and the selective
      inhibition of Gata3 and nuclear factor of activated T c1 activation. These
      results establish NBR1 as a novel PB1 adapter in Th2 differentiation and asthma.

PMID- 20808284
TI  - The potential functions of primary microRNAs in target recognition and
      repression.
AB  - Major RNA products of a microRNA (miRNA) gene--the long primary transcript (pri
      miRNA), the ~70-nucleotide (nt) precursor miRNA (pre-miRNA), and the ~21-nt
      mature miRNA--all contain the same sequence required for target gene recognition.
      Thus, it is intrinsically difficult to discern the contribution of individual RNA
      species or to rule out a function of miRNA precursor species in target
      repression. Here, we describe a novel approach to dissect the functional
      contribution of pri-miRNA without compromising important cellular pathways. We
      show that pri-let-7 has a direct function in target repression in the absence of
      properly processed mature let-7. Moreover, we show that loop nucleotides provide
      regulatory controls of the activity of pri-let-7 by modulating interactions
      between pri-let-7 and target RNAs in vitro and in vivo. Finally, we show that
      human let-7a-3 pri-miRNA can directly interact with target mRNAs. These findings
      illustrate that the regulatory information encoded in structured pri-miRNAs may
      be translated into function through direct interactions with target mRNAs.

PMID- 20808285
TI  - The role of Rho protein signaling in hypertension.
AB  - Arterial hypertension is a common health problem that affects 25% of the adult
      population in industrialized societies, and is a major risk factor for myocardial
      infarction and stroke. However, the pathogenesis of hypertension, as well as the
      basic mechanisms of blood-pressure control, are insufficiently understood.
      Although the development of hypertension is complex, involving many different
      mechanisms, including dysregulation of the autonomic nervous system, renal
      function, and the balance between water and electrolytes, and increased vascular
      tone and the resulting rise in peripheral vascular resistance are major
      determinants of the elevated arterial pressure in hypertension. Since the
      discovery of the essential role of RhoA and its downstream target, Rho kinase, in
      the regulation of vascular tone, as well as the antihypertensive effect of a Rho
      kinase inhibitor, much evidence has accumulated to implicate activation of Rho
      family proteins in the pathogenesis of hypertension. RhoA remains the most
      analyzed member of the Rho proteins in the context of vascular physiology and
      hypertension, but evidence is accumulating that also points to a role of Rac1 in
      arterial pathophysiology. In this Review, we discuss progress in our
      understanding of the role of Rho proteins and their regulators in the
      pathogenesis of high blood pressure.

PMID- 20808287
TI  - Helper-dependent adenoviral vectors are superior in vitro to first-generation
      vectors for endothelial cell-targeted gene therapy.
AB  - Arterial endothelial cells (EC) are attractive targets for gene therapy of
      atherosclerosis because they are accessible to hematogenous and catheter-based
      vector delivery and overlie atherosclerotic plaques. Vector-mediated expression
      in EC-of proteins that mediate cholesterol transfer out of the artery wall and
      decrease inflammation could prevent and reverse atherosclerosis. However,
      clinical application of this strategy is limited by lack of a suitable gene
      transfer vector. First-generation adenovirus (FGAd) is useful for EC gene
      transfer in proof-of-concept studies, but is unsuitable for atheroprotective
      human gene therapy because of limited duration of expression and proinflammatory
      effects. Moreover, others have reported detrimental effects of FGAd on critical
      aspects of EC physiology including proliferation, migration, and apoptosis. Here,
      we investigated whether helper-dependent adenovirus (HDAd) either alone or
      expressing an atheroprotective gene [apolipoprotein A-I (apoA-I)] could
      circumvent these limitations. In contrast to control FGAd, HDAd did not alter any
      of several critical EC physiologic functions (including proliferation, migration,
      apoptosis, metabolic activity, and nitric oxide (NO) production) and did not
      stimulate proinflammatory pathways [including expression of intercellular
      adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and
      interleukin-6 (IL-6)]. Expression of apoA-I by HDAd reduced EC VCAM-1 expression.
      HDAd is a promising vector and apoA-I is a promising gene for atheroprotective
      human gene therapy delivered via EC.

PMID- 20808288
TI  - Minimal RB-responsive E1A promoter modification to attain potency, selectivity,
      and transgene-arming capacity in oncolytic adenoviruses.
AB  - Oncolytic adenoviruses are promising anticancer agents due to their ability to
      self-amplify at the tumor mass. However, tumor stroma imposes barriers difficult
      to overcome by these agents. Transgene expression is a valuable strategy to
      counteract these limitations and to enhance antitumor activity. For this purpose,
      the genetic backbone in which the transgene is inserted should be optimized to
      render transgene expression compatible with the adenovirus replication cycle and
      to keep genome size within the encapsidation size limit. In order to design a
      potent and selective oncolytic adenovirus that keeps intact all the viral
      functions with minimal increase in genome size, we inserted palindromic E2F
      binding sites into the endogenous E1A promoter. The insertion of these sites
      controlling E1A-Delta24 results in a low systemic toxicity profile in mice.
      Importantly, the E2F-binding sites also increased the cytotoxicity and the
      systemic antitumor activity relative to wild-type adenovirus in all cancer models
      tested. The low toxicity and the increased potency results in improved antitumor
      efficacy after systemic injection and increased survival of mice carrying tumors.
      Furthermore, the constrained genome size of this backbone allows an efficient and
      potent expression of transgenes, indicating that this virus holds promise for
      overcoming the limitations of oncolytic adenoviral therapy.

PMID- 20808286
TI  - Transplantation tolerance through mixed chimerism.
AB  - The major factors that limit the success of organ transplantation are the host
      immune response to the foreign graft and the adverse effects of the chronic
      immunosuppressive therapy required to suppress this immune response. Deliberately
      establishing tolerance towards the donor tissue by reprogramming the immune
      system of the recipient thus holds great promise in improving organ transplant
      survival and eliminating the untoward effects of chronic drug therapy. The
      transplantation of donor bone marrow into recipients who are appropriately
      conditioned to allow development of either full or mixed chimerism has long been
      recognized to effectively induce donor-specific tolerance. Despite the
      demonstrated effectiveness of this technique, use of the mixed chimerism strategy
      in regular clinical practice has been hampered by the toxic side effects inherent
      to conventional bone marrow transplantation protocols. This Review addresses
      recent advances in preclinical and clinical studies inducing transplantation
      tolerance through mixed chimerism and discusses both the potential and the
      challenges of this approach.

PMID- 20808290
TI  - Efficacy and safety/toxicity study of recombinant vaccinia virus JX-594 in two
      immunocompetent animal models of glioma.
AB  - The purpose of this study was to investigate the oncolytic potential of the
      recombinant, granulocyte macrophage colony-stimulating factor (GM-CSF)-expressing
      vaccinia virus (VV) JX-594 in experimental malignant glioma (MGs) in vitro and in
      immunocompetent rodent models. We have found that JX-594 killed all MG cell lines
      tested in vitro. Intratumoral (i.t.) administration of JX-594 significantly
      inhibited tumor growth and prolonged survival in rats-bearing RG2 intracranial
      (i.c.) tumors and mice-bearing GL261 brain tumors. Combination therapy with JX
      594 and rapamycin significantly increased viral replication and further prolonged
      survival in both immunocompetent i.c. MG models with several animals considered
      "cured" (three out of seven rats >120 days, terminated experiment). JX-594
      infected and killed brain tumor-initiating cells (BTICs) from patient samples
      grown ex vivo, and did so more efficiently than other oncolytic viruses MYXV,
      Reovirus type-3, and VSV(DeltaM51). Additional safety/toxicity studies in
      nontumor-bearing rodents treated with a supratherapeutic dose of JX-594
      demonstrated GM-CSF-dependent inflammation and necrosis. These results suggest
      that i.c. administered JX-594 triggers a predictable GM-CSF-mediated inflammation
      in murine models. Before proceeding to clinical trials, JX-594 should be
      evaluated in the brains of nonhuman primates and optimized for the viral doses,
      delivery routes as well as the combination agents (e.g., mTOR inhibitors).

PMID- 20808289
TI  - siRNA nanoparticle functionalization of nanostructured scaffolds enables
      controlled multilineage differentiation of stem cells.
AB  - The creation of complex tissues and organs is the ultimate goal in tissue
      engineering. Engineered morphogenesis necessitates spatially controlled
      development of multiple cell types within a scaffold implant. We present a novel
      method to achieve this by adhering nanoparticles containing different small
      interfering RNAs (siRNAs) into nanostructured scaffolds. This allows spatial
      retention of the RNAs within nanopores until their cellular delivery. The
      released siRNAs were capable of gene silencing BCL2L2 and TRIB2, in mesenchymal
      stem cells (MSCs), enhancing osteogenic and adipogenic differentiation,
      respectively. This approach for enhancing a single type of differentiation is
      immediately applicable to all areas of tissue engineering. Different
      nanoparticles localized to spatially distinct locations within a single implant
      allowed two different tissue types to develop in controllable areas of an
      implant. As a consequence of this, we predict that complex tissues and organs can
      be engineered by the in situ development of multiple cell types guided by
      spatially restricted nanoparticles.

PMID- 20808292
TI  - Juvenile polyposis of the stomach--a novel cause of hypergastrinemia.
AB  - BACKGROUND: A 38-year-old female presented with a 3-year history of postprandial
      abdominal pain, refractory nausea, vomiting and hematemesis. She appeared
      malnourished and her symptoms were refractory to previous treatment with acid
      suppressive drugs, prokinetics and antiemetics. Her medical history was
      significant for a diagnosis of juvenile polyposis syndrome at the age of 14
      resulting in a transverse colectomy, and a diagnosis of Crohn's disease in her
      residual colon at the age of 35 resulting in a total colectomy. INVESTIGATIONS:
      Physical examination, blood analysis, esophagogastroduodenoscopy with biopsy,
      abdominal endoscopic ultrasound, abdominal CT scan, MRI, 24 h urine analysis,
      MIBG scintigraphy, ocreotide scintigraphy, fluorodeoxyglucose-PET scan and
      genetic testing for defined polyposis syndromes (SMAD4, BMPR1A). DIAGNOSIS:
      Juvenile polyposis syndrome with outlet obstruction of the stomach and excessive
      hypergastrinemia. MANAGEMENT: Continuous acid-suppressive therapy, prokinetic
      therapy and total parenteral nutrition. Repetitive endoscopic polypectomy (also
      known as debulking) was performed twice and was followed by gastrectomy with
      duodenoesophageal anastomosis.

PMID- 20808291
TI  - Adenovirus-retrovirus hybrid vectors achieve highly enhanced tumor transduction
      and antitumor efficacy in vivo.
AB  - Murine leukemia virus (MLV)-based replication-competent retrovirus (RCR) vectors
      have been shown to mediate efficient, selective, and persistent tumor
      transduction, thereby achieving significant therapeutic benefit in a wide variety
      of cancer models. To further augment the efficiency of this strategy, we have
      developed a delivery method employing a gutted adenovirus encoding an RCR vector
      (AdRCR); thus, tumor cells transduced with the adenoviral vector transiently
      become RCR vector producer cells in situ. As expected, high-titer AdRCR achieved
      significantly higher initial transduction levels in human cancer cells both in
      vitro and in vivo, as compared to the original RCR vector itself. Notably, even
      at equivalent initial transduction levels, more secondary RCR progeny were
      produced from AdRCR-transduced cells as compared to RCR-transduced cells,
      resulting in further acceleration of subsequent RCR replication kinetics. In pre
      established tumor models in vivo, prodrug activator gene therapy with high-titer
      AdRCR could achieve enhanced efficacy compared to RCR alone, in a dose-dependent
      manner. Thus, AdRCR hybrid vectors offer the advantages of high production titers
      characteristic of adenovirus and secondary production of RCR in situ, which not
      only accelerates subsequent vector spread and progressive tumor transduction, but
      can also significantly enhance the therapeutic efficacy of RCR-mediated prodrug
      activator gene therapy.

PMID- 20808293
TI  - Hepatotoxic effects of therapies for tuberculosis.
AB  - Hepatotoxic effects attributable to antituberculosis therapy are considered
      unique among drug-related liver problems because almost all first-line
      antituberculosis medications have such adverse effects, which vary in severity
      according to the drug and the regimen. In addition, all regimens for the
      treatment of active tuberculosis include a combination of medications that must
      typically be administered for at least 6 months to ensure complete cure of the
      disease and to minimize the development of drug-resistant bacterial strains.
      Hepatotoxic effects are a serious problem in patients who are undergoing
      treatment for tuberculosis, not only because of the morbidity and mortality they
      directly cause, but also because the liver symptoms can necessitate interruption
      of therapy or affect a patient's adherence to it, which can limit the efficacy of
      the antitubercular regimen.

PMID- 20808294
TI  - The safety profile of biologic therapies for juvenile idiopathic arthritis.
AB  - The treatment of juvenile idiopathic arthritis (JIA) has been revolutionized by
      the use of novel biologic agents that have much improved patients' short-term
      and, according to early evidence, long-term outcomes. Currently available
      biologic agents used to treat patients with JIA include tumor necrosis factor
      (TNF) blockers, various agents that target interleukin (IL)-1 and the IL-6
      receptor, T-cell co-stimulation inhibitors and antibodies to B-lymphocyte antigen
      CD20. These agents are increasingly used early in the course of the disease
      (often in combination with other immunosuppressive medications) and often for
      long periods of time, as patients can be difficult to wean from their use. Safety
      concerns (especially the long-term effects of biologic therapy) are, therefore,
      being examined more closely. For instance, in 2009, the FDA issued a warning
      related to the development of malignancies in patients with JIA who had used anti
      TNF medications for >2.5 years. In this Review, data related to the safety
      profile of all currently available biologic agents used to treat JIA are
      examined, with a particular focus on anti-TNF therapy, the most studied biologic
      agent for JIA. Safety issues that need further study, including the
      implementation of registries to monitor long-term drug safety, are also
      discussed.

PMID- 20808296
TI  - How reliable are the Rome III criteria for the assessment of functional
      gastrointestinal disorders in children?
AB  - OBJECTIVES: Functional gastrointestinal disorders (FGIDs) are common in children.
      Diagnosis of these conditions is based on the pediatric Rome criteria. In the
      past, we have shown that there was low inter-rater reliability (IRR) among
      pediatric gastroenterologists using the Rome II criteria. Since then, a new
      version of the criteria has been issued. The reliability of the Rome III criteria
      has not been established. METHODS: A total of 10 pediatric gastroenterologist
      specialists and 10 pediatric gastroenterology fellows were provided with 20
      clinical vignettes and a list of 17 possible diagnoses (all pediatric categories
      of the Rome criteria plus "none of the above" or "not enough information") and
      instructed to select one or more diagnosis for each vignette. RESULTS: The
      average percentage of agreement among the raters was 50% for the pediatric
      gastroenterologists and 45% for the pediatric gastroenterology fellows. The inter
      rater percentage of agreement per clinical case was >50% in only 7 out of 20
      (35%) vignettes for the gastroenterologists and only 6 out of 20 (30%) cases for
      the fellows. The inter-rater percentage of agreement was <25% in 2 out of 20
      (10%) vignettes for the gastroenterologists and 4 out of 20 (20%) vignettes for
      the fellows. The kappa coefficient was 0.45 for the specialists (P<0.0001) and
      0.39 for the fellows (P<0.0001). In a subanalysis of the groups of pain and
      constipation-related disorders, the inter-rater percentage of agreement per
      clinical case ranged between 27 and 100% (mean 57%, kappa=0.37, P<0.0001) for the
      gastroenterologists and between 36 and 80% (mean 52%, kappa=0.33, P<0.0001) for
      the fellows in the constipation subgroup. The inter-rater percentage of agreement
      per clinical case for the pain subgroup ranged between 22 and 80% (mean 48%,
      kappa=0.36, P<0.0001) for the gastroenterologists and 22 and 62% (mean 39%,
      kappa=0.29, P<0.0001) for the fellows in the pain subgroup. The kappa coefficient
      for specialists with expertise in FGIDs was 0.37 (P<0.0001) and for those with
      expertise in other gastroenterology conditions was 0.53 (P<0.0001). CONCLUSIONS:
      The IRR among pediatric gastroenterologists and fellows was found to be fair to
      moderate for the Rome III criteria. Only slight to fair agreement between raters
      existed for important subcategories of pain and constipation. The results from
      our current study are almost similar to that of the IRR study done for the Rome
      II criteria. This indicates the need for further refinement of the Rome criteria
      to make them more encompassing and user friendly.

PMID- 20808295
TI  - The yin and yang of regulatory T cells and inflammation in RA.
AB  - Rheumatoid arthritis (RA) is characterized by chronic inflammation leading to
      joint destruction. Regulatory T (T(REG)) cells are potent suppressors of
      autoimmunity, but are not capable of controlling every aspect of the inflammatory
      reaction. We have found that T(REG)-cell function is abnormal in patients with
      RA, and that a distinct population of T(REG) cells with potent suppressive
      properties is induced after therapy with inhibitors of tumor necrosis factor. In
      this Review, we discuss the mutual interactions between the opposing forces of
      T(REG) cells and inflammation in the context of RA. Therapeutic approaches that
      enhance T(REG)-cell function whilst controlling inflammation are likely to be the
      most effective strategies for restoring immune tolerance in patients with this
      disease.

PMID- 20808297
TI  - Frequency and risk factors for extraintestinal manifestations in the Swiss
      inflammatory bowel disease cohort.
AB  - OBJECTIVES: Data on the frequency of extraintestinal manifestations (EIMs) in
      Crohn's disease (CD) and ulcerative colitis (UC) and analyses of their risk
      factors are scarce. We evaluated their prevalence and risk factors in a large
      nationwide cohort of inflammatory bowel disease (IBD) patients. METHODS: IBD
      patients from an adult clinical cohort in Switzerland (Swiss IBD cohort study)
      were prospectively included. Data from validated physician enrolment
      questionnaires were analyzed. RESULTS: A total of 950 patients were included, 580
      (61%) with CD (mean age 41 years) and 370 (39%) with UC (mean age 42 years). Of
      these, 249 (43%) of CD and 113 (31%) of UC patients had one to five EIMs. The
      following EIMs were found: arthritis (CD 33%, UC 21%), aphthous stomatitis (CD
      10%, UC 4%), uveitis (CD 6%, UC 4%), erythema nodosum (CD 6%, UC 3%), ankylosing
      spondylitis (CD 6%, UC 2%), psoriasis (CD 2%, UC 1%), pyoderma gangrenosum (CD
      and UC each 2%), and primary sclerosing cholangitis (CD 1%, UC 4%). Multiple
      logistic regression identified the following risk factors for ongoing EIM in CD:
      active disease (odds ratio (OR)=1.95, 95% confidence interval (CI)=1.17-3.23,
      P=0.01), and positive IBD family history (OR=1.77, 95% CI=1.07-2.92, P=0.025). No
      risk factors were identified in UC patients. CONCLUSIONS: EIMs are a frequent
      problem in CD and UC patients. Active disease and positive IBD family history are
      associated with ongoing EIM in CD patients. Identification of EIM prevalence and
      associated risk factors may result in increased awareness for this problem and
      thereby facilitating their diagnosis and therapeutic management.

PMID- 20808298
TI  - Non-steroidal anti-inflammatory drug use and colorectal polyps in the Prostate,
      Lung, Colorectal, And Ovarian Cancer Screening Trial.
AB  - OBJECTIVES: Non-steroidal anti-inflammatory drugs (NSAIDs) have been documented
      in animal and human studies to reduce risk for colorectal cancer and adenomatous
      polyps, but risk modification for subgroups of the population and effects on
      hyperplastic polyps have been less studied. METHODS: Data on recent use of two
      frequently ingested NSAIDs, aspirin and ibuprofen, were collected at baseline
      from participants aged 55-74 years in the 10 centers of the Prostate, Lung,
      Colorectal, and Ovarian Cancer Screening Trial (PLCO). Participants randomized to
      the intervention arm of the trial received a flexible sigmoidoscopy during a
      baseline examination. Follow-up of detected polyps was accomplished outside the
      Trial setting and relevant records were sought and abstracted. Cases (n=4,017)
      included subjects with a biopsy-proven polyp in the left side of the colon
      (descending colon, sigmoid, and rectum) detected as a consequence of PLCO
      screening; controls (n=38,396) were subjects with no left-sided colon polyp.
      RESULTS: Regular use of aspirin (>= 4 times/month) in the past year was inversely
      associated with hyperplastic polyps (odds ratios (OR)=0.8, 95% confidence
      interval (CI)=0.7-0.9), adenomatous polyps (OR=0.8, 95% CI=0.8-0.9), and advanced
      adenomas (OR=0.8, 95% CI=0.7-0.9). As frequency of aspirin use increased, the
      prevalence of polyps decreased significantly for each histological classification
      (P for trend <= 0.0004). Similar patterns were found for adenomas and ibuprofen.
      Overall protection was consistent in both the descending colon or sigmoid and the
      rectum, but more evident in males. In males, the OR for heavy use of combined
      aspirin and ibuprofen (>= 2 times/day) was 0.6 (95% CI=0.5-0.8), as opposed to
      0.9 (95% CI=0.8-1.1) in females. The protective effects of NSAIDs for females
      were apparent only among those with body mass index (BMI) <25 (OR=0.8, 95% CI=0.7
      1.0 for regular use of NSAIDs; P interaction=0.04). We also found a slightly
      stronger protection of NSAIDs in the 70-74 years age group compared with those
      aged 55-69 years. CONCLUSIONS: This study of a large general risk population
      supports previous work that recent use of aspirin and ibuprofen is associated
      with a decreased risk of colorectal adenomas and demonstrates that this
      protective effect may be stronger in certain population subgroups and is also
      evident for aspirin and hyperplastic polyps.

PMID- 20808299
TI  - The role of radiotherapy for metastatic epidural spinal cord compression.
AB  - Radiotherapy alone is the most common treatment for metastatic epidural spinal
      cord compression (MESCC). Decompressive surgery followed by radiotherapy is
      generally indicated only in 10-15% of MESCC cases. Chemotherapy has an unclear
      role and may be considered for selected patients with hematological or germ-cell
      malignancies. If radiotherapy alone is given, it is important to select the
      appropriate regimen. Similar functional outcomes can be achieved with short
      course radiotherapy regimens and longer-course radiotherapy regimens. Longer
      course radiotherapy is associated with better local control of MESCC than short
      course radiotherapy. Patients with a more favorable survival prognosis (expected
      survival of >=6 months) should receive longer-course radiotherapy, as they may
      live long enough to develop a recurrence of MESCC. Patients with an expected
      survival of <6 months should be considered for short-course radiotherapy. A
      recurrence of MESCC in the previously irradiated region after short-course
      radiotherapy may be treated with another short-course of radiotherapy. After
      primary administration of longer-course radiotherapy, decompressive surgery
      should be performed if indicated. Alternatively, re-irradiation can be performed
      using high-precision techniques to reduce the cumulative dose received by the
      spinal cord. Larger prospective trials are required to better define the
      appropriate treatment for the individual patient.

PMID- 20808300
TI  - Rechallenging with anthracyclines and taxanes in metastatic breast cancer.
AB  - Adjuvant use of anthracycline-taxane combination therapy is an accepted strategy
      in the management of high-risk early-stage breast cancer. However, the
      introduction of this regimen raises the question of how best to manage those
      patients who relapse following adjuvant therapy, and whether there is a role for
      rechallenging in the metastatic setting with the same agent, or class of agent,
      that has been utilized in the adjuvant setting. This Review examines the evidence
      for rechallenging with both anthracyclines and taxanes, and highlights the issues
      that need to be examined in the context of future clinical trials.

PMID- 20808301
TI  - Complete molecular response in CML after p210 BCR-ABL1-derived peptide
      vaccination.
AB  - BACKGROUND: A 63-year-old woman with chronic myeloid leukemia (CML) received
      treatment with interferon (IFN)-alpha for 6 years. After achieving a complete
      cytogenetic response that was repetitively documented, IFN-alpha treatment was
      stopped. Despite maintenance of a complete cytogenetic response, a progressive
      rise of the BCR-ABL1 transcript was detected and loss of major molecular response
      occurred about 2 years after stopping IFN-alpha therapy. Disease remained at
      molecular level. INVESTIGATIONS: Peripheral blood quantitative real-time PCR
      every 3 months and periodical bone marrow aspirate were performed to monitor
      disease. DIAGNOSIS: Chronic-phase, Philadelphia-positive CML that was still
      detectable after complete cytogenic response 2 years after cessation of IFN-alpha
      therapy. MANAGEMENT: The patient was treated with a target immune approach
      receiving a therapeutic vaccine that consisted of an immunogenic 25-mer b2a2
      breakpoint-derived peptide (CMLb2a2-25) with binding properties for several HLA
      DR molecules. After nine boosts of vaccine the patient developed an adequate b2a2
      25 peptide-specific CD4(+) T-cell response and BCR-ABL1 transcript started to
      decline in peripheral blood. No hematological or extrahematological effects were
      documented during therapy. At the last evaluation, 39 months since vaccinations
      commenced, the patient is in complete molecular response with an undetectable
      level of BCR-ABL1 transcript both in peripheral blood and in bone marrow and she
      continues to receive boosts of vaccine every 3 months as the only treatment.

PMID- 20808303
TI  - Fibromyalgia: Increased regular physical activity as 'exercise' in fibromyalgia.

PMID- 20808304
TI  - Psoriasis: Is ustekinumab superior to etanercept for psoriasis?

PMID- 20808305
TI  - Bone: Do all Paget disease risk genes incriminate the osteoclast?

PMID- 20808302
TI  - Future directions of bone-targeted therapy for metastatic breast cancer.
AB  - Bone is the most common metastatic site for breast cancer, and bone metastases
      can cause pain as well as risk of pathological fractures. Emerging treatments for
      metastatic bone disease have arisen from advances in our understanding of the
      unique cellular and molecular mechanisms that contribute to bone metastasis. The
      interaction between tumor cells and the bone microenvironment results in a
      'vicious cycle' that increases both bone destruction and tumor burden. The tumor
      secretes factors, such as parathyroid hormone-related peptide, that stimulate
      osteoclastogenesis. Similarly, the bone stroma produces growth factors, such as
      transforming growth factor beta, that promote tumor growth in bone. Therapeutic
      targeting of these microenvironmental factors is under intensive investigation.
      Other attractive therapeutic targets include signaling molecules, such as
      receptor activator of nuclear factor kappaB ligand, Src kinase, and cathepsin K,
      all of which regulate osteoclast function, and chemokine receptor 4, which is
      involved in the homing of tumor cells to bone. In this Review, we describe the
      progress and future directions of novel bone-targeted therapies that may reduce
      or prevent destructive bone metastasis from breast cancer. Novel modalities for
      predicting and monitoring treatment response will also be described.

PMID- 20808306
TI  - Connective tissue diseases: Translating the effects of BAFF in SLE.

PMID- 20808307
TI  - Rheumatoid arthritis: Guidelines for RA therapy-avoiding hamartia.

PMID- 20808308
TI  - Prognostic significance of AMP-activated protein kinase expression and modifying
      effect of MAPK3/1 in colorectal cancer.
AB  - BACKGROUND: AMP-activated protein kinase (AMPK, PRKA) has central roles in
      cellular metabolic sensing and energy balance homeostasis, and interacts with
      various pathways (e.g., TP53 (p53), FASN, MTOR and MAPK3/1 (ERK)). AMP-activated
      protein kinase activation is cytotoxic to cancer cells, supporting AMPK as a
      tumour suppressor and a potential therapeutic target. However, no study has
      examined its prognostic role in colorectal cancers. METHODS: Among 718 colon and
      rectal cancers, phosphorylated AMPK (p-AMPK) and p-MAPK3/1 expression was
      detected in 409 and 202 tumours, respectively, by immunohistochemistry. Cox
      proportional hazards model was used to compute mortality hazard ratio (HR),
      adjusting for clinical and tumoral features, including microsatellite
      instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF
      and PIK3CA mutations. RESULTS: Phosphorylated AMPK expression was not associated
      with survival among all patients. Notably, prognostic effect of p-AMPK
      significantly differed by p-MAPK3/1 status (P(interaction)=0.0017).
      Phosphorylated AMPK expression was associated with superior colorectal cancer
      specific survival (adjusted HR 0.42; 95% confidence interval (CI), 0.24-0.74)
      among p-MAPK3/1-positive cases, but not among p-MAPK3/1-negative cases (adjusted
      HR 1.22; 95% CI: 0.85-1.75). CONCLUSION: Phosphorylated AMPK expression in
      colorectal cancer is associated with superior prognosis among p-MAPK3/1-positive
      cases, but not among p-MAPK3/1-negative cases, suggesting a possible interaction
      between the AMPK and MAPK pathways influencing tumour behaviour.

PMID- 20808310
TI  - Comparison of Hybrid capture 2 testing at different thresholds with cytology as
      primary cervical screening test.
AB  - BACKGROUND: We evaluated the performance of primary high-risk human
      papillomavirus (hrHPV) testing by hybrid capture 2 (HC2) with different
      thresholds for positivity, in comparison with conventional cytology. METHODS: We
      used data of 25,871 women (aged 30-60 years) from the intervention group of the
      VUSA-Screen study (VU University Medical Center and Saltro laboratory population
      based cervical screening study), who were screened by cytology and hrHPV. Primary
      outcome measure was the number of cervical intraepithelial neoplasia grade 3 or
      higher (CIN3+), detected within 3 years. We compared baseline cytology testing
      with three possible hrHPV screening strategies at different relative light
      unit/cutoff (RLU/CO) thresholds. RESULTS: Compared with baseline cytology
      testing, hrHPV DNA testing as a sole primary screening instrument did not yield a
      superior sensitivity, as well as lower colposcopy referral rate and lower false
      positivity rate at any RLU/CO threshold. The hrHPV screening at 1 RLU/CO
      threshold with cytology triage at baseline and at 12 months revealed the highest
      sensitivity for CIN3+ (relative sensitivity of 1.32), although still displaying a
      lower colposcopy referral rate than cytology testing (relative colposcopy rate of
      0.94). Higher thresholds (>1 RLU/CO) yielded lower colposcopy rates, but resulted
      in substantial loss in sensitivity. CONCLUSIONS: The hrHPV testing at the
      commonly used threshold of 1 RLU/CO with cytology triage at baseline and at 12
      months showed a much higher sensitivity with a lower colposcopy referral rate
      compared with cytology testing.

PMID- 20808311
TI  - A clinical risk score to predict 3-, 5- and 10-year survival in patients
      undergoing surgery for Dukes B colorectal cancer.
AB  - BACKGROUND: The prognosis of patients with Dukes stage B colorectal cancer is
      unpredictable and there is continuing interest in simply and reliably identifying
      patients at high risk of developing recurrence and dying of their disease. The
      aim of this study was to devise a clinical risk score to predict 3-, 5- and 10
      year survival in patients undergoing surgery for Dukes stage B colorectal cancer.
      METHODS: A total of 1350 patients who underwent surgery for Dukes stage B
      colorectal cancer between 1991 and 1994 in 11 hospitals in Scotland were included
      in the analysis. RESULTS: On follow-up, 926 patients died of whom 479 died of
      their cancer. At 10 years, cancer-specific survival was 61% and overall survival
      was 38%. On multivariate analysis, age >=75 (hazard ratio (HR) 1.45, 95%
      confidence interval (CI) 1.15-1.82, P=0.001), emergency presentation (HR 1.59,
      95% CI 1.27-1.99, P<0.001) and anastomotic leak (HR 2.17, 95% CI 1.24-3.78,
      P<0.01) were independently associated with cancer-specific survival in colon
      cancer. On multivariate analysis, only age >=75 (HR 1.58, 95% CI 1.14-2.18,
      P<0.01) was associated with cancer-specific survival in rectal cancer. Age,
      presentation and anastomotic leak hazards could be simply added to form a
      clinical risk score from 0 to 2 in colon cancer. In patients with Dukes B stage
      colon cancer, the cancer-specific survival at 5 years for patients with a
      cumulative score 0 was 81%, 1 was 67% and 2 was 63%. The cancer-specific survival
      rate at 10 years for patients with a clinical risk score of 0 was 72%, 1 was 58%
      and 2 was 53%. CONCLUSION: The results of this study, in a mature cohort,
      introduce a new simple clinical risk score for patients undergoing surgery for
      Dukes B colon cancer. This provides a solid foundation for the examination of the
      impact of additional factors and treatment on prediction of 3-, 5- and 10-year
      cancer-specific survival.

PMID- 20808309
TI  - A randomised phase II study of pegylated arginine deiminase (ADI-PEG 20) in Asian
      advanced hepatocellular carcinoma patients.
AB  - BACKGROUND: Human hepatocellular carcinoma (HCC) cells are largely deficient of
      argininosuccinate synthetase and thus auxotrophic for arginine. This study aims
      to investigate the efficacy and pharmacodynamics of pegylated arginine deiminase
      (ADI-PEG 20), a systemic arginine deprivation agent, in Asian HCC patients.
      METHODS: Patients with advanced HCC who were not candidates for local therapy
      were eligible and randomly assigned to receive weekly intramuscular injections of
      ADI-PEG 20 at doses of 160 or 320 IU m(-2). The primary end point was disease
      control rate (DCR). RESULTS: Of the 71 accruals, 43.6% had failed previous
      systemic treatment. There were no objective responders. The DCR and the median
      overall survival (OS) of the intent-to-treat population were 31.0% (95%
      confidence interval (CI): 20.5-43.1) and 7.3 (95% CI: 4.7-9.9) months
      respectively. Both efficacy parameters were comparable between the two study
      arms. The median OS of patients with undetectable circulating arginine for more
      than or equal to and <4 weeks was 10.0 (95% CI: 2.1-17.9) and 5.8 (95% CI: 1.4
      10.1) months respectively (P=0.251, log-rank test). The major treatment-related
      adverse events were grades 1-2 local and/or allergic reactions. CONCLUSIONS: ADI
      PEG 20 is safe and efficacious in stabilising the progression of heavily
      pretreated advanced HCC in an Asian population, and deserves further exploration.

PMID- 20808312
TI  - Ubiquitin D is correlated with colon cancer progression and predicts recurrence
      for stage II-III disease after curative surgery.
AB  - BACKGROUND: Our recent study observed that the expression of ubiquitin D (UBD), a
      member of ubiquitin-like modifier family, was upregulated in colon cancer
      parenchymal cells. The present study further investigated the clinical signicance
      of UBD in colon cancer. METHODS: Using quantitative PCR, tissue microarray (TMA),
      western blot analysis and immunohistochemical stain, we evaluated UBD mRNA and
      protein levels in tumour tissues from patients with colon cancer at different
      stages and in paired adjacent normal epithelium. RESULTS: Immunohistochemical
      detection of UBD on a TMA containing 203 paired specimens showed that increased
      cytoplasmic UBD was signicantly associated with depth of cancer invasion, lymph
      node metastasis, distant metastasis, tumour histologic grade, advanced clinical
      stage and Ki-67 proliferative index. Patients with UBD-positive tumours had a
      significantly higher disease recurrence rate and poorer survival than patients
      with UBD-negative tumours after the radical surgery. Stratification analysis
      according to tumour stage revealed UBD as an independent predictor for tumour
      recurrence in patients with stage II and III tumours. CONCLUSION: UBD may
      contribute to the progression of colon carcinogenesis and function as a novel
      prognostic indicator of forecasting recurrence of stage II and III patients after
      curative operations.

PMID- 20808313
TI  - Thyroid cancer following nuclear tests in French Polynesia.
AB  - BACKGROUND: Between 1966 and 1974, France conducted 41 atmospheric nuclear tests
      in Polynesia, but their potential health effects have not previously been
      investigated. METHODS: In a case-control study, we compared the radiation
      exposure of almost all the French Polynesians diagnosed with differentiated
      thyroid carcinoma between 1981 and 2003 (n=229) to the exposure of 373 French
      Polynesian control individuals without cancer from the general population.
      Radiation exposures were estimated using measurements after the nuclear tests,
      age at time of each test, residential and dietary information. RESULTS: The
      average thyroid dose before 15 years of age was about 1.8 mGy, and 5% of the
      cases and 3% of the controls received a dose above 10 mGy. Despite this low level
      of dose, and after adjusting for ethnic group, level of education, body surface
      area, family history of thyroid cancer and number of pregnancies for women, we
      observed an increasing risk (P=0.04) of thyroid cancer with increasing thyroid
      dose received before age of 15 years, which remained after excluding non
      aggressive differentiated thyroid micro-carcinomas. This increase of risk per
      unit of thyroid radiation dose was higher (P=0.03) in women who later experienced
      four or more pregnancies than among other women. CONCLUSION: The risk estimate is
      low, but is based on limited exposure data. The release of information on
      exposure, currently classified, would greatly improve the reliability of the risk
      estimation.

PMID- 20808314
TI  - A phase I/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal
      antibody, in metastatic renal cell cancer.
AB  - BACKGROUND: Serum interleukin (IL)-6 levels correlate with disease outcomes in
      renal cell carcinoma (RCC) patients. Siltuximab, a chimeric, murine-human mAb
      against IL-6, was evaluated in a three-part phase I/II study in patients with
      progressive metastatic RCC. METHODS: In part 1, 11 patients received 1, 3, 6, or
      12mgkg-1 at weeks 1, 4 and q2w * 2 thereafter; in part 2, 37 patients randomly
      received 3 or 6 mgkg-1 q3w * 4; in part 3, 20 low-risk patients received 6mgkg-1
      q2w * 6. Modified WHO response criteria were assessed at weeks 7, 11, the 6-week
      follow-up, and when clinically indicated. RESULTS: Siltuximab was well tolerated
      overall, with no maximum tolerated dose or immune response observed. In all, 5
      out of 11, 17 out of 37, and 9 out of 20 patients in parts 1, 2, and 3,
      respectively, received extended treatment beyond 4-6 initial infusions. In part
      2, stable disease (SD) (>=11weeks) or better was achieved by 11 out of 17 (65%) 3
      mgkg-1 treated patients (one partial response (PR) ~8 months, 10 SD) and 10 out
      of 20 (50%) 6mgkg-1 treated patients (10 SD). In part 3, documented complete or
      PR was not observed, but 13 out of 20 (65%) patients achieved SD. CONCLUSION:
      Siltuximab stabilised disease in >50% of progressive metastatic RCC patients. One
      PR was observed. Given the favourable safety profile of siltuximab and poor
      correlation of tumour shrinkage with clinical benefit demonstrated for other non
      cytotoxic therapies, further evaluation of dose-escalation strategies and/or
      combination therapy may be considered for patients with RCC.

PMID- 20808315
TI  - The herbicide ketoclomazone inhibits 1-deoxy-D-xylulose 5-phosphate synthase in
      the 2-C-methyl-D-erythritol 4-phosphate pathway and shows antibacterial activity
      against Haemophilus influenzae.
AB  - Two distinct metabolic pathways have been elucidated for the formation of
      isopentenyl diphosphate and dimethylallyl diphosphate, essential metabolic
      precursors for isoprenoid biosynthesis: the mevalonate pathway, found
      ubiquitously in mammals, and the 2-C-methyl-D-erythritol 4-phosphate (MEP)
      pathway, found in most bacteria. As the MEP pathway is absent from mammals, all
      MEP pathway enzymes represent effective targets for the development of
      antibacterial drugs. In this study, we found that a herbicide, ketoclomazone,
      exhibited antibacterial activity against a pathogenic bacterium, Haemophilus
      influenzae, with an MIC value of 12.5 MUg  ml(-1) and that antibacterial activity
      was suppressed by adding 1-deoxyxylulose, a free alcohol of 1-deoxy-D-xylulose 5
      phosphate (DXP). DXP is an MEP pathway intermediate synthesized from pyruvate and
      D-glyceraldehyde 3-phosphate (D-GAP) by the action of DXP synthase. Thus, we
      investigated the enzyme kinetics of DXP synthase of H. influenzae (HiDXS) to
      elucidate an inhibitory mechanism of ketoclomazone on HiDXS. The dxs gene was
      cloned from H. influenzae and overexpressed in Escherichia coli, and the enzyme
      was purified to homogeneity. The purified HiDXS was a soluble dimeric 70-kDa
      protein. Steady-state kinetic constants for HiDXS were calculated, and Lineweaver
      Burk plots were consistent with a ping-pong bi bi mechanism. The kinetics of
      inhibition by ketoclomazone suggested that ketoclomazone binds to an unidentified
      inhibitor-binding site that differs from both the pyruvate-binding site and the D
      GAP-binding site on DXP synthase. These data reveal the inhibitory mechanism of
      ketoclomazone on DXP synthase.

PMID- 20808316
TI  - A new 16-membered tetraene macrolide JBIR-100 from a newly identified
      Streptomyces species.

PMID- 20808317
TI  - The FAQ initiative explaining pathology reports to patients.

PMID- 20808318
TI  - The use of alternative forms of graphical analysis to balance bias and precision
      in PET images.
AB  - Graphical analysis (GA) is an efficient method for estimating total tissue
      distribution volume (V(T)) from positron emission tomography (PET) uptake data.
      The original GA produces a negative bias in V(T) in the presence of noise.
      Estimates of V(T) using other GA forms have less bias but less precision. Here,
      we show how the bias terms are related between the GA methods and how using an
      instrumental variable (IV) can also reduce bias. Results are based on simulations
      of a two-compartment model with V(T)'s ranging from 10.5 to 64 mL/cm(3) and from
      PET image data with the tracer [(11)C]DASB ([(11)C]-3-amino-4-(2
      dimethylaminomethyl-phenylsulfanyl) benzonitrile). Four estimates of V(T) (or
      distribution volume ratio (DVR) using a reference tissue) can be easily computed
      from different formulations of GA including the IV. As noise affects the
      estimates from all four differently, they generally do not provide the same
      estimates. By taking the median value of the four estimates, we can decrease the
      bias and reduce the effect of large values contributing to noisy images. The
      variance of the four estimates can serve as a guide to the reliability of the
      median estimate. This may provide a general method for the generation of
      parametric images with little bias and good precision.

PMID- 20808319
TI  - Cumulative input function method for linear compartmental models and spectral
      analysis in PET.
AB  - Compartmental modeling and spectral analysis are often used for tracer kinetic
      modeling in positron emission tomography (PET). The concentrations in kinetic
      equations are usually considered to be instantaneous, whereas PET data are
      inherently integrated over time, which leads to uncertainties in the results. A
      new formalism for kinetic analysis that uses cumulative tracer concentrations and
      avoids approximating the image-derived input function and PET measurements with
      midframe instantanous values was developed. We assessed the improvements of the
      new formalism over the midframe approximation methods for three commonly used
      radiopharmaceuticals: [(11)C]raclopride, 2'-deoxy-2'-[(18)F]fluoro-D-glucose
      (FDG), and 3'-deoxy-3'-[(18)F]fluoro-thymidine (FLT). We found that improvements
      are case dependent and often not negligible. Improvements for determination of
      binding potential for [(11)C]raclopride ranged from 5% to 25%. Improvements in
      estimation accuracy of FDG and FLT microparameters ranged up to 25%. On the other
      hand, estimation of macroparameter K(i)=K(1)k(3)/(k(2)+k(3)) for FDG or FLT did
      not show significant benefit with the new method; only modest improvement up to
      2% was observed. Assessment of the benefits of using new method is far from being
      exhaustive, but possibly significant improvement was demonstrated. Therefore, we
      consider the proposed algorithm a necessary component of any kinetic analysis
      software.

PMID- 20808320
TI  - Gene therapy and bone marrow transplantation for thalassemia: changing of the
      guard?

PMID- 20808323
TI  - Breathing new life into lung transplantation therapy.

PMID- 20808324
TI  - Genetic determination of male sterility in gynodioecious Silene nutans.
AB  - Gynodioecy, the coexistence of female and hermaphrodite plants within a species,
      is often under nuclear-cytoplasmic sex determination, involving cytoplasmic male
      sterility (CMS) genes and nuclear restorers. A good knowledge of CMS and restorer
      polymorphism is essential for understanding the evolution and maintenance of
      gynodioecy, but reciprocal crossing studies remain scarce. Although mitochondrial
      diversity has been studied in a few gynodioecious species, the relationship
      between mitotype diversity and CMS status is poorly known. From a French sample
      of Silene nutans, a gynodioecious species whose sex determination remains
      unknown, we chose the four most divergent mitotypes that we had sampled at the
      cytochrome b gene and tested by reciprocal crosses whether they carry distinct
      CMS genes. We show that gynodioecy in S. nutans is under nuclear-cytoplasmic
      control, with at least two different CMSs and up to four restorers with epistatic
      interactions. Female occurrence and frequency were highly dependent on the
      mitotype, suggesting that the level of restoration varies greatly among CMSs. Two
      of the mitotypes, which have broad geographic distributions, represent different
      CMSs and are very unequally restored. We discuss the dynamics of gynodioecy at
      the large-scale meta-population level.

PMID- 20808325
TI  - Duplication of MAOA, MAOB, and NDP in a patient with mental retardation and
      epilepsy.

PMID- 20808327
TI  - Role of physical activity and diet in incidence of hypertension: a population
      based study in Portuguese adults.
AB  - BACKGROUND/OBJECTIVES: To evaluate longitudinally the role of physical activity
      (PA) (type and intensity) and diet (measured using DASH score, nutrients and food
      intake) in hypertension incidence. SUBJECTS/METHODS: As part of the EPIPorto
      study, 549 participants (>=40 years), resident in Porto, Portugal, at risk of
      developing hypertension, were evaluated. Blood pressure (BP) measurements were
      obtained twice (1999-2003 and 2005-2008), with a median interval of 3.8 years.
      Hypertension was defined as systolic BP >=140 mm Hg and/or diastolic BP >=90 mm
      Hg, and/or if the subjects were under anti-hypertensive therapy. Validated
      questionnaires were used to assess usual PA and dietary intake during the
      previous year. Poisson regression was used to calculate the incident rate ratios
      (IRRs) and respective 95% confidence intervals (95% CIs). RESULTS: In our
      population, the crude incidence rate (95% confidence interval (CI)) per 100
      person-years of hypertension was 6.23 (5.26-7.20). After adjustment for several
      confounders, an inverse, though not significant, association was found across
      increasing tertiles of leisure-time PA and IRR (95% CI): 1 (reference); 0.77
      (0.51-1.16); and 0.74 (0.48-1.11). No significant associations between the DASH
      score and hypertension incidence were observed. However, potassium intake
      (mg/1000 kcal) was shown to be inversely associated with hypertension development
      (upper tertile: >1863.0 for women and >1657.2 for men) vs first tertile (IRR=0.65
      (0.44-0.96), P for trend=0.025). Additionally, in multivariate analysis, a
      significantly inverse association between the consumption of
      fruits/vegetables/pulses and hypertension incidence was found (upper vs first
      tertile: IRR=0.61 (0.40-0.93), P for trend=0.024). CONCLUSIONS: In Portuguese
      adults, after adjustment for several confounders, the development of hypertension
      was inversely associated with potassium and fruits/vegetables/pulses intake. A
      dose-response is inherent to these inverse associations.

PMID- 20808326
TI  - Genome-wide association study with DNA pooling identifies variants at CNTNAP2
      associated with pseudoexfoliation syndrome.
AB  - Genetic and nongenetic factors contribute to development of pseudoexfoliation
      (PEX) syndrome, a complex, age-related, generalized matrix process frequently
      associated with glaucoma. To identify specific genetic variants underlying its
      etiology, we performed a genome-wide association study (GWAS) using a DNA-pooling
      approach. Therefore, equimolar amounts of DNA samples of 80 subjects with PEX
      syndrome, 80 with PEX glaucoma (PEXG) and 80 controls were combined into separate
      pools and hybridized to 500K SNP arrays (Affymetrix). Array probe intensity data
      were analyzed and visualized with expressly developed software tools GPFrontend
      and GPGraphics in combination with GenePool software. For replication,
      independent German cohorts of 610 unrelated patients with PEX/PEXG and 364
      controls as well as Italian cohorts of 249 patients and 190 controls were used.
      Of 19, 17 SNPs showing significant allele frequency difference in DNA pools were
      confirmed by individual genotyping. Further single genotyping at CNTNAP2 locus
      revealed association between PEX/PEXG for two SNPs, which was confirmed in an
      independent German but not the Italian cohort. Both SNPs remained significant in
      the combined German cohorts even after Bonferroni correction (rs2107856:
      P(c)=0.0108, rs2141388: P(c)=0.0072). CNTNAP2 was found to be ubiquitously
      expressed in all human ocular tissues, particularly in retina, and localized to
      cell membranes of epithelial, endothelial, smooth muscle, glial and neuronal
      cells. Confirming efficiency of GWAS with DNA-pooling approach by detection of
      the known LOXL1 locus, our study data show evidence for association of CNTNAP2
      with PEX syndrome and PEXG in German patients.

PMID- 20808328
TI  - The transcobalamin (TCN2) 776C>G polymorphism affects homocysteine concentrations
      among subjects with low vitamin B(12) status.
AB  - BACKGROUND/OBJECTIVES: Methionine synthase catalyzes the conversion of 5
      methyltetrahydrofolate to tetrahydrofolate and homocysteine (Hcy) to methionine
      using vitamin B(12) as a cofactor. Transcobalamin is the main transporter of
      vitamin B(12) from blood into cells. This study was undertaken to assess the
      relationship between the transcobalamin P259R (TCN2 776C>G) polymorphism and both
      serum vitamin B(12) and total Hcy (tHcy) levels. SUBJECTS/METHODS: The population
      comprised 613 men from Northern Ireland, aged 30-49 years, for whom tHcy, serum
      vitamin B(12) and serum folate concentrations were available. TCN2 776C>G
      genotypes were determined using a TaqMan 5' nuclease Real-Time PCR assay.
      Standard statistical tests of association were applied to assess the
      relationships between the polymorphism and phenotypic variables. RESULTS: The
      TCN2 776CC homozygous genotype was associated with lower serum vitamin B(12)
      concentrations compared with the 776CG (P(unadjusted)=0.01; P(adjusted)=0.03) and
      776GG genotypes (P(unadjusted)=0.015; P(adjusted)=0.045). Among individuals with
      vitamin B(12) concentrations in the lower half of the distribution, tHcy
      concentrations were higher in TCN2 776GG homozygotes than in individuals with the
      other genotypes (P(unadjusted)=0.015; P(adjusted)=0.06). CONCLUSIONS: These data
      suggest that, relative to transcobalamin with arginine at position 259 (776G),
      transcobalamin with proline at this position (776C) is either more efficient at
      vitamin B(12) transport from blood to tissues or has higher affinity for vitamin
      B(12). Furthermore, vitamin B(12) status influences the relationship between TCN2
      776C>G genotype and tHcy concentrations. Thus, the TCN2 776C>G polymorphism may
      contribute to the risk of pathologies associated with a low B(12), and high tHcy
      phenotype.

PMID- 20808329
TI  - Diet and weight gain characteristics of pregnant women with gestational diabetes.
AB  - BACKGROUND/OBJECTIVES: To determine if women with gestational diabetes (GD)
      modify their diet and nutrient intake in late pregnancy and gain more weight
      during pregnancy compared with women without GD. SUBJECTS/METHODS: Food and
      nutrient intake of 3613 pregnant women was studied using food frequency
      questionnaires from the Type I Diabetes Prediction and Prevention Nutrition
      Study. RESULTS: D was reported in 4.8% of the participating women (n=174). Women
      with GD gained less weight during pregnancy than those unaffected by GD (mean 9.4
      vs 12.6 kg, P<0.001). Women with GD consumed more milk products (84 vs 76 g/MJ,
      P=0.002), cereal products (21 vs 18 g/MJ, P<0.001), vegetables (32 vs 22 g/MJ,
      P<0.001) and meat (16 vs 14 g/MJ, P<0.001) than unaffected women. The intake of
      protein (18 vs 16 percent of total daily energy intake, P<0.001) and dietary
      fibre (3.1 vs 2.4 g/MJ, P<0.001) was higher, whereas the intake of sugars (13.3
      vs 15.0 g/MJ, P<0.001) and saturated fatty acids (3.49 vs 3.98 g/MJ, P<0.001) was
      lower among women with GD. The nutrient density of the diet was higher in women
      with GD with higher intakes of vitamins A and D, folate and iron. CONCLUSIONS:
      The late pregnancy diet of women with GD differed considerably from that of
      unaffected women. Women with GD had a higher body weight at the beginning of the
      pregnancy, but they gained less weight during pregnancy. These findings indicate
      that abnormal glucose tolerance during pregnancy encourages women to modify their
      dietary habits towards healthier food choices.

PMID- 20808330
TI  - Neighbourhood-socioeconomic variation in women's diet: the role of nutrition
      environments.
AB  - BACKGROUND/OBJECTIVES: Living in socioeconomically disadvantaged neighbourhoods
      is associated with increased risk of a poor diet; however, the mechanisms
      underlying associations are not well understood. This study investigated whether
      selected healthy and unhealthy dietary behaviours are patterned by neighbourhood
      socioeconomic disadvantage, and if so, whether features of the neighbourhood
      nutrition environment explain these associations. SUBJECTS/METHODS: A survey was
      completed by 1399 women from 45 neighbourhoods of varying levels of socioeconomic
      disadvantage in Melbourne, Australia. Survey data on fruit, vegetable and fast
      food consumption were linked with data on food store locations (supermarket,
      greengrocer and fast-food store density and proximity) and within-store factors
      (in-store data on price and availability for supermarkets and greengrocers)
      obtained through objective audits. Multilevel regression analyses were used to
      examine associations of neighbourhood disadvantage with fruit, vegetable and fast
      food consumption, and to test whether nutrition environment factors mediated
      these associations. RESULTS: After controlling for individual-level demographic
      and socioeconomic factors, neighbourhood disadvantage was associated with less
      vegetable consumption and more fast-food consumption, but not with fruit
      consumption. Some nutrition environmental factors were associated with both
      neighbourhood disadvantage and with diet. Nutrition environmental features did
      not mediate neighbourhood-disadvantage variations in vegetable or fast-food
      consumption. CONCLUSIONS: Although we found poorer diets among women living in
      disadvantaged neighbourhoods in Melbourne, the differences were not attributable
      to less supportive nutrition environments in these neighbourhoods.

PMID- 20808331
TI  - Effects of a sphingolipid-enriched dairy formulation on postprandial lipid
      concentrations.
AB  - BACKGROUND: The digestion of sphingolipids (SL) is slow and is catalyzed by
      mucosal enzymes. Dietary SL was shown to inhibit cholesterol absorption and to
      lower plasma cholesterol, triglycerides (TG) and hepatic fat accumulation in
      animal models. AIM: A dairy formulation based on fractionation of buttermilk,
      which is enriched in milk polar lipids of which SL account for a large part is
      now available. In this study, we examined whether this formulation, when ingested
      with a standard breakfast, exerted a different influence on postprandial lipids
      than an equivalent control formulation lacking the polar milk lipids. METHODS: A
      total of 18 healthy male volunteers aged 22-65 years ingested a high-fat (40 g)
      standard breakfast together with a milk-like formulation containing 975 mg of
      milk SL (A) or the control formulation (B). Postprandial levels of TG, total, low
      density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol,
      apolipoprotein AI (ApoAI), ApoB, glucose and insulin were measured 1 to 7 h after
      the meal. RESULTS: No difference was seen between experimental and control groups
      in postprandial levels of TG, insulin, ApoA1 or ApoB. After 1 hour there was a
      trend of lower cholesterol concentrations in large TG-rich lipoproteins after
      formulation A. CONCLUSION: The SL-rich buttermilk drink may affect cholesterol
      concentrations in TG-rich lipoproteins, but has no effect on postprandial TG
      after a breakfast with butter fat as the major lipid.

PMID- 20808332
TI  - Development of a lifestyle-diet quality index for primary schoolchildren and its
      relation to insulin resistance: the Healthy Lifestyle-Diet Index.
AB  - OBJECTIVE: The aim of this work was to develop an index that evaluates the degree
      of adherence to existing dietary and lifestyle guidelines for primary school-aged
      children (Healthy Lifestyle-Diet Index (HLD-Index)) and examine its relationship
      with selected nutrient intake and insulin resistance (IR). METHODS: Ten
      components were used to develop the HLD-Index. Scores from 0 to 4 were assigned
      to all components. The HLD-Index total score ranged between 0 and 40. A sample of
      729 schoolchildren from Greece aged 10-12 years (The Healthy Growth Study) was
      used to evaluate the validation of the proposed index. RESULTS: The overall
      mean+/-standard deviation of the HLD-Index score was 20+/-4.4. Higher HLD-Index
      scores were associated with lower proportion of children having intakes lower
      than Estimated Average Requirements by Institute of Medicine. On the basis of the
      cutoff point of 3.16 for homeostasis model assessment of IR, 20.9% of
      participants were found to be insulin resistant. After adjusting for potential
      confounders, logistic regression showed that a 1 unit increase in the score is
      associated with almost 8% lower odds for being insulin resistant. The cutoff
      point analysis revealed that score equal to or lower than 21 best discriminates
      children with IR from those without IR. On the basis of this cutoff point, the
      sensitivity of the HLD-Index was 70% and the corresponding specificity was 47%.
      CONCLUSIONS: The proposed HLD-Index could be used by public health policy makers
      and other health-care professionals to identify subgroups in the population with
      poor diet-lifestyle habits who are at increased probability for IR.

PMID- 20808333
TI  - The effects of phytosterols present in natural food matrices on cholesterol
      metabolism and LDL-cholesterol: a controlled feeding trial.
AB  - BACKGROUND/OBJECTIVES: Extrinsic phytosterols supplemented to the diet reduce
      intestinal cholesterol absorption and plasma low-density lipoprotein (LDL)
      cholesterol. However, little is known about their effects on cholesterol
      metabolism when given in native, unpurified form and in amounts achievable in the
      diet. The objective of this investigation was to test the hypothesis that
      intrinsic phytosterols present in unmodified foods alter whole-body cholesterol
      metabolism. SUBJECTS/METHODS: In all, 20 out of 24 subjects completed a
      randomized, crossover feeding trial wherein all meals were provided by a
      metabolic kitchen. Each subject consumed two diets for 4 weeks each. The diets
      differed in phytosterol content (phytosterol-poor diet, 126 mg phytosterols/2000
      kcal; phytosterol-abundant diet, 449 mg phytosterols/2000 kcal), but were
      otherwise matched for nutrient content. Cholesterol absorption and excretion were
      determined by gas chromatography/mass spectrometry after oral administration of
      stable isotopic tracers. RESULTS: The phytosterol-abundant diet resulted in lower
      cholesterol absorption (54.2+/-2.2% (95% confidence interval 50.5%, 57.9%) vs
      73.2+/-1.3% (69.5%, 76.9%), P<0.0001) and 79% higher fecal cholesterol excretion
      (1322+/-112 (1083.2, 1483.3) vs 739+/-97 mg/day (530.1, 930.2), P<0.0001)
      relative to the phytosterol-poor diet. Plasma lathosterol/cholesterol ratio rose
      by 82% (from 0.71+/-0.11 (0.41, 0.96) to 1.29+/-0.14 MUg/mg (0.98, 1.53),
      P<0.0001). LDL-cholesterol was similar between diets. CONCLUSIONS: Intrinsic
      phytosterols at levels present in a healthy diet are biologically active and have
      large effects on whole-body cholesterol metabolism not reflected in circulating
      LDL. More work is needed to assess the effects of phytosterol-mediated fecal
      cholesterol excretion on coronary heart disease risk in humans.

PMID- 20808334
TI  - Should waist circumference be used to identify metabolic disorders than BMI in
      South Korea?
AB  - Although indicators of central obesity have been suggested as a better
      alternative to body mass index (BMI), yet mixed results exist. This study
      examined whether waist circumference (WC) was better in identifying metabolic
      disorders than BMI at two time points. This study used nationally representative
      1998 and 2005 Korea National Health and Nutrition Examination Survey data sets.
      Odds ratios from logistic regressions and area under the curves (AUC) were
      calculated. BMI and WC showed similar level of odds ratios (1.1-1.6) to diabetes,
      hypertension, dyslipidemia and having two or three metabolic syndrome criteria.
      The AUC comparison, however, indicated that, in only women, WC was a better
      discriminator for diabetes, hypertension and having two or three metabolic
      syndrome criteria. No meaningful differences were found between 1998 and 2005.
      Prospective studies to weigh practical and clinical relevance are needed to
      assert the use of WC over BMI in clinical and public health settings.

PMID- 20808335
TI  - Comparison of two methods for identifying dietary patterns associated with
      obesity in preschool children: the GENESIS study.
AB  - BACKGROUND/OBJECTIVES: The aim of this work was to identify dietary patterns
      based on reduced rank regression (RRR) and principal component analysis (PCA) and
      to evaluate the association of these patterns with the prevalence of childhood
      obesity. SUBJECTS/METHODS: A sample of 2317 toddlers and preschoolers from Greece
      (Growth, Exercise and Nutrition Epidemiological Study In preSchoolers) was used.
      In total, 12 food groups were used as predictors of RRR and PCA. Nutrients such
      as total fat, simple carbohydrate and fiber intake were used as response
      variables to apply RRR. RESULTS: One factor/pattern was retained from RRR and PCA
      in order to ensure the comparability of the methods. The pattern derived from PCA
      was mainly characterized by consumption of fruits, vegetables, legumes, fish and
      seafood, grains and oils. This pattern explained 12.5% of the total variation in
      food groups. On the other hand, the pattern extracted from RRR was mainly
      characterized by reduced consumption of fruits, vegetables and legumes, and by
      increased consumption of sweets and red meat. The pattern derived from RRR
      explained 8.2% of the total variation in food groups. Simple and multiple
      logistic regression revealed that the pattern extracted from RRR is significantly
      associated with the prevalence of childhood obesity (OR=1.11, 95% CI: 1.00-1.28
      for each unit increase of dietary pattern) as opposed to the pattern derived from
      PCA. CONCLUSIONS: The preferable technique to derive dietary patterns related to
      childhood obesity seems to be RRR compared with PCA.

PMID- 20808336
TI  - Penetration of nutrition information on food labels across the EU-27 plus Turkey.
AB  - OBJECTIVES: The European Union (EU)-funded project Food Labelling to Advance
      Better Education for Life (FLABEL) aims to understand how nutrition information
      on food labels affects consumers' dietary choices and shopping behaviour. The
      first phase of this study consisted of assessing the penetration of nutrition
      labelling and related information on various food products in all 27 EU Member
      States and Turkey. METHODS: In each country, food products were audited in three
      different types of retailers to cover as many different products as possible
      within five food and beverage categories: sweet biscuits, breakfast cereals, pre
      packed chilled ready meals, carbonated soft drinks and yoghurts. RESULTS: More
      than 37 000 products were audited in a total of 84 retail stores. On average, 85%
      of the products contained back-of-pack (BOP) nutrition labelling or related
      information (from 70% in Slovenia to 97% in Ireland), versus 48% for front-of
      pack (FOP) information (from 24% in Turkey to 82% in the UK). The most widespread
      format was the BOP tabular or linear listing of nutrition content. Guideline
      daily amounts labelling was the most prevalent form of FOP information, showing
      an average penetration of 25% across all products audited. Among categories,
      breakfast cereals showed the highest penetration of nutrition-related
      information, with 94% BOP penetration and 70% FOP penetration. CONCLUSIONS:
      Nutrition labelling and related information was found on a large majority of
      products audited. These findings provide the basis for subsequent phases of
      FLABEL involving attention, reading, liking, understanding and use by consumers
      of different nutrition labelling formats.

PMID- 20808337
TI  - School lunch and learning behaviour in primary schools: an intervention study.
AB  - BACKGROUND/OBJECTIVES: In addition to the nutritional benefits of healthier
      school food, anecdotes describe improvements in children's behaviour and
      educational outcomes when school food or the school dining room environment is
      improved. This study hypothesized that a school food and dining room intervention
      would improve pupils' learning-related classroom behaviour. SUBJECTS/METHODS: A
      controlled intervention trial involving six primary schools matched in triplets
      and randomly assigned to a 12-week intervention (promotion of healthier school
      food at lunchtime and changes in the school dining environment) or 12-week wait
      listed control group. Study outcome was learning-related behaviours measured in a
      random sample of 146 pupils in years 3-5. RESULTS: On-task and off-task
      behaviours were observed and used as proxy measures for concentration and
      disengagement (disruption), respectively. Teacher-pupil on-task engagement was
      3.4 times more likely in the intervention schools compared with the control
      schools (adjusted model odds ratio (OR)=3.40 (95% confidence interval (CI)=1.56,
      7.36), P=0.009). However, on-task pupil-pupil behaviour was less likely in the
      intervention group (adjusted model OR=0.45 (95% CI=0.28, 0.70), P<0.001).
      Similarly, off-task pupil-pupil behaviour was more likely in the intervention
      group than in the control group in both the unadjusted model (OR=2.18 (95%
      CI=1.52, 3.13), P<0.001) and the adjusted model (OR=2.28 (95% CI=1.25, 4.17),
      P=0.007). CONCLUSIONS: This study offers some support for the hypothesis that a
      school food and dining room intervention can have a positive impact on pupils'
      alertness. However, if raised alertness is not channelled and supervised, it may
      result in increased off-task behaviour when pupils are working together.

PMID- 20808339
TI  - Statistical fluctuations of coherent and incoherent intensity in random lasers
      with nonresonant feedback.
AB  - We report on intensity fluctuations of a coherent random laser based on
      incoherent feedback via nonresonant multiple scattering. We quantify the spectral
      line shape fluctuations in terms of correlations of an individual spectrum with
      the ensemble-averaged spectrum, which infers the signature of the gain profile of
      the medium. These correlations are studied in relation to the intensity of the
      highest coherent modes. We evaluate the distribution of the ratio of the coherent
      and incoherent fractions in the emission, after independently assessing their
      statistics. Finally, these intensity fluctuations are graphically represented in
      a single scatter plot, the centroid of which can be used as a characterization
      parameter for the laser.

PMID- 20808338
TI  - Environmental contaminants as biomarkers of fish intake: a case for hair mercury
      concentrations.

PMID- 20808340
TI  - On the use of slow light for enhancing waveguide properties.
AB  - On the basis of a general analysis of waveguides containing a dispersive
      material, we identify conditions under which slow-light propagation may enhance
      the gain, absorption, or phase change. The enhancement is shown to depend on the
      slow-light mechanism and the translational symmetry of the waveguide. A
      combination of material and waveguide dispersion may strongly enhance the control
      of light speed, e.g., using electromagnetically induced transparency in quantum
      dots embedded in a photonic crystal waveguide.

PMID- 20808341
TI  - Hollow core fiber with an octave spanning bandgap.
AB  - We thoroughly compare the out-of-plane bandgaps generated by three realistic two
      dimensional lattices: a triangular and a square arrangement of holes and a
      triangular arrangement of rods. We demonstrate that, for any given hole-diameter
      to-pitch ratio d/Lambda, the triangular arrangement of interconnected resonators
      generates the widest possible bandgap along the air line, and we propose a
      physical interpretation explaining these results. The design of a hollow core
      photonic bandgap fiber based on such a lattice and able to transmit light with
      sub-decibel-per-meter losses over an octave of frequencies is presented for the
      first time, to the best of our knowledge.

PMID- 20808343
TI  - Separating the scattering and absorption coefficients using the real and
      imaginary parts of the refractive index with low-coherence interferometry.
AB  - We present an analytical method that yields the real and imaginary parts of the
      refractive index (RI) from low-coherence interferometry measurements, leading to
      the separation of the scattering and absorption coefficients of turbid samples.
      The imaginary RI is measured using time-frequency analysis, with the real part
      obtained by analyzing the nonlinear phase induced by a sample. A derivation
      relating the real part of the RI to the nonlinear phase term of the signal is
      presented, along with measurements from scattering and nonscattering samples that
      exhibit absorption due to hemoglobin.

PMID- 20808344
TI  - Blazing evanescent grating orders: a spectral approach to beating the Rayleigh
      limit.
AB  - We develop a way to enhance the amplitudes of the nonpropagating evanescent
      orders of resonant dielectric gratings. We use this blazing to design gratings
      with spectra tailored to generate steerable sub-Rayleigh field concentrations on
      a surface. We investigate the enhancement and customization of evanescent fields
      necessary to create a virtual and passive scanning probe with no moving parts.
      Spot size can be decreased 1 order of magnitude below the free-space Rayleigh
      limit.

PMID- 20808342
TI  - Spatial-domain low-coherence quantitative phase microscopy for cancer diagnosis.
AB  - A microscopy technique, spatial-domain low-coherence quantitative phase
      microscopy (SL-QPM) is proposed for speckle-free, quantitative phase imaging of
      subcellular structures with subnanometer sensitivity. We quantified, for the
      first time to our knowledge, the refractive index of the cell nuclei on original
      unmodified histology specimens. We demonstrate that the refractive index of cell
      nucleus is highly sensitive in detecting cancer, especially in histologically
      normal-appearing cells from cancer patients. Because this technique is sensitive
      and does not require special sample processing, it can be disseminated to all
      clinical settings.

PMID- 20808345
TI  - In situ loss measurement of direct UV-written waveguides using integrated Bragg
      gratings.
AB  - The propagation loss of a direct UV-written silica-on-silicon waveguide is
      measured using an elegant nondestructive method. The technique uses integrated
      Bragg grating structures, which are observed from opposing launch directions to
      obtain information about the optical power at different positions along the
      length of the waveguide. Critically, the technique is ratiometric and independent
      of coupling loss and grating variability. This high-precision measurement is
      suitable for low-loss planar waveguides. From this data, the propagation loss of
      the UV-written waveguides was observed to be 0.235+/-0.006 dB/cm.

PMID- 20808346
TI  - Speckle reduction using a motionless diffractive optical element.
AB  - Speckle reduction by moving diffuser has been previously studied in display
      systems with coherent light sources, such as lasers. In this Letter, we propose a
      motionless diffractive optical element (DOE) for speckle reduction. The DOE was
      designed based on finite-element method simulations, fabricated using
      micromachining technology, and characterized for despeckle efficiency.
      Experiments using a DOE with two gratings have indicated that the speckle was
      suppressed to 50%, which shows fair agreement with theoretical analysis. With
      some modification of this DOE, the speckle noise can be reduced to 10% according
      to the theory.

PMID- 20808347
TI  - Optical manipulation and transport of microparticles on silicon nitride microring
      resonator-based add-drop devices.
AB  - We demonstrate optical manipulation and transport of 1 microm sized polystyrene
      particles on silicon nitride microring-resonator-based add-drop devices in an
      integrated optofluidic chip. By tuning the input laser wavelength and upon
      certain resonance quality factors, we observe microparticles (i) transported to
      the throughput port, (ii) routed to the microring and trapped in round trips, and
      (iii) transported to the drop port. We investigate the microparticle velocity at
      various laser wavelengths and in various spatial regions of the devices with
      different resonance quality factors. Such a device can act as a particle add-drop
      filter for "particle circuits" in lab-on-a-chip applications.

PMID- 20808348
TI  - 37.4 fs pulse generation in an Er:fiber laser at a 225 MHz repetition rate.
AB  - We report 37.4 fs pulse generation from a ring-cavity Er:fiber laser at a
      repetition rate of 225 MHz. The spectral bandwidth of the pulse is 135 nm. The
      single-pulse energy is 0.31 nJ.

PMID- 20808349
TI  - Time evolution of the Lamb shift.
AB  - The time evolution of the Lamb shift that accompanies the real photon emission is
      studied for the first time (to our knowledge). The investigation of the explicit
      time dependence of the Lamb shift becomes possible because the self-energy of the
      free electron, which is divergent, is subtracted from the Hamiltonian after a
      unitary transformation. The Lamb shift can then be separated into two parts: one
      is the time-independent shift due to the virtual photon exchange, and the other
      is the time-dependent shift due to the real photon emission. The time evolution
      depends on the nature of the coupling spectrum of the reservoir.

PMID- 20808350
TI  - Optimum access waveguide width for 1 x N multimode interference couplers on
      silicon nanomembrane.
AB  - We derived an analytical formula for the optimum width of the access waveguides
      of 1 x N multimode interference (MMI) couplers. Eigenmode-decomposition-based
      simulations show that the optimum width relation corresponds to the points of
      diminishing returns in both insertion loss and output uniformity versus access
      waveguide width. We fabricate and characterize 1 x 12 MMI couplers on a
      nanomembrane of silicon-on-insulator substrate. The experimental investigations
      demonstrate that the analytical results can be reliably used as a design rule for
      MMI couplers with large number of outputs.

PMID- 20808351
TI  - 110 km transmission of 160 Gbit/s RZ-DQPSK signals by midspan polarization
      insensitive optical phase conjugation in a Ti:PPLN waveguide.
AB  - We demonstrate 160 Gbit/s return-to-zero (RZ) differential quarternary phase
      shift keying (DQPSK) signal transmission over a 110 km single-mode fiber by
      taking advantage of mid-span optical phase conjugation (OPC). The technique is
      based on nonlinear wavelength conversion by cascaded second harmonic and
      difference frequency generation in a Ti:PPLN waveguide. Error-free operation with
      a negligible optical signal-to-noise ratio penalty for the signal after the OPC
      transmission without and with polarization scrambling was achieved. The results
      also show the polarization insensitivity of the OPC system using a polarization
      diversity scheme.

PMID- 20808352
TI  - CaF2 whispering-gallery-mode-resonator stabilized-narrow-linewidth laser.
AB  - A fiber laser is stabilized by introducing a calcium fluoride (CaF(2)) whispering
      gallery-mode resonator as a filtering element in a ring cavity. It is set up
      using a semiconductor optical amplifier as a gain medium. The resonator is
      critically coupled through prisms, and used as a filtering element to suppress
      the laser linewidth. A three-cornered-hat method is used and shows a stability of
      10(-11) after 10 micros. Using the self-heterodyne beat technique, the linewidth
      is determined to be 13 kHz. This implies an enhancement factor of 10(3) with
      respect to the passive cavity linewidth.

PMID- 20808353
TI  - Enhanced detection of fluorescent nanospheres using two-channel radially
      polarized surface plasmon microscopy.
AB  - We detected single dye-stained latex nanospheres as small as 20 nm using a two
      detection channel modified surface plasmon microscope. We found that a radially
      polarized incident beam leading to excitation of well-focused surface plasmons
      induces both fluorescence and elastic linear scattering from the spheres. The two
      complementary emitted signals were detected in parallel by the two separated
      channels, leading to well-colocalized images. We obtained high spatial
      resolutions for both channels down to 250 nm in the lateral direction and 300 nm
      along the longitudinal axis. We believe this multimodal microscope can be useful
      to track nano objects and to compensate for intermittent fluorescence, thanks to
      a permanently activated parallel scattering detection channel.

PMID- 20808354
TI  - Symmetry in the elementary scattering of surface plasmon polaritons and a
      generalized symmetry principle.
AB  - In the elementary scattering of surface plasmon polaritons (SPPs) at individual
      subwavelength (sub-lambda) objects on metallic surfaces, the in-plane
      transmission and reflection of SPPs are shown to be two related scattering
      processes and to satisfy some novel symmetry relations, provided that the objects
      are mirror symmetric and are narrow enough (<0.1lambda approximately). To
      interpret these symmetry relations, a new generalized symmetry principle for the
      scattered field is put forward, which is much less limited than the classical one
      and is shown to have wide applications for other sub-lambda scattering problems.

PMID- 20808355
TI  - Broadband terahertz fiber directional coupler.
AB  - We present the design of a short broadband fiber directional coupler for
      terahertz (THz) radiation and demonstrate a 3 dB coupler with a bandwidth of 0.6
      THz centered at 1.4 THz. The broadband coupling is achieved by mechanically
      downdoping the cores of a dual-core photonic crystal fiber by microstructuring
      the cores. This is equivalent to chemical downdoping but is easier to realize
      experimentally.

PMID- 20808357
TI  - Reduction of timing jitter in passively Q-switched microchip lasers using self
      injection seeding.
AB  - We present an efficient, simple, and passive technique for the reduction of
      timing jitter in passively Q-switched microchip lasers via self-injection seeding
      using a fiber delay line. The presented approach mitigates one inherent issue of
      passively Q-switched lasers without the need for active stabilization. At a
      repetition rate of a few hundred kilohertz and pulse duration of approximately
      200 ps delivered by a microchip laser, the rms jitter is reduced from several
      nanoseconds down to 20 ps, hence, significantly below the pulse duration of the
      laser source.

PMID- 20808356
TI  - Performance comparison of Zr-based and Bi-based erbium-doped fiber amplifiers.
AB  - In this Letter, we present a comprehensive comparison of the performance of a
      zirconia-based erbium-doped fiber amplifier (Zr-EDFA) and a bismuth-based erbium
      doped fiber amplifier (Bi-EDFA). The experimental results reveal that a Zr-EDFA
      can achieve comparable performance to the conventional Bi-EDFA for C-band and L
      band operations. With a combination of both Zr and Al, we could achieve a high
      erbium-doping concentration of about 2800 ppm (parts per million) in the glass
      host without any phase separations of rare earths. The Zr-based erbium-doped
      fiber (Zr-EDF) was fabricated using in a ternary glass host, zirconia-yttria
      aluminum codoped silica fiber through a solution-doping technique along with
      modified chemical vapor deposition. At a high input signal of 0 dBm, a flat gain
      at average value of 13 dB is obtained with a gain variation of less than 2 dB
      within the wavelength region of 1530-1575 nm and using 2 m of Zr-EDF and 120 mW
      pump power. The noise figures are less than 9.2 at this wavelength region. It was
      found that a Zr-EDFA can achieve even better flat-gain value and bandwidth as
      well as lower noise figure than the conventional Bi-EDFA.

PMID- 20808358
TI  - Differential amplitude scanning for retinal imaging: a theoretical study.
AB  - A differential amplitude scanning system for ophthalmoscopy is described
      theoretically. The differential scanning ophthalmoscope (DSO) samples the retina
      with two laterally displaced spots. The signal measured is the difference between
      the irradiance from these two locations. The theoretical analysis of the DSO
      shows it offers increased contrast at high spatial frequencies and only weak
      contributions from the low frequencies. This enables high-gain, low-noise
      detection that maximizes contrast.

PMID- 20808359
TI  - High-speed digital-image correlation method: comment.
AB  - We comment on the recent letter by Wang et al. [Opt. Lett. 34, 1955 (2009)], in
      which the authors presented a high-speed digital image correlation (DIC) method.
      We consider that the so-called high-speed DIC method has considerable
      deficiencies and that the Letter is misleading in terms of applicability and
      measurement accuracy as well as processing speed.

PMID- 20808360
TI  - Integrated intravascular ultrasound and photoacoustic imaging scan head.
AB  - The combination of intravascular ultrasound and intravascular photoacoustic
      imaging has been proposed for improving the diagnosis of arterial diseases. We
      describe a novel scan-head design for implementing such multimodality imaging.
      The proposed device has the potential to achieve a sufficiently small size for
      clinical intravascular applications. The design aims for efficient image data
      acquisition for facilitating real-time three-dimensional imaging and reducing the
      required laser pulse repetition frequency. The integrated scan head consists of a
      single-element, ring-shaped transducer for sideward ultrasound transmission, a
      multimode fiber with a cone-shaped mirror for optical illumination, and a single
      polymer microring with mechanical scanning. The phantom imaging and some
      experimental results are presented. A microring array can be realized in the
      future to achieve high-frame-rate intravascular multimodality imaging.

PMID- 20808361
TI  - Discrete and surface solitons in photonic graphene nanoribbons.
AB  - We analyze localization of light in honeycomb photonic lattices restricted in one
      dimension, which can be regarded as an optical analog of graphene nanoribbons. We
      discuss the effect of lattice topology on the properties of discrete solitons
      excited inside the lattice and at its edges. We discuss a type of soliton
      bistability, geometry-induced bistability, in the lattices of a finite extent.

PMID- 20808362
TI  - Observation of Lamb shift and modified spontaneous emission dynamics in the
      YBO3:Eu3+ inverse opal.
AB  - The study of Lamb shift plays a unique role in quantum electrodynamics because it
      provides an excellent test of the theory on photonic crystals (PCs). In this
      Letter, we present the first observation of large Lamb shift in the YBO(3):Eu(3+)
      inverse opals fabricated by the polystyrene templating method. In addition, it is
      very interesting to observe that the luminescent dynamics of Eu(3+) decayed with
      a faster power law (t(-3)), followed by a slower exponential process due to the
      coexistence of the diffusion field and the propagating field in the PCs.

PMID- 20808363
TI  - Design and characterization of microring reflectors with a waveguide crossing.
AB  - We present a novel design of a wavelength-selective reflector using a microring
      resonator integrated with a low-loss, low-crosstalk waveguide crossing.
      Functioning as a reflective notch filter, it can be used for optical
      communications and for sensor applications. The device is simulated using the
      transfer-matrix method combined with a two-dimensional finite-difference mode
      solver and is fabricated by a CMOS-compatible silicon-on-insulator technology.
      The measurement shows an extinction ratio greater than 25 dB and a resonance
      wavelength temperature dependence of 0.09 nm/K.

PMID- 20808364
TI  - Polarization rotation due to femtosecond filamentation in an atomic gas.
AB  - The linear-to-elliptical transformation of a 400 nm femtosecond-probe pulse in
      the birefringent filament in argon of an 800 nm linearly polarized femtosecond
      pump pulse is studied numerically and experimentally. The rotation of the probe
      elliptical polarization is the largest in the high-intensity filament core. With
      propagation, the rotated radiation diffracts outward by the pump-produced plasma.
      The transmission of the analyzer crossing the probe's polarization is maximum at
      the pump-probe angle of 45 degrees and gives equal values for each pair of angles
      symmetrically situated at both sides of the maximum.

PMID- 20808365
TI  - Computational study of 3-5 microm source created by using supercontinuum
      generation in As2S3 chalcogenide fibers with a pump at 2 microm.
AB  - We present simulation results for supercontinuum generation using As(2)S(3)
      chalcogenide photonic crystal fibers. We found that more than 25% of input power
      can be shifted into the region between 3 microm and 5 microm using a pump
      wavelength of 2 microm with a peak power of 1 kW and an FWHM of 500 fs. The broad
      dispersion profile and high nonlinearity in As(2)S(3) chalcogenide glass are
      essential for this application.

PMID- 20808366
TI  - Multiplexed fluorescence lifetime measurements by frequency-sweeping Fourier
      spectroscopy.
AB  - We report simultaneous measurements of fluorescence lifetimes at multiple
      excitation wavelengths with a Fourier transform frequency domain fluorescence
      lifetime spectrometer. The spectrometer uses a Michelson interferometer with its
      differential optical path length scanning at a 22,000 Hz scan rate. The scan
      speed of the optical delay varies linearly during each scan and creates
      interference modulations that sweep from -150 to 150 MHz in 45.5 micros. The
      frequency-sweeping modulation allows nanosecond fluorescence lifetime
      measurements within 45.5 micros. Because the interference modulation frequency is
      wavelength dependent, under the Fourier multiplexing principle, the spectrometer
      can perform lifetime measurements on multiple excitation wavelengths
      simultaneously.

PMID- 20808367
TI  - Quantum-confined Stark effect measurements in Ge/SiGe quantum-well structures.
AB  - We investigate the room-temperature quantum-confined Stark effect in Ge/SiGe
      multiple quantum wells (MQWs) grown by low-energy plasma-enhanced chemical vapor
      deposition. The active region is embedded in a p-i-n diode, and absorption
      spectra at different reverse bias voltages are obtained from optical
      transmission, photocurrent, and differential transmission measurements. The
      measurements provide accurate values of the fraction of light absorbed per well
      of the Ge/SiGe MQWs. Both Stark shift and reduction of exciton absorption peak
      are observed. Differential transmission indicates that there is no thermal
      contribution to these effects.

PMID- 20808368
TI  - Kerr-lens mode locking with minimum nonlinearity using gain-matched output
      couplers.
AB  - Broadband Kerr-lens mode locking is demonstrated at greatly reduced mode-locking
      strength with a gain-matched output coupler that compensates for gain filtering.
      Already at very low pump powers, slightly above the cw lasing threshold, we are
      able to initiate robust mode locking and generate <8 fs output pulses from a
      Ti:sapphire laser with good beam quality. Because dielectric coatings offer
      flexible design capabilities, this approach is applicable to various lasers with
      different gain media to extract pulses covering the full gain spectrum with
      minimum saturable absorber action.

PMID- 20808370
TI  - Pressure-controlled phase matching to third harmonic in Ar-filled hollow-core
      photonic crystal fiber.
AB  - We report tunable third-harmonic generation (THG) in an Ar-filled hollow-core
      photonic crystal fiber, pumped by broadband <2 microJ, 30 fs pulses from an
      amplified Ti:sapphire laser system. The overall dispersion is precisely
      controlled by balancing the negative dielectric susceptibility of the waveguide
      against the positive susceptibility of the gas. We demonstrate THG to a higher
      order guided mode and show that the phase-matched UV wavelength is tunable by
      adjusting the gas pressure.

PMID- 20808369
TI  - >400 kHz repetition rate wavelength-swept laser and application to high-speed
      optical frequency domain imaging.
AB  - We demonstrate a high-speed wavelength-swept laser with a tuning range of 104 nm
      (1228-1332 nm) and a repetition rate of 403 kHz. The design of the laser utilizes
      a high-finesse polygon-based wavelength-scanning filter and a short-length
      unidirectional ring resonator. Optical frequency domain imaging of the human skin
      in vivo is presented using this laser, and the system shows sensitivity of higher
      than 98 dB with single-side ranging depth of 1.7 mm over 4 dB sensitivity roll
      off.

PMID- 20808371
TI  - Flat-plateau supercontinuum generation in liquid absorptive medium by femtosecond
      filamentation.
AB  - We have studied filamentation and supercontinuum generation by focusing the
      intense femtosecond laser pulses into an absorptive medium (CuSO(4) aqueous
      solution). A broad spectrum from 350 to 950 nm with a flat plateau spanning
      approximately from 450 to 700 nm with a flatness of 9% is obtained without any
      additional filters. The results indicate that the absorptive medium not only
      suppresses the strong surplus femtosecond laser signal but also flattens the
      supercontinuum spectrum efficiently.

PMID- 20808372
TI  - Defect modes in defective parity-time symmetric periodic complex potentials.
AB  - Defect modes are studied in parity-time (PT) symmetric periodic complex
      potentials for both positive and negative defects. Such new kinds of linear
      localized modes may conserve their energy or endure gain or loss upon
      propagating. The existence domain of the conserved modes would be prolonged by
      positive defects or shortened by negative defects, and the dissipative modes
      would appear before the phase transition point of the PT symmetric potential at
      stronger negative defects.

PMID- 20808373
TI  - Demonstration of terahertz frequency-dependent field transformation in an
      irregular waveguide structure with direct measurement of the internal electric
      fields.
AB  - We demonstrate irregular scattering structure frequency-dependent field control
      at terahertz frequencies by means of a TM(10) to TM(30) mode converter designed
      for operation near 300 GHz and fabricated out of lithium niobate. Imaging of the
      electric fields in the sample, with a Fourier analysis of the time domain signal,
      yielded the performance as a function of frequency.

PMID- 20808374
TI  - Sectional image reconstruction in optical scanning holography using a random
      phase pupil.
AB  - A method is presented for the reconstruction of sectional images without the out
      of-focus haze from a hologram generated by optical scanning holography. A random
      phase pupil is adopted in the process of recovering individual sections from the
      hologram. The main idea of this approach is to recover a prescribed section while
      dispersing the energy from other sections into "specklelike patterns," which can
      be eliminated subsequently by averaging of multiple section images.

PMID- 20808375
TI  - Surface-enhanced Raman scattering microchip fabricated by femtosecond laser.
AB  - We report a surface-enhanced Raman scattering (SERS) microchip that is capable of
      measuring SERS signals of liquid samples with high sensitivity. The microdevice
      is an integration of a silicon-based SERS substrate, a multimode optical fiber
      (MMF), and a microchannel embedded in the photosensitive glass fabricated by the
      femtosecond laser followed by thermal treatment, wet etching, and annealing. The
      performance of the SERS microchip is evaluated by measuring rhodamine 6G using a
      632.8 nm He-Ne laser at 4.3 mW excitation power, which reveals that the detection
      limit is lower than 10(-10) M at a 1 s short accumulation time.

PMID- 20808376
TI  - Electro-optical tunable time delay and advance in silicon microring resonators.
AB  - We demonstrate electro-optical tunable time delay and advance in a silicon
      microring-resonator-based notch filter integrated with a lateral p-i-n diode. We
      tune the time delay and advance by controlling the coupling regimes from over- to
      under-coupling through carrier-injection-based free-carrier dispersion effect. We
      measure maximum time delay and advance of approximately -95 and approximately 96
      ps near critical coupling, with bandwidths of approximately 3.5 and approximately
      3 GHz, upon dc power consumption in the range of 1 mW. We model the transmission
      spectra and time delay/advance using the transfer-matrix method and analyze the
      time-intensity and time-bandwidth products, which show good agreement with our
      measurements.

PMID- 20808377
TI  - Fourth-order oriented partial-differential equations for noise removal of two
      photon fluorescence images.
AB  - We derive the fourth-order oriented partial-differential equations (PDEs) for
      noise removal of two-photon fluorescence images. We consider it from two aspects:
      one is based on a variational method; the other is based on controlling the
      diffusion direction. Our filtering model makes the diffusion along only the
      special orientation--decided via all the information in the established filtering
      window, so the edges are protected during filtering. Compared with related PDEs
      models, our model shows superior performance in terms of both objective criteria
      and subjective human vision via processing simulated and experimental noisy
      images.

PMID- 20808378
TI  - Effects of phosphor-based LEDs on vertical scanning interferometry.
AB  - High-power phosphor-based LEDs are replacing conventional white-light sources for
      vertical scanning interferometry, but the spectrum of the phosphor-based LED is
      different from that of the conventional light source. The phosphor-based LED has
      two peaks in its spectrum, while the conventional light source has only one peak
      in the Gaussian distribution. In this Letter, we investigate the effects of
      phosphor-based LEDs on vertical scanning interferometry. Our result shows that
      the use of a phosphor-based LED changes the fringe contrast function
      significantly, such that measurement repeatability decreases. We propose and
      demonstrate that a constraint on the input to the existing reconstruction
      algorithm improves the repeatability of the vertical scanning interferometer with
      a phosphor-based LED.

PMID- 20808379
TI  - Passive torque wrench and angular position detection using a single-beam optical
      trap.
AB  - The recent advent of angular optical trapping techniques has allowed for
      rotational control and direct torque measurement on biological substrates. Here
      we present a method that increases the versatility and flexibility of these
      techniques. We demonstrate that a single beam with a rapidly rotating linear
      polarization can be utilized to apply a constant controllable torque to a trapped
      particle without active feedback, while simultaneously measuring the particle
      angular position. In addition, this device can rapidly switch between a torque
      wrench and an angular trap. These features should make possible torsional
      measurements across a wide range of biological systems.

PMID- 20808380
TI  - In situ measurement and reconstruction in three dimensions of femtosecond
      inscription-induced complex permittivity modification in glass.
AB  - We demonstrate a new approach to in situ measurement of femtosecond-laser-pulse
      induced changes in glass, enabling the three-dimensional reconstruction of the
      induced complex permittivity modification. The technique can be used to provide
      single-shot and time-resolved quantitative measurements with a micrometer-scale
      spatial resolution.

PMID- 20808381
TI  - White-light LED clusters with high color rendering.
AB  - We established a model for spectra of LEDs at different drive currents. The
      simulation program of color rendering of white-light LED clusters has been
      developed, according to the principle of additive color mixture. The experimental
      results show that white/red LED clusters can realize color temperature untunable
      white light with a high color rendering index and high luminous efficacy and that
      neutral-white/red/blue LED clusters can realize color temperature tunable white
      light with a high color rendering index and high luminous efficacy.

PMID- 20808382
TI  - Observation of narrowband intrinsic spectra of Brillouin dynamic gratings.
AB  - We experimentally demonstrate that the reflection spectrum of a Brillouin dynamic
      grating in a polarization-maintaining fiber can be much narrower than the
      intrinsic linewidth of the stimulated Brillouin scattering, matching well with
      the theory of a fiber Bragg grating in terms of the linewidth and the
      reflectivity. A 3 dB bandwidth as narrow as 10.5 MHz is observed with the
      Brillouin dynamic grating generated in a 9 m uniform fiber.

PMID- 20808383
TI  - Transport of intensity phase imaging in a volume holographic microscope.
AB  - We demonstrate a method for single-shot quantitative phase imaging based on the
      transport of intensity equation (TIE) in a volume holographic microscope (VHM).
      The VHM system uses a multiplexed volume hologram to laterally separate images
      from different focal planes. This axial intensity information is then used to
      solve the TIE and recover object phase quantitatively. Further, we show improved
      phase recovery by using five multiplexed gratings in one hologram.

PMID- 20808384
TI  - All-solid-state cw sodium D2 resonance radiation based on intracavity frequency
      doubled self-Raman laser operation in double-end diffusion-bonded Nd3+:LuVO4
      crystal.
AB  - We report for the first time (to our knowledge) cw orange-yellow emission at 589
      nm from a compact double-end diffusion-bonded Nd(3+):LuVO(4) self-Raman laser
      with intracavity frequency doubling in LiB(3)O(5), pumped by an 880 nm diode
      laser. A 3.5 W cw orange-yellow emission with an overall diode-to-visible
      conversion efficiency of 13.3% is achieved through the use of an 18-mm-long
      double-ended diffusion-bonded Nd(3+):LuVO(4) crystal. The M(2) factors are 1.35
      and 1.74 in both the horizontal and vertical dimensions, respectively.

PMID- 20808385
TI  - Precise method for modifying birefringence of stress-induced high-birefringence
      fiber.
AB  - A precise method for modifying the birefringence of stress-induced high
      birefringence (Hi-Bi) fiber is demonstrated by side polishing a Panda-type fiber
      with a maximum polished length of at least 14 cm. The polishing depth is
      controlled with an accuracy of 0.1 microm by piezoelectric ceramic
      microdisplacement. The accuracy of the birefringence is of the order of 10(-6).
      This method allows high-quality Hi-Bi fiber segments to be conveniently
      implemented with low loss at any desired birefringence between 3.17 x 10(-4) and
      7.5 x 10(-5) in our experiment from one stress-induced Hi-Bi fiber and without
      changing the directions of the stress axes. The finite-element method is used to
      simulate the procedure, and the numerical results agree with the experiment.

PMID- 20808386
TI  - Q-switched resonantly diode-pumped Er3+:YAG laser with fiberlike geometry.
AB  - Crystalline fiberlike diode-pumped laser systems offer a convenient way to obtain
      compact, robust, and efficient operation whenever long active media are required.
      One of these cases is the diode-pumped Er(3+):YAG laser emitting at 1.6 microm,
      where long crystals are needed to avoid the upconversion processes. By resonantly
      pumping the (4)I(13/2) level around 1.53 microm, and by confining the pump
      radiation into the crystal by total internal reflection, a maximum output power
      of 14.5 W in cw mode is reached when pumped with approximately 40 W of absorbed
      power. In Q-switching mode, pulse energies of more than 8 mJ were obtained at a
      repetition rate of 90 Hz, limited by coating damage.

PMID- 20808387
TI  - Near-diffraction-limited flattop laser beam adaptively generated by stochastic
      parallel gradient descent algorithm.
AB  - We demonstrate the adaptive generation of a near-diffraction-limited flattop
      laser beam in the near field based on the stochastic parallel gradient descent
      algorithm and dual-phase-only liquid crystal spatial light modulators (LC-SLMs).
      One LC-SLM redistributes the intensity, and the other compensates the wavefront
      of the output beam. The experimental results show that approximately 69% of the
      power is enclosed in a region with less than 6% rms intensity variation. The 5mm
      diameter near-diffraction-limited output beam retains a flattop intensity
      distribution without significant diffraction peaks for a working distance of more
      than 30 cm.

PMID- 20808388
TI  - Binary parity-time-symmetric nonlinear lattices with balanced gain and loss.
AB  - We study nonlinear binary arrays composed of parity-time-symmetric optical
      waveguides with gain and loss. We demonstrate that such nonlinear binary lattices
      support stable discrete solitons, which can be adiabatically tuned and switched
      through nonlinear symmetry breaking by varying gain and loss parameters.

PMID- 20808389
TI  - Phase-transparent optical data exchange of 40 Gbit/s differential phase-shift
      keying signals.
AB  - We report the phase-transparent optical data exchange of differential phase-shift
      keying (DPSK) signals by exploiting the parametric depletion of nondegenerate
      four-wave mixing (FWM) in a highly nonlinear fiber. Theoretical analyses of
      nondegenerate FWM involving two signals and two pumps are presented. Analytical
      solutions are derived, indicating the exchange condition and the feasibility of
      phase-transparent data exchange. Optical data exchange between 10.7 Gbit/s non
      return-to-zero DPSK (NRZ-DPSK) and return-to-zero DPSK signals is implemented
      with a power penalty of approximately 1.5 dB at a bit-error rate (BER) of 10(-9).
      Moreover, we demonstrate phase-transparent optical data exchange between two 40
      Gbit/s NRZ-DPSK signals with a power penalty of approximately 4.5 dB at a BER of
      10(-9).

PMID- 20808390
TI  - Suppression of stimulated Raman scattering employing long period gratings in
      double-clad fiber amplifiers.
AB  - We report on the suppression of stimulated Raman scattering (SRS) in a double
      clad fiber amplifier using long-period gratings (LPGs). The LPGs, fabricated with
      a CO(2) laser, achieve SRS suppression by coupling the Stokes wavelength from the
      active core into the cladding. With only three LPGs inserted into a fiber pulse
      amplifier, the extractable Raman-free output power was nearly doubled. A
      numerical simulation of the setup shows good agreement with the experimental
      results.

PMID- 20808391
TI  - Higher-order dispersion compensation to enable a 3.6 micros wavelength
      maintaining delay of a 100 Gb/s DQPSK signal.
AB  - We demonstrate a method for dispersion slope compensation of a
      conversion/dispersion-based optical delay to enable 100 Gb/s operation based on a
      spatial light modulator and fiber Bragg gratings. A continuous delay of up to 3.6
      micros for 100, 80, and 20 Gb/s differential quadrature phase-shift-keyed (DQSPK)
      and 50, 40, and 10 Gb/s differential phase-shift-keyed (DPSK) waveforms is shown.
      A time-delay bit-rate product of approximately 360,000 for 100 Gb/s DQPSK with
      wavelength-maintaining operation is achieved.

PMID- 20808392
TI  - Use of tapered amplifier diode laser for biological-friendly high-resolution
      optical trapping.
AB  - A 1064 nm laser is commonly used for biological optical trapping. However, it has
      the problem of generating reactive oxygen species in the presence of a
      sensitizer, which leads to photo damage in biological samples. Here we
      constructed optical tweezers using a tapered amplifier diode laser that operates
      at 830 nm. Compared to a 1064 nm laser, this laser is friendly to live cells,
      eliminates photo damage associated with reactive oxygen species, and allows
      simultaneous two-photon fluorescence imaging of green fluorescent proteins in
      live mammalian cells. All these advantages could significantly benefit future
      application of this single molecule technique in biological studies.

PMID- 20808393
TI  - Pulse energy of 151 nJ from ultrafast thulium-doped chirped-pulse fiber
      amplifier.
AB  - We report on chirped-pulse amplification of an ultrafast thulium-doped fiber
      laser. Pulses with an energy of 3.3 nJ and a bandwidth-limited pulse duration of
      195 fs could be amplified to 151 nJ, which corresponds to an average power of 5.7
      W at 37.6 MHz pulse repetition rate. The maximum output power was limited by the
      available pump power. The pulses could be dechirped to a duration of 258 fs.

PMID- 20808394
TI  - Continuous-wave diamond Raman laser.
AB  - Continuous-wave operation of a diamond Raman laser is demonstrated. Low
      birefringence synthetic single-crystal diamond is used and is intracavity pumped
      by a Nd:YVO(4) laser. A cw output power of 200 mW is achieved at the Raman
      wavelength (1240 nm), and 1.6 W of on-time output power is obtained in quasi-cw
      mode. Losses in the diamond (approximately 1% per pass) and thermal effects in
      the Nd:YVO(4) limit the efficiency.

PMID- 20808395
TI  - Demonstration of the coupling of optofluidic ring resonator lasers with liquid
      waveguides.
AB  - Optofluidic lasers are of particular interest for lab-on-a-chip-type devices,
      with broad spectral tunability, convenient microfluidic integration, and a small
      footprint. Optofluidic ring resonator (OFRR) lasers are advantageous in terms of
      size but typically generate nondirectional emission that is of minimal practical
      use. We introduce two unique geometries for soft-lithography-based OFRR lasers-
      side-coupled rings and spiral rings--both of which can be produced in
      polydimethyl siloxane substrates with contact molding. These rings utilize
      evanescent and direct butt-coupling, respectively, to effectively couple the OFRR
      laser emission into microfluidic channels. A laser threshold of a few to tens of
      microJ/mm(2) is achieved.

PMID- 20808396
TI  - Fast and accurate algorithm for the computation of complex linear canonical
      transforms.
AB  - A fast and accurate algorithm is developed for the numerical computation of the
      family of complex linear canonical transforms (CLCTs), which represent the input
      output relationship of complex quadratic-phase systems. Allowing the linear
      canonical transform parameters to be complex numbers makes it possible to
      represent paraxial optical systems that involve complex parameters. These include
      lossy systems such as Gaussian apertures, Gaussian ducts, or complex graded-index
      media, as well as lossless thin lenses and sections of free space and any
      arbitrary combinations of them. Complex-ordered fractional Fourier transforms
      (CFRTs) are a special case of CLCTs, and therefore a fast and accurate algorithm
      to compute CFRTs is included as a special case of the presented algorithm. The
      algorithm is based on decomposition of an arbitrary CLCT matrix into real and
      complex chirp multiplications and Fourier transforms. The samples of the output
      are obtained from the samples of the input in approximately N log N time, where N
      is the number of input samples. A space-bandwidth product tracking formalism is
      developed to ensure that the number of samples is information-theoretically
      sufficient to reconstruct the continuous transform, but not unnecessarily
      redundant.

PMID- 20808397
TI  - Analysis of finite-sized guided-mode resonant gratings using the fast multipole
      boundary element method.
AB  - Guided-mode resonant grating filters are dispersive devices that utilize
      resonance anomalies. When they are modeled as finite imperfect periodic
      structures, it is time-consuming to calculate their optical properties precisely,
      and huge computational memories are needed to accommodate the large analytical
      domain. This limits the numerical performance, and so existing reports, which use
      the conventional boundary element method, refer to structures with less than 100
      periods. This paper shows that general optical properties and the impact of
      production error distributions can be calculated for guided-mode resonant grating
      filters with several hundred periods using the fast multipole boundary element
      method.

PMID- 20808398
TI  - Expansion of image interaction by the eigenfunction of the transmission cross
      coefficient to show the interaction between features.
AB  - This paper presents a method for evaluating the image interaction of two object
      patterns of arbitrary shape in partially coherent imaging. The interaction is
      shown to be the interference of the eigenfunctions of the transmission cross
      coefficient at the image plane convolved with each of the object patterns. For
      two arbitrary patterns, the ith eigenfunction convolved with one object pattern
      interferes only with the ith eigenfunction convolved with the second object
      pattern. This method is useful for understanding how object feature shapes
      influence image interactions, and examples are simulated to evaluate the method.
      A method to determine constructive and destructive interference areas is also
      introduced.

PMID- 20808399
TI  - Phase retrieval for superposed signals from multiple binary objects.
AB  - We introduce the binary superposed phase retrieval problem that aims at
      reconstructing multiple 0/1-valued functions with nonoverlapping bounded supports
      from moduli of superpositions of several displaced copies of their individual
      Fourier transforms. We discuss an application in coherent diffraction imaging of
      crystalline objects, propose two algorithms, and evaluate their performance by
      means of simulations.

PMID- 20808400
TI  - Influence of absorption on the anomalous negative refraction in right-handed
      uniaxial absorbing dielectric media.
AB  - In this work we study the anomalous negative refraction when a plane wave is
      incident from an isotropic medium to a uniaxial absorbing medium. We study the
      influence of the anisotropy on the refractive indices and the anisotropy on the
      absorption coefficients in the negative refraction of these materials. Negative
      refraction can occur for the ordinary and extraordinary waves for a wide range of
      values of the angle of incidence. The allowed values of the angle of incidence
      that lead to negative refraction are analyzed in detail as a function of the
      orientation of the optic axis and the values of the refractive indices and
      absorption coefficients.

PMID- 20808401
TI  - Polarization change induced by a galvanometric optical scanner.
AB  - We study the optical properties of a two-axis galvanometric optical scanner
      constituted by a pair of rotating planar mirrors, focusing our attention on the
      transformation induced on the polarization state of the input beam. We obtain the
      matrix that defines the transformation of the propagation direction of the beam
      and the Jones matrix that defines the transformation of the polarization state.
      Both matrices are expressed in terms of the rotation angles of two mirrors.
      Finally, we calculate the parameters of the general rotation in the Poincare
      sphere that describes the change in the polarization state for each mutual
      orientation of the mirrors.

PMID- 20808402
TI  - Exact space invariant illumination for partially coherent imaging systems.
AB  - What we believe to be a new illumination scheme that achieves space invariance
      and permits analytical determination of the image intensity distribution is
      proposed for partially coherent imaging systems. No additional lenses are needed
      for phase correction in front of the object and no restriction on illumination
      coherence is required. Conditions on the axial placement of the condenser with
      respect to the source and the object are specifically derived in terms of the
      condenser focal length and the distance from the object to the objective lens. By
      attaining space invariance, this new illumination scheme permits the use of
      transfer functions without approximation on illumination coherence. In addition,
      this illumination method establishes an exact Fourier transform relationship
      between the illumination and source mutual intensities, and thus significantly
      simplifies the analysis. Comparison with Kohler illumination is also presented.
      This apparatus is especially favorable for x-ray microscopy where lenses in this
      spectral region typically have a low efficiency.

PMID- 20808403
TI  - Maximum SNR pattern strategy for phase shifting methods in structured light
      illumination.
AB  - Structured light illumination by means of phase shifting patterns is a widely
      employed method for three-dimensional (3-D) image acquisition that is robust to
      ambient light and object albedo but may be especially susceptible to sensor and
      environment noise. In this paper, we study the specific technique of phase
      measuring profilometry (PMP) and the maximization of a pattern's signal to noise
      ratio (SNR). By treating the design of an N-pattern PMP process as placing points
      in an N-dimensional coding space, we define a pattern's SNR in terms of a pattern
      set's computational length and the number of coded phase periods in the projected
      patterns. Then, without introducing phase ambiguities, we propose a so-called
      edge pattern strategy that maximizes the computational length and number of
      periods. Theoretically, the edge pattern technique improves the SNR by 1.2381
      times when using three component patterns and by 15.5421 times when using five
      patterns. Experimental results further demonstrate the improved SNR of the
      proposed edge pattern technique such that more accurate 3-D results are achieved
      using fewer component patterns.

PMID- 20808404
TI  - Geometric interpretation of the Pancharatnam connection and non-cyclic
      polarization changes.
AB  - If the state of polarization of a monochromatic light beam is changed in a
      cyclical manner, the beam acquires-in addition to the usual dynamic phase-a
      geometric phase. This geometric or Pancharatnam-Berry phase equals half the solid
      angle of the contour traced out on the Poincare sphere. We show that such a
      geometric interpretation also exists for the Pancharatnam connection, the
      criterion according to which two beams with different polarization states are
      said to be in phase. This interpretation offers what is to our knowledge a new
      and intuitive method to calculate the geometric phase that accompanies non-cyclic
      polarization changes.

PMID- 20808405
TI  - Double-tailored nonimaging reflector optics for maximum-performance solar
      concentration.
AB  - A nonimaging strategy that tailors two mirror contours for concentration near the
      etendue limit is explored, prompted by solar applications where a sizable gap
      between the optic and absorber is required. Subtle limitations of this
      simultaneous multiple surface method approach are derived, rooted in the manner
      in which phase space boundaries can be tailored according to the edge-ray
      principle. The fundamental categories of double-tailored reflective optics are
      identified, only a minority of which can pragmatically offer maximum
      concentration at high collection efficiency. Illustrative examples confirm that
      acceptance half-angles as large as 30 mrad can be realized at a flux
      concentration of approximately 1000.

PMID- 20808406
TI  - Output irradiance of tapered lightpipes.
AB  - A light cone efficiently transports, distributes, and concentrates the incoming
      radiation. I derive a formula for the spatial irradiance (or illuminance)
      distribution at the exit aperture of a tapered light pipe. The theory is
      demonstrated by Monte Carlo ray-tracing for lightpipes with light-emitting diodes
      at the input face. The analysis is based on the addition of the radiation
      patterns of the multiple virtual sources that, as in a three-dimensional
      kaleidoscope, are seen through a tapered light tube. Given its explicit
      dependence on the structural and optical parameters, this analysis may be a
      useful tool in the development and application of light cones.

PMID- 20808407
TI  - Electromagnetic concentrators with arbitrary geometries based on Laplace's
      equation.
AB  - Concentrators with arbitrary geometries are designed based on the numerical
      solution of Laplace's equation, with which the material parameters can be
      independently obtained without any knowledge of the corresponding coordinate
      transformation. Results show that the concentrator designed using the numerical
      method has the same scattering and concentrating properties as that designed
      using the analytical method, except for a slight difference in the stretching
      region, which, however does not influence the design of the concentrator. The
      method developed in this paper is general and flexible for designing arbitrary
      concentrators. The validity of such a method and the concentrating effects are
      confirmed by full-wave simulations.

PMID- 20808408
TI  - Statistics of spatial derivatives of Stokes parameters for isotropic random
      polarization field.
AB  - The statistical properties of the spatial derivatives of the Stokes parameters
      for a random polarization field are studied. Based on the Gaussian assumption for
      the electric fields, the six-dimensional joint probability density function for
      the derivatives of the Stokes parameters is obtained from the statistics of the
      derivatives of the random polarization field. Subsequently, three two-dimensional
      probability density functions of derivatives of each Stokes parameter and the
      corresponding six marginal probability density functions are given. Finally, the
      joint and marginal density functions of the magnitude of the gradient of Stokes
      parameters are also derived for the first time, to our knowledge.

PMID- 20808409
TI  - Shifted-elementary-mode representation for partially coherent vectorial fields.
AB  - A representation of partially spatially coherent and partially polarized
      stationary electromagnetic fields is given in terms of mutually uncorrelated,
      transversely shifted, fully coherent, and polarized elementary electric-field
      modes. This representation allows one to propagate non-paraxial partially
      coherent vector fields using techniques for spatially fully coherent fields,
      which are numerically far more efficient than methods for propagating correlation
      functions. A procedure is given to determine the elementary modes from the
      radiant intensity and the far-zone polarization properties of the entire field.
      The method is applied to quasi-homogeneous fields with rotationally symmetric
      cos(n) theta radiant intensity distributions (theta being the diffraction angle
      with respect to the optical axis and n being an integer). This is an adequate
      model for fields emitted by, e.g., many light-emitting diodes.

PMID- 20808410
TI  - Method of determination of light-scatterer distribution in edge-lit backlight
      units using an analytical approach.
AB  - We present a method to find the optimum distribution of scatterers in an edge-lit
      lightguide plate (LGP) for rendering a uniform distribution of the outcoupled
      light. We propose a simple mathematical model describing the light propagation in
      a waveguide with a distribution of scattering elements located on the lower
      surface of the waveguide. We have found a differential equation giving the
      distribution of scattering elements leading to a uniform irradiance along the
      LGP, and we propose a method to determine the value of the outcoupling
      coefficient of an individual scattering element from the irradiance (or radiance)
      measurements. We have verified the validity of this model by performing ray
      tracing simulations on an LGP with the scattering elements distributed according
      to the solution of the proposed differential equation, and we have found a
      quantitative agreement between the analytical results and the simulated ones.
      Also this model has been used to directly calculate the output power of a given
      embossed LGP.

PMID- 20808411
TI  - Maximization of imaging resolution in optical wireless sensor/lab-on-chip/SoC
      networks with solar cells.
AB  - The availability of sophisticated and low-cost hardware on a single chip, for
      example, CMOS cameras, CPU, DSP, processors and communication transceivers,
      optics, microfluidics, and micromechanics, has fostered the development of system
      on-chip (SoC) technology, such as lab-on-chip or wireless multimedia sensor
      networks (WMSNs). WMSNs are networks of wirelessly interconnected devices on a
      chip that are able to ubiquitously retrieve multimedia content such as video from
      the environment and transfer it to a central location for additional processing.
      In this paper, we study WMSNs that include an optical wireless communication
      transceiver that uses light to transmit the information. One of the primary
      challenges in SoC design is to attain adequate resources like energy harvesting
      using solar cells in addition to imaging and communication capabilities, all
      within stringent spatial limitations while maximizing system performances. There
      is an inevitable trade-off between enhancing the imaging resolution and the
      expense of reducing communication capacity and energy harvesting capabilities, on
      one hand, and increasing the communication or the solar cell size to the
      detriment of the imaging resolution, on the other hand. We study these trade
      offs, derive a mathematical model to maximize the resolution of the imaging
      system, and present a numerical example that demonstrates maximum imaging
      resolution. Our results indicate that an eighth-order polynomial with only two
      constants provides the required area allocation between the different
      functionalities.

PMID- 20808412
TI  - Optimized design for realizing a large and uniform 2-D spot array.
AB  - In this paper we derive an optimal analytical solution for a phase only optical
      mask generating a two-dimensional (2-D) array of spots with uniform energy (i.e.,
      the integral over the shape of each spot). In previous methods the constraint
      while generating a 2-D array of spots was the uniformity in the peak value of
      each spot. In the presented approach the improved performance is obtained by
      applying mathematical optimization, while the constraints are set to have equal
      energetic content in each one of the spots.

PMID- 20808413
TI  - Generation of multiple spherical spots with a radially polarized beam in a 4pi
      focusing system.
AB  - We demonstrate the possibility of creating multiple spherical spots in a 4pi
      focusing system with a radially polarized beam. Using spherical waves to expand
      the plane wave factor in the Richards-Wolf integral, it is found that a proper
      spatial modulation in the amplitude of the input field with radial polarization
      can form multiple spherical spots with a focusing system satisfying the Herschel
      condition. These spots are distributed symmetrically about the focus on the
      optical axis with variable positions and intensities. Although we consider only
      the case of three spherical spots in this paper, generalization to the multiple
      spots case will present no difficulty.

PMID- 20808414
TI  - Minimum variance unbiased subpixel centroid estimation of point image limited by
      photon shot noise.
AB  - An unbiased subpixel centroid estimation algorithm of point image is proposed
      through the compensation of the systematic error of the center of mass method.
      The Cramer-Rao lower bound on centroid estimation variances is derived under the
      photon shot noise condition and is utilized to evaluate the proposed algorithm.
      Numerical analysis shows that the proposed centroid estimator attains the
      required lower bound; thus the proposed algorithm can be asserted as a minimum
      variance estimator. Simulation results indicate that the centroid accuracy is
      maximized when the Gaussian width of the signal spot is 0.2-0.3 pixel and the
      estimator can attain subpixel accuracy close to 1/100 pixel when 1000 photons are
      detected.

PMID- 20808415
TI  - Geometry of illumination, luminance contrast, and gloss perception.
AB  - The influence of both the geometry of illumination and luminance contrast on
      gloss perception has been examined using the method of paired comparison. Six
      achromatic glass samples having different lightness were illuminated by two light
      sources. Only one of these light sources was visible in reflection by the
      observer. By separate adjustment of the intensity of both light sources, the
      luminance of both the reflected image and the adjacent off-specular surroundings
      could be individually varied. It was found that visual gloss appraisal did not
      correlate with instrumentally measured specular gloss; however, psychometric
      contrast seemed to be a much better correlate. It has become clear that not only
      the sample surface characteristics determine gloss perception: the illumination
      geometry could be an even more important factor.

PMID- 20808416
TI  - Total transmission of incident plane waves that satisfy the Brewster conditions
      at a free-space-chiral interface.
AB  - The common definition of the Brewster angles for dielectric and magnetic achiral
      materials are the angles at which the vertically and horizontally polarized
      reflection coefficients vanish. We examine broader definitions of the Brewster
      conditions for waves that are incident on a free-space-chiral interface. Besides
      the common definition, the Brewster angles have been defined as the angles at
      which the polarizations of the reflected waves are independent of the
      polarizations of the incident waves. We consider total transmission of incident
      plane waves that satisfy the Brewster conditions at a free-space-chiral medium
      planar interface. In this case we determine the polarization of the incident wave
      for which the reflected vertically and horizontally polarized waves vanish
      simultaneously. Thus with this definition of the Brewster conditions the
      polarization of the reflected wave is undefined. The conditions for the
      excitation of surface waves are considered. The characteristic polarizations that
      are the same for the reflected and incident waves are also examined subject to
      the Brewster conditions. Potential applications of this analysis are to
      experimentally determine the chiral or geotropic measure of the medium and to
      identify and characterize biological and chemical materials through their optical
      activity in real time. Several independent measurements can be taken with the
      same polarimetric instrument to avoid false identifications. Since measurements
      can be conducted in the reflection mode they can be nonintrusive.

PMID- 20808417
TI  - Orbital motion of optically trapped particles in Laguerre-Gaussian beams.
AB  - A theoretical examination of off-axial trapping in non-paraxial Laguerre-Gaussian
      beams is presented for both the Rayleigh and Mie regimes. It is well known that
      the force acting on a particle may be divided into a term proportional to the
      intensity gradient and another representing the scattering force. The latter term
      may be further sub-divided into a dissipative radiation force and a term
      dependent on the electric field gradient. For Rayleigh particles in Laguerre
      Gaussian beams, it is shown that the field gradient term contributes exactly half
      of the scattering force. This may be compared with a plane wave, in which it
      makes zero contribution. The off-axis trapping positions for spheres with radii
      varying from 0.1 to 0.5 mum and a range of refractive indices are calculated
      numerically in the Mie regime, using a conjugate gradient approach. Azimuthal
      forces and orbital torques are presented for particles in their trapping
      positions, for beams with different orbital angular momentum and polarization
      states. The components of a "spin" torque, acting through the center of the
      particle, are also computed for absorbing particles in the Mie regime.

PMID- 20808418
TI  - Generation of hollow scalar and vector beams using a spot-defect mirror.
AB  - Generation of both scalar and vector hollow beams was demonstrated by using a
      mirror with a low-reflectivity spot to suppress the oscillation of lower order
      transverse modes. As scalar beams, several hollow Laguerre-Gaussian beams have
      been observed from a side-pumped Nd:yttrium aluminum garnet laser cavity. The
      intensity profiles were in an excellent agreement with theoretical ones. The
      phase front variation around the optical axis was verified to be spiral.
      Furthermore, both Laguerre-Gaussian and Bessel-Gaussian vector beams have been
      also observed from the identical cavity. In addition to the verification of
      intensity profiles, polarization pattern measurement confirmed that the beams had
      revolving polarization distributions along the azimuthal direction as
      theoretically predicted.

PMID- 20808419
TI  - Measurement of the absolute wavefront curvature radius in a heterodyne
      interferometer.
AB  - We present an analytical derivation of the coupling parameter relating the angle
      between two interfering beams in a heterodyne interferometer to the differential
      phase signals detected by a quadrant photodiode. This technique, also referred to
      as differential wavefront sensing, is commonly used in space-based gravitational
      wave detectors to determine the attitude of a test mass in one of the
      interferometer arms from the quadrant diode signals. Successive approximations to
      the analytical expression are made to simplify the investigation of parameter
      dependencies. Motivated by our findings, we propose what we believe to be a new
      measurement method to accurately determine the absolute wavefront curvature of a
      single measurement beam. We also investigate the change in the coupling parameter
      when the interferometer "test mirror" is moved from its nominal position, an
      effect which mediates the coupling of mirror displacement noise into differential
      phase measurements.

PMID- 20808421
TI  - Transmission of p- and s-polarized light through a prism and the condition of
      minimum deviation.
AB  - The condition of minimum deviation (MD) by a transparent optically isotropic
      prism is re-derived, and expressions for the intensity transmittances T(p)(theta)
      and T(s)(theta) of an uncoated prism of refractive index n and prism angle alpha
      for incident p- and s-polarized light and their derivatives with respect to the
      internal angle of refraction theta are obtained. When the MD condition
      (theta=alpha/2) is satisfied, T(s) is maximum and T(p) is maximum or minimum. The
      transmission ellipsometric parameters psi(t),Delta(t) of a symmetrically coated
      prism are also shown to be locally stationary with respect to theta at
      theta=alpha/2. The constraint on (n,alpha) for maximally flat transmittance (MFT)
      of p-polarized light at and near the MD condition is determined. The
      transmittance T(p) of prisms represented by points that lie below the locus
      (n,alpha) of MFT exhibits oscillation as a function of theta. No similar behavior
      is found for the s polarization. Magnitudes and angular positions of the maxima
      and minima of the oscillatory T(p)-versus-theta curves are also calculated as
      functions of alpha for a ZnS prism of refractive index n=2.35 in the visible.

PMID- 20808422
TI  - Paraxial theory of electromagnetic waves in plane inhomogeneous media.
AB  - The problem of electromagnetic waves propagating in inhomogeneous media is
      formulated within the paraxial approximation. The analysis is restricted to a
      medium with a plane and smooth inhomogeneity. The general form of a Gaussian beam
      is obtained in terms of the permittivity and permeability of the medium.
      Particular attention is paid to the case of internal reflection, where a short
      wavelength approximation breaks down; a possible treatment of the problem is
      proposed. A simple model is worked out to illustrate the formalism.

PMID- 20808423
TI  - Deb's Last Column, But Not Her Last Laugh.
AB  - In this humor column, a perinatal educator defines the term "rusty labor and
      delivery nurse" and passes the torch to a new generation of talented
      practitioners and columnists.

PMID- 20808424
TI  - Paternal fears of childbirth: a literature review.
AB  - To date, most studies on paternal childbirth fears have been exploratory or
      descriptive, conducted outside of the United States, and focused mainly on White,
      first-time fathers. Identified fears include harm to the mother or newborn,
      partner pain, feelings of helplessness, lack of knowledge, and fear of high-risk
      intervention. Fathers often report that childbirth classes are not helpful and,
      in some cases, even increase their fears. Some fathers view birth as traumatic,
      changing their perception of and relationship with their partner. Fathers also
      voice the need for more information and for reassurance that they are doing the
      right things for their partner during childbirth. This article summarizes the
      research findings on paternal childbirth fears and recommends topics for future
      study.

PMID- 20808425
TI  - Abuse in hospital-based birth settings?
AB  - Are laboring and birthing women treated abusively in the hospital? Although
      seldom recognized as abuse or violence against women, bullying and medical
      treatments under false pretenses, even in a hospital, constitute abuse and a
      basic human rights issue that needs attention. Naming the problem is a first
      step. The power of medical authority, the lack of accountability in the hospital
      hierarchical system, policies and protocols, and expectations of compliancy all
      make an environment ripe for abuse and present obstacles for both women and staff
      to recognize or stop abuse. Learning to recognize abuse and take effective
      action, and understanding the legal requirements for "informed consent" can help,
      but ending abuse will require systemic change.

PMID- 20808426
TI  - Persuasion: The Key to Changing Women's Ideas About Birth.
AB  - Although standard maternity care is not evidence-based and, in many cases,
      increases risks for mothers and babies, few women make birth decisions that
      reflect this knowledge. This column discusses persuasion as a way to change
      women's ideas about safe, healthy birth. The relationship between persuasion and
      choice is discussed, and the differences between presenting information and
      persuading women that natural birth is the safest and healthiest way to give
      birth are explored.

PMID- 20808427
TI  - Information giving and education in pregnancy: a review of qualitative studies.
AB  - Studies of childbirth education have universally failed to take into account the
      quality of the education provided to women and their families and whether its
      style of delivery meets women's preferences and needs. The present study sought
      to determine which educational approaches are most welcomed by women and most
      helpful to them in learning about labor, birth, and early parenting. A systematic
      survey of peer-reviewed studies on antenatal education, published in English from
      1996-2006 and which sought women's views and experiences, was conducted. Findings
      confirm women's preference for a small-group learning environment in which they
      can talk to each other as well as the educator and can relate information to
      their individual circumstances.

PMID- 20808428
TI  - A vaginal birth after cesarean, attended by a family member midwife serving as
      doula.
AB  - In this column, a mother and her doula describe the strategies used during
      pregnancy and labor to maximize the success of a vaginal birth after a previous
      cesarean surgery.

PMID- 20808429
TI  - New resources for childbirth educators and parents.
AB  - In this column, reviewers offer perspectives and comments on a variety of new
      media resources for childbirth educators and for expectant and new parents. The
      DVDs and books reviewed in this issue's column address the following topics:
      cultural views of labor and birth, as portrayed in the U.S. media; natural, safe,
      and healthy birth practices; memoirs of a midwife; a description of doula care to
      share with the children of expectant parents; baby behaviors; empowering women to
      choose the birth experience they want; making informed decisions about cesarean
      surgery; information and stories of hope for parents dealing with an infant in
      the neonatal intensive care unit; ways for parents to cope with perinatal or
      neonatal loss; and fathers' supportive role during the prenatal and postpartum
      periods.

PMID- 20808430
TI  - Environmental hazards education for childbirth educators.
AB  - The purpose of this article is to educate childbirth educators about
      environmental hazards and provide resources. Hazardous chemicals have been found
      in cord blood, placenta, meconium, and breastmilk samples. These chemicals
      include commonly known hazards such as lead, mercury, and environmental tobacco
      smoke, as well as some pesticides, solvents, products containing chlorine, and
      other chemicals referred to as "persistent organic pollutants." The fetus is
      particularly vulnerable to environmental chemicals that can disrupt the
      developmental process at critical times during gestation. Childbirth educators
      are encouraged to inform themselves in order to inform childbearing families to
      take preventive action and explore alternative behaviors to reduce exposure to
      environmental hazards.

PMID- 20808431
TI  - From psychoprophylactic to orgasmic birth.
AB  - The assumptions on which educators based childbirth education principles were
      valid when psychoprophylactic birth became available. Yet, educators and health
      care providers have changed their assumptions about birth as they have learned
      more from the midwifery model of care, how women want to give birth, and how
      capable the body is to give birth. Educators' teaching must now emphasize the
      synchrony of hormones that facilitates birth, the Sphincter Law, and the sharing
      of woman-to-woman stories throughout the generations if birth is to be set in its
      rightful place-in the hands of the mothers.

PMID- 20808432
TI  - Thyroid hormone may regulate mRNA abundance in liver by acting on microRNAs.
AB  - MicroRNAs (miRNAs) are extensively involved in diverse biological processes.
      However, very little is known about the role of miRNAs in mediating the action of
      thyroid hormones (TH). Appropriate TH levels are known to be critically important
      for development, differentiation and maintenance of metabolic balance in mammals.
      We induced transient hypothyroidism in juvenile mice by short-term exposure to
      methimazole and perchlorate from post natal day (PND) 12 to 15. The expression of
      miRNAs in the liver was analyzed using Taqman Low Density Arrays (containing up
      to 600 rodent miRNAs). We found the expression of 40 miRNAs was significantly
      altered in the livers of hypothyroid mice compared to euthyroid controls. Among
      the miRNAs, miRs-1, 206, 133a and 133b exhibited a massive increase in expression
      (50- to 500-fold). The regulation of TH on the expression of miRs-1, 206, 133a
      and 133b was confirmed in various mouse models including: chronic hypothyroid,
      short-term hyperthyroid and short-term hypothyroid followed by TH
      supplementation. TH regulation of these miRNAs was also confirmed in mouse
      hepatocyte AML 12 cells. The expression of precursors of miRs-1, 206, 133a and
      133b were examined in AML 12 cells and shown to decrease after TH treatment, only
      pre-mir-206 and pre-mir-133b reached statistical significance. To identify the
      targets of these miRNAs, DNA microarrays were used to examine hepatic mRNA levels
      in the short-term hypothyroid mouse model relative to controls. We found
      transcripts from 92 known genes were significantly altered in these hypothyroid
      mice. Web-based target predication software (TargetScan and Microcosm) identified
      14 of these transcripts as targets of miRs-1, 206, 133a and 133b. The vast
      majority of these mRNA targets were significantly down-regulated in hypothyroid
      mice, corresponding with the up-regulation of miRs-1, 206, 133a and 133b in
      hypothyroid mouse liver. To further investigate target genes, miR-206 was over
      expressed in AML 12 cells. TH treatment of cells over-expressing miR-206 resulted
      in decreased miR-206 expression, and a significant increase in two predicted
      target genes, Mup1 and Gpd2. The results suggest that TH regulation of these
      genes may occur secondarily via miR-206. These studies provide new insight into
      the role of miRNAs in mediating TH regulation of gene expression.

PMID- 20808433
TI  - Associations of variants in CHRNA5/A3/B4 gene cluster with smoking behaviors in a
      Korean population.
AB  - Multiple genome-wide and targeted association studies reveal a significant
      association of variants in the CHRNA5-CHRNA3-CHRNB4 (CHRNA5/A3/B4) gene cluster
      on chromosome 15 with nicotine dependence. The subjects examined in most of these
      studies had a European origin. However, considering the distinct linkage
      disequilibrium patterns in European and other ethnic populations, it would be of
      tremendous interest to determine whether such associations could be replicated in
      populations of other ethnicities, such as Asians. In this study, we performed
      comprehensive association and interaction analyses for 32 single-nucleotide
      polymorphisms (SNPs) in CHRNA5/A3/B4 with smoking initiation (SI), smoking
      quantity (SQ), and smoking cessation (SC) in a Korean sample (N = 8,842). We
      found nominally significant associations of 7 SNPs with at least one smoking
      related phenotype in the total sample (SI: P = 0.015 approximately 0.023; SQ: P =
      0.008 approximately 0.028; SC: P = 0.018 approximately 0.047) and the male sample
      (SI: P = 0.001 approximately 0.023; SQ: P = 0.001 approximately 0.046; SC: P =
      0.01). A spectrum of haplotypes formed by three consecutive SNPs located between
      rs16969948 in CHRNA5 and rs6495316 in the intergenic region downstream from the
      5' end of CHRNB4 was associated with these three smoking-related phenotypes in
      both the total and the male sample. Notably, associations of these variants and
      haplotypes with SC appear to be much weaker than those with SI and SQ. In
      addition, we performed an interaction analysis of SNPs within the cluster using
      the generalized multifactor dimensionality reduction method and found a
      significant interaction of SNPs rs7163730 in LOC123688, rs6495308 in CHRNA3, and
      rs7166158, rs8043123, and rs11072793 in the intergenic region downstream from the
      5' end of CHRNB4 to be influencing SI in the male sample. Considering that fewer
      than 5% of the female participants were smokers, we did not perform any analysis
      on female subjects specifically. Together, our detected associations of variants
      in the CHRNA5/A3/B4 cluster with SI, SQ, and SC in the Korean smoker samples
      provide strong evidence for the contribution of this cluster to the etiology of
      SI, ND, and SC in this Asian population.

PMID- 20808434
TI  - Optimized hydrophobic interactions and hydrogen bonding at the target-ligand
      interface leads the pathways of drug-designing.
AB  - BACKGROUND: Weak intermolecular interactions such as hydrogen bonding and
      hydrophobic interactions are key players in stabilizing energetically-favored
      ligands, in an open conformational environment of protein structures. However, it
      is still poorly understood how the binding parameters associated with these
      interactions facilitate a drug-lead to recognize a specific target and improve
      drugs efficacy. To understand this, comprehensive analysis of hydrophobic
      interactions, hydrogen bonding and binding affinity have been analyzed at the
      interface of c-Src and c-Abl kinases and 4-amino substituted 1H-pyrazolo [3, 4-d]
      pyrimidine compounds. METHODOLOGY: In-silico docking studies were performed,
      using Discovery Studio software modules LigandFit, CDOCKER and ZDOCK, to
      investigate the role of ligand binding affinity at the hydrophobic pocket of c
      Src and c-Abl kinase. Hydrophobic and hydrogen bonding interactions of docked
      molecules were compared using LigPlot program. Furthermore, 3D-QSAR and MFA
      calculations were scrutinized to quantify the role of weak interactions in
      binding affinity and drug efficacy. CONCLUSIONS: The in-silico method has enabled
      us to reveal that a multi-targeted small molecule binds with low affinity to its
      respective targets. But its binding affinity can be altered by integrating the
      conformationally favored functional groups at the active site of the ligand
      target interface. Docking studies of 4-amino-substituted molecules at the
      bioactive cascade of the c-Src and c-Abl have concluded that 3D structural
      folding at the protein-ligand groove is also a hallmark for molecular recognition
      of multi-targeted compounds and for predicting their biological activity. The
      results presented here demonstrate that hydrogen bonding and optimized
      hydrophobic interactions both stabilize the ligands at the target site, and help
      alter binding affinity and drug efficacy.

PMID- 20808435
TI  - The cytoplasmic location of chicken mx is not the determining factor for its lack
      of antiviral activity.
AB  - BACKGROUND: Chicken Mx belongs to the Mx family of interferon-induced dynamin
      like GTPases, which in some species possess potent antiviral properties.
      Conflicting data exist for the antiviral capability of chicken Mx. Reports of
      anti-influenza activity of alleles encoding an Asn631 polymorphism have not been
      supported by subsequent studies. The normal cytoplasmic localisation of chicken
      Mx may influence its antiviral capacity. Here we report further studies to
      determine the antiviral potential of chicken Mx against Newcastle disease virus
      (NDV), an economically important cytoplasmic RNA virus of chickens, and Thogoto
      virus, an orthomyxovirus known to be exquisitely sensitive to the cytoplasmic MxA
      protein from humans. We also report the consequences of re-locating chicken Mx to
      the nucleus. METHODOLOGY/PRINCIPAL FINDINGS: Chicken Mx was tested in virus
      infection assays using NDV. Neither the Asn631 nor Ser631 Mx alleles (when
      transfected into 293T cells) showed inhibition of virus-directed gene expression
      when the cells were subsequently infected with NDV. Human MxA however did show
      significant inhibition of NDV-directed gene expression. Chicken Mx failed to
      inhibit a Thogoto virus (THOV) minireplicon system in which the cytoplasmic human
      MxA protein showed potent and specific inhibition. Relocalisation of chicken Mx
      to the nucleus was achieved by inserting the Simian Virus 40 large T antigen
      nuclear localisation sequence (SV40 NLS) at the N-terminus of chicken Mx. Nuclear
      re-localised chicken Mx did not inhibit influenza (A/PR/8/34) gene expression
      during virus infection in cell culture or influenza polymerase activity in
      A/PR/8/34 or A/Turkey/50-92/91 minireplicon systems. CONCLUSIONS/SIGNIFICANCE:
      The chicken Mx protein (Asn631) lacks inhibitory effects against THOV and NDV,
      and is unable to suppress influenza replication when artificially re-localised to
      the cell nucleus. Thus, the natural cytoplasmic localisation of the chicken Mx
      protein does not account for its lack of antiviral activity.

PMID- 20808437
TI  - What currency do bumble bees maximize?
AB  - In modelling bumble bee foraging, net rate of energetic intake has been suggested
      as the appropriate currency. The foraging behaviour of honey bees is better
      predicted by using efficiency, the ratio of energetic gain to expenditure, as the
      currency. We re-analyse several studies of bumble bee foraging and show that
      efficiency is as good a currency as net rate in terms of predicting behaviour. We
      suggest that future studies of the foraging of bumble bees should be designed to
      distinguish between net rate and efficiency maximizing behaviour in an attempt to
      discover which is the more appropriate currency.

PMID- 20808436
TI  - NMDA receptors on non-dopaminergic neurons in the VTA support cocaine
      sensitization.
AB  - BACKGROUND: The initiation of behavioral sensitization to cocaine and other
      psychomotor stimulants is thought to reflect N-methyl-D-aspartate receptor
      (NMDAR)-mediated synaptic plasticity in the mesolimbic dopamine (DA) circuitry.
      The importance of drug induced NMDAR mediated adaptations in ventral tegmental
      area (VTA) DA neurons, and its association with drug seeking behaviors, has
      recently been evaluated in Cre-loxp mice lacking functional NMDARs in DA neurons
      expressing Cre recombinase under the control of the endogenous dopamine
      transporter gene (NR1(DATCre) mice). METHODOLOGY AND PRINCIPAL FINDINGS: Using an
      additional NR1(DATCre) mouse transgenic model, we demonstrate that while the
      selective inactivation of NMDARs in DA neurons eliminates the induction of
      molecular changes leading to synaptic strengthening, behavioral measures such as
      cocaine induced locomotor sensitization and conditioned place preference remain
      intact in NR1(DATCre) mice. Since VTA DA neurons projecting to the prefrontal
      cortex and amygdala express little or no detectable levels of the dopamine
      transporter, it has been speculated that NMDA receptors in DA neurons projecting
      to these brain areas may have been spared in NR1(DATCre) mice. Here we
      demonstrate that the NMDA receptor gene is ablated in the majority of VTA DA
      neurons, including those exhibiting undetectable DAT expression levels in our
      NR1(DATCre) transgenic model, and that application of an NMDAR antagonist within
      the VTA of NR1(DATCre) animals still blocks sensitization to cocaine.
      CONCLUSIONS/SIGNIFICANCE: These results eliminate the possibility of NMDAR
      mediated neuroplasticity in the different DA neuronal subpopulations in our
      NR1(DATCre) mouse model and therefore suggest that NMDARs on non-DA neurons
      within the VTA must play a major role in cocaine-related addictive behavior.

PMID- 20808438
TI  - What noseleaves do for FM bats depends on their degree of sensorial
      specialization.
AB  - BACKGROUND: Many bats vocalizing through their nose carry a prominent noseleaf
      that is involved in shaping the emission beam of these animals. To our knowledge,
      the exact role of these appendages has not been thoroughly investigated as for no
      single species both the hearing and the emission spatial sensitivities have been
      obtained. In this paper, we set out to evaluate the complete spatial sensitivity
      of two species of New World leaf-nosed bats: Micronycteris microtis and
      Phyllostomus discolor. From an ecological point of view, these species are
      interesting as they belong to the same family (Phyllostomidae) and their
      noseleaves are morphologically similar. They differ vastly in the niche they
      occupy. Comparing these species allows us to relate differences in function of
      the noseleaf to the ecological background of bat species. METHODOLOGY/PRINCIPAL
      FINDINGS: We simulate the spatial sensitivity of both the hearing and the
      emission subsystems of two species, M. microtis and P. discolor. This technique
      allows us to evaluate the respective roles played by the noseleaf in the
      echolocation system of these species. We find that the noseleaf of M. microtis
      focuses the radiated energy better and yields better control over the emission
      beam. CONCLUSIONS: From the evidence presented we conclude that the noseleaves
      serve quantitatively different functions for different bats. The main function of
      the noseleaf is to serve as an energy focusing mechanism that increases the
      difference between the reflected energy from objects in the focal area and
      objects in the periphery. However, despite the gross morphological similarities
      between the noseleaves of the two Phyllostomid species they focus the energy to a
      different extent, a capability that can be linked to the different ecological
      niches occupied by the two species.

PMID- 20808439
TI  - Trigonometric regressive spectral analysis reliably maps dynamic changes in
      baroreflex sensitivity and autonomic tone: the effect of gender and age.
AB  - BACKGROUND: The assessment of baroreflex sensitivity (BRS) has emerged as
      prognostic tool in cardiology. Although available computer-assisted methods,
      measuring spontaneous fluctuations of heart rate and blood pressure in the time
      and frequency domain are easily applicable, they do not allow for quantification
      of BRS during cardiovascular adaption processes. This, however, seems an
      essential criterion for clinical application. We evaluated a novel algorithm
      based on trigonometric regression regarding its ability to map dynamic changes in
      BRS and autonomic tone during cardiovascular provocation in relation to gender
      and age. METHODOLOGY/PRINCIPAL FINDINGS: We continuously recorded systemic
      arterial pressure, electrocardiogram and respiration in 23 young subjects (25+/-2
      years) and 22 middle-aged subjects (56+/-4 years) during cardiovascular autonomic
      testing (metronomic breathing, Valsalva manoeuvre, head-up tilt). Baroreflex- and
      spectral analysis was performed using the algorithm of trigonometric regressive
      spectral analysis. There was an age-related decline in spontaneous BRS and high
      frequency oscillations of RR intervals. Changes in autonomic tone evoked by
      cardiovascular provocation were observed as shifts in the ratio of low to high
      frequency oscillations of RR intervals and blood pressure. Respiration at 0.1 Hz
      elicited an increase in BRS while head-up tilt and Valsalva manoeuvre resulted in
      a downregulation of BRS. The extent of autonomic adaption was in general more
      pronounced in young individuals and declined stronger with age in women than in
      men. CONCLUSIONS/SIGNIFICANCE: The trigonometric regressive spectral analysis
      reliably maps age- and gender-related differences in baroreflex- and autonomic
      function and is able to describe adaption processes of baroreceptor circuit
      during cardiovascular stimulation. Hence, this novel algorithm may be a useful
      screening tool to detect abnormalities in cardiovascular adaption processes even
      when resting values appear to be normal.

PMID- 20808440
TI  - Differential regulation of the variations induced by environmental richness in
      adult neurogenesis as a function of time: a dual birthdating analysis.
AB  - Adult hippocampal neurogenesis (AHN) augments after environmental enrichment (EE)
      and it has been related to some of the anxiolytic, antidepressant and
      neuroprotective effects of EE. Indeed, it has been suggested that EE specifically
      modulates hippocampal neurogenic cell populations over the course of time. Here
      we have used dual-birthdating to study two subpopulations of newborn neuron in
      mice (Mus musculus): those born at the beginning and at the end of enrichment. In
      this way, we demonstrate that while short-term cell survival is upregulated after
      an initial 1 week period of enrichment in 2 month old female mice, after long
      term enrichment (2 months) neither cell proliferation nor the survival of the
      younger newly born cell populations are distinguishable from that observed in non
      enriched control mice. In addition, we show that the survival of older newborn
      neurons alone (i.e. those born at the beginning of the enrichment) is higher than
      in controls, due to the significantly lower levels of cell death. Indeed, these
      parameters are rapidly adjusted to the sudden cessation of the EE conditions.
      These findings suggest both an early selective, long-lasting effect of EE on the
      neurons born in the initial stages of enrichment, and a quick response when the
      environment again becomes impoverished. Therefore, EE induces differential
      effects on distinct subpopulations of newborn neurons depending on the age of the
      immature cells and on the duration of the EE itself. The interaction of these two
      parameters constitutes a new, specific regulation of these neurogenic populations
      that might account for the long-term enrichment's behavioral effects.

PMID- 20808441
TI  - TRPA1 mediates mechanical currents in the plasma membrane of mouse sensory
      neurons.
AB  - Mechanosensitive channels serve as essential sensors for cells to interact with
      their environment. The identity of mechanosensitive channels that underlie
      somatosensory touch transduction is still a mystery. One promising
      mechanotransduction candidate is the Transient Receptor Potential Ankyrin 1
      (TRPA1) ion channel. To determine the role of TRPA1 in the generation of
      mechanically-sensitive currents, we used dorsal root ganglion (DRG) neuron
      cultures from adult mice and applied rapid focal mechanical stimulation
      (indentation) to the soma membrane. Small neurons (diameter <27 microm) were
      studied because TRPA1 is functionally present in these neurons which largely give
      rise to C-fiber afferents in vivo. Small neurons were classified by isolectin B4
      binding. Mechanically-activated inward currents were classified into two
      subtypes: Slowly Adapting and Transient. First, significantly more IB4 negative
      neurons (84%) responded to mechanical stimulation than IB4 positive neurons
      (54%). Second, 89% of Slowly Adapting currents were present in IB4 negative
      neurons whereas only 11% were found in IB4 positive neurons. Third, Slowly
      Adapting currents were completely absent in IB4 negative neurons from TRPA1-/-
      mice. Consistent with this, Slowly Adapting currents were abolished in wild type
      IB4 negative neurons stimulated in the presence of a TRPA1 antagonist, HC-030031.
      In addition, the amplitude of Transient mechanically-activated currents in IB4
      positive neurons from TRPA1-/- mice was reduced by over 60% compared to TRPA1+/+
      controls; however, a similar reduction did not occur in wild-type neurons treated
      with HC-030031. Transfection of TRPA1 in HEK293 cells did not significantly alter
      the proportion or magnitude of mechanically-activated currents in HEK293 cells,
      indicating that TRPA1 alone is not sufficient to confer mechanical
      sensitivity.These parallel genetic and pharmacological data demonstrate that
      TRPA1 mediates the Slowly Adapting mechanically-activated currents in small
      diameter IB4 negative neurons from adult mice. The TRPA1 protein may also
      contribute to a complex that mediates Transient mechanically-activated currents
      in small IB4 positive C fiber type neurons.

PMID- 20808442
TI  - Projected loss of a salamander diversity hotspot as a consequence of projected
      global climate change.
AB  - BACKGROUND: Significant shifts in climate are considered a threat to plants and
      animals with significant physiological limitations and limited dispersal
      abilities. The southern Appalachian Mountains are a global hotspot for
      plethodontid salamander diversity. Plethodontids are lungless ectotherms, so
      their ecology is strongly governed by temperature and precipitation. Many
      plethodontid species in southern Appalachia exist in high elevation habitats that
      may be at or near their thermal maxima, and may also have limited dispersal
      abilities across warmer valley bottoms. METHODOLOGY/PRINCIPAL FINDINGS: We used a
      maximum-entropy approach (program Maxent) to model the suitable climatic habitat
      of 41 plethodontid salamander species inhabiting the Appalachian Highlands region
      (33 individual species and eight species included within two species complexes).
      We evaluated the relative change in suitable climatic habitat for these species
      in the Appalachian Highlands from the current climate to the years 2020, 2050,
      and 2080, using both the HADCM3 and the CGCM3 models, each under low and high
      CO(2) scenarios, and using two-model thresholds levels (relative suitability
      thresholds for determining suitable/unsuitable range), for a total of 8 scenarios
      per species. CONCLUSION/SIGNIFICANCE: While models differed slightly, every
      scenario projected significant declines in suitable habitat within the
      Appalachian Highlands as early as 2020. Species with more southern ranges and
      with smaller ranges had larger projected habitat loss. Despite significant
      differences in projected precipitation changes to the region, projections did not
      differ significantly between global circulation models. CO(2) emissions scenario
      and model threshold had small effects on projected habitat loss by 2020, but did
      not affect longer-term projections. Results of this study indicate that choice of
      model threshold and CO(2) emissions scenario affect short-term projected shifts
      in climatic distributions of species; however, these factors and choice of global
      circulation model have relatively small affects on what is significant projected
      loss of habitat for many salamander species that currently occupy the Appalachian
      Highlands.

PMID- 20808443
TI  - Analysis of death receptor 5 and caspase-8 expression in primary and metastatic
      head and neck squamous cell carcinoma and their prognostic impact.
AB  - Death receptor 5 (DR5) and caspase-8 are major components in the extrinsic
      apoptotic pathway. The alterations of the expression of these proteins during the
      metastasis of head and neck squamous cell carcinoma (HNSCC) and their prognostic
      impact have not been reported. The present study analyzes the expression of DR5
      and caspase-8 by immunohistochemistry (IHC) in primary and metastatic HNSCCs and
      their impact on patient survival. Tumor samples in this study included 100
      primary HNSCC with no evidence of metastasis, 100 primary HNSCC with lymph node
      metastasis (LNM) and 100 matching LNM. IHC analysis revealed a significant loss
      or downregulation of DR5 expression in primary tumors with metastasis and their
      matching LNM compared to primary tumors with no evidence of metastasis. A similar
      trend was observed in caspase-8 expression although it was not statistically
      significant. Downregulation of caspase-8 and DR5 expression was significantly
      correlated with poorly differentiated tumors compared to moderately and well
      differentiated tumors. Univariate analysis indicates that, in HNSCC with no
      metastasis, higher expression of caspase-8 significantly correlated with better
      disease-free survival and overall survival. However, in HNSCC with LNM, higher
      caspase-8 expression significantly correlated with poorer disease-free survival
      and overall survival. Similar results were also generated when we combined both
      DR5 and caspase-8. Taken together, we suggest that both DR5 and caspase-8 are
      involved in regulation of HNSCC metastasis. Our findings warrant further
      investigation on the dual role of caspase-8 in cancer development.

PMID- 20808444
TI  - VE-statin/egfl7 expression in endothelial cells is regulated by a distal enhancer
      and a proximal promoter under the direct control of Erg and GATA-2.
AB  - Angiogenesis is the process by which new blood vessels arise from existing ones
      by the budding out of endothelial cell capillaries from the luminal side of blood
      vessels. Blood vessel formation is essential for organ development during
      embryogenesis and is associated with several physiological and pathological
      processes, such as wound healing and tumor development. The VE-statin/egfl7 gene
      is specifically expressed in endothelial cells during embryonic development and
      in the adult. We studied here the regulatory mechanisms that control this tissue
      specific expression. RT-qPCR analyses showed that the specificity of expression
      of VE-statin/egfl7 in endothelial cells is not shared with its closest neighbor
      genes notch1 and agpat2 on the mouse chromosome 2. Chromatin-immunoprecipitation
      analysis of histone modifications at the VE-statin/egfl7 locus showed that the
      chromatin is specifically opened in endothelial cells, but not in fibroblasts at
      the transcription start sites. A 13 kb genomic fragment of promoter was cloned
      and analyzed by gene reporter assays which showed that two conserved regions are
      important for the specific expression of VE-statin/egfl7 in endothelial cells; a 
      8409/-7563 enhancer and the -252/+38 region encompassing the exon-1b
      transcription start site. The latter contains essential GATA and ETS-binding
      sites, as assessed by linker-scanning analysis and site-directed mutagenesis. An
      analysis of expression of the ETS and GATA transcription factors showed that Erg,
      Fli-1 and GATA-2 are the most highly expressed factors in endothelial cells. Erg
      and GATA-2 directly control the expression of the endogenous VE-statin/egfl7
      while Fli-1 probably exerts an indirect control, as assessed by RNA interference
      and chromatin immunoprecipitation. This first detailed analysis of the mechanisms
      that govern the expression of the VE-statin/egfl7 gene in endothelial cells
      pinpoints the specific importance of ETS and GATA factors in the specific
      regulation of genes in this cell lineage.

PMID- 20808446
TI  - Erratum: Case Report of Spontaneous, Nonspinal Fractures in a Multiple Myeloma
      Patient on Long-term Pamidronate and Zoledronic Acid.
AB  - [This corrects the article DOI: 10.1007/s11420-008-9077-4.].

PMID- 20808448
TI  - Human granulocytic anaplasmosis: First reported case in Canada.
AB  - Human granulocytic anaplasmosis (HGA) is a tick-borne rickettsial infection of
      peripheral blood neutrophils caused by Anaplasma phagocytophilum. While this
      infection is increasingly recognized as endemic throughout much of the United
      States, no Canadian cases have been previously described, despite the agent being
      identified in Canadian ticks. Herein we present a case of HGA acquired in an
      urban Alberta centre. Canadian physicians must be aware of the possibility of
      tick-borne rickettsial diseases as etiology of fever in individuals presenting
      with leukopenia/lymphopenia, thrombocytopenia and elevated transaminases during
      periods of tick activity. Prompt recognition and treatment are important in
      minimizing resultant morbidity and mortality.

PMID- 20808445
TI  - Genome-wide gene expression analysis in response to organophosphorus pesticide
      chlorpyrifos and diazinon in C. elegans.
AB  - Organophosphorus pesticides (OPs) were originally designed to affect the nervous
      system by inhibiting the enzyme acetylcholinesterase, an important regulator of
      the neurotransmitter acetylcholine. Over the past years evidence is mounting that
      these compounds affect many other processes. Little is known, however, about gene
      expression responses against OPs in the nematode Caenorhabditis elegans. This is
      surprising because C. elegans is extensively used as a model species in toxicity
      studies. To address this question we performed a microarray study in C. elegans
      which was exposed for 72 hrs to two widely used Ops, chlorpyrifos and diazinon,
      and a low dose mixture of these two compounds. Our analysis revealed
      transcriptional responses related to detoxification, stress, innate immunity, and
      transport and metabolism of lipids in all treatments. We found that for both
      compounds as well as in the mixture, these processes were regulated by different
      gene transcripts. Our results illustrate intense, and unexpected crosstalk
      between gene pathways in response to chlorpyrifos and diazinon in C. elegans.

PMID- 20808449
TI  - Nocardia farcinica lung abscess presenting in the context of advanced HIV
      infection: Spontaneous resolution in response to highly active antiretroviral
      therapy alone.
AB  - A 43-year-old man, known to be HIV-positive, presented with a six-week history of
      symptoms including cough, hemoptysis, anterior chest pain, fever and wasting. His
      CD4 cell count was 46 cells/muL, and his chest x-ray showed a cavitating lesion
      in the left upper lobe. Sputum culture was positive for Nocardia farcinica. His
      infection resolved following initiation of antiretroviral therapy. Nocardia is an
      uncommon opportunistic pathogen in patients with HIV infection and is usually
      associated with advanced CD4 depletion, cavitary pneumonia, metastatic infection
      and high mortality. The impact of antiretroviral therapy on Nocardia infection in
      the setting of HIV has not been clearly elucidated. The current report is the
      first to present a case in which a complete clinical cure of Nocardia pneumonia
      has been documented, primarily in response to highly active antiretroviral
      therapy alone.

PMID- 20808450
TI  - Pyogenic ventriculitis complicating Aggregatibacter aphrophilus infective
      endocarditis: A case report and literature review.
AB  - Pyogenic ventriculitis (PV) is an uncommon, but frequently fatal infection that
      results from inflammation of the ventricular ependymal lining associated with a
      purulent ventricular system. PV has been rarely reported as a secondary
      complication of infective endocarditis. Prompt diagnosis and treatment with
      appropriate culture-directed antibiotics with adequate central nervous system
      penetration is crucial when managing patients who are suspected of having PV. The
      present study reports on a fatal case of a previously well 42-year-old alcoholic
      woman with infective endocarditis caused by Aggregatibacter aphrophilus, with
      secondary brain abscess and spontaneous rupture into the ventricles causing PV.

PMID- 20808451
TI  - Fever and purpuric lesions in a preschool child.

PMID- 20808452
TI  - Cytomegalovirus colitis in an HIV-positive woman with a relatively preserved CD4
      count.

PMID- 20808453
TI  - Genetically typed community-acquired methicillin-resistant Staphylococcus aureus
      in a Canadian hospital.

PMID- 20808454
TI  - Evaluation of tumour necrosis factor-alpha and interleukin-1beta in an
      experimental pyelonephritis model induced with planktonic and biofilms cells of
      Pseudomonas aeruginosa.
AB  - Urinary tract infections may induce severe inflammation, transient impairment in
      renal function and scar formation, ranging in severity from acute symptomatic
      pyelonephritis to chronic pyelonephritis, and have the potential to lead to renal
      failure and death. In the present study, the relationship between production of
      tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta),
      neutrophil recruitment, bacterial colonization and tissue damage was investigated
      using a mouse model of acute ascending pyelonephritis induced with planktonic and
      biofilm cells of Pseudomonas aeruginosa. Neutrophil influx correlated with rise
      in TNF-alpha and IL-1beta, indicating an association between these cytokines and
      neutrophil infiltration. However, biofilm cells of P aeruginosa induced higher
      levels of TNF-alpha and IL-1beta leading to higher neutrophil infiltration
      causing tissue damage, assessed in terms of malondialdehyde, lactate
      dehydrogenase and glutathione content, which may have contributed to bacterial
      persistence compared with their planktonic counterparts. The results of the
      present investigation suggest that exaggerated cytokine production during P
      aeruginosa-induced pyelonephritis causes tissue damage operative through
      neutrophil recruitment leading to bacterial persistence in host tissues. The
      findings of the present study may be relevant for the better understanding of
      disease pathophysiology and for the future developments of preventive strategies
      against pyelonephritis based on anti-inflammatory intervention.

PMID- 20808455
TI  - Risk factors for and outcomes associated with clinical isolates of Escherichia
      coli and Klebsiella species resistant to extended-spectrum cephalosporins among
      patients admitted to Canadian hospitals.
AB  - BACKGROUND: Clinical features associated with Gram-negative bacterial isolates
      with extended-spectrum beta-lactamase (ESBL)- and AmpC-mediated resistance
      identified in Canadian hospitals is largely unknown. The objective of the present
      study was to determine the demographics, risk factors and outcomes of patients
      with ESBL- or AmpC-mediated resistant organisms in Canadian hospitals. METHODS:
      Patients with clinical cultures of Escherichia coli or Klebsiella species were
      matched with patients with a similar organism but susceptible to third-generation
      cephalosporins. Molecular identification of the AmpC or ESBL was determined using
      a combination of polymerase chain reaction and sequence analysis. Univariate and
      multivariate logistic regression analysis was performed to identify variables
      associated with becoming a case. RESULTS: Eight Canadian hospitals identified 106
      cases (ESBL/AmpC) and 106 controls. All risk factors identified in the univariate
      analysis as a predictor of being an ESBL/AmpC cases at the 0.20 P-value were
      included in the multivariate analysis. No significant differences in outcomes
      were observed (unfavourable responses 17% versus 15% and mortality rates 13%
      versus 7%, P not significant). Multivariate logistic regression found an
      association of becoming an ESBL/AmpC case with: previous admission to a nursing
      home (OR 8.28, P=0.01) or acute care facility (OR 1.96, P=0.03), length of stay
      before infection (OR 3.05, P=0.004), and previous use of first-generation
      cephalosporins (OR 2.38, P=0.02) or third-generation cephalosporins (OR 4.52,
      P=0.01). Appropriate antibiotics were more likely to be given to controls (27.0%
      versus 13.3%, P=0.05) and number of days to appropriate antibiotics was longer
      for cases (median 2.8 days versus 1.2 days, P=0.05). CONCLUSION: The importance
      of patient medical history, present admission and antibiotic use should be
      considered for all E coli or Klebsiella species patients pending susceptibility
      testing results.

PMID- 20808456
TI  - A double-blind, randomized, controlled trial of topical polysporin triple
      compound versus topical mupirocin for the eradication of colonization with
      methicillin-resistant Staphylococcus aureus in a complex continuing care
      population.
AB  - BACKGROUND: Intranasal mupirocin or Polysporin Triple (PT) ointment (polymyxin B,
      bacitracin, gramicidin), in combination with chlorhexidine body washes, have been
      used for eradicating methicillin-resistant Staphylococcus aureus (MRSA), but no
      comparative studies have been done. METHODS: A double-blind, randomized,
      controlled clinical trial to compare the efficacy of mupirocin versus PT ointment
      in combination with chlorhexidine body washes in eradicating MRSA carriage was
      conducted. Asymptomatic MRSA carriers, medically stable and at least 18 years of
      age who were patients on medical wards, received twice daily application of
      either mupirocin or PT ointment to the anterior nares plus once daily 2%
      chlorhexidine body washes for seven days. Follow-up swabs from multiple sites
      using broth enrichment were conducted at 48 h, and one, two, four, eight and 12
      weeks. RESULTS: Of 103 patients eligible for analysis (54 mupirocin; 49 PT), no
      significant differences between the two groups with respect to baseline
      demographics, risk factors for MRSA or MRSA colonization sites were noted. At 48
      h, 35 of 54 (65%) patients in the mupirocin group versus 15 of 49 (31%) in the PT
      group (P=0.001) were found to be MRSA negative at all sites. Significant
      differences were observed at one and two weeks but were not maintained at other
      intervals. In those with complete microbiological follow-up, MRSA eradication at
      all sites occurred in 12 of 39 (30.8%) mupirocin- and one of 36 (2.8%) PT-treated
      patients (P=0.001). CONCLUSION: Both agents demonstrated poor efficacy and PT was
      significantly less efficacious than mupirocin at 12 weeks in eradicating MRSA
      from all sites.

PMID- 20808457
TI  - Prevalence and antimicrobial resistance of diarrheagenic Escherichia coli and
      Shigella species associated with acute diarrhea in Tehran, Iran.
AB  - A study was performed to determine the prevalence and antimicrobial resistance of
      Shigella species and diarrheagenic Escherichia coli isolates cultured from
      patients with acute diarrhea in Tehran, Iran. Between May 2003 and May 2005, 1120
      diarrheal specimens were collected and assayed for bacterial enteropathogens by
      conventional and molecular methods. Etiological agents were isolated from 564
      (50.3%) specimens, and included 305 (54%) E coli, 157 (27.8%) Shigella species,
      and 102 (18%) from other genera of bacteria. The predominant E coli was Shiga
      toxin-producing E coli (105 isolates [34.5%]) and the predominant Shigella
      serotype was Shigella sonnei (88 isolates [56.1%]). A high rate of antibiotic
      resistance was observed among E coli, with 40 of 53 (75.5%) Shiga toxin-producing
      E coli isolates resistant to amoxicillin and tetra-cycline, and eight (5.2%) E
      coli isolates resistant to more than six antibiotics. Most Shigella isolates were
      resistant to tetracycline (95%) and trimethoprim-sulfamethoxazole (91.7%), with
      greatest antibiotic resistance observed among S sonnei (53 of 88 [60.2%]
      isolates). Antibiotic resistance is widespread in diarrheagenic E coli and
      Shigella in children with acute diarrhea in Tehran, Iran; hence, updated
      strategies for appropriate use of antimicrobial agents in Iran are needed.

PMID- 20808458
TI  - Optimal use of raltegravir (Isentress(R)) in the treatment of HIV-infected adults
      - Canadian consensus guidelines.
AB  - BACKGROUND AND OBJECTIVES: A meeting of a Canadian group with significant
      experience and knowledge in HIV management, consisting of five physicians, a
      pharmacist and an AIDS researcher, was convened. Their goal was to develop
      guidance for Canadian HIV-treating physicians on the appropriate use of
      raltegravir (MK-0518, Isentress(R), Merck Frosst Canada Inc) in HIV-infected
      adults. METHODS: Evidence from the published literature and conference
      presentations, as well as expert opinions of the group members, was considered
      and evaluated to develop the recommendations. Feedback on the draft
      recommendations was obtained from this core group, as well as from five other
      physicians and scientists across Canada with expertise in HIV treatment and
      antiretroviral drug resistance, and experience in the use of raltegravir. The
      final recommendations represent the core group's consensus agreement once all
      feedback was considered. RESULTS/CONCLUSIONS: Recommendations were developed to
      guide physicians in the optimal use of raltegravir. The issues considered
      included raltegravir's role in overall treatment strategy, efficacy, durability
      of effect, rate of viral load reduction, resistance, safety/toxicity,
      pharmacokinetics and drug interactions.

PMID- 20808460
TI  - Anaerobic brain abscess following chronic suppurative otitis media in a child
      from Uganda.
AB  - Brain abscess, while rare, confers high mortality, especially in the developing
      world. The case of a Ugandan child with a polymicrobial brain abscess including
      infection with Tissierella praeacuta/Clostridium hastiforme requiring repeated
      drainage and eventual surgical excision is reported. The case demonstrates the
      importance of considering anaerobic organisms in the treatment of children with
      brain abscess from the developing world.

PMID- 20808459
TI  - Routine immunization of adults in Canada: Review of the epidemiology of vaccine
      preventable diseases and current recommendations for primary prevention.
AB  - Vaccination is one of the greatest achievements in public health of the 20th
      century. However, the success of vaccine uptake and adherence to immunization
      guidelines seen in pediatric populations has not been observed among adult
      Canadians. As a result of the disparity in susceptibility to vaccine-preventable
      disease, there has been an increasing shift of vaccine-preventable childhood
      diseases into adult populations. Accordingly, morbidity and mortality due to
      vaccine-preventable illnesses now occur disproportionately in adults. All
      Canadians, irrespective of age, should have immunity to measles, mumps, rubella,
      tetanus, diphtheria, pertussis and varicella. All adult Canadians with
      significant medical comorbidities or those older than 65 years of age should
      receive the pneumococcal polysaccharide vaccine and yearly trivalent inactivate
      influenza vaccines. The present review summarizes the burden of illness of these
      vaccine-preventable diseases in the Canadian adult population and reviews the
      current immunization recommendations. Vaccination of all Canadians to these
      common agents remains a vital tool to decrease individual morbidity and mortality
      and reduce the overall burden of preventable disease in Canada.

PMID- 20808461
TI  - Successful treatment of a prosthetic joint infection due to Mycobacterium
      abscessus.
AB  - Prosthetic joint infection due to Mycobacterium abscessus is uncommon and optimal
      therapy remains poorly defined. Following a two-stage revision, clinical and
      microbiological cure was achieved in a patient with a M abscessus-infected total
      hip arthroplasty. A prolonged course of directed antibacterial therapy comprising
      clarithromycin and cefoxitin coupled with the application of amikacin-impregnated
      cement likely contributed to the successful outcome.

PMID- 20808462
TI  - Cryptococcemia resulting in an incomplete abortion in an HIV-positive patient.
AB  - Exotic infections and unusual presentations are the norm in immunocompromised
      patients. An unusual case of cryptococcemia resulting in a miscarriage is
      reported. This was the first presentation of the disease and the sentinel
      infection in the patient who was found to be HIV positive. Histological
      evaluation of the dilation and curettage specimen showed numerous typical
      organisms of cryptococcus present within the products of conception. There was a
      focal granulomatous response to the organisms. An accompanying cryptococcal
      endometritis was not noted. Other concomitant infections were not seen.

PMID- 20808463
TI  - Research preparedness paves the way to respond to pandemic H1N1 2009 influenza
      virus.
AB  - The international community has been preparing for an influenza pandemic because
      of the threat posed by H5N1 avian influenza. Over the past several years, Canada
      has dedicated funding to boost capacity for research, and public health and
      health care system readiness and response in the event of a pandemic. The current
      H1N1/09 influenza pandemic is now testing our readiness. From a research
      perspective, the present commentary discusses how have we prepared, along with
      the research gaps. We conclude that: sources of pandemics are not always
      predictable; investment in the past few years has paid off in a rapid response to
      pandemic H1N1/09 virus in Canada; and research to meet the challenges of
      infectious diseases has to be done on an ongoing long-term basis, and its funding
      has to be flexible, available and predictable to maintain capacity and expertise.
      In addition, new vaccine technologies are needed to develop and produce vaccines
      for public health emergencies in a timely fashion.

PMID- 20808464
TI  - Rubella immunity among pregnant women in a Canadian provincial screening program.
AB  - BACKGROUND: There are limited recent data on rubella immunity in women of
      childbearing age in Canada. In the present paper, the proportion of rubella
      seroreactivity and redundant testing (testing of women previously seropositive
      when tested by the same physician) in the Alberta prenatal rubella screening
      program were studied. METHODS: In the present retrospective observational study,
      data on all specimens submitted for prenatal screening in Alberta between August
      2002 and December 2005 were extracted from the Provincial Laboratory for Public
      Health database. The proportion of rubella screening and immunoglobulin G (IgG)
      seroreactivity were determined. Demographic variables were compared between
      rubella seroreactors and nonseroreactors. The proportion of redundant testing was
      determined. RESULTS: Of 159,046 prenatal specimens, 88.3% (n=140,473) were
      screened for rubella immunity. In total, 8.8% of specimens tested negative for
      rubella IgG. Younger women (23.2% of women younger than 20 years of age versus
      4.7% of women between 35 and 39 years of age; P<0.001) and women from northern
      Alberta (11.9% versus 8.1% [overall]; P<0.001) were significantly more likely to
      have seronegative specimens. Of the 20,044 women who had multiple rubella
      immunity screenings, 88.1% (n=17,651) had multiple positive test results. In
      total, 20.7% of the 42,274 specimens submitted from women with multiple
      screenings were deemed redundant. DISCUSSION: Younger women were most likely to
      be seronegative for rubella. The public health significance of women entering
      their childbearing years with low or undetectable rubella IgG levels remains to
      be determined. A large number of women with documented rubella immunity were
      unnecessarily retested.

PMID- 20808466
TI  - Paediatric infectious disease notes.

PMID- 20808465
TI  - Epidemiology of enteric disease in C-EnterNet's pilot site - Waterloo region,
      Ontario, 1990 to 2004.
AB  - OBJECTIVE: The objective of the present study was to describe the epidemiology of
      reportable enteric illness in Ontario's Waterloo region, including comparing
      calculated incidence rates with published rates, and adjusting for under
      reporting to determine the number of community cases, where published data were
      available. METHODS: Descriptive analyses were performed on reportable disease
      data for 13 enteric diseases collected in the Waterloo region from 1990 to 2004.
      Poisson and negative binomial regression analyses were used to investigate
      differences in incidence rates among age, sex, the 15 years of data and seasons.
      Disease-specific incidence rates were calculated and compared with the
      literature, where possible. Under-reporting ratios from the literature were
      applied to estimate the number of cases of campylobacteriosis, nontyphoidal
      salmonellosis and verotoxigenic Escherichia coli infection at the community
      level. RESULTS: Over the study period, the average annual age- and sex-adjusted
      incidence rates per 100,000 population were highest for campylobacteriosis (49.69
      cases), followed by giardiasis (31.87 cases) and nontyphoidal salmonellosis
      (25.97 cases). The incidence of most enteric illnesses peaked in the summer. The
      highest incidence occurred in young children, followed by adults in their 20s.
      Diarrhea (85.4%) was the most frequently reported symptom, food (57.4%) was the
      most commonly reported probable source, and home (41.7%) and travel (37.0%) were
      the two most frequently reported risk settings. CONCLUSIONS: Enteric illness was
      a significant health burden in the Waterloo region from 1990 to 2004. Because
      reportable disease data are subject to under-reporting, it is likely that the
      true burden is greater than estimated in the present study.

PMID- 20808467
TI  - Influenza mixes its pitches: Lessons learned to date from the influenza A (H1N1)
      pandemic.

PMID- 20808468
TI  - The dr lindsay e nicolle award.

PMID- 20808469
TI  - Developmental regression: Always a worrying signal.

PMID- 20808470
TI  - Educational services for hospitalized children.

PMID- 20808471
TI  - Sport participation, sport injury, risk factors and sport safety practices in
      Calgary and area junior high schools.
AB  - OBJECTIVES: To examine rates of sport participation, sport injury, risk factors
      and sport safety practices in young adolescents. DESIGN: Cross-sectional.
      SETTING: Calgary and area junior high schools. PARTICIPANTS: A random sample of
      1466 students (aged 12 to 15 years). OUTCOME MEASURES: Sport injury within one
      year prior to completing the survey. RESULTS: Ninety-three per cent of students
      participated in sports in the previous year. The injury rate was 60.85
      injuries/100 students/year (95% CI 58.29 to 63.35) for students reporting at
      least one sport injury, 29.4 injuries/100 students/year (95% CI 27.08 to 31.81)
      for medically treated injuries, and 12.28 injuries/100 students/year (95% CI
      10.64 to 14.07) for injuries presenting to a hospital emergency department. The
      greatest proportion of injuries occurred in basketball (14%), soccer (12%),
      hockey (8.6%) and snowboarding/skiing (7.1%). CONCLUSIONS: The rates of
      participation and injury in sports are high in junior high school students.
      Future research should focus on prevention strategies in sports with high
      participation and injury rates to have the greatest population health impact.

PMID- 20808472
TI  - The impact of jaundice in newborn infants on the length of breastfeeding.
AB  - OBJECTIVES: To examine the breastfeeding prevalence among infants aged three and
      six months who were previously hospitalized because of hyperbilirubinemia, and to
      determine whether jaundice in newborn infants increases the risk of breastfeeding
      discontinuation. METHOD: Surveys were mailed to mothers of all eligible infants
      admitted over a two-and-a-half year period to the paediatric ward of a tertiary
      care children's hospital with a diagnosis of hyperbilirubinemia. A total of 127
      mother-patient pairs were included in the study. Breastfeeding rates at three and
      six months were compared with those of a city-wide survey (Infant Care Survey)
      conducted by Ottawa's Public Health Department. Risk factors for early
      breastfeeding discontinuation were examined. RESULTS: Breastfeeding rates at
      three and six months were not different between the study group and those
      reported in the Infant Care Survey (75.5% in the study group versus 71.2% in the
      Infant Care Survey group, at three months; and 59.1% in the study group versus
      50.8% of the Infant Care Survey group, at six months). None of the previously
      reported risk factors for early weaning had an impact on breastfeeding duration
      in the study population. CONCLUSION: Breastfeeding rates following the discharge
      of infants diagnosed with jaundice were not significantly different from those
      reported for the general population. Different patient characteristics may have
      inflated the breastfeeding rates in the study population, as evidenced by a very
      high education level among the mothers of enrolled patients. Larger prospective
      studies in diverse populations are needed to determine the rates of early
      breastfeeding discontinuation in jaundiced infants.

PMID- 20808473
TI  - A case report of prenatal exposure to rosuvastatin and telmisartan.
AB  - Statins are considered to be a standard treatment for hyperlipidemia. Central
      nervous system, limb and midline defects have been reported in newborns exposed
      to statins in utero, although causality has been questioned. A 22-month-old boy
      with severe microcephaly, growth retardation, dysmorphic features, profound
      global developmental delay and peri-Sylvian polymicrogyria on brain imaging is
      presented. He was born to a mother exposed to telmisartan during the first seven
      months and rosuvastatin throughout the entire pregnancy. There were no features
      of fetopathy associated with sartans including telmisartan, such as a history of
      oligohydraminios and renal abnormalities. Given the increasing prevalence of
      obesity and its related complications (including dyslipidemias and hypertension)
      in young women of childbearing age, more safety data for prenatal exposure to
      statins and sartans are urgently needed.

PMID- 20808474
TI  - Case 1: Diagnosing difficult deglutition.

PMID- 20808475
TI  - Case 2: Hypoglycemia and micropenis in the newborn - hormonal red flags.

PMID- 20808477
TI  - Ear infections.

PMID- 20808478
TI  - What can evidence implementation learn from Barack Obama's campaign?

PMID- 20808476
TI  - Management of acute otitis media.

PMID- 20808479
TI  - Validating self-report measures of pain and function in patients undergoing hip
      or knee arthroplasty.
AB  - PURPOSE: To investigate the factorial and construct validity of a four-item pain
      intensity scale, the P4, in patients awaiting primary total hip or knee
      arthroplasty secondary to osteoarthritis. METHOD: A construct validation design
      was applied to a sample of convenience of 117 patients (mean age 65.6 [SD = 11.2]
      years) at their preoperative visit. All patients completed the P4 and the Western
      Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Exploratory and
      confirmatory factor analyses were used to examine the factorial structure of the
      P4 and WOMAC. To evaluate construct validity, we examined the correlation between
      the P4 and WOMAC pain sub-scales and the ability of the P4 to differentiate
      between patients awaiting hip and knee replacement. RESULTS: Two distinct factors
      consistent with the themes of pain and function were identified with P4 and WOMAC
      physical function items, but not with the WOMAC pain and physical function items.
      The P4 correlates more with the WOMAC pain scores (r = 0.67) than with the WOMAC
      physical function scores (r = 0.60). CONCLUSION: The P4's validity was supported
      in this patient group. The use of the P4 with the WOMAC physical function sub
      scale provides a more distinct assessment of pain and function than the WOMAC
      pain and physical function scales.

PMID- 20808481
TI  - Regional muscle and whole-body composition factors related to mobility in older
      individuals: a review.
AB  - PURPOSE: To describe previously reported locomotor muscle and whole-body
      composition factors related to mobility in older individuals. METHODS: A
      narrative review of the literature, including a combination of search terms
      related to muscle and whole-body composition factors and to mobility in older
      individuals, was carried out. Statistical measures of association and risk were
      consolidated to summarize the common effects between studies. RESULTS: Fifty
      three studies were reviewed. Muscle and whole-body factors accounted for a
      substantial amount of the variability in walking speed, with coefficients of
      determination ranging from 0.30 to 0.47. Muscle power consistently accounted for
      a greater percentage of the variance in mobility than did strength. Risks
      associated with high fat mass presented a minimum odds ratio (OR) of 0.70 and a
      maximum OR of 4.07, while the minimum and maximum ORs associated with low lean
      mass were 0.87 and 2.30 respectively. Whole-body and regional fat deposits
      accounted for significant amounts of the variance in mobility. CONCLUSION: Muscle
      power accounts for a greater amount of the variance in the level of mobility in
      older individuals than does muscle strength. Whole-body fat accounts for a
      greater amount of the variance in level of mobility than does whole-body lean
      tissue. Fat stored within muscle also appears to increase the risk of a mobility
      limitation in older individuals.

PMID- 20808482
TI  - Exploring the feasibility and efficacy of a telehealth stroke self-management
      programme: a pilot study.
AB  - PURPOSE: Moving On after STroke (MOST) is an established self-management
      programme for persons with stroke and their care partners. Through 18 sessions
      over 9 weeks, each including discussion and exercise, participants learn about
      goal-setting, problem-solving, exercise, and community-reintegration skills. This
      study was undertaken to evaluate the feasibility and efficacy of telehealth
      delivery of MOST. METHOD: Efficacy was evaluated using an experimental non
      randomized trial comparing a telehealth MOST intervention group (T-MOST) (n = 10)
      with a waiting list control group (WLC) (n = 8). Outcome measures included the
      Berg Balance Scale (BBS), the Reintegration to Normal Living Index, the Stroke
      Adapted Sickness Impact Profile, Goal Attainment Scaling, and the Geriatric
      Depression Scale. The feasibility evaluation included attendance rates, focus
      groups, and facilitator logs. In MOST Telehealth, one co-facilitator was local
      and the other was connected by videoconference. RESULTS: Attendance rates for
      persons with stroke (83.9%, SD = 2.6) and care partners (76.7%, SD = 2.9) and
      participant and facilitator experiences indicated feasibility of this mode of
      programme delivery. There was a significant difference in BBS scores between the
      T-MOST group and the WLC group (mean difference -4.27, 95%CI: -6.66 to -1.87).
      Participants reported additional benefits, including increased motivation and
      awareness of partners' needs. Videoconferencing was reported to decrease their
      sense of isolation. CONCLUSION: It appears feasible to deliver the MOST programme
      with two facilitators, one connected by videoconference and one in person. In
      addition, preliminary evidence suggests that the programme is associated with
      improved well-being in persons with stroke and their care partners. Practitioners
      delivering self-management programmes may consider wider dissemination using
      videoconferencing.

PMID- 20808483
TI  - Strategic responses to fiscal constraints: a health policy analysis of hospital
      based ambulatory physical therapy services in the Greater Toronto Area (GTA).
AB  - PURPOSE: Ambulatory physical therapy (PT) services in Canada are required to be
      insured under the Canada Health Act, but only if delivered within hospitals. The
      present study analyzed strategic responses used by hospitals in the Greater
      Toronto Area (GTA) to deliver PT services in an environment of fiscal constraint.
      METHODS: Key informant interviews (n = 47) were conducted with participants from
      all hospitals located within the GTA. RESULTS: Two primary strategic responses
      were identified: (1) "load shedding" through the elimination or reduction of
      services, and (2) "privatization" through contracting out or creating internal
      for-profit subsidiary clinics. All hospitals reported reductions in service
      delivery between 1996 and 2003, and 15.0% (7/47 hospitals) fully eliminated
      ambulatory services. Although only one of 47 hospitals contracted out services,
      another 15.0% (7/47) reported that for-profit subsidiary clinics were created
      within the hospital in order to access other more profitable forms of quasi
      public and private funding. CONCLUSIONS: Strategic restructuring of services,
      aimed primarily at cost containment, may have yielded short-term financial
      savings but has also created a ripple effect across the continuum of care.
      Moreover, the rise of for-profit subsidiary clinics operating within not-for
      profit hospitals has emerged without much public debate and with little research
      to evaluate its impact.

PMID- 20808485
TI  - Postgraduate physiotherapy training: interest and perceived barriers to
      participation in a clinical master's degree programme.
AB  - PURPOSE: To (1) assess whether physiotherapists in a large Canadian province
      support the offering of a clinical master's degree programme; (2) identify what
      sector of this population is interested in participating in a clinical master's
      degree programme; (3) identify the most common personal/professional reasons for
      enrolling; (4) identify the type of programme that would appeal; and (5) assess
      barriers to participation in such a programme. METHODS: The survey and
      accompanying cover letter explaining the study were sent by postal mail to all
      2,552 physiotherapists registered with the College of Physical Therapists of
      British Columbia (CPTBC). RESULTS: The response rate was 17%; 90% of respondents
      support offering this type of physiotherapy degree in BC, and 14% reported that
      they were likely to enrol. Orthopaedics/manual therapy (41%) was the clinical
      area of most interest. CONCLUSIONS: There is strong support for a clinical
      master's degree in orthopaedic manual therapy in BC. There is greater support for
      a part-time programme with an inter-professional component, using a combination
      of e-learning and classroom teaching to reduce travel time and time away from
      family.

PMID- 20808486
TI  - Effect of acute exercise on upper-limb volume in breast cancer survivors: a pilot
      study.
AB  - PURPOSE: Strenuous upper-extremity activity and/or exercise have traditionally
      been prescribed for breast cancer survivors with or at risk of developing
      lymphedema. The purpose of this study was to assess the effect of an acute bout
      of exercise on upper-limb volume and symptoms in breast cancer survivors, with
      the intent to provide pilot data to guide a subsequent larger study. METHODS:
      Twenty-three women who regularly participated in dragon-boat racing took part in
      the study. A single exercise bout was performed at a moderate intensity (rating
      of perceived exertion: 13-14) for 20 continuous minutes on an arm ergometer. The
      difference between affected and unaffected limb volume was assessed pre- and post
      exercise via measurements of limb circumference at five time points. RESULTS:
      Although limb volume increased following exercise in both limbs, the difference
      between the limbs remained stable at each measurement point. Only one participant
      was found to have an increase in arm-volume difference of >100 ml post
      intervention, and only four participants reported symptoms of tension and/or
      heaviness in the affected limb. CONCLUSION: The results suggest that limb volume
      in breast cancer survivors increases after an acute bout of upper-limb exercise
      but that, for the majority of women, the response is not different between
      affected and unaffected limbs. Future research using a larger sample and more
      sensitive measurement methods are recommended.

PMID- 20808487
TI  - "I think it, but don't often write it": the barriers to charting in private
      practice.
AB  - PURPOSE: To describe barriers to charting identified by physiotherapists working
      in private practice in New Brunswick. METHOD: Physiotherapists were invited to
      focus-group interviews to discuss the results of a comprehensive chart audit.
      Sixty-nine physiotherapists who responded were assigned to nine focus groups.
      Seven of nine audiotaped interviews (49 participants) were of sufficient quality
      to be transcribed and imported into qualitative data analysis software for
      thematic analysis. RESULTS: Participants described the challenges of including
      charting in their routine client care. Barriers included the disjuncture between
      charting and thinking, the translation of impairment goals to functional goals,
      the time it takes to chart, fear of failure, and the difficulty of predicting
      length of treatment. Strategies to facilitate charting were suggested by
      participants. CONCLUSION: Understanding barriers to charting in private practice
      is necessary to improve the quality of documentation. Barriers described are
      related to the fast-moving nonverbal, kinaesthetic, and cognitive process that is
      clinical reasoning in physiotherapy. This tacit, implicit process is mismatched
      with the charting task, which requires that the implicit become explicit in
      written form. Strategies to facilitate charting noted by participants address
      some of these issues; however, a broader, profession-wide discussion is
      necessary.

PMID- 20808490
TI  - Objective vs. subjective: the challenge of clear documentation of range of
      motion.

PMID- 20808492
TI  - Acquisition of intraverbal behavior: teaching children with autism to mand for
      answers to questions.
AB  - Four boys with autism were taught via echoic prompting and constant prompt delay
      to mand for answers to questions by saying "I don't know please tell me"
      (IDKPTM). This intervention resulted in acquisition of the IDKPTM response for
      all 4 participants and in acquisition of correct answers to most of the
      previously unknown questions for 2 participants. For 1 participant, tangible
      reinforcement resulted in increased frequency of correct answers, and direct
      prompting of correct answers was eventually conducted for the final participant.
      The IDKPTM response generalized to untargeted unknown questions with 3
      participants. Results of person and setting generalization probes varied, but
      some generalization eventually occurred for all participants following additional
      training or interspersal of probe trials with training trials.

PMID- 20808493
TI  - Teaching brain-behavior relations economically with stimulus equivalence
      technology.
AB  - Instructional interventions based on stimulus equivalence provide learners with
      the opportunity to acquire skills that are not directly taught, thereby improving
      the efficiency of instructional efforts. The present report describes a study in
      which equivalence-based instruction was used to teach college students facts
      regarding brain anatomy and function. The instruction involved creating two
      classes of stimuli that students understood as being related. Because the two
      classes shared a common member, they spontaneously merged, thereby increasing the
      yield of emergent relations. Overall, students mastered more than twice as many
      facts as were explicitly taught, thus demonstrating the potential of equivalence
      based instruction to reduce the amount of student investment that is required to
      master advanced academic topics.

PMID- 20808494
TI  - Consistent visual analyses of intrasubject data.
AB  - Visual inspection of single-case data is the primary method of interpretation of
      the effects of an independent variable on a dependent variable in applied
      behavior analysis. The purpose of the current study was to replicate and extend
      the results of DeProspero and Cohen (1979) by reexamining the consistency of
      visual analysis across raters. We recruited members of the board of editors and
      associate editors for the Journal of Applied Behavior Analysis to judge graphs on
      a 100-point scale of experimental control and by providing a dichotomous response
      (i.e., "yes" or "no" for experimental control). Results showed high interrater
      agreement across the three types of graphs, suggesting that visual inspection can
      lead to consistent interpretation of single-case data among well-trained raters.

PMID- 20808495
TI  - Effects of treatment integrity failures during differential reinforcement of
      alternative behavior: a translational model.
AB  - Differential reinforcement of alternative behavior (DRA) is used frequently as a
      treatment for problem behavior. Previous studies on treatment integrity failures
      during DRA suggest that the intervention is robust, but research has not yet
      investigated the effects of different types of integrity failures. We examined
      the effects of two types of integrity failures on DRA, starting with a human
      operant procedure and extending the results to children with disabilities in a
      school setting. Human operant results (Experiment 1) showed that conditions
      involving reinforcement for problem behavior were more detrimental than failing
      to reinforce appropriate behavior alone, and that condition order affected the
      results. Experiments 2 and 3 replicated the effects of combined errors and
      sequence effects during actual treatment implementation.

PMID- 20808496
TI  - Descriptive analyses of pediatric food refusal and acceptance.
AB  - Functional analyses of inappropriate mealtime behavior typically include
      conditions to determine if the contingent delivery of attention, tangible items,
      or escape reinforce food refusal. In the current investigation, descriptive
      analyses were conducted for 25 children who had been admitted to a program for
      the assessment and treatment of food refusal to determine if the consequences
      commonly delivered during functional analyses were observed during parent
      conducted meals. The conditional probabilities for the delivery of attention,
      tangible items, and escape following food refusal and acceptance were compared to
      the unconditional probabilities of each event. Results showed that attention and
      escape most frequently followed refusal and differed depending on the topography
      of refusal. Implications for further evaluations of food refusal using similar
      methods are discussed.

PMID- 20808497
TI  - Use of sounding out to improve spelling in young children.
AB  - We examined the effects of teaching 5 typically developing elementary students to
      sound out their spelling words while writing them using the cover-copy-compare
      (CCC) method to practice spelling. Each student's posttest performance following
      practice with sounding out was compared to that student's posttest performance
      following practice with no sounding out. For every student, posttest accuracy was
      higher following practice with sounding out, indicating that it is an effective
      and easily implemented strategy to improve spelling instruction.

PMID- 20808498
TI  - On the relation between reinforcer efficacy and preference.
AB  - Most research on stimulus preference and reinforcer assessment involves a
      preference assessment that is followed by a reinforcer assessment. Typically, the
      most and least preferred stimuli are tested as reinforcers. In the current study,
      we first quantified the reinforcing efficacies of six food items and then
      assessed relative preference for each item. Relative preference ranking and
      reinforcer efficacies showed almost perfect concordance for 1 participant and
      partial concordance for the other. Discordance tended to occur with the weakest
      reinforcers.

PMID- 20808499
TI  - Increasing the variety of foods consumed by a picky eater: generalization of
      effects across caregivers and settings.
AB  - A multiple baseline across settings was used to evaluate the effects of
      differential reinforcement of alternative behavior, nonremoval of the fork (Hoch,
      Babbitt, Coe, Krell, & Hackbert, 1994), and stimulus fading on consumption of
      food rejected previously. The study was conducted in two separate settings, and
      caregivers were trained in the intervention technique to increase generalization
      to natural settings. Food variety increased in both settings.

PMID- 20808500
TI  - Teaching abduction-prevention skills to children with autism.
AB  - Three children with autism were taught abduction-prevention skills using
      behavioral skills training with in situ feedback. All children acquired the
      skills, which were maintained at a 1-month follow-up assessment. In addition, 1
      of the children demonstrated the skills during a stimulus generalization probe in
      a community setting.

PMID- 20808501
TI  - Functional analysis and treatment of elopement across two school settings.
AB  - The elopement of a child with Asperger syndrome was assessed using functional
      analyses and was treated in two school settings (classroom and resource room).
      Functional analyses indicated that elopement was maintained by access to
      attention in the resource room and obtaining a preferred activity in the
      classroom. Attention- and tangible-based interventions were compared in an
      alternating treatments design in both settings. Results validated the findings of
      the functional analyses. Implications for the assessment and treatment of
      elopement are discussed.

PMID- 20808502
TI  - Abolishing and establishing operation analyses of social attention as positive
      reinforcement for problem behavior.
AB  - Three participants whose problem behavior was maintained by contingent attention
      were exposed to 45-min presessions in which attention was withheld, provided on a
      fixed-time (FT) 15-s schedule, or provided on an FT 120-s schedule. Following
      each presession, participants were then tested in a 15-min session similar to the
      social attention condition of an analogue functional analysis. The results showed
      establishing operation conditions increased problem behavior during tests and
      that abolishing operation conditions decreased problem behavior during tests.

PMID- 20808503
TI  - Manipulating slot machine preference in problem gamblers through contextual
      control.
AB  - Pathological and nonpathological gamblers completed a task that assessed
      preference among 2 concurrently available slot machines. Subsequent assessments
      of choice were conducted after various attempts to transfer contextual functions
      associated with irrelevant characteristics of the slot machines. Results
      indicated that the nonproblem gambling group, but not the problem gambling group,
      increased their responding toward the slot initially trained as greater than
      following the initial training procedure, then decreased their responding toward
      that slot following the reversal phase.

PMID- 20808504
TI  - Using complex auditory-visual samples to produce emergent relations in children
      with autism.
AB  - Six participants with autism learned conditional relations between complex
      auditory-visual sample stimuli (dictated words and pictures) and simple visual
      comparisons (printed words) using matching-to-sample training procedures. Pre-
      and posttests examined potential stimulus control by each element of the complex
      sample when presented individually and emergence of additional conditional
      relations and oral labeling. Tests revealed class-consistent performance for all
      participants following training.

PMID- 20808505
TI  - Problem behavior during preference assessments: an empirical analysis and
      practical recommendations.
AB  - Preferences of 2 children with developmental disabilities, whose functional
      analyses indicated that their problem behavior was maintained by access to
      tangible items, were assessed using three formats (i.e., paired stimulus [PS],
      multiple-stimulus without replacement [MSWO], and free operant [FO]). The
      experimenter administered each format five times and compared levels of problem
      behavior across formats in a multielement design. Both participants exhibited
      problem behavior in PS and MSWO formats but not in the FO format. Results are
      discussed in terms of recommendations for practitioners.

PMID- 20808506
TI  - Assessment of the relative effects of attention and escape on noncompliance.
AB  - The current study presents a method for assessing the relative effects of
      attention and escape on noncompliance in preschoolers. Attention and escape
      conditions were alternated in a multielement design, and a contingency reversal
      procedure, in which one test condition served as a control for the other, was
      used to demonstrate control. For all 3 participants, noncompliance was
      maintained, at least in part, by social attention. Functional analyses of
      noncompliance such as the one described here may be valuable for developing
      function-based treatments.

PMID- 20808507
TI  - The effects of fixed-time escape on inappropriate and appropriate classroom
      behavior.
AB  - Few studies have explored the effects of fixed-time (FT) reinforcement on escape
      maintained behavior of students in a classroom setting. We measured the effects
      of an FT schedule on the disruptive and appropriate academic behaviors of 2
      junior high students in a public school setting. Results demonstrated that FT
      escape from tasks resulted in a substantial decrease in disruptive behavior and
      an increase in time engaged in tasks for both participants.

PMID- 20808509
TI  - In memoriam: Sidney W. Bijou.

PMID- 20808510
TI  - Skin endocrinology and nutrition.

PMID- 20808508
TI  - Recent studies on feeding problems in children with autism.
AB  - This paper reviews recent studies on behavioral interventions for children with
      autism and feeding problems. The applicability of interventions that have been
      tested with other populations of children with feeding problems is discussed, as
      well as directions for future research.

PMID- 20808511
TI  - The skin as an endocrine organ.
AB  - Through the definition of novel biological activities of hormones and their
      diversity on different skin cell types, it has become apparent that the skin
      itself possesses the capacity to generate several hormones and substances with
      hormone-like activity. These substances appear to act through paracrine,
      autocrine, intracrine and endocrine mechanisms to fulfill their pleiotropic
      effects. Also new is the knowledge that the skin can metabolize hormones and
      produce derivatives with potentially systemic activity. These findings point
      towards novel concepts in our understanding of the role of skin and of its
      hormones as important players in homeostasis and disorders of the entire human
      organism. Finally, the scientists active in the field of dermato-endocrinology
      expect that their activities will exploit the pharmacological and therapeutic
      function of hormone mediators, their receptors and antagonists. The latter idea
      has already been realized for corticosteroids, androgens, estrogens, topical
      vitamin D analogues and retinoids which have today an established place in
      clinical dermatology.

PMID- 20808514
TI  - Skin signs in anorexia nervosa.
AB  - Anorexia nervosa (AN) is a significant cause of morbidity and mortality among
      adolescent females and young women. AN is associated with severe medical and
      psychological consequences, including death, osteoporosis, growth delay, and
      developmental delay. Skin signs are almost always detectable in severe AN and
      awareness of them may help in the early diagnosis of hidden AN. Skin signs are
      the expression of the medical consequences of starvation, vomiting, abuse of
      drugs, such as laxatives and diuretics, and of the psychiatric morbidity. They
      include xerosis, lanugo-like body hair, telogen effluvium, carotenoderma, acne,
      hyperpigmentation, seborrhoeic dermatitis, acrocyanosis, perniosis, petechiae,
      livedo reticularis, interdigital intertrigo, paronychia, acquired striae
      distensae, acral coldness.The most characteristic cutaneous sign of vomiting is
      Russell's sign (knuckle calluses). Symptoms due to laxative or diuretic abuse
      include adverse reactions by drugs. Symptoms due to psychiatric morbidity
      (artefacta) include the consequences of self-induced trauma. The role of the
      dermatologist in the management of eating disorders is to make an early diagnosis
      of the "hidden" signs of eating disorders in patients who tend to minimize or
      deny their disorder.

PMID- 20808513
TI  - The relationship of diet and acne: A review.

PMID- 20808512
TI  - Cutaneous vitamin D synthesis versus skin cancer development: The Janus faces of
      solar UV-radiation.
AB  - In scientific and public communities, there is an ongoing discussion how to
      balance between positive and negative effects of solar UV-exposure. On the one
      hand, solar UV-radiation represents the most important environmental risk factor
      for the development of non-melanoma skin cancer. Consequently, UV protection is
      an important measure to prevent these malignancies, especially in risk groups.
      Otherwise, approximately 90% of all vitamin D needed by the human body has to be
      formed in the skin through the action of UV-radiation. This dilemma represents a
      serious problem, for an association of vitamin D-deficiency and multiple
      independent diseases including various types of cancer, bone diseases, autoimmune
      diseases, infectious diseases, cardiovascular diseases and hypertension has now
      been reported in a large number of investigative and epidemiologic studies. As a
      consequence, it has been assumed that for the general population in the US,
      Europe and other countries, the net effects of solar UV B-radiation on human
      health are beneficial at or near current levels. We and others have shown that
      strict sun protection causes vitamin D-deficiency/insufficiency and that
      detection and treatment of vitamin D-deficiency in sun deprived risk groups is of
      high importance. Although further work is necessary to define an adequate vitamin
      D-status and adequate guidelines for solar and artificial UV-exposure, it is at
      present mandatory that public health campaigns and sun protection recommendations
      to prevent skin cancer consider these facts. In this review, we analyze the
      present literature to help developing well-balanced recommendations on sun
      protection that ensure an adequate vitamin D-status. These recommendations will
      hopefully protect us against adverse effects of UV protection without
      significantly increasing the risk to develop UV-induced skin cancer.

PMID- 20808515
TI  - Nutrition and nutritional supplementation: Impact on skin health and beauty.
AB  - Skin acts as a natural barrier between internal and external environments thus
      plays an important role in vital biological functions such as protection against
      mechanical/chemical damages, micro-organisms, ultraviolet damage. Nutrition has a
      critical impact on strengthening skin's capabilities to fight against these
      multiple aggressions.Nutritional deficiencies are often associated with skin
      health disorders, while diets can either positively or negatively influence skin
      condition. More recently, the concept of nutritional supplementation has emerged
      as a new strategy in the daily practice of dermatology as well as a complementary
      approach to topical cosmetics in the field of beauty. Focusing on human clinical
      data, this paper proposes to illustrate the link between skin health and
      nutrition and to exemplify the beneficial actions of nutritional supplementation
      in skin health and beauty.

PMID- 20808517
TI  - Plant genomics in the 21 century.

PMID- 20808516
TI  - Probiotics for photoprotection.
AB  - Specific strains of probiotic, have been identified as beneficial to influence
      the composition and/or metabolic activity of the endogenous microbiota and some
      of these strains have been also shown to inhibit the growth of a wide range of
      enteropathogens. The first aim of using probiotics has been to improve the
      composition of the intestinal microbiota from a potentially harmful composition
      towards a composition that would be beneficial to the host.Beyond their capacity
      to influence positively the composition of the intestinal microbiota, several
      lines of evidence suggest that some probiotic bacteria can modulate the immune
      system both at the local and systemic levels thereby improving immune defense
      mechanisms and/or downregulate immune disorders such as allergies or intestinal
      inflammation.Skin reflects the general health status and aging. Different human
      trials widely suggest that probiotic supplementation might be useful in the
      management of atopic dermatitis. Based on these properties it appears that,
      beyond the gut, probiotics might exert their benefits at the skin level.In a
      randomized double blind placebo-controlled clinical trial, we investigated
      whether the probiotic bacteria Lactobacillus johnsonii NCC 533 (La1) could
      modulate the cutaneous immune homeostasis altered by solar-simulated UV exposure
      in humans. After, UV exposure to twice 1.5 MED, we demonstrated that La1 intake
      facilitated an earlier recovery of Epidermal cells allostimulatory function.
      Thus, this clinical data strengthen the assumption that certain probiotics can
      contribute to modulate skin immune system leading to the preservation of the skin
      homeostasis. Altogether the data affords the possibility of designing new
      strategies based on a nutritional approach for the prevention of UV-induced
      damaging effects.

PMID- 20808518
TI  - Expressional analysis and role of calcium regulated kinases in abiotic stress
      signaling.
AB  - Perception of stimuli and activation of a signaling cascade is an intrinsic
      characteristic feature of all living organisms. Till date, several signaling
      pathways have been elucidated that are involved in multiple facets of growth and
      development of an organism. Exposure to unfavorable stimuli or stress condition
      activates different signaling cascades in both plants and animal. Being sessile,
      plants cannot move away from an unfavorable condition, and hence activate the
      molecular machinery to cope up or adjust against that particular stress
      condition. In plants, role of calcium as second messenger has been studied in
      detail in both abiotic and biotic stress signaling. Several calcium sensor
      proteins such as calmodulin (CaM), calcium dependent protein kinases (CDPK) and
      calcinuerin B-like (CBL) were discovered to play a crucial role in abiotic stress
      signaling in plants. Unlike CDPK, CBL and CaM are calcium-binding proteins, which
      do not have any protein kinase enzyme activity and interact with a target protein
      kinase termed as CBL-interacting protein kinase (CIPK) and CaM kinases
      respectively. Genome sequence analysis of Arabidopsis and rice has led to the
      identification of multigene familes of these calcium signaling protein kinases.
      Individual and global gene expression analysis of these protein kinase family
      members has been analyzed under several developmental and different abiotic
      stress conditions. In this review, we are trying to overview and emphasize the
      expressional analysis of calcium signaling protein kinases under different
      abiotic stress and developmental stages, and linking the expression to possible
      function for these kinases.

PMID- 20808519
TI  - Small RNA diversity in plants and its impact in development.
AB  - MicroRNAs are a class of non-coding RNAs involved in post-transcriptional control
      of gene expression, either via degradation or translational inhibition of target
      mRNAs. Both experimental and computational approaches have been used to identify
      miRNAs and their target genes. In plants, deep sequencing methods have recently
      allowed the analysis of small RNA diversity in different species and/or mutants.
      Most sequencing efforts have been concentrated on the identification of miRNAs
      and their mRNA targets have been predicted based on complementarity criteria. The
      recent demonstration that certain plant miRNAs could act partly via inhibition of
      protein translation certainly opens new fields of analysis for plant miRNA
      function on a broader group of targets. The roles of conserved miRNAs on target
      mRNA stability have been analysed in different species and defined common
      mechanisms in development and stress responses. In contrast, much less is known
      about expression patterns or functions of non-conserved miRNAs. In this review,
      we focus on the comparative analyses of plant small RNA diversity and the action
      of si/miRNAs in post-transcriptional regulation of some key genes involved in
      root development.

PMID- 20808520
TI  - Application of functional genomics and proteomics to plant cryopreservation.
AB  - Plant cryobiology has primarily emerged from the classical fields of cryobiology
      and plant stress physiology. Cryopreservation tools are now available to
      geneticists for germplasm preservation and the field itself is advancing
      significantly through the use of molecular techniques. Long-term preservation of
      vegetatively propagated tissues can minimize the risks of long-term maintenance
      under tissue culture or field conditions. Cells can be successfully cryopreserved
      when the adverse affects of ice crystal formation are mitigated by the removal of
      water or procedures to limit ice formation and crystal growth. The addition of
      cryoprotectant solutions to hydrated cells may improve the survival of
      microdissected shoot tips or embryonic axes. Recent discoveries in the genetic
      pathways leading to cold acclimation and freezing tolerance suggest the
      involvement of key cold-regulated genes in the acquisition of cold tolerance in
      plant tissues. Model systems of banana and Arabidopsis have revealed the
      involvement of genes and proteins in the glycolytic and other metabolic pathways,
      particularly processes involved in dehydration tolerance, osmoprotection, and
      membrane transport. Furthermore, successful recovery appears to be dependent upon
      the presence of antioxidant protection from reactive oxygen species.
      Characterization of specific genes and proteins will lead to significant advances
      in plant cryobiology research.

PMID- 20808521
TI  - Genomics of fungal disease resistance in tomato.
AB  - Tomato (Solanum lycopersicum) is an important vegetable crop worldwide. Often
      times, its production is hindered by fungal diseases. Important fungal diseases
      limiting tomato production are late blight, caused by Phytophthora infestans,
      early blight, caused by Alternaria solanii, and septoria leaf spot, caused by
      Septoria lycopersici, fusarium wilt caused by Fusarium oxysporium fsp.
      oxysporium, and verticilium wilt caused by Verticilium dahlea. The Phytophthora
      infestans is the same fungus that caused the devastating loss of potato in Europe
      in 1845. A similar magnitude of crop loss in tomato has not occurred but
      Phytophthora infestans has caused the complete loss of tomato crops around the
      world on a small scale. Several attempts have been made through conventional
      breeding and the molecular biological approaches to understand the biology of
      host-pathogen interaction so that the disease can be managed and crop loss
      prevented. In this review, we present a comprehensive analysis of information
      produced by molecular genetic and genomic experiments on host-pathogen
      interactions of late blight, early blight, septoria leaf spot, verticilim wilt
      and fusarium wilt in tomato. Furthermore, approaches adopted to manage these
      diseases in tomato including genetic transformation are presented. Attempts made
      to link molecular markers with putative genes and their use in crop improvement
      are discussed.

PMID- 20808523
TI  - Genomics for weed science.
AB  - Numerous genomic-based studies have provided insight to the physiological and
      evolutionary processes involved in developmental and environmental processes of
      model plants such as arabidopsis and rice. However, far fewer efforts have been
      attempted to use genomic resources to study physiological and evolutionary
      processes of weedy plants. Genomics-based tools such as extensive EST databases
      and microarrays have been developed for a limited number of weedy species,
      although application of information and resources developed for model plants and
      crops are possible and have been exploited. These tools have just begun to
      provide insights into the response of these weeds to herbivore and pathogen
      attack, survival of extreme environmental conditions, and interaction with crops.
      The potential of these tools to illuminate mechanisms controlling the traits that
      allow weeds to invade novel habitats, survive extreme environments, and that make
      weeds difficult to eradicate have potential for both improving crops and
      developing novel methods to control weeds.

PMID- 20808522
TI  - Plant protein-protein interaction network and interactome.
AB  - Protein-protein interaction network represents an important aspect of systems
      biology. The understanding of the plant protein-protein interaction network and
      interactome will provide crucial insights into the regulation of plant
      developmental, physiological, and pathological processes. In this review, we will
      first define the concept of plant interactome and the protein-protein interaction
      network. The significance of the plant interactome study will be discussed. We
      will then compare the pros and cons for different strategies for interactome
      mapping including yeast two-hybrid system (Y2H), affinity purification mass
      spectrometry (AP-MS), bimolecular fluorescence complementation (BiFC), and in
      silico prediction. The application of these platforms on specific plant biology
      questions will be further discussed. The recent advancements revealed the great
      potential for plant protein-protein interaction network and interactome to
      elucidate molecular mechanisms for signal transduction, stress responses, cell
      cycle control, pattern formation, and others. Mapping the plant interactome in
      model species will provide important guideline for the future study of plant
      biology.

PMID- 20808524
TI  - Ascorbic Acid and gene expression: another example of regulation of gene
      expression by small molecules?
AB  - Ascorbic acid (vitamin C, AA) has long been considered a food supplement
      necessary for life and for preventing scurvy. However, it has been reported that
      other small molecules such as retinoic acid (vitamin A) and different forms of
      calciferol (vitamin D) are directly involved in regulating the expression of
      numerous genes. These molecules bind to receptors that are differentially
      expressed in the embryo and are therefore crucial signalling molecules in
      vertebrate development. The question is: is ascorbic acid also a signalling
      molecule that regulates gene expression?We therefore present and discuss recent
      publications that demonstrate that AA regulates the expression of a battery of
      genes. We offer a clue to understanding the biochemical mechanism by which AA
      regulates gene expression. Finally we will discuss the question of a receptor for
      AA and its potential involvement in embryonic development and cell
      differentiation.

PMID- 20808525
TI  - Simulation of genes and genomes forward in time.
AB  - The importance of simulation software in current and future evolutionary and
      genomic studies is just confirmed by the recent publication of several new
      simulation tools. The forward-in-time simulation strategy has, therefore, re
      emerged as a complement of coalescent simulation. Additionally, more efficient
      coalescent algorithms, the same as new ideas about the combined use of backward
      and forward strategies have recently appeared. In the present work, a previous
      review is updated to include some new forward simulation tools. When simulating
      at the genome-scale the conflict between efficiency (i.e. execution speed and
      memory usage) and flexibility (i.e. complex modeling capabilities) emerges. This
      is the pivot around which simulation of evolutionary processes should improve. In
      addition, some effort should be made to consider the process of developing
      simulation tools from the point of view of the software engineering theory.
      Finally, some new ideas and technologies as general purpose graphic processing
      units are commented.

PMID- 20808528
TI  - Surgery for malignant maxillary tumors involving the middle cranial fossa.
AB  - The purpose of this study was to evaluate the disease-free survival (DFS) of
      patients with maxillary malignant tumors invading the middle cranial fossa (MCF)
      who underwent a lateral or anterolateral skull base resection. This study was a
      retrospective analysis in a tertiary referral center and included 62 patients
      with maxillary malignant tumors invading the MCF (stage T4b) treated with surgery
      with or without postoperative radiotherapy. All patients had sharp pain and
      involvement of at least one branch of the trigeminal nerve. Twenty-eight patients
      had not been treated previously, and 34 had previously been treated elsewhere.
      The MCF dura was infiltrated and resected in 36 cases, and in nine of these,
      there was an intradural extension of the tumor, with temporal lobe and/or
      cavernous sinus invasion. Thirty-six patients underwent reconstruction with a
      temporalis muscle pedicled flap, and 26 patients with a free flap. There was a
      22% overall rate of postoperative complications, but no intraoperative deaths.
      The median follow-up time was 49 months (range 2 to 186). Overall DFS was 33.9%
      and was higher for untreated patients (46.4% versus 23.5%) and for patients in
      whom clean margins were achieved (51.4% versus 12.5%). The survival time for
      patients who died of disease was 9 months for squamous cell carcinoma and 38
      months for adenoid-cystic carcinoma. All patients experienced anesthesia in the
      territory of the resected trigeminal branches, but their pain vanished, and their
      quality of life improved. Lateral skull base surgery may achieve satisfactory
      oncologic results for patients with low-grade tumors, with improved quality of
      life for almost all patients.

PMID- 20808526
TI  - Revolver and superior: novel transposon-like gene families of the plant kingdom.
AB  - High-throughput sequencing of eukaryotic genomes has revived interest in the
      structure and function of repetitive genomic sequences, previously referred to as
      junk DNA. Repetitive sequences, including transposable elements, are now believed
      to play a significant role in genomic differentiation and evolution. Some are
      also expressed as regulatory noncoding RNAs. Vast DNA databases exist for higher
      eukaryotes; however, with the exception of homologues of known repetitive
      sequence-families and transposable elements, most repetitive elements still need
      to be annotated. Revolver and Superior, both discovered in the Triticeae, are
      novel classes of transposon-like genes and major components of large cereal
      genomes. Revolver was isolated from rye via genome subtraction of sequences
      common to rye and wheat. Superior was isolated from rye by cleavage with
      EcoO109I, the recognition sites of which consist of a 5'- PuGGNCCPy-3' multi
      sequence. Revolver is 2929-3041 bp long with an inverted repeat sequence on each
      end. The Superior family elements are 1292-1432 bp in length, with divergent 5'
      regions, indicating the presence of considerable structural diversity. Revolver
      and Superior are transcriptionally active elements; Revolver harbors a single
      gene consisting of three exons and two introns, encoding a protein of 139 amino
      acid residues. Revolver variants range in size from 2665 bp to 4269 bp, with some
      variants lacking the 5' region, indicating structural diversity around the first
      exon. Revolver and Superior are dispersed across all seven chromosomes of rye.
      Revolver has existed since the diploid progenitor of wheat, and has been
      amplified or lost in several species during the evolution of the Triticeae. This
      article reviews the recently discovered Revolver and Superior families of plant
      transposons, which do not share identity with any known autonomous transposable
      elements or repetitive elements from any living species.

PMID- 20808527
TI  - Investigation of molecular mechanism of chronic pain in the anterior cingulate
      cortex using genetically engineered mice.
AB  - Recent advances into the understanding of molecular mechanism of chronic pain
      have been largely developed through the use of genetic manipulations. This is in
      part due to the scarcity of selective pharmacological tools, which can be readily
      solved by creating knockout or transgenic mice. By identifying new genes that are
      of import, our efforts can then be aimed at studying relevant signaling pathways,
      and combination of pharmacological manipulations with genetic models can be used
      to further examine the specific mechanisms involved in chronic pain. In this
      review, we will examine the genetic models that are currently in use to study
      chronic pain in the anterior cingulate cortex: knockout mice; transgenic mice;
      and the strength of combining pharmacology with these genetic models.

PMID- 20808529
TI  - Sinonasal undifferentiated carcinoma: a 13-year experience at a single
      institution.
AB  - We present our experience with sinonasal undifferentiated carcinoma at the
      University of Michigan over 13 years and review prior published data. We
      conducted a retrospective review of 19 patients who presented to a tertiary care
      academic center multidisciplinary skull base clinic with sinonasal
      undifferentiated carcinoma between 1995 and 2008. Overall survival was 22% at 5
      years, and the estimated 5-year distant metastasis-free survival was 35%. At 2
      years, local control was 83%, regional control was 50%, and distant control was
      83%. Local control was best in those patients treated nonsurgically, as was
      median survival, though this was not statistically significant. Nodal disease in
      the neck, either at presentation or at recurrence, was noted in 26% of patients.
      Survival for sinonasal undifferentiated carcinoma remains poor. It is possible
      that up-front radiation or chemoradiation will lead to better local control
      rates, though surgery remains a mainstay of treatment. In all cases, the cervical
      nodes should be addressed with primary treatment.

PMID- 20808530
TI  - Light at the end of the tunnel: the learning curve associated with endoscopic
      transsphenoidal skull base surgery.
AB  - Endoscopic transsphenoidal resection of skull base lesions has been introduced
      widely as an alternative to microscopic transmucosal approaches. We report the
      introduction of this technique to our unit, including the learning curve
      recognized for this procedure, comparing techniques in a concurrent case-control
      fashion. All patients operated on for sellar, suprasellar, or clival lesions were
      considered for endoscopic surgery, with 51 patients undergoing endoscopic surgery
      and 46 having microscopic surgery with the operating method determined by the
      availability of the ear, nose, and throat surgeon involved with the procedures.
      Endoscopic surgery compared favorably with microscopic surgery with respect to
      endocrine control, length of stay, diabetes insipidus, and cerebrospinal fluid
      leakage. A learning curve was found with a significant fall in complication rates
      between the first third and most recent third of the cohort. Endoscopic skull
      base surgery has superior results to microscopic approaches once the initial
      learning curve is overcome, but this can be done quickly and safely.

PMID- 20808531
TI  - Results of anterior skull base surgery in pediatric and young adult patients.
AB  - We sought to better define the results of anterior skull base surgery in
      pediatric and young adult patients. We performed a single-institution,
      retrospective cohort study in a tertiary-care academic cancer center. Between
      1973 and 2005, 234 patients underwent anterior skull base surgery at Memorial
      Sloan-Kettering Cancer Center. Of these, 19 patients were <21 years of age.
      Surgical indications, findings, and complications were reviewed. Survival
      outcomes were analyzed using the Kaplan-Meier method and compared with patients
      >/=21 years old. Nineteen patients <21 years old underwent a total of 20
      procedures for lesions of the anterior skull base. Sarcoma was the most common
      indication for surgery including 6 (32%) patients treated for radiation-induced
      malignancies. Minor complications were noted with 6 (30%) procedures. There were
      no major complications and no perioperative deaths. The difference in 3-year
      recurrence-free (68% versus 59%; p = 0.623) and overall survival (83% versus 66%;
      p = 0.309) compared with patients >/=21 years old did not reach statistical
      significance. Anterior skull base surgery is well tolerated in pediatric and
      young adult patients <21 years of age. Survival is comparable to older patients
      treated similarly and appears strongly influenced by histology.

PMID- 20808532
TI  - Transcondylar fossa (supracondylar transjugular tubercle) approach: anatomic
      basis for the approach, surgical procedures, and surgical experience.
AB  - The authors clarify the anatomic basis and the usefulness of the transcondylar
      fossa approach (T-C-F A), in which the posterior portion of the jugular tubercle
      is removed extradurally through the condylar fossa with the atlanto-occipital
      joint intact. The authors first performed an anatomic study to identify the area
      to be removed using cadaveric specimens and then applied the T-C-F A to foramen
      magnum surgeries. The surgeries included clipping a vertebral artery-posterior
      inferior cerebellar artery aneurysm in 11 cases, microvascular decompression for
      glossopharyngeal neuralgia in 15 cases, and removing intradural foramen magnum
      tumors in 17 cases. Only the condylar fossa was removed, but the approach offered
      very good visualization of the lateral part of the foramen magnum and sufficient
      working space. These surgeries were performed safely without major complications.
      This skull base approach is minimally invasive and is not difficult. Therefore,
      it can be a standard approach for accessing intradural lesions of the foramen
      magnum. It can be combined with the transcerebellomedullary fissure approach from
      the lateral side and can also be easily changed to the transcondylar approach, if
      necessary.

PMID- 20808533
TI  - Temporal craniotomy for surgical access to the infratemporal fossa.
AB  - We propose a surgical approach for select patients that minimizes morbidity while
      allowing gross total resection of lesions in the anterior portion of the
      infratemporal fossa. The approach we describe is an extradural approach through a
      subtemporal craniectomy or craniotomy with the possible addition of a zygomatic
      osteotomy. Lesions that have a well-defined capsule and a texture that permits
      manipulation are ideal for this less invasive approach. We retrospectively
      reviewed six cases from the primary author (C.B.H.) using a temporal craniectomy
      or craniotomy alone to resect lesions in the infratemporal fossa. All six cases
      had good clinical outcomes with no unexpected neurological deficits while
      achieving gross total resections. The only complication included one
      cerebrospinal fluid leak that was sealed endoscopically. For select lesions, a
      less morbid surgical approach via an extradural window through a subtemporal
      craniectomy or small craniotomy may be preferable to transfacial approaches.
      Adjuvant use of endoscopic techniques may facilitate surgical exposure and
      resection of large lesions.

PMID- 20808534
TI  - Chondromyxoid fibroma of the skull base invading the occipitocervical junction:
      report of a unique case and discussion.
AB  - Chondromyxoid fibroma (CMF) is a rare bone tumor representing less than 1% of
      total bone neoplasms. It is a slow-growing, locally destructive tumor that
      usually affects the metaphyseal region of long bones. The occurrence of this
      tumor in the skull base or cervical spine is exceptionally rare. We present the
      first case of CMF originating in the clivus and extending into the atlas and
      discuss the surgical management of this case.

PMID- 20808535
TI  - Vagoglossopharyngeal-associated syncope due to a retained bullet in the jugular
      foramen.
AB  - Gunshot wounds (GSWs) to the head are frequently fatal. Rarely, the bullet may
      lodge in the skull base and not cause significant brain injury. Typically, the
      bullet fragments are felt to be inert and do not require operative extirpation if
      they are within the bony confines of the skull base. We report the case of a
      bullet in the jugular foramen causing recurrent syncope that resolved after
      surgical removal of the bullet. The medical records from a patient who suffered a
      GSW to the head were retrospectively reviewed and the treatment and outcome
      documented. In 2000, a 20-year-old man suffered a GSW to the head. Immediate
      evaluation revealed the bullet in the right skull base at the jugular foramen,
      but no parenchymal brain injury. One year after the GSW, he began to experience
      stereotypical spells resulting in loss of consciousness. Extensive cardiovascular
      workup was normal. In 2002, the patient underwent removal of the bullet. He has
      been syncope-free since the operation and returned to his career in the military.
      We believe the retained bullet in this patient was irritating the IX-X cranial
      nerves, resulting in syncope, similar to the mechanism in vagoglossopharyngeal
      neuralgia. Removing the bullet relieved the irritation and stopped the syncopal
      spells.

PMID- 20808536
TI  - Clivus chordoma: is it enough to image the primary site?
AB  - Chordomas are rare malignant tumors arising from embryonic remnants of the
      primitive notochord, around which the skull base and vertebral column develop.
      They are locally aggressive but metastasize rarely. To our knowledge, this is the
      first reported case of synchronous intraosseous chordomas. A 32-year-old man
      presented with intermittent double vision secondary to a right-side abducent
      nerve palsy. Imaging revealed a clivus chordoma and an asymptomatic synchronous
      second primary chordoma in the fifth lumbar vertebra. Both chordomas were
      surgically excised: the clivus using the endonasal, endoscopic route and the L5
      vertebra by total vertebral excision and replacement with a titanium prosthesis.
      The patient made an uneventful and complete recovery. We have modified our
      departmental practice as we believe that all patients diagnosed with chordoma
      should have magnetic resonance imaging of their entire spinal tract to exclude a
      second primary chordoma.

PMID- 20808537
TI  - Intracochlear schwannoma.
AB  - Intralabyrinthine schwannomas are benign, slow-growing tumors that originate from
      Schwann cells lining the terminal ends of the cochlear and vestibular nerves.
      Magnetic resonance imaging (MRI) with gadolinium is considered the best
      diagnostic tool for this disease. Kennedy et al proposed a classification system,
      based upon the MRI observations, that identifies seven different classes
      according to the site of the tumor: intravestibular, intracochlear,
      intravestibulocochlear, transmodiolar, transmacular, transotic, and
      tympanolabyrinthine. A case of a patient undergoing a 2-year follow-up with
      serial MRI and managed with a wait-and-see strategy is described. The rationale
      of the diagnosis and the different treatments of choice are discussed.

PMID- 20808538
TI  - Median facial cleft with a frontoethmoidal encephalocele treated with
      craniofacial bipartition and free radial forearm flap: a case report.
AB  - We describe a patient with a median facial cleft with a frontoethmoidal
      encephalocele, hypertelorism, hydrocephalus, and cerebrospinal fluid (CSF)
      leakage referred to our department due to numerous complications after previous
      surgical treatments. An 8-year-old girl, born with median cleft syndrome,
      underwent neurosurgical repair of the encephalocele at another hospital and cleft
      lip/palate repair later in the same year. Her hydrocephalus was treated with a
      ventriculoperitoneal shunt, but she underwent numerous shunt revisions due to
      recurrent intracerebral infections. In 2008, she was rehospitalized due to a gram
      negative meningitis and cerebral abscess. She underwent surgery where part of her
      frontal bone was removed due to osteomyelitis. She was referred to our department
      due to persistent CSF leakage, recurrent infections, and significant dura defect.
      In addition, she had hypertelorism and a strongly reduced vision. We performed a
      monobloc and facial bipartition osteotomy where 15 mm of her frontal and nasal
      bone was removed after facial bipartiton. The dura defect was closed using a free
      fasciocutanous flap. The patient had no CSF leakage or infections
      postoperatively, and her hypertelorism was reduced. The case represents the first
      monobloc and facial bipartition osteotomy performed in Norway as a part of the
      treatment of median cleft syndrome with a nasoethmoidal encephalocele.

PMID- 20808540
TI  - Molecular pharmacology of the GABA(A) receptor.

PMID- 20808539
TI  - Chordoid glioma: ten years of a low-grade tumor with high morbidity.
AB  - We report two new cases of chordoid glioma of the third ventricle and review all
      previously published cases of this rare tumor with regard to presentation,
      optimum management, and outcome. Two new cases are reported with the radiological
      and histopathologic findings. We searched and cross-referenced PubMed and
      published reports of this tumor to retrieve an additional 51 cases of this tumor,
      which were then analyzed according to a proforma. Chordoid glioma has consistent
      radiological features, although some atypical elements including a cystic
      component are well described. The insidious presentation and morbidity of
      attempted surgical resection combine to give high overall morbidity. There is a
      high incidence of postoperative thromboembolic disturbance. Adjuvant radiosurgery
      has a promising role. The morbidity of this condition is likely to remain high
      but may be minimized by a less aggressive surgical approach together with
      surveillance and early use of radiosurgery.

PMID- 20808541
TI  - General anesthetic actions on GABA(A) receptors.
AB  - General anesthetic drugs interact with many receptors in the nervous system, but
      only a handful of these interactions are critical for producing anesthesia. Over
      the last 20 years, neuropharmacologists have revealed that one of the most
      important target sites for general anesthetics is the GABA(A) receptor. In this
      review we will discuss what is known about anesthetic - GABA(A) receptor
      interactions.

PMID- 20808542
TI  - Context dependent benzodiazepine modulation of GABA(A) receptor opening
      frequency.
AB  - The anxiolytic, hypnotic, and anti-convulsant properties of benzodiazepines
      (BDZs) require modulation of distinct GABA(A) receptor alpha-subtypes. BDZ
      modulation of GABA(A) receptors is often described in terms of increased opening
      frequency, and contrasted with the increased open durations occurring with
      barbiturate modulation. Several studies spanning single channel, rapid kinetic,
      and whole cell techniques have suggested that BDZs effect this observed change in
      frequency through increased affinity for GABA. BDZ-sensitive alphabetagamma
      isoforms exist at extrasynaptic as well as synaptic locations, where they
      encounter markedly different concentration and time-course of GABA exposure.
      Interestingly, this affinity-based mechanism (specifically, decreasing the GABA
      unbinding rate) is only predicted to increase opening frequency under conditions
      that allow the unbinding and rebinding cycles typical of prolonged exposure to
      low GABA concentrations, which are more likely to occur at extrasynaptic GABA(A)
      receptors. In contrast, when rebinding is less likely, such as may occur in
      certain synaptic conditions, the number, but not the frequency, of channel
      openings increases in response to BDZ modulation. In conclusion, not only can
      multiple kinetic mechanisms alter channel opening frequency, but a single
      mechanism - increased affinity - impacts opening frequency differently under
      different contexts of GABA(A) receptor activation.

PMID- 20808543
TI  - Kinetic and structural determinants for GABA-A receptor potentiation by
      neuroactive steroids.
AB  - Endogenous neurosteroids and synthetic neuroactive steroid analogs are among the
      most potent and efficacious potentiators of the mammalian GABA-A receptor. The
      compounds interact with one or more sites on the receptor leading to an increase
      in the channel open probability through a set of changes in the open and closed
      time distributions. The endogenous neurosteroid allopregnanolone potentiates the
      alpha1beta2gamma2L GABA-A receptor by enhancing the mean duration and prevalence
      of the longest-lived open time component and by reducing the prevalence of the
      longest-lived intracluster closed time component. Thus the channel mean open time
      is increased and the mean closed time duration is decreased, resulting in
      potentiation of channel function. Some of the other previously characterized
      neurosteroids and steroid analogs act through similar mechanisms while others
      affect a subset of these parameters. The steroids modulate the GABA-A receptor
      through interactions with the membrane-spanning region of the receptor. However,
      the number of binding sites that mediate the actions of steroids is unclear. We
      discuss data supporting the notions of a single site vs. multiple sites mediating
      the potentiating actions of steroids.

PMID- 20808544
TI  - Neuropharmacology of vestibular system disorders.
AB  - This work reviews the neuropharmacology of the vestibular system, with an
      emphasis on the mechanism of action of drugs used in the treatment of vestibular
      disorders. Otolaryngologists are confronted with a rapidly changing field in
      which advances in the knowledge of ionic channel function and synaptic
      transmission mechanisms have led to the development of new scientific models for
      the understanding of vestibular dysfunction and its management. In particular,
      there have been recent advances in our knowledge of the fundamental mechanisms of
      vestibular system function and drug mechanisms of action. In this work, drugs
      acting on vestibular system have been grouped into two main categories according
      to their primary mechanisms of action: those with effects on neurotransmitters
      and neuromodulator receptors and those that act on voltage-gated ion channels.
      Particular attention is given in this review to drugs that may provide additional
      insight into the pathophysiology of vestibular diseases. A critical review of the
      pharmacology and highlights of the major advances are discussed in each case.

PMID- 20808546
TI  - Cyclooxygenase and neuroinflammation in Parkinson's disease neurodegeneration.
AB  - Cyclooxygenase (COX) expression in the brain is associated with pro-inflammatory
      activities, which are instrumental in neurodegenerative processes such as
      Parkinson's disease (PD). It is discussed that drugs with the capacity to rescue
      dopaminergic neurons from microglia toxicity and neuroinflammatory processes may
      result in an amelioration of parkinsonian symptoms by delaying the onset or
      slowing progression. This article reviews the involvement of COX in
      neuroinflammation, specifically focussing at the role of selective COX-2
      inhibition in neuroinflammation and neurodegeneration in Parkinson's disease.

PMID- 20808550
TI  - Victimized again?

PMID- 20808545
TI  - Past, present and future therapeutics for cerebellar ataxias.
AB  - Cerebellar ataxias are a group of disabling neurological disorders. Patients
      exhibit a cerebellar syndrome and can also present with extra-cerebellar
      deficits, namely pigmentary retinopathy, extrapyramidal movement disorders,
      pyramidal signs, cortical symptoms (seizures, cognitive impairment/behavioural
      symptoms), and peripheral neuropathy. Recently, deficits in cognitive operations
      have been unraveled. Cerebellar ataxias are heterogeneous both at the phenotypic
      and genotypic point of view. Therapeutical trials performed during these last 4
      decades have failed in most cases, in particular because drugs were not targeting
      a deleterious pathway, but were given to counteract putative defects in
      neurotransmission. The identification of the causative mutations of many
      hereditary ataxias, the development of relevant animal models and the recent
      identifications of the molecular mechanisms underlying ataxias are impacting on
      the development of new drugs. We provide an overview of the pharmacological
      treatments currently used in the clinical practice and we discuss the drugs under
      development.

PMID- 20808551
TI  - Challenges to National Cancer Institute-Supported Cooperative Group Clinical
      Trial Participation: An ASCO Survey of Cooperative Group Sites.
AB  - Anecdotal information regarding clinical research sites limiting participation in
      NCI-funded cooperative group studies prompted ASCO to collect data on and
      investigate the reasons behind this trend.

PMID- 20808552
TI  - Commentary: timing is everything.

PMID- 20808547
TI  - Update on the pharmacological treatment of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder. Worldwide
      prevalence of the disease is estimated at more than 24 million cases. With aging
      of populations, this number will likely increase to more than 80 million cases by
      the year 2040. The annual incidence worldwide is estimated at 4.6 million cases
      which is the equivalent of one new case every seven seconds! The pathophysiology
      of AD is complex and largely misunderstood. It is thought to start with the
      accumulation of beta-amyloid (alphabeta) that leads to deposition of insoluble
      neuritic or senile plaques. Secondary events in this "amyloid cascade" include
      hyperphosphorylation of the protein tau into neurofibrillary tangles,
      inflammation, oxidation, and excitotoxicity that eventually cause activation of
      apoptotis, cell death and neurotransmitter deficits. This review will briefly
      summarize recent advances in the pathophysiology of AD and focus on the
      pharmacological treatment of the cognitive and functional symptoms of AD. It will
      discuss the roles of vascular prevention, cholinesterase inhibitors and an NMDA
      antagonist in the management of AD. It will address the issues thought to be
      related to the lack of persistence or discontinuation of therapy with
      cholinesterase inhibitors shown in recent studies and some of the solutions
      proposed. These include setting realistic expectations in light of a
      neurodegenerative condition and available symptomatic treatments, slowly
      titrating medications, and using alternate routes of administration. Finally, it
      will introduce future therapeutic options currently under study.

PMID- 20808553
TI  - Importance of testing for usability when selecting and implementing an electronic
      health or medical record system.
AB  - PURPOSE: An oncology electronic health record (EHR) was implemented without prior
      usability testing. Before expanding the system to new clinics, this study was
      initiated to examine the role of usability testing in the evaluation of an EHR
      product and whether novice users could identify issues with usability that
      resonated with more experienced users of the system. In addition, our study
      evaluated whether usability issues with an already implemented system affect
      efficiency and satisfaction of users. METHODS: A general usability guide was
      developed by a group of five informaticists. Using this guide, four novice users
      evaluated an EHR product and identified issues. A panel of five experts reviewed
      the identified issues to determine agreement with and applicability to the
      already implemented system. A survey of 42 experienced users of the previously
      implemented EHR was also performed to assess efficiency and general satisfaction.
      RESULTS: The novice users identified 110 usability issues. Our expert panel
      agreed with 90% of the issues and recommendations for correction identified by
      the novice users. Our survey had a 54% response rate. The majority of the
      experienced users of the previously implemented system, which did not benefit
      from upfront usability testing, had a high degree of dissatisfaction with
      efficiency and general functionality but higher overall satisfaction than
      expected. CONCLUSION: In addition to reviewing features and content of an EHR
      system, usability testing could improve the chances that the EHR design is
      integrated with existing workflow and business processes in a clear and efficient
      way.

PMID- 20808554
TI  - Commentary: electronic health records and human performance.

PMID- 20808555
TI  - Statewide cancer clinical trial navigation service.
AB  - PURPOSE: Realizing that education and awareness are paramount in making clinical
      trials available to improve overall accrual rates, we sought to create a clinical
      trial navigation service to improve the accessibility of cancer clinical trials
      in Florida for physicians and patients. This study was undertaken to evaluate
      this service. We hoped to identify characteristics of our service that were
      effective in promoting clinical trial enrollment and to better understand
      barriers that prevented enrollment. METHODS: Qualitative and quantitative data
      were gathered to inform the evaluation. This information was drawn from
      semistructured interview and focus groups as well as data from 6,350 patient
      questionnaires capturing diagnosis, stage, and treatment history. Quantitative
      data were analyzed by computing indices of central tendency and dispersion as
      well as frequency distributions. Qualitative data were analyzed using open coding
      to identify major themes representing the information. RESULTS: Our navigation
      system increased patient awareness of trials; however, this did not lead to an
      increase in trial enrollment. A key barrier to enrollment was the timing of the
      patient's awareness of a clinical trial opportunity. Often trial options were
      realized after a treatment course was initiated. This frequently disqualified the
      patient from trial consideration. We identified factors underlying the critical
      role of how physician attitudes toward trials affect enrollment. We also found
      that government databases were incomplete. Twenty-five percent of clinical trials
      open in Florida were not listed with Physician Data Query or clinicaltrials.gov,
      and 15% to 22% were erroneously listed as having sites in Florida. Media efforts
      to increase patient awareness and use of the navigation service were transient.
      One-time educational programs did not have a long-term impact on clinical trial
      inquiries. Patients who spoke with clinical trial navigators were four times more
      likely to contact a matched trial site. Sharing a common database platform with
      various organizations increased the likelihood of patients finding trials near
      home. More than 82% of patients seeking information started their search on other
      Web sites. CONCLUSION: Although we were able to overcome the barriers most
      commonly cited by patients, we found that taking a strictly patient-focused
      approach was not enough. Our results underline the critical role of health
      professionals in guiding patients to clinical trials, by including these options
      at a time when patients are likely to be eligible.

PMID- 20808556
TI  - Pegfilgrastim on the Same Day Versus Next Day of Chemotherapy in Patients With
      Breast Cancer, Non-Small-Cell Lung Cancer, Ovarian Cancer, and Non-Hodgkin's
      Lymphoma: Results of Four Multicenter, Double-Blind, Randomized Phase II Studies.
AB  - PURPOSE: To compare data on severe (grade 4) neutropenia duration and febrile
      neutropenia incidence in patients receiving chemotherapy with pegfilgrastim
      administered the same day or 24 hours after chemotherapy. PATIENTS AND METHODS:
      These were similar, randomized, double-blind phase II noninferiority studies of
      patients with lymphoma or non-small-cell lung (NSCLC), breast, or ovarian cancer.
      Each study was analyzed separately. The primary end point in each study was cycle
      1 severe neutropenia duration. Approximately 90 patients per study were to be
      randomly assigned at a ratio of 1:1 to receive pegfilgrastim 6 mg once per cycle
      on the day of chemotherapy or the day after (with placebo on the alternate day).
      RESULTS: In four studies, 272 patients received chemotherapy and one or more
      doses of pegfilgrastim (133 same day, 139 next day). Three studies (breast,
      lymphoma, NSCLC) enrolled an adequate number of patients for analysis. However,
      in the NSCLC study, the neutropenic rate was lower than expected (only two
      patients per arm experienced grade 4 neutropenia). In the breast cancer study,
      the mean cycle-1 severe neutropenia duration was 1.2 days (95% confidence limit
      [CL], 0.7 to 1.6) longer in the same-day compared with the next-day group (mean,
      2.6 v 1.4 days). In the lymphoma study, the mean cycle-1 severe neutropenia
      duration was 0.9 days (95% CL, 0.3 to 1.4) longer in the same-day compared with
      the next-day group (mean, 2.1 v 1.2 days). In the breast and lymphoma studies,
      the absolute neutrophil count profile for same-day patients was earlier, deeper,
      and longer compared with that for next-day patients, although the results
      indicate that same-day administration was statistically noninferior to next-day
      administration according to neutropenia duration. CONCLUSION: For patients
      receiving pegfilgrastim with chemotherapy, pegfilgrastim administered 24 hours
      after chemotherapy completion is recommended.

PMID- 20808557
TI  - Description of current practices of empiric chemotherapy dose adjustment in obese
      adult patients.
AB  - PURPOSE: The literature is not clear on the best method to empirically dose
      chemotherapy in obese adult patients. The purpose of our study was to determine
      whether a standard of practice existed, characterize current practices of empiric
      dose adjustment (EDA) in obese adult patients, and identify factors affecting
      this decision. METHODS: An electronic survey was distributed to oncologists and
      board-certified oncology pharmacists via the Association of Community Cancer
      Centers and Board of Pharmaceutical Specialties e-mail distribution lists. The
      survey contained patient scenarios assessing the impact of various factors on EDA
      of chemotherapy, demographic information, and details of institutional policies.
      RESULTS: Responses were collected from 174 professionals. Pharmacists comprised
      95% of respondents. Of these, 50% practiced in academic medical centers, and 19%
      practiced in institutions with a standard of practice regarding EDA for obesity.
      The most common methods of EDA were use of an adjusted body weight in the body
      surface area (BSA) equation and capping BSA. Factors with the most impact on EDA
      were curative intent, degree of obesity, type of chemotherapy, and performance
      status. CONCLUSION: There is no standard of practice regarding EDA of
      chemotherapy in obese adult patients. Although many factors affect this decision,
      intent of treatment, degree of obesity, performance status, age, and type of
      medication seem to carry the most weight.

PMID- 20808558
TI  - Daily life as an Australian medical oncologist.
AB  - Several models of practice exist in Australia, presenting benefits and challenges
      to the physicians involved and the communities for which they care.

PMID- 20808559
TI  - How we treat febrile neutropenia in patients receiving cancer chemotherapy.
AB  - Although improved supportive care has reduced mortality associated with febrile
      neutropenia, it continues to cause chemotherapy limitations, morbidity,
      mortality, and cost among patients with cancer.

PMID- 20808560
TI  - Use of locum tenens physicians in oncology practice.
AB  - Who would step in to care for your patients if you had to be away from work for
      several weeks? Calling in a locum tenens oncologist may be a good solution.

PMID- 20808561
TI  - Cancer genomics: conducting exemplary trials with biospecimen and biomarker
      components.
AB  - Translating research on genomic changes into novel interventions for patients
      with cancer requires increased analysis of biospecimens and biomarkers in cancer
      clinical trials, which involve certain procedural requirements.

PMID- 20808562
TI  - Caveat emptor.
AB  - Until there is a clearer understanding of the role that genes of low penetrance
      play in cancer risk, the best advice may be: Buyer beware.

PMID- 20808563
TI  - Clinical trial information as a measure of quality cancer care.
AB  - Participation in clinical trials enables patients to access new treatment
      options. Evidence shows improved outcomes in participants compared with
      nonparticipants in non-small-cell, lung, breast, colorectal, and testicular
      cancers.

PMID- 20808564
TI  - New H1N1 influenza virus infection: Focus on humans and animals interface - A
      comment.

PMID- 20808565
TI  - Antibiotics and poultry - A comment.

PMID- 20808568
TI  - An outbreak of bovine tuberculosis in an intensively managed conservation herd of
      wild bison in the Northwest Territories.
AB  - An outbreak of bovine tuberculosis was detected in the Hook Lake Wood Bison
      Recovery Project captive-breeding herd in March 2005. This study investigates the
      most likely source of Mycobacterium bovis and identifies difficulties associated
      with salvaging tuberculosis-free animals from an endemically infected herd.

PMID- 20808569
TI  - Spinal cord injury II: Prognostic indicators, standards of care, and clinical
      trials.
AB  - This is the second of a 2-part review of spinal cord injury. The focus herein is
      to highlight recent findings regarding prognostic indicators used for spinal cord
      injury (SCI) in dogs, promote an awareness of the current recommendations of
      standard of care for traumatic spinal cord injury in veterinary medicine, and
      highlight the findings of clinical trials of therapies for spinal cord injury in
      dogs. This 2-part review provides information that will assist general and
      specialty veterinary practitioners in evidence-based veterinary medical practice
      in an area that has become particularly specialized.

PMID- 20808570
TI  - Avian chlamydiophilosis in a Manitoba farmed pigeon flock.

PMID- 20808571
TI  - Effect of biotin supplementation on claw horn growth in young, clinically healthy
      cattle.
AB  - The effects of orally administered biotin supplementation on the growth of claw
      horn in young, clinically healthy cattle were analyzed. Twelve, 1-year-old
      Girolando cattle were randomly assigned to receive either 12.5 mg of diluted
      powdered biotin (GI) or a control treatment (GII) for 40 consecutive days. Cattle
      in the GI group showed an average hoof growth of 11.3 +/- 0.72 mm, while those in
      GII had an average hoof growth of 7.2 +/- 0.78 mm. The results confirmed the
      positive effect of biotin supplementation on the growth of angle and length of
      the dorsal hoof wall, hoof sole length, and on resistance to wearing, in young
      cattle extensively managed.

PMID- 20808572
TI  - Bovine enucleation: A retrospective study of 53 cases (1998-2006).
AB  - Medical records of 53 cattle undergoing enucleation (1998-2006) were reviewed.
      Assessments of the outcomes were done via client surveys. Descriptive statistics
      were generated on the affected population, the underlying disease, the
      complications, and the length of retention within the herd. Hereford cattle
      comprised the majority of the cases (30/53; 57%). Most cattle (84.9%) were
      diagnosed with ocular squamous cell carcinoma (OSCC). Follow-up information was
      available for 22 cattle. Para-orbital infection was documented in 10 of 53 cattle
      (19%). Five cattle died of various causes 2 months to several years after
      enucleation. One cow was culled due to recurrence of OSCC. Fifteen cattle were
      retained within their respective herds. This study documents that orbital
      infections are common, and recurrence of OSCC is infrequent in cattle having
      undergone enucleation.

PMID- 20808573
TI  - Clinicopathological evaluation of downer dairy cows with fatty liver.
AB  - This study evaluated the relationship between severity of fatty liver and
      macromineral status in downer dairy cows and determined the usefulness of
      selected biochemical analytes for assessing prognosis. Blood and liver biopsy
      specimens were obtained from 36 Holstein downer cows shortly after the cows
      became recumbent and before they were treated. Liver tissue was examined
      histologically and serum activity of liver-derived enzymes and concentration of
      total lipids, triglycerides, bile acids, glucose, beta-hydroxybutyrate,
      acetoacetic acid, total bilirubin, non-esterified fatty acids (NEFA), cholesterol
      and macrominerals (Ca, Mg, K, Na, P) were determined. Fatty liver infiltration
      was severe in 44% of the cows and moderate in 44%. Serum activities of ornithine
      carbamoyltransferase and glutamate dehydrogenase, and NEFA/cholesterol ratio were
      good indicators of fatty liver. Cows with severe fatty liver had the lowest mean
      K values. The prognosis is guarded for downer cows with moderate and severe fatty
      liver and when total bilirubin concentration is high.

PMID- 20808574
TI  - Prognostic indicators of poor outcome in horses with laminitis at a tertiary care
      hospital.
AB  - This retrospective study investigated the factors associated with a poor outcome
      (death by euthanasia or from other causes) in horses treated for laminitis at a
      tertiary care hospital. Cases (n = 247) were defined as patients with laminitis
      that were euthanized or that died of other causes during hospitalization.
      Controls (n = 344) were patients with laminitis that survived to be discharged
      from the hospital. In the final multivariate analysis, the factors significantly
      associated with an increased risk for death and their respective odds ratios (OR)
      were as follows: Thoroughbred (OR = 1.57); racehorse (OR = 1.76); treatment with
      flunixin meglumine (OR = 1.76); vascular pathology (OR = 2.12); distal
      displacement of the third phalanx (OR = 2.68); pneumonia (OR = 2.87); and
      lameness of Obel grade II (OR = 2.99), grade III (OR = 9.63), or grade IV (OR =
      20.48). The use of glue-on shoes significantly reduced the risk for death (OR =
      0.36).

PMID- 20808575
TI  - Comparison of polymerase chain reaction tests for diagnosis of feline
      herpesvirus, Chlamydophila felis, and Mycoplasma spp. infection in cats with
      ocular disease in Canada.
AB  - This study assessed the value of polymerase chain reaction (PCR) for making a
      diagnosis of feline herpesvirus (FHV-1) infection, and for differentiating this
      from Chlamydophila felis and Mycoplasma spp. infection in a clinical setting in
      Canada. We compared the frequency of positive FHV-1 PCR test results from 48
      clinical cases of ocular disease in cats suspected to be due to FHV-1 between 1
      research and 2 commercial laboratories in Canada. We also compared PCR results
      for Chlamydophila felis and Mycoplasma spp. between the 2 commercial
      laboratories. The prevalence of FHV-1 infection in the cats ranged from 4% to
      21%. The prevalence of Chlamydophila felis was 2% and 17% and the prevalence of
      Mycoplasma spp. was 11% and 27%. Agreement between FHV-1 culture and PCR results
      at the research laboratory was substantial (kappa = 0.76). There was slight
      agreement (kappa < 0.20) between the 3 laboratories for FHV-1 PCR and between the
      2 commercial laboratories for both Chlamydophila felis (kappa = 0.2) and
      Mycoplasma spp. (kappa = 0.07) PCR.

PMID- 20808576
TI  - The prevalence of bacterial contamination of surgical cold sterile solutions from
      community companion animal veterinary practices in southern Ontario.
AB  - Surgical cold sterile solutions are commonly used in veterinary practice, yet
      sterility cannot be verified under practical clinical conditions. Surgical cold
      sterile solutions were sampled and bacteria, including opportunistic pathogens,
      were recovered from 13% of the sampled solutions. Attempts to sterilize surgical
      instruments with cold sterile solutions should be avoided.

PMID- 20808577
TI  - Hand-assisted laparoscopic removal of a nephroblastoma in a horse.
AB  - A 3-year-old Thoroughbred was presented for evaluation of hematuria post
      exercise. On physical examination, an enlarged kidney was identified, as well as
      serum biochemical abnormalities such as an elevated creatine kinase (CK) and
      hypoalbuminemia. The kidney was removed laparoscopically and a nephroblastoma was
      identified.

PMID- 20808578
TI  - Prevalence and diagnosis of Giardia infection in dogs and cats using a fecal
      antigen test and fecal smear.
AB  - The SNAP fecal enzyme-linked immunosorbent assay (ELISA) Giardia test was used to
      determine the prevalence of Giardia in dogs and cats with gastrointestinal signs.
      The test was positive in 241 (13.0%) dogs and 16 (4.1%) cats. Giardia cysts were
      detected in only 61 of the 241 dogs and 4 of the 16 cats that were test positive.

PMID- 20808579
TI  - Budgeting revisited.

PMID- 20808580
TI  - The art of knowing when to quit.

PMID- 20808581
TI  - Coat color and coat color pattern-related neurologic and neuro-ophthalmic
      diseases.

PMID- 20808582
TI  - Are we prepared for geriatric orthopedics?

PMID- 20808583
TI  - Anterior cruciate ligament reconstruction in patients with generalized joint
      laxity.
AB  - Generalized joint laxity is a genetically determined component of overall joint
      flexibility. The incidence of joint laxity in the overall population is
      approximately 5% to 20%, and its prevalence is higher in females. Recently it was
      noticed that individuals with generalized joint laxity are not only prone to
      anterior cruciate ligament injuries but also have inferior results after a
      reconstruction. Therefore, an anterior cruciate ligament reconstruction in
      patients with generalized laxity should be undertaken with caution due to the
      higher expected failure rate from the complexity of problems associated with this
      condition. It is also necessary to identify the risk factors for the injury as
      well as for the post operative outcome in this population. A criterion that
      includes all the associated components is necessary for the proper screening of
      individuals for generalized joint laxity. Graft selection for an anterior
      cruciate reconstruction in patients with ligament laxity is a challenge.
      According to the senior author, a hamstring autograft is an inferior choice and a
      double bundle reconstruction with a quadriceps tendon-bone autograft yields
      better results than a single bundle bone-patella tendon-bone autograft. Future
      studies comparing the different grafts available might be needed to determine the
      preferred graft for this subset of patients. Improved results after an anterior
      cruciate ligament reconstruction can be achieved by proper planning and careful
      attention to each step beginning from the clinical examination to the
      postoperative rehabilitation.

PMID- 20808584
TI  - Survival and prognostic analysis of adjacent segments after spinal fusion.
AB  - BACKGROUND: To examine the survival function and prognostic factors of the
      adjacent segments based on a second operation after thoracolumbar spinal fusion.
      METHODS: This retrospective study reviewed 3,188 patients (3,193 cases) who
      underwent a thoracolumbar spinal fusion at the author's hospital. Survival
      analysis was performed on the event of a second operation due to adjacent segment
      degeneration. The prognostic factors, such as the cause of the disease, surgical
      procedure, age, gender and number of fusion segments, were examined. Sagittal
      alignment and the location of the adjacent segment were measured in the second
      operation cases, and their association with the types of degeneration was
      investigated. RESULTS: One hundred seven patients, 112 cases (3.5%), underwent a
      second operation due to adjacent segment degeneration. The survival function was
      97% and 94% at 5 and 10 years after surgery, respectively, showing a 0.6% linear
      reduction per year. The significant prognostic factors were old age, degenerative
      disease, multiple-level fusion and male. Among the second operation cases, the
      locations of the adjacent segments were the thoracolumbar junctional area and
      lumbosacral area in 11.6% and 88.4% of cases, respectively. Sagittal alignment
      was negative or neutral, positive and strongly positive in 47.3%, 38.9%, and
      15.7%, respectively. Regarding the type of degeneration, spondylolisthesis or
      kyphosis, retrolisthesis, and neutral balance in the sagittal view was noted in
      13.4%, 36.6%, and 50% of cases, respectively. There was a significant difference
      according to the location of the adjacent segment (p = 0.000) and sagittal
      alignment (p = 0.041). CONCLUSIONS: The survival function of the adjacent
      segments was 94% at 10 years, which had decreased linearly by 0.6% per a year.
      The likelihood of a second operation was high in those with old age, degenerative
      disease, multiple-level fusion and male. There was a tendency for the type of
      degeneration to be spondylolisthesis or kyphosis in cases of the thoracolumbar
      junctional area and strongly positive sagittal alignment, but retrolisthesis in
      cases of the lumbosacral area and neutral or positive sagittal alignment.

PMID- 20808585
TI  - Cotyloplasty in cementless total hip arthroplasty for an insufficient acetabulum.
AB  - BACKGROUND: Cotyloplasty is a technique that involves making a perforation of the
      medial wall of a shallow acetabulum and then inserting an acetabular cup with the
      medial aspect of its dome beyond the Kohler line. The purpose of this study was
      to evaluate the results of cementless total hip arthroplasty (THA) using
      cotyloplasty with focusing on the amount of medial cup protrusion. METHODS:
      Sixteen hips with insufficient acetabulum in sixteen patients were treated by
      cementless THA using cotyloplasty. The average patient age was 47 years. The
      diagnoses included dysplastic hip (12) and infection sequelae (4). All the
      patients were followed up for at least 2 years. Clinically, the Harris hip scores
      were assessed and radiologically, the amount of cup protrusion, the hip center
      movement and cup fixation were evaluated. RESULTS: The average Harris hip score
      improved from 57 to 94 postoperatively. The average proportion of cup surface
      beyond the Kohler line was 44.1% and the hip centers were medialized by an
      average of 23 mm. Stable fixation of the acetabular cup was achieved in all the
      cases except one. In this one case, migration of the cup was detected 2 weeks
      postoperatively and a reoperation was performed. CONCLUSIONS: Using cotyloplasty,
      good coverage of the acetabular cup was obtained without a block bone graft, and
      the hip joint centers were medialized. However, the safety margin for the amount
      of protrusion should be established.

PMID- 20808586
TI  - Operative treatment of clavicle midshaft fractures: comparison between
      reconstruction plate and reconstruction locking compression plate.
AB  - BACKGROUND: To compare the outcomes of reconstruction plate and reconstruction
      locking compression plate (LCP) for the treatment of clavicle midshaft fractures.
      METHODS: Forty one patients with a clavicle midshaft fracture were treated by
      internal fixation with a reconstruction plate (19 patients) or reconstruction LCP
      (22 patients). The clinical and radiological results were evaluated according to
      the Quick Disability of the Arm, Shoulder, and Hand (DASH) score and plain
      radiographs. RESULTS: The mean time to union was 14.6 weeks in the reconstruction
      plate group compared to 13.2 weeks in the reconstruction LCP group (p > 0.05).
      The mean score to Quick DASH was 33.85 points in the reconstruction plate group
      compared to 34.81 points in the reconstruction LCP group (p > 0.05). The
      complications in the reconstruction plate were hypertrophic scarring in 2 cases,
      painful shoulder in 2 cases, limitation of shoulder motion in 2 cases, and screw
      loosening in 3 cases. In addition, the complications in the reconstruction LCP
      group was hypertrophic scarring in 4 cases, painful shoulder in 1 case and a
      limitation of shoulder motion in 1 case (p > 0.05). CONCLUSIONS: This study
      showed radiologically and clinically satisfactory results in both groups.
      Overall, operative treatment with a Reconstruction plate or reconstruction LCP
      for clavicle shaft fractures can be used to obtain stable fixation.

PMID- 20808587
TI  - Outcome after surgical treatment of pelvic sarcomas.
AB  - BACKGROUND: We present here the oncological and functional outcomes of limb
      salvage with or without reconstruction for primary sarcomas in the pelvic bone.
      METHODS: Forty-four patients who underwent pelvic resection for primary sarcomas
      involving the pelvis were reviewed. The average follow-up period was 39 months
      (range, 0 to 146 months). Chondrosarcoma (n = 17) and osteosarcoma (n = 10) were
      the most common diagnoses. Various clinicopathologic factors were analyzed in
      relation to the oncological outcomes of overall survival and local recurrence.
      The Musculoskeletal Tumor Society functional scores and complications were
      compared according to the tumor location, pelvic continuity and the type of
      resection. RESULTS: The overall 5-year survival rate was 40%. Metastasis at the
      time of diagnosis, the surgical margin and the histologic grade were the
      independent prognostic factors for survival. The surgical margin was an
      independent prognostic factor for local recurrence. An ischiopubic location of
      the tumor, restoration of pelvic continuity and hip joint reconstruction with
      total hip replacement arthroplasty were related with higher functional scores.
      Complications occurred in 50% of the patients and the complications varied
      according to the tumor location with infection being the most common
      complication. CONCLUSIONS: Achieving an adequate surgical margin is necessary for
      improving the oncological outcome of pelvic sarcomas. Restoration of the pelvic
      continuity and the hip joint improves the functional outcome. However,
      complications are common and so careful selection of the reconstruction method is
      needed.

PMID- 20808588
TI  - Evaluation of shoulder disorders by 2-[F-18]-fluoro-2-deoxy-D-glucose positron
      emission tomography and computed tomography.
AB  - BACKGROUND: Although fluorine-18-fluorodeoxyglucose (FDG) positron emission
      tomography (PET) has a limitation for localizing anatomical structures, combining
      it with computed tomography (CT) has made it more efficient for overcoming such
      limitations. This study aims to evaluate the efficacy of PET/CT for evaluating
      diseases of the shoulder. METHODS: Retrospective examination was performed on 25
      patients who underwent FDG-PET/CT scanning. All the patients were over 60 years
      of age, and they were evaluated both clinically and radiologically for shoulder
      pain. The study period was from May, 2006 to May, 2008. One of the patients had
      metastatic lesion in a shoulder and this patient was excluded from the study, so
      the total number of subjects in the study was finally 24 patients. RESULTS:
      PET/CT showed 67% sensitivity, 73% specificity, a positive predictive value of
      60%, a negative predictive value of 79%, 27% false positivity and 33% false
      negativity concerning shoulder pain. PET/CT showed negative finding in 4 cases
      that were successfully treated by operative treatment (rotator cuff tear [RCT], 3
      cases; impingement syndrome, 1 case). Negative findings were also noted in 6
      cases in which the pain subsided after conservative treatment (RCT, 1 case;
      suspected RCT, 2 cases; impingement syndrome, 3 cases). All the patients with
      osteoarthritis and rheumatoid arthritis had positive findings on PET/CT scanning.
      CONCLUSIONS: PET/CT is a useful adjunct to the existing imaging modalities to
      assess functional and pathophysiologic processes and at a very early stage, and
      so PET/CT can help physicians make better preoperative and postoperative
      decisions on treatment.

PMID- 20808589
TI  - Prospective evaluation of the effectiveness of a home-based program of isometric
      strengthening exercises: 12-month follow-up.
AB  - BACKGROUND: The aim of this prospective randomized clinical trial was to
      investigate the efficacy of a home-based program of isometric strengthening
      exercises for the treatment of the lateral epicondylitis (LE) of the distal
      humerus. We hypothesized that 1) use of isometric strengthening exercises would
      result in clinical benefits similar to those provided by medication and pain
      relief and 2) functional improvements after exercise would be time-dependent.
      METHODS: Patients were assigned to one of two groups: 1) an immediate physical
      therapy group (group I), or 2) a delayed physical therapy group (group D). Group
      I patients (n = 16) were instructed how to do the exercises at their first clinic
      visit and immediately carried out the exercise program. Group D patients (n = 15)
      learned and did the exercises after being on medications for 4 weeks. RESULTS:
      Outcomes at the 1-month clinic visit indicated that pain (measured using a visual
      analogue scale [VAS]) had been significantly reduced in group I compared to group
      D (p < 0.01). However, significant differences between groups were not found at 3
      , 6-, and 12-month follow-up for either VAS scores or Mayo elbow performance
      scores. For modified Nirschl/Pettrone scores, a significant difference between
      groups was found only at the 1-month follow-up visit. By then, the number of
      participants who returned to all activities with no pain or occasional mild pain
      was six (37%) in Group I and two (13%) in Group D (p = 0.031). At the final
      follow-up visit, 88% of all participants performed physical activities without
      pain. CONCLUSIONS: Isometric strengthening exercises done early in the course of
      LE (within 4 weeks) provides a clinically significant improvement.

PMID- 20808590
TI  - Ankle deformity secondary to acquired fibular segmental defect in children.
AB  - BACKGROUND: The authors report the long-term effect of acquired pseudoarthrosis
      of the fibula on ankle development in children during skeletal growth, and the
      results of a long-term follow-up of Langenskiold's supramalleolar synostosis to
      correct an ankle deformity induced by an acquired fibular segmental defect in
      children. METHODS: Since 1980, 19 children with acquired pseudoarthrosis of the
      fibula were treated and followed up for an average of 11 years. Pseudoarthrosis
      was the result of a fibulectomy for tumor surgery, osteomyelitis of the fibula
      and traumatic segmental loss of the fibula in 10, 6, and 3 cases, respectively.
      Initially, a Langenskiold's operation (in 4 cases) and fusion of the lateral
      malleolus to the distal tibial epiphysis (in 1 case) were performed, whereas only
      skeletal growth was monitored in the other 14 cases. After a mean follow-up of 11
      years, the valgus deformity and external tibial torsion of the ankle joint
      associated with proximal migration of the lateral malleolus needed to be treated
      with a supramallolar osteotomy in 12 cases (63%). These ankle deformities were
      evaluated using the serial radiographs and limb length scintigraphs. RESULTS: In
      all cases, early closure of the lateral part of the distal tibial physis, upward
      migration of the lateral malleolus, unstable valgus deformity and external tibial
      torsion of the ankle joint developed during a mean follow-up of 11 years (range,
      5 to 21 years). The mean valgus deformity and external tibial torsion of the
      ankle at the final follow-up were 15.2 degrees (range, 5 degrees to 35 degrees)
      and 10 degrees (range, 5 degrees to 12 degrees), respectively. In 12 cases
      (12/19, 63%), a supramalleolar corrective osteotomy was performed but three
      children had a recurrence requiring an additional supramalleolar corrective
      osteotomy 2-4 times. CONCLUSIONS: A valgus deformity and external tibial torsion
      are inevitable after acquired pseudoarthrosis of the fibula in children. Both
      Langenskiold supramalleolar synostosis to prevent these ankle deformities and
      supramalleolar corrective osteotomy to correct them in children are effective
      initially. However, both procedures cannot maintain the permanent ankle stability
      during skeletal maturity. Therefore any type of prophylactic surgery should be
      carried out before epiphyseal closure of the distal tibia occurs, but the
      possibility of a recurrence of the ankle deformities and the need for final
      corrective surgery after skeletal maturity should be considered.

PMID- 20808591
TI  - Arthroscopic treatment of septic arthritis of acromioclavicular joint.
AB  - Septic arthritis requires an early diagnosis and proper treatment to prevent the
      destruction of articular cartilage and joint contracture. This paper presents a
      rare case of septic arthritis of the acromioclavicular joint that was treated
      with arthroscopic debridement and resection of the distal clavicle.

PMID- 20808592
TI  - Calcific myonecrosis of the antetibial area.
AB  - Calcific myonecrosis is a rare late post-traumatic condition, in which a single
      muscle is replaced by a fusiform mass with central liquefaction and peripheral
      calcification. Compartment syndrome is suggested to be the underlying cause. The
      resulting mass may expand with time due to recurrent intralesional hemorrhage
      into the chronic calcified mass. A diagnosis may be difficult due to the long
      time between the original trauma and the symptoms of calcific myonecrosis. We
      encountered a 53-year-old male patient diagnosed with calcific myonecrosis in the
      lower leg. We report the case with a review of the relevant literature.

PMID- 20808593
TI  - The need for evidence-based aesthetic dermatology practice.

PMID- 20808594
TI  - Carbon dioxide laser guidelines.
AB  - The carbon dioxide (CO(2)) laser is a versatile tool that has applications in
      ablative lasing and caters to the needs of routine dermatological practice as
      well as the aesthetic, cosmetic and rejuvenation segments. This article details
      the basics of the laser physics as applicable to the CO(2) laser and offers
      guidelines for use in many of the above indications.

PMID- 20808595
TI  - A novel option of uninterrupted closure of surgical wounds.
AB  - BACKGROUND: A cosmetically pleasing postoperative scar is an important aim of all
      aesthetic surgeries. Use of proper suture materials for delicate and gentle
      suturing of the operative injury is an important requirement for achieving
      satisfactory scars. However, closure of the edges of wounds by means of
      conventional suture materials does not always meet the requirements to achieve
      this objective. AIM: To simplify and facilitate the process of surgical wound
      closure, to improve the quality of scar, and to achieve a good cosmetic effect
      through the introduction of a new type of suture material. MATERIALS AND METHODS:
      We have introduced a new surgical suturing material-a nontraumatic, barbed thread
      connected with the suture needle-APTOS SUTURE (European patent 1075843 as of
      1999). Presented herein is a new modification of the technique of uninterrupted
      subcutaneous and intracutaneous suturing of wound edges, and the details of our
      experience with this material. RESULTS: Our experience shows that, with use of
      APTOS, wound closure is carried out easily and quickly. The wound remains stable,
      the time of healing is shortened, and the process of suture removal is
      simplified, resulting in an aesthetically pleasing scar. CONCLUSIONS: The
      technique of surgical wound suturing proposed herein is a simple, facilitated,
      and efficient option of wound-edge closure, which can successfully be used, both
      in general and in aesthetic surgery for wound closure, such as plasty of scars,
      face lift, mammoplasty, and abdominal plasty.

PMID- 20808596
TI  - Q-switched Nd:YAG Laser to Treat Nevomelanocytic Nevi.
AB  - BACKGROUND: Q-switched Nd:YAG laser, a melanin pigment-specific laser was used to
      treat melanocytic nevi in Indian patients. OBJECTIVE: To assess the clinical
      response of nevi to Q-switched Nd:YAG laser of 1064 nm wavelength. MATERIALS AND
      METHODS: Nineteen patients received an average of 2.57 treatments with Q-switched
      Nd:YAG laser of 1064 nm wavelength, repetition rate of 10 Hz, 10 nanoseconds
      pulse width, and spot size of 4 mm to 6 mm with a fluence ranging from 4 to 9.7
      joules/cm(2). The clinical end point of the laser treatment was brisk whitening.
      The response was assessed by using a global assessment score. RESULTS: The
      clinical global assessment score showed excellent response in 8/19 patients and
      good response in 6/19 patients. CONCLUSION: The Q-switched Nd:YAG laser of 1064
      nm wavelength resulted in significant improvement (lightening) of nevi.

PMID- 20808597
TI  - Nicolau syndrome: an iatrogenic cutaneous necrosis.
AB  - Nicolau syndrome is an uncommon complication of intramuscular injection leading
      to variable degrees of necrosis of skin and the underlying tissues. We report
      here two cases of this syndrome. Our first case was a 25 year-old male who
      developed intense pain and purplish discoloration of the skin in the right hip
      after intramuscular diclofenac injection. The second case was a 60 year-old male
      who developed intense pain and discoloration of skin, not only at the injection
      site, but also on the left scapular area and left elbow after receiving
      chlorpheniramine maleate injection intramuscularly. These cases highlight the
      need for awareness about this condition and the need to exercise utmost care
      during the administration of any parenteral injections by dermatologists.

PMID- 20808598
TI  - Primary cutaneous anaplastic large cell lymphoma arising from lymphomatoid
      papulosis, responding to low dose methotrexate.
AB  - CD30+ cutaneous lymphoproliferative disorders (CLPDs) present variable clinical
      and histological manifestations. We report here a case of an adult male patient
      who progressed from lymphomatoid papulosis to anaplastic large cell lymphoma. The
      patient responded satisfactorily to a low dose of methotrexate.

PMID- 20808599
TI  - Does topical tretinoin used for chemoprevention cause increased mortality?

PMID- 20808600
TI  - The efficacy of silicone gel for the treatment of hypertrophic scars and keloids.
AB  - Topical self drying silicone gel is a relatively recent treatment modality
      promoted as an alternative to topical silicone gel sheeting. Thirty patients with
      scars of different types including superficial scars, hypertrophic scars, and
      keloids were treated with silicon gel application. The results of the self-drying
      silicone gel have been satisfactory.

PMID- 20808601
TI  - Multiple cream-colored papules over the trunk and neck.

PMID- 20808602
TI  - Microneedling with dermaroller.
AB  - Microneedling with dermaroller is a new treatment modality for the treatment of
      scars, especially acne scars, stretch marks, wrinkles, and for facial
      rejuvenation. It is a simple and relatively cheap modality that also can be used
      for transdermal drug delivery.

PMID- 20808603
TI  - Probiotics: the health boosters.

PMID- 20808604
TI  - Intelligent health informatics: the promise.

PMID- 20808605
TI  - The implications of health reform for health information and electronic health
      record implementation efforts.

PMID- 20808606
TI  - Health information technology and physician career satisfaction.
AB  - PURPOSE: Health information technology (HIT) and physician career satisfaction
      are associated with higher-quality medical care. However, the link between HIT
      and physician career satisfaction, which could potentially reduce provider
      burnout and attrition, has not been fully examined. This study uses a nationally
      representative survey to assess the association between key forms of HIT and
      career satisfaction among primary care physicians (PCPs) and specialty
      physicians. METHODS: We performed a retrospective, cross-sectional analysis of
      physician career satisfaction using the Community Tracking Study Physician
      Survey, 2004-2005. Nine specific types of HIT as well as the overall adoption of
      HIT in the practice were examined using multivariate logistic regression.
      RESULTS: Physicians who used five to six (odds ratio [OR] = 1.46) or seven to
      nine (OR = 1.47) types of HIT were more likely than physicians who used zero to
      two types of HIT to be "very satisfied" with their careers. Information
      technology usages for communicating with other physicians (OR = 1.31) and e
      mailing patients (OR = 1.35) were positively associated with career satisfaction.
      PCPs who used technology to write prescriptions were less likely to report career
      satisfaction (OR = 0.67), while specialists who wrote notes using technology were
      less likely to report career satisfaction (OR = 0.75). CONCLUSIONS: Using more
      information technology was the strongest positive predictor of physicians being
      very satisfied with their careers. Toward that end, healthcare organizations
      working in conjunction with providers should consider exploring ways to integrate
      various forms of HIT into practice.

PMID- 20808607
TI  - The First Anniversary of the Health Information Technology for Economic and
      Clinical Health (HITECH) Act: the regulatory outlook for implementation.

PMID- 20808608
TI  - Distributed guidelines (DiG): a software framework for extending automated health
      decision support to the general population.
AB  - This article presents a framework and methodology to create personal health
      record (PHR) systems able to transform raw health data into meaningful
      information for the general population. By bridging the semantic gap between an
      individual and his or her health data, it is expected that better care will ensue
      through consumer empowerment. An important challenge for the realization of this
      vision is the lack of available expert knowledge in a format that is
      concomitantly easy to codify, share, and be used by the general population. To
      address this challenge, we developed a novel approach to encode expert knowledge
      into machine-interpretable, reusable components called "consumer guidelines."
      Once encoded, guidelines are easily shared, extended, and modified. These
      guidelines can exist as distributed documents on the Internet and be executed by
      our processing engine (Health-Guru) to provide an individual with personalized
      assessment against various health risks based on the evidence data stored in a
      PHR.

PMID- 20808609
TI  - Development of an instrument to measure students' perceptions of information
      technology fluency skills: establishing content validity.

PMID- 20808610
TI  - Profile.

PMID- 20808611
TI  - Profile.

PMID- 20808612
TI  - Profile.

PMID- 20808613
TI  - Chiropractic science: a contemporary neurophysiologic paradigm.

PMID- 20808614
TI  - Chiropractors and collaborative care: An overview illustrated with a case report.
AB  - Although not typical, there appears to be a growing trend of chiropractors
      working within collaborative care settings. We use a case report to highlight
      features of patient care and education related to chiropractic practice within a
      collaborative care model. This paper hopes to offer some insight into how a
      chiropractor might fit into a collaborative setting and what training might help
      them to function effectively. The case report used is an example where a
      chiropractor provided a secondary diagnosis and complementary care not previously
      considered by the allied team resulting in symptom control and return to work by
      the patient. By the nature of a chiropractor's ability to provide a primary or
      secondary musculoskeletal diagnosis, they have the capacity to offer an additive
      approach to patient care within collaborative care models. However, chiropractors
      wishing to work in these environments, such as a family health team, would
      benefit from further education.

PMID- 20808615
TI  - A randomized controlled (intervention) trial of ischemic compression therapy for
      chronic carpal tunnel syndrome.
AB  - STUDY DESIGN: Randomized clinical trial. OBJECTIVE: The aim of this study was to
      evaluate the effect of ischemic compression therapy in the treatment of chronic
      carpal tunnel syndrome. METHOD: Fifty-five patients suffering from carpal tunnel
      syndrome were randomized to two groups. Thirty-seven patients received 15
      experimental treatments which consisted of ischemic compressions at trigger
      points located in the axilla of the shoulder, the length of the biceps muscle, at
      the bicipital aponeurosis and at the pronator teres muscle in the hollow of the
      elbow. Eighteen patients received the control treatment involving ischemic
      compression on trigger points located in the deltoid muscle, supraspinatus muscle
      and infraspinatus muscle. Of the 18 patients forming the control group, 13 agreed
      to receive the experimental treatments after the 15 control treatments. Outcome
      measures included a validated 18-question questionnaire to assess the severity of
      symptoms and functional status in carpal tunnel syndrome, and a quantification of
      the patients' perceived improvement, using a scale from 0% to 100%. Outcome
      measures evaluations were completed at baseline, after 15 treatments, 30 days
      following the last treatment, and 6 months later. RESULTS: For the disability
      questionnaire, a significant reduction of symptoms was noted only in the
      experimental group. In the experimental group the outcome at baseline was 33.5
      (SD, 10.3); after 15 treatments it was 18.6 (SD, 7.0). The control group outcome
      at baseline was 36.3 (SD, 15.2); after 15 treatments it was 26.4 (SD, 9.9) and
      after the crossover (15 control treatments plus 15 experimental treatments) 20.2
      (SD, 12.2). A significant between group difference (P < 0.021) was noted in the
      patients' perceived improvement after 15 treatments: 67 (SD, 26) percent and 50
      (SD, 25) percent respectively for the experimental and control groups.
      CONCLUSION: This practice-based clinical trial suggests that myofascial therapy
      using ischemic compression the length of the biceps, at the bicipital
      aponeurosis, at the pronator teres and at the subscapularis muscles could be a
      useful approach to reduce symptoms associated with the carpal tunnel syndrome.
      Patients' perceived improvement in functional capacities persisted over a 6-month
      period.

PMID- 20808616
TI  - Femoroacetabular impingement syndrome: a narrative review for the chiropractor.
AB  - OBJECTIVE: To familiarize the chiropractic clinician with the clinical
      presentation, radiographic features, and conservative versus surgical treatment
      options for managing femoroacetabular impingement (FAI) syndrome. BACKGROUND: FAI
      syndrome is a relatively new clinical entity to be described in orthopedics, and
      has been strongly linked with pain and early osteoarthritis of the hip in young
      adults. Hip joint radiographs in these patients often appear normal at first
      particularly if the clinician is unfamiliar with FAI. The role of conservative
      therapy in managing this disorder is questionable. Surgical treatment ultimately
      addresses any acetabular labral or articular cartilage damage, as well as the
      underlying osseous abnormalities associated with FAI. The most commonly used
      approach is open surgical hip dislocation; however, more recent surgical
      procedures also involve arthroscopy. CONCLUSION: In FAI syndrome-a condition
      unknown to many clinicians (including medical)-chiropractors can play an
      important role in its diagnosis and referral for appropriate management.

PMID- 20808617
TI  - Trigeminal neuralgia and chiropractic care: a case report.
AB  - The following case describes a 68 year-old woman with a 7(1/2) year history of
      worsening head and neck pain diagnosed as trigeminal neuralgia following surgical
      resection of a brain tumor. After years of unsuccessful management with
      medication and physical therapies, a therapeutic trial of chiropractic was
      carried out. Chiropractic care included ultrasound, manual therapies
      (manipulation and mobilization), soft tissue therapies, and home stretching
      exercises. After an initial treatment period followed by 18 months of supportive
      care the patient reported satisfactory improvement. It became evident that there
      were at least three sources of her symptoms: mechanical and/or degenerative neck
      pain, temporomandibular joint syndrome, and trigeminal neuralgia. While never
      completely pain-free, the patient continued to report that her pains reduced to
      minimal at times. At the most recent follow-up, the pain had not returned to pre
      treatment intractable levels. This case study demonstrates the importance of
      diagnosing and treating multiple sources of pain and the positive role
      chiropractic care can have in the management of patients with these clinical
      conditions. The potential for convergence of sensory input from the upper three
      cervical segments and the trigeminal nerve via the trigeminocervical nucleus is
      discussed.

PMID- 20808618
TI  - The West Family Chiropractic Dynasty: celebrating a century of accomplishment in
      Canada: Part I: Archibald B. West, DC, Samuel H. West, DC and Stephen E. West,
      DC: The Founding Father, his Son and Grandson.
AB  - This historical treatise documents the unbroken legacy of the West family of
      chiropractors which has flourished in Canada for over 100 years. Part I, unearths
      the origins, development and careers of Archibald West, the founder of this
      dynasty, his son Samuel and grandson Stephen. Part II, not yet ready for
      publication, will delve into the lives of Archibald's brother Samson and his
      chiropractic progeny, as well as a nephew of Stephen and another relative of
      Frederick West.

PMID- 20808619
TI  - Letters to the editor.

PMID- 20808620
TI  - Letters to the editor.

PMID- 20808621
TI  - Are we shy of clinical research in India?

PMID- 20808622
TI  - Emergency balloon dilation or stenting of critical coarctation of aorta in
      newborns and infants: An effective interim palliation.
AB  - BACKGROUND: Management of native uncomplicated coarctation in neonates remains
      controversial with current evidence favoring surgery. The logistics of organizing
      surgical repair at short notice in sick infants with critical coarctation can be
      challenging. METHODS AND RESULTS: We reviewed data of 10 infants (mean age of 2.9
      +/-1.6 weeks) who underwent catheter intervention for severe coarctation and left
      ventricular (LV) dysfunction between July 2003 and August 2007. Additional
      cardiac lesions were present in 7. Mean systolic gradient declined from 51+/-12
      mm Hg to 8.7+/-6.7 mm Hg after dilation. The coarctation segment was stented in
      five patients. Procedural success was achieved in all patients with no mortality.
      Complications included brief cardiopulmonary arrest (n =1), sepsis (n = 1) and
      temporary pulse loss (n = 2). LV dysfunction improved in all patients. Average
      ICU stay was 5+/-3.4 days and hospital stay was 6.5+/-3.4 days. On follow-up
      (14.1+/-10.5 months), all developed restenosis after median period of 12 weeks
      (range four to 28 weeks). Three (two with stents) underwent elective coarctation
      repair, two underwent ventricular septal defect (VSD) closure and coarctation
      repair and one underwent pulmonary artery (PA) banding. Two patients who
      developed restenosis on follow-up were advised surgery, but did not report. Two
      (one with stent) underwent redilatation and are being followed with no
      significant residual gradients. CONCLUSION: Balloon dilation +/- stenting is an
      effective interim palliation for infants and newborns with critical coarctation
      and LV dysfunction. Restenosis is inevitable and requires to be addressed.

PMID- 20808623
TI  - Transcatheter interventions in critically ill neonates and infants with aortic
      coarctation.

PMID- 20808624
TI  - Role of prophylactic surgical ligation of patent ductus arteriosus in extremely
      low birth weight infants: Systematic review and implications for clinical
      practice.
AB  - OBJECTIVES: To investigate the effectiveness and safety of prophylactic surgical
      ligation of patent ductus arteriosus (PDA) on mortality and morbidity of preterm
      infants weighing less than 1000 g at birth. MATERIALS AND METHODS: The study
      conducted a systematic search of available database from 1996-2008. Retrieved
      articles were assessed for eligibility and data was abstracted independently by
      two reviewers. Decisions to include studies for review and the methodological
      quality of included studies were asssessed in duplicate based on predetermined
      criteria. No language restrictions were applied. RESULTS: Only one eligible study
      that enrolled 84 extremely low birth weight infants was identified. Prophylactic
      surgical ligation of PDA resulted in a statistically significant reduction of
      severe stage II or III necrotizing enterocolitis, [RR 0.25, 95% CI (0.08, 0.83),
      P value 0.02, number needed to treat 5]. The study, however, found no
      statistically significant difference in mortality, intraventricular hemorrhage,
      bronchopulmonary dysplasia, and retinopathy of prematurity. CONCLUSIONS: Current
      evidence does not support the use of prophylactic surgical ligation of PDA in the
      management of the preterm infants.

PMID- 20808625
TI  - Role of myocardial perfusion single photon emission computed tomography in
      pediatric cardiology practice.
AB  - Diagnostic and prognostic power of myocardial perfusion imaging in patients with
      coronary artery disease has been demonstrated with planar imaging which was
      further improvised with addition of gated SPECT and newer Technetium labeled
      myocardial perfusion tracers like SestaMIBI, Tetrofosmin. Myocardial perfusion
      abnormalities at rest and after stress are considered to be the best predictors
      of cardiac event-free survival in adults with ischemic heart disease. This
      article highlights various myocardial perfusion imaging (MPI)
      radiopharmaceuticals, exercise procedures, pharmacological stress protocols,
      indications for MPI and myocardial perfusion patterns in children with some of
      the common congenital and acquired heart diseases.

PMID- 20808626
TI  - Teamwork in pediatric heart care.
AB  - Pediatric cardiac specialties, pediatric cardiology (pediatric cardiac surgery
      and pediatric cardiac anesthesiology and intensive care) are only now being
      recognized as distinct specialties in most parts of the world. There has been a
      tremendous growth in knowledge in these specialties in the last 30-40 years with
      dramatic improvements in outcome.Pediatric cardiac care thrives on team work. The
      cohesiveness of the team of caregivers has a direct impact on the patient
      outcomes and efficiency of the system. The development of hybrid heart procedures
      in pediatric heart care represents an important benchmark in a team-based
      approach to patient care where a group of specialists with specific skills work
      closely together for ensuring the best possible patient outcome. Establishment of
      a cohesive team requires organization of group of team members with diverse
      skills to come together through good mutual understanding, under a leadership
      that actively promotes team harmony. Excellent communication among team members
      is a core requirement. The barriers for development and sustenance of a
      successful team must be recognized and overcome. They include egos of key team
      members as a source of conflict, time for interactions, disproportionate rewards
      and recognition for members of the team and traditional hierarchical
      arrangements. Special attention must be paid to motivating non-physician staff.

PMID- 20808627
TI  - Musings on a quarter of a century in pediatric cardiac technology.

PMID- 20808628
TI  - Digoxin in management of heart failure in children: Should it be continued or
      relegated to the history books?

PMID- 20808629
TI  - Supracardiac anomalous pulmonary venous connection with unilateral pulmonary
      venous atresia: Diagnosis and management.
AB  - We report a case of a 6-day-old neonate referred to us for surgical correction of
      total anomalous pulmonary venous connection. Meticulous evaluation contributed to
      accurate diagnosis of associated unilateral pulmonary venous atresia. This unique
      association provides insights into the importance of evaluation of all pulmonary
      veins using various imaging tools.

PMID- 20808630
TI  - Radiofrequency ablation in an infant with recurrent supraventricular tachycardia
      and cyanosis.
AB  - We report an unusual presentation of supraventricular tachycardia, in an infant,
      with cyanosis. The child had atrial septal defect with hypoplastic right
      ventricle. Radiofrequency ablation was performed in view of drug resistant SVT.

PMID- 20808631
TI  - Transcatheter closure of patent ductus arteriosus and interruption of inferior
      vena cava with azygous continuation using an Amplatzer duct occluder II.
AB  - We report a case of transcatheter closure of patent ductus arteriosus using the
      new Amplatzer duct occluder II in an adult patient with interrupted inferior vena
      cava with azygous continuation via the femoral artery approach.

PMID- 20808632
TI  - Percutaneous closure of patent ductus arteriosus via internal jugular vein in
      patient with interrupted inferior vena cava.
AB  - Transcatheter closure of patent ductus arteriosus (PDA) using various occluders
      and coils via femoral vein is a well established therapeutic option. However, in
      patients with interrupted inferior vena cava (IVC) it is not feasible to close
      the PDA percutaneously using traditional methods. We present a nine-year-old girl
      with IVC interruption in whom percutaneous closure of PDA was successfully
      accomplished via the transjugular approach.

PMID- 20808633
TI  - Williams syndrome and Ebstein's anomaly: A rare association.
AB  - We report a rare case of Williams syndrome associated with Ebstein's anomaly of
      the tricuspid valve. To our knowledge, such an association has never been
      reported.

PMID- 20808634
TI  - Renal artery stenosis due to neurofibromatosis.
AB  - A 4-year-old boy with hypertension due to renal artery stenosis and
      neurofibromatosis type 1 is presented for its rarity. Renal artery stenosis due
      to neurofibromatosis is underrecognized and may masquerade Takayasu's arteritis
      in Asian children.

PMID- 20808635
TI  - Candida krusei infection presenting as a right ventricular mass in a two month
      old Infant.
AB  - The prevalence of fungal infections in newborns and small infants is on the rise
      consequent to the improved care and survival of preterm babies. Most of these
      premature infants are immunocompromised and subjected to invasive monitoring and
      therapy in neonatal intensive care units making them susceptible to nosocomial
      infections. We report a rare case of right ventricular mass secondary to candida
      krusei infection which was excised surgically. This article reemphasizes the
      importance of stringent aseptic practices in neonatal intensive care units to
      prevent nosocomial infections and the early use of echocardiography in neonates
      presenting with atypical unexplained symptoms to hasten diagnosis and facilitate
      timely intervention.

PMID- 20808636
TI  - Use of Bosentan in neonatal post cardiac surgery pulmonary hypertension.
AB  - We report the use of Bosentan in the post-operative period of a neonate with
      obstructed infradiaphragmatic total anomalous pulmonary venous connection and
      severe pulmonary arterial hypertension. To our knowledge, this is the first
      report of use of Bosentan in this situation.

PMID- 20808637
TI  - Flash pulmonary edema in a post arterial switch operation - High flow oxygen as a
      treatment modality.
AB  - We report a case of a 3-year-old boy who underwent an arterial switch operation
      with relief of left ventricular outflow tract obstruction and later presented
      with recurrent episodes of flash pulmonary edema. High-flow humidified oxygen
      with positive pressure support (Vapotherm) was used as a treatment modality,
      thereby avoiding intubation and mechanical ventilation.

PMID- 20808638
TI  - Pulmonary arteriovenous malformations after cavopulmonary anastomosis.
AB  - Pulmonary arteriovenous malformation (PAVM) is common after cavopulmonary
      anastomosis. PAVMs appear on chest X-ray film as diffuse opacity in one or both
      lungs. Angiographically, it appears as spidery diffuse vascularity with near
      simultaneous opacification of pulmonary arteries and veins.

PMID- 20808639
TI  - Comparative analysis of techniques to purify plasma membrane proteins.
AB  - The aim of this project was to identify the best method for the enrichment of
      plasma membrane (PM) proteins for proteomics experiments. Following tryptic
      digestion and extended liquid chromatography-tandem mass spectrometry
      acquisitions, data were processed using MaxQuant and Gene Ontology (GO) terms
      used to determine protein subcellular localization. The following techniques were
      examined for the total number and percentage purity of PM proteins identified:
      (a) whole cell lysate (total number, 84-112; percentage purity, 9-13%); (b) crude
      membrane preparation (104-111; 17-20%); (c) biotinylation of surface proteins
      with N-hydroxysulfosuccinimydyl-S,S-biotin and streptavidin pulldown (78-115; 27
      31%); (d) biotinylation of surface glycoproteins with biocytin hydrazide and
      streptavidin pulldown (41-54; 59-85%); or (e) biotinylation of surface
      glycoproteins with amino-oxy-biotin (which labels the sialylated fraction of PM
      glycoproteins) and streptavidin pulldown (120; 65%). A two- to threefold increase
      in the overall number of proteins identified was achieved by using stop and go
      extraction tip (StageTip)-based anion exchange (SAX) fractionation. Combining
      technique (e) with SAX fractionation increased the number of proteins identified
      to 281 (54%). Analysis of GO terms describing these proteins identified a large
      subset of proteins integral to the membrane with no subcellular assignment. These
      are likely to be of PM location and bring the total PM protein identifications to
      364 (68%). This study suggests that selective biotinylation of the cell surface
      using amino-oxy-biotin in combination with SAX fractionation is a useful method
      for identification of sialylated PM proteins.

PMID- 20808640
TI  - An accurate and clean calibration method for MALDI-MS.
AB  - A new method for the mass calibration of the matrix-assisted laser
      desorption/ionization-mass spectrometry spectrum is introduced. This method
      achieves the same accuracy as that of internal calibration but without its
      drawbacks. The interference and signal suppression by calibration standard are
      avoided, and a pure/clean sample spectrum is obtained. No prior knowledge about
      the sample quantity is required for the calibration. The effectiveness of the
      method is demonstrated with protein identification data.

PMID- 20808641
TI  - Laser capture microdissection in the tissue biorepository.
AB  - An important need of many cancer research projects is the availability of high
      quality, appropriately selected tissue. Tissue biorepositories are organized to
      collect, process, store, and distribute samples of tumor and normal tissue for
      further use in fundamental and translational cancer research. This, in turn,
      provides investigators with an invaluable resource of appropriately examined and
      characterized tissue specimens and linked patient information. Human tissues, in
      particular, tumor tissues, are complex structures composed of heterogeneous
      mixtures of morphologically and functionally distinct cell types. It is essential
      to analyze specific cell types to identify and define accurately the biologically
      important processes in pathologic lesions. Laser capture microdissection (LCM) is
      state-of-the-art technology that provides the scientific community with a rapid
      and reliable method to isolate a homogeneous population of cells from
      heterogeneous tissue specimens, thus providing investigators with the ability to
      analyze DNA, RNA, and protein accurately from pure populations of cells. This is
      particularly well-suited for tumor cell isolation, which can be captured from
      complex tissue samples. The combination of LCM and a tissue biorepository offers
      a comprehensive means by which researchers can use valuable human biospecimens
      and cutting-edge technology to facilitate basic, translational, and clinical
      research. This review provides an overview of LCM technology with an emphasis on
      the applications of LCM in the setting of a tissue biorepository, based on the
      author's extensive experience in LCM procedures acquired at Fox Chase Cancer
      Center and Hollings Cancer Center.

PMID- 20808642
TI  - Multi-sample pooling and illumina genome analyzer sequencing methods to determine
      gene sequence variation for database development.
AB  - Determination of sequence variation within a genetic locus to develop clinically
      relevant databases is critical for molecular assay design and clinical test
      interpretation, so multisample pooling for Illumina genome analyzer (GA)
      sequencing was investigated using the RET proto-oncogene as a model. Samples were
      Sanger-sequenced for RET exons 10, 11, and 13-16. Ten samples with 13 known
      unique variants ("singleton variants" within the pool) and seven common changes
      were amplified and then equimolar-pooled before sequencing on a single flow cell
      lane, generating 36 base reads. For comparison, a single "control" sample was run
      in a different lane. After alignment, a 24-base quality score-screening threshold
      and 3; read end trimming of three bases yielded low background error rates with a
      27% decrease in aligned read coverage. Sequencing data were evaluated using an
      established variant detection method (percent variant reads), by the presented
      subtractive correction method, and with SNPSeeker software. In total, 41 variants
      (of which 23 were singleton variants) were detected in the 10 pool data, which
      included all Sanger-identified variants. The 23 singleton variants were detected
      near the expected 5% allele frequency (average 5.17%+/-0.90% variant reads), well
      above the highest background error (1.25%). Based on background error rates, read
      coverage, simulated 30, 40, and 50 sample pool data, expected singleton allele
      frequencies within pools, and variant detection methods; >or=30 samples (which
      demonstrated a minimum 1% variant reads for singletons) could be pooled to
      reliably detect singleton variants by GA sequencing.

PMID- 20808643
TI  - Comparison between NuGEN's WT-Ovation Pico and one-direct amplification systems.
AB  - Differential gene expression between groups of homogenous cell types is a
      biological question whose time has come. RNA can be extracted from small numbers
      of cells, such as those isolated by laser-capture microdissection, but the small
      amounts obtained often require amplification to enable whole genome transcriptome
      profiling by technologies such as microarray analysis and RNA-seq. Recently,
      advances in amplification procedures make amplification directly from whole cell
      lysates possible. The aim of this study was to compare two amplification systems
      for variations in observed RNA abundance attributable to the amplification
      procedure for use with small quantities of cells isolated by laser-capture
      microdissection. Arabidopsis root cells undergoing giant cell formation as a
      result of nematode infestation and uninfested control root cells were laser
      captured and used to evaluate two amplification systems. One, NuGEN's WT-Ovation
      Pico (Pico) amplification system, uses total RNA as starting material, and the
      other, NuGEN's WT-One-Direct (One-Direct) amplification system, uses lysate
      containing the captured cells. The reproducibility of whole genome transcript
      profiling and correlations of both systems were investigated after microarray
      analysis. The One-Direct system was less reproducible and more variable than the
      Pico system. The Pico amplification kit resulted in the detection of thousands of
      differentially expressed genes between giant cells and control cells. This is in
      marked contrast to the relatively few genes detected after amplification with the
      One-Direct amplification kit.

PMID- 20808644
TI  - A comparative study of in-gel digestions using microwave and pressure-accelerated
      technologies.
AB  - One of the most popular methods to prepare tryptic peptides for bottom-up
      proteomic analysis is in-gel digestion. To date, there have been few studies
      comparing various digestion methods. In this study, we compare the efficiency of
      several popular in-gel digestion methods, along with new technologies that may
      improve digestion efficiency, using a human epidermoid carcinoma cell lysate
      protein standard. The efficiency of each protocol was based on the average number
      of proteins identified and their respective sequence coverage and relative
      quantitation using spectral counting. The importance of this study lies in its
      comparison of pre-existing in-gel digestion methods with those that use newly
      developed technologies that may introduce the potential for a more cost-effective
      digestion, higher protein yield, and an overall reduction in processing time. The
      following four protocols were compared: an overnight in-gel digestion protocol;
      an overnight in-gel digestion protocol, in which we remove the vacuum
      centrifugation steps; in-gel digestion in a barometric pressure cycler; and in
      gel digestion in a scientific microwave. Several variables were tested for
      increased digestion efficiency and decreased keratin contamination. Statistical
      analysis was performed on replicate samples to determine significant differences
      between protocols.

PMID- 20808646
TI  - Management in Indian blood banking system: True reality.

PMID- 20808647
TI  - Bedside practice of blood transfusion in a large teaching hospital in Uganda: An
      observational study.
AB  - BACKGROUND: Adverse transfusion reactions can cause morbidity and death to
      patients who receive a blood transfusion. Blood transfusion practice in Mulago
      Hospital, Kampala, Uganda is analyzed to see if and when these practices play a
      role in the morbidity and mortality of patients. MATERIALS AND METHODS: An
      observational study on three wards of Mulago Hospital. Physicians, paramedics,
      nurses, medical students and nurse students were observed using two
      questionnaires. For comparison, a limited observational study was performed in
      the University Medical Centre Groningen (UMCG) in Groningen, The Netherlands.
      RESULTS: In Mulago Hospital guidelines for blood transfusion practice were not
      easily available. Medical staff members work on individual professional levels.
      Students perform poorly due to inconsistency in their supervision. Documentation
      of blood transfusion in patient files is scarce. There is no immediate bedside
      observation, so transfusion reactions and obstructions in the blood transfusion
      flow are not observed. CONCLUSION: The poor blood transfusion practice is likely
      to play a role in the morbidity and mortality of patients who receive a blood
      transfusion. There is a need for a blood transfusion policy and current practical
      guidelines.

PMID- 20808648
TI  - Quality evaluation of four hemoglobin screening methods in a blood donor setting
      along with their comparative cost analysis in an Indian scenario.
AB  - BACKGROUND: Despite the wide range of methods available for measurement of
      hemoglobin, no single technique has emerged as the most appropriate and ideal for
      a blood donation setup. MATERIALS AND METHODS: A prospective study utilizing 1014
      blood samples was carried out in a blood donation setting for quality evaluation
      of four methods of hemoglobin estimation along with cost analysis: Hematology
      cell analyzer (reference), HCS, CuSO4 method and HemoCue. RESULTS: Mean value of
      HemoCue (mean +/- SD = 14.7 +/- 1.49 g/dl) was higher by 0.24 compared to
      reference (mean +/- SD = 13.8 +/- 1.52 g/dl) but not statistically significant (
      P > 0.05). HemoCue proved to be the best technique (sensitivity 99.4% and
      specificity 84.4%) whereas HCS was most subjective with 25.2% incorrect
      estimations. CuSO4 proved to be good with 7.9% false results. Comparative cost
      analysis of each method was calculated to be 35 INR/test for HemoCue, 0.76 INR
      /test for HCS and 0.06-0.08 INR /test for CuSO4. CONCLUSION: CuSO4 method gives
      accurate results, if strict quality control is applied. HemoCue is too expensive
      to be used as a primary screening method in an economically restricted country
      like India.

PMID- 20808649
TI  - Hyperbilirubinemia in normal healthy donors.
AB  - The present study was carried out in B.A.R.C. Hospital Blood Bank over a span of
      five years, and includes 2734 donors. All the bags were screened for HIV, HBsAg,
      HCV and VDRL and the plasma in the pilot tubes of the blood bags was observed to
      detect any abnormality in color. In 27 cases plasma was found to be icteric and
      liver function tests were carried out on these samples. Two donors showed higher
      SGPT level, and were excluded. No significant increases in liver enzymes were
      recorded in the others. Causes of icteric plasma in these apparently healthy
      donors are discussed. Differential diagnosis includes Gilbert's disease,
      hemolytic anemia, drug-induced anemia and other hepatic causes of
      hyperbilirubinemia, of which Gilbert's disease is most probable cause with a
      prevalence of 0.91% in our population. As there are no studies to document the
      safety of the recipients receiving such abnormal colored plasma as well as to
      document the hazards in its transfusion, the question arises whether to transfuse
      such units or not. This study highlights this dilemma. A reassessment of existing
      policies and regulations is merited.

PMID- 20808650
TI  - Comparison of plateletpheresis on three continuous flow cell separators.
AB  - INTRODUCTION: Platelet concentrate (PC) remains one of the most important support
      measures in thrombocytopenic patients. An efficient cell separator is a
      prerequisite for an optimally functioning apheresis setup. Donor blood count may
      undergo a temporary reduction after the procedure. AIM: The aim was to find the
      extent of reduction in donor blood count (hemoglobin, hematocrit, white blood
      cell, and platelet) after plateletpheresis and to evaluate the cell separator for
      collection efficiency, processing time, and leukoreduction. STUDY DESIGN AND
      METHODS: Two hundred and thirty seven procedures performed on the Amicus (N =
      121), Fenwal CS-3000 Plus (N = 50) and Cobe spectra (N = 66) in a one year period
      were evaluated. The procedures performed on the continuous flow centrifugation
      (CFC) cell separators and donor blood counts (pre and post donation) done were
      included in the study. RESULTS: The percent reduction in hemoglobin (HB),
      hematocrit (HCT), white blood cell (WBC) and platelet count ((PLT ct) was 2.9,
      3.1, 9, 30.7 (Mean, N = 237) respectively after the procedure. The post donation
      PLT ct reduced to < 100x109/L (range 80-100) in five donors (N = 5/237, Amicus).
      The pre donation PLT ct in them was 150-200x109/L. Collection efficiency
      (percent) of Amicus (79.3) was better as compared to the other two machines (CS:
      62.5, Cobe: 57.5). PC collected on Cobe spectra had <1x106 WBC. The donor pre
      donation PLT levels had a positive correlation to the product PLT yield (r =
      0.30, P = 0.000). CONCLUSION: Monitoring donor blood counts helps to avoid
      pheresis induced adverse events. A cautious approach is necessary in donors whose
      pre donation PLT ct is 150-200x109/L. The main variable in PLT yield is donor PLT
      ct (pre donation). High collection efficiency is a direct measure of an optimally
      functioning cell separator.

PMID- 20808651
TI  - Evaluation of knowledge of healthcare workers in hospitals of Zabol city on
      proper methods of blood and components transfusion.
AB  - BACKGROUND AND AIMS: Blood and components are more frequently used in surgery and
      non-surgical procedures. In medical procedures blood transfusion is important and
      needs adequate expertise and practice, thus adequate knowledge in healthcare
      workers of this procedure is essential. MATERIALS AND METHODS: This descriptive
      study is designed to assess the knowledge of healthcare workers about proper
      methods of blood transfusion, and how to promote their knowledge for proper
      performance if their knowledge is inadequate. Data were collected with aimed
      questionnaire and analyzed by statistics software. RESULT: The study population
      mainly comprised 122 healthcare workers (HCWs). The main findings from this study
      showed that 26.2% of healthcare workers (HCWs) had low-level knowledge, 22.1%
      moderate and 51.6% acceptable knowledge. We did not find any significant
      correlation between knowledge of HCWs and years in profession, participation in
      training, number of blood transfusions per day, age, gender, etc. (P < 0.05).
      DISCUSSION AND CONCLUSION: Results strongly emphasized the need for a curriculum
      to promote knowledge of HCWs about blood transfusion because we found low and
      moderate level of knowledge in approximately half our samples and on the
      importance of blood transfusion procedure, suggesting that more attempts should
      be made to build up knowledge about blood transfusion.

PMID- 20808652
TI  - Use of blood components in critically ill patients in the medical intensive care
      unit of a tertiary care hospital.
AB  - BACKGROUND: The art of fluid administration and hemodynamic support is one of the
      most challenging aspects of treating critically ill patients. Transfusions of
      blood products continue to be an important technique for resuscitating patients
      in the intensive care settings. Concerns about the rate of inappropriate
      transfusion exist, particularly given the recognized risks of transfusions and
      the decreasing availability of donor blood. We investigated the current
      transfusion practice in the critically ill patients at our hospital. MATERIALS
      AND METHODS: A total of 1817 consecutive critically ill patients admitted between
      January 2006 and December 2006 were included in this retrospective study. The
      blood request forms of the patients were analyzed, and their pretransfusion
      investigations, indications for transfusions, etc. were studied. RESULTS: Nine
      hundred and eleven (50.1%) critically ill patients, comprising 71.6% males and
      28.4% females, received blood/blood components. About 43.8% patients were
      administered packed red cells (PRC), 18.27% fresh frozen plasma (FFP) and 8.4%
      transfused platelets. Among those receiving PRC, 31.1% had a pretransfusion Hb
      below 7.5g%, 34.4% had Hb between 7.5 and 9g%, while 21.4% had Hb above 9g%.
      Among those receiving FFP, 14.5% had an international normalized ratio INR < 1.5,
      and 19% had a pretransfusion platelet count above 50,000/cumm. During the study,
      there were 7% of the patients who received red cells and FFP, 2% of the patients
      received red cells and platelets, 1% of the patients received platelets and FFP,
      and 5% of the patients had received all the three components, i.e., red cells,
      FFP and Platelets. The baseline investigations and/or clinical indications were
      not mentioned in 13.1% of patients receiving PRC, 57% receiving FFP and 49.7%
      receiving platelets. CONCLUSION: About 21.4% of PRC, 14.5% of FFP, and 19% of
      platelets were inappropriately indicated. Clinicians in our centre were
      conservative in keeping with recent transfusion guidelines. A significant number
      of blood request forms were still incomplete with baseline investigations not
      mentioned in the request forms.

PMID- 20808653
TI  - Quality assessment of platelet concentrates prepared by platelet rich plasma
      platelet concentrate, buffy coat poor-platelet concentrate (BC-PC) and apheresis
      PC methods.
AB  - BACKGROUND: Platelet rich plasma-platelet concentrate (PRP-PC), buffy coat poor
      platelet concentrate (BC-PC), and apheresis-PC were prepared and their quality
      parameters were assessed. STUDY DESIGN: IN THIS STUDY, THE FOLLOWING PLATELET
      PRODUCTS WERE PREPARED: from random donor platelets (i) platelet rich plasma -
      platelet concentrate (PRP-PC), and (ii) buffy coat poor-platelet concentrate (BC
      PC) and (iii) single donor platelets (apheresis-PC) by different methods. Their
      quality was assessed using the following parameters: swirling, volume of the
      platelet concentrate, platelet count, WBC count and pH. RESULTS: A total of 146
      platelet concentrates (64 of PRP-PC, 62 of BC-PC and 20 of apheresis-PC) were
      enrolled in this study. The mean volume of PRP-PC, BC-PC and apheresis-PC was
      62.30+/-22.68 ml, 68.81+/-22.95 ml and 214.05+/-9.91 ml and ranged from 22-135
      ml, 32-133 ml and 200-251 ml respectively. The mean platelet count of PRP-PC, BC
      PC and apheresis-PC was 7.6+/-2.97 x 1010/unit, 7.3+/-2.98 x 1010/unit and 4.13+/
      1.32 x 1011/unit and ranged from 3.2 -16.2 x 1010/unit, 0.6-16.4 x 1010/unit and
      1.22-8.9 x 1011/unit respectively. The mean WBC count in PRP-PC (n = 10), BC-PC
      (n = 10) and apheresis-PC (n = 6) units was 4.05+/-0.48 x 107/unit, 2.08+/-0.39 x
      107/unit and 4.8+/-0.8 x 106/unit and ranged from 3.4 -4.77 x 107/unit, 1.6-2.7 x
      107/unit and 3.2 - 5.2 x 106/unit respectively. A total of 26 units were analyzed
      for pH changes. Out of these units, 10 each were PRP-PC and BC-PC and 6 units
      were apheresis-PC. Their mean pH was 6.7+/-0.26 (mean+/-SD) and ranged from 6.5 -
      7.0 and no difference was observed among all three types of platelet concentrate.
      CONCLUSION: PRP-PC and BC-PC units were comparable in terms of swirling, platelet
      count per unit and pH. As expected, we found WBC contamination to be less in BC
      PC than PRP-PC units. Variation in volume was more in BC-PC than PRP-PC units and
      this suggests that further standardization is required for preparation of BC-PC.
      As compared to the above two platelet concentrates, all the units of apheresis-PC
      fulfilled the desired quality control criteria of volume. Apheresis-PC units
      showed better swirling and platelet count than PRP-PCs and BC-PCs. All the
      platelet concentrates units had pH well above the recommended norm.

PMID- 20808654
TI  - Alloimmunization among transfusion-dependent thalassemia patients.
AB  - BACKGROUND: Thalassemia is a common hemoglobin disorder in Iran and one of the
      major public health problems. Although blood transfusions are lifesavers for
      thalassemia patients, they may be associated with some complications especially
      erythrocyte alloimmunization. The purpose of this study was to investigate the
      prevalence of red blood cell alloantibodies and to determine types of these
      antibodies among multiple-transfused thalassemic patients. MATERIALS AND METHODS:
      A total of 313 thalassemia patients in the northeast of Iran, who received
      regular blood transfusion, were included in this study. Screening of antibodies
      was performed on fresh serum of all patients and then antibodies were identified
      in patients' serum that had positive antibody screening test using a panel of
      recognized blood group antigens. RESULTS: We identified 12 alloantibodies in 9
      patients (2.87%) that all were against Rhesus (Rh) blood group antigens (D, C,
      E). Three patients developed 2 antibodies, and others had one antibody. The most
      common alloantibodies were Anti-D (88.88%) and followed by Anti-C and Anti-E.
      Higher frequency of alloimmunization was observed in female, Rh negative and
      splenectomized patients. CONCLUSION: This study showed that evaluation of the
      packed cells for Rh (C, E) from the start of transfusion can be helpful in
      decreasing the rate of alloantibody synthesis.

PMID- 20808655
TI  - Comparing prevalence of Iron Deficiency Anemia and Beta Thalassemia Trait in
      microcytic and non-microcytic blood donors: suggested algorithm for donor
      screening.
AB  - BACKGROUND: The prevalence of microcytosis in donors and Iron Deficiency Anemia
      (IDA) and Beta-Thalassemia trait (BTT) in microcytic and non-microcytic donors
      has not been studied in India. The present study aims at finding the same.
      MATERIALS AND METHODS: Initially 925 donor samples were evaluated on cell
      counter. Of these, 50 were found to be microcytic. These were subjected to
      Ferritin and HbA2 determination. Subsequently, an additional 51, age-and-sex
      matched non-microcytic donor samples were selected to serve as controls. These
      were subjected to the same tests. RESULTS: The prevalence of microcytosis was
      5.4% (50/925). Among the microcytic donors, 52% were IDA, 36% BTT, 8% both, and
      4% none. In case of non-microcytic donors 29.4% were IDA, 3.9% BTT, and 66.7%
      none. CONCLUSIONS: The study revealed a high prevalence of IDA and BTT in blood
      donors and a higher probability of finding these in the microcytic samples. This
      prompted authors to suggest an algorithm for screening of blood donors for IDA
      and BTT. The algorithm recommends doing an hemogram on all donor samples,
      routinely. Ferritin could be done only in microcytic samples. At levels lower
      than15 ng/ml, it is diagnosed as IDA, and therefore, HPLC is performed only for
      non-IDA samples with Ferritin levels higher than 15 ng/ml. By employing this
      algorithm, a substantial number of IDA and BTT could be diagnosed while keeping
      the number of Ferritin tests small and the number of HPLC tests even smaller and
      thus making it cost efficient.

PMID- 20808657
TI  - Blood transfusion services in Bangladesh.

PMID- 20808656
TI  - The evolution of immunohematology in South Asian countries.
AB  - Many factors have resulted in the slow development of transfusion services in
      some South Asian countries. Despite difficulties, there have been some excellent
      developments and the outlook for the future is very positive. The biggest
      problems relate to the availability of the truly voluntary altruistic blood
      donors and considerable work is still needed to upgrade this aspect of the work.
      Screening for transfusion transmissible diseases is now widespread although there
      is still a requirement to enhance quality assurance procedures and to improve
      statistical definitions and collection. Other factors that have affected the
      evolution of immunohematology are outlined and there is now optimism for the
      future.

PMID- 20808658
TI  - Attitude and willingness toward blood donation in Iranian students.

PMID- 20808659
TI  - Environmental concerns and climate change: Need for proactive participation.

PMID- 20808660
TI  - Understanding the mechanism of toxicity of carbon nanoparticles in humans in the
      new millennium: A systemic review.
AB  - Manmade nanoparticles range from the well-established multi-ton production of
      carbon black and fumed silica for applications in plastic fillers and car tyres
      to microgram quantities of fluorescent quantum dots used as markers in biological
      imaging. While benefits of nanotechnology are widely publicized, the discussion
      of the potential effects of their widespread use in the consumer and industrial
      products are just beginning to emerge. Acceptance of nanoparticle toxicity led to
      wide acceptance of the fact that nanotoxicology, as a scientific discipline shall
      be quite different from occupational hygiene in approach and context.
      Understanding the toxicity of nanomaterials and nano-enabled products is
      important for human and environmental health and safety as well as public
      acceptance. Assessing the state of knowledge about nanotoxicology is an important
      step in promoting comprehensive understanding of the health and environmental
      implications of these new materials. Very limited data exist for health effects
      secondary to inhalation of very fine respirable particles in the occupational
      environment. Nanomaterials may have effects on health due to their size, surface,
      shape, charge, or other factors, which are not directly predictable from mass
      concentration measurements. Numerous epidemiological studies have associated
      exposure to small particles such as combustion-generated fine particles with lung
      cancer, heart disease, asthma and/or increased mortality. The omnipresence of
      nanoparticles shifts focus of research toward efforts to mitigate the health
      effects of nanoparticles. Newer health assessment methods and newer techniques
      need to be developed for diagnosing sub-optimal health in populations exposed to
      carbon nanoparticles.

PMID- 20808661
TI  - High-altitude medicine.
AB  - Sojourns to high altitude have become common for recreation and adventure
      purposes. In most individuals, gradual ascent to a high altitude leads to a
      series of adaptive changes in the body, termed as acclimatization. These include
      changes in the respiratory, cardiovascular, hematologic systems and cellular
      adaptations that enhance oxygen delivery to the tissues and augment oxygen
      uptake. Thus there is an increase in pulmonary ventilation, increase in diffusing
      capacity in the lung, an increase in the cardiac output and increase in the red
      blood cell count due to an increase in erythropoietin secretion by the kidney,
      all of which enhance oxygen delivery to the cells. Cellular changes like increase
      in the number of mitochondria and augmentation of cytochrome oxidase systems take
      months or years to develop. Too rapid an ascent or inability to acclimatize leads
      to high-altitude illnesses. These include acute mountain sickness (AMS), high
      altitude cerebral edema (HACE) and high-altitude pulmonary edema (HAPE). Acute
      mountain sickness is self limiting if recognized early. Both HACE and HAPE are
      life threatening and need to be treated aggressively. The key to treatment of
      these illnesses is early recognition; administration of supplemental oxygen; and
      descent if required. Drugs like acetazolamide, dexamethasone, nifedipine may be
      administered as recommended.

PMID- 20808662
TI  - The family and work connect: A case for relationship-focused family life
      education.
AB  - The article presents the premises for the need to develop a relationship-focused
      family life education program for young adult employees. The article explores the
      changing trends in the Indian family unit and their impact on the workforce. The
      author also presents the findings from interviews with family-intervention
      experts and their recommendations for the contents of such a program.

PMID- 20808663
TI  - Chronic mercury poisoning: Report of two siblings.
AB  - Mercury exists as organic inorganic and elementary forms in nature and is one of
      the most toxic metals that are poisonous for human beings. Mercury is commonly
      used in many different sectors of industry such as in insects formulas,
      agriculture products, lamps, batteries, paper, dyes, electrical/electronic
      devices, jewelry, and in dentistry. In this study, two siblings (one a 7-year-old
      boy and the other a 13 years old girl) are reported who developed chronic mercury
      poisoning as a result of long-term contact with batteries. Our aim is to
      emphasize the importance of mercury poisoning that is extremely rarely seen in
      childhood.

PMID- 20808664
TI  - Some initiative in e-waste disposal, management and recycling.

PMID- 20808665
TI  - Climate change and coastal mega cities of India.

PMID- 20808666
TI  - Aircraft maintenance and mesothelioma.

PMID- 20808667
TI  - Continuity of care for elderly patients with diabetes mellitus, hypertension,
      asthma, and chronic obstructive pulmonary disease in Korea.
AB  - We sought to assess continuity of care for elderly patients in Korea and to
      examine any association between continuity of care and health outcomes
      (hospitalization, emergency department visits, health care costs). This was a
      retrospective cohort study using the Korea National Health Insurance Claims
      Database. Elderly people, 65-84 yr of age, who were first diagnosed with diabetes
      mellitus (n=268,220), hypertension (n=858,927), asthma (n=129,550), or chronic
      obstructive pulmonary disease (COPD, n=131,512) in 2002 were followed up for four
      years, until 2006. The mean of the Continuity of Care Index was 0.735 for
      hypertension, 0.709 for diabetes mellitus, 0.700 for COPD, and 0.663 for asthma.
      As continuity of care increased, in all four diseases, the risks of
      hospitalization and emergency department visits decreased, as did health care
      costs. In the Korean health care system, elderly patients with greater continuity
      of care with health care providers had lower risks of hospital and emergency
      department use and lower health care costs. In conclusion, policy makers need to
      develop and try actively the program to improve the continuity of care in elderly
      patients with chronic diseases.

PMID- 20808668
TI  - Seroprevalence of tissue invading parasitic infections diagnosed by ELISA in
      Korea.
AB  - Seroprevalence of the IgG antibodies for Clonorchis sinensis, Paragonimus
      westermani, Taenia solium metacestode (cysticercus), and Spirometra erinacei
      plerocercoid (sparganum) was measured using enzyme-linked immunosorbent assay
      (ELISA) in sera of patients in Korea from 1993 to 2006. A total of 74,448
      specimens referred nationwide from 121 hospitals revealed an IgG positive rate of
      7.6% for the 4 parasites. The IgG positive rate (18.7%) for the 4 parasites in
      1993 decreased gradually to 6.6% in 2006. Individual positive rate decreased from
      5.2% (1993) to 1.6% (2006) for C. sinensis, from 2.8% (1993) to 1.1% (2006) for
      P. westermani, from 8.3% (1993) to 2.2% (2006) for cysticercus, and from 2.6%
      (1993) to 1.6% (2006) for sparganum. The positive rate was highest (21.2%) in the
      group of patients who ranged in age from 50-59 yr old, and in the group that was
      referred from the Seoul area (55.9%). In conclusion, our results suggest that
      tissue invading parasitic infections should always be included in differential
      diagnosis for patients with eosinophilia associated lesions of the central
      nervous system, liver, and lungs in Korea.

PMID- 20808669
TI  - Acute effects of intravenous administration of pamidronate in patients with
      osteoporosis.
AB  - We investigated acute effects of intermittent large dose bisphosphonate therapy
      in osteoporotic patients. Peripheral blood mononuclear cells were incubated with
      alendronate (100 microM) for 18 hr, in vitro and cytokine expressions were
      measured by real-time RT-PCR. Pamidronate 30 mg was administered on 26
      osteoporotic patients; and acute phase reactants, inflammatory cytokines and bone
      biomarkers were measured. The in vitro study showed significant increase in mRNA
      expression of IL-6, TNF-alpha and IFN-gamma. A notable rise in serum C-reactive
      protein (CRP) was observed over 3 days after pamidronate infusion (P=0.026).
      Serum levels of TNF-alpha, IL-6 and IFN-gamma were also significantly increased
      (P=0.009, 0.014, 0.035, respectively) and the increase in IL-6 levels were
      strongly correlated with CRP levels (P=0.04). Serum calcium and c-telopeptide
      levels rapidly decreased after the treatment (P=0.02, <0.001, respectively). This
      study showed that mRNA expression of inflammatory cytokines at peripheral blood
      mononuclear cells (PBMC) level were observed within 18 hr and marked elevation of
      inflammatory cytokines and acute phase reactants were demonstrated after
      pamidronate infusion at the dose for osteoporosis. Our studies confirmed that
      intermittent large dose aminobisphosphonate causes acute inflammation.

PMID- 20808670
TI  - Efficacy of dendritic cells matured early with OK-432 (Picibanil), prostaglandin
      E2, and interferon-alpha as a vaccine for a hormone refractory prostate cancer
      cell line.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil) was
      introduced as a potent stimulator of DC maturation in combination with
      prostaglandin-E(2) and interferon-alpha. We compared the efficacy of a DC
      prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and
      INF-alpha (OPA) with that of vaccines using other methods. On days 3 or 7 of DC
      culture, TNF-alpha (T), TNF-alpha and LPS (TL) or OPA were employed as maturation
      stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs
      using polyethyleneglycol. T cells were sensitized by the hybrids, and their
      proliferative and cytokine secretion activities and cytotoxicity were measured.
      The yields of early-mature DCs were higher, compared to yields at the
      conventional maturation time (P<0.05). In the early maturation setting, the mean
      fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%,
      18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated
      groups. The function of cytotoxic T cells, which were sensitized with the hybrids
      containing DCs matured early with OPA, was superior to that using other methods.
      The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early
      maturation with the OPA may be superior to that of the hybrids using conventional
      maturation methods.

PMID- 20808671
TI  - Prostate specific membrane antigen mRNA in blood as a potential predictor of
      biochemical recurrence after radical prostatectomy.
AB  - We investigated whether the detection of prostate specific membrane antigen
      (PSMA) in blood preoperatively has predictive value for biochemical recurrence
      (BCR) after radical prostatectomy in patients with prostate cancer. All 134
      patients scheduled to receive radical prostatectomy for prostate cancer were
      prospectively enrolled. The authors used nested reverse transcriptase-polymerase
      chain reaction (RT-PCR) assay to detect PSMA mRNA-bearing cells in peripheral
      blood, and analyzed the ability of PSMA mRNA positivity to predict BCR after
      surgery. PSMA-mRNA was detected in 24 (17.9%) patients by RT-PCR. Over a median
      follow-up of 20 months (range, 3 to 46 months), BCR developed in 15 patients
      (11.2%) and median time to BCR was 7 months (range, 3 to 25 months). Kaplan-Meier
      analysis revealed a significant difference between those positive or negative for
      PSMA in terms of recurrence-free actuarial probability (log rank P=0.0039).
      Multivariate analysis showed that positivity for PSMA mRNA (HR: 3.697, 95% CI
      1.285-10.634, P=0.015) and a biopsy Gleason score of >or=7 (HR: 4.500, 95% CI
      1.419-14.274, P=0.011) were independent preoperative predictors of BCR. The
      presence of PSMA mRNA in peripheral blood can be used to predict BCR after
      radical prostatectomy.

PMID- 20808672
TI  - Aldosterone modulates cell proliferation and apoptosis in the neonatal rat heart.
AB  - In the present study, we investigated whether and how the mineralocorticoid
      receptor antagonist spironolactone affects cardiac growth and development through
      apoptosis and cell proliferation in the neonatal rat heart. Newborn rat pups were
      treated with spironolactone (200 mg/kg/d) for 7 days. The cell proliferation was
      studied by PCNA immunostaining. The treatment with spironolactone decreased
      proliferating myocytes by 32% (P<0.05), and reduced myocytes apoptosis by 29%
      (P<0.05). Immunoblot and immunohistochemistry for the expression of p38, p53,
      clusterin, TGF-beta2, and extracellular signal-regulated kinase were performed.
      In the spironolactone group, p38, p53, clusterin, and TGF-beta2 protein
      expression was significantly decreased (P<0.05). These results indicate that
      aldosterone inhibition in the developing rat heart induces cardiac growth
      impairment by decreasing proliferation and apoptosis of myocytes.

PMID- 20808673
TI  - High dose vitamin D3 attenuates the hypocalciuric effect of thiazide in
      hypercalciuric rats.
AB  - Thiazide is known to decrease urinary calcium excretion. We hypothesized that
      thiazide shows different hypocalciuric effects depending on the stimuli causing
      hypercalciuria. The hypocalciuric effect of hydrochlorothiazide (HCTZ) and the
      expression of transient receptor potential vanilloid 5 (TRPV5), calbindin-D(28K),
      and several sodium transporters were assessed in hypercalciuric rats induced by
      high calcium diet and vitamin D(3). Urine calcium excretion and the expression of
      transporters were measured from 4 groups of Sprague-Dawley rats; control, HCTZ,
      high calcium-vitamin D, and high calcium-vitamin D with HCTZ groups. HCTZ
      decreased urinary calcium excretion by 51.4% in the HCTZ group and only 15% in
      the high calcium-vitamin D with HCTZ group. TRPV5 protein abundance was not
      changed by HCTZ in the high calcium-vitamin D with HCTZ group compared to the
      high calcium-vitamin D group. Protein abundance of NHE3, SGLT1, and NKCC2
      decreased in the hypercalciuric rats, and only SGLT1 protein abundance was
      increased by HCTZ in the hypercalciuric rats. The hypocalciuric effect of HCTZ is
      attenuated in high calcium and vitamin D-induced hypercalciuric rats. This
      attenuation seems to have resulted from the lack of HCTZ's effect on protein
      abundance of TRPV5 in severe hypercalciuric condition induced by high calcium and
      vitamin D.

PMID- 20808674
TI  - High peritoneal transport status is not an independent risk factor for high
      mortality in patients treated with automated peritoneal dialysis.
AB  - We undertook this study to elucidate whether baseline peritoneal membrane
      transport characteristics are associated with high mortality in incident
      automated peritoneal dialysis (APD) patients. This retrospective study includes
      117 patients who started APD at Yonsei University Health System from 1996 to 2008
      and had a PET within 3 months of APD initiation. High transporters were
      significantly older and had a higher incidence of cardiovascular disease. Patient
      survival for years 1, 3, and 5 were 85%, 64%, and 35% for high transporter and
      94%, 81%, and 68% for non-high transporter group (P<0.01). Multivariate analysis
      revealed that age, diabetes, cardiovascular disease, serum albumin level, and
      residual renal function were independently associated with high mortality in APD
      patients. In contrast, high transport status was not a significant predictor for
      mortality in this population when the other covariates were included. Even though
      high transport was significantly associated with mortality in the univariate
      analysis, its role seemed to be influenced by other comorbid conditions. These
      findings suggest that the proper management of these comorbid conditions, as well
      as appropriate ultrafiltration by use of APD and/or icodextrin, must be
      considered as protective strategies to improve survival in peritoneal dialysis
      patients with high transport.

PMID- 20808675
TI  - Differences in clinical characteristics between patients with non-erosive reflux
      disease and erosive esophagitis in Korea.
AB  - Gastroesophageal reflux disease (GERD) is caused by abnormal reflux of gastric
      contents into the esophagus. GERD can be divided into two groups, erosive
      esophagitis and non-erosive reflux disease (NERD). The aim of this study was to
      compare the clinical characteristics of patients with erosive esophagitis to
      those with NERD. All participating patients underwent an upper endoscopy during a
      voluntary health check-up. The NERD group consisted of 500 subjects with classic
      GERD symptoms in the absence of esophageal mucosal injury during upper endoscopy.
      The erosive esophagitis group consisted of 292 subjects with superficial
      esophageal erosions with or without typical symptoms of GERD. Among GERD
      patients, male gender, high body mass index, high obesity degree, high waist-to
      hip ratio, high triglycerides, alcohol intake, smoking and the presence of a
      hiatal hernia were positively related to the development of erosive esophagitis
      compared to NERD. In multivariated analysis, male gender, waist-to-hip ratio and
      the presence of a hiatal hernia were the significant risk factors of erosive
      esophagitis. We suggest that erosive esophagitis was more closely related to
      abdominal obesity.

PMID- 20808676
TI  - Clinical significance of colonic diverticulosis associated with bowel symptoms
      and colon polyp.
AB  - This study was done to evaluate prospectively the clinical significance of
      colonic diverticulosis. In the 1,030 consecutive outpatients undergoing
      colonoscopy, the information on the demographics, the patterns of bowel symptoms,
      and the prevalence of colon polyp were analyzed according to the presence of
      colonic diverticulosis. The mean age of 1,030 patients were 52.2 yr and 59.3%
      were male. The prevalence of diverticulosis was 19.7% (203/1,030). Of 203
      diverticulosis patients 85.2% were in proximal group, 5.4% in distal group and
      9.4% in both group. Six (3.0%) patients were found to have diverticulitis.
      Multivariate logistic regression analysis showed that an old age, diabetes and
      the presence of polyp were significant factors associated with proximal or both
      diverticulosis. A significant difference was demonstrated between the patients of
      distal diverticular group and the controls for the symptom frequency scores
      within the previous 4 weeks. The items, which showed difference, were hard stool,
      urgency, flatus, chest discomfort and frequent urination. In conclusion, old age,
      diabetes and the presence of colon polyp were associated with proximal
      diverticulosis. The temporal symptoms were more frequent in distal diverticulosis
      than in proximal diverticulosis in the study subjects.

PMID- 20808677
TI  - Stress-induced alterations in mast cell numbers and proteinase-activated receptor
      2 expression of the colon: role of corticotrophin-releasing factor.
AB  - This study was performed in order to assess whether acute stress can increase
      mast cell and enterochromaffin (EC) cell numbers, and proteinase-activated
      receptor-2 (PAR2) expression in the rat colon. In addition, we aimed to
      investigate the involvement of corticotrophin-releasing factor in these stress
      related alterations. Eighteen adult rats were divided into 3 experimental groups:
      1) a saline-pretreated non-stressed group, 2) a saline-pretreated stressed group,
      and 3) an astressin-pretreated stressed group. The numbers of mast cells, EC
      cells, and PAR2-positive cells were counted in 6 high power fields. In proximal
      colonic segments, mast cell numbers of stressed rats tended to be higher than
      those of non-stressed rats, and their PAR2-positive cell numbers were
      significantly higher than those of non-stressed rats. In distal colonic segments,
      mast cell numbers and PAR2-positive cell numbers of stressed rats were
      significantly higher than those of non-stressed rats. Mast cell and PAR2-positive
      cell numbers of astressin-pretreated stressed rats were significantly lower than
      those of saline-pretreated stressed rats. EC cell numbers did not differ among
      the three experimental groups. Acute stress in rats increases mast cell numbers
      and mucosal PAR2 expression in the colon. These stress-related alterations seem
      to be mediated by release of corticotrophin-releasing factor.

PMID- 20808678
TI  - Dexrazoxane for preventing anthracycline cardiotoxicity in children with solid
      tumors.
AB  - This study attempted to assess the incidence and outcome of anthracycline
      cardiotoxicity and the role of dexrazoxane as a cardioprotectant in childhood
      solid tumors. The dexrazoxane group included 47 patients and the control group of
      historical cohort included 42. Dexrazoxane was given in the 10:1 ratio to
      doxorubicin. Fractional shortening and systolic and diastolic left ventricular
      diameters were used to assess the cardiac function. The median follow-ups were 54
      months in the dexrazoxane group and 86 months in the control group. The mean
      cumulative doses of doxorubicin were 280.8+/-83.4 mg/m(2) in the dexrazoxane
      group and 266.1+/-75.0 mg/m(2) in the control group. The dexrazoxane group
      experienced significantly fewer cardiac events (27.7% vs. 52.4%) and less severe
      congestive heart failure (6.4% vs. 14.3%) than the control group. Thirteen
      cardiotoxicities including one cardiac death and 2 congestive heart failures
      occurred in the dexrazoxane group, and 22 cardiotoxicities including 2 cardiac
      deaths and 4 congestive heart failures, in the control group. Five year cardiac
      event free survival rates were 69.2% in the dexrazoxane group and 45.8% in the
      control group (P=0.04). Dexrazoxane reduces the incidence and severity of early
      and late anthracycline cardiotoxicity in childhood solid tumors.

PMID- 20808680
TI  - Urodynamic and histological changes in a sterile rabbit vesicoureteral reflux
      model.
AB  - This study aimed to investigate pressure changes of renal pelvis and histological
      change of kidneys in a surgically induced sterile rabbit vesicoureteral reflux
      (VUR) model. Five rabbits served as a control group, 7 as the sham-operated
      group, and 8 served as the VUR group. Three weeks later, urodynamic studies were
      performed, and histological examinations evaluated degree of inflammation,
      fibrosis, and tubular damage in the kidneys. At a low infusion rate, renal pelvic
      pressure in the VUR group was stable until late filling phase and then increased
      slightly. At a high infusion rate, the renal pelvic pressures of the sham
      operated and control groups were stable until late filling phase and then
      increased slightly, whereas the renal pelvic pressure in the VUR group steadily
      increased from mid filling phase. Focal thinning of the tubular epithelium and
      interstitial widening were observed in certain cortical areas of refluxing
      kidneys, without inflammatory cell infiltration. Obvious changes in the mean
      diameters of distal tubules and extracellular matrix volume fractions were
      observed in two highly refluxing kidneys. High pressure reflux with bladder
      instability may result in renal cortical changes.

PMID- 20808679
TI  - Birth outcomes of Koreans by birthplace of infants and their mothers, the United
      States versus Korea, 1995-2004.
AB  - The acculturation effect of immigrant women on birth outcomes varies by race. We
      examined birth outcomes of three groups of births for the period 1995-2004, USA
      births to the USA-born Korean mothers, USA births to the non-USA-born Korean
      mothers, and births in Korea. In singleton USA births to both Korean parents,
      average birth weight was 3,294 g for the USA-born Korean mothers and 3,323 g for
      the non-USA-born Korean mothers. However, this difference was not significant,
      once controlled for other maternal sociodemographic, obstetric and medical
      factors. Low birth weight and prematurity prevalence were not different by
      maternal nativity between these two singleton groups. Average birth weight of all
      births including multiplets in Korea was 3,270 g, compared to 3,297 g for all USA
      born infants including multiplets and births either to both or one Korean
      parents. This difference might have reflected a significantly lower educational
      attainment of mothers in Korea compared to Korean mothers in the USA. Low birth
      weight rate was consistently lower in infants born in Korea compared to the USA
      born, but this difference became less, 4.2% and 4.6% respectively by 2004. These
      observations suggest that in the USA acculturation effect of Korean immigrants on
      birth outcomes is negligible.

PMID- 20808681
TI  - Motor unit number estimation in evaluating disease progression in patients with
      amyotrophic lateral sclerosis.
AB  - We investigated the availability of motor unit number estimation (MUNE) as a
      quantitative method to assess the severity and clinical progression of
      amyotrophic lateral sclerosis (ALS). The 143 ALS patients were evaluated by
      statistical MUNE and the revised amyotrophic lateral sclerosis functional rating
      scale (ALSFRS-R). By using mean values of MUNE according to disease duration,
      regression equation between mean MUNE and disease duration was presented as a
      formula. The individual MUNE ratio was calculated by dividing individual MUNE
      value by mean MUNE value. All patients were classified into 2 groups (MUNE ratio
      <1 vs. MUNE ratio >or=1) according to the MUNE ratio. Comparison between the 2
      groups revealed that the patients in MUNE ratio <1 group or MUNE ratio >or=1
      group were respectively assigned to rapid progression or slow progression. We
      recommended informative mean values of MUNE and best regression equation in ALS
      patients according to disease duration. These values allow us to evaluate the
      severity and rapidity of progression in ALS.

PMID- 20808682
TI  - A case of multicentric Castleman's disease having lung lesion successfully
      treated with humanized anti-interleukin-6 receptor antibody, tocilizumab.
AB  - This report presents the case of a patient demonstrating multicentric Castleman's
      disease (MCD) with a lung lesion that was successfully treated with an anti
      interleukin-6 receptor antibody, tocilizumab in combination with corticosteroid
      and tacrolimus. A 43-yr-old female with abnormal shadows on a chest X-ray was
      referred to the hospital for further examination. She was diagnosed as having MCD
      based on the characteristic pathology of inguinal lymph node, lung lesions,
      laboratory data, and undifferentiated arthritis. Corticosteroid and rituximab
      therapy did not fully ameliorate the symptoms; thus, the therapeutic regimen was
      changed to include tocilizumab, oral corticosteroid and tacrolimus. This regimen
      resulted in clinical remission and the dose of tocilizumab and corticosteroid
      could be tapered. Tocilizumab in combination with corticosteroid and tacrolimus
      may therefore be a beneficial treatment regimen for lung lesions associated with
      MCD.

PMID- 20808683
TI  - A case of resistance to thyroid hormone with thyroid cancer.
AB  - Resistance to thyroid hormone (RTH) is an autosomal dominant hereditary disorder
      that is difficult to diagnose because of its rarity and variable clinical
      features. The magnitude of RTH is caused by mutations in the thyroid hormone
      receptor beta (TR beta) gene. We recently treated a 38-yr-old woman with RTH who
      had incidental papillary thyroid carcinoma. She presented with goiter and
      displayed elevated thyroid hormone levels with an unsuppressed TSH. She was
      determined to harbor a missense mutation of M310T in exon 9 of the TR beta gene,
      and diagnosed with generalized RTH. This mutation has not yet been reported in
      Korea. RTH is very rare and easily overlooked, but should be considered in
      patients who present with goiter and elevated thyroid hormone levels with an
      unsuppressed TSH. The association between thyroid cancer and RTH needs further
      study.

PMID- 20808684
TI  - Acute kidney injury due to menstruation-related disseminated intravascular
      coagulation in an adenomyosis patient: a case report.
AB  - The authors report a case of acute kidney injury (AKI) resulting from
      menstruation-related disseminated intravascular coagulation (DIC) in an
      adenomyosis patient. A 40-yr-old woman who had received gonadotropin for
      ovulation induction therapy presented with anuria and an elevated serum
      creatinine level. Her medical history showed primary infertility with diffuse
      adenomyosis. On admission, her pregnancy test was negative and her menstrual
      cycle had started 1 day previously. Laboratory data were consistent with DIC, and
      it was believed to be related to myometrial injury resulting from heavy
      intramyometrial menstrual flow. Gonadotropin is considered to play an important
      role in the development of fulminant DIC. This rare case suggests that physicians
      should be aware that gonadotropin may provoke fulminant DIC in women with
      adenomyosis.

PMID- 20808685
TI  - Severe hypertriglyceridemia in diabetic ketoacidosis accompanied by acute
      pancreatitis: case report.
AB  - We report a case of diabetic ketoacidosis (DKA) and hypertriglyceridemia
      (severely elevated to 15,240 mg/dL) complicated by acute pancreatitis, which was
      treated successfully with insulin therapy and conservative management. A 20-yr
      old woman with a history of type 1 diabetes came to the emergency department 7
      months after discontinuing insulin therapy. DKA, severe hypertriglyceridemia and
      acute pancreatitis were diagnosed, with DKA suspected of contributing to the
      development of the other conditions. In Korea, two cases of DKA-induced
      hypertriglyceridemia and 13 cases of hypertriglyceridemia-induced acute
      pancreatitis have been previously reported separately.

PMID- 20808686
TI  - Genetic analyses of the chimeric CYP11B1/CYP11B2 gene in a Korean family with
      glucocorticoid-remediable aldosteronism.
AB  - Glucocorticoid-remediable aldosteronism (GRA) is an autosomal-dominant
      inheritable form of hyperaldosteronism with early onset hypertension. GRA is
      caused by unequal crossing-over of the steroid 11 beta-hydroxylase (CYP11B1) and
      aldosterone synthase (CYP11B2) genes. As a result of chimeric gene duplication,
      aldosterone is ectopically synthesized in the adrenal zona fasciculata under the
      control of adrenocorticotropin. Here, we describe three cases of GRA in a Korean
      family. The proband-a 21-yr-old female-was incidentally found to have high blood
      pressure (170/108 mmHg). Her 46-yr-old father had been treated twice for cerebral
      hemorrhage at the ages of 29 and 39 yr. Her 15-yr-old brother had a 2-yr history
      of hypertension; however, he was never treated. Their laboratory test results
      showed normokalemia, hyporeninemia, hyperaldosteronism, and a high plasma
      aldosterone concentration-to-plasma renin activity ratio. Normal saline loading
      failed to suppress aldosterone secretion. However, dexamethasone administration
      effectively suppressed their plasma aldosterone concentrations. Following genetic
      analyses with PCR and direct sequencing to document the chimeric gene and
      crossover site, respectively, we identified CYP11B1/CYP11B2 and determined the
      breakpoint of unequal crossover to be located between intron 2 of CYP11B1 and
      exon 3 of CYP11B2.

PMID- 20808687
TI  - Obstructive fibrinous tracheal pseudomembrane after tracheal intubation: a case
      report.
AB  - Obstructive fibrinous tracheal pseudomembrane is a rare, but potentially fatal
      complication associated with endotracheal intubation. It has been known that the
      formation of tracheal pseudomembrane is related with intracuff pressure during
      endotracheal intubation or infectious cause. But in the patient described in this
      case, pseudomembrane formation in the trachea was associated with subglottic
      epithelial trauma or caustic injuries to the trachea caused by aspirated gastric
      contents during intubation rather than tracheal ischemia due to high cuff
      pressure. We report a patient with obstructive fibrinous tracheal pseudomembrane
      after endotracheal intubation who presented with dyspnea and stridor and was
      treated successfully with mechanical removal using rigid bronchoscopy.

PMID- 20808688
TI  - The first Korean case of cutaneous lung tissue heterotopia.
AB  - Cutaneous lung tissue heterotopia is a very rare disorder where mature lung
      tissues develop in the skin. This is only the second known report of cutaneous
      lung tissue heterotopia, with the first by Singer et al. in 1998. A newborn
      infant had a hemangioma-like, freely movable mass connected to the anterior
      aspect of the sternal manubrium. Pathologic findings showed mature lung tissues
      with bronchi, bronchioles, and alveoli through the dermis and subcutis, and it
      was diagnosed as cutaneous lung tissue heterotopia. Cutaneous lung tissue
      heterotopia is hypervascular, so grossly it looks like a hemangioma. It can be
      differentiated from pulmonary sequestration, teratoma, bronchogenic cyst, and
      branchial cleft cyst by histology and the location of the mass. We describe the
      clinical, radiologic, and pathologic findings of a cutaneous lung tissue
      heterotopia, the first reported in Korea.

PMID- 20808690
TI  - A case of myxedema coma presenting as a brain stem infarct in a 74-year-old
      Korean woman.
AB  - Myxedema coma is the extreme form of untreated hypothyroidism. In reality, few
      patients present comatose with severe myxedema. We describe a patient with
      myxedema coma which was initially misdiagnosed as a brain stem infarct. She
      presented to the hospital with alteration of the mental status, generalized
      edema, hypothermia, hypoventilation, and hypotension. Initially her brain stem
      reflexes were absent. After respiratory and circulatory support, her neurologic
      status was not improved soon. The diagnosis of myxedema coma was often missed or
      delayed due to various clinical findings and concomitant medical condition and
      precipitating factors. It is more difficult to diagnose when a patient has no
      medical history of hypothyroidism. A high index of clinical suspicion can make a
      timely diagnosis and initiate appropriate treatment. We report this case to alert
      clinicians considering diagnosis of myxedema coma in patients with severe
      decompensated metabolic state including mental change.

PMID- 20808689
TI  - Warfarin-induced penile necrosis in a patient with heparin-induced
      thrombocytopenia.
AB  - A 56-yr-old man with lung adenocarcinoma presented with subsegmental pulmonary
      thrombosis. Platelet count on presentation was 531 x 10(9)/L. The patient was
      anticoagulated with subcutaneous low molecular weight heparin (LMWH). Next day,
      oral anticoagulation was initiated with 5 mg of warfarin once daily with LMWH and
      LMWH was discontinued at third hospital day. On the third day of oral
      anticoagulation therapy, he complained of left leg swelling and prolonged painful
      penile erection of 24 hr-duration. His platelet count reached a nadir 164 x
      10(9)/L at that time, and the patient had a deficiency of protein C and S, with
      an activity level of 16% and 20% of normal value. Warfarin was stopped and he
      underwent penile aspiration. The next day, left leg edema and penile erection was
      disappeared, but penile and glans penis necrosis was started. This case
      illustrates that processes underlying heparin-induced thrombocytopenia (HIT) may
      also underlie warfarin-induced skin necrosis.

PMID- 20808691
TI  - Two cases of transfusion-related acute lung injury triggered by HLA and anti-HLA
      antibody reaction.
AB  - Transfusion-related acute lung injury (TRALI) is a serious adverse transfusion
      reaction that is presented as acute hypoxemia and non-cardiogenic pulmonary
      edema, which develops during or within 6 hr of transfusion. Major pathogenesis of
      TRALI is known to be related with anti-HLA class I, anti-HLA class II, or anti
      HNA in donor's plasma. However, anti-HLA or anti-HNA in recipient against
      transfused donor's leukocyte antigens also cause TRALI in minor pathogenesis and
      which comprises about 10% of TRALI. Published reports of TRALI are relatively
      rare in Korea. In our cases, both patients presented with dyspnea and hypoxemia
      during transfusion of packed red blood cells and showed findings of bilateral
      pulmonary infiltrations at chest radiography. Findings of patients' anti-HLA
      antibodies and recipients' HLA concordance indicate that minor pathogenesis may
      be not as infrequent as we'd expected before. In addition, second case showed
      that anti-HLA class II antibodies could be responsible for immunopathogenic
      mechanisms, alone.

PMID- 20808692
TI  - Benign strictures of the esophagus and gastric outlet: interventional management.
AB  - Benign strictures of the esophagus and gastric outlet are difficult to manage
      conservatively and they usually require intervention to relieve dysphagia or to
      treat the stricture-related complications. In this article, authors review the
      non-surgical options that are used to treat benign strictures of the esophagus
      and gastric outlet, including balloon dilation, temporary stent placement,
      intralesional steroid injection and incisional therapy.

PMID- 20808693
TI  - Functional neuroanatomy associated with natural and urban scenic views in the
      human brain: 3.0T functional MR imaging.
AB  - OBJECTIVE: By using a functional magnetic resonance imaging (fMRI) technique we
      assessed brain activation patterns while subjects were viewing the living
      environments representing natural and urban scenery. MATERIALS AND METHODS: A
      total of 28 healthy right-handed subjects underwent an fMRI on a 3.0 Tesla MRI
      scanner. The stimulation paradigm consisted of three times the rest condition and
      two times the activation condition, each of which lasted for 30 and 120 seconds,
      respectively. During the activation period, each subject viewed natural and urban
      scenery, respectively. RESULTS: The predominant brain activation areas observed
      following exposure to natural scenic views in contrast with urban views included
      the superior and middle frontal gyri, superior parietal gyrus, precuneus, basal
      ganglia, superior occipital gyrus, anterior cingulate gyrus, superior temporal
      gyrus, and insula. On the other hand, the predominant brain activation areas
      following exposure to urban scenic views in contrast with natural scenes included
      the middle and inferior occipital gyri, parahippocampal gyrus, hippocampus,
      amygdala, anterior temporal pole, and inferior frontal gyrus. CONCLUSION: Our
      findings support the idea that the differential functional neuroanatomies for
      each scenic view are presumably related with subjects' emotional responses to the
      natural and urban environment, and thus the differential functional neuroanatomy
      can be utilized as a neural index for the evaluation of friendliness in
      ecological housing.

PMID- 20808694
TI  - Myocardial bridging of the left anterior descending coronary artery: depiction
      rate and morphologic features by dual-source CT coronary angiography.
AB  - OBJECTIVE: To evaluate the depiction rate and morphologic features of myocardial
      bridging (MB) of the left anterior descending coronary artery (LAD) using dual
      source CT (DSCT). MATERIALS AND METHODS: CT scans from a total of 1,353 patients
      who underwent DSCT were reviewed retrospectively for LAD-MB. Seventy-eight
      patients were excluded due to poor image quality or poor enhancement of the
      coronary artery. The length and depth of the MB were analyzed and classified as
      superficial or deep with respect to the depth (<or= 1 or > 1 mm) of the LAD
      tunneled segment. Superficial MB was subdivided into complete or incomplete types
      according to full or partial encasement of the myocardium. RESULTS: Of the 1,275
      patients included in this study, 557 cases of MB were found from 536 patients
      (42%). Superficial MB was observed in 368 of 557 (66%) cases, and deep MB was
      seen in 189 of 557 (34%) cases. Superficial MB showed 2 types: complete (128 of
      368, 35%) and incomplete (240 of 368, 65%). The mean length of a tunneled segment
      for superficial MB was 16.4 +/- 8.6 mm. The mean length and depth of a tunneled
      segment for deep MB were 27.6 +/- 12.8 mm and 3.0 +/- 1.4 mm, respectively. The
      incidence of atherosclerotic plaques in a 2-cm-long segment proximal to MB was
      16%. CONCLUSION: The depiction rate of LAD-MB using DSCT in a large series of
      patients was 42%, with two-thirds of MB segments being the superficial type.

PMID- 20808695
TI  - Ultrasonographic features of benign adenomyoepithelioma of the breast.
AB  - OBJECTIVE: The purpose of this study was to evaluate the ultrasonographic
      features of benign adenomyoepithelioma of the breast. MATERIALS AND METHODS:
      Between 2005 and 2009, five patients had histologically confirmed
      adenomyoepithelioma of the breast. We retrospectively evaluated the
      ultrasonographic findings of the tumors in correlation with the pathology, and
      reviewed medical records. RESULTS: The clinical manifestations included a
      palpable mass in three patients, while mammographic screening helped detect
      abnormalities in two patients. Ultrasonograms showed masses with an oval (n = 3)
      or irregular (n = 2) shape, with uncircumscribed (n = 4) or relatively well
      circumscribed (n = 1) margins, as well as with a hypoechoic (n = 3) or a complex
      echoic (n = 2) internal echo texture. Three patients had focal ductectasia
      adjacent to the mass. The ultrasonographic assessments were classified as Breast
      Imaging Reporting and Data System (BI-RADS) category 4A, with low suspicion of
      malignancy in two cases, and as category 4B, with intermediate suspicion of
      malignancy in three cases. The pathology revealed benign adenomyoepithelioma in
      all patients. CONCLUSION: Benign adenomyoepitheliomas appear as solid or complex
      echoic masses with suspicious malignant ultrasonographic features, which may be
      associated with adjacent ductectasia. Although adenomyoepithelioma is a rare
      breast tumor, awareness of its sonographic features will be helpful for the
      differential diagnosis from other tumors.

PMID- 20808696
TI  - Comparisons of the various partial-thickness rotator cuff tears on MR
      arthrography and arthroscopic correlation.
AB  - OBJECTIVE: To assess the diagnostic performance of MR arthrography in the
      diagnosis of the various types of partial-thickness rotator cuff tears by
      comparing the MR imaging findings with the arthroscopic findings. MATERIALS AND
      METHODS: The series of MR arthrography studies included 202 patients consisting
      of 100 patients with partial-thickness rotator cuff tears proved by arthroscopy
      and a control group of 102 patients with arthroscopically intact rotator cuffs,
      which were reviewed in random order. At arthroscopy, 54 articular-sided, 26
      bursal-sided, 20 both articular- and bursal-sided partial-thickness tears were
      diagnosed. The MR arthrographies were analyzed by two radiologists for articular
      sided tears, bursal-sided tears, and both articular- and bursal-sided tears of
      the rotator cuff. The sensitivity and specificity of each type of partial
      thickness tears were determined. Kappa statistics was calculated to determine the
      inter- and intra-observer agreement of the diagnosis of partial-thickness rotator
      cuff tears. RESULTS: The sensitivity and specificity of the various types of
      rotator cuff tears were 85% and 90%, respectively for articular-sided tears, 62%
      and 95% for bursal-sided tears, as well as 45% and 99% for both articular- and
      bursal-sided tears. False-negative assessments were primarily observed in the
      diagnosis of bursal-sided tears. Conversely, both articular- and bursal-sided
      tears were overestimated as full-thickness tears. Inter-observer agreement was
      excellent for the diagnosis of articular-sided tears (k = 0.70), moderate (k =
      0.59) for bursal-sided tears, and fair (k = 0.34) for both articular- and bursal
      sided tears, respectively. Intra-observer agreement for the interpretation of
      articular- and bursal-sided tears was excellent and good, respectively, whereas
      intra-observer agreement for both articular- and bursal-sided tears was moderate.
      CONCLUSION: MR arthrography is a useful diagnostic tool for partial-thickness
      rotator cuff tears, but has limitations in that it has low sensitivity in bursal-
      and both articular- and bursal-sided tears. In addition, it shows only fair inter
      observer agreement when it comes to predicting both articular- and bursal-sided
      tears.

PMID- 20808697
TI  - Endovascular coil embolization of very small intracranial aneurysms.
AB  - OBJECTIVE: We aimed to evaluate the results of endovascular coil embolization for
      very small aneurysms (<or= 3 mm). MATERIALS AND METHODS: Between March 2005 and
      December 2008, a total of 31 very small aneurysms in 30 patients were treated by
      coil embolization. Of the 31 aneurysms, five (16%) were ruptured, as opposed to
      26 (84%) that were not. We assessed the procedural complications, immediate
      angiographic outcome after coiling, clinical outcome, and follow-up MR
      angiography (MRA). RESULTS: Two thromboembolic complications occurred during the
      procedure, but did not lead to any persistent neurologic deficit. No procedural
      aneurysmal rupture was observed and procedure-related morbidity and mortality
      were both 0%. Occlusion was adequate in 25 aneurysms (81%) and incomplete in six
      aneurysms (19%). The clinical outcomes of five patients with ruptured aneurysms
      were good (Glasgow outcome scale >or= 4), with no bleeding of the treated
      aneurysms during a mean follow-up period of 13.3 months. On 27 follow-up MRA,
      there was no recurrence, and the five incompletely occluded aneurysms showed a
      spontaneous amelioration resulting in an adequate occlusion. CONCLUSION: Coil
      embolization of very small aneurysms is technically feasible with good results.
      The long-term efficacy and the potential as a standard treatment strategy remain
      to be determined by randomized large trials.

PMID- 20808698
TI  - Comparison of the effectiveness of embolic agents for bronchial artery
      embolization: gelfoam versus polyvinyl alcohol.
AB  - OBJECTIVE: The purpose of this study was to compare the results of different
      agents for bronchial artery embolization of hemoptysis. MATERIALS AND METHODS:
      From March 1992 to December 2006, a bronchial artery embolization was performed
      on 430 patients with hemoptysis. The patients were divided into three groups.
      Group 1 included 74 patients treated with a gelfoam particle (1 x 1 x 1 mm),
      while group 2 comprised of 205 patients treated with polyvinyl alcohol (PVA) at
      355-500 microm, and group 3 included 151 patients treated with PVA at 500-710
      microm. We categorized the results as technical and clinical successes, and also
      included the mid-term results. Retrospectively, the technical success was
      compared immediately after the procedure. The clinical success and mid-term
      results (percentage of patients who were free of hemoptysis) were compared at 1
      and 12 months after the procedure, respectively. RESULTS: Neither the technical
      successes (group 1; 85%, 2; 85%, 3; 90%) nor the clinical successes (group 1;
      72%, 2; 74%, 3; 71%) showed a significant difference among the 3 groups (p >
      0.05). However, the mid-term results (group 1; 45%, 2; 63%, 3; 62%) and mid-term
      results excluding the recurrence from collateral vessels in each of the groups
      (group 1; 1 patient, 2; 4 patients, 3; 2 patients) showed that group 1 was lower
      than the other two groups (p < 0.05). No significant difference was discovered
      for the mid-term results between groups 2 and 3. Moreover, the same results not
      including incidences of recurrence from collateral vessels also showed no
      statistical significance between the two groups (p > 0.05). CONCLUSION: Polyvinyl
      alcohol appears to be the more optimal modality compared to gelfoam particle for
      bronchial artery embolization in order to improve the mid-term results. The
      material size of PVA needs to be selected to match with the vascular diameter.

PMID- 20808700
TI  - Image quality improvement after implementation of a CT accreditation program.
AB  - OBJECTIVE: The purpose of this study was to evaluate any improvement in the
      quality of abdominal CTs after the utilization of the nationally based
      accreditation program. MATERIALS AND METHODS: Approval was obtained from the
      Institutional Review Board, and informed consent was waived. We retrospectively
      analyzed 1,011 outside abdominal CTs, from 2003 to 2007. We evaluated images
      using a fill-up sheet form of the national accreditation program, and
      subjectively by grading for the overall CT image quality. CT scans were divided
      into two categories according to time periods; before and after the
      implementation of the accreditation program. We compared CT scans between two
      periods according to parameters pertaining to the evaluation of images. We
      determined whether there was a correlation between the results of a subjective
      assessment of the image quality and the evaluation scores of the clinical image.
      RESULTS: The following parameters were significantly different after the
      implementation of the accreditation program: identifying data, display
      parameters, scan length, spatial and contrast resolution, window width and level,
      optimal contrast enhancement, slice thickness, and total score. The remaining
      parameters were not significantly different between scans obtained from the two
      different periods: scan parameters, film quality, and artifacts. CONCLUSION:
      After performing the CT accreditation program, the quality of the outside
      abdominal CTs show marked improvement, especially for the parameters related to
      the scanning protocol.

PMID- 20808699
TI  - Estimation of radiation exposure of 128-slice 4D-perfusion CT for the assessment
      of tumor vascularity.
AB  - OBJECTIVE: We aimed to estimate the effective dose of 4D-Perfusion-CT protocols
      of the lung, liver, and pelvis for the assessment of tumor vascularity. MATERIALS
      AND METHODS: An Alderson-Rando phantom equipped with thermoluminescent dosimeters
      was used to determine the effective dose values of 4D-Perfusion-CT. Phantom
      measurements were performed on a 128-slice single-source scanner in adaptive 4D
      spiral-mode with bidirectional table movement and a total scan range of 69 mm
      over a time period of nearly 120 seconds (26 scans). Perfusion measurements were
      simulated for the lung, liver, and pelvis under the following conditions: lung
      (80 kV, 60 mAs), liver (80 kV/80 mAs and 80 kV/120 mAs), pelvis (100 kV/80 mAs
      and 100 kV/120 mAs). RESULTS: Depending on gender, the evaluated body region and
      scan protocol, an effective whole-body dose between 2.9-12.2 mSv, was determined.
      The radiation exposure administered to gender-specific organs like the female
      breast tissue (lung perfusion) or to the ovaries (pelvic perfusion) led to an
      increase in the female specific dose by 86% and 100% in perfusion scans of the
      lung and the pelvis, respectively. CONCLUSION: Due to a significant radiation
      dose of 4D-perfusion-CT protocols, the responsible use of this new promising
      technique is mandatory. Gender- and organ-specific differences should be
      considered for indication and planning of tumor perfusion scans.

PMID- 20808701
TI  - Imaging findings of intrahepatic bile duct adenoma (peribiliary gland hamartoma):
      a case report and literature review.
AB  - Intrahepatic bile duct adenoma is a rare benign epithelial hepatic tumor derived
      from bile duct cells. We report the imaging findings of a patient with bile duct
      adenoma, which appeared as a small heterogeneously enhancing mass with focal
      small cystic change on CT and MRI. Follow-up images at seven months showed a
      slight increase in tumor size, which could be partly explained by intratumoral
      hemorrhage on pathologic examination. Although rare, bile duct adenoma should be
      considered as a differential diagnosis of a small hypervascular tumor located in
      the periphery of liver. Focal cystic change and intratumoral hemorrhage may
      occur.

PMID- 20808702
TI  - Gliosarcoma of the cerebellar hemisphere: a case report and review of the
      literature.
AB  - Gliosarcoma is a rare central nervous system tumor usually located in the
      supratentorial area. Here we report a rare case of a gliosarcoma that developed
      in the cerebellar hemisphere in a 70-year-old woman. Computed tomography (CT) and
      magnetic resonance imaging (MRI) of the brain revealed an infratentorial mass of
      which radiological features were similar to those of glioblastoma. The tumor was
      diagnosed by pathology as a gliosarcoma. Though rare, gliosarcoma should be
      considered in the differential diagnosis of infratentorial tumors with
      radiological features of glioblastoma or metastasis in elderly patients.

PMID- 20808703
TI  - Linear fat deposition in the middle layer of the left ventricular myocardium:
      computed tomographic findings.
AB  - We report here a case of streaky fat deposition in the middle layer of the left
      ventricular myocardium, without any underlying etiology, and this was seen on
      computed tomography coronary angiography. This report suggests that left
      ventricular middle layer fat deposition should be investigated in order to
      determine its etiology, the pathogenesis and the prognosis.

PMID- 20808704
TI  - Transcatheter arterial embolization using ethanol in a dialysis patient for
      contracting enlarged polycystic kidneys.
AB  - The mass effect of nephromegaly in patients with autosomal dominant polycystic
      kidney disease may cause pain and symptoms by compressing the alimentary tract,
      lungs, and heart. Conventional therapies exist to contract enlarged polycystic
      kidneys including surgical and interventional procedures. A surgical nephrectomy
      is often difficult to perform in dialysis patients due to the associated risks
      related to surgery. In contrast, renal transcatheter arterial embolization (TAE)
      with metallic coils, which is a less invasive interventional procedure, can also
      be utilized to contract enlarged kidneys in dialysis patients as an effective
      treatment. However, metallic coils present the possibility of recanalization and
      cost issues. Thus, we used ethanol instead of coils in renal TAE to resolve these
      issues. We report a dialysis patient with enlarged polycystic kidneys and poor
      oral intake due to abdominal distention that was successfully treated by TAE with
      absolute ethanol.

PMID- 20808705
TI  - Papillary thyroid carcinoma of a diffuse sclerosing variant: ultrasonographic
      monitoring from a normal thyroid gland to mass formation.
AB  - A diffuse sclerosing variant of papillary thyroid carcinoma is uncommon and has a
      tendency for rapid growth and a higher incidence of cervical lymph node
      metastases. We experienced a case of a diffuse sclerosing variant of papillary
      thyroid carcinoma in a 48-year-old man. This case showed benign features on
      initial ultrasonography and positron emission tomography (PET) scan. A new nodule
      was detected on follow-up ultrasonography that showed rapid enlargement. This
      case was confirmed by surgical excision. We herein describe the initial and
      follow-up ultrasonographic findings of a diffuse sclerosing variant of papillary
      thyroid carcinoma.

PMID- 20808706
TI  - Congenital intrahepatic portosystemic venous shunt and liver mass in a child
      patient: successful endovascular treatment with an amplatzer vascular plug (AVP).
AB  - A congenital intrahepatic portosystemic shunt is a rare anomaly; but, the number
      of diagnosed cases has increased with advanced imaging tools. Symptomatic
      portosystemic shunts, especially those that include hyperammonemia, should be
      treated; and various endovascular treatment methods other than surgery have been
      reported. Hepatic masses with either an intra- or extrahepatic shunt also have
      been reported, and the mass is another reason for treatment. Authors report a
      case of a congenital intrahepatic portosystemic shunt with a hepatic mass that
      was successfully treated using a percutaneous endovascular approach with vascular
      plugs. By the time the first short-term follow-up was conducted, the hepatic mass
      had disappeared.

PMID- 20808707
TI  - Follow-up aspects of influenza A (H1N1) virus-associated pneumonia: the role of
      high-resolution computed tomography in the evaluation of the recovery phase.

PMID- 20808709
TI  - Design of an electron microscope phase plate using a focused continuous-wave
      laser.
AB  - We propose a Zernike phase contrast electron microscope that uses an intense
      laser focus to convert a phase image into a visible image. We present the
      relativistic quantum theory of the phase shift caused by the laser-electron
      interaction, study resonant cavities for enhancing the laser intensity and
      discuss applications in biology, soft-materials science and atomic and molecular
      physics.

PMID- 20808710
TI  - Same-sex Versus Other-sex Best Friendship in Early Adolescence: Longitudinal
      Predictors of Antisocial Behavior Throughout Adolescence.
AB  - This study examines the relationship between having other-sex versus same-sex
      best friends and antisocial behavior throughout early adolescence. Participants
      (N = 955) were recruited in 6th grade and followed longitudinally through 7th,
      8th, and 11th grades. Participants were 58% ethnically diverse youth and 48%
      girls. Results indicate that the frequency of other-sex best friendship remained
      stable from 6th to 7th grade but significantly increased from 8th to 11th grade.
      Higher rates of concurrent antisocial behavior were related to having other-sex
      best friends in 6th grade but not in 7th grade. In 8th grade, there was an
      interaction between friendship and the sex of friends. Boys with only same-sex
      best friends and girls with other-sex best friends endorsed higher rates of
      antisocial behavior. Having other-sex best friends predicted antisocial behavior
      from 6th to 7th grade and 8th to 11th grade, especially for girls. Implications
      for the development of early adolescent friendship and antisocial behavior are
      discussed.

PMID- 20808711
TI  - Kyol Goeu ('Wind Overload') Part II: Prevalence, Characteristics, and Mechanisms
      of Kyol Goeu and Near-Kyol Goeu Episodes of Khmer Patients Attending a
      Psychiatric Clinic.
AB  - Kyol goeu (literally, 'wind overload') is an orthostatically triggered syncopal
      syndrome often found among Khmer refugees in the US. In the present study, 36 of
      100 (36%) Khmer patients attending a psychiatric clinic were found to have
      suffered a kyol goeu episode in the past, whereas 60 of 100 (60%) patients had
      experienced a near-kyol goeu event in the last six months. Following a survey
      based characterization of kyol goeu, as well as the presentation of case
      vignettes, the article discusses six mechanisms resulting in the high prevalence
      of the syndrome. The article concludes by comparing kyol goeu and ataque de
      nervios.

PMID- 20808712
TI  - HIV TAT Protein Transduction Domain Mediated Cell Binding and Intracellular
      Delivery of Nanoparticles.
AB  - Intracellular delivery of non-transported therapeutic agents has traditionally
      been thought possible only for low molecular weight (<500 DA) hydrophobic
      molecules. Higher molecular weight agents including oligonucleotides, proteins,
      DNA, liposomes, and nanoparticles do not readily enter the cytoplasm. However,
      the human immunodeficiency virus (HIV) trans-acting transcriptional activator
      (TAT) protein enters the cytosol by way of an 11 amino acid cationic peptide
      (TATp). When this cationic sequence is attached to a variety of small
      pharmacological agents, including paramagnetic ions[1,2] and proteins,[3-6] they
      are delivered into cells. Further, TATp modification of large cargo, such as
      proteins, polymers, and nanoparticles, may enable them to internalize into cells
      as well. The size limitations for cargo delivered by a single TATp are currently
      undetermined, but multiple TATp attached to polymers, nanoparticles, liposomes,
      and phage can definitely mediate their internalization. This process appears to
      follow an endocytotic or potocytic pathway and does not directly transfer the
      cargo into the cytoplasm of the cell. Here we review recent publications in which
      multiple TATp have been attached to and resulted in the successful intracellular
      delivery of nanoparticles.

PMID- 20808713
TI  - Fluorescence Investigations into Complex Coacervation between Polyvinylimidazole
      and Sodium Alginate.
AB  - Electrostatic interactions between the imidazole-based cationic homopolymer,
      polyvinylimidazole (PVIm), and anionic polysaccharide, sodium alginate, lead to
      the formation of colloidal aggregates known as complex coacervates in the pH
      range 4-6.5. PVIm was labeled with the fluorescent reporter pyrene to investigate
      the coacervation-induced changes in and around PVIm chains. While the pyrene
      tagged PVIm had blue fluorescence in water, the coacervate phase exhibited an
      additional broad band around 492 nm (green) due to formation of pyrene excimers.
      Fluorescence spectroscopic investigations point toward aggregation of PVIm chains
      and desolvation upon coacervation. Highly anisotropic fluorescence emission
      indicates tight packing of the polymer chains in the coacervate. Confocal
      microscopy of fluorescein-labeled alginate and rhodamine-labeled PVIm shows
      coacervates as dense aggregates with uniform distribution of the polymers.
      Fluorescence spectroscopy offers sensitive and easy investigation into
      polyelectrolyte interactions.

PMID- 20808714
TI  - Detecting Adverse Drug Events Using a Nursing Home Specific Trigger Tool.

PMID- 20808715
TI  - A MedlinePlus Kiosk Promoting Health Literacy.
AB  - As an ongoing community outreach project, a pictorial touch-screen kiosk and Web
      site was developed for 48 MedlinePlus((R)) tutorials. This learning experience
      serves Davidson County, Tennessee's uninsured patients at the University of
      Tennessee/Baptist Hospital's Internal Medicine Clinic. The availability of a
      health information kiosk at the University of Tennessee/Baptist Hospital primary
      care clinic significantly increases health literacy for patients by providing
      reliable, physician-recommended information in an appropriate format-information
      these patients did not previously find readily available. Participants report
      they have a greater understanding of their health issues, and the project is
      introducing hundreds of patients to MedlinePlus.

PMID- 20808716
TI  - Binding of Two Different DNA Sequences by Conformational Switching.

PMID- 20808717
TI  - Strong, Specific Binding of Six Different DNA Sequences by a Single Conformation
      Switching DNA Macrocycle.

PMID- 20808718
TI  - Dynamics of multicomponent vesicles in a viscous fluid.
AB  - We develop and investigate numerically a thermodynamically consistent model of
      two-dimensional multicomponent vesicles in an incompressible viscous fluid. The
      model is derived using an energy variation approach that accounts for different
      lipid surface phases, the excess energy (line energy) associated with surface
      phase domain boundaries, bending energy, spontaneous curvature, local
      inextensibility and fluid flow via the Stokes equations. The equations are high
      order (fourth order) nonlinear and nonlocal due to incompressibil-ity of the
      fluid and the local inextensibility of the vesicle membrane. To solve the
      equations numerically, we develop a nonstiff, pseudo-spectral boundary integral
      method that relies on an analysis of the equations at small scales. The algorithm
      is closely related to that developed very recently by Veerapaneni et al. [81] for
      homogeneous vesicles although we use a different and more efficient time stepping
      algorithm and a reformulation of the inextensibility equation. We present
      simulations of multicomponent vesicles in an initially quiescent fluid and
      investigate the effect of varying the average surface concentration of an
      initially unstable mixture of lipid phases. The phases then redistribute and
      alter the morphology of the vesicle and its dynamics. When an applied shear is
      introduced, an initially elliptical vesicle tank-treads and attains a steady
      shape and surface phase distribution. A sufficiently elongated vesicle tumbles
      and the presence of different surface phases with different bending stiffnesses
      and spontaneous curvatures yields a complex evolution of the vesicle morphology
      as the vesicle bends in regions where the bending stiffness and spontaneous
      curvature are small.

PMID- 20808720
TI  - Contrasting Models of Posttraumatic Stress Disorder: Reply to.
AB  - We address the four main points in Monroe and Mineka (2008)'s Comment. First, we
      first show that the DSM PTSD diagnosis includes an etiology and that it is based
      on a theoretical model with a distinguished history in psychology and psychiatry.
      Two tenets of this theoretical model are that voluntary (strategic) recollections
      of the trauma are fragmented and incomplete while involuntary (spontaneous)
      recollections are vivid and persistent and yield privileged access to traumatic
      material. Second, we describe differences between our model and other cognitive
      models of PTSD. We argue that these other models share the same two tenets as the
      diagnosis and we show that these two tenets are largely unsupported by empirical
      evidence. Third, we counter arguments about the strength of the evidence favoring
      the mnemonic model, and fourth, we show that concerns about the causal role of
      memory in PTSD are based on views of causality that are generally inappropriate
      for the explanation of PTSD in the social and biological sciences.

PMID- 20808722
TI  - An Artificial Multi-Channel Model for Generating Abnormal Electrocardiographic
      Rhythms.
AB  - We present generalizations of our previously published artificial models for
      generating multi-channel ECG so that the simulation of abnormal rhythms is
      possible. Using a three-dimensional vectorcardiogram (VCG) formulation, we
      generate the normal cardiac dipole for a patient using a sum of Gaussian kernels,
      fitted to real VCG recordings. Abnormal beats are then specified either as new
      dipoles, or as perturbations of the existing dipole. Switching between normal and
      abnormal beat types is achieved using a hidden Markov model (HMM). Probability
      transitions can be learned from real data or modeled by coupling to heart rate
      and sympathovagal balance. Natural morphology changes form beat-to-beat are
      incorporated as before from varying the angular frequency of the dipole as a
      function of the inter-beat (RR) interval. The RR interval time series is
      generated using our previously described model whereby time-and frequency-domain
      heart rate (HR) and heart rate variability (HRV) characteristics can be
      specified. QT-HR hysteresis is simulated by coupling the Gaussian kernels
      associated with the T-wave in the model with a nonlinear factor related to the
      local HR (determined from the last n RR intervals). Morphology changes due to
      respiration are simulated by coupling the RR interval to the angular frequency of
      the dipole. We demonstrate an example of the use of this model by simulating T
      Wave Alternans (TWA). The magnitude of the TWA effect is modeled as a disturbance
      on the T-loop of the dipole with a magnitude that differs in each of the three
      VCG planes. The effect is then turned on or off using a HMM. The values of the
      transition matrix are determined by the local heart rate, such that when the HR
      ramps up towards 100 BPM, the probability of observing a TWA effect rapidly but
      smoothly increases. In this way, no 'sudden' switching from non-TWA to TWA is
      observed, and the natural tendency for TWA to be associated with a critical HR
      related activation level is simulated. Finally, to generate multi-lead signals,
      the VCG is mapped to any set of clinical leads using a Dower-like transform
      derived from a least-squares optimization between known VCGs and known lead
      morphologies. ECGs with calibrated amounts of TWA were generated by this model
      and included in the PhysioNet/CinC Challenge 2008 data set.

PMID- 20808721
TI  - Challenges for Molecular Neuroimaging with MRI.
AB  - Magnetic resonance (MRI)-based molecular imaging methods are beginning to have
      impact in neuroscience. A growing number of molecular imaging agents have been
      synthesized and tested in vitro, but so far relatively few have been validated in
      the brains of live animals. Here, we discuss key challenges associated with
      expanding the repertoire of successful molecular neuroimaging approaches. The
      difficulty of delivering agents past the blood-brain barrier (BBB) is a
      particular obstacle to molecular imaging in the central nervous system. We review
      established and emerging techniques for trans-BBB delivery, including
      intracranial infusion, BBB disruption, and transporter-related methods. Improving
      the sensitivity with which MRI-based molecular agents can be detected is a second
      major challenge. Better sensitivity would in turn reduce the requirements for
      delivery and alleviate potential side effects. We discuss recent efforts to
      enhance relaxivity of conventional longitudinal relaxation time (T(1)) and
      transverse relaxation time (T(2)) MRI contrast agents, as well as strategies that
      involve amplifying molecular signals or reducing endogenous background
      influences. With ongoing refinement of imaging approaches and brain delivery
      methods, MRI-based techniques for molecular-level neuroscientific investigation
      will fall increasingly within reach.

PMID- 20808723
TI  - Denitrification capabilities of two biological phosphorus removal sludges
      dominated by different "Candidatus Accumulibacter" clades.
AB  - The capability of "Candidatus Accumulibacter" to use nitrate as an electron
      acceptor for phosphorus uptake was investigated using two activated sludge
      communities. The two communities were enriched in Accumulibacter clade IA and
      clade IIA, respectively. By performing a series of batch experiments, we found
      that clade IA was able to couple nitrate reduction with phosphorus uptake, but
      clade IIA could not. These results agree with a previously proposed hypothesis
      that different populations of Accumulibacter have different nitrate reduction
      capabilities, and they will help to understand the ecological roles that these
      two clades provide.

PMID- 20808725
TI  - Cobaltacarborane-phthalocyanine conjugates: Syntheses and photophysical
      properties.
AB  - Syntheses of two new cobaltacarborane-phthalocyanine conjugates, one anionic (Pc
      6) and one zwitterionic (Pc 7), were accomplished via cyclotetramerization of the
      corresponding cobaltacarborane-substituted phthalonitriles (4 or 5) with excess
      phthalonitrile in quinoline. X-ray structures of two phthalonitrile precursors (2
      and 3) were obtained and are discussed, and the absorption and emission
      properties of the two cobaltacarborane-phthalocyanine conjugates in several
      solvents were investigated. The anionic conjugate 6 exists mainly as a monomer in
      polar organic solvents and has fluorescence quantum yields in the region 0.2-0.3.
      The zwitterionic conjugate 7 aggregates in solution and displays lower quantum
      yields ~0.1 in organic solvents.

PMID- 20808724
TI  - Role of Chemokines and Chemokine Receptors in Prostate Cancer Development and
      Progression.
AB  - Prostate cancer (PC) is the second leading cause of cancer deaths in men in
      America and Western Europe. Epidemiological studies suggest that prostate cancer
      incidences increased in last few years in Asian. The causes or consequences of
      increasing trend of prostate cancer incidence are not completely known. Emerging
      evidences suggest that among the many risk factors, inflammation is the major
      risk factor for developing prostate cancer and its progression to metastasis. It
      is proposed that exposure to environmental factors such as infectious agents,
      dietary agents and saturated lipids leads to injury of the prostate due to
      chronic inflammation and regenerative risk factor lesions referred to as
      proliferative inflammatory atrophy (PIA). These phenomena predominantly control
      by a number of proinflammatory macro molecules such as chemokines, and their
      receptors. Some recent studies suggest that many of these pro-inflammatory
      chemokines and their receptors are the products of protooncogenes in many cancers
      including that of the prostate. This review will focus on the current biology of
      chemokines and chemokine receptors in prostate cancer. An understanding of this
      axis may enable researchers to develop targeted strategies for prostate cancer.

PMID- 20808719
TI  - Nonlinear modelling of cancer: bridging the gap between cells and tumours.
AB  - Despite major scientific, medical and technological advances over the last few
      decades, a cure for cancer remains elusive. The disease initiation is complex,
      and including initiation and avascular growth, onset of hypoxia and acidosis due
      to accumulation of cells beyond normal physiological conditions, inducement of
      angiogenesis from the surrounding vasculature, tumour vascularization and further
      growth, and invasion of surrounding tissue and metastasis. Although the focus
      historically has been to study these events through experimental and clinical
      observations, mathematical modelling and simulation that enable analysis at
      multiple time and spatial scales have also complemented these efforts. Here, we
      provide an overview of this multiscale modelling focusing on the growth phase of
      tumours and bypassing the initial stage of tumourigenesis. While we briefly
      review discrete modelling, our focus is on the continuum approach. We limit the
      scope further by considering models of tumour progression that do not distinguish
      tumour cells by their age. We also do not consider immune system interactions nor
      do we describe models of therapy. We do discuss hybrid-modelling frameworks,
      where the tumour tissue is modelled using both discrete (cell-scale) and
      continuum (tumour-scale) elements, thus connecting the micrometre to the
      centimetre tumour scale. We review recent examples that incorporate experimental
      data into model parameters. We show that recent mathematical modelling predicts
      that transport limitations of cell nutrients, oxygen and growth factors may
      result in cell death that leads to morphological instability, providing a
      mechanism for invasion via tumour fingering and fragmentation. These conditions
      induce selection pressure for cell survivability, and may lead to additional
      genetic mutations. Mathematical modelling further shows that parameters that
      control the tumour mass shape also control its ability to invade. Thus, tumour
      morphology may serve as a predictor of invasiveness and treatment prognosis.

PMID- 20808726
TI  - Migration in the Americas: Mexico and Latin America in Comparative Context.

PMID- 20808727
TI  - Expectations and Realization of Joint Retirement among Dual-Worker Couples.
AB  - Using data from the first seven waves of the Health and Retirement Study (1992 to
      2004), the authors examined the extent to which joint retirement expectations
      were realized, the role of couple-level agreement in facilitating joint
      retirement, whether husbands' or wives' expectations were more likely to be
      realized in cases of disagreement, and factors associated with the realization of
      expectations. The results indicate that couples expecting joint retirement were
      over three times more likely to retire jointly than couples in which neither
      spouse expected to do so. However, the probability of joint retirement did not
      differ between couples in which both spouses expected to retire jointly and those
      in which only one spouse expected to do so. Wives' and husbands' expectations
      were equally strong predictors of joint retirement, and retirement age, health,
      spouses' relative earnings, and discussions of retirement were related to the
      likelihood of realizing joint retirement expectations.

PMID- 20808728
TI  - Regularization Paths for Generalized Linear Models via Coordinate Descent.
AB  - We develop fast algorithms for estimation of generalized linear models with
      convex penalties. The models include linear regression, two-class logistic
      regression, and multinomial regression problems while the penalties include l(1)
      (the lasso), l(2) (ridge regression) and mixtures of the two (the elastic net).
      The algorithms use cyclical coordinate descent, computed along a regularization
      path. The methods can handle large problems and can also deal efficiently with
      sparse features. In comparative timings we find that the new algorithms are
      considerably faster than competing methods.

PMID- 20808730
TI  - Role of functional single nucleotide polymorphisms of MMP1, MMP2, and MMP9 in
      open angle glaucomas.
AB  - PURPOSE: Matrix metalloproteinases (MMPs) play an essential role in the turnover
      of the extracellular matrix and cellular behavior. MMP1, MMP2, and MMP9 have
      previously been implicated in the pathogenesis of primary open angle glaucoma
      (POAG) and open angle glaucoma secondary to exfoliation syndrome (XFG),
      respectively. Functional gene polymorphisms of these MMPs such as MMP1 -1607
      1G/2G (rs1799750), MMP2 -1306 C/T (rs243865), MMP2 -1575 G/A (rs243866), and MMP9
      Q279R (rs17576) are thus plausible candidates as risk factors for open angle
      glaucomas. The purpose of the present study was to investigate hypothesized
      associations between these polymorphisms and the presence of POAG and XFG in a
      Caucasian population. METHODS: The present case-control study included 322
      patients with POAG, 202 patients with XFG, and 248 control subjects. Genotyping
      of polymorphisms was done using polymerase chain reaction. RESULTS: No
      significant differences in either genotype distributions or allelic frequencies
      of MMP1 -1607 1G/2G, MMP2 -1306 C/T, MMP2 -1575 G/A, and MMP9 Q279R were found
      between patients with POAG and control subjects and patients with XFG and control
      subjects, respectively (p>0.05). The presence of POAG or XFG was not predicted by
      any of the investigated polymorphisms. CONCLUSIONS: Our data suggest that the
      MMP1 -1607 1G/2G, MMP2 -1306 C/T, MMP2 -1575 G/A, and MMP9 Q279R polymorphisms
      themselves are unlikely major risk factors among Caucasian patients with either
      POAG or XFG.

PMID- 20808729
TI  - Expression changes in DNA repair enzymes and mitochondrial DNA damage in aging
      rat lens.
AB  - PURPOSE: To determine if there is increased mitochondrial DNA (mtDNA) and nuclear
      DNA (nDNA) damage with age in the lenses of rats. We also explored the
      immunolocalization of 8-oxoguanine DNA glycosylase 1 (OGG1) and AP endonuclease 1
      (APE1) in the lens and studied three of the predominant base excision repair
      (BER) enzymes: OGG1, APE1, and DNA polymerase gamma (Polgamma). METHODS: The
      methods used by this study include the selection of twenty-six male Wistar rats
      in each group (2 months old and 26 months old) and fourteen male Wistar rats in
      the 16 months old group. The total DNA of lenses were isolated and the DNA genome
      was amplified by a long extension-polymerase chain reaction (LX-PCR). We examined
      mtDNA and nDNA damage with a quantitative polymerase chain reaction (QPCR) assay
      that was combined with EvaGreen. We also studied the gene expression of mRNA and
      protein in these key BER enzymes with real time-polymerase chain reaction (RT
      PCR) and western blot analysis. RESULTS: There was an increase in oxidative DNA
      damage, which exists primarily in the mtDNA. The amount of 8-hydroxy-2'-deoxy
      guanosine (8-OHdG) in DNA was significantly increased with age. Our experiments
      demonstrated that the gene expression of mRNA and protein in these key BER
      enzymes decreased with age. OGG1 and APE1 were localized by immunohistochemistry
      within lens epithelial cells (LECs) and superficial fiber cells. CONCLUSIONS: The
      gene expression of mRNA and protein in these key BER enzymes decreased with age,
      which caused a decrease in the repairing capability of the mtDNA and the
      accumulation of mtDNA damage. The increased mtDNA damage and decreased expression
      of BER enzymes may cause a "vicious cycle" of oxidative stress that contributes
      to the accumulation of mtDNA mutations and age-related cataract pathogenesis.

PMID- 20808731
TI  - Lack of association of the WRN C1367T polymorphism with senile cataract in the
      Israeli population.
AB  - PURPOSE: Werner syndrome is an autosomal recessive disease of premature aging
      caused by a polymorphic C1367T mutation in the Werner (WRN) gene. Although there
      are differences between the pathobiology of normal aging and the phenotype of
      Werner syndrome, the clinical age-related changes are similar. The aim of the
      study was to investigate the incidence of the C1367T (rs1346044) polymorphism in
      patients with age-related cataract. METHODS: The study group consisted of 81
      patients with senile cataract undergoing cataract extraction surgery. Data on
      age, sex, and medical history of microvascular disease and cancer were obtained
      from the medical files. Anterior lens capsule material was collected during
      surgery. DNA was extracted, amplified by polymerase chain reaction, and screened
      for the C1367T polymorphism in WRN using restriction enzymes followed by
      sequencing. RESULTS: There were 33 male and 48 female patients of mean age 74.3+/
      9 years. Genotypic frequencies were 67% for TT and 33% for TC. None of the
      patients had the CC genotype. Ten patients had a history of myocardial infarct, 8
      cerebrovascular accident, and 8 various tumors. The distribution of these
      morbidities was similar in the two genotype groups. CONCLUSIONS: The distribution
      of the C1367T WRN polymorphism in patients with senile cataract is similar to
      that in the normal population. Cataract formation in the elderly is not linked to
      a WRN mutation.

PMID- 20808732
TI  - Light-dependant intraretinal ion regulation by melanopsin in young awake and free
      moving mice evaluated with manganese-enhanced MRI.
AB  - PURPOSE: To test the hypothesis that in young, functionally blind mice, light
      dependent intraretinal ion regulation occurs via melanopsin. METHODS: Postnatal
      day (P) 7 wild type (WT, C57Bl/6) and melanopsin knockout (KO, opn4-/-, B6129)
      mice were light or dark adapted. Awake and freely moving animals were injected
      intraperitoneally (ip) with MnCl(2). Four hours later, the mice in both groups
      were anesthetized and studied with manganese-enhanced MRI (MEMRI) to measure the
      extent of intraretinal uptake of manganese and whole retinal thicknesses.
      RESULTS: In control P7 mice, light exposure increased (p<0.05) retinal manganese
      uptake over that in dark. This difference was observed throughout most of the
      retina. In P7 KO mice, intraretinal manganese uptake did not differ from that in
      age-matched dark-adapted WT mice, and was not light-dependent. No differences in
      whole retinal thickness were noted between groups. CONCLUSIONS: First time
      evidence is presented which demonstrates intraretinal ion regulation by
      melanopsin in vivo.

PMID- 20808733
TI  - Cross-cultural adaptation of the Child Depression Inventory for use in Tanzania
      with children affected by HIV.
AB  - Understanding the impact of the acquired immune deficiency syndrome (AIDS)
      epidemic is critical for developing appropriate interventions to create
      supportive environments for orphans and vulnerable children (OVC). Unfortunately,
      there are very few studies on the psychosocial wellbeing of children orphaned by
      AIDS in Africa, and even fewer in Tanzania. It has been difficult to make
      generalizations across studies and to identify and track children suffering from
      mental health difficulties, given the lack of culturally sensitive, standardized
      screening scales and diagnostic procedures. As a contribution to filling that
      gap, the current study demonstrates the applicability of an existing depression
      screening instrument (CDI) to evaluate both the needs of OVC as well as the
      effectiveness of interventions designed to support them.

PMID- 20808734
TI  - An Emotional Exposure-Based Treatment of Traumatic Stress for People with Chronic
      Pain: Preliminary Results for Fibromyalgia Syndrome.
AB  - Emotional trauma occurs in many patients with chronic pain, particularly
      fibromyalgia syndrome (FMS). Current cognitive-behavioral treatments for chronic
      pain have limited effects, perhaps because the trauma is not addressed, whereas
      emotional exposure-based treatments improve post-traumatic stress, but have not
      been tested on chronic pain. We present a novel, brief treatment protocol for
      people with chronic pain and unresolved trauma (Multi-Stimulus, Multi-Technique
      Emotional Exposure Therapy), which involves detecting avoidance of a range of
      emotion-related stimuli, implementing exposure techniques tailored to the
      patient's avoidances, and negotiating the process and therapeutic alliance. This
      treatment was pilot tested on 10 women with intractable FMS and trauma histories.
      Three months post-treatment, the sample showed moderate to large effects on
      stress symptoms, FMS impact, and emotional distress; and small to moderate
      improvements on pain and disability. Two patients showed substantial improvement,
      four made moderate gains, two showed modest improvement, and two did not benefit.
      This pilot study suggests that emotional exposure treatment for unresolved trauma
      may benefit some patients with FMS. Controlled testing of the treatment for FMS
      and other chronic pain populations is indicated.

PMID- 20808735
TI  - Psychosocial Functioning in Youth with Barth Syndrome.
AB  - This pilot study assessed the quality of life and psychosocial functioning of
      pediatric patients with Barth Syndrome. Thirty-four boys with Barth Syndrome and
      22 healthy male controls were administered a measure of verbal ability and
      completed measures of quality of life, loneliness, perceived peer support, and
      sibling relationship quality. Parents completed measures of parental distress,
      parenting stress, child academic functioning, child adaptive behavior, and child
      emotional and behavioral functioning. Quality of life ratings were consistently
      lower in youth with Barth Syndrome relative to both healthy controls and a
      previously reported sample of youth with cardiac disease. Compared to healthy
      controls, children with Barth Syndrome were rated as having more internalizing
      and externalizing symptoms, social problems, loneliness, and lower independent
      functioning. Parents of boys with Barth Syndrome reported greater distress and
      parenting stress relative to healthy controls. In addition, parents reported a
      significant need for academic accommodations, given their son's illness and
      associated impairments. Boys with Barth Syndrome and their parents appear to be
      affected by the presence of the illness in numerous ways. Results suggest the
      need for interventions aimed at helping children and families cope with illness
      related stressors to enhance quality of life and overall functioning.

PMID- 20808737
TI  - Summary of the 2009 annual sports symposium, expanding the toolbox: equipping
      ourselves with advanced treatment updates.

PMID- 20808736
TI  - On the rate of convergence of the maximum like-lihood estimator of a k-monotone
      density.
AB  - Bounds for the bracketing entropy of the classes of bounded k-monotone functions
      on [0, A] are obtained under both the Hellinger distance and the L(p)(Q)
      distance, where 1 <= p < infinity and Q is a probability measure on [0, A]. The
      result is then applied to obtain the rate of convergence of the maximum
      likelihood estimator of a k-monotone density.

PMID- 20808738
TI  - A message from the College on Forensic Sciences.

PMID- 20808739
TI  - The American Chiropractic Board of Sports Physicians wishes to congratulate the
      following doctors for receiving their DACBSP and CCSP certifications in 2008.

PMID- 20808741
TI  - Use of botulinum toxin in cheiloplasty: A new method to decrease tension.
AB  - OBJECTIVE: To determine if the use of botulinum toxin during cheiloplasty could
      help in the management of tension at the surgical wound level. INTERVENTIONS:
      Five children younger than six months of age, who were born with complete cleft
      lip and palate, were treated with a dose of 10 units of botulinum toxin injected
      into the upper lip during surgery. Before the surgery, an electromyographic study
      was carried out on the patients' upper lips. A Millard-type cheiloplasty was
      performed and 10 days later, a second electromyographic study was performed on
      the upper lips of all the patients. RESULTS: There was a significant change
      (P<0.039) in the electromyographic tracing obtained after the application of
      botulinum toxin, especially during rest. CONCLUSION: As confirmed by
      electromyography, botulinum toxin effectively inhibits the action of the
      orbicularis oris muscle, especially when at rest; consequently, the tension is
      decreased at the level of the surgical wound.

PMID- 20808742
TI  - Reversed dorsal metatarsal artery flap for reconstruction of a soft tissue defect
      of the big toe.
AB  - Soft tissue defects of the great toe that include exposed tendon and bone present
      a reconstructive challenge for plastic surgeons. A distally based dorsalis pedis
      island flap based on the first dorsal metatarsal artery, which has been
      successfully used to cover the soft tissue defect following wide excision of
      melanoma of the big toe, is reported.

PMID- 20808743
TI  - Facial cysts - Minimizing the scars.

PMID- 20808744
TI  - Saving the failing wound.

PMID- 20808745
TI  - Blepharoplasty using an attractive assistant.

PMID- 20808746
TI  - Trigger fingers: A checkmark incision.

PMID- 20808747
TI  - Anatomical variations of the carpal tunnel structures.
AB  - There are many anatomical variations in and around the carpal tunnel that affect
      the nerves, tendons and arteries in this area. Awareness of these variations is
      important both during the clinical examination and during carpal tunnel release.
      The purpose of the present review is to highlight recognized anatomical
      variations within the carpal tunnel including variation in nerve anatomy, tendon
      anatomical variants, vascular anatomical variations and muscle anatomical
      variations.

PMID- 20808748
TI  - Reconstruction of sacral defects following necrosis of buttocks due to
      embolization of internal iliac artery using a transverse lumbar flap.
AB  - Fractures of the pelvis associated with uncontrollable hypotension are managed by
      stabilization of fractures and arteriographic embolization of the bleeding
      vessels. Embolization of these arteries may result in necrosis of the buttocks.
      The use of a transverse lumbar artery-based flap can be used for repair of these
      defects.

PMID- 20808749
TI  - Aesthetic plastic surgery symposium, toronto, ontario, april 17-18, 2009.

PMID- 20808750
TI  - Nipple reduction - An adjunct to augmentation mammaplasty.
AB  - Nipple hypertrophy is an occasional deformity in Asians and a rare one in
      Caucasians. Lately, it has been showing up more often in plastic surgeons'
      offices across North America and elsewhere, owing to the influx of Asian
      immigration worldwide, as well as to the rising interest in esthetic surgery
      among Asian communities.A simplified technique for nipple reduction is described
      herein. It is very easy to execute, delivers accurate results and is extremely
      safe. It tackles both the excessive 'projection' and the less frequent excessive
      'width' of the nipple. It may be used separately or incorporated as an adjunct to
      mammary augmentation or mastopexy. Excellent esthetic results are obtained, while
      both the nipple innervation and its lactiferous ducts are preserved. The
      patient's and surgeon's satisfaction is high.

PMID- 20808751
TI  - Complications from injectable materials used for breast augmentation.
AB  - Fewer surgical procedures have a history as fascinating and as terrifying as
      breast augmentation. Initial efforts at augmentation involved injection of
      substances such as paraffin or oil into the breast tissue, or the implantation of
      substances including ivory or glass balls, or rubber. More recent efforts have
      included the injection of liquid silicone or polyacrylamide hydrogel. The current
      paper reviews four distinct eras of breast augmentation, and provides the current
      status of these injection materials. A case report is presented on a woman whose
      breasts were injected with polyacrylamide hydrogel in Iran. The current status of
      this group of materials is also presented. During the past 110 years, history has
      repeated itself during each of the four eras of injection.

PMID- 20808752
TI  - Infrared surface temperature monitoring in the postoperative management of free
      tissue transfers.
AB  - BACKGROUND: Early identification of failing free flaps may allow for potential
      intervention and flap salvage. The predictive ability of flap temperature
      monitoring has been previously questioned. The present study investigated the
      ability of an infrared surface temperature monitoring device to detect trends in
      flap temperature and correlation with anastomotic thrombosis and flap failure.
      METHODS: Postoperative measurement of surface temperature was obtained in 47
      microvascular free flaps. Differences in temperature between survival and failure
      groups were evaluated for statistical significance using Student's t test
      (P<0.05). In addition, a single variable analysis was performed on 30 different
      flap characteristics to evaluate their prediction of flap failure. RESULTS: In
      total, eight flaps failed. Five of these were re-explored, of which one was
      salvaged. The three other flaps died a progressive death secondary to presumed
      thrombosis of the microcirculation despite adequate Doppler signals. Temperatures
      of the flap failure group during the last 24 h yielded a mean difference of 2
      degrees C (3.56 degrees F) compared with surviving flaps (P<0.05). The
      temperature of the failing flaps began to decline at the eighth postoperative
      hour. Single variable analysis identified prior radiation to be a predictor of
      flap failure. CONCLUSIONS: A surface temperature measurement device provides
      reproducible digital readings without physical contact with the flap. Technical
      difficulties encountered in previous research with implantable or surface contact
      temperature probes are obviated with this noncontact technique. Flap temperature
      monitoring revealed a trend in temperature that correlates with anastomotic
      thrombosis and eventual flap failure.

PMID- 20808753
TI  - Canadian Society for Aesthetic (Cosmetic) Plastic Surgery/Societe canadienne de
      chirurgie plastique esthetique: Abstracts presented at the 36th Annual Meeting
      September 11 and 12, 2009.

PMID- 20808759
TI  - Neurocysticercosis, a persisting health problem in Mexico.
AB  - BACKGROUND: The ongoing epidemiological transition in Mexico minimizes the
      relative impact of neurocysticercosis (NC) on public health. However, hard data
      on the disease frequency are not available. METHODOLOGY: All clinical records
      from patients admitted in the Instituto Nacional de Neurologia y Neurocirugia
      (INNN) at Mexico City in 1994 and 2004 were revised. The frequencies of
      hospitalized NC patients in neurology, neurosurgery and psychiatry services, as
      well as NC mortality from 1995 through 2009, were retrieved. Statistical analyses
      were made to evaluate possible significant differences in frequencies of NC
      patients' admission between 1994 and 2004, and in yearly frequencies of NC
      patients' hospitalization and death between 1995 and 2009. PRINCIPAL FINDINGS: NC
      frequency in INNN is not significantly different in 1994 and 2004. Between these
      two years, clinical severity of the cases diminished and the proportion of
      patients living in Mexico City increased. Yearly frequencies of hospitalization
      in neurology and psychiatry services were stable, while frequencies of
      hospitalization in neurosurgery service and mortality significantly decreased
      between 1995 and 2009. CONCLUSIONS: Our findings show a stable tendency of
      hospital cases during the last decade that should encourage to redouble efforts
      to control this ancient disease.

PMID- 20808760
TI  - Tyrosine-phosphorylated caveolin-1 blocks bacterial uptake by inducing Vav2-RhoA
      mediated cytoskeletal rearrangements.
AB  - Certain bacterial adhesins appear to promote a pathogen's extracellular lifestyle
      rather than its entry into host cells. However, little is known about the stimuli
      elicited upon such pathogen host-cell interactions. Here, we report that type IV
      pili (Tfp)-producing Neisseria gonorrhoeae (P(+)GC) induces an immediate
      recruitment of caveolin-1 (Cav1) in the host cell, which subsequently prevents
      bacterial internalization by triggering cytoskeletal rearrangements via
      downstream phosphotyrosine signaling. A broad and unbiased analysis of potential
      interaction partners for tyrosine-phosphorylated Cav1 revealed a direct
      interaction with the Rho-family guanine nucleotide exchange factor Vav2. Both
      Vav2 and its substrate, the small GTPase RhoA, were found to play a direct role
      in the Cav1-mediated prevention of bacterial uptake. Our findings, which have
      been extended to enteropathogenic Escherichia coli, highlight how Tfp-producing
      bacteria avoid host cell uptake. Further, our data establish a mechanistic link
      between Cav1 phosphorylation and pathogen-induced cytoskeleton reorganization and
      advance our understanding of caveolin function.

PMID- 20808761
TI  - Ginkgo biloba extract ameliorates oxidative phosphorylation performance and
      rescues abeta-induced failure.
AB  - BACKGROUND: Energy deficiency and mitochondrial failure have been recognized as a
      prominent, early event in Alzheimer's disease (AD). Recently, we demonstrated
      that chronic exposure to amyloid-beta (Abeta) in human neuroblastoma cells over
      expressing human wild-type amyloid precursor protein (APP) resulted in (i)
      activity changes of complexes III and IV of the oxidative phosphorylation system
      (OXPHOS) and in (ii) a drop of ATP levels which may finally instigate loss of
      synapses and neuronal cell death in AD. Therefore, the aim of the present study
      was to investigate whether standardized Ginkgo biloba extract LI 1370 (GBE) is
      able to rescue Abeta-induced defects in energy metabolism. METHODOLOGY/PRINCIPAL
      FINDINGS: We used a high-resolution respiratory protocol to evaluate OXPHOS
      respiratory capacity under physiological condition in control (stably transfected
      with the empty vector) and APP cells after treatment with GBE. In addition,
      oxygen consumption of isolated mitochondria, activities of mitochondrial
      respiratory enzymes, ATP and reactive oxygen species (ROS) levels as well as
      mitochondrial membrane mass and mitochondrial DNA content were determined. We
      observed a general antioxidant effect of GBE leading to an increase of the
      coupling state of mitochondria as well as energy homeostasis and a reduction of
      ROS levels in control cells and in APP cells. GBE effect on OXPHOS was even
      preserved in mitochondria after isolation from treated cells. Moreover, these
      functional data were paralleled by an up-regulation of mitochondrial DNA.
      Improvement of the OXPHOS efficiency was stronger in APP cells than in control
      cells. In APP cells, the GBE-induced amelioration of oxygen consumption most
      likely arose from the modulation and respective normalization of the Abeta
      induced disturbance in the activity of mitochondrial complexes III and IV
      restoring impaired ATP levels possibly through decreasing Abeta and oxidative
      stress level. CONCLUSIONS/SIGNIFICANCE: Although the underlying molecular
      mechanisms of the mode of action of GBE remain to be determined, our study
      clearly highlights the beneficial effect of GBE on the cellular OXPHOS
      performance and restoration of Abeta-induced mitochondrial dysfunction.

PMID- 20808762
TI  - A critical analysis of Atoh7 (Math5) mRNA splicing in the developing mouse
      retina.
AB  - The Math5 (Atoh7) gene is transiently expressed during retinogenesis by
      progenitors exiting mitosis, and is essential for ganglion cell (RGC)
      development. Math5 contains a single exon, and its 1.7 kb mRNA encodes a 149-aa
      polypeptide. Mouse Math5 mutants have essentially no RGCs or optic nerves. Given
      the importance of this gene in retinal development, we thoroughly investigated
      the possibility of Math5 mRNA splicing by Northern blot, 3'RACE, RNase protection
      assays, and RT-PCR, using RNAs extracted from embryonic eyes and adult
      cerebellum, or transcribed in vitro from cDNA clones. Because Math5 mRNA contains
      an elevated G+C content, we used graded concentrations of betaine, an
      isostabilizing agent that disrupts secondary structure. Although approximately
      10% of cerebellar Math5 RNAs are spliced, truncating the polypeptide, our results
      show few, if any, spliced Math5 transcripts exist in the developing retina (<1%).
      Rare deleted cDNAs do arise via RT-mediated RNA template switching in vitro, and
      are selectively amplified during PCR. These data differ starkly from a recent
      study (Kanadia and Cepko 2010), which concluded that the vast majority of Math5
      and other bHLH transcripts are spliced to generate noncoding RNAs. Our findings
      clarify the architecture of the Math5 gene and its mechanism of action. These
      results have implications for all members of the bHLH gene family, for any gene
      that is alternatively spliced, and for the interpretation of all RT-PCR
      experiments.

PMID- 20808763
TI  - The Onchocerca volvulus cysteine proteinase inhibitor, Ov-CPI-2, is a target of
      protective antibody response that increases with age.
AB  - BACKGROUND: Despite considerable efforts, a suitable vaccine against Onchocerca
      volvulus infection has remained elusive. Herein, we report on the use of
      molecular tools to identify and characterize O. volvulus antigens that are
      possibly associated with the development of concomitant immunity in
      onchocerciasis. METHODOLOGY/PRINCIPAL FINDINGS: Third-stage larvae (L3) and
      molting L3 (mL3) O. volvulus stage-specific cDNA libraries were screened with a
      pool of sera from chronically infected patients who had likely developed such
      immunity. The 87 immunoreactive clones isolated were grouped into 20 distinct
      proteins of which 12 had already been cloned and/or characterized before and 4
      had been proven to be protective in a small O. volvulus animal model. One of
      these, onchocystatin (Ov-CPI-2), a previously characterized O. volvulus cysteine
      proteinase inhibitor was, overall, the most abundant clone recognized by the
      immune sera in both the L3 and mL3 cDNA libraries. To further characterize its
      association with protective immunity, we measured the IgG subclass and IgE class
      specific responses to the antigen in putatively immune (PI) and infected (INF)
      individuals living in a hyperendemic area in Cameroon. It appeared that both
      groups had similar IgG3 and IgE responses to the antigen, but the INF had
      significantly higher IgG1 and IgG4 responses than the PI individuals (p<0.05). In
      the INF group, the IgG3 levels increased significantly with the age of the
      infected individuals (r = 0.241; p<0.01). The IgG1 responses in the INF were high
      regardless of age. Notably, culturing L3 in vitro in the presence of anti-Ov-CPI
      2 monospecific human antibodies and naive neutrophils resulted in almost complete
      inhibition of molting of L3 to L4 and to cytotoxicity to the larvae.
      CONCLUSIONS/SIGNIFICANCE: These results add to the knowledge of protective
      immunity in onchocerciasis and support the possible involvement of anti-Ov-CPI-2
      IgG1 and/or IgG3 cytophilic antibodies in the development of protective immunity
      in the PI and the INF. The results further support the consideration of Ov-CPI-2
      as a leading target for an anti-L3 vaccine.

PMID- 20808764
TI  - Identifying molecular effects of diet through systems biology: influence of
      herring diet on sterol metabolism and protein turnover in mice.
AB  - BACKGROUND: Changes in lifestyle have resulted in an epidemic development of
      obesity-related diseases that challenge the healthcare systems worldwide. To
      develop strategies to tackle this problem the focus is on diet to prevent the
      development of obesity-associated diseases such as cardiovascular disease (CVD).
      This will require methods for linking nutrient intake with specific metabolic
      processes in different tissues. METHODOLOGY/PRINCIPAL FINDING: Low-density
      lipoprotein receptor-deficient (Ldlr -/-) mice were fed a high fat/high sugar
      diet to mimic a westernized diet, being a major reason for development of obesity
      and atherosclerosis. The diets were supplemented with either beef or herring, and
      matched in macronutrient contents. Body composition, plasma lipids and aortic
      lesion areas were measured. Transcriptomes of metabolically important tissues,
      e.g. liver, muscle and adipose tissue were analyzed by an integrated approach
      with metabolic networks to directly map the metabolic effects of diet in these
      different tissues. Our analysis revealed a reduction in sterol metabolism and
      protein turnover at the transcriptional level in herring-fed mice. CONCLUSION:
      This study shows that an integrated analysis of transcriptome data using
      metabolic networks resulted in the identification of signature pathways. This
      could not have been achieved using standard clustering methods. In particular,
      this systems biology analysis could enrich the information content of biomedical
      or nutritional data where subtle changes in several tissues together affects body
      metabolism or disease progression. This could be applied to improve diets for
      subjects exposed to health risks associated with obesity.

PMID- 20808765
TI  - Colorimetric measurement of triglycerides cannot provide an accurate measure of
      stored fat content in Drosophila.
AB  - Drosophila melanogaster has recently emerged as a useful model system in which to
      study the genetic basis of regulation of fat storage. One of the most frequently
      used methods for evaluating the levels of stored fat (triglycerides) in flies is
      a coupled colorimetric assay available as a kit from several manufacturers. This
      is an aqueous-based enzymatic assay that is normally used for measurement of
      mammalian serum triglycerides, which are present in soluble lipoprotein
      complexes. In this short communication, we show that coupled colorimetric assay
      kits cannot accurately measure stored triglycerides in Drosophila. First, they
      fail to give accurate readings when tested on insoluble triglyceride mixtures
      with compositions like that of stored fat, or on fat extracted from flies with
      organic solvents. This is probably due to an inability of the lipase used in the
      kits to efficiently cleave off the glycerol head group from fat molecules in
      insoluble samples. Second, the measured final products of the kits are
      quinoneimines, which absorb visible light in the same wavelength range as
      Drosophila eye pigments. Thus, when extracts from crushed flies are assayed, much
      of the measured signal is actually due to eye pigments. Finally, the lipoprotein
      lipases used in colorimetric assays also cleave non-fat glycerides. The glycerol
      backbones liberated from all classes of glycerides are measured through the
      remaining reactions in the assay. As a consequence, when these assay kits are
      used to evaluate tissue extracts, the observed signal actually represents the
      amount of free glycerols together with all types of glycerides. For these
      reasons, findings obtained through use of coupled colorimetric assays on
      Drosophila samples must be interpreted with caution. We also show here that using
      thin-layer chromatography to measure stored triglycerides in flies eliminates all
      of these problems.

PMID- 20808767
TI  - Establishment of fruit bat cells (Rousettus aegyptiacus) as a model system for
      the investigation of filoviral infection.
AB  - BACKGROUND: The fruit bat species Rousettus aegyptiacus was identified as a
      potential reservoir for the highly pathogenic filovirus Marburg virus. To
      establish a basis for a molecular understanding of the biology of filoviruses in
      the reservoir host, we have adapted a set of molecular tools for investigation of
      filovirus replication in a recently developed cell line, R06E, derived from the
      species Rousettus aegyptiacus. METHODOLOGY/PRINCIPAL FINDINGS: Upon infection
      with Ebola or Marburg viruses, R06E cells produced viral titers comparable to
      VeroE6 cells, as shown by TCID(50) analysis. Electron microscopic analysis of
      infected cells revealed morphological signs of filovirus infection as described
      for human- and monkey-derived cell lines. Using R06E cells, we detected an
      unusually high amount of intracellular viral proteins, which correlated with the
      accumulation of high numbers of filoviral nucleocapsids in the cytoplasm. We
      established protocols to produce Marburg infectious virus-like particles from
      R06E cells, which were then used to infect naive target cells to investigate
      primary transcription. This was not possible with other cell lines previously
      tested. Moreover, we established protocols to reliably rescue recombinant Marburg
      viruses from R06E cells. CONCLUSION/SIGNIFICANCE: These data indicated that R06E
      cells are highly suitable to investigate the biology of filoviruses in cells
      derived from their presumed reservoir.

PMID- 20808766
TI  - Identification of attractive drug targets in neglected-disease pathogens using an
      in silico approach.
AB  - BACKGROUND: The increased sequencing of pathogen genomes and the subsequent
      availability of genome-scale functional datasets are expected to guide the
      experimental work necessary for target-based drug discovery. However, a major
      bottleneck in this has been the difficulty of capturing and integrating relevant
      information in an easily accessible format for identifying and prioritizing
      potential targets. The open-access resource TDRtargets.org facilitates drug
      target prioritization for major tropical disease pathogens such as the
      mycobacteria Mycobacterium leprae and Mycobacterium tuberculosis; the
      kinetoplastid protozoans Leishmania major, Trypanosoma brucei, and Trypanosoma
      cruzi; the apicomplexan protozoans Plasmodium falciparum, Plasmodium vivax, and
      Toxoplasma gondii; and the helminths Brugia malayi and Schistosoma mansoni.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we present strategies to prioritize pathogen
      proteins based on whether their properties meet criteria considered desirable in
      a drug target. These criteria are based upon both sequence-derived information
      (e.g., molecular mass) and functional data on expression, essentiality,
      phenotypes, metabolic pathways, assayability, and druggability. This approach
      also highlights the fact that data for many relevant criteria are lacking in less
      studied pathogens (e.g., helminths), and we demonstrate how this can be partially
      overcome by mapping data from homologous genes in well-studied organisms. We also
      show how individual users can easily upload external datasets and integrate them
      with existing data in TDRtargets.org to generate highly customized ranked lists
      of potential targets. CONCLUSIONS/SIGNIFICANCE: Using the datasets and the tools
      available in TDRtargets.org, we have generated illustrative lists of potential
      drug targets in seven tropical disease pathogens. While these lists are broadly
      consistent with the research community's current interest in certain specific
      proteins, and suggest novel target candidates that may merit further study, the
      lists can easily be modified in a user-specific manner, either by adjusting the
      weights for chosen criteria or by changing the criteria that are included.

PMID- 20808768
TI  - Novel naphthalene-based inhibitors of Trypanosoma brucei RNA editing ligase 1.
AB  - BACKGROUND: Neglected tropical diseases, including diseases caused by
      trypanosomatid parasites such as Trypanosoma brucei, cost tens of millions of
      disability-adjusted life-years annually. As the current treatments for African
      trypanosomiasis and other similar infections are limited, new therapeutics are
      urgently needed. RNA Editing Ligase 1 (REL1), a protein unique to trypanosomes
      and other kinetoplastids, was identified recently as a potential drug target.
      METHODOLOGY/PRINCIPAL FINDINGS: Motivated by the urgent need for novel
      trypanocidal therapeutics, we use an ensemble-based virtual-screening approach to
      discover new naphthalene-based TbREL1 inhibitors. The predicted binding modes of
      the active compounds are evaluated within the context of the flexible receptor
      model and combined with computational fragment mapping to determine the most
      likely binding mechanisms. Ultimately, four new low-micromolar inhibitors are
      presented. Three of the four compounds may bind to a newly revealed cleft that
      represents a putative druggable site not evident in any crystal structure.
      CONCLUSIONS/SIGNIFICANCE: Pending additional optimization, the compounds
      presented here may serve as precursors for future novel therapies useful in the
      fight against several trypanosomatid pathogens, including human African
      trypanosomiasis, a devastating disease that afflicts the vulnerable patient
      populations of sub-Saharan Africa.

PMID- 20808769
TI  - A complete developmental sequence of a Drosophila neuronal lineage as revealed by
      twin-spot MARCM.
AB  - Drosophila brains contain numerous neurons that form complex circuits. These
      neurons are derived in stereotyped patterns from a fixed number of progenitors,
      called neuroblasts, and identifying individual neurons made by a neuroblast
      facilitates the reconstruction of neural circuits. An improved MARCM (mosaic
      analysis with a repressible cell marker) technique, called twin-spot MARCM,
      allows one to label the sister clones derived from a common progenitor
      simultaneously in different colors. It enables identification of every single
      neuron in an extended neuronal lineage based on the order of neuron birth. Here
      we report the first example, to our knowledge, of complete lineage analysis among
      neurons derived from a common neuroblast that relay olfactory information from
      the antennal lobe (AL) to higher brain centers. By identifying the sequentially
      derived neurons, we found that the neuroblast serially makes 40 types of AL
      projection neurons (PNs). During embryogenesis, one PN with multi-glomerular
      innervation and 18 uniglomerular PNs targeting 17 glomeruli of the adult AL are
      born. Many more PNs of 22 additional types, including four types of
      polyglomerular PNs, derive after the neuroblast resumes dividing in early larvae.
      Although different offspring are generated in a rather arbitrary sequence, the
      birth order strictly dictates the fate of each post-mitotic neuron, including the
      fate of programmed cell death. Notably, the embryonic progenitor has an altered
      temporal identity following each self-renewing asymmetric cell division. After
      larval hatching, the same progenitor produces multiple neurons for each cell
      type, but the number of neurons for each type is tightly regulated. These
      observations substantiate the origin-dependent specification of neuron types.
      Sequencing neuronal lineages will not only unravel how a complex brain develops
      but also permit systematic identification of neuron types for detailed structure
      and function analysis of the brain.

PMID- 20808770
TI  - Positive feedback between mycorrhizal fungi and plants influences plant invasion
      success and resistance to invasion.
AB  - Negative or positive feedback between arbuscular mycorrhizal fungi (AMF) and host
      plants can contribute to plant species interactions, but how this feedback
      affects plant invasion or resistance to invasion is not well known. Here we
      tested how alterations in AMF community induced by an invasive plant species
      generate feedback to the invasive plant itself and affect subsequent interactions
      between the invasive species and its native neighbors. We first examined the
      effects of the invasive forb Solidago canadensis L. on AMF communities comprising
      five different AMF species. We then examined the effects of the altered AMF
      community on mutualisms formed with the native legume forb species Kummerowia
      striata (Thunb.) Schindl. and on the interaction between the invasive and native
      plants. The host preferences of the five AMF were also assessed to test whether
      the AMF form preferred mutualistic relations with the invasive and/or the native
      species. We found that S. canadensis altered AMF spore composition by increasing
      one AMF species (Glomus geosporum) while reducing Glomus mosseae, which is the
      dominant species in the field. The host preference test showed that S. canadensis
      had promoted the abundance of AMF species (G. geosporum) that most promoted its
      own growth. As a consequence, the altered AMF community enhanced the
      competitiveness of invasive S. canadensis at the expense of K. striata. Our
      results demonstrate that the invasive S. canadensis alters soil AMF community
      composition because of fungal-host preference. This change in the composition of
      the AMF community generates positive feedback to the invasive S. canadensis
      itself and decreases AM associations with native K. striata, thereby making the
      native K. striata less dominant.

PMID- 20808771
TI  - Dcas supports cell polarization and cell-cell adhesion complexes in development.
AB  - Mammalian Cas proteins regulate cell migration, division and survival, and are
      often deregulated in cancer. However, the presence of four paralogous Cas family
      members in mammals (BCAR1/p130Cas, EFS/Sin1, NEDD9/HEF1/Cas-L, and CASS4/HEPL)
      has limited their analysis in development. We deleted the single Drosophila Cas
      gene, Dcas, to probe the developmental function of Dcas. Loss of Dcas had limited
      effect on embryonal development. However, we found that Dcas is an important
      modulator of the severity of the developmental phenotypes of mutations affecting
      integrins (If and mew) and their downstream effectors Fak56D or Src42A.
      Strikingly, embryonic lethal Fak56D-Dcas double mutant embryos had extensive cell
      polarity defects, including mislocalization and reduced expression of E-cadherin.
      Further genetic analysis established that loss of Dcas modified the embryonal
      lethal phenotypes of embryos with mutations in E-cadherin (Shg) or its signaling
      partners p120- and beta-catenin (Arm). These results support an important role
      for Cas proteins in cell-cell adhesion signaling in development.

PMID- 20808772
TI  - A novel zinc finger protein Zfp277 mediates transcriptional repression of the
      Ink4a/arf locus through polycomb repressive complex 1.
AB  - BACKGROUND: Polycomb group (PcG) proteins play a crucial role in cellular
      senescence as key transcriptional regulators of the Ink4a/Arf tumor suppressor
      gene locus. However, how PcG complexes target and contribute to stable gene
      silencing of the Ink4a/Arf locus remains little understood. METHODOLOGY/PRINCIPAL
      FINDINGS: We examined the function of Zinc finger domain-containing protein 277
      (Zfp277), a novel zinc finger protein that interacts with the PcG protein Bmi1.
      Zfp277 binds to the Ink4a/Arf locus in a Bmi1-independent manner and interacts
      with polycomb repressor complex (PRC) 1 through direct interaction with Bmi1.
      Loss of Zfp277 in mouse embryonic fibroblasts (MEFs) caused dissociation of PcG
      proteins from the Ink4a/Arf locus, resulting in premature senescence associated
      with derepressed p16(Ink4a) and p19(Arf) expression. Levels of both Zfp277 and
      PcG proteins inversely correlated with those of reactive oxygen species (ROS) in
      senescing MEFs, but the treatment of Zfp277(-/-) MEFs with an antioxidant
      restored the binding of PRC2 but not PRC1 to the Ink4a/Arf locus. Notably, forced
      expression of Bmi1 in Zfp277(-/-) MEFs did not restore the binding of Bmi1 to the
      Ink4a/Arf locus and failed to bypass cellular senescence. A Zfp277 mutant that
      could not bind Bmi1 did not rescue Zfp277(-/-) MEFs from premature senescence.
      CONCLUSIONS/SIGNIFICANCE: Our findings implicate Zfp277 in the transcriptional
      regulation of the Ink4a/Arf locus and suggest that the interaction of Zfp277 with
      Bmi1 is essential for the recruitment of PRC1 to the Ink4a/Arf locus. Our
      findings also highlight dynamic regulation of both Zfp277 and PcG proteins by the
      oxidative stress pathways.

PMID- 20808773
TI  - Profiling and functional analyses of microRNAs and their target gene products in
      human uterine leiomyomas.
AB  - BACKGROUND: Human uterine leiomyomas (ULM) are characterized by dysregulation of
      a large number of genes and non-coding regulatory microRNAs. In order to identify
      microRNA::mRNA associations relevant to ULM pathogenesis, we examined global
      correlation patterns between the altered microRNA expression and the predicted
      target genes in ULMs and matched myometria. METHODOLOGY/PRINCIPAL FINDINGS:
      Patterns of inverse association of microRNA with mRNA expression in ULMs revealed
      an involvement of multiple candidate pathways, including extensive
      transcriptional reprogramming, cell proliferation control, MAP kinase, TGF-beta,
      WNT, JAK/STAT signaling, remodeling of cell adhesion, and cell-cell and cell
      matrix contacts. We further examined the correlation between the expression of
      the selected target gene protein products and microRNAs in thirty-six paired sets
      of leiomyomas and matched myometria. We found that a number of dysregulated
      microRNAs were inversely correlated with their targets at the protein level. The
      comparative genomic hybridization (CGH) in eight ULM patients revealed that
      partially shared deletions of two distinct chromosomal regions might be
      responsible for loss of cancer-associated microRNA expression and could thus
      contribute to the ULM pathogenesis via deregulation of target mRNAs. Last, we
      functionally tested the repressor effects of selected cancer-related microRNAs on
      their predicted target genes in vitro. CONCLUSIONS/SIGNIFICANCE: We found that
      some but not all of the predicted and inversely correlated target genes in ULMs
      can be directly regulated by microRNAs in vitro. Our findings provide a broad
      overview of molecular events underlying the tumorigenesis of uterine ULMs and
      identify select genetic and regulatory events that alter microRNA expression and
      may play important roles in ULM pathobiology by positively regulating tumor
      growth while maintaining the non-invasive character of ULMs.

PMID- 20808774
TI  - Miss to the right: the effect of attentional asymmetries on goal-kicking.
AB  - Cerebral asymmetries for spatial attention generate a bias of attention--causing
      lines to be bisected to the left or right in near (within reach) and far (outside
      reach) space, respectively. This study explored whether the rightward deviation
      for bisecting lines in far space extends to tasks where a ball is aimed between
      two goal-posts. Kicking was assessed in a laboratory and a real-life setting. In
      the laboratory setting, 212 participants carried out three conditions: (a) kick a
      soccer ball at a single goal post, (b) kick a soccer ball between two goal posts
      and (c) use a stick to indicate the middle between two goal posts. The goals were
      placed at a distance of 4.0 m. There was no deviation in the one-goal kicking
      condition--demonstrating that no asymmetries exist in the perceptual motor system
      when aiming at a single point. When kicking or pointing at the middle between two
      goal posts, rightward deviations were observed. In the real-world setting, the
      number of misses to the left or right of goal (behinds) in the Australian Rules
      football for the 2005-2009 seasons was assessed. The data showed more rightward
      deviations for kicks at goal. Combined, the studies suggest that the rightward
      deviation for lines placed in far space extends to the kicking of a football in
      laboratory and real-life settings. This asymmetry in kicking builds on a body of
      research showing that attentional asymmetries impact everyday activities.

PMID- 20808775
TI  - TRIM5 suppresses cross-species transmission of a primate immunodeficiency virus
      and selects for emergence of resistant variants in the new species.
AB  - Simian immunodeficiency viruses of sooty mangabeys (SIVsm) are the source of
      multiple, successful cross-species transmissions, having given rise to HIV-2 in
      humans, SIVmac in rhesus macaques, and SIVstm in stump-tailed macaques. Cellular
      assays and phylogenetic comparisons indirectly support a role for TRIM5alpha, the
      product of the TRIM5 gene, in suppressing interspecies transmission and emergence
      of retroviruses in nature. Here, we investigate the in vivo role of TRIM5
      directly, focusing on transmission of primate immunodeficiency viruses between
      outbred primate hosts. Specifically, we retrospectively analyzed experimental
      cross-species transmission of SIVsm in two cohorts of rhesus macaques and found a
      significant effect of TRIM5 genotype on viral replication levels. The effect was
      especially pronounced in a cohort of animals infected with SIVsmE543-3, where
      TRIM5 genotype correlated with approximately 100-fold to 1,000-fold differences
      in viral replication levels. Surprisingly, transmission occurred even in
      individuals bearing restrictive TRIM5 genotypes, resulting in attenuation of
      replication rather than an outright block to infection. In cell-culture assays,
      the same TRIM5 alleles associated with viral suppression in vivo blocked
      infectivity of two SIVsm strains, but not the macaque-adapted strain SIVmac239.
      Adaptations appeared in the viral capsid in animals with restrictive TRIM5
      genotypes, and similar adaptations coincide with emergence of SIVmac in captive
      macaques in the 1970s. Thus, host TRIM5 can suppress viral replication in vivo,
      exerting selective pressure during the initial stages of cross-species
      transmission.

PMID- 20808776
TI  - Dynamic disorder in quasi-equilibrium enzymatic systems.
AB  - Conformations and catalytic rates of enzymes fluctuate over a wide range of
      timescales. Despite these fluctuations, there exist some limiting cases in which
      the enzymatic catalytic rate follows the macroscopic rate equation such as the
      Michaelis-Menten law. In this paper we investigate the applicability of
      macroscopic rate laws for fluctuating enzyme systems in which catalytic
      transitions are slower than ligand binding-dissociation reactions. In this quasi
      equilibrium limit, for an arbitrary reaction scheme we show that the catalytic
      rate has the same dependence on ligand concentrations as obtained from mass
      action kinetics even in the presence of slow conformational fluctuations. These
      results indicate that the timescale of conformational dynamics--no matter how
      slow--will not affect the enzymatic rate in quasi-equilibrium limit. Our
      numerical results for two enzyme-catalyzed reaction schemes involving multiple
      substrates and inhibitors further support our general theory.

PMID- 20808777
TI  - TRIMming SIV Transmission between Species.

PMID- 20808779
TI  - "Mens sana in corpore sano": exercise and hypothalamic ER stress.

PMID- 20808778
TI  - GFAP-driven GFP expression in activated mouse Muller glial cells aligning retinal
      blood vessels following intravitreal injection of AAV2/6 vectors.
AB  - BACKGROUND: Muller cell gliosis occurs in various retinal pathologies regardless
      of the underlying cellular defect. Because activated Muller glial cells span the
      entire retina and align areas of injury, they are ideal targets for therapeutic
      strategies, including gene therapy. METHODOLOGY/PRINCIPAL FINDINGS: We used adeno
      associated viral AAV2/6 vectors to transduce mouse retinas. The transduction
      pattern of AAV2/6 was investigated by studying expression of the green
      fluorescent protein (GFP) transgene using scanning-laser ophthalmoscopy and
      immuno-histochemistry. AAV2/6 vectors transduced mouse Muller glial cells
      aligning the retinal blood vessels. However, the transduction capacity was
      hindered by the inner limiting membrane (ILM) and besides Muller glial cells,
      several other inner retinal cell types were transduced. To obtain Muller glial
      cell-specific transgene expression, the cytomegalovirus (CMV) promoter was
      replaced by the glial fibrillary acidic protein (GFAP) promoter. Specificity and
      activation of the GFAP promoter was tested in a mouse model for retinal gliosis.
      Mice deficient for Crumbs homologue 1 (CRB1) develop gliosis after light
      exposure. Light exposure of Crb1(-/-) retinas transduced with AAV2/6-GFAP-GFP
      induced GFP expression restricted to activated Muller glial cells aligning
      retinal blood vessels. CONCLUSIONS/SIGNIFICANCE: Our experiments indicate that
      AAV2 vectors carrying the GFAP promoter are a promising tool for specific
      expression of transgenes in activated glial cells.

PMID- 20808780
TI  - Mechanistic insights on the inhibition of c5 DNA methyltransferases by
      zebularine.
AB  - In mammals DNA methylation occurs at position 5 of cytosine in a CpG context and
      regulates gene expression. It plays an important role in diseases and inhibitors
      of DNA methyltransferases (DNMTs)--the enzymes responsible for DNA methylation-
      are used in clinics for cancer therapy. The most potent inhibitors are 5
      azacytidine and 5-azadeoxycytidine. Zebularine (1-(beta-D-ribofuranosyl)-2(1H)-
      pyrimidinone) is another cytidine analog described as a potent inhibitor that
      acts by forming a covalent complex with DNMT when incorporated into DNA. Here we
      bring additional experiments to explain its mechanism of action. First, we
      observe an increase in the DNA binding when zebularine is incorporated into the
      DNA, compared to deoxycytidine and 5-fluorodeoxycytidine, together with a strong
      decrease in the dissociation rate. Second, we show by denaturing gel analysis
      that the intermediate covalent complex between the enzyme and the DNA is
      reversible, differing thus from 5-fluorodeoxycytidine. Third, no methylation
      reaction occurs when zebularine is present in the DNA. We confirm that zebularine
      exerts its demethylation activity by stabilizing the binding of DNMTs to DNA,
      hindering the methylation and decreasing the dissociation, thereby trapping the
      enzyme and preventing turnover even at other sites.

PMID- 20808782
TI  - Rapid decision-making with side-specific perceptual discrimination in ants.
AB  - BACKGROUND: Timely decision making is crucial for survival and reproduction.
      Organisms often face a speed-accuracy trade-off, as fully informed, accurate
      decisions require time-consuming gathering and treatment of information. Optimal
      strategies for decision-making should therefore vary depending on the context. In
      mammals, there is mounting evidence that multiple systems of perceptual
      discrimination based on different neural circuits emphasize either fast responses
      or accurate treatment of stimuli depending on the context. METHODOLOGY/PRINCIPAL
      FINDINGS: We used the ant Camponotus aethiops to test the prediction that fast
      information processing achieved through direct neural pathways should be favored
      in situations where quick reactions are adaptive. Social insects discriminate
      readily between harmless group-members and dangerous strangers using easily
      accessible cuticular hydrocarbons as nestmate recognition cues. We show that i)
      tethered ants display rapid aggressive reactions upon presentation of non
      nestmate odor (120 to 160 ms); ii) ants' aggressiveness towards non-nestmates can
      be specifically reduced by exposure to non-nestmate odor only, showing that
      social interactions are not required to alter responses towards non-nestmates;
      iii) decision-making by ants does not require information transfer between brain
      hemispheres, but relies on side-specific decision rules.
      CONCLUSIONS/SIGNIFICANCE: Our results strongly suggest that first-order olfactory
      processing centers (up to the antennal lobes) are likely to play a key role in
      ant nestmate recognition. We hypothesize that the coarse level of discrimination
      achieved in the antennal lobes early in odor processing provides enough
      information to determine appropriate behavioral responses towards non-nestmates.
      This asks for a reappraisal of the mechanisms underlying social recognition in
      insects.

PMID- 20808781
TI  - IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin
      and leptin sensitivity through IKKbeta and ER stress inhibition.
AB  - Overnutrition caused by overeating is associated with insulin and leptin
      resistance through IKKbeta activation and endoplasmic reticulum (ER) stress in
      the hypothalamus. Here we show that physical exercise suppresses hyperphagia and
      associated hypothalamic IKKbeta/NF-kappaB activation by a mechanism dependent
      upon the pro-inflammatory cytokine interleukin (IL)-6. The disruption of
      hypothalamic-specific IL-6 action blocked the beneficial effects of exercise on
      the re-balance of food intake and insulin and leptin resistance. This molecular
      mechanism, mediated by physical activity, involves the anti-inflammatory protein
      IL-10, a core inhibitor of IKKbeta/NF-kappaB signaling and ER stress. We report
      that exercise and recombinant IL-6 requires IL-10 expression to suppress
      hyperphagia-related obesity. Moreover, in contrast to control mice, exercise
      failed to reverse the pharmacological activation of IKKbeta and ER stress in
      C3H/HeJ mice deficient in hypothalamic IL-6 and IL-10 signaling. Hence,
      inflammatory signaling in the hypothalamus links beneficial physiological effects
      of exercise to the central action of insulin and leptin.

PMID- 20808783
TI  - Loss of hepatocyte-nuclear-factor-1alpha impacts on adult mouse intestinal
      epithelial cell growth and cell lineages differentiation.
AB  - BACKGROUND AND AIMS: Although Hnf1alpha is crucial for pancreas and liver
      functions, it is believed to play a limited functional role for intestinal
      epithelial functions. The aim of this study was to assess the consequences of
      abrogating Hnf1alpha on the maintenance of adult small intestinal epithelial
      functions. METHODOLOGY/PRINCIPAL FINDINGS: An Hnf1alpha knockout mouse model was
      used. Assessment of histological abnormalities, crypt epithelial cell
      proliferation, epithelial barrier, glucose transport and signalling pathways were
      measured in these animals. Changes in global gene expression were also analyzed.
      Mice lacking Hnf1alpha displayed increased crypt proliferation and
      intestinalomegaly as well as a disturbance of intestinal epithelial cell lineages
      production during adult life. This phenotype was associated with a decrease of
      the mucosal barrier function and lumen-to-blood glucose delivery. The mammalian
      target of rapamycin (mTOR) signalling pathway was found to be overly activated in
      the small intestine of adult Hnf1alpha mutant mice. The intestinal epithelium of
      Hnf1alpha null mice displayed a reduction of the enteroendocrine cell population.
      An impact was also observed on proper Paneth cell differentiation with
      abnormalities in the granule exocytosis pathway. CONCLUSIONS/SIGNIFICANCE:
      Together, these results unravel a functional role for Hnf1alpha in regulating
      adult intestinal growth and sustaining the functions of intestinal epithelial
      cell lineages.

PMID- 20808784
TI  - Mechanical strain stabilizes reconstituted collagen fibrils against enzymatic
      degradation by mammalian collagenase matrix metalloproteinase 8 (MMP-8).
AB  - BACKGROUND: Collagen, a triple-helical, self-organizing protein, is the
      predominant structural protein in mammals. It is found in bone, ligament, tendon,
      cartilage, intervertebral disc, skin, blood vessel, and cornea. We have recently
      postulated that fibrillar collagens (and their complementary enzymes) comprise
      the basis of a smart structural system which appears to support the retention of
      molecules in fibrils which are under tensile mechanical strain. The theory
      suggests that the mechanisms which drive the preferential accumulation of
      collagen in loaded tissue operate at the molecular level and are not solely cell
      driven. The concept reduces control of matrix morphology to an interaction
      between molecules and the most relevant, physical, and persistent signal:
      mechanical strain. METHODOLOGY/PRINCIPAL FINDINGS: The investigation was carried
      out in an environmentally-controlled microbioreactor in which reconstituted type
      I collagen micronetworks were gently strained between micropipettes. The strained
      micronetworks were exposed to active matrix metalloproteinase 8 (MMP-8) and
      relative degradation rates for loaded and unloaded fibrils were tracked
      simultaneously using label-free differential interference contrast (DIC) imaging.
      It was found that applied tensile mechanical strain significantly increased
      degradation time of loaded fibrils compared to unloaded, paired controls. In many
      cases, strained fibrils were detectable long after unstrained fibrils were
      degraded. CONCLUSIONS/SIGNIFICANCE: In this investigation we demonstrate for the
      first time that applied mechanical strain preferentially preserves collagen
      fibrils in the presence of a physiologically-important mammalian enzyme: MMP-8.
      These results have the potential to contribute to our understanding of many
      collagen matrix phenomena including development, adaptation, remodeling and
      disease. Additionally, tissue engineering could benefit from the ability to
      sculpt desired structures from physiologically compatible and mutable collagen.

PMID- 20808785
TI  - Structural basis for certain naturally occurring bioflavonoids to function as
      reducing co-substrates of cyclooxygenase I and II.
AB  - BACKGROUND: Recent studies showed that some of the dietary bioflavonoids can
      strongly stimulate the catalytic activity of cyclooxygenase (COX) I and II in
      vitro and in vivo, presumably by facilitating enzyme re-activation. In this
      study, we sought to understand the structural basis of COX activation by these
      dietary compounds. METHODOLOGY/PRINCIPAL FINDINGS: A combination of molecular
      modeling studies, biochemical analysis and site-directed mutagenesis assay was
      used as research tools. Three-dimensional quantitative structure-activity
      relationship analysis (QSAR/CoMFA) predicted that the ability of bioflavonoids to
      activate COX I and II depends heavily on their B-ring structure, a moiety known
      to be associated with strong antioxidant ability. Using the homology modeling and
      docking approaches, we identified the peroxidase active site of COX I and II as
      the binding site for bioflavonoids. Upon binding to this site, bioflavonoid can
      directly interact with hematin of the COX enzyme and facilitate the electron
      transfer from bioflavonoid to hematin. The docking results were verified by
      biochemical analysis, which reveals that when the cyclooxygenase activity of COXs
      is inhibited by covalent modification, myricetin can still stimulate the
      conversion of PGG(2) to PGE(2), a reaction selectively catalyzed by the
      peroxidase activity. Using the site-directed mutagenesis analysis, we confirmed
      that Q189 at the peroxidase site of COX II is essential for bioflavonoids to bind
      and re-activate its catalytic activity. CONCLUSIONS/SIGNIFICANCE: These findings
      provide the structural basis for bioflavonoids to function as high-affinity
      reducing co-substrates of COXs through binding to the peroxidase active site,
      facilitating electron transfer and enzyme re-activation.

PMID- 20808786
TI  - A structure-based approach for mapping adverse drug reactions to the perturbation
      of underlying biological pathways.
AB  - Adverse drug reactions (ADR), also known as side-effects, are complex undesired
      physiologic phenomena observed secondary to the administration of
      pharmaceuticals. Several phenomena underlie the emergence of each ADR; however, a
      dominant factor is the drug's ability to modulate one or more biological
      pathways. Understanding the biological processes behind the occurrence of ADRs
      would lead to the development of safer and more effective drugs. At present, no
      method exists to discover these ADR-pathway associations. In this paper we
      introduce a computational framework for identifying a subset of these
      associations based on the assumption that drugs capable of modulating the same
      pathway may induce similar ADRs. Our model exploits multiple information
      resources. First, we utilize a publicly available dataset pairing drugs with
      their observed ADRs. Second, we identify putative protein targets for each drug
      using the protein structure database and in-silico virtual docking. Third, we
      label each protein target with its known involvement in one or more biological
      pathways. Finally, the relationships among these information sources are mined
      using multiple stages of logistic-regression while controlling for over-fitting
      and multiple-hypothesis testing. As proof-of-concept, we examined a dataset of
      506 ADRs, 730 drugs, and 830 human protein targets. Our method yielded 185 ADR
      pathway associations of which 45 were selected to undergo a manual literature
      review. We found 32 associations to be supported by the scientific literature.

PMID- 20808787
TI  - Using re-sampling methods in mortality studies.
AB  - Traditional methods of computing standardized mortality ratios (SMR) in mortality
      studies rely upon a number of conventional statistical propositions to estimate
      confidence intervals for obtained values. Those propositions include a common but
      arbitrary choice of the confidence level and the assumption that observed number
      of deaths in the test sample is a purely random quantity. The latter assumption
      may not be fully justified for a series of periodic "overlapping" studies. We
      propose a new approach to evaluating the SMR, along with its confidence interval,
      based on a simple re-sampling technique. The proposed method is most
      straightforward and requires neither the use of above assumptions nor any
      rigorous technique, employed by modern re-sampling theory, for selection of a
      sample set. Instead, we include all possible samples that correspond to the
      specified time window of the study in the re-sampling analysis. As a result,
      directly obtained confidence intervals for repeated overlapping studies may be
      tighter than those yielded by conventional methods. The proposed method is
      illustrated by evaluating mortality due to a hypothetical risk factor in a life
      insurance cohort. With this method used, the SMR values can be forecast more
      precisely than when using the traditional approach. As a result, the appropriate
      risk assessment would have smaller uncertainties.

PMID- 20808788
TI  - Complex exon-intron marking by histone modifications is not determined solely by
      nucleosome distribution.
AB  - It has recently been shown that nucleosome distribution, histone modifications
      and RNA polymerase II (Pol II) occupancy show preferential association with exons
      ("exon-intron marking"), linking chromatin structure and function to co
      transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing
      studies suggested that these marking patterns reflect the nucleosomal landscape.
      By analyzing ChIP-chip datasets across the human genome in three cell types, we
      have found that this marking system is far more complex than previously observed.
      We show here that a range of histone modifications and Pol II are preferentially
      associated with exons. However, there is noticeable cell-type specificity in the
      degree of exon marking by histone modifications and, surprisingly, this is also
      reflected in some histone modifications patterns showing biases towards introns.
      Exon-intron marking is laid down in the absence of transcription on silent genes,
      with some marking biases changing or becoming reversed for genes expressed at
      different levels. Furthermore, the relationship of this marking system with
      splicing is not simple, with only some histone modifications reflecting exon
      usage/inclusion, while others mirror patterns of exon exclusion. By examining
      nucleosomal distributions in all three cell types, we demonstrate that these
      histone modification patterns cannot solely be accounted for by differences in
      nucleosome levels between exons and introns. In addition, because of inherent
      differences between ChIP-chip array and ChIP-sequencing approaches, these
      platforms report different nucleosome distribution patterns across the human
      genome. Our findings confound existing views and point to active cellular
      mechanisms which dynamically regulate histone modification levels and account for
      exon-intron marking. We believe that these histone modification patterns provide
      links between chromatin accessibility, Pol II movement and co-transcriptional
      splicing.

PMID- 20808789
TI  - Soft matrices suppress cooperative behaviors among receptor-ligand bonds in cell
      adhesion.
AB  - The fact that biological tissues are stable over prolonged periods of time while
      individual receptor-ligand bonds only have limited lifetime underscores the
      critical importance of cooperative behaviors of multiple molecular bonds, in
      particular the competition between the rate of rupture of closed bonds (death
      rate) and the rate of rebinding of open bonds (birth rate) in a bond cluster. We
      have recently shown that soft matrices can greatly increase the death rate in a
      bond cluster by inducing severe stress concentration near the adhesion edges. In
      the present paper, we report a more striking effect that, irrespective of stress
      concentration, soft matrices also suppress the birth rate in a bond cluster by
      increasing the local separation distance between open bonds. This is shown by
      theoretical analysis as well as Monte Carlo simulations based on a stochastic
      elasticity model in which stochastic descriptions of molecular bonds and elastic
      descriptions of interfacial force/separation are unified in a single modeling
      framework. Our findings not only are important for understanding the role of
      elastic matrices in cell adhesion, but also have general implications on adhesion
      between soft materials.

PMID- 20808790
TI  - Cyclin B1/Cdk1 phosphorylation of mitochondrial p53 induces anti-apoptotic
      response.
AB  - The pro-apoptotic function of p53 has been well defined in preventing genomic
      instability and cell transformation. However, the intriguing fact that p53
      contributes to a pro-survival advantage of tumor cells under DNA damage
      conditions raises a critical question in radiation therapy for the 50% human
      cancers with intact p53 function. Herein, we reveal an anti-apoptotic role of
      mitochondrial p53 regulated by the cell cycle complex cyclin B1/Cdk1 in
      irradiated human colon cancer HCT116 cells with p53(+/+) status. Steady-state
      levels of p53 and cyclin B1/Cdk1 were identified in the mitochondria of many
      human and mouse cells, and their mitochondrial influx was significantly enhanced
      by radiation. The mitochondrial kinase activity of cyclin B1/Cdk1 was found to
      specifically phosphorylate p53 at Ser-315 residue, leading to enhanced
      mitochondrial ATP production and reduced mitochondrial apoptosis. The improved
      mitochondrial function can be blocked by transfection of mutant p53 Ser-315-Ala,
      or by siRNA knockdown of cyclin B1 and Cdk1 genes. Enforced translocation of
      cyclin B1 and Cdk1 into mitochondria with a mitochondrial-targeting-peptide
      increased levels of Ser-315 phosphorylation on mitochondrial p53, improved ATP
      production and decreased apoptosis by sequestering p53 from binding to Bcl-2 and
      Bcl-xL. Furthermore, reconstitution of wild-type p53 in p53-deficient HCT116 p53(
      /-) cells resulted in an increased mitochondrial ATP production and suppression
      of apoptosis. Such phenomena were absent in the p53-deficient HCT116 p53(-/-)
      cells reconstituted with the mutant p53. These results demonstrate a unique anti
      apoptotic function of mitochondrial p53 regulated by cyclin B1/Cdk1-mediated Ser
      315 phosphorylation in p53-wild-type tumor cells, which may provide insights for
      improving the efficacy of anti-cancer therapy, especially for tumors that retain
      p53.

PMID- 20808791
TI  - Structure activity relationship of dendrimer microbicides with dual action
      antiviral activity.
AB  - BACKGROUND: Topical microbicides, used by women to prevent the transmission of
      HIV and other sexually transmitted infections are urgently required. Dendrimers
      are highly branched nanoparticles being developed as microbicides. However, the
      anti-HIV and HSV structure-activity relationship of dendrimers comprising
      benzyhydryl amide cores and lysine branches, and a comprehensive analysis of
      their broad-spectrum anti-HIV activity and mechanism of action have not been
      published. METHODS AND FINDINGS: Dendrimers with optimized activity against HIV-1
      and HSV-2 were identified with respect to the number of lysine branches
      (generations) and surface groups. Antiviral activity was determined in cell
      culture assays. Time-of-addition assays were performed to determine dendrimer
      mechanism of action. In vivo toxicity and HSV-2 inhibitory activity were
      evaluated in the mouse HSV-2 susceptibility model. Surface groups imparting the
      most potent inhibitory activity against HIV-1 and HSV-2 were naphthalene
      disulfonic acid (DNAA) and 3,5-disulfobenzoic acid exhibiting the greatest
      anionic charge and hydrophobicity of the seven surface groups tested. Their anti
      HIV-1 activity did not appreciably increase beyond a second-generation dendrimer
      while dendrimers larger than two generations were required for potent anti-HSV-2
      activity. Second (SPL7115) and fourth generation (SPL7013) DNAA dendrimers
      demonstrated broad-spectrum anti-HIV activity. However, SPL7013 was more active
      against HSV and blocking HIV-1 envelope mediated cell-to-cell fusion. SPL7013 and
      SPL7115 inhibited viral entry with similar potency against CXCR4-(X4) and CCR5
      using (R5) HIV-1 strains. SPL7013 was not toxic and provided at least 12 h
      protection against HSV-2 in the mouse vagina. CONCLUSIONS: Dendrimers can be
      engineered with optimized potency against HIV and HSV representing a unique
      platform for the controlled synthesis of chemically defined multivalent agents as
      viral entry inhibitors. SPL7013 is formulated as VivaGel(R) and is currently in
      clinical development to provide protection against HIV and HSV. SPL7013 could
      also be combined with other microbicides.

PMID- 20808792
TI  - Leftward lateralization of auditory cortex underlies holistic sound perception in
      Williams syndrome.
AB  - BACKGROUND: Individuals with the rare genetic disorder Williams-Beuren syndrome
      (WS) are known for their characteristic auditory phenotype including strong
      affinity to music and sounds. In this work we attempted to pinpoint a neural
      substrate for the characteristic musicality in WS individuals by studying the
      structure-function relationship of their auditory cortex. Since WS subjects had
      only minor musical training due to psychomotor constraints we hypothesized that
      any changes compared to the control group would reflect the contribution of
      genetic factors to auditory processing and musicality. METHODOLOGY/PRINCIPAL
      FINDINGS: Using psychoacoustics, magnetoencephalography and magnetic resonance
      imaging, we show that WS individuals exhibit extreme and almost exclusive
      holistic sound perception, which stands in marked contrast to the even
      distribution of this trait in the general population. Functionally, this was
      reflected by increased amplitudes of left auditory evoked fields. On the
      structural level, volume of the left auditory cortex was 2.2-fold increased in WS
      subjects as compared to control subjects. Equivalent volumes of the auditory
      cortex have been previously reported for professional musicians.
      CONCLUSIONS/SIGNIFICANCE: There has been an ongoing debate in the neuroscience
      community as to whether increased gray matter of the auditory cortex in musicians
      is attributable to the amount of training or innate disposition. In this study
      musical education of WS subjects was negligible and control subjects were
      carefully matched for this parameter. Therefore our results not only unravel the
      neural substrate for this particular auditory phenotype, but in addition propose
      WS as a unique genetic model for training-independent auditory system properties.

PMID- 20808793
TI  - Are cytochrome P450 CYP2C8 and CYP2C9 polymorphisms associated with ibuprofen
      response in very preterm infants?
AB  - BACKGROUND: Patent ductus arteriosus (PDA) in extremely preterm infants remains a
      challenging condition with conflicting treatment strategies. Ibuprofen is
      currently used to treat PDA with ductal closure failure rate up to 40%. We test
      the hypothesis that cytochrome P450 CYP2C8/2C9 polymorphisms may predict
      ibuprofen response. METHODOLOGY/PRINCIPAL FINDINGS: We studied extremely preterm
      neonates with haemodynamically significant PDA and treated with ibuprofen. One or
      two variant CYP2C8 and/or 2C9 alleles were found in 17% of the population, most
      of them were from Caucasian ethnicity (67-74%). Response to ibuprofen and
      clinical course of infants carrying variants CYP2C8 and CYP2C9 were similar.
      Comparing infants with wild type or variant CYP2C8 and CYP2C9 genotypes, response
      rate to ibuprofen was significantly higher in wild type than in mutated carriers
      in univariate analysis (73% versus 52%, p = 0.04). Comparing responders (ductus
      closure; n = 75) and non-responders (surgical ligation; n = 36), the only two
      factors significantly associated with the response to ibuprofen using
      multivariate analysis were higher gestational age and non Caucasian ethnicity but
      not CYP2C polymorphism. CONCLUSIONS: CYP2C polymorphism was not associated with
      PDA response to ibuprofen and this factor appears not appropriate to optimize the
      ductal closure rate by modulating ibuprofen dosing strategy. This study points
      out the role for ethnicity in the interindividual variability of response to
      ibuprofen in extremely preterm infants.

PMID- 20808794
TI  - Do randomized controlled trials discuss healthcare costs?
AB  - BACKGROUND: Healthcare costs, particularly pharmaceutical costs, are a dominant
      issue for most healthcare organizations, but it is unclear if randomized
      controlled trials (RCTs) routinely discuss costs. Our objective was to assess the
      frequency and factors associated with the inclusion of costs in RCTs. METHODS AND
      FINDINGS: We randomly sampled 188 RCTs spanning three years (2003-2005) from six
      high impact journals. The sample size for RCTs was based on a calculation to
      estimate the inclusion of actual drug costs with a precision of +/-3%. Two
      reviewers independently extracted cost data and study characteristics.
      Frequencies were calculated and potential characteristics associated with the
      inclusion of costs were explored. Actual drug costs were included in 4.7% (9/188)
      of RCTs; any actual costs were included in 7.4% (14/188) of RCTs; and any mention
      of costs was included in 27.7% (52/188) of RCTs. As the amount of industry
      funding increased across RCTs, from non-profit to mixed to fully industry funded
      RCTs, there was a statistically significant reduction in the number of RCTs with
      any actual costs (Cochran-Armitage test, p = 0.005) and any mention of costs
      (Cochran-Armitage test, p = 0.02). Logistic regression analysis also indicated
      funding was associated with the inclusion of any actual cost (OR = 0.34, p =
      0.009) or any mention of costs (OR = 0.63, p = 0.02). Journal, study conclusions,
      study location, primary author's country and product age were not associated with
      inclusion of cost information. CONCLUSION: While physicians are encouraged to
      consider costs when prescribing drugs for their patients, actual drug costs were
      provided in only 5% of RCTs and were not mentioned at all in 72% of RCTs.
      Industry funded trials were less likely to include cost information. No other
      factors were associated with the inclusion of cost information.

PMID- 20808795
TI  - Competing activities of heterotrimeric G proteins in Drosophila wing maturation.
AB  - Drosophila genome encodes six alpha-subunits of heterotrimeric G proteins. The
      Galphas alpha-subunit is involved in the post-eclosion wing maturation, which
      consists of the epithelial-mesenchymal transition and cell death, accompanied by
      unfolding of the pupal wing into the firm adult flight organ. Here we show that
      another alpha-subunit Galphao can specifically antagonize the Galphas activities
      by competing for the Gbeta13F/Ggamma1 subunits of the heterotrimeric Gs protein
      complex. Loss of Gbeta13F, Ggamma1, or Galphas, but not any other G protein
      subunit, results in prevention of post-eclosion cell death and failure of the
      wing expansion. However, cell death prevention alone is not sufficient to induce
      the expansion defect, suggesting that the failure of epithelial-mesenchymal
      transition is key to the folded wing phenotypes. Overactivation of Galphas with
      cholera toxin mimics expression of constitutively activated Galphas and promotes
      wing blistering due to precocious cell death. In contrast, co-overexpression of
      Gbeta13F and Ggamma1 does not produce wing blistering, revealing the passive role
      of the Gbetagamma in the Galphas-mediated activation of apoptosis, but hinting at
      the possible function of Gbetagamma in the epithelial-mesenchymal transition. Our
      results provide a comprehensive functional analysis of the heterotrimeric G
      protein proteome in the late stages of Drosophila wing development.

PMID- 20808796
TI  - Identification of a polycystin-1 cleavage product, P100, that regulates store
      operated Ca entry through interactions with STIM1.
AB  - Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder
      resulting in large kidney cysts and eventual kidney failure. Mutations in either
      the PKD1 or PKD2/TRPP2 genes and their respective protein products, polycystin-1
      (PC1) and polycystin-2 (PC2) result in ADPKD. PC2 is known to function as a non
      selective cation channel, but PC1's function and the function of PC1 cleavage
      products are not well understood. Here we identify an endogenous PC1 cleavage
      product, P100, a 100 kDa fragment found in both wild type and epitope tagged PKD1
      knock-in mice. Expression of full length human PC1 (FL PC1) and the resulting
      P100 and C-Terminal Fragment (CTF) cleavage products in both MDCK and CHO cells
      significantly reduces the store operated Ca(2+) entry (SOCE) resulting from
      thapsigargin induced store depletion. Exploration into the roles of P100 and CTF
      in SOCE inhibition reveal that P100, when expressed in Xenopus laevis oocytes,
      directly inhibits the SOCE currents but CTF does not, nor does P100 when
      containing the disease causing R4227X mutation. Interestingly, we also found that
      in PC1 expressing MDCK cells, translocation of the ER Ca(2+) sensor protein STIM1
      to the cell periphery was significantly altered. In addition, P100 Co
      immunoprecipitates with STIM1 but CTF does not. The expression of P100 in CHO
      cells recapitulates the STIM1 translocation inhibition seen with FL PC1. These
      data describe a novel polycystin-1 cleavage product, P100, which functions to
      reduce SOCE via direct inhibition of STIM1 translocation; a function with
      consequences for ADPKD.

PMID- 20808797
TI  - Oral N-acetyl-cysteine attenuates loss of dopaminergic terminals in alpha
      synuclein overexpressing mice.
AB  - Levels of glutathione are lower in the substantia nigra (SN) early in Parkinson's
      disease (PD) and this may contribute to mitochondrial dysfunction and oxidative
      stress. Oxidative stress may increase the accumulation of toxic forms of alpha
      synuclein (SNCA). We hypothesized that supplementation with n-acetylcysteine
      (NAC), a source of cysteine--the limiting amino acid in glutathione synthesis,
      would protect against alpha-synuclein toxicity. Transgenic mice overexpressing
      wild-type human alpha-synuclein drank water supplemented with NAC or control
      water supplemented with alanine from ages 6 weeks to 1 year. NAC increased SN
      levels of glutathione within 5-7 weeks of treatment; however, this increase was
      not sustained at 1 year. Despite the transient nature of the impact of NAC on
      brain glutathione, the loss of dopaminergic terminals at 1 year associated with
      SNCA overexpression was significantly attenuated by NAC supplementation, as
      measured by immunoreactivity for tyrosine hydroxylase in the striatum (p = 0.007;
      unpaired, two-tailed t-test), with a similar but nonsignificant trend for
      dopamine transporter (DAT) immunoreactivity. NAC significantly decreased the
      levels of human SNCA in the brains of PDGFb-SNCA transgenic mice compared to
      alanine treated transgenics. This was associated with a decrease in nuclear
      NFkappaB localization and an increase in cytoplasmic localization of NFkappaB in
      the NAC-treated transgenics. Overall, these results indicate that oral NAC
      supplementation decreases SNCA levels in brain and partially protects against
      loss of dopaminergic terminals associated with overexpression of alpha-synuclein
      in this model.

PMID- 20808798
TI  - DLA class II alleles are associated with risk for canine symmetrical lupoid
      onychodystrophy [corrected](SLO).
AB  - Symmetrical lupoid onychodystrophy (SLO) is an immune-mediated disease in dogs
      affecting the claws with a suggested autoimmune aethiology. Sequence-based
      genotyping of the polymorphic exon 2 from DLA-DRB1, -DQA1, and -DQB1 class II
      loci were performed in a total of 98 SLO Gordon setter cases and 98 healthy
      controls. A risk haplotype (DRB1*01801/DQA1*00101/DQB1*00802) was present in 53%
      of cases and 34% of controls and conferred an elevated risk of developing SLO
      with an odds ratio (OR) of 2.1. When dogs homozygous for the risk haplotype were
      compared to all dogs not carrying the haplotype the OR was 5.4. However, a
      stronger protective haplotype (DRB1*02001/DQA1*00401/DQB1*01303, OR = 0.03, 1/OR
      = 33) was present in 16.8% of controls, but only in a single case (0.5%). The
      effect of the protective haplotype was clearly stronger than the risk haplotype,
      since 11.2% of the controls were heterozygous for the risk and protective
      haplotypes, whereas this combination was absent from cases. When the dogs with
      the protective haplotype were excluded, an OR of 2.5 was obtained when dogs
      homozygous for the risk haplotype were compared to those heterozygous for the
      risk haplotype, suggesting a co-dominant effect of the risk haplotype. In smaller
      sample sizes of the bearded collie and giant schnauzer breeds we found the same
      or similar haplotypes, sharing the same DQA1 allele, over-represented among the
      cases suggesting that the risk is associated primarily with DLA-DQ. We obtained
      conclusive results that DLA class II is significantly associated with risk of
      developing SLO in Gordon setters, thus supporting that SLO is an immune-mediated
      disease. Further studies of SLO in dogs may provide important insight into immune
      privilege of the nail apparatus and also knowledge about a number of inflammatory
      disorders of the nail apparatus like lichen planus, psoriasis, alopecia areata
      and onycholysis.

PMID- 20808799
TI  - Distinct changes in cAMP and extracellular signal-regulated protein kinase
      signalling in L-DOPA-induced dyskinesia.
AB  - BACKGROUND: In rodents, the development of dyskinesia produced by L-DOPA in the
      dopamine-depleted striatum occurs in response to increased dopamine D1 receptor
      mediated activation of the cAMP - protein kinase A and of the Ras-extracellular
      signal-regulated kinase (ERK) signalling pathways. However, very little is known,
      in non-human primates, about the regulation of these signalling cascades and
      their association with the induction, manifestation and/or maintenance of
      dyskinesia. METHODOLOGY/RESULTS: We here studied, in the gold-standard non-human
      primate model of Parkinson's disease, the changes in PKA-dependent
      phosphorylation of DARPP-32 and GluR1 AMPA receptor, as well as in ERK and
      ribosomal protein S6 (S6) phosphorylation, associated to acute and chronic
      administration of L-DOPA. Increased phosphorylation of DARPP-32 and GluR1 was
      observed in both L-DOPA first-ever exposed and chronically-treated dyskinetic
      parkinsonian monkeys. In contrast, phosphorylation of ERK and S6 was enhanced
      preferentially after acute L-DOPA administration and decreased during the course
      of chronic treatment. CONCLUSION: Dysregulation of cAMP signalling is maintained
      during the course of chronic L-DOPA administration, while abnormal ERK signalling
      peaks during the initial phase of L-DOPA treatment and decreases following
      prolonged exposure. While cAMP signalling enhancement is associated with
      dyskinesia, abnormal ERK signalling is associated with priming.

PMID- 20808800
TI  - Optimizing combination therapies with existing and future CML drugs.
AB  - Small-molecule inhibitors imatinib, dasatinib and nilotinib have been developed
      to treat Chromic Myeloid Leukemia (CML). The existence of a triple-cross
      resistant mutation, T315I, has been a challenging problem, which can be overcome
      by finding new inhibitors. Many new compounds active against T315I mutants are
      now at different stages of development. In this paper we develop an algorithm
      which can weigh different combination treatment protocols according to their
      cross-resistance properties, and find the protocols with the highest probability
      of treatment success. This algorithm also takes into account drug toxicity by
      minimizing the number of drugs used, and their concentration. Although our
      methodology is based on a stochastic model of CML microevolution, the algorithm
      itself does not require measurements of any parameters (such as mutation rates,
      or division/death rates of cells), and can be used by medical professionals
      without a mathematical background. For illustration, we apply this algorithm to
      the mutation data obtained in [1], [2].

PMID- 20808801
TI  - Identification of methylated genes associated with aggressive bladder cancer.
AB  - Approximately 500,000 individuals diagnosed with bladder cancer in the U.S.
      require routine cystoscopic follow-up to monitor for disease recurrences or
      progression, resulting in over $2 billion in annual expenditures. Identification
      of new diagnostic and monitoring strategies are clearly needed, and markers
      related to DNA methylation alterations hold great promise due to their stability,
      objective measurement, and known associations with the disease and with its
      clinical features. To identify novel epigenetic markers of aggressive bladder
      cancer, we utilized a high-throughput DNA methylation bead-array in two distinct
      population-based series of incident bladder cancer (n = 73 and n = 264,
      respectively). We then validated the association between methylation of these
      candidate loci with tumor grade in a third population (n = 245) through bisulfite
      pyrosequencing of candidate loci. Array based analyses identified 5 loci for
      further confirmation with bisulfite pyrosequencing. We identified and confirmed
      that increased promoter methylation of HOXB2 is significantly and independently
      associated with invasive bladder cancer and methylation of HOXB2, KRT13 and FRZB
      together significantly predict high-grade non-invasive disease. Methylation of
      these genes may be useful as clinical markers of the disease and may point to
      genes and pathways worthy of additional examination as novel targets for
      therapeutic treatment.

PMID- 20808802
TI  - Different effects of angiotensin II and angiotensin-(1-7) on vascular smooth
      muscle cell proliferation and migration.
AB  - BACKGROUND: Angiotensin (Ang) II and Ang-(1-7) are two of the bioactive peptides
      of the rennin-angiotensin system. Ang II is involved in the development of
      cardiovascular disease, such as hypertension and atherosclerosis, while Ang-(1-7)
      shows cardiovascular protection in contrast to Ang II. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, we investigated effects of Ang II and Ang-(1-7) on
      vascular smooth muscle cell (SMC) proliferation and migration, which are critical
      in the formation of atherosclerotic lesions. Treatment with Ang II resulted in an
      increase of SMC proliferation, whereas Ang-(1-7) alone had no effects. However,
      preincubation with Ang-(1-7) inhibited Ang II-induced SMC proliferation. Ang II
      promoted SMC migration, and this effect was abolished by pretreatment with Ang-(1
      7). The stimulatory effects of Ang II on SMC proliferation and migration were
      blocked by the Ang II receptor antagonist lorsartan, while the inhibitory effects
      of Ang-(1-7) were abolished by the Ang-(1-7) receptor antagonist A-799. Ang II
      treatment caused activation of ERK1/2 mediated signaling, and this was inhibited
      by preincubation of SMCs with Ang-(1-7). CONCLUSION: These results suggest that
      Ang-(1-7) inhibits Ang II-induced SMC proliferation and migration, at least in
      part, through negative modulation of Ang II induced ERK1/2 activity.

PMID- 20808803
TI  - The mechanism of release of P-TEFb and HEXIM1 from the 7SK snRNP by viral and
      cellular activators includes a conformational change in 7SK.
AB  - BACKGROUND: The positive transcription elongation factor, P-TEFb, is required for
      the production of mRNAs, however the majority of the factor is present in the 7SK
      snRNP where it is inactivated by HEXIM1. Expression of HIV-1 Tat leads to release
      of P-TEFb and HEXIM1 from the 7SK snRNP in vivo, but the release mechanisms are
      unclear. METHODOLOGY/PRINCIPAL FINDINGS: We developed an in vitro P-TEFb release
      assay in which the 7SK snRNP immunoprecipitated from HeLa cell lysates using
      antibodies to LARP7 was incubated with potential release factors. We found that P
      TEFb was directly released from the 7SK snRNP by HIV-1 Tat or the P-TEFb binding
      region of the cellular activator Brd4. Glycerol gradient sedimentation analysis
      was used to demonstrate that the same Brd4 protein transfected into HeLa cells
      caused the release of P-TEFb and HEXIM1 from the 7SK snRNP in vivo. Although
      HEXIM1 binds tightly to 7SK RNA in vitro, release of P-TEFb from the 7SK snRNP is
      accompanied by the loss of HEXIM1. Using a chemical modification method, we
      determined that concomitant with the release of HEXIM1, 7SK underwent a major
      conformational change that blocks re-association of HEXIM1.
      CONCLUSIONS/SIGNIFICANCE: Given that promoter proximally paused polymerases are
      present on most human genes, understanding how activators recruit P-TEFb to those
      genes is critical. Our findings reveal that the two tested activators can extract
      P-TEFb from the 7SK snRNP. Importantly, we found that after P-TEFb is extracted a
      dramatic conformational change occurred in 7SK concomitant with the ejection of
      HEXIM1. Based on our findings, we hypothesize that reincorporation of HEXIM1 into
      the 7SK snRNP is likely the regulated step of reassembly of the 7SK snRNP
      containing P-TEFb.

PMID- 20808804
TI  - Deletion of Nhlh2 results in a defective torpor response and reduced Beta
      adrenergic receptor expression in adipose tissue.
AB  - BACKGROUND: Mice with a targeted deletion of the basic helix-loop-helix
      transcription factor, Nescient Helix-Loop-Helix 2 (Nhlh2), display adult-onset
      obesity with significant increases in their fat depots, abnormal responses to
      cold exposure, and reduced spontaneous physical activity levels. These
      phenotypes, accompanied by the hypothalamic expression of Nhlh2, make the Nhlh2
      knockout (N2KO) mouse a useful model to study the role of central nervous system
      (CNS) control on peripheral tissue such as adipose tissue. METHODOLOGY:
      Differences in body temperature and serum analysis of leptin were performed in
      fasted and ad lib fed wild-type (WT) and N2KO mice. Histological analysis of
      white (WAT) and brown adipose tissue (BAT) was performed. Gene and protein level
      expression of inflammatory and metabolic markers were compared between the two
      genotypes. PRINCIPAL FINDINGS: We report significant differences in serum leptin
      levels and body temperature in N2KO mice compared with WT mice exposed to a 24
      hour fast, suggestive of a defect in both white (WAT) and brown adipose tissue
      (BAT) function. As compared to WT mice, N2KO mice showed increased serum IL-6
      protein and WAT IL-6 mRNA levels. This was accompanied by slight elevations of
      mRNA for several macrophage markers, including expression of macrophage specific
      protein F4/80 in adipose, suggestive of macrophage infiltration of WAT in the
      mutant animals. The mRNAs for beta3-adrenergic receptors (beta3-AR), beta2-AR and
      uncoupling proteins were significantly reduced in WAT and BAT from N2KO mice
      compared with WT mice. CONCLUSIONS: These studies implicate Nhlh2 in the central
      control of WAT and BAT function, with lack of Nhlh2 leading to adipose
      inflammation and altered gene expression, impaired leptin response to fasting,
      all suggestive of a deficient torpor response in mutant animals.

PMID- 20808805
TI  - Paeonol oxime inhibits bFGF-induced angiogenesis and reduces VEGF levels in
      fibrosarcoma cells.
AB  - BACKGROUND: We previously reported the anti-angiogenic activity of paeonol
      isolated from Moutan Cortex. In the present study, we investigated the negative
      effect of paeonol oxime (PO, a paeonol derivative) on basic fibroblast growth
      factor (bFGF)-mediated angiogenesis in human umbilical vein endothelial cells
      (HUVECs) (including tumor angiogenesis) and pro-survival activity in HT-1080
      fibrosarcoma cell line. METHODOLOGY/PRINCIPAL FINDINGS: We showed that PO (IC(50)
      = 17.3 microg/ml) significantly inhibited bFGF-induced cell proliferation, which
      was achieved with higher concentrations of paeonol (IC(50) over 200 microg). The
      treatment with PO blocked bFGF-stimulated migration and in vitro capillary
      differentiation (tube formation) in a dose-dependent manner. Furthermore, PO was
      able to disrupt neovascularization in vivo. Interestingly, PO (25 microg/ml)
      decreased the cell viability of HT-1080 fibrosarcoma cells but not that of
      HUVECs. The treatment with PO at 12.5 microg/ml reduced the levels of
      phosphorylated AKT and VEGF expression (intracellular and extracelluar) in HT
      1080 cells. Consistently, immunefluorescence imaging analysis revealed that PO
      treatment attenuated AKT phosphorylation in HT-1080 cells.
      CONCLUSIONS/SIGNIFICANCE: Taken together, these results suggest that PO inhibits
      bFGF-induced angiogenesis in HUVECs and decreased the levels of PI3K, phospho-AKT
      and VEGF in HT-1080 cells.

PMID- 20808806
TI  - The effects of tertiary and quaternary infections on the epidemiology of dengue.
AB  - The epidemiology of dengue is characterised by irregular epidemic outbreaks and
      desynchronised dynamics of its four co-circulating virus serotypes. Whilst
      infection by one serotype appears to convey life-long protection to homologous
      infection, it is believed to be a risk factor for severe disease manifestations
      upon secondary, heterologous infection due to the phenomenon of Antibody
      Dependent Enhancement (ADE). Subsequent clinical infections are rarely reported
      and, since the majority of dengue infections are generally asymptomatic, it is
      not clear if and to what degree tertiary or quaternary infections contribute to
      dengue epidemiology. Here we investigate the effect of third and subsequent
      infections on the transmission dynamics of dengue and show that although the
      qualitative patterns are largely equivalent, the system more readily exhibits the
      desynchronised serotype oscillations and multi-annual epidemic outbreaks upon
      their inclusion. More importantly, permitting third and fourth infections
      significantly increases the force of infection without resorting to high basic
      reproductive numbers. Realistic age-prevalent patterns and seroconversion rates
      are therefore easier reconciled with a low value of dengue's transmission
      potential if allowing for more than two infections; this should have important
      consequences for dengue control and intervention measures.

PMID- 20808807
TI  - Growth performance and root transcriptome remodeling of Arabidopsis in response
      to Mars-like levels of magnesium sulfate.
AB  - BACKGROUND: Martian regolith (unconsolidated surface material) is a potential
      medium for plant growth in bioregenerative life support systems during manned
      missions on Mars. However, hydrated magnesium sulfate mineral levels in the
      regolith of Mars can reach as high as 10 wt%, and would be expected to be highly
      inhibitory to plant growth. METHODOLOGY AND PRINCIPAL FINDINGS: Disabling ion
      transporters AtMRS2-10 and AtSULTR1;2, which are plasma membrane localized in
      peripheral root cells, is not an effective way to confer tolerance to magnesium
      sulfate soils. Arabidopsis mrs2-10 and sel1-10 knockout lines do not mitigate the
      growth inhibiting impacts of high MgSO(4).7H(2)O concentrations observed with
      wildtype plants. A global approach was used to identify novel genes with
      potential to enhance tolerance to high MgSO(4).7H(2)O (magnesium sulfate) stress.
      The early Arabidopsis root transcriptome response to elevated concentrations of
      magnesium sulfate was characterized in Col-0, and also between Col-0 and the
      mutant line cax1-1, which was confirmed to be relatively tolerant of high levels
      of MgSO(4).7H(2)O in soil solution. Differentially expressed genes in Col-0
      treated for 45 min. encode enzymes primarily involved in hormone metabolism,
      transcription factors, calcium-binding proteins, kinases, cell wall related
      proteins and membrane-based transporters. Over 200 genes encoding transporters
      were differentially expressed in Col-0 up to 180 min. of exposure, and one of the
      first down-regulated genes was CAX1. The importance of this early response in
      wildtype Arabidopsis is exemplified in the fact that only four transcripts were
      differentially expressed between Col-0 and cax1-1 at 180 min. after initiation of
      treatment. CONCLUSIONS/SIGNIFICANCE: The results provide a solid basis for the
      understanding of the metabolic response of plants to elevated magnesium sulfate
      soils; it is the first transcriptome analysis of plants in this environment. The
      results foster the development of Mars soil-compatible plants by showing that
      cax1 mutants exhibit partial tolerance to magnesium sulfate, and by elucidating a
      small subset (500 vs. >10,000) of candidate genes for mutation or metabolic
      engineering that will enhance tolerance to magnesium sulfate soils.

PMID- 20808808
TI  - Mast cell survival and mediator secretion in response to hypoxia.
AB  - Tissue hypoxia is a consequence of decreased oxygen levels in different
      inflammatory conditions, many associated with mast cell activation. However, the
      effect of hypoxia on mast cell functions is not well established. Here, we have
      investigated the effect of hypoxia per se on human mast cell survival, mediator
      secretion, and reactivity. Human cord blood derived mast cells were subjected to
      three different culturing conditions: culture and stimulation in normoxia (21%
      O(2)); culture and stimulation in hypoxia (1% O(2)); or 24 hour culture in
      hypoxia followed by stimulation in normoxia. Hypoxia, per se, did not induce mast
      cell degranulation, but we observed an increased secretion of IL-6, where
      autocrine produced IL-6 promoted mast cell survival. Hypoxia did not have any
      effect on A23187 induced degranulation or secretion of cytokines. In contrast,
      cytokine secretion after LPS or CD30 treatment was attenuated, but not inhibited,
      in hypoxia compared to normoxia. Our data suggests that mast cell survival,
      degranulation and cytokine release are sustained under hypoxia. This may be of
      importance for host defence where mast cells in a hypoxic tissue can react to
      intruders, but also in chronic inflammations where mast cell reactivity is not
      inhibited by the inflammatory associated hypoxia.

PMID- 20808810
TI  - Presaging critical residues in protein interfaces-web server (PCRPi-W): a web
      server to chart hot spots in protein interfaces.
AB  - BACKGROUND: It is well established that only a portion of residues that mediate
      protein-protein interactions (PPIs), the so-called hot spot, contributes the most
      to the total binding energy, and thus its identification is an important and
      relevant question that has clear applications in drug discovery and protein
      design. The experimental identification of hot spots is however a lengthy and
      costly process, and thus there is an interest in computational tools that can
      complement and guide experimental efforts. PRINCIPAL FINDINGS: Here, we present
      Presaging Critical Residues in Protein interfaces-Web server
      (http://www.bioinsilico.org/PCRPi), a web server that implements a recently
      described and highly accurate computational tool designed to predict critical
      residues in protein interfaces: PCRPi. PRCPi depends on the integration of
      structural, energetic, and evolutionary-based measures by using Bayesian Networks
      (BNs). CONCLUSIONS: PCRPi-W has been designed to provide an easy and convenient
      access to the broad scientific community. Predictions are readily available for
      download or presented in a web page that includes among other information links
      to relevant files, sequence information, and a Jmol applet to visualize and
      analyze the predictions in the context of the protein structure.

PMID- 20808809
TI  - Glycosaminoglycan sulphation affects the seeded misfolding of a mutant prion
      protein.
AB  - BACKGROUND: The accumulation of protease resistant conformers of the prion
      protein (PrP(res)) is a key pathological feature of prion diseases. Polyanions,
      including RNA and glycosaminoglycans have been identified as factors that
      contribute to the propagation, transmission and pathogenesis of prion disease.
      Recent studies have suggested that the contribution of these cofactors to prion
      propagation may be species specific. METHODOLOGY/PRINCIPAL FINDING: In this study
      a cell-free assay was used to investigate the molecular basis of polyanion
      stimulated PrP(res) formation using brain tissue or cell line derived murine PrP.
      Enzymatic depletion of endogenous nucleic acids or heparan sulphate (HS) from the
      PrP(C) substrate was found to specifically prevent PrP(res) formation seeded by
      mouse derived PrP(Sc). Modification of the negative charge afforded by the
      sulphation of glycosaminoglycans increased the ability of a familial PrP mutant
      to act as a substrate for PrP(res) formation, while having no effect on PrP(res)
      formed by wildtype PrP. This difference may be due to the observed differences in
      the binding of wild type and mutant PrP for glycosaminoglycans.
      CONCLUSIONS/SIGNIFICANCE: Cofactor requirements for PrP(res) formation are host
      species and prion strain specific and affected by disease associated mutations of
      the prion protein. This may explain both species and strain dependent propagation
      characteristics and provide insights into the underlying mechanisms of familial
      prion disease. It further highlights the challenge of designing effective
      therapeutics against a disease which effects a range of mammalian species, caused
      by range of aetiologies and prion strains.

PMID- 20808811
TI  - Lymphocytes accelerate epithelial tight junction assembly: role of AMP-activated
      protein kinase (AMPK).
AB  - The tight junctions (TJs), characteristically located at the apicolateral borders
      of adjacent epithelial cells, are required for the proper formation of epithelial
      cell polarity as well as for sustaining the mucosal barrier to the external
      environment. The observation that lymphocytes are recruited by epithelial cells
      to the sites of infection [1] suggests that they may play a role in the
      modulation of epithelial barrier function and thus contribute to host defense. To
      test the ability of lymphocytes to modulate tight junction assembly in epithelial
      cells, we set up a lymphocyte-epithelial cell co-culture system, in which Madin
      Darby canine kidney (MDCK) cells, a well-established model cell line for studying
      epithelial TJ assembly [2], were co-cultured with mouse lymphocytes to mimic an
      infection state. In a typical calcium switch experiment, the TJ assembly in co
      culture was found to be accelerated compared to that in MDCK cells alone. This
      accelaration was found to be mediated by AMP-activated protein kinase (AMPK).
      AMPK activation was independent of changes in cellular ATP levels but it was
      found to be activated by the pro-inflammatory cytokine TNF-alpha. Forced
      suppression of AMPK, either with a chemical inhibitor or by knockdown, abrogated
      the accelerating effect of lymphocytes on TJ formation. Similar results were also
      observed in a co-culture with lymphocytes and Calu-3 human airway epithelial
      cells, suggesting that the activation of AMPK may be a general mechanism
      underlying lymphocyte-accelerated TJ assembly in different epithelia. These
      results suggest that signals from lymphocytes, such as cytokines, facilitate TJ
      assembly in epithelial cells via the activation of AMPK.

PMID- 20808812
TI  - Age- and gender-related changes in contractile properties of non-atrophied EDL
      muscle.
AB  - BACKGROUND: In humans, ageing causes skeletal muscles to become atrophied, weak,
      and easily fatigued. In rodent studies, ageing has been associated with
      significant muscle atrophy and changes in the contractile properties of the
      muscles. However, it is not entirely clear whether these changes in contractile
      properties can occur before there is significant atrophy, and whether males and
      females are affected differently. METHODS AND RESULTS: We investigated various
      contractile properties of whole isolated fast-twitch EDL muscles from adult (2-6
      months-old) and aged (12-22 months-old) male and female mice. Atrophy was not
      present in the aged mice. Compared with adult mice, EDL muscles of aged mice had
      significantly lower specific force, longer tetanus relaxation times, and lower
      fatiguability. In the properties of absolute force and muscle relaxation times,
      females were affected by ageing to a greater extent than males. Additionally, EDL
      muscles from a separate group of male mice were subjected to eccentric
      contractions of 15% strain, and larger force deficits were found in aged than in
      adult mice. CONCLUSION: Our findings provide further insight into the muscle
      atrophy, weakness and fatiguability experienced by the elderly. We have shown
      that even in the absence of muscle atrophy, there are definite alterations in the
      physiological properties of whole fast-twitch muscle from ageing mice, and for
      some of these properties the alterations are more pronounced in female mice than
      in male mice.

PMID- 20808813
TI  - Survival of the fittest: positive selection of CD4+ T cells expressing a membrane
      bound fusion inhibitor following HIV-1 infection.
AB  - Although a variety of genetic strategies have been developed to inhibit HIV
      replication, few direct comparisons of the efficacy of these inhibitors have been
      carried out. Moreover, most studies have not examined whether genetic inhibitors
      are able to induce a survival advantage that results in an expansion of
      genetically-modified cells following HIV infection. We evaluated the efficacy of
      three leading genetic strategies to inhibit HIV replication: 1) an HIV-1 tat/rev
      specific small hairpin (sh) RNA; 2) an RNA antisense gene specific for the HIV-1
      envelope; and 3) a viral entry inhibitor, maC46. In stably transduced cell lines
      selected such that >95% of cells expressed the genetic inhibitor, the RNA
      antisense envelope and viral entry inhibitor maC46 provided the strongest
      inhibition of HIV-1 replication. However, when mixed populations of transduced
      and untransduced cells were challenged with HIV-1, the maC46 fusion inhibitor
      resulted in highly efficient positive selection of transduced cells, an effect
      that was evident even in mixed populations containing as few as 1% maC46
      expressing cells. The selective advantage of the maC46 fusion inhibitor was also
      observed in HIV-1-infected cultures of primary T lymphocytes as well as in HIV-1
      infected humanized mice. These results demonstrate robust inhibition of HIV
      replication with the fusion inhibitor maC46 and the antisense Env inhibitor, and
      importantly, a survival advantage of cells expressing the maC46 fusion inhibitor
      both in vitro and in vivo. Evaluation of the ability of genetic inhibitors of HIV
      1 replication to confer a survival advantage on genetically-modified cells
      provides unique information not provided by standard techniques that may be
      important in the in vivo efficacy of these genes.

PMID- 20808814
TI  - The tuberculin skin test (TST) is affected by recent BCG vaccination but not by
      exposure to non-tuberculosis mycobacteria (NTM) during early life.
AB  - The tuberculin skin test (TST) is widely used in TB clinics to aid Mycobacterium
      tuberculosis (M.tb) diagnosis, but the definition and the significance of a
      positive test in very young children is still unclear. This study compared the
      TST in Gambian children at 4(1/2) months of age who either received BCG
      vaccination at birth (Group 1) or were BCG naive (Group 2) in order to examine
      the role of BCG vaccination and/or exposure to environmental mycobacteria in TST
      reactivity at this age. Nearly half of the BCG vaccinated children had a positive
      TST (>or=5 mm) whereas all the BCG naive children were non-reactive, confirming
      that recent BCG vaccination affects TST reactivity. The BCG naive children
      demonstrated in vitro PPD responses in peripheral blood in the absence of TST
      reactivity, supporting exposure to and priming by environmental mycobacterial
      antigens. Group 2 were then vaccinated at 4(1/2) months of age and a repeat TST
      was performed at 20-28 months of age. Positive reactivity (>or=5 mm) was evident
      in 11.1% and 12.5% infants from Group 1 and Group 2 respectively suggesting that
      the timing of BCG vaccination had little effect by this age. We further assessed
      for immune correlates in peripheral blood at 4(1/2) months of age. Mycobacterial
      specific IFNgamma responses were greater in TST responders than in non
      responders, although the size of induration did not correlate with IFNgamma.
      However the IFNgamma: IL-10 ratio positively correlated with TST induration
      suggesting that the relationship between PPD induced IFNgamma and IL-10 in the
      peripheral blood may be important in controlling TST reactivity. Collectively
      these data provide further insights into how the TST is regulated in early life,
      and how a positive response might be interpreted.

PMID- 20808815
TI  - Systematic screening of Drosophila deficiency mutations for embryonic phenotypes
      and orphan receptor ligands.
AB  - This paper defines a collection of Drosophila deletion mutations (deficiencies)
      that can be systematically screened for embryonic phenotypes, orphan receptor
      ligands, and genes affecting protein localization. It reports the results of
      deficiency screens we have conducted that have revealed new axon guidance
      phenotypes in the central nervous system and neuromuscular system and permitted a
      quantitative assessment of the number of potential genes involved in regulating
      guidance of specific motor axon branches. Deficiency "kits" that cover the genome
      with a minimum number of lines have been established to facilitate gene mapping.
      These kits cannot be systematically analyzed for phenotypes, however, since
      embryos homozygous for many deficiencies in these kits fail to develop due to the
      loss of key gene products encoded within the deficiency. To create new kits that
      can be screened for phenotype, we have examined the development of the nervous
      system in embryos homozygous for more than 700 distinct deficiency mutations. A
      kit of approximately 400 deficiency lines for which homozygotes have a
      recognizable nervous system and intact body walls encompasses >80% of the genome.
      Here we show examples of screens of this kit for orphan receptor ligands and
      neuronal antigen expression. It can also be used to find genes involved in
      expression, patterning, and subcellular localization of any protein that can be
      visualized by antibody staining. A subset kit of 233 deficiency lines, for which
      homozygotes develop relatively normally to late stage 16, covers approximately
      50% of the genome. We have screened it for axon guidance phenotypes, and we
      present examples of new phenotypes we have identified. The subset kit can be used
      to screen for phenotypes affecting all embryonic organs. In the future, these
      deficiency kits will allow Drosophila researchers to rapidly and efficiently
      execute genome-wide anatomical screens that require examination of individual
      embryos at high magnification.

PMID- 20808816
TI  - Identification of hookworm DAF-16/FOXO response elements and direct gene targets.
AB  - BACKGROUND: The infective stage of the parasitic nematode hookworm is
      developmentally arrested in the environment and needs to infect a specific host
      to complete its life cycle. The canine hookworm (Ancylostoma caninum) is an
      excellent model for investigating human hookworm infections. The transcription
      factor of A. caninum, Ac-DAF-16, which has a characteristic fork head or "winged
      helix" DNA binding domain (DBD), has been implicated in the resumption of
      hookworm development in the host. However, the precise roles of Ac-DAF-16 in
      hookworm parasitism and its downstream targets are unknown. In the present study,
      we combined molecular techniques and bioinformatics to identify a group of Ac-DAF
      16 binding sites and target genes. METHODOLOGY/PRINCIPAL FINDINGS: The DNA
      binding domain of Ac-DAF-16 was used to select genomic fragments by in vitro
      genomic selection. Twenty four bound genomic fragments were analyzed for the
      presence of the DAF-16 family binding element (DBE) and possible alternative Ac
      DAF-16 bind motifs. The 22 genes linked to these genomic fragments were
      identified using bioinformatics tools and defined as candidate direct gene
      targets of Ac-DAF-16. Their developmental stage-specific expression patterns were
      examined. Also, a new putative DAF-16 binding element was identified.
      CONCLUSIONS/SIGNIFICANCE: Our results show that Ac-DAF-16 is involved in diverse
      biological processes throughout hookworm development. Further investigation of
      these target genes will provide insights into the molecular basis by which Ac-DAF
      16 regulates its downstream gene network in hookworm infection.

PMID- 20808817
TI  - A Toxoplasma MORN1 null mutant undergoes repeated divisions but is defective in
      basal assembly, apicoplast division and cytokinesis.
AB  - The membrane occupation and recognition nexus protein 1 (MORN1) is highly
      conserved among apicomplexan parasites and is associated with several structures
      that have a role in cell division. Here we dissected the role of MORN1 using the
      relatively simple budding process of Toxoplasma gondii as a model. Ablation of
      MORN1 in a conditional null mutant resulted in pronounced defects suggesting a
      central role for MORN1 in apicoplast segregation and in daughter cell budding.
      Lack of MORN1 resulted in double-headed parasites. These Janus-headed parasites
      form two complete apical complexes but fail to assemble a basal complex.
      Moreover, these parasites were capable of undergoing several more budding rounds
      resulting in the formation of up to 16-headed parasites conjoined at the basal
      end. Despite this segregation defect, the mother's cytoskeleton was completely
      disassembled in every budding round. Overall this argues that successful
      completion of the budding is not required for cell cycle progression. None of the
      known basal complex components, including a set of recently identified inner
      membrane complex (IMC) proteins, localized correctly in these multi-headed
      parasites. These data suggest that MORN1 is essential for assembly of the basal
      complex, and that lack of the basal complex abolishes the contractile capacity
      assigned to the basal complex late in daughter formation. Consistent with this
      hypothesis we observe that MORN1 mutants fail to efficiently constrict and divide
      the apicoplast. We used the null background provided by the mutant to dissect the
      function of subdomains of the MORN1 protein. This demonstrated that deletion of a
      single MORN domain already prevented the function of MORN1 whereas a critical
      role for the short linker between MORN domains 6 and 7 was identified. In
      conclusion, MORN1 is required for basal complex assembly and loss of MORN1
      results in defects in apicoplast division and daughter segregation.

PMID- 20808818
TI  - Endothelial membrane remodeling is obligate for anti-angiogenic
      radiosensitization during tumor radiosurgery.
AB  - BACKGROUND: While there is significant interest in combining anti-angiogenesis
      therapy with conventional anti-cancer treatment, clinical trials have as of yet
      yielded limited therapeutic gain, mainly because mechanisms of anti-angiogenic
      therapy remain to a large extent unknown. Currently, anti-angiogenic tumor
      therapy is conceptualized to either "normalize" dysfunctional tumor vasculature,
      or to prevent recruitment of circulating endothelial precursors into the tumor.
      An alternative biology, restricted to delivery of anti-angiogenics immediately
      prior to single dose radiotherapy (radiosurgery), is provided in the present
      study. METHODOLOGY/PRINCIPAL FINDINGS: Genetic data indicate an acute wave of
      ceramide-mediated endothelial apoptosis, initiated by acid sphingomyelinase
      (ASMase), regulates tumor stem cell response to single dose radiotherapy,
      obligatory for tumor cure. Here we show VEGF prevented radiation-induced ASMase
      activation in cultured endothelium, occurring within minutes after radiation
      exposure, consequently repressing apoptosis, an event reversible with exogenous
      C(16)-ceramide. Anti-VEGFR2 acts conversely, enhancing ceramide generation and
      apoptosis. In vivo, MCA/129 fibrosarcoma tumors were implanted in asmase(+/+)
      mice or asmase(-/-) littermates and irradiated in the presence or absence of anti
      VEGFR2 DC101 or anti-VEGF G6-31 antibodies. These anti-angiogenic agents, only if
      delivered immediately prior to single dose radiotherapy, de-repressed radiation
      induced ASMase activation, synergistically increasing the endothelial apoptotic
      component of tumor response and tumor cure. Anti-angiogenic radiosensitization
      was abrogated in tumors implanted in asmase(-/-) mice that provide apoptosis
      resistant vasculature, or in wild-type littermates pre-treated with anti-ceramide
      antibody, indicating that ceramide is necessary for this effect.
      CONCLUSIONS/SIGNIFICANCE: These studies show that angiogenic factors fail to
      suppress apoptosis if ceramide remains elevated while anti-angiogenic therapies
      fail without ceramide elevation, defining a ceramide rheostat that determines
      outcome of single dose radiotherapy. Understanding the temporal sequencing of
      anti-angiogenic drugs and radiation enables optimized radiosensitization and
      design of innovative radiosurgery clinical trials.

PMID- 20808819
TI  - The pancreatic and duodenal homeobox protein PDX-1 regulates the ductal specific
      keratin 19 through the degradation of MEIS1 and DNA binding.
AB  - BACKGROUND: Pancreas organogenesis is the result of well-orchestrated and
      balanced activities of transcription factors. The homeobox transcription factor
      PDX-1 plays a crucial role in the development and function of the pancreas, both
      in the maintenance of progenitor cells and in determination and maintenance of
      differentiated endocrine cells. However, the activity of homeobox transcription
      factors requires coordination with co-factors, such as PBX and MEIS proteins. PBX
      and MEIS proteins belong to the family of three amino acid loop extension (TALE)
      homeodomain proteins. In a previous study we found that PDX-1 negatively
      regulates the transcriptional activity of the ductal specific keratin 19 (Krt19).
      In this study, we investigate the role of different domains of PDX-1 and
      elucidate the functional interplay of PDX-1 and MEIS1 necessary for Krt19
      regulation. METHODOLOGY/PRINCIPAL FINDINGS: Here, we demonstrate that PDX-1
      exerts a dual manner of regulation of Krt19 transcriptional activity. Deletion
      studies highlight that the NH(2)-terminus of PDX-1 is functionally relevant for
      the down-regulation of Krt19, as it is required for DNA binding of PDX-1 to the
      Krt19 promoter. Moreover, this effect occurs independently of PBX. Second, we
      provide insight on how PDX-1 regulates the Hox co-factor MEIS1 post
      transcriptionally. We find specific binding of MEIS1 and MEIS2 to the Krt19
      promoter using IP-EMSA, and siRNA mediated silencing of Meis1, but not Meis2,
      reduces transcriptional activation of Krt19 in primary pancreatic ductal cells.
      Over-expression of PDX-1 leads to a decreased level of MEIS1 protein, and this
      decrease is prevented by inhibition of the proteasome. CONCLUSIONS/SIGNIFICANCE:
      Taken together, our data provide evidence for a dual mechanism of how PDX-1
      negatively regulates Krt19 ductal specific gene expression. These findings imply
      that transcription factors may efficiently regulate target gene expression
      through diverse, non-redundant mechanisms.

PMID- 20808820
TI  - Insights into the mechanism of ligand binding to octopine dehydrogenase from
      Pecten maximus by NMR and crystallography.
AB  - Octopine dehydrogenase (OcDH) from the adductor muscle of the great scallop,
      Pecten maximus, catalyzes the NADH dependent, reductive condensation of L
      arginine and pyruvate to octopine, NAD(+), and water during escape swimming
      and/or subsequent recovery. The structure of OcDH was recently solved and a
      reaction mechanism was proposed which implied an ordered binding of NADH, L
      arginine and finally pyruvate. Here, the order of substrate binding as well as
      the underlying conformational changes were investigated by NMR confirming the
      model derived from the crystal structures. Furthermore, the crystal structure of
      the OcDH/NADH/agmatine complex was determined which suggests a key role of the
      side chain of L-arginine in protein cataylsis. Thus, the order of substrate
      binding to OcDH as well as the molecular signals involved in octopine formation
      can now be described in molecular detail.

PMID- 20808821
TI  - Delayed onset of a daytime nap facilitates retention of declarative memory.
AB  - BACKGROUND: Learning followed by a period of sleep, even as little as a nap,
      promotes memory consolidation. It is now generally recognized that sleep
      facilitates the stabilization of information acquired prior to sleep. However,
      the temporal nature of the effect of sleep on retention of declarative memory is
      yet to be understood. We examined the impact of a delayed nap onset on the
      recognition of neutral pictorial stimuli with an added spatial component.
      METHODOLOGY/PRINCIPAL FINDINGS: Participants completed an initial study session
      involving 150 neutral pictures of people, places, and objects. Immediately
      following the picture presentation, participants were asked to make recognition
      judgments on a subset of "old", previously seen, pictures versus intermixed "new"
      pictures. Participants were then divided into one of four groups who either took
      a 90-minute nap immediately, 2 hours, or 4 hours after learning, or remained
      awake for the duration of the experiment. 6 hours after initial learning,
      participants were again tested on the remaining "old" pictures, with "new"
      pictures intermixed. CONCLUSIONS/SIGNIFICANCE: Interestingly, we found a
      stabilizing benefit of sleep on the memory trace reflected as a significant
      negative correlation between the average time elapsed before napping and decline
      in performance from test to retest (p = .001). We found a significant interaction
      between the groups and their performance from test to retest (p = .010), with the
      4-hour delay group performing significantly better than both those who slept
      immediately and those who remained awake (p = .044, p = .010, respectively).
      Analysis of sleep data revealed a significant positive correlation between amount
      of slow wave sleep (SWS) achieved and length of the delay before sleep onset (p =
      .048). The findings add to the understanding of memory processing in humans,
      suggesting that factors such as waking processing and homeostatic increases in
      need for sleep over time modulate the importance of sleep to consolidation of
      neutral declarative memories.

PMID- 20808822
TI  - Does social capital promote physical activity? A population-based study in Japan.
AB  - BACKGROUND: To examine the association between individual-level social capital
      and physical activity. METHODOLOGY/PRINCIPAL FINDINGS: In February 2009, data
      were collected in a population-based cross-sectional survey in Okayama city,
      Japan. A cluster-sampling approach was used to randomly select 4,000 residents
      from 20 school districts. A total of 2260 questionnaires were returned (response
      rate: 57.4%). Individual-level social capital was assessed by an item inquiring
      about perceived trust of others in the community (cognitive dimension of social
      capital) categorized as low trust (43.0%), mid trust (38.6%), and high trust
      (17.3%), as well as participation in voluntary groups (structural dimension of
      social capital), which further distinguished between bonding (8.9%) and bridging
      (27.1%) social capital. Using logistic regression, we calculated the odds ratios
      (ORs) and 95% confidence intervals (CIs) for physical inactivity associated with
      each domain of social capital. Multiple imputation method was employed for
      missing data. Among total participants, 68.8% were physically active and 28.9%
      were inactive. Higher trust was associated with a significantly lower odds of
      physical inactivity (OR = 0.58, 95% CI = 0.42-0.79) compared with low trust. Both
      bridging and bonding social capital were marginally significantly associated with
      lower odds of physical inactivity (bridging, OR = 0.79, 95% CI = 0.62-1.00;
      bonding, OR = 0.71, 95% CI = 0.48-1.03) compared with lack of structural social
      capital. CONCLUSIONS/SIGNIFICANCE: Low individual-level social capital,
      especially lower trust of others in the community, was associated with physical
      inactivity among Japanese adults.

PMID- 20808823
TI  - Dasatinib synergizes with JSI-124 to inhibit growth and migration and induce
      apoptosis of malignant human glioma cells.
AB  - BACKGROUND: Src family kinases (SFK) collectively regulate a variety of cellular
      functions in many cancer types, including proliferation, invasion, motility,
      survival, differentiation, and angiogenesis. Although Dasatinib (BMS-354825), an
      ATP-competitive, small molecule tyrosine kinase inhibitor, suppresses the
      activity of SFKs at nanomolar concentrations, IC50 values for antiproliferative
      effects in glioma cell lines were well above the clinically achievable range,
      suggesting the need to interfere with other components of receptor-induced
      downstream signaling in order to achieve an optimal therapeutic effect. MATERIALS
      AND METHODS: The cytotoxic effects of combining Src and STAT3 inhibition on
      glioma cell lines were evaluated using assays to measure cell proliferation,
      apoptosis and migration. Western blotting and immunocytochemistry was used to
      monitor its effects on cell signaling and morphology. RESULTS: Silencing Src and
      STAT3 expression each partially inhibited cell proliferation and migration. In
      addition, JSI-124 significantly enhanced the efficacy of dasatinib in vitro.
      Combination of dasatinib and JSI-124 achieved significant inhibition of migration
      in all cell lines, which correlated with the inhibition of Src and downstream
      mediators of adhesion (e.g. focal adhesion kinase). Cells exposed to dasatinib
      and JSI-124 exhibited morphological changes that were consistent with an upstream
      role for Src in regulating focal adhesion complexes. CONCLUSIONS: Targeting the
      Src and STAT pathways may contribute to the treatment of cancers that demonstrate
      increased levels of these signaling mediators, including malignant human glioma.
      Clinical studies in these tumor types are warranted.

PMID- 20808824
TI  - Genetic code mutations: the breaking of a three billion year invariance.
AB  - The genetic code has been unchanging for some three billion years in its
      canonical ensemble of encoded amino acids, as indicated by the universal adoption
      of this ensemble by all known organisms. Code mutations beginning with the
      encoding of 4-fluoro-Trp by Bacillus subtilis, initially replacing and eventually
      displacing Trp from the ensemble, first revealed the intrinsic mutability of the
      code. This has since been confirmed by a spectrum of other experimental code
      alterations in both prokaryotes and eukaryotes. To shed light on the experimental
      conversion of a rigidly invariant code to a mutating code, the present study
      examined code mutations determining the propagation of Bacillus subtilis on Trp
      and 4-, 5- and 6-fluoro-tryptophans. The results obtained with the mutants with
      respect to cross-inhibitions between the different indole amino acids, and the
      growth effects of individual nutrient withdrawals rendering essential their
      biosynthetic pathways, suggested that oligogenic barriers comprising sensitive
      proteins which malfunction with amino acid analogues provide effective mechanisms
      for preserving the invariance of the code through immemorial time, and mutations
      of these barriers open up the code to continuous change.

PMID- 20808825
TI  - Novel association strategy with copy number variation for identifying new risk
      Loci of human diseases.
AB  - BACKGROUND: Copy number variations (CNV) are important causal genetic variations
      for human disease; however, the lack of a statistical model has impeded the
      systematic testing of CNVs associated with disease in large-scale cohort.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, we developed a novel integrated strategy to
      test CNV-association in genome-wide case-control studies. We converted the single
      nucleotide polymorphism (SNP) signal to copy number states using a well-trained
      hidden Markov model. We mapped the susceptible CNV-loci through SNP site-specific
      testing to cope with the physiological complexity of CNVs. We also ensured the
      credibility of the associated CNVs through further window-based CNV-pattern
      clustering. Genome-wide data with seven diseases were used to test our strategy
      and, in total, we identified 36 new susceptible loci that are associated with
      CNVs for the seven diseases: 5 with bipolar disorder, 4 with coronary artery
      disease, 1 with Crohn's disease, 7 with hypertension, 9 with rheumatoid
      arthritis, 7 with type 1 diabetes and 3 with type 2 diabetes. Fifteen of these
      identified loci were validated through genotype-association and physiological
      function from previous studies, which provide further confidence for our results.
      Notably, the genes associated with bipolar disorder converged in the
      phosphoinositide/calcium signaling, a well-known affected pathway in bipolar
      disorder, which further supports that CNVs have impact on bipolar disorder.
      CONCLUSIONS/SIGNIFICANCE: Our results demonstrated the effectiveness and
      robustness of our CNV-association analysis and provided an alternative avenue for
      discovering new associated loci of human diseases.

PMID- 20808826
TI  - PLEKHA7 is an adherens junction protein with a tissue distribution and
      subcellular localization distinct from ZO-1 and E-cadherin.
AB  - The pleckstrin-homology-domain-containing protein PLEKHA7 was recently identified
      as a protein linking the E-cadherin-p120 ctn complex to the microtubule
      cytoskeleton. Here we characterize the expression, tissue distribution and
      subcellular localization of PLEKHA7 by immunoblotting, immunofluorescence
      microscopy, immunoelectron microscopy, and northern blotting in mammalian
      tissues. Anti-PLEKHA7 antibodies label the junctional regions of cultured kidney
      epithelial cells by immunofluorescence microscopy, and major polypeptides of M(r)
      approximately 135 kDa and approximately 145 kDa by immunoblotting of lysates of
      cells and tissues. Two PLEKHA7 transcripts ( approximately 5.5 kb and
      approximately 6.5 kb) are detected in epithelial tissues. PLEKHA7 is detected at
      epithelial junctions in sections of kidney, liver, pancreas, intestine, retina,
      and cornea, and its tissue distribution and subcellular localization are distinct
      from ZO-1. For example, PLEKHA7 is not detected within kidney glomeruli.
      Similarly to E-cadherin, p120 ctn, beta-catenin and alpha-catenin, PLEKHA7 is
      concentrated in the apical junctional belt, but unlike these adherens junction
      markers, and similarly to afadin, PLEKHA7 is not localized along the lateral
      region of polarized epithelial cells. Immunoelectron microscopy definitively
      establishes that PLEKHA7 is localized at the adherens junctions in colonic
      epithelial cells, at a mean distance of 28 nm from the plasma membrane. In
      summary, we show that PLEKHA7 is a cytoplasmic component of the epithelial
      adherens junction belt, with a subcellular localization and tissue distribution
      that is distinct from that of ZO-1 and most AJ proteins, and we provide the first
      description of its distribution and localization in several tissues.

PMID- 20808827
TI  - Expression of human frataxin is regulated by transcription factors SRF and TFAP2.
AB  - BACKGROUND: Friedreich ataxia is an autosomal recessive neurodegenerative disease
      caused by reduced expression levels of the frataxin gene (FXN) due to expansion
      of triplet nucleotide GAA repeats in the first intron of FXN. Augmentation of
      frataxin expression levels in affected Friedreich ataxia patient tissues might
      substantially slow disease progression. METHODOLOGY/PRINCIPAL FINDINGS: We
      utilized bioinformatic tools in conjunction with chromatin immunoprecipitation
      and electrophoretic mobility shift assays to identify transcription factors that
      influence transcription of the FXN gene. We found that the transcription factors
      SRF and TFAP2 bind directly to FXN promoter sequences. SRF and TFAP2 binding
      sequences in the FXN promoter enhanced transcription from luciferase constructs,
      while mutagenesis of the predicted SRF or TFAP2 binding sites significantly
      decreased FXN promoter activity. Further analysis demonstrated that robust SRF-
      and TFAP2-mediated transcriptional activity was dependent on a regulatory
      element, located immediately downstream of the first FXN exon. Finally, over
      expression of either SRF or TFAP2 significantly increased frataxin mRNA and
      protein levels in HEK293 cells, and frataxin mRNA levels were also elevated in SH
      SY5Y cells and in Friedreich ataxia patient lymphoblasts transfected with SRF or
      TFAP2. CONCLUSIONS/SIGNIFICANCE: We identified two transcription factors, SRF and
      TFAP2, as well as an intronic element encompassing EGR3-like sequence, that work
      together to regulate expression of the FXN gene. By providing new mechanistic
      insights into the molecular factors influencing frataxin expression, our results
      should aid in the discovery of new therapeutic targets for the treatment of
      Friedreich ataxia.

PMID- 20808828
TI  - Altered ultrasonic vocalization and impaired learning and memory in Angelman
      syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3.
AB  - Angelman syndrome (AS) is a neurobehavioral disorder associated with mental
      retardation, absence of language development, characteristic
      electroencephalography (EEG) abnormalities and epilepsy, happy disposition,
      movement or balance disorders, and autistic behaviors. The molecular defects
      underlying AS are heterogeneous, including large maternal deletions of chromosome
      15q11-q13 (70%), paternal uniparental disomy (UPD) of chromosome 15 (5%),
      imprinting mutations (rare), and mutations in the E6-AP ubiquitin ligase gene
      UBE3A (15%). Although patients with UBE3A mutations have a wide spectrum of
      neurological phenotypes, their features are usually milder than AS patients with
      deletions of 15q11-q13. Using a chromosomal engineering strategy, we generated
      mutant mice with a 1.6-Mb chromosomal deletion from Ube3a to Gabrb3, which
      inactivated the Ube3a and Gabrb3 genes and deleted the Atp10a gene. Homozygous
      deletion mutant mice died in the perinatal period due to a cleft palate resulting
      from the null mutation in Gabrb3 gene. Mice with a maternal deletion (m-/p+) were
      viable and did not have any obvious developmental defects. Expression analysis of
      the maternal and paternal deletion mice confirmed that the Ube3a gene is
      maternally expressed in brain, and showed that the Atp10a and Gabrb3 genes are
      biallelically expressed in all brain sub-regions studied. Maternal (m-/p+), but
      not paternal (m+/p-), deletion mice had increased spontaneous seizure activity
      and abnormal EEG. Extensive behavioral analyses revealed significant impairment
      in motor function, learning and memory tasks, and anxiety-related measures
      assayed in the light-dark box in maternal deletion but not paternal deletion
      mice. Ultrasonic vocalization (USV) recording in newborns revealed that maternal
      deletion pups emitted significantly more USVs than wild-type littermates. The
      increased USV in maternal deletion mice suggests abnormal signaling behavior
      between mothers and pups that may reflect abnormal communication behaviors in
      human AS patients. Thus, mutant mice with a maternal deletion from Ube3a to
      Gabrb3 provide an AS mouse model that is molecularly more similar to the
      contiguous gene deletion form of AS in humans than mice with Ube3a mutation
      alone. These mice will be valuable for future comparative studies to mice with
      maternal deficiency of Ube3a alone.

PMID- 20808829
TI  - Mouse tissues express multiple splice variants of prominin-1.
AB  - Prominin-1, a heavily glycosylated pentaspan membrane protein, is mainly known
      for its function as a marker for (cancer) stem cells, although it can also be
      detected on differentiated cells. Mouse prominin-1 expression is heavily
      regulated by splicing in eight different variants. The function or the expression
      pattern of prominin-1 and its splice variants (SVs) is thus far unknown. In this
      study, we analyzed the expression of the prominin-1 splice variants on mRNA level
      in several mouse tissues and found a broad tissue expression of the majority of
      SVs, but a specific set of SVs had a much more restricted expression profile. For
      instance, the testis expressed only SV3 and SV7. Moreover, SV8 was solely
      detected in the eye. Intriguingly, prominin-1 knockout mice do not suffer from
      gross abnormalities, but do show signs of blindness, which suggest that SV8 has a
      specific function in this tissue. In addition, databases searches for putative
      promoter regions in the mouse prominin-1 gene revealed three potential promoter
      regions that could be linked to specific SVs. Interestingly, for both SV7 and
      SV8, a specific potential promoter region could be identified. To conclude, the
      majority of mouse prominin-1 splice variants are widely expressed in mouse
      tissues. However, specific expression of a few variants, likely driven by
      specific promoters, suggests distinct regulation and a potential important
      function for these variants in certain tissues.

PMID- 20808830
TI  - Transmission of single HIV-1 genomes and dynamics of early immune escape revealed
      by ultra-deep sequencing.
AB  - We used ultra-deep sequencing to obtain tens of thousands of HIV-1 sequences from
      regions targeted by CD8+ T lymphocytes from longitudinal samples from three
      acutely infected subjects, and modeled viral evolution during the critical first
      weeks of infection. Previous studies suggested that a single virus established
      productive infection, but these conclusions were tempered because of limited
      sampling; now, we have greatly increased our confidence in this observation
      through modeling the observed earliest sample diversity based on vastly more
      extensive sampling. Conventional sequencing of HIV-1 from acute/early infection
      has shown different patterns of escape at different epitopes; we investigated the
      earliest escapes in exquisite detail. Over 3-6 weeks, ultradeep sequencing
      revealed that the virus explored an extraordinary array of potential escape
      routes in the process of evading the earliest CD8 T-lymphocyte responses--using
      454 sequencing, we identified over 50 variant forms of each targeted epitope
      during early immune escape, while only 2-7 variants were detected in the same
      samples via conventional sequencing. In contrast to the diversity seen within
      epitopes, non-epitope regions, including the Envelope V3 region, which was
      sequenced as a control in each subject, displayed very low levels of variation.
      In early infection, in the regions sequenced, the consensus forms did not have a
      fitness advantage large enough to trigger reversion to consensus amino acids in
      the absence of immune pressure. In one subject, a genetic bottleneck was
      observed, with extensive diversity at the second time point narrowing to two
      dominant escape forms by the third time point, all within two months of
      infection. Traces of immune escape were observed in the earliest samples,
      suggesting that immune pressure is present and effective earlier than previously
      reported; quantifying the loss rate of the founder virus suggests a direct role
      for CD8 T-lymphocyte responses in viral containment after peak viremia. Dramatic
      shifts in the frequencies of epitope variants during the first weeks of infection
      revealed a complex interplay between viral fitness and immune escape.

PMID- 20808831
TI  - Constitutively nuclear FOXO3a localization predicts poor survival and promotes
      Akt phosphorylation in breast cancer.
AB  - BACKGROUND: The PI3K-Akt signal pathway plays a key role in tumorigenesis and the
      development of drug-resistance. Cytotoxic chemotherapy resistance is linked to
      limited therapeutic options and poor prognosis. METHODOLOGY/PRINCIPAL FINDINGS:
      Examination of FOXO3a and phosphorylated-Akt (P-Akt) expression in breast cancer
      tissue microarrays showed nuclear FOXO3a was associated with lymph node
      positivity (p = 0.052), poor prognosis (p = 0.014), and P-Akt expression in
      invasive ductal carcinoma. Using tamoxifen and doxorubicin-sensitive and 
      resistant breast cancer cell lines as models, we found that doxorubicin- but not
      tamoxifen-resistance is associated with nuclear accumulation of FOXO3a,
      consistent with the finding that sustained nuclear FOXO3a is associated with poor
      prognosis. We also established that doxorubicin treatment induces proliferation
      arrest and FOXO3a nuclear relocation in sensitive breast cancer cells. Induction
      of FOXO3a activity in doxorubicin-sensitive MCF-7 cells was sufficient to promote
      Akt phosphorylation and arrest cell proliferation. Conversely, knockdown of
      endogenous FOXO3a expression reduced PI3K/Akt activity. Using MDA-MB-231 cells,
      in which FOXO3a activity can be induced by 4-hydroxytamoxifen, we showed that
      FOXO3a induction up-regulates PI3K-Akt activity and enhanced doxorubicin
      resistance. However FOXO3a induction has little effect on cell proliferation,
      indicating that FOXO3a or its downstream activity is deregulated in the cytotoxic
      drug resistant breast cancer cells. Thus, our results suggest that sustained
      FOXO3a activation can enhance hyperactivation of the PI3K/Akt pathway.
      CONCLUSIONS/SIGNIFICANCE: Together these data suggest that lymph node metastasis
      and poor survival in invasive ductal breast carcinoma are linked to an uncoupling
      of the Akt-FOXO3a signaling axis. In these breast cancers activated Akt fails to
      inactivate and re-localize FOXO3a to the cytoplasm, and nuclear-targeted FOXO3a
      does not induce cell death or cell cycle arrest. As such, sustained nuclear
      FOXO3a expression in breast cancer may culminate in cancer progression and the
      development of an aggressive phenotype similar to that observed in cytotoxic
      chemotherapy resistant breast cancer cell models.

PMID- 20808833
TI  - Untangling natural seascape variation from marine reserve effects using a
      landscape approach.
AB  - Distinguishing management effects from the inherent variability in a system is a
      key consideration in assessing reserve efficacy. Here, we demonstrate how
      seascape heterogeneity, defined as the spatial configuration and composition of
      coral reef habitats, can mask our ability to discern reserve effects. We then
      test the application of a landscape approach, utilizing advances in benthic
      habitat mapping and GIS techniques, to quantify this heterogeneity and alleviate
      the confounding influence during reserve assessment. Seascape metrics were
      quantified at multiple spatial scales using a combination of spatial image
      analysis and in situ surveys at 87 patch reef sites in Glover's Reef Lagoon,
      Belize, within and outside a marine reserve enforced since 1998. Patch reef sites
      were then clustered into classes sharing similar seascape attributes using
      metrics that correlated significantly to observed variations in both fish and
      coral communities. When the efficacy of the marine reserve was assessed without
      including landscape attributes, no reserve effects were detected in the diversity
      and abundance of fish and coral communities, despite 10 years of management
      protection. However, grouping sites based on landscape attributes revealed
      significant reserve effects between site classes. Fish had higher total biomass
      (1.5x) and commercially important biomass (1.75x) inside the reserve and coral
      cover was 1.8 times greater inside the reserve, though direction and degree of
      response varied by seascape class. Our findings show that the application of a
      landscape classification approach vastly improves our ability to evaluate the
      efficacy of marine reserves by controlling for confounding effects of seascape
      heterogeneity and suggests that landscape heterogeneity should be considered in
      future reserve design.

PMID- 20808832
TI  - Rapid dopaminergic modulation of the fish hypothalamic transcriptome and
      proteome.
AB  - BACKGROUND: Dopamine (DA) is a major neurotransmitter playing an important role
      in the regulation of vertebrate reproduction. We developed a novel method for the
      comparison of transcriptomic and proteomic data obtained from in vivo experiments
      designed to study the neuroendocrine actions of DA. METHODS AND FINDINGS: Female
      goldfish were injected (i.p.) with DA agonists (D1-specific; SKF 38393, or D2
      specific; LY 171555) and sacrificed after 5 h. Serum LH levels were reduced by
      57% and 75% by SKF 38393 and LY 171555, respectively, indicating that the
      treatments produced physiologically relevant responses in vivo. Bioinformatic
      strategies and a ray-finned fish database were established for microarray and
      iTRAQ proteomic analysis of the hypothalamus, revealing a total of 3088 mRNAs and
      42 proteins as being differentially regulated by the treatments. Twenty one
      proteins and mRNAs corresponding to these proteins appeared on both lists. Many
      of the mRNAs and proteins affected by the treatments were grouped into the Gene
      Ontology categorizations of protein complex, signal transduction, response to
      stimulus, and regulation of cellular processes. There was a 57% and 14%
      directional agreement between the differentially-regulated mRNAs and proteins for
      SKF 38393 and LY 171555, respectively. CONCLUSIONS: The results demonstrate the
      applicability of advanced high-throughput genomic and proteomic analyses in an
      amendable well-studied teleost model species whose genome has yet to be
      sequenced. We demonstrate that DA rapidly regulates multiple hypothalamic
      pathways and processes that are also known to be involved in pathologies of the
      central nervous system.

PMID- 20808834
TI  - Mitochondrial DNA variant discovery and evaluation in human Cardiomyopathies
      through next-generation sequencing.
AB  - Mutations in mitochondrial DNA (mtDNA) may cause maternally-inherited
      cardiomyopathy and heart failure. In homoplasmy all mtDNA copies contain the
      mutation. In heteroplasmy there is a mixture of normal and mutant copies of
      mtDNA. The clinical phenotype of an affected individual depends on the type of
      genetic defect and the ratios of mutant and normal mtDNA in affected tissues. We
      aimed at determining the sensitivity of next-generation sequencing compared to
      Sanger sequencing for mutation detection in patients with mitochondrial
      cardiomyopathy. We studied 18 patients with mitochondrial cardiomyopathy and two
      with suspected mitochondrial disease. We "shotgun" sequenced PCR-amplified mtDNA
      and multiplexed using a single run on Roche's 454 Genome Sequencer. By mapping to
      the reference sequence, we obtained 1,300x average coverage per case and
      identified high-confidence variants. By comparing these to >400 mtDNA
      substitution variants detected by Sanger, we found 98% concordance in variant
      detection. Simulation studies showed that >95% of the homoplasmic variants were
      detected at a minimum sequence coverage of 20x while heteroplasmic variants
      required >200x coverage. Several Sanger "misses" were detected by 454 sequencing.
      These included the novel heteroplasmic 7501T>C in tRNA serine 1 in a patient with
      sudden cardiac death. These results support a potential role of next-generation
      sequencing in the discovery of novel mtDNA variants with heteroplasmy below the
      level reliably detected with Sanger sequencing. We hope that this will assist in
      the identification of mtDNA mutations and key genetic determinants for
      cardiomyopathy and mitochondrial disease.

PMID- 20808835
TI  - DNA-triggered aggregation of copper, zinc superoxide dismutase in the presence of
      ascorbate.
AB  - The oxidative damage hypothesis proposed for the function gain of copper, zinc
      superoxide dismutase (SOD1) maintains that both mutant and wild-type (WT) SOD1
      catalyze reactions with abnormal substrates that damage cellular components
      critical for viability of the affected cells. However, whether the oxidative
      damage of SOD1 is involved in the formation of aggregates rich in SOD1 or not
      remains elusive. Here, we sought to explore the oxidative aggregation of WT SOD1
      exposed to environments containing both ascorbate (Asc) and DNA under neutral
      conditions. The results showed that the WT SOD1 protein was oxidized in the
      presence of Asc. The oxidation results in the higher affinity of the modified
      protein for DNA than that of the unmodified protein. The oxidized SOD1 was
      observed to be more prone to aggregation than the WT SOD1, and the addition of
      DNA can significantly accelerate the oxidative aggregation. Moreover, a
      reasonable relationship can be found between the oxidation, increased
      hydrophobicity, and aggregation of SOD1 in the presence of DNA. The crucial step
      in aggregation is neutralization of the positive charges on some SOD1 surfaces by
      DNA binding. This study might be crucial for understanding molecular forces
      driving the protein aggregation.

PMID- 20808836
TI  - Plants modify biological processes to ensure survival following carbon depletion:
      a Lolium perenne model.
AB  - BACKGROUND: Plants, due to their immobility, have evolved mechanisms allowing
      them to adapt to multiple environmental and management conditions. Short-term
      undesirable conditions (e.g. moisture deficit, cold temperatures) generally
      reduce photosynthetic carbon supply while increasing soluble carbohydrate
      accumulation. It is not known, however, what strategies plants may use in the
      long-term to adapt to situations resulting in net carbon depletion (i.e. reduced
      photosynthetic carbon supply and carbohydrate accumulation). In addition, many
      transcriptomic experiments have typically been undertaken under laboratory
      conditions; therefore, long-term acclimation strategies that plants use in
      natural environments are not well understood. METHODOLOGY/PRINCIPAL FINDINGS:
      Perennial ryegrass (Lolium perenne L.) was used as a model plant to define
      whether plants adapt to repetitive carbon depletion and to further elucidate
      their long-term acclimation mechanisms. Transcriptome changes in both lamina and
      stubble tissues of field-grown plants with depleted carbon reserves were
      characterised using reverse transcription-quantitative polymerase chain reaction
      (RT-qPCR). The RT-qPCR data for select key genes indicated that plants reduced
      fructan degradation, and increased photosynthesis and fructan synthesis
      capacities following carbon depletion. This acclimatory response was not
      sufficient to prevent a reduction (P<0.001) in net biomass accumulation, but
      ensured that the plant survived. CONCLUSIONS: Adaptations of plants with depleted
      carbon reserves resulted in reduced post-defoliation carbon mobilization and
      earlier replenishment of carbon reserves, thereby ensuring survival and continued
      growth. These findings will help pave the way to improve plant biomass
      production, for either grazing livestock or biofuel purposes.

PMID- 20808837
TI  - Oligonucleotide frequencies of barcoding loci can discriminate species across
      kingdoms.
AB  - BACKGROUND: DNA barcoding refers to the use of short DNA sequences for rapid
      identification of species. Genetic distance or character attributes of a
      particular barcode locus discriminate the species. We report an efficient
      approach to analyze short sequence data for discrimination between species.
      METHODOLOGY AND PRINCIPAL FINDINGS: A new approach, Oligonucleotide Frequency
      Range (OFR) of barcode loci for species discrimination is proposed. OFR of the
      loci that discriminates between species was characteristic of a species, i.e.,
      the maxima and minima within a species did not overlap with that of other
      species. We compared the species resolution ability of different barcode loci
      using p-distance, Euclidean distance of oligonucleotide frequencies, nucleotide
      character based approach and OFR method. The species resolution by OFR was either
      higher or comparable to the other methods. A short fragment of 126 bp of internal
      transcribed spacer region in ribosomal RNA gene was sufficient to discriminate a
      majority of the species using OFR. CONCLUSIONS/SIGNIFICANCE: Oligonucleotide
      frequency range of a barcode locus can discriminate between species. Ability to
      discriminate species using very short DNA fragments may have wider applications
      in forensic and conservation studies.

PMID- 20808838
TI  - Granuloma formation and host defense in chronic Mycobacterium tuberculosis
      infection requires PYCARD/ASC but not NLRP3 or caspase-1.
AB  - The NLR gene family mediates host immunity to various acute pathogenic stimuli,
      but its role in chronic infection is not known. This paper addressed the role of
      NLRP3 (NALP3), its adaptor protein PYCARD (ASC), and caspase-1 during infection
      with Mycobacterium tuberculosis (Mtb). Mtb infection of macrophages in culture
      induced IL-1beta secretion, and this requires the inflammasome components PYCARD,
      caspase-1, and NLRP3. However, in vivo Mtb aerosol infection of Nlrp3(-/-), Casp
      1(-/-), and WT mice showed no differences in pulmonary IL-1beta production,
      bacterial burden, or long-term survival. In contrast, a significant role was
      observed for Pycard in host protection during chronic Mtb infection, as shown by
      an abrupt decrease in survival of Pycard(-/-) mice. Decreased survival of Pycard(
      /-) animals was associated with defective granuloma formation. These data
      demonstrate that PYCARD exerts a novel inflammasome-independent role during
      chronic Mtb infection by containing the bacteria in granulomas.

PMID- 20808839
TI  - Calcium-activated potassium channels BK and IK1 are functionally expressed in
      human gliomas but do not regulate cell proliferation.
AB  - Gliomas are morbid brain tumors that are extremely resistant to available
      chemotherapy and radiology treatments. Some studies have suggested that calcium
      activated potassium channels contribute to the high proliferative potential of
      tumor cells, including gliomas. However, other publications demonstrated no role
      for these channels or even assigned them antitumorogenic properties. In this work
      we characterized the expression and functional contribution to proliferation of
      Ca(2+)-activated K(+) channels in human glioblastoma cells. Quantitative RT-PCR
      detected transcripts for the big conductance (BK), intermediate conductance
      (IK1), and small conductance (SK2) K(+) channels in two glioblastoma-derived cell
      lines and a surgical sample of glioblastoma multiforme. Functional expression of
      BK and IK1 in U251 and U87 glioma cell lines and primary glioma cultures was
      verified using whole-cell electrophysiological recordings. Inhibitors of BK
      (paxilline and penitrem A) and IK1 channels (clotrimazole and TRAM-34) reduced
      U251 and U87 proliferation in an additive fashion, while the selective blocker of
      SK channels UCL1848 had no effect. However, the antiproliferative properties of
      BK and IK1 inhibitors were seen at concentrations that were higher than those
      necessary to inhibit channel activity. To verify specificity of pharmacological
      agents, we downregulated BK and IK1 channels in U251 cells using gene-specific
      siRNAs. Although siRNA knockdowns caused strong reductions in the BK and IK1
      current densities, neither single nor double gene silencing significantly
      affected rates of proliferation. Taken together, these results suggest that
      Ca(2+)-activated K(+) channels do not play a critical role in proliferation of
      glioma cells and that the effects of pharmacological inhibitors occur through
      their off-target actions.

PMID- 20808840
TI  - Loss of pluripotency in human embryonic stem cells directly correlates with an
      increase in nuclear zinc.
AB  - The pluripotency of human embryonic stem cells (hESCs) is important to
      investigations of early development and to cell replacement therapy, but the
      mechanism behind pluripotency is incompletely understood. Zinc has been shown to
      play a key role in differentiation of non-pluripotent cell types, but here its
      role in hESCs is directly examined. By mapping the distribution of metals in
      hESCs at high resolution by x-ray fluorescence microprobe (XFM) and by analyzing
      subcellular metal content, we have found evidence that loss of pluripotency is
      directly correlated with an increase in nuclear zinc. Zinc elevation not only
      redefines our understanding of the mechanisms that support pluripotency, but also
      may act as a biomarker and an intervention point for stem cell differentiation.

PMID- 20808841
TI  - Membrane invaginations reveal cortical sites that pull on mitotic spindles in one
      cell C. elegans embryos.
AB  - Asymmetric positioning of the mitotic spindle in C. elegans embryos is mediated
      by force-generating complexes that are anchored at the plasma membrane and that
      pull on microtubules growing out from the spindle poles. Although asymmetric
      distribution of the force generators is thought to underlie asymmetric
      positioning of the spindle, the number and location of the force generators has
      not been well defined. In particular, it has not been possible to visualize
      individual force generating events at the cortex. We discovered that perturbation
      of the acto-myosin cortex leads to the formation of long membrane invaginations
      that are pulled from the plasma membrane toward the spindle poles. Several lines
      of evidence show that the invaginations, which also occur in unperturbed embryos
      though at lower frequency, are pulled by the same force generators responsible
      for spindle positioning. Thus, the invaginations serve as a tool to localize the
      sites of force generation at the cortex and allow us to estimate a lower limit on
      the number of cortical force generators within the cell.

PMID- 20808842
TI  - Disruption of PTH receptor 1 in T cells protects against PTH-induced bone loss.
AB  - BACKGROUND: Hyperparathyroidism in humans and continuous parathyroid hormone
      (cPTH) treatment in mice cause bone loss by regulating the production of RANKL
      and OPG by stromal cells (SCs) and osteoblasts (OBs). Recently, it has been
      reported that T cells are required for cPTH to induce bone loss as the binding of
      the T cell costimulatory molecule CD40L to SC receptor CD40 augments SC
      sensitivity to cPTH. However it is unknown whether direct PTH stimulation of T
      cells is required for cPTH to induce bone loss, and whether T cells contribute to
      the bone catabolic activity of PTH with mechanisms other than induction of CD40
      signaling in SCs. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that silencing of
      PTH receptor 1 (PPR) in T cells blocks the bone loss and the osteoclastic
      expansion induced by cPTH, thus demonstrating that PPR signaling in T cells is
      central for PTH-induced reduction of bone mass. Mechanistic studies revealed that
      PTH activation of the T cell PPR stimulates T cell production of the
      osteoclastogenic cytokine tumor necrosis factor alpha (TNF). Attesting to the
      relevance of this effect, disruption of T cell TNF production prevents PTH
      induced bone loss. We also show that a novel mechanism by which TNF mediates PTH
      induced osteoclast formation is upregulation of CD40 expression in SCs, which
      increases their RANKL/OPG production ratio. CONCLUSIONS/SIGNIFICANCE: These
      findings demonstrate that PPR signaling in T cells plays an essential role in PTH
      induced bone loss by promoting T cell production of TNF. A previously unknown
      effect of TNF is to increase SC expression of CD40, which in turn increases SC
      osteoclastogenic activity by upregulating their RANKL/OPG production ratio. PPR
      dependent stimulation of TNF production by T cells and the resulting TNF
      regulation of CD40 signaling in SCs are potential new therapeutic targets for the
      bone loss of hyperparathyroidism.

PMID- 20808843
TI  - MicroRNAs and lung cancer: Biology and applications in diagnosis and prognosis.
AB  - MicroRNAs are tiny non-coding RNA molecules which play important roles in the
      epigenetic control of cellular processes by preventing the translation of
      proteins from messenger RNAs (mRNAs). A single microRNA can target different
      mRNAs, and an mRNA can be targeted by multiple microRNAs. Such complex interplays
      underlie many molecular pathways in cells, and specific roles for many microRNAs
      in physiological as well as pathological phenomena have been identified. Changes
      in expression of microRNAs have been associated with a wide variety of disease
      conditions, and microRNA-based biomarkers are being developed for the
      identification and monitoring of such states. This review provides a general
      overview of the current state of knowledge about the biology of microRNAs, and
      specific information about microRNAs with regard to the diagnosis and prognosis
      of lung cancer.

PMID- 20808844
TI  - Structural alterations in a component of cytochrome c oxidase and molecular
      evolution of pathogenic Neisseria in humans.
AB  - Three closely related bacterial species within the genus Neisseria are of
      importance to human disease and health. Neisseria meningitidis is a major cause
      of meningitis, while Neisseria gonorrhoeae is the agent of the sexually
      transmitted disease gonorrhea and Neisseria lactamica is a common, harmless
      commensal of children. Comparative genomics have yet to yield clear insights into
      which factors dictate the unique host-parasite relationships exhibited by each
      since, as a group, they display remarkable conservation at the levels of
      nucleotide sequence, gene content and synteny. Here, we discovered two rare
      alterations in the gene encoding the CcoP protein component of cytochrome cbb(3)
      oxidase that are phylogenetically informative. One is a single nucleotide
      polymorphism resulting in CcoP truncation that acts as a molecular signature for
      the species N. meningitidis. We go on to show that the ancestral ccoP gene arose
      by a unique gene duplication and fusion event and is specifically and completely
      distributed within species of the genus Neisseria. Surprisingly, we found that
      strains engineered to express either of the two CcoP forms conditionally differed
      in their capacity to support nitrite-dependent, microaerobic growth mediated by
      NirK, a nitrite reductase. Thus, we propose that changes in CcoP domain
      architecture and ensuing alterations in function are key traits in successive,
      adaptive radiations within these metapopulations. These findings provide a
      dramatic example of how rare changes in core metabolic proteins can be connected
      to significant macroevolutionary shifts. They also show how evolutionary change
      at the molecular level can be linked to metabolic innovation and its reversal as
      well as demonstrating how genotype can be used to infer alterations of the
      fitness landscape within a single host.

PMID- 20808845
TI  - Enterohemorrhagic E. coli requires N-WASP for efficient type III translocation
      but not for EspFU-mediated actin pedestal formation.
AB  - Upon infection of mammalian cells, enterohemorrhagic E. coli (EHEC) O157:H7
      utilizes a type III secretion system to translocate the effectors Tir and EspF(U)
      (aka TccP) that trigger the formation of F-actin-rich 'pedestals' beneath bound
      bacteria. EspF(U) is localized to the plasma membrane by Tir and binds the
      nucleation-promoting factor N-WASP, which in turn activates the Arp2/3 actin
      assembly complex. Although N-WASP has been shown to be required for EHEC pedestal
      formation, the precise steps in the process that it influences have not been
      determined. We found that N-WASP and actin assembly promote EHEC-mediated
      translocation of Tir and EspF(U) into mammalian host cells. When we utilized the
      related pathogen enteropathogenic E. coli to enhance type III translocation of
      EHEC Tir and EspF(U), we found surprisingly that actin pedestals were generated
      on N-WASP-deficient cells. Similar to pedestal formation on wild type cells, Tir
      and EspF(U) were the only bacterial effectors required for pedestal formation,
      and the EspF(U) sequences required to interact with N-WASP were found to also be
      essential to stimulate this alternate actin assembly pathway. In the absence of N
      WASP, the Arp2/3 complex was both recruited to sites of bacterial attachment and
      required for actin assembly. Our results indicate that actin assembly facilitates
      type III translocation, and reveal that EspF(U), presumably by recruiting an
      alternate host factor that can signal to the Arp2/3 complex, exhibits remarkable
      versatility in its strategies for stimulating actin polymerization.

PMID- 20808846
TI  - Immune modulation with sulfasalazine attenuates immunopathogenesis but enhances
      macrophage-mediated fungal clearance during Pneumocystis pneumonia.
AB  - Although T cells are critical for host defense against respiratory fungal
      infections, they also contribute to the immunopathogenesis of Pneumocystis
      pneumonia (PcP). However, the precise downstream effector mechanisms by which T
      cells mediate these diverse processes are undefined. In the current study the
      effects of immune modulation with sulfasalazine were evaluated in a mouse model
      of PcP-related Immune Reconstitution Inflammatory Syndrome (PcP-IRIS). Recovery
      of T cell-mediated immunity in Pneumocystis-infected immunodeficient mice
      restored host defense, but also initiated the marked pulmonary inflammation and
      severe pulmonary function deficits characteristic of IRIS. Sulfasalazine produced
      a profound attenuation of IRIS, with the unexpected consequence of accelerated
      fungal clearance. To determine whether macrophage phagocytosis is an effector
      mechanism of T cell-mediated Pneumocystis clearance and whether sulfasalazine
      enhances clearance by altering alveolar macrophage phagocytic activity, a novel
      multispectral imaging flow cytometer-based method was developed to quantify the
      phagocytosis of Pneumocystis in vivo. Following immune reconstitution, alveolar
      macrophages from PcP-IRIS mice exhibited a dramatic increase in their ability to
      actively phagocytose Pneumocystis. Increased phagocytosis correlated temporally
      with fungal clearance, and required the presence of CD4(+) T cells. Sulfasalazine
      accelerated the onset of the CD4(+) T cell-dependent alveolar macrophage
      phagocytic response in PcP-IRIS mice, resulting in enhanced fungal clearance.
      Furthermore, sulfasalazine promoted a TH2-polarized cytokine environment in the
      lung, and sulfasalazine-enhanced phagocytosis of Pneumocystis was associated with
      an alternatively activated alveolar macrophage phenotype. These results provide
      evidence that macrophage phagocytosis is an important in vivo effector mechanism
      for T cell-mediated Pneumocystis clearance, and that macrophage phenotype can be
      altered to enhance phagocytosis without exacerbating inflammation. Immune
      modulation can diminish pulmonary inflammation while preserving host defense, and
      has therapeutic potential for the treatment of PcP-related immunopathogenesis.

PMID- 20808847
TI  - Giardia cyst wall protein 1 is a lectin that binds to curled fibrils of the
      GalNAc homopolymer.
AB  - The infectious and diagnostic stage of Giardia lamblia (also known as G.
      intestinalis or G. duodenalis) is the cyst. The Giardia cyst wall contains
      fibrils of a unique beta-1,3-linked N-acetylgalactosamine (GalNAc) homopolymer
      and at least three cyst wall proteins (CWPs) composed of Leu-rich repeats
      (CWP(LRR)) and a C-terminal conserved Cys-rich region (CWP(CRR)). Our goals were
      to dissect the structure of the cyst wall and determine how it is disrupted
      during excystation. The intact Giardia cyst wall is thin (approximately 400 nm),
      easily fractured by sonication, and impermeable to small molecules. Curled
      fibrils of the GalNAc homopolymer are restricted to a narrow plane and are coated
      with linear arrays of oval-shaped protein complex. In contrast, cyst walls of
      Giardia treated with hot alkali to deproteinate fibrils of the GalNAc homopolymer
      are thick (approximately 1.2 microm), resistant to sonication, and permeable. The
      deproteinated GalNAc homopolymer, which forms a loose lattice of curled fibrils,
      is bound by native CWP1 and CWP2, as well as by maltose-binding protein (MBP)
      fusions containing the full-length CWP1 or CWP1(LRR). In contrast, neither MBP
      alone nor MBP fused to CWP1(CRR) bind to the GalNAc homopolymer. Recombinant CWP1
      binds to the GalNAc homopolymer within secretory vesicles of Giardia encysting in
      vitro. Fibrils of the GalNAc homopolymer are exposed during excystation or by
      treatment of heat-killed cysts with chymotrypsin, while deproteinated fibrils of
      the GalNAc homopolymer are degraded by extracts of Giardia cysts but not
      trophozoites. These results show the Leu-rich repeat domain of CWP1 is a lectin
      that binds to curled fibrils of the GalNAc homopolymer. During excystation, host
      and Giardia proteases appear to degrade bound CWPs, exposing fibrils of the
      GalNAc homopolymer that are digested by a stage-specific glycohydrolase.

PMID- 20808848
TI  - A rapid change in virulence gene expression during the transition from the
      intestinal lumen into tissue promotes systemic dissemination of Salmonella.
AB  - Bacterial pathogens causing systemic disease commonly evolve from organisms
      associated with localized infections but differ from their close relatives in
      their ability to overcome mucosal barriers by mechanisms that remain incompletely
      understood. Here we investigated whether acquisition of a regulatory gene, tviA,
      contributed to the ability of Salmonella enterica serotype Typhi to disseminate
      from the intestine to systemic sites of infection during typhoid fever. To study
      the consequences of acquiring a new regulator by horizontal gene transfer, tviA
      was introduced into the chromosome of S. enterica serotype Typhimurium, a closely
      related pathogen causing a localized gastrointestinal infection in
      immunocompetent individuals. TviA repressed expression of flagellin, a pathogen
      associated molecular pattern (PAMP), when bacteria were grown at osmotic
      conditions encountered in tissue, but not at higher osmolarity present in the
      intestinal lumen. TviA-mediated flagellin repression enabled bacteria to evade
      sentinel functions of human model epithelia and resulted in increased bacterial
      dissemination to the spleen in a chicken model. Collectively, our data point to
      PAMP repression as a novel pathogenic mechanism to overcome the mucosal barrier
      through innate immune evasion.

PMID- 20808849
TI  - Variations in TcdB activity and the hypervirulence of emerging strains of
      Clostridium difficile.
AB  - Hypervirulent strains of Clostridium difficile have emerged over the past decade,
      increasing the morbidity and mortality of patients infected by this opportunistic
      pathogen. Recent work suggested the major C. difficile virulence factor, TcdB,
      from hypervirulent strains (TcdB(HV)) was more cytotoxic in vitro than TcdB from
      historical strains (TcdB(HIST)). The current study investigated the in vivo
      impact of altered TcdB tropism, and the underlying mechanism responsible for the
      differences in activity between the two forms of this toxin. A combination of
      protein sequence analyses, in vivo studies using a Danio rerio model system, and
      cell entry combined with fluorescence assays were used to define the critical
      differences between TcdB(HV) and TcdB(HIST). Sequence analysis found that TcdB
      was the most variable protein expressed from the pathogenicity locus of C.
      difficile. In line with these sequence differences, the in vivo effects of
      TcdB(HV) were found to be substantially broader and more pronounced than those
      caused by TcdB(HIST). The increased toxicity of TcdB(HV) was related to the
      toxin's ability to enter cells more rapidly and at an earlier stage in
      endocytosis than TcdB(HIST). The underlying biochemical mechanism for more rapid
      cell entry was identified in experiments demonstrating that TcdB(HV) undergoes
      acid-induced conformational changes at a pH much higher than that of TcdB(HIST).
      Such pH-related conformational changes are known to be the inciting step in
      membrane insertion and translocation for TcdB. These data provide insight into a
      critical change in TcdB activity that contributes to the emerging hypervirulence
      of C. difficile.

PMID- 20808850
TI  - Regulatory T cells suppress natural killer cells during plasmid DNA vaccination
      in mice, blunting the CD8+ T cell immune response by the cytokine TGFbeta.
AB  - BACKGROUND: CD4(+)CD25(+) regulatory T cells (Tregs) suppress adaptive T cell
      mediated immune responses to self- and foreign-antigens. Tregs may also suppress
      early innate immune responses to vaccine antigens and might decrease vaccine
      efficacy. NK and NKT cells are the first responders after plasmid DNA vaccination
      and are found at the site of inoculation. Earlier reports demonstrated that NKT
      cells could improve plasmid DNA efficacy, a phenomenon not found for NK cells. In
      fact, it has been shown that under certain disease conditions, NK cells are
      suppressed by Tregs via their release of IL-10 and/or TGFbeta. Therefore, we
      tested the hypothesis that NK cell function is suppressed by Tregs in the setting
      of plasmid DNA vaccination. METHODOLOGY/PRINCIPAL FINDINGS: In this study we show
      that Tregs directly inhibit NK cell function during plasmid DNA vaccination by
      suppressing the potentially 10-fold, NK cell-mediated, augmentation of plasmid
      DNA antigen-specific CD8(+) T cells. We found that this phenomenon is dependent
      on the secretion of cytokine TGFbeta by Tregs, and independent of IL-10.
      CONCLUSIONS: Our data indicate a crucial function for Tregs in blocking plasmid
      DNA vaccine-elicited immune responses, revealing potentially novel strategies for
      improving the efficiency of plasmid DNA vaccines including chemical- or antibody
      induced localized blockage of Treg-mediated suppression of NK cells at the site
      of plasmid DNA vaccine inoculation.

PMID- 20808851
TI  - Single-molecule three-color FRET with both negligible spectral overlap and long
      observation time.
AB  - Full understanding of complex biological interactions frequently requires multi
      color detection capability in doing single-molecule fluorescence resonance energy
      transfer (FRET) experiments. Existing single-molecule three-color FRET
      techniques, however, suffer from severe photobleaching of Alexa 488, or its
      alternative dyes, and have been limitedly used for kinetics studies. In this
      work, we developed a single-molecule three-color FRET technique based on the Cy3
      Cy5-Cy7 dye trio, thus providing enhanced observation time and improved data
      quality. Because the absorption spectra of three fluorophores are well separated,
      real-time monitoring of three FRET efficiencies was possible by incorporating the
      alternating laser excitation (ALEX) technique both in confocal microscopy and in
      total-internal-reflection fluorescence (TIRF) microscopy.

PMID- 20808852
TI  - Micro RNAs of Epstein-Barr virus promote cell cycle progression and prevent
      apoptosis of primary human B cells.
AB  - Cellular and viral microRNAs (miRNAs) are involved in many different processes of
      key importance and more than 10,000 miRNAs have been identified so far. In
      general, relatively little is known about their biological functions in mammalian
      cells because their phenotypic effects are often mild and many of their targets
      still await identification. The recent discovery that Epstein-Barr virus (EBV)
      and other herpesviruses produce their own, barely conserved sets of miRNAs
      suggests that these viruses usurp the host RNA silencing machinery to their
      advantage in contrast to the antiviral roles of RNA silencing in plants and
      insects. We have systematically introduced mutations in EBV's precursor miRNA
      transcripts to prevent their subsequent processing into mature viral miRNAs.
      Phenotypic analyses of these mutant derivatives of EBV revealed that the viral
      miRNAs of the BHRF1 locus inhibit apoptosis and favor cell cycle progression and
      proliferation during the early phase of infected human primary B cells. Our
      findings also indicate that EBV's miRNAs are not needed to control the exit from
      latency. The phenotypes of viral miRNAs uncovered by this genetic analysis
      indicate that they contribute to EBV-associated cellular transformation rather
      than regulate viral genes of EBV's lytic phase.

PMID- 20808853
TI  - Genetic versus rearing-environment effects on phenotype: hatchery and natural
      rearing effects on hatchery- and wild-born coho salmon.
AB  - With the current trends in climate and fisheries, well-designed mitigative
      strategies for conserving fish stocks may become increasingly necessary. The poor
      post-release survival of hatchery-reared Pacific salmon indicates that salmon
      enhancement programs require assessment. The objective of this study was to
      determine the relative roles that genotype and rearing environment play in the
      phenotypic expression of young salmon, including their survival, growth,
      physiology, swimming endurance, predator avoidance and migratory behaviour. Wild-
      and hatchery-born coho salmon adults (Oncorhynchus kisutch) returning to the
      Chehalis River in British Columbia, Canada, were crossed to create pure hatchery,
      pure wild, and hybrid offspring. A proportion of the progeny from each cross was
      reared in a traditional hatchery environment, whereas the remaining fry were
      reared naturally in a contained side channel. The resulting phenotypic
      differences between replicates, between rearing environments, and between cross
      types were compared. While there were few phenotypic differences noted between
      genetic groups reared in the same habitat, rearing environment played a
      significant role in smolt size, survival, swimming endurance, predator avoidance
      and migratory behaviour. The lack of any observed genetic differences between
      wild- and hatchery-born salmon may be due to the long-term mixing of these
      genotypes from hatchery introgression into wild populations, or conversely, due
      to strong selection in nature--capable of maintaining highly fit genotypes
      whether or not fish have experienced part of their life history under cultured
      conditions.

PMID- 20808854
TI  - SMA CARNI-VAL trial part I: double-blind, randomized, placebo-controlled trial of
      L-carnitine and valproic acid in spinal muscular atrophy.
AB  - BACKGROUND: Valproic acid (VPA) has demonstrated potential as a therapeutic
      candidate for spinal muscular atrophy (SMA) in vitro and in vivo. METHODS: Two
      cohorts of subjects were enrolled in the SMA CARNIVAL TRIAL, a non-ambulatory
      group of "sitters" (cohort 1) and an ambulatory group of "walkers" (cohort 2).
      Here, we present results for cohort 1: a multicenter phase II randomized double
      blind intention-to-treat protocol in non-ambulatory SMA subjects 2-8 years of
      age. Sixty-one subjects were randomized 1:1 to placebo or treatment for the first
      six months; all received active treatment the subsequent six months. The primary
      outcome was change in the modified Hammersmith Functional Motor Scale (MHFMS)
      score following six months of treatment. Secondary outcomes included safety and
      adverse event data, and change in MHFMS score for twelve versus six months of
      active treatment, body composition, quantitative SMN mRNA levels, maximum ulnar
      CMAP amplitudes, myometry and PFT measures. RESULTS: At 6 months, there was no
      difference in change from the baseline MHFMS score between treatment and placebo
      groups (difference = 0.643, 95% CI = -1.22-2.51). Adverse events occurred in >80%
      of subjects and were more common in the treatment group. Excessive weight gain
      was the most frequent drug-related adverse event, and increased fat mass was
      negatively related to change in MHFMS values (p = 0.0409). Post-hoc analysis
      found that children ages two to three years that received 12 months treatment,
      when adjusted for baseline weight, had significantly improved MHFMS scores (p =
      0.03) compared to those who received placebo the first six months. A linear
      regression analysis limited to the influence of age demonstrates young age as a
      significant factor in improved MHFMS scores (p = 0.007). CONCLUSIONS: This study
      demonstrated no benefit from six months treatment with VPA and L-carnitine in a
      young non-ambulatory cohort of subjects with SMA. Weight gain, age and treatment
      duration were significant confounding variables that should be considered in the
      design of future trials. TRIAL REGISTRY: Clinicaltrials.gov NCT00227266.

PMID- 20808855
TI  - Fatty acid amide hydrolase in prostate cancer: association with disease severity
      and outcome, CB1 receptor expression and regulation by IL-4.
AB  - BACKGROUND: Recent data have indicated that there may be a dysregulation of
      endocannabinoid metabolism in cancer. Here we have investigated the expression of
      the endocannabinoid metabolising enzyme fatty acid amide hydrolase (FAAH) in a
      well characterised tissue microarray from patients diagnosed with prostate cancer
      at transurethral resection for voiding problems. METHODOLOGY/PRINCIPAL FINDINGS:
      FAAH immunoreactivity (FAAH-IR) was assessed in formalin-fixed paraffin-embedded
      non-malignant and tumour cores from 412 patients with prostate cancer. CB(1)
      receptor immunoreactivity (CB(1)IR) scores were available for this dataset. FAAH
      IR was seen in epithelial cells and blood vessel walls but not in the stroma.
      Tumour epithelial FAAH-IR was positively correlated with the disease severity at
      diagnosis (Gleason score, tumour stage, % of the specimen that contained tumour)
      for cases with mid-range CB(1)IR scores, but not for those with high CB(1)IR
      scores. For the 281 cases who only received palliative therapy at the end stages
      of the disease, a high tumour epithelial FAAH-IR was associated with a poor
      disease-specific survival. Multivariate Cox proportional-hazards regression
      analyses indicated that FAAH-IR gave additional prognostic information to that
      provided by CB(1)IR when a midrange, but not a high CB(1)IR cutoff value was
      used. Interleukin-4 (IL-4) receptor IR was found on tumour epithelial cells and
      incubation of prostate cancer PC-3 and R3327 AT1 cells with IL-4 increased their
      FAAH activity. CONCLUSIONS/SIGNIFICANCE: Tumour epithelial FAAH-IR is associated
      with prostate cancer severity and outcome at mid-range, but not high, CB(1)IR
      scores. The correlation with CB(1)IR in the tumour tissue may be related to a
      common local dysregulation by a component of the tumour microenvironment.

PMID- 20808856
TI  - Partitioning of minimotifs based on function with improved prediction accuracy.
AB  - BACKGROUND: Minimotifs are short contiguous peptide sequences in proteins that
      are known to have a function in at least one other protein. One of the principal
      limitations in minimotif prediction is that false positives limit the usefulness
      of this approach. As a step toward resolving this problem we have built,
      implemented, and tested a new data-driven algorithm that reduces false-positive
      predictions. METHODOLOGY/PRINCIPAL FINDINGS: Certain domains and minimotifs are
      known to be strongly associated with a known cellular process or molecular
      function. Therefore, we hypothesized that by restricting minimotif predictions to
      those where the minimotif containing protein and target protein have a related
      cellular or molecular function, the prediction is more likely to be accurate.
      This filter was implemented in Minimotif Miner using function annotations from
      the Gene Ontology. We have also combined two filters that are based on entirely
      different principles and this combined filter has a better predictability than
      the individual components. CONCLUSIONS/SIGNIFICANCE: Testing these functional
      filters on known and random minimotifs has revealed that they are capable of
      separating true motifs from false positives. In particular, for the cellular
      function filter, the percentage of known minimotifs that are not removed by the
      filter is approximately 4.6 times that of random minimotifs. For the molecular
      function filter this ratio is approximately 2.9. These results, together with the
      comparison with the published frequency score filter, strongly suggest that the
      new filters differentiate true motifs from random background with good
      confidence. A combination of the function filters and the frequency score filter
      performs better than these two individual filters.

PMID- 20808858
TI  - A method for the automated, reliable retrieval of publication-citation records.
AB  - BACKGROUND: Publication records and citation indices often are used to evaluate
      academic performance. For this reason, obtaining or computing them accurately is
      important. This can be difficult, largely due to a lack of complete knowledge of
      an individual's publication list and/or lack of time available to manually obtain
      or construct the publication-citation record. While online publication search
      engines have somewhat addressed these problems, using raw search results can
      yield inaccurate estimates of publication-citation records and citation indices.
      METHODOLOGY: In this paper, we present a new, automated method that produces
      estimates of an individual's publication-citation record from an individual's
      name and a set of domain-specific vocabulary that may occur in the individual's
      publication titles. Because this vocabulary can be harvested directly from a
      research web page or online (partial) publication list, our method delivers an
      easy way to obtain estimates of a publication-citation record and the relevant
      citation indices. Our method works by applying a series of stringent name and
      content filters to the raw publication search results returned by an online
      publication search engine. In this paper, our method is run using Google Scholar,
      but the underlying filters can be easily applied to any existing publication
      search engine. When compared against a manually constructed data set of
      individuals and their publication-citation records, our method provides
      significant improvements over raw search results. The estimated publication
      citation records returned by our method have an average sensitivity of 98% and
      specificity of 72% (in contrast to raw search result specificity of less than
      10%). When citation indices are computed using these records, the estimated
      indices are within of the true value 10%, compared to raw search results which
      have overestimates of, on average, 75%. CONCLUSIONS: These results confirm that
      our method provides significantly improved estimates over raw search results, and
      these can either be used directly for large-scale (departmental or university)
      analysis or further refined manually to quickly give accurate publication
      citation records.

PMID- 20808857
TI  - Examination of apoptosis signaling in pancreatic cancer by computational signal
      transduction analysis.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of
      cancer death. Changes in apoptosis signaling in pancreatic cancer result in
      chemotherapy resistance and aggressive growth and metastasizing. The aim of this
      study was to characterize the apoptosis pathway in pancreatic cancer
      computationally by evaluation of experimental data from high-throughput
      technologies and public data bases. Therefore, gene expression analysis of
      microdissected pancreatic tumor tissue was implemented in a model of the
      apoptosis pathway obtained by computational protein interaction prediction.
      METHODOLOGY/PRINCIPAL FINDINGS: Apoptosis pathway related genes were assembled
      from electronic databases. To assess expression of these genes we constructed a
      virtual subarray from a whole genome analysis from microdissected native tumor
      tissue. To obtain a model of the apoptosis pathway, interactions of members of
      the apoptosis pathway were analysed using public databases and computational
      prediction of protein interactions. Gene expression data were implemented in the
      apoptosis pathway model. 19 genes were found differentially expressed and 12
      genes had an already known pathophysiological role in PDAC, such as
      Survivin/BIRC5, BNIP3 and TNF-R1. Furthermore we validated differential
      expression of IL1R2 and Livin/BIRC7 by RT-PCR and immunohistochemistry.
      Implementation of the gene expression data in the apoptosis pathway map suggested
      two higher level defects of the pathway at the level of cell death receptors and
      within the intrinsic signaling cascade consistent with references on apoptosis in
      PDAC. Protein interaction prediction further showed possible new interactions
      between the single pathway members, which demonstrate the complexity of the
      apoptosis pathway. CONCLUSIONS/SIGNIFICANCE: Our data shows that by computational
      evaluation of public accessible data an acceptable virtual image of the apoptosis
      pathway might be given. By this approach we could identify two higher level
      defects of the apoptosis pathway in PDAC. We could further for the first time
      identify IL1R2 as possible candidate gene in PDAC.

PMID- 20808859
TI  - Perceptual compensation is correlated with individuals' "autistic" traits:
      implications for models of sound change.
AB  - Variation is a ubiquitous feature of speech. Listeners must take into account
      context-induced variation to recover the interlocutor's intended message. When
      listeners fail to normalize for context-induced variation properly, deviant
      percepts become seeds for new perceptual and production norms. In question is how
      deviant percepts accumulate in a systematic fashion to give rise to sound change
      (i.e., new pronunciation norms) within a given speech community. The present
      study investigated subjects' classification of /s/ and // before /a/ or /u/
      spoken by a male or a female voice. Building on modern cognitive theories of
      autism-spectrum condition, which see variation in autism-spectrum condition in
      terms of individual differences in cognitive processing style, we established a
      significant correlation between individuals' normalization for phonetic context
      (i.e., whether the following vowel is /a/ or /u/) and talker voice variation
      (i.e., whether the talker is male or female) in speech and their "autistic"
      traits, as measured by the Autism Spectrum Quotient (AQ). In particular, our
      mixed-effect logistic regression models show that women with low AQ (i.e., the
      least "autistic") do not normalize for phonetic coarticulation as much as men and
      high AQ women. This study provides first direct evidence that variability in
      human's ability to compensate for context-induced variations in speech
      perceptually is governed by the individual's sex and cognitive processing style.
      These findings lend support to the hypothesis that the systematic infusion of new
      linguistic variants (i.e., the deviant percepts) originate from a sub-segment of
      the speech community that consistently under-compensates for contextual variation
      in speech.

PMID- 20808861
TI  - Sounds move a static visual object.
AB  - BACKGROUND: Vision provides the most salient information with regard to stimulus
      motion, but audition can also provide important cues that affect visual motion
      perception. Here, we show that sounds containing no motion or positional cues can
      induce illusory visual motion perception for static visual objects.
      METHODOLOGY/PRINCIPAL FINDINGS: Two circles placed side by side were presented in
      alternation producing apparent motion perception and each onset was accompanied
      by a tone burst of a specific and unique frequency. After exposure to this visual
      apparent motion with tones for a few minutes, the tones became drivers for
      illusory motion perception. When the flash onset was synchronized to tones of
      alternating frequencies, a circle blinking at a fixed location was perceived as
      lateral motion in the same direction as the previously exposed apparent motion.
      Furthermore, the effect lasted at least for a few days. The effect was well
      observed at the retinal position that was previously exposed to apparent motion
      with tone bursts. CONCLUSIONS/SIGNIFICANCE: The present results indicate that
      strong association between sound sequence and visual motion is easily formed
      within a short period and that, after forming the association, sounds are able to
      trigger visual motion perception for a static visual object.

PMID- 20808860
TI  - Population genetic analysis of Propionibacterium acnes identifies a subpopulation
      and epidemic clones associated with acne.
AB  - The involvement of Propionibacterium acnes in the pathogenesis of acne is
      controversial, mainly owing to its dominance as an inhabitant of healthy skin.
      This study tested the hypothesis that specific evolutionary lineages of the
      species are associated with acne while others are compatible with health.
      Phylogenetic reconstruction based on nine housekeeping genes was performed on 210
      isolates of P. acnes from well-characterized patients with acne, various
      opportunistic infections, and from healthy carriers. Although evidence of
      recombination was observed, the results showed a basically clonal population
      structure correlated with allelic variation in the virulence genes tly and camp5,
      with pulsed field gel electrophoresis (PFGE)- and biotype, and with expressed
      putative virulence factors. An unexpected geographically and temporal widespread
      dissemination of some clones was demonstrated. The population comprised three
      major divisions, one of which, including an epidemic clone, was strongly
      associated with moderate to severe acne while others were associated with health
      and opportunistic infections. This dichotomy correlated with previously observed
      differences in in vitro inflammation-inducing properties. Comparison of five
      genomes representing acne- and health-associated clones revealed multiple both
      cluster- and strain-specific genes that suggest major differences in ecological
      preferences and redefines the spectrum of disease-associated virulence factors.
      The results of the study indicate that particular clones of P. acnes play an
      etiologic role in acne while others are associated with health.

PMID- 20808862
TI  - Emulsified nanoparticles containing inactivated influenza virus and CpG
      oligodeoxynucleotides critically influences the host immune responses in mice.
AB  - BACKGROUND: Antigen sparing and cross-protective immunity are regarded as crucial
      in pandemic influenza vaccine development. Both targets can be achieved by
      adjuvantation strategy to elicit a robust and broadened immune response. We
      assessed the immunogenicity of an inactivated H5N1 whole-virion vaccine
      (A/Vietnam/1194/2004 NIBRG-14, clade 1) formulated with emulsified nanoparticles
      and investigated whether it can induce cross-clade protecting immunity.
      METHODOLOGY/PRINCIPAL FINDINGS: After formulation with PELC, a proprietary water
      in-oil-in-water nanoemulsion comprising of bioresorbable
      polymer/Span(R)85/squalene, inactivated virus was intramuscularly administered to
      mice in either one-dose or two-dose schedule. We found that the antigen-specific
      serum antibody responses elicited after two doses of non-adjuvanted vaccine were
      lower than those observed after a single dose of adjuvanted vaccine, PELC and the
      conventional alum adjuvant as well. Moreover, 5 microg HA of PELC-formulated
      inactivated virus were capable of inducing higher antibodies than those obtained
      from alum-adjuvanted vaccine. In single-dose study, we found that encapsulating
      inactivated virus into emulsified PELC nanoparticles could induce better antibody
      responses than those formulated with PELC-adsorbed vaccine. However, the potency
      was rather reduced when the inactivated virus and CpG (an immunostimulatory
      oligodeoxynucleotide containing unmethylated cytosine-guanosine motifs) were co
      encapsulated within the emulsion. Finally, the mice who received
      PELC/CpG(adsorption)-vaccine could easily and quickly reach 100% of
      seroprotection against a homologous virus strain and effective cross-protection
      against a heterologous virus strain (A/Whooper swan/Mongolia/244/2005, clade
      2.2). CONCLUSIONS/SIGNIFICANCE: Encapsulating inactivated H5N1 influenza virus
      and CpG into emulsified nanoparticles critically influences the humoral responses
      against pandemic influenza. These results demonstrated that the use of PELC could
      be as antigen-sparing in preparation for a potential shortage of prophylactic
      vaccines against local infectious diseases, in particular pandemic influenza.
      Moreover, the cross-clade neutralizing antibody responses data verify the
      potential of such adjuvanted H5N1 candidate vaccine as an effective tool in pre
      pandemic preparedness.

PMID- 20808863
TI  - 1/f 2 Characteristics and isotropy in the fourier power spectra of visual art,
      cartoons, comics, mangas, and different categories of photographs.
AB  - Art images and natural scenes have in common that their radially averaged (1D)
      Fourier spectral power falls according to a power-law with increasing spatial
      frequency (1/f(2) characteristics), which implies that the power spectra have
      scale-invariant properties. In the present study, we show that other categories
      of man-made images, cartoons and graphic novels (comics and mangas), have similar
      properties. Further on, we extend our investigations to 2D power spectra. In
      order to determine whether the Fourier power spectra of man-made images differed
      from those of other categories of images (photographs of natural scenes, objects,
      faces and plants and scientific illustrations), we analyzed their 2D power
      spectra by principal component analysis. Results indicated that the first fifteen
      principal components allowed a partial separation of the different image
      categories. The differences between the image categories were studied in more
      detail by analyzing whether the mean power and the slope of the power gradients
      from low to high spatial frequencies varied across orientations in the power
      spectra. Mean power was generally higher in cardinal orientations both in real
      world photographs and artworks, with no systematic difference between the two
      types of images. However, the slope of the power gradients showed a lower degree
      of mean variability across spectral orientations (i.e., more isotropy) in art
      images, cartoons and graphic novels than in photographs of comparable subject
      matters. Taken together, these results indicate that art images, cartoons and
      graphic novels possess relatively uniform 1/f(2) characteristics across all
      orientations. In conclusion, the man-made stimuli studied, which were presumably
      produced to evoke pleasant and/or enjoyable visual perception in human observers,
      form a subset of all images and share statistical properties in their Fourier
      power spectra. Whether these properties are necessary or sufficient to induce
      aesthetic perception remains to be investigated.

PMID- 20808864
TI  - IgA anti-beta2-glycoprotein I autoantibodies are associated with an increased
      risk of thromboembolic events in patients with systemic lupus erythematosus.
AB  - BACKGROUND: The clinical utility of testing for antiphospholipid antibodies (aPL)
      of IgA isotype remains controversial. METHODOLOGY/PRINCIPAL FINDINGS: To address
      this issue, we reasoned that if IgA aPL contribute to the clinical manifestations
      of the antiphospholipid syndrome, then an association with thromboembolic events
      should manifest in patients whose only aPL is of IgA isotype. We performed a
      retrospective chart review of 56 patients (31 with systemic lupus erythematosus
      [SLE] and 25 without SLE) whose only positive aPL was IgA anti-beta2-glycoprotein
      I (isolated IgA anti-beta2GPI) and compared their clinical features with 56
      individually matched control patients without any aPL. Patients with isolated IgA
      anti-beta2GPI had a significantly increased number of thromboembolic events, as
      compared to controls. When patients were stratified into those with and without
      SLE, the association between isolated IgA anti-beta2GPI and thromboembolic events
      persisted for patients with SLE, but was lost for those without SLE. Titers of
      IgA anti-beta2GPI were significantly higher in SLE patients who suffered a
      thromboembolic event. Among patients with isolated IgA anti-beta2GPI, there was
      an increased prevalence of diseases or morbidities involving organs of mucosal
      immunity (i.e., gastrointestinal system, pulmonary system, and skin).
      CONCLUSIONS/SIGNIFICANCE: The presence of isolated IgA anti-beta2GPI is
      associated with an increased risk of thromboembolic events, especially among
      patients with SLE. IgA anti-beta2GPI is associated with an increased prevalence
      of morbidities involving organs of mucosal immunity.

PMID- 20808865
TI  - Noncoding RNA mediated traffic of foreign mRNA into chloroplasts reveals a novel
      signaling mechanism in plants.
AB  - Communication between chloroplasts and the nucleus is one of the milestones of
      the evolution of plants on earth. Proteins encoded by ancestral chloroplast
      endogenous genes were transferred to the nucleus during the endosymbiotic
      evolution and originated this communication, which is mainly dependent on
      specific transit-peptides. However, the identification of nuclear-encoded
      proteins targeted to the chloroplast lacking these canonical signals suggests the
      existence of an alternative cellular pathway tuning this metabolic crosstalk. Non
      coding RNAS (NcRNAs) are increasingly recognized as regulators of gene expression
      as they play roles previously believed to correspond to proteins. Avsunviroidae
      family viroids are the only noncoding functional RNAs that have been reported to
      traffic inside the chloroplasts. Elucidating mechanisms used by these pathogens
      to enter this organelle will unearth novel transport pathways in plant cells.
      Here we show that a viroid-derived NcRNA acting as a 5'UTR-end mediates the
      functional import of Green Fluorescent Protein (GFP) mRNA into chloroplast. This
      claim is supported by the observation at confocal microscopy of a selective
      accumulation of GFP in the chloroplast of the leaves expressing the chimeric vd
      5'UTR/GFP and by the detection of the GFP mRNA in chloroplasts isolated from
      cells expressing this construct. These results support the existence of an
      alternative signaling mechanism in plants between the host cell and chloroplasts,
      where an ncRNA functions as a key regulatory molecule to control the accumulation
      of nuclear-encoded proteins in this organelle. In addition, our findings provide
      a conceptual framework to develop new biotechnological tools in systems using
      plant chloroplast as bioreactors. Finally, viroids of the family Avsunviroidae
      have probably evolved to subvert this signaling mechanism to regulate their
      differential traffic into the chloroplast of infected cells.

PMID- 20808866
TI  - Conformational adaptation of Asian macaque TRIMCyp directs lineage specific
      antiviral activity.
AB  - TRIMCyps are anti-retroviral proteins that have arisen independently in New World
      and Old World primates. All TRIMCyps comprise a CypA domain fused to the
      tripartite domains of TRIM5alpha but they have distinct lentiviral specificities,
      conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in
      Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps
      have acquired changes that switch restriction specificity between different
      lentiviral lineages, resulting in species-specific alleles that target different
      viruses. Structural, thermodynamic and viral restriction analysis suggests that a
      single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp
      evolution, expanding restriction specificity to the lentiviral lineages found in
      African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have
      enhanced restriction to particular viruses but at the cost of broad specificity.
      We reveal how specificity is altered by a scaffold mutation, E143K, that modifies
      surface electrostatics and propagates conformational changes into the active
      site. Our results suggest that lentiviruses may have been important pathogens in
      Asian macaques despite the fact that there are no reported lentiviral infections
      in current macaque populations.

PMID- 20808867
TI  - Identification and characterization of an unusual class I myosin involved in
      vesicle traffic in Trypanosoma brucei.
AB  - Myosins are a multimember family of motor proteins with diverse functions in
      eukaryotic cells. African trypanosomes possess only two candidate myosins and
      thus represent a useful system for functional analysis of these motors. One of
      these candidates is an unusual class I myosin (TbMyo1) that is expressed at
      similar levels but organized differently during the life cycle of Trypanosoma
      brucei. This myosin localizes to the polarized endocytic pathway in bloodstream
      forms of the parasite. This organization is actin dependent. Knock down of TbMyo1
      results in a significant reduction in endocytic activity, a cessation in cell
      division and eventually cell death. A striking morphological feature in these
      cells is an enlargement of the flagellar pocket, which is consistent with an
      imbalance in traffic to and from the surface. In contrast TbMyo1 is distributed
      throughout procyclic forms of the tsetse vector and a loss of approximately 90%
      of the protein has no obvious effects on growth or morphology. These results
      reveal a life cycle stage specific requirement for this myosin in essential
      endocytic traffic and represent the first description of the involvement of a
      motor protein in vesicle traffic in these parasites.

PMID- 20808868
TI  - Immunization with pre-erythrocytic antigen CelTOS from Plasmodium falciparum
      elicits cross-species protection against heterologous challenge with Plasmodium
      berghei.
AB  - BACKGROUND: The Plasmodium protein Cell-traversal protein for ookinetes and
      sporozoites (CelTOS) plays an important role in cell traversal of host cells in
      both, mosquito and vertebrates, and is required for successful malaria
      infections. CelTOS is highly conserved among the Plasmodium species, suggesting
      an important functional role across all species. Therefore, targeting the immune
      response to this highly conserved protein and thus potentially interfering with
      its biological function may result in protection against infection even by
      heterologous species of Plasmodium. METHODOLOGY/PRINCIPAL FINDINGS: To test this
      hypothesis, we developed a recombinant codon-harmonized P. falciparum CelTOS
      protein that can be produced to high yields in the E. coli expression system.
      Inbred Balb/c and outbred CD-1 mice were immunized with various doses of the
      recombinant protein adjuvanted with Montanide ISA 720 and characterized using in
      vitro and in vivo analyses. CONCLUSIONS/SIGNIFICANCE: Immunization with PfCelTOS
      resulted in potent humoral and cellular immune responses and most importantly
      induced sterile protection against a heterologous challenge with P. berghei
      sporozoites in a proportion of both inbred and outbred mice. The biological
      activity of CelTOS-specific antibodies against the malaria parasite is likely
      linked to the impairment of sporozoite motility and hepatocyte infectivity. The
      results underscore the potential of this antigen as a pre-erythrocytic vaccine
      candidate and demonstrate for the first time a malaria vaccine that is cross
      protective between species.

PMID- 20808869
TI  - Estimating the accuracy of anal cytology in the presence of an imperfect
      reference standard.
AB  - BACKGROUND: The study aim is to estimate sensitivity and specificity of anal
      cytology for histologic HSIL in analyses adjusted for the imperfect biopsy
      reference standard. METHODS AND PRINCIPAL FINDINGS: Retrospective cohort study of
      an anal dysplasia screening program for HIV infected adults. We estimated the
      prevalence of histologic HSIL by concurrent cytology category and the associated
      cytology ROC area. Cytology operating characteristics for HSIL were estimated and
      adjusted for the imperfect reference standard by 3 methodologies. The study
      cohort included 261 patients with 3 available measures: (1) referral cytology;
      (2) HRA cytology; and (3) HRA directed biopsy. The prevalence of biopsy HSIL
      varied according to the concurrent HRA cytology result: 64.5% for HSIL or ASC-H,
      12.6% for LSIL, 10.9% for ASCUS, and 6.3% for no abnormality. The cytology ROC
      area was 0.78. The observed prevalence of HSIL was 37% (referral cytology), 24%
      (HRA cytology), and 24% (HRA biopsy). Unadjusted estimates of sensitivity and
      specificity of cytology were 0.66 and 0.90, respectively. Adjusted estimates
      varied from 0.47-0.89 (sensitivity) and 0.89-1.0 (specificity). CONCLUSIONS:
      Analysis of a single dataset yields widely different estimates of anal cytology
      operating characteristics that depend on difficult to verify assumptions
      regarding the accuracy of the imperfect reference standard.

PMID- 20808870
TI  - Your resting brain CAREs about your risky behavior.
AB  - BACKGROUND: Research on the neural correlates of risk-related behaviors and
      personality traits has provided insight into mechanisms underlying both normal
      and pathological decision-making. Task-based neuroimaging studies implicate a
      distributed network of brain regions in risky decision-making. What remains to be
      understood are the interactions between these regions and their relation to
      individual differences in personality variables associated with real-world risk
      taking. METHODOLOGY/PRINCIPAL FINDINGS: We employed resting state functional
      magnetic resonance imaging (R-fMRI) and resting state functional connectivity
      (RSFC) methods to investigate differences in the brain's intrinsic functional
      architecture associated with beliefs about the consequences of risky behavior. We
      obtained an individual measure of expected benefit from engaging in risky
      behavior, indicating a risk seeking or risk-averse personality, for each of 21
      participants from whom we also collected a series of R-fMRI scans. The expected
      benefit scores were entered in statistical models assessing the RSFC of brain
      regions consistently implicated in both the evaluation of risk and reward, and
      cognitive control (i.e., orbitofrontal cortex, nucleus accumbens, lateral
      prefrontal cortex, dorsal anterior cingulate). We specifically focused on
      significant brain-behavior relationships that were stable across R-fMRI scans
      collected one year apart. Two stable expected benefit-RSFC relationships were
      observed: decreased expected benefit (increased risk-aversion) was associated
      with 1) stronger positive functional connectivity between right inferior frontal
      gyrus (IFG) and right insula, and 2) weaker negative functional connectivity
      between left nucleus accumbens and right parieto-occipital cortex.
      CONCLUSIONS/SIGNIFICANCE: Task-based activation in the IFG and insula has been
      associated with risk-aversion, while activation in the nucleus accumbens and
      parietal cortex has been associated with both risk seeking and risk-averse
      tendencies. Our results suggest that individual differences in attitudes toward
      risk-taking are reflected in the brain's functional architecture and may have
      implications for engaging in real-world risky behaviors.

PMID- 20808871
TI  - Triggering germination represents a novel strategy to enhance killing of
      Clostridium difficile spores.
AB  - BACKGROUND: Clostridium difficile is an anaerobic, spore-forming bacterium that
      is the most common cause of healthcare-associated diarrhea in developed
      countries. Control of C. difficile is challenging because the spores are
      resistant to killing by alcohol-based hand hygiene products, antimicrobial soaps,
      and most disinfectants. Although initiation of germination has been shown to
      increase susceptibility of spores of other bacterial species to radiation and
      heat, it was not known if triggering of germination could be a useful strategy to
      increase susceptibility of C. difficile spores to radiation or other stressors.
      PRINCIPAL FINDINGS: Here, we demonstrated that exposure of dormant C. difficile
      spores to a germination solution containing amino acids, minerals, and
      taurocholic acid resulted in initiation of germination in room air. Germination
      of spores in room air resulted in significantly enhanced killing by ultraviolet-C
      (UV-C) radiation and heat. On surfaces in hospital rooms, application of
      germination solution resulted in enhanced eradication of spores by UV-C
      administered by an automated room decontamination device. Initiation of
      germination under anaerobic, but not aerobic, conditions resulted in increased
      susceptibility to killing by ethanol, suggesting that exposure to oxygen might
      prevent spores from progressing fully to outgrowth. Stimulation of germination
      also resulted in reduced survival of spores on surfaces in room air, possibly due
      to increased susceptibility to stressors such as oxygen and desiccation.
      CONCLUSIONS: Taken together, these data demonstrate that stimulation of
      germination could represent a novel method to enhance killing of spores by UV-C,
      and suggest the possible application of this strategy as a means to enhance
      killing by other agents.

PMID- 20808872
TI  - A combined epigenetic and non-genetic approach for reprogramming human somatic
      cells.
AB  - Reprogramming of somatic cells to different extents has been reported using
      different methods. However, this is normally accompanied by the use of exogenous
      materials, and the overall reprogramming efficiency has been low. Chemicals and
      small molecules have been used to improve the reprogramming process during
      somatic cell nuclear transfer (SCNT) and induced pluripotent stem (iPS) cell
      generation. We report here the first application of a combined epigenetic and non
      genetic approach for reprogramming somatic cells, i.e., DNA methyltransferase
      (DNMT) and histone deacetylase (HDAC) inhibitors, and human embryonic stem cell
      (hESC) extracts. When somatic cells were pretreated with these inhibitors before
      exposure to hESC (MEL1) extracts, morphological analysis revealed a higher rate
      of hESC-like colony formation than without pretreatment. Quantitative PCR (qPCR)
      demonstrated that pluripotency genes were upregulated when compared to those of
      somatic cells or treated with hESC extracts alone. Overall changes in methylation
      and acetylation levels of pretreated somatic cells suggests that epigenetic
      states of the cells have an effect on reprogramming efficiency induced by hESC
      extracts. KnockOutserum replacement (KOSR) medium (KO-SR) played a positive role
      in inducing expression of the pluripotency genes. hESC extracts could be an
      alternative approach to reprogram somatic cells without introducing exogenous
      materials. The epigenetic pre-treatment of somatic cells could be used to improve
      the efficiency of reprogramming process. Under differentiation conditions, the
      reprogrammed cells exhibited differentiation ability into neurons suggesting
      that, although fully reprogramming was not achieved, the cells could be
      transdifferentiated after reprogramming.

PMID- 20808873
TI  - Diurnal variation in urodynamics of rat.
AB  - In humans, the storage and voiding functions of the urinary bladder have a
      characteristic diurnal variation, with increased voiding during the day and urine
      storage during the night. However, in animal models, the daily functional
      differences in urodynamics have not been well-studied. The goal of this study was
      to identify key urodynamic parameters that vary between day and night. Rats were
      chronically instrumented with an intravesical catheter, and bladder pressure,
      voided volumes, and micturition frequency were measured by continuous filling
      cystometry during the light (inactive) or dark (active) phases of the circadian
      cycle. Cage activity was recorded by video during the experiment. We hypothesized
      that nocturnal rats entrained to a standard 12:12 light:dark cycle would show
      greater ambulatory activity and more frequent, smaller volume micturitions in the
      dark compared to the light. Rats studied during the light phase had a bladder
      capacity of 1.44+/-0.21 mL and voided every 8.2+/-1.2 min. Ambulatory activity
      was lower in the light phase, and rats slept during the recording period,
      awakening only to urinate. In contrast, rats studied during the dark were more
      active, had a lower bladder capacities (0.65+/-0.18 mL), and urinated more often
      (every 3.7+/-0.9 min). Average bladder pressures were not significantly different
      between the light and dark (13.40+/-2.49 and 12.19+/-2.85 mmHg, respectively).
      These results identify a day-night difference in bladder capacity and micturition
      frequency in chronically-instrumented nocturnal rodents that is phase-locked to
      the normal circadian locomotor activity rhythm of the animal. Furthermore, since
      it has generally been assumed that the daily hormonal regulation of renal
      function is a major driver of the circadian rhythm in urination, and few studies
      have addressed the involvement of the lower urinary tract, these results
      establish the bladder itself as a target for circadian regulation.

PMID- 20808874
TI  - Changes in Mycobacterium tuberculosis genotype families over 20 years in a
      population-based study in Northern Malawi.
AB  - BACKGROUND: Despite increasing interest in possible differences in virulence and
      transmissibility between different genotypes of M. tuberculosis, very little is
      known about how genotypes within a population change over decades, or about
      relationships to HIV infection. METHODS AND PRINCIPAL FINDINGS: In a population
      based study in rural Malawi we have examined smears and cultures from
      tuberculosis patients over a 20-year period using spoligotyping. Isolates were
      grouped into spoligotype families and lineages following previously published
      criteria. Time trends, HIV status, drug resistance and outcome were examined by
      spoligotype family and lineage. In addition, transmissibility was examined among
      pairs of cases with known epidemiological contact by assessing the proportion of
      transmissions confirmed for each lineage, on the basis of IS6110 RFLP similarity
      of the M tuberculosis strains. 760 spoligotypes were obtained from smears from
      518 patients from 1986-2002, and 377 spoligotypes from cultures from 347 patients
      from 2005-2008. There was good consistency in patients with multiple specimens.
      Among 781 patients with first episode tuberculosis, the majority (76%) had
      Lineage 4 ("European/American") strains; 9% had Lineage 3 ("East
      African/Indian"); 8% Lineage 1 ("Indo-Oceanic"); and 2% Lineage 2 ("East-Asian");
      others unclassifiable. Over time the proportion of Lineage 4 decreased from >90%
      to 60%, with an increase in the other 3 lineages (p<0.001). Lineage 1 strains
      were more common in those with HIV infection, even after adjusting for age, sex
      and year. There were no associations with drug resistance or outcome, and no
      differences by lineage in the proportion of pairs in which transmission was
      confirmed. CONCLUSIONS: This is the first study to describe long term trends in
      the four M. tuberculosis lineages in a population. Lineage 4 has probably been
      longstanding in this population, with relatively recent introductions and spread
      of Lineages1-3, perhaps influenced by the HIV epidemic.

PMID- 20808875
TI  - Identification of a cardiac specific protein transduction domain by in vivo
      biopanning using a M13 phage peptide display library in mice.
AB  - BACKGROUND: A peptide able to transduce cardiac tissue specifically, delivering
      cargoes to the heart, would be of significant therapeutic potential for delivery
      of small molecules, proteins and nucleic acids. In order to identify peptide(s)
      able to transduce heart tissue, biopanning was performed in cell culture and in
      vivo with a M13 phage peptide display library. METHODS AND RESULTS: A
      cardiomyoblast cell line, H9C2, was incubated with a M13 phage 12 amino acid
      peptide display library. Internalized phage was recovered, amplified and then
      subjected to a total of three rounds of in vivo biopanning where infectious phage
      was isolated from cardiac tissue following intravenous injection. After the third
      round, 60% of sequenced plaques carried the peptide sequence APWHLSSQYSRT, termed
      cardiac targeting peptide (CTP). We demonstrate that CTP was able to transduce
      cardiomyocytes functionally in culture in a concentration and cell-type dependent
      manner. Mice injected with CTP showed significant transduction of heart tissue
      with minimal uptake by lung and kidney capillaries, and no uptake in liver,
      skeletal muscle, spleen or brain. The level of heart transduction by CTP also was
      greater than with a cationic transduction domain. CONCLUSIONS: Biopanning using a
      peptide phage display library identified a peptide able to transduce heart tissue
      in vivo efficiently and specifically. CTP could be used to deliver therapeutic
      peptides, proteins and nucleic acid specifically to the heart.

PMID- 20808876
TI  - CodonTest: modeling amino acid substitution preferences in coding sequences.
AB  - Codon models of evolution have facilitated the interpretation of selective forces
      operating on genomes. These models, however, assume a single rate of non
      synonymous substitution irrespective of the nature of amino acids being
      exchanged. Recent developments have shown that models which allow for amino acid
      pairs to have independent rates of substitution offer improved fit over single
      rate models. However, these approaches have been limited by the necessity for
      large alignments in their estimation. An alternative approach is to assume that
      substitution rates between amino acid pairs can be subdivided into rate classes,
      dependent on the information content of the alignment. However, given the
      combinatorially large number of such models, an efficient model search strategy
      is needed. Here we develop a Genetic Algorithm (GA) method for the estimation of
      such models. A GA is used to assign amino acid substitution pairs to a series of
      rate classes, where is estimated from the alignment. Other parameters of the
      phylogenetic Markov model, including substitution rates, character frequencies
      and branch lengths are estimated using standard maximum likelihood optimization
      procedures. We apply the GA to empirical alignments and show improved model fit
      over existing models of codon evolution. Our results suggest that current models
      are poor approximations of protein evolution and thus gene and organism specific
      multi-rate models that incorporate amino acid substitution biases are preferred.
      We further anticipate that the clustering of amino acid substitution rates into
      classes will be biologically informative, such that genes with similar functions
      exhibit similar clustering, and hence this clustering will be useful for the
      evolutionary fingerprinting of genes.

PMID- 20808877
TI  - Spike-timing theory of working memory.
AB  - Working memory (WM) is the part of the brain's memory system that provides
      temporary storage and manipulation of information necessary for cognition.
      Although WM has limited capacity at any given time, it has vast memory content in
      the sense that it acts on the brain's nearly infinite repertoire of lifetime long
      term memories. Using simulations, we show that large memory content and WM
      functionality emerge spontaneously if we take the spike-timing nature of neuronal
      processing into account. Here, memories are represented by extensively
      overlapping groups of neurons that exhibit stereotypical time-locked
      spatiotemporal spike-timing patterns, called polychronous patterns; and synapses
      forming such polychronous neuronal groups (PNGs) are subject to associative
      synaptic plasticity in the form of both long-term and short-term spike-timing
      dependent plasticity. While long-term potentiation is essential in PNG formation,
      we show how short-term plasticity can temporarily strengthen the synapses of
      selected PNGs and lead to an increase in the spontaneous reactivation rate of
      these PNGs. This increased reactivation rate, consistent with in vivo recordings
      during WM tasks, results in high interspike interval variability and irregular,
      yet systematically changing, elevated firing rate profiles within the neurons of
      the selected PNGs. Additionally, our theory explains the relationship between
      such slowly changing firing rates and precisely timed spikes, and it reveals a
      novel relationship between WM and the perception of time on the order of seconds.

PMID- 20808878
TI  - Mathematical description of bacterial traveling pulses.
AB  - The Keller-Segel system has been widely proposed as a model for bacterial waves
      driven by chemotactic processes. Current experiments on Escherichia coli have
      shown the precise structure of traveling pulses. We present here an alternative
      mathematical description of traveling pulses at the macroscopic scale. This
      modeling task is complemented with numerical simulations in accordance with the
      experimental observations. Our model is derived from an accurate kinetic
      description of the mesoscopic run-and-tumble process performed by bacteria. This
      can account for recent experimental observations with E. coli. Qualitative
      agreements include the asymmetry of the pulse and transition in the collective
      behaviour (clustered motion versus dispersion). In addition, we can capture
      quantitatively the traveling speed of the pulse as well as its characteristic
      length. This work opens several experimental and theoretical perspectives since
      coefficients at the macroscopic level are derived from considerations at the
      cellular scale. For instance, the particular response of a single cell to
      chemical cues turns out to have a strong effect on collective motion.
      Furthermore, the bottom-up scaling allows us to perform preliminary mathematical
      analysis and write efficient numerical schemes. This model is intended as a
      predictive tool for the investigation of bacterial collective motion.

PMID- 20808879
TI  - Use of data-biased random walks on graphs for the retrieval of context-specific
      networks from genomic data.
AB  - Extracting network-based functional relationships within genomic datasets is an
      important challenge in the computational analysis of large-scale data. Although
      many methods, both public and commercial, have been developed, the problem of
      identifying networks of interactions that are most relevant to the given input
      data still remains an open issue. Here, we have leveraged the method of random
      walks on graphs as a powerful platform for scoring network components based on
      simultaneous assessment of the experimental data as well as local network
      connectivity. Using this method, NetWalk, we can calculate distribution of Edge
      Flux values associated with each interaction in the network, which reflects the
      relevance of interactions based on the experimental data. We show that network
      based analyses of genomic data are simpler and more accurate using NetWalk than
      with some of the currently employed methods. We also present NetWalk analysis of
      microarray gene expression data from MCF7 cells exposed to different doses of
      doxorubicin, which reveals a switch-like pattern in the p53 regulated network in
      cell cycle arrest and apoptosis. Our analyses demonstrate the use of NetWalk as a
      valuable tool in generating high-confidence hypotheses from high-content genomic
      data.

PMID- 20808880
TI  - Reduction in learning rates associated with anterograde interference results from
      interactions between different timescales in motor adaptation.
AB  - Prior experiences can influence future actions. These experiences can not only
      drive adaptive changes in motor output, but they can also modulate the rate at
      which these adaptive changes occur. Here we studied anterograde interference in
      motor adaptation--the ability of a previously learned motor task (Task A) to
      reduce the rate of subsequently learning a different (and usually opposite) motor
      task (Task B). We examined the formation of the motor system's capacity for
      anterograde interference in the adaptive control of human reaching-arm movements
      by determining the amount of interference after varying durations of exposure to
      Task A (13, 41, 112, 230, and 369 trials). We found that the amount of
      anterograde interference observed in the learning of Task B increased with the
      duration of Task A. However, this increase did not continue indefinitely;
      instead, the interference reached asymptote after 15-40 trials of Task A.
      Interestingly, we found that a recently proposed multi-rate model of motor
      adaptation, composed of two distinct but interacting adaptive processes, predicts
      several key features of the interference patterns we observed. Specifically, this
      computational model (without any free parameters) predicts the initial growth and
      leveling off of anterograde interference that we describe, as well as the
      asymptotic amount of interference that we observe experimentally (R(2) = 0.91).
      Understanding the mechanisms underlying anterograde interference in motor
      adaptation may enable the development of improved training and rehabilitation
      paradigms that mitigate unwanted interference.

PMID- 20808881
TI  - Quantitative test of the barrier nucleosome model for statistical positioning of
      nucleosomes up- and downstream of transcription start sites.
AB  - The positions of nucleosomes in eukaryotic genomes determine which parts of the
      DNA sequence are readily accessible for regulatory proteins and which are not.
      Genome-wide maps of nucleosome positions have revealed a salient pattern around
      transcription start sites, involving a nucleosome-free region (NFR) flanked by a
      pronounced periodic pattern in the average nucleosome density. While the periodic
      pattern clearly reflects well-positioned nucleosomes, the positioning mechanism
      is less clear. A recent experimental study by Mavrich et al. argued that the
      pattern observed in Saccharomyces cerevisiae is qualitatively consistent with a
      "barrier nucleosome model," in which the oscillatory pattern is created by the
      statistical positioning mechanism of Kornberg and Stryer. On the other hand,
      there is clear evidence for intrinsic sequence preferences of nucleosomes, and it
      is unclear to what extent these sequence preferences affect the observed pattern.
      To test the barrier nucleosome model, we quantitatively analyze yeast nucleosome
      positioning data both up- and downstream from NFRs. Our analysis is based on the
      Tonks model of statistical physics which quantifies the interplay between the
      excluded-volume interaction of nucleosomes and their positional entropy. We find
      that although the typical patterns on the two sides of the NFR are different,
      they are both quantitatively described by the same physical model with the same
      parameters, but different boundary conditions. The inferred boundary conditions
      suggest that the first nucleosome downstream from the NFR (the +1 nucleosome) is
      typically directly positioned while the first nucleosome upstream is
      statistically positioned via a nucleosome-repelling DNA region. These boundary
      conditions, which can be locally encoded into the genome sequence, significantly
      shape the statistical distribution of nucleosomes over a range of up to
      approximately 1,000 bp to each side.

PMID- 20808882
TI  - A cervid vocal fold model suggests greater glottal efficiency in calling at high
      frequencies.
AB  - Male Rocky Mountain elk (Cervus elaphus nelsoni) produce loud and high
      fundamental frequency bugles during the mating season, in contrast to the male
      European Red Deer (Cervus elaphus scoticus) who produces loud and low fundamental
      frequency roaring calls. A critical step in understanding vocal communication is
      to relate sound complexity to anatomy and physiology in a causal manner.
      Experimentation at the sound source, often difficult in vivo in mammals, is
      simulated here by a finite element model of the larynx and a wave propagation
      model of the vocal tract, both based on the morphology and biomechanics of the
      elk. The model can produce a wide range of fundamental frequencies. Low
      fundamental frequencies require low vocal fold strain, but large lung pressure
      and large glottal flow if sound intensity level is to exceed 70 dB at 10 m
      distance. A high-frequency bugle requires both large muscular effort (to strain
      the vocal ligament) and high lung pressure (to overcome phonation threshold
      pressure), but at least 10 dB more intensity level can be achieved. Glottal
      efficiency, the ration of radiated sound power to aerodynamic power at the
      glottis, is higher in elk, suggesting an advantage of high-pitched signaling.
      This advantage is based on two aspects; first, the lower airflow required for
      aerodynamic power and, second, an acoustic radiation advantage at higher
      frequencies. Both signal types are used by the respective males during the mating
      season and probably serve as honest signals. The two signal types relate
      differently to physical qualities of the sender. The low-frequency sound (Red
      Deer call) relates to overall body size via a strong relationship between
      acoustic parameters and the size of vocal organs and body size. The high
      frequency bugle may signal muscular strength and endurance, via a 'vocalizing at
      the edge' mechanism, for which efficiency is critical.

PMID- 20808883
TI  - Reinforcement learning on slow features of high-dimensional input streams.
AB  - Humans and animals are able to learn complex behaviors based on a massive stream
      of sensory information from different modalities. Early animal studies have
      identified learning mechanisms that are based on reward and punishment such that
      animals tend to avoid actions that lead to punishment whereas rewarded actions
      are reinforced. However, most algorithms for reward-based learning are only
      applicable if the dimensionality of the state-space is sufficiently small or its
      structure is sufficiently simple. Therefore, the question arises how the problem
      of learning on high-dimensional data is solved in the brain. In this article, we
      propose a biologically plausible generic two-stage learning system that can
      directly be applied to raw high-dimensional input streams. The system is composed
      of a hierarchical slow feature analysis (SFA) network for preprocessing and a
      simple neural network on top that is trained based on rewards. We demonstrate by
      computer simulations that this generic architecture is able to learn quite
      demanding reinforcement learning tasks on high-dimensional visual input streams
      in a time that is comparable to the time needed when an explicit highly
      informative low-dimensional state-space representation is given instead of the
      high-dimensional visual input. The learning speed of the proposed architecture in
      a task similar to the Morris water maze task is comparable to that found in
      experimental studies with rats. This study thus supports the hypothesis that
      slowness learning is one important unsupervised learning principle utilized in
      the brain to form efficient state representations for behavioral learning.

PMID- 20808884
TI  - Adaptive contact networks change effective disease infectiousness and dynamics.
AB  - Human societies are organized in complex webs that are constantly reshaped by a
      social dynamic which is influenced by the information individuals have about
      others. Similarly, epidemic spreading may be affected by local information that
      makes individuals aware of the health status of their social contacts, allowing
      them to avoid contact with those infected and to remain in touch with the
      healthy. Here we study disease dynamics in finite populations in which infection
      occurs along the links of a dynamical contact network whose reshaping may be
      biased based on each individual's health status. We adopt some of the most widely
      used epidemiological models, investigating the impact of the reshaping of the
      contact network on the disease dynamics. We derive analytical results in the
      limit where network reshaping occurs much faster than disease spreading and
      demonstrate numerically that this limit extends to a much wider range of time
      scales than one might anticipate. Specifically, we show that from a population
      level description, disease propagation in a quickly adapting network can be
      formulated equivalently as disease spreading on a well-mixed population but with
      a rescaled infectiousness. We find that for all models studied here--SI, SIS and
      SIR--the effective infectiousness of a disease depends on the population size,
      the number of infected in the population, and the capacity of healthy individuals
      to sever contacts with the infected. Importantly, we indicate how the use of
      available information hinders disease progression, either by reducing the average
      time required to eradicate a disease (in case recovery is possible), or by
      increasing the average time needed for a disease to spread to the entire
      population (in case recovery or immunity is impossible).

PMID- 20808885
TI  - Modeling chemotaxis reveals the role of reversed phosphotransfer and a bi
      functional kinase-phosphatase.
AB  - Understanding how multiple signals are integrated in living cells to produce a
      balanced response is a major challenge in biology. Two-component signal
      transduction pathways, such as bacterial chemotaxis, comprise histidine protein
      kinases (HPKs) and response regulators (RRs). These are used to sense and respond
      to changes in the environment. Rhodobacter sphaeroides has a complex chemosensory
      network with two signaling clusters, each containing a HPK, CheA. Here we
      demonstrate, using a mathematical model, how the outputs of the two signaling
      clusters may be integrated. We use our mathematical model supported by
      experimental data to predict that: (1) the main RR controlling flagellar
      rotation, CheY(6), aided by its specific phosphatase, the bifunctional kinase
      CheA(3), acts as a phosphate sink for the other RRs; and (2) a phosphorelay
      pathway involving CheB(2) connects the cytoplasmic cluster kinase CheA(3) with
      the polar localised kinase CheA(2), and allows CheA(3)-P to phosphorylate non
      cognate chemotaxis RRs. These two mechanisms enable the bifunctional
      kinase/phosphatase activity of CheA(3) to integrate and tune the sensory output
      of each signaling cluster to produce a balanced response. The signal integration
      mechanisms identified here may be widely used by other bacteria, since like R.
      sphaeroides, over 50% of chemotactic bacteria have multiple cheA homologues and
      need to integrate signals from different sources.

PMID- 20808886
TI  - Ancient protostome origin of chemosensory ionotropic glutamate receptors and the
      evolution of insect taste and olfaction.
AB  - Ionotropic glutamate receptors (iGluRs) are a highly conserved family of ligand
      gated ion channels present in animals, plants, and bacteria, which are best
      characterized for their roles in synaptic communication in vertebrate nervous
      systems. A variant subfamily of iGluRs, the Ionotropic Receptors (IRs), was
      recently identified as a new class of olfactory receptors in the fruit fly,
      Drosophila melanogaster, hinting at a broader function of this ion channel family
      in detection of environmental, as well as intercellular, chemical signals. Here,
      we investigate the origin and evolution of IRs by comprehensive evolutionary
      genomics and in situ expression analysis. In marked contrast to the insect
      specific Odorant Receptor family, we show that IRs are expressed in olfactory
      organs across Protostomia--a major branch of the animal kingdom that encompasses
      arthropods, nematodes, and molluscs--indicating that they represent an ancestral
      protostome chemosensory receptor family. Two subfamilies of IRs are
      distinguished: conserved "antennal IRs," which likely define the first olfactory
      receptor family of insects, and species-specific "divergent IRs," which are
      expressed in peripheral and internal gustatory neurons, implicating this family
      in taste and food assessment. Comparative analysis of drosophilid IRs reveals the
      selective forces that have shaped the repertoires in flies with distinct
      chemosensory preferences. Examination of IR gene structure and genomic
      distribution suggests both non-allelic homologous recombination and retroposition
      contributed to the expansion of this multigene family. Together, these findings
      lay a foundation for functional analysis of these receptors in both
      neurobiological and evolutionary studies. Furthermore, this work identifies novel
      targets for manipulating chemosensory-driven behaviours of agricultural pests and
      disease vectors.

PMID- 20808888
TI  - Something new: an interview with Radoje Drmanac. Interview by Jane Gitschier.

PMID- 20808887
TI  - Genome-wide profiling of p63 DNA-binding sites identifies an element that
      regulates gene expression during limb development in the 7q21 SHFM1 locus.
AB  - Heterozygous mutations in p63 are associated with split hand/foot malformations
      (SHFM), orofacial clefting, and ectodermal abnormalities. Elucidation of the p63
      gene network that includes target genes and regulatory elements may reveal new
      genes for other malformation disorders. We performed genome-wide DNA-binding
      profiling by chromatin immunoprecipitation (ChIP), followed by deep sequencing
      (ChIP-seq) in primary human keratinocytes, and identified potential target genes
      and regulatory elements controlled by p63. We show that p63 binds to an enhancer
      element in the SHFM1 locus on chromosome 7q and that this element controls
      expression of DLX6 and possibly DLX5, both of which are important for limb
      development. A unique micro-deletion including this enhancer element, but not the
      DLX5/DLX6 genes, was identified in a patient with SHFM. Our study strongly
      indicates disruption of a non-coding cis-regulatory element located more than 250
      kb from the DLX5/DLX6 genes as a novel disease mechanism in SHFM1. These data
      provide a proof-of-concept that the catalogue of p63 binding sites identified in
      this study may be of relevance to the studies of SHFM and other congenital
      malformations that resemble the p63-associated phenotypes.

PMID- 20808889
TI  - Epigenetically-inherited centromere and neocentromere DNA replicates earliest in
      S-phase.
AB  - Eukaryotic centromeres are maintained at specific chromosomal sites over many
      generations. In the budding yeast Saccharomyces cerevisiae, centromeres are
      genetic elements defined by a DNA sequence that is both necessary and sufficient
      for function; whereas, in most other eukaryotes, centromeres are maintained by
      poorly characterized epigenetic mechanisms in which DNA has a less definitive
      role. Here we use the pathogenic yeast Candida albicans as a model organism to
      study the DNA replication properties of centromeric DNA. By determining the
      genome-wide replication timing program of the C. albicans genome, we discovered
      that each centromere is associated with a replication origin that is the first to
      fire on its respective chromosome. Importantly, epigenetic formation of new
      ectopic centromeres (neocentromeres) was accompanied by shifts in replication
      timing, such that a neocentromere became the first to replicate and became
      associated with origin recognition complex (ORC) components. Furthermore,
      changing the level of the centromere-specific histone H3 isoform led to a
      concomitant change in levels of ORC association with centromere regions, further
      supporting the idea that centromere proteins determine origin activity. Finally,
      analysis of centromere-associated DNA revealed a replication-dependent sequence
      pattern characteristic of constitutively active replication origins. This strand
      biased pattern is conserved, together with centromere position, among related
      strains and species, in a manner independent of primary DNA sequence. Thus,
      inheritance of centromere position is correlated with a constitutively active
      origin of replication that fires at a distinct early time. We suggest a model in
      which the distinct timing of DNA replication serves as an epigenetic mechanism
      for the inheritance of centromere position.

PMID- 20808890
TI  - The transcriptomes of two heritable cell types illuminate the circuit governing
      their differentiation.
AB  - The differentiation of cells into distinct cell types, each of which is heritable
      for many generations, underlies many biological phenomena. White and opaque cells
      of the fungal pathogen Candida albicans are two such heritable cell types, each
      thought to be adapted to unique niches within their human host. To systematically
      investigate their differences, we performed strand-specific, massively-parallel
      sequencing of RNA from C. albicans white and opaque cells. With these data we
      first annotated the C. albicans transcriptome, finding hundreds of novel
      differentially-expressed transcripts. Using the new annotation, we compared
      differences in transcript abundance between the two cell types with the genomic
      regions bound by a master regulator of the white-opaque switch (Wor1). We found
      that the revised transcriptional landscape considerably alters our understanding
      of the circuit governing differentiation. In particular, we can now resolve the
      poor concordance between binding of a master regulator and the differential
      expression of adjacent genes, a discrepancy observed in several other studies of
      cell differentiation. More than one third of the Wor1-bound differentially
      expressed transcripts were previously unannotated, which explains the formerly
      puzzling presence of Wor1 at these positions along the genome. Many of these
      newly identified Wor1-regulated genes are non-coding and transcribed antisense to
      coding transcripts. We also find that 5' and 3' UTRs of mRNAs in the circuit are
      unusually long and that 5' UTRs often differ in length between cell-types,
      suggesting UTRs encode important regulatory information and that use of
      alternative promoters is widespread. Further analysis revealed that the revised
      Wor1 circuit bears several striking similarities to the Oct4 circuit that
      specifies the pluripotency of mammalian embryonic stem cells. Additional
      characteristics shared with the Oct4 circuit suggest a set of general hallmarks
      characteristic of heritable differentiation states in eukaryotes.

PMID- 20808891
TI  - A global overview of the genetic and functional diversity in the Helicobacter
      pylori cag pathogenicity island.
AB  - The Helicobacter pylori cag pathogenicity island (cagPAI) encodes a type IV
      secretion system. Humans infected with cagPAI-carrying H. pylori are at increased
      risk for sequelae such as gastric cancer. Housekeeping genes in H. pylori show
      considerable genetic diversity; but the diversity of virulence factors such as
      the cagPAI, which transports the bacterial oncogene CagA into host cells, has not
      been systematically investigated. Here we compared the complete cagPAI sequences
      for 38 representative isolates from all known H. pylori biogeographic
      populations. Their gene content and gene order were highly conserved. The
      phylogeny of most cagPAI genes was similar to that of housekeeping genes,
      indicating that the cagPAI was probably acquired only once by H. pylori, and its
      genetic diversity reflects the isolation by distance that has shaped this
      bacterial species since modern humans migrated out of Africa. Most isolates
      induced IL-8 release in gastric epithelial cells, indicating that the function of
      the Cag secretion system has been conserved despite some genetic rearrangements.
      More than one third of cagPAI genes, in particular those encoding cell-surface
      exposed proteins, showed signatures of diversifying (Darwinian) selection at more
      than 5% of codons. Several unknown gene products predicted to be under Darwinian
      selection are also likely to be secreted proteins (e.g. HP0522, HP0535). One of
      these, HP0535, is predicted to code for either a new secreted candidate effector
      protein or a protein which interacts with CagA because it contains two genetic
      lineages, similar to cagA. Our study provides a resource that can guide future
      research on the biological roles and host interactions of cagPAI proteins,
      including several whose function is still unknown.

PMID- 20808892
TI  - Survival and growth of yeast without telomere capping by Cdc13 in the absence of
      Sgs1, Exo1, and Rad9.
AB  - Maintenance of telomere capping is absolutely essential to the survival of
      eukaryotic cells. Telomere capping proteins, such as Cdc13 and POT1, are
      essential for the viability of budding yeast and mammalian cells, respectively.
      Here we identify, for the first time, three genetic modifications that allow
      budding yeast cells to survive without telomere capping by Cdc13. We found that
      simultaneous inactivation of Sgs1, Exo1, and Rad9, three DNA damage response
      (DDR) proteins, is sufficient to allow cell division in the absence of Cdc13.
      Quantitative amplification of ssDNA (QAOS) was used to show that the RecQ
      helicase Sgs1 plays an important role in the resection of uncapped telomeres,
      especially in the absence of checkpoint protein Rad9. Strikingly, simultaneous
      deletion of SGS1 and the nuclease EXO1, further reduces resection at uncapped
      telomeres and together with deletion of RAD9 permits cell survival without CDC13.
      Pulsed-field gel electrophoresis studies show that cdc13-1 rad9Delta sgs1Delta
      exo1Delta strains can maintain linear chromosomes despite the absence of telomere
      capping by Cdc13. However, with continued passage, the telomeres of such strains
      eventually become short and are maintained by recombination-based mechanisms.
      Remarkably, cdc13Delta rad9Delta sgs1Delta exo1Delta strains, lacking any Cdc13
      gene product, are viable and can grow indefinitely. Our work has uncovered a
      critical role for RecQ helicases in limiting the division of cells with uncapped
      telomeres, and this may provide one explanation for increased tumorigenesis in
      human diseases associated with mutations of RecQ helicases. Our results reveal
      the plasticity of the telomere cap and indicate that the essential role of
      telomere capping is to counteract specific aspects of the DDR.

PMID- 20808893
TI  - Microtubule actin crosslinking factor 1 regulates the Balbiani body and animal
      vegetal polarity of the zebrafish oocyte.
AB  - Although of fundamental importance in developmental biology, the genetic basis
      for the symmetry breaking events that polarize the vertebrate oocyte and egg are
      largely unknown. In vertebrates, the first morphological asymmetry in the oocyte
      is the Balbiani body, a highly conserved, transient structure found in
      vertebrates and invertebrates including Drosophila, Xenopus, human, and mouse. We
      report the identification of the zebrafish magellan (mgn) mutant, which exhibits
      a novel enlarged Balbiani body phenotype and a disruption of oocyte polarity. To
      determine the molecular identity of the mgn gene, we positionally cloned the
      gene, employing a novel DNA capture method to target region-specific genomic DNA
      of 600 kb for massively parallel sequencing. Using this technique, we were able
      to enrich for the genomic region linked to our mutation within one week and then
      identify the mutation in mgn using massively parallel sequencing. This is one of
      the first successful uses of genomic DNA enrichment combined with massively
      parallel sequencing to determine the molecular identity of a gene associated with
      a mutant phenotype. We anticipate that the combination of these technologies will
      have wide applicability for the efficient identification of mutant genes in all
      organisms. We identified the mutation in mgn as a deletion in the coding sequence
      of the zebrafish microtubule actin crosslinking factor 1 (macf1) gene. macf1 is a
      member of the highly conserved spectraplakin family of cytoskeletal linker
      proteins, which play diverse roles in polarized cells such as neurons, muscle
      cells, and epithelial cells. In mgn mutants, the oocyte nucleus is mislocalized;
      and the Balbiani body, localized mRNAs, and organelles are absent from the
      periphery of the oocyte, consistent with a function for macf1 in nuclear
      anchoring and cortical localization. These data provide the first evidence for a
      role for spectraplakins in polarization of the vertebrate oocyte and egg.

PMID- 20808894
TI  - Dendritic spikes amplify the synaptic signal to enhance detection of motion in a
      simulation of the direction-selective ganglion cell.
AB  - The On-Off direction-selective ganglion cell (DSGC) in mammalian retinas responds
      most strongly to a stimulus moving in a specific direction. The DSGC initiates
      spikes in its dendritic tree, which are thought to propagate to the soma with
      high probability. Both dendritic and somatic spikes in the DSGC display strong
      directional tuning, whereas somatic PSPs (postsynaptic potentials) are only
      weakly directional, indicating that spike generation includes marked enhancement
      of the directional signal. We used a realistic computational model based on
      anatomical and physiological measurements to determine the source of the
      enhancement. Our results indicate that the DSGC dendritic tree is partitioned
      into separate electrotonic regions, each summing its local excitatory and
      inhibitory synaptic inputs to initiate spikes. Within each local region the local
      spike threshold nonlinearly amplifies the preferred response over the null
      response on the basis of PSP amplitude. Using inhibitory conductances previously
      measured in DSGCs, the simulation results showed that inhibition is only
      sufficient to prevent spike initiation and cannot affect spike propagation.
      Therefore, inhibition will only act locally within the dendritic arbor. We
      identified the role of three mechanisms that generate directional selectivity
      (DS) in the local dendritic regions. First, a mechanism for DS intrinsic to the
      dendritic structure of the DSGC enhances DS on the null side of the cell's
      dendritic tree and weakens it on the preferred side. Second, spatially offset
      postsynaptic inhibition generates robust DS in the isolated dendritic tips but
      weak DS near the soma. Third, presynaptic DS is apparently necessary because it
      is more robust across the dendritic tree. The pre- and postsynaptic mechanisms
      together can overcome the local intrinsic DS. These local dendritic mechanisms
      can perform independent nonlinear computations to make a decision, and there
      could be analogous mechanisms within cortical circuitry.

PMID- 20808895
TI  - The synthetic bacterial lipopeptide Pam3CSK4 modulates respiratory syncytial
      virus infection independent of TLR activation.
AB  - Respiratory syncytial virus (RSV) is an important cause of acute respiratory
      disease in infants, immunocompromised subjects and the elderly. However, it is
      unclear why most primary RSV infections are associated with relatively mild
      symptoms, whereas some result in severe lower respiratory tract infections and
      bronchiolitis. Since RSV hospitalization has been associated with respiratory
      bacterial co-infections, we have tested if bacterial Toll-like receptor (TLR)
      agonists influence RSV-A2-GFP infection in human primary cells or cell lines. The
      synthetic bacterial lipopeptide Pam3-Cys-Ser-Lys4 (Pam3CSK4), the prototype
      ligand for the heterodimeric TLR1/TLR2 complex, enhanced RSV infection in primary
      epithelial, myeloid and lymphoid cells. Surprisingly, enhancement was optimal
      when lipopeptides and virus were added simultaneously, whereas addition of
      Pam3CSK4 immediately after infection had no effect. We have identified two
      structurally related lipopeptides without TLR-signaling capacity that also
      modulate RSV infection, whereas Pam3CSK4-reminiscent TLR1/2 agonists did not, and
      conclude that modulation of infection is independent of TLR activation. A similar
      TLR-independent enhancement of infection could also be demonstrated for wild-type
      RSV strains, and for HIV-1, measles virus and human metapneumovirus. We show that
      the effect of Pam3CSK4 is primarily mediated by enhanced binding of RSV to its
      target cells. The N-palmitoylated cysteine and the cationic lysines were
      identified as pivotal for enhanced virus binding. Surprisingly, we observed
      inhibition of RSV infection in immortalized epithelial cell lines, which was
      shown to be related to interactions between Pam3CSK4 and negatively charged
      glycosaminoglycans on these cells, which are known targets for binding of
      laboratory-adapted but not wild-type RSV. These data suggest a potential role for
      bacterial lipopeptides in enhanced binding of RSV and other viruses to their
      target cells, thus affecting viral entry or spread independent of TLR signaling.
      Moreover, our results also suggest a potential application for these synthetic
      lipopeptides as adjuvants for live-attenuated viral vaccines.

PMID- 20808896
TI  - "Everything you always wanted to know about sex (but were afraid to ask)" in
      Leishmania after two decades of laboratory and field analyses.
AB  - Leishmaniases remain a major public health problem today (350 million people at
      risk, 12 million infected, and 2 million new infections per year). Despite the
      considerable progress in cellular and molecular biology and in evolutionary
      genetics since 1990, the debate on the population structure and reproductive mode
      of Leishmania is far from being settled and therefore deserves further
      investigation. Two major hypotheses coexist: clonality versus sexuality. However,
      because of the lack of clear evidence (experimental or biological confirmation)
      of sexuality in Leishmania parasites, until today it has been suggested and even
      accepted that Leishmania species were mainly clonal with infrequent genetic
      recombination (see [1] for review). Two recent publications, one on Leishmania
      major (an in vitro experimental study) and one on Leishmania braziliensis (a
      population genetics analysis), once again have challenged the hypothesis of
      clonal reproduction. Indeed, the first study experimentally evidenced genetic
      recombination and proposed that Leishmania parasites are capable of having a
      sexual cycle consistent with meiotic processes inside the insect vector. The
      second investigation, based on population genetics studies, showed strong
      homozygosities, an observation that is incompatible with a predominantly clonal
      mode of reproduction at an ecological time scale (approximately 20-500
      generations). These studies highlight the need to advance the knowledge of
      Leishmania biology. In this paper, we first review the reasons stimulating the
      continued debate and then detail the next essential steps to be taken to clarify
      the Leishmania reproduction model. Finally, we widen the discussion to other
      Trypanosomatidae and show that the progress in Leishmania biology can improve our
      knowledge of the evolutionary genetics of American and African trypanosomes.

PMID- 20808898
TI  - Tuberous sclerosis complex 1 regulates dE2F1 expression during development and
      cooperates with RBF1 to control proliferation and survival.
AB  - Previous studies in Drosophila melanogaster have demonstrated that many tumor
      suppressor pathways impinge on Rb/E2F to regulate proliferation and survival.
      Here, we report that Tuberous Sclerosis Complex 1 (TSC1), a well-established
      tumor suppressor that regulates cell size, is an important regulator of dE2F1
      during development. In eye imaginal discs, the loss of tsc1 cooperates with rbf1
      mutations to promote ectopic S-phase and cell death. This cooperative effect
      between tsc1 and rbf1 mutations can be explained, at least in part, by the
      observation that TSC1 post-transcriptionally regulates dE2F1 expression. Clonal
      analysis revealed that the protein level of dE2F1 is increased in tsc1 or tsc2
      mutant cells and conversely decreased in rheb or dTor mutant cells.
      Interestingly, while s6k mutations have no effect on dE2F1 expression in the wild
      type background, S6k is absolutely required for the increase of dE2F1 expression
      in tsc2 mutant cells. The canonical TSC/Rheb/Tor/S6k pathway is also an important
      determinant of dE2F1-dependent cell death, since rheb or s6k mutations suppress
      the developmentally regulated cell death observed in rbf1 mutant eye discs. Our
      results provide evidence to suggest that dE2F1 is an important cell cycle
      regulator that translates the growth-promoting signal downstream of the
      TSC/Rheb/Tor/S6k pathway.

PMID- 20808897
TI  - Disease-associated mutations that alter the RNA structural ensemble.
AB  - Genome-wide association studies (GWAS) often identify disease-associated
      mutations in intergenic and non-coding regions of the genome. Given the high
      percentage of the human genome that is transcribed, we postulate that for some
      observed associations the disease phenotype is caused by a structural
      rearrangement in a regulatory region of the RNA transcript. To identify such
      mutations, we have performed a genome-wide analysis of all known disease
      associated Single Nucleotide Polymorphisms (SNPs) from the Human Gene Mutation
      Database (HGMD) that map to the untranslated regions (UTRs) of a gene. Rather
      than using minimum free energy approaches (e.g. mFold), we use a partition
      function calculation that takes into consideration the ensemble of possible RNA
      conformations for a given sequence. We identified in the human genome disease
      associated SNPs that significantly alter the global conformation of the UTR to
      which they map. For six disease-states (Hyperferritinemia Cataract Syndrome, beta
      Thalassemia, Cartilage-Hair Hypoplasia, Retinoblastoma, Chronic Obstructive
      Pulmonary Disease (COPD), and Hypertension), we identified multiple SNPs in UTRs
      that alter the mRNA structural ensemble of the associated genes. Using a
      Boltzmann sampling procedure for sub-optimal RNA structures, we are able to
      characterize and visualize the nature of the conformational changes induced by
      the disease-associated mutations in the structural ensemble. We observe in
      several cases (specifically the 5' UTRs of FTL and RB1) SNP-induced
      conformational changes analogous to those observed in bacterial regulatory
      Riboswitches when specific ligands bind. We propose that the UTR and SNP
      combinations we identify constitute a "RiboSNitch," that is a regulatory RNA in
      which a specific SNP has a structural consequence that results in a disease
      phenotype. Our SNPfold algorithm can help identify RiboSNitches by leveraging
      GWAS data and an analysis of the mRNA structural ensemble.

PMID- 20808899
TI  - Functional characterisation and drug target validation of a mitotic kinesin-13 in
      Trypanosoma brucei.
AB  - Mitotic kinesins are essential for faithful chromosome segregation and cell
      proliferation. Therefore, in humans, kinesin motor proteins have been identified
      as anti-cancer drug targets and small molecule inhibitors are now tested in
      clinical studies. Phylogenetic analyses have assigned five of the approximately
      fifty kinesin motor proteins coded by Trypanosoma brucei genome to the Kinesin-13
      family. Kinesins of this family have unusual biochemical properties because they
      do not transport cargo along microtubules but are able to depolymerise
      microtubules at their ends, therefore contributing to the regulation of
      microtubule length. In other eukaryotic genomes sequenced to date, only between
      one and three Kinesin-13s are present. We have used immunolocalisation, RNAi
      mediated protein depletion, biochemical in vitro assays and a mouse model of
      infection to study the single mitotic Kinesin-13 in T. brucei. Subcellular
      localisation of all five T. brucei Kinesin-13s revealed distinct distributions,
      indicating that the expansion of this kinesin family in kinetoplastids is
      accompanied by functional diversification. Only a single kinesin (TbKif13-1) has
      a nuclear localisation. Using active, recombinant TbKif13-1 in in vitro assays we
      experimentally confirm the depolymerising properties of this kinesin. We analyse
      the biological function of TbKif13-1 by RNAi-mediated protein depletion and show
      its central role in regulating spindle assembly during mitosis. Absence of the
      protein leads to abnormally long and bent mitotic spindles, causing chromosome
      mis-segregation and cell death. RNAi-depletion in a mouse model of infection
      completely prevents infection with the parasite. Given its essential role in
      mitosis, proliferation and survival of the parasite and the availability of a
      simple in vitro activity assay, TbKif13-1 has been identified as an excellent
      potential drug target.

PMID- 20808900
TI  - Contribution of herpesvirus specific CD8 T cells to anti-viral T cell response in
      humans.
AB  - Herpesviruses infect most humans. Their infections can be associated with
      pathological conditions and significant changes in T cell repertoire but
      evidences of symbiotic effects of herpesvirus latency have never been
      demonstrated. We tested the hypothesis that HCMV and EBV-specific CD8 T cells
      contribute to the heterologous anti-viral immune response. Volume of
      activated/proliferating virus-specific and total CD8 T cells was evaluated in 50
      patients with acute viral infections: 20 with HBV, 12 with Dengue, 12 with
      Influenza, 3 with Adenovirus infection and 3 with fevers of unknown etiology.
      Virus-specific (EBV, HCMV, Influenza) pentamer+ and total CD8 T cells were
      analyzed for activation (CD38/HLA-DR), proliferation (Ki-67/Bcl-2(low)) and
      cytokine production. We observed that all acute viral infections trigger an
      expansion of activated/proliferating CD8 T cells, which differs in size depending
      on the infection but is invariably inflated by CD8 T cells specific for
      persistent herpesviruses (HCMV/EBV). CD8 T cells specific for other non-related
      non persistent viral infection (i.e. Influenza) were not activated. IL-15, which
      is produced during acute viral infections, is the likely contributing mechanism
      driving the selective activation of herpesvirus specific CD8 T cells. In addition
      we were able to show that herpesvirus specific CD8 T cells displayed an increased
      ability to produce the anti-viral cytokine interferon-gamma during the acute
      phase of heterologous viral infection. Taken together, these data demonstrated
      that activated herpesvirus specific CD8 T cells inflate the
      activated/proliferating CD8 T cells population present during acute viral
      infections in human and can contribute to the heterologous anti-viral T cell
      response.

PMID- 20808901
TI  - Damaged intestinal epithelial integrity linked to microbial translocation in
      pathogenic simian immunodeficiency virus infections.
AB  - The chronic phase of HIV infection is marked by pathological activation of the
      immune system, the extent of which better predicts disease progression than
      either plasma viral load or CD4(+) T cell count. Recently, translocation of
      microbial products from the gastrointestinal tract has been proposed as an
      underlying cause of this immune activation, based on indirect evidence including
      the detection of microbial products and specific immune responses in the plasma
      of chronically HIV-infected humans or SIV-infected Asian macaques. We analyzed
      tissues from SIV-infected rhesus macaques (RMs) to provide direct in situ
      evidence for translocation of microbial constituents from the lumen of the
      intestine into the lamina propria and to draining and peripheral lymph nodes and
      liver, accompanied by local immune responses in affected tissues. In chronically
      SIV-infected RMs this translocation is associated with breakdown of the integrity
      of the epithelial barrier of the gastrointestinal (GI) tract and apparent
      inability of lamina propria macrophages to effectively phagocytose translocated
      microbial constituents. By contrast, in the chronic phase of SIV infection in
      sooty mangabeys, we found no evidence of epithelial barrier breakdown, no
      increased microbial translocation and no pathological immune activation. Because
      immune activation is characteristic of the chronic phase of progressive HIV/SIV
      infections, these findings suggest that increased microbial translocation from
      the GI tract, in excess of capacity to clear the translocated microbial
      constituents, helps drive pathological immune activation. Novel therapeutic
      approaches to inhibit microbial translocation and/or attenuate chronic immune
      activation in HIV-infected individuals may complement treatments aimed at direct
      suppression of viral replication.

PMID- 20808902
TI  - HIV-1 Populations in Semen Arise through Multiple Mechanisms.
AB  - HIV-1 is present in anatomical compartments and bodily fluids. Most transmissions
      occur through sexual acts, making virus in semen the proximal source in male
      donors. We find three distinct relationships in comparing viral RNA populations
      between blood and semen in men with chronic HIV-1 infection, and we propose that
      the viral populations in semen arise by multiple mechanisms including: direct
      import of virus, oligoclonal amplification within the seminal tract, or
      compartmentalization. In addition, we find significant enrichment of six out of
      nineteen cytokines and chemokines in semen of both HIV-infected and uninfected
      men, and another seven further enriched in infected individuals. The enrichment
      of cytokines involved in innate immunity in the seminal tract, complemented with
      chemokines in infected men, creates an environment conducive to T cell activation
      and viral replication. These studies define different relationships between virus
      in blood and semen that can significantly alter the composition of the viral
      population at the source that is most proximal to the transmitted virus.

PMID- 20808903
TI  - A subset of replication proteins enhances origin recognition and lytic
      replication by the Epstein-Barr virus ZEBRA protein.
AB  - ZEBRA is a site-specific DNA binding protein that functions as a transcriptional
      activator and as an origin binding protein. Both activities require that ZEBRA
      recognizes DNA motifs that are scattered along the viral genome. The mechanism by
      which ZEBRA discriminates between the origin of lytic replication and promoters
      of EBV early genes is not well understood. We explored the hypothesis that
      activation of replication requires stronger association between ZEBRA and DNA
      than does transcription. A ZEBRA mutant, Z(S173A), at a phosphorylation site and
      three point mutants in the DNA recognition domain of ZEBRA, namely Z(Y180E),
      Z(R187K) and Z(K188A), were similarly deficient at activating lytic DNA
      replication and expression of late gene expression but were competent to activate
      transcription of viral early lytic genes. These mutants all exhibited reduced
      capacity to interact with DNA as assessed by EMSA, ChIP and an in vivo
      biotinylated DNA pull-down assay. Over-expression of three virally encoded
      replication proteins, namely the primase (BSLF1), the single-stranded DNA-binding
      protein (BALF2) and the DNA polymerase processivity factor (BMRF1), partially
      rescued the replication defect in these mutants and enhanced ZEBRA's interaction
      with oriLyt. The findings demonstrate a functional role of replication proteins
      in stabilizing the association of ZEBRA with viral DNA. Enhanced binding of ZEBRA
      to oriLyt is crucial for lytic viral DNA replication.

PMID- 20808904
TI  - Routine laboratory results and thirty day and one-year mortality risk following
      hospitalization with acute decompensated heart failure.
AB  - INTRODUCTION: Several blood tests are performed uniformly in patients
      hospitalized with acute decompensated heart failure and are predictive of the
      outcomes: complete blood count, electrolytes, renal function, glucose, albumin
      and uric acid. We sought to evaluate the relationship between routine admission
      laboratory tests results, patient characteristics and 30-day and one-year
      mortality of patients admitted for decompensated heart failure and to construct a
      simple mortality prediction tool. METHODS: A retrospective population based
      study. Data from seven tertiary hospitals on all admissions with a principal
      diagnosis of heart failure during the years 2002-2005 throughout Israel were
      captured. RESULTS: 8,246 patients were included in the study cohort. Thirty day
      mortality rate was 8.5% (701 patients) and one-year mortality rate was 28.7%
      (2,365 patients). Addition of five routine laboratory tests results (albumin,
      sodium, blood urea, uric acid and WBC) to a set of clinical and demographic
      characteristics improved c-statistics from 0.76 to 0.81 for 30-days and from 0.72
      to 0.76 for one-year mortality prediction (both p-values <0.0001). Three
      dichotomized abnormal laboratory results with highest odds ratio for one-year
      mortality (hypoalbuminaemia, hyponatremia and elevated blood urea) were used to
      construct a simple prediction score, capable of discriminating from 1.1% to 21.4%
      in 30-day and from 11.6% to 55.6% in one-year mortality rates between patients
      with a score of 0 (1,477 patients) vs. score of 3 (544 patients). DISCUSSION: A
      small set of abnormal routine laboratory results upon admission can risk-stratify
      and independently predict 30-day and one-year mortality in patients hospitalized
      with acute decompensated heart failure.

PMID- 20808905
TI  - Evolutionary systems biology of amino acid biosynthetic cost in yeast.
AB  - Every protein has a biosynthetic cost to the cell based on the synthesis of its
      constituent amino acids. In order to optimise growth and reproduction, natural
      selection is expected, where possible, to favour the use of proteins whose
      constituents are cheaper to produce, as reduced biosynthetic cost may confer a
      fitness advantage to the organism. Quantifying the cost of amino acid
      biosynthesis presents challenges, since energetic requirements may change across
      different cellular and environmental conditions. We developed a systems biology
      approach to estimate the cost of amino acid synthesis based on genome-scale
      metabolic models and investigated the effects of the cost of amino acid synthesis
      on Saccharomyces cerevisiae gene expression and protein evolution. First, we used
      our two new and six previously reported measures of amino acid cost in
      conjunction with codon usage bias, tRNA gene number and atomic composition to
      identify which of these factors best predict transcript and protein levels.
      Second, we compared amino acid cost with rates of amino acid substitution across
      four species in the genus Saccharomyces. Regardless of which cost measure is
      used, amino acid biosynthetic cost is weakly associated with transcript and
      protein levels. In contrast, we find that biosynthetic cost and amino acid
      substitution rates show a negative correlation, but for only a subset of cost
      measures. In the economy of the yeast cell, we find that the cost of amino acid
      synthesis plays a limited role in shaping transcript and protein expression
      levels compared to that of translational optimisation. Biosynthetic cost does,
      however, appear to affect rates of amino acid evolution in Saccharomyces,
      suggesting that expensive amino acids may only be used when they have specific
      structural or functional roles in protein sequences. However, as there appears to
      be no single currency to compute the cost of amino acid synthesis across all
      cellular and environmental conditions, we conclude that a systems approach is
      necessary to unravel the full effects of amino acid biosynthetic cost in complex
      biological systems.

PMID- 20808906
TI  - Polyphosphate kinase 2: a novel determinant of stress responses and pathogenesis
      in Campylobacter jejuni.
AB  - BACKGROUND: Inorganic polyphosphate (poly P) plays an important role in stress
      tolerance and virulence in many bacteria. PPK1 is the principal enzyme involved
      in poly P synthesis, while PPK2 uses poly P to generate GTP, a signaling molecule
      that serves as an alternative energy source and a precursor for various
      physiological processes. Campylobacter jejuni, an important cause of foodborne
      gastroenteritis in humans, possesses homologs of both ppk1 and ppk2. ppk1 has
      been previously shown to impact the pathobiology of C. jejuni.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, we demonstrate for the first time that the
      deletion of ppk2 in C. jejuni resulted in a significant decrease in poly P
      dependent GTP synthesis, while displaying an increased intracellular ATP:GTP
      ratio. The Deltappk2 mutant exhibited a significant survival defect under
      osmotic, nutrient, aerobic, and antimicrobial stresses and displayed an enhanced
      ability to form static biofilms. However, the Deltappk2 mutant was not defective
      in poly P and ppGpp synthesis suggesting that PPK2-mediated stress tolerance is
      not ppGpp-mediated. Importantly, the Deltappk2 mutant was significantly
      attenuated in invasion and intracellular survival within human intestinal
      epithelial cells as well as in chicken colonization. CONCLUSIONS/SIGNIFICANCE:
      Taken together, we have highlighted the role of PPK2 as a novel pathogenicity
      determinant that is critical for C. jejuni survival, adaptation, and persistence
      in the host environments. PPK2 is absent in humans and animals; therefore, can
      serve as a novel target for therapeutic intervention of C. jejuni infections.

PMID- 20808907
TI  - Inter-brain synchronization during social interaction.
AB  - During social interaction, both participants are continuously active, each
      modifying their own actions in response to the continuously changing actions of
      the partner. This continuous mutual adaptation results in interactional synchrony
      to which both members contribute. Freely exchanging the role of imitator and
      model is a well-framed example of interactional synchrony resulting from a mutual
      behavioral negotiation. How the participants' brain activity underlies this
      process is currently a question that hyperscanning recordings allow us to
      explore. In particular, it remains largely unknown to what extent oscillatory
      synchronization could emerge between two brains during social interaction. To
      explore this issue, 18 participants paired as 9 dyads were recorded with dual
      video and dual-EEG setups while they were engaged in spontaneous imitation of
      hand movements. We measured interactional synchrony and the turn-taking between
      model and imitator. We discovered by the use of nonlinear techniques that states
      of interactional synchrony correlate with the emergence of an interbrain
      synchronizing network in the alpha-mu band between the right centroparietal
      regions. These regions have been suggested to play a pivotal role in social
      interaction. Here, they acted symmetrically as key functional hubs in the
      interindividual brainweb. Additionally, neural synchronization became
      asymmetrical in the higher frequency bands possibly reflecting a top-down
      modulation of the roles of model and imitator in the ongoing interaction.

PMID- 20808908
TI  - Interactions between Global Health Initiatives and country health systems: the
      case of a neglected tropical diseases control program in Mali.
AB  - BACKGROUND: Recently, a number of Global Health Initiatives (GHI) have been
      created to address single disease issues in low-income countries, such as
      poliomyelitis, trachoma, neonatal tetanus, etc.. Empirical evidence on the
      effects of such GHIs on local health systems remains scarce. This paper explores
      positive and negative effects of the Integrated Neglected Tropical Disease (NTD)
      Control Initiative, consisting in mass preventive chemotherapy for five targeted
      NTDs, on Mali's health system where it was first implemented in 2007. METHODS AND
      FINDINGS: Campaign processes and interactions with the health system were
      assessed through participant observation in two rural districts (8 health centres
      each). Information was complemented by interviews with key informants, website
      search and literature review. Preliminary results were validated during feedback
      sessions with Malian authorities from national, regional and district levels. We
      present positive and negative effects of the NTD campaign on the health system
      using the WHO framework of analysis based on six interrelated elements: health
      service delivery, health workforce, health information system, drug procurement
      system, financing and governance. At point of delivery, campaign-related workload
      severely interfered with routine care delivery which was cut down or totally
      interrupted during the campaign, as nurses were absent from their health centre
      for campaign-related activities. Only 2 of the 16 health centres, characterized
      by a qualified, stable and motivated workforce, were able to keep routine
      services running and to use the campaign as an opportunity for quality
      improvement. Increased workload was compensated by allowances, which
      significantly improved staff income, but also contributed to divert attention
      away from core routine activities. While the campaign increased the availability
      of NTD drugs at country level, parallel systems for drug supply and evaluation
      requested extra efforts burdening local health systems. The campaign budget
      barely financed institutional strengthening. Finally, though the initiative
      rested at least partially on national structures, pressures to absorb donated
      drugs and reach short-term coverage results contributed to distract energies away
      from other priorities, including overall health systems strengthening.
      CONCLUSIONS: Our study indicates that positive synergies between disease specific
      interventions and nontargeted health services are more likely to occur in robust
      health services and systems. Disease-specific interventions implemented as
      parallel activities in fragile health services may further weaken their
      responsiveness to community needs, especially when several GHIs operate
      simultaneously. Health system strengthening will not result from the sum of
      selective global interventions but requires a comprehensive approach.

PMID- 20808909
TI  - Rhabdastrellic acid-A induced autophagy-associated cell death through blocking
      Akt pathway in human cancer cells.
AB  - BACKGROUND: Autophagy is an evolutionarily conserved protein degradation pathway.
      A defect in autophagy may contribute to tumorigenesis. Autophagy inducers could
      have a potential function in tumor prevention and treatment.
      METHODOLOGY/PRINCIPAL FINDINGS: Our results showed that Rhabdastrellic acid-A, an
      isomalabaricane triterpenoid isolated from the sponge Rhabdastrella
      globostellata, inhibited proliferation of human cancer cell lines Hep3B and A549
      and induced caspase-independent cell death in both the cell lines. Further
      investigation showed that Rhabdastrellic acid-A induced autophagy of cancer cells
      determined by YFP-LC3 punctation and increased LC3-II. The pretreatment with
      autophagy inhibitor 3-MA inhibited Rhabdastrellic acid-A-induced cell death.
      Knockdown of autophagy-related gene Atg5 inhibited Rhabdastrellic acid-A-induced
      cell death in A549 cells. Also, phospho-Akt and its downstream targets
      significantly decreased after treatment with Rhabdastrellic acid-A in both cancer
      cell lines. Transfection of constitutive active Akt plasmid abrogated autophagy
      and cell death induced by Rhabdastrellic acid-A. CONCLUSIONS/SIGNIFICANCE: These
      results suggest that Rhabdastrellic acid-A could induce autophagy-associated cell
      death through blocking Akt pathway in cancer cells. It also provides the evidence
      that Rhabdastrellic acid-A deserves further investigation as a potential
      anticancer or cancer preventive agent.

PMID- 20808910
TI  - Targeting trachoma control through risk mapping: the example of Southern Sudan.
AB  - BACKGROUND: Trachoma is a major cause of blindness in Southern Sudan. Its
      distribution has only been partially established and many communities in need of
      intervention have therefore not been identified or targeted. The present study
      aimed to develop a tool to improve targeting of survey and control activities.
      METHODS/PRINCIPAL FINDINGS: A national trachoma risk map was developed using
      Bayesian geostatistics models, incorporating trachoma prevalence data from 112
      geo-referenced communities surveyed between 2001 and 2009. Logistic regression
      models were developed using active trachoma (trachomatous inflammation follicular
      and/or trachomatous inflammation intense) in 6345 children aged 1-9 years as the
      outcome, and incorporating fixed effects for age, long-term average rainfall
      (interpolated from weather station data) and land cover (i.e. vegetation type,
      derived from satellite remote sensing), as well as geostatistical random effects
      describing spatial clustering of trachoma. The model predicted the west of the
      country to be at no or low trachoma risk. Trachoma clusters in the central,
      northern and eastern areas had a radius of 8 km after accounting for the fixed
      effects. CONCLUSION: In Southern Sudan, large-scale spatial variation in the risk
      of active trachoma infection is associated with aridity. Spatial prediction has
      identified likely high-risk areas to be prioritized for more data collection,
      potentially to be followed by intervention.

PMID- 20808911
TI  - A transposon in Comt generates mRNA variants and causes widespread expression and
      behavioral differences among mice.
AB  - BACKGROUND: Catechol-O-methyltransferase (COMT) is a key enzyme responsible for
      the degradation of dopamine and norepinephrine. COMT activity influences
      cognitive and emotional states in humans and aggression and drug responses in
      mice. This study identifies the key sequence variant that leads to differences in
      Comt mRNA and protein levels among mice, and that modulates synaptic function and
      pharmacological and behavioral traits. METHODOLOGY/PRINCIPAL FINDINGS: We
      examined Comt expression in multiple tissues in over 100 diverse strains and
      several genetic crosses. Differences in expression map back to Comt and are
      generated by a 230 nt insertion of a B2 short interspersed element (B2 SINE) in
      the proximal 3' UTR of Comt in C57BL/6J. This transposon introduces a premature
      polyadenylation signal and creates a short 3' UTR isoform. The B2 SINE is shared
      by a subset of strains, including C57BL/6J, A/J, BALB/cByJ, and AKR/J, but is
      absent in others, including DBA/2J, FVB/NJ, SJL/J, and wild subspecies. The short
      isoform is associated with increased protein expression in prefrontal cortex and
      hippocampus relative to the longer ancestral isoform. The Comt variant causes
      downstream differences in the expression of genes involved in synaptic function,
      and also modulates phenotypes such as dopamine D1 and D2 receptor binding and
      pharmacological responses to haloperidol. CONCLUSIONS/SIGNIFICANCE: We have
      precisely defined the B2 SINE as the source of variation in Comt and demonstrated
      that a transposon in a 3' UTR can alter mRNA isoform use and modulate behavior.
      The recent fixation of the variant in a subset of strains may have contributed to
      the rapid divergence of inbred strains.

PMID- 20808912
TI  - Summer hot snaps and winter conditions: modelling white syndrome outbreaks on
      Great Barrier Reef corals.
AB  - Coral reefs are under increasing pressure in a changing climate, one such threat
      being more frequent and destructive outbreaks of coral diseases. Thermal stress
      from rising temperatures has been implicated as a causal factor in disease
      outbreaks observed on the Great Barrier Reef, Australia, and elsewhere in the
      world. Here, we examine seasonal effects of satellite-derived temperature on the
      abundance of coral diseases known as white syndromes on the Great Barrier Reef,
      considering both warm stress during summer and deviations from mean temperatures
      during the preceding winter. We found a high correlation (r(2) = 0.953) between
      summer warm thermal anomalies (Hot Snap) and disease abundance during outbreak
      events. Inclusion of thermal conditions during the preceding winter revealed that
      a significant reduction in disease outbreaks occurred following especially cold
      winters (Cold Snap), potentially related to a reduction in pathogen loading.
      Furthermore, mild winters (i.e., neither excessively cool nor warm) frequently
      preceded disease outbreaks. In contrast, disease outbreaks did not typically
      occur following warm winters, potentially because of increased disease resistance
      of the coral host. Understanding the balance between the effects of warm and cold
      winters on disease outbreak will be important in a warming climate. Combining the
      influence of winter and summer thermal effects resulted in an algorithm that
      yields both a Seasonal Outlook of disease risk at the conclusion of winter and
      near real-time monitoring of Outbreak Risk during summer. This satellite-derived
      system can provide coral reef managers with an assessment of risk three-to-six
      months in advance of the summer season that can then be refined using near-real
      time summer observations. This system can enhance the capacity of managers to
      prepare for and respond to possible disease outbreaks and focus research efforts
      to increase understanding of environmental impacts on coral disease in this era
      of rapidly changing climate.

PMID- 20808913
TI  - Bovine tuberculosis at the wildlife-livestock-human interface in Hamer Woreda,
      South Omo, Southern Ethiopia.
AB  - Bovine tuberculosis (BTB) is endemic in cattle in the Ethiopian Highlands but no
      studies have been done so far in pastoralists in South Omo. This study assessed
      the prevalence of bovine tuberculosis (BTB) at an intensive interface of
      livestock, wildlife and pastoralists in Hamer Woreda (South Omo), Ethiopia. A
      cross-sectional survey including a comparative intradermal skin testing (CIDT)
      was conducted in 499 zebu cattle and 186 goats in 12 settlements. Sputum samples
      from 26 symptomatic livestock owners were cultured for TB. Fifty-one wildlife
      samples from 13 different species were also collected in the same area and tested
      with serological (lateral flow assay) and bacteriological (culture of lymph
      nodes) techniques. Individual BTB prevalence in cattle was 0.8% (CI: 0.3%-2%)
      with the >4 mm cut-off and 3.4% (CI: 2.1%-5.4%) with the >2 mm cut-off. Herd
      prevalence was 33.3% and 83% when using the >4 and the >2 mm cut-off
      respectively. There was no correlation between age, sex, body condition and
      positive reactors upon univariate analysis. None of the goats were reactors for
      BTB. Acid fast bacilli (AFB) were detected in 50% of the wildlife cultures, 79.2%
      of which were identified as Mycobacterium terrae complex. No M. bovis was
      detected. Twenty-seven percent of tested wildlife were sero-positive. Four sputum
      cultures (15.4%) yielded AFB positive colonies among which one was M.
      tuberculosis and 3 non-tuberculous mycobacteria (NTM). The prevalence of M. avium
      complex (MAC) was 4.2% in wildlife, 2.5% in cattle and 0.5% in goats. In
      conclusion, individual BTB prevalence was low, but herd prevalence high in cattle
      and BTB was not detected in goats, wildlife and humans despite an intensive
      contact interface. On the contrary, NTMs were highly prevalent and some
      Mycobacterium spp were more prevalent in specific species. The role of NTMs in
      livestock and co-infection with BTB need further research.

PMID- 20808914
TI  - Spatial regulation of membrane fusion controlled by modification of
      phosphoinositides.
AB  - Membrane fusion plays a central role in many cell processes from vesicular
      transport to nuclear envelope reconstitution at mitosis but the mechanisms that
      underlie fusion of natural membranes are not well understood. Studies with
      synthetic membranes and theoretical considerations indicate that accumulation of
      lipids characterised by negative curvature such as diacylglycerol (DAG)
      facilitate fusion. However, the specific role of lipids in membrane fusion of
      natural membranes is not well established. Nuclear envelope (NE) assembly was
      used as a model for membrane fusion. A natural membrane population highly
      enriched in the enzyme and substrate needed to produce DAG has been isolated and
      is required for fusions leading to nuclear envelope formation, although it
      contributes only a small amount of the membrane eventually incorporated into the
      NE. It was postulated to initiate and regulate membrane fusion. Here we use a
      multidisciplinary approach including subcellular membrane purification,
      fluorescence spectroscopy and Forster resonance energy transfer (FRET)/two-photon
      fluorescence lifetime imaging microscopy (FLIM) to demonstrate that initiation of
      vesicle fusion arises from two unique sites where these vesicles bind to
      chromatin. Fusion is subsequently propagated to the endoplasmic reticulum-derived
      membranes that make up the bulk of the NE to ultimately enclose the chromatin. We
      show how initiation of multiple vesicle fusions can be controlled by localised
      production of DAG and propagated bidirectionally. Phospholipase C (PLCgamma), GTP
      hydrolysis and (phosphatidylinsositol-(4,5)-bisphosphate (PtdIns(4,5)P(2)) are
      required for the latter process. We discuss the general implications of membrane
      fusion regulation and spatial control utilising such a mechanism.

PMID- 20808915
TI  - The use of P63 immunohistochemistry for the identification of squamous cell
      carcinoma of the lung.
AB  - INTRODUCTION: While some targeted agents should not be used in squamous cell
      carcinomas (SCCs), other agents might preferably target SCCs. In a previous
      microarray study, one of the top differentially expressed genes between
      adenocarcinomas (ACs) and SCCs is P63. It is a well-known marker of squamous
      differentiation, but surprisingly, its expression is not widely used for this
      purpose. Our goals in this study were (1) to further confirm our microarray data,
      (2) to analize the value of P63 immunohistochemistry (IHC) in reducing the number
      of large cell carcinoma (LCC) diagnoses in surgical specimens, and (3) to
      investigate the potential of P63 IHC to minimize the proportion of "carcinoma NOS
      (not otherwise specified)" in a prospective series of small tumor samples.
      METHODS: With these goals in mind, we studied (1) a tissue-microarray comprising
      33 ACs and 99 SCCs on which we performed P63 IHC, (2) a series of 20 surgically
      resected LCCs studied for P63 and TTF-1 IHC, and (3) a prospective cohort of 66
      small thoracic samples, including 32 carcinoma NOS, that were further classified
      by the result of P63 and TTF-1 IHC. RESULTS: The results in the three independent
      cohorts were as follows: (1) P63 IHC was differentially expressed in SCCs when
      compared to ACs (p<0.0001); (2) half of the 20 (50%) LCCs were positive for P63
      and were reclassified as SCCs; and (3) all P63 positive cases (34%) were
      diagnosed as SCCs. CONCLUSIONS: P63 IHC is useful for the identification of lung
      SCCs.

PMID- 20808916
TI  - Linking in vitro and in vivo survival of clinical Leishmania donovani strains.
AB  - BACKGROUND: Leishmania donovani is an intracellular protozoan parasite that
      causes a lethal systemic disease, visceral leishmaniasis (VL), and is transmitted
      between mammalian hosts by phlebotomine sandflies. Leishmania expertly survives
      in these 'hostile' environments with a unique redox system protecting against
      oxidative damage, and host manipulation skills suppressing oxidative outbursts of
      the mammalian host. Treating patients imposes an additional stress on the
      parasite and sodium stibogluconate (SSG) was used for over 70 years in the Indian
      subcontinent. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated whether the survival
      capacity of clinical L. donovani isolates varies significantly at different
      stages of their life cycle by comparing proliferation, oxidative stress tolerance
      and infection capacity of 3 Nepalese L. donovani strains in several in vitro and
      in vivo models. In general, the two strains that were resistant to SSG, a stress
      encountered in patients, attained stationary phase at a higher parasite density,
      contained a higher amount of metacyclic parasites and had a greater capacity to
      cause in vivo infection in mice compared to the SSG-sensitive strain.
      CONCLUSIONS/SIGNIFICANCE: The 2 SSG-resistant strains had superior survival
      skills as promastigotes and as amastigotes compared to the SSG-sensitive strain.
      These results could indicate that Leishmania parasites adapting successfully to
      antimonial drug pressure acquire an overall increased fitness, which stands in
      contrast to what is found for other organisms, where drug resistance is usually
      linked to a fitness cost. Further validation experiments are under way to verify
      this hypothesis.

PMID- 20808917
TI  - Filamin a binds to CCR2B and regulates its internalization.
AB  - The chemokine (C-C motif) receptor 2B (CCR2B) is one of the two isoforms of the
      receptor for monocyte chemoattractant protein-1 (CCL2), the major chemoattractant
      for monocytes, involved in an array of chronic inflammatory diseases. Employing
      the yeast two-hybrid system, we identified the actin-binding protein filamin A
      (FLNa) as a protein that associates with the carboxyl-terminal tail of CCR2B. Co
      immunoprecipitation experiments and in vitro pull down assays demonstrated that
      FLNa binds constitutively to CCR2B. The colocalization of endogenous CCR2B and
      filamin A was detected at the surface and in internalized vesicles of THP-1
      cells. In addition, CCR2B and FLNa were colocalized in lamellipodia structures of
      CCR2B-expressing A7 cells. Expression of the receptor in filamin-deficient M2
      cells together with siRNA experiments knocking down FLNa in HEK293 cells,
      demonstrated that lack of FLNa delays the internalization of the receptor.
      Furthermore, depletion of FLNa in THP-1 monocytes by RNA interference reduced the
      migration of cells in response to MCP-1. Therefore, FLNa emerges as an important
      protein for controlling the internalization and spatial localization of the CCR2B
      receptor in different dynamic membrane structures.

PMID- 20808918
TI  - Accumulative difference image protocol for particle tracking in fluorescence
      microscopy tested in mouse lymphonodes.
AB  - The basic research in cell biology and in medical sciences makes large use of
      imaging tools mainly based on confocal fluorescence and, more recently, on non
      linear excitation microscopy. Substantially the aim is the recognition of
      selected targets in the image and their tracking in time. We have developed a
      particle tracking algorithm optimized for low signal/noise images with a minimum
      set of requirements on the target size and with no a priori knowledge of the type
      of motion. The image segmentation, based on a combination of size sensitive
      filters, does not rely on edge detection and is tailored for targets acquired at
      low resolution as in most of the in-vivo studies. The particle tracking is
      performed by building, from a stack of Accumulative Difference Images, a single
      2D image in which the motion of the whole set of the particles is coded in time
      by a color level. This algorithm, tested here on solid-lipid nanoparticles
      diffusing within cells and on lymphocytes diffusing in lymphonodes, appears to be
      particularly useful for the cellular and the in-vivo microscopy image processing
      in which few a priori assumption on the type, the extent and the variability of
      particle motions, can be done.

PMID- 20808919
TI  - Role of mast cells in inflammatory bowel disease and inflammation-associated
      colorectal neoplasia in IL-10-deficient mice.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is hypothesized to result from
      stimulation of immune responses against resident intestinal bacteria within a
      genetically susceptible host. Mast cells may play a critical role in IBD
      pathogenesis, since they are typically located just beneath the intestinal
      mucosal barrier and can be activated by bacterial antigens. METHODOLOGY/PRINCIPAL
      FINDINGS: This study investigated effects of mast cells on inflammation and
      associated neoplasia in IBD-susceptible interleukin (IL)-10-deficient mice with
      and without mast cells. IL-10-deficient mast cells produced more pro-inflammatory
      cytokines in vitro both constitutively and when triggered, compared with wild
      type mast cells. However despite this enhanced in vitro response, mast cell
      sufficient Il10(-/-) mice actually had decreased cecal expression of tumor
      necrosis factor (TNF) and interferon (IFN)-gamma mRNA, suggesting that mast cells
      regulate inflammation in vivo. Mast cell deficiency predisposed Il10(-/-) mice to
      the development of spontaneous colitis and resulted in increased intestinal
      permeability in vivo that preceded the development of colon inflammation.
      However, mast cell deficiency did not affect the severity of IBD triggered by non
      steroidal anti-inflammatory agents (NSAID) exposure or helicobacter infection
      that also affect intestinal permeability. CONCLUSIONS/SIGNIFICANCE: Mast cells
      thus appear to have a primarily protective role within the colonic
      microenvironment by enhancing the efficacy of the mucosal barrier. In addition,
      although mast cells were previously implicated in progression of sporadic colon
      cancers, mast cells did not affect the incidence or severity of colonic neoplasia
      in this inflammation-associated model.

PMID- 20808920
TI  - Evaluation of the house fly Musca domestica as a mechanical vector for an
      anthrax.
AB  - Anthrax is a disease of human beings and animals caused by the encapsulated,
      spore-forming, Bacillus anthracis. The potential role of insects in the spread of
      B. anthracis to humans and domestic animals during an anthrax outbreak has been
      confirmed by many studies. Among insect vectors, the house fly Musca domestica is
      considered a potential agent for disease transmission. In this study, laboratory
      bred specimens of Musca domestica were infected by feeding on anthrax-infected
      rabbit carcass or anthrax contaminated blood, and the presence of anthrax spores
      in their spots (faeces and vomitus) was microbiologically monitored. It was also
      evaluated if the anthrax spores were able to germinate and replicate in the gut
      content of insects. These results confirmed the role of insects in spreading
      anthrax infection. This role, although not major, given the huge size of fly
      populations often associated with anthrax epidemics in domestic animals, cannot
      be neglected from an epidemiological point of view and suggest that fly control
      should be considered as part of anthrax control programs.

PMID- 20808921
TI  - Expansion of cord blood CD34 cells in presence of zVADfmk and zLLYfmk improved
      their in vitro functionality and in vivo engraftment in NOD/SCID mouse.
AB  - BACKGROUND: Cord blood (CB) is a promising source for hematopoietic stem cell
      transplantations. The limitation of cell dose associated with this source has
      prompted the ex vivo expansion of hematopoietic stem and progenitor cells
      (HSPCs). However, the expansion procedure is known to exhaust the stem cell pool
      causing cellular defects that promote apoptosis and disrupt homing to the bone
      marrow. The role of apoptotic machinery in the regulation of stem cell
      compartment has been speculated in mouse hematopoietic and embryonic systems. We
      have consistently observed an increase in apoptosis in the cord blood derived
      CD34(+) cells cultured with cytokines compared to their freshly isolated
      counterpart. The present study was undertaken to assess whether pharmacological
      inhibition of apoptosis could improve the outcome of expansion.
      METHODOLOGY/PRINCIPAL FINDINGS: CB CD34(+) cells were expanded with cytokines in
      the presence or absence of cell permeable inhibitors of caspases and calpains;
      zVADfmk and zLLYfmk respectively. A novel role of apoptotic protease inhibitors
      was observed in increasing the CD34(+) cell content of the graft during ex vivo
      expansion. This was further reflected in improved in vitro functional aspects of
      the HSPCs; a higher clonogenicity and long term culture initiating potential.
      These cells sustained superior long term engraftment and an efficient
      regeneration of major lympho-myeloid lineages in the bone marrow of NOD/SCID
      mouse compared to the cells expanded with growth factors alone.
      CONCLUSION/SIGNIFICANCE: Our data show that, use of either zVADfmk or zLLYfmk in
      the culture medium improves expansion of CD34(+) cells. The strategy protects
      stem cell pool and committed progenitors, and improves their in vitro
      functionality and in vivo engraftment. This observation may complement the
      existing protocols used in the manipulation of hematopoietic cells for
      therapeutic purposes. These findings may have an impact in the CB transplant
      procedures involving a combined infusion of unmanipulated and expanded grafts.

PMID- 20808922
TI  - Hybrid models identified a 12-gene signature for lung cancer prognosis and
      chemoresponse prediction.
AB  - BACKGROUND: Lung cancer remains the leading cause of cancer-related deaths
      worldwide. The recurrence rate ranges from 35-50% among early stage non-small
      cell lung cancer patients. To date, there is no fully-validated and clinically
      applied prognostic gene signature for personalized treatment.
      METHODOLOGY/PRINCIPAL FINDINGS: From genome-wide mRNA expression profiles
      generated on 256 lung adenocarcinoma patients, a 12-gene signature was identified
      using combinatorial gene selection methods, and a risk score algorithm was
      developed with Naive Bayes. The 12-gene model generates significant patient
      stratification in the training cohort HLM & UM (n = 256; log-rank P = 6.96e-7)
      and two independent validation sets, MSK (n = 104; log-rank P = 9.88e-4) and DFCI
      (n = 82; log-rank P = 2.57e-4), using Kaplan-Meier analyses. This gene signature
      also stratifies stage I and IB lung adenocarcinoma patients into two distinct
      survival groups (log-rank P<0.04). The 12-gene risk score is more significant
      (hazard ratio = 4.19, 95% CI: [2.08, 8.46]) than other commonly used clinical
      factors except tumor stage (III vs. I) in multivariate Cox analyses. The 12-gene
      model is more accurate than previously published lung cancer gene signatures on
      the same datasets. Furthermore, this signature accurately predicts
      chemoresistance/chemosensitivity to Cisplatin, Carboplatin, Paclitaxel,
      Etoposide, Erlotinib, and Gefitinib in NCI-60 cancer cell lines (P<0.017). The
      identified 12 genes exhibit curated interactions with major lung cancer signaling
      hallmarks in functional pathway analysis. The expression patterns of the
      signature genes have been confirmed in RT-PCR analyses of independent tumor
      samples. CONCLUSIONS/SIGNIFICANCE: The results demonstrate the clinical utility
      of the identified gene signature in prognostic categorization. With this 12-gene
      risk score algorithm, early stage patients at high risk for tumor recurrence
      could be identified for adjuvant chemotherapy; whereas stage I and II patients at
      low risk could be spared the toxic side effects of chemotherapeutic drugs.

PMID- 20808923
TI  - Cost effectiveness of seasonal intermittent preventive treatment using
      amodiaquine & artesunate or sulphadoxine-pyrimethamine in Ghanaian children.
AB  - BACKGROUND: Intermittent preventive treatment for malaria in children (IPTc)
      involves the administration of a full course of an anti-malarial treatment to
      children under 5 years old at specified time points regardless of whether or not
      they are known to be infected, in areas where malaria transmission is seasonal.
      It is important to determine the costs associated with IPTc delivery via
      community based volunteers and also the potential savings to health care
      providers and caretakers due to malaria episodes averted as a consequence of
      IPTc. METHODS: Two thousand four hundred and fifty-one children aged 3-59 months
      were randomly allocated to four groups to receive: three days of artesunate plus
      amodiaquine (AS+AQ) monthly, three days of AS+AQ bimonthly, one dose of
      sulphadoxine-pyrimethamine (SP) bi-monthly or placebo. This paper focuses on
      incremental cost effectiveness ratios (ICERs) of the three IPTc drug regimens as
      delivered by community based volunteers (CBV) in Hohoe, Ghana compared to current
      practice, i.e. case management in the absence of IPTc. Financial and economic
      costs from the publicly funded health system perspective are presented. Treatment
      costs borne by patients and their caretakers are also estimated to present
      societal costs. The costs and effects of IPTc during the intervention period were
      considered with and without a one year follow up. Probabilistic sensitivity
      analysis was undertaken to account for uncertainty. RESULTS: Economic costs per
      child receiving at least the first dose of each course of IPTc show SP bimonthly,
      at US$8.19, is the cheapest to deliver, followed by AS+AQ bimonthly at US$10.67
      and then by AS+AQ monthly at US$14.79. Training, drug delivery and supervision
      accounted for approximately 20-30% each of total unit costs. During the
      intervention period AS & AQ monthly was the most cost effective IPTc drug regimen
      at US$67.77 (61.71-74.75, CI 95%) per malaria case averted based on intervention
      costs only, US$64.93 (58.92-71.92, CI 95%) per malaria case averted once the
      provider cost savings are included and US$61.00 (54.98, 67.99, CI 95%) when
      direct household cost savings are also taken into account. SP bimonthly was
      US$105.35 (75.01-157.31, CI 95%) and AS & AQ bimonthly US$211.80 (127.05-399.14,
      CI 95%) per malaria case averted based on intervention costs only. The incidence
      of malaria in the post intervention period was higher in children who were <1
      year old when they received AS+AQ monthly compared to the placebo group leading
      to higher cost effectiveness ratios when one year follow up is included. The cost
      per child enrolled fell considerably when modelled to district level as compared
      to those encountered under trial conditions. CONCLUSIONS: We demonstrate how cost
      effective IPTc is using three different drug regimens and the possibilities for
      reducing costs further if the intervention was to be scaled up to the district
      level. The need for effective training, drug delivery channels and supervision to
      support a strong network of community based volunteers is emphasised.

PMID- 20808924
TI  - An oligopeptide transporter of Mycobacterium tuberculosis regulates cytokine
      release and apoptosis of infected macrophages.
AB  - BACKGROUND: The Mycobacterium tuberculosis genome encodes two peptide
      transporters encoded by Rv3665c-Rv3662c and Rv1280c-Rv1283c. Both belong to the
      family of ABC transporters containing two nucleotide-binding subunits, two
      integral membrane proteins and one substrate-binding polypeptide. However, little
      is known about their functions in M. tuberculosis. Here we report functional
      characterization of the Rv1280c-Rv1283c-encoded transporter and its substrate
      binding polypeptide OppA(MTB). METHODOLOGY/PRINCIPAL FINDINGS: OppA(MTB) was
      capable of binding the tripeptide glutathione and the nonapeptide bradykinin,
      indicative of a somewhat broad substrate specificity. Amino acid residues G109,
      N110, N230, D494 and F496, situated at the interface between domains I and III of
      OppA, were required for optimal peptide binding. Complementaton of an oppA
      knockout mutant of M. smegmatis with OppA(MTB) confirmed the role of this
      transporter in importing glutathione and the importance of the aforesaid amino
      acid residues in peptide transport. Interestingly, this transporter regulated the
      ability of M. tuberculosis to lower glutathione levels in infected compared to
      uninfected macrophages. This ability was partly offset by inactivation of oppD.
      Concomitantly, inactivation of oppD was associated with lowered levels of methyl
      glyoxal in infected macrophages and reduced apoptosis-inducing ability of the
      mutant. The ability to induce the production of the cytokines IL-1beta, IL-6 and
      TNF-alpha was also compromised after inactivation of oppD. CONCLUSIONS: Taken
      together, these studies uncover the novel observations that this peptide
      transporter modulates the innate immune response of macrophages infected with M.
      tuberculosis.

PMID- 20808925
TI  - Extraction of BoNT/A, /B, /E, and /F with a single, high affinity monoclonal
      antibody for detection of botulinum neurotoxin by Endopep-MS.
AB  - Botulinum neurotoxins (BoNTs) are extremely potent toxins that are capable of
      causing respiratory failure leading to long-term intensive care or death. The
      best treatment for botulism includes serotype-specific antitoxins, which are most
      effective when administered early in the course of the intoxication. Early
      confirmation of human exposure to any serotype of BoNT is an important public
      health goal. In previous work, we focused on developing Endopep-MS, a mass
      spectrometry-based endopeptidase method for detecting and differentiating the
      seven serotypes (BoNT/A-G) in buffer and BoNT/A, /B, /E, and /F (the four
      serotypes that commonly affect humans) in clinical samples. We have previously
      reported the success of antibody-capture to purify and concentrate BoNTs from
      complex matrices, such as clinical samples. However, to check for any one of the
      four serotypes of BoNT/A, /B, /E, or /F, each sample is split into 4 aliquots,
      and tested for the specific serotypes separately. The discovery of a unique
      monoclonal antibody that recognizes all four serotypes of BoNT/A, /B, /E and /F
      allows us to perform simultaneous detection of all of them. When applied in
      conjunction with the Endopep-MS assay, the detection limit for each serotype of
      BoNT with this multi-specific monoclonal antibody is similar to that obtained
      when using other serotype-specific antibodies.

PMID- 20808926
TI  - Analysis of vascular development in the hydra sterol biosynthetic mutants of
      Arabidopsis.
AB  - BACKGROUND: The control of vascular tissue development in plants is influenced by
      diverse hormonal signals, but their interactions during this process are not well
      understood. Wild-type sterol profiles are essential for growth, tissue patterning
      and signalling processes in plant development, and are required for regulated
      vascular patterning. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigate the
      roles of sterols in vascular tissue development, through an analysis of the
      Arabidopsis mutants hydra1 and fackel/hydra2, which are defective in the enzymes
      sterol isomerase and sterol C-14 reductase respectively. We show that defective
      vascular patterning in the shoot is associated with ectopic cell divisions.
      Expression of the auxin-regulated AtHB8 homeobox gene is disrupted in mutant
      embryos and seedlings, associated with variably incomplete vascular strand
      formation and duplication of the longitudinal axis. Misexpression of the auxin
      reporter proIAA2ratioGUS and mislocalization of PIN proteins occurs in the
      mutants. Introduction of the ethylene-insensitive ein2 mutation partially rescues
      defective cell division, localization of PIN proteins, and vascular strand
      development. CONCLUSIONS: The results support a model in which sterols are
      required for correct auxin and ethylene crosstalk to regulate PIN localization,
      auxin distribution and AtHB8 expression, necessary for correct vascular
      development.

PMID- 20808927
TI  - bFGF regulates PI3-kinase-Rac1-JNK pathway and promotes fibroblast migration in
      wound healing.
AB  - Fibroblast proliferation and migration play important roles in wound healing.
      bFGF is known to promote both fibroblast proliferation and migration during the
      process of wound healing. However, the signal transduction of bFGF-induced
      fibroblast migration is still unclear, because bFGF can affect both proliferation
      and migration. Herein, we investigated the effect of bFGF on fibroblast migration
      regardless of its effect on fibroblast proliferation. We noticed involvement of
      the small GTPases of the Rho family, PI3-kinase, and JNK. bFGF activated RhoA,
      Rac1, PI3-kinase, and JNK in cultured fibroblasts. Inhibition of RhoA did not
      block bFGF-induced fibroblast migration, whereas inhibition of Rac1, PI3-kinase,
      or JNK blocked the fibroblast migration significantly. PI3-kinase-inhibited cells
      down-regulated the activities of Rac1 and JNK, and Rac1-inhibited cells down
      regulated JNK activity, suggesting that PI3-kinase is upstream of Rac1 and that
      JNK is downstream of Rac1. Thus, we concluded that PI3-kinase, Rac1, and JNK were
      essential for bFGF-induced fibroblast migration, which is a novel pathway of bFGF
      induced cell migration.

PMID- 20808928
TI  - Herpes simplex virus 2 ICP0 mutant viruses are avirulent and immunogenic:
      implications for a genital herpes vaccine.
AB  - Herpes simplex virus 1 (HSV-1) ICP0(-) mutants are interferon-sensitive,
      avirulent, and elicit protective immunity against HSV-1 (Virol J, 2006, 3:44). If
      an ICP0(-) mutant of herpes simplex virus 2 (HSV-2) exhibited similar properties,
      such a virus might be used to vaccinate against genital herpes. The current study
      was initiated to explore this possibility. Several HSV-2 ICP0(-) mutant viruses
      were constructed and evaluated in terms of three parameters: i. interferon
      sensitivity; ii. virulence in mice; and iii. capacity to elicit protective
      immunity against HSV-2. One ICP0(-) mutant virus in particular, HSV-2 0DeltaNLS,
      achieved an optimal balance between avirulence and immunogenicity. HSV-2
      0DeltaNLS was interferon-sensitive in cultured cells. HSV-2 0DeltaNLS replicated
      to low levels in the eyes of inoculated mice, but was rapidly repressed by an
      innate, Stat 1-dependent host immune response. HSV-2 0DeltaNLS failed to spread
      from sites of inoculation, and hence produced only inapparent infections. Mice
      inoculated with HSV-2 0DeltaNLS consistently mounted an HSV-specific IgG antibody
      response, and were consistently protected against lethal challenge with wild-type
      HSV-2. Based on their avirulence and immunogenicity, we propose that HSV-2 ICP0(
      ) mutant viruses merit consideration for their potential to prevent the spread of
      HSV-2 and genital herpes.

PMID- 20808929
TI  - When ears drive hands: the influence of contact sound on reaching to grasp.
AB  - BACKGROUND: Most research on the roles of auditory information and its
      interaction with vision has focused on perceptual performance. Little is known on
      the effects of sound cues on visually-guided hand movements.
      METHODOLOGY/PRINCIPAL FINDINGS: We recorded the sound produced by the fingers
      upon contact as participants grasped stimulus objects which were covered with
      different materials. Then, in a further session the pre-recorded contact sounds
      were delivered to participants via headphones before or following the initiation
      of reach-to-grasp movements towards the stimulus objects. Reach-to-grasp movement
      kinematics were measured under the following conditions: (i) congruent, in which
      the presented contact sound and the contact sound elicited by the to-be-grasped
      stimulus corresponded; (ii) incongruent, in which the presented contact sound was
      different to that generated by the stimulus upon contact; (iii) control, in which
      a synthetic sound, not associated with a real event, was presented. Facilitation
      effects were found for congruent trials; interference effects were found for
      incongruent trials. In a second experiment, the upper and the lower parts of the
      stimulus were covered with different materials. The presented sound was always
      congruent with the material covering either the upper or the lower half of the
      stimulus. Participants consistently placed their fingers on the half of the
      stimulus that corresponded to the presented contact sound.
      CONCLUSIONS/SIGNIFICANCE: Altogether these findings offer a substantial
      contribution to the current debate about the type of object representations
      elicited by auditory stimuli and on the multisensory nature of the sensorimotor
      transformations underlying action.

PMID- 20808930
TI  - Genetic and biochemical characterization of human AP endonuclease 1 mutants
      deficient in nucleotide incision repair activity.
AB  - BACKGROUND: Human apurinic/apyrimidinic endonuclease 1 (APE1) is a key DNA repair
      enzyme involved in both base excision repair (BER) and nucleotide incision repair
      (NIR) pathways. In the BER pathway, APE1 cleaves DNA at AP sites and 3'-blocking
      moieties generated by DNA glycosylases. In the NIR pathway, APE1 incises DNA 5'
      to a number of oxidatively damaged bases. At present, physiological relevance of
      the NIR pathway is fairly well established in E. coli, but has yet to be
      elucidated in human cells. METHODOLOGY/PRINCIPAL FINDING: We identified amino
      acid residues in the APE1 protein that affect its function in either the BER or
      NIR pathway. Biochemical characterization of APE1 carrying single K98A, R185A,
      D308A and double K98A/R185A amino acid substitutions revealed that all mutants
      exhibited greatly reduced NIR and 3'-->5' exonuclease activities, but were
      capable of performing BER functions to some extent. Expression of the APE1
      mutants deficient in the NIR and exonuclease activities reduced the sensitivity
      of AP endonuclease-deficient E. coli xth nfo strain to an alkylating agent,
      methylmethanesulfonate, suggesting that our APE1 mutants are able to repair AP
      sites. Finally, the human NIR pathway was fully reconstituted in vitro using the
      purified APE1, human flap endonuclease 1, DNA polymerase beta and DNA ligase I
      proteins, thus establishing the minimal set of proteins required for a functional
      NIR pathway in human cells. CONCLUSION/SIGNIFICANCE: Taken together, these data
      further substantiate the role of NIR as a distinct and separable function of APE1
      that is essential for processing of potentially lethal oxidative DNA lesions.

PMID- 20808931
TI  - The cost of male aggression and polygyny in California sea lions (Zalophus
      californianus).
AB  - In polygynous mating systems, males often increase their fecundity via aggressive
      defense of mates and/or resources necessary for successful mating. Here we show
      that both male and female reproductive behavior during the breeding season (June
      August) affect female fecundity, a vital rate that is an important determinant of
      population growth rate and viability. By using 4 years of data on behavior and
      demography of California sea lions (Zalophus californianus), we found that male
      behavior and spatial dynamics--aggression and territory size--are significantly
      related to female fecundity. Higher rates of male aggression and larger territory
      sizes were associated with lower estimates of female fecundity within the same
      year. Female aggression was significantly and positively related to fecundity
      both within the same year as the behavior was measured and in the following year.
      These results indicate that while male aggression and defense of territories may
      increase male fecundity, such interactions may cause a reduction in the overall
      population growth rate by lowering female fecundity. Females may attempt to
      offset male-related reductions in female fecundity by increasing their own
      aggression-perhaps to defend pups from incidental injury or mortality. Thus in
      polygynous mating systems, male aggression may increase male fitness at the cost
      of female fitness and overall population viability.

PMID- 20808932
TI  - The impact of mRNA structure on guide RNA targeting in kinetoplastid RNA editing.
AB  - Mitochondrial mRNA editing in Trypanosoma brucei requires the specific
      interaction of a guide RNA with its cognate mRNA. Hundreds of gRNAs are involved
      in the editing process, each needing to target their specific editing domain
      within the target message. We hypothesized that the structure surrounding the
      mRNA target may be a limiting factor and involved in the regulation process. In
      this study, we selected four mRNAs with distinct target structures and
      investigated how sequence and structure affected efficient gRNA targeting. Two of
      the mRNAs, including the ATPase subunit 6 and ND7-550 (5' end of NADH
      dehydrogenase subunit 7) that have open, accessible anchor binding sites show
      very efficient gRNA targeting. Electrophoretic mobility shift assays indicate
      that the cognate gRNA for ND7-550 had 10-fold higher affinity for its mRNA than
      the A6 pair. Surface plasmon resonance studies indicate that the difference in
      affinity was due to a four-fold faster association rate. As expected, mRNAs with
      considerable structure surrounding the anchor binding sites were less accessible
      and had very low affinity for their cognate gRNAs. In vitro editing assays
      indicate that efficient pairing is crucial for gRNA directed cleavage. However,
      only the A6 substrate showed gRNA-directed cleavage at the correct editing site.
      This suggests that different gRNA/mRNA pairs may require different "sets" of
      accessory factors for efficient editing. By characterizing a number of different
      gRNA/mRNA interactions, we may be able to define a "bank" of RNA editing
      substrates with different putative chaperone and other co-factor requirements.
      This will allow the more efficient identification and characterization of
      transcript specific RNA editing accessory proteins.

PMID- 20808933
TI  - Extreme evolutionary disparities seen in positive selection across seven complex
      diseases.
AB  - Positive selection is known to occur when the environment that an organism
      inhabits is suddenly altered, as is the case across recent human history. Genome
      wide association studies (GWASs) have successfully illuminated disease-associated
      variation. However, whether human evolution is heading towards or away from
      disease susceptibility in general remains an open question. The genetic-basis of
      common complex disease may partially be caused by positive selection events,
      which simultaneously increased fitness and susceptibility to disease. We analyze
      seven diseases studied by the Wellcome Trust Case Control Consortium to compare
      evidence for selection at every locus associated with disease. We take a large
      set of the most strongly associated SNPs in each GWA study in order to capture
      more hidden associations at the cost of introducing false positives into our
      analysis. We then search for signs of positive selection in this inclusive set of
      SNPs. There are striking differences between the seven studied diseases. We find
      alleles increasing susceptibility to Type 1 Diabetes (T1D), Rheumatoid Arthritis
      (RA), and Crohn's Disease (CD) underwent recent positive selection. There is more
      selection in alleles increasing, rather than decreasing, susceptibility to T1D.
      In the 80 SNPs most associated with T1D (p-value <7.01 x 10(-5)) showing strong
      signs of positive selection, 58 alleles associated with disease susceptibility
      show signs of positive selection, while only 22 associated with disease
      protection show signs of positive selection. Alleles increasing susceptibility to
      RA are under selection as well. In contrast, selection in SNPs associated with CD
      favors protective alleles. These results inform the current understanding of
      disease etiology, shed light on potential benefits associated with the genetic
      basis of disease, and aid in the efforts to identify causal genetic factors
      underlying complex disease.

PMID- 20808934
TI  - Overexpression of inosine 5'-monophosphate dehydrogenase type II mediates
      chemoresistance to human osteosarcoma cells.
AB  - BACKGROUND: Chemoresistance is the principal reason for poor survival and disease
      recurrence in osteosarcoma patients. Inosine 5'-monophosphate dehydrogenase type
      II (IMPDH2) encodes the rate-limiting enzyme in the de novo guanine nucleotide
      biosynthesis and has been linked to cell growth, differentiation, and malignant
      transformation. In a previous study we identified IMPDH2 as an independent
      prognostic factor and observed frequent IMPDH2 overexpression in osteosarcoma
      patients with poor response to chemotherapy. The aim of this study was to provide
      evidence for direct involvement of IMPDH2 in the development of chemoresistance.
      METHODOLOGY/PRINCIPAL FINDINGS: Stable cell lines overexpressing IMPDH2 and
      IMPDH2 knock-down cells were generated using the osteosarcoma cell line Saos-2 as
      parental cell line. Chemosensitivity, proliferation, and the expression of
      apoptosis-related proteins were analyzed by flow cytometry, WST-1-assay, and
      western blot analysis. Overexpression of IMPDH2 in Saos-2 cells induced strong
      chemoresistance against cisplatin and methotrexate. The observed chemoresistance
      was mediated at least in part by increased expression of the anti-apoptotic
      proteins Bcl-2, Mcl-1, and XIAP, reduced activation of caspase-9, and,
      consequently, reduced cleavage of the caspase substrate PARP. Pharmacological
      inhibition of IMPDH induced a moderate reduction of cell viability and a strong
      decrease of cell proliferation, but no increase in chemosensitivity. However,
      chemoresistant IMPDH2-overexpressing cells could be resensitized by RNA
      interference-mediated downregulation of IMPDH2. CONCLUSIONS: IMPDH2 is directly
      involved in the development of chemoresistance in osteosarcoma cells, suggesting
      that targeting of IMPDH2 by RNAi or more effective pharmacological inhibitors in
      combination with chemotherapy might be a promising means of overcoming
      chemoresistance in osteosarcomas with high IMPDH2 expression.

PMID- 20808935
TI  - Mesenchymal stem cells promote mammosphere formation and decrease E-cadherin in
      normal and malignant breast cells.
AB  - INTRODUCTION: Normal and malignant breast tissue contains a rare population of
      multi-potent cells with the capacity to self-renew, referred to as stem cells, or
      tumor initiating cells (TIC). These cells can be enriched by growth as
      "mammospheres" in three-dimensional cultures. OBJECTIVE: We tested the hypothesis
      that human bone-marrow derived mesenchymal stem cells (MSC), which are known to
      support tumor growth and metastasis, increase mammosphere formation. RESULTS: We
      found that MSC increased human mammary epithelial cell (HMEC) mammosphere
      formation in a dose-dependent manner. A similar increase in sphere formation was
      seen in human inflammatory (SUM149) and non-inflammatory breast cancer cell lines
      (MCF-7) but not in primary inflammatory breast cancer cells (MDA-IBC-3). We
      determined that increased mammosphere formation can be mediated by secreted
      factors as MSC conditioned media from MSC spheroids significantly increased HMEC,
      MCF-7 and SUM149 mammosphere formation by 6.4 to 21-fold. Mammospheres grown in
      MSC conditioned media had lower levels of the cell adhesion protein, E-cadherin,
      and increased expression of N-cadherin in SUM149 and HMEC cells, characteristic
      of a pro-invasive mesenchymal phenotype. Co-injection with MSC in vivo resulted
      in a reduced latency time to develop detectable MCF-7 and MDA-IBC-3 tumors and
      increased the growth of MDA-IBC-3 tumors. Furthermore, E-cadherin expression was
      decreased in MDA-IBC-3 xenografts with co-injection of MSC. CONCLUSIONS: MSC
      increase the efficiency of primary mammosphere formation in normal and malignant
      breast cells and decrease E-cadherin expression, a biologic event associated with
      breast cancer progression and resistance to therapy.

PMID- 20808936
TI  - Hepatic gene expression profiling reveals key pathways involved in leptin
      mediated weight loss in ob/ob mice.
AB  - BACKGROUND: Leptin, a cytokine-like protein, plays an important role in the
      regulation of body weight through inhibition of food intake and stimulation of
      energy expenditure. Leptin circulates in blood and acts on the brain, which sends
      downstream signals to regulate body weight. Leptin therapy has been successful in
      treating leptin deficient obese patients. However, high levels of leptin have
      been observed in more common forms of obesity indicating a state of leptin
      resistance which limits the application of leptin in the treatment of obesity. If
      the central effect of leptin could be by-passed and genes which respond to leptin
      treatment could be regulated directly, new therapeutic targets for the treatment
      of obesity may be possible. The purpose of this study was to identify genes and
      subsequent pathways correlated with leptin-mediated weight loss.
      METHODOLOGY/PRINCIPAL FINDINGS: WE UTILIZED MICROARRAY TECHNOLOGY TO COMPARE
      HEPATIC GENE EXPRESSION CHANGES AFTER TWO TYPES OF LEPTIN ADMINISTRATION: one
      involving a direct stimulatory effect when administered peripherally
      (subcutaneous: SQ) and another that is indirect, involving a hypothalamic relay
      that suppresses food intake when leptin is administered centrally
      (intracerebroventricular: ICV). We identified 214 genes that correlate with
      leptin mediated weight loss. Several biological processes such as mitochondrial
      metabolic pathways, lipid metabolic and catabolic processes, lipid biosynthetic
      processes, carboxylic acid metabolic processes, iron ion binding and glutathione
      S-transferases were downregulated after leptin administration. In contrast, genes
      involved in the immune system inflammatory response and lysosomal activity were
      found to be upregulated. Among the cellular compartments mitochondrion (32
      genes), endoplasmic reticulum (22 genes) and vacuole (8 genes) were significantly
      over represented. CONCLUSIONS/SIGNIFICANCE: In this study we have identified key
      molecular pathways and downstream genes which respond to leptin treatment and are
      involved in leptin-mediated weight loss. Many of these genes have previously been
      shown to be associated with obesity; however, we have also identified a number of
      other novel target genes. Further investigation will be required to assess the
      possible use of these genes and their associated protein products as therapeutic
      targets for the treatment of obesity.

PMID- 20808937
TI  - Relationships between levels of serum IgE, cell-bound IgE, and IgE-receptors on
      peripheral blood cells in a pediatric population.
AB  - BACKGROUND: Elevated serum immunoglobulin (Ig) E is a diagnostic marker of
      immediate-type allergic reactions. We hypothesize that serum IgE does not
      necessarily reflect total body IgE because in vivo IgE can be bound to cell
      surface receptors such as FcepsilonRI and FcepsilonRII (CD23). The aim of this
      study was to analyze the relationships between levels of serum IgE, cell-bound
      IgE, and IgE-receptors on peripheral blood cells in a pediatric population.
      METHODOLOGY: Whole blood samples from 48 children (26 boys, 22 girls, mean age
      10,3+/-5,4 years) were analyzed by flow cytometry for FcepsilonRI, CD23, and cell
      bound IgE on dendritic cells (CD11c+MHC class II+), monocytes (CD14+), basophils
      (CD123+MHC class II-) and neutrophils (myeloperoxidase+). Total serum IgE was
      measured by ELISA and converted into z-units to account for age-dependent normal
      ranges. Correlations were calculated using Spearman rank correlation test.
      PRINCIPAL FINDINGS: Dendritic cells, monocytes, basophils, and neutrophils
      expressed the high affinity IgE-receptor FcepsilonRI. Dendritic cells and
      monocytes also expressed the low affinity receptor CD23. The majority of IgE
      receptor positive cells carried IgE on their surface. Expression of both IgE
      receptors was tightly correlated with cell-bound IgE. In general, cell-bound IgE
      on FcepsilonRI+ cells correlated well with serum IgE. However, some patients
      carried high amounts of cell-bound IgE despite low total serum IgE levels.
      CONCLUSION/SIGNIFICANCE: In pediatric patients, levels of age-adjusted serum IgE,
      cell-bound IgE, and FcepsilonRI correlate. Even in the absence of elevated levels
      of serum IgE, cell-bound IgE can be detected on peripheral blood cells in a
      subgroup of patients.

PMID- 20808938
TI  - Enzyme replacement in a human model of mucopolysaccharidosis IVA in vitro and its
      biodistribution in the cartilage of wild type mice.
AB  - Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage
      disorder caused by deficiency of N-acetylgalactosamine-6-sulfatase (GALNS), an
      enzyme that degrades keratan sulfate (KS). Currently no therapy for MPS IVA is
      available. We produced recombinant human (rh)GALNS as a potential enzyme
      replacement therapy for MPS IVA. Chinese hamster ovary cells stably
      overexpressing GALNS and sulfatase modifying factor-1 were used to produce active
      ( approximately 2 U/mg) and pure (>or=97%) rhGALNS. The recombinant enzyme was
      phosphorylated and was dose-dependently taken up by mannose-6-phosphate receptor
      (K(uptake) = 2.5 nM), thereby restoring enzyme activity in MPS IVA fibroblasts.
      In the absence of an animal model with a skeletal phenotype, we established
      chondrocytes isolated from two MPS IVA patients as a disease model in vitro. MPS
      IVA chondrocyte GALNS activity was not detectable and the cells exhibited KS
      storage up to 11-fold higher than unaffected chondrocytes. MPS IVA chondrocytes
      internalized rhGALNS into lysosomes, resulting in normalization of enzyme
      activity and decrease in KS storage. rhGALNS treatment also modulated gene
      expression, increasing expression of chondrogenic genes Collagen II, Collagen X,
      Aggrecan and Sox9 and decreasing abnormal expression of Collagen I. Intravenous
      administration of rhGALNS resulted in biodistribution throughout all layers of
      the heart valve and the entire thickness of the growth plate in wild-type mice.
      We show that enzyme replacement therapy with recombinant human GALNS results in
      clearance of keratan sulfate accumulation, and that such treatment ameliorates
      aberrant gene expression in human chondrocytes in vitro. Penetration of the
      therapeutic enzyme throughout poorly vascularized, but clinically relevant
      tissues, including growth plate cartilage and heart valve, as well as macrophages
      and hepatocytes in wild-type mouse, further supports development of rhGALNS as
      enzyme replacement therapy for MPS IVA.

PMID- 20808939
TI  - A pandemic influenza H1N1 live vaccine based on modified vaccinia Ankara is
      highly immunogenic and protects mice in active and passive immunizations.
AB  - BACKGROUND: The development of novel influenza vaccines inducing a broad immune
      response is an important objective. The aim of this study was to evaluate live
      vaccines which induce both strong humoral and cell-mediated immune responses
      against the novel human pandemic H1N1 influenza virus, and to show protection in
      a lethal animal challenge model. METHODOLOGY/PRINCIPAL FINDINGS: For this
      purpose, the hemagglutinin (HA) and neuraminidase (NA) genes of the influenza
      A/California/07/2009 (H1N1) strain (CA/07) were inserted into the replication
      deficient modified vaccinia Ankara (MVA) virus--a safe poxviral live vector-
      resulting in MVA-H1-Ca and MVA-N1-Ca vectors. These live vaccines, together with
      an inactivated whole virus vaccine, were assessed in a lung infection model using
      immune competent Balb/c mice, and in a lethal challenge model using severe
      combined immunodeficient (SCID) mice after passive serum transfer from immunized
      mice. Balb/c mice vaccinated with the MVA-H1-Ca virus or the inactivated vaccine
      were fully protected from lung infection after challenge with the influenza H1N1
      wild-type strain, while the neuraminidase virus MVA-N1-Ca induced only partial
      protection. The live vaccines were already protective after a single dose and
      induced substantial amounts of neutralizing antibodies and of interferon-gamma
      secreting (IFN-gamma) CD4- and CD8 T-cells in lungs and spleens. In the lungs, a
      rapid increase of HA-specific CD4- and CD8 T cells was observed in vaccinated
      mice shortly after challenge with influenza swine flu virus, which probably
      contributes to the strong inhibition of pulmonary viral replication observed. In
      addition, passive transfer of antisera raised in MVA-H1-Ca vaccinated immune
      competent mice protected SCID mice from lethal challenge with the CA/07 wild-type
      virus. CONCLUSIONS/SIGNIFICANCE: The non-replicating MVA-based H1N1 live vaccines
      induce a broad protective immune response and are promising vaccine candidates
      for pandemic influenza.

PMID- 20808940
TI  - Shear stress modulation of smooth muscle cell marker genes in 2-D and 3-D depends
      on mechanotransduction by heparan sulfate proteoglycans and ERK1/2.
AB  - BACKGROUND: During vascular injury, vascular smooth muscle cells (SMCs) and
      fibroblasts/myofibroblasts (FBs/MFBs) are exposed to altered luminal blood flow
      or transmural interstitial flow. We investigate the effects of these two types of
      fluid flows on the phenotypes of SMCs and MFBs and the underlying
      mechanotransduction mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: Exposure to 8
      dyn/cm(2) laminar flow shear stress (2-dimensional, 2-D) for 15 h significantly
      reduced expression of alpha-smooth muscle actin (alpha-SMA), smooth muscle
      protein 22 (SM22), SM myosin heavy chain (SM-MHC), smoothelin, and calponin.
      Cells suspended in collagen gels were exposed to interstitial flow (1 cmH(2)O,
      approximately 0.05 dyn/cm(2), 3-D), and after 6 h of exposure, expression of SM
      MHC, smoothelin, and calponin were significantly reduced, while expression of
      alpha-SMA and SM22 were markedly enhanced. PD98059 (an ERK1/2 inhibitor) and
      heparinase III (an enzyme to cleave heparan sulfate) significantly blocked the
      effects of laminar flow on gene expression, and also reversed the effects of
      interstitial flow on SM-MHC, smoothelin, and calponin, but enhanced interstitial
      flow-induced expression of alpha-SMA and SM22. SMCs and MFBs have similar
      responses to fluid flow. Silencing ERK1/2 completely blocked the effects of both
      laminar flow and interstitial flow on SMC marker gene expression. Western
      blotting showed that both types of flows induced ERK1/2 activation that was
      inhibited by disruption of heparan sulfate proteoglycans (HSPGs).
      CONCLUSIONS/SIGNIFICANCE: The results suggest that HSPG-mediated ERK1/2
      activation is an important mechanotransduction pathway modulating SMC marker gene
      expression when SMCs and MFBs are exposed to flow. Fluid flow may be involved in
      vascular remodeling and lesion formation by affecting phenotypes of vascular wall
      cells. This study has implications in understanding the flow-related
      mechanobiology in vascular lesion formation, tumor cell invasion, and stem cell
      differentiation.

PMID- 20808941
TI  - DNA methylation profiles and their relationship with cytogenetic status in adult
      acute myeloid leukemia.
AB  - BACKGROUND: Aberrant promoter DNA methylation has been shown to play a role in
      acute myeloid leukemia (AML) pathophysiology. However, further studies to discuss
      the prognostic value and the relationship of the epigenetic signatures with
      defined genomic rearrangements in acute myeloid leukemia are required.
      METHODOLOGY/PRINCIPAL FINDINGS: We carried out high-throughput methylation
      profiling on 116 de novo AML cases and we validated the significant biomarkers in
      an independent cohort of 244 AML cases. Methylation signatures were associated
      with the presence of a specific cytogenetic status. In normal karyotype cases,
      aberrant methylation of the promoter of DBC1 was validated as a predictor of the
      disease-free and overall survival. Furthermore, DBC1 expression was significantly
      silenced in the aberrantly methylated samples. Patients with chromosome
      rearrangements showed distinct methylation signatures. To establish the role of
      fusion proteins in the epigenetic profiles, 20 additional samples of human
      hematopoietic stem/progenitor cells (HSPC) transduced with common fusion genes
      were studied and compared with patient samples carrying the same rearrangements.
      The presence of MLL rearrangements in HSPC induced the methylation profile
      observed in the MLL-positive primary samples. In contrast, fusion genes such as
      AML1/ETO or CBFB/MYH11 failed to reproduce the epigenetic signature observed in
      the patients. CONCLUSIONS/SIGNIFICANCE: Our study provides a comprehensive
      epigenetic profiling of AML, identifies new clinical markers for cases with a
      normal karyotype, and reveals relevant biological information related to the role
      of fusion proteins on the methylation signature.

PMID- 20808942
TI  - Increased genetic diversity of HIV-1 circulating in Hong Kong.
AB  - HIV-1 group M strains are characterized into 9 pure subtypes and 48 circulating
      recombinant forms (CRFs). Recent studies have identified the presence of new HIV
      1 recombinants in Hong Kong and their complexity continues to increase. This
      study aims to characterize the HIV-1 genetic diversity in Hong Kong. Phylogenetic
      analyses were performed by using HIV-1 pol sequences including protease and
      partial reverse transcriptase isolated from 1045 local patients in Hong Kong from
      2003 to 2008. For the pol sequences with unassigned genotype, the evidence of
      recombination was determined by using sliding-window based bootscan plots and
      their env C2V3 region were also sequenced. Epidemiological background of these
      patients was further collected. The pol phylogenetic analyses highlighted the
      extent of HIV-1 genetic diversity in Hong Kong. Subtype B (450/1045; 43.1%) and
      CRF01_AE (469/1045; 44.9%) variants were clearly predominant. Other genotypes
      (126/1045; 12.1%) including 3 defined subtypes, 10 CRFs, 1 unassigned subtype and
      33 recombinants with 11 different mosaic patterns were observed. Recombinants of
      subtype B and CRF01_AE were mainly found among local Chinese MSM throughout 2004
      to 2008, while the CRF02_AG and subtype G recombinants were circulating among non
      Chinese Asian population in Hong Kong through heterosexual transmission starting
      from 2008. Our study demonstrated the complex recombination of HIV-1 in Hong Kong
      and the need in developing surveillance system for tracking the distribution of
      new HIV-1 genetic variants.

PMID- 20808943
TI  - A new measure of centrality for brain networks.
AB  - Recent developments in network theory have allowed for the study of the structure
      and function of the human brain in terms of a network of interconnected
      components. Among the many nodes that form a network, some play a crucial role
      and are said to be central within the network structure. Central nodes may be
      identified via centrality metrics, with degree, betweenness, and eigenvector
      centrality being three of the most popular measures. Degree identifies the most
      connected nodes, whereas betweenness centrality identifies those located on the
      most traveled paths. Eigenvector centrality considers nodes connected to other
      high degree nodes as highly central. In the work presented here, we propose a new
      centrality metric called leverage centrality that considers the extent of
      connectivity of a node relative to the connectivity of its neighbors. The
      leverage centrality of a node in a network is determined by the extent to which
      its immediate neighbors rely on that node for information. Although similar in
      concept, there are essential differences between eigenvector and leverage
      centrality that are discussed in this manuscript. Degree, betweenness,
      eigenvector, and leverage centrality were compared using functional brain
      networks generated from healthy volunteers. Functional cartography was also used
      to identify neighborhood hubs (nodes with high degree within a network
      neighborhood). Provincial hubs provide structure within the local community, and
      connector hubs mediate connections between multiple communities. Leverage proved
      to yield information that was not captured by degree, betweenness, or eigenvector
      centrality and was more accurate at identifying neighborhood hubs. We propose
      that this metric may be able to identify critical nodes that are highly
      influential within the network.

PMID- 20808945
TI  - The PPCD1 mouse: characterization of a mouse model for posterior polymorphous
      corneal dystrophy and identification of a candidate gene.
AB  - The PPCD1 mouse, a spontaneous mutant that arose in our mouse colony, is
      characterized by an enlarged anterior chamber resulting from metaplasia of the
      corneal endothelium and blockage of the iridocorneal angle by epithelialized
      corneal endothelial cells. The presence of stratified multilayered corneal
      endothelial cells with abnormal patterns of cytokeratin expression are remarkably
      similar to those observed in human posterior polymorphous corneal dystrophy
      (PPCD) and the sporadic condition, iridocorneal endothelial syndrome. Affected
      eyes exhibit epithelialized corneal endothelial cells, with inappropriate
      cytokeratin expression and proliferation over the iridocorneal angle and
      posterior cornea. We have termed this the "mouse PPCD1" phenotype and mapped the
      mouse locus for this phenotype, designated "Ppcd1", to a 6.1 Mbp interval on
      Chromosome 2, which is syntenic to the human Chromosome 20 PPCD1 interval.
      Inheritance of the mouse PPCD1 phenotype is autosomal dominant, with complete
      penetrance on the sensitive DBA/2J background and decreased penetrance on the
      C57BL/6J background. Comparative genome hybridization has identified a hemizygous
      78 Kbp duplication in the mapped interval. The endpoints of the duplication are
      located in positions that disrupt the genes Csrp2bp and 6330439K17Rik and lead to
      duplication of the pseudogene LOC100043552. Quantitative reverse transcriptase
      PCR indicates that expression levels of Csrp2bp and 6330439K17Rik are decreased
      in eyes of PPCD1 mice. Based on the observations of decreased gene expression
      levels, association with ZEB1-related pathways, and the report of corneal
      opacities in Csrp2bp(tm1a(KOMP)Wtsi) heterozygotes and embryonic lethality in
      nulls, we postulate that duplication of the 78 Kbp segment leading to
      haploinsufficiency of Csrp2bp is responsible for the mouse PPCD1 phenotype.
      Similarly, CSRP2BP haploinsufficiency may lead to human PPCD.

PMID- 20808944
TI  - Prenatal exposure to maternal depressed mood and the MTHFR C677T variant affect
      SLC6A4 methylation in infants at birth.
AB  - BACKGROUND: Prenatal and early postnatal exposure to maternal depression may
      "program" childhood behavior via epigenetic processes such as DNA methylation.
      Methylenetetrahydro-folate reductase (MTHFR) is an important enzyme in the
      generation of methyl groups for DNA methylation. The common MTHFR C677T variant
      is associated with depression in men and non-pregnant women, and with global
      changes in DNA methylation. This study investigated the effect of maternal MTHFR
      C677T genotype on antenatal maternal mood, and their impact on the gene-specific
      methylation in pregnant women and their newborn infants. The methylation status
      of SLC6A4, which encodes the transmembrane serotonin transporter, and BDNF, which
      encodes brain derived neurotrophic factor, were assessed because of their
      potential role in behaviour. METHODS/PRINCIPAL FINDINGS: Depressed mood was
      assessed by the Edinburgh Postnatal Depression Scale (EPDS) and the Hamilton
      Rating Scale for Depression (HAM-D) in women (n = 82, all taking folate) during
      the 2(nd) and 3(rd) trimesters of pregnancy. The methylation status of SLC6A4 and
      BDNF were assessed in 3rd trimester maternal peripheral leukocytes and in
      umbilical cord leukocytes collected from their infants at birth. Women with the
      MTHFR 677TT genotype had greater 2(nd) trimester depressed mood (p<0.05).
      Increased 2(nd) trimester maternal depressed mood (EPDS scores) was associated
      with decreased maternal and infant SLC6A4 promoter methylation (p<0.05), but had
      no effect on BDNF promoter methylation. CONCLUSIONS: These findings show that the
      MTHFR C677T variant is associated with greater depressed mood during pregnancy.
      We further showed that prenatal exposure to maternal depressed mood affects gene
      specific DNA methylation patterns. These findings support the concept that
      alterations in epigenetic processes may contribute to developmental programming
      of behaviour by maternal depression.

PMID- 20808946
TI  - Differential effects of concomitant use of vitamins C and E on trophoblast
      apoptosis and autophagy between normoxia and hypoxia-reoxygenation.
AB  - BACKGROUND: Concomitant supplementation of vitamins C and E during pregnancy has
      been reportedly associated with low birth weight, the premature rupture of
      membranes and fetal loss or perinatal death in women at risk for preeclampsia;
      however, the cause is unknown. We surmise that hypoxia-reoxygenation (HR) within
      the intervillous space due to abnormal placentation is the mechanism and
      hypothesize that concomitant administration of aforementioned vitamin
      antioxidants detrimentally affects trophoblast cells during HR.
      METHODOLOGY/PRINCIPAL FINDINGS: Using villous explants, concomitant
      administration of 50 microM of vitamins C and E was observed to reduce apoptotic
      and autophagic changes in the trophoblast layer at normoxia (8% oxygen) but to
      cause more prominent apoptosis and autophagy during HR. Furthermore, increased
      levels of Bcl-2 and Bcl-xL in association with a decrease in the autophagy
      related protein LC3-II were noted in cytotrophoblastic cells treated with
      vitamins C and E under standard culture conditions. In contrast, vitamin
      treatment decreased Bcl-2 and Bcl-xL as well as increased mitochondrial Bak and
      cytosolic LC3-II in cytotrophoblasts subjected to HR. CONCLUSIONS/SIGNIFICANCE:
      Our results indicate that concomitant administration of vitamins C and E has
      differential effects on the changes of apoptosis, autophagy and the expression of
      Bcl-2 family of proteins in the trophoblasts between normoxia and HR. These
      changes may probably lead to the impairment of placental function and suboptimal
      growth of the fetus.

PMID- 20808947
TI  - High-fat diet: bacteria interactions promote intestinal inflammation which
      precedes and correlates with obesity and insulin resistance in mouse.
AB  - BACKGROUND: Obesity induced by high fat (HF) diet is associated with inflammation
      which contributes to development of insulin resistance. Most prior studies have
      focused on adipose tissue as the source of obesity-associated inflammation.
      Increasing evidence links intestinal bacteria to development of diet-induced
      obesity (DIO). This study tested the hypothesis that HF western diet and gut
      bacteria interact to promote intestinal inflammation, which contributes to the
      progression of obesity and insulin resistance. METHODOLOGY/PRINCIPAL FINDINGS:
      Conventionally raised specific-pathogen free (CONV) and germ-free (GF) mice were
      given HF or low fat (LF) diet for 2-16 weeks. Body weight and adiposity were
      measured. Intestinal inflammation was assessed by evaluation of TNF-alpha mRNA
      and activation of a NF-kappaB(EGFP) reporter gene. In CONV but not GF mice, HF
      diet induced increases in body weight and adiposity. HF diet induced ileal TNF
      alpha mRNA in CONV but not GF mice and this increase preceded obesity and
      strongly and significantly correlated with diet induced weight gain, adiposity,
      plasma insulin and glucose. In CONV mice HF diet also resulted in activation of
      NF-kappaB(EGFP) in epithelial cells, immune cells and endothelial cells of small
      intestine. Further experiments demonstrated that fecal slurries from CONV mice
      fed HF diet are sufficient to activate NF-kappaB(EGFP) in GF NF-kappaB(EGFP)
      mice. CONCLUSIONS/SIGNIFICANCE: Bacteria and HF diet interact to promote
      proinflammatory changes in the small intestine, which precede weight gain and
      obesity and show strong and significant associations with progression of obesity
      and development of insulin resistance. To our knowledge, this is the first
      evidence that intestinal inflammation is an early consequence of HF diet which
      may contribute to obesity and associated insulin resistance. Interventions which
      limit intestinal inflammation induced by HF diet and bacteria may protect against
      obesity and insulin resistance.

PMID- 20808948
TI  - Binding of protein kinase inhibitors to synapsin I inferred from pair-wise
      binding site similarity measurements.
AB  - Predicting off-targets by computational methods is getting increasing importance
      in early drug discovery stages. We herewith present a computational method based
      on binding site three-dimensional comparisons, which prompted us to investigate
      the cross-reaction of protein kinase inhibitors with synapsin I, an ATP-binding
      protein regulating neurotransmitter release in the synapse. Systematic pair-wise
      comparison of the staurosporine-binding site of the proto-oncogene Pim-1 kinase
      with 6,412 druggable protein-ligand binding sites suggested that the ATP-binding
      site of synapsin I may recognize the pan-kinase inhibitor staurosporine.
      Biochemical validation of this hypothesis was realized by competition experiments
      of staurosporine with ATP-gamma(35)S for binding to synapsin I. Staurosporine, as
      well as three other inhibitors of protein kinases (cdk2, Pim-1 and casein kinase
      type 2), effectively bound to synapsin I with nanomolar affinities and promoted
      synapsin-induced F-actin bundling. The selective Pim-1 kinase inhibitor
      quercetagetin was shown to be the most potent synapsin I binder (IC50 = 0.15
      microM), in agreement with the predicted binding site similarities between
      synapsin I and various protein kinases. Other protein kinase inhibitors (protein
      kinase A and chk1 inhibitor), kinase inhibitors (diacylglycerolkinase inhibitor)
      and various other ATP-competitors (DNA topoisomerase II and HSP-90alpha
      inhibitors) did not bind to synapsin I, as predicted from a lower similarity of
      their respective ATP-binding sites to that of synapsin I. The present data
      suggest that the observed downregulation of neurotransmitter release by some but
      not all protein kinase inhibitors may also be contributed by a direct binding to
      synapsin I and phosphorylation-independent perturbation of synapsin I function.
      More generally, the data also demonstrate that cross-reactivity with various
      targets may be detected by systematic pair-wise similarity measurement of ligand
      annotated binding sites.

PMID- 20808949
TI  - The United States of America and scientific research.
AB  - To gauge the current commitment to scientific research in the United States of
      America (US), we compared federal research funding (FRF) with the US gross
      domestic product (GDP) and industry research spending during the past six
      decades. In order to address the recent globalization of scientific research, we
      also focused on four key indicators of research activities: research and
      development (R&D) funding, total science and engineering doctoral degrees,
      patents, and scientific publications. We compared these indicators across three
      major population and economic regions: the US, the European Union (EU) and the
      People's Republic of China (China) over the past decade. We discovered a number
      of interesting trends with direct relevance for science policy. The level of US
      FRF has varied between 0.2% and 0.6% of the GDP during the last six decades.
      Since the 1960s, the US FRF contribution has fallen from twice that of industrial
      research funding to roughly equal. Also, in the last two decades, the portion of
      the US government R&D spending devoted to research has increased. Although well
      below the US and the EU in overall funding, the current growth rate for R&D
      funding in China greatly exceeds that of both. Finally, the EU currently produces
      more science and engineering doctoral graduates and scientific publications than
      the US in absolute terms, but not per capita. This study's aim is to facilitate a
      serious discussion of key questions by the research community and federal policy
      makers. In particular, our results raise two questions with respect to: a) the
      increasing globalization of science: "What role is the US playing now, and what
      role will it play in the future of international science?"; and b) the ability to
      produce beneficial innovations for society: "How will the US continue to foster
      its strengths?"

PMID- 20808950
TI  - Hyperpolarized Xe MR imaging of alveolar gas uptake in humans.
AB  - BACKGROUND: One of the central physiological functions of the lungs is to
      transfer inhaled gases from the alveoli to pulmonary capillary blood. However,
      current measures of alveolar gas uptake provide only global information and thus
      lack the sensitivity and specificity needed to account for regional variations in
      gas exchange. METHODS AND PRINCIPAL FINDINGS: Here we exploit the solubility,
      high magnetic resonance (MR) signal intensity, and large chemical shift of
      hyperpolarized (HP) (129)Xe to probe the regional uptake of alveolar gases by
      directly imaging HP (129)Xe dissolved in the gas exchange tissues and pulmonary
      capillary blood of human subjects. The resulting single breath-hold, three
      dimensional MR images are optimized using millisecond repetition times and high
      flip angle radio-frequency pulses, because the dissolved HP (129)Xe magnetization
      is rapidly replenished by diffusive exchange with alveolar (129)Xe. The dissolved
      HP (129)Xe MR images display significant, directional heterogeneity, with
      increased signal intensity observed from the gravity-dependent portions of the
      lungs. CONCLUSIONS: The features observed in dissolved-phase (129)Xe MR images
      are consistent with gravity-dependent lung deformation, which produces increased
      ventilation, reduced alveolar size (i.e., higher surface-to-volume ratios),
      higher tissue densities, and increased perfusion in the dependent portions of the
      lungs. Thus, these results suggest that dissolved HP (129)Xe imaging reports on
      pulmonary function at a fundamental level.

PMID- 20808951
TI  - Quantitative analysis of the Drosophila segmentation regulatory network using
      pattern generating potentials.
AB  - Cis-regulatory modules that drive precise spatial-temporal patterns of gene
      expression are central to the process of metazoan development. We describe a new
      computational strategy to annotate genomic sequences based on their "pattern
      generating potential" and to produce quantitative descriptions of transcriptional
      regulatory networks at the level of individual protein-module interactions. We
      use this approach to convert the qualitative understanding of interactions that
      regulate Drosophila segmentation into a network model in which a confidence value
      is associated with each transcription factor-module interaction. Sequence
      information from multiple Drosophila species is integrated with transcription
      factor binding specificities to determine conserved binding site frequencies
      across the genome. These binding site profiles are combined with transcription
      factor expression information to create a model to predict module activity
      patterns. This model is used to scan genomic sequences for the potential to
      generate all or part of the expression pattern of a nearby gene, obtained from
      available gene expression databases. Interactions between individual
      transcription factors and modules are inferred by a statistical method to
      quantify a factor's contribution to the module's pattern generating potential. We
      use these pattern generating potentials to systematically describe the location
      and function of known and novel cis-regulatory modules in the segmentation
      network, identifying many examples of modules predicted to have overlapping
      expression activities. Surprisingly, conserved transcription factor binding site
      frequencies were as effective as experimental measurements of occupancy in
      predicting module expression patterns or factor-module interactions. Thus, unlike
      previous module prediction methods, this method predicts not only the location of
      modules but also their spatial activity pattern and the factors that directly
      determine this pattern. As databases of transcription factor specificities and in
      vivo gene expression patterns grow, analysis of pattern generating potentials
      provides a general method to decode transcriptional regulatory sequences and
      networks.

PMID- 20808953
TI  - Aging in a long-lived clonal tree.
AB  - From bacteria to multicellular animals, most organisms exhibit declines in
      survivorship or reproductive performance with increasing age ("senescence").
      Evidence for senescence in clonal plants, however, is scant. During asexual
      growth, we expect that somatic mutations, which negatively impact sexual fitness,
      should accumulate and contribute to senescence, especially among long-lived
      clonal plants. We tested whether older clones of Populus tremuloides (trembling
      aspen) from natural stands in British Columbia exhibited significantly reduced
      reproductive performance. Coupling molecular-based estimates of clone age with
      male fertility data, we observed a significant decline in the average number of
      viable pollen grains per catkin per ramet with increasing clone age in trembling
      aspen. We found that mutations reduced relative male fertility in clonal aspen
      populations by about 5.8 x 10(-5) to 1.6 x 10(-3) per year, leading to an 8%
      reduction in the number of viable pollen grains, on average, among the clones
      studied. The probability that an aspen lineage ultimately goes extinct rises as
      its male sexual fitness declines, suggesting that even long-lived clonal
      organisms are vulnerable to senescence.

PMID- 20808952
TI  - MLL2 is required in oocytes for bulk histone 3 lysine 4 trimethylation and
      transcriptional silencing.
AB  - During gametogenesis and pre-implantation development, the mammalian epigenome is
      reprogrammed to establish pluripotency in the epiblast. Here we show that the
      histone 3 lysine 4 (H3K4) methyltransferase, MLL2, controls most of the promoter
      specific chromatin modification, H3K4me3, during oogenesis and early development.
      Using conditional knockout mutagenesis and a hypomorph model, we show that Mll2
      deficiency in oocytes results in anovulation and oocyte death, with increased
      transcription of p53, apoptotic factors, and Iap elements. MLL2 is required for
      (1) bulk H3K4me3 but not H3K4me1, indicating that MLL2 controls most promoters
      but monomethylation is regulated by a different H3K4 methyltransferase; (2) the
      global transcriptional silencing that preceeds resumption of meiosis but not for
      the concomitant nuclear reorganization into the surrounded nucleolus (SN)
      chromatin configuration; (3) oocyte survival; and (4) normal zygotic genome
      activation. These results reveal that MLL2 is autonomously required in oocytes
      for fertility and imply that MLL2 contributes to the epigenetic reprogramming
      that takes place before fertilization. We propose that once this task has been
      accomplished, MLL2 is not required until gastrulation and that other
      methyltransferases are responsible for bulk H3K4me3, thereby revealing an
      unexpected epigenetic control switch amongst the H3K4 methyltransferases during
      development.

PMID- 20808954
TI  - We all gotta go sometime.

PMID- 20808955
TI  - The costs and underappreciated consequences of research misconduct: a case study.

PMID- 20808956
TI  - Moving from data on deaths to public health policy in Agincourt, South Africa:
      approaches to analysing and understanding verbal autopsy findings.
AB  - BACKGROUND: Cause of death data are an essential source for public health
      planning, but their availability and quality are lacking in many parts of the
      world. Interviewing family and friends after a death has occurred (a procedure
      known as verbal autopsy) provides a source of data where deaths otherwise go
      unregistered; but sound methods for interpreting and analysing the ensuing data
      are essential. Two main approaches are commonly used: either physicians review
      individual interview material to arrive at probable cause of death, or
      probabilistic models process the data into likely cause(s). Here we compare and
      contrast these approaches as applied to a series of 6,153 deaths which occurred
      in a rural South African population from 1992 to 2005. We do not attempt to
      validate either approach in absolute terms. METHODS AND FINDINGS: The InterVA
      probabilistic model was applied to a series of 6,153 deaths which had previously
      been reviewed by physicians. Physicians used a total of 250 cause-of-death codes,
      many of which occurred very rarely, while the model used 33. Cause-specific
      mortality fractions, overall and for population subgroups, were derived from the
      model's output, and the physician causes coded into comparable categories. The
      ten highest-ranking causes accounted for 83% and 88% of all deaths by physician
      interpretation and probabilistic modelling respectively, and eight of the highest
      ten causes were common to both approaches. Top-ranking causes of death were
      classified by population subgroup and period, as done previously for the
      physician-interpreted material. Uncertainty around the cause(s) of individual
      deaths was recognised as an important concept that should be reflected in overall
      analyses. One notably discrepant group involved pulmonary tuberculosis as a cause
      of death in adults aged over 65, and these cases are discussed in more detail,
      but the group only accounted for 3.5% of overall deaths. CONCLUSIONS: There were
      no differences between physician interpretation and probabilistic modelling that
      might have led to substantially different public health policy conclusions at the
      population level. Physician interpretation was more nuanced than the model, for
      example in identifying cancers at particular sites, but did not capture the
      uncertainty associated with individual cases. Probabilistic modelling was
      substantially cheaper and faster, and completely internally consistent. Both
      approaches characterised the rise of HIV-related mortality in this population
      during the period observed, and reached similar findings on other major causes of
      mortality. For many purposes probabilistic modelling appears to be the best
      available means of moving from data on deaths to public health actions. Please
      see later in the article for the Editors' Summary.

PMID- 20808957
TI  - Rapid scaling up of insecticide-treated bed net coverage in Africa and its
      relationship with development assistance for health: a systematic synthesis of
      supply, distribution, and household survey data.
AB  - BACKGROUND: Development assistance for health (DAH) targeted at malaria has risen
      exponentially over the last 10 years, with a large fraction of these resources
      directed toward the distribution of insecticide-treated bed nets (ITNs).
      Identifying countries that have been successful in scaling up ITN coverage and
      understanding the role of DAH is critical for making progress in countries where
      coverage remains low. Sparse and inconsistent sources of data have prevented
      robust estimates of the coverage of ITNs over time. METHODS AND PRINCIPAL
      FINDINGS: We combined data from manufacturer reports of ITN deliveries to
      countries, National Malaria Control Program (NMCP) reports of ITNs distributed to
      health facilities and operational partners, and household survey data using
      Bayesian inference on a deterministic compartmental model of ITN distribution.
      For 44 countries in Africa, we calculated (1) ITN ownership coverage, defined as
      the proportion of households that own at least one ITN, and (2) ITN use in
      children under 5 coverage, defined as the proportion of children under the age of
      5 years who slept under an ITN. Using regression, we examined the relationship
      between cumulative DAH targeted at malaria between 2000 and 2008 and the change
      in national-level ITN coverage over the same time period. In 1999, assuming that
      all ITNs are owned and used in populations at risk of malaria, mean coverage of
      ITN ownership and use in children under 5 among populations at risk of malaria
      were 2.2% and 1.5%, respectively, and were uniformly low across all 44 countries.
      In 2003, coverage of ITN ownership and use in children under 5 was 5.1% (95%
      uncertainty interval 4.6% to 5.7%) and 3.7% (2.9% to 4.9%); in 2006 it was 17.5%
      (16.4% to 18.8%) and 12.9% (10.8% to 15.4%); and by 2008 it was 32.8% (31.4% to
      34.4%) and 26.6% (22.3% to 30.9%), respectively. In 2008, four countries had ITN
      ownership coverage of 80% or greater; six countries were between 60% and 80%;
      nine countries were between 40% and 60%; 12 countries were between 20% and 40%;
      and 13 countries had coverage below 20%. Excluding four outlier countries, each
      US$1 per capita in malaria DAH was associated with a significant increase in ITN
      household coverage and ITN use in children under 5 coverage of 5.3 percentage
      points (3.7 to 6.9) and 4.6 percentage points (2.5 to 6.7), respectively.
      CONCLUSIONS: Rapid increases in ITN coverage have occurred in some of the poorest
      countries, but coverage remains low in large populations at risk. DAH targeted at
      malaria can lead to improvements in ITN coverage; inadequate financing may be a
      reason for lack of progress in some countries. Please see later in the article
      for the Editors' Summary.

PMID- 20808958
TI  - Prox1 is required for granule cell maturation and intermediate progenitor
      maintenance during brain neurogenesis.
AB  - The dentate gyrus has an important role in learning and memory, and adult
      neurogenesis in the subgranular zone of the dentate gyrus may play a role in the
      acquisition of new memories. The homeobox gene Prox1 is expressed in the dentate
      gyrus during embryonic development and adult neurogenesis. Here we show that
      Prox1 is necessary for the maturation of granule cells in the dentate gyrus
      during development and for the maintenance of intermediate progenitors during
      adult neurogenesis. We also demonstrate that Prox1-expressing intermediate
      progenitors are required for adult neural stem cell self-maintenance in the
      subgranular zone; thus, we have identified a previously unknown non-cell
      autonomous regulatory feedback mechanism that controls adult neurogenesis in this
      region of the mammalian brain. Finally, we show that the ectopic expression of
      Prox1 induces premature differentiation of neural stem cells.

PMID- 20808959
TI  - piggybac- and PhiC31-mediated genetic transformation of the Asian tiger mosquito,
      Aedes albopictus (Skuse).
AB  - BACKGROUND: The Asian tiger mosquito, Aedes albopictus (Skuse), is a vector of
      several arboviruses including dengue and chikungunya. This highly invasive
      species originating from Southeast Asia has travelled the world in the last 30
      years and is now established in Europe, North and South America, Africa, the
      Middle East and the Caribbean. In the absence of vaccine or antiviral drugs,
      efficient mosquito control strategies are crucial. Conventional control methods
      have so far failed to control Ae. albopictus adequately. METHODOLOGY/PRINCIPAL
      FINDINGS: Germline transformation of Aedes albopictus was achieved by micro
      injection of embryos with a piggyBac-based transgene carrying a 3xP3-ECFP marker
      and an attP site, combined with piggyBac transposase mRNA and piggyBac helper
      plasmid. Five independent transgenic lines were established, corresponding to an
      estimated transformation efficiency of 2-3%. Three lines were re-injected with a
      second-phase plasmid carrying an attB site and a 3xP3-DsRed2 marker, combined
      with PhiC31 integrase mRNA. Successful site-specific integration was observed in
      all three lines with an estimated transformation efficiency of 2-6%.
      CONCLUSIONS/SIGNIFICANCE: Both piggybac- and site-specific PhiC31-mediated
      germline transformation of Aedes albopictus were successfully achieved. This is
      the first report of Ae. albopictus germline transformation and engineering, a key
      step towards studying and controlling this species using novel molecular
      techniques and genetic control strategies.

PMID- 20808960
TI  - Delta-like 4 differentially regulates murine CD4 T cell expansion via BMI1.
AB  - BACKGROUND: Studies have shown that Notch is essential for the maintenance of a T
      cell Th2 phenotype in vivo. It has also been shown that Notch ligands have
      diverse functions during T cell activation. We chose to investigate the role of
      Notch ligands during the Th2 response. PRINCIPAL FINDINGS: We studied the
      relationship of two Notch ligands, delta-like 4 and jagged-1, to T cell
      proliferation in C57 Bl/6 mice. Our findings indicate that jagged-1 does not
      affect the rate of T cell proliferation in any subset examined. However, delta
      like 4 causes an increase in the expansion of Th2 memory cells and a decrease in
      effector cell proliferation. Our in vivo studies indicate that the Notch system
      is dynamically regulated, and that blocking one Notch ligand increases the
      effective concentration of other Notch ligands, thus altering the response.
      Examination of genes related to the Notch pathway revealed that the Notch
      receptors were increased in memory T cells. Expression of BMI1, a gene involved
      in T cell proliferation, was also higher in memory T cells. Further experiments
      demonstrated that Notch directly regulates the expression of the BMI1 gene in T
      cells and may govern T cell proliferation through this pathway. CONCLUSIONS: From
      these experiments we can make several novel conclusions about the role of Notch
      ligands in T cell biology. The first is that delta-like 4 suppresses effector
      cell proliferation and enhances Th2 memory cell proliferation. The second is that
      blocking one Notch ligand in vivo effectively increases the concentration of
      other Notch ligands, which can then alter the response.

PMID- 20808961
TI  - Herbivore-specific, density-dependent induction of plant volatiles: honest or
      "cry wolf" signals?
AB  - Plants release volatile chemicals upon attack by herbivorous arthropods. They do
      so commonly in a dose-dependent manner: the more herbivores, the more volatiles
      released. The volatiles attract predatory arthropods and the amount determines
      the probability of predator response. We show that seedlings of a cabbage variety
      (Brassica oleracea var. capitata, cv Shikidori) also show such a response to the
      density of cabbage white (Pieris rapae) larvae and attract more (naive)
      parasitoids (Cotesia glomerata) when there are more herbivores on the plant.
      However, when attacked by diamondback moth (Plutella xylostella) larvae,
      seedlings of the same variety (cv Shikidori) release volatiles, the total amount
      of which is high and constant and thus independent of caterpillar density, and
      naive parasitoids (Cotesia vestalis) of diamondback moth larvae fail to
      discriminate herbivore-rich from herbivore-poor plants. In contrast, seedlings of
      another cabbage variety of B. oleracea (var. acephala: kale) respond in a dose
      dependent manner to the density of diamondback moth larvae and attract more
      parasitoids when there are more herbivores. Assuming these responses of the
      cabbage cultivars reflect behaviour of at least some genotypes of wild plants, we
      provide arguments why the behaviour of kale (B. oleracea var acephala) is best
      interpreted as an honest signaling strategy and that of cabbage cv Shikidori (B.
      oleracea var capitata) as a "cry wolf" signaling strategy, implying a conflict of
      interest between the plant and the enemies of its herbivores: the plant profits
      from being visited by the herbivore's enemies, but the latter would be better off
      by visiting other plants with more herbivores. If so, evolutionary theory on
      alarm signaling predicts consequences of major interest to students of plant
      protection, tritrophic systems and communication alike.

PMID- 20808962
TI  - Limited systemic sclerosis patients with pulmonary arterial hypertension show
      biomarkers of inflammation and vascular injury.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a common complication for
      individuals with limited systemic sclerosis (lSSc). The identification and
      characterization of biomarkers for lSSc-PAH should lead to less invasive
      screening, a better understanding of pathogenesis, and improved treatment.
      METHODS AND FINDINGS: Forty-nine PBMC samples were obtained from 21 lSSc subjects
      without PAH (lSSc-noPAH), 15 lSSc subjects with PAH (lSSc-PAH), and 10 healthy
      controls; three subjects provided PBMCs one year later. Genome-wide gene
      expression was measured for each sample. The levels of 89 cytokines were measured
      in serum from a subset of subjects by Multi-Analyte Profiling (MAP) immunoassays.
      Gene expression clearly distinguished lSSc samples from healthy controls, and
      separated lSSc-PAH from lSSc-NoPAH patients. Real-time quantitative PCR confirmed
      increased expression of 9 genes (ICAM1, IFNGR1, IL1B, IL13Ra1, JAK2, AIF1, CCR1,
      ALAS2, TIMP2) in lSSc-PAH patients. Increased circulating cytokine levels of
      inflammatory mediators such as TNF-alpha, IL1-beta, ICAM-1, and IL-6, and markers
      of vascular injury such as VCAM-1, VEGF, and von Willebrand Factor were found in
      lSSc-PAH subjects. CONCLUSIONS AND SIGNIFICANCE: The gene expression and cytokine
      profiles of lSSc-PAH patients suggest the presence of activated monocytes, and
      show markers of vascular injury and inflammation. These genes and factors could
      serve as biomarkers of PAH involvement in lSSc.

PMID- 20808963
TI  - Independent component analysis of the effect of L-dopa on fMRI of language
      processing.
AB  - L-dopa, which is a precursor for dopamine, acts to amplify strong signals, and
      dampen weak signals as suggested by previous studies. The effect of L-dopa has
      been demonstrated in language studies, suggesting restriction of the semantic
      network. In this study, we aimed to examine the effect of L-dopa on language
      processing with fMRI using Independent Component Analysis (ICA). Two types of
      language tasks (phonological and semantic categorization tasks) were tested under
      two drug conditions (placebo and L-dopa) in 16 healthy subjects. Probabilistic
      ICA (PICA), part of FSL, was implemented to generate Independent Components (IC)
      for each subject for the four conditions and the ICs were classified into task
      relevant source groups by a correlation threshold criterion. Our key findings
      include: (i) The highly task-relevant brain regions including the Left Inferior
      Frontal Gyrus (LIFG), Left Fusiform Gyrus (LFUS), Left Parietal lobe (LPAR) and
      Superior Temporal Gyrus (STG) were activated with both L-dopa and placebo for
      both tasks, and (ii) as compared to placebo, L-dopa was associated with increased
      activity in posterior regions, including the superior temporal area (BA 22), and
      decreased activity in the thalamus (pulvinar) and inferior frontal gyrus (BA
      11/47) for both tasks. These results raise the possibility that L-dopa may exert
      an indirect effect on posterior regions mediated by the thalamus (pulvinar).

PMID- 20808965
TI  - The long-term safety and efficacy of opioids: a survey of 84 selected patients
      with intractable chronic noncancer pain.
AB  - BACKGROUND: The use of opioids for chronic noncancer pain (CNCP) remains
      controversial. Despite a number of randomized controlled trials showing efficacy
      and safety in the short term, long-term data are limited. OBJECTIVE: To survey a
      selected cohort of patients with intractable CNCP with regard to long-term
      efficacy and safety of opioids. METHODS: The present study reports long-term
      results from a survey of 84 patients with CNCP. The majority of patients had
      neuropathic pain, were treated with opioids and were followed every three months
      for a median of 8.4 years. Outcomes examined were pain severity, adverse effects,
      pain relief, satisfaction, mood, problematic opioid use, tolerance, physical
      dependency, functional status, health-related quality of life, immune status,
      sexual function, morbidity and mortality. Measures included a numerical rating
      scale, the Hospital Anxiety and Depression Scale, Brief Pain Inventory
      interference scale, Pain Disability Index and Short-Form Health Survey 12,
      version 2. RESULTS AND CONCLUSIONS: Both long- and short-acting opioids were
      reported to be effective, with few significant long-term adverse effects in many
      subjects in the present selected cohort. The majority of patients reported at
      least 50% or greater pain relief and a moderate improvement in disability.
      Functional status and health-related quality of life scores were not severely
      affected. Problematic opioid use, tolerance and serious adverse effects,
      including constipation, were not major issues. The authors emphasize that the
      results obtained in the present selected group may not be generalizable to all
      CNCP patients in whom opioids are being initiated.

PMID- 20808966
TI  - Posterior interscalene block: an ultrasound-guided case series and overview of
      history, anatomy and techniques.
AB  - BACKGROUND: The posterior interscalene block has been described as an alternative
      to the lateral interscalene block. However, this technique has not gained
      popularity because of the close proximity of the approach to vascular and central
      neural structures. OBJECTIVE: To describe the posterior interscalene block
      technique using ultrasound imaging, and to review the history of its evolution.
      METHODS: The use of ultrasound imaging to facilitate the insertion of
      interscalene catheters using the posterior approach in 11 patients undergoing
      total shoulder arthroplasty is described. RESULTS: All 11 patients had
      satisfactory analgesia in the first 24 h of the postoperative period. None of the
      patients complained of neck pain, as had been found in earlier techniques using
      the posterior approach. CONCLUSIONS: This modification of the posterior approach
      is a safe and effective method for the insertion of interscalene brachial plexus
      catheters. These catheters are also comfortable for patients and, in the present
      study, none of the catheters inadvertently fell out.

PMID- 20808967
TI  - Quantifying the pain experience in hip and knee osteoarthritis.
AB  - PURPOSE: The present study investigated whether the conceptualization of hip and
      knee osteoarthritis pain implicit in the Western Ontario and McMaster
      Universities Arthritis Index (WOMAC) and Medical Outcomes Study Short-Form 36 (SF
      36) scales is complete, or whether the addition of another scale, such as the
      Short-Form McGill Pain Questionnaire (MPQ-SF), provides a more complete
      characterization. Furthermore, the impact that mental health symptoms and
      catastrophizing had on these scales was investigated. METHODS: Before hip and
      knee arthroplasty, 200 patients completed surveys of demographic data, the WOMAC
      pain scale, the MPQ-SF, the SF-36 Bodily Pain scale, the Pain Catastrophizing
      Scale and the Hospital Anxiety and Depression Scale. Correlations between scales
      were calculated and linear regression modelling was used to determine the impact
      of mental health and catastrophizing on these three pain measures. RESULTS: A
      strong correlation between the WOMAC and SF-36 pain scales (r=-0.70) was found;
      however, both correlated only moderately with the MPQ-SF (r=0.36 and r=-0.36,
      respectively). Linear regression modelling showed that the Pain Catastrophizing
      Scale significantly predicted a greater score on all three pain scales (P<0.05).
      CONCLUSIONS: The addition of the MPQ-SF appears to add to a more complete
      quantification of the pain experience in hip and knee osteoarthritis.

PMID- 20808968
TI  - Attentional and emotional mechanisms of pain processing and their related
      factors: a structural equations approach.
AB  - BACKGROUND/OBJECTIVE: It is known that maladaptive attentional and emotional
      mechanisms of pain processing - as indicated by constructs such as pain
      hypervigilance, pain-related anxiety and pain catastrophizing - play an important
      role in the development and maintenance of chronic pain conditions. However,
      little is known to date about the potential risk factors for these forms of
      maladaptive processing. The aim of the present study was to shed more light on
      this issue. A very comprehensive set of predictor variables was examined in
      healthy pain-free subjects. METHOD: Participants were 92 young and healthy
      subjects (mean [+/- SD] age 26.99+/-6.90 years; 47 men, 45 women). Maladaptive
      attentional and emotional mechanisms of pain processing were assessed by self
      report measures of pain hypervigilance, pain-related anxiety and pain
      catastrophizing, as well as by a dot-probe task. The comprehensive set of
      predictor variables included measures of affective and bodily distress
      (depression, anxiety and somatization), experimental pain sensitivity, and
      cortisol reactivity. Directed relationships were estimated by using structural
      equation modelling. RESULTS: Structural equation modelling revealed a significant
      path from affective and bodily distress to self-reported maladaptive attentional
      and emotional pain processing. In contrast, the paths from pain sensitivity and
      cortisol reactivity did not reach the level of significance. CONCLUSION: These
      results support the position that anxiety and depression, as well as
      somatization, contribute to the aberrance of attentional and emotional mechanisms
      of pain processing. Surprisingly, the assumption of a close relationship between
      these maladaptive mechanisms of pain processing and pain sensitivity could not be
      confirmed.

PMID- 20808969
TI  - Cognitive and school functioning in children and adolescents with chronic pain: a
      critical review.
AB  - Cognitive function is a critical factor related to a child's overall
      developmental trajectory. There is increasing evidence that chronic pain disrupts
      cognitive function in adults. Little is known about the nature or impact of
      cognitive disruption in children and adolescents with chronic pain. The present
      review examines the current literature related to cognitive function in children
      and adolescents with chronic pain, implications of these findings and future
      research directions. Nine studies on this topic were found, with a relatively
      recent increase in publications related to school attendance and subjective
      studies of school performance. The studies that were found on this topic
      suggested that chronic pain affects cognitive function in children but the scope
      of these effects on children's function and developmental trajectories is not yet
      clear. While methodological issues surely make it difficult to study cognitive
      function in children with chronic pain, the potential gains from such research
      warrant a pursuit of such work. Much remains to be studied on this important
      topic.

PMID- 20808970
TI  - [Autism and pain - a literature review].
AB  - The purpose of the present article was to assess the available literature
      concerning pain and autism. First, authors summarized the published articles on
      pain reactivity in people with autism. Second, the hypotheses envisaged to
      explain the presence of expressive particularities in people with autism spectrum
      disorders were reviewed; these included endogenous opioid excess theory,
      sensorial abnormalities and sociocommunicative deficit. Finally, the present
      review dealt with the tools available to assess and manage pain in people with
      autism. In conclusion, the authors revealed the need for more research to obtain
      more consensual data and provided some recommendations in this domain that were
      under exploited by the scientific community. From a clinical point of view, more
      knowledge about pain in people with autism should enable the development of
      specific assessment tools and, consequently, better pain management in daily
      care.

PMID- 20808973
TI  - Optimizing pulmonary rehabilitation in chronic obstructive pulmonary disease-
      practical issues: a Canadian Thoracic Society Clinical Practice Guideline.
AB  - Pulmonary rehabilitation (PR) participation is the standard of care for patients
      with chronic obstructive pulmonary disease (COPD) who remain symptomatic despite
      bronchodilator therapies. However, there are questions about specific aspects of
      PR programming including optimal site of rehabilitation delivery, components of
      rehabilitation programming, duration of rehabilitation, target populations and
      timing of rehabilitation. The present document was compiled to specifically
      address these important clinical issues, using an evidence-based, systematic
      review process led by a representative interprofessional panel of experts. The
      evidence reveals there are no differences in major patient-related outcomes of PR
      between nonhospital- (community or home sites) or hospital-based sites. There is
      strong support to recommend that COPD patients initiate PR within one month
      following an acute exacerbation due to benefits of improved dyspnea, exercise
      tolerance and health-related quality of life relative to usual care. Moreover,
      the benefits of PR are evident in both men and women, and in patients with
      moderate, severe and very severe COPD. The current review also suggests that
      longer PR programs, beyond six to eight weeks duration, be provided for COPD
      patients, and that while aerobic training is the foundation of PR, endurance and
      functional ability may be further improved with both aerobic and resistance
      training.

PMID- 20808974
TI  - Postal code diagnosis and treatment of sleep apnea.

PMID- 20808975
TI  - Wait times for sleep apnea care in Ontario: a multidisciplinary assessment.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a highly prevalent disorder that is
      associated with significant patient morbidity and societal burden. In general,
      wait times for health care in Ontario are believed to be lengthy; however, many
      diseases lack specific corroborative wait time data. OBJECTIVE: To characterize
      wait times for OSA care in Ontario. METHODS: Cross-sectional survey. A survey
      tool was designed and validated to question physicians involved in OSA care about
      the length of the wait times their patients experience while traversing a
      simplified model of OSA care. The survey was sent to all otolaryngologists and
      respirologists in the province, as well as to a random sample of provincial
      family physicians. RESULTS: Patients waited a mean of 11.6 months to initiate
      medical therapy (continuous positive airway pressure), and 16.2 months to
      initiate surgical therapy. Sleep laboratory availability appeared to be the major
      restriction in the patient management continuum, with each additional sleep
      laboratory in a community associated with a 20% decrease in overall wait times.
      Smaller community sizes were paradoxically associated with shorter wait times for
      sleep studies (P<0.01) but longer wait times for OSA surgery (P<0.05). Regression
      analysis yielded an r2 of 0.046; less than 5% of the wait time variance could be
      explained by the simplified model. CONCLUSION: Patients experienced considerable
      wait times when undergoing management for OSA. This has implications for both
      individual patient care and public health in general.

PMID- 20808976
TI  - Adherence to pediatric asthma guidelines in the emergency department: a survey of
      knowledge, attitudes and behaviour among health care professionals.
AB  - BACKGROUND: Despite strong evidence for using clinical care pathways to manage
      acute pediatric asthma, adherence remains suboptimal. OBJECTIVES: To elicit
      information from health care professionals regarding their knowledge, attitudes
      and use of a care pathway for acute childhood asthma. METHODS: A cross-sectional,
      self-administered survey of physicians, nurses and respiratory therapists who
      worked in the emergency department at the Montreal Children's Hospital (Montreal,
      Quebec) from August to December 2007 was conducted. The survey assessed
      knowledge, attitude toward and agreement with the care pathway, as well as its
      use four years after its implementation. RESULTS: Of the 128 health care
      professionals surveyed, 72 (56%) responded. Of these, 99% reported being familiar
      with the pathway, more than 90% agreed with its use for mild and moderate asthma,
      while 79% agreed with its use for severe asthma. For 99% of health care
      professionals, the advantages of using the pathway outweighed the disadvantages;
      however, 64% admitted to making variations to the pathway. Although 92% of
      respondents reported that they were quite comfortable with using the asthma
      severity Pediatric Respiratory Assessment Measure, only 53% and 36% correctly
      identified the severity score cut-offs for moderate and severe asthma,
      respectively. Seventeen per cent of respondents underestimated the delay of onset
      of action of oral corticosteroids, while 36% of physicians incorrectly believed
      that a higher than necessary dose was recommended for ipratropium bromide.
      CONCLUSIONS: Results of the survey confirmed that the health care professionals
      queried had a positive attitude toward the pediatric asthma care pathway.
      Knowledge gaps and the balance between standardization versus individualization
      of care may be key elements to explain suboptimal adherence to the pathway.

PMID- 20808977
TI  - Use of complementary and alternative medicine in children with asthma.
AB  - BACKGROUND: Because of the potential risk of interaction with, and underuse of,
      conventional medications, it is important to document the prevalence of the use
      of complementary and alternative medicines (CAMs) in asthmatic children.
      OBJECTIVE: To ascertain the prevalence and type of CAMs, and to identify factors
      associated with their use. METHODS: A cross-sectional survey of children who
      presented to the Asthma Centre of The Montreal Children's Hospital (Montreal,
      Quebec) between 1999 and 2007 was conducted. At the initial consultation, parents
      completed a questionnaire inquiring, in part, about CAM use. Computerized health
      records provided information regarding patient characteristics and their
      condition. RESULTS: The median age of the 2027 children surveyed was 6.1 years
      (interquartile range 3.3 to 10.5 years); 58% were male and 59% of children had
      persistent asthma. The prevalence of CAM use was 13% (95% CI 12% to 15%).
      Supplemental vitamins (24%), homeopathy (18%) and acupuncture (11%) were the most
      commonly reported CAMs. Multivariable logistic regression analysis confirmed the
      association of CAM use with age younger than six years (OR 1.86; 95% CI 1.20 to
      2.96), Asian ethnicity (OR 1.89; 95% CI 1.01 to 3.52), episodic asthma (OR 1.88;
      95% CI 1.08 to 3.28) and poor asthma control (OR 1.98; 95% CI 1.80 to 3.31).
      CONCLUSION: The prevalence of reported CAM use among Quebec children with asthma
      remained modest (13%), with vitamins, homeopathy and acupuncture being the most
      popular modalities. CAM use was associated with preschool age, Asian ethnicity,
      episodic asthma and poor asthma control.

PMID- 20808978
TI  - Induced sputum for the diagnosis of pulmonary tuberculosis: Is it useful in
      clinical practice?
AB  - BACKGROUND: Diagnosing pulmonary tuberculosis (PTB) is challenging in patients
      who are unable to spontaneously expectorate. Published evidence suggests that
      induced sputum (IS) is the least invasive and most cost-effective method of
      diagnosis, and should be used before fibre-optic bronchoscopy (FOB). METHODS: The
      medical records of 337 adults treated for PTB in northern Alberta between 1997
      and 2007 were reviewed to determine whether local practice patterns reflect the
      evidence. Microbiological data were collected from the Provincial Laboratory for
      Public Health. Demographic information was collected from the patients' charts.
      RESULTS: A total of 8.5% (26 of 307) of PTB patients had IS collected, whereas
      35.8% (110 of 307) underwent FOB. Among FOB patients, 56.4% (62 of 110) had no
      sputum sent before the procedure and 29% (18 of 62) of these patients were smear
      positive. Only five patients referred for FOB had IS sent previously. There were
      no demographic factors predictive of IS use, whereas being an inpatient at a
      teaching facility or having a nodule or mass on chest x-ray was predictive of FOB
      referral. Because so few IS samples were available, not all patients had
      spontaneously expectorated sputum, IS and FOB tests performed; thus, the
      calculated yields were not comparable with one another. CONCLUSIONS: Despite
      published evidence recommending IS collection before FOB referral in suspected
      PTB patients, clinicians in our health region appeared to prefer early FOB over
      IS by a large margin. This practice pattern is less cost effective and exposes
      patients and health care workers to greater risk. Further research is needed to
      identify the reasons for the underuse of sputum induction.

PMID- 20808980
TI  - A patient with an aberrant pulmonary blood supply and recurrent infection.
AB  - A case of intralobar pulmonary sequestration presenting with recurrent episodes
      of infection is reported. Pulmonary sequestration is a rare congenital
      malformation characterized by accessory lung tissue with no direct connection to
      the tracheobronchial tree and is supplied by an aberrant systemic artery. The
      aberrant artery is key to both diagnosis and treatment. The correct diagnosis may
      be suspected on clinical grounds and should be confirmed by identifying the
      lesion and aberrant artery on imaging studies. Surgical resection is curative,
      taking particular care not to injure the aberrant artery, which may result in
      devastating intraoperative hemorrhage.

PMID- 20808981
TI  - Lung atelectasis secondary to massive esophageal dilation in a patient with
      scleroderma.
AB  - Esophageal dilation is a rare complication of scleroderma and CREST syndrome. A
      case of atelectasis secondary to right inferior bronchus compression by a
      massively dilated esophagus is described. The authors are unaware of any previous
      cases of atelectasis secondary to esophageal dilation in scleroderma.

PMID- 20808979
TI  - Airway remodelling in asthma: from benchside to clinical practice.
AB  - Airway remodelling refers to the structural changes that occur in both large and
      small airways relevant to miscellaneous diseases including asthma. In asthma,
      airway structural changes include subepithelial fibrosis, increased smooth muscle
      mass, gland enlargement, neovascularization and epithelial alterations. Although
      controversial, airway remodelling is commonly attributed to an underlying chronic
      inflammatory process. These remodelling changes contribute to thickening of
      airway walls and, consequently, lead to airway narrowing, bronchial hyper
      responsiveness, airway edema and mucous hypersecretion. Airway remodelling is
      associated with poor clinical outcomes among asthmatic patients. Early diagnosis
      and prevention of airway remodelling has the potential to decrease disease
      severity, improve control and prevent disease expression. The relationship
      between structural changes and clinical and functional abnormalities clearly
      deserves further investigation. The present review briefly describes the
      characteristic features of airway remodelling observed in asthma, its clinical
      consequences and relevance for physicians, and its modulation by therapeutic
      approaches used in the treatment of asthmatic patients.

PMID- 20808982
TI  - Medical radiation exposure and accidents. Dosimetry and radiation protection. Do
      we only benefit the patient?
AB  - This article presents and discusses new information on the old Hippocratic moto
      of "...not to harm but to benefit the patient". Some radiation accidents are due
      to medical errors. Millions of medical tests exposing radiation are performed
      every day worldwide increasing and sometimes exceeding the annual permissible
      dose administered to the general population. Public authorities are now seriously
      concerned about medical radiation overused. In U.S.A. both the House of
      Representatives and the Food and Drug Administration have recently delt with this
      problem. Others and we have suggested before and the International Atomic Energy
      Agency now proposes: a "Smart Card" for every individual who receives medical
      radiation. In this card the amount of medical radiation administered will be
      recorded. It is time to issue rules for protection of the public from medical
      radiation overdose.

PMID- 20808983
TI  - The philosophic and biological views of the "atomic" philosophers, Leucippus and
      Democritus.
AB  - The purpose of this study was to describe and highlight the work of the so called
      "atomic" philosophers Leucippus and in particular, his student Democritus, after
      an extensive research of works written by numerous ancient Greek philosophers and
      historians. The work of these two philosophers is groundbreaking, covers a wide
      spectrum of science and humanities and shows their high level of scholarship,
      erudition, and analytical thinking. Their ideas are often mentioned by other
      ancient Greek philosophers, with positive and sometimes negative criticism. Their
      theories were spread later, in ancient Rome, Byzantium, the Medieval Western
      Europe and in our times.

PMID- 20808984
TI  - Resting electrocardiogram and stress myocardial perfusion imaging in the
      determination of left ventricular systolic function: an assessment enhancing the
      performance of gated SPET.
AB  - This study aimed to determine systolic dysfunction and estimate resting left
      ventricular ejection fraction (LVEF) from information collected during routine
      evaluation of patients with suspected or known coronary heart disease. This
      approach was then compared to gated single photon emission tomography (SPET).
      Patients having undergone stress (201)Tl myocardial perfusion imaging followed by
      equilibrium radionuclide angiography (ERNA) were separated into derivation
      (n=954) and validation (n=309) groups. Logistic regression analysis was used to
      develop scoring systems, containing clinical, electrocardiographic (ECG) and
      scintigraphic data, for the discrimination of an ERNA-LVEF<0.50. Linear
      regression analysis provided equations predicting ERNA-LVEF from those scores. In
      373 patients LVEF was also assessed with (201)Tl gated SPET. Our results showed
      that an ECG-Scintigraphic scoring system was the best simple predictor of an ERNA
      LVEF<0.50 in comparison to other models including ECG, clinical and scintigraphic
      variables in both the derivation and validation subpopulations. A simple linear
      equation was derived also for the assessment of resting LVEF from the ECG
      Scintigraphic model. Equilibrium radionuclide angiography-LVEF had a good
      correlation with the ECG-Scintigraphic model LVEF (r=0.716, P=0.000), (201)Tl
      gated SPET LVEF (r=0.711, P=0.000) and the average LVEF from those assessments
      (r=0.796, P=0.000). The Bland-Altman statistic (mean+/-2SD) provided values of
      0.001+/-0.176, 0.071+/-0.196 and 0.040+/-0.152, respectively. The average LVEF
      was a better discriminator of systolic dysfunction than gated SPET-LVEF in
      receiver operating characteristic (ROC) analysis and identified more patients
      (89%) with a </=10% difference from ERNA-LVEF than gated SPET (65%, P=0.000). In
      conclusion, resting left ventricular systolic dysfunction can be determined
      effectively from simple resting ECG and stress myocardial perfusion imaging
      variables. This model provides reliable LVEF estimations, comparable to those
      from (201)Tl gated SPET, and can enhance the clinical performance of the latter.

PMID- 20808985
TI  - The value of different washout parameters in the evaluation of renal transplants
      by technetium-99m-ethylene- l-l-dicysteine.
AB  - Technetium-99m-ethylene-l-l-dicysteine ((99m)Tc-EC) is an agent with a potential
      for renal imaging. It is reported that EC uses the same tubular transporter
      system as ortho-hippurate (OIH) and mercaptoacetyltriglycine (MAG3) and that this
      agent has good imaging properties and higher renal clearance than MAG3. In this
      study we used (99m)Tc-EC to compare different washout parameters in renal
      transplanted patients. Sixty nine scans in 55 patients (38 males, 17 females)
      were performed with (99m)Tc-EC during the follow-up period after kidney
      transplantation. After bolus injection of 280MBq (99m)Tc-EC, 60x1sec and 29x1min
      images were taken in anterior position. Perfusions of transplanted kidneys were
      examined visually and perfusion indices (PI) were calculated according to
      Hilson's method. The semiquantitative washout parameters such as 20 and 30min to
      peak activity ratios and 20 and 30min to 3min activity ratios were calculated.
      The patients were clinically evaluated by nephrologists experienced in renal
      transplantation cases and followed-up by serum creatinine and blood urea nitrogen
      determinants which were checked every postoperative day until stabilized to a
      optimal level for each patient. Two standard deviations above the mean values
      derived from all cases with normal functioning transplanted kidneys were
      calculated for each method. Then, these values served as the threshold to
      differentiate the pathological cases respectively. Of the 69 total studies
      performed, we found 34 normal kidneys, 14 rejections, 19 acute tubular necrosis
      (ATN) and 2 cyclosporin A toxicity cases. The number of abnormal cases detected
      with 30/3min, 30/max, 20/3min and 20/max indices were 27, 26, 24, and 18,
      respectively. In conclusion, we strongly recommend in studying renal transplants
      to consider the activity at the 3(rd) min post injection as a reference point
      instead of the time to maximum activity for washout index calculation. If, for
      any reason the time to maximum counts using (99m)Tc-(peak activity) is prefered,
      then the period of study should not be performed for less than 30min to achieve
      reliable results.

PMID- 20808986
TI  - Contribution of radioiodine uptake measurement and thyroid scintigraphy to the
      differential diagnosis of thyrotoxicosis.
AB  - Both clinical and subclinical thyrotoxicosis can result from a wide range of
      disorders. Establishing the correct etiology underlying thyrotoxicosis is
      essential to direct treatment towards its specific pathophysiologic process.
      Based on clinical experience and guideline recommendations, radioiodine iodine
      uptake (RAIU) measurement and scintigraphy are often requested as the first-line
      investigation in thyrotoxic patients; however, their specific individual
      contribution to the differential diagnosis of thyrotoxicosis has not been
      previously investigated. In our study we aimed at evaluating the diagnostic role
      of RAIU measurement and scintigraphy in the management of thyrotoxicosis. A total
      of 108 patients with clinical and 42 patients with subclinical thyrotoxicosis
      were included in this retrospective study. All patients had RAIU measured at 24
      hours after (131)I-iodide administration, followed by thyroid scintigraphy. Based
      on the combination of RAIU and scintigraphy, patients were classified as having
      diffuse toxic goiter (DTG) in 44% (the most common diagnosis), toxic adenoma in
      15.9%, thyroiditis in 14%, and toxic multinodular goiter in 2.7%, while the
      pattern was inconclusive in 22.7% of all patients. When considering only patients
      with clinical thyrotoxicosis, the scan was inconclusive in 12.9% of patients
      whereas it was inconclusive in 47.6% of patients with subclinical thyrotoxicosis.
      There was a highly significant association between thyrotoxic status and scan
      result, with a statistically significant better performance of RAIU and
      scintigraphy in patients with clinical thyrotoxicosis when compared to patients
      with subclinical thyrotoxicosis considered as a whole (P<0.001). Instead, no
      statistically significant difference was observed between patients with
      subclinical thyrotoxicosis and TSH <0.1 mU/L and patients with TSH between 0.1
      mU/L and 0.4 mU/L (P=0.191). In conclusion, we confirm the key role of RAIU and
      scintigraphy in the management of thyrotoxicosis and document its better
      performance in patients with clinical thyrotoxic status.

PMID- 20808987
TI  - Cerebral blood flow and cognitive function in obstructive sleep apnea syndrome.
AB  - Neuropsychological deficits are among the main symptoms of obstructive sleep
      apnea syndrome (OSAS), which could be related to impaired cerebral blood flow
      (CBF). We conducted a study in 20 subjects tested in our Sleep Laboratory, to
      assess regional CBF and cognitive function in OSAS. Our measurements included
      technetium-99m hexamethylamino propylenamine oxime brain perfusion scintigraphy
      in wakeful state, i.e. in the morning after polysomnography and also cognitive
      function tests after polysomnography, in 20 patients, 16 male and 4 female, aging
      between 30 and 60 years. We found that apnea-hypopnea index was greater than or
      equal to 5 in 16 (85%) subjects, consistent with OSAS. Mean arterial oxygen
      saturation during sleep was correlated with CBF in all regions. Cognitive
      function test scores in verbal memory were positively correlated with percentage
      of sleep duration with less than 90% of oxygen saturation during sleep. Cerebral
      blood flow was not uniform in OSAS patients, and was significantly lower in the
      left frontal and left temporal regions as compared to that of these regions on
      the right hemisphere. In conclusion, our findings indicated association of CBF
      and verbal memory with hypoxemia during sleep and decreased perfusion after
      apneic episodes in the left frontal and temporal lobes in OSAS patients, which
      could also indicate impairment of upper airway motor control.

PMID- 20808988
TI  - The efficacy of (99m)Tc-MIBI scintimammography in the evaluation of breast
      lesions and axillary involvement: a comparison with X-rays mammography,
      ultrasonography and magnetic resonance imaging.
AB  - This study was performed because the efficacy of technetium-99m methoxyisobutyl
      isonitrile scintimammography ((99m)Tc-MIBI-SM) in the evaluation of the breast
      lesions and axillary lymph node involvement in comparison with X-rays mammography
      (XRM), ultrasonography (US) and magnetic resonance imaging (MRI) has not been
      fully investigated. Forty six female patients were included in this study, with
      suspicious lesions detected in their breasts by palpation, by imaging modalities
      or clinically. All patients underwent (99m)Tc-MIBI-SM, US and MRI for the
      evaluation of breast lesions. All patients according to clinical situation and
      imaging studies underwent fine needle aspiration, mass extirpation, core biopsy,
      modified radical mastectomy or partial lumpectomy in order to confirm the nature
      of the lesions. Our results showed that (99m)Tc-MIBI-SM detected 15 of 16, US 11
      of 16, XRM 13 of 16 and MRI 13 of 16 malignant lesions. Sensitivities were 93%,
      68%, 81% and 81%, respectively. Among these cases there were 4 of 15 false
      positive (FP) results on SM whereas 4 of 11 on US, 11 of 13 on XRM and 8 of 13 on
      MRI. The specificities of the above modalities were 86%, 87%, 63% and 73%,
      respectively. The sensitivities of the above imaging modalities for the detection
      of axillary lymph node metastases were 55%, 55%, 11% and 77% for SM, US, XRM and
      MRI, respectively. The sensitivity and specificity of SM for the palpable lesions
      (n=31) were 100% and 84% and for the nonpalpable lesions (n=15) were 75% and 90%,
      respectively. In conclusion, although the number of patients studied was small it
      is the opinion of the authors that (99m)Tc-MIBI-SM has a much better sensitivity
      and less FP results in detecting malignant breast lesions than the other 3
      modalities and also better sensitivity than XRM and MRI. Thus (99m)Tc-MIBI-SM can
      be included in the diagnostic algorithms for detecting malignancy in breast
      tumors.

PMID- 20808989
TI  - The role of nuclear medicine in the diagnosis of common and specific diabetic
      infections.
AB  - Infections are usually detected in diabetes mellitus. They may be divided into:
      common infections such as fungal infections, pulmonary tuberculosis, pneumonia,
      bacteraemia, urinary tract infections, and diabetic foot infections and specific
      infections. The latter occur almost exclusively in diabetes and include
      rhinocerebral mucormycosis, malignant external otitis, emphysematous
      pyelonephritis, perirenal abscess, emphysematous cystitis and emphysematous
      cholecystitis. Radionuclide tests are decisive in the diagnosis and localisation
      of foot osteomyelitis, as well as the distinction of osteomyelitis from other
      conditions, notably Charcot osteoarthropathy. Technetium-99m methylene
      disphosphonate and labelled leukocyte bone scans are the main imaging techniques
      employed, while emerging techniques include single-photon emission
      tomography/computed tomography (CT) and positron emission tomography/CT. Nuclear
      medicine is also useful in the diagnosis and follow-up of specific infections in
      diabetes like, malignant external otitis, rhinocerebral mucormycosis, acute
      pyelonephritis, renal papillary necrosis and cholecystitis. The main indications
      of nuclear medicine tests are diabetic foot osteomyelitis, malignant external
      otitis, rhinocerebral mucormycosis and renal infections.

PMID- 20808990
TI  - Somatostatin receptor imaging with (111)In-pentetreotide in gastro-intestinal
      tract and lung neuroendocrine tumors-Impact on targeted treatment.
AB  - Somatostatin is a neuropeptide that confers a wide range of pharmacological
      properties. Indium-111-tagged pentetreotide ((111)In-P) is a radiolabeled
      analogue of somatostatin indicated for the in vivo scintigraphic localization of
      neuroendocrine tumors (NET). In cases of NET of the gastro-intestinal tract we
      describe the sensitivity compared to conventional anatomical imaging modalities
      and especially the possibility that (111)In-P may change therapeutic management
      into up one fourth of the patients. In cases of small cell lung carcinoma it has
      been used for the evaluation of somatostatin receptor status and a substantial
      tool for differentiation between limited and extensive disease, especially when
      combined with anatomical imaging methods. We also describe the radiolabeled with
      yttrium-90 or lutetium-177 somatostatin analogue peptides in the treatment of NET
      and also the use of (111)In-P for the selection of patients for targeted
      treatment.

PMID- 20808991
TI  - Novel use of hepatobiliary scintigraphy for the diagnosis of interleukin-2
      cholangiopathy.
AB  - We report a case of interleukin-2 (IL-2) induced cholangiopathy diagnosed with
      the aid of hepatobiliary scintigraphy. Patient was a 32 years old, male with
      history of metastatic melanoma. Computed tomography (CT) upon admission
      demonstrated worsening of patient's metastatic lung disease with a normal
      appearance of the gallbladder. The patient was started on high dose IL-2
      treatment for regression of his disease. Four days after IL-2 treatment was
      begun, the patient developed severe right upper quadrant pain and elevated liver
      function tests. A right upper quadrant ultrasound and surgical consultation were
      requested. Sonographic findings demonstrated diffuse gallbladder wall thickening,
      mural edema, a positive sonographic Murphy's sign, but no gallstones. The
      preliminary working diagnosis was acalculous cholecystitis versus IL-2 induced
      cholangiopathy. To clarify between these two entities, a hepatobiliary scan was
      obtained that demonstrated filling of the gallbladder with prompt biliary-to
      bowel transit and normal liver function. In this case, the clinical presentation
      and history of recent IL-2 treatment were suggestive of IL-2 cholangiopathy,
      though the patient's co-morbidities and in-patient status raised concern for
      acalculous cholecystitis. Given the marked differences in treatment,
      hepatobiliary imaging was requested and found to be normal, making acalculous
      cholecystitis very unlikely. In conclusion, we believe this is the first case in
      which hepatobiliary scintigraphy was used to aid in the diagnosis of IL-2 induced
      cholangiopathy.

PMID- 20808992
TI  - (18)F-FDG-PET/CT findings in patients affected by spondylodiscitis.
AB  - Spondylodiscitis (SPD) is an inflammatory process of the intervertebral disc
      space. We report two cases of patients affected by SPD evaluated by fluorine-18
      fluorodesoxyglycose positron emission tomography/computed tomography, which was
      useful in detecting SPD and supporting differential diagnosis.

PMID- 20808993
TI  - Incidental detection of skeletal metastases from thyroid cancer during myocardial
      perfusion imaging.

PMID- 20808994
TI  - Incidental detection of pseudodiverticulum of sigmoid colon on (18)F-FDG-PET/CT
      in a patient with lymphoma.

PMID- 20808995
TI  - An original case of lip metastasis, from non small cell lung cancer.

PMID- 20808996
TI  - Negative effect of intravenous immunoglobulin administration on the scintiscans
      to identify accessory spleen in an idiopathic thrombocytopenic purpura patient.

PMID- 20808997
TI  - Incidental congenital renal and ureteric anomalies in patients studied for
      neoplastic diseases.

PMID- 20808998
TI  - False positive (18)F-FDG-PET/CT findings in a patient with talc pleurodesis.

PMID- 20808999
TI  - Technetium-99m HMPAO brain SPET findings of Dyke-Davidoff-Masson syndrome.

PMID- 20809000
TI  - [Cancer, environment, radiation and nuclear medicine].
AB  - Today, although science and technology have greatly developed, cancer is still
      under the shadow of prejudice and considered as a death sentence. As for who is
      to blame for this situation, we should not forget the actual influence of
      natural, technical and social environment in which we all live and offer or
      receive various forms of energy. Various kinds of radiation including radiation
      from the sun are found in our natural environment and radiation from the sun
      contributes especially to the development of melanoma. In our social environment
      we tend to develop harmful habits such as smoking and alcohol drinking, to have
      insufficient physical exercise and increased body weight. All these habits are
      concidered potentially carcinogenic. A new branch of medicine, which also tries
      to diagnose and treat cancer has been created lately. This is the speciality of
      Nuclear Medicine which has developed since 1945. This new specialty, aided by
      modern equipment has many useful diagnostic and therapeutic applications against
      cancer as mentioned in this lecture.

PMID- 20809001
TI  - [Cutaneous melanoma; diagnostic procedures and their evaluation in diagnosing and
      mapping sentinel nodes. Part 2].
AB  - The second part of this review describes the advantages, and evaluates the
      radionuclide-guided methods for sentinel lymph node localization and also
      evaluates the intraoperative application of the blue dye technique in melanoma.
      By combining the two techniques, the detection rate rises to 96%-98%. The
      presence of cancer cells in the sentinel node is histopathologically shown by
      using hematoxylin-eosin and by using sensitive techniques for the detection of
      micrometastases. Immunohistochemical tech-niques specific for epithelial markers
      and polymerase chain reaction examination are also applied. Sentinel lymph node
      biopsy suggests whether regional elective lymphade-nectomy shall be performed.

PMID- 20809015
TI  - Prostate lesions with cribriform / pseudocribriform pattern.
AB  - Prostate lesions with cribriform / pseudocribriform architecture range from
      normal histological structures to infiltrative carcinoma. In each group of
      lesions with cribriform architecture (benign, premalignant and malignant
      intraductal or infiltrating), there are situations in which histological
      classification of the lesion is difficult or impossible on routine stains. A more
      wide-scale application of the immunohistochemical investigation for clearing up
      the problematic prostate lesions led to the definition and reclassification of
      cribriform lesions in distinct categories and sometimes very different in terms
      of progression, prognosis and treatment. This paper proposes an overview of the
      prostate lesions with cribriform / pseudocribriform architecture, emphasizing the
      morpho-immunohistochemical criteria for positive and differential diagnosis.

PMID- 20809016
TI  - Cellular interactions in prostate cancer genesis and dissemination. Looking
      beyond the obvious.
AB  - Similar to normal organs arising from normal stem cells, cancers can be viewed as
      organs composed of heterogeneous cellular populations arising from cancer cells
      with indefinite proliferation abilities. The continuous malignant progression is
      maintained by the proliferation of cancer stem cells and not the progeny that
      undergo limited proliferation before terminally differentiating. Effective
      therapy must eradicate malignant cells with unlimited clonogenic expansion within
      the primary tumor bulk. Thus, resolving both the specific cell of origin for
      prostate cancer and the interactions between the cells and the surrounding
      microenvironment within the cancer stem cell niche are crucial to appropriately
      define rational targets for therapeutic intervention and cure prostate cancer.

PMID- 20809017
TI  - Recent data about the role of human papillomavirus (HPV) in oncogenesis of head
      and neck cancer.
AB  - Human papillomavirus (HPV) is a small circular DNA-virus and the high-risk types
      16, 18 is implicated in oncogenesis of head and neck cancer--especially
      oropharynx (tonsil and base of tongue), poorly differentiated (the basaloid
      type), locoregional advanced stage, poorly differentiated, at the younger male,
      non-smokers, non-drinkers, sexual behaviors. The prognostic is favorable of human
      papillomavirus tumor status for patients with oropharynx squamous cell carcinoma
      treated with radiotherapy (accelerated fractionation without total dose
      reduction). The impact of HPV-vaccination (ACIP 2007) decreasing the incidence of
      oropharyngeal cancer, but that patients HPV-positive, have good prognostic in
      generally (two-year overall survival: 95%, two-year progression-free survival:
      88%), therefore HPV-vaccination in routine practice it is controversy.

PMID- 20809018
TI  - Human blastocyst culture in IVF: current laboratory applications in reproductive
      medicine practice.
AB  - For fertility patients undergoing in vitro fertilization (IVF), blastocyst
      culture brings a number of potential advantages over laboratory techniques
      leading to traditional cleavage-stage embryo transfer. Because day 2-3 embryos
      normally should transit the oviduct only, their direct exposure to an
      intrauterine microenvironment is physiologically inappropriate. This mismatch is
      obviated by blastocyst transfer. Moreover, the nutritional milieu inside the
      fallopian tube is not the same as within the endometrial compartment, a feature
      possibly antagonistic to implantation when a day 2-3 embryo is placed directly
      within the uterus. Delaying transfer to day 5-6 may also improve reproductive
      outcome by reducing risk of embryo expulsion, given increased myometrial
      pulsatility measured at day 2-3. However, rigid reliance on a blastocyst culture
      approach will more often result in treatment cancellation due to embryo loss (no
      transfer), or having fewer embryos for cryopreservation. The development of
      sequential media to support embryos in extended in vitro culture was a
      significant laboratory refinement, since it enabled direct observation of embryos
      to improve transfer selection bias. This approach, in tandem with blastocyst
      cryopreservation, leads to fewer embryos being transferred and reducing multiple
      gestation rate. This review discusses key features of human blastocyst culture
      and its application in clinical reproductive medicine practice.

PMID- 20809019
TI  - Intraductal papillary mucinous tumors of the pancreas.
AB  - Intraductal papillary mucinous tumors (IPMTs) are benign and malignant lesions
      that arise from the epithelial lining of main pancreatic duct and/or branch
      pancreatic ducts, with excessive mucin production (especially
      hyperplastic/adenomatous variety). Based on the degree of cytoarchitectural
      atypia on microscopic examination, IPMTs are classified as benign, borderline,
      carcinoma in situ and invasive tumors. Imaging examinations are very important to
      establish the diagnosis. Two or more tests are usually required. Transabdominal
      ultrasound, endoscopic ultrasound, computed tomography, magnetic resonance
      cholangiopancreatography and endoscopic retrograde cholangio-pancreatography have
      been used for the diagnosis of IPMTs. The correct diagnosis, achieved until
      recently only with endoscopic retrograde cholangiopancreatography, can be
      currently obtained with non-invasive imaging modalities, particularly computed
      tomography and magnetic resonance imaging. Confirmation of the diagnosis
      requires, however, endoscopic-ultrasound fine-needle aspiration biopsy, followed
      by cytological or microhistological exams. The natural evolution of IPMTs is
      still not clear and the management is consequently still evolving.

PMID- 20809020
TI  - Electron microscopy analysis of skin biopsies in CADASIL disease.
AB  - Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and
      Leukoencephalopathy (CADASIL) is an inherited vascular disorder, non-amyloid and
      non-atherosclerotic, affecting predominantly the central nervous system. We
      examined samples of skin biopsies from six patients (men, 43-52-year-old),
      admitted for treatment in the Neurology Clinic regarding the presence of partial
      motor impairment on upper and lower right limbs, facial asymmetry and phrasing
      impairment (three of the patients); These three patients had family history
      remarkable for early-onset strokes: mother and two brothers deceased by early
      strokes (40-50-year-old). Skin biopsy samples were fixed in glutaraldehyde and
      post-fixed in osmium tetroxyde. After dehydration, tissue samples were embedded
      in Epon. Ultrathin sections were mounted on copper grids and stained with uranyl
      acetate and lead citrate as usual and examined with a transmission electron
      microscope Phillips CM100. In all cases ultrastructural study showed granular
      osmiophilic material (GOM) in extracellular locations, between degenerating
      smooth muscle cells in dermal arteries or in their indentations. Deposits of GOM
      varied in size and electron density. Degeneration and loss of smooth muscle cells
      (SMCs) leads to abnormal enlargement of the space between these cells
      Ultrastructural analysis in three cases showed chromatin condensation and
      peripheral aggregation of nuclear material suggesting cells entry to apoptosis.
      These aspects and the marked destruction of the vascular wall were correlated
      with MRI findings and the severity of clinical manifestations at these patients.
      Our study showed that findings of GOM deposits, degeneration and loss of SMCs
      (probably by apoptosis), cell adhesion elements disturbance are characteristic
      for CADASIL disease and sufficient for diagnose of certainty. Moreover, electron
      microscopy analysis of skin biopsies is a useful tool for a differential
      diagnosis and can be considered as first choice method.

PMID- 20809021
TI  - Immunohistochemical study of p53 and Ki67 in a group of patients with mammary
      carcinoma.
AB  - The study was done over a period of 10 years, 1996-2005 and it included 562
      mammary cancer patients. Of the 562 cases, 100 cases of invasive mammary
      carcinoma included in this study were investigated from an immunohistochemical
      point of view. The p53 overexpression was more frequently seen in patients under
      50 (23 cases, that is 54.76%), compared to those over 50 years old (19 cases,
      that is 45.24%). The positive p53 tumors were more often over 2 cm big. The
      invasive ductal carcinomas were p53-positive in 40 cases (44.44%) of all invasive
      ductal carcinoma cases, and the invasive lobular carcinomas were only positive in
      two cases (20%) of all mammary invasive lobular carcinoma cases. Most cases that
      had the overexpression of the p53-protein (30 cases that is 71.43%) had a high
      histological degree (G3), and only 12 cases (28.57%) had a low histological
      degree (G1 and G2). The overexpression of the p53-protein was present in all
      cases that had a heterogeneous phenotype (with one of the hormonal receptors
      being negative), in over half of the cases that had both hormonal receptors
      negative (59.37% of ER-/PR- phenotype cases) and in only 21.05% of cases that had
      ER+/PR+ phenotype. The association of the p53 overexpression (p53 over 10%), with
      the HER2 (2+ or 3+ score) overexpression was seen in seven patients of the 100
      invasive mammary carcinoma cases included in this study. Consequently, 16.66% of
      p53 positive cases had associated positivity for HER2. Most cases that were p53
      positive had an increased proliferation activity, as determined with Ki67. The
      Ki67 immunostaining analysis has made it clear that this marker has positivity
      presence in all cases. The vast majority of cases had a nuclear marking to Ki67,
      but two cases (2% of cases) had a cytoplasmatic / membrane staining.

PMID- 20809022
TI  - The utility of histopathologic examination in appreciation of mandibular
      osteoporotic status.
AB  - The study was performed on 14 female patients aged between 54 and 83 years,
      presented for insertion of mandibular implants and diagnosed with systemic
      osteoporosis on DXA. Radiological examination showed no striking maxillar bone
      rarefactions or changes in the mandibular cortex form that allows the diagnosis
      of osteoporosis at the jaw. To obtain informations on the health status of
      mandibular bone in these patients, we considered it appropriate to do
      histopathological investigations on fragments of bone harvested from implant
      insertion area. To this end, fragments of bone harvested when performing the new
      alveolus were fixed in Stieve mixture, decalcified with trichloroacetic acid and
      included in paraffin. Five-micrometer thick sections were stained with Goldner's
      Trichrome method and examined microscopically. Histopathology revealed changes of
      different intensity in the organic and vascular components of the mandibular
      bone, in all patients studied, with differences from case to case. Thus,
      confirming that patients with systemic osteoporosis diagnosed by DXA at the
      femoral neck and/or the vertebrae have histological changes in the mandibular
      bone, but the extent of damage is different. Providing detailed information about
      organic component and bone vascularization, crucial components in the early
      stages of osseointegration, histopathology is more useful for assessing
      mandibular osteoporotic status, compared with methods of investigation that aim
      only the mineral component, mineralization being the final stage of
      osseointegration. Highlighting mandibular osteoporotic early lesions by
      histopathological examination allows a patient-specific therapeutic approach and
      could be an accurate method of assessment for required osseointegration period,
      depending on the degree of impairment.

PMID- 20809023
TI  - The study of p53 and CA19-9 prognostic molecular markers in colorectal
      carcinomas.
AB  - Immunohistochemistry represents a relatively new identification technique of
      cellular and tissular antigens due to an antigen-antibody binding interactions,
      applied more and more in the pathology laboratories for positive and differential
      diagnosis of premalignant and malignant lesions and also for evolutive prognosis
      of tumoral formations. Immunohistochemistry coloration is based on the antigen
      antibody affinity, the antibody binding situs being identified either by antibody
      coloration direct methods or by using an indirect method where the marking is
      supplied by antibodies called secondary or even tertiary. The present study is
      based on the immunohistochemical investigation of some molecular markers with a
      prognosis value in colorectal cancers (CCR), like the antibody p53 immune
      expression and of some factors supposed to have prognosis value, such as CA19-9
      (carcinoembryonic antigen, carbohydrate antigen or Lewis antigen). In the last
      decade, the studies have tried to define the prognosis of the molecular markers
      that allow the identification of the patients with recurrent risk after surgical
      treatment and who can benefit from chemotherapy in an efficient way. The purpose
      of the study on immunohistochemical markers is to aim towards the treatment based
      on molecular phenotypes of colorectal tumors. In 2000, according to the Consensus
      Conference of the Colorectal Working Group of the American Joint Committee on
      Cancer Prognostic Factors (AJC), there were established four categories of
      prognosis factors in colorectal cancers based on the practical importance and the
      number of studies referring to them. The present study is centered on the
      prognosis factors from the second B category (p53 oncoprotein expression) and the
      fourth category (CA19-9 immunomarker expression).

PMID- 20809024
TI  - Vascular and nerve lesions of the diabetic foot--a morphological study.
AB  - The microcirculation in neuropathic diabetic feet is the subject of the same
      changes found in other end organs of the diabetic patients. In diabetic
      neuropathy, abnormal neurogenic regulation of the hemodynamics in the small
      vessels may contribute to the development of microangiopathy, which is manifested
      as increased basement thickening. MATERIAL AND METHODS: The study has been made
      on a group of 25 patients: nine with diabetes mellitus type 1 and 16 patients
      with diabetes mellitus type 2. All patients were affected by peripheral diabetic
      neuropathy and showed various degrees of lesions on the foot level. All cases
      required amputations done at the lower extremity of the limbs. Tissue fragments
      were processed for the standard histopathological exam, using Hemalaun-Eosin,
      trichromic Szekely and van Gieson staining. RESULTS: The histopathological
      examination revealed on the skin level--ulcerations covering large areas, while
      entire sections showed hyperacanthosis. At the dermis level, the microscopic
      panel was dominated by the presence of the inflammatory infiltrate. The absence
      or the degeneration of the sweat glands, the presence of venous stasis and
      perivascular bleedings completed the morphological panel of the dermis. On the
      microcirculation level, the endothelial cells have a flat smooth inflated aspect.
      In the case of the large arterioles and arteries of muscular type, we observed
      the presence of the fibrous tissue on the level of media, calcium deposits on
      intima, mediocalcinosis. CONCLUSIONS: The identification of vascular and nervous
      morphological structures in the complicated diabetic foot allows the extension of
      the knowledge related to the pathological background of this condition. The
      vascular lesions, which appeared on the microcirculation level, are consequently
      involving arterioles and arteries of muscular type and are being accompanied by
      nervous lesions shown through morphological changes of the peripheral nerves. The
      overall morphological contest of the complicated diabetic foot involves lesions
      of the epidermis, dermis, and muscles.

PMID- 20809025
TI  - The three-dimensional modeling of the complex virtual human elbow joint.
AB  - The paper presents the algorithm to obtain a 3D virtual human elbow joint using
      CT images. For that purpose, we used CAD parametric software, which allows
      defining models with a high level of difficulty including complex 3D shapes. The
      virtual biomechanical system of the human elbow containing bones, ligaments and
      muscles is studied using the finite elements method and will be prepared for
      kinematical and dynamical simulations. The 3D virtual model will be useful for
      future studies concerning prosthesis optimization, improving the performances of
      endo-prosthetic and exo-prosthetic devices, different implants and prosthetic
      systems for normal and pathological situations, structures which are acted upon
      by SMA artificial muscles or which contain SMA elements.

PMID- 20809026
TI  - Immunocytochemical expression of p16INK4a and HPV L1 capsid proteins as
      predictive markers of the cervical lesions progression risk.
AB  - Genital HPV infections are extremely common but most of them are spontaneously
      cleared by the host immune response. The main problem is how to identify the HPV
      HR positive patients who are at risk of progressive disease. AIM: The purpose of
      this study was to investigate the uterine cervix lesions concerning the HPV
      status appreciated through the immunocytochemical expression of the L1 HPV and
      p16INK4a proteins. MATERIAL AND METHODS: 76 women who tested positive for HPV
      were selected from a cohort of 374 patients. In this study were detected the
      immunochemical expression of HPV L1 capsid protein and p16INK4a in LBC samples.
      RESULTS: The p16INK4a positive rate was expressed in 56.57% of all the cases. The
      percentage grew from 0% in NILM cases to 100% in SCCs cases (p-value <0.00001).
      The HPV L1 capsid protein positive was expressed in 12.50% of NILM cases, 33.33%
      of ASC-US, 50% of LSIL, 18.51% of HSILs cases, but 0% in the SCC group (p-value =
      0.01). The L1-/p16+ pattern was found in 21.87% of LSIL, 81.48% of HSIL, and 100%
      of SCC cases (p-value <0.00001). The association of these two markers (L1 and
      p16INK4a) raises the accuracy of the diagnostic from 64% for HPV L1 capsid
      protein and respectively 87% for p16INK4a to 91% when they are associated.
      CONCLUSIONS: The combination of L1 capsid protein and p16 appears to be useful
      for an early diagnosis and may be able to identify the patients with risk of
      lesion progression.

PMID- 20809027
TI  - Assessment of sagittal and vertical skeletal patterns in Romanian patients with
      obstructive sleep apnea.
AB  - OBJECTIVE: To establish the sagittal and vertical skeletal pattern of the
      Romanian patients with obstructive sleep apnea (OSA). PATIENTS AND METHODS:
      Lateral cephalograms of forty patients, divided in two groups, group I--twenty
      patients with OSA (15 males and five females) and aged between 34-76 years and
      group II (control group)--twenty patients with class II malocclusion (eight males
      and 12 females), aged between 22-40 years, were analyzed for linear and angular
      skeletal parameters. RESULTS: For group I--most often, the mandible was in
      posterior position, the mean value for SNB angle being 76.77 degrees; maxilla
      tended to be retruded, too. The maxillo-mandibular antero-posterior (AP)
      relationship was class II in 90% of the cases. A clockwise rotation of the
      mandible was registered in a vertical plane (mean value SN, ML: 29.82 degrees),
      the facial height ratio being in a normal range of values. There was a medium
      positive correlation between ANB angle and apnea/hypopnea index (AHI), while SNA
      showed a quadratic relationship with AHI. Using t-test, in order to compare the
      sagittal and vertical skeletal pattern of the two groups, it can be stated that
      there is a statistical significant difference for antero-posterior (AP) position
      of the mandible, for the group II mandible retrognathia being more pronounced
      than in group I. CONCLUSIONS: Romanian patients with OSA had a retrognathic
      sagittal pattern with a class II antero-posterior relationship. A statistical
      significant positive correlation between AHI and ANB suggests that the class II
      antero-posterior maxillomandibular relationship can predispose to OSA.

PMID- 20809028
TI  - Steatosis and serum lipid patterns in patients with chronic viral hepatitis:
      differences related to viral etiology.
AB  - Lipid metabolism disorders related to viral etiology are described in chronic
      viral hepatitis, independent of age, gender and liver synthetic function.
      Steatosis is present, especially in chronic hepatitis C but also in chronic
      hepatitis B. Although liver biopsy is the gold standard in determining presence
      of steatosis, its presence can be determined by ultrasonographic examination as
      an initial screening test. Our aim in this study was to evaluate the presence of
      steatosis in chronic hepatitis B and C, to determine its frequency in both
      hepatitis type, and to explore possible relationships between presence of
      steatosis, lipid metabolism disorders and viral etiology. Our study lot included
      66 patients, 36 subjects with chronic hepatitis C, and 30 with chronic hepatitis
      B. We only encountered significant levels of steatosis in the chronic hepatitis B
      sub-group. We found the average age, cholesterol, triglyceride, HDL-C, VLDL-C
      levels in the group with steatosis to be significantly higher than those in the
      group without steatosis (p < 0.05). Ultrasound reports of hepatic steatosis were
      particularly associated with histological inflammation, as well as fibrosis;
      however, the sensitivity and specificity of steatosis on ultrasound was poor when
      compared to steatosis on biopsy. Hepatic steatosis was significantly more
      frequent in chronic hepatitis C than in chronic hepatitis B. Severe inflammation
      and advanced fibrosis were more frequently found in HCV-infected patients with
      steatosis than in patients without steatosis.

PMID- 20809029
TI  - Correlations between the gingival crevicular fluid MMP8 levels and gingival
      overgrowth in patients with fixed orthodontic devices.
AB  - Levels of metalloproteinase 8 (MMP8) in gingival crevicular fluid were studied in
      case of treatment with fixed orthodontic appliances. It were found a relationship
      between its levels and stages of the treatment under a good control of the
      bacterial plaque. Gingival overgrowth (GO) during the orthodontic treatment was
      traditionally considered as an inflammatory reaction consecutive of bacterial
      plaque accumulation because of difficult hygiene in those patients. Our study
      starts from the hypothesis that the gingival volume growth during the fixed
      orthodontic treatment appears at the beginning, without any inflammatory signs,
      as a result of the mechanical stress and periodontal remodeling during the
      orthodontic dental movement, the MMP8 acting as an indicator of this situation.
      MATERIAL AND METHODS: Twenty-two patients received a fixed orthodontic treatment.
      Periodontal examination took place one hour before and one hour, four and eight
      hours and weekly after until eight weeks. At each session gingival crevicular
      fluid (GCF) was sampled and the level of MMP8 was determined. At the appearance
      of gingival overgrowth (GO) gingivectomy was performed. RESULTS: In the 13
      patients that did not develop gingival overgrowth, the levels of MMP8 increased
      in the first 4-8 hours after orthodontic appliance and then fall to the initial
      level. In the nine patients with gingival overgrowth, the MMP8 levels in GCF
      continued to rise until the appearance of GO. In cases of GO with inflammation
      the levels of MMP8 were significantly higher than in cases of GO without
      inflammation. The expression of MMP8 in hypertrophied gingiva was more intensive
      in cases of GO with inflammation. CONCLUSIONS: It is possible that the MMP8
      values in GCF to be a marker of the GO onset. MMP8 determination and monitoring
      at shorter time intervals may lead to a better control of the bacterial plaque
      and avoidance of gingival inflammation.

PMID- 20809030
TI  - Radiographic study of carrying angle and morphometry of skeletal elements of
      human elbow.
AB  - Lateral obliquity of the forearm from the arm when the forearm is supinated and
      extended is called carrying angle. In this study carrying angle was measured
      using radiographs of adult individuals and morphometry was done on dry bones
      taking part in formation of human elbow (on lower end of humerus-trochlear angle
      and inclination angle of olecranon fossa, on upper end of ulna-olecranon-coronoid
      angle and length and width of inferior medial trochlear notch). On radiographs,
      the difference between male and female carrying angle and difference between
      carrying angle of right and left limbs (in both sexes together as well as in same
      sex) was statistically not significant. All the morphometric parameters measured
      in this study did not show any significant sexual dimorphism or difference
      between right and left side except the inclination angle of olecranon fossa,
      which was significantly more on right side. Different findings of carrying angle
      as reported by various authors could be due to racial difference or due to
      different methods used to measure carrying angle. Morphometric parameters were
      similar to findings of radiographic method of measuring carrying angle. These
      factors should also be considered in construction of elbow prosthesis as well as
      use of carrying angle in identification of skeletal remains.

PMID- 20809031
TI  - Cytomorphometric analysis of buccal mucosa of tobacco chewers.
AB  - OBJECTIVE: The objective of the present study was to assess the effect of tobacco
      chewing on buccal mucosa by using cytomorphometry. STUDY DESIGN: We compared the
      cellular diameter (CD), nuclear diameter (ND) and the ratio of nuclear diameter
      to cellular diameter (N/C) of buccal mucosa squames of normal subjects (N) with
      buccal mucosa squames of tobacco users without lesion (A), with tobacco-lime
      lesion (B), leukoplakia (C), and oral squamous cell carcinoma (D). The study
      group consisted of 125 patients divided into five groups (N, A, B, C and D)
      between the ages of 21 and 75 years. RESULTS: The mean of the cellular diameter
      (in micrometers) of group N, A, B, C, and D was 72.86+/-5.26, 68.30+/-3.02,
      62.13+/-3.29, 57.75+/-4.66, 54.51+/-4.66 respectively (p<0.01). The mean of the
      nuclear diameter (in micrometers) of group N, A, B, C, and D was 8.70+/-1.30,
      8.98+/-1.08, 9.06+/-0.83, 9.12+/-1.06, and 11.04+/-1.46 respectively (p<0.01).
      The mean of the ratio of nuclear diameter to cellular diameter of group N, A, B,
      C, and D was 0.11+/-2.00, 0.13+/-1.82, 0.14+/-1.35, 0.16+/-3.11, 0.21+/-4.51
      respectively (p<0.01). Univariate analysis of variance (ANOVA) showed a
      significant group effect for cellular diameter, nuclear diameter and ratio of
      nuclear diameter to cellular diameter. Multiple comparison tests by Tukey-HSD
      procedure revealed a significant decrease in the mean cellular diameter, increase
      in the nuclear diameter and ratio of nuclear diameter to cellular diameter.
      CONCLUSIONS: Cytomorphometric changes could be the earliest indicators of
      cellular alterations. There is progressive decrease in cellular diameter,
      increase in nuclear diameter and increase in ratio of nuclear diameter to
      cellular diameter in smears from all tobacco users, as compared to normal
      subjects. This indicates that there could be cause-effect relationship between
      tobacco and quantitative alterations.

PMID- 20809032
TI  - Renal artery variations: embryological basis and surgical correlation.
AB  - Understanding anatomy of the vascular variations of kidney is essential for the
      clinician to perform procedures such as renal transplantation, interventional
      radiological procedures and renal vascular operations more safely and
      efficiently. In order to facilitate the clinical approaches, we studied renal
      arterial pattern in 50 formalin-fixed cadavers, on 100 kidneys. We observed
      prehilar multiple branching patterns in 11 (11.66%) cases, duplication of renal
      artery in eight (8.33%) cases and superior polar artery in seven (6.66%) cases.
      In the present study findings discussed with its clinical correlation.

PMID- 20809033
TI  - Maturation of the neuromuscular junction in masseters of human fetus.
AB  - OBJECTIVES: The aim of the present investigation is to examine if the
      histological maturation of the neuromuscular junction in the masseters of human
      fetuses has already begun by the 12-th week of gestation or not. MATERIAL AND
      METHODS: Twenty-four masseter muscles from 14 human fetuses at gestational age 12
      weeks were divided into two groups. In the first group, muscle sections were
      stained with Bielschowsky and Holzer stains for examination of neurofibrils and
      glial cells respectively. In the second group, rhodamine and fluorescein
      conjugated alpha-bungarotoxin were used to detect nicotinic receptors and anti
      GAD for neuronal terminals. RESULTS: It was observed the presence of one axon for
      each end-plate and glial cells spread over a branched axon. The nicotinic
      receptors clustered in the neuromuscular junction, neuronal terminals and large
      oval nucleus were detected. CONCLUSIONS: These observations suggest that the
      maturation of the neuromuscular junctions of the masseter muscles in the human
      fetuses has already begun at the 12-th week of gestation.

PMID- 20809034
TI  - Urinary bladder diverticulum and its association with malignancy: an anatomical
      study on cadavers.
AB  - Present work was directed to study the prevalence and anatomical basis of
      diverticulum formation and its association with malignancy inside the urinary
      bladder on cadavers. Urinary bladder diverticulum and its complications including
      malignancy has been reported by different authors based on their study on
      radiological findings and endoscopy. Present study was undertaken on cadavers to
      meet the aforementioned objectives. Thirty properly embalmed cadavers (19 males
      and 11 females) of different ages were dissected. Sagittal section of pelvis was
      studied. Urinary bladder was incised to expose the interior and it was examined
      for the presence of diverticulum (including number and location). Detailed
      history of the cause of death of cadavers with diverticulum was studied to
      determine how many of them suffered from urinary bladder diverticular carcinoma.
      23.4% cadavers (31.6% males and 9.1% females) showed presence of urinary bladder
      diverticulum. The location of the diverticulum in all the cadavers was on
      superior and lateral side of the ureteric opening on the posterior surface of the
      urinary bladder. Diverticulum of one male cadaver aged 74 years was complicated
      by malignancy. Our study observed greater prevalence of diverticulum formation as
      compared to previous reports. In the present work, 14.3% diverticulum of the
      urinary bladder showed malignant change, which is more than earlier reports in
      the literature. Urinary bladder diverticulum should neither be neglected nor
      ignored. Appropriate early treatment (including the cause) of the diverticulum
      should be undertaken to avoid complications like malignancy which will finally
      ensure longevity.

PMID- 20809035
TI  - Palmar dermatoglyphics in carcinoma breast of Indian women.
AB  - The present study was planned to assess the relationship of palmar dermatoglyphic
      patterns of hands in women with breast cancer and or at risk for developing
      breast cancer. This study was conducted on 100 histopathologically confirmed
      breast cancer patients in women and their digital dermatoglyphic patterns were
      studied to assess their association with the type and onset of breast cancer.
      Simultaneously 100 age-matched controls were also selected with no self or
      familial history of a diagnosed breast cancer and the observations were recorded.
      The differences of qualitative (dermatoglyphic patterns) data were tested for
      their significance using the chi-square test, and Student's t-test was used for
      quantitative (ridge counts and pattern intensity index) data analysis. The
      results of the study indicated statistically significant changes in finger ridge
      count and fingertip pattern in cases of carcinoma breast as compared to the
      control group. Palmar dermatoglyphics is simple, inexpensive, anatomical and non
      invasive and may be used as a reliable indicator for screening of high-risk
      population in developing country like India, for early detection and early
      therapy, thus reducing the morbidity and mortality in cases of carcinoma breast.

PMID- 20809036
TI  - An anatomical and clinical insight on brachialis with emphasis on portal's
      muscle.
AB  - There have been conflicting descriptions regarding the anatomy of portal's muscle
      in the literature. The purpose of the present study seeks to clarify the
      presence, morphology, and potential function of this muscle in order to refine
      surgical techniques around the elbow. Forty-eight formalin fixed upper
      extremities were dissected and observed for attachments of brachialis
      meticulously and particularly over the anterior elbow joint capsule with special
      emphasis to the anatomical relation of the deeper fibers to the joint. It was
      found that there were varying patterns of muscular attachments over the anterior
      joint capsule with majority of the fibers of brachialis simply passing
      superficial to the joint capsule. The highest concentration of fibers was noted
      on the inferior part of the joint capsule, which was attached via connective
      tissue. These fibers were the deepest fibers of brachialis muscle that had no
      affect on the joint capsule following tension. Knowledge of this muscle may help
      the surgeons who operate in the elbow region to be tension free in preserving
      such fibers of clinically less importance.

PMID- 20809037
TI  - Prostatic blue nevus.
AB  - We report the case of a 69-year-old patient with no significant personal
      urological history. The clinical and ultrasound examination revealed a prostatic
      gland with increased volume and homogenous appearance. After transurethral
      resection, multiples gray-brown-blackish prostatic chips were obtained, which
      could be confused with a malignant melanoma. The histological routine examination
      in conjunction with the histochemical (Fontana-Masson) and immunohistochemical
      (S100, HMB45) reactions established the diagnosis of prostatic blue nevus. The
      presence of melanin in prostatic tissue is an unusual aspect, being encountered
      three distinct lesions: blue nevus, melanosis and malignant melanoma. Recognition
      and correct classification of each of these three entities is fundamental,
      concerning the clinical and prognosis implications.

PMID- 20809038
TI  - Plaque-type morphea in children.
AB  - We present the case of a girl, aged 8-year-old, with a history of acrocyanosis
      and repeated respiratory infections with beta-hemolytic streptococcus, which was
      consulted for the presence of skin lesions in the right buttock area. Clinical
      examination showed, in the right buttock region, an oval plaque with a diameter
      about 12 cm, hard, well defined, with irregular outline. The biopsy was performed
      and it revealed typical aspects of plaque-type morphea. The epidermis was mostly
      atrophic, with areas of ridge reduction; an important proliferation of collagen
      fibers within superficial and deep dermis and an abundant lymphocytic
      inflammatory infiltrate throughout the dermal thickness reaching hypodermic level
      and infiltrating it. General treatment consisted of antibiotics; vitamin E; local
      treatment with topical cortisone; analogues of vitamin D3 to which we associated
      topical adjuvants with repairing and healing role applied to the biopsied area.
      Evolution was favorable after three months of treatment, with obvious improvement
      of skin lesions; skin became more elastic and the purple red contour ring
      disappeared.

PMID- 20809039
TI  - Treatment of a mandibular canine abutment with two canals.
AB  - Human mandibular canines do not present an internal anatomy as simple as could be
      expected; there are such canines with a single root and two canals, two roots or
      fused roots. The existence of mandibular canines with more than one root canal is
      a fact that clinicians ought to keep in mind, in order to avoid failure during
      endodontic treatment. In spite of the low incidence of lower canines with one
      root and two canals, this possibility cannot be forgotten, inasmuch as the
      presence of a second canal in these teeth leads to difficulties in endodontic
      treatment. The precise knowledge of the dental endocanalicular system's anatomy
      is essential in the success of the root canal therapy, because the failure to
      detect the accessories canals and the incomplete radicular obturation leads to
      the infection of the periapical space, which will ultimately result in the loss
      of the tooth. The long-term success of the prosthodontic treatment depends
      directly on the quality of the endodontic treatment realized on the abutment
      teeth. The mandibular canine is very important as abutment for any type of
      prosthetic restoration. This article presents a clinical case of a canine tooth
      which displays a radicular morphology with two canals, which leads us to conclude
      that such anatomical variations on human teeth can also occur in our country as
      much as described in the international literature and cannot be overlooked when
      treating the teeth.

PMID- 20809040
TI  - Coexisting of aortic arch variation of the left common carotid artery arising
      from brachiocephalic trunk and absence of the main branches of right subclavian
      artery: a review of the literature.
AB  - The variations in the aortic arch and its branches are of surgical interest. Many
      anomalies of the aortic arch and great vessels are uncovered as serendipitous
      findings on imaging studies, in the anatomy laboratory, or at surgery. A 56-year
      old woman had an arch angiogram as part of an evaluation for cardiovascular
      disease. A two-vessel left aortic arch was identified consisting of the
      brachiocephalic trunk and left subclavian artery. In this study, we present a
      case of the left common carotid (LCC) artery arising from the brachiocephalic
      trunk (BT) and absence of the main branches of right subclavian artery in her
      angiographic imaging findings. There is no previous report about LCC artery
      arising from BT and absence of the main branches of right subclavian artery in
      the same person.

PMID- 20809041
TI  - Invasive thymoma.
AB  - Thymomas are rare tumors of the thymic epithelium with a broad spectrum of
      morphological and clinical features. Despite a benign histological appearance, it
      can invade nearby structures or metastasize. The majority of patients are
      asymptomatic, but some may present with paraneoplastic syndromes such as
      myasthenia gravis, red cell aplasia, or hypogammaglobulinemia. Various staging
      systems of thymomas have been defined based on the degree of invasiveness.
      According to the WHO Classification, there are six histologic types of thymic
      epithelial tumors. The most important prognostic factor is the stage according to
      Masaoka's system. We report a case of invasive thymoma diagnosed incidentally in
      a patient with cardiovascular risk factors referred to the cardiologist with
      suspected thoracic aorta aneurism.

PMID- 20809042
TI  - Supratentorial pilocytic astrocytoma in children.
AB  - Brain tumors hold second place in tumoral pediatric pathology and have a complex
      etiopathogeny. The authors describe the case of a child aged 2 years and 4 months
      with increased intracranial pressure, symptomatology accompanied by rapid
      deterioration of general condition. Head CT imaging examination showed intra
      nevraxial replacement space process, supratentorial. Histopathological
      examination revealed the typical grade I pilocytic astrocytoma. Time of diagnosis
      and surgical intervention is essential for further evolution and prognosis.

PMID- 20809043
TI  - Oral manifestations in Apert syndrome: case presentation and a brief review of
      the literature.
AB  - BACKGROUND: The present paper describes the oral manifestations in a 16-year-old
      boy previously diagnosed with Apert syndrome. PATIENT AND METHODS: The extraoral
      and intraoral pathological findings were recorded. The following intraoral
      parameters were recorded: plaque and calculus deposits, dental caries,
      periodontal status, malpositions, and occlusion. For the upper anterior teeth,
      dental shade was recorded, using a dental spectrophotometer. The corresponding
      diagnostics were established. A treatment plan was established and discussed with
      the child's parents. RESULTS: The dysmorphic characters were obvious, including
      acrocephaly, prominent forehead, hypoplastic midface, hypertelorism, short nose.
      The intraoral features revealed a bifid uvula and Byzantine-arch palate
      associated with lateral swellings of the palatine processes, one on either side
      of the middle miming a pseudocleft in the midline. Heavy dental plaque, dental
      calculus, congestion and swelling of the gingiva and periodontal pseudopockets
      associated with anterior teeth were recorded. Dental caries on anterior and
      posterior teeth were present. Severe maxillary dental crowding associated with
      the rotation of central incisors and the palatal position of second bicuspids and
      the malposition of the mandibular anterior teeth were observed. No intrinsic
      discoloration of the dental structure was recorded. Severe anterior and posterior
      open bite and crossbite were observed. Other signs were represented by syndactyly
      involving partial fusion of the fingers and toes. Also, mild mental deficiency
      was recorded. CONCLUSIONS: The information and the strong motivation of the
      parents regarding the necessity of the treatment and the extensive use of home
      prevention methods are essential to control oral conditions in these patients.

PMID- 20809044
TI  - Multiple variations in the branching pattern of the abdominal aorta.
AB  - We report on a unique clinically and surgically significant case of multiple
      abdominal aorta variations. Specifically, the left inferior phrenic, left gastric
      and splenic artery arose in common from the left aspect of the aorta constituting
      a common phrenogastrosplenic trunk, while the common hepatic artery originated
      separately from the midline of the anterior aspect of the aorta just inferiorly
      to the trunk. An accessory right hepatic artery arises from the right-anterior
      aspect of the abdominal aorta adjacent to superior mesenteric artery origin. On
      the left side, two renal arteries were observed. Moreover, the left gonadal
      artery exhibited a high origin, arising inferiorly to the upper left renal
      artery. We discuss about the embryological development of abdominal aorta
      arterial abnormalities and we attempt to sort the noticed variations according to
      existing classification in the literature. It is highlighted that the thorough
      knowledge of these arterial variations is important for the success of upper
      abdomen surgical operations such as liver and kidney transplantation, kidney
      preservation, abdominal aorta related vascular surgery, treatment of
      hepatocellular carcinoma by transcatheter arterial chemoembolizations as well as
      imaging interpretation of the region. Preoperative selective angiography or other
      abdominal aorta imaging studies are helpful for arterial variation demonstration
      and a precious tool for appropriate surgery planning.

PMID- 20809045
TI  - Ectopic kidney with malrotation and bilateral multiple arteries diagnosed using
      CT angiography.
AB  - Right renal ectopia with malrotation was seen on a CT angiography in a 64-year
      old male patient. Bilateral triple renal arteries were also revealed: one main
      (superior) renal artery and two accessory arteries (middle and inferior), all
      originating in the abdominal aorta. The renal arteries are disposed
      symmetrically. The main arteries and the accessory ones are of equal caliber.
      Simple renal ectopia is a congenital malformation with an incidence of 1-2 cases
      in 1000 births; of these, only one of 10 cases is diagnosed. Like our case, many
      such cases are diagnosed by accident, during investigations of causes that have
      no connection with renal ectopia. Variations in kidney position and renal
      vascular variants are very important clinically, for both the complications they
      may generate and the technical difficulties of certain surgical interventions. CT
      angiography is a minimally invasive method that allows the identification of
      malformations or anatomic variations, providing accurate information on position,
      size and anatomic ratios, which are very useful in diagnosing and treating
      various affections.

PMID- 20809046
TI  - Anomalous branching pattern of the external carotid artery: a case report.
AB  - Variations in the branching pattern of the external carotid artery (ECA) are well
      known and documented. The variation in the present case was compared with those
      reported before. An anomalous unilateral variation in the branching pattern of
      the left ECA was observed in a male embalmed cadaver. In this case, the ECA gives
      a direct branch directly to the submandibular salivary gland, a thyrolingual
      trunk, an auriculo-occipital trunk and a facial artery with an unusual course.
      The embryogenesis of such a combination of anomalies is not clear, but the
      anatomic consequences may have important clinical implications. Anatomical
      knowledge of the origin, course, and branching pattern of the external carotid
      artery will be useful to surgeons when ligating the vessels during head and neck
      surgeries.

PMID- 20809047
TI  - A longitudinal, integrated, clinical, histological and mRNA profiling study of
      resistance exercise in myositis.
AB  - Polymyositis and dermatomyositis are orphan, chronic skeletal muscle disorders
      characterized by weakness, infiltrations by mononuclear inflammatory cells, and
      fibrosis. Until recently, patients were advised to refrain from physical activity
      because of fears of exacerbation of muscle inflammation. However, recent studies
      have shown that moderate exercise training in combination with immunosuppressive
      drugs can improve muscle performance. Despite the positive effects of exercise
      training, the molecular mechanisms underlying the exercise-associated clinical
      improvements remain poorly understood. The present study was designed to define,
      at the molecular level, the effects of resistance exercise training on muscle
      performance and disease progression in myositis patients. We evaluated changes in
      muscle strength, histology and genome-wide mRNA profiles to determine the
      beneficial effects of exercise and determine the possible molecular changes
      associated with improved muscle performance. A total of 8 myositis patients
      underwent a 7-wk resistance exercise training program that resulted in improved
      muscle strength and increased maximal oxygen uptake (VO(2max)). Training also
      resulted in marked reductions in gene expression, reflecting reductions in
      proinflammatory and profibrotic gene networks, changes that were also accompanied
      by a reduction in tissue fibrosis. Consistent with the exercise-associated
      increase in VO(2max), a subset of transcripts was associated with a shift toward
      oxidative metabolism. The changes in gene expression reported in the present
      study are in agreement with the performance improvements induced by exercise and
      suggest that resistance exercise training can induce a reduction in inflammation
      and fibrosis in skeletal muscle.

PMID- 20809048
TI  - Prevention of inflammation-associated preterm birth by knockdown of the
      endothelin-1-matrix metalloproteinase-1 pathway.
AB  - Premature delivery occurs in 12% of all births, accounts for nearly half of
      neonatal morbidity and is increasing in frequency. Current therapeutic approaches
      to preterm delivery are ineffective and present serious risks to both the mother
      and fetus. Although there are multiple factors that contribute to the etiology of
      preterm birth, the single most common cause is infection. Recently, using cDNA
      microarray analysis of human placental tissue, we demonstrated that human
      placental matrix metalloproteinase-1 (MMP-1) is upregulated during labor. In a
      separate line of investigation, we have shown that blockade of endothelin-1 (ET
      1) action through the use of an endothelin-converting enzyme-1 (ECE-1) inhibitor,
      an established commercially available endothelin receptor antagonist or a novel
      quinolone-derived endothelin receptor antagonist synthesized by our group also
      prevents preterm labor and delivery in a mouse model. We have now shown that
      induction of preterm labor with lipopolysaccharide in our mouse model is
      associated with increased levels of MMP-1. Furthermore, we showed that silencing
      the ECE-1/ET-1 pathway by using ECE-1 RNA interference prevents both the onset of
      preterm labor and upregulation of MMP-1. The data indicate that ET-1 and MMP-1
      act in the same molecular pathway in preterm labor.

PMID- 20809051
TI  - Use of the International Classification of Functioning, Disability and Health to
      describe patient-reported disability: a comparison of Guillain Barre syndrome
      with multiple sclerosis in a community cohort.
AB  - OBJECTIVE: To use the International Classification of Functioning, Disability and
      Health (ICF) to describe and compare patient-reported disability in Guillain
      Barre syndrome survivors and persons with multiple sclerosis, and to identify
      relevant environmental factors. METHODS: Cross-sectional survey of 77 survivors
      of Guillain-Barre syndrome in the community. Their Guillain-Barre syndrome
      related problems were linked with ICF categories (second level) using an open
      ended questionnaire, consensus between health professionals and the "linking
      rules", and compared with similar data collected previously for 101 persons with
      multiple sclerosis. RESULTS: Guillain-Barre syndrome survivors were male (59%)
      and older than persons with multiple sclerosis (mean age 55 vs 49 years). Of 170
      ICF categories, 113 were relevant for Guillain-Barre syndrome survivors (mean
      number 30 vs 18 for persons with multiple sclerosis). The linked categories for
      Guillain-Barre syndrome included: body function 27 (56%) compared with 48 (42%)
      for persons with multiple sclerosis; body structure 11 (68%) vs 16 (34%);
      activities and participation 48 (70%) and 68 (58%); and for environmental factors
      27 (71%) compared with 38 (51%) for persons with multiple sclerosis. The main
      areas linked in the activities and participation domain were mobility, major life
      areas and interpersonal relationships; and environmental factors included support
      and relationships, attitudes and products and technology. CONCLUSION: This is the
      first study to use ICF in Guillain-Barre syndrome survivors and towards
      development of the ICF Core Set for Guillain-Barre syndrome from a broader
      international perspective.

PMID- 20809049
TI  - Phosphorylation of extracellular signal-regulated kinase (ERK)-1/2 Is associated
      with the downregulation of peroxisome proliferator-activated receptor (PPAR)
      gamma during polymicrobial sepsis.
AB  - Peroxisome proliferator-activated receptor (PPAR)-gamma is a ligand-activated
      transcription factor and regulates inflammation. Posttranslational modifications
      regulate the function of PPARgamma, potentially affecting inflammation. PPARgamma
      contains a mitogen-activated protein kinase (MAPK) site, and phosphorylation by
      extracellular signal-regulated kinase (ERK)-1/2 leads to inhibition of PPARgamma.
      This study investigated the kinetics of PPARgamma expression and activation in
      parenchymal and immune cells in sepsis using the MAPK/ERK kinase (MEK)-1
      inhibitor, an upstream kinase of ERK1/2. Adult male Sprague Dawley rats were
      subjected to polymicrobial sepsis by cecal ligation and puncture. Rats received
      intraperitoneal injection of vehicle or the MEK1 inhibitor PD98059 (5 mg/kg) 30
      min before cecal ligation and puncture. Rats were euthanized at 0, 1, 3, 6 and 18
      h after cecal ligation and puncture. Control animals used were animals at time 0
      h. Lung, plasma and peripheral blood mononuclear cells (PBMCs) were collected for
      biochemical assays. In vehicle-treated rats, polymicrobial sepsis resulted in
      significant lung injury. In the lung and PBMCs, nuclear levels of PPARgamma were
      decreased and associated with an increase in phosphorylated PPARgamma and
      phosphorylated ERK1/2 levels. Treatment with the MEK1 inhibitor increased the
      antiinflammatory plasma adipokine adiponectin, restored PPARgamma expression in
      PBMCs and lung, and decreased lung injury. The inflammatory effects of sepsis
      cause changes in PPARgamma expression and activation, in part, because of
      phosphorylation of PPARgamma by ERK1/2. This phosphorylation can be reversed by
      ERK1/2 inhibition, thereby improving lung injury.

PMID- 20809052
TI  - Validation of the London Chest Activity of Daily Living scale in patients with
      heart failure.
AB  - BACKGROUND: The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is a
      well-validated, commonly-used tool to assess quality of life in patients with
      heart failure. However, it lacks specific information concerning breathlessness
      during daily activities. OBJECTIVE: To determine the validity of the London Chest
      Activity of Daily Living (LCADL) scale for use in patients with heart failure.
      METHODS: Forty-seven patients with heart failure (57% males, mean age 50 years
      (standard deviation 9), mean left ventricle ejection fraction 29% (SD 6), New
      York Heart Association (NYHA) functional class I-III) were included. All subjects
      first performed a cardiopulmonary exercise test and then responded to the LCADL
      and the MLHFQ, with guidance from the same investigator. The re-test for the
      LCADL was applied one week later. RESULTS: LCADL was correlated with MLHFQ (r =
      0.88; p < 0.0001). LCADL and MLHFQ were also correlated with exercise capacity (r
      = -0.75 and r = -0.73, respectively; both p < 0.0001). The LCADL was shown to be
      reproducible (ri = 0.98). There was a significant difference (p < 0.05) in the
      LCADL scores between NYHA functional classes I and II, as well as classes I and
      III, but not between classes II and III. CONCLUSION: The LCADL was shown to be a
      valid measurement of dyspnoea during daily activities in patients with heart
      failure. This scale could be an additional useful tool for the assessment of
      patients' dyspnoea during activities of daily living.

PMID- 20809053
TI  - Cost of walking, exertional dyspnoea and fatigue in individuals with multiple
      sclerosis not requiring assistive devices.
AB  - OBJECTIVE: To assess the cost of walking in individuals with multiple sclerosis
      and to investigate its relationship with dyspnoea and fatigue. METHODS: In 46
      individuals with multiple sclerosis and in 36 healthy controls, the cost of
      walking was measured during the 6-min walk test. Perceived breathlessness after
      walking was rated on a visual analogue scale and corrected for the distance
      walked. The subjects' perceived effect of fatigue was assessed by means of the
      Modified Fatigue Impact Scale. RESULTS: The cost of walking was significantly
      higher in individuals with multiple sclerosis than in controls; however,
      individuals with multiple sclerosis with normal walking speeds had normal costs
      of walking. The cost of walking was directly related to the degree of disability,
      but not to breathlessness perception and fatigue. Individuals with an Expanded
      Disability Status Scale score greater than 2.5 were highly likely to show an
      increased cost of walking. Breathlessness perception was higher than in controls
      and was related to fatigue. CONCLUSION: Individuals with multiple sclerosis, even
      with mild disability and not requiring any assistive devices, may have an
      increase in cost of walking. This suggests that an aerobic training programme
      should be considered in these patients. Energy expenditure when walking is not a
      determinant of fatigue or exertional dyspnoea in individuals with multiple
      sclerosis and low levels of disability.

PMID- 20809054
TI  - Comparing the validity of five participation instruments in persons with spinal
      conditions.
AB  - OBJECTIVE: To evaluate and compare the construct validity of 5 participation
      instruments developed using the International Classification of Functioning,
      Disability and Health (ICF). METHODS: A total of 545 subjects diagnosed and
      treated for a spinal condition at an acute hospital were followed-up and
      consented to complete a questionnaire. Subjects completed 5 participation
      instruments (Impact on Participation and Autonomy (IPA), Keele Assessment of
      Participation (KAP), Participation Measure-Post Acute Care (PM-PAC),
      Participation Objective Participation Subjective (POPS), World Health
      Organization Disability Assessment Schedule II (WHODAS II)). In addition, each
      subject completed a health status instrument and a quality of life instrument.
      The dimensionality, convergent/discriminant validity and known-group validity of
      the participation instruments were assessed. RESULTS: A confirmatory factor
      analysis of the facture structure for the IPA and PM-PAC demonstrated adequate
      model fit. For convergent/discriminant validity, correlations were generally
      higher among similar domains of the WHODAS II, IPA, KAP and PM-PAC, and as
      expected the lowest correlations were observed with the objective domains of the
      POPS. Most instruments demonstrated known-group validity. CONCLUSION: Differences
      in the construct validity evidence of the POPS compared with the other 4
      instruments were noted. To date, there is no gold standard for measuring
      participation, and clinicians and researchers should consider the type of
      information required prior to selecting an instrument.

PMID- 20809055
TI  - Comparing the reliability of five participation instruments in persons with
      spinal conditions.
AB  - OBJECTIVE: To compare the score distribution and reliability of 5 participation
      instruments developed using the International Classification of Functioning,
      Disability and Health. METHODS: Individuals treated for spinal conditions at an
      acute hospital were followed-up and 545 participated. Subjects completed 5
      participation instruments (Impact on Participation and Autonomy (IPA), Keele
      Assessment of Participation (KAP), Participation Measure-Post Acute Care (PM
      PAC), Participation Objective Participation Subjective (POPS) and World Health
      Organization Disability Assessment Schedule II (WHODAS II)). Test-retest
      reliability was assessed in 139 subjects. The score distribution, internal
      consistency and test-retest reliability were assessed. RESULTS: All the
      instruments demonstrated considerable ceiling effects, except for the POPS.
      Internal consistency (Cronbach's alpha) was > or = 0.70 for all domains. The IPA
      and WHODAS II had the highest test-retest values, with intra-class correlation
      coefficients > or = 0.70. The minimal detectable change as a percentage of the
      absolute scale score range was primarily between 20% and 30%. CONCLUSION: The
      IPA, PM-PAC and WHODAS II have similar measurement properties. The KAP was
      designed for -population-based studies and the POPS includes objective and
      subjective information, which may explain some of the differences observed.
      Researchers and clinicians should select an instrument that will fulfil their
      measurement objectives and future studies should assess minimal important change.

PMID- 20809056
TI  - Feasibility of a new concept for measuring actual functional performance in daily
      life of transfemoral amputees.
AB  - OBJECTIVE: Determining the feasibility of implementing a new concept to
      objectively evaluate actual functional abilities of transfemoral amputees into a
      new measuring tool called "Assessment of Daily Activity Performance in
      Transfemoral amputees" (ADAPT). DESIGN: Study 1: cross-sectional design. Study 2:
      repeated measures design. SUBJECTS: Study 1 comprised two groups of 10
      participants, age range 19-72 years. One group used microprocessor-controlled
      knee joints and the other group used mechanically controlled knee joints. Study 2
      comprised 20 participants, age range 31-68 years. METHODS: Two versions of ADAPT
      were assessed in the separate studies. In study 1 performance times on version 1
      of ADAPT were compared between groups. In study 2 participants completed version
      2 of ADAPT twice with a 1 h rest between trials. The Locomotor Capabilities Index
      was administered. Reliability was determined by calculating correlation
      coefficients and by Bland-Altman analyses. RESULTS: In study 1, ADAPT version 1
      proved to be sensitive in detecting differences in performance between groups. In
      study 2, 75% of all correlation coefficients exceeded 0.90 in version 2 of ADAPT.
      Bland-Altman analyses showed high test-retest agreement. CONCLUSION: It is
      feasible to reliably assess actual functional abilities of transfemoral amputees
      using standardized simulations of daily activities. This ADAPT concept is able to
      differentiate between different functional performance levels.

PMID- 20809057
TI  - Reproducibility of three self-report participation measures: The ICF Measure of
      Participation and Activities Screener, the Participation Scale, and the Utrecht
      Scale for Evaluation of Rehabilitation-Participation.
AB  - OBJECTIVE: To assess the reproducibility of 3 participation measures. DESIGN:
      Repeated administration of a postal questionnaire with a 2-week interval.
      PARTICIPANTS: Outpatients (n = 47) from 2 rehabilitation centres and a university
      hospital in The Netherlands. METHODS: Measures were the ICF Measure of
      Participation and Activities Screener (IMPACT-S), the Participation Scale, and
      the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P). Test
      retest reliability was analysed using Cohen's weighted kappa and the intraclass
      correlation coefficient (ICC). Agreement was expressed as the standard error of
      measurement and the smallest detectable change (SDC), substantiated as the ratio
      between the SDC and the standard deviation (SDC/SD). RESULTS: ICC values of the
      IMPACT-S were 0.54-0.90 for the scale scores, 0.92 and 0.74 for sub-total scores
      Activities and Participation, and 0.88 for the total score. The ICC of the
      Participation Scale was 0.82. The ICC of the USER-P was 0.65 for the Frequency
      scale, 0.85 for the Restrictions scale, and 0.84 for the Satisfaction scale. The
      SDC/SD ratios for all measures were small (0.11-0.28) at the group level, but
      large (0.78-1.91) at the individual level. Most participants found all measures
      relevant and easy to complete. CONCLUSION: All 3 measures showed generally
      satisfying reproducibility and were acceptable to the participants.

PMID- 20809058
TI  - Long-term effects of rTMS on motor recovery in patients after subacute stroke.
AB  - OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has been
      recognized as a promising intervention for treatment of stroke patients. However,
      most previous reports have described the short-term effects of rTMS on motor
      performance. We conducted a sham-controlled trial to evaluate long-term effects
      of high-frequency rTMS on motor recovery in subacute stroke patients. METHODS:
      Twenty-eight patients were randomly divided into two groups, and received either
      real or control rTMS. Both treatments were accompanied by motor practice. A daily
      dose of 1000 pulses of subthreshold 10 Hz rTMS was applied over the primary motor
      cortex of the affected hemisphere for 10 days within one month after onset of
      stroke. Motor function was assessed before and after treatment, and 3 months
      after the stroke. RESULTS: Motor function improved in both groups after
      treatment; however, patients who received real rTMS experienced additional
      improvement in motor function of the affected upper limb. Over 3 months after the
      stroke, the time and type of intervention for the Motoricity Index of the
      affected upper extremity showed significant interaction. CONCLUSION: Positive
      long-term effects on motor recovery could be achieved after 10 daily sessions of
      high-frequency rTMS in conjunction with motor practice during the sub-acute
      period of stroke.

PMID- 20809059
TI  - Evidence of reduced sympatho-adrenal and hypothalamic-pituitary activity during
      static muscular work in patients with fibromyalgia.
AB  - OBJECTIVE: To assess activation of the sympathetic nervous system and the
      hypothalamic-pituitary-adrenocortical axis during static exercise in patients
      with fibromyalgia. PATIENTS AND METHODS: Sixteen patients with fibromyalgia and
      16 healthy controls performed a static knee extension until exhaustion. Plasma
      catecholamines, adrenocorticotropic hormone and cortisol, as well as blood
      pressure and heart rate, were assessed before, during and following contraction.
      Plasma C reactive protein was analysed at baseline. RESULTS: Blood pressure and
      heart rate increased during contraction (p < 0.001) and decreased following
      contraction (p < 0.001) in both groups alike. Compared with baseline, plasma
      catecholamines increased during contraction in both groups (p < 0.001), but
      patients with fibromyalgia had lower levels of plasma adrenaline (p < 0.04) and
      noradrenaline (p < 0.08) at all times. Adrenocorticotropic hormone increased at
      exhaustion in controls (p < 0.001), but not in patients with fibromyalgia, who
      also had lower adrenocorticotropic hormone at exhaustion (p < 0.02) compared with
      controls. There were no group differences, or changes over time in plasma
      cortisol. High sensitivity C reactive protein was higher in patients with
      fibromyalgia compared with controls (p < 0.02). CONCLUSION: Patients with
      fibromyalgia exhibited a hypoactive sympatho-adrenal system as well as a hypo
      reactive hypothalamic-pituitary axis during static exercise.

PMID- 20809060
TI  - Who waits for inpatient rehabilitation services in Canada after neurotrauma? A
      population based-study.
AB  - OBJECTIVE: This study examined characteristics of patients with acquired brain
      injury associated with wait times for inpatient rehabilitation compared with a
      control population of patients with acquired spinal cord injury. METHODS: This
      cross-sectional study was based on 9458 patients captured in the National
      Rehabilitation Reporting System in Canada. RESULTS: Waiting for inpatient
      rehabilitation was found to be associated with language, geographical location,
      informal support, pre-admission living arrangement and payer source. The median
      differences in wait time, however, were at most a few days. Persons already
      receiving care had the longest median wait times. CONCLUSION: The data reflect
      only the perspective of providers, and further research needs to examine days to
      inpatient admission using data from acute care.

PMID- 20809061
TI  - Validation of the comprehensive ICF Core Set for rheumatoid arthritis: the
      perspective of physicians.
AB  - OBJECTIVE: The "Comprehensive ICF Core Set for rheumatoid arthritis" represents
      the typical spectrum of problems in functioning of patients with rheumatoid
      arthritis according to the International Classification of Functioning,
      Disability and Health (ICF). The objective of this study was to validate this ICF
      Core Set from the perspective of physicians. METHODS: Physicians experienced in
      rheumatoid arthritis treatment were asked about the problems they commonly treat
      in patients with rheumatoid arthritis in a 3-round survey using the Delphi
      technique. Responses were linked to the ICF. RESULTS: Seventy-nine physicians in
      41 countries named 512 patients' problems. Two hundred and 27 ICF categories were
      linked to these answers. Twenty-six ICF categories were not represented in the
      Comprehensive ICF Core Set for rheumatoid arthritis and 19 aspects were not
      covered by the ICF. CONCLUSION: The content validity of 3 ICF components was well
      supported. However, several body functions were identified that are not covered
      and need to be investigated further.

PMID- 20809062
TI  - Mode of hand training determines cortical reorganisation: a randomized controlled
      study in healthy adults.
AB  - OBJECTIVE: To evaluate two commonly used forms of hand training with respect to
      influence on dexterity and cortical reorganization. SUBJECTS: Thirty healthy
      volunteers (mean age 24.2 years). METHODS: The subjects were randomized to 25 min
      of shaping exercises or general activity training of the non-dominant hand. The
      dexterity and the cortical motor maps (number of excitable positions) of the
      abductor pollicis brevis muscle were evaluated pre- and post-training by the
      Purdue Peg Board test and transcranial magnetic stimulation, respectively.
      RESULTS: After shaping exercises the dexterity increased significantly (p < or =
      0.005) for both hands, mostly so in the non-dominant hand. The cortical motor map
      of the abductor pollicis brevis muscle shifted forwardly into the pre-motor area
      without expanding. After general activity training, no significant improvements
      in dexterity were found for the non-dominant hand. The cortical motor map of the
      non-dominant abductor pollicis brevis muscle expanded significantly (p = 0.03) in
      the posterior (sensory) direction. CONCLUSION: These results indicate that
      shaping exercises, but not general activity training, increase dexterity of the
      trained non-dominant hand in parallel with a shift of location of active
      transcranial magnetic stimulation positions. Shifts of active cortical areas
      might be important for the interpretation of brain plasticity in common
      behavioural tasks.

PMID- 20809063
TI  - Restoration of walking function in an individual with chronic complete (AIS A)
      spinal cord injury.
AB  - OBJECTIVE: The prognosis for further recovery of motor function 2 years after
      complete spinal cord injury is poor. This case report describes recovery of
      walking function in an a 33-year old man two years post T7 spinal cord injury
      American Spinal Injury Association Impairment Scale A following intensive
      physical therapy and robotic locomotor training. DESIGN: Case report. METHODS:
      The subject engaged in an intensive clinic-based physical therapy program and
      research-based robotic locomotor training study over a 7-month period. Physical
      therapy was initiated 4 months prior to entry into the research study, and
      targeted trunk control, upper extremity strength, and upright mobility. On
      initial entry into the robotic locomotor training study the subject's AIS A
      classification was substantiated. Initial, interim, and follow-up tests of
      sensation, strength, sitting balance, spasticity, and mobility were performed.
      RESULTS: Lower extremity motor scores improved from 0/50 to 4/50, bilateral hip
      flexors increased from grade 0/5 to 2/5, warranting injury re-classification from
      American Spinal Injury Association Impairment Scale A to C. Intensive physical
      therapy combined with robotic locomotor training was associated with restoration
      of short distance walking function with lower extremity braces and a walker.
      CONCLUSION: To our knowledge, this is the first report of an individual with
      chronic spinal cord injury American Spinal Injury Association Impairment Scale A
      improving in over-ground walking ability following intensive physical therapy and
      robotic locomotor training. The presence of a neurophysiologically discomplete
      lesion probably permitted training of operational neural pathways and enabled the
      development of useful voluntary movement.

PMID- 20809065
TI  - Anterior hybrid decompression and segmental fixation for adjacent three-level
      cervical spondylosis.
AB  - OBJECTIVE: To evaluate the outcomes of anterior hybrid decompression and
      segmental fixation for adjacent three-level cervical spondylosis. METHODS: 53
      patients with adjacent three-level cervical spondylosis underwent anterior hybrid
      decompression and segmental fixation. Titanium mesh and PEEK cage were used to
      span the defects due to decompression and anterior locking plate was placed over
      the entire construct. Japanese Orthopedic Association (JOA) scores, segmental and
      C2-C7 angles before and after operation were analyzed. RESULTS: The average
      follow up was 37.3 +/- 7.0 months. Bone fusions were observed in all patients at
      follow-up intervals. JOA scores improved from preoperative 8.1 +/- 2.2 (range 4
      13) to 13.1 +/- 2.3 (range 7-16) at final follow-up (P = 0.000). Meanwhile,
      surgical segmental angle was significantly improved from preoperative 6.9 +/- 8.3
      degrees  (range -10.4 degrees  to 27.6 degrees ) to postoperative 16.3 +/- 7.2
      degrees  (range -2.0 degrees  to 37.6 degrees )(P = 0.000), and C2-C7 angle from
      9.7 +/- 8.6 degrees  (range -9.9 degrees  to 27.4 degrees ) to 17.8 +/- 7.7
      degrees  (range -1.2 degrees  to 34.3 degrees ) (P = 0.000). Postoperative
      complications included C5 palsy, cerebrospinal fluid leakage, hematoma, and
      titanium mesh subsidence. CONCLUSION: Anterior hybrid decompression and segmental
      fixation is a safe and effective procedure for adjacent three-level cervical
      spondylosis.

PMID- 20809066
TI  - Brain iron metabolism and its perturbation in neurological diseases.
AB  - Metal ions are of particular importance in brain function, notably iron. A broad
      overview of iron metabolism and its homeostasis both at the cellular level
      (involving regulation at the level of mRNA translation) and the systemic level
      (involving the peptide 'hormone' hepcidin) is presented. The mechanisms of iron
      transport both across the blood-brain barrier and within the brain are then
      examined. The importance of iron in the developing foetus and in early life is
      underlined. We then review the growing corpus of evidence that many
      neurodegenerative diseases (NDs) are the consequence of dysregulation of brain
      iron homeostasis. This results in the production of reactive oxygen species,
      generating reactive aldehydes, which, together with further oxidative insults,
      causes oxidative modification of proteins, manifested by carbonyl formation.
      These misfolded and damaged proteins overwhelm the ubiquitin/proteasome system,
      accumulating the characteristic inclusion bodies found in many NDs. The
      involvement of iron in Alzheimer's disease and Parkinson's disease is then
      examined, with emphasis on recent data linking in particular interactions between
      iron homeostasis and key disease proteins. We conclude that there is overwhelming
      evidence for a direct involvement of iron in NDs.

PMID- 20809067
TI  - Electroconvulsive therapy resolves cortical inhibition and manneristic omissions
      in a chronic catatonic patient.
AB  - We investigated a patient with severe catatonic schizophrenia (manneristic
      catatonia according to Karl Leonhard) treated with electroconvulsive therapy
      (ECT) after pharmacological approaches did not result in any clinical
      improvement. Before and after nine ECT sessions a double-pulse transcranial
      magnetic stimulation (TMS) paradigm was used to measure intracortical inhibition
      (ICI) which has been shown to be reduced in a significant proportion of patients
      with schizophrenia. Although the patient showed no remission regarding some
      psychomotor aspects after ECT, we found an increase in ICI and a remarkable
      clinical improvement of catatonic omissions which might be due to changes in the
      GABAergic system.

PMID- 20809068
TI  - Risk factors for cerebrovascular and cardiovascular diseases beyond age 75 years.
AB  - Globally, cardiovascular diseases (CVDs) are the number one cause of all
      mortalities. Of these deaths, 7.6 million are due to heart attacks, and 5.7
      millions are due to stroke. The Vienna Transdanube Aging Study (VITA), a
      population-based cohort study, enabled us to evaluate associations between the
      known major risk factors for cerebrovascular and CVDs and their appearance beyond
      age 75 years. Using a single birth cohort, age was excluded as confounding
      factor. In the baseline investigations in the Danube Hospital, 606 individuals
      took part and were examined completely at baseline. After 60 months, 508 patients
      were re-examined. Each participant underwent an indepth investigation with the
      duration of 7 h, including neuropsychological testing, as well as analyses of
      biochemical, clinical chemical and genetic parameters, and magnetic resonance
      imaging (MRI) of the brain. In the present study, only a history of cerebral and
      cardiovascular events at the baseline or smoking was associated significantly
      with the appearance of CVDs. In a multiple model both risk factors-history of
      cerebral and cardiovascular events at the baseline (p = 0.0003, OR 2.36, 95% CI
      1.49-3.76) and smoking (p = 0.0005, OR 1.57, 95% CI 1.22-2.03)-remained
      significant. However, the predictive value of this assessment model was low. The
      rescaled r2 of the model was 0.088. A significant correlation was found only
      between exposure to cigarette smoke or a history of previous CVDs, such as stroke
      or myocardial infarction. Smoking or earlier CVDs greatly increase the risk for
      further cerebral and cardiovascular events in persons after 75 years.

PMID- 20809069
TI  - Anticonvulsant action of 2-chloroadenosine against pentetrazol-induced seizures
      in immature rats is due to activation of A1 adenosine receptors.
AB  - Potentiation of adenosinergic inhibitory modulation is one of possible strategies
      to develop new antiepileptic drugs. Nonspecific receptor agonist 2
      chloroadenosine was tested against pentetrazol-induced convulsions in immature
      (7, 12, 18 and 25 days old) and adult rats. Doses of 1-15 mg/kg i.p. suppressed
      tonic phase of generalized tonic-clonic seizures (GTCS) in the two youngest
      groups, whereas GTCS were abolished in older rats. Minimal clonic seizures in 18
      day and older rats were suppressed by high doses of 2-chloroadenosine. The role
      of A1 and A2A adenosine receptors was studied in 12- and 25-day-old rats. Action
      of an agonist of A1 receptors CCPA is similar to that of 2-chloroadenosine. An
      agonist of A2A receptors CGS 21680 exhibits an anticonvulsant action only in the
      dose-inducing catalepsy; an A2A antagonist ZM 241385 moderately suppressed tonic
      phase of GTCS only in 12-day-old animals. Anticonvulsant action of adenosine
      agonists is due to their effects on A1 receptors.

PMID- 20809070
TI  - Decrease in gait variability while counting backward: a marker of "magnet
      effect"?
AB  - Counting backward (CB) and walking are both rhythmic tasks. An improvement of CB
      performance has been reported while walking, and has been interpreted as a
      "magnet effect" which is the tendency of biological oscillators to attract each
      other. The objective of this study was to compare the coefficient of variation
      (CoV) of stride time (ST) and the number of enumerated figures while single- and
      dual-tasking between older adults who increased and decreased their CoV of ST
      while CB. The number of enumerated figures and the CoV of ST under single-task
      (i.e., CB while sitting or walking alone) and dual-task (i.e., CB while walking)
      were measured among 100 community-dwelling older subjects (mean, 69.8 +/- 0.07
      years). Subjects were separated into two groups according to the dual-task
      related changes in CoV of ST (i.e., either above or below the mean value of CoV
      of ST under single-task). Seventeen participants decreased their CoV of ST while
      CB compared to usual walking (2.6 +/- 1.6% vs. 2.0 +/- 1.3%, P < 0.001), while 83
      increased their CoV of ST (1.7 +/- 0.6% vs 3.4 +/- 2.3%, P < 0.001). The subjects
      who decreased their CoV of ST had a tendency to enumerate more figures while
      walking compared to sitting (20.9 +/- 6.3 vs 19.4 +/- 4.7, P = 0.046) unlike
      those who increased their CoV of ST (20.3 +/- 5.0 vs 21.8 +/- 6.0 while sitting,
      P = 0.001). We found that most of subjects had worse gait and CB performance
      while dual-tasking. Conversely, a limited number of subjects improved
      significantly their gait performance and simultaneously had a tendency to improve
      their CB performance while walking compared to sitting. This behavior was
      observed only among subjects with the highest gait variability and could be
      interpreted as an implicit strategy based on the "magnet effect".

PMID- 20809071
TI  - Choroid plexus tumors in children less than 36 months: the Canadian Pediatric
      Brain Tumor Consortium (CPBTC) experience.
AB  - BACKGROUND: Choroid plexus tumors (CPT) are rare pediatric tumors. A population
      based study on choroid plexus carcinoma (CPC) and choroid plexus papilloma (CPP)
      was carried out to describe the incidence, demographic, and outcome data and to
      identify potential prognostic factors. METHODS: The CPT population from the
      Canadian databank of CNS tumor in children <= 36 months diagnosed between 1990
      and 2005 was reviewed RESULTS: Out of the 579 reported cases of CNS tumors, 37
      were CPT. The annual age-adjusted incidence rate was 0.22 + 0.12 (95% CI 0.16
      0.28)/100,000 children < 3 years. There were 21 (56.7%) CPP and 16 (43.3.5%) CPC.
      Twenty patients (54%) were males. Median age at diagnosis was 7 months(range 0
      30). Ten patients(62.5%) with CPC and one with CPP were metastatic at diagnosis.
      Twenty patients with CPP (95%) had a complete resection, whereas 6/16 CPC (37.5%)
      achieved a resection >90%. Fourteen CPC patients received adjuvant chemotherapy.
      None of the 37 patients received adjuvant radiation. At completion of survey, all
      CPP and five CPC were alive. Median survival time for CPC patients was 15 months
      (0-120). One death was related to intraoperative hemorrhage, another to
      chemotherapy-induced toxicity, and one to secondary AML. Age at diagnosis, degree
      of resection and metastatic status were not significant prognostic factors for
      CPC. CONCLUSION: By contrast to CPC, CPP have an excellent prognosis following
      surgery alone. Survival of CPC remains poor. However, these data may suggest
      adjuvant chemotherapy can alter the aggressive natural history of CPC. As with
      other rare CNS tumors, international collaboration is required to identify
      optimal therapy.

PMID- 20809072
TI  - Identification of the membrane protein SucE and its role in succinate transport
      in Corynebacterium glutamicum.
AB  - Succinic acid is excreted during anaerobiosis by many bacteria, and manifold
      applications are known making the biotechnological production of succinate
      attractive. Although the pathways for succinate formation are known, succinate
      export is not understood in most of the succinate producing bacteria. Here, we
      present a bioinformatic approach for identification of a putative succinate
      export system in Corynebacterium glutamicum. The subsequent screening revealed
      that a mutant in the gene cg2425 is impaired in succinate production or transport
      under anaerobic conditions. A function of the Cg2425 protein as import system was
      excluded. In contrast, a role of the Cg2425 protein as succinate export system
      was indicated by accumulation of increased amounts of internal succinate under
      anaerobic conditions in a Cg2425-dependent manner and a concomitant impairment of
      external succinate accumulation. In conclusion, we propose that Cg2425
      participates in succinate export in C. glutamicum and suggest the name SucE for
      the protein.

PMID- 20809073
TI  - Cytosolic NADPH balancing in Penicillium chrysogenum cultivated on mixtures of
      glucose and ethanol.
AB  - The in vivo flux through the oxidative branch of the pentose phosphate pathway
      (oxPPP) in Penicillium chrysogenum was determined during growth in
      glucose/ethanol carbon-limited chemostat cultures, at the same growth rate. Non
      stationary (13)C flux analysis was used to measure the oxPPP flux. A nearly
      constant oxPPP flux was found for all glucose/ethanol ratios studied. This
      indicates that the cytosolic NADPH supply is independent of the amount of
      assimilated ethanol. The cofactor assignment in the model of van Gulik et al.
      (Biotechnol Bioeng 68(6):602-618, 2000) was supported using the published genome
      annotation of P. chrysogenum. Metabolic flux analysis showed that NADPH
      requirements in the cytosol remain nearly the same in these experiments due to
      constant biomass growth. Based on the cytosolic NADPH balance, it is known that
      the cytosolic aldehyde dehydrogenase in P. chrysogenum is NAD(+) dependent.
      Metabolic modeling shows that changing the NAD(+)-aldehyde dehydrogenase to
      NADP(+)-aldehyde dehydrogenase can increase the penicillin yield on substrate.

PMID- 20809074
TI  - Sulfur-driven autotrophic denitrification: diversity, biochemistry, and
      engineering applications.
AB  - Sulfur-driven autotrophic denitrification refers to the chemolithotrophic process
      coupling denitrification with the oxidation of reduced inorganic sulfur
      compounds. Ever since 1904, when Thiobacillus denitrificans was isolated,
      autotrophic denitrifiers and their uncultured close relatives have been
      continuously identified from highly diverse ecosystems including hydrothermal
      vents, deep sea redox transition zones, sediments, soils, inland soda lakes, etc.
      Currently, 14 valid described species within alpha-, beta-, gamma-, and epsilon
      Proteobacteria have been identified as capable of autotrophic denitrification.
      Autotrophic denitrification is also widely applied in environmental engineering
      for the removal of sulfide and nitrate from different water environments. This
      review summarizes recent researches on autotrophic denitrification, highlighting
      its diversity, metabolic traits, and engineering applications.

PMID- 20809075
TI  - Flocculation gene variability in industrial brewer's yeast strains.
AB  - The brewer's yeast genome encodes a 'Flo' flocculin family responsible for
      flocculation. Controlled floc formation or flocculation at the end of
      fermentation is of great importance in the brewing industry since it is a cost
      effective and environmental-friendly technique to separate yeast cells from the
      final beer. FLO genes have the notable capacity to evolve and diverge many times
      faster than other genes. In actual practice, this genetic variability may
      directly alter the flocculin structure, which in turn may affect the flocculation
      onset and/or strength in an uncontrolled manner. Here, 16 ale and lager yeast
      strains from different breweries, one laboratory Saccharomyces cerevisiae and one
      reference Saccharomyces pastorianus strain, with divergent flocculation
      strengths, were selected and screened for characteristic FLO gene sequences. Most
      of the strains could be distinguished by a typical pattern of these FLO gene
      markers. The FLO1 and FLO10 markers were only present in five out of the 18 yeast
      strains, while the FLO9 marker was ubiquitous in all the tested strains.
      Surprisingly, three strongly flocculating ale yeast strains in this screening
      also share a typical 'lager' yeast FLO gene marker. Further analysis revealed
      that a complete Lg-FLO1 allele was present in these ale yeasts. Taken together,
      this explicit genetic variation between flocculation genes hampers attempts to
      understand and control the flocculation behavior in industrial brewer's yeasts.

PMID- 20809076
TI  - Hybrid pseudomonads engineered by two-step homologous recombination acquire novel
      degradation abilities toward aromatics and polychlorinated biphenyls.
AB  - Pseudomonas pseudoalcaligenes KF707 possesses a chromosomally encoded bph gene
      cluster responsible for the catabolism of biphenyl and polychlorinated biphenyls.
      Previously, we constructed chimeric versions of the bphA1 gene, which encodes a
      large subunit of biphenyl dioxygenase, by using DNA shuffling between bphA1 genes
      from P. pseudoalcaligenes KF707 and Burkholderia xenovorans LB400. In this study,
      we demonstrate replacement of the bphA1 gene with chimeric bphA1 sequence within
      the chromosomal bph gene cluster by two-step homologous recombination. Notably,
      some of the hybrid strains acquired enhanced and/or expanded degradation
      capabilities for specific aromatic compounds, including single aromatic
      hydrocarbons and polychlorinated biphenyls.

PMID- 20809078
TI  - Lead toxicity in Saccharomyces cerevisiae.
AB  - The effect of Pb on Saccharomyces cerevisiae cell structure and function was
      examined. Membrane integrity was assessed by the release of UV-absorbing
      compounds and by the intracellular K(+) efflux. No leakage of UV(260)-absorbing
      compounds or loss of K(+) were observed in Pb (until 1,000 MUmol/l) treated cells
      up to 30 min; these results suggest that plasma membrane seems not to be the
      immediate and primary target of Pb toxicity. The effect of Pb on yeast metabolism
      was examined using the fluorescent probe FUN-1 and compared with the ability to
      reproduce, evaluated by colony-forming units counting. The exposition of yeast
      cells, during 60 min to 1,000 MUmol/l Pb, induces a decrease in the ability to
      process FUN-1 although the cells retain its proliferation capacity. A more
      prolonged contact time (120 min) of yeast cells with Pb induces a marked (> 50%)
      loss of yeast cells metabolic activity and replication competence through a
      mechanism which most likely requires protein synthesis.

PMID- 20809077
TI  - Field application of nitrogen and phenylacetylene to mitigate greenhouse gas
      emissions from landfill cover soils: effects on microbial community structure.
AB  - Landfills are large sources of CH(4), but a considerable amount of CH(4) can be
      removed in situ by methanotrophs if their activity can be stimulated through the
      addition of nitrogen. Nitrogen can, however, lead to increased N(2)O production.
      To examine the effects of nitrogen and a selective inhibitor on CH(4) oxidation
      and N(2)O production in situ, 0.5 M of NH(4)Cl and 0.25 M of KNO(3), with and
      without 0.01% (w/v) phenylacetylene, were applied to test plots at a landfill in
      Kalamazoo, MI from 2007 November to 2009 July. Nitrogen amendments stimulated
      N(2)O production but had no effect on CH(4) oxidation. The addition of
      phenylacetylene stimulated CH(4) oxidation while reducing N(2)O production.
      Methanotrophs possessing particulate methane monooxygenase and archaeal ammonia
      oxidizers (AOAs) were abundant. The addition of nitrogen reduced methanotrophic
      diversity, particularly for type I methanotrophs. The simultaneous addition of
      phenylacetylene increased methanotrophic diversity and the presence of type I
      methanotrophs. Clone libraries of the archaeal amoA gene showed that the addition
      of nitrogen increased AOAs affiliated with Crenarchaeal group 1.1b, while they
      decreased with the simultaneous addition of phenylacetylene. These results
      suggest that the addition of phenylacetylene with nitrogen reduces N(2)O
      production by selectively inhibiting AOAs and/or type II methanotrophs.

PMID- 20809079
TI  - Tooth desensitization with an Er:YAG laser: in vitro microscopical observation
      and a case report.
AB  - Tooth hypersensitivity is a frequent condition that causes discomfort and
      sometimes severe pain. It is caused by exposure of spots of dentinal tubules to
      the oral environment. Conventional desensitizing agents (professional pastes,
      toothpastes, mouthwashes) aim to obliterate the exposed dentinal tubules. Laser
      desensitization was introduced as an alternative efficient tool for the immediate
      treatment of tooth hypersensitivity. We explored in vitro the microscopical
      occluding effects of the Er:YAG laser on exposed dentinal tubules. The clinical
      application of this technique is also described.

PMID- 20809080
TI  - Microtensile bond strength of an etch-and-rinse adhesive to enamel and dentin
      after Er:YAG laser pretreatment with different pulse durations.
AB  - The purpose of this study is to evaluate microtensile bond strength (MUTBS) of an
      etch-and-rinse adhesive to enamel and dentin after treatment with Er:YAG laser
      using different pulse durations. Extracted human molars were flattened to obtain
      enamel or dentin surfaces. The enamel specimens (E) were divided into nine groups
      and the dentin (D) specimens were divided into seven groups according to the
      surface treatments (n = 6). E-C: acid was applied according to the manufacturer's
      instructions and used as control, E-SSP: 120 mJ, 10 Hz, SSP (50 MUs), E-SSP-A:
      120 mJ,10 Hz, SSP+acid, E-VSP: 120 mJ, 10 Hz, VSP (100 MUs), E-VSP-A: 120 mJ, 10
      Hz, VSP+acid, E-SP: 120 mJ, 10 Hz, SP (150 MUs), E-SP-A:120 mJ,10 Hz, SP+acid, E
      LP:120 mJ,10 Hz, LP (300 MUs), E-LP-A:120 mJ,10 Hz, LP+acid; D-C: acid was
      applied and used as control, D-SSP: 80 mJ, 10 Hz, SSP, D-SSP-A: 80 mJ, 10 Hz,
      SSP+acid, D-VSP: 80 mJ, 10 Hz, VSP, D-VSP-A: 80 mJ, 10 Hz, VSP+acid, D-SP: 80 mJ,
      10 Hz, SP, D-SP-A: 80 mJ, 10 Hz, SP+acid. After application of etch-and-rinse
      adhesive, composite built-ups were created with a nanoceramic composite.
      Specimens were sectioned into serial 1-mm(2) sticks, and MUTBS was measured in
      five sticks from each tooth randomly selected (n = 30). Failure modes were
      determined under a stereomicroscope. MUTBS test data were analyzed by Welch-ANOVA
      followed by Dunnett's T3 tests and failure mode distributions were analyzed by
      Pearson Chi-square test (p = 0.05). MUTBS was higher for enamel and dentin after
      additional acid etching than laser irradiation alone. E-SSP-A group exhibited the
      highest MUTBS for enamel (p < 0.05). The D-SP-A group showed the highest value
      but the difference was not significant in comparison to D-C (p > 0.05). The MUTBS
      of laser-irradiated but not acid-etched groups decreased when longer pulse
      durations were used. Laser treatment could enhance or impair the MUTBS to enamel
      and dentin depending on the pulse duration used and additional acid application.

PMID- 20809081
TI  - Bactericidal effect of a Nd:YAG laser on Enterococcus faecalis at pulse durations
      of 15 and 25 ms in dentine depths of 500 and 1,000 MUm.
AB  - The success of endodontic treatment depends on the effective elimination of
      microorganisms from the root canal, and lasers provide more effective
      disinfection than conventional treatment using rinsing solutions. The objective
      of this in vitro study was to determine the bactericidal effect of laser
      irradiation in dentine of various depths at a wavelength of 1,064 nm and pulse
      durations of 15 and 25 ms. A total of 90 dentine slices were cut from bovine
      incisors and divided into two groups (45 slices each) of thickness 500 and 1,000
      MUm. All were inoculated with a suspension of Enterococcus faecalis (5.07 * 10(9)
      bacteria/ml). Based on the clinically accepted dose (approximately 300 J/cm(2)),
      the following laser settings were chosen for this study: 1.75 W, 0.7 Hz for 4 s,
      three repetitions. The two groups were divided into two subgroups of 15 slices
      each to be irradiated with pulse durations of 15 and 25 ms. The remaining 15
      slices per group were not irradiated to serve as a control. After irradiation,
      the colony-forming units (CFU) were counted and evaluated. To determine the
      bactericidal effect of irradiation with different pulse durations, the results in
      the different groups were compared statistically. For all irradiated subgroups a
      bactericidal effect was observed at pulse durations of 15 and 25 ms (p=0.0085 and
      p<0.0001). The corresponding average log kills were 0.29 (15 ms) and 0.52 (25 ms)
      for 500 MUm and 0.15 and 0.3 for 1,000 MUm, respectively. The results of this in
      vitro study showed that Nd:YAG laser irradiation with a pulse duration of 15 ms
      eliminated an average of 49% and 29% of E. faecalis at dentine depths of 500 MUm
      and 1,000 MUm, respectively, and irradiation with a pulse duration of 25 ms
      eliminated 70% (500 MUm) and 50% (1,000 MUm). However, these values are lower
      than those achieved with the established protocol using microsecond pulses.

PMID- 20809082
TI  - Status epilepticus attributed to moxifloxacin in an adolescent patient with spina
      bifida occulta.

PMID- 20809083
TI  - Prevalence of hypothyroidism in Finland--a nationwide prescription study.
AB  - PURPOSE: The aim of this study was to estimate the 1-year prevalence of
      levothyroxine-treated hypothyroidism in Finland. METHODS: Data on all individuals
      who had regularly purchased levothyroxine sodium tablets during 2007 were
      retrieved from the nationwide Finnish Drug Prescription Database. The prevalence
      rates and 95% confidence intervals were calculated per 100 individuals assuming a
      Poisson distribution. RESULTS: In total, 189,027 individuals (84% female) were
      identified as using levothyroxine tablets, which translated into a 1-year
      prevalence of hypothyroidism of 3.6%. The disease was notably more common in
      females (5.9%) than in males (1.2%), with a gender prevalence rate ratio (PRR) of
      4.5. Prevalence increased with age. A comparison of five university hospital
      districts revealed that the prevalence rates were fairly stable regionally, with
      the lowest rate being 3.1% and the highest 4.4%; the regional PRR was 1.3.
      CONCLUSIONS: To the best of our knowledge, this nationwide prescription study
      includes the largest population of reported levothyroxine users to date. This
      comprehensive data justifies estimating the gender- and age-specific prevalence
      of hypothyroidism in Finland.

PMID- 20809084
TI  - Association analysis of SLC30A8 rs13266634 and rs16889462 polymorphisms with type
      2 diabetes mellitus and repaglinide response in Chinese patients.
AB  - OBJECTIVE: Genome-wide association studies (GWASs) identified that SLC30A8
      genetic polymorphism was a risk of type 2 diabetes mellitus (T2DM) in several
      populations. This study aimed to investigate whether the SLC30A8 rs13266634 and
      rs16889462 polymorphisms were associated with T2DM susceptibility and repaglinide
      therapeutic efficacy in Chinese T2DM patients. METHODS: We conducted a case
      control study of 443 T2DM patients and 229 healthy volunteers to identify SLC30A8
      rs13266634 and rs16889462 genotypes by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) assay. Forty-eight patients were randomly
      selected and underwent an 8-week repaglinide treatment (3 mg/d). Fasting plasma
      glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbAlc),
      fasting serum insulin (FINS), postprandial serum insulin (PINS), homeostasis
      model assessment for insulin resistance (HOMA-IR), serum triglyceride, total
      cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c) and high-density
      lipoprotein-cholesterol (HDL-c) were determined before and after repaglinide
      treatment. RESULTS: SLC30A8 rs13266634 risk C allele frequency was higher in T2DM
      patients than in healthy controls (P < 0.05). There was a better repaglinide
      response on FINS (P < 0.05) and PINS (P < 0.01) in patients with rs13266634 CT+TT
      genotypes compared with CC genotype carriers. Patients with rs16889462 GA
      genotype showed an enhanced repaglinide efficacy on FPG (P < 0.01), PPG (P <
      0.01) and HbAlc (P < 0.05) compared with GG genotype individuals. CONCLUSIONS:
      SLC30A8 rs13266634 and rs16889462 polymorphisms were associated with repaglinide
      therapeutic efficacy in Chinese T2DM patients.

PMID- 20809086
TI  - Predisposition of cows to mastitis in non-infected mammary glands: effects of
      dietary-induced negative energy balance during mid-lactation on immune-related
      genes.
AB  - Cows experiencing severe postpartal negative energy balance (NEB) are at greater
      risk of developing mastitis than cows in positive energy balance (PEB). Our
      objectives were to compare mammary tissue gene expression profiles between
      lactating cows (n = 5/treatment) subjected to feed restriction to induce NEB and
      cows fed ad libitum to maintain PEB in order to identify genes involved in immune
      response and cellular metabolism that may predispose cows to an intramammary
      infection in non-infected mammary gland. The NEB cows were feed-restricted to 60%
      of calculated net energy for lactation requirements, and cows fed PEB cows were
      fed the same diet ad libitum. At 5 days after feed restriction, one rear mammary
      gland from all cows was biopsied for RNA extraction and transcript profiling
      using microarray and quantitative PCR. Energy balance (NEB vs. PEB) resulted in
      278 differentially expressed genes (DEG). Among up-regulated DEG (n = 180),
      Ingenuity Pathway Analysis(r) identified lipid metabolism (8) and molecular
      transport (14) as some of the most enriched molecular functions. Genes down
      regulated by NEB (98) were associated with cell growth and proliferation (21) and
      cell death (18). Results indicate that DEG due to NEB in mid-lactation were
      associated with numerous biological functions but we did not identify genes that
      could, a priori, be associated with risk of intramammary infection in non
      infected mammary glands. Further studies with early postpartal cows are required.

PMID- 20809085
TI  - Sulbutiamine counteracts trophic factor deprivation induced apoptotic cell death
      in transformed retinal ganglion cells.
AB  - Sulbutiamine is a highly lipid soluble synthetic analogue of vitamin B(1) and is
      used clinically for the treatment of asthenia. The aim of our study was to
      demonstrate whether sulbutiamine is able to attenuate trophic factor deprivation
      induced cell death to transformed retinal ganglion cells (RGC-5). Cells were
      subjected to serum deprivation for defined periods and sulbutiamine at different
      concentrations was added to the cultures. Various procedures (e.g. cell viability
      assays, apoptosis assay, reactive oxygen species analysis, Western blot analysis,
      flow cytometric analysis, glutathione (GSH) and glutathione-S-transferase (GST)
      measurement) were used to demonstrate the effect of sulbutiamine. Sulbutiamine
      dose-dependently attenuated apoptotic cell death induced by serum deprivation and
      stimulated GSH and GST activity. Moreover, sulbutiamine decreased the expression
      of cleaved caspase-3 and AIF. This study demonstrates for the first time that
      sulbutiamine is able to attenuate trophic factor deprivation induced apoptotic
      cell death in neuronal cells in culture.

PMID- 20809087
TI  - Association of COX-2 promoter polymorphism with gastrointestinal tract cancer in
      Iran.

PMID- 20809088
TI  - Empowering self-renewal and differentiation: the role of mitochondria in stem
      cells.
AB  - Stem cells are characterized by their multi-lineage differentiation potential
      (pluripotency) and their ability for self-renewal, which permits them to
      proliferate while avoiding lineage commitment and senescence. Recent studies
      demonstrate that undifferentiated, pluripotent stem cells display lower levels of
      mitochondrial mass and oxidative phosphorylation, and instead preferentially use
      non-oxidative glycolysis as a major source of energy. Hypoxia is a potent
      suppressor of mitochondrial oxidation and appears to promote "stemness" in adult
      and embryonic stem cells. This has lead to an emerging paradigm, that
      mitochondrial oxidative metabolism is not just an indicator of the
      undifferentiated state of stem cells, but may also regulate the pluripotency and
      self-renewal of stem cells. The identification of specific mitochondrial pathways
      that regulate stem cell fate may therefore enable metabolic programming and
      reprogramming of stem cells.

PMID- 20809089
TI  - Tailor-made inflammation: how neutrophil serine proteases modulate the
      inflammatory response.
AB  - Neutrophil granulocytes are important mediators of innate immunity, but also
      participate in the pathogenesis of (auto)inflammatory diseases. Neutrophils
      express a specific set of proteolytic enzymes, the neutrophil serine proteases
      (NSPs), which are stored in cytoplasmic granules and can be secreted into the
      extra- and pericellular space upon cellular activation. These NSPs, namely
      cathepsin G (CG), neutrophil elastase (NE), and proteinase 3 (PR3), have early
      been implicated in bacterial defense. However, NSPs also regulate the
      inflammatory response by specifically altering the function of cytokines and
      chemokines. For instance, PR3 and NE both inactivate the anti-inflammatory
      mediator progranulin, which may play a role in chronic inflammation. Here, we
      provide a concise update on NSPs as modulators of inflammation and discuss the
      biological and pathological significance of this novel function of NSPs. Mounting
      evidence support an important proinflammatory function for PR3, which may have
      been underestimated in the past.

PMID- 20809091
TI  - Cost-effectiveness of zoledronic acid in the prevention of skeletal-related
      events in patients with bone metastases secondary to advanced renal cell
      carcinoma: application to France, Germany, and the United Kingdom.
AB  - BACKGROUND: The use of zoledronic acid (ZOL) has recently been shown to
      significantly reduce the risk of new skeletal-related events (SREs) in renal cell
      carcinoma (RCC) patients with bone metastases. The present exploratory study
      assessed the cost-effectiveness of ZOL in this population, adopting a French,
      German, and United Kingdom (UK) government payer perspective. MATERIALS AND
      METHODS: This cost-effectiveness model was based on a post hoc retrospective
      analysis of a subset of patients with RCC who were included in a larger
      randomized clinical trial of patients with bone metastases secondary to a variety
      of cancers. In the trial, patients were randomized to receive ZOL (n = 27) or
      placebo (n = 19) with concomitant antineoplastic therapy every 3 weeks for 9
      months (core study) plus 12 months during a study extension. Since the trial did
      not collect costs or data on the quality-adjusted life years (QALYs) of the
      patients, these outcomes had to be assumed via modeling exercises. The costs of
      SREs were estimated using hospital DRG tariffs. These estimates were supplemented
      with literature-based costs where possible. Drug, administration, and supply
      costs were obtained from published and internet sources. Consistent with similar
      economic analyses, patients were assumed to experience quality of life decrements
      lasting 1 month for each SRE. Uncertainty surrounding outcomes was addressed via
      multivariate sensitivity analyses. RESULTS: Patients receiving ZOL experienced
      1.07 fewer SREs than patients on placebo. Patients on ZOL experienced a gain in
      discounted QALYs of approximately 0.1563 in France and Germany and 0.1575 in the
      UK. Discounted SRE-related costs were substantially lower among ZOL than placebo
      patients (-? 4,196 in France, - ? 3,880 in Germany, and -? 3,355 in the UK).
      After taking into consideration the drug therapy costs, ZOL saved ? 1,358, ?
      1,223, and ? 719 in France, Germany, and the UK, respectively. In the
      multivariate sensitivity analyses, therapy with ZOL saved costs in 67-77% of
      simulations, depending on the country. The cost per QALY gained for ZOL versus
      placebo was below ? 30,000 per QALY gained threshold in approximately 93-94% of
      multivariate sensitivity analyses simulations. CONCLUSIONS: The present analysis
      suggests that ZOL saves costs and increases QALYs compared to placebo in French,
      German, and UK RCC patients with bone metastases. Additional prospective research
      may be needed to confirm these results in a larger sample of patients.

PMID- 20809092
TI  - The impact of repeated cost containment policies on pharmaceutical expenditure:
      experience in Spain.
AB  - The growth in expenditure on the financing of pharmaceuticals is a factor that
      accounts for a large part of the increase in public health spending in most
      developed countries. In an attempt to kerb this growth, many health authorities,
      particularly in Europe, have introduced numerous regulatory measures that have
      affected the market, especially on the supply side. These measures include the
      system of reference pricing, the reduction of wholesale distributors' and
      retailers' markups and compulsory reductions of ex-factory prices. We assess the
      impact of these cost containment measures on expenditure per capita,
      prescriptions per capita and the average price of pharmaceuticals financed by the
      public sector in Catalonia (Spain), from 1995 to 2006. We apply an autoregressive
      integrated moving average (ARIMA) time series model using dummy variables to
      represent the various cost containment measures implemented. Twelve of the 16
      interventions analysed that were intended to contain the overall pharmaceutical
      expenditure were not effective in reducing it even in the short term, and the
      four that were effective were not so in the long term, thus amounting to a
      moderate annual saving.

PMID- 20809090
TI  - The role of nucleotides in apoptotic cell clearance: implications for disease
      pathogenesis.
AB  - Apoptosis occurs in many tissues, during both normal and pathogenic processes.
      Normally, apoptotic cells are rapidly cleared, either by neighboring or recruited
      phagocytes. The prompt clearance of apoptotic cells requires that the apoptotic
      cells announce their presence through the release of chemotactic factors, known
      as "find-me" signals, to recruit phagocytes to the site of death, and through the
      exposure of so-called "eat-me" signals, which are ligands for phagocytic uptake.
      The importance of prompt apoptotic cell clearance is revealed by findings that
      decreasing the efficiency of engulfment results in the persistence of apoptotic
      cells, which is often associated with chronic inflammation and autoimmunity.
      Additionally, the proper clearance of apoptotic cells is actively anti
      inflammatory, which is thought to play a crucial role in immunologic tolerance.
      Therefore, defects associated with clearance of apoptotic cells may contribute to
      the pathogenesis of several inflammatory diseases, including autoimmunity and
      atherosclerosis. Here, we review the role of nucleotides in the apoptotic cell
      clearance process and discuss their implications for disease pathogenesis.

PMID- 20809094
TI  - Reviewer's comment on "five-year outcome of surgical decompression of the lumbar
      spine without fusion" by Mannion AF, Denzler R, Dvorak J, Grob D
      (doi:10.1007/s00586-010-1535-2).

PMID- 20809093
TI  - Amaurosis after spine surgery: survey of the literature and discussion of one
      case.
AB  - Postoperative vision loss (POVL) associated with spine surgery is a well known,
      albeit very rare complication. POVL incidence after spinal surgery ranges from
      0.028 to 0.2%; however, due to the increase in number and duration of annual
      complex spinal operations, the incidence may increase. Origin and pathogenesis of
      POVL remain frequently unknown. A 73-year-old patient presented with lumbar disc
      herniation with associated neurological deficits after conservative pre-treatment
      at a peripheral hospital. Known comorbidities included arterial hypertension,
      moderate arterial sclerosis, diabetes mellitus type 2, mildly elevated blood
      lipids and treated prostate gland cancer. During lumbar spine surgery in modified
      prone position the patient presented with an acute episode of severe hypotension,
      which required treatment with catecholamines and Trendelenburg positioning. Three
      hours postoperatively, a visual loss in the right eye occurred, resulting in a
      complete amaurosis. Antihypertensive medication, arteriosclerosis and
      intraoperative hypotension are possible causes for the POVL. Intraoperative
      administration of catecholamines and Trendelenburg positioning for treatment of
      systemic hypotension might further compromise ocular perfusion. In patients with
      comorbidities compromising arterial blood pressure, blood circulation and
      microcirculation, POVL must be considered as a severe postoperative complication.
      It is recommended to inform patients about such complications and obtain
      preoperative informed consent regarding POVL. Any recent modification of
      antihypertensive medication must be reported and analysed for potential
      intraoperative hemodynamic consequences, prior to spine surgery in prone
      position.

PMID- 20809095
TI  - Advancing molecular imaging: a chairman's perspective on how radiology can meet
      the challenge.
AB  - To date, most molecular imaging techniques applied clinically have offered
      relatively general information about the metabolism and physiology of diseased
      cells and tissues. However, due to recent scientific and technological advances,
      much more specifically targeted molecular imaging probes (e.g., reporter gene
      probes, whole cell-tracking probes, and probes for localizing specific
      biomolecules) are now being used in preclinical research and, in some cases,
      translated to the clinical setting. As a result, the imaging community is poised
      to help lead a revolution in personalized, molecularly targeted medicine. This
      article considers the importance of molecular imaging for advancing research and
      clinical care both within individual institutions and across the medical field.
      It outlines specific steps that leaders in academic radiology can take to hasten
      progress in molecular imaging and explains why they must have the courage to
      reach across traditional interdisciplinary boundaries and advocate for major
      investments in equipment, education, and personnel.

PMID- 20809096
TI  - Effect of risedronate on osteocyte viability and bone turnover in paired iliac
      bone biopsies from early postmenopausal women.
AB  - It is unclear whether standard clinical doses of risedronate affect osteocyte
      viability. This study examined osteocyte viability and bone remodeling rate in
      early postmenopausal women (1-5 years after menopause) who were treated with a
      standard clinical dose of risedronate (5 mg/day, orally) for 1 year. Paired
      transiliac bone biopsies were obtained from 19 postmenopausal women at baseline
      and after 1-year treatment with placebo (n = 8, mean age 52.9 +/- 3.4 years) or
      risedronate 5 mg/day (n = 11, mean age 52.5 +/- 3.4 years). In these samples, we
      measured osteocyte- and bone remodeling-related variables in trabecular bone. In
      both the placebo and risedronate groups, empty lacunae were significantly
      decreased after 1-year treatment compared to baseline. There were no significant
      differences in osteocyte-related variables between placebo and risedronate.
      Risedronate significantly reduced bone-remodeling indices including mineralizing
      surface (MS/BS), bone formation rate (BFR/BS), and activation frequency (Ac.f).
      Risedronate treatment caused significantly lower MS/BS and Ac.f than placebo
      administration. In conclusion, risedronate 5 mg/day effectively inhibited bone
      remodeling but did not significantly reduce osteocyte viability in trabecular
      bone.

PMID- 20809097
TI  - Markesbery disease: autosomal dominant late-onset distal myopathy: from phenotype
      to ZASP gene identification.
AB  - In 1974, Markesbery et al. thoroughly characterized and reported a large kindred
      with distal muscle weakness of late adult-onset that was autosomal dominantly
      inherited. Clinical evidence supported myopathy rather than the usual neuropathy
      expected with distal weakness. Postmortem examination of two patients documented
      myopathy and excluded anterior horn cell disease or peripheral neuropathy as the
      cause. Distinctive morphologic changes were present in muscle. Widely accepted as
      a distinct disease entity, this disorder has recently been characterized as one
      of a group of myofibrillar myopathies resulting from mutations in several muscle
      proteins. Studies of members of the original family have now identified the
      molecular defect to be a mutation in ZASP, Z-band alternatively spliced PDZ-motif
      containing protein. The specific mutation, A165V, was identified in all clinical
      affected family members by direct sequencing. Thus, Markesbery disease is a
      zaspopathy. Other families have been identified with the same mutation and a
      shared haplotype indicating a founder effect.

PMID- 20809098
TI  - Amino acid sequence analysis and identification of mutations under positive
      selection in hemagglutinin of 2009 influenza A (H1N1) isolates.
AB  - The 2009 flu pandemic is caused by a new strain of influenza A (H1N1) virus,
      A/H1N1/09. With its high transmissibility, this novel virus has caused a pandemic
      and infected over 600,000 people globally. By comparing the hemagglutinin (HA)
      gene and protein sequences among over 700 A/H1N1/09 isolates, mutations in the
      receptor-binding sites and antigenic epitope regions were identified. Among these
      mutations, T220 and E/G239 were found to be strongly positively selected over the
      course of spreading of the A/H1N1/09 virus worldwide. Interestingly, both sites
      are located in the highly variable epitope regions of HA1, and residue 239 also
      plays an important role in the receptor-binding process. Further analyses
      demonstrated that the percentage of T220 mutants among all isolates increased
      rapidly during the evolution, and that an E/G239 mutation could decrease the
      binding affinity of the virus with its cellular receptor. Thus, due to a
      potential functional importance of residues 220 and 239, mutations at these
      sites, as well as the significant of positive selection on these sites deserves
      more attention, while new vaccines and therapeutic drugs are developed against
      this novel virus.

PMID- 20809099
TI  - Fourteen non-CODIS autosomal short tandem repeat loci multiplex data from
      Taiwanese.
AB  - Interest in the development of polymorphic short tandem repeat (STR) markers
      unlinked to the CODIS loci is growing among forensic practitioners. We developed
      a multiplex system in which14 autosomal STR (D3S1744, D4S2366, D8S1110, D12S1090,
      D13S765, D14S608, Penta E, D17S1294, D18S536, D18S1270, D20S470, D21S1437, Penta
      D, and D22S683) could be amplified in one single polymerase chain reaction. DNA
      samples from 572 unrelated Taiwanese Han subjects were analyzed using this 14 STR
      multiplex system. Thirty parent-child pairs of parentage testing cases with a
      combined paternity index (CPI) below 1,000 and 32 parent-child pairs with single
      step mutations found in AmpFlSTR Identifiler loci were also recruited for
      validation of the newly developed system. DNA sequencing was performed for novel
      STRs and novel alleles found in these subjects. The distributions of allelic
      frequencies for these autosomal STRs and sequence data, allele nomenclature for
      the STRs, and forensic parameters are presented. The discrimination power in our
      multiplex loci ranged from 0.6858 (D18S536) to 0.9168 (Penta E), with a combined
      discrimination power of 0.999999999. It provides additional power to distinguish
      the possible single-step mutations in parent-child pairs and improves the ability
      to prove parentage by increasing the CPI. The combined power of exclusion of
      these 14 loci in Taiwanese Han in this study was 0.9999995913. In conclusion,
      this 14-autosomal STRs multiplex system provides highly informative STR data and
      appears useful in forensic casework and parentage testing.

PMID- 20809101
TI  - Freiburg neuropathology case conference: a medial temporal lobe lesion.

PMID- 20809102
TI  - Parenting in emerging adulthood: an examination of parenting clusters and
      correlates.
AB  - The changing nature of the transition to adulthood in western societies, such as
      the United States, may be extending the length of time parents are engaged in
      "parenting" activities. However, little is known about different approaches
      parents take in their interactions with their emerging-adult children. Hence,
      this study attempted to identify different clusters of parents based on the
      extent to which they exhibited both extremes of control (psychological control,
      punishment, verbal hostility, indulgence) and responsiveness (knowledge, warmth,
      induction, autonomy granting), and to examine how combinations of parenting were
      related to emerging adult children's relational and individual outcomes (e.g.
      parent-child relationship quality, drinking, self-worth, depression). The data
      were collected from 403 emerging adults (M age = 19.89, SD = 1.78, range = 18-26,
      62% female) and at least one of their parents (287 fathers and 317 mothers).
      Eighty-four percent of participants reported being European American, 6% Asian
      American, 4% African American, 3% Latino, and 4% reported being of other
      ethnicities. Data were analyzed using hierarchical cluster analysis, separately
      for mothers and fathers, and identified three similar clusters of parents which
      we labeled as uninvolved (low on all aspects of parenting), controlling-indulgent
      (high on both extremes of control and low on all aspects of responsiveness), and
      authoritative (high on responsiveness and low on control). A fourth cluster was
      identified for both mothers and fathers and was labeled as inconsistent for
      mothers (mothers were above the mean on both extremes of control and on
      responsiveness) and average for fathers (fathers were at the mean on all eight
      aspects of parenting). The discussion focuses on how each of these clusters
      effectively distinguished between child outcomes.

PMID- 20809103
TI  - Kinetic analysis and modeling of daptomycin batch fermentation by Streptomyces
      roseosporus.
AB  - In this study, Streptomyces roseosporus was subjected to helium-neon (He-Ne)
      laser (632.8 nm) irradiation to improve the production ability of extracellular
      antibiotic daptomycin. Under the optimum irradiation dosage of 18 mW for 22 min,
      a stable positive mutant strain S. roseosporus LC-54 was obtained. The maximum
      A21978C (daptomycin is a semisynthetic antimicrobial substance derived from the
      A21978C complex) yield of this mutant strain was 296 mg/l, which was 146% higher
      than that of the wild strain. The mutant strain grew more quickly and utilized
      carbohydrate sources more efficiently than the wild strain. The batch culture
      kinetics was investigated in a 7 l bioreactor. The logistic equation for growth,
      the Luedeking-Piret equation for daptomycin production, and Luedeking-Piret-like
      equations for carbon substrate consumption were established. This model appeared
      to provide a reasonable description for each parameter during the growth phase
      and fitted fairly well with the experiment data.

PMID- 20809104
TI  - The appearance of dermcidin isoform 2, a novel platelet aggregating agent in the
      circulation in acute myocardial infarction that inhibits insulin synthesis and
      the restoration by acetyl salicylic acid of its effects.
AB  - Hyperglycemia with severe reduction of plasma insulin level is frequently
      associated with acute ischemic heart disease. Since insulin is reported to be an
      anti thrombotic humoral factor, the mechanism of the impaired insulin synthesis
      was investigated. The plasma from the patients with acute myocardial infarction
      (AMI) was analyzed by SDS-polyacrylamide gel electrophoresis. Dermcidin isoform 2
      (dermcidin) was determined by enzyme linked immunosorbent assay. Insulin
      synthesis was determined by in vitro translation of glucose induced insulin mRNA
      synthesis in the pancreatic beta cells. Nitric oxide (NO) was determined by
      methemoglobin method. SDS-polyacrylamide gel electrophoresis of AMI plasma
      demonstrated the presence of a novel protein band of Mr 11 kDa that was
      determined to be dermcidin. Addition of 0.1 MUM dermcidin inhibited insulin
      synthesis by >65 fold compared to control through the inhibition of NO synthesis
      in the pancreatic cells. The oral administration of 150 mg acetyl salicylic acid
      (aspirin) to the AMI patients increased the plasma insulin level from 13 (median)
      to 143 MUunits/dl (median) with concomitant decrease of plasma dermcidin level
      from 112 to 9 nM in these patients within 12 h. It was also found that while the
      injection of 3.0 +/- 0.05 (n = 10) nmol dermcidin with 0.25 +/- 0.03 MUmol ADP/g
      body weight caused coronary thrombus in mice, ADP itself at this concentration
      failed to produce thrombus. These results indicated that dermcidin was a novel
      platelet aggregating agent, and potentiated the ADP induced thrombosis in the
      animal model as well as acutely inhibited glucose induced insulin synthesis.

PMID- 20809105
TI  - Potential malaria outbreak in Germany due to climate warming: risk modelling
      based on temperature measurements and regional climate models.
AB  - PURPOSE: Climate warming can change the geographic distribution and intensity of
      the transmission of vector-borne diseases such as malaria. The transmitted
      parasites usually benefit from increased temperatures as both their reproduction
      and development are accelerated. Lower Saxony (northwestern Germany) has been a
      malaria region until the 1950s, and the vector species are still present
      throughout Germany. This gave reason to investigate whether a new autochthonous
      transmission could take place if the malaria pathogen was introduced again in
      Germany. MATERIALS AND METHODS: The spatial distribution of potential temperature
      driven malaria transmissions was investigated using the basic reproduction rate
      (R (0)) to model and geostatistically map areas at risk of an outbreak of tertian
      malaria based on measured (1961-1990, 1991-2007) and predicted (1991-2020, 2021
      2050, 2051-2080) monthly mean air temperature data. RESULTS: From the
      computations, maps were derived showing that during the period 1961-1990, the
      seasonal transmission gate ranges from 0 to 4 months and then expands up to 5
      months in the period 1991-2007. For the projection of future trends, the regional
      climate models REMO and WettReg were used each with two different scenarios (A1B
      and B1). Both modelling approaches resulted in prolonged seasonal transmission
      gates in the future, enabling malaria transmissions up to 6 months in the climate
      reference period 2051-2080 (REMO, scenario A1B). DISCUSSION: The presented risk
      prognosis is based on the R (0) formula for the estimation of the reproduction of
      the malaria pathogen Plasmodium vivax. The presented model focuses on mean air
      temperatures; thus, other driving factors like the distribution of water bodies
      (breeding habitats) or population density are not integrated. Nevertheless, the
      modelling presented in this study can help identify areas at risk and initiate
      prevention. The described findings may also help in the investigation and
      assessment of related diseases caused by temperature-dependent vectors and
      pathogens, including those being dangerous for livestock as well, e.g. insect
      borne bluetongue disease transmitted by culicoids.

PMID- 20809107
TI  - Difference in the effects of tandospirone on ataxia in various types of
      spinocerebellar degeneration: an open-label study.
AB  - The aim of this study was to investigate the effects of tandospirone on ataxia in
      various types of spinocerebellar degeneration (SCD). Fifteen milligram per day of
      tandospirone was administered to 39 patients with SCD (spinocerebellar atrophy
      (SCA) 1, five patients; SCA2, six patients; Machado-Joseph disease (MJD), 14
      patient; SCA6, five patients; multiple system atrophy-cerebellar type (MSA-C),
      seven patients; and multiple system atrophy-Parkinson type (MSA-P), two
      patients). All patients were assessed before and 4 weeks after administration of
      the drug using the international cooperative ataxia rating scale total score
      (ARS), total length traveled (TLT) of body stabilometry, and a self-rating
      depression scale. Statistically, ARS showed a significant difference in MJD (p =
      0.005) and SCA6 (p = 0.043). TLT also showed a significant difference in MJD (p =
      0.002) and SCA6 (p = 0.043). Eight of 39 patients (SCA1, 1/5; SCA2, 0/6; MJD,
      4/14; SCA6, 3/5; MSA-C, 0/7; and MSA-P, 0/2) showed more than a five point
      reduction in ARS, and 13 of 39 patients (SCA1, 0/5; SCA2, 1/6; MJD, 8/14; SCA6,
      4/5; MSA-C, 0/7; and MSA-P, 0/2) showed a reduction of TLT. Our data indicate
      that the effects of tandospirone on ataxia are different between types of SCD.
      Therefore, tandospirone is useful for cerebellar ataxia in patients with MJD and
      SCA6.

PMID- 20809106
TI  - Visuomotor cerebellum in human and nonhuman primates.
AB  - In this paper, we will review the anatomical components of the visuomotor
      cerebellum in human and, where possible, in non-human primates and discuss their
      function in relation to those of extracerebellar visuomotor regions with which
      they are connected. The floccular lobe, the dorsal paraflocculus, the oculomotor
      vermis, the uvula-nodulus, and the ansiform lobule are more or less independent
      components of the visuomotor cerebellum that are involved in different
      corticocerebellar and/or brain stem olivocerebellar loops. The floccular lobe and
      the oculomotor vermis share different mossy fiber inputs from the brain stem; the
      dorsal paraflocculus and the ansiform lobule receive corticopontine mossy fibers
      from postrolandic visual areas and the frontal eye fields, respectively. Of the
      visuomotor functions of the cerebellum, the vestibulo-ocular reflex is controlled
      by the floccular lobe; saccadic eye movements are controlled by the oculomotor
      vermis and ansiform lobule, while control of smooth pursuit involves all these
      cerebellar visuomotor regions. Functional imaging studies in humans further
      emphasize cerebellar involvement in visual reflexive eye movements and are
      discussed.

PMID- 20809108
TI  - Elevated serum anti-mullerian hormone in adolescent and young adult Chinese
      patients with polycystic ovary syndrome.
AB  - PURPOSES: To explore the serum anti-mullerian hormone (AMH) level in adolescent
      and young adult Chinese patients with polycystic ovary syndrome (PCOS), and to
      evaluate its diagnostic value for PCOS. STUDY DESIGN: Serum AMH was measured in a
      cohort of 47 adolescent and young adult Chinese patients with PCOS and 40 age
      matched controls. Its diagnostic potential was evaluated by Receiver Operating
      Characteristic (ROC) curves. RESULTS: The serum AMH level was higher in PCOS
      patients than in controls (9.85 +/- 4.93 ng/mL vs. 7.13 +/- 3.02 ng/mL, P =
      0.002), and positively related to the mean ovarian volume in PCOS patients (r =
      0.319, P = 0.029). The area under the ROC curve for AMH reached a value of 0.664
      (0.551-0.778, 95% confidence interval). The best compromise between specificity
      (70%) and sensitivity (61.7%) was obtained with a cut-off value of 8 ng/mL.
      CONCLUSIONS: Serum AMH levels are elevated in adolescent and young adult Chinese
      patients of PCOS. Serum AMH measurement offers a relatively poor diagnostic
      potency with a sensitivity of 61.7% and a specificity of 70% at 8 ng/mL.

PMID- 20809109
TI  - Membranoproliferative glomerulonephritis following allogeneic hematopoietic stem
      cell transplantation.
AB  - Nephrotic syndrome after allogeneic hematopoietic stem cell transplantation has
      been increasingly described as a manifestation of chronic graft-versus-host
      disease (GVHD); however, GVHD-associated membranoproliferative glomerulonephritis
      is extremely rare. A 44-year-old man developed nephrotic syndrome 24 months after
      HSCT for acute lymphoblastic leukemia. The renal biopsy showed type I
      membranoproliferative glomerulonephritis. Salivary gland biopsy demonstrated mild
      lymphocytic infiltration, indicating chronic GVHD. Improvement of the proteinuria
      and recovery of renal function were achieved within 11 months of treatment with
      oral prednisolone and azathioprine.

PMID- 20809111
TI  - Prophylactic antibiotic trends in transsphenoidal surgery for pituitary lesions.
AB  - Pituitary surgery involves operating in the nasal cavity, which is considered a
      clean-contaminated wound. In the absence of evidence-based guidelines for
      preventing surgical site infections in trans-sphenoidal surgery, a survey of
      current opinion on prophylactic antibiotics might help elucidate the current
      acceptable practices and identify opportunities for prospective clinical trials
      that could lead to the development of practice guidelines. An on-line, 10
      question, multiple-choice survey was distributed by e-mail link to the membership
      of the International Society of Pituitary Surgeons. Sixty-nine members responded
      to the survey. Ninety-one percent indicated that there was no strong evidence
      supporting antibiotic use, but 81% used them to be safe. Ninety percent of
      respondents used intravenous prophylactic antibiotics, while only 16% used
      intranasal antibiotics. The most commonly used antibiotics were cephalosporins
      (72%) and penicillins (21%). Seventy-six percent used antibiotics for 24 h or
      less after surgery. The most commonly reported indications for prophylactic
      antibiotics were prevention of meningitis and sinusitis. The results of the
      survey describe current acceptable practices for chemoprophylaxis in patients
      undergoing transsphenoidal pituitary surgery.

PMID- 20809110
TI  - Association between cystatin C and inflammation in patients with essential
      hypertension.
AB  - BACKGROUND: Serum cystatin C is not only a marker of renal function but also acts
      as an independent risk factor for cardiovascular damage, heart failure, and
      death. It is known that the initiation and progression of these cardiovascular
      events contributes to renal dysfunction and chronic inflammation. In this study,
      we investigated the relationship between cystatin C and proinflammatory
      cytokines. METHODS: Eighty-eight patients with essential hypertension
      participated in the study, which involved measuring proinflammatory cytokines,
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and C reactive protein
      (CRP). RESULTS: Positive correlations were detected between cystatin C and
      estimated glomerular filtration rate (eGFR) (r = -0.503, p < 0.001), systolic
      blood pressure (r = -0.246, p = 0.034), and pulse pressure (r = -0.295, p =
      0.010). In contrast, serum creatinine correlated only with eGFR (r = -0.755, p <
      0.001) and eGFR correlated only with age (r = -0.339, p = 0.001) and not with the
      other clinical parameters, whereas cystatin C also correlated with log natural
      (ln) IL-6 (r = -0.247, p = 0.033) and ln TNF-alpha (r = -0.405, p < 0.001) but
      not with CRP (r = -0.188, p = 0.108). In contrast, plasma creatinine and eGFR did
      not correlate with any of these proinflammatory cytokines. Stepwise regression
      analysis showed that ln TNF-alpha, eGFR and pulse pressure were independent
      determinants of serum cystatin C concentration. CONCLUSION: This study showed
      that cystatin C is a marker of inflammation as well as renal function.

PMID- 20809112
TI  - Comparison of three methods for the estimation of the pituitary gland volume
      using magnetic resonance imaging: a stereological study.
AB  - Stereological techniques using point counting and planimetry have been used to
      estimate pituitary gland volume. However, many studies have estimated pituitary
      gland volume by the mathematical approach the elliptic formula. The objective of
      the current study was to determine pituitary gland volume using stereological
      methods and elliptic formula on magnetic resonance imaging (MRI). In this study,
      pituitary gland volumes were estimated in a total of 28 subjects (22 females, 6
      males,) who were free of any pituitary or neurological symptoms and signs. The
      mean +/- SD pituitary gland volumes for the point counting, planimetry and
      elliptic formulae groups were 582.14 +/- 140.16 mm3, 610.08 +/- 133.17 mm3, and
      432.82 +/- 147.38 mm3, respectively. The mean CE for the pituitary gland volume
      estimates derived from the point counting technique was 8.07%. No significant
      difference was found between point counting and planimetric methods for the
      pituitary gland volume (P > 0.05). In addition, there was a 26.14 and 29.71%
      underestimation of pituitary volume as measured by the elliptic formula compared
      to the point counting and planimetric techniques, respectively. From these
      results, it can be concluded that stereological techniques are unbiased,
      efficient and reliable methods and are ideally suitable for in vivo examination
      of MRI data for pituitary gland volume estimation. Hence, we suggest that
      estimating pituitary gland volume using MRI study and stereology may be
      clinically relevant for pituitary surgeons for the investigation of the structure
      and function of the pituitary gland.

PMID- 20809113
TI  - Demographic differences in incidence for pituitary adenoma.
AB  - Incidence estimates for pituitary adenomas vary widely, suggesting the effects of
      numerous risk factors or varying levels of tumor surveillance. We studied the
      epidemiology of pituitary adenomas using 2004-2007 data collected by 17
      Surveillance, Epidemiology, and End Results Programs in the United States (N =
      8,276). We observed that incidence rates generally increased with age and were
      higher in females in early life and higher in males in later life. Males are
      diagnosed with larger tumors on average than females. Diagnosis may be delayed
      for males, giving tumors a chance to grow larger before clinical detection. We
      also observed that American Blacks have higher incidence rates for pituitary
      adenomas compared with other ethnic groups. There are several potential
      explanations for this finding with some evidence that at least part of the effect
      may be due to differential diagnosis between races.

PMID- 20809114
TI  - Azathioprine as an alternative treatment in primary hypophysitis.
AB  - Primary hypophysitis (PH) is an unusual disorder characterized by inflammatory
      infiltration of the pituitary gland with various degree of pituitary dysfunction.
      Glucocorticoids are the treatment of choice in the majority of patients. Still,
      in patients with poor response in glucocorticoids or when their administration is
      accompanied with serious side effects, the use of alternative agents should be
      considered; up to now, data on other therapeutic approaches remains scant mainly
      due to the rarity of the disease. Among them, the immunosuppressant azathioprine
      could represent an effective and safe alternative. In this article, we present
      our clinical experience of two cases with PH successfully treated with
      azathioprine following serious side effects after initial treatment with
      glucocorticoids and provide a brief review of the existing literature.

PMID- 20809115
TI  - Outcome of renal transplant in patients with abnormal urinary tract.
AB  - PURPOSE: To determine whether surgical procedures of the lower urinary tract in
      patients with uropathies affect evolution of the graft in renal transplantation.
      METHODS: 156 kidney transplantations were performed in 150 patients with end
      stage renal failure due to urologic disorders. The patients were classified into
      three groups: A, patients who did not require surgery in the lower urinary tract;
      B, required surgery and preserved adequate bladder function, and C, required
      surgery due to vesical dysfunction. RESULTS: Graft survival rates at 1 year were
      93.38% in group A, 95.45% in group B and 93% in group C. Rates at 5 years post
      transplantation were 82.45, 79.85 and 86.58% for each group, respectively (not
      significant). Complications were vesicoureteral stenosis: 2 in group A, 3 in B
      and 1 in C; vesicoureteral reflux: 1 in group A, 1 in B and 10 in C; distal
      ureteral necrosis: 2 cases in group A, 2 in B and 1 in C; upper urinary tract
      infection: 12, 23.1 and 42.2% in each group, respectively. CONCLUSION: Children
      with reconstructed urinary tract may be good candidates for kidney
      transplantation despite the higher frequency of urinary infections. Thus, careful
      and strict post-surgical urologic follow-up is mandatory.

PMID- 20809117
TI  - Expression patterns of microRNAs are altered in hypoxic human neuroblastoma
      cells.
AB  - BACKGROUND/PURPOSE: There was a report that microRNA (miRNA) controls multiple
      genes. In addition, there are some reports that the presence of neoplastic cells
      that are hypoxic because of rapid tumor development is related to prognosis. As a
      step toward identifying the role of miRNA in hypoxic tumor cells, the present
      study was designed to determine which miRNAs have increased expression and which
      have decreased expression in hypoxic neuroblastoma cells. METHODS: For this
      study, we used seven neuroblastoma cell lines. In four with MYCN was amplified;
      in the other three MYCN was non-amplified. Neuroblastoma cells were cultured
      under hypoxic conditions. The expression levels of 662 kinds of miRNA in the
      hypoxic cells were quantified by gene array. RESULTS: We found that the
      expression of 85 kinds of miRNA was increased. Expression of six of these mRNAs
      was increased in two or more cell lines. Hsa-miR-143, -145, and -210 were each
      expressed in four of the seven cell lines. In addition, expression of 48 kinds of
      miRNA was decreased. Expression of five was decreased in two cell lines. There
      was no relation between the expression of miRNA and the amplification of MYCN.
      CONCLUSION: Our results thus suggest a possible causal relation between these
      three miRNAs and the malignancy of neuroblastoma in hypoxic conditions.

PMID- 20809118
TI  - Hydrocolonic sonography: a helpful diagnostic tool to implement effective bowel
      management.
AB  - Fecal incontinence is a serious problem that may lead to social segregation and
      psychological problems. Patients with anorectal malformations frequently suffer
      from fecal incontinence even with an excellent anatomic repair. In these
      patients, an effective management program with enemas can improve their quality
      of life. We want to present our experience with hydrocolonic sonography as a
      diagnostic tool to predict the type and volume of enema needed to initiate an
      effective bowel management. Patients who presented with soiling regardless of the
      type of anomaly were included in the study. Thirty patients aged 4-18 were
      evaluated. The diagnostic program comprised a careful clinical history, physical
      examination, exact classification of the malformation, evaluation for associated
      defects, and stool protocol. Twenty patients suffered from true fecal
      incontinence and were included in a bowel management program. These patients
      received oral polyethyleneglycol to evacuate stool impaction. Bowel management
      was initiated with the help of hydrosonography to evaluate bowel motility. The
      volume of the enema was determined according to the amount of fluid that was
      needed to fill the colon to the cecum. Twenty patients were investigated with the
      help of hydrocolonic sonography. Eighteen patients were free of symptoms of
      soiling after 3 days of hospital treatment and remained free of symptoms 6 months
      and 1 year later at reevaluation. Two patients did not follow the therapeutic
      regime and, therefore, did not show an improved condition concerning soiling in
      the long run. Hydrocolonic sonography is a helpful diagnostic tool to assess
      colonic volume and motility to predict the type and volume of enema needed for an
      effective bowel management.

PMID- 20809116
TI  - Clinical risk factors for gastroschisis and omphalocele in humans: a review of
      the literature.
AB  - Gastroschisis and omphalocele are usually considered together since they are both
      congenital abdominal wall defects, and yet their anatomy, embryogenesis, and
      clinical presentation and problems are quite different. In addition, it appears
      that the risk factors for their occurrence differ. Etiologic factors contributing
      to the development of these defects are unknown. To investigate this we have
      reviewed reports of risk factors for each anomaly and report them here. We
      conducted a literature search using PubMed (http://www.ncbi.nlm.nih.gov/pubmed/)
      for risk factors implicated in the development of gastroschisis and omphalocele.
      The data reviewed here from clinical studies in the literature, closely parallels
      the data in animal studies which we reported earlier. There is little evidence
      for a genetic cause in the development of gastroschisis and much evidence
      supporting the possibility that environmental teratogens are important
      contributors to the development of this defect. On the other hand, in the case of
      omphalocele, there was little evidence for environmental factors and substantial
      data indicating that genetic or familial factors may play an important role.

PMID- 20809119
TI  - Cell cycle and apoptosis regulatory protein (CARP)-1 is a novel, adriamycin
      inducible, diffuse large B-cell lymphoma (DLBL) growth suppressor.
AB  - Diffuse large B-cell lymphoma (DLCL) accounts for 30-40% of adult non-Hodgkin's
      Lymphoma (NHL). Current anti-NHL therapies often target cellular growth
      suppression pathways and include R-CHOP (cyclophosphamide, adriamycin,
      vincristine, and prednisone plus monoclonal anti-CD20 antibody rituximab).
      However, since many patients relapse, resistant cells to these therapies remain a
      significant problem and necessitate development of new intervention strategies.
      Cell cycle and apoptosis regulatory protein (CARP)-1 functions in a biphasic
      manner to regulate growth factor as well as chemotherapy (adriamycin, etoposide,
      or iressa)-dependent signaling. PURPOSE: To determine whether CARP-1 is a novel
      suppressor of lymphoma growth. METHODS: Flow cytometric analyses coupled with
      Western immunoblotting, cell growth, apoptosis, and immunocytochemistry
      methodologies were utilized to determine CARP-1-dependent lymphoma growth
      inhibition in vitro and in vivo. RESULTS: CARP-1 expression correlated with
      activated caspase-3 and inversely correlated with activated Akt in DLCL. Exposure
      to adriamycin stimulated CARP-1 expression and inhibited growth of Raji cells,
      but not CHOP-resistant WSU-DLCL2 cells. Expression of wild-type CARP-1 or its
      apoptosis-inducing mutants inhibited growth of Raji as well as CHOP-resistant WSU
      DLCL2 cells, in part by activating caspase-9 and apoptosis. Since CARP-1 harbors
      multiple, apoptosis-promoting subdomains, we investigated whether epigenetic
      compensation of CARP-1 function by intracellular delivery of trans-activator of
      transcription (TAT) domain-tagged CARP-1 peptide(s) will inhibit lymphoma growth.
      Treatments with TAT-tagged CARP-1 peptides suppressed growth of the Raji and WSU
      DLCL2 cells by stimulating apoptosis. TAT-CARP-1 (1-198) as well as (896-1150)
      peptides also suppressed growth of WSU-DLCL2 cell-derived tumor xenografts in
      SCID mice, while administration of TAT-CARP-1 (1-198) also inhibited growth of
      WSU-FSCCL cell-derived ascites and prolonged host survival. CONCLUSION: CARP-1 is
      a suppressor of NHL growth and could be exploited for targeting the resistant
      DLCL.

PMID- 20809121
TI  - Corticorelin acetate, a synthetic corticotropin-releasing factor with preclinical
      antitumor activity, alone and with bevacizumab, against human solid tumor models.
AB  - PURPOSE: Corticorelin acetate (CrA) is a synthetic form of corticotropin
      releasing factor undergoing clinical trials in the treatment of peritumoral brain
      edema (PBE). We sought to investigate preclinically its potential as an antitumor
      agent against human solid tumors and to assess its ability to enhance the
      therapeutic activity of bevacizumab (BEV) in these same models. METHODS: The in
      vivo efficacy of CrA as a single agent and in combination with the antiangiogenic
      agent, BEV, was examined in two preclinical human tumor models, the MX-1 breast
      and Colo-205 colon carcinomas. These models were selected based on their known
      sensitivity to BEV and were tumor types in which BEV has been approved for
      clinical use. The corneal micropocket assay was also performed to assess the
      antiangiogenic activity of CrA relative to BEV. The exposure level of CrA in the
      mouse using a typical preclinical regimen was measured so as to compare it to
      reported clinical exposure levels. RESULTS: CrA was active as a single agent in
      the MX-1 breast carcinoma, but did not exhibit statistically significant activity
      as a single agent in the Colo-205 colon carcinoma under the doses and schedules
      used in the study. When BEV, which was active or near active in both the MX-1 and
      Colo-205 models, was administered concomitantly with CrA, therapeutic outcomes
      were observed that were significantly better than those obtained using either
      monotherapy. These therapeutic potentiations using CrA plus BEV were obtained in
      the absence of any observable increase in toxicities. CrA was active in the
      corneal micropocket assay, producing a substantial (>70%) inhibition of
      neovascularization. A representative CrA regimen in mice produced an exposure
      within eightfold of human exposure determined at one-half the current clinical
      dose. CONCLUSIONS: The application of CrA for the treatment of PBE likely
      involves its activity as an antiangiogenic agent, which may be one possible
      mechanism to explain its observed preclinical antitumor activity. That activity,
      as well as its ability to provide an enhanced therapeutic outcome when given in
      conjunction with BEV in the absence of increased toxicity, supports the use of
      CrA clinically as other than a replacement therapy for dexamethasone in PBE.

PMID- 20809120
TI  - Uncoupling protein downregulation in doxorubicin-induced heart failure improves
      mitochondrial coupling but increases reactive oxygen species generation.
AB  - PURPOSE: Doxorubicin-based chemotherapy is limited by the development of dose
      dependent left ventricular dysfunction and congestive heart failure caused by
      reactive oxygen species (ROS). Uncoupling proteins (UCP) can inhibit
      mitochondrial ROS production as well as decrease myocyte damage from exogenous
      ROS. Prior studies have shown that cardiac UCP2 and UCP3 mRNA expression is
      decreased with acute doxorubicin treatment. However, the expression of UCP
      protein in hearts with doxorubicin cardiotoxicity and the resultant changes in
      mitochondrial function and oxidant stress have not been determined. METHODS:
      Heart failure was induced in Sprague-Dawley rats with intraperitoneal injections
      of doxorubicin (2 mg/kg t.i.w., total dose: 18 mg/kg). Mitochondria were isolated
      from mice receiving doxorubicin or saline injections for determination of UCP2
      and UCP3 expression. In addition, mitochondrial respiration, ATP synthesis and
      ROS production were determined. RESULTS: Doxorubicin-induced heart failure was
      associated with significant decreases in UCP2 and UCP3 protein expression
      compared with nonfailing hearts (P < 0.05). While the rates of state 3 and state
      4 respiration and ATP synthesis were lower in mitochondria isolated from failing
      hearts, the respiratory control ratio was 15% higher (P < 0.05), and the ratio of
      ATP production to oxygen consumption was 25% higher (P < 0.05) in mitochondria
      from failing hearts, indicating greater coupling between citric acid cycle flux
      and mitochondrial ATP synthesis. However, the decrease in UCP expression was
      associated with 50% greater mitochondrial ROS generation (P < 0.05). CONCLUSIONS:
      Downregulation of myocardial UCP2 and UCP3 in the setting of doxorubicin-induced
      heart failure is associated with improved efficiency of ATP synthesis, which
      might compensate for abnormal energy metabolism. However, this beneficial effect
      is counterbalanced by greater oxidant stress.

PMID- 20809122
TI  - Picoplatin overcomes resistance to cell toxicity in small-cell lung cancer cells
      previously treated with cisplatin and carboplatin.
AB  - PURPOSE: Picoplatin is a new generation platinum designed to overcome platinum
      resistance. The goal of this study was to assess picoplatin anti-tumor activity
      and measure various cellular parameters in small-cell lung cancer (SCLC) cells
      resistant to cell killing by cisplatin and carboplatin. METHODS: We developed
      several platinum-resistant SCLC cell lines to evaluate picoplatin activity and
      drug resistance mechanisms in vitro. Drug cytotoxicity was measured by MTS assay.
      Total cellular platinum accumulation was measured by inductively coupled plasma
      mass spectrometry (ICP-MS). Whole genome gene expression profiling was carried
      out by microarray analysis. RESULTS: Picoplatin retained significant cytotoxic
      activity in platinum-resistant SCLC lines compared to cisplatin and carboplatin.
      Cellular picoplatin accumulation in platinum-resistant and parental cells was
      high relative to levels of cellular platinum found in the same cell lines after
      cisplatin or carboplatin treatment. Gene expression analyses revealed substantial
      differences in gene expression and highlighted specific annotation clusters in
      carboplatin-resistant cells. In addition, a similar gene expression pattern was
      observed in picoplatin-treated carboplatin-resistant and parental cells.
      CONCLUSIONS: Our study demonstrates that picoplatin can overcome carboplatin and
      cisplatin resistance. The results suggest decreased platinum accumulation as a
      potential mechanism of platinum resistance in SCLC cells, provide candidate
      markers (e.g. several genes in the Hox, glutathione biosynthetic process, and
      MAGE families) that may serve as signatures for platinum resistance, support
      distinct effects of picoplatin on SCLC cells compared to other platinums, and
      provide a rationale to develop picoplatin for the treatment of recurrent SCLC
      following initial therapy with cisplatin or carboplatin.

PMID- 20809123
TI  - Feasibility study of adjuvant chemotherapy with S-1 plus cisplatin for gastric
      cancer.
AB  - PURPOSE: To evaluate the feasibility of S-1 plus cisplatin as adjuvant
      chemotherapy for stage III gastric cancer after curative resection. METHODS:
      Japanese patients with stage III gastric cancer who underwent gastrectomy with D2
      lymph node resection were enrolled. Treatment consisted of 3 cycles of S-1 (80
      mg/m(2)/day, b.i.d.) for 21 days followed by a 14-day rest, and cisplatin (60
      mg/m(2) iv) on day 8. After that, S-1 monotherapy was given on days 1-28 every 6
      weeks until 1-year postsurgery. After protocol amendment, the first chemotherapy
      cycle consisted of S-1 monotherapy; cisplatin was added to cycles 2, 3, and 4,
      followed by S-1 monotherapy up to 1-year postsurgery. The primary endpoint was
      the completion rate of three cycles of S-1 plus cisplatin. RESULTS: A total of 63
      enrolled patients have been evaluated. Grade 3/4 toxicities included neutropenia
      (40%), anorexia (28%), and febrile neutropenia (4%) before protocol amendment (n
      = 25), and neutropenia (37%), anorexia (8%), and febrile neutropenia (3%) after
      amendment implementation (n = 38). Excluding ineligible cases, treatment
      completion rates were 57% (12/21) before and 81% (30/37) after the protocol
      amendment. CONCLUSIONS: The amended S-1 plus cisplatin is more feasible than the
      original protocol because of early dose reduction of S-1 prior to cisplatin
      addition and greater recovery time from surgery prior to cisplatin. This
      treatment should be considered as a feasible experimental arm for the next
      postoperative adjuvant phase III trial.

PMID- 20809124
TI  - Comorbidity of anxiety and conduct problems in children: implications for
      clinical research and practice.
AB  - Given the relative lack of research on the comorbidity of anxiety disorders (ADs)
      and conduct problems (oppositional defiant disorder, conduct disorder) in youth,
      we examine this comorbidity from both basic and applied perspectives. First, we
      review the concept of comorbidity and provide a framework for understanding
      issues pertaining to comorbidity. Second, we examine the comorbidity of ADs and
      conduct problems in both epidemiological and clinical studies. Third, we explore
      the artifactual and substantive reasons for the comorbidity of these disorders.
      Finally, we discuss the implications of comorbidity for assessment and treatment
      and provide recommendations for future directions in clinical research and
      practice.

PMID- 20809125
TI  - Cardioprotective effect of zinc requires ErbB2 and Akt during
      hypoxia/reoxygenation.
AB  - Recent literature suggests that exogenous zinc can prevent ischemia reperfusion
      injury by activating phosphoinositide-3 kinase (PI3K)/Akt and by targeting the
      mitochondrial permeability transition pore (mPTP). It is known that ErbB2
      expression promotes association and activation of PI3-kinase/Akt, resulting in
      growth and survival of cardiac myocytes. In this study, we found that zinc
      induced ErbB2 protein expression and Akt activation are required for preventing
      reperfusion injury. Neonatal rat cardiac myocytes subjected to 8 h of hypoxia,
      followed by 16 h of reoxygenation induced cardiomyocyte apoptosis, as assessed by
      increased caspase-3 activity, annexin V staining and lowered MTT reduction and
      ATP levels. However, addition of zinc-pyrithione (ZPT) before onset of
      reoxygenation effectively lowered the apoptotic indices and restored the ATP
      levels. ZPT induced a significant increase in ErbB2 protein expression and Akt
      activation. Pretreatment with Hsp 90 inhibitor, geldanamycin or PI3-kinase
      inhibitor, wortmannin prevented the increase in ATP levels and abrogated the
      protective effect of zinc-pyrithione. Taken together, these data suggest that
      zinc prevents reperfusion injury by modulating the ErbB2 protein expression and
      Akt activation.

PMID- 20809126
TI  - Computed tomography for the detection of free-floating thrombi in the right heart
      in acute pulmonary embolism.
AB  - OBJECTIVES: The aim of this study was to assess the prevalence of free-floating
      thrombi in the right heart (FFT) and the accuracy of computed tomography (CT) for
      their detection in pulmonary embolism (PE). METHODS: We studied 340 consecutive
      patients presenting with PE. All patients underwent CT and echocardiography.
      RESULTS: The prevalence of FFT was 3.5% in the global population of PE and 22% in
      high-risk PE. Dyspnoea, cardiogenic shock, cardiac arrest and tachycardia were
      more frequently found in patients with FFT (p = 0.04, p < 0.0001, p = 0.0003 and
      p = 0.01, respectively). Sensitivity and specificity of CT for the detection of
      FFT were 100% (95% confidence interval: 74%-100%) and 97% (95%-99%), whereas
      positive and negative predictive values were 57% (34%-78%) and 100% (99%-100%).
      Among patients with FFT, right ventricular dilation was always detected by CT,
      whereas no right ventricular dilation was found among patients with a false
      diagnosis of FFT performed by CT (p < 0.0001). CONCLUSION: Prevalence of FFT is
      3.5% and differs according to the clinical presentation. Detection of FFT by CT
      is feasible and should lead to echocardiography being promptly performed for the
      confirmation of FFT.

PMID- 20809127
TI  - Contrast-enhanced magnetic resonance angiography (MRA): evaluation of three
      different contrast agents at two different doses (0.05 and 0.1 mmol/kg) in pigs
      at 1.5 Tesla.
AB  - OBJECTIVE: To compare the image quality of contrast-enhanced magnetic resonance
      angiography (CE-MRA) of the supra-aortic vessels at 0.05 mmol/kg bw and 0.1
      mmol/kg bw, between gadobutrol, Gd-DTPA and Gd-BOPTA quantitatively and
      qualitatively a total of eight pigs were evaluated intraindividually at 1.5 T.
      METHODS: Each pig was examined using 0.1 mmol/kg gadobutrol, Gd-DTPA and Gd-BOPTA
      on day one and 0.05 mmol/kg on day two. MRA datasets for the carotid artery and
      the infraorbital artery were qualitatively assessed regarding overall image
      quality on an ordinal four-point scale (4-excellent, 1-non-diagnostic). The
      signal-to noise-ratio (SNR) was measured. RESULTS: The qualitative assessment of
      the carotid artery showed a higher median image quality for the 0.1 mmol dose
      than for the 0.05 mmol dose for all three compounds. No difference was found for
      the infraorbital artery. Mean SNR of Gd-BOPTA, Gd-DTPA, gadobutrol at 0.05
      mmol/kg were 36.0 +/- 13.4/37.9 +/- 16.3/43.7 +/- 0.4 and at 0.1 mmol/kg they
      were 50.1 +/- 12.4/46.6 +/- 6.5 / 54.6 +/- 10.2. Gd-BOPTA 0.05 revealed a
      significantly lower SNR than all other agents at normal dose. CONCLUSIONS: Full
      dose gadolinium MRA results in higher image quality and significantly higher SNR
      compared with the half dose. Gadobutrol and Gd-BOPTA have similar enhancement
      properties at full dose but at half dose, gadobutrol appears superior.

PMID- 20809128
TI  - Deterioration of abstract reasoning ability in mild cognitive impairment and
      Alzheimer's disease: correlation with regional grey matter volume loss revealed
      by diffeomorphic anatomical registration through exponentiated lie algebra
      analysis.
AB  - OBJECTIVE: To determine which brain regions are relevant to deterioration in
      abstract reasoning as measured by Raven's Colored Progressive Matrices (CPM) in
      the context of dementia. METHODS: MR images of 37 consecutive patients including
      19 with Alzheimer's disease (AD) and 18 with amnestic mild cognitive impairment
      (aMCI) were retrospectively analyzed. All patients were administered the CPM.
      Regional grey matter (GM) volume was evaluated according to the regimens of voxel
      based morphometry, during which a non-linear registration algorithm called
      Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra was
      employed. Multiple regression analyses were used to map the regions where GM
      volumes were correlated with CPM scores. RESULTS: The strongest correlation with
      CPM scores was seen in the left middle frontal gyrus while a region with the
      largest volume was identified in the left superior temporal gyrus. Significant
      correlations were seen in 14 additional regions in the bilateral cerebral
      hemispheres and right cerebellum. CONCLUSION: Deterioration of abstract reasoning
      ability in AD and aMCI measured by CPM is related to GM loss in multiple regions,
      which is in close agreement with the results of previous activation studies.

PMID- 20809129
TI  - Diagnostic accuracy and clinical impact of imaging-guided needle biopsy of renal
      masses. Retrospective analysis on 150 cases.
AB  - OBJECTIVE: To review our method of perform needle biopsies of renal masses.
      METHODS: We analysed 150 consecutive imaging-guided percutaneous biopsies. The
      pathological diagnosis was verified on clinical outcome in 129 cases (40 surgical
      resection, 53 thermal ablation, two medical treatment and 34 watchful waiting).
      Twenty-six patients underwent fine-needle aspiration biopsy (FNAB), 45 core
      needle biopsy (CB) and 58 FNAB + CB. After review by two expert pathologists,
      cumulative accuracy of all FNAB (84) and all CB (103) was calculated. The rate of
      complications and mass management other than surgery was estimated. RESULTS: The
      final diagnosis was malignancy in 97 cases (benign mass in 32). FNAB correctly
      diagnosed 64/84 masses (76.2%), CB 96/103 (93.2%). Of 58 masses submitted for
      both FNAB and CB, CB provided a 22.5% accuracy improvement. Major and minor
      complications occurred in 0% and 5.3%. Renal biopsy altered clinical management
      in 89/129 cases (68.9%), in terms of choosing therapeutic options other than
      surgery. CONCLUSION: CB is more accurate than FNAB and should be preferred in
      renal mass biopsy. FNAB may precede CB when an expert pathologist can immediately
      evaluate the samples. Renal biopsy influences renal mass management.

PMID- 20809130
TI  - Technical refinements of bile duct division in living donor liver surgery.
AB  - BACKGROUND/PURPOSE: In spite of the great risk involved, the donor bile duct
      division procedure has not been thoroughly addressed in the literature. The
      purpose of this study is to show the appropriate approach to bile duct division
      in living donor hepatectomy. METHODS: Of 87 living donor liver surgeries, we
      performed bile duct division by marking the cutting point using a small vascular
      clip under ordinary cholangiography in the first 37 patients, while the current
      procedure was used in 50 patients by encircling the cutting point using a
      radiopaque marker filament under real-time C-arm cholangiography. RESULTS:
      Regarding the procurement of the 51 right lobe grafts, the incidence of multiple
      bile ducts in the graft was significantly reduced by our novel procedure [20/28
      (71%) vs. 7/23 (30%), P < 0.01, Fisher's test]. Overall, there were no biliary
      strictures after surgery in any of the donors, with a median follow-up period of
      43 months (range 8-136). CONCLUSIONS: Our procedure of bile duct division in
      living liver donor surgery enabled us to avoid the biliary stricture while
      cutting the bile duct of the donor with great accuracy.

PMID- 20809132
TI  - Biophysical characterization of recombinant HIV-1 subtype C virus infectivity
      factor.
AB  - HIV-1 virus infectivity factor (Vif) is one of the four accessory proteins that
      are characteristic of primate lentiviruses and critically required for the
      infection of host cells. Vif plays a key role in replication and transmission of
      the virus in non-permissive cells, such as primary T cells and macrophages. Using
      co-precipitation and co-fractionation techniques, evidence has been provided that
      Vif interacts with a variety of host proteins, such as the cytidine deaminases
      APOBEC3G and 3F, the Cullin5/EloBC ubiquitin-ligase complex, Fyn and Hck tyrosine
      kinases, as well as with viral components, such as the immature Gag precursor and
      viral RNA. We report on the expression, purification and molecular
      characterization of a folded recombinant subtype C Vif. Vif was expressed in E.
      coli with a C-terminal hexahistidine tag and purified by nickel affinity
      chromatography. We obtained approximately 5 mg protein per liter of bacterial
      culture, with a purity >95%. The expected molecular mass of 23.7 kDa was
      confirmed by mass spectrometry. Although dynamic light scattering and small angle
      X-ray scattering measurements revealed the presence of high molecular weight
      aggregates in the protein preparation, circular dichroism analysis showed that
      the protein contains mainly folded beta-sheet elements and exhibits remarkable
      thermal stability (T (m) > 95 degrees C). Recombinant Vif may be used as a tool
      to study its biological functions and tertiary structure, as well as for the
      development of diagnostic, therapeutic and preventive strategies for HIV-1
      infections.

PMID- 20809131
TI  - Small molecule inhibitors of DNA repair nuclease activities of APE1.
AB  - APE1 is a multifunctional protein that possesses several nuclease activities,
      including the ability to incise at apurinic/apyrimidinic (AP) sites in DNA or
      RNA, to excise 3'-blocking termini from DNA ends, and to cleave at certain
      oxidized base lesions in DNA. Pre-clinical and clinical data indicate a role for
      APE1 in the pathogenesis of cancer and in resistance to DNA-interactive drugs,
      particularly monofunctional alkylators and antimetabolites. In an effort to
      improve the efficacy of therapeutic compounds, such as temozolomide, groups have
      begun to develop high-throughput screening assays and to identify small molecule
      inhibitors against APE1 repair nuclease activities. It is envisioned that such
      inhibitors will be used in combinatorial treatment paradigms to enhance the
      efficacy of DNA-interactive drugs that introduce relevant cytotoxic DNA lesions.
      In this review, we summarize the current state of the efforts to design potent
      and selective inhibitors against APE1 AP site incision activity.

PMID- 20809133
TI  - Effects of local tissue conductivity on spherical and realistic head models.
AB  - In this study, we consider different conductivity values based on tissue location
      in a human head model. We implement local conductivity (LC) to compute head
      surface potentials in three-, four-layered spherical and realistic head models
      using finite element method (FEM). Implementing LC for all head models, we obtain
      significant scalp potential variations in the term of relative difference
      measurement (RDM) and magnification (MAG) values with a maximum of 2.03+/-1.81
      and 8.27+/-6.36, respectively. We also investigate the effects of conductivity
      variations (CVs) of head tissue layer on scalp potentials and find a maximum of
      2.15+/-1.93 RDM and 8.57+/-6.61 MAG values. Our study concludes that it is
      important to assign LC to each tissue and it is also important to assign
      appropriate conductivity value in the construction of a head model for achieving
      accurate scalp potentials.

PMID- 20809135
TI  - Luminescence enhancement from silica-coated gold nanoparticle agglomerates
      following multi-photon excitation.
AB  - Multi-photon absorption induced luminescence (MAIL) from bare gold nanoparticles,
      silica-coated particles, as well as silica-coated agglomerated gold nanoparticles
      suspended in aqueous solution was studied by using time-resolved and steady-state
      luminescence spectroscopy. The nanoparticles were excited by femtosecond pulses
      of wavelengths ranging from 630 nm to 900 nm. The luminescence from the particles
      exhibits a broad spectrum in the UV and VIS region. The time-resolved
      measurements indicate a luminescence lifetime of a few ps, limited by the
      response of the experimental system. The studied dependence of the MAIL
      efficiency on the excitation wavelength showed that the luminescence from silica
      coated agglomerates was enhanced over the whole range of excitation wavelengths,
      when compared to the luminescence from individual gold nanoparticles. The
      agglomerates show an almost excitation wavelength independent efficiency of the
      MAIL, while for individual nanoparticles a rapid decrease of the MAIL efficiency
      was observed with increasing excitation wavelength. The observed enhancement of
      the MAIL from the agglomerated nanostructures can be attributed to the presence
      of localized surface plasmon resonances in the spectral region corresponding to
      the excitation wavelengths. The high MAIL efficiency from the agglomerated
      nanoparticle structures in the near-infrared could be an advantage in the
      expanding field of luminescence-based-imaging, as well as in biosensor
      technology.

PMID- 20809134
TI  - Expression of heat shock protein-coding genes associated with anhydrobiosis in an
      African chironomid Polypedilum vanderplanki.
AB  - In order to survive in extreme environments, organisms need to develop special
      adaptations both on physiological and molecular levels. The sleeping chironomid
      Polypedilum vanderplanki, inhabiting temporary water pools in semi-arid regions
      of Africa, is the only insect to have evolutionarily acquired the ability to
      withstand prolonged complete desiccation at larval stage, entering a state called
      anhydrobiosis. Even after years in a dry state, larvae are able to revive within
      a short period of time, completely restoring metabolism. Because of the possible
      involvement of stress proteins in the preservation of biomolecules during the
      anhydrobiosis of the sleeping chironomid, we have analyzed the expression of
      genes encoding six heat shock proteins (Pv-hsp90, Pv-hsp70, Pv-hsc70, Pv-hsp60,
      Pv-hsp20, and Pv-p23) and one heat shock factor (Pv-hsf1) in dehydrating,
      rehydrating, and heat-shocked larvae. All examined genes were significantly up
      regulated in the larvae upon dehydration and several patterns of expression were
      detected. Gene transcript of Pv-hsf1 was up-regulated within 8 h of desiccation,
      followed by large shock proteins expression reaching peak at 24-48 h of
      desiccation. Heat-shock-responsive Pv-hsp70 and Pv-hsp60 showed a two-peak
      expression: in dehydrating and rehydrating larvae. Both small alpha-crystallin
      heat shock proteins (sHSP) transcripts were accumulated in the desiccated larvae,
      but showed different expression profiles. Both sHSP-coding genes were found to be
      heat-inducible, and Pv-hsp20 was up-regulated in the larvae at the early stage of
      desiccation. In contrast, expression of the second transcript, corresponding to
      Pv-p23, was limited to the late stages of desiccation, suggesting possible
      involvement of this protein in the glass-state formation in anhydrobiotic larvae.
      We discuss possible roles of proteins encoded by these stress genes during the
      different stages of anhydrobiosis in P. vanderplanki.

PMID- 20809136
TI  - Mono and trimethine cyanines Cyan 40 and Cyan 2 as probes for highly selective
      fluorescent detection of non-canonical DNA structures.
AB  - Two of earlier reported dsDNA sensitive cyanine dyes-monomethine Cyan 40 and meso
      substituted trimethine Cyan 2 were studied for their ability to interact with non
      canonical DNA conformations. These dyes were characterized by spectral
      luminescent methods in the presence of G-quadruplex, triplex and dsDNA motifs. We
      have demonstrated that Cyan 2 binds strongly and preferentially to triple- and
      quadruple-stranded DNA forms that results in a strong enhancement of the dye
      fluorescence, as compared to dsDNA, while Cyan 40 form fluorescent complexes
      preferentially only with the triplex form. Highly fluorescent complexes of Cyan 2
      with DNA triplexes and G-quadruplexes and Cyan 40 with DNA triplexes are very
      stable and do not dissociate during gel electrophoresis, leading to preferential
      staining of the above DNA forms in gels. The data presented point to the
      intercalation mechanism of the Cyan 2 binding to G4-DNA, while the complexes of
      Cyan 40 and Cyan 2 with triplex DNA are believed to be formed via groove binding
      mode. The Cyan dyes can provide a highly sensitive method for detection and
      quantification of non-canonical structures in genome.

PMID- 20809137
TI  - A novel Dmrt gene is specifically expressed in the testis of Chinese mitten crab,
      Eriocheir sinensis.
AB  - Dmrt is a family of genes related to the sexual regulators Doublesex of
      Drosophila melanogaster and Mab-3 of Caenorhabditis elegans. Dmrt genes are
      widely conserved and known for their involvement in sex determination and
      differentiation across phyla. In this study, we report here the identification of
      a novel Dmrt gene, named EsDmrt-like, from Chinese mitten crab Eriocheir
      sinensis. EsDmrt-like encodes a protein of 236 amino acids without intron. The
      protein contains a conserved DNA-binding DM domain that is characteristic of Dmrt
      genes. The DM domain shares 98% identity with that of Drosophila Dmrt99B and
      vertebrate Dmrt5, but outside the DM domain, there is little homology in sequence
      and no other conserved domain such as DMA specific to the Dmrt99B and Dmrt3-5.
      Interestingly, the expression pattern of EsDmrt-like is quite similar with that
      of vertebrate Dmrt1. Reverse transcription-polymerase chain reaction showed that
      EsDmrt-like transcripts were detectable only in testis with much higher
      expression at immature stage. In situ hybridization to gonad sections indicated
      that the EsDmrt-like mRNA was exclusively localized in Sertoli cells around the
      periphery of seminiferous tubules and developing germ cells including
      spermatogonium, spermatocyte, and spermatid, but absent in spermatozoa. This
      finding strongly suggests an essential role for EsDmrt-like in the male
      testicular development/differentiation of the crab.

PMID- 20809138
TI  - Imaging of a rat osteoarthritis model using (18)F-fluoride positron emission
      tomography.
AB  - OBJECTIVE: Currently, conventional radiography is the standard method for the
      diagnosis and evaluation of the severity of osteoarthritis (OA), but it takes a
      couple of years to detect cartilage loss. Magnetic resonance imaging can
      delineate articular cartilage and accurately assess cartilage volume and
      thickness, but its reliability for very early diagnosis of OA is still
      controversial. The purpose of this study was to confirm the potential of (18)F
      fluoride PET for the early diagnosis of OA by using a surgically induced rat OA
      model. METHODS: Seventeen 16-week-old male Sprague-Dawley rats underwent anterior
      cruciate ligament transection (ACLT) in the right knee to induce OA. The left
      knee underwent sham operation. At 2, 4, and 8 weeks after operation, the rats
      were injected with 2.5 MBq/kg of (18)F-fluoride, and 30 min after injection, each
      rat was killed and the bilateral knees were resected. The femur and tibia were
      cut horizontally, approximately 2 mm from the joint surface excluding the growth
      plate, and were cut into the medial and lateral condyles. The patella was also
      resected and blood samples were collected. The radioactivity of each sample was
      measured by gamma counting. Assays for serum cartilage oligomeric matrix protein
      and serum C-telopeptide of type II collagen were performed. Histopathological
      grading was performed according to a modified Mankin's scoring system. Two rats
      underwent PET scans at 2, 4, and 8 weeks after operation. The rats were injected
      with 30 MBq of (18)F-fluoride, and 30 min after injection, bilateral knee images
      with a 30-min acquisition time were obtained with an animal PET system. RESULTS:
      The uptake of (18)F-fluoride was significantly higher in ACLT knees than sham
      operated knees in the medial femur and medial tibia at 2 weeks after operation.
      At 4 weeks after operation, the medial femur, medial tibia, and lateral tibia of
      OA knees showed significantly higher uptake of (18)F-fluoride compared with sham
      operated knees. At 8 weeks, all sections showed significant differences. The
      uptake of (18)F-fluoride significantly increased as time elapsed in all sections.
      Uptake showed a significant correlation with histological scores. CONCLUSION: Our
      results suggest that (18)F-fluoride is potentially useful for the early detection
      of osteoarthritic changes.

PMID- 20809139
TI  - Lymphoscintigraphy for sentinel lymph node mapping in Japanese patients with
      malignant skin neoplasms of the lower extremities: comparison with previously
      investigated Japanese lymphatic anatomy.
AB  - OBJECTIVES: Lymph nodes (LN) and lymphatic drainage were identified by
      lymphoscintigraphy using 99(m)Tc-phytate in order to map the sentinel lymph nodes
      (SLNs) in patients with malignant skin neoplasms of the lower extremities, and to
      compare the results with an atlas of Japanese lymphatic anatomy. METHODS:
      Sentinel lymphoscintigraphs of 18 patients with malignant skin neoplasms of the
      lower extremities (9 men, 9 women; age range 45-84 years, mean age 66 years) were
      analyzed retrospectively, and the LNs detected were identified as SLNs or
      secondary nodes. RESULTS: The patterns of lymphatic drainage were divided into
      three different categories: (1) initial drainage into inguinal LN without
      visualization of popliteal LNs (inguinal type), (2) initial drainage into
      popliteal LNs and then into intrapelvic LNs (popliteal type), and (3) initial
      drainage into both popliteal and inguinal LNs (inguinal and popliteal type). More
      than half of the cases were the inguinal and popliteal type, as both inguinal and
      popliteal LNs were identified as SLNs. In the cases in which the hallux and its
      surrounding area were injected, all were the inguinal type and popliteal LNs were
      not visualized. In one case, only dynamic images detected lymphatic drainage
      without visualization of popliteal LNs. In contrast to the previously published
      literature on Japanese lymphatic anatomy, SLN lymphatic drainage from the skin of
      the lower extremities was wide and overlapping in many areas. However, in
      agreement with currently accepted anatomy, only the great saphenous lymphatic
      vessel drained the skin of the hallux and its surrounding area. The present
      results suggest that it is important to confirm lymphatic drainage in order to
      identify SLNs in the lower extremities. CONCLUSIONS: The patterns of lymphatic
      drainage from the skin of the foot were divided into three different categories.
      In contrast to previously published Japanese lymphatic anatomy, lymphatic
      drainage from the skin of the lower extremities was wide and overlapping in many
      areas. However, only the great saphenous lymphatic vessel drained the skin of the
      hallux and its surrounding area in agreement with currently accepted Japanese
      lymphatic anatomy. It is important to confirm lymphatic drainage to identify SLNs
      in the lower extremities.

PMID- 20809140
TI  - Correlation between plasma and saliva adrenocortical hormones in response to
      submaximal exercise.
AB  - This study examined the relationships between plasma and saliva adrenocortical
      hormones in response to long-duration submaximal exercise. In nine healthy,
      physically active, female volunteers, blood and saliva samples were taken at rest
      and every 30 min during a 120-min cycling trial at 50-55% VO(2max) for cortisol
      and dehydroepiandrosterone (DHEA) analysis. Correlation analysis revealed a
      moderate but significant relationship between plasma and saliva cortisol (r =
      0.35, P < 0.02) and plasma and saliva DHEA (r = 0.47, P < 0.001) during the
      submaximal exercise. When expressed in percent of resting values, the
      correlations between the plasma and saliva concentrations were higher for both
      hormones during the exercise (cortisol: r = 0.72; DHEA: r = 0.68, P < 0.001). The
      results thus suggest that, even under prolonged exercise conditions, non-invasive
      saliva samples may offer a practical approach to assessing pituitary-adrenal
      function, especially when compared with individual basal values.

PMID- 20809141
TI  - Synergistic effects of amides from two piper species on generalist and specialist
      herbivores.
AB  - Plants use a diverse mix of defenses against herbivores, including multiple
      secondary metabolites, which often affect herbivores synergistically. Chemical
      defenses also can affect natural enemies of herbivores via limiting herbivore
      populations or by affecting herbivore resistance to parasitoids. In this study,
      we performed feeding experiments to examine the synergistic effects of imides and
      amides (hereafter "amides") from Piper cenocladum and P. imperiale on specialist
      (Eois nympha, Geometridae) and generalist (Spodoptera frugiperda, Noctuidae)
      lepidopteran larvae. Each Piper species has three unique amides, and in each
      experiment, larvae were fed diets containing different concentrations of single
      amides or combinations of the three. The amides from P. imperiale had negative
      synergistic effects on generalist survival and specialist pupal mass, but had no
      effect on specialist survival. Piper cenocladum amides also acted synergistically
      to increase mortality caused by parasitoids, and the direct negative effects of
      mixtures on parasitoid resistance and pupal mass were stronger than indirect
      effects via changes in growth rate and approximate digestibility. Our results are
      consistent with plant defense theory that predicts different effects of plant
      chemistry on generalist versus adapted specialist herbivores. The toxicity of
      Piper amide mixtures to generalist herbivores are standard bottom-up effects,
      while specialists experienced the top-down mediated effect of mixtures causing
      reduced parasitoid resistance and associated decreases in pupal mass.

PMID- 20809142
TI  - The influence of pine volatile compounds on the olfactory response by Neodiprion
      sertifer (Geoffroy) females.
AB  - Females of the pine sawfly Neodiprion sertifer (Hymenoptera Diprionidae) usually
      avoid Pinus pinea trees as host plants. In contrast, this sawfly species is
      highly attracted by P. sylvestris and P. nigra trees. Here, we investigated which
      pine volatiles might mediate this behavior by in situ sampling experiments and
      olfactometer laboratory tests. Volatiles emitted from P. pinea, P. sylvestris,
      and P. nigra foliage were sampled by solid-phase microextraction (SPME). Analysis
      of these volatiles by coupled gaschromatography/mass spectrometry revealed that
      the relative amounts of the compounds emitted by the three species were
      significantly different. A discriminant analysis showed that the amounts of
      limonene and myrcene significantly contributed to the species-specific volatile
      patterns. Pinus pinea emitted higher relative amounts of limonene than the other
      pine species. Pinus sylvestris emitted the highest relative amounts of myrcene.
      When testing the response of N. sertifer females to these pine terpenoids in an
      olfactometer bioassay, a low amount of limonene was attractive, while a repellent
      effect was evident when higher amounts were used. The sawfly females showed no
      significant olfactory response to myrcene. These data suggest that low relative
      amounts of limonene have a significant function in attracting N. sertifer
      females, while high amounts might contribute to avoidance of a tree.

PMID- 20809143
TI  - Male-produced sex pheromone of the cerambycid beetle Hedypathes betulinus:
      chemical identification and biological activity.
AB  - We identified, synthesized, determined the diel periodicity of release, and
      tested the bioactivity of components of the male-produced sex pheromone of
      Hedypathes betulinus (Coleoptera: Cerambycidae: Lamiinae). Gas chromatographic
      mass spectrometric analysis of headspace volatiles from adult beetles showed
      three male-specific compounds, which were identified as (E)-6,10-dimethyl-5,9
      undecadien-2-yl acetate (major component), (E)-6,10-dimethyl-5,9-undecadien-2-one
      (geranylacetone), and (E)-6,10-dimethyl-5,9-undecadien-2-ol. Release of these
      chemicals was dependent on time of the photoperiod and presence of the host
      plant. Pheromone release took place primarily during the photophase, with maximum
      release occurring between 4 and 6 hr after the onset of photophase. The amount of
      pheromone released by males was much greater when they were in the presence of
      their host plant than when they were not. In Y-tube olfactometer tests, a ternary
      mixture of the compounds was attractive to female beetles, although the
      individual compounds were not attractive by themselves. Addition of volatiles
      from the host plant greatly increased the attractiveness of the ternary pheromone
      mixture and of the major pheromone component alone.

PMID- 20809144
TI  - Host plant influences on iridoid glycoside sequestration of generalist and
      specialist caterpillars.
AB  - The effect of diet on sequestration of iridoid glycosides was examined in larvae
      of three lepidopteran species. Larvae were reared upon Plantago major, or P.
      lanceolata, or switched from one to the other in the penultimate instar. Junonia
      coenia is a specialist on iridoid glycoside-producing plants, whereas the
      arctiids, Spilosoma congrua and Estigmene acrea, are both polyphagous and eat
      iridoid-producing plants. All species sequestered iridoids. The specialist J.
      coenia sequestered from three to seven times the amounts sequestered by the two
      generalist species. Junonia coenia iridoid glycoside content depended on diet,
      and they sequestered from 5 to 15% dry weight iridoid glycosides. Estigmene acrea
      iridoid glycoside sequestration was relatively low, around 2% dry weight and did
      not vary with diet. Spilosoma congrua sequestration varied with diet and ranged
      from approximately 3 to 6% dry weight.

PMID- 20809145
TI  - Allelochemical effects of volatile compounds and organic extracts from Muscodor
      yucatanensis, a tropical endophytic fungus from Bursera simaruba.
AB  - Muscodor yucatanensis, an endophytic fungus, was isolated from the leaves of
      Bursera simaruba (Burseraceae) in a dry, semideciduous tropical forest in the
      Ecological Reserve El Eden, Quintana Roo, Mexico. We tested the mixture of
      volatile organic compounds (VOCs) produced by M. yucatanensis for allelochemical
      effects against other endophytic fungi, phytopathogenic fungi and fungoids, and
      plants. VOCs were lethal to Guignardia mangifera, Colletotrichum sp., Phomopsis
      sp., Alternaria solani, Rhizoctonia sp., Phytophthora capsici, and P. parasitica,
      but had no effect on Fusarium oxysporum, Xylaria sp., the endophytic isolate 120,
      or M. yucatanensis. VOCs inhibited root elongation in amaranth, tomato, and
      barnyard grass, particularly those produced during the first 15 days of fungal
      growth. VOCs were identified by gas chromatography/mass spectrometry and included
      compounds not previously reported from other Muscodor species and the previously
      reported compounds octane, 2-methyl butyl acetate, 2-pentyl furan, caryophyllene,
      and aromadendrene. We also evaluated organic extracts from the culture medium and
      mycelium of M. yucatanensis on the same endophytes, phytopathogens, and plants.
      In general, extracts inhibited plants more than endophytic or phytopathogens
      fungi. G. mangifera was the only organism that was significantly stimulated by
      both extracts regardless of concentration. Compounds in both organic extracts
      were identified by gas chromatography/mass spectrometry. We discuss the possible
      allelopathic role that metabolites of M. yucatanensis play in its ecological
      interactions with its host plant and other organisms.

PMID- 20809146
TI  - Defensive secretions in three species of polydesmids (Diplopoda, Polydesmida,
      Polydesmidae).
AB  - Nine compounds were detected in three different millipede species: Polydesmus
      complanatus (L.), Brachydesmus (Stylobrachydesmus) avalae Curcic & Makarov, and
      Brachydesmus (Stylobrachydesmus) dadayi Verhoeff. Benzaldehyde, benzyl alcohol,
      benzoylnitrile, benzyl methyl ketone, benzoic acid, benzyl ethyl ketone,
      mandelonitrile, and mandelonitrile benzoate were identified by GC-FID and GC-MS
      analyses. Hydrogen cyanide was detected qualitatively by the picric acid test.
      Benzyl ethyl ketone, benzyl methyl ketone, and benzyl alcohol were detected for
      the first time in polydesmidan millipedes. Benzoylnitrile was the major component
      in all three hexane extracts. These compounds are suspected to be active in the
      defensive secretions of these millipede species.

PMID- 20809147
TI  - Analysis of volatile organic compounds in human saliva by a static sorptive
      extraction method and gas chromatography-mass spectrometry.
AB  - Human saliva not only helps control oral health (with anti-microbial proteins),
      but it may also play a role in chemical communication. As is the case with other
      mammalian species, human saliva contains peptides, proteins, and numerous
      volatile organic compounds (VOCs). A high-throughput analytical method is
      described for profiling a large number of saliva samples to screen the profiles
      of VOCs. Saliva samples were collected in a non-stimulated fashion. The method
      utilized static stir bar extraction followed by gas chromatography-mass
      spectrometry (GC-MS). The method provided excellent reproducibility for a wide
      range of salivary compounds, including alcohols, aldehydes, ketones, carboxylic
      acids, esters, amines, amides, lactones, and hydrocarbons. Furthermore,
      substantial overlap of salivary VOCs and the previously reported skin VOCs in the
      same subject group was found in this study by using pattern recognition analyses.
      Sensitivity, precision, and reproducibility of the method suggest that this
      technique has potential in physiological, metabolomic, pharmacokinetic, forensic,
      and toxicological studies of small organic compounds where a large number of
      human saliva samples are involved.

PMID- 20809149
TI  - A strategic approach for cardiac MR left ventricle segmentation.
AB  - Quantitative evaluation of cardiac function from cardiac magnetic resonance (CMR)
      images requires the identification of the myocardial walls. This generally
      requires the clinician to view the image and interactively trace the contours.
      Especially, detection of myocardial walls of left ventricle is a difficult task
      in CMR images that are obtained from subjects having serious diseases. An
      approach to automated outlining the left ventricular contour is proposed. In
      order to segment the left ventricle, in this paper, a combination of two
      approaches is suggested. Difference of Gaussian weighting function (DoG) is newly
      introduced in random walk approach for blood pool (inner contour) extraction. The
      myocardial wall (outer contour) is segmented out by a modified active contour
      method that takes blood pool boundary as the initial contour. Promising
      experimental results in CMR images demonstrate the potentials of our approach.

PMID- 20809148
TI  - GABA, beta-alanine and glycine in the digestive juice of privet-specialist
      insects: convergent adaptive traits against plant iridoids.
AB  - The privet tree, Ligustrum obtusifolium (Oleaceae), defends its leaves against
      insects with a strong lysine-decreasing activity that make proteins non
      nutritive. This is caused by oleuropein, an iridoid glycoside. We previously
      found that some privet-specialist caterpillars adapt by secreting glycine in the
      digestive juice as a neutralizer that prevents the loss of lysine. Here, we
      extended the survey into 42 lepidopteran and hymenopteran species. The average
      concentration of glycine in digestive juice for 11 privet-feeding species (40.396
      mM) was higher than that for 32 non-privet-feeding species (2.198 mM). The
      glycine concentrations exceeded 10 mM in 7 out of 11 privet-feeding species. In
      Macrophya timida (Hymenoptera), it reached 164.8 mM. Three out of the four
      remaining privet-feeding species had other amino acids instead. Larvae of a
      privet-specialist butterfly, Artopoetes pryeri (Lycaenidae), had a high
      concentration (60.812 mM) of GABA. In two other specialists, beta-alanine was
      found. GABA, beta-alanine, and glycine as well as alanine, amines, and ammonium
      ion inhibited the lysine decrease, indicating that amino residues are responsible
      for the inhibition. However, the three amino acids found in the specialists were
      far more effective (20 mM showed 80% inhibition) than the rest (>140 mM was
      required for 80% inhibition). Our results show a clear and rare case of the
      apparent convergent evolution of herbivores' molecular adaptations of feeding on
      a plant with a chemical defense in a manner that minimizes the cost of
      adaptation. The novel role of GABA in plant-herbivore interactions shown here is
      probably the first reported non-neuronal role of animal-derived GABA.

PMID- 20809150
TI  - Peritoneal infusion with cold saline decreased postoperative intra-abdominal
      adhesion formation.

PMID- 20809151
TI  - Prolonged antibiotic treatment does not prevent intra-abdominal abscesses in
      perforated appendicitis.
AB  - BACKGROUND: Children with perforated appendicitis have a relatively high risk of
      intra-abdominal abscesses. There is no evidence that prolonged antibiotic
      treatment after surgery reduces intra-abdominal abscess formation. We compared
      two patient groups with perforated appendicitis with different postoperative
      antibiotic treatment protocols. METHODS: We retrospectively reviewed patients
      younger than age 18 years who underwent appendectomy for perforated appendicitis
      at two academic hospitals between January 1992 and December 2006. Perforation was
      diagnosed during surgery and confirmed during histopathological evaluation.
      Patients in hospital A received 5 days of antibiotics postoperatively, unless
      decided otherwise on clinical grounds. Patients in hospital B received
      antibiotics for 5 days, continued until serum C-reactive protein (CRP) was <20
      mg/l. Univariate logistic regression analysis was performed on intention-to-treat
      basis. p < 0.05 was considered significant. RESULTS: A total of 149 children
      underwent appendectomy for perforated appendicitis: 68 in hospital A, and 81 in
      hospital B. As expected, the median (range) use of antibiotics was significantly
      different: 5 (range, 1-16) and 7 (range, 2-32) days, respectively (p < 0.0001).
      However, the incidence of postoperative intra-abdominal abscesses was similar (p
      = 0.95). Regression analysis demonstrated that sex (female) was a risk factor for
      abscess formation, whereas surgical technique and young age were not.
      CONCLUSIONS: Prolonged use of antibiotics after surgery for perforated
      appendicitis in children based on serum CRP does not reduce postoperative abscess
      formation.

PMID- 20809152
TI  - Colorectal cancer in young patients in Israel: a distinct clinicopathological
      entity?
AB  - PURPOSE: This study was designed to characterize the entity of colorectal cancer
      (CRC) in young patients and to evaluate whether it has any unique epidemiological
      or clinicopathological features. METHODS: The study population consisted of all
      consecutive young (<=50 years old at diagnosis) patients with CRC who were
      diagnosed during the years 1997-2007 and were treated at our institution, and a
      matching group of patients (>50 years at diagnosis). The medical files of these
      patients were reviewed, and the epidemiological, clinical, and pathological
      features of both groups were compared. RESULTS: There were 406 patients: 203 in
      each group. The features of the older group were typical for patients with CRC,
      but the younger group showed female predominance, different ethnic composition,
      prevalence of family history of cancer and hereditary CRC syndromes, and lower
      incidence of polyps. The incidence of left-sided tumors and advanced stages (III
      IV) at diagnosis was higher in the younger patients. Mucinous/signet ring
      histology, grade, stage, lymphatic and vascular invasion were all predictive of
      survival, whereas age was not. CONCLUSIONS: Colorectal cancer in young patients
      was found to display a cluster of unique characteristics but fewer than
      previously reported and young age by itself was not found to impact patient
      outcome.

PMID- 20809155
TI  - Literacy skills and calculated 10-year risk of coronary heart disease.
AB  - BACKGROUND: Coronary heart disease (CHD) is a leading cause of morbidity and
      mortality. Reducing the disease burden requires an understanding of factors
      associated with the prevention and management of CHD. Literacy skills may be one
      such factor. OBJECTIVES: To examine the independent and interactive effects of
      four literacy skills: reading, numeracy, oral language (speaking) and aural
      language (listening) on calculated 10-year risk of CHD and to determine whether
      the relationships between literacy skills and CHD risk were similar for men and
      women. DESIGN: We used multivariable linear regression to assess the individual,
      combined, and interactive effects of the four literacy skills on risk of CHD,
      adjusting for education and race. PARTICIPANTS: Four hundred and nine English
      speaking adults in Boston, MA and Providence, RI. MEASURES: Ten-year risk of
      coronary heart disease was calculated using the Framingham algorithm. Reading,
      oral language and aural language were measured using the Woodcock Johnson III
      Tests of Achievement. Numeracy was assessed through a modified version of the
      numeracy scale by Lipkus and colleagues. KEY RESULTS: When examined individually,
      reading (p = 0.007), numeracy (p = 0.001) and aural language (p = 0.004) skills
      were significantly associated with CHD risk among women; no literacy skills were
      associated with CHD risk in men. When examined together, there was some evidence
      for an interaction between numeracy and aural language among women suggesting
      that higher skills in one area (e.g., aural language) may compensate for
      difficulties in another resulting in an equally low risk of CHD. CONCLUSIONS:
      Results of this study not only provide important insight into the independent and
      interactive effects of literacy skills on risk of CHD, they also highlight the
      need for the development of easy-to use assessments of the oral exchange in the
      health care setting and the need to better understand which literacy skills are
      most important for a given health outcome.

PMID- 20809156
TI  - How to be a good academic leader.
AB  - Individuals who take on leadership positions in academic health science centers
      help facilitate the mission of those institutions. However, they are often chosen
      on the basis of success in the core activities in research, education and patient
      care rather than on the basis of demonstrated leadership and management skills.
      Indeed, most academic leaders in the past have "learned on the job." This
      commentary provides practical advice on how to be an effective leader on the
      basis of the author's experiences as a Division Head and Chief of Medicine. It
      covers six themes (vision, managerial style, knowledge, people skills,
      organizational orientation and personal development) and offers 21 specific
      suggestions, one for each year of the author's leadership. It is hoped that this
      experience-derived advice will help future leaders in academic medicine.

PMID- 20809157
TI  - The effect of medication samples on self-reported prescribing practices: a
      statewide, cross-sectional survey.
AB  - BACKGROUND: The pharmaceutical industry spends billions of dollars annually to
      encourage clinicians to prescribe their medications. Small studies have
      demonstrated that one of the marketing strategies, the distribution of free
      sample medications, is associated with increased use of brand name medication
      over generic medication. OBJECTIVES: To determine the relationship between the
      presence of drug samples in primary care clinics and prescription of preferred
      drug treatments. DESIGN: Cross-sectional survey. PARTICIPANTS: Primary care
      prescribers in the state of Vermont. MAIN MEASUREMENT: Prescribers were presented
      with two clinical vignettes and asked to provide the name of the medication they
      would prescribe in each case. We compared the responses of prescribers with and
      without samples in their clinics. KEY RESULTS: Two hundred six prescribers out of
      the total population of 631 returned the survey and met the eligibility criteria.
      Seventy-two percent of prescribers had sample closets in their clinics. Seventy
      percent of clinicians with samples would prescribe a thiazide diuretic for
      hypertension compared to 91% in those without samples (P<0.01). For managing
      depression 91% of prescribers with samples would have provided a generic
      medication in a patient with no health insurance, compared to 100% of those
      without samples in their clinic (P=0.02). CONCLUSIONS: Clinicians with samples in
      their clinics were less likely to prescribe preferred medications for
      hypertension and depression.

PMID- 20809158
TI  - [Alkaptonuria. Ochronotic arthropathy caused by hereditary metabolic disease].
AB  - Alkaptonuria is a rare hereditary metabolic disease. We report the case of a 72
      year-old woman who suffered from pain and limitation of motion in the major
      joints and spine since middle age because of osteoarthrosis deformans
      alkaptonurica.During knee replacement typical black coloration were detected.
      Early therapy can reduce disease progression but there is no way to heal
      alkaptonuria.

PMID- 20809159
TI  - [Pregnancy-associated osteoporosis. Differential diagnosis of "common"
      musculoskeletal pain during pregnancy and lactation].
AB  - Musculoskeletal pain during pregnancy and lactation is a common finding.
      Differential diagnoses range from"normal" findings to disturbances in bone
      metabolism and pregnancy-associated osteoporosis (PAO). Imaging options are
      limited due to pregnancy, and laboratory diagnostics are time-consuming.
      Treatment of PAO with physiotherapy, pain killers and substitution of vitamin D
      and calcium leads to a rapid recovery from symptoms.

PMID- 20809160
TI  - [Cementless humeral head replacement for dislocation arthropathy of the shoulder
      joint].
AB  - BACKGROUND: Only a few reports in the literature describe that total shoulder
      replacement provides better functional results in dislocation arthropathy than
      hemiarthroplasty. Nevertheless, the risk of aseptic loosening in young and active
      patients is high after long-term follow-up. We evaluated the results of
      cementless humeral head resurfacing in this group. METHODS: We evaluated 29
      patients with dislocation arthropathy who had been followed up for a mean of 39
      months. The mean age at the time of operation was 43.7+/-14.7 years.
      Preoperatively, cuff deficiency was seen in 11 cases. RESULTS: The mean adjusted
      Constant score improved from 16.8+/-15.2% to 78.1+/-21.9%. Negative prognostic
      factors turned out to be female sex, age, cuff tears especially of the
      subscapularis tendon, and previous bone block procedures. Revision was performed
      in five patients, and two developed painful glenoid erosion which required
      conversion to total shoulder arthroplasty. CONCLUSION: Cementless humeral head
      replacement is a viable option in the treatment of dislocation arthropathy.
      Revision can be performed easily since the bone stock has been preserved. On the
      basis of our data, humeral head replacement in patients <40 years with
      dislocation arthropathy offers promising short- to midterm results with an
      acceptable complication rate.

PMID- 20809161
TI  - [Nora's lesion. Discussion of a rare bone proliferation].
AB  - Nora's lesion, also known as "bizarre parosteal osteochondromatous proliferation"
      (BPOP), was first described in 1983 by the pathologist Nora. This lesion is
      defined as a proliferation of the bone. In most cases the lesion emanates from
      the intact cortical substance of short bones. It used to be assigned to reactive,
      heterotopic ossifications. More recent publications described constant genetic
      alterations supposing a tumorous genesis. Nora lesions are mostly found in the
      third or fourth decade of life; a preference of sexes is not described in the
      literature. They are characterized by a typical appearance in radiological
      diagnostics, but the diagnosis is ultimately determined by histopathological
      examination. Surgical resection is the therapy of choice.We report the case of a
      29-year-old patient with an undetermined proliferation of the proximal ulna. The
      diagnosis of a Nora's lesion was made. The therapeutic approach, differential
      diagnosis and corresponding literature are presented and discussed.

PMID- 20809162
TI  - [Clinical pathway for total knee arthroplasty (EGON). II. The impact of enhanced
      patient information].
AB  - PURPOSE: The effects of the introduction of a clinical pathway and enhanced
      patient information on patients' satisfaction were investigated in the current
      study. MATERIAL AND METHODS: In a prospective cohort study patients were
      systematically interviewed about the preparation and the clinical course during
      implantation of a total knee arthroplasty. The study included 132 patients before
      (cohort I) and 128 after (cohort II) introduction of a clinical pathway. All
      patients of cohort II were offered the opportunity to attend an enhanced patient
      information lecture. The collected data were analysed in a descriptive manner.
      Items with more than 10% negative answers constituted the need for improvement.
      RESULTS: Regarding preparation of the operation there was a need for improvement
      of 11 items in cohort I and 4 in cohort II. With respect to the clinical course
      there was a slight increase from 6 to 7 items that required improvement. The
      enhanced information about the treatment and the clinical course were assessed
      positively. Patients were unsatisfied with the individual explanation of the X
      rays. Of 128 patients from cohort II, 58 decided to participate in the
      information session for patients. The patients who had attended were more
      interested in receiving additional information. The success of the operation
      (gain in WOMAC score of at least 20%) showed a substantial effect on patient
      satisfaction. CONCLUSION: With increased patient information the knowledge and
      patient satisfaction within clinical pathways can be improved.

PMID- 20809163
TI  - Statistics in brief: how to assess bias in clinical studies?

PMID- 20809165
TI  - The classic: The chemical constitution of respiration ferment.
AB  - This Classic Article is a reprint of the original work by Otto Heinrich Warburg,
      The Chemical Constitution of Respiration Ferment. An accompanying biographical
      sketch of Otto Heinrich Warburg, PhD, MD, is available at DOI 10.1007/s11999-010
      1533-z . The Classic Article is from Warburg O. The chemical constitution of
      respiration ferment. Science. 1928;68:437-443. Reprinted with permission from
      AAAS.

PMID- 20809164
TI  - Femoral insufficiency fractures associated with prolonged bisphosphonate therapy.
AB  - BACKGROUND: Emerging evidence has linked the long-term use of bisphosphonates
      with femoral insufficiency fractures. It has been suggested that the prolonged
      effect on bone remodeling leads to the accumulation of microfractures and
      weakening of bone. QUESTIONS/PURPOSES: We investigated the association between
      bisphosphonate use and femoral insufficiency fractures. METHODS: We evaluated 100
      patients with low-energy femoral shaft fractures before and after bisphosphonates
      became available for use. Twenty-one consecutive patients who presented between
      January 1995 and February 1997 were compared with 79 consecutive patients who
      presented between January 2007 and February 2009. The radiographs of all 100
      patients were examined for evidence of preexisting insufficiency fractures. We
      identified insufficiency fractures by a transverse fracture line on the tension
      side of the femur with lateral cortical thickening immediately adjacent to the
      fracture. Relevant details from the history were recorded. RESULTS: Forty-one
      patients had an underlying femoral insufficiency fracture, all of whom had been
      receiving bisphosphonate therapy. Among the 21 patients with low-energy femoral
      fractures before the availability of bisphosphonates, none had insufficiency
      fractures. Of the 41 patients with insufficiency fractures, 29 (71%) had
      prodromal pain and 18 (44%) had bilateral insufficiency fractures. Bisphosphonate
      use was associated (odds ratio greater than 1000) with insufficiency fracture.
      The mean duration of bisphosphonate use in patients with insufficiency fractures
      was longer than in patients without fractures (7.1 versus 3.2 years). CONCLUSION:
      Long-term bisphosphonate use is associated with insufficiency fractures of the
      femoral shaft, which commonly present with prodromal thigh pain and may be
      bilateral. These fractures were not seen before bisphosphonates became available
      for use.

PMID- 20809166
TI  - In brief: classifications in brief: Vancouver classification of postoperative
      periprosthetic femur fractures.

PMID- 20809167
TI  - Bisphosphonate remains highly localized after elution from porous implants.
AB  - BACKGROUND: Local elution of zoledronic acid from a porous implant reportedly
      enhances periimplant bone formation and implant fixation. However, there is no
      information in the literature on the extent to which eluted bisphosphonate
      remains localized around the implant or becomes systemically distributed.
      QUESTIONS/PURPOSES: We ascertained to what extent eluted zoledronic acid remains
      local and whether there is systemic exposure after local elution from porous
      implants. METHODS: A hydroxyapatite-coated porous tantalum implant dosed with 100
      MUg (14)C-labeled zoledronic acid was implanted into the left femoral
      intramedullary canal of six dogs. Bone samples near to and distant from the
      implant were harvested from three dogs at 6 weeks and three dogs at 52 weeks. The
      concentration of radiolabeled bisphosphonate in each sample was quantified using
      liquid scintillation spectrophotometry and its distribution in periimplant bone
      was revealed by exposing histologic sections to autoradiography film. RESULTS: In
      all six dogs, the concentration of zoledronic acid in immediate periimplant bone
      was two orders of magnitude higher than in any other sampled tissue, averaging
      732.6 ng/g at 6 weeks and 377.2 ng/g at 52 weeks. Minute amounts of zoledronic
      acid (<= 7.2 ng/g) were detected throughout the skeleton, indicating some escape
      into the circulation after local elution. Autoradiographs revealed the greatest
      concentration of zoledronic acid on and within the implant, with rapid decrease
      short distances away and no uptake within the femoral cortex. CONCLUSIONS:
      Zoledronic acid eluted from an implant remains mainly localized with minimal
      systemic distribution. CLINICAL RELEVANCE: Local bisphosphonate elution reduces
      the risk of systemic side effects and skeletal bisphosphonate exposure.

PMID- 20809168
TI  - Hospital economics of primary THA decreasing reimbursement and increasing cost,
      1990 to 2008.
AB  - BACKGROUND: The introduction of new technology has increased the hospital cost of
      THA. Considering the impending epidemic of hip osteoarthritis in the United
      States, the projections of THA prevalence, and national cost-containment
      initiatives, we are concerned about the decreasing economic feasibility of
      hospitals providing THA. QUESTIONS/PURPOSES: We compared the hospital cost,
      reimbursement, and profit/loss of THA over the 1990 to 2008 time period. METHODS:
      We reviewed the hospital accounting records of 104 patients in 1990 and 269
      patients in 2008 who underwent a unilateral primary THA. Hospital revenue,
      hospital expenses, and hospital profit (loss) for THA were evaluated and compared
      in 1990, 1995, and 2008. RESULTS: From 1990 to 2008, hospital payment for primary
      THA increased 29% in actual dollars, whereas inflation increased 58%. Lahey
      Clinic converted a $3848 loss per case on Medicare fee for service, primary THA
      in 1990 to a $2486 profit per case in 1995 to a $2359 profit per case in 2008.
      This improvement was associated with a decrease in inflation-adjusted revenue
      from 1995 to 2008 and implementation of cost control programs that reduced
      hospital expenses. Reduction of length of stay and implant costs were the most
      important drivers of expense reduction. In addition, the managed Medicare patient
      subgroup reported a per case profit of only $650 in 2008. CONCLUSIONS: If
      hospital revenue for THA decreases to managed Medicare levels, it will be
      difficult to make a profit on THA. The use of technologic enhancements for THA
      add to the cost problem in this era of healthcare reform. Hospitals and surgeons
      should collaborate to deliver THA at a profit so it will be available to all
      patients. Government healthcare administrators and health insurance payers should
      provide adequate reimbursement for hospitals and surgeons to continue delivery of
      high-quality THAs. LEVEL OF EVIDENCE: Level III, economic and decision analysis.
      See Guidelines for Authors for a complete description of levels of evidence.

PMID- 20809169
TI  - Popliteus tendon resection during total knee arthroplasty: an observational
      report.
AB  - BACKGROUND: The contribution provided by the popliteus tendon in patients
      undergoing TKA is poorly defined. Some authors believe the popliteus tendon is
      essential to a well-functioning arthroplasty, while others do not believe it
      provides a critical function. QUESTIONS/PURPOSES: The purposes of this study were
      to (1) evaluate the effect of resecting the popliteus tendon on knee ligament
      balancing in extension and flexion intraoperatively during posterior stabilized
      TKA; and (2) evaluate the effect of resecting the popliteus tendon on load
      distribution on the tibial plateau as determined by an in vitro single limb
      stance model during TKA. METHODS: We randomized 18 patients scheduled for a TKA
      into two groups, A and B. Once component trials were in place, the senior surgeon
      removed himself from the operating table to allow for a blinded trial. The first
      assistant then cut the popliteus tendon in Group A patients but not in Group B
      patients. The senior surgeon then returned to the table to reevaluate the
      subjective balance of the ligamentous structures of the knee in both extension
      and in flexion. A parallel cadaveric study was also completed using a
      sophisticated instrumented tibial plateau sensor in three knees. RESULTS: The
      senior surgeon was unable to detect a difference in the knee stability between
      knees with transected popliteal tendons and those with intact popliteal tendons.
      In vitro studies showed there was no change in load distribution between the
      medial and lateral plateaus once the popliteus tendon was transected.
      CONCLUSIONS: Resection of the popliteus tendon does not appear to change the
      static balance of the knee. LEVEL OF EVIDENCE: Level II, prognostic study. See
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 20809170
TI  - Modular femoral sleeve and stem implant provides long-term total hip
      survivorship.
AB  - BACKGROUND: A femoral implant with a modular sleeve and stem has been designed to
      allow independent and complete metaphyseal-diaphyseal fit and fill as well as
      independent rotation to accommodate anteversion at the time of THA.
      QUESTIONS/PURPOSES: In a prospective study we asked whether such a modular
      femoral sleeve and stem implant used during THA could provide (1) high long-term
      survivorship; (2) radiographically stable implants without radiolucencies, stress
      shielding, or osteolysis; and (3) high clinical scores in patients 15 to 20 years
      after a primary THA. PATIENTS AND METHODS: We prospectively evaluated 31 hips
      that underwent a primary THA using a modular femoral component for clinical
      outcome (Harris hip score) and radiographic outcome (implant stability, femoral
      loosening, osteolysis and stress shielding) at a minimum followup of 15 years
      (mean, 17 years; range, 15-20.2 years). RESULTS: There were no femoral revisions
      for aseptic loosening; all hips had radiographic evidence of bone ingrowth. Two
      well-ingrown components were revised for late hematogenous infection. Some degree
      of proximal femoral disuse atrophy from stress shielding occurred in 23 hips
      (74%) but was nonprogressive and did not result in any failures or complications.
      Femoral osteolysis occurred in 18 hips (58%), but we cannot definitively
      determine whether or not the modular junction contributed to this. CONCLUSIONS:
      These data suggest this modular femoral stem can provide long-term survivorship
      with no cases of aseptic loosening at 15 to 20 years after primary THA. However,
      it may be prudent when using this femoral stem to consider an articulation with
      an alternative bearing or, if the modularity is not needed to address femoral
      anteversion and metaphyseal-diaphyseal mismatch, to consider a nonmodular femoral
      stem. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors
      for a complete description of levels of evidence.

PMID- 20809171
TI  - Liner exchange and bone grafting: rare option to treat wear & lysis of stable
      TKAs.
AB  - BACKGROUND: Liner exchange and bone grafting are commonly performed for wear and
      osteolysis around well-fixed modular acetabular components that otherwise would
      require structural allografting and revision THA. However, liner exchange in the
      face of substantial lysis around TKA has been performed rarely with reports of
      failure rates of up to 25% at 3 year followup. QUESTIONS/PURPOSES: We therefore
      evaluated the technique of liner exchange and bone grafting for cases of wear and
      extensive osteolysis around TKAs in which the components were well-fixed and well
      aligned to determine (1) rerevision rates; (2) fate of the bone graft; (3)
      radiographic loosening rates; and (4) functional scores. METHODS: We
      retrospectively reviewed 22 patients (25 knees) who underwent revision TKA with
      exchange of the modular polyethylene insert and bone grafting in cases with well
      fixed components and large areas of osteolysis (up to 54 cm(2) on a single
      projection) at the time of revision. The average area of osteolysis was 21 cm(2)
      and 10 cm(2) on the AP projection of the femur and tibia, respectively. On the
      lateral projection, the average area of osteolysis for the femur and tibia was 22
      cm(2) and 9.3 cm(2). Minimum clinical and radiographic followup was 22 and 22
      months (average, 61 and 59; range, 22-142 and 22-130, respectively). RESULTS: One
      of the 25 knees was revised for aseptic loosening or recurrence of osteolysis. On
      radiographs, 84.6% and 70% of femoral and tibial osteolytic lesions,
      respectively, showed evidence of complete or near complete graft incorporation.
      The remaining lesions showed evidence of partial graft incorporation with the
      exception of one tibial lesion, which was in the revised case. All other
      components were well fixed with no evidence of radiographic loosening.
      CONCLUSIONS: In this selected series of cases with extensive osteolysis around
      well-fixed and well-aligned TKAs, liner exchange and bone grafting provided
      durable midterm results with extensive graft incorporation. LEVEL OF EVIDENCE:
      Level IV, therapeutic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 20809172
TI  - A monoblock porous tantalum acetabular cup has no osteolysis on CT at 10 years.
AB  - BACKGROUND: Aseptic osteolysis has been the single most important factor limiting
      the longevity of a THA. A great deal of attention has been focused on the
      development of implants and materials that minimize the development of
      osteolysis. The monoblock porous tantalum acetabular cup was designed to minimize
      osteolysis, but whether it does so is unclear. QUESTIONS/PURPOSES: We evaluated
      the incidence of osteolytic lesions after THA using a monoblock porous tantalum
      acetabular component. METHODS: We retrospectively reviewed 51 patients who had a
      THA using a monoblock porous tantalum acetabular cup. At a minimum of 9.6 years
      postoperatively (average, 10.3 years; SD, 0.2 years; range, 9.6-10.8 years), a
      helical CT scan of the pelvis using a metal suppression protocol was obtained.
      This scan was evaluated for the presence of osteolysis. RESULTS: We found no
      evidence of osteolysis on CT scan at an average of 10.3 years. CONCLUSIONS:
      Osteolysis appears not to be a major problem at 10 years with this monoblock
      porous tantalum acetabular component, but longer term followup will be required
      to determine whether these findings persist. LEVEL OF EVIDENCE: Level IV,
      therapeutic study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 20809173
TI  - Rare case of dysphagia.
AB  - Wound botulism is exceedingly rare and occurs almost exclusively among injection
      drug users. In 2008 there was a case of wound botulism in a noninjecting drug
      user reported to the Centers for Disease Control and Prevention (CDC). We report
      a case of a Caucasian male developing dysphagia due to wound botulism after
      having a motorcycle accident that left him with open fractures. The CDC was
      contacted and the patient was transferred to medical intensive care unit to be
      emergently started on hepatavalent Clostridium botulinum antitoxin. Early
      suspicion of wound botulism is essential for effective therapy with antitoxin in
      this life-threatening disease. If not suspected, this patient would likely have
      died. Nevertheless, the delay in diagnosis and treatment resulted in the
      patient's suffering dysphagia and neurological deficits. The patient required a
      percutaneous endoscopic gastrostomy tube and months of dysphagia therapy,
      supportive care, and rehabilitation. Our aim is to increase the awareness for
      wound botulism when a patient presents with dysphagia and diplopia after
      suffering open wounds. If suspected early, the morbidity and mortality from this
      disease can be prevented.

PMID- 20809175
TI  - Invasive IPMN and MCN: same organ, different outcomes?
AB  - BACKGROUND: The efficacy of surgery for invasive mucinous neoplasms is unclear.
      We examined the natural history of invasive mucinous cystic neoplasms (MCN) and
      invasive intraductal papillary mucinous neoplasms (IPMN) in patients who
      underwent pancreatic resection. METHODS: The Surveillance, Epidemiology, and End
      Results (SEER) database (1996-2006) was queried for cases of resected invasive
      MCN and IPMN. Demographics, tumor characteristics, and overall survival were
      examined using log-rank analysis and multivariate Cox regression model. RESULTS:
      Of 185 MCN cases and 641 IPMN cases, 73% and 48%, respectively, were women (P <
      0.0001). Most (73%) IPMN were in the head of the pancreas; most (64%) MCN were in
      the tail/body (P < 0.0001). Lymph node metastasis was more common for IPMN than
      MCN (46% vs. 24%, P < 0.0001). Overall survival after resection was better for
      patients with stage I MCN vs. stage I IPMN (P = 0.0005), and it was better for
      patients with node-negative MCN vs. node-negative IPMN (P = 0.0061). There was no
      significant difference in survival of patients with stage IIA MCN vs. stage IIA
      IPMN (P = 0.5964), stage IIB MCN vs. stage IIB IPMN (P = 0.2262), or node
      positive MCN vs. node-positive IPMN (P = 0.2263). Age older than 65 years
      (hazards ratio (HR) 1.71, P = 0.0046), high tumor grade (HR 2.68, P < 0.0001),
      higher T stage (HR 2.11, P < 0.0001), and IPMN histology (HR 1.90, P = 0.0040)
      predicted worse outcome in node-negative patients. CONCLUSIONS: Our findings
      suggest that survival is better after resection of invasive MCN versus invasive
      IPMN when disease is localized within the pancreas, but this difference
      disappears in the presence of nodal metastasis or extrapancreatic extension.

PMID- 20809174
TI  - Biochemistry of the anterior, medial, and posterior genioglossus in the aged rat.
AB  - Age-related tongue weakness may contribute to swallowing deficits in the elderly.
      One contributing factor may be an alteration in muscle-fiber-type properties with
      aging. However, it is not clear how muscle fiber types within the aged tongue may
      vary from those found in young adults, or how fiber types may vary across the
      anteroposterior axis of the extrinsic tongue muscles. We examined the myosin
      heavy chain (MHC) composition of anterior, medial, and posterior sections of the
      genioglossus muscle (GG) in ten old male Fischer 344/Brown Norway rats and
      compared findings to previously reported data from young adult male rats.
      Significant differences (p < 0.01) between young adult and old rats were found in
      the distribution of MHC isoforms along the anteroposterior axis of the muscle. In
      the anterior, medial, and posterior regions, there was a significantly smaller
      proportion of type IIb MHC in the old rat GG muscles, while the proportion of
      type IIx MHC was significantly greater. In the medial region, the proportion of
      type I MHC was found to be significantly greater in the old rats. Thus, we found
      a shift to more slowly contracting muscle fibers in the aged rat tongue.

PMID- 20809176
TI  - Predictors of inpatient death and complications among postoperative elderly
      patients with metastatic brain tumors.
AB  - OBJECTIVE: Risks of brain surgery in elderly patients with brain metastases are
      not well defined. This study was designed to quantify the postoperative risk for
      these patients after brain surgery for metastatic disease to the brain. METHODS:
      We performed a retrospective analysis of the Nationwide Inpatient Sample (1998
      2005). Patients aged 65 years or older who underwent tumor resection of brain
      metastases were identified by ICD-9 coding. Primary outcome was inpatient death.
      Other outcomes included systemic postoperative complications, length of stay
      (LOS), and total charges. RESULTS: A total of 4,907 patients (53.6% men) were
      identified. Mean age was 72.1 years. Mean Charlson comorbidity score was 7.8.
      Inpatient mortality was 4%. The most common adverse events were pulmonary
      complications (3.4%). Mean length of stay was 9.2 days. Mean total charges were
      $57,596.39. In multivariate analysis, patients up to age 80 years had no
      significantly greater odds of inpatient death, relative to their 65- to 69-year
      old counterparts. Each 1-point increase in Charlson score was associated with 12%
      increased odds of death, 0.52 days increased LOS, and $1,710.61 higher hospital
      charges. Postoperative pulmonary complications, stroke, or thromboembolic events
      increased LOS and total charges by up to 9.6 days and $57,664.42, respectively.
      These associations were statistically significant (P < 0.05). CONCLUSIONS:
      Surgical resection of brain metastases among the elderly up to the ninth decade
      of life is feasible. Age older than 80 years and higher Charlson comorbidity
      scores were found to be important prognostic factors for inpatient outcome.
      Incorporating these factors into preoperative decision making may help to select
      appropriately those elderly candidates for neurosurgical intervention.

PMID- 20809177
TI  - Extent of gastric resection impacts patient quality of life: the Dysfunction
      After Upper Gastrointestinal Surgery for Cancer (DAUGS32) scoring system.
AB  - BACKGROUND: Quality of life is an important outcome measure in the care of
      patients with cancer. We developed a new scoring system specifically for the
      evaluation of patients with upper gastrointestinal cancer and postoperative
      gastrointestinal dysfunction. This study was undertaken to evaluate the scoring
      system's validity in comparing outcomes after gastric resection. MATERIALS AND
      METHODS: Patients with gastric cancer, 3 months to 3 years postoperatively, were
      surveyed using the survey instrument. Postoperative dysfunction scores and the
      status of resuming activities of daily living were compared with the surgical
      procedure performed by analysis of variance and multiple-comparison techniques.
      RESULTS: Of 211 patients surveyed, 165 (119 men, 46 women; mean age, 65.1 +/-
      10.5 years) responded. Procedures included distal gastrectomy in 100, total
      gastrectomy in 57, and pylorus-preserving gastrectomy in 8. The overall
      dysfunction score was 61.8 +/- 15.5. The dysfunction score was 58.9 +/- 15.0
      after distal gastrectomy, 66.8 +/- 14.1 after total gastrectomy, and 62.4 +/-
      21.6 after pylorus-preserving gastrectomy. These values differed significantly
      among the groups (P = .007). Dysfunction scores according to postoperative
      activity status were 49.1 +/- 15.6 in 71 patients who resumed their activities,
      56.9 +/- 15.7 in 39 patients with reduced activities, 57.3 +/- 8.8 in 15 patients
      with minimal activities, and 63.3 +/- 11.8 (P < .05) in 16 patients who did not
      resume activities because of poor physical condition. CONCLUSIONS: This scoring
      system for postoperative gastrointestinal dysfunction provides an objective
      measure of dysfunction related to specific surgical procedures and correlates
      with activities of daily living in the postoperative period.

PMID- 20809178
TI  - In their own words: assessment of satisfaction with residential location among
      migrants in Nairobi slums.
AB  - Using qualitative data collected from a sample of rural-urban migrants over the
      age of 15 in two Nairobi slums interviewed in 2008, this paper discusses the
      migrants' extent of satisfaction with their residential location and decision to
      migrate. The study sheds light on why people continue to migrate to, and stay in,
      the rapidly growing slum settlements despite the high levels of poverty and poor
      health conditions in these areas. Tenure status is related to satisfaction for
      all ages. Environmental factors were frequently mentioned as a source of
      dissatisfaction. Life cycle and 'age-cohort effects' may also affect satisfaction
      for different age groups in terms of who is satisfied as well as the issues that
      are considered for satisfaction. High levels of dissatisfaction with slum life
      may be responsible for high out-migration in slum areas, although it does not
      mean that those who remain do so because they are satisfied. At the same time,
      challenges associated with slum life do not automatically signify
      dissatisfaction. Perceived success, as well as conditions in the area of origin
      can be used to explain and understand satisfaction/dissatisfaction with slum
      life. Satisfaction with migration and residential location may be related not
      only to the destination place, but also to events in the area of origin.

PMID- 20809179
TI  - 5-S-GAD attenuates Fe2+-induced lipid peroxidation and cell death in a neuronal
      cell model.
AB  - Iron accumulation in brain is associated with a number of common
      neurodegenerative disorders. N-beta-alanyl-5-S-glutathionyl-3,4
      dihydroxyphenylalanine (5-S-GAD), a novel catechol derivative, was isolated from
      adult flesh fly as a defense substance. We examined the effect of 5-S-GAD on Fe2+
      induced lipid peroxidation and cell death in PC12 cells. Treatment of PC12 cells
      with Fe2+ (1-20 MUM) for 24 h induced lipid peroxidation and cell death in a dose
      dependent manner. Butylated hydroxyanisole and alpha-tocopherol inhibited Fe2+
      induced lipid peroxidation and cell death. 5-S-GAD inhibited Fe2+-induced lipid
      peroxidation and cell death. 5-S-GAD protected PC12 cells from Fe2+-induced cell
      death possibly by blocking lipid peroxidation.

PMID- 20809180
TI  - Molecular mechanisms by which saturated fatty acids modulate TNF-alpha expression
      in mouse macrophage lineage.
AB  - Many macrophage functions are modulated by fatty acids (FAs), including cytokine
      release, such as tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is of great
      interest due to its role in the inflammation process observed in several diseases
      such as rheumatoid arthritis, atherosclerosis, and obesity. However, the
      mechanisms by which FA effects occur have not been completely elucidated yet. In
      this study, we used a mouse monocyte lineage (J774 cells) to evaluate the effect
      of 50 and 100 MUM of saturated (palmitic and stearic acids), monounsaturated
      (oleic acid) and polyunsaturated (linoleic acid) FAs on TNF-alpha production.
      Alterations in gene expression, poly(A) tail length and activation of
      transcription factors were evaluated. Oleic and linoleic acids, usually known as
      neutral or pro-inflammatory FA, inhibited LPS-induced TNF-alpha secretion by the
      cells. Saturated FAs were potent inducers of TNF-alpha expression and secretion
      under basal and inflammatory conditions (in the presence of LPS). Although the
      effect of the saturated FA was similar, the mechanism involved in each case seem
      to be distinct, as palmitic acid increased EGR-1 and CREB binding activity and
      stearic acid increased mRNA poly(A) tail. These results may contribute to the
      understanding of the molecular mechanisms by which saturated FAs modulate the
      inflammatory response and may lead to design of associations of dietary and
      pharmacological strategies to counteract the pathological effects of TNF-alpha.

PMID- 20809182
TI  - Identification of a novel mouse brachyury (T) allele causing a short tail
      mutation in mice.
AB  - Mutations in T-box genes are associated with numerous disease states in humans.
      The objective of this paper was to characterize the T(shao), a specific T-box
      mutation, in mice. T(shao), a short-tailed mutant mouse strain in a B6
      background, was obtained by ethylnitrosourea mutagenesis. Microsatellite genomic
      scans mapped the location of the mutation. RT-PCR was used to amplify the
      identified region and the product was sequenced. DNA of the region was sequenced
      and scanned for mutations. Tails of T(shao) mice were mostly curly with tail
      length ranging from less than 1 cm (tail bud) to half of the normal length.
      T(shao) presented single dominance gene inheritance, and homozygous mutant mice
      died approximately at E10. Scans of the F2 generation mapped the mutant gene to
      chromosome 17, near D17Mit143. The Brachyury (T) gene was identified as a
      potential candidate gene in this location. To confirm this, RT-PCR was performed
      on RNA from intercrossed 8.5-day embryos, and products were sequenced. A 67
      nucleotide deletion in exon 2 of the mutant T gene was identified. Further
      sequencing of the genomic DNA from this region identified a T to A transversion
      at the 67th nucleotide of exon 2. The T(shao) mutation is a result of a deletion
      in exon 2 causing the early termination and loss of function of protein encoded
      by the T gene, manifesting as a short tail phenotype.

PMID- 20809181
TI  - Characterization of Myelin Sheath F(o)F(1)-ATP synthase and its regulation by
      IF(1).
AB  - F(o)F(1)-ATP synthase is the nanomotor responsible for most of ATP synthesis in
      the cell. In physiological conditions, it carries out ATP synthesis thanks to a
      proton gradient generated by the respiratory chain in the inner mitochondrial
      membrane. We previously reported that isolated myelin vesicles (IMV) contain
      functional F(o)F(1)-ATP synthase and respiratory chain complexes and are able to
      conduct an aerobic metabolism, to support the axonal energy demand. In this
      study, by biochemical assay, Western Blot (WB) analysis and immunofluorescence
      microscopy, we characterized the IMV F(o)F(1)-ATP synthase. ATP synthase activity
      decreased in the presence of the specific inhibitors (olygomicin, DCCD, FCCP,
      valynomicin/nigericin) and respiratory chain inhibitors (antimycin A, KCN),
      suggesting a coupling of oxygen consumption and ATP synthesis. ATPase activity
      was inhibited in low pH conditions. WB and microscopy analyses of both IMV and
      optic nerves showed that the Inhibitor of F(1) (IF(1)), a small protein that
      binds the F(1) moiety in low pH when of oxygen supply is impaired, is expressed
      in myelin sheath. Data are discussed in terms of the role of IF(1) in the
      prevention of the reversal of ATP synthase in myelin sheath during central
      nervous system ischemic events. Overall, data are consistent with an energetic
      role of myelin sheath, and may shed light on the relationship among demyelination
      and axonal degeneration.

PMID- 20809183
TI  - Complete response after sorafenib therapy for hepatocellular carcinoma in an HIV
      HBV co infected patient: Possible synergy with HAART ? A case report.
AB  - A significant proportion of HIV patients, ranging between 5-67%, are co-infected
      with hepatitis B virus (HBV). Several studies suggest an increasing incidence of
      hepatocellular carcinoma (HCC) in HIV infected individuals. We report the case of
      a 69 years old male co infected with HBV and HIV who developed HCC. The patient
      was unfit for curative approach and he underwent three sessions of transcatheter
      arterial chemoembolisation (TACE). After the last session the disease assessment
      showed progression and sorafenib therapy was initiated. Highly active
      antiretroviral therapy (HAART) was continued during sorafenib treatment. The
      patient achieved a radiological complete response (CR) after 6 months of therapy
      and remained with no sign of HCC progression at subsequent assessment. Meanwhile,
      patient's HIV and HBV infections remained stable. Regarding toxicity the patient
      developed grade 3 hand foot skin reaction (HFSR) that required 50% dose reduction
      of sorafenib, grade 3 hypertension and grade 2 diarrhea. In conclusion this is
      the first case of successful treatment of HCC in a HIV-HBV co-infected patient
      and only the second report of the co administration of sorafenib with HAART.

PMID- 20809184
TI  - Clinical characterization and prognostic factors of primary lymphoma of bone in
      case of Chinese patients.
AB  - Primary lymphoma of bone (PLB) is a very rare neoplasm. Many aspects of this
      entity have not been well defined or reported in Chinese population. The purpose
      of our study is to identify the prognostic factors of PLB. Twenty-five patients
      newly diagnosed with PLB were included in this retrospective study. The main
      pathologic subtype of PLB was diffuse large B-cell lymphoma (DLBCL), followed by
      anaplastic large-cell lymphoma. The pelvis was the most commonly involved site
      (13 cases, 52%). The 5-year overall survival (OS) rate was 55.0%. Cox regression
      analysis demonstrated that IPI score was an independent prognostic factor of
      survival (RR = 8.46, P = 0.013). The mean survival time (MST) was 90.3 months for
      patients with radiation and 54.0 months for those without radiotherapy (P =
      0.033). Patients who received the anti-CD20 monoclonal antibody rituximab therapy
      showed a favorable survival trend, but not significant benefit (MST: 74.5 months
      vs. 68.6 months, P = 0.149). Some clinical characteristics in the Chinese
      population are different from those in westerners. The frequency of T-cell
      subtypes is higher, and the pelvis is the most commonly involved site.
      Irradiation plus chemotherapy may be better than chemotherapy alone. The role of
      bisphosphonates and rituximab in PLB therapy warrants further investigation.

PMID- 20809185
TI  - Potential role of serum level of soluble CD44 and IFN-gamma in B-cell chronic
      lymphocytic leukemia.
AB  - Evidence indicates that the slowly expanding population of B cells that
      characterizes chronic lymphocytic leukemia (CLL) results primarily from defects
      in responses to cytokines. We evaluated the prognostic value of soluble CD44 and
      IFN-gamma in B-cell chronic lymphocytic leukemia (B-CLL) and analyzed their
      source and regulation secretion in B-CLL clones in vitro. Levels of soluble CD44
      standard (sCD44s) and IFN-gamma were analyzed by enzyme-linked immunosorbent
      assay. B-CLL cells were separated and stimulated in vitro for the detection of
      both markers. Serum levels of sCD44s and IFN-gamma were significantly elevated in
      patients with B-CLL in comparison with normal persons. Elevated levels of sCD44s
      and IFN-gamma were associated with an advanced disease as reflected by increased
      values as stage progress. In B-CLL, sCD44s as well as IFN-gamma was shed from
      leukemia cells as shown by in vitro cultures. Stimulation of B-CLL clones results
      in a proliferation-associated increased secretion of sCD44s and IFN-gamma. B-CLL
      clones from advanced-stage patients are characterized by an increased capacity
      for proliferation and production of both markers in comparison with early-stage
      patients. Our present results suggest that sCD44 and IFN-gamma may be of major
      importance in the pathogenesis of B-CLL, and inhibition of the effects of sCD44
      and IFN-gamma could be a potential therapeutic strategy.

PMID- 20809186
TI  - Expressions of matrix metalloproteinase-7 and matrix metalloproteinase-14
      associated with the activation of extracellular signal-regulated kinase1/2 in
      human brain gliomas of different pathological grades.
AB  - The purpose of this study is to determine whether the expressions of MMP-7 and
      MMP-14 are associated with the ERK 1/2 signaling pathway in human brain gliomas
      of different pathological grades. Immunohistochemistry and western blot methods
      were used to determine the expressions of MMP-7, MMP-14 and the phosphorylation
      status of ERK1/2 in 73 cases of human brain glioma specimens and two cases of
      normal brain tissues. Results indicated that the protein expression levels of MMP
      7, MMP-14 and ERK1/2 phosphorylation level were all elevated with the increasing
      pathological grades in brain glioma tissues, and correlation assay indicated that
      the level of ERK1/2 phosphorylation was positively correlated with protein
      expression levels of MMP-7 and MMP-14 in gliomas of different pathological grades
      respectively. Moreover, the impact of ERK1/2 inhibitor U0126 on the expressions
      of MMP-7 and MMP-14 was examined in human U87 glioma cells by western blot
      analysis. The expressions of MMP-7 and MMP-14 were significantly decreased in
      human U87 glioma cells after treatment with ERK1/2 inhibitor U0126. The above
      results suggest that the expressions of MMP-7 and MMP-14 may be associated with
      activation of ERK1/2 signaling pathway in human brain gliomas of different
      pathological grades.

PMID- 20809187
TI  - Can we see epithelium tissue structure below the surface using an optical probe?
AB  - This paper answers the question of whether it is possible to detect changes below
      the surface in epithelium layered structures using a Stochastic Decomposition
      Method (SDM) that models the scattered light reflected from the layered structure
      over an area (2-D scan) illuminated by an optical sensor (fibre) emitting light
      at either one wavelength or with white light. Our technique correlates the
      differential changes in the reflected tissue texture with the morphological and
      physical changes that occur in the tissue occurring inside the structure. This
      work has great potential for detecting changes in mucosal structures and may lead
      to enhanced endoscopy when the disease is developing to the outside of the
      mucosal structure and hence becoming hidden during colonoscopy or endoscopic
      examination. Tests are performed on layered tissue phantoms, and the results
      obtained show great effectiveness of the model and method in picking up changes
      in the morphology of the layered tissue phantoms occurring below the surface. We
      also establish the robustness of the model to changes in viewing depth by testing
      it on phantoms viewed at different depths. We show that the model is robust to
      within a 4-mm-deep viewing range.

PMID- 20809189
TI  - The "cord sign" in cerebral venous thrombosis associated with high plasma levels
      of factor VIII.
AB  - BACKGROUND: Cerebral venous thrombosis (CVT) is a potentially life-threatening
      condition that requires acute recognition and treatment. Diagnosis of CVT is
      challenging and requires a high index of clinical suspicion. The finding of the
      "cord sign" in a non-contrast cranial CT is useful for the rapid recognition of
      CVT in the emergency setting. METHODS: We describe a patient with CVT in whom the
      "cord sign" and elevated factor VIII (FVIII) plasma levels were both present.
      RESULTS: A 45-year-old Caucasian man was brought to the emergency room with
      headache and a focal seizure. His neurological examination was non-focal. During
      his evaluation in the ER, a non-contrast cranial CT showed increased density of
      cortical veins ("cord sign"), vein of Galen, and superior sagittal, transverse
      and straight sinuses. A brain MRI demonstrated a flow signal void in the superior
      sagittal sinus, prominent cortical veins, asymmetric flow signal in the right
      transverse sinus, and subarachnoid hemorrhage adjacent to the superior sagittal
      sinus. Laboratory work-up was unremarkable and only revealed elevation of FVIII
      plasma levels. CONCLUSIONS: We report the first case of CVT with the "cord sign"
      and concomitant elevated FVIII. Early recognition of the "cord sign" is warranted
      for the emergency diagnosis and treatment of CVT.

PMID- 20809190
TI  - Single-access transumbilical laparoscopic appendectomy and cholecystectomy using
      new curved reusable instruments: a pilot feasibility study.
AB  - BACKGROUND: The umbilicus can be considered as the embryological opening for
      single-access laparoscopic procedures. We report on single-access transumbilical
      laparoscopic appendectomy (SATLA) and cholecystectomy (SATLC), performed using
      new curved reusable instruments. PATIENTS AND METHODS: A retrospective review of
      a prospectively maintained database of 30 patients who underwent SATLA and 20
      patients who underwent SATLC between May and November 2009 was undertaken. All
      procedures were performed with an 11-mm nondisposable trocar for the scope, and
      curved reusable instruments (Karl Storz-Endoskope, Tuttlingen, Germany) placed
      transumbilically without trocars. Outcome measures were conversion to standard
      laparoscopy, operative time, scar length, complications, hospital stay, and use
      of pain medication. RESULTS: All SATLA patients had acute appendicitis, and SATLC
      patients had symptomatic gallstones (15), chronic cholecystitis (3), and acute
      cholecystitis (2). No extraumbilical trocars were necessary. Mean total operative
      times were 57.3 +/- 15.9 min (SATLA) and 73.9 +/- 20.1 min (SATLC). Mean
      laparoscopic times were 39 +/- 13.1 min (SATLA) and 57.5 +/- 18.9 min (SATLC).
      Mean scar lengths were 14.8 +/- 2.2 mm (SATLA) and 15.8 +/- 2.3 mm (SATLC). Five
      SATLA patients and one SATLC patient developed postoperative complications. Mean
      hospital stay was 2.9 +/- 1.3 days for SATLA patients and 1.8 +/- 0.8 days for
      SATLC patients. Pain medication used was minimal. At the minimum follow-up of 3
      months no late complications were registered. CONCLUSIONS: SATLA and SATLC can be
      performed safely using curved reusable instruments, which helps avoid the
      conflict between the surgeon's hands or between the instruments' tips and allows
      the surgeon to operate in an ergonomic position. The reusable instruments kept
      the cost similar to that of classic laparoscopy.

PMID- 20809191
TI  - Matrix solid-phase dispersion followed by gas chromatography-mass spectrometry
      for the determination of triclosan and methyl triclosan in sludge and sediments.
AB  - An expeditious method for the determination of triclosan (TCS) and methyl
      triclosan (MTCS) in sludge and sediment samples is presented. Extraction and
      cleanup steps were integrated in the same process using matrix solid-phase
      dispersion as sample preparation technique. Effects of different variables on the
      efficiency and the selectivity of the sample preparation process are discussed.
      Under final working conditions, samples (0.5 g) were dispersed with diatomaceous
      earth (1 g) and transferred to a polypropylene syringe containing 2 g of silica
      impregnated with sulphuric acid (15%, w:w). Analytes were recovered with 10 mL of
      dichloromethane. After solvent exchange to ethyl acetate, TCS was converted into
      the tert-butyldimethylsilyl derivative, and the extract was analysed by gas
      chromatography-mass spectrometry, without any additional cleanup. Obtained
      recoveries, for sludge and sediment samples spiked at different concentration
      levels, ranged from 86% to 113%, with associated standard deviations between 2
      and 13%. Limits of quantification of the global method were 6 and 7 ng g(-1) for
      MTCS and TCS, respectively. Both compounds were detected in all the processed
      sludge samples with maximum concentrations of 191 ng g(-1) (MTCS) and 2,640 ng g(
      1) (TCS). The parent bactericide was also found in some sediment samples at
      concentrations up to 200 ng g(-1).

PMID- 20809188
TI  - Unfractionated heparin: multitargeted therapy for delayed neurological deficits
      induced by subarachnoid hemorrhage.
AB  - Aneurysmal subarachnoid hemorrhage (SAH) is associated with numerous "delayed
      neurological deficits" (DNDs) that have been attributed to multiple
      pathophysiological mechanisms, including ischemia, microthrombosis, free radical
      damage, inflammation, and vascular remodeling. To date, effective prophylactic
      therapy for SAH-induced DNDs has been elusive, due perhaps to the multiplicity of
      mechanisms involved that render typical, single-agent therapy seemingly futile.
      We hypothesized that heparin, which has multiple underappreciated salutary
      effects, might be useful as a multitargeted prophylactic agent against SAH
      induced DNDs. We performed a comprehensive review of the literature to evaluate
      the potential utility of heparin in targeting the multiple pathophysiological
      mechanisms that have been identified as contributing to SAH-induced DNDs. Our
      literature review revealed that unfractionated heparin can potentially antagonize
      essentially all of the pathophysiological mechanisms known to be activated
      following SAH. Heparin binds >100 proteins, including plasma proteins, proteins
      released from platelets, cytokines, and chemokines. Also, heparin complexes with
      oxyhemoglobin, blocks the activity of free radicals including reactive oxygen
      species, antagonizes endothelin-mediated vasoconstriction, smooth muscle
      depolarization, and inflammatory, growth and fibrogenic responses. Our review
      suggests that the use of prophylactic heparin following SAH may warrant formal
      study.

PMID- 20809192
TI  - [Current status of tinnitus research and treatment].

PMID- 20809193
TI  - [Music therapy for noisiform tinnitus. Concept development and evaluation].
AB  - BACKGROUND: Music therapy in chronic tonal tinnitus according to the
      "Heidelberger model" presents an effective treatment, which is substantiated by
      neuroscientific and psychological evaluation. METHOD: The music therapy approach
      was specifically extended to include noisiform tinnitus, taking sound quality and
      cardiovascular influences into consideration. Outcome criteria were psychological
      tinnitus load, psychophysiologic parameters and brain imaging procedures.
      RESULTS: Psychological outcomes of the pilot study indicate that 21 of the 23
      patients (i.e. more than 90%) achieved a reliable reduction of symptoms (TQ
      scores: pre: 40.1 +/- 11.4; post: 27.9 +/- 12.8; at 3-month-follow-up: 24.0 +/-
      12.2). Results of the imaging examinations demonstrated neuroplastic changes in
      the putamen and insula. Psychophysiological measurements indicate cardiovascular
      influences on noisiform tinnitus. DISCUSSION: Therapy success depends on the
      sound quality of the tinnitus; therefore, any treatment should take this into
      consideration. Cardiovascular influences were important insofar as active control
      of the heart rate was an important predictor of long-term therapy outcome.
      Overall, brain imaging data confirm the top-down-model of tinnitus generation.

PMID- 20809194
TI  - Understanding the relationships between health outcomes in generalized anxiety
      disorder clinical trials.
AB  - BACKGROUND AND AIMS: The Wilson-Cleary health outcomes model is a hypothesized
      pathway linking traditional clinical variables to health-related quality of life
      (HRQL). This study tested the application of the Wilson-Cleary model to a patient
      population with generalized anxiety disorder (GAD) using longitudinal clinical
      trial data. METHODS: These secondary analyses pooled data from three similar 8
      week, placebo-controlled, double-blind, randomized, multicenter trials of
      quetiapine XR therapy in GAD. Relevant health assessments for the model concepts
      included the Clinical Global Impression-Severity of Illness, Hamilton Rating
      Scale for Anxiety, the Pittsburgh Sleep Quality Index and Quality of Life
      Enjoyment and Satisfaction Questionnaire-Short Form. A lagged path model tested
      whether the hypothesized relationships at baseline and week 8 between the
      concepts of the adapted Wilson-Cleary model were consistent with the observed
      data. RESULTS: The resulting model fit the data (RMSEA = 0.077; CFI = 0.98; NFI =
      0.96) and explained 56% of the variance in overall quality of life assessment at
      baseline and 69% of the variance in this assessment at week 8. Moderate to strong
      relationships between the adjacent hypothesized concepts support the specified
      model. CONCLUSION: This adapted Wilson-Cleary model for health outcomes validated
      in GAD should improve the understanding and usefulness of health status
      measurements in this condition and increase the applications of this model to
      other clinical trial data.

PMID- 20809195
TI  - European French-speaking study from the GEMO group on bone metastases management:
      a special focus on external beam radiotherapy practice survey.
AB  - BACKGROUND AND PURPOSE: This study seeks to perform a survey of patterns of
      practice among the different physicians involved in the bone metastases
      management, with special focus on external beam radiotherapy (EBRT). METHODS AND
      MATERIALS: A questionnaire about bone metastases based on clinical cases and
      supplemented with general questions, including medical therapies, EBRT and
      metabolic radiotherapy strategies, surgery, and supportive care approaches, was
      sent to 4,706 French-speaking physicians in Belgium, France, Luxemburg, and
      Switzerland. RESULTS: Overall, 644 questionnaires were analyzed. Twenty-eight
      percent concerned the radiotherapy approach and were judged adequate to respond
      to the part dedicated to EBRT. Sixty-nine percent of physicians used a total dose
      irradiation of 30 Gy delivered in ten fractions. A large majority (75%) used two
      opposed fields prescribed at mid-depth (30%), or with non-equally weighted fields
      (45%). Seventy percent irradiated also above and below the concerned vertebra. A
      dosimetry planning treatment was done in 85% and high-energy megavoltage photons
      were used in 42%. Moreover, 54% physicians used short course radiotherapy in
      routine. CONCLUSIONS: Radiotherapy remains the mainstay of treatment of bone
      metastases, but there is substantial heterogeneity in clinical practice.
      Guidelines and treatment protocols are required to improve the treatment quality.

PMID- 20809196
TI  - Living in the hands of God. English Sunni e-fatwas on (non-)voluntary euthanasia
      and assisted suicide.
AB  - Ever since the start of the twentieth century, a growing interest and importance
      of studying fatwas can be noted, with a focus on Arabic printed fatwas (Wokoeck
      2009). The scholarly study of end-of-life ethics in these fatwas is a very recent
      feature, taking a first start in the 1980s (Anees 1984; Rispler-Chaim 1993).
      Since the past two decades, we have witnessed the emergence of a multitude of
      English fatwas that can easily be consulted through the Internet ('e-fatwas'),
      providing Muslims worldwide with a form of Islamic normative guidance on a huge
      variety of topics. Although English online fatwas do provide guidance for Muslims
      and Muslim minorities worldwide on a myriad of topics including end-of-life
      issues, they have hardly been studied. This study analyses Islamic views on (non
      )voluntary euthanasia and assisted suicide as expressed in English Sunni fatwas
      published on independent--i.e. not created by established organisations--Islamic
      websites. We use Tyan's definition of a fatwa to distinguish between fatwas and
      other types of texts offering Islamic guidance through the Internet. The study of
      e-fatwas is framed in the context of Bunt's typology of Cyber Islamic
      Environments (Bunt 2009) and in the framework of Roy's view on the virtual umma
      (Roy 2002). '(Non-)voluntary euthanasia and assisted suicide' are defined using
      Broeckaert's conceptual framework on treatment decisions at the end of life
      (Broeckaert 2008). We analysed 32 English Sunni e-fatwas. All of the e-fatwas
      discussed here firmly speak out against every form of active termination of life.
      They often bear the same structure, basing themselves solely on Quranic verses
      and prophetic traditions, leaving aside classical jurisprudential discussions on
      the subject. In this respect they share the characteristics central in Roy's
      typology of the fatwa in the virtual umma. On the level of content, they are in
      line with the international literature on Islamic end-of-life ethics. English
      Sunni e-fatwas make up an influential and therefore important developing body of
      Islamic orthodox normative authority on end-of-life ethics that is still open for
      further research.

PMID- 20809197
TI  - The role of aromatic side-chains in amyloid growth and membrane interaction of
      the islet amyloid polypeptide fragment LANFLVH.
AB  - Human islet amyloid polypeptide (hIAPP) is known to misfold and aggregate into
      amyloid deposits that may be found in pancreatic tissues of patients affected by
      type 2 diabetes. Recent studies have shown that the highly amyloidogenic peptide
      LANFLVH, corresponding the N-terminal 12-18 region of IAPP, does not induce
      membrane damage. Here we assess the role played by the aromatic residue Phe in
      driving both amyloid formation and membrane interaction of LANFLVH. To this aim,
      a set of variant heptapeptides in which the aromatic residue Phe has been
      substituted with a Leu and Ala is studied. Differential scanning calorimetry
      (DSC) and membrane-leakage experiments demonstrated that Phe substitution
      noticeably affects the peptide-induced changes in the thermotropic properties of
      the lipid bilayer but not its membrane damaging potential. Atomic force
      microscopy (AFM), ThT fluorescence and Congo red birefringence assays evidenced
      that the Phe residue is not required for fibrillogenesis, but it can influence
      the self-assembling kinetics. Molecular dynamics simulations have paralleled the
      outcome of the experimental trials also providing informative details about the
      structure of the different peptide assemblies. These results support a general
      theory suggesting that aromatic residues, although capable of affecting the self
      assembly kinetics of small peptides and peptide-membrane interactions, are not
      essential either for amyloid formation or membrane leakage, and indicate that
      other factors such as beta-sheet propensity, size and hydrophobicity of the side
      chain act synergistically to determine peptide properties.

PMID- 20809198
TI  - Contributions of studies on alcohol use disorders to understanding cerebellar
      function.
AB  - Neuropathological, neuropsychological, and neuroimaging studies of human
      alcoholism provide evidence for degradation of frontal, pontine, thalamic, and
      cerebellar brain sites and disturbed associated functions. Current studies using
      neuroimaging combined with examination of executive functions, traditionally
      considered the sole purview of the frontal lobes, have identified a role for the
      cerebellum serving as a compensatory processing adjunct to enable normal
      performance on challenging tasks tapping executive functions. This overview
      proposes that disruption of an executive frontocerebellar network is a major
      contributor to characteristic behaviors of alcoholism that, on the one hand,
      enable alcohol use disorders, and on the other hand, lead to compensation for
      dysfunctions in alcoholism traditionally considered frontally-based.

PMID- 20809199
TI  - Solving the mystery of the human cerebellum.
AB  - The mystery of the human cerebellum is this: Why did it enlarge so dramatically
      in the last million years of human evolution, concomitantly with the greater
      enlargement of the cerebral cortex? A solution to this mystery was proposed in
      the 20th century as a result of research by several groups of scientists who
      investigated the contributions of the cerebellum to the cerebral cortex. In
      contrast to the 19th century investigations, which were focused on the motor
      functions of the cerebellum, the focus of the subsequent investigations was
      expanded to include some mental functions because evidence was produced that the
      cerebellum contributes to cognition. It was proposed that the combination in the
      cerebellum of motor and mental capabilities enables the cerebellum to confer on
      humans some adaptive advantages of great value, and this ability would explain
      why the human cerebellum has continued to enlarge so dramatically. A valuable
      adaptive advantage that is included in the proposal is the possibility that the
      cerebellum couples the motor function of articulating speech to the mental
      function that selects the language to be spoken, thus helping to produce fluent
      human speech and language. The validity of this proposal about linguistic
      processing has not yet been verified. Therefore the mystery of cerebellar
      enlargement in humans is not yet solved and requires further research.

PMID- 20809201
TI  - Ring/marker chromosome derived from chromosome 7 in childhood acute
      megakaryoblastic leukemia with monosomy 7.
AB  - In some cases of childhood acute megakaryoblastic leukemia (AMKL), G-band
      analysis reveals supernumerary ring/marker chromosomes along with monosomy 7.
      However, their origin and relevance are poorly understood. We experienced three
      patients with AMKL, one of whom had Down's syndrome, whose blasts at the first
      visit exhibited both monosomy 7 and a ring/marker chromosome. For one case,
      precise molecular-cytogenetic techniques revealed that the ring chromosome was
      derived from a chromosome 7. It was strongly suggested that the ring chromosome
      was derived from a chromosome 7 in another case. The ring or one of the 2 marker
      chromosomes was derived from a chromosome 7 in the other case. All patients
      responded well to initial induction therapy. While it is not clear whether the
      ring/marker chromosome 7 affects the long-term prognosis of acute myeloid
      leukemia with monosomy 7, it may be of prognostic relevance to distinguish pure
      monosomy 7 from monosomy 7 with a ring/marker chromosome 7. For this purpose,
      conventional G-banding could be complemented with additional techniques such as
      spectral karyotyping or fluorescence in situ hybridization, which characterize
      the aberration in more detail. These methods may be useful for determining the
      optimal treatment and for elucidating the etiology of AMKL itself.

PMID- 20809200
TI  - Facial emotion recognition in autism spectrum disorders: a review of behavioral
      and neuroimaging studies.
AB  - Behavioral studies of facial emotion recognition (FER) in autism spectrum
      disorders (ASD) have yielded mixed results. Here we address demographic and
      experiment-related factors that may account for these inconsistent findings. We
      also discuss the possibility that compensatory mechanisms might enable some
      individuals with ASD to perform well on certain types of FER tasks in spite of
      atypical processing of the stimuli, and difficulties with real-life emotion
      recognition. Evidence for such mechanisms comes in part from eye-tracking,
      electrophysiological, and brain imaging studies, which often show abnormal eye
      gaze patterns, delayed event-related-potential components in response to face
      stimuli, and anomalous activity in emotion-processing circuitry in ASD, in spite
      of intact behavioral performance during FER tasks. We suggest that future studies
      of FER in ASD: 1) incorporate longitudinal (or cross-sectional) designs to
      examine the developmental trajectory of (or age-related changes in) FER in ASD
      and 2) employ behavioral and brain imaging paradigms that can identify and
      characterize compensatory mechanisms or atypical processing styles in these
      individuals.

PMID- 20809202
TI  - The role of FSH and TSH in bone loss and its clinical relevance.
AB  - Osteoporosis, a global health problem, is now frequently recognized to be
      secondary to alterations in the pituitary-bone axis. This review examines the
      current evidence for how dysregulation of the pituitary-bone axis leads to
      osteoporotic bone loss. Specifically, perimenopausal bone loss in the context of
      follicle-stimulating hormone action, and hyperthyroid bone loss in the context of
      thyroid-stimulating hormone action are explored. From the reviewed scientific
      findings, recommendations for early diagnosis and better clinical management of
      bone loss are made.

PMID- 20809203
TI  - Bone loss in diabetes: use of antidiabetic thiazolidinediones and secondary
      osteoporosis.
AB  - Clinical evidence indicates that bone status is affected in patients with type 2
      diabetes mellitus (T2DM). Regardless of normal or even high bone mineral density,
      T2DM patients have increased risk of fractures. One class of antidiabetic drugs,
      thiazolidinediones (TZDs), causes bone loss and further increases facture risk,
      placing TZDs in the category of drugs causing secondary osteoporosis. Risk
      factors for development of TZD-induced secondary osteoporosis are gender (women),
      age (elderly), and duration of treatment. TZDs exert their antidiabetic effects
      by activating peroxisome proliferator-activated receptor-gamma (PPAR-gamma)
      nuclear receptor, which controls glucose and fatty acid metabolism. In bone, PPAR
      gamma controls differentiation of cells of mesenchymal and hematopoietic
      lineages. PPAR-gamma activation with TZDs leads to unbalanced bone remodeling:
      bone resorption increases and bone formation decreases. Laboratory research
      evidence points toward a possible separation of unwanted effects of PPAR-gamma on
      bone from its beneficial antidiabetic effects by using selective PPAR-gamma
      modulators. This review also discusses potential pharmacologic means to protect
      bone from detrimental effects of clinically used TZDs (pioglitazone and
      rosiglitazone) by using combinational therapy with approved antiosteoporotic
      drugs, or by using lower doses of TZDs in combination with other antidiabetic
      therapy. We also suggest a possible orthopedic complication, not yet supported by
      clinical studies, of delayed fracture healing in T2DM patients on TZD therapy.

PMID- 20809204
TI  - Depression, selective serotonin reuptake inhibitors, and osteoporosis.
AB  - An increasing number of studies suggest an association between depression and
      osteoporosis. In a mouse model, depression induces bone loss, mediated by brain
      to-bone sympathetic signaling. Depression and bone antianabolic sympathetic tone
      are alleviated by increasing central serotonin (5-hydroxytryptamine, 5-HT)
      levels. However, selective serotonin reuptake inhibitors (SSRIs), the first-line
      antidepressants, increase extracellular 5-HT levels but have deleterious skeletal
      effects. The skeletal serotonergic system consists of 5-HT receptors and the 5-HT
      transporter (5-HTT) in osteoblasts and osteocytes. 5-HTT is a transmembrane
      protein targeted by SSRIs. 5-HT restrains osteoblastic activity, thus leading to
      bone loss. Apparently, the negative skeletal effects of the peripheral SSRI
      induced increase in 5-HT outweighs the skeletal benefits resulting from the
      enhanced central 5-HT antidepressant and antisympathetic activity. Overall, major
      depression appears as an important risk factor for osteoporosis. However,
      antidepressants, mainly SSRIs, should be evaluated in view of the causal
      relationship between depression and bone loss, and vis-a-vis their skeletal
      adverse effects. Patients with depressive disorders should undergo a routine
      skeletal evaluation and receive timely antiosteoporotic therapy, especially when
      SSRI treatment is prescribed.

PMID- 20809205
TI  - A phase I and pharmacokinetic study of liposomal vinorelbine in patients with
      advanced solid tumor.
AB  - PURPOSE: This phase I study was performed to determine the maximum tolerated dose
      (MTD) and dose-limiting toxicity (DLT) of an untargeted liposomal formulation of
      vinorelbine (NanoVNB(r)) and to characterize its plasma pharmacokinetics in
      patients with advanced solid tumors which were refractory to conventional
      treatment or without an effective treatment. PATIENTS & METHODS: The study
      incorporated an accelerated titration design. Twenty-two patients with various
      solid tumors were enrolled. NanoVNB((r)) was administered intravenously at doses
      of 2.2-23 mg/m(2) once every 14 days. Pharmacokinetic endpoints were evaluated in
      the first cycle. The safety profiles and anti-tumor effects of NanoVNB(r) were
      also determined. RESULTS: Skin rash was the DLT and the most common non
      hematological toxicity. The MTD was 18.5 mg/m(2). Drug-related grade 3-4
      hematological toxicities were infrequent. Compared with intravenous free
      vinorelbine, NanoVNB(r) showed a high C(max) and low plasma clearance. Of the 11
      patients completing at least 1 post-treatment tumor assessment, 5 had stable
      disease. No responders were noted. CONCLUSION: NanoVNB(r) was well tolerated and
      exhibited more favorable pharmacokinetic profiles than free vinorelbine. Based on
      dose-limiting skin toxicity, further evaluation of NanoVNB(r) starting from 18.5
      mg/m(2) as a single agent or in combination with other chemotherapeutic agents
      for vinorelbine-active malignancies is warranted.

PMID- 20809206
TI  - Expression of Nur77 induced by an n-butylidenephthalide derivative promotes
      apoptosis and inhibits cell growth in oral squamous cell carcinoma.
AB  - In spite of numerous advances, the 5-year survival rate for head and neck
      squamous cell cancer has remained largely stagnant and few new anti-tumor drugs
      have been developed. PCH4, a derivative of n-butylidenephthalide, has been
      investigated for its anti-tumor effects on oral squamous cell carcinoma (OSCC).
      The aim of this study was to investigate the anti-tumor mechanism of a potential
      target gene, Nur77, in OSCC cells, which can be induced by PCH4 treatment. Data
      show that PCH4 promoted Nur77 translocation from the nucleus to the cytoplasm and
      induced cell apoptosis in OSCC cells. When Nur77 translocation was blocked, the
      degree of tumor apoptosis caused by PCH4 was significantly inhibited (p < 0.05).
      Within the MAPK pathway, PCH4 only induced JNK phosphorylation. Furthermore,
      treatment with a JNK inhibitor significantly reduced PCH4-induced apoptosis (p <
      0.05) and decreased PCH4-induced Nur77 expression (p < 0.05). In a xenograft
      animal model, administration of PCH4 also showed anti-tumor effects. We have
      demonstrated that OSCC cells are sensitive to PCH4 and that Nur77 protein
      translocation from the nucleus to the cytoplasm might be associated with the
      induction of apoptosis by PCH4. These results indicate that PCH4 may serve as a
      potential anti-tumor drug for OSCC therapy.

PMID- 20809207
TI  - [11C]acetate PET/CT visualizes skeletal muscle exercise participation, impaired
      function, and recovery after hip arthroplasty; first results.
AB  - PURPOSE: Based on skeletal muscle acetate physiology we aimed studying muscle
      function after hip arthroplasty with [(11)C]acetate PET. PROCEDURES: Two male
      patients were investigated 3 and 12 weeks after hip arthroplasty with muscle
      [(11)C]acetate PET/CT performed at rest and exercise. Median muscle SUV(mean)
      were calculated on three non-consecutive transverse PET slices. RESULTS: The four
      exercise PET/CT showed, compared with rest, consistent increase in [(11)C]acetate
      uptake in active muscles contralateral to surgery. On the arthroplasty side most
      muscles showed symmetric activity increase under exercise both at 3 and 12 weeks
      after surgery, but four muscles showed only minor activity increase at 3 weeks.
      At 3 months, functional recovery of the latter four muscles was observed.
      CONCLUSION: Consistent increase in [(11)C]acetate uptake in healthy muscles under
      exercise compared with rest was observed by PET/CT. Transiently impaired muscle
      function 3 weeks after surgery recovered at 3 months. These first observations
      merit further investigation.

PMID- 20809208
TI  - A low molecular weight folate receptor targeted contrast agent for magnetic
      resonance tumor imaging.
AB  - PURPOSE: This study aims to develop a low molecular weight folate receptor (FR)
      contrast agent for MR tumor imaging. PROCEDURES: Gadolinium-tetraazacyclododecane
      tetraacetic acid (Gd.DOTA) was conjugated to folic acid to create Gd.DOTA.Folate.
      The efficacy of Gd.DOTA.Folate to bind FR was evaluated in vitro by inductively
      coupled mass spectrometry (ICP-MS) and in vivo by magnetic resonance imaging
      (MRI) tumor enhancement over 14 h, utilizing an overexpressing alpha-FR cell line
      (IGROV-1), compared to an alpha-FR-negative cell line (OVCAR-3). Gd.DOTA.Folate
      localization ex vivo was verified by laser ablation ICP-MS. RESULTS: ICP-MS
      confirmed Gd.DOTA.Folate uptake by IGROV-1 cells and competitive binding with
      free folic acid inhibited binding. IGROV-1 tumors showed an increase in R (1) at
      2 h, which increased significantly over 14 h post-Gd.DOTA.Folate with clear
      enhancement on MR images. This was not observed in controls. CONCLUSION: These
      data support the use of FR-targeted small molecular weight MRI contrast agents
      for tumor imaging in vivo.

PMID- 20809209
TI  - Development of high-throughput quantitative assays for glucose uptake in cancer
      cell lines.
AB  - PURPOSE: Metabolism, and especially glucose uptake, is a key quantitative cell
      trait that is closely linked to cancer initiation and progression. Therefore,
      developing high-throughput assays for measuring glucose uptake in cancer cells
      would be enviable for simultaneous comparisons of multiple cell lines and
      microenvironmental conditions. This study was designed with two specific aims in
      mind: the first was to develop and validate a high-throughput screening method
      for quantitative assessment of glucose uptake in "normal" and tumor cells using
      the fluorescent 2-deoxyglucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4
      yl)amino]-2-deoxyglucose (2-NBDG), and the second was to develop an image-based,
      quantitative, single-cell assay for measuring glucose uptake using the same probe
      to dissect the full spectrum of metabolic variability within populations of tumor
      cells in vitro in higher resolution. PROCEDURE: The kinetics of population-based
      glucose uptake was evaluated for MCF10A mammary epithelial and CA1d breast cancer
      cell lines, using 2-NBDG and a fluorometric microplate reader. Glucose uptake for
      the same cell lines was also examined at the single-cell level using high-content
      automated microscopy coupled with semi-automated cell-cytometric image analysis
      approaches. Statistical treatments were also implemented to analyze intra
      population variability. RESULTS: Our results demonstrate that the high-throughput
      fluorometric assay using 2-NBDG is a reliable method to assess population-level
      kinetics of glucose uptake in cell lines in vitro. Similarly, single-cell image
      based assays and analyses of 2-NBDG fluorescence proved an effective and accurate
      means for assessing glucose uptake, which revealed that breast tumor cell lines
      display intra-population variability that is modulated by growth conditions.
      CONCLUSIONS: These studies indicate that 2-NBDG can be used to aid in the high
      throughput analysis of the influence of chemotherapeutics on glucose uptake in
      cancer cells.

PMID- 20809210
TI  - Quantitating antibody uptake in vivo: conditional dependence on antigen
      expression levels.
AB  - PURPOSE: Antibodies form an important class of cancer therapeutics, and there is
      intense interest in using them for imaging applications in diagnosis and
      monitoring of cancer treatment. Despite the expanding body of knowledge
      describing pharmacokinetic and pharmacodynamic interactions of antibodies in
      vivo, discrepancies remain over the effect of antigen expression level on tumoral
      uptake with some reports indicating a relationship between uptake and expression
      and others showing no correlation. PROCEDURES: Using a cell line with high
      epithelial cell adhesion molecule expression and moderate epidermal growth factor
      receptor expression, fluorescent antibodies with similar plasma clearance were
      imaged in vivo. A mathematical model and mouse xenograft experiments were used to
      describe the effect of antigen expression on uptake of these high-affinity
      antibodies. RESULTS: As predicted by the theoretical model, under subsaturating
      conditions, uptake of the antibodies in such tumors is similar because
      localization of both probes is limited by delivery from the vasculature. In a
      separate experiment, when the tumor is saturated, the uptake becomes dependent on
      the number of available binding sites. In addition, targeting of small
      micrometastases is shown to be higher than larger vascularized tumors.
      CONCLUSIONS: These results are consistent with the prediction that high affinity
      antibody uptake is dependent on antigen expression levels for saturating doses
      and delivery for subsaturating doses. It is imperative for any probe to
      understand whether quantitative uptake is a measure of biomarker expression or
      transport to the region of interest. The data provide support for a predictive
      theoretical model of antibody uptake, enabling it to be used as a starting point
      for the design of more efficacious therapies and timely quantitative imaging
      probes.

PMID- 20809211
TI  - Phase-locked parallel movement of diaphragm and pelvic floor during breathing and
      coughing-a dynamic MRI investigation in healthy females.
AB  - INTRODUCTION AND HYPOTHESIS: the aim of this pilot study was to demonstrate
      physiological movements of the muscular walls surrounding the abdominal cavity
      during breathing and coughing in healthy nulliparous women by means of real-time
      dynamic magnetic resonance imaging (MRI). METHODS: eight volunteers underwent MRI
      measurements in a 1.5-T whole body MR-scanner. Coronal and sagittal slices were
      acquired simultaneously to assess respiratory-related cranio-caudal movement of
      diaphragm and pelvic floor (PF) and concomitant changes in horizontal abdominal
      diameter. RESULTS: respective mean amplitudes of cranio-caudal movement of the
      right and left diaphragmatic cupolae were 15 +/- 6 and 9 +/- 7 mm during quiet
      breathing; 32 +/- 15 and 28 +/- 16 mm during forceful breathing; and 32 +/- 13
      and 28 +/- 7 mm during coughing. Both diaphragm and PF moved caudally during
      inspiration and cranially during expiration. Abdominal diameter decreased in all
      eight women consistently during the expiration phase of breathing, and in five
      women during coughing. CONCLUSIONS: in healthy women, real-time dynamic MRI
      demonstrates parallel cranio-caudal movement of the diaphragm and the PF during
      breathing and coughing and synchronous changes in abdominal wall diameter.

PMID- 20809212
TI  - The developmental impact of prenatal stress, prenatal dexamethasone and postnatal
      social stress on physiology, behaviour and neuroanatomy of primate offspring:
      studies in rhesus macaque and common marmoset.
AB  - RATIONALE: Exposure of the immature mammalian brain to stress factors, including
      stress levels of glucocorticoids, either prenatally or postnatally, is regarded
      as a major regulatory factor in short- and long-term brain function and, in
      human, as a major aetiological factor in neuropsychiatric disorders. Experimental
      human studies are not feasible and animal studies are required to demonstrate
      causality and elucidate mechanisms. A number of studies have been conducted and
      reviewed in rodents but there are relatively few studies in primates. OBJECTIVES:
      Here we present an overview of our published studies and some original data on
      the effects of: (1) prenatal stress on hypothalamic-pituitary-adrenal (HPA)
      re/activity and hippocampus neuroanatomy in juvenile-adolescent rhesus macaques;
      (2) prenatal dexamethasone (DEX) on HPA activity, behaviour and prefrontal cortex
      neuroanatomy in infant-adolescent common marmosets; (3) postnatal daily parental
      separation stress on HPA re/activity, behaviour, sleep and hippocampus and
      prefrontal cortex neuroanatomy in infant-adolescent common marmoset. RESULTS:
      Prenatal stress increased basal cortisol levels and reduced neurogenesis in
      macaque. Prenatal DEX was without effect on HPA activity and reduced social play
      and skilled motor behaviour in marmoset. Postnatal social stress increased basal
      cortisol levels, reduced social play, increased awakening and reduced hippocampal
      glucocorticoid and mineralocorticoid receptor expression in marmoset.
      CONCLUSIONS: Perinatal stress-related environmental events exert short- and long
      term effects on HPA function, behaviour and brain status in rhesus macaque and
      common marmoset. The mechanisms mediating the enduring effects remain to be
      elucidated, with candidates including increased basal HPA function and epigenetic
      programming.

PMID- 20809213
TI  - A single dose of mirtazapine modulates neural responses to emotional faces in
      healthy people.
AB  - RATIONALE: Single-dose administration of selective serotonin and noradrenaline
      reuptake blockers has been shown to alter emotional processing in both behavioral
      and fMRI studies in healthy volunteers. Mirtazapine is a clinically established
      antidepressant with different pharmacological actions from monoamine reuptake
      inhibitors, involving blockade of noradrenaline alpha(2)-adrenoceptors and
      multiple 5-HT receptor subtypes. The aim of this study was to investigate the
      effect of a single dose of mirtazapine on the neural processing of emotional
      faces in healthy volunteers. METHODS: Twenty-eight participants were randomized
      to receive either a single dose of mirtazapine (15 mg) or placebo. Two hours
      later, participants underwent an fMRI scan, in which they classified fearful and
      happy faces on the basis of gender. Mood and subjective experience were also
      measured. RESULTS: Whole-brain analysis showed significant group * emotion
      interactions in a right amygdala-hippocampal region and left fronto-striatal
      cortex. Post hoc analyses revealed significantly reduced activation to fear and
      greater activation to happy faces in both regions under mirtazapine. CONCLUSIONS:
      Our findings indicate that a single dose of mirtazapine modulates neural activity
      to affective stimuli. Mirtazapine was found to decrease neural responses to fear
      and increase responses to happy facial expressions in regions implicated in the
      processing of emotional faces. These effects may be important for our
      understanding of the neural mechanisms of antidepressant action in anxiety and
      depression.

PMID- 20809214
TI  - Cytokine combination therapy with erythropoietin and granulocyte colony
      stimulating factor in a porcine model of acute myocardial infarction.
AB  - PURPOSE: Erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF)
      have generated interest as novel therapies after myocardial infarction (MI), but
      the effect of combination therapy has not been studied in the large animal model.
      We investigated the impact of prolonged combination therapy with EPO and GCSF on
      cardiac function, infarct size, and vascular density after MI in a porcine model.
      METHODS: MI was induced in pigs by a 90 min balloon occlusion of the left
      anterior descending coronary artery. 16 animals were treated with EPO+GCSF, or
      saline (control group). Cardiac function was assessed by echocardiography and
      pressure-volume measurements at baseline, 1 and 6 weeks post-MI. Histopathology
      was performed 6 weeks post-MI. RESULTS: At week 6, EPO+GCSF therapy stabilized
      left ventricular ejection fraction, (41 +/- 1% vs. 33 +/- 1%, p < 0.01) and
      improved diastolic function compared to the control group. Histopathology
      revealed increased areas of viable myocardium and vascular density in the
      EPO+GCSF therapy, compared to the control. Despite these encouraging results, in
      a historical analysis comparing combination therapy with monotherapy with EPO or
      GCSF, there were no significant additive benefits in the LVEF and volumes
      overtime using the combination therapy. CONCLUSION: Our findings indicate that
      EPO+GCSF combination therapy promotes stabilization of cardiac function after
      acute MI. However, combination therapy does not seem to be superior to
      monotherapy with either EPO or GCSF.

PMID- 20809215
TI  - Efficacy of simvastatin in reducing aortic dilatation in mouse models of
      abdominal aortic aneurysm.
AB  - PURPOSE: Currently there is no effective drug therapy for abdominal aortic
      aneurysm (AAA). The aim of this study was to assess the ability of simvastatin to
      inhibit aortic dilatation in two mouse models. METHODS: AAAs were induced in two
      mice strains predisposed to atherosclerosis. Firstly, 11 weeks old male
      apolipoprotein E deficient (ApoE(-/-)) mice were given vehicle control (n = 27)
      or simvastatin (50 mg/kg/d, n = 27) prior to being infused with angiotensin II (1
      MUg/kg/min) subcutaneously for 4 weeks. Secondly, 9 weeks old male low-density
      lipoprotein receptor deficient (LDLR(-/-)) mice were fed a high fat diet, then
      given vehicle control (n = 17) or simvastatin (50 mg/kg/d, n = 18) and from 14 to
      18 weeks of age infused with angiotensin II. Subsequently aortas were harvested,
      maximum suprarenal aortic diameter measured, aortic arch atheroma assessed by
      sudan IV staining and blood extracted to measure serum lipids. In the LDLR(-/-)
      mice the suprarenal aortic diameter was also measured by ultrasound prior to
      aortic harvesting. RESULTS: In ApoE(-/-) mice suprarenal aortic diameters were
      modestly smaller in animals receiving simvastatin without significant change
      despite reduction in macrophage infiltration. Aortic arch atheroma was
      substantially reduced in LDLR(-/-) mice receiving simvastatin with borderline
      significant reduction in suprarenal aortic diameters. Simvastatin did not
      favourably modify serum lipids in either mouse model. CONCLUSIONS: In this study
      involving two mouse models of AAA, simvastatin had limited efficacy in
      restricting aortic dilatation but substantial ability to reduce atheroma
      progression.

PMID- 20809216
TI  - Cardiovascular pharmacotherapy 2010: foreword.

PMID- 20809218
TI  - Pre-exposure prophylaxis state of the science: empirical analogies for research
      and implementation.
AB  - Pre-exposure prophylaxis (PrEP) has the potential to become a powerful biomedical
      approach to HIV prevention; however, its success depends on behavioral and social
      factors that may determine its appropriate use. This article is designed to
      facilitate interdisciplinary empirical analogies relevant to PrEP implementation,
      reviewing behavioral and social science findings that may provide lessons
      critical to the success of PrEP as a biomedical-behavioral prevention strategy.
      As we prepare for the dissemination of new biomedical approaches to HIV
      prevention, integrating the state of the science across disciplines may result in
      innovative strategies for implementation that can enhance their success.

PMID- 20809217
TI  - Value of PET-FDG in primary breast cancer based on histopathological and
      immunohistochemical prognostic factors.
AB  - BACKGROUND: The aim of the study was to analyze in breast tumors the correlation
      between [(18)F]fluorodeoxyglucose (FDG) uptake assessed by positron emission
      tomography (PET) and histopathological and immunohistochemical prognostic
      factors. METHODS: FDG-PET combined with computed tomography (CT) was performed
      before surgery in 45 women with biopsy-proven primary breast cancer. The
      standardized uptake value (SUV) was compared with histopathological findings
      after surgery. RESULTS: A positive relationship was found between SUV and
      histological grade (p < 0.0001), histological type (p = 0.001), tumor size (p <
      0.0435), estrogen receptor status (p < 0.0005), and progesterone receptor status
      (p = 0.002). FDG-PET/CT revealed unknown distant metastatic lesions in 2 of 12
      patients with triple-negative breast cancer. The sensitivity of FDG-PET/CT for
      detecting axillary lymph node metastases was, respectively, 21% and 100% for pN1
      and pN2 cases, whereas specificity was 100% for pN0. CONCLUSION: SUV, a
      preoperative and noninvasive metabolic parameter, correlates with other known
      prognostic factors in breast cancer. This study provides valuable insight into
      the usefulness of FDG-PET/CT for preoperative staging of patients with triple
      negative and poorly differentiated breast tumors but not for evaluating axillary
      lymph nodes and lobular carcinomas.

PMID- 20809220
TI  - Intestinal damage in enterohemorrhagic Escherichia coli infection.
AB  - Enterohemorrhagic Escherichia coli (EHEC) infection leads to marked intestinal
      injury. Sigmoid colon obtained from two children during EHEC infection exhibited
      abundant TUNEL-positive cells. To define which bacterial virulence factors
      contribute to intestinal injury the presence of Shiga toxin-2 (Stx2), intimin and
      the type III secretion system were correlated with symptoms and intestinal
      damage. C3H/HeN mice were inoculated with Stx2-producing (86-24) and non
      producing (87-23) E. coli O157:H7 strains and 86-24 mutants lacking eae, encoding
      intimin (strain UMD619) or escN regulating the expression of type III secretion
      effectors (strain CVD451). Severe symptoms developed in mice inoculated with 86
      24 and 87-23. Few mice inoculated with the mutant strains developed severe
      symptoms. Strain 86-24 exhibited higher fecal bacterial counts, followed by 87
      23, whereas strains UMD619 and CVD451 showed minimal fecal counts. More TUNEL
      positive cells were found in proximal and distal colons of mice inoculated with
      strain 86-24 compared with strains 87-23 and CVD451 (p <= 0.01) or UMD619 (p <
      0.05, proximal colon, p < 0.01, distal colon). The results show that strains 86
      24 and 87-23 exhibited better colonic persistence and more symptoms, presumably
      due to the presence of intimin and type III secretion effectors. Extensive
      intestinal mucosal cell death was related to the presence of Stx2.

PMID- 20809221
TI  - Measurement and prediction of enteric methane emission.
AB  - The greenhouse gas (GHG) emissions from the agricultural sector account for about
      25.5% of total global anthropogenic emission. While CO(2) receives the most
      attention as a factor relative to global warming, CH(4), N(2)O and
      chlorofluorocarbons (CFCs) also cause significant radiative forcing. With the
      relative global warming potential of 25 compared with CO(2), CH(4) is one of the
      most important GHGs. This article reviews the prediction models, estimation
      methodology and strategies for reducing enteric CH(4) emissions. Emission of
      CH(4) in ruminants differs among developed and developing countries, depending on
      factors like animal species, breed, pH of rumen fluid, ratio of
      acetate:propionate, methanogen population, composition of diet and amount of
      concentrate fed. Among the ruminant animals, cattle contribute the most towards
      the greenhouse effect through methane emission followed by sheep, goats and
      buffalos, respectively. The estimated CH(4) emission rate per cattle, buffaloe,
      sheep and goat in developed countries are 150.7, 137, 21.9 and 13.7
      (g/animal/day) respectively. However, the estimated rates in developing countries
      are significantly lower at 95.9 and 13.7 (g/animal/day) per cattle and sheep,
      respectively. There exists a strong interest in developing new and improving the
      existing CH(4) prediction models to identify mitigation strategies for reducing
      the overall CH(4) emissions. A synthesis of the available literature suggests
      that the mechanistic models are superior to empirical models in accurately
      predicting the CH(4) emission from dairy farms. The latest development in
      prediction model is the integrated farm system model which is a process-based
      whole-farm simulation technique. Several techniques are used to quantify enteric
      CH(4) emissions starting from whole animal chambers to sulfur hexafluoride (SF6)
      tracer techniques. The latest technology developed to estimate CH(4) more
      accurately is the micrometeorological mass difference technique. Because the
      conditions under which animals are managed vary greatly by country, CH(4)
      emissions reduction strategies must be tailored to country-specific
      circumstances. Strategies that are cost effective, improve productivity, and have
      limited potential negative effects on livestock production hold a greater chance
      of being adopted by producers. It is also important to evaluate CH(4) mitigation
      strategies in terms of the total GHG budget and to consider the economics of
      various strategies. Although reductions in GHG emissions from livestock
      industries are seen as high priorities, strategies for reducing emissions should
      not reduce the economic viability of enterprises.

PMID- 20809222
TI  - The hygiene hypothesis revisited: role of materno-fetal interactions.
AB  - For 20 years, the hygiene hypothesis has dominated attempts to explain the
      increasing prevalence of allergic disease. A causal link between maternal innate
      immune response during pregnancy and disease protection in the offspring was
      recently demonstrated. Central to this was a systemically diffused signal that
      downregulated Toll-like receptor expression in placental tissues. Herein we
      develop the hypothesis that maternal systemic regulatory mechanisms operational
      during pregnancy could impact allergic disease risk of the offspring, depending
      on the type of inflammatory response from which they originate. Classic microbial
      derived, mild, subacute inflammation provides a protective signal, whereas
      allergic inflammation provides a negative one. Mild, subacute inflammation of
      pregnant women leads to systemically diffused signals manifest in the gestation
      associated tissues and by the fetus and newborn as a dampened inflammatory
      response. The converse is true if the mother has allergic inflammation during
      pregnancy. In both cases, these impact on development of the airways and of
      balanced immune function at birth and in early postnatal life. Thus, we seem to
      be at the dawn of a new incarnation of the hygiene hypothesis in which the
      pregnant woman's inflammatory response is crucial to determining the child's
      likelihood of developing allergic disease.

PMID- 20809223
TI  - Oseltamivir treatment for acute otitis media in children with influenza.

PMID- 20809225
TI  - The addition of rituximab to fludarabine and cyclophosphamide improves
      progression-free survival in patients with previously treated chronic lymphocytic
      leukemia.

PMID- 20809224
TI  - Targeted signal transduction therapies in myeloid malignancies.
AB  - The myeloid malignancies include the myeloproliferative neoplasms (MPN) including
      chronic myeloid leukemia (CML), and acute myeloid leukemia (AML). A growing body
      of evidence documents that these diseases are caused by genetic mutations that
      constitutively activate tyrosine kinases. They include the BCR/ABL in CML, the
      V617F JAK2 in Philadelphia chromosome-negative MPN, and the Flt3 ITD and TKD
      mutations in AML. Trials of the ABL kinase inhibitor, imatinib, have
      revolutionized the treatment of CML, and there are ongoing studies with other
      kinase inhibitors in MPN and AML. Here we review results of recent studies with
      first-generation JAK2 inhibitors in the treatment of MPN and second-generation
      ABL and Flt3 inhibitors in CML and AML, respectively. It is becoming apparent
      that although these kinase mutations have similar effects in vitro, each of the
      diseases has unique features that alter the use of kinase inhibitors in the
      clinic.

PMID- 20809226
TI  - Biological active metabolite cyclo (L-Trp-L-Phe) produced by South China Sea
      sponge Holoxea sp. associated fungus Aspergillus versicolor strain TS08.
AB  - Sponge-associated fungi represent the single most prolific source of novel
      natural products from marine fungi. Cyclo (L-Trp-L-Phe) exhibits biological
      functions such as plant growth regulation, moderate cytotoxicity and thus has the
      application potential in pharmaceutical and agricultural biotechnologies. In this
      study, a fungal strain TS08 was isolated from sponge Holoxea sp. in the South
      China Sea and identified as A. versicolor according to its 18S rRNA gene and
      morphological, physiological, and biochemical characteristics. Meanwhile, cyclo
      (L-Trp-L-Phe) was found to be produced by A. versicolor strain TS08 mainly in the
      exponential growth phase. The highest yield of cyclo (L-Trp-L-Phe), 13.24 mg/g
      (per crude extract of EtOAc), 2.51% of cell dry weigh, was obtained on the tenth
      day of the fungal cultivation. It was the first time to find the biological
      active cyclo (L-Trp-L-Phe) in sponge-associated microorganism.

PMID- 20809227
TI  - Phylogeny can be used to make useful predictions of soil-to-plant transfer
      factors for radionuclides.
AB  - Soil-to-plant transfer of radionuclides can be related to plant evolutionary
      history (phylogeny). For some species and radionuclides the effect is significant
      enough to be useful in predicting Transfer Factors (TFs). Here a Residual Maximum
      Likelihood (REML)-based mixed model and a recent plant phylogeny are used to
      compile data on soil-to-plant transfer of radionuclides and to show how the
      phylogeny can be used to fill gaps in TFs. Using published data, generic means
      for TFs are used to anchor the data from REML modelling and hence predict TFs for
      important groups of plants. Radionuclides of Cs are used as an example. With a
      generic soil-to-plant TF of 0.07, TFs of 0.035 and 0.085 are predicted for
      monocot and eudicot gaps, respectively. Also demonstrated is how the known
      effects of soil conditions can be predicted across plant groups-predicted Cs TFs
      for gap-filling across all flowering plants are calculated for sandy loams with
      and without waterlogging. Predictions of TFs for Sr, Co, Cl and Ru are also
      given. Overall, the results show that general predictions of TFs based on
      phylogeny are possible-a significant contribution to gap filling for TFs.

PMID- 20809228
TI  - Effects of Tai Chi on adiponectin and glucose homeostasis in individuals with
      cardiovascular risk factors.
AB  - The aim of this study was to evaluate the acute effect of a single bout of Tai
      Chi (TC) exercise on adiponectin and glucose homeostasis in individuals with
      cardiovascular risk factors. Twenty-six individuals (mean age 60.2 years) with at
      least one cardiovascular risk factor who had been practicing Yang's style TC
      exercise for at least 3 months were recruited from a regional hospital in Taiwan.
      A one-group repeated measured quasi-experimental design was used. Participants
      completed a 60-min Yang's style TC exercise routine including warm up, stretching
      exercises, and TC followed by a 30-min resting period. After a 1-week washout
      period, the same group of participants underwent a control condition in which
      they were instructed to remain seated for 90 min at the study location. Blood
      samples were collected both before and after the TC intervention or the sitting
      condition. The difference between pre-post measurements for adiponectin was 0.58
      +/- 1.42 MUg/ml in the TC trial and -0.46 +/- 0.99 MUg/ml in the sitting trial.
      The differences between the two trials were statistically significant (P =
      0.004). The changes from pretrial to posttrial were significantly greater for
      glycerol (P < 0.001), cholesterol (P = 0.046), and LDL-C (P = 0.038) in the TC
      trial compared with those in the sitting trial. Conversely, the changes were
      significantly lesser for HOMA-IR (P = 0.004), log (HOMA-IR) (P = 0.001), and
      glucose (P = 0.003) in TC trial compared with those in the sitting trial. In
      conclusion, a single bout of TC exercise had a significant positive effect on
      blood adiponectin concentrations in individuals with cardiovascular risk factors.

PMID- 20809229
TI  - The effect of acute effort on EEG in healthy young and elderly subjects.
AB  - The effects of physical exercise on mental health have been extensively
      investigated, mainly in older people. Recent studies have looked into the acute
      effect of exercise on the brain using standardized low-resolution brain
      electromagnetic tomography (sLORETA). We assessed EEG power and mood changes
      after 20 min of aerobic exercise in elderly (N = 10) and young (N = 19) healthy
      individuals. Both groups showed improvement in total mood disturbance (TMD) post
      exercise (young: P = 0.03; elderly: P = 0.02). Only the young group showed
      significant improvement in anger (P = 0.05) and vigor (P = 0.006). Comparison pre
      versus post-exercise for each group separately revealed significant changes in
      the young group (an increase in alpha, beta-1 and beta-2 activity in Brodmann
      areas 24, 33 and 23, respectively). However, the elderly group did not show
      significant changes. An inverse correlation was found between alpha asymmetry and
      STAI (rs = -0.50; P = 0.029) in the young group. On the other hand, a significant
      correlation between beta-1 activity and TMD was observed in the elderly group (rs
      = 0.67; P = 0.045). We conclude that acute exercise can have distinct effects on
      brain activity and mood variables in young individuals when compared with elderly
      adults. However, additional studies are necessary to further investigate the role
      of exercise intensity in these results.

PMID- 20809230
TI  - Comprehensive evaluation of a single-stage submaximal treadmill walking protocol
      in healthy, middle-aged women.
AB  - Cardiorespiratory fitness is an independent predictor of cardiovascular events in
      women; however, maximal oxygen consumption (VO(2max)) protocols are not always
      feasible. The Evaluation of Physical Activity Measures in Middle-Aged Women Study
      was a 6-week study designed to evaluate six physical activity (PA) measures in
      women, aged 45-65 years. We investigated the Ebbeling submaximal treadmill
      (EbbTM) protocol's ability to reflect an active lifestyle in 66 women [median
      (IQR) age, 51.0 (48.0, 56.5) years]. Participants were screened using ACSM and
      AHA guidelines and classified as moderate or low cardiovascular risk. VO(2max)
      was estimated using the EbbTM in all participants (TEST1). Moderate risk women
      repeated the EbbTM (TEST2) while low risk completed a maximal treadmill test.
      Intraclass correlation coefficients (ICC) and minimal detectable change (MDC(90))
      score were calculated to examine reliability. Spearman rank order or Pearson
      product-moment correlation coefficients were used to determine the association
      between estimated VO(2max) and physical fitness and activity measures. Estimated
      VO(2max) from the EbbTM protocol had excellent reproducibility [ICC = 0.95 (95%
      CI: 0.89, 0.98) and MDC(90) was 1.62 mL kg(-1) min(-1). The EbbTM protocol was
      associated with measured VO(2max) (rho = 0.48; p = 0.01) and was positively
      correlated with moderate- (rho = 0.32; p = 0.02), vigorous- (rho = 0.47; p =
      0.0005) and moderate-to-vigorous-intensity PA (rho = 0.36; p = 0.009), pedometer
      steps (rho = 0.41; p = 0.002) and inversely correlated with waist circumference
      (rho = -0.58; p < 0.0001), body fat (rho = -0.55; p < 0.0001), and right leg
      endurance (rho = -0.41; p = 0.003). The EbbTM protocol was shown to be reliable
      and associated with objective measures of fitness and PA in healthy, middle-aged
      women.

PMID- 20809231
TI  - Effect of contrast water therapy duration on recovery of cycling performance: a
      dose-response study.
AB  - This study investigated whether contrast water therapy (CWT) has a dose-response
      effect on recovery from high-intensity cycling. Eleven trained male cyclists
      completed four trials, each commencing with a 75-min cycling protocol containing
      six sets of five 15-s sprints and three 5-min time-trials in thermoneutral
      conditions. Ten minutes post-exercise, participants performed one of four
      recovery protocols: CWT for 6 min (CWT6), 12 min (CWT12), or 18 min (CWT18)
      duration, or a seated rest control trial. The CWT commenced in hot water (38.4 +/
      0.6 degrees C) and alternated between hot and cold water (14.6 +/- 0.3 degrees
      C) every minute with a 5-s changeover. The cycling protocol was repeated 2 h
      after completion of exercise bout one. Prior to exercise bout two, core
      temperature was lower in CWT12 (-0.19 +/- 0.14 degrees C, mean +/- 90% CL) and
      CWT18 (-0.21 +/- 0.10 degrees C) than control. Compared with control, CWT6
      substantially improved time-trial (1.5 +/- 2.1%) and sprint performance (3.0 +/-
      3.1%), and CWT12 substantially improved sprint total work (4.3 +/- 3.4%) and peak
      power (2.7 +/- 3.8%) in exercise bout two. All CWT conditions generally improved
      thermal sensation, whole body fatigue and muscle soreness compared with control,
      but no differences existed between conditions in heart rate or rating of
      perceived exertion. In conclusion, CWT duration did not have a dose-response
      effect on recovery from high-intensity cycling; however, CWT for up to 12 min
      assisted recovery of cycling performance.

PMID- 20809232
TI  - HSPA1A is upregulated in periodontal ligament at early stage of tooth movement in
      rats.
AB  - Heat shock proteins (HSPs) are molecular chaperones that maintain intracellular
      protein homeostasis and ensure survival of cells. Continuous orthodontic force on
      the tooth is considered to be a type of physical stress loaded to the periodontal
      ligament (PDL). However, little is known about the role of HSPs during tooth
      movement. This study was performed to examine the expression of HSPs in the PDL
      during tooth movement using laser microdissection, microarray analysis, real-time
      RT-PCR and immunohistochemistry. Gene expression of HSPA1A in the pressure zone
      of the PDL was higher during 6 h of tooth movement than in the control group.
      Expression of HSPA1A decreased with time. HSPA1A was also detected in the
      pressure zone of the PDL at the protein level 24 h after the initial tissue
      change. These results strongly suggest that expression of HSPA1A in the PDL
      during early stages of tooth movement is a critical factor for tissue reaction.

PMID- 20809233
TI  - Lamellar body ultrastructure revisited: high-pressure freezing and cryo-electron
      microscopy of vitreous sections.
AB  - Lamellar bodies are the storage sites for lung surfactant within type II alveolar
      epithelial cells. The structure-function models of lamellar bodies are based on
      microscopic analyses of chemically fixed tissue. Despite available alternative
      fixation methods that are less prone to artifacts, such as cryofixation by high
      pressure freezing, the nature of the lung, being mostly air filled, makes it
      difficult to take advantage of these improved methods. In this paper, we propose
      a new approach and show for the first time the ultrastructure of intracellular
      lamellar bodies based on cryo-electron microscopy of vitreous sections in the
      range of nanometer resolution. Thus, unspoiled by chemical fixation, dehydration
      and contrasting agents, a close to native structure is revealed. Our approach
      uses perfluorocarbon to substitute the air in the alveoli. Lung tissue was
      subsequently high-pressure frozen, cryosectioned and observed in a cryo-electron
      microscope. The lamellar bodies clearly show a tight lamellar morphology. The
      periodicity of these lamellae was 7.3 nm. Lamellar bifurcations were observed in
      our cryosections. The technical approach described in this paper allows the
      examination of the native cellular ultrastructure of the surfactant system under
      near in vivo conditions, and therefore opens up prospectives for scrutinizing
      various theories of lamellar body biogenesis, exocytosis and recycling.

PMID- 20809234
TI  - Advances in pharmacologic modulation of nitric oxide in hypertension.
AB  - A number of structural and functional mechanisms have been identified in the
      pathogenesis of hypertensive vascular disease, each of which requires effective
      therapy to reduce global cardiovascular risk. Hypertension, together with other
      cardiovascular risk factors, promotes endothelial dysfunction as evidenced by
      decreased nitric oxide (NO) release and reduced vascular responsiveness to normal
      vasodilatory stimuli. In addition, the mechanical forces inherent in hypertension
      activate neurohormonal mechanisms, including the renin-angiotensin system, which
      modulate vessel wall structure and function. Antihypertensive drugs may have
      class-specific hemodynamic and physiologic effects that attenuate these vascular
      disease processes. Pharmacologic approaches that enhance endothelial NO
      bioavailability have been shown to restore vasodilation while reducing clinical
      events. These agents improve NO bioavailability by increasing endogenous
      production through enzymatic mechanisms or by promoting the direct release of NO
      by its redox congeners in a spontaneous fashion. In this article, we review the
      basic mechanisms of endothelial dysfunction along with the use and comparative
      therapeutic benefits of various pharmacologic interventions, with particular
      emphasis on antihypertensive agents.

PMID- 20809235
TI  - The omega-3 index: clinical utility for therapeutic intervention.
AB  - Red blood cell levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid
      (DHA) are a reflection of tissue levels and are determined by a complex interplay
      of metabolism and nutrition. Low levels of EPA+DHA in erythrocytes are associated
      with increased risk for sudden cardiac death. If levels of EPA+DHA in
      erythrocytes are determined using a strictly defined and standardized method,
      then the clinical significance of differing levels (previously defined in major
      research studies using this methodology) may be understood and applied in patient
      care. The Omega-3 Index, which is the EPA+DHA content of erythrocytes expressed
      as a percent of total identified fatty acids, was originally suggested as a
      marker of increased risk for death from coronary heart disease, but it can also
      be viewed as an actual risk factor, playing a pathophysiologic role in the
      disease. Optimal levels appear to be 8% or greater. At this stage of its
      development, the Omega-3 Index appears to fulfill many of the requirements for
      both a risk marker and a risk factor. Using the Omega-3 Index in the design of
      clinical studies might allow for a more efficient use of research resources.

PMID- 20809236
TI  - The role of renin-angiotensin agents in altering the natural history of type 2
      diabetes mellitus.
AB  - Type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease
      (CVD) morbidity and mortality worldwide. Renin-angiotensin system (RAS) blockers
      have been indispensable in diminishing the macrovascular and microvascular
      complications of diabetes. In addition, cumulative evidence from retrospective
      studies pointed toward a beneficial effect of RAS agents in preventing the
      development and progression of T2DM. This disease-modifying potential of RAS
      blockers has been substantiated by recent prospective trials. Contemporary
      concepts regarding the natural history of T2DM and the pathophysiologic processes
      involved have increased our understanding of the mechanisms underlying the
      therapeutic potential of these agents in diabetes management. In addition to
      their established roles in the primary prevention of CVD in patients with
      diabetes, RAS blockers might be considered a suitable therapeutic choice for
      preventing the development of frank diabetes in high-risk patients.

PMID- 20809237
TI  - Effects of the compounds MV8608 and MV8612 obtained from Mandevilla velutina in
      the model of hemorrhagic cystitis induced by cyclophosphamide in rats.
AB  - Hemorrhagic cystitis (HC) is a common side effect observed in patients under
      chemotherapy with cyclophosphamide (CYP). The urotoxic side effects of CYP are
      attributed to the metabolic compound acrolein, and can be partially prevented by
      the uroprotector agent 2-mercaptoethene sulfate (Mesna). The present study
      analyzed the anti-inflammatory and the antinociceptive effects of compounds
      MV8608 and MV8612 obtained from Mandevilla velutina in the rat model of CYP
      induced HC. Male Wistar rats were used (six to eight per group, 220-250 g). HC
      was induced by a single administration of CYP (100 mg/kg, ip). Three behavioral
      parameters--breathing rate, closing of the eyes, and specific posture--were used
      as nociception indexes, and scored at different time intervals (15-180 min) after
      cystitis induction. As inflammatory parameters, hemorrhage presence, edema
      formation, and bladder weight were determined at 24 h after CYP administration.
      The neutrophil migration was assessed by means of myeloperoxidase (MPO activity),
      4 h after cystitis induction. As expected, Mesna treatment was able to reduce in
      a significant manner all the inflammatory and the nociceptive parameters induced
      by CYP. Of note, the administration of MV8608 significantly inhibited the
      hemorrhage formation and the neutrophil recruitment, while the MV8612 treatment
      markedly reduced the bladder weight, without interfering with neutrophil influx.
      Interestingly, the treatment with either MV8608 or MV8612 markedly reduced the
      nociceptive responses. The present results clearly indicate that MV8608 and
      MV8612 might represent important alternatives to prevent side effects, especially
      the nociception, following chemotherapy with CYP.

PMID- 20809238
TI  - Identification of trace-amine-associated receptors (TAAR) in the rat aorta and
      their role in vasoconstriction by beta-phenylethylamine.
AB  - Trace amines including tyramine and beta-phenylethylamine (beta-PEA) increase
      blood pressure and cause vasoconstriction which is attributed to indirect
      sympathomimetic actions. However, there is evidence that they may also have non
      sympathomimetic mechanisms. This study examined whether beta-PEA causes
      vasoconstriction of rat aorta by a sympathomimetic action or through the recently
      described trace-amine-associated receptors (TAAR). Concentration-response curves
      (CRCs) for beta-PEA were constructed either cumulatively or non-cumulatively in
      rat isolated aortic rings. TAAR-1 and TAAR-4 protein expression was determined in
      rat aorta by Western blotting and TAAR-1 mRNA by reverse transcriptase polymerase
      chain reaction (RT-PCR). beta-PEA caused concentration-related constriction of
      rat aorta. The contractions were unaffected by endothelium removal or the nitric
      oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME, 100
      MUM) or the cyclooxygenase inhibitor, indomethacin (10 MUM). Non-cumulative CRCs
      showed greater contractions and sensitivity to beta-PEA than cumulative. The
      alpha(1)-adrenoceptor antagonist, prazosin, failed to inhibit either curve. The
      beta-adrenoceptor antagonist, propranolol, the adrenergic neuronal transport
      inhibitor, cocaine, and the monoamine oxidase inhibitor, pargyline, also failed
      to alter the CRC. In the combined presence of prazosin, cocaine, pargyline, and
      the selective beta(2)-adrenoceptor antagonist, ICI-118,551, the trace amine
      contractile potency order was tryptamine > beta-PEA > octopamine > D: 
      amphetamine > tyramine. Western blotting and RT-PCR revealed the presence of TAAR
      1 in rat aorta, but TAAR-4 was poorly expressed. Vasoconstriction of rat aorta by
      beta-PEA appears not to be an indirect sympathomimetic action. The presence of
      TAAR-1 suggests that vasoconstriction may be via these receptors; however, the
      potency order differed from that reported for transfected cells expressing rat
      TAAR-1.

PMID- 20809239
TI  - The anti-platelet effects of apocynin in mice are not mediated by inhibition of
      NADPH oxidase activity.
AB  - Apocynin, or a (myelo)peroxidase-derived product thereof, is a powerful inhibitor
      of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Apocynin has also
      been shown to prevent aggregation of platelets in response to agonists such as
      collagen and thrombin. The aims of this study were to establish whether NADPH
      oxidase activity is required for aggregation of murine platelets to collagen and
      other agonists and whether the anti-aggregatory effects of apocynin are due to an
      inhibitory action against this enzyme. Washed platelets were isolated from male
      C57BL6 (wild-type), Nox2-deficient (Nox2(-/y )), and p47phox-deficient (p47phox(
      /-)) mice for assessment of aggregation and NADPH oxidase subunit (Nox2, p47phox)
      expression. Collagen and U46619 elicited aggregation of murine platelets, and
      these responses were inhibited by apocynin at concentrations >=100 MUM. By
      contrast, aggregations to a direct protein kinase C activator, phorbol-12,13
      dibutyrate, were insensitive to apocynin. Immunoblotting of platelet protein
      homogenates from wild-type mice with anti-Nox2 or p47phox antibodies revealed
      strong bands at 58 and 50 kDa, respectively. While expression of these
      immunoreactive bands was greatly diminished in platelets from Nox2(-/y ) and
      p47phox(-/-) mice, collagen still elicited aggregations that were similar to
      those observed in platelets from wild-types. Moreover, apocynin was an equally
      effective inhibitor of aggregation in platelets from all three mouse strains. In
      conclusion, these data suggest that NADPH oxidase-derived reactive oxygen species
      play no role in the aggregation response of washed murine platelets to collagen.
      Thus, our observation that apocynin is a powerful inhibitor of platelet
      aggregation raises further questions about the selectivity of this drug as an
      NADPH oxidase inhibitor.

PMID- 20809240
TI  - Pseudomonas putida bacteremia in adult patients: five case reports and a review
      of the literature.
AB  - Pseudomonas putida belongs to the fluorescent group of Pseudomonas species, a
      group of opportunistic pathogens that primarily cause nosocomial infections.
      However, few cases of P. putida bacteremia in adult patients have been reported.
      We report five cases of P. putida bacteremia in adult patients and review 23
      previously reported cases. Our five patients consisted of three cases of catheter
      related bloodstream infection (CRBSI), one case of indwelling biliary drainage
      tube-related cholangitis, and one case of cholecystitis. Many of the 23
      previously reported cases also included CRBSI. Of the clinical backgrounds, in
      all 28 reported cases including ours, 24 (85.7%) were immunocompromised. Of the
      clinical management, in CRBSI, devices were removed in almost all cases (92.9%).
      Antibiotic susceptibility data of our five cases and another previous case showed
      that patients with bacteremia had a high susceptibility of P. putida to anti
      pseudomonal beta-lactams. The prognosis for bacteremia with P. putida was good,
      as 26 (92.9%) of the total 28 cases were cured.

PMID- 20809241
TI  - Analysis of risk factors for surgical-site infections in 276 oral cancer
      surgeries with microvascular free-flap reconstructions at a single university
      hospital.
AB  - The purpose of this study was to elucidate the risk factors for surgical-site
      infection (SSI) in oral cancer surgery with microvascular free-flap
      reconstructions and to propose appropriate SSI prevention. There were 276
      patients who underwent oral cancer surgery with microvascular free-flap
      reconstructions at the Department of Oral and Maxillo-facial Surgery of Tokai
      University Hospital. The following variables were assessed as risk factors for
      SSIs: preoperative variables, including age, sex, body mass index, American
      Society of Anesthesiologist's (ASA) score, debilitating comorbidities, smoking,
      alcohol consumption, and Union Internationale Contre le Cancer Tumor Node
      Metastasis (UICC-TNM) classification; and operative variables, including duration
      of surgery, amount of blood loss, quantity of blood transfusion, tracheostomy,
      area of neck dissection, and previous chemotherapy. Statistical analysis was
      conducted to determine whether these factors constitute risks for SSI. Total
      overall SSI rate was 40.6% (112/276). When the occurrence of SSI was compared
      with the variables, ASA score (P=0.036), T stage (P=0.013), duration of surgery
      (P<0.001), blood loss (P=0.001), blood transfusion (P=0.01), and area of neck
      dissection (P=0.009) showed statistical significance. Analysis of these variables
      with a logistic regression model yielded ASA score and duration of surgery as
      significant factors. There was a tendency for blood loss and duration of surgery
      to increase in patients with a high T stage. A high T stage not only broadens the
      resection area and increases surgical invasiveness, it also increases
      susceptibility to dead space after microvascular reconstruction for oral cancer.
      Particular care in treating the wound should be taken in surgical patients with
      high T-stage scores. The occurrence of SSI is of particular concern in oral
      cancer surgery in patients with high ASA scores.

PMID- 20809242
TI  - Giant pedunculated leiomyoma of the vulva in full-term pregnancy: is spontaneous
      vaginal delivery possible?

PMID- 20809243
TI  - Switch performance in peripherally and centrally triggered saccades.
AB  - A common hypothesis is that the switch cost measured when switching between
      prosaccades and antisaccades mainly reflects the inhibition of the saccadic
      system after the execution of an antisaccade, which requires the inhibition of a
      gaze response. The present study further tested this hypothesis by comparing
      switch performance between peripherally triggered saccades and centrally
      triggered saccades with the latter type of saccades not requiring inhibition of a
      gaze response. For peripherally triggered saccades, a switch cost was present for
      prosaccades but not for antisaccades. For centrally triggered saccades, a switch
      cost was present both for prosaccades and for antisaccades. The difference
      between both saccade tasks further supports the hypothesis that the switch
      performance observed for peripherally triggered saccades is related to the
      inhibition of a gaze response that is required when executing a peripherally
      triggered antisaccade and the persisting inhibition in the saccadic system this
      entails. Furthermore, the switch costs observed for centrally triggered saccades
      indicate that more general processes besides the persisting inhibition in the
      saccadic system, such as reconfiguration and interference control, also
      contribute to the switch performance in saccades.

PMID- 20809244
TI  - Sensory-motor equivalence: manual aiming in C6 tetraplegics following
      musculotendinous transfer surgery at the elbow.
AB  - Cervical spinal lesions at C6 result in paralysis of the triceps brachii while
      leaving deltoid and elbow flexor function intact. We examined the spatial
      temporal characteristics of goal-directed aiming movements performed by C6
      tetraplegics who had undergone musculotendinous transfer surgery in which the
      posterior deltoid replaces the triceps as the elbow extensor. On some trials,
      liquid crystal goggles were used to eliminate vision of the limb and target upon
      movement initiation. Although tetraplegic participants achieved the same degree
      of movement accuracy/consistency as control participants, their movement times
      were longer regardless of whether the movements were made away from (elbow
      extension) or towards the body (elbow flexion). Longer movement times were
      related to lower peak velocities, and not the symmetry of the aiming profiles.
      The tetraplegic participants were no more dependent on visual feedback for limb
      regulation than control participants. Although the characteristics of the
      movement trajectories were surprisingly similar, in both vision conditions,
      tetraplegics required more real and proportional time to reduce spatial
      variability in the limb's trajectory for elbow extensions. Our results indicate
      that the sensorimotor system is adaptable and that the representations governing
      limb control are not muscle specific.

PMID- 20809245
TI  - Variable osseous anatomy of costal surface of scapula and its implications in
      relation to snapping scapula syndrome.
AB  - BACKGROUND: Variation in normal anatomy of costal surface of scapula may disrupt
      smooth scapulothoracic movements and may cause snapping scapula. The aim of this
      study was to assess variable anatomy of costal surface of scapula and its role in
      etiopathogenesis of snapping scapula syndrome. MATERIALS AND METHODS:
      Superomedial angle, depth of costal surface, forward angulation of root of
      coracoid process and thickness of superior and inferior angles of 92 dry intact
      adult scapulae of unknown sex were studied. RESULTS: Superomedial angle ranged
      from 124 degrees  to 162 degrees  (144.34 degrees  +/- 9.09 degrees ). The
      forward angulation of root of coracoid process ranged from 120 degrees  to 160
      degrees  (141.60 degrees  +/- 6.53 degrees ). Depth of costal surface at the
      level of root of spine varied widely between 10.5 and 26.7 mm (16.73 +/- 3.367
      mm). Thickness of superior and inferior angles measured 3.34 +/- 0.87 and 6.71 +/
      1.18 mm, respectively. Forwardly bent rhinoceros-horn-like projection at the
      lateral border of scapula was seen in 2.17% of specimens. CONCLUSION: Variation
      in anatomy of costal surface of scapula observed in this study may be clinically
      significant with respect to snapping scapula syndrome.

PMID- 20809246
TI  - Using a modified nasotracheal tube to prevent nasal ala pressure sore during
      prolonged nasotracheal intubation.
AB  - Nasotracheal tube induced nasal ala pressure sores or necrosis during prolonged
      nasotracheal intubation have been reported, and it is a serious but preventable
      complication. Here we introduce a modified nasotracheal tube to prevent this
      complication. This modified nasotracheal tube is composed of two parts, an oral
      endotracheal tube and a proximal part of a preformed nasotracheal tube, which are
      linked by a connector. The use of this modified nasotracheal tube can prevent
      nasal ala pressure sores during prolonged nasotracheal intubation.

PMID- 20809247
TI  - Medical errors: the importance of the bullet's blunt end.

PMID- 20809248
TI  - A case of soft tissue metastasis from glioblastoma and review of the literature.
AB  - Despite recent advances, glioblastoma (GBM) remains incurable but is typically
      characterized by local tumor recurrence in the brain. Soft tissue metastases from
      GBM are extremely rare, with only eight reported cases in the literature. It has
      been postulated that this type of metastases rarely occurs due to inability of
      tumor cells to survive outside the brain milieu, physical barriers preventing
      tumor spread, and/or early patient death from this aggressive tumor. Here we
      present another case of soft tissue metastases that occurred in a young woman
      with GBM and review the previous literature.

PMID- 20809249
TI  - Fractionated radiotherapy for intracranial meningiomas.
AB  - Fractionated external beam radiotherapy (EBRT) has multiple roles in the
      management of intracranial meningiomas. In multiple series post-operative EBRT
      has shown improved progression-free survival following subtotal resection and a
      reduction in long-term failures following an apparent gross total resection. In
      the definitive setting, the use of EBRT has increased as the growing utilization
      of neuro-imaging for various conditions identifies skull-based lesions which are
      not easily resectable. Optic nerve sheath meningiomas represent a classic example
      of the use of definitive EBRT, given the frequent visual sequelae of surgery or
      observation. EBRT planning is highly individualized and requires a detailed
      understanding of tumor grade, adjacent radiosensitive structures such as the
      anterior optic apparatus, and radiographic characteristics of the tumor such as
      hyperostosis.

PMID- 20809250
TI  - Modern meningioma imaging techniques.
AB  - Steady improvements in imaging modalities have enabled a new realm of
      capabilities in the identification and assessment of meningiomas. The cross
      sectional imaging modalities, MRI and CT, have improved in resolution and
      fidelity. These modalites now provide not only improved structural information
      but also insights into functional behavior. MRI has, in particular, proven to
      have powerful capabilities in evaluating meningiomas because of the ability to
      assess soft tissue characteristics such as diffusion and vascular supply
      information, such as perfusion. Recent investigational advances have also been
      made using a combination of X-ray fluoroscopy for selective catheterization
      followed by MR perfusion measurement performed with intra-arterial injection of
      contrast. Together all these modalities provide the radiographer with powerful
      capabilities for evaluating meningiomas.

PMID- 20809252
TI  - Performance evaluation of medical records departments by analytical hierarchy
      process (AHP) approach in the selected hospitals in Isfahan : medical records
      dep. & AHP.
AB  - Medical Records Department (MRD) is an important unit for evaluating and planning
      of care services. The goal of this study is evaluating the performance of the
      Medical Records Departments (MRDs) of the selected hospitals in Isfahan, Iran by
      using Analytical Hierarchy Process (AHP). This was an analytic of cross-sectional
      study that was done in spring 2008 in Isfahan, Iran. The statistical population
      consisted of MRDs of Alzahra, Kashani and Khorshid Hospitals in Isfahan. Data
      were collected by forms and through brainstorm technique. To analyze and perform
      AHP, Expert Choice software was used by researchers. Results were showed
      archiving unit has received the largest importance weight with respect to
      information management. However, on customer aspect admission unit has received
      the largest weight. Ordering weights of Medical Records Departments' Alzahra,
      Kashani and Khorshid Hospitals in Isfahan were with 0.394, 0.342 and 0.264
      respectively. It is useful for managers to allocate and prioritize resources
      according to AHP technique for ranking at the Medical Records Departments.

PMID- 20809251
TI  - Pathological classification and molecular genetics of meningiomas.
AB  - Meningiomas are extremely common adult brain tumors originating from meningeal
      coverings of the brain and spinal cord. While most are slowly growing Word Health
      organization (WHO) grade I tumors, rare variants (clear cell, chordoid,
      papillary, and rhabdoid), as well as brain invasive (WHO grade II), atypical (WHO
      grade II), and anaplastic (WHO grade III) meningiomas are considerably more
      aggressive. This review summarizes the histopathological and genetic features of
      meningiomas, including differential diagnosis, pitfalls, and grading challenges.
      Early stages of meningioma tumorigenesis are closely linked to inactivation of
      one or more members of the 4.1 superfamily, including the neurofibromatosis type
      2 (NF2) and 4.1B (DAL-1) genes, which interact with the 14-3-3 protein family.
      Other chromosome 22q genes implicated include BAM22, BCR (breakpoint cluster
      region), and TIMP-1, the last of which is implicated in higher-grade meningiomas.
      Atypical meningiomas also commonly show chromosomal losses of 1p, 6q, 10, 14q,
      and 18q, as well as multiple chromosomal gains. While most relevant genes remain
      unknown, two chromosome 14q candidates (MEG3 and NDRG2) have recently been
      identified. In addition to alterations of CDKN2A, p14(ARF), and CDKN2B tumor
      suppressor genes on 9p21, a contribution of the wingless (wnt) pathway with
      alterations of the E-cadherin and beta-catenin proteins, as well as alterations
      of the hedgehog signaling pathway have been implicated in anaplastic meningiomas.
      The integration of histopathological appearance, complex genetic/genomic data,
      and outcome will likely result in the identification of clinically distinct
      meningioma subgroups, which in turn can facilitate the development of targeted
      therapeutic strategies.

PMID- 20809253
TI  - Evaluation of kidney transplantation programmes using system simulation.
AB  - In the case of kidney transplantations, there is always a serious imbalance
      between the number of kidneys donated for transplantation and the number of
      persons wishing to receive a transplant. This not only affects the quality of
      life of those unable to obtain a transplant, but it also has important
      repercussions on the treatment of End Stage Renal Disease (ESRD) by
      transplantation and dialysis. Also there are a number of ways in which the kidney
      transplantation can be achieved, such as the cadaveric kidney transplantation,
      live donor kidney transplantation, kidney paired donation and list exchange. A
      simulation study of all the referred programmes is performed using simulation
      models developed for each programme to obtain the better estimate of the average
      waiting time of a patient per year. With the estimates given by the simulation
      models, the best serving programme for each blood type patient is selected,
      declared and recommended.

PMID- 20809254
TI  - PI3K-dependent host cell actin rearrangements are required for Cronobacter
      sakazakii invasion of human brain microvascular endothelial cells.
AB  - Cronobacter sakazakii (C. sakazakii) is an opportunistic pathogen that can cause
      neonatal sepsis and meningitis. The mechanism involved in the pathogenesis of C.
      sakazakii meningitis remains largely unknown. Previous studies indicated that
      bacterial invasion of brain microvascular endothelial cells is required for
      penetration into the central nervous system. In this study, we found that C.
      sakazakii invasion of human brain microvascular endothelial cells (HBMEC) was
      significantly inhibited by cytochalasin D, a disrupting agent of actin
      microfilaments. Disassembly of actin stress fibers and cortical actin fibers was
      observed in HBMEC infected with C. sakazakii. C. sakazakii infection leads to
      increased Akt phosphorylation in HBMEC, which was blocked by treatment with PI3K
      inhibitors. Meanwhile, PI3K and Akt inhibitors significantly inhibited C.
      sakazakii invasion of HBMEC. Our further results illustrated that the C.
      sakazakii-induced Akt activation and C. sakazakii invasion were attenuated in
      HBMEC transfected with dominant-negative PI3K (Deltap110). More importantly, the
      actin filaments rearrangements in HBMEC induced by C. sakazakii were effectively
      blocked by PI3K inhibitors treatment and transfection with Deltap110. Taken
      together, our findings demonstrated that PI3K-mediated actin rearrangements are
      required for C. sakazakii invasion of HBMEC.

PMID- 20809255
TI  - Liver stem/progenitor cells in the canals of Hering: cellular origin of
      hepatocellular carcinoma with bile duct tumor thrombi?
AB  - It is generally believed that the invasion of hepatocellular carcinoma (HCC) into
      the biliary tree ultimately leads to the formation of bile duct tumor thrombi
      (BDTT). However, recent studies revealed that primary tumor might be small, even
      undetectable, and there was no histopathologic evidence of direct tumor invasion
      into bile duct wall in some patients. During the last decade, efforts on stem
      cell biology may shed light on the pathogenesis of BDTT. Presently, accumulating
      evidence supports the following notions: (1) the canals of Hering (CoH) are the
      most likely origin of liver stem/progenitor cells (LSPCs) in adult livers; (2)
      similar signalling pathways may regulate self-renewal in LSPCs and liver cancer
      cells, and a substantial proportion of liver tumors may often originate from the
      transformation of LSPCs; and (3) liver cancer contains rare cells with stem cell
      like properties, which could derive from malignant transformation of LSPCs.
      Herein, we propose that HCC with BDTT, especially with small or undetectable
      primary lesion and/or no histopathologic evidence for bile duct invasion, might
      arise from LSPCs residing in the CoH and, possibly, some primary lesions are
      formed firstly within the intrahepatic biliary tree. When "tumor thrombi" extends
      mainly along bile duct, there might be "BDTT" alone; when it invades into
      surrounding parenchyma, there might often be small "primary tumor" with "BDTT".
      If this holds true, the putative type may be a particular subset of HCC, and most
      importantly it would facilitate our understanding of stem-cell origin of HCC.

PMID- 20809256
TI  - Cord blood stem cells for hematopoietic transplantation.
AB  - Cord blood (CB) is an important alternative source of hematopoietic stem cells
      (HSCs) for transplantation today. The principal drawbacks of cord blood
      transplantation are the limited number of hematopoietic stem cells and a long
      time to engraftment. Several promising approaches for engraftment enhancement are
      under intensive investigation. Such are transplantation with two cord blood
      units, co transplantation of cord blood and haploidentical HSCs and different
      methods for expansion of cord blood hematopoietic stem cells. In addition there
      are several ways for improving of homing of HSCs such as co- infusion of CB
      hematopoietic stem cells and mesenchymal stem cells, administration of
      parathyroid hormone (PTH), intra- bone transplantation and targeting the
      CXCR4/SDF1 system. These strategies are expected to increase the availability of
      transplantation to adults, for whom the chance to find a cord blood suitable for
      a single unit transplant is small. Recent advances in elucidation of the
      molecular mechanisms responsible for the proliferation and self-renewal of
      hematopoietic stem cells may bring further improvement of the outcomes of cord
      blood transplantation. This review summarizes the recent progress in the field of
      cord blood derived hematopoietic stem cells. It presents the strategies applied
      and points out directions for the future.

PMID- 20809257
TI  - An inhibitor of arachidonate 5-lipoxygenase, Nordy, induces differentiation and
      inhibits self-renewal of glioma stem-like cells.
AB  - Recent progress in cancer biology indicates that eradication of cancer stem cells
      (CSCs) is essential for more effective cancer therapy. Unfortunately, cancer stem
      cells such as glioma stem-like cells (GSLCs) are often resistant to either radio-
      or chemotherapy. Therefore, screening and development for novel therapeutic
      modalities against CSCs has been an important emerging field in cancer research.
      In this study, we report that a synthetic dl-nordihydroguaiaretic acid compound
      (dl-NDGA or "Nordy"), inhibited self-renewal and induced differentiation of GSLCs
      in vitro and in vivo. We found that Nordy inhibited an enzyme known to be
      involved in leukemia stem cell and leukemia progression, Alox-5, and attenuated
      the growth of GSLCs in vitro. Nordy reduced the GSLC pool through a decrease in
      the CD133(+) population and abrogated clonogenicity. Nordy appeared to exert its
      effect via astrocytic differentiation by up-regulation of GFAP and down
      regulation of stemness related genes, rather than by inducing apoptosis of GSLCs.
      The growth inhibition of xenografted glioma by Nordy was more long-lasting
      compared with that of the akylating agent BCNU, which exhibited significant
      relapse on drug discontinuation resulting from an enrichment of GSLCs. Meanwhile,
      transient exposure to Nordy reduced tumorigenecity of GSLCs and induced
      differentiation of the xenografts. Taken together, we have identified Alox-5 as a
      novel target in GSLCs and its inhibition with Nordy exhibits therapeutic
      implications through inducing GSLC differentiation.

PMID- 20809258
TI  - A continuous mapping of sleep states through association of EEG with a mesoscale
      cortical model.
AB  - Here we show that a mathematical model of the human sleep cycle can be used to
      obtain a detailed description of electroencephalogram (EEG) sleep stages, and we
      discuss how this analysis may aid in the prediction and prevention of seizures
      during sleep. The association between EEG data and the cortical model is found
      via locally linear embedding (LLE), a method of dimensionality reduction. We
      first show that LLE can distinguish between traditional sleep stages when applied
      to EEG data. It reliably separates REM and non-REM sleep and maps the EEG data to
      a low-dimensional output space where the sleep state changes smoothly over time.
      We also incorporate the concept of strongly connected components and use this as
      a method of automatic outlier rejection for EEG data. Then, by using LLE on a
      hybrid data set containing both sleep EEG and signals generated from the
      mesoscale cortical model, we quantify the relationship between the data and the
      mathematical model. This enables us to take any sample of sleep EEG data and
      associate it with a position among the continuous range of sleep states provided
      by the model; we can thus infer a trajectory of states as the subject sleeps.
      Lastly, we show that this method gives consistent results for various subjects
      over a full night of sleep and can be done in real time.

PMID- 20809260
TI  - Anti-cancer effects of celecoxib on nasopharyngeal carcinoma HNE-1 cells
      expressing COX-2 oncoprotein.
AB  - Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor with antitumor and
      antiangiogenic activities. To investigate the effects of celecoxib on
      nasopharyngeal carcinoma (NPC), HNE-1 cells were treated with celecoxib at
      various concentrations. MTT assay, migration assay and invasion assay were
      performed to observe the inhibitory activity of celecoxib on HNE-1 cells.
      Additionally, VEGF-A expression and radiation survival of NPC cell were also
      examined after treatment with celecoxib. Celecoxib treatment presented an anti
      proliferation function in a time and dose-dependent manner on HNE-1 cells which
      highly express COX-2 protein. Celecoxib also displayed an obvious inhibitory
      activity on invasive capacity of NPC cells. Moreover, the celecoxib's effects to
      suppress VEGF-A expression and enhance radiosensitivity were detected in HNE-1
      cells. These findings implicate that application of celecoxib may be an effective
      strategy for NPC therapy.

PMID- 20809259
TI  - Moderate GSK-3beta inhibition improves neovascular architecture, reduces vascular
      leakage, and reduces retinal hypoxia in a model of ischemic retinopathy.
AB  - In ischemic retinopathies, unrelieved hypoxia induces the formation of
      architecturally abnormal, leaky blood vessels that damage retina and ultimately
      can cause blindness. Because these newly formed blood vessels are functionally
      defective, they fail to alleviate underlying hypoxia, resulting in more
      pathological neovascularization and more damage to retina. With an established
      model of ischemic retinopathy, we investigated inhibition of glycogen synthase
      kinase-3beta (GSK-3beta) as a means for improving the architecture and
      functionality of pathological blood vessels in retina. In vitro, hypoxia
      increased GSK-3beta activity in retinal endothelial cells, reduced beta-catenin,
      and correspondingly impaired integrity of cell/cell junctions. Conversely, GSK
      3beta inhibitors restored beta-catenin, improved cell/cell junctions, and
      enhanced the formation of capillary cords in three-dimensional collagen matrix.
      In vivo, GSK-3beta inhibitors, at appropriately moderate doses, strongly reduced
      abnormal vascular tufts, reduced abnormal vascular leakage, and improved vascular
      coverage and perfusion during the proliferative phase of ischemia-driven retinal
      neovascularization. Most importantly, these improvements in neovasculature were
      accompanied by marked reduction in retinal hypoxia, relative to controls. Thus,
      GSK-3beta inhibitors offer a promising strategy for alleviating retinal hypoxia
      by correcting key vascular defects typically associated with ischemia-driven
      neovascularization.

PMID- 20809261
TI  - Comparison of viable cell concentration estimation methods for a mammalian cell
      cultivation process.
AB  - Various mechanistic and black-box models were applied for on-line estimations of
      viable cell concentrations in fed-batch cultivation processes for CHO cells. Data
      from six fed-batch cultivation experiments were used to identify the underlying
      models and further six independent data sets were used to determine the
      performance of the estimators. The performances were quantified by means of the
      root mean square error (RMSE) between the estimates and the corresponding off
      line measured validation data sets. It is shown that even simple techniques based
      on empirical and linear model approaches provide a fairly good on-line estimation
      performance. Best results with respect to the validation data sets were obtained
      with hybrid models, multivariate linear regression technique and support vector
      regression. Hybrid models provide additional important information about the
      specific cellular growth rates during the cultivation.

PMID- 20809263
TI  - Early-onset sensorineural hearing loss in Lassa fever.
AB  - Lassa fever (LF) is a viral hemorrhagic disease which affects one-fourth to two
      million people annually with the fatality rate of about 10,000. It is associated
      with sensorineural hearing loss (SNHL) usually at the convalescent stage.
      Recently, cases of SNHL at the acute phase have been reported. This study was
      done to further investigate the incidence and features of SNHL in acute phase of
      LF. It is a prospective case-control study of LF patients seen with acute SNHL
      conducted between July 2007 and April 2009 at Irrua Specialist Teaching Hospital
      Nigeria. The diagnosis of acute LF was based on the clinical features and
      detection of IgM antibodies and/or positive Lassa virus-specific reverse
      transcriptase-polymerase chain reaction using primers S36+ and LVS 339 while SNHL
      was diagnosed clinically and confirmed with PTA and speech discrimination tests.
      Patients with other acute febrile illnesses were used as control. Statistical
      analysis was done using SPSS version 11 and Fisher's exact test while level of
      significance was set at p < 0.05. Out of the 37 confirmed cases of LF, 5 (13.5%)
      and none (0%) of the control developed early-onset SNHL (p = 0.03). Forty percent
      of the cases studied had negative IgM. The audiograms showed involvement at all
      frequency groups with pure tone average 65-85 dB and the speech discrimination 20
      40%. The overall case fatality rate was 27.0%, and for early SNHL cases 60.0% (p
      > 0.05). The incidence of SNHL in LF infection is about 13.5% and could be a
      reflection of a worse disease process. There is possibility of direct viral
      invasion aside immunological reaction as a causative mechanism.

PMID- 20809262
TI  - BRCA1 and BRCA2 families and the risk of skin cancer.
AB  - BRCA1 and BRCA2 mutation carriers have elevated risks of breast and ovarian
      cancers. The risks for cancers at other sites remain unclear. Melanoma has been
      associated with BRCA2 mutations in some studies, however, few surveys have
      included non-melanoma skin cancer. We followed 2729 women with a BRCA1 or BRCA2
      mutation for an average of 5.0 years. These women were asked to report new cases
      of cancer diagnosed in themselves or in their family. The risks of skin cancer
      were compared for probands with BRCA1 and BRCA2 mutations. Of 1779 women with a
      BRCA1 mutation, 29 developed skin cancer in the follow-up period (1.6%). Of the
      950 women with a BRCA2 mutation, 28 developed skin cancer (3.0%) (OR = 1.83 for
      BRCA2 versus BRCA1; 95% CI 1.08-3.10; P = 0.02). The odds ratio for basal cell
      carcinoma was higher (OR = 3.8; 95% CI 1.5-9.4; P = 0.002). BRCA2 mutation
      carriers are at increased risk for skin cancer, compared with BRCA1 carriers, in
      particular for basal cell carcinoma.

PMID- 20809264
TI  - CO(2) gas exchange across the human tympanic membrane is not appreciably affected
      by pathology.
AB  - Past in vivo studies in humans showed that the tympanic membrane (TM) is
      permeable to physiological gases. Animal studies show that transTM CO(2)
      conductance is increased by TM pathology. The objective of the study was to
      determine if transTM CO(2) exchange in humans is affected by atrophic and
      sclerotic pathologies. The study used an ear canal (EC) probe (ECP) constructed
      from a custom-fitted acrylic body, a glass capillary tube enclosing an oil
      meniscus to maintain ambient ECP + EC pressure and a silica glass microtube
      linked to a mass spectrometer (MS) for measuring gas composition that was
      hermetically sealed within the ear canal of the test ear. ECP + EC volume was
      measured and gas samples taken at 10 min intervals for 1 h. The fractional CO(2)
      pressure measured in the ECP + EC for each sample was regressed on time and the
      slope of the function multiplied by the ECP + EC volume and divided by the
      estimated transTM CO(2) gradient at the start of the experiment to yield transTM
      CO(2) conductance (microL/min/Pa). Data were complete for 15 normal, 13 sclerotic
      and 9 atrophic TMs. The average (+std) transTM CO(2) conductances were 1.76 * 10(
      4) + 7.27 * 10(-5), 2.26 * 10(-4) + 1.5 * 10(-4) and 2.36 * 10(-4) + 1.14 * 10(
      4) microL/min/Pa/TM for the normal, sclerotic and atrophic TMs, respectively. A
      pairwise comparison of data for the normal and atrophic TMs under the directional
      hypothesis of a greater CO(2) exchange rate for thinner TMs approached
      statistical significance (P = 0.07). A similar pairwise comparison for the
      sclerotic and normal TMs did not approach statistical significance (P = 0.28).
      The effect of TM pathologies on CO(2) conductance was limited.

PMID- 20809266
TI  - Relationship between inflammatory reaction and ischemic injury of caudate-putamen
      in rats: inflammatory reaction and brain ischemia.
AB  - Inflammatory response after middle cerebral artery occlusion (MCAO) has been a
      focus of research recently, but the effect of inflammatory cells on ischemic
      neurons remains unclear. In order to study the effect of the inflammatory
      reaction on brain ischemic injury, we observed the morphology, number and
      distribution of CD3-, CD8-, ED1- and ED2-positive cells systematically in the
      caudate-putamen of rats in a MCAO model. The present results show that all four
      types of inflammatory cells first infiltrated the ischemic penumbra and then
      migrated into the center of the ischemic area, but the morphological changes and
      infiltration processes differed significantly; the infiltration of CD3- and CD8
      positive cells into the ischemic area started at 3 days postischemia, and their
      number peaked at 1 week; however, although ED1- and ED2-positive cells were also
      observed at 3 days after ischemia, they reached their maximum number at 2 and 4
      weeks, respectively. Moreover, ED1-and ED2-positive cells showed evident
      hyperplasia and hypertrophy in morphology. Our results also showed that the
      response of CD3-, CD8-, ED1- and ED2-positive cells in the ischemic area and the
      pathological changes in ischemic brain tissue could be inhibited by cyclosporine
      A. The results suggest that the infiltration and reaction of inflammatory cells
      are involved in the pathological process of ischemic brain injury.

PMID- 20809267
TI  - Frequent consumption of selenium-enriched chicken meat by adults causes weight
      loss and maintains their antioxidant status.
AB  - To assess the effects of a moderately high-protein intake on the body
      composition, biochemical, and antioxidant status parameters in young adults
      depending on either selenium- (Se) or non-enriched chicken consumption. The
      volunteers (n = 24) that completed the 10-week nutritional intervention were
      distributed in two parallel groups and randomly assigned to follow an isocaloric
      diet with moderately high content in protein (30% energy), either with the
      consumption of four 200 g portions/week of Se- or non-enriched chicken breasts.
      Blood samples were taken at the beginning and at the end of the study and body
      composition was monitored during the trial. There was a significant reduction in
      weight, accompanying a decrease on fat mass in both groups, while fat-free mass
      remained unchanged during the 10 weeks of intervention, without differences
      between both dietary groups. Selenium blood levels and plasma glutathione
      peroxidase activity, as well as lipid, glucose, and selected inflammation
      biomarkers remained stable during the intervention period in both dietary groups.
      Frequent chicken consumption, within a controlled diet with a moderately high
      content in protein, produced a slight but statistically significant weight
      reduction mainly due to the loss of fat mass. An extra Se supplementation (22
      MUg/day) in the Se-enriched chicken breast did not affect tachyphylactic
      antioxidant status of the participants neither inflammatory-related markers after
      weight loss.

PMID- 20809268
TI  - Titanium, sinusitis, and the yellow nail syndrome.
AB  - Yellow nail syndrome is characterized by nail changes, respiratory disorders, and
      lymphedema. In a yellow nail patient with a skeletal titanium implant and with
      gold in her teeth, we found high levels of titanium in nail clippings. This study
      aims to examine the possible role of titanium in the genesis of the yellow nail
      syndrome. Nail clippings from patients with one or more features of the yellow
      nail syndrome were analyzed by energy dispersive X-ray fluorescence. Titanium was
      regularly found in finger nails in patients but not in control subjects. Visible
      nail changes were present in only half of the patients. Sinusitis with postnasal
      drip and cough was the most common complaint. The dominant source of titanium
      ions was titanium implants in the teeth or elsewhere. The titanium ions were
      released through the galvanic action of dental gold or amalgam or through the
      oxidative action of fluorides. In other patients the titanium was derived from
      titanium dioxide in drugs and confectionary. Stopping galvanic release of
      titanium ions or canceling exposure to titanium dioxide led to recovery. In one
      patient with a titanium implant, the symptoms recurred after renewed exposure to
      titanium. Yellow nail syndrome is caused by titanium.

PMID- 20809269
TI  - A model for calcium permeation into small intestine.
AB  - An in vitro model was used to simulate the intestinal permeation of calcium ions
      depending on the type of salt (carbonate, fumarate, citrate, or gluconate), its
      concentration (1.0, 2.5, 5.0, or 10 mM/l), and pH (1.3, 4.2, 6.2, or 7.5). To
      simulate the conditions for calcium permeation in a patient in a fasting state,
      the solutions were placed in contact with segments of small intestine of pig:
      stomach, duodenum, jejunum, and ileum. The percent permeation, its rate, and half
      time were measured in each case. In all cases, the maximum permeation was seen at
      1 mM concentration, depending on pH: 100% for carbonate at pH 1.3; 82% for
      fumarate, pH 6.2; 79.5% for citrate at pH 4.2, and 81% for gluconate at pH 7.4.
      The maximum rate of permeation (% h(-1)) was also observed at 1 mM: 2.16 for
      carbonate at pH 1.3, 0.29 for fumarate at pH 6.2, 0.26 for citrate at pH 4.2, and
      0.28 for gluconate at pH 7.4. The shortest half-time permeation (t (1/2), h) for
      1 mM solutions depended also on pH (in parentheses): carbonate 0.3 (1.3),
      fumarate 2.4 (6.2), citrate 2.6 (4.2), and gluconate 2.5 (7.4). The results
      suggest that calcium carbonate and citrate can be recommended to patients with
      normal gastric acidity and hyperacidity while fumarate and gluconate to patients
      with hypoacidity.

PMID- 20809270
TI  - The electrostatic interactions between nano-TiO(2) and trypsin inhibit the enzyme
      activity and change the secondary structure of trypsin.
AB  - In this work, the interaction between nano-TiO(2) and trypsin was investigated,
      and the mechanisms of the interaction were explored by the methods of UV-vis
      detection, circular dichroism (CD), and fluorescence. The results clearly
      demonstrated that nano-TiO(2) had an inhibitory effect on the enzyme activity.
      The activity was decreased to 64% of the untreated trypsin in the presence of 300
      MUg/ml nano-TiO(2). UV spectrometry proved that nano-TiO(2) had a strong physical
      absorption effect on trypsin, and the CD spectra revealed that the secondary
      structure of trypsin was partly destroyed while bound together with nano-TiO(2).
      The ratio of alpha-helix increased from 7.9% to 12.8% in the presence of 100
      MUg/ml TiO(2) while the ratio of beta-sheet decreased from 48.7% to 36.4%.
      Furthermore, the fluorescence spectrometry indicated that nano-TiO(2) could
      quench the intrinsic fluorescence of trypsin through static quenching. Meanwhile,
      the binding constant was calculated to be 1, and the process of binding of
      trypsin on nano-TiO(2) was a spontaneous molecular interaction procedure in which
      electrostatic interaction plays a major role. Our study was to provide a useful
      approach for evaluating the health risk of nanomaterials on level of proteins.

PMID- 20809271
TI  - Influence of copper, iron, zinc and fe (3) (+) haemoglobin levels on the
      etiopathogenesis of chronic calcific pancreatitis--a study in patients with
      pancreatitis.
AB  - Chronic pancreatitis is a serious condition associated with severe abdominal
      pain, and a significant percentage of patients progresses to irreversible
      calcification in pancreas. The present study evaluates the degree to which the
      levels of trace elements, copper, iron, selenium, zinc and haemoglobin-Fe(3+), in
      blood, serum and pancreas have any role to play in the calcification process
      associated with fibrosis in pancreas. Twenty-seven calcific (CCP) and 23 non
      calcific chronic pancreatitis (CP) patients and equal number of age- and sex
      matched normal volunteers (50) were enrolled in the study. Surgically removed
      pancreatic tissue and blood samples were analysed for copper, iron, selenium,
      zinc, protein, collagen and lipid peroxidation products in terms of
      malondialdehyde, protein carbonyls, glutathione, methemoglobin, methemoglobin
      reductase and ceruloplasmin activity levels. We could find that the pancreatic
      tissue levels of copper, iron, protein and collagen contents were significantly
      elevated in CCP patients when compared to CP patients. Serum levels of copper,
      free ionic copper and iron were also elevated in CCP patients. The serum and the
      pancreatic tissue level of zinc and selenium showed a significant decrease in CCP
      patients. The level of methemoglobin was elevated more significantly with the
      concomitant decline in the activity of methemoglobin reductase. There was a
      positive correlation between the pancreatic level of copper and iron with the
      collagen and protein levels. The results of the present study revealed that the
      levels of copper and iron, the pro-oxidants and zinc and selenium may influence
      calcification process in CCP patients. Hypoxia-related tissue injury due to the
      formation of oxidised haemoglobin may also contribute to the pathogenesis of
      calcification in pancreas.

PMID- 20809272
TI  - Plasma zinc, copper, and serum thyroid hormones and insulin levels after zinc
      supplementation followed by placebo in competitive athletes.
AB  - Intense physical activity is associated with biological adaptations involving
      hormones and trace elements. Zinc supplementation may affect plasma copper
      concentration, thyroid-stimulating hormone (TSH), thyroid hormones, insulin, and
      glucose homeostasis, but data in athletes are scarce. The aim of this study was
      to evaluate in competitive athletes (cyclists, n = 7, 32 +/- 8 years) the effect
      of zinc supplementation (22 mg/day as zinc gluconate) during 30 days, and
      discontinuation using placebo (maltodextrin) during the following 30 days, on
      plasma zinc and copper concentrations, serum thyroid hormones, insulin and
      glucose levels, and HOMA2-IR. Compared to baseline, plasma zinc and Zn:Cu plasma
      ratio increased, but plasma copper decreased after zinc supplementation (day 30)
      and discontinuation (day 60) (p < 0.05). Zn supplementation and discontinuation
      had no effect on TSH, T3, and T4. Fasting serum insulin and HOMA2-IR increased
      (27% and 47%, respectively) on day 60 compared to baseline (p = 0.03), suggesting
      a delayed effect of zinc supplementation. Moreover, plasma zinc was positively
      associated with serum insulin (r = 0.87, p = 0.009) and HOMA2-IR (r = 0.81, p =
      0.03) after zinc supplementation (day 30), indicating that supplemental zinc may
      impair glucose utilization in cyclists.

PMID- 20809273
TI  - Variation in cadmium tolerance and accumulation and their relationship in wheat
      recombinant inbred lines at seedling stage.
AB  - In order to identify the variation of cadmium (Cd) tolerance and accumulation in
      wheat (Triticum aestivum L.), a study was conducted in hydroponic culture with or
      without Cd using recombinant inbred lines (RILs) consisting of 103 RILs derived
      from a cross of Chuan 35050 * Shannong 483 at seedling stage. The parameters of
      shoot height, secondary roots numbers, tiller numbers, shoot dry weights, root
      dry weights, and maximum efficiency of photosystem II photochemistry under dark
      adopted conditions were measured. Cd-tolerant indexes were then calculated as
      relative the above traits under Cd stress to those under the control. Cd
      concentration in shoot or root was determined and Cd accumulation and
      translocation were calculated. Based on the Cd-tolerant indexes, membership
      function analysis was used to determine the variation of the above parameters.
      The results showed a continuous distribution among the RILs and then the RILs
      were divided into five groups according to their tolerance. Lines 76 and 17 were
      considered as the most Cd-tolerant lines while lines 103 and 51 were as the most
      Cd-sensitive lines. Meanwhile, lines 38 and 79 were with minimum Cd translocation
      ratio while lines 88 and 53 were with maximum Cd translocation ratio,
      respectively. The relationship between Cd tolerance and accumulation was not
      significant, indicating Cd tolerance and accumulation may be independent traits
      in the RILs. Thus, lines with high Cd tolerance and less Cd accumulation could be
      selected for wheat breeding.

PMID- 20809274
TI  - Chromium (VI) can activate and impair antioxidant defense system.
AB  - The changes in glutathione-dependent cycle enzymes and catalase activities under
      Cr(VI)-induced oxidative stress were investigated in two distinct cell lines: L
      41-human epithelial-like cells and HLF-fetal human diploid lung fibroblasts,
      which differ in tissue origin, proliferation, and antioxidant enzymes activities.
      The chromium concentrations from 1 to 5 MUM cause nontoxic effects and activate
      antioxidant enzymes to overcome oxidative stress. In spite of some differences in
      the endogenous antioxidant activities, both cell lines reveal the same range of
      toxic concentrations (20-30 MUM). The irreversible inhibition of glutathione
      dependent antioxidant enzymes develops under toxic concentrations and serves as a
      marker of toxicity. The endogenous antioxidant activity influences time-dependent
      expression of Cr(VI) toxicity and the dynamics of antioxidant enzymes activity
      under nontoxic conditions. The cell antioxidant defense system is an important
      marker of the cell adaptive capacity under nontoxic and toxic conditions.

PMID- 20809275
TI  - [New oral anticoagulants: better than vitamin K antagonists?].
AB  - Many years of practical use and intensive scientific research have allowed
      vitamin K antagonists to become a cornerstone of treatment of internal diseases.
      Nevertheless, limitations in pharmacokinetics and -dynamics of vitamin K
      antagonists and the availability of new drugs in regard to a targeted
      anticoagulation therapy ask for a new review of the situation. Proof of
      effectiveness for the perioperative prophylaxis of venous thrombosis after hip
      and knee replacement has already been achieved for the direct thrombin inhibitor
      dabigatran etexilate as well as for the factor Xa inhibitors rivaroxaban und
      apixaban compared to low molecular weight heparins. These new drugs are now also
      investigated in patients with internal diseases. For the long-term application (6
      or 12 months) concerning the treatment of venous thrombosis and/or stroke
      prophylaxis in patients with atrial fibrillation data is already available for
      the direct thrombin inhibitor dabigatran etexilate. Depending on its dosage its
      effectiveness in comparison with vitamin K antagonists is equal or even better
      without disadvantages in safety. However, vitamin K antagonists will remain the
      standard oral anticoagulation until open questions regarding e.g. insufficient
      therapy adherence (with termination rates up to 20%) or problems with drug
      interactions of the new competitive products have been completely answered.

PMID- 20809276
TI  - The effect of a clinical pharmacist discharge service on medication discrepancies
      in patients with heart failure.
AB  - OBJECTIVE: Heart failure patients are regularly admitted to hospital and
      frequently use multiple medication. Besides intentional changes in
      pharmacotherapy, unintentional changes may occur during hospitalisation. The aim
      of this study was to investigate the effect of a clinical pharmacist discharge
      service on medication discrepancies and prescription errors in patients with
      heart failure. SETTING: A general teaching hospital in Tilburg, the Netherlands.
      METHOD: An open randomized intervention study was performed comparing an
      intervention group, with a control group receiving regular care by doctors and
      nurses. The clinical pharmacist discharge service consisted of review of
      discharge medication, communicating prescribing errors with the cardiologist,
      giving patients information, preparation of a written overview of the discharge
      medication and communication to both the community pharmacist and the general
      practitioner about this medication. Within 6 weeks after discharge all patients
      were routinely scheduled to visit the outpatient clinic and medication
      discrepancies were measured. MAIN OUTCOME MEASURE: The primary endpoint was the
      frequency of prescription errors in the discharge medication and medication
      discrepancies after discharge combined. RESULTS: Forty-four patients were
      included in the control group and 41 in the intervention group. Sixty-eight
      percent of patients in the control group had at least one discrepancy or
      prescription error against 39% in the intervention group (RR 0.57 (95% CI 0.37
      0.88)). The percentage of medications with a discrepancy or prescription error in
      the control group was 14.6% and in the intervention group it was 6.1% (RR 0.42
      (95% CI 0.27-0.66)). CONCLUSION: This clinical pharmacist discharge service
      significantly reduces the risk of discrepancies and prescription errors in
      medication of patients with heart failure in the 1st month after discharge.

PMID- 20809277
TI  - Enhanced effects of secreted soluble factor preserve better pluripotent state of
      embryonic stem cell culture in a membrane-based compartmentalized micro
      bioreactor.
AB  - Pluripotent stem cells are under the influence of soluble factors in a diffusion
      dominant in vivo microenvironment. In order to investigate the effects of
      secreted soluble factors on embryonic stem cell (ESC) behavior in a diffusion
      dominant microenvironment, we cultured mouse ESCs (mESCs) in a membrane-based two
      chambered micro-bioreactor (MB). To avoid disturbing the cellular environment in
      the top chamber of the MB, only the culture medium of the bottom chamber was
      exchanged. Cell growth in the MB after 5 days of culture was similar to that in
      conventional 6-well plate (6-WP) and membrane-based Transwell insert (TW)
      cultures, indicating adequate nutrient supply in the MB. However, the cells
      retained higher expression of pluripotency markers (Oct4, Sox2 and Rex1) and
      secreted soluble factors (FGF4 and BMP4) in the MB. Inhibition of FGF4 activity
      in the MB and TW resulted in a similar cellular response. However, in contrast to
      the TW, inhibition of BMP4 activity revealed that autocrine action of the
      upregulated BMP4, which acted cooperatively with leukemia inhibitory factor
      (LIF), upregulated the pluripotency markers expression in the MB culture. We
      propose that BMP4 accumulated in the diffusion dominant microenvironment of the
      MB upregulated its own expression by a positive feedback mechanism-in contrast to
      the macro-scale culture systems-thereby enhancing the pluripotency of mESCs. The
      micro-scale culture platform developed in this study enables the investigation of
      the effects of soluble factors on ESCs in a diffusion dominant microenvironment,
      and is expected to be used to modulate the ESC fate choices.

PMID- 20809278
TI  - Autoimmune disease in mothers with the FMR1 premutation is associated with
      seizures in their children with fragile X syndrome.
AB  - An increased prevalence of autoimmune diseases in family members of children with
      autism spectrum disorders (ASD) has been previously reported. ASD is also a
      common problem co-occurring in children with fragile X syndrome (FXS). Why ASD
      occurs in some individuals with FXS, but not all, is largely unknown.
      Furthermore, in premutation carrier mothers, there is an increased risk for
      autoimmune diseases. This study compared the rate of ASD and other
      neurodevelopmental/behavioral problems in 61 children with FXS born to 41 carrier
      mothers who had autoimmune disease and in 97 children with FXS of 78 carrier
      mothers who did not have autoimmune disease. There were no significant
      differences in the mean age (9.61 +/- 5.59 vs. 9.41 +/- 6.31, P = 0.836),
      cognitive and adaptive functioning in children of mothers with and without
      autoimmune disease. Among children whose mothers had autoimmune disease, the odds
      ratio (OR) for ASD was 1.27 (95% CI 0.62-2.61, P = 0.5115). Interestingly, the OR
      for seizures and tics was 3.81 (95% CI 1.13-12.86, P = 0.031) and 2.94 (95% CI
      1.19-7.24, P = 0.019), respectively, in children of mothers with autoimmune
      disease compared to children of mothers without autoimmune disease. In
      conclusion, autoimmune disease in carrier mothers was not associated with the
      presence of ASD in their children. However, seizures and tics were significantly
      increased in children of mothers with autoimmune disease. This suggests a
      potential new mechanism of seizure and tic exacerbation in FXS related to an
      intergenerational influence from autoimmunity in the carrier mother.

PMID- 20809279
TI  - Comprehensive association analysis of nine candidate genes with serum 25-hydroxy
      vitamin D levels among healthy Caucasian subjects.
AB  - Vitamin D deficiency is a common public health problem in the US. It is related
      to the high risk of rickets, osteoporosis and other diseases. Currently, serum 25
      hydroxy vitamin D [25(OH)D] concentration is the best indicator of vitamin D
      status, and determination of its deficiency or sufficiency. This level has high
      heritability (28-80%). However, genes contributing to the wide variation in serum
      25(OH)D are generally unknown. In this study, we screened nine important genes in
      vitamin D metabolic pathways using 49 single nucleotide polymorphism (SNP)
      markers in a group of 156 unrelated healthy Caucasian subjects. Significant
      confounding factors that may affect serum 25(OH)D variations were used as
      covariates for the association analyses. An association test for quantitative
      trait was performed to evaluate the association between candidate genes and serum
      25(OH)D levels. Permutation was conducted for correcting multiple testing
      problems. Evidence of association was observed at SNPs in the CYP2R1 (cytochrome
      P450, family 2, subfamily R, polypeptide 1) and the GC (vitamin D binding
      protein) gene. Next, we performed a replication study for six promising SNPs in
      the gene CYP2R1 and GC, using another group of 340 unrelated healthy Caucasian
      subjects. Association analyses were conducted in the replication cohort (n = 340)
      and the pooled cohort (n = 496). The CYP2R1 gene and the GC gene remain
      significant in the pooled cohort. The results suggest that the CYP2R1 and GC
      genes may contribute to the variation of serum 25(OH)D levels in healthy
      populations.

PMID- 20809280
TI  - S-methylisothiourea induces apoptosis of herpes simplex virus-1-infected
      microglial cells.
AB  - Our study showed that S-methylisothiourea (SMT) had anti-inflammatory effects in
      treating herpes simplex encephalitis in mice, and SMT also induced apoptosis of
      herpes simplex virus (HSV-1)-infected microglial cells. Both animal and cell
      models were employed in this study. Both models included the following five
      groups: a normal control group, a virus group (HSV-1 infected), an SMT group (HSV
      1-infected + SMT (0.1 mg/10 g)), a dexamethasone group (HSV-1 infected +
      dexamethasone (2 MUg/10 g)), and an APS group (HSV-1-infected + APS (0.8 mg/10
      g)). ELISA was used to measure tumor necrosis factor (TNF)-alpha, interleukin
      (IL)-1beta, and IL-10, and Greiss method was used for measuring nitric oxide (NO)
      secretion. HE staining was performed for detecting changes in mice brain. Flow
      cytometry assay for caspase-3, caspase-8, caspase-9, and caspase-12 expressions
      was also carried out to assess apoptosis. Expressions of TNF-alpha, IL-1beta, and
      NO were significantly elevated after stimulation of microglial cells with HSV-1.
      Following SMT intervention, TNF-alpha, IL-1beta, and NO levels were significantly
      decreased. The inflammatory changes in HSV-1-infected murine brain tissues were
      also reduced. SMT induction of apoptosis of HSV-stimulated microglia seemed to be
      through three pathways: the death receptor, mitochondrially gated, and
      endoplasmic reticulum. SMT can reduce HSV-induced inflammatory insult to the
      brain. Its mechanism of action is most probably due to the induction of
      microglial cell apoptosis.

PMID- 20809281
TI  - [Living and dying in community based housing for people with dementia. An
      exploratory qualitative study].
AB  - Community based housing for people with dementia is gaining importance. In co
      operation between the people concerned, their relatives, professionals and
      volunteers, person-centred care, nursing and guidance can be realised within
      small units. Questions regarding end of life, dying, grief and the role of
      palliative care form the basis of the exploratory qualitative study presented
      here. Coping with end of life, ethical decisions and the relevance of hospice and
      palliative care in the field are highlighted. The results of the study show that
      "shared flats for people with dementia" are good places for death and dying.
      Close relationships, good communication with relatives and highly motivated
      professionals can be regarded as powerful resources. So far only few co
      operations between hospice and palliative care exist. Areas of improvement
      encompass clinical issues and coping with bereavement.

PMID- 20809282
TI  - The frailty syndrome in general practitioner care: a pilot study.
AB  - BACKGROUND: Knowledge about frailty among patients seen by general practitioners
      (GP) is currently limited. PATIENTS AND METHODS: Frailty assessment by the
      criteria of Fried and additional documentation was performed at a GP's office.
      RESULTS: Out of 119 participating patients, 14.3% were classified as frail, 52.1%
      as prefrail, and 33.6% as not frail. Frailty was associated with comorbidity, the
      number of drugs prescribed, depressive symptoms, cognitive function, and
      frequency of falls. CONCLUSION: The prevalence of frailty is high among the
      cohort of elderly persons seen by a GP. Routine frailty assessment will help to
      direct preventive and therapeutic interventions.

PMID- 20809283
TI  - 100 kV versus 120 kV: effective reduction in radiation dose?

PMID- 20809284
TI  - Lipase-catalyzed synthesis of two new antioxidants: 4-O- and 3-O-palmitoyl
      chlorogenic acids.
AB  - Chlorogenic acid (5-caffeoyl quinic acid (CQA)) extracted from Hydrangea
      macrophylla (44%, w/w) with 98% purity, was acylated with palmitic acid by
      Novozym 435 to yield mono-acylated CQA. Acylation of CQA was achieved in 2-methyl
      2-butanol at 60 degrees C, and yielded two mono-acylated products: a major
      product acylated at the C-4 of the quinic moiety (4-O-palmitoyl chlorogenic acid)
      and a minor product acylated at the C-3 (3-O-palmitoyl chlorogenic acid). The
      bioconversions obtained in 7 days ranged from 14 to 60% and were influenced by
      the molar ratio of palmitic acid/CQA, which ranged from 10 to 80. The
      regioselectivity (4-O-palmitoyl/3-O-palmitoyl ratio) of the reaction was also
      affected by the molar ratio, and ranged from 90 to 70%. The scavenging activities
      against 1,1-diphenyl-2-picryl-hydrazyl radicals demonstrated that these palmitoyl
      CQA derivatives are associated with antioxidant activity (70% vs CQA).

PMID- 20809285
TI  - Characterization of a recombinant thermostable L: -rhamnose isomerase from
      Thermotoga maritima ATCC 43589 and its application in the production of L-lyxose
      and L-mannose.
AB  - A putative L-rhamnose isomerase (RhaA) from Thermotoga maritima was purified with
      a specific activity of 55 U/mg by His-Trap affinity chromatography. The native
      enzyme was estimated as a 46 kDa tetramer by gel filtration chromatography. The
      half-lives of the enzyme at 75, 80, 85, 90 and 95 degrees C were 773, 347, 187,
      118, and 65 h, respectively, indicating that it is the most thermostable of all
      RhaAs. Under the optimum conditions of pH 8.0, 85 degrees C, and 1 mM Mn(2+),
      RhaA with 100 U enzyme/ml converted 500 L-xylulose/l to 225 g/l L-lyxose after 3
      h, and converted 500 L-fructose/l to 175 g/l L-mannose after 5 h.

PMID- 20809286
TI  - Towards an integrated system for bio-energy: hydrogen production by Escherichia
      coli and use of palladium-coated waste cells for electricity generation in a fuel
      cell.
AB  - Escherichia coli strains MC4100 (parent) and a mutant strain derived from this
      (IC007) were evaluated for their ability to produce H(2) and organic acids (OAs)
      via fermentation. Following growth, each strain was coated with Pd(0) via
      bioreduction of Pd(II). Dried, sintered Pd-biomaterials ('Bio-Pd') were tested as
      anodes in a proton exchange membrane (PEM) fuel cell for their ability to
      generate electricity from H(2). Both strains produced hydrogen and OAs but
      'palladised' cells of strain IC007 (Bio-Pd(IC007)) produced ~threefold more power
      as compared to Bio-Pd(MC4100) (56 and 18 mW respectively). The power output used,
      for comparison, commercial Pd(0) powder and Bio-Pd made from Desulfovibrio
      desulfuricans, was ~100 mW. The implications of these findings for an integrated
      energy generating process are discussed.

PMID- 20809287
TI  - Can diffusion tensor metrics help in preoperative grading of diffusely
      infiltrating astrocytomas? A retrospective study of 36 cases.
AB  - INTRODUCTION: Diffusion weighted imaging and diffusion tensor imaging (DTI) give
      information about the amount and directionality of water diffusion occurring in a
      given tissue. Here we study the role of diffusion tensor metrics including
      fractional anisotropy (FA) and spherical anisotropy (CS) in preoperative grading
      of diffusely infiltrating astrocytomas. METHODS: We performed DTI in 38 patients
      with pathologically proven diffusely infiltrating astrocytomas, who were
      classified into two groups, i.e., 15 patients with high-grade astrocytoma (HGAs,
      WHO grade III and IV) and 23 patients with low-grade astrocytoma (LGAs, WHO grade
      II). We measured maximum FA and minimum CS values in all cases from tumor.
      Histopathological diagnosis was established in all cases. RESULTS: The mean
      maximum FA values were higher in HGA (0.583 +/- 0.104) than LGA (0.295 +/-
      0.058), while mean minimum CS values were lower in HGA (0.42 +/- 0.121) than LGA
      (0.722 +/- 0.061). The difference in the diffusion tensor indices between HGA and
      LGA was found to be statistically significant with P value of <0.001. Keeping
      cutoff FA value of 0.4, all HGAs showed higher maximum FA values, and all LGAs
      showed lower maximum FA values. Also, all HGAs showed minimum CS values less than
      a cutoff value of 0.6, and all LGAs showed minimum CS values higher than 0.6.
      CONCLUSION: Diffusion tensor metrics such as maximum FA and minimum CS can help
      to differentiate HGA from LGA.

PMID- 20809289
TI  - Primary production in a subtropical stratified coastal lagoon--contribution of
      anoxygenic phototrophic bacteria.
AB  - Anaerobic anoxygenic phototrophic bacteria can be found in the suboxic waters of
      shallow stratified coastal systems, and may play important roles in the total
      primary production of subtropical stratified coastal lagoons. We investigated the
      spatiotemporal variability of light CO(2) fixation and net oxygen production in
      the stratified Conceicao Lagoon (Brazil) in summer and fall of 2007, as well as
      the contribution of bacteriochlorophyll a (BChl a)-containing bacteria to
      photosynthetically driven electron transfer. Both chlorophyll a (Chl a) and BChl
      a varied in space, while only BChl a varied in time (three-fold increase from
      summer to fall). In summer, net oxygen production and light CO(2) fixation were
      correlated, with both having higher rates with higher Chl a concentrations in the
      enclosed region of the lagoon. In fall, CO(2) fixation was decoupled from oxygen
      production. Denaturing gradient gel electrophoresis revealed that bacterial
      communities of oxic site 12 and suboxic site 33 formed one cluster, different
      from other oxic samples within the lagoon. In addition, BChl a/Chl a ratios at
      these sites were high, 40% and 45%, respectively. Light acted as the main factor
      controlling the BChl a concentration and CO(2) fixation rates. High turbidity
      within the enclosed area of the lagoon explained high BChl a and decoupling
      between CO(2) fixation and oxygen production in oxygenated waters. Contribution
      of purple sulfur bacteria to total bacterial density in suboxic waters was 1.2%,
      and their biomass contributed to a much higher percentage (12.2%) due to their
      large biovolume. Our results indicate a significant contribution of anaerobic
      anoxygenic bacteria to the primary production of the "dead zone" of Conceicao
      Lagoon.

PMID- 20809288
TI  - Annual and seasonal variation in the phyllosphere bacterial community associated
      with leaves of the southern Magnolia (Magnolia grandiflora).
AB  - The phyllosphere contains a diverse bacterial community that can be intimately
      associated with the host plant; however, few studies have examined how the
      phyllosphere community changes over time. We sampled replicate leaves from a
      single magnolia (Magnolia grandiflora) tree in the winter of three consecutive
      years (2007-2009) as well as during four seasons of 1 year (2008) and used
      molecular techniques to examine seasonal and year-to-year variation in bacterial
      community structure. Multivariate analysis of denaturing gradient gel
      electrophoresis profiles of 16S rRNA gene fragments revealed minimal leaf to leaf
      variation and much greater temporal changes, with the summer (August 2008) leaf
      community being most distinct from the other seasons. This was confirmed by
      sequencing and analysis of 16S rRNA gene clone libraries generated for each
      sample date. All phyllosphere communities were dominated by Alphaproteobacteria,
      with a reduction in the representation of certain Beijerinckiaceae during the
      summer and a concurrent increase in the Methylobacteriaceae being the most
      significant seasonal change. Other important components of the magnolia
      phyllosphere included members of the Bacteroidetes, Acidobacteria, and
      Actinobacteria, with the latter two lineages also showing differences in their
      representation in samples collected at different times. While the leaf-associated
      bacterial community sampled at the same time of year in three separate years
      showed some similarities, generally these communities were distinct, suggesting
      that while there are seasonal patterns, these may not be predictable from year to
      year. These results suggest that seasonal differences do occur in phyllosphere
      communities and that broad-leafed evergreen trees such as M. grandiflora may
      present interesting systems to study these changes in the context of changing
      environmental conditions.

PMID- 20809290
TI  - Characterization and global gene expression of F- phenocopies during Escherichia
      coli biofilm formation.
AB  - The ecological role of horizontal gene transfer within biofilms has been recently
      investigated, and it has been reported that conjugation directly induces bacteria
      to form biofilms via expression of conjugative pili. In this report, we described
      the contribution of bacterial conjugation during biofilm formation by Escherichia
      coli harboring a natural IncF conjugative F plasmid (F(+)). We showed that cell
      to-cell pili interactions through the homosexual mating-pair formation among F(+)
      * F(+) cells (namely, F(-) phenocopy phenomenon) promote E. coli biofilm
      formation at the early development stage. The presence of F(+) * F(+) population
      is the result from heterogeneity within biofilms leading to sessile bacteria that
      grow at different rates, in which the late-stationary phase cells acted as F(-)
      phenocopy cells. According to global transcriptional analysis, the biofilm
      lifestyle shared similar gene expression pattern with F(-) phenocopies. F(-)
      phenocopy cells expressed specific sets of chromosomal genes (e.g., genes for
      general stress response and two-component systems) that control the regulation
      regions of F transfer operon by blocking surface exclusion proteins and DNA
      transfer machineries. However, mating-pair proteins were stabilized and
      consequently promoted F(+) * F(+) pili assembly. Thus, F(-) phenocopy phenomenon
      is an effective adaptive behavior of bacterial cells during biofilm formation.

PMID- 20809291
TI  - NPC-16, a novel naphthalimide-polyamine conjugate, induced apoptosis and
      autophagy in human hepatoma HepG2 cells and Bel-7402 cells.
AB  - The antitumor effects and molecular mechanism of NPC-16, a novel naphthalimide
      polyamine conjugate, were evaluated in HepG2 cells and Bel-7402 cells. Apoptosis
      and necrosis were evaluated by Annexin V-FITC detection kit, and autophagy by
      acridine orange and Lyso-Tracker Red staining. The change of mitochondrial
      transmembrane potential was measured using rhodamine 123 staining. The protein
      expression of Beclin 1, LC3 II and mTOR, p70S6 K, 14-3-3, caspase, and Bcl-2
      family members was detected by immunofluorescence assays and Western Blot. Here,
      we elucidated the nature of cellular response of HepG2 cells and Bel-7402 cells
      to NPC-16 at IC(50). NPC-16 induced caspase-dependent apoptosis via the
      mitochondrial pathway and death receptor pathway in Bel-7402 cells. Differently,
      NPC-16 triggered HepG2 cells both apoptosis and autophagy, further autophagy
      facilitated cellular apoptosis. Furthermore, mTOR signal pathway was involved in
      NPC-16-mediated autophagy in HepG2 cells. Thus, NPC-16 may be useful as a
      potential template for investigation the molecular mechanism of naphthalimide
      polyamine conjugate against hepatocellular carcinoma.

PMID- 20809292
TI  - A mathematical criterion based on phase response curves for stability in a ring
      of coupled oscillators.
AB  - Canavier et al. (1997) used phase response curves (PRCs) of individual
      oscillators to characterize the possible modes of phase-locked entrainment of an
      N-oscillator ring network. We extend this work by developing a mathematical
      criterion to determine the local stability of such a mode based on the PRCs. Our
      method does not assume symmetry; neither the oscillators nor their connections
      need be identical. To use these techniques for predicting modes and determining
      their stability, one need only determine the PRC of each oscillator in the ring
      either experimentally or from a computational model. We show that network
      stability cannot be determined by simply testing the ability of each oscillator
      to entrain the next. Stability depends on the number of neurons in the ring, the
      type of mode, and the slope of each PRC at the point of entrainment of the
      respective neuron. We also describe simple criteria which are either necessary or
      sufficient for stability and examine the implications of these results.

PMID- 20809294
TI  - [Continuity and change].

PMID- 20809295
TI  - [Second line AUO study AB35/09 of metastasized urothelial cell carcinoma].

PMID- 20809296
TI  - [Ferdinand Eisenberger Scholarships].

PMID- 20809300
TI  - Fluorescence in situ hybridization (FISH), basic principles and methodology.
AB  - Fluorescence in situ hybridization (FISH) is widely used for the localization of
      genes and specific genomic regions on target chromosomes, both in metaphase and
      interphase cells. The applications of FISH are not limited to gene mapping or the
      study of genetic rearrangements in human diseases. Indeed, FISH is increasingly
      used to explore the genome organization in various organisms and extends to the
      study of animal and plant biology. We have described the principles and basic
      methodology of FISH to be applied to the study of metaphase and interphase
      chromosomes.

PMID- 20809301
TI  - Fluorescence in situ hybridization on DNA halo preparations and extended
      chromatin fibres.
AB  - Although many fluorescence in situ hybridisation (FISH) protocols involve the use
      of intact, fixed nuclei, the resolution achieved is not always sufficient,
      especially for physical mapping. In light of this, several techniques are
      commonly used to create extended chromatin fibres or extruded loops of DNA. As a
      result, it is possible to visualise and distinguish regions of the genome at a
      resolution higher than that attained with conventional preparations for FISH.
      Such methodologies include fibre-FISH and the DNA halo preparation. While fibre
      FISH involves the stretching of chromatin fibres across a glass slide, the DNA
      halo preparation is somewhat more complex; whereby DNA loops instead of chromatin
      fibres are generated from interphase nuclei. Furthermore, the DNA halo
      preparation coupled with FISH is a useful tool for examining interactions between
      the inextractable nuclear matrix and the cell's genome.In this chapter, we
      describe how to successfully generate extended chromatin fibres and extruded DNA
      loops. We will also provide detailed methodologies for coupling either procedure
      with two distinct FISH procedures; 2D-FISH, which allows for the visualisation of
      specific chromosomal regions, while telomere peptide nucleic acid (PNA) FISH,
      enables the detection of all telomeres present within human nuclei.

PMID- 20809302
TI  - Detection of nascent RNA transcripts by fluorescence in situ hybridization.
AB  - The development of cellular diversity within any organism depends on the timely
      and correct expression of differing subsets of genes within each tissue type.
      Many techniques exist which allow a global, average analysis of RNA expression;
      however, RNA-FISH permits the sensitive detection of specific transcripts within
      individual cells while preserving the cellular morphology. The technique can
      provide insight into the spatial and temporal organization of gene transcription
      as well the relationship of gene expression and mature RNA distribution to
      nuclear and cellular compartments. It can also reveal the intercellular variation
      of gene expression within a given tissue. Here, we describe RNA-FISH
      methodologies that allow the detection of nascent transcripts within the cell
      nucleus as well as protocols that allow the detection of RNA alongside DNA or
      proteins. Such techniques allow the placing of gene transcription within a
      functional context of the whole cell.

PMID- 20809303
TI  - Fluorescence in situ hybridization analysis of formalin fixed paraffin embedded
      tissues, including tissue microarrays.
AB  - Formalin fixed paraffin embedded (FFPE) material is frequently the most
      convenient readily available source of diseased tissue, including tumors.
      Multiple cores of FFPE material are being used increasingly to construct tissue
      microarrays (TMAs) that enable simultaneous analyses of many archival samples.
      Fluorescence in situ hybridization (FISH) is an important approach to analyze
      FFPE material for specific genetic aberrations that may be associated with tumor
      types or subtypes, cellular morphology, and disease prognosis. Annealing, or
      hybridization of labeled nucleic acid sequences, or probes, to detect and locate
      one or more complementary nucleic acid sequences within fixed tissue sections
      allows the detection of structural (translocation/inversion) and numerical
      (deletion/gain) aberrations and their localization within tissues. The robust
      protocols described include probe preparation, hybridization, and detection and
      take 2-3 days to complete. A protocol is also described for the stripping of
      probes for repeat FISH in order to maximize the use of scarce tissue resources.

PMID- 20809304
TI  - Fluorescence in situ hybridization (FISH) on tissue cryosections.
AB  - Recent progress in the understanding of the spatial organization of nuclear
      functions owes a lot to fluorescence in situ hybridization (FISH) methodology.
      The majority of studies using this technology have been carried out using
      cultured cells. However, nuclear processes in whole organisms, may be to a
      notable degree, different from those in cultured cells and actually not similar
      across different tissues. Therefore, for better understanding of nuclear
      processes in ex vivo organismal material, it is necessary to study nuclear
      organization in sections of tissue. FISH on sections is still not common in
      nuclear biology studies mostly due to methodological problems. The protocol
      suggested in this chapter is based on several years experience in hybridizing
      different probes on cryosections of various tissues.

PMID- 20809305
TI  - Multiplex fluorescence in situ hybridization (M-FISH).
AB  - Multiplex in situ hybridization (M-FISH) is a 24-color karyotyping technique and
      is the method of choice for studying complex interchromosomal rearrangements. The
      process involves three major steps. Firstly, the multiplex labeling of all
      chromosomes in the genome with finite numbers of spectrally distinct fluorophores
      in a combinatorial fashion, such that each homologous pair of chromosomes is
      uniquely labeled. Secondly, the microscopic visualization and digital acquisition
      of each fluorophore using specific single band-pass filter sets and dedicated M
      FISH software. These acquired images are then superimposed enabling individual
      chromosomes to be classified based on the fluor composition in accordance with
      the combinatorial labeling scheme of the M-FISH probe cocktail used. The third
      step involves the detailed analysis of these digitally acquired and processed
      images to resolve structural and numerical abnormalities.

PMID- 20809307
TI  - 3D-FISH on cultured cells combined with immunostaining.
AB  - Fluorescence in situ hybridization on three-dimensionally preserved nuclei (3D
      FISH), in combination with immunocytochemistry and 3D fluorescence microscopy, is
      a key tool to analyze the functional organization of the interphase nucleus. In
      the last decade, 3D-FISH on cultured cells has become a routine technique and is
      now widely used in nuclear biology. This method allows visualization of
      chromosome territories, chromosome subregions, single genes, and RNA transcripts
      preserving their spatial positions in the cell nucleus. In many cases, it is
      desirable to combine 3D-FISH and immunostaining to map DNA/RNA and protein
      targets in the same cells. Some steps of the FISH procedure, however, may
      interfere with immunostaining and special efforts have to be done to combine FISH
      and antibody staining successfully. The protocol suggested in this chapter
      describes three variants of combined 3D-FISH and immunostaining which have been
      successfully used in our laboratory for many years.

PMID- 20809306
TI  - Optical mapping of protein-DNA complexes on chromatin fibers.
AB  - Immunofluorescence (IF) and Fluorescence in situ Hybridization (FISH) are
      conventional methods used to study the structure and organization of metaphase
      chromosomes and interphase nuclei. Using these techniques, the locations of whole
      chromosome territories, chromatin subdomains, and specific DNA sequences can be
      evaluated at kilobase or megabase resolution. Even higher resolution of the
      spatial relationships of proteins and DNA can be achieved using combined IF-FISH
      on extended chromatin fibers. This method of optical mapping is a powerful system
      for localizing molecular probes along released chromatin fibers and visualizing
      small (<20 kb) or large (20-5,000 kb) chromosomal domains. Chromatin fiber
      analysis can fill the gaps in resolution between classical chromosome studies and
      molecular analyses, such as chromatin immunoprecipitation (ChIP) that evaluates
      chromatin organization at the level of single or multiple nucleosomes. In this
      chapter, the conceptual and technical aspects of chromatin fiber IF-FISH are
      presented, along with examples of successful applications.

PMID- 20809308
TI  - The Comet-FISH assay for the analysis of DNA damage and repair.
AB  - In this chapter, I describe the alkaline single-cell gel electrophoresis (Comet
      assay) combined with fluorescence in situ hybridization (FISH) technology, used
      in our laboratory, to study the incidence and repair of lesions induced in human
      cells by ultraviolet light. The Comet-FISH method permits the simultaneous and
      comparative analysis of DNA damage and its repair throughout the genome and in
      defined chromosomal regions. This very sensitive approach can be applied to any
      lesion, such as those induced by chemical carcinogens and products of cellular
      metabolism that can be converted to DNA single- or double-strand breaks. The
      unique advantages and limitations of the method for particular applications are
      discussed.

PMID- 20809309
TI  - Direct in situ hybridization with oligonucleotide functionalized quantum dot
      probes.
AB  - Coming from the material sciences, fluorescent semiconductor nanocrystals, also
      known as quantum dots (QDs), have emerged as powerful fluorescent probes for a
      wide range of biological imaging applications. QDs have several advantages over
      organic dyes which include higher brightness, better resistance to
      photobleaching, and simplified multicolor target detection. In this chapter, we
      describe a rapid assay for the direct imaging of multiple repetitive subnuclear
      genetic sequences using QD-based FISH probes. Streptavidin-coated QDs (SAvQDs)
      are functionalized with short biotinylated oligonucleotides and used in a single
      hybridization/detection step. These QD-FISH probes penetrate both intact
      interphase nuclei and metaphase chromosomes and show good targeting of dense
      chromatin domains. Importantly, the broad absorption spectra of QDs allows two
      sequence specific QD-FISH probes of different colors to be simultaneously imaged
      with a single laser excitation wavelength. This method, which requires minimal
      custom conjugation, is easily expandable and offers the experimentalist a new
      alternative to increase flexibility in multicolor cytogenetic FISH applications
      of repetitive DNAs.

PMID- 20809310
TI  - LNA-FISH for detection of microRNAs in frozen sections.
AB  - MicroRNAs (miRNAs) are small ( approximately 22 nt) noncoding RNA molecules that
      regulate the expression of protein coding genes either by cleavage or
      translational repression. miRNAs comprise one of the most abundant classes of
      gene regulatory molecules in multicellular organisms. Yet, the function of miRNAs
      at the tissue, cell, and subcellular levels is still to be explored. Especially,
      determining spatial and temporal expression of miRNAs has been a challenge due to
      their short size and low expression. This protocol describes a fast and effective
      method for detection of miRNAs in frozen tissue sections using fluorescence in
      situ hybridization. The method employs the unique recognition power of locked
      nucleic acids as probes together with enhanced detection power of the tyramide
      signal amplification system for detection of miRNAs in frozen tissues of human
      and animal origin within a single day.

PMID- 20809311
TI  - Chromosome Orientation fluorescence in situ hybridization or strand-specific
      FISH.
AB  - Chromosome Orientation FISH (CO-FISH) is a technique that can be used to extend
      the information obtainable from standard FISH to include the relative orientation
      of two or more DNA sequences within a chromosome. CO-FISH can determine the
      absolute 5'-to-3' direction of a DNA sequence relative to the short arm-to-long
      arm axis of the chromosome, and so was originally termed "COD-FISH" (Chromosome
      Orientation and Direction FISH). CO-FISH has been employed to detect chromosomal
      inversions associated with isochromosome formation, various pericentric
      inversions, and to confirm the origin of lateral asymmetry. More recent and
      sophisticated applications of CO-FISH include distinction between telomeres
      produced via leading- vs. lagging-strand DNA synthesis, identification of
      interstitial blocks of telomere sequence that result from inappropriate fusion to
      double-strand breaks (telomere-DSB fusion), discovery of elevated rates of
      mitotic recombination at chromosomal termini and sister chromatid exchange within
      telomeric DNA (T-SCE), establishing replication timing of mammalian telomeres
      throughout S-phase (ReD-FISH) and to identify chromosomes, in combination with
      spectral karyotyping (SKY-CO-FISH).

PMID- 20809312
TI  - COMBinatorial Oligo FISH: directed labeling of specific genome domains in
      differentially fixed cell material and live cells.
AB  - With the improvement and completeness of genome databases, it has become possible
      to develop a novel fluorescence in situ hybridization (FISH) technique called
      COMBinatorial Oligo FISH (COMBO-FISH). In contrast to other (standard) FISH
      applications, COMBO-FISH makes use of a bioinformatic approach for probe set
      design. By means of computer genome database search, oligonucleotide stretches of
      typical lengths of 15-30 nucleotides are selected in such a way that they all
      colocalize within a given genome (gene) target. Typically, probe sets of about 20
      40 stretches are designed within 50-250 kb, which is enough to get an increased
      fluorescence signal specifically highlighting the target from the background.
      Although "specific colocalization" is the only necessary condition for probe
      selection, i.e. the probes of different lengths can be composed of purines and
      pyrimidines, we additionally refined the design strategy restricting the probe
      sets to homopurine or homopyrimidine oligonucleotides so that depending on the
      probe orientation either double (requiring denaturation of the target double
      strand) or triple (omitting denaturation of the target strand) strand bonding of
      the probes is possible. The probes used for the protocols described below are DNA
      or PNA oligonucleotides, which can be synthesized by established automatized
      techniques. We describe different protocols that were successfully applied to
      label gene targets via double- or triple-strand bonding in fixed lymphocyte cell
      cultures, bone marrow smears, and formalin-fixed, paraffin-wax embedded tissue
      sections. In addition, we present a procedure of probe microinjection in living
      cells resulting in specific labeling when microscopically detected after
      fixation.

PMID- 20809313
TI  - Simultaneous visualization of FISH signals and bromo-deoxyuridine incorporation
      by formamide-free DNA denaturation.
AB  - The replication timing of different DNA sequences in the mammalian cell nucleus
      is a tightly regulated system, which affects important cellular processes such as
      genes expression, chromatin epigenetic marking, and maintenance of chromosome
      structure. For this reason, it is important to study the replication properties
      of specific sequences, to determine for example, if the replication timing varies
      in different tissues, or in the presence of specific reagents, such as hormones,
      or other biologically active molecules. In this chapter, we present a technique,
      which allows identification of specific DNA sequences by fluorescence in situ
      hybridization (FISH) and simultaneously analyses the incorporation of a thymidine
      analogue, 5-bromo-2-deoxyuridine (BrdU), to mark DNA replication. First, tissue
      culture cells are synchronized at the beginning of the S-phase. BrdU is then
      added, either at specific time-points during S-phase or during the whole of the
      cell cycle. After harvesting the cells, the chromosomal DNA is hybridized to FISH
      probes that identify specific DNA sequences; this is performed without the
      teratogen formamide normally used in FISH. Finally, the cell preparations are
      analysed with an epifluorescence microscope to determine if the sequence of
      interest incorporates BrdU and in which point of the S-phase.

PMID- 20809314
TI  - CryoFISH: fluorescence in situ hybridization on ultrathin cryosections.
AB  - The visualization of cellular structures and components has become an invaluable
      tool in biological and medical sciences. Imaging subcellular compartments and
      single molecules within a cell has prompted the development of a wide range of
      sample preparation techniques as well as various microscope devices to obtain
      images with increased spatial resolution. Here, we present cryoFISH, a method for
      fluorescence in situ hybridization (FISH) on thin ( approximately 150 nm thick)
      cryosections from sucrose-embedded fixed cells or tissues. CryoFISH can be used
      in combination with immunodetection (IF) of other cellular components. The main
      advantages of cryoFISH and cryoIF over whole-cell labeling methods are increased
      spatial resolution with confocal microscopy, greater sensitivity of detection due
      to increased probe accessibility, and better image contrast. CryoFISH and cryoIF
      methods typically used on samples fixed in conditions that preserve
      ultrastructure, are compatible with the labeling of cells in their tissue context
      and are ideal for correlative studies that compare fluorescence with electron
      microscopy.

PMID- 20809315
TI  - Characterization of chromosomal rearrangements using multicolor-banding (MCB/m
      band).
AB  - Molecular cytogenetics and especially fluorescence in situ hybridization (FISH)
      banding approaches are nowadays standard for the exact characterization of
      simple, complex, and cryptic chromosomal aberrations within the human genome.
      FISH-banding techniques are any kind of FISH techniques, which provide the
      possibility to characterize simultaneously several chromosomal subregions smaller
      than a chromosome arm. FISH banding methods fitting that definition may have
      quite different characteristics, but share the ability to produce a DNA-specific
      chromosomal banding. While the standard techniques such as G-bands by Trypsin
      using Giemsa banding lead to a protein-related black and white banding pattern,
      FISH-banding techniques are DNA-specific, more colorful, and thus, more
      informative. At present, the most frequently applied FISH banding technique is
      the multicolor banding (MCB/m-band) approach. MCB/m-band is based on region
      specific microdissection libraries, producing changing fluorescence intensity
      ratios along the chromosomes. Here we describe the FISH-banding technique MCB/m
      band and illustrate how to apply it for characterization of chromosomal
      breakpoints with a minimal number of FISH experiments.

PMID- 20809316
TI  - Visualizing nucleic acids in living cells by fluorescence in vivo hybridization.
AB  - The analysis of the spatial-dynamic properties of DNA and RNA molecules in living
      cells will greatly extend our knowledge of genome organization and gene
      expression regulation in the cell nucleus. The development of hybridization
      methods allowing detection of specific endogenous DNA and RNA sequences in living
      cells has therefore been a challenge for many years. However, there are many
      technical issues that have proven so far to be difficult, or even impossible, to
      overcome. As a result, in most situations, the application of in vivo
      hybridization methods is currently limited to the visualization of highly
      repetitive DNA sequences or abundant RNA species. We describe a protocol that
      enables the visualization and tracking of telomeres in living cells by
      hybridization with a fluorescent peptide nucleic acid (PNA) probe. Furthermore,
      we describe a method that allows the detection of abundant endogenous RNAs in
      living cells by microinjecting fluorescently labeled complementary 2'-O-methyl
      RNA probes.

PMID- 20809317
TI  - Quality control in FISH as part of a laboratory's quality management system.
AB  - Quality control in the laboratory setting requires the establishment of a quality
      management system (QMS) that covers training, standard operating procedures,
      internal quality control, validation of tests, and external quality assessment
      (EQA). Laboratory accreditation through inspection by an external body is also
      desirable as this provides an effective procedure for assuring quality and also
      reassures the patient that the laboratory is working to acceptable international
      standards. The implementation of fluorescence in situ hybridisation (FISH) in the
      routine diagnostic laboratory requires rigorous quality control with attention to
      when it is appropriate to apply the technology, a systematic approach to the
      validation of probes, policies and procedures documenting the analytical validity
      of all FISH tests performed, technical procedures involved, and a comprehensive
      means of reporting results. Knowledge of the limitations of any FISH test is
      required in relation to the probe and/or tissue being examined, since errors of
      analysis and interpretation can result in incorrect patient management. A
      structured QMS with internal quality control and regular audits will minimise the
      error rate.

PMID- 20809318
TI  - FlashFISH: "same day" prenatal diagnosis of common chromosomal aneuploidies.
AB  - Fluorescence in situ hybridization (FISH) and quantitative fluorescence (QF)-PCR
      are rapid molecular methods that test for common chromosomal aneuploidies in
      prenatal diagnosis. While cytogenetic analysis requires approximately 7-14 days
      before fetal karyotypes are available, these molecular methods release results of
      sex chromosome aneuploidies, Down syndrome, Edward's syndrome, and Patau's
      syndrome within 24-48 h of fetal sampling, alleviating parental anxiety. However,
      specific diagnosis or exclusion of aneuploidy should be available within the same
      day of amniocentesis. We developed "FlashFISH," a low cost FISH method that
      allows accurate results to be reported within 2 h of fetal sampling. Here, we
      report our experience of using FlashFISH in prenatal diagnosis, and we illustrate
      in detail the protocols used for the purpose in our laboratory.

PMID- 20809319
TI  - FISH for pre-implantation genetic diagnosis.
AB  - Pre-implantation genetic diagnosis (PGD) is an established alternative to pre
      natal diagnosis, and involves selecting pre-implantation embryos from a cohort
      generated by assisted reproduction technology (ART). This selection may be
      required because of familial monogenic disease (e.g. cystic fibrosis), or because
      one partner carries a chromosome rearrangement (e.g. a two-way reciprocal
      translocation). PGD is available for couples who have had previous affected
      children, and/or in the case of chromosome rearrangements, recurrent
      miscarriages, or infertility. Oocytes aspirated following ovarian stimulation are
      fertilized by in vitro immersion in semen (IVF) or by intracytoplasmic injection
      of individual spermatocytes (ICSI). Pre-implantation cleavage-stage embryos are
      biopsied, usually by the removal of a single cell on day 3 post-fertilization,
      and the biopsied cell is tested to establish the genetic status of the
      embryo.Fluorescence in situ hybridization (FISH) on the fixed nuclei of biopsied
      cells with target-specific DNA probes is the technique of choice to detect
      chromosome imbalance associated with chromosome rearrangements, and to select
      female embryos in families with X-linked disease for which there is no mutation
      specific test. FISH has also been used to screen embryos for sporadic chromosome
      aneuploidy (also known as PGS or PGD-AS) in order to try and improve the
      efficiency of assisted reproduction; however, due to the unacceptably low
      predictive accuracy of this test using FISH, it is not recommended for routine
      clinical use.This chapter describes the selection of suitable probes for single
      cell FISH, assessment of the analytical performance of the test, spreading
      techniques for blastomere nuclei, and in situ hybridization and signal scoring,
      applied to PGD in a clinical setting.

PMID- 20809320
TI  - PNA-FISH on human sperm.
AB  - Peptide nucleic acids (PNAs) constitute a remarkable new class of synthetic
      nucleic acids analogs, based on peptide-like backbone. This structure gives PNAs
      the capacity to hybridize with high affinity and specificity to complementary RNA
      and DNA sequences. Over the last few years, the use of PNAs has proven its
      efficacy in cytogenetics for the rapid in situ identification of human
      chromosomes. Multicolour PNA-FISH protocols have been described and their
      adaptation to human spermatozoa has allowed the development of a new and fast
      procedure, which can advantageously be used for the assessment of aneuploidy in
      male gametes.

PMID- 20809321
TI  - POD-FISH: a new technique for parental origin determination based on copy number
      variation polymorphism.
AB  - With the progress of array technologies and the enabled screening of individual
      human genomes, a new kind of polymorphism has been described - the so-called copy
      number variation (CNV) polymorphism. Copy number variants can be found in around
      12% of the human genome sequence and have a size of up to several hundred
      kilobase pairs. These variants can not only differ between individuals, but also
      between corresponding alleles on homologous chromosomes. We recently developed a
      cytological assay for parental origin determination that relies on the design of
      CNV-based sets of probes for fluorescence in situ hybridization (POD-FISH). Here
      we describe an improved POD-FISH protocol that exploits "high frequency" variants
      for better discrimination of homologous chromosomes.

PMID- 20809322
TI  - Sequence-based high resolution chromosomal comparative genomic hybridization
      (CGH).
AB  - We aimed to devise an appropriate method to directly link the fluorescence
      profile of chromosomal copy number alterations detected by chromosomal
      comparative genomic hybridization (cCGH) or any other hybridization or staining
      information with the genome sequence data. Our goal was to establish an internal
      anchoring system that could facilitate profile alignment and thus increase the
      resolution of cCGH. We were able to achieve the alignment of chromosomes with
      gene mapping data by superimposition of (a) the fluorescence intensity pattern of
      a sequence-specific fluorochrome (GGCC binding specificity), (b) the cCGH
      fluorescence intensity profile of individual chromosomes, and (c) the GGCC motif
      density profile extracted from a genome sequence database. The adjustment of
      these three pieces of information allowed us to precisely localize, in cytobands
      and mega base pairs (Mb), regions of genomic alterations such as gene
      amplifications, gains, or losses. The combined visualization of sequence
      information and cCGH data together with application of the Warp tool, presented
      here, considerably improves the cCGH accuracy by increasing its resolution from
      10 to 20 Mb to less than 2 Mb.

PMID- 20809323
TI  - ImmunoFISH on isolated nuclei from paraffin-embedded biopsy material.
AB  - The detection of genetic abnormalities in paraffin sections by fluorescence in
      situ hybridization (FISH) is widely used in clinical practice to detect
      amplification of the ERB2 gene in breast carcinoma and various chromosomal
      translocations in lymphomas and soft tissue tumors. However, interpretation of
      FISH signals in tissue sections may be difficult due to overlapping nuclei and
      nuclear truncation artifacts. Some of these shortcomings may be avoided by the
      use of isolated nuclear preparations. However, identification of cell populations
      may be difficult in detached cells removed from their histological context. We
      have described an optimized immunoFISH technique on isolated nuclear suspension,
      which combines the benefits of studying isolated cells derived from paraffin
      embedded tissues by FISH analysis with the ability to detect cell lineage and
      other markers by immunofluorescence.

PMID- 20809324
TI  - Fluorescence in situ hybridization on 3D cultures of tumor cells.
AB  - Genomes are spatially highly organized within interphase nuclei. Spatial genome
      organization is increasingly linked to genome function. Fluorescence in situ
      hybridization (FISH) allows the visualization of specific regions of the genome
      for spatial mapping. While most gene localization studies have been performed on
      cultured cells, genome organization is likely to be different in the context of
      tissues. Three-dimensional (3D) culture model systems provide a powerful tool to
      study the contribution of tissue organization to gene expression and
      organization. However, FISH on 3D cultures is technically more challenging than
      on monocultures. Here, we describe an optimized protocol for interphase DNA FISH
      on 3D cultures of the breast epithelial cell line MCF-10A.B2, which forms breast
      acini and can be used as a model for early breast cancer.

PMID- 20809325
TI  - Simultaneous ultrasensitive subpopulation staining/hybridization in situ (SUSHI)
      in HIV-1 disease monitoring.
AB  - The field of virology is undergoing a revolution as diagnostic tests and new
      therapies are allowing clinicians to treat, monitor, and predict outcomes of
      viral diseases. The majority of these techniques, however, destroy the factory of
      viral production and the information inherent in the reservoir - the cell. In
      this chapter, we describe a technique that combines cell surface
      immunophenotyping (to unequivocally identify cell types) and ultrasensitive
      fluorescence in situ hybridization (U-FISH) for HIV-1 to detect productively
      infected cells. Identification of virus and host (cells) allows earlier detection
      of changes in viral production and viral suppression but most importantly allows
      clinicians to monitor response to anti-viral therapy on a cell-by-cell and tissue
      by-tissue basis taking into account the fact that the human body consists of very
      different, distinct compartments with unique selection pressures exerted on the
      viral life cycle.

PMID- 20809326
TI  - Detection of prokaryotic cells with fluorescence in situ hybridization.
AB  - Fluorescence in situ hybridization with rRNA targeted oligonucleotide probes is
      nowadays one of the core techniques in microbial ecology, allowing the
      identification and quantification of microbial cells in environmental samples in
      situ. Next to the classic FISH protocol, which uses fluorescently monolabelled
      probes, the more sensitive CARD-FISH (also known as TSA-FISH), which involves an
      enzyme catalyzed signal amplification step, is becoming increasingly popular.
      This chapter describes protocols for both methods. While classic FISH has the
      advantage of being relatively cheap and easy to do on morphologically diverse
      samples, CARD-FISH offers a significantly higher sensitivity, allowing the
      detection of slow growing or metabolically inactive cells, which are below the
      detection limit of classic FISH. The drawback here is the considerably higher
      price for the probes and advanced cell fixation and permeabilization requirements
      that have to be optimized for different target cells.

PMID- 20809327
TI  - FISH as a tool to investigate chromosome behavior in budding yeast.
AB  - Fluorescence in situ hybridization (FISH) provides an effective means to
      delineate chromosomes and their subregions during all stages of the cell cycle.
      This makes FISH particularly useful for studying chromosome behavior in species
      with minute genomes and/or poor chromosome condensation at metaphase, which is
      the case in model organisms such as the budding yeast Saccharomyces cerevisiae.
      Since its introduction in 1992, FISH with composite whole chromosome or locus
      specific probes has become an indispensable tool in the analysis of chromosome
      behavior in metaphase and interphase cells, and especially of meiotic chromosome
      pairing of wild-type and mutant yeast strains.

PMID- 20809328
TI  - FISH on chromosomes derived from the snail model organism Biomphalaria glabrata.
AB  - The application of fluorescence in situ hybridization (FISH) for the mapping of
      single copy genes onto homologous chromosome has been integral to vast number
      genome sequencing projects, such as that of mouse and human. The chromosomes of
      these organisms are well-studied and are the staple resource of most of the early
      studies conducted in cytogenetics. However, there are now protocols for analyzing
      FISH probes in a number of different organisms on both metaphase and interphase
      chromosomes.Here, we describe the methodologies for the chromosomal mapping of
      nonrepetitive (single-copy) genes of the snail Biomphalaria glabrata onto
      metaphase chromosomes derived from the only molluscan cell-line in existence. The
      technique described in this chapter was developed for the B. glabrata genome
      sequencing project through troubleshooting experimental procedures established
      for other organisms so that both the optimum resolution of metaphase chromosome
      and the effective hybridization of genes were achieved.

PMID- 20809329
TI  - Fluorescence in situ hybridization with Bacterial Artificial Chromosomes (BACs)
      to mitotic heterochromatin of Drosophila.
AB  - The organization of eukaryotic chromosomes into euchromatin and heterochromatin
      represents an enigmatic aspect of genome evolution. Constitutive heterochromatin
      is a basic, yet still poorly understood component of eukaryotic genomes and its
      molecular characterization by means of standard genomic approaches is
      intrinsically difficult. Drosophila melanogaster polytene chromosomes do not seem
      to be particularly useful to map heterochromatin sequences because the typical
      features of heterochromatin, organized as it is into a chromocenter, limit
      cytogenetic analysis. In contrast, constitutive heterochromatin has been well
      defined at the cytological level in mitotic chromosomes of neuroblasts and has
      been subdivided into several bands with differential staining properties.
      Fluorescence in situ hybridization (FISH) using Bacterial Artificial Chromosomes
      (BAC) probes that carry large genomic portions defined by sequence annotation has
      yielded a "revolution" in the field of cytogenetics because it has allowed the
      mapping of multiple genes at once, thus rendering constitutive heterochromatin
      amenable to easy and fast cytogenetics analyses. Indeed, BAC-based FISH
      approaches on Drosophila mitotic chromosomes have made it possible to correlate
      genomic sequences to their cytogenetic location, aiming to build an integrated
      map of the pericentric heterochromatin. This chapter presents our standard
      protocols for BAC-based FISH, aimed at mapping large chromosomal regions of
      mitotic heterochromatin in Drosophila melanogaster.

PMID- 20809330
TI  - Three-dimensional fluorescence in situ hybridization in mouse embryos using
      repetitive probe sequences.
AB  - A common problem in research laboratories that study the mammalian embryo is the
      limited supply of live material. For this reason, new methods are constantly
      being developed and existing methods for in vitro models using cells in culture
      are being adapted to represent embryogenesis. Three-dimensional fluorescence in
      situ hybridization (3D-FISH) is an important tool to study where genomic
      sequences are positioned within nuclei without interfering with this 3D
      organization. When used in the embryo, this technique provides vital information
      about the distribution of specific sequences in relation to embryonic nuclear
      substructures such as nucleolar precursor bodies and chromocenters. In this
      chapter, we will present a detailed description of FISH in order to perform 3D
      FISH in the early preimplantation murine embryos.

PMID- 20809331
TI  - Fluorescence in situ hybridization (FISH) for genomic investigations in rat.
AB  - This chapter concentrates on the use of fluorescence in situ hybridization (FISH)
      for genomic investigations in the laboratory rat (Rattus norvegicus). The
      selection of protocols included in the chapter has been inspired by a
      comprehensive range of previously published molecular cytogenetic studies on this
      model organism, reporting examples of how FISH can be applied for diverse
      investigative purposes, varying from comparative gene mapping to studies of
      chromosome structure and genome evolution, to characterization of chromosomes
      aberrations as well as transgenic insertions. The protocols, which include
      techniques for the preparation of mitotic chromosomes and DNA fibers from short
      term cell cultures, have been gathered through the years and repeatedly tested in
      our laboratory, and all together aim at providing sufficient experimental
      versatility to cover a broad range of cytogenetic and cytogenomic applications.

PMID- 20809332
TI  - Fluorescence in situ hybridization on early porcine embryos.
AB  - Insight into the normal and abnormal function of an interphase nucleus can be
      revealed by using fluorescence in situ hybridization (FISH) to determine
      chromosome copy number and/or the nuclear position of loci or chromosome
      territories. FISH has been used extensively in studies of mouse and human early
      embryos, however, translation of such methods to domestic species have been
      hindered by the presence of high levels of intracytoplasmic lipid in these
      embryos which can impede the efficiency of FISH. This chapter describes in detail
      a FISH protocol for overcoming this problem. Following extensive technical
      development, the protocol was derived and optimized for IVF porcine embryos to
      enable investigation of whole chromosome and subchromosomal regions by FISH
      during these early stages of development. Porcine embryos can be generated in
      vitro using semen samples from commercial companies and oocytes retrieved from
      discarded abattoir material. According to our method, porcine embryos are lyzed
      and immobilized on slides using Hydrochloric acid and "Tween 20" detergent, prior
      to pretreatment with RNase A and pepsin before FISH. The method described has
      been optimized for subsequent analysis of FISH in two dimensions since organic
      solvents, which are necessary to remove the lipid, have the effect of flattening
      the nuclear structure. The work in this chapter has focussed on the pig; however,
      such methods could be applied to bovine, ovine, and canine embryos, all of which
      are rich in lipid.

PMID- 20809333
TI  - FISH on 3D preserved bovine and murine preimplantation embryos.
AB  - Fluorescence in situ hybridization (FISH) is a commonly used technique for the
      visualization of whole chromosomes or subchromosomal regions, such as chromosome
      arms, bands, centromeres, or single gene loci. FISH is routinely performed on
      chromosome spreads, as well as on three-dimensionally preserved cells or tissues
      (3D FISH). We have developed 3D FISH protocol for mammalian preimplantation
      embryos to investigate the nuclear organization of chromosome territories and
      subchromosomal regions during the first developmental stages. In contrast to
      cells, embryos have much more depth and their nuclei are therefore less
      accessible to probes used to visualize specific genomic regions by FISH. The
      present protocol was developed to establish a balance between sufficient embryo
      permeabilization and maximum preservation of nuclear morphology.

PMID- 20809334
TI  - Wnt/beta-Catenin pathway in human glioma: expression pattern and
      clinical/prognostic correlations.
AB  - Gliomas are the most common primary intracranial tumors. Understanding the
      molecular basis of gliomas' progression is required to develop more effective
      therapies. The Wnt/beta-catenin signaling cascade is an important signal
      transduction pathway in human cancers. Although, overactivation of this pathway
      is a hallmark of several forms of cancer, little is known about its role in human
      gliomas. Here, we aimed to determine the clinical significance of Wnt/beta
      catenin pathway components in gliomas. Immunohistochemical staining was performed
      to detect the expression patterns of Wnt1, beta-catenin and Cyclin D1 in the
      biopsies from 96 patients with primary gliomas. Kaplan-Meier survival and Cox
      regression analyses were performed to evaluate the prognosis of patients.
      Cytoplasmic staining pattern of Wnt1, membranous, cytoplasmic and nuclear
      accumulation of beta-catenin, and nuclear localization of Cyclin D1 were
      demonstrated by immunohistochemical staining. The Wnt1 expression significantly
      correlated with the expression of Cyclin D1 (P < 0.0001). The ratio of tumors
      with a cytoplasmic-nuclear pattern or a cytoplasmic pattern of beta-catenin was
      significantly higher in Wnt1-positive (P < 0.01) and Cyclin D1-positive (P <
      0.01) tumors than in Wnt1-negative and Cyclin D1-negative tumors, respectively.
      The protein expression levels of Wnt1, beta-catenin and Cyclin D1 were all
      positively correlated with the Karnofsky performance scale (KPS) score and World
      Health Organization (WHO) grades of patients with gliomas. Furthermore, Wnt1,
      cytoplasmic-nuclear beta-catenin and Cyclin D1 status were all the independent
      prognostic factors for glioma patients (P = 0.01, 0.007 and 0.005, respectively).
      These results provide convincing evidence that the Wnt/beta-catenin pathway
      correlated closely with the progression of gliomas and might be a novel
      prognostic marker for this neoplasm.

PMID- 20809335
TI  - Molecular markers in gliomas: impact for the clinician.
AB  - Over the last decade, understanding of glioma on a molecular level has greatly
      expanded. However, optimal incorporation of molecular markers into clinical care
      is controversial. We briefly review the potential utility of molecular
      stratification in refining histologic diagnosis, prognosis, and treatment
      decisions, focussing on 1p/19q co-deletion, MGMT promoter methylation, EGFR
      mutations, and IDH mutation. The most recently discovered IDH mutation is a
      striking example of a rapid implementation of a molecular marker for
      prognostication into common clinical use.

PMID- 20809336
TI  - Occupational problems with microscopy in the pathology laboratory.

PMID- 20809337
TI  - Androgen receptor is frequently expressed in HER2-positive, ER/PR-negative breast
      cancers.
AB  - The estrogen receptor (ER)/progesterone receptor (PR)-negative breast carcinomas
      (BCs) encompass three molecular subtypes: one with human epidermal growth factor
      receptor 2 (HER) overexpression, one normal like, and the triple negative. The
      androgen receptor (AR) is expressed in 70-90% of invasive BCs. The aim of our
      study is to detect the expression of AR in a series of ER/PR-negative BCs to
      ascertain if there is clinical significance in relation to BC molecular subtypes.
      A immunohistochemical study for all receptors and cytokeratin expression was
      performed in 232 cases of ER/PR-negative BCs. According to cytokeratin
      expression, BCs were classified into two groups: luminal-type BCs (44.2%) and
      basal-like-type BCs (55.8%). According to the expression of HER2, 59.3% were
      triple-negative BCs (when ER, PR, and HER2 were negative) and 40.7% were HER2
      positive BCs. AR expression was observed in 128 tumors (56.6%). One hundred and
      ten cases (48.8%) had >10% and 18 (7.8%) had <10% of positively stained cells. AR
      immunoreactivity was found in 31.2% basal-like BCs, while in the luminal group
      71.1% of cases were positive, showing highly significant correlation (p < 10-8).
      Regarding HER2 status, 76.7% of HER2-positive BC cases were AR positive compared
      with only 30.4% of triple-negative BC types, showing a strong statistically
      significant correlation. In conclusion, we show that AR is frequently expressed
      in ER/PR-negative BCs and that expression of HER2 and AR is highly correlated (p
      < 0.005). Our results point out the role of AR and HER2 in the pathogenesis of
      BCs and suggest the potential role of AR in clinical management of ER/PR-negative
      BCs.

PMID- 20809338
TI  - Differences in the T-bet and GATA-3 expression patterns between lymphocytic
      colitis and coeliac disease.
AB  - Lymphocytic colitis (LC) is a disease of unknown aetiology. Among other
      pathogenetic possibilities, an abnormal reaction to a luminal antigen has been
      discussed. To clarify this fact, we characterized the inflammatory infiltrate in
      LC and compared it with the Th1 response-related coeliac disease (CD). Biopsies
      from 10 LC and 10 CD patients were analyzed by immunohistochemistry for detection
      of T-bet, the master regulator of Th1 response and its antagonist GATA-3 in T
      cells employing double labellings. In LC, 10-20% of intraepithelial lymphocytes
      (IEL) expressed GATA-3 and the remaining T-bet, whereas in CD, all IEL were T-bet
      positive. The T cells in the lamina propria of LC (65-70% CD4+; 30-35% CD8+)
      showed a mixed expression pattern of T-bet and GATA-3. The majority of the CD4+ T
      cells were GATA-3+, while T-bet and GATA-3 were expressed at a similar frequency
      by the CD8+ T cells. Most of the T cells in the lamina propria of CD specimens
      were CD4+, showing a predominant T-bet expression. Also, most of the CD8+ lamina
      propria T cells in CD were T-bet+. We conclude that in contrast to CD, which
      exhibits immunophenotypical features of a Th1-response, LC shows features of a
      mixed Th1/Th2 immune response.

PMID- 20809339
TI  - Assessing environmental and occupational risk factors for lung cancer in Mexican
      Americans.
AB  - BACKGROUND: We investigated environmental and occupational exposures and smoking
      history (while controlling for demographics) in a population of Mexican-American
      lung cancer cases and controls from the Houston metropolitan area. METHODS: Data
      were collected between 1991 and 2005 as part of an on-going multi-racial/ethnic,
      lung cancer case-control study. Cases included 212 Mexican-American lung cancer
      cases from UT MD Anderson Cancer Center. Controls (n = 328) were recruited from
      Houston's largest multispecialty group practice and frequency matched to the
      cases by age (+/- 5 years), sex, and ethnicity. Environmental and occupational
      factors were analyzed and odds ratios and 95% confidence intervals were
      calculated using logistic regression. RESULTS: We detected elevated risks of lung
      cancer associated with pesticide exposure and found conventional and
      antimicrobial (e.g., sterilizers, disinfectants, antiseptics) pesticides were
      associated with an increased risk of lung cancer in Mexican-Americans
      (conventional pesticides and antimicrobial pesticides combined: OR = 1.80, 95% CI
      1.13-2.86; conventional pesticides: OR = 2.05, 95% CI 1.23-2.39; antimicrobial
      pesticides: OR = 2.48, 95% CI 1.46-4.21). CONCLUSIONS: Although we found over a
      two-fold increased risk of lung cancer among Mexican-Americans for pesticides, we
      could not identify individual pesticides. Our findings are an important
      preliminary step in identifying factors that are specifically associated with
      lung cancer risk among Mexican Americans.

PMID- 20809340
TI  - Health issues among foreign born uninsured children visiting an inner city
      pediatric emergency department.
AB  - To study the demographic and socio-economic characteristics of foreign born
      children visiting an inner city pediatric emergency department (PED) and to
      assess their access to care, unmet health care needs, barriers to care and follow
      up care. A cross-sectional study was conducted in October and November 2006;
      parents of children visiting an inner city PED underwent face-to-face interview
      regarding their socio-economic status, access to health care, unmet medical needs
      and barriers to care. A follow-up telephonic interview was conducted within 1
      week of the ED visit to assess compliance with follow-up care. 385 patients (Mean
      age 4.63 years, 51.9% male) were enrolled prospectively. 297 (77%) children had
      health insurance and 88 (23%) were uninsured. 38 (43%) uninsured children were
      foreign born. Of those uninsured, 53 (60%) were uninsured for >a year and 35
      (40%) had been uninsured part year. Compared with insured children, fewer
      uninsured children had a regular place for medical care (89 vs. 46%, P < 0.001),
      a regular Primary Care Provider (95 vs. 68%, P < 0.001), and regular dental care
      (46 vs. 26%, P < 0.001). Almost one-third of parents of uninsured children
      reported a perceived barrier to care (31 vs. 8%, P < 0.001). Uninsured children,
      who were foreign born, were older (mean age 8.9 vs. 4.9 years, P < 0.001),
      primarily Spanish speaking (95 vs. 76%, P < 0.02), poorer, with household income
      less than 100% of the Federal poverty level and had poorer access to care. They
      also used the PED as their primary source of care more frequently (87 vs. 66%, P
      < 0.03). In a multivariate logistic regression analysis, children with no health
      insurance, and those children who were foreign born were more likely to have poor
      access to care with odds ratio (95% CI) of 0.19 (0.08-0.46) and 0.35 (0.13-0.95),
      respectively. CONCLUSIONS: Significant proportions of uninsured children visiting
      our PED are born in Mexico and from low income immigrant families, many do not
      qualify for public insurance, have poor access to care, and use the PED for their
      healthcare needs. This is likely to be a growing problem in certain regions of
      the country requiring targeted health policy intervention.

PMID- 20809341
TI  - About hierarchical log linear analysis of admission blood parameters and clinical
      outcome following traumatic brain injury.

PMID- 20809342
TI  - Application of imaging guidelines in patients with suspected cervical spine
      trauma: retrospective analysis and literature review.
AB  - Safe and efficient clearance of cervical spine injury in blunt trauma patients
      has been a controversial topic among health professionals. The increased
      availability of CT scanners in major trauma centers seems to be a factor that has
      led to increased number of unnecessary cervical spine imaging using this imaging
      modality. The objective of this study was to investigate the applicability and
      efficacy of a pre-test clinical criterion in order to stratify post-blunt trauma
      victims based on their risk of sustaining cervical spine injury and in turn
      recommend an appropriate imaging modality accordingly. Goergen's criteria
      (Australas Radiol 48(3):287, 2004), a pre-investigation diagnostic algorithm was
      retrospectively applied to 106 blunt trauma victims who presented to a level 1
      trauma center in Sydney, Australia, and had a CT scan of cervical spine as part
      of their initial management. Overall, nine (8.5%) of patients sustained a
      significant cervical spine injury. All nine patients would be classified as high
      risk victims according to the algorithm investigated in this study, warranting CT
      scanning. No patients with low-risk injuries were demonstrated to have a
      significant cervical spine injury. There was a statistically significant greater
      proportion of acute cervical spine injuries detected in the high-risk group (p
      value = 0.0024). Hence, using Goergen's diagnostic algorithm could reduce the
      number of unnecessary cervical spine CT scans ordered, while not compromising the
      quality of care in post-blunt trauma victims.

PMID- 20809343
TI  - Two cases of ruptured cerebral aneurysms presenting with contralateral hematomas.
AB  - We present two cases of hematoma contralateral to the aneurysm. Case 1 is a 62
      year-old woman presenting with a large left frontal intraparenchymal hematoma
      (IPH) and a right posterior communicating artery (PCoA) aneurysm. This is the
      first reported case of a contralateral frontal IPH from PCoA aneurysm rupture.
      Case 2 is a 58-year-old male with right PCoA aneurysm and left sylvian SAH. Both
      patients underwent coil embolization of offending lesions, with repeat angiograms
      revealing no other vascular anomalies.

PMID- 20809344
TI  - Occurrence of synthetic musks in indoor dust from China and implications for
      human exposure.
AB  - Synthetic musk compounds are used in a wide range of personal care and other
      consumer products. Despite this fact, few studies have reported the occurrence of
      synthetic musks in house dust or exposure of humans through the ingestion of
      indoor dust. In the present study, we determined the concentrations and profiles
      of two polycyclic musks (PCMs; Galaxolide((r)) [HHCB] and Tonalide((r))), three
      nitro musks (NMs; musk ketone [MK], musk moskene [MM], and musk xylene [MX]), and
      one metabolite of HHCB (HHCB-lactone), in 88 indoor-dust samples from homes,
      dormitories, offices, and laboratories in China. In addition, we analyzed 12 dust
      samples collected from inside the housings of electrical/electronic devices that
      were located in 10 of the houses. Synthetic musks were detected in all of the
      dust samples analyzed, with total concentrations (sum of PCM and NM
      concentrations) varying from 4.42 to 688 ng g-1 (mean +/- SD: 126 +/- 16.2 ng g
      1; median: 82.7 ng g-1). HHCB was the predominant compound in all of the dust
      samples analyzed accounting on average for 42.2% of the total musk
      concentrations. Concentrations of synthetic musks in dust samples from homes and
      offices were higher than the concentrations found in samples from dormitories and
      laboratories. Concentrations of synthetic musks in dust samples increased with
      the increasing number of occupants in homes. Based on the concentrations, levels
      of exposure to musks by way of dust ingestion were calculated to be up to 25.8 ng
      d-1 for adults and 138 ng d-1 for toddlers.

PMID- 20809345
TI  - Influence of a toxic Microcystis aeruginosa strain on glutathione synthesis and
      glutathione-S-transferase activity in common carp Cyprinus carpio (Teleostei:
      Cyprinidae).
AB  - We evaluated the effects of aqueous extracts of the cyanobacterium-producing
      microcystin (MC), Microcystis aeruginosa (strain RST9501), on detoxification
      capacity and glutathione (GSH) synthesis in liver, brain, gill, and muscle-as
      well as apoptotic protease (calpain) activity in liver and brain-in the common
      carp Cyprinus carpio (Teleostei: Cyprinidae). Experimental groups were defined as
      follows: (1) control (CTR); (2) carp treated with an aqueous extract from the
      toxic cyanobacteria M. aeruginosa in a final MC concentration of 25 MUg/kg (MC
      25); and (3) carp treated with an aqueous extract from the toxic cyanobacteria M.
      aeruginosa in a final MC concentration of 50 MUg/kg (MC 50). Carp were gavaged
      with a cyanobacterial aqueous solution or MilliQ water (CTR group). The
      experiment was conducted for period of 48 h comprising two gavages with a 24-h
      interval between them. Some of the parameters analyzed in liver, brain, gill, and
      muscle included activity of the enzymes glutathione-S-transferase (GST),
      glutamate cysteine ligase (GCL), glutathione reductase (GR), and GSH
      concentration. We also evaluated GST pi concentration by Western blot as well as
      calpain activity in liver and brain samples. In carp liver from the MC 50 group,
      we observed a decrease in GST and GCL activity, which was accompanied by a
      decreased GSH concentration. In addition, liver calpain activity was highly
      induced in carp at both MC doses. Thus, MC ingestion affected the liver
      antioxidant status through decreasing the GSH concentration and the activity of
      the enzyme involved in its synthesis (GCL). It also decreased the MC
      detoxification capacity of the liver because total GST activity decreased, a
      result that cannot be ascribed to GST pi levels. Because GSH acts as an
      uncompetitive inhibitor of calpain, its decrease should explain the higher
      activity of this apoptotic enzyme. The main goal of this study was to show that a
      decrease in GSH concentration is related to decreased activity of GCL, the
      limiting enzyme involved in GSH synthesis. Because MCs are phosphatase inhibitors
      and GCL is allosterically inhibited by phosphorylation, the cellular
      hyperphosphorylation state induced by MC exposure could act as a modulator factor
      for antioxidant defenses.

PMID- 20809346
TI  - Striatal dopamine function in a family with multiple SCA-3 phenotypes.
AB  - We present single photon emission computed tomography (SPECT) studies using
      123IFP-CIT (DAT scan) and 123I-IBZM imaging, performed on four members of a
      family with genetically proven spinocerebellar ataxia type 3 (SCA-3). DAT scan
      showed significant asymmetric decreased binding in the striatum in the two
      members with predominant parkinsonian phenotype, with mild and symmetric
      decreased binding in the member with the cerebellar phenotype, and normal in the
      asymptomatic member. The IBZM SPECT studies showed mild and asymmetrical
      reduction of the striatal dopamine D2 receptor density (parkinsonian members).
      SCA-3 can present with a levodopa responsive parkinsonism phenotype, and an
      abnormal DAT scan showing predominant impairment of presynaptic dopamine
      function.

PMID- 20809348
TI  - Knowledge, attitudes, and behaviors of health, education, and service
      professionals as related to fetal alcohol spectrum disorders.
AB  - OBJECTIVES: We explored differences in fetal alcohol spectrum disorders (FASD)
      knowledge, attitudes, and behaviors across six groups of professionals in key
      position to provide primary and secondary prevention efforts (physicians,
      educators, correctional staff, social workers, public health nurses, and
      substance abuse counselors). METHODS: Achieving a 60.1% response rate, 2,292
      professionals returned surveys, providing data on basic knowledge of FAS, FASD
      associated risks and cognitive deficits, and willingness to confront and
      recommend treatment to alcohol-consuming pregnant women. RESULTS: Across groups,
      findings revealed ample FASD knowledge and willingness to confront and recommend
      treatment to alcohol-consuming pregnant women that increases as consumption
      becomes more frequent and severe. However, results revealed significant between
      group differences data that provide valuable guidance for targeted future FASD
      education efforts. CONCLUSIONS: Public health initiatives regarding FASD have
      been effective in increasing knowledge among a broad range of professionals.
      However, between-group differences indicate the need for targeted, discipline
      specific interventions. These differences highlight the need for all professional
      groups to provide a consistent public health message regarding maternal alcohol
      consumption.

PMID- 20809349
TI  - Interviewer gender and self-reported sexual behavior and mental health among male
      military personnel.
AB  - OBJECTIVES: To determine whether self-reported sexual behavior and mental health
      varied by interviewer gender in a population of male military personnel. METHODS:
      Eight male and six female data collectors verbally administered structured
      interviews to 474 male Dominican military personnel stationed at border crossing
      zones in the Dominican Republic. Measurements included sexual behaviors and
      mental health. RESULTS: Respondents were less likely to report oral and vaginal
      sex to male interviewers, and were more likely to report sexual coercion and
      alcohol abuse to male interviewers. Respondents were more likely to report
      depression and post-traumatic stress disorder to female interviewers. CONCLUSION:
      Interviewer gender influenced the prevalence of sexual behaviors and mental
      health, which carries implications for future research in military personnel.

PMID- 20809350
TI  - Traditional versus single-site placement of adjustable gastric banding: a
      comparative study and cost analysis.
AB  - In bariatric surgery, laparoscopic adjustable gastric banding (LAGB) has proven
      effective in reducing weight and improving obesity-associated comorbidities.
      Recently, however, laparoendoscopic single-site (LESS) surgery has been proposed
      to minimize the invasiveness of laparoscopic surgery. The aim of this study is to
      compare the operative cost and peri-operative outcomes of these two approaches.
      We undertook a retrospective review of a prospectively maintained database of
      patients undergoing either LAGB or LESS between March 2006 and October 2009. The
      outcomes and cost of 25 LESS gastric bandings were compared to 121 standard LAGB.
      Costs included operative time, consumables, and laparoscopic tower depreciation.
      Both groups had similar patient demographics, body mass index, and comorbidities;
      with the exception of age (37 year for single site vs. 44 years for standard;
      P=0.002). There were no statistical differences for operative time (78 vs. 76
      min, P=0.69), blood loss (8.4 vs. 9 ml, P=0.76), pain score (0.81 vs. 0.84 at 1
      week, P=0.95) or complication rates (12% vs. 14%, P=1). Length of stay was
      shorter for the LESS group (0.5 day vs. 1.5 days, P=0.02). The mean operative
      cost for the LESS banding was $20,502/case vs. $20,346/case for the standard
      LAGB, with no statistically significant difference between the approaches
      (P=0.73). Operative costs and peri-operative outcomes of LESS gastric banding are
      comparable with those of the standard LAGB procedure. As a result, single-site
      surgery can be proposed as a valid alternative to the standard procedure with
      cosmetic advantage and comparable complication rate.

PMID- 20809351
TI  - How to achieve synergy between medical education and cognitive neuroscience? An
      exercise on prior knowledge in understanding.
AB  - A major challenge in contemporary research is how to connect medical education
      and cognitive neuroscience and achieve synergy between these domains. Based on
      this starting point we discuss how this may result in a common language about
      learning, more educationally focused scientific inquiry, and multidisciplinary
      research projects. As the topic of prior knowledge in understanding plays a
      strategic role in both medical education and cognitive neuroscience it is used as
      a central element in our discussion. A critical condition for the acquisition of
      new knowledge is the existence of prior knowledge, which can be built in a mental
      model or schema. Formation of schemas is a central event in student-centered
      active learning, by which mental models are constructed and reconstructed. These
      theoretical considerations from cognitive psychology foster scientific
      discussions that may lead to salient issues and questions for research with
      cognitive neuroscience. Cognitive neuroscience attempts to understand how
      knowledge, insight and experience are established in the brain and to clarify
      their neural correlates. Recently, evidence has been obtained that new
      information processed by the hippocampus can be consolidated into a stable,
      neocortical network more rapidly if this new information fits readily into a
      schema. Opportunities for medical education and medical education research can be
      created in a fruitful dialogue within an educational multidisciplinary platform.
      In this synergetic setting many questions can be raised by educational scholars
      interested in evidence-based education that may be highly relevant for
      integrative research and the further development of medical education.

PMID- 20809352
TI  - Species abundance distributions in neutral models with immigration or mutation
      and general lifetimes.
AB  - We consider a general, neutral, dynamical model of biodiversity. Individuals have
      i.i.d. lifetime durations, which are not necessarily exponentially distributed,
      and each individual gives birth independently at constant rate lambda. Thus, the
      population size is a homogeneous, binary Crump-Mode-Jagers process (which is not
      necessarily a Markov process). We assume that types are clonally inherited. We
      consider two classes of speciation models in this setting. In the immigration
      model, new individuals of an entirely new species singly enter the population at
      constant rate MU (e.g., from the mainland into the island). In the mutation
      model, each individual independently experiences point mutations in its germ
      line, at constant rate theta. We are interested in the species abundance
      distribution, i.e., in the numbers, denoted I(n)(k) in the immigration model and
      A(n)(k) in the mutation model, of species represented by k individuals, k = 1, 2,
      . . . , n, when there are n individuals in the total population. In the
      immigration model, we prove that the numbers (I(t)(k); k >= 1) of species
      represented by k individuals at time t, are independent Poisson variables with
      parameters as in Fisher's log-series. When conditioning on the total size of the
      population to equal n, this results in species abundance distributions given by
      Ewens' sampling formula. In particular, I(n)(k) converges as n -> infinity to a
      Poisson r.v. with mean gamma/k, where gamma : = MU/lambda. In the mutation model,
      as n -> infinity, we obtain the almost sure convergence of n (-1) A(n)(k) to a
      nonrandom explicit constant. In the case of a critical, linear birth-death
      process, this constant is given by Fisher's log-series, namely n(-1) A(n)(k)
      converges to alpha(k)/k, where alpha : = lambda/(lambda + theta). In both models,
      the abundances of the most abundant species are briefly discussed.

PMID- 20809354
TI  - Impact of psychotherapy on insomnia symptoms in patients with depression and
      multiple sclerosis.
AB  - The purpose of the study was to evaluate the prevalence of insomnia in multiple
      sclerosis patients with comorbid depression, associations between psychological
      symptoms, multiple sclerosis symptoms and insomnia, and to test effects of a 16
      week protocol-based psychotherapy intervention for depression on insomnia
      symptoms. Participants with multiple sclerosis and depression (n = 127) were
      randomized to telephone administered cognitive behavioral therapy and telephone
      administered supportive emotion-focused therapy. Multiple sclerosis functional
      limitation was measured at baseline. Depression, insomnia, anxiety and quality of
      life were evaluated at pre treatment, mid treatment (8 weeks), and post treatment
      (16 weeks). Prevalence of insomnia >=3 times per week was 78% at pre treatment
      and 43% at post treatment. Insomnia at baseline was associated with depression,
      multiple sclerosis related mood symptoms and anxiety. Middle of the night
      awakenings were associated with swallowing and speech problems. Improvements in
      insomnia were associated with improvement in depression and anxiety. Participants
      with residual insomnia were more likely to have major depressive disorder,
      greater multiple sclerosis severity, elevated anxiety and lower mental components
      of quality of life. Results demonstrate rates of insomnia in patients with
      comorbid multiple sclerosis and depression are higher than those reported in the
      general multiple sclerosis population and additional insomnia treatment is
      indicated beyond the treatment of comorbid psychological disorders.

PMID- 20809353
TI  - Evolution of enzymatic activities of testis-specific short-chain
      dehydrogenase/reductase in Drosophila.
AB  - The testis-specific gene Jingwei (jgw) is a newly evolved short-chain
      dehydrogenase/reductase in Drosophila. Preliminary substrate screening indicated
      that JGW prefers long-chain primary alcohols as substrates, including several
      exotic alcohols such as farnesol and geraniol. Using steady-state kinetics
      analyses and molecular docking, we not only confirmed JGW's substrate
      specificity, but also demonstrated that the new enzymatic activities of JGW
      evolved extensively after exon-shuffling from a preexisting enzyme. Analysis of
      JGW orthologs in sister species shows that subsequent evolutionary changes
      following the birth of JGW altered substrate specificities and enzyme
      stabilities. Our results lend support to a general mechanism for the evolution of
      a new enzyme, in which catalytic chemistry evolves first followed by
      diversification of substrate utilization.

PMID- 20809356
TI  - Viral DNA contamination is responsible for Epstein-Barr virus detection in
      cytotoxic T lymphocytes stimulated in vitro with Epstein-Barr virus B
      lymphoblastoid cell line.
AB  - Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell lines (LCLs) are used
      to prepare human EBV-specific T lymphocytes (EBV-CTL) in vitro. Within an LCL, up
      to 5-7% the cells release infectious EBV, and this has fostered safety concerns
      for therapeutic applications because of the exposure of T cells to EBV. The
      release of infectious viruses can be prevented by ganciclovir, but this drug may
      seriously affect LCL growth. In the wake of these concerns, the present work was
      designed to compile safety data on EBV-CTL preparation for the purpose of
      submission to a regulatory agency. We showed that further to supernatant
      exclusion, the number of EBV genome copies (EBVc) associated with the EBV-CTL
      always made up a constant proportion of the EBVc number detected in the culture
      supernatant. In addition, such was the case whether infectious virus could be
      produced by the LCL or not, suggesting that the EBV signal detected was due to a
      DNA contamination rather than an infection. Furthermore, we demonstrated that the
      number of EBVc associated with the EBV-CTL was highly sensitive to DNAse
      treatment, and finally that EBVc could no longer be detected after the EBV-CTL
      had been amplified in the absence of LCL. Consequently, during in vitro EBV-CTL
      preparation, either T cells cannot be infected or they die rapidly after EBV
      infection.

PMID- 20809355
TI  - Personal attributions for melanoma risk in melanoma-affected patients and family
      members.
AB  - Personal attributions for cancer risk involve factors that individuals believe
      contribute to their risk for developing cancer. Understanding personal risk
      attributions for melanoma may dictate gene-environment melanoma risk
      communication strategies. We examined attributions for melanoma risk in a
      population-based sample of melanoma survivors, first degree family members, and
      family members who are also parents (N = 939). We conducted qualitative
      examination of open-ended risk attributions and logistic regression examining
      predictors (demographics, family member type, perceived risk) of the attributions
      reported (ultraviolet radiation [UVR] exposure, heredity/genetics, phenotype,
      personal melanoma history, miscellaneous). We found a predominance of risk
      attributions to UVR and heredity/genetics (80 and 45% of the sample,
      respectively). Those reporting higher education levels were more likely to
      endorse attributions to heredity/genetics, as well as to phenotype, than those of
      lower education levels. First-degree relatives and parent family members were
      more likely to endorse heredity/genetic attributions than melanoma survivors;
      melanoma survivors were more likely to endorse personal history of melanoma
      attributions compared to first-degree relatives and parent family members. These
      findings inform the development of risk communication interventions for melanoma
      families.

PMID- 20809357
TI  - Evaluation of the immunogenicity of a single chain chimeric peptide composed of
      hCGbeta and oLHalpha for inhibition of the growth of hCGbeta-expressing cancer
      cells.
AB  - Human chorionic gonadotropin (hCG) is a membrane-associated protein highly
      expressed in several types of human cancer cells. The expression in the cancer
      cells indicates that hCG may be a potential target molecule for cancer
      immunotherapy. The objective of this study was to develop a novel immunogenic
      molecule, which can efficiently induce the neutralizing antibody against hCG and
      which is also suitable for mass production. The immunogenicity of the recombinant
      single chain chimeric protein of hCGbeta-oLHalpha expressed by yeast was
      examined. Additionally, the inhibitory effects of the anti-hCGbeta-oLHalpha
      antibody on the growth of hCG-positive cancer cells were determined. It was found
      that hCGbeta-oLHalpha yielded high titers of anti-hCG rabbit antibody that could
      effectively neutralize the bioactivity of hCG. The rabbit anti-hCGbeta-oLHalpha
      IgG inhibited the proliferation of hCG-expressing human colorectal cancer cells
      (LS-174, HCT-116, HCT-15 and KM-12) in a dose-dependent manner. Furthermore, an
      intact anti-tumor vaccine was prepared by conjugating hCGbeta-oLHalpha with
      tetanus toxoid (TT) and this was used to immunize Balb/c mice bearing hCG
      expressing SP2/0 tumor cells. The progression of tumors in these immunized mice
      was remarkably inhibited. These results suggest that hCGbeta-oLHalpha is a new
      promising immunogenic molecule for the development of an anti-hCG-based cancer
      vaccine.

PMID- 20809358
TI  - Association between mitogen-activated protein kinase kinase kinase 1 rs889312
      polymorphism and breast cancer risk: evidence from 59,977 subjects.
AB  - Published data on the association between mitogen-activated protein kinase kinase
      kinase 1 (MAP3K1) gene rs889312 polymorphism and breast cancer risk are
      inconclusive. To derive a more precise estimation of the relationship, a meta
      analysis was performed. Crude ORs with 95% CIs were used to assess the strength
      of association between them. A total of seven eligible articles including 26,015
      cases and 33,962 controls based on the search criteria were involved in this meta
      analysis. We observed that the MAP3K1 rs889312 polymorphism was significantly
      correlated with breast cancer risk from the fixed effects model when all studies
      were pooled into the meta-analysis (the allele contrast model: OR 1.09, 95% CI
      1.07-1.12; the homozygote codominant: OR 1.22, 95% CI 1.15-1.29; the heterozygote
      codominant: OR 1.07, 95% CI 1.04-1.11; the dominant model: OR 1.10, 95% CI 1.06
      1.13; the recessive model: OR 1.18, 95% CI 1.12-1.25). No significant association
      was found in the BRCA1 mutation carriers in all genetic models. When stratified
      by BRCA2 mutation carriers status, statistically significantly elevated risk was
      found in this meta-analysis (C vs. A: OR 1.12, 95% CI 1.01-1.23; CC vs. AA: OR
      1.35, 95% CI 1.06-1.71; the recessive model: OR 1.31, 95% CI 1.05-1.65). There
      was no evidence for significant association between MAP3K1 rs889312 polymorphism
      and breast cancer risk in BRCA1 and BRCA2 positive cohort for all comparison
      models. In conclusion, this meta-analysis suggests that the MAP3K1 rs889312 C
      allele is a low-penetrant risk factor for developing breast cancer, and there is
      limited evidence to indicate that MAP3K1 rs889312 polymorphism is associated with
      increased risk of breast cancer in BRCA1 mutation carriers.

PMID- 20809359
TI  - Glutathione S-transferase P1 Ile105Val polymorphism and breast cancer risk:
      convergence and divergence of the two recent meta-analyses.

PMID- 20809360
TI  - Oral fluoropyrimidine may augment the efficacy of aromatase inhibitor via the
      down-regulation of estrogen receptor in estrogen-responsive breast cancer
      xenografts.
AB  - The present preclinical study was designed to evaluate a new combination therapy
      comprised of the aromatase inhibitor anastrozole (ANA) and the oral
      fluoropyrimidines, UFT and S-1 against the estrogen receptor (ER)-positive human
      breast cancer cell line MCF-7/Arom 14, which was stably transfected with the cDNA
      of human aromatase. MCF-7/Arom 14 cells showed a high aromatase activity and
      notably were able to grow in the presence of testosterone and estradiol (E(2)) in
      vitro. ANA and 5-fluorouracil (5-FU) inhibited cell growth at concentrations of
      0.005-10 and 0.2-5 MUM, respectively, and the combination of both drugs
      additively inhibited cell growth. The growth of MCF-7/Arom 14 tumors was
      significantly inhibited by ANA and S-1 or UFT in vivo. The combination of ANA
      with S-1 or UFT administered using a 21-day consecutive, metronomic-like regimen
      significantly enhanced the antitumor efficacy, suppressing tumor growth for 2-4
      times longer than monotherapy. To investigate the mechanisms by which S-1
      enhances the antitumor activity of ANA, the protein and mRNA expression levels of
      ER-alpha in tumor tissue after treatment with S-1, ANA, and the typical
      chemotherapeutic agents doxorubicin (ADM) or paclitaxel (TXL) were analyzed. The
      protein and mRNA expression levels of ER-alpha in the tumor tissue were markedly
      decreased after treatment with S-1 or S-1 + ANA, but not after treatment with
      either ADM or TXL. The reduced ER-alpha level after S-1 treatment might
      contribute to the increased antitumor activity of ANA by reducing ER-alpha
      induced growth signaling in addition to the decrease in estrogen production
      induced by ANA. Based on these results, the combination of ANA and S-1 might
      yield a greater benefit than other chemotherapeutic agents in postmenopausal
      women with ER-positive breast cancer.

PMID- 20809361
TI  - Fertility drugs and the risk of breast cancer: a meta-analysis and review.
AB  - The risk of breast cancer has been associated with reproductive history. The
      purpose of this study was to determine the relationship between fertility drugs
      used in assisted reproductive procedures and the risk of breast cancer. We
      performed a literature search using the MEDLINE, the COCHRANE Library, and Scopus
      to identify studies linking breast cancer to fertility drugs. We excluded case
      series, case reports, and review articles from our analysis. The study
      populations included women who were treated for infertility with clomiphene,
      gonadotropins, gonadotropin-releasing hormones, or other unspecified fertility
      agents. We extracted information on study design, sample size, type of fertility
      drugs and number of treatment cycles, breast cancer incidence, and follow-up time
      from these studies. Eight case-control studies and fifteen cohort studies were
      included in the quantitative analyses. The Newcastle-Ottawa Quality Assessment
      Scales were used. Two investigators independently extracted study methods,
      sources of bias, and outcomes. We found that the risk of breast cancer was not
      significantly associated with fertility drug treatment. The follow-up periods
      were short in some of the studies analyzed in our study; however, we proceeded to
      test the trend in risk estimates across different durations of follow-up and
      found a trend for association using the nonparametric test; this was interpreted
      with caution in view of the lack of adjustment with other confounding factors.
      The current published data do not suggest higher risk of breast cancer in women
      who receive fertility treatment, but the lack of long-term follow up and the
      inherent weaknesses in some of the published studies have to be cautiously taken
      into account.

PMID- 20809362
TI  - Comprehensive CYP2D6 genotype and adherence affect outcome in breast cancer
      patients treated with tamoxifen monotherapy.
AB  - The association between CYP2D6 genotype and outcome in breast cancer patients
      treated with adjuvant tamoxifen remains controversial. We assessed the influence
      of comprehensive versus limited CYP2D6 genotype in the context of tamoxifen
      adherence and co-medication in a large cohort of 618 patients. Genotyping of 33
      CYP2D6 alleles used two archival cohorts from tamoxifen-treated women with
      invasive breast cancer (Dundee, n = 391; Manchester, n = 227). Estimates for
      recurrence-free survival (RFS) were calculated based on inferred CYP2D6
      phenotypes using Kaplan-Meier and Cox proportional hazard models, adjusted for
      nodal status and tumour size. Patients with at least one reduced function CYP2D6
      allele (60%) or no functional alleles (6%) had a non-significant trend for worse
      RFS: hazard ratio (HR) 1.52 (CI 0.98-2.36, P = 0.06). For post-menopausal women
      on tamoxifen monotherapy, the HR for recurrence in patients with reduced
      functional alleles was 1.96 (CI 1.05-3.66, P = 0.036). However, RFS analysis
      limited to four common CYP2D6 allelic variants was no longer significant (P =
      0.39). The effect of CYP2D6 genotype was increased by adjusting for adherence to
      tamoxifen therapy, but not significantly changed when adjusted for co
      administration of potent inhibitors of CYP2D6. Comprehensive genotyping of CYP2D6
      and adherence to tamoxifen therapy may be useful to identify breast cancer
      patients most likely to benefit from adjuvant tamoxifen.

PMID- 20809363
TI  - Pharmacological interventions for fertility preservation during chemotherapy.

PMID- 20809364
TI  - Association of diagnostic work-up with subsequent attendance in a breast cancer
      screening program for false-positive cases.
AB  - The objective of this study is to determine whether the likelihood of returning
      for routine breast cancer screening differed for false-positive cases depending
      on the diagnostic work-up. Using the original data from a French population-based
      breast cancer screening program, we compared the attendance rates at the
      subsequent round of screening for 16,946 and 1,127 participants who received
      negative (i.e., American College of Radiology, ACR, categories 1-2) and false
      positive mammograms, respectively. False-positive mammograms were categorized ACR
      0 (i.e., warranting additional imaging evaluation), 3 (i.e., warranting clinical
      and imaging follow-up), and 4-5 (i.e., warranting biopsy). We estimated the odds
      ratios of attendance at subsequent screening round using logistic regression,
      adjusting for age and history of previous mammography. The attendance rates at
      the subsequent screening round were 80.6% for women who received negative
      mammograms versus 69.6, 74.3, and 70.1% for women who received false-positive
      mammograms warranting additional imaging evaluation, clinical and imaging follow
      up, or biopsy, respectively. In comparison to women who received negative
      mammograms, the corresponding adjusted odds ratios of returning for routine
      screening were 0.6 [95% confidence interval (CI) 0.4-0.8], 0.8 (95% CI 0.6-0.9),
      and 0.6 (95% CI 0.4-0.8). No significant differences were found in odds ratios of
      attendance across ACR categories among women who received false-positive
      mammograms. Similar figures were observed for attending at least one of the two
      subsequent screening rounds. In conclusion, in comparison to women with normal or
      benign findings on index mammograms, false-positive cases warranting additional
      imaging evaluation, clinical and imaging follow-up, or biopsy had uniformly
      decreased odds of attending subsequent routine screening rounds.

PMID- 20809365
TI  - Mathematical modeling of evolution. Solved and open problems.
AB  - Evolution is a highly complex multilevel process and mathematical modeling of
      evolutionary phenomenon requires proper abstraction and radical reduction to
      essential features. Examples are natural selection, Mendel's laws of inheritance,
      optimization by mutation and selection, and neutral evolution. An attempt is made
      to describe the roots of evolutionary theory in mathematical terms. Evolution can
      be studied in vitro outside cells with polynucleotide molecules. Replication and
      mutation are visualized as chemical reactions that can be resolved, analyzed, and
      modeled at the molecular level, and straightforward extension eventually results
      in a theory of evolution based upon biochemical kinetics. Error propagation in
      replication commonly results in an error threshold that provides an upper bound
      for mutation rates. Appearance and sharpness of the error threshold depend on the
      fitness landscape, being the distribution of fitness values in genotype or
      sequence space. In molecular terms, fitness landscapes are the results of two
      consecutive mappings from sequences into structures and from structures into the
      (nonnegative) real numbers. Some properties of genotype-phenotype maps are
      illustrated well by means of sequence-structure relations of RNA molecules.
      Neutrality in the sense that many RNA sequences form the same (coarse grained)
      structure is one of these properties, and characteristic for such mappings.
      Evolution cannot be fully understood without considering fluctuations--each
      mutant originates form a single copy, after all. The existence of neutral sets of
      genotypes called neutral networks, in particular, necessitates stochastic
      modeling, which is introduced here by simulation of molecular evolution in a kind
      of flowreactor.

PMID- 20809366
TI  - A model-based strategy to investigate the role of microRNA regulation in cancer
      signalling networks.
AB  - In this paper we present and discuss a model-based approach to link miRNA
      translational control with cell signalling networks. MicroRNAs are small
      regulatory RNAs that are able to regulate the activity and the stability of
      specific messenger RNA and have been implicated in tumour progression due to
      their ability to translationally regulate critical oncogenes and tumour
      suppressors. In our approach, data on protein-protein interactions and miRNA
      regulation, obtained from bioinformatics databases, are integrated with
      quantitative experimental data using mathematical modelling. Predictive
      computational simulations and qualitative (bifurcation) analyses of those
      mathematical models are employed to further support the investigation of such
      multifactorial networks in the context of cancer progression. We illustrate our
      approach with the C-Myc/E2F signalling network, involved in the progression of
      several tumour subtypes, including colorectal cancer.

PMID- 20809367
TI  - A rigorous approach to investigating common assumptions about disease
      transmission: Process algebra as an emerging modelling methodology for
      epidemiology.
AB  - Changing scale, for example, the ability to move seamlessly from an individual
      based model to a population-based model, is an important problem in many fields.
      In this paper, we introduce process algebra as a novel solution to this problem
      in the context of models of infectious disease spread. Process algebra allows us
      to describe a system in terms of the stochastic behaviour of individuals, and is
      a technique from computer science. We review the use of process algebra in
      biological systems, and the variety of quantitative and qualitative analysis
      techniques available. The analysis illustrated here solves the changing scale
      problem: from the individual behaviour we can rigorously derive equations to
      describe the mean behaviour of the system at the level of the population. The
      biological problem investigated is the transmission of infection, and how this
      relates to individual interactions.

PMID- 20809370
TI  - The right comparisons in testing the minority stress hypothesis: comment on Savin
      Williams, Cohen, Joyner, and Rieger (2010).

PMID- 20809368
TI  - Identification of the hair cell soma-1 antigen, HCS-1, as otoferlin.
AB  - Hair cells, the mechanosensitive receptor cells of the inner ear, are critical
      for our senses of hearing and balance. The small number of these receptor cells
      in the inner ear has impeded the identification and characterization of proteins
      important for hair cell function. The binding specificity of monoclonal
      antibodies provides a means for identifying hair cell-specific proteins and
      isolating them for further study. We have generated a monoclonal antibody, termed
      hair cell soma-1 (HCS-1), which specifically immunolabels hair cells in at least
      five vertebrate classes, including sharks and rays, bony fish, amphibians, birds,
      and mammals. We used HCS-1 to immunoprecipitate the cognate antigen and
      identified it as otoferlin, a member of the ferlin protein family. Mutations in
      otoferlin underlie DFNB9, a recessive, nonsyndromic form of prelingual deafness
      characterized as an auditory neuropathy. Using immunocytochemistry, we find that
      otoferlin is associated with the entire basolateral membrane of the hair cells
      and with vesicular structures distributed throughout most of the hair cell
      cytoplasm. Biochemical assays indicate that otoferlin is tightly associated with
      membranes, as it is not solubilized by alterations in calcium or salt
      concentrations. HCS-1 immunolabeling does not co-localize with ribeye, a
      constituent of synaptic ribbons, suggesting that otoferlin may, in addition to
      its proposed function in synaptic vesicle release, play additional roles in hair
      cells.

PMID- 20809371
TI  - The relationship between second to fourth digit ratio, spatial cognition, and
      virtual navigation.
AB  - Studies in human and non-human animals have found that early life exposure to
      androgens may affect later spatial performance. Recent studies have suggested
      that the ratio of the second to fourth digit (2D:4D) may serve as an index of
      prenatal androgen exposure. Some studies have found that the 2D:4D ratio predicts
      adult spatial performance, although the nature of the relationship is equivocal.
      This study was designed to quantify the relationships between 2D:4D ratio,
      spatial cognition, and spatial navigation using a virtual Morris water task
      (vMWT) in a sample of young adult men and women (N = 140). The results replicated
      findings from the literature regarding sex differences in 2D:4D ratio, vMWT
      performance, and spatial cognition. However, 2D:4D ratio was not consistently
      related to spatial cognition or spatial navigation in men or women. Results were
      discussed within the framework of androgen influences on spatial cognition and
      the degree to which 2D:4D ratio serves as a marker for early life androgen
      exposure.

PMID- 20809372
TI  - Consensual sex between men and sexual violence in Australian prisons.
AB  - Estimates of the incidence of sexual coercion in men's prisons are notoriously
      variable and fraught with conceptual and methodological problems. In 2006-2007,
      we conducted a computer-assisted telephone survey of a random sample of 2,018
      male prisoners in New South Wales and Queensland. Of 2,626 eligible and available
      inmates, 76.8% consented and provided full responses. We asked about time in
      prison, sexual experience, attraction and (homo/bi/heterosexual) identity,
      attitudes, sexual contact with other inmates, reasons for having sex and
      practices engaged in, and about sexual coercion, including location and number of
      perpetrators. Most men (95.1%) identified as heterosexual. Of the total sample,
      13.5% reported sexual contact with males in their lifetime: 7.8% only outside
      prison, 2.8% both inside and outside, and 2.7% only inside prison. Later in the
      interview, 144 men (7.1% of total sample) reported sexual contact with inmates in
      prison; the majority had few partners and no anal intercourse. Most did so for
      pleasure, but some for protection, i.e., to avoid assault by someone else. Before
      incarceration, 32.9% feared sexual assault in prison; 6.9% had been sexually
      threatened in prison and 2.6% had been sexually coerced ("forced or frightened
      into doing something sexually that [they] did not want"). Some of those coerced
      reported no same-sex contact. The majority of prisoners were intolerant of male
      to-male sexual activity. The study achieved a high response rate and asked
      detailed questions to elicit reports of coercion and sex separately. Both
      consensual sex and sexual assault are less common than is generally believed.

PMID- 20809373
TI  - Use and perceptions of the internet for sexual information and partners: a study
      of young men who have sex with men.
AB  - The Internet has opened many doors with its accessibility to information,
      entertainment and web-based communities. For young men who have sex with men
      (YMSM), the Internet can provide access to information on relevant sexual
      behavior and health information, stories from other men about relationship
      issues, and a venue for locating potential sexual and dating partners.
      Understanding YMSM's motivations for going online for information, advice or
      sexual relationships, is important as the Internet becomes increasingly used not
      only as a space to find sexual partners, but also as a venue for HIV and STI
      interventions. Having an understanding of the risks associated with searching for
      partners online, and how and why YMSM use the Internet for a variety of purposes,
      can inform the development of more effective Internet-based risk reduction
      programs. This article presents qualitative and quantitative data from the
      Healthy Young Men's Study, a longitudinal study of an ethnically diverse cohort
      of 526 YMSM. Qualitative interviews (N = 24) described not only the prevalence of
      using the Internet for finding sexual partners and the possible benefits and
      risks associated with that practice, but also the processes and perceptions of
      using this mechanism. Our data indicate that YMSM used the Internet to find
      information related to sex and sexuality, seek friendships, sexual partners as
      well as "hook-ups" or casual sex. Findings were presented in relation to how YMSM
      researchers and interventionists can identify how to most effectively reach YMSM
      through online methods.

PMID- 20809374
TI  - Communicating interest in sex: verbal and nonverbal initiation of sexual activity
      in young adults' romantic dating relationships.
AB  - Relatively little is known about the day-to-day initiation of sexual activity
      between young adults in committed relationships, notably the ways in which young
      people communicate interest in sexual activity. Sexual script theory (Simon and
      Gagnon, Society 22:53-60, 1984) posits that men are traditionally the initiators
      and women the restrictors of sexual activity early in relationships. However,
      research suggests that these patterns may be different for individuals in
      committed relationships. The current study used a diary method to examine
      verbal/nonverbal and indirect/direct initiation strategies, responses to
      initiations, and patterns between initiations and responses. Participants
      included 31 men and 32 women between the ages of 18 and 24 years who were
      involved in committed heterosexual relationships. Men initiated more frequently
      than did women and most initiations were nonverbal initiation (91%) rather than
      verbal (65%). Responses to initiations tended to match the initiators' choice of
      strategies, suggesting that synchrony plays an important role in initiation
      patterns. The findings have implications for understanding sexual communication
      as well as relationship and sexual satisfaction among young adults.

PMID- 20809375
TI  - Young adults' emotional reactions after hooking up encounters.
AB  - Hooking up, or a sexual encounter ranging from kissing to intercourse that occurs
      on one occasion and where the partners do not necessarily expect future physical
      encounters or a committed relationship, has become commonplace among college
      students. This study (N = 500) examined gender differences in emotional reactions
      after hooking up and explored the relationship between specific processes in the
      hooking up encounter and reactions to hooking up. Compared to women, men reported
      more positive and fewer negative emotional reactions; however, both men and women
      reported that the experience was largely more positive than negative. Coital hook
      ups were associated with fewer negative emotional responses for men as compared
      to women who engaged in coital and non-coital hook ups and to men who engaged in
      non-coital hook ups. For those who engaged in coital hook ups, women reported
      that condom use was associated with fewer positive and more negative emotional
      reactions whereas condom use was related to fewer negative emotion reactions for
      men. Negative emotional reactions were also related to reports of depressive
      symptoms and feelings of loneliness; however, feelings of loneliness were not
      related to negative emotional reactions after accounting for young adults'
      positive emotional reactions. Positive emotional reactions were related to hope
      for and discussion of a committed relationship. Implications for relationship
      education and future research are outlined.

PMID- 20809376
TI  - Brief report: Prevalence of autistic spectrum disorders in the Sultanate of Oman.
AB  - Prevalence of autistic spectrum disorders (ASD) in Oman is unknown. We conducted
      a cross-sectional study to estimate the prevalence of ASD among 0-14 year old
      children. Diagnoses were made as per DSM-IV-TR criteria and supplemented with
      information collected with the standard Childhood Autism Rating Scale (CARS)
      questionnaire. A total 113 cases of ASD were enumerated nationwide, indicating an
      overall prevalence of 1.4 (95% CI 1.2, 1.7) cases per 10,000 children aged 0-14
      years. More prevalent cases were among boys (75%) and among low-income families.
      Ritualistic interests were more common among girls as an onset-symptom compared
      to boys (p = 0.03). The reported low prevalence of ASD in Oman is likely due to
      under-diagnosis and under-reporting.

PMID- 20809378
TI  - Abdominoplasty combined with Cesarean delivery: evaluation of the practice.
AB  - Abdominoplasty is an aesthetic surgical procedure that restores abdominal
      contouring. Repeated pregnancy usually leads to lower abdominal skin redundancy
      and excess fat accumulation. Delivery via Cesarean section adds weakness to the
      lower abdominal wall muscles and yields a lower transverse Cesarean scar.
      Recently and in some cultures, abdominoplasty is requested at the same time of
      Cesarean delivery. Those women usually want to get the benefit of undergoing the
      abdominoplasty combined with Cesarean delivery in the same setting, thus avoiding
      a future surgery. This study was designed to evaluate the aesthetic outcome of
      combined abdominoplasty with Cesarean delivery. The study included 50 pregnant
      women from February 2008 to December 2009 with an average follow up period of 6
      months. Nine patients (18%) developed wound infection; three of them (9%)
      developed wound dehiscence. Six patients (12%) developed lower abdominal skin
      necrosis; three of them (6%) were treated conservatively and healed by secondary
      intention, while surgical debridement and secondary sutures were needed in the
      other three patients (6%). Residual abdominal skin redundancy in 9 patients
      (18%), outward bulging of the abdomen and lack of waist definition in 16 patients
      (32%), and outward bulging of the umbilicus in 12 patients (24%) were the
      reported unaesthetic results. The results were compared with results of 80
      abdominoplasties in nonpregnant women. The study concluded that abdominoplasty
      combined with Cesarean delivery carries a higher incidence of complications and
      does not give the desired aesthetic outcome. The authors do not recommend this
      practice.

PMID- 20809377
TI  - Social and non-social cueing of visuospatial attention in autism and typical
      development.
AB  - Three experiments explored attention to eye gaze, which is incompletely
      understood in typical development and is hypothesized to be disrupted in autism.
      Experiment 1 (n = 26 typical adults) involved covert orienting to box, arrow, and
      gaze cues at two probabilities and cue-target times to test whether reorienting
      for gaze is endogenous, exogenous, or unique; experiment 2 (total n = 80: male
      and female children and adults) studied age and sex effects on gaze cueing. Gaze
      cueing appears endogenous and may strengthen in typical development. Experiment 3
      tested exogenous, endogenous, and gaze-based orienting in 25 typical and 27
      Autistic Spectrum Disorder (ASD) children. ASD children made more saccades,
      slowing their reaction times; however, exogenous and endogenous orienting,
      including gaze cueing, appear intact in ASD.

PMID- 20809379
TI  - [The crooked nose: correction of dorsal and caudal septal deviations].
AB  - The deviated nose represents a complex cosmetic and functional problem. Septal
      surgery plays a central role in the successful management of the externally
      deviated nose. This study included 800 patients seeking rhinoplasty to correct
      external nasal deviations; 71% of these suffered from variable degrees of nasal
      obstruction. Septal surgery was necessary in 736 (92%) patients, not only to
      improve breathing, but also to achieve a straight, symmetric external nose. A
      graduated surgical approach was adopted to allow correction of the dorsal and
      caudal deviations of the nasal septum without weakening its structural support to
      the nasal dorsum or nasal tip. The approach depended on full mobilization of
      deviated cartilage, followed by straightening of the cartilage and its fixation
      in the corrected position by using bony splinting grafts through an external
      rhinoplasty approach.

PMID- 20809380
TI  - Real-time adherence monitoring for HIV antiretroviral therapy.
AB  - Current adherence assessments typically detect missed doses long after they
      occur. Real-time, wireless monitoring strategies for antiretroviral therapy may
      provide novel opportunities to proactively prevent virologic rebound and
      treatment failure. Wisepill, a wireless pill container that transmits a cellular
      signal when opened, was pilot tested in ten Ugandan individuals for 6 months.
      Adherence levels measured by Wisepill, unannounced pill counts, and self-report
      were compared with each other, prior standard electronic monitoring, and HIV RNA.
      Wisepill data was initially limited by battery life and signal transmission
      interruptions. Following device improvements, continuous data was achieved with
      median (interquartile range) adherence levels of 93% (87-97%) by Wisepill, 100%
      (99-100%) by unannounced pill count, 100% (100-100%) by self-report, and 92% (79
      98%) by prior standard electronic monitoring. Four individuals developed
      transient, low-level viremia. After overcoming technical challenges, real-time
      adherence monitoring is feasible for resource-limited settings and may detect
      suboptimal adherence prior to viral rebound.

PMID- 20809381
TI  - Screening for gestational diabetes mellitus: cost-utility of different screening
      strategies based on a woman's individual risk of disease.
AB  - AIMS/HYPOTHESIS: The cost-effectiveness of eight strategies for screening for
      gestational diabetes (including no screening) was estimated with respect to the
      level of individual patient risk. METHODS: Cost-utility analysis using a decision
      analytic model populated with efficacy evidence pooled from recent randomised
      controlled trials, from the funding perspective of the National Health Service in
      England and Wales. Seven screening strategies using various combinations of
      screening and diagnostic tests were tested in addition to no screening. The
      primary outcome measure was the incremental cost per quality-adjusted life-year
      (QALY) over a lifetime. RESULTS: The strategy that has the greatest likelihood of
      being cost-effective is dependent on the risk of gestational diabetes mellitus
      for each individual woman. When gestational diabetes mellitus risk is <1% then
      the no screening/treatment strategy is cost-effective; where risk is between 1.0%
      and 4.2% fasting plasma glucose followed by OGTT is most likely to be cost
      effective; and where risk is >4.2%, universal OGTT is most likely to be cost
      effective. However, acceptability of the test alters the most cost-effective
      strategy. CONCLUSIONS/INTERPRETATION: Screening for gestational diabetes can be
      cost-effective. The best strategy is dependent on the underlying risk of each
      individual and the acceptability of the tests used. The current study suggests
      that if a woman's individual risk of gestational diabetes could be accurately
      predicted, then healthcare resource allocation could be improved by providing an
      individualised screening strategy.

PMID- 20809382
TI  - Gene-expression profiling in breast cancer: bespoke cancer therapy or more
      fiction than science?

PMID- 20809383
TI  - Sexual activity of HIV patients.

PMID- 20809384
TI  - Use of Gamma locking nail((r)) in tri-planar osteotomy in bilateral severe
      slipped upper femoral epiphysis: a case study and literature review.
AB  - INTRODUCTION: Slipped upper femoral epiphysis (SUFE) is a common condition
      affecting adolescent boys and girls. It is classified as acute, chronic or acute
      on chronic. The slip can be mild, moderate or severe. MATERIALS AND METHODS: We
      present a case of chronic severe SUFE in a 16-year-old male with significant
      fixed bilateral deformities requiring osteotomy of proximal femur and
      stabilisation with short locking Gamma nail((r)). To our knowledge, this device
      has not been used in stabilisation of osteotomies in chronic SUFE. CONCLUSION:
      The purpose of this paper is to describe the results of our fixation method and
      also to increase the awareness in orthopaedic surgeon about the usefulness of
      Gamma locking nail((r)) in these difficult situations.

PMID- 20809385
TI  - Threatened and less known ethnomedicinal plants of an Indo-Burma hotspot region:
      conservation implications.
AB  - Present paper provides first-hand information of certain ethnomedicinal plants
      from an Indo-Burma hotspot region (Mizoram, NE India). Forty ethnomedicinal
      plants recorded for the first time from this site of particular ecological
      relevance. Medical applications and conservation status of recorded plants have
      been described. In light of the fact that biodiversity characterization is now
      increasingly being recognized as an endangered field, such sort of biodiversity
      inventorying, monitoring, and assessment works are relevant particularly in
      relation to plants which are intimately linked with human welfare. Moreover,
      sustainable use of such components of biodiversity may extend important ecosystem
      services and also assist in their conservation.

PMID- 20809386
TI  - Stochastic landslide vulnerability modeling in space and time in a part of the
      northern Himalayas, India.
AB  - Little is known about the quantitative vulnerability analysis to landslides as
      not many attempts have been made to assess it comprehensively. This study
      assesses the spatio-temporal vulnerability of elements at risk to landslides in a
      stochastic framework. The study includes buildings, persons inside buildings, and
      traffic as elements at risk to landslides. Building vulnerability is the expected
      damage and depends on the position of a building with respect to the landslide
      hazard at a given time. Population and vehicle vulnerability are the expected
      death toll in a building and vehicle damage in space and time respectively. The
      study was carried out in a road corridor in the Indian Himalayas that is highly
      susceptible to landslides. Results showed that 26% of the buildings fall in the
      high and very high vulnerability categories. Population vulnerability inside
      buildings showed a value >0.75 during 0800 to 1000 hours and 1600 to 1800 hours
      in more buildings that other times of the day. It was also observed in the study
      region that the vulnerability of vehicle is above 0.6 in half of the road
      stretches during 0800 hours to 1000 hours and 1600 to 1800 hours due to high
      traffic density on the road section. From this study, we conclude that the
      vulnerability of an element at risk to landslide is a space and time event, and
      can be quantified using stochastic modeling. Therefore, the stochastic
      vulnerability modeling forms the basis for a quantitative landslide risk analysis
      and assessment.

PMID- 20809387
TI  - Estimation of nested spatial patterns and seasonal variation in the longitudinal
      distribution of Sicyopterus japonicus in the Datuan Stream, Taiwan by using
      geostatistical methods.
AB  - This study attempts to determine the scale-dependent hierarchical spatial
      variation and longitudinal distributions of Sicyopterus japonicus year round. The
      distribution of S. japonicus in the Datuan Stream in northern Taiwan was surveyed
      during the fall and winter 2007, as well as the spring and summer of 2008. The
      spatial structure of S. japonicus density was modeled using geostatistics. The
      longitudinal distributions of S. japonicus density were then estimated using
      kriging and hydrology distance with nested variogram models. Variography results
      indicate that nested variogram models could reflect the hierarchical structure in
      the spatial variation of seasonal S. japonicus density, with the small, median,
      and large ranges representing three nested scales. Models for the four seasons
      were consistent in that they shared the same shape of variogram models with
      various ranges and sill values. This model shape consistency implies stationary
      spatial correlations in the longitudinal fish distribution across the four
      seasons. The Kriging geostatistical method based on the multiple scales nested
      variogram models also provided robust estimates of S. japonicus densities at
      unsampled sections. We conclude that S. japonicus densities exhibit hierarchical
      patterns and variation in the four seasons along the study stream. Geostatistical
      methods with a nested variograms and hydrological distance are a highly effective
      means of delineating the hierarchical structure in longitudinal patterns of S.
      japonicus density in each season, providing estimates of the S. japonicus density
      for hierarchically structured spatial distributions and expanding knowledge of S.
      japonicus beyond the limits imposed by spatial and temporal scales.

PMID- 20809388
TI  - Total suspended matter observation in the Pearl River estuary from in situ and
      MERIS data.
AB  - Based on the cruise data collected in the Pearl River estuary (PRE) in May 2008,
      an empirical two-band model by using the ratio of R (rs) at 629 and 671 nm was
      established to retrieve total suspended matter (TSM) concentration with the
      determination coefficient (R(2)) of 0.854, mean relative error (MRE) of 7.483%,
      and root-mean-square error (RMSE) of 1.295 mg L( - 1). To match with medium
      resolution imaging spectrometer (MERIS) bands, in situ remote sensing reflectance
      was re-sampled to the bandwidth of 10 nm. The relationship between TSM and re
      sampled R (rs) at 620 nm (MERIS band 6) and 665 nm (MERIS band 7) are obtained
      (R(2) = 0.748, RMSE = 1.697 mg L( - 1), MRE = 8.785%, n = 13). Additionally, to
      map the spatial distribution of TSM in the PRE, MERIS level_1B data were
      calibrated using a multiple linear regression model based on in situ R (rs).
      Another dataset collected in the PRE in January 2004 was used to validate the two
      band model and also applied to map TSM distribution from MERIS image. The
      comparison between measured TSM values and modeled ones showed satisfactory
      results (R(2) = 0.753, MRE = 22.199%, and RMSE = 2.603 mg L( - 1)).

PMID- 20809389
TI  - A novel environmental indicator for monitoring of pesticides.
AB  - The identification of an indicator for monitoring pesticides is a very effective
      analytical approach because it allows one to schedule and simplify the analytical
      routine. In this study, a new indicator has been designed, which has to be able
      to define a scale of priorities in the pesticides monitoring. A starting equation
      was developed involving the escaping tendency of a given substance from a phase
      (based on the Mackay model I level). The reliability of the indicator was tested
      by application to a model system, consisting of a defined and limited area,
      choosing water as matrix over a period of 6 years. A group of marker compounds
      was also defined to implement the predictive efficacy of the indicator. The
      results obtained by modeling were compared to those obtained by experimentation
      of the same model system. The indicator was subsequently and appropriately
      modified creating a new equation, including a kinetic factor, which considers the
      environmental degradation processes. The effect of the rectified indicator was
      consistent with the sales data list of compounds, when applied to the markers.
      The indicator developed in this study, tested as a model on specific area-phase
      period (Province of Siena, water phase, 2000-2006), is applicable to any other
      area-phase-period, adjusting the partition value of the Mackay model for the case
      under study.

PMID- 20809390
TI  - Heart rate reduction in cardiovascular disease and therapy.
AB  - Heart rate influences myocardial oxygen demand, coronary blood flow, and
      myocardial function. Clinical and experimental studies support an association
      between elevated resting heart rate and a broad range of maladaptive effects on
      the function and structure of the cardiovascular system. Heart rate has been
      shown to be an important predictor of mortality in cardiovascular disorders such
      as coronary artery disease, myocardial infarction, and chronic heart failure.
      This review summarizes the specific influence of heart rate on vascular
      morphology and function as well as on myocardial lesions leading from early
      impact on vascular homeostasis to myocardial hemodynamics in chronic heart
      failure. Heart rate can be easily determined during physical examination of the
      patient and therefore allows a simple hint on prognosis and efficiency of
      therapy.

PMID- 20809391
TI  - Synthetic triterpenoid CDDO derivatives modulate cytoprotective or immunological
      properties in astrocytes, neurons, and microglia.
AB  - 2-Cyano-3,12-dioxoolean-1, 9-dien-28-oic acid (CDDO) is a semisynthetic
      triterpenoid. CDDO derivatives with an amide, butyl ester (BE), imidazolide (IM),
      or trifluoroethyl amide (TFEA) group at position C-28 of CDDO were evaluated in
      glial and neuronal cells, in vitro. Changes in intracellular NADPH:quinone
      oxidoreductase (NQO1) levels, protection against oxidative toxicity, endotoxin
      induced free-radical production, and the median lethal concentration (LC50) were
      assessed. All four CDDO derivatives at nanomolar concentrations increased NQO1
      levels in astrocytes and moderately in neurons, but not in microglial cells.
      Pretreatment with 100 nM of CDDO-amide, CDDO-TFEA, or CDDO-IM protected
      astrocytes from hydrogen peroxide toxicity. Only CDDO-amide protected neuronal
      cells. Pretreatment of microglial cells with CDDO derivatives at nanomolar
      concentrations attenuated endotoxin-induced nitric oxide protection. The
      effectiveness for NQO1 induction, protection against oxidative toxicity, and
      attenuation of nitric oxide production, as well as cell viability at higher
      concentrations, varied among the derivatives with different functional groups at
      C-28. CDDO-amide had comparable or even a greater effectiveness at altering
      cytoprotective and immunomodulatory properties while having higher LC50 values
      for each neural cell type examined. These results indicate that derivatives of
      CDDO modulate important pathways relevant to many neurological diseases that
      involve both chronic inflammation and free-radical damage with variable effects
      based on the functional group at C-28 and cell type.

PMID- 20809392
TI  - Assessment of the 3-D shape and mechanics of the proximal femur using a shape
      template and a bone mineral density image.
AB  - Measurement of bone mineral density (BMD) by DXA (dual-energy X-ray
      absorptiometry) is generally considered to be the clinical golden standard
      technique to diagnose osteoporosis. However, BMD alone is only a moderate
      predictor of fracture risk. Finite element analyses of bone mechanics can
      contribute to a more accurate prediction of fracture risk. In this study, we
      applied a method to estimate the 3D geometrical shape of bone based on a 2D BMD
      image and a femur shape template. Proximal femurs of eighteen human cadavers were
      imaged with computed tomography (CT) and divided into two groups. Image data from
      the first group (N = 9) were applied to create a shape template by using the
      general Procrustes analysis and thin plate splines. This template was then
      applied to estimate the shape of the femurs in the second group (N = 9), using
      the 2D BMD image projected from the CT image, and the geometrical errors of the
      shape estimation method were evaluated. Finally, finite element analysis with
      stance loading condition was conducted based on the original CT and the estimated
      geometrical shape to evaluate the effect of the geometrical errors on the outcome
      of the simulations. The volumetric errors induced by the shape estimation method
      itself were low (<0.6%). Increasing the number of bone specimens used for the
      template decreased the geometrical errors. When nine bones were used for the
      template, the mean distance difference (+/-SD) between the estimated and the CT
      shape surfaces was 1.2 +/- 0.3 mm, indicating that the method was feasible for
      estimating the shape of the proximal femur. Small errors in geometry led
      systematically to larger errors in the mechanical simulations. The method could
      provide more information of the mechanical characteristics of bone based on 2D
      BMD radiography and could ultimately lead to more sensitive diagnosis of
      osteoporosis.

PMID- 20809393
TI  - Adjuvant stereotactic body radiotherapy for resected pancreatic adenocarcinoma
      with close or positive margins.
AB  - PURPOSE: The aim of this study was to evaluate the role of stereotactic body
      radiotherapy (SBRT) as adjuvant therapy for resected pancreatic adenocarcinoma
      with close or positive margins. METHODS: Between September 2006 and January 2010,
      24 patients were treated with adjuvant SBRT following surgical resection. Eight
      (33.3%) patients had close margins of 1-2.5 mm to the retroperitoneal, vascular
      structures, and periduodenal adipose tissue. Sixteen (66.7%) patients had
      positive margins at retroperitoneal margin and vascular structures. Twenty-three
      patients received 24 Gy (20-24 Gy) in one fraction, and one had 30 Gy in three
      fractions. The median target volume was 11 cc (4.5-30 cc). Eighteen patients were
      treated with the Cyberknife(r) Robotic Radiosurgery System and six patients were
      treated with TrilogyTM intensity-modulated radiosurgery. Kaplan-Meier survival
      analyses were used to estimate freedom-from-local-progression (FFLP), and overall
      survival (OS) rates. PET/CT or CT was used to monitor disease recurrence
      following SBRT. RESULTS: The median follow-up for all patients was 12.5 months
      (1.4-39.5 months), and among surviving patients it was 16.3 months (2-39.5
      months). The FFLP rates at 6 months, 1 and 2 years were 94.7%, 66%, and 44%,
      respectively. Overall, FFLP was achieved in seven (87.5%) patients with close
      margins, and 10 (62.5%) with positive margins. After SBRT, 19 patients resumed or
      started a 6-month course of gemcitabine-based chemotherapy at a median interval
      of 18 days (range, 9-31 days) post-SBRT. The median OS was 26.7 months and the 1-
      and 2-year OS rates were 80.4% and 57.2%, respectively. Of the 24 patients, 12
      (50%) developed distant metastases of whom two (25%) had close margins and 10
      (62.5%) had positive margins. Ten patients (41.7%) were free of progression at
      last follow-up (range, 3-39.5 months). Three patients (12.5%) had grade 1-2 acute
      GI toxicities, and two patients (8.3%) had grade 1 and 2 late toxicities. No
      patients experienced grade 3 or 4 toxicity, including bowel perforation,
      secondary to SBRT. CONCLUSIONS: Our data suggest that adjuvant SBRT for resected
      pancreatic cancer can be achieved with minimal toxicity. This shorter treatment
      course allowed initiation of systemic chemotherapy shortly after the completion
      of SBRT.

PMID- 20809394
TI  - Primary diffuse large B-cell lymphoma of ampulla of vater: a rare case report.
AB  - INTRODUCTION: Primary lymphomas of the ampulla of Vater are extremely rare. Among
      these most frequent are follicular lymphomas followed by mucosa-associated
      lymphoid tissue-type lymphoma. CASE REPORT: We report a case of a 36-year-old
      female diagnosed with diffuse large B-cell lymphoma (DLBCL) of the ampulla of
      Vater. Endoscopic biopsy was non-diagnostic. Whipple's resection was performed.
      The patient was given six cycles of chemotherapy. One year later, the patient
      developed recurrence at the anastomotic site and again treated with combination
      chemotherapy. Patient is doing well after 2 years of initial surgery. DISCUSSION:
      Tumors of the ampulla of Vater are included in the pancreaticobiliary group of
      neoplasms; in some instances, it is almost impossible to ascertain the exact
      origin of the tumor anatomically. The patients of primary lymphoma of the ampulla
      of Vater may have a varied clinical presentation or may be completely
      asymptomatic and detected during routine medical check-ups for gastric cancer
      screening. CONCLUSION: We present a rare case of primary DLBCL of the
      periampullary region. Due to the rarity of these lesions, their ability to
      masquerade as periampullary carcinomas, and the fact that these tumors show a
      good response to chemotherapy, an early diagnosis is desirable.

PMID- 20809395
TI  - Budd-Chiari syndrome in pleural mesothelioma.

PMID- 20809396
TI  - Comparison of cancer care for hepatocellular carcinoma at two tertiary-care
      referral centers from high and low endemic regions for viral hepatitis.
AB  - BACKGROUND: Risk factors for hepatocellular carcinoma (HCC) have geographic
      variability but differences in care have not been described. We reviewed the
      presentation, management, and outcomes of HCC patients from two tertiary-referral
      centers in Central Saudi Arabia and Atlantic Canada during 1997-2002. METHODS:
      Data were extracted from health records of 96 Saudi and 80 Canadian consecutive
      patients with HCC. RESULTS: Mean age (+/- SEM) of the two groups were similar (64
      + 1 and 65 + 1 years) with 93% versus 75% males amongst Canadian and Saudi
      patients, respectively. In Canada, underlying disease was alcohol-related
      cirrhosis (45%), cryptogenic cirrhosis (26%), or hepatitis C (13%). For Saudis,
      HCC cases were attributed to hepatitis C (47%), cryptogenic cirrhosis (27%), and
      hepatitis B (21%). At initial presentation, Saudi patients had more vascular
      invasion and distant metastases while Canadians had more advanced liver disease.
      The tumor-specific prognostic classifications were comparable. Due to center
      specific expertise or preference, symptomatic treatment was more common amongst
      Saudi patients (83% versus 42%) while more Canadians underwent local palliative
      interventions (52% versus 12%). Frequency of potentially curative therapies
      including resection and transplantation were similar at both centers. There was
      no difference in overall median survival (14 versus 10 months) amongst Canadian
      and Saudi patients. CONCLUSIONS: This study validates divergence in HCC
      presentation between low and high endemic regions for viral hepatitis. In
      addition, for the first time, differences in cancer care of HCC are documented.

PMID- 20809397
TI  - High rates of advanced gastric cancer in community of Flushing, New York.
AB  - BACKGROUND: Gastric cancer remains a major public health issue and is a leading
      cause of death worldwide, accounting for 600,000 deaths annually. Over the last
      decades, there has been a steady decline in the incidence rates of gastric
      cancer. Furthermore, the incidence rates of gastric cancer in different parts of
      the country vary due to epidemiological and migration trends. Despite these
      trends, several studies that have continued to observe high rates of gastric
      cancer in populations that come from high-risk regions. AIM OF THE STUDY: The aim
      of the study was to describe the gastric cancer patients presenting NYHQ with an
      emphasis on those presenting at a young age and advanced disease. A subanalysis
      of the Asian population was also done, which is considered a high-risk group.
      METHODS: Consecutive chart review of patients admitted with gastric cancer from
      January 2000 to August 2008 was extracted from the Oncology registry at NYHQ.
      Parameters that were evaluated were age, sex, race, type of gastric cancer, and
      stage of gastric cancer at initial presentation. The SAS/PC software package (SAS
      Institute Inc., Cary, NC) was employed for statistical analyses. RESULTS: Four
      hundred fifty-seven patients were diagnosed with gastric cancer. Approximately
      one third of the total patients were younger than 60 years of age. Of the Asian
      patients, almost half the patients (48.8%) had advanced disease of which two
      thirds were under the age of 60 years. CONCLUSION: The rates of advanced gastric
      cancer observed at NYHQ are significant and comparable to recent epidemiology
      literature on rates in Asian populations in Asia. Communities, like Flushing, NY,
      may benefit from early detection of gastric cancers, similar to those instituted
      in Japan and Taiwan.

PMID- 20809398
TI  - Neurosurgical craniotomy localization using a virtual reality planning system
      versus intraoperative image-guided navigation.
AB  - PURPOSE: Accurate craniotomy placement is essential for frameless neuronavigation
      in minimally invasive neurosurgery. A craniotomy using virtual reality (VR) can
      be as accurate as neuronavigation. METHODS: We prospectively enrolled 48 patients
      that underwent minimally invasive cranial procedures planned using VR, followed
      by neuronavigation. First, craniotomies were planned using VR derived
      measurements. Second, frameless neuronavigation was applied to define the
      craniotomy. The locations of these paired craniotomies were compared. A correctly
      placed craniotomy was defined as one that enabled the surgeon to totally remove
      the pathology without need to enlarge the craniotomy intraoperatively. RESULTS:
      Using VR, the size and the position of the craniotomy were measured correctly in
      47 of 48 cases (98%). In 44 of 48 cases (92%), neuronavigation identified the
      craniotomy site correctly. In cases where neuronavigation failed, minimally
      invasive surgery was successfully completed using preoperative VR surgery
      planning. No statistically significant difference was found between craniotomy
      localization using VR surgery planning or standard frameless neuronavigation (p =
      0.36). CONCLUSION: The craniotomy for minimally invasive neurosurgical procedures
      can be identified accurately using VR surgery planning or neuronavigation. In
      cases of neuronavigation failure, VR surgery planning serves as an effective
      backup system to perform a minimally invasive operation.

PMID- 20809399
TI  - Nitric oxide release follows endothelial nanomechanics and not vice versa.
AB  - In the vascular endothelium, mechanical cell stiffness (K) and nitric oxide (NO)
      release are tightly coupled. "Soft" cells release more NO compared to "stiff"
      cells. Currently, however, it is not known whether NO itself is the primary
      factor that softens the cells or whether NO release is the result of cell
      softening. To address this question, a hybrid fluorescence/atomic force
      microscope was used in order to measure changes in K and NO release
      simultaneously in living vascular endothelial cells. Aldosterone was applied to
      soften the cells transiently and to trigger NO release. NO synthesis was then
      either blocked or stimulated and, simultaneously, K was measured. Cell
      indentation experiments were performed to evaluate K, while NO release was
      measured either by an intracellular NO-dependent fluorescence indicator (DAF
      FM/DA) or by NO-selective electrodes located close to the cell surface. After the
      application of aldosterone, K decreases, within 10 min, to 80.5 +/- 1.7% of
      control (100%). DAF-FM fluorescence intensity increases simultaneously to 132.9
      +/- 2.2%, which indicates a significant increase in the activity of endothelial
      NO synthase (eNOS). Inhibition of eNOS (by N (omega)-nitro-L: -arginine methyl
      ester) blocks the NO release, but does not affect the aldosterone-induced changes
      in K. Application of an eNOS-independent NO donor (NONOate/AM) raises
      intracellular NO concentration, but, again, does not affect K. Data analysis
      indicates that a decrease of K by about 10% is sufficient to induce a significant
      increase of eNOS activity. In conclusion, these nanomechanic properties of
      endothelial cells in vascular endothelium determine NO release, and not vice
      versa.

PMID- 20809400
TI  - Biomarkers in Parkinson's disease.
AB  - Biomarkers are objectively measured characteristics that are indicators of normal
      biological processes, pathogenic processes, or responses to therapeutic
      interventions. To date, clinical assessment remains the gold standard in the
      diagnosis of Parkinson's disease (PD) and clinical rating scales are well
      established as the gold standard for tracking progression of PD. Researchers have
      identified numerous potential biomarkers that may aid in the differential
      diagnosis of PD and/or tracking disease progression. Clinical, genetic, blood and
      cerebrospinal fluid (proteomics, transcriptomics, metabolomics), and neuroimaging
      biomarkers may provide useful tools in the diagnosis of PD and in measuring
      disease progression and response to therapies. Some potential biomarkers are
      inexpensive and do not require much technical expertise, whereas others are
      expensive or require specialized equipment and technical skills. Many potential
      biomarkers in PD show great promise; however, they need to be assessed for their
      sensitivity and specificity over time in large and varied samples of patients
      with and without PD.

PMID- 20809401
TI  - The new classification of primary progressive aphasia into semantic, logopenic,
      or nonfluent/agrammatic variants.
AB  - Primary progressive aphasia (PPA), typically resulting from a neurodegenerative
      disease such as frontotemporal lobar degeneration or Alzheimer's disease, is
      characterized by a progressive loss of specific language functions with relative
      sparing of other cognitive domains. Three variants of PPA are now recognized:
      semantic variant, logopenic variant, and nonfluent/agrammatic variant. We discuss
      recent work characterizing the neurolinguistic, neuropsychological, imaging and
      pathologic profiles associated with these variants. Improved reliability of
      diagnoses will be increasingly important as trials for etiology-specific
      treatments become available. We also discuss the implications of these syndromes
      for theories of language function.

PMID- 20809402
TI  - [The ENETS and UICC TNM classification of neuroendocrine tumors of the
      gastrointestinal tract and the pancreas: comment].

PMID- 20809404
TI  - [New TNM classification of malignant lung tumours].
AB  - The staging system for lung tumours is now recommended for the classification of
      both non-small-cell and small-cell lung cancer as well as for carcinoid tumours
      of the lung. The T classifications have been redefined: T1 has been subclassified
      as T1a (<= 2 cm in size) and T1b (> 2-3 cm in size). T2 has been subclassified as
      T2a (> 3-5 cm in size) and T2b (> 5-7 cm in size). T2 (> 7 cm in size) has been
      reclassified as T3. Multiple tumour nodules in the same lobe have been
      reclassified from T4 to T3. Multiple tumour nodules in the same lung but a
      different lobe have been reclassified from M1 to T4. No changes have been made in
      the N classification. The M classification has been redefined: M1 has been
      subdivided into M1a and M1b. Malignant pleural and pericardial effusions have
      been reclassified from T4 to M1a. Separate tumour nodules in the contralateral
      lung have been reclassified from T4 to M1a. M1b designates distant metastasis.

PMID- 20809405
TI  - [Changes in the TNM classification of head and neck tumors].
AB  - Only minor modifications were introduced in the classification of squamous cell
      carcinomas of the oro- and hypopharynx, namely in the definition of some T and N
      categories. A new TNM classification has been introduced for mucosal melanoma of
      the head and neck. Some proposals for ramification of the T1 categories of
      thyroid tumours have been adopted from the TNM Supplement, unfortunately not
      those proposed for the T3 categories. The new TNM classification of Merkel cell
      carcinomas, which frequently occur in the head and neck region, is also
      discussed.

PMID- 20809406
TI  - Competitive interactions between native and invasive exotic plant species are
      altered under elevated carbon dioxide.
AB  - We hypothesized that the greater competitive ability of invasive exotic plants
      relative to native plants would increase under elevated CO(2) because they
      typically have traits that confer the ability for fast growth when resources are
      not limiting and thus are likely to be more responsive to elevated CO(2). A
      series of competition experiments under ambient and elevated CO(2) glasshouse
      conditions were conducted to determine an index of relative competition intensity
      for 14 native-invasive exotic species-pairs. Traits including specific leaf area,
      leaf mass ratio, leaf area ratio, relative growth rate, net assimilation rate and
      root weight ratio were measured. Competitive rankings within species-pairs were
      not affected by CO(2) concentration: invasive exotic species were more
      competitive in 9 of the 14 species-pairs and native species were more competitive
      in the remaining 5 species-pairs, regardless of CO(2) concentration. However,
      there was a significant interaction between plant type and CO(2) treatment due to
      reduced competitive response of native species under elevated compared with
      ambient CO(2) conditions. Native species had significantly lower specific leaf
      area and leaf area ratio under elevated compared with ambient CO(2). We also
      compared traits of more-competitive with less-competitive species, regardless of
      plant type, under both CO(2) treatments. More-competitive species had smaller
      leaf weight ratio and leaf area ratio, and larger relative growth rate and net
      assimilation rate under both ambient and elevated CO(2) conditions. These results
      suggest that growth and allocation traits can be useful predictors of the outcome
      of competitive interactions under both ambient and elevated CO(2) conditions.
      Under predicted future atmospheric CO(2) conditions, competitive rankings among
      species may not change substantially, but the relative success of invasive exotic
      species may be increased. Thus, under future atmospheric CO(2) conditions, the
      ecological and economic impact of some invasive exotic plants may be even greater
      than under current conditions.

PMID- 20809407
TI  - Nitrogen deposition limits photosynthetic response to elevated CO2 differentially
      in a dioecious species.
AB  - Sexual dimorphisms of dioecious plants are important in controlling and
      maintaining sex ratios under changing climate environments. Yet, little is known
      about sex-specific responses to elevated CO(2) with soil nitrogen (N) deposition.
      To investigate sex-related physiological and biochemical responses to elevated
      CO(2) with N deposition, Populus cathayana Rehd. was employed as a model species.
      The cuttings were subjected to two CO(2) regimes (350 and 700 MUmol mol(-1)) with
      two N levels (0 and 5 g N m(-2) year(-1)). Our results showed that elevated CO(2)
      and N deposition separately increased the total number of leaves, leaf area (LA),
      leaf mass, net photosynthetic rate (P(n)), light saturated photosynthetic rate
      (P(max)), chlorophyll a (Chl a), and chlorophyll a to chlorophyll b ratio (Chl
      a/b) in both males and females of P. cathayana. However, the effects on LA, leaf
      mass, P(n), P(max), Chl a and Chl a/b were weakened under the combined treatment
      of elevated CO(2) and N deposition. Males had higher leaf mass, P(n), P(max),
      apparent quantum yield (Phi), carboxylation efficiency (CE), Chl a, Chl a/b, leaf
      N, and root carbon to N ratio (C/N) than did females under elevated CO(2) with N
      deposition. In contrast to males, females had significantly higher levels of
      soluble sugars in leaves and greater starch accumulation in roots and stems under
      the same condition. The results of the present work imply that P. cathayana
      females are more responsive and suffer from greater negative effects on growth
      and photosynthetic capacity than do males when grown under elevated CO(2) with
      soil N deposition.

PMID- 20809408
TI  - Inter- and under-canopy soil water, leaf-level and whole-plant gas exchange
      dynamics of a semi-arid perennial C4 grass.
AB  - It is not clear if tree canopies in savanna ecosystems exert positive or negative
      effects on soil moisture, and how these might affect understory plant carbon
      balance. To address this, we quantified rooting-zone volumetric soil moisture
      (theta(25 cm)), plant size, leaf-level and whole-plant gas exchange of the
      bunchgrass, bush muhly (Muhlenbergia porteri), growing under and between mesquite
      (Prosopis velutina) in a southwestern US savanna. Across two contrasting monsoon
      seasons, bare soil theta(25 cm) was 1.0-2.5% lower in understory than in the
      intercanopy, and was consistently higher than in soils under grasses, where
      theta(25 cm) was similar between locations. Understory plants had smaller canopy
      areas and volumes with larger basal diameters than intercanopy plants. During an
      above-average monsoon, intercanopy and understory plants had similar seasonal
      light-saturated leaf-level photosynthesis (A(net-sat)), stomatal conductance (g(s
      sat)), and whole-plant aboveground respiration (R(auto)), but with higher whole
      plant photosynthesis (GEP(plant)) and transpiration (T(plant)) in intercanopy
      plants. During a below-average monsoon, intercanopy plants had higher diurnally
      integrated GEP(plant), R(auto), and T(plant). These findings showed little
      evidence of strong, direct positive canopy effects to soil moisture and attendant
      plant performance. Rather, it seems understory conditions foster competitive
      dominance by drought-tolerant species, and that positive and negative canopy
      effects on soil moisture and community and ecosystem processes depends on a suite
      of interacting biotic and abiotic factors.

PMID- 20809409
TI  - ECG-gated dual-source CT for detection of left atrial appendage thrombus in
      patients undergoing catheter ablation for atrial fibrillation.
AB  - PURPOSE: Left atrial ablation is increasingly used to treat patients with
      symptomatic atrial fibrillation (AF). Prior to ablation, exclusion of left atrial
      appendage (LAA) thrombus is important. Whether ECG-gated dual-source computed
      tomography (DSCT) provides a sensitive means of detecting LAA thrombus in
      patients undergoing percutaneous AF ablation is unknown. Thus, we sought to
      determine the utility of ECG-gated DSCT in detecting LAA thrombus in patients
      with AF. METHODS: A total of 255 patients (age 58 +/- 11 years, 78% male,
      ejection fraction 58 +/- 9%) who underwent ECG-gated DSCT and transesophageal
      echocardiography (TEE) prior to AF ablation between February 2006 and October
      2007 were included. CHADS2 score and demographic data were obtained
      prospectively. Gated DSCT images were independently reviewed by two cardiac
      imagers blinded to TEE findings. The LAA was either defined as normal (fully
      opacified) or abnormal (under-filled) by DSCT. RESULTS: An under-filled LAA was
      identified in 33 patients (12.9%), of whom four had thrombus confirmed by TEE.
      All patients diagnosed with LAA thrombus using TEE also had an abnormal LAA by
      gated DSCT. Thus, sensitivity and specificity for gated DSCT were 100% and 88%,
      respectively. No cases of LAA filling defects were observed in patients <51 years
      old with a CHADS2 of 0. CONCLUSION: In patients referred for AF ablation,
      thrombus is uncommon in the absence of additional risk factors. Gated DSCT
      provides excellent sensitivity for the detection of thrombus. Thus, in AF
      patients with a CHADS2 of 0, gated DSCT may provide a useful stand-alone imaging
      modality.

PMID- 20809410
TI  - Antioxidant capacity of alcalase hydrolysates and protein profiles of two
      conventional and seven low glycinin soybean cultivars.
AB  - Soy protein hydrolysates are considered a potential dietary source of natural
      antioxidants with important biological activities. This study was conducted to
      compare the effect of two conventional and seven low glycinin soybean cultivars
      on the antioxidant capacity (AC) of soy hydrolysates. Nine cultivars were grown
      in Bloomington, IL, Findlay, OH and Huxley, IA. The hydrolysates were produced
      enzymatically using alcalase and analyzed for AC using oxygen radical absorbance
      capacity (ORAC) assay and soluble protein. Statistical differences were observed
      in the protein profiles and AC among the different cultivars tested (P < 0.05).
      The hydrolysate from low glycinin cultivar 3 enriched in beta-conglycinin, grown
      in Bloomington, exhibited the highest AC, compared to the other cultivars across
      all locations. On average, soy cultivars rich in BC and purified BC hydrolysates
      (36.2 and 31.8 MUM Trolox equivalents (TE)/MUg soluble protein, respectively) (P
      > 0.05) had higher AC than purified glycinin (GL) hydrolysate (28.5 MUM TE/MUg
      soluble protein) (P < 0.05). It was possible to select a soybean cultivar that
      produced a higher antioxidant capacity upon alcalase hydrolysis.

PMID- 20809411
TI  - Multidirectional time-dependent effect of sinigrin and allyl isothiocyanate on
      metabolic parameters in rats.
AB  - Sinigrin (SIN) and allyl isothiocyanate (AITC) are compounds found in high
      concentrations in Brassica family vegetables, especially in Brussels sprouts.
      Recently, they have been used as a nutrition supplement for their preventive and
      medicinal effect on some types of cancer and other diseases. In this research,
      nutritional significance of parent glucosinolate sinigrin 50 MUmol/kg b. w./day
      and its degradation product allyl isothiocyanate 25 MUmol/kg b. w./day and 50
      MUmol/kg b. w./day was studied by the evaluation of their influence on some
      parameters of carbohydrate and lipid metabolism in an animal rat model in vivo
      after their single (4 h) and 2 weeks oral administration. Additionally, the aim
      of this trial was to evaluate the direct action of AITC on basal and epinephrine
      induced lipolysis in isolated rat adipocytes at concentration 1 MUM, 10 MUM and
      100 MUM in vitro. Sole AITC after 4 h of its ingestion caused liver
      triacylglycerols increment at both doses and glycaemia only at the higher dose.
      Multiple SIN treatment showed its putative bioconversion into AITC. It was found
      that SIN and AITC multiple administration in the same way strongly disturbed
      lipid and carbohydrate homeostasis, increasing esterified and total cholesterol,
      free fatty acids and lowering tracylglycerols in the blood serum. Additionally,
      AITC at both doses elevated insulinaemia and liver glycogen enhancement. The in
      vitro experiment revealed that AITC potentiated basal lipolysis process at 10
      MUM, and had stimulatory effect on epinephrine action at 1 MUM and 10 MUM. The
      results of this study demonstrated that the effect of SIN and AITC is
      multidirectional, indicating its impact on many organs like liver as well as
      pancreas, intestine in vivo action and rat adipocytes in vitro. Whilst
      consumption of cruciferous vegetables at levels currently considered "normal"
      seems to be beneficial to human health, this data suggest that any large increase
      in intake could conceivably lead to undesirable effect. This effect is
      potentiated with time of action of the examined compounds, whose influence is
      rather adverse for the majority of metabolic pathways (liver steatosis at short
      duration and insulinaemia, cholesterolaemia at long time treatment). Beneficial
      action of AITC concerned intensified hydrolysis of TG in the blood serum with a
      simultaneous lipolysis in adipocytes.

PMID- 20809412
TI  - Role of sorafenib and sunitinib in the induction of expressions of NKG2D ligands
      in nasopharyngeal carcinoma with high expression of ABCG2.
AB  - BACKGROUND: Sorafenib and sunitinib are novel small molecule tyrosine kinase
      inhibitors with multiple targets on tumor cells, which have been demonstrated to
      be beneficial in the treatment of several carcinomas. Combining the usage of
      molecular targeted agents and adoptive cellular immunotherapy (ACI) against drug
      resistant relapse nasopharyngeal carcinoma which had no standard therapeutic
      regimen was investigated by our research in order to study whether synergistic
      effects exist and related mechanisms. METHODS: Human multidrug-resistant
      nasopharyngeal carcinoma cell line CNE2/DDP with high and low expressions of
      ABCG(2) (abbreviated to ABCG (2) (High) CNE2/DDP and ABCG (2) (Low) CNE2/DDP)
      cells and NK cells were isolated by magnetic activated cell sorting, and the
      purity of isolated cells was detected by flow cytometry. mRNA expressions of drug
      resistant gene ABCG(2), Bcl-2, MDR1, MRP and MGMT in ABCG (2) (High) CNE2/DDP and
      ABCG (2) (Low) CNE2/DDP cells were detected by reverse transcription polymerase
      chain reaction (RT-PCR). Drug sensitivity of two kinds of cells to fluorouracil,
      cisplatin, vincristine, carboplatin, epirubicin, daunorubicin, paclitaxel,
      mitomycin, sorafenib, and sunitinib were detected by MTT assay. FCM was used to
      evaluate the expressions of NKG2D ligands (NKG2DLs,) on target cells before and
      after incubated with sorafenib and sunitinib. Subsequently, the cytotoxic
      sensitivity of incubated and un-incubated ABCG (2) (High) CNE2/DDP and ABCG (2)
      (Low) CNE2/DDP cells to NK cells was measured by CytoTox 96((r)) Non-Radioactive
      Cytotoxicity Assay. RESULTS: The results revealed that target cells' cytotoxic
      sensitivity to natural killer (NK) cells increased in association with up
      regulation of NKG2DLs on tumor cells after incubation with sorafenib and
      sunitinib. Furthermore, up-regulation in sunitinib group was much higher than in
      sorafenib group when it came to the expressions of NKG2DLs on tumor cells. For
      another, ABCG (2) (High) CNE2/DDP was much more sensitive to the regulation than
      ABCG (2) (Low) CNE2/DDP. CONCLUSIONS: Our research revealed for the first time
      that sorafenib and sunitinib could up-regulate NKG2DLs on tumor cells resulting
      in markedly increased tumor cells cytotoxic sensitivity to NK cells, which
      suggested that combining usage of molecular targeted agents and ACI may result in
      great benefits in clinical practice for the therapy-resistant cases and drug
      resistant relapse.

PMID- 20809413
TI  - Effects of stretching on morphological and biochemical aspects of the
      extracellular matrix of the rat calcaneal tendon.
AB  - Several studies have demonstrated the relationship between exercise and the
      extracellular matrix of muscle tendons, and have described alterations in their
      structural and biochemical properties when subjected to strenuous exercise.
      However, little is known about what happens to tendons when they are subjected to
      stretching. We evaluated the changes in the composition and structure of rat
      calcaneal tendons subjected to a stretching program. The animals had their
      muscles stretched for 30 s with 30 s of rest, with 10 repetitions, three and five
      times a week for 21 days. For morphological analysis, the sections were stained
      with hematoxylin-eosin and toluidine blue. For biochemical analysis, the tendons
      were treated with 4 M guanidine hydrochloride and analyzed in SDS-PAGE. The
      contents of total proteins and glycosaminoglycans were also measured. In the
      sections stained with toluidine blue, we could observe an increase of rounded
      cells, especially in the enthesis region. In the region next to the enthesis was
      a metachromatic region, which was more intensely stained in the stretched groups.
      In the tension regions, the cells appeared more aligned. Cellularity increased in
      both regions. The SDS-PAGE analysis showed a larger amount of collagen in the
      stretched groups and a polydispersed component of 65 kDa in all the groups. The
      amounts of proteins and glycosaminoglycans were also larger in the stretched
      tendons. The agarose-gel electrophoresis confirmed the presence of dermatan
      sulfate in the tension and compression regions, and of chondroitin sulfate only
      in the latter. Our results showed that the stretching stimulus changed the
      cellularity and the amount of the extracellular matrix compounds, confirming that
      tendons are dynamic structures with a capacity to detect alterations in their
      load.

PMID- 20809414
TI  - Avian toll-like receptors.
AB  - Analysis of the genomes of two distantly related bird species, chicken and zebra
      finch (divergence of about 100 million years), indicate that there are ten avian
      toll-like receptors and that five of these, TLR2a, 2b, 3, 4, 5 and 7, are clear
      orthologs to TLRs found in mammals. Duplication of genes has led to TLR1La and
      1Lb, TLR2a and 2b, and two TLR7s in the zebra finch. Avian TLR21 may be
      orthologous to TLR21 found in fish and amphibians, and avian TLR15, which is
      phylogenetically related to the TLR2 family, appears to be unique to avian
      species. While TLR2 is conserved between mammalian and avian species, the other
      TLR2 family members evolved independently. Dimerization between either of the two
      avian TLR2 species and TLR1La or 1Lb permits recognition of the same broad range
      of molecules as recognized by mammalian TLR2 dimerized with either TLR1, 6 and
      10. Similarly, while TLR9 has been lost from the avian genome, DNA high in
      unmethylated CpG motifs is immunostimulatory through avian TLR21 which is absent
      in mammals. Thus, while some TLR members were commonly retained in both mammals
      and birds, others were separately lost or gained, or diverged independently; but
      broadly speaking the TLRs of the two classes of vertebrates evolved to recognize
      very similar spectra of microbial products. Components of downstream TLR
      signaling are also mostly conserved but with some losses in avian species;
      notably, TRAM is absent in avian genomes and, hence, the TRIF/TRAM-dependent
      signaling pathway utilized by mammals in LPS activation appears to be absent in
      birds.

PMID- 20809415
TI  - Length difference between equine ZFX and ZFY genes and its application for
      molecular sex determination.
AB  - PURPOSE: we analyzed the sex chromosome-encoding ZFX-ZFY genes and tested
      molecular sexing using the amplification patterns of intron 9 of ZFX-ZFY in the
      horse. METHODS AND RESULTS: the amplification of the ZFX-ZFY produced two
      distinct patterns, reflecting sexual dimorphism based on a length difference
      between the X and Y chromosomes. The amplification products from foals showed two
      distinct bands: one was common to all foals and mares, indicating that this band
      was amplified from ZFX, while the other was specific to some foals, indicating
      that it was from ZFY. The result based on the PCR assay was identical to the
      results of amplification of the Y chromosome-specific SRY gene and those of
      investigations of the phenotypic gender in three different horse populations.
      CONCLUSION: we suggest that this PCR strategy for determining sexes by comparing
      the amplification patterns of ZFX-ZFY genes is a convenient and precise method
      for discriminating sexes in horses.

PMID- 20809416
TI  - Analysis and difference of voltage-dependent anion channel mRNA in ejaculated
      spermatozoa from normozoospermic fertile donors and infertile patients with
      idiopathic asthenozoospermia.
AB  - PURPOSE: to analyze the abundance and difference of voltage-dependent anion
      channel (VDAC) mRNA in ejaculated spermatozoa from normozoospermic fertile donors
      and infertile patients with idiopathic asthenozoospermia. METHODS: high motile
      and low motile spermatozoa were separated respectively from ejaculates of 36
      donors and 40 patients using a discontinuous Percoll gradient centrifugation.
      Real-Time PCR was performed to detect mRNA abundance and difference of three VDAC
      subtypes between two groups with different sperm motility. RESULTS: real-Time PCR
      demonstrated that three VDAC mRNAs were present in mature spermatozoa. The VDAC2
      mRNA level in ejaculated spermatozoa of patients was significantly higher than
      that of donors. No significant differences of VDAC1 and VDAC3 mRNA levels were
      found between two groups. CONCLUSION: the high abundance of VDAC2 mRNA seemed to
      have a positive correlation with low sperm motility. The abnormal expression of
      VDAC might be related to male infertility with idiopathic asthenozoospermia.

PMID- 20809417
TI  - In vitro antimalarial activity of medicinal plant extracts against Plasmodium
      falciparum.
AB  - Malaria is a major global public health problem, and the alarming spread of drug
      resistance and limited number of effective drugs now available underline how
      important it is to discover new antimalarial compounds. In the present study, ten
      plants were extracted with ethyl acetate and methanol and tested for their
      antimalarial activity against chloroquine (CQ)-sensitive (3D7) and CQ-resistant
      (Dd2 and INDO) strains of Plasmodium falciparum in culture using the fluorescence
      based SYBR Green assay. Plant extracts showed moderate to good antiparasitic
      effects. Promising antiplasmodial activity was found in the extracts from two
      plants, Phyllanthus emblica leaf 50% inhibitory concentration (IC50) 3D7: 7.25
      MUg/mL (ethyl acetate extract), 3.125 MUg/mL (methanol extract), and Syzygium
      aromaticum flower bud, IC50 3D7:13 MUg/mL, (ethyl acetate extract) and 6.25
      MUg/mL (methanol extract). Moderate activity (30-75 MUg/mL) was found in the
      ethyl acetate and methanol extracts of Abrus precatorius (seed) and Gloriosa
      superba (leaf); leaf ethyl acetate extracts of Annona squamosa and flower of Musa
      paradisiaca. The above mentioned plant extracts were also found to be active
      against CQ-resistant strains (Dd2 and INDO). Cytotoxicity study with P. emblica
      leaf and S. aromaticum flower bud, extracts showed good therapeutic indices.
      These results demonstrate that leaf ethyl acetate and methanol extracts of P.
      emblica and flower bud extract of S. aromaticum may serve as antimalarial agents
      even in their crude form. The isolation of compounds from P. emblica and S.
      aromaticum seems to be of special interest for further antimalarial studies.

PMID- 20809418
TI  - Immune detection of acetylcholinesterase in subcellular compartments of
      Trypanosoma evansi.
AB  - Trypanosoma evansi is a worldwide distributed hemoparasite with a strong economic
      impact in veterinary activities. Despite widespread knowledge about the etiology
      of the disease caused by T. evansi, there are few detailed studies about the
      metabolism of this parasite. The aim of this study was to determine the presence
      of Acetylcholinesterase (AChE) in T. evansi through a strategy of subcellular
      localization and confocal microscopy. The localization of the AChE by
      differential and isopycnic centrifugation strategy showed that this enzyme has a
      predominant localization in the glycosome, similar to hexokinase, and it is not
      present in either the cytosol or the plasma membrane. This study shows novel data
      that help to understand the non-neuronal role of AChE in the Trypanosomatidae
      family.

PMID- 20809419
TI  - Strong expression of TGF-beta in human host tissues around subcutaneous
      Dirofilaria repens.
AB  - Dirofilaria repens and other Dirofilaria species are widely distributed parasitic
      nematodes of carnivores, which occasionally are transmitted to men, causing
      subcutaneous nodules. In humans, it usually occurs only as single male or female
      filariae without production of microfilariae. The non-productive living or dead
      Dirofilaria worms in subcutaneous biopsies from 15 human patients permitted us to
      study the role of the pleiotropic and immunoregulatory cytokine transforming
      growth factor beta (TGF-beta) independent from the influence of microfilariae.
      Antiserum against latent TGF-beta 1 was used for an immunohistological
      examination. In the infiltrates around female and male filariae, there occurred
      strongly TGF-beta-positive macrophages, mast cells, endothelial cells,
      fibrocytes, and giant cells adjacent to dead worms. In one nodule, secondary
      lymph follicles were observed with clearly TGF-beta-positive B cells in the
      mantle zone and weakly positive macrophages and B cells in the germinal centre. A
      network of CD35-positive follicular dendritic cells was observed in the germinal
      centre. All Dirofilaria contained Wolbachia endobacteria, which probably had
      attracted the numerous TGF-beta-negative neutrophils near to the worm. Wolbachia
      were phagocytosed by neutrophils adjacent to dead filariae. Macrophages and
      lymphocytes expressed the MHC class II molecule HLA-DR in small accumulations of
      immune cells in the outer zone of the infiltrate and the mantle zone and germinal
      centre of secondary lymph follicles. It is concluded that single non-productive
      Dirofilaria worms elicit a strong expression of TGF-beta. This result is in
      accordance with observations on Onchocerca volvulus from patients with the
      hyporeactive (generalised) form.

PMID- 20809420
TI  - Development of improved methods for delivery of Trichuris muris to the laboratory
      mouse.
AB  - Murine immunological responses to experimental infection with Trichuris muris and
      the effects of the resident microbiota on these responses are of increasing
      interest. For these studies, accurate dose delivery and improved sterilization of
      inocula are essential to prevent co-infection with unknown contaminants. We found
      that washing T. muris eggs with antibiotics may not be sufficient for
      sterilization of inocula. However, washing eggs in 6.25% hypochlorite/bleach
      eliminated bacteria and fungi, as determined by culture and PCR, did not harm
      viable T. muris eggs and reduced the number of non-viable eggs in the inocula. A
      hatching assay and propidium iodide staining method were developed and found to
      increase the accuracy for assessing T. muris egg viability prior to infection for
      rapid dose evaluation. In addition, metal gavage feeding needles increased the
      accuracy and precision of the dose delivered to the mice compared to flexible
      rubber tubes. These methods will improve experimental Trichuris studies by
      decreasing the variability in outcome due to unintended carryover of adherent
      microorganisms and unrecognized variation in inocula.

PMID- 20809421
TI  - A study on nm23-H1 expression in diffuse large B-cell lymphoma that was treated
      with CyclOBEAP plus rituximab therapy.
AB  - In our previous study on nm23-H1 expression with diffuse large B-cell lymphoma
      (DLBCL), we found that patients with positive nm23-H1 had significantly poorer
      prognosis than patients with negative nm23-H1. We examined whether nm23-H1 is a
      prognostic factor of DLBCL in the rituximab era. The subjects were 101 DLBCL
      patients who underwent R-CyclOBEAP (rituximab, cyclophosphamide, vincristine,
      bleomycin, etoposide, doxorubicin, and prednisolone) therapy and in whom markers
      could be analyzed. We evaluated CD5, CD10, BCL2, BCL6, MUM1, and nm23-H1
      expression by immunohistochemistry. Ninety-four DLBCL patients who underwent
      CyclOBEAP therapy were assumed as historical controls. Among DLBCL patients who
      underwent CyclOBEAP therapy, BCL2 positivity, MUM1 positivity, non-germinal
      center B-cell (non-GCB), and nm23-H1 positivity were associated with
      significantly shorter overall survival (OS) and progression-free survival (PFS).
      On the other hand, among DLBCL patients who underwent R-CyclOBEAP therapy, the 5
      year OS rates of the nm23-H1-positive DLBCL (n = 32) and nm23-H1-negative DLBCL
      groups (n = 69) were 65% and 97%, respectively (p = 0.001), with 5-year PFS rates
      of 51% and 89%, respectively (p = 0.001). In the rituximab era, BCL2, MUM1, and
      non-GCB were not prognostic factors. We demonstrated that among patients with
      DLBCL who underwent R-CyclOBEAP therapy, patients with nm23-H1 expression had a
      significantly poorer prognosis than patients without nm23-H1 expression. These
      results suggest an important role for nm23-H1 in malignant progression and a
      potential therapeutic target for DLBCL.

PMID- 20809422
TI  - Palliative care for patients with hematological malignancies-a case series.

PMID- 20809423
TI  - A modified regimen of pegylated liposomal doxorubicin, bortezomib, and
      dexamethasone is effective and well tolerated in the treatment of relapsed or
      refractory multiple myeloma.
AB  - Preclinical and clinical studies have demonstrated synergy between bortezomib and
      pegylated liposomal doxorubicin (PLD) for relapsed/refractory (R/R) multiple
      myeloma (MM) patients compared to bortezomib as a single agent. This
      retrospective study evaluated the efficacy and safety of a more frequent low-dose
      schedule of PLD, bortezomib, and intravenous dexamethasone (DVD) for patients
      with R/R MM, many of whom were previously treated with bortezomib. Twenty-eight
      patients with R/R MM were treated, and 23 (83%) had been previously treated with
      >= 1 bortezomib-containing regimen. Treatment consisted of dexamethasone 40 mg
      intravenously, bortezomib 1.0 mg/m(2), and PLD 5.0 mg/m(2) on days 1, 4, 8, and
      11 of a 28-day cycle for a maximum of eight cycles. Patients ranged from 33 to 81
      years of age (median, 67) and had received 1-14 prior therapies (median, 5). At
      baseline, ten, nine, and nine patients were in stages I, II, and III,
      respectively, as defined by the International Staging System, and eight (29%)
      patients had elevated serum creatinine levels. The overall response rate was 61%,
      which included one (4%) complete response, three (11%) very good partial
      responses, eight (29%) partial responses, and five (18%) minimal responses. Of
      the 23 patients who had previously received bortezomib, 12 (52%) responded. The
      regimen was well tolerated with only six patients (21%) who showed worsening of
      their baseline peripheral neuropathy (PN). One patient discontinued this regimen
      due to an adverse event (grade II PN). DVD appears to represent a well-tolerated
      regimen with a high response rate for the treatment of R/R MM patients.

PMID- 20809424
TI  - Hyperfibrinogenemia after preoperative chemoradiotherapy predicts poor response
      and poor prognosis in rectal cancer.
AB  - PURPOSE: Although hyperfibrinogenemia has been reported in patients with
      colorectal cancer, neither its clinical implications nor the effect of
      chemoradiotherapy (CRT) on the fibrinogen levels have been fully investigated. We
      investigated the clinical significance of pre- and post-CRT fibrinogen levels in
      patients with rectal cancer. METHODS: The medical records of 82 patients with
      rectal cancer, who had received CRT followed by surgical resection, were
      retrospectively reviewed. The correlation between the clinicopathological
      variables and the pre- and post-CRT plasma fibrinogen levels, and that between
      the changes of fibrinogen, C-reactive protein (CRP), or carcinoembryonic antigen
      (CEA) levels after CRT and the pathological tumor regression grading was
      analyzed. Furthermore, the impact of post-CRT fibrinogen levels on the prognosis
      of these patients was assessed. RESULTS: Plasma fibrinogen markedly decreased
      after CRT. The post-CRT fibrinogen level significantly correlated with lymphatic
      invasion, venous invasion, tumor size, depth of invasion, and the pathological
      tumor regression grading. The CRT-induced pathological tumor regression grading
      well correlated with the decrease of fibrinogen level, but not with that of CRP
      or CEA. Furthermore, patients with high post-CRT fibrinogen had significantly
      shorter disease-free survival. CONCLUSIONS: Reduction of plasma fibrinogen
      induced by CRT should be a promising biomarker for evaluating the efficacy of CRT
      in rectal cancer patients.

PMID- 20809425
TI  - Electrical field stimulation promotes anastomotic healing in poorly perfused rat
      colon.
AB  - INTRODUCTION: Hypoperfusion of the bowel is a risk factor for anastomotic
      failure. Electrical field stimulation has been shown to improve repair in
      ischemic tissue, but its influence in hypoperfused colon has not been
      investigated. The hypothesis of this experimental animal study was that
      electrical field stimulation improves anastomotic healing in ischemic bowel.
      MATERIALS AND METHODS: Thirty rats were divided evenly into three groups:
      control, ischemia/placebo, and ischemia/test group. Ischemia was induced by
      ligation of the arterial supply to the proximal colon. The watershed area was
      identified and transected. Field stimulation was achieved by application of
      negatively charged diethylaminoethyl Sephadex beads in methylcellulose gel to the
      colonic epithelium prior to anastomosis. The placebo group had methylcellulose
      gel only applied and control animals had anastomosis only. Anastomotic strength
      was measured using anastomotic bursting pressure and hydroxyproline content.
      Systemic effect was investigated via interleukin-6 and vascular endothelial
      growth factor assay. RESULTS: The ischemia/electrical field stimulation (EFS)
      group had significantly increased bursting pressure and hydroxyproline content in
      comparison with the placebo group (P < 0.001). Serum cytokine levels were
      unaffected. CONCLUSION: Negatively charged EFS improves anastomotic healing in
      hypoperfused colon without induction of systemic cytokines and has potential as a
      local treatment in high-risk bowel anastomosis.

PMID- 20809426
TI  - Prognostic significance of response to preoperative radiotherapy, lymph node
      metastasis, and CEA level in patients undergoing total mesorectal excision of
      rectal cancer.
AB  - PURPOSE: The aim of this study was to investigate the prognostic significance of
      the response of primary rectal lesions to preoperative radiotherapy, pathological
      nodal status, and carcinoembryonic antigen (CEA) levels before and after
      radiotherapy in rectal cancer patients treated with a total mesorectal excision.
      METHODS: We investigated the prognostic significance of the clinical and
      pathological factors in 97 patients treated with preoperative radiotherapy (50
      50.4 Gy over 5-6 weeks) followed by curative resections. RESULTS: A high CEA
      level (>5 ng/mL) after radiotherapy (hazard ratio, 2.849; 95% confidence
      interval, 1.061-7.651; p = 0.0377) and pathological lymph node metastasis (hazard
      ratio, 0.350; 95% confidence interval, 0.154-0.797; p = 0.0124) were
      independently associated with postoperative recurrence. Although the CEA level
      before radiotherapy was associated with disease-free survival in a univariate
      analysis, it lost its statistical significance in a multivariate analysis. The
      response of the primary rectal lesions, evaluated pathologically by T stage and
      the degree of regression, was not associated with disease-free survival. In
      patients without lymph node metastasis, the 5-year disease-free survival of those
      with a high CEA level after radiotherapy was significantly worse than those with
      low CEA after radiotherapy (61.6% vs. 89.0%, respectively, p = 0.0234).
      CONCLUSIONS: Pathological lymph node metastasis and a high CEA level after
      radiotherapy were independent predictors of a poor outcome in rectal cancer
      patients treated with preoperative radiotherapy. The CEA level after radiotherapy
      was capable of discriminating patients with a high risk of recurrence among
      pathologically node-negative patients.

PMID- 20809427
TI  - Human papillomavirus and colorectal cancer: evidences and pitfalls of published
      literature.
AB  - PURPOSE: The aim of this study is to review published literature regarding a
      possible role of human papillomavirus (HPV) infection in colorectal cancer in
      order to understand if HPV infection plays an active role in colorectal
      carcinogenesis and to highlight evidences and pitfalls of published studies.
      METHODS: We reviewed literature by searching PubMed, Ovid, and the Cochrane
      databases for published series investigating HPV and colorectal cancer from 1988
      to date. RESULTS: Twenty-one studies investigating a possible correlation between
      HPV infection and colon cancer have been published. We reviewed 15 case-control
      studies and six studies investigating a possible role for HPV virus in colorectal
      carcinogenesis. HPV was detected in the majority of reported series with a
      significant difference in HPV infection between tumors and disease-free controls
      or tumor-adjacent tissue; the HPV mean detection rate within carcinomas was
      41.7%, comparing to a mean detection rate of 32.8% in adjacent colic mucosae, and
      5.8% in disease-free controls (Chi-square test, p = 0.001). The correlation
      between HPV infection and c-myc amplification, k-ras mutation, and p53
      polymorphism or mutations has been investigated; however, the possible role of
      HPV in colorectal carcinogenesis was not defined. CONCLUSIONS: HPV has been
      detected in the majority of reported series, but published literature lacks in
      definitive data regarding standard methods of investigation and stratification of
      groups and population. These data encourage further studies with the aim to
      investigate the presence of the virus in larger series, its possible role in
      oncogenesis, the integration in host genome, the expression of viral
      oncoproteins, the mutations in HPV positive cancers and routes of colon infection
      (hematologic/lymphatic spreading or perineal diffusion).

PMID- 20809434
TI  - Excess weight in the canton of Zurich, 1992-2009: harbinger of a trend reversal
      in Switzerland?
AB  - BACKGROUND/OBJECTIVE: In Switzerland, as in most developed countries, there has
      been a growing prevalence of excess weight in recent decades. However, within the
      country there may be regional variations. We investigated whether the trends in
      excess weight prevalence in the largest urban region differed from that in the
      rest of German Switzerland (GS). METHODS: We used individual data from four
      nationally representative Swiss Health Surveys (1992-2007) and from one survey
      conducted in the Canton of Zurich (ZH) in 2009. All studies used self-reported
      height and weight (18-74 years, N = 41 628). Prevalence rates of excess weight
      (BMI > or = 25 kg/m2) were age standardised and population weighted. Odds ratios
      (OR: normal vs. excess weight) were obtained with weighted multivariable logistic
      regression. RESULTS: The prevalence of excess weight was lower in ZH than in GS,
      with increasing differences over time. In GS, OR increased in men (p trend 1992
      2007 <0.001) and stagnated in women. In contrast, in ZH, OR stagnated in men and
      decreased in women (p trend 1997-2009 = 0.005). Within ZH, compared to the
      capital city, OR were higher in men in the less privileged part of the
      Metropolitan Area (p = 0.046) and in women not living in the Zurich Metropolitan
      Area (p = 0.049). CONCLUSION: In ZH, the prevalence of excess weight stagnated in
      men and decreased after having reached a peak in 1997 in women. This is the first
      study showing a decrease in Swiss adults, a population with internationally low
      excess weight prevalence. There is room for speculation whether ZH is a harbinger
      of the future situation in other regions of Switzerland and possibly other
      developed countries.

PMID- 20809435
TI  - Making pulmonary rehabilitation a success in COPD.
AB  - A truly successful pulmonary rehabilitation entails implementing physical
      activity maintenance. This article reviews the current knowledge on pulmonary
      rehabilitation and the expected benefits, the setting, the relationship between
      self-management and pulmonary rehabilitation, in order to develop and implement
      clinically-effective physical activity maintenance interventions. The
      effectiveness of pulmonary rehabilitation is well-established. However, access to
      pulmonary rehabilitation is limited. Home-based pulmonary rehabilitation has been
      shown to be an effective, equivalent alternative to outpatient pulmonary
      rehabilitation in COPD patients. The opportunity to offer different pulmonary
      rehabilitation settings tailored to individual needs should improve accessibility
      to this intervention. Sustained long-term physical activity remains the most
      important challenge for COPD patients. We need a dependable system of coordinated
      health care interventions and communication, and components that include self
      management support. Self-management should be an integrated part of pulmonary
      rehabilitation and remain long after the pulmonary rehabilitation is completed.
      By early identification of patients who may have difficulty maintaining exercise
      and implementing appropriate self-management interventions during and after the
      rehabilitation program, it may be possible to promote better long-term
      involvement in physical activity. Pulmonary rehabilitation should not stand
      alone; the best program is that which can be maintained to translate into a
      continuous increase in the activities of daily living. Future research should
      evaluate the effect of self-management interventions combined with pulmonary
      rehabilitation to improve long-term activity and exercise maintenance.

PMID- 20809428
TI  - Clinician- and patient-reported long-term evaluation of screw- and cement
      retained implant restorations: a 5-year prospective study.
AB  - The purpose of this study was to evaluate the survival and success of screw-
      versus cement-retained implant crowns over a 5-year period. This was a multi
      center prospective cohort study, consisting of patients who had >=1 dental
      implant placed and restored in the anterior maxilla over a 5-year period. The
      primary predictor variable was the type of restoration (screw- versus cement
      retained). The outcome variables were clinician- or patient-reported measures
      related to soft tissue and restoration quality. Descriptive and bivariate
      statistics were computed to compare the screw- versus cement-retained groups.
      Kaplan-Meier statistics were computed for implant survival. Information was
      collected for 102 patients who had 214 implants placed during the study period.
      Complete data, amenable to analysis, were available for 99 (97.1%) patients and
      193 (90.2%) implants. The restorations were approximately evenly divided between
      screw- (53.4%) and cement-retained (46.6%). Approximately 49% of patients in the
      sample were female; the sample's mean age was 47.3 +/- 13.9 years; each patient
      had an average of 2.0 +/- 1.0 implants placed and restored. The mean time from
      prosthesis placement (definitive) to study endpoint was 61.9 +/- 10.6 months. The
      overall implant survival rate was 96.4%, with no statistically significant
      difference in survival between the screw- and cement-retained groups (p = 0.45).
      The majority of clinician- and patient-assessed outcomes were similar. The
      results of this study indicate that for the majority of clinician- and patient
      assessed success parameters screw- and cement-retained restorations are
      equivalent in the anterior maxilla.

PMID- 20809436
TI  - Electronic cardiac medicine: present and future opportunities.
AB  - The second half of the 20th century witnessed a revolution in electronic medicine
      similar to that in pharmacology in the decades before. The advent of the
      implantable pacemaker, implantable cardioverter-defibrillators, cardiac
      resynchronisation therapies, insertable loop recorders and more, have improved
      diagnoses and reduced mortality and morbidity in millions of patients suffering
      from cardiac disease. The possibility to monitor patients continually without
      need for frequent office visits has the potential to reduce follow-up burden on
      physicians, facilitate increased use of home-based care and further improve the
      safety for patients. This review summarises the role of cardiac device therapies
      today and some of the developments which we can hope for in the nearest future.

PMID- 20809437
TI  - Trend of burnout among Swiss doctors.
AB  - QUESTION UNDER STUDY: Over the last decade the Swiss health care system has
      undergone several changes, resulting in stronger economic constraints, a heavier
      administrative workload and limited work autonomy for doctors. In this context we
      examined the change in burnout prevalence over time among Swiss doctors surveyed
      during this period. METHODS: Cross-sectional survey data collected by mail in
      2002, 2004 and 2007 throughout the country were used. Measures included the
      Maslach Burnout Inventory (MBI), several socio-demographics (gender, living
      alone, having children), and work-related characteristics (number of years in
      current workplace, hours worked). Answers to the MBI were used to classify
      respondents into moderate (high score on either the emotional exhaustion or the
      depersonalisation/cynicism subscale) and high degree of burnout (scores in the
      range of burnout in all three scales). RESULTS: Rates of moderate-degree burnout
      increased from 33% to 42% among general practitioners (p = 0.002) and from 19% to
      34% among paediatricians (p = 0.001) (high degree of burnout: 4% to 6% [p = 0.17]
      and 2% to 4% [p = 0.42] respectively). After adjustment for significant socio
      demographic and work-related characteristics, an increased risk of moderate
      burnout was found for doctors surveyed in 2004 and 2007 (OR 1.6, 95%CI 1.3 to
      2.0), general practitioners (OR 1.6, 95%CI 1.3 to 2.0) and French-speaking
      doctors (OR 1.5, 95%CI 1.3 to 1.9). An increased risk of high-degree burnout was
      found only for general practitioners (OR 1.8, 95%CI 1.05 to 3.0). CONCLUSIONS:
      Burnout levels among Swiss doctors have increased over the last decade, in
      particular among French-speaking doctors.

PMID- 20809438
TI  - Chronic age-related diseases share risk factors: do they share pathophysiological
      mechanisms and why does that matter?
AB  - The World Health Organization (WHO) assigns high priority to the prevention of
      non-communicable age-related diseases such as heart disease, cancer, diabetes,
      stroke and chronic lower respiratory diseases. They are now the leading causes of
      death, in both industrialised and developing countries, mostly due to increased
      life expectancy and urbanisation with associated changes in lifestyle and
      environment. Tobacco smoking, physical inactivity and resulting obesity are
      established risk factors for many chronic diseases. Yet, the aetiology of age
      related diseases is complex and varies between individuals. This often makes it
      difficult to identify causal risk factors, especially if their relative effects
      are weak. For example, the associations of both obesity and air pollution with
      several age-related diseases remain poorly understood with regard to causality
      and biological mechanisms. Exposure to both, excess body fat and particulate
      matter, is accompanied by systemic low-grade inflammation as well as alterations
      in insulin/insulin-like growth factor signalling and cell cycle control. These
      mechanisms have also been associated in animal and some human studies with
      longevity and ageing in more general terms. In this paper, it is therefore
      hypothesised that they may, at least in part, be responsible for the adverse
      health effects of obesity and air pollution. It is argued that molecular and
      genetic epidemiology now offer novel instruments to improve the understanding of
      these pathophysiological pathways and their link to disease aetiology.
      Understanding the causality of exposure disease associations and differences in
      susceptibilities to environment and lifestyle is an important aspect for
      effective prevention.

PMID- 20809439
TI  - Overview of modern radiation therapy.

PMID- 20809440
TI  - CPRIT becomes a reality.

PMID- 20809441
TI  - The business of cancer care.

PMID- 20809442
TI  - Supporting cancer services.

PMID- 20809443
TI  - Cancer screening: controversies and opportunities.

PMID- 20809444
TI  - An update on endometrial cancer.

PMID- 20809446
TI  - An update on hematological malignancies.

PMID- 20809445
TI  - Current approach to breast cancer.

PMID- 20809447
TI  - Minimally invasive spine surgery.

PMID- 20809449
TI  - Long-term angiographic and histological results of a new hydrogel-containing
      filling coil in experimental rabbit aneurysms.
AB  - BACKGROUND: The aim of this study was to compare the performance of a new filling
      coil, the HydroFill device, to historical results of HydroSoft and bare platinum
      coil devices in experimental rabbit aneurysms. METHODS: Experimental aneurysms
      were constructed in rabbits and embolized with HydroFill (n=32), HydroSoft
      (n=48), or bare platinum coil (n=47) devices. Angiographic occlusion was
      evaluated post-treatment and at 1 month (n=55), 3 month (n=20), 6 month (n=35),
      and 12 month (n=12) follow-ups according to the Raymond scale. The aneurysms were
      analyzed histologically for neointima formation, thrombus organization, and
      inflammation. Continuous and discrete results were compared using ANOVA/t-test
      and chi (2) tests, respectively. RESULTS: Volumetric occlusion of the aneurysm
      sac was increased in the HydroFill group compared to the HydroSoft and platinum
      coil groups. Protrusions into the parent artery were common in all treatment
      groups due to the treatment of wide-necked aneurysms without the use of balloons
      or stents. Although angiographic occlusion post-treatment scores were reduced in
      the HydroFill group compared to the HydroSoft and platinum coil groups,
      stable/progressive occlusion was increased in the HydroFill group compared to the
      platinum coil group. Histologically, neointima formation and thrombus
      organization scores were increased in the HydroFill and HydroSoft groups compared
      to the platinum coil group at 3 months. Although there were some differences in
      the scoring, inflammation was generally minimal to mild in all three groups.
      CONCLUSION: The HydroFill device, with its high levels of volumetric filling,
      increased stable/progressive occlusion at follow-up, increased neointima
      formation, and increased thrombus organization, shows promise for clinical use.

PMID- 20809450
TI  - Endoscopic third ventriculostomy in patients with secondary triventricular
      hydrocephalus from a haemorrhage or ischaemia in the posterior cranial fossa.
AB  - BACKGROUND: The aim of this project was to evaluate the efficacy of endoscopic
      third ventriculostomy (ETV) in the treatment of acute hydrocephalus caused by a
      haemorrhage or ischaemia in the posterior cranial fossa. METHODS: 21 patients who
      had acute triventricular hydrocephalus resulting from ischaemia in 8 cases, and
      from cerebellar haemorrhage in 13 cases were treated with endoscopic third
      ventriculostomy. This series was compared with a control group of 30 patients,
      with clinical neuroradiological characteristics comparable to the preceding group
      (18 acute post-haemorrhage hydrocephalus and 12 post-ischaemia in the posterior
      cranial fossa), treated by external ventricular drainage (EVD). All patients were
      monitored clinically and by brain computed axial tomography (CT) to measure the
      dimensions of the lateral and third ventricles. The criteria used to define
      efficacy were based on the image of the postoperative cerebral CT scan. RESULTS:
      No patient suffered haemorrhagic complications from surgical procedures or
      additional neurological deficits. There was no postoperative mortality or added
      morbidity. In all cases there was an improvement of intracranial hypertension.
      Clinical improvement was associated with a reduction of the ventricular
      dimensions documented by serial CT scans. CONCLUSIONS: We consider that, in
      selected cases, ETV can be suggested as the first choice treatment instead of the
      classic EVD. In the overall management of such patients, ETV has no or a very low
      rate of complications and allows shorter hospitalisation and earlier transfer to
      rehabilitative structures.

PMID- 20809451
TI  - Posterior dynamic stabilization in the treatment of lumbar degenerative disc
      disease: 2-year follow-up.
AB  - BACKGROUND: A prospective pilot study was designed to evaluate the role of a
      posterior dynamic stabilization technique in the surgical treatment of
      degenerative disc disease. Posterior dynamic stabilization with a hinged screw is
      a new concept in the surgical treatment of degenerative disc disease of the
      lumbar spine. The traditional surgical treatment is to apply a fusion procedure.
      However, numerous reports showed unsatisfactory clinical outcomes even when
      patients have satisfactory radiological outcomes following fusion procedures.
      MATERIAL AND METHODS: The study included patients who were surgically treated
      with a dynamic stabilization technique due to painful degenerative disc disease.
      Clinical and radiological findings for the 20 participating patients were
      analyzed in a 2-year follow-up study. Preoperative and postoperative data at the
      3 (rd), 12 (th) and 24 (th) month were collected for both clinical and
      radiological outcomes. Statistical analyses between preoperative and
      postoperative data were performed using the Wilcoxon test. RESULTS: The clinical
      outcome measurements (VAS, ODI) showed significant improvement in all
      postoperative measurements compared to preoperative values. The mean preoperative
      visual analogue score (VAS, 7.9) and Oswestry Disability Index (ODI 59.2)
      significantly decreased to 0.8 for VAS and 9.2 for ODI, at 2 years post-operation
      (p<0.05). The radiological studies showed no significant changes between pre- and
      postoperative values, in all parameters. There was no mortality or morbidity.
      CONCLUSIONS: The results of this pilot study are encouraging. Dynamic
      stabilization may be an effective technique in the surgical treatment of painful
      degenerative disc disease. A larger series study, with longer follow-up periods
      and with control groups is needed to determine the success and safety of
      posterior dynamic stabilization in the surgical treatment of degenerative disc
      disease.

PMID- 20809452
TI  - Decompression and interspinous dynamic stabilization using the locker for lumbar
      canal stenosis associated with low-grade degenerative spondylolisthesis.
AB  - BACKGROUND: Decompression and spinal fusion have been generally recommended for
      spinal stenosis associated with low-grade degenerative spondylolisthesis (DS),
      although this is still controversial. The purpose of the present study is to
      analyze the clinical and radiological outcomes of interspinous dynamic
      stabilization using the Locker (WINNOVA co, Seoul, Korea) for lumbar canal
      stenosis with grade I DS. METHODS: The authors performed a retrospective review
      of 23 consecutive patients who underwent single level decompression and the
      Locker application for lumbar canal stenosis with grade I DS and were followed up
      for at least 2 years. Excluded were those with DS grade II or higher and DS
      combined with foraminal disc herniation/stenosis. The mean age of patients at the
      time of surgery was 62.1 years (range: 45-81 years). RESULTS: There were no
      complications in the perioperative period. At a mean follow-up duration of 28.3
      months (range: 24-32 months), visual analogue scale scores for back pain, leg
      pain, and Oswestry disability index had decreased significantly; from 4.6, 7.2,
      and 38.5% to 2.4, 2.6, and 15.3%, respectively. Clinical success was achieved in
      87% of the patients. The mean percentage of slippage did not change
      significantly. The mean sagittal rotation angle significantly decreased from 9.7
      to 6.5 degrees (p=0.01). One patient (4.3%) underwent secondary fusion surgery
      due to persistent pain. CONCLUSIONS: Decompression and interspinous dynamic
      stabilization using the Locker yielded favorable clinical and radiological
      outcomes for lumbar canal stenosis with grade I DS and could be an alternative
      for spinal fusion. However, further long-term follow-up studies are necessary.

PMID- 20809453
TI  - Minimally invasive approach for far lateral disc herniations: results from 20
      patients.
AB  - BACKGROUND: Far lateral lumbar disc herniations, while infrequent, are a
      substantial cause of morbidity causing painful radicular syndromes often
      accompanied by a motor or sensory deficit. Surgical treatment can be challenging
      technically because of unfamiliar lateral anatomy and the importance of adjacent
      osseous structures, notably the pars interarticularis and facet joint. METHOD:
      The traditional approach for a far lateral lumbar disc herniation involves a
      midline incision, wide lateral subperiosteal exposure and partial removal of
      these structures with the potential for iatrogenic instability. A paramedian
      approach to the lateral compartment of the disc space is advantageous because it
      directly targets the pathology. The use of recently developed minimally invasive
      retractor systems decreases tissue dissection and blood loss and improves
      postoperative recovery. RESULTS AND DISCUSSION: We present a series of 20
      patients who underwent far lateral discectomy using a minimally invasive muscle
      splitting approach.

PMID- 20809454
TI  - Transcorporeal tunnel approach for unilateral cervical radiculopathy: a 2-year
      follow-up review and results.
AB  - BACKGROUND: The long-term complications of traditional discectomy and fusion
      surgery have led to the need for minimally invasive procedures that do not
      require a complete discectomy and fusion. Jho developed an anterior unco
      foraminotomy that we have modified, with the approach being more medial than that
      of Jho, into an anterior transcorporeal tunnel approach which we use for cervical
      spondylotic unilateral radiculopathy. METHODS: A retrospective analysis was
      carried out in 30 patients who underwent a transcorporeal "tunnel" anterior micro
      foraminotomy for unilateral radicular symptoms with a follow-up more than 2
      years. All were operated by a single surgeon using the same technique from the
      vertebral body proximal to the lesion and proceeding downwards to the herniation.
      At final follow-up we reviewed the clinical and radiological results. RESULTS:
      All patients in the immediate post-operative period showed relief of their
      symptoms, and there were major complications. 3 patients complained about the
      numbness in the immediate postoperative period which resolved within 3 months.
      There was a significant improvement in NDI from pre-operative 55.16% to
      postoperative 5.82% ( P <0.001). Average pre-operative VAS scores for arm and
      neck were 8.15 and 4.05, respectively; which improved to 1.05 and 1.23 ( P
      <0.001) postoperatively. There was an average 9% decrease (from 7.8 mm to 7.3 mm)
      in the post-operative disc height compared to the preoperative disc height;
      however, it was clinically and radiologically insignificant. The long-term
      results were favourable and there were no major complications. CONCLUSION: The
      transcorporeal tunnel approach can be used as an alternative treatment for
      cervical spondylotic radiculopathy.

PMID- 20809455
TI  - Endoscopic clipping of a middle cerebral artery aneurysm in a middle fossa
      arachnoid cyst and review of the literature.
AB  - BACKGROUND: Arachnoid cysts are often associated with subdural hematoma following
      head trauma. The incidental finding of an aneurysma and a cyst is rare. We
      describe for the first time the treatment of such a case using endoscopic
      techniques. CASE REPORT: A 44-year-old man was admitted to our hospital with a
      mild headache and a hemifacial spasm attack at the right side of his face. The
      radiological examinations demonstrated bilateral slyvian fissure arachnoid cysts
      and an aneurysm with the dome projecting superolaterally, at the bifurcation of
      the right middle cerebral artery in the arachnoid cyst. The patient underwent a
      complete endoscopic surgical clipping of the aneurysm, and partial excision of
      the right cyst wall and bilateral fenestration to the basal cistern via a single
      burr-hole craniectomy at the right temporal region. The patient had an uneventful
      postoperative course without neurological impairment and complication. However,
      his complaints still persisted postoperatively. CONCLUSION: Endoscopic management
      of arachnoid cysts is an effective and less morbid treatment. This less invasive
      option might be safe for the clipping of aneurysms within an arachnoid cyst with
      no additional morbidity for the patient. With smaller operative exposures and yet
      better visualization offered, neuroendoscopy may reduce operative morbidity.

PMID- 20809456
TI  - Video-assisted thoracoscopic removal of ossified posterior longitudinal ligament
      (OPLL) in the thoracic spine: a case report.
AB  - BACKGROUND: When the transthoracic approach is used for the treatment of a
      thoracic ossified posterior longitudinal ligament (OPLL), there could be a lot of
      operative risks, morbidity, and mortality for the patient. CASE REPORT: A 65-year
      old female manifested back pain and tingling sensations in both legs due to OPLL
      at the T6-7 level. A thoracoscopic procedure was performed to remove the OPLL,
      achieving complete decompression of thoracic cord. The symptoms were relieved and
      the patient was discharged on the sixth day after the operation. CONCLUSIONS: A
      minimally invasive procedure using the thoracoscopic technique could be a good
      alternative option in selected cases when a conventional transthoracic approach
      is impossible due to the patient's general condition.

PMID- 20809457
TI  - High-definition imaging in spinal neuroendoscopy.
AB  - BACKGROUND: Spinal endoscopy is still under controversial discussion. An often
      acclaimed critic is the poor endoscopic image quality in comparison with the
      microscope. Since high-definition digital cameras have recently been introduced
      into spinal neuroendoscopy, the aim of the current study is to examine whether
      superior image quality has a relevant impact on intraoperativen orientation.
      MATERIAL AND METHODS: A lumbar endoscopic discectomy was recorded simultaneously
      in High-Definition resolution (HD) and Standard-Definition resolution (SD). 10
      experienced spinal surgeons were asked to identify predefined as well as not
      predefined anatomic structures in HD and SD resolution. Additionally, the video
      quality was rated with grades from 1 ("very good") to 6 ("poor"). RESULTS: Out of
      14 predefined structures an average of 7.8+/-3.3 structures (55.71%) were
      identified in HD, 4.4+/-3.2 structures (31.43%) in SD (p=0.03). Out of 14 not
      predefined anatomical structures, 5.9+/-3.6 were correctly identified in HD,
      2.6+/-2.5 in SD (p=0.05). Misinterpretation of structures occurred in 1.4+/-1
      cases in HD, compared to 3+/-2.2 in SD (p=0.05). Subjective impression of video
      quality was rated 2.2 ("good") for HD, 3.0 ("satisfactory") for SD (p=0.03).
      CONCLUSION: HD in endoscopic discectomy accounts for a significantly more
      reliable identification of anatomic structures in freeze-images in comparison
      with standard definition images. Additionally, the subjective impression of video
      quality is significantly better in HD. This superior identification of structures
      might contribute to improve intraoperative orientation in endoscopic neurosurgery
      using high definition quality technology.

PMID- 20809458
TI  - Percutaneous endoscopic lumbar herniectomy for high-grade down-migrated L4-L5
      disc through an L5-S1 interlaminar approach: a technical note.
AB  - BACKGROUND: L4-L5 disc herniations can be treated with percutaneous endoscopic
      lumbar discectomy (PELD) using a transforaminal posterolateral approach. Although
      PELD has some distinct advantages over conventional open discectomy, inadequate
      decompression is a major cause of failure of the procedure, especially with high
      grade migrations. The objective of this technical note is to present a new
      surgical approach for treating high-grade, down-migrated, L4-L5 disc herniations
      through an L5-S1 interlaminar endoscopic approach. METHOD: This technical report
      presents 4 consecutive patients with high-grade, down-migrated, L4-L5 disc
      herniations, who were treated with PELD through an L5-S1 interlaminar approach
      under local anesthesia and conscious sedation. All patients were evaluated
      clinically using both the visual analogue scale (VAS) for back and leg pain and
      the Oswestry disability index (ODI) and radiologically using MR imaging
      postoperatively. RESULTS: All 4 patients experienced improvement in their
      preoperative symptoms and signs immediately postoperatively. The mean VAS scores
      for back and leg pain improved from 3.75 to 1.75 and from 8.5 to 0.75,
      respectively. The mean ODI score improved from 65% to 3%. Postoperative MR
      imaging also depicted L5 root decompression. There were no complications during
      the procedure. CONCLUSION: This technical note presents a new technique for
      treating high-grade, down-migrated, L4-L5 disc herniations with PELD using an L5
      S1 interlaminar approach.

PMID- 20809459
TI  - Reference levels for serum thyroid function tests of diagnostic and prognostic
      significance.
AB  - A controversy exists on the value of upper thyrotropin (TSH) reference level.
      Currently available studies are based on cross-sectional data leaving uncertainty
      about the prognostic significance of the upper TSH reference level. With the
      present study we sought to establish reference values for serum thyroid function
      tests that are of both diagnostic and prognostic significance. We used data from
      the prospective population-based Study of Health in Pomerania (SHIP) with a 5
      year follow-up (6080 person-years). We included data from 1203 subjects (525
      women) without prevalent subclinical or manifest thyroid disorders. An event-free
      reference population was separated comprising 1053 subjects (473 women). When
      comparing reference values as analyzed from either the whole reference population
      or the event-free reference population, we observed notable differences in TSH
      reference intervals. While the lower TSH reference values were similar in both
      populations, the upper value was 1.95 mIU/l and thus by 7.6% lower in subjects
      without incident events compared to the whole reference population. Both
      populations did not substantially differ with respect to serum FT3 and FT4
      reference intervals. The upper TSH reference value is lower than recommended when
      both diagnostic and prognostic significance are considered in the definition of
      the TSH reference range.

PMID- 20809460
TI  - [For a structural classification of the German prenatal and maternity care].

PMID- 20809461
TI  - [Basic epidemiological characteristics of influenza infection].
AB  - Influenza is a relatively serious infection that affects hundreds of thousands of
      people every year in the Czech Republic alone, with unnecessary deaths as a
      possible outcome. Vaccination against influenza is the most important preventive
      measure. The highest incidence of seasonal influenza is reported in school-age
      children and young adults while the highest mortality is observed among the
      elderly. Pandemic influenza may significantly differ from seasonal influenza in
      these two aspects. Other epidemiological characteristics of seasonal influenza
      are presented and compared with those of 2009 pandemic A/H1N1 ("Mexican")
      influenza that caused the first pandemic of the 21st century.

PMID- 20809462
TI  - [Viral hepatitis in immunosuppressed patients].
AB  - In patients with chronic HBV infection, immunosuppressive therapy leads to the
      loss of immune control of replication and excessive increase of HBV viremia.
      Reactivation of HBV is usually characterized by ALT activity elevation but it may
      also cause acute liver failure. In patients with a past history of HBV infection
      (anti-HBc positive), the virus persists in liver cells and may lead to HBV
      recurrence with identical manifestation. Reactivation and recurrence of hepatitis
      B may be induced not only by immunosuppressive therapy, but also by anti-CD20 or
      anti-TNFa treatment. In inactive HBsAg carriers, HBV recurrence and reactivation
      may be prevented by prophylactic antiviral therapy with lamivudine or other
      synthetic antivirals (tenofovir, entecavir). Patients who underwent HBV infection
      in the past should be closely monitored and the treatment should be started when
      viremia increases. In chronic HCV infection, viremia also increases due to
      immunosuppression, progression of liver fibrosis is accelerated, but fulminant
      liver failure is rare. In HCV infected patients, preemptive antiviral treatment
      cannot be used. In immunocompromised patients, therapy with peginterferon alpha
      should be indicated individually. Kidney transplant candidates should undergo
      antiviral treatment before kidney transplantation, during the hemodialysis
      period.

PMID- 20809463
TI  - [Human metapneumovirus].
AB  - Respiratory viral infections are the most significant cause of increased
      mortality and morbidity especially in immunocompromised people. These infections
      are increasingly recognized as being the cause of the failure of a graft or the
      cause of death in both solid organ and hematopoietic stem cell transplant
      recipients. Treatment with potent immunosuppressive medication is necessary for
      regulation in order to prevent rejection of solid organs and graft-versus-host
      disease. As a consequence of this therapy, infections are more common.
      Respiratory viral infections are the most frequent and serious complications
      after hematopoietic stem cell transplantation (HSCT). Despite increased methods
      of testing for viral pathogens, nearly 10% of pneumonia in HSCT recipients still
      remain "idiopathic pneumonia syndrome". Recently described human metapneumovirus
      could be one of the etiological agents of this syndrome.

PMID- 20809464
TI  - [Options for the detection and identifications of agents causing viral
      hemorrhagic fevers].
AB  - Viral hemorrhagic fevers (VHFs) belong to the most deadly diseases. Therefore
      rapid detection and identification of causal agent is very important for
      epidemiological investigation and countermeasures. The review present all
      published information about VHF detection and identification, with focus on
      polymerase chain reaction (PCR) methods. In the first part, basic information
      about microbiological diagnostic technique is provided. The second part is
      concerned with detection and identification methods for individual agents
      causingt VHFs.

PMID- 20809465
TI  - [Experiences with the treatment of chronic hepatitis C and prognostic factors for
      its efficacy in clinical practice].
AB  - OBJECTIVE: The study aimed at evaluating antiviral therapy and the impact of
      selected factors on its efficacy in patients with chronic hepatitis C treated at
      the Department of Infectology and Travel Medicine in Kosice, Slovakia, between
      2003 and 2007. MATERIAL AND METHODS: A retrospective analysis of a group of 213
      patients treated for chronic hepatitis C and of prognostic factors for treatment
      efficacy in a subgroup of 159 patients who completed therapy with pegylated
      interferon alpha and ribavirin. RESULTS: From the entire group, 193 patients were
      treated with a combination of pegylated interferon and ribavirin, 5 received
      pegylated interferon monotherapy and in 15 cases, conventional interferon was
      used. A total of 179 patients (84 %) were treated for the first time, the
      remaining 34 patients were treated repeatedly. Genotype 1 was detected in 91.5 %
      of 189 studied patients. Liver biopsy was performed in 143 patients, with mild,
      moderate and severe histological changes or liver cirrhosis being detected in
      46.9 %, 38.5 % and 14.7 % of them, respectively. In 12.2 % of cases, treatment
      was discontinued due to adverse effects. In the group of 159 patients who
      completed therapy, sustained viral response (SVR) was found in 35.8 %; another
      12.6 % had viral response at the end of therapy (SVR has not been assessed as
      yet). Viral relapse or breakthrough were observed in 26.4 % and 25.2 % showed no
      response. Patients who achieved SVR were more frequently infected with genotypes
      2 and 3, had lower degrees of liver fibrosis, lower mean age and more frequently
      achieved complete early viral response. By contrast, the group of non-responders
      was characterized by a higher proportion of patients with reduced therapy below
      80 %. The other observed differences such as male/female ratio, weight,
      proportion of patients with normal ALT activity or proportion of previously
      untreated patients were not significant. CONCLUSION: The efficacy of treatment in
      our group adjusted for the adverse proportion of genotypes and proportion of
      patients with repeated therapy was comparable with the literature data. The
      favorable prognostic factors observed in the group included infection with
      genotypes 2 or 3, lower degree of liver fibrosis and lower age.

PMID- 20809466
TI  - [Hepatitis B immunization of patients with inherited bleeding disorders: personal
      experiences].
AB  - Hepatitis B immunization of patients with inherited bleeding disorders: personal
      experiences Hepatitis B vaccination was initiated in 55 patients with inherited
      bleeding disorders in 1994-2009. Patients received three doses of subcutaneous
      recombinant vaccine containing 20 mg HBsAg (hepatitis B surface antigen) at 0, 1
      and 6 months. Blood samples were obtained at the starting of vaccination, 1-3
      months after immunization, and biennially thereafter. The samples were tested for
      HBsAg, hepatitis B surface and core antibodies (anti-HBs, anti-HBc). Protective
      anti-HBs level (>=10 IU/l) after immunization was proved in 50 of 51 patients (98
      %). Waning of protective anti-HBs antibodies was detected in 4 % and 24 % of
      patients within 5 and 10 years after vaccination. No HBsAg carrier status or anti
      HBc seroconversion were detected. Subcutaneous vaccination against hepatitis B
      provides long-term protection in patients with inherited bleeding disorders.

PMID- 20809467
TI  - [Family in retreat].

PMID- 20809468
TI  - [Diagnosis and classification of personality disorders in adolescence - how can
      current research findings contribute to an understanding of this construct?].
AB  - OBJECTIVE: The diagnosis and classification of personality disorders in
      adolescence remains a controversially discussed topic. METHOD: This review
      reports recent research findings on the comorbidity and the diagnosis of
      personality disorders in adolescence and on their neurobiological and
      neuropsychological correlates. RESULTS: On the one hand, the latest research
      findings refer to the implication that personality disorders in adolescence can
      be reliably diagnosed with the existing instruments used in the diagnosis of
      adults. On the other hand, researchers criticize the lack of a youth-specific
      concept of assessment, which could be used as a common foundation to study this
      clinically so relevant disorder. CONCLUSIONS: Diagnostic as well as longitudinal
      studies within the scope of networks are required in order to differentiate
      personality disorders in adolescence from other youth-related disorders.

PMID- 20809469
TI  - [Concepts of therapy for children with dyslexia].
AB  - Numerous methods based on very different concepts are available to treat children
      with dyslexia. Basically, symptomatic and causal principles can be distinguished.
      Among the symptomatic methods are systematic programmes based on learning theory,
      in which reading and spelling or precursors of these abilities are directly
      trained. Causal methods promise pronounced and persistent improvement of reading
      and spelling abilities through elimination of the postulated reason underlying
      the learning disabilities. Among the causal methods are treatment programmes that
      train low-level functions. Such training is based on the assumption that deficits
      of auditory, visual or kinesthetic perception, of motor skills or of the
      coordination of cerebral functional areas are at the bottom of specific learning
      disabilities. Concepts of other causal methods act on the assumption that
      learning processes are blocked or that abnormal medical conditions or psychiatric
      disorders constitute the background of dyslexia. Reviewed in the article are
      treatment concepts for children with dyslexia in the German-speaking countries
      and the methods of treatment derived from the different concepts. Results of
      evaluation studies are summarized and characteristics of effective treatment
      methods are listed. It is stressed that efficacy is proven only for symptomatic
      training programmes but not for causal methods.

PMID- 20809470
TI  - [Personality disorders in adolescent patients with anorexia and bulimia nervosa].
AB  - OBJECTIVE: The present study aimed to ascertain the occurrence of personality
      disorders (PD) in adolescent patients with anorexia (AN) and bulimia nervosa (BN)
      by means of the Structured Clinical Interview for DSM-IV Personality Disorders
      (SCID-II). METHOD: 99 female adolescent patients (57 AN - restrictive type, 17 AN
      - binge-purging type, 25 BN; M(age) = 16.3 +/- 1.6) were consecutively assessed
      by means of SCID-II. Furthermore, the influence of age, axis-I-comorbidities, and
      type of treatment according to PD were examined. RESULTS: 30.3% of the patients
      met the criteria for PD according to SCID-II. AN patients of the binge-purging
      type showed higher prevalences of PD and higher dimensional scores than the other
      eating disorder groups. Moreover, our findings indicate that age and axis-I
      comorbidities are associated with the development of PD. CONCLUSION: Significant
      differences in the occurrence of PD in the three eating disorder groups were
      found. Patients of the AN binge-purging type are more often affected than
      restricting AN or BN patients are. This, and also the influence of age and axis-I
      comorbidities, should be taken into account in the treatment of patients with
      eating disorders.

PMID- 20809471
TI  - [Conditions for success in a lifestyle intervention weight-reduction programme
      for overweight or obese children and adolescents].
AB  - OBJECTIVE: To analyze whether caregiver and family characteristics predict
      success in a family-based lifestyle intervention programme for overweight or
      obese children and adolescents. METHOD: Participants were 136 overweight or obese
      children and adolescents (7-15 years) who attended a family-based weight
      reduction programme. BMI and BMI standard deviation scores (BMI-SDS) of the index
      child, BMI of family members, family adversity characteristics, and depression
      and attachment attitudes of the primary caregiver were assessed. 116 participants
      finished the 12-month programme: 100 (85.3%) showed a decrease of the BMI-SDS, 79
      (68.1%) a more than 5% reduction of the BMI-SDS. These "successful" children were
      compared to 56 "unsuccessful" ones (dropouts and children with a BMI-SDS
      reduction of 5% or less). RESULTS: Failure to reduce weight considerably (<= 5%
      reduction of BMI-SDS, or dropout) occurred more frequently in older children and
      in cases with obese sibling(s), maternal depression, and maternal avoidant
      attachment attitude. In a logistic regression analysis, maternal depression as
      well as attachment attitude, and the age of the index child explained common
      variance, while the presence of obese sibling(s) explained unique variance in non
      responding. CONCLUSION: Our data suggest that special support should be provided
      to adolescents with obese sibling(s) and to adolescents with mothers suffering
      from depression and exhibiting an avoidant attachment style, so as to meet the
      specific needs of all participating families and to prevent the discouraging
      experience of failure in weight-control interventions. The efficacy of these
      modules must be tested in further studies.

PMID- 20809472
TI  - [Evaluation of a two-year intensive outpatient care programme for adolescents
      with schizophrenia].
AB  - OBJECTIVE: The Trialog project offers patients with early-onset schizophrenia
      (EOS) a two-year programme of residential outpatient care following discharge
      from a clinic. The programme aims to support their further recovery and
      independence and encompasses interactive and psycho-educational multifamily care,
      coping with persistent symptoms, development of socio-emotional competence,
      independent house keeping, and support of school and vocational training.
      METHODS: To evaluate psychopathology along with social and neuropsychological
      function for 12 participants over a period of 2 years. Their progress was
      compared with that of 12 EOS patients who did not attend Trialog following
      discharge. RESULTS: Participants showed a significantly greater decrease of
      positive and negative symptoms, as opposed to an increase in positive symptoms in
      the comparison group. Measures of social function, neuropsychological indicators
      of memory, (selective) attention, and psychomotor speed improved more than in the
      comparison subjects. Neither group showed changes in measures of intelligence or
      in the subjective quality of life. CONCLUSIONS: First analyses raise hope that
      monitoring participant performance in the programme of the "Trialog project" will
      improve the treatment and care of EOS-patients in the critical first years
      following the onset of schizophrenia.

PMID- 20809476
TI  - Effect of fluvastatin, lovastatin, nifedipine and verapamil on the systemic
      exposure of nateglinide in rabbits.
AB  - A diabetic patient may suffer simultaneously from cardiovascular disease; thus,
      lipid-lowering or anti-hypertensive agents could be given together with
      nateglinide. The pharmacokinetics of nateglinide were investigated in the
      presence and absence of HMG-CoA reductase inhibitors (fluvastatin, lovastatin)
      and calcium channel blockers (verapamil, nifedipine) in rabbits. A
      pharmacokinetic modeling approach was used to quantify the effects of the drugs
      that significantly influenced the pharmacokinetics of nateglinide. Fluvastatin
      and nifedipine shifted the time course of serum nateglinide concentrations
      upwards; there was no significant change with verapamil or lovastatin. The C(max)
      and AUC(inf) increased 1.5- (p<0.05) and 1.3-fold in the presence of fluvastatin
      and 1.8- (p<0.01) and 2.4-fold (p<0.01) in the presence of nifedipine,
      respectively. In a simultaneous nonlinear regression, fluvastatin and nifedipine
      decreased the elimination rate constant, by 76% and 32%, respectively.
      Fluvastatin and nifedipine increased the systemic exposure of nateglinide in
      rabbits, probably due to their inhibitory action on the metabolism of nateglinide
      by CYP2C5 (human CYP2C9). The concomitant use of fluvastatin and/or nifedipine
      with nateglinide is quite likely; therefore, the clinical consequences of long
      term treatments must be considered.

PMID- 20809477
TI  - Secondary hemophagocytic syndrome in adults: a case series of 18 patients in a
      single institution and a review of literature.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is rare in adults and is usually fatal
      without treatment. We present a consecutive series of 18 adults with HLH
      diagnosed at our institution between 2004 and 2009. All diagnoses were confirmed
      by pathology. The median age at diagnosis was 56 years (range: 18-73 years), with
      a male: female ratio of 2:1. Patients uniformly presented with fever. Fifty-five
      per cent of the patients presented with evidence of hepatomegaly or splenomegaly.
      All of the patients had at least a bi- or trilineage cytopenia. Elevated liver
      enzymes, hyperferritinemia, hypertriglyceridemia and hyperfibrinogenemia were
      seen in 50, 100, 40 and 50% of patients, respectively. The presumed causes were
      as follows; haematological malignancies (n = 4), post-autologous stem cell
      transplant (n = 2), infection (n = 2), rheumatologic illness (n = 2), sickle cell
      disease (n = 1), post-orthotopic liver transplant (n = 1) and idiopathic (n = 3).
      The median time from suspicion to diagnosis was 5 days (1-27 days).
      Corticosteroids and/or cyclosporine were the most frequently used treatment
      regimen. Other agents used were etoposide, IVIG, cyclophosphamide and
      chemotherapy. The mortality rate was 72%, with multi-system organ failure being
      the most common cause of death. Median survival time from diagnosis was 35 days.
      Six patients are alive to date. In a univariate analysis, the presence of fever
      was the only factor that was statistically significant for predicting a poor
      prognosis (early mortality) (p = 0.05). In conclusion, a high index of suspicion
      is the critical factor for early diagnosis. Early treatment with
      immunosuppressant is warranted, and a thorough diagnostic evaluation to identify
      the underlying cause should be undertaken.

PMID- 20809478
TI  - Bayesian latent variable modelling in studies of air pollution and health.
AB  - This paper describes the use of Bayesian latent variable models in the context of
      studies investigating the short-term effects of air pollution on health.
      Traditional Poisson or quasi-likelihood regression models used in this area
      assume that consecutive outcomes are independent (although the latter allows for
      overdispersion), which in many studies may be an untenable assumption as temporal
      correlation is to be expected. We compare this traditional approach with two
      Bayesian latent process models, which acknowledge the possibility of short-term
      autocorrelation. These include an autoregressive model that has previously been
      used in air pollution studies and an alternative based on a moving average
      structure that we describe here. A simulation study assesses the performance of
      these models when there are different forms of autocorrelation in the data.
      Although estimated risks are largely unbiased, the results show that assuming
      independence can produce confidence intervals that are too narrow. Failing to
      account for the additional uncertainty which may be associated with (positive)
      correlation can result in confidence/credible intervals being too narrow and thus
      lead to incorrect conclusions being made about the significance of estimated
      risks. The methods are illustrated within a case study of the effects of short
      term exposure to air pollution on respiratory mortality in the elderly in London,
      between 1997 and 2003.

PMID- 20809479
TI  - AAV plasmid DNA simplifies liver-directed in vivo gene therapy: comparison of
      expression levels after plasmid DNA-, adeno-associated virus- and adenovirus
      mediated liver transfection.
AB  - BACKGROUND: Successful liver gene therapy depends on efficient gene transfer
      techniques and long-lasting gene expression after successful transfer. Over the
      last decades, important progress has been made with the introduction of viral
      vectors using animal models, although their use is hampered by a complex and
      costly preparation compared to the simple and cost-effective preparation of
      plasmid DNA. These problems become even more critical when considering the
      application of viral vectors in human gene therapy and gene therapy trials. In a
      previous study, we were able to show that the hydrodynamics-based gene transfer
      of plasmid-DNA, containing the adeno-associated-virus specific inverted terminal
      repeats (AAV-ITR), prolongs gene expression in the liver, although it remained
      unclear whether plasmid gene transfer could achieve similar expression levels
      compared to viral-vector gene transfer. METHODS: Rat livers were transfected in
      vivo with AAV-ITR-containing plasmid-DNA using a modified hydrodynamics-based
      procedure. Expression levels were monitored thereafter and compared with
      expression levels after viral-vector gene transfer. RESULTS: A high and stable
      long-term expression was achieved after in vivo transfection of rat livers with
      AAV-ITR-containing plasmids. The expression course resembled that after AAV
      mediated gene transfer, and the expression was at least as high, and lasted as
      long, compared to recombinant AAV-mediated gene transfer. CONCLUSIONS: We
      consider AAV-ITR-containing plasmids as a simple and cost-effective alternative
      to recombinant viral vectors, especially for liver-directed gene therapy in
      rodents. With ongoing progress in gene transfer methods for naked DNA, these
      plasmids may also become a successful alternative to recombinant viral vectors in
      human gene therapy.

PMID- 20809480
TI  - The effect of salvage therapy on survival in a longitudinal study with treatment
      by indication.
AB  - We consider using observational data to estimate the effect of a treatment on
      disease recurrence, when the decision to initiate treatment is based on
      longitudinal factors associated with the risk of recurrence. The effect of
      salvage androgen deprivation therapy (SADT) on the risk of recurrence of prostate
      cancer is inadequately described by the existing literature. Furthermore,
      standard Cox regression yields biased estimates of the effect of SADT, since it
      is necessary to adjust for prostate-specific antigen (PSA), which is a time
      dependent confounder and an intermediate variable. In this paper, we describe and
      compare two methods which appropriately adjust for PSA in estimating the effect
      of SADT. The first method is a two-stage method which jointly estimates the
      effect of SADT and the hazard of recurrence in the absence of treatment by SADT.
      In the first stage, PSA is predicted in the absence of SADT, and in the second
      stage, a time-dependent Cox model is used to estimate the benefit of SADT,
      adjusting for PSA. The second method, called sequential stratification,
      reorganizes the data to resemble a sequence of experiments in which treatment is
      conditionally randomized given the time-dependent covariates. Strata are formed,
      each consisting of a patient undergoing SADT and a set of appropriately matched
      controls, and analysis proceeds via stratified Cox regression. Both methods are
      applied to data from patients initially treated with radiation therapy for
      prostate cancer and give similar SADT effect estimates.

PMID- 20809481
TI  - Random-effects meta-regression models for studying nonlinear dose-response
      relationship, with an application to alcohol and esophageal squamous cell
      carcinoma.
AB  - A fundamental challenge in meta-analyses of published epidemiological dose
      response data is the estimate of the function describing how the risk of disease
      varies across different levels of a given exposure. Issues in trend estimate
      include within studies variability, between studies heterogeneity, and nonlinear
      trend components. We present a method, based on a two-step process, that
      addresses simultaneously these issues. First, two-term fractional polynomial
      models are fitted within each study included in the meta-analysis, taking into
      account the correlation between the reported estimates for different exposure
      levels. Second, the pooled dose-response relationship is estimated considering
      the between studies heterogeneity, using a bivariate random-effects model. This
      method is illustrated by a meta-analysis aimed to estimate the shape of the dose
      response curve between alcohol consumption and esophageal squamous cell carcinoma
      (SCC). Overall, 14 case-control studies and one cohort study, including 3000
      cases of esophageal SCC, were included. The meta-analysis provided evidence that
      ethanol intake was related to esophageal SCC risk in a nonlinear fashion. High
      levels of alcohol consumption resulted in a substantial risk of esophageal SCC as
      compared to nondrinkers. However, a statistically significant excess risk for
      moderate and intermediate doses of alcohol was also observed, with no evidence of
      a threshold effect.

PMID- 20809482
TI  - Bio-creep in non-inferiority clinical trials.
AB  - After a non-inferiority clinical trial, a new therapy may be accepted as
      effective, even if its treatment effect is slightly smaller than the current
      standard. It is therefore possible that, after a series of trials where the new
      therapy is slightly worse than the preceding drugs, an ineffective or harmful
      therapy might be incorrectly declared efficacious; this is known as 'bio-creep'.
      Several factors may influence the rate at which bio-creep occurs, including the
      distribution of the effects of the new agents being tested and how that changes
      over time, the choice of active comparator, the method used to account for the
      variability of the estimate of the effect of the active comparator, and changes
      in the effect of the active comparator from one trial to the next (violations of
      the constancy assumption). We performed a simulation study to examine which of
      these factors might lead to bio-creep and found that bio-creep was rare, except
      when the constancy assumption was violated.

PMID- 20809483
TI  - Semi-parametric latent process model for longitudinal ordinal data: Application
      to cognitive decline.
AB  - Ordinal and quantitative discrete data are frequent in biomedical and
      neuropsychological studies. We propose a semi-parametric model for the analysis
      of the change over time of such data in longitudinal studies. A threshold model
      is defined where the outcome value depends on the current value of an underlying
      Gaussian latent process. The latent process model is a Gaussian linear mixed
      model with a non-parametric function of time, f(t), to model the expected change
      over time. This model includes random-effects and a stochastic error process to
      flexibly handle correlation between repeated measures. The function f(t) and all
      the model parameters are estimated by penalized likelihood using a cubic-spline
      approximation for f(t). The smoothing parameter is estimated by an approximate
      cross-validation criterion. Confidence bands may be computed for the estimated
      curves for the latent process and, using a Monte Carlo approach, for the outcome
      in its natural scale. The method is applied to the Paquid cohort data to compare
      the time-course over 14 years of two cognitive scores in a sample of 350 future
      Alzheimer patients and in a matched sample of healthy subjects.

PMID- 20809484
TI  - Generating stable Chinese hamster ovary cell clones to produce a truncated SARS
      CoV spike protein for vaccine development.
AB  - The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS
      CoV) is important for vaccine development. S(TR2) (an 88 kDa truncated SARS-CoV
      TW1 S protein carrying the S fragments S-74-253, S-294-739, and S-1129-1255) is
      capable of expressing a major form of glycoprotein as endo H-sensitive (~115 kDa)
      in CHO cells. To establish stable expressing cell clones, we transfected CHO/dhFr
      cells with the amplifiable vectors ISID (IRES-driven dhfr) and ISIZ (SV40-driven
      dhfr) to select stepwise MTX, and observed enhanced ~115 kDa glycoform generation
      through gene amplification. Following stepwise MTX selection, we compared gene
      amplification levels between two vectors in engineered CHO cell chromosomes.
      These results confirm that the IRES-driven dhfr promoter generates greater gene
      amplification, which in turn enhances S(TR2) expression. Our results indicate
      that the ~115 kDa glycoform of S(TR2) protein was capable of increasing after
      gene amplification. The S(TR2) glycoform did not change between suspension and
      serum-free cultures, suggesting that the stable and amplified cell clones
      analyzed in this study have potential for producing homologous S(TR2) on a large
      scale.

PMID- 20809485
TI  - Accuracy and cut-off point selection in three-class classification problems using
      a generalization of the Youden index.
AB  - We study properties of the index J(3), defined as the accuracy, or the maximum
      correct classification, for a given three-class classification problem.
      Specifically, using J(3) one can assess the discrimination between the three
      distributions and obtain an optimal pair of cut-off points c(1)<c(2) in the sense
      that the sum of the correct classification proportions will be maximized. It also
      serves as the generalization of the Youden index in three-class problems.
      Parametric and non-parametric approaches for estimation and testing are
      considered and methods are applied to data from an MRS study on human
      immunodeficiency virus (HIV) patients.

PMID- 20809486
TI  - Empirical constrained Bayes predictors accounting for non-detects among repeated
      measures.
AB  - When the prediction of subject-specific random effects is of interest,
      constrained Bayes predictors (CB) have been shown to reduce the shrinkage of the
      widely accepted Bayes predictor while still maintaining desirable properties,
      such as optimizing mean-square error subsequent to matching the first two moments
      of the random effects of interest. However, occupational exposure and other
      epidemiologic (e.g. HIV) studies often present a further challenge because data
      may fall below the measuring instrument's limit of detection. Although
      methodology exists in the literature to compute Bayes estimates in the presence
      of non-detects (Bayes(ND)), CB methodology has not been proposed in this setting.
      By combining methodologies for computing CBs and Bayes(ND), we introduce two
      novel CBs that accommodate an arbitrary number of observable and non-detectable
      measurements per subject. Based on application to real data sets (e.g.
      occupational exposure, HIV RNA) and simulation studies, these CB predictors are
      markedly superior to the Bayes predictor and to alternative predictors computed
      using ad hoc methods in terms of meeting the goal of matching the first two
      moments of the true random effects distribution.

PMID- 20809487
TI  - Mood and Anxiety Symptom Questionnaire anxiety items in an adult british clinical
      sample: one scale or two?
AB  - In seeking to establish British clinical normative data for the two anxiety
      scales (anxious symptoms and anxious arousal) of the Mood and Anxiety Symptom
      Questionnaire (MASQ), the responses of 237 British National Health Service
      outpatients were examined. Factor analyses (exploratory and confirmatory) failed
      to confirm the expected structure. Data were presented and discussed, considering
      the 28 anxiety item pool in terms of being either two highly correlated scales of
      somatic anxiety versus psychological anxiety, or as a single general anxiety
      scale. As neither of these outcomes accorded with the test constructors'
      assumptions, it was concluded that the MASQ is not a suitable measure for
      assessing the tripartite model of adverse mood states in British clinical
      samples.

PMID- 20809489
TI  - From bench to patients: we really can move mountains.

PMID- 20809491
TI  - IL-22-producing CD4+ T cells: middle-men between the immune system and its
      environment.
AB  - CD4(+) Th cell populations such as Th1, Th2, Th17 and regulatory T cells regulate
      immune responses by inducing (or inhibiting) proliferation, differentiation and
      activation of other immune cells. Recent findings have expanded the universe of
      CD4(+) T-cell subsets by identifying a cell population dedicated to the
      production of the cytokine IL-22. These so-called Th22 cells may mediate
      interactions of the immune system with stromal cells. Th22 cells have so far only
      been observed in humans and are present in inflamed tissues in some skin diseases
      and evidence suggests that these cells may play a role in the disease process. It
      is therefore of importance to learn the mechanisms of regulation of development
      and function of these cells. A paper in the current issue of the European Journal
      of Immunology indicates that the ligand-dependent transcription factor aryl
      hydrocarbon receptor is important for regulating IL-22 production of this new
      class of human Th cells.

PMID- 20809497
TI  - An altar in honor of the anatomical gift.
AB  - On All Saints Day 2009 a monument for body donors was unveiled by the Department
      of Anatomy, at the Radboud University Nijmegen Medical Centre (RUNMC). Although
      body donation to medical science contributes substantially to the quality of
      medical education, the ceremony was only the first time that the RUNMC publicly
      reciprocated the anatomical gift. By means of the monument the department of
      Anatomy endeavors to express gratitude for the gift of body donors and raise
      awareness among students to value the gift and treat donor bodies with the proper
      respect. Furthermore, the large attendance of bereaved at the unveiling ceremony,
      revealed another equally important meaning of the monument, which is the
      significance of the monument to the donor kin. The wish of a body donor has large
      implications for the way bereaved can take leave of the donor; there is limited
      time to bade the deceased farewell, the body will not be available for a funeral,
      and the donor kin stay behind empty handed without even a grave or ashes.
      Therefore the monument can be meaningful by facilitating the bereaved with a
      place of commemoration. The design of the monument anticipates on these multiple
      meanings and symbolisms by placing an old marble dissection table in the shape of
      an altar and fixing a bronze sculpture of a phoenix as symbol of
      imperishableness.

PMID- 20809492
TI  - Directing traffic on the NKT-cell highway: a key role for ThPOK.
AB  - CD1d-restricted NKT cells include CD4(+) and DN subsets, with an additional
      CD8(+) subset that is present in humans but not in mice. The molecular regulation
      of CD4/CD8 expression by NKT cells, and differentiation of these NKT-cell
      subsets, is poorly understood. The transcription factors GATA3 and ThPOK regulate
      lineage commitment of conventional MHC class II-restricted CD4(+) T cells;
      however, their role in CD4/CD8 expression by CD1d-restricted NKT cells is less
      clear. A new study in this issue of the European Journal of Immunology
      demonstrates a key role for ThPOK in differentiation of NKT-cell subsets. This
      study reveals that GATA3 and ThPOK are necessary for the development of CD4(+)
      NKT cells. Furthermore, ThPOK-deficient mice generate an unusual population of
      CD8(+) NKT cells, which are absent in control mice. This study sheds new light on
      the underlying molecular events leading to the emergence of distinct NKT-cell
      subsets.

PMID- 20809498
TI  - Teaching skills to promote clinical reasoning in early basic science courses.
AB  - Basic and superior reasoning skills are woven into the clinical reasoning process
      just as they are used to solve any problem. As clinical reasoning is the central
      competence of medical education, development of these reasoning skills should
      occur throughout the undergraduate medical curriculum. The authors describe here
      a method of teaching reasoning skills in a clinical context during a human
      anatomy course.

PMID- 20809502
TI  - Flow cytometric analysis of CD123 is useful for immunophenotyping classical
      Hodgkin lymphoma.
AB  - Although the diagnosis of classical Hodgkin lymphoma (CHL) is traditionally made
      morphologically in tissue sections, it is now possible to diagnose CHL by flow
      cytometry (FC). In an effort to identify additional antigens on Hodgkin and Reed
      Sternberg (HRS) cells that might be useful for immunophenotyping this lymphoma by
      FC, we examined the expression of CD123 (alpha chain of the IL-3R) on HRS cells
      and compared this with the expression of CD123 in other lymph node samples (372
      tissue specimens, including 98 reactive and 274 neoplastic cases), using a nine
      color FC reagent combination including anti-CD123. CD123 was found to be
      expressed on the majority of HRS cell populations (59% of 59 CHL lymph nodes
      examined), rarely on B-cell non-Hodgkin lymphomas (NHLs) (3 of 3 hairy cell
      leukemia cases, 3 of 29 chronic lymphocytic leukemia/small lymphocytic lymphoma
      (CLL/SLL) cases, 1 of 55 large B-cell lymphoma cases, but not on 95 other B-cell
      NHL examined), and in none of the 16 T-cell NHL cases examined. In reactive lymph
      nodes, CD123 expression was largely limited to plasmacytoid dendritic cells and
      rare histiocyte populations that can readily be distinguished from HRS
      populations. As the expression of this antigen is shown to be relatively limited
      in B- and T-NHL and in reactive lymph node populations, assessment of CD123
      expression is useful for supporting the FC diagnosis of CHL.

PMID- 20809501
TI  - Aberrant expression of c-met and HGF/c-met pathway provides survival advantage in
      B-chronic lymphocytic leukemia.
AB  - BACKGROUND: B-chronic lymphocytic leukemia (B-CLL) is characterized by
      accumulation of CD5(+) B lymphocytes. Decreased VLA-4 (Cd49d/CD29) and CD11a
      expression and defective adhesion in B-CLL have been previously shown, although
      there was no substantial data about its importance in immunobiology of B-CLL. The
      hepatocyte growth factor (HGF) receptor, c-met, plays a role in adhesion by
      acting on VLA-4. c-met and VLA-4 share crucial signaling molecules in cell
      survival. In this study, relationship between expressions of c-met and CD49d,
      CD11a, and additional common signaling molecules in B-CLL was investigated.
      METHODS: White blood cells from 24 patients with CLL were studied by flow
      cytometry and/or western blotting prior to and after culturing with recombinant
      HGF. HGF level from sera was measured with a bead-based flow cytometric assay.
      RESULTS: c-metalpha and c-metbeta were expressed on B-CLL cells, while no
      expression was observed on normal donor CD19+ cells. This increase was inversely
      correlated with decreased expression of adhesion molecules. Serum level of HGF in
      B-CLL was found to be increased. In vitro experiments showed that HGF supported
      survival in B-CLL cells supporting the possible function of HGF/c-met pathway in
      B-CLL. Furthermore, expressions of critical signaling molecules shared by both
      VLA-4 and HGF/c-met systems including Bcl-XL, Akt, PI3K, and phospho-bad(136)
      following HGF stimulations of B-CLL cells have been found to be increased.
      CONCLUSION: Increased expression of c-met and HGF may bypass the importance of
      expression of critical adhesion molecules and support survival of B-CLL cells. c
      met, being one of the surface tyrosine kinases, may serve as a target for future
      therapies in B-CLL meriting more attention.

PMID- 20809503
TI  - In vitro study of the effects of ELF electric fields on gene expression in human
      epidermal cells.
AB  - An acceleration of differentiation, at the expense of proliferation, is observed
      after exposure of various biological models to low frequency and low amplitude
      electric and electromagnetic fields. Following these results showing significant
      modifications, we try to identify the biological mechanism involved at the cell
      level through microarray screening. For this study, we use epidermis cultures
      harvested from human abdominoplasty. Two platinum electrodes are used to apply
      the electric signal. The gene expressions of 38,500 well-characterized human
      genes are analyzed using Affymetrix((r)) microarray U133 Plus 2.0 chips. The
      protocol is repeated on three different patients. After three periods of
      exposure, a total of 24 chips have been processed. After the application of ELF
      electric fields, the microarray analysis confirms a modification of the gene
      expression of epidermis cells. Particularly, four up-regulated genes (DKK1,
      TXNRD1, ATF3, and MME) and one down-regulated gene (MACF1) are involved in the
      regulation of proliferation and differentiation. Expression of these five genes
      was also confirmed by real-time rtPCR in all samples used for microarray
      analysis. These results corroborate an acceleration of cell differentiation at
      the expense of cell proliferation.

PMID- 20809504
TI  - Extremely low-frequency electromagnetic fields affect the immune response of
      monocyte-derived macrophages to pathogens.
AB  - This study aimed to determine the effect of extremely low-frequency
      electromagnetic fields (ELF-EMF) on the physiological response of phagocytes to
      an infectious agent. THP-1 cells (human monocytic leukemia cell line) were
      cultured and 50 Hz, 1 mT EMF was applied for 4-6 h to cells induced with
      Staphylococcus aureus or interferon gamma/lipopolysaccharide (IFgamma/LPS).
      Alterations in nitric oxide (NO), inducible nitric oxide synthase (iNOS) levels,
      heat shock protein 70 levels (hsp70), cGMP levels, caspase-9 activation, and the
      growth rate of S. aureus were determined. The growth curve of exposed bacteria
      was lower than the control. Field application increased NO levels. The increase
      was more prominent for S. aureus-induced cells and appeared earlier than the
      increase in cells without field application. However, a slight decrease was
      observed in iNOS levels. Increased cGMP levels in response to field application
      were closely correlated with increased NO levels. ELF-EMF alone caused increased
      hsp70 levels in a time-dependent manner. When cells were induced with S. aureus
      or IFgamma/LPS, field application produced higher levels of hsp70. ELF-EMF
      suppressed caspase-9 activation by a small extent. These data confirm that ELF
      EMF affects bacterial growth and the response of the immune system to bacterial
      challenges, suggesting that ELF-EMF could be exploited for beneficial uses.

PMID- 20809507
TI  - DNA-DNA sequence homology recognition: physical mechanisms and open questions.
AB  - First, we summarize recent experimental facts on homologous DNA pairing in vitro
      and discuss possible mechanisms of DNA-DNA sequence recognition. Then, we
      overview the mechanism of DNA-DNA recognition based on complementarity of DNA
      charge patterns. The theory predicts the recognition energy up to 10 k(B) T for
      close parallel homologous DNA fragments of gene-relevant lengths. We argue why
      this estimate cannot be directly applied to pairing of homologous DNA loci in
      experiments on yeast chromosomes. Namely, DNA-DNA distances assessed from
      experiments are much larger than those typically used in theory. Finally, we
      suggest some experiments that could help to judge whether short-range
      electrostatic forces indeed govern DNA pairing. This viewpoint paper introduces
      recently developed theoretical concepts to molecular biologists, with a hope to
      generate a junction between theory and future experiments on DNA recognition.

PMID- 20809509
TI  - LB1 from Liang Bua, Flores: craniofacial asymmetry confirmed, plagiocephaly
      diagnosis dubious.

PMID- 20809510
TI  - Molecular characterization of organic electronic films.
AB  - Organic electronics have emerged as a viable competitor to amorphous silicon for
      the active layer in low-cost electronics. The critical performance of organic
      electronic materials is closely related to their morphology and molecular
      packing. Unlike their inorganic counterparts, polymers combine complex repeat
      unit structure and crystalline disorder. This combination prevents any single
      technique from being able to uniquely solve the packing arrangement of the
      molecules. Here, a general methodology for combining multiple, complementary
      techniques that provide accurate unit cell dimensions and molecular orientation
      is described. The combination of measurements results in a nearly complete
      picture of the organic film morphology.

PMID- 20809511
TI  - Near-infrared sunlight harvesting in dye-sensitized solar cells via the insertion
      of an upconverter-TiO2 nanocomposite layer.
AB  - Er(3+),Yb(3+) co-doped LaF3-TiO2 nanocomposites (UC-TiO2) are inserted as a
      middle layer in a novel tri-layer photoanode design (see Figure) of a dye
      sensitized solar cell (DSSC). The Er(3+),Yb(3+) co-doped LaF3 part of the
      nanocomposite helps capture near-infrared (NIR) light by converting it into
      visible light absorbable by the dye hence opening the road for the development of
      DSSCs with higher conversion efficiency and photocurrent output.

PMID- 20809512
TI  - Magnetic liquid marbles: a "precise" miniature reactor.

PMID- 20809513
TI  - Fabrication and efficiency improvement of soluble blue phosphorescent organic
      light-emitting diodes using a multilayer structure based on an alcohol-soluble
      blue phosphorescent emitting layer.

PMID- 20809514
TI  - Yarn-like carbon nanotube fibers.

PMID- 20809515
TI  - Bio-inspired hierarchical macromolecule-nanoclay hydrogels for robust underwater
      superoleophobicity.

PMID- 20809516
TI  - Bottom-up fabricated asymmetric electrodes for organic electronics.

PMID- 20809517
TI  - Photocoercivity of nano-stabilized Au: Fe superparamagnetic nanoparticles.

PMID- 20809518
TI  - Ultrasensitive detection of DNA molecules with high on/off single-walled carbon
      nanotube network.

PMID- 20809519
TI  - A matter of timing: early, not chronic phase intestinal nematode infection
      restrains control of a concurrent enteric protozoan infection.
AB  - Infections with parasitic worms are often long lasting and associated with
      modulated immune responses. We analyzed the influence of the nematode
      Heligmosomoides polygyrus bakeri dwelling in the small intestine on concurrent
      protozoan infection with Eimeria falciformis residing in the cecum. To dissect
      the effects of a nematode infection in the early versus chronic phase, we
      infected animals with E. falciformis 6 or 28 days post H. p. bakeri infection.
      Only a concurrent early nematode infection led to an increased replication of the
      protozoan parasite, whereas a chronic worm infection had no influence on the
      control of E. falciformis. Increased protozoan replication correlated with the
      reduced production of IFN-gamma, IL-12/23, CCL4, CXCL9 and CXCL10, reduced
      migration of T cells and increased expression of Foxp3 at the site of protozoan
      infection. This was accompanied by a stronger nematode-specific Th2 response in
      gut-draining LN. Protection of mice against challenge infections with the
      protozoan parasite was not altered. Hence, the detrimental effect of a nematode
      infection on the control of a concurrent protozoan infection is transient and
      occurs only in the narrow time window of the early phase of infection.

PMID- 20809520
TI  - FcgammaRIIB regulation of BCR/TLR-dependent autoreactive B-cell responses.
AB  - Crosslinking of Fc gamma receptor II B (FcgammaRIIB) and the BCR by immune
      complexes (IC) can downregulate antigen-specific B-cell responses. Accordingly,
      FcgammaRIIB deficiencies have been associated with B-cell hyperactivity in
      patients with systemic lupus erythematosus and mouse models of lupus. However, we
      have previously shown that murine IgG2a-autoreactive AM14 B cells respond
      robustly to chromatin-associated IC through a mechanism dependent on both the BCR
      and the endosomal TLR9, despite FcgammaRIIB coexpression. To further evaluate the
      potential contribution of FcgammaRIIB to the regulation of autoreactive B cells,
      we have now compared the IC-triggered responses of FcgammaRIIB-deficient and
      FcgammaRIIB-sufficient AM14 B cells. We find that FcgammaRIIB-deficient cells
      respond significantly better than FcgammaRIIB-sufficient cells when stimulated
      with DNA IC that incorporate low-affinity TLR9 ligand (CG-poor dsDNA fragments).
      AM14 B cells also respond to RNA-associated IC through BCR/TLR7 coengagement, but
      such BCR/TLR7-dependent responses are normally highly dependent on IFN-alpha
      costimulation. However, we now show that AM14 FcgammaRIIB(-/-) B cells are very
      effectively activated by RNA IC without supplemental IFN-alpha priming. These
      results demonstrate that FcgammaRIIB can effectively modulate both BCR/TLR9 and
      BCR/TLR7 endosomal-dependent activation of autoreactive B cells.

PMID- 20809522
TI  - IL-10 produced by activated human B cells regulates CD4(+) T-cell activation in
      vitro.
AB  - IL-10-producing regulatory B cells have been identified in mice and shown to
      downregulate inflammation, making them potentially important for maintenance of
      tolerance. In this study, we isolated B cells from human blood and spleen, and
      showed that after a short period of ex vivo stimulation a number of these cells
      produced IL-10. The IL-10-producing B cells did not fall within a single clearly
      defined subpopulation, but were enriched in both the memory (CD27(+)) and the
      transitional (CD38(high)) B-cell compartments. Combined CpG-B+anti-Ig stimulation
      was the most potent IL-10 stimulus tested. B cells stimulated in this way
      inhibited CD4(+)CD25(-) T-cell proliferation in vitro by a partially IL-10
      dependent mechanism. These findings imply that manipulating IL-10 production by
      human B cells could be a useful therapeutic strategy for modulating immune
      responses in humans.

PMID- 20809521
TI  - Islet-expressed TLR2 and TLR4 sense injury and mediate early graft failure after
      transplantation.
AB  - Although islet transplantation is an effective treatment for Type 1 diabetes,
      primary engraftment failure contributes to suboptimal outcomes. We tested the
      hypothesis that islet isolation and transplantation activate innate immunity
      through TLR expressed on islets. Murine islets constitutively express TLR2 and
      TLR4, and TLR activation with peptidoglycan or LPS upregulates islet production
      of cytokines and chemokines. Following transplantation into streptozotocin
      induced diabetic, syngeneic mice, islets exposed to LPS or peptidoglycan had
      primary graft failure with intra- and peri-islet mononuclear cell inflammation.
      The use of knockout mice showed that recipient CD8(+) T cells caused engraftment
      failure and did so in the absence of islet-derived DC. To mimic physiological
      islet injury, islets were transplanted with exocrine debris. Transplantation of
      TLR2/4(-/-) islets reduced proinflammatory cytokine production and improved islet
      survival. Stressed islets released the alarmin high-mobility group box protein 1
      (HMGB1) and recombinant HMGB1 (rHMGB1) induced NFkB activation. NFkB activation
      was prevented in the absence of both TLR2 and TLR4. rHMGB1 pretreatment also
      prevented primary engraftment through a TLR2/4-dependent pathway. Our results
      show that islet graft failure can be initiated by TLR2 and TLR4 signaling and
      suggest that HMGB1 is one likely early mediator. Subsequent downstream signaling
      results in intra-islet inflammation followed by T-cell-mediated graft
      destruction.

PMID- 20809523
TI  - A hierarchical Bayesian approach to multiple testing in disease mapping.
AB  - We propose a Bayesian approach to multiple testing in disease mapping. This study
      was motivated by a real example regarding the mortality rate for lung cancer,
      males, in the Tuscan region (Italy). The data are relative to the period 1995
      1999 for 287 municipalities. We develop a tri-level hierarchical Bayesian model
      to estimate for each area the posterior classification probability that is the
      posterior probability that the municipality belongs to the set of non-divergent
      areas. We show also the connections of our model with the false discovery rate
      approach. Posterior classification probabilities are used to explore areas at
      divergent risk from the reference while controlling for multiple testing. We
      consider both the Poisson-Gamma and the Besag, York and Mollie model to account
      for extra Poisson variability in our Bayesian formulation. Posterior inference on
      classification probabilities is highly dependent on the choice of the prior. We
      perform a sensitivity analysis and suggest how to rely on subject-specific
      information to derive informative a priori distributions. Hierarchical Bayesian
      models provide a sensible way to model classification probabilities in the
      context of disease mapping.

PMID- 20809524
TI  - Fabrication of paclitaxel nanocrystals by femtosecond laser ablation and
      fragmentation.
AB  - Nanonization, which involves formulating the drug powder as nanometer-sized
      particles, is a known method to improve drug absorption and allow the intravenous
      administration of insoluble drugs. This study investigated a novel femtosecond
      (fs) laser technique for the fabrication of nanocrystals in aqueous solution of
      the insoluble model drug paclitaxel. Two distinct methods of this technology,
      ablation and fragmentation, were investigated and the influence of laser power,
      focusing position and treatment time on the particle size, drug concentration,
      and degradation was studied. The colloidal suspensions were characterized with
      respect to size, chemical composition, morphology, and polymorphic state. Optimal
      laser fragmentation conditions generated uniformly sized paclitaxel nanoparticles
      (<500 nm) with quantifiable degradation, while ablation followed by fragmentation
      was associated with a larger polydispersity. Laser treatment at higher powers
      produced smaller particles with larger amount of degradation. The crystalline
      morphology of the drug was retained upon nanonization, but the anhydrous crystals
      were converted to a hydrated form, a phenomenon also observed during bead
      milling. These findings suggest that drug nanocrystals can be produced with fs
      laser technology using very little drug quantities, which may be an asset for
      preclinical evaluation of new drug candidates.

PMID- 20809525
TI  - Molecular spectrum of autosomal dominant hypercholesterolemia in France.
AB  - Autosomal Dominant Hypercholesterolemia (ADH), characterized by isolated
      elevation of plasmatic LDL cholesterol and premature cardiovascular
      complications, is associated with mutations in 3 major genes: LDLR (LDL
      receptor), APOB (apolipoprotein B) and PCSK9(proprotein convertase subtilisin
      kexin type 9). Through the French ADH Research Network, we collected molecular
      data from 1358 French probands from eleven different regions in France.Mutations
      in the LDLR gene were identified in 1003 subjects representing 391 unique events
      with 46.0% missense, 14.6% frameshift, 13.6% splice, and 11.3% nonsense
      mutations, 9.7% major rearrangements, 3.8% small in frame deletions/insertions,
      and 1.0% UTR mutations. Interestingly,175 are novel mutational events and
      represent 45% of the unique events we identified, highlighting a specificity of
      the LDLR mutation spectrum in France. Furthermore, mutations in the APOB gene
      were identified in 89 probands and in the PCSK9 gene in 10 probands. Comparison
      of available clinical and biochemical data showed a gradient of severity for ADH
      causing mutations:FH=PCSK9>FDB>"Others" genes. The respective contribution of
      each known gene to ADH inthis French cohort is: LDLR 73.9%, APOB 6.6%, PCSK9
      0.7%. Finally, in 19.0% of the probands,no mutation was found, thus underscoring
      the existence of ADH mutations located in still unknown genes.

PMID- 20809526
TI  - A rare novel deletion of the tyrosine hydroxylase gene in Parkinson disease.
AB  - Tyrosine hydroxylase (TH) enzyme is a rate limiting enzyme in dopamine
      biosynthesis. Missense mutation in both alleles of the TH gene is known to cause
      dopamine-related phenotypes, including dystonia and infantile Parkinsonism.
      However, it is not clear if single allele mutation in TH modifies the
      susceptibility to the adult form of Parkinson disease (PD). We reported a novel
      deletion of entire TH gene in an adult with PD. The deletion was first identified
      by copy number variation (CNV) analysis in a genome-wide association study using
      Illumina Infinium BeadChips. After screening 635 cases and 642 controls, the
      deletion was found in one PD case but not in any control. The deletion was
      confirmed by multiple quantitative PCR (qPCR) assays. There is no additional
      exonic single nucleotide variant in the one copy of TH gene of the patient. The
      patient has an age-at-onset of 54 years, no evidence for dystonia, and was
      responsive to L-DOPA. This case supports the importance of the TH gene in PD
      pathogenesis and raises more attention to rare variants in candidate genes being
      a risk factor for Parkinson disease.

PMID- 20809527
TI  - LQTS gene LOVD database.
AB  - The Long QT Syndrome (LQTS) is a group of genetically heterogeneous disorders
      that predisposes young individuals to ventricular arrhythmias and sudden death.
      LQTS is mainly caused by mutations in genes encoding subunits of cardiac ion
      channels (KCNQ1, KCNH2,SCN5A, KCNE1, and KCNE2). Many other genes involved in
      LQTS have been described recently(KCNJ2, AKAP9, ANK2, CACNA1C, SCNA4B, SNTA1, and
      CAV3). We created an online
      database(http://www.genomed.org/LOVD/introduction.html) that provides information
      on variants in LQTS-associated genes. As of February 2010, the database contains
      1738 unique variants in 12 genes. A total of 950 variants are considered
      pathogenic, 265 are possible pathogenic, 131 are unknown/unclassified, and 292
      have no known pathogenicity. In addition to these mutations collected from
      published literature, we also submitted information on gene variants, including
      one possible novel pathogenic mutation in the KCNH2 splice site found in ten
      Chinese families with documented arrhythmias. The remote user is able to search
      the data and is encouraged to submit new mutations into the database. The LQTS
      database will become a powerful tool for both researchers and clinicians.

PMID- 20809528
TI  - MicroSNiPer: a web tool for prediction of SNP effects on putative microRNA
      targets.
AB  - MicroRNAs are short, approximately 22 nucleotide noncoding RNAs binding to
      partially complementary sites in the 3'UTR of target mRNAs. This process
      generally results in repression of multiple targets by a particular microRNA.
      There is substantial interest in methods designed to predict the microRNA targets
      and effect of single nucleotide polymorphisms (SNPs) on microRNA binding, given
      the impact of microRNA on posttranscriptional regulation and its potential
      relation to complex diseases. We developed a web-based application, MicroSNiPer,
      which predicts the impact of a SNP on putative microRNA targets. This application
      interrogates the 3'-untranslated region and predicts if a SNP within the target
      site will disrupt/eliminate or enhance/create a microRNA binding site.
      MicroSNiPer computes these sites and examines the effects of SNPs in real time.
      MicroSNiPer is a user-friendly Web-based tool. Its advantages include ease of
      use, flexibility, and straightforward graphical representation of the results. It
      is freely accessible at http://cbdb.nimh.nih.gov/microsniper.

PMID- 20809532
TI  - Quality assessment and improvement in diabetes care-an issue now and for the
      future.
AB  - Damin and colleagues in this issue of DMRR Assessing quality of diabetes care and
      its variation in Aboriginal community health centres in Australia reviewed the
      quality of diabetes care and its variation among Aboriginal community health
      centres. They assessed partitioning of variation attributable to health centre
      and individual patient characteristics. The results demonstrated wide variation
      across different categories of diabetes care measures and across centres.

PMID- 20809529
TI  - Molecular mechanisms leading to null-protein product from retinoschisin (RS1)
      signal-sequence mutants in X-linked retinoschisis (XLRS) disease.
AB  - Retinoschisin (RS1) is a cell-surface adhesion molecule expressed by
      photoreceptor and bipolar cells of the retina. The 24-kDa protein encodes two
      conserved sequence motifs: the initial signal sequence targets the protein for
      secretion while the larger discoidin domain is implicated in cell adhesion. RS1
      helps to maintain the structural organization of the retinal cell layers and
      promotes visual signal transduction. RS1 gene mutations cause X-linked
      retinoschisis disease (XLRS) in males, characterized by early-onset central
      vision loss. We analyzed the biochemical consequences of several RS1 signal
      sequence mutants (c.1A>T, c.35T>A, c.38T>C, and c.52G>A) found in our subjects.
      Expression analysis in COS-7 cells demonstrates that these mutations affect RS1
      biosynthesis and result in an RS1 null phenotype by several different mechanisms.
      By comparison, discoidin-domain mutations generally lead to nonfunctional
      conformational variants that remain trapped inside the cell. XLRS disease has a
      broad heterogeneity in general, but subjects with the RS1 null-protein signal
      sequence mutations are on the more severe end of the clinical phenotype. Results
      from the signal-sequence mutants are discussed in the context of the discoidin
      domain mutations, clinical phenotypes, genotype-phenotype correlations, and
      implications for RS1 gene replacement therapy.

PMID- 20809533
TI  - Asiatic acid preserves beta cell mass and mitigates hyperglycemia in streptozocin
      induced diabetic rats.
AB  - BACKGROUND: Type 1 diabetes is a chronic condition in which the pancreas produces
      little or no insulin due to the loss or dysfunction of pancreatic beta cells.
      This study investigated the beneficial effects of asiatic acid-a triterpenoid
      compound-preserved beta mass and mitigated hyperglycemia in streptozocin-induced
      diabetic rats. METHODS: Diabetes mellitus was induced in adult male Wistar rats
      by a single intraperitoneal injection of streptozocin (60 mg/kg body weight). The
      diabetic rats were divided into untreated and asiatic acid (25 mg/kg) groups.
      Controls were intraperitoneal injection with citrate buffer. Blood glucose level,
      plasma insulin, and pancreas immunohistochemistry analysis were examined after a
      2-week experimental period. AKT and Bcl-xL expression in the pancreatic islets of
      rats were evaluated by Western blot methods. RESULTS: Blood glucose levels were
      significantly reduced in rats receiving asiatic acid after streptozocin
      administration. Asiatic acid concomitantly increased serum insulin levels in
      diabetic rats. Immunohistochemical staining revealed a marked preservation by
      asiatic acid of insulin-producing beta cells in the pancreatic islets of the
      diabetic rats. Furthermore, asiatic acid in vivo induced pro-survival Akt kinase
      activation and Bcl-xL expression in the pancreatic islets of diabetic rats.
      CONCLUSIONS: These results suggest that asiatic acid exerts its glucose-lowering
      effects, in part through influences on beta-cell mass. Asiatic acid
      administration resulted in preservation and restoration of beta-cell mass and
      function in diabetic rodent models.

PMID- 20809534
TI  - Osteoprotegerin and biomarkers of vascular inflammation in type 2 diabetes.
AB  - BACKGROUND: Osteoprotegerin (OPG), receptor activator for nuclear factor kappa
      beta ligand (RANKL) and tumour necrosis factor-related apoptosis-inducing ligand
      (TRAIL) are newly discovered members of the tumour necrosis factor-alpha receptor
      superfamily. While their role in bone metabolism is well described, their
      function within the vasculature is poorly understood. OPG inhibits vascular
      calcification in vitro and high serum levels have been demonstrated in type 2
      diabetes, but serum RANKL and TRAIL and their potential correlation with well
      established biomarkers of subclinical vascular inflammation such as high
      sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) have not been
      described. METHODS: Sixty-two patients with well-controlled type 2 diabetes and
      an age, gender and body mass index-matched group of 58 healthy individuals were
      recruited. Serum OPG, RANKL and TRAIL were measured using commercial enzyme
      linked immunosorbent assays, as were hsCRP and IL-6. RESULTS: Serum OPG, IL-6 and
      hsCRP levels, but not RANKL or TRAIL, were higher in patients with type 2
      diabetes mellitus than in healthy controls, after adjustment for age and gender.
      After exclusion of diabetes patients with a history of micro- or macrovascular
      disease, OPG remained significantly higher in those with diabetes, but IL-6 and
      hsCRP levels were no longer elevated. There was a positive correlation between
      OPG and IL-6 in the group as a whole, but no correlation was found between RANKL
      or TRAIL and either hsCRP or IL-6. CONCLUSION: OPG, but not RANKL or TRAIL, is
      significantly increased in type 2 diabetes. Higher OPG (but not IL-6 or hsCRP) in
      those without vascular disease suggests these biomarkers reflect separate
      pathophysiological processes in the vasculature.

PMID- 20809536
TI  - Introduction and snapshot review: relating infectious disease transmission models
      to data.
AB  - Disease transmission models are becoming increasingly important both to public
      health policy makers and to scientists across many disciplines. We review some of
      the key aspects of how and why such models are related to data from infectious
      disease outbreaks, and identify a number of future challenges in the field.

PMID- 20809537
TI  - Analyzing multivariate survival data using composite likelihood and flexible
      parametric modeling of the hazard functions.
AB  - In this paper, we model multivariate time-to-event data by composite likelihood
      of pairwise frailty likelihoods and marginal hazards using natural cubic splines.
      Both right- and interval-censored data are considered. The suggested approach is
      applied on two types of family studies using the gamma- and stable frailty
      distribution: The first study is on adoption data where the association between
      survival in families of adopted children and their adoptive and biological
      parents is studied. The second study is a cross-sectional study of the occurrence
      of back and neck pain in twins, illustrating the methodology in the context of
      genetic epidemiology.

PMID- 20809538
TI  - Comparison of weighted kappa coefficients of multiple binary diagnostic tests
      done on the same subjects.
AB  - Sensitivity and specificity are classic parameters to assess and compare the
      performance of binary diagnostic tests versus a gold standard in a population.
      Another useful parameter to assess and compare the performance of binary tests is
      the weighted kappa coefficient, which is defined as a measure of the beyond
      chance agreement between the diagnostic test and the gold standard. In this
      study, we deduce the maximum likelihood estimators of the weighted kappa
      coefficients of multiple binary tests and we propose an asymptotic method to
      compare the weighted kappa coefficients of multiple binary tests with regard to
      the same gold standard when all of the diagnostic tests are applied to the same
      sample of patients. We have carried out simulation experiments to study the type
      I error and the power of the method that we propose when we compared three binary
      tests. We have applied the results obtained to the diagnosis of coronary disease.

PMID- 20809541
TI  - Estimation of absorption of aromatic hydrocarbons diffusing from interior
      materials in automobile cabins by inhalation toxicokinetic analysis in rats.
AB  - Aromatic hydrocarbons, as well as aliphatic hydrocarbons, diffusing from interior
      materials in automotive cabins are the most common compounds contributing to
      interior air pollution. In this study, the amounts of seven selected aromatic
      hydrocarbons absorbed by a car driver were estimated by evaluating their
      inhalation toxicokinetics in rats. Measured amounts of these substances were
      injected into a closed chamber system containing a rat, and the concentration
      changes in the chamber were examined. The toxicokinetics of the substances were
      evaluated on the basis of the concentration-time course using a nonlinear
      compartment model. The amounts absorbed in humans at actual concentrations in
      automobile cabins without ventilation were extrapolated from the results obtained
      from rats. The absorbed amounts estimated for a driver during a 2 h drive were as
      follows (per 60 kg of human body weight): 30 microg for toluene (interior median
      concentration, 40 microg m(-3) in our previous study), 10 microg for ethylbenzene
      (12 microg m(-3)), 6 microg for o-xylene (10 microg m(-3)), 8 microg for m-xylene
      (11 microg m(-3)), 9 microg for p-xylene (11 microg m(-3)), 11 microg for styrene
      (11 microg m(-3)) and 27 microg for 1,2,4-trimethylbenzene (24 microg m(-3)).
      Similarly, in a cabin where air pollution was marked, the absorbed amount of
      styrene (654 microg for 2 h in a cabin with an interior maximum concentration of
      675 microg m(-3)) was estimated to be much higher than those of other substances.
      This amount (654 microg) was approximately 1.5 times the tolerable daily intake
      of styrene (7.7 microg kg(-1) per day) recommended by the World Health
      Organization.

PMID- 20809542
TI  - Differential ablation of sensory receptors underlies ototoxin-induced shifts in
      auditory thresholds of the goldfish (Carassius auratus).
AB  - In recent years, fish models have become popular for investigations of ototoxic
      agents. However, the vast majority of such studies have focused on anatomical
      changes in lateral line hair cells after drug administration. Using the goldfish
      (Carassius auratus), we confirm that the acquisition of auditory evoked
      potentials offers a rapid and non-invasive method for quantifying ototoxin
      induced changes in hearing sensitivity. Gentamicin (100 mg ml(-1)) was the drug
      of choice as it is a well-studied human ototoxin. Auditory threshold elevation
      was observed between 300 and 600 Hz and was accompanied by significant reductions
      in hair cell ciliary bundle densities in specific regions of the utricle and
      saccule. The correlations between structure and function suggest that
      differential susceptibility of sensory hair cells to acute gentamicin treatment
      underlies the frequency-specific elevation of auditory thresholds. We propose
      that fish auditory systems should be used alongside the lateral line, for the
      assessment of ototoxicity in new-developed drugs.

PMID- 20809543
TI  - Assessment of isorhamnetin 3-O-neohesperidoside from Acacia salicina: protective
      effects toward oxidation damage and genotoxicity induced by aflatoxin B1 and
      nifuroxazide.
AB  - Antioxidant activity of isorhamnetin 3-O-neohesperidoside, isolated from the
      leaves of Acacia salicina, was determined by the ability of this compound to
      inhibit xanthine oxidase activity and to scavenge the free radical 2,2'-azino-bis
      (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS(.-)) diammonium salt. Antigenotoxic
      activity was assessed using the SOS chromotest assay. This compound has the
      ability to scavenge the ABTS(.+) radical by a hydrogen donating mechanism. We
      also envisaged the study of the antioxidant effect of this compound by the
      enzymatic xanthine/xanthine oxidase (X/XOD) assay. Results indicated that
      isorhamnetin 3-O-neohesperidoside was a potent inhibitor of xanthine oxidase and
      superoxide anion scavengers. Moreover, this compound induced an inhibitory
      activity against nifuroxazide and aflatoxine B1 (AFB1) induced genotoxicity.
      Taken together, these observations provide evidence that isorhamnetin 3-O
      neohesperidoside isolated from the leaves of A. salicina is able to protect cells
      against the consequences of oxidative stress.

PMID- 20809544
TI  - Dichlorvos, chlorpyrifos oxon and Aldicarb adducts of butyrylcholinesterase,
      detected by mass spectrometry in human plasma following deliberate overdose.
AB  - The goal of this study was to develop a method to detect pesticide adducts in
      tryptic digests of butyrylcholinesterase in human plasma from patients poisoned
      by pesticides. Adducts to butyrylcholinesterase in human serum may serve as
      biomarkers of pesticide exposure because organophosphorus and carbamate
      pesticides make a covalent bond with the active site serine of
      butyrylcholinesterase. Serum samples from five attempted suicides (with
      dichlorvos, Aldicarb, Baygon and an unknown pesticide) and from one patient who
      accidentally inhaled dichlorvos were analyzed. Butyrylcholinesterase was purified
      from 2 ml serum by ion exchange chromatography at pH 4, followed by procainamide
      affinity chromatography at pH 7. The purified butyrylcholinesterase was
      denatured, digested with trypsin and the modified peptide isolated by HPLC. The
      purified peptide was analyzed by multiple reaction monitoring in a QTRAP 4000
      mass spectrometer. This method successfully identified the pesticide-adducted
      butyrylcholinesterase peptide in four patients whose butyrylcholinesterase was
      inhibited 60-84%, but not in two patients whose inhibition levels were 8 and 22%.
      It is expected that low inhibition levels will require analysis of larger serum
      plasma volumes. In conclusion, a mass spectrometry method for identification of
      exposure to live toxic pesticides has been developed, based on identification of
      pesticide adducts on the active site serine of human butyrylcholinesterase.

PMID- 20809545
TI  - Comparative hepatotoxicity of deoxynivalenol in rat, mouse and human liver cells
      in culture.
AB  - The present study was undertaken to assess, in vitro, the hepatotoxic potential
      of the food-borne mycotoxin, deoxynivalenol (DON), using rat (Clone9 and MH1C1),
      mouse (NBL CL2) and human (WRL68 and HepG2) liver cells in culture. The cells
      were treated with DON for 24 h at 37 degrees C in 5% CO(2) at concentrations of 0
      25 microg ml(-1). Following the treatment period, the cells were assayed for
      biochemical markers of hepatotoxicity that included three independent
      cytotoxicity assays, oxidative stress and mitochondrial dysfunction.
      Concentration-dependent cytotoxicity of DON was observed in each of the five
      different liver cells derived from three different species (rat, mouse and human)
      over the entire concentration range studied, beginning at 0.1 microg ml(-1). At
      these concentrations DON did not induce a biologically significant increase in
      oxidative stress in these liver cells, and showed a significant decrease in the
      mitochondrial function only in the rat liver MH1C1 cells compared with the
      control. The results of this in vitro study suggest that DON is a potential
      hepatotoxin for the rat, mouse and human liver cells in the concentration range
      tested in this study. The liver cells used in this study showed distinct endpoint
      sensitivity to DON related to the species.

PMID- 20809546
TI  - Conservation of the chromatophore pigment response.
AB  - Toxicant sensing technology has evolved to include biological sensors, such as
      cell-based biosensors, which rely on viable cells to convey a measurable
      physiological signal. Chromatophores are a class of pigment cells that have been
      investigated as cell-based biosensors. We report the characterization of
      Oncorhynchus tshawytscha melanophores and describe the melanophore pigment
      response to neurotransmitters in terms of pigment area occupied. Compared with
      the previously described model, Betta splendens erythrophores, O. tshawytscha
      melanophores responded similarly, indicating that pigment responses are
      biologically conserved between these two species. Additionally, melanophores
      responded to mercuric chloride and sodium arsenite, similar to B. splendens
      erythrophores, suggesting that melanophores can be used as detectors for
      environmental toxicants. This report highlights the potential of O. tshawytscha
      melanophores to be used as cell-based biosensors to address environmental
      toxicity, and warrants a continued investigation to strengthen this technology
      and its applications.

PMID- 20809547
TI  - Acute atrazine exposure disrupts matrix metalloproteinases and retinoid signaling
      during organ morphogenesis in Xenopus laevis.
AB  - Exposure to the herbicide atrazine disrupts many developmental processes in non
      target animals. Atrazine exposure during organ morphogenesis in amphibians
      results in dramatic malformations; the mechanism by which this happens has not
      been described. We have taken a candidate gene approach to explore two possible
      mechanisms by which acute atrazine exposure causes extensive malformations in
      several tissues in Xenopus laevis tadpoles. Using a static renewal system, we
      exposed tadpoles to atrazine for 6-48 h during organ morphogenesis (Nieuwkoop and
      Faber stage 42). We observed degradation of cranial cartilage and differentiated
      muscle in the head, gut and somites of exposed tadpoles. Additionally, transcript
      levels of matrix metalloproteinases (MMPs), specifically both MMP9TH and MMP18,
      increased in atrazine-exposed tadpoles in a dose-response test, and MMP18
      increased as early as 6 h after exposure began. Gelatinase MMP activity was also
      altered by atrazine exposure, indicating that atrazine disrupts gene function at
      the level of transcription and protein activity. Furthermore, transcript levels
      of the enzyme Xcyp26, an enzyme in the retinoic acid signaling pathway,
      significantly decreased in the intestines of tadpoles exposed to 10 or 35 mg l(
      1) atrazine for 48 h. Our results suggest two mechanisms by which atrazine can
      disrupt tissue morphogenesis: through misregulation of MMPs that are critical in
      extracellular matrix remodeling throughout development and the disruption of
      retinoic acid signaling. This study begins to describe conserved vertebrate
      developmental processes that are disrupted by atrazine exposure.

PMID- 20809548
TI  - Oxidative stress biomarkers in Cyprinus carpio exposed to commercial herbicide
      bispyribac-sodium.
AB  - Cyprinus carpio were exposed under field conditions to 20.87 microg l(-1) of
      commercial herbicide bispyribac-sodium (Nominee, SC), during 7, 21 and 72 days.
      Enzymatic parameters such as catalase (CAT), glutathione S-transferase (GST) and
      acetylcholinesterase (AChE) activities, as well as thiobarbituric acid-reactive
      substances (TBARS) and protein carbonyl contents were studied in different
      tissues. After 7 days of exposure, GST activity decreased. At the same period,
      brain AChE activity increased, but a reduction of activity was observed in muscle
      tissue. Brain TBARS levels increased at 7 days. After 21 days of exposure liver
      CAT levels and muscle AChE activities decreased. In the same period, liver
      protein carbonyl and muscle TBARS increased. After 72 days of exposure in the
      field, AChE activity was reduced in both brain and muscle. Protein carbonyl
      contents in liver and brain TBARS levels increased. Muscle AChE activity, TBARS
      and protein carbonyl can be used as biomarkers of exposure to the herbicide
      bispyribac-sodium. This study demonstrates effects of exposure to bispyribac
      sodium under rice field conditions on oxidative stress parameters in tissues of
      Cyprinus carpio.

PMID- 20809549
TI  - Genotoxicity evaluation of two kinds of smoke-water and 3,7-dimethyl-2H-furo[2,3
      c]pyran-2-one.
AB  - Smoke, smoke-water and aerosols have a stimulatory effect on seed germination and
      growth vigour of many seedlings, making them potentially useful for different
      purposes, provided they do not pose a health risk. Therefore, the genotoxicity of
      two kinds of smoke-water and 3,7-dimethyl-2H-furo[2,3-c]pyran-2-one, a variant of
      the most active smoke compound (3-methyl-2H-furo[2,3-c]pyran-2-one) was evaluated
      using the Vitotox assay. Smoke-water extracts were obtained from burning leaves:
      Themeda triandra (smoke-water Tt) and a mix of Themeda triandra and Passerina
      vulgaris (smoke-water Kb). No genotoxic effect was observed for any of the three
      samples. However, the three samples are toxic at the highest concentrations (3,7
      dimethyl-2H-furo[2,3-c]pyran-2-one, 2 ppm; smoke-water Tt, dilutions 1 : 1, 1 :
      2, 1 : 4; smoke-water Kb, dilution 1 : 1) without addition of S9 mix. Both the
      butenolide 3,7-dimethyl-2H-furo[2,3-c]pyran-2-one and smoke-water Tt are also
      toxic at high doses in the presence of S9 (2 ppm and dilutions 1 : 1 and 1 : 2,
      respectively), but not smoke-water Kb. Thus, from these results, no genotoxicity
      of these three samples can be assumed, which is accordance with the previous
      tests performed with 3-methyl-2H-furo[2,3-c]pyran-2-one and a smoke-water.

PMID- 20809550
TI  - In vitro cellular responses in the RTG-2 cell line to complex mixtures of dioxins
      and dioxin-like PCDDs, PCDFs and PCBs.
AB  - High-resolution gas chromatography/mass spectrometry (HRGC/MS) is the standard
      method for analysing dioxin, furan and polybrominated retardants in hazardous
      waste. Determination of dioxin-like compounds using in vitro bioassays such as
      ethoxyresorufin-O-deethylase (EROD) is an important tool to evaluate their Ah
      receptor-mediated toxic effects, because it detects all arylhydrocarbon receptor
      ligands in a variety of sample matrices. In the present work, we compared RTG-2
      cell line EROD bioassay with HRGC/MS for assessing waste samples (liquid and
      solid) contaminated with polychlorinated dibenzo-p-dioxins and dibenzofurans,
      polychlorinated biphenyls (dioxin-like PCBs) and other xenobiotics. For liquid
      samples, HRGC/MS-toxic equivalent (HRGC/MS-TEQ) values ranged from 273.26 to 5.84
      ng TEQ l(-1) and correlated well (correlation coefficient 0.99) with values
      obtained by EROD-TEQ, which ranged from 128 to 2.5 ng TEQ l(-1). For solid
      samples, HRGC/MS-TEQ values ranged from 3.44 to 0.49 ng TEQ g(-1) and correlated
      less well than liquid samples (correlation coefficient 0.64) with values obtained
      by EROD-TEQ ranging from 2.27 to 0.93 ng TEQ g(-1). The overestimation of RTG-2
      EROD-TEQ (1.2 +/- 0.92 of values established by HRGC/MS) and the absence of false
      negative results may limit analytical costs by eliminating the need for follow-up
      GC/MS analysis on the negative samples. We suggest that RTG-2 EROD bioassay is an
      inexpensive means for preliminary dioxin and furan positive screenings of waste
      samples.

PMID- 20809551
TI  - Inhibition of creatine kinase activity by 3-butyl-1-phenyl-2-(phenyltelluro)oct
      en-1-one in the cerebral cortex and cerebellum of young rats.
AB  - In the present study, we investigated the potential in vitro toxicity of the
      tellurium compound 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one on creatine
      kinase activity in cerebral cortex and cerebellum of 30-day-old Wistar rats.
      First, enriched mitochondrial and cytosolic fractions from the two tissues were
      pre-incubated for 30 min in the presence or absence of 1, 5 or 20 microm of
      organotellurium and the creatine kinase activity was measured. The
      organochalcogen reduced creatine kinase activity in a concentration-dependent
      pattern in the two tissues studied. Furthermore, the enzyme activity was
      performed after pre-incubation for 30, 60 or 90 min in the presence of 5 microm
      of the organotellurium. The compound inhibited creatine kinase activity in a time
      dependent way in the enriched mitochondrial fraction of both tissues, but not in
      the cytosolic fraction, indicating different mechanisms for the organochalcogen
      in the mitochondrial and in the cytosolic creatine kinase. Pre-incubation of
      tellurium compound with reduced glutathione suggests that creatine kinase
      activity inhibition might be caused by direct interaction with thiol groups or by
      oxidative stress. Our findings suggest that creatine kinase inhibition may be one
      of the mechanisms by which this organotellurium could cause toxicity to the rat
      brain.

PMID- 20809553
TI  - High level PSMA expression is associated with early PSA recurrence in surgically
      treated prostate cancer.
AB  - BACKGROUND: Prostate specific membrane antigen (PSMA) is a suggested target for
      antibody-based therapy of prostate cancer potentially involved in the regulation
      of cell migration. This study was undertaken, to gain more insight on the role of
      PSMA in early prostate cancer and its distribution in various normal tissues.
      METHODS: A total of 1,700 different prostate cancers treated by radical
      prostatectomy and 612 samples from 76 different normal tissue types were
      successfully analyzed by immunohistochemistry (IHC) in a tissue microarray (TMA)
      format. PSMA immunostaining in cancers was also compared with clinical follow-up,
      preexisting HER2 expression and Ki67 labeling index data. RESULTS: PSMA staining
      was only found in prostate epithelium and expression was higher in cancer cells
      than in benign tissue. PSMA staining was found in 94.1% of cancers and was
      significantly associated with tumor stage, high Gleason grade, preoperative PSA,
      and HER2 expression (P < 0.0001 each). Tumors with strong PSMA expression had a
      higher risk of biochemical recurrence than cancers with only weak PSMA staining
      intensity (P = 0.0483). There was no significant association between PSMA
      expression and Ki67 labeling index (P = 0.442). CONCLUSIONS: Based on the high
      frequency of PSMA overexpression in all stages and grades of prostate cancer and
      the high prevalence of PSMA overexpression, it can be speculated that increased
      PSMA expression may be related with prostate cancer development rather than
      progression. The known function of PSMA activating cell migration would be in
      line with the suggested role in cancer progression and the missing association
      between PSMA overexpression and tumor cell proliferation.

PMID- 20809552
TI  - Disulfiram is a DNA demethylating agent and inhibits prostate cancer cell growth.
AB  - BACKGROUND: The clinical success of the nucleoside analogs 5-aza-cytidine (5
      azaC) and 5-aza-2'deoxycytidine (5-aza-dC) as DNA methyltransferase (DNMT)
      inhibitors has spurred interest in the development of non-nucleoside inhibitors
      with improved pharmacologic and safety profiles. Because DNMT catalysis features
      attack of cytosine bases by an enzyme thiol group, we tested whether disulfiram
      (DSF), a thiol-reactive compound with known clinical safety, demonstrated DNMT
      inhibitory activity. METHODS: Inhibition of DNMT1 activity by DSF was assessed
      using methyltransferase activity assays with recombinant DNMT1. Next, prostate
      cancer cell lines were exposed to DSF and assessed for: i) reduction of global 5
      methyl cytosine ((5me)C) content using liquid chromatography/tandem mass
      spectrometry (LC-MS/MS); ii) gene-specific promoter demethylation by methylation
      specific PCR (MSP); and iii) gene-reactivation by real-time RT-PCR. DSF was also
      tested for growth inhibition using prostate cancer cell lines propagated in vitro
      in cell culture and in vivo as xenografts in nude mice. RESULTS: Disulfiram
      showed a dose-dependent inhibition of DNMT1 activity on a hemimethylated DNA
      substrate. In prostate cancer cells in culture, DSF exposure led to reduction of
      global genomic (5me)C content, increase in unmethylated APC and RARB gene
      promoters, and associated re-expression of these genes, but did not significantly
      alter prostate-specific antigen (PSA) expression. DSF significantly inhibited
      growth and clonogenic survival of prostate cancer cell lines in culture and
      showed a trend for reduced growth of prostate cancer xenografts. CONCLUSIONS:
      Disulfiram is a non-nucleoside DNMT1 inhibitor that can reduce global (5me)C
      content, reactivate epigenetically silenced genes, and significantly inhibit
      growth in prostate cancer cell lines.

PMID- 20809554
TI  - A unified strategy targeting the thiodiketopiperazine mycotoxins exserohilone,
      gliotoxin, the epicoccins, the epicorazines, rostratin A and aranotin.
AB  - A unified synthetic strategy directed towards mycotoxins belonging to the
      thiodiketopiperazine family is reported. The building blocks for a number of
      natural products--including exserohilone, gliotoxin, the epicoccins, the
      epicorazines, rostratin A and aranotin--have been synthesised stereoselectively
      from a common precursor. This key intermediate was constructed through an
      efficient and highly diastereoselective [2+2] cycloaddition between a ketene and
      an enecarbamate derived from L-pyroglutamic acid. The annelation of the second
      ring was accomplished through ring-closing metathesis and enol ether-olefin ring
      closing metathesis to provide both cis- and trans-annelated azabicyclic
      cyclohexenones, as well as an annelated seven-membered cyclic enol ether. A Pd
      catalysed elimination of allyl acetate gave rise to the cyclohexadienol structure
      of gliotoxin. Dimerisation of one building block to afford the diketopiperazine
      core was demonstrated.

PMID- 20809555
TI  - One-pot tandem catalysis: a concise route to fused bicyclic scaffolds from
      acyclic beta-ketoesters and alkynyl aldehydes.

PMID- 20809556
TI  - Interaction of epothilone B (patupilone) with microtubules as detected by two
      dimensional solid-state NMR spectroscopy.

PMID- 20809557
TI  - A bimetallic titanium catalyst for the enantioselective cyanation of aldehydes
      based on cooperative catalysis.

PMID- 20809558
TI  - Direct evidence of a surface quenching effect on size-dependent luminescence of
      upconversion nanoparticles.

PMID- 20809559
TI  - Catalytic asymmetric direct Henry reaction of ynals: short syntheses of (2S,3R)
      (+)-xestoaminol C and (-)-codonopsinines.

PMID- 20809560
TI  - Stem Cells' position statement on hESC research.

PMID- 20809561
TI  - Synergistic and inhibitory effects of aminopeptidase peptides on Bacillus
      thuringiensis Cry11Ba toxicity in the mosquito Anopheles gambiae.
AB  - Cry11Ba produced by Bacillus thuringiensis subsp. jegathesan is an active toxin
      for larvae of the mosquito Anopheles gambiae. A 106-kDa aminopeptidase N (APN),
      called AgAPN2, was previously identified as a Cry11Ba receptor in A. gambiae. A
      70-kDa fragment of AgAPN2 expressed in Escherichia coli binds Cry11Ba with high
      affinity (K(d) = 6.4 nM) and inhibits Cry11Ba activity by 98% in bioassays [Zhang
      et al. (2008) Biochemistry 47, 11263-11272]. To identify regions involved in
      toxicity, we truncated the 70-kDa APN fragment into peptides of 28- and 30-kDa ta
      and tb, respectively, and tested their abilities to mediate toxicity and bind
      Cry11Ba. While AgAPN2ta reduced Cry11Ba toxicity by 85%, AgAPN2tb showed a
      significant enhancement effect on Cry11Ba toxicity. The purified peptides showed
      evidence of structural folding and bound the same site(s) on Cry11Ba with high
      affinity. The inhibitory AgAPN2ta blocked Cry11Ba binding to brush border
      membrane vesicles (BBMV) of A. gambiae whereas the toxicity enhancing AgAPN2tb
      increased Cry11Ba binding on BBMV. A deletion at the N-terminus ((336)S-P(420))
      of AgAPN2ta significantly reduced AgAPN2ta binding to Cry11Ba and its inhibitory
      effect. Deletion of the central region ((676)I-W(760)) of AgAPN2tb eliminated its
      increased toxin binding and toxicity enhancement effect without affecting Cry11Ba
      binding. A "bridge" model is proposed for AgAPN2tb action whereby the peptide
      binds Cry11Ba and vectors it to sites on the larval midgut.

PMID- 20809563
TI  - Fluidic timers for time-dependent, point-of-care assays on paper.
AB  - This article describes an integrated approach to tracking the end point of a time
      based assay that is conducted on an analytical device made out of paper. The
      timing mechanism is built directly into a paper-based analytical device and does
      not require starting, stopping, reset buttons, batteries, or maintenance; the
      timer simply starts once the sample is added to the device. These "fluidic
      timers" are composed of paraffin wax and a signaling feature (e.g., a dye). The
      timing function is made possible by the specific time required for a liquid
      sample to wick through predefined regions in the device. This time period can be
      anywhere between 1 min and 2 h and is controlled by the quantity of wax present
      in the timer. Because both the fluidic timers and paper-based assays depend on
      the wicking rate of the sample, the fluidic timers automatically calibrate
      themselves (relative to the assay) to account for differences in wicking rates
      that are caused by variations in humidity. Fluidic timers are 97% accurate (with
      respect to the time required for the assay) and provide slightly better accuracy
      than an external timer when used to track an assay that measured the level of
      glucose in a sample.

PMID- 20809564
TI  - Online size exclusion chromatography-NMR for the determination of molar mass
      distributions of copolymers.
AB  - A general approach of size exclusion chromatography (SEC)-NMR is introduced for
      the determination of the classical molar mass parameters M(W), M(N), and M(P). It
      can be used for the determination of molar mass distributions of homopolymers and
      copolymers. The main advantage of SEC-NMR of copolymers is the possibility of
      detecting each monomer unit simultaneously with NMR as a quantitative
      concentration detector. Therefore, it is possible to provide the chemical
      compositions of copolymers at any elution volume without calibrations. In this
      respect, a new method will be presented for getting correct signal quantities of
      onflow data with sufficient NMR sensitivities. As the consequence, the chemical
      composition of copolymers can be correctly quantified under typical
      chromatographic conditions with respect to sample concentration and flow rate.
      Finally, the molar mass calibrations of the copolymers can be easily adjusted
      according to their chemical compositions. The methods were applied to polystyrene
      b-poly(methyl methacrylate) block copolymers of different molar masses. The
      results of the molar mass distributions and the chemical composition
      distributions obtained by SEC-NMR are in very good agreement with the complex SEC
      multidetector analysis.

PMID- 20809562
TI  - Combining SELEX screening and rational design to develop light-up fluorophore-RNA
      aptamer pairs for RNA tagging.
AB  - We report here a new small molecule fluorogen and RNA aptamer pair for RNA
      labeling. The small-molecule fluorogen is designed on the basis of fluorescently
      quenched sulforhodamine dye. The SELEX (Systematic Evolution of Ligands by
      EXponential enrichment) procedure and fluorescence screening in E. coli have been
      applied to discover the aptamer that can specifically activate the fluorogen with
      micromolar binding affinity. The systematic mutation and truncation study on the
      aptamer structure determined the minimum binding domain of the aptamer. A series
      of rationally modified fluorogen analogues have been made to probe the
      interacting groups of fluorogen with the aptamer. These results led to the design
      of a much improved fluorogen ASR 7 that displayed a 33-fold increase in the
      binding affinity for the selected aptamer in comparison to the original ASR 1 and
      an 88-fold increase in the fluorescence emission after the aptamer binding. This
      study demonstrates the value of combining in vitro SELEX and E. coli fluorescence
      screening with rational modifications in discovering and optimizing new fluorogen
      RNA aptamer labeling pairs.

PMID- 20809565
TI  - Enzymatic AND logic gates operated under conditions characteristic of biomedical
      applications.
AB  - Experimental and theoretical analyses of the lactate dehydrogenase and
      glutathione reductase based enzymatic AND logic gates in which the enzymes and
      their substrates serve as logic inputs are performed. These two systems are
      examples of the novel, previously unexplored class of biochemical logic gates
      that illustrate potential biomedical applications of biochemical logic. They are
      characterized by input concentrations at logic 0 and 1 states corresponding to
      normal and pathophysiological conditions. Our analysis shows that the logic gates
      under investigation have similar noise characteristics. Both significantly
      amplify random noise present in inputs; however, we establish that for realistic
      widths of the input noise distributions, it is still possible to differentiate
      between the logic 0 and 1 states of the output. This indicates that reliable
      detection of pathophysiological conditions is indeed possible with such enzyme
      logic systems.

PMID- 20809566
TI  - Evaluation of factors affecting stakeholder risk perception of contaminated
      sediment disposal in Oslo harbor.
AB  - The management of environmental pollution has changed considerably since the
      growth of environmental awareness in the late 1960s. The general increased
      environmental concern and involvement of stakeholders in today's environmental
      issues may enhance the need to consider risk in a much broader social context
      rather than just as an estimate of ecological hazard. Risk perception and the
      constructs and images of risks held by stakeholders and society are important
      items to address in the management of environmental projects, including the
      management of contaminated sediments. Here we present a retrospective case study
      that evaluates factors affecting stakeholder risk perception of contaminated
      sediment disposal that occurred during a remediation project in Oslo harbor,
      Norway. The choice to dispose dredged contaminated sediments in a confined
      aquatic disposal (CAD) site rather than at a land disposal site has received a
      lot of societal attention, attracted large media coverage, and caused many public
      discussions. A mixed method approach is used to investigate how risk perceptive
      affective factors (PAF), socio-demographic aspects, and participatory aspects
      have influenced the various stakeholders' preferences for the two different
      disposal options. Risk perceptive factors such as transparency in the decision
      making process and controllability of the disposal options have been identified
      as important for risk perception. The results of the study also support the view
      that there is no sharp distinction in risk perception between experts and other
      parties and emphasizes the importance of addressing risk perceptive affective
      factors in similar environmental decision-making processes. Indeed, PAFs such as
      transparency, openness, and information are fundamental to address in sensitive
      environmental decisions, such as sediment disposal alternatives, in order to
      progress to more technical questions such as the controllability and safety.

PMID- 20809567
TI  - A ditetrylyne as a pi-electron donor: synthesis and characterization of
      [AgAr'GeGeAr'](+)SbF6(-) and [Ag2Ar'GeGe(F)Ar'](+)SbF6(-) (Ar' = C6H3-2,6(C6H3
      2,6-Pr(i)2)2).
AB  - The reaction of a digermyne Ar'GeGeAr' (Ar' = C(6)H(3)-2,6-(C(6)H(3)-2,6
      Pr(i)(2))(2)) with AgSbF(6) at -40  degrees C forms the complex
      (AgAr'GeGeAr')(+)SbF(6)(-), which provides the first example of a heavier group
      14 element alkyne analogue behaving as a pi donor to a transition metal. The
      cation (AgAr'GeGeAr')(+) is best described as a hybrid of a pi-complex and a
      sigma-metallacyclopropene structure.

PMID- 20809568
TI  - Characterization of nucleosides and nucleobases in fruits of Ziziphus jujuba by
      UPLC-DAD-MS.
AB  - The fruit of Ziziphus jujuba , named dazao in Chinese, has been utilized as food
      as well as crude drugs in China for thousands of years. To explore the profiles
      of the nucleosides and nucleobases in this fruit, an ultraperformance liquid
      chromatograph coupled with a photodiode array detector and electrospray
      ionization-mass spectrometer method (UPLC-DAD-MS) has been established and
      validated in this paper. The validated method was successfully applied for the
      simultaneous characterization and quantitation of 9 nucleosides and nucleobases
      in 49 dazao samples, which comprised 43 cultivars from 26 cultivation regions.
      Furthermore, principal component analysis (PCA) was performed to classify the
      samples on the basis of the contents of the nine analyzed compounds. The results
      showed that almost all of these dazao samples were rich in nucleosides and
      nucleobases, although their contents were obviously various, and the proposed
      method could serve as a prerequisite for quality control of jujube products.

PMID- 20809569
TI  - Fluorinated diaminocyclopentanes as chiral sensitive NMR probes of RNA structure.
AB  - The supramolecular chiral recognition between rac-2a and several structured RNA
      leads to a distinct (19)F NMR signal splitting. The (19)F NMR analysis of the
      diastereomeric pairs formed upon binding of this racemic probe delivers a
      topological footprint of the RNA. This phenomenon can be exploited to investigate
      dynamic events involving structural equilibria, as demonstrated in a melting
      experiment. This work provides a proof of concept that small fluorinated moderate
      binders can act as external probes of RNA structures.

PMID- 20809570
TI  - Size-dependent oxygen activation efficiency over Pd(n)/TiO2(110) for the CO
      oxidation reaction.
AB  - The dissociative binding efficiency of oxygen over Pd(n)/TiO(2)(110) (n = 4, 7,
      10, 20) has been measured using temperature programmed reaction (TPR) mass
      spectrometry and X-ray photoemission spectroscopy (XPS) following exposure to
      O(2) with varying doses and dose temperatures. Experiments were carried out
      following two different O(2) exposures at 400 K (10 L and 50 L) and for 10 L of
      O(2) exposure at varying temperatures (T(surf) = 200, 300, and 400 K). During TPR
      taken after sequential O(2) and CO (5 L at 180 K) exposures, unreacted CO is
      found to desorb in three features at T(desorb) ~ 150, 200, and 430 K, while CO(2)
      is observed to desorb between 170 and 450 K. We show that Pd(20) has
      exceptionally high efficiency for oxygen activation, compared to other cluster
      sizes. As a consequence, its activity becomes limited by competitive CO binding
      at low O(2) exposures, while other Pd(n) sizes are still limited by inefficient
      O(2) activation. This difference in mechanism can ultimately be related back to
      differences in electronic properties, thus making this question one that is
      interesting from the theoretical perspective. We also demonstrate a correlation
      between one of the two CO binding sites and CO(2) production, suggesting that
      only CO in that site is reactive.

PMID- 20809571
TI  - Functionalized nanostructures: redox-active porphyrin anchors for supramolecular
      DNA assemblies.
AB  - We have synthesized and studied a supramolecular system comprising a 39-mer DNA
      with porphyrin-modified thymidine nucleosides anchored to the surface of large
      unilamellar vesicles (liposomes). Liposome porphyrin binding characteristics,
      such as orientation, strength, homogeneity, and binding site size, was
      determined, suggesting that the porphyrin is well suited as a photophysical and
      redox-active lipid anchor, in comparison to the inert cholesterol anchor commonly
      used today. Furthermore, the binding characteristics and hybridization
      capabilities were studied as a function of anchor size and number of anchoring
      points, properties that are of importance for our future plans to use the
      addressability of these redox-active nodes in larger DNA-based nanoconstructs.
      Electron transfer from photoexcited porphyrin to a lipophilic benzoquinone
      residing in the lipid membrane was characterized by steady-state and time
      resolved fluorescence and verified by femtosecond transient absorption.

PMID- 20809572
TI  - Temperature and light induced bistability in a Co3[Os(CN)6]2 6 H2O Prussian blue
      analog.
AB  - To expand the field of new cyanide materials of the 5d elements, we incorporated
      the [Os(CN)(6)](3-) anion into PB architectures in combination with the Co(II)
      cation. Herein, we report the first example of a photomagnetic PB analog
      containing Os(III) ions. In a similar vein as the prototypical CoFe PB analogs,
      this compound exhibits a wide variety of properties including Charge Transfer
      Induced Spin Transition (CTIST), Temperature Induced Excited Spin State Trapping
      (TIESST), and magnetic ordering.

PMID- 20809573
TI  - Oxidative template for conducting polymer nanoclips.
AB  - Bulk quantities of electronic conducting polymers such as polyaniline,
      polypyrrole, and poly(3,4-ethylenedioxythiophene), having an unusual 2D nanoclip
      like morphology is described using a general oxidative template assembly route
      which is orchestrated by an insoluble complex formed between an anionic oxidant
      (S(2)O(8)(2-)) and a cationic surfactant.

PMID- 20809574
TI  - Observing iridium oxide (IrO(x)) single nanoparticle collisions at
      ultramicroelectrodes.
AB  - We describe the electrochemical detection of single iridium oxide nanoparticle
      (IrO(x) NP) collisions on a NaBH(4)-treated Pt ultramicroelectrode (UME). We
      observe single NP events through the enhanced current by electrocatalytic water
      oxidation, when IrO(x) contacts the electrode and transiently sticks to it. The
      overall current transient consists of repeated current spikes that return to the
      background level, superimposed on a current decay, rather than the staircase
      response seen where an NP sticks on the UME. Here each event produces a unique
      current spike (or "blip"). The frequency of the spikes was directly proportional
      to the particle concentration, and the peak current increased with the applied
      potential. The observed current is very sensitive to the material and surface
      state of the measuring electrode; a NaBH(4)-treated Pt UME was important in
      obtaining reproducible results.

PMID- 20809575
TI  - A three-dimensional coculture of enterocytes, monocytes and dendritic cells to
      model inflamed intestinal mucosa in vitro.
AB  - While epithelial cell culture models (e.g., Caco-2 cell line) are widely used to
      assess the absorption of drug molecules across healthy intestinal mucosa, there
      are no suitable in vitro models of the intestinal barrier in the state of
      inflammation. Thus development of novel drugs and formulations for the treatment
      of inflammatory bowel disease is largely bound to animal models. We here report
      on the development of a complex in vitro model of the inflamed intestinal mucosa,
      starting with the selection of suitable enterocyte cell line and proinflammatory
      stimulus and progressing to the setup and characterization of a three-dimensional
      coculture of human intestinal epithelial cells and immunocompetent macrophages
      and dendritic cells. In the 3D setup, controlled inflammation can be induced
      allowing the mimicking of pathophysiological changes occurring in vivo in the
      inflamed intestine. Different combinations of proinflammatory stimuli
      (lipopolysaccharides from Escherichia coli and Salmonella typhimurium,
      interleukin-1beta, interferon-gamma) and intestinal epithelial cell lines (Caco
      2, HT-29, T84) were evaluated, and only Caco-2 cells were responsive to
      stimulation, with interleukin-1beta being the strongest stimulator. Caco-2 cells
      responded to the proinflammatory stimulus with a moderate upregulation of
      proinflammatory markers and a slight, but significant, decrease (20%) of
      transepithelial electrical resistance (TEER) indicating changes in the epithelial
      barrier properties. Setting up the coculture model, macrophages and dendritic
      cells derived from periphery blood monocytes were embedded in a collagen layer on
      a Transwell filter insert and Caco-2 cells were seeded atop. Even in the presence
      of immunocompetent cells Caco-2 cells formed a tight monolayer. Addition of IL
      1beta increased inflammatory cytokine response more strongly compared to Caco-2
      single culture and stimulated immunocompetent cells proved to be highly active in
      sampling apically applied nanoparticles. Thus the 3D coculture provides
      additional complexity and information compared to the stimulated single cell
      model. The coculture system may serve as a valuable tool for developing drugs and
      formulations for the treatment of inflammatory bowel diseases, as well as for
      studying the interaction of xenobiotics and nanoparticles with the intestinal
      epithelial barrier in the state of inflammation.

PMID- 20809576
TI  - Effect of ionic strength on surface-selective patch binding-induced phase
      separation and coacervation in similarly charged gelatin-agar molecular systems.
AB  - Coacervate is defined as a polymer-rich dense phase, which remains in
      thermodynamic equilibrium with its low concentrated phase called the supernatant.
      The effect of ionic strength (I = 0-0.1 M NaCl) on the mechanism of surface patch
      binding-induced protein-polysaccharide interaction leading to complex
      coacervation, between agar (a polyanionic polysaccharide) and gelatin B (a
      polyampholyte protein), both having similar net charge, at a particular mixing
      ratio, [gelatin]/[agar] = 1, was studied at various temperatures (20-40  degrees
      C). The coacervation transition was probed by turbidity and zeta-potential
      measurements. The intermolecular association had the signature of surface
      selective binding, and a model calculation could explain the potential energy of
      interactions operative in such processes. The thermo-mechanical features of the
      coacervates were found to be strongly dependent on ionic strength, which has been
      interpreted as originating from formation of salt-bridges between the
      biopolymers. The microstructure of the coacervate materials was analyzed using
      rheology and small angle neutron scattering (SANS) techniques, which probed the
      heterogeneity prevailing in the system that had characteristic length in the
      range 1.3-2.0 nm, and the same data yielded the correlation length of
      concentration fluctuations, which was estimated to lay in the range 2.4-4 nm. It
      is concluded that the coacervation transition driven by surface-selective binding
      is not influenced by the ionic strength of the solution, but the mobile ions
      participate in the structural organization of the interacting polyions in the
      coacervate.

PMID- 20809577
TI  - Water diffusion behaviors and transportation properties in transmembrane cyclic
      hexa-, octa- and decapeptide nanotubes.
AB  - Molecular dynamics simulations have been performed on three transmembrane cyclic
      peptide nanotubes, i.e., 8 * (WL)(n=3,4,5)/POPE (with uniform lengths but various
      radii) to investigate the radial dependences of the water-chain structures,
      diffusions, and transportation properties. The diffusions of individual water
      molecules and collective coordinates of all the channel-water in the three
      systems are certified as unbiased Brownian motions. From the very good linear
      relationships between MSDs and time intervals, the diffusion coefficients and
      transportation permeabilities have been deduced efficiently. Under the
      hydrostatic pressure differences across the membrane, a net unidirectional water
      flow rose up, and the osmotic permeabilities were determined. The ratios of the
      osmotic and diffusion permeabilities (p(f)/p(d)) were examined for all the three
      channels.

PMID- 20809578
TI  - Reactions of boron amidinates with CO2 and CO and other small molecules.
AB  - Reaction of Piers' borane, HB(C(6)F(5))(2), with either tert-butyl or isopropyl
      carbodiimide cleanly affords the boron amidinates HC(RN)(2)B(C(6)F(5))(2) [R =
      iPr (1), tBu (2)]. These species undergo a variety of insertion reactions. For
      example, treatment of 1 with CO(2) or excess carbodiimide gives
      HC(iPrN)(2)(CO(2))B(C(6)F(5))(2) (3) or HC(iPrN)(2)C(iPrN)(2)B(C(6)F(5))(2) (4),
      respectively. Similarly, exposure of 1 or 2 to 1 atm CO gives
      HC(RN)(2)(CO)B(C(6)F(5))(2) [R = iPr (5), tBu (6)], while reaction of 1 with
      CNtBu gives HC(RN)(2)(CNtBu)B(C(6)F(5))(2) [R = iPr (7), tBu (8)]. Compounds 1
      and 2 also react with benzaldehyde, resulting in the formation of
      HC(RN)(2)(PhHCO)B(C(6)F(5))(2) [R = iPr (9), tBu (10)]. Compound 1 also reacts
      with MeCN to give HC(iPrN)(2)(MeCN)B(C(6)F(5))(2) (11) and effects heterolytic C
      H cleavage to afford HC(iPrN)(iPrNH)(PhCC)B(C(6)F(5))(2) (12). In contrast, the
      species PhC(iPrN)(2)B(C(6)F(5))(2) (14) derived from PhC(iPrN)(2)BCl(2) (13)
      failed to react with any of the above substrates. These data, in addition to the
      isolation of HC(iPrN)(2)(C(6)F(4))BF(C(6)F(5)) (15), the product of thermolysis
      of 1, provide further support for the notion that the transient "open-chain" form
      of these amidinates is present in solution.

PMID- 20809579
TI  - N-heterocyclic carbene-catalyzed conjugate additions of alcohols.
AB  - An efficient intermolecular conjugate addition of alcohols to activated alkenes
      catalyzed by N-heterocyclic carbenes has been developed. With 5 mol % of the free
      carbene derived from IMes.HCl, unsaturated ketones and esters are competent
      substrates, and a variety of primary and secondary alcohols can be employed as
      the nucleophile. No oligomerization is observed under these mild conditions for
      effective hydroalkoxylation. In addition to reactions with activated alkenes,
      IMes catalyzes the formation of vinyl ethers through the 1,4-addition of alcohols
      to ynones and promotes tandem conjugate addition/Michael cascade reactions.
      Preliminary data support a Bronsted base mechanism with the free carbene.

PMID- 20809580
TI  - Exploring the ground and excited states structural diversity of levosimendan, a
      cardiovascular calcium sensitizer.
AB  - Exploring the relationship between the structure and dynamics of a molecular
      system is fundamental to a better understanding of its function. Here, we report
      on studies of femtosecond dynamics of the most stable molecular structures of a
      cardiovascular drug, levosimendan (LSM), in water at three different pHs, in
      chemical (beta-cyclodextrin, beta-CD) and biological (human serum albumin
      protein, HSA) nanocavities, and in two organic solvents with different
      viscosities. In the used organic solvents, the structural dynamics, ranging from
      50 fs to 3 ps, depends on the viscosity of the solvent, reflecting the
      involvement of a twisting motion in the excited molecule. In water solutions at
      pH 3 and 5, the excited neutral form is decaying in a time of ~0.4 ps, undergoing
      an ultrafast (<50 fs) intramolecular charge transfer (ICT) to generate charge
      transfer species decaying in ~1 ps. In neutral (pH 7) and alkaline water (pH 12),
      the LSM is present in its anion structure at the ground state. In these media,
      the experiments reveal, in addition to the ultrafast decay of the anionic
      structure (1.3 ps), the formation of an ICT state having (n, pi*) character,
      produced in ~0.3 ps and decaying in ~0.5 ps. Encapsulation by beta-CD and HSA
      protein leads to a 1:1 stoichiometry complex, which shows longer decaying times
      (4 and 7 ps, respectively) of the caged anionic forms due to the nanoconfinement.
      Our results show a structural diversity of the LSM dynamics, reflecting its
      intimate interaction with its surrounding. We believe that the reported findings
      and the related discussion and conclusions bring new knowledge for a better
      understanding of the molecular activity of this drug, taking into account its
      rich structural dynamics. Furthermore, the results might be relevant for a better
      drug design and nanodelivery involving CDs and proteins.

PMID- 20809581
TI  - Effect of structure and size on the electrical properties of nanocrystalline WO3
      films.
AB  - Nanocrystalline WO3 films were grown by reactive magnetron sputter-deposition by
      varying the substrate temperature in the range of 303(RT)-673 K. The structure
      and electrical transport properties of WO3 films were evaluated using X-ray
      diffraction and dc electrical conductivity measurements. The effect of
      ultramicrostructure and grain-size was significant on the electrical properties
      of WO3 films. DC conductivity variation of the WO3 films measured in the
      temperature range of 120-300 K reveals their semiconducting nature. The
      temperature dependent electrical conductivity curves exhibit two distinct regions
      indicative of two different types of electrical transport mechanisms. Analysis of
      the conductivity indicates that the small polaron and variable-range-hopping
      mechanisms are operative in 180-300 K and 120-180 K temperature regions,
      respectively. The density of localized states at the Fermi level, N(EF), has been
      calculated and it was found to be ~1*10(19) eV(-1) cm(-3) for all the films.

PMID- 20809582
TI  - Determination of spiropyran cytotoxicity by high content screening and analysis
      for safe application in bionanosensing.
AB  - The in vitro toxic response of spiropyrans in cellular models has not been
      previously addressed, despite the fact that such photoswitchable molecules have
      shown great potential as versatile and tunable components for bionanodevices and
      imaging agents. In this study, we examine the cytotoxic effects of a spiropyran,
      namely, 8-methoxy-6-nitro-BIPS (1',3'-dihydro-1'-ethanol-3',3'-dimethyl-8-methoxy
      6-nitro-spiro(2H-1-benzopyran-2,2'-(2H)-indole) [1], in three cultured cellular
      models (THP-1, AGS, and A549 cell lines) by High Content Screening and Analysis
      (HCSA) and by enzyme-linked immunosorbent (ELISA) assays (Interleukin-6 and Tumor
      Necrosis Factor-alpha). The HCSA results show that low concentrations of 8
      methoxy-6-nitro-BIPS (10(-6), 10(-8), and 10(-9) M) do not induce any cytotoxic
      response after 24 and 72 h exposure time, while at the highest concentrations
      (10(-3)and 10(-4) M) the exposure time becomes a critical parameter of the toxic
      response. The cell viability is reduced by 60% for THP-1 cells, 50% for AGS
      cells, and 40% for A549 cells at a spiropyran concentration of 10(-3) M after 24
      h incubation, whereas at 72 h, the cell loss increases above 90%. Interestingly,
      at 10(-4) M no significant cytotoxic response is registered after 24 h exposure,
      where contrarily cytotoxicity is verified after 72 h. Our ELISA results show that
      consistently with the HCSA analysis a robust inflammatory response is present at
      10(-3) M after 24 h exposure and at 10(-3) M and 10(-4) M after 72 h, in all
      three cell lines investigated.

PMID- 20809583
TI  - Role of solvent dynamics in ultrafast photoinduced proton-coupled electron
      transfer reactions in solution.
AB  - A theoretical formulation for modeling photoinduced nonequilibrium proton-coupled
      electron transfer (PCET) reactions in solution is presented. In this formulation,
      the PCET system is described by donor and acceptor electron-proton vibronic free
      energy surfaces that depend on a single collective solvent coordinate. Dielectric
      continuum theory is used to obtain a generalized Langevin equation of motion for
      this collective solvent coordinate. The terms in this equation depend on the
      solvent properties, such as the dielectric constants, relaxation time, and
      molecular moment of inertia, as well as the solute properties characterizing the
      vibronic surfaces. The ultrafast dynamics following photoexcitation is simulated
      using a surface hopping method in conjunction with the Langevin equation of
      motion. This methodology is used to examine a series of model photoinduced PCET
      systems, where the initial nonequilibrium state is prepared by vertical
      photoexcitation from the ground electronic state to the donor electronic state.
      Analysis of the dynamical trajectories provides insight into the interplay
      between the solvent dynamics and the electron-proton transfer for these types of
      processes. In addition, these model studies illustrate how the coupling between
      the electron-proton transfer and the solvent dynamics can be tuned by altering
      the solute and solvent properties.

PMID- 20809584
TI  - Enantioselective 1,6-conjugate addition to cyclic dienones catalyzed by the Cu
      DiPPAM complex.
AB  - In the presence of a Cu/DiPPAM catalytic system, various diorganozinc reagents
      realize 1,6-asymmetric conjugate addition on various cyclic five- and six
      membered cyclic dienones, with complete regioselectivity and high ee's (93-99%).

PMID- 20809585
TI  - Can a carbon nanotube pierce through a phospholipid bilayer?
AB  - Great efficiency to penetrate into living cells is attributed to carbon nanotubes
      due to a number of direct and indirect observations of carbon nanotubes inside
      the cells. However, a direct evidence of physical translocation of nanotubes
      through phospholipid bilayers and the exact microscopic mechanism of their
      penetration into cells are still lacking. In order to test one of the inferred
      translocation mechanisms, namely the spontaneous piercing through the membrane
      induced only by thermal motion, we calculate the energy cost associated with the
      insertion of a carbon nanotube into a model phospholipid bilayer using the single
      chain mean field theory, which is particularly suitable for the accurate
      measurements of equilibrium free energies. We find that the energy cost of the
      bilayer rupture is quite high compared to that of the energy of thermal motion.
      This conclusion may indirectly support other energy-dependent translocation
      mechanisms, such as, for example, endocytosis.

PMID- 20809586
TI  - Polarization caging in diffusion-controlled electron transfer reactions in
      solution.
AB  - In some bimolecular diffusion-controlled electron transfer (ET) reactions such as
      ion recombination (IR), both solvent polarization relaxation and the mutual
      diffusion of the reacting ion pair may determine the rate and even the yield of
      the reaction. However, a full treatment with these two reaction coordinates is a
      challenging task and has been left mostly unsolved. In this work, we address this
      problem by developing a dynamic theory by combining the ideas from ET reaction
      literature and barrierless chemical reactions. Two-dimensional coupled
      Smoluchowski equations are employed to compute the time evolution of joint
      probability distribution for the reactant (P((1))(X,R,t)) and the product
      (P((2))(X,R,t)), where X, as is usual in ET reactions, describes the solvent
      polarization coordinate and R is the distance between the reacting ion pair. The
      reaction is described by a reaction line (sink) which is a function of X and R
      obtained by imposing a condition of equal energy on the initial and final states
      of a reacting ion pair. The resulting two-dimensional coupled equations of motion
      have been solved numerically using an alternate direction implicit (ADI) scheme
      (Peaceman and Rachford, J. Soc. Ind. Appl. Math. 1955, 3, 28). The results reveal
      interesting interplay between polarization relaxation and translational dynamics.
      The following new results have been obtained. (i) For solvents with slow
      longitudinal polarization relaxation, the escape probability decreases
      drastically as the polarization relaxation time increases. We attribute this to
      caging by polarization of the surrounding solvent. As expected, for the solvents
      having fast polarization relaxation, the escape probability is independent of the
      polarization relaxation time. (ii) In the slow relaxation limit, there is a
      significant dependence of escape probability and average rate on the initial
      solvent polarization, again displaying the effects of polarization caging. Escape
      probability increases, and the average rate decreases on increasing the initial
      polarization. Again, in the fast polarization relaxation limit, there is no
      effect of initial polarization on the escape probability and the average rate of
      IR. (iii) For normal and barrierless regions the dependence of escape probability
      and the rate of IR on initial polarization is stronger than in the inverted
      region. (iv) Because of the involvement of dynamics along R coordinate, the
      asymmetrical parabolic (that is, non-Marcus) energy gap dependence of the rate is
      observed.

PMID- 20809587
TI  - Poisoning people and wildlife with lead ammunition: time to stop.

PMID- 20809588
TI  - The need for simultaneous evaluation of ecosystem services and land use change.

PMID- 20809589
TI  - Role of photodegradation in the fate of fluorescent whitening agents (FWAs) in
      lacustrine environments.
AB  - To understand the behavior of fluorescent whitening agents (FWAs) in a lake
      environment, we measured the quantities of two FWAs, DSBP, and DAS1, in water
      samples collected monthly from six depths of the water column, in sediment trap
      sample, and a sediment core sample from Lake Biwa, the largest lake in Japan, and
      in sewage, effluent, and river water in the lake's catchment. We conducted a
      sunlight exposure experiment and developed a method to estimate the degree of
      photodegradation by using DSBP/DAS1 ratio in environmental samples. The observed
      seasonal pattern of the vertical distributions of the FWAs in the water column
      can be explained by stratification of the water, photodegradation in the euphotic
      zone, the subsurface loading of river water, and their seasonal changes. The
      DSBP/DAS1 ratio was much lower in the lake water (0.12-0.52) than in sewage (6.4
      +/- 1.1), indicating intensive photodegradation in rivers and the lake. A mass
      balance calculation and DSBP/DAS1 ratio demonstrated that ~95% of DSBP and ~55%
      of DAS1 supplied in sewage were photodegraded in inflowing rivers and the lake,
      and that sedimentation to the lake bottom is insignificant for DSBP and ~35% for
      DAS1. More intensive photodegradation of FWAs, especially more photodegradable
      DSBP, in Lake Biwa than in Greifensee, a lake in Switzerland, was suggested,
      attributable to the longer residence time of water in and the larger size of Lake
      Biwa. These results demonstrate that photodegradation is important to the fate of
      FWAs in lacustrine environments, and that FWAs and the DSBP/DAS1 ratio are useful
      markers for understanding the role of direct photodegradation in the behavior of
      water-soluble chemicals in aquatic environments.

PMID- 20809590
TI  - Reaction of N-acylhomoserine lactones with hydroxyl radicals: rates, products,
      and effects on signaling activity.
AB  - Chemical communication in bacteria, sometimes called quorum sensing, is a
      fundamental microbial process that is based on the exchange of molecular signals
      between cells. The signaling molecules involved in this process are
      thermodynamically unstable in some environments and their degradation affects
      microbial communication. This work reports the oxidation of a series of
      substituted N-acylhomoserine lactones (AHLs, a class of quorum sensing signals)
      by hydroxyl radicals. The corresponding bimolecular rate constants were obtained
      and correlated positively with the length of the acyl side chain (C, in numbers
      of carbon atoms) ranging from 2.4 * 10(9) M(-1) s(-1) to 9.4 * 10(9) M(-1) s(-1)
      (C4- to C10-AHL), 2.4 * 10(8) M(-1) s(-1) for 3-oxo C6-AHL, and 2.94 * 10(9) M(
      1) s(-1) for 3-oxo C8-AHL. Liquid chromatography-mass spectrometric techniques
      were applied to qualify the identity and quantify the yields of the hydroxyl
      radical oxidation products of C6-AHL (aldo, keto, and hydroxylated C6-analogues
      identified). The biological activity of C6-AHL and associated products was
      determined using the Vibrio harveyi bioluminescence bioassay. Oxidation resulted
      in a net increase in assay response indexed against the starting AHL. This result
      suggested that the application of HO* based technologies such as advanced
      oxidation processes for biofilm control may result in unintended quorum sensing
      responses by microbial communities.

PMID- 20809591
TI  - Evolution of equilibrium Pickering emulsions--a matter of time scales.
AB  - A new class of equilibrium solid-stabilized oil-in-water emulsions harbors a
      competition of two processes on disparate time scales that affect the equilibrium
      droplet size in opposing ways. The aim of this work is to elucidate the molecular
      origins of these two time scales and demonstrate their effects on the evolution
      of the emulsion droplet size. First, spontaneous emulsification into particle
      covered droplets occurs through in situ generation of surface-active molecules by
      hydrolysis of molecules of the oil phase. We show that surface tensions of the
      oil-water interfaces in the absence of stabilizing colloidal particles are
      connected to the concentration of these surface-active molecules, and hence also
      to the equilibrium droplet size in the presence of colloids. As a consequence,
      the hydrolysis process sets the time scale of formation of these solid-stabilized
      emulsions. A second time scale is governing the ultimate fate of the solid
      stabilized equilibrium emulsions: by condensation of the in situ generated
      amphiphilic molecules onto the colloidal particles, their wetting properties
      change, leading to a gradual transfer from the aqueous to the oil phase via
      growth of the emulsion droplets. This migration is observed macroscopically by a
      color change of the water and oil phases, as well as by electron microscopy after
      polymerization of the oil phase in a phase separated sample. Surprisingly, the
      relative oil volume sets the time scale of particle transfer. Phase separation
      into an aqueous phase and an oil phase containing colloidal particles is
      influenced by sedimentation of the emulsion droplets. The two processes of
      formation of surface-active molecules through hydrolysis and condensation thereof
      on the colloidal surface have an opposite influence on the droplet size. By their
      interplay, a dynamic equilibrium is created where the droplet size always adjusts
      to the thermodynamically stable state.

PMID- 20809593
TI  - Nonadiabatic dynamics on the two coupled electronic PESs: the H+ + O2 system.
AB  - Multistate adiabatic and diabatic PESs were computed for the H+ + O2 collision
      system in Jacobi coordinates, (R,r,gamma) using the cc-pVTZ basis set and the ic
      MRCI level of theory. In addition, all possible interaction potentials and
      nonadiabatic coupling matrix elements among those different electronic states
      were also computed. Comparisons with earlier computed interaction potentials were
      made wherever possible, and the differences between them is attributed to the
      multistate diabatization and the chosen level of theory and basis set. Focusing
      our attention on the ground-state (GS) and the first excited-state (ES) PES,
      quantum dynamics were performed using the 2 * 2 diabatic potential submatrix
      obtained from the multistate (four) diabatic potential matrix within the VCC
      RIOSA scheme at two experimentally reported collision energies, E(cm) = 9.5 and
      23 eV. The scattering quantities were computed for two experimentally observed
      collision processes, namely, the inelastic vibrational excitation (IVE), H+ + O2
      (X3Sigmag(-),v = 0) -> H+ + O2 (X3Sigmag(-),v'), and the vibrational charge
      transfer (VCT), H+ + O2 (X3Sigmag(-),v = 0) -> H (2S) + O (X2Pig,v'').
      Comparisons were made with experimental results and found an overall improvement
      relative to the earlier computed results, and the discrepancies, if any, could be
      brought down to minimum by further modification in employed ab initio PESs and
      the interaction potential.

PMID- 20809592
TI  - Self-organization of 2-acylaminopyridines in the solid state and in solution.
AB  - Aggregation of 2-acylaminopyridines and their 6-methyl derivatives in chloroform
      solution was studied by (1)H, (13)C, and (15)N NMR spectroscopies. The results
      were compared with (13)C and (15)N CPMAS NMR and IR spectral as well as with X
      ray structural data. Intermolecular interactions in solution and in solid state
      were found to have a similar nature. Relatively strong N(amide)-H...N(pyridine)
      intermolecular hydrogen bonds enable dimerization to take place. Steric
      interactions in N-pivaloyl- and N-1-adamantylcarbonyl as well as that caused by
      the 6-methyl group hinder formation of the dimeric aggregates stabilized by the
      N(amide)-H...N(pyridine) intermolecular hydrogen bonds. In general, the DFT
      optimized geometries of the aggregates in chloroform solution are in agreement
      with the X-ray crystal structures. Wavenumbers of the stretching vibration band
      of the C?O group were also found indicative of the type of hydrogen bond present
      in the solid state.

PMID- 20809594
TI  - Selective and direct immobilization of cysteinyl biomolecules by electrochemical
      cleavage of azo linkage.
AB  - Controlled orientation and reserved activity of biomolecules, when site
      selectively immobilized in a highly integrated manner on a minimal time scale,
      are crucial in designing biosensors for the multiplex detection. Here, we
      describe a novel method for the orientation-controlled immobilization of
      biomolecules based on site-selective electrochemical activation of p
      hydroxyazobenzene self-assembled monolayer (SAM) followed by one-step coupling of
      cysteinyl biomolecules. The p-aminophenol, a product of reductive cleavage of p
      hydroxyazobenzene, was subsequently oxidized to yield p-quinoneimine which then
      conjugated with cysteinyl biomolecules through 1,4-Michael addition, thus
      obviating additional linker agents and the related time consumption. Using this
      method, we selectively activated the electrode surface and immobilized laminin
      peptide IKVAV, a neurite promoting motif. When we cultured hippocampal neurons on
      the electrode, the extended neurites were found only within the electrochemically
      activated area. Hence, the proposed method represents a new promising platform
      for the patterning of functional peptides, active proteins, and live cells.

PMID- 20809595
TI  - Efficient bioconjugation of protein capture agents to biosensor surfaces using
      aniline-catalyzed hydrazone ligation.
AB  - Aniline-catalyzed hydrazone ligation between surface-immobilized hydrazines and
      aldehyde-modified antibodies is shown to be an efficient method for attaching
      protein capture agents to model oxide-coated biosensor substrates. Silicon
      photonic microring resonators are used to directly evaluate the efficiency of
      this surface bioconjugate reaction at various pHs and in the presence or absence
      of aniline as a nucleophilic catalyst. It is found that aniline significantly
      increases the net antibody loading for surfaces functionalized over a pH range
      from 4.5 to 7.4, allowing derivatization of substrates with reduced incubation
      time and sample consumption. This increase in antibody loading directly results
      in more sensitive antigen detection when functionalized microrings are employed
      in a label-free immunoassay. Furthermore, these experiments also reveal an
      interesting pH-dependent noncovalent binding trend that plays an important role
      in dictating the amount of antibody attached onto the substrate, highlighting the
      competing contributions of the bioconjugate reaction rate and the dynamic
      interactions that control opportunities for a solution-phase biomolecule to react
      with a substrate-bound reagent.

PMID- 20809597
TI  - Lanthanide-based luminescent NanoGUMBOS.
AB  - Lanthanide photochemistry has been frequently studied for its high luminescence
      intensity, narrow emission band, and stable luminescent lifetime decay. In the
      work presented here, nanoparticles prepared using an aerosolization process were
      derived from europium-based GUMBOS (Group of Uniform Material Based on Organic
      Salts). These nanoparticles were characterized using electron microscopy, X-ray
      photoelectron spectroscopy (XPS), absorbance, and photoluminescence spectroscopy.
      An average diameter of 39.5 +/- 8.4 nm for our nanoparticles was estimated by use
      of electron microscopy. Absorbance, luminescence, and luminescence lifetime decay
      measurements indicate intense and steady luminescence, which suggests a multitude
      of possible applications for lanthanide-based GUMBOS, especially in sensory
      devices, OLEDs, and photovoltaic devices.

PMID- 20809596
TI  - Protein adducts as prospective biomarkers of nevirapine toxicity.
AB  - Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor used against
      human immunodeficiency virus type-1 (HIV-1), mostly to prevent mother-to-child
      HIV-1 transmission in developing countries. Despite its clinical efficacy, NVP
      administration is associated with a variety of toxic responses that include
      hepatotoxicity and skin rash. Although the reasons for the adverse effects of NVP
      administration are still unclear, increasing evidence supports the involvement of
      metabolic activation to reactive electrophiles. In particular, Phase II
      activation of the NVP metabolite 12-hydroxy-NVP is thought to mediate NVP binding
      to bionucleophiles, which may be at the onset of toxicity. In the present study,
      we investigated the nature and specific locations of the covalent adducts
      produced in human serum albumin and human hemoglobin by reaction in vitro with
      the synthetic model electrophile 12-mesyloxy-NVP, used as a surrogate for the
      Phase II metabolite 12-sulfoxy-NVP. Multiple sites of modification were
      identified by two different mass spectrometry-based methodologies, liquid
      chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS)
      and matrix-assisted laser desorption ionization tandem mass spectrometry (MALDI
      TOF-TOF-MS). These two distinct methodologies, which in some instances afforded
      complementary information, allowed the identification of multiple adducts
      involving cysteine, lysine, tryptophan, histidine, serine, and the N-terminal
      valine of hemoglobin. Tryptophan, which is not a common site of covalent protein
      modification, was the NVP-modified amino acid residue detected in the two
      proteins and consistently identified by both LC-ESI-MS/MS and MALDI-TOF-TOF-MS.
      The propensity of tryptophan to react with the NVP-derived electrophile is
      further emphasized by the fact that human serum albumin possesses a single
      tryptophan residue, which suggests a remarkable selectivity that may be useful
      for biomonitoring purposes. Likewise, the NVP adduct with the terminal valine of
      hemoglobin, detected by LC-ESI-MS/MS after N-alkyl Edman degradation, appears as
      an easily assessed marker of NVP binding to proteins. Our results demonstrate the
      merits and complementarity of the two MS-based methodologies for the
      characterization of protein binding by NVP and suggest a series of plausible
      biomarkers of NVP toxicity that should be useful in the monitoring of toxicity
      effects in patients administered NVP.

PMID- 20809598
TI  - Pretransitional orientational ordering of a calamitic liquid crystal by helical
      nanofilaments of a bent-core mesogen.
AB  - Mixtures of 8CB (a calamitic mesogen) and NOBOW (P-9-O-PIMB, a bent-core mesogen)
      have been investigated using differential scanning calorimetry, nuclear magnetic
      resonance spectroscopy, and freeze fracture transmission electron microscopy. On
      cooling the isotropic mixture, the NOBOW component phase separates, forming a
      dilute, random network of helical nanofilaments in the B4 phase with isotropic
      8CB material filling the interstitial volume. At lower temperature, but still far
      above the bulk isotropic-nematic transition of pure 8CB, a significant fraction
      of the 8CB becomes prealigned on the filament surfaces. We propose that this
      pretransitional ordering is induced by short-range interactions of the polar 8CB
      molecules with the NOBOW filaments, leading to the formation of an adsorbed film
      of orientationally frozen 8CB around each filament.

PMID- 20809599
TI  - Effects of surface chemistry on cytotoxicity, genotoxicity, and the generation of
      reactive oxygen species induced by ZnO nanoparticles.
AB  - The relationship between the toxicity of zinc oxide (ZnO) nanoparticles (NPs) and
      their surface chemistry was investigated. Cytotoxicity, genotoxicity, and the
      ability to generate reactive oxygen species (ROS) were assessed for well
      characterized ZnO NPs whose surface chemistry was varied from its pristine state
      by coating with oleic acid (OA), poly(methacrylic acid) (PMAA), or components
      adsorbed from cell culture medium (medium-soaked). It was found that uncoated NPs
      showed ROS accumulation and diminished cell viability whereas all tested surface
      coatings assisted in reducing ROS production and cytotoxicity. The ability of
      coatings to reduce the cytotoxicity of ZnO NPs was ranked in the following order:
      medium-soaked ~ PMAA > OA. However, PMAA-coated ZnO had significant genotoxicity
      compared to uncoated ZnO and the other coated NPs, highlighting the need to
      investigate thoroughly the effects of NP surface modification on both
      cytotoxicity and genotoxicity assays. The lowest toxicity was achieved with a
      surface coating of components from a cell culture medium.

PMID- 20809600
TI  - Free volume theory applied to lateral diffusion in Langmuir monolayers: atomistic
      simulations for a protein-free model of lung surfactant.
AB  - We hereby present a study on lateral diffusion of lipids in Langmuir monolayers.
      We apply atomistic molecular dynamics simulations to a model system whose
      composition is consistent with protein-free lung surfactant. Our main focus is on
      the assessment of the validity of the free volume theory for lateral diffusion
      and on the interpretation of the cross-sectional area and activation energy
      parameters appearing in the theory. We find that the diffusion results can be
      fitted to the description given by the free volume theory, but the interpretation
      of its parameters is not straightforward. While the cross-sectional area appears
      to be related to the hard-core cross-sectional area of a lipid, its role in the
      lateral diffusion process is unclear. Also, the activation energy derived using
      the free volume theory is different from the activation energy found through
      Arrhenius analysis, and its physical interpretation remains elusive. Finally, we
      find that lipid diffusion does not occur via rapid single-particle "jumps".
      Instead, lipids move in a concerted manner as loosely defined transient clusters,
      as observed earlier for lipid bilayers.

PMID- 20809601
TI  - Effect of hydrocarbons on the morphology of synthesized niobium carbide
      nanoparticles.
AB  - Niobium carbide nanoparticles were synthesized by flowing methane, ethylene, or
      acetylene gas through a plasma generated from an arc discharge between two
      niobium electrodes. Varying methane, ethylene, and acetylene concentrations were
      employed in the studies to investigate their effects on niobium carbide
      nanoparticle morphology. Transmission electron microscopy (TEM), energy
      dispersive X-ray spectroscopy (EDS), and selected area diffraction pattern (SADP)
      were used to investigate the synthesized NbC nanoparticles, whereupon it was
      found that these nanoparticles adopt cubic morphology with methane gas, a mixture
      of cubes and cuboctahedron morphology with ethylene gas, and solely a
      cuboctahedron morphology with acetylene gas. The change in particle morphology
      might be attributed to either the ethylene and acetylene free radicals or the
      increase in carbon concentration effecting the relative growth rates of the {111}
      and {100} facets on a NbC seed crystal.

PMID- 20809602
TI  - Molecular thermodynamic modeling of specific ion effects on micellization of
      ionic surfactants.
AB  - Specific ion effects are ubiquitous in biological and colloidal systems. The
      addition of electrolytes to ionic surfactant solutions has pronounced effects on
      micellar properties, such as critical micelle concentration (cmc), micellar size,
      and shape. Ions play an important role in colloid stability and aggregation
      behavior of ionic surfactant solutions. Despite extensive experimental data,
      there is no well established molecular theory on specific ion effects. Published
      molecular thermodynamic theories for ionic surfactants do not properly account
      for ion-specific effects such as the inversion of the lyotropic series for the
      cmc of alkyl sulfates and carboxylates. In this work, we present a molecular
      thermodynamic theory for ionic surfactant solutions to take into account the
      headgroup-counterion specificity and address ion-specific effects on the cmc and
      aggregation number. We assume that the charged headgroup and the counterion at
      the Stern layer form solvent-shared ion pair with different degrees of cosphere
      overlap. The thickness of the Stern layer is estimated from molecular structures
      of hydrated surfactant heads and hydrated counterions, and from the knowledge of
      the qualitative strength of headgroup-counterion interaction in line with
      Collins' concept of matching water affinities. Our proposed thermodynamic model
      properly predicts the cmc of both anionic and cationic surfactants of various
      counterions, and the effect of different inorganic salts on micellization of
      ionic surfactants.

PMID- 20809603
TI  - Alkoxy tail length dependence of gelation ability and supramolecular chirality of
      sugar-appended organogelators.
AB  - A series of sugar-appended organogelators, 4-(4'-alkoxyphenyl)phenyl-beta-O-D
      glucoside (GBCn, where n = 1-12 denotes the number of carbon atom in the tail),
      are synthesized to elucidate the effect of terminal chain length on their
      gelation and chiral expression abilities in gels. In the mixture of H(2)O/dioxane
      (60/40 v/v), GBCn undergoes a phasic evolution of precipitation-solution-gel
      precipitation-gel as its tail length increases from n = 1, 2, 3-6, and 7-10 to 11
      12, respectively. Helical ribbons are observed in gels, but platelet-like
      structures are the dominant morphologies in the systems that precipitation
      happens. Combinatory analyses of microscopic, spectroscopic, and diffraction
      results reveal that the self-assembly into interdigitated bilayer structures of
      GBCn is driven by hydrogen bondings of sugar heads, pi-pi interactions of
      biphenyl rods, and hydrophobic interactions of alkoxy tails. The helical
      morphology formation is caused by the significant steric repulsion between chiral
      moieties on the condition of the disordering or the size of alkoxy chains
      reaching the threshold of helical twisting and bending.

PMID- 20809604
TI  - Experimental and numerical investigation of the equilibrium geometry of liquid
      lenses.
AB  - The equilibrium configuration of a nonwetted three fluid system takes the form of
      a floating liquid lens, where the lens resides between an upper and lower phase.
      The axisymmetric profiles of the three interfaces can be computed by solving the
      nonlinear Young-Laplace differential equation for each interface with coupled
      boundary conditions at the contact line. Here we describe a numerical method
      applicable to sessile or pendant lenses and provide a free, downloadable
      Mathematica Player file which uses a graphical interface for analyzing and
      plotting lens profiles. The results of the calculations were compared to optical
      photographs of various liquid lens systems which were analyzed using basic ray
      tracing and Moire imaging. The lens profile calculator, together with a
      measurement of the lens radius for a known volume, provides a simple and
      convenient method of determining the spreading coefficient (S) of a liquid lens
      system if all other fluid parameters are known. If surfactants are present, the
      subphase surface tension must also be self-consistently determined. A procedure
      is described for extracting characteristic features in the optical images to
      uniquely determine both parameters. The method gave good agreement with
      literature values for pure fluids such as alkanes on water and also for systems
      with a surfactant (hexadecane/DTAB), which show a transition from partial wetting
      to the pseudopartial wetting regime. Our technique is the analog of axisymmetric
      drop shape analysis, applied to a three fluid system.

PMID- 20809605
TI  - In-gel technology for PCR genotyping and pathogen detection.
AB  - This work describes the use of polyacrylamide gel and PCR reagents
      photopolymerized in a mold to create an array of semisolid posts that serve as
      reaction vessels for parallel PCR amplification of an externally added template.
      DNA amplification occurred in a cylindrical, self-standing 9 * 9 array of gel
      posts each less than 1 MUL in volume. Photopolymerization of the gel with an
      intercalating dye added prior to polymerization permitted acquisition of real
      time PCR data and melting curve analysis data without the need for any type of
      post-PCR staining procedures. PCR was equally efficient and reproducible when
      template DNA was polymerized within the gel or when exogenous template was added
      atop precast gel posts. PCR amplification occurred with template from purified
      DNA or from raw urine of patients with BK viruria. Multiple primer sets can be
      utilized per gel post array with no detectable cross contamination. As few as 34
      BK virus templates were consistently detected by PCR in an individual gel post.
      Amplification of HPA1 and FGFR2 genes in human genomic DNA (gDNA) required as
      little as 2-5 ng of gDNA template/gel post. The device prototype includes a
      Peltier element for PCR thermal cycling and a CCD camera to capture fluorescence
      for product detection. Our technology is amenable to integration in point of care
      microdevices.

PMID- 20809606
TI  - High-resolution electrospray ionization mass spectrometry analysis of water
      soluble organic aerosols collected with a particle into liquid sampler.
AB  - This work demonstrates the utility of a particle-into-liquid sampler (PILS), a
      technique traditionally used for identification of inorganic ions present in
      ambient or laboratory aerosols, for the analysis of water-soluble organic aerosol
      (OA) using high-resolution electrospray ionization mass spectrometry (HR-ESI-MS).
      Secondary organic aerosol (SOA) was produced from 0.5 ppm mixing ratios of
      limonene and ozone in a 5 m(3) Teflon chamber. SOA was collected simultaneously
      using a traditional filter sampler and a PILS. The filter samples were later
      extracted with either water or acetonitrile, while the aqueous PILS samples were
      analyzed directly. In terms of peak abundances, types of detectable compounds,
      average O/C ratios, and organic mass to organic carbon ratios, the resulting high
      resolution mass spectra were essentially identical for the PILS and filter based
      samples. SOA compounds extracted from both filter/acetonitrile extraction and
      PILS/water extraction accounted for >95% of the total ion current in the ESI mass
      spectra. This similarity was attributed to high solubility of limonene SOA in
      water. In contrast, significant differences in detected ions and peak abundances
      were observed for pine needle biomass burning organic aerosol (BBOA) collected
      with PILS and filter sampling. The water-soluble fraction of BBOA is considerably
      smaller than for SOA, and a number of unique peaks were detectable only by the
      filter/acetonitrile method. The combination of PILS collection with HR-ESI-MS
      analysis offers a new approach for molecular analysis of the water-soluble
      organic fraction in biogenic SOA, aged photochemical smog, and BBOA.

PMID- 20809607
TI  - Growth of multiple metal/semiconductor nanoheterostructures through point and
      line contact reactions.
AB  - Forming functional circuit components in future nanotechnology requires
      systematic studies of solid-state chemical reactions in the nanoscale. Here, we
      report efficient and unique methods, point and line contact reactions on Si
      nanowires, fabricating high quality and quantity of multiple nanoheterostructures
      of NiSi/Si and investigation of NiSi formation in nanoscale. By using the point
      contact reaction between several Ni nanodots and a Si nanowire carried out in
      situ in an ultrahigh vacuum transmission electron microscopy, multiple sections
      of single-crystal NiSi and Si with very sharp interfaces were produced in a Si
      nanowire. Owing to the supply limited point contact reaction, we propose that the
      nucleation and growth of the sugar cane-type NiSi grains start at the middle of
      the point contacts between two Ni nanodots and a Si nanowire. The reaction
      happens by the dissolution of Ni into the Si nanowire at the point contacts and
      by interstitial diffusion of Ni atoms within a Si nanowire. The growth of NiSi
      stops as the amount of Ni in the Ni nanodots is consumed. Additionally, without
      lithography, utilizing the line contact reaction between PS nanosphere-mediated
      Ni nanopatterns and a nanowire of Si, we have fabricated periodic multi
      NiSi/Si/NiSi heterostructure nanonowires that may enhance the development of
      circuit elements in nanoscale electronic devices. Unlike the point contact
      reaction, silicide growth starts at the contact area in the line contact
      reaction; the different silicide formation modes resulting from point and line
      contact reactions are compared and analyzed. A mechanism on the basis of flux
      divergence is proposed for controlling the growth of the nano
      multiheterostructures.

PMID- 20809608
TI  - Para-derivatized pybox ligands as sensitizers in highly luminescent Ln(III)
      complexes.
AB  - New complexes of pyridine-bis(oxazoline) derivatized with -H, -OMe, and -Br at
      the para position of the pyridine ring with Eu(III) and Tb(III) have been
      isolated. These are highly luminescent in the solid state, regardless of the
      ligand-to-metal ratio. Several of the metal complexes were isolated and
      characterized by single crystal X-ray diffraction, showing the rich diversity of
      structures that can be obtained with this family of ligands.
      [Eu(PyboxOMe)(3)](NO(3))(3).3CH(2)Cl(2), 1, crystallizes in the monoclinic space
      group P2(1)/n and has the cell parameters a = 14.3699(10) A, b = 13.4059(9) A, c
      = 25.8766(18) A, beta = 95.367(1) degrees , and V = 4963.1(6) A(3). The
      isostructural [Tb(PyboxOMe)(3)](NO(3))(3).3CH(2)Cl(2), 2, crystallizes with the
      parameters a = 14.4845(16) A, b = 13.2998(15) A, c = 25.890(3) A, beta =
      94.918(2) degrees , and V = 4969.1(10) A(3). 3, a 1:1 complex with the formula
      [Eu(PyboxBr)(NO(3))(3)(H(2)O)], crystallizes in the monoclinic P2(1)/c space
      group with a = 11.649(2) A, b = 8.3914(17) A, c = 20.320(4) A, beta = 100.25(3)
      degrees , and V = 1954.5(7) A(3). 4, a product of the reaction of PyboxBr with
      Tb(NO(3))(3), is [Tb(PyboxBr)(2)(eta(2)-NO(3))(eta(1)
      NO(3)](2)[Tb(NO(3))(5)].5H(2)O. It crystallizes in the monoclinic space group
      P2(1) with a = 15.612(3) A, b = 14.330(3) A, c = 16.271(3) A, beta = 92.58(3)
      degrees , and V = 3636.5(13) A(3). [Tb(Pybox)(3)](CF(3)SO(3))(3).3CH(2)CN, 5,
      crystallizes in the triclinic space group P1 with a = 12.3478(2) A, b =
      15.0017(2) A, c = 16.1476(4) A, alpha = 100.252(1) degrees , beta = 100.943(1)
      degrees , gamma = 113.049(1) degrees , and V = 2594.80(8) A(3). Finally, compound
      6, [Tb(Pybox)(2)(NO(3))(H(2)O)](NO(3))(2).CH(3)OH, crystallizes in the triclinic
      P1 space group with a = 9.7791(2) A, b = 10.1722(2) A, c = 15.3368(3) A, alpha =
      83.753(1) degrees , beta = 78.307(1) degrees , gamma = 85.630(1) degrees , and V
      = 1482.33(5) A(3). In solution, the existence of 3:1, 2:1, and 1:1 species can be
      observed through absorption and luminescence speciation measurements as well as
      NMR spectroscopy. The stability constants in acetonitrile, as an average obtained
      from absorption and emission titrations, are log beta(11) = 5.4, log beta(12) =
      8.8, and log beta(13) = 12.8 with Eu(III) and log beta(11) = 4.5, log beta(12) =
      8.4, and log beta(13) = 11.7 for the Tb(III) species with PyboxOMe. Pybox
      displayed stability constants log beta(11) = 3.6, log beta(12) = 9.1, and log
      beta(13) = 12.0 with Eu(III) and log beta(11) = 3.7, log beta(12) = 9.3, and log
      beta(13) = 12.2 for the Tb(III) species. Finally, PyboxBr yielded log beta(11) =
      7.1, log beta(12) = 12.2, and log beta(13) = 15.5 for the Eu(III) species and log
      beta(11) = 6.2, log beta(12) = 11.0, and log beta(13) = 15.4 with Tb(III).
      Photophysical characterization was performed in all cases on solutions with 3:1
      ligand-to-metal ion stoichiometry and allowed determination of quantum yields and
      lifetimes of emission for PyboxOMe of 23.5 +/- 1.6% and 1.54 +/- 0.04 ms for
      Eu(III) and 21.4 +/- 3.6% and 1.88 +/- 0.04 ms for Tb(III). For Pybox these
      values were 25.6 +/- 1.1% and 1.49 +/- 0.04 ms for Eu(III) and 23.2 +/- 2.1% and
      0.44 +/- 0.01 ms for Tb(III) and for PyboxBr they were 35.8 +/- 1.6% and 1.46 +/-
      0.03 ms for Eu(III) and 23.3 +/- 1.3% and a double lifetime of 0.79 +/- 0.05/0.07
      +/- 0.01 ms for Tb(III). A linear relationship between the triplet level energies
      and the Hammett sigma constants was found. Lifetime measurements in methanol as
      well as the NMR data in both methanol and acetonitrile indicate that all
      complexes are stable in the 3:1 stoichiometry in solution and that there is no
      solvent coordination to the metal ion.

PMID- 20809609
TI  - Phase transfer catalysts drive diverse organic solvent solubility of single
      walled carbon nanotubes helically wrapped by ionic, semiconducting polymers.
AB  - Use of phase transfer catalysts such as 18-crown-6 enables ionic, linear
      conjugated poly[2,6-{1,5-bis(3
      propoxysulfonicacidsodiumsalt)}naphthylene]ethynylene (PNES) to efficiently
      disperse single-walled carbon nanotubes (SWNTs) in multiple organic solvents
      under standard ultrasonication methods. Steady-state electronic absorption
      spectroscopy, atomic force microscopy (AFM), and transmission electron microscopy
      (TEM) reveal that these SWNT suspensions are composed almost exclusively of
      individualized tubes. High-resolution TEM and AFM data show that the interaction
      of PNES with SWNTs in both protic and aprotic organic solvents provides a self
      assembled superstructure in which a PNES monolayer helically wraps the nanotube
      surface with periodic and constant morphology (observed helical pitch length = 10
      +/- 2 nm); time-dependent examination of these suspensions indicates that these
      structures persist in solution over periods that span at least several months.
      Pump-probe transient absorption spectroscopy reveals that the excited state
      lifetimes and exciton binding energies of these well-defined nanotube
      semiconducting polymer hybrid structures remain unchanged relative to analogous
      benchmark data acquired previously for standard sodium dodecylsulfate (SDS)-SWNT
      suspensions, regardless of solvent. These results demonstrate that the use of
      phase transfer catalysts with ionic semiconducting polymers that helically wrap
      SWNTs provide well-defined structures that solubulize SWNTs in a wide range of
      organic solvents while preserving critical nanotube semiconducting and conducting
      properties.

PMID- 20809610
TI  - Photophysical properties and electropolymerization of gold complexes of 3,3''
      diethynyl-2,2':5',2''-terthiophene.
AB  - The preparation and crystal structures of 3,3''-diethynyl-2,2':5',2''
      terthiophene (A(2)T(3)) and three Au(I) complexes containing this ligand are
      reported. One of the complexes, Au(2)(dppm)(A(2)T(3)), has a short Au-Au distance
      (3.1969 A) because of an aurophilic interaction. UV/vis absorption and emission
      spectra of the complexes and ligand at 298 and 85 K and photoinduced electron
      transfer to methyl viologen are reported. A(2)T(3) and two of the complexes may
      be electropolymerized, and the resulting gold-containing films were characterized
      by X-ray photoelectron spectroscopy (XPS) and cyclic voltammetry.

PMID- 20809611
TI  - Wide InP nanowires with wurtzite/zincblende superlattice segments are type-II
      whereas narrower nanowires become type-I: an atomistic pseudopotential
      calculation.
AB  - Nanowire-superlattices with different structural phases along the nanowire
      direction, such as wurtzite (WZ) and zincblende (ZB) forms of the same compound,
      often exhibit a "type II" band-alignment with electrons on ZB and holes on WZ.
      This is a material property of most of III-V semiconductors. We show via InP
      nanowires that as the nanowire diameter decreases, quantum-confinement alters
      this basic material property, placing both electrons and holes on the same (ZB)
      phase. This structural design causes a dramatic increase in absorption strength
      and reduced radiative lifetime.

PMID- 20809612
TI  - Biotransformation of cycloastragenol by Cunninghamella blakesleeana NRRL 1369
      resulting in a novel framework.
AB  - The microbial transformation of cycloastragenol by the fungus Cunninghamella
      blakesleeana NRRL 1369 was investigated. Unlike the original compound, the
      metabolite was found to possess an interesting triterpenic skeleton derived via
      an exceptional transformation involving ring cleavage and methyl group migration.
      The structure of the new metabolite was elucidated by 1-D ((1)H, (13)C) and 2-D
      NMR (COSY, HMBC, HMQC, NOESY) techniques and MS analyses.

PMID- 20809613
TI  - Acetoacetanilides as masked isocyanates: facile and efficient synthesis of
      unsymmetrically substituted ureas.
AB  - A general and practical method for the preparation of unsymmetrically substituted
      ureas has been developed. By the reactions of acetoacetanilides with various
      amines including primary/secondary amines, a series of substituted aryl ureas
      were achieved in high yields. Acetoacetanilide substrates can be considered as
      masked reagents that liberate reactive isocyanates in situ.

PMID- 20809614
TI  - Palladium-catalyzed direct arylation of free NH2-substituted thiophene
      derivatives.
AB  - The palladium-catalyzed direct 2- or 5-arylation of some free NH(2)-substituted
      thiophene derivatives was found to proceed in high yields using a variety of aryl
      bromides. In the course of these reactions, no coupling of the aryl bromide with
      the thiophene NH(2) substituent was detected. The presence of an ester
      substituent on C2 of thiophene was found to be useful to block this highly
      reactive carbon.

PMID- 20809615
TI  - Global mortality attributable to aircraft cruise emissions.
AB  - Aircraft emissions impact human health though degradation of air quality. The
      majority of previous analyses of air quality impacts from aviation have
      considered only landing and takeoff emissions. We show that aircraft cruise
      emissions impact human health over a hemispheric scale and provide the first
      estimate of premature mortalities attributable to aircraft emissions globally. We
      estimate ~8000 premature mortalities per year are attributable to aircraft cruise
      emissions. This represents ~80% of the total impact of aviation (where the total
      includes the effects of landing and takeoff emissions), and ~1% of air quality
      related premature mortalities from all sources. However, we note that the impact
      of landing and takeoff emissions is likely to be under-resolved. Secondary
      H(2)SO(4)-HNO(3)-NH(3) aerosols are found to dominate mortality impacts. Due to
      the altitude and region of the atmosphere at which aircraft emissions are
      deposited, the extent of transboundary air pollution is particularly strong. For
      example, we describe how strong zonal westerly winds aloft, the mean meridional
      circulation around 30-60 degrees N, interaction of aircraft-attributable aerosol
      precursors with background ammonia, and high population densities in combination
      give rise to an estimated ~3500 premature mortalities per year in China and India
      combined, despite their relatively small current share of aircraft emissions.
      Subsidence of aviation-attributable aerosol and aerosol precursors occurs
      predominantly around the dry subtropical ridge, which results in reduced wet
      removal of aviation-attributable aerosol. It is also found that aircraft NO(x)
      emissions serve to increase oxidation of nonaviation SO(2), thereby further
      increasing the air quality impacts of aviation. We recommend that cruise
      emissions be explicitly considered in the development of policies, technologies
      and operational procedures designed to mitigate the air quality impacts of air
      transportation.

PMID- 20809616
TI  - Tracking antibiotic resistance genes in the South Platte River basin using
      molecular signatures of urban, agricultural, and pristine sources.
AB  - A novel approach utilizing antibiotic-resistance-gene (ARG) molecular signatures
      was applied to track the sources of ARGs at sites along the Cache la Poudre
      (Poudre) and South Platte Rivers in Colorado. Two lines of evidence were
      employed: (1) detection frequencies of 2 sulfonamide and 11 tetracycline ARGs and
      (2) tet(W) phylotype and phylogenetic analysis. A GIS database indicating the
      locations of wastewater treatment plants (WWTPs) and animal feeding operations
      (AFOs) in the watershed was also constructed to assess congruence of the
      surrounding landscape with the putative sources identified by ARG molecular
      signatures. Discriminant analysis was performed on detection frequencies of
      tetARG groups that were previously identified to be associated with either WWTPs
      or AFOs. All but one (South Platte River-3, just downstream from the confluence
      with the Poudre River) of the eight sites were classified as primarily WWTP
      influenced based on discriminant analysis of ARG detection frequencies. tet(W)
      phylotype analysis also aligned South Platte River-3 with putative AFO sources,
      while phylogenetic analysis indicated that it was not significantly different
      from the AFOs or WWTPs investigated. South Platte River-3 is situated in an
      intense agricultural area, but the upstream portion of the South Platte River
      receives substantial loading from metropolitan Denver. By contrast, tet(W)
      phylotype and phylogenetics of site Poudre River-4, located 4 km downstream of a
      WWTP, was also characterized and found to be significantly different from the AFO
      lagoons (p < 0.05), as expected. In general, a good correspondence was found
      between classification of the impacted river sites and the surrounding landscape.
      While the overall approach could be extended to other watersheds, the general
      findings indicate that transport of ARGs from specific sources is likely the
      dominant mechanism for ARG proliferation in this riverine environment relative to
      selection of ARGs among native bacteria by antibiotics and other pollutants.

PMID- 20809617
TI  - Nutrient and oxygen concentrations within the sediments of an Alaskan beach
      polluted with the Exxon Valdez oil spill.
AB  - Measurements of the background concentrations of nutrients, dissolved oxygen
      (DO), and salinity were obtained from a beach that has oil from the Exxon Valdez
      oil spill in 1989. Two transects were set across the beach, one passed through an
      oil patch while the other transect was clean. Three pits were dug in each
      transect, and they ranged in depth from 0.9 to 1.5 m. The DO was around 1.0 mg L(
      1) at oiled pits and larger than 5 mg L(-1) at clean pits. The average nutrient
      concentrations in the beach were 0.39 mg-N L(-1) and 0.020 mg-P L(-1). Both
      concentrations are lower than optimal values for oil biodegradation (2 to 10 mg-N
      L(-1) and 0.40 to 2.0 mg-P L(-1)), which suggests that they are both limiting
      factors for biodegradation. The lowest nitrate and DO values were found in the
      oiled pits, leading to the conclusion that microbial oil consumption was probably
      occurring under anoxic conditions and was associated to denitrification. We
      present evidence that the oxygen level may be a major factor limiting oil
      biodegradation in the beaches.

PMID- 20809618
TI  - Probing the acid-base equilibrium in acid-benzimidazole complexes by 1H NMR
      spectra and density functional theory calculations.
AB  - The acid-base equilibrium in acid (phenylphosphonic acid, methylsulfonic acid,
      phosphoric acid, hydrochloric acid, acetic acid, and sulfuric acid)-benzimidazole
      (BIm) complexes was studied by (1)H NMR spectra, FTIR spectra, and density
      functional theory (DFT) calculations. The DFT optimized structures of the acid
      BIm complexes, the vibrational frequencies of the acidic protons, and potential
      profiles were applied to study the equilibrium between the acids and BIm. In gas
      phase, it was shown that the strong sulfuric acid could completely protonate BIm
      and the other acids could only incompletely protonate BIm. When the polarizable
      continuum model of DMSO was applied, it was shown that all the acids could
      completely protonate BIm, except the weak acetic acid and phenylphosphonic acid.
      Furthermore, the potential profile for the PPoA-BIm shows double-well structure
      facilitating the free movement of the acidic proton between PPoA and BIm. If an
      explicit solvent molecule of DMSO was included into an acid-BIm complex,
      significant changes in equilibrium between acid and BIm are observed. The
      potential profiles for the MSA-BIm and HCl-BIm show very flat bottom wells,
      facilitating the free movement of proton between the acid and BIm. These
      calculations were consistent with the (1)H NMR chemical shifts of the immobile
      protons of the benzimidazole ring in DMSO-d(6) and the FTIR spectra of the acid
      BIm complexes.

PMID- 20809619
TI  - Time-dependent atomistic view on the electronic relaxation in light-harvesting
      system II.
AB  - Aiming at a better understanding of the molecular details in light absorption
      during photosynthesis, spatial and temporal correlation functions as well as
      spectral densities have been determined. At the focus of the present study are
      the light-harvesting II complexes of the purple bacterium Rhodospirillum
      molischianum. The calculations are based on a time-dependent combination of
      molecular dynamics simulations and quantum chemistry methods. Using a 12 ps long
      trajectory, different quantum chemical methods have been compared to each other.
      Furthermore, several approaches to determine the couplings between the individual
      chromophores have been tested. Correlations between energy gap fluctuations of
      different individual pigments are analyzed but found to be negligible. From the
      energy gap fluctuations, spectral densities are extracted which serve as input
      for calculations of optical properties and exciton dynamics. To this end, the
      spectral densities are tested by determining the linear absorption of the
      complete two-ring system. One important difference from earlier studies is given
      by the severely extended length of the trajectory along which the quantum
      chemical calculations have been performed. Due to this extension, more accurate
      and reliable data have been obtained in the low frequency regime which is
      important in the dynamics of electronic relaxation.

PMID- 20809620
TI  - Asymmetric total synthesis of vindorosine, vindoline, and key vinblastine
      analogues.
AB  - Concise asymmetric total syntheses of vindoline (1) and vindorosine (2) are
      detailed based on a unique intramolecular [4 + 2]/[3 + 2] cycloaddition cascade
      of 1,3,4-oxadiazoles inspired by the natural product structures. A chiral
      substituent on the tether linking the dienophile and oxadiazole was used to
      control the facial selectivity of the initiating Diels-Alder reaction and set the
      absolute stereochemistry of the remaining six stereocenters in the cascade
      cycloadduct. This key reaction introduced three rings and four C-C bonds central
      to the pentacyclic ring system setting all six stereocenters and introducing
      essentially all the functionality found in the natural products in a single step.
      Implementation of the approach for the synthesis of 1 and 2 required the
      development of a ring expansion reaction to provide a 6-membered ring suitably
      functionalized for introduction of the Delta(6,7)-double bond found in the core
      structure of the natural products. Two unique approaches were developed that
      defined our use of a protected hydroxymethyl group as the substituent that
      controls the stereochemical course of the cycloaddition cascade. In the course of
      these studies, several analogues of vindoline were prepared containing deep
      seated structural changes presently accessible only by total synthesis. These
      analogues, bearing key modifications at C6-C8, were incorporated into vinblastine
      analogues and used to probe the unusual importance (100-fold) and define the
      potential role of the vinblastine Delta(6,7)-double bond.

PMID- 20809621
TI  - Profiling of phenols in human fecal water after raspberry supplementation.
AB  - The phenolic compositions of fecal water samples from ten free-living human
      subjects without marked dietary restrictions were monitored before and after
      intake of raspberry puree (200 g/day, 4 days) using gas chromatography-mass
      spectrometry. No single phenolic component was increased in all subjects after
      intake, but a majority of subjects had significant elevations in phenylacetic
      acid (7/10), 4-hydroxyphenylacetic acid (6/10), 3-hydroxyphenylacetic acid
      (5/10), 3-phenylpropionic acid and 3-(4-hydroxyphenyl)propionic acid. The levels
      of 3,4-dihydroxbenzoic acid were elevated in 8/10 subjects, significantly for 6
      subjects (p < 0.05), and not significantly reduced in the other 2 subjects. In
      addition, unlike most other fecal metabolites, the increase was always >2-fold.
      This metabolite may be representative of the increased colonic dose of cyanidin
      anthocyanins. The colonic microbiota varied greatly between individuals, and
      supplementation with raspberries did not produce any statistically significant
      alterations in the profile of colonic bacteria, nor was a common pattern revealed
      to account for the interindividual variations observed in the fecal water
      phenolic profiles.

PMID- 20809622
TI  - Enzymatic method to measure beta-1,3-beta-1,6-glucan content in extracts and
      formulated products (GEM assay).
AB  - An enzymatic method to measure beta-glucan content (GEM assay) is applicable in a
      variety of matrices. The method is composed of swelling the sample with KOH and
      initial digestion with a lyticase, which is followed by treatment with a mixture
      of exo-1,3-beta-d-glucanase and beta-glucosidase that converts the beta-glucan to
      glucose. The glucose generated by the enzymatic hydrolysis is measured by another
      enzymatic method. The method is shown to be accurate and precise. The method is
      selective and applicable to both highly branched and unbranched beta-1,3-glucans.

PMID- 20809623
TI  - Rhodium-catalyzed asymmetric arylation of N-tosyl ketimines.
AB  - A rhodium-catalyzed addition of sodium tetraarylborates to N-tosyl ketimines is
      described. Highly efficient asymmetric catalysis has been achieved by employing a
      chiral diene ligand, constructing chiral amine derivatives possessing alpha
      tetrasubstituted carbon stereocenters with high enantioselectivity.

PMID- 20809624
TI  - Utilizing protein-lean coproducts from corn containing recombinant pharmaceutical
      proteins for ethanol production.
AB  - Protein-lean fractions of corn (maize) containing recombinant (r) pharmaceutical
      proteins were evaluated as a potential feedstock to produce fuel ethanol. The
      levels of residual r-proteins in the coproduct, distillers dry grains with
      solubles (DDGS), were determined. Transgenic corn lines containing recombinant
      green fluorescence protein (r-GFP) and a recombinant subunit vaccine of
      Escherichia coli enterotoxin (r-LTB), primarily expressed in endosperm, and
      another two corn lines containing recombinant human collagen (r-CIalpha1) and r
      GFP, primarily expressed in germ, were used as model systems. The kernels were
      either ground and used for fermentation or dry fractionated to recover germ-rich
      fractions prior to grinding for fermentation. The finished beers of whole ground
      kernels and r-protein-spent endosperm solids contained 127-139 and 138-155 g/L
      ethanol concentrations, respectively. The ethanol levels did not differ among
      transgenic and normal corn feedstocks, indicating the residual r-proteins did not
      negatively affect ethanol production. r-Protein extraction and germ removal also
      did not negatively affect fermentation of the remaining mass. Most r-proteins
      were inactivated during the mashing process used to prepare corn for
      fermentation. No functionally active r-GFP or r-LTB proteins were found after
      fermentation of the r-protein-spent solids; however, a small quantity of residual
      r-CIalpha1 was detected in DDGS, indicating that the safety of DDGS produced from
      transgenic grain for r-protein production needs to be evaluated for each event.
      Protease treatment during fermentation completely hydrolyzed the residual r
      CIalpha1, and no residual r-proteins were detectable in DDGS.

PMID- 20809625
TI  - Potentiometric online detection of aromatic hydrocarbons in aqueous phase using
      carbon nanotube-based sensors.
AB  - Surfaces made of entangled networks of single-walled carbon nanotubes (SWCNTs)
      display a strong adsorption affinity for aromatic hydrocarbons. Adsorption of
      these compounds onto the walls of SWCNTs changes the electrical characteristics
      of the SWCNT-solution interface. Using these features, we have developed a
      potentiometric sensor to detect neutral aromatic species. Specifically, we can
      detect online aromatic hydrocarbons in industrial coolant water. Our
      chromatographic results confirm the adsorption of toluene onto the walls of
      carbon nanotubes, and our impedance spectroscopy data show the change in the
      double layer capacitance of the carbon nanotube-solution interface upon addition
      of toluene, thus confirming the proposed sensing mechanism. The sensor showed a
      toluene concentration dependent EMF response that follows the shape of an
      adsorption isotherm and displayed an immediate response to the presence of
      toluene with a detection limit of 2.1 ppm. The sensor does not respond to other
      nonaromatic hydrocarbons that may coexist with aromatic hydrocarbons in water. It
      shows a qualitative sensitivity and selectivity of 100% and 83%, respectively,
      which confirms its ability to detect aromatic hydrocarbons in aqueous solutions.
      The sensor showed an excellent ability to immediately detect the presence of
      toluene in actual coolant water. Its operational characteristics, including its
      fast response, low cost, portability, and easy use in online industrial
      applications, improve those of current chromatographic or spectroscopic
      techniques.

PMID- 20809626
TI  - Group 6 carbon monoxide-releasing metal complexes with biologically-compatible
      leaving groups.
AB  - A series of carbon monoxide-releasing molecules (CO-RMs) based on the M(CO)(5)
      framework (M = Cr, Mo, W) is reported. The metal carbonyl anions [MCl(CO)(5)](-)
      are shown to be highly versatile precursors to Group 6 pentacarbonyl complexes
      containing amino-ester groups, namely, [M(CO)(5)(NH(2)CH{R}CO(2)R')]. The
      structures of five of the complexes, including an enantiomeric pair based on (R)
      and (S)-alanine, were determined by single crystal X-ray diffraction. These
      species exhibit rapid CO-release, as shown by a myoglobin-based assay. The rate
      of release is affected by the nature of both the metal and the amino-ester
      employed. A mechanistic study shows that a common intermediate is formed
      corresponding to loss of the amino-ester from the metal. In addition, a further
      series of potential CO-RMs have been prepared based on Fischer-type carbenes
      complexes, which contain either amino esters or amino acids. The amino esters and
      amino acids are introduced into the coordination sphere of the metal by a
      nucleophilic substitution reaction at the carbene carbon atom. The Michael
      addition of NH(2)CH(2)CO(2)Et across the triple bond in [Cr(CO)(5)(?C{OMe}
      C=CPh)] affords crystallographically characterized [Cr(CO)(5)(?C{OMe}-(Z)
      CH?C{Ph}NHCH(2)CO(2)Et)]. The rate of CO-release from the carbene complexes
      depends primarily on the specific heteroatom connected to the carbene center.
      Rapid CO-release is observed in the case of sulfur- and methoxy-stabilized
      carbenes whereas in the case of amino-substituted carbenes, release is far more
      sluggish. This may be correlated with the electrophilic character at the carbene
      carbon atom.

PMID- 20809627
TI  - Torque-induced slip of the rotary motor F1-ATPase.
AB  - F(1)-ATPase plays an essential role in cellular metabolism by linking rotational
      motion to ATP hydrolysis/synthesis. We measure the torque profile of F(1) in both
      ATP hydrolysis and synthesis directions using a novel magnetic nanorod assay.
      F(1) is found to decouple ATP synthesis from rotary motion at a surprisingly low
      torque. This low-torque slip mechanism protects the enzyme from excessive load
      and may play a broader biological role by reducing the production of reactive
      oxygen species.

PMID- 20809628
TI  - Tracing origins of complex pharmaceutical preparations using surface desorption
      atmospheric pressure chemical ionization mass spectrometry.
AB  - A novel strategy to trace the origins of commercial pharmaceutical products has
      been developed based on the direct chemical profiling of the pharmaceutical
      products by surface desorption atmospheric pressure chemical ionization mass
      spectrometry (DAPCI-MS). Besides the unambiguous identification of active drug
      components, various compounds present in the matrixes are simultaneously detected
      without sample pretreatment, providing valuable information for drug quality
      control and origin differentiation. Four sources of commercial amoxicillin
      products made by different manufacturers have been successfully differentiated.
      This strategy has been extended to secerning six sources of Liuwei Dihuang
      Teapills, which are herbal medicine preparations with extremely complex matrixes.
      The photolysis status of chemical drug products and the inferior natural herd
      medicine products prepared with different processes (e.g., extra heating) were
      also screened using the method reported here. The limit of detection achieved in
      the MS/MS experiments was estimated to be 1 ng/g for amoxicillin inside the
      capsule product. Our experimental data demonstrate that DAPCI-MS is a useful tool
      for rapid pharmaceutical analysis, showing promising perspectives for tracking
      the entire pharmaceutical supply chain to prevent counterfeit intrusions.

PMID- 20809629
TI  - A scanning frequency mode for ion cyclotron mobility spectrometry.
AB  - A new operational mode for an ion cyclotron mobility spectrometry instrument is
      explored as a possible means of performing high-resolution separations. The
      approach is based on oscillating fields that are applied to segmented regions of
      a circular drift tube. Ions with mobilities that are resonant with the frequency
      of field application are transmitted while nonresonant species are eliminated. An
      ion mobility spectrum is obtained by scanning the drift field application
      frequency. The approach is demonstrated by examining mixtures of ions produced by
      electrospraying the substance P peptide, as well as a mixture of tryptic peptides
      obtained by enzymatic digestion of cytochrome c. Drift field application
      frequency scans of substance P peptide ions show that it is possible to separate
      [M+2H](2+) ions, and compact and elongated forms of [M+3H](3+) ions. The
      resolution of different ions is related to the number of cycles for the analysis.
      At high cycle numbers (>50 3/4 or a drift length of 9242.03 cm) values of the
      resolving power can exceed 300 with a maximum resolving power of ~400. The
      ability to tune the resolving power of a mobility-based separation by varying the
      ion cycle number has substantial analytical utility.

PMID- 20809630
TI  - Isolation and identification of radical scavenging and tyrosinase inhibition of
      polyphenols from Tibouchina semidecandra L.
AB  - Phytochemical and bioactivity studies of the leaves and stem barks of Tibouchina
      semidecandra L. have been carried out. The ethyl acetate extract of the leaves
      yielded four flavonoid compounds, identified as quercetin, quercetin 3-O-alpha-l
      (2''-O-acetyl) arabinofuranoside, avicularin, and quercitrin, while the stem
      barks gave one ellagitannin, identified as 3,3'-O-dimethyl ellagic acid 4-O-alpha
      l-rhamnopyranoside. Evaluation of the antioxidative activity on the crude
      extracts and pure compounds by electron spin resonance (ESR) and ultraviolet
      visible (UV-vis) spectrophotometric assays showed that the pure isolated
      polyphenols and the EtOAc extract possessed strong antioxidative capabilities.
      Quercetin was found to be the most active radical scavenger in DPPH-UV and ESR
      methods with SC(50) values of 0.7 MUM +/- 1.4 and 0.7 MUM +/- 0.6 MUM,
      respectively, in the antioxidant assay. A combination of quercetin and quercitrin
      was tested for synergistic antioxidative capacity;, however, there was no
      significant improvement observed. Quercetin also exhibited strong antityrosinase
      activity with a percent inhibition of 95.0% equivalent to the positive control,
      kojic acid, in the tyrosinase inhibition assay.

PMID- 20809631
TI  - A strategy for the synthesis of well-defined iron catalysts and application to
      regioselective diene hydrosilylation.
AB  - We report the development of a well-defined Fe catalyst and its application to
      the regio- and stereoselective 1,4-hydrosilylation of 1,3-dienes. To the best of
      our knowledge, this is the first example of accessing a characterized low-valent
      Fe catalyst by controlled reductive elimination from a readily accessible Fe
      precatalyst.

PMID- 20809632
TI  - Rigid analogues of the alpha2-adrenergic blocker atipamezole: small changes, big
      consequences.
AB  - We report the discovery of a new family of alpha(2) adrenergic receptor
      antagonists derived from atipamezole. Affinities of the compounds at human
      alpha(2) and alpha(1b) receptors as well as their functional activities at
      halpha(2A) receptors were determined in competition binding and G-protein
      activation assays, respectively. Central alpha(2) antagonist activities were
      confirmed in mice after oral administration. Further studies on a selected
      example: (+)-4-(1a,6-dihydro-1H-cyclopropa[a]inden-6a-yl)-1H-imidazole, (+)-1 (F
      14805), were undertaken to probe the potential of the series. On the one hand,
      (+)-1 increased the release of noradrenaline in mouse frontal cortex following
      acute systemic administration, the magnitude of this effect being much larger
      than that obtained with reference agents. On the other, (+)-1 produced minimal
      cardiovascular effects in intact, anesthetized rat, a surprising outcome that
      might be explained by its differential action at peripheral and central alpha(2)
      receptors. A strategy for improving the therapeutic window of alpha(2)
      antagonists is put forward.

PMID- 20809633
TI  - Design, synthesis, and structure-activity relationships of novel bicyclic azole
      amines as negative allosteric modulators of metabotropic glutamate receptor 5.
AB  - A novel series of diaryl bicyclic azole-amines that are potent selective negative
      modulators of metabotropic glutamate receptor 5 (mGluR5) were identified through
      rational design. An initial hit compound 5a of modest potency (IC(50) = 1.2 MUM)
      was synthesized. Evaluation of structure-activity relationships (SAR) on the left
      hand side of the molecule revealed a preference for a 2-substituted pyridine
      group linked directly to the central heterocycle. Variation of the central azolo
      amine portion of the molecule revealed a preference for the [4,5-c]
      oxazoloazepine scaffold, while right-hand side variants showed a preference for
      ortho- and meta-substituted benzene rings linked directly to the tertiary amine
      of the saturated heterocycle. These iterations led to the synthesis of 29b, a
      potent (IC(50) = 16 nM) and selective negative modulator that showed good brain
      penetrance, high receptor occupancy, and a duration of action greater than 1 h in
      rat when administered intraperitoneally. Formal PK studies in rat and Rhesus
      monkey revealed a short half-life that was attributable to high first-pass
      clearance.

PMID- 20809634
TI  - Amino derivatives of indole as potent inhibitors of isoprenylcysteine carboxyl
      methyltransferase.
AB  - The enzyme isoprenylcysteine carboxyl methyltransferase (Icmt) plays an important
      role in the post-translational modification of proteins that are involved in the
      regulation of cell growth. The indole acetamide cysmethynil is by far the most
      potent and widely investigated Icmt inhibitor, but it has modest
      antiproliferative activity and may have pharmacokinetic limitations due to its
      lipophilic character. We report here that cysmethynil can be structurally
      modified to give analogues that are as potent in inhibiting Icmt but with
      significantly greater antiproliferative activity. Key modifications were the
      replacement of the acetamide side chain by tertiary amino groups, the n-octyl
      side chain by isoprenyl and the 5-m-tolyl ring by fluorine. Moreover, these
      analogues have lower lipophilicities that could lead to improved pharmacokinetic
      profiles.

PMID- 20809635
TI  - Peptide-binding sites as revealed by the crystal structures of the human Hsp40
      Hdj1 C-terminal domain in complex with the octapeptide from human Hsp70.
AB  - Heat shock protein (Hsp) 40s play essential roles in cellular processes by
      cooperating with Hsp70 proteins. Hsp40 proteins recognize non-native
      polypeptides, deliver these peptides to Hsp70 proteins, and stimulate the ATPase
      activity of Hsp70 proteins to facilitate the correct folding of the polypeptides.
      We have determined the crystal structures of the C-terminal peptide-binding
      domain of human Hsp40 Hdj1 (CTD) and of its complex with the C-terminal
      octapeptide of human Hsp70, (634')GPTIEEVD(641'). CTD exists as a twisted,
      horseshoe-shaped homodimer. The protomer consists of two domains, I and II, with
      similar topologies. The octapeptides are located in two sites, 1 and 2, of domain
      I. In site 1, the octapeptide forms an antiparallel beta-sheet with CTD. The
      negatively charged residues of the EEVD motif in the octapeptide form
      electrostatic interactions with the positively charged Lys residues of CTD. The
      Ile side chain of the octapeptide fits into the narrow concave formed by the
      hydrophobic residues of CTD. In site 2, the octapeptide also forms an
      antiparallel beta-sheet with CTD, and the EEVD motif forms electrostatic
      interactions. The side chains of Pro and Ile of the octapeptide interact with the
      hydrophobic surface region of CTD site 2, which is broader and shallower than the
      concave binding region of site 1. This region seems to be capable of binding
      hydrophobic side chains that are bulkier than the Ile side chain. The roles of
      these two peptide-binding sites of Hdj1 are discussed.

PMID- 20809636
TI  - Organellar protein complexes of Caco-2 human cells analyzed by two-dimensional
      blue native/SDS-PAGE and mass spectrometry.
AB  - The complexome is essential for a better understanding of protein functions. In
      order to study protein complexes, an approach allowing the extraction and the
      analysis in native conditions is needed. Two-dimensional blue native/SDS-PAGE (2D
      BN/SDS-PAGE) technology is thus an interesting and powerful approach for this
      purpose. This report deals with the analysis and the identification of the
      organellar protein complexes of Caco-2 human cells using 2D BN/SDS-PAGE and HPLC
      chip-MS. We identified 58 protein complexes (26 heteromultimeric and 32
      homomultimeric complexes) and 4 monomeric proteins. Among them, 32 protein
      complexes were pointed out, providing insights into the function of previously
      uncharacterized human proteins.

PMID- 20809637
TI  - Free energy landscapes of iduronic acid and related monosaccharides.
AB  - The pyranose ring of L-iduronic acid (IdoA), a major constituent of the
      anticoagulant heparin, is an equilibrium of multiple ring puckers that have
      evaded quantification by experiment or computation. In order to resolve this
      enigma, we have calculated the free energy landscape of IdoA and two related
      monosaccharides from extensive microsecond simulations. After establishing that
      the simulated puckers had reached equilibrium, hypotheses were confirmed that (a)
      IdoA (1)C(4)- and (4)C(1)-chair conformations exchange on the microsecond time
      scale, (b) C5 epimerization leads to a (4)C(1)-chair, and (c) IdoA 2-O-sulfation
      (IdoA2S) stabilizes the (1)C(4) conformer. The IdoA and IdoA2S (1)C(4) conformers
      were isoenergetic and computed to be 0.9 and 2.6 kcal mol(-1) lower in free
      energy than their respective (4)C(1)-chair conformations. The simulations also
      predicted that the IdoA (2)S(O)-skew-boat was less populated than previously
      thought. Novel chemical synthesis and ultra-high-field NMR supported these
      observations, but slight discrepancies in observed and predicted NMR vicinal
      couplings implied that the simulation overestimated the population of the IdoA
      (4)C(1)-chair with respect to (1)C(4)-chair due to small force field inaccuracies
      that only manifest in long simulations. These free-energy calculations drive
      improvements in computational methods and provide a novel route to carbohydrate
      mimetic biomaterials and pharmaceuticals.

PMID- 20809639
TI  - Development of a new s-tetrazine-based copolymer for efficient solar cells.
AB  - A new s-tetrazine-based low-bandgap semiconducting polymer, PCPDTTTz, was
      designed and synthesized. This is the first solution-processable conjugated
      polymer with tetrazine in the main chain. This polymer shows good thermal
      stability and broad absorption covering 450-700 nm. The HOMO and LUMO energy
      levels were estimated to be -5.34 and -3.48 eV, with an electrochemical bandgap
      of 1.86 eV. Simple polymer solar cells based on PCPDTTTz and PC(71)BM exhibit a
      calibrated power conversion efficiency of 5.4%.

PMID- 20809638
TI  - Selective complexation of K+ and Na+ in simple polarizable ion-ligating systems.
AB  - An influx of experimental and theoretical studies of ion transport protein
      structure has inspired efforts to understand underlying determinants of ionic
      selectivity. Design principles for selective ion binding can be effectively
      isolated and interrogated using simplified models composed of a single ion
      surrounded by a set of ion-ligating molecular species. While quantum mechanical
      treatments of such systems naturally incorporate electronic degrees of freedom,
      their computational overhead typically prohibits thorough dynamic sampling of
      configurational space and, thus, requires approximations when determining ion
      selective free energy. As an alternative, we employ dynamical simulations with a
      polarizable force field to probe the structure and K(+)/Na(+) selectivity in
      simple models composed of one central K(+)/Na(+) ion surrounded by 0-8 identical
      model compounds: N-methylacetamide, formamide, or water. In the absence of
      external restraints, these models represent gas-phase clusters displaying relaxed
      coordination structures with low coordination number. Such systems display Na(+)
      selectivity when composed of more than ~3 organic carbonyl-containing compounds
      and always display K(+) selectivity when composed of water molecules. Upon
      imposing restraints that solely enforce specific coordination numbers, we find
      all models are K(+)-selective when ~7-8-fold ion coordination is achieved.
      However, when models composed of the organic compounds provide ~4-6-fold
      coordination, they retain their Na(+) selectivity. From these trends, design
      principles emerge that are of basic importance in the behavior of K(+) channel
      selectivity filters and suggest a basis not only for K(+) selectivity but also
      for modulation of block and closure by smaller ions.

PMID- 20809640
TI  - Fluorescence quenching by photoinduced electron transfer in the Zn2+ sensor
      zinpyr-1: a computational investigation.
AB  - We report a detailed study of luminescence switching in the fluorescent zinc
      sensor Zinpyr-1 by density functional methods. A two-pronged approach employing
      both time-dependent density functional theory (TDDFT) and constrained density
      functional theory (CDFT) is used to characterize low-lying electronically excited
      states of the sensor. The calculations indicate that fluorescence activation in
      the sensor is governed by a photoinduced electron transfer mechanism in which the
      energy level ordering of the excited states is altered by binding Zn(2+). While
      the sensor is capable of binding two Zn(2+) cations, a single Zn(2+) ion appears
      to be sufficient to activate moderate fluorescence in aqueous solution at
      physiological pH. We show that it is reasonable to consider the tertiary amine as
      the effective electron donor in this system, although the pyridyl nitrogens each
      contribute some density to the xanthone ring. The calculations illustrate an
      important design principle: because protonation equilibria at receptor sites can
      play a determining role in the sensor's fluorescence response, receptor sites
      with a pK(a) near the pH of the sample are to be disfavored if a sensor governed
      by a simple PET fluorescence quenching model is desired.

PMID- 20809641
TI  - Synthesis of ester prodrugs of 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-2,6
      diaminopurine (HPMPDAP) as anti-poxvirus agents.
AB  - 9-(S)-[3-Hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine (HPMPDAP) and its
      cyclic form were selected for further evaluation as potential drug candidates
      against poxvirus infections. To increase bioavailability of these compounds,
      synthesis of their structurally diverse ester prodrugs was carried out:
      alkoxyalkyl (hexadecyloxypropyl, octadecyloxyethyl, hexadecyloxyethyl),
      pivaloyloxymethyl (POM), 2,2,2-trifluoroethyl, butylsalicylyl, and prodrugs based
      on peptidomimetics. Most HPMPDAP prodrugs were synthesized in the form of
      monoesters as well as the corresponding cyclic phosphonate esters. The activity
      was evaluated not only against vaccinia virus but also against different herpes
      viruses. The most potent and active prodrugs against vaccinia virus were the
      alkoxyalkyl ester derivatives of HPMPDAP, with 50% effective concentrations 400
      600-fold lower than those of the parent compound. Prodrugs based on
      peptidomimetics, the 2,2,2-trifluoroethyl, the POM, and the butylsalicylyl
      derivatives, were able to inhibit vaccinia virus replication at 50% effective
      concentrations that were equivalent or ~10-fold lower than those observed for the
      parent compounds.

PMID- 20809642
TI  - Click-chemistry-derived triazole ligands of arginine-glycine-aspartate (RGD)
      integrins with a broad capacity to inhibit adhesion of melanoma cells and both in
      vitro and in vivo angiogenesis.
AB  - A click chemistry approach was applied for the discovery of triazole-based
      arginine-glycine-aspartate (RGD) mimetics by Cu(I)-catalyzed 1,3-dipolar alkyne
      azide coupling reaction, which showed binding affinity properties toward
      alpha(v)beta(3)/alpha(v)beta(5) integrins. Biological assays showed compound 18
      capable of binding alpha(v)beta(3) integrin with nanomolar affinity according to
      a two-sites model, and molecular modeling studies revealed a peculiar pi-stacking
      interaction between the triazole ring and Tyr178 side chain. Accordingly,
      compound 18 inhibited the adhesion of integrin-expressing human melanoma cells to
      RGD-containing proteins of the extracellular matrix, such as vitronectin,
      fibronectin, and osteopontin, and also angiogenesis in in vitro and in vivo
      experimental models. The relevant biological effects exerted by compound 18
      suggest its potential application as an antiangiogenic agent in the diagnosis and
      therapy of tumors where alpha(v)beta(3) integrin expression is up-regulated.

PMID- 20809643
TI  - Dynamics of the excited states of [Ir(ppy)2bpy]+ with triple phosphorescence.
AB  - We investigated the relaxation dynamics of bis(2-phenylpyridinato-)(2,2'
      bipyridine)iridium(III), [Ir(ppy)(2)bpy](+) using the technique of time-resolved
      spectroscopy. In the visible emission spectra this molecule exhibits triple
      phosphorescence: displaying blue, green, and orange bands. From the dependence of
      spectral shifts with polarity of solvent, decay lifetimes, and the results of
      calculations using time-dependent density functional theory, we assigned these
      three emitting states to be triplet interligand charge-transfer ((3)LLCT), metal
      to-ligand ppy charge transfer ((3)MLCT(ppy)), and metal-to-ligand bpy charge
      transfer ((3)MLCT(bpy)) states. The blue states were formed promptly after
      excitation at wavelength 355 nm; the one lying at higher energy decaying with a
      time coefficient 0.79-2.56 ns is assigned to be a triplet MLCT, and the other at
      lower energy decaying in 1.5-2.8 MUs is assigned to (3)LLCT(A), A symmetry. This
      decay time coefficient of (3)LLCT(A) decreases with increasing dielectric
      constant of the solvent indicating this state mixing of some MLCT character. The
      green state (3)MLCT(ppy) decays in 0.13-4.8 ns to a nearby intermediate state
      either (3)MLCT(ppy) or (3)MLCT(bpy). The orange state (3)MLCT(bpy) is coupled to
      the intermediate state to have a rise time about 0.36-0.84 ns and decays in 425
      617 ns. Although many triplet states exist in a small energy range, they couple
      weakly to display triple emission. All (3)LLCT and (3)MCLT states are coupled to
      the singlet (1)LLCT manifold directly and/or indirectly and contribute to the
      emission in the visible range.

PMID- 20809644
TI  - Isomerization of neopentyl chloride and neopentyl bromide by a 1,2-interchange of
      a halogen atom and a methyl group.
AB  - The recombination of chloromethyl and t-butyl radicals at room temperature was
      used to generate neopentyl chloride molecules with 89 kcal mol(-1) of internal
      energy. The observed unimolecular reactions, which give 2-methyl-2-butene and 2
      methyl-1-butene plus HCl, as products, are explained by a mechanism that involves
      the interchange of a methyl group and the chlorine atom to yield 2-chloro-2
      methylbutane, which subsequently eliminates hydrogen chloride by the usual four
      centered mechanism to give the observed products. The interchange isomerization
      process is the rate-limiting step. Similar experiments were done with CD(2)Cl and
      C(CH(3))(3) radicals to measure the kinetic-isotope effect to help corroborate
      the proposed mechanism. Density functional theory was employed at the B3PW91/6
      31G(d',p') level to verify the Cl/CH(3) interchange mechanism and to characterize
      the interchange transition state. These calculations, which provide vibrational
      frequencies and moments of inertia of the molecule and transition state, were
      used to evaluate the statistical unimolecular rate constants. Matching the
      calculated and experimental rate constants, gave 62 +/- 2 kcal mol(-1) as the
      threshold energy for interchange of the Cl atom and a methyl group. The
      calculated models also were used to reinterpret the thermal unimolecular
      reactions of neopentyl chloride and neopentyl bromide. The previously assumed
      Wagner-Meerwein rearrangement mechanism for these reactions can be replaced by a
      mechanism that involves the interchange of the halogen atom and a methyl group
      followed by HCl or HBr elimination from 2-chloro-2-methylbutane and 2-bromo-2
      methylbutane. Electronic structure calculations also were done to find threshold
      energies for several related molecules, including 2-chloro-3,3-dimethylbutane, 1
      chloro-2-methyl-2-phenylpropane, and 1-chloro-2-methyl-2-vinylpropane, to
      demonstrate the generality of the interchange reaction involving a methyl, or
      other hydrocarbon groups, and a chlorine atom. The interchange of a halogen atom
      and a methyl group located on adjacent carbon atoms can be viewed as an extension
      of the halogen atom interchange mechanisms that is common in 1,2-dihaloalkanes.

PMID- 20809645
TI  - Aptamer-functionalized in situ injectable hydrogel for controlled protein
      release.
AB  - Various in situ injectable hydrogels have been developed for protein delivery in
      treating human diseases. However, most hydrogels are highly permeable, which can
      lead to the rapid release of loaded proteins. The purpose of this study is to
      apply nucleic acid aptamers to functionalize an in situ injectable hydrogel model
      to control the release of proteins. The aptamers were studied using secondary
      structural predictions and binding analyses. The results showed that the
      structural predictions were different from the experimental measurements in
      numerous cases. The affinity of the aptamer was significantly affected by the
      mutations of the essential nucleotides, whereas it was not significantly affected
      by the variations of the nonessential nucleotides. The mutated aptamers were then
      used to functionalize the injectable hydrogel model. The results showed that the
      aptamer-functionalized hydrogel could prolong protein release. Moreover, the
      release rates could be controlled by adjusting the affinity of the aptamer.

PMID- 20809646
TI  - Dietary intake of aluminum in a Spanish population (Canary Islands).
AB  - The aim of this study was to analyze the aluminum content in foods and beverages
      most commonly consumed by the Canary Island population to determine the dietary
      intake of this metal throughout the Canary Islands as a whole and in each of the
      seven islands (Gran Canaria, Lanzarote, Fuerteventura, Tenerife, La Palma, La
      Gomera, and El Hierro). Four hundred and forty samples were analyzed by ICP-OES.
      Estimated total intake of aluminum for the Canary population was 10.171 mg/day,
      slightly higher than the provisional tolerable weekly intake (PTWI; 10 mg/day for
      a person weighing 70 kg). Aluminum intake by age and sex of the Canary Island
      population was also determined and compared values from other populations, both
      national and international.

PMID- 20809647
TI  - Essential oils, phenolics, and antioxidant activities of different parts of cumin
      (Cuminum cyminum L.).
AB  - Cuminum cyminum L. roots, stems and leaves, and flowers were investigated for
      their essential oils, total phenolics, flavonoids, and tannins contents,
      individual phenolic compounds, and antioxidant activities. The essential oil was
      investigated by gas chromatography (GC) and gas chromatography-mass spectrometry
      (GC-MS), whereas identification and quantification of individual target
      polyphenolic compounds was performed by reversed-phase high-performance liquid
      chromatography (RP-HPLC). Essential oil yields were 0.03% in roots, 0.1% in stem
      and leaves, and 1.7% in flowers. Major components of the oils were bornyl acetate
      (23%), alpha-terpinene (34%), and gamma-terpinene (51%) in roots, stems and
      leaves, and flowers, respectively. In all C. cyminum organs, total phenolics
      content ranged from 11.8 to 19.2 mg of gallic acid equivalents per gram of dry
      weight (mg of GAE/g of DW). Among the polyphenols studied, 13 were identified in
      roots, 17 in stem and leaves, and 15 in flowers. The major phenolic compound in
      the roots was quercetin (26%), whereas in the stems and leaves, p-coumaric,
      rosmarinic, trans-2-dihydrocinnamic acids and resorcinol were predominant. In the
      flowers, vanillic acid was the main compound (51%). The antioxidant activities of
      C. cyminum essential oils and acetone extracts obtained from the three organs
      were assessed using four tests [1,1-diphenyl-2-picrylhydrazyl (DPPH), beta
      carotene/linoleic acid, reducing power, and chelating power assays]. The acetone
      extract of flowers was strongly effective as a DPPH radical scavenger, lipid
      peroxidation inhibitor, and reducing agent, with IC(50) values of 4, 32, and 8
      MUg/mL, respectively. Moreover, the acetone extract of stems and leaves showed
      the highest chelating power. However, the essential oils exhibited moderate
      activities in the different tests.

PMID- 20809648
TI  - Pericyclic reaction of a zwitterionic salt of an enedione-diazoester. A novel
      strategy for the synthesis of highly functionalized resorcinols.
AB  - Enedione-diazoesters formed from 3-TBSO-2-diazo-3-butenoates undergo base
      catalyzed pericyclization that with dinitrogen extrusion and methyl migration
      provide a novel and efficient route to 2-carboalkoxyresorcinols. Intercepting the
      intermediate enolate anion with methyl vinyl ketone leads to the corresponding 4
      substituted 2-carboalkoxyresorcinol and suggests generalization of this
      methodology.

PMID- 20809649
TI  - Dinaphthoporphycenes.
AB  - Naphthobipyrrole is a potentially useful building block for porphyrin and
      porphyrin analogue synthesis. Reported here is a simple, generalizable synthetic
      route to alpha-formylated, beta-substituted naphthobipyrroles and their use in
      the preparation of binaphthoporphycenes. The resulting binaphthoporphycenes
      possess a planar geometry as determined via a single-crystal X-ray diffraction
      analysis; they also display absorption maxima that are bathochromically shifted
      compared to simple porphycenes.

PMID- 20809650
TI  - Conformational changes and substrate recognition in Pseudomonas aeruginosa D
      arginine dehydrogenase.
AB  - DADH catalyzes the flavin-dependent oxidative deamination of d-amino acids to the
      corresponding alpha-keto acids and ammonia. Here we report the first X-ray
      crystal structures of DADH at 1.06 A resolution and its complexes with
      iminoarginine (DADH(red)/iminoarginine) and iminohistidine
      (DADH(red)/iminohistidine) at 1.30 A resolution. The DADH crystal structure
      comprises an unliganded conformation and a product-bound conformation, which is
      almost identical to the DADH(red)/iminoarginine crystal structure. The active
      site of DADH was partially occupied with iminoarginine product (30% occupancy)
      that interacts with Tyr53 in the minor conformation of a surface loop. This
      flexible loop forms an "active site lid", similar to those seen in other enzymes,
      and may play an essential role in substrate recognition. The guanidinium side
      chain of iminoarginine forms a hydrogen bond interaction with the hydroxyl of
      Thr50 and an ionic interaction with Glu87. In the structure of DADH in complex
      with iminohistidine, two alternate conformations were observed for iminohistidine
      where the imidazole groups formed hydrogen bond interactions with the side chains
      of His48 and Thr50 and either Glu87 or Gln336. The different interactions and
      very distinct binding modes observed for iminoarginine and iminohistidine are
      consistent with the 1000-fold difference in k(cat)/K(m) values for d-arginine and
      d-histidine. Comparison of the kinetic data for the activity of DADH on different
      d-amino acids and the crystal structures in complex with iminoarginine and
      iminohistidine establishes that this enzyme is characterized by relatively broad
      substrate specificity, being able to oxidize positively charged and large
      hydrophobic d-amino acids bound within a flask-like cavity.

PMID- 20809651
TI  - Catalytic asymmetric synthesis of quaternary alpha-hydroxy trifluoromethyl
      phosphonate via chiral aluminum(III) catalyzed hydrophosphonylation of
      trifluoromethyl ketones.
AB  - The chiral hydrogenated tridentate Schiff base-aluminum(III) complex has been
      first applied in the catalytic enantioselective hydrophosphonylation of
      trifluoromethyl ketones. The side reactions related to phospha-Brook
      rearrangement were completely avoided, and the corresponding quaternary alpha
      hydroxy trifluoromethyl phosphonates have been first synthesized in good yields
      with high enantioselectivities (up to 90% ee).

PMID- 20809652
TI  - Construction of hexagonal prisms of variable size via coordination-driven
      multicomponent self-assembly.
AB  - The coordination-driven self-assembly of supramolecular hexagonal prisms has been
      achieved upon mixing a hexakis[4-(4-pyridyl)phenyl]benzene donor ligand and
      carboxylate donor ligands such as sodium terephthalate, sodium (1,1'-biphenyl)
      4,4'-dicarboxylate, sodium 4,4'-(diazene-1,2-diyl)dibenzoate, and 4,4'-dipyridyl
      with cis-Pt(PEt(3))(2)(OTf)(2) in a 1:3:6 ratio. Four assembled hexagonal prisms
      have been characterized by (31)P and (1)H NMR multinuclear spectroscopy as well
      as electrospray ionization mass spectrometry. Molecular force-field simulations
      provide the possible conformation and size of each structure.

PMID- 20809654
TI  - Nature of sodium atoms/(Na(+), e(-)) contact pairs in liquid tetrahydrofuran.
AB  - With no internal vibrational or rotational degrees of freedom, atomic solutes
      serve as the simplest possible probe of a condensed-phase environment's influence
      on solute electronic structure. Of the various atomic species that can be formed
      in solution, the quasi-one-electron alkali atoms in ether solvents have been the
      most widely studied experimentally, primarily due to the convenient location of
      their absorption spectra at visible wavelengths. The nature of solvated alkali
      atoms, however, remains controversial: the consensus view is that solvated alkali
      atoms exist as (Na(+), e(-)) tight-contact pairs (TCPs), species in which the
      alkali valence electron is significantly displaced from the alkali nucleus and
      confined primarily by the first solvent shell. Thus, to shed light on the nature
      of alkali atoms in solution and to further our understanding of condensed-phase
      effects on solutes' electronic structure, we have performed mixed
      quantum/classical molecular dynamics simulations of sodium atoms in liquid
      tetrahydrofuran (Na(0)/THF). Our interest in this particular system stems from
      recent pump-probe experiments in our group, which found that the rate at which
      this species is solvated depends on how it was created ( Science 2008 , 321 ,
      1817 ); in other words, the solvation dynamics of this system do not obey linear
      response. Our simulations reproduce the experimental spectroscopy of this system
      and clearly indicate that neutral Na atoms exist as (Na(+), e(-)) TCPs in
      solution. We find that the driving force for the displacement of sodium's valence
      electron is the formation of a tight solvation shell around the partially exposed
      Na(+). On average, four THF oxygens coordinate the cation end of the TCP;
      however, we also observe fluctuations to other solvent coordination numbers.
      Furthermore, we find that species with different solvent coordination numbers
      have unique absorption spectra and that interconversion between species with
      different solvent coordination numbers requires surmounting a free energy barrier
      of several k(B)T. Taken together, our results suggest that the Na(0)/THF species
      with different solvent coordination numbers may be viewed as chemically distinct.
      Thus, we can explain the kinetics of Na TCP formation as being dictated by
      changes in the Na(+) solvent coordination number, and we can understand the
      dependence on initial conditions seen in the solvation dynamics of this system as
      resulting from the fact that the important solvent coordinate involves the motion
      of only a few molecules in the first solvation shell.

PMID- 20809656
TI  - Synthesis of the sponge-derived plakortone series of bioactive compounds.
AB  - The Caribbean sponges of the genus Plakortis, P. halichondrioides, and P. simplex
      have provided a series of biologically active furanolactones-the plakortones A-D
      (1-4) from the former sponge and B-F (2-6) from the latter. The defining motif of
      the plakortones is a sterically congested 2,6-dioxabicyclo[3.3.0]octan-3-one
      moiety, the emblematic furanolactone core. This core is efficiently accessed by a
      palladium(II) mediated hydroxycyclization-carbonylation-lactonization cascade
      with an appropriate ene-1,3-diol. Total syntheses of plakortones C (3) and F (6)
      are now described which settle constitutional and stereochemical features in this
      group of secondary metabolites. Acquisition of plakortone D (4), the most
      effective activator of SR-Ca(2+)-pumping ATPase, utilized stereodefined lactone
      cores that resulted from asymmetric dihydroxylation of protected homoallylic
      alcohol 29. A derived lactone aldehyde was then coupled with an independently
      generated, sulfone-activated side chain unit, 57. The 11,12-E-double bond,
      carried through the sequence as a protected, stereodefined diol, was released
      therefrom by stereospecific syn-elimination via an orthoester derivative. In this
      way, plakortone D (4) was demonstrated to possess the (3S,4S,6S,10R,11E)
      configuration. Racemic plakortone E (5) was also acquired by using the Pd(II)
      induced sequence, but in this case, the required, complete acyclic system 52 was
      assembled first. Plakortone C (3) resulted from a sequence commencing with (R)
      (+)-3-hydroxy-2-methylpropionate, with a derived iodide 76 alkylating the enolate
      of the butyramide 77 generated from (1S,2S)-(+)-pseudoephedrine. The liberated
      primary alcohol 79 was converted by standard procedures to key enediol 89 which,
      with the Pd(II) protocol, afforded the major separable plakortones 90 and 91,
      with the former being identical with natural plakortone C (3). Very mild
      hydrogenation of 90 afforded a saturated plakortone, identical with natural
      plakortone F (6), thus establishing its structure and absolute stereochemistry.
      Available information on the stereoselective routes to plakortones E (5) and B
      (2) are also outlined, so that the constitution and absolute stereochemistry of
      plakortones B-F are now established.

PMID- 20809657
TI  - Stereocontrolled photodimerization with congested 1,8-bis(4'-anilino)naphthalene
      templates.
AB  - Suzuki cross-coupling of a 1,8-dihalonaphthalene with 4-methoxy-3
      methylphenylboronic acid or 4-acetamidophenylboronic acid and subsequent
      functional group transformation gave 1,8-bis(3'-methyl-4'-anilino)naphthalene,
      16, and 1,8-bis(4'-anilino)naphthalene, 21, in 65% and 90% overall yield,
      respectively. These congested compounds exhibit two cofacial aniline rings that
      favor a proximate, parallel arrangement of covalently attached cinnamoyl units
      suitable for stereoselective photodimerization. The [2 + 2]cycloaddition was
      found to proceed with high yield and exclusive formation of cis,trans,cis
      cyclobutane-1,2-dicarboxylic acids. Amide formation with cinnamoyl chloride and
      template 21 followed by photochemical dimerization and acidic hydrolysis gave
      beta-truxinic acid, 10, in 69% overall yield. Coupling of 21 and (E)-3-(3,4
      dimethylphenyl)acrylic acid in the presence of EDC, UV irradiation, and cleavage
      gave cis,trans,cis-3,4-bis(3,4-dimethylphenyl)cyclobutane-1,2-dicarboxylic acid,
      26, in 60% yield. In both cases, the template was quantitatively recovered.

PMID- 20809655
TI  - Evidence of the E*-E equilibrium from rapid kinetics of Na+ binding to activated
      protein C and factor Xa.
AB  - Na(+) binding to thrombin enhances the procoagulant and prothrombotic functions
      of the enzyme and obeys a mechanism that produces two kinetic phases: one fast
      (in the microsecond time scale) due to Na(+) binding to the low activity form E
      to produce the high activity form E:Na(+) and another considerably slower (in the
      millisecond time scale) that reflects a pre-equilibrium between E and the
      inactive form E*. In this study, we demonstrate that this mechanism also exists
      in other Na(+)-activated clotting proteases like factor Xa and activated protein
      C. These findings, along with recent structural data, suggest that the E*-E
      equilibrium is a general feature of the trypsin fold.

PMID- 20809658
TI  - Changes of the molecular structure in polyelectrolyte multilayers under stress.
AB  - Polyelectrolyte multilayers (PEMs) produced by layer-by-layer (LbL) self-assembly
      find different applications. Often the PEMs are exposed to mechanical stress
      which they have to sustain. A correlation of the mechanical properties of PEM on
      macroscopic level with the ordering of polyelectrolyte molecules on molecular
      level is of interest. Our study is focused on the changes of orientation of the
      polyelectrolyte molecules when the PEM is under lateral mechanical stress. The
      PEM was prepared from pyrene (PY) labeled polystyrene sulfonate (PSS-PY) and
      poly(diallyldimethylammonium) chloride (PDDA) on sheets of polydimethylsiloxane
      (PDMS) rubber used as substrates. The LbL dipping technique was used for the
      formation of PEMs. A special stretching device was constructed which allows the
      fluorescence of the films under stress to be observed. The change in the
      fluorescence spectra which can be attributed to a PY ordering change from the PEM
      under stress of up to 10% was monitored. We observed that PEMs undergo a plastic
      deformation under external mechanical stretching. We conclude that under
      mechanical stress the polyelectrolyte molecules organized in polyelectrolyte
      multilayers experience an irreversible transition from the coiled to decoiled
      state.

PMID- 20809659
TI  - An approach to lauroxanes by iterative use of Co(2)(CO)(6)-acetylenic complexes.
      a formal synthesis of (+)-laurencin.
AB  - A new approach to lauroxanes by a powerful and highly convergent methodology
      based on iterative use of Co(2)(CO)(6)-acetylenic complexes is described. The
      strategy employs an intermolecular Nicholas reaction to form unsaturated branched
      linear ethers, a ring closing metathesis to obtain the cobalt complex cyclic
      ethers, and an isomerization promoted by montmorillonite K-10. A short synthesis
      of cyclic ethers of seven-, eight-, and nine-membered rings is described.
      Additionally, the methodology is exemplified by the formal synthesis of (+)
      laurencin, a red algae metabolite.

PMID- 20809660
TI  - Metronomic chemotherapy for metastatic prostate cancer: a 'young' concept for old
      patients?
AB  - Prostate cancer is a common disease in the elderly, and the number of older
      prostate cancer patients will probably increase with both the aging of the
      population and the increased rate of screening. In elderly patients with several
      co-morbidities, cancer management can be complex, and the risk of administering
      toxic therapy in this setting should be carefully evaluated. Metronomic
      chemotherapy, i.e. low-dose, long-term, frequently administered chemotherapy, has
      been shown to have a significant stabilizing effect on cancer and a positive
      impact on the quality of life of patients, including those with prostate cancer.
      Given the low toxicity profile of metronomic chemotherapy, elderly patients or
      patients with co-morbidities may be candidates for a first-line or second-line
      oral metronomic approach when standard chemotherapies are contraindicated or not
      acceptable to the patient. Moreover, the possibility of patients being able to
      spend more time at home is an important component of a palliative treatment such
      as metronomic chemotherapy. Unfortunately, and despite these considerations, very
      few data are available on the activity and safety of metronomic chemotherapy in
      elderly patients. However, retrospective analyses conducted in a small cohort of
      patients have been published and, notwithstanding their limitations, indicate
      that novel metronomic schedules are well tolerated, safe and show potentially
      interesting activity in elderly, 'unfit' (poor performance status) patients with
      metastatic prostate cancer. Therefore, evaluation of metronomic chemotherapy
      strategies in prospective, randomized, phase II/III clinical studies of elderly
      patients with metastatic prostate cancer appears to be warranted.

PMID- 20809661
TI  - Vulnerable elderly patients and overactive bladder syndrome.
AB  - Overactive bladder (OAB) prevalence increases with age, and the elderly
      population is rapidly increasing worldwide, particularly those aged >or=75 years.
      OAB symptoms may be associated with co-morbid conditions, particularly bowel
      symptoms and falls related to nighttime lavatory trips, as well as with higher
      rates of mortality in elderly persons. Physical changes associated with age that
      result in altered bladder function and altered drug solubility, metabolism and
      clearance, as well as increased polypharmacy, may impact disease management in
      elderly patients. Clinical trial data indicate that current treatments for OAB
      are generally effective and well tolerated in elderly patients. However, clinical
      trial participants have generally been relatively healthy persons aged >or=65
      years, which may not reflect the true elderly population. Limited data exist that
      are specific to the vulnerable elderly, who have been defined as patients aged
      >or=65 years who are at increased risk of functional decline or death over a 2
      year period. Identification and treatment of vulnerable elderly patients with OAB
      is important, because intervention may limit functional deterioration.
      Antimuscarinics are associated with improvement in OAB symptoms and health
      related quality of life in older patients, although adverse effects such as
      constipation may be of particular concern in vulnerable elderly patients.
      Additional research is needed on the potential impact of antimuscarinics on
      cognition in vulnerable elderly persons. Behavioural interventions, including
      biofeedback, prompted voiding and pelvic floor muscle exercises, may be effective
      in some elderly patients without risk of adverse events, and they may enhance the
      efficacy of antimuscarinic treatment. The International Consultation on
      Incontinence has recommended behavioural interventions with the cautious addition
      and trial of antimuscarinic drugs for the treatment of urinary incontinence in
      frail elderly individuals or those already in a state of decline; these
      recommendations may also be useful for vulnerable individuals. Greater
      representation of vulnerable elderly individuals in clinical trials, the
      development and inclusion of outcomes relevant to this population, and the
      creation and testing of validated, evidence-based models to guide treatment
      decisions in vulnerable elderly individuals are needed.

PMID- 20809662
TI  - Management of mixed dementia.
AB  - Alzheimer's disease (AD) and vascular dementia (VaD) are the most common causes
      of dementia in the elderly. Although AD can be diagnosed with a considerable
      degree of accuracy, the distinction between isolated AD, VaD and mixed dementia
      (MD) [when both pathologies coexist in the same patient] remains a controversial
      issue and one of the most difficult diagnostic challenges. MD represents a very
      common pathology, especially in the elderly, as reported in neuropathological
      studies. Accurate diagnosis of MD is of crucial significance for epidemiological
      purposes and for preventive and therapeutic strategies. Until recently,
      pharmacological studies have generally focused on pure disease, either AD or VaD,
      and have provided few data on the best therapeutic approach to MD. There is only
      one original randomized clinical trial on (acetyl)cholinesterase inhibitor
      therapy (GAL-INT-6, galantamine) for MD; the other studies are post hoc analyses
      of AD trial subgroups (AD2000, donepezil) or of VaD trial subgroups (VantagE,
      rivastigmine). Cholinesterase inhibitors have reproducible beneficial effects on
      cognitive and functional outcomes in patients with MD. These benefits are of a
      similar magnitude to those previously reported for the treatment of AD. It is
      likely that the beneficial effects of memantine (an NMDA receptor antagonist) in
      AD may also apply to MD, but randomized controlled trials are still lacking.
      Treatment of cardiovascular risk factors, especially hypertension, may protect
      brain function and should be included in prevention strategies for MD.

PMID- 20809663
TI  - Pharmacological therapies for osteoarthritis of the hand: a review of the
      evidence.
AB  - Osteoarthritis (OA) of the hand is highly prevalent in US senior citizens,
      developing in >50% of individuals aged >60 years. Hormonal, genetic and
      inflammatory mechanisms are known to increase the risk of hand OA and influence
      the course of the disease. However, the underlying processes in the development
      of hand OA are not well understood, and there is no known disease-modifying drug.
      Likewise, surgical interventions for affected hand joints have not proven as
      successful as joint replacement for the knee or hip. Current treatment of hand OA
      focuses on reducing pain and improving patient function to improve quality of
      life. Pharmacological approaches have included several oral therapies, such as
      paracetamol (acetaminophen), oral nonsteroidal anti-inflammatory drugs (NSAIDs)
      and opioids, all of which carry a risk of adverse events that typically increases
      with age. Topical NSAIDs, recently approved in the US, appear to provide efficacy
      similar to that of oral NSAIDs for hand OA, with less systemic NSAID exposure.
      Intra-articular corticosteroids and hyaluronic acid have also shown modest
      symptomatic efficacy with generally good tolerability. Two proposed disease
      modifying therapies, chondroitin sulfate and hydroxychloroquine, have had unclear
      effects on disease modification in clinical trials. This review of
      pharmacotherapies for the treatment of hand OA focuses on their efficacy and
      safety in elderly patients. Articles cited herein were identified via a search of
      PubMed from January 2005 to November 2009. The bibliographies of articles
      identified through this search were searched manually for additional references
      of interest.

PMID- 20809664
TI  - Potentially inappropriate drug prescriptions and risk of hospitalization among
      older, Italian, nursing home residents: the ULISSE project.
AB  - BACKGROUND: Potentially inappropriate medications in older patients increase the
      risk of adverse drug events, which are an important cause of hospital admission
      and death among hospitalized patients. Little information is available about the
      prevalence of potentially inappropriate drug prescriptions (PIDPs) and the
      related health adverse outcomes among nursing home (NH) residents. OBJECTIVE: To
      estimate the prevalence of PIDPs and the association with adverse outcomes in NH
      residents. METHODS: A total of 1716 long-term residents aged >or=65 years
      participating in the ULISSE (Un Link Informatico sui Servizi Sanitari Esistenti
      per l'anziano [A Computerized Network on Health Care Services for Older People])
      project were evaluated using a standardized comprehensive geriatric assessment
      instrument, i.e. the interResident Assessment Instrument Minimum Data Set. A
      thorough evaluation of residents' drug use, medical diagnoses and healthcare
      resource utilization was performed. A PIDP was defined according to the most
      recent update of the Beers criteria. RESULTS: Almost one out of two persons (48%)
      had at least one PIDP and almost one out of five had two or more PIDPs (18%).
      Residents with a higher number of PIDPs had a higher likelihood of being
      hospitalized. Compared with residents without PIDPs, those with two or more PIDPs
      at baseline had a higher probability of being hospitalized (hazard ratio 1.73;
      95% CI 1.14, 2.60) during the following 12 months. Risk of PIDP was positively
      associated with the total number of drugs and diseases, but negatively with age.
      PIDPs defined according to specific conditions (n = 780; 55%) were slightly more
      frequent than PIDPs based on single medications irrespective of specific
      indication (n = 639; 45%). CONCLUSIONS: PIDP is a significant problem among
      Italian NH residents. There is an urgent need for intervention trials to test
      strategies to reduce inappropriate drug use and its associated adverse health
      outcomes.

PMID- 20809665
TI  - Risk of potential drug-drug interactions among Brazilian elderly: a population
      based, cross-sectional study.
AB  - BACKGROUND: Drug-drug interactions (DDIs) are one of the main causes of adverse
      reactions related to medications, being responsible for up to 23% of hospital
      admissions. However, only a few studies have evaluated this problem in elderly
      Brazilians. OBJECTIVES: To determine the prevalence of potential DDIs (PDDIs) in
      community-dwelling elderly people in Brazil, analyse these interactions with
      regard to severity and clinical implications, and identify associated factors.
      METHODS: A population-based cross-sectional study was carried out involving 2143
      elderly (aged >or=60 years) residents of the metropolitan area of Sao Paulo,
      Brazil. Data were obtained from the SABE (Saude, Bem estar e Envelhecimento
      [Health, Well-Being, and Aging]) survey, which is a multicentre study carried out
      in seven countries of Latin America and the Caribbean, coordinated by the Pan
      American Health Organization. PDDIs were analysed using a computerized program
      and categorized according to level of severity, onset, mechanism and
      documentation in the literature. The STATA software statistical package was used
      for data analysis, and logistic regression was conducted to determine whether
      variables were associated with PDDIs. RESULTS: Analysis revealed that 568 (26.5%)
      of the elderly population included in the study were taking medications that
      could lead to a DDI. Almost two-thirds (64.4%) of the elderly population exposed
      to PDDIs were women, 50.7% were aged >or=75 years, 71.7% reported having fair or
      poor health and 65.8% took 2-5 medications. A total of 125 different PDDIs were
      identified; the treatment combination of an ACE inhibitor with a thiazide or loop
      diuretic (associated with hypotension) was the most frequent cause of PDDIs (n =
      322 patients; 56.7% of individuals with PDDIs). Analysis of the PDDIs revealed
      that 70.4% were of moderate severity, 64.8% were supported by good quality
      evidence and 56.8% were considered of delayed onset. The multivariate analysis
      showed that the risk of a PDDI was significantly increased among elderly
      individuals using six or more medications (odds ratio [OR] 3.37) and in patients
      with hypertension (OR 2.56), diabetes mellitus (OR 1.73) or heart problems (OR
      3.36). CONCLUSIONS: Approximately one-quarter of the elderly population living in
      Sao Paulo could be taking two or more potentially interacting medicines.
      Polypharmacy predisposes elderly individuals to PDDIs. More than half of these
      drug combinations (57.6%, n = 72) were part of commonly employed treatment
      regimens and may be responsible for adverse reactions that compromise the safety
      of elderly individuals, especially at home. Educational initiatives are needed to
      avoid unnecessary risks.

PMID- 20809666
TI  - Spotlight on strontium ranelate: in postmenopausal osteoporosis.
AB  - This is a review of the pharmacology of strontium ranelate (Protelos, Protos,
      Protaxos, Bivalos, Osseor), and its efficacy and tolerability in the treatment of
      patients with postmenopausal osteoporosis. Strontium ranelate is a divalent
      strontium salt of ranelic acid that is capable of increasing bone formation and
      reducing bone resorption, thereby uncoupling and rebalancing bone turnover in
      favour of bone formation. The drug is effective in reducing the risk of
      fractures, including both vertebral and nonvertebral fractures, in patients with
      postmenopausal osteoporosis, according to data from two large, double-blind,
      placebo-controlled, multicentre trials of 5 years' duration, and reduced the risk
      of hip fracture in high-risk patients in a post hoc analysis of one trial.
      Moreover, data from patients who continued to receive the drug during the 3-year
      extension phase of these trials indicate that strontium ranelate continues to
      provide protection against new vertebral fractures and nonvertebral fractures for
      up to 8 years of therapy. It also improves bone mineral density at numerous sites
      and both increases markers of bone formation and decreases markers of bone
      resorption. Strontium ranelate is administered orally as a suspension and is
      generally well tolerated. The nature of adverse events was generally similar
      regardless of treatment duration in clinical trials, with the most commonly
      reported being nausea and diarrhoea over 5 years of treatment, and memory loss
      and diarrhoea during longer-term treatment. Although an increased risk of venous
      thromboembolism was associated with strontium ranelate relative to placebo over 5
      years of treatment in a pooled analysis of clinical trials, postmarketing data
      have not confirmed this finding. Overall, the clinical data available suggest
      that strontium ranelate is an effective and generally well tolerated option for
      the first-line treatment of postmenopausal osteoporosis.

PMID- 20809667
TI  - Incretin-based therapies in the management of type 2 diabetes: rationale and
      reality in a managed care setting.
AB  - In addition to the hypoglycemia and weight gain associated with many treatments
      for type 2 diabetes, alpha-glucosidase inhibitors, thiazolidinediones, metformin,
      sulfonylureas, and the glinides do not address all of the multiple defects
      existing in the pathophysiology of the disease. Cumulatively, these oral agents
      address the influx of glucose from the gastrointestinal tract, impaired insulin
      activity, and acute beta-cell dysfunction in type 2 diabetes; however, until
      recently, there were no means to deal with the inappropriate hyperglucagonemia or
      chronic beta-cell-decline characteristic of the disease. The recently introduced
      incretin-based therapies serve to address some of the challenges associated with
      traditionally available oral antidiabetic agents. In addition to improving beta
      cell function, stimulating insulin secretion, and inhibiting glucagon secretion,
      these agents reduce appetite, thereby stabilizing weight and/or promoting weight
      loss in patients with type 2 diabetes. Of the incretin-based therapies, both the
      dipeptidyl peptidase-4 (DPP-4) inhibitors and the glucagon-like peptide-1 (GLP-1)
      receptor agonists stimulate insulin secretion and inhibit glucagon secretion. The
      subsequent review outlines evidence from selected clinical trials of the
      currently available GLP-1 receptor agonists, exenatide and liraglutide, and DPP-4
      inhibitors, sitagliptin and saxagliptin. Earlier and more frequent use of these
      incretin-based therapies is recommended in the treatment of type 2 diabetes,
      based on their overall safety and ability to achieve the glycosylated hemoglobin
      level goal. As such, both the American Diabetes Association and the American
      Association of Clinical Endocrinologists/American College of Endocrinology
      (AACE/ACE) treatment algorithms recommend the use of incretin-based therapy in
      both treatment-naive and previously treated patients. The AACE/ACE guidelines
      clearly state that these agents should not be limited to third- or fourth-line
      therapy.

PMID- 20809668
TI  - Improving treatment success rates for type 2 diabetes: recommendations for a
      changing environment.
AB  - As demonstrated by suboptimal levels of therapeutic goal achievement, there
      exists significant room for improvement in type 2 diabetes management. Despite
      widespread disease awareness and high rates of risk-factor testing in managed
      care, effective metabolic control in patients with type 2 diabetes is lacking and
      points toward a phenomenon known as clinical inertia. Clinical inertia, defined
      as a failure to initiate or advance therapy in a patient who is not at the
      evidence-based goal, is a key contributing factor in the suboptimal rates of
      therapeutic target achievement for type 2 diabetes. The causes of clinical
      inertia are multifactorial and interactive, arising among patients, providers,
      and health systems and from specific characteristics of available treatments.
      Therapeutic nonadherence is perhaps the most significant factor contributing to
      clinical inertia, with recent analyses demonstrating that providers are more
      likely to prescribe a dose escalation in patients who are adherent to therapy
      compared with those who are not. While the concept may be counterintuitive,
      antihyperglycemic agents also have the potential to cause or contribute to the
      phenomenon of clinical inertia. This often occurs via factors inherent to the
      drugs themselves, such as treatment-related adverse effects (eg, hypoglycemia,
      weight gain, edema, gastrointestinal symptoms), perception of long-term safety
      profiles, and the complexity of the treatment regimen. Often not considered, but
      equally important, is the durability of an antihyperglycemic agent to maintain
      glycosylated hemoglobin (A1C) level goals. Because no monotherapy exists to
      arrest the pancreatic beta-cell failure of type 2 diabetes, early combination
      therapy with thiazolidinediones and glucagon-like protein-1 agonists that is
      associated with sustained A1C level reduction is the only hope to change the
      progressive nature of type 2 diabetes mellitus.

PMID- 20809669
TI  - Diabetes pharmacy management: balancing safety, cost, and outcomes.
AB  - Medication nonadherence, clinical inertia, and contradictory clinical evidence on
      aggressive disease management contribute to poor outcomes in diabetes management,
      leading to increased healthcare utilization and costs. As plans increase their
      focus on the management of type 2 diabetes as an area of high healthcare resource
      utilization, the importance of appropriate antihyperglycemic agent selection is
      receiving more attention. The selection process is further complicated by the
      crowded diabetes drug category, which features several agents with diverse
      mechanisms of action and routes of administration. The choice of specific
      antihyperglycemic agents should be predicated on their effectiveness in lowering
      glucose levels, extraglycemic effects that may reduce long-term complications,
      safety profiles, tolerability, ease of use, and expense. Beyond appropriate drug
      selection, pharmacy benefit design also represents an important public health
      tool for improving treatment adherence and outcomes. Value-based benefit design,
      in particular, emphasizes high-value medical services by lowering patient copays
      to encourage plan member use. Essentially, this innovative form of benefit design
      dictates that the more clinically beneficial the therapy, the lower patients'
      cost share will be. Other interventions, such as motivational interviewing, pay
      for-performance, and medication therapy management, are also being applied to
      improve treatment adherence and outcomes in the managed care environment, with
      varying levels of success. Regardless of the specific inventions applied at
      health plans for improving treatment success in type 2 diabetes, pharmacy
      director leadership and involvement can contribute to the success of these
      efforts.

PMID- 20809670
TI  - What about compliance?

PMID- 20809671
TI  - Reconciling religious identity and reproductive practices: the Church and
      contraception in Poland.
AB  - BACKGROUND AND OBJECTIVE: After the fall of state socialism in Poland in 1989, a
      Catholic-nationalist government assumed power. The new political power of the
      Catholic Church resulted in severe restrictions on family planning (FP) services.
      Yet, Poland's fertility rate declined sharply, suggesting that women are
      controlling their fertility despite restrictions. This study examined the
      Church's influence on women's contraceptive decisions, and how women reconcile
      religious teachings with their contraceptive use. METHODS: We conducted a mixed
      methods study, including a cross-sectional survey and qualitative interviews, in
      Gdansk, Poland with sexually active women aged 18-40. The quantitative sample
      included 418 respondents; the qualitative sample included 49 respondents.
      RESULTS: Despite restrictions on FP services, modern contraceptive use among our
      sample was 56%, up from 19% in 1991. Catholicism played a relatively small role
      in respondents' contraceptive decisions; though 94.2% of respondents were
      Catholic, 79% reported that the Church had little or no influence on reproductive
      decisions. Women's explanations for how they reconcile their reproductive
      practices with Catholicism included using elements of religion to support
      contraceptive use, prioritising responsibility for family and financial
      considerations over the Church's prohibitions, and challenging the Church's
      credibility in FP matters. CONCLUSIONS: Our findings underscore women's struggles
      under post-socialist reproductive policies that limit FP access. Despite
      religious, political, and economic obstacles, contraceptive use has increased
      dramatically, indicating that FP is a high priority for women in Poland. Policies
      should respond to women's needs. Comprehensive, state-sponsored FP and sex
      education are urgently needed and the state should legitimise such services.

PMID- 20809672
TI  - Quality of the contraceptive service structure: a pilot study in Finnish health
      centre organisations.
AB  - OBJECTIVES: To evaluate the quality of the contraceptive service structure in
      health centre organisations (HCOs) in western Finland and to establish whether
      the characteristics of the HCOs are associated with the quality measured.
      METHODS: Survey data were collected from all HCOs in a university hospital area
      in western Finland (N = 63). Quality was evaluated using a score of ten
      indicators. Associations between the score and the characteristics of the HCOs
      were studied using rank correlation analysis and a multivariate ordered logit
      model. RESULTS: Among 51 HCOs yielding complete data for the evaluation, the
      quality score ranged from 3 to 10, the mean being 5.8. From 25 variables studied,
      'a chief nursing officer or leading nurse engaged in the HCO' (p = 0.001) and 'an
      appointed person responsible for management of health promotion' (p = 0.006) were
      found to be associated with a good score in the rank correlation analysis, and
      they also remained significant in multivariate analysis (Odds Ratio [OR] = 11.5,
      95% confidence interval [CI] 2.3-56.5 and OR = 5.9, 95% CI 1.6-21.5,
      respectively). CONCLUSIONS: In the majority of the HCOs involved, the quality of
      service structure was rated average, but there was much variation between the
      HCOs. The results of the multivariate analysis emphasise the importance of good
      management of services.

PMID- 20809673
TI  - Perspectives of African and Brazilian immigrant women on sexual and reproductive
      health.
AB  - OBJECTIVES: To explore attitudes and experiences related to sexual and
      reproductive health (SRH) of African and Brazilian immigrant women in Portugal.
      METHODS: Focus groups were conducted with 35 immigrant women with low income
      living in Lisbon, chosen through purposive sampling. Discussions were audio-taped
      and transcribed, and analysed through content analysis procedure. RESULTS:
      Compared to the Brazilian women, most Africans lacked knowledge and had more
      negative attitudes toward contraceptive methods, which adversely affected their
      proper use. African women were also less knowledgeable on sexually transmitted
      infections (STIs); some of them considered that their vulnerability to STIs was
      related to their partners' sexual risk behaviours. Nevertheless, a few Africans
      held less traditional attitudes toward condom use and appeared to have greater
      control over their sexual behaviour and STI prevention. Focus group discussions
      brought to light that cultural background often shapes women's desires concerning
      maternity. The participants' statements highlight the interaction between
      economic and social factors that affect immigrants and play an important role in
      their reproductive health. CONCLUSIONS: This study illustrates the importance of
      developing holistic and tailored interventions for SRH promotion among immigrant
      women, whereby the differences and specific needs of each group need to be taken
      into consideration.

PMID- 20809674
TI  - Home abortion - experiences of male involvement.
AB  - OBJECTIVE: To gain knowledge about the male partner's experience of being present
      during an induced home abortion. METHODS: Twenty-three couples, whose male
      partner had been present when the woman aborted at home, were interviewed one to
      two weeks post-abortion. RESULTS: Each of the men supported his partner in her
      decision to have a home abortion, as this gave him the possibility of being near
      and of caring for her needs on the expulsion day. All the men were present and
      all their partners confirmed that they had been supportive. Half the men had been
      anxious prior to the expulsion, but most considered that their experiences during
      the expulsion had been 'easier than expected' and their dominant feeling was one
      of relief. CONCLUSIONS: Abortion is an important life event. When taking place at
      home, it increases the possibility for the couple to share the experience.
      Sharing an abortion may have a positive impact on those men who lack a sense of
      responsibility regarding reproductive issues, such as contraceptive use. This
      could facilitate society's efforts to involve men as a target group in this
      field. Designing an abortion policy that caters for the needs of both partners is
      a challenge.

PMID- 20809676
TI  - Unintended pregnancy and prenatal care: a study from a maternity hospital in
      Turkey.
AB  - OBJECTIVES: To evaluate factors associated with pregnancy intention and its
      effects on source, content and adequacy of prenatal care for women who delivered
      in a large maternity hospital in Izmir, Turkey. METHODS: This cross-sectional
      survey was carried out using a questionnaire administered face-to-face to 351
      women who had given birth in Konak Maternity Hospital in May 2002. RESULTS:
      Nearly half (47.3%) of the pregnancies were unintended: 31.3% were mistimed, and
      16.0% unwanted. Women's and husbands' older age and lower education, lower social
      class, women's recent migration to Izmir, lower household income and absence of
      social security had a negative impact on pregnancy intention. Women with unwanted
      pregnancies had started procreating earlier; they had more pregnancies,
      deliveries, children and intentional abortions (p < 0.05). Number and contents of
      prenatal visits increased as intention status improved. When controlled for socio
      demographic variables, women with unwanted pregnancies had less prenatal care,
      received less education during prenatal visits and had less iron and vitamin
      supplementation (p < 0.05) whereas mistimed pregnancies did not significantly
      differ from intended pregnancies. CONCLUSION: Unwanted pregnancies constitute a
      risk group that should be identified early in pregnancy. Ensuring an adequate and
      satisfactory prenatal care for all requires appropriate measures to be taken by
      public health authorities.

PMID- 20809675
TI  - Teenagers' struggles with contraceptive use - what improvements can be made?
AB  - OBJECTIVE: To study the experiences of teenagers using contraceptives at an out
      patient abortion clinic and to explore the reasons behind their choices. METHODS:
      Twelve teenagers who had applied for induced abortion were interviewed three to
      four weeks after abortion. The interviews comprised open questions about
      contraceptive experiences focusing on hindrance for contraceptive use.
      Qualitative content analysis was used. RESULTS: One theme was identified:
      Struggling with feelings of uncertainty and patterns of behaviour. Three
      categories emerged from the analysis. Uncertainty dealt with decisions and
      behaviours that varied with time and between the different individuals. Factors
      that influence contraceptive use dealt with the persons that the participants had
      discussed contraceptives with, how they acquired knowledge about contraceptive
      use and the nature of their behaviour. Anxiety dealt with the side effects of
      contraception and feelings of fear related to contraceptive use. CONCLUSION: The
      participants had feelings of uncertainty, anxiety and fear towards contraceptive
      use which led to non use and inconsistent use. Guidance from health care
      providers and access to youth clinics varied and was unsatisfactory. Parents were
      supportive of contraceptive use but not active in the process of getting their
      child to initiate it. Friends and the Internet were the main sources for
      acquiring information.

PMID- 20809677
TI  - Variation in quality of care indicators for diabetes in a national sample of
      veterans and non-veterans.
AB  - BACKGROUND: Veterans have a disproportionately higher burden of type 2 diabetes.
      It is unclear whether veterans with diabetes have better self-care behaviors or
      receive better quality of care than non-veterans. The objective was to examine
      differences in diabetes care between veterans and non-veterans. METHODS: Data
      analysis was performed with respondents from the 2003 Behavioral Risk Factor
      Surveillance Survey (n = 21,111 with diabetes). Veterans were those who reported
      U.S. military service and no longer on active duty. Self-care behaviors included
      daily fruit and vegetable intake, physical activity level, self-foot checks, and
      home glucose testing. Quality of care indicators included provider actions over
      the past 12 months (2+ office visits, 2+ glycosylated hemoglobin checks, 1+ foot
      exams, 1+ dilated eye exams, daily aspirin use, receiving flu or pneumonia
      vaccine). Multiple logistic regression using STATA version 10 (Stata Corp.,
      College Station, TX) analyzed differences by veteran status on each quality
      indicator, controlling for sociodemographics and diabetes education. RESULTS:
      Veterans comprised 14.2% of the sample, and 12.4% had diabetes compared to 6.7%
      of non-veterans. In final adjusted models, veterans were significantly more
      likely to check their feet (odds ratio [OR] 1.33, 95% confidence interval [CI]
      1.09, 1.64), get a dilated eye exam (OR 1.36, 95% CI 1.11, 1.66), receive aspirin
      (OR 1.31, 95% CI 1.04, 1.65), get a flu shot (OR 1.32, 95% CI 1.09, 1.61), and
      ever get a pneumonia shot (OR 1.38, 95% CI 1.12, 1.70). CONCLUSIONS: Veterans
      appear to have better self-care behaviors and receive better preventive care than
      non-veterans. However, future efforts need to focus on boosting self-care to
      improve diabetes outcomes.

PMID- 20809678
TI  - Inter-day glycemic variability assessed by continuous glucose monitoring in
      insulin-treated type 2 diabetes patients on hemodialysis.
AB  - BACKGROUND: Type 2 diabetes patients on chronic hemodialysis have a high
      prevalence of cardiovascular complications and often show a poor glycemic
      control. Single-spot glycemic measurements are not always meaningful, and the
      hemoglobin A1c (HbA1c) value does not reflect short-term variations in glucose
      metabolism in this patient category. Therefore, to better understand their
      metabolic balance, we studied a group of diabetes patients on hemodialysis by a
      continuous glucose monitoring (CGM) system. METHODS: Twelve insulin-treated type
      2 diabetes patients on hemodialysis were studied by a microdialysis-based
      subcutaneous glucose sensor over a period of 2 days, including the dialysis day
      (HD) and the following inter-dialytic period ("free" day [FD]). RESULTS: The mean
      24-h glycemic value, the mean amplitude of glucose excursions, and the SD of mean
      glucose were significantly higher in the HD than the FD (186 +/- 50 vs. 154 +/-
      25 mg/dL, P<0.05; 75 +/- 22 vs. 56 +/- 15 mg/dL, P<0.05; and 57 +/- 6 vs. 35 +/-
      11 mg/dL, P<0.05, respectively). Considering the 48-h recording, there was a
      direct correlation between the mean glucose concentration and the HbA1c (r=0.47,
      P<0.05), whereas no association was observed between the measures of glucose
      variability and HbA1c. CONCLUSIONS: Insulin-treated diabetes patients on
      hemodialysis showed different glucose profiles between the HD and the FD. In
      particular, in the HD they have had an increased glycemic variability, which may
      represent an adjunctive risk factor for cardiovascular complications. Therefore
      the use of a CGM system, as a means of assessing the measures of glycemic
      variability, could improve the management of insulin therapy in these patients.

PMID- 20809679
TI  - Detrended fluctuation analysis is considered to be useful as a new indicator for
      short-term glucose complexity.
AB  - BACKGROUND: This study clarified whether detrended fluctuation analysis (DFA) can
      evaluate how to advance the loss of complexity from impaired glucose tolerance
      (IGT) through mild diabetes mellitus (DM) to overt DM. METHODS: Continuous
      glucose monitoring (CGM) was done during a 48-h interval for 59 subjects from
      multiple centers. Subjects were divided according to CGM data into those with
      impaired glucose tolerance (IGT) (n = 20), mild DM (n = 13), and overt DM (n =
      26). The short-term (alpha1) and long-term (alpha2) range exponentials by DFA
      were compared among the three groups. RESULTS: The value of alpha1 within 1h was
      significantly lower in the IGT group than in either of the other two groups (IGT
      vs. mild DM vs. overt DM, 1.53 +/- 0.22 vs. 1.71 +/- 0.17 vs. 1.77 +/- 0.13,
      P<0.0001), and alpha1 within 2h differed significantly among the three groups
      (1.49 +/- 0.13 vs. 1.57 +/- 0.10 vs. 1.72 +/- 0.10, P<0.0001). The alpha1 within
      3h was significantly higher in overt DM than in either of the other two groups
      but did not change between IGT and mild DM (1.44 +/- 0.12 vs. 1.52 +/- 0.11 vs.
      1.67 +/- 0.09, P<0.0001). All short-term exponents decreased gradually but
      significantly as the window widened in all groups (P<0.0001). The alpha2 over 1h
      was significantly higher in overt DM but was unchanged in IGT and mild DM (1.22
      +/- 0.11 vs. 1.27 +/- 0.12 vs. 1.36 +/- 0.13, P = 0.0010). The alpha2 over 3h did
      not differ among the three groups. CONCLUSIONS: Progressive loss of complexity in
      the glycemic profile occurred from the short-term range and spread to the long
      term range concomitantly with the progression of the DM state.

PMID- 20809680
TI  - Effects of bile salts on the lovastatin pharmacokinetics following oral
      administration to rats.
AB  - This study aimed to examine the effects of bile salts on pharmacokinetics of
      lovastatin, which has low bioavailability. Lovastatin solid dispersions were
      prepared using sodium deoxycholate (NaDC) and sodium glycholate (NaGC) at ratios
      of 1:19, 1:49, and 1:69. The formulated solid dispersions and control (commercial
      tablet) were administered to rats and plasma concentrations were determined by a
      validated LC-MS/MS method. Statistically significant differences were found in
      C(max), AUC0-10, and AUC0-infinity values among lovastatin formulations (p <
      0.05). NaDC-containing formulations revealed higher bioavailabilities than NaGC
      containing solid dispersions at ratios of 1:19 and 1:49. Especially, NaDC
      containing formulation at a ratio of 1:19 (NaDC19) showed the highest
      bioavailability. The AUC (both AUC0-10 and AUC0-infinity) of NaDC19 was
      statistically higher than control and NaDC69 (p < 0.05). The AUC values decreased
      as bile salt concentrations increased. Overall, formulations containing bile
      salts showed higher AUC values than control, even though all formulations did not
      show significantly higher AUC. In conclusion, the addition of bile salts to
      lovastatin could enhance drug bioavailabilities. However, too high concentrations
      of bile salts could decrease bioavailabilities of lovastatin.

PMID- 20809681
TI  - Analysis of hemodialysis-associated hypoglycemia in patients with type 2 diabetes
      using a continuous glucose monitoring system.
AB  - BACKGROUND: Adequate glycemic control is important for patients with end-stage
      renal disease on maintenance hemodialysis (HD). Continuous glucose monitoring
      (CGM) systems are reported as a useful method for glucose monitoring in patients
      under maintenance HD. The object of this study was to describe glucose profiles
      and hypoglycemia associated with HD in diabetes patients using a CGM system.
      METHODS: We recruited nine medically stable patients with type 2 diabetes under
      maintenance HD. CGMS System Gold (Medtronic MiniMed, Northridge, CA) was applied
      to the subjects for 144 h. During the period, HD using glucose-containing
      dialysate was performed every other day. Various glucose profiles were calculated
      from the CGM readings and compared between the day on and the day off dialysis.
      RESULTS: Mean +/- SD for age, duration of diabetes, and hemoglobin A1c were 67 +/
      9 years, 24 +/- 9 years, and 8.6 +/- 1.2%, respectively. Hemoglobin A1c was
      correlated with mean glucose (rho = 0.780, P < 0.05) and with area under the
      curve for glucose above 180 mg/dL (rho = 0.797, P<0.05). Although there was no
      difference for mean amplitude of glycemic excursion between the day on and off
      HD, hypoglycemia occurred predominantly with day on HD. In the subjects who
      maintained antidiabetes agents with day on HD, glucose levels decreased with
      initiation of HD, causing significantly lower glucose levels compared to those
      during the equivalent time of the following day without HD. CONCLUSIONS:
      According to the CGM system, glucose variability was not affected by HD. However,
      in spite of glucose-containing dialysate, HD seemed to increase the risk of
      hypoglycemia.

PMID- 20809682
TI  - Lower rate of initial failures and reduced occurrence of adverse events with a
      new catheter model for continuous subcutaneous insulin infusion: prospective, two
      period, observational, multicenter study.
AB  - BACKGROUND: No recent clinical data on the incidence of catheter-related adverse
      events under insulin pump therapy have been reported. METHODS: This was a
      prospective, two-period, observational, multicenter study in 45 diabetes
      outpatients (mean continuous subcutaneous insulin infusion [CSII] use, 6 years;
      mean hemoglobin A1c, 7.7%, at baseline). During the initial 1-month period (P1),
      the patients used their current catheter model, including a soft cannula in 98%
      of cases. They moved then to the new Accu-Chek FlexLink catheter model
      (Disetronic Medical Systems AG, Burgdorf, Switzerland) for a 3-month period. The
      primary end point, including insertion failures and unexplained hyperglycemia
      within the first 6h after catheter placement, was assessed from logbook records
      during P1 and the last month of the second period (P2). Secondary end points were
      catheter replacements for unexplained hyperglycemia and/or events at risk for
      immediate insulin delivery failure after the first 6h. RESULTS: Forty-five
      initial infusion failures occurred in 14 patients among 507 catheter insertions
      (8.9% of cases) during P1, whereas 15 similar events were seen in nine patients
      during P2 among 488 catheter insertions (3.1% of cases) (P<0.001). Catheters were
      replaced for later infusion troubles in 8% of cases during both P1 and P2. The
      overall rate of late cumulative events was, however, 113 of 507 (P1) versus 66 of
      488 (P2) (P<0.001). The occurrence of pain, skin reaction, or redness at the
      infusion site was lower during P2. CONCLUSION: Incidences both of initial
      failures and of premature catheter replacements were 8-9% with current CSII
      catheters. Significantly reduced failures after insertion and adverse events at
      the infusion site were observed with the new catheter model.

PMID- 20809683
TI  - The fallacy of hindsight: response to Moses and Koenen.

PMID- 20809684
TI  - Association of interleukin-10 polymorphisms with cytokines in type 2 diabetic
      nephropathy.
AB  - OBJECTIVE: Interleukin-10 (IL-10) polymorphic variants are linked with cytokine
      production and are involved in many chronic inflammatory diseases, including type
      2 diabetes mellitus (T2DM). We investigated the hypothesis that IL-10 promoter
      polymorphisms may be associated with cytokine expressions involved in the
      progression of diabetic nephropathy (DN). STUDY DESIGN: A total of 72 Taiwanese
      subjects were included in this study; along with a control group, patients had a
      diagnosis of DN lasting >=2 years, and patients had a diagnosis of T2DM with
      normal renal functions lasting >=5 years. Their IL-10 and tumor necrosis factor
      alpha (TNF-alpha) genotyping and association of blood chemistry, plasma IL-10,
      TNF-alpha, and monocyte chemoattract protein-1 (MCP-1), and urinary MCP-1 were
      investigated. RESULTS: The IL-10-(-592) genotype exhibited significant
      association with cytokine expressions in DN: significantly higher TNF-alpha and
      lower plasma IL-10 levels were observed in IL-10-(-592)AA, whereas a higher urine
      MCP-1 level was found in Taiwanese patients with the IL-10-(-592)CC genotype.
      CONCLUSIONS: IL-10-(-592) promoter polymorphisms may influence IL-10 and MCP-1
      production, which may be an indicator of nephropathy risk in Taiwanese T2DM
      patients.

PMID- 20809685
TI  - To flow or not to flow - a matter of life and death.

PMID- 20809686
TI  - Incidence of rearrest after return of spontaneous circulation in out-of-hospital
      cardiac arrest.
AB  - BACKGROUND: Return of spontaneous circulation (ROSC) occurs in 35.0 to 61.0% of
      emergency medical services (EMS)-treated out-of-hospital cardiac arrests (OHCAs);
      however, not all patients achieving ROSC survive to hospital arrival or
      discharge. Previous studies have estimated the incidence of some types of
      rearrest(RA) at 61.0 to 79.0%, and the electrocardiogram (ECG) waveform
      characteristics of prehospital RA rhythms have not been previously described.
      OBJECTIVES: We sought to determine the incidence of RA in OHCA, to classify RA
      events by type, and to measure the time from ROSC to RA. We also conducted a
      preliminary analysis of the relationship between first EMS-detected rhythms and
      RA, as well as the effect of RA on survival. METHODS: The Pittsburgh Regional
      Clinical Center of the National Heart, Lung, and Blood Institute (NHLBI) 
      sponsored Resuscitation Outcomes Consortium (ROC) provided cases from a
      population-based cardiac arrest surveillance program, ROC Epistry. Only OHCA
      cases of nontraumatic etiology with available and adequate ECG files were
      included. We analyzed defibrillator-monitor ECG tracings (Philips MRX), patient
      care reports (PCRs), and defibrillator audio recordings from EMS-treated cases of
      OHCA spanning the period from October 2006 to December 2008. We identified ROSC
      and RA through interpretation of ECG tracings and audio recordings. Rearrest
      events were categorized as ventricular fibrillation (VF), pulseless ventricular
      tachycardia (VT), asystole, and pulseless electrical activity (PEA) based on ECG
      waveform characteristics. Proportions of RA rhythms were stratified by first EMS
      rhythm and compared using Pearson's chi-square test. Logistic regression was used
      to test the predictive relationship between RA and survival to hospital
      discharge. RESULTS: Return of spontaneous circulation occurred in 329 of 1,199
      patients (27.4% [95.0% confidence interval (CI): 25.0-30.0%]) treated for cardiac
      arrest. Of these, 113 had ECG tracings that were available and adequate for
      analysis. Rearrest occurred in 41 patients (36.0% [95.0% CI: 26.0-46.0%]), with a
      total of 69 RA events. Survival to hospital discharge in RA cases was 23.1%
      (95.0% CI: 11.1-39.3%), compared with 27.8% (95.0% CI: 17.9-39.6%) in cases
      without RA. Counts of RA events by type were as follows: 17 VF (24.6% [95% CI:
      15.2-36.5%]), 20 pulseless VT (29.0% [95.0% CI: 18.7-41.2%]), 26 PEA (37.0%
      [95.0% CI: 26.3-50.2%]), and six asystole (8.8% [95.0% CI: 3.3-18.0%]). Rearrest
      was not predictive of survival to hospital discharge; however, initial EMS rhythm
      was predictive of RA shockability. The overall median (interquartile range) time
      from ROSC to RA among all events was 3.1 (1.6-6.3) minutes. CONCLUSION: In this
      sample, the incidence of RA was 38.0%. The most common type of RA was PEA.
      Shockability of first EMS rhythm was found to predict subsequent RA rhythm
      shockability.

PMID- 20809687
TI  - Effectiveness of morphine, fentanyl, and methoxyflurane in the prehospital
      setting.
AB  - OBJECTIVE: To compare the effectiveness of intravenous (IV) morphine, intranasal
      (IN) fentanyl, and inhaled methoxyflurane when administered by paramedics to
      patients with moderate to severe pain. METHODS: We conducted a retrospective
      comparative study of adult patients with moderate to severe pain treated by
      paramedics from the Ambulance Service of New South Wales who received IV
      morphine, IN fentanyl, or inhaled methoxyflurane either alone or in combination
      between January 1, 2004, and November 30, 2006. We used multivariate logistic
      regression to analyze data extracted from a clinical database containing
      routinely entered information from patient health care records. The primary
      outcome measure was effective analgesia, defined as a reduction in pain severity
      of > or = 30% of initial pain score using an 11-point verbal numeric rating scale
      (VNRS-11). RESULTS: The study population comprised 52,046 patients aged between
      16 and 100 years with VNRS-11 scores of > or = 5. All analgesic agents were
      effective in the majority of patients (81.8%, 80.0%, and 59.1% for morphine,
      fentanyl, and methoxyflurane, respectively). There was very strong evidence that
      methoxyflurane was inferior to both morphine and fentanyl (p < 0.0001). There was
      strong evidence that morphine was more effective than fentanyl (p = 0.002). There
      was no evidence that combination analgesia was better than either fentanyl or
      morphine alone. CONCLUSION: Inhaled methoxyflurane, IN fentanyl, and IV morphine
      are all effective analgesic agents in the out-of-hospital setting. Morphine and
      fentanyl are significantly more effective analgesic agents than methoxyflurane.
      Morphine appears to be more effective than IN fentanyl; however, the benefit of
      IV morphine may be offset to some degree by the ability to administer IN fentanyl
      without the need for IV access.

PMID- 20809688
TI  - Variation in emergency medical services workplace safety culture.
AB  - INTRODUCTION: Workplace attitude, beliefs, and culture may impact the safety of
      patient care. This study characterized perceptions of safety culture in a
      nationwide sample of emergency medical services (EMS) agencies. METHODS: We
      conducted a cross-sectional survey involving 61 advanced life support EMS
      agencies in North America. We administered a modified version of the Safety
      Attitudes Questionnaire (SAQ), a survey instrument measuring dimensions of
      workplace safety culture (Safety Climate, Teamwork Climate, Perceptions of
      Management, Job Satisfaction, Working Conditions, and Stress Recognition). We
      included full-time and part-time paramedics and emergency medical technicians. We
      determined the variation in safety culture scores across EMS agencies. Using
      hierarchical linear models, we determined associations between safety culture
      scores and individual and EMS agency characteristics. RESULTS: We received 1,715
      completed surveys from 61 EMS agencies (mean agency response rate 47%; 95%
      confidence interval [CI] 10%, 83%). There was wide variation in safety culture
      scores across EMS agencies [mean (minimum, maximum)]: Safety Climate 74.5 (min
      49.9, max 89.7), Teamwork Climate 71.2 (min 45.1, max 90.1), Perceptions of
      Management 67.2 (min 31.1, max 92.2), Job Satisfaction 75.4 (min 47.5, max 93.8),
      Working Conditions 66.9 (min 36.6, max 91.4), and Stress Recognition 55.1 (min
      31.3, max 70.6). Air medical EMS agencies tended to score higher across all
      safety culture domains. Lower safety culture scores were associated with
      increased annual patient contacts. Safety Climate domain scores were not
      associated with other individual or EMS agency characteristics. CONCLUSION: In
      this sample, workplace safety culture varies between EMS agencies.

PMID- 20809689
TI  - A model for the association of the call volume and the unavailable-for-response
      interval on the delayed ambulance response for out-of-hospital cardiac arrest
      using a geographic information system.
AB  - BACKGROUND: An optimal ambulance response interval is desirable for emergency
      medical services (EMS) operations. Arriving on scene within a treatment time
      window is often delayed for many reasons, including overwhelming call volume.
      OBJECTIVE: To determine whether an association exists between the ambulance call
      volume (ACV), the unavailable-for-response (UFR) interval, and the delayed
      ambulance response for out-of-hospital cardiac arrest (OHCA) patients. METHODS:
      This was a retrospective observational study conducted in Seoul, Republic of
      Korea. The EMS ambulance logs from the metropolitan city's 22 EMS agencies, from
      January 1, 2006, to June 30, 2007, were obtained from the National Emergency
      Management Agency. These data included patient demographics and call location
      addresses. The addresses of the call locations and ambulance stations were
      geocoded and configured with a polygon expressing the optimal coverage areas in
      which an ambulance could travel within 4 minutes from their base station. The
      median ACV and mean UFR interval of each EMS agency were calculated. An actual
      response time interval greater than 4 minutes compared with the optimal coverage
      area was defined as a suboptimal response. Potential influencing factors on
      suboptimal response were analyzed using a multivariate logistic regression model
      to calculated the odds ratio (OR) and 95% confidence interval (95% CI). RESULTS:
      Geocoding was successful for 255,961 calls, and 3,644 cardiac arrests occurred
      within the configured optimal response coverage areas. The response rate
      intervals for cardiac arrest patients, however, were optimal in only 22.6% of
      calls. Influencing factors for suboptimal response (occurring in 77.4% of the
      cases) were the median ACV and the mean UFR interval of each EMS agency. When the
      median ACV was seven or more, the OR of suboptimal response was 1.407 (1.142
      1.734). If the mean UFR interval was 55 minutes or more, the OR for suboptimal
      response was 1.770 (1.345-2.329). CONCLUSION: The ambulance response time
      intervals in this study setting were associated with EMS agencies with higher
      ACVs and longer UFR intervals.

PMID- 20809690
TI  - A meta-analysis of prehospital airway control techniques part II: alternative
      airway devices and cricothyrotomy success rates.
AB  - BACKGROUND: Airway management is a key component of prehospital care for
      seriously ill and injured patients. Oral endotracheal intubation (OETI) is the
      definitive airway of choice in most emergency medical services (EMS) systems.
      However, OETI may not be an approved skill for some clinicians or may prove
      problematic in certain patients because of anatomic abnormalities, trauma, or
      inadequate relaxation. In these situations alternative airways are frequently
      employed. However, the reported success rates for these devices vary widely, and
      established benchmarks are lacking. OBJECTIVE: We sought to determine pooled
      estimates of the success rates of alternative airway devices (AADs) and needle
      cricothyrotomy (NCRIC) and surgical cricothyrotomy (SCRIC) placement through a
      meta-analysis of the literature. METHODS: We performed a systematic literature
      search for all English-language articles reporting success rates for AADs, SCRIC,
      and NCRIC. Studies of field procedures performed by prehospital personnel from
      any nation were included. All titles were reviewed independently by two authors
      using prespecified inclusion criteria. Pooled estimates of success rates for each
      airway technique were calculated using a random-effects meta-analysis model.
      RESULTS: Of 2,005 prehospital airway titles identified, 35 unique studies were
      retained for analysis of AAD success rates, encompassing a total of 10,172
      prehospital patients. The success rates for SCRIC and NCRIC were analyzed across
      an additional 21 studies totaling 512 patients. The pooled estimates (and 95%
      confidence intervals [CIs]) for intervention success across all clinicians and
      patients were as follows: esophageal obturator airway-esophageal gastric tube
      airway (EOA-EGTA) 92.6% (90.1%-94.5%); pharyngeotracheal lumen airway (PTLA)
      82.1% (74.0%-88.0%); esophageal-tracheal Combitube (ETC) 85.4% (77.3%-91.0%);
      laryngeal mask airway (LMA) 87.4% (79.0%-92.8%); King Laryngeal Tube airway (King
      LT) 96.5% (71.2%-99.7%); NCRIC 65.8% (42.3%-83.59%); and SCRIC 90.5% (84.8%
      94.2%). CONCLUSIONS: We provide pooled estimates for prehospital AAD, NCRIC, and
      SCRIC airway interventions. Of the AADs, the King LT demonstrated the highest
      insertion success rate (96.5%), although this estimate is based on limited data,
      and data regarding its ventilatory effectiveness are lacking; more data are
      available for the ETC and LMA. The ETC, LMA, and PTLA all had similar-but lower
      success rates (82.1%-87.4%). NCRIC has a low rate of success (65.8%); SCRIC has a
      much higher success rate (90.5%) and should be considered the preferred
      percutaneous rescue airway.

PMID- 20809692
TI  - Death notification training for prehospital providers: a pilot study.
AB  - BACKGROUND: When cardiac arrest occurs at home, family members are likely to be
      present during resuscitation efforts. However, little training is provided to
      prehospital providers on how to best manage a family-witnessed resuscitation
      (FWR) and deliver the news of death in the field. OBJECTIVE: To study the
      feasibility and utility of an educational intervention designed to improve
      prehospital provider comfort with FWR and death notification. METHODS: This was a
      pilot study of a convenience sample of 45 prehospital providers who participated
      in an educational lecture, with 20 providers then attending a small-group
      standardized death-notification encounter. Descriptive statistics were calculated
      to assess pre- and postintervention attitudes and knowledge with respect to FWR
      and death notification. RESULTS: All subjects had participated in at least one
      cardiac arrest resuscitation effort, with 28 (62.2%) having performed a death
      notification. Seventy-one percent (n = 32) of the participants have continued
      resuscitation efforts despite futility because the family was present. Fifty-five
      percent of participants (n = 25) had an interest in improving their FWR and death
      notification skills. After the educational seminar, 61.2% (n = 19) of all
      participants correctly answered at least five of the six knowledge-based
      questions. The small-group intervention participants showed an overall
      improvement in death notification skills, with a majority expressing confidence
      in their ability to effectively communicate with families during an unsuccessful
      resuscitation. CONCLUSION: This pilot study suggests that a short educational
      intervention can impact prehospital providers' comfort with death notification.
      Future research will need to be conducted on prehospital provider skill retention
      and the impact this training has on family members.

PMID- 20809691
TI  - Awareness and utilization of emergency medical services by limited English
      proficient caregivers of pediatric patients.
AB  - BACKGROUND: Previous studies have shown that limited-English-proficient (LEP)
      patients are less likely to utilize health care services. Objective. To assess
      the knowledge and perceived barriers to utilization of emergency medical services
      (EMS) by LEP caregivers of children served by an urban EMS system. METHODS: We
      prospectively surveyed a convenience sample of caregivers of children presenting
      to the emergency department (ED) from January to December 2008. Caregivers were
      identified as LEP using their response to the U.S. Census question ;;How well do
      you speak English?'' Caregivers were assigned to one of three cohorts: 1) LEP
      Spanish- and Arabic-speaking caregivers (n = 50), 2) proficient-in-English (PE)
      Spanish- and Arabic-speaking caregivers (n = 50), and (3) native English-speaking
      (NES) caregivers (n = 100). We collected data on EMS awareness and perceived
      barriers to EMS utilization using a written survey administered in the
      caregivers' preferred language (English, Spanish, or Arabic). We used descriptive
      methods to summarize sample characteristics and comparative methods (chi-square
      test, analysis of variance [ANOVA], and t-test) to compare group differences.
      RESULTS: There were no differences in the patient age groups, triage categories,
      caregiver age, and payer status among the three groups. The LEP caregivers were
      less aware of EMS (93% NES vs. 94% PE vs. 60% LEP; p < 0.01) and had called EMS
      significantly fewer times when compared with the NES and PE groups (16% LEP vs.
      58% NES vs. 48% PE; p < 0.01). Fourteen percent of the LEP caregivers were
      unaware of the telephone number to call for EMS. Concerns about inability to
      communicate with the operator and cost were cited by the LEP caregivers as the
      main barriers to EMS utilization. CONCLUSIONS: Caregivers with limited English
      proficiency are less aware of and are less likely to utilize EMS for their
      children. Barriers to utilization include concerns of cost and communication with
      the operator.

PMID- 20809693
TI  - Role of emergency medical services in disaster response.
AB  - This is the official position statement of the National Association of EMS
      Physicians on the role of emergency medical services (EMS) in disaster response.

PMID- 20809694
TI  - Medical direction for operational emergency medical services programs.
AB  - This is the official position statement of the National Association of EMS
      Physicians and the National Association of State EMS Officials on medical
      direction for operational emergency medical services (EMS) programs.

PMID- 20809695
TI  - New strategies for anterior cruciate ligament partial rupture using bone marrow
      transplantation in rats.
AB  - The purpose of this study was to compare anterior cruciate ligament (ACL)
      regeneration between animal groups subjected to intra-articular injection of
      fresh whole bone marrow cells (BMCs), cultured mesenchymal stem cells (MSCs), or
      saline. Partially transected ACLs in Fischer 344/Nslc rats were prepared,
      followed by injection of BMCs, MSCs, or saline into the articular cavity at 1
      week after transection. Donor cells expressing green fluorescent protein were
      detected in the recipient's transected ACLs at 4 weeks in the BMC and MSC groups,
      and their ACLs appeared almost normal histologically. Further, there were
      significantly more mature spindle cells in the BMC group than in the saline group
      at 4 weeks. Biomechanically, the tensile strength in the BMC group reached near
      normal levels at 4 weeks after injection. The levels of transforming growth
      factor-beta1 in the ACL tissue and knee joint fluid in the BMC group were
      increased significantly compared with that of the saline group at 4 weeks as
      detected by immunohistochemical analysis. In conclusion, intra-articular bone
      marrow transplantation using fresh whole BMCs is an effective treatment for ACL
      partial rupture. This therapy is easy to apply in a clinical setting because no
      culture system is required for collecting MSCs.

PMID- 20809696
TI  - Amaranthus leucocarpus lectin (ALL) enhances anti-CD3-dependent activation of
      murine T cells and promotes cell survival.
AB  - The Galbeta1,3GalNAc-specific lectin from Amaranthus leucocarpus (ALL) shows a
      differential binding pattern on murine thymocytes, peripheral and activated
      CD4(+) and CD8(+) T cells. Although ALL detects activation-related changes in T
      cell surface carbohydrate moieties, no study has been performed to examine the
      effect of ALL on T cell activation. In this study, we analyzed the anti-CD3
      dependent activation of murine T cells in the presence of ALL by measuring
      proliferation, surface activation marker expression, and IL-2 secretion using
      total cells from the lymph node. The results showed that ALL did not
      significantly induce T cell activation but did enhance anti-CD3-dependent
      activation of both CD4(+) and CD8(+) T cells. In addition, ALL protected T cells
      from spontaneous apoptosis and increased cell survival in serum-free culture
      conditions. Our findings indicate that ALL alone does not affect T cell
      activation, but do suggest that ALL has an anti-CD3-dependent co-stimulatory-like
      effect on T cell activation. Moreover, ALL promotes cell survival in regular and
      serum-free culture conditions. This study is the first report of a non-mitogenic
      T cell-binding lectin that can induce a possible costimulatory-like effect and
      provides a new tool for understanding how glycosylation impacts the T cell
      response.

PMID- 20809697
TI  - Rapid determination of clenbuterol in urine by a competitive bead immunoassay
      based on Luminex technology.
AB  - A new competitive bead immunoassay (CBIA) based on Luminex technology for
      detecting clenbuterol in urine was reported. The carboxylated fluorescent beads
      were directly coated with clenbuterol derivatives without carrier protein spacer.
      Clenbuterol antibody was biotinylated, which was used for clenbuterol detection
      in combination with the functionalized bead and streptavidin-phycoerythrin
      (SAPE). The effects of spacer on the CBIA method were investigated. The results
      indicated that the presence of small molecular spacer between bead and hapten
      improved the assay sensitivity and the hydrophilic spacer (glycine) was better
      than the hydrophobic spacer (m-aminobenzoic acid) for this CBIA method. The study
      affirms the importance of the judicious choice of hapten derivatives in the CBIA
      method for detecting small molecule drug based on Luminex technology. The method
      could be used for clenbuterol detection in livestock urine and possible for the
      simultaneous detection of multiple veterinary drugs.

PMID- 20809698
TI  - Circulating regulatory T cells in endometrial cancer: a role for age and
      menopausal status.
AB  - Regulatory T cells (Treg) are a sub-population of T cells that suppress self
      reactivity and are implicated in immune tolerance towards malignant cells.
      Circulating Treg cells are increased in several cancers. In endometrial cancer
      Treg cells have been investigated only in tumour tissues and, in contrast to some
      other tumours, fewer Treg cells were reported in endometrial cancer compared with
      benign controls. Flow cytometry was used to determine the frequency of
      circulating Treg cells in women undergoing hysterectomy for either endometrial
      cancer (n = 24) or non- cancer-related conditions (n = 21). Circulating Treg
      cells were more abundant in women with cancer compared to those without (4.68%
      vs. 3.66%, p = 0.05, Mann-Whitney test). This relationship disappeared, however,
      when only data from post-menopausal women were included in the analysis. Mean
      Treg cell frequency was 4.65% in postmenopausal women with cancer (n = 23) and
      4.73% in postmenopausal controls (n = 5) (p = 0.9). In women without cancer we
      found that mean Treg cell frequency was higher in postmenopausal women (4.73%, n
      = 5) in comparison to premenopausal controls (3.33%, n = 16) (p = 0.02). These
      results suggest that the increased proportion of Treg cells seen in endometrial
      cancer patients might be, at least in part, attributed to their postmenopausal
      status or age.

PMID- 20809699
TI  - Characterized polysaccharides from black soybean induce granulocyte colony
      stimulated factor gene expression in a phosphoinositide 3-kinase-dependent
      manner.
AB  - Black soybean (Glycine max L. merr.) is an edible Chinese medicine for
      nourishment spleen. In the present study, effects of characterized
      polysaccharides from black soybean (PGM) on granulocyte colony-stimulated factor
      (G-CSF) production in human peripheral blood mononuclear cells (PBMC) were
      determined and their action mechanisms were examined. The results indicated that
      PGM concentration-dependently enhanced G-CSF production in PBMC through
      modulation of mRNA expression. Data from Western blotting showed that PGM
      significantly induced the extracellular signal-regulated protein kinase (ERK)
      activation in PBMC. The nuclear factor (NF)-kappaB activation in PBMC was
      increased with PGM by modulation of IkappaB degradation and PKC theta activation.
      The levels of G-CSF mRNA in PGM-treated PBMC could be reduced by ERK inhibitor
      U0126 and NF-kappaB inhibitor pyrrolidine dithiocarbamate, respectively.
      Furthermore, the data showed that PGM stimulated phosphoinositide 3-kinase (PI3K)
      regulated Akt phosphorylation. The PI3K inhibitor, Ly294002, blocked ERK, NF
      kappaB, and PKC theta activation and G-CSF mRNA expression in PBMC induced by
      PGM. Thus, we first proved that the enhancement mechanisms of PGM on G-CSF
      production, appeared to be mediated, at least in part, through activation of
      PI3K, ERK, PKC theta, and NF-kappaB signaling pathways in PBMC. We suggest that
      PGM from black soybean is a potential G-CSF stimulator.

PMID- 20809700
TI  - Evaluation of interleukin-8 in hepatitis C virus infection: relation to combined
      peg-interferon ribavirin response and genotype 4.
AB  - Hepatitis C virus (HCV), a major cause of liver disease worldwide, is frequently
      resistant to the antiviral alpha interferon (IFN). Previous studies have shown
      that HCV NS5A protein induces expression of the proinflammatory interleukin-8 (IL
      8) and this may affect the therapeutic outcome. The aim of the present study was
      to investigate the relationship among levels of IL-8 in serum of subjects with
      past exposure to HCV indicated by positive IgG to HCV and negative PCR, patients
      with chronic HCV infections and in responder to combined alfa IFN and ribavirin
      therapy. The study included 48 Egyptian subjects with evidence of HCV infection.
      They were classified according to viremia to patients with chronic hepatitis C
      with positive viremia and immune subjects with positive HCV IgG alone. Chronic
      HCV patients were followed after therapy and 16 healthy adults as control group.
      It was found that viral load was dependent factor for the level of IL 8 (P =
      0.003) and there was significant correlation between levels of IL-8 before
      treatment and after treatment. The present study highlights the kinetic of serum
      levels of interleukin-8 in patients with chronic hepatitis C genotype 4 before
      and after therapy with combined alfa interferon and ribavirin. It was
      demonstrated that HCV infection was associated with higher levels of interleukin
      8 in pretreatment and posttreatment period. Moreover, immune subjects also had
      higher level of interleukin-8, indicating its role in immunity to HCV infection.

PMID- 20809701
TI  - Do psychological variables mediate sex differences in young adults' alcohol use?
AB  - This study applied an extended theory of planned behavior to test whether
      psychological variables mediate sex differences in alcohol consumption in social
      contexts. Questionnaires of 300 young adults (urban, mean age 25 years, 49%
      female) were collected in 2007 prior to a sociable drinking occasion; consumption
      data were obtained through telephone interviews thereafter. The multiple-path
      mediation model was analyzed using structural equation modeling. Sex differences
      in alcohol consumption, which were considerable, were partly mediated by the
      significant specific indirect effects of subjective norms through intention and
      of self-efficacy through both intention and willingness. Body weight was not a
      significant mediator. Limitations are noted and implications for future research
      are discussed.

PMID- 20809702
TI  - Erythropoietin and prenatal hypoxia-ischemia.

PMID- 20809704
TI  - Posthemorrhagic ventricular dilation.

PMID- 20809703
TI  - Postnatal erythropoietin treatment mitigates neural cell loss after systemic
      prenatal hypoxic-ischemic injury.
AB  - OBJECT: Brain injury from preterm birth predisposes children to cerebral palsy,
      epilepsy, cognitive delay, and behavioral abnormalities. The CNS injury often
      begins before the early birth, which hinders diagnosis and concurrent treatment.
      Safe, effective postnatal interventions are urgently needed to minimize these
      chronic neurological deficits. Erythropoietin (EPO) is a pleiotropic
      neuroprotective cytokine, but the biological basis of its efficacy in the damaged
      developing brain remains unclear. Coordinated expression of EPO ligand and
      receptor expression occurs during CNS development to promote neural cell
      survival. The authors propose that prenatal third trimester global hypoxia
      ischemia disrupts the developmentally regulated expression of neural cell EPO
      signaling, and predisposes neural cells to death. Furthermore, the authors
      suggest that neonatal exogenous recombinant human EPO (rhEPO) administration can
      restore the mismatch of EPO ligand and receptor levels, and enhance neural cell
      survival. METHODS: Transient systemic hypoxia-ischemia (TSHI) on embryonic Day 18
      in rats mimics human early-third trimester placental insufficiency. This model
      was used to test the authors' hypothesis using a novel clinically relevant
      paradigm of prenatal injury on embryonic Day 18, neonatal systemic rhEPO
      administration initiated 4 days after injury on postnatal Day 1, and
      histological, biochemical, and functional analyses in neonatal, juvenile, and
      adult rats. RESULTS: The results showed that prenatal TSHI upregulates brain EPO
      receptors, but not EPO ligand. Sustained EPO receptor upregulation was pronounced
      on oligodendroglial lineage cells and neurons, neural cell populations
      particularly prone to loss from CNS injury due to preterm birth. Postnatal rhEPO
      administration after prenatal TSHI minimized histological damage and rescued
      oligodendrocytes and gamma-aminobutyric acidergic interneurons. Myelin basic
      protein expression in adult rats after insult was reduced compared with sham
      controls, but could be restored to near normal levels by neonatal rhEPO
      treatment. Erythropoietin-treated TSHI rats performed significantly better than
      their saline-treated peers as adults in motor skills tests, and showed
      significant seizure threshold restoration using a pentylenetetrazole increasing
      dose paradigm. CONCLUSIONS: These data demonstrate that neonatal rhEPO
      administration in a novel clinically relevant paradigm initiated 4 days after a
      global prenatal hypoxic-ischemic insult in rats rescues neural cells, and induces
      lasting histological and functional improvement in adult rats.

PMID- 20809705
TI  - Neurosurgical treatment of progressive posthemorrhagic ventricular dilation in
      preterm infants: a 10-year single-institution study.
AB  - OBJECT: Intraventricular hemorrhage (IVH) and progressive posthemorrhagic
      ventricular dilation (PPHVD) may result in significant neurological morbidity in
      preterm infants. At present, there is no consensus regarding the optimal timing
      or type of neurosurgical procedure to best treat PPHVD. Conflicting data exist
      regarding the relative risks and benefits of two commonly used temporizing
      neurosurgical procedures (TNPs), ventricular access devices ([VADs] or
      ventricular reservoirs) versus ventriculosubgaleal (VSG) shunts. This study was
      designed to address this issue. METHODS: This is a single-center, 10-year
      retrospective review of all preterm infants admitted to the St. Louis Children's
      Hospital neonatal intensive care unit (NICU) with Papile Grade III-IV IVH. The
      development of PPHVD and the requirement for and type of TNP were recorded. Rates
      of TNP complication, ventriculoperitoneal (VP) shunt implantation, shunt
      infection, and mortality rates were used to compare the efficacy and limitations
      of each TNP type. RESULTS: Over this 10-year interval, 325 preterm infants with
      Grade III-IV IVH were identified, with trends showing an increasing number of
      affected infants annually, and an increasing number of TNPs were required
      annually. Ninety-five (29.2%) of the 325 infants underwent a TNP for PPHVD (65
      VADs, 30 VSG shunts). The rate of permanent VP shunt implantation for all TNPs
      was 72.6% (69 of 95 infants). Forty-nine (75.4%) of the 65 infants treated with
      VADs and 20 (66.7%) of the 30 treated with VSG shunts required VP shunts (p =
      0.38). There was no statistical difference between VAD or VSG shunt with regard
      to TNP-related infection (p = 0.57), need for TNP revision (p = 0.16), subsequent
      shunt infection (p = 0.77), shunt revision rate (p = 0.58), or mortality rate (p
      = 0.24). CONCLUSIONS: Rates of IVH and PPHVD observed at the authors' center have
      increased over time. In contrast to recent literature, the results from the
      current study did not demonstrate a difference in complication rate or
      requirement for permanent VP shunt placement between VADs and VSG shunts.
      Definitive conclusions will require a larger, prospective trial.

PMID- 20809706
TI  - Vertebrobasilar dissections.

PMID- 20809707
TI  - Symptomatic spontaneous vertebrobasilar dissections in children: review of 29
      consecutive cases.
AB  - OBJECT: The purpose of this study is to analyze the clinical presentation,
      morphological characteristics, angio-architecture, and outcome of vertebrobasilar
      dissection (VBD) in the pediatric population. METHODS: The authors
      retrospectively reviewed 29 consecutive cases involving children younger than 16
      years of age who were diagnosed with symptomatic VBDs. Data were gathered with
      respect to the patient's age, sex, clinical history, associated underlying
      disease, and symptoms (headache, vertigo) as well as the location of the
      dissection and the imaging appearance. RESULTS: The patients' mean age was 8.24
      years (range 2 months-15 years). There was an overall 3:1 male predominance,
      although among children older than 8 years, girls and boys were similarly
      affected. Hemorrhagic dissections occurred in 10 of 29 cases. In nonhemorrhagic
      dissections, stroke occurred in 16 cases, with the most common presenting
      symptoms being headaches and vertigo; in the other 3 cases, mass effect due to a
      chronic dissecting aneurysm was present. In 7 children an underlying vessel wall
      disease was found. The location of the dissection was extradural in 11 cases and
      intradural in the remainder. There was no preference with respect to side. The
      basilar artery was affected in 9 patients. CONCLUSIONS: The imaging appearance
      and clinical presentation of symptomatic VBDs in the pediatric population differs
      from that in adults. Boys are more often affected, especially at younger ages,
      and hemorrhagic presentation is more common, presumably owing to the fact that
      the basilar artery is more commonly involved. Depending on the pathogenetic
      mechanism underlying the dissection, different clinical symptoms will evolve,
      necessitating individually tailored treatment.

PMID- 20809708
TI  - Diffuse and uncontrolled vascular smooth muscle cell proliferation in rapidly
      progressing pediatric moyamoya disease.
AB  - Moyamoya disease is a rare stroke syndrome of unknown etiology resulting from
      stenosis or occlusion of the supraclinoid internal carotid artery (ICA) in
      association with an abnormal vascular network in the basal ganglia. Although the
      highest incidence of moyamoya disease is in pediatric patients, pathology reports
      have been primarily limited to adult samples and describe occlusive fibrocellular
      lesions in the intimae of affected arteries. We describe the case of a young girl
      with primary moyamoya disease who presented at 18 months of age with right
      hemiparesis following an ischemic stroke. Angiography showed stenosis of the
      distal left ICA, left middle cerebral artery, and right ICA. An emergent left
      sided dural inversion was performed. Recurrent strokes and alternating hemiplegia
      necessitated a right dural inversion 6 months later. Nonetheless, her aggressive
      disease proved uniquely refractory to surgical revascularization, and she
      succumbed to recurrent strokes and neurological deterioration at 2.5 years of
      age. Pathological specimens revealed a striking bilateral occlusion of the
      anterior carotid circulation resulting from intimal proliferation of smooth
      muscle cells (SMCs). Most strikingly, the ascending aorta and the superior
      mesenteric artery demonstrated similar intimal proliferation, along with SMC
      proliferation in the media. The systemic pathology involving multiple arteries in
      this extremely young child, the first case of its kind available for autopsy,
      suggests that globally uncontrolled SMC proliferation, in the absence of
      environmental risk factors and likely resulting from an underlying genetic
      alteration, may be a primary etiologic event leading to moyamoya disease.

PMID- 20809709
TI  - Care of pediatric neurosurgical patients in Iraq in 2007: clinical and ethical
      experience of a field hospital.
AB  - OBJECT: Care for host-nation pediatric casualties and disease or nonbattle
      injuries is an essential mission of deployed military medical assets. Clinical
      experience with pediatric patients at field hospitals has been increasingly
      reported since 2001, with neurotrauma identified as a major cause of morbidity
      and death in this population. A concentrated pediatric neurosurgical experience
      at a deployed medical facility has not been reported. The authors reviewed their
      experience with pediatric neurosurgical patients at a field hospital in Iraq in
      2007 to provide insight into the management of this patient population. METHODS:
      A retrospective review was conducted using a prospective database constructed by
      the authors for quality improvement during a single combat rotation in 2007.
      RESULTS: Forty-two patients among 287 consultations were 17 years of age or
      younger. Twenty-six of these children were 8 years old or younger. Penetrating
      head injuries were the most common indication for consultation (22 of 42
      patients). Twenty-eight of 130 surgical procedures were performed in the
      children. One patient died in the perioperative period, for a trauma-related
      operative mortality rate of 4%. Seven patients received palliative care based on
      the extent of presenting injuries. Twenty-five patients were discharged with
      minimal or no neurological deficits. CONCLUSIONS: Pediatric patients represent a
      significant proportion of the neurosurgical patient volume at field medical
      hospitals in the Iraqi theater. The mature medical theater environment present in
      2007 allowed for remarkable diagnostic evaluation and treatment of these
      patients. Penetrating and closed craniospinal injuries were the most common
      indication for consultation. Disease and nonbattle injuries were also
      encountered, with care provided when deemed appropriate. The deployed environment
      presents unique medical and ethical challenges to neurosurgeons serving in
      forward medical facilities.

PMID- 20809710
TI  - Complete versus anterior two-thirds corpus callosotomy in children: analysis of
      outcome.
AB  - OBJECT: The goal of this study was to evaluate the efficacy of anterior versus
      complete sectioning of the corpus callosum in children suffering from medically
      refractory epilepsy. The authors report seizure outcome in patients who underwent
      anterior two-thirds or complete corpus callosotomy (CC) during the period 1995
      2008 at St. Louis Children's Hospital. METHODS: The medical records of 27
      children and adolescents with a minimum follow-up of 6 months were
      retrospectively evaluated with respect to seizure status, anticonvulsant
      outcomes, and subjective results. Preoperatively, patients suffered from a
      variety of seizure types that occurred daily, weekly, or episodically. The
      male/female ratio was 19:8, and patients ranged in age between 3 and 19 years
      (mean 9.93 years). Seizure outcome, parental assessment of daily function, and
      changes in the number of prescribed antiepileptic drugs were all assessed.
      RESULTS: Fifteen patients underwent an initial anterior two-thirds CC, and 12
      underwent a complete CC. Of the 15 patients who underwent an anterior CC, 7 went
      on to receive a posterior CC. Seizure control was superior in children undergoing
      a complete CC (91%, Class I-III) versus an anterior two-thirds CC (75%, Class I
      III). Seizure types most affected by CC included atonic, myoclonic, and absence.
      The number of postoperative antiepileptic drugs did not significantly change
      following CC in either the anterior only or complete groups. One patient
      experienced a transient disconnection syndrome that resolved within 4 weeks, and
      4 patients experienced mild hemiparesis and speech delays that resolved with
      therapy. Three patients experienced surgical complications requiring a second
      operation. The overall daily function and attentiveness of the patients improved.
      CONCLUSIONS: A complete CC should be considered as the initial procedure in lower
      functioning children afflicted by absence, atonic, or myoclonic seizures.
      Severely affected higher-functioning children may also benefit from a complete
      CC, without clinically significant disconnection syndromes. A completion
      posterior CC may benefit patients in whom a prior anterior CC has failed.

PMID- 20809711
TI  - Surgically treated movement disorders associated with heterotopia: report of 2
      cases.
AB  - Heterotopic gray matter has been implicated in epilepsy; however, not much is
      known regarding heterotopia beyond epilepsy. Here, the authors describe 2
      pediatric patients with deep heterotopias contiguous with basal ganglia
      structures. These heterotopias appear to have manifested as movement disorders.
      One patient presented with a left-sided myoclonus and choreiform movements
      associated with a right caudate heterotopia; she experienced vast improvement
      after resection of periventricular heterotopia. The other patient presented with
      progressive dystonia and a ballistic movement disorder. Initial bilateral globus
      pallidus internus stimulation resulted in successful treatment of the dystonia;
      however, her movement disorder worsened. After an extensive workup, including
      STATISCOM (statistical ictal SPECT coregistered to MR imaging), the patient
      underwent cortical stimulation with improvement in her movement disorder. To the
      best of our knowledge, these cases are the first reported instances of
      heterotopic gray matter associated with movement disorders. Both patients
      experienced significant improvements following resection of their heterotopias.

PMID- 20809712
TI  - Efficacy of intraoperative irrigation with saline for preventing shunt infection.
AB  - OBJECT: The rate of infection following shunt procedures is unacceptably high.
      The authors have hypothesized that the key to reducing the shunt infection rate
      is in reducing bacteria in the operating field and wound. This hypothesis has
      been tested in a prospective nonrandomized controlled manner. METHODS: Data
      obtained in all patients undergoing shunt insertions or revisions for
      hydrocephalus performed between October 1, 2003, and June 12, 2009, were
      reviewed. Starting in August 2006, we began routinely irrigating the operating
      field and wound with saline solution from a syringe. Prior to this, we had not
      used any irrigation techniques, providing an adequate control group (Group A) for
      the effect of the irrigation technique. Prior to November 2007, we used saline
      containing amikacin for irrigation (Group B). After that date, we used saline
      only for irrigation (Group C). RESULTS: A total of 150 shunt procedures were
      performed in 79 girls and 71 boys during the study period. The mean age of all
      patients was 44.0 +/- 59.1 months. Groups A, B, and C comprised 61, 40, and 49
      shunt procedures, respectively. There was no statistical difference in age among
      the 3 groups. Nine infections occurred within 90 days in the postoperative
      period. The overall infection rate was 6.0%. Eight infections occurred before
      introducing the irrigation procedure (infection rate 13.1%). One infection was
      noted after introducing irrigation (Group B [0.0%] + Group C [2.0%]; combined B
      and C infection rate = 1.1%). There was a statistical difference in the infection
      rate between Group A and Groups B and C combined (p = 0.003), Groups A and B (p =
      0.021), and Groups A and C (p = 0.035). In contrast, no statistical difference
      was observed between Groups B and C (p > 0.99). Six of the 9 infections were due
      to staphylococcal species. CONCLUSIONS: An irrigation technique used to reduce
      bacteria in the operating field and wound is effective for preventing shunt
      infection. Irrigation alone, and not antibiotics, contributed to the prophylaxis
      of shunt infection.

PMID- 20809713
TI  - Reinfection following initial cerebrospinal fluid shunt infection.
AB  - OBJECT: Significant variation exists in the surgical and medical management of
      CSF shunt infection. The objectives of this study were to determine CSF shunt
      reinfection rates following initial CSF shunt infection in a large patient cohort
      and to determine management, patient, hospital, and surgeon factors associated
      with CSF shunt reinfection. METHODS: This retrospective cohort study included
      children who were in the Pediatric Health Information System (PHIS) database, who
      ranged in age from 0 to 18 years, and who underwent uncomplicated initial CSF
      shunt placement in addition to treatment for initial CSF shunt infection between
      January 1, 2001, and December 31, 2008. The outcome was CSF shunt reinfection
      within 6 months. The main predictor variable of interest was surgical approach to
      treatment of first infection, which was determined for 483 patients. Covariates
      included patient, hospital, surgeon, and other management factors. RESULTS: The
      PHIS database includes 675 children with initial CSF shunt infection. Surgical
      approach to treatment of the initial CSF shunt infection was determined for 483
      children (71.6%). The surgical approach was primarily shunt removal/new shunt
      placement (in 286 children [59.2%]), but a substantial number underwent
      externalization (59 children [12.2%]), of whom a subset went on to have the
      externalized shunt removed and a new shunt placed (17 children [3.5% overall]).
      Other approaches included nonsurgical management (64 children [13.3%]) and
      complete shunt removal without shunt replacement (74 children [15.3%]). The 6
      month reinfection rate was 14.8% (100 of 675 patients). The median time from
      infection to reinfection was 21 days (interquartile range [IQR] 5-58 days).
      Children with reinfection had less time between shunt placement and initial
      infection (median 50 vs 79 days, p = 0.06). No differences between those with and
      without reinfection were seen in patient factors (patient age at either shunt
      placement or initial infection, sex, race/ethnicity, payer, indication for shunt,
      number of comorbidities, distal shunt location, and number of shunt revisions at
      first infection); hospital volume; surgeon volume; or other management factors
      (for example, duration of intravenous antibiotic use). Nonsurgical management was
      associated with reinfection, and complete shunt removal was negatively associated
      with reinfection. However, reinfection rates did not differ between the 2 most
      common surgical approaches: shunt removal/new shunt placement (44 [15.4%] of 286;
      95% CI 11.4%-20.1%) and externalization (total 12 [20.3%] of 59; 95% CI 11.0%
      32.8%). Externalization followed by shunt removal/new shunt placement (5 [29.4%]
      of 17; 95% CI 10.3%-56.0%) and nonsurgical management (15 [23.4%] of 64; 95% CI
      13.8%-35.7%) had higher, but nonstatistically significant, reinfection rates. The
      length of stay was shorter for nonsurgical management. CONCLUSIONS: Surgical
      approach to treatment of initial CSF shunt infection was not associated with
      reinfection in this large cohort of patients.

PMID- 20809714
TI  - Low-grade myofibroblastic sarcoma of the sacrum.
AB  - Myofibroblastic tumors are soft-tissue neoplasms arising from myofibroblasts,
      ubiquitous cells sharing ultrastructural features of muscular and fibroblastic
      cells. Vasudev and Harris described a malignant counterpart of these benign
      tumors in 1978. Most reported cases of myofibroblastic sarcoma have arisen in the
      head and neck region and the soft tissues of the extremities. To the best of the
      authors' knowledge, there have been only 8 previous reports on primary
      myofibroblastic sarcoma of the bone. The authors report a new case of this rare
      tumor affecting the sacrum and ilium of a 15-year-old girl and discuss the role
      of total sacrectomy and lumbopelvic reconstruction for treatment of this disease.

PMID- 20809715
TI  - Gliomatosis cerebri: report of 3 cases.
AB  - Gliomatosis cerebri is an uncommon glial neoplasm that is exceedingly rare in
      children and difficult to diagnose. The authors describe the presentation and
      diagnosis of GC in 3 children ages 12, 14, and 16 years. These children exhibited
      signs and symptoms of increased intracranial pressure as well as other vague or
      site specific neurological signs. Because clinical presentation, CSF analysis,
      and neuroimaging were nonspecific, a stereotactic biopsy to obtain tissue for
      pathological review was ultimately necessary to confirm the diagnosis. These
      pediatric cases underscore the limitations of relying solely on clinical
      presentation and neuroimaging and call to attention the essential role of
      neurosurgical intervention. The authors emphasize the need to maintain
      gliomatosis cerebri in the differential diagnosis of children presenting with
      diffuse neurological signs and MR imaging evidence of widespread, infiltrative
      lesions.

PMID- 20809716
TI  - Germinoma with malignant transformation to nongerminomatous germ cell tumor.
AB  - The authors describe the case of a young girl with suprasellar germinoma. Six
      weeks after this diagnosis, just prior to initiation of therapy, serum and CSF
      marker analysis revealed sudden and marked elevation of alpha-fetoprotein,
      indicating transformation of her germinoma to a nongerminomatous germ cell tumor.
      She underwent chemotherapy and radiation therapy per the national treatment
      approach for the new diagnosis, with subsequent return of her serum and CSF tumor
      markers to normal levels. To the authors' knowledge, this is the first case in
      the English-language literature of a nongerminomatous germ cell tumor resulting
      from conversion of germinoma at the original site of presentation.

PMID- 20809717
TI  - Radiographic assessment of snap-shunt failure: report of 2 cases.
AB  - Accurate assessment of imaging studies in patients with ventriculoperitoneal
      shunts can be aided by empirical findings. The authors characterize an objective
      measurement easily performed on head CT scans with the goal of producing clear
      evidence of shunt fracture or disconnection in patients with a snap shunt-type
      system. The authors describe 2 cases of ventriculoperitoneal shunt failure
      involving a fracture and a disconnection associated with a snap-shunt assembly.
      In both cases the initial clinical symptoms were not convincing for shunt
      malfunction, and the interpretation of the CT finding failed to immediately
      identify the abnormality. As the clinical picture became more convincing for
      shunt malfunction, each patient subsequently underwent successful shunt revision.
      The authors reviewed the CT scans of 10 patients with an intact and functioning
      snap-shunt system to characterize the normal appearance of the snap-shunt
      connection. On CT scans the distance between the radiopaque portion of the
      ventricular catheter and the radiopaque portion of the reservoir dome measures an
      average of 4.72 mm (range 4.6-4.9 mm, 95% CI 4.63-4.81 mm). In the authors'
      patient with a fractured ventricular catheter, this interval measured 7.8 mm, and
      in the patient with a disconnection it measured 7.7 mm. In comparison with the
      range of normal values, a radiolucent interval significantly greater than 4.9 mm
      should promptly raise concern for a disconnected or fractured shunt in this
      system. This measurement may prove particularly useful when serial imaging is not
      readily available.

PMID- 20809718
TI  - Cerebellar mutism.

PMID- 20809719
TI  - Microvessel density.

PMID- 20809720
TI  - Motion preservation following anteriorcervical discectomy.

PMID- 20809721
TI  - Radiological changes of the operated and adjacent segments following cervical
      arthroplasty after a minimum 24-month follow-up: comparison between the Bryan and
      Prodisc-C devices.
AB  - OBJECT: The purposes of this retrospective study were to determine the
      radiological changes at the index and adjacent levels after cervical arthroplasty
      using the Bryan disc and Prodisc-C disc after a minimum 24 months follow-up, and
      to demonstrate the possible clinical factors related to these changes. METHODS:
      Following single-level cervical arthroplasty using either the Bryan disc or
      Prodisc-C, the degree of facet degeneration and other radiological changes at the
      index and adjacent levels were assessed by observing radiographs and CT scans at
      a minimum 24 months after the operations. These findings were determined in
      relation to the clinical outcome, various perioperative factors, and prosthesis
      factors. Thirty-six patients were included in this investigation (19 in the Bryan
      disc group and 17 in the Prodisc-C group). RESULTS: At the index level,
      progression of facet arthrosis (PFA) was observed in 7 of 36 levels (1 level with
      the Bryan disc, 6 with the Prodisc-C). At adjacent levels, PFA was minimally
      observed. Heterotopic ossification (HO) was observed at 19 levels (11 with the
      Bryan disc, 8 with Prodisc-C). Progression of facet arthrosis at the index
      segments was positively related to malposition of the prosthesis on the frontal
      plane, and decreased postoperative functional spinal unit range of motion at the
      index level. Occurrence of HO was correlated with the preoperative calcification
      of the posterior longitudinal ligament at the operated level, regardless of
      prosthesis type. Clinical outcome and the occurrence of PFA or HO did not show
      any significant relationship. CONCLUSIONS: This study demonstrates that the
      incidence of PFA at the index level is 19.4% after a minimum 24-month follow-up,
      and occurs more frequently in the Prodisc-C group. Progression of facet arthrosis
      is related to less functional spinal unit range of motion and anterior placement
      of the prosthesis. The occurrence rate of HO is high, regardless of the type of
      prosthesis, and it is significantly correlated with preoperative calcification of
      the posterior longitudinal ligament at the operated level.

PMID- 20809722
TI  - Long-term clinical and radiographic outcomes of cervical disc replacement with
      the Prestige disc: results from a prospective randomized controlled clinical
      trial.
AB  - OBJECT: The purpose of this study was to determine long-term clinical outcomes in
      patients undergoing anterior cervical surgery in which a cervical disc prosthesis
      was used to treat single-level degenerative cervical disc disease. METHODS: In
      this prospective, nonblinded study, 541 patients at 32 investigational sites were
      randomly assigned to 1 of 2 treatment groups. The results of the investigational
      group, in which patients received the Prestige disc prosthesis, were compared
      with those of the control group, in which patients underwent an instrumented
      interbody fusion. Data were collected preoperatively, intraoperatively, and at
      1.5, 3, 6, 12, 24, 36, and 60 months postoperatively. To date, 271 patients have
      completed 5 years of clinical follow-up (144 investigational and 127 control
      patients). RESULTS: Significant improvements in Neck Disability Index (NDI)
      scores, Physical Component Summary scores of the 36-Item Short-Form Health
      Survey, and neck and arm pain scores were achieved by 1.5 months in both groups
      and sustained at 5 years. The mean NDI improvements from preoperative scores were
      35.4, 36.3, and 38.4 at 24, 36, and 60 months, respectively, in the
      investigational group. The corresponding mean NDI improvements were 33.9, 31.3,
      and 34.1 in the control group. The intergroup differences at both 36 and 60
      months were significant (p = 0.008 and 0.022, respectively). The overall rates of
      maintenance or improvement in neurological status in the investigational group
      were 91.6%, 92.8%, and 95.0%, respectively, at 24, 36, and 60 months compared
      with 83.6%, 83.2%, and 88.9% in the control group (p = 0.006, 0.004, and 0.051,
      respectively). The implant effectively maintained angular motion, averaging more
      than 7.3 degrees at 36 months and 6.5 degrees at 60 months after surgery. No
      implant migration was observed up to 60 months. There were statistically
      significant differences between the investigational and control groups with
      regard to the rate of revision and supplemental fixation surgical procedures
      performed subsequent to the index procedure. Additional surgical procedures for
      adjacent-segment disease were observed in both treatment groups. Rates for
      surgery at adjacent levels trended lower in the investigational group (8 patients
      [11 surgeries]) compared with those in the control group (13 patients [16
      surgeries]), but the differences were not statistically significant (p = 0.376).
      Some of the second surgeries involved both index and adjacent levels.
      CONCLUSIONS: The Prestige disc maintains improved clinical outcomes and segmental
      motion after implantation at 5-year follow-up.

PMID- 20809723
TI  - Using the T2-weighted magnetic resonance imaging signal intensity ratio and
      clinical manifestations to assess the prognosis of patients with cervical
      ossification of the posterior longitudinal ligament.
AB  - OBJECT: The aim of this study was to investigate the clinical significance of
      both the signal intensity ratio obtained from MR imaging and clinical
      manifestations on the prognosis of patients with cervical ossification of the
      posterior longitudinal ligament. METHODS: The authors retrospectively reviewed
      the records of 58 patients with cervical ossification of the posterior
      longitudinal ligament who underwent cervical laminoplasty from February 1999 to
      July 2007. Magnetic resonance imaging (1.5-T) was performed in all patients
      before surgery. Sagittal T2-weighted images of the cervical spinal cord
      compressed by the ossified posterior longitudinal ligament showed increased
      intramedullary signal intensity, whereas the sagittal images obtained at the C7
      T1 disc levels were of normal intensity. The signal intensity ratio between
      regions of intramedullary increased signal intensity and the normal C7-T1 disc
      level was calculated based on the signal intensity values generated from the MR
      imaging workstation. Patients were divided into 3 groups according to their
      signal intensity ratio (high, intermediate, and low signal intensity groups).
      RESULTS: There were significant differences between the 3 groups regarding
      recovery rate (p < 0.001), age (p = 0.022), duration of disease (p = 0.001),
      Babinski sign (p < 0.001), ankle clonus (p < 0.001), and both pre- and
      postoperative Japanese Orthopaedic Association score (p < 0.001). There was no
      significant difference in sex among the 3 groups (p = 0.391). CONCLUSIONS:
      Patients with low signal intensity ratios that changed on T2-weighted imaging
      experienced a good surgical outcome. Low increased signal intensity might reflect
      mild neuropathological alteration in the spinal cord and greater recuperative
      potential. An increased signal intensity ratio with positive pyramidal signs
      indicates less recuperative potential of the spinal cord and a poor surgical
      outcome.

PMID- 20809724
TI  - Reliability analysis of the epidural spinal cord compression scale.
AB  - OBJECTIVE: The evolution of imaging techniques, along with highly effective
      radiation options has changed the way metastatic epidural tumors are treated.
      While high-grade epidural spinal cord compression (ESCC) frequently serves as an
      indication for surgical decompression, no consensus exists in the literature
      about the precise definition of this term. The advancement of the treatment
      paradigms in patients with metastatic tumors for the spine requires a clear
      grading scheme of ESCC. The degree of ESCC often serves as a major determinant in
      the decision to operate or irradiate. The purpose of this study was to determine
      the reliability and validity of a 6-point, MR imaging-based grading system for
      ESCC. METHODS: To determine the reliability of the grading scale, a survey was
      distributed to 7 spine surgeons who participate in the Spine Oncology Study
      Group. The MR images of 25 cervical or thoracic spinal tumors were distributed
      consisting of 1 sagittal image and 3 axial images at the identical level
      including T1-weighted, T2-weighted, and Gd-enhanced T1-weighted images. The
      survey was administered 3 times at 2-week intervals. The inter- and intrarater
      reliability was assessed. RESULTS: The inter- and intrarater reliability ranged
      from good to excellent when surgeons were asked to rate the degree of spinal cord
      compression using T2-weighted axial images. The T2-weighted images were superior
      indicators of ESCC compared with T1-weighted images with and without Gd.
      CONCLUSIONS: The ESCC scale provides a valid and reliable instrument that may be
      used to describe the degree of ESCC based on T2-weighted MR images. This scale
      accounts for recent advances in the treatment of spinal metastases and may be
      used to provide an ESCC classification scheme for multicenter clinical trial and
      outcome studies.

PMID- 20809725
TI  - Predictors of long-term outcome in an elderly group after laminectomy for lumbar
      stenosis.
AB  - OBJECT: This is a retrospective long-term outcome study of results after
      laminectomy for lumbar spinal stenosis in an elderly group of patients. The study
      was designed to evaluate possible demographic, comorbidity, and clinical
      prognosticators for pain reduction and functional improvement in this population.
      Because the assessment of functional outcome in the elderly is complicated by
      several specific factors, the use of outcome measurement parameters should be
      revised and refined. Moreover, despite numerous relevant studies, the results of
      various techniques remain equivocal, particularly among the elderly, which
      renders the implementation of focused studies necessary. New data could be used
      to refine patient selection and choice of technique to improve prognosis.
      METHODS: During a 5-year period, lumbar laminectomies were performed in 182
      elderly patients. Of these 182, 125 patients (68.8%) were followed up for a mean
      period of 60.8 months. The outcome was assessed by means of pain visual analog
      scale (VAS) pain score, Oswestry Disability Index (ODI), and patient satisfaction
      questionnaire, and results were correlated to demographic (age, sex), comorbidity
      (Charlson Comorbidity Index, diabetes, depression, and history of lumbar spine
      surgery), and clinical (main preoperative complaint, preoperative VAS score, and
      ODI) factors. RESULTS: In terms of the VAS score, 106 patients (84.8%) exhibited
      improvement at follow-up. The corresponding ODI improvement rate was 69.6% (87
      patients). The mean VAS and ODI differences were 5.1 and 29.1, respectively. One
      hundred two patients (81.6%) were satisfied with the results of the operation.
      Univariate analysis for possible prognostic factors revealed the significant
      influence of low-back pain on VAS score (p = 0.024) and ODI (p < 0.001) not
      improving, while the ODI was also affected by sex (females had a poorer outcome
      [p = 0.019]). In contrast, patient satisfaction was not related to any of the
      preoperative parameters recorded; nevertheless, it was strongly related to all
      functional measurements on follow-up. CONCLUSIONS: Considering the methodological
      issues of such studies, particularly in elderly patients, the authors conclude
      that the ODI is more sensitive than the VAS score in assessing prognostic value
      and that patient satisfaction is difficult to prognosticate, underscoring the
      particularities that this population presents regarding functionality assessment.
      Considering the prognostic value of preoperative factors, a negative influence of
      low-back pain and female sex is reported.

PMID- 20809726
TI  - Progression of low back and lower extremity pain in a cohort of patients with
      achondroplasia.
AB  - OBJECT: The aim of this study was to assess the natural history of pain
      associated with spinal stenosis in individuals with achondroplasia and to
      characterize pain patterns and associated functional and psychological effects.
      METHODS: The authors measured pain severity, spatial distribution of pain,
      functional disability, psychological distress, physical symptoms other than pain,
      and healthcare utilization in 181 individuals with achondroplasia. They also
      assessed low back and/or lower extremity pain at the initial visit and 1-year
      follow-up via self-rated patient questionnaires, calculated composite scores from
      responses via component analyses, and used repeated measures linear regression
      analyses for score changes (significance, p < or = 0.05). RESULTS: At the follow
      up, back pain severity was unchanged. Patients reported significant progression
      of pain toward involvement of the lower extremities and significant increases in
      lower extremity pain severity overall. There were also significant increases in
      healthcare utilization overall. Compared with patients with back pain only, those
      with back pain and proximal or distal leg pain had higher self-rated pain
      severity; higher functional disability; and more bowel and bladder dysfunction
      symptoms, sleep disturbances, extremity numbness, and psychological distress.
      CONCLUSIONS: Individuals with achondroplasia and symptomatic spinal stenosis
      often experience back pain, which may progress to lower extremity pain and
      debilitating consequences. A more thorough understanding of the progression of
      spatial pain characteristics and pain severity may aid clinical decision making
      regarding the optimal timing for intervention.

PMID- 20809727
TI  - Laser-guided lumbar medial branch kryorhizotomy.
AB  - The authors describe a modification of the medial branch kryorhizotomy technique
      for the treatment of lumbar facet joint syndrome using a fluoroscopy-based laser
      guided method. A total of 32 patients suffering from lumbar facet joint syndrome
      confirmed by positive medial nerve block underwent conventional or laser-guided
      kryorhizotomy. The procedural time (20.6 +/- 1.0 vs 16.3 +/- 0.9 minutes, p <
      0.01), fluoroscopy time (54.1 +/- 3.5 vs 28.2 +/- 2.4 seconds, p < 0.01),
      radiation dose (407.5 +/- 32.0 vs 224.1 +/- 20.3 cGy/cm(2), p < 0.01), and
      patient discomfort during the procedure (7.1 +/- 0.4 vs 5.2 +/- 0.4 on the visual
      analog scale, p < 0.01) were significantly reduced in the laser-guided group.
      There was a tendency for a better positioning accuracy when the laser guidance
      method was used (3.0 +/- 0.3 vs 2.2 +/- 0.3 mm of deviation from the target
      points, p > 0.05). No difference in the outcome was observed between the 2 groups
      of patients (visual analog scale score 3.5 +/- 0.2 vs 3.3 +/- 0.3, p > 0.05).
      This improved minimally invasive surgical technique offers advantages to
      conventional fluoroscopy-based kryorhizotomy.

PMID- 20809728
TI  - A novel approach to the upper anterior thoracic spine: a cadaveric feasibility
      study.
AB  - OBJECT: Surgical approaches to the upper anterior thoracic spine can be a
      challenge. Various techniques such as transsternal routes have been employed but
      access to the midthoracic vertebrae is limited due to the position of the heart
      and great vessels. In the present study the authors' goal was to evaluate in
      cadavers a novel approach to the upper anterior thoracic spine. METHODS: In 12
      adult cadavers the majority of the left first rib was removed following
      infraclavicular transection of the attachment of the anterior and middle scalene
      muscles from this bone. Inferior retraction of the parietal pleura and lung was
      performed and dissection was carried out inferior to the left subclavian artery
      and superior and posterior to the aorta, to the anterior aspect of the upper
      thoracic spine. RESULTS: The aforementioned approach and surgical corridor
      allowed a good access to the anterior aspect of the upper thoracic vertebrae and
      caudally to the inferior aspect of T-4 vertebral body in all cadavers. No obvious
      neurovascular injury was identified in any specimen. CONCLUSIONS: To the authors'
      knowledge, the method described herein has not been previously reported. Based on
      their cadaveric study, they believe such an approach can be used in the patients
      with pathology in this region of the thoracic spine. Surgical series are now
      needed to confirm our findings.

PMID- 20809729
TI  - Thoracic and lumbar intraforaminal ligaments.
AB  - OBJECT: The author conducted a study to investigate the anatomy of the
      intraforaminal ligaments of the thoracic and lumbar nerve roots and describe
      their anatomical relationships and functional properties. This anatomical study
      performed on the intervertebral foramina, intraforaminal ligaments,
      transforaminal ligaments, and nerve roots of the thoracic and lumbar spine was
      performed in human cadavers. METHODS: The foraminal anatomy was studied in 11
      whole cadavers (5 females, 6 males) previously prepared with formaldehyde, whose
      ages at the time of death ranged from 16 to 71 years. The thoracic and lumbar
      spinal columns were separated from the cervical and sacral segments en bloc using
      an electric band saw. The paraspinal muscles and their attachments were removed
      by sharp and meticulous dissection, and the thoracic and lumbar intervertebral
      foramina were examined under a surgical microscope. The intervertebral foraminal
      ligaments and nerve roots were exposed. The foraminal contents were identified
      and studied in detail. The intraforaminal ligaments were stained using H & E to
      determine ligamentous fiber. RESULTS: Intraforaminal ligaments connect the
      periosteum and transforaminal ligaments to the nerve root sleeves and vessels
      within the fatty areolar tissue. Histologically, the ligamentous attachment of
      the nerve roots within the foramina consists of adipose and connective tissue.
      CONCLUSIONS: The nerve roots are surrounded by intraforaminal ligaments, which
      may act in conjunction with the dura and periosteum to protect the nerve roots
      mechanically.

PMID- 20809730
TI  - Anatomy and landmarks for the superior and middle cluneal nerves: application to
      posterior iliac crest harvest and entrapment syndromes.
AB  - OBJECT: To date, only scant descriptions of the cluneal nerves are available. As
      these nerves, and especially the superior group, may be encountered and injured
      during posterior iliac crest harvest for spinal arthrodesis procedures, the
      present study was performed to better elucidate their anatomy and to provide
      anatomical landmarks for their localization. METHODS: The superior and middle
      cluneal nerves were dissected from their origin to termination in 20 cadaveric
      sides. The distance between the posterior superior iliac spine (PSIS) and
      superior cluneal nerves at the iliac crest and the distance between this bony
      prominence and the origin of the middle cluneals were measured. The specific
      course of each nerve was documented, and the diameter and length of all cluneal
      nerves were measured. RESULTS: Superior and middle cluneal nerves were found on
      all sides. An intermediate superior cluneal nerve and lateral superior cluneal
      nerve were not identified on 4 and 5 sides, respectively. The superior cluneal
      nerves always passed through the psoas major and paraspinal muscles and traveled
      posterior to the quadratus lumborum. The mean diameters of the superior and
      middle cluneal nerves were 1.1 and 0.8 mm, respectively. From the PSIS, the
      superior cluneal branches passed at means of 5, 6.5, and 7.3 cm laterally on the
      iliac crest. At their origin, the middle cluneal nerves had mean distances of 2
      cm superior to the PSIS, 0 cm from the PSIS, and 1.5 cm inferior to the PSIS. In
      their course, the middle cluneal nerves traversed the paraspinal muscles
      attaching onto the dorsal sacrum. CONCLUSIONS: Knowledge of the cutaneous nerves
      that cross the posterior aspect of the iliac crest may assist in avoiding their
      injury during bone harvest. Additionally, an understanding of the anatomical
      pathway that these nerves take may be useful in decompressive procedures for
      entrapment syndromes involving the cluneal nerves.

PMID- 20809731
TI  - Early complications in spine surgery and relation to preoperative diagnosis: a
      single-center prospective study.
AB  - OBJECT: The reported incidence of complications in spine surgery varies widely.
      Variable study methodologies may open differing avenues for potential bias, and
      unclear definitions of perioperative complication make analysis of the literature
      challenging. Although numerous studies have examined the morbidity associated
      with specific procedures or diagnoses, no prospective analysis has evaluated the
      impact of preoperative diagnosis on overall early morbidity in spine surgery. To
      accurately assess perioperative morbidity in patients undergoing spine surgery, a
      prospective analysis of all patients who underwent spine surgery by the
      neurosurgical service at a large tertiary care center over a 6-month period was
      conducted. The correlation between preoperative diagnosis and the incidence of
      postoperative complications was assessed. METHODS: Data were prospectively
      collected on 248 consecutive patients undergoing spine surgery performed by the
      neurosurgical service at the Thomas Jefferson University Hospital from May to
      December 2008. A standardized definition of minor and major complications was
      applied to all adverse events occurring within 30 days of surgery. Data on
      diagnosis, complications, and length of stay were retrospectively assessed using
      stepwise multivariate analysis. Patients were analyzed by preoperative diagnosis
      (neoplasm, infection, degenerative disease, trauma) and level of surgery
      (cervical or thoracolumbar). RESULTS: Total early complication incidence was
      53.2%, with a minor complication incidence of 46.4% and a major complication
      incidence of 21.3%. Preoperative diagnosis correlated only with the occurrence of
      minor complications in the overall cohort (p = 0.02). In patients undergoing
      surgery of the thoracolumbar spine, preoperative diagnosis correlated with
      presence of a complication and the number of complications (p = 0.003). Within
      this group, patients with preoperative diagnoses of infection and neoplasm were
      more often affected by isolated and multiple complications (p = 0.05 and p =
      0.02, respectively). Surgeries across the cervicothoracic and thoracolumbar
      junctions were associated with higher incidences of overall complication than
      cervical or lumbar surgery alone (p = 0.04 and p = 0.03, respectively). Median
      length of stay was 5 days for patients without a complication. Length of stay was
      significantly greater for patients with a minor complication (10 days, p <
      0.0001) and even greater for patients with a major complication (14 days, p <
      0.0001). CONCLUSIONS: The incidence of complications found in this prospective
      analysis is higher than that reported in previous studies. This association may
      be due to a greater accuracy of record-keeping, absence of recall bias via
      prospective data collection, high complexity of pathology and surgical
      approaches, or application of a more liberal definition of what constitutes a
      complication. Further large-scale prospective studies using clear definitions of
      complication are necessary to ascertain the true incidence of early postoperative
      complications in spine surgery.

PMID- 20809732
TI  - Micro-computed tomography-based highly automated 3D segmentation of the rat spine
      for quantitative analysis of metastatic disease.
AB  - Noninvasive evaluation of metastatic disease in the spine has generally been
      limited to 2D qualitative or semiquantitative analysis techniques. This study
      aims to develop and evaluate a highly automated micro-CT-based quantitative
      analysis tool that can measure the architectural impact of metastatic involvement
      in whole vertebrae. Micro-CT analysis of rat whole vertebrae was conducted using
      a combination of demons deformable registration, level set curvature evolution,
      and intensity based thresholding techniques along with upsampling and edge
      enhancement techniques. The algorithm was applied to 6 lumbar vertebrae (L1-3)
      from 6 rnu/rnu rats (3 healthy rats and 3 with metastatic involvement).
      Osteolytic metastatic involvement was modeled via MT1 human breast cancer cells.
      Excellent volumetric concurrency was achieved in comparing the automated micro-CT
      based segmentations of the whole vertebrae, trabecular centrums, and individual
      trabecular networks to manual segmentations (98.9%, 96.1%, and 98.3%,
      respectively; 6 specimens), and the automated segmentations were achieved in a
      fraction of the time. The algorithm successfully accounted for discontinuities in
      the cortical shell caused by vasculature and osteolytic destruction. As such,
      this work demonstrates the potential of this highly automated segmentation tool
      to permit rapid precise quantitative structural analysis of the spine with
      minimum user interaction in the analysis of both healthy and pathological
      (metastatically involved) vertebrae. Future optimization and the incorporation of
      lower-resolution imaging parameters may allow automated analysis of clinical CT
      based measures in addition to preclinical micro-CT-based analyses of the
      structural impact and progression of pathological processes in the spine.

PMID- 20809733
TI  - Diffusion tensor imaging tractography in patients with intramedullary tumors:
      comparison with intraoperative findings and value for prediction of tumor
      resectability.
AB  - OBJECT: The aim of this retrospective study was to evaluate the predictive value
      of diffusion tensor (DT) imaging with respect to resectability of intramedullary
      spinal cord tumors and to determine the concordance of this method with
      intraoperative surgical findings. METHODS: Diffusion tensor imaging was performed
      in 14 patients with intramedullary lesions of the spinal cord at different levels
      using a 3-T magnet. Routine MR imaging scans were also obtained, including
      unenhanced and enhanced T1-weighted images and T2-weighted images. Patients were
      classified according to the fiber course with respect to the lesion and their
      lesions were rated as resectable or nonresectable. These results were compared
      with the surgical findings (existence vs absence of cleavage plane). The
      interrater reliability was calculated using the kappa coefficient of Cohen.
      RESULTS: Of the 14 patients (7 male, 7 female; mean age 49.2 +/- 15.5 years), 13
      had tumors (8 ependymomas, 2 lymphomas, and 3 astrocytoma). One lesion was proven
      to be a multiple sclerosis plaque during further diagnostic workup. The lesions
      could be classified into 3 types according to the fiber course. In Type 1 (5
      cases) fibers did not pass through the solid lesion. In Type 2 (3 cases) some
      fibers crossed the lesion, but most of the lesion volume did not contain fibers.
      In Type 3 (6 cases) the fibers were completely encased by tumor. Based on these
      results, 6 tumors were considered resectable, 7 were not. During surgery, 7
      tumors showed a good cleavage plane, 6 did not. The interrater reliability (Cohen
      kappa) was calculated as 0.83 (p < 0.003), which is considered to represent
      substantial agreement. The mean duration of follow-up was 12.0 +/- 2.9. The
      median McCormick grade at the end of follow-up was II. CONCLUSIONS: These
      preliminary data suggest that DT imaging in patients with spinal cord tumors is
      capable of predicting the resectability of the lesion. A further prospective
      study is needed to confirm these results and any effect on patient outcome.

PMID- 20809734
TI  - Examining risk factors for posterior migration of fusion cages following
      transforaminal lumbar interbody fusion: a possible limitation of unilateral
      pedicle screw fixation.
AB  - OBJECT: Because the authors encountered 4 cases of hardware migration following
      transforaminal lumbar interbody fusion, a retrospective study was conducted to
      identify factors influencing the posterior migration of fusion cages. METHODS:
      Patients with lumbar degenerative disc disease (125 individuals; 144 disc levels)
      were treated using transforaminal lumbar interbody fusion and followed for 12-33
      months. Medical records and pre- and postoperative radiographs were reviewed, and
      factors influencing the incidence of cage migration were analyzed. RESULTS:
      Postoperative cage migration was found in 4 patients at or before 3 months.
      Because all the cages that migrated postoperatively were bullet-shaped
      (Capstone), only these cages were analyzed. The analysis of preoperative
      radiographs revealed that higher posterior disc height ([PDH] > or = 6 mm)
      significantly increased the incidence of postoperative cage migration, but
      percent slippage, translation, range of motion, and Cobb angle did not. The
      incidence of cage migration in patients with unilateral fixation (3 [8.3%] of 36)
      was not significantly different from that in patients with bilateral fixation (1
      [2.1%] of 48). Patients who had scoliotic curvature with a Cobb angle > 10
      degrees when treated with unilateral fixation demonstrated a tendency to have
      more frequent postoperative cage migration than patients treated with bilateral
      fixation. To examine the influence of the height of fusion cages, a value
      obtained by subtracting preoperative anterior disc height (ADH) or PDH from cage
      height was defined as "Cage height - ADH" (or "Cage height -PDH"). The analysis
      revealed that the value for "Cage height -ADH" as well as "Cage height -PDH" was
      significantly lower in migrated levels than in nonmigrated levels, suggesting
      that the choice of undersized cages may increase the incidence of cage migration.
      CONCLUSIONS: The results suggest that the use of a bullet-shaped cage, higher
      PDH, the presence of scoliotic curvature, and undersized fusion cages are
      possible risk factors for cage migration. One patient with postoperative cage
      migration following bilateral screw fixation underwent revision surgery, and the
      pedicle screw fixation was found to be disrupted. Other than in this patient,
      cage migration occurred only in those treated by unilateral fixation. The
      potential for postoperative cage migration and limitations of unilateral fixation
      should be considered by spine surgeons.

PMID- 20809735
TI  - Increased incidence of cage migration and nonunion in instrumented transforaminal
      lumbar interbody fusion with bioabsorbable cages.
AB  - OBJECT: Recent advances in the field of spinal implants have led to the
      development of the bioabsorbable interbody cage. Although much has been written
      about their advantageous characteristics, little has been reported regarding
      complications associated with these cages. The authors conducted this prospective
      cohort study to compare fusion and complication rates in patients undergoing
      transforaminal lumbar interbody fusion (TLIF) with carbon fiber cages versus
      biodegradable cages made from 70/30 poly(l-lactide-co-d,l-lactide) (PLDLA).
      METHODS: Between January 2005 and May 2006, 81 patients with various degenerative
      and/or structural pathologies affecting the lumbar spine underwent single- or
      multilevel TLIF with posterior segmental pedicle screw fixation using implants
      made of carbon fiber (37 patients) or 70/30 PLDLA (44 patients). Clinical and
      radiological follow-up was performed at 6 weeks, 3 months, 6 months, and 1 year,
      and is ongoing. The incidence of nonunion, screw breakage, and cage migration
      were compared between the 2 groups. RESULTS: There was no significant difference
      in demographic data between the 2 groups, the mean number of lumbar levels
      operated, or distribution of the levels operated. There was a significantly
      increased incidence of nonunion (8 patients, 18.2%) and cage migrations (8
      patients, 18.2%) in patients receiving the PLDLA implants compared with carbon
      fiber implants (no patients) (p = 0.006 and 0.007, respectively). There was no
      significant difference in demographic data between patients with cage migration
      and the rest of the patient population. Five of the 8 cases of migration occurred
      at the L5-S1 level while the remaining 3 occurred at the L4-5 level. The mean
      time to implant failure was 9.3 months. CONCLUSIONS: This study showed an
      increased incidence of nonunion (18.2%) and postsurgical cage migration (18.2%)
      in patients undergoing TLIF with biodegradable cages versus carbon fiber implants
      (0%) (p = 0.006 and 0.007, respectively).

PMID- 20809736
TI  - Reduction and transforaminal lumbar interbody fusion with posterior fixation
      versus transsacral cage fusion in situ with posterior fixation in the treatment
      of Grade 2 adult isthmic spondylolisthesis in the lumbosacral spine.
AB  - OBJECT: In situ transsacral fusion in the treatment of low-grade isthmic
      spondylolisthesis has rarely been reported. The authors treated 13 cases of L-5
      Grade 2 isthmic spondylolisthesis associated with collapsed disc space and
      osteoporosis by using transsacral fusion and fixation, and compared its clinical
      and radiological outcomes with the results of transforaminal lumbar interbody
      fusion (TLIF) and instrumental reduction in 21 patients. METHODS: The authors
      retrospectively analyzed 21 patients in Group A who were treated with reduction
      and TLIF, and 13 patients in Group B who were treated with transsacral cage
      fusion. Oswestry Disability Index and visual analog scale scores of back and leg
      pain were used to evaluate clinical outcomes. Radiological parameters for
      assessment included the percentage of slippage, whole lumbar lordosis, and
      lumbosacral angle. Operative data, fusion rate, and perioperative complications
      were recorded as well. RESULTS: The mean operation time and blood loss in Group B
      was less than that in Group A. Both groups realized good recovery from previous
      symptoms. The decrease in back and leg pain after surgery was significant within
      each group, without much difference between the 2 groups. No significant
      differences were found in lumbosacral angle, whole lumbar lordosis, visual analog
      scale score, and Oswestry Disability Index score between the 2 groups after
      surgery. The solid fusion rate was 95.2% in Group A and 92.3% in Group B. In
      Group A, 2 patients suffered from graft site pain, 1 had a superficial infection,
      and 1 had screw loosening; in Group B, dural tears were found in 2 patients,
      transient S-1 paresthesia in 2, and extensor hallucis longus muscle weakness in
      1. CONCLUSIONS: For patients with a collapsed disc space and poor bone quality,
      posterior in situ transsacral cage fusion may be used as an alternative to the
      TLIF procedure. The short-term clinical and radiological outcomes in the
      transsacral cage group were comparable with those in the TLIF group, although
      with a relatively higher neurological complication rate.

PMID- 20809737
TI  - Pedicle screws and great vessels.

PMID- 20809738
TI  - A retrospective analysis of pedicle screws in contact with the great vessels.
AB  - OBJECT: Pedicle screws placed in the thoracic, lumbar, and sacral spine
      occasionally come in contact with the aorta, vena cava, or iliac vessels. When
      such screws are seen on postoperative imaging in an asymptomatic patient, the
      surgeon must decide whether it is riskier to revise the screw or to observe it.
      The authors hypothesized that the incidence of screw placement causing
      perioperative vessel injury is low and, further, that screws placed in contact
      with major vessels do not always result in vessel injury. METHODS: A
      retrospective review of the operative records of 182 consecutive patients
      undergoing thoracic, lumbar, and lumbosacral pedicle screw fusion was performed
      to determine the frequency of intraoperative vessel injury. Postoperative imaging
      for 107 patients was available to determine the incidence of screws in contact
      with major vessels. Charts were examined to determine if any adverse sequelae had
      resulted from malpositioned screws. Patient outcomes were documented. RESULTS:
      There were no intraoperative vessel injuries or deaths in 182 consecutive
      operations. One hundred seven patients with available postoperative films had 680
      pedicle screws placed between T-3 and the sacrum during 115 operations. No
      patient had arterial screw penetration or deformation on postoperative imaging.
      Thirty-three of the 680 inserted screws were in contact with a major vessel on
      routine postoperative imaging. The contacted vessels included the aorta (4
      cases), the iliac artery (7 cases), and the iliac veins (22 cases). Patients were
      followed up until death or November 2009, for a mean follow-up of 44 months
      (median 44 months, range 5-109 months). None of the patients with vessel contact
      was noted to suffer symptoms or sequelae as a result of vessel contact.
      Radiographic follow-up as long as 50 months after surgery revealed no detectable
      vessel abnormality at the contacted site. CONCLUSIONS: Placing pedicle screws in
      contact with major vessels is a known risk of spinal surgery. The risk of
      repositioning a screw in contact with a major vessel but causing no symptoms must
      be weighed against the relative risk of leaving it in place.

PMID- 20809739
TI  - Osteoinductive bone graft substitutes for lumbar fusion.

PMID- 20809741
TI  - Uncemented custom femoral components in hip arthroplasty. A prospective clinical
      study of 191 hips followed for at least 7 years.
AB  - BACKGROUND AND PURPOSE: We have developed an individually designed, uncemented
      femoral component for achievement of improved strain distribution and fixation to
      the bone, to make uncemented stems more applicable in femurs of abnormal size and
      shape, and to improve the joint mechanics. Here we describe the design of the
      implant and present the results of a prospective clinical study with at least 7
      years of follow-up. PATIENTS AND METHODS: The prostheses are produced by CAD-CAM
      technique. The design of the stem is based on CT information, and the neck design
      is based on the surgeon's planning of the center of rotation, femoral head
      offset, and leg length correction. The first-generation stem produced before 2001
      had a proximal HA coating and a sand-blasted distal part that was down-scaled to
      avoid contact with compact bone. The second-generation stem had a porous coating
      beneath the HA layer and the distal part of the stem was polished. The implant
      was used in 762 hips (614 patients) from 1995 until 2009. 191 of these hips were
      followed for 7 years and 83 others were followed for 10 years, and these hips are
      included in the present study. Mean age at surgery was 48 (20-65) years.
      Congenital dysplasia of the hip was the reason for osteoarthritis in 46% and 57%
      of the hips in respective groups. Merle d'Aubigne score was recorded in 152 and
      75 hips in the two groups. Prostheses followed for 10 years, and almost all in
      the 7-year group, were first-generation stems. RESULTS: The 7- and 10-year
      cumulative revision rates were 1.1% and 2.4%, respectively, with stem revision
      for any reason as endpoint. The clinical results were similar at 7 and 10 years,
      with Merle d'Aubigne scores of 17. Intraoperative trochanteric fissures occurred
      in 2 of the 191 operations (1.0%); both healed after wiring. In hips followed for
      7 years, 2 periprosthetic fractures occurred; exchange of the stem was necessary
      in both. One additional fracture occurred between 7 and 10 years, and it was
      treated successfully with osteosynthesis. The rate of dislocation was 1.6% and
      2.4%, respectively. There was no radiographic loosening at follow-up.
      INTERPRETATION: Use of a custom femoral stem gives a reliable fixation and
      promising medium-term clinical results in femurs of normal and abnormal shape and
      dimension. The individual design, which enables optimized joint mechanics, gives
      a low risk of mechanical complications.

PMID- 20809740
TI  - Younger age increases the risk of early prosthesis failure following primary
      total knee replacement for osteoarthritis. A follow-up study of 32,019 total knee
      replacements in the Finnish Arthroplasty Register.
AB  - BACKGROUND AND PURPOSE: Total knee replacements (TKRs) are being increasingly
      performed in patients aged < or = 65 years who often have high physical demands.
      We investigated the relation between age of the patient and prosthesis survival
      following primary TKR using nationwide data collected from the Finnish
      Arthroplasty Register. MATERIALS: From Jan 1, 1997 through Dec 31, 2003, 32,019
      TKRs for primary or secondary osteoarthritis were reported to the Finnish
      Arthroplasty Register. The TKRs were followed until the end of 2004. During the
      follow-up, 909 TKRs were revised, 205 (23%) due to infection and 704 for other
      reasons. RESULTS: Crude overall implant survival improved with increasing age
      between the ages of 40 and 80. The 5-year survival rates were 92% and 95% in
      patients aged < or = 55 and 56-65 years, respectively, compared to 97% in
      patients who were > 65 years of age (p < 0.001). The difference was mainly
      attributable to reasons other than infections. Sex, diagnosis, type of TKR
      (condylar, constrained, or hinge), use of patellar component, and fixation method
      were also associated with higher revision rates. However, the differences in
      prosthesis survival between the age groups < or = 55, 56-65, and > 65 years
      remained after adjustment for these factors (p < 0.001). INTERPRETATION: Young
      age impairs the prognosis of TKR and is associated with increased revision rates
      for non-infectious reasons. Diagnosis, sex, type of TKR, use of patellar
      component, and fixation method partly explain the differences, but the effects of
      physical activity, patient demands, and obesity on implant survival in younger
      patients warrant further research.

PMID- 20809742
TI  - Cranial acetabular retroversion is common in developmental dysplasia of the hip
      as assessed by the weight bearing position.
AB  - BACKGROUND AND PURPOSE: The appearance of acetabular version differs between the
      supine and weight bearing positions in developmental dysplasia of the hip. Weight
      bearing radiographic evaluation has been recommended to ensure the best coherence
      between symptoms, functional appearance, and hip deformities. Previous prevalence
      estimates of acetabular retroversion in dysplastic hips have been established in
      radiographs recorded with the patient supine and with inclusion only if pelvic
      tilt met standardized criteria. We assessed the prevalence and the extent of
      acetabular retroversion in dysplastic hip joints in weight bearing pelvic
      radiographs. PATIENTS AND METHODS: We assessed 95 dysplastic hip joints (54
      patients) in weight bearing anteroposterior pelvic radiographs, measuring the
      acetabular height and the distance from the acetabular roof to the point of
      crossing of the acetabular rims, if present. RESULTS: Acetabular retroversion was
      found in 31 of 95 dysplastic hip joints. In 28 of 31 hip joints with
      retroversion, crossover of the acetabular rims was positioned within the cranial
      30% sector. The degree of pelvic tilt differed between retroverted and non
      retroverted dysplastic hip joints, though only reaching a statistically
      significant level in male dysplastic hip joints. INTERPRETATION: We identified
      cranial acetabular retroversion in one-third of dysplastic hip joints when
      assessed on weight bearing pelvic radiographs. If assessed on pelvic radiographs
      obtained with the patient supine, and with inclusion only if the degree of pelvic
      tilt meets standardized criteria, the prevalence of acetabular retroversion may
      be underestimated.

PMID- 20809743
TI  - Post-traumatic coxa vara in children following screw fixation of the femoral
      neck.
AB  - BACKGROUND AND PURPOSE: The rare displaced fractures of the femoral neck in
      children need accurate reduction and rigid fixation. The implants commonly used
      for internal fixation in children are pins or screws. We evaluated the long-term
      outcome in children who sustained fractures of the proximal femur that were
      treated by screw fixation. PATIENTS AND METHODS: All 22 children (mean age 12 (5
      16) years) with fractures of the femoral neck that were treated with screw
      fixation (mean 2.4 (1-3) screws) at our department between 1990 and 2006 were
      evaluated. For measurement of outcome, the Harris hip score (HHS) was used and
      the development of post-traumatic coxa vara was assessed from the difference in
      the neck-shaft angle postoperatively and at the latest follow-up examination,
      after mean 4 (2-15) years. RESULTS: A loss of reduction was observed in 12
      patients. There was a statistically significant correlation between the HHS and
      the changes in the neck-shaft angle. INTERPRETATION: Loss of reduction was found
      in more than half of the children. Screw fixation cannot be recommended for the
      treatment of femoral neck fractures in children due to a substantial number of
      post-traumatic coxa vara.

PMID- 20809744
TI  - Knee flexion influences periprosthetic BMD measurement in the tibia. Suggestions
      for a reproducible clinical scan protocol.
AB  - BACKGROUND AND PURPOSE: The quality and quantity of bone is important for the
      success of joint prostheses and may be monitored by dual energy X-ray
      absorptiometry (DXA). Available protocols suggest that the knee should be
      positioned in full extension. This is not possible for most patients in the first
      days after surgery; however, deficits in extension normalize with rehabilitation.
      Individual knee flexion between the baseline and follow-up investigations may
      therefore be different. We investigated the sensitivity of bone mineral density
      (BMD) measurements to knee flexion in a phantom study and in patients. We suggest
      a protocol for clinical use. METHODS: 2 phantom tibial bones with tibia
      components were secured in a clamp and BMD measurements were repeated 5 times at
      every 5 degrees change in flexion from 0 degrees to 20 degrees. For clinical use,
      a soft foam positioner was produced, in which the lower leg could be placed in
      neutral rotation and with the knee in approximately 25 degrees of flexion. The
      clinical repeatability was tested with double examinations in 38 patients. We
      investigated 3 regions of interest (ROIs) below the tibial plateau. RESULTS: In
      the phantom study, just 5 degrees of flexion was found to change the measured
      mean BMD. The reproducibility of clinical measurements (coefficient of variation)
      in the 3 ROIs assessed ranged from 1.8% to 3.7% for the anteroposterior scans,
      and from 3.4% to 6.2% for the lateral scans. INTERPRETATION: Knee flexion does
      affect the measured periprosthetic tibial BMD, and knee flexion should be the
      same at all clinical follow-ups. The protocol and soft foam positioner that we
      suggest permit precise and reliable assessment of BMD in the proximal tibia and
      they can be used in clinical work.

PMID- 20809745
TI  - Posterior cruciate ligament recruitment affects antero-posterior translation
      during flexion gap distraction in total knee replacement. An intraoperative study
      involving 50 patients.
AB  - BACKGROUND AND PURPOSE: Because of the oblique orientation of the posterior
      cruciate ligament (PCL), flexion gap distraction could lead to anterior movement
      of the tibia, which would influence the tibiofemoral contact point. This would
      affect the kinematics of the TKR. We assessed the flexion gap parameters when the
      knee is distracted during implantation of a PCL-retaining TKR. Furthermore, the
      effects of PCL elevation (steep or flat) and collateral ligament releases on the
      flexion gap parameters were determined. METHODS: During a ligament-guided TKR
      procedure in 50 knees, the flexion gap was distracted with a double-spring tensor
      with 200N after the tibia had been cut. The flexion gap height, anterior tibial
      translation, and femoral rotation were measured intraoperatively using a CT-free
      navigation system. RESULTS: During flexion gap distraction, the greatest
      displacement was seen in anterior-posterior direction. Mean ratio between
      increase in gap height and tibial translation was 1 to 1.9, and was highest for
      knees with a steep PCL (1 to 2.3). Knees with a flat PCL and knees with a
      ligament release had a larger increase in PCL elevation when the gap was
      distracted. INTERPRETATION: When the PCL is tensioned, every extra mm that the
      flexion gap is distracted can be expected to move the tibia anteriorly by at
      least 1.7 mm (flat PCL), or more if there is a steep PCL. This changes the
      tibiofemoral contact point, which may have consequences for polyethylene wear.

PMID- 20809746
TI  - Preoperative gait patterns and BMI are associated with tibial component
      migration.
AB  - BACKGROUND AND PURPOSE: There is no standard for patient triage in total knee
      arthroplasty (TKA) based on joint functional characteristics. This is largely due
      to the lack of objective postoperative measurement of success in TKA in terms of
      function and longevity, and the lack of knowledge of preoperative metrics that
      influence outcome. We examined the association between the preoperative
      mechanical environment of the patients knee joint during gait and the post-TKA
      stability of the tibial component as measured with radiostereometric analysis
      (RSA). METHODS: 37 subjects were recruited out of a larger randomized RSA trial.
      3-dimensional gait analysis was performed in the preoperative week. Longitudinal
      RSA data were gathered postoperatively at 6 months and 1 year. RESULTS: We found
      a statistically significant association between the pattern of the knee adduction
      moment during gait preoperatively and the total migration of the implant at 6
      months postoperatively. A substantial proportion of the variability in the total
      postoperative tibial component migration (R(2) = 0.45) was explained by a
      combination of implant type, preoperative knee joint loading patterns during
      gait, and body mass index at 6 months postoperatively. The relationships did not
      remain statistically significant at 1 year postoperatively. INTERPRETATION: Our
      findings support the hypothesis that preoperative functional characteristics of
      patients, and particularly joint loading patterns during activities of daily
      living, are important for outcome in TKA. This represents a first step in the
      development of predictive models of objective TKA outcome based on preoperative
      patient characteristics, which may lead to better treatment strategies.
      ClinicalTrials.gov (NCT00405379).

PMID- 20809747
TI  - Treatment of humeral shaft fractures--meta-analysis reupdated.

PMID- 20809748
TI  - Open reduction and internal fixation combined with hinged elbow fixator in
      capitellum and trochlea fractures.

PMID- 20809749
TI  - Lentiviral vector-mediated upregulation of let-7a inhibits gastric carcinoma cell
      growth in vitro and in vivo.
AB  - OBJECTIVE: Let-7a, a molecule that is reduced in various cancers, has been
      associated with cell growth and proliferation. Upregulation of let-7a may inhibit
      tumor cell growth. To verify this hypothesis, let-7a gene overexpression was
      studied in gastric cancer cells in vitro and in vivo. MATERIAL AND METHODS: A
      lentiviral system harboring both enhanced green fluorescent protein reporter gene
      and the let-7a short hairpin RNA expression cassette was firstly constructed.
      Then the stable let-7a gene overexpression SGC-7901 cells were established and
      real-time RT-PCR analysis was used to evaluate the expression of the let-7a gene.
      Their growth-inhibiting, cell cycle arrest characteristics were identified.
      RESULTS: In SGC-7901/let-7a cells, let-7a expression was significantly increased.
      Their proliferation was obviously retarded and the cell cycle changed with
      increased G0/G1 arrest and decreased S phase. In animal experiments, SGC-7901/let
      7a cell xenografts demonstrated growth suppression compared to parental or
      control gastric cancer cell xenografts. CONCLUSION: The results demonstrated that
      lentiviral vector was capable of upregulating let-7a, resulting in impressive
      anticancer effects. It offers a powerful new strategy for the development of
      novel therapeutic interventions to treat human gastric carcinomas.

PMID- 20809750
TI  - Differential angiogenesis function of CCM2 and CCM3 in cerebral cavernous
      malformations.
AB  - OBJECT: Loss-of-function mutations in CCM genes are frequently detected in
      familial cerebral cavernous malformations (CCMs). However, the current functional
      studies of the CCM genes in vitro have been performed mostly in commercially
      purchased normal cell lines and the results appeared discrepant. The fact that
      the cerebral vascular defects are rarely observed in CCM gene-deficient animals
      suggests the requirement of additional pathological background for the formation
      of vascular lesions. Consistent with these data, the authors assumed that
      silencing CCM genes in the endothelium derived from CCMs (CCM-ECs) serves as a
      unique and valuable model for investigating the function of the CCM genes in the
      pathogenesis of CCMs. To this end, the authors investigated the role and
      signaling of CCM2 and CCM3 in the key steps of angiogenesis using CCM-ECs.
      METHODS: Endothelial cells (ECs) derived from CCMs were isolated, purified, and
      cultured from the fresh operative specimens of sporadic CCMs (31 cases). The CCM2
      and CCM3 genes were silenced by the specific short interfering RNAs in CCM-ECs
      and in control cultures (human brain microvascular ECs and human umbilical vein
      ECs). The efficiency of gene silencing was proven by real-time reverse
      transcriptase polymerase chain reaction. Cell proliferation and apoptosis,
      migration, tube formation, and the expression of phosphor-p38, phosphor-Akt, and
      phosphor-extracellular signal-regulated kinase-1 and 2 (ERK1/2) were analyzed
      under CCM2 and CCM3 silenced conditions in CCM-ECs. RESULTS: The CCM3 silencing
      significantly promoted proliferation and reduced apoptosis in all 3 types of
      endothelium, but accelerated cell migration exclusively in CCM-ECs.
      Interestingly, CCM2 siRNA influenced neither cell proliferation nor migration.
      Silencing of CCM3, and to a lesser extent CCM2, stimulated the growth and
      extension of sprouts selectively in CCM-ECs. Loss of CCM2 or CCM3 did not
      significantly influence the formation of the tubelike structure. However, the
      maintenance of tube stability was largely impaired by CCM2, but not CCM3,
      silencing. Western blot analysis revealed that CCM2 and CCM3 silencing commonly
      activated p38, Akt, and ERK1/2 in CCM-ECs. CONCLUSIONS: The unique response of
      CCM-ECs to CCM2 or CCM3 siRNA indicates that silencing CCM genes in CCM-ECs is
      valuable for further studies on the pathogenesis of CCMs. Using this model
      system, the authors demonstrate a distinct role of CCM2 and CCM3 in modulating
      the different processes of angiogenesis. The stimulation of endothelial
      proliferation, migration, and massively growing and branching angiogenic sprouts
      after CCM3 silencing may potentially contribute to the formation of enriched
      capillary-like immature vessels in CCM lesions. The severe impairment of the tube
      integrity by CCM2, but not CCM3, silencing is associated with the different
      intracranial hemorrhage rate observed from CCM2 and CCM3 mutation carriers. The
      activation of p38, ERK1/2, and Akt signal proteins in CCM2- or CCM3-silenced CCM
      ECs suggests a possible involvement of these common pathways in the pathogenesis
      of CCMs. However, the specific signaling mediating the distinct function of CCM
      genes in the pathogenesis of CCMs needs to be further elucidated.

PMID- 20809751
TI  - Operative management of brainstem cavernous malformations.
AB  - Brainstem cavernous malformations (CMs) are complex lesions associated with
      hemorrhage and neurological deficit. In this review, the authors describe the
      anatomical nuances relating to the operative techniques for these challenging
      lesions. The resection of brainstem CMs in properly selected patients has been
      demonstrated to reduce the risk of rehemorrhage and can be achieved relatively
      safely in experienced hands.

PMID- 20809752
TI  - Stereotactic radiosurgery for the treatment of symptomatic brainstem cavernous
      malformations.
AB  - OBJECT: The authors performed a retrospective review of prospectively collected
      data to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) for
      the treatment of patients harboring symptomatic solitary cavernous malformations
      (CMs) of the brainstem that bleed repeatedly and are high risk for resection.
      METHODS: Between 1988 and 2005, 68 patients (34 males and 34 females) with
      solitary, symptomatic CMs of the brainstem underwent Gamma Knife surgery. The
      mean patient age was 41.2 years, and all patients had suffered at least 2
      symptomatic hemorrhages (range 2-12 events) before radiosurgery. Prior to SRS, 15
      patients (22.1%) had undergone attempted resection. The mean volume of the
      malformation treated was 1.19 ml, and the mean prescribed marginal radiation dose
      was 16 Gy. RESULTS: The mean follow-up period was 5.2 years (range 0.6-12.4
      years). The pre-SRS annual hemorrhage rate was 32.38%, or 125 hemorrhages,
      excluding the first hemorrhage, over a total of 386 patient-years. Following SRS,
      11 hemorrhages were observed within the first 2 years of follow-up (8.22% annual
      hemorrhage rate) and 3 hemorrhages were observed in the period after the first 2
      years of follow-up (1.37% annual hemorrhage rate). A significant reduction (p <
      0.0001) in the risk of brainstem CM hemorrhages was observed following
      radiosurgical treatment, as well as in latency period of 2 years after SRS (p <
      0.0447). Eight patients (11.8%) experienced new neurological deficits as a result
      of adverse radiation effects following SRS. CONCLUSIONS: The results of this
      study support a role for the use of SRS for symptomatic CMs of the brainstem, as
      it is relatively safe and appears to reduce rebleeding rates in this high
      surgical-risk location.

PMID- 20809754
TI  - Prognostic factors for the outcome of surgical and conservative treatment of
      symptomatic spinal cord cavernous malformations: a review of a series of 20
      patients.
AB  - OBJECT: In this study, the authors present a review of a series of 20
      intramedullary spinal cord cavernous malformations (SCCMs) with particular focus
      on MR imaging and prognostic factors. METHODS: Between 1994 and 2009, 20 patients
      with SCCM were treated under the care of the senior author. The diagnosis was
      made in all patients after the onset of clinical symptoms. The age of the 9 men
      and 11 women ranged between 26 and 71 years (median 38.5 years). The duration of
      symptoms prior to referral ranged from 1 week to 9 years (median 6.5 months). At
      the time of referral, 4 patients had no significant neurological deficits, 10
      patients suffered significant functional restrictions, and 6 patients presented
      with severe paraparesis and loss of functional strength. None of the patients had
      complete paraplegia. Seventeen patients underwent microsurgical removal, while 3
      patients opted for conservative therapy. For the present analysis, the medical
      records and MR images and/or reports were reviewed. Classification of length of
      history, pretreatment status, MR imaging pattern, and treatment modality was done
      and correlated with outcome. RESULTS: The cavernoma was located at the cervical
      level in 8 patients and between T-1 and L-1 in 12 patients. The cavernoma
      appeared as mainly T2 hyperintense on MR images in 7 patients, mainly T2
      hypointense in 2 patients, and mixed in the remaining 10 patients. The
      craniocaudal extension of the core varied between 5 and 45 mm. In 2 patients with
      cervical cavernomas, a distinct T2 signal of the spinal cord cranial and distal
      to the cavernoma was seen, and in a patient with a large thoracic cavernoma, T2
      extinction cranial and caudal to the cavernoma was seen as a sign of
      hemosiderosis. Neurological deficits improved postoperatively in 12 of the
      surgically treated patients, remained stable in 2, and deteriorated in 3. The 3
      patients who were conservatively treated remained stable over a follow-up of 3-9
      years. Postoperative improvement was seen in 5 of 7 surgical patients with a
      history of symptoms of 2 months or less, 5 of 6 patients with a history of 2-24
      months, and in 2 of 4 patients with a history of more than 2 years. Two of the 3
      patients with postoperative deterioration had a history of more than 2 years and
      the third a short history of 1 month. CONCLUSIONS: Although a satisfactory
      outcome can be achieved through surgical treatment of SCCMs, some patients worsen
      after surgery or during the postoperative course. Long-term stability is possible
      in oligosymptomatic conservatively treated patients. The prevalence and
      pathophysiological importance of segmental spinal cord edema and hemosiderosis is
      incompletely understood at the present time.

PMID- 20809753
TI  - Clinical presentation and surgical management of intramedullary spinal cord
      cavernous malformations.
AB  - OBJECT: Intramedullary cavernous malformation (CM) is a rare entity, accounting
      for 5% of all intraspinal lesions. The objective in this study was to define the
      clinical characteristics of this disease, detail the surgical approach and
      technique, and present the clinical outcome. METHODS: Retrospective chart review
      was performed in 22 patients with histologically confirmed CMs. The authors used
      a laminectomy approach for midline dorsal lesions, with unilateral radical
      facetectomy and dentate ligament resection for laterally or ventrally located
      lesions. Patient profiles, operative indications, surgical approaches, operative
      findings, complications, and long-term follow-up were reviewed. RESULTS: The
      average age of patients in the cohort was 43 +/- 14 years, the average duration
      of symptoms was 7 +/- 7 months, and the average follow-up was 6 +/- 4 years. The
      average size of the lesion was 1 +/- 0.4 cm, the average surgical time was 4 +/-
      0.96 hours, and the average estimated blood loss was 350 +/- 131 ml. The rate of
      complication was 5% (1 patient; due to a wound infection). According to the
      McCormick classification, the score for the cohort was 1.8 +/- 1.2
      preoperatively, 2.1 +/- 1.2 postoperatively, and 1.3 +/- 0.65 at late follow-up.
      (All preceding values are given as the mean +/- SD.) There was a significant
      neurological improvement at follow-up compared with the preoperative state (p <
      0.05). The majority of patients (50%) had a stable outcome compared with their
      preoperative state, with a large proportion (41%) having an improved outcome. A
      minority of patients (9%) had a worsened outcome due to dysesthetic pain.
      Patients with dysesthesia had a longer duration of clinical symptoms prior to
      surgery compared with patients without dysesthesia (p < 0.05). CONCLUSIONS: The
      authors demonstrated the safety, efficacy, and durability of their surgical
      approach for resection of spinal intramedullary CM. Proper examination,
      preoperative imaging, and prompt surgical intervention were necessary for a
      satisfactory outcome.

PMID- 20809755
TI  - Intramedullary spinal cord cavernous malformations.
AB  - Although originally the subject of rare case reports, intramedullary spinal cord
      cavernous malformations (CMs) have recently surfaced in an increasing number of
      case series and natural history reports in the literature. The authors reviewed
      27 publications with 352 patients to consolidate modern epidemiological, natural
      history, and clinical and surgical data to facilitate decision making when
      managing these challenging vascular malformations. The mean age at presentation
      was 42 years without a sex predilection. Thirty-eight percent of the cases were
      cervical, 57% thoracic, 4% lumbar, and 1% unspecified location. Nine percent of
      the patients had a family history of CNS CMs. Twenty-seven percent of the
      patients had an associated cranial CM. On presentation 63% of the patients had
      motor deficits, 65% had sensory deficits, 27% had pain, and 11% had bowel or
      bladder dysfunction. Presentation was acute in 30%, recurrent in 16%, and
      progressive in 54% of cases. An overall annual hemorrhage rate was calculated as
      2.5% for 92 patients followed up for a total of 2571 patient-years. Across 24
      reviewed surgical series, a 91% complete resection rate was found. Transient
      morbidity was seen in 36% of cases. Sixty-one percent of patients improved, 27%
      were unchanged, and 12% were worse at the long-term follow-up. Using this
      information, the authors review surgical nuances in treating these lesions and
      propose a management algorithm.

PMID- 20809756
TI  - Pain outcomes after surgery in patients with intramedullary spinal cord cavernous
      malformations.
AB  - OBJECT: The objective of the study was to quantify the improvement in pain levels
      for patients who have undergone surgery for intramedullary spinal cord cavernous
      malformations (SCCMs). METHODS: The author reviewed medical records of patients
      who underwent surgery for an intramedullary SCCM between 2003 and 2010. Numerical
      pain scores (range 0-10) were recorded preoperatively and at follow-up. The
      follow-up period exceeded 1 year. Neurological status and subjective outcomes
      were assessed. Each patient underwent follow-up MR imaging. RESULTS: Five
      patients were identified with SCCMs who underwent surgery: 4 with thoracic and 1
      with cervical lesions. Patients had been conservatively managed for an average of
      5 years prior to surgery, and none had a history of acute hemorrhage or
      neurological deterioration during the observation period. The primary indication
      for surgery in each patient was pain, although 4 of 5 patients had some evidence
      of myelopathy on examination. Pain improved from a mean preoperative score of 8.6
      to mean score of 2.0 (p < 0.01) at 1 month. Pain scores then increased to 3.7 (p
      < 0.01) at 1 year. All patients had some improvement in pain. No new motor
      weakness was noted, but all patients had increased symptoms of posterior-column
      dysfunction and numbness after surgery. CONCLUSIONS: Spinal cord intramedullary
      cavernous malformations are increasingly being diagnosed early with patients
      presenting with mostly pain symptoms. Removal of the lesion is reliably
      associated with improvement in pain scores but often the pain improvement is
      transient. While long-term worsening of pain scores occurs, at 1-year follow-up,
      patients reported pain scores were improved over preoperative scores. In all
      patients some degree of postoperative posterior-column dysfunction was present.
      Some of the immediate pain relief may be due to analgesia related to the
      myelotomy of newly described posterior column pain pathways. In patients with
      severe pain, surgery to remove SCCMs reduced the overall pain level at 1 year.

PMID- 20809757
TI  - Patient-assessed satisfaction and outcome after microsurgical resection of
      cavernomas causing epilepsy.
AB  - OBJECT: Microsurgical resection of supratentorial cavernomas associated with
      intractable epilepsy is performed frequently. Despite its common occurrence,
      little is known about patient perceptions of microsurgical resection for
      cavernomas. This survey study was performed to investigate patient perceived
      outcome after surgery for cavernomas associated with intractable epilepsy.
      METHODS: The authors' surgical database was searched for cavernoma resection
      performed between 1971 and July of 2006. Of the initial 173 patients identified,
      102 met criteria for medically intractable seizures. These 102 patients were then
      mailed a survey to determine follow-up and patient satisfaction. Thirty-nine
      surveys were returned as undeliverable, and 30 (48%) of the remaining 63 patients
      responded. RESULTS: The average age at surgery for patients responding to this
      survey was 40 +/- 16 years compared with 35 +/- 15 years for all 102 patients. At
      prolonged follow-up, 87% of patients reported being seizure-free. Of those with
      seizures, 2 (7%) reported being nearly seizure-free (rare disabling seizures), 2
      (7%) believed they had a worthwhile improvement in seizure frequency, and no
      patient (0%) in this series believed they did not have a worthwhile improvement
      in seizure frequency. Ninety percent of responders stated they definitely, and
      10% probably, would have surgery again. No patient responded that they probably
      or definitely would not have epilepsy surgery. Mean clinical follow-up was 36 +/-
      8 months and survey follow-up was 97 +/- 13 months for these 30 patients. Use of
      the mail-in survey increased follow-up length 2.7 times longer compared with
      clinical follow-up. CONCLUSIONS: It is clear from this select group of survey
      responders that patients undergoing surgery for cavernomas associated with
      medically intractable epilepsy are happy they underwent surgery (100%) and had
      excellent surgical outcomes (87% seizure-free) at prolonged follow-up of 97 +/-
      13 months. These survey results support that microsurgical resection for
      cavernomas is highly effective and significantly improves these patients' quality
      of life.

PMID- 20809758
TI  - Cavernous malformations of the optic pathway and hypothalamus: analysis of 65
      cases in the literature.
AB  - OBJECT: Cavernous malformations (CMs) of the optic pathway and hypothalamus (OPH)
      are extremely rare. Patients with these lesions typically present with chiasmal
      apoplexy, characterized by sudden visual loss, acute headaches, retroorbital
      pain, and nausea. Surgical removal is the recommended treatment to restore or
      preserve vision and to eliminate the risk of future hemorrhage. However, the
      anatomical location and eloquence of nearby neural structures can make these
      lesions difficult to access and remove. In this study, the authors review the
      literature for reported cases of OPH CMs to analyze clinical and radiographic
      presentations as well as surgical approaches and neurological outcomes. METHODS:
      A MEDLINE/PubMed search was performed, revealing 64 cases of OPH CMs. The authors
      report an additional case in the study, making a total of 65 cases. Each case was
      analyzed for clinical presentation, lesion location, radiographic features,
      treatment method, and visual outcome. RESULTS: In 65 patients with OPH CMs, the
      optic chiasm was affected in 54 cases, the optic nerve(s) in 35, the optic tract
      in 13, and the hypothalamus in 5. Loss of visual field and acuity was the most
      common presenting symptom (98%), followed by headache (60%). The onset of
      symptoms was acute in 58% of patients, subacute in 15%, and chronic progressive
      in 26%. Computed tomography scans revealed hyperdense suprasellar lesions, with
      calcification visible in 56% of cases. Magnetic resonance imaging typically
      demonstrated a heterogeneous lesion with mixed signal intensities suggestive of
      blood of different ages. The lesion was often surrounded by a peripheral rim of
      hypointensity on T2-weighted images in 60% of cases. Minimal or no enhancement
      occurred after the administration of gadolinium. Hemorrhage was reported in 82%
      of cases. Most patients were surgically treated (97%) using gross-total resection
      (60%), subtotal resection (6%), biopsy procedure alone (6%), biopsy procedure
      with decompression (23%), and biopsy procedure followed by radiation (2%). Those
      patients who underwent gross-total resection had the highest rate of visual
      improvement (85%). Two patients were treated conservatively, resulting in
      complete blindness in 1 patient and spontaneous recovery of vision in the other
      patient. CONCLUSIONS: Cavernous malformations of the OPH are rare and challenging
      lesions. Gross-total resection of these lesions is associated with favorable
      visual outcomes. Emergent surgery is warranted in patients presenting with
      chiasmal apoplexy to prevent permanent damage to the visual pathway.

PMID- 20809759
TI  - Giant posterior fossa cavernous malformations in 2 infants with familial cerebral
      cavernomatosis: the case for early screening.
AB  - The author reports the details in 2 cases of infants with familial cerebral
      cavernomatosis who presented in dire condition from hemorrhagic posterior fossa
      cavernous malformations. In Case 1, a 4-month-old boy presented with
      opisthotonos, gaze palsy, and lethargy. Magnetic resonance imaging revealed a
      multilobulated cavernous malformation in the fourth ventricle with evidence of
      bleeding and obstructive hydrocephalus. In Case 2, a 7-month-old girl presented
      with lethargy, followed by rapid neurological decline. Imaging demonstrated a
      large lesion involving both the brainstem and cerebellum, with obstructive
      hydrocephalus. Both patients required immediate surgical intervention, and
      external ventricular drainage and posterior fossa craniotomies were performed.
      Both patients made excellent recoveries. These cases suggest that infants in
      families with suspected or confirmed familial cerebral cavernomatosis should be
      screened at an early age.

PMID- 20809760
TI  - The pathogenetic features of cerebral cavernous malformations: a comprehensive
      review with therapeutic implications.
AB  - Cerebral cavernous malformations (CCMs) are common vascular lesions of the CNS
      that may lead to seizures, focal neurological deficits, and fatal hemorrhagic
      stroke. Human genetic studies have identified 3 genes associated with CCM, and
      biochemical and molecular studies in mice have elucidated signaling pathways with
      important therapeutic implications. In this review, the authors shed light on the
      3 discovered CCM genes as well as their protein products, with particular
      emphasis on their signal transduction pathways and their interaction with one
      another. Close focus is directed at mice model studies involving the Ccm2 gene
      product signaling pathway, revealing an important role for the use of simvastatin
      or other RhoA inhibitors as a therapeutic modality in the treatment of CCM. The
      remaining challenges to creating a more faithful CCM animal model as well as
      future clinical and research implications are reviewed.

PMID- 20809761
TI  - Upregulation of transmembrane endothelial junction proteins in human cerebral
      cavernous malformations.
AB  - OBJECT: Cerebral cavernous malformations (CCMs) are among the most prevalent
      cerebrovascular malformations, and endothelial cells seem to play a major role in
      the disease. However, the underlying mechanisms, including endothelial
      intercellular communication, have not yet been fully elucidated. In this article,
      the authors focus on the endothelial junction proteins CD31, VE-cadherin, and
      occludin as important factors for functional cell-cell contacts known as vascular
      adhesion molecules and adherence and tight junctions. METHODS: Thirteen human CCM
      specimens and 6 control tissue specimens were cryopreserved and examined for the
      presence of VE-cadherin, occludin, and CD31 by immunofluorescence staining.
      Protein quantification was performed by triplicate measurements using western
      blot analysis. RESULTS: Immunofluorescent analyses of the CCM sections revealed a
      discontinuous pattern of dilated microvessels and capillaries as well as
      increased expression of occludin, VE-cadherin, and CD31 in the intima and in the
      enclosed parenchymal tissue compared with controls. Protein quantification
      confirmed these findings by showing upregulation of the levels of these proteins
      up to 2-6 times. CONCLUSIONS: A protocol enabling the molecular and morphological
      examination of the intercellular contact proteins in human CCM was validated. The
      abnormal and discontinuous pattern in these endothelial cell-contact proteins
      compared with control tissue explains the loose intercellular junctions that are
      considered to be one of the causes of CCM-associated bleeding or transendothelial
      oozing of erythrocytes. Despite the small number of specimens, this study
      demonstrates for the first time a quantitative analysis of endothelial junction
      proteins in human CCM.

PMID- 20809762
TI  - Cerebral cavernous malformations as a disease of vascular permeability: from
      bench to bedside with caution.
AB  - Tremendous insight into the molecular and genetic pathogenesis of cerebral
      cavernous malformations (CCMs) has been gained over the past 2 decades. This
      includes the identification of 3 distinct genes involved in familial CCMs. Still,
      a number of unanswered questions regarding the process from gene mutation to
      vascular malformation remain. It is becoming more evident that the disruption of
      interendothelial junctions and ensuing vascular hyperpermeability play a
      principal role. The purpose of this review is to summarize the current
      understanding of CCM genes, associated proteins, and functional pathways.
      Promising molecular and genetic therapies targeted at identified molecular
      aberrations are discussed as well.

PMID- 20809763
TI  - Susceptibility weighted magnetic resonance imaging of cerebral cavernous
      malformations: prospects, drawbacks, and first experience at ultra-high field
      strength (7-Tesla) magnetic resonance imaging.
AB  - High-resolution susceptibility weighted MR imaging at high field strength
      provides excellent depiction of venous structures, blood products, and iron
      deposits, making it a promising complementary imaging modality for cerebral
      cavernous malformations (CCMs). Although already introduced in 1997 and being
      constantly improved, susceptibility weighted imaging is not yet routine in
      clinical neuroimaging protocols for CCMs. In this article, the authors review the
      recent literature dealing with clinical and scientific susceptibility weighted
      imaging of CCMs to summarize its prospects and drawbacks and provide their first
      experience with its use in ultra-high field (7-T) MR imaging.

PMID- 20809765
TI  - Update on the natural history of cavernous malformations and factors predicting
      aggressive clinical presentation.
AB  - Cavernous malformations (CMs) are angiographically occult, low-pressure
      neurovascular lesions with distinct imaging and clinical characteristics. They
      present with seizure, neurological compromise due to lesion hemorrhage or
      expansion, or as incidental findings on neuroimaging studies. Treatment options
      include conservative therapy, medical management of seizures, surgical
      intervention for lesion resection, and in select cases stereotactic radiosurgery.
      Optimal management requires a thorough understanding of the natural history of
      CMs including consideration of issues such as mode of presentation, lesion
      location, and genetics that may impact the associated neurological risk. Over the
      past 2 decades, multiple studies have been published, shedding valuable light on
      the clinical characteristics and natural history of these malformations. The
      purpose of this review is to provide the reader with a concise consolidation of
      this published material such that they may better understand the risks associated
      with CMs and their implications on patient treatment.

PMID- 20809766
TI  - Surgical approaches to brainstem cavernous malformations.
AB  - Brainstem cavernous malformations (CMs) are low-flow vascular lesions in eloquent
      locations. Their presentation is often marked with symptomatic hemorrhages that
      appear to occur more frequently than hemorrhage from supratentorial cavernomas.
      Brainstem CMs can be removed using 1 of the 5 standard skull-base approaches:
      retrosigmoid, suboccipital (with or without telovelar approach), supracerebellar
      infratentorial, orbitozygomatic, and far lateral. Patients being referred to a
      tertiary institution often have lesions that are aggressive with respect to
      bleeding rates. Nonetheless, the indications for surgery, in the authors'
      opinion, are the same for all lesions: those that are symptomatic, those that
      cause mass effect, or those that abut a pial surface. Patients often have
      relapsing and remitting courses of symptoms, with each hemorrhage causing a
      progressive and stepwise decline. Many patients experience new postoperative
      deficits, most of which are transient and resolve fully. Despite the risks
      associated with operating in this highly eloquent tissue, most patients have had
      favorable outcomes in the authors' experience. Surgical treatment of brainstem
      CMs protects patients from the potentially devastating effects of rehemorrhage,
      and the authors believe that the benefits of intervention outweigh the risks in
      patients with the appropriate indications.

PMID- 20809764
TI  - Emerging clinical imaging techniques for cerebral cavernous malformations: a
      systematic review.
AB  - Cerebral cavernous malformations (CCMs) are divided into sporadic and familial
      forms. For clinical imaging, T2-weighted gradient-echo sequences have been shown
      to be more sensitive than conventional sequences. Recently more advanced imaging
      techniques such as high-field and susceptibility-weighted MR imaging have been
      employed for the evaluation of CCMs. Furthermore, diffusion tensor imaging and
      functional MR imaging have been applied to the preoperative and intraoperative
      management of these lesions. In this paper, the authors attempt to provide a
      concise review of the emerging imaging methods used in the clinical diagnosis and
      treatment of CCMs.

PMID- 20809767
TI  - Brainstem cavernous malformations: anatomical, clinical, and surgical
      considerations.
AB  - Symptomatic brainstem cavernous malformations carry a high risk of permanent
      neurological deficit related to recurrent hemorrhage, which justifies aggressive
      management. Detailed knowledge of the microscopic and surface anatomy is
      important for understanding the clinical presentation, predicting possible
      surgical complications, and formulating an adequate surgical plan. In this
      article the authors review and illustrate the surgical and microscopic anatomy of
      the brainstem, provide anatomoclinical correlations, and illustrate a few
      clinical cases of cavernous malformations in the most common brainstem areas.

PMID- 20809768
TI  - Swedish women with coeliac disease in remission use more health care services
      than other women: a controlled study.
AB  - OBJECTIVE: To examine whether the perceived poor outcome of dietary treatment
      makes Swedish women with coeliac disease (CD) prone to use more health care
      services than other women. MATERIAL AND METHODS: The health care consumption over
      36 consecutive months was examined for 137 Swedish women aged 20-80 years with CD
      in remission after living on a gluten-free diet for a median of 4 years (range 1
      8 years). Comparisons were made with the health care consumption of 411 women in
      the general population matched for age and residence. RESULTS: The results show
      that women with CD use health care services annually a median of 5.0 times (range
      0-76) that is more than female controls 3.6 (0-311) (p < 0.05) mainly in primary
      care and for complaints related to mental and behavioral disorders (ICD F),
      diseases of the digestive system (ICD K) and diseases of the musculoskeletal
      system and connective tissue (ICD M). CONCLUSIONS: Women with CD used health care
      services in keeping with studies indicating reduced health-related quality of
      life of people with this condition. The results provide evidence that women with
      CD in remission suffer from co-morbidities that may signal a need for a
      multidisciplinary follow-up of subjects with CD in Sweden.

PMID- 20809769
TI  - An analysis of the human and mouse CXCR5 gene introns.
AB  - Both mouse and human chemokine receptor CXC motif 5 (CXCR5) genes exhibit one
      single intron interrupting the coding sequence. The mouse intron is 12053
      nucleotides (nt) long; the human intron is 9603 nt long. Sections of the mouse
      intron significantly align plus/plus with sections of the human intron; the
      aligned segments are in the same order in mouse as in man and overall cover 13%
      of the mouse sequence and 17% of the human sequence. The human CXCR5 intron
      harbors sequences derived from retroviruses (human endogenous retroviruses). The
      mouse intron comprises very similar sequences. About 70% of the mouse intron
      sequence is 'specific' to this gene, while sequences in the rest of the intron
      are shared with many other genes located on different chromosomes. In the human
      the coverage by specific sequences is about 87%. Thus, the contribution of
      transposable elements is significantly higher in mouse (30%) than in man (13%).
      Intra-intronic plus/minus alignments exist in mouse (10 couples) and man (two
      couples): these may form stem and loop structures determining the secondary
      structure of the corresponding pre-mRNAs.

PMID- 20809770
TI  - Surgical rates in ulcerative colitis: have we made a difference?

PMID- 20809771
TI  - Serum levels of omentin, chemerin and adipsin in patients with biopsy-proven
      nonalcoholic fatty liver disease.
AB  - OBJECTIVE: The novel adipokines omentin, chemerin, and adipsin are associated
      with insulin resistance and the components of the metabolic syndrome. We assayed
      circulating levels of these molecules and examined their association with
      clinical, biochemical, and histological phenotypes in patients with nonalcoholic
      fatty liver disease (NAFLD). MATERIAL AND METHODS: Serum levels of omentin,
      chemerin, and adipsin were assayed by enzyme-linked immunosorbent assay in 99
      patients with biopsy-proven NAFLD and 75 control subjects. We analyzed
      associations between adipokines and the characteristics of patients with NAFLD
      using multivariable linear regression models. RESULTS: Adipsin levels did not
      differ between patients and controls, whereas both omentin and chemerin levels
      were significantly higher in patients with biopsy-proven NAFLD than in controls
      (both p values <0.001). Serum omentin levels were significantly associated with C
      reactive protein (r = 0.29, p < 0.01) and the degree of hepatocyte ballooning (r
      = 0.27, p < 0.01), whereas chemerin showed a modest association with liver
      fibrosis (r = 0.22, p = 0.04). After stepwise linear regression analysis
      adjusting for potential confounders, serum omentin levels retained their
      independent significance as a predictor of hepatocyte ballooning in patients with
      NAFLD (beta = 1.42; t = 2.79, p < 0.01). CONCLUSIONS: Our results suggest that
      serum omentin levels are raised in patients with NAFLD regardless of potential
      confounders and represent an independent predictor of hepatocyte ballooning.

PMID- 20809772
TI  - A case report of a patient with Pfeiffer syndrome, an FGRF 2 mutation (Trp290Cys)
      and unique ocular anterior segment findings.
AB  - PURPOSE: To report a case of a child with Pfeiffer syndrome, unique ocular
      anterior segment findings and a mutation in FGFR2 (Trp290Cys). METHODS: Case
      Report. RESULTS: We describe a patient with Pfeiffer syndrome with a unique
      constellation of ocular anterior segment anomalies including microcornea, limbal
      scleralization, corectopia and glaucoma. Genomic DNA extraction was heterozygous
      for a G to T mutation at nucleotide 870 of the fibroblast growth factor receptor
      2 gene (FGFR2) which changes tryptophan (TGG) to cysteine (TGT) at amino acid
      position 290 (Trp290Cys). CONCLUSION: This case supports the association between
      Pfeiffer syndrome and severe ocular anterior segment anomalies, including
      glaucoma, and underscores the possible role that FGFR2 has in development of the
      anterior segment of the eye.

PMID- 20809773
TI  - The influence of early embryo traits on human embryonic stem cell derivation
      efficiency.
AB  - Despite its prognostic value in in vitro fertilization, early embryo morphology
      is not reported on in the derivation of human embryonic stem cell (hESC) lines.
      Standard hESC derivation does rely on blastocyst development and its efficiency
      is highly correlated to inner cell mass (ICM) quality. Poor-quality embryos
      (PQEs) donated for hESC derivation may have a range of cleavage-stage
      abnormalities that are known to compromise further development. This study was
      implemented to determine whether specific PQEs traits influence the efficiency of
      good-quality ICMs to derive new hESC lines. We found that although the types of
      PQEs investigated were all able to make blastocysts with good-quality ICMs, the
      ICMs were unequal in their ability to derive hESCs. Good-quality ICMs from
      embryos with multiple poor-quality traits were unable to generate hESC lines, in
      contrast to good-quality ICMs from embryos with a single poor-quality trait. In
      addition, our data suggest a direct correlation between the number of ICM cells
      present in the blastocyst and its capacity to derive new hESC lines. This study
      is the first to demonstrate that ICM quality alone is an incomplete indicator of
      hESC derivation and that application of in vitro fertilization-based early embryo
      scoring can help predict hESC derivation efficiency. Experiments aiming to
      quantify, improve upon, or compare hESC derivation efficiency should thus take
      into consideration early embryo morphology scoring for the comparison of groups
      with equal developmental competence.

PMID- 20809774
TI  - Historical evolution in the understanding of Stargardt macular dystrophy.
AB  - The historical evolution in the understanding of Stargardt macular dystrophy
      (fundus flavimaculatus) from the initial description by Karl Stargardt,
      identification of mutations in the ABCA4 gene, to the development of a mouse
      model for the human disease, is described. Highlighted are the studies by several
      investigators whose contributions illuminated the path to our current
      understanding of Stargardt disease and helped to advance progress toward future
      therapeutic trials for the unfortunate group of patients afflicted with this
      disease.

PMID- 20809776
TI  - Endothelial nitric oxide synthase genotypes in the etiology of retinopathy of
      prematurity in premature infants.
AB  - PURPOSE: Retinopathy of Prematurity (ROP) is a vasoproliferative disorder
      affecting preterm infants leading to visual impairment. ROP is more common in
      Caucasians than African Americans. Very low birth weight infants have immature
      retinas and are susceptible to ROP. Because of differences in individual
      responses to the treatment, various genetic factors have been looked into to
      understand the etiology of ROP. Endothelial nitric oxide (eNO) serves as a
      vasodilator, relaxes smooth muscle, prevents platelet aggregation, and
      facilitates improved blood flow and vascular tonicity. Mutant eNO synthase (eNOS)
      genotypes result in reduced nitric oxide levels by decreasing enzyme activity.
      Since eNO affects vasculature and ROP is a vascular disease, the present
      investigation was aimed at studying the association of genotypes with ROP.
      METHODS: Two eNOS gene single nucleotide polymorphisms (SNPs) (T-786C, and G894T)
      were studied by microplate-Restriction Fragment Length Polymorphism Polymerase
      Chain Reaction (RFLP PCR) method. Genotypes were studied in 146 premature
      infants. RESULTS: The present data showed significant differences in the baseline
      gene frequencies between Caucasians and African Americans. ROP patients displayed
      3-fold higher frequencies of mutant -786C and 894T alleles in both ethnicities
      compared to respective controls. CONCLUSIONS: The present data suggest ethnic
      stratification of genotypes. Mutant -786C and 894T alleles are significant risk
      factors in the development of ROP, and suggest a strong association between eNOS
      polymorphisms and the disease. It is interesting to know if a larger dataset of
      ROP patients can confirm our initial findings.

PMID- 20809775
TI  - Reduced frequency of known mutations in a cohort of LHON patients from India.
AB  - BACKGROUND: Three mitochondrial mutations account for 95% of Leber's hereditary
      optic neuropathy (LHON) in the European population: G3640A, G11778A and T14484C.
      The purpose of the study was to investigate the frequency of these mitochondrial
      DNA mutations in LHON patients from a South Indian population. METHODS: LHON was
      diagnosed by inheritance pattern, ophthalmologic examination, and by exclusion of
      non-LHON forms of optic neuropathy. Ninety unrelated LHON patients and 20 at-risk
      family members (5 with LHON and 15 without LHON) underwent molecular screening
      for the mitochondrial DNA mutations G3640A, G11778A and T14484C by amplification
      refractory mutation system (ARMS) polymerase chain reaction (PCR). Positive
      results were confirmed with bi-directional sequencing. RESULTS: The G11778A
      mutation was detected in 8 of 90 (8.9%) LHON families. The T14484 mutation was
      detected in 3 of 90 (3.3%) LHON families. No instances of the G3460A mutation
      were detected. Other variants were incidentally detected by the DNA sequencing
      assay. CONCLUSIONS: Three mitochondrial mutations (G3640A, G11778A and T14484C)
      account for the vast majority of LHON cases in Europe. However, these mutations
      were detected in only 11 (12%) of 90 LHON families from Southern India in our
      study. These results suggest that a different set of LHON-causing mutations is
      present in the South Indian population than in the European population. Further
      study of subjects with LHON from India may lead to the discovery of novel disease
      causing mutations and/or genes.

PMID- 20809777
TI  - (106)Ruthenium brachytherapy for ciliary recurrence with supraciliary effusion in
      retinoblastoma.
AB  - PURPOSE: A 2-year-old boy with syndromic bilateral retinoblastoma resulting from
      a (del(13)(q12.3q14.3)) developed a recurrent tumor measuring 2.3 X 2.3 mm at the
      ora serrata 15 months following last treatment. METHODS: Ultrasound biomicroscopy
      (UBM) revealed a mass invading the ciliary body 6.6 mm in diameter associated
      with a localized supraciliary effusion. RESULTS: Complete tumor regression was
      achieved 1 month after brachytherapy with a (106)Ruthenium plaque. There was no
      recurrence at 16 months. CONCLUSION: This is the first clinical demonstration of
      supraciliary effusion in recurrent retinoblastoma. Brachytherapy appears to be
      effective in the treatment of this type of recurrence.

PMID- 20809778
TI  - Organizational behavior.

PMID- 20809779
TI  - The CO-OP twist.

PMID- 20809780
TI  - Development as the acquisition of familiarity.

PMID- 20809781
TI  - The school as a social situation.

PMID- 20809782
TI  - Comparative cognition: representations and processes in learning and memory.

PMID- 20809783
TI  - Attribution theory and research.

PMID- 20809784
TI  - Mitochondrial/lysosomal toxic cross-talk plays a key role in cisplatin
      nephrotoxicity.
AB  - Cisplatin is widely used chemotherapeutic agent for the treatment of several
      human malignancies. Dose-related nephrotoxicity is the major adverse effect of
      cisplatin. The cellular and molecular mechanisms behind the cisplatin
      nephrotoxicity have not yet been completely understood. In this study, cytotoxic
      effect of cisplatin on renal proximal tubular (RPT) cells was evaluated. Our
      results showed that cytotoxic action of cisplatin on RPT cells is mediated by
      reactive oxygen species (ROS) formation, decline of mitochondrial membrane
      potential, increase in caspase-3 activity and lysosomal membrane leakiness before
      cell lysis ensued. All of the above mentioned cisplatin-induced oxidative stress
      cytotoxicity markers were significantly (p&#x2009;<&#x2009;0.05) prevented by ROS
      scavengers, antioxidants, mitochondrial permeability transition (MPT) pore
      sealing agents, endocytosis inhibitors and adenosine triphosphate (ATP)
      generators. Our results also showed that CYP2E1 involves in cisplatin oxidative
      stress cytotoxicity mechanism and intracellular nitric oxide enhancement protects
      the RPT cells against the cisplatin-induced cytotoxicity. It seems that cisplatin
      nephrotoxicity is associated with mutual mitochondrial/lysosomal potentiation
      (cross-talk) of oxidative stress in RPT cells. This cross-talk finally results in
      release of lysosomal digestive proteases and phospholipases and mitochondrial MPT
      pore opening leading to cytochrome c release and activation of caspases cascade
      which signal apoptosis.

PMID- 20809787
TI  - Deregulated semantic cognition follows prefrontal and temporo-parietal damage:
      evidence from the impact of task constraint on nonverbal object use.
AB  - Semantic cognition, which encompasses all conceptually based behavior, is
      dependent on the successful interaction of two key components: conceptual
      representations and regulatory control. Qualitatively distinct disorders of
      semantic knowledge follow damage to the different parts of this system. Previous
      studies have shown that patients with multimodal semantic impairment following
      CVA--a condition referred to as semantic aphasia (SA)--perform poorly on a range
      of conceptual tasks due to a failure of executive control following prefrontal
      and/or temporo-parietal infarction [Jefferies, E., & Lambon Ralph, M. A. Semantic
      impairment in stroke aphasia versus semantic dementia: A case-series comparison.
      Brain, 129, 2132-2147, 2006]. Although a deficit of core semantic control would
      be expected to impair all modalities in parallel, most research exploring this
      condition has focused on tasks in the verbal domain. In a novel exploration of
      semantic control in the nonverbal domain, therefore, we assessed eight patients
      with SA on two experiments that examined object use knowledge under different
      levels of task constraint. Patients exhibited three key characteristics of
      semantic deregulation: (a) difficulty using conceptual knowledge flexibly to
      support the noncanonical uses of everyday objects; (b) poor inhibition of
      semantically related distractor items; and (c) improved object use with the
      provision of more tightly constraining task conditions following verbal and
      pictorial cues. Our findings are consistent with the notion that a neural network
      incorporating the left inferior prefrontal and temporo-parietal areas (damaged in
      SA) underpins regulation of semantic activation across both verbal and nonverbal
      modalities.

PMID- 20809788
TI  - Design and quality of ICF-compatible data items for national disability support
      services.
AB  - PURPOSE: To examine the structure, distribution and interrelationships of
      International Classification of Functioning, Disability and Health (ICF)
      compatible items in Australia's national data collection about disability support
      services. METHOD: Rasch analyses were carried out on 93,000 records relating to
      people aged 15 to 64 years, receiving disability support services in Australia in
      2003. The range of disabilities and services received was diverse. 'Support
      needs', in all nine life areas based on the ICF Activities and Participation
      domains, are recorded in the national data collection in one of the following
      three categories: 'needs no help/supervision in this life area'; 'sometimes needs
      help/supervision'; or 'always needs help/supervision or unable to do activity'.
      RESULTS: The results of the analysis demonstrate the value of the 'support needs'
      questions. The three categories of need for support were distinct and widely
      separated; the ICF domains were also found to be distinct. The results also
      showed that 'support needs' in one subset of ICF Activities and Participation
      domains could not be used to predict values in another subset. CONCLUSIONS: The
      two-dimensional question about 'support needs' offers promise as a general data
      capture tool for indicating 'extent' of disability. Caution should be exercised
      in the omission of any ICF Activities and Participation life areas for
      measurement in diverse populations.

PMID- 20809785
TI  - Nogo receptor deletion and multimodal exercise improve distinct aspects of
      recovery in cervical spinal cord injury.
AB  - We tested the ability of two plasticity-promoting approaches to enhance recovery
      in a mouse model of incomplete spinal cord injury (SCI). Genetically, we reduced
      myelin-mediated inhibition of neural plasticity through Nogo66-receptor (NgR)
      gene deletion. Behaviorally, we utilized a novel multimodal exercise training
      paradigm. Adult mice of wild-type or NgR-null genotype were subjected to partial
      lateral hemisection (LHx) at C3-C4 with the intent of producing anatomically and
      functionally mild deficits. Exercise training or control treatment proceeded for
      14 weeks. Behavioral outcomes were assessed prior to tract tracing and
      histological analysis. Genotype and training exerted differing effects on
      performance; training improved performance on a test related to the training
      regimen (task-specific benefit), whereas genotype also improved performance on
      more generalized behaviors (task-non-specific benefit). There were no significant
      histological differences across genotype or training assignment with regard to
      lesion size or axonal tract staining. Thus either NgR gene deletion or exercise
      training benefits mice with mild cervical spinal injury. In this lesion model,
      the effects of NgR deletion and training were not synergistic for the tasks
      assessed. Further work is required to optimize the interaction between
      pharmacological and physical interventions for SCI.

PMID- 20809786
TI  - Chondroitinase ABC enhances pericontusion axonal sprouting but does not confer
      robust improvements in behavioral recovery.
AB  - Traumatic brain injury (TBI) results in enduring functional deficits. Strategies
      aimed at promoting plasticity within the injured brain may aid in enhancing
      functional outcome. We have previously shown that spontaneous pericontusional
      axon sprouting occurs within 7-14 days after controlled cortical impact injury in
      the adult rat, but ultimately fails due to an increasingly growth-inhibitory
      environment. We therefore sought to determine whether acute infusion of
      chondroitinase ABC into the site of the cortical contusion, to further reduce
      pericontusional growth-inhibitory chondroitin sulfate proteoglycans (CSPGs),
      would enhance and prolong the sprouting response. We also wanted to determine if
      chondroitinase-enhanced sprouting would ameliorate the behavioral deficits in
      forelimb function that occur in this model. Acute chondroitinase infusion
      decreased intact CSPGs and significantly increased pericontusional cortical grey
      and white matter growth-associated protein 43 (GAP43)-positive axon sprouting at
      7 days post-injury. A return of intact CSPGs at later time points likely
      contributed to the absence of persistently increased levels of axon sprouting by
      14-21 days post-injury. There was no overall benefit on forelimb function during
      the time of maximal sprouting or at any subsequent times in three of four
      behavioral outcome measures. However, there was a chondroitinase-induced
      improvement in recovery from unskilled limb use deficits on the staircase
      forelimb reaching test toward sham-injured values at 28 days, which was not
      achieved by the vehicle-treated rats, indicating that there is some minor
      functional benefit of the increased sprouting induced by chondroitinase
      treatment. The current results, together with data from spinal cord injury models
      after chondroitinase intervention, suggest that a combinatorial approach with the
      addition of neurotrophins and rehabilitation would result in more robust axon
      sprouting and consequently improve behavioral outcome.

PMID- 20809789
TI  - Speech perception.
AB  - Speech perception has been studied for over a half century. During this time, one
      subfield has examined perception of phonetic information independent of its
      contribution to word recognition. Theories in this subfield include ones that are
      based on auditory properties of speech, the motor commands involved in speech
      production, and a Direct Realist approach that emphasizes the structure of the
      information reaching the perceiver. A second subfield has been less concerned
      with the acoustic-phonetic properties of speech and more concerned with how words
      are segmented and recognized. In this subfield, there has been a focus on the
      nature of communication among different levels of analysis (e.g., phonetic and
      lexical). In recent years, there has been a growing appreciation of the need to
      understand how the perceptual system dynamically changes in order to allow
      listeners to successfully process the variable input and new words that they
      constantly encounter.

PMID- 20809791
TI  - Attitudes and attitude change.
AB  - Attitudes and attitude change remain core topics of contemporary social
      psychology. This selective review emphasizes work published from 2005 to 2009. It
      addresses constructionist and stable-entity conceptualizations of attitude, the
      distinction between implicit and explicit measures of attitude, and implications
      of the foregoing for attitude change. Associative and propositional processes in
      attitude change are considered at a general level and in relation to evaluative
      conditioning. The role of bodily states and physical perceptions in attitude
      change is reviewed. This is followed by an integrative perspective on processing
      models of persuasion and the consideration of meta-cognitions in persuasion.
      Finally, effects of attitudes on information processing, social memory, and
      behavior are highlighted. Core themes cutting across the areas reviewed are
      attempts at integrative theorizing bringing together formerly disparate phenomena
      and viewpoints.

PMID- 20809790
TI  - Thirty years and counting: finding meaning in the N400 component of the event
      related brain potential (ERP).
AB  - We review the discovery, characterization, and evolving use of the N400, an event
      related brain potential response linked to meaning processing. We describe the
      elicitation of N400s by an impressive range of stimulus types--including written,
      spoken, and signed words or pseudowords; drawings, photos, and videos of faces,
      objects, and actions; sounds; and mathematical symbols--and outline the
      sensitivity of N400 amplitude (as its latency is remarkably constant) to
      linguistic and nonlinguistic manipulations. We emphasize the effectiveness of the
      N400 as a dependent variable for examining almost every aspect of language
      processing and highlight its expanding use to probe semantic memory and to
      determine how the neurocognitive system dynamically and flexibly uses bottom-up
      and top-down information to make sense of the world. We conclude with different
      theories of the N400's functional significance and offer an N400-inspired
      reconceptualization of how meaning processing might unfold.

PMID- 20809792
TI  - Mechanisms underlying rapid aldosterone effects in the kidney.
AB  - The steroid hormone aldosterone is a key regulator of electrolyte transport in
      the kidney and contributes to both homeostatic whole-body electrolyte balance and
      the development of renal and cardiovascular pathologies. Aldosterone exerts its
      action principally through the mineralocorticoid receptor (MR), which acts as a
      ligand-dependent transcription factor in target tissues. Aldosterone also
      stimulates the activation of protein kinases and secondary messenger signaling
      cascades that act independently on specific molecular targets in the cell
      membrane and also modulate the transcriptional action of aldosterone through MR.
      This review describes current knowledge regarding the mechanisms and targets of
      rapid aldosterone action in the nephron and how aldosterone integrates these
      responses into the regulation of renal physiology.

PMID- 20809795
TI  - Laboring in the vineyard of physical chemistry.
AB  - This is an account mostly of what I have seen and worked on in physical
      chemistry, from my time in graduate school six decades ago to the present. It is
      a personal story about kinetics, thermodynamics, and statistical mechanics--in
      which subjects I continue to be educated, thanks to patient instruction by my
      students and associates. When I had the invitation from Steve Leone to write this
      article I said "yes" because (a) "yes" is my default setting; (b) it was a great
      honor to have been invited to do it; and (c) I was too busy at the time to think
      about what the consequences of saying "yes" would be. I must now do my best to
      fulfill my promise.

PMID- 20809796
TI  - A 40-year journey in search of selective antiviral chemotherapy.
AB  - My search for a selective antiviral chemotherapy started more than 40 years ago
      with interferon inducers, then shifted to nucleoside analogs with the discovery
      of BVDU (brivudin), a highly selective anti-HSV-1 and anti-VZV agent, and to
      dideoxynucleoside analogs such as d4T (stavudine), anti-HIV agents. The search
      culminated in the discovery of acyclic nucleoside phosphonates (ANPs) (in
      collaboration with Antonin Holy), a key class of compounds active against HIV,
      hepatitis B virus, and DNA viruses at large; the best known of these compounds is
      tenofovir. Along the way, the principle of the non-nucleoside reverse
      transcriptase inhibitors (NNRTIs) was established. This work, initiated in
      collaboration with the late Paul A.J. Janssen, eventually led to the
      identification of rilpivirine as perhaps an "ideal" NNRTI.

PMID- 20809794
TI  - Heart valve structure and function in development and disease.
AB  - The mature heart valves are made up of highly organized extracellular matrix
      (ECM) and valve interstitial cells (VICs) surrounded by an endothelial cell
      layer. The ECM of the valves is stratified into elastin-, proteoglycan-, and
      collagen-rich layers that confer distinct biomechanical properties to the
      leaflets and supporting structures. Signaling pathways have critical functions in
      primary valvulogenesis as well as the maintenance of valve structure and function
      over time. Animal models provide powerful tools to study valve development and
      disease processes. Valve disease is a significant public health problem, and
      increasing evidence implicates aberrant developmental mechanisms underlying
      pathogenesis. Further studies are necessary to determine regulatory pathway
      interactions underlying valve pathogenesis in order to generate new avenues for
      novel therapeutics.

PMID- 20809793
TI  - Niemann-pick C1-like 1 (NPC1L1) protein in intestinal and hepatic cholesterol
      transport.
AB  - Increased blood cholesterol is an independent risk factor for atherosclerotic
      cardiovascular disease. Cholesterol homeostasis in the body is controlled mainly
      by endogenous synthesis, intestinal absorption, and hepatic excretion. Niemann
      Pick C1-Like 1 (NPC1L1) is a polytopic transmembrane protein localized at the
      apical membrane of enterocytes and the canalicular membrane of hepatocytes. It
      functions as a sterol transporter to mediate intestinal cholesterol absorption
      and counter-balances hepatobiliary cholesterol excretion. NPC1L1 is the molecular
      target of ezetimibe, a potent cholesterol absorption inhibitor that is widely
      used in treating hypercholesterolemia. Recent findings suggest that NPC1L1
      deficiency or ezetimibe treatment also prevents diet-induced hepatic steatosis
      and obesity in addition to reducing blood cholesterol. Future studies should
      focus on molecular mechanisms underlying NPC1L1-dependent cholesterol transport
      and elucidation of how a cholesterol transporter modulates the pathogenesis of
      metabolic diseases.

PMID- 20809797
TI  - microRNAs: Master regulators as potential therapeutics in cancer.
AB  - It has been demonstrated that all the known processes involved in cancer,
      including apoptosis, proliferation, survival, and metastasis, are regulated by
      small regulatory noncoding RNAs consisting of approximately 19-25 nucleotides;
      these are named microRNAs (miRNAs). Both loss and gain of miRNA function
      contribute to cancer development through the upregulation and silencing,
      respectively, of different target genes. Experimental evidence indicates that the
      use of miRNA mimics or anti-microRNAs may represent a powerful therapeutic
      strategy to interfere with key molecular pathways involved in cancer. This review
      provides insights about how micro- RNAs act as oncogenes and tumor suppressor
      genes and how these findings, along with our increasing understanding of miRNA
      regulation, can be applied to optimize recent miRNA-based technologies and make
      them suitable for clinical applications.

PMID- 20809798
TI  - Role of postmarketing surveillance in contemporary medicine.
AB  - Contemporary medicine is a large and complex system involving many participants,
      all of whom play a critical role in managing the risks intrinsic to medical
      product use. Despite the robust premarket review and approval process of the U.S.
      Food and Drug Administration (FDA), new information will inevitably be learned in
      the postmarketing period about the safety of medicines and how they are and
      should be used. For much of this information, FDA relies on public reports about
      possible adverse events. In turn, the public depends on FDA to communicate the
      most up-to-date safety information on medical products to better inform treatment
      decisions. Expanding the scope and strengthening the capabilities of the drug
      safety surveillance system are among key FDA projects designed to reduce
      avoidable injury and death from medication use. Although improving drug safety is
      our goal and obligation to the public, FDA cannot protect the public adequately
      without the active involvement of all participants in healthcare.

PMID- 20809799
TI  - The genetics of lignin biosynthesis: connecting genotype to phenotype.
AB  - The processes underlying lignification, which for many years have been the near
      exclusive purview of chemists and biochemists, have more recently been approached
      using both classical forward genetic screens and targeted reverse genetic
      approaches such as antisense suppression, RNAi, and characterization of
      insertional mutants. In this review, we provide an overview of the current
      understanding of lignin biosynthesis and structure, with emphasis on mutant and
      transgenic plants that have contributed to this knowledge. We also discuss
      ongoing work aimed at elucidating the relationship between lignin structure and
      function in vivo, as well as the phenotypic consequences arising from genetic
      manipulation of the lignin biosynthetic pathway.

PMID- 20809801
TI  - Variable tandem repeats accelerate evolution of coding and regulatory sequences.
AB  - Genotype-to-phenotype mapping commonly focuses on two major classes of mutations:
      single nucleotide polymorphisms (SNPs) and copy number variation (CNV). Here, we
      discuss an underestimated third class of genotypic variation: changes in
      microsatellite and minisatellite repeats. Such tandem repeats (TRs) are
      ubiquitous, unstable genomic elements that have historically been designated as
      nonfunctional "junk DNA" and are therefore mostly ignored in comparative
      genomics. However, as many as 10% to 20% of eukaryotic genes and promoters
      contain an unstable repeat tract. Mutations in these repeats often have
      fascinating phenotypic consequences. For example, changes in unstable repeats
      located in or near human genes can lead to neurodegenerative diseases such as
      Huntington disease. Apart from their role in disease, variable repeats also
      confer useful phenotypic variability, including cell surface variability,
      plasticity in skeletal morphology, and tuning of the circadian rhythm. As such,
      TRs combine characteristics of genetic and epigenetic changes that may facilitate
      organismal evolvability.

PMID- 20809802
TI  - Climate change and evolutionary adaptations at species' range margins.
AB  - During recent climate warming, many insect species have shifted their ranges to
      higher latitudes and altitudes. These expansions mirror those that occurred after
      the Last Glacial Maximum when species expanded from their ice age refugia.
      Postglacial range expansions have resulted in clines in genetic diversity across
      present-day distributions, with a reduction in genetic diversity observed in a
      wide range of insect taxa as one moves from the historical distribution core to
      the current range margin. Evolutionary increases in dispersal at expanding range
      boundaries are commonly observed in virtually all insects that have been studied,
      suggesting a positive feedback between range expansion and the evolution of
      traits that accelerate range expansion. The ubiquity of this phenomenon suggests
      that it is likely to be an important determinant of range changes. A better
      understanding of the extent and speed of adaptation will be crucial to the
      responses of biodiversity and ecosystems to climate change.

PMID- 20809800
TI  - Circadian control of global gene expression patterns.
AB  - An internal time-keeping mechanism has been observed in almost every organism
      studied from archaea to humans. This circadian clock provides a competitive
      advantage in fitness and survival ( 18, 30, 95, 129, 137 ). Researchers have
      uncovered the molecular composition of this internal clock by combining
      enzymology, molecular biology, genetics, and modeling approaches. However,
      understanding the mechanistic link between the clock and output responses has
      been elusive. In three model organisms, Arabidopsis thaliana, Drosophila
      melanogaster, and Mus musculus, whole-genome expression arrays have enabled
      researchers to investigate how maintaining a time-keeping mechanism connects to
      an adaptive advantage. Here, we review the impacts transcriptomics have had on
      our understanding of the clock and how this molecular clock connects with system
      level circadian responses. We explore the discoveries made possible by high
      throughput RNA assays, the network approaches used to investigate these large
      transcript datasets, and potential future directions.

PMID- 20809803
TI  - Native and exotic pests of eucalyptus: a worldwide perspective.
AB  - Eucalyptus species, native to Australia, Indonesia, the Philippines, and New
      Guinea, are the most widely planted hardwood timber species in the world. The
      trees, moved around the globe as seeds, escaped the diverse community of
      herbivores found in their native range. However, a number of herbivore species
      from the native range of eucalypts have invaded many Eucalyptus-growing regions
      in North America, Europe, Africa, Asia, and South America in the last 30 years.
      In addition, there have been shifts of native species, particularly in Africa,
      Asia, and South America, onto Eucalyptus. There are risks that these species as
      well as generalist herbivores from other parts of the world will invade Australia
      and threaten the trees in their native range. The risk to Eucalyptus plantations
      in Australia is further compounded by planting commercially important species
      outside their endemic range and shifting of local herbivore populations onto new
      host trees. Understanding the mechanisms underlying host specificity of
      Australian insects can provide insight into patterns of host range expansion of
      both native and exotic insects.

PMID- 20809804
TI  - The alfalfa leafcutting bee, Megachile rotundata: the world's most intensively
      managed solitary bee.
AB  - The alfalfa leafcutting bee (ALCB), Megachile rotundata F. (Megachildae), was
      accidentally introduced into the United States by the 1940s. Nest management of
      this Eurasian nonsocial pollinator transformed the alfalfa seed industry in North
      America, tripling seed production. The most common ALCB management practice is
      the loose cell system, in which cocooned bees are removed from nesting cavities
      for cleaning and storage. Traits of ALCBs that favored their commercialization
      include gregarious nesting; use of leaves for lining nests; ready acceptance of
      affordable, mass-produced nesting materials; alfalfa pollination efficacy; and
      emergence synchrony with alfalfa bloom. The ALCB became a commercial success
      because much of its natural history was understood, targeted research was
      pursued, and producer ingenuity was encouraged. The ALCB presents a model system
      for commercializing other solitary bees and for advancing new testable hypotheses
      in diverse biological disciplines.

PMID- 20809805
TI  - Urticating hairs in arthropods: their nature and medical significance.
AB  - The ecological phenomenon of arthropods with defensive hairs is widespread. These
      urticating hairs can be divided into three categories: true setae, which are
      detachable hairs in Lepidoptera and in New World tarantula spiders; modified
      setae, which are stiff hairs in lepidopteran larvae; and spines, which are
      complex and secretion-filled structures in lepidopteran larvae. This review
      focuses on the true setae because their high density on a large number of common
      arthropod species has great implications for human and animal health. Morphology
      and function, interactions with human tissues, epidemiology, and medical impact,
      including inflammation and allergy in relation to true setae, are addressed.
      Because data from epidemiological and other clinical studies are ambiguous with
      regard to frequencies of setae-caused allergic reactions, other mechanisms for
      setae-mediated disease are suggested. Finally, we briefly discuss current
      evidence for the adaptive and ecological significance of true setae.

PMID- 20809807
TI  - Durezol (Difluprednate Ophthalmic Emulsion 0.05%) compared with Pred Forte 1%
      ophthalmic suspension in the treatment of endogenous anterior uveitis.
AB  - PURPOSE: The aim of this study was to evaluate the efficacy and safety of
      difluprednate ophthalmic solution 0.05% (Durezol; Alcon Laboratories, Fort Worth,
      TX) compared with prednisolone acetate ophthalmic suspension 1% (Pred Forte;
      Allergan, Inc., Irvine, CA) for endogenous anterior uveitis. METHODS: In this
      phase 3, multicenter, randomized, noninferiority trial, 90 patients with
      endogenous anterior uveitis [>10 anterior chamber (AC) cells and an AC flare
      score of >=2 in at least 1 eye] received either difluprednate 4x /day (QID)
      (n=50) or prednisolone 8x/day (n=40) for 14 days, followed by a 2-week tapering
      regimen. The main outcome measure was change from baseline in AC cell grade on
      day 14. RESULTS: At day 14, mean AC cell grade improvement for difluprednate
      treated patients was similar to prednisolone-treated patients (2.1 vs. 1.9,
      respectively), proving noninferiority. At day 14, 68.8% of difluprednate patients
      had AC cell clearing (grade 0:>= 1cell) compared with 61.5% of prednisolone
      patients. In the prednisolone-treated group, 12.5% of patients were withdrawn
      because of investigator-determined lack of efficacy; no difluprednate-treated
      patients were withdrawn for this reason (P=0.01). Clinically significant
      intraocular pressure elevation occurred in 3 difluprednate-treated patients
      (6.0%) and 2 prednisolone-treated patients (5.0%). CONCLUSIONS: Difluprednate
      administered QID is at least as effective as prednisolone administered 8x/day in
      resolving the inflammation and pain associated with endogenous anterior uveitis.
      Difluprednate provides effective treatment for anterior uveitis and requires less
      frequent dosing than prednisolone acetate. CLINICAL TRIAL REGISTRATION: Trial
      NCT00501579 was registered at the National Institutes of Health Registry in July
      2007 ( http://clinicaltrials.gov/ct2/show/NCT00501579?term=sirion&rank=4 ).

PMID- 20809808
TI  - Trends and predictors of publicly subsidized chiropractic service use among
      adults age 50+.
AB  - OBJECTIVES: This article examines trends in and predictors of publicly subsidized
      chiropractic use from 1991 to 2000, a decade characterized by health care system
      reforms throughout North America. SAMPLE: The sample included adults age 50+ who
      visited a publicly subsidized chiropractor in the Canadian province of British
      Columbia during the study period. DESIGN: Administrative claims data for
      chiropractic service use were drawn from the Medical Services Plan (MSP) Master
      file in the British Columbia Linked Health Data resource. The MSP Master file
      contains claims reported for every provincially insured medical service and
      supplementary health benefit including chiropractic visits. RESULTS: Joinpoint
      regression analyses demonstrate that while annual rates of chiropractic users did
      not change over the decade, visit rates decreased during this period. Predictors
      of a greater number of chiropractic visits include increasing age, female gender,
      urban residence, low to moderate income, and use of chiropractic services earlier
      in the decade. CONCLUSIONS: The trend toward decreasing visit rates over the
      1990s both conflicts with and is consistent with findings from other North
      American chiropractic studies using similar time periods. Results indicating that
      low and moderate income and advancing age predict more frequent chiropractic
      service are novel. However, given that lower income and older individuals were
      exempted from chiropractic service limits during this period, these results
      suggest support for the responsive nature of chiropractic use to financial
      barriers.

PMID- 20809809
TI  - The effects of a 5-week therapeutic horseback riding program on gross motor
      function in a child with cerebral palsy: a case study.
AB  - PURPOSE: The purpose of this study was to determine the outcome of a short-term
      therapeutic horseback riding intervention on the gross motor function in a child
      with cerebral palsy. DESIGN: This study employed a repeated-measures design with
      a pretest, a post-test, and a post post-test conducted 5 weeks apart using the
      Gross Motor Function Measure (GMFM) as an outcome measure. The three sets of test
      scores from the GMFM were compared upon completion of the intervention.
      INTERVENTION: The subject participated in a 5-week therapeutic horseback riding
      program consisting of 1 hour of riding per week. Each riding session consisted of
      stretching, strengthening, and balance activities. The child's level of motor
      function was tested prior to the intervention, upon completion of the
      intervention, and 5 weeks postintervention. The GMFM, a criterion-referenced
      observational measure designed to measure change in the gross motor function in
      children with cerebral palsy, was chosen as the assessment tool. RESULTS: Upon
      completion of the 5-week intervention, the child was observed to have improved
      scores on the GMFM in two of the five dimensions measured and scored for a total
      of eight items. The post post-test was completed 5 weeks after the final riding
      session and the results demonstrated successful maintenance of the improved
      scores in seven of eight items. CONCLUSIONS: The result of this case study
      suggest that 5 weeks of therapeutic riding are sufficient to produce positive
      changes in the gross motor function of a child with cerebral palsy.

PMID- 20809810
TI  - Integrative medicine: enhancing quality in primary health care.
AB  - OBJECTIVES: Integrative medicine (IM) is an emerging model of health care in
      Australia. However, little is known about the contribution that IM makes to the
      quality of health care. The aim of the research was to understand the
      contribution IM can make to the quality of primary care practices from the
      perspectives of consumers and providers of IM. DESIGN: This interpretive research
      used hermeneutic phenomenology to understand meanings and significance that
      patients and practitioners attach to their experiences of IM. Various qualitative
      research techniques were used: case studies; focus groups; and key informant
      interviews. Data sets were generated from interview transcripts and field notes.
      Data analysis consisted of repeatedly reading and examining the data sets for
      what they revealed about experiences of health care and health outcomes, and
      constantly comparing these to allow themes and patterns to emerge. SETTING: The
      setting for this research was Australian IM clinics where general medical
      practitioners and CAM practitioners were co-located. RESULTS: From the
      perspective of patients and practitioners, IM: (1) provided authentically patient
      centered care; (2) filled gaps in treatment effectiveness, particularly for
      certain patient populations (those with complex, chronic health conditions, those
      seeking an alternative to pharmaceutical health care, and those seeking health
      promotion and illness prevention); and (3) enhanced the safety of primary health
      care (because IM retained a general medical practitioner as the primary contact
      practitioner and because IM used strategies to increase disclosure of treatments
      between practitioners). CONCLUSIONS: According to patients and practitioners, IM
      enhanced the quality of primary health care through its provision of health care
      that was patient-centered, effective (particularly for chronic health conditions,
      nonpharmaceutical treatments, and health promotion) and safe.

PMID- 20809811
TI  - A preliminary study of the effects of a single session of Swedish massage on
      hypothalamic-pituitary-adrenal and immune function in normal individuals.
AB  - OBJECTIVES: Massage therapy is a multi-billion dollar industry in the United
      States with 8.7% of adults receiving at least one massage within the last year;
      yet, little is known about the physiologic effects of a single session of massage
      in healthy individuals. The purpose of this study was to determine effects of a
      single session of Swedish massage on neuroendocrine and immune function. It was
      hypothesized that Swedish Massage Therapy would increase oxytocin (OT) levels,
      which would lead to a decrease in hypothalamic-pituitary-adrenal (HPA) activity
      and enhanced immune function. DESIGN: The study design was a head-to-head, single
      session comparison of Swedish Massage Therapy with a light touch control
      condition. Serial measurements were performed to determine OT, arginine
      vasopressin (AVP), adrenal corticotropin hormone (ACTH), cortisol (CORT),
      circulating phenotypic lymphocytes markers, and mitogen-stimulated cytokine
      production. SETTING: This research was conducted in an outpatient research unit
      in an academic medical center. SUBJECTS: Medically and psychiatrically healthy
      adults, 18-45 years old, participated in this study. INTERVENTION: The
      intervention tested was 45 minutes of Swedish Massage Therapy versus a light
      touch control condition, using highly specified and identical protocols. OUTCOME
      MEASURES: The standardized mean difference was calculated between Swedish Massage
      Therapy versus light touch on pre- to postintervention change in levels of OT,
      AVP, ACTH, CORT, lymphocyte markers, and cytokine levels. RESULTS: Compared to
      light touch, Swedish Massage Therapy caused a large effect size decrease in AVP,
      and a small effect size decrease in CORT, but these findings were not mediated by
      OT. Massage increased the number of circulating lymphocytes, CD 25+ lymphocytes,
      CD 56+ lymphocytes, CD4 + lymphocytes, and CD8+ lymphocytes (effect sizes from
      0.14 to 0.43). Mitogen-stimulated levels of interleukin (IL)-1beta, IL-2, IL-4,
      IL-5, IL-6, IL-10, IL-13, and IFN-gamma decreased for subjects receiving Swedish
      Massage Therapy versus light touch (effect sizes from -0.22 to -0.63). Swedish
      Massage Therapy decreased IL-4, IL-5, IL-10, and IL-13 levels relative to
      baseline measures. CONCLUSIONS: Preliminary data suggest that a single session of
      Swedish Massage Therapy produces measurable biologic effects. If replicated,
      these findings may have implications for managing inflammatory and autoimmune
      conditions.

PMID- 20809812
TI  - Iatrogenic pancreatic cyst perforation successfully managed by a minimally
      invasive combined endoscopic-laparoscopic approach.
AB  - Endoscopic treatment of walled-off pancreatic necrosis is becoming more prevalent
      in clinical practice, although perforation may complicate 5% of cases, and
      efficient management of this complication is imperative. In this report, we
      present a case of necrosis cavity perforation successfully managed by a combined
      laparoscopic-endoscopic approach, with a novel method of luminal defect closure.

PMID- 20809813
TI  - The psychology of women-selected topics.

PMID- 20809814
TI  - Expandable gastric port for natural orifice translumenal endoscopic surgery.
AB  - BACKGROUND: The risk of intraabdominal contamination is a critical consideration
      during most natural orifice translumenal endoscopic surgery (NOTES) procedures.
      OBJECTIVE: The objective of this study was to determine a safe and efficient
      pathway for the endoscope in a transgastric NOTES procedure. DESIGN AND SETTINGS:
      A pilot experimental study in live pigs was performed. METHODS: Five White
      Landrace pigs, weighing approximately 30-35 kg, underwent the placement of a
      device consisting of an expandable sheath, the distal portion of which was
      composed of a fully covered self-expanding metal stent, and an introducer made
      with an outer catheter, a pushing catheter, and an inner, guiding catheter. The
      sheath was attached to the stent by suturing it in place. The initial gastric
      opening was made by means of a needle knife papilotome with electrocoagulation,
      aimed to the anterior gastric wall. Then, it was dilated with an endoscopic 1.8
      cm balloon. The set was introduced over a Savary guidewire. After the set
      placement, the outer tube was slowly retrieved. Finally, the delivery system was
      removed from the pig, leaving the entire endoscopic port in place. RESULTS: The
      expandable gastric port was placed without difficulty in all animals. Endoscope
      insertion into the expandable gastric port was very easily performed. The
      endoscope had a wide range of movement inside the peritoneal cavity. The gastric
      port sealed the gastric wall, avoiding gross contamination of the peritoneal
      cavity and maintaining the pneumoperitoneum without excessive inflation of the
      intestine. CONCLUSIONS: Use of a gastric port can minimize contamination of the
      peritoneal cavity due to the spillage of gastric contents during a transgastric
      NOTES procedure and can also facilitate performance of the procedure.

PMID- 20809815
TI  - Counseling and student development.

PMID- 20809816
TI  - Technical feasibility of robot-sewn anastomosis in robotic surgery for gastric
      cancer.
AB  - BACKGROUND: Although several studies have reported on the feasibility of robot
      assisted gastric cancer surgery using the da Vinci surgical system,
      reconstruction techniques have depended on staplers or hand sewing through
      minilaparotomy. AIM: The aim of this study is to report on the feasibility of
      reconstruction methods using a robot-sewing technique in robotic surgery for
      treatment of gastric cancer. PATIENT AND METHODS: Between January and April 2010,
      7 patients in whom gastric adenocarcinoma was diagnosed underwent robotic surgery
      including robot-sewn anastomosis. We demonstrated the surgical techniques with
      analysis of clinicopathologic characteristics and surgical outcomes. RESULTS: All
      robotic surgeries were performed without other laparoscopic instruments. Two Roux
      en-Y reconstructions for two total gastrectomy, two Roux-en-Y reconstructions,
      and three gastroduodenostomies, for five subtotal gastrectomies, were
      successfully accomplished. Total median operation time was 205 minutes, and
      median reconstruction time was 69 minutes. One patient was readmitted for stasis
      in the remnant stomach but conservatively recovered. CONCLUSIONS: A robot-sewn
      anastomosis for reconstruction in robotic surgery for gastric cancer was feasible
      regardless of the reconstruction method.

PMID- 20809817
TI  - Laparoscopic Collis-Nissen for recurrent severe reflux in pediatric patients with
      esophageal atresia and recurrent hiatal hernia.
AB  - PURPOSE: Patients following esophageal atresia repair may often have a
      congenitally short esophagus, leading to severe reflux and failed
      fundoplications. This report evaluates the efficacy of a laparoscopic Collis
      Nissen fundoplication in this group of patients who have failed a previous
      fundoplication. METHODS: From January 2005 to February 2010, 6 patients born with
      esophageal atresia presented with recurrent gastroesophageal reflux disease
      (GERD) and hiatal hernia (H/H). Patient's ages ranged from 5 to 12 years and
      weights from 17 to 32 kg. All patients had undergone at least three previous
      fundoplications and hiatal hernia repair. Four of 5 patients had at least one
      open laparotomy for their previous repair. Patient 6 had had a previous open
      Collis gastroplasty. The procedure was performed through five ports and consisted
      of a takedown of the previous fundoplication, elongation of the esophagus using
      an endoscopic stapler, closure of the hiatus using Teflon pledgets to buttress
      the repair, and formation of the fundoplication. RESULTS: All procedures were
      completed successfully laparoscopically. Procedure times ranged from 180 to 300
      minutes. A nasogastric (NG) tube was left for an average of 3 days in 5 patients.
      Patient 6 had a delayed perforation on day 3 and required reexploration and an NG
      tube that was left for 10 days. Five of 6 patients were started on feeds on day 4
      and were discharged on day 5. Patient 6 with the perforation was discharged on
      day 14. At an average follow-up of 42 months, all patients have intact wraps and
      no recurrence of their hiatal hernia. CONCLUSIONS: A laparoscopic Collis-Nissen
      in a child with previous failed fundoplication is a complex, but efficacious,
      procedure. Elongating the esophagus in patients with esophageal atresia may
      decrease the high recurrence rate of hiatal hernia in these patients and should
      be considered if the patient fails their primary repair.

PMID- 20809818
TI  - Gasless laparoscopy-assisted versus open resection of small bowel lesions.
AB  - BACKGROUND: We had developed an innovative method of minimally invasive surgery
      using gasless laparoscopy in resection of the small bowel lesion. This study
      aimed at evaluating the feasibility and efficacy of this procedure by comparison
      with traditional open small bowel surgery. METHODS: A wedge or segmental
      resection of the small bowel for removal of the lesion was performed in 25
      patients at National Taiwan University Hospital from September 2006 to January
      2009. Thirteen patients underwent gasless laparoscopy-assisted surgery (GLAS),
      and 12 patients underwent open surgery. The perioperative characteristics and
      clinical results between the two groups were compared. RESULTS: The demographics,
      clinical data, lesion size, and operative time were comparable between the GLAS
      and open surgery groups, but the wound length and blood loss were significantly
      less in the GLAS group (P < 0.001 and P = 0.021, respectively). The time to first
      postoperative flatus and first oral intake were significantly less in the GLAS
      group (P = 0.007 and 0.036, respectively). No major complication occurred in
      either group. No tumor recurrence was found after a median follow-up period of 14
      months (range = 1-30) in the GLAS group. CONCLUSIONS: GLAS for resection of the
      small bowel may be a feasible and safe procedure for the small bowel lesions. It
      has the advantages of better cosmetic outcome, less blood loss, and earlier
      recovery of bowel movement.

PMID- 20809819
TI  - Understanding the New Health Care Reform Law: Part II.

PMID- 20809820
TI  - Health coaching to improve healthy lifestyle behaviors: an integrative review.
AB  - OBJECTIVE: Chronic diseases account for 70% of U.S. deaths. Health coaching may
      help patients adopt healthy lifestyle behaviors that prevent and control
      diseases. This integrative review analyzed health coaching studies for evidence
      of effectiveness and to identify key program features. DATA SOURCE: Multiple
      electronic databases were utilized, yielding a final sample of 15 documents.
      STUDY INCLUSION AND EXCLUSION CRITERIA: The search was limited to peer-reviewed
      research articles published between 1999 and 2008. Studies were further analyzed
      if they (1) specifically cited coaching as a program intervention, and (2)
      applied the intervention to research. DATA EXTRACTION: Articles describing
      various quantitative and qualitative methodologies were critically analyzed using
      a systematic method. DATA SYNTHESIS: Data were synthesized using a matrix format
      according to purpose, method, intervention, findings, critique, and quality
      rating. RESULTS: All 15 studies utilized nonprobability sampling, 7 (47%) with
      randomized intervention and control groups. Significant improvements in one or
      more of the behaviors of nutrition, physical activity, weight management, or
      medication adherence were identified in six (40%) of the studies. Common features
      of effective programs were goal setting (73%), motivational interviewing (27%),
      and collaboration with health care providers (20%). CONCLUSIONS: Health coaching
      studies with well-specified methodologies and more rigorous designs are needed to
      strengthen findings; however, this behavioral change intervention suggests
      promise.

PMID- 20809821
TI  - Reliability and validity of the youth asset survey: an update.
AB  - PURPOSE: Improve and expand an existing youth asset scale. DESIGN: Consisted of
      seven steps: (1) review of poorer-performing items and constructs, (2) literature
      review for relevant new asset constructs/items, (3) review of revised instrument
      by panel of experts, (4) qualitative review through focus group research, (5)
      pilot-test of instrument, (6) evaluation of the performance of the instrument in
      a longitudinal study, and (7) conduct of test-retest analysis. SUBJECTS/SETTING:
      Youth (N = 1111) recruited through canvassing of randomly selected census tracts
      and blocks. MEASURES: Youth Asset Survey (YAS). ANALYSIS: Factor analysis was
      conducted on 50% of the baseline data and repeated on the second half of the
      baseline data. Correlations were computed for the test-retest analysis. RESULTS:
      Following modifications to the YAS based upon qualitative research, the survey
      was administered to youth (mean age, 14.3 years; 53% female; 39% white, 28%
      Hispanic, 23% African-American, 9% other). Cronbach alpha = .55-.92. A majority
      (27 of 34) of alpha > or = .65. All items loaded on one construct at alpha > or =
      .40. The final results yielded 17 constructs assessed via 61 items. Spearman
      correlations and intraclass correlations ranged from .60 to .82 and .58 to .87,
      respectively. CONCLUSION: The results generally suggest that the expanded YAS is
      a reliable and valid measure of assets.

PMID- 20809822
TI  - Influence of a tobacco-free hospital campus policy on smoking status of hospital
      employees.
AB  - PURPOSE: To examine the influence of a tobacco-free hospital campus (TFHC) policy
      on employee smoking behavior. DESIGN: Questionnaires immediately prior to, 6
      months after, and 1 year after implementation of a TFHC policy. SETTING:
      University-affiliated hospital system. SUBJECTS: A cohort of smokers and recent
      quitters. MEASURES: Smoking status, quit attempts, influence of TFHC policy.
      ANALYSIS: Descriptive. RESULTS: From 2024 employees who responded to an initial
      online survey prior to implementation of a TFHC policy, 307 respondents reported
      either current smoking or quitting smoking within the past 6 months. Of these,
      210 (68%) agreed to follow-up surveys at 6 and 12 months post-policy
      implementation. At each of the three times, between 15% and 18.5% of the cohort
      reported not smoking, with at least 48% of those not smoking reporting 6 to 12
      months continuous abstinence. Sixty percent or more of those who reported quit
      attempts or not smoking indicated that the TFHC policy was influential in their
      efforts. CONCLUSIONS: A TFHC policy may lead to increased employee smoking quit
      attempts and successful cessation. Health care facilities should broaden smoking
      restrictions to include the entire workplace campus, not only to reduce exposure
      to environmental tobacco smoke, but also to increase tobacco cessation.

PMID- 20809823
TI  - Federal grants to small employers for comprehensive wellness programs: passed as
      part of health care reform.

PMID- 20809825
TI  - Development, reliability, and validity of an urban trail use survey.
AB  - PURPOSE: To evaluate the psychometric characteristics of the Research on Urban
      Trail Environments (ROUTES) Trail Use Questionnaire. DESIGN: Test-retest
      reliability was assessed by repeated measures (study 1); validity was assessed by
      comparing reported trail use to self-reported and objectively measured physical
      activity (PA) levels (study 2). SETTING: Study 1: a religious institution
      situated near a Los Angeles trail. Study 2: 1-mile buffer zones surrounding three
      urban trails (Chicago, Dallas, and Los Angeles). SUBJECTS: Thirty-four adults
      between 40 and 60 years of age (10 men and 24 women) completed the ROUTES
      questionnaire twice (study 1). Study 2 participants were 490 adults (48% female
      and 73% white), mean age 48 years. MEASURES: Trail use for recreation and
      transportation purposes, time and distance spent on trails, and characteristics
      of the trail and other trail users. PA was measured using the International
      Physical Activity Questionnaire and accelerometry. ANALYSES: Pearson correlation
      coefficients and kappa statistics were used for test-retest reliability for
      continuous and categorical variables, respectively. Generalized linear models
      were used to evaluate hypotheses on PA comparing trail users and nonusers.
      RESULTS: Test-retest statistics were acceptable (kappa = .57, r = .66). Validity
      was supported by correlations between indices of trail use with self-reported PA
      and accelerometry, and significant group differences between trail users and
      nonusers in PA levels. CONCLUSIONS: The ROUTES Trail Use Questionnaire
      demonstrated good reliability and validity.

PMID- 20809826
TI  - Informal training in staff networks to support dissemination of health promotion
      programs.
AB  - PURPOSE: To study informal skill transfer via staff networks as a complement to
      formal training among afterschool childcare providers implementing a health
      promotion program. DESIGN: Cross-sectional, sociometric network analysis.
      SETTING: Boston Young Men's Christian Association (YMCA) afterschool programs
      implementing the iPLAY program. PARTICIPANTS: All 91 staff members at 20 sites
      were eligible; 80 completed the survey (88% response rate). MEASURES: At the
      network level, network density measured system-level connectedness. At the staff
      level, the independent variable was out degree, the number of individuals to whom
      respondents noted a program-related connection. The dependent variable was skill
      gains, the number of key implementation skills gained from the network. ANALYSIS:
      We mapped the staff program-related social network. We utilized multiple linear
      regression to estimate the relationship between out degree and skill gains, and
      we adjusted for clustering of staff in sites. RESULTS: Most staff (77%) reported
      gaining at least one skill from the network, but only 2% of potential network
      connections were established. The regression model showed that out degree (i.e.,
      number of program-related contacts) was significantly associated with skill gains
      (beta = .48, p < .01) independent of other variables. CONCLUSION: Informal skill
      transfer in staff networks may be a useful complement to formal training for
      implementation of health promotion programs, but informal skill transfer was
      likely underutilized in this network. Future research employing longitudinal
      and/or multisite data should examine these findings in greater detail.

PMID- 20809827
TI  - Latino Women's Spiritual Beliefs Related to Health.
AB  - PURPOSE: This study employed qualitative research to describe the relationship
      between spirituality and overall health among a sample of Latino women. A
      framework is presented for understanding this complex relationship. DESIGN:
      Findings are presented from a qualitative analysis of six 1.5-hour focus group
      sessions. SETTING: The research was conducted among Latino women living in
      Chicago, Illinois, and Northeastern New York communities. We employed a community
      based participatory research approach in which community members were active
      participants throughout the research process. SUBJECTS: Subjects were 47 Latino
      women 31 to 81 years, all of whom were Christian and the majority (43%) of whom
      had less than a high school education. Twenty-seven percent reported having high
      school diplomas, and the same percentage reported at least some college. Of the
      women who answered the questions, one did not have health insurance, 69% had
      public health insurance, and 29% had private health insurance. MEASURES: Grounded
      theory using selective coding was employed to understand the relationship between
      spirituality and health and to develop the conceptual framework. RESULTS:
      Spirituality was expressed as a vital component of health, and the belief in a
      need for balance of physical, mental, and spiritual health was described. An
      active and a passive relationship between spirituality and health emerged, with
      active being most common. Asking God for help or faith as a coping strategy were
      subdomains of the active relationship, and God responsible for health fell under
      the passive domain. These relationship types influenced beliefs about
      participation in one's own health. CONCLUSION: The findings that emerged
      contribute to an understanding of how spirituality plays a role in health beliefs
      among Latino women, which has implications for health promotion research and
      program development for addressing health disparities.

PMID- 20809828
TI  - Weight-loss programs in convenient care clinics: a prospective cohort study.
AB  - PURPOSE: Assess whether a convenient care clinic (CCC) medical weight-loss
      program can promote weight loss. DESIGN: Prospective cohort study with follow-up
      at 10 weeks. SETTING: A CCC (Lindora Health Clinic) weight-loss program (Lean for
      Life) based in a retail pharmacy (Rite Aid Pharmacy) in Costa Mesa, California.
      SUBJECTS: The first 100 people to purchase the weight-loss program. INTERVENTION:
      A 10-week, $465 medical weight-loss program with individual counseling sessions;
      a hypocaloric diet of 900 to 1200 kcal/day (25%-30% carbohydrates, 40% protein,
      25% fat); and adjunctive pharmacologic treatment, if necessary. MEASURES: We
      collected data on age, height, weight, visits per week, medication use, comorbid
      conditions, and weight change. ANALYSIS: Data were analyzed based on length of
      enrollment and mean percent weight loss. Statistical tests used were t-test and
      Spearman rank correlation test. RESULTS: Eighty-six subjects had valid data
      entries for weight change over the 10-week period. Average age was 51.6 years;
      mean starting body mass index was 30.3. Thirty patients participated for 0 to 4
      weeks, 30 for 4 to 9 weeks, and 26 for 10 weeks. Mean percent weight changes for
      the 0 to 4, 5 to 9, and 10-week groups were -1.6, -6.0, and -8.1, respectively.
      Forty-five (45%) of the patients achieved medically significant weight loss (> or
      =5%). CONCLUSION: The study shows that a medical weight-loss program offered at a
      CCC in a retail pharmacy can produce medically significant weight loss of > or
      =5%. Further research of collaborations between the retail and medical weight
      loss industries is warranted. Study design limitations included selection bias
      and confounding variables other than the weight-loss program.

PMID- 20809829
TI  - Emotional health and weight gain: a prospective study of midlife women.
AB  - PURPOSE: Investigate the extent to which risk of weight gain is affected by
      emotional health. Also, determine the influence of age, baseline weight, physical
      activity (PA), energy intake, and changes in PA and energy intake on the
      relationship between emotional health and weight gain. DESIGN: Prospective
      cohort. SETTING: Two metropolitan areas in the Mountain West. SUBJECTS: Total of
      256 middle-aged, apparently healthy women. MEASURES: Emotional health was
      assessed using the General Well-Being Schedule. PA was measured using Actigraph
      accelerometers. Energy intake was measured using 7-day weighed food records. All
      assessments were taken at baseline and again at the follow-up approximately 2
      years later. ANALYSIS: Relative risk (RR) was calculated using incidence data.
      RESULTS: With no variables controlled, women with less than positive (LTP)
      emotional health had 59% greater risk of weight gain (> or =2 kg) than women with
      positive emotional health (RR, 1.59; 95% confidence intervals [CI], 1.04-2.44).
      After adjustments for each potential confounder individually, risk of weight gain
      did not change significantly. However, adjusting for all of the potential
      confounders simultaneously weakened the risk of weight gain (RR, 1.43; 95% CI,
      .93-2.21). Risk of weight gain (> or =2 kg) was no greater in depressed women
      compared with their counterparts. CONCLUSION: Middle-aged women with LTP
      emotional health are at significantly increased risk of weight gain over time
      compared with women with positive emotional health.

PMID- 20809830
TI  - Different strategies contribute to community physical activity program
      participation in rural versus metropolitan settings.
AB  - PURPOSE: Determine if recruitment methods are differentially related to the reach
      of a physical activity program in metro/urban vs. rural settings. DESIGN: Cross
      sectional survey. SETTING: Kansas counties. SUBJECTS: Ninety-four Cooperative
      Extension agents responsible for 102 counties. MEASURES: Promotional score, task
      force activity, and years of program delivery were assessed using a self-report
      survey. Reach was assessed for each county by dividing the number of participants
      by intended population using census data. ANALYSIS: Rural/urban comparisons on
      reach were completed using a Mann-Whitney test. Multiple linear regression models
      were used to determine the relationship between independent variables and
      participation rate by setting type. RESULTS: Metro/urban counties had lower mean
      participation rates than rural counties (z = -4.5; p < .001). In metro/urban
      counties, the regression on participation rate was significant (R(2) = .19; F =
      4.09; p = .011), but only promotional score significantly contributed to the
      model (p = .003). In rural counties, the regression was also significant (R(2) =
      .34; F = 6.64; p = .001), with task force activity and years of delivery making
      significant contributions (p = .001 and p = .017, respectively). CONCLUSION:
      Interpersonal methods may be more effective in recruiting physical activity
      program participants in rural settings, whereas using a greater variety of
      promotional methods may be more effective in metro/urban settings.

PMID- 20809831
TI  - Route preferences among adults in the near market for bicycling: findings of the
      cycling in cities study.
AB  - PURPOSE: To provide evidence about the types of transportation infrastructure
      that support bicycling. DESIGN: Population-based survey with pictures to depict
      16 route types. SETTING: Metro Vancouver, Canada. SUBJECTS: 1402 adult current
      and potential cyclists, i.e., the "near market" for cycling (representing 31% of
      the population). MEASURES: Preference scores for each infrastructure type (scale
      from -1, very unlikely to use, to +1, very likely to use); current frequency of
      use of each infrastructure type (mean number of times/y). ANALYSES: Descriptive
      statistics across demographic segments; multiple linear regression. RESULTS: Most
      respondents were likely or very likely to choose to cycle on the following broad
      route categories: off-street paths (71%-85% of respondents); physically separated
      routes next to major roads (71%); and residential routes (48%-65%). Rural roads
      (21%-49%) and routes on major streets (16%-52%) were least likely to be chosen.
      Within the broad categories, routes with traffic calming, bike lanes, paved
      surfaces, and no on-street parking were preferred, resulting in increases in
      likelihood of choosing the route from 12% to 37%. Findings indicate a marked
      disparity between preferred cycling infrastructure and the route types that were
      currently available and commonly used. CONCLUSION: This study provides evidence
      for urban planners about bicycling infrastructure designs that could lead to an
      increase in active transportation.

PMID- 20809832
TI  - The worksite supportive environments for active living survey: development and
      psychometric properties.
AB  - PURPOSE: The purpose of this study was to develop a self-report instrument to
      measure perceived physical and social environmental factors in the worksite
      setting that are shown to influence physical activity. DESIGN: Initial items were
      generated from a review of the literature and were sent out for peer and expert
      panel review. A revised questionnaire was sent to 1250 participants to determine
      and test the emerging factor structure. SETTING: The instrument was tested at two
      worksites in the mid-South. PARTICIPANTS: Participants consisted of a random
      sample of regular full-time employees at the two worksites. MEASURES: Principal
      axis factoring with a varimax rotation was used to explore the data in the first
      group of participants. Confirmatory factor analysis was used to test the fit of
      the final model in the second group of participants. Measures used included the
      comparative fit index, parsimony goodness of fit index, root mean square error of
      approximation, and the root mean square residual. RESULTS: The final analysis
      showed an adequate fit of the data to the hypothesized factor structure (n =
      683). The instrument showed good internal consistency, temporal stability,
      construct reliability, and discriminant validity. CONCLUSION: The Worksite
      Supportive Environments for Active Living Survey is a reliable and valid tool for
      investigating perception of the worksite environment related to physical
      activity.

PMID- 20809836
TI  - Actively motile larval forms in fluid aspirated from lung. Hydatid cyst of the
      lung.

PMID- 20809835
TI  - Epidemiology and antimicrobial resistance of Streptococcus pneumoniae in France
      in 2007: data from the pneumococcus surveillance network.
AB  - Antimicrobial resistance of Streptococcus pneumoniae in France is closely
      monitored by the pneumococcus surveillance network, founded in 1995, which
      collects data from regional observatories (Observatoire Regionaux du Pneumocoque
      [ORP]). In 2007, 23 ORPs analyzed the antibiotic susceptibility of 5,302 isolates
      of S. pneumoniae recovered in France from cerebrospinal fluid, blood, middle ear
      fluid, and pleural fluid, as well as from adult respiratory samples. The study
      showed that 38.2% of the strains were nonsusceptible to penicillin, 19.3%
      nonsusceptible to amoxicillin, and 10.5% nonsusceptible to cefotaxime. The
      percentage of pneumococcus nonsusceptible to penicillin varied according to both
      the sample and the age of the patient (child/adult): blood (27.8%/32.5%),
      cerebrospinal fluid (33.7%/34.6%), middle ear fluid (60.2%/27.5%), and pleural
      fluid (50.0%/31.0%). Between 2003 and 2007, the frequency of penicillin
      resistance in invasive pneumococcal disease gradually decreased from 46.4% to
      29.0% in children and from 43.8% to 32.7% in adults. This decrease coincided with
      the introduction of a seven-valent pneumococcal conjugate vaccine into
      immunization programs and with a general reduction in levels of antibiotic
      consumption in France.

PMID- 20809838
TI  - Tigecycline and bacteremia--the dangers of post hoc analysis of pooled data.

PMID- 20809839
TI  - The 104 day report: a successful intervention of improving patient retention.

PMID- 20809841
TI  - Q fever, free amoeba, and air conditioning.

PMID- 20809842
TI  - Oral voriconazole dose in children: one size does not fit all.

PMID- 20809843
TI  - Risk of fatal adverse events after H1N1 influenza vaccine: limitations of passive
      surveillance data.

PMID- 20809846
TI  - Informal network of communication tools played an important role in sharing
      safety information on H1N1 influenza vaccine.

PMID- 20809850
TI  - Deep-brain stimulation for Parkinson's disease.

PMID- 20809852
TI  - Oral phosphate binders in patients with kidney failure.

PMID- 20809851
TI  - Variants of DENND1B associated with asthma in children.

PMID- 20809853
TI  - Specialist practices as medical homes.

PMID- 20809856
TI  - The American Medical Women's Association celebrates 95 years.

PMID- 20809855
TI  - Frontostriatal maturation predicts cognitive control failure to appetitive cues
      in adolescents.
AB  - Adolescent risk-taking is a public health issue that increases the odds of poor
      lifetime outcomes. One factor thought to influence adolescents' propensity for
      risk-taking is an enhanced sensitivity to appetitive cues, relative to an
      immature capacity to exert sufficient cognitive control. We tested this
      hypothesis by characterizing interactions among ventral striatal, dorsal
      striatal, and prefrontal cortical regions with varying appetitive load using fMRI
      scanning. Child, teen, and adult participants performed a go/no-go task with
      appetitive (happy faces) and neutral cues (calm faces). Impulse control to
      neutral cues showed linear improvement with age, whereas teens showed a nonlinear
      reduction in impulse control to appetitive cues. This performance decrement in
      teens was paralleled by enhanced activity in the ventral striatum. Prefrontal
      cortical recruitment correlated with overall accuracy and showed a linear
      response with age for no-go versus go trials. Connectivity analyses identified a
      ventral frontostriatal circuit including the inferior frontal gyrus and dorsal
      striatum during no-go versus go trials. Examining recruitment developmentally
      showed that teens had greater between-subject ventral-dorsal striatal
      coactivation relative to children and adults for happy no-go versus go trials.
      These findings implicate exaggerated ventral striatal representation of
      appetitive cues in adolescents relative to an intermediary cognitive control
      response. Connectivity and coactivity data suggest these systems communicate at
      the level of the dorsal striatum differentially across development. Biased
      responding in this system is one possible mechanism underlying heightened risk
      taking during adolescence.

PMID- 20809857
TI  - Occupational exposures and adverse pregnancy outcomes among nurses: a systematic
      review and meta-analysis.
AB  - BACKGROUND: The nursing profession has been associated with several adverse
      pregnancy outcomes. However, the associations between occupational exposures and
      adverse pregnancy outcomes among this group have not been systematically
      examined. This review collates all epidemiological evidence to examine the
      strength of associations and consistency among eligible studies. METHODS: A
      computer search of EMBASE and PubMed from 1966 through August 2009 was performed,
      followed by a search of reference lists of relevant studies and narrative reviews
      RESULTS: Fourteen studies explored the relation between anesthetic gases and
      spontaneous abortion, 8 the relation between anesthetic gases and congenital
      malformations, 7 the relation between chemotherapy agents and congenital
      malformations, and 4 the relation between shift work and spontaneous abortion. In
      the random-effects models the summary odds ratio (OR) was moderately elevated for
      all the relations: OR = 1.27, 95% confidence interval (CI) 0.99-1.63 for
      anesthetic gases and spontaneous abortion. The summary OR was between 1.05 and
      1.09 in high-quality studies, registry-based studies, and cohort studies: OR =
      1.33, 95% CI 1.09-1.68 for anesthetic gases and congenital malformation. The
      summary OR was between 0.97 and 1.22 for high-quality studies, registry-based
      studies, and cohort studies: OR = 1.35; 95% CI 0.91-2.01 for chemotherapy agent
      and spontaneous abortion. The summary OR was between 1.34 and 1.69 for high
      quality studies, registry-based studies, and cohort studies: OR = 1.44, 95% CI
      1.06-1.95 for shift work and spontaneous abortion. CONCLUSIONS: Nurses were found
      to be at increased risk of adverse pregnancy outcomes, but the strength of
      association was weaker in the well-designed studies. The significance of the
      findings is limited by the number and heterogeneity of the studies.

PMID- 20809858
TI  - A survey of United States periodontists' knowledge, attitudes, and behaviors
      related to tobacco-cessation interventions.
AB  - BACKGROUND: Because of the clear causal relationship between smoking and
      periodontal disease, and the negative effect of smoking on wound healing, it is
      of great importance to evaluate the tobacco-cessation interventions provided by
      periodontal practices. The use of tobacco-cessation interventions in clinical
      practice can be measured by whether the practitioner uses any of the "5 A's"
      defined by the 2008 United States Public Health Services Clinical Practice
      Guideline. METHODS: Surveys were mailed to 1,000 active members of the American
      Academy of Periodontology. The surveys assessed the periodontists' demographic
      information, educational and professional background, knowledge and attitudes
      about tobacco cessation, and use of interventions in the daily practice of
      periodontics. RESULTS: Data were collected from 231 periodontists via a self
      administered survey. Most (92%) believed that tobacco cessation is a
      responsibility of the dental profession. A pattern of declining levels of
      involvement was seen as the providers moved through the suggested "5 A's" for
      promoting tobacco cessation. Providers with formal tobacco-cessation training
      were more likely to perform interventions. The primary perceived barriers to
      providing tobacco-cessation interventions were low patient acceptance of
      treatment, lack of time, and lack of training. CONCLUSION: The findings of this
      study indicate that periodontists believe that tobacco-cessation interventions
      are a responsibility of the dental profession; however, because of several
      perceived barriers, reported rates of comprehensive tobacco interventions in
      periodontal practices are low.

PMID- 20809859
TI  - Clinical outcomes after treatment of non-contained intrabony defects with enamel
      matrix derivative or guided tissue regeneration: a 12-month randomized controlled
      clinical trial.
AB  - BACKGROUND: The purpose of this study is to compare the healing of deep, non
      contained intrabony defects (i.e., with a >=80% 1-wall component and a residual 2
      to 3-wall component in the most apical part) treated with either an enamel
      matrix derivative (EMD) or guided tissue regeneration (GTR) after 12 months.
      METHODS: In this randomized, controlled clinical trial, 40 subjects with 40
      defects affecting single-rooted teeth were treated. The defects were treated with
      EMD alone or with a non-resorbable titanium-reinforced membrane. No grafting
      materials were used. At baseline and after 12 months, clinical parameters
      including probing depths (PDs) and clinical attachment levels (CAL) were
      recorded. The difference in CAL gain was the primary outcome. RESULTS: At
      baseline, the intrabony component of the defects amounted to 8.5 +/- 2.2 mm at
      EMD-treated sites and 8.6 +/- 1.7 mm at GTR-treated sites (P = 0.47). The mean
      CAL gain at sites treated with GTR was significantly greater (P <0.001) than that
      at sites treated with EMD (4.1 +/- 1.4 mm versus 2.4 +/- 2.2 mm, respectively).
      GTR therapy, compared to EMD application alone, significantly (P = 0.01)
      increased the probability of CAL gain >=4 mm (79.2% versus 11.3%, respectively)
      and significantly (P = 0.01) decreased the probability of residual PDs >=6 mm (3%
      versus 79.3%, respectively). CONCLUSION: Although the outcomes of open-flap
      debridement alone were not investigated, the application of EMD alone appeared to
      yield less PD reduction and CAL gain compared to GTR therapy in the treatment of
      deep, non-contained intrabony defects.

PMID- 20809860
TI  - Serum lipoprotein-associated phospholipase A2 and C-reactive protein levels in
      association with periodontal disease and hyperlipidemia.
AB  - BACKGROUND: The aim of this study is to evaluate the levels of serum lipoprotein
      associated phospholipase A(2) (Lp-PLA(2)) and high-sensitivity C-reactive protein
      (hsCRP) in association with periodontal disease and hyperlipidemia. METHODS: A
      total of 123 subjects with hyperlipidemia and 68 systemically healthy controls
      were included in the study. Subjects with hyperlipidemia were divided into two
      groups: the suggested-diet (HD) and prescribed-statin (HS) groups and then into
      three subgroups: the healthy (HDh and HSh), gingivitis (HDg and HSg), and
      periodontitis (HDp and HSp) groups. Periodontal parameters were recorded and
      included the plaque index, gingival index (GI), probing depth (PD), clinical
      attachment level (CAL), and percentage of sites with bleeding on probing (BOP).
      Fasting venous blood samples were obtained, and serum lipid, Lp-PLA(2), and hsCRP
      levels were evaluated. RESULTS: Median values for the GI, PD, BOP(%), and CAL in
      the HSg group were statistically significantly higher than those in the HDg and
      systemically healthy with gingivitis (Cg) groups. The HSp group had higher
      percentages of BOP compared to those of the chronic periodontitis and HDp groups.
      The HDg group had higher serum Lp-PLA(2) and hsCRP levels compared to those of
      the Cg and HSg groups. The ratio of total cholesterol to high-density lipoprotein
      cholesterol (TC/HDL) was significantly associated with the GI, PD, and BOP(%) in
      both groups with hyperlipidemia. Serum Lp-PLA(2) and hsCRP levels were
      significantly correlated with TC/HDL, the GI, PD, and BOP(%) in the HD group.
      CONCLUSIONS: Serum Lp-PLA(2) and hsCRP levels may play an important role in the
      association between periodontal disease and hyperlipidemia, and the control of
      these mediators may affect the inflammatory control of patients with
      hyperlipidemia and periodontal disease.

PMID- 20809861
TI  - Vitamin D status and periodontal disease among pregnant women.
AB  - BACKGROUND: Maternal periodontal disease is found in < or = 40% of pregnant women
      and is associated with adverse pregnancy outcomes. Vitamin D deficiency may play
      a role in periodontal disease and tooth loss, and insufficient vitamin D status
      is common among pregnant women. The objective of this study is to examine the
      relationship between maternal vitamin D status and periodontal disease. METHODS:
      A case-control study was conducted. Cases were defined as pregnant women with
      clinical moderate to severe periodontal disease; controls were pregnant women who
      were periodontally healthy. Maternal data were chart abstracted and serum was
      collected between 14 and 26 weeks of gestation. Serum 25-hydroxyvitamin D
      (25[OH]D) levels were measured using liquid chromatography-tandem mass
      spectrometry. Median serum 25(OH)D levels and prevalence of vitamin D
      insufficiency (defined as <75 nmol/l) were compared between cases and controls.
      The odds ratio and 95% confidence interval for moderate to severe periodontal
      disease among women with vitamin D insufficiency was calculated using
      multivariable logistic regression, adjusting for maternal race, season of blood
      draw, and other potential confounders. RESULTS: A total of 117 cases were
      compared to 118 controls. Cases had lower median 25(OH)D levels than controls (59
      versus 100 nmol/l; P <0.001) and were more likely to have vitamin D insufficiency
      (65% versus 29%; P <0.001). The adjusted odds ratio (95% confidence interval) for
      moderate to severe periodontal disease among women with vitamin D insufficiency
      was 2.1 (0.99 to 4.5). CONCLUSIONS: Vitamin D insufficiency (serum 25[OH]D <75
      nmol/l) is associated with maternal periodontal disease during pregnancy. Vitamin
      D supplementation represents a potential therapeutic strategy to improve maternal
      oral health.

PMID- 20809862
TI  - Aggressive and chronic periodontitis correlate with distinct cellular sources of
      key immunoregulatory cytokines.
AB  - BACKGROUND: Chronic periodontitis (CP) and aggressive periodontitis (AP) are
      inflammatory diseases and the main cause of dental loss in adults. We aimed to
      investigate the expression of adhesion molecules and the source of
      proinflammatory and anti-inflammatory cytokines in circulating mononuclear cells
      from patients with CP and AP. METHODS: Peripheral blood mononuclear cells from
      healthy controls and CP or AP patients were collected. The expression of the cell
      adhesion molecules CD11a and CD11b, and the cellular sources of interleukin (IL)
      4, IL-10, IL-12, interferon-gamma, and tumor necrosis factor-alpha by distinct
      subpopulations of circulating leukocytes were determined using flow cytometry.
      RESULTS: The expression of CD11a, but not CD11b, was significantly higher within
      the CD4(+) and CD8(+) T cells in CP and AP than in healthy controls. The
      frequencies of tumor necrosis factor-alpha-expressing CD4(+) T cells and CD14(+)
      cells were higher in AP and CP, compared to healthy controls, respectively.
      Moreover, the frequency of IL-10 expressing CD14(+) cells was higher in CP, but
      not AP, compared to healthy controls CD4(+) T cells committed to IL-4 production
      was higher in CP than in healthy controls. CONCLUSION: These results suggest the
      participation of CD11a in the pathogenesis of periodontal lesions and show
      distinct cellular sources of immunoregulatory cytokines in AP versus CP.

PMID- 20809863
TI  - Biomechanical evaluation of subcrestal placement of dental implants: in vitro and
      numerical analyses.
AB  - BACKGROUND: This study investigates the effect of depth of insertion in
      subcrestal cortical bone (SB) and thickness of connected cortical bone (CB) for a
      subcrestal implant placement on bone stress and strain using statistical analyses
      combined with experimental strain-gauge tests and numerical finite element (FE)
      simulations. METHODS: Three experimental, artificial jawbone models and 72 FE
      models were prepared for evaluation of bone strain and stress around various
      equicrestal and subcrestal implants. For in vitro tests, rosette strain gauges
      were used with a data acquisition system to measure bone strain on the bucco
      lingual side. The maximum von Mises stresses in the bone were statistically
      analyzed by analysis of variance for FE models. RESULTS: The experimental bone
      strains reduced significantly (22% to 49%) as the thickness of CB increased. FE
      analyses indicated that the suggested CB thickness for efficiently minimizing
      bone stress was 0.5 to 2.5 mm. The results for the depth of SB were not absolute
      because obvious stress reductions only presented at a certain range of depth (0.6
      to 1.2 mm). CONCLUSION: Within the limitations of this study, increasing the
      thickness of CB and maintaining the depth of SB within a limited range can
      provide the benefit of decreasing the stress and strain in surrounding bone for
      subcrestally placed implants.

PMID- 20809864
TI  - Risk assessment before extraction for immediate implant placement in the
      posterior mandible: a computerized tomographic scan study.
AB  - BACKGROUND: Controversy exists in treatment planning relative to the attempt of
      saving a tooth with unfavorable prognosis or extracting it and placing an
      immediate or delayed implant. Preextraction radiographic assessments of teeth are
      traditionally performed using two-dimensional periapical and panoramic
      radiographs. These can reveal bone loss around a tooth, but have limited use in
      assessing implant risk before tooth extraction. Three-dimensional radiographs or
      cone-beam (CB) or computerized tomographic (CT) scans are often taken after tooth
      extraction and socket healing to assess the healed ridge as a potential implant
      site. However, when treatment planning for an immediate implant in the posterior
      mandible, a CT scan taken before tooth extraction can be of value in assessing
      the available bone and anatomy of the area. This allows the clinician and patient
      to consider alternative options, such as treating and maintaining the tooth or
      using a delayed implant protocol, when the site presents a high risk for
      immediate implant placement (IIP). The purpose of the present study is to assess
      the prevalence of sites associated with the mandibular second premolar,
      mandibular first molar, and mandibular second molar teeth that present high risk
      for IIP using a preextraction CT scan to assess the available apical bone and the
      anatomy of the posterior mandible in the area of the anticipated extraction site.
      METHODS: One hundred consecutive CT scans were obtained and screened from the New
      York University College of Dentistry, Office of Quality Assurance-Approved
      Implant Dentistry Database. Forty-one of these CT scans were further assessed
      because they included the presence of >=2 of the following tooth types:
      mandibular second premolars, mandibular first molars, and mandibular second
      molars. Measurements were obtained on the axial sections of the selected teeth to
      evaluate the amount of bone available apical to the root apices to determine the
      frequency of sites where an IIP protocol presented a high risk for inferior
      alveolar nerve injury or lingual plate perforation. RESULTS: Of the 135 teeth
      assessed from 41 CT scans, 65% of the mandibular second premolars, 53% of the
      mandibular first molars, and 73% of mandibular second molars had <6 mm of bone
      available for IIP, presenting high risk for inferior alveolar nerve injury. Of
      the sites in which the inferior alveolar canal did not limit available bone for
      IIP, 7% of the second premolars, 9% of the first molars, and 31% of the second
      molars presented high risk for lingual plate perforation. CONCLUSIONS:
      Preextraction CT scans may present a useful diagnostic aid to assess the risk of
      inferior alveolar nerve injury and lingual plate perforation for IIP in the
      posterior mandible. This information may be used for assessing risk when deciding
      whether to retain a questionable tooth or replace it with an implant with either
      an IIP or delayed protocol.

PMID- 20809865
TI  - New York state ear, nose, and throat specialists' views on pre-sinus lift
      referral.
AB  - BACKGROUND: Dental implant surgery in the posterior maxilla often involves the
      maxillary sinuses. Sinus surgery for dental implants is highly successful, but
      the preoperative risk is difficult to assess because a routine preoperative
      evaluation does not include an intranasal examination by an otolaryngologist. The
      purpose of the present study is to obtain the opinions of ear, nose, and throat
      (ENT) specialists located within New York state in an effort to establish a
      referral protocol before performing a maxillary sinus elevation. This study
      assesses the need to consult an ENT specialist for evaluation and treatment
      recommendations in the pretreatment workup. METHODS: A questionnaire and a
      stamped, return envelope with an identification number was mailed to 302
      physicians who maintained a current ENT-specialty practice or practiced that
      specialty in a hospital or clinic setting in New York state. The requirement
      criteria included a valid address and specialty designation. Up to two follow-up
      phone calls were made, and another questionnaire was mailed 30 days after the
      initial mailing. The questionnaire included eight computerized tomography
      (CT)?scan images that represented different sinus configurations. Answers to the
      five questions were statistically evaluated and analyzed. A total of 63
      recipients returned the questionnaire and were included in the study. RESULTS: A
      majority of 58.7% (95% confidence interval: 46.9% to 71.1%) of respondents
      recommended that a maxillary sinus CT scan should be routinely prescribed before
      a sinus-lift surgery. Patient symptoms that ENT specialists suggested indicated
      referral included nose complications/problems (40.1%) and sinus issues (23.6%).
      Of the eight CT-scan images, referral suggestions were >50% for the following: an
      occluded sinus with septum, inflammation at the base of the sinus only, a sinus
      with a generalized thickened membrane, an oroantral fistula, a thickened sinus
      membrane in association with teeth that had endodontic and/or periodontic
      involvement, and a nearly completely occluded sinus that was missing palatal
      bone. For patients with seasonal allergies, ENT specialists suggested delaying
      surgery (20.6%) or controlling symptoms before surgery (41.3%). Concerns included
      a past history of a sinus surgery (87.3%), chronic sinusitis (85.7%), presence of
      ostium stenosis (68.3%), nasal or sinus obstruction (82.5%), and oroantral
      fistulation (74.6%). CONCLUSIONS: Within the limits of the study, an attempt is
      made to develop a preoperative protocol, and 63 responses from ENT specialists
      suggested that the majority (58.7%) would recommend a maxillary CT scan before a
      sinus-lift surgery. Their greatest concerns were a prior sinus surgery, severe
      sinus inflammation, nasal/sinus obstruction, and oroantral fistulation.

PMID- 20809866
TI  - One-year effects of vitamin D and calcium supplementation on chronic
      periodontitis.
AB  - BACKGROUND: A previous study reported by this group found that patients in
      periodontal maintenance programs taking vitamin D and calcium supplementation had
      a trend for better periodontal health compared to patients not taking
      supplementation. The objective of the present study is to determine, for the same
      cohort of subjects, whether such differences persist over a 1-year period.
      METHODS: Fifty-one patients enrolled in maintenance programs from two dental
      clinics were recruited. Of these, 23 were taking vitamin D (>=400 IU/day) and
      calcium (>=1,000 mg/day) supplementation, and 28 were not. All subjects had at
      least two interproximal sites with >=3 mm clinical attachment loss. For
      mandibular-posterior teeth, gingival index, plaque index, probing depth,
      attachment loss, bleeding on probing, calculus index, and furcation involvement
      were evaluated. Photostimulable-phosphor, posterior bitewing radiographs were
      taken to assess alveolar bone. Daily vitamin D and calcium intakes were estimated
      by nutritional analysis. Data were collected at baseline, 6 months, and 12
      months. RESULTS: Total daily calcium and vitamin D intakes were 1,769 mg (95%
      confidence interval, 1,606 to 1,933) and 1,049 IU (781 to 1,317) in the taker
      group, and 642 mg (505 to 779) and 156 IU (117 to 195) in the non-taker group,
      respectively (P <0.001 for both). Clinical parameters of periodontal health
      improved with time in both groups (P <0.001). When clinical measures were
      considered collectively, the differences between supplement takers and non-takers
      had the following P values: baseline (P = 0.061); 6 months (P = 0.049); and 12
      months (P = 0.114). After adjusting for covariates, the P values for the effect
      of supplementation were as follows: baseline (P = 0.028); 6 months (P = 0.034);
      and 12 months (P = 0.058). CONCLUSIONS: Calcium and vitamin D supplementation
      (<=1,000 IU/day) had a modest positive effect on periodontal health, and
      consistent dental care improved clinical parameters of periodontal disease
      regardless of such supplements. Our findings support the possibility that vitamin
      D may positively impact periodontal health and confirm the need for randomized
      clinical trials on the effects of vitamin D on periodontitis.

PMID- 20809867
TI  - Optic neuritis associated with adalimumab in the treatment of uveitis.
AB  - BACKGROUND: Tumor necrosis factor (TNF) inhibitors such as adalimumab are
      increasingly used in the treatment of ocular inflammatory disease refractory to
      standard therapies. There is evidence that TNF inhibitors are associated with
      demyelinating neurologic events. OBJECTIVE: The authors report a case of optic
      neuritis and multiple sclerosis developing in association with the use of
      adalimumab for the treatment of bilateral chronic granulomatous iridocyclitis and
      multifocal choroiditis. They also review the available literature on cases of
      optic neuritis occurring in the setting of TNF inhibition. RESULTS: The authors
      identified 21 cases of optic neuritis associated with TNF inhibition; 36% of
      cases with available MRI results had evidence of other demyelinating lesions in
      the CNS. CONCLUSIONS: The strong association between TNF inhibitors and CNS
      demyelination may represent an adverse effect of these drugs. Ophthalmologists
      should recognize the relationship between TNF inhibitors and demyelinating
      disease, as it can present initially with visual symptoms.

PMID- 20809869
TI  - Varespladib methyl in cardiovascular disease.
AB  - IMPORTANCE OF THE FIELD: The high risk of recurrent cardiovascular events amongst
      patients with cardiovascular disease receiving evidence-based therapies has
      prompted investigations into complimentary treatments that may reduce residual
      risk. Analyses of clinical trials in statin-treated patients demonstrate that
      elevated lipid levels and an activated systemic inflammatory state are associated
      with a higher risk of recurrent cardiovascular events. AREAS COVERED IN THIS
      REVIEW: This article reviews evidence supporting the causal role for secretory
      phospholipase A(2) (sPLA(2)) in experimental atherosclerosis, the involvement of
      various sPLA(2) isozymes as mediators of pro-atherogenic lipoprotein remodeling
      and participants in vascular and systemic inflammatory responses, and the
      evidence that sPLA(2) inhibition reduces atherosclerosis in experimental models
      and biomarkers associated with cardiovascular events in coronary heart disease
      (CHD) patients. WHAT THE READER WILL GAIN: The experimental basis for sPLA(2)
      inhibition with varespladib methyl as a potential candidate for lowering
      recurrent cardiovascular events particularly in acute coronary syndrome patients
      is discussed. TAKE HOME MESSAGE: Varespladib methyl therapy reduces atherogenic
      lipoprotein concentrations and systemic inflammatory markers in CHD patients. The
      future role of varespladib methyl in CHD patients awaits the results of ongoing
      clinical trials.

PMID- 20809870
TI  - Asimadoline in the treatment of irritable bowel syndrome.
AB  - IMPORTANCE OF THE FIELD: Irritable bowel syndrome (IBS) represents one of the
      most common gastrointestinal disorders, with the diarrhea-predominant form (D
      IBS) representing an area of high unmet medical need. One difficulty in
      identifying suitable treatments for IBS is that although there are animal models
      for the components of IBS, it is not clear whether animals are afflicted by the
      disease. In a recently completed Phase II study, the kappa-opioid agonist,
      asimadoline, was shown to be efficacious in a prospectively defined subgroup of D
      IBS patients. This study confirmed a good safety profile for asimadoline. AREAS
      COVERED IN THIS REVIEW: The chemistry, pharmacology, pharmacokinetics,
      pharmacodynamics and clinical safety and efficacy of asimadoline in relationship
      to IBS is reviewed. Papers were searched over the past 20 years using the PubMed
      database and key words 'asimadoline', 'kappa-opioid agonist' and 'irritable bowel
      syndrome'. Abstracts were reviewed and appropriate full papers were then
      evaluated. WHAT THE READER WILL GAIN: The reader will gain an appreciation of
      kappa-opioid agonists as IBS treatments. TAKE HOME MESSAGE: In a prospectively
      defined, clinically relevant patient subgroup, asimadoline shows efficacy in the
      treatment of D-IBS.

PMID- 20809871
TI  - Is there an increase of postpartum hemorrhage, and is severe hemorrhage
      associated with more frequent use of obstetric interventions?
AB  - OBJECTIVE: To analyze changes in postpartum hemorrhage over a 10-year period from
      1998 to 2007, and to explore factors associated with severe hemorrhage. DESIGN:
      Retrospective cohort study, prospectively collected information. SETTING:
      Stavanger University Hospital, a secondary referral center, Norway. POPULATION:
      An unselected population of 41,365 women giving birth at the hospital. METHODS:
      We analyzed changes over time in mean postpartum hemorrhage, severe postpartum
      hemorrhage and associated factors. Estimated blood loss >1,000 ml was defined as
      severe hemorrhage. Data were collected from the hospital's database. MAIN OUTCOME
      MEASURES: Severe postpartum hemorrhage and obstetric interventions. RESULTS: We
      observed an increase in severe hemorrhage during the study period. After cesarean
      sections, the risk of severe hemorrhage was twice the risk of severe hemorrhage
      after vaginal deliveries (5.9%; 95% CI 5.3-6.6 vs. 2.8%; 95% CI 2.6-2.9). The
      most important factors associated with severe hemorrhage following vaginal
      deliveries were twin deliveries (OR 6.8), retained placenta (OR 3.9) and
      inductions of labor (OR 2.2). For cesarean sections, twin deliveries had the
      strongest association with severe hemorrhage (OR 3.7) followed by general
      anesthesia (OR 3.0). Obstetric interventions became more frequent; elective
      cesarean sections increased from 2.4 to 4.9%, acute cesarean sections from 5.5 to
      8.9%, operative vaginal deliveries from 9.3 to 12.5%, inductions of labor from
      14.3 to 15.8% and augmentations of labor from 5.8 to 29.3%. CONCLUSIONS: The
      incidence of severe postpartum hemorrhage increased, and this may be related to
      more frequent use of obstetric interventions.

PMID- 20809868
TI  - Taking aim at Mer and Axl receptor tyrosine kinases as novel therapeutic targets
      in solid tumors.
AB  - IMPORTANCE OF THE FIELD: Axl and/or Mer expression correlates with poor prognosis
      in several cancers. Until recently, the role of these receptor tyrosine kinases
      (RTKs) in development and progression of cancer remained unexplained. Studies
      demonstrating that Axl and Mer contribute to cell survival, migration, invasion,
      metastasis and chemosensitivity justify further investigation of Axl and Mer as
      novel therapeutic targets in cancer. AREAS COVERED IN THIS REVIEW: Axl and Mer
      signaling pathways in cancer cells are summarized and evidence validating these
      RTKs as therapeutic targets in glioblastoma multiforme, NSCLC, and breast cancer
      is examined. A discussion of Axl and/or Mer inhibitors in development is
      provided. WHAT THE READER WILL GAIN: Potential toxicities associated with Axl or
      Mer inhibition are addressed. We propose that the probable action of Mer and Axl
      inhibitors on cells within the tumor microenvironment will provide a therapeutic
      opportunity to target both tumor cells and the stromal components that facilitate
      disease progression. TAKE HOME MESSAGE: Axl and Mer mediate multiple oncogenic
      phenotypes and activation of these RTKs constitutes a mechanism of
      chemoresistance in a variety of solid tumors. Targeted inhibition of these RTKs
      may be effective as anti-tumor and/or anti-metastatic therapy, particularly if
      combined with standard cytotoxic therapies.

PMID- 20809872
TI  - Successful treatment of auricular pseudocyst with clothing button bolsters alone.
AB  - Abstract Auricular pseudocyst is clinically characterized by asymptomatic, non
      inflammatory benign cystic swelling, usually located on the anterior or posterior
      helix. Recurrences have been observed frequently after simple drainage or
      aspiration of the lesions. Certain treatment modalities for the condition have
      been reported with variable success, complications and cosmetic results. These
      include intralesional steroid injection, sclerosing agent administration such as
      minocycline, fibrin glue, trichloracetic acid with or without compression,
      compressive treatment alone (e.g surgical bolsters, prosthesis) and surgical
      intervention. Here we report the successful treatment of an auricular pseudocyst
      using clothing button bolsters alone.

PMID- 20809873
TI  - Effects of progressive exercise during phase I cardiac rehabilitation on the
      heart rate variability of patients with acute myocardial infarction.
AB  - PURPOSE: Heart rate variability (HRV) decreases after an acute myocardial
      infarction (AMI) due to changes in cardiac autonomic balance. The purpose of the
      present study, therefore, was to evaluate the effects of a progressive exercise
      protocol used in phase I cardiac rehabilitation on the HRV of patients with post
      AMI. MATERIAL AND METHODS: Thirty-seven patients who had been admitted to
      hospital with their first non-complicated AMI were studied. The treated group
      (TG, n=21, age=52+/-12 years) performed a 5-day programme of progressive exercise
      during phase I cardiac rehabilitation, while the control group (CG, n=16,
      age=54+/-11 years) performed only respiratory exercises. Instantaneous heart rate
      (HR) and RR interval were acquired by a HR monitor (Polar(r)S810i). HRV was
      analysed by frequency domain methods. Power spectral density was expressed as
      normalised units (nu) at low (LF) and high (HF) frequencies, and as LF/HF.
      RESULTS: After 5 days of progressive exercise, the TG showed an increase in HFnu
      (35.9+/-19.5 to 65.19+/-25.4) and a decrease in LFnu and LF/HF (58.9+/-21.4 to
      32.5+/-24.1; 3.12+/-4.0 to 1.0+/-1.5, respectively) in the resting position
      (p<0.05). No changes were observed in the CG. CONCLUSIONS: A progressive
      physiotherapeutic exercise programme carried out during phase I cardiac
      rehabilitation, as supplement to clinical treatment increased vagal and decreased
      sympathetic cardiac modulation in patients with post-AMI.

PMID- 20809874
TI  - Development and content validation of the Wheelchair Use Confidence Scale: a
      mixed-methods study.
AB  - BACKGROUND: Confidence in one's ability to perform a given task can be a stronger
      predictor of performance than skill itself. There are currently no measures to
      assess confidence with manual wheelchair use. The objective of this study was to
      develop and assess the content validity of the Wheelchair Use Confidence Scale
      (WheelCon-M). METHOD: A two-phase mixed-methods design was used. Semi-structured
      interviews were conducted to generate items, followed by a Delphi survey for item
      selection. Persons who use a wheelchair, health care professionals, and
      researchers participated in both phases of the study. RESULTS: An 84-item
      WheelCon-M was developed based on the qualitative data. After the Delphi survey,
      a final 62-item WheelCon-M was composed of the following six areas (number of
      items per area): Negotiating the Physical Environment (33 items), Activities
      Performed using a Manual Wheelchair (11 items), Knowledge and Problem Solving (6
      items), Advocacy (4 items), Managing Social Situations (5 items) and Managing
      Emotions (3 items). CONCLUSION: This article reports the development and content
      validation of the WheelCon-M. As a scale to measure confidence with wheelchair
      use was not available prior to this work, clinicians now have a method of
      identifying individuals who have low confidence with wheelchair use.

PMID- 20809875
TI  - Predictors of unmet needs for communication and mobility assistive devices among
      youth with a disability: the role of socio-cultural factors.
AB  - PURPOSE: Despite the importance of ensuring access to assistive technology, high
      rates of underutilization remain. Relatively little is known about the
      characteristics of young people reporting unmet needs for assistive devices, so
      our study examined this further. METHOD: Data were analyzed using the 2006
      Participation and Activity Limitation Survey. Youth aged 15-24 were selected to
      explore the characteristics associated with those currently using or reporting
      unmet needs for communication or mobility devices (n = 15,817). RESULTS: Family
      structure and language spoken influenced the likelihood of using a communication
      device for two age subgroups. Meanwhile, language spoken influenced the
      likelihood of reporting unmet needs for communication assistive devices. The
      following factors influenced the likelihood of using a mobility device: age,
      gender, language spoken, income, family structure, and severity of impairment.
      Gender, geographic location, language spoken, family structure, duration and
      severity of impairment and presence of other impairments influenced the
      likelihood of reporting unmet needs for mobility devices. CONCLUSIONS: Clinicians
      need to pay particular attention to the socio-cultural factors of young clients
      transitioning to adult care.

PMID- 20809877
TI  - Self-concept of children with intellectual disability in mainstream settings.
AB  - BACKGROUND: Positive self-concept is an important educational outcome for
      individuals with disability. METHOD: Perceived competence and acceptance of 17
      children with intellectual disability, included in mainstream classes, were
      assessed using the Pictorial Scale of Perceived Competence and Social Acceptance
      for Young Children (PSPCSA) and compared with (a) independently rated academic
      work samples and measures of social status, and (b) measures of perceived
      competence and acceptance reported for other populations of individuals with and
      without disability. RESULTS: Perceived competence and acceptance were positive
      and comparable to previously reported results for individuals with disability and
      young children without disability. The children's perceived cognitive competence
      was not consistent with ratings of their work samples but their perceived peer
      acceptance was more consistent with peer ratings of social status. CONCLUSION:
      Children with intellectual disability remained positive at an age when self
      concept is likely to be negatively impacted by comparisons with higher performing
      peers.

PMID- 20809878
TI  - Maternal parenting stress in families with a child with Angelman syndrome or
      Prader-Willi syndrome.
AB  - BACKGROUND: Parenting stress was investigated in mothers with a child with
      Angelman syndrome (AS) or Prader-Willi syndrome (PWS), which are genetically
      related. METHOD: Mothers of 24 children with AS and 23 children with PWS (2-12
      years) completed the Nijmegen Parenting Stress Index-Short, Developmental
      Behaviour Checklist, and Vineland Screener 0-12. RESULTS: Parenting stress was
      high for 58% of AS and 26% of PWS cases. For both syndromes, no relationship
      existed with the child's gender, age, or behavioural problems. In PWS there was
      no effect on level of functioning. Overall, more mothers with a child with AS
      perceived high parenting stress. When children showed low levels of behavioural
      problems this difference was contained. However, when children exhibited severe
      behavioural problems, parenting stress was the same for both syndromes.
      CONCLUSION: In AS professional family support is essential, since parenting is
      stressful for many mothers. In PWS, this is especially the case when behavioural
      problems are present.

PMID- 20809879
TI  - The pearl in the middle: a case study of social interactions in an individual
      with a severe intellectual disability.
AB  - BACKGROUND: People with severe intellectual disability have limited communication
      skills, small social networks, and may experience isolation. Little is known
      about how interactions occur with social network members and the role of social
      support. METHOD: An adult with a severe intellectual disability was observed in
      her daily environments. Her social network members were identified and
      interviewed. Data were analysed using a grounded theory approach. RESULTS:
      Fourteen social network members were identified. People with severe intellectual
      disability interact in different ways, which may not be understood by network
      members or conform to normative expectations. Still, network members experienced
      enjoyment, personal satisfaction, and love in their interactions. CONCLUSIONS:
      Social interactions with people with severe intellectual disability are
      challenging. The results point to the benefits of a focus on learning that makes
      interactions meaningful for each individual, sharing that information with
      network members, and considering ways to increase interactions and extend the
      social network.

PMID- 20809880
TI  - The co-occurrence of nonaffective psychosis and the pervasive developmental
      disorders: a systematic review.
AB  - BACKGROUND: Pervasive developmental disorders (PDDs) were originally
      conceptualised as a form of ("infantile") psychosis. Recently, the disorders have
      been viewed as separate constructs. However, there is evidence of overlapping
      psychopathology, pathophysiology, and occurrence of the two syndromes. METHODS: A
      historical overview is provided. A systematic search strategy was then used to
      identify literature relating to the co-occurrence of PDD and nonaffective
      psychosis. RESULTS: The methodology and estimated rates of psychosis occurring in
      PDD varied dramatically, and few conclusions could be drawn due to the level of
      heterogeneity and selection bias in the populations studied. However, there were
      indications from the literature that rates of comorbid PDD were elevated in
      adolescents affected by juvenile-onset psychosis but the methodology was
      insufficiently robust to estimate a pooled prevalence. CONCLUSIONS: There is some
      evidence for elevated rates of comorbid PDD in individuals with childhood-onset
      psychosis. Further work is needed in order to understand the potential mechanisms
      underlying such co-occurrence and how such affected individuals can be best
      supported.

PMID- 20809882
TI  - Support staff working in intellectual disability services: the importance of
      relationships and positive experiences.

PMID- 20809881
TI  - The use of restrictive interventions in Victoria, Australia: population data for
      2007-2008.

PMID- 20809883
TI  - The potential for active mentoring to support the transition into retirement for
      older adults with a lifelong disability.

PMID- 20809886
TI  - Laryngotracheal stenosis in critically ill patients.
AB  - CONCLUSIONS: Prolonged artificial pulmonary ventilation by tracheostomy tube (>30
      days) doubled the risk of stenosis (relative risk, RR = 2.04, p = 0.002).
      Critically ill patients with repeated tracheotomies were more than six times
      likely to experience stenosis (RR = 6.44, p< 0.001) than other critically ill
      patients. OBJECTIVE: In this retrospective study, we describe the occurrence of
      laryngotracheal stenosis (LTS) in critically ill patients after elective
      tracheostomy who had undergone treatment for LTS at the Na Homolce Hospital in
      Prague, Czech Republic. METHODS: We studied 28 patients who were diagnosed with
      symptomatic LTS. Basic major demographic data, duration of mechanical
      ventilation, onset of tracheal stenosis after decannulation, and tracheostomy
      type (percutaneous dilatational or surgical tracheostomy) were recorded. The
      number of patients requiring repeated tracheostomies was also recorded. RESULTS:
      Neither the demographic data nor the type of tracheostomy represented
      statistically significant risk factors. The risk factors for LTS were prolonged
      artificial pulmonary ventilation using the tracheostomy tube (p = 0.005) and
      repeated tracheostomy (p< 0.001). The mean onset of stenosis symptoms was 53.7
      days (range 2-300 days), with a median of 58 days. Stenosis involved the trachea
      in 20 patients, subglottis in five cases, and glottis and subglottis in three
      cases. Seven patients (25%) underwent a tracheal resection and primary end-to-end
      reconstruction. One patient underwent laryngotracheoplasty with dilatation. The
      procedure was endoscopic in 18 patients (64.3%). Two patients (7.1%) received
      permanent tracheostomies.

PMID- 20809887
TI  - Analysis of acinic cell carcinoma of the parotid gland - 15 years experience.
AB  - CONCLUSION: In our experience, the prognosis for parotid gland acinic cell
      carcinoma (AciCC) is good. Surgery alone would be sufficient in early-stage
      tumor. Postoperative adjuvant treatment in advanced-stage patients or those with
      positive resection margins usually gives satisfactory control of the disease.
      OBJECTIVES: AciCC is a rare tumor in parotid gland malignancy. The aim of this
      study was to retrospectively analyze the experience in our hospital in treating
      this malignancy. METHODS: Twenty-five patients with AciCC diagnosed from 1983 to
      2007 at the Chang Gung Memorial Hospital were retrospectively reviewed. RESULTS:
      Thirteen male and 12 female patients ranged in age from 16 to 84 years (mean 37.5
      years) at the time of diagnosis. Most patients (92%) presented with symptoms of
      infra-auricular mass. The tumor stage distributions of the patients were 24%,
      44%, 28%, and 4% for stages I, II, III, and IV, respectively. Thirteen patients
      underwent superficial parotidectomy and 12 patients underwent total
      parotidectomy. Four patients had positive resection margins. Ten patients had
      surgery and postoperative radiotherapy; one received surgery and postoperative
      chemo/radiotherapy. The 10-year disease-free and overall actuarial survivals were
      both 84% in a mean follow-up of 75.8 months.

PMID- 20809888
TI  - HR MAS MR spectroscopy in metabolic characterization of cancer.
AB  - One of the central hallmarks of cancer is the rapid and infinite cellular
      proliferation. In order to cope with increased requirement for building blocks
      and energy, cancer cells develop abnormal metabolic properties. Detailed
      assessment of cancer cell metabolism can provide biological information for use
      in both drug discovery and development of personalized cancer therapy. Analysis
      of intact tissue using high resolution magic angle spinning (HR MAS) magnetic
      resonance spectroscopy (MRS) gives qualitative and quantitative metabolite
      measures with minimal sample preparation. Multivariate statistical methods are
      important tools for analysis of complex MR data and have in recent years been
      used for analysis of HR MAS data from intact tissue. HR MAS analysis of intact
      tissue allows combination of metabolomic data with genomic or proteomic data, and
      can therefore be used both for exploring the molecular biology of cancer and for
      clinical improvements in cancer diagnostics, prognostics and treatment planning.
      In this review, the basic concepts of HR MAS are presented, and its use in
      characterisation of cancer metabolism is discussed with specific focus on
      selected pathways such as choline metabolism and glycolysis. The use of HR MAS in
      analysis of amino acids and lipid metabolism in cancer is also reviewed. Finally,
      the expected role of HR-MAS in metabolic characterisation in the near future is
      discussed.

PMID- 20809889
TI  - NMR screening and hit validation in fragment based drug discovery.
AB  - Over the past three decades nuclear magnetic resonance spectroscopy has been
      developed into a mature technique for the characterization of interactions of
      small molecule ligands with their corresponding protein and nucleic acid
      receptors. In fact, a significant number of industrial and academic laboratories
      employ NMR for screening small molecule compound collections for binding to
      defined macromolecular targets, thus potentially providing initial, low affinity
      hits for a fragment-based approach in the drug discovery process. NMR is also
      applied to interrogate hits obtained by high throughput screening using
      biochemical assays and by virtual screening methods, for their ability to
      physically interact with the target receptor. In favorable cases a variety of NMR
      based methods can also provide essential information to validate the hit, rank
      the different hits according to affinity, and to structurally analyze the ligand
      target complex, thus providing essential information for structure-based
      optimization and medicinal chemistry. In this review a comprehensive overview of
      the large variety of NMR methods to study interactions between small molecule
      ligands and macromolecular receptors is provided, summarizing the physico
      chemical bases of the different receptor- and ligand-observed experiments. The
      application of these methods for compound library screening and hit validation,
      with special emphasis on their contribution to fragment-based drug discovery
      strategies, is illustrated by recent examples selected from the literature and
      work in my laboratory.

PMID- 20809890
TI  - High resolution magic angle spinning NMR applied to the analysis of organic
      compounds bound to solid supports.
AB  - In situ structural characterization of organic compounds attached to solid
      supports can be achieved by high-resolution magic angle spinning NMR (HRMAS NMR),
      a technique that provides solution-like spectra for resin-bound molecules. This
      review outlines the principles of the technique, the influence of the solid
      support on data quality, and NMR experiments that are useful for obtaining
      valuable information. The review describes, with multiple examples mainly from
      the last 7 years, how HRMAS NMR has been applied to monitor solid-phase
      reactions, elucidate reaction products and quantify compound loading on a solid
      support. Other applications, such as conformational analysis of immobilized
      compounds and investigation of molecular interactions with compounds in solution,
      are also discussed.

PMID- 20809891
TI  - Environmentally sensitive paramagnetic and diamagnetic contrast agents for
      nuclear magnetic resonance imaging and spectroscopy.
AB  - Even though alterations in the microenvironmental properties of tissues underlie
      the development of the most prevalent and morbid pathologies, they are not
      directly observable in vivo by Magnetic Resonance Imaging (MRI) or Spectroscopy
      (MRS) methods. This circumstance has lead to the development of a wide variety of
      exogenous paramagnetic and diamagnetic MRI and MRS probes able to inform non
      invasively on microenvironmental variables such as pH, pO(2), ion concentration o
      even temperature. This review covers the fundamentals of environmental contrast
      and the current arsenal of endogenous and exogenous MRI and MRS contrast
      enhancing agents available to visualize it. We begin describing the
      physicochemical background necessary to understand paramagnetic and diamagnetic
      contrast enhancement with a special reference to novel magnetization transfer and
      (13)C hyperpolarization strategies. We describe then the main macrocyclic
      structures used to support the environmentally sensitive paramagnetic sensors,
      including CEST and PARACEST pH sensitive probes, temperature probes and enzyme
      activity or gene expression activatable probes. Finally we address the most
      commonly used diamagnetic contrast agents including imidazolic derivatives to
      reveal extracellular pH and tissue pO(2) values by MRS. The potential
      applications of these agents in multimodal and molecular imaging approaches are
      discussed.

PMID- 20809892
TI  - Effect of drugs in cells and tissues by NMR spectroscopy.
AB  - In this article, the application of high resolution NMR spectroscopy to study the
      effect of therapeutic compounds on cells, tissues and organisms is reviewed. To
      illustrate how these NMR methods can provide useful information for a better
      understanding about the mechanism of action of drugs and their interactions with
      metabolic pathways, the emphasis is placed on most recent work about drug
      therapeutic intervention in biological models of diseases and in humans.
      Specifically, the application of NMR spectroscopy to investigate the effect of
      drugs on the treatment of neurological disorders, cancer, infectious diseases and
      diabetes is illustrated. In addition, NMR studies of drug-induced toxicity and
      multinuclear NMR for monitoring drug delivery and catabolism are described.
      Current progress in NMR instrumentation and methods will continue to improve the
      sensitivity and maintain this very versatile technique as powerful tool for
      research in the field of medicinal chemistry.

PMID- 20809893
TI  - Application of NMR spectroscopy in medicinal chemistry and drug discovery.
AB  - We describe the details of the magnetic resonance spectroscopy and chemical shift
      imaging techniques for the human brain which have been developed over the last
      two decades. With these non-invasive tools, it is now readily possible to
      repeatedly assay up to 20 common brain metabolites. From the perspective of drug
      discovery, each of these metabolites could fulfill a number of useful functions:
      disease biomarker, surrogate marker of drug delivery, surrogate marker of drug
      efficacy and so on. To facilitate the possible utility of clinical magnetic
      resonance spectroscopy in future drug discovery, the major portion of the review
      is devoted to a detailed description of the well-validated neurochemical profiles
      of many common human brain disorders, for which MRS data now exists. Beyond
      proton, MRS, the commonest tool provided by the manufacturers of clinical MRI
      equipment, lays the world of heteronuclear NMR more familiar to chemists. Here
      too, with relatively little effort it has been possible to define neurochemical
      profiles of human brain disorders using (13)C MRS in particular. The future for
      drug discovery scientists is discussed. Finally, recognizing that a known feature
      of MR is the lack of sensitivity, we describe new efforts to harness
      hyperpolarization, with its 50,000 signal amplification, to conventional MRS.

PMID- 20809894
TI  - Application of NMR spectroscopy in medicinal chemistry and drug discovery.
AB  - "In-cell nuclear magnetic resonance (NMR)" is a unique method for
      characterization of conformation, interaction and dynamics of proteins inside
      living cells at atomic level. Since the method was proposed by Dotch and co
      workers in 2001 [1], its application had been limited to bacterial cells and
      oocytes of Xenopus laevis [2]. Recently, we reported a method for efficient
      delivery of (15)N-labeled proteins into human HeLa cells using cell-penetrating
      peptides, and measured high-resolution two-dimensional (1)H-(15)N correlation
      spectra of proteins in the cells. The in-cell NMR spectroscopy in human cells is
      capable of analyzing structures, interactions, dynamics and stability of proteins
      inside cells. Of its possible applications, we propose that in-cell NMR
      spectroscopy can be utilized as an effective step in protein-targeted drug
      development process, by demonstrating that interaction of FKBP12 with
      immunosuppressants administered extracellularly was successfully observed in
      living cells. This observation suggests that drug delivery and capability of
      target proteins inside cells for interaction with drugs can be investigated by in
      cell NMR spectroscopy. More recently, an alternative way for intracellular
      delivery of labeled proteins for in-cell NMR was reported on 293F cells by
      Shimada and co-workers. Here, we review recent technical developments of in-cell
      NMR spectroscopy, and discuss potential usefulness for protein chemistry and drug
      screening process.

PMID- 20809895
TI  - Structure based design of 11beta-HSD1 inhibitors.
AB  - Controlling elevated tissue-specific levels of cortisol may provide a novel
      therapeutic approach for treating metabolic syndrome. This concept has spurred
      large scale medicinal chemistry efforts in the pharmaceutical industry for the
      design of 11beta-HSD1 inhibitors. High resolution X-ray crystal structures of
      inhibitors in complex with the enzyme have facilitated the structure-based design
      of diverse classes of molecules. A summary of binding modes, trends in structure
      activity relationships, and the pharmacodynamic data of inhibitors from each
      class is presented.

PMID- 20809896
TI  - Open access high throughput drug discovery in the public domain: a Mount Everest
      in the making.
AB  - High throughput screening (HTS) facilitates screening large numbers of compounds
      against a biochemical target of interest using validated biological or
      biophysical assays. In recent years, a significant number of drugs in clinical
      trails originated from HTS campaigns, validating HTS as a bona fide mechanism for
      hit finding. In the current drug discovery landscape, the pharmaceutical industry
      is embracing open innovation strategies with academia to maximize their research
      capabilities and to feed their drug discovery pipeline. The goals of academic
      research have therefore expanded from target identification and validation to
      probe discovery, chemical genomics, and compound library screening. This trend is
      reflected in the emergence of HTS centers in the public domain over the past
      decade, ranging in size from modestly equipped academic screening centers to well
      endowed Molecular Libraries Probe Centers Network (MLPCN) centers funded by the
      NIH Roadmap initiative. These centers facilitate a comprehensive approach to
      probe discovery in academia and utilize both classical and cutting-edge assay
      technologies for executing primary and secondary screening campaigns. The various
      facets of academic HTS centers as well as their implications on technology
      transfer and drug discovery are discussed, and a roadmap for successful drug
      discovery in the public domain is presented. New lead discovery against
      therapeutic targets, especially those involving the rare and neglected diseases,
      is indeed a Mount Everestonian size task, and requires diligent implementation of
      pharmaceutical industry's best practices for a successful outcome.

PMID- 20809897
TI  - Pathway-specific, species, and sub-type counterscreening for better GPCR hits in
      high throughput screening.
AB  - G protein-coupled receptors represent one of the largest families of drug
      targets. Time and cost may be saved if GPCR modulators are assessed in terms of
      signaling pathway selectivity, species selectivity, and selectivity against
      closely-related family members early in the drug discovery process, perhaps even
      at the stage of high-throughput screening. Examples are given of how these kinds
      of selectivity have been addressed during screening.

PMID- 20809898
TI  - Taking a systems approach to the identification of novel therapeutic targets and
      biomarkers.
AB  - Systems biology focuses on the roles of cellular pathways and networks rather
      than single biomolecules to describe biological function. A systems view of
      biology requires technology that can generate and quantitatively analyze, large
      multi-dimensional data sets from many different sources. New technology has made
      this approach to drug discovery increasingly feasible. Detailed changes in
      cellular phenotype can be quantitatively measured using high content phenotypic
      screens. Changes in a cells entire transcriptome or proteome can be profiled in
      detail. Libraries of small molecules, peptides or poly-nucleotides such as siRNA
      can be screened to identify perturbagens that modulate transcriptomic, proteomic
      and cellular phenotypic signatures. These molecular agents can be used to
      deconvolute pathways and networks. The power of these technologies lies in their
      ability to generate complex biological data at massive scales. Integration and
      analysis of this multi-parametric data is vital to systems biology research.
      Patterns and relationships within these data sets can be revealed using factor
      and principal component analysis. These patterns can point to pathways that are
      relevant to specific biological processes making the ultimate goal of
      understanding the biology of a cell at the systems level possible.

PMID- 20809899
TI  - Structural investigation of myo-inositol dehydrogenase from Bacillus subtilis:
      implications for catalytic mechanism and inositol dehydrogenase subfamily
      classification.
AB  - Inositol dehydrogenase from Bacillus subtilis (BsIDH) is a NAD+-dependent enzyme
      that catalyses the oxidation of the axial hydroxy group of myo-inositol to form
      scyllo-inosose. We have determined the crystal structures of wild-type BsIDH and
      of the inactive K97V mutant in apo-, holo- and ternary complexes with inositol
      and inosose. BsIDH is a tetramer, with a novel arrangement consisting of two long
      continuous beta-sheets, formed from all four monomers, in which the two central
      strands are crossed over to form the core of the tetramer. Each subunit in the
      tetramer consists of two domains: an N-terminal Rossmann fold domain containing
      the cofactor-binding site, and a C-terminal domain containing the inositol
      binding site. Structural analysis allowed us to determine residues important in
      cofactor and substrate binding. Lys97, Asp172 and His176 are the catalytic triad
      involved in the catalytic mechanism of BsIDH, similar to what has been proposed
      for related enzymes and short-chain dehydrogenases. Furthermore, a conformational
      change in the nicotinamide ring was observed in some ternary complexes,
      suggesting hydride transfer to the si-face of NAD+. Finally, comparison of the
      structure and sequence of BsIDH with other putative inositol dehydrogenases
      allowed us to differentiate these enzymes into four subfamilies based on six
      consensus sequence motifs defining the cofactor- and substrate-binding sites.

PMID- 20809900
TI  - Shiga toxin 1 and ricin A chain bind to human polymorphonuclear leucocytes
      through a common receptor.
AB  - The main cause of acute renal failure in children is HUS (haemolytic uraemic
      syndrome), a consequence of intestinal infections with Escherichia coli strains
      producing Stx (Shiga toxins). Stx released in the gut by the non-invasive
      bacteria reach the bloodstream and are targeted to cerebral and renal endothelium
      triggering HUS. PMN (polymorphonuclear leucocytes) seem to be involved in Stx
      delivery through an unidentified membrane receptor (Kd=10-8 M; 2*105 binding
      sites) which does not allow internalization. Some experts in the field have
      defined the Stx-PMN interaction as non-specific and of little biological
      significance. In the present study, we show that the A chain of ricin, the well
      known plant RIP (ribosome-inactivating protein), interacts with PMN (Kd=10-9 M;
      2*105 binding sites) competing for the same receptor that recognizes Stx, whereas
      diphtheria toxin and several agonists of TLRs (Toll-like receptors) or the
      mannose receptor were ineffective. No toxic effects of ricin A chain on PMN were
      observed, as assessed by measuring protein synthesis and the rate of spontaneous
      apoptosis of leucocytes. Moreover, two single-chain RIPs (gelonin and saporin S6)
      had the same competing effect. Thus RIPs and Stx1 share structural similarities,
      the same enzymatic activity and a common receptor on PMN. These observations
      reveal that the Stx-PMN interaction is specific, confirming that PMN recognize
      molecular patterns common to different foreign molecules.

PMID- 20809901
TI  - Biochemical and thermodynamic characterization of mutated beta1,4
      galactosyltransferase 7 involved in the progeroid form of the Ehlers-Danlos
      syndrome.
AB  - Three mutations of the B4GALT7 gene [encoding beta1,4-GalT7 (beta1,4
      galactosyltransferase 7)], corresponding to A186D, L206P and R270C, have been
      identified in patients with the progeroid form of the Ehlers-Danlos syndrome and
      are described as being associated with the reduction or loss of beta1,4-GalT7
      activity. However, the molecular basis of the reduction or loss of activity
      remained to be determined. In the present study, wild-type, A186D, L206P and
      R270C beta1,4-GalT7 were expressed in CHO618 cells as membrane proteins and in
      Escherichia coli as soluble proteins fused to MBP (maltose-binding protein). The
      ability of the expressed proteins to transfer galactose from donor to acceptor
      substrates was systematically characterized by kinetic analysis. The
      physicochemical properties of soluble proteins were explored by isothermal
      titration calorimetry, which is a method of choice when determining the
      thermodynamic parameters of the binding of substrates. Together, the results
      showed that: (i) the L206P mutation abolished the activity when L206P
      beta1,4GalT7 was either inserted in the membrane or expressed as a soluble MBP
      full-length fusion protein; (ii) the A186D mutation weakly impaired the binding
      of the donor substrate; and (iii) the R270C mutation strongly impaired the
      binding of the acceptor substrate. Moreover, the ex vivo consequences of the
      mutations were investigated by evaluating the priming efficiency of xylosides on
      GAG (glycosaminoglycan) chain initiation. The results demonstrate a quantitative
      effect on GAG biosynthesis, depending on the mutation; GAG biosynthesis was fully
      inhibited by the L206P mutation and decreased by the R270C mutation, whereas the
      A186D mutation did not affect GAG biosynthesis severely.

PMID- 20809902
TI  - Clinical features of Sjogren's syndrome in patients with multiple sclerosis.
AB  - OBJECTIVES:   To assess the frequency of clinical features of Sjogren's syndrome
      (SS) in patients with multiple sclerosis (MS) receiving treatment with disease
      modifying drugs (DMDs) or naive to treatment and the possible association with
      clinical, cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI)
      parameters. METHODS:   A multicentre cross-sectional observational study was
      designed, based on a structured neurologist-administered questionnaire to 440
      patients. RESULTS:   Twenty-eight of 230 (12%) patients receiving treatment with
      DMDs (DMDs(+)) and 14 of 210 (6.6%) treatment-naive patients (DMDs(-) ) showed
      clinical features of SS. Four primary SS were diagnosed, two of which were
      DMDs(+) and two were DMDs(-) . Sicca symptoms were significantly associated with
      higher EDSS scores (P = 0.018), a low frequency of gadolinium-enhanced MRI
      positive lesions (P = 0.018) and cerebral disturbances (P = 0.001). CONCLUSIONS:
      Screening for the clinical features of SS should be performed in patients with MS
      both receiving treatment with immunomodulatory drugs and without therapy.

PMID- 20809903
TI  - Dynamic cerebral autoregulation in stroke patients with a central sympathetic
      deficit.
AB  - OBJECTIVE: To investigate the functional role of the sympathetic innervation on
      cerebral autoregulation. MATERIALS AND METHODS: Seventeen patients with
      infarction of the dorsolateral medulla oblongata affecting central sympathetic
      pathways (Wallenberg's syndrome) and 21 healthy controls were included in the
      study. Cerebral blood flow velocity (CBFV) in the medial cerebral artery was
      investigated using transcranial Doppler ultrasound during decrease in cerebral
      perfusion pressure induced by leg-cuff test and tilt table. RESULTS: Upon leg
      cuff test, changes of cerebral blood flow and mean arterial blood pressure as
      well as autoregulatory index did not differ between patients or controls. No
      differences were found in changes of CBFV, mean arterial blood pressure and heart
      rate between patients or controls during the tilt table test. CONCLUSIONS: We
      suggest that the sympathetic nervous system does not have an influence on
      cerebral autoregulation after decrease in perfusion pressure under normotonous
      conditions.

PMID- 20809904
TI  - Infiltrating macrophages in extratumoural tissues after brachytherapy of uveal
      melanoma.
AB  - PURPOSE: To compare distribution of macrophages in extratumoural ocular tissues
      in enucleated eyes with irradiated and nonirradiated uveal melanomas to find out
      how irradiation affects distribution of macrophages so as to gain insight into
      their potential routes of migration and changes in local inflammatory responses.
      METHODS: Thirty-four matched pairs of primarily enucleated nonirradiated and
      secondarily enucleated irradiated eyes with choroidal and ciliary body melanoma
      were stained with mAb PG-M1, and the extratumoural immunopositive elements were
      counted under the microscope. Main outcome variables were the number of
      macrophages in the sclera underlying the tumour, in the choroid adjacent to the
      tumour, and in the ciliary body. The number of macrophage aggregates in the
      anterior ipsi- and contralateral episclera adjacent to the limbus was also
      counted. RESULTS: Macrophages were more numerous within the sclera under the
      tumour in irradiated eyes when compared to primarily enucleated eyes (median 1514
      versus 619/mm2, p = 0.0001), and more aggregates of episcleral macrophages
      adjacent to the limbus were found after irradiation (ipsilateral side, median 132
      versus 0, p = 0.0034; contralateral side, median 79 versus 0, p = 0.014). In
      primarily enucleated eyes, increasing numbers of tumour-infiltrating macrophages
      were associated with presence of higher numbers of macrophages in the ciliary
      body (p = 0.003) and the adjacent choroid (p = 0.044), whereas in the irradiated
      eyes, increasing numbers of tumour-infiltrating macrophages (p = 0.010) and
      increasing extent of necrosis (p < 0.001) were associated with higher numbers of
      intrascleral macrophages underlying the tumour. CONCLUSIONS: Resident macrophages
      are present in extratumoural tissues in eyes with uveal melanoma. Brachytherapy
      may alter their route of migration and increase the number of macrophages in the
      sclera and episclera. Histopathologically detectable episcleral aggregates of
      macrophages adjacent to the limbus are detected predominantly after irradiation,
      a population of which is clinically visible as episcleral deposits after
      irradiation.

PMID- 20809905
TI  - Symptoms related to glaucomatous visual field abnormalities among male Japanese
      workers in a population-based setting.
AB  - PURPOSE: To identify symptoms potentially related to glaucomatous visual field
      abnormalities (VFAs) in a population-based setting, and to assess the
      applicability of using these symptoms to identify persons at risk of developing
      glaucoma. METHODS: In this study, 10,214 Japanese male general workers (mean age,
      45.3+/-8.8 years) filled out a self-administered questionnaire and underwent
      frequency doubling technology (FDT) perimetry testing. The questionnaire inquired
      about whether the participant was suffering from any of nine symptoms, with
      scores for each response graded on a four-item Likert scale: 0 (none), 1
      (rarely), 2 (sometimes), and 3 (always). Results from the questionnaire were
      compared among three groups: participants without any VFAs (9767), participants
      with VFAs as determined by the FDT test (FDT-VFA; 447), and 227 participants (of
      the 447 FDT-VFA participants) with glaucomatous VFAs who were newly diagnosed by
      ophthalmologic examinations. RESULTS: The mean summed scores for the total items
      were significantly (p<0.01) higher in FDT- and glaucomatous VFA groups than in
      normal subjects. In particular, responses citing the symptoms 'feeling of
      something in the front of the eye' and 'feeling of hardness to see in dark
      places' were significantly (p<0.05) more frequent in subjects with FDT- and
      glaucomatous VFAs than among normal participants. However, the respective areas
      under the receiver operating characteristic curve of summed scores for the nine
      total items and for the two items which showed significant differences for the
      glaucoma groups were 0.57 (95% confidence interval=0.53-0.60) and 0.58 (95%
      confidence interval=0.54-0.61). CONCLUSION: Although the symptoms 'feeling of
      hardness to see in dark places' and 'feeling of something in the front of the
      eye' could be associated with glaucomatous VFA in a population-based setting,
      inquiring about symptoms is of little aid in identifying subjects with
      glaucomatous VFA as a strategy for public health.

PMID- 20809906
TI  - Local retinal sensitivity in relation to specific retinopathy lesions in diabetic
      macular oedema.
AB  - PURPOSE: To study microperimetric macular sensitivity in diabetic macular oedema
      (DMO) in relation to lesion characteristics obtained by optical coherence
      tomography (OCT), colour fundus photography, and fluorescein angiography (FA).
      METHODS: The study comprised 20 eyes in 15 patients with nonproliferative
      diabetic retinopathy and recently diagnosed untreated DMO. Investigations
      included microperimetry, fluorescein angiography, colour fundus photography, and
      OCT. All measures and gradings were made for each of the nine fields of an early
      treatment diabetic retinopathy study macula template. Statistical analysis was
      made using Spearman's nonparametric test including field and mean values within
      fields. Comparisons were made within the study population and with a normative
      microperimetry database. RESULTS: Subnormal microperimetric sensitivity was
      associated with cystoid macular oedema, both in foveal petaloid (r = -0.50, p =
      0.02) and extrafoveal honeycomb patterns (r = -0.8, p < 0.0001) and with outer
      nuclear layer cysts (r = -0. 5, p = 0.024), inner nuclear layer cysts (r = -0.31,
      p = 0.03), and hard exudate (r = -0.38, p = 0.0026). There was no detectable
      effect of focal noncystoid oedema (r = -0.16, p = 0. 48), diffuse noncystoid
      oedema (r = -0.14, p = 0.55), capillary nonperfusion (r = -0.33, p = 0.15),
      intraretinal haemorrhage (r = -0.15, p = 0.53), or serous retinal detachment (r =
      -0.11, p = 0.63). Foveal thickening was associated with locally reduced
      sensitivity (r = -0.54, p = 0.01). Foveal sensitivity was positively correlated
      to the visual acuity, with a correlation of 0.44 and a borderline significance (p
      = 0.0509). CONCLUSIONS: Macular hard exudates and cystoid oedema were associated
      with locally reduced sensitivity. Thus, the lesions associated with reduced
      sensitivity for a white-on-white stimulus were such lesions that cause light to
      be blocked or scattered before it reaches the photoreceptors, suggesting that
      optical effects are a major cause of sensitivity loss.

PMID- 20809907
TI  - Cerebral migration of intraocular silicone oil: an MRI study.
AB  - BACKGROUND: Intraocular silicone oil may migrate into the optic nerve or the
      cerebral ventricles, but little is known about the frequency of these events. The
      aim of this prospective neuroimaging study was to determine the frequency of
      extraocular silicone oil migration in humans operated for retinal detachment.
      METHODS: Nineteen patients included in this study were referred for silicone oil
      removal after uncomplicated retinal detachment surgery using internal silicone
      oil tamponade. Patients with a previous history of intraocular silicone oil,
      glaucoma or optic pit were excluded. After informed consent, the patients
      underwent magnetic resonance imaging (MRI). Fat saturation as well as short T1
      inversion recovery (STIR) sequences combined with water saturation allowed
      silicone oil to be easily detectable. RESULTS: The mean delay between the
      silicone oil injection and the MRI procedure was 115 days. No extraocular
      silicone oil in the orbit, in the optic nerve or in the cerebral ventricles was
      found on MRI. CONCLUSIONS: This is the first published in vivo study on the
      frequency of extraocular silicone oil migration after retinal detachment surgery.
      Special dedicated MRI sequences are able to accurately visualize intraocular
      silicone oil. None of the included 19 patients were detected with silicone oil
      migration into the visual pathways or intracranially, suggesting that its
      occurrence may be very rare, maybe only in patients with optic nerve head
      anatomical predispositions.

PMID- 20809908
TI  - In vivo evaluation of photoreceptor mosaic in type 2 idiopathic macular
      telangiectasia using adaptive optics.

PMID- 20809909
TI  - Juvenile glaucoma in a child with caudal regression syndrome.

PMID- 20809910
TI  - Retinopathy and visual impairment in diabetes, impaired glucose tolerance and
      normal glucose tolerance: the Nord-Trondelag Health Study (the HUNT study).
AB  - PURPOSE: The aim of the study was to describe the prevalence of visual impairment
      and retinopathy and to investigate risk factors for retinopathy in persons with
      diabetes, screen-detected diabetes, impaired glucose tolerance and normal glucose
      tolerance in a subpopulation of the HUNT study. METHODS: We used a sample (n =
      163) from a population-based screening survey of hyperglycaemia, undertaken in
      2004-2005 in Verdal, Norway. Baseline information was accessible through the
      second Nord-Trondelag Health Study (HUNT2), 1995-97. Data collection was made in
      2005 and included patient history, refraction, visual acuity, cataract assessment
      and single-field, nonmydriatic retinal photography. Retinal photographs were
      graded independently by two graders blinded to patient information. Data were
      analysed with standard statistical methods, and p < 0.05 was considered
      significant. RESULTS: In all, 126 (77%) persons participated, 55% were women. The
      mean (SD) age was 59 (+/- 14) years. Four (3%) had correctable visual impairment,
      and none were visually impaired. Retinal photographs were gradable for both eyes
      in 109 (87%) participants. The prevalence of retinopathy was 11% in persons with
      known diabetes, 4% in persons with screen-detected diabetes, 3% in persons with
      impaired glucose tolerance and 10% in persons with normal glucose tolerance.
      Retinopathy was not associated with known history of diabetes or current
      glycaemic status. Nonfasting plasma glucose (in 1995-97) was an independent risk
      factor for retinopathy (in 2005), OR (95% CI) 1.5 (1.01, 2.13), p = 0.046.
      CONCLUSION: The prevalence of diabetic retinopathy in persons with diabetes in
      this study was low. Appropriate optical correction and regular eye examination
      can prevent unnecessary visual impairment in both persons with and without
      diabetes.

PMID- 20809911
TI  - Comorbidities of dry eye disease: a nationwide population-based study.
AB  - PURPOSE: To investigate the comorbidities of dry eye disease in a nationwide
      population-based data in Taiwan. METHODS: This study features a study group and a
      comparison group. The study group comprised 12 007 patients who sought ambulatory
      care for treatment of dry eye in 2005 and 2006. In total, 36 021 randomly
      selected patients were in the comparison group. Conditional logistic regression
      analyses conditioned on gender, age, monthly income and level of urbanization of
      the community in which the patient resided were conducted to calculate the odds
      ratio (OR) for each of 33 comorbidities among patients with and without dry eye
      disease. RESULTS: The regression analyses revealed that compared to patients
      without dry eye disease, patients with dry eye disease were more likely to have
      comorbidities of ischaemic heart disease (OR = 1.36), hyperlipidaemia (OR =
      1.68), cardiac arrhythmias (OR = 1.55), peripheral vascular disorders (OR =
      1.57), stroke (OR = 1.31), migraines (OR = 1.76), myasthenia gravis (OR = 2.85),
      RA (OR = 2.86), systemic lupus erythematosus (OR = 3.98), asthma (OR = 1.25),
      pulmonary circulation disorders (OR = 1.37), diabetes with complications (OR =
      1.31), hypothyroidism (OR = 1.94), liver diseases (OR = 1.71), peptic ulcers (OR
      = 1.76), hepatitis B (OR = 1.64), deficiency anaemias (OR = 1.31), depression (OR
      = 2.11), psychoses (OR = 1.87) and solid tumours without metastasis (OR = 1.41).
      CONCLUSIONS: This study demonstrates significantly higher prevalence of medical
      comorbidities in patients with dry eye disease in Taiwan.

PMID- 20809912
TI  - Angiotensin receptor blockade not related to history of dry eye symptoms and
      treatment in The Diabetic Retinopathy Candesartan Trials (DIRECT).

PMID- 20809913
TI  - Seasonal influence in wet age-related macular degeneration.

PMID- 20809914
TI  - Potential consequences of replacing a retail alcohol monopoly with a private
      licence system: results from Sweden.
AB  - AIM: To examine the potential effects of replacing the Swedish alcohol retail
      system with a private licensing system on alcohol consumption and alcohol-related
      harm. DESIGN: Two possible scenarios were analysed: (1) replacing the current
      alcohol retail monopoly with private licensed stores that specialize in alcohol
      sales or (2) making all alcohol available in grocery stores. We utilized a
      multiplicative model that projected effects of changes in a set of key factors
      including hours of sale, retail prices, promotion and advertising and outlet
      density. Next, we estimated the effect of the projected consumption increase on a
      set of harm indicators. Values for the model parameters were obtained from the
      research literature. MEASUREMENTS: Measures of alcohol-related harm included
      explicitly alcohol-related mortality, accident mortality, suicide, homicide,
      assaults, drinking driving and sickness absence. FINDINGS: According to the
      projections, scenario 1 yields a consumption increase of 17% (1.4 litres/capita),
      which in turn would cause an additional 770 deaths, 8500 assaults, 2700 drinking
      driving offences and 4.5 million sick days per year. The corresponding figures
      for scenario 2 are a consumption increase of 37.4% (3.1 litres/capita) leading to
      an additional annual toll of 2000 deaths, 20 000 assaults, 6600 drinking driving
      offences and 11.1 million days of sick leave. CONCLUSIONS: Projections based on
      the research literature suggest that privatization of the Swedish alcohol retail
      market would significantly increase alcohol consumption and alcohol-related harm.

PMID- 20809915
TI  - Gross anatomy and ultrasonographic images of the reproductive system of the
      Malayan tapir (Tapirus indicus).
AB  - The Malayan tapir (Tapirus indicus) is the largest among the four tapir species
      and is listed as an endangered species. Ultrasound examination and description of
      the external anatomy of the female reproductive system of three adult females
      were performed, whereas the internal anatomy was investigated in necropsied
      samples of four adult females and one subadult female. Descriptions of the male
      external genitalia were conducted on one adult male. Gross examination revealed
      the presence of a bicornuate uterus. The uterine cervix is firm and muscular with
      projections towards its lumen, which is also evident on ultrasonography. The
      elongated and relatively small ovaries, which have a smooth surface, could not be
      imaged on ultrasonography, due to their anatomical position. The testes are
      located inside a slightly pendulous scrotum that is sparsely covered with soft,
      short hairs. The penis has one dorsal and two lateral penile projections just
      proximal to the glans penis.

PMID- 20809916
TI  - Anatomical, histological and immunohistochemical study of the reproductive system
      accessory glands in male viscacha (Lagostomus maximus maximus).
AB  - The anatomy, histology and androgen receptor immunohistochemistry of the prostate
      (P), seminal vesicles (SV), bulbourethral and coagulant gland (CG) were studied
      in male viscacha, a seasonally reproductive wild rodent. Two histologically well
      defined zones, peripheral and central, were identified in the prostate, according
      to their relationship with the urethra. The epithelial cells were periodic acid
      Schiff (PAS)-positive in the central zone and alcian blue negative in the two
      zones. The SV are a paired gland, tubular, of tortuous aspect and formed by
      radial layers. The bulbourethral glands were paired, formed by tubuloalveolar
      acini and surrounded by a thick layer of skeletal muscle. The CG was
      multilobulated. The large adenomers showed PAS-positive epithelium and were
      negative to alcian blue. Androgen receptors in the P, SV and coagulating gland
      showed variations in their distribution with immunohistochemistry heterogeneous
      pattern. Finally, the reproductive system accessory glands of male viscacha may
      be considered as a novel and interesting model for the study of seasonal
      reproduction in photoperiod-dependent animals.

PMID- 20809917
TI  - Expression of putative stem cell markers related to developmental stage of sheep
      mammary glands.
AB  - It is thought that the regenerative capacity of the mammary gland following post
      lactation involution resides in multipotent stem cells within the luminal tissue.
      Adult stem cells make up a small percentage of the cells found in mature organ
      systems, however to define useful markers has long been a challenge. c-Kit (KIT)
      and its ligand stem cell factor (KITLG), ATP-binding cassette sub-family G member
      2 (ABCG2) and Musashi 1 (MSI1) are good candidate to identify progenitor cells in
      their niche. Using real-time PCR we showed that KIT, KITLG and MSI1 expressions
      were up regulated before lambing and at involution relatively to prepubertal
      stage. The in situ hybridization analysis for KIT gene confirmed and localized
      the expression in luminal epithelial cells. The changes in the expression profile
      of putative stem cell markers in mammary glands of sheep suggest that they modify
      with the progression of lactation cycle, being up regulated during
      differentiation and down regulated during lactation.

PMID- 20809918
TI  - Analysis of immune cells within the healthy oral mucosa of specific pathogen-free
      cats.
AB  - The oral mucosa is an important interface for host-environment interactions.
      Based on previous studies, it is generally accepted that the cellular
      compartments of the oral immune system comprise organized mucosal-associated
      lymphoid tissues as well as diffusely and focally distributed T- and to lesser
      extent B-lymphocytes, oral mucosal Langerhans cells (OMLC), macrophages and mast
      cells. However, a comprehensive quantification of the cellular elements in the
      oral mucous membranes of the cat has not been reported. The aim of this study was
      to provide a comprehensive analysis of the immune cell compartments in the oral
      mucous membranes and anatomically related tissues of healthy cats. Multiple
      biopsies of the oral mucous membranes and related tissues were obtained from four
      specific pathogen-free cats for histological and immunohistochemical assessment
      of lymphocyte subsets, OMLC, macrophages and mast cells. T-lymphocyte subsets,
      OMLC, mast cells and macrophages were present in varying frequencies among the
      tissue compartments of the feline oral cavity. B-lymphocytes were not identified
      in any of the examined tissues except the tonsils and mandibular lymph nodes.
      Lymphocytic aggregates (follicles) were found in the palatoglossal folds and the
      gingiva. We describe the topographical distribution of various leucocyte subsets
      in the normal healthy feline oral mucosa, and demonstrate regional differences in
      the distribution of these cells.

PMID- 20809919
TI  - The sheep genome reference sequence: a work in progress.
AB  - Until recently, the construction of a reference genome was performed using Sanger
      sequencing alone. The emergence of next-generation sequencing platforms now means
      reference genomes may incorporate sequence data generated from a range of
      sequencing platforms, each of which have different read length, systematic biases
      and mate-pair characteristics. The objective of this review is to inform the
      mammalian genomics community about the experimental strategy being pursued by the
      International Sheep Genomics Consortium (ISGC) to construct the draft reference
      genome of sheep (Ovis aries). Component activities such as data generation,
      sequence assembly and annotation are described, along with information concerning
      the key researchers performing the work. This aims to foster future participation
      from across the research community through the coordinated activities of the
      consortium. The review also serves as a 'marker paper' by providing information
      concerning the pre-publication release of the reference genome. This ensures the
      ISGC adheres to the framework for data sharing established at the recent Toronto
      International Data Release Workshop and provides guidelines for data users.

PMID- 20809921
TI  - A multispecies perspective on ecological impacts of climatic forcing.
AB  - 1. In the prevailing context of concerns over climate change and its potential
      impacts on ecosystems, evaluating ecological consequences of climatic forcing has
      become a critical issue. 2. Historical data on the abundance of organisms have
      been extensively used to characterize the ecological effects of climatic forcing
      through specific weather and/or climatic variables, with most of the studies
      confined to single population models. 3. However, population responses to
      environmental fluctuations typically depend upon positive and negative feedbacks
      induced by interactions with other species. It is therefore important to
      integrate the insights gained from single population approaches into a
      multispecies perspective. 4. Here we combine the hierarchical Bayesian modelling
      approach with the state-space formulation to extend the scope of previously
      proposed models of population dynamics under climatic forcing to multi-species
      systems. 5. We use our model to analyse long-term macro-moth (Lepidoptera)
      community data from the Rothamsted Insect Survey network in the UK, using winter
      rainfall and winter temperature as environmental covariates. 6. The effects of
      the two weather variables were consistent across species, being negative for
      winter rainfall and positive for winter temperature. The two weather variables
      jointly explained 15-40% of the total environmental variation affecting the
      dynamics of individual species, and could explain up to 90% of covariances in
      species dynamics. 7. The contribution of interspecific interactions to community
      level variation was found to be weak compared to the contributions of
      environmental forcing and intraspecific interactions.

PMID- 20809922
TI  - Chronic kidney disease: a public health priority and harbinger of premature
      cardiovascular disease.
AB  - The epidemics of cardiovascular disease, obesity, diabetes, HIV and cancer have
      all received much attention from the public, media and policymakers. By contrast,
      chronic kidney disease (CKD) has remained largely a 'silent' epidemic. This is
      unfortunate because early diagnosis of renal disease based on proteinuria and/or
      reduced estimated glomerular filtration rate could enable early intervention to
      reduce the high risks of cardiovascular events, end-stage renal disease (ESRD)
      and death that are associated with CKD. Given the global increase in the
      incidence of the leading causes of CKD--hypertension, obesity and diabetes
      mellitus--better disease management and prevention planning are needed, as
      effective strategies are available to slow the progression of CKD and reduce
      cardiovascular risk. CKD may be regarded as a clinical model of accelerated
      vascular disease and premature ageing, and the risk-factor profile changes during
      the progression from mild/moderate CKD to ESRD. Although many randomized
      controlled trials in patients with mild to moderate CKD have shown beneficial
      effects of interventions aimed at preventing the progression of CKD, most trials
      have been unable to demonstrate a beneficial effect of interventions aimed at
      improving outcome in ESRD. Thus, novel treatment strategies are needed in this
      high-risk patient group.

PMID- 20809923
TI  - Multi-locus sequence typing of Salmonella enterica serovar Typhimurium isolates
      from wild birds in northern England suggests host-adapted strain.
AB  - AIMS: Recent studies have suggested that Salmonella Typhimurium strains
      associated with mortality in UK garden birds are significantly different from
      strains that cause disease in humans and livestock and that wild bird strains may
      be host adapted. However, without further genomic characterization of these
      strains, it is not possible to determine whether they are host adapted. The aim
      of this study was to characterize a representative sample of Salm. Typhimurium
      strains detected in wild garden birds using multi-locus sequence typing (MLST)to
      investigate evolutionary relationships between them. METHODS AND RESULTS: Multi
      locus sequence typing was performed on nine Salm. Typhimurium strains isolated
      from wild garden birds. Two sequence types were identified, the most common of
      which was ST568. Examination of the public Salmonella enterica MLST database
      revealed that only three other ST568 isolates had been cultured from a human in
      Scotland. Two further isolates of Salm. Typhimurium were determined to be ST19.
      CONCLUSIONS: Results of MLST analysis suggest that there is a predominant strain
      of Salm. Typhimurium circulating among garden bird populations in the United
      Kingdom, which is rarely detected in other species, supporting the hypothesis
      that this strain is host adapted. SIGNIFICANCE AND IMPACT OF THE STUDY: Host
      pathogen evolution is often assumed to lead to pathogens becoming less virulent
      to avoid the death of their host; however, infection with ST568 led to high
      mortality rates among the wild birds examined, which were all found dead at wild
      bird-feeding stations. We hypothesize that by attracting unnaturally high
      densities of birds, wild bird-feeding stations may facilitate the transmission of
      ST568 between wild birds, therefore reducing the evolutionary cost of this
      pathogen killing its host, resulting in a host-adapted strain with increased
      virulence.

PMID- 20809924
TI  - Impacts of single-walled carbon nanotubes on microbial community structure in
      activated sludge.
AB  - AIMS: Single-walled carbon nanotubes (SWNTs) are likely to become increasingly
      widespread and yet their environmental impact is not well understood. The purpose
      of the current study was to evaluate the impact of SWNTs on microbial communities
      in a 'sentinel' environmental system, activated sludge batch-scale reactors.
      METHODS AND RESULTS: Triplicate batch reactors were exposed to SWNTs and compared
      to control reactors exposed to impurities associated with SWNTs. Automated
      ribosomal intergenic spacer analysis (ARISA) was used to assess bacterial
      community structure in each reactor. SWNT exposure was found to impact microbial
      community structure, while SWNT-associated impurities had no effect, compared to
      controls. 16S rRNA gene sequence analysis indicated that dominant phylotypes
      detected by ARISA included members of the families Sphingomonadaceae and
      Cytophagacaceae and the genus Zoogloea. ARISA results indicated an adverse impact
      of SWNTs on the sphingomonad relative to other community members. Changes in
      community structure also occurred in both SWNT-exposed and control reactors over
      the experimental time period and with the date on which activated sludge was
      obtained from a wastewater treatment facility. CONCLUSIONS: These results
      indicate that SWNTs differentially impact members of the activated sludge reactor
      bacterial community. SIGNIFICANCE AND IMPACT OF THE STUDY: The finding that
      community structure was affected by SWNTs indicates that this emerging
      contaminant differentially impacted members of the activated sludge bacterial
      community and raises the concern that SWNTs may also affect the services it
      provides.

PMID- 20809925
TI  - Candida krusei bronchopneumonia with nodular infiltrates in a patient with
      chronic renal failure on haemodialysis--case report and review of literature.

PMID- 20809926
TI  - Abstracts of the 2010 Joint International Neurogastroenterology and Motility
      Meeting. August 26-29, 2010. Boston, Massachusetts, USA.

PMID- 20809927
TI  - Enhanced chloroplast transgene expression in a nuclear mutant of Chlamydomonas.
AB  - Chloroplast transformation in microalgae offers great promise for the production
      of proteins of pharmaceutical interest or for the development of novel biofuels.
      For many applications, high level expression of transgenes is desirable. We have
      transformed the chloroplast of Chlamydomonas reinhardtii with two genes, acrV and
      vapA, which encode antigens from the fish pathogen Aeromonas salmonicida. The
      promoters and 5' untranslated regions of four chloroplast genes were compared for
      their ability to drive expression of the bacterial genes. The highest levels of
      expression were obtained when they were placed under the control of the cis
      acting elements from the psaA-exon1 gene. The expression of these chimeric genes
      was further increased when a nuclear mutation that affects a factor involved in
      psaA splicing was introduced in the genetic background of the chloroplast
      transformants. Accumulation of both the chimeric mRNAs and the recombinant
      proteins was dramatically increased, indicating that negative feedback loops
      limit the expression of chloroplast transgenes. Our results demonstrate the
      potential of manipulating anterograde signalling to alter negative regulatory
      feedback loops in the chloroplast and improve transgene expression.

PMID- 20809928
TI  - Comparative analysis of drought-responsive transcriptome in Indica rice genotypes
      with contrasting drought tolerance.
AB  - Genetic improvement in drought tolerance in rice is the key to save water for
      sustainable agriculture. Drought tolerance is a complex trait and involves
      interplay of a vast array of genes. Several genotypes of rice have evolved
      features that impart tolerance to drought and other abiotic stresses. Comparative
      analysis of drought stress-responsive transcriptome between drought-tolerant (DT)
      landraces/genotypes and drought-sensitive modern rice cultivars will unravel
      novel genetic regulatory mechanisms involved in stress tolerance. Here, we report
      transcriptome analysis in a highly DT rice landrace, Nagina 22 (N22), versus a
      high-yielding but drought-susceptible rice variety IR64. Both genotypes exhibited
      a diverse global transcriptional response under normal and drought conditions.
      Gene ontology (GO) analysis suggested that drought tolerance of N22 was
      attributable to the enhanced expression of several enzyme-encoding genes. Drought
      susceptibility of IR64 was attributable to significant down-regulation of
      regulatory components that confer drought tolerance. Pathway analysis unravelled
      significant up-regulation of several components of carbon fixation,
      glycolysis/gluconeogenesis and flavonoid biosynthesis and down-regulation of
      starch and sucrose metabolism in both the cultivars under drought. However,
      significant up-regulation of alpha-linolenic acid metabolic pathway observed in
      N22 under drought appears to be in good agreement with high drought tolerance of
      this genotype. Consensus cis-motif profiling of drought-induced co-expressed
      genes led to the identification of novel cis-motifs. Taken together, the results
      of the comparative transcriptome analysis led to the identification of specific
      genotype-dependent genes responsible for drought tolerance in the rice landrace
      N22.

PMID- 20809929
TI  - Novel demonstration of RNAi in citrus reveals importance of citrus callose
      synthase in defence against Xanthomonas citri subsp. citri.
AB  - Citrus is an economically important fruit crop that is severely afflicted by
      citrus canker, a disease caused by the bacterial phytopathogen, Xanthomonas citri
      subsp. citri (Xcc). GenBank houses a large collection of Expressed Sequence Tags
      (ESTs) enriched with transcripts generated during the defence response against
      this pathogen; however, there are currently no strategies in citrus to assess the
      function of candidate genes. This has greatly limited research as defence
      signalling genes are often involved in multiple pathways. In this study, we
      demonstrate the efficacy of RNA interference (RNAi) as a functional genomics tool
      to assess the function of candidate genes involved in the defence response of
      Citrus limon against the citrus canker pathogen. Double-stranded RNA expression
      vectors, encoding hairpin RNAs for citrus host genes, were delivered to lemon
      leaves by transient infiltration with transformed Agrobacterium. As proof of
      principle, we have established silencing of citrus phytoene desaturase (PDS) and
      callose synthase (CalS1) genes. Phenotypic and molecular analyses showed that
      silencing vectors were functional not only in lemon plants but also in other
      species of the Rutaceae family. Using silencing of CalS1, we have demonstrated
      that plant cell wall-associated defence is the principal initial barrier against
      Xanthomonas infection in citrus plants. Additionally, we present here results
      that suggest that H2O2 accumulation, which is suppressed by xanthan from Xcc
      during pathogenesis, contributes to inhibition of xanthan-deficient Xcc mutant
      growth either in wild-type or CalS1-silenced plants. With this work, we have
      demonstrated that high-throughput reverse genetic analysis is feasible in citrus.

PMID- 20809930
TI  - The GRONORUN 2 study: effectiveness of a preconditioning program on preventing
      running related injuries in novice runners. The design of a randomized controlled
      trial.
AB  - BACKGROUND: Distance running is a popular recreational exercise. It is a
      beneficial activity for health and well being. However, running may also cause
      injuries, especially of the lower extremities. In literature there is no
      agreement what intrinsic and extrinsic factors cause running related injuries
      (RRIs). In theory, most RRIs are elicited by training errors, this too much, too
      soon. In a preconditioning program runners can adapt more gradually to the high
      mechanical loads of running and will be less susceptible to RRIs. In this study
      the effectiveness of a 4-week preconditioning program on the incidence of RRIs in
      novice runners prior to a training program will be studied. METHODS/DESIGN: The
      GRONORUN 2 (Groningen Novice Running) study is a two arm randomized controlled
      trial studying the effect of a 4-week preconditioning (PRECON) program in a group
      of novice runners. All participants wanted to train for the recreational
      Groningen 4-Mile running event. The PRECON group started a 4-week preconditioning
      program with walking and hopping exercises 4 weeks before the start of the
      training program. The control (CON) and PRECON group started a frequently used 9
      week training program in preparation for the Groningen 4-Mile running
      event.During the follow up period participants registered their running exposure,
      other sporting activities and running related injuries in an Internet based
      running log. The primary outcome measure was the number of RRIs. RRI was defined
      as a musculoskeletal ailment or complaint of the lower extremities or back
      causing a restriction on running for at least three training sessions.
      DISCUSSION: The GRONORUN 2 study will add important information to the existing
      running science. The concept of preconditioning is easy to implement in existing
      training programs and will hopefully prevent RRIs especially in novice runners.
      TRIAL REGISTRATION: The Netherlands National Trial Register NTR1906. The NTR is
      part of the WHO Primary Registries.

PMID- 20809931
TI  - Gene set analysis exploiting the topology of a pathway.
AB  - BACKGROUND: Recently, a great effort in microarray data analysis is directed
      towards the study of the so-called gene sets. A gene set is defined by genes that
      are, somehow, functionally related. For example, genes appearing in a known
      biological pathway naturally define a gene set. The gene sets are usually
      identified from a priori biological knowledge. Nowadays, many bioinformatics
      resources store such kind of knowledge (see, for example, the Kyoto Encyclopedia
      of Genes and Genomes, among others). Although pathways maps carry important
      information about the structure of correlation among genes that should not be
      neglected, the currently available multivariate methods for gene set analysis do
      not fully exploit it. RESULTS: We propose a novel gene set analysis specifically
      designed for gene sets defined by pathways. Such analysis, based on graphical
      models, explicitly incorporates the dependence structure among genes highlighted
      by the topology of pathways. The analysis is designed to be used for overall
      surveillance of changes in a pathway in different experimental conditions. In
      fact, under different circumstances, not only the expression of the genes in a
      pathway, but also the strength of their relations may change. The methods
      resulting from the proposal allow both to test for variations in the strength of
      the links, and to properly account for heteroschedasticity in the usual tests for
      differential expression. CONCLUSIONS: The use of graphical models allows a deeper
      look at the components of the pathway that can be tested separately and compared
      marginally. In this way it is possible to test single components of the pathway
      and highlight only those involved in its deregulation.

PMID- 20809932
TI  - Meis1 specifies positional information in the retina and tectum to organize the
      zebrafish visual system.
AB  - BACKGROUND: During visual system development, multiple signalling pathways
      cooperate to specify axial polarity within the retina and optic tectum. This
      information is required for the topographic mapping of retinal ganglion cell
      axons on the tectum. Meis1 is a TALE-class homeodomain transcription factor known
      to specify anterior-posterior identity in the hindbrain, but its role in visual
      system patterning has not been investigated. RESULTS: meis1 is expressed in both
      the presumptive retina and tectum. An analysis of retinal patterning reveals that
      Meis1 is required to correctly specify both dorsal-ventral and nasal-temporal
      identity in the zebrafish retina. Meis1-knockdown results in a loss of smad1
      expression and an upregulation in follistatin expression, thereby causing lower
      levels of Bmp signalling and a partial ventralization of the retina.
      Additionally, Meis1-deficient embryos exhibit ectopic Fgf signalling in the
      developing retina and a corresponding loss of temporal identity. Meis1 also
      positively regulates ephrin gene expression in the tectum. Consistent with these
      patterning phenotypes, a knockdown of Meis1 ultimately results in retinotectal
      mapping defects. CONCLUSIONS: In this work we describe a novel role for Meis1 in
      regulating Bmp signalling and in specifying temporal identity in the retina. By
      patterning both the retina and tectum, Meis1 plays an important role in
      establishing the retinotectal map and organizing the visual system.

PMID- 20809933
TI  - A systematic investigation of Escherichia coli central carbon metabolism in
      response to superoxide stress.
AB  - BACKGROUND: The cellular responses of bacteria to superoxide stress can be used
      to model adaptation to severe environmental changes. Superoxide stress promotes
      the excessive production of reactive oxygen species (ROS) that have detrimental
      effects on cell metabolic and other physiological activities. To antagonize such
      effects, the cell needs to regulate a range of metabolic reactions in a
      coordinated way, so that coherent metabolic responses are generated by the
      cellular metabolic reaction network as a whole. In the present study, we have
      used a quantitative metabolic flux analysis approach, together with measurement
      of gene expression and activity of key enzymes, to investigate changes in central
      carbon metabolism that occur in Escherichia coli in response to paraquat-induced
      superoxide stress. The cellular regulatory mechanisms involved in the observed
      global flux changes are discussed. RESULTS: Flux analysis based on nuclear
      magnetic resonance (NMR) and mass spectroscopy (MS) measurements and computation
      provided quantitative results on the metabolic fluxes redistribution of the E.
      coli central carbon network under paraquat-induced oxidative stress. The
      metabolic fluxes of the glycolytic pathway were redirected to the pentose
      phosphate pathway (PP pathway). The production of acetate increased
      significantly, the fluxes associated with the TCA cycle decreased, and the fluxes
      in the glyoxylate shunt increased in response to oxidative stress. These global
      flux changes resulted in an increased ratio of NADPH:NADH and in the accumulation
      of alpha-ketoglutarate. CONCLUSIONS: Metabolic flux analysis provided a
      quantitative and global picture of responses of the E. coli central carbon
      metabolic network to oxidative stress. Systematic adjustments of cellular
      physiological state clearly occurred in response to changes in metabolic fluxes
      induced by oxidative stress. Quantitative flux analysis therefore could reveal
      the physiological state of the cell at the systems level and is a useful
      complement to molecular systems approaches, such as proteomics and transcription
      analyses.

PMID- 20809934
TI  - Early detection of COPD in primary care--the Copenhagen COPD Screening Project.
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is among the leading
      causes of death in the world, and further increases in the prevalence and
      mortality are predicted. Delay in diagnosing COPD appears frequently even though
      current consensus guidelines emphasize the importance of early detection of the
      disease. The aim of the present study is to evaluate the effectiveness of a
      screening programme in general practice. METHODS/DESIGN: Subjects aged 65 years
      and older registered with a General Practitioner (GP) in the eastern Copenhagen
      will receive a written invitation and a simple questionnaire focusing on risk
      factors and symptoms of COPD. Subjects who meet the following criteria will be
      encouraged to undergo spirometric testing at their GP: current smokers, former
      smokers, and subjects with no smoking history but who have dyspnea and/or chronic
      cough with sputum. DISCUSSION: The Copenhagen COPD Screening Project evaluates
      the effectiveness of a two-stage screening program for COPD in general practice
      and provides important information on how to organize early detection of COPD in
      general practice in the future.

PMID- 20809935
TI  - The multifaceted role of pirfenidone and its novel targets.
AB  - BACKGROUND: Pirfenidone (PFD) is a molecule that exhibits antifibrotic properties
      in a variety of in vitro and animal models of lung, liver and renal fibrosis.
      These pathologies share many fibrogenic pathways with an abnormal fibrous wound
      healing process; consequently, tissue repair and tissue regeneration-regulating
      mechanisms are altered. OBJECTIVE: To investigate the usefulness of PFD as an
      antifibrotic agent in clinical and experimental models of fibrotic disease.
      CONCLUSIONS: There is a growing understanding of the molecular effects of PFD on
      the wound healing mechanism, leading to novel approaches for the management of
      fibrosis in lung, liver and renal tissues. Although the optimum treatment for
      fibrosis remains undefined, it is possible that combined therapeutic regimens
      that include this wide-application molecule, pirfenidone, could offer a useful
      treatment for fibrotic disease.

PMID- 20809936
TI  - Mast cells and hypoxia drive tissue metaplasia and heterotopic ossification in
      idiopathic arthrofibrosis after total knee arthroplasty.
AB  - BACKGROUND: Idiopathic arthrofibrosis occurs in 3-4% of patients who undergo
      total knee arthroplasty (TKA). However, little is known about the cellular or
      molecular changes involved in the onset or progression of this condition. To
      classify the histomorphologic changes and evaluate potential contributing
      factors, periarticular tissues from the knees of patients with arthrofibrosis
      were analyzed for fibroblast and mast cell proliferation, heterotopic
      ossification, cellular apoptosis, hypoxia and oxidative stress. RESULTS: The
      arthrofibrotic tissue was composed of dense fibroblastic regions, with limited
      vascularity along the outer edges. Within the fibrotic regions, elevated numbers
      of chymase/fibroblast growth factor (FGF)-expressing mast cells were observed. In
      addition, this region contained fibrocartilage and associated heterotopic
      ossification, which quantitatively correlated with decreased range of motion
      (stiffness). Fibrotic, fibrocartilage and ossified regions contained few terminal
      dUTP nick end labeling (TUNEL)-positive or apoptotic cells, despite positive
      immunostaining for lactate dehydrogenase (LDH)5, a marker of hypoxia, and
      nitrotyrosine, a marker for protein nitrosylation. LDH5 and nitrotyrosine were
      found in the same tissue areas, indicating that hypoxic areas within the tissue
      were associated with increased production of reactive oxygen and nitrogen
      species. CONCLUSIONS: Taken together, we suggest that hypoxia-associated
      oxidative stress initiates mast cell proliferation and FGF secretion, spurring
      fibroblast proliferation and tissue fibrosis. Fibroblasts within this hypoxic
      environment undergo metaplastic transformation to fibrocartilage, followed by
      heterotopic ossification, resulting in increased joint stiffness. Thus, hypoxia
      and associated oxidative stress are potential therapeutic targets for fibrosis
      and metaplastic progression of idiopathic arthrofibrosis after TKA.

PMID- 20809938
TI  - Uniform comparison of several drugs which provide protection from noise induced
      hearing loss.
AB  - BACKGROUND: The ability of drugs to reduce noise induced hearing loss (NIHL) has
      been evaluated in diverse experimental conditions (animal species, noise
      intensities, durations, assessment techniques, etc), making it difficult to
      assess their relative efficacy. The present study was designed to provide more
      uniform comparisons and to allow to a better understanding of the mechanism of
      the NIHL. METHODS: The drugs studied included furosemide (loop diuretic) and the
      antioxidants N Acetyl-L-Cysteine, vitamins A, C, E with the vasodilator
      magnesium. Mice were exposed to a continuous broadband noise (113 dB SPL for 3.5
      hours) and the NIHL was assessed in all animals before noise exposure and 1 week
      after with auditory nerve brainstem evoked responses (ABR) to broadband clicks
      and to 8 kHz tone bursts. RESULTS: Each of the drugs alone and in combination led
      to similar reductions in NIHL. CONCLUSIONS: The loop diuretic furosemide, by
      reducing the magnitude of the endocochlear potential in scala media, probably
      depressed active vibrations of the outer hair cells and basilar membrane,
      resulting in reduction of free radical formation during the noise exposure. The
      antioxidants N Acetyl-L-Cysteine and vitamins A, C, E with the vasodilator
      magnesium presumably counteract the free radicals. Thus, the administration of
      the antioxidants to animals in which free radical formation had already been
      reduced by previous injection of furosemide did not have an additional protective
      effect on the NIHL.

PMID- 20809937
TI  - Impact of early psychosocial factors (childhood socioeconomic factors and
      adversities) on future risk of type 2 diabetes, metabolic disturbances and
      obesity: a systematic review.
AB  - BACKGROUND: Psychological factors and socioeconomic status (SES) have a notable
      impact on health disparities, including type 2 diabetes risk. However, the link
      between childhood psychosocial factors, such as childhood adversities or parental
      SES, and metabolic disturbances is less well established. In addition, the
      lifetime perspective including adult socioeconomic factors remains of further
      interest.We carried out a systematic review with the main question if there is
      evidence in population- or community-based studies that childhood adversities
      (like neglect, traumata and deprivation) have considerable impact on type 2
      diabetes incidence and other metabolic disturbances. Also, parental SES was
      included in the search as risk factor for both, diabetes and adverse childhood
      experiences. Finally, we assumed that obesity might be a mediator for the
      association of childhood adversities with diabetes incidence. Therefore, we
      carried out a second review on obesity, applying a similar search strategy.
      METHODS: Two systematic reviews were carried out. Longitudinal, population- or
      community-based studies were included if they contained data on psychosocial
      factors in childhood and either diabetes incidence or obesity risk. RESULTS: We
      included ten studies comprising a total of 200,381 individuals. Eight out of ten
      studies indicated that low parental status was associated with type 2 diabetes
      incidence or the development of metabolic abnormalities. Adjustment for adult SES
      and obesity tended to attenuate the childhood SES-attributable risk but the
      association remained. For obesity, eleven studies were included with a total
      sample size of 70,420 participants. Four out of eleven studies observed an
      independent association of low childhood SES on the risk for overweight and
      obesity later in life. CONCLUSIONS: Taken together, there is evidence that
      childhood SES is associated with type 2 diabetes and obesity in later life. The
      database on the role of psychological factors such as traumata and childhood
      adversities for the future risk of type 2 diabetes or obesity is too small to
      draw conclusions. Thus, more population-based longitudinal studies and
      international standards to assess psychosocial factors are needed to clarify the
      mechanisms leading to the observed health disparities.

PMID- 20809939
TI  - Migration, early axonogenesis, and Reelin-dependent layer-forming behavior of
      early/posterior-born Purkinje cells in the developing mouse lateral cerebellum.
AB  - BACKGROUND: Cerebellar corticogenesis begins with the assembly of Purkinje cells
      into the Purkinje plate (PP) by embryonic day 14.5 (E14.5) in mice. Although the
      dependence of PP formation on the secreted protein Reelin is well known and a
      prevailing model suggests that Purkinje cells migrate along the 'radial glial'
      fibers connecting the ventricular and pial surfaces, it is not clear how Purkinje
      cells behave in response to Reelin to initiate the PP. Furthermore, it is not
      known what nascent Purkinje cells look like in vivo. When and how Purkinje cells
      start axonogenesis must also be elucidated. RESULTS: We show that Purkinje cells
      generated on E10.5 in the posterior periventricular region of the lateral
      cerebellum migrate tangentially, after only transiently migrating radially,
      towards the anterior, exhibiting an elongated morphology consistent with
      axonogenesis at E12.5. After their somata reach the outer/dorsal region by E13.5,
      they change 'posture' by E14.5 through remodeling of non-axon (dendrite-like)
      processes and a switchback-like mode of somal movement towards a superficial
      Reelin-rich zone, while their axon-like fibers remain relatively deep, which
      demarcates the somata-packed portion as a plate. In reeler cerebella, the early
      born posterior lateral Purkinje cells are initially normal during migration with
      anteriorly extended axon-like fibers until E13.5, but then fail to form the PP
      due to lack of the posture-change step. CONCLUSIONS: Previously unknown behaviors
      are revealed for a subset of Purkinje cells born early in the posteior lateral
      cerebellum: tangential migration; early axonogenesis; and Reelin-dependent
      reorientation initiating PP formation. This study provides a solid basis for
      further elucidation of Reelin's function and the mechanisms underlying the
      cerebellar corticogenesis, and will contribute to the understanding of how
      polarization of individual cells drives overall brain morphogenesis.

PMID- 20809940
TI  - The Nordic maintenance care program: what are the indications for maintenance
      care in patients with low back pain? A survey of the members of the Danish
      Chiropractors' Association.
AB  - BACKGROUND: Maintenance care (MC) is relatively commonly used among
      chiropractors. However, factual information is needed on its indications for use.
      OBJECTIVES: This study had two objectives: 1) to describe which role patients'
      past history and treatment outcome play in chiropractors' decision to use MC in
      patients with low back pain, 2) to investigate if the chiropractors'
      clinical/educational background has an effect on the frequency of using MC and
      their indications for use of MC. METHOD: An anonymous questionnaire was sent to
      all 413 chiropractors practising in Denmark. Its main part consisted of 3 sets of
      4 questions relating to one basic case of low back pain. For each case, the
      chiropractors were asked if they would use MC as they self-defined the term
      (no/perhaps/yes). There were questions also on gender, age, educational and
      clinical background, and on the number of MC patients seen by these
      chiropractors. Their decision to recommend MC was reported. Associations between
      the demographic variables and 1) the frequency of MC-use and 2) their indications
      for use of MC were tested through multivariate analysis. RESULTS: The response
      rate was 72%. Non-indications for MC were: 1) a good outcome combined with no
      previous events, or 2) a past history of LBP and gradual worsening with
      treatment. Indications for MC were a good outcome combined with a previous
      history of low back pain between once a month and once a year. The mean
      proportion of MC patients per week were 22% (SD 19), ranging from 0% to 100%. The
      use of MC was highest among experienced chiropractors, those who were educated in
      North America, and clinic owners. However, in Denmark most chiropractors
      graduated before 1999, are educated abroad, whereas most chiropractors thereafter
      are educated in Denmark. Therefore, we cannot conclude whether this difference
      relates to education or years of experience. There were no associations detected
      between demographic variables and the indications for MC. CONCLUSIONS: There is
      relatively high consensus on when MC should and should not be used. A history of
      prior low back pain combined with a positive response to treatment encourages the
      use of MC, whereas no previous history of back pain or a worsening of symptoms
      discourages the use of MC. There seems to be a difference in the proportional use
      of MC between chiropractors with more experience educated in North America and
      those with less experience educated in Denmark.

PMID- 20809941
TI  - Expression of transcription factors snail, slug, and twist in human bladder
      carcinoma.
AB  - BACKGROUND: Slug, snail, and twist are transcription factors that regulate the
      expression of tumor suppressors such as E-cadherin. In this study, we aimed to
      examine the expression of these transcription factors in human bladder carcinoma.
      METHODS: We first investigated expression of slug, snail, twist and E-cadherin in
      five bladder Carcinoma cell lines by reverse transcription-polymerase chain
      reaction and western blotting. Furthermore, we investigated slug, snail, and
      twist and E-cadherin expression by immunohistochemistry with bladder carcinoma
      (tumor, n = 120; background, n = 42). RESULTS: Expression of slug mRNA and
      protein was detected in all cell lines, twist was clearly expressed in two out of
      five bladder carcinoma cell lines, snail was not expressed, and E-cadherin was
      detected in 3 cell lines. 44.2% (53/120) of human bladder carcinoma tissues and
      38% (16/42) background tissue showed an expression of twist; 62.5% (75/120) of
      human bladder carcinoma tissues and 40% (17/42) background tissue showed an
      expression of slug, 15.8% (19/120) of human bladder carcinoma tissues and 76%
      (32/42) background tissue showed an expression of snail, and 25.8% (31/120) cases
      were negative for E-cadherin expression in carcinoma tissues. Expression of slug
      and twist shows increased levels in tumors, whereas snail seems reduced.
      Statistically significant correlations were found between twist, slug, and E
      cadherin expression. Immunohistochemistry analysis showed that twist was elevated
      with increasing tumor stage (P = 0.001), the grade (P < 0.001), the progression
      (P = 0.035). Slug was elevated and snail was reduced with increasing nodal
      involvement (tumor-node-metastasis status) (P = 0.004, P = 0.01). E-cadherin was
      reduced in expression corresponding with tumor grade (P < 0.01). Positive twist,
      slug and E-cadherin expression clearly predicted poorer PFS (P = 0.042, P =
      0.014, P = 0.001). In the multivariate analysis, only snail and E-cadherin
      expression were independent prognostic factors for OS (P = 0.002, P < 0.001).
      CONCLUSIONS: These data demonstrate that twist, snail and slug have inappropriate
      expression in bladder carcinoma and that this may play a part in the progression
      of human bladder carcinoma.

PMID- 20809942
TI  - Can the Non-pneumatic Anti-Shock Garment (NASG) reduce adverse maternal outcomes
      from postpartum hemorrhage? Evidence from Egypt and Nigeria.
AB  - BACKGROUND: Postpartum hemorrhage (PPH) is the leading cause of maternal
      mortality and severe maternal morbidity. The Non-pneumatic Anti-Shock Garment
      (NASG), a first-aid lower-body compression device, may decrease adverse outcomes
      from obstetric hemorrhage. This article is the first to report the effect of the
      NASG for PPH. METHODS: This pre-intervention/NASG study of 854 women was
      conducted in four referral facilities in Nigeria and two in Egypt between 2004
      2008. Entry criteria were women with PPH due to uterine atony, retained placenta,
      ruptured uterus, vaginal or cervical lacerations or placenta accreta with
      estimated blood loss of >= 750 mL and one clinical sign of shock. Differences in
      demographics, conditions on study entry, treatment and outcomes were examined.
      The Wilcoxon rank-sum test and relative risks with 95% confidence intervals were
      calculated for primary outcomes - measured blood loss, emergency hysterectomy,
      mortality, morbidity (each individually), and a combined variable, "adverse
      outcomes", defined as severe morbidity and mortality. A multiple logistic
      regression model was fitted to test the independent association between the NASG
      and the combined severe morbidity and mortality outcome. RESULTS: Measured blood
      loss decreased by 50% between phases; women experienced 400 mL of median blood
      loss after study entry in the pre-intervention and 200 mL in the NASG phase (p <
      0.0001). As individual outcomes, mortality decreased from 9% pre-intervention to
      3.1% in the NASG phase (RR 0.35, 95% CI 0.19-0.62); severe morbidity decreased
      from 4.2% to 1%, in the NASG phase (RR 0.24, 95% CI 0.09-0.67). As a combination,
      "adverse outcomes," decreased from 12.8% to 4.1% in the NASG phase (RR 0.32, 95%
      CI 0.19-0.53). In a multiple logistic regression model, the NASG was associated
      with the combined outcome of severe maternal morbidity and mortality (OR 0.42,
      95% CI 0.18-0.99). CONCLUSION: In this non-randomized study, in which bias is
      inherent, the NASG showed promise for reducing blood loss, emergency
      hysterectomy, morbidity and mortality associated with PPH in referral facilities
      in Egypt and Nigeria.

PMID- 20809943
TI  - Incidence of sexual dysfunction: a prospective survey in Ghanaian females.
AB  - BACKGROUND: Sexuality is a complex phenomenon that is being influenced by
      psychological as well as physiological factors. Its dysfunction includes desire,
      arousal, orgasmic and sex pain disorders. The present study aimed to assess the
      incidence of sexual dysfunction (SD) and related risk factors in a cohort of
      Ghanaian women. METHOD: The Golombok Rust Inventory of Sexual Satisfaction
      (GRISS) was administered to 400 healthy women between 18 and 58 years old (mean
      +/- SD: 30.1 +/- 7.9) domiciled in the Kumasi metropolis. RESULTS: The response
      rate was 75.3% after 99 were excluded. Of the remaining 301 women, 50% were
      engaged in exercise, 26.7% indulge in alcoholic beverages and only 2% were
      smokers. A total of 62.1% of the women had attained high education, whilst, 28.9%
      were married. After logistic regression analysis, alcohol emerged (OR: 2.0; CI:
      1.0 - 3.8; p = 0.04) as the main risk factor for SD. The overall prevalence of SD
      in these subjects was 72.8%. Severe difficulties with sexual function were
      identified in 3.3% of the studied population. The most prevalent areas of
      difficulty were anorgasmia (72.4%), sexual infrequency (71.4%), dissatisfaction
      (77.7%), vaginismus (68.1%), avoidance of sexual intercourse (62.5%), non
      sensuality (61.5%) and non-communication (54.2%). Whereas 8% had severe
      difficulties with anorgasmia, only 6% had severe difficulties with vaginismus.
      CONCLUSION: SD affects more than 70% of Ghanaian women who are sexually active.
      Alcohol significantly influences sexual activity.

PMID- 20809944
TI  - Effectiveness of BCG vaccination to aged mice.
AB  - BACKGROUND: The tuberculosis (TB) still increases in the number of new cases,
      which is estimated to approach 10 million in 2010. The number of aged people has
      been growing all over the world. Ageing is one of risk factors in tuberculosis
      because of decreased immune responses in aged people. Mycobacterium bovis
      Bacillus Calmette Guerin (BCG) is a sole vaccine currently used for TB, however,
      the efficacy of BCG in adults is still a matter of debate. Emerging the multidrug
      resistant Mycobacterium tuberculosis (MDR-TB) make us to see the importance of
      vaccination against TB in new light. In this study, we evaluated the efficacy of
      BCG vaccination in aged mice. RESULTS: The Th1 responses, interferon-gamma
      production and interleukin 2, in BCG inoculated aged mice (24-month-old) were
      comparable to those of young mice (4- to 6-week-old). The protection activity of
      BCG in aged mice against Mycobacterium tuberculosis H37Rv was also the same as
      young mice. CONCLUSION: These findings suggest that vaccination in aged
      generation is still effective for protection against tuberculosis.

PMID- 20809945
TI  - School wellbeing among children in grades 1-10.
AB  - BACKGROUND: Determinants of children's school wellbeing have not been extensively
      studied. In this cross-sectional study of school children we assessed how factors
      assumed to promote wellbeing and factors assumed to adversely influence wellbeing
      were associated with self-reported wellbeing in school. METHODS: Children from
      five schools, 230 boys and 189 girls in grades 1-10, responded to the same set of
      questions. We used proportional odds logistic regression to assess the
      associations of promoting and restraining factors with school wellbeing. RESULTS:
      In a multivariable analysis, degree of school wellbeing in boys was strongly and
      positively related to enjoying school work (odds ratio, 3.84, 95% CI 2.38 to
      6.22) and receiving necessary help (odds ratio, 3.55, 95% CI 2.17 to 5.80) from
      teachers. In girls, being bothered during lessons was strongly and negatively
      associated with school wellbeing (odds ratio, 0.43, 95% CI 0.22 to 0.85).
      CONCLUSIONS: Different factors may determine school wellbeing in boys and girls,
      but for both genders, factors relevant for lessons may be more important than
      factors related to recess. Especially in boys, the student-teacher relationship
      may be of particular importance.

PMID- 20809946
TI  - Use of fuzzy edge single-photon emission computed tomography analysis in definite
      Alzheimer's disease--a retrospective study.
AB  - BACKGROUND: Definite Alzheimer's disease (AD) requires neuropathological
      confirmation. Single-photon emission computed tomography (SPECT) may enhance
      diagnostic accuracy, but due to restricted sensitivity and specificity, the role
      of SPECT is largely limited with regard to this purpose. METHODS: We propose a
      new method of SPECT data analysis. The method is based on a combination of
      parietal lobe selection (as regions-of-interest (ROI)), 3D fuzzy edge detection,
      and 3D watershed transformation. We applied the algorithm to three-dimensional
      SPECT images of human brains and compared the number of watershed regions inside
      the ROI between AD patients and controls. The Student's two-sample t-test was
      used for testing domain number equity in both groups. RESULTS: AD patients had a
      significantly reduced number of watershed regions compared to controls (p <
      0.01). A sensitivity of 94.1% and specificity of 80% was obtained with a
      threshold value of 57.11 for the watershed domain number. The narrowing of the
      SPECT analysis to parietal regions leads to a substantial increase in both
      sensitivity and specificity. CONCLUSIONS: Our non-invasive, relatively low-cost,
      and easy method can contribute to a more precise diagnosis of AD.

PMID- 20809947
TI  - African signatures of recent positive selection in human FOXI1.
AB  - BACKGROUND: The human FOXI1 gene codes for a transcription factor involved in the
      physiology of the inner ear, testis, and kidney. Using three interspecies
      comparisons, it has been suggested that this may be a gene under human-specific
      selection. We sought to confirm this finding by using an extended set of
      orthologous sequences. Additionally, we explored for signals of natural selection
      within humans by sequencing the gene in 20 Europeans, 20 East Asians and 20
      Yorubas and by analysing SNP variation in a 2 Mb region centered on FOXI1 in 39
      worldwide human populations from the HGDP-CEPH diversity panel. RESULTS: The
      genome sequences recently available from other primate and non-primate species
      showed that FOXI1 divergence patterns are compatible with neutral evolution.
      Sequence-based neutrality tests were not significant in Europeans, East Asians or
      Yorubas. However, the Long Range Haplotype (LRH) test, as well as the iHS and XP
      Rsb statistics revealed significantly extended tracks of homozygosity around
      FOXI1 in Africa, suggesting a recent episode of positive selection acting on this
      gene. A functionally relevant SNP, as well as several SNPs either on the
      putatively selected core haplotypes or with significant iHS or XP-Rsb values,
      displayed allele frequencies strongly correlated with the absolute geographical
      latitude of the populations sampled. CONCLUSIONS: We present evidence for recent
      positive selection in the FOXI1 gene region in Africa. Climate might be related
      to this recent adaptive event in humans. Of the multiple functions of FOXI1, its
      role in kidney-mediated water-electrolyte homeostasis is the most obvious
      candidate for explaining a climate-related adaptation.

PMID- 20809948
TI  - Genetic divergence of influenza A NS1 gene in pandemic 2009 H1N1 isolates with
      respect to H1N1 and H3N2 isolates from previous seasonal epidemics.
AB  - BACKGROUND: The Influenza A pandemic sustained by a new H1N1 variant (H1N1v)
      started in Mexico and the USA at the end of April 2009 spreading worldwide in a
      few weeks. In this study we investigate the variability of the NS1 gene of the
      pandemic H1N1v strain with respect to previous seasonal strains circulating in
      humans and the potential selection of virus variants through isolation in cell
      culture. METHODS: During the period April 27th 2009-Jan 15th 2010, 1633 potential
      2009 H1N1v cases have been screened at our center using the CDC detection and
      typing realtime RT-PCR assays. Virus isolation on MDCK cells was systematically
      performed in 1/10 positive cases. A subset of 51 H1N1v strains isolated in the
      period May-September 2009 was selected for NS1 gene sequencing. In addition, 15
      H1N1 and 47 H3N2 virus isolates from three previous seasonal epidemics (2006
      2009) were analyzed in parallel. RESULTS: A low variability in the NS1 amino acid
      (aa) sequence among H1N1v isolates was shown (aa identity 99.5%). A slightly
      higher NS1 variability was observed among H1N1 and H3N2 strains from previous
      epidemics (aa identity 98.6% and 98.9%, respectively). The H1N1v strains were
      closely related (aa identity 92.1%) to swine reference strain
      (A/swine/Oklahoma/042169/2008). In contrast, substantial divergence (aa identity
      83.4%) with respect to human reference strain A/Brevig Mission/1/1918 and
      previous epidemic strains H1N1 and H3N2 (aa identity 78.9% and 77.6%,
      respectively) was shown. Specific sequence signatures of uncertain significance
      in the new virus variant were a C-terminus deletion and a T215P substitution.
      CONCLUSIONS: The H1N1v NS1 gene was more conserved than that of previous epidemic
      strains. In addition, a closer genetic identity of H1N1v with the swine than the
      human reference strains was shown. Hot-spots were shown in the H1N1v NS1 aa
      sequence whose biologic relevance remains to be investigated.

PMID- 20809949
TI  - Intracellular molecular effects of insulin resistance in patients with metabolic
      syndrome.
AB  - AIM OF THE STUDY: Patients with metabolic syndrome (MetS) have an increased risk
      of cardiovascular disease. Data obtained from muscle biopsies have demonstrated
      altered insulin signaling (IS) in patients with MetS. The IS regulates critical
      cell functions including molecular-regulated cellular metabolite fluxes, protein
      and energetic metabolism, cell proliferation and apoptosis with consequent
      regulation of cell life including endothelial homeostasis and blood coagulation.
      However, little is known about blood cell IS in MetS patients. The aim of this
      study was to develop a method to evaluate IS in peripheral lymphocytes to
      identify altered intracellular molecules in patients with MetS to use as risk
      biomarkers of vascular thrombosis. PATIENTS AND METHODS: We investigated 40
      patients with MetS and 20 controls. MetS was defined according to guidelines from
      the US National Cholesterol Education Program Adult Treatment Panel III. Blood
      samples were taken from all participants. Total mononuclear cells were isolated
      from peripheral blood using density gradient centrifugation. IS molecules were
      evaluated using Western blot analysis followed by computer-assisted densitometer
      evaluation. RESULTS: Lymphocytes of MetS patients showed a reduced mTOR
      expression (the mammalian target of rapamycin) which is a fundamental molecule of
      IS. Major impairment of IS was confirmed by reduced upstream and downstream mTOR
      molecules which regulate fundamental cells metabolic functions. CONCLUSIONS: In
      patients with MetS, we found a reduction of mTOR and other mTOR-related molecules
      involved in insulin resistance, cell repair, coagulation and vasculogenesis. A
      reduced expression of mTOR may reflect an increased risk of vascular thrombosis.

PMID- 20809950
TI  - The anxious wait: assessing the impact of patient accessible EHRs for breast
      cancer patients.
AB  - BACKGROUND: Personal health records (PHRs) provide patients with access to
      personal health information (PHI) and targeted education. The use of PHRs has the
      potential to improve a wide range of outcomes, including empowering patients to
      be more active participants in their care. There are a number of widespread
      barriers to adoption, including privacy and security considerations. In addition,
      there are clinical concerns that patients could become anxious or distressed when
      accessing complex medical information. This study assesses the implementation of
      a PHR, and its impact on anxiety levels and perceptions of self-efficacy in a
      sample of breast cancer patients. METHODS: A quasi-experimental pre-test/post
      test design was used to collect data from participants to evaluate the use of the
      PHR. Study participants completed background and pre-assessment questionnaires
      and were then registered into the portal. By entering an activation key,
      participants were then able to review their lab results and diagnostic imaging
      reports. After six weeks, participants completed post-assessment questionnaires
      and usability heuristics. All data were collected using an online survey tool.
      Data were cleaned and analyzed using SAS v9.1. RESULTS: A total of 311 breast
      cancer patients completed demographic and pre-assessment questionnaires, 250
      registered to use the online intervention, and 125 participants completed all
      required study elements. Matching the pre- and post-anxiety scores demonstrated a
      decrease in mean anxiety scores (-2.2, p = 0.03); the chemotherapy sub-group had
      a statistically insignificant mean increase (1.8, p = .14). There was no mean
      change in self-efficacy scores. CONCLUSIONS: Participants generally found the
      portal easy to use; however, the perceived value of improved participation was
      not detected in the self-efficacy scores. Having access to personal health
      information did not increase anxiety levels. While these results suggest that the
      use of this PHR may be of benefit for informing patients, further research is
      required to investigate the impact on the patients experiences, their
      participation in their care, their relationships with the health care team, and
      their health outcomes.

PMID- 20809951
TI  - Determinants of the number of antenatal visits in a metropolitan region.
AB  - BACKGROUND: Antenatal care has a positive effect on pregnancy, both clinically
      and psychologically, but consensus about the optimal number of antenatal visits
      is lacking. This study aims to provide insight into the dynamics of the number of
      antenatal visits a woman receives. Independent effects of predisposing, enabling
      and pregnancy-related determinants are examined. METHODS: Women were recruited in
      nine clinical centres in the Brussels Metropolitan region. Antenatal care use was
      measured prospectively. A Poisson regression model was applied to measure the
      independent effect of individual determinants on the number of antenatal visits.
      RESULTS: Data on antenatal care trajectories in 333 women were collected. The
      multivariate analyses showed that women with a Maghreb or Turkish origin had 14%
      fewer visits compared with European (EU15) women. More highly educated women had
      22% more visits compared with those with a low education. Women with a high
      income had 14% more antenatal visits compared with those with a low income. Fewer
      antenatal visits were observed in multiparae (15%), women initiating care after
      14 weeks of gestation (31%), women without medical risks during the pregnancy
      (12%) and in women with a continuity of care index of 50% or more (12%). More
      visits were observed in delivering after week 37 (22% increase). CONCLUSIONS:
      Predisposing and enabling factors have to be considered when antenatal care
      programmes are evaluated in a metropolitan area. Variations in the number of
      antenatal visits show that socially vulnerable women are more at risk of having
      fewer visits.

PMID- 20809952
TI  - Protocol for a population-based ankylosing spondylitis (PAS) cohort in Wales.
AB  - BACKGROUND: To develop a population-based cohort of people with ankylosing
      spondylitis (AS) in Wales using (1) secondary care clinical datasets, (2) patient
      derived questionnaire data and (3) routinely-collected information in order to
      examine disease history and the health economic cost of AS. METHODS: This data
      model will include and link (1) secondary care clinician datasets (i.e.
      electronic patient notes from the rheumatologist) (2) patient completed
      questionnaires (giving information on disease activity, medication, function,
      quality of life, work limitations and health service utilisation) and (3) a broad
      range of routinely collected data (including; GP records, in-patient hospital
      admission data, emergency department data, laboratory/pathology data and social
      services databases). The protocol involves the use of a unique and powerful data
      linkage system which allows datasets to be interlinked and to complement each
      other. DISCUSSION: This cohort can integrate patient supplied, primary and
      secondary care data into a unified data model. This can be used to study a range
      of issues such as; the true economic costs to the health care system and the
      patient, factors associated with the development of severe disease, long term
      adverse events of new and existing medication and to understand the disease
      history of this condition. It will benefit patients, clinicians and health care
      managers. This study forms a pilot project for the use of routine data/patient
      data linked cohorts for other chronic conditions.

PMID- 20809953
TI  - A randomized controlled trial of telemonitoring in older adults with multiple
      chronic conditions: the Tele-ERA study.
AB  - BACKGROUND: Older adults with multiple chronic illnesses are at risk for
      worsening functional and medical status and hospitalization. Home telemonitoring
      may help slow this decline. This protocol of a randomized controlled trial was
      designed to help determine the impact of home telemonitoring on hospitalization.
      The specific aim of the study reads as follows: to determine the effectiveness of
      home telemonitoring compared with usual care in reducing the combined outcomes of
      hospitalization and emergency department visits in an at-risk population 60 years
      of age or older. METHODS/DESIGN: Two-hundred patients with the highest 10% Mayo
      Clinic Elder Risk Assessment scores will be randomly assigned to one of two
      interventions. Home telemonitoring involves the use of a computer device, the
      Intel Health Guide, which records biometric and symptom data from patients in
      their homes. This information is monitored by midlevel providers associated with
      a primary care medical practice. Under the usual care scenario, patients make
      appointments with their providers as problems arise and use ongoing support such
      as a 24-hour nurse line.Patients will have initial evaluations of gait and
      quality of life using instruments such as the SF-12 Health Survey, the Kokmen
      Short Test of Mental Status, and the PHQ-9 health questionnaire. Patients will be
      followed for 1 year for primary outcomes of hospitalizations and emergency
      department visits. Secondary analysis will include quality of life, compliance
      with the device, and attitudes about telemonitoring. Sample size is based on an
      80% power to detect a 36% difference between the two groups. The primary analysis
      will involve Cox proportional time-to-event analysis. Secondary analysis will use
      t-test comparisons for continuous variables and the chi square test for
      proportional analysis. DISCUSSION: Patients randomized to home telemonitoring
      will have daily assessments of their health status using the device. Registered
      nurse monitoring will assess any change in status followed by videoconferencing
      by a mid-level provider. We obtained trial registration and Institutional Review
      Board approval. TRIAL REGISTRATION: Trial registration number through
      http://www.clinicaltrials.gov: NCT01056640.

PMID- 20809955
TI  - Amyotrophic lateral sclerosis-motor neuron disease, monoclonal gammopathy,
      hyperparathyroidism, and B12 deficiency: case report and review of the
      literature.
AB  - INTRODUCTION: Amyotrophic lateral sclerosis (the most common form of motor neuron
      disease) is a progressive and devastating disease involving both lower and upper
      motor neurons, typically following a relentless path towards death. Given the
      gravity of this diagnosis, all efforts must be made by the clinician to exclude
      alternative and more treatable entities. Frequent serology testing involves
      searching for treatable disorders, including vitamin B12 deficiency, parathyroid
      anomalies, and monoclonal gammopathies. CASE PRESENTATION: We present the case of
      a 78-year-old Caucasian man with all three of the aforementioned commonly
      searched for disorders during an investigation for amyotrophic lateral sclerosis.
      CONCLUSIONS: The clinical utility of these common tests and what they ultimately
      mean in patients with amyotrophic lateral sclerosis is discussed, along with a
      review of the literature.

PMID- 20809954
TI  - Enrichment and differential targeting of complexins 3 and 4 in ribbon-containing
      sensory neurons during zebrafish development.
AB  - BACKGROUND: In sensory systems with broad bandwidths, polarized receptor cells
      utilize highly specialized organelles in their apical and basolateral
      compartments to transduce and ultimately transmit signals to the rest of the
      nervous system. While progress has been made in elucidating the assembly of the
      transduction apparatus, the development of synaptic ribbon-containing terminals
      remains poorly understood. To begin to delineate the targeting of the exocytotic
      machinery specifically in ribbon-containing neurons, we have examined the
      expression of complexins 3 and 4 in the zebrafish visual and acousticolateral
      systems during the first week of development. RESULTS: We have identified five
      members of the complexin 3/4 subfamily in zebrafish that show 50 to 75% amino
      acid identity with mammalian complexins 3 and 4. Utilizing a polyclonal antibody
      that recognizes all five orthologs, we demonstrate that these proteins are
      enriched in ribbon-containing sensory neurons. Complexin 3/4 is rapidly targeted
      to presynaptic terminals in the pineal organ and retina concomitantly with RIBEYE
      b, a component of ribbons. In hair cells of the inner ear and lateral line,
      however, complexin 3/4 immunoreactivity clusters on the apical surfaces of hair
      cells, among their stereocilia, rather than along the basolateral plasma membrane
      with RIBEYE b. A complexin 4a-specific antibody selectively labels the
      presynaptic terminals of visual system ribbon-containing neurons. CONCLUSIONS:
      These results provide evidence for the concurrent transport and/or assembly of
      multiple components of the active zone in developing ribbon terminals. Members of
      the complexin 3/4 subfamily are enriched in these terminals in the visual system
      and in hair bundles of the acousticolateral system, suggesting that these
      proteins are differentially targeted and may have multiple roles in ribbon
      containing sensory neurons.

PMID- 20809956
TI  - Prognostic relevance of Bmi-1 expression and autoantibodies in esophageal
      squamous cell carcinoma.
AB  - BACKGROUND: Overexpression of Bmi-1 has been observed in a variety of cancers,
      and it has been suggested to be an independent prognostic marker for the
      patients. The objective of this study was to determine the level of Bmi-1
      expression or its autoantibodies in human esophageal squamous cell carcinoma
      (ESCC) and to correlate it with clinicopathologic data. METHODS: We first
      examined Bmi-1 expression in ESCC cell lines and tumor samples by RT-PCR and
      Western blot analysis. We then analyzed Bmi-1 protein expression in 171
      clinicopathologically characterized ESCC cases by immunohistochemistry. In
      addition, we detected its autoantibodies in sera of patients with ESCC by ELISA.
      RESULTS: We found that Bmi-1 expression was higher in the immortalized cells,
      cancer cell lines and most cancer tissue than in non-tumorous control tissue at
      both mRNA and protein level. In addition, Bmi-1 expression was observed in 64.3%
      (110 of 171) archive ESCC specimen by immunohistochemistry analysis, and the
      location of Bmi-1 in ESCC was in the nuclei instead of cytoplasm of tumor cells.
      There was a significant difference of Bmi-1 expression in patients categorized
      according to stage (P = 0.003) and pN classification (P = 0.047). Multivariate
      analysis suggested that Bmi-1 expression was an independent prognostic marker for
      ESCC patients. A prognostic significance of Bmi-1 was also found in the subgroup
      of T3~T4 and N1 tumor classification. Bmi-1 autoantibodies were detected in sera
      of 39.0% (62 of 159) ESCC patients. The correlations between anti-Bmi-1
      antibodies and tumor stage (P = 0.040), or lymph node status (P < 0.001) were
      significant. CONCLUSIONS: Our results suggest that Bmi-1 protein is a valuable
      marker of ESCC progression. The presence of Bmi-1 autoantibodies in sera from
      patients with ESCC may have clinical utility in esophageal cancer diagnosis.

PMID- 20809957
TI  - Maternal substance use and integrated treatment programs for women with substance
      abuse issues and their children: a meta-analysis.
AB  - BACKGROUND: The rate of women with substance abuse issues is increasing. Women
      present with a unique constellation of risk factors and presenting needs, which
      may include specific needs in their role as mothers. Numerous integrated programs
      (those with substance use treatment and pregnancy, parenting, or child services)
      have been developed to specifically meet the needs of pregnant and parenting
      women with substance abuse issues. This synthesis and meta-analysis reviews
      research in this important and growing area of treatment. METHODS: We searched
      PsycINFO, MedLine, PubMed, Web of Science, EMBASE, Proquest Dissertations,
      Sociological Abstracts, and CINAHL and compiled a database of 21 studies (2
      randomized trials, 9 quasi-experimental studies, 10 cohort studies) of integrated
      programs published between 1990 and 2007 with outcome data on maternal substance
      use. Data were summarized and where possible, meta-analyses were performed, using
      standardized mean differences (d) effect size estimates. RESULTS: In the two
      studies comparing integrated programs to no treatment, effect sizes for urine
      toxicology and percent using substances significantly favored integrated programs
      and ranged from 0.18 to 1.41. Studies examining changes in maternal substance use
      from beginning to end of treatment were statistically significant and medium
      sized. More specifically, in the five studies measuring severity of drug and
      alcohol use, the average effect sizes were 0.64 and 0.40, respectively. In the
      four cohort studies of days of use, the average effect size was 0.52. Of studies
      comparing integrated to non-integrated programs, four studies assessed urine
      toxicology and two assessed self-reported abstinence. Overall effect sizes for
      each measure were not statistically significant (d = -0.09 and 0.22,
      respectively). CONCLUSIONS: Findings suggest that integrated programs are
      effective in reducing maternal substance use. However, integrated programs were
      not significantly more effective than non-integrated programs. Policy
      implications are discussed with specific attention to the need for funding of
      high quality randomized control trials and improved reporting practices.

PMID- 20809958
TI  - Cross-reactions between engineered xylose and galactose pathways in recombinant
      Saccharomyces cerevisiae.
AB  - BACKGROUND: Overexpression of the PGM2 gene encoding phosphoglucomutase (Pgm2p)
      has been shown to improve galactose utilization both under aerobic and under
      anaerobic conditions. Similarly, xylose utilization has been improved by
      overexpression of genes encoding xylulokinase (XK), enzymes from the non
      oxidative pentose phosphate pathway (non-ox PPP) and deletion of the endogenous
      aldose reductase GRE3 gene in engineered Saccharomyces cerevisiae strains
      carrying either fungal or bacterial xylose pathways. In the present study, we
      investigated how the combination of these traits affect xylose and galactose
      utilization in the presence or absence of glucose in S. cerevisiae strains
      engineered with the xylose reductase (XR)-xylitol dehydrogenase (XDH) pathway.
      RESULTS: In the absence of PGM2 overexpression, the combined overexpression of
      XK, the non-ox PPP and deletion of the GRE3 gene significantly delayed aerobic
      growth on galactose, whereas no difference was observed between the control
      strain and the xylose-engineered strain when the PGM2 gene was overexpressed.
      Under anaerobic conditions, the overexpression of the PGM2 gene increased the
      ethanol yield and the xylose consumption rate in medium containing xylose as the
      only carbon source. The possibility of Pgm2p acting as a xylose isomerase (XI)
      could be excluded by measuring the XI activity in both strains. The additional
      copy of the PGM2 gene also resulted in a shorter fermentation time during the co
      consumption of galactose and xylose. However, the effect was lost upon addition
      of glucose to the growth medium. CONCLUSIONS: PGM2 overexpression was shown to
      benefit xylose and galactose fermentation, alone and in combination. In contrast,
      galactose fermentation was impaired in the engineered xylose-utilizing strain
      harbouring extra copies of the non-ox PPP genes and a deletion of the GRE3 gene,
      unless PGM2 was overexpressed. These cross-reactions are of particular relevance
      for the fermentation of mixed sugars from lignocellulosic feedstock.

PMID- 20809960
TI  - Successful reduction of intraventricular asynchrony is associated with superior
      response to cardiac resynchronization therapy.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is generally associated with
      a low to moderate increase of the left ventricular ejection fraction (LVEF). In
      some patients, however, LVEF improves remarkably and reaches near-normal values.
      The aim of the present study was to further characterize these so called 'super
      responders' with a special focus on the extent of intra- and interventricular
      asynchrony before and after device implantation compared to average responders.
      METHODS: 37 consecutive patients who underwent CRT device implantation according
      to current guidelines were included in the study. Patients were examined by
      echocardiography before, one day after and six months after device implantation.
      Pre-defined criterion for superior response to CRT was an LVEF increase > 15%
      after six months. RESULTS: At follow-up, eight patients (21.6%) were identified
      as super-responders. There were no significant differences regarding age, gender,
      prevalence of ischemic heart disease and LVEF between average and super
      responders at baseline. After six months, LVEF had significantly increased from
      26.7% +/- 5.7% to 33.1% +/- 7.9% (p < 0.001) in average and from 24.0% +/- 6.7%
      to 50.3% +/- 7.4% (p < 0.001) in super-responders. Both groups showed a
      significant reduction of QRS duration as well as LV end-diastolic and -systolic
      volumes under CRT. At baseline, the interventricular mechanical delay (IVMD) was
      53.7 +/- 20.9 ms in average and 56.9 +/- 22.4 ms in super-responders -
      representing a similar extent of interventricular asynchrony in both groups (p =
      0.713). CRT significantly reduced the IVMD to 20.3 +/- 15.7 (p < 0.001) in
      average and to 19.8 +/- 15.9 ms (p = 0.013) in super-responders with no
      difference between both groups (p = 0.858). As a marker for intraventricular
      asynchrony, we assessed the longest intraventricular delay between six basal LV
      segments. At baseline, there was no difference between average (86.2 +/- 30.5 ms)
      and super-responders (78.8 +/- 23.6 ms, p = 0.528). CRT significantly reduced the
      longest intraventricular delay in both groups--with a significant difference
      between average (66.2 +/- 36.2 ms) and super-responders (32.5 +/- 18.3 ms, p =
      0.022). Multivariate logistic regression analysis identified the longest
      intraventricular delay one day after device implantation as an independent
      predictor of superior response to CRT (p = 0.038). CONCLUSIONS: A significant
      reduction of the longest intraventricular delay correlates with superior response
      to CRT.

PMID- 20809959
TI  - MRP3: a molecular target for human glioblastoma multiforme immunotherapy.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) is refractory to conventional
      therapies. To overcome the problem of heterogeneity, more brain tumor markers are
      required for prognosis and targeted therapy. We have identified and validated a
      promising molecular therapeutic target that is expressed by GBM: human multidrug
      resistance protein 3 (MRP3). METHODS: We investigated MRP3 by genetic and
      immunohistochemical (IHC) analysis of human gliomas to determine the incidence,
      distribution, and localization of MRP3 antigens in GBM and their potential
      correlation with survival. To determine MRP3 mRNA transcript and protein
      expression levels, we performed quantitative RT-PCR, raising MRP3-specific
      antibodies, and IHC analysis with biopsies of newly diagnosed GBM patients. We
      used univariate and multivariate analyses to assess the correlation of RNA
      expression and IHC of MRP3 with patient survival, with and without adjustment for
      age, extent of resection, and KPS. RESULTS: Real-time PCR results from 67 GBM
      biopsies indicated that 59/67 (88%) samples highly expressed MRP3 mRNA
      transcripts, in contrast with minimal expression in normal brain samples. Rabbit
      polyvalent and murine monoclonal antibodies generated against an extracellular
      span of MRP3 protein demonstrated reactivity with defined MRP3-expressing cell
      lines and GBM patient biopsies by Western blotting and FACS analyses, the latter
      establishing cell surface MRP3 protein expression. IHC evaluation of 46 GBM
      biopsy samples with anti-MRP3 IgG revealed MRP3 in a primarily membranous and
      cytoplasmic pattern in 42 (91%) of the 46 samples. Relative RNA expression was a
      strong predictor of survival for newly diagnosed GBM patients. Hazard of death
      for GBM patients with high levels of MRP3 RNA expression was 2.71 (95% CI: 1.54
      4.80) times that of patients with low/moderate levels (p = 0.002). CONCLUSIONS:
      Human GBMs overexpress MRP3 at both mRNA and protein levels, and elevated MRP3
      mRNA levels in GBM biopsy samples correlated with a higher risk of death. These
      data suggest that the tumor-associated antigen MRP3 has potential use for
      prognosis and as a target for malignant glioma immunotherapy.

PMID- 20809961
TI  - Validation and use of microdialysis for determination of pharmacokinetic
      properties of the chemotherapeutic agent mitomycin C - an experimental study.
AB  - BACKGROUND: Mitomycin C is a chemotherapeutic agent used in the treatment of
      peritoneal surface malignancies, administered as hyperthermic intraperitoneal
      chemotherapy after cytoreductive surgery. Pharmacokinetic studies have been based
      on analyses of blood, urine and abdominal perfusate, but actual tissue
      concentrations of the drug have never been determined. Microdialysis is an
      established method for continuous monitoring of low-molecular substances in
      tissues, and in the present study microdialysis of mitomycin C was studied in
      vitro and in vivo. METHODS: Using in vitro microdialysis, relative recovery was
      determined when varying drug concentration, temperature and perfusion flow rate.
      In vivo microdialysis was performed in rats to verify long-term stability of
      relative recovery in four compartments (vein, peritoneum, extraperitoneal space
      and hind leg muscle). Subsequently, intravenous and intraperitoneal bolus
      infusion experiments were performed and pharmacokinetic parameters were
      calculated. RESULTS: In vitro, compatibility of mitomycin C and microdialysis
      equipment was demonstrated, and relative recovery was stable over an adequate
      concentration range, moderately increased by raising medium temperature and
      increased when flow rate was reduced, all according to theory. In vivo, stable
      relative recovery was observed over seven hours. Mitomycin C exhibited fast and
      even distribution in rat tissues, and equal bioavailability was achieved by
      intravenous and intraperitoneal infusion. The half-life of mitomycin C calculated
      after intravenous infusion was 40 minutes. CONCLUSIONS: Mitomycin C concentration
      can be reliable monitored in vivo using microdialysis, suggesting that this
      technique can be used in pharmacokinetic studies of this drug during hyperthermic
      intraperitoneal chemotherapy.

PMID- 20809962
TI  - Evolutionary loss of 8-oxo-G repair components among eukaryotes.
AB  - BACKGROUND: We have examined the phylogenetic pattern among eukaryotes of
      homologues of the E. coli 7,8-dihydro-8-oxoguanine (8-oxo-G) repair enzymes MutY,
      MutM, and MutT. RESULTS: These DNA repair enzymes are present in all large
      phylogenetic groups, with MutM homologues being the most universally conserved.
      All chordates and echinoderms were found to possess all three 8-oxo-G repair
      components. Likewise, the red and green algae examined have all three repair
      enzymes, while all land-living plants have MutY and MutM homologues, but lack
      MutT. However, for some phyla, e.g. protostomes, a more patchy distribution was
      found. Nematodes provide a striking example, where Caenorhabditis is the only
      identified example of an organism group having none of the three repair enzymes,
      while the genome of another nematode, Trichinella spiralis, instead encodes all
      three. The most complex distribution exists in fungi, where many different
      patterns of retention or loss of the three repair components are found. In
      addition, we found sequence insertions near or within the catalytic sites of
      MutY, MutM, and MutT to be present in some subgroups of Ascomycetes. CONCLUSION:
      The 8-oxo-G repair enzymes are ancient in origin, and loss of individual 8-oxo-G
      repair components at several distinct points in evolution appears to be the most
      likely explanation for the phylogenetic pattern among eukaryotes.

PMID- 20809963
TI  - Vitamin A status of healthy children in Manisa, Turkey.
AB  - BACKGROUND: Vitamin A deficiency is a major public health nutrition problem in
      the developing world. Even subclinical Vitamin A deficiency is associated with
      increased childhood mortality. Severe maternal vitamin A deficiency may cause
      increased mortality in the first months of life. There have been a limited number
      of studies regarding vitamin A status in Turkey. The aim of this study was to
      assess vitamin A status of healthy children in Manisa, Turkey. METHODS: Vitamin A
      status of 100 healthy children aged 36-48 months is evaluated. The children were
      seen during routine examination. Serum retinol concentrations were measured by
      high-performance liquid chromatography. Duration of breast feeding, age solid
      foods introduced, use of supplementary vitamins, weight and height, and intake of
      specific groups of nutrients on a daily, weekly and monthly basis were collected
      from a questionnaire completed by the mothers. Height and weight z-scores were
      calculated according to national standards. Mothers of 20 of the 100 children
      were known to have normal serum and breast milk retinol concentrations. Children
      with normal serum retinol concentration were compared with the children with VAD.
      Student's t-test and Mann-Whitney test were used to compare independent
      variables. The Pearson correlation analysis test was used to test relation
      between numeric variables. RESULTS: Mean retinol concentration was 0.98 +/- 0.32
      MUmol/L in the whole study group. Serum retinol concentrations were normal (>0.70
      MUmol/L) in 89% of the children. When children with normal serum retinol
      concentrations were compared with those with retinol concentrations lower than
      0.70 MUmol/L, there was no difference in terms of age, gender, weight and height
      at the time of study, z-scores, birth weight, birth length, duration of breast
      feeding, time to begin solid food, rate of supplementary vitamin use, and rate of
      infections (P > 0.05). There was not any relation between vitamin A
      concentrations and weight and height at the time of study, z-scores, birth
      weight, birth length, duration of breast feeding, time to begin solid food,
      vitamin use, and frequency of intake of specific groups of nutrients (P > 0.05).
      CONCLUSIONS: This study showed that VAD is a moderate health problem in Manisa.

PMID- 20809964
TI  - Safety of artemether-lumefantrine in pregnant women with malaria: results of a
      prospective cohort study in Zambia.
AB  - BACKGROUND: Safety data regarding exposure to artemisinin-based combination
      therapy in pregnancy are limited. This prospective cohort study conducted in
      Zambia evaluated the safety of artemether-lumefantrine (AL) in pregnant women
      with malaria. METHODS: Pregnant women attending antenatal clinics were assigned
      to groups based on the drug used to treat their most recent malaria episode (AL
      vs. sulphadoxine-pyrimethamine, SP). Safety was assessed using standard and
      pregnancy-specific parameters. Post-delivery follow-up was six weeks for mothers
      and 12 months for live births. Primary outcome was perinatal mortality
      (stillbirth or neonatal death within seven days after birth). RESULTS: Data from
      1,001 pregnant women (AL n = 495; SP n = 506) and 933 newborns (AL n = 466; SP n
      = 467) showed: perinatal mortality (AL 4.2%; SP 5.0%), comprised of early
      neonatal mortality (each group 2.3%), stillbirths (AL 1.9%; SP 2.7%); preterm
      deliveries (AL 14.1%; SP 17.4% of foetuses); and gestational age-adjusted low
      birth weight (AL 9.0%; SP 7.7%). Infant birth defect incidence was 1.8% AL and
      1.6% SP, excluding umbilical hernia. Abortions prior to antenatal care could not
      be determined: abortion occurred in 4.5% of women treated with AL during their
      first trimester; none were reported in the 133 women exposed to SP and/or quinine
      during their first trimester. Overall development (including neurological
      assessment) was similar in both groups. CONCLUSIONS: These data suggest that
      exposure to AL in pregnancy, including first trimester, is not associated with
      particular safety risks in terms of perinatal mortality, malformations, or
      developmental impairment. However, more data are required on AL use during the
      first trimester.

PMID- 20809965
TI  - Reasons for non-vaccination against HPV and future vaccination intentions among
      19-26 year-old women.
AB  - BACKGROUND: Despite CDC recommendations regarding universal catch-up vaccination
      against human papillomavirus (HPV), only about ten percent of young adult women
      in the United States have been vaccinated. The purpose of this study was to
      better understand reasons for non-vaccination among insured 19-26 year-old women
      and to evaluate future vaccination intentions. METHODS: We used an administrative
      claims database from a large US managed care plan to identify women aged 19-26
      for receipt of a mailed survey. From a sample of 1,375 women with no evidence of
      HPV vaccination from June 1, 2006 through April 30, 2007, 222 completed surveys
      were received, of which 185 were eligible for this analysis. The main outcome
      measures were unvaccinated women's attitudes and vaccine awareness, likelihood of
      future action regarding the vaccine, and reasons for inaction. RESULTS: Among the
      185 non-vaccinees, 25.4% were married, 83.2% were white, and 89.2% had a college
      or higher level education. The vaccine was described as very important by 32.4%
      of subjects, and 30.1% had discussed the vaccine with a doctor and received a
      doctor's recommendation. Half or fewer of respondents were "very" or "extremely"
      likely to discuss the vaccine with their doctor (50.0%), do additional research
      on the vaccine (42.6%), ask a doctor to get the vaccine (37.5%), or make an
      appointment to get the vaccine (27.8%), while 48.0% were "somewhat", "very", or
      "extremely" likely to do nothing to get the vaccine. Among the latter, reasons
      for taking no action included being married or in a monogamous relationship
      (54.9%), belief that the vaccine is too new (35.4%), not having enough
      information about the vaccine (31.7%), concerns about side effects (24.4%), and
      uncertainty about insurance coverage (24.4%). CONCLUSIONS: Educational
      interventions may be needed to enhance HPV vaccination rates among 19-26 year-old
      women, particularly regarding information about vaccine safety, vaccine efficacy,
      insurance coverage, and the value of vaccination to women in monogamous
      relationships.

PMID- 20809966
TI  - Variation in use of surveillance colonoscopy among colorectal cancer survivors in
      the United States.
AB  - BACKGROUND: Clinical practice guidelines recommend colonoscopies at regular
      intervals for colorectal cancer (CRC) survivors. Using data from a large, multi
      regional, population-based cohort, we describe the rate of surveillance
      colonoscopy and its association with geographic, sociodemographic, clinical, and
      health services characteristics. METHODS: We studied CRC survivors enrolled in
      the Cancer Care Outcomes Research and Surveillance (CanCORS) study. Eligible
      survivors were diagnosed between 2003 and 2005, had curative surgery for CRC, and
      were alive without recurrences 14 months after surgery with curative intent. Data
      came from patient interviews and medical record abstraction. We used a
      multivariate logit model to identify predictors of colonoscopy use. RESULTS:
      Despite guidelines recommending surveillance, only 49% of the 1423 eligible
      survivors received a colonoscopy within 14 months after surgery. We observed
      large regional differences (38% to 57%) across regions. Survivors who received
      screening colonoscopy were more likely to: have colon cancer than rectal cancer
      (OR = 1.41, 95% CI: 1.05-1.90); have visited a primary care physician (OR = 1.44,
      95% CI: 1.14-1.82); and received adjuvant chemotherapy (OR = 1.75, 95% CI: 1.27
      2.41). Compared to survivors with no comorbidities, survivors with moderate or
      severe comorbidities were less likely to receive surveillance colonoscopy (OR =
      0.69, 95% CI: 0.49-0.98 and OR = 0.44, 95% CI: 0.29-0.66, respectively).
      CONCLUSIONS: Despite guidelines, more than half of CRC survivors did not receive
      surveillance colonoscopy within 14 months of surgery, with substantial variation
      by site of care. The association of primary care visits and adjuvant chemotherapy
      use suggests that access to care following surgery affects cancer surveillance.

PMID- 20809967
TI  - Reversal of profound vecuronium-induced neuromuscular block under sevoflurane
      anesthesia: sugammadex versus neostigmine.
AB  - BACKGROUND: Acetylcholinesterase inhibitors cannot rapidly reverse profound
      neuromuscular block. Sugammadex, a selective relaxant binding agent, reverses the
      effects of rocuronium and vecuronium by encapsulation. This study assessed the
      efficacy of sugammadex compared with neostigmine in reversal of profound
      vecuronium-induced neuromuscular block under sevoflurane anesthesia. METHODS:
      Patients aged >=18 years, American Society of Anesthesiologists class 1-4,
      scheduled to undergo surgery under general anesthesia were enrolled in this phase
      III, multicenter, randomized, safety-assessor blinded study. Sevoflurane
      anesthetized patients received vecuronium 0.1 mg/kg for intubation, with
      maintenance doses of 0.015 mg/kg as required. Patients were randomized to receive
      sugammadex 4 mg/kg or neostigmine 70 MUg/kg with glycopyrrolate 14 MUg/kg at 1-2
      post-tetanic counts. The primary efficacy variable was time from start of study
      drug administration to recovery of the train-of-four ratio to 0.9. Safety
      assessments included physical examination, laboratory data, vital signs, and
      adverse events. RESULTS: Eighty three patients were included in the intent-to
      treat population (sugammadex, n = 47; neostigmine, n = 36). Geometric mean time
      to recovery of the train-of-four ratio to 0.9 was 15-fold faster with sugammadex
      (4.5 minutes) compared with neostigmine (66.2 minutes; p < 0.0001) (median, 3.3
      minutes with sugammadex versus 49.9 minutes with neostigmine). No serious drug
      related adverse events occurred in either group. CONCLUSIONS: Recovery from
      profound vecuronium-induced block is significantly faster with sugammadex,
      compared with neostigmine. Neostigmine did not rapidly reverse profound
      neuromuscular block (Trial registration number: NCT00473694).

PMID- 20809968
TI  - Phylogeography and population structure of the grape powdery mildew fungus,
      Erysiphe necator, from diverse Vitis species.
AB  - BACKGROUND: The grape powdery mildew fungus, Erysiphe necator, was introduced
      into Europe more than 160 years ago and is now distributed everywhere that grapes
      are grown. To understand the invasion history of this pathogen we investigated
      the evolutionary relationships between introduced populations of Europe,
      Australia and the western United States (US) and populations in the eastern US,
      where E. necator is thought to be native. Additionally, we tested the hypothesis
      that populations of E. necator in the eastern US are structured based on
      geography and Vitis host species. RESULTS: We sequenced three nuclear gene
      regions covering 1803 nucleotides from 146 isolates of E. necator collected from
      the eastern US, Europe, Australia, and the western US. Phylogeographic analyses
      show that the two genetic groups in Europe represent two separate introductions
      and that the genetic groups may be derived from eastern US ancestors. Populations
      from the western US and Europe share haplotypes, suggesting that the western US
      population was introduced from Europe. Populations in Australia are derived from
      European populations. Haplotype richness and nucleotide diversity were
      significantly greater in the eastern US populations than in the introduced
      populations. Populations within the eastern US are geographically differentiated;
      however, no structure was detected with respect to host habitat (i.e., wild or
      cultivated). Populations from muscadine grapes, V. rotundifolia, are genetically
      distinct from populations from other Vitis host species, yet no differentiation
      was detected among populations from other Vitis species. CONCLUSIONS: Multilocus
      sequencing analysis of the grape powdery mildew fungus is consistent with the
      hypothesis that populations in Europe, Australia and the western US are derived
      from two separate introductions and their ancestors were likely from native
      populations in the eastern US. The invasion history of E. necator follows a
      pattern consistent with plant-mediated dispersal, however, more exhaustive
      sampling is required to make more precise conclusions as to origin. E. necator
      shows no genetic structure across Vitis host species, except with respect to V.
      rotundifolia.

PMID- 20809969
TI  - New protective battle-dress impregnated against mosquito vector bites.
AB  - BACKGROUND: Mixing repellent and organophosphate (OP) insecticides to better
      control pyrethroid resistant mosquito vectors is a promising strategy developed
      for bed net impregnation. Here, we investigated the opportunity to adapt this
      strategy to personal protection in the form of impregnated clothes. METHODS: We
      compared standard permethrin impregnated uniforms with uniforms manually
      impregnated with the repellent KBR3023 alone and in combination with an
      organophosphate, Pirimiphos-Methyl (PM). Tests were carried out with Aedes
      aegypti, the dengue fever vector, at dusk in experimental huts. RESULTS: Results
      showed that the personal protection provided by repellent KBR3023-impregnated
      uniforms is equal to permethrin treated uniforms and that KBR3023/PM-impregnated
      uniforms are more protective. CONCLUSION: The use of repellents alone or combined
      with OP on clothes could be promising for personal protection of military troops
      and travellers if residual activity of the repellents is extended and safety is
      verified.

PMID- 20809970
TI  - Promoter methylation and large intragenic rearrangements of DPYD are not
      implicated in severe toxicity to 5-fluorouracil-based chemotherapy in
      gastrointestinal cancer patients.
AB  - BACKGROUND: Severe toxicity to 5-fluorouracil (5-FU) based chemotherapy in
      gastrointestinal cancer has been associated with constitutional genetic
      alterations of the dihydropyrimidine dehydrogenase gene (DPYD). METHODS: In this
      study, we evaluated DPYD promoter methylation through quantitative methylation
      specific PCR and screened DPYD for large intragenic rearrangements in peripheral
      blood from 45 patients with gastrointestinal cancers who developed severe 5-FU
      toxicity. DPYD promoter methylation was also assessed in tumor tissue from 29
      patients RESULTS: Two cases with the IVS14+1G > A exon 14 skipping mutation
      (c.1905+1G > A), and one case carrying the 1845 G > T missense mutation (c.1845G
      > T) in the DPYD gene were identified. However, DPYD promoter methylation and
      large DPYD intragenic rearrangements were absent in all cases analyzed.
      CONCLUSIONS: Our results indicate that DPYD promoter methylation and large
      intragenic rearrangements do not contribute significantly to the development of 5
      FU severe toxicity in gastrointestinal cancer patients, supporting the need for
      additional studies on the mechanisms underlying genetic susceptibility to severe
      5-FU toxicity.

PMID- 20809971
TI  - Genomic amplification of BCR/ABL1 and a region downstream of ABL1 in chronic
      myeloid leukaemia: a FISH mapping study of CML patients and cell lines.
AB  - BACKGROUND: Chronic myeloid leukaemia (CML) is characterized by the expression of
      the BCR/ABL1 fusion gene, a constitutively activated tyrosine kinase that
      commonly results from the formation of the Philadelphia (Ph) chromosome after a
      t(9;22)(q34;q11) or variant rearrangement. The duplication of the Ph chromosome
      is a recurring abnormality acquired during disease progression, whereas
      intrachromosomal amplification of BCR/ABL1 is a rare phenomenon and has been
      associated with imatinib therapy resistance. Archival bone marrow chromosome
      suspensions from 19 CML patients known to carry more than 1 copy of BCR/ABL1 and
      10 CML cell lines were analyzed by fluorescent in situ hybridization with a panel
      of probes from 9q34.1-qter to investigate whether they carried two identical
      copies of the Ph chromosome or, instead, one or both Ph contained cryptic
      imbalances of some regions. RESULTS: A duplication of the entire Ph chromosome
      with no further events involving the derivative 22 was found in 12 patients. In
      contrast, a sideline with either 1 or 2 isochromosomes of the Ph chromosome was
      identified in 6 patients but none of the cell lines. In one of the patients a
      translocation between the distal end of one arm of the isoderivative chromosome
      22 and a third chromosome was revealed. 2 patients were found to carry marker
      structures harbouring high copy number gains of BCR/ABL1 fusion along with a
      variable part of 9q34 region downstream of ABL1 breakpoint, similarly to the
      markers present in the imatinib resistant cell line K562. We identified the
      following regions of amplification: 9q34.1 -> q34.2 and 9q34.1 -> qter, with a
      common minimum amplified region of 682 Kb. One of the patients had 5 BCR/ABL1
      positive clones with variable level of 9q34 amplifications on a variety of
      structures, from an isoderivative 22 to tandem duplications. CONCLUSIONS: These
      data confirm that the intrachromosomal genomic amplification of BCR/ABL1 that
      occurs in some CML patients during disease progression also involves
      amplification of 9q34 gene-rich sequences downstream of ABL1 breakpoint. The
      variety of rearrangements identified in this relatively small cohort demonstrates
      that the Ph chromosome is not a stable structure but prone to further
      rearrangements during disease progression.

PMID- 20809972
TI  - Recurrent myelitis after allogeneic stem cell transplantation. Report of two
      cases.
AB  - BACKGROUND: Allogeneic and autologous haematopoietic stem cell transplantation
      are established treatment options for haematological malignancies and may
      possibly be employed to treat a range of genetic and autoimmune diseases. CASE
      PRESENTATION: We report two patients who developed an acute myelitis within their
      thoracic spinal cord after allogeneic stem cell transplantation. Myelitis in
      these patients was not related to graft versus host disease or immune
      reconstitution and was responsive to intravenous methylprednisolone and
      cyclophosphamide. CONCLUSIONS: Myelitis is a possibly disabling consequence of
      haematopoietic stem cell transplantation.

PMID- 20809973
TI  - I-kappa-kinase-2 (IKK-2) inhibition potentiates vincristine cytotoxicity in non
      Hodgkin's lymphoma.
AB  - BACKGROUND: IKK-2 is an important regulator of the nuclear factor-kappaB (NF
      kappaB) which has been implicated in survival, proliferation and apoptosis
      resistance of lymphoma cells. In this study, we investigated whether inhibition
      of IKK-2 impacts cell growth or cytotoxicity of selected conventional
      chemotherapeutic agents in non-Hodgkin's lymphoma.Two established model systems
      were used; Follicular (WSU-FSCCL) and Diffuse Large Cell (WSU-DLCL2) Lymphoma,
      both of which constitutively express p-IkappaB. A novel, selective small molecule
      inhibitor of IKK-2, ML120B (N-[6-chloro-7-methoxy-9H-beta-carbolin-8-yl]-2
      methylnicotinamide) was used to perturb NF-kappaB in lymphoma cells. The growth
      inhibitory effect of ML120B (M) alone and in combination with cyclophosphamide
      monohydrate (C), doxorubicin (H) or vincristine (V) was evaluated in vitro using
      short-term culture assay. We also determined efficacy of the combination in vivo
      using the SCID mouse xenografts. RESULTS: ML120B down-regulated p-IkappaBalpha
      protein expression in a concentration dependent manner, caused growth inhibition,
      increased G0/G1 cells, but did not induce apoptosis. There was no significant
      enhancement of cell kill in the M/C or M/H combination. However, there was strong
      synergy in the M/V combination where the vincristine concentration can be lowered
      by a hundred fold in the combination for comparable G2/M arrest and apoptosis.
      ML120B prevented vincristine-induced nuclear translocation of p65 subunit of NF
      kappaB. In vivo, ML120B was effective by itself and enhanced CHOP anti-tumor
      activity significantly (P = 0.001) in the WSU-DLCL2-SCID model but did not
      prevent CNS lymphoma in the WSU-FSCCL-SCID model. CONCLUSIONS: For the first
      time, this study demonstrates that perturbation of IKK-2 by ML120B leads to
      synergistic enhancement of vincristine cytotoxicity in lymphoma. These results
      suggest that disruption of the NF-kappaB pathway is a useful adjunct to cytotoxic
      chemotherapy in lymphoma.

PMID- 20809974
TI  - Benefits of biomarker selection and clinico-pathological covariate inclusion in
      breast cancer prognostic models.
AB  - INTRODUCTION: Multi-marker molecular assays have impacted management of early
      stage breast cancer, facilitating adjuvant chemotherapy decisions. We generated
      prognostic models that incorporate protein-based molecular markers and clinico
      pathological variables to improve survival prediction. METHODS: We used a
      quantitative immunofluorescence method to study protein expression of 14 markers
      included in the Oncotype DXTM assay on a 638 breast cancer patient cohort with 15
      year follow-up. We performed cross-validation analyses to assess performance of
      multivariate Cox models consisting of these markers and standard clinico
      pathological covariates, using an average time-dependent Area Under the Receiver
      Operating Characteristic curve and compared it to nested Cox models obtained by
      robust backward selection procedures. RESULTS: A prognostic index derived from a
      multivariate Cox regression model incorporating molecular and clinico
      pathological covariates (nodal status, tumor size, nuclear grade, and age) is
      superior to models based on molecular studies alone or clinico-pathological
      covariates alone. Performance of this composite model can be further improved
      using feature selection techniques to prune variables. When stratifying patients
      by Nottingham Prognostic Index (NPI), most prognostic markers in high and low NPI
      groups differed. Similarly, for the node-negative, hormone receptor-positive sub
      population, we derived a compact model with three clinico-pathological variables
      and two protein markers that was superior to the full model. CONCLUSIONS:
      Prognostic models that include both molecular and clinico-pathological covariates
      can be more accurate than models based on either set of features alone.
      Furthermore, feature selection can decrease the number of molecular variables
      needed to predict outcome, potentially resulting in less expensive assays.

PMID- 20809975
TI  - The in vivo efficacy of two administration routes of a phage cocktail to reduce
      numbers of Campylobacter coli and Campylobacter jejuni in chickens.
AB  - BACKGROUND: Poultry meat is one of the most important sources of human
      campylobacteriosis, an acute bacterial enteritis which is a major problem
      worldwide. Campylobacter coli and Campylobacter jejuni are the most common
      Campylobacter species associated with this disease. These pathogens live in the
      intestinal tract of most avian species and under commercial conditions they
      spread rapidly to infect a high proportion of the flock, which makes their
      treatment and prevention very difficult. Bacteriophages (phages) are naturally
      occurring predators of bacteria with high specificity and also the capacity to
      evolve to overcome bacterial resistance. Therefore phage therapy is a promising
      alternative to antibiotics in animal production. This study tested the efficacy
      of a phage cocktail composed of three phages for the control of poultry infected
      with C. coli and C. jejuni. Moreover, it evaluated the effectiveness of two
      routes of phage administration (by oral gavage and in feed) in order to provide
      additional information regarding their future use in a poultry unit. RESULTS: The
      results indicate that experimental colonisation of chicks was successful and that
      the birds showed no signs of disease even at the highest dose of Campylobacter
      administered. The phage cocktail was able to reduce the titre of both C. coli and
      C. jejuni in faeces by approximately 2 log10 cfu/g when administered by oral
      gavage and in feed. This reduction persisted throughout the experimental period
      and neither pathogen regained their former numbers. The reduction in
      Campylobacter titre was achieved earlier (2 days post-phage administration) when
      the phage cocktail was incorporated in the birds' feed. Campylobacter strains
      resistant to phage infection were recovered from phage-treated chickens at a
      frequency of 13%. These resistant phenotypes did not exhibit a reduced ability to
      colonize the chicken guts and did not revert to sensitive types. CONCLUSIONS: Our
      findings provide further evidence of the efficacy of phage therapy for the
      control of Campylobacter in poultry. The broad host range of the novel phage
      cocktail enabled it to target both C. jejuni and C. coli strains. Moreover the
      reduction of Campylobacter by approximately 2 log10cfu/g, as occurred in our
      study, could lead to a 30-fold reduction in the incidence of campylobacteriosis
      associated with consumption of chicken meals (according to mathematical models).
      To our knowledge this is the first report of phage being administered in feed to
      Campylobacter-infected chicks and our results show that it lead to an earlier and
      more sustainable reduction of Campylobacter than administration by oral gavage.
      Therefore the present study is of extreme importance as it has shown that
      administering phages to poultry via the food could be successful on a commercial
      scale.

PMID- 20809976
TI  - Intensive intervention for children and adolescents with autism in a community
      setting in Italy: a single-group longitudinal study.
AB  - BACKGROUND: Previous studies have shown favourable results with intensive
      behavioural treatment for children with autism: evidence has emerged that
      treatment can be successfully implemented in a community setting and in
      adolescent participants. The aim of this study was to describe the 2-year
      adaptive functioning outcome of children and adolescents with autism treated
      intensively within the context of special autism centres, as well as to evaluate
      family satisfaction with the activity of the centres. METHODS: Sixty participants
      with autism (20 females and 40 males, aged between 4 and 18 years) attending the
      semi-residential rehabilitation centres for autism located in the Abruzzo region
      (Central Italy) were followed up and their adaptive functioning was evaluated
      both at baseline and after one and two years using the Vineland Adaptive
      Behaviour Scales (VABS). Parents' satisfaction with the service was evaluated
      using the Orbetello Satisfaction Scale for Children and Adolescent Mental Health.
      RESULTS: The increase in VABS scores was significant on several domains in the
      different gender and age categories. It is worth noting that male children had
      improved a great deal (roughly, an effect size >0.20) in the domains of
      communication, daily living and motor skills (effect sizes 0.34, 0.45 and 0.27
      respectively) whereas in male adolescents, a notable increase in VABS scores was
      recorded in the domain of socialization only (effect size 0.23). On the other
      hand, adaptive behaviour in female children increased in the domains of
      socialization and motor skills (effect sizes 0.27 and 0.42 respectively) whereas
      in female adolescents, good results were achieved in the domains of daily living,
      socialization and motor skills (effect sizes 0.22, 0.26 and 0.20
      respectively).The level of satisfaction of users of the service over time was
      found to be substantial, even when they had recently started the program.
      CONCLUSIONS: Our results support the implementation of special autism treatment
      community centres, based on a parent co-directed rehabilitative, intensive and
      early intervention. Further experimental research designed to document the
      effectiveness of services provided to children and adolescents with autism in the
      community is recommended.

PMID- 20809977
TI  - Deficits in fine motor skills in a genetic animal model of ADHD.
AB  - BACKGROUND: In an attempt to model some behavioral aspects of Attention
      Deficit/Hyperactivity Disorder (ADHD), we examined whether an existing genetic
      animal model of ADHD is valid for investigating not only locomotor hyperactivity,
      but also more complex motor coordination problems displayed by the majority of
      children with ADHD. METHODS: We subjected young adolescent Spontaneously
      Hypertensive Rats (SHRs), the most commonly used genetic animal model of ADHD, to
      a battery of tests for motor activity, gross motor coordination, and skilled
      reaching. Wistar (WIS) rats were used as controls. RESULTS: Similar to children
      with ADHD, young adolescent SHRs displayed locomotor hyperactivity in a familiar,
      but not in a novel environment. They also had lower performance scores in a
      complex skilled reaching task when compared to WIS rats, especially in the most
      sensitive measure of skilled performance (i.e., single attempt success). In
      contrast, their gross motor performance on a Rota-Rod test was similar to that of
      WIS rats. CONCLUSION: The results support the notion that the SHR strain is a
      useful animal model system to investigate potential molecular mechanisms
      underlying fine motor skill problems in children with ADHD.

PMID- 20809978
TI  - Head and neck cancers in France: an analysis of the hospital medical information
      system (PMSI) database.
AB  - BACKGROUND: With 16,005 new cases and 5,406 related deaths in 2005, France is
      particularly concerned by Head and Neck (H&N) cancers. In addition to tobacco and
      alcohol, Human Papillomavirus (HPV) has been reported as a risk factor for H&N
      cancers. The literature on the burden of these cancers in Europe is scarce. This
      study was performed to assess the medical and economical burden of
      hospitalisations for H&N cancers in France. METHODS: The French national hospital
      database (PMSI), in which admissions to public and private hospitals are
      recorded, was retrospectively analysed to assess the annual number of patients
      hospitalised for H&N cancers and associated hospital costs from the healthcare
      payer perspective. ICD-10 codes (16 codes classified as oral cavity, oropharynx,
      pharynx, salivary glands and larynx) were used to extract admissions for these
      cancers. Hospital stays, chemotherapy and radiotherapy sessions were extracted to
      assess patients' management. Costs of admissions were obtained from French
      official tariffs. RESULTS: In 2007, there were 36 268 patients hospitalised for
      H&N cancers, of whom 81% were men, corresponding to 60 200 hospital stays and 287
      846 sessions of chemo- or radio-therapy. Oropharynx cancer was the most frequent
      (28% of patients), followed by oral cavity cancer (25% of patients). The peak of
      frequency was observed in the 55-59 years age group. Patients were mainly treated
      in medicine (48%) and surgery (23%) units. Mean annual cost per patient ranged
      from ?2,764 to ?7,673 leading to a total hospital cost of ?323 millions in 2007
      (including hospitalization and expensive drugs). With 26% of H&N cancers
      attributable to HPV infections, 9 430 patients were hospitalized due to HPV
      related H&N cancers, representing ?138 million in 2007. CONCLUSION: Even without
      taking into account the rehabilitation costs, the hospital burden of H&N cancers
      is considerable.

PMID- 20809979
TI  - Characterization of the beta amyloid precursor protein-like gene in the central
      nervous system of the crab Chasmagnathus. Expression during memory consolidation.
AB  - BACKGROUND: Human beta-amyloid, the main component in the neuritic plaques found
      in patients with Alzheimer's disease, is generated by cleavage of the beta
      amyloid precursor protein. Beyond the role in pathology, members of this protein
      family are synaptic proteins and have been associated with synaptogenesis,
      neuronal plasticity and memory, both in vertebrates and in invertebrates.
      Consolidation is necessary to convert a short-term labile memory to a long-term
      and stable form. During consolidation, gene expression and de novo protein
      synthesis are regulated in order to produce key proteins for the maintenance of
      plastic changes produced during the acquisition of new information. RESULTS: Here
      we partially cloned and sequenced the beta-amyloid precursor protein like gene
      homologue in the crab Chasmagnathus (cappl), showing a 37% of identity with the
      fruit fly Drosophila melanogaster homologue and 23% with Homo sapiens but with
      much higher degree of sequence similarity in certain regions. We observed a wide
      distribution of cappl mRNA in the nervous system as well as in muscle and gills.
      The protein localized in all tissues analyzed with the exception of muscle.
      Immunofluorescence revealed localization of cAPPL in associative and sensory
      brain areas. We studied gene and protein expression during long-term memory
      consolidation using a well characterized memory model: the context-signal
      associative memory in this crab species. mRNA levels varied at different time
      points during long-term memory consolidation and correlated with cAPPL protein
      levels CONCLUSIONS: cAPPL mRNA and protein is widely distributed in the central
      nervous system of the crab and the time course of expression suggests a role of
      cAPPL during long-term memory formation.

PMID- 20809980
TI  - Penta-O-galloyl-beta-D-glucose induces G1 arrest and DNA replicative S-phase
      arrest independently of cyclin-dependent kinase inhibitor 1A, cyclin-dependent
      kinase inhibitor 1B and P53 in human breast cancer cells and is orally active
      against triple negative xenograft growth.
AB  - INTRODUCTION: Natural herbal compounds with novel actions different from existing
      breast cancer (BCa) treatment modalities are attractive for improving therapeutic
      efficacy and safety. We have recently shown that penta-1,2,3,4,6-O-galloyl-beta-D
      glucose (PGG) induced S-phase arrest in prostate cancer (PCa) cells through
      inhibiting DNA replicative synthesis and G(1) arrest, in addition to inducing
      cell death at higher levels of exposure. We and others have shown that PGG
      through intraperitoneal (i.p.) injection exerts a strong in vivo growth
      suppression of human PCa xenograft models in athymic nude mice. This study aims
      to test the hypothesis that the novel targeting actions of PGG are applicable to
      BCa cells, especially those lacking proven druggable targets. METHODS: Mono-layer
      cell culture models of p53-wild type estrogen receptor (ER)-dependent MCF-7 BCa
      cells and p53-mutant ER-/progesterone receptor (PR)- and Her2-regular (triple
      negative) MDA-MB-231 BCa were exposed to PGG for a comprehensive investigation of
      cellular consequences and molecular targets/mediators. To test the in vivo
      efficacy, female athymic mice inoculated with MDA-MB-231 xenograft were treated
      with 20mg PGG/kg body weight by daily gavage starting 4 days after cancer cell
      inoculation. RESULTS: Exposure to PGG induced S-phase arrest in both cell lines
      as indicated by the lack of 5-bromo2'-deoxy-uridine (BrdU) incorporation into S
      phase cells as well as G(1) arrest. Higher levels of PGG induced more caspase
      mediated apoptosis in MCF-7, in strong association with induction of P53 Ser(15)
      phosphorylation, than in MDA-MB-231 cells. The cell cycle arrests were achieved
      without an induction of cyclin dependent kinase (CDK) inhibitory proteins
      P21(Cip1) and P27(Kip1). PGG treatment led to decreased cyclin D1 in both cell
      lines and over-expressing cyclin D1 attenuated G(1) arrest and hastened S arrest.
      In serum-starvation synchronized MCF-7 cells, down-regulation of cyclin D1 was
      associated with de-phosphorylation of retinoblastoma (Rb) protein by PGG shortly
      before G(1)-S transition. In vivo, oral administration of PGG led to a greater
      than 60% inhibition of MDA-MB231 xenograft growth without adverse effect on host
      body weight. CONCLUSIONS: Our in vitro and in vivo data support PGG as a
      potential drug candidate for breast cancer with novel targeting actions,
      especially for a triple negative BCa xenograft model.

PMID- 20809982
TI  - A specialist-generalist classification of the arable flora and its response to
      changes in agricultural practices.
AB  - BACKGROUND: Theory in ecology points out the potential link between the degree of
      specialisation of organisms and their responses to disturbances and suggests that
      this could be a key element for understanding the assembly of communities. We
      evaluated this question for the arable weed flora as this group has scarcely been
      the focus of ecological studies so far and because weeds are restricted to
      habitats characterised by very high degrees of disturbance. As such, weeds offer
      a case study to ask how specialization relates to abundance and distribution of
      species in relation to the varying disturbance regimes occurring in arable crops.
      RESULTS: We used data derived from an extensive national monitoring network of
      approximately 700 arable fields scattered across France to quantify the degree of
      specialisation of 152 weed species using six different ecological methods. We
      then explored the impact of the level of disturbance occurring in arable fields
      by comparing the degree of specialisation of weed communities in contrasting
      field situations.The classification of species as specialist or generalist was
      consistent between different ecological indices. When applied on a large-scale
      data set across France, this classification highlighted that monoculture harbour
      significantly more specialists than crop rotations, suggesting that crop rotation
      increases abundance of generalist species rather than sets of species that are
      each specialised to the individual crop types grown in the rotation. Applied to a
      diachronic dataset, the classification also shows that the proportion of
      specialist weed species has significantly decreased in cultivated fields over the
      last 30 years which suggests a biotic homogenization of agricultural landscapes.
      CONCLUSIONS: This study shows that the concept of generalist/specialist species
      is particularly relevant to understand the effect of anthropogenic disturbances
      on the evolution of plant community composition and that ecological theories
      developed in stable environments are valid in highly disturbed environments such
      as agro-ecosystems. The approach developed here to classify arable weeds
      according to the breadth of their ecological niche is robust and applicable to a
      wide range of organisms. It is also sensitive to disturbance regime and we show
      here that recent changes in agricultural practices, i.e. increased levels of
      disturbance have favoured the most generalist species, hence leading to biotic
      homogenisation in arable landscapes.

PMID- 20809981
TI  - Microenvironment alters epigenetic and gene expression profiles in Swarm rat
      chondrosarcoma tumors.
AB  - BACKGROUND: Chondrosarcomas are malignant cartilage tumors that do not respond to
      traditional chemotherapy or radiation. The 5-year survival rate of histologic
      grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has
      been established--namely, the Swarm Rat Chondrosarcoma (SRC)--and shown to
      resemble the human disease. Previous studies with this model revealed that tumor
      microenvironment could significantly influence chondrosarcoma malignancy.
      METHODS: To examine the effect of the microenvironment, SRC tumors were initiated
      at different transplantation sites. Pyrosequencing assays were utilized to assess
      the DNA methylation of the tumors, and SAGE libraries were constructed and
      sequenced to determine the gene expression profiles of the tumors. Based on the
      gene expression analysis, subsequent functional assays were designed to determine
      the relevancy of the specific genes in the development and progression of the
      SRC. RESULTS: The site of transplantation had a significant impact on the
      epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that
      SRC tumors were hypomethylated compared to control tissue, and that tumors at
      each transplantation site had a unique expression profile. Subsequent functional
      analysis of differentially expressed genes, albeit preliminary, provided some
      insight into the role that thymosin-beta4, c-fos, and CTGF may play in
      chondrosarcoma development and progression. CONCLUSION: This report describes the
      first global molecular characterization of the SRC model, and it demonstrates
      that the tumor microenvironment can induce epigenetic alterations and changes in
      gene expression in the SRC tumors. We documented changes in gene expression that
      accompany changes in tumor phenotype, and these gene expression changes provide
      insight into the pathways that may play a role in the development and progression
      of chondrosarcoma. Furthermore, specific functional analysis indicates that
      thymosin-beta4 may have a role in chondrosarcoma metastasis.

PMID- 20809983
TI  - Forward-time simulation of realistic samples for genome-wide association studies.
AB  - BACKGROUND: Forward-time simulations have unique advantages in power and
      flexibility for the simulation of genetic samples of complex human diseases
      because they can closely mimic the evolution of human populations carrying these
      diseases. However, a number of methodological and computational constraints have
      prevented the power of this simulation method from being fully explored in
      existing forward-time simulation methods. RESULTS: Using a general-purpose
      forward-time population genetics simulation environment, we developed a forward
      time simulation method that can be used to simulate realistic samples for genome
      wide association studies. We examined the properties of this simulation method by
      comparing simulated samples with real data and demonstrated its wide
      applicability using four examples, including a simulation of case-control samples
      with a disease caused by multiple interacting genetic and environmental factors,
      a simulation of trio families affected by a disease-predisposing allele that had
      been subjected to either slow or rapid selective sweep, and a simulation of a
      structured population resulting from recent population admixture. CONCLUSIONS:
      Our algorithm simulates populations that closely resemble the complex structure
      of the human genome, while allows the introduction of signals of natural
      selection. Because of its flexibility to generate different types of samples with
      arbitrary disease or quantitative trait models, this simulation method can
      simulate realistic samples to evaluate the performance of a wide variety of
      statistical gene mapping methods for genome-wide association studies.

PMID- 20809984
TI  - Morphologic transformation of human breast epithelial cells MCF-10A: dependence
      on an oxidative microenvironment and estrogen/epidermal growth factor receptors.
AB  - BACKGROUND: MCF-10A, immortalized but non-transformed human breast epithelial
      cells, are widely used in research examining carcinogenesis. The studies
      presented here were initiated with the observation that MCF-10A cells left in
      continuous culture for prolonged periods without re-feeding were prone to the
      development of transformed foci. We hypothesized that the depletion of labile
      culture components led to the onset of processes culminating in the observed cell
      transformation. The purpose of this study was to define the factors which
      promoted transformation of this cell line. RESULTS: Changes in levels of phenol
      red (PHR), hydrocortisone (HC), and epidermal growth factor (EGF) with or without
      estrogen treatment indicated that both oxidative stress- and estrogen receptor
      alpha (ERalpha)-mediated pathways contribute to cell transformation. Gene array
      and Western blotting analyses of cells maintained in our laboratory and of those
      from other sources documented detectable ERalpha and ERbeta (ERbeta) in this
      ERalpha-negative cataloged cell line. Results also indicate the possibility of a
      direct association of EGF receptor (EGFR) and ERalpha in these cells as well as
      the formation and high induction of a novel ternary complex that includes ERbeta
      (ERalpha/ERbeta/EGFR) in cells grown under conditions facilitating
      transformation. CONCLUSIONS: Our studies resulted in the development of a growth
      protocol where the effects of chronic, physiologically relevant alterations in
      the microenvironment on cellular transformation were examined. From our results,
      we were able to propose a model of transformation within the MCF-10A cell line in
      which oxidative stress, ER and EGFR play essential roles. Overall, our work
      indicates that the immediate microenvironment of cells exerts powerful growth
      cues which ultimately determine their transformation potential.

PMID- 20809985
TI  - Prevalence and risk factors of hepatitis B and C viruses among haemodialysis
      patients in Gaza strip, Palestine.
AB  - BACKGROUND: The prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV)
      and its associated risk factors among haemodialysis (HD) patients in Gaza strip
      was investigated using serological and molecular techniques. RESULTS: The overall
      prevalence of HBV among the four HD centers was 8.1%. The main risk factors were
      HD center (p=0.05), history of blood transfusion (p<0.01), and treatment abroad
      (p=0.01). The overall prevalence of HCV among the four HD centers was 22%. The
      main risk factors were HD center (p<0.01), time duration on HD (p<0.01), history
      of blood transfusion (p<0.01), treatment abroad (p<0.01), and history of blood
      transfusion abroad (p<0.01). Serum aminotransferases levels decreased in HD
      patients compared with normal population but still there was a direct association
      between the activity of liver enzymes and both HBV (p<0.01) and HCV (p<0.01)
      infection. CONCLUSION: The much higher prevalence of Hepatitis viruses among HD
      patients compared to the normal population of Gaza strip indicates a causative
      relation between HD and hepatitis viruses transmission. Therefore extremely
      careful observation of preventive infection control measures is essential to
      limit Hepatitis viruses' transmission in HD centers.

PMID- 20809986
TI  - MRS-guided HDR brachytherapy boost to the dominant intraprostatic lesion in high
      risk localised prostate cancer.
AB  - BACKGROUND: It is known that the vast majority of prostate cancers are
      multifocal. However radical radiotherapy historically treats the whole gland
      rather than individual cancer foci.Magnetic resonance spectroscopy (MRS) can be
      used to non-invasively locate individual cancerous tumours in prostate. Thus an
      intentionally non-uniform dose distribution treating the dominant intraprostatic
      lesion to different dose levels than the remaining prostate can be delivered
      ensuring the maximum achievable tumour control probability.The aim of this study
      is to evaluate, using radiobiological means, the feasibility of a MRS-guided high
      dose rate (HDR) brachytherapy boost to the dominant lesion. METHODS: Computed
      tomography and MR/MRS were performed for treatment planning of a high risk
      localised prostate cancer. Both were done without endorectal coil, which distorts
      shape of prostate during the exams.Three treatment plans were compared:- external
      beam radiation therapy (EBRT) only- combination of EBRT and HDR brachytherapy-
      combination of EBRT and HDR brachytherapy with a synchronous integrated boost to
      the dominant lesionThe criteria of plan comparison were: the minimum, maximum and
      average doses to the targets and organs at risk; dose volume histograms;
      biologically effective doses for organs at risk and tumour control probability
      for the target volumes consisting of the dominant lesion as detected by MR/MRS
      and the remaining prostate volume. RESULTS: Inclusion of MRS information on the
      location of dominant lesion allows a safe increase of the dose to the dominant
      lesion while dose to the remaining target can be even substantially decreased
      keeping the same, high tumour control probability. At the same time an improved
      urethra sparing was achieved comparing to the treatment plan using a combination
      of EBRT and uniform HDR brachytherapy. CONCLUSIONS: MRS-guided HDR brachytherapy
      boost to dominant lesion has the potential to spare the normal tissue, especially
      urethra, while keeping the tumour control probability high.

PMID- 20809987
TI  - Matrix metalloproteinase-25 has a functional role in mouse secondary palate
      development and is a downstream target of TGF-beta3.
AB  - BACKGROUND: Development of the secondary palate (SP) is a complex event and
      abnormalities during SP development can lead to cleft palate, one of the most
      common birth disorders. Matrix metalloproteinases (MMPs) are required for proper
      SP development, although a functional role for any one MMP in SP development
      remains unknown. MMP-25 may have a functional role in SP formation as genetic
      scans of the DNA of human cleft palate patients indicate a common mutation at a
      region upstream of the MMP-25 gene. We report on the gene expression profile of
      MMP-25 in the developing mouse SP and identify its functional role in mouse SP
      development. RESULTS: MMP-25 mRNA and protein are found at all SP developmental
      stages in mice, with the highest expression at embryonic day (E) 13.5.
      Immunohistochemistry and in situ hybridization localize MMP-25 protein and mRNA,
      respectively, to the apical palate shelf epithelial cells and apical mesenchyme.
      MMP-25 knockdown with siRNA in palatal cultures results in a significant decrease
      in palate shelf fusion and persistence of the medial edge epithelium. MMP-25 mRNA
      and protein levels significantly decrease when cultured palate shelves are
      incubated in growth medium with 5 MUg/mL of a TGF-beta3-neutralizing antibody.
      CONCLUSIONS: Our findings indicate: (i) MMP-25 gene expression is highest at
      E12.5 and E13.5, which corresponds with increasing palate shelf growth downward
      alongside the tongue; (ii) MMP-25 protein and mRNA expression predominantly
      localize in the apical epithelium of the palate shelves, but are also found in
      apical areas of the mesenchyme; (iii) knockdown of MMP-25 mRNA expression impairs
      palate shelf fusion and results in significant medial edge epithelium remaining
      in contacted areas; and (iv) bio-neutralization of TGF-beta3 significantly
      decreases MMP-25 gene expression. These data suggest a functional role for MMP-25
      in mouse SP development and are the first to identify a role for a single MMP in
      mouse SP development.

PMID- 20809988
TI  - Efficient Bayesian approach for multilocus association mapping including gene
      gene interactions.
AB  - BACKGROUND: since the introduction of large-scale genotyping methods that can be
      utilized in genome-wide association (GWA) studies for deciphering complex
      diseases, statistical genetics has been posed with a tremendous challenge of how
      to most appropriately analyze such data. A plethora of advanced model-based
      methods for genetic mapping of traits has been available for more than 10 years
      in animal and plant breeding. However, most such methods are computationally
      intractable in the context of genome-wide studies. Therefore, it is hardly
      surprising that GWA analyses have in practice been dominated by simple
      statistical tests concerned with a single marker locus at a time, while the more
      advanced approaches have appeared only relatively recently in the biomedical and
      statistical literature. RESULTS: we introduce a novel Bayesian modeling framework
      for association mapping which enables the detection of multiple loci and their
      interactions that influence a dichotomous phenotype of interest. The method is
      shown to perform well in a simulation study when compared to widely used standard
      alternatives and its computational complexity is typically considerably smaller
      than that of a maximum likelihood based approach. We also discuss in detail the
      sensitivity of the Bayesian inferences with respect to the choice of prior
      distributions in the GWA context. CONCLUSIONS: our results show that the Bayesian
      model averaging approach which explicitly considers gene-gene interactions may
      improve the detection of disease associated genetic markers in two respects:
      first, by providing better estimates of the locations of the causal loci; second,
      by reducing the number of false positives. The benefits are most apparent when
      the interacting genes exhibit no main effects. However, our findings also
      illustrate that such an approach is somewhat sensitive to the prior distribution
      assigned on the model structure.

PMID- 20809990
TI  - The sarcoplasmic Ca2+-ATPase: design of a perfect chemi-osmotic pump.
AB  - The sarcoplasmic (SERCA 1a) Ca2+-ATPase is a membrane protein abundantly present
      in skeletal muscles where it functions as an indispensable component of the
      excitation-contraction coupling, being at the expense of ATP hydrolysis involved
      in Ca2+/H+ exchange with a high thermodynamic efficiency across the sarcoplasmic
      reticulum membrane. The transporter serves as a prototype of a whole family of
      cation transporters, the P-type ATPases, which in addition to Ca2+ transporting
      proteins count Na+, K+-ATPase and H+, K+-, proton- and heavy metal transporting
      ATPases as prominent members. The ability in recent years to produce and analyze
      at atomic (2.3-3 A) resolution 3D-crystals of Ca2+-transport intermediates of
      SERCA 1a has meant a breakthrough in our understanding of the structural aspects
      of the transport mechanism. We describe here the detailed construction of the
      ATPase in terms of one membraneous and three cytosolic domains held together by a
      central core that mediates coupling between Ca2+-transport and ATP hydrolysis.
      During turnover, the pump is present in two different conformational states, E1
      and E2, with a preference for the binding of Ca2+ and H+, respectively. We
      discuss how phosphorylated and non-phosphorylated forms of these conformational
      states with cytosolic, occluded or luminally exposed cation-binding sites are
      able to convert the chemical energy derived from ATP hydrolysis into an
      electrochemical gradient of Ca2+ across the sarcoplasmic reticulum membrane. In
      conjunction with these basic reactions which serve as a structural framework for
      the transport function of other P-type ATPases as well, we also review the role
      of the lipid phase and the regulatory and thermodynamic aspects of the transport
      mechanism.

PMID- 20809989
TI  - Increased levels of CRP and MCP-1 are associated with previously unknown abnormal
      glucose regulation in patients with acute STEMI: a cohort study.
AB  - BACKGROUND: Inflammation plays an important role in the pathophysiology of both
      atherosclerosis and type 2 diabetes and some inflammatory markers may also
      predict the risk of developing type 2 diabetes. The aims of the present study
      were to assess a potential association between circulating levels of inflammatory
      markers and hyperglycaemia measured during an acute ST-elevation myocardial
      infarction (STEMI) in patients without known diabetes, and to determine whether
      circulating levels of inflammatory markers measured early after an acute STEMI,
      were associated with the presence of abnormal glucose regulation classified by an
      oral glucose tolerance test (OGTT) at three-month follow-up in the same cohort.
      METHODS: Inflammatory markers were measured in fasting blood samples from 201
      stable patients at a median time of 16.5 hours after a primary percutaneous
      coronary intervention (PCI). Three months later the patients performed a
      standardised OGTT. The term abnormal glucose regulation was defined as the sum of
      the three pathological glucose categories classified according to the WHO
      criteria (patients with abnormal glucose regulation, n = 50). RESULTS: No
      association was found between inflammatory markers and hyperglycaemia measured
      during the acute STEMI. However, the levels of C-reactive protein (CRP) and
      monocyte chemoattractant protein-1 (MCP-1) measured in-hospital were higher in
      patients classified three months later as having abnormal compared to normal
      glucose regulation (p = 0.031 and p = 0.016, respectively). High levels of CRP
      (>= 75 percentiles (33.13 mg/L)) and MCP-1 (>= 25 percentiles (190 ug/mL)) were
      associated with abnormal glucose regulation with an adjusted OR of 3.2 (95% CI
      1.5, 6.8) and 7.6 (95% CI 1.7, 34.2), respectively. CONCLUSION: Elevated levels
      of CRP and MCP-1 measured in patients early after an acute STEMI were associated
      with abnormal glucose regulation classified by an OGTT at three-month follow-up.
      No significant associations were observed between inflammatory markers and
      hyperglycaemia measured during the acute STEMI.

PMID- 20809991
TI  - Competitive Memory Training (COMET) for low self-esteem in patients with
      personality disorders: a randomized effectiveness study.
AB  - BACKGROUND: Self-esteem is a major concern in the treatment of patients with
      personality disorders in general. In patients with borderline personality
      disorder, low self-esteem is associated with factors contributing to suicidal and
      self-injurious behaviour. At the moment there are no well-proven interventions
      that specifically target low self-esteem. Recently, a new approach, Competitive
      Memory Training or COMET, aimed at the enhancement of retrieving beneficial
      information from memory, appeared to be successful in addressing low self-esteem
      in different patient populations. AIMS: To assess whether COMET for low self
      esteem is also an effective intervention for patients with personality disorders.
      METHOD: 91 patients with personality disorders who were already in therapy in a
      regular mental health institution were randomly assigned to either 7 group
      sessions of COMET in addition to their regular therapy or to 7 weeks of ongoing
      regular therapy. These latter patients received COMET after their "7 weeks
      waiting period for COMET". All patients that completed COMET were contacted 3
      months later to assess whether the effects of COMET had remained stable. RESULTS:
      Compared to the patients who received regular therapy only, patients in the COMET
      + regular therapy condition improved significantly and with large effect sizes on
      indices of self-esteem and depression. Significant differential improvements on
      measures of autonomy and social optimism were also in favour of COMET, but had
      small to intermediate effect sizes. The therapeutic effects of COMET remained
      stable after 3 months on three out of the four outcome measures. CONCLUSION:
      COMET for low self-esteem seems to be an efficacious trans-diagnostic approach
      that can rather easily be implemented in the treatment of patients with
      personality disorders.

PMID- 20809992
TI  - Dying of corruption.
AB  - In many poor countries, over 80% of the population have experienced corrupt
      practices in the health sector. In rich countries, corruption takes other forms
      such as overbilling. The causal link between low levels of the quality of
      government (QoG) and population health can be either direct or indirect. Using
      cross-sectional data from more than 120 countries, our findings are that more of
      a QoG variable is positively associated with higher levels of life expectancy,
      lower levels of mortality rates for children and mothers, higher levels of
      healthy life expectancies and higher levels of subjective health feelings. In
      contrast to the strong relationships between the QoG variables and the health
      indicators, the relationship between the health-spending measures and population
      health are rather weak most of the time and occasionally non-existent. Moreover,
      for private health spending as well as for private share of total health
      spending, the relation to good health is close to zero or slightly negative. The
      policy recommendation coming out of our study to improve health levels around the
      world, in rich countries as well as in poor countries, is to improve the QoG and
      to finance health care with public, not private, money.

PMID- 20809993
TI  - Domestic violence and obesity in Egyptian women.
AB  - Domestic violence and obesity are global public health problems.This study
      explores associations of domestic violence and obesity in 5015 ever-married, non
      pregnant women aged 15-49 years who took part in the 2005 Egypt Demographic and
      Health Survey (EDHS). Women's mean body mass index (BMI) was 30.4 kg/m2, and 48%
      were obese. Thirty-seven percent reported any prior psychological, physical or
      sexual domestic violence.Compared with their counterparts, the adjusted odds of
      being obese were marginally higher among women who reported any prior sexual
      (aOR=1.31),physical or sexual (aOR=1.18), or psychological, physical or sexual
      (aOR=1.17) domestic violence. Women who experienced severe or repeated domestic
      violence--as measured by reported exposure to three or more acts of
      physical(aOR=1.25), psychological or physical (aOR=1.18), physical or
      sexual(aOR=1.36), and psychological, physical or sexual (aOR=1.26) domestic
      violence--had higher adjusted odds of being obese. Marginally significant
      adjusted dose-response relationships remained between obesity and the number of
      specific acts of: (1) physical or sexual violence and (2) psychological, physical
      or sexual domestic violence. Obesity among women in poorer settings like Egypt
      may partly have its roots in gender subordination, as manifested in women's
      exposure to multiple acts of domestic violence.

PMID- 20809994
TI  - The relationship between elderly suicide rates and telephone use: a cross
      national study.

PMID- 20809995
TI  - Bupropion in the treatment of depression in Parkinson's disease.
AB  - A 78-year-old female with a nine-year history of depression was hospitalized due
      to worsening depression and symptoms associated with Parkinson's disease (PD).
      Her motor abilities improved on levodopa and the depression improved after a
      trial of bupropion, following unsuccessful treatment with other antidepressants.
      We found four reports on successful treatment of depression in PD with bupropion.
      However, no controlled double-blind studies have been conducted so clinicians
      should be cautious when administering bupropion in depression in PD.

PMID- 20809996
TI  - Activity of the enzyme adenosine deaminase in serum, erythrocytes and lymphocytes
      of rats infected with Trypanosoma evansi.
AB  - In Trypanosoma evansi infections changes in the haemogram are commonly observed,
      and the enzyme adenosine deaminase (ADA) plays an important role in the
      production and differentiation of blood cells. Thus, the aim of this study was to
      evaluate the activity of ADA in serum, erythrocytes and lymphocytes of rats
      infected with T. evansi compared to non-infected rats. Thirty adult rats were
      used, divided into 3 uniform groups. The animals in groups A and B were infected
      intraperitoneally with 2 x 106 trypomastigotes/rat. Rodents from group C (control
      group), were not-infected. Blood collection was performed on days 4 and 20 post
      infection (p.i.) in order to obtain acute and chronic infection stages of
      disease. The blood was used to assess the activity of ADA. In the blood, reduced
      haematocrit and increased lymphocytes were correlated with ADA activity in
      erythrocytes and lymphocytes. We observed reduction of ADA activity in serum and
      erythrocytes in rats infected with T. evansi compared to non-infected rats (P <
      0.05). ADA activity in lymphocytes was decreased after 4 days, when the
      parasitaemia was high and increased after 20 days, when the number of circulating
      parasites was low. In conclusion, our results showed that the ADA activity was
      altered in serum, lymphocytes and erythrocytes of rats, concomitantly with
      haematological parameters, in experimental infection by T. evansi.

PMID- 20809997
TI  - Kraepelin's concept of psychiatric illness.
AB  - Emil Kraepelin fundamentally shaped our current psychiatric nosology. Although
      much has been written about his diagnostic formulations, less is known about his
      views on the fundamental nature of psychiatric illness and the goals of
      psychiatric nosology. We focus on his writings from 1896 to 1903 but also review
      his inaugural lecture in Dorpat in 1887 and his last two papers, published in
      1919-1920. Kraepelin hoped for a ' natural ' classification of psychiatric
      illness but realized that the level of etiologic knowledge required to undergird
      this effort was not feasible in his own lifetime. This did not stop him, however,
      from developing a pragmatic approach based on his clinical method of careful
      description with detailed follow-up, coupled with the available fallible tools of
      pathological anatomy and, by 1919, genetics and biochemistry. Kraepelin saw
      psychiatric disorders as multifactorial, arising from the difficult to untangle
      action and interaction of internal and external causes. He was aware of the
      problem of defining the boundaries of illness and health but knew this was not
      unique to psychiatry. Contrary to his stereotype, he was sensitive to the
      importance of personality factors in psychiatric illness and advocated for their
      investigation. He also recognized the limitations of his ' clinical method' and
      was especially critical of classifications based on single prominent symptoms.
      Ultimately, Kraepelin was a skeptical realist when it came to psychiatric
      nosology. His goal of developing a consistent ' natural ' classification of the
      major mental disorders has yet to be attained, but his ' research agenda' remains
      central to psychiatry to the present day.

PMID- 20809998
TI  - A calcium-activated nucleotidase secreted from Ostertagia ostertagi 4th-stage
      larvae is a member of the novel salivary apyrases present in blood-feeding
      arthropods.
AB  - Apyrases (ATP-diphosphohydrolase) comprise a ubiquitous class of glycosylated
      nucleotidases that hydrolyse extracellular ATP and ADP to orthophosphate and AMP.
      One class of newly-described, Ca2+-dependent, salivary apyrases known to
      counteract blood-clotting, has been identified in haematophagous arthropods.
      Herein, we have identified a gene (Oos-apy-1) encoding a protein that
      structurally conforms to the Ca2+-activated apyrase from the bed bug, Cimex
      lectularius, by immunologically screening an Ostertagia L4 cDNA expression
      library. The expressed protein (rOos-APY-1) was biochemically functional in the
      presence of Ca2+ only, with greatest activity on ATP, ADP, UTP and UDP. Host
      antibodies to the fusion protein appeared as early as 14 days post-infection
      (p.i.) and increased through 30 days p.i. Immunohistochemical and Western blot
      analyses demonstrated that the native Oos-APY-1 protein is present in the
      glandular bulb of the oesophagus and is confined to the L4. A putative signal
      sequence at the N-terminus and near 100% identity with a Teladorsagia
      circumcincta L4 secreted protein is consistent with the native protein being
      secreted at the cellular level. Predicated upon substrate specificity, the native
      protein may be used by the parasite to control the levels of host extracellular
      nucleotides released by locally-damaged tissues in an effort to modulate immune
      intervention and inflammation.

PMID- 20809999
TI  - Positive symptoms and white matter microstructure in never-medicated first
      episode schizophrenia.
AB  - BACKGROUND: We investigated cerebral structural connectivity and its relationship
      to symptoms in never-medicated individuals with first-onset schizophrenia using
      diffusion tensor imaging (DTI). METHOD: We recruited subjects with first episode
      DSM-IV schizophrenia who had never been exposed to antipsychotic medication
      (n=34) and age-matched healthy volunteers (n=32). All subjects received DTI and
      structural magnetic resonance imaging scans. Patients' symptoms were assessed on
      the Positive and Negative Syndrome Scale. Voxel-based analysis was performed to
      investigate brain regions where fractional anisotropy (FA) values significantly
      correlated with symptom scores. RESULTS: In patients with first-episode
      schizophrenia, positive symptoms correlated positively with FA scores in white
      matter associated with the right frontal lobe, left anterior cingulate gyrus,
      left superior temporal gyrus, right middle temporal gyrus, right middle cingulate
      gyrus, and left cuneus. Importantly, FA in each of these regions was lower in
      patients than controls, but patients with more positive symptoms had FA values
      closer to controls. We found no significant correlations between FA and negative
      symptoms. CONCLUSIONS: The newly-diagnosed, neuroleptic-naive patients had lower
      FA scores in the brain compared with controls. There was positive correlation
      between FA scores and positive symptoms scores in frontotemporal tracts,
      including left fronto-occipital fasciculus and left inferior longitudinal
      fasciculus. This implies that white matter dysintegrity is already present in the
      pre-treatment phase and that FA is likely to decrease after clinical treatment or
      symptom remission.

PMID- 20810000
TI  - Letter to the Editor: are antipsychotics good or bad for the brain? A comment on
      Moncrieff & Leo (2010).

PMID- 20810001
TI  - Relationship between cognitive functioning and 6-month clinical and functional
      outcome in patients with first manic episode bipolar I disorder.
AB  - BACKGROUND: Although cognitive deficits in bipolar disorder have been associated
      with diminished functional outcome, this relationship has been studied primarily
      through cross-sectional designs, and has not been studied in patients early in
      the course of illness. The purpose of this study was to evaluate the impact of
      cognitive functioning on longitudinal 6-month functional and clinical outcome in
      recently diagnosed clinically stable patients with bipolar disorder. METHOD: A
      total of 53 recently diagnosed patients with DSM-IV bipolar disorder type I were
      assessed within 3 months of their first manic episode using a neuropsychological
      battery measuring verbal/pre-morbid intellectual functioning, learning/memory,
      spatial/non-verbal reasoning, attention/processing speed and executive function.
      Functional outcome was assessed at baseline and 6 months using the
      Multidimensional Scale of Independent Functioning (MSIF) and DSM-IV Global
      Assessment of Functioning Scale (GAF). Clinical outcome was assessed with symptom
      ratings and by monitoring onset of new mood episodes. RESULTS: Memory,
      particularly verbal learning/memory, was robustly associated with 6-month
      functional outcome on the MSIF, even after partialling out the influence of mood
      symptoms and substance abuse co-morbidity. Depression ratings at 6 months, but
      not cognitive variables, were associated with 6-month GAF scores. Cognitive
      functioning was not associated with 6-month clinical outcome. CONCLUSIONS: Memory
      was associated with 6-month longitudinal functional but not clinical outcome in
      recently diagnosed patients with bipolar disorder. These data further support the
      distinction between clinical and functional outcome, and emphasize the need for
      identification of, and development of treatments for, cognitive impairments early
      in the course of bipolar disorder.

PMID- 20810002
TI  - Relationship of monoamine oxidase A binding to adaptive and maladaptive
      personality traits.
AB  - BACKGROUND: Monoamine oxidase A (MAOA) is an important enzyme that metabolizes
      monoamines such as serotonin, norepinephrine and dopamine in the brain. In
      prefrontal cortex, low MAOA binding is associated with aggression and high
      binding is associated with major depressive disorder (MDD) and also risk for
      recurrence of depressive episodes. In rodent models, low MAOA levels are
      associated with increased aggression and fear conditioning, and decreased social
      and exploratory investigative behaviors. Our objective was to measure MAOA
      binding in prefrontal cortex and concurrently evaluate a broad range of validated
      personality traits. We hypothesized that prefrontal MAOA binding would correlate
      negatively with angry-hostility, a trait related to aggression/anger, and
      positively with traits intuitively related to adaptive investigative behavior.
      METHOD: Participants were aged 19-49 years, healthy and non-smoking. MAOA binding
      was measured with [11C]harmine positron emission tomography (PET) in prefrontal
      brain regions and personality traits were measured with the NEO Personality
      Inventory Revised (NEO PI-R). RESULTS: Prefrontal MAOA binding correlated
      negatively with angry-hostility (r=-0.515, p=0.001) and positively with
      deliberation (r=0.514, p=0.001). In a two-factor regression model, these facets
      explained 38% of variance in prefrontal MAOA binding. A similar relationship was
      found in prefrontal cortex subregions. CONCLUSIONS: We propose a new continuum
      describing the relationship between personality and MAOA: deliberate/thoughtful
      contrasting aggressive/impulsive. Additionally, the association between high MAOA
      binding and greater deliberation may explain why some people have moderately high
      levels of MAOA, although very high levels occur during MDD. In health, higher
      MAOA binding is associated with an adaptive personality facet.

PMID- 20810003
TI  - The use of well controls: an unhealthy practice in psychiatric research.
AB  - BACKGROUND: Studies comparing cases with controls to uncover the causes of
      psychiatric disorders are common in biological research. The validity of these
      studies depends upon adherence to the methodological principles underlying the
      case-control design. However, these principles are often violated. One common
      practice that violates these principles is the use of well controls. In this
      paper we describe the bias that it can cause and discuss why the use of well
      controls leads to invalidity in case-control studies. METHOD: Using hypothetical
      numerical examples we illustrate the consequences of using well controls.
      RESULTS: The results illustrate that the use of well controls can cause
      substantial bias. In no instance does the use of well controls improve validity.
      CONCLUSIONS: We conclude that the use of well controls is an unhealthy practice
      in psychiatric research.

PMID- 20810004
TI  - Face emotion recognition is related to individual differences in psychosis
      proneness.
AB  - BACKGROUND: Deficits in face emotion recognition (FER) in schizophrenia are well
      documented, and have been proposed as a potential intermediate phenotype for
      schizophrenia liability. However, research on the relationship between psychosis
      vulnerability and FER has mixed findings and methodological limitations.
      Moreover, no study has yet characterized the relationship between FER ability and
      level of psychosis-proneness. If FER ability varies continuously with psychosis
      proneness, this suggests a relationship between FER and polygenic risk factors.
      METHOD: We tested two large internet samples to see whether psychometric
      psychosis-proneness, as measured by the Schizotypal Personality Questionnaire
      Brief (SPQ-B), is related to differences in face emotion identification and
      discrimination or other face processing abilities. RESULTS: Experiment 1 (n=2332)
      showed that psychosis-proneness predicts face emotion identification ability but
      not face gender identification ability. Experiment 2 (n=1514) demonstrated that
      psychosis-proneness also predicts performance on face emotion but not face
      identity discrimination. The tasks in Experiment 2 used identical stimuli and
      task parameters, differing only in emotion/identity judgment. Notably, the
      relationships demonstrated in Experiments 1 and 2 persisted even when individuals
      with the highest psychosis-proneness levels (the putative high-risk group) were
      excluded from analysis. CONCLUSIONS: Our data suggest that FER ability is related
      to individual differences in psychosis-like characteristics in the normal
      population, and that these differences cannot be accounted for by differences in
      face processing and/or visual perception. Our results suggest that FER may
      provide a useful candidate intermediate phenotype.

PMID- 20810005
TI  - Five-year outcome of cognitive behavioral therapy and exposure with response
      prevention for bulimia nervosa.
AB  - BACKGROUND: Few data exist examining the longer-term outcome of bulimia nervosa
      (BN) following treatment with cognitive behavioral therapy (CBT) and exposure
      with response prevention (ERP). METHOD: One hundred and thirty-five women with
      purging BN received eight sessions of individual CBT and were then randomly
      assigned to either relaxation training (RELAX) or one of two ERP treatments, pre
      binge (B-ERP) or pre-purge cues (P-ERP). Participants were assessed yearly
      following treatment and follow-up data were recorded. RESULTS: Eighty-one per
      cent of the total sample attended long-term follow-up. At 5 years, abstinence
      rates from binging were significantly higher for the two exposure treatments (43%
      and 54%) than for relaxation (27%), with no difference between the two forms of
      exposure. Over 5 years, the frequency of purging was lower for the exposure
      treatments than for relaxation training. Rates of recovery varied according to
      definition of recovery. Recovery continued to increase to 5 years. At 5 years,
      83% no longer met DSM-III-R criteria for BN, 65% received no eating disorder
      diagnosis, but only 36% had been abstinent from bulimic behaviors for the past
      year. CONCLUSIONS: This study provides possible evidence of a conditioned
      inoculation from exposure treatment compared with relaxation training in long
      term abstinence from binge eating at 5 years, and the frequency of purging over 5
      years, but not for other features of BN. Differences among the groups were not
      found prior to 5 years. CBT is effective for BN, yet a substantial group remains
      unwell in the long term. Definition of recovery impacts markedly on recovery
      rates.

PMID- 20810006
TI  - Is there reduced susceptibility to praziquantel in Schistosoma  japonicum?
      Evidence from China.
AB  - Praziquantel is widely used for the treatment of human schistosomiasis. However,
      in recent years, there has been increasing concern about the resistance of
      Schistosoma species to praziquantel. The study described here was designed to
      evaluate the current susceptibility to praziquantel in S. japonicum in China.
      During the non-transmission period of schistosomiasis, a random sample of 4760
      subjects from the main endemic foci of China were examined using parasitological
      stool examination. In total, 584 subjects were identified as being infected with
      S. japonicum, with a prevalence rate of 12.27%. Among them, 565 stool-egg
      positive subjects were treated with praziquantel in a single oral dose of 40
      mg/kg. Six weeks post-treatment, among the 505 villagers re-examined, 480
      (95.05%) had no detectable S. japonicum eggs. Twenty-one subjects still excreting
      eggs after the first treatment were treated with praziquantel for the second
      time. All stool samples, including those from those participants with second
      treatment were re-examined 6 weeks after the second treatment, and no stool-egg
      positives were found. The results indicate that the current efficacy of
      praziquantel against S. japonicum is still high and has not changed after more
      than 2 decades of repeated, expanded chemotherapy in the main endemic areas of
      China. It is suggested that no evidence of tolerance or resistance to
      praziquantel in S. japonicum was detected in China.

PMID- 20810007
TI  - Cloning and sequence analysis of Bufo arenarum oviductin cDNA and detection of
      its orthologous gene expression in the mouse female reproductive tract.
AB  - The glycoprotein envelope surrounding the Bufo arenarum egg exists in different
      functional forms. Conversion between types involves proteolysis of specific
      envelope glycoproteins. When the egg is released from the ovary, the envelope
      cannot be penetrated by sperm. Conversion to a penetrable state occurs during
      passage through the pars recta portion of the oviduct, where oviductin, a serine
      protease with trypsin-like substrate specificity, hydrolyzes two kinds of
      envelope glycoproteins: gp84 and gp55. The nucleotide sequence of a 3203 bp B.
      arenarum oviductin cDNA was obtained. Deduced amino acid sequence showed a
      complete open reading frame encoding 980 amino acids. B. arenarum oviductin is a
      multi-domain protein with a protease domain at the N-terminal region followed by
      two CUB domains and toward the C-terminal region another protease domain, which
      lacked an active histidine site, and one CUB domain. Expression of ovochymase 2,
      the mammalian orthologous of amphibian oviductin, was assayed in mouse female
      reproductive tract. Ovochymase 2 mRNA was unnoticeable in the mouse oviduct but
      expression was remarkable in the uterus. Phylogenetic relationship between
      oviductin and ovochymase 2 opens the possibility to understand the role of this
      enzyme in mammalian reproduction.

PMID- 20810008
TI  - Role of cyclic AMP in the maturation of Ciona intestinalis oocytes.
AB  - Immature oocytes are arrested at prophase I of the meiotic process and maturation
      onset is indicated by oocyte nuclear disassembly (germinal vesicle breakdown or
      GVBD). Signaling pathways that elevate intracellular cyclic AMP (cAMP) may either
      prevent or induce oocyte maturation depending on the species. In some marine
      invertebrates and, in particular, in ascidian oocytes, cAMP triggers GVBD rather
      than blocking it. In this paper, we tested different cAMP elevators in fully
      grown oocytes at the germinal vesicle stage (GV) of the ascidian Ciona
      intestinalis. We demonstrated that through the activation of adenylate cyclase or
      the inhibition and phosphodiesterases the oocyte remained at the GV stage. This
      effect was reversible as the GV-arrested oocytes, rinsed and incubated in sea
      water, are able to undergo spontaneous maturation and extrusion of follicle
      cells. In addition, oocytes acquire the ability to be fertilized and start early
      development. However, morphology of follicle cells, embryos and larvae from in
      vitro matured oocytes showed different morphology from those derived from in vivo
      mature oocytes. The role and the transduction mechanism of cAMP in the regulation
      of oocyte maturation were discussed. Finally, we indicated a variation of
      biological mechanisms present in the ascidian species; moreover, we sustain
      evidence proving that tunicates share some biological mechanisms with
      vertebrates. This information provided new hints on the importance of ascidians
      in the evolution of chordates.

PMID- 20810009
TI  - Functional outcomes after neonatal open cardiac surgery: comparison of survivors
      of the Norwood staged procedure and the arterial switch operation.
AB  - BACKGROUND: Improvements in long-term survival of children undergoing the Norwood
      staged procedure and the arterial switch operation have resulted in the need to
      prepare these at-risk children for each stage of their developmental trajectory,
      including school readiness. This study describes and compares functional outcomes
      following the Norwood staged procedure and arterial switch operations. METHODS:
      This prospective inception cohort study comprised a sample of 73 children (71%
      boys) who had the Norwood staged procedure (n = 28) or the arterial switch
      operation (n = 45) at the age of 6 weeks or younger at the Stollery Children's
      Hospital, Edmonton, Alberta, between 2002 and 2005. We excluded children who had
      chromosomal abnormalities or cerebral palsy. When children were 18-24 months of
      age, parents completed the Adaptive Behavioral Assessment System II. Standard
      scores for the domains are mean 100, standard deviation (15); skill area scaled
      scores, 10 (3). Student's t-test with Bonferonni correction was used to compare
      groups. RESULTS: This population has greater than four times the number of
      children delayed on the General Adaptive Composite than the normative group.
      Functional outcomes were similar in the two groups other than those of home
      living (Norwood: 8.8 (2.8) compared with arterial switch: 11.2 (3.1), t = 3.389,
      p = 0.001) and self-care (Norwood: 5.9 (3.5) versus arterial switch: 8.1 (2.6), t
      = 3.140, p = 0.002). CONCLUSION: These survivors are at increased risk for
      delayed functional abilities. Self-care, necessary for independence and
      confidence as children reach school age, was particularly low in the Norwood
      group. Reasons for low self-care abilities require further study.

PMID- 20810010
TI  - Open anastomosis of extracardiac conduit for total cavopulmonary connection
      decreases post-operative pleural effusion.
AB  - OBJECTIVE: The goal of this study was to see whether the open anastomosis
      technique using vacuum-assisted venous drainage at the time of the Fontan
      procedure was associated with decreased post-operative pleural effusion. METHODS:
      We analysed a subgroup of patients with a functional single ventricle who
      underwent non-fenestrated total cavopulmonary connection completion with the
      insertion of an extracardiac conduit as the sole or predominant procedure
      conducted by a single surgeon at a single institute, using either an open or
      closed anastomosis technique. RESULTS: Median age and weight were 2.3 years, with
      a range from 1.3 to 27.6 years and 11.4 kilograms, with a range from 9.7 to 43
      kilograms, respectively. The open anastomosis technique was associated with a
      shorter bypass run (p = 0.015), decreased surgical duration (p = 0.032), fewer
      pleural effusion days (p = 0.049), and lesser pleural effusion (p = 0.013) than
      closed anastomosis. Correlation analysis demonstrated a significant relationship
      between the amount of pleural effusion and surgical duration (correlation
      efficient, 0.535; p = 0.033). A logistic regression model showed that the open
      technique was associated with a 20-fold increase in the likelihood of having a
      total chest tube discharge of less than 300 millilitres (p = 0.027). CONCLUSIONS:
      The open anastomosis technique shortens operative duration and bypass run, which
      in turn might contribute to decreased pleural effusion soon after the modified
      Fontan procedure.

PMID- 20810011
TI  - Spatial Architecture of Nitrifying Bacteria Biofilm Immobilized on Polyurethane
      Foam in an Automatic Biodetector for Water Toxicity.
AB  - We describe the architecture of nitrifying bacteria biofilms immobilized on a
      three-dimensional (3D) polyurethane foam that permits efficient water flow
      through a bioreactor. The 3D spatial organization of immobilized bacterial
      colonies is characterized on three resolution levels with X-ray tomography, light
      confocal microscopy, and scanning electron microscopy (SEM). Using these
      techniques we demonstrate biofilm distribution in the foam and the existence of
      several modes of binding of bacteria to the foam. Computed X-ray tomography
      permits observation of the distribution of the biofilm in the whole open cellular
      polyurethane material volume and estimation of biofilm volume. SEM and confocal
      laser scanning microscopy techniques permit 3D visualization of biofilm
      structure. Three distinct immobilization patterns could be observed in the open
      cellular polyurethane material: (1) large irregular aggregates of bacterial
      biofilm that exist as irregular biofilm fragments, rope-like structures, or
      biofilm layers on the foam surface; (2) spherical (pom-pom) aggregates of
      bacteria localized on the external surface of biofilm; and (3) biofilm threads
      adherent to the surface of polyurethane foam. Finally, we demonstrate that
      immobilized bacteria exhibit metabolic activity and growth.

PMID- 20810012
TI  - Current status of soil-transmitted helminthiases among pre-school and school-aged
      children from Ile-Ife, Osun State, Nigeria.
AB  - A cross-sectional survey was conducted to determine the prevalence and intensity
      of soil-transmitted helminths among pre-school and school-aged children attending
      nursery and primary schools in Ile-Ife. Single stool samples were collected
      between January and March, 2009 from 352 children randomly selected from a total
      of 456 children attending both private and government schools. The stool samples
      were processed using the modified Kato-Katz technique, and then examined for the
      eggs of soil-transmitted helminths (STHs). One hundred and twenty-one (34.4%)
      samples were positive for STH eggs. The overall prevalences of Ascaris
      lumbricoides, Trichuris trichiura and hookworm were 33.2%, 3.7% and 0.9%,
      respectively. The prevalence of STH infection in government schools (47.8%) was
      significantly higher than in private schools (16.1%) (P < 0.001). The most common
      type of mixed infection was the combination of A. lumbricoides and T. trichiura
      (6.8%). The prevalence and intensity of A. lumbricoides rose with age. The lowest
      prevalence and intensity (7.7%; 0.240 +/- 0.136 eggs per gram (epg)) were
      recorded in the 2- to 3-year-old age group, while the highest prevalence and
      intensity (58.7%; 1.820 +/- 0.237 epg) were recorded in children aged 10 years
      and above. A questionnaire survey indicated that 73% of the children attending
      private school had been treated with anthelminthics less than 2 months prior to
      the collection of stool specimens, while 43% of the children attending government
      school received anthelminthic treatment during the same period. The findings
      indicate that STH infections are endemic among schoolchildren in Ile-Ife and that
      the burden of parasitic infections is greater in government schools than in
      private schools.

PMID- 20810013
TI  - Reversed rotation of the midgut in adults--a case report.
AB  - Intestinal obstruction is a common surgical emergency. It is often due to
      adhesions; however, when the patient is young and has a virgin abdomen, we have
      to consider uncommon causes. We present a rare case of reversed rotation of the
      midgut as a cause for intestinal obstruction.

PMID- 20810014
TI  - Small bowel trans-vaginal evisceration following vault biopsy: general surgeons
      beware!
AB  - A case-report of vaginal evisceration following vault biopsy is described. This
      case highlights the importance of good surgical technique when performing a
      vaginal biopsy in order to avoid this rare, but life-threatening, complication.
      General surgeons may well be faced with this acute presentation and prompt
      management is vital in order to preserve the involved small bowel.

PMID- 20810015
TI  - To close or not to close? Treatment of abdominal compartment syndrome by
      neuromuscular blockade without laparostomy.
AB  - Abdominal compartment syndrome (ACS) is a recognised postoperative complication
      seen frequently in the intensive care unit (ICU). Surgical decompression and
      laparostomy remain the gold standard treatment for established ACS, combined with
      supportive non-surgical therapy, such as nasogastric decompression. In the
      following case report, we describe our successful management of a patient with
      established postoperative ACS by re-laparotomy to exclude a reversible cause,
      immediate re-closure of the abdomen and prolonged neuromuscular blockade,
      avoiding a laparostomy.

PMID- 20810016
TI  - Varices of the round ligament mimicking an inguinal hernia--an important
      differential diagnosis during pregnancy.
AB  - Pregnancy is a recognised risk factor for the development of inguinal hernias due
      to an increase in intra-abdominal pressure. Whilst often managed conservatively
      until after the pregnancy, if the hernia presents acutely as a painful or tender
      groin lump, urgent or emergency repair may be required. Many clinicians rely
      heavily on clinical examination alone in order to diagnose the presence of such a
      hernia. In pregnancy, however, in order to prevent unnecessary surgery, the use
      of ultrasound has a more important role to play in reaching this diagnosis. We
      report a cautionary case that highlights the need for ultrasound evaluation of
      all painful groin lumps in pregnant women prior to considering surgery.

PMID- 20810017
TI  - Acute presentation of intestinal malrotation in adults: a report of two cases.
AB  - INTRODUCTION: Intestinal malrotation is a rare developmental abnormality
      occurring as a result of incomplete rotation during fetal life. It usually
      presents in the first few weeks of life, but may persist unrecognised into adult
      life. We report two interesting cases in elderly patients both characterised by a
      significant diagnostic challenge due to atypical clinical and radiological signs
      and in one case an unusual complication following laparotomy. CASE REPORTS: The
      first case was a 64-year-old man initially treated for diverticulitis but at
      laparotomy was found to have malrotation of the midgut and a perforated left
      sided appendicitis. The second case was a 76-year-old woman admitted with
      multiple fractures and increasing abdominal distension following a fall. Ten days
      after admission, she underwent right hemicolectomy to treat faecal peritonitis
      due to multiple caecal perforations complicating volvulus in the presence of
      midgut malrotation. CONCLUSIONS: These cases illustrate challenges associated
      with managing patients with undiagnosed intestinal malrotation. Delayed diagnosis
      is a common feature in several case reports describing atypical presentation of
      appendicitis in patients with malrotation. While abdominal CT scan can remove
      much of the diagnostic uncertainty, the diagnosis of malrotation can be missed
      unless there is a high index of suspicion.

PMID- 20810018
TI  - A peculiar case of bilateral, spontaneous thromboses of the pampiniform plexi.
AB  - Acute thrombosis of the pampiniform plexus is an uncommon clinical problem which
      causes a diagnostic conundrum in men presenting urgently to medical personnel. We
      present an unusual case of a young man who presented with metachronous thromboses
      of his pampiniform plexi and review the literature to explore potential
      aetiologies and therapeutic strategies.

PMID- 20810019
TI  - Laparoscopic management of foreign body perforation in diverticular disease.
AB  - A case is described where laparoscopic principles in the management of
      spontaneous sigmoid diverticular perforation are applied to foreign body
      perforation.

PMID- 20810020
TI  - An unusual and life-threatening cause of epigastric pain presenting to the
      general surgical team: a case report.
AB  - As general surgeons, we are regularly referred patients with epigastric pain.
      There are a huge number of common pathologies which cause this complaint, most of
      which are gastrointestinal in origin. Although the old adage goes 'common things
      are common', we must always keep our minds open to the possibility of the
      uncommon and not miss warning signs which are present in the history or
      examination. We present the case of a 59-year-old woman with a ruptured sinus of
      Valsalva aneurysm presenting to the accident and emergency department as
      epigastric pain.

PMID- 20810021
TI  - Safety and application of laparoscopic gastrectomy for benign gastric disease and
      gastric cancer.
AB  - INTRODUCTION: Laparoscopic gastrectomy is rapidly expanding despite reservations
      by some surgeons regarding its safety and radicality. The aim of this study was
      to evaluate patients undergoing laparoscopic gastrectomy for both benign and
      malignant disease with particular emphasis on technical feasibility, safety,
      effectiveness and complications. PATIENTS AND METHODS: Review of prospectively
      collected data of patients who underwent laparoscopic gastrectomy from May 2005
      to September 2009 under the care of one consultant surgeon. RESULTS: A total of
      61 laparoscopic gastrectomies were performed (35 men and 26 women) with a median
      age of 68 years (range, 41-90 years). There were 39 distal gastrectomies (19
      adenocarcinoma, 6 gastrointestinal stromal tumour [GIST], 4 benign gastric outlet
      obstruction, 4 high-grade dysplasia in gastric adenomas, 4 non-healing ulcers, 2
      gastric antral vascular ectasia [GAVE]); 15 sub-total gastrectomies (13
      adenocarcinomas, 2 GIST); and 7 total gastrectomies (5 adenocarcinomas, 1 GIST, 1
      carcinoid). Median follow-up was for 48 months (range, 1-72 months). There was
      one death, two major and six minor complications. All patients with complications
      made a satisfactory recovery. CONCLUSIONS: Laparoscopic gastrectomy is associated
      with a low mortality (1.75%) and major morbidity (3.50%). Although technically
      demanding, especially when a D2 lymphadenectomy is performed, our results have
      shown that tailored laparoscopic resection based on tumour characteristics with
      either D1 or D2 lymphadenectomy results in good surgical and oncological
      outcomes.

PMID- 20810022
TI  - Effect of enzyme modification by well-defined multi-armed poly(ethylene glycol)
      synthesized using polyamidoamine dendron.
AB  - Egg white lysozyme was chemically modified by PEGylated PAMAM 1st, 2nd and 3rd
      generation dendrons, which had 2, 4 and 8 PEG arms, respectively. The number of
      PEG chains introduced to the lysozyme molecule drastically increased with an
      increase in dendron generation, although the number of PEGylated PAMAM dendrons
      introduced decreased due to steric repulsion. The lytic activity of lysozyme to
      Micrococcus luteus cells was effectively inhibited by conjugating PEGylated PAMAM
      dendron to the lysozyme, indicating steric stabilization of PEG chains at the
      surface of lysozyme molecule. In addition, the enzymatic reaction of the lysozyme
      with oligosaccharide substrate was apparently accelerated by a substrate
      condensation effect due to the multi-armed structure of PEG.

PMID- 20810023
TI  - Increased intracranial pressure is associated with elevated cerebrospinal fluid
      ADH levels in closed-head injury.
AB  - OBJECTIVES: Head injury frequently results in increased intracranial pressure and
      brain edema. Investigators have demonstrated that ischemic injury causes an
      increase in cerebrospinal fluid (CSF) levels of antidiuretic hormone (ADH);
      increased CSF ADH levels exacerbate cerebral edema, and inhibition of the ADH
      system with specific ADH antagonists reduces cerebral edema. The current study
      was designed to test the hypothesis that elevated levels of ADH are present in
      the CSF of subjects with head injury. METHODS: Ventricular CSF and blood samples
      were taken from 11 subjects with head injury and 12 subjects with no known head
      trauma or injury. ADH levels were analyzed using radioimmunoassay. Severity of
      increased intracranial pressure (ICP) was rated in head-injured subjects using a
      four-point ordinal scale, based on which treatments were necessary to reduce ICP.
      RESULTS: Subjects with head injury had higher CSF (3.2 versus 1.2 pg/ml; P<0.02)
      and plasma (4.1 versus 1.4 pg/ml; P<0.02) levels of ADH than did control
      subjects. In head-injured subjects, CSF ADH levels positively correlated with
      severity of ICP. DISCUSSION: The results of this study suggest that ADH plays a
      role in brain edema associated with closed head injury.

PMID- 20810024
TI  - Motor unit number estimation in transected peripheral nerves.
AB  - OBJECTIVES: To study motor unit number estimation (MUNE) in acutely transected
      peripheral nerves, and to retest our previous observation which had revealed a
      discordance between the loss of compound muscle action potential (CMAP) size and
      decrease in MUNE during Wallerian degeneration. METHODS: In eight patients with
      nine transected median or ulnar nerves, a total of 18 electrophysiological
      studies were performed before the complete nerve degeneration ensues. CMAP
      recordings and incremental MUNE studies were performed by stimulation of the
      nerves at the wrist level and recording from the appropriate hand muscles. The
      same studies repeated on the contralateral side. RESULTS: Injury side to intact
      side ratios of the MUNEs were significantly higher than the CMAP ratios. Mean
      step areas in MUNE studies were found to be lower on the transected sides after
      72 hours post-injury. DISCUSSION: These findings support the existence of an
      electrophysiologically observable asynchrony in neuromuscular synapse dysfunction
      during Wallerian degeneration.

PMID- 20810025
TI  - Atherosclerotic plaque pathohistology and classification with high-resolution
      MRI.
AB  - OBJECTIVE: A series of research works had proven that high-resolution magnetic
      resonance imaging (MRI) was an effective tool to identify the morphological
      appearance of atherosclerotic vulnerable plaque. We performed further study to
      compare ex vivo vascular morphology with MRI and histological examination using
      the specimens of carotid endarterectomy and femoral artery (FA) prosthetic
      reconstruction, and described the detailed histology and immunohistochemistry
      features of plaque. METHODS: Eight consecutive patients (five males, mean age
      67.4 years) who were recruited into our study had high-grade stenosis or
      occlusion of carotid artery and FA (70 to 100%). Four patients accepted carotid
      endarterectomy and others underwent FA prosthetic reconstruction. RESULTS: The
      high level of accuracy was shown in classification of the plaque type. The
      sections of plaques detected by MRI were classified as follows: 12 (22.2%) were
      modified American Heart Association (AHA) type III, 11 (20.4%) were type IV-V, 26
      (48.2%) were type VI and 5 (9.3%) were type VII. According to the histological
      observations, the overall accurate rate by MRI showed a high level accuracy of
      90.7% (49/54). Immunohistochemistry of cellular components in plaque shoulder
      demonstrated that CD68-positive macrophages were strongly dominated along the
      arterial wall. Reduced expression of smooth muscle actin (SMA)-positive smooth
      muscle cells were detected in the fibrous cap of atheroma. CD31 stain showed the
      increased presence of CD31-positive neomicrovessels. CONCLUSIONS: Atherosclerosis
      is a systematic disease that can involve whole body vascular beds. Non-invasive
      high-resolution MRI will provide useful information in morphological studies of
      the arterial walls and classification of the plaque type.

PMID- 20810026
TI  - Granulocyte colony-stimulating factor enhances cellular proliferation and motor
      function recovery on rats subjected to traumatic brain injury.
AB  - OBJECTIVE: Traumatic brain injury (TBI) results in neurological dysfunction and
      death through primary or secondary mechanisms. Here, we evaluated the effect of
      osmotic pump delivery of granulocyte colony-stimulating factor (G-CSF) on the
      histopathology and motor function recovery of rats after experimental TBI.
      METHODS: Sprague-Dawley rats were used as experimental model by fluid percussion
      device to cause brain injury on the motor cortex area. The rats were
      simultaneously subjected to TBI and were implanted of min-osmotic pump containing
      recombinant human G-CSF (300 MUg/700 MUl) via intraperitoneal injection. Motor
      function was assessed by rotarod test. 5-bromo-2'-deoxyuridine (BrdU) was used to
      label the proliferating cells and their differentiation was evaluated by
      histology and immunohistochemistry. RESULTS: The G-CSF group showed significantly
      better motor function recovery than the control group, and the effect lasted up
      to 14 days after TBI. Moreover, the G-CSF group exhibited a greater increase in
      the number of BrdU-positive cells compared with the control group. The G-CSF
      group also had a significantly higher number of DCX-positive cells in the
      ipsilateral subventricular zone (SVZ) than the control group. CONCLUSIONS: These
      data suggest that the beneficial effect of delivering G-CSF via an osmotic pump
      may improve the motor function and enhance neurogenesis in the SVZ of the injured
      brain.

PMID- 20810027
TI  - Metabolic activity of the subthalamic nucleus in a primate model of L-dopa
      unresponsive parkinsonism.
AB  - Increased activity of the subthalamic nucleus (STN) is critical in mediating
      motor symptoms of Parkinson's disease. To determine if altered STN activity also
      occurs in levodopa (L-Dopa)-unresponsive parkinsonism due to a combined nigral
      and striatal degeneration, metabolic activity of the STN was assessed using
      cytochrome oxidase (CO) histochemistry in monkeys with nigral, striatal, or
      nigral+striatal degeneration induced by 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) and/or 3-nitropropionic acid (3NP). MPTP- and MPTP+3NP
      treated monkeys had a similar parkinsonian score and were clinically
      indistinguishable. However, CO activity in the STN was significantly increased in
      MPTP-induced parkinsonism but not in MPTP+3NP-induced striatonigral degeneration.
      These results indicate that metabolic activity of the STN is normal following a
      combined nigral+striatal degeneration and may help to understand the lack of
      effect of STN stimulation in L-Dopa-unresponsive parkinsonism.

PMID- 20810028
TI  - Functional neural stem cell isolation from brains of adult mutant SOD1
      (SOD1(G93A)) transgenic amyotrophic lateral sclerosis (ALS) mice.
AB  - OBJECTIVES: The aim of present study is to investigate more functional neural
      stem cells (NSCs) could be isolated from brains with amyotrophic lateral
      sclerosis (ALS) and expanded in vitro, based on previous reports demonstrating de
      novo neurogenesis is enhanced to replace degenerating neural tissue. METHODS:
      Thirteen- or eighteen-week-old mutant human Cu/Zn superoxide dismutase
      (SOD1(G93A)) transgenic ALS and wild-type SOD1 transgenic control mice were
      utilized. Changes in numbers of NSCs in the dentate gyrus were analyzed by
      immunohistochemistry against nestin and CD133. NSCs were primarily cultured from
      hippocampus of ALS or control mice. Expression of NSC markers, in vitro expansion
      capacity, and differentiating potential were compared. RESULTS: Hippocampus of 13
      week-old pre-symptomatic ALS mice harbor more cells that can be propagated for
      more than 12 passages in vitro, compared with same age control mice. Primarily
      cultured cells formed neurospheres in the NSC culture medium, expressed NSC
      markers, and differentiated into cells with differentiated neural cell
      characteristics in the differentiation condition confirming that they are NSCs.
      In contrast, long-term expansible NSCs could not be derived from brains of 18
      week-old symptomatic ALS mice with the same experimental techniques, although
      they had comparable nestin-immunoreactive cells in the dentate gyrus. DISCUSSION:
      These results would suggest that increased neuroregeneration in early phase of
      ALS could be translated to regenerative approaches; however, long-term exposure
      to ALS microenvironments could abolish functional capacities of NSCs.

PMID- 20810029
TI  - Self-closing aneurysm clip: a historical review.
AB  - OBJECTIVE: To analyse the self-closing aneurysm clip historical evolution.
      MATERIALS AND METHODS: The authors reviewed the self-closing aneurysm clip's 50
      year history. Major neurosurgical books, journals, testimonials, authors'
      personal experience, and scientific databases were analysed. RESULTS: Self
      closing aneurysm clip malfunction was found to be related to different clip
      strengths (too strong or too weak) and clip's corrosion or fracture due to
      diverse stainless steel biocompatibility issues. It was found that 301, 401, 402,
      58, and 17-7 PH alloys were not suitable for human implantation due to high risk
      of corrosion. In counterpart, 316MOSS, Elgiloy, Phynox, and titanium alloys were
      more biocompatible and less prone to corrosion. The last group showed no motion
      on the magnetic field. Titanium clip has shown to be artifact free on
      computerized tomography followed by high-grade cobalt-chromium clip all the other
      aneurysms clip present a significant artifact. The Federal Drugs and
      Administration/American Society of Testing and Materials (FDA/ASTM) was a major
      contributor on safety development of self-closing aneurysm clip. CONCLUSION: Our
      36-year self-closing aneurysm clip experience is reported.

PMID- 20810030
TI  - Immunomodulatory effectiveness of azithromycin in prevention of postlaminectomy
      epidural fibrosis.
AB  - OBJECTIVE: One of the important causes of failed back surgery is the extensive
      peridural fibrosis collecting in the surgical field after spinal surgeries. Today
      we know that inflammatory mechanisms mediated by the immune system of the body
      plays an important role in generation of fibrosis. Azithromycin, a macrolide
      antibiotic, has proven immunomodulatory effects in various diseases. This study
      aims to investigate the effects of azithromycin on peridural fibrosis. METHODS:
      Twenty-four Wistar rats received laminectomies before dividing them into three
      groups randomly. Animals of the control group received normal saline
      intraperitoneally while animals in the treatment groups received low (20 mg/kg)
      and high (80 mg/kg) doses of azithromycin intraperitoneally after surgical
      interventions. The amount of fibrosis, fibroblast density and inflammatory cell
      density were analyzed histologically. RESULTS: Analysis demonstrated
      significantly reduced fibrosis, fibroblast density and inflammatory cell density
      in treatment groups compared to the control group. There was no difference
      between the treatment groups. CONCLUSION: Immune system plays critical roles in
      tissue repair and fibrogenesis. Results of our study demonstrated that
      azithromycin application reduced formation of peridural fibrosis in experimental
      laminectomy model in rats. Further studies with different dose regimes and
      different application routes are required to carry these results to an advanced
      level.

PMID- 20810031
TI  - Genotype-phenotype correlations in a large series of patients with muscle type
      CPT II deficiency.
AB  - OBJECTIVES: The adult or 'muscular' form of carnitine-palmitoyl-transferase II
      (CPT II) deficiency presents with recurrent rhabdomyolytic episodes and
      myoglobinuria, usually triggered by prolonged exercise. The aim of this study was
      to investigate a large series of patients in order to provide genotype-phenotype
      correlations. METHODS: Our muscle tissue bank was surveyed for patients showing
      attacks of rhabdomyolysis with myoglobinuria. After exclusion of cases affected
      with toxic myoglobinuria, McArdle's disease and Becker muscular dystrophy, over
      100 patients were selected for isotope-exchange radioenzymatic assay of CPT
      enzyme activity in muscle, and 25 cases resulted to be defective. Acylcarnitine
      profile was performed in five patients using tandem mass spectrometry. Mutations
      in the CPT2 gene were identified using DNA sequencing. RESULTS: Although the
      clinical features were rather homogeneous, some patients presented life
      threatening events (acute renal failure) and muscle weakness, and low levels of
      residual CPT activity. The typical acylcarnitine profile found in mutant patients
      confirmed its value as a screening method for further diagnostic investigations.
      We found a high frequency of the common p.Ser113Leu mutation, the recurrence of
      the rare p.Arg631Cys mutation in a genetic isolate in Southern Italy, and
      identified four novel mutations. In some affected patients only one mutant allele
      was found, suggesting either incomplete mutation detection or the possibility
      they are symptomatic carriers. DISCUSSION: Null mutations and homozygous
      mutations were frequently associated with a more severe phenotype and biochemical
      defect. The identification of symptomatic obligate heterozygous carriers might
      suggest that additional epigenetic or environmental factors may contribute to
      determine the phenotype.

PMID- 20810032
TI  - Ultrasound imaging for the rheumatologist. XXVIII. Impact of sonographic knee
      joint involvement in recent-onset inflammatory polyarthritis.
AB  - OBJECTIVES: To assess the impact of the knee joint inflammation, detected by
      ultrasonography (US), on functional disability in patients with recent-onset
      inflammatory polyarthritis (IP). METHODS: We included patients who had IP for
      less than 12 months and who had more than 5 swollen joints. All patients were
      assessed clinically at baseline. US was used to identify joint inflammation at
      multiple joint sites including: hands, wrists, elbows, shoulders, knees, ankles
      and feet. Joint group involvement was defined when at least one joint showed
      intra-articular signs of inflammation (synovial fluid abnormalities and/or
      synovial hypertrophy), according to the OMERACT definitions. Functional
      disability was measured using the health assessment questionnaire (HAQ) score.
      All patients with complete clinical and US data were included in the analysis.
      RESULTS: Patients with US knee involvement showed more active and severe disease
      at baseline. The mean difference of HAQ between patients with and without US knee
      inflammation was 0.42 (95%CI 0.22, 0.62; p<0.001). This difference was still
      clinically and statistically significant even after controllino for disease
      extension and pattern of joint involvement. US shoulder involvement was also
      significantly and independently associated with higher mean HAQ scores.
      CONCLUSIONS: US knee involvement is associated with higher disability in IP at
      first presentation. US is a good tool to help in the differentiation of patients
      with recent-onset IP with different disease severity.

PMID- 20810034
TI  - Resource utilisation and cost of ankylosing spondylitis in Brazil.
AB  - OBJECTIVES: The present study describes resource utilisation in patients with
      ankylosing spondylitis (AS) treated at a tertiary public health facility over a
      one-year period. It also investigates the direct and indirect costs for society
      associated with the treatment of AS. METHODS: Ninety AS patients were selected
      consecutively, and data was analysed retrospectively for one year. Resource
      utilisation was evaluated through systematic interviews with all patients.
      Demographic, socioeconomic, and clinical variables were recorded, and
      questionnaires evaluating quality of life, function, and disease activity were
      also applied (ASQoL, SF-36, HAQ-S, BASFI, and BASDAI). Estimates of indirect
      costs were performed using the human-capital approach based on the society
      perspective. RESULTS: Most of the patients were men (79%), with a mean age and
      disease duration of 40 and 16 years, respectively. The mean HAQ-S, BASFI and
      BASDAI scores were 1, 5, and 4, respectively. The mean ASQoL score for the sample
      was 8, and the mean Short-Form-36 scores were between 48 (body pain and general
      health) and 81 (emotional role). The average monthly household income for the
      group was US$ 520. The patients had an average of 6 outpatient visits, 6 physical
      therapy visits and 30 laboratory exams per patient, per year. The average total
      cost for society was US$ 4,597 per patient per year, of which 45% were direct
      costs and 55% were indirect costs. CONCLUSIONS: Ankylosing spondylitis is a
      disease that represents a considerable burden to Brazil. It is extremely
      important to carry out studies that assess the costs of chronic diseases,
      especially in developing nations, in order to determine the best manner of
      allocating the already scanty resources in such regions.

PMID- 20810035
TI  - Serum cartilage oligomeric matrix protein (COMP) level is a marker of disease
      activity in relapsing polychondritis.
AB  - OBJECTIVES: Relapsing polychondritis (RP) is a rare and severe disease which may
      lead to destruction of elastic cartilages. Until now, no reliable biomarker of
      disease activity in RP has been available. This study was designed to measure
      serum levels of cartilage biomarkers during both active and inactive phases of
      the disease. METHODS: Serum levels of cartilage oligomeric matrix protein (COMP),
      chondroitin sulfate 846 epitope (CS846) of proteoglycan aggrecan and collagen
      type II collagenase cleavage neoepitope (C2C) were measured retrospectively in 21
      subjects with RP. The Wilcoxon matched-pairs signed-rank test was used for
      statistical comparisons of biomarker levels in active and inactive phases of RP.
      RESULTS: Only the serum level of COMP was significantly increased during disease
      flares. Steroids did not alter the serum cartilage-related biomarker levels.
      However, during the active phase, C2C levels were significantly higher in steroid
      treated patients compared with non-steroid treated patients. CONCLUSIONS: This
      study suggests that serum COMP level may be useful for monitoring disease
      activity of RP. Further prospective studies are required to confirm this result.

PMID- 20810036
TI  - Noonan syndrome and systemic lupus erythematosus in a patient with a novel KRAS
      mutation.
AB  - Noonan syndrome is characterised by distinct facial stigmata, short stature and
      congenital cardiopathy. It has a high genetic heterogeneity and mutations in six
      different genes can be involved. We report a patient with Noonan syndrome and a
      novel KRAS mutation who presents systemic lupus erythematosus.

PMID- 20810037
TI  - Hyper IgM syndrome and complement Clq deficiency in an individual with systemic
      lupus erythematosus-like disease.
AB  - Many immunedeficiency syndromes are associated with autoimmune disorders. We here
      report on a girl with a systemic lupus erythematosus-like disease who suffered
      from both hyperimmunoglobulin M syndrome (HIGMS) and C1q deficiency. Despite
      severe central nervous system-lupus like disease, probably due to C1q deficiency,
      kidney function was relatively spared. IgM autoantibody might play a protective
      role against lupus-glomerulonephritis.

PMID- 20810033
TI  - Gender, body mass index and rheumatoid arthritis disease activity: results from
      the QUEST-RA Study.
AB  - OBJECTIVES: To investigate whether body mass index (BMI), as a proxy for body
      fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific
      manner. METHODS: Consecutive patients with RA were enrolled from 25 countries
      into the QUEST-RA program between 2005 and 2008. Clinical and demographic data
      were collected by treating rheumatologists and by patient self-report.
      Distributions of Disease Activity Scores (DAS28), BMI, age, and disease duration
      were assessed for each country and for the entire dataset; mean values between
      genders were compared using Student's t-tests. An association between BMI and
      DAS28 was investigated using linear regression, adjusting for age, disease
      duration and country. RESULTS: A total of 5,161 RA patients (4,082 women and
      1,079 men) were included in the analyses. Overall, women were younger, had longer
      disease duration, and higher DAS28 scores than men, but BMI was similar between
      genders. The mean DAS28 scores increased with increasing BMI from normal to
      overweight and obese, among women, whereas the opposite trend was observed among
      men. Regression results showed BMI (continuous or categorical) to be associated
      with DAS28. Compared to the normal BMI range, being obese was associated with a
      larger difference in mean DAS28 (0.23, 95% CI: 0.11, 0.34) than being overweight
      (0.12, 95% CI: 0.03, 0.21); being underweight was not associated with disease
      activity. These associations were more pronounced among women, and were not
      explained by any single component of the DAS28. CONCLUSIONS: BMI appears to be
      associated with RA disease activity in women, but not in men.

PMID- 20810039
TI  - Role of endothelial nitric oxide synthase (eNOS) polymorphisms in cardiovascular
      disease and rheumatoid arthritis.

PMID- 20810038
TI  - Condylar lesions in relation to mandibular growth in untreated and intra
      articular corticosteroid-treated experimental temporomandibular joint arthritis.
AB  - OBJECTIVES: To evaluate condylar lesions in relation to mandibular growth in
      experimental temporomandibular joint (TMJ) arthritis and to assess the outcome of
      treating this condition with repeated intra-articular corticosteroid injections
      (IACIs). METHODS: Forty-two 10-week-old rabbits were randomly divided into four
      groups. Seven animals served as controls. Experimental TMJ arthritis was induced
      in five animals which received intra-articular TMJ saline injections. Fifteen
      animals had TMJ arthritis induced and were left untreated and 15 animals had TMJ
      arthritis induced and were treated with IACIs one week after each TMJ antigen
      challenge procedure. Inter-group growth differences were evaluated from head
      computerised tomography scans taken at the time of arthritis induction and 12
      weeks later. The variables assessed were: progression of condylar lesions
      (erosions/flattening/osteophytes), mandibular bone volume changes, condylar and
      sagittal ramus growth. RESULTS: No inter-group differences in the progression of
      condylar lesions were observed despite reduced mandibular growth in all three
      experimental groups. The most pronounced unfavourable mandibular growth
      alterations were observed in the corticosteroid-treated arthritis animals.
      CONCLUSIONS: No evidence was found in support of a relation between reduced
      mandibular growth and condylar lesions. We propose that: 1) condylar lesions are
      not the only causative factor of reduced mandibular growth in experimental TMJ
      arthritis, and 2) repeated IACIs have a very unfavourable impact on mandibular
      growth in experimental TMJ arthritis - treatment is more detrimental to
      mandibular growth than the TMJ arthritis itself.

PMID- 20810041
TI  - Preserved aortic stiffness in Erdheim Chester's coated aorta: a first report.

PMID- 20810042
TI  - Videocapillaroscopy and Marfan syndrome: a 2-case report.

PMID- 20810044
TI  - Challenges of anaesthesia research in developing countries.

PMID- 20810045
TI  - Variability of arch forms in various vertical facial patterns.
AB  - OBJECTIVE: To compare arch forms in various vertical facial patterns and to make
      arch form guides based on posterior intermolar widths. STUDY DESIGN: Cross
      sectional comparative study. PLACE AND DURATION OF STUDY: The Aga Khan University
      Hospital, Karachi, from June 2007 to May 2008. METHODOLOGY: Subjects with age
      range of 13-30 years were selected having full complement of teeth (upto second
      permanent molars) with absence of severe crowding (less than 7 mm). Exclusion
      criteria were presence of dental anomalies, previous dentoalveolar surgery,
      trauma or orthodontic treatment and craniofacial syndromes. One hundred subjects
      including 40 normodivergent, 30 hypodivergent and 30 hyperdivergent cases were
      selected. Occlusograms were made and various arch dimensions were measured. Arch
      forms were calculated according to ratios of three sagittal to three transverse
      dimensions. RESULTS: The mean age of the sample was 21 years and 5 months.
      Differences in arch dimension were found only in maxillary total arch length
      (p=0.03) and mandibular posterior intermolar width (p=0.04). Wide lower arches
      were predominant in all face types. Wide upper arches were predominant in only
      hypo- and hyperdivergent subjects. CONCLUSION: Wide lower arches were predominant
      in all face types whereas wide upper arches were predominant in both hypo- and
      hyperdivergent subjects. A non-linear relationship was found between arch length
      and arch width; so arch form guides could not be made for specific face types.

PMID- 20810046
TI  - Acceptability and accuracy of saline infusion sonohysterography in women with
      postmenopausal bleeding.
AB  - OBJECTIVE: To validate the diagnostic efficacy of saline infusion
      sonohysterography (SIS) in the evaluation of uterine cavity,in women with
      postmenopausal bleeding and endometrial thickness (3) 5 mm. STUDY DESIGN: Cross
      sectional study. PLACE AND DURATION OF STUDY: Military Hospital, Rawalpindi, from
      March 2005 to July 2008 and Combined Military Hospital, Multan, from September
      2008 to June 2009. METHODOLOGY: Seventy seven eligible participants included
      women complaining of postmenopausal bleeding were included; out of whom 69
      completed the procedure satisfactorily. Pain scores during procedure were
      assessed to determine patient acceptability. Following saline infusion
      sonohysterography all patients also underwent an out door pipelle endometrial
      biopsy in a one-stop postmenopausal bleed clinic. Findings of sonohysterography
      were compared with hysteroscopy/hysterectomy specimen. RESULTS: Majority of the
      patients 34 (49.2%) experienced no pain during the procedure, 51 (74%) women had
      a positive SIS and the findings were negative in 18 (26%) patients. The commonest
      abnormal finding on SIS was focal thickening in 23 (32%) and endometrial polyp in
      12 (17%) cases. Saline infusion hysterosonography picked up 3 cases of false
      positive polyps (5.8%) and missed a case of submucous fibroid near cervix (1.8%).
      Upon comparison of findings of hysteroscopy and hysterectomy in 53 cases, there
      was complete agreement in a total of 43 (88%) cases. The sensitivity of
      sonohysterography was 92% and specificity was 78%. All the ladies with abnormal
      SIS had diagnostic or therapeutic procedures and finally only 24 (35%) were
      managed on conservative follow-up. Normal SIS led to conservative management in
      16 (88%). CONCLUSION: Sonohysterography in combination with endometrial biopsy is
      a useful technique useful for the evaluation of postmenopausal bleeding. Patient
      acceptability and diagnostic capability is high and it reduces demand for
      hysteroscopy.

PMID- 20810047
TI  - Clinicopathological features of transient myeloproliferative syndrome and
      congenital leukaemia.
AB  - OBJECTIVE: The objectives of the study were to determine the spectrum of the
      clinical and pathological findings, the management and prognosis of patients of
      transient myeloproliferative syndrome (TMS) and congenital leukaemia. STUDY
      DESIGN: Case series. PLACE AND DURATION OF STUDY: The study was conducted over a
      period of 8 years, from January 2000 to December 2007, at the Children's Hospital
      and the Institute of Child Health, Lahore. METHODOLOGY: Suspected patients
      presenting with fever, pallor, bruises and hepatosplenomegaly and diagnosed as
      either transient myeloproliferative disorder or congenital leukaemia were
      studied. The complete blood count, reticulocyte count, leukocyte alkaline
      phosphatase score, liver function tests, karyotyping studies and bone marrow
      aspiration biopsy were performed in all of those patients. Management and out
      come was noted. Results were described as frequency percentages. RESULTS: Out of
      10,000 patients presenting during this period, 24 patients were diagnosed as
      either of transient myeloproliferative syndrome or congenital leukaemia. Fifteen
      of these were diagnosed as patients of TMS and 9 as patients of congenital
      leukaemia. Down syndrome (DS) was diagnosed in 75% of these patients. TMS
      patients were put on supportive treatment and recovered spontaneously. One DS
      patient with congenital leukaemia went into spontaneous remission and 2 of DS
      patients with congenital leukaemia responded to chemotherapy while rest of them
      either died or lost to follow-up. CONCLUSION: TMS and congenital leukaemia were
      not very uncommon in the studied population. Majority had Down syndrome. It is
      important to differentiate their clinical and pathological presentations for
      proper management. TMS may resolve with supportive treatment while congenital
      leukaemia is a fatal condition requiring chemotherapy.

PMID- 20810049
TI  - Effect of carvedilol on portal pressure estimated by hepatic vein Doppler
      ultrasound waveform and damping index in cirrhotic patients.
AB  - OBJECTIVE: To assess the effect of Carvedilol in reducing portal pressure
      estimated non-invasively by studying Doppler ultrasound waveforms (DUS) and
      hepatic vein Damping Index (DI). STUDY DESIGN: Quasi-experimental study. PLACE
      AND DURATION OF STUDY: Department of Medical ICU in collaboration with Department
      of Radiology, JPMC, over a period of 6 months (June 1st to 30th November, 2008).
      METHODOLOGY: Of the enrolled 65 patients, 47 patients (33 males and 14 females)
      completed the study. The mean age was 47.4 years. Cirrhotic patients of Hepatitis
      B, C, D (delta), B and C combined, B and D combined with varying degrees of
      portal hypertension were included in the study. Cirrhotic patients with bronchial
      asthma, congestive heart failure, Insulin dependent Diabetes, portal vein
      thrombosis and hepatorenal syndrome were excluded from the study. The patients
      were examined by color flow Doppler of the right hepatic vein before and after
      administration of Carvedilol. Their waveforms and Damping Index (DI) were
      recorded and compared by Wilcoxon signed ranks test through SPSS version 12.0.
      Responders were described as those showing a positive change in wave forms or a
      decrese of 0.10 or more in DI. RESULTS: Of the 47 patients, 30 (63%) showed a
      positive response and 10 (21%) showed no favorable response to Carvedilol, while
      7 (14%) patients showed deterioration. The mean DI on DUS dropped from 0.62 to
      0.41 in responders after treatment, while in the non-responders it ranged between
      0.42 and 0.57. CONCLUSION: Ultrasonography Carvedilol reduced portal pressure of
      cirrhotic patients, as measured indirectly by the damping index of hepatic
      waveform by Doppler.

PMID- 20810048
TI  - Treatment profile of hepatitis C patients - a comparison of interferon alpha 2a
      and 2b treatment regimes.
AB  - OBJECTIVE: To compare the side effects, cost, end treatment response (ETR) and
      Sustained viral response (SVR) with combination therapy of either interferon
      alpha 2a or 2b in combination with Ribavarin. STUDY DESIGN: Randomized Control
      Clinical Trial (RCCT). PLACE AND DURATION OF STUDY: The study was conducted at
      Sarwar Zuberi Liver Centre (SZLC), Civil Hospital Karachi (CHK), from May 2004 to
      July 2009. METHODOLOGY: Patients positive for qualitative HCV ribonucleic acid
      (RNA) by Polymerase chain reaction (PCR) and genotype 3 were included. Patients
      with decompensated cirrhosis, severe depressive illness, autoimmune hepatitis,
      hyperthyroidism, pregnancy, heart failure, uncontrolled diabetes, obstructive
      pulmonary disease, children less than three years and patients who had previously
      received treatment were excluded. Single blind randomization using computerized
      randomization list was done and patients divided into groups A and B, those
      requiring treatment were given injection Interferon 3 million units (MU)
      subcutaneously (SC) three times/week and Ribavarin 1000 mg per day (weight <=
      75kg) and 1200 mg/day (weight > 75kg) orally with either interferon alpha 2a
      (group A; FDA approved products) or alpha 2b (group B; non FDA approved product).
      Demographics, side effects, ETR and SVR were noted. ETR was defined as absence of
      virus at the end of treatment and SVR was taken as absence of HCV RNA at 6 months
      after completion of treatment. RESULTS: There were a total 310 patients with mean
      age of 34.07 +/- 9.38 years including 52.4% males, (n=162). Majority of the
      patients were from North Pakistan. There were 155 patients each in group A and
      group B respectively. The cost of treatment for interferon alpha for a single
      patient for 6 months was Rs 60,000, while for Interferon alpha 2b was Rs 30,000.
      Side effects (fever initially, followed by fatigue, headache, musculoskeletal
      pain, depression, alopecia, insomnia, and anorexia) were more prominent in group
      B when compared with group A. In group A, ETR was 83.8% (130/155) while in group
      B was 83.2% (129/155). While SVR available in group A was 61/70 (87.1%) and in
      group B was 60/72 (83.3%). CONCLUSION: Response to combination therapy for HCV
      was 83%. ETR and SVR were similar for both interferon alpha 2a and 2b. Side
      effects though minor are more with alpha 2b (non FDA approved products).

PMID- 20810050
TI  - Age related association of Her-2/neu with prognostic markers in female breast
      carcinoma.
AB  - OBJECTIVE: To determine age-related association of Her-2/neu expression with
      histological and immunohistochemical prognostic markers in female breast
      carcinoma. STUDY DESIGN: Cross sectional, observational study. PLACE AND DURATION
      OF STUDY: Department of Histopathology, Armed Forces Institute of Pathology,
      Rawalpindi, from January 2004 to December 2007. METHODOLOGY: Patients of primary
      operable female breast carcinoma were categorised as < 40 years (pre-menopausal),
      41-50 years (peri-menopausal) and > 50 years (post-menopausal) age groups.
      Histological type, tumour size, tumour grade and lymph node status were
      determined while estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu
      expression were evaluated immunohistochemically. Association of Her-2/neu with
      histological and immnuohistochemical prognostic markers was determined in pre
      menopausal, peri-menopausal and post- menopausal age groups using the x2 test for
      uni- and multivariate analysis. RESULTS: Out of the 722 patients, 230 (31.9%)
      were in pre-menopausal, 221 (30.6%) in peri-menopausal and 271 (37.5%) in post
      menopausal age group. Infiltrating ductal carcinoma was the pre-dominant subtype
      in all the age groups. Mean tumour size was 4.3+/-2.3 cm (range 0.4-17 cm) and
      lymph node metastasis was seen in 310 (70.8%) cases. Her-2/neu showed association
      with ER in the all the age groups while PR only showed association in the peri
      menopausal and postmenopausal women. Her-2/neu showed no association with tumour
      size, tumor grade and lymph node metastases in pre-menopausal and peri-menopausal
      women while it showed positive association with tumour size and lymph node
      metastasis in the post-menopausal women (p < 0.05). CONCLUSION: Majority (62%)
      patients were under 50 years as against the Western epidemiology. Association of
      Her-2/neu with ER, PR, tumour size and lymph node metastasis was age related as
      pre-menopausal, peri-menopausal and postmenopausal had variable expression of
      these prognostic markers with therapeutic and prognostic implications.

PMID- 20810051
TI  - Ophthalmia neonatorum.
AB  - OBJECTIVE: To measure the frequency of ophthalmia neonatorum among all babies
      born in MCH Center, PIMS (Pakistan Institute of Medical Sciences), Islamabad, in
      one month's time and to determine their causative organisms. STUDY DESIGN: An
      observational study. PLACE AND DURATION OF STUDY: The MCH Center, PIMS, during
      the month of November 2008. METHODOLOGY: All babies born from 1st to 30th
      November, 2008 in the MCH Center, PIMS, Islamabad, Pakistan were included in the
      study. All babies were examined for signs of conjunctivitis on days 1, 3, 7, 14,
      21 and 28 of life. Conjunctival swabs were taken for gram staining and culture
      from those with clinical diagnosis of conjunctivitis. Frequency of known maternal
      and neonatal risk factors for the disease were assessed. Proportions were
      compared using chi-square test with significance at p < 0.05. RESULTS: Seventeen
      percent of the 1010 babies developed conjunctivitis. Staphylococcus aureus (65%
      of all positive cultures) was the most common causative organism. No case of
      gonococcus was isolated. Meconium stain liquor (p=0.004) and caesarain section (p
      < 0.001) were found to be the most frequent associated conditions in
      conjunctivitis. CONCLUSION: There was a high frequency of neonatal
      conjunctivitis, with Staphylococcus aureus as the most common causative agent.
      Poor hygienic conditions and practices could be an important risk factor in
      Pakistan.

PMID- 20810052
TI  - Factors predicting the outcome of acute renal failure in pregnancy.
AB  - OBJECTIVE: To determine the factors predicting renal outcome in patients
      developing acute renal failure in pregnancy. STUDY DESIGN: Descriptive cohort
      study. PLACE AND DURATION OF STUDY: Study was conducted at Nephrology Unit of
      Sindh Institute of Urology and Transplantation, Karachi, from October 2006 to
      March 2007. METHODOLOGY: Patients with acute renal failure due to complications
      of pregnancy, with normal size of both the kidneys on ultrasound were enrolled,
      and followed for a period of 60 days or until recovery of renal function.
      Patient's age and parity, presence of antenatal care, type of complication of
      pregnancy, foetal outcome and duration of oliguria were compared between patients
      who remained dialysis dependent and those who recovered renal function. Chi
      square/Fisher's exact test and student's t-test, were used for determining the
      association of categorical and continuous variables with dialysis dependency.
      RESULTS: The mean age was 29+/-6 years. Most patients came from rural areas of
      interior Sindh. Sixty eight percent did not have antenatal checkups. Antepartum
      haemorrhage (p=0.002) and prolonged duration of oliguria (35+/-15.7 days, p= <
      0.001) were associated with dialysis dependency, which was observed in 50% of the
      study group. CONCLUSION: Ante-partum haemorrhage and prolonged oliguria were
      strong predictors of irreversible renal failure. This highlights the need for
      early recognition and referral, and the importance of trained birth attendants
      and antenatal care.

PMID- 20810053
TI  - Etiological diagnosis of microbial keratitis.
AB  - OBJECTIVE: To identify the different microbial pathogens in infective corneal
      ulcers. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY:
      Department of Ophthalmology Unit I, Eye Hospital, Liaquat University of Medical
      and Health Sciences, Hyderabad, Sindh, from April 2006 to September 2008.
      METHODOLOGY: Patients above 15 years of age with suspected infective corneal
      ulcers were studied. After detailed history every patient underwent a
      comprehensive ophthalmic slit lamp bio-microscopical examination, for
      characteristics of the ulcer to locate the site, size, depth of ulcer and
      anterior chamber inflammation. After a detailed ocular examination corneal
      scrapings were collected under aseptic conditions under magnification of slit
      lamp or operating microscope. The scraping material obtained from leading edge
      and base of each ulcer was spread onto labeled slides for staining. Another
      portion was inoculated on to the surface of solid and the liquid culture medias.
      The inoculated medias were incubated at appropriate temperature for appropriate
      time. RESULTS: Of the 328 patients; 192 (64.99%) were male with age ranging from
      15 to 80 years, and majority from rural population (64.99%). Majority i.e. 201
      (61.28%) were previously treated. Out of 328 patients, 161 cultured (49.10%) for
      bacteria, 87 (26.52%) for fungi, and 12 were found positive culture for both
      bacteria and fungi. The rest of 68 (20.73%) were culture-negative corneal ulcers.
      Of the 173 bacterial isolates, 119 (68.79%) had Gram positive cocci, most common
      isolated being Staphylococcus aureus in 82 (47.40%); fungal pathogens were
      isolated from 99 corneal ulcers. The commonest organism isolated was Candida
      albicans in 75.76%, followed by Aspergillus flavus in 11.11% of the total fungal
      isolates. CONCLUSION: Staphylococcus aureus, Candida albicans and Aspergillus
      flavus were common causes of microbial infective keratitis in this series.

PMID- 20810054
TI  - Pattern of drugs of abuse identified in chemical samples.
AB  - OBJECTIVE: To determine the pattern of drugs of abuse in urine and blood samples
      processed at referral laboratory in Pakistan so that information on the type of
      drugs used can be identified and used for ready reference for future strategy.
      STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Clinical
      Laboratory of The Aga Khan University Hospital, Karachi, from July 2006 to March
      2008. METHODOLOGY: Retrospective review of records were done for the common drugs
      that are used for screening at the Clinical Laboratory include alcohol,
      amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates.
      Alcohol was tested in blood and others were identified using urine. Percentages
      of tests screened positive and negative for individual drugs were computed by
      using SPSS 16.0. The ratio between male and female users was also established.
      RESULTS: A total of 17,714 tests were performed for drugs. The mean age of the
      patients whose samples were processed was 30+/-14.84 years. Majority used
      benzodiazepines 520/1317 (39.5%) among the samples tested for drug of abuse,
      followed by cannabinoids 423/5450 (7.8%), alcohol 75/1302 (5.8%), barbiturates
      32/1148 (2.8%), opiates 137/5640 (2.4%), cocaine 5/1655 (0.3%) and amphetamine
      3/1202 (0.2%). In all, males 15411 (87%) were tested more frequently as compared
      to females 2303 (13%). CONCLUSION: Males were more frequently tested for drug
      abuse; however, drug abuse is increasingly seen among females. Benzodiazepines
      are the most frequently used. The same pattern of drugs abuse existed in
      different gender and age group. There is a need to explore the pattern and type
      of drug abuse on national scale.

PMID- 20810055
TI  - Percutaneous cholecystostomy (PC) in the management of acute cholecystitis in
      high risk patients.
AB  - OBJECTIVE: To determine the role of ultrasound-guided percutaneous
      cholecystostomy (PC) regarding complications and outcome in the management of
      acute cholecystitis in patients high risk for surgery and anaesthesia and not
      responding to conservative management. STUDY DESIGN: Observational case series.
      PLACE AND DURATION OF STUDY: The study was carried out at The Aga Khan University
      Hospital, Karachi, from January 2003 to December 2007. METHODOLOGY: The study
      included patients admitted with acute cholecystitis considered unfit for
      immediate surgery but not responding to conservative management. Percutaneous
      cholecystostomy was conducted under ultrasound guidance. The studied variables
      included patients' demographics, co-morbid, ultrasound findings of biliary tree,
      indication for percutaneous cholecystostomy, its route, complication during or
      after procedure, patient's clinical outcome (upto 48 hours) and 30 days follow
      up. Those with incomplete medical record and follow-up were excluded. Data were
      analyzed and results compiled using SPSS 16.0 version. Mean and standard
      deviation for quantitative variable like age was derived. Proportions were
      computed for complications and patient's clinical outcome. RESULTS: Forty one
      patients with complete medical record were studied including 15 (37%) males and
      26 (63%) females. Mean age was 65 +/-13.5 years. Indications for PC included
      calculus cholecystitis in 25, acalculous cholecystitis in 10, empyema in 04 and
      gallbladder perforation in 02 patients. No complication was seen during or after
      procedure in 31 (75%) patients. Complications occurred in 10 (25%) patients
      including vagal reaction, pain during procedure, tube blockage, catheter
      dislodgement and bile leakage. Favourable clinical response (improvement in
      clinical symptoms) was noted in 34 (83%) patients. Seven (17%) patients did not
      show any improvement in clinical condition after the procedure. On 30 days follow
      up, 9 patients had undergone cholecystectomy, 5 (12%) patients expired due to
      underlying clinical conditions and the rest were settled without requiring an
      immediate cholecystectomy. There was no direct procedure-related mortality.
      CONCLUSION: Imaging guided PC is a safe and effective procedure for immediate
      management of non-resolving acute cholecystitis in patients high risk for surgery
      and anaesthesia and not responding to conservative management.

PMID- 20810056
TI  - Rare presentation of biliary ascariasis.
AB  - Ascariasis is the most common helminthic infection in the world. We present a
      very rare manifestation of ascariasis in which the worms came out through the T
      tube tract of a 36 years old patient who had undergone cholecystectomy with
      choledocholithotomy.

PMID- 20810057
TI  - Gastrointestinal stromal tumour in a young adult.
AB  - Gastrointestinal stromal tumour (GIST) is a type of tumour that occurs in
      gastrointestinal (GI) tract, and arises from stroma with no definite cell line of
      origin and varying pattern of differentiation. It is a type of soft tissue
      sarcomas. We report a case of a young adult female who was diagnosed with GIST
      which was found to be unresectable at surgery and was subsequently managed with
      Imatinib. Treatment with the drug has led to a significant improvement for about
      2 years.

PMID- 20810058
TI  - Laparoscopic excision of heterotopic pancreas of stomach.
AB  - Heterotopic pancreas (HP) in stomach is a rare pathological entity that poses
      clinical dilemma for diagnosis and management. It carries a risk of developing
      serious benign and malignant complications. This is a case of 37-year-old lady
      who presented with dyspeptic symptoms and was found to have a 1.5 cm umblicated
      lesion in the distal stomach on gastroscopy. Endoscopic biopsy showed normal
      gastric mucosa and CT scan of stomach did not show any specific abnormality. A
      laparoscopic wedge excision was performed. Histology showed features of
      heterotopic pancreas. Endoscopic and histological pictures are presented to
      increase the awareness of this rare entity. Laparoscopic wedge excision's of a
      localized HP is recommended as a safe procedure to achieve diagnosis and plan for
      further management.

PMID- 20810059
TI  - Spontaneous resolution of direct carotid cavernous fistula.
AB  - Proptosis due to carotid cavernous fistula is rare sequelae of head injury. We
      report a case of post-traumatic, direct high flow carotid cavernous fistula that
      resolved spontaneously 06 weeks after carotid angiography. It however, resulted
      in loss of vision due to delay in early treatment. In the cases of post-traumatic
      proptosis, carotid cavernous fistula should be kept in mind.

PMID- 20810060
TI  - Primary pulmonary hypertension with retinal neovascularization.
AB  - A middle aged lady presented with gradual increase in shortness of breath and
      reduced vision bilaterally. The patient had no history of Diabetes mellitus,
      hypertension or any other co-morbid illness. Examination revealed signs of right
      sided heart failure, pulmonary hypertension and neovascularization of retina.
      Echocardiography confirmed pulmonary hypertension and fluorescence angiography
      confirmed neovascularization of retina. Treatment with Sildenafil resulted in
      symptomatic improvement.

PMID- 20810062
TI  - Complicated megaureter with aganglionosis in an adult lady.
AB  - Dilated ureters are often due to mechanical obstruction. This case report
      describes a young adult lady with primary megaureter due to aganglionosis finally
      managed with extravesical Leech-Gregor Uretroneocystostomy.

PMID- 20810061
TI  - Johanson-Blizzard syndrome with Diamond-Blackfan anemia.
AB  - Johanson Blizzard syndrome (JBS) is a rare multi-system disorder characterized by
      congenital aplasia or hypoplasia of alae nasi, exocrine pancreatic insufficiency,
      hypothyroidism, deafness, growth retardation, varying degree of mental
      retardation, alopecia, wide open fontanels, anti-mongoloid slant, cafe-au-lait
      spots and absent of permanent teeth. We report a 3 months old male child having
      Johanson Blizzard syndrome with classical clinical features, pancreatic
      insufficiency and Diamond-Blackfan anemia.

PMID- 20810063
TI  - Cardiac surgery in octogenarians.
AB  - In Europe and North America, cardiac surgery can be done successfully on
      octogenarians, but differences in patient selection, surgical and bypass
      techniques prevent us from concluding similarly in Pakistan. This study
      investigated the short and long-term outcomes of cardiac surgery in octogenarians
      operated over a 5 years period at The Aga Khan University Hospital, from January
      2001 to December 2006. Seventeen octogenarians, (mean age 81.7 +/- 2.3) underwent
      coronary artery bypass graft (CABG). Thirty-days hospital mortality was reported
      in only 1 patient. Surgical complication of any kind was reported in 13 (76.5%)
      patients with pleural effusion being the commonest in hospital complication seen
      in 11 (64.7%) patients. About 13 (92.9%) patients were satisfied with the results
      of the surgery and reported post-surgery improvement in quality of their life.
      Cardiac surgery has an important role in the management of elderly patients with
      medically refractory cardiac symptoms, but the implications of widespread cardiac
      surgery in the elderly need to be addressed.

PMID- 20810064
TI  - ECG changes in a patient with essential tremors.

PMID- 20810065
TI  - Nuclear imaging for screening coronary artery disease in diabetics.

PMID- 20810066
TI  - Pharmageddon on obesity.

PMID- 20810067
TI  - Information overload: technology, the internet, and arthroscopy.

PMID- 20810068
TI  - Growth factor confusion.

PMID- 20810072
TI  - Computer-simulation training for arthroscopic surgery: what is to be considered?

PMID- 20810073
TI  - Anteromedial portal drilling for anatomic anterior cruciate ligament
      reconstruction.

PMID- 20810075
TI  - Interscalene block for shoulder surgery in physician-owned community ambulatory
      surgery centers.
AB  - PURPOSE: To retrospectively report on a series of patients who had interscalene
      block regional anesthesia performed for outpatient open and arthroscopic shoulder
      surgical procedures in a community-based ambulatory surgery center setting.
      METHODS: We reviewed the cases of 1,945 patients who had interscalene block
      regional anesthesia performed during an 8-year period. RESULTS: The complication
      rate was 0.63%, with all complications occurring in the immediate postoperative
      period, none of which were permanent. CONCLUSIONS: With an expert, experienced
      anesthesia team, the interscalene block can be a safe method (temporary
      complication rate, 0.63%) of intraoperative anesthesia and perioperative
      analgesia for outpatient open and arthroscopic shoulder surgery in physician
      owned ambulatory surgery centers. LEVEL OF EVIDENCE: Level IV, therapeutic case
      series.

PMID- 20810076
TI  - A biomechanical analysis of the native coracoclavicular ligaments and their
      influence on a new reconstruction using a coracoid tunnel and free tendon graft.
AB  - PURPOSE: To understand and characterize the kinematic properties of the 2
      coracoclavicular ligaments and to evaluate the biomechanical performance of a new
      3-tunnel reconstruction of the coracoclavicular ligaments by use of a free tendon
      graft. METHODS: Ten fresh-frozen cadaveric shoulders were tested. The kinematics
      and in situ forces of the coracoclavicular ligaments were tested with a robotic
      testing system. Kinematics of the shoulder in the intact state, in the sectioned
      state, and finally, after a coracoclavicular reconstruction and a
      coracoclavicular sling reconstruction were evaluated. RESULTS: The conoid had
      higher in situ forces during anterior and superior loading of the clavicle when
      compared with the trapezoid ligament, whereas the trapezoid ligament had higher
      in situ forces during posterior loading. Sectioning the trapezoid ligament
      significantly increased translation of the clavicle in the posterior direction,
      whereas sectioning the conoid ligament significantly increased superior
      translation. When we compared the 2 reconstruction techniques, the coracoid
      tunnel reconstruction was superior in controlling anterior translation whereas
      the coracoclavicular sling reconstruction was inferior because of anterior
      displacement of the graft. There was no significant difference in posterior or
      superior translation between either reconstruction technique. CONCLUSIONS: The
      trapezoid and conoid ligaments have unique functions in normal shoulder
      kinematics because of their anatomic attachments. By more faithfully restoring
      these insertion sites on the clavicle and controlling motion of the graft on the
      coracoid, the 3-tunnel reconstruction technique more closely restores native
      shoulder kinematics than the coracoclavicular sling technique. CLINICAL
      RELEVANCE: Understanding the unique roles of the conoid and trapezoid bundles of
      the coracoclavicular ligament may improve surgical techniques in the management
      of acromioclavicular joint injuries. The reconstructive technique presented more
      faithfully restores normal kinematics and forces across the acromioclavicular
      joint than the coracoclavicular sling technique.

PMID- 20810077
TI  - Arthroscopic posterior stabilization and anterior capsular plication for
      recurrent posterior glenohumeral instability.
AB  - PURPOSE: The purpose of this study was to evaluate the outcomes and identify
      predictors of success for arthroscopic posterior Bankart reconstruction with
      modern suture anchor repair and anterior capsulolabral plication in a well
      defined patient population-recurrent, traumatic, involuntary, unidirectional
      posterior shoulder instability. METHODS: Patients with recurrent, traumatic,
      involuntary, unidirectional posterior shoulder instability who underwent
      arthroscopic repair with a minimum of 2 years' follow-up were identified and
      evaluated retrospectively with outcome measures in the form of objective and
      subjective scores. Statistical analysis was performed to identify predictors of
      success with significance set at .05. RESULTS: Twenty-nine consecutive patients
      with a mean age of 26.3 years underwent posterior reconstruction and anterior
      balancing capsulolabral plication as needed with a mean follow-up of 5.5 years.
      Outcome scores averaged as follows: American Shoulder and Elbow Surgeons, 90.7;
      University of California, Los Angeles, 32.6; Simple Shoulder Test, 11.7; and
      Western Ontario Shoulder Instability, 82.9% of normal. Recurrent instability
      occurred in 3.4% of patients, 84.6% returned to sports, and 96.6% of patients
      believed surgery was successful and worthwhile. Patients who were younger (<30
      years) or patients with more extensive pathology who required additional surgical
      procedures or received supplemental anterior plication sutures had less reliable
      or worse outcomes (P < or = .041). CONCLUSIONS: In a traumatic patient population
      with involuntary, unidirectional posterior shoulder instability, modern suture
      anchor repair of posterior labral lesions is effective and provides reliable
      outcomes. Younger patients and patients with worse pathology who required
      additional procedures had less reliable outcomes. Patients with supplemental
      anterior plication had more postoperative pain, and this adjunctive procedure may
      not be necessary for traumatic posterior labral tear surgery. LEVEL OF EVIDENCE:
      Level IV, therapeutic case series.

PMID- 20810078
TI  - Intraoperative comparison of knee laxity between anterior cruciate ligament
      reconstructed knee and contralateral stable knee using navigation system.
AB  - PURPOSE: The objective of this study was to compare knee laxity between anterior
      cruciate ligament (ACL)-reconstructed knees and contralateral stable knees by use
      of intraoperative navigation. METHODS: Five patients with ipsilateral ACL
      deficient knees with contralateral stable knees without any ligament injuries
      were included in this study. Anteroposterior (AP) knee laxity during anterior
      drawer force applied manually and range of tibial rotation and AP knee laxity
      during internal and external rotational torque applied manually in both the ACL
      deficient knee and the contralateral stable knee were measured by use of a
      navigation system from 15 degrees to 90 degrees of knee flexion. After the
      temporary fixation of the posterolateral bundle, anteromedial bundle (AMB), or
      double-bundle (DB) reconstruction, knee laxity was measured again and compared
      with that of the stable knee. RESULTS: The mean laxities for PLB reconstruction
      were significantly greater than those of the contralateral stable knee at more
      than 75 degrees of knee flexion (P < .05). The mean laxities for AMB or DB
      reconstruction were not significantly different from those of the contralateral
      stable knee at all knee flexion angles. Those for AMB reconstruction were within
      +1.6 mm and those for DB reconstruction were within -2.0 mm of those of the
      contralateral stable knee. The mean rotations for all reconstructions were
      significantly less than those of the contralateral stable knee at less than 30
      degrees of knee flexion (P < .05). CONCLUSIONS: DB and AMB reconstructions could
      restore knee laxity closer to the level of the contralateral stable knee. Because
      normal knee laxity is different in each individual, evaluation of contralateral
      stable knee laxity during ACL reconstruction surgery would be helpful for
      restoration to the level of the specific preinjury knee laxity. LEVEL OF
      EVIDENCE: Level IV, therapeutic case series.

PMID- 20810079
TI  - Lower extremity compensatory neuromuscular and biomechanical adaptations 2 to 11
      years after anterior cruciate ligament reconstruction.
AB  - PURPOSE: To determine whether compensatory neuromuscular and biomechanical
      adaptations exist after successful anterior cruciate ligament reconstruction and
      rehabilitation. METHODS: Seventy subjects, 5.3 +/- 3 years after surgery,
      participated in this study. Sagittal-plane lower extremity kinematic, gluteus
      maximus, vastus medialis, medial hamstring, and gastrocnemius electromyography
      (EMG) and vertical ground reaction force data were collected during single-leg
      countermovement jump (CMJ) performance. RESULTS: Women had lower propulsive and
      landing forces, lower CMJ heights, less hip and knee flexion, and greater angular
      hip, knee, and ankle velocities than men (P < or = .014). The involved lower
      extremity of men and women had decreased landing forces (P = .008). During
      propulsion, men and women had increased involved-lower extremity gluteus maximus
      (P < .0001) and decreased vastus medialis (P = .013) EMG amplitudes, whereas
      women had bilaterally increased gastrocnemius EMG amplitudes compared with men (P
      = .003). During propulsion, men had longer gluteus maximus and vastus medialis
      EMG durations than women (P < .0001). During landing, both men and women had
      increased gluteus maximus EMG amplitudes at the involved lower extremity (P <
      .0001). Women had increased vastus medialis (P = .01) and gastrocnemius (P <
      .0001) EMG amplitudes compared with men. During landing, men had longer gluteus
      maximus (P = .004), vastus medialis (P = .012), and gastrocnemius (P = .007) EMG
      durations than women and the involved-lower extremity vastus medialis EMG
      durations of both men and women were shorter than at the noninvolved lower
      extremity (P = .011). CONCLUSIONS: Decreased involved-lower extremity landing
      forces, decreased vastus medialis activation, and increased gluteus maximus and
      gastrocnemius activation suggest a protective mechanism to minimize knee loads
      that increase anterior translatory knee forces during single-leg jumping. Women
      showed more balanced gluteus maximus, vastus medialis, and gastrocnemius
      contributions to dynamic knee stability than men during CMJ landings but used
      shorter activation durations. LEVEL OF EVIDENCE: Level IV, therapeutic case
      series.

PMID- 20810080
TI  - Elbow arthroscopy: a new technique.

PMID- 20810081
TI  - Osseous deficits after anterior cruciate ligament injury and reconstruction: a
      systematic literature review with suggestions to improve osseous homeostasis.
AB  - PURPOSE: This systematic review was performed to improve our understanding of the
      current evidence regarding the influence of anterior cruciate ligament (ACL)
      injury and reconstruction on involved lower extremity apparent bone mineral
      density, bone content, or bone area mass (bone integrity). METHODS: Two
      independent reviewers performed a Medline search from 1966 to January 2010 using
      the terms "anterior cruciate ligament" or "ACL" combined with "wound" or "injury"
      and "bone density" or "osteoporosis." Study inclusion criteria were English
      language human studies. Reference sections of selected studies were also
      reviewed. RESULTS: Ten studies were identified that met our inclusion criteria.
      Eight studies performed ACL reconstruction with bone-patellar tendon-bone
      autografts and interference screw fixation. One study performed ACL
      reconstruction by use of Achilles tendon allografts with interference screw and
      staple fixation. Two ACL injury studies either did not involve ACL reconstruction
      or attempted primary repair with sutures. All studies reported varying levels of
      decreased bone mineral density, bone content, or bone area mass (bone integrity)
      at the involved lower extremity after ACL injury that did not return to premorbid
      levels even with ACL reconstruction and rehabilitation. Sites of reduced bone
      integrity included the proximal and distal femur, proximal tibia, patella, and
      calcaneus. Bone loss was increased with limited weight bearing and prolonged
      disuse or immobilization; however, significant improvements were not observed
      with accelerated rehabilitation. Some studies reported relations between Lysholm,
      Tegner, International Knee Documentation Committee survey, or function scores and
      bone integrity, whereas others reported no or poor relations. CONCLUSIONS:
      Involved lower extremity bone integrity is decreased after ACL injury. Current
      evidence suggests that premorbid bone integrity is not re-established after ACL
      reconstruction even when accelerated rehabilitation is performed. Recommendations
      to improve osseous homeostasis and bone health after ACL injury and
      reconstruction are provided.

PMID- 20810082
TI  - Simultaneous reconstruction of ruptured anterior cruciate ligament and medial
      patellofemoral ligament with ipsilateral quadriceps grafts.
AB  - Rupture of the anterior cruciate ligament is a well-known entity and causes
      anteroposterior and rotational instability of an injured knee. Rupture of the
      medial patellofemoral ligament is less frequent, and its insufficiency causes
      patellar instability. Several techniques have been described for the
      reconstruction of each ligament. The 2 lesions and following instabilities can
      coexist, and both ligaments can be reconstructed simultaneously. We report on 2
      cases, 1 recreational sportswoman and 1 high-level sportswoman, with coexisting
      lesions treated surgically by a single-step procedure using ipsilateral graft of
      the quadriceps tendon for reconstruction of medial patellofemoral ligament and
      anterior cruciate ligament. The advantage of this procedure is that there is only
      1 donor site, and thus lower donor-site morbidity, while the strength of either
      neoligament is not sacrificed. The technique is described here.

PMID- 20810083
TI  - Glenoid avulsion of the glenohumeral ligaments as a cause of recurrent anterior
      shoulder instability.
AB  - Although the Bankart lesion is accepted as the primary pathology responsible for
      recurrent shoulder instability, recognition of other soft-tissue lesions has
      improved the surgical treatment for this common problem. Whereas humeral avulsion
      of the glenohumeral ligaments has been acknowledged as a cause of anterior
      shoulder instability, we have not found any reported cases of glenoid avulsion of
      the glenohumeral ligaments. We describe 3 cases of recurrent anterior shoulder
      instability due to glenoid avulsion of the glenohumeral ligaments. The avulsed
      ligaments were repaired to the labrum and glenoid, restoring the glenohumeral
      ligament-labral complex.

PMID- 20810085
TI  - Can gabapentin help reduce postoperative pain in arthroscopic rotator cuff
      repair? A prospective, randomized, double-blind study.
AB  - PURPOSE: The aim of the study was to determine the effect of low-dose gabapentin
      on postoperative pain management in patients undergoing arthroscopic rotator cuff
      repair. METHODS: This randomized, double-blinded, placebo-controlled study
      included 46 patients. The patients were divided into 2 groups according to the
      drug administered 2 hours before surgery, either 300 mg of gabapentin or placebo.
      The primary outcome measure was the visual analog scale (VAS) score at 2, 6, 12,
      and 24 hours postoperatively. The secondary outcome measures were fentanyl
      consumption and side effects during the first 2 hours in the postanesthesia care
      unit and then at 6 and 24 hours postoperatively. The patients were evaluated for
      side effects including nausea, vomiting, respiratory depression, dizziness,
      drowsiness, voiding difficulty, and pruritus. RESULTS: The VAS scores at 2, 6,
      and 12 hours postoperatively were significantly lower in the gabapentin group
      than in the placebo group (P = .023, P = .019, and P = .022, respectively). The
      consumption of fentanyl, over a period of 24 hours, was not different in the
      comparisons between the groups (P = .686). The incidence of side effects was
      similar in the 2 groups. CONCLUSIONS: A single dose of 300 mg of gabapentin
      reduced the VAS score during the first 24 hours postoperatively in patients
      undergoing shoulder arthroscopic rotator cuff repair, without significant side
      effects when compared with placebo. However, the fentanyl consumption did not
      differ between the gabapentin and placebo groups. LEVEL OF EVIDENCE: Level I,
      randomized controlled trial.

PMID- 20810086
TI  - A comparison of knot security and loop security in arthroscopic knots tied with
      newer high-strength suture materials.
AB  - PURPOSE: The purpose of this study was to compare the knot security and loop
      security of 2 sliding and 1 static arthroscopic knot tied with different types of
      suture material. METHODS: We evaluated 3 commonly used arthroscopic knots
      (surgeon's knot, Roeder knot, and Weston knot) tied with 6 different braided No.
      2 sutures (FiberWire [Arthrex, Naples, FL]; Ethibond [Ethicon, Somerville, NJ];
      Orthocord [DePuy Mitek, Raynham, MA]; Herculine [now called HiFi; ConMed
      Linvatec, Largo, FL]; MaxBraid [Arthrotek, Warsaw, IN]; and UltraBraid [Smith &
      Nephew, Andover, MA]). Each suture loop was then mounted on a materials testing
      system, and its circumference was measured at a 5-N preload to assess each knot's
      ability to maintain a tight suture loop without slippage (loop security). Knot
      security was measured as the maximum force to failure at 3 mm of crosshead
      displacement or suture breakage during single-pull load testing. RESULTS: We
      found that tying knots with different types of suture material can affect both
      the knot security and loop security of various types of arthroscopic knots. When
      a Roeder knot or surgeon's knot was tied, No. 2 FiberWire had the highest force
      to failure when compared with similar knots tied with other suture material (P <
      .001). The loop security for many of the knot and suture configurations was not
      significantly different. However, No. 2 FiberWire consistently showed the
      smallest loop circumference when compared with other suture materials.
      CONCLUSIONS: Arthroscopic knots tied with No. 2 FiberWire provide superior knot
      security and similar loop security compared with other commonly used high
      strength polyethylene suture materials. CLINICAL RELEVANCE: High-strength sutures
      exhibit unique mechanical characteristics that may vary significantly between
      suture types. In addition, knot configuration plays an important role in altering
      these characteristics as they relate to knot security.

PMID- 20810087
TI  - Comparison of mechanical stability in double-row rotator cuff repairs between a
      knotless transtendon construct versus the addition of medial knots.
AB  - PURPOSE: Our purpose was to investigate the importance of medial-row knot tying
      to mechanical stability in a double-row rotator cuff repair by comparing a
      knotless construct with transtendon anchor passage versus a similar construct
      implementing medial knots. METHODS: A standard defect was created in the
      infraspinatus tendons of 14 bovine humeri. All defects were repaired with 2
      medial and 2 lateral anchors (SutureCross System; KFx Medical, Carlsbad, CA). The
      medial anchors were either placed by transtendon passage in a knotless construct
      or placed directly into bone with needle passage of suture to create bursal-sided
      knots medially. Constructs were subjected to a cyclic loading protocol and then
      loaded to failure. RESULTS: The medially knotted constructs had a statistically
      higher stiffness at both the initial and final cycles (P < .001 and P < .001,
      respectively) and a lower displacement during cyclic loading (P < .02). There
      were strong trends toward decreased gauge displacement (P = .12) and decreased
      cycles to 3 mm of displacement (P = .07) in the medially knotted group. Maximal
      yield strength was greater in the medially knotted group (350 +/- 270 N v 650 +/-
      530 N), although this was not found to be statistically significant (P = .5).
      CONCLUSIONS: Our data suggest that creation of medial knots increases construct
      stiffness and stability in arthroscopic double-row cuff repair. This is likely
      because of increased load transfer to the lateral anchor and suture-tendon
      interface in the knotless construct. CLINICAL RELEVANCE: Medial knots create
      increased mechanical stability that theoretically may improve rotator cuff
      healing. This mechanical advantage must be weighed against surgical efficiency,
      with consideration given to factors such as tissue quality.

PMID- 20810088
TI  - Comparative testing by cyclic loading of rotator cuff suture anchors containing
      multiple high-strength sutures.
AB  - PURPOSE: To compare isolated medial-row with isolated lateral-row anchor
      performance by use of cyclic loading followed by destructive testing in an in
      vitro cadaveric model. METHODS: Using 16 human cadaveric humeri without tendons,
      we rotated 4 medial-row (Bio-Corkscrew FT [Arthrex, Naples FL], CrossFT PK
      [ConMed Linvatec, Largo, FL], TwinFix PK FT [Smith & Nephew Endoscopy, Andover,
      MA], and Healix PK [DePuy Mitek, Raynham, MA]) and 4 lateral-row (PopLok PK
      [ConMed Linvatec], PEEK [polyetheretherketone] PushLock [Arthrex], Footprint PEEK
      [Smith & Nephew Endoscopy], and Versalok [DePuy Mitek]) anchors among different
      medial (articular cartilage edge) and lateral greater tuberosity sites (anterior,
      central, posterior). All medial anchors were inserted into the humeral head at an
      angle no greater than 45 degrees . All lateral anchors were inserted "over the
      top," nearly planar to the superior humeral surface. After preloading, the
      constructs were cycled 500 times from 10 to 60 N at 1 Hz with the loads applied
      to the accompanying sutures. Those constructs surviving cycling were
      destructively tested. Cyclic displacement, ultimate load, and failure mode were
      recorded. RESULTS: In this laboratory setting, most displacement occurred in the
      first 100 cycles except for the Footprint anchor. Lateral-row anchors had greater
      mean displacements (2.6 mm) than medial-row anchors (1.2 mm) at 100 cycles and
      between 100 and 500 cycles (1.8 mm v 0.75 mm). Lateral-row anchors also had more
      total displacement (4.4 mm) than medial-row anchors (1.9 mm). A 5-mm displacement
      gap, defined as failure, was not seen in the Bio-Corkscrew FT, TwinFix PK FT, and
      Versalok anchors. Ultimate failure loads ranged from 163 N (Footprint) to 308 N
      (Versalok) (P < .05). The principal failure mode was anchor pullout, followed by
      eyelet breakage. Medial-row eyelet failures only occurred after 500 cycles at
      loads higher than each anchor's mean failure load. Eyelet failure for lateral-row
      anchors occurred before 500 cycles and at failure loads lower than each anchor's
      mean. CONCLUSIONS: Lateral row anchors benefit from medial row anchors for their
      security, and because of design differences demonstrate more displacement. When
      lateral-row anchors fail at the eyelet, it is at lower failure loads, while if
      medial-row anchors fail at the eyelet, it is at higher loads. CLINICAL RELEVANCE:
      Anchors designed to function as lateral-row fixation provide fixation strength
      inferior to that of medial-row anchors and are more likely to be subject to
      suture slippage.

PMID- 20810089
TI  - Severe cerebral desaturation during shoulder arthroscopy in the beach-chair
      position.
AB  - During shoulder arthroscopy in the beach-chair position, cerebral ischemia may be
      a serious complication because prolonged hypotension may affect regional cerebral
      oxygen supply. We present the cases of 2 patients in whom a reduction in mean
      arterial pressure after anesthesia provoked a decrease in frontal lobe
      oxygenation to below the level that causes presyncopal symptoms in the awake
      subject. In the healthy middle-aged patient, cerebral oxygenation decreased by
      approximately 40%, indicating that cerebral blood flow was markedly reduced, and
      intravenous administration of ephedrine rapidly restored cerebral oxygenation.
      During surgery in the beach-chair position, hypotension must be avoided, and in
      all patients regional, cerebral oxygenation should be monitored and optimized.

PMID- 20810090
TI  - "Anatomic" anterior cruciate ligament reconstruction: a systematic review of
      surgical techniques and reporting of surgical data.
AB  - PURPOSE: The aim of this systematic review was to evaluate studies published on
      anatomic double-bundle anterior cruciate ligament (ACL) reconstruction. METHODS:
      A systematic electronic search was performed by use of the Medline and Embase
      databases. Studies that were published from January 1995 to April 2009 were
      included. The selection criteria were studies that reported on a surgical
      technique for "anatomic double-bundle ACL reconstruction" on skeletally mature
      living human subjects and were written in English. Data collected and analyzed
      included a variety of surgical data. Tables were created to provide an overview
      of surgical techniques for anatomic ACL reconstruction. RESULTS: Seventy-four
      studies were included in this review. Some surgical factors were adequately
      reported in the majority of the articles: visualizing the native ACL insertion
      sites, placing the tunnels in the footprint, graft type, and fixation method.
      However; ACL insertion site measurement, femoral intercondylar notch measurement,
      individualization of surgery, and intraoperative/postoperative imaging were
      poorly reported. The most variety was seen in knee flexion angle during femoral
      tunnel drilling and tensioning pattern of the grafts. CONCLUSIONS: For most
      surgical data, there was a gross under-reporting of specific operative technique
      data. We believe that the details of an "anatomic" operative technique are
      crucial for the valid interpretations of the outcomes. Thus we encourage authors
      to report their surgical technique in a specific and standardized fashion.

PMID- 20810091
TI  - Anatomic double-bundle anterior cruciate ligament reconstruction.
AB  - Several double-bundle anterior cruciate ligament (ACL) reconstruction procedures
      were reported in the 1980s and 1990s. However, no significant differences were
      found in the clinical results between these double-bundle procedures and single
      bundle procedures because the double-bundle procedures appeared to reconstruct
      only the anteromedial bundle with 2 bundles. In the early 2000s, we proposed a
      new concept of anatomic reconstruction of the anteromedial and posterolateral
      bundles, in which 4 independent tunnels were created through the center of each
      anatomic attachment of the 2 bundles. We called it "anatomic" double-bundle ACL
      reconstruction. Biomechanical studies have shown that the anatomic double-bundle
      ACL reconstruction can restore knee stability significantly more closely to the
      normal level than the conventional single-bundle reconstruction. Recent
      intraoperative measurement studies have shown that the clinically available
      anatomic double-bundle procedures can reconstruct knee stability significantly
      better and improve knee function close to the normal level at the time
      immediately after surgery compared with the conventional single-bundle
      procedures. However, the greatest criticism of the anatomic double-bundle
      reconstruction is whether its clinical results are better than the results of
      single-bundle reconstruction. To date (January 2010), 10 prospective comparative
      clinical trials (Level I or II) and 1 meta-analysis have been reported comparing
      single-bundle and anatomic double-bundle reconstructions using hamstring tendons.
      In 8 of the 10 studies, the anterior and/or rotatory stability of the knee was
      significantly better with the anatomic double-bundle ACL reconstruction than with
      the conventional single-bundle reconstruction. However, 1 original trial and the
      meta-analysis found that there were no differences in the results between the 2
      types of reconstructions. Thus the utility of the anatomic double-bundle
      reconstruction has not yet been established. Our review does show how much
      evidence exists as to the benefits of double-bundle ACL reconstruction at
      present.

PMID- 20810092
TI  - Bone-to-bone fixation enhances functional healing of the porcine anterior
      cruciate ligament using a collagen-platelet composite.
AB  - PURPOSE: The purpose of this study was to determine whether providing bony
      stabilization between the tibia and femur improves the structural properties of
      an "enhanced" anterior cruciate ligament (ACL) repair using a collagen-platelet
      composite when compared with the traditional (Marshall) suture technique.
      METHODS: Twelve pigs underwent unilateral ACL transection and were treated with
      sutures connecting the bony femoral ACL attachment site to the distal ACL stump
      (ligament group) or to the tibia through a bone tunnel (tibia group). A collagen
      platelet composite was placed around the sutures to enhance the biological repair
      in both groups. Anteroposterior knee laxity and the graft structural properties
      were measured after 15 weeks of healing in both the ACL-repaired and
      contralateral, ACL-intact joints. RESULTS: Enhanced ACL repair with bone-to-bone
      fixation significantly improved yield load and linear stiffness of the ACL
      repairs (P < .05) after 15 weeks of healing. However, laxity values of the knees
      were similar in both groups of repaired knees (P > .10). CONCLUSIONS: Using an
      enhanced ACL suture repair technique that includes bone-to-bone fixation to
      protect the repair in the initial healing stages resulted in an ACL with improved
      structural properties after 15 weeks in the porcine model. CLINICAL RELEVANCE:
      The healing response of an ACL suture repair by use of a collagen-platelet
      composite can be enhanced by providing bony stabilization between the tibia and
      femur to protect the graft during the initial healing process in a translational
      model.

PMID- 20810093
TI  - Patellar tendon anterior cruciate ligament reconstruction in the high-demand
      patient: evaluation of autograft versus allograft reconstruction.
AB  - PURPOSE: This study sought to compare patient-reported and objective outcomes in
      high-demand patients after anterior cruciate ligament reconstruction with either
      patellar tendon allograft or autograft by use of a matched-pairs case-control
      experimental design. METHODS: Nineteen matched pairs were obtained based on
      gender (36.8% female patients), age (27.9 +/- 8.1 years in autograft group v 28.1
      +/- 9.1 years in allograft group), and length of follow-up (9.1 +/- 2.7 years in
      autograft group v 10.3 +/- 2.6 years in allograft group). All patients reported
      participating in very strenuous (soccer, basketball, and so on) or strenuous
      (skiing, tennis, and so on) sporting activity 4 to 7 times per week before their
      knee injury. Patient-reported outcomes included the International Knee
      Documentation Committee Subjective Knee Form, Activities of Daily Living and
      Sports Activity Scales of the Knee Outcome Survey, and Short Form 36. Clinical
      evaluation included knee range of motion, laxity, and functional strength.
      RESULTS: There were no statistically significant differences in gender, age, or
      body mass index. There was a slight difference in length of follow-up (P < .05).
      The groups showed no statistically significant differences in any of the patient
      reported or objective outcome measures. More autograft patients reported that
      they were able to perform very strenuous activity without the sense of
      instability (14 v 7), but this difference only approached statistical
      significance (P < .07). Twelve autograft patients were able to return to
      preinjury levels of sporting activity compared with ten allograft patients.
      Sixteen autograft patients and twelve allograft patients were able to participate
      in strenuous or very strenuous sporting activity at follow-up. Both differences
      were not statistically significant. CONCLUSIONS: Autograft and fresh-frozen
      allograft patellar tendon anterior cruciate ligament reconstruction exhibit
      similar patient-reported and objective outcomes in high-demand individuals at 3
      to 14 years' follow-up. LEVEL OF EVIDENCE: Level III, therapeutic case-control
      study.

PMID- 20810094
TI  - The value of tourniquet use for visibility during arthroscopy of the knee: a
      double-blind, randomized controlled trial.
AB  - PURPOSE: To study the value of tourniquet use during routine arthroscopy of the
      knee. METHODS: In this randomized, double-blind controlled trial, 245 patients
      were included from April 2005 until March 2007 and randomized into an inflated
      tourniquet group (n = 137) or a deflated tourniquet group (n = 108). The primary
      outcome was intraoperative visibility. Secondary outcomes were the need to
      intraoperatively inflate the tourniquet because impaired vision impeded the
      procedure, the number of times and reason (impaired vision or debris) for
      flushing the knee, the duration of the procedure (in minutes), and the surgeon's
      impression of whether the tourniquet was inflated during the procedure. RESULTS:
      Intraoperative visibility was statistically significantly better in the group
      with the inflated tourniquet. In 11 of the 16 cases in which visibility was rated
      fair/poor (unsatisfactory), the surgeon felt the need to inflate the tourniquet.
      In all of the cases the tourniquet had not been previously inflated. In all but 1
      case the visibility improved to at least to a rating of good. The frequency of
      flushing the knee intraoperatively was significantly higher in the deflated
      tourniquet group. The operative time was not significantly different
      statistically. CONCLUSIONS: The results of this study support our hypothesis that
      routine arthroscopy of the knee with an inflated tourniquet significantly
      improves visibility, but it does not shorten operative time. LEVEL OF EVIDENCE:
      Level I, therapeutic randomized controlled trial.

PMID- 20810096
TI  - From surfactant adsorption kinetics to asymmetric nanomembrane mechanics: pendant
      drop experiments with subphase exchange.
AB  - Adsorption equilibrium is the state in which the chemical potential of each
      species in the interface and bulk is the same. Dynamic phenomena at fluid-fluid
      interfaces in the presence of surface active species are often probed by
      perturbing an interface or adjoining bulk phase from the equilibrium state. Many
      methods designed for studying kinetics at fluid-fluid interfaces focus on
      removing the system from equilibrium through dilation or compression of the
      interface. This modifies the surface excess concentration Gamma(i) and allows the
      species distribution in the bulk C(i) to respond. There are only a few methods
      available for studying fluid-fluid interfaces which seek to control C(i) and
      allow the interface to respond with changes to Gamma(i). Subphase exchange in
      pendant drops can be achieved by the injection and withdrawal of liquid into a
      drop at constant volumetric flow rate R(E) during which the interfacial area and
      drop volume V(D) are controlled to be approximately constant. This can be
      accomplished by forming a pendant drop at the tip of two coaxial capillary tubes.
      Although evolution of the subphase concentration C(i)(t) is dictated by extrinsic
      factors such as R(E) and V(D), complete subphase exchange can always be attained
      when a sufficient amount of liquid is used. This provides a means to tailor
      driving forces for adsorption and desorption in fluid-fluid systems and in some
      cases, fabricate interfacial materials of well-defined composition templated at
      these interfaces. The coaxial capillary pendant drop (CCPD) method opens a wide
      variety of experimental possibilities. Experiments and theoretical frameworks are
      reviewed for the study of surfactant exchange kinetics, macromolecular adsorption
      equilibrium and dynamics, as well as the fabrication of a wide range of soft
      surface materials and the characterization of their mechanics. Future directions
      for new experiments are also discussed.

PMID- 20810095
TI  - Four-year results from a randomized controlled study of knee chondroplasty with
      concomitant medial meniscectomy: mechanical debridement versus radiofrequency
      chondroplasty.
AB  - PURPOSE: This randomized study was undertaken to compare the effectiveness of
      simple mechanical debridement and 50 degrees C controlled bipolar chondroplasty.
      METHODS: A total of 60 patients who had a grade III articular cartilage defect of
      the medial femoral condyle were included. After randomization, 30 patients
      underwent simple debridement of articular cartilage defects, which was performed
      with a mechanical shaver (mechanical shaver debridement [MSD] group). The
      remaining patients underwent thermal chondroplasty, which was performed with a
      temperature-controlled bipolar device with a constant thermo-application of a
      maximum of 50 degrees C (radiofrequency-based chondroplasty [RFC] group). All
      patients underwent partial (n = 41) or subtotal (n = 19) meniscectomy. Follow-up
      was undertaken 4 years postoperatively. RESULTS: No significant differences
      between the preoperative findings for the 2 groups were observed. One patient
      from the MSD group had died, and one female patient in the RFC group was lost to
      follow-up. A total of 18 patients had undergone revision operations for
      persistent knee problems: in the MSD group, there were 8 endoprostheses, 4
      osteotomies, and 2 revision arthroscopies, whereas in the RFC group, there was 1
      replacement, 2 osteotomies, and 1 revision arthroscopy with subtotal medial
      meniscectomy. The proportion of revisions was significantly higher in the MSD
      group (P = .006). These patients were excluded from the evaluation. The remaining
      40 patients from both groups benefited from the operation. The preoperative Knee
      Injury and Osteoarthritis Outcome Score (KOOS) was 11.3 points in the MSD group
      and 15.5 points in the RFC group (P = .279). Patients from the MSD group had a
      KOOS of 53.2 points at the time of follow-up. In the RFC group the KOOS (71.8
      points) was significantly higher (P < .001). CONCLUSIONS: Compared with classical
      mechanical debridement, bipolar radiofrequency currently appears to be the
      superior method for achieving a good midterm result. LEVEL OF EVIDENCE: Level I,
      randomized controlled trial.

PMID- 20810097
TI  - Concentration polarization of interface and non-linear electrokinetic phenomena.
AB  - The review addresses the peculiarities of concentration polarization caused by an
      electric current passing through conducting and around nonconducting charged
      materials. The conditions of emergence of an induced space charge of large
      density and thickness behind an electrical double layer, leading to strong non
      linearity of electroosmosis and electrophoresis, are analyzed. Basic findings
      about concentration polarization, its theoretical modeling and experimental
      investigations, as well as its influence on electrokinetic phenomena and mass
      transfer through ion-exchange materials are discussed from the point of view of
      the fundamental knowledge about polarization processes and from the perspective
      of their practical application. The analysis focuses on the main properties of
      concentration polarization, electroosmotic flow of liquid around single fixed
      particles and through the system of particles, and electrophoresis of particles
      suspended in aqueous medium and current through flat, spherical and cylindrical
      interfaces and membranes with heterogeneous conductivity. The paper also presents
      the general ideas of concentration polarization and non-linear electrokinetic
      phenomena in case of nonconducting particles and their dependence on particle
      surface electroconductivity. Existing theoretical models describing polarization
      of nonconducting particles at high and low Peclet numbers are analyzed, with
      appropriate experimental data being provided to validate the theory. A joint
      analysis of polarization of conducting and nonconducting particles completes the
      review.

PMID- 20810098
TI  - Intramuscular 17alpha-hydroxyprogesterone caproate administration attenuates
      immunoresponsiveness of maternal peripheral blood mononuclear cells.
AB  - OBJECTIVE: 17alpha-hydroxyprogesterone caproate (17P) may decrease risk of
      prematurity by suppressing maternal immunity. We hypothesized that in vivo 17P
      treatment attenuates immunoresponsiveness of peripheral blood mononuclear cells
      (PBMCs). STUDY DESIGN: Study subjects were gravidas receiving weekly prophylactic
      intramuscular 17P injections. Peripheral blood samples were obtained at 21-27
      weeks' gestation. Gestational age-matched, drug-naive gravidas served as
      controls. To simulate infection, isolated PBMCs were stimulated with lipoteichoic
      acid (LTA) or lipopolysaccharide (LPS). Extracellular interleukin-6 (IL-6)
      concentrations were quantified by an enzyme-linked immunosorbent assay. RESULTS:
      Unstimulated IL-6 levels were comparable in PBMCs derived from drug-naive and 17P
      treated subjects. LPS and LTA induced a dose-dependent elevation of IL-6 in
      control PBMCs. In patients who received exogenous 17P, LPS, and LTA stimulated
      induction of IL-6 was significantly decreased compared with controls (P = .005
      and P = .02). CONCLUSION: In vivo 17P attenuated immunoreactivity of PBMCs in our
      in vitro model of Gram-positive and Gram-negative bacterial infection.

PMID- 20810099
TI  - Two-component polyethylene glycol surgical sealant influence on intraperitoneal
      infection in a refined rodent model.
AB  - OBJECTIVE: This study determined the influence of a 2-component polyethylene
      glycol surgical sealant (Coseal) as an adhesion prevention device on sepsis
      related mortality and/or systemic bacterial translocation to the spleen. STUDY
      DESIGN: A bacterial inoculum and telemetry probe were implanted in 50 treated and
      49 untreated rats. Telemetry probes monitored core-body temperature to determine
      time of death. Spleens were collected on day 3 for quantitative bacteriology of
      Escherichia coli and Bacteroides fragilis. RESULTS: Median survival time and
      mortality of treated rats (37.0 hours, 54.0%) were noninferior to untreated rats
      (47.5 hours, 55.1%). Median E coli titers in treated rats (2.24 log colony
      forming units/spleen) were significantly less than untreated rats (4.32 log
      colony forming units/spleen). B fragilis titers were not different. CONCLUSION:
      This study demonstrates intraperitoneal administration of a 2-component
      polyethylene glycol surgical sealant as an adhesion prevention device does not
      alter time to death or sepsis-related mortality and/or systemic bacterial
      translocation to the spleen.

PMID- 20810100
TI  - Interpretation bias and depressive symptoms: The role of self-relevance.
AB  - Cognitive theories of depression emphasize negatively biased interpretations as
      an important target of therapy. Much of the research on interpretation bias in
      depression has focused on selection, or deciding which of several interpretations
      is likely. However, depressive biases may also exist in the generation of
      possible interpretations, or the ability to think of positive alternatives. If
      biases exist for generation as well as selection, therapeutic techniques to
      encourage the generation of more positive interpretations would be warranted.
      Asking therapy clients to consider someone else in a similar situation is a
      commonly used therapy strategy but has not been sufficiently examined
      empirically. In the current studies, we examine interpretation generation and
      selection in dysphoric and nondysphoric individuals, and contrast interpretations
      made for the self to interpretations made for two types of "other." Our studies
      reveal depressive biases in both interpretation generation and selection, and
      indicate that interpretation valence is highly sensitive to the type of other
      considered. All participants generated and selected significantly more positive
      interpretations for friends than for themselves, but generated significantly more
      negative interpretations for hypothetical others than for themselves. Our results
      suggest that encouraging dysphoric individuals to imagine others can be
      beneficial, but the type of "other" used is critically important, with
      instructions to consider a close friend most likely to be effective in decreasing
      negativity in interpretation.

PMID- 20810102
TI  - Synthesis of a core disaccharide from the Streptococcus pneumoniae type 23F
      capsular polysaccharide antigen.
AB  - The synthesis of methyl alpha-l-rhamnopyranosyl-(1->2)-beta-d-galactopyranoside
      and methyl alpha-l-rhamnopyranosyl-(1->2)-3-(glycer-2-yl-phosphate)-beta-d
      galactopyranoside disaccharides from the Streptococcuspneumoniae type 23F
      capsular polysaccharide is reported. A simple protecting group strategy was
      followed using commercially available monosaccharides and phosphorylating
      reagents. H-Phosphonate and phosphoramidite coupling chemistries were explored
      for introducing the phosphodiester. Hydrazine hydrate was found to be a mild and
      efficient deacetylating agent, which was required to avoid phosphate migration
      during the deprotection of the phosphodiester functionalized disaccharide.

PMID- 20810101
TI  - How does mindfulness-based cognitive therapy work?
AB  - Mindfulness-based cognitive therapy (MBCT) is an efficacious psychosocial
      intervention for recurrent depression (Kuyken et al., 2008; Ma & Teasdale, 2004;
      Teasdale et al., 2000). To date, no compelling research addresses MBCT's
      mechanisms of change. This study determines whether MBCT's treatment effects are
      mediated by enhancement of mindfulness and self-compassion across treatment,
      and/or by alterations in post-treatment cognitive reactivity. The study was
      embedded in a randomized controlled trial comparing MBCT with maintenance
      antidepressants (mADM) with 15-month follow-up (Kuyken et al., 2008). Mindfulness
      and self-compassion were assessed before and after MBCT treatment (or at
      equivalent time points in the mADM group). Post-treatment reactivity was assessed
      one month after the MBCT group sessions or at the equivalent time point in the
      mADM group. One hundred and twenty-three patients with >=3 prior depressive
      episodes, and successfully treated with antidepressants, were randomized either
      to mADM or MBCT. The MBCT arm involved participation in MBCT, a group-based
      psychosocial intervention that teaches mindfulness skills, and discontinuation of
      ADM. The mADM arm involved maintenance on a therapeutic ADM dose for the duration
      of follow-up. Interviewer-administered outcome measures assessed depressive
      symptoms and relapse/recurrence across 15-month follow-up. Mindfulness and self
      compassion were measured using self-report questionnaire. Cognitive reactivity
      was operationalized as change in depressive thinking during a laboratory mood
      induction. MBCT's effects were mediated by enhancement of mindfulness and self
      compassion across treatment. MBCT also changed the nature of the relationship
      between post-treatment cognitive reactivity and outcome. Greater reactivity
      predicted worse outcome for mADM participants but this relationship was not
      evident in the MBCT group. MBCT's treatment effects are mediated by augmented
      self-compassion and mindfulness, along with a decoupling of the relationship
      between reactivity of depressive thinking and poor outcome. This decoupling is
      associated with the cultivation of self-compassion across treatment.

PMID- 20810103
TI  - Mathematical model of the coagulation in the bone-dental implant interface.
AB  - The healing of the injured tissues after the insertion of a dental implant begins
      with the formation of a fibrin clot that detains the blood flow and gives initial
      support to the osteoprogenitor cells. The adequate formation of this clot
      determines the direct and stable connection between bone and implant, process
      known as osseointegration. The aim of this work is to introduce a mathematical
      model of the coagulation in the bone-dental implant interface based on two
      reaction-diffusion equations representing the kinetic reaction that leads to the
      production of fibrin and a transformation equation representing the formation of
      the fibrillar network compounding the clot. The model also includes a parameter
      associated to the blood platelets concentration that extends the model framework
      to the analysis of two hematological disorders well reported: thrombocytosis and
      thrombocytopenia. The solution of the model is performed using the finite element
      method, obtaining as results the distribution of spatial-temporal patterns in the
      bone-dental implant interface. These results are in qualitative concordance with
      experimental results previously reported by other authors. Although the model is
      a simplified version of the biological process of coagulation, the results here
      obtained justify the mathematical formulation implemented. It is concluded that
      the model can be used as a methodological basis for the formulation of a general
      model of the osseointegration in the bone-dental implant interface.

PMID- 20810104
TI  - Electroencephalogram signals processing for topographic brain mapping and
      epilepsies classification.
AB  - In this study, topographic brain mapping and wavelet transform-neural network
      method are used for the classification of grand mal (clonic stage) and petit mal
      (absence) epilepsies into healthy, ictal and interictal (EEGs). Preprocessing is
      included to remove artifacts occurred by blinking, wandering baseline (electrodes
      movement) and eyeball movement using the Discrete Wavelet Transformation (DWT).
      De-noising EEG signals from the AC power supply frequency with a suitable notch
      filter is another job of preprocessing. In experimental data, the preprocessing
      enhanced speed and accuracy of the processing stage (wavelet transform and neural
      network). The EEGs signals are categorized to normal and petit mal and clonic
      epilepsy by an expert neurologist. The categorization is confirmed by Fast
      Fourier Transform (FFT) analysis and brain mapping. The dataset includes waves
      such as sharp, spike and spike-slow wave. Through the Counties Wavelet Transform
      (CWT) of EEG records, transient features are accurately captured and separated
      and used as classifier input. We introduce a two-stage classifier based on the
      Learning Vector Quantization (LVQ) neural network location in both time and
      frequency contexts. The brain mapping used for finding the epilepsy locates in
      the brain. The simulation results are very promising and the accuracy of the
      proposed classifier in experimental clinical data is ~80%.

PMID- 20810105
TI  - The effect of air bubble position after blastocyst transfer on pregnancy rates in
      IVF cycles.
AB  - OBJECTIVE: To investigate the relationship between air bubble position after
      blastocyst transfer (BT) and pregnancy rates (PRs). DESIGN: Retrospective cohort
      study. SETTING: University-based infertility center. PATIENT(S): Three hundred
      fifteen consecutive nondonor BTs by a single provider. INTERVENTION(S): Catheters
      were loaded with 25 MUL of culture media, 20 MUL of air, 25 MUL of media
      containing the blastocysts, 20 MUL of air, and a small amount of additional
      media. The distance from the air bubble to the fundus, as seen on abdominal
      ultrasound examination, was measured at the time of transfer. Air bubble location
      was categorized as <10 mm, 10-20 mm, and >20 mm from the fundus. MAIN OUTCOME
      MEASURE(S): Clinical pregnancy rate. RESULT(S): After controlling for age,
      parity, FSH and frozen transfers, and accounting for repeated cycles per patient,
      the PRs for both the >20-mm (38.3%) and the 10-20-mm (42.0%) from the fundus
      group were significantly reduced compared with the group in which the bubble was
      <10 mm from the fundus (62.5%). CONCLUSION(S): This study is the first to suggest
      that BT closer to the fundus is associated with higher PR. Although no ectopic
      pregnancies occurred in the <10-mm group, this outcome should be monitored
      closely in larger studies.

PMID- 20810106
TI  - Biological predictive criteria for clinical pregnancy after elective single
      embryo transfer.
AB  - In this prospective observational study, the onset of a clinical pregnancy after
      elective single embryo transfer (eSET) was significantly associated with: 1) the
      woman's age as well as the number of good- and top-quality embryos; and 2) the
      day of the embryo transfer (day 3>day 2). Good-quality embryos had the same
      ability to implant, regardless of the zygotic score, the day 1 early cleavage
      rate, the fragmentation degree, and the top-quality assessment, specifying the
      eligibility criteria for eSET.

PMID- 20810107
TI  - Cetrorelix lowers premature luteinization rate in gonadotropin ovulation
      induction-intrauterine insemination cycles: a randomized-controlled clinical
      trial.
AB  - Attempting to compare the rates of premature luteinization (PL), clinical
      pregnancy, and cycle cancellation in ovulation induction-intrauterine
      insemination (OI-IUI) cycles with and without the GnRH antagonist, cetrorelix, a
      randomized-controlled trial was undertaken in which patients were randomized to
      one of two OI-IUI protocols. Those in the cetrorelix arm showed a significantly
      reduced rate of PL and no change in clinical pregnancy or cycle cancellation
      rate, leading to the conclusion that GnRH antagonists can decrease the rate of
      PL, but appear to have no effect on pregnancy or cycle cancellation in
      gonadotropin OI-IUI cycles.

PMID- 20810108
TI  - National maternal mortality ratio for Jordan, 2007-2008.
AB  - OBJECTIVE: To estimate the number of maternal deaths per 100000 live births
      during 2007-2008 among Jordanian women; to identify the causes of maternal
      mortality; and to compare the results with those of the last report for 1995
      1996. METHODS: Reproductive-age mortality study of maternal deaths among women
      aged 15-49 years in Jordan in 2007-2008. RESULTS: Among 1406 identified deaths of
      reproductive-aged women, 76 maternal deaths were identified out of 397588 live
      births, for a maternal mortality ratio of 19.1 deaths per 100000 live births.
      Forty-three (56.6%) deaths were attributable to hemorrhage, thrombosis and
      thromboembolism, and sepsis. Avoidable factors were present in 53.9% of women,
      52.6% had substandard care, and 31.5% had 3 or fewer antenatal visits. Of those
      with available information on family planning, only 29.4% had ever used any form
      of contraception. CONCLUSIONS: Maternal deaths in Jordan are declining. The
      maternal mortality ratio of 19.1 deaths per 100000 live births reported for 2007
      2008 showed a remarkable reduction of 53.9% achieved in the 12 years since the
      1995-1996 report (a 4.5% annual reduction), which is approaching the 75%
      reduction recommended by Millennium Development Goal 5.

PMID- 20810109
TI  - Effect of atorvastatin on kidney function in chronic kidney disease: a randomised
      double-blind placebo-controlled trial.
AB  - BACKGROUND: The effect of atorvastatin on kidney function was assessed in
      patients with stages 2-4 chronic kidney disease. METHODS: We conducted a
      randomised, double-blind, placebo-controlled trial in chronic kidney disease
      clinics in Northern Tasmania and enrolled 132 patients with serum creatinine
      levels >120 MUmol/l, not taking lipid-lowering therapy and at all levels of
      proteinuria and serum cholesterol. Patients were randomly assigned to receive
      either 10 mg of atorvastatin/day (64) or placebo (68) and were followed with
      trial visits 3-monthly for a mean of 2.5 yrs. The primary outcome was the rate of
      both MDRD eGFR and Cockcroft-Gault creatinine clearance (C-G CrCl) decline.
      Analysis was based on intention to treat and included all patients that had at
      least one follow-up visit. RESULTS: The rate of MDRD eGFR decline was 29% lower;
      1.04 +/- 3.84 vs. 1.47 +/- 3.74 ml/min/1.73 m(2)/yr (P=0.53), and the C-G CrCl
      was 20% lower; 1.88 +/- 5.07 vs. 2.36 +/- 4.61 ml/min/1.73 m(2)/yr (P=0.58) in
      atorvastatin-treated, compared with placebo-treated patients. Although blood
      pressure decreased in both atorvastatin and placebo-treated groups there were no
      differences between groups. In addition, there was no difference in concomitant
      medication intake including angiotensin converting enzyme inhibitors and
      angiotensin receptor blockers between groups. CONCLUSIONS: There was a trend
      toward a slower eGFR decline in the atorvastatin-treated group that did not reach
      statistical significance. This may have been due to the lack of power of the
      study. However, atorvastatin may have a renoprotective effect in those patients
      with chronic kidney disease and cardiovascular disease. This needs to be assessed
      in further studies.

PMID- 20810110
TI  - Role of transglutaminases in cuff-induced atherosclerotic lesion formation in
      femoral arteries of ApoE3 Leiden mice.
AB  - Transglutaminases play an important role in vascular remodeling, calcification,
      cell adhesion and endothelial barrier function. In this study we investigate the
      influence of combined inhibition of both tissue-type transglutaminase (TG2) and
      the plasma transglutaminase FXIIIA on early lesion development. METHODS: A cuff
      was placed around the femoral arteries of ApoE3 Leiden mice while fed a Western
      type diet to induce atherosclerotic lesion development. An osmotic minipump was
      placed in the intraperitoneal cavity containing an irreversible inhibitor of TG2
      and FXIIIA activity ((1,3,4,5-tetramethyl-2-[(2-oxopropyl)thio]imidazolium
      chloride, Zedira). Atherosclerotic lesion composition was analyzed using
      immunohistochemistry and RT-PCR. RESULTS: Inhibition of transglutaminases did not
      influence lesion size or geometric remodeling of the vessels. However, systemic
      transglutaminase inhibition resulted in 41% less macrophage infiltrate in the
      media of the vessels. Additional in vitro experiments on HL60 cells confirmed a
      decreased migratory response during transglutaminase inhibition. CONCLUSION:
      Inhibition of TG2 and FXIIIA during early development of lesions reduced the
      macrophage content in the media of atherosclerotic vessels, while not affecting
      lesion size or geometric remodeling.

PMID- 20810111
TI  - Immune responses against aldehyde-modified laminin accelerate atherosclerosis in
      Apoe-/- mice.
AB  - BACKGROUND: LDL oxidation in the vascular wall is associated with aldehyde
      modification of surrounding extracellular matrix proteins that may target
      autoimmune responses against vascular tissues. Here we investigated the possible
      influence of immunity against a malondialdehyde (MDA)-modified form of the
      basement membrane protein laminin on atherosclerosis. METHODS AND RESULTS: IgM
      and IgG autoantibodies were present in human plasma and a prospective clinical
      study demonstrated that individuals who later suffered from acute cardiovascular
      events had lower levels of MDA-laminin antibodies compared to those in the
      control group. Immunohistochemical analysis of atherosclerotic plaques from Apoe
      /- mice demonstrated co-localization between laminin and MDA epitopes, however
      MDA-laminin IgG was absent in mouse plasma. To determine the effect of MDA
      laminin immunity, Apoe-/- mice were immunized with MDA-laminin. Analysis of
      circulating leukocytes at 12 weeks demonstrated increased T-cell activation,
      expansion of Th17 cells and a lower fraction of regulatory T cells (Tregs) in
      mice immunized with MDA-laminin. At 25 weeks, aortic atherosclerosis was
      increased by more than 60% in mice immunized with MDA-laminin, together with
      increased levels of MDA-laminin IgG1 and MDA-laminin-specific T-cells expressing
      IL-2, IL-4 and IL-6 in the spleen. CONCLUSION: The clinical observations suggest
      that immune responses against MDA-laminin may be involved in the development of
      cardiovascular disease in humans. Furthermore, observations in mice provide
      evidence for the presence of aldehyde-modified laminin in atherosclerotic lesions
      and demonstrate that induction of an immune response against these structures is
      associated with activation of Th17 cells, reduced fraction of Tregs and a more
      aggressive development of atherosclerosis.

PMID- 20810112
TI  - Bone marrow mononuclear cells reduce myocardial reperfusion injury by activating
      the PI3K/Akt survival pathway.
AB  - OBJECTIVE: Adult bone marrow mononuclear cells (BMMNCs) can restore cardiac
      function following myocardial necrosis. Protocols used to date have administered
      cells relatively late after ischaemia/reperfusion injury, but there is the
      opportunity with elective procedures to infuse cells shortly after restoration of
      blood flow, for example after angioplasty. Our aim was therefore to try and
      quantify protection from myocardial injury by early infusion of BMMNCs in a rat
      ischaemia reperfusion (I/R) model. METHODS AND RESULTS: Male Wistar rats
      underwent 25 min of ischaemia followed by 2 h reperfusion of the left anterior
      descending coronary artery. Ten million BMMNCs were injected i.v. at reperfusion.
      We found BMMNCs caused a significant reduction in infarct size at 2 h when
      assessed by staining the area at risk with p-nitro blue tetrazolium (42%
      reduction, P<0.01). Apoptosis and necrosis of isolated cardiomyocytes was
      significantly reduced in the area at risk. Functional assessment at 7 days using
      echocardiography and left ventricular catheterisation showed improved systolic
      and diastolic function in the BMMNC treatment group (LVEF: BMMNC 71 +/- 3% vs.
      PBS 48 +/- 4%, P<0.0001). In functional studies BMMNC injected animals showed
      increased activation of Akt, inhibition of GSK-3beta, amelioration of p38 MAP
      kinase phosphorylation and NF-kappaB activity compared to control myocardium.
      Inhibition of PI3K with LY294002 abolished all beneficial effects of BMMNC
      treatment. Proteomic analysis also demonstrated that BMMNC treatment induced
      alterations in proteins within known cardioprotective pathways, e.g., heat shock
      proteins, stress-70 protein as well as the chaperone protein 14-3-3 epsilon.
      CONCLUSIONS: Early BMMNC injection during reperfusion preserves the myocardium,
      with evidence of reduced apoptosis, necrosis, and activation of survival
      pathways.

PMID- 20810113
TI  - In vivo knockdown of nicotinic acetylcholine receptor alpha1 diminishes aortic
      atherosclerosis.
AB  - OBJECTIVE: Nicotinic acetylcholine receptor alpha1 (nAChRalpha1) was recently
      identified as a functional cell receptor for urokinase, a potent atherogenic
      molecule. Here, we test the hypothesis that nAChRalpha1 plays a role in the
      pathogenesis of atherosclerosis. METHODS: Apolipoprotein E-deficient mice were
      initially fed a Western diet for 8 wks. Plasmid DNA encoding scramble RNA (pscr)
      or siRNA (psir2) for nAChRalpha1 was injected into the mice (n=16) using an
      aortic hydrodynamic gene transfer protocol. Four mice from each group were
      sacrificed 7 days after the DNA injection to confirm the nAChRalpha1 gene
      silencing. The remaining mice continued on a Western diet for an additional 16
      wks. RESULTS: The nAChRalpha1 was up-regulated in aortic atherosclerotic lesions.
      A 78% knockdown of the nAChRalpha1 gene resulted in remarkably less severe aortic
      plaque growth and neovascularization at 16 wks (both P<0.05). In addition,
      significantly fewer macrophages (60% less) and myofibroblasts (80% less)
      presented in the atherosclerotic lesion of the psir2-treated mice. The protective
      mechanisms of the nAChRalpha1 knockdown may involve up-regulating interferon
      gamma/Y box protein-1 activity and down-regulating transforming growth factor
      beta expression. CONCLUSIONS: The nAChRalpha1 gene plays a significant role at
      the artery wall, and reducing its expression decreases aortic plaque development.

PMID- 20810115
TI  - Objective grading of the pivot shift phenomenon using a support vector machine
      approach.
AB  - The pivot shift test is the only clinical test that has been shown to correlate
      with subjective criteria of knee joint function following rupture of the anterior
      cruciate ligament. The grade of the pivot shift is important in predicting short-
      and long-term outcome. However, because this grade is established by a clinician
      in a subjective manner, the pivot shift's value as a clinical tool is reduced.
      The purpose of this study was to develop a system that will objectively grade the
      pivot shift test based on recorded knee joint kinematics. Fifty-six subjects with
      different degrees of knee joint stability had the pivot shift test performed by
      one of eight different orthopaedic surgeons while their knee joint kinematics
      were recorded. A support vector machine based algorithm was used to objectively
      classify these recordings according to a clinical grade. The grades established
      by the surgeons were used as the gold standard for the development of the
      classifier. There was substantial agreement between our classifier and the
      surgeons in establishing the grade (weighted kappa=0.68). Seventy-one of 107
      recordings (66%) were given the same grade and 96% of the time our classifier was
      within one grade of that given by the surgeons. Moreover, grades 0 and 1 were
      distinguished from grade 2 to 3 with 86% sensitivity and 90% specificity. Our
      results show the feasibility of automatically grading the pivot shift in a manner
      similar to that of an experienced clinician, based on knee joint kinematics.

PMID- 20810114
TI  - The effect of connective tissue material uncertainties on knee joint mechanics
      under isolated loading conditions.
AB  - Although variability in connective tissue parameters is widely reported and
      recognized, systematic examination of the effect of such parametric uncertainties
      on predictions derived from a full anatomical joint model is lacking. As such, a
      sensitivity analysis was performed to consider the behavior of a three
      dimensional, non-linear, finite element knee model with connective tissue
      material parameters that varied within a given interval. The model included the
      coupled mechanics of the tibio-femoral and patello-femoral degrees of freedom.
      Seven primary connective tissues modeled as non-linear continua, articular
      cartilages described by a linear elastic model, and menisci modeled as transverse
      isotropic elastic materials were included. In this study, a multi-factorial
      global sensitivity analysis is proposed, which can detect the contribution of
      influential material parameters while maintaining the potential effect of
      parametric interactions. To illustrate the effect of material uncertainties on
      model predictions, exemplar loading conditions reported in a number of isolated
      experimental paradigms were used. Our findings illustrated that the inclusion of
      material uncertainties in a coupled tibio-femoral and patello-femoral model
      reveals biomechanical interactions that otherwise would remain unknown. For
      example, our analysis revealed that the effect of anterior cruciate ligament
      parameter variations on the patello-femoral kinematic and kinetic response
      sensitivities was significantly larger, over a range of flexion angles, when
      compared to variations associated with material parameters of tissues intrinsic
      to the patello-femoral joint. We argue that the systematic sensitivity framework
      presented herein will help identify key material uncertainties that merit further
      research and provide insight on those uncertainties that may not be as relative
      to a given response.

PMID- 20810116
TI  - Simple capillary flow porometer for characterization of capillary columns
      containing packed and monolithic beds.
AB  - A simple capillary flow porometer (CFP) was assembled for through-pore structure
      characterization of monolithic capillary liquid chromatography columns in their
      original chromatographic forms. Determination of differential pressures and flow
      rates through dry and wet short capillary segments provided necessary information
      to determine the mean diameters and size distributions of the through-pores. The
      mean through-pore diameters of three capillary columns packed with 3, 5, and 7
      MUm spherical silica particles were determined to be 0.5, 1.0 and 1.4 MUm, with
      distributions ranging from 0.1 to 0.7, 0.3 to 1.1 and 0.4 to 2.6 MUm,
      respectively. Similarly, the mean through-pore diameters and size distributions
      of silica monoliths fabricated via phase separation by polymerization of
      tetramethoxysilane (TMOS) in the presence of poly(ethylene glycol) (PEG) verified
      that a greater number of through-pores with small diameters were prepared in
      columns with higher PEG content in the prepolymer mixture. The CFP system was
      also used to study the effects of column inner diameter and length on through
      pore properties of polymeric monolithic columns. Typical monoliths based on butyl
      methacrylate (BMA) and poly(ethylene glycol) diacrylate (PEGDA) in capillary
      columns with different inner diameters (i.e., 50-250 MUm) and lengths (i.e., 1.5
      3.0 cm) were characterized. The results indicate that varying the inner diameter
      and/or the length of the column had little effect on the through-pore properties.
      Therefore, the through-pores are highly interconnected and their determination by
      CFP is independent of capillary length.

PMID- 20810117
TI  - Determination of non-steroidal anti-inflammatory drugs in sewage sludge by direct
      hollow fiber supported liquid membrane extraction and liquid chromatography-mass
      spectrometry.
AB  - In this study, a three-phase hollow fiber liquid-phase microextraction (HF-LPME)
      method combined with liquid chromatography-mass spectrometry was developed for
      direct determination of four non-steroidal anti-inflammatory drugs (ketoprofen,
      naproxen, diclofenac and ibuprofen) in sewage sludge. The drugs were extracted
      from non-spiked and spiked slurry samples with different amounts of sludge into
      an organic phase and then back-extracted into an aqueous phase held in the lumen
      of the hollow fiber. High enrichment factors ranging from 2761 to 3254 in pure
      water were achieved. In sludge samples, repeatability and inter-day precision
      were tested with relative standard deviation values between 10-18% and 7-15%,
      respectively. Average concentrations of 29+/-9, 138+/-2, 39+/-5 and 122+/-7 ng/g
      were determined in dried sludge from Kallby sewage treatment plant (Sweden) for
      ketoprofen, naproxen, diclofenac and ibuprofen, respectively.

PMID- 20810118
TI  - Multiresidue analysis of sulfonamides in meat by supramolecular solvent
      microextraction, liquid chromatography and fluorescence detection and method
      validation according to the 2002/657/EC decision.
AB  - A multiresidue method was described for determining eight sulfonamides, SAs
      (sulfadiazine, sulfamerazine, sulfamethoxypyridazine, sulfachloropyridazine,
      sulfadoxine, sulfamethoxazole, sulfadimethoxine and sulfaquinoxaline) in animal
      muscle tissues (pork, chicken, turkey, lamb and beef) at concentrations below the
      maximum residue limit (100 MUg kg(-1)) set by the European Commission. The method
      was based on the microextraction of SAs in 300-mg muscle samples with 1 mL of a
      supramolecular solvent made up of reverse micelles of decanoic acid (DeA) and
      posterior determination of SAs in the extract by LC/fluorescence detection, after
      in situ derivatization with fluorescamine. Recoveries were quantitative (98-109%)
      and matrix-independent, no concentration of the extracts was required, the
      microextraction took about 30 min and several samples could be simultaneously
      treated. Formation of multiple hydrogen bonds between the carboxylic groups of
      the solvent and the target SAs (hydrogen donor and acceptor sum between 9 and 11)
      were considered as the major forces driving microextraction. The method was
      validated according to the European Union regulation 2002/657/EC. Analytical
      performance in terms of linearity, selectivity, trueness, precision, stability of
      SAs, decision limit and detection capability were determined. Quantitation limits
      for the different SAs ranged between 12 MUg kg(-1) and 44 MUg kg(-1), they being
      nearly independent of matrix composition. Repeatability and reproducibility,
      expressed as relative standard deviation, were in the ranges 1.8-3.6% and 3.3
      6.1%. The results of the validation process proved that the method is suitable
      for determining sulfonamide residues in surveillance programs.

PMID- 20810119
TI  - On-line sample concentration of organic anions in capillary zone electrophoresis
      by micelle to solvent stacking.
AB  - Micelle to solvent stacking (MSS) is a new on-line sample concentration technique
      for charged analytes in capillary zone electrophoresis (CZE). Sample
      concentration in MSS mainly relies on the reversal in the effective
      electrophoretic mobility of the analyte at the boundary zone between the sample
      solution (S) and CZE background solution (BGS) inside the capillary. The basic
      condition for MSS is that the S is prepared in a matrix that contains an additive
      (i.e., micelles) which interacts with and has an opposite charge compared to the
      analytes. In addition, the BGS must contain a sufficient percentage of organic
      solvent. MSS was first reported for organic cations using anionic dodecyl sulfate
      micelles as additive in the S and methanol or acetonitrile as organic solvent in
      the BGS. Here, theoretical and experimental studies on MSS are described for
      organic anions using cationic cetyltrimethyl ammonium micelles as additive in the
      S and methanol as organic solvent in the BGS. Up to an order of magnitude
      improvement in concentration sensitivity was obtained for the test hypolipidaemic
      drugs using MSS in CZE with UV detection. The optimized method was also evaluated
      to the analysis of a spiked wastewater sample that was subjected to a simple
      extraction step.

PMID- 20810120
TI  - Development of a multi-class method for the quantification of veterinary drug
      residues in feedingstuffs by liquid chromatography-tandem mass spectrometry.
AB  - A simple multi-residue method was developed for detecting and quantifying 33
      analytes from 13 classes of antibiotics (tetracyclines (3), quinolones (7),
      penicillins (3), ionophore coccidiostats (7), macrolides (3), sulfonamides (1),
      quinoxalines (2), phenicols (2), lincosamides (1), diaminopyrimidines (1),
      polypeptides (1), streptogramins (1) and pleuromutilins (1)) in animal feeds.
      Extraction and clean-up procedures were optimized with spiked piglet feed.
      Samples were extracted by ultrasonic-assisted extraction with a mixture of
      methanol/acetonitrile/McIlvaine buffer at pH 4.6 (37.5/37.5/25, v/v/v) containing
      0.3% of EDTA-Na(2), followed by a clean up using a dispersive solid-phase
      extraction (d-SPE) with PSA (primary secondary amine). Detection of antibiotics
      was achieved by liquid chromatography-electrospray tandem mass spectrometry (LC
      ESI-MS/MS) within 28 min using both positive and negative ESI mode. Average
      recoveries ranged from 51% (oxytetracycline) to 116% (tilmicosin) with associated
      relative standard deviations of 7.3% and 9.0% and an overall mean of 87%. Limits
      of quantification ranged from 3.8 ngg(-1) (lincomycin) to 65.0 ngg(-1)
      (bacitracin). Following optimization, the method was further verified for bovine
      and lamb feeding stuffs; negative matrix effects were evaluated and overcome by a
      standard addition method.

PMID- 20810121
TI  - Simultaneous determination of polysorbate 20 and unbound polyethylene-glycol in
      protein solutions using new core-shell reversed phase column and condensation
      nucleation light scattering detection.
AB  - A novel fast and sensitive method has been developed for the specific
      simultaneous determination of polysorbate 20 (Tween 20) and unbound polyethylene
      glycol (PEG) from liquid formulations in the presence of proteins and excipients.
      The quantitative determination is based on a fast liquid chromatographic (HPLC)
      separation and condensation nucleation light scattering detection (CNLSD or
      NQADTM). The method uses a Kinetex core-shell column (100 mm * 3 mm, 2.6 MUm) and
      methanol-water-trifluoroacetic acid mobile phase. The rapid HPLC-CNLSD method
      presented here is suitable for quantifying polysorbate 20 in the range of 10-60
      MUg/ml and unbound PEG in the range of 2-40 MUg/ml in protein solutions within
      good manufacturing practices (GMP) of the pharmaceutical industry.

PMID- 20810122
TI  - Protein- versus peptide fractionation in the first dimension of two-dimensional
      high-performance liquid chromatography-matrix-assisted laser
      desorption/ionization tandem mass spectrometry for qualitative proteome analysis
      of tissue samples.
AB  - The availability of robust and highly efficient separation methods represents a
      major requirement for proteome analysis. This study investigated the
      characteristics of two different gel-free proteomic approaches to the
      fractionation of proteolytic peptides and intact proteins, respectively, in a
      first separation dimension. Separation and mass spectrometric detection by matrix
      assisted laser desorption/ionization tandem mass spectrometry (MALDI-MS/MS) were
      performed at the peptide level in both methods. Bottom-up analysis (BU) was
      carried out employing well established peptide fractionation in the first
      separation dimension by strong cation-exchange chromatography (SCX), followed by
      ion-pair reversed-phase chromatography (IP-RPC) in the second dimension. In the
      semi-top-down approach (STD), which involved intact protein fractionation in the
      first dimension, the separation mode in both dimensions was IP-RPC utilizing
      monolithic columns. Application of the two approaches to the proteome analysis of
      proteins extracted from a tumor tissue revealed that the BU method identified
      more proteins (1245 in BU versus 920 in STD) while STD analysis offered higher
      sequence coverage (14.8% in BU versus 17.5% in STD on average). The
      identification of more basic and larger proteins was slightly favored in the BU
      approach, most probably due to higher losses of these proteins during intact
      protein handling and separation in the STD method. A significant degree of
      complementarity was revealed by an approximately 33% overlap between one BU and
      STD replicate, while 33% each of the protein identifications were unique to both
      methods. In the STD method, peptides obtained upon digestion of the proteins
      contained in fractions of the first separation dimension covered a broad elution
      window in the second-dimension separation, which demonstrates a high degree of
      "pseudo-orthogonality" of protein and peptide separation by IP-RPC in both
      separation dimensions.

PMID- 20810123
TI  - High-temperature liquid chromatography inductively coupled plasma atomic emission
      spectrometry hyphenation for the combined organic and inorganic analysis of
      foodstuffs.
AB  - The coupling of a High-Temperature Liquid Chromatography system (HTLC) with an
      Inductively Coupled Plasma Atomic Emission Spectrometer (ICP-AES) is reported for
      the first time. This hyphenation combines the separation efficiency of HTLC with
      the detection power of a simultaneous ICP-AES system and allows the combined
      determination of organic compound and metals. The effluents of the column were
      introduced into the spectrometer and the chromatograms for organic compounds were
      obtained by plotting the carbon emission signal at a characteristic wavelength
      versus time. As regards metals, they were determined by injecting a small sample
      volume between the exit of the column and the spectrometer and taking the
      emission intensity for each one of the elements simultaneously. Provided that in
      HTLC the effluents emerged at high temperatures, an aerosol was easily generated
      at the exit of the column. Therefore, the use of a pneumatic nebulizer as a
      component of a liquid sample introduction system in the ICP-AES could be avoided,
      thus reducing the peak dispersion and limits of detection by a factor of two. The
      fact that a hot liquid stream was nebulized made it necessary to use a
      thermostated spray chamber so as to avoid the plasma cooling as a cause of the
      excessive mass of solvent delivered to it. Due to the similarity in sample
      introduction, an Evaporative Light Scattering Detector (ELSD) was taken as a
      reference. Comparatively speaking, limits of detection were of the same order for
      both HTLC-ICP-AES and HTLC-ELSD, although the latter provided better results for
      some compounds (from 10 to 20 mg L(-1) and 5-10 mg L(-1), respectively). In
      contrast, the dynamic range for the new hyphenation was about two orders of
      magnitude wider. More importantly, HTLC-ICP-AES provided information about the
      content of both organic (glucose, sucrose, maltose and lactose at concentrations
      from roughly 10 to 400 mg L(-1)) as well as inorganic (magnesium, calcium,
      sodium, zinc, potassium and boron at levels included within the 6-3000 mg L(-1))
      species. The new development was applied to the analysis of several food samples
      such as milk, cream, candy, isotonic beverage and beer. Good correlation was
      found between the data obtained for the two detectors used (i.e., ICP-AES and
      ELSD).

PMID- 20810124
TI  - Offline combination of pressurized fluid extraction and electron paramagnetic
      resonance spectroscopy for antioxidant activity of grape skin extracts
      assessment.
AB  - A comprehensive characterization of grape skin methanolic and ethanolic extracts
      prepared by pressurized fluid extraction (PFE) at various temperatures within 40
      to 120 degrees C from two wine grape varieties, St. Laurent and Alibernet was
      performed. For the first time, an offline combination of PFE and electron
      paramagnetic resonance (EPR) spectroscopy together with other experimental
      methods was employed to assess the effect of extraction conditions on numerous
      extract characteristics including antioxidant or radical-scavenging ability, HPLC
      profile of anthocyanins, total phenolic compounds content (TPC), tristimulus
      color values (CIE Lab), and pH values. The properties of extracts depend on the
      solvent used, the mass of grape skins as well as on the extraction conditions
      among which the temperature plays a crucial role. In spite of wide interval of
      extraction temperatures, all extracts still retain their antioxidant and/or
      radical-scavenging properties, indicating that the extracts prepared by PFE can
      serve as potential source of functional food supplements or color enhancers.

PMID- 20810125
TI  - High resolution N2 adsorption isotherms by graphitized carbon black and
      nongraphitized carbon black--alphas-curves, adsorption enthalpies and entropies.
AB  - The high resolution N(2) adsorption isotherms (77.4 K) by graphitized carbon
      blacks (GCB-I: A(BET)=54.2 m(2) g(-1) and GCB-II: A(BET)=69.4 m(2) g(-1)) and
      nongraphitized carbon black (NGCB: A(BET)=18.87 m(2) g(-1)) have been measured at
      p/p degrees =5*10(-8)-0.99. alpha(s)-Curve of the N(2) adsorption isotherm by GCB
      I is completely overlapped with that by GCB-II in the pressure range of p/p
      degrees =5*10(-6)-0.90, but the N(2)alpha(s)-curve by GCB-I is remarkably
      different from that by NGCB. The standard N(2)alpha(s)-data by GCB-I and NGCB
      have been determined in the range of alpha(s)=0.002-2.2. On the basis of the N(2)
      adsorption isotherms at the two temperatures (77.4 K, 87.3 K), the isosteric heat
      of adsorption (differential adsorption enthalpies), the differential adsorption
      entropies, and the integral adsorption entropies of N(2) molecules have been
      evaluated between theta (coverage)=0.05 and theta=1.50. The surface
      homogeneity/heterogeneity of carbon black samples has been discussed by the N(2)
      differential adsorption enthalpies. The adsorbed state of N(2) molecules on the
      carbon black surfaces has been considered by the differential and integral
      adsorption entropies.

PMID- 20810126
TI  - Conductivity and electrophoretic mobility of dilute ionic solutions.
AB  - Two complementary continuum theories of electrokinetic transport are examined
      with particular emphasis on the equivalent conductance of binary electrolytes.
      The "small ion" model [R.M. Fuoss, L. Onsager, J. Phys. Chem. 61 (1957) 668] and
      "large ion" model [R.W. O'Brien, L.R. White, J. Chem. Soc. Faraday Trans. 2 (74)
      (1978) 1607] are both discussed and the "large ion" model is generalized to
      include an ion exclusion distance and to account in a simple but approximate way
      for the Brownian motion of all ions present. In addition, the "large ion" model
      is modified to treat "slip" hydrodynamic boundary conditions in addition to the
      standard "stick" boundary condition. Both models are applied to the equivalent
      conductance of dilute KCl, MgCl(2), and LaCl(3) solutions and both are able to
      reproduce experimental conductances to within an accuracy of several tenths of a
      percent. Despite fundamental differences in the "small ion" and "large ion"
      theories, they both work equally well in this application. In addition, both
      "stick-large ion" and "slip-large ion" models are equally capable of accounting
      for the equivalent conductances of the three electrolyte solutions.

PMID- 20810127
TI  - Influence of crystallite size of nanophased hydroxyapatite on fibronectin and
      osteonectin adsorption and on MC3T3-E1 osteoblast adhesion and morphology.
AB  - The characteristic topographical features (crystallite dimensions, surface
      morphology and roughness) of bioceramics may influence the adsorption of proteins
      relevant to bone regeneration. This work aims at analyzing the influence of two
      distinct nanophased hydroxyapatite (HA) ceramics, HA725 and HA1000 on fibronectin
      (FN) and osteonectin (ON) adsorption and MC3T3-E1 osteoblast adhesion and
      morphology. Both substrates were obtained using the same hydroxyapatite
      nanocrystals aggregates and applying the sintering temperatures of 725 degrees C
      and 1000 degrees C, respectively. The two proteins used in this work, FN as an
      adhesive glycoprotein and ON as a counter-adhesive protein, are known to be
      involved in the early stages of osteogenesis (cell adhesion, mobility and
      proliferation). The properties of the nanoHA substrates had an important role in
      the adsorption behavior of the two studied proteins and clearly affected the
      MC3T3-E1 morphology, distribution and metabolic activity. HA1000 surfaces
      presenting slightly larger grain size, higher root-mean-square roughness (Rq),
      lower surface area and porosity, allowed for higher amounts of both proteins
      adsorbed. These substrates also revealed increased number of exposed FN cell
      binding domains as well as higher affinity for osteonectin. Regarding the
      osteoblast adhesion results, improved viability and cell number were found for
      HA1000 surfaces as compared to HA725 ones, independently of the presence or type
      of adsorbed protein. Therefore the osteoblast adhesion and metabolic activity
      seemed to be more sensitive to surfaces morphology and roughness than to the type
      of adsorbed proteins.

PMID- 20810128
TI  - Vertical wrinkling of the forehead or Procerus sign in Progressive Supranuclear
      Palsy.
AB  - 'Procerus sign' has been described as vertical wrinkles in the glabella region
      and bridge of the nose of patients with Progressive Supranuclear Palsy. The
      action of Corrugator and Orbicularis Oculi produce the vertical wrinkling. The
      relevance of this sign in early clinical diagnosis has been established and this
      sign has gained importance in literature and has been quoted as a useful sign in
      texts following the original description. We prospectively performed a cross
      sectional analysis of the facial appearance in subsequent Parkinsonism patients
      and found statistically significant presence of this sign in PSP compared to
      other Parkinsonian disorders. We recommend that this should be called "vertical
      wrinkling of the forehead" to avoid confusion and emphasize the dystonic nature
      of this condition rather than contraction of a single muscle as indicated by
      'Procerus sign'.

PMID- 20810129
TI  - How do we get better at identifying patients with atrial fibrillation who are at
      'truly low risk' or 'truly high risk' of stroke?

PMID- 20810130
TI  - Epistasis between HLA-DRB1 parental alleles in a Spanish cohort with multiple
      sclerosis.
AB  - BACKGROUND AND OBJECTIVE: Multiple sclerosis (MS) has been consistently
      associated with the HLA-DR2 haplotype and particularly with the HLA-DRB1*15
      allele. Epistatic interactions between both parental alleles in the DRB1 loci
      have been shown to modify the MS susceptibility risk. This study investigated the
      frequencies of various HLA-DRB1 genotypes, their impact on MS susceptibility and
      their correlation with the clinical severity in a Spanish population. METHODS: A
      genotype was considered as the combination of the two parental DRB1 alleles. We
      compared the frequencies of the genotypes in a sporadic MS population (n=380)
      with those of an unrelated healthy control cohort (n=1088). We correlated the
      different genotypes with the age at onset, gender distribution, symptoms at
      onset, course of the disease and progression severity by means of the time to
      reach the progressive phase and EDSS scores of 3 and 6. RESULTS: We found 81
      different genotypes. There were four different MS-predisposing genotypes. Three
      of them contained the DRB1*15 allele (DRB1*03/15, DRB1*04/15, and DRB1*08/15) and
      the fourth was homozygote for the DRB1*03 allele. The highest odds ratio was
      found with the genotype DRB1*08/15 (OR=3.88, 95% CI=1.83-8.26, p<0.01), followed
      by DRB1*03/03 (OR=3.15, 95% CI=1.93-5.14, p<0.01), DRB1*03/15 (OR=2.72, 95%
      CI=1.88-3.94, p<0.01) and DRB1*04/15 (OR=2.54, 95% CI=1.64-3.98, p<0.01). The
      DRB1*01/04 and the DRB1*15/15 genotypes were associated with a shorter time to
      reach an EDSS score of 6. CONCLUSIONS: Our results show the importance of
      epistatic interactions among the HLA-DRB1 alleles, modifying the risk for MS as
      well as its clinical severity.

PMID- 20810131
TI  - Clinicopathological characteristics of FTLD-TDP showing corticospinal tract
      degeneration but lacking lower motor neuron loss.
AB  - The presence of frontotemporal lobar degeneration with TDP-43-positive inclusions
      (FTLD-TDP) showing corticospinal tract (CST) degeneration but lacking lower motor
      neuron (LMN) loss has been reported, and the term primary lateral sclerosis (PLS)
      is used to distinguish motor neuron disease (MND) of these cases from amyotrophic
      lateral sclerosis (ALS). To date, however, details of clinicopathological
      findings of FTLD-MND-PLS type (FTLD-MND-P) have not been reported. We evaluated
      medical records and histopathological findings of ten cases of FTLD-MND-P, in
      comparison with those of six FTLD-MND-ALS type (FTLD-MND-A) cases. The mean age
      at onset and disease duration of FTLD-MND-P cases were 54 and 12 years,
      respectively. The first symptoms were frontotemporal dementia showing behavioral
      abnormality and/or personality change in five cases, semantic dementia in three
      cases, progressive non-fluent aphasia in one case, and auditory hallucination in
      one case. Upper motor neuron signs were clinically identified in six of the ten
      cases. There were no LMN signs throughout the clinical course in any case.
      Histopathologically, there was no obvious LMN loss or Bunina bodies in the
      hypoglossal nucleus or spinal cord in any case, whereas the CST was involved in
      all cases. The cerebral cortex of the six cases showed type 1 of TDP-43 histology
      defined by Cairns et al., whereas three cases showed type 3 histology, and one
      case showed type 2 histology. In all cases, TDP-43 positive neuronal cytoplasmic
      inclusions were absent or rare in the LMNs, while TDP-43 positive round
      structures were frequently identified in the neuropil of the spinal cord anterior
      horn in some cases. This study clarified that FTLD-MND-P cases have
      characteristic clinicopathological features distinct from those of FTLD-MND-A.

PMID- 20810132
TI  - A novel mitochondrial tRNAGlu (MTTE) gene mutation causing chronic progressive
      external ophthalmoplegia at low levels of heteroplasmy in muscle.
AB  - Mitochondrial respiratory chain defects are associated with diverse clinical
      phenotypes in both adults and children, and may be caused by mutations in either
      nuclear or mitochondrial DNA (mtDNA). We report the molecular genetic
      investigations of a patient with chronic progressive external ophthalmoplegia
      (CPEO) and myopathy where muscle biopsies taken 11 years apart revealed a
      progressive increase in the proportion of cytochrome c oxidase (COX)-deficient
      fibres. Mitochondrial genetic analysis of the early biopsy had seemingly excluded
      both mtDNA rearrangements and mtDNA point mutations. Sequencing mtDNA from
      individual COX-deficient muscle fibres in the second biopsy, however, identified
      an unreported m.14723T>C substitution within the mitochondrial tRNAGlu (MTTE)
      gene, which fulfilled all canonical criteria for pathogenicity. The m.14723T>C
      mutation was absent from several tissues, including muscle, from maternal
      relatives suggesting a de novo event, whilst quantitative analysis of the first
      muscle biopsy confirmed a very low level of the mutation (7% mutated mtDNA),
      highlighting a potential problem whereby pathogenic mtDNA mutations may remain
      undetected using established screening methodologies.

PMID- 20810133
TI  - Pronounced association of elevated serum homocysteine with stroke in subgroups of
      individuals: a nationwide study.
AB  - BACKGROUND: Although the original homocysteine hypothesis for atherothrombotic
      disease is falling out of favor, prior studies did not comprehensively adjust for
      confounders or explore specific subgroups of patients who may benefit from serum
      homocysteine-lowering. We aimed to determine (1) if elevated total homocysteine
      (tHcy) affects odds of prevalent stroke after adjusting for a broad array of
      pertinent covariates and (2) whether particular vascular risk factors amplify the
      effect of high homocysteine on prevalent stroke. METHODS: The independent and
      interactive effects of elevated tHcy (>=10 MUmol/L) on likelihood of prevalent
      stroke was assessed in the National Health and Nutrition Examination Survey, a
      nationally representative cross-sectional sample of the US population conducted
      from 1999 to 2004 (n=12,683). RESULTS: After adjusting for 17 covariates, those
      with elevated tHcy were more likely to have prevalent stroke vs. those without
      elevated tHcy (OR 1.52, 95% CI 1.01-2.29; p=0.045). Individuals with a
      combination of elevated tHcy and hypertension were substantially more likely to
      have prevalent stroke compared to individuals without either condition (OR 12.02,
      95% CI 6.36-22.73 for men and OR 17.34, 95% CI 10.49-28.64 for women). The
      association of tHcy with prevalent stroke was strongest in younger individuals
      and declined linearly with increasing age. CONCLUSIONS: Elevated tHcy
      independently increases odds of prevalent stroke. Younger individuals and those
      with concomitant hypertension may particularly benefit from tHcy-lowering.

PMID- 20810134
TI  - Dual origin of the left vertebral artery: extracranial MRA and CTA findings.
AB  - A 48-year-old man presented with a posterior circulation stroke secondary to left
      lateral medullary infarction. Contrast-enhanced magnetic resonance angiography
      (CEMRA) revealed 40-45% intracranial left vertebral artery stenosis, likely
      atherosclerotic in nature. CEMRA and subsequent computed tomography angiography
      also identified a duplicate origin of the left vertebral artery. The importance
      of recognition of this rare anatomical variant, its potential contribution to
      stroke aetiology, and the advantage of non-invasive vascular imaging prior to
      catheter angiography is emphasised.

PMID- 20810135
TI  - Phenolic glycosides from Agrimonia pilosa.
AB  - Phytochemical investigation of the methanolic extract from the aerial parts of
      Agrimonia pilosa led to the isolation of three compounds, (-)-aromadendrin 3-O
      beta-D-glucopyranoside, desmethylagrimonolide 6-O-beta-D-glucopyranoside, and 5,7
      dihydroxy-2-propylchromone 7-O-beta-D-glucopyranoside, together with nine known
      compounds, agrimonolide 6-O-glucoside, takanechromone C, astragalin, afzelin,
      tiliroside, luteolin, quercetin, isoquercetrin, and quercitrin. Their structures
      were determined by various spectroscopic analysis and chemical transformations.

PMID- 20810136
TI  - Metabolite profiling and quantification of phenolic compounds in methanol
      extracts of tomato fruit.
AB  - The consumption of tomatoes and tomato products has been associated with a
      reduction in the risk of contracting some types of cancer and other chronic
      diseases. These beneficial properties may be attributed to the presence of key
      metabolites and the interactions among them. We have developed and validated an
      analytical method for the comprehensive profiling of semi-polar metabolites in
      the methanol extract of three cultivars of raw tomatoes (Daniela, Raf and Rambo)
      grown in Almeria, in south-east Spain. Diode-array and time-of-flight/ion-trap
      mass spectrometry detectors were used to ensure the wide detection of metabolites
      with highly divergent properties. The masses thus detected were assigned by
      matching their accurate mass-signals with tomato compounds reported in the
      literature, and supplemented by UV and MS/MS information, reference compounds and
      existing metabolite databases. In this way we were able to identify tentatively
      135 compounds belonging to various structural classes, 21 of which are to our
      knowledge reported for the first time in the tomato fruit. Among the metabolites
      identified, the most abundant were phenolic compounds. This class of secondary
      metabolites is attracting considerable attention from producers and consumers due
      to their antioxidant activity and nutritional properties. Their quantitative
      analysis was achieved by using closely related derivatives for each family.

PMID- 20810137
TI  - Daphnane diterpenoids isolated from Trigonostemon thyrsoideum as HIV-1
      antivirals.
AB  - Four highly oxygenated daphnane diterpenoids, trigonothyrins D-G (1-4), were
      isolated from the stems of Trigonostemon thyrsoideum, and their structures were
      elucidated on the basis of extensive spectroscopic studies. Inhibitory activity
      against HIV-1 was assessed for compounds 1, 3 and 4, wherein, 3 showed activity
      with an EC(50) value of 0.13MUg/mL and a therapeutic index (TI) of 75.1.

PMID- 20810138
TI  - Differential quantification of cloned CVI988 vaccine strain and virulent RB-1B
      strain of Marek's disease viruses in chicken tissues, using real-time PCR.
AB  - The 'gold standard' vaccine against Marek's disease in poultry is the
      CVI988/Rispens virus, which is not easily distinguishable, antigenically or
      genetically, from virulent Marek's disease herpesvirus. Accurate differential
      measurement of the CVI988 vaccine and virulent viruses is important to
      investigate mechanisms of vaccinal protection. Minimal sequence differences
      between CVI988 and virulent MDV strains restrict the application of molecular
      diagnostic methods such as real-time PCR to distinguish between these viruses.
      The use of bacterial-artificial-chromosome (BAC) cloned CVI988 virus, which
      carries the BAC vector sequences in place of the U(s)2 gene, allows its
      differential quantification from virulent strains using real-time PCR assays that
      target the BAC vector sequence and the U(S)2 gene respectively. These novel
      assays allowed investigation of replication of both serotype-1 vaccine virus
      (cloned CVI988) and challenge virus (RB-1B strain) in tissues of individual
      chickens in an experimental vaccination-challenge model of Marek's disease.

PMID- 20810139
TI  - Detection and molecular characterization of Theileria sp. in fallow deer (Dama
      dama) and ticks from an Italian natural preserve.
AB  - The prevalence of piroplasms in a closed population of fallow deer (Dama dama L.)
      living in the Italian preserve of "Bosco della Mesola"--Ferrara (Mesola wood) was
      investigated. Blood samples and ticks were collected from 62 fallow deer. On
      microscopic observation, 28 (45.0%) blood samples were positive for piroplasms
      while PCR provided evidence for piroplasms infection in 47 (75.8%) fallow deer.
      The 67 ticks, collected from positive and negative animals, were identified as
      Ixodesricinus L., 1758 (89.6%) and Haemaphysalisconcinna Koch, 1844 (10.4%). At
      the PCR, four samples of I. ricinus were positive for piroplasms. The sequences
      of the 18S rRNA gene from both blood and ticks were identical and showed high
      identity (99.6%) with Theileria sp. 3185/02 (DQ866842) and Theileria capreoli
      (AY726011) from roe deer. Interestingly, the phylogenetical analyses evidenced
      differences between the Theileria strain from Mesola wood and the ones isolated
      in fallow deer from other Italian areas.

PMID- 20810140
TI  - [Jaw osteonecrosis induced by oral biphosphonates: 12 cases].
AB  - INTRODUCTION: The incidence of jaw osteonecrosis induced by oral or intravenous
      biphosphonates (BP) has been increasing. Two hundred cases of jaw osteonecrosis
      induced by oral BP (JONOBP) were reported, with an incidence of 4 % and a
      prevalence of 1/952. We report 12 cases of JONOBP observed from January 2007 to
      January 2009. MATERIAL AND METHODS: A pluridisciplinary committee including
      odontologists, stomatologists, and maxillofacial surgeons from two Paris
      hospitals was asked to manage patients treated by BP. Twelve patients presenting
      with JONOBP were included from January 2007 to January 2009. For each of these
      patients, age, sex, associated co-morbidities, any triggering factor, previous or
      current combination treatments, the type of BP used, its initial indication,
      dosage, delay before onset of JONOBP, and delay between first clinical signs and
      diagnosis were studied. JONOBP localization, stage (American Association of Oral
      and Maxillofacial Surgeons [AAOMS] classification), clinical and radiological
      signs, anatomopathological and bacteriological examinations (when performed) were
      documented. The treatment and evolution were described. RESULTS: Ten women and
      two men, mean age 65 years (36 to 82 years), were included. BP were taken orally
      once a week or daily. The mean duration of BP exposure was 39.6+/-2,4 months (19
      to 58 months). The indication for BP was prevention or treatment of osteoporosis
      in 11 cases and breast with bone metastases in one case. Tooth extraction was the
      triggering factor in nine cases. The premolar and molar mandibular area was the
      most often affected. Corticosteroid therapy was combined to BP in half of the
      cases. There were no clinical, radiological, and histological specific signs. BP
      treatment was stopped in all patients. Nine patients underwent surgery. Evolution
      was favorable for nine patients. Six patients were cured, on average 3.8 months
      after beginning management (one to nine months). Three male patients improved.
      Three female patients were lost to follow-up. Alendronate was the most frequently
      implicated (six cases) and risedronate (five cases). Five patients presented with
      diagnosed or suspected auto-immune conditions. DISCUSSION: The duration of
      exposure to BP was superior to three years in most cases. The triggering factor
      was tooth extraction. The mean diagnostic delay was five months. There were more
      stage 2 and 3 patients, according to the AAOMS classification. They were the most
      frequent, probably because of the higher number of co-morbidities, especially
      corticosteroid intake. Patient management complied to Afssaps and AAOMS
      recommendations. The evolution was favorable for all managed patients.

PMID- 20810141
TI  - Extracellular matrix remodelling in rat endometrium during early pregnancy: the
      role of fibronectin and laminin.
AB  - The endometrial extracellular matrix (ECM) remodelling has a crucial role in the
      establishment of a successful pregnancy. In addition to its basic function such
      as regulation of cell function, differentiation, migration, proliferation, the
      substantial alterations in the endometrial ECM may play a specific role in the
      trophoblast invasion, placentation, cell death and formation of the proper and
      functional implantation chamber around the embryo. In the present study,
      immunolocalizations of fibronectin and laminin were determined using avidin
      biotin complex-peroxidase in rat implantation sites during 7-10 days of
      pregnancy. Both proteins were present in the basal membrane of blood vessels and
      in decidual matrix whereas they were absent or had very weak reactivity in the
      primary decidual zone on day 7. When placentation has begun, the immunoreactivity
      of both proteins was increased in the placental bed and in the basal membrane of
      blood vessels of the mesometrial region. The immunolocalization of both proteins
      seemed to be decreased in the antimesometrial decidua, however, it was increased
      in the mesometrial decidual matrix on days 9 and 10. Therefore, it could be
      suggested laminin and fibronectin demonstrating dynamic expressions in relation
      with the morphological differentiation of endometrial stroma may play crucial
      roles in the control of trophoblast adhesion and invasion, in placentation and
      angiogenesis, in the determination of cell shape and fate thus contributing the
      endometrial receptivity and a successful pregnancy.

PMID- 20810142
TI  - Expansion of human articular chondrocytes and formation of tissue-engineered
      cartilage: a step towards exploring a potential use of matrix-induced cell
      therapy.
AB  - Monolayer culture expansion remains as a fundamental step to acquire sufficient
      number of cells for 3D constructs formation. It has been well-documented that
      cell expansion is however accompanied by cellular dedifferentiation. In order to
      promote cell growth and circumvent cellular dedifferentiation, we evaluated the
      effects of Transforming Growth Factor Beta-2 (TGF-beta2), Insulin-like Growth
      Factor-I (IGF-I) and basic Fibroblast Growth Factor (bFGF) combination on
      articular chondrocytes culture and 'chondrocytes-fibrin' construct formation.
      Chondrocytes were serially cultured in: (1) F12:DMEM+10% Foetal Bovine Serum
      (FBS) with growth factors (FD10GFs), (2) F12:DMEM+2%FBS with the growth factors
      (FD2GFs) and, (3) F12:DMEM+10%FBS without growth factors (FD) as control.
      Cultured chondrocytes were evaluated by means of growth kinetics parameters, cell
      cycle analysis, quantitative phenotypic expression of collagen type II, aggrecan
      core protein sox-9 and collagen type I and, immunochemistry technique. Harvested
      chondrocytes were incorporated with plasma-derived fibrin and were polymerized to
      form the 3D constructs and implanted subcutaneously at the dorsum of athymic nude
      mice for eight (8) weeks. Resulted constructs were assigned for gross inspections
      and microscopic evaluation using standard histochemicals staining,
      immunochemistry technique and, quantitative phenotypic expression of cartilage
      markers to reassure cartilaginous tissue formation. Growth kinetics performance
      of chondrocytes cultured in three (3) types of culture media from the most to
      least was in the following order: FD10GFs>FD2GFs>FD. Following growth kinetics
      analysis, we decided to use FD10GFs and FD (control) for further evaluation and
      'chondrocytes-fibrin' constructs formation. Chondrocytes cultured in FD10GFs
      preserved the normal diploid state (2c) with no evidence of aneuploidy, haploidy
      or tetraploidy. Expression of cartilage-specific markers namely collagen type II,
      aggrecan core protein and sox-9 were significantly higher in FD10GFs when
      compared to control. After implantation, 'chondrocytes-fibrin' constructs
      exhibited firm, white, smooth and glistening cartilage-like properties. FD10GFs
      constructs formed better quality cartilage-like tissue than FD constructs in term
      of overall cartilaginous tissue formation, cells organization and extracellular
      matrix distribution in the specimens. Cartilaginous tissue formation was
      confirmed by the presence of lacunae and cartilage-isolated cells embedded within
      basophilic ground substance. Presence of proteoglycan was confirmed by positive
      Safranin O staining. Collagen type II exhibited immunopositivity at the
      pericellular and inter-territorial matrix area. Chondrogenic properties of the
      construct were further confirmed by the expression of genes encoding collagen
      type II, aggrecan core protein and sox9. In conclusion, FD10GFs promotes the
      proliferation of chondrocytes and formation of good quality 'chondrocytes-fibrin'
      constructs which may have potential use of matrix-induced cell implantation.

PMID- 20810143
TI  - Influence of cell packing by centrifugation on 40-MHz ultrasound backscatter.
AB  - High-frequency ultrasound (HFUS) signals backscattered from RBL-2H3 cell pellets
      prepared under different centrifugal forces were analyzed to investigate the
      packing effect of cell aggregates. The measurements were performed in a pulse
      echo setup with a 40-MHz transducer. The changes of ultrasound signals from cell
      pellet in backscattered power, statistical parameter, and pellet thickness were
      monitored after centrifugation at between 100g and 1600g. Experimental results
      showed that the HFUS backscattered power from cell pellets was inversely
      proportional to centrifugal force and increased to a plateau within 1-2h after
      centrifugation. The initial thickness of cell pellets decreased with higher
      centrifugal force, but the changes in thickness and time that took to reach a
      plateau increased at higher centrifugal force. The envelope statistics of
      backscattered signals with Nakagami distribution indicates that the centrifugal
      force and elapsed time after centrifugation affected the backscattering
      characteristics. The present study suggests that centrifugal force and data
      acquisition time after cell pellet formation should be considered in in vitro
      cell packing method with centrifugation to emulate the tissue in vivo.

PMID- 20810144
TI  - Antimicrobial resistance of fecal indicators in municipal wastewater treatment
      plant.
AB  - Antimicrobial resistance of fecal coliforms (n = 153) and enterococci (n = 199)
      isolates was investigated in municipal wastewater treatment plant (WWTP) based on
      activated sludge system. The number of fecal indicators (in influent and effluent
      as well as in the aeration chamber and in return activated sludge mixture) was
      determined using selective media. Susceptibility of selected strains was tested
      against 19 (aminoglycosides, aztreonam, carbapenems, cephalosporins, beta
      lactam/beta-lactamase inhibitors, fluoroquinolones, penicillines, tetracycline
      and trimethoprim/sulfamethoxazole) and 17 (high-level aminoglycosides,
      ampicillin, chloramphenicol, erythromycin, fluoroquinolones, glycopeptides,
      linezolid, lincosamides, nitrofuration, streptogramins, tetracycline)
      antimicrobial agents respectively. Among enterococci the predominant species were
      Enterococcus faecium (60.8%) and Enterococcus faecalis (22.1%), while remaining
      isolates belonged to Enterococcus hirae (12.1%), Enterococcus
      casseliflavus/gallinarum (4.5%), and Enterococcus durans (0.5%). Resistance to
      nitrofuration and erythromycin was common among enterococci (53% and 44%,
      respectively), and followed by resistance to ciprofloxacin (29%) and tetracycline
      (20%). The resistance phenotypes related to glycopeptides (up to 3.2%) and high
      level aminoglycosides (up to 5.4%) were also observed. Most frequently, among
      Escherichia coli isolates the resistance patterns were found for ampicillin
      (34%), piperacillin (24%) and tetracycline (23%). Extended-spectrum beta
      lactamase producing E. coli was detected once, in the aeration chamber. In the
      study the applied wastewater treatment processes considerably reduced the number
      of fecal indicators. Nevertheless their number in the WWTP effluent was higher
      than 10(4) CFU per 100 ml and periodically contained 90% of bacteria with
      antimicrobial resistance patterns. The positive selection of isolates with
      antimicrobial resistance patterns was observed during the treatment processes.
      Substantial concern should be paid to the isolates resistant to 3 or more
      chemical classes of antimicrobials (MAR). In treated wastewater MAR E. coli and
      MAR enterococci constituted respectively 9% and 29% of tested isolates.

PMID- 20810145
TI  - Structural diversity of organochlorine compounds in groundwater affected by an
      industrial point source.
AB  - Groundwater samples contaminated by an industrial point source were analysed in
      order to reveal the structural diversity of halogenated organic contaminants.
      Particular focus was laid on the metabolites and derivatives related to the
      pesticides DDT (2,2-bis(chlorophenyl)-1,1,1-trichlorethane) and lindane (gamma
      hexachlorocyclohexane). Additionally, a wide range of chlorinated and brominated
      xenobiotics were identified. These results represent a high degree of
      contamination with organochlorine compounds illustrating a considerable
      structural diversity in groundwater in the vicinity of the industrial plant. The
      polar DDT-metabolite DDA (2,2-bis(chlorophenyl)acetic acid), which has been
      neglected in water studies widely, represents the main DDT metabolite analysed in
      the water samples. Besides DDA, some unknown substances with structural relation
      to DDA and DDT were detected and identified, in detail 2,2-bis(4
      chlorophenyl)acetic acid N-methyl amide (DDAMA) and 2,2-bis(4-chlorophenyl)acetic
      acid n-butyl ester (DDABE). As an overall implication of this study it has to be
      demanded that analysis of industrially affected ground waters have to be based on
      screening analysis for a comprehensive view on the state of pollution.

PMID- 20810146
TI  - Trophic structure and mercury distribution in a Gulf of St. Lawrence (Canada)
      food web using stable isotope analysis.
AB  - Even at low concentrations in the environment, mercury has the potential to
      biomagnify in food chains and reaches levels of concern in apex predators. The
      aim of this study was to relate the transfer of total mercury (THg) and
      methylmercury (MeHg) in a Gulf of St. Lawrence food web to the trophic structure,
      from primary consumers to seabirds, using stable nitrogen (delta(15)N) and carbon
      (delta(13)C) isotope analysis and physical environmental parameters. The energy
      reaching upper trophic level species was principally derived from pelagic primary
      production, with particulate organic matter (POM) at the base of the food chain.
      We developed a biomagnification factor (BMF) taking into account the various prey
      items consumed by a given predator using stable isotope mixing models. This BMF
      provides a more realistic estimation than when using a single prey. Lipid
      content, body weight, trophic level and benthic connection explained 77.4 and
      80.7% of the variation in THg and MeHg concentrations, respectively in this food
      web. When other values were held constant, relationships with lipid and benthic
      connection were negative whereas relationships with trophic level and body weight
      were positive. Total Hg and MeHg biomagnified in this food web with
      biomagnification power values (slope of the relationship with delta(15)N) of
      0.170 and 0.235, respectively on wet weight and 0.134 and 0.201, respectively on
      dry weight. Values of biomagnification power were greater for pelagic and
      benthopelagic species compared to benthic species whereas the opposite trend was
      observed for levels at the base of the food chain. This suggests that Hg would be
      readily bioavailable to organisms at the base of the benthic food chain, but
      trophic transfer would be more efficient in each trophic level of pelagic and
      benthopelagic food chains.

PMID- 20810147
TI  - Fluidized bed ash and passive treatment reduce the adverse effects of acid mine
      drainage on aquatic organisms.
AB  - Elevated concentrations of acidity and metals in acid mine drainage (AMD) may be
      effectively addressed by active and passive treatment technologies. However,
      typical evaluations consider only chemical water quality with little if any
      regard for biological metrics. Robust evaluations including both chemical and
      biological indicators of water quality improvement are needed. In this study,
      injection of alkaline fluidized bed ash (FBA) into a flooded underground coal
      mine was coupled with a five-cell passive treatment system to ameliorate an
      abandoned AMD discharge in eastern Oklahoma. The passive system included process
      units promoting both aerobic and anaerobic treatment mechanisms. Resulting water
      quality changes and biological responses were evaluated. Organisms of two
      distinct functional groups (the filter-feeding mollusk Corbicula fluminea and the
      wide-spectrum feeding fish Lepomis macrochirus) were exposed to mine waters in
      several treatment cells. The combination of treatment technologies was
      hypothesized to limit potential negative effects on these aquatic organisms.
      Tissues were harvested and analyzed for concentrations of several metals (Al, Fe,
      Mn, Mg, Ca, Ni, Cu and Zn) of interest. Organismal responses, such as
      hepatosomatic index, condition factor, and condition index, did not vary
      significantly among organisms exposed within different treatment cells when
      compared to non-AMD impaired waters. Metal tissue accumulation trends, compared
      to aqueous concentrations, were observed for Fe, Ni and Zn. Exposure experiments
      with these two organisms indicated that FBA introductions coupled with passive
      treatment decreased the potential adverse effects of AMD to biological systems.

PMID- 20810148
TI  - Analysis of composition, distribution and origin of hexachlorocyclohexane
      residues in agricultural soils from NW Spain.
AB  - Concentrations of the isomers of the organochlorine pesticide
      hexachlorocyclohexane (HCH) were determined in 252 surface soil samples collected
      within a sampling network covering agricultural areas in Galicia (NW Spain). The
      concentration of total HCH (sum of alpha+beta+gamma+delta) ranged between 4 and
      2305ngg(-)1 (dry weight), with the alpha-HCH and gamma-HCH isomers predominating
      (<1-1404ngg(-)1 and <1-569ngg(-)1, respectively). The distribution of the
      pesticide residues was very heterogeneous, with the largest concentrations
      present in one of the studied areas (the province of A Coruna). The distribution
      of HCH was not found to be related to any soil property (organic matter, pH,
      clays, and metals). Multivariate statistical analysis of the data revealed that
      three populations of samples with a defined composition of HCH, can be related to
      the source of HCH: technical HCH (alpha/gamma>3), lindane (99% gamma-HCH), or
      both. The existence of a third population consisting almost exclusively of alpha
      HCH suggests that background contamination of anthropogenic origin dates from
      several decades ago. The detailed analysis of these populations enabled the
      possible temporal scale of the application of these pesticides to be deduced.

PMID- 20810149
TI  - Remediation of petroleum contaminated soils by joint action of Pharbitis nil L.
      and its microbial community.
AB  - The plot-culture experiments were conducted for examining the feasibility of
      Pharbitis nil L. and its microbial community to remedy petroleum contaminated
      soils. The petroleum contaminated soil, containing 10% (w/w) of the total
      petroleum hydrocarbons (TPHs), was collected from the Shengli Oil Field, Dongying
      City, Shandong Province, China. The collected soil was applied and diluted to a
      series of petroleum contaminated soils (0.5%, 1.0%, 2.0% and 4.0%). Root length,
      microbial populations and numbers in the rhizosphere were also measured in this
      work. The results showed that there was significantly (p<0.05) greater
      degradation rate of TPHs in vegetated treatments, up to 27.63-67.42%, compared
      with the unvegetated controls (only 10.20-35.61%), after a 127-day incubation.
      Although various fractions of TPHs had an insignificant concentration difference
      due to the presence of the remediation plants, there was a much higher removal of
      saturated hydrocarbon compared with other components. The biomass of P. nil L.
      did not decrease significantly when the concentration of petroleum hydrocarbons
      in soil was <=2.0%. The trends of microbial populations and numbers in the
      rhizosphere were similar to the biomass changes, with the exception that fungi at
      0.5% petroleum contaminated soil had the largest microbial populations and
      numbers.

PMID- 20810151
TI  - Knowledge of the D-dimer test result influences clinical probability assessment
      of pulmonary embolism.
AB  - BACKGROUND: In patients with suspected pulmonary embolism (PE), an unlikely or
      non-high probability assessment combined with a normal D-dimer test can safely
      exclude the diagnosis. We studied the influence of early D-dimer knowledge on
      clinical probability assessment. METHODS: A questionnaire was sent to 150
      randomly selected pulmonologists and internists in the Netherlands, presenting
      six hypothetical case-descriptions of patients with suspected PE. Physicians were
      randomized to receive one of three versions. The version contained a normal, an
      abnormal or no D-dimer result with each case-description. Each version contained
      two cases with an abnormal D-dimer result, two cases with a normal D-dimer result
      and two cases with no D-dimer result. RESULTS: A total of 71 physicians (47%)
      returned the questionnaire; the three versions were equally represented. Compared
      to the control cases in which no D-dimer was given, knowledge of an abnormal D
      dimer resulted in more "likely" clinical scores using the Wells' score (absolute
      increase in "likely" of 25-37%, p=0.005, 0.111 and 0.144), while knowledge of a
      normal D-dimer resulted in more "unlikely" scores (absolute increase in
      "unlikely" of 27-44%, p=0.001 and 0.070). D-dimer knowledge did not influence the
      probability assessment when the clinical suspicion was very high. CONCLUSION:
      Knowledge of the D-dimer test influences the physician in how the clinical
      probability for PE is scored. This will have direct clinical consequences, such
      as unnecessary imaging testing or inappropriate exclusion of the diagnosis.
      Physicians should therefore make sure that they examine the patient before they
      take notice of the D-dimer test result.

PMID- 20810150
TI  - Visually observed mold and moldy odor versus quantitatively measured microbial
      exposure in homes.
AB  - The main study objective was to compare different methods for assessing mold
      exposure in conjunction with an epidemiologic study on the development of
      children's asthma. Homes of 184 children were assessed for mold by visual
      observations and dust sampling at child's age 1 (Year 1). Similar assessment
      supplemented with air sampling was conducted in Year 7. Samples were analyzed for
      endotoxin, (1-3)-beta-D-glucan, and fungal spores. The Mold Specific Quantitative
      Polymerase Chain Reaction assay was used to analyze 36 mold species in dust
      samples, and the Environmental Relative Moldiness Index (ERMI) was calculated.
      Homes were categorized based on three criteria: 1) visible mold damage, 2) moldy
      odor, and 3) ERMI. Even for homes where families had not moved, Year 7 endotoxin
      and (1-3)-beta-d-glucan exposures were significantly higher than those in Year 1
      (p<0.001), whereas no difference was seen for ERMI (p=0.78). Microbial
      concentrations were not consistently associated with visible mold damage
      categories, but were consistently higher in homes with moldy odor and in homes
      that had high ERMI. Low correlations between results in air and dust samples
      indicate different types or durations of potential microbial exposures from dust
      vs. air. Future analysis will indicate which, if any, of the assessment methods
      is associated with the development of asthma.

PMID- 20810152
TI  - The history of urology in Cleveland, Ohio.
AB  - INTRODUCTION: Urology in Cleveland, as in the rest of the country, has evolved
      greatly over the past century. The recent passing of Resnick and Novick warrants
      a review of Cleveland's rich urological history. MATERIALS AND METHODS: We
      reviewed historical and scientific literature and interviewed Cleveland
      urologists. RESULTS: Lower joined his cousin Crile as professor at Case Western
      Reserve University (CWRU) before they cofounded the Cleveland Clinic (CC) in
      1921. Goldblatt at CWRU discovered renovascular hypertension, leading Poutasse at
      CC to develop renovascular arteriography and bypass surgery. Kolff brought his
      greatest invention, dialysis, to the United States when he joined CC. Straffon
      put CC's renal transplant program on the map through his success with deceased
      donor transplants. Persky, renowned at radical prostatectomies, chaired urology
      at CWRU for nearly 30 years and trained 6 future university department
      chairpersons. Resnick succeeded him and became one of the eminent figures in
      urology; an authority on numerous subjects, president of the American Urological
      Association and American Board of Urology (ABU) and Editor of the Journal of
      Urology. Novick, who became chairman at CC in 1985, was the consummate renal
      surgeon; he was adept at renal revascularization and transplantation, but his
      greatest surgical innovation was the partial nephrectomy. He likewise held many
      positions, including president of the ABU. CONCLUSIONS: Cleveland has been a
      driving force in the evolution of urology in the last century. Resnick and Novick
      led a golden age of urology for several decades until their recent untimely
      passings.

PMID- 20810153
TI  - Safety and efficacy of measles, mumps, and rubella vaccine in patients with
      DiGeorge syndrome.

PMID- 20810154
TI  - Fatal consequence of allergic rhinitis.

PMID- 20810155
TI  - Mepolizumab as a corticosteroid-sparing agent in lymphocytic variant
      hypereosinophilic syndrome.
AB  - BACKGROUND: Mepolizumab, a monoclonal anti-IL-5 antibody, is an effective
      corticosteroid-sparing agent for patients with Fip1-like 1/platelet-derived
      growth factor receptor alpha fusion (F/P)-negative hypereosinophilic syndrome
      (HES). Lymphocytic variant hypereosinophilic syndrome (L-HES) is characterized by
      marked overproduction of IL-5 by dysregulated T cells. OBJECTIVE: To determine
      whether patients with L-HES respond to mepolizumab in terms of corticosteroid
      tapering and eosinophil depletion to the same extent as corticosteroid-responsive
      F/P-negative patients with HES and a normal T-cell profile. METHODS: Patients
      enrolled in the mepolizumab trial were evaluated for L-HES on the basis of T-cell
      phenotyping and T-cell receptor gene rearrangement patterns, and their serum
      thymus-and-activation-regulated chemokine (TARC) levels were measured. Response
      to treatment was compared in patient subgroups based on results of these
      analyses. RESULTS: Lymphocytic variant HES was diagnosed in 13 of 63 patients
      with HES with complete T-cell assessments. The ability to taper corticosteroids
      on mepolizumab was similar in patients with L-HES and those with a normal T-cell
      profile, although a lower proportion of patients with L-HES maintained eosinophil
      levels below 600/MUL. Increased serum TARC levels (>1000 pg/mL) had no
      significant impact on the ability to reduce corticosteroid doses, but a lower
      proportion of patients with elevated TARC achieved eosinophil control on
      mepolizumab. CONCLUSION: Mepolizumab is an effective corticosteroid-sparing agent
      for patients with L-HES. In some cases however, eosinophil levels remain above
      600/MUL, suggesting incomplete neutralization of overproduced IL-5 or involvement
      of other eosinophilopoietic factors.

PMID- 20810156
TI  - ALOX5AP and LTA4H polymorphisms modify augmentation of bronchodilator
      responsiveness by leukotriene modifiers in Latinos.
AB  - BACKGROUND: Understanding the effects of interactions between multiple genes and
      asthma medications may aid in the understanding of the heterogeneous response to
      asthma therapies. OBJECTIVE: To identify modulating effects of arachidonate 5
      lipoxygenase-activating protein (ALOX5AP) and leukotriene A(4) hydrolase (LTA4H)
      gene polymorphisms on the drug-drug interaction between leukotriene modifiers and
      albuterol in Mexicans and Puerto Ricans. METHODS: In a cross-sectional study of
      293 Mexicans and 356 Puerto Ricans with asthma, ALOX5AP and LTA4H genes were
      sequenced, and interactions between gene polymorphisms and bronchodilator
      responsiveness to albuterol were compared between leukotriene modifier users and
      nonusers. RESULTS: In heterozygotes and homozygotes for the minor allele at LTA4H
      single nucleotide polymorphism (SNP) rs2540491 and heterozygotes for the major
      allele at LTA4H SNP rs2540487, leukotriene modifier use was associated with a
      clinically significant increase in percent change in FEV(1) after albuterol
      administration of 7.10% (P = .002), 10.06% (P = .001), and 10.03% (P < .001),
      respectively. Presence of the major allele at ALOX5AP SNP rs10507391 or the minor
      allele at ALOX5AP SNP rs9551963 augmented this response. When stratified by
      ethnicity, these findings held true for Puerto Ricans but not Mexicans.
      CONCLUSION: LTA4H and ALOX5AP gene polymorphisms modify the augmentation of
      bronchodilator responsiveness by leukotriene modifiers in Puerto Ricans but not
      Mexicans with asthma.

PMID- 20810157
TI  - Presence of IL-5 protein and IgE antibodies to staphylococcal enterotoxins in
      nasal polyps is associated with comorbid asthma.
AB  - BACKGROUND: Nasal polyps often are associated with asthma. The phenotype of these
      patients is unknown. OBJECTIVE: To identify the mucosal factors associated with
      asthma comorbidity, we analyzed the inflammatory patterns of nasal polyps.
      METHODS: Nasal polyps from 70 Belgian patients, 34% with asthma, were analyzed
      for type of inflammation, T-cell cytokines, and IgE antibodies to Staphylococcus
      aureus enterotoxins. The same investigations were repeated in 93 Chinese patients
      with polyps, a group with a low asthma comorbidity rate (8%). RESULTS: In Belgian
      patients with polyps, 54% of samples showed eosinophilic inflammation. A
      classification tree evaluation identified IL-5 as the main positive determinant.
      Enterotoxin IgE in tissue (37%) was associated with significantly increased total
      IgE and eosinophil cationic protein concentrations. Expression of enterotoxin
      IgE, total IgE at greater than 1,442 kU/L, and eosinophil cationic protein at
      greater than 17,109 MUg/L in samples with a total IgE concentration of greater
      than 246 kU/L significantly predicted asthma (odds ratio, 5.8-13). Only 7.5% of
      the samples from Chinese patients with polyps showed eosinophilic inflammation.
      IL-5 was confirmed as a positive determinant of eosinophilic inflammation, and
      enterotoxin IgE in tissue (17% of patients) was associated with significantly
      increased total IgE and eosinophil cationic protein concentrations. The
      expression of IL-5 or total IgE at greater than 790 kU/L in samples with an IL-5
      concentration of greater than 194 pg/mL significantly predicted comorbid asthma
      (odds ratio, 17.2-96). CONCLUSION: Mucosal inflammation in nasal polyps
      orchestrated by T(H)2 cytokines and amplified by S aureus enterotoxins is
      characterized by an increased eosinophilic inflammation and formation of IgE
      antibodies. This phenotype is associated with comorbid asthma in white and Asian
      patients with nasal polyps.

PMID- 20810158
TI  - Successful engraftment of donor marrow after allogeneic hematopoietic cell
      transplantation in autosomal-recessive hyper-IgE syndrome caused by dedicator of
      cytokinesis 8 deficiency.

PMID- 20810159
TI  - Apolipoprotein A-IV is a candidate target molecule for the treatment of seasonal
      allergic rhinitis.
AB  - BACKGROUND: Allergic rhinitis is a global health problem that causes major
      illnesses and disability worldwide. Allergen-specific immunotherapy (SIT) is the
      only available treatment that can alter the natural course of allergic disease.
      However, the precise mechanism underlying allergen-SIT is not well understood.
      OBJECTIVE: The aim of the current study was to identify protein expression
      signatures reflective of allergen-SIT-more specifically, sublingual immunotherapy
      (SLIT). METHODS: Serum was taken twice from patients with seasonal allergic
      rhinitis caused by Japanese cedar: once before the pollen season and once during
      the season. A total of 25 patients was randomly categorized into a placebo
      treated group and an active-treatment group. Their serum protein profiles were
      analyzed by 2-dimensional electrophoresis. RESULTS: Sixteen proteins were found
      to be differentially expressed during the pollen season. Among the differentially
      expressed proteins, the serum levels of complement C4A, apolipoprotein A-IV (apoA
      IV), and transthyretin were significantly increased in SLIT-treated patients but
      not in placebo-treated patients. Among these proteins, the serum levels of apoA
      IV correlated with the clinical symptom-medication scores (r = -0.635; P < .05)
      and with quality of life scores (r = -0.516; P < .05) in the case of SLIT-treated
      patients. The amount of histamine released from the basophils in vitro was
      greatly reduced after the addition of recombinant apoA-IV in the medium (P <
      .01). CONCLUSION: Our data will increase the understanding of the mechanism of
      SLIT and may provide novel insights into the treatment of allergic rhinitis.

PMID- 20810160
TI  - Spatiotemporal dynamics of speech sound perception in chronic developmental
      stuttering.
AB  - High-density ERPs were recorded in eight adults with persistent developmental
      stuttering (PERS) and eight matched normally fluent (CONT) control volunteers
      while participants either repeatedly uttered the vowel 'ah' or listened to their
      own previously recorded vocalizations. The fronto-central N1 auditory wave was
      reduced in response to spoken vowels relative to heard vowels (auditory-vocal
      gating), but no difference in the extent of such modulation was found in the PERS
      group. Abnormalities in the PERS group were restricted to the LISTEN condition,
      in the form of early N1 and late N3 amplitude changes. Voltage of the N1 wave was
      significantly reduced over right inferior temporo-occipital scalp in the PERS
      group. A laterality index derived from N1 voltage moderately correlated with the
      PERS group's assessed pre-experiment stuttering frequency. Source localization
      with sLORETA (Pascual-Marqui, R. D. (2002). Standardized low-resolution brain
      electromagnetic tomography (sLORETA): Technical details. Methods & Findings in
      Experimental & Clinical Pharmacology, 24, 5-12.) revealed that at the peak of the
      N1 the PERS group displayed significantly greater current density in right
      primary motor cortex than the CONT group, suggesting abnormal early speech-motor
      activation. Finally, the late N3 wave was reduced in amplitude over inferior
      temporo-occipital scalp, more so over the right hemisphere. sLORETA revealed that
      in the time window of the N3 the PERS group showed significantly less current
      density in right secondary auditory cortex than the CONT group, suggesting
      abnormal speech sound perception. These results point to a deficit in auditory
      processing of speech sounds in persistent developmental stuttering, stemming from
      early increased activation of right rolandic area and late reduced activation in
      right auditory cortex.

PMID- 20810161
TI  - Romantic partner selection and socialization of young adolescents' substance use
      and behavior problems.
AB  - This study examined romantic partner selection and socialization of substance use
      (cigarettes, alcohol) and behavior problems among a sample of 78 young
      adolescents (6th-8th graders) over eleven months. Adolescent and romantic partner
      behaviors were assessed before and after relationships were initiated via school
      records and self-report. Most selection and socialization effects were apparent
      for the eighth grade adolescents (at Time 1). Prior to their relationship, eighth
      graders and romantic partners were alike on alcohol use. In contrast, romantic
      socialization effects emerged for eighth graders' cigarette use and behavior
      problems. The nature of the partner socialization effects depended on the
      combination of adolescents' and partners' pre-relationship behaviors. Eighth
      graders who dated partners with fewer problems showed the greatest instability in
      their behavior problems and partner behavior predicted greater decreased in
      problem behaviors among adolescents with more problems. The implications of these
      findings are discussed within the broader context of adolescent peer
      relationships.

PMID- 20810162
TI  - The characteristics of in vitro biological activity of titanium surfaces
      anodically oxidized in chloride solutions.
AB  - Photo-functionalized radical reactions on TiO(2) have been correlated with
      adsorption of organic impurities and decreasing hydrophilicity of titanium-based
      biomaterials. Such reactive oxygen species (ROS) spontaneously generated on
      oxidized titanium surfaces may also have important roles against time-dependent
      degradation of biological ability and adherent micro-organisms. This study
      examined in vitro biological ability as a function of time and antimicrobial
      activity on oxidized titanium surfaces without photo-functionalization.
      Mechanically polished titanium and thermally oxidized titanium surfaces that had
      been stored for 4 wks showed adsorbed organic impurities with decreased surface
      hydrophilicity. Even after the storage period, anodically oxidized titanium
      surfaces enabled super-hydrophilicity without adsorption of organic impurities,
      because of the ROS and the hydrophilic functional groups generated on the
      surfaces. The osteogenic gene expressions of osteoblasts cultured on anodically
      oxidized titanium surfaces with or without storage were significantly higher than
      those on thermally oxidized titanium and polished titanium surfaces. Titanium
      surfaces anodically oxidized in a solution with chloride achieved antimicrobial
      activity against an oral microorganism due to the amount of ROS generated on the
      surface. Thus, titanium anodically oxidized in solution with chloride may have
      potential use for titanium-based internal fixation devices.

PMID- 20810163
TI  - In vitro hemocompatibility of thin film nitinol in stenotic flow conditions.
AB  - Because of its low profile and biologically inert behavior, thin film nitinol
      (TFN) is ideally suited for use in construction of endovascular devices. We have
      developed a surface treatment for TFN designed to minimize platelet adhesion by
      creating a superhydrophilic surface. The hemocompatibility of expanded
      polytetrafluorethylene (ePTFE), untreated thin film nitinol (UTFN), and a surface
      treated superhydrophilic thin film nitinol (STFN) was compared using an in vitro
      circulation model with whole blood under flow conditions simulating a moderate
      arterial stenosis. Scanning electron microscopy analysis showed increased
      thrombus on ePTFE as compared to UTFN or STFN. Total blood product deposition was
      6.3 +/- 0.8 mg/cm(2) for ePTFE, 4.5 +/- 2.3 mg/cm(2) for UTFN, and 2.9 +/- 0.4
      mg/cm(2) for STFN (n = 12, p < 0.01). ELISA assay for fibrin showed 326 +/- 42
      MUg/cm(2) for ePTFE, 45.6 +/- 7.4 MUg/cm(2) for UTFN, and 194 +/- 25 MUg/cm(2)
      for STFN (n = 12, p < 0.01). Platelet deposition measured by fluorescent
      intensity was 79,000 20,000 AU/mm(2) for ePTFE, 810 +/- 190 AU/mm(2) for UTFN,
      and 1600 +/- 25 AU/mm(2) for STFN (n = 10, p < 0.01). Mass spectrometry
      demonstrated a larger number of proteins on ePTFE as compared to either thin
      film. UTFN and STFN appear to attract significantly less thrombus than ePTFE.
      Given TFN's low profile and our previously demonstrated ability to place TFN
      covered stents in vivo, it is an excellent candidate for use in next-generation
      endovascular stents grafts.

PMID- 20810164
TI  - Pathological analysis of umbilical cord ulceration associated with fetal duodenal
      and jejunal atresia.
AB  - Umbilical cord ulceration is a serious complication of fetal intestinal atresia.
      To elucidate the relationship between fetal intestinal atresia and umbilical cord
      ulceration grade, we pathologically examined umbilical cords in 15 duodenal and 5
      jejunal atresia cases and 28 control cases. Microscopic examination of the
      umbilical cords of patients with intestinal atresia revealed high-grade
      ulceration and a significant increase in macrophage numbers (P = 0.0087).
      Transudation of red blood cells was not associated with any specific clinical
      diagnosis, but was seen in all high-grade ulceration cases. It is suggested that
      clinical symptoms become apparent following gradual pathological changes.

PMID- 20810165
TI  - Soil and vegetables enrichment with heavy metals from geological sources in
      Gilgit, northern Pakistan.
AB  - This study was conducted to investigate the concentrations of heavy metals in
      soil and vegetables, and human health risks through ingestion of contaminated
      vegetables. Soil and vegetable samples were collected from different locations in
      Gilgit, northern Pakistan, and analyzed for Cd, Cu, Ni, Pb and Zn. Plant transfer
      factors (PTF), daily intake of metals (DIM) and health risk index (HRI) were also
      calculated. The concentrations of Cd, Cu and Zn exceeded their respective
      permissible limits in soil samples. The highest concentrations of Cu, Ni, Pb and
      Zn were observed in the edible parts of Malva neglecta, Brassica oleracea, Mintha
      sylvestris and Brassica campestris, respectively. PTF values were lower for all
      the selected heavy metals, except for Cd. Furthermore, the HRI values were within
      the safe limit (<1) except for Pb; therefore, the health risks of metals through
      ingestion of vegetables were of great concern in the study area.

PMID- 20810166
TI  - Investigation of the estrogenic risk to feral male brown trout (Salmo trutta) in
      the Shannon International River Basin District of Ireland.
AB  - The estrogenic potential of sewage treatment effluents and their receiving waters
      in the Shannon International River Basin District (SIRBD) of Ireland was
      investigated. An integrated approach, combining biological and chemical methods,
      was conducted to assess 11 rivers adjacent to sewage treatment plants (STPs) and
      their possible interference with the endocrine system of feral brown trout (Salmo
      trutta). Hepatosomatic index, gonadosomatic index, condition factor, histological
      (intersexuality) and endocrine (vitellogenin induction) parameters were assessed
      in a sample size of 10 at each location. The estrogenic burden was determined
      using an in vitro recombinant yeast assay containing the human estrogen receptor
      (YES assay). In addition, endocrine disrupting chemicals (EDCs) were
      quantitatively identified through a selection of pre-concentration techniques
      combined with chromatographic analysis at or near the selected locations.
      Chemical analysis of representative site samples identified phthalates and an
      alkylphenol in water and sediments in MUg/L and mg/kg concentrations,
      respectively. There were no significant difference in somatic indices or the
      condition factor between upstream control and downstream test sites, and there
      was no evidence of reproductive alterations or the presence of intersex in
      studied male brown trout. However, raised vitellogenin (vtg) levels were detected
      in the blood plasma samples of male brown trout at 8 of the 11 sites. Significant
      levels were reported at 3 of the positive sites (p <= 0.05). In one particular
      location, vtg induction was observed in 100% of the male brown trout sampled
      downstream. These findings were supported by the YES assay, where estrogenic
      activity was detected in the same upstream and downstream sites giving 17beta
      estradiol equivalency factor (EEF) values of up to 2.67 ng/L. This study
      represents an integrated assessment approach, confirming the presence of
      estrogens in rivers of the SIRBD of Ireland, thus suggesting a cause-effect
      relationship to prolonged EDC-exposure in fish.

PMID- 20810167
TI  - Health risks associated with consumption of microcystin-contaminated fish and
      shellfish in three Chinese lakes: significance for freshwater aquacultures.
AB  - The risks associated with consuming aquatic products were systematically
      evaluated by analyzing 26 economically important fish and shellfish species which
      were harvested monthly from three large lakes in China during the fisheries catch
      season. Results indicate most of the aquatic products from the three large lakes
      seem to be unsafe for human consumption due to microcystin accumulations, with
      the estimated daily intake (EDI) values 5-148 times, 2-50 times and 1.5-4 times
      higher than the tolerable daily intake (TDI) value in Taihu, Chaohu and Dianchi,
      respectively. In addition, the toxin accumulation in the harvested organisms
      varied intensity from month to month and by species which suggests that
      consumption risks may be reduced or avoided by either adjusting the legal fishing
      seasons or the species of fish and shellfish harvested. This study will provide
      new information about the risks associated with the consumption of aquatic
      products and suggests possible management strategies to reduce or avoid potential
      health risks.

PMID- 20810169
TI  - Perfluoroalkyl compounds in dust from Asian, Australian, European, and North
      American homes and UK cars, classrooms, and offices.
AB  - Perfluoroalkyl compounds (PFCs) were measured in dust from Australian, Canadian,
      French, German, Kazahkstani, Thai, UK, and US homes, and UK cars, classrooms, and
      offices. Most PFCs were significantly lower in Kazahkstan and Thailand than
      elsewhere; 2-(N-methylperfluoro-1-octanesulfonamido)-ethanol (MeFOSE) and 2-(N
      ethylperfluoro-1-octanesulfonamido)-ethanol (EtFOSE) were significantly lower in
      Canada than in the UK and the US; perfluoro-1-hexanesulfonate (PFHxS) was
      significantly lower in Canada than in the UK, and N-ethylperfluoro-1
      octanesulfonamide (EtFOSA) was significantly higher in Australia than in the UK.
      High EtFOSA concentrations in some samples may be consistent with its use as an
      insecticide. Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA),
      PFHxS, and MeFOSE were significantly higher in classrooms than in cars, homes,
      and offices; N-methylperfluoro-1-octanesulfonamide (MeFOSA) was significantly
      lower in classrooms than in homes and offices, and perfluoro-1-octanesulfonamide
      (FOSA) was significantly lower in classrooms than in cars, homes, and offices.
      While homes are usually the most important vector of dust exposure (typically >
      60%), offices and classrooms make important contributions. While diet is usually
      the main exposure pathway for UK adults and children (~1-6 years) for PFOS, PFOA,
      and PFHxS; dust ingestion can be significant under high dust ingestion scenarios.
      Even under high-end exposure scenarios for dust and diet, PFOS and PFOA exposures
      are well within the European Food Safety Authority tolerable daily intakes.

PMID- 20810168
TI  - Cost-effectiveness of targeted versus tailored interventions to promote
      mammography screening among women military veterans in the United States.
AB  - OBJECTIVE: We conducted an economic evaluation of mammography promotion
      interventions in a population-based, nationally representative sample of 5500
      women veterans. METHODS: Women 52 years and older were randomly selected from the
      National Registry of Women Veterans and randomly assigned to a survey-only
      control group and two intervention groups that varied in the extent of
      personalization (tailored vs. targeted). Effectiveness measures were the
      prevalence of at least one self-reported post-intervention mammogram and two post
      intervention mammograms 6-15 months apart. Incremental cost-effectiveness ratios
      (ICERs) were the incremental cost per additional person screened. Uncertainty was
      examined with sensitivity analysis and bootstrap simulation. RESULTS: The
      targeted intervention cost $25 per person compared to $52 per person for the
      tailored intervention. About 27% of the cost was incurred in identifying and
      recruiting the eligible population. The percent of women reporting at least one
      mammogram were .447 in the control group, .469 in the targeted group, and .460 in
      the tailored group. The ICER was $1116 comparing the targeted group to the
      control group (95% confidence interval (CI)=$493 to dominated). The tailored
      intervention was dominated (more costly and less effective) by the targeted
      intervention. CONCLUSION: Decision-makers should consider effectiveness evidence
      and the full recruitment and patient time costs associated with the
      implementation of screening interventions when making investments in mammography
      screening promotion programs. Identification and recruitment of eligible
      participants add substantial costs to outreach screening promotion interventions.
      Tailoring adds substantial cost to the targeted mammography promotion strategy
      without a commensurate increase in effectiveness. Although cost-effectiveness has
      been reported to be higher for some in-reach screening promotion interventions, a
      recent meta-analysis revealed significant heterogeneity in the effect sizes of
      published health-plan based intervention studies for repeat mammography (i.e.,
      some studies reported null effects compared with control groups).

PMID- 20810170
TI  - The autoimmune TCR-Ob.2F3 can bind to MBP85-99/HLA-DR2 having an unconventional
      mode as in TCR-Ob.1A12.
AB  - The generation of T cell receptor (TCR) sequence diversity can produce
      'forbidden' clones able to recognize self-antigens. Here, the structure of the
      complex between a myelin basic protein peptide (MBP85-99), human leukocyte
      antigen (HLA)-DR2 (DRB1*1501/DRA) and TCR-Ob.2F3, the dominant autoimmune clone
      obtained from a multiple sclerosis (MS) patient, has been determined using
      structural docking simulation and dynamics in silico and compared to the
      structure of TCR-Ob.1A12 complexes with the same MHC/peptide determined by X-ray
      crystallography. The two TCRs differ by three amino acids in the CDR3 alpha and
      beta loops. As the result different hydrogen bonds are formed between the two
      CDR3beta loops and the peptide in the complexes of the simulated structures, with
      three hydrogen bonds seen in the TCR-Ob.2F3 complex and five in the TCR-Ob.1A12
      complex. The two TCRs, each located near the N-terminal end of the HLA-DR2
      binding groove and both had an orthogonal binding axis but they deviated by about
      10 degrees . Simulation methods, such as structural docking and molecular
      dynamics as used here, provide an avenue to understand molecular binding mode
      efficiently and more rapidly than obtaining multiple crystal structures when a
      large structural database is already available.

PMID- 20810171
TI  - Corneal sensation and subbasal nerve alterations in patients with herpes simplex
      keratitis: an in vivo confocal microscopy study.
AB  - PURPOSE: To study and correlate corneal sensation in patients with herpes simplex
      keratitis (HSK) with density and morphologic features of subbasal corneal nerves
      by in vivo confocal microscopy (IVCM). DESIGN: Prospective, cross-sectional,
      controlled, single-center study. PARTICIPANTS: Thirty-one eyes with the diagnosis
      of acute (n = 7) or chronic (n = 24) HSK and their contralateral clinically
      unaffected eyes were studied and compared with normal controls (n = 15). METHODS:
      In vivo confocal microscopy (Confoscan 4; Nidek Technologies, Gamagori, Japan)
      and corneal esthesiometry (Cochet-Bonnet; Luneau Ophthalmlogie, Chartres, France)
      of the central cornea were performed bilaterally in all patients and controls.
      Patients were grouped into normal (> 5.5 cm), mild (> 2.5-5.5 cm), and severe (<=
      2.5 cm) loss of sensation. MAIN OUTCOME MEASURES: Changes in corneal nerve
      density, total nerve number, main nerve trunks, branching, and tortuosity were
      evaluated after IVCM and were correlated to corneal sensation, disease duration,
      and number of recurrences. RESULTS: Herpes simplex keratitis eyes, as compared
      with controls, demonstrated significant (P < 0.001) decrease in mean nerve
      density (448.9 +/- 409.3 vs. 2258.4 +/- 989.0 MUm/frame), total nerve number (5.2
      +/- 4.5 vs. 13.1 +/- 3.8), main nerve trunks (2.3 +/- 1.6 vs. 4.7 +/- 1.2), and
      nerve branches (3.2 +/- 4.3 vs. 9.8 +/- 3.3). In contralateral unaffected eyes,
      mean nerve density (992.7 +/- 465.0 MUm/frame), total nerve number (7.8 +/- 3.3),
      and branches (4.5 +/- 2.3) were decreased significantly as compared with controls
      (P < 0.002). Reduced nerve density, total nerve count, and main trunks in HSK
      eyes were correlated significantly with corneal sensation across all subgroups (P
      < 0.001). Nerve density decreased within days of infection and was correlated to
      frequency of episodes in patients with HSK (P < 0.02). CONCLUSIONS: In vivo
      confocal microscopy revealed that the loss of corneal sensation in HSK correlates
      strongly with profound diminishment of the subbasal nerve plexus after herpes
      simplex virus infection. Surprisingly, the contralateral, clinically unaffected
      eyes also demonstrated a diminishment of the subbasal nerve plexus as compared
      with normal subjects, revealing bilateral nerve alteration in an apparently
      unilateral disease.

PMID- 20810172
TI  - Aerobic and anaerobic bacteriology of chronic adenoid disease in children.
AB  - Bacterial cultures from nasopharyngeal swabs of children after adenoidectomy and
      from the removed adenoid tissue in the same patient group were compared. At the
      same time, the colony-forming unit, as a measure of viable bacterial cells and
      the composition of isolated bacteria were also determined in the case of adenoid
      tissue. Our findings showed that the culture results of nasopharyngeal swabs and
      inner part of the adenoid tissue are in close correlation. Polymicrobial aerobic
      anaerobic flora was present in all instances. The predominant aerobic isolates in
      all two groups were S. pneumoniae, H. influenzae and M. catarrhalis. Anaerobic
      bacteria most commonly recovered in the adenoid were Peptostreptococcus spp.,
      Prevotella spp., and Fusobacterium spp.

PMID- 20810173
TI  - Cause-effect relationships in medicine: a protein network perspective.
AB  - Current target-based drug discovery platforms are not able to predict drug
      efficacy and the full spectrum of drug effects in organisms. Hence, many
      experimental drugs do not survive the lengthy and costly process of drug
      development. Understanding how drugs affect cellular network structures and how
      the resulting signals are translated into drug effects is extremely important for
      the discovery of new medicines. This requires a greater understanding of cause
      effect relationships at the organism, organ, tissue, cellular, and molecular
      level. There is a growing recognition that this information must be integrated
      into discovery paradigms, but a 'road map' for obtaining and integrating
      information about heterogeneous networks into drug-discovery platforms currently
      does not exist. This review explores recent network-centered approaches developed
      to investigate the genesis of medicine and disease effects, specifically
      highlighting protein-protein interaction network models and their use in cause
      effect analyses in medicine.

PMID- 20810174
TI  - The effects of the alkyl polycyclic aromatic hydrocarbon retene on rainbow trout
      (Oncorhynchus mykiss) immune response.
AB  - The objective of this study was to examine the immune toxicity of the alkyl
      polycyclic aromatic hydrocarbon (PAH) retene (7-isopropyl-1-methyl phenanthrene)
      in rainbow trout. Retene is a common alkyl PAH associated with combustion of
      terrestrial plants or industrial effluents. Rainbow trout were injected
      intraperitoneally with a single dose of 0, 1, or 10mg/kg of retene and sampled at
      21d. Within each retene treatment, co-injection of formalin-killed Aeromonas
      salmonicida or a phosphate buffered saline sham was used to stimulate the trout
      immune system. At the highest retene dose (10mg/kg) there was an increase in
      total blood leukocyte counts but only in the A. salmonicida-injected group. This
      result was paralleled by an increase in leukocytes in differential blood cell
      counts. There was an overall increase in A. salmonicida-specific antibody titre
      due to the antigen injection and there was also a significant stimulation of
      antibody production response at the 10mg/kg retene dose. At the tissue level,
      immunohistochemistry revealed a greater density of B-lymphocytes at the highest
      retene dose in spleen and head kidney. A number of immune specific transcripts
      including the Th2 marker CD4, TCR, MHCII TNFalpha, and the Th1 marker CD8,
      INFgamma were examined by quantitative RT-PCR in spleen and head kidney. There
      was no influence of the A. salmonicida antigen on the expression of Th1 related
      genes in either tissue but increased production of Th2 related CD4 co-receptor
      transcripts was observed in spleen at both retene concentrations. Retene appeared
      to be mildly immunostimulatory, either on its own, or in combination with an
      inactivated A. salmonicida immune challenge and these data suggest that exposures
      of fishes to retene may not pose significant risk of eliciting immunotoxic
      effects.

PMID- 20810175
TI  - 2,4,6-Trichlorophenol mediated increases in extracellular peroxidase activity in
      three species of Lemnaceae.
AB  - Chlorinated phenols, or chlorophenols, are persistent priority pollutants that
      are widespread in the environment. Class III peroxidases are well-characterised
      plant enzymes that can catalyse the oxidative dechlorination of chlorophenols.
      Expression of these enzymes by plants is commonly associated with plant stress,
      therefore limiting scope for phytoremediation. In this study, we have
      quantitatively compared peroxidase activity and phytotoxicity as a function of
      2,4,6-trichlorophenol (TCP) concentration in three species of Lemnaceae; Lemna
      minor, Lemna gibba and Landoltia punctata. Effects of TCP on the growth rates of
      the three species differed considerably with L. punctata being the most tolerant
      species. TCP also affected photosynthetic parameters, causing a decrease in open
      photosystem II reaction centres (qP) and, in L. punctata only, a decrease in non
      photochemical quenching (qN). In parallel, TCP exposure resulted in increased
      peroxidase activity in all three species. Peroxidase activity in L. minor and L.
      gibba displayed an inverse relationship with biomass accumulation, i.e. the more
      growth reduction the more peroxidase activity. In contrast, induction of
      peroxidase activity in L. punctata was bi-phasic, with a TCP-induced activity
      peak at concentrations that had no major effect on growth, and further induction
      under phytotoxic concentrations. The mechanism by which L. punctata recognises
      and responds to low concentrations of an anthropogenic compound, in the absence
      of wide-ranging stress, remains enigmatic. However, we conclude that this
      "window" of peroxidase production in the absence of major growth inhibition
      offers potential for the development of sustainable, peroxidise-mediated
      phytoremediation systems.

PMID- 20810176
TI  - Changes in non-specific biomarkers in the Mediterranean barbel (Barbus
      meridionalis) exposed to sewage effluents in a Mediterranean stream (Catalonia,
      NE Spain).
AB  - The effluents from sewage treatment plants strongly influence the water quality
      and flow of Mediterranean streams. These effluents play a crucial role in
      maintaining the aquatic communities of these ecosystems, particularly in the
      absence of natural flow resulting from climate constraints or intensive water
      use. To detect the ecological effects of these effluents, we used non-lethal
      biomarkers in Barbus meridionalis and traditional assessment protocols in the
      Ripoll River (NE of Spain). Our results demonstrate the utility of haematological
      parameters. In comparison with fish at reference sites, we detected a decrease in
      haematocrit and haemoglobin, neutrophilia, lymphopenia, monocytosis, a rise in
      the nucleo-cytoplasmatic ratio of erythrocytes and an increase in the frequency
      of abnormal, immature and senescent erythrocytes. Many haematological parameters
      correlated significantly with the environmental parameters measured. In addition
      to these haematological alterations, histopathological examination also revealed
      damage in fish livers but no impact was detected by the regional index of biotic
      integrity using fish as bioindicators. To the best of our knowledge, this study
      is the first to report this battery of haematological parameters as biomarkers on
      a freshwater fish in a Mediterranean stream. In a region in which more than 50%
      of native fish species are classified as endangered or vulnerable, there is an
      urgent need to find biomarkers that do not harm the animals.

PMID- 20810177
TI  - Reactions to caregiving in frailty research.
AB  - Frailty is a syndrome characterized by decreased functional ability and
      associated with institutionalization. Many community-living frail older people
      rely upon the support of a family member or friend. However, there is a paucity
      of research exploring the reactions to caring for older people empirically
      identified as frail. The objective of this study was to describe carers of
      community-living older people identified as frail, using accepted criteria,
      identify care characteristics and ascertain relationships that contribute to
      reactions to caregiving. A cross-section of carers of community-living frail
      people (>= 70 years) completed a postal questionnaire; the Caregiver Reaction
      Assessment (CRA) evaluated reactions to caregiving. Ninety-three carers completed
      the questionnaire (68% response rate). Correlation and multivariate analysis of
      variance tests (MANOVA) demonstrated statistically significant relationships
      between several care characteristics and reactions to caregiving. Carers who
      provide more than 20 h of care per week and report a low self-perceived health
      status are susceptible to significant health and financial problems and
      disruption to their daily schedule. Two strategies for improving reactions to
      caring for persons with frailty are proposed: financial support that assists
      carers to improve their health status and the provision of regular formal
      assistance, rather than intermittent respite care.

PMID- 20810178
TI  - Trajectories of depression and their relationship with health status and social
      service use.
AB  - This longitudinal study was conducted between 1994 and 2004 in a cohort of
      Southern Taiwan community-living elderly residents. The study aims to explore the
      trajectories of depression and how these patterns differed between respondents
      who survived and those who died during data collection phases; this study also
      investigated how health status change and health/social service use predicted the
      different trajectories of depression. Eight hundred and ten participants had
      completed all six waves of the survey or were followed-up at each wave until
      death in the prospective study in Kaohsiung City. Depressive symptoms were
      evaluated by the Short Psychiatric Evaluation Schedule (SPES). Changes in levels
      of depression during the ageing process were identified. Different trajectories
      clearly reflected heterogeneity within depression and the association with
      mortality. The study highlighted that diabetes, gastrointestinal problems, heart
      disease and disability, whether at baseline or as new occurrences, were
      predictors of health decline. High uses of health/social services were also
      predictive of increased depression. These findings identified depression as a
      highly dynamic process, characterized by different trajectories of depression
      between states of no, mild and severe depression. Greater awareness of these
      various trajectories should potentially improve the prevention and/or management
      strategies of depression.

PMID- 20810179
TI  - The impact of casinos on fatal alcohol-related traffic accidents in the United
      States.
AB  - Casinos have been introduced throughout the U.S. to spur economic development and
      generate tax revenues. Yet, casinos may also be associated with a variety of
      social ills. One issue that has not been empirically tested in the literature is
      whether there is a link between casino expansion and alcohol-related fatal
      traffic accidents. We suspect a link may exist since casinos often serve alcohol
      to their patrons and, by their dispersed nature, could impact driving distances
      after drinking. Using the variation in the timing and location of casino openings
      over a 10-year period, we isolate the impact of casino introduction on alcohol
      related fatal accidents. Results indicate that there is a strong link between the
      presence of a casino in a county and the number of alcohol-related fatal traffic
      accidents. However, this relationship is negatively related to the local-area
      (county) population. Results prove durable, as we subject them to robustness
      checks.

PMID- 20810180
TI  - Neuroimaging-based approaches in the brain-computer interface.
AB  - Techniques to enable direct communication between the brain and
      computers/machines, such as the brain-computer interface (BCI) or the brain
      machine interface (BMI), are gaining momentum in the neuroscientific realm, with
      potential applications ranging from medicine to general consumer electronics.
      Noninvasive BCI techniques based on neuroimaging modalities are reviewed in terms
      of their methodological approaches as well as their similarities and differences.
      Trends in automated data interpretation through machine learning algorithms are
      also introduced. Applications of functional neuromodulation techniques to BCI
      systems would allow for bidirectional communication between the brain and the
      computer. Such bidirectional interfaces can relay information directly from one
      brain to another using a computer as a medium, ultimately leading to the concept
      of a brain-to-brain interface (BBI).

PMID- 20810181
TI  - Bacteriophages as potential new therapeutics to replace or supplement
      antibiotics.
AB  - Over recent decades, a growing body of literature has validated the use of
      bacteriophages for therapy and prophylaxis in the war against drug-resistant
      bacteria. Today, much more is known about bacteriophages than in the 1930s when
      phage therapy first appeared and began to spread to many countries. With rapid
      dissemination of multi-drug-resistant bacterial pathogens, the interest in
      alternative remedies to antibiotics, including bacteriophage treatments, is
      gaining new ground. Based on recent experience and current results of
      bacteriophage applications against bacterial infections in countries where this
      alternative therapy is approved, many scientists and companies have come to
      believe that the use of phages for treating and preventing bacterial diseases
      will be successful.

PMID- 20810182
TI  - Survival of a Lactococcus lactis strain varies with its carbohydrate preference
      under in vitro conditions simulated gastrointestinal tract.
AB  - Lactococcus lactis G50 is a candidate probiotic bacterium with immunomodulatory
      activity. We evaluated the suitability of strain G50 as orally administered
      probiotics on the basis of its resistance to simulated gastrointestinal (GI)
      stress, including the presence of lysozyme, low pH, and bile, carbohydrate
      preference, and bacterial cell surface composition in vitro. This strain survived
      GI stresses but its resistance to lysozyme was affected by the type of available
      carbohydrate in the growth medium; it was unaffected with lactose, xylose and
      galactose as the carbon source but was significantly lower for fructose, sucrose
      and glucose. The resistance of strain G50 to low pH was unaffected by carbon
      source. Resistance to bile was determined by two methods; growth and survival
      study and varied with carbon source. The growth of strain G50 with 0.3% bile was
      lowest in lactose-containing broth, higher in broth containing xylose or
      galactose, and highest in broth containing sucrose, glucose, or fructose. In
      contrast, the survival of cells after 3h incubation with 0.3% bile was highest
      for lactose. The hydrophobicity of bacterial cells, which can be related to
      epithelial adhesion in certain cases, was also highest for lactose. The fatty
      acid composition of cells grown on lactose differed from that of cells grown on
      other carbon sources. These results suggest that survival of strain G50 in the GI
      tract depends on the kinds of carbohydrates available. Carbohydrate preferences
      were observed for other strains of lactic acid bacteria under conditions of GI
      stress, and this preference varied with the strain and the type of GI stress.
      Careful consideration should be given to the selection of carbohydrates for in
      vitro testing of the survival of lactic acid bacteria in the GI tract.

PMID- 20810183
TI  - Diabetes and sleep: a complex cause-and-effect relationship.
AB  - Strong associations of diabetes with sleep impairment have been frequently
      reported. In the present review, we discuss current evidence and hypotheses for
      how type 1 and type 2 diabetes mellitus are associated with sleep impairment.
      This association may be described as a vicious circle, where sleep disorders
      favor the development of type 2 diabetes or exacerbate the metabolic control of
      both types of diabetes, whereas diabetes itself, especially when associated with
      poor metabolic control, is often followed by sleep disorders. In this review,
      novel findings concerning the neuro-endocrine-metabolic mediation of the
      mentioned circle are highlighted. Understanding how this association occurs, the
      impact of sleep impairment on diabetes, and the impact of diabetes on the
      development or exacerbation of sleep disorders should lead to potential new
      therapeutic strategies for treating both conditions.

PMID- 20810184
TI  - Oral N-acetylcysteine rescues lethality of hepatocyte-specific Gclc-knockout
      mice, providing a model for hepatic cirrhosis.
AB  - BACKGROUND & AIMS: Certain liver diseases have been associated with depletion of
      glutathione (GSH), the major antioxidant in the liver. A recent report about
      Gclc(h/h) mice with a hepatocyte-specific ablation of Gclc (the gene encoding the
      catalytic subunit of the rate-limiting enzyme in GSH synthesis) has shown an
      essential role of GSH in hepatic function. Gclc(h/h) mice develop severe
      steatosis and die of liver failure within one month, due to ~95% depletion of
      hepatic GSH; mitochondria are the major affected organelles, displaying abnormal
      ultrastructure and impaired functioning. METHODS: Gclc(h/h) mice were fed with L
      N-acetylcysteine (NAC; 10 g/L) in drinking water, starting at postnatal day 18.
      RESULTS: Gclc(h/h) mice were rescued by use of NAC supplementation, and survived
      until adulthood. NAC replenished the mitochondrial GSH pool and attenuated
      mitochondrial damage, with accompanying diminished hepatic steatosis; however,
      abnormal liver biochemical tests, hepatocyte death, and hepatic oxidative stress
      persisted in the rescued mice. At 50 days of age, the liver from rescued
      Gclc(h/h) mice started to display characteristics of fibrosis and at age 120
      days, macronodular cirrhosis was observed. Immunohistostaining for liver-specific
      markers as well as the expression profile of hepatic cytokines indicated that the
      repopulation of hepatocytes in the cirrhotic nodules involved the expansion of
      oval cells. CONCLUSIONS: Replenishment of mitochondrial GSH and restoration of
      mitochondrial function by NAC prevents mortality caused by the loss of hepatocyte
      GSH de novo synthesis, allowing steatosis to progress to a chronic stage. Thus,
      with NAC supplementation, Gclc(h/h) mice provide a model for the development of
      liver fibrosis and cirrhosis.

PMID- 20810185
TI  - Autophagy in liver diseases.
AB  - Autophagy, or cellular self-digestion, is a cellular pathway crucial for
      development, differentiation, survival, and homeostasis. Its implication in human
      diseases has been highlighted during the last decade. Recent data show that
      autophagy is involved in major fields of hepatology. In liver ischemia
      reperfusion injury, autophagy mainly has a prosurvival activity allowing the cell
      for coping with nutrient starvation and anoxia. During hepatitis B or C
      infection, autophagy is also increased but subverted by viruses for their own
      benefit. In hepatocellular carcinoma, the autophagy level is decreased. In this
      context, autophagy has an anti-tumor role and therapeutic strategies increasing
      autophagy, as rapamycin, have a beneficial effect in patients. Moreover, in
      hepatocellular carcinoma, Beclin-1 level, an autophagy protein, has a prognostic
      significance. In alpha-1-antitrypsin deficiency, the aggregation-prone ATZ
      protein accumulates in the endoplasmic reticulum. This activates the autophagic
      response which aims at degrading mutant ATZ. Some FDA-approved drugs which
      enhance autophagy and the disposal of aggregation-prone proteins may be useful in
      alpha-1-antitrypsin deficiency. Following alcohol consumption, autophagy is
      decreased in liver cells, likely due to a decrease in intracellular 5'-AMP
      activated protein kinase (AMPk) and due to an alteration in vesicle transport in
      hepatocytes. This decrease in autophagy contributes to the formation of Mallory
      Denk bodies and to liver cell death. Hepatic autophagy is defective in the liver
      in obesity and its upregulation improves insulin sensitivity.

PMID- 20810186
TI  - Central nervous system dysfunction in primary biliary cirrhosis and its
      relationship to symptoms.
AB  - BACKGROUND & AIMS: Primary biliary cirrhosis (PBC) is associated with fatigue,
      memory impairment, and sleep disturbances. These symptoms suggest the possibility
      of underlying central nervous system (CNS) dysfunction. During exercise, fatigue
      develops due to muscular processes (peripheral fatigue) and decreased
      neurological activation of the muscle (central fatigue). In this study we
      objectively quantify central and peripheral fatigue in PBC and investigate the
      integrity of cortical inhibitory and excitatory circuits. Finally, we determine
      the relationship of these indices to the symptoms of PBC. METHODS: 16 early-stage
      PBC patients, 8 post-liver transplant PBC patients, and 12 age-matched controls
      were studied at the Specialist PBC clinic and neuroscience research unit. In
      these patients, twitch interpolation was used to measure peripheral and central
      fatigue. Paired-pulse trans-cranial magnetic stimulation was used to assess intra
      cortical inhibition (ICI) and facilitation (ICF). RESULTS: PBC patients had a
      significantly lower central activation before fatiguing exercise (mean 86.6.8%
      (+/-12.75) vs. 95.2% (+/-7.4); p<0.05) and a greater response variability than
      controls. The decline in central activation during exercise and peripheral
      fatigue were normal. ICI was significantly reduced in PBC patients and daytime
      somnolence was greater in patients where net inhibition exceeded facilitation.
      Transplanted and non-transplanted patients had similar central activation, ICI,
      and ICF. CONCLUSIONS: PBC patients have impaired central activation and abnormal
      ICI, suggesting CNS abnormalities beyond voluntary control. Transplanted and non
      transplanted patients show similar abnormalities raising interesting questions
      about the mechanisms underpinning these changes and the permanence of
      neurological dysfunction in PBC. ICI and ICF and the balance between them are
      related to daytime somnolence (an important symptom in PBC).

PMID- 20810187
TI  - The role of supplemental coverage in a universal health insurance system: Some
      Canadian evidence.
AB  - OBJECTIVE: To examine the effect of supplemental health insurance for
      prescription drug coverage on health care utilization as measured by the number
      of visits to physicians in a setting with incomplete public insurance coverage.
      METHODS: A latent-class modeling approach is used to capture the presence of
      latent heterogeneity in the utilization of physician services. The insurance
      variable is grouped into three different types, depending upon how it is provided
      - by government, employers, or private companies. The data for this study come
      from the Ontario component of the Canadian Community Health Survey 2005, a
      representative sample of the Ontario population, conducted by Statistics Canada.
      RESULTS: We find that physician health care utilization responds to the presence
      and type of insurance, and that the results vary substantially across different
      types of individuals based on unobservable health status characterized by two
      latent classes: low users (healthy) and high users (less healthy). CONCLUSIONS:
      The fact that not all individuals have access to supplemental insurance for
      prescription drug coverage calls into question the universality of public
      insurance that does not cover important complementary services, such as
      outpatient prescription drugs.

PMID- 20810188
TI  - Stochastic models of population extinction.
AB  - Theoretical ecologists have long sought to understand how the persistence of
      populations depends on biotic and abiotic factors. Classical work showed that
      demographic stochasticity causes the mean time to extinction to increase
      exponentially with population size, whereas variation in environmental conditions
      can lead to a power-law scaling. Recent work has focused especially on the
      influence of the autocorrelation structure ('color') of environmental noise. In
      theoretical physics, there is a burst of research activity in analyzing large
      fluctuations in stochastic population dynamics. This research provides powerful
      tools for determining extinction times and characterizing the pathway to
      extinction. It yields, therefore, sharp insights into extinction processes and
      has great potential for further applications in theoretical biology.

PMID- 20810189
TI  - Increasing sucrose concentrations promote phenylpropanoid biosynthesis in
      grapevine cell cultures.
AB  - Vitis vinifera cell suspensions are a suitable model system to study the
      metabolic regulation of a large range of high valuable polyphenols that are
      important in understanding the physiology of the plant and for nutraceutical,
      pharmaceutical and medical purposes. Increasing sucrose concentrations were found
      to promote cell growth and phenylpropanoid biosynthesis in grape cell cultures
      obtained from cv. Barbera immature berries. This led to an intracellular
      accumulation and/or release into the media of specific polyphenol families (in
      particular, anthocyanins, catechins and stilbenes). This effect was partially
      correlated with a sucrose modulation of the transcription of some key
      biosynthetic enzymes, such as phenylalanine ammonia lyase, chalcone synthase,
      chalcone-flavanone isomerase and stilbene synthase. Total catechin amounts, both
      endogenous and released in the media, were increased in proportion to the sugar
      concentration, as were anthocyanin and stilbene production. Sugar treatment
      notably improved the endogenous accumulation and release in the culture media of
      resveratroloside, a resveratrol mono-glycoside, which is the most abundant
      stilbene found in grape cultures, especially in cv. Barbera. We hypothesize that
      high sucrose concentrations (exceeding those naturally-occurring in ripe berries)
      could play a role in plant defense via the induction of secondary metabolites,
      such as stilbenes.

PMID- 20810190
TI  - 3D-QSAR analysis of human immunodeficiency virus entry-1 inhibitors by CoMFA and
      CoMSIA.
AB  - 3D-QSAR studies namely CoMFA, CoMFA region focusing and CoMSIA have been carried
      out on a series (36 compounds) of HIV-1 entry inhibitors. An alignment rule for
      the compounds was defined using Distill in SYBYL 7.3. Models were validated using
      a data set obtained by dividing the data set into a training set and test set
      using hierarchical clustering, based on the CoMFA fields and biological
      activities (pIC(50)). The best predictions were obtained with a CoMFA region
      focusing model (q(2) = 0.719, r(pred)(2) = 0.911), CoMFA standard model (q(2) =
      0.660, r(pred)(2) = 0.890), and CoMSIA (steric and hydrophobic) model (q(2) =
      0.521, r(pred)(2) = 0.794). The statistical parameters from the models indicate
      that the data are well fitted and have high predictive ability. Moreover, the
      resulting 3D CoMFA/CoMSIA contour maps provide useful guidance for designing
      highly active inhibitors.

PMID- 20810191
TI  - Aqua mediated synthesis of 2-amino-6-benzothiazol-2-ylsulfanyl-chromenes and its
      in vitro study, explanation of the structure-activity relationships (SARs) as
      antibacterial agent.
AB  - Multi-component reaction (MCR) involves coupling of p-bromophenol with 2
      Benzothiazolethiol, malononitrile and substituted aldehydes in aqueous K(2)CO(3)
      as green base to synthesize 2-amino-6-benzothiazol-2-ylsulfanyl-chromenes. This
      multi-component reaction thus offers a higher yield and versatility in the
      preparation of densely functionalized oxygen heterocycles. The newly synthesized
      compounds were screened for their antibacterial activities against positive and
      gram negative pathogenic strains to bacteria. SAR analysis was performed to
      explore comprehensive structure-activity relationships and a statistically
      reliable model to explain their antibacterial activities.

PMID- 20810192
TI  - Synthesis and evaluation of indole, pyrazole, chromone and pyrimidine based
      conjugates for tumor growth inhibitory activities--development of highly
      efficacious cytotoxic agents.
AB  - Based upon the lead compounds 10 and 11, a number of conjugates were synthesized
      by the combination of chromone-pyrimidine, chromone-indolinone, chromone
      pyrazole, indole-pyrimidine, indole-indolinone and indole-pyrazole moieties.
      Evaluation of these compounds for tumor growth inhibitory activities over 60
      human tumor cell lines provided highly efficacious compounds 15, 41, 43, 66, 69,
      and 72 with an average GI(50) over all the 60 human tumor cell lines as 3.2 MUM,
      3.1 MUM, 1.7 MUM, 2.6 MUM, 50.1 MUM and 2.0 MUM, respectively.

PMID- 20810193
TI  - Synthesis and anticancer activity evaluation of 4-thiazolidinones containing
      benzothiazole moiety.
AB  - Antitumor screening of several novel 4-thiazolidinones with benzothiazole moiety
      has been performed. Reactions of (benzothiazole-2-yl)hydrazine with
      trithiocarbonyl diglycolic acid or 6-methyl-2-aminobenzothiazole with 2
      carbethoxymethylthio-2-thiazoline-4-one have yielded starting 3- (1) or 2
      substituted (11) 4-thiazolidinones which have been subsequently utilized in a
      Knoevenagel condensation for obtaining a series of 5-arylidene derivatives 2-10,
      12-16. Compound 11 has been obtained alternatively by a counter synthesis method
      based on the reaction of 2-chloro-N-(6-methylbenzothiazol-2-yl)-acetamide and
      ammonium thiocyanate. The structures of compounds have been determined by (1)H,
      (13)C NMR, IR and X-ray analysis. In vitro anticancer activity of the synthesized
      compounds was tested by the National Cancer Institute and two (6, 16) of them has
      revealed the anticancer activity on leukemia, melanoma, lung, colon, CNS,
      ovarian, renal, prostate and breast cancers cell lines. Among tested compounds, 2
      {2-[3-(benzothiazol-2-ylamino)-4-oxo-2-thioxothiazolidin-5-ylidenemethyl]-4
      chlorophenoxy}-N-(4-methoxyphenyl)-acetamide (6) was found to be the most active
      candidate with average logGI(50) and logTGI values -5.38 and -4.45 respectively.

PMID- 20810194
TI  - Synthesis of some p-toluenesulfonyl-hydrazinothiazoles and hydrazino-bis
      thiazoles and their anticancer activity.
AB  - A series of novel p-toluenesulfonyl-hydrazinothiazoles and hydrazino-bis
      thiazoles derivatives (2a-f, 3a-f and 5-8) were synthesized by initial
      condensation of p-toluenesulfonylthiosemicarbazide 1 with a series of alpha
      halogenocarbonyls in acetone or dimethylformamide (DMF)/acetone, mixture. All our
      synthesized compounds were submitted for further acylation reaction in the
      presence of acetic anhydride. The structures of newly synthesized derivatives 2a
      f, 3a-f and 5-8 were confirmed by IR, (1)H-NMR, EIMS spectral data and elemental
      analysis. Compounds 2a, 2c, 2d, 2e and 3a showed significant anticancer
      activities (IC(50)<10 MUM) on both prostate DU-145 and hepatocarcinoma Hep-G2
      cancer cell lines.

PMID- 20810195
TI  - Tell me a story--a conceptual exploration of storytelling in healthcare
      education.
AB  - The importance of storytelling as the foundation of human experiences cannot be
      overestimated. The oral traditions focus upon educating and transmitting
      knowledge and skills and also evolved into one of the earliest methods of
      communicating scientific discoveries and developments. A wide ranging search of
      the storytelling, education and health-related literature encompassing the years
      1975-2007 was performed. Evidence from disparate elements of education and
      healthcare were used to inform an exploration of storytelling. This conceptual
      paper explores the principles of storytelling, evaluates the use of storytelling
      techniques in education in general, acknowledges the role of storytelling in
      healthcare delivery, identifies some of the skills learned and benefits derived
      from storytelling, and speculates upon the use of storytelling strategies in
      nurse education. Such stories have, until recently been harvested from the
      experiences of students and of educators, however, there is a growing realization
      that patients and service users are a rich source of healthcare-related stories
      that can affect, change and benefit clinical practice. The use of technology such
      as the Internet discussion boards or digitally-facilitated storytelling has an
      evolving role in ensuring that patient-generated and experiential stories have a
      future within nurse education.

PMID- 20810196
TI  - Do gender differences in mental health contribute to gender differences in
      physical health?
AB  - Previous research has demonstrated that women and men tend to have different
      types of mental and physical health problems. Using data from the US National
      Comorbidity Survey Replication (NCS-R) of 2001-2003, we consider whether the
      female excess in internalizing disorders contributes to the female excess in
      chronic debilitating conditions and whether the male excess in externalizing
      disorders contributes to the male excess in life threatening conditions. We find
      that women have significantly higher odds of meeting the DSM-IV criteria for one
      or more lifetime internalizing disorders and significantly lower odds of meeting
      the DSM-IV criteria for one or more lifetime externalizing disorders. We also
      find that women have higher odds of reporting four of the ten chronic
      debilitating conditions examined, including arthritis, frequent or severe
      headaches, seasonal allergies, and gallbladder removal, and lower odds of
      reporting three of the six life threatening conditions examined, including
      stroke, heart disease, and high blood pressure. We conclude that the female
      excess in internalizing disorders partially mediates, or explains, the female
      excess in arthritis, headaches, and gallbladder removal, while the male excess in
      externalizing disorders partially accounts for the male excess in heart disease
      and high blood pressure.

PMID- 20810197
TI  - Understanding community context and adult health changes in China: development of
      an urbanicity scale.
AB  - The classification of places as either urban or rural is typically based on an
      absolute threshold of population and/or population density. However, conceptual
      definitions of urbanization and urbanicity encompass dimensions beyond solely
      population size and population density. Multiple important distinguishing urban
      characteristics beyond population size have been described. The crude
      classification of places as urban or rural coupled with infrequent updates to
      this information creates a measure that is prone to misclassification error. An
      improved measure of urbanicity would draw information from the domains that
      characterize urban and rural places, would be sensitive to changes over time, and
      would represent gradations on the continuum from rural to urban environments. The
      goal of the current study was to develop such a scale from existing data, test
      whether the scale was reliable and valid, and assess whether it provided
      information beyond what could be determined from the traditional urban/rural
      dichotomous variable. We utilized established scaling procedures from the
      psychometric literature to construct and evaluate a multicomponent scale to
      measure urban features on a continuum in China. We also provided an example of
      its potential contribution to health research by examining its relationship with
      the adult body mass index (BMI). Because the scale was constructed and tested
      using established scaling procedures and using a wide array of variables, it
      represents an improvement over previous attempts at such a scale and will provide
      a reliable and valid measurement tool for researchers in this arena. We
      demonstrate that the scale predicts the incidence of overweight/obesity
      populations in China, but it promises to be most useful for other economic,
      demographic, social welfare, and health outcomes.

PMID- 20810199
TI  - Visuomotor binding in older adults.
AB  - Action integration is the process through which actions performed on a stimulus
      and perceptual aspects of the stimulus become bound as a unitary object. This
      process appears to be controlled by the dopaminergic system in the prefrontal
      cortex, an area that is known to decrease in volume and dopamine functioning in
      older adults. Although the decline should lead to reduced action integration in
      older adults, we found equivalent integration in both young and older adults.
      This indicates that older adults may be able to compensate for their dopaminergic
      deficiencies by activating additional neural networks that are not used by young
      adults.

PMID- 20810200
TI  - Chain of Brain Preservation--a concept to facilitate early identification and
      initiation of hypothermia to infants at high risk for brain injury.
AB  - BACKGROUND: Therapeutic hypothermia has been associated with improved outcomes in
      term infants particularly in those who present with moderate hypoxic-ischemic
      encephalopathy (HIE). However, in the three major studies the time to initiate
      cooling was at approximately 4.5 postnatal hours. OBJECTIVE: To determine in term
      infants who meet criteria for therapeutic hypothermia whether specific clinical
      and/or biochemical parameters might identify those high risk infants destined for
      abnormal neurodevelopmental outcome even sooner than is currently possible.
      DESIGN/METHODS: Retrospective chart review for the following parameters:
      gestational age, birth weight, sex, labor complications, mode of delivery, 10 min
      Apgar<=3, cardio-pulmonary resuscitation in the delivery room, cord arterial pH
      and base deficit, initial postnatal pH and base deficit obtained within 1h, aEEG,
      Sarnat staging and seizures at enrollment. Abnormal outcome included death and
      neurodevelopmental deficits. RESULTS: At a single tertiary care center in a
      metropolitan area, 45 term infants with moderate to severe HIE were treated with
      selective head cooling initiated at a mean of 4.69+/-0.79 h of life; 43/45 (96%)
      were outborn. Five (11%) infants died and of survivors 26 (58%) are normal and 14
      (31%) infants are abnormal at follow-up ranging from 12 to 26 months. Infants
      with abnormal vs. normal outcome were of comparable gestational age, birth weight
      with no differences in any parameters between groups except that in infants with
      abnormal vs. normal outcome the postnatal pH obtained within the first postnatal
      hour was lower, i.e. 6.87+/-0.15 vs. 7.00+/-0.22 (p=0.02) and abnormal infants
      were more likely to present with severe encephalopathy, i.e. 15/19 (79%) vs. 6/26
      (23%) (p=0.0002) and clinical seizures, i.e. 14/19 (74%) vs.10/26 (38%) (p=0.03)
      on admission. CONCLUSIONS: High risk infants who become candidates for
      therapeutic hypothermia and ultimately have an abnormal outcome may be identified
      by an additional early postnatal biochemical marker, i.e. the presence of
      profound metabolic acidosis. An earlier induction of hypothermia that currently
      occurs particularly in infants with severe encephalopathy may potentially improve
      outcome. Given that most infants are outborn, a time sensitive education metaphor
      termed Chain of Brain Preservation may facilitate early recognition of high risk
      infants and thus earlier treatment.

PMID- 20810201
TI  - Prediction of peripartum hysterectomy and end organ dysfunction in major
      obstetric haemorrhage.
AB  - OBJECTIVES: The aims of this study are to determine the incidence and aetiology
      of major obstetric haemorrhage (MOH) in our population, to examine the success
      rates of medical and surgical interventions and to identify risk factors for
      peripartum hysterectomy and end organ dysfunction (EOD). STUDY DESIGN: This
      prospective study from 2004 to 2007 was carried out in three Dublin maternity
      hospitals. Women were identified as having MOH if they received >=5 units of red
      cell concentrate (RCC) acutely. Risk factors for hysterectomy or end organ
      dysfunction were calculated using logistic regression. RESULTS: One hundred and
      seventeen cases of MOH in 93,291 deliveries were identified (1.25/1000). The
      predominant cause was uterine atony. Haemostasis was achieved with medical
      therapy alone in 15% of cases. The hydrostatic balloon and the B-Lynch suture
      arrested bleeding in 75% and 40% of cases utilised respectively. Hysterectomy was
      required to arrest bleeding in 24% of women and 16% of women developed end organ
      dysfunction (11 had both). There was one maternal death. Independent risk factors
      for hysterectomy included the number of previous caesarean sections (OR 3.28, 95%
      CI 1.95-5.5), placenta praevia (OR 13.5, 95% CI 7.7-184), placenta accreta (OR
      37.7, 95% CI 7.7-184), uterine rupture (OR 7.25, 95% CI 1.25-42) and the number
      of units of RCC transfused (OR 1.31, 95% CI 1.13-1.5). Independent risk factors
      for end organ dysfunction (EOD) were placenta accreta (OR 5, 95% CI 1.5-16.5),
      uterine rupture (OR 13.86, 95% CI 2.32-82), the number of RCC transfused (OR
      1.31, 95% CI 1.13-1.5) and the minimum haematocrit recorded (OR 5.53, 95% CI 1.7
      18). CONCLUSIONS: MOH is complicated by hysterectomy in 24% and end organ
      dysfunction in 16% of cases. The risk of peripartum hysterectomy is increased
      with the number of previous caesarean sections, the aetiology of the bleed,
      namely placenta praevia/accreta or uterine rupture and the volume of blood
      transfused. Critically, failure to maintain optimal haematocrit during the acute
      event was associated with end organ dysfunction.

PMID- 20810202
TI  - Does levator avulsion increase urethral mobility?
AB  - OBJECTIVE: It is often assumed that stress urinary incontinence may be due to
      abnormal pelvic floor muscle function or anatomy. This may be mediated through
      urethral hypermobility. The aim of the study was to determine the association
      between major levator ani defects ('avulsion') and urethral mobility. STUDY
      DESIGN: Three hundred and five women were referred to a tertiary referral service
      for lower urinary tract and prolapse symptoms between December 2006 and July
      2008. All patients had undergone an interview, clinical examination, multichannel
      urodynamic testing and 4D transperineal ultrasound. Ultrasound volume datasets of
      198 women were analysed retrospectively. Tomographic ultrasound imaging was used
      to diagnose levator avulsion at the time of the original assessment. To determine
      urethral mobility, data analysis was performed on a desktop PC using proprietary
      software several months later. The urethra was divided into 5 equal segments with
      6 points marked evenly along the urethra from the bladder neck (Point 1) to the
      external meatus (Point 6) as identified in the mid-sagittal view. Measurements of
      vertical and horizontal distances from the dorsocaudal margin of the pubic
      symphysis of these 6 points were taken in the mid-sagittal plane, using volume
      datatsets obtained at rest and on maximal Valsalva. Mobility vectors of these 6
      points were calculated using the formula SQRT ((x(valsalva)
      x(rest))(2)+(y(valsalva)-y(rest))(2)) and were correlated with levator status
      using two sample T tests. RESULTS: Levator avulsion was found in 18% of patients
      (n=35). Except at the bladder neck which almost reached significance (32.5mm in
      those with defects vs. 28.9 mm in those without, P=0.07), there was no
      significant association between urethral mobility and avulsion (all P>=0.17).
      CONCLUSION: Major levator trauma does not seem to substantially affect urethral
      mobility, with the possible exception of the bladder neck.

PMID- 20810203
TI  - When nausea becomes a tricky question.

PMID- 20810204
TI  - The effect of cholesterol on the reconstitution of alkaline phosphatase into
      liposomes.
AB  - Tissue-nonspecific alkaline phosphatase (TNAP), present on the surface of
      chondrocyte- and osteoblast-derived matrix vesicles (MVs), plays key enzymatic
      functions during endochondral ossification. Many studies have shown that MVs are
      enriched in TNAP and also in cholesterol compared to the plasma membrane. Here we
      have studied the influence of cholesterol on the reconstitution of TNAP into
      dipalmitoylphosphatidylcholine (DPPC)-liposomes, monitoring the changes in lipid
      critical transition temperature (T(c)) and enthalpy variation (?H) using
      differential scanning calorimetry (DSC). DPPC-liposomes revealed a T(c) of 41.5 
      degrees C and ?H of 7.63 Kcal mol(-1). The gradual increase in cholesterol
      concentration decrease ?H values, reaching a ?H of 0.87Kcalmol(-1) for
      DPPC:cholesterol system with 36mol% of cholesterol. An increase in T(c), up to 47
      degrees C for the DPPC:cholesterol liposomes (36 mol% of Chol), resulted from
      the increase in the area per molecule in the gel phase. TNAP (0.02 mg/mL)
      reconstitution was done with protein:lipid 1:10,000 (molar ratio), resulting in
      85% of the added enzyme being incorporated. The presence of cholesterol reduced
      the incorporation of TNAP to 42% of the added enzyme when a lipid composition of
      36 mol% of Chol was used. Furthermore, the presence of TNAP in proteoliposomes
      resulted in a reduction in ?H. The gradual proportional increase of cholesterol
      in liposomes results in broadening of the phase transition peak and eventually
      eliminates the cooperative gel-to-liquid-crystalline phase transition of
      phospholipids bilayers. Thus, the formation of microdomains may facilitate the
      clustering of enzymes and transporters known to be functional in MVs during
      endochondral ossification.

PMID- 20810205
TI  - PSCDGs of mouse multipotent adult germline stem cells can enter and progress
      through meiosis to form haploid male germ cells in vitro.
AB  - Spermatogonial stem cells (SSCs) provide the basis for spermatogenesis throughout
      adult life by undergoing self-renewal and differentiation into sperm. SSC-derived
      cell lines called multipotent adult germline stem cells (maGSCs) were recently
      shown to be pluripotent and to have the same potential as embryonic stem cells
      (ESCs). In a differentiation protocol using retinoic acid (RA) and based on a
      double selection strategy, we have shown that ESCs are able to undergo meiosis
      and produce haploid male germ cells in vitro. Using this differentiation protocol
      we have now succeeded to generate haploid male germ cells from maGSCs in vitro.
      maGSCs derived from a Stra8-EGFP transgenic mouse line were differentiated into
      stable spermatogonial stages and further cultured. These cells were transfected
      with a postmeiotic specific promoter construct Prm1-DsRed to monitor retinoic
      acid (RA) induced differentiation into haploid male gametes. Our protocol is
      another approach for the production of pluripotent stem cell derived gametes
      (PSCDGs) and is an alternative for the investigation of mammalian
      spermatogenesis, germ line gene modification and epigenetic reprogramming. If
      reproducible with pluripotent cell lines derived from human SSCs, it could also
      be used as a therapeutic approach for the treatment of male infertility.

PMID- 20810206
TI  - Vulnerability of Fraser River sockeye salmon to climate change: a life cycle
      perspective using expert judgments.
AB  - Fraser River sockeye salmon have been the basis for a major commercial fishery
      shared by Canada and the United States, and an important cultural foundation for
      many aboriginal groups; they are also of huge ecological significance throughout
      the Fraser Basin. The potential for altered aquatic habitat and temperature
      regimes due to climate change is an important concern for Fraser River sockeye
      salmon. This paper characterizes the vulnerability of Fraser River sockeye salmon
      to future climate change using an approach that is novel on three counts. First,
      previous efforts to assess the vulnerability of salmon to climate change have
      largely focused on only part of the life cycle, whereas we consider climate
      vulnerability at all stages in the life cycle. Second, we use the available
      scientific literature to provide a basis for structuring and eliciting judgments
      from fisheries science and management experts who research and manage these
      systems. Third, we consider prospects for mitigating the effects of climate
      change on sockeye salmon. Tests showed that participants' judgments
      differentiated in statistically significant ways among questions that varied in
      terms of life stages, spawning regions and climate scenarios. The consensus among
      participants was that Fraser River sockeye are most vulnerable to climate change
      during the egg and returning adult stages of the life cycle. A high temperature
      scenario was seen as imposing the greatest risk on sockeye stocks, particularly
      those that migrate to the upper reaches of the Fraser River system and spawn
      earlier in the summer. The inability to alter water temperature and the highly
      constrained nature of sockeye management, with competing gear types and
      sequential fisheries over a long distance, suggest the potential to mitigate
      adverse effects is limited. Fraser River sockeye already demonstrate a great deal
      of adaptive capacity in utilizing heterogeneous habitats in different river sub
      basins. This adaptability points to the potential value of policies to make
      stocks more resilient to uncertain futures.

PMID- 20810207
TI  - Assessing the impact of petrol stations on their immediate surroundings.
AB  - This paper describes a novel methodology for evaluating the extent to which
      petrol stations affect their surroundings. The method is based on the fact that
      the ratio of the concentrations of aliphatic and aromatic hydrocarbon pollutants
      in the air of the petrol stations and their surroundings (basically determined by
      vapor emissions from unburned gasoline) differs from the ratio found in urban
      air, which is mainly influenced by traffic emissions. Bearing this in mind, the
      spatial limit of influence of petrol stations in any direction would be the first
      point, moving away from the station, where the ratio becomes equal to the urban
      background ratio. Application of the methodology involves multipoint measuring
      campaigns of the air at the studied petrol station and built-up area in general
      and processing the data with software capable of providing isoconcentration
      contours. The procedure should help local authorities in terms of land
      management, so that a "belt" can be established around petrol stations where
      housing or vulnerable populations and activities such as those in schools,
      hospitals and community centers should be restricted.

PMID- 20810208
TI  - Nuclear Factor-kappaB modulates cellular glutathione and prevents oxidative
      stress in cancer cells.
AB  - The NF-kappaB is best known for its role in inflammation. Here we show that
      constitutive NF-kappaB activity in cancer cells promotes the biosynthesis of
      redox scavenger glutathione (GSH), which in turn confers resistance to oxidative
      stress. Inhibition of NF-kappaB significantly decreases GSH in several lines of
      human leukemia and prostate cancer cells possessing high or moderate NF-kappaB
      activities. Concomitantly, NF-kappaB inhibition by pharmacological and molecular
      means sensitizes "NF-kappaB positive" cancer cells to chemically-induced
      oxidative stress and death. We propose that inhibition of NF-kappaB can reduce
      intracellular GSH in "NF-kappaB-positive" cancers thereby improving the efficacy
      of oxidative stress-based anti-cancer therapy.

PMID- 20810209
TI  - Transmembrane transports of acrylamide and bisphenol A and effects on development
      of zebrafish (Danio rerio).
AB  - Acrylamide (AA) and bisphenol A (BPA) are two kinds of pollutants with different
      structures and polarities. AA found in fried and toasted starchy foods can cause
      developmental and reproductive toxicity and BPA has neuro-, immuno- and
      developmental toxicities. Their transports in zebrafish (Danio rerio) embryos
      were determined and their toxicity characteristics observed. Approximately 70% of
      AA was concentrated on the outer membrane surface probably via hydrogen bonds and
      van der Waals forces, but only 0.3% of AA entered the cytoplasm. In contrast,
      over 10% of the BPA adsorbed to the cells entered the cytoplasm via the membrane
      by lipid-water partition. The hydrophilic AA and hydrophobic BPA used different
      cell transport pathways; AA accumulated on the outer membrane surface whereas BPA
      readily reached the cytoplasm. AA caused acute and indirect toxicity in
      developing cells, including serious malnutrition and axial malformation. BPA
      caused chemical damage to developing cells by causing pericardial edema. The
      antagonistic effect of the AA/BPA mixture's combinational toxicity to embryos was
      found and explained by the accumulation of AA on the out surface of membrane
      inhibiting the transfer of BPA to the cytoplasm.

PMID- 20810210
TI  - Ozone decomposition on Ag/SiO2 and Ag/clinoptilolite catalysts at ambient
      temperature.
AB  - Silver modified zeolite (Bulgarian natural clinoptilolite) and Ag/silica
      catalysts were synthesized by ion exchange and incipient wet impregnation method
      respectively and characterized by different techniques. DC arc-AES was used for
      Ag detection. XRD spectra show that Ag is loaded over the surface of the SiO(2)
      sample and that after the ion-exchange process the HEU type structure of
      clinoptilolite is retained. UV-VIS (specific reflection at 310 nm) and IR (band
      at 695 cm(-1)) spectroscopy analysis proved that silver is loaded as a T-atom
      into zeolite channels as Ag(+), instead of Na(+), Ca(2+), or K(+) ions, existing
      in the natural clinoptilolite form. The samples Ag/SiO(2) and Ag-clinoptilolite
      were tested as catalysts for decomposition of gas phase ozone. Very high
      catalytic activity (up to 99%) was observed and at the same time the catalysts
      remained active over time at room temperature.

PMID- 20810211
TI  - The impact of zero-valent iron nanoparticles on a river water bacterial
      community.
AB  - Zero-valent iron (ZVI) nanoparticles are of interest because of their many
      potential biomedical and environmental applications. However, these particles
      have recently been reported to be cytotoxic to bacterial cells. The overall
      objective of this study was to determine the impact of 100mg/L ZVI nanoparticles
      on the diversity and structure of an indigenous river water bacterial community.
      Response during exposure for 36 days was determined by denaturing gel gradient
      electrophoresis (DGGE) analysis of bacterial 16S rRNA genes, amplified from
      extracted DNA, and viable and total cell abundances were determined by plate
      counting and fluorescent microscopy of DAPI-stained cells. Changes in river water
      chemistry were also monitored. Addition of ZVI nanoparticles led to a rapid
      decrease in oxidation-reduction potential (ORP) (+196 to -281 mV) and dissolved
      oxygen (DO) concentration (8.2-0.6 mg/L), both of which stabilized during the
      experiment. Interestingly, both viable and total bacterial cell abundances
      increased and pH decreased, characteristic of an active microbial community.
      Total community structure was visualized using rank-abundance plots fitted with
      linear regression models. The slopes of the regression models were used as a
      descriptive statistic of changes in evenness over time. Importantly, despite
      bacterial growth, addition of ZVI nanoparticles did not influence bacterial
      community structure.

PMID- 20810212
TI  - Preparation and characterization of chelating fibers based on natural wool for
      removal of Hg(II), Cu(II) and Co(II) metal ions from aqueous solutions.
AB  - The graft copolymerization of acrylonitrile (AN) onto natural wool fibers
      initiated by KMnO(4) and oxalic acid combined redox initiator system in limited
      aqueous medium was carried out in heterogeneous media. Moreover, modification of
      the grafted wool fibers was done by changing the nitrile group (-CN) into cyano
      acetic acid alpha-amino-acrylic-hydrazide through the reaction with hydrazine
      hydrate followed by ethylcyanoacetate which eventually produce wool-grafted
      poly(cyano-acetic acid alpha-amino-acrylic-hydrazide) (wool-g-PCAH) chelating
      fibers. The application of the modified fibers for metal ion uptake was studied
      using Hg(2+), Cu(2+) and Co(2+). The modified chelating fibers were characterized
      using FTIR spectroscopy, SEM and X-ray diffraction.

PMID- 20810213
TI  - Facile synthesis of ZnO/Zn2TiO4 core/shell nanowires for photocatalytic oxidation
      of acetone.
AB  - ZnO/Zn(2)TiO(4) core/shell nanowires were synthesized for the first time based on
      a solid-solid reaction of ZnO nanowires with a conformal shell of TiO(2), which
      was deposited by a sol-gel method. The as-prepared samples were characterized by
      X-ray diffraction (XRD) analysis, transmission electron microscope (TEM) and
      environmental scanning electron microscope (ESEM). The surface photovoltage (SPV)
      spectra indicated that the as-synthesized ZnO/Zn(2)TiO(4) core/shell nanowires
      exhibited more excellent photovoltaic activity than single ZnO nanowires. The
      enhanced photocatalytic activity of the ZnO/Zn(2)TiO(4) core/shell nanowires was
      demonstrated by the degradation of acetone under UV light irradiation. As
      monitored by the in situ FTIR, a sequence of chemical steps could be extracted
      during the photocatalytic oxidation of gaseous acetone, which was firstly
      degraded into formate, and subsequently converted into CO and CO(2). CO(2) was
      partially converted to carbonate further.

PMID- 20810214
TI  - Numbers-needed-to-treat analyses--do timing, dropouts, and outcome matter? Pooled
      analysis of two randomized, placebo-controlled chronic low back pain trials.
AB  - Numbers-needed-to-treat (NNT) are useful for presenting treatment response,
      conveying the clinical relevance of results. NNTs are typically calculated at a
      landmark endpoint (end of trial), but often using the last observation carried
      forward (LOCF), which ignores patient discontinuations. We compared NNTs in
      chronic low back pain (CLBP) using three separate imputation methods, using data
      from two identical 12-week trials comparing etoricoxib 60 mg (N=210), 90 mg
      (N=212), and placebo (N=217). We calculated the number of patients with
      improvements in pain intensity from baseline of >=15%, >=30%, >=50%, and >=70% at
      2, 4, 8, and 12 weeks of treatment. For longitudinal response over time, patient
      discontinuations were assigned a 0% improvement from dropout forward. Landmark
      response at week 12 was assessed using LOCF and completer approaches, using only
      observed (non-missing) data. The longitudinal approach was most conservative;
      after 12 weeks 65% of patients taking etoricoxib had >=15% improvement, 60% had
      >=30% improvement, 45% had >=50%, improvement, and 30% had >=70% improvement,
      with placebo rates approximately 55%, 45%, 30%, and 15%, respectively. Response
      rates were higher with landmark analyses. Landmark NNTs at week 12 were generally
      similar or slightly lower (better) than those from a longitudinal approach, but
      results were inconsistent. Landmark analyses provide no information on response
      variability, as is obtained with longitudinal analysis. Outcome, imputation
      method, and reporting method are intimately connected and need to be considered
      alongside trial quality and validity to make sensible comparisons between
      treatments.

PMID- 20810215
TI  - Effects of doxycycline on the endosymbiont Wolbachia in Dirofilaria immitis
      (Leidy, 1856)--naturally infected dogs.
AB  - Dirofilaria immitis carries intracellular endosymbiotic bacteria of the genus
      Wolbachia, known to be vital for the worms and sensitive to tetracycline
      antibiotics. With the purpose of studying the interaction between D. immitis and
      the endosymbiont Wolbachia sp., heartworm naturally infected microfilaremic or
      antigenemic dogs were treated with doxycycline (10mg/kg/day of the drug in three
      cycles of 21 days each, with 6-month intervals). Blood samples were collected on
      days 0, 7 and 21 of each treatment as well as on day 111 after the beginning of
      each cycle. A final sample was collected on day 723 from the beginning of the
      first treatment. The samples were examined for the presence and number of
      microfilariae and the presence of antigen as well as the presences of D. immitis
      and Wolbachia sp. DNA using PCR (polymerase chain reaction). With this approach,
      an evaluation of the effect of doxycycline on antigenemia and on the presence of
      Wolbachia sp. DNA in dogs with heartworm infection was possible. Doxycycline
      treatment did not alter the detection of adult parasite antigens with the
      exception of two animals, though the number of animals carrying Wolbachia sp. DNA
      decreased, despite the presence of the microfilariae. The effect of the
      antibiotic therapy on the worms may have interfered with the transmission of
      heartworm disease because the population of microfilariae and the number of
      microfilaremic dogs were reduced and the microfilariae positive samples that were
      found did not test positive for Wolbachia sp. in many cases. These findings
      suggest that in areas were doxycycline is extensively used D. immitis
      transmission may be impaired by the reduction on the number of microfilariae and
      on the endosymbiotic bacteria in the larvae turning them incapable of completing
      development once they infected a new host.

PMID- 20810216
TI  - Comparison between ELISA using total antigen and immunochromatography with
      antigen rK39 in the diagnosis of canine visceral leishmaniasis.
AB  - In this study, an enzyme-linked immunosorbent assay using crude total antigen
      (CTA-ELISA) and immunochromatography with antigen rK39 were compared in the
      diagnosis of canine visceral leishmaniasis (CVL). Fifty-two total blood samples
      from symptomatic dogs obtained from a location endemic for leishmaniasis and 52
      blood samples from healthy dogs from a nonendemic region were tested. Polymerase
      chain reaction (PCR) was used to detect DNA from Leishmania spp. in both groups.
      Symptomatic dogs with positive PCR were considered infected by Leishmania spp.
      and the PCR technique was chosen as a gold standard test. The sensitivity
      determined for CTA-ELISA was 100%, with specificity of 91.2%, while the
      immunochromatographic assay with the antigen rK39 showed sensitivity of 91.5%,
      with specificity of 94.7%. A strong correlation was verified between CTA-ELISA
      and immunochromatography with antigen rK39, with a kappa coefficient of agreement
      of 0.88. Analysis of the results suggested that both assays presented good
      sensitivity and specificity for diagnosing CVL; however, immunochromatography
      with the antigen rK39 may be more advantageous when a fast field test is
      required.

PMID- 20810217
TI  - A cross-sectional survey of gastrointestinal parasites with dispersal stages in
      feces from Costa Rican dairy calves.
AB  - A cross-sectional study was carried out to determine the prevalence of
      gastrointestinal parasites and lungworm nematodes in dairy calves from five
      different ecoclimatic areas of Costa Rica. Also intensity of infection of
      nematodes was determined. In order to describe management practices and
      anthelmintic control, a questionnaire was applied in 73 farms. The influence of
      area, farm, host (breed, age) and ecological factors (low and high rainfall
      period) upon eggs per gram feces (epg) of gastrointestinal nematodes (GIN) and
      first larval stage counts (L1) of Dictyocaulus viviparus were investigated.
      Furthermore, association of host, ecological and management risk factors to the
      prevalence of gastrointestinal parasites and D. viviparus were analyzed. The most
      prevalent GIN, cestodes and protozoan identified in dairy farms were similar in
      all areas studied. Strongylidae was the most prevalent parasite group detected,
      represented mainly by Haemonchus spp. and Cooperia spp., whereas Ostertagia spp.
      and Mecistocirrus digitatus were barely found. The most prevalent protozoan was
      Eimeria spp. The questionnaire applied to producers revealed the following
      management practices: weaning age of calves 1-4 months (52.1%), semi-confinement
      of calves upon 5-8 months of age (41.1%), number of paddocks used for calves <10
      (57.5%), first deworming of calves at ages >=15 days (74.70%) and deworming of
      calves at intervals >60 days (52.1%). Anthelmintic products were changed in 56.1%
      of the farms at intervals between 13 and 24 months. Although 91.8% of the farms
      had veterinary assistance, the majority performed parasite control regimes
      according to the criteria of the producers (66.7%). Common practices were the
      dispersion of animal feces on the pastures (64.4%) and use of disinfectant in the
      milking room (63.4%). The analyses of variance showed significant influence
      (p<0.05) of age, rainfall period, interaction of rainfall period on area
      (rainfall period*area) and nested effect of farm within area [farm (area)] on epg
      of Strongylidae; age, area, rainfall period*area and [farm (area)] on epg of
      Strongyloides papillosus; age, rainfall period and farm (area) on epg of
      Trichuris spp.; rainfall period, rainfall period*area and [farm (area)] on L1 of
      D. viviparus. The logistic regression analyses determined area, semi-confinement,
      management of feces, use of disinfectant in the milking room as risk factors for
      the presence of Strongylidae, S. papillosus and Trichuris spp; rainfall, age,
      paddock numbers for D. viviparus; and area, age, veterinary assistance, deworming
      program, age at first deworming and use of disinfectant in the milking room for
      Eimeria spp. and Buxtonella sulcata.

PMID- 20810218
TI  - Occurrence of Hepatozoon sp. in dogs in the urban area originating from a
      municipality in southeastern Brazil.
AB  - The occurrence of Hepatozoon sp. infection in dogs was evaluated in the urban
      area of Uberlandia, Minas Gerais, Brazil. The study involved 300 animals, 120
      from the Veterinary Hospital of the Federal University of Uberlandia's Faculty of
      Veterinary Medicine, 80 from private clinics, and 100 from the Animal Protective
      Association (APA). Among these animals, 7.66% presented Hepatozoon sp. gamonts
      inside neutrophils. No statistically significant difference was found among the
      diagnoses based on capillary and venous blood smears, but a statistical
      significance was identified in age range and breed. The main signs and symptoms
      the animals presented were pale mucous membranes, swollen lymph nodes, ocular
      discharge and pain in response to renal palpation. All the ticks collected were
      of the species Rhipicephalus sanguineus and no oocyst of the parasite was found
      in the hemolymph of the ixodidae. The findings of this study reinforce the
      presence of Hepatozoon sp. infecting dogs in Uberlandia, MG, with age and breed
      possibly related to the infection. The symptoms presented by the animals were
      consistent with those reported by other researchers.

PMID- 20810220
TI  - I didn't feel like drinking but I don't know why: the effects of evaluative
      conditioning on alcohol-related attitudes, craving and behavior.
AB  - The goal of the present research was to test the value of evaluative conditioning
      (EC) to unobtrusively change alcohol-related attitudes and drinking behavior. In
      the EC paradigm, participants had to spot an irrelevant target picture in a
      series of trials in which many different stimuli were presented. In the
      experimental condition, beer-related pictures (CSs) were consistently paired with
      negative words and pictures (USs) in a number of trials. In the control
      condition, participants were exposed to the same stimuli, but without the
      critical alcohol-negative pairings. After the EC task, participants participated
      in an allegedly second experiment in which we measured beer-related attitudes,
      craving for beer, and actual drinking behavior both during a bogus taste test and
      during the week following the experiment. Compared to participants in the control
      condition, participants in the experimental condition showed more negative
      attitudes toward beer, experienced less craving for beer, and consumed less beer
      both in the lab during the taste test and outside the lab during the week
      following the manipulation. These findings suggest that unhealthy drinking
      behavior may be targeted through EC procedures.

PMID- 20810221
TI  - Considerations concerning design and mechanism of action of a new class of
      anticancer dual DNA intercalators.
AB  - Cancer is one of the most serious and merciless health problems of the mankind,
      about seven million people dying of cancer every year. Two of the most important
      and promising targets in cancer chemotherapy include DNA alkylating agents and
      DNA intercalators. The emphasis of this work was to design, synthetize and
      formulate a mechanism of action for a new class of dual DNA intercalators. The
      dual DNA intercalators have three main parts: an alkylating unit (represented by
      two halo-alkyl-ester chains), an intercalator unit (five- or six-membered ring
      nitrogen heterocycle) and an acetophenone skeleton linker. As mechanism of
      action, we consider that these compounds act as dual DNA intercalators, the
      alkylating unit realizing a covalent bonding via DNA protein "cross-linking
      effect" while nitrogen heterocycles will realize noncovalent bonding via DNA
      intercalation with purine and pyrimidine bases from DNA and the amino acids from
      topoisomerases enzymes. Our hypothesis was confirmed by in vitro anticancer tests
      against HeLa cell lines, where the newly obtained compounds demonstrated a very
      good activity.

PMID- 20810219
TI  - Differences in regional brain metabolism associated with specific formulations of
      hormone therapy in postmenopausal women at risk for AD.
AB  - Differential cerebral metabolic effects of various hormone therapy formulations,
      and their associations with cognitive status, remain to be established. The
      principal aim of the current study was to assess relationships between regional
      cerebral metabolism and estrogen-based hormone therapies. Postmenopausal women
      (n=53) at elevated risk for Alzheimer's disease (AD) were on estrogen-containing
      hormone therapy for at least one year prior to enrollment in a prospective,
      randomized clinical trial. Subjects underwent an FDG-PET scan, along with
      neuropsychological, medical, and demographic assessments at time of enrollment,
      to be repeated one year following randomization to hormone therapy continuation
      versus discontinuation, and results from analyses of the baseline assessments are
      reported here. Across all subjects, years of endogenous estrogen exposure
      correlated most closely with metabolism in right superior frontal gyrus
      (p<0.0005). Women taking 17beta-estradiol (E) performed three standard deviations
      higher in verbal memory than women taking conjugated equine estrogen (CEE), and
      their verbal memory performance positively correlated with metabolism in
      Wernicke's (p=0.003) and auditory association (p=0.002) areas. Women taking
      progesterone-plus-estrogen had lower metabolism than women taking unopposed
      estrogen within the mesial and inferior lateral temporal regions (p<0.0005) and
      the inferior frontal cortex, contralateral to Broca's area (p<0.0005). In
      conclusion, particular areas of relatively preserved metabolism were seen in
      women with more years of endogenous estrogen exposure, as well as in women taking
      estradiol-based formulations or estrogen therapies unopposed by progesterone,
      together suggesting regionally specific neuroprotective estrogenic effects.

PMID- 20810222
TI  - Prevention of coronary artery disease in men: male hormone, female hormone, or
      both?
AB  - Sex hormones play an important role in coronary artery disease. Although both
      male and female hormones have been well-documented to be able to influence
      vascular biology, the preventive use of sex hormones in CAD is not established.
      Recent progress suggests a necessity of rethinking of the use of sex hormones for
      CAD in both sexes. We hypothesize that a long-term and appropriate low-dose
      combination of male hormone and female hormone could be an effective preventive
      strategy for men with a high risk of but not developed CAD. This hypothesis is
      supported by the fact that estrogen has favorable profiles on several key CAD
      associated risk factors regardless of sexes. Testosterone supplementation has
      been linked to a reduced risk of CAD specifically in men. In animal models the
      reduced risk of CAD in males administrated with testosterone is due to the
      conversion of testosterone into estrogen; and sex hormone ratio changes rather
      than each individual sex hormone were found to be the predictor of CAD in a human
      study, suggesting the importance of a proper ratio of estrogen:testosterone in
      the development of CAD. In addition, the controversy surrounding the use of
      hormone replacement therapy in women in turn indicates a potential beneficial
      effect of sex hormones in men in the prevention of CAD because of the fundamental
      difference between sexes. Therefore, the combined use of estrogen and
      testosterone for CAD in men deserves a full investigation and could provide
      useful information in understanding of the preventive and/or therapeutic
      application of sex hormones in both sexes.

PMID- 20810223
TI  - Crystal methamphetamine use among female street-based sex workers: Moving beyond
      individual-focused interventions.
AB  - Given growing concern of the sexual risks associated with crystal methamphetamine
      use and the dearth of research characterizing the use of methamphetamine among
      street-based sex workers (FSWs), this study aimed to characterize the prevalence
      and individual, social, and structural contexts of crystal methamphetamine use
      among FSWs in a Canadian setting. Drawing on data from a prospective cohort, we
      constructed multivariate logistic models to examine independent correlates of
      crystal methamphetamine among FSWs over a two-year follow-up period using
      generalized estimating equations. Of a total of 255 street-based FSWs, 78 (32%)
      reported lifetime crystal methamphetamine use and 24% used crystal
      methamphetamine during the two-year follow-up period, with no significant
      associations between methamphetamine use and sexual risk patterns. In a final
      multivariate GEE model, FSWs who used crystal methamphetamine had a higher
      proportional odds of dual heroin injection (adjOR=2.98, 95%CI: 1.35-5.22), having
      a primary male sex partner who procures drugs for them (adjOR=1.79, 95%CI: 1.02
      3.14), and working (adjOR=1.62, 95%CI: 1.04-2.65) and living (adjOR=1.41, 95%CI:
      1.07-1.99) in marginalized public spaces. The findings highlight the crucial need
      to move beyond the individual to gender-focused safer environment interventions
      that mediate the physical and social risk environment of crystal methamphetamine
      use among FSWs.

PMID- 20810224
TI  - Effect of Ergosan on semen quality of male rainbow trout (Oncorhynchus mykiss)
      broodstock.
AB  - Present study was conducted to investigate the effect of Ergosan on seminal
      plasma compositions and spermatological parameters in rainbow trout. Male rainbow
      trout broodstocks (2300 +/- 200 g) were fed diets containing Ergosan at 2
      different concentrations (6 mg kg(-1) and 20 mg kg(-1)) and control diet without
      Ergosan for 20 days and on day 22 fish semen were sampled. Results suggest that
      Ergosan in dietary intake, significantly increased the spermatocrit and sperm
      count in 20 mg kg(-1) group and Ca(2+) in both treatment groups compared to
      control group (P<0.05). The values of aspartate aminotransferase (AST) and
      lactate dehydrogenase (LDH) had significant decrease in both treatment groups
      compared to the control group (P<0.05). Significant correlations were determined
      between sperm count versus K(+) value (r=-0.838, P<0.05) and glucose level
      (r=+0.835, P<0.05) in fish administrated with 20 mg kg(-1) of Ergosan. In group
      treated with 6 mg kg(-1), significant correlation between Na(+) and duration of
      sperm motility (r=+0.999, P<0.05) was shown. Meanwhile, glucose level versus
      percent of sperm motility (r=+0.866, P<0.05) showed significant correlation in
      this group. Sperm count versus total protein level (r=+0.817, P<0.05) showed
      significant correlation in control group. Results indicated that Ergosan had a
      potential efficacy on semen quality in rainbow trout broodstock.

PMID- 20810225
TI  - Screening for illicit drugs on Euro banknotes by LC-MS/MS.
AB  - A method for the simultaneous quantification of illicit drugs on Euro banknotes,
      using an ultra-performance liquid chromatography tandem mass spectrometry, was
      developed and validated. The method included cocaine, benzoylecgonine, MDMA,
      MDEA, MDA, methamphetamine, diacetylmorphine, 6-MAM, morphine and Delta(9)-THC.
      Drug residues were monitored and quantified via positive ESI mode using multiple
      reaction monitoring. Banknotes were extracted with methanol by vigorous shaking.
      Recovery rates were in the range of 60-80%. Calibration was performed with spiked
      banknotes in the range of 10-100 ng/note (R(2) 0.98-0.99). Intra-day analysis
      showed fair precision and accuracy (<= 15%). Matrix effects were in the range
      from 27% to 235%. 7-15 samples of each denomination were analyzed. The calculated
      median values per note were 106 ng cocaine, 43 ng benzoylecgonine, 41 ng heroin,
      15.5 ng 6-MAM, 16.5 ng morphine, 9 ng MDMA and 7 ng methamphetamine. Delta(9)-THC
      was detected on 4 banknotes. MDEA and MDA were not detected on any note. A
      widespread background contamination for cocaine and opiates was demonstrated.

PMID- 20810226
TI  - Use of Glasgow Benefit Inventory (GBI) in Meniere's disease managed with
      intratympanic dexamethasone perfusion: Quality of life assessment.
AB  - OBJECTIVE: To evaluate patients' quality of life following intratympanic
      dexamethasone perfusion in management of Meniere's disease (MD). METHODS: This is
      a retrospective study in a tertiary referral center that uses the Glasgow Benefit
      Inventory (GBI). Intratympanic perfusion of 24mg/ml of dexamethasone was
      administered after failure to respond to previous management with diuretics and
      low-salt diet. GBI questionnaires were collected and analyzed in a 12 months
      follow-up of participating patients. RESULTS: Thirty patients (20 women and 10
      men, aged 28-85 years) with MD underwent intratympanic dexamethasone perfusion
      and were assessed with the assistance of GBI questionnaire. Follow-up ranged from
      12 to 48 months (mean 30 months). Audiometric results were also available in all
      of them. In the short term (4 weeks post-perfusion) 6 patients demonstrated a
      greater than 10dB improvement in PTA, and 6 patients had an increase in SDS of at
      least 15%, while in the long-term (12 months post-perfusion) the number of
      patients in the respective groups decreased to 5 and 2. With regards to the GBI
      responses, 9 patients (50%) expressed an overall benefit, while 6 (33%) expressed
      no benefit and 3 patients (17%) complained of negative effect after the
      intervention. CONCLUSION: The mean GBI score indicates substantial improvement in
      patients' overall quality of life following intratympanic dexamethasone
      perfusion, which was also confirmed by the audiometric results.

PMID- 20810227
TI  - The long-term effect of ursodeoxycholic acid on  laboratory liver parameters in
      biochemically  non-advanced primary biliary cirrhosis.
AB  - BACKGROUND AND AIMS: Ursodeoxycholic acid (UDCA) has an established effect on
      liver bio-chemistries in primary biliary cirrhosis (PBC). Few studies have
      evaluated long-term laboratory treatment effects and data beyond 6 years are not
      available. The aim of this study was to assess the long-term evolution of liver
      bio-chemistries during prolonged treatment with UDCA in biochemically non
      advanced PBC. PATIENTS AND METHODS: Prospective multicenter cohort study of
      patients with PBC with pretreatment normal bilirubin and albumin, treated with
      UDCA 13-15 mg/kg/day. At yearly intervals, follow-up data including serum
      bilirubin, alkaline phosphatase (ALP), transaminases, albumin and IgM were
      collected. Data were analyzed with a repeated measurement model. RESULTS: Two
      hundred and twenty-five patients were included and followed during a median
      period of 10.3 years. Following 1-year treatment with UDCA 36-100% of the total
      biochemical improvement was achieved, the maximum response was observed after 3
      years. After initial improvements, bilirubin and AST levels increased and albumin
      levels significantly decreased after 6-10 years. However, these changes were of
      limited magnitude. The beneficial effects on ALT and ALP were maintained while
      IgM continued to decrease. CONCLUSION: In non-advanced PBC the biochemical
      response to UDCA is maintained up to 15 years. The long-term evolution of
      bilirubin, albumin and ALT differs from that of ALP and AST. The mean IgM level
      normalised and levels continued to decrease during the period of follow-up.

PMID- 20810228
TI  - Abdominal lymphatic tuberculosis and portal hypertension.
AB  - Abdominal tuberculosis involving the portal vasculature is a rare phenomenon. We
      retrospectively reviewed the imaging findings of 183 cases of abdominal
      tuberculosis at our institution from 2002 to 2010 and found thrombosis of the
      splenoportal axis associated with abdominal lymphadenopathy in seven patients.
      However, there was no relationship between the lymph nodal size and development
      of thrombosis. Reversibility was noted in one patient, who had near complete
      recanalisation of portal vein. Mechanisms, other than direct mass effect on the
      splenoportal axis, may be involved, like contiguous spread of inflammation or
      granulomas in the vessel wall.

PMID- 20810229
TI  - Attenuation-based characterization of coronary atherosclerotic plaque: comparison
      of dual source and dual energy CT with single-source CT and histopathology.
AB  - OBJECTIVE: To compare different CT acquisition techniques regarding for
      attenuation-based characterization of coronary atherosclerotic plaques using
      histopathology as the standard of reference. MATERIALS AND METHODS: In a post
      mortem study 17 human hearts were studied with dual-source CT (DSCT) and dual
      energy CT (DECT) mode on a DSCT as well as with 16-slice single-source CT (SSCT).
      At autopsy, atherosclerotic lesions were cut at 5 MUm sections. Histopathologic
      classification of the plaques according to the American Heart Association (AHA)
      criteria was performed by two pathologists. Attenuation values of all plaques
      were measured in DSCT, DECT and SSCT studies, respectively and classified based
      on attenuation according to modified AHA criteria. RESULTS: 58 coronary plaques
      were identified at autopsy. Regardless of the CT technique only 52/58 plaques
      were found at CT (sensitivity=89.6%). There was no significant difference between
      the mean attenuation values of different plaque types between DSCT, DECT, and
      SSCT: type IV: 11HU/8HU/19HU; type Va: 44HU/45HU/52HU; type Vb:
      1088HU/966HU/1079HU). The sensitivity for correct classification varied depending
      on the plaque type (type II=0%, type III=0%, type IV=43%, type Va=58%, Vb=97%).
      CONCLUSION: Independent of the used acquisition technique, SSCT, DSCT and DECT
      show similar results for attenuation-based characterization of atherosclerotic
      coronary plaques.

PMID- 20810230
TI  - The role of dynamic contrast-enhanced and diffusion weighted magnetic resonance
      imaging in the female pelvis.
AB  - Functional imaging by means of dynamic multiphase contrast-enhanced magnetic
      resonance imaging (DCE-MRI) and diffusion weighted magnetic resonance imaging (DW
      MRI) is now part of the standard imaging protocols for evaluation of the female
      pelvis. DCE-MRI and DW-MRI are important MR imaging techniques which enable the
      radiologist to move from morphological to functional assessment of diseases of
      the female pelvis. This is mainly due to the limitations of morphologic imaging,
      particularly in lesion characterization, accurate lymph node staging, assessment
      of tumour response and inability to differentiate post-treatment changes from
      tumour recurrence. DCE-MRI improves the accuracy of T2WI in staging of
      endometrial cancer. It also helps differentiate tumour recurrence from radiation
      fibrosis in patients with cervical cancer. DCE-MRI improves characterization of
      cystic adnexal lesions and detection of small peritoneal implants in patients
      with ovarian cancer. DW-MRI is valuable in preoperative staging of patients with
      endometrial and cervical cancer, especially in detection of extra-uterine
      disease. It does increase reader's confidence for detection of recurrent disease
      in gynaecological malignancies and improves detection of small peritoneal
      implants in patients with ovarian cancer. In this review article we give an
      overview of both DCE-MRI and DW-MRI techniques, concentrating on their main
      clinical application in the female pelvis, and present a practical approach of
      the added value of these techniques according to the main pathological
      conditions, highlighting the pearls and pitfalls of each technique.

PMID- 20810231
TI  - 18FDG PET for grading malignancy in thymic epithelial tumors: significant
      differences in 18FDG uptake and expression of glucose transporter-1 and
      hexokinase II between low and high-risk tumors: preliminary study.
AB  - PURPOSE: To evaluate (18)F-fluorodeoxyglucose (FDG) uptake to predict the
      malignant nature and analyze the correlation between FDG uptake and expression of
      glucose transporter 1 (Glut-1) and hexokinase II (HK-II) in thymic epithelial
      tumors. MATERIALS AND METHODS: Eleven patients with a thymic epithelial tumor who
      underwent FDG PET/CT before therapy were reviewed. The thymic tumors were
      classified by the WHO histological classification and Masaoka clinical staging.
      Comparison of maximum standardized uptake value (SUV(max)) of the lesion was made
      between the low-risk (Type A, AB and B1) and high-risk {Type B2, B3 and C (thymic
      cancer)} groups and among clinical stages. Expression of Glut-1 and HK-II was
      analyzed immunohistochemically. RESULTS: All 11 tumors showed FDG uptake
      visually. SUV(max) was significantly higher in the high-risk group (n=5, 5.24 +/-
      2.44) than the low-risk group (n=6, 3.05 +/- 0.55) (P=0.008). Staining scores of
      both Glut-1 and HK-II were significantly higher in the high-risk group than in
      the low-risk group (Glut1: P=0.034 and HK-II: P=0.036). There were no significant
      differences in SUV(max) (P=0.11), Glut-1 (P=0.35) and HK-II scores (P=0.29) among
      clinical stages. SUV(max) was significantly correlated to each of the staining
      scores of Glut-1 (rho=0.68, P=0.031) and HK-II (rho=0.72, P=0.024). CONCLUSION:
      These preliminary results support the previously published view that SUV(max) may
      be useful to predict the malignant nature of thymic epitherial tumors and suggest
      that the degree of FDG uptake in the thymic epitherial tumors is closely related
      to the amount of Glut-1 and HK-II in the tumor.

PMID- 20810232
TI  - Lung cancer growth dynamics.
AB  - Mathematical modeling furnishes valuable and otherwise unattainable insights,
      some counterintuitive, into the natural history of lung cancer. We modeled lung
      cancer growth dynamics to show that: (1) early diagnosis of lethal lung cancer by
      means of radiographic or CT screening is an unattainable goal. (2) At a given
      dimension and constant tumor volume doubling time, the rate of diameter increase
      is an exponential function (base 1.26) of the number of tumor volume doublings,
      and the rate of increase in volume, a quadratic function of the radius. (3) This
      methodology delineates the magnitude of diameter increase in small nodules
      required to discern volume growth. (4) Under the assumption of a high degree of
      compliance with sequential screens in large-scale trials, mean tumor volume
      doubling time can be estimated from the prevalence:incidence ratio. For example,
      in the Mayo Clinic computerized tomography trial, stage IA tumor volume doubling
      time was 230 days.

PMID- 20810233
TI  - Targeting EGFR-overexpressing tumor cells using Cetuximab-immunomicelles loaded
      with doxorubicin and superparamagnetic iron oxide.
AB  - Epidermal growth factor receptor (EGFR), a cellular transmembrane receptor, plays
      a key role in cell proliferation and is linked to a poor prognosis in various
      human cancers. In this study, we constructed Cetuximab-immunomicelles in which
      the anti-EGFR monoclonal antibody was linked to poly(ethylene glycol)-block
      poly(E-caprolactone) (PEG-PCL) nanomicelles that were loaded with doxorubicin
      (DOX) and superparamagnetic iron oxide (SPIO). The specific interactions between
      EGFR-overexpressing tumor cells (A431) and immunomicelles were observed using
      confocal laser scanning microscopy (CLSM) and flow cytometry. Furthermore, the
      capacity of transporting SPIO into tumor cells using these immunomicelles was
      evaluated with a 1.5 T clinical magnetic resonance imaging (MRI) scanner. It was
      found that the acquired MRI T2 signal intensity of A431 cells that were treated
      with the SPIO-loaded and antibody-functionalized micelles decreased
      significantly. Using the thiazolyl blue tetrazolium bromide (MTT) assay, we also
      demonstrated that the immunomicelles inhibited cell proliferation more
      effectively than their nontargeting counterparts. Our results suggest that
      Cetuximab-immunomicelles are a useful delivery vehicle for DOX and SPIO to EGFR
      overexpressing tumor cells in vitro and that Cetuximab-immunomicelles can serve
      as a MRI-visible and targeted drug delivery agent for better tumor imaging and
      therapy.

PMID- 20810234
TI  - [Guidelines for clinical practice for bariatric surgery].
AB  - Bariatric surgery is intended for subjects with BMI >= 40 kg/m(2) or >= 35
      kg/m(2) with comorbidities. In any case, the indication can only be envisaged in
      patients who have had access to specialized medical care, and agree with a
      prolonged medical follow-up. After 60 years old, physiological age and
      comorbidities need to be highly considered. In genetic obesity and
      craniopharyngioma, surgery is exceptional. Main contraindications consist in
      severe disorders in feeding behaviour, non-stabilized psychiatric disorders,
      alcoholism, drug addiction, inability to participate in prolonged medical follow
      up. Surgical process includes many important stages: preparation and information
      by a multidisciplinary team (identify contraindication, give optimal information,
      look for and treat comorbidities [as sleep apneoas syndrome, diabetes,
      cardiopulmonary disease], assess nutritional and psychological status and feeding
      behaviour); the decision of intervention during a concerted analysis by a
      multidisciplinary team; follow-up (for life) led to screen for nutritional
      deficiencies and surgical complications, to reinforce diet and physical activity
      counselling, to adapt to new situations (as pregnancy), and advise psychological
      care if necessary.

PMID- 20810235
TI  - Minimally invasive anterior approach with a fracture table for total hip
      arthroplasty. Letter to the editor.

PMID- 20810236
TI  - A late vascular complication due to component migration after revision total hip
      arthroplasty.
AB  - Although vascular injuries associated with primary and revision total hip
      arthroplasty are infrequent, these complications can have devastating effects
      that can lead to morbidity and even mortality. No previous reports have described
      embolic distal limb ischemia secondary to a failed and migrated acetabular
      implant in discontinuity with the pelvis. We present a novel case in which a
      screw from a failed and migrated acetabular cage construct led to injury of the
      superficial femoral artery. While awaiting the construction of a custom
      prosthesis, the patient developed thromboembolism leading to distal extremity
      ischemia. The patient was treated with thrombolytic therapy, anticoagulation,
      removal of the offending hardware, forefoot amputation, and later hip
      reconstruction. Recognition of the risks associated with failed and migrated
      components may prevent this complication in the future.

PMID- 20810237
TI  - Total knee arthroplasty after failed distal femoral varus osteotomy using
      selectively stemmed posterior stabilized components.
AB  - The purpose of this study was to evaluate the outcomes of patients treated with
      total knee arthroplasty (TKA) for progression of arthritis after distal femoral
      varus osteotomy. Twenty-two consecutive distal femoral varus osteotomies
      converted to TKA were reviewed at a mean follow-up of 5 years (range, 2-14
      years). Stemmed femoral or tibial components were used in 5 knees with poor bone
      quality, while the remaining 17 knees were treated with unstemmed components. The
      mean Knee Society knee and function scores in surviving knees were 91 points
      (range, 67-100 points) and 64 points (range, 50-70 points) respectively at final
      follow-up. Two patients underwent revision arthroplasty for polyethylene wear and
      component loosening at 8 and 11 years after the index arthroplasty, respectively.
      Standard components provide satisfactory stability in TKA after distal femoral
      varus osteotomy after appropriate ligamentous balancing, without the need for
      stemmed or highly constrained components in the majority of patients.

PMID- 20810238
TI  - Protein C as an early biomarker to distinguish pneumonia from sepsis.
AB  - PURPOSE: Patients with pneumonia often are unrecognized as also having sepsis. We
      evaluated protein C, as a potential biomarker, to differentiate between patients
      with pneumonia and sepsis. MATERIALS AND METHODS: A retrospective chart review
      was performed for all protein C tests over a 14-month period (January 11, 2007,
      to March 10, 2008) at an 8-hospital system with 1706 total beds. Charts were
      screened for the discharge diagnoses of sepsis, severe sepsis, septic shock,
      bacteremia, and pneumonia. Protein C levels were compared between patients with
      sepsis and pneumonia, and at time intervals of 0 to 12 hours, 12 to 24 hours, 24
      to 48 hours, and more than 48 hours after diagnosis. RESULTS: One thousand forty
      seven protein C levels were obtained in 980 patients. Thirty-two protein C levels
      met the inclusion and exclusion criteria for the sepsis group, and 34 for the
      pneumonia group. Overall, the mean protein C levels were significantly less in
      patients with sepsis at 59.2% (95% confidence interval [CI], 49.5%-68.9%)
      compared with patients with pneumonia at 108.9% (95% CI, 95.6%-122.3%; P < .001).
      In addition, levels within each of the time intervals were also significantly
      lower in the sepsis group. CONCLUSIONS: In this study, protein C levels performed
      well in differentiating between patients with sepsis or pneumonia in the early
      period after diagnosis.

PMID- 20810239
TI  - The Skin Picking Impact Project: phenomenology, interference, and treatment
      utilization of pathological skin picking in a population-based sample.
AB  - The current study examined the characteristics of pathological skin picking (PSP)
      in a population-based sample. Participants were recruited through several online
      resources for PSP and related conditions to complete a web-based survey assessing
      the functional and topographical phenomenology, physical and psychosocial impact,
      treatment utilization, and associated psychopathology of PSP. A total of 1663
      participants consented, of whom 760 were over 18 and met study criteria for PSP.
      Results showed considerable heterogeneity in picking methods, body sites, and
      function (e.g., regulation of emotional, sensory, and cognitive states).
      Participants generally reported moderate psychosocial and physical impact from
      picking and tended to perceive available treatment as poor in quality. Severity
      of associated symptoms of psychopathology (depression, anxiety, and stress) was
      comparable to severity levels found in previous samples of persons with
      trichotillomania and obsessive-compulsive disorder. Severity of PSP was a
      statistically significant predictor of overall impairment after controlling for
      depression and anxiety symptoms. Results suggest that PSP is a significant public
      health concern in need of further rigorous investigation.

PMID- 20810240
TI  - Design of fuzzy cognitive maps using neural networks for predicting chaotic time
      series.
AB  - As a powerful paradigm for knowledge representation and a simulation mechanism
      applicable to numerous research and application fields, Fuzzy Cognitive Maps
      (FCMs) have attracted a great deal of attention from various research
      communities. However, the traditional FCMs do not provide efficient methods to
      determine the states of the investigated system and to quantify causalities which
      are the very foundation of the FCM theory. Therefore in many cases, constructing
      FCMs for complex causal systems greatly depends on expert knowledge. The manually
      developed models have a substantial shortcoming due to model subjectivity and
      difficulties with accessing its reliability. In this paper, we propose a fuzzy
      neural network to enhance the learning ability of FCMs so that the automatic
      determination of membership functions and quantification of causalities can be
      incorporated with the inference mechanism of conventional FCMs. In this manner,
      FCM models of the investigated systems can be automatically constructed from
      data, and therefore are independent of the experts. Furthermore, we employ mutual
      subsethood to define and describe the causalities in FCMs. It provides more
      explicit interpretation for causalities in FCMs and makes the inference process
      easier to understand. To validate the performance, the proposed approach is
      tested in predicting chaotic time series. The simulation studies show the
      effectiveness of the proposed approach.

PMID- 20810241
TI  - Takotsubo syndrome in a newborn.
AB  - Takotsubo syndrome is characterized by transient and regional left ventricular
      dysfunction, which does not correspond anatomically to coronary distribution,
      without obstructive coronary lesions and frequently follows episodes of emotional
      or physical stress. The authors present a case of takotsubo syndrome, complicated
      by acute heart failure and functional severe mitral regurgitation, in a newborn
      after fetal distress caused by the umbilical cord being twisted around the chest
      and neck. In newborns after birth asphyxia, left ventricular dysfunction has been
      reported as global and due to ischemia. In this case, the transient and regional
      left ventricular dysfunction involving segments of multiple epicardial coronary
      territories, with associated hyperkinesis of the ventricular septum and basal
      segments of other walls, could have been caused by delivery stress with
      catecholamine-mediated cardiac toxicity.

PMID- 20810242
TI  - Improvement of ultrasonic myocardial properties after aortic valve replacement
      for pure severe aortic stenosis: the predictive value of ultrasonic tissue
      characterization for left ventricle reverse remodeling.
AB  - BACKGROUND: Aortic stenosis leads to left ventricular hypertrophy and
      accumulation of fibrillar collagens. The analysis of integrated backscatter (IBS)
      parameters provides information on ultrasonic myocardial properties. METHODS: The
      study population consisted of 58 patients with aortic stenosis. They were
      followed up for an average 18 +/- 5 months after aortic valve replacement (AVR).
      Traditional transthoracic echocardiography and analysis of IBS reflectivity were
      performed before AVR and during the control visit after AVR. RESULTS: A
      significant reduction in left ventricular mass index, a significant increase in
      the mean cyclic variation of IBS, and a decrease in absolute end-diastolic IBS
      intensity were observed after AVR. CONCLUSIONS: These data suggest improvements
      in ultrasonic myocardial properties after AVR. Preoperative analysis of IBS
      parameters might provide additional information for predicting left ventricular
      reverse remodeling in patients a mean of 1.5 years after AVR for aortic stenosis.

PMID- 20810243
TI  - Global longitudinal strain as a major predictor of cardiac events in patients
      with depressed left ventricular function: a multicenter study.
AB  - BACKGROUND: The risk stratification of patients with left ventricular (LV)
      dysfunction can be performed using echocardiographic parameters such as the
      ejection fraction (EF). Recently, new technologies based on deformation
      measurements have been shown to identify early myocardial dysfunction before EF
      decrease. Consequently, tools such as two-dimensional strain have been
      incorporated into echocardiographic systems, allowing for fast, reliable, and
      reproducible calculation of longitudinal components of LV systolic deformation.
      The hypothesis in this study was that as a more sensitive marker of LV
      dysfunction, longitudinal strain would allow for the risk stratification of
      patients with heart failure. METHODS: This multicenter study included 147
      patients with heart failure with LV EFs <= 45% (mean age, 64 +/- 14 years; 74%
      men; mean LV EF, 29.9 +/- 8.9%). Conventional echocardiographic parameters as
      well as global and segmental longitudinal strain were measured and compared with
      these values in a control population. Patients were monitored for cardiac events,
      defined as a composite criterion, over 12 months. RESULTS: Clinical events were
      observed in 20% of patients during the 12-month follow-up period. On receiver
      operating characteristic curve analysis, global longitudinal strain had the
      highest prognostic value (area under the curve, 0.83) and the highest combination
      of sensitivity (73%) and specificity (83%), using a cutoff value of -7%.
      CONCLUSION: Strain assessment is highly feasible and reliable in patients with LV
      dysfunction and allows for cardiovascular risk stratification in patients with
      heart failure with greater accuracy than LV EF.

PMID- 20810244
TI  - Double-trouble Doppler: reduction in aortic flow due to combined left ventricular
      outflow tract obstruction and severe aortic stenosis, complete diagnosis by
      transthoracic Doppler echocardiography.
AB  - In patients with hypertrophic obstructive cardiomyopathy and dynamic left
      ventricular outflow tract obstructions, an additional fixed obstruction may
      uncommonly coexist. In these situations, flow through the aortic valve is usually
      delayed but typically still throughout the entire ejection period. We describe a
      case of marked reduction in aortic flow during mid and late systole, diagnosed by
      Doppler echocardiography, caused by combined hypertrophic obstructive
      cardiomyopathy and severe calcific bicuspid aortic stenosis.

PMID- 20810245
TI  - Differences of myocardial systolic deformation and correlates of diastolic
      function in competitive rowers and young hypertensives: a speckle-tracking
      echocardiography study.
AB  - BACKGROUND: The aim of this study was to compare speckle-tracking
      echocardiography-derived left ventricular (LV) systolic mechanics and their
      relationships with LV diastolic properties in young patients with hypertension
      and in young competitive athletes in relation to their respective alterations of
      LV structure. METHODS: Nineteen sedentary controls, 22 top-level rowers, and 18
      young newly diagnosed, never-treated patients with hypertension, all male,
      underwent Doppler echocardiography including pulsed tissue Doppler of the mitral
      annulus and speckle-tracking echocardiography. Peak longitudinal strain was
      calculated in apical long-axis, four-chamber, and two-chamber views, and values
      of the three views were averaged (global longitudinal strain [GLS]). Regional
      circumferential and radial strain were calculated at the LV basal, middle, and
      apical levels, and values were averaged (global circumferential strain and global
      radial strain). LV torsion was determined as the net difference in the mean
      rotation between the apical and basal levels. RESULTS: The three groups were
      comparable for age, whereas body mass index and blood pressure were higher in
      patients with hypertension, and heart rate was lower in rowers. LV mass index was
      higher in rowers and in patients with hypertension than in controls, without
      differences in relative wall thickness, ejection fraction, and midwall
      shortening. Left atrial volume index was greater in rowers than in controls and
      patients with hypertension. Annular systolic velocity (s') (P < .001) and early
      diastolic velocity (e') (P < .0001) were lower and the E/e' ratio was higher (P <
      .0001) in patients with hypertension. GLS was lower in patients with hypertension
      (-17.5 +/- 2.8%) than in rowers (-22.2 +/- 2.7%) and in controls (-21.1 +/- 2.0%)
      (P < .0001). Global circumferential strain, global radial strain, and torsion
      were similar among the three groups. In the pooled population, GLS was an
      independent contributor to E/e' ratio (P < .0001) after adjusting for age, heart
      rate, meridional end-systolic stress, LV mass index and left atrial volume index.
      By receiver operating characteristic curve analyses, both GLS and E/e' ratio
      appeared to be accurate in discriminating patients with hypertension from healthy
      controls, with the E/e' ratio being more sensitive (77.8%) and GLS more specific
      (89.5%). CONCLUSIONS: The hearts of young patients with hypertension are
      characterized by reduced GLS, whereas global circumferential strain, global
      radial strain, and torsion are similar to those of athletes' hearts. The extent
      of GLS is strongly associated with LV diastolic function, independently of
      afterload changes and the degree of LV hypertrophy.

PMID- 20810246
TI  - Aberrant expression of CD6 on B-cell subsets from patients with Sjogren's
      syndrome.
AB  - CD6 is one of a pair of related genes encoding CD5-associated receptors on all T
      cells and a subset of B cells. The current availability of "T1h", a humanized
      anti-CD6 monoclonal antibody for B cell-mediated autoimmune disorders revives
      analysis of the B-cell subset expression of CD6, particularly in primary
      Sjogren's syndrome (SS). Refined phenotype of B-lymphocytes peripheral blood
      (PB), bone marrow and tonsils revealed that the overlap between the expression of
      CD6 is less close to that of CD5 than currently acknowledged. In contrast to CD5,
      CD6 is absent on transitional B cells, while present on mature and memory B
      cells. Interestingly, the PB proportion of CD6(+) B cells is decreased in
      patients with primary SS, as opposed to those with rheumatoid arthritis. The
      reduction in primary SS does not result from the shedding of CD6 from the
      membrane of B cells, but from the lowering of memory B lymphocytes. It may result
      from the ability of CD6 to make transmigration of CD27(+) memory B cells into the
      salivary glands (SGs) easier. Consistent with this view is our finding that CD166
      (one of the ligands for CD6) is highly expressed on epithelial cells of patients'
      SGs. This study is relevant in that the humanized T1h anti-CD6 becomes an
      alternative to anti-CD20 for treatment of primary SS.

PMID- 20810247
TI  - Discrimination and variable impact of ANCA binding to different surface epitopes
      on proteinase 3, the Wegener's autoantigen.
AB  - Proteinase 3 (PR3)-specific antineutrophil cytoplasmic antibodies (ANCA) are
      highly specific for the autoimmune small vessel vasculitis, Wegener's
      granulomatosis (WG). PR3-ANCA have proven diagnostic value but their pathogenic
      potential and utility as a biomarker for disease activity remain unclear. PR3
      ANCA recognize conformational epitopes, and epitope-specific PR3-ANCA subsets
      with variable impact on biological functions of PR3 have been postulated. The
      aims of this study were to identify specific PR3 surface epitopes recognized by
      monoclonal antibodies (moAbs) and to determine whether the findings can be used
      to measure the functional impact of epitope-specific PR3-ANCA and their potential
      relationship to disease activity. We used a novel flow cytometry assay based on
      TALON-beads coated with recombinant human (H) and murine (M) PR3 and 10 custom
      designed chimeric human/mouse rPR3-variants (Hm1-5/Mh1-5) identifying 5 separate
      non-conserved PR3 surface epitopes. Anti-PR3 moAbs recognize 4 major surface
      epitopes, and we identified the specific surface location of 3 of these with the
      chimeric rPR3-variants. The ability of PR3-ANCA to inhibit the enzymatic activity
      of PR3 was measured indirectly using a capture-ELISA system based on the
      different epitopes recognized by capturing moAbs. Epitope-specific PR3-ANCA
      capture-ELISA results obtained from patient plasma (n=27) correlated with the
      inhibition of enzymatic activity of PR3 by paired IgG preparations (r=0.7,
      P<0.01). The capture-ELISA results also seem to reflect disease activity. In
      conclusion, insights about epitopes recognized by anti-PR3 moAbs can be applied
      to separate PR3-ANCA subsets with predictable functional qualities. The ability
      of PR3-ANCA to inhibit the enzymatic activity of PR3, a property linked to
      disease activity, can now be gauged using a simple epitope-based capture-ELISA
      system.

PMID- 20810248
TI  - TLR9 and TLR4 are required for the development of autoimmunity and lupus
      nephritis in pristane nephropathy.
AB  - Systemic lupus erythematosus is a common autoimmune disease, with kidney
      involvement a serious complication associated with poor prognosis. Humoral immune
      responses constitute the hallmark of disease, however T helper cells are required
      for the generation of autoantibodies, as well as the induction and progression of
      renal injury. Administration of pristane to genetically intact mice results in
      the development of hypergammaglobulinaemia with the production of lupus like
      autoantibodies and proliferative glomerulonephritis, with similarities to human
      lupus nephritis. TLRs are intricately linked to the development of autoimmunity
      and are involved in the development of lupus nephritis. We injected wild type,
      TLR9-/- and TLR4-/- mice with pristane and assessed cellular and humoral
      autoimmunity and renal injury, 8 months later. TLR9-/- mice demonstrated a
      predominant decrease in Th1 cytokine production which resulted in decreased anti
      RNP antibody levels, while anti-dsDNA levels remained intact. Compared to wild
      type mice treated with pristane, functional and histological renal injury and
      glomerular immunoglobulin and complement deposition was decreased in TLR9-/-
      mice. TLR4-/- mice demonstrated a global decrease in both Th1, IFNgamma, and Th17
      associated IL-17A and IL-6 cytokine production. Autoantibody levels of anti-dsDNA
      and anti-RNP were both decreased. Renal injury was attenuated in TLR4-/- mice
      which demonstrated less glomerular immunoglobulin and complement deposition.
      These results demonstrate that both TLR9 and TLR4 are required for 'full-blown'
      autoimmunity and organ injury in experimental lupus induced by pristane.

PMID- 20810249
TI  - Patterns of prescription of antiepileptic drugs in patients with refractory
      epilepsy at tertiary referral centres in Italy.
AB  - PURPOSE: To evaluate the pattern of prescription of antiepileptic drugs (AEDs)
      and other medications in a representative population of patients with refractory
      epilepsy attending tertiary referral centres in Italy. METHODS: Descriptive
      analysis of data obtained at baseline from 933 adults and 191 children with
      refractory epilepsy enrolled consecutively in an observational study at 11
      tertiary referral centres in Italy. Multivariate logistic regression analysis was
      used to assess predictors of utilization of the most commonly prescribed AEDs.
      RESULTS: Polytherapy was used in 79% of adults and 75% of children, with over one
      third of adults and children being prescribed >=3 AEDs. In adults, the most
      commonly used AEDs were levetiracetam (35%), carbamazepine (34%) and lamotrigine
      (30%). In children, valproic acid was by far the most commonly used AED (46%),
      followed by carbamazepine (27%), topiramate (21%), and phenobarbital (20%). The
      most common AED in partial epilepsy was carbamazepine (331 out of 893 patients,
      37%), followed by levetiracetam (33%) and lamotrigine (26%). In generalized or
      undetermined epilepsies, the AEDs most commonly used were valproic acid (139 out
      of 223 patients, 62%), lamotrigine (33%) and levetiracetam (28%). Second
      generation AEDs were prescribed in 81% of adults and 54% of children.
      Comedications used for indications other than epilepsy were used by 32% of adults
      and 17% of children. CONCLUSIONS: Prescription patterns were consistent with
      current evidence about the spectrum of efficacy of individual AEDs in different
      epilepsy syndromes. The high prevalence of polytherapy, including combinations of
      three or more AEDs, is a cause for concern.

PMID- 20810250
TI  - Association of apolipoprotein E polymorphisms with temporal lobe epilepsy in a
      Chinese Han population.
AB  - Apolipoprotein E (ApoE) has been implicated as one of the susceptibility genes
      for temporal lobe epilepsy (TLE). Previous studies indicate that ApoE E4 is
      associated with several disease-related traits including the increased risk of
      late posttraumatic seizures, earlier onset of TLE, refractory complex partial
      seizures, and postictal confusion. Contradictory data were also reported
      regarding the association between ApoE polymorphisms and TLE. The present study
      was designed to investigate whether ApoE E4 is a risk factor for TLE and the
      above clinical variables, as well as to determine whether -491A/T polymorphism
      may independently alter the risk for TLE in a Chinese Han population. The ApoE
      and -491A/T polymorphisms were genotyped in 558 controls and 735 patients
      including 560 TLE patients using polymerase chain reaction-restriction fragment
      length polymorphism. A significant association was detected between prior trauma
      and the ApoE E4 allele in TLE patients. However, no significant differences were
      observed in the genotype and haplotype distributions and allele frequencies of
      these two polymorphisms between cases and controls. Furthermore, there were no
      significant associations between these two polymorphisms and the other clinical
      variables examined. The study illustrates that the ApoE E4 allele may be involved
      in the development of TLE in those patients with prior trauma in the Chinese Han
      population.

PMID- 20810251
TI  - Statistical process control (SPC)--a simple objective method for monitoring
      seizure frequency and evaluating effectiveness of drug interventions in
      refractory childhood epilepsy.
AB  - INTRODUCTION: Objective assessment of seizure fluctuation in patients with
      refractory epilepsy in the clinical setting is difficult and subjective
      assessment may lead to inappropriate changes in medication. We therefore
      evaluated the utility of Statistical Process Control (SPC) charts as a simple
      objective clinical tool to demonstrate variability in seizure frequency and to
      assess the efficacy of drug interventions. METHODS: Total weekly seizure
      frequencies over 1 year were collected for 38 young people with refractory
      epilepsy. SPC I-charts were generated and Nelson's tests for "special" causes of
      variability applied. In a separate analysis, run charts were reviewed by two
      epileptologists blinded to clinical data who were asked to identify if and when
      drug interventions took place. RESULTS: The SPC charts showed that only seven out
      of 38 (18%) patients had stable seizure frequencies. In the others, they
      identified significant but short-lived increases in seizure frequency, which were
      followed by rapid return towards baseline independently of drug changes. A
      substantial reduction in seizure frequency was associated with a drug increase in
      only 5 (6.5%) instances. Inter-rater agreement on whether there were drug
      interventions and their timing was poor (kappa=0.15, p=0.4). CONCLUSIONS: SPC I
      charts have the potential to be used as a clinical tool to monitor seizure
      frequency and to evaluate efficacy of drug interventions in patients with
      refractory epilepsy. Epilepsy is commonly an unstable condition with fluctuations
      in seizure frequencies which are unpredictable and usually do not require a
      change in treatment. Positive responses to treatment changes are uncommon.

PMID- 20810252
TI  - Probabilistic learning and inference in schizophrenia.
AB  - Patients with schizophrenia make decisions on the basis of less evidence when
      required to collect information to make an inference, a behavior often called
      jumping to conclusions. The underlying basis for this behavior remains
      controversial. We examined the cognitive processes underpinning this finding by
      testing subjects on the beads task, which has been used previously to elicit
      jumping to conclusions behavior, and a stochastic sequence learning task, with a
      similar decision theoretic structure. During the sequence learning task, subjects
      had to learn a sequence of button presses, while receiving a noisy feedback on
      their choices. We fit a Bayesian decision making model to the sequence task and
      compared model parameters to the choice behavior in the beads task in both
      patients and healthy subjects. We found that patients did show a jumping to
      conclusions style; and those who picked early in the beads task tended to learn
      less from positive feedback in the sequence task. This favours the likelihood of
      patients selecting early because they have a low threshold for making decisions,
      and that they make choices on the basis of relatively little evidence.

PMID- 20810253
TI  - Crimean-Congo haemorrhagic fever in Eurasia.
AB  - Crimean-Congo haemorrhagic fever (CCHF) is a tick-borne infectious disease
      characterized by fever, malaise, headache, nausea, vomiting, diarrhoea, sore
      throat, muscle aches, haemorrhage and thrombocytopenia. It is a challenge for the
      population of endemic rural areas, and for healthcare workers, and carries a
      considerable mortality. The disease is widely distributed in Africa, Europe and
      Asia, and has become a serious threat to public health in Eurasia. The intention
      of this review is to summarize the current status of CCHF in Eurasia.

PMID- 20810254
TI  - Long-term effects of transference interpretation in dynamic psychotherapy of
      personality disorders.
AB  - BACKGROUND: Only a few treatment studies of personality disorders (PD) patients
      are on longer-term psychotherapy, general outcome measures are used, and follow
      up periods are usually short. More studies of long-term therapies, using outcome
      measures of core psychopathology, are needed. METHOD: This study is a dismantling
      randomized controlled clinical trial, specifically designed to study long-term
      effects of transference interpretation. Forty-six patients with mainly cluster C
      personality disorders were randomly assigned to 1 year of dynamic psychotherapy
      with or without transference interpretations. The outcome measures were remission
      from PD, improvement in interpersonal functioning, and use of mental health
      resources in the 3-year period after treatment termination. RESULTS: After
      therapy with transference interpretation PD-patients improved significantly more
      in core psychopathology and interpersonal functioning, the drop-out rate was
      reduced to zero, and use of health services was reduced to 50%, compared to
      therapy without this ingredient. Three years after treatment termination, 73% no
      longer met diagnostic criteria for any PD in the transference group, compared to
      44% in the comparison group. CONCLUSIONS: PD-patients with co-morbid disorders
      improved in both treatment arms in this study. However, transference
      interpretation improved outcome substantially more. Long-term psychotherapy that
      includes transference interpretation is an effective treatment for cluster C
      personality disorders and milder cluster B personality disorders.

PMID- 20810255
TI  - Involvement of NMDA receptors and L-arginine-nitric oxide-cyclic guanosine
      monophosphate pathway in the antidepressant-like effects of escitalopram in the
      forced swimming test.
AB  - Escitalopram is a serotonin reuptake inhibitor used in the treatment of
      depression and anxiety disorders. This study investigated the effect of
      escitalopram in forced swimming test (FST) and in the tail suspension test (TST)
      in mice, and tested the hypothesis that the inhibition of NMDA receptors and NO
      cGMP synthesis is implicated in its mechanism of action in the FST. Escitalopram
      administered by i.p. route reduced the immobility time both in the FST (0.3-10
      mg/kg) and in the TST (0.1-10 mg/kg). Administration of escitalopram by p.o route
      (0.3-10 mg/kg) also reduced the immobility time in the FST. The antidepressant
      like effect of escitalopram (3mg/kg, p.o.) in the FST was prevented by the
      pretreatment of mice with NMDA (0.1 pmol/site, i.c.v.), l-arginine (750 mg/kg,
      i.p., a substrate for nitric oxide synthase) or sildenafil (5mg/kg, i.p., a
      phosphodiesterase 5 inhibitor). The administration of 7-nitroindazole (50 mg/kg,
      i.p., a neuronal nitric oxide synthase inhibitor), methylene blue (20 mg/kg,
      i.p., an inhibitor of both nitric oxide synthase and soluble guanylate cyclase)
      or ODQ (30 pmol/site i.c.v., a soluble guanylate cyclase inhibitor) in
      combination with a subeffective dose of escitalopram (0.1 mg/kg, p.o.) reduced
      the immobility time in the FST as compared with either drug alone. None of the
      drugs produced significant effects on the locomotor activity in the open-field
      test. Altogether, our data suggest that the antidepressant-like effect of
      escitalopram is dependent on inhibition of either NMDA receptors or NO-cGMP
      synthesis. The results contribute to the understanding of the mechanisms
      underlying the antidepressant-like effect of escitalopram and reinforce the role
      of NMDA receptors and l-arginine-NO-GMP pathway in the mechanism of action of
      antidepressant agents.

PMID- 20810256
TI  - Immobilization of silver nanoparticles onto sulfonated polyethersulfone membranes
      as antibacterial materials.
AB  - By using the interaction between the sulfonated groups and silver ions, silver
      nanoparticles were successfully introduced onto the surface of sulfonated
      polyethersulfone (SPES) membranes by using vitamin C as reducing agent. The
      presence of silver nanoparticles on the surface of the PES/SPES hybrid membranes
      was characterized by UV spectrophotometer, scanning electron microscopy and
      transmission electron microscopy. Detailed studies on the antibacterial activity
      of the (PES/SPES)-Ag composites were carried out for Staphylococcus aureus,
      Staphylococcus albus, and Escherichia coli, for which, the composites exhibited
      significantly inhibition capacity. Cytocompatibility of the (PES/SPES)-Ag
      composites were also investigated by cell cytotoxicity and cell adhesion tests.
      The results indicated that after immobilizing with silver nanoparticles, the
      (PES/SPES)-Ag was still within the safe use range. To our knowledge, this is the
      first time that PES membranes have been prepared with antibacterial capacity. We
      anticipate that this novel and green method might lead to an expanded usage of
      PES with antibacterial properties in medical instruments and food processing
      industries in the future, and might also make a potential contribution to the
      fields of antibacterial chemistry.

PMID- 20810257
TI  - Management of oncological and iatrogenic urinary incontinence in malignant
      disease.
AB  - Urinary incontinence can have a major effect on quality of life, and may
      contribute to overall disability in patients with abdominal and pelvic
      malignancy. It can lead to isolation and depression, and delay rehabilitation and
      integration within family and society. With prompt assessment and correct
      management, urinary leakage can be controlled and many of the problems associated
      with urinary incontinence can be prevented to the patient's satisfaction. In
      oncological patients, this is best achieved in a multidisciplinary approach. This
      involves close co-operation between the oncologist, urologist, specialist nurses
      and individual patient, setting realistic expectations, guided by the patient's
      views and wishes. This paper reviews the management of urinary incontinence and
      its surgical treatment in the palliative setting.

PMID- 20810258
TI  - Expression and activation of matrix metalloproteinase-9 and NADPH oxidase in
      tissues and plasma of experimental autoimmune encephalomyelitis in mice.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for
      multiple sclerosis (MS) that can be induced by immunization with myelin antigens
      such as myelin oligodendrocyte glycoprotein (MOG). The objective of this study
      was (i) to investigate how matrix metalloproteinase-9 (MMP-9) and NADPH oxidase
      enzymes are affected in the EAE mouse model and (ii) to know whether peripheral
      organs also express these enzymes in the EAE model. MOG(33-55) was administered
      subcutaneously on two sites over the back. Pertussis toxin was administered
      intraperitoneally immediately after MOG and again two days later. A significant
      difference was observed in body weights and clinical signs of EAE-induced mice.
      MMP-9 and NADPH oxidase enzymes were measured in central nervous system (CNS)
      tissues, peripheral tissues and plasma of EAE-induced mice. The primary findings
      include the distribution pattern of MMP-9 in CNS and peripheral tissues, and
      alterations in the enzymatic expression of MMP-9 and NADPH oxidase in the CNS
      tissues, spleen and plasma of EAE-induced mice. From these results, it can be
      considered that the spleen as well as the CNS can act as target organs in EAE
      disease, and plasma MMP-9 and NADPH oxidase may contribute to the pathogenesis of
      the disease.

PMID- 20810259
TI  - 3D structural and functional characterization of the transition from Hodgkin to
      Reed-Sternberg cells.
AB  - Recent research using an innovative 3D quantitative FISH approach of nuclear
      remodelling associated with the transition from mononuclear Hodgkin to diagnostic
      multinuclear Reed-Sternberg cells revealed profound changes in the 3D nuclear
      organization of telomeres. Analogous 3D telomere dynamics were identified in
      Hodgkin's lymphoma derived cell-lines and diagnostic patient biopsies. These
      changes were observed in both, EBV positive and EBV-negative Hodgkin's lymphoma
      and independent of the age of the patients at presentation. Compared to
      mononuclear Hodgkin cells, multinuclear Reed-Sternberg cells are characterized by
      a highly significant increase of telomere aggregates, often composed of very
      short telomeres, telomere shortening and loss. RS-cells with telomere free
      "ghost" nuclei are regularly observed. The telomere protecting shelterin complex
      appears to be disrupted and deregulation of DNA-repair mechanisms is observed.
      Our findings are consistent with the hypothesis that distinct 3D telomere changes
      and shelterin disruption represent a common pathogenetic denominator in the
      generation of Reed-Sternberg cells.

PMID- 20810260
TI  - The role of Sp1 and Sp3 in normal and cancer cell biology.
AB  - Sp1 and Sp3 are transcription factors expressed in all mammalian cells. These
      factors are involved in regulating the transcriptional activity of genes
      implicated in most cellular processes. Dysregulation of Sp1 and Sp3 is observed
      in many cancers and diseases. Due to the amino acid sequence similarity of the
      DNA binding domains, Sp1 and Sp3 recognize and associate with the same DNA
      element with similar affinity. However, others and our laboratory demonstrated
      that these two factors possess different properties and exert different
      functional roles. Both Sp1 and Sp3 can interact with and recruit a large number
      of proteins including the transcription initiation complex, histone modifying
      enzymes and chromatin remodeling complexes, which strongly suggest that Sp1 and
      Sp3 are important transcription factors in the remodeling chromatin and the
      regulation of gene expression. In this review, the role of Sp1 and Sp3 in normal
      and cancer cell biology and the multiple mechanisms deciding the functional roles
      of Sp1 and Sp3 will be presented.

PMID- 20810261
TI  - Factors that prognosticate mortality in idiopathic pulmonary arterial
      hypertension: a systematic review of the literature.
AB  - RATIONALE: There is a lack of consensus on factors that predict mortality in
      idiopathic pulmonary arterial hypertension (IPAH). Tests that can accurately
      predict prognosis are needed to guide treatment and counsel patients. METHODS: We
      conducted a systematic review to identify factors that prognosticate mortality in
      IPAH. Study design, cohort size, comparison method, measured value, and
      statistical significance was extracted for eight pre-selected parameters
      [pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP),
      mean right atrial pressure (mRAP), cardiac output, right ventricular end
      diastolic pressure, functional class, 6 min walk distance (6MWD), and diffusing
      capacity of carbon monoxide]. RESULTS: 107 factors have been associated with
      mortality in IPAH. A reproducible predictive association with mortality was
      demonstrated for only 10 factors: functional class (14 studies), heart rate (10
      studies), 6MWD (8 studies), pericardial effusion (5 studies), mPAP (10 studies),
      mRAP (17 studies), cardiac index (13 studies), stroke volume index (4 studies),
      PVR (10 studies), mixed venous PaO(2) or saturations (4 studies). Of the 8
      factors chosen for detailed evaluation, there were at least half as many studies
      that evaluated the variable and did not find an association with mortality
      compared to those that did. CONCLUSIONS: There is a large body of literature
      describing numerous factors that predict mortality in IPAH. Most factors have
      been assessed in very few studies. There are conflicting reports on the
      prognostic value of many factors. These discrepancies highlight the need to
      evaluate the literature in total when considering the utility of variables as
      prognostic factors in IPAH.

PMID- 20810262
TI  - Behaviour and survival of high-grade neuroendocrine carcinomas of the lung.
AB  - INTRODUCTION: Large-cell neuroendocrine carcinoma is an aggressive variant of
      large-cell carcinoma of the lung, which has poor survival in most series,
      resembling that of small-cell lung carcinoma. We report our retrospective
      assessment of surgically-resected cases of both tumours. METHODS: 33 large-cell
      neuroendocrine carcinomas and 16 peripheral small-cell lung carcinomas were
      reassessed retrospectively. Survival rates of both tumours in surgically-resected
      cases were calculated and compared using Kaplan-Meier survival curves and Log
      Rank test, respectively. RESULTS: In large-cell neuroendocrine carcinomas, there
      were 25 patients with pathologic stage I, 4 with pathologic stage II and 4 with
      pathologic stage III. In small-cell lung carcinomas, there were 6 patients with
      pathologic stage I, 3 with pathologic stage II and 7 with pathologic stage III.
      12% of large-cell neuroendocrine carcinomas and 62.5% of small-cell lung
      carcinomas were of advanced disease. The mean follow-up was 89 months. The
      actuarial survival for the 2 groups was not significantly different. CONCLUSION:
      Large-cell neuroendocrine carcinomas of the lung have poor prognosis even in
      early stages, with survival rates similar to that of small-cell lung carcinomas.

PMID- 20810264
TI  - Ephrins and Eph receptors in stem cells and cancer.
AB  - Eph tyrosine kinase receptors and their ephrin ligands are expressed in most
      adult stem cell niches and in many types of tumors. They maintain tissue
      homeostasis by controlling the proliferation of stem and progenitor cells,
      although in divergent ways in different tissues. Eph receptors can also act as
      both tumor promoters and suppressors in different contexts. The recent
      characterization of the signaling pathways employed by Eph receptors has resulted
      in new suggestions for therapeutic strategies.

PMID- 20810263
TI  - Life and death in the thymus--cell death signaling during T cell development.
AB  - The thymus is an organ vital to proper T cell development, and the regulation of
      cell survival and death contributes significantly to its efficient function.
      Vital to many of the developmental processes that occur in the thymus, control
      over cell survival and death is orchestrated by several signaling processes. In
      this review, we focus on the regulation of death in early thymocytes known as
      CD4/CD8 double negative cells, including the roles of interleukin-7 and Bcl-2
      family members in this developmental stage. We next consider the survival and
      death of later thymocytes that express both CD4 and CD8, the 'double-positive'
      thymocytes. These findings are discussed within the context of recent studies
      demonstrating the existence of caspase-independent cell death pathways.

PMID- 20810265
TI  - Mechanisms of aneuploidy.
AB  - Accurate chromosome segregation during cell division is essential for genome
      integrity. Errors in chromosome segregation are irreversible and lead to a state
      of aneuploidy where the number of chromosomes in a cell or organism is not a
      multiple of the haploid number of chromosomes. Aneuploidy reduces fecundity and
      is a frequent cause of inherited birth defects. In addition, aneuploidy is very
      common in solid tumors where it is associated with poor patient prognosis. Recent
      work has revealed the most common pathways by which chromosomes mis-segregate
      leading to aneuploidy. Moreover, answers to the key question of how cells respond
      to aneuploidy are beginning to emerge.

PMID- 20810266
TI  - Turn on, tune in, but don't drop out: The impact of neo-liberalism on magic
      mushroom users' (in)ability to imagine collectivist social worlds.
AB  - BACKGROUND: Between 2002 and 2005 fresh or unprepared psilocin-based 'magic'
      mushrooms were legal to possess and traffic in the UK, and commercial sales
      demonstrated a significant market for this hallucinogenic drug. During and after
      this time there has been relatively little analysis concerning how magic mushroom
      users accounted for their drug use, nor on the wider political and cultural
      discourses that might have shaped this sense making. METHOD: In this paper we
      present a critical analysis of contemporary discourses around magic mushroom use
      in the UK through a multi-level discourse analysis of focus group data from 20
      magic mushroom users (13 male and 7 female, mean age 25 years), taken at a time
      when magic mushrooms were being legally sold in the UK. RESULTS: Locating
      participants' use of magic mushrooms within the context of a culture of
      intoxication, neo-liberalism and the legacy of 1960s psychedelic philosophy, we
      identify six interpretative repertoires in their talk, which were subsumed within
      two overarching discourses. The first discourse drew on neo-liberal rhetoric,
      constructing participants as rational risk managing subjects engaged in a form of
      calculated hedonism that was legitimated as an act of personal freedom and
      consumer choice. The second discourse, identified as 'post-psychedelic', both
      celebrated and problematised a collective, connected 'hippy' form of
      spirituality. CONCLUSION: The paper analyses the relationships between identity,
      consumption and citizenship by arguing that people's ability to imagine
      collectivist, spiritual or interconnected social worlds has been contained within
      neo-liberalism rhetoric.

PMID- 20810267
TI  - A multiplex nanoparticle-based bio-barcoded DNA sensor for the simultaneous
      detection of multiple pathogens.
AB  - A highly amplified, nanoparticle-based, bio-barcoded electrochemical biosensor
      for the simultaneous multiple detection of the protective antigen A (pagA) gene
      (accession number, M22589) of Bacillus anthracis and the insertion element (Iel)
      gene (accession number, Z83734) of Salmonella enteritidis is reported in this
      paper. The biosensor system is mainly composed of three nanoparticles: gold
      nanoparticles (AuNPs), magnetic nanoparticles (MNPs), and nanoparticle tracers
      (NTs, such as PbS and CdS). The AuNPs are coated with the first target-specific
      DNA probe (1pDNA), which can recognize one end of the target DNA sequence (tDNA),
      and many NT-terminated bio-barcode ssDNA (bDNA-NT), which act as signal reporter
      and amplifier. The MNPs are coated with the second target-specific DNA probe
      (2pDNA) that can recognize the other end of the target gene. After binding the
      nanoparticles with the target DNA, the following sandwich structure is formed:
      MNP-2pDNA/tDNA/1pDNA-AuNP-bDNA-NTs. A magnetic field is applied to separate the
      sandwich structure from the unreacted materials. Because the AuNPs have a large
      number of nanoparticle tracers per DNA probe binding event, there is substantial
      amplification. After the nanoparticle tracer is dissolved in 1M nitric acid, the
      NT(2+) ions are detected by square wave anodic stripping voltammetry (SWASV) on
      screen-printed carbon electrode (SPCE) chips. The results show that the detection
      limit of this multiplex bio-barcoded DNA sensor are 0.5 ng/mL of the insertion
      element (Iel) gene of S. enteritidis using CdS, and 50 pg/mL of the pagA gene of
      B. anthracis using PbS NTs. The nanoparticle-based bio-barcoded DNA sensor has
      potential application in rapid detection of multiple pathogenic agents in the
      same sample.

PMID- 20810268
TI  - Microfluidic monitoring of Pseudomonas aeruginosa chemotaxis under the continuous
      chemical gradient.
AB  - This study presents a microfluidic approach for the rapid analysis of bacterial
      chemotaxis in response to chemical gradients. The diffusional mixing of laminar
      flow continuously generates a stable chemical gradient in a microfluidic device.
      For the proof of concept, we have investigated the effects of the attractant
      peptone and repellent trichloroethylene (TCE) on chemotactic responses of wild
      type Pseudomonas aeruginosa PAO1 and chemotactic mutant PC4. The microfluidic
      method clearly demonstrates that P. aeruginosa PAO1 is attracted to peptone and
      repelled from TCE, whereas PC4 shows non-chemotactic behavior. In addition, the
      analysis of PAO1 chemotaxis on 20 amino acids revealed the effective
      concentration range of each amino acid as a chemoeffector. Not only does the
      microfluidic approach facilitate the quantitative information of chemotaxis,
      which gives an insight into understanding the mechanism of P. aeruginosa
      motility, but it also provides a useful tool for the rapid monitoring of
      bacterial chemotaxis in a reproducible experimental manner.

PMID- 20810269
TI  - Love-wave bacteria-based sensor for the detection of heavy metal toxicity in
      liquid medium.
AB  - The present work deals with the development of a Love-wave bacteria-based sensor
      platform for the detection of heavy metals in liquid medium. The acoustic delay
      line is inserted in an oscillation loop in order to record the resonance
      frequency in real-time. A Polydimethylsiloxane (PDMS) chip with a liquid chamber
      is maintained by pressure above the acoustic wave propagation path. Bacteria
      (Escherichia coli) were fixed as bioreceptors onto the sensitive surface of the
      sensor coated with a polyelectrolyte (PE) multilayer using a simple and efficient
      layer-by-layer (LbL) electrostatic self-assembly procedure. Poly(allylamine
      hydrochloride) (PAH cation) and poly(styrene sulfonate) (PSS anion) were
      alternatively deposited so that the strong attraction between oppositely charged
      polyelectrolytes resulted in the formation of a (PAH-PSS)(n)-PAH molecular
      multilayer. The real-time characterization of PE multilayer and bacteria
      deposition is based on the measurement of the resonance frequency perturbation
      due to mass loading during material deposition. Real-time response to various
      concentrations of cadmium (Cd(2+)) and mercury (Hg(2+)) has been investigated. A
      detection limit as low as 10(-12) mol/l has been achieved, above which the
      frequency increases gradually up to 10(-3) mol/l, after a delay of 60 s
      subsequent to their introduction onto bacterial cell-based biosensors. Beyond a
      10(-3) mol/l a steep drop in frequency was observed. This response has been
      attributed to changes in viscoelastic properties, related to modifications in
      bacteria metabolism.

PMID- 20810270
TI  - Biochemical gas sensor (bio-sniffer) for ultrahigh-sensitive gaseous formaldehyde
      monitoring.
AB  - An ultrahigh-sensitive fiber-optic biochemical gas sensor (bio-sniffer) for
      continuous monitoring of indoor formaldehyde was constructed and tested. The bio
      sniffer measures gaseous formaldehyde as fluorescence of nicotinamide adenine
      dinucleotide (NADH), which is the product of formaldehyde dehydrogenase (FALDH)
      reaction. The bio-sniffer device was constructed by attaching a flow cell with a
      FALDH immobilized membrane onto a fiber-optic NADH measurement system. The NADH
      measurement system utilizes an ultraviolet-light emitting diode (UV-LED) with
      peak emission of 335 nm as an excitation light source. The excitation light was
      introduced to an optical fiber probe, and fluorescence emission of neighboring
      NADH, which was produced by applying formaldehyde vapor to the FALDH membrane,
      was concentrically measured with a photomultiplier tube. Assessment of the bio
      sniffer was carried out using a standard gas generator. Response, calibration
      range and selectivity to other chemical substances were investigated. Circulating
      phosphate buffer, which contained NAD+, available for continuous monitoring of
      formaldehyde vapor. The calibration range of the bio-sniffer was 2.5 ppb to 10
      ppm, which covers the guideline value of the World Health Organization (80 ppb).
      High selectivity to other gaseous substances due to specific activity of FALDH
      was also confirmed. Considering its high sensitivity, a possible application of
      the bio-sniffer is continuous indoor formaldehyde monitoring to provide healthy
      residential atmosphere.

PMID- 20810271
TI  - Nanoliter contact angle probes tumor angiogenic ligand-receptor protein
      interactions.
AB  - Any molecular recognition reaction supported by a solid phase drives a specific
      change of the solid-solution interfacial tension. Sessile contact angle (CA)
      experiments can be readily used to track this thermodynamic parameter, prompting
      this well-known technique to be reinvented as an alternative, easy-access and
      label-free way to probe and study molecular recognition events. Here we deploy
      this technique, renamed for this application CONAMORE (CONtact Angle MOlecular
      REcognition), to study the interaction of the tumor-derived pro-angiogenic
      vascular endothelial growth factor-A (VEGF-A) with the extracellular domain of
      its receptor VEGFR2. We show that CONAMORE recognizes the high affinity binding
      of VEGF-A at nanomolar concentrations to surface-immobilized VEGFR2 regardless of
      the presence of a ten-fold excess of a non-specific interacting protein, and that
      it further proofs its specificity and reliability on competitive binding
      experiments involving neutralizing anti-VEGF-A antibodies. Finally, CONAMORE
      shows the outstanding capability to detect the specific interaction between
      VEGFR2 and low molecular weight ligands, such as Cyclo-VEGI, a VEGFR2 antagonist
      cyclo-peptide, that weighs about 2 kDa.

PMID- 20810272
TI  - Electrospun Co3O4 nanofibers for sensitive and selective glucose detection.
AB  - Co3O4 nanofibers were fabricated by a two-step procedure consisting of
      electrospinning and subsequent calcination. Scanning electron microscopy and
      transmission electron microscopy were employed to characterize the as-prepared
      Co3O4 nanofibers. Fourier transform infrared spectroscopy and Raman spectroscopy
      were used to confirm the degradation of the polymer matrix and the complete
      conversion of cobalt nitrate to cobalt oxide. Furthermore, the composition and
      crystal structure of the final product were investigated using X-ray diffraction
      and X-ray photoelectron spectroscopy. The as-prepared Co3O4 nanofibers were
      applied to construct a non-enzymatic sensor for glucose detection in alkaline
      solution. The developed sensor showed a fast response time (less than 7 s), a
      high sensitivity of 36.25 MUA mM(-1) cm(-2), good reproducibility and
      selectivity, and a detection limit of 0.97 MUM (S/N=3). The high concentration of
      NaCl does not poison the electrode. Its application for the detection of glucose
      in human blood serum sample shows good agreement with the results obtained from
      commercial glucose meter. The Langmuir isothermal theory was employed to fit the
      obtained calibration curve. The mechanisms for the glucose oxidation promoted by
      Co3O4 nanofibers and the good selectivity against uric acid and ascorbic acid at
      an applied potential of +0.59 V vs. Ag/AgCl were also proposed. These results
      demonstrate that Co3O4 nanofibers have great potential applications in the
      development of sensors for enzyme-free detection of glucose.

PMID- 20810273
TI  - Double recognition of oligonucleotide and protein in the detection of DNA
      methylation with surface plasmon resonance biosensors.
AB  - DNA methylation plays an essential role in maintenance of cellular function. A
      growing number of human diseases have been found to be associated with aberrant
      DNA methylation, especially cancer. However, current technologies used in DNA
      methylation detection are complicated and time consuming. A promotor of the
      Adenomatous polyposis coli (APC) gene, a well-studied tumor suppressor gene, was
      used as the detection target DNA sequence. The double recognition mechanism was
      realized with oligonucleotide probe hybridization and specific protein binding.
      First, complementary target DNA was captured by the probe immobilized onto a
      surface plasmon resonance (SPR) sensor chip. Then, the recombinant methyl-CpG
      binding domain (MBD) protein was passed over the surface to recognize and bind to
      methylated CpG sites. Binding resulted in an increase in the refractive index,
      and a detectable optical signal was generated. Five picomoles of methylated APC
      promotor DNA could be easily detected with this method. The entire detection
      could be completed within 1h. This work represents the first SPR based biosensor
      technology, which achieves simple and specific DNA methylation detection and
      avoids complicated bisulfite treatment and methylation-sensitive restriction
      digestion. It will improve our ability to detect DNA methylation specifically and
      rapidly, and promote our understanding of the role of DNA methylation in gene
      regulation and diseases.

PMID- 20810274
TI  - Nanobiotechnology.

PMID- 20810275
TI  - Oscillatory dynamics of the extracellular signal-regulated kinase pathway.
AB  - The extracellular signal-regulated kinase (ERK) pathway is a central signaling
      pathway in development and disease and is regulated by multiple negative and
      positive feedback loops. Recent studies have shown negative feedback from ERK to
      upstream regulators can give rise to biochemical oscillations with a periodicity
      of between 15 and 30min. Feedback due to the stimulated transcription of negative
      regulators of the ERK pathway can also give rise to transcriptional oscillations
      with a periodicity of one to two hours. The biological significance of these
      oscillations is not clear, but recent evidence suggests that transcriptional
      oscillations participate in developmental processes, such as somite formation.
      Biochemical oscillations are more enigmatic, but could provide a mechanism for
      encoding different types of inputs into a common signaling pathway.

PMID- 20810276
TI  - Retrograde neural circuit specification by target-derived neurotrophins and
      growth factors.
AB  - Neural circuit assembly during development involves a series of highly regulated
      steps. While genetically pre-determined programs play key roles in the early
      steps including neurogenesis, migration, and initial growth and guidance of
      axons; increasing evidence indicates that as the axons reach their targets, the
      late steps of neuronal differentiation and connectivity formation may be
      influenced or even specified by target-derived signals. Here we attempt to
      provide a brief synthesized review on the roles of retrograde neurotrophin and
      growth factor signaling in regulating the final stages of neural circuit
      specificity such as axonal projection, dendritic patterning, neurotransmitter
      phenotype acquisition, and synapse formation.

PMID- 20810278
TI  - Resolution of racemic sulfoxides with high productivity and enantioselectivity by
      a Rhodococcus sp. strain as an alternative to biooxidation of prochiral sulfides
      for efficient production of enantiopure sulfoxides.
AB  - Whole cells of Rhodococcus sp. ECU0066 were used a catalyst for resolution of
      racemic sulfoxides, as an alternative to asymmetric oxidation of sulfides for
      efficient production of enantiopure sulfoxides. Racemic sulfoxides were excellent
      substrates for biotransformation because of their lower biotoxicity compared to
      sulfides. Determination of apparent kinetic parameters indicated that phenyl
      methyl sulfide (PMS), but not racemic phenyl methyl sulfoxide (rac-PMSO) caused
      substrate inhibition. (S)-PMSO was formed at a higher concentration and good
      enantiomeric excess (37.8 mM and 93.7% ee(S)) in a fed-batch reaction, than by an
      asymmetric oxidation of PMS (10 mM and 80% eeP (S)). The bacterium also displayed
      fairly good activity (yields, 22.7-43.2%; within 1-8 h) and enantioselectivity
      (ee(S)>99.0%) towards para-substituted (methyl and chloro) phenyl methyl
      sulfoxides and ethyl phenyl sulfoxide, indicating it could be a promising agent
      for synthetic applications.

PMID- 20810277
TI  - Unmet challenges of structural genomics.
AB  - Structural genomics (SG) programs have developed during the last decade many
      novel methodologies for faster and more accurate structure determination. These
      new tools and approaches led to the determination of thousands of protein
      structures. The generation of enormous amounts of experimental data resulted in
      significant improvements in the understanding of many biological processes at
      molecular levels. However, the amount of data collected so far is so large that
      traditional analysis methods are limiting the rate of extraction of biological
      and biochemical information from 3D models. This situation has prompted us to
      review the challenges that remain unmet by SG, as well as the areas in which the
      potential impact of SG could exceed what has been achieved so far.

PMID- 20810279
TI  - Discovery of pyrrolopyrimidine inhibitors of Akt.
AB  - The discovery and optimization of a series of pyrrolopyrimidine based protein
      kinase B (Pkb/Akt) inhibitors discovered via HTS and structure based drug design
      is reported. The compounds demonstrate potent inhibition of all three Akt
      isoforms and knockdown of phospho-PRAS40 levels in LNCaP cells and tumor
      xenografts.

PMID- 20810280
TI  - Novel pyrimidines as acid pump antagonists (APAs).
AB  - A series of pyrimidine derivatives as acid pump antagonists (APAs) was
      synthesized and the inhibitory activities against H(+)/K(+) ATPase isolated from
      hog gastric mucosa were determined. After elaborating on substituents at C2 and
      C4 position of the pyrimidine scaffold, we have observed that the compound 7h is
      a potent APA with H(+)/K(+) ATPase, IC(50) = 52 nM.

PMID- 20810281
TI  - Not waiting to live, not living to wait....

PMID- 20810282
TI  - Different prognostic significance of CD24 and CD44 expression in breast cancer
      according to hormone receptor status.
AB  - OBJECTIVE: CD44(+)CD24(-/low)-expressing tumor cells have been studied as
      tumorigenic stem cells in vitro study. This study was designed to determine the
      clinical implication of the CD44 and CD24 expression in breast cancer. METHODS:
      Tissue microarray blocks containing 643 consecutive cases of invasive breast
      carcinomas from 1993 to 1998 were immunostained for CD44 and CD24. The median
      follow-up period was 127 months. RESULTS: CD44(-)CD24(+) phenotype was associated
      with frequent hormone receptor positivity and Her2/neu positivity (P = 0.000;
      Both). The CD44(+)CD24(-) phenotype was inversely associated with lymph node
      metastasis (P = 0.002), and it showed positive associations with prolonged
      disease-free survival (DFS; P = 0.003) and overall survival (OS; P = 0.002). 10
      year DFS and OS were 68.9% and 74.6% for CD24 negative group, 55.6% and 60.9% for
      CD24 positive group (P = 0.001; Both). 10-year DFS and OS were 62.2% and 68.1%
      for CD44 negative group, 73% and 77.7% for CD44 positive group (P = 0.012, P =
      0.013, respectively). In a multivariate analysis, CD24 expression was negatively
      related to OS only in the receptor positive group (Hazard ratio = 2.03; P =
      0.003; 95% CI: 1.27-3.24) and CD44 expression was positively related to OS only
      in the hormone receptor negative group (hazard ratio = 0.58; P = 0.022; 95% CI:
      0.36-0.92). CONCLUSIONS: The CD44(+)CD24(-) group is considered a favorable
      prognostic subgroup in breast cancer. CD24 expression was a poor prognosis marker
      in hormone receptor positive breast cancer, and CD44 expression was a good
      prognostic marker in the receptor negative group.

PMID- 20810284
TI  - Decoding cytosolic Ca2+ oscillations.
AB  - A rise in cytosolic Ca(2+) concentration is used as a universal signalling
      mechanism to control biological processes as diverse as exocytosis, contraction,
      cell growth and cell death. Ca(2+) signals are often presented to cells in the
      form of Ca(2+) oscillations, with signalling information encoded in both
      amplitude and frequency of the Ca(2+) spikes. Recent studies have revealed that
      the sub-cellular spatial profile of the Ca(2+) oscillation is also important in
      activating cellular responses, thereby suggesting a new mechanism for extracting
      information from the ubiquitous Ca(2+) oscillation.

PMID- 20810283
TI  - DNA methylation and cellular reprogramming.
AB  - The recent discovery that a small number of defined factors are sufficient to
      reprogram somatic cells into pluripotent stem cells has significantly expanded
      our knowledge of the plasticity of the epigenome. In this review we discuss some
      aspects of cell fate plasticity and epigenetic alterations, with emphasis on DNA
      methylation during cellular reprogramming. Recent data suggest that DNA
      methylation is a major barrier to induced pluripotent stem (iPS) cell
      reprogramming. The demethylating agent 5-azacytidine can enhance the efficiency
      of iPS cells generation and the putative DNA demethylase protein activation
      induced cytidine deaminase (AID/AICDA) can erase DNA methylation at pluripotency
      gene promoters, thereby allowing cellular reprogramming. Elucidation of the
      epigenetic changes taking place during cellular reprogramming will enhance our
      understanding of stem cell biology and facilitate therapeutic applications.

PMID- 20810285
TI  - Structure-based virtual screening of novel tubulin inhibitors and their
      characterization as anti-mitotic agents.
AB  - Microtubule cytoskeletons are involved in many essential functions throughout the
      life cycle of cells, including transport of materials into cells, cell movement,
      and proper progression of cell division. Small compounds that can bind at the
      colchicine site of tubulin have drawn great attention because these agents can
      suppress or inhibit microtubule dynamics and tubulin polymerization. To find
      novel tubulin polymerization inhibitors as anti-mitotic agents, we performed a
      virtual screening study of the colchicine binding site on tubulin. Novel tubulin
      inhibitors were identified and characterized by their inhibitory activities on
      tubulin polymerization in vitro. The structural basis for the interaction of
      novel inhibitors with tubulin was investigated by molecular modeling, and we have
      proposed binding models for these hit compounds with tubulin. The proposed
      docking models were very similar to the binding pattern of colchicine or
      podophyllotoxin with tubulin. These new hit compound derivatives exerted growth
      inhibitory effects on the HL60 cell lines tested and exhibited strong cell cycle
      arrest at G2/M phase. Furthermore, these compounds induced apoptosis after cell
      cycle arrest. In this study, we show that the validated derivatives of compound
      11 could serve as potent lead compounds for designing novel anti-cancer agents
      that target microtubules.

PMID- 20810286
TI  - QSAR-based solubility model for drug-like compounds.
AB  - Solubility plays a very important role in the selection of compounds for drug
      screening. In this context, a QSAR model was developed for predicting water
      solubility of drug-like compounds. First, a set of relevant parameters for
      establishing a drug-like chemical space was defined. The comparison of chemical
      structures from the FDAMDD and PHYSPROP databases allowed the selection of
      properties that were more efficient in discriminating drug-like compounds from
      other chemicals. These filters were later on applied to the PHYSPROP database and
      1174 chemicals fulfilling these criteria and with experimental solubility
      information available at 25 degrees C were retained. Several QSAR solubility
      models were developed from this set of compounds, and the best one was selected
      based on the accuracy of correct classifications obtained for randomly chosen
      training and validation subsets. Further validation of the model was performed
      with a set of 102 drugs for which experimental solubility data have been recently
      reported. A good agreement between the predictions and the experimental values
      confirmed the reliability of the QSAR model.

PMID- 20810287
TI  - Molecular scale track structure simulations in liquid water using the Geant4-DNA
      Monte-Carlo processes.
AB  - This paper presents a study of energy deposits induced by ionising particles in
      liquid water at the molecular scale. Particles track structures were generated
      using the Geant4-DNA processes of the Geant4 Monte-Carlo toolkit. These processes
      cover electrons (0.025 eV-1 MeV), protons (1 keV-100 MeV), hydrogen atoms (1 keV
      100 MeV) and alpha particles (10 keV-40 MeV) including their different charge
      states. Electron ranges and lineal energies for protons were calculated in
      nanometric and micrometric volumes.

PMID- 20810288
TI  - The primordium of a biological joint replacement: Coupling of two stem cell
      pathways in biphasic ultrarapid compressed gel niches.
AB  - The impaired temporomandibular joint might be the first to benefit from applied
      tissue engineering techniques because it is small and tissue growth in larger
      amounts is challenging. Bone and cartilage require different competing
      environmental conditions to be cultivated in vitro. But coupling both the
      osteogenic and cartilaginous pathways of mesenchymal stem cell differentiation in
      homeostasis will be a key essential to grow osteochondral constructs or even the
      first biological joint replacement in the future. The aim of this study was to
      test a single source biomaterial and a single source cell type to engineer a
      biphasic osteochondral construct in vitro for future in vivo implantation.
      Ultrarapid tissue engineering techniques were used to create the biphasic matrix
      and primary human mesenchymal stem cells (MSCs) preconditioned in osteogenic and
      chondrogenic media were then seeded in opposite portions of the hyper-hydrated
      collagen gel in order to further substantiate the respective bone-like and
      cartilage-like layers thus potentially customising the collagen scaffold
      according to patient needs in regards to future biological joint replacements.
      After incubation for 7 days to allow cell growth and differentiation,
      mineralization of the bone-like layer was demonstrated using von Kossa staining
      and biochemical bone markers. The cartilage-like layer was demonstrated using
      alcian blue staining and biochemical cartilage markers. Integration of the bone
      like and cartilage-like layers to simulate a tidemark layer was achieved through
      partial setting of the gels. Cell tracking was used to further confirm the
      establishment of distinct cartilage-like and bone-like areas within the single
      construct. This is the first report of one homogeneous human MSC population
      differentiating into dissimilar "bone-like" and "cartilage-like" zones hosted in
      a biphasic ultrarapid compressed gel phase niche and mimicking a primordial joint
      like structure.

PMID- 20810289
TI  - Treatment for advanced cervical cancer: impact on quality of life.
AB  - Cisplatin-based combinations can potentially improve response rates in patients
      with cervical cancer, but unacceptable toxicity must be avoided. Quality of life
      (QoL) measures are increasingly used to assess the benefits versus limitations of
      chemotherapy regimens. A MEDLINE search of English language publications from
      January 2000 to December 2008 was conducted using the search terms: 'quality of
      life' OR 'QoL' OR 'HRQoL' AND 'cervical cancer'. Abstracts from the Association
      of Clinical Oncology meeting, 2008, were also searched. Article inclusion was
      based on abstract content. Several cervical cancer therapies have shown response
      rate improvements in combination with cisplatin, including topotecan and
      paclitaxel. However, only topotecan/cisplatin demonstrates a significant overall
      survival advantage over cisplatin monotherapy, while both topotecan/cisplatin and
      paclitaxel/cisplatin demonstrate comparable impact on QoL to cisplatin alone. Few
      trials of combination chemotherapy for cervical cancer have directly assessed
      QoL. The combination of topotecan/cisplatin significantly increases overall
      survival rates without reducing patient QoL.

PMID- 20810290
TI  - Experimental evaluation of inhibitory effect of 10-hydroxycamptothecin on hypoxia
      inducible factor-1alpha expression and angiogenesis in liver tumors after
      transcatheter arterial embolization.
AB  - PURPOSE: To evaluate the effect of transcatheter administration of 10
      hydroxycamptothecin (HCPT), a hypoxia-inducible factor-1alpha (HIF-1alpha)
      inhibitor, on HIF-1alpha expression and angiogenesis in liver tumors after
      transcatheter arterial embolization in an animal model. MATERIALS AND METHODS:
      VX2 tumors were implanted in the livers of 30 rabbits. The animals were divided
      randomly into three groups of 10 animals each. Group 1 animals received hepatic
      intraarterial infusion of distilled water. Group 2 animals received iodized oil
      infusion followed by embolization with 150-250 MUm of polyvinyl alcohol
      particles. Group 3 animals received infusion of a mixture of HCPT (1 mg/kg body
      weight) with iodized oil followed by the particle embolization. Six hours or 3
      days after transcatheter treatment, the animals were sacrificed, and the tumor
      samples were harvested. Immunohistochemical staining was performed to evaluate
      the levels of HIF-1alpha and vascular endothelial growth factor (VEGF) protein as
      well as microvessel density. RESULTS: The levels of HIF-1alpha and VEGF and
      microvessel density in tumors of group 2 were significantly higher than those of
      group 1 or 3 (P < .05). However, no significant differences were noted in tumors
      between group 1 and 3 (P > .05). HIF-1alpha levels were significantly correlated
      with VEGF levels (r = .587, P = .001) and microvessel density (r = .527, P =
      .003). CONCLUSIONS: Transcatheter infusion of HCPT has an inhibitory effect on
      HIF-1alpha expression and angiogenesis in liver tumors after transcatheter
      arterial embolization.

PMID- 20810291
TI  - Focal articular cartilage defect treated by percutaneous radiofrequency ablation.
AB  - A 30-year-old man presented with a painful intraarticular lesion in the knee,
      clinically simulating osteoid osteoma. Pretherapeutic imaging disclosed a focal
      articular cartilage defect located in the medial femoral condyle and surrounded
      by extensive bone marrow edema. The defect was inaccessible for arthroscopic
      treatment because of its unusual posterosuperior location. Percutaneous
      radiofrequency ablation was then performed under computed tomography guidance,
      resulting in complete resolution of symptoms. Magnetic resonance imaging follow
      up found resolution of the bone marrow edema pattern around the lesion and growth
      of fat in the site of the previous lesion.

PMID- 20810292
TI  - On solid-phase antibody assays.
AB  - There is considerable evidence that pre-operative and post-operative anti-human
      leukocyte antigen (anti-HLA) antibodies are deleterious in thoracic
      transplantation. While debate continues in heart and lung transplantation on the
      role of and the diagnosis and treatment of antibody-mediated rejection (AMR),
      central to the discussion is our ability to detect anti-HLA antibodies. This
      perspective outlines the concerns elicited by new technology for detection of
      anti-HLA antibodies using solid-phase assays, and highlights the need for
      functional assays to further understand the clinical significance of these
      antibodies.

PMID- 20810293
TI  - Lung transplantation for patients with cystic fibrosis and Burkholderia cepacia
      complex infection: a single-center experience.
AB  - BACKGROUND: Pre-operative infection with organisms from the Burkholderia cepacia
      complex (BCC), particularly B cenocepacia, has been linked with a poorer
      prognosis after transplantation compared to patients with cystic fibrosis (CF)
      without this infection. Therefore, many transplant centers do not list these
      patients for transplantation. METHODS: We report the early and long-term results
      of a cohort of lung transplant recipients with CF and pre-operative BCC
      infection. Patients with pre-transplantation BCC infection were identified by
      case-note review. BCC species status was assigned by polymerase chain reaction
      (PCR)-based techniques. Survival rates were compared to recipients with CF
      without BCC infection. Survival rates in BCC subgroups were also compared, and
      then further analyzed pre- and post-2001, when a new immunosuppressive and
      antibiotic regime was introduced for such patients. RESULTS: Two hundred sixteen
      patients with CF underwent lung transplantation and 22 had confirmed pre
      operative BCC infection, with 12 of these being B cenocepacia. Nine B cenocepacia
      infected recipients died within the first year, and in 8 BCC sepsis was
      considered to be the cause of death. Despite instituting a tailored peri
      operative immunosuppressive and microbiologic care approach for such patients,
      post-transplantation BCC septic deaths occurred frequently in those with pre
      transplantation B cenocepacia infection. In contrast, recipients infected with
      other BCC species had significantly better outcomes, with post-transplantation
      survival comparable to other recipients with CF. CONCLUSIONS: Mortality in
      patients with B cenocepacia infection was unacceptably high and has led to our
      center no longer accepting patients with this condition onto the lung transplant
      waiting list. Long-term survival in the non-B cenocepacia BCC group was
      excellent, without high rates of acute rejection or bronchiolitis obliterans
      syndrome (BOS) longer term, and these patients continue to be considered for lung
      transplantation.

PMID- 20810294
TI  - The use of an acoustic device to identify the epidural space in cattle.
AB  - Twelve healthy cattle (weighing 188-835 kg) were placed in stocks and sedated
      with xylazine. Caudal epidural puncture was performed using an acoustic device
      that indicated a decrease in resistance with a change in pitch. Lidocaine was
      injected to verify correct needle placement by assessing needle prick stimuli
      applied on the left and right side of the tail root and the perineal region, and
      the loss of tail and anal sphincter tone. Pressure measurements were recorded
      during penetration of the different tissue layers and in the epidural space. A
      clear and sudden decrease in the pitch of the acoustic signal was audible in all
      12 cattle. All cows showed clinical effects indicating successful epidural
      anaesthesia. The pressure in the epidural space after puncture was -19+/-10 mm
      Hg. The device may be of assistance in identifying the epidural space in cattle.

PMID- 20810295
TI  - Contrast-enhanced dynamic magnetic resonance nephrography in healthy dogs.
AB  - Twenty-three healthy mixed-breed male adult dogs were examined using serial
      magnetic resonance (MR) renograms. The images were obtained using a dynamic
      gradient-echo, fast SPGR, T1-weighted sequence and low doses of gadolinium
      chelates (0.025 mmol/kg). Time-intensity curves were obtained to assess typical
      urinary excretion parameters, namely, time to vascular peak (TVP), time to
      vascular drop (TVD), time to glomerular peak (TGP), parenchymal phase length
      (PPL), gradient of parenchymal phase (GPP) and pattern of excretory segment. The
      mean TVP, TVD, TGP and PPL were 31.6+/-11.8, 43.4+/-11.2, 154.0+/-36.2 and
      115.2+/-37.7s, respectively. The GPP was 24.1+/-8.6% of signal intensity per min.
      The excretory segment was concave in all cases, and at the end of the
      examination, 87.1% of kidneys had shown a reduction in signal intensity of 50%.
      This MR nephrography protocol can provide adequate time-intensity curve
      parameters for the urinary system of dogs, offers excellent anatomical detail,
      and represents an alternative to radionuclide nephrography.

PMID- 20810296
TI  - Acute infantile encephalopathy predominantly affecting the frontal lobe (AIEF): a
      European case.
AB  - Acute infantile encephalopathy predominantly affecting the frontal lobes (AIEF)
      has been described as a new entity, based on MRI findings (acute abnormal
      diffusion-weighted imaging signals in the frontal lobes followed by atrophy) and
      exclusion of other acute encephalopathies. Patients present with acute onset of
      fever, status epilepticus, and coma. Different causal mechanisms have been
      suggested such as localized viral infection, toxic insult due to cytokines, or
      postictal damage. Only children of Japanese descent have been described. We
      report the case of a Caucasian girl whose history and MRI findings were similar
      to the Japanese cases. She had a massive regression with verbal apraxia, while
      cognitive development was less affected; she initially presented with a cluster
      of complex partial seizures (and not convulsive status epilepticus), making
      epileptic or post anoxic-ischemic sequelae highly unlikely. The place of this
      proposed entity among other recently described acute encephalopathies with
      abnormal diffusion on MRI is discussed.

PMID- 20810297
TI  - Posterior reversible encephalopathy syndrome during leukaemia chemotherapy.

PMID- 20810299
TI  - [Reirradiation of head and neck cancers].
AB  - Locally advanced head and neck cancers are primarily treated by a multimodal
      approach, including a combination of surgery, radiotherapy and chemotherapy.
      However, local relapse rate in a previously irradiated area remains high.
      Reirradiation for a nonoperable recurrence or a new primary tumour is now a
      therapeutic option thanks to technical progresses. This review presents results
      of published series in terms of toxicity and tumour response. All the
      publications are heterogeneous (population, dose, fractionation, concomitant
      chemotherapy or targeted therapy) and it is thus difficult to compare results.
      Reirradiation is feasible and appears less toxic with new techniques such as
      image guided radiotherapy (IMRT) or stereotactic radiotherapy, which could offer
      precise radiation delivery while sparing healthy tissues. Concomitant
      chemotherapy or targeted therapy may improve local control. Prospective
      evaluation of tumour response and complications is necessary.

PMID- 20810298
TI  - Characterization of imaging gradients in diffusion tensor imaging.
AB  - For obtaining a complete model the diffusion tensor imaging (DTI) method is
      derived in a new linear algebraic framework in order to include the effect of all
      of the magnetic field gradients on the MRI signal. In the framework, the
      coefficient matrix of the estimation equations consists of the sum of three
      matrices corresponding to diffusion gradients, imaging gradients and the cross
      terms between them. The derivations demonstrate that there exists modeling
      incongruities originating from the choice of phase-encoding gradient magnitude
      and the read-out gradient affecting the entirety of the signal sample points.
      These reflect on the cross-terms and the imaging gradient coefficient matrix,
      revealing the DTI's inadequacy for the inclusion of imaging gradients. The linear
      algebraic framework mitigates the inadequacy by the utilization of center
      symmetric gradient schemes. The observations are verified by the experimental
      results obtained from an isotropic phantom using several existing diffusion
      gradient schemes.

PMID- 20810300
TI  - [Postoperative radiotherapy of prostate cancer].
AB  - After radical prostatectomy, the risk of biological recurrence at 5 years varies
      from 10 to 40 % and this natural evolution of the disease has led radiation
      therapy being proposed as a supplement to surgery. When the recurrence risk is
      essentially local, supplementary radiotherapy is justified in the aim of
      improving biological recurrence-free survival, local control, metastasis-free
      survival and specific and global survival, while respecting patient quality of
      life. Three recent studies, EORTC 22911, ARO 9602 and SWOG 8794 found a similar
      advantage for biological recurrence-free survival without higher major additional
      toxicity. However, only the SWOG 8794 study found a significant improvement for
      metastasis-free survival and global survival. In an adjuvant setting, the optimal
      moment to propose this postoperative radiotherapy remains uncertain: should it be
      proposed systematically to all pT3 R1 patients, running the risk of pointlessly
      treating patients who will never recur, or should it only be proposed at
      recurrence? The GETUG AFU 17 trial will provide answers to the question of the
      optimal moment for postoperative radiotherapy for pT3-4 R1 pN0 Nx patients with
      the objective of comparing an immediate treatment to a differed early treatment
      initiated at biological recurrence.

PMID- 20810301
TI  - Utilizing spatiotemporal analysis of influenza-like illness and rapid tests to
      focus swine-origin influenza virus intervention.
AB  - In the spring of 2009, a novel strain of H1N1 swine-origin influenza A virus (S
      OIV) emerged in Mexico and the United States, and soon after was declared a
      pandemic by the World Health Organization. This work examined the ability of real
      time reports of influenza-like illness (ILI) symptoms and rapid influenza
      diagnostic tests (RIDTs) to approximate the spatiotemporal distribution of PCR
      confirmed S-OIV cases for the purposes of focusing local intervention efforts.
      Cluster and age adjusted relative risk patterns of ILI, RIDT, and S-OIV were
      assessed at a fine spatial scale at different time and space extents within
      Cameron County, Texas on the US-Mexico border. Space-time patterns of ILI and
      RIDT were found to effectively characterize the areas with highest geographical
      risk of S-OIV within the first two weeks of the outbreak. Based on these results,
      ILI and/or RIDT may prove to be acceptable indicators of the location of S-OIV
      hotspots. Given that S-OIV data is often difficult to obtain real-time during an
      outbreak; these findings may be of use to public health officials targeting
      prevention and response efforts during future flu outbreaks.

PMID- 20810302
TI  - Normal response to Upper Limb Neurodynamic Test 1 and 2A.

PMID- 20810303
TI  - Interexaminer reliability of orthopaedic special tests used in the assessment of
      shoulder pain.
AB  - Orthopaedic special tests (OST) are commonly used in the assessment of the
      painful shoulder to assist to rule-in or rule-out specific pathology. A small
      number of tests with high levels of diagnostic accuracy have been identified but
      interexaminer reliability data is variable or lacking. The aim of this study was
      to determine the interexaminer reliability of a group of OST with demonstrated
      diagnostic accuracy at primary care level. Forty consecutive subjects with
      shoulder pain were recruited. Six tests were performed by two examiners
      (physiotherapists) on the same day. Tests included the active compression test,
      Hawkins-Kennedy test, drop-arm test, crank test, Kim test and belly-press test.
      'Fair' reliability (kappa 0.36-0.38) was observed for the active compression test
      (labral pathology), Hawkins-Kennedy test and crank test. Prevalence of positive
      agreements was low for the active compression test (acromioclavicular joint),
      drop-arm test, Kim test and belly-press test. Prevalence and bias adjusted kappa
      (PABAK) values indicated 'substantial' reliability (0.65-0.78) for these tests.
      The active compression test (acromioclavicular joint), belly-press tests
      (observation and weakness), Kim test and drop-arm test demonstrate acceptable
      levels of interexaminer reliability in a group of patients with sub-acute and
      chronic shoulder conditions.

PMID- 20810304
TI  - Enzyme catalysis from improved packing in their transition-state structures.
AB  - The binding of ligands to proteins can be enhanced through improved packing
      within the proteins that may, or may not, occur with conformational change.
      Enzymes can similarly improve their catalytic magic through better packing in the
      transition state (TS) for reaction. In principle, the improved packing demands no
      more than the minute shortening of non-covalent interactions throughout much of
      the structure of the protein (positively cooperative binding). Improved protein
      packing can account for the remarkably high biotin/streptavidin affinity, and
      perhaps also for a major part of the catalytic function of hypoxanthine-guanine
      phosphoribosyltransferase and purine nucleoside phosphorylase (PNP). As
      successive NAD(+) molecules bind to the glyceraldehyde phosphate dehydrogenase
      tetramer, they do so with positively cooperative binding (using the term as
      applied in crystallization and protein folding) that decreases at each step. This
      binding is negatively cooperative in the usage stemming from Monod and co
      workers.

PMID- 20810305
TI  - Selective proteolysis sets the tempo of the cell cycle.
AB  - Ubiquitin-mediated proteolysis is one of the key mechanisms underlying cell cycle
      control in all eukaryotes. This is achieved by the action of ubiquitin ligases
      (E3s), which remove both negative and positive regulators of the cell cycle.
      Though our current understanding of the plant cell cycle has improved a lot these
      recent years, the identity of the E3s regulating it and their mode of action is
      still in its infancy. Nevertheless, recent research in Arabidopsis revealed some
      novel findings in this area. Thus the anaphase promoting complex/cyclosome
      (APC/C) not only controls mitotic events, but is also important in post-mitotic
      cells for normal plant development and cell differentiation. Moreover conserved
      and novel E3s were identified that target cyclin-dependent kinase inhibitors at
      different plant developmental stages. Finally, environmental constrains and
      stress hormones negatively impact on the cell cycle by processes that also
      include E3s.

PMID- 20810306
TI  - Secondary deuterium isotope effects on the acidity of glycine.
AB  - Secondary deuterium isotope effects (IE) on the acidity (pK(a)) of glycine were
      measured by 13C NMR titration. It was found that deuteration decreases the pK(a)
      by 0.034 +/- 0.002. The experimental data are supported by theoretical
      calculations, which, in turn, allowed to relate the acidity decrease to the
      lowering of glycine vibrational frequencies upon deuteration.

PMID- 20810307
TI  - Market segmentation of health information use on the Internet in Korea.
AB  - BACKGROUND: Internet is the common way to access all kind of information, thus it
      becomes to have highly influential place on the range of health care as well.
      More and more people have been using Internet to get the latest information on
      the health-related matters. However, it is very important but not easy to find
      the correct data and select it efficiently among the enormous amount of
      information. To identify the information seekers and understand their needs or
      purposes, they would be very effective for the providers to give high-quality
      health information for the Internet users. OBJECTIVES: The purpose of this study
      is to reveal the patterns of utilization of health information on the Internet.
      The subjects of the survey were randomly selected among the local residents by
      their age and gender. It was conducted in Gangwon, the province and Incheon, the
      metropolitan city at the same time. To investigate the similar amount of
      population, 0.5% of Gangwon and 0.3% of Incheon dwellers were chosen. METHODS:
      10,325 people were responded to the telephone poll and the investigation had been
      conducted from July to October 2006. 8656 from 10,325 completed the survey and
      1665 (19.2%) of them had used Internet to get health information in last 1-year.
      The use of health information on the Internet was classified into four categories
      as follows: general health tips, disease specific information, shopping for
      health commodities, and selection of hospitals. The questionnaire included
      articles regarding socio-demographic characteristics such as age, gender, income,
      education, dwelling area, health status and behaviors such as cigarette smoking
      and alcohol consumption. RESULTS: Of all 1665 respondents, 726 (17.2%) men (total
      4210) and 939 (21.1%) women (total 4446) had used Internet for health information
      in last 1-year. The health information that people wanted from Internet was as
      follows: general health tips (64.2%), disease specific information (32.0%),
      shopping for health commodities (23.7%), and selection of hospitals (19.3%). The
      people of higher education and higher income level tended to use Internet more
      often for health information. Metropolitan city dwellers used health information
      on the Internet more than people from province did. Personal health status
      appeared to be the most important factor to search the information about general
      health tips from the Internet. Healthy people (68.3%) used the Internet more than
      people with diseases (44.4%) who used Internet most frequently for disease
      specific information (62.6%). Residence area was the most important factor of
      online shopping for health commodities. While 31.8% of city dwellers used the
      Internet, only 19.0% of metropolitan or county dwellers used it for the same
      purpose. Determinant factors for the utilization of the Internet for hospital
      selection were residence area, age, and health examination. CONCLUSIONS: We found
      that each section of health information has its own clients concerning their
      personal interests and status of health and life style. That is why customized
      market segmentation is strongly recommended for their loyal customers. Depends on
      the information seekers' health status, it should be decided which information
      would be more useful for them between general health tips and specific disease.
      On the other hand, the area where the information seekers live can be more
      influential on terms of shopping for health commodities. These results will be a
      great help to start to understand the closer atmosphere of the ideal health
      information market to provide more valuable services in more various use.

PMID- 20810308
TI  - Muscle changes in amyotrophic lateral sclerosis: a longitudinal ultrasonography
      study.
AB  - OBJECTIVE: We performed a longitudinal study to assess structural muscle changes
      in amyotrophic lateral sclerosis (ALS) using ultrasonography. METHODS: During a
      follow-up of 6 months, ultrasonography parameters (muscle thickness, echo
      intensity and fasciculations) were obtained from 6 muscle groups in 31 ALS
      patients, together with strength and scores on the revised ALS functional rating
      scale (ALSFRS-r). RESULTS: At baseline, we found an increased echo intensity and
      decreased thickness, and these parameters correlated with lower strength.
      Moreover, ultrasound abnormalities were also detected in muscles with preserved
      strength. Longitudinal changes in echo intensity, muscle thickness and
      fasciculations showed large variations between patients. Rates of change in
      ultrasound parameters did not correlate with changes in ALSFRS-r or strength.
      CONCLUSION: In patients with ALS ultrasound abnormalities can be found in muscles
      with preserved strength. The pattern of ultrasonographic muscle changes in ALS is
      highly variable and shows no evident correlation with functional measures.
      SIGNIFICANCE: Ultrasonography is not suitable to monitor disease progression in
      ALS.

PMID- 20810309
TI  - RLS in middle aged women and attention deficit/hyperactivity disorder in their
      offspring.
AB  - BACKGROUND: Previous studies have suggested that attention deficit/hyperactivity
      disorder (ADHD) and restless legs syndrome (RLS) could share some common genetic
      backgrounds, but the effect of these genetic components could be modest. To test
      this hypothesis, we conducted a large-scaled cross-sectional study to examine
      whether women with a child with ADHD had a higher risk of having RLS than women
      of unaffected children. METHODS: We included 65,554 women free of diabetes,
      arthritis, and pregnancy in the current analyses. Information on RLS was assessed
      using a set of standardized questions. Participants were considered to have RLS
      if they met four RLS diagnostic criteria recommended by the International RLS
      Study Group and had restless legs >=5 times/month. Information on ADHD in
      offspring was collected via questionnaire. RESULTS: We observed a significant
      association between presence of ADHD in the offspring and risk of having RLS; the
      multivariate-adjusted OR for RLS was 1.27 (95% CI: 1.15, 1.41; P<0.0001), after
      adjusting for age, body mass index, number of deliveries during life time and
      other covariates. CONCLUSION: We found that mothers of children with ADHD had an
      increased risk of having RLS. Further studies are warranted to explore biological
      mechanisms underling this association.

PMID- 20810310
TI  - Injurious REM sleep behaviour disorder in narcolepsy with cataplexy contributing
      to criminal proceedings and divorce.
AB  - We present a case of violent sleep-related behaviour in a patient with narcolepsy
      with cataplexy (NC) and REM sleep behaviour disorder (RBD), causing injuries to
      his wife that resulted in charge of assault, followed by a divorce case. This
      observation pinpoints that RBD in NC can arise early in a patient's life and that
      it can be violent, that pharmacological treatment for RBD has to be considered in
      this case, that lack (or delay) of RBD diagnoses may further exacerbate the
      psychosocial burden of NC, and that a general awareness of the nature of sleep
      related violence may avoid unfortunate legal and personal consequences for
      patients, their partners and families.

PMID- 20810311
TI  - Modafinil reverses hypoexcitability of the motor cortex in narcoleptic patients:
      a TMS study.
AB  - OBJECTIVE: Although many animal and human studies have been performed, the exact
      mechanisms of action whereby modafinil promotes wakefulness are still not
      completely understood. We aimed to investigate the functional effects of
      modafinil on motor cortex excitability in patients with narcolepsy by means of
      transcranial magnetic stimulation (TMS) techniques. METHODS: In a double-blind
      and placebo-controlled design, 24 drug-naive narcoleptic patients with cataplexy
      and 20 control subjects were administered modafinil or placebo over a period of 4
      weeks. TMS was performed twice during the awake state before and at the end of
      treatment; measures of cortical excitability included central motor conduction
      time, resting motor threshold, short latency intracortical inhibition (SICI) and
      intracortical facilitation to paired-TMS. TMS measures were correlated with the
      conventional neurophysiological method of Multiple Sleep Latency Test (MSLT) and
      the subjective Epworth Sleepiness Scale (ESS). RESULTS: As previously reported,
      motor threshold and SICI were significantly increased in patients with
      narcolepsy; modafinil reversed this cortical hypoexcitability, but only SICI
      differences reached statistical significance. The Spearman rank correlation
      analysis revealed the highest correlation between SICI and the MSLT; a positive
      correlation was also found between SICI and the ESS, as well as between RMT and
      both measures of daytime sleepiness. CONCLUSIONS: This represents the first
      report investigating effects of modafinil on cortical excitability in human
      narcolepsy. Since SICI is thought to be directly related to GABA(A) intracortical
      inhibitory activity, we demonstrated that the dose of modafinil that induces a
      satisfactory wakefulness-promoting response in narcoleptic patients also causes
      decrease in GABAergic transmission.

PMID- 20810312
TI  - The effect of modafinil on cortical excitability in patients with narcolepsy: a
      randomized, placebo-controlled, crossover study.
AB  - OBJECTIVE: To investigate the effect of modafinil on cortical excitability in
      patients with narcolepsy using transcranial magnetic stimulation (TMS). METHODS:
      Nineteen drug-naive narcolepsy patients with cataplexy (10 males, 9 females, and
      mean age 28.5 years) and 25 age- and sex-matched healthy controls were recruited.
      In this double-blind, randomized, crossover study, patients and controls received
      a single dose of 400mg modafinil or placebo. Modafinil and placebo
      administrations were separated by a 2-week washout period. TMS parameters, such
      as resting motor thresholds (RMT), motor-evoked potential (MEP) amplitudes,
      cortical silent periods (CSP), short-interval intracortical inhibition (SICI),
      and intracortical facilitation (ICF), were measured before and 3h after
      administering modafinil or placebo. The differences of TMS parameters were
      statistically tested between patients and controls and between before and after
      modafinil or placebo administration. RESULTS: Narcolepsy patients had
      significantly increased CSP durations compared to controls (independent t-test,
      P<0.05), indicating decreased excitability of cortical networks in human
      narcolepsy. In patients after modafinil administration, MEP amplitudes, SICI, and
      ICF increased, and CSP duration shortened significantly, meaning enhanced motor
      excitability, whereas in controls modafinil did not change TMS parameters
      significantly. Placebo administration did not affect TMS parameters both in
      patients or controls. CONCLUSIONS: Narcolepsy patients with cataplexy showed
      decreased cortical excitability than normal healthy controls. Single dose
      modafinil significantly increased motor excitability in narcolepsy patients but
      had no effect in healthy controls.

PMID- 20810313
TI  - Energy expended by boys playing active video games.
AB  - The purpose of this study was to: (1) determine energy expenditure (EE) during a
      range of active video games (AVGs) and (2) determine whether EE during AVGs is
      influenced by gaming experience or fitness. Twenty-six boys (11.4+/-0.8 years)
      participated and performed a range of sedentary activities (resting, watching
      television and sedentary gaming), playing AVGs (Nintendo(r) Wii Bowling, Boxing,
      Tennis, and Wii Fit Skiing and Step), walking and running including a maximal
      fitness test. During all activities, oxygen uptake, heart rate and EE were
      determined. The AVGs resulted in a significantly higher EE compared to rest (63
      190%, p<=0.001) and sedentary screen-time activities (56-184%, p<=0.001). No
      significant differences in EE were found between the most active video games and
      walking. There was no evidence to suggest that gaming experience or aerobic
      fitness influenced EE when playing AVGs. In conclusion, boys expended more energy
      during active gaming compared to sedentary activities. Whilst EE during AVG is
      game-specific, AVGs are not intense enough to contribute towards the 60min of
      daily moderate-to-vigorous physical activity that is currently recommended for
      children.

PMID- 20810314
TI  - Simultaneous operation for multiple valvular disease and myasthenia in a woman.
AB  - Myasthenia gravis is a neuromuscular disorder, and the severe complication of
      myasthenic crisis is a life-threatening condition, usually induced by stress such
      as fever, trauma or a surgical procedure. Simultaneous heart surgery and
      thymectomy in a patient with concomitant heart disease and myasthenia gravis has
      been previously reported. We report a female patient with rheumatic valvular
      disease and myasthenia gravis who received triple heart valve surgery and
      thymectomy simultaneously. In her early recovery, two episodes of myasthenic
      crisis occurred which were treated promptly with a successful surgical outcome.

PMID- 20810316
TI  - Evaluating the biological complexity of animal models of human disease and
      emerging therapeutic modalities.

PMID- 20810315
TI  - Wnt and mammary stem cells: hormones cannot fly wingless.
AB  - The mammary stem cell and its local microenvironment are central for the
      maintenance of proper tissue homeostasis during normal development. Defining the
      hierarchical organization of the epithelial subtypes in the mammary gland and the
      molecular pathways guiding their development has begun to provide a framework for
      understanding how cancer stem cells sustain the progression and heterogeneity of
      breast cancers. The Wnt pathway plays a fundamental role in multiple adult stem
      cells, as well as in orchestrating proper mammary gland development and
      maintenance. These processes are intricately guided by the influence of systemic
      hormones and local factors. Alterations in Wnt signaling can skew the homeostatic
      balance of the mammary epithelium to drive malignant progression; however,
      complexities of Wnt pathway components present a challenge in understanding their
      physiological function.

PMID- 20810317
TI  - Mechanisms of adiponectin regulation and use as a pharmacological target.
AB  - Adiponectin is an insulin-sensitizing and anti-inflammatory fat cell hormone that
      has immense potential as a therapeutic target for a multitude of obesity
      associated diseases, including type 2 diabetes, NASH and atherosclerosis
      (Chandran M, Phillips SA, Ciaraldi T, Henry RR: Adiponectin: more than just
      another fat cell hormone?Diabetes Care 2003, 26:2442-2450). The adiponectin gene
      is located in chromosome 3q27, a susceptibility locus for T2DM and metabolic
      disorders (Saito K, Tobe T, Minoshima S, Asakawa S, Sumiya J, Yoda M, Nakano Y,
      Shimizu N, Tomita M: Organization of the gene for gelatin-binding protein
      (GBP28). Gene 1999, 229:67-73). Increased circulating levels of adiponectin are
      associated with improvement in the metabolic syndrome and reductions are strongly
      predictive of diabetes risk (Li S, Shin HJ, Ding EL, van Dam RM: Adiponectin
      levels and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA
      2009, 302:179-188. Extensive efforts have been made to understand how adiponectin
      levels can be elevated. The complex post-translational processing and secretion
      of adiponectin provides a rich area where pharmacologic manipulation may be
      developed to increase adiponectin levels in humans. Circulating adiponectin
      levels are increased by many commonly used drugs, such as statins, angiotensin
      converting enzyme (ACE) inhibitors, and thiazolidinediones (TZDs) providing an
      important opportunity to gain insight into the mechanisms underlying their
      effects. This review describes the cellular processes by which adiponectin is
      synthesized and secreted, current therapeutics known to affect this pathway and
      the potential for therapeutic manipulation in human subjects.

PMID- 20810318
TI  - The elusive identity of T follicular helper cells.
AB  - Follicular helper T (Tfh) cells provide help to B cells and allow formation of
      long-lived antibody responses. Despite an improved understanding of the molecular
      program that drives Tfh cell formation, their definition remains elusive: neither
      follicular homing ability, Bcl-6 expression nor IL-21 secretion are exclusive
      properties of T cells that help B cells, and not all follicular T cells are B
      cell helpers. Indeed some follicular T cells appear to be suppressive.
      Furthermore, Tfh cells evolve during an immune response and B cells that have
      recently bound antigen, germinal center (GC) B cells and plasmablasts interact
      with phenotypically distinct Tfh cells. Here we propose that distinction between
      non-GC Tfh and GC Tfh cells might reconcile emerging controversies on Tfh
      cytokine secretion and the requirement of T-B cell interactions and SAP
      expression for Tfh formation.

PMID- 20810320
TI  - Minimal ovarian stimulation (mini-IVF) for IVF utilizing vitrification and
      cryopreserved embryo transfer.
AB  - Gentle ovarian stimulation protocols, such as 'mini-IVF', have several potential
      advantages over conventional IVF protocols, including less medication and fewer
      injections, producing fewer eggs, but eggs of higher quality. The particular
      'mild' stimulation protocol called 'mini-IVF' is described. This protocol
      requires a reliable and cheap method for embryo cryopreservation such as
      vitrification, because of the negative impact of clomiphene citrate on the
      endometrium and since cryopreserved embryo transfers with this protocol have
      yielded much higher pregnancy rates than fresh transfers. In this series,
      patients were not denied treatment based on their day-3 FSH value or ovarian
      reserve. Yet very acceptable pregnancy rates were achieved (20% for fresh embryo
      transfers and 41% for cryopreserved embryo transfers). These results strengthen
      the argument for a mini-IVF protocol and vitrification as an alternative to
      standard conventional IVF stimulation protocols. Now a randomized control trial
      with cryopreserved single-embryo transfer is required.

PMID- 20810319
TI  - The emerging roles of melanopsin in behavioral adaptation to light.
AB  - The adaptation of behavior and physiology to changes in the ambient light level
      is of crucial importance to life. These adaptations include the light modulation
      of neuroendocrine function and temporal alignment of physiology and behavior to
      the day:night cycle by the circadian clock. These non-image-forming (NIF)
      responses can function independent of rod and cone photoreceptors but depend on
      ocular light reception, suggesting the participation of novel photoreceptors in
      the eye. The discovery of melanopsin in intrinsically photosensitive retinal
      ganglion cells (ipRGCs) and genetic proof for its important role in major NIF
      responses have offered an exciting entry point to comprehend how mammals adapt to
      the light environment. Here, we review the recent advances in our understanding
      of the emerging roles of melanopsin and ipRGCs. These findings now offer new
      avenues to understand the role of ambient light in sleep, alertness, dependent
      physiologies and potential pharmacological intervention as well as lifestyle
      modifications to improve the quality of life.

PMID- 20810321
TI  - Variable number of tandem repeat sequences act as regulatory elements in
      Mycobacterium tuberculosis.
AB  - VNTR (variable number of tandem repeats) has been used extensively for
      Mycobacterium tuberculosis strain discrimination. In contrast, their biological
      roles have been rarely investigated. We, herewith, studied whether two VNTR could
      promote expression of a downstream reporter gene, gfp. The VNTR loci, VNTR0960c
      and VNTR4052, reside upstream of the translational start sites of Rv0861c
      (helicase gene, ercc3) and Rv3610c (ftsH), respectively. Both are highly
      polymorphic among clinical strains of M. tuberculosis. DNA fragments containing
      various numbers of the repeat units were amplified and inserted upstream of the
      gfp gene and transformed into M. smegmatis mc(2)155 and M. tuberculosis H37Ra.
      The levels of fluorescence were determined by microplate fluorometry and flow
      cytometry. It was found that VNTR0960c could promote the expression of gfp while
      VNTR4052 alone could not. However, VNTR4052 was needed for complementing the
      promoter activity of the downstream sequence. The effects were discernible in M.
      tuberculosis, even though only the incomplete copy of the repeat was present. The
      addition of a complete copy of the repeat augmented the promoter activity. The
      presence of more copies of the repeat had minimal effects or even decreased the
      expressions. Significance of the effects on the cellular metabolisms of M.
      tuberculosis warrants further studies.

PMID- 20810322
TI  - The chemotherapy of tuberculous meningitis in children and adults.
AB  - Literature dealing with antituberculosis chemotherapy of tuberculous meningitis
      (TBM) in adults and children is reviewed and recommendations made for the
      chemotherapy of TBM. Publications relating to the chemotherapy of TBM were
      reviewed which contribute to understanding the efficacy of different drugs and
      regimens in TBM treatment. The established classification of disease severity
      into stages I (no neurological signs and fully conscious), II (patients conscious
      but with neurological signs) and III (comatose or stuporous or with severe
      pareses) was used to compare regimens of isoniazid (INH), para-amino salicylic
      acid and streptomycin (INH regimens) used up to approximately 1970 with those
      using INH and rifampicin (RMP), supported by pyrazinamide and ethambutol or
      streptomycin (RMP regimens). Mortality in studies at all disease stages in adults
      or adults and children, with the children not distinguished, following INH
      regimens (12.4%, 25.2% and 55% at stages I, II and III respectively) did not
      differ significantly from that following introduction of RMP regimens (9.7%,
      22.2% and 56% at stages I, II and III respectively), In studies of children only,
      mortality fell significantly following the introduction of RMP to 0%, 5.9% and
      28.2% in children at stage I, II and III having been 10.2%, 22.3% and 49.4%
      respectively with INH regimens (P = 0.006). Following RMP regimens of 6 months
      duration, only 2 (1%) relapses occurred amongst 197 patients, after RMP regimens
      of 9-24 months only 1 (0.16%) relapse was recorded amongst 632 patients. Where
      INH resistance rates are <4% a directly observed INH, RMP, pyrazinamide and
      ethambutol for 2-months followed by INH and RMP for 4 months is recommended. If
      directly observed therapy cannot be practiced treatment duration should be
      extended to at least 9 months; if the risk of INH resistance or multidrug
      resistance is higher, the use of ethionamide and a fluoroquinolone and possibly
      cycloserine is recommended and pyrazinamide should be continued for full
      treatment duration. The penetration of RMP, ethambutol and streptomycin into
      cerebrospinal fluid is poor; higher dosages of RMP should be considered.

PMID- 20810323
TI  - Planning locally relevant Internet programs for secondary prevention of
      cardiovascular disease.
AB  - BACKGROUND: Although the Internet has been shown to be an effective tool for
      supporting behavioural change in other chronic diseases, less in known about the
      efficacy of, or need for, Internet-based interventions in the prevention of
      coronary heart disease (CHD). AIMS: We investigated computer literacy, consumer
      need and perceived usefulness of the Internet as a secondary prevention tool in
      people with CHD. METHODS: A two-step mixed-method process was used that included
      a survey and two focus groups. The 12-item survey explored participants' access
      and confidence using the Internet. For the focus groups, we used standard
      methodology. RESULTS: We recruited 66 (88% response rate) consecutive cardiac
      patients; age 36-73 years (mean 64+/-13), mostly male (85%), whose primary
      language was predominantly English (67%). Seventy percent had a home computer
      with Internet access but only 20% reported researching their heart-health online.
      There was polarity between those with and without Internet access. Further, we
      found less women than men could complete online forms (p=0.03) and that
      participants aged over 65 years were less likely to access the Internet (p<0.01)
      and had lower confidence (p<0.01) than younger counterparts. Focus groups
      revealed challenges of an online secondary prevention service, but participants
      valued relevant, practical advice and placed strong emphasis on simple web
      design. CONCLUSION: Using a mixed-methods process we collected locally sensitive
      information about Internet usage and recommendations for future online health
      management strategies. Some patients have more confidence using the Internet,
      therefore a range of multi-technological secondary prevention interventions
      should be considered based on individual need.

PMID- 20810324
TI  - Disease progression model for cognitive deterioration from Alzheimer's Disease
      Neuroimaging Initiative database.
AB  - BACKGROUND: A mathematical model was developed to describe the longitudinal
      response in Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) obtained
      from the Alzheimer's Disease Neuroimaging Initiative. METHODS: The model was fit
      to the longitudinal ADAS-cog scores from 817 patients. Risk factors (age,
      apolipoprotein E4 [APOE E4] genotype, gender, family history of AD, years of
      education) and baseline severity were tested as covariates. RESULTS: Rate of
      disease progression increased with baseline severity. Age, APOE E4 genotype, and
      gender were identified as potential covariates influencing disease progression.
      The rate of disease progression in patients with mild to moderate AD was
      estimated as approximately 5.5 points/yr. CONCLUSIONS: A disease progression
      model adequately described the natural decline of ADAS-cog observed in
      Alzheimer's Disease Neuroimaging Initiative. Baseline severity is an important
      covariate to predict a curvilinear rate of disease progression in normal elderly,
      mild cognitive impairment, and AD patients. Age, APOE E4 genotype, and gender
      also influence the rate of disease progression.

PMID- 20810325
TI  - Determination of the major constituents in fruit of Arctium lappa L. by matrix
      solid-phase dispersion extraction coupled with HPLC separation and fluorescence
      detection.
AB  - The arctiin and arctigenin in the fruit of Arctium lappa L. were extracted by
      matrix solid-phase dispersion (MSPD) and determined by high-performance liquid
      chromatography (HPLC) with fluorescence detection. The experimental conditions
      for the MSPD were optimized. Silica gel was selected as dispersion adsorbent and
      methanol as elution solvent. The calibration curve showed good relationship
      (r>0.9998) in the concentration range of 0.010-5.0MUgmL(-1) for arctiin and 0.025
      7.5MUgmL(-1) for arctigenin. The recoveries were between 74.4% and 100%. The
      proposed method consumed less sample, time and solvent compared with conventional
      methods, including ultrasonic and Soxhlet extraction.

PMID- 20810326
TI  - Hydroxyapatite as a concentrating probe for phosphoproteomic analyses.
AB  - A novel method for the selective enrichment of casein
      phosphoproteins/phosphopeptides (CPP) from complex mixtures is reported herein.
      This method employs ceramic hydroxyapatite (HA) as a solid-phase adsorbent to
      efficiently capture phosphoproteins and CPP from complex media. Casein was chosen
      as the model phosphoprotein to test the protocol. CPP immobilized on HA
      microgranules formed a complex that was included in the matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI) matrix before desorbing directly
      from the well plate. Casein fractions with different levels of phosphorylation
      were desorbed based upon the specific concentration of trifluoroacetic acid (TFA)
      included in the MALDI matrix. The HA-bound casein enzymolysis was performed in
      situ with trypsin to remove non-phosphorylated peptides and isolate the
      immobilized CPP. The latter were recovered by centrifugation, dried, and co
      crystallized with a 1% phosphoric acid (PA) solution in the matrix that was
      appropriate for detecting CPP in MALDI-MS spectra. This approach for the
      selection of casein/CPP resulted in the identification of 32 CPP by MALDI-time of
      flight (TOF). The analytical process involved two steps requiring ~2h, excluding
      the time required for the enzymatic reaction. The alkaline phosphatase (AP)
      assisted de-phosphorylation of tryptic CPP allowed the phosphorylation level of
      peptides to be calculated concurrently with MALDI-TOF MS and liquid
      chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS). The
      effectiveness of the extraction procedure assayed on eggshell phosphoproteins
      resulted in the identification of 5 phosphoproteins and 14 derived
      phosphopeptides with a phosphoprotein global recovery of ~70% at least.

PMID- 20810327
TI  - Separation and purification of echinacoside from Penstemon barbatus (Can.) Roth
      by recycling high-speed counter-current chromatography.
AB  - Echinacoside is an important bioactive compound extracted from Cistanche tubulosa
      which was endangered by overexploitation. It is imperative to find an alternative
      source. Echinacoside was isolated from Penstemon barbatus (Can.) Roth for the
      first time. The peak contents of echinacoside are 9.09+/-0.32mg/g and 7.25+/
      0.36mg/g respectively in the leaves and roots annually. The methanolic extracts
      from 20g of dried powder of the roots of P. barbatus were pre-purified by AB-8
      resin and the fraction containing echinacoside was further purified by
      conventional high-speed counter-current chromatography (HSCCC) and recycling
      HSCCC with the solvent system n-butanol-water (1:1, v/v). Totally 42.0mg
      echinacoside with a purity of 96.3% was recovered. The recovery rate of
      echinacoside by recycling HSCCC reached 91.0%. The structure of our echinacoside
      confirmed by IR, (1)H NMR and (13)C NMR is identical to the standard sample. This
      indicates that P. barbatus might be ideal source for preparation of large scale
      of echinacoside.

PMID- 20810328
TI  - Process optimisation for anion exchange monolithic chromatography of 4.2kbp
      plasmid vaccine (pcDNA3F).
AB  - Anion exchange monolithic chromatography is increasingly becoming a prominent
      tool for plasmid DNA purification but no generic protocol is available to purify
      all types of plasmid DNA. In this work, we established a simple framework and
      used it to specifically purify a plasmid DNA model from a clarified alkaline
      lysed plasmid-containing cell lysate. The framework involved optimising ligand
      functionalisation temperature (30-80 degrees C), mobile phase flow rate (0.1
      1.8mL/min), monolith pore size (done by changing the porogen content in the
      polymerisation reaction by 50-80%), buffer pH (6-10), ionic strength of binding
      buffer (0.3-0.7M) and buffer gradient elution slope (1-10% buffer B/min). We
      concluded that preferential pcDNA3F adsorption and optimum resolution could be
      achieved within the tested conditions by loading the clarified cell lysate into
      400nm pore size of monolith in 0.7M NaCl (pH 6) of binding buffer followed by
      increasing the NaCl concentration to 1.0M at 3%B/min.

PMID- 20810329
TI  - Isolation of lignans from Schisandra chinensis with anti-proliferative activity
      in human colorectal carcinoma: Structure-activity relationships.
AB  - Separate benzocyclooctadiene lignans were isolated from the berries of Schisandra
      chinensis in milligram quantities on analytical reverse phase (RP) HPLC by an
      automated repeat-injection method and shown to have anti-proliferative activity
      against human colorectal cancer cells. Structures of the compounds were
      determined by a combination of NMR and mass spectrometry. Stereospecific NMR
      assignments for gomisin-N and deoxyschisandrin, gave more complete and accurate
      data than previously reported, based on 600MHz 2D HSQC, DQF-COSY and HMBC data.
      Comparison of coupling constants and HMBC crosspeak intensities with calculated
      and X-ray crystal structures confirmed their stereochemistry and conformation.
      Analysis of structure-activity relationships revealed the importance of key
      structural determinants. The S-biphenyl configuration of gomisin N, the most
      active lignan, correlated with increased anti-proliferative activity, while the
      presence of a hydroxyl group at the C7 position reduced or abolished this
      activity. Increased activity was also observed when a methylenedioxy group was
      present between C12 and C13. The percent yield of the most active compounds
      relative to the starting plant materials was 0.0156% for deoxyschisandrin and
      0.0173% for gomisin N. The results of these studies indicate that automated
      repeat-injection method of analytical HPLC may provide a superior alternative to
      the standard semi-preparative HPLC techniques for separation of complex mixtures.

PMID- 20810330
TI  - Determination of the unstable drug otilonium bromide in human plasma by LC-ESI-MS
      and its application to a pharmacokinetic study.
AB  - Otilonium bromide (OB) degrades rapidly in plasma and readily undergoes
      hydrolysis by the plasma esterase. In this paper, an LC-ESI-MS method has been
      developed for the determination of OB in human plasma. The rapid degradation of
      OB in plasma was well prevented by immediate addition of potassium fluoride (KF,
      an inhibitor of plasma esterase) to the freshly collected plasma before prompt
      treatment with acetonitrile. The method was validated over the concentration
      range of 0.1-20ng/ml. The data of intra-run and inter-run precision and accuracy
      were within +/-15%. The mean extraction recoveries for OB and the internal
      standard were higher than 93.0% and the matrix effects were negligible. The
      method has been successfully used in a pharmacokinetic study.

PMID- 20810331
TI  - Endoscopic ultrasonography-guided brushing increases cellular diagnosis of
      pancreatic cysts: A prospective study.
AB  - BACKGROUND: The diagnosis of pancreatic cystic lesions is still a challenge. AIM:
      To prospectively investigate the usefulness and safety of EUS-guided cytology
      brushing (EUS BR) in the cellular diagnosis of pancreatic cysts. METHODS: Cysts
      >15mm were sampled with a 19G needle. The fluid was aspirated and processed for
      cytology. The brush was introduced to scrub the cystic wall and processed as
      standard brushings. Antibiotic prophylaxis was administered. Complications were
      assessed in the first 24h and 7 days after the procedure. RESULTS: 30 patients
      were included. In 8 patients the technique failed for technical reasons. EUS BR
      provided with a cellular diagnosis in 20/22 cases (91%). The EUS BR was superior
      to the aspirated fluid for detecting diagnostic cells (73% vs. 36%, p=0.08) and
      mucinous cells (50% vs. 18%, p=0.016). In the 8 patients operated on, the
      specimen was consistent with EUS BR diagnosis. Three patients (10%) had
      complications, one of them a subacute retroperitoneal haemorrhage in a patient on
      anticoagulation therapy who died for complications 1 month later. CONCLUSIONS:
      EUS BR increases cellular diagnosis of pancreatic cystic lesions as compared with
      fluid analysis, mainly in mucinous lesions. Its use is not recommended in
      patients under anticoagulation therapy.

PMID- 20810335
TI  - An evaluation of a post-acute rehabilitation unit after five years of operations.
AB  - INTRODUCTION: The Hospital Organization Guidelines (HOG) recently recommended
      that Reference Hospitals create Post-Acute Rehabilitation Units (PARU). The
      authors describe the quality process of a PARU in a University Hospital (UH);
      this quality process had previously been used in a private rehabilitation
      hospital. GOALS: The authors wanted to evaluate the organization of the care
      provided in their PARU and compare the evaluation results with the results
      expected at the unit's creation five years earlier. METHODS: The evaluation
      indicators were set when the unit was created. These indicators allowed the
      evaluation of the appropriateness of admissions, the efficiency of the care path
      and the response to the patients' rehabilitation and intensive care needs.
      RESULTS: The appropriateness of admission was found to be coherent with the
      typology of patients admitted (i.e., brain and spinal cord injured patients just
      discharged from intensive care units). The brain-injured care path was
      streamlined. The evaluation results raised several questions about the resources
      provided and about the different needs of post-acute care and rehabilitation.
      DISCUSSION AND CONCLUSION: Patient needs must be identified precisely if the weak
      links of the care path are to be reinforced. The indicators used must be capable
      of assessing both the quantity and the quality of care. If these indicators lack
      relevance, or if the health care organization responds incompletely to patient
      needs, it puts the efficiency of the whole system at stake.

PMID- 20810336
TI  - Evaluation of cardiorespiratory functional reserve from arm exercise in the
      elderly.
AB  - BACKGROUND: When the subject is not able to satisfy traditional testing
      procedures, alternative exercises or indices such as arm cranking or the oxygen
      uptake efficiency slope (OUES) have been proposed. However, the OUES has not yet
      been used on elderly subjects from an exercise performed with the arms.
      OBJECTIVE: The aim of our study was to evaluate the possibility of using the OUES
      as an index of the cardiorespiratory functional reserve in the elderly when the
      exercise evaluation test is performed with the arms and when this parameter is
      estimated from submaximal responses. METHODS: Seventeen adults (62-82 years)
      undergoing total joint arthroplasty of the hip took part in this study. Maximal
      incremental exercise tests were performed on an arm crank ergometer 1 month
      before (T1) and 2 months after (T2) surgery. Gas exchanges were measured
      continuously to determine oxygen consumption at peak exercise (VO2 peak) and were
      used to calculate the OUES. The correlation coefficient was calculated between
      VO2 peak and OUES, and their relative changes between T1 and T2. RESULTS: VO2
      peak was not significantly different between T1 and T2: 10.3 +/- 0.7 and 9.8 +/-
      0.5 mL/min per kilogramme respectively. The OUES estimated from submaximal
      responses did not show a significant difference between T1 and T2. Significant
      correlations were observed between individual VO2 peak and OUES, as well as at T1
      and T2. CONCLUSION: The use of arm cranking exercises and the calculation of the
      OUES from the submaximal respiratory response can be used for the objective
      quantification of cardiorespiratory functional reserve in the elderly.

PMID- 20810339
TI  - An international prospective cohort study of mobile phone users and health
      (Cosmos): design considerations and enrolment.
AB  - BACKGROUND: There is continuing public and scientific interest in the possibility
      that exposure to radiofrequency (RF) electromagnetic fields (EMF) from mobile
      telephones or other wireless devices and applications might increase the risk of
      certain cancers or other diseases. The interest is amplified by the rapid world
      wide penetration of such technologies. The evidence from epidemiological studies
      published to date have not been consistent and, in particular, further studies
      are required to identify whether longer term (well beyond 10 years) RF exposure
      might pose some health risk. METHODS: The "Cosmos" study described here is a
      large prospective cohort study of mobile telephone users (ongoing recruitment of
      250,000 men and women aged 18+ years in five European countries - Denmark,
      Finland, Sweden, The Netherlands, UK) who will be followed up for 25+ years.
      Information on mobile telephone use is collected prospectively through
      questionnaires and objective traffic data from network operators. Associations
      with disease risks will be studied by linking cohort members to existing disease
      registries, while changes in symptoms such as headache and sleep quality and of
      general well-being are assessed by baseline and follow-up questionnaires.
      CONCLUSIONS: A prospective cohort study conducted with appropriate diligence and
      a sufficient sample size, overcomes many of the shortcomings of previous studies.
      Its major advantages are exposure assessment prior to the diagnosis of disease,
      the prospective collection of objective exposure information, long-term follow-up
      of multiple health outcomes, and the flexibility to investigate future changes in
      technologies or new research questions.

PMID- 20810340
TI  - Genetically engineered Salmon on the FDA's table.

PMID- 20810341
TI  - The changing landscape of arctic traditional food.

PMID- 20810343
TI  - Importance of particle size-fraction analysis in suspensions.

PMID- 20810345
TI  - Rice is a significant source of methylmercury: research in china assesses
      exposures.

PMID- 20810346
TI  - Residential history and groundwater modeling.

PMID- 20810347
TI  - Cold hard cache: the arctic drilling controversy.

PMID- 20810348
TI  - Pharmaceutical factories as a source of drugs in water.

PMID- 20810349
TI  - Picture of better health: prioritizing air pollution control in china.

PMID- 20810351
TI  - BPA and insulin resistance: evidence of effects in dams and offspring.

PMID- 20810352
TI  - Traffic trouble: study links diabetes to vehicular pollution.

PMID- 20810354
TI  - Health scenarios for a warming world.

PMID- 20810355
TI  - Cadmium alters the biotransformation of carcinogenic aromatic amines by arylamine
      N-acetyltransferase xenobiotic-metabolizing enzymes: molecular, cellular, and in
      vivo studies.
AB  - BACKGROUND: Cadmium (Cd) is a carcinogenic heavy metal of environmental concern.
      Exposure to both Cd and carcinogenic organic compounds, such as polycyclic
      aromatic hydrocarbons or aromatic amines (AAs), is a common environmental
      problem. Human arylamine N-acetyltransferases (NATs) are xenobiotic-metabolizing
      enzymes that play a key role in the biotransformation of AA carcinogens. Changes
      in NAT activity have long been associated with variations in susceptibility to
      different cancers in relation with exposure to certain AAs. OBJECTIVE: We
      explored the possible interactions between Cd and the NAT-dependent
      biotransformation of carcinogenic AAs. METHODS: We exposed purified enzymes, lung
      epithelial cells, and mouse models to Cd and subsequently analyzed NAT-dependent
      metabolism of AAs. RESULTS: We found that Cd, at biologically relevant
      concentrations, impairs the NAT-dependent acetylation of carcinogenic AAs such as
      2-aminofluorene (2-AF) in lung epithelial cells. NAT activity was strongly
      impaired in the tissues of mice exposed to Cd. Accordingly, mice exposed to Cd
      and 2-AF displayed altered in vivo toxicokinetics with a significant decrease (~
      50%) in acetylated 2-AF in plasma. We found that human NAT1 was rapidly and
      irreversibly inhibited by Cd [median inhibitory concentration (IC50) ~ 55 nM;
      rate inhibition constant (k(inact)) = 5 * 104 M-1 * sec-1], with results of
      acetyl coenzyme A (acetyl-CoA) protection assays indicating that Cd-mediated
      inhibition was due to the reaction of metal with the active-site cysteine residue
      of the enzyme. We found similar results for human NAT2, although this isoform was
      less sensitive to inactivation (IC50 ~ 1 MUM; k(inact) = 1 * 104 M-1 * sec-1).
      CONCLUSIONS: Our data suggest that Cd can alter the metabolism of carcinogenic
      AAs through the impairment of the NAT-dependent pathway, which may have important
      toxicological consequences.

PMID- 20810356
TI  - Dietary magnesium supplementation suppresses bone resorption via inhibition of
      parathyroid hormone secretion in rats fed a high-phosphorus diet.
AB  - This study examined the effects of dietary magnesium (Mg) supplementation on bone
      turnover and serum parathyroid hormone (PTH) levels in rats fed a high-phosphorus
      (P) diet. Male rats were randomized by weight into three groups, and fed a
      control diet (control), a high-P diet (HP) or a high-P and high-Mg diet (HPHMg)
      for 14 days. Serum osteocalcin levels were significantly higher in the HP and
      HPHMg groups than in the control group. Serum CTx levels were significantly
      higher in the HP and HPHMg groups than in the control group, while the levels in
      the HPHMg group were significantly lower than in the HP group. Serum PTH levels
      were significantly higher in the HP group than in the control and HPHMg groups.
      Dietary Mg supplementation had a significant influence on serum PTH levels in the
      HP and HPHMg groups. These results suggest that dietary Mg supplementation
      suppresses the high bone resorption induced by a high-P diet via inhibition of
      PTH secretion. Moreover, our results suggest that dietary Mg supplementation may
      be beneficial for the prevention of bone loss with high-P diet administration.

PMID- 20810357
TI  - A little humour relaxes the gallbladder.

PMID- 20810358
TI  - Silencing vascular smooth muscle ATP-sensitive K+ channels with caveolin-1.

PMID- 20810359
TI  - Should patients with haemorrhage be kept warm?

PMID- 20810360
TI  - Quantifying needles in a haystack: the firing properties of single sympathetic
      vasoconstrictor neurones in chronic obstructive pulmonary disease.

PMID- 20810361
TI  - An introduction to Peter Stanfield's festschrift.

PMID- 20810362
TI  - The cover. Tibetan altar with domestic motifs.

PMID- 20810363
TI  - A piece of my mind. Holding the hand.

PMID- 20810364
TI  - High heart rate may raise health risks.

PMID- 20810365
TI  - New rules call for more oversight, fewer hours for first-year residents.

PMID- 20810366
TI  - Obstetrics group relaxes guideline for trial of labor after cesarean delivery.

PMID- 20810367
TI  - Screening misses high LDL in many youths.

PMID- 20810368
TI  - Estrogen spray poses risks to children, pets through contact with treated skin.

PMID- 20810369
TI  - Prenatal and postpartum depression in fathers and mothers.

PMID- 20810370
TI  - Family income supplements and development of psychiatric and substance use
      disorders among an American Indian population.

PMID- 20810371
TI  - Severe pneumonia among Kenyan infants and children.

PMID- 20810372
TI  - Severe pneumonia among Kenyan infants and children.

PMID- 20810373
TI  - Randomized controlled trials with statistically nonsignificant results.

PMID- 20810374
TI  - Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with
      cancer risk and mortality.
AB  - CONTEXT: Mastectomy and salpingo-oophorectomy are widely used by carriers of
      BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer.
      OBJECTIVE: To estimate risk and mortality reduction stratified by mutation and
      prior cancer status. DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter
      cohort study of 2482 women with BRCA1 or BRCA2 mutations ascertained between 1974
      and 2008. The study was conducted at 22 clinical and research genetics centers in
      Europe and North America to assess the relationship of risk-reducing mastectomy
      or salpingo-oophorectomy with cancer outcomes. The women were followed up until
      the end of 2009. MAIN OUTCOMES MEASURES: Breast and ovarian cancer risk, cancer
      specific mortality, and overall mortality. RESULTS: No breast cancers were
      diagnosed in the 247 women with risk-reducing mastectomy compared with 98 women
      of 1372 diagnosed with breast cancer who did not have risk-reducing mastectomy.
      Compared with women who did not undergo risk-reducing salpingo-oophorectomy,
      women who underwent salpingo-oophorectomy had a lower risk of ovarian cancer,
      including those with prior breast cancer (6% vs 1%, respectively; hazard ratio
      [HR], 0.14; 95% confidence interval [CI], 0.04-0.59) and those without prior
      breast cancer (6% vs 2%; HR, 0.28 [95% CI, 0.12-0.69]), and a lower risk of first
      diagnosis of breast cancer in BRCA1 mutation carriers (20% vs 14%; HR, 0.63 [95%
      CI, 0.41-0.96]) and BRCA2 mutation carriers (23% vs 7%; HR, 0.36 [95% CI, 0.16
      0.82]). Compared with women who did not undergo risk-reducing salpingo
      oophorectomy, undergoing salpingo-oophorectomy was associated with lower all
      cause mortality (10% vs 3%; HR, 0.40 [95% CI, 0.26-0.61]), breast cancer-specific
      mortality (6% vs 2%; HR, 0.44 [95% CI, 0.26-0.76]), and ovarian cancer-specific
      mortality (3% vs 0.4%; HR, 0.21 [95% CI, 0.06-0.80]). CONCLUSIONS: Among a cohort
      of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was
      associated with a lower risk of breast cancer; risk-reducing salpingo
      oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis
      of breast cancer, all-cause mortality, breast cancer-specific mortality, and
      ovarian cancer-specific mortality.

PMID- 20810375
TI  - Cerebral palsy among term and postterm births.
AB  - CONTEXT: Although preterm delivery is a well-established risk factor for cerebral
      palsy (CP), preterm deliveries contribute only a minority of affected infants.
      There is little information on the relation of CP risk to gestational age in the
      term range, where most CP occurs. OBJECTIVE: To determine whether timing of birth
      in the term and postterm period is associated with risk of CP. DESIGN, SETTING,
      AND PARTICIPANTS: Population-based follow-up study using the Medical Birth
      Registry of Norway to identify 1,682,441 singleton children born in the years
      1967-2001 with a gestational age of 37 through 44 weeks and no congenital
      anomalies. The cohort was followed up through 2005 by linkage to other national
      registries. MAIN OUTCOME MEASURES: Absolute and relative risk of CP for children
      surviving to at least 4 years of age. RESULTS: Of the cohort of term and postterm
      children, 1938 were registered with CP in the National Insurance Scheme. Infants
      born at 40 weeks had the lowest risk of CP, with a prevalence of 0.99/1000 (95%
      confidence interval [CI], 0.90-1.08). Risk for CP was higher with earlier or
      later delivery, with a prevalence at 37 weeks of 1.91/1000 (95% CI, 1.58-2.25)
      and a relative risk (RR) of 1.9 (95% CI, 1.6-2.4), a prevalence at 38 weeks of
      1.25/1000 (95% CI, 1.07-1.42) and an RR of 1.3 (95% CI, 1.1-1.6), a prevalence at
      42 weeks of 1.36/1000 (95% CI, 1.19-1.53) and an RR of 1.4 (95% CI, 1.2-1.6), and
      a prevalence after 42 weeks of 1.44 (95% CI, 1.15-1.72) and an RR of 1.4 (95% CI,
      1.1-1.8). These associations were even stronger in a subset with gestational age
      based on ultrasound measurements: at 37 weeks the prevalence was 1.17/1000 (95%
      CI, 0.30-2.04) and the relative risk was 3.7 (95% CI, 1.5-9.1). At 42 weeks the
      prevalence was 0.85/1000 (95% CI, 0.33-1.38) and the relative risk was 2.4 (95%
      CI, 1.1-5.3). Adjustment for infant sex, maternal age, and various socioeconomic
      measures had little effect. CONCLUSION: Compared with delivery at 40 weeks'
      gestation, delivery at 37 or 38 weeks or at 42 weeks or later was associated with
      an increased risk of CP.

PMID- 20810377
TI  - Perinatal regionalization for very low-birth-weight and very preterm infants: a
      meta-analysis.
AB  - CONTEXT: For more than 30 years, guidelines for perinatal regionalization have
      recommended that very low-birth-weight (VLBW) infants be born at highly
      specialized hospitals, most commonly designated as level III hospitals. Despite
      these recommendations, some regions continue to have large percentages of VLBW
      infants born in lower-level hospitals. OBJECTIVE: To evaluate published data on
      associations between hospital level at birth and neonatal or predischarge
      mortality for VLBW and very preterm (VPT) infants. DATA SOURCES: Systematic
      search of published literature (1976-May 2010) in MEDLINE, CINAHL, EMBASE, and
      PubMed databases and manual searches of reference lists. STUDY SELECTION AND DATA
      EXTRACTION: Forty-one publications met a priori inclusion criteria (randomized
      controlled trial, cohort, and case-control studies measuring neonatal or
      predischarge mortality among live-born infants < or = 1500 g or < or = 32 weeks'
      gestation delivered at a level III vs lower-level facility). Paired reviewers
      independently assessed publications for inclusion and extracted data using
      standardized forms. Discrepancies were decided by a third reviewer. Publications
      were reviewed for quality by 3 authors based on 2 content areas: adjustment for
      confounding and description of hospital levels. We calculated weighted, combined
      odds ratios (ORs) using a random-effects model and comparative unadjusted pooled
      mortality rates. DATA SYNTHESIS: We observed increased odds of death for VLBW
      infants (38% vs 23%; adjusted OR, 1.62; 95% confidence interval [CI], 1.44-1.83)
      and VPT infants (15% vs 17%; adjusted OR, 1.55; 95% CI, 1.21-1.98) born outside
      of level III hospitals. Consistent results were obtained when restricted to
      higher-quality evidence (mortality in VLBW infants, 36% vs 21%; adjusted OR,
      1.60; 95% CI, 1.33-1.92 and in VPT infants, 7% vs 12%; adjusted OR, 1.42; 95% CI,
      1.06-1.88) and infants weighing less than 1000 g (59% vs 32%; adjusted OR, 1.80;
      95% CI, 1.31-2.46). No significant differences were found through subgroup
      analysis of study characteristics. Meta-regression by year of publication did not
      reveal a change over time (slope, 0.00; P = .87). CONCLUSION: For VLBW and VPT
      infants, birth outside of a level III hospital is significantly associated with
      increased likelihood of neonatal or predischarge death.

PMID- 20810376
TI  - A biobehavioral home-based intervention and the well-being of patients with
      dementia and their caregivers: the COPE randomized trial.
AB  - CONTEXT: Optimal treatment to postpone functional decline in patients with
      dementia is not established. OBJECTIVE: To test a nonpharmacologic intervention
      realigning environmental demands with patient capabilities. DESIGN, SETTING, AND
      PARTICIPANTS: Prospective 2-group randomized trial (Care of Persons with Dementia
      in their Environments [COPE]) involving patients with dementia and family
      caregivers (community-living dyads) recruited from March 2006 through June 2008
      in Pennsylvania. INTERVENTIONS: Up to 12 home or telephone contacts over 4 months
      by health professionals who assessed patient capabilities and deficits; obtained
      blood and urine samples; and trained families in home safety, simplifying tasks,
      and stress reduction. Control group caregivers received 3 telephone calls and
      educational materials. MAIN OUTCOME MEASURES: Functional dependence, quality of
      life, frequency of agitated behaviors, and engagement for patients and well
      being, confidence using activities, and perceived benefits for caregivers at 4
      months. RESULTS: Of 284 dyads screened, 270 (95%) were eligible and 237 (88%)
      randomized. Data were collected from 209 dyads (88%) at 4 months and 173 (73%) at
      9 months. At 4 months, compared with controls, COPE patients had less functional
      dependence (adjusted mean difference, 0.24; 95% CI, 0.03-0.44; P = .02; Cohen d =
      0.21) and less dependence in instrumental activities of daily living (adjusted
      mean difference, 0.32; 95% CI, 0.09-0.55; P = .007; Cohen d = 0.43), measured by
      a 15-item scale modeled after the Functional Independence Measure; COPE patients
      also had improved engagement (adjusted mean difference, 0.12; 95% CI, 0.07-0.22;
      P = .03; Cohen d = 0.26), measured by a 5-item scale. COPE caregivers improved in
      their well-being (adjusted mean difference in Perceived Change Index, 0.22; 95%
      CI, 0.08-0.36; P = .002; Cohen d = 0.30) and confidence using activities
      (adjusted mean difference, 0.81; 95% CI, 0.30-1.32; P = .002; Cohen d = 0.54),
      measured by a 5-item scale. By 4 months, 64 COPE dyads (62.7%) vs 48 control
      group dyads (44.9%) eliminated 1 or more caregiver-identified problems (chi(2/1)
      = 6.72, P = . 01). CONCLUSION: Among community-living dyads, a nonpharmacologic
      biobehavioral environmental intervention compared with control resulted in better
      outcomes for COPE dyads at 4 months. Although no group differences were observed
      at 9 months for patients, COPE caregivers perceived greater benefits. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00259454.

PMID- 20810378
TI  - A new research and development policy framework for the biomedical research
      enterprise.

PMID- 20810379
TI  - A national strategy to improve sexual health.

PMID- 20810380
TI  - Improving access to health care data: the Open Government strategy.

PMID- 20810381
TI  - Societal perceptions of physicians: knights, knaves, or pawns?

PMID- 20810382
TI  - Lessons learned from genetic testing.

PMID- 20810383
TI  - JAMA patient page. Cerebral palsy.

PMID- 20810384
TI  - Synergistic antitumor activity of sorafenib in combination with epidermal growth
      factor receptor inhibitors in colorectal and lung cancer cells.
AB  - PURPOSE: Cancer cell survival, invasion, and metastasis depend on cancer cell
      proliferation and on tumor-induced angiogenesis. We evaluated the efficacy of the
      combination of sorafenib and erlotinib or cetuximab. EXPERIMENTAL DESIGN:
      Sorafenib, erlotinib, and cetuximab, alone or in combination, were tested in
      vitro in a panel of non-small cell lung cancer (NSCLC) and colorectal cancer cell
      lines and in vivo in H1299 tumor xenografts. RESULTS: Epidermal growth factor
      receptor (EGFR) ligand mRNAs were expressed in all NSCLC and colorectal cancer
      cell lines with variable levels ranging from 0.4- to 8.1-fold as compared with
      GEO colorectal cancer cells. Lung cancer cells had the highest levels of vascular
      endothelial growth factors (VEGF) A, B, and C, and of VEGF receptors as compared
      with colorectal cancer cells. Combined treatments of sorafenib with erlotinib or
      cetuximab produced combination index values between 0.02 and 0.5, suggesting a
      significant synergistic activity to inhibit soft agar colony formation in all
      cancer cell lines, which was accompanied by a marked blockade in mitogen
      activated protein kinase and AKT signals. The in vitro migration of H1299 cells,
      which expressed high levels of both VEGF ligands and receptors, was inhibited by
      treatment with sorafenib, and this effect was significantly increased by the
      combination with anti-EGFR drugs. In nude mice bearing established human H1299
      xenografts, treatment with the combination of sorafenib and erlotinib or
      cetuximab caused a significant tumor growth delay resulting in 70 to 90 days
      increase in mice median overall survival as compared with single-agent sorafenib
      treatment. CONCLUSIONS: Combination treatment with sorafenib and erlotinib or
      cetuximab has synergistic antitumor effects in human colorectal and lung cancer
      cells.

PMID- 20810388
TI  - School-based physical activity and fitness promotion.

PMID- 20810387
TI  - Neurotensin receptor 1 determines the outcome of non-small cell lung cancer.
AB  - PURPOSE: This study aimed to investigate the role of the neurotensin/neurotensin
      receptor I (NTSR1) complex in non-small cell lung cancer (NSCLC) progression.
      EXPERIMENTAL DESIGN: The expression of neurotensin and NTSR1 was studied by
      transcriptome analysis and immunohistochemistry in two series of 74 and 139
      consecutive patients with pathologic stage I NSCLC adenocarcinoma. The findings
      were correlated with clinic-pathologic features. Experimental tumors were
      generated from the malignant human lung carcinoma cell line A459, and a subclone
      of LNM35, LNM-R. The role of the neurotensin signaling system on tumor growth and
      metastasis was investigated by small hairpin RNA-mediated silencing of NTSR1 and
      neurotensin. RESULTS: Transcriptome analysis carried out in a series of 74
      patients showed that the positive regulation of NTSR1 put it within the top 50
      genes related with relapse-free survival. Immunohistochemistry revealed
      neurotensin- and NTSR1-positive staining in 60.4% and 59.7% of lung
      adenocarcinomas, respectively. At univariate analysis, NTSR1 expression was
      strongly associated with worse 5-year overall survival rate (P = 0.0081) and
      relapse-free survival (P = 0.0024). Multivariate analysis showed that patients
      over 65 years of age (P = 0.0018) and NTSR1 expression (P = 0.0034) were
      independent negative prognostic factors. Experimental tumor xenografts generated
      by neurotensin- and NTSR1-silenced human lung cancer cells revealed that
      neurotensin enhanced primary tumor growth and production of massive nodal
      metastasis via autocrine and paracrine regulation loops. CONCLUSION: NTSR1
      expression was identified as a potential new prognostic biomarker for surgically
      resected stage I lung adenocarcinomas, as NTSR1 activation was shown to
      participate in lung cancer progression.

PMID- 20810389
TI  - Invited commentary.

PMID- 20810390
TI  - Invited commentary.

PMID- 20810391
TI  - Invited commentary.

PMID- 20810392
TI  - Benzodiazepines provide no additional benefit over physiotherapy and analgesia in
      acute lumbar disc prolapse.

PMID- 20810393
TI  - Endogenous regeneration after collagenase-induced knee joint damage in the adult
      newt Notophthalmus viridescens.
AB  - OBJECTIVES: To determine whether adult newts (Notophthalmus viridescens) are able
      to repair experimentally-induced joint damage in order to generate a model system
      for the study of endogenous joint regeneration. METHODS: Joint instability and
      articular cartilage lesions of the knee joint of adult newts (N viridescens) were
      induced by intra-articular injection of collagenase. The changes over time were
      analysed clinically, by MRI, histologically and by reverse transcription PCR to
      detect selected relevant markers. RESULTS: After rapid onset of disease with
      joint luxation, loss of proteoglycans and cartilage volume, the signs ameliorated
      continuously by regeneration of the affected joint compartments. The majority of
      joints were morphologically intact and functionally operative after 10 weeks.
      Upregulation of chondrogenic key genes, homogenous expression levels of factors
      implicated in cartilage homeostasis and limb regeneration as well as the
      distribution of the blastemal marker 22/18 in both treated and untreated knees
      suggest that joint regeneration in adult newts only partially invokes pathways of
      embryological organogenesis. CONCLUSIONS: Newts are able to regenerate articular
      cartilage injuries and to restore tissue integrity and function after induction
      of damage using a procedure known to induce experimental osteoarthritis in murine
      models. Further analysis of the underlying molecular mechanisms may contribute to
      the development of novel treatment approaches in joint failure.

PMID- 20810394
TI  - Etanercept plus ciclosporin versus etanercept plus methotrexate for maintaining
      clinical control over psoriatic arthritis: a randomised pilot study.

PMID- 20810395
TI  - MRI in early rheumatoid arthritis: synovitis and bone marrow oedema are
      independent predictors of subsequent radiographic progression.
AB  - OBJECTIVES: To determine whether MRI and conventional (clinical and laboratory)
      measures of inflammation can predict 3-year radiographic changes measured by the
      van der Heijde Sharp score in patients with early rheumatoid arthritis (RA).
      METHODS: 55 patients with RA with disease duration <1 year participated in this 3
      year follow-up study. Patients were evaluated at baseline, 3, 6, 12 and 36 months
      by swollen and tender joint count, disease activity score based on 28-joint
      count, erythrocyte sedimentation rate (ESR), C reactive protein, MRI measures of
      synovitis, bone marrow oedema and tenosynovitis of the dominant wrist, as well as
      conventional x-rays of the hands and wrists. RESULTS: All measures of
      inflammation decreased during the follow-up period. ESR, MRI synovitis and MRI
      bone marrow oedema were independent predictors of 3-year radiographic progression
      adjusted for age, sex and anti-citrullinated protein antibodies. The 1-year
      cumulative measures of MRI synovitis and bone marrow oedema provided an improved
      explanation of variation (adjusted R(2)) in radiographic change compared with the
      baseline MRI values (adjusted R(2)=0.32 and 0.20 vs 0.11 and 0.04, respectively).
      CONCLUSIONS: Both baseline and 1-year cumulative measures of MRI synovitis and
      bone marrow oedema independently predicted 3-year radiographic progression. These
      results confirm that MRI synovitis and MRI bone marrow oedema precede
      radiographic progression in patients with early RA.

PMID- 20810396
TI  - Frenulectomy - the child has rights!

PMID- 20810397
TI  - Nocturnal hypoventilation: predictors and outcomes in childhood progressive
      neuromuscular disease.
AB  - OBJECTIVES: To determine: (a) prevalence of clinically unsuspected nocturnal
      hypoventilation (NH) in a clinic population of children with progressive
      neuromuscular disease; (b) whether NH can be predicted from clinical/laboratory
      parameters; and (c) change over 1 year in pulmonary function decline, quality of
      life and attention in children with NH treated with non-invasive positive
      pressure ventilation (NPPV) compared with children without NH. DESIGN:
      Prospective cohort study. SETTING: Two tertiary-care paediatric neuromuscular
      clinics. PATIENTS: 46 children (6-17 years) with progressive neuromuscular
      disease without neurocognitive impairment or dystrophinopathy. INTERVENTIONS:
      Polysomnography, pulmonary function, manual muscle strength, quality of life (CHQ
      PF50) and Conners questionnaires. OUTCOME MEASURES: (a) Prevalence of NH; (b)
      predictive value of surrogate clinical measures for NH; and (c) differences in
      change over 1 year in pulmonary function, muscle strength, quality of life and
      attention between children with and without NH. RESULTS: Prevalence of NH was
      14.8%, 95% CI 8.0% to 25.7%. Maximal sensitivity and specificity for NH were
      achieved with thresholds of forced vital capacity <70% and forced expiratory
      volume in 1 s <65% predicted (sensitivities: 71.4, 71.4; specificities: 64.1,
      79.5). Scoliosis also predicted NH (sensitivity 88.9; specificity 80.4). Over 1
      year, those with NH had a greater increase in residual volume/total lung capacity
      (0.075 (-0.003 to 0.168) vs -0.03 (-0.065 to 0.028)), decline in muscle strength
      (-0.67 (-0.90 to 0.10) vs 0.53 (-0.05 to 0.90)) and worsened perception of health
      status. CONCLUSIONS: 15% of subjects had clinically unsuspected NH, predicted by
      moderate pulmonary function test impairment and scoliosis. Over 1 year those with
      NH had increased gas trapping, decline of muscle strength and worse perception of
      health status, despite NPPV.

PMID- 20810398
TI  - Compliance with NICE guidelines for urinary tract infections: a survey among the
      paediatric trainees of the London Deanery.

PMID- 20810399
TI  - Mycophenolate mofetil treatment in children and adolescents with lupus.
AB  - Safety and efficacy data are presented on the use of mycophenolate mofetil (MMF)
      in 26 children and adolescents with lupus. Data include therapy before and 12
      months after starting MMF. 18 of 26 patients had biopsy-proved lupus nephritis.
      Group 1 were commenced on MMF induction and/or maintenance therapy (n=14), group
      2 converted from azathioprine because of inadequate disease control (n=12). 73%
      of all (10 (71%) group 1 and 10 (83%) group 2) patients experienced a significant
      improvement in British Isles Lupus Assessment Group score (from median 9.0 to
      3.0). Children with hypocomplementaemia increased their C3 significantly in both
      groups (0.53-1.15 for group 1 and 0.63-1.2 g/l for group 2, p=0.001), and C4
      level only in group 1 (0.08-0.17, p=0.01). Renal function and albuminuria
      improved in those with active nephritis (p<=0.01). Significant improvements were
      seen in both groups in haemoglobin, erythrocyte sedimentation rate and lymphocyte
      counts. Prednisolone dose was weaned in both groups, p<0.05. Side-effects were
      seen in four patients, but none was judged to be severe enough to discontinue
      treatment. MMF treatment in this cohort of children with lupus seemed to be safe,
      well tolerated and effective.

PMID- 20810400
TI  - Children's access to treatment for epilepsy: experience from the Lao People's
      Democratic Republic.
AB  - Epilepsy affects an estimated 10.5 million children worldwide, of whom 80% live
      in developing countries. The treatment gap is estimated at around 90% in the Lao
      People's Democratic Republic (Lao PDR). The present work analyses some of the
      reasons that could explain the low access to antiepileptic drugs (AED) for
      children with epilepsy in the Lao PDR. Epilepsy, the 'mad pig disease', is highly
      neglected. Traditional beliefs, fear and stigma are common among the general
      population and shared by 40% of health staff. Poor knowledge of the disease and
      its treatment, low trust in modern treatment, restricted access to AED and
      ignorance of long-term treatment explain the low access to AED. Improving
      understanding of epilepsy and its treatment, will improve the treatment gap for
      epileptic children in the Lao PDR.

PMID- 20810401
TI  - Images in paediatrics. Childhood melanoma.

PMID- 20810402
TI  - Femoral profunda artery aneurysm as an unusual first presentation of Behcet
      disease.
AB  - Behcet disease is a multisystem inflammatory disorder, rarely found in African
      Americans. Arterial involvement occurs in less than 8% of patients. Profunda
      femoral artery aneurysms (PFAAs) are extremely rare and often occur with
      synchronous aneurysms. We present a case of an African American man diagnosed
      with Behcet disease from his presentation with PFAA. He was also found to have a
      synchronous hypogastric artery aneurysm. The patient was immediately treated with
      corticosteroids and infliximab to control systemic and vascular inflammation,
      returning 1 month later for surgery. He had a repair of the left PFAA with a
      common femoral to profunda femoris artery bypass with reversed saphenous vein
      graft and aneurysmorrhaphy. When a patient presents with an aneurysm in an
      unusual location, it is important to evaluate for other aneurysms. A careful
      history and physical examination is also required to see if the aneurysm may be
      part of an underlying systemic syndrome.

PMID- 20810403
TI  - Is endovascular stent-graft treatment of primary aortoesophageal fistula
      worthwhile?
AB  - Aortoesophageal fistula (AEF) as a result of prolonged nasogastric intubation is
      rare and certainly fatal, without prompt surgical intervention. We report the
      case of a 41-year-old man with morbid obesity who was admitted after suffering
      55% of total body surface area burns. After several skin graft operations over
      the course of 12 weeks, he was rushed into surgery because of the acute onset of
      severe upper gastrointestinal bleeding. Exploratory laparotomy and
      esophagogastroduodenoscopy (EGD) suggested an AEF, which was then quickly
      confirmed by a diagnostic angiogram. An endovascular aortic stent graft repair
      was performed that successfully stopped the bleeding. We include a review of the
      literature pertaining to cases of AEF treated by endovascular surgery, which
      appears to be a promising alternative to open surgery in the unfit patient.

PMID- 20810404
TI  - Sinus pericranii: case report.
AB  - Sinus pericranii (SP) is an abnormal communication between the intracranial and
      extracranial venous drainage pathways. Treatment of this condition has mainly
      been recommended for aesthetic reasons and prevention of hemorrhage. The authors
      report a conservative treatment for the potentially lethal complications.

PMID- 20810405
TI  - Cost-effective diagnostic strategies in patients with a high, intermediate, or
      low clinical probability of pulmonary embolism.
AB  - Rapid quantitative D-dimer assays (DD), lower extremity venous duplex
      ultrasonography (US), and multislice computed tomographic (CT) angiography have
      been shown to have adequate sensitivities and specificities for diagnostic
      purpose. The purpose of this study was to evaluate cost-effectiveness of
      diagnostic strategies for pulmonary embolism (PE) in patients with a high,
      intermediate, or low clinical probability of PE. A formal cost-effectiveness
      analysis for the diagnosis of PE was performed. The main outcome measure for
      effectiveness was 3-month expected survival. The strategy of DD followed by CT
      was cost-effective and had the lowest cost per life saved for all patients
      suspected with PE. The conventional strategy including ventilation and perfusion
      lung scanning followed by pulmonary angiography (PA) or CT was not cost
      effective. The leg US after CT was not also cost-effective. In clinical practice,
      the individual patient's condition should be considered when choosing appropriate
      diagnostic tests.

PMID- 20810407
TI  - In vivo study on the expression pattern of resistin in patients with abdominal
      aortic aneurysm.
AB  - OBJECTIVE: To study the expression pattern of resistin in abdominal aortic
      aneurysms and to correlate its plasma levels to aneurysm size and statin therapy.
      PATIENTS AND METHODS: From 25 patients on regular and 38 patients without statin
      therapy tissue specimen and plasma samples were obtained for analysis. RESULTS:
      Demographic data, past medical history, and body mass index showed no significant
      differences between the statin and no statin group. Immunohistochemistry showed
      positive stainings for resistin in all sections and in part colocalization to CD
      68 positive cells. Patients with large aneurysms showed significant correlation
      of C-reactive protein (CRP) and interleukin 10 (IL-10) levels; patients on statin
      medication had significantly lower plasma levels of resistin and CRP. CONCLUSION:
      In contrast to IL-10 and CRP plasma levels of resistin are not correlated to
      aneurysm diameter; yet statin therapy results in decrease of resistin and CRP,
      suggesting an anti-inflammatory action in patients with abdominal aortic
      aneurysms (AAAs).

PMID- 20810406
TI  - Eversion endarterectomy for external iliac artery occlusive disease.
AB  - INTRODUCTION: The advent of effective endovascular techniques has revolutionized
      the treatment of iliac occlusive disease. Long-segment iliac occlusions remain
      technically difficult to treat, particularly in the presence of femoral disease.
      Iliac endarterectomy is an established procedure for the treatment of iliac
      occlusive disease, but it has been suggested that in the era of effective
      endovascular intervention, its role is limited. METHODS: A review of all patients
      who had eversion endarterectomy of the external iliac artery from a single
      institution between 2000 and 2008. RESULTS: Twenty-one patients (18 male)
      underwent eversion external iliac endarterectomy, 15 for external iliac and 6 for
      iliofemoral disease. Mean age was 64.7 years (range: 46-78 years) and the modal
      American Society of Anaesthesiologists (ASA) grade was 3. The indications were
      critical ischemia (n = 16) and disabling claudication (n = 5). Twelve had
      adjunctive procedures. The mean follow-up was 25.3 months (range: 1-59 months).
      There were no technical failures. Seventeen patients had significant improvement
      in symptoms and three had moderate improvement. The cumulative primary patency at
      1 year was 81%. One patient had no improvement (because of infrainguinal
      occlusive disease), and subsequently required femoro-popliteal bypass. There was
      no systemic morbidity within 30 days. There was 1 in-hospital death from sudden
      cardiac arrest (47 days postoperatively). Six patients died during follow-up
      (from unrelated illness). CONCLUSION: Eversion external iliac endarterectomy is
      an effective means of treating iliofemoral occlusive disease with excellent short
      term outcomes and a low complication rate in a cohort with high levels of
      comorbidity.

PMID- 20810408
TI  - Perceived support among families deciding about organ donation for their loved
      ones: donor vs nondonor next of kin.
AB  - BACKGROUND: Families' experiences in the hospital influence their decisions about
      donating organs of brain-dead relatives. Meeting families' support needs during
      this traumatic time is an obligation and a challenge for critical care staff.
      OBJECTIVES: (1) To elicit family members' accounts of various types of support
      received and perceived quality of care for themselves and their loved ones when
      they made the donation decision, and (2) to examine the relationship between
      these factors and the families' donation decision. METHODS: Retrospective
      telephone interviews of 199 families from different regions of the country were
      completed. Aside from demographic data, the survey addressed perceptions of
      informational, emotional, and instrumental support and quality of care. RESULTS:
      One hundred fifty-four study participants consented to donation; 45 declined.
      White next of kin were significantly more likely than African Americans to
      consent. Specific elements of reported support were significantly associated with
      consent to donate. Donor and nondonor families had differing perceptions of
      quality care for themselves and their loved ones. Receiving understandable
      information about organ donation was the strongest predictor of consent.
      CONCLUSIONS: Specific supportive behaviors by staff as recounted by family
      members of potential donors were significantly associated with consent to
      donation. These behaviors lend themselves to creative training and educational
      programs for staff. Such interventions are essential not only for next of kin of
      brain-dead patients, but also for staff and ultimately for the public as a whole.

PMID- 20810409
TI  - Clinical effectiveness of a critical care nursing outreach service in
      facilitating discharge from the intensive care unit.
AB  - BACKGROUND: Improved discharge planning and extension of care to the general care
      unit for patients transferring from intensive care may prevent readmission to the
      intensive care unit and prolonged hospital stays. Morbidity, mortality, and costs
      increase in readmitted intensive care patients. OBJECTIVES: To evaluate the
      clinical effectiveness of a critical care nursing outreach service in
      facilitating discharge from the intensive care unit and providing follow-up in
      general care areas. METHODS: A before-and-after study design (with historical
      controls and a 6-month prospective intervention) was used to ascertain
      differences in clinical outcomes, length of stay, and cost/benefit. Patients
      admitted to intensive care units in 3 adult teaching hospitals were recruited.
      The service centered on follow-up visits by specialist intensive care nurses who
      reviewed and assessed patients who were to be or had been discharged to general
      care areas from the intensive care unit. Those nurses also provided education and
      clinical support to staff in general care areas. RESULTS: In total, 1435 patients
      were discharged during the 6-month prospective period. Length of stay from the
      time of admission to the intensive care unit to hospital discharge (P = .85),
      readmissions during the same hospital admission (5.6% vs 5.4%, P = .83), and
      hospital survival (P = .80) did not differ from before to after the intervention.
      CONCLUSIONS: Although other studies have shown beneficial outcomes in Australia
      and the United Kingdom, we found no improvement in length of stay after admission
      to the intensive care unit, readmission rate, or hospital mortality after a
      critical care nursing outreach service was implemented.

PMID- 20810410
TI  - The medium and the message: opportunities and challenges.

PMID- 20810411
TI  - Evidence-based review and discussion points.

PMID- 20810412
TI  - Is mechanical ventilation protective just because we say so?

PMID- 20810414
TI  - Nightingale is not the best role model for today's nurses.

PMID- 20810416
TI  - Informational coping style and depressive symptoms in family decision makers.
AB  - BACKGROUND: Overwhelmed family decision makers of chronically critically ill
      patients must comprehend vital information to make complex treatment decisions
      that are consistent with patients' preferences. Exploration of informational
      coping styles of family decision makers may yield evidence for tailored
      communication practices supporting the psychological and informational needs of
      family decision makers. OBJECTIVES: To describe patterns in the demographic
      characteristics and informational coping styles of family decision makers; to
      assess differences in informational satisfaction, role stress, and depressive
      symptoms between family decision makers classified as monitors and as blunters;
      and to describe the predictive associations between informational coping styles,
      informational satisfaction, and role stress on depressive symptoms in family
      decision makers. METHODS: A secondary data analysis of 210 family decision makers
      of cognitively impaired patients who required 3 days or more of mechanical
      ventilation. On enrollment, decision makers completed the abbreviated Miller
      Behavioral Style Scale to assess informational coping styles, the Critical Care
      Family Satisfaction Survey's informational subscale to assess informational
      satisfaction, a single-item measure of role stress, and the Center for
      Epidemiological Studies Depression scale to assess depressive symptoms. RESULTS:
      No associations emerged between demographic characteristics and informational
      coping styles of family decision makers. Monitors had higher depression scores
      than did blunters. Both information coping style and informational satisfaction
      influenced depressive symptoms; however, role stress was the most significant
      predictor. CONCLUSIONS: Family decision makers classified as monitors were at
      higher risk for depression than were those who seem to avoid information.
      Targeting monitors with additional psychological and informational support may
      mitigate their psychological impairment.

PMID- 20810418
TI  - Multifactor clinical score and outcome of mechanical ventilation weaning trials:
      Burns Wean Assessment Program.
AB  - BACKGROUND: The Burns Wean Assessment Program is a 26-factor weaning assessment
      worksheet and scoring instrument used to reduce practice variability in the
      clinical management of patients receiving mechanical ventilation. The instrument
      has been tested in patients in a medical-surgical intensive care unit, but
      further testing in different populations of adult patients is needed. OBJECTIVES:
      To determine the relationship between Burns Wean Assessment Program scores and
      outcomes of weaning trials in patients treated with mechanical ventilation for 3
      or more days. METHODS: For 5 years in 5 adult critical care units (surgical,
      medical, neurological, thoracic-cardiovascular, and coronary care), advanced
      practice nurses collected scores within 24 hours of a weaning attempt. All
      patients were managed similarly by using a multidisciplinary pathway, the Burns
      Wean Assessment Program checklist, protocols for weaning trials, and sedation
      guidelines. RESULTS: Of 1889 weaning attempts, 1669 (88%) were successful, and
      220 (12%) were unsuccessful. Weaning outcomes did not differ according to sex,
      but significantly more trials were successful in younger patients than in older
      patients (P = .002) and in patients in different units (P = .01). Regardless of
      unit, patients with Burns Wean Assessment Program scores greater than 50 were
      significantly more likely to be weaned successfully (P = .001) than were patients
      with lower scores. CONCLUSIONS: Systematic tracking of the factors and scores on
      the Burns Wean Assessment Program may be helpful in care planning and management
      and in determining weaning potential.

PMID- 20810417
TI  - Communication in critical care: family rounds in the intensive care unit.
AB  - BACKGROUND: Communication with family members of patients in intensive care units
      is challenging and fraught with dissatisfaction. OBJECTIVES: We hypothesized that
      family attendance at structured interdisciplinary family rounds would enhance
      communication and facilitate end-of-life planning (when appropriate). METHODS:
      The study was conducted in the 26-bed medical intensive care unit of a tertiary
      care, academic medical center from April through October 2006. Starting in July
      2006, families were invited to attend daily interdisciplinary rounds where the
      medical team discussed the plan for care. Family members were surveyed at least 1
      month after the patient's stay in the unit, completing the validated "Family
      Satisfaction in the ICU" tool before and after implementation of family rounds.
      RESULTS: Of 227 patients enrolled, 187 patients survived and 40 died. Among
      families of survivors, participation in family rounds was associated with higher
      family satisfaction regarding frequency of communication with physicians (P =
      .004) and support during decision making (P = .005). Participation decreased
      satisfaction regarding time for decision making (P = .02). Overall satisfaction
      scores did not differ between families who attended rounds and families who did
      not. For families of patients who died, participation in family rounds did not
      significantly change satisfaction. CONCLUSIONS: In the context of this pilot
      study of family rounds, certain elements of satisfaction were improved, but not
      overall satisfaction. The findings indicate that structured interdisciplinary
      family rounds can improve some families' satisfaction, whereas some families feel
      rushed to make decisions. More work is needed to optimize communication between
      staff in the intensive care unit and patients' families, families' comprehension,
      and the effects on staff workload.

PMID- 20810419
TI  - Health care reform, health, and social justice.

PMID- 20810420
TI  - Support for families deciding about organ donation.

PMID- 20810421
TI  - Pharmacological cardiosuppression.

PMID- 20810422
TI  - Ceftriaxone-related agranulocytosis during outpatient parenteral antibiotic
      therapy.

PMID- 20810423
TI  - Targeting the chromosome partitioning protein ParA in tuberculosis drug
      discovery.
AB  - OBJECTIVE: To identify inhibitors of the essential chromosome partitioning
      protein ParA that are active against Mycobacterium tuberculosis. METHODS:
      Antisense expression of the parA orthologue MSMEG_6939 was induced on the
      Mycobacterium smegmatis background. Screening of synthetic chemical libraries was
      performed to identify compounds with higher anti-mycobacterial activity in the
      presence of parA antisense. Differentially active compounds were validated for
      specific inhibition of purified ParA protein from M. tuberculosis (Rv3918c). ParA
      inhibitors were then characterized for their activity towards M. tuberculosis in
      vitro. RESULTS: Under a number of culture conditions, parA antisense expression
      in M. smegmatis resulted in reduced growth. This effect on growth provided a
      basis for the detection of compounds that increased susceptibility to expression
      of parA antisense. Two compounds identified from library screening,
      phenoxybenzamine and octoclothepin, also inhibited the in vitro ATPase activity
      of ParA from M. tuberculosis. Structural in silico analyses predict that
      phenoxybenzamine and octoclothepin undergo interactions compatible with the
      active site of ParA. Octoclothepin exhibited significant bacteriostatic activity
      towards M. tuberculosis. CONCLUSIONS: Our data support the use of whole-cell
      differential antisense screens for the discovery of inhibitors of specific anti
      tubercular drug targets. Using this approach, we have identified an inhibitor of
      purified ParA and whole cells of M. tuberculosis.

PMID- 20810424
TI  - Preclinical advantages of intramuscularly administered peptide A3-APO over
      existing therapies in Acinetobacter baumannii wound infections.
AB  - OBJECTIVES: The designer antibacterial peptide A3-APO is efficacious in mouse
      models of Escherichia coli and Acinetobacter baumannii systemic infections. Here
      we compare the efficacy of the peptide with that of imipenem and colistin in A.
      baumannii wound infections after burn injury. METHODS: CD-1 mice were inflicted
      with burn wounds and different inocula of A. baumannii, isolated from an injured
      soldier, were placed into the wound sites. The antibiotics were given
      intramuscularly (im) one to five times. Available free peptide in the blood and
      the systemic toxicity of colistin and A3-APO were studied in healthy mice.
      RESULTS: While toxicity of colistin was observed at 25 mg/kg bolus drug
      administration, the lowest toxic dose of A3-APO was 75 mg/kg. In the A. baumannii
      blast injury models, 5 mg/kg A3-APO improved survival and reduced bacterial
      counts in the blood as well as in the wounds and improved wound appearance
      significantly better than any other antibiotic treatment. The free peptide
      concentration in the blood did not reach 1 ug/mL. CONCLUSIONS: Peptide A3-APO,
      with an intramuscular therapeutic index of 15, is more efficacious and less toxic
      than any existing burn injury infection therapy modality against multidrug
      resistant Gram-negative pathogens. A3-APO administered by the im route probably
      binds to a biopolymer that promotes the peptide's biodistribution.

PMID- 20810425
TI  - On measuring selection in experimental evolution.
AB  - Distributions of mutation fitness effects from evolution experiments are
      available in an increasing number of species, opening the way for a vast array of
      applications in evolutionary biology. However, comparison of estimated
      distributions among studies is hampered by inconsistencies in the definitions of
      fitness effects and selection coefficients. In particular, the use of ratios of
      Malthusian growth rates as 'relative fitnesses' leads to wrong inference of the
      strength of selection. Scaling Malthusian fitness by the generation time may help
      overcome this shortcoming, and allow accurate comparison of selection
      coefficients across species. For species reproducing by binary fission
      (neglecting cellular death), ln2 can be used as a correction factor, but in
      general, the growth rate and generation time of the wild-type should be provided
      in studies reporting distribution of mutation fitness effects. I also discuss how
      density and frequency dependence of population growth affect selection and its
      measurement in evolution experiments.

PMID- 20810426
TI  - Vocal cues to male androgen levels in giant pandas.
AB  - Little is known about the potential of non-human mammal vocalizations to signal
      information on the hormonal status of the caller. In the current study, we used
      endocrine data and acoustic analyses to determine whether male giant panda bleats
      provide reliable information about the caller's current androgen levels. Our
      results revealed significant relationships between acoustic features of male
      giant panda bleats and the caller's faecal androgen metabolite concentrations. To
      our knowledge, this constitutes the first demonstration that the acoustic
      structure of a non-human mammal call has the potential to yield information about
      the caller's current androgen levels. We go on to discuss the anatomical basis
      for our findings and the potential functional relevance of signalling information
      on male androgen levels in giant panda sexual communication.

PMID- 20810427
TI  - Positive selection on the killer whale mitogenome.
AB  - Mitochondria produce up to 95 per cent of the eukaryotic cell's energy. The
      coding genes of the mitochondrial DNA may therefore evolve under selection owing
      to metabolic requirements. The killer whale, Orcinus orca, is polymorphic, has a
      global distribution and occupies a range of ecological niches. It is therefore a
      suitable organism for testing this hypothesis. We compared a global dataset of
      the complete mitochondrial genomes of 139 individuals for amino acid changes that
      were associated with radical physico-chemical property changes and were
      influenced by positive selection. Two such selected non-synonymous amino acid
      changes were found; one in each of two ecotypes that inhabit the Antarctic pack
      ice. Both substitutions were associated with changes in local polarity, increased
      steric constraints and alpha-helical tendencies that could influence overall
      metabolic performance, suggesting a functional change.

PMID- 20810428
TI  - Impact of translational selection on codon usage bias in the archaeon
      Methanococcus maripaludis.
AB  - Patterns of codon usage have been extensively studied among Bacteria and
      Eukaryotes, but there has been little investigation of species from the third
      domain of life, the Archaea. Here, we examine the nature of codon usage bias in a
      methanogenic archaeon, Methanococcus maripaludis. Genome-wide patterns of codon
      usage are dominated by a strong A + T bias, presumably largely reflecting
      mutation patterns. Nevertheless, there is variation among genes in the use of a
      subset of putatively translationally optimal codons, which is strongly correlated
      with gene expression level. In comparison with Bacteria such as Escherichia coli,
      the strength of selected codon usage bias in highly expressed genes in M.
      maripaludis seems surprisingly high given its moderate growth rate. However, the
      pattern of selected codon usage differs between M. maripaludis and E. coli: in
      the archaeon, strongly selected codon usage bias is largely restricted to twofold
      degenerate amino acids (AAs). Weaker bias among the codons for fourfold
      degenerate AAs is consistent with the small number of tRNA genes in the M.
      maripaludis genome.

PMID- 20810430
TI  - Exposure to sexual signals during rearing increases immune defence in adult field
      crickets.
AB  - Increased investment in immunity is expected to be beneficial under crowded
      conditions because of the greater risk of pathogen and parasite transmission, but
      the evolution of this facultative response relies on the ability to accurately
      assess social cues in the environment and adjust immune defences accordingly.
      Because of their highly conspicuous nature, long-range sexual signals are prime
      candidates to be used in evaluating the social conditions likely to be
      experienced upon adulthood in continuously breeding species; however, their role
      in mediating immune responses is unknown. We tested whether exposure to acoustic
      sexual signals in the field cricket Teleogryllus oceanicus affects immunity by
      manipulating male juvenile experience of acoustic signals, and measuring the
      effect on adult immunity. Adult males exposed to song during rearing showed
      stronger immune responses than males reared in silence: they were better able to
      encapsulate artificial nylon implants and showed higher levels of antimicrobial
      lysozyme-like activity in their haemolymph. Experience of sexual signals thus
      translates into increased immunity, which suggests that such signals may play a
      role in conveying information about population demography and shaping density
      dependent responses in unintended receivers.

PMID- 20810431
TI  - Group decisions and individual differences: route fidelity predicts flight
      leadership in homing pigeons (Columba livia).
AB  - How social-living animals make collective decisions is currently the subject of
      intense scientific interest, with increasing focus on the role of individual
      variation within the group. Previously, we demonstrated that during paired flight
      in homing pigeons, a fully transitive leadership hierarchy emerges as birds are
      forced to choose between their own and their partner's habitual routes. This
      stable hierarchy suggests a role for individual differences mediating leadership
      decisions within homing pigeon pairs. What these differences are, however, has
      remained elusive. Using novel quantitative techniques to analyse habitual route
      structure, we show here that leadership can be predicted from prior route
      following fidelity. Birds that are more faithful to their own route when homing
      alone are more likely to emerge as leaders when homing socially. We discuss how
      this fidelity may relate to the leadership phenomenon, and propose that
      leadership may emerge from the interplay between individual route confidence and
      the dynamics of paired flight.

PMID- 20810432
TI  - Phenoloxidase but not lytic activity reflects resistance against Pasteuria ramosa
      in Daphnia magna.
AB  - The field of ecological immunology strongly relies on indicators of
      immunocompetence. Two major indicators in invertebrates, the activity of
      phenoloxidase (PO) and lytic activity have recently been questioned in studies
      showing that, across a natural range of baseline levels, these indicators did not
      predict resistance against a manipulated challenge with natural parasites. We
      confirmed this finding by showing that baseline levels of PO and lytic activity
      in the host Daphnia magna were not related to spore load of the parasite
      Pasteuria ramosa. Yet, PO levels in infected hosts did predict spore load,
      indicating PO activity can be useful as an indicator of immunocompetence in this
      model parasite-host system.

PMID- 20810434
TI  - Speciation along a depth gradient in a marine adaptive radiation.
AB  - Oceans are home to much of the world's biodiversity, but we know little about the
      processes driving speciation in marine ecosystems with few geographical barriers
      to gene flow. Ecological speciation resulting from divergent natural selection
      between ecological niches can occur in the face of gene flow. Sister species in
      the young and ecologically diverse rockfish genus Sebastes coexist in the
      northeast Pacific, implying that speciation may not require geographical
      isolation. Here, I use a novel phylogenetic comparative analysis to show that
      rockfish speciation is instead associated with divergence in habitat depth and
      depth-associated morphology, consistent with models of parapatric speciation.
      Using the same analysis, I find no support for alternative hypotheses that
      speciation involves divergence in diet or life history, or that speciation
      involves geographic isolation by latitude. These findings support the hypothesis
      that rockfishes undergo ecological speciation on an environmental gradient.

PMID- 20810433
TI  - A novel minicollagen gene links cnidarians and myxozoans.
AB  - Myxozoans are enigmatic endoparasitic organisms sharing morphological features
      with bilateria, protists and cnidarians. This, coupled with their highly
      divergent gene sequences, has greatly obscured their phylogenetic affinities.
      Here we report the sequencing and characterization of a minicollagen homologue
      (designated Tb-Ncol-1) in the myxozoan Tetracapsuloides bryosalmonae.
      Minicollagens are phylum-specific genes encoding cnidarian nematocyst proteins.
      Sequence analysis revealed a cysteine-rich domain (CRD) architecture and genomic
      organization similar to group 1 minicollagens. Homology modelling predicted
      similar three-dimensional structures to Hydra CRDs despite deviations from the
      canonical pattern of group 1 minicollagens. The discovery of this minicollagen
      gene strongly supports myxozoans as cnidarians that have radiated as
      endoparasites of freshwater, marine and terrestrial hosts. It also reveals novel
      protein sequence variation of relevance to understanding the evolution of
      nematocyst complexity, and indicates a molecular/morphological link between
      myxozoan polar capsules and cnidarian nematocysts. Our study is the first to
      illustrate the power of using genes related to a taxon-specific novelty for
      phylogenetic inference within the Metazoa, and it exemplifies how the
      evolutionary relationships of other metazoans characterized by extreme sequence
      divergence could be similarly resolved.

PMID- 20810435
TI  - Is evolutionary history repeatedly rewritten in light of new fossil discoveries?
AB  - Mass media and popular science journals commonly report that new fossil
      discoveries have 'rewritten evolutionary history'. Is this merely journalistic
      hyperbole or is our sampling of systematic diversity so limited that attempts to
      derive evolutionary history from these datasets are premature? We use two
      exemplars-catarrhine primates (Old World monkeys and apes) and non-avian
      dinosaurs-to investigate how the maturity of datasets can be assessed. Both
      groups have been intensively studied over the past 200 years and so should
      represent pinnacles in our knowledge of vertebrate systematic diversity. We test
      the maturity of these datasets by assessing the completeness of their fossil
      records, their susceptibility to changes in macroevolutionary hypotheses and the
      balance of their phylogenies through study time. Catarrhines have shown prolonged
      stability, with discoveries of new species being evenly distributed across the
      phylogeny, and thus have had little impact on our understanding of their fossil
      record, diversification and evolution. The reverse is true for dinosaurs, where
      the addition of new species has been non-random and, consequentially, their
      fossil record, tree shape and our understanding of their diversification is
      rapidly changing. The conclusions derived from these analyses are relevant more
      generally: the maturity of systematic datasets can and should be assessed before
      they are exploited to derive grand macroevolutionary hypotheses.

PMID- 20810436
TI  - Relatedness influences signal reliability in evolving robots.
AB  - Communication is an indispensable component of animal societies, yet many open
      questions remain regarding the factors affecting the evolution and reliability of
      signalling systems. A potentially important factor is the level of genetic
      relatedness between signallers and receivers. To quantitatively explore the role
      of relatedness in the evolution of reliable signals, we conducted artificial
      evolution over 500 generations in a system of foraging robots that can emit and
      perceive light signals. By devising a quantitative measure of signal reliability,
      and comparing independently evolving populations differing in within-group
      relatedness, we show a strong positive correlation between relatedness and
      reliability. Unrelated robots produced unreliable signals, whereas highly related
      robots produced signals that reliably indicated the location of the food source
      and thereby increased performance. Comparisons across populations also revealed
      that the frequency for signal production-which is often used as a proxy of signal
      reliability in empirical studies on animal communication-is a poor predictor of
      signal reliability and, accordingly, is not consistently correlated with group
      performance. This has important implications for our understanding of signal
      evolution and the empirical tools that are used to investigate communication.

PMID- 20810437
TI  - On optimal hierarchy of load-bearing biological materials.
AB  - Load-bearing biological materials such as shell, mineralized tendon and bone
      exhibit two to seven levels of structural hierarchy based on constituent
      materials (biominerals and proteins) of relatively poor mechanical properties. A
      key question that remains unanswered is what determines the number of
      hierarchical levels in these materials. Here we develop a quasi-self-similar
      hierarchical model to show that, depending on the mineral content, there exists
      an optimal level of structural hierarchy for maximal toughness of biocomposites.
      The predicted optimal levels of hierarchy and cooperative deformation across
      multiple structural levels are in excellent agreement with experimental
      observations.

PMID- 20810438
TI  - The temporal selfish herd: predation risk while aggregations form.
AB  - The hypothesis of the selfish herd has been highly influential to our
      understanding of animal aggregation. Various movement strategies have been
      proposed by which individuals might aggregate to form a selfish herd as a defence
      against predation, but although the spatial benefits of these strategies have
      been extensively studied, little attention has been paid to the importance of
      predator attacks that occur while the aggregation is forming. We investigate the
      success of mutant aggregation strategies invading populations of individuals
      using alternative strategies and find that the invasion dynamics depend
      critically on the time scale of movement. If predation occurs early in the
      movement sequence, simpler strategies are likely to prevail. If predators attack
      later, more complex strategies invade. If there is variation in the timing of
      predator attacks (through variation within or between individual predators), we
      hypothesize that groups will consist of a mixture of strategies, dependent upon
      the distribution of predator attack times. Thus, behavioural diversity can evolve
      and be maintained in populations of animals experiencing a diverse range of
      predators differing solely in their attack behaviour. This has implications for
      our understanding of predator-prey dynamics, as the timing of predator attacks
      will exert selection pressure on prey behavioural responses, to which predators
      must respond.

PMID- 20810439
TI  - How to run far: multiple solutions and sex-specific responses to selective
      breeding for high voluntary activity levels.
AB  - The response to uniform selection may occur in alternate ways that result in
      similar performance. We tested for multiple adaptive solutions during artificial
      selection for high voluntary wheel running in laboratory mice. At generation 43,
      the four replicate high runner (HR) lines averaged 2.85-fold more revolutions per
      day as compared with four non-selected control (C) lines, and females ran 1.11
      fold more than males, with no sex-by-linetype interaction. Analysis of variance
      indicated significant differences among C lines but not among HR for revolutions
      per day. By contrast, average speed varied significantly among HR lines, but not
      among C, and showed a sex-by-linetype interaction, with the HR/C ratio being 2.02
      for males and 2.45 for females. Time spent running varied among both HR and C
      lines, and showed a sex-by-linetype interaction, with the HR/C ratio being 1.52
      for males but only 1.17 for females. Thus, females (speed) and males (speed, but
      also time) evolved differently, as did the replicate selected lines. Speed and
      time showed a trade-off among HR but not among C lines. These results demonstrate
      that uniform selection on a complex trait can cause consistent responses in the
      trait under direct selection while promoting divergence in the lower-level
      components of that trait.

PMID- 20810440
TI  - Individual-learning ability predicts social-foraging strategy in house sparrows.
AB  - Social foragers can use either a 'producer' strategy, which involves searching
      for food, or a 'scrounger' strategy, which involves joining others' food
      discoveries. While producers rely on personal information and past experience, we
      may ask whether the tendency to forage as a producer is related to being a better
      learner. To answer this question, we hand-raised house sparrow (Passer
      domesticus) nestlings that upon independence were given an individual-learning
      task that required them to associate colour signal and food presence. Following
      the testing phase, all fledglings were released into a shared aviary, and their
      social-foraging tendencies were measured. We found a significant positive
      correlation between individual's performance in the individual-learning task and
      subsequent tendency to use searching (producing) behaviour. Individual-learning
      score was negatively correlated with initial fear of the test apparatus and with
      body weight. However, the correlation between individual learning and searching
      remained significant after controlling for these variables. Since it was measured
      before the birds entered a social group, individual-learning ability could not be
      the outcome of being a producer. However, the two traits may be initially
      associated, or individual learning could facilitate producing behaviour. To our
      knowledge, this is the first evidence that associates individual-learning
      abilities with social-foraging strategies in animal groups.

PMID- 20810441
TI  - A Bayesian phylogenetic approach to estimating the stability of linguistic
      features and the genetic biasing of tone.
AB  - Language is a hallmark of our species and understanding linguistic diversity is
      an area of major interest. Genetic factors influencing the cultural transmission
      of language provide a powerful and elegant explanation for aspects of the present
      day linguistic diversity and a window into the emergence and evolution of
      language. In particular, it has recently been proposed that linguistic tone-the
      usage of voice pitch to convey lexical and grammatical meaning-is biased by two
      genes involved in brain growth and development, ASPM and Microcephalin. This
      hypothesis predicts that tone is a stable characteristic of language because of
      its 'genetic anchoring'. The present paper tests this prediction using a Bayesian
      phylogenetic framework applied to a large set of linguistic features and language
      families, using multiple software implementations, data codings, stability
      estimations, linguistic classifications and outgroup choices. The results of
      these different methods and datasets show a large agreement, suggesting that this
      approach produces reliable estimates of the stability of linguistic data.
      Moreover, linguistic tone is found to be stable across methods and datasets,
      providing suggestive support for the hypothesis of genetic influences on its
      distribution.

PMID- 20810442
TI  - Spawning stock and recruitment in North Sea cod shaped by food and climate.
AB  - In order to provide better fisheries management and conservation decisions, there
      is a need to discern the underlying relationship between the spawning stock and
      recruitment of marine fishes, a relationship which is influenced by the
      environmental conditions. Here, we demonstrate how the environmental conditions
      (temperature and the food availability for fish larvae) influence the stock
      recruitment relationship and indeed what kind of stock-recruitment relationship
      we might see under different environmental conditions. Using unique zooplankton
      data from the Continuous Plankton Recorder, we find that food availability (i.e.
      zooplankton) in essence determines which model applies for the once large North
      Sea cod (Gadus morhua) stock. Further, we show that recruitment is strengthened
      during cold years and weakened during warm years. Our combined model explained 45
      per cent of the total variance in cod recruitment, while the traditional Ricker
      and Beverton-Holt models only explained about 10 per cent. Specifically, our
      approach predicts that a full recovery of the North Sea cod stock might not be
      expected until the environment becomes more favourable.

PMID- 20810443
TI  - How resource quality differentially affects motivation and ability to fight in
      hermit crabs.
AB  - Contesting animals typically gather information about the resource value and that
      information affects fight motivation. However, it is possible that particular
      resource characteristics alter the ability to fight independently of the
      motivation. Using hermit crabs, we investigate how the resource in terms of shell
      quality affects both motivation and ability to fight. These crabs fight for
      shells, but those shells have to be carried and may impose physiological costs
      that impede fight vigour. We find that the shell has different effects on
      motivation and ability. Potential attackers in very small shells were highly
      motivated to attack but, rather than having enhanced ability, unexpectedly
      quickly fatigued and subsequently were not more successful in the fights than
      were crabs in larger shells. We also examined whether defending crabs could
      gather information about the attacker's shell from the vigour of the attack.
      Defending crabs gave up quickly when a potential gain had been assessed,
      indicating that such information had been gathered. However, there was no
      indication that this could be owing to the activity of the attacker and the
      information is probably gathered via visual assessment of the shell.

PMID- 20810444
TI  - Mothers matter! Maternal support, dominance status and mating success in male
      bonobos (Pan paniscus).
AB  - Variation in male mating success is often related to rank differences. Males who
      are unable to monopolize oestrous females alone may engage in coalitions, thus
      enhancing their mating success. While studies on chimpanzees and dolphins suggest
      that coalitions are independent of kinship, information from female philopatric
      species shows the importance of kin support, especially from mothers, on the
      reproductive success of females. Therefore, one might expect a similar effect on
      sons in male philopatric species. We evaluate mating success determinants in male
      bonobos using data from nine male individuals from a wild population. Results
      reveal a steep, linear male dominance hierarchy and a positive correlation
      between dominance status and mating success. In addition to rank, the presence of
      mothers enhances the mating success of sons and reduces the proportion of matings
      by the highest ranking male. Mothers and sons have high association rates and
      mothers provide agonistic aid to sons in conflicts with other males. As bonobos
      are male-philopatric and adult females occupy high dominance status, maternal
      support extends into adulthood and females have the leverage to intervene in male
      conflicts. The absence of female support to unrelated males suggests that mothers
      gain indirect fitness benefits by supporting their sons.

PMID- 20810447
TI  - The use of lactate as a biomarker.

PMID- 20810445
TI  - Pervasive genetic associations between traits causing reproductive isolation in
      Heliconius butterflies.
AB  - Ecological speciation proceeds through the accumulation of divergent traits that
      contribute to reproductive isolation, but in the face of gene flow traits that
      characterize incipient species may become disassociated through recombination.
      Heliconius butterflies are well known for bright mimetic warning patterns that
      are also used in mate recognition and cause both pre- and post-mating isolation
      between divergent taxa. Sympatric sister taxa representing the final stages of
      speciation, such as Heliconius cydno and Heliconius melpomene, also differ in
      ecology and hybrid fertility. We examine mate preference and sterility among
      offspring of crosses between these species and demonstrate the clustering of
      Mendelian colour pattern loci and behavioural loci that contribute to
      reproductive isolation. In particular, male preference for red patterns is
      associated with the locus responsible for the red forewing band. Two further
      colour pattern loci are associated, respectively, with female mating outcome and
      hybrid sterility. This genetic architecture in which 'speciation genes' are
      clustered in the genome can facilitate two controversial models of speciation,
      namely divergence in the face of gene flow and hybrid speciation.

PMID- 20810448
TI  - Three-layer ultrasonic tissue characterization of the ventricular septum is
      predictive of prognosis in patients with non-obstructive hypertrophic
      cardiomyopathy.
AB  - AIMS: A necropsy study of patients with hypertrophic cardiomyopathy (HCM) who
      died at a young age exhibited marked disarray and fibrosis in the mid-wall layer
      of the left ventricular (LV) myocardium. We assessed ultrasonic tissue
      characteristics in the three layers of the ventricular septum (VS), and
      correlated the result with long-term prognosis in HCM. METHODS AND RESULTS: The
      magnitude of cyclic variation of integrated backscatter (CV-IB) was calculated in
      the three layers of the VS and the whole aspect of the LV posterior wall in 58
      non-obstructive HCM patients and 20 healthy controls. All HCM patients were
      prospectively followed for an average period of 7.1 years for the occurrence of
      cardiac death or hospitalization due to heart failure. Each CV-IB of four regions
      was lower in HCM patients than in controls (all P < 0.01). CV-IB of the VS mid
      wall layer was lower in 14 HCM patients with cardiac events than in patients
      without (5.4 +/- 0.6 vs. 7.4 +/- 0.5 dB, P = 0.033) although CV-IB of three other
      regions did not differ between the two groups. The optical cut-off point of %CV
      IB <90%, i.e. the ratio of CV-IB in the VS mid-wall layer to the mean value in
      the layers on both sides, was an independent predictor of cardiac events (hazard
      ratio, 6.12; 95% confidence interval, 1.62-66.6; P = 0.013), with a positive
      predictive value of 44% and particularly with a high negative predictive value of
      91%. CONCLUSION: Patients with non-obstructive HCM are not likely to undergo
      cardiac events in the near future, when the CV-IB value is not significantly
      lower in the VS mid-wall layer than in the layers on both sides.

PMID- 20810449
TI  - Analysis of left ventricular systolic function by midwall mechanics in patients
      with obstructive sleep apnoea.
AB  - AIMS: midwall mechanics reveal systolic dysfunction in obese and hypertensive
      patients with concentric left ventricular (LV) geometry, which is frequently
      detected in subjects with obstructive sleep apnoea (OSA). Midwall mechanics have
      never been studied in these patients, who frequently experience heart failure
      (HF). METHODS AND RESULTS: we analysed midwall stress-shortening relations by
      echocardiography in 150 controls and 200 patients with OSA (age 62 +/- 13 years)
      without known cardiac disease. On the basis of the severity of OSA, patients were
      divided into mild OSA (n = 63), moderate OSA (n = 70), and severe OSA (n = 67).
      LV stress-corrected midwall shortening (scMS) was considered low if <87% in men
      and <90% in women. scMS was similar in controls and mild OSA (90 +/- 13 and 91 +/
      18%, respectively) and significantly lower in moderate and severe OSA (83 +/- 14
      and 83 +/- 15%; all P < 0.001 vs. controls and mild OSA). Prevalence of low scMS
      was 40 and 39% in controls and mild OSA (P=NS), 62% in moderate and 61% in severe
      OSA (both P < 0.001 vs. controls and mild OSA). In logistic regression analysis,
      low scMS was associated with moderate-severe OSA (OR 3.82, P < 0.001) independent
      of significant associations with diabetes (OR 5.06, P < 0.01), LV hypertrophy (OR
      1.89, P = 0.01), and LV concentric geometry (OR 2.79, P < 0.001). CONCLUSION:
      midwall mechanics are impaired in more than half of middle-aged patients with OSA
      without known cardiac disease. Moderate-severe OSA predicts LV systolic
      dysfunction independent of diabetes, LV hypertrophy, and concentric geometry.
      These relations may in part explain the increased rate of HF and cardiovascular
      events in these patients.

PMID- 20810450
TI  - Changes in mitral regurgitation and left ventricular geometry during exercise
      affect exercise capacity in patients with systolic heart failure.
AB  - AIMS: exercise may dramatically change the extent of functional mitral
      regurgitation (MR) and left ventricular (LV) geometry in patients with chronic
      heart failure (CHF). We hypothesized that dynamic changes in MR and LV geometry
      would affect exercise capacity. METHODS AND RESULTS: this study included 30 CHF
      patients with functional MR who underwent symptom-limited bicycle exercise stress
      echocardiography and cardiopulmonary exercise testing for quantitative assessment
      of MR (effective regurgitant orifice; ERO), and pulmonary artery systolic
      pressure (PASP). LV sphericity index was obtained from real-time three
      dimensional echocardiograms. The patients were stratified into exercised-induced
      MR (EMR; n = 10, an increase in ERO by >=13 mm(2)) or non-EMR (NEMR; n = 20, an
      increase in ERO by <13 mm(2)) group. At rest, no differences in LV volume and
      function, ERO, and PASP were found between the two groups. At peak exercise, PASP
      and sphericity index were significantly greater (all P < 0.01) in the EMR group.
      The EMR group revealed lower peak oxygen uptake (peak VO(2); P = 0.018) and
      greater minute ventilation/carbon dioxide production slope (VE/VCO(2) slope; P =
      0.042) than the NEMR group. Peak VO(2) negatively correlated with changes in ERO
      (r = -0.628) and LV sphericity index (r = -0.437); meanwhile, VE/VCO(2) slope was
      well correlated with these changes (r = 0.414 and 0.364, respectively). A
      multivariate analysis identified that the change in ERO was the strongest
      predictor of peak VO(2) (P = 0.001). CONCLUSION: dynamic changes in MR and LV
      geometry contributed to the limitation of exercise capacity in patients with CHF.

PMID- 20810451
TI  - A retrospective study on outcome of microscopic polyangiitis in chronic renal
      replacement therapy.
AB  - BACKGROUND: Pauci-immune vasculitis is a heterogeneous disorder with an
      unfavourable prognosis. Renal involvement is frequently observed in
      antineutrophil cytoplasm autoantibody (ANCA)-associated small-vessel vasculitis
      and is an important cause of end-stage renal disease (ESRD). Renal replacement
      therapy (RRT) is frequently required. Although better prognosis under dialysis is
      well known, the long-term follow-up of pauci-immune renal vasculitis with RRT is
      rarely reported. METHODS: We described 24 patients with pauci-immune vasculitis
      and requirement of dialysis who were admitted in our institutions from January
      1989 to December 2008. Mean age was 65 +/- 12 years at the beginning of dialysis.
      There were 12 males and 12 females. Patients with Wegener's granulomatosis, Churg
      Strauss syndrome or evidence of anti-glomerular basement membrane were excluded.
      The study group was formed by patients with a diagnosis of necrotizing
      extracapillary glomerulonephritis and microscopic polyangiitis. RESULTS: The
      distribution according to ANCAs was 14 p-ANCA (58%), 5 c-ANCA (21%) and 5 ANCA
      negative (21%) pauci-immune renal vasculitis. Pulmonary renal syndrome (PRS) was
      observed in 10 patients at the onset of vasculitis. Corticosteroids and daily
      cyclophosphamide were administered to 18 patients, and one patient had
      intravenous cyclophosphamide. Five patients received isolated corticosteroid
      therapy. Early reduction in cyclophosphamide dosage was required in five patients
      due to leucopaenia. Mean follow-up after first dialysis was 89 +/- 66 months
      (range 2-208). Twenty patients were included in haemodialysis (HD), and four
      patients were included in peritoneal dialysis (PD). At the end of the study, nine
      patients had received a cadaveric kidney transplant (KT). Relapses rate after the
      onset of dialysis was 0.03 episode/patient/year. PRS-associated relapses after
      beginning dialysis were observed in four patients. Main therapy in relapses was
      also corticosteroids and cyclophosphamide. Survival rates for year 1, 2 and 5 was
      91%, 91% and 85%, respectively. Overall mortality at the end of the study was
      31.8%. Five patients died in the PRS group, but only one death was associated
      with progressive pulmonary fibrosis. Higher mortality was observed in PRS
      vasculitis present at the onset of RRT (50% vs 16.7%, P = NS). Better outcome in
      patients who received a renal transplantation was observed (88.8% vs 53.8%, P =
      NS). Conclusions. Despite a low number of patients in this series, pauci-immune
      vasculitis prognosis under dialysis seems equal to other causes of chronic kidney
      disease. This study observed a low rate of relapses after beginning dialysis.
      Poor prognosis is related to severe complications at the beginning of RRT. Today,
      kidney transplantation is an important therapeutic option for these patients.

PMID- 20810452
TI  - Parathyroid hormone-potentiated connective tissue growth factor expression in
      human renal proximal tubular cells through activating the MAPK and NF-kappaB
      signalling pathways.
AB  - BACKGROUND: Secondary hyperparathyroidism is a universal complication of chronic
      renal diseases. One of the pathological consequences of hyperparathyroidism is
      impairment of the renal interstitium and tubules. However, the molecular
      mechanism of renal tubular interstitial impairment induced by parathyroid hormone
      (PTH) remains unclear. Enhanced and prolonged expression of connective tissue
      growth factor (CTGF) has been associated with fibrosis and inflammation in the
      kidney. The purpose of this study was to investigate the effects of PTH on CTGF
      expression patterns in human proximal tubular cell line-HK-2 cells. METHODS: We
      treated cells with various concentrations of PTH for the indicated periods of
      time in the presence or absence of the mitogen-activated protein kinase (MAPK)
      inhibitor (PD98059) or the NF-kappaB inhibitor (PDTC). RESULTS: Quantitative real
      time RT-PCR analysis revealed that PTH at a concentration of 10(-12)-10(-10) M
      increased the mRNA levels of CTGF, which was similar to the trends of CTGF
      protein levels detected by immunoblotting assay. Our data clearly show the
      ability of human proximal tubular HK-2 cells to produce CTGF after the treatment
      with PTH. In addition, we showed that PTH induced the phosphorylation of MAPK p42
      and p44, and increased NF-kappaB-binding activities in the PTH-treated cells.
      Moreover, both PD98059 and PDTC inhibited the effect of PTH on the expression of
      CTGF, which strongly suggests that these pathways play important roles in the PTH
      induced CTGF upregulation in renal tubular cells. CONCLUSIONS: Our results
      indicated for the first time that PTH may enhance the expression of CTGF in human
      kidney proximal tubular cells, suggesting that PTH may play an important role in
      the fibrotic and inflammatory process that is a hallmark for progression of
      chronic kidney disease.

PMID- 20810453
TI  - Screening for encapsulating peritoneal sclerosis in patients on peritoneal
      dialysis: role of CT scanning.
AB  - BACKGROUND: We previously validated a scoring system for abdominal/pelvic CT
      scans in patients with symptomatic encapsulating peritoneal sclerosis (EPS). CT
      scans of patients with symptomatic EPS were significantly different from control
      peritoneal dialysis (PD) or haemodialysis patient scans; scans performed before
      EPS was clinically evident were near normal in 9 of 13 patients. We have now
      investigated CT scanning as a screening modality in a larger group of patients on
      long-term PD. METHODS: Pre-diagnostic CT scans performed in 20 patients for
      routine screening or other indications at least 3 months before EPS developed,
      and later diagnostic scans when EPS was clinically evident, were scored by three
      radiologists. The control group included CT scans of 20 PD patients who had not
      developed EPS (median follow-up 2.25 years). Analysis was by non-parametric
      tests. CT scores ranged from 0 to 22; > 2.5 was considered abnormal. RESULTS:
      Clinical EPS only developed after transplantation or transfer to HD. Diagnostic
      scans scored significantly higher than pre-diagnostic or control scans (median
      scores 9, 2 and 1; P < 0.001), confirming previous work. The pre-EPS diagnosis of
      12 asymptomatic patients had a median CT score = 1.75, similar to the control
      group. Eight patients had had a limited episode of abdominal symptoms (seven
      required hospitalization), but did not have the clinical picture of EPS; their
      median CT score was 4.5 (P = 0.0016 cf control group). The time from pre
      diagnostic scan to clinical EPS (median 0.82 years) and duration of PD at time of
      pre-diagnostic scan (median 7.1 years) did not differ significantly between the
      symptomatic and asymptomatic groups. CONCLUSIONS: CT screening of asymptomatic PD
      patients is not indicated; EPS may occur within a year or less of a normal CT
      scan. Abdominal symptoms in long-term PD patients can be associated with CT scan
      abnormalities; these patients are at increased risk of EPS after stopping PD.

PMID- 20810454
TI  - Programmed repression of tubular 11beta-HSD2--a novel form of AME?

PMID- 20810455
TI  - Prevention of accelerated atherosclerosis by AT1 receptor blockade in
      experimental renal failure.
AB  - BACKGROUND: The mechanisms of uraemia-induced atherosclerosis have not been fully
      delineated. The aims of this study were (i) to investigate the extent and the
      phenotype of atherosclerosis, including the activation of local renin-angiotensin
      system (RAS), in a mouse model of mild uraemia and (ii) to determine the effects
      of angiotensin II type1 (AT1) receptor blockade on the uraemic atherosclerosis,
      clarifying the mechanisms of its action. METHODS: Mild uraemia was induced by 5/6
      nephrectomy in 8-week-old apo E-deficient mice (apoE-KO). After nephrectomy, the
      animals received either treatment with candesartan or no treatment for 12-weeks.
      Sham-operated apoE-KO mice were used as controls. RESULTS: Uraemia led to a two
      fold increase in aortic plaque area. This was associated with a significant
      upregulation of aortic angiotensin-converting enzyme (ACE), AT1 receptor,
      connective tissue growth factor (CTGF), monocyte chemoattractant protein (MCP)-1
      and vascular cell adhesion molecule (VCAM)-1. Candesartan significantly reduced
      aortic atherosclerosis, prevented the upregulation of the uraemia-induced genes
      and led to changes predicting greater stability of the plaques, without
      influencing blood pressure or serum lipids. CONCLUSIONS: This study indicates
      that uraemia leads to an acceleration of aortic atherosclerosis. The upregulation
      of aortic RAS and the reduced atherosclerosis following AT1 receptor blocker
      treatment highlights the pivotal role of the local RAS in the development and
      acceleration of atherosclerosis in uraemia.

PMID- 20810456
TI  - Goodness-of-fit tests for correlated paired binary data.
AB  - We review a few popular statistical models for correlated binary outcomes,
      present maximum likelihood estimates for the model parameters, and discuss model
      selection issues using a variety of goodness-of-fit test statistics. We apply
      bootstrap strategies that are computationally efficient to evaluate the
      performance of goodness-of-fit statistics and observe that generally the power
      and the type I error rate of the goodness-of-fit statistics depend on the model
      under investigation. Our simulation results show that careful choice of goodness
      of-fit statistics is an important issue especially when we have a small sample
      and the outcomes are highly correlated. Two biomedical applications are included.

PMID- 20810457
TI  - A dose of tropical medicine.

PMID- 20810458
TI  - Satisfaction with the emergency department environment decreases with length of
      stay.
AB  - OBJECTIVE: To determine the emergency department (ED) environmental factors
      associated with patient satisfaction. METHODS: A prospective, observational study
      in a university-affiliated tertiary-referral ED and associated observation unit
      (OU). The ED environment was evaluated with a structured questionnaire, scored
      using a 100-mm visual analogue scale. Patients who stayed in the ED over 8 h
      (long-stay ED; LSED) were compared with those who stayed less than 4 h (short
      stay ED; SSED) and with a control group admitted to the OU. RESULTS: A total of
      233 patients was enrolled, overall satisfaction in SSED was 81% (95% CI 70.1 to
      88.7), 69% in LSED (95% CI 57.4 to 78.7) and 84% in OU (95% CI 73.6 to 91.0). The
      most important environmental factors were cleanliness (median importance 95,
      interquartile range (IQR) 81-98) and communication with medical staff (94, IQR 80
      98) and family (92, IQR 74-98). The least important factors were access to nature
      (38, IQR 19-65), a natural light source (50, IQR 24-74) and ability to sit out of
      bed (52, IQR 26-75). Factors rated high for importance but low for satisfaction
      were ED noise levels (median difference 40, IQR 3-70), ED trolley comfort (19,
      IQR 6-50) and food quality (12, IQR -4-29). CONCLUSION: Patients who spend over
      8&emsp14;h in the ED are less satisfied with their environment than either those
      who spend less than 4 h or patients in an OU. Importantly, distinct, amenable
      factors can be identified. These should be addressed to improve patients' overall
      ED management and satisfaction.

PMID- 20810459
TI  - Effects of script-based role play in cardiopulmonary resuscitation team training.
AB  - BACKGROUND: The purpose of this study is to compare the cardiopulmonary
      resuscitation (CPR) team dynamics and performance between a conventional
      simulation training group and a script-based training group. METHODS: This was a
      prospective randomised controlled trial of educational intervention for CPR team
      training. Fourteen teams, each consisting of five members, were recruited. The
      conventional group (C) received training using a didactic lecture and simulation
      with debriefing, while the script group (S) received training using a
      resuscitation script. The team activity was evaluated with checklists both before
      and after 1 week of training. The videotaped simulated resuscitation events were
      compared in terms of team dynamics and performance aspects. RESULTS: Both groups
      showed significantly higher leadership scores after training (C: 58.2 +/- 9.2 vs.
      67.2 +/- 9.5, p=0.007; S: 57.9 +/- 8.1 vs. 65.4 +/- 12.1, p=0.034). However,
      there were no significant improvements in performance scores in either group
      after training. There were no differences in the score improvement after training
      between the two groups in dynamics (C: 9.1 +/- 12.6 vs. S: 7.4 +/- 13.7,
      p=0.715), performance (C: 5.5 +/- 11.4 vs. S: 4.7 +/- 9.6, p=0.838) and total
      scores (C: 14.6 +/- 20.1 vs. S: 12.2 +/- 19.5, p=0.726). CONCLUSION: Script-based
      CPR team training resulted in comparable improvements in team dynamics scores
      compared with conventional simulation training. Resuscitation scripts may be used
      as an adjunct for CPR team training.

PMID- 20810460
TI  - Editorial comment.

PMID- 20810461
TI  - Strychnine poisoning: gone but not forgotten.
AB  - Strychnine was used as a pesticide until 1968 and a rodenticide until 2006 when
      its sale was banned throughout the EU and all supplies recalled. A case of
      strychnine poisoning seen in a UK emergency department in 2009 is reported to
      remind clinicians of the features and management of this increasingly rare
      presentation. Prompt recognition and early intensive supportive therapy can
      result in a favourable outcome.

PMID- 20810462
TI  - Importance of Manchester Triage in acute myocardial infarction: impact on
      prognosis.
AB  - BACKGROUND: Fast and effective diagnosis of patients with acute myocardial
      infarction (AMI) in the Emergency Department (ED) is needed. Manchester Triage
      (MT) is based on identification of the patient's main complaint, establishing,
      through decision flowcharts, a target-time for first observation. This study
      aimed to evaluate the impact of MT on short-term mortality in AMI and detect
      potential improvements, and to analyse high-risk groups: diabetic patients, women
      and older patients. METHODS: 332 consecutive patients (69.0+13.6 years mean age;
      34.9% women) with final diagnosis of AMI were assessed in the ED using MT. Data
      were analysed according to demographics and risk groups, as well as several AMI
      parameters, admission duration and intrahospital mortality (IHM). Independent
      predictors of mortality were determined. RESULTS: 82.8% of patients met the ideal
      goal of <=10 min target-time for a first observation (ITTFO). This was higher
      (95%) in typical presentations ('chest pain'), versus 52% in other flowcharts;
      p<0.01. Patients >=70 years old were less frequently screened with ITTFO <=10 min
      (76.2% vs 90.0% in those under 70; p=0.001) or the 'chest pain' flowchart (66.9%
      vs 77.5%; p=0.031). IHM was 13.3%. Triage with <=10 min ITTFO and the 'chest
      pain' algorithm seems to predict a lower mortality (0.33 OR; 95% CI 0.17 to 0.63;
      p=0.0005 and 0.49 OR; 95% CI 0.24 to 1.03; p=0.056). CONCLUSION: MT proved to be
      an effective system. Patients with typical AMI presentation, ST elevation
      myocardial infarction and less than 70 years old are protected by MT, with lower
      ITTFO and better short-term survival.

PMID- 20810463
TI  - Use of emergency oxygen in adult patients: implementing change.

PMID- 20810464
TI  - Exertional heat illness in half marathon runners: experiences of the Great North
      Run.
AB  - Exertional heat illness is a potentially fatal condition. Large numbers of
      competitors in the Great North Run are affected annually. This article briefly
      discusses the patient demographics, presentation and treatment of large numbers
      of patients with a simple, effective regime.

PMID- 20810465
TI  - Ovarian cystic teratoma torsion in pregnancy.
AB  - Acute abdominal pain during pregnancy is encountered frequently and the
      differential diagnosis is extensive. Acute ovarian torsion in a pregnant patient
      is rare and is difficult to diagnose. Infarction caused by ovarian torsion will
      result if the twist is not unwound spontaneously or surgically in a timely
      fashion. The case is described of a 28-year-old primigravida who originally
      presented to the emergency department with right lower abdominal pain. The
      patient was ultimately found to have an extremely large cystic teratoma of the
      right ovary with concomitant torsion. Bedside ultrasonography is a highly
      accessible tool that can be used in a pregnant woman for screening a mass or
      ascites. Laparoscopic surgery has now been accepted as a safe modality for
      definitive diagnosis and therapeutic intervention. Because acute ovarian torsion
      is not encountered frequently, timely diagnosis is required to prevent mortality
      and minimise morbidity. It is important to keep ovarian torsion in the
      differential diagnosis of any pregnant woman with acute abdominal pain. Emergency
      physicians should be aware of the possibility of acute ovarian torsion in
      pregnant women and should have a high index of suspicion. Early surgical
      intervention should be undertaken.

PMID- 20810466
TI  - Maternal alcohol consumption, alcohol metabolism genes, and the risk of oral
      clefts: a population-based case-control study in Norway, 1996-2001.
AB  - Heavy maternal alcohol consumption during early pregnancy increases the risk of
      oral clefts, but little is known about how genetic variation in alcohol
      metabolism affects this association. Variants in the alcohol dehydrogenase 1C
      (ADH1C) gene may modify the association between alcohol and clefts. In a
      population-based case-control study carried out in Norway (1996-2001), the
      authors examined the association between maternal alcohol consumption and risk of
      oral clefts according to mother and infant ADH1C haplotypes encoding fast or slow
      alcohol-metabolizing phenotypes. Subjects were 483 infants with oral cleft
      malformations and 503 control infants and their mothers, randomly selected from
      all other livebirths taking place during the same period. Mothers who consumed 5
      or more alcoholic drinks per sitting during the first trimester of pregnancy had
      an elevated risk of oral cleft in their offspring (odds ratio (OR) = 2.6, 95%
      confidence interval (CI): 1.4, 4.7). This increased risk was evident only in
      mothers or children who carried the ADH1C haplotype associated with reduced
      alcohol metabolism (OR= 3.0, 95% CI: 1.4, 6.8). There was no evidence of alcohol
      related risk when both mother and infant carried only the rapid-metabolism ADH1C
      variant (OR = 0.9, 95% CI: 0.2, 4.1). The teratogenic effect of alcohol may
      depend on the genetic capacity of the mother and fetus to metabolize alcohol.

PMID- 20810467
TI  - Enhancing deaf students' learning from sign language and text: metacognition,
      modality, and the effectiveness of content scaffolding.
AB  - Four experiments, each building on the results of the previous ones, explored the
      effects of several manipulations on learning and the accuracy of metacognitive
      judgments among deaf and hard-of-hearing (DHH) students. Experiment 1 examined
      learning and metacognitive accuracy from classroom lectures with or without prior
      scaffolding in the form of a description of main points and concepts. Experiment
      2 compared the benefits of scaffolding when material was read versus when it was
      presented as a lecture signed for DHH students and spoken for hearing students.
      Experiment 3 compared scaffolding provided in the form of main points versus
      vocabulary, and Experiment 4 examined effects of material familiarity and a delay
      between study and test. Results indicated that although all students had a
      tendency to overestimate their performance, hearing students learned more and
      were more accurate in their metacognitive judgments than DHH students. Content
      familiarity improved the accuracy of metacognitive judgments by both DHH and
      hearing students, but the delay manipulation was effective only for hearing
      students. Consistent with other recent findings, DHH students learned as much
      from reading as they did from signed instruction. Differences between DHH and
      hearing students may indicate the need for explicit instruction for DHH students
      in academically relevant skills acquired incidentally by hearing students.

PMID- 20810468
TI  - Rapid microsatellite development for water striders by next-generation
      sequencing.
AB  - Water striders have become a model system for studies of sexual conflict and
      coevolution, but progress is currently limited by a lack of genetic resources.
      Next-generation sequencing technologies offer the potential for rapid and cost
      effective development of molecular markers and hold particular promise for model
      organisms in ecology for which no reference genome exists. We used Roche 454
      sequencing of genomic DNA to identify microsatellite loci for the water strider
      Gerris incognitus. A modest sequencing volume generated 182,912 reads, of which
      30,820 (16.8%) contained microsatellite repeats. We selected 23 loci for primer
      development, based on criteria that maximized the likelihood of amplifying
      polymorphic loci, and tested them in G. incognitus and the related species G.
      buenoi. Of the 16 amplifying loci, 10 yielded reliable amplification and
      detectable polymorphism, with an average of 6.1 alleles per locus (range: 2-12).
      These markers should facilitate new avenues of study, including postcopulatory
      sexual selection, population genetic structure, phylogeography, and sexual
      coevolution, for a key taxon in studies of mating conflict. The current study
      demonstrates an effective method for microsatellite development and shows that
      light sequencing of genomic DNA can provide numerous and highly variable markers.

PMID- 20810470
TI  - Impact of co-occurring posttraumatic stress disorder on suicidal women with
      borderline personality disorder.
AB  - OBJECTIVE: The authors examined the impact of co-occurring posttraumatic stress
      disorder (PTSD) on women with borderline personality disorder who had attempted
      suicide in the preceding year. METHOD: Female borderline personality disorder
      outpatients (N=94) either with (N=53, 56.4%) or without PTSD (N=41, 43.6%) and
      with recent and repeated suicidal or self-injurious behavior were compared in
      nine areas of functioning. RESULTS: Borderline personality disorder patients with
      and without PTSD differed in the lethality, intent, and triggers for intentional
      self-injury, trauma history, emotion regulation, and axis I comorbidity. The two
      groups did not differ in borderline personality disorder severity, axis II
      comorbidity, psychosocial functioning, or mental health or medical treatment
      utilization. CONCLUSIONS: The results indicate greater impairment among
      individuals with both disorders and suggest that there are some unique features
      associated with co-occurring borderline personality disorder and PTSD that
      require further attention in assessment and treatment.

PMID- 20810469
TI  - Modafinil reverses phencyclidine-induced deficits in cognitive flexibility,
      cerebral metabolism, and functional brain connectivity.
AB  - OBJECTIVE: In the present study, we employ mathematical modeling (partial least
      squares regression, PLSR) to elucidate the functional connectivity signatures of
      discrete brain regions in order to identify the functional networks subserving
      PCP-induced disruption of distinct cognitive functions and their restoration by
      the procognitive drug modafinil. METHODS: We examine the functional connectivity
      signatures of discrete brain regions that show overt alterations in metabolism,
      as measured by semiquantitative 2-deoxyglucose autoradiography, in an animal
      model (subchronic phencyclidine [PCP] treatment), which shows cognitive
      inflexibility with relevance to the cognitive deficits seen in schizophrenia.
      RESULTS: We identify the specific components of functional connectivity that
      contribute to the rescue of this cognitive inflexibility and to the restoration
      of overt cerebral metabolism by modafinil. We demonstrate that modafinil reversed
      both the PCP-induced deficit in the ability to switch attentional set and the PCP
      induced hypometabolism in the prefrontal (anterior prelimbic) and retrosplenial
      cortices. Furthermore, modafinil selectively enhanced metabolism in the medial
      prelimbic cortex. The functional connectivity signatures of these regions
      identified a unifying functional subsystem underlying the influence of modafinil
      on cerebral metabolism and cognitive flexibility that included the nucleus
      accumbens core and locus coeruleus. In addition, these functional connectivity
      signatures identified coupling events specific to each brain region, which relate
      to known anatomical connectivity. CONCLUSIONS: These data support clinical
      evidence that modafinil may alleviate cognitive deficits in schizophrenia and
      also demonstrate the benefit of applying PLSR modeling to characterize functional
      brain networks in translational models relevant to central nervous system
      dysfunction.

PMID- 20810471
TI  - The hippocampal formation in schizophrenia.
AB  - The hippocampal formation is one of the most extensively studied regions of the
      brain, with well-described anatomy and basic physiology; moreover, aspects of
      human memory mediated by the hippocampus are well characterized. In
      schizophrenia, alterations in hippocampal anatomy, perfusion, and activation are
      consistently reported; impairments in declarative memory function, especially in
      the flexible use of event memories (e.g., in the service of memory-based
      inference), are common. Postmortem molecular changes suggest a selective
      reduction in glutamate transmission in the dentate gyrus and in its efferent
      fibers, the mossy fiber pathway. A reduction in dentate gyrus glutamatergic
      output and in its information processing functions could generate two co
      occurring outcomes in the hippocampus: 1) a change in homeostatic plasticity
      processes in cornu ammonis 3 (CA3), accompanied by increased activity due to
      reduced afferent stimulation from the dentate gyrus onto CA3 neurons, a process
      that could increase the pattern completion functions of CA3, and 2) the loss of
      mnemonic functions specific to the dentate gyrus, namely pattern separation, a
      change that could increase the prevalence of illusory pattern completion and
      reduce discrimination between present and past experiences in memory. The
      resulting increase in "runaway" CA3-mediated pattern completion could result in
      cognitive "mistakes," generating psychotic associations and resulting in memories
      with psychotic content. Tests of this model could result in novel approaches to
      the treatment of psychosis and declarative memory alterations and in novel animal
      preparations for basic schizophrenia research.

PMID- 20810472
TI  - Altering the trajectory of anxiety in at-risk young children.
AB  - OBJECTIVE: Increasing evidence for the importance of several risk factors for
      anxiety disorders is beginning to point to the possibility of prevention. Early
      interventions targeting known risk for anxiety have rarely been evaluated. The
      authors evaluated the medium-term (3-year) effects of a parent-focused
      intervention for anxiety in inhibited preschool-age children. METHOD: The study
      was a randomized controlled trial of a brief intervention program provided to
      parents compared with a monitoring-only condition. Participants were 146
      inhibited preschool-age children and their parents; data from two or more
      assessment points were available at 3 years for 121 children. Study inclusion was
      based on parent-reported screening plus laboratory-observed inhibition. The six
      session group-based intervention included parenting skills, cognitive
      restructuring, and in vivo exposure. The main outcome measures were number and
      severity of anxiety disorders, anxiety symptoms, and extent of inhibition.
      RESULTS: Children whose parents received the intervention showed lower frequency
      and severity of anxiety disorders and lower levels of anxiety symptoms according
      to maternal, paternal, and child report. Levels of inhibition did not differ
      significantly based on either parent report or laboratory observation.
      CONCLUSIONS: This brief, inexpensive intervention shows promise in potentially
      altering the trajectory of anxiety and related disorders in young inhibited
      children.

PMID- 20810473
TI  - Parenteral administration of recombinant human neuregulin-1 to patients with
      stable chronic heart failure produces favourable acute and chronic haemodynamic
      responses.
AB  - AIMS: Neuregulin-1 (NRG-1) plays a critical role in the adaptation of the heart
      to injury, inhibiting apoptosis and inducing cardiomyocyte proliferation. We have
      shown previously that rhNRG-1 improves cardiac function and survival in animal
      models of cardiomyopathy. Here we report the first human study aimed at exploring
      the acute and chronic haemodynamic responses to recombinant human NRG-1 (beta(2a)
      isoform; rhNRG-1) in patients with stable chronic heart failure (CHF). METHODS
      AND RESULTS: Fifteen patients (age, 60 +/- 2; NYHA II:III, 9:6; left ventricular
      ejection fraction (LVEF) <40%) on optimal medical therapy for CHF, received a
      rhNRG-1 infusion daily for 11 days. Acute and chronic haemodynamic, structural
      and biochemical effects were determined by serial right heart catheterization,
      cardiac magnetic resonance (CMR), echocardiography and measurement of
      neurohumoral indices. Acutely, cardiac output increased by 30% during a 6 h rhNRG
      1 infusion (P < 0.01). Pulmonary artery wedge pressure and systemic vascular
      resistance decreased 30 and 20%, respectively, at 2 h (P < 0.01). A 47% reduction
      in serum noradrenaline, a 55% reduction in serum aldosterone and a 3.6-fold
      increase in N-terminal prohormone brain natriuretic peptide levels were
      concurrently observed (P < 0.001). These acute haemodynamic effects were
      sustained, as demonstrated by the 12% increase in LVEF from 32.2 +/- 2.0%
      (baseline) to 36.1 +/- 2.3% (mean +/- SE, P < 0.001) at 12 weeks. The therapy was
      well tolerated. CONCLUSION: rhNRG-1 appears to produce favourable acute and
      chronic haemodynamic effects in patients with stable CHF on optimal medical
      therapy. Randomized controlled trials of rhNRG-1 in cardiac disease are thus
      warranted. Clinical Trial Registration Information The trial was registered with
      the Australian New Zealand Clinical Trials Registry, anzctr.org.au Identifier:
      ACTRN12607000330448.

PMID- 20810474
TI  - Possible benefit of cardiac resynchronization therapy with ejection fraction
      >35%.

PMID- 20810476
TI  - Oil, health, and health care.

PMID- 20810480
TI  - Persistent Baltic cough.

PMID- 20810482
TI  - Prevalence and incidence.

PMID- 20810484
TI  - The Commonwealth games and "Delhi belly": what India can learn from LA.

PMID- 20810494
TI  - Growing trend of China's contribution to the field of rheumatology 2000-2009: a
      survey of Chinese rheumatology research.
AB  - OBJECTIVE: In the past decade, rheumatology in China has achieved great advances.
      However, scientific publications on rheumatology in the 3 major regions of China 
      Mainland (ML), Hong Kong (HK), and Taiwan (TW) - are unknown. We assessed the
      performance of rheumatology research in China from 2000 to 2009. METHODS: Twenty
      two journals included in the rheumatology category of the Journal Citation
      Reports database were selected. We analyzed the following measures for 2000-2009:
      (1) total number of articles originating from ML, HK, and TW; (2) impact factor
      (IF) of those articles; (3) total number of citations and average number of
      citations per article; and (4) number of articles about clinical trials,
      randomized controlled trials (RCT), and case reports. We also noted the total
      number of articles from the 3 regions published in 10 top-ranking journals.
      RESULTS: There were 788 articles for the 3 regions of China, including 259 from
      ML, 372 from TW, and 157 from HK, with a positive trend between the years 2000 to
      2009. From 2006 on, published articles from ML exceeded those from HK, and in
      2008, published articles from ML exceeded those from TW. HK had the highest
      average IF and highest average citations of each article compared with articles
      from ML and TW. TW published the most RCT, clinical trials, and case reports, as
      well as the most articles in the 10 top-ranking journals in the last decade,
      followed by ML and HK. CONCLUSION: Chinese contributions to the field of
      rheumatology have increased rapidly since 2000, particularly from ML. HK had the
      highest quality research output according to average IF and average citations per
      article.

PMID- 20810495
TI  - Power Doppler ultrasonography assessment of entheses in spondyloarthropathies:
      response to therapy of entheseal abnormalities.
AB  - OBJECTIVE: To investigate the response to therapy of entheseal abnormalities
      assessed with power Doppler (PD) ultrasound (US) in spondyloarthropathies (SpA).
      METHODS: A total of 327 patients with active SpA who were starting anti-tumor
      necrosis factor (TNF) therapy were prospectively recruited at 35 Spanish centers.
      A PDUS examination of 14 peripheral entheses was performed by the same
      investigator in each center at baseline and at 6 months. The following elementary
      lesions were assessed at each enthesis (presence/absence): morphologic
      abnormalities (hypoechogenicity and/or thickening), entheseal calcific deposits,
      cortical abnormalities (bone erosion and/or proliferation), adjacent bursitis and
      intraenthesis and perienthesis (tendon body and/or bursa) PD signal. Response to
      therapy of each elementary lesion was assessed by calculating change in the
      cumulative presence from baseline to 6 months. Intraobserver reliability of PDUS
      was evaluated by blindly assessing the stored baseline images 3 months after the
      real-time examination. RESULTS: Complete data were obtained on 197 patients who
      received anti-TNF therapy for 6 months. In 91.4% of the patients there were gray
      scale or PD elementary lesions at baseline and at 6 months. Cumulative entheseal
      morphologic abnormalities, intraenthesis PD, perienthesis PD, and bursitis showed
      a significant decrease from baseline to 6 months (p < 0.05). There was high
      intraobserver reliability for all elementary lesions (interclass correlation
      coefficient > 0.90, p < 0.0005). CONCLUSION: Entheseal morphologic abnormalities,
      PD signal, and bursitis were US abnormalities that were responsive to anti-TNF
      therapy in SpA. PDUS can be a reproducible method for multicenter monitoring of
      therapeutic response in enthesitis of SpA.

PMID- 20810496
TI  - Clinical manifestations but not cytokine profiles differentiate adult-onset
      Still's disease and sepsis.
AB  - OBJECTIVE: To analyze clinical manifestations, serum ferritin, and serum cytokine
      levels in patients with adult-onset Still's disease (AOSD) or bacterial sepsis
      and to evaluate their potential use for differential diagnosis. METHODS: Twenty
      two consecutive patients with the first flare of AOSD and 6 patients with an
      established diagnosis of AOSD under immunosuppressive therapy were compared with
      14 patients with bacterial sepsis. Clinical manifestations were scored in a
      Pouchot AOSD activity score including elevated serum ferritin levels to obtain a
      modified Pouchot score. Serum cytokine profiles were analyzed from each patient.
      RESULTS: The scores of clinical manifestations using a modified Pouchot activity
      score were significantly higher in patients with active untreated AOSD (mean 5.60
      +/- 1.93) compared with patients with chronic AOSD (mean 1.16 +/- 0.98; p <
      0.001) and patients with sepsis (mean 2.38 +/- 1.19; p < 0.001). A modified
      Pouchot score >= 4 shows a sensitivity of 92% and a specificity of 93% for active
      AOSD. Serum cytokine levels of interleukin 1beta (IL-1beta), IL-6, IL-8, IL-10,
      IL-12, IL-18, interferon-gamma, tumor necrosis factor-alpha, and calprotectin
      were elevated in acute AOSD and sepsis. Significant differences were detected
      only in patients with sepsis who had higher levels of IL-6 and IL-8. The overlap
      of the 2 groups limits the use of cytokines for differential diagnosis in
      individual patients. CONCLUSION: A modified Pouchot AOSD activity score including
      elevated serum ferritin levels was more useful to confirm the diagnosis of AOSD
      compared to patients with sepsis. Elevated serum cytokines correlate with
      inflammation but are of limited use to differentiate between active AOSD and
      bacterial sepsis.

PMID- 20810497
TI  - Predicting the longer-term outcomes of total hip replacement.
AB  - OBJECTIVE: The objective of this study was to identify the patient-level
      predictors (age, sex, body mass index, mental health, and comorbidity) for a
      sustained functional outcome at a minimum 1 year of followup after total hip
      replacement (THR). METHODS: We reviewed data from our registry on 636 consecutive
      patients from 1998 to 2005. Demographic data and the outcome scores of the
      Western Ontario McMaster University Osteoarthritis Index (WOMAC) and Medical
      Outcomes Study Short-form 36 (SF-36) scores were extracted from the database.
      Longitudinal regression modeling was performed to identify the predictive factors
      of interest. Fourteen percent of patients were missing outcomes data at 1 year of
      followup. RESULTS: The mean followup in our cohort was 3.3 years (range 1-6 yrs)
      and there were no revisions for aseptic loosening performed during this time.
      Mean clinical outcome scores were found to be relatively constant for the 6 years
      after surgery. Older age, year of followup, and greater comorbidity were
      identified as negative prognostic factors for a sustained functional outcome
      following THR (p < 0.05). CONCLUSION: Understanding of longterm surgical outcomes
      should be appropriately used to set realistic patient expectations of surgery.

PMID- 20810498
TI  - Pharmacologic immunomodulation and cutaneous malignancy in rheumatoid arthritis,
      psoriasis, and psoriatic arthritis.
AB  - OBJECTIVE: It is unclear if skin cancer risk is affected by the use of
      immunomodulatory medications in rheumatoid arthritis (RA), psoriasis, and
      psoriatic arthritis (PsA). The purpose of this study is to evaluate and summarize
      the available data pertinent to this question. METHODS: The English language
      literature on PubMed was searched with a combination of phrases, including
      "malignancy," "skin cancer," "squamous cell carcinoma," "basal cell carcinoma,"
      "melanoma," "psoriasis," "psoriatic arthritis," and "rheumatoid arthritis" in
      addition to the generic names of a variety of common immunomodulatory drugs.
      Relevant articles were identified and data were extracted. RESULTS: In total,
      2218 potentially relevant articles were identified through the search process.
      After further screening, 20 articles relevant to RA were included. An additional
      19 articles relevant to either psoriasis or PsA were included as well. RA may be
      a risk factor for the development of cutaneous malignancy. Treatment with tumor
      necrosis factor inhibitors increases the rates of non-melanoma skin cancer (NMSC)
      in RA and psoriasis. This risk doubles when combination methotrexate therapy is
      used in RA. Methotrexate may increase the risk of malignant melanoma in patients
      with RA and the risk of NMSC in psoriasis. Cyclosporine and prior phototherapy
      significantly increase the risk of NMSC. CONCLUSION: RA may potentiate the risk
      of cutaneous malignancy and therefore dermatologic screening in this population
      should be considered. The use of immunomodulatory therapy in RA, psoriasis, and
      PsA may further increase the risk of cutaneous malignancy and therefore
      dermatologic screening examinations are warranted in these groups. More careful
      recording of skin cancer development during clinical trials and cohort studies is
      necessary to further delineate the risks of immunomodulatory therapy.

PMID- 20810499
TI  - Detection and functional evaluation of -262A/T and -188A/G polymorphisms of SLAM
      gene in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: Signaling lymphocytic activation molecule (SLAM) has been related to
      the pathology of systemic lupus erythematosus (SLE) through regulation of T cell
      dependent humoral immune responses. We investigated the functional associations
      of the -262A/T and -188A/G polymorphisms of SLAM in Chinese patients with SLE.
      METHODS: Genotyping of -262A/T (rs2295614) and -188A/G (rs2295613) in SLAM was
      carried out in 248 cases and 278 controls. Promoter activities of haplotypes on
      the SLAM gene were evaluated with the dual-luciferase reporter system. The mRNA
      expressions of SLAM on peripheral blood mononuclear cells (PBMC) of SLE patients
      with different genotypes were determined by real-time polymerase chain reaction.
      RESULTS: Frequencies of -262A allele and -188G allele were significantly higher
      in SLE patients than in controls. Haplotype analysis and multifactorial logistic
      regression analysis showed that individuals with the AG/AG haplotype had
      increased susceptibility to SLE (p = 0.002, OR 1.478, 95% CI 1.152-1.897). In
      response to PHA stimulation, the SLAM mRNA expression on PBMC of SLE patients was
      significantly higher in -262A-188G haplotype homozygotes compared with -262A-188G
      heterozygotes and individuals with other genotypes. CONCLUSION: Our findings
      suggest that -262A-188G haplotype in the SLAM gene promoter contributes to the
      risk of SLE by increasing the expression of SLAM.

PMID- 20810500
TI  - The LupusQoL and associations with demographics and clinical measurements in
      patients with systemic lupus erythematosus.
AB  - OBJECTIVE: Having developed and validated a disease-specific health-related
      quality of life (HRQOL) measure for patients with systemic lupus erythematosus
      (SLE), the LupusQoL, we determined its relationship to demographic and clinical
      measurements in a group of patients with SLE. METHODS: A group of 322 outpatients
      completed the LupusQoL. Demographic (age, sex, marital status, ethnicity) and
      clinical variables (disease duration, disease activity, damage) were recorded.
      Associations between the 8 LupusQoL domains and age, disease duration, disease
      activity, and damage were explored using Spearman's correlation coefficients.
      Differences in LupusQoL scores were examined for sex and marital status using the
      Mann-Whitney U test. Ethnic groups were compared using ANOVA. RESULTS: All
      domains of LupusQoL were impaired, with fatigue (56.3) being the worst affected
      and body image (80.0) the least. The correlations between the LupusQoL domain
      scores and age (r = -0.01 to -0.22) and disease duration (r = 0 to 0.16) were
      absent or weak. Similarly, there were no significant differences in the LupusQoL
      scores regarding sex, marital status, or the 3 main ethnic groups (Black
      Caribbean, Asian, White). Although there were statistically significant
      correlations between the scores of the LupusQoL domains and some scores of the
      British Isles Lupus Assessment Group index (r = -0.22 to 0.09) and the Systemic
      Lupus International Collaborating Clinics/American College of Rheumatology Damage
      Index (r = -0.29 to 0.21), these were weak. CONCLUSION: HRQOL was impaired in
      this cohort of outpatients with SLE as assessed by the validated lupus-specific
      LupusQoL. There were no clinically important associations between the 8 domains
      of the LupusQoL and clinical or demographic variables in this group of patients.
      Thus, the LupusQoL is a relatively independent outcome measure in patients with
      SLE.

PMID- 20810501
TI  - Limited value of temporal artery ultrasonography examinations for diagnosis of
      giant cell arteritis: analysis of 77 subjects.
AB  - OBJECTIVE: Use of TA-US for diagnostic investigation of giant cell arteritis
      (GCA) has been proposed but remains a matter of debate because of the
      heterogeneous findings. We retrospectively evaluated operating characteristics of
      temporal artery ultrasonography (TA-US) in a single teaching hospital. METHODS:
      All subjects with suspected GCA had been seen between 2002 and 2008 and had
      undergone TA-US with continuous-wave Doppler (until 2004) or color duplex
      ultrasonography (after 2004), followed within 30 days by a temporal artery biopsy
      (TAB). TA-US findings were compared with TAB-proven GCA and clinically diagnosed
      GCA. Results are expressed as sensitivities, specificities, and positive (LR+)
      and negative likelihood ratios (LR-) of stenoses, occlusions, and the halo sign;
      for the latter, only color duplex TA-US was considered. RESULTS: Seventy-seven
      patients fulfilled the selection criteria; 13 had TAB-proven and 19 had
      clinically defined GCA. Stenoses/occlusions were seen on 45.5% of TA-US and the
      halo sign was seen only once (3.2%) in 31 duplex TA-US. Respective sensitivities,
      specificities, LR+, and LR- for GCA diagnosis (using TAB-proven/clinically
      defined GCA as reference standards) were 69%/53%, 59%/57%, 1.7/1.2, and 0.5/0.8
      for stenoses and/or occlusions, and 17%/10%, 100%/100%, infinite/infinite, and
      0.8/0.9 for the halo sign. CONCLUSION: The halo sign showed 100% specificity for
      GCA but only 10%-17% sensitivity. Stenoses/occlusions were of low diagnostic
      value. These observations suggest that TA-US is neither an effective substitute
      for TAB nor a reliable screening test to decide which patients can be safely
      spared TAB.

PMID- 20810502
TI  - Impaired gastric emptying in primary Sjogren's syndrome.
AB  - OBJECTIVE: To investigate the prevalence of impaired gastric emptying (IGE) and
      its relation to autonomic nervous dysfunction (AD), functional bowel syndrome,
      and inflammatory and serological variables in patients with primary Sjogren's
      syndrome (pSS). METHODS: Twenty-eight patients with pSS according to the American
      European Consensus Criteria were included in the study. Gastric emptying was
      evaluated by the octanoate breath test from which half-time (t(half)) and lag
      time (t(lag)) were determined and compared with the results from 50 healthy
      controls. Autonomic nervous function was evaluated by 5 objective autonomic
      reflex tests (ART) and by the Autonomic Symptom Profile (ASP) questionnaire
      evaluating AD symptoms. These results were compared with previously investigated
      healthy ART controls and population-based ASP controls. Patients were also
      assessed regarding symptoms of functional bowel syndrome. RESULTS: The t(half)
      and the t(lag) were significantly prolonged in patients compared to controls.
      Forty-three percent of patients with pSS presented signs of IGE and 29% fulfilled
      the criteria for gastroparesis. Significant correlations were found between
      t(lag) and increased levels of IgG (p = 0.02) and erythrocyte sedimentation rate
      (ESR; p = 0.01). In addition, rheumatoid factor (RF) seropositives showed
      objective signs of IGE to a greater extent than RF seronegatives. No associations
      between IGE, ART variables, ASP variables, or gastrointestinal symptoms were
      found. CONCLUSION: IGE was common in pSS. Associations with inflammatory and
      serological features of pSS could imply immunological mechanisms behind the IGE.
      Objective signs of IGE were not associated with objective signs or subjective
      symptoms of AD or functional bowel syndrome.

PMID- 20810503
TI  - Deterioration of heart rate recovery index in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disorder resulting
      in multisystemic inflammatory damage. It is reported that cardiovascular diseases
      (CVD) are responsible for 20%-30% of deaths in patients with SLE. Heart rate
      recovery after exercise is a function of vagal reactivation, and its impairment
      is an independent prognostic indicator for cardiovascular and all-cause
      mortality. The aim of our study was to evaluate the heart rate recovery index in
      patients with SLE. METHODS: The study population included 48 patients with SLE
      (35 women, mean age 46.3 +/- 12.8 yrs, mean disease duration 6.0 +/- 2.3 yrs) and
      44 healthy controls (30 women, mean age 45.7 +/- 12.9 yrs). Basal
      electrocardiography, echocardiography, and treadmill exercise testing were
      performed on all patients and controls. The heart rate recovery index was defined
      as the reduction in the heart rate from the rate at peak exercise to the rate at
      the first minute (HRR(1)), second minute (HRR(2)), third minute (HRR(3)), and
      fifth minute (HRR(5)) after stopping exercise stress testing. RESULTS: There were
      significant differences in HRR(1) and HRR(2) indices between patients with SLE
      and the control group (24.1 +/- 6.5 vs 33.3 +/- 9.3; p < 0.001, and 44.6 +/- 13.3
      vs 53.7 +/- 9.9; p < 0.001, respectively). Similarly, HRR(3) and HRR(5) indices
      of the recovery period were lower in patients with SLE, compared with indices in
      the control group (57.6 +/- 13.0 vs 64.9 +/- 11.7; p = 0.006, and 67.2 +/- 12.3
      vs 75.0 +/- 15.4; p = 0.009, respectively). Effort capacity was markedly lower
      (9.0 +/- 1.9 vs 11.1 +/- 2.3 metabolic equivalents; p = 0.001, respectively)
      among the patients with SLE. CONCLUSION: The heart rate recovery index is
      deteriorated in patients with SLE. When the prognostic significance of the heart
      rate recovery index is considered, these results may contribute to explain the
      increased occurrence of cardiac death. It points to the importance of the heart
      rate recovery index in the identification of high-risk patients.

PMID- 20810504
TI  - Association of the intergenic single-nucleotide polymorphism rs10865331 (2p15)
      with ankylosing spondylitis in a Spanish population.
AB  - OBJECTIVE: A recent genome-wide association study has identified 2 single
      nucleotide polymorphisms (SNP) associated with ankylosing spondylitis (AS),
      rs10865331 (2p15) and rs2242944 (21q22). We assessed the association of these SNP
      with AS in a Spanish population. METHODS: Four hundred fifty-six patients with AS
      fulfilling the modified New York Criteria and 300 healthy donors were analyzed.
      Result. SNP rs10865331 (allele A: p = 0.039; genotype: p = 0.016) was
      significantly associated with AS, while no association was found for rs2242944.
      CONCLUSION: This is the first study that replicates in an independent cohort the
      association of the intergenic SNP rs10865331 with susceptibility to AS.

PMID- 20810505
TI  - Prevalence of pulmonary hypertension in systemic sclerosis in European Caucasians
      and metaanalysis of 5 studies.
AB  - OBJECTIVE: To measure the prevalence of different types of pulmonary hypertension
      (PH) and to identify patients with systemic sclerosis (SSc) at highest risk in a
      multicenter European sample, with a metaanalysis of relevant studies. METHODS:
      Consecutive patients with SSc recruited at 11 French and Italian centers
      underwent detailed evaluations, including Doppler echocardiography, chest
      computed tomography, pulmonary function tests, and right-heart catheterization
      (RHC), to detect the presence and causes of PH. A metaanalysis was performed,
      including data from 4 other studies. RESULTS: Among 206 patients in whom it was
      suspected, PH was confirmed by RHC in 83 patients (7%). Precapillary PH was found
      in 64 patients (5%), of whom 42 had pulmonary arterial hypertension (PAH) and 22
      had PH secondary to interstitial lung disease (ILD). RHC identified 17 patients
      (1%) with postcapillary PH secondary to left-heart disease. Patients with
      DLCO/alveolar volume < 70% were more likely to have precapillary PH (87.5% vs
      42%; p < 0.0001). Precapillary and postcapillary PH were associated with advanced
      age (68 +/- 14 vs 59 +/- 12 yrs, p < 0.0001, and 74 +/- 16 vs 61.5 +/- 10 yrs, p
      < 0.0001, respectively). The metaanalysis of 3818 patients showed a prevalence of
      precapillary PH of 9% (95% CI 6%-12%) and identified advanced age, longer disease
      duration, and limited cutaneous disease subset as risk factors for this
      condition. CONCLUSION: The prevalence of precapillary PH in our multicenter study
      of SSc was 5%, and in the metaanalysis 9%. Our observations support use of RHC to
      confirm the presence of precapillary PH suspected by noninvasive testing. We also
      identified patients at high risk who should be carefully monitored.

PMID- 20810506
TI  - The association between disease activity and duration in systemic sclerosis.
AB  - OBJECTIVE: The absence of a standardized disease activity index has been an
      important barrier in systemic sclerosis (SSc) research. We applied the newly
      derived Valentini Scleroderma Disease Activity Index (SDAI) among our cohort of
      patients with SSc to document changes in disease activity over time and to assess
      possible differences in activity between limited and diffuse disease. METHODS:
      Cross-sectional study of a national cohort of patients enrolled in the Canadian
      Scleroderma Research Group Registry. Disease activity was measured using the
      SDAI. Depression scores were measured using the Centre for Epidemiologic Studies
      Depression Scale (CES-D). RESULTS: A total of 326 out of 639 patients had
      complete datasets at the time of this analysis; 87% were female, of mean age 55.6
      years, with mean disease duration 14.1 years. SDAI declined steeply in the first
      5 years after disease onset and patients with diffuse disease had 42% higher SDAI
      scores than patients with limited disease with the same disease duration and
      depression scores (standardized relative risk 1.42, 95% CI 1.21, 1.65). Patients
      with higher CES-D scores had higher SDAI scores relative to patients with the
      same disease duration and disease subset (standardized RR 1.22, 95% CI 1.14,
      1.31). Among the 10 components that make up the SDAI, only skin score
      (standardized OR 0.59, 95% CI 0.43, 0.82) and patient-reported change in skin
      (standardized OR 0.64, 95% CI 0.45, 0.92) decreased with increasing disease
      duration. High skin scores (standardized OR 32.2, 95% CI 15.8, 72.0) were more
      likely and scleredema (standardized OR 0.58, 95% CI 0.37, 0.92) was less likely
      to be present in patients with diffuse disease. High depression scores were
      associated with positive responses for patient-reported changes in skin and
      cardiopulmonary function. CONCLUSION: Disease activity declined with time and
      patients with diffuse disease had consistently higher SDAI scores. Depression was
      found to be associated with higher patient activity scores and strongly
      associated with patient self-response questions. The role of depression should be
      carefully considered in future applications of the SDAI, particularly as several
      components of the score rely upon patient recall.

PMID- 20810507
TI  - Influence of IL2RA rs2104286 polymorphism in the risk of biopsy-proven giant cell
      arteritis.
AB  - OBJECTIVE: To assess the influence of the IL2RA rs2104286 A>G polymorphism on
      susceptibility to and clinical spectrum of manifestations of biopsy-proven giant
      cell arteritis (GCA). METHODS: Our study included 318 patients with biopsy-proven
      GCA. DNA from patients and healthy controls was obtained from peripheral blood.
      Samples were genotyped for the IL2RA rs2104286 A>G polymorphism using a
      predesigned TaqMan allele discrimination assay and by PCR amplification. RESULTS:
      Although GCA patients showed a higher frequency of the minor allele homozygote of
      IL2RA rs2104286 (GG) compared to controls (5.1% vs 2.8%, respectively; p = 0.06,
      odds ratio 1.84, 95% confidence interval 0.91-3.70), the allele distribution
      showed no significant differences between GCA patients and controls.
      Stratification of GCA patients according to sex or polymyalgia rheumatica, jaw
      claudication, visual ischemic manifestations, or other severe ischemic
      complications did not yield significant differences in the allele or genotype
      frequencies of the IL2RA rs2104286 polymorphism. CONCLUSION: IL2RA rs2104286
      polymorphism does not appear to be a genetic risk factor for susceptibility to
      biopsy-proven GCA. Also, this polymorphism does not seem to be implicated in the
      clinical expression of this vasculitis.

PMID- 20810508
TI  - pANCA, ASCA, and OmpC antibodies in patients with ankylosing spondylitis without
      inflammatory bowel disease.
AB  - OBJECTIVE: Patients with ankylosing spondylitis (AS) can suffer concurrently from
      inflammatory bowel disease (IBD), as ulcerative colitis (UC) or Crohn's disease
      (CD). Serological markers have been described to diagnose IBD. We investigated
      IBD serological markers in AS patients without IBD and whether these antibodies
      enable differentiating patients with AS and IBD from those without IBD. METHODS:
      Frequencies of perinuclear antineutrophil cytoplasmic antibodies (pANCA),
      antibodies to the cell-wall mannan of Saccharomyces cerevisiae (ASCA), and
      antibodies to porin protein C of Escherichia coli (OmpC) were evaluated in 179
      patients: 52 with AS, 50 with UC, 51 with CD, and 26 with IBD and AS. Patient
      groups were matched for age and sex. All AS patients fulfilled the 1984 modified
      New York criteria. IBD was ascertained by clinical, endoscopic, and microscopic
      findings. RESULTS: In 55% of the AS patients without manifest IBD at least one
      antibody associated with IBD was observed. pANCA, ASCA (IgA and/or IgG), and OmpC
      antibodies were found in 21%, 30%, and 19% of the AS patients, respectively.
      pANCA was more frequently present in AS with concurrent UC than in AS alone (OR
      8.2, 95% CI 1.2-55.6), thus being an indicator for UC in AS patients. CONCLUSION:
      Antibodies associated with IBD are detectable in more than half of AS patients
      without symptoms or signs of IBD. A relatively recent marker in this setting,
      OmpC antibodies, does not contribute to the differentiation between AS and type
      of IBD. Presence of pANCA, however, is significantly increased in AS patients who
      also have UC, and is an indicator to perform endoscopy. These results corroborate
      a pathophysiological link between AS and IBD.

PMID- 20810509
TI  - Intraarticular botulinum toxin A for refractory painful total knee arthroplasty:
      a randomized controlled trial.
AB  - OBJECTIVE: To assess short-term efficacy of single intraarticular botulinum toxin
      (IA-BoNT/A) injection in patients with chronically painful total knee
      arthroplasty (TKA) in a randomized, placebo-controlled, triple-blind study.
      METHODS: Patients with chronic TKA pain (pain > 6 on 0-10 scale and > 6 months
      post-TKA) evaluated in and referred from orthopedic surgery clinics were
      recruited. The primary outcome, proportion of patients with clinically meaningful
      decrease of at least 2 points on 0-10 visual analog scale (VAS) for pain, was
      compared between treatment groups at 2 months using comparison of proportions
      test and for all efficacy timepoints (2, 3, and 4 months) using generalized
      estimating equations (GEE). Secondary outcomes of global assessment, function,
      and quality of life were compared using GEE, duration of pain relief by t-test,
      and adverse events by chi-square test. RESULTS: In total, 54 patients with 60
      painful TKA were randomized, with main analyses restricted to one TKA per patient
      (49 TKA in 49 patients). Mean age was 67 years, 84% were men, and mean duration
      of TKA pain was 4.5 years. A significantly greater proportion of patients (71%)
      in the IA-BoNT/A group compared to IA-placebo (35%) achieved clinically
      meaningful reduction in VAS pain at 2 months (p = 0.028) and at all efficacy
      timepoints (p = 0.019). Duration of meaningful pain relief was significantly
      greater after IA-BoNT/A, 39.6 days (SD 50.4) compared to IA-placebo, 15.7 days
      (SD 22.6; p = 0.045). Statistically significantly better scores were seen in IA
      BoNT/A vs IA-placebo for all efficacy timepoints for the following outcomes:
      "very much improved" on physician global assessment of change (p = 0.003);
      Western Ontario McMaster Osteoarthritis Index physical function (p = 0.026),
      stiffness (p = 0.004), and total scores (p = 0.024); and Short-Form 36 pain
      subscale score (p = 0.049). Number of total and serious adverse events was
      similar between groups, with no patients in either group with new objective motor
      or sensory deficits during followup. CONCLUSION: In this single-center randomized
      trial, single IA-BoNT/A injection provided clinically meaningful short-term
      improvements in pain, global assessment, and function in patients with chronic
      painful TKA. A multicenter trial is needed to confirm these findings.

PMID- 20810510
TI  - Elevated serum glucose-6-phosphate isomerase correlates with histological disease
      activity and clinical improvement after initiation of therapy in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To determine serum glucose-6-phosphate isomerase (GPI) concentrations
      in patients with rheumatoid arthritis (RA), and to test whether they correlate
      with objective measures of disease activity. METHODS: Sera from 116 patients with
      RA, 69 patients with non-RA rheumatic diseases, and 101 healthy controls were
      analyzed. Levels of soluble serum GPI were measured by ELISA. Histological
      disease activity was determined with the synovitis score in synovial needle
      biopsies from 58 of the 116 patients with RA. Thirty-one of the 58 synovium
      samples were stained for CD68, CD3, CD20, CD38, CD79a, and CD34 by
      immunohistochemistry. Demographic data were collected, as well as serological and
      clinical variables that indicate RA disease activity, for Spearman correlation
      analysis. RESULTS: Serum GPI level correlated positively with the synovitis score
      (r = 0.278, p = 0.034). Significantly higher soluble GPI levels were detected in
      the RA sera compared with sera from healthy controls and the non-RA disease
      controls (2.25 +/- 2.82 vs 0.03 +/- 0.05 and 0.19 +/- 0.57 MUg/ml, respectively;
      p < 0.0001). The rate of serum GPI positivity was significantly higher in the RA
      patients than in the non-RA disease controls (64.7% vs 10.1%; p < 0.0001).
      Spearman analysis showed no significant correlation between serum GPI level and
      Disease Activity Score in 28 joints at baseline. After initiation of
      antirheumatic treatments, GPI levels decreased significantly (2.81 +/- 3.12 vs
      1.44 +/- 2.09 MUg/ml; p = 0.016), paralleling improvement of the disease activity
      indices. CONCLUSION: Elevated serum GPI may be involved in the synovitis of RA
      and may prove useful as a serum marker for disease activity of RA.

PMID- 20810511
TI  - Ultrasonographic measurements of joint cartilage thickness in healthy children:
      age- and sex-related standard reference values.
AB  - OBJECTIVE: Loss of joint cartilage may be an early feature of chronic
      inflammatory joint diseases like juvenile idiopathic arthritis (JIA).
      Conventional radiography usually detects only late changes such as joint space
      narrowing and bone erosion rather than early inflammatory changes. Joint
      cartilage is easily visualized with high-frequency ultrasonography (US), but age-
      and gender-related normal standard reference values should be established before
      US measurement of cartilage thickness becomes standard procedure in the clinic.
      METHODS: A cross-sectional study of bilateral grey-scale US cartilage thickness
      of the knee, ankle, wrist, and second metacarpophalangeal (MCP) and second
      proximal interphalangeal (PIP) joints was performed in 394 (215 boys/179 girls)
      healthy Danish Caucasian children aged between 7 and 16 years. RESULTS: Cartilage
      thickness differed significantly between sexes (p < 0.001 for all joints), boys
      having thicker cartilage than girls. Cartilage thickness clearly decreased with
      increasing age in both sexes. A formula for calculating sex-specific cartilage
      thickness at different ages in childhood is suggested. No difference between the
      right and left side of the investigated joints was observed. CONCLUSION: Using
      US, we established age- and sex-related normal reference intervals for cartilage
      thickness of the knee, ankle, wrist, and MCP and PIP joints in 7- to 16-year-old
      children, and designed a formula for calculating hyaline cartilage thickness in
      all age groups throughout childhood.

PMID- 20810512
TI  - Bosentan improves skin perfusion of hands in patients with systemic sclerosis
      with pulmonary arterial hypertension.
AB  - OBJECTIVE: Our aim was to investigate effects of bosentan on hand perfusion in
      patients with systemic sclerosis (SSc) with pulmonary arterial hypertension
      (PAH), using laser Doppler perfusion imaging (LDPI). METHODS: We enrolled 30 SSc
      patients with PAH, 30 SSc patients without PAH, and 30 healthy controls. In SSc
      patients and healthy controls at baseline, skin blood flow of the dorsum of the
      hands was determined with a Lisca laser Doppler perfusion imager. The dorsal
      surface of the hands was divided into 3 regions of interest (ROI). ROI 1 included
      3 fingers of the hand from the second to the fourth distally to the proximal
      interphalangeal finger joint. ROI 2 included the area between the proximal
      interphalangeal and the metacarpophalangeal joint. ROI 3 included only the dorsal
      surface of the hand without the fingers. LDPI was repeated in SSc patients and
      controls after 4, 8, and 16 weeks of treatment. In SSc patients, nailfold
      videocapillaroscopy and Raynaud Condition Score (RCS) were performed at baseline
      and at 4, 8, and 16 weeks. RESULTS: SSc patients with PAH enrolled in the study
      received treatment with bosentan as standard care for PAH. In these patients with
      PAH, after 8 and 16 weeks of treatment, bosentan improved minimum, mean, and
      maximum perfusion and the perfusion proximal-distal gradient. Bosentan seems to
      be most effective in patients with the early and active capillaroscopic pattern
      than in patients with the late pattern. Bosentan improved skin blood flow
      principally in the ROI 1 compared to the ROI 2 and ROI 3. Bosentan restored the
      perfusion proximal-distal gradient in 57% of SSc patients with the early
      capillaroscopic pattern. No significant differences from baseline were observed
      in the RCS in SSc patients with PAH. CONCLUSION: Bosentan improved skin perfusion
      in SSc patients with PAH, although it did not ameliorate symptoms of Raynaud's
      phenomenon. Skin blood perfusion increased in SSc patients with PAH, particularly
      in the skin region distal to the proximal interphalangeal joint, and in patients
      with the early/active capillaroscopic pattern. Double-blind randomized clinical
      trials are needed to evaluate the effects of bosentan on skin perfusion of SSc
      patients without PAH and with active digital ulcers.

PMID- 20810513
TI  - Evaluation of selected rheumatoid arthritis activity scores for office-based
      assessment.
AB  - OBJECTIVE: Patient-reported measures can quickly provide assessments of
      rheumatoid arthritis (RA) disease activity in the office setting and do not
      require a laboratory test or physician examination. The goal of our study was to
      establish the validity of patient-reported indices compared to the C-reactive
      protein-based Disease Activity Score (DAS28-CRP4). METHODS: Baseline and 1-year
      followup DAS28-CRP4 data were obtained from 740 RA subjects and were compared to
      indices (MDHAQ, CDAI, RAPID, RADAI, GAS) according to cyclic citrullinated
      peptide (CCP) status and change at 1 year. Pairwise correlations were calculated
      for each index. RESULTS: Among 740 subjects, mean age 57 years, disease duration
      14 years, the CDAI (r = 0.84, Delta r = 0.80) and RAPID (r = 0.71, Delta r =
      0.70) had the highest correlation with the DAS28-CRP4 scores at baseline and 1
      year. These correlations were not influenced by CCP status, disease-modifying
      antirheumatic drug use, biologic use, or by disease duration. CONCLUSION: In RA,
      the CDAI and RAPID correlated well with the DAS28-CRP4. They may both be
      practical and informative in the care of patients in the office setting.

PMID- 20810514
TI  - Increased production of a proliferation-inducing ligand (APRIL) by peripheral
      blood mononuclear cells is associated with antitopoisomerase I antibody and more
      severe disease in systemic sclerosis.
AB  - OBJECTIVE: A proliferation-inducing ligand (APRIL), a member of the tumor
      necrosis factor (TNF) family, plays a crucial role in the survival of peripheral
      B cells, and may contribute to the pathogenesis of systemic sclerosis (SSc)
      through upregulation of autoantibody production and maintenance of autoimmune
      phenomena. We evaluated the capacity of peripheral blood mononuclear cells from
      patients with SSc (SSc-PBMC) to produce APRIL; and investigated correlations
      between production of APRIL by SSc-PBMC and clinical and laboratory features of
      the disease. METHODS: PBMC from 20 patients with SSc and 14 healthy subjects were
      incubated in fetal calf serum-supplemented RPMI medium. APRIL levels were
      determined in cell culture supernatants by ELISA. RESULTS: PBMC from patients
      with SSc produced significantly more APRIL (961 +/- 151 pg/ml/105 cells) than
      control PBMC (798 +/- 219 pg/ml/105 cells; p < 0.01). In patients with SSc,
      increased production of APRIL was associated with the presence of diffuse skin
      involvement, scleroderma lung disease, peripheral vasculopathy, greater capillary
      damage on capillaroscopy, and presence of anti-topoisomerase I (anti-topo I)
      antibodies. Multivariate regression analysis revealed anti-topo I antibodies as
      the only independent predictor of high production of APRIL by PBMC. CONCLUSION:
      Production of APRIL is increased in SSc-PBMC and is associated with the presence
      of anti-topo I antibodies and more severe disease. Targeting the APRIL pathway
      might represent a therapeutic possibility for treatment of patients with SSc, in
      particular those with anti-topo I antibodies.

PMID- 20810515
TI  - Early predictors of juvenile sacroiliitis in enthesitis-related arthritis.
AB  - OBJECTIVE: To identify early predictors of sacroiliac (SI) involvement in a
      cohort of patients with enthesitis-related arthritis (ERA). METHODS: During a 7
      year followup period, all consecutive patients fulfilling the ILAR classification
      criteria for ERA were enrolled. Data collected included demographic, clinical and
      laboratory variables at disease onset, at the onset of inflammatory back pain,
      and at the last available followup visit. Pelvis radiographs and dynamic magnetic
      resonance imaging (MRI) scans for SI joints were obtained simultaneously in all
      patients who developed inflammatory back pain. RESULTS: Fifty-nine children with
      ERA were studied; 40 male, 19 female; median age at disease onset 9 years 4
      months (range 6 yrs 6 mo - 13 yrs 3 mo). At a median interval after disease onset
      of 1 year 3 months, 21 children reported symptoms of inflammatory back pain. In
      all cases, radiographs of SI joints were negative, while dynamic MRI revealed
      acute sacroiliitis in 17 cases. Multivariate analysis showed that the early
      predictors of SI were the number of active joints (p < 0.03) and the number of
      active entheses (p < 0.001) at onset. CONCLUSION: In our cohort, roughly 30% of
      children with ERA/juvenile idiopathic arthritis develop clinical and MRI evidence
      of sacroiliitis, detectable with dynamic MRI as early as 1 year after disease
      onset. Additional data from larger case series are needed to assess the
      specificity and sensitivity of this technique in the early phase of the disease
      and to confirm the rate of SI involvement reported in this cohort.

PMID- 20810516
TI  - Comparative study of mitoxantrone efficacy profile in patients with relapsing
      remitting and secondary progressive multiple sclerosis.
AB  - BACKGROUND: Mitoxantrone (MTX) is an immunosuppressive drug approved for multiple
      sclerosis (MS) treatment. OBJECTIVE: The aim of this study is to evaluate and to
      compare the clinical and neuroradiological responses to MTX in relapsing
      remitting (RR) and secondary progressive (SP) MS patients. METHODS: We conducted
      a retrospective, non-randomized, open-label, observational study to evaluate the
      clinical and neuroradiological response to the drug in 79 patients with RR MS and
      210 patients with SP MS. RESULTS: A statistically significant reduction (p <
      0.001) in the number of relapses was observed during MTX treatment and in the
      year after in both RR and SP MS patients. On the contrary, an opposite behavior
      in terms of disease progression was found in RR compared with SP MS patients,
      resulting in a statistically significant improvement of the Expanded Disability
      Status Scale score during the MTX treatment (p < 0.001) and in the year after (p
      < 0.001) for RR MS patients compared with a continuous, although mild, worsening
      of the disability in SP MS patients (p < 0.001). Finally, a significant reduction
      (p < 0.001) of new Gd-enhanced lesions in both RR and SP MS patients was observed
      in a subgroup of 224 individuals who underwent a brain MRI evaluation before and
      after MTX treatment. CONCLUSIONS: MTX should be considered as an effective
      therapeutic option in RR MS patients with evidence of relevant disease activity,
      but the potential life-threatening adverse events and the overall benefit-risk
      ratio must be carefully evaluated at individual patient level.

PMID- 20810517
TI  - Assessing changes in relapse rates in multiple sclerosis.
AB  - Multiple Sclerosis (MS) annualized relapse rates (ARRs) in trials may be
      declining due to changes in diagnostic criteria, MS etiology, study criteria, and
      selection biases. This review examines if there is a trend in the ARR for
      relapsing-remitting MS patients (RRMS) over time and if so, why. A comprehensive
      literature search was performed using PubMed, Web of Science((r)), and the
      Cochrane Library using electronic searches, screen scraping for abstracts, and
      hand searching of references for randomized trials conducted between 1960 and
      2008. Out of 72 randomized trials, 56 (77.8%) defined relapse. This study uses 32
      placebo relapsing-remitting studies out of the 37 (66.1%) with RRMS. The mean ARR
      for the treatment arms was 0.68 and the one for the placebo groups was 1.002. The
      year of publication was negatively associated with the ARR (p = 0.0001). The
      annual reduction amounts to 0.36 relapses over a 10-year period. Age and duration
      of symptoms were negatively associated with the ARR. Year of publication was
      significantly negatively associated with ARR after controlling for covariates.
      ARRs have fallen with relapse definition, entrance criteria remain important, but
      time exceeds all these variables and reflects two likely sources, selection of
      patients for trials by clinicians and rescue of patients truncating the number of
      multiple relapses. The impact of truncating the number of relapses on the falling
      rates is important, not only on the ARRs, but also on the impact of informative
      censoring in drop-outs.

PMID- 20810518
TI  - What matters: the lived experience with musculoskeletal health conditions.

PMID- 20810519
TI  - Work-associated arthritis productivity loss: where do we stand in its
      measurement?

PMID- 20810520
TI  - Is the whole greater than the sum of its parts?

PMID- 20810521
TI  - Is DISH painful?

PMID- 20810522
TI  - Erdheim-Chester disease.

PMID- 20810523
TI  - Significance of "Erosion-like Lesions" in "Healthy Controls".

PMID- 20810524
TI  - Caveat on the interpretation of metacarpal head erosions seen by magnetic
      resonance imaging.

PMID- 20810525
TI  - Anticyclic citrullinated peptide antibodies as markers of erosive arthritis in
      antisynthetase syndrome.

PMID- 20810526
TI  - Testing for hypoxia in forearm skin of patients with systemic sclerosis, assessed
      by pimonidazole.

PMID- 20810527
TI  - Discontinuation of etanercept after successful treatment in patients with
      juvenile idiopathic arthritis.

PMID- 20810528
TI  - Effectiveness of colchicine therapy in 4 cases of retroperitoneal fibrosis
      associated with autoinflammatory diseases.

PMID- 20810529
TI  - The dilemma of central serous retinopathy, a corticosteroid-induced complication,
      in patients with ocular inflammatory disease.

PMID- 20810530
TI  - Successful desensitization for hydroxychloroquine anaphylaxis.

PMID- 20810531
TI  - A rare cause of foot swelling mimicking tenosynovitis.

PMID- 20810532
TI  - Mnemonic for assessment of the spondyloarthritis international society criteria.

PMID- 20810533
TI  - Interference of remote magnetic catheter navigation and ablation with implanted
      devices for pacing and defibrillation.
AB  - AIMS: Remote magnetic catheter navigation (RMN) may facilitate catheter ablation.
      However, as the system uses permanent magnets, interference (INF) with devices
      for pacing [pacemaker (PM)], defibrillation [implantable cardioverter
      defibrillators (ICD)], or cardiac resynchronisation [cardiac resynchronization
      therapy (CRT)] may occur. We investigated the effects of the RMN system on
      implanted arrhythmia devices in a prospective series. METHODS AND RESULTS: Prior
      to RMN-guided electrophysiological procedures, devices were fully interrogated
      and programmed to VVI 40/min with tachycardia detection off (if applicable).
      Periprocedural device performance was monitored by 12-lead electrocardiogram, and
      duration and effect of asynchronous stimulation resulting from INF were
      evaluated. Following the procedure, devices were again interrogated and system
      integrity verified. A total of 21 procedures in 18 patients with implanted
      devices [PM n = 12, ICD n = 3, CRT-pacemaker (P) n = 1, CRT-defibrillation (D) n
      = 2] were evaluated. No relevant changes in lead parameters or device programming
      were observed after the procedure. No INF was noted in ICD/CRT-D devices
      (tachycardia detection off) and in 2 PMs, whereas 10 PMs and 1 CRT-P switched to
      asynchronous stimulation for 1.8 +/- 0.3 h (63 +/- 13% of RMN duration) without
      clinical adverse effects. In one patient, ventricular tachycardia (VT)
      degenerating in ventricular fibrillation occurred, but no causal relation between
      INF and VT initiation could be ascertained. CONCLUSION: This prospective data
      provide no evidence that using RMN in patients with implanted arrhythmia devices
      may cause persistent device dysfunction. Asynchronous PM stimulation is common
      without negative clinical consequences. Although a causal role of INF for the VT
      observed seems unlikely, risks and benefits of RMN utilization should carefully
      be weighed for each patient with an implanted arrhythmia device.

PMID- 20810534
TI  - Development and validation of a liquid chromatography-mass spectrometry
      metabonomic platform in human plasma of liver failure caused by hepatitis B
      virus.
AB  - This paper presents an liquid chromatography (LC)/mass spectrometry (MS)-based
      metabonomic platform that combined the discovery of differential metabolites
      through principal component analysis (PCA) with the verification by selective
      multiple reaction monitoring (MRM). These methods were applied to analyze plasma
      samples from liver disease patients and healthy donors. LC-MS raw data (about
      1000 compounds), from the plasma of liver failure patients (n = 26) and healthy
      controls (n = 16), were analyzed through the PCA method and a pattern recognition
      profile that had significant difference between liver failure patients and
      healthy controls (P < 0.05) was established. The profile was verified in 165
      clinical subjects. The specificity and sensitivity of this model in predicting
      liver failure were 94.3 and 100.0%, respectively. The differential ions with m/z
      of 414.5, 432.0, 520.5, and 775.0 were verified to be consistent with the results
      from PCA by MRM mode in 40 clinical samples, and were proved not to be caused by
      the medicines taken by patients through rat model experiments. The compound with
      m/z of 520.5 was identified to be 1-Linoleoylglycerophosphocholine or 1
      Linoleoylphosphatidylcholine through exact mass measurements performed using Ion
      Trap-Time-of-Flight MS and METLIN Metabolite Database search. In all, it was the
      first time to integrate metabonomic study and MRM relative quantification of
      differential peaks in a large number of clinical samples. Thereafter, a rat model
      was used to exclude drug effects on the abundance of differential ion peaks. 1
      Linoleoylglycerophosphocholine or 1-Linoleoylphosphatidylcholine, a potential
      biomarker, was identified. The LC/MS-based metabonomic platform could be a
      powerful tool for the metabonomic screening of plasma biomarkers.

PMID- 20810535
TI  - Promotion of markerless deletion of the actinorhodin biosynthetic gene cluster in
      Streptomyces coelicolor.
AB  - The standard gene disruption and replacement to delete the actinorhodin
      biosynthetic gene cluster (Act) in Streptomyces coelicolor was inefficient, and
      the polymerase chain reaction-targeting of the cosmid could efficiently delete
      the Act, but still was a time-consuming procedure for markerless gene
      replacement. By using optimal Streptomyces codons, we synthesized a sceS gene
      encoding identical amino acid sequence as the chromosome rare-cutting
      meganuclease I-sce I of the Saccharomyces cerevisiae mitochondria. Expression of
      sceS gene in S. coelicolor resulted in promotion of homologous recombination and
      subsequently, successful achieved markerless deletion of the Act. The sceS system
      may be useful for the sequential markerless deletions of chromosomal segments in
      Streptomyces.

PMID- 20810536
TI  - Large-scale proteome investigation in wild relatives (A, B, and D genomes) of
      wheat.
AB  - Large-scale proteomics of three wild relatives of wheat grain (A, B, and D
      genomes) were analyzed by using multidimensional protein identification
      technology coupled to liquid chromatography quadruple mass spectrometry. A total
      of 1568 (peptide match >=1) and 255 (peptide match >=2) unique proteins were
      detected and classified, which represents the most wide-ranging proteomic
      exploitation to date. The development of standard proteomes exhibiting all of the
      proteins involved in normal physiology will facilitate the delineation of
      disease/defense, metabolism, energy metabolism, and protein synthesis. A relative
      proteome exploration of the expression patterns indicates that proteins are
      involved in abiotic and biotic stress. Functional category analysis indicates
      that these differentially expressed proteins are mainly involved in
      disease/defense (15.38%, 21.26%, and 16.78%), metabolism (8.39%, 12.07%, and
      14.09%), energy metabolism (11.19%, 11.49%, and 13.42%), protein synthesis
      (9.09%, 9.20%, and 8.72%), cell growth and division (9.09%, 4.60%, and 6.04%),
      cellular organization (4.20%, 5.75%, and 5.37%), development (6.29%, 2.87%,
      3.36%), folding and stability (6.29%, 8.62%, and 8.05%), signal transduction
      (11.19%, 7.47%, and 8.05%), storage protein (4.20%, 1.72%, and 2.01%),
      transcription (5.59%, 5.17%, and 4.03%), and transport facilitation (1.40%,
      1.15%, and 3.36%) in A, B, and D genomes, respectively. Here, we reported genome
      specific protein interaction network using Cytoscape software, which provides
      further insight into the molecular functions and mechanism of biochemical
      pathways. We provide a promising understanding about the expressed proteins and
      protein functions. Our approach should be applicable as a marker to assist in
      breeding or gene transfer for quality and stress research of cultivated wheat.

PMID- 20810537
TI  - The ends of a large RNA molecule are necessarily close.
AB  - We show on general theoretical grounds that the two ends of single-stranded (ss)
      RNA molecules (consisting of roughly equal proportions of A, C, G and U) are
      necessarily close together, largely independent of their length and sequence.
      This is demonstrated to be a direct consequence of two generic properties of the
      equilibrium secondary structures, namely that the average proportion of bases in
      pairs is ~60% and that the average duplex length is ~4. Based on mfold and Vienna
      computations on large numbers of ssRNAs of various lengths (1000-10 000 nt) and
      sequences (both random and biological), we find that the 5'-3' distance-defined
      as the sum of H-bond and covalent (ss) links separating the ends of the RNA chain
      is small, averaging 15-20 for each set of viral sequences tested. For random
      sequences this distance is ~12, consistent with the theory. We discuss the
      relevance of these results to evolved sequence complementarity and specific
      protein binding effects that are known to be important for keeping the two ends
      of viral and messenger RNAs in close proximity. Finally we speculate on how our
      conclusions imply indistinguishability in size and shape of equilibrated forms of
      linear and covalently circularized ssRNA molecules.

PMID- 20810538
TI  - Sex differences in UDP-glucuronosyltransferase 2B17 expression and activity.
AB  - UDP-glucuronosyltransferases (UGTs) are enzymes involved in the metabolism of
      steroid hormones, carcinogens, cancer chemotherapy agents, and addictive agents
      from cigarettes. Because the UGT2B family of genes has been linked to hormonal
      regulation in human cell lines in vitro, we hypothesized that there may be sex
      related differences in the expression and activity of these genes in human
      tissues. To evaluate whether there are sex differences in UGT2B expression and
      activity, we examined 103 normal human liver specimens for UGT2B expression by
      real-time polymerase chain reaction and in vitro glucuronidation activities in
      human liver microsomes (HLM). Men exhibited an approximately 4-fold higher level
      of expression of UGT2B17 than women (p = 0.007). Consistent with the increased
      expression of UGT2B17 in men, HLM from men also had a higher level of
      glucuronidation activity than HLM from women against three UGT2B17 substrates: 3
      fold higher for 17-dihydroexemestane (p = 0.002); 3-fold higher for 3
      hydroxycotinine (p < 0.001); and 1.5-fold higher for suberoylanilide hydroxamic
      acid (p = 0.014). When we stratified by UGT2B17 gene deletion genotype, similar
      patterns were observed for all three substrates, with HLM from men with the
      UGT2B17 (+/+) or (+/0) genotypes exhibiting significantly higher levels of
      glucuronidation activity against all three substrates compared with HLM from
      women. These data suggest that men have a higher amount of UGT2B17
      glucuronidation activity then women. This sex difference in UGT2B17 gene
      expression and corresponding protein activity could potentially result in
      different levels of carcinogen detoxification or drug elimination in men versus
      women.

PMID- 20810539
TI  - In vitro evaluation of inhibitory effects of antidiabetic and antihyperlipidemic
      drugs on human carboxylesterase activities.
AB  - Human carboxylesterase (CES) 1A is responsible for the biotransformation of
      angiotensin-converting enzyme (ACE) inhibitors such as imidapril and temocapril.
      Because antidiabetic or antihyperlipidemic drugs are often coadministered with
      ACE inhibitors in clinical pharmacotherapy, the inhibitory effect of these drugs
      on CES1A1 enzyme activity was investigated. In addition, the inhibitory effect on
      CES2 enzyme activity was evaluated to compare it with that on CES1A1. The
      inhibitory effects were evaluated with 11 antidiabetic and 12 antihyperlipidemic
      drugs. The imidapril hydrolase activity by recombinant CES1A1 was substantially
      inhibited by lactone ring-containing statins such as simvastatin and lovastatin
      and thiazolidinediones such as troglitazone and rosiglitazone. The activity in
      human liver microsomes was also strongly inhibited by simvastatin and
      troglitazone (K(i) = 0.8 +/- 0.1 and 5.6 +/- 0.2 MUM, respectively). However,
      statins containing no lactone ring such as pravastatin and fluvastatin did not
      show strong inhibition. 7-Ethyl-10-[4-(1-piperidono)-1
      piperidono]carbonyloxycamptothecin hydrolase activity by recombinant human CES2
      was substantially inhibited by fenofibrate (K(i) = 0.04 +/- 0.01 MUM) as well as
      by simvastatin (0.67 +/- 0.09 MUM). Other fibrates such as clinofibrate and
      bezafibrate did not show strong inhibition. Thus, the inhibitory effects of the
      thiazolidinediones and fenofibrate on CES1A1 and CES2 were different. Some
      statins such as simvastatin and lovastatin, thiazolidinediones, and fenofibrate
      might attenuate the drug efficacy of prodrugs biotransformed by CES1A and CES2.

PMID- 20810540
TI  - Characterization of human flavin-containing monooxygenase (FMO) 3 and FMO5
      expressed as maltose-binding protein fusions.
AB  - The flavin-containing monooxygenase (FMO) family of enzymes oxygenates
      nucleophilic xenobiotics and endogenous substances. Human FMO3 and FMO5 are the
      predominant FMO forms in adult liver. These enzymes are naturally membrane-bound,
      and recombinant proteins are commercially available as microsomal preparations
      from insect cells (i.e., Supersome FMO). As an alternative, FMO3 has previously
      been expressed as a soluble protein, through use of an N-terminal maltose-binding
      protein (MBP) fusion. In the current study, MBP fusions of both human FMO3 and
      FMO5 were prepared to >90% purity in the presence of detergent and characterized
      for biochemical and kinetic parameters, and the parameters were compared with
      those of Supersome FMO samples. Although MBP-FMO enzymes afforded lower rates of
      turnover than the corresponding Supersome FMOs, both types of FMO showed
      identical substrate dependencies and similar responses to changes in assay
      conditions. Of interest, the FMO3 enzymes showed a 2-fold activation of
      k(cat)/K(m) in the presence of Triton X-100. Oligomeric analysis of MBP-FMO3 also
      showed disassociation from a high-order oligomeric form to a monomeric status in
      the presence of Triton X-100. This report serves as the first direct comparison
      between Supersome FMOs and the corresponding MBP fusions and the first report of
      a detergent-based activation of k(cat)/K(m) that corresponds to changes in
      oligomerization.

PMID- 20810542
TI  - Modeling bone marrow toxicity using kinase structural motifs and the inhibition
      profiles of small molecular kinase inhibitors.
AB  - The cellular function of kinases combined with the difficulty of designing
      selective small molecule kinase inhibitors (SMKIs) poses a challenge for drug
      development. The late-stage attrition of SMKIs could be lessened by integrating
      safety information of kinases into the lead optimization stage of drug
      development. Herein, a mathematical model to predict bone marrow toxicity (BMT)
      is presented which enables the rational design of SMKIs away from this safety
      liability. A specific example highlights how this model identifies critical
      structural modifications to avoid BMT. The model was built using a novel
      algorithm, which selects 19 representative kinases from a panel of 277 based upon
      their ATP-binding pocket sequences and ability to predict BMT in vivo for 48
      SMKIs. A support vector machine classifier was trained on the selected kinases
      and accurately predicts BMT with 74% accuracy. The model provides an efficient
      method for understanding SMKI-induced in vivo BMT earlier in drug discovery.

PMID- 20810541
TI  - The role of CaMKII in calcium-activated death pathways in bone marrow B cells.
AB  - Calcium is an essential signaling molecule in developing B cells, thus altering
      calcium dynamics represents a potential target for toxicant effects. GW7845, a
      tyrosine analog and potent peroxisome proliferator-activated receptor gamma
      agonist, induces rapid mitogen-activated protein kinase (MAPK)-dependent
      apoptosis in bone marrow B cells. Changes in calcium dynamics are capable of
      mediating rapid initiation of cell death; therefore, we investigated the
      contribution of calcium to GW7845-induced apoptosis. Treatment of a
      nontransformed murine pro/pre-B cell line (BU-11) with GW7845 (40 MUM) resulted
      in intracellular calcium release. Multiple features of GW7845-induced cell death
      were suppressed by the calcium chelator BAPTA, including MAPK activation, loss of
      mitochondrial membrane potential, cytochrome c release, caspase-3 activation, and
      DNA fragmentation. A likely mechanism for the calcium-mediated effects is
      activation of CaMKII, a calcium-dependent MAP4K. We observed that three CaMKII
      isoforms (beta, gamma, and delta) are expressed in lymphoid tissues and bone
      marrow B cells. Treatment with GW7845 increased CaMKII activity. All features of
      GW7845-induced cell death, except loss of mitochondrial membrane potential, were
      suppressed by CaMKII inhibitors (KN93 and AIP-II), suggesting the activation of
      multiple calcium-driven pathways. To determine if CaMKII activation is a common
      feature of early B cell death following perturbation of Ca(2+) flux, we dissected
      tributyltin (TBT)-induced death signaling. High-dose TBT (1 MUM) is known to
      activate calcium-dependent death. TBT induced rapid apoptosis that was associated
      with intracellular calcium release, CaMKII activation and MAPK activation, and
      was inhibited by AIP-II. Thus, we show that early B cells are susceptible to
      calcium-triggered cell death through a CaMKII/MAPK-dependent pathway.

PMID- 20810543
TI  - Sulforaphane inhibits 4-aminobiphenyl-induced DNA damage in bladder cells and
      tissues.
AB  - Sulforaphane (SF) is a well-known chemopreventive phytochemical and occurs in
      broccoli and to a lesser extent in other cruciferous vegetables, whereas 4
      aminobiphenyl (ABP) is a major human bladder carcinogen and is present at
      significant levels in tobacco smoke. Here, we show that SF inhibits ABP-induced
      DNA damage in both human bladder cells in vitro and mouse bladder tissue in vivo,
      using dG-C8-ABP as a biomarker, which is the predominant ABP-DNA adduct formed in
      human bladder cells and tissues. SF activates NF-E2 related factor-2 (Nrf2),
      which is a well-recognized chemopreventive target and activates the Nrf2
      regulated cytoprotective signaling pathway. Comparison between wild-type mice and
      mice without Nrf2 shows that Nrf2 activation is required by SF for inhibition of
      ABP-induced DNA damage. Moreover, Nrf2 activation by SF in the bladder occurs
      primarily in the epithelium, which is the principal site of bladder cancer
      development. These data, together with our recent observation that SF-enriched
      broccoli sprout extracts strongly inhibits N-butyl-N-(4-hydroxybutyl)nitrosamine
      induced bladder cancer development, suggest that SF is a highly promising agent
      for bladder cancer prevention and provides a mechanistic insight into the
      repeated epidemiological observation that consumption of broccoli is inversely
      associated with bladder cancer risk and mortality.

PMID- 20810544
TI  - Association between hsa-mir-146a genotype and tumor age-of-onset in BRCA1/BRCA2
      negative familial breast and ovarian cancer patients.
AB  - An increasing body of evidence points to a possible role of microRNAs (miRNAs) in
      hereditary cancer syndromes. To evaluate the role of miRNA allelic variants in
      the susceptibility to familial breast and ovarian cancers in BRCA1/BRCA2-negative
      patients, we focused our attention on three miRNAs, miR-146a, miR-17 and miR-369,
      based on their affinity to either BRCA1 or BRCA2 messenger RNA and their
      localization on chromosome regions commonly deleted in those tumors. The analysis
      was performed on 101 Italian probands with ascertained familiarity for
      breast/ovarian cancer and tested negative for both BRCA1 and BRCA2 gene
      mutations. No allelic variant was detected for hsa-mir-17 and hsa-mir-369, and
      allelic and genotype frequencies for miR-146a rs2910164 single-nucleotide
      polymorphism (SNP) were comparable with that of 155 controls from the same
      population, ruling out a role for genetic variations in these three miRNAs as
      major determinants in cancer predisposition of BRCA1/BRCA2-negative patients.
      Instead, our study suggests that mir-146a rs2910164 SNP may impact on the age of
      cancer onset. In fact, subjects with mir-146a a GC or CC genotypes developed
      tumors at younger age compared with individuals with the GG genotype Thus, in
      contrast to a recent report, our data support the hypothesis by Shen and
      coworkers of an association between the C allele of hsa-mir-146a and early cancer
      onset and prompt further investigations on the relevance of this polymorphism in
      early familial breast/ovarian tumor development.

PMID- 20810545
TI  - Arabidopsis histone methyltransferase SET DOMAIN GROUP8 mediates induction of the
      jasmonate/ethylene pathway genes in plant defense response to necrotrophic fungi.
AB  - As sessile organisms, plants have to endure a wide variety of biotic and abiotic
      stresses, and accordingly they have evolved intricate and rapidly inducible
      defense strategies associated with the activation of a battery of genes. Among
      other mechanisms, changes in chromatin structure are thought to provide a
      flexible, global, and stable means for the regulation of gene transcription. In
      support of this idea, we demonstrate here that the Arabidopsis (Arabidopsis
      thaliana) histone methyltransferase SET DOMAIN GROUP8 (SDG8) plays a crucial role
      in plant defense against fungal pathogens by regulating a subset of genes within
      the jasmonic acid (JA) and/or ethylene signaling pathway. We show that the loss
      of-function mutant sdg8-1 displays reduced resistance to the necrotrophic fungal
      pathogens Alternaria brassicicola and Botrytis cinerea. While levels of JA, a
      primary phytohormone involved in plant defense, and camalexin, a major
      phytoalexin against fungal pathogens, remain unchanged or even above normal in
      sdg8-1, induction of several defense genes within the JA/ethylene signaling
      pathway is severely compromised in response to fungal infection or JA treatment
      in mutant plants. Both downstream genes and, remarkably, also upstream mitogen
      activated protein kinase kinase genes MKK3 and MKK5 are misregulated in sdg8-1.
      Accordingly, chromatin immunoprecipitation analysis shows that sdg8-1 impairs
      dynamic changes of histone H3 lysine 36 methylation at defense marker genes as
      well as at MKK3 and MKK5, which normally occurs upon infection with fungal
      pathogens or methyl JA treatment in wild-type plants. Our data indicate that SDG8
      mediated histone H3 lysine 36 methylation may serve as a memory of permissive
      transcription for a subset of defense genes, allowing rapid establishment of
      transcriptional induction.

PMID- 20810546
TI  - Clinical activity of bortezomib in relapsed/refractory MALT lymphomas: results of
      a phase II study of the International Extranodal Lymphoma Study Group (IELSG).
AB  - BACKGROUND: The nuclear factor-kappa B activation in mucosa-associated lymphoid
      tissue (MALT) lymphoma pathogenesis provided the rationale for the evaluation of
      bortezomib in this malignancy. PATIENTS AND METHODS: Thirty-two patients with
      relapsed/refractory MALT lymphoma were enrolled. Thirty-one patients received
      bortezomib 1.3 mg/m(2) i.v., on days 1, 4, 8, and 11, for up to six 21-day
      cycles. RESULTS: Median age was 63 years (range, 37-82 years). Median number of
      prior therapies was 2 (range, 1-4). Nine patients had Ann Arbor stage I, 7
      patients had stage II, and 16 patients had stage IV. Primary lymphoma
      localization was the stomach in 14 patients; multiple extranodal sites were
      present in 10 patients. Among the 29 patients assessable for response, the
      overall response rate was 48% [95% confidence interval (CI) 29% to 67%], with 9
      complete and 5 partial responses. Nine patients experienced stable disease and
      six had disease progression during therapy. The most relevant adverse events were
      fatigue, thrombocytopenia, neutropenia, and peripheral neuropathy. After a median
      follow-up of 24 months, the median duration of response was not reached yet. Five
      deaths were reported, in two patients due to disease progression. CONCLUSION:
      Bortezomib is active in relapsed MALT lymphomas. Further investigations to
      identify optimal bortezomib dose, schedule, and combination regimens are needed
      since the frequent detection of dose-limiting peripheral neuropathy.

PMID- 20810547
TI  - Cisplatin-based chemoradiation plus cetuximab in locally advanced head and neck
      cancer: a phase II clinical study.
AB  - BACKGROUND: Intensification of chemoradiation for advanced head and neck squamous
      cell carcinoma (HNSCC) is unlikely due to toxicity. Cetuximab combined either
      with radiotherapy or with chemotherapy showed favourable toxic profile with
      positive results in both combinations. Therefore, cetuximab could intensify
      chemoradiation without worsening toxicity. We conducted a phase II study of
      chemoradiation and cetuximab. PATIENTS AND METHODS: Eligible patients had stage
      III-IV M0 HNSCC. Treatment consisted of three cycles of cisplatin (20 mg/m(2)/day
      * 5 days) and fluorouracil (200 mg/m(2)/day * 5 days) rapidly alternated to three
      split courses of radiotherapy up to 70 Gy and concurrent weekly cetuximab. The
      primary end point of the study was complete response (CR) rate. Secondary end
      points were toxicity, progression-free survival (PFS) and overall survival (OS).
      RESULTS: Fourty-five patients were enrolled: median age was 56 years, 38 had
      stage IV disease and 40 nodal involvement. CR occurred in 32 patients (71%). PFS
      and OS was 21+ months and 32.6+, respectively. Acute grade 3-4 toxic effects were
      in the expected range, but grade 3 radiodermatitis occurred in 33 patients.
      CONCLUSIONS: The combination of cetuximab, cisplatin, fluorouracil and
      radiotherapy leads to a very high proportion of CR and it is feasible with toxic
      effects similar to those expected by radiochemotherapy. The only unexpected
      toxicity was skin toxicity: grade 3 radiodermatitis occurred in 73% of the
      patients.

PMID- 20810548
TI  - Ancestral roles of small RNAs: an Ago-centric perspective.
AB  - RNAi has existed at least since the divergence of prokaryotes and eukaryotes.
      This collection of pathways responds to a diversity of "abberant" RNAs and
      generally silences or eliminates genes sharing sequence content with the
      silencing trigger. In the canonical pathway, double-stranded RNAs are processed
      into small RNAs, which guide effector complexes to their targets by complementary
      base pairing. Many alternative routes from silencing trigger to small RNA are
      continuously being uncovered. Though the triggers of the pathway and the
      mechanisms of small RNA production are many, all RNAi-related mechanisms share
      Argonaute proteins as the heart of their effector complexes. These can act as
      self-contained silencing machines, binding directly to small RNAs, carrying out
      homology-based target recognition, and in some cases cleaving targets using an
      endogenous nuclease domain. Here, we discuss the diversity of Argonaute proteins
      from a structural and functional perspective.

PMID- 20810550
TI  - Evaluation of the clinical efficacy of pradofloxacin tablets for the treatment of
      canine pyoderma.
AB  - A third-generation fluoroquinolone, pradofloxacin (PRA), is currently being
      developed to treat bacterial infections in dogs. The purpose of this study was to
      assess the clinical efficacy in 20 dogs affected with superficial and deep
      pyoderma. An initial aerobic skin culture was performed in dogs with superficial
      pyoderma; aerobic/anaerobic tissue culture was performed in dogs with deep
      pyoderma; and skin cytology and biopsies were obtained from all dogs.
      Pradofloxacin (approximately 3 mg/kg per os [PO]) was administered daily to all
      dogs. Clinical efficacy was recorded at 4 weeks for dogs with superficial
      pyoderma and at 3 and 6 weeks for dogs with deep pyoderma. At a mean dosage of
      3.7 mg/kg PO once daily, PRA treatment resulted in an excellent to good clinical
      response within 3 to 6 weeks for all 20 dogs with superficial and deep pyoderma.

PMID- 20810551
TI  - Chylothorax treated via thoracic duct ligation and omentalization.
AB  - Chylothorax is an uncommon, potentially life-threatening disease of dogs and
      cats. Medical records of 12 animals (five dogs and seven cats) undergoing
      surgical management of chylothorax from 2001 to 2005 were reviewed. All animals
      received thoracic duct ligation and thoracic omentalization. In some cases, a
      combination of subtotal pericardectomy and/or pleural stripping was also
      employed. All animals survived surgery, and none was lost to follow-up. Median
      survival time for cats was 209 days (range 2 to 1328 days), and for dogs it was
      211 days (range 7 to 991 days). Although postoperative mortality was higher than
      in other recent studies, no complications could be directly attributed to
      thoracic omentalization. A controlled, prospective study is needed to compare
      outcomes of this management method to those of other methods.

PMID- 20810549
TI  - TGF-beta biology in mammary development and breast cancer.
AB  - Transforming growth factor-beta1 (TGF-beta) was first implicated in mammary
      epithelial development by Daniel and Silberstein in 1987 and in breast cancer
      cells and hormone resistance by Lippman and colleagues in 1988. TGF-beta is
      critically important for mammary morphogenesis and secretory function through
      specific regulation of epithelial proliferation, apoptosis, and extracellular
      matrix. Differential TGF-beta effects on distinct cell types are compounded by
      regulation at multiple levels and the influence of context on cellular responses.
      Studies using controlled expression and conditional-deletion mouse models
      underscore the complexity of TGF-beta biology across the cycle of mammary
      development and differentiation. Early loss of TGF-beta growth regulation in
      breast cancer evolves into fundamental deregulation that mediates cell
      interactions and phenotypes driving invasive disease. Two outstanding issues are
      to understand the mechanisms of biological control in situ and the circumstances
      by which TGF-beta regulation is subverted in neoplastic progression.

PMID- 20810552
TI  - Use of propentofylline in feline bronchial disease: prospective, randomized,
      positive-controlled study.
AB  - Propentofylline is a methylxanthine derivative with bronchodilating actions
      similar to those of theophylline. Nineteen cats with bronchial disease were
      enrolled in this study. All cats received a low dose of prednisolone; 10 of the
      cats additionally received propentofylline. Propentofylline-treated cats
      significantly improved in their auscultation scores, respiratory pattern scores,
      and radiological bronchial markings score over the observation period, and they
      coughed less and slept less at the end of the study. No significant changes were
      noted in the control group. This study provides evidence that a combination
      therapy with prednisolone and propentofylline in cats with bronchial disease
      might be superior over monotherapy with prednisolone.

PMID- 20810553
TI  - Acute megakaryoblastic leukemia in dogs: a report of three cases and review of
      the literature.
AB  - Three dogs of different breeds, ages, and genders were presented with pale mucous
      membranes, depression, anorexia, and splenomegaly. Observed were severe
      normocytic, nor-mochromic, nonregenerative anemia, thrombocytopenia, and
      leukopenia. Blood smears contained large, atypical cells with blue vacuolated
      cytoplasm, cytoplasmic blebs, round to oval central nuclei, and elevated numbers
      of cytoplasmic fragment resembling macroplatelets. Bi- and multinucleated
      atypical cells were found mainly in spleen, lymph nodes, and bone marrow. A final
      diagnosis of acute megakaryoblastic leukemia (AMegL) was made based on morphology
      and positivity to the megakaryocyte-derived cell-specific markers von Willebrand
      factor and CD61. In case nos. 1 and 2, no treatment was initiated, and the dogs
      died on days 4 and 3, respectively. Case no. 3 received supportive therapy with
      prednisone, and after a brief improvement the dog died spontaneously 35 days
      after initial presentation. Only 11 cases of AMegL have been reported in dogs,
      and the specific diagnostic criteria have not been well established. The presence
      of vacuolization, cytoplasmic blebs, central round nuclei, cytoplasmic fragments,
      and multinucleated cells in these three cases were considered useful to
      differentiate AMegL from other hematopoietic neoplasms.

PMID- 20810554
TI  - Hemorrhagic pleural effusion secondary to an unusual type III hiatal hernia in a
      4-year-old great dane.
AB  - An unusual case of combined axial and paraesophageal (type III) hiatal hernia
      (HH) in a 4-year-old Great Dane is reported. The main presenting complaint was
      dyspnea, and no history of trauma was present. A tentative diagnosis of HH with
      secondary pleural effusion was made based on clinical signs and radiographic
      findings. Exploratory celiotomy revealed herniation of the gastric cardia,
      fundus, and body through the esophageal hiatus and an adjacent, distinct defect
      in the diaphragm. Rupture of the short gastric vessels lead to the formation of a
      hemorrhagic pleural effusion that impaired ventilation. The esophageal hiatus was
      surgically reduced in size, and the second defect was closed with nonabsorbable
      sutures. Esophagopexy and tube gastropexy procedures were also performed. The dog
      was clinically normal 9 months postoperatively. This type of HH is not currently
      defined within the traditional classification system and to the authors'
      knowledge has not been previously reported.

PMID- 20810555
TI  - Diaphragmatic support of a thoracic wall defect in a dog.
AB  - A large, caudal thoracic mass was removed along with ribs 11 and 12, resulting in
      an approximate 16 x 14-cm, caudal thoracic wall defect in a dog. The
      diaphragmatic musculature was mobilized and used to support the thoracic wall
      defect. To our knowledge, this method of thoracic wall repair has not been
      previously reported. This procedure allowed for airtight closure of the thoracic
      cavity, provided physical support, eliminated the need for muscle flaps or
      commercially available meshes, and provided a good cosmetic appearance without
      negatively affecting the dog's athletic performance.

PMID- 20810556
TI  - Feline hypertrophic osteopathy: a collection of seven cases in Taiwan.
AB  - Between October 2003 and May 2004, seven cats were diagnosed with severe and
      extensive hypertrophic osteopathy of the appendicular skeleton without detectable
      underlying causes. All cats showed similar clinical signs of pain with
      progressive lameness of the limbs. One cat died shortly after presentation,
      whereas conditions of the others resolved after medical treatment and a change in
      diet. Regression of the bone lesions was observed radiographically in all
      surviving six cases.

PMID- 20810557
TI  - Uterine rupture and septic peritonitis following dystocia and assisted delivery
      in a Great Dane bitch.
AB  - A Great Dane bitch was treated for presumed primary uterine inertia with repeated
      doses of oxytocin and manually assisted whelping. She was diagnosed with uterine
      rupture and septic peritonitis the following day. The uterine rupture is
      hypothesized to have occurred as a result of the management strategy used to
      treat dystocia. The dog underwent ovariohysterectomy, and the septic peritonitis
      was managed with open peritoneal drainage. The dog recovered well and was
      discharged 5 days later. No previous reports of canine uterine rupture associated
      with manual intervention appear to have been published. This report highlights
      the potential dangers involved in such an approach.

PMID- 20810558
TI  - Porcine small intestinal submucosa augmentation urethroplasty and balloon
      dilatation of a urethral stricture secondary to inadvertent prostatectomy in a
      dog.
AB  - A 10-month-old, male German shepherd dog experienced inadvertent prostatectomy
      during cryptorchidectomy. Cystourethral anastomosis was performed 1 day later.
      The dog developed stranguria and incontinence. A proximal urethral stricture was
      diagnosed with a contrast urethrogram 5 weeks later. Urethral augmentation with
      an onlay graft of porcine small intestinal submucosa was performed. Urinary
      diversion was accomplished with a urethral catheter followed by a cystostomy
      tube. The stricture recurred over the next 6 weeks. Three urethral balloon
      dilatations were performed 3 days apart, with the third attempt resulting in
      expansion of the stricture. Twenty-two months postdilatation, the dog
      intermittently urinated with a steady stream and had mild to moderate urinary
      incontinence.

PMID- 20810559
TI  - Aortic body tumor in full-sibling English bulldogs.
AB  - A 10-year-old, neutered male English bulldog died acutely from respiratory
      distress after a short history of progressive dyspnea. Less than 2 months later,
      a spayed female full sibling of that dog died suddenly during a nail trim. An
      aortic body tumor was the cause of death in both dogs based on postmortem and
      histological examinations. A pheochromocytoma was also diagnosed in the neutered
      male. Neither dog had a history of brachycephalic airway syndrome, and the
      implication for a genetic predisposition toward the development of paraganglioma
      is discussed. This is the first case report of aortic body tumors in sibling
      dogs, although the condition may not be an uncommon phenomenon.

PMID- 20810560
TI  - Activin A regulates porcine follicle-stimulating hormone beta-subunit
      transcription via cooperative actions of SMADs and FOXL2.
AB  - Activins stimulate FSH synthesis and secretion by pituitary gonadotrope cells.
      Activin A induction of porcine and murine FSHbeta (Fshb) gene transcription in
      immortalized gonadotropes is dependent on homolog of Drosophila mothers against
      decapentaplegic (SMAD) proteins as well as the forkhead transcription factor L2
      (FOXL2). Using both heterologous and homologous cell models, we demonstrate that
      FOXL2 functionally synergizes with SMAD3/4 to stimulate porcine Fshb promoter
      reporter activity. We further show that endogenous FOXL2 and SMAD2/3 physically
      interact in homologous cells. We identify two composite cis-elements of adjacent
      FOXL2 and SMAD binding sites in the proximal porcine Fshb promoter that mediate
      activin A, FOXL2, and SMAD3 actions. FOXL2 can bind these elements independently
      of SMADs, whereas SMAD3/4 binding requires high-affinity FOXL2 binding.
      Conversely, FOXL2 alone is insufficient to regulate Fshb transcription and
      requires SMADs to induce promoter activity. Collectively, our data suggest a
      model in which activins stimulate formation and nuclear accumulation of SMAD3/4
      complexes, which interact with FOXL2 bound to at least two proximal promoter
      elements. This association stabilizes SMAD3/4 binding to adjacent SMAD binding
      elements. SMAD-FOXL2 complexes then mediate activation of transcription through a
      currently unknown mechanism. Conservation of one of the two composite cis
      elements suggests that this may form part of a general mechanism whereby activins
      regulate Fshb subunit transcription and FSH synthesis.

PMID- 20810561
TI  - Stimulatory effect of insulin on 5alpha-reductase type 1 (SRD5A1) expression
      through an Akt-dependent pathway in ovarian granulosa cells.
AB  - Elevated levels of 5alpha-reduced androgens have been shown to be associated with
      hyperandrogenism and hyperinsulinemia, the leading causes of ovulatory
      dysfunction in women. 5alpha-Dihydrotestosterone reduces ovarian granulosa cell
      proliferation by inhibiting FSH-mediated mitogenic signaling pathways. The
      present study examined the effect of insulin on 5alpha-reductase, the enzyme that
      catalyses the conversion of androgens to their 5alpha-derivatives. Granulosa
      cells isolated from immature rat ovaries were cultured in serum-free, phenol red
      free DMEM-F12 media and treated with different doses of insulin (0, 0.1, 1.0, and
      10.0 MUg/ml) for different time intervals up to 12 h. The expression of 5alpha
      reductase type 1 mRNA, the predominant isoform found in granulosa cells, showed a
      significant (P<0.05) increase in response to the insulin treatment up to 12 h
      compared with control. The catalytic activity of 5alpha-reductase enzyme was also
      stimulated in a dose-depended manner (P<0.05). Inhibiting the Akt-dependent
      signaling pathway abolished the insulin-mediated increase in 5alpha-reductase
      mRNA expression, whereas inhibition of the ERK-dependent pathway had no effect.
      The dose-dependent increase in 5alpha-reductase mRNA expression as well as
      catalytic activity seen in response to insulin treatment was also demonstrated in
      the human granulosa cell line (KGN). In addition to increased mRNA expression, a
      dose-dependent increase in 5alpha-reductase protein expression in response to
      insulin was also seen in KGN cells, which corroborated well with that of mRNA
      expression. These results suggest that elevated levels of 5alpha-reduced
      androgens seen in hyperinsulinemic conditions might be explained on the basis of
      a stimulatory effect of insulin on 5alpha-reductase in granulosa cells. The
      elevated levels of these metabolites, in turn, might adversely affect growth and
      proliferation of granulosa cells, thereby impairing follicle growth and
      ovulation.

PMID- 20810562
TI  - Cannabinoid receptor 1 influences chromatin remodeling in mouse spermatids by
      affecting content of transition protein 2 mRNA and histone displacement.
AB  - Marijuana smokers and animals treated with Delta9-tetrahydrocannabinol, the
      principal component of marijuana, show alterations of sperm morphology suggesting
      a role for cannabinoids in sperm differentiation and/or maturation. Because the
      cannabinoid receptor 1 (CNR1) activation appears to play a pivotal role in
      spermiogenesis, the developmental stage where DNA is remodeled, we hypothesized
      that CNR1 receptors might also influence chromatin quality in sperm. We used Cnr1
      null mutant (Cnr1-/-) mice to study the possible role of endocannabinoids on
      sperm chromatin during spermiogenesis. We demonstrated that CNR1 activation
      regulated chromatin remodeling of spermatids by either increasing Tnp2 levels or
      enhancing histone displacement. Comparative analysis of wild-type, Cnr1+/-, and
      Cnr1-/- animals suggested the possible occurrence of haploinsufficiency for Tnp2
      turnover control by CNR1, whereas histone displacement was disrupted to a lesser
      extent. Furthermore, flow cytometry analysis demonstrated that the genetic loss
      of Cnr1 decreased sperm chromatin quality and was associated with sperm DNA
      fragmentation. This damage increased during epididymal transit, from caput to
      cauda. Collectively, our results show that the expression/activity of CNR1
      controls the physiological alterations of DNA packaging during spermiogenesis and
      epididymal transit. Given the deleterious effects of sperm DNA damage on male
      fertility, we suggest that the reproductive function of marijuana users may also
      be impaired by deregulation of the endogenous endocannabinoid system.

PMID- 20810563
TI  - Suppression of NF-kappaB increases bone formation and ameliorates osteopenia in
      ovariectomized mice.
AB  - Bone degenerative diseases, including osteoporosis, impair the fine balance
      between osteoclast bone resorption and osteoblast bone formation. Single-agent
      therapy for anabolic and anticatabolic effects is attractive as a drug target to
      ameliorate such conditions. Inhibition of nuclear factor (NF)-kappaB reduces the
      osteoclast bone resorption. The role of NF-kappaB inhibitors on osteoblasts and
      bone formation, however, is minimal and not well investigated. Using an
      established NF-kappaB inhibitor named S1627, we demonstrated that inhibition of
      NF-kappaB increases osteoblast differentiation and bone formation in vitro by up
      regulating the mRNAs of osteoblast-specific genes like type I collagen, alkaline
      phosphatase, and osteopontin. In addition, S1627 was able to increase bone
      formation and repair bone defect in a murine calvarial defect model. To determine
      the effect of NF-kappaB on a model of osteoporosis, we injected two doses of
      inhibitor (25 and 50 mg/kg.d) twice a day in sham-operated or ovariectomized 12
      wk-old mice and killed them after 4 wk. The anabolic effect of S1627 on
      trabecular bone was determined by micro focal computed tomography and
      histomorphometry. Bone mineral density of inhibitor-treated ovariectomized
      animals was significantly increased compared with sham-operated mice. Osteoblast
      related indices like osteoblast surface, mineral apposition rate, and bone
      formation rate were increased in S1627-treated animals in a dose-dependent
      manner. NF-kappaB inhibition by S1627 increased the trabecular bone volume in
      ovariectomized mice. Furthermore, S1627 could inhibit the osteoclast number, and
      osteoclast surface to bone surface. In vitro osteoclastogenesis and bone
      resorbing activity were dose-dependently reduced by NF-kappaB inhibitor S1627.
      Taken collectively, our results suggest that NF-kappaB inhibitors are effective
      in treating bone-related diseases due to their dual anabolic and antiresorptive
      activities.

PMID- 20810564
TI  - A novel antagonistic effect of the bone morphogenetic protein system on prolactin
      actions in regulating steroidogenesis by granulosa cells.
AB  - To investigate the mechanism by which prolactin (PRL) regulates follicular
      steroidogenesis in the ovary, we examined the functional roles of PRL in
      steroidogenesis using rat oocyte/granulosa cell coculture and focusing on the
      bone morphogenetic protein (BMP) system. The expression of long and short forms
      of PRL receptor (PRLR) were detected in both oocytes and granulosa cells, and PRL
      effectively up-regulated PRLR expression in granulosa cells in the presence of
      FSH. PRL suppressed FSH-induced estradiol production and increased FSH-induced
      progesterone production in granulosa cells. The PRL effects on FSH-induced
      progesterone were blocked by coculture with oocytes, implying roles of oocyte
      derived factors in suppression of progesterone production in PRL-exposed
      granulosa cells. In accordance with the data for steroids, FSH-induced aromatase
      expression was suppressed by PRL, whereas FSH-induced steroidogenic acute
      regulatory protein, P450scc (P450 side-chain cleavage enzyme), and 3beta
      hydroxysteroid dehydrogenase type 2 levels were amplified by PRL. However,
      forskolin- and N(6),O(2)-dibutyryl cAMP-induced steroid levels and FSH- and
      forskolin-induced cAMP were not affected by PRL, suggesting that PRL action on
      FSH-induced steroidogenesis was not due to cAMP-protein kinase A regulation.
      Treatment with a BMP-binding protein, noggin, facilitated PRL-induced estradiol
      reduction, and noggin increased PRL-induced progesterone production in FSH
      treated granulosa cells cocultured with oocytes, suggesting that endogenous BMPs
      reduce progesterone but increase estradiol when exposed to high concentrations of
      PRL. PRL increased the expression of BMP ligands in oocyte/granulosa cell
      coculture and augmented BMP-induced phosphorylated mothers against
      decapentaplegic 1/5/8 signaling by reducing inhibitory phosphorylated mothers
      against decapentaplegic 6 expression through the Janus kinase/signal transducer
      and activator of transcription (STAT) pathway. In addition to STAT activation,
      PRL enhanced FSH-induced MAPK phosphorylation in granulosa cells, in which ERK
      activation was preferentially involved in suppression of FSH-induced estradiol.
      Furthermore, noggin treatment enhanced PRLR signaling including MAPK and STAT.
      Considering that BMPs suppressed PRLR in granulosa cells, it is likely that the
      BMP system in growing follicles plays a key role in antagonizing PRLR signaling
      actions in the ovary exposed to high concentrations of PRL.

PMID- 20810565
TI  - Peroxisomal localization of the proopiomelanocortin-derived peptides beta
      lipotropin and beta-endorphin.
AB  - The peptide hormones ACTH, MSHs, beta-lipotropin (beta-LPH), and beta-endorphin
      are all derived from the precursor molecule proopiomelanocortin (POMC). Using
      confocal laser microscopy and immunoelectron microscopy in human pituitary gland,
      we demonstrate a peroxisomal localization of beta-endorphin and beta-LPH in cells
      expressing the peroxisomal ATP-binding cassette-transporter adrenoleukodystrophy
      protein (ALDP). The peroxisomal localization of beta-LPH and beta-endorphin was
      not restricted to the pituitary gland but was additionally found in other human
      tissues that express high levels of ALDP, such as dorsal root ganglia, adrenal
      cortex, distal tubules of kidney, and skin. In contrast to the peptide hormones
      beta-LPH and beta-endorphin, which are derived from the C terminus of POMC, the N
      terminal peptides ACTH, alpha-MSH, and gamma-MSH were never detected in
      peroxisomes. This novel peroxisomal localization of beta-endorphin and beta-LPH
      in ALDP-positive cells was confirmed by costaining with ALDP and the peroxisomal
      marker catalase. Moreover, peroxisomal sorting of beta-LPH could be modeled in
      HeLa cells by ectopic expression of a POMC variant, modified to allow cleavage
      and release of beta-LPH within the secretory pathway. Although beta-LPH and beta
      endorphin were only associated with peroxisomes in cells that normally express
      ALDP, the transporter activity of ALDP is not necessary for the peroxisomal
      localization, as demonstrated in tissues of X-linked adrenoleukodystrophy
      patients lacking functional ALDP. It remains to be elucidated whether and how the
      peroxisomal localization of POMC-derived hormones has a role in the endocrine
      dysfunction of peroxisomal disease.

PMID- 20810566
TI  - PPARgamma in placental angiogenesis.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear
      receptor involved in diverse biological processes including adipocyte
      differentiation, glucose homeostasis, and inflammatory responses. Analyses of
      PPARgamma knockout animals have been so far preempted by the early embryonic
      death of PPARgamma-/- embryos as a consequence of the severe alteration of their
      placental vasculature. Using Sox2Cre/PPARgammaL2/L2 mice, we obtained fully
      viable PPARgamma-null mice through specific and total epiblastic gene deletion,
      thereby demonstrating that the placental defect is the unique cause of PPARgamma
      /- embryonic lethality. The vasculature defects observed in PPARgamma-/-
      placentas at embryonic d 9.5 correlated with an unsettled balance of pro- and
      antiangiogenic factors as demonstrated by increased levels of proliferin (Prl2c2,
      PLF) and decreased levels of proliferin-related protein (Prl7d1, PRP),
      respectively. To analyze the role of PPARgamma in the later stage of placental
      development, when its expression peaks, we treated pregnant wild-type mice with
      the PPARgamma agonist rosiglitazone. This treatment resulted in a disorganization
      of the placental layers and an altered placental microvasculature, accompanied by
      the decreased expression of proangiogenic genes such as Prl2c2, vascular
      endothelial growth factor, and Pecam1. Together our data demonstrate that
      PPARgamma plays a pivotal role in controlling placental vascular proliferation
      and contributes to its termination in late pregnancy.

PMID- 20810567
TI  - Differential role of PKC isoforms in GnRH and phorbol 12-myristate 13-acetate
      activation of extracellular signal-regulated kinase and Jun N-terminal kinase.
AB  - GnRH is the first key hormone of reproduction. The role of protein kinase C (PKC)
      isoforms in GnRH-stimulated MAPK [ERK and Jun N-terminal kinase (JNK)] was
      examined in the alphaT3-1 and LbetaT2 gonadotrope cells. Incubation of the cells
      with GnRH resulted in a protracted activation of ERK1/2 and a slower and more
      transient activation of JNK1/2. Gonadotropes express conventional PKCalpha and
      conventional PKCbetaII, novel PKCdelta, novel PKCepsilon, and novel PKCtheta, and
      atypical PKC-iota/lambda. The use of green fluorescent protein-PKC constructs
      revealed that GnRH induced rapid translocation of PKCalpha and PKCbetaII to the
      plasma membrane, followed by their redistribution to the cytosol. PKCdelta and
      PKCepsilon localized to the cytoplasm and Golgi, followed by the rapid
      redistribution by GnRH of PKCdelta to the perinuclear zone and of PKCepsilon to
      the plasma membrane. Interestingly, PKCalpha, PKCbetaII, and PKCepsilon
      translocation to the plasma membrane was more pronounced and more prolonged in
      phorbol-12-myristate-13-acetate (PMA) than in GnRH-treated cells. The use of
      selective inhibitors and dominant-negative plasmids for the various PKCs has
      revealed that PKCbetaII, PKCdelta, and PKCepsilon mediate ERK2 activation by
      GnRH, whereas PKCalpha, PKCbetaII, PKCdelta, and PKCepsilon mediate ERK2
      activation by PMA. Also, PKCalpha, PKCbetaII, PKCdelta, and PKCepsilon are
      involved in GnRH and PMA stimulation of JNK1 in a cell-context-dependent manner.
      We present preliminary evidence that persistent vs. transient redistribution of
      selected PKCs or redistribution of a given PKC to the perinuclear zone vs. the
      plasma membrane may dictate its selective role in ERK or JNK activation. Thus, we
      have described the contribution of selective PKCs to ERK and JNK activation by
      GnRH.

PMID- 20810568
TI  - Detailed molecular fingerprinting of four new anaplastic thyroid carcinoma cell
      lines and their use for verification of RhoB as a molecular therapeutic target.
AB  - CONTEXT: Anaplastic thyroid carcinoma (ATC) is a highly aggressive carcinoma in
      need of therapeutic options. One critical component of drug discovery is the
      availability of well-characterized cell lines for identification of molecular
      mechanisms related to tumor biology and drug responsiveness. Up to 42% of human
      thyroid cancer cell lines are redundant or not of correct tissue origin, and a
      comprehensive analysis is currently nonexistent. Mechanistically, RhoB has been
      identified as a novel molecular target for ATC therapy. OBJECTIVE: The aim was to
      develop four ATC cell lines detailing genetic, molecular, and phenotypic
      characteristics and to test five classes of drugs on the cell lines to determine
      whether they inhibited cell proliferation in a RhoB-dependent fashion. DESIGN:
      Four cell lines were derived from ATC tumors. Short tandem DNA repeat and
      mutational status of the originating tumors and cell lines were performed along
      with molecular and phenotypic characterizations. Compounds were tested for growth
      inhibition and ability to up-regulate RhoB. RESULTS: Cell line authenticity was
      confirmed by DNA short tandem repeat analysis. Each proved unique regarding
      expression of thyroid markers, oncogene status, amplified and deleted genes, and
      proliferative growth rates. FTI-277, GGTI-286, lovastatin, romidepsin, and UCN-01
      up-regulated RhoB and inhibited cell proliferation in a dose-responsive fashion
      with only romidepsin and FTI-277 being RhoB dependent. CONCLUSIONS: Molecular
      descriptions of thyroid lines were matched to the originating tumors, setting a
      new standard for cell line characterization. Furthermore, suppressed RhoB is
      implicated as a molecular target for therapy against ATC because five classes of
      drugs up-regulate RhoB and inhibit growth dose-responsively.

PMID- 20810569
TI  - Neonatal diabetes caused by mutations in sulfonylurea receptor 1: interplay
      between expression and Mg-nucleotide gating defects of ATP-sensitive potassium
      channels.
AB  - CONTEXT: ATP-sensitive potassium (KATP) channels regulate insulin secretion by
      coupling glucose metabolism to beta-cell membrane potential. Gain-of-function
      mutations in the sulfonylurea receptor 1 (SUR1) or Kir6.2 channel subunit
      underlie neonatal diabetes. OBJECTIVE: The objective of the study was to
      determine the mechanisms by which two SUR1 mutations, E208K and V324M, associated
      with transient neonatal diabetes affect KATP channel function. DESIGN: E208K or
      V324M mutant SUR1 was coexpressed with Kir6.2 in COS cells, and expression and
      gating properties of the resulting channels were assessed biochemically and
      electrophysiologically. RESULTS: Both E208K and V324M augment channel response to
      MgADP stimulation without altering sensitivity to ATP4- or sulfonylureas.
      Surprisingly, whereas E208K causes only a small increase in MgADP response
      consistent with the mild transient diabetes phenotype, V324M causes a severe
      activating gating defect. Unlike E208K, V324M also impairs channel expression at
      the cell surface, which is expected to dampen its functional impact on beta
      cells. When either mutation was combined with a mutation in the second nucleotide
      binding domain of SUR1 previously shown to abolish Mg-nucleotide response, the
      activating effect of E208K and V324M was also abolished. Moreover, combination of
      E208K and V324M results in channels with Mg-nucleotide sensitivity greater than
      that seen in individual mutations alone. CONCLUSION: The results demonstrate that
      E208K and V324M, located in distinct domains of SUR1, enhance transduction of Mg
      nucleotide stimulation from the SUR1 nucleotide binding folds to Kir6.2.
      Furthermore, they suggest that diabetes severity is determined by interplay
      between effects of a mutation on channel expression and channel gating.

PMID- 20810570
TI  - The Swiss iodized salt program provides adequate iodine for school children and
      pregnant women, but weaning infants not receiving iodine-containing complementary
      foods as well as their mothers are iodine deficient.
AB  - BACKGROUND: If children and pregnant women in the population are iodine
      sufficient, it is generally assumed infants are also sufficient. But weaning
      infants may be at risk of iodine deficiency because iodized salt contributes
      little dietary iodine during this period. To fill this gap, iodine fortification
      of infant formula milk (IFM) and complementary foods (CF) is likely important.
      OBJECTIVES: The objective of the study was to first confirm that Swiss school
      children and pregnant women remain iodine sufficient and then to assess iodine
      status in infancy and the relative contribution of breast milk and IFM/CF to
      their iodine intakes. METHODS: We measured urinary iodine concentrations (UIC) in
      national cross-sectional samples of: 1) pregnant women (n=648); 2) school
      children (n=916); 3) infants at three time points: at 3-4 d after birth and at 6
      and 12 months (n=875); and 4) breast-feeding mothers (n=507). We measured breast
      milk iodine concentrations in the mothers, assessed iodine sources in infant
      diets, and analyzed iodine content of commercial IFM/CFs (n=22) and salt samples
      from the school children's households (n=266). RESULTS: Median (m) UICs in
      pregnant women (162 MUg/liter) and school children (120 MUg/liter) were
      sufficient, and 80% of the household salt was adequately iodized (>=15 ppm).
      However, mUICs in infants not receiving IFM/CF were not sufficient: 1) mUIC in
      breast-fed infants (82 MUg/liter) was lower than in non-breast-fed infants (105
      MUg/liter) (P<0.001) and 2) mUIC in breast-fed weaning infants not receiving
      IFM/CF (70 MUg/liter) was lower than infants receiving IFM (109 MUg/liter)
      (P<0.01). mUIC was low in lactating mothers (67 MUg/liter) and median breast milk
      iodine concentration was 49 MUg/kg. CONCLUSIONS: In countries in which iodized
      salt programs supply sufficient iodine to older children and pregnant women,
      weaning infants, particularly those not receiving iodine-containing IFM, may be
      at risk of inadequate iodine intakes.

PMID- 20810571
TI  - CXCL9 and CXCL11 chemokines modulation by peroxisome proliferator-activated
      receptor-alpha agonists secretion in Graves' and normal thyrocytes.
AB  - CONTEXT: Peroxisome proliferator-activated receptor (PPAR)-alpha has been shown
      to exert immunomodulatory effects in autoimmune disorders. However, until now, no
      data were present in the literature about the effect of PPARalpha activation on
      CXCL9 and CXCL11 chemokines in general or on secretion of these chemokines in
      thyroid cells. OBJECTIVE AND DESIGN: The presence of PPARalpha and PPARgamma has
      been evaluated by real-time-PCR in Graves' disease (GD) and control cells in
      primary culture. Furthermore, we have tested the role of PPARalpha and PPARgamma
      activation on CXCL9 and CXCL11 secretion in GD and control cells after
      stimulation of these chemokines secretion with IFNgamma and TNFalpha. RESULTS:
      This study shows the presence of PPARalpha and PPARgamma in GD and control cells.
      A potent dose-dependent inhibition by PPARalpha-agonists was observed on the
      cytokines-stimulated secretion of CXCL9 and CXCL11 in GD and control cells. The
      potency of the PPARalpha agonists used was maximum on the secretion of CXCL9,
      reaching about 90% of inhibition by fenofibrate and 85% by ciprofibrate. The
      relative potency of the compounds was different with each chemokine; for example,
      gemfibrozil exerted a 55% inhibition on CXCL11, whereas it had a weaker activity
      on CXCL9 (40% inhibition). PPARalpha agonists were stronger (ANOVA, P<0.001)
      inhibitors of CXCL9 and CXCL11 secretion in thyrocytes than PPARgamma agonists.
      CONCLUSIONS: Our study shows the presence of PPARalpha in GD and control
      thyrocytes. PPARalpha activators are potent inhibitors of the secretion of CXCL9
      and CXCL11, suggesting that PPARalpha may be involved in the modulation of the
      immune response in the thyroid.

PMID- 20810572
TI  - Real-time elastosonography: useful tool for refining the presurgical diagnosis in
      thyroid nodules with indeterminate or nondiagnostic cytology.
AB  - BACKGROUND: Indeterminate and nondiagnostic patterns represent the main
      limitation of fine-needle aspiration (FNA) cytology of thyroid nodules, clinical
      and echographic features being poorly predictive of malignancy. The newly
      developed real-time ultrasound elastography (USE) has been previously applied to
      differentiate malignant from benign lesions. The aim of this study was to get
      further insights into the role of USE in the presurgical diagnosis of nodules
      with indeterminate or nondiagnostic cytology. PATIENTS: The study included 176
      patients who had one (n=138) or multiple (n=38) nodules with indeterminate or
      nondiagnostic cytology on FNA, for whom histology was available after
      thyroidectomy. A total of 195 nodules (142 indeterminate, 53 nondiagnostic) were
      submitted to USE, and elasticity was scored as 1 (high), 2 (intermediate), or 3
      (low). RESULTS: In indeterminate lesions, the score 1, describing high
      elasticity, was strongly predictive of benignity, being found in 102 of 111
      benign nodules and in only one of 31 carcinomas (P<0.0001). By combining the
      scores 2 and 3, USE had a sensitivity of 96.8% and a specificity of 91.8%. In
      nodules with nondiagnostic cytology, score 1 was found in 39 of 45 benign nodules
      and in only one of eight carcinomas (P<0.0001). By combining the scores 2 and 3,
      USE had a sensitivity of 87.5% and a specificity of 86.7%. CONCLUSIONS: USE may
      represent an important tool for the diagnosis of thyroid cancer in nodules with
      indeterminate or nondiagnostic cytology and may prove useful in selecting
      patients who are candidates for surgery.

PMID- 20810574
TI  - Normal cortisol response on low-dose synacthen (1 microg) test in children with
      Prader Willi syndrome.
AB  - INTRODUCTION: It has been postulated that central adrenal insufficiency (CAI),
      resulting from hypothalamic dysfunction, may contribute to the increased
      unexplained death rates in Prader Willi syndrome (PWS). A study using the
      overnight metyrapone test reported a 60% prevalence of CAI in children with PWS.
      We used a low-dose Synacthen test to screen for CAI in children with PWS.
      METHODS: We studied 41 children with genetic diagnosis of PWS [20 males; mean
      age, 7.68 (+/-5.23) yr] in five pediatric endocrinology centers in Australasia.
      All participants were randomly selected, and none had a history of Addisonian
      crisis. Ten of the cohort were receiving sex hormone therapy, 19 were receiving
      GH, and four were receiving T4. Their mean body mass index z-score was +1.48 (+/
      1.68). Baseline morning ACTH and cortisol levels were measured, followed by iv
      administration of 1 MUg Synacthen. Post-Synacthen cortisol levels were measured
      at 30 min, and a cortisol level above 500 nmol/liter was considered normal.
      RESULTS: The mean baseline ACTH and cortisol were 15 (+/-14) ng/liter and 223 (+/
      116) nmol/liter, respectively. The mean 30-min plasma cortisol was 690 (+/-114)
      nmol/liter, and the average increase from baseline was 201%. CONCLUSIONS: Our
      result suggests that CAI is rare in children with PWS.

PMID- 20810573
TI  - Ethnic differences in the relationship between pericardial adipose tissue and
      coronary artery calcified plaque: African-American-diabetes heart study.
AB  - BACKGROUND: Calcified atherosclerotic plaque (CP) is less prevalent and less
      severe in African-Americans (AA), relative to European Americans (EA). Because
      pericardial adipose tissue (PAT) is associated with CP in the neighboring
      coronary arteries, we explored ethnic-specific relationships between PAT and CP.
      METHODS: PAT volume and coronary and aortic CP were measured in 561 EA and 575 AA
      subjects with type 2 diabetes using single and multidetector computed tomography.
      Generalized estimating equations with exchangeable correlation and the sandwich
      estimator of the variance were used to test for associations between PAT and CP.
      RESULTS: Mean (sd) ages of AA and EA participants were 56.7 (9.5) and 62.0 (8.9)
      yr, respectively; diabetes duration was 10.5 (8.1) and 10.1 (7.3) yr; and PAT
      volume was 86.9 (38.6) and 131.7 (55.3) cm3/45 mm. In AA and EA participants,
      respectively, mean (sd) coronary CP mass scores were 803 (1,889) and 1,465
      (2,847) mg calcium; and aortic CP, 5,407 (10,651) and 10,090 (15,087) mg calcium.
      Adjusting for age, gender, body mass index, blood pressure, height, smoking,
      lipid-lowering medications, C-reactive protein, albuminuria, high-density
      lipoprotein-cholesterol, and triglycerides, parameter estimates for the
      relationship between PAT and log(coronary CP+1) were 0.012 in AA (P<0.0001) and
      0.003 (P=0.24) in EA, with a significant ethnic difference (P=0.019). No
      significant relationships or ethnic differences were observed between PAT and
      aortic CP (P=0.24, fully adjusted model). CONCLUSIONS: Pericardial adiposity is
      strongly associated with coronary atherosclerosis in AA with type 2 diabetes.
      Novel cardiovascular disease risk factors such as PAT may contribute to ethnic
      disparities in susceptibility to development of coronary atherosclerosis.

PMID- 20810575
TI  - The pharmacological characteristics of molecular-based inherited salt-losing
      tubulopathies.
AB  - CONTEXT: Our understanding of inherited salt-losing tubulopathies has improved
      with recent advances in molecular genetics. However, the terminology of Bartter
      syndrome and Gitelman syndrome does not always accurately reflect their
      pathophysiological basis or clinical presentation, and some patients are
      difficult to diagnose from their clinical presentations. OBJECTIVE: In the
      present study, we conducted molecular analysis and diuretic tests for patients
      with inherited salt-losing tubulopathies to clarify the pharmacological
      characteristics of these disorders. PATIENTS: We detected mutations and
      subsequently conducted diuretic tests using furosemide and thiazide for 16
      patients with salt-losing tubulopathies (two with SLC12A1; two with KCNJ1; nine
      with CLCNKB; and three with SLC12A3). RESULTS: Patients with SLC12A1 mutations
      showed no response to furosemide, whereas those with SLC12A3 mutations showed no
      response to thiazide. However, patients with CLCNKB mutations showed no response
      to thiazide and a normal response to furosemide, and those with KCNJ1 mutations
      showed a good response to both diuretics. This study revealed the following
      characteristics of these disorders: 1) subjects with CLCNKB mutations showed one
      or more biochemical features of Gitelman syndrome (including hypomagnesemia,
      hypocalciuria, and fractional chloride excretion insensitivity to thiazide
      administration); and 2) subjects with KCNJ1 mutations appeared to show normal
      fractional chloride excretion sensitivity to furosemide and thiazide
      administration. CONCLUSIONS: These results indicate that these disorders are
      difficult to distinguish in some patients, even when using diuretic challenge.
      This clinical report provides important findings that can improve our
      understanding of inherited salt-losing tubulopathies and renal tubular
      physiology.

PMID- 20810576
TI  - Insulin-like growth factor-I in cord blood is predictive of catch-up growth in
      monozygotic twins with discordant growth.
AB  - OBJECTIVE: The aim was to investigate the growth of monozygotic twins with
      discordant birth weights and the predictive value of birth-weight, birth-length,
      and cord-blood concentration of growth factors on their catch-up growth up to the
      age of 4 yr. PATIENTS AND METHODS: Twenty-five monozygotic twin-pairs [14 with an
      intertwin birth-weight sd score (SDS) difference>1] were studied at birth and at
      4 yr of age. In all pairs, several parameters including IGF-I were analyzed in
      cord blood, and in 20 pairs parameters were analyzed again at 4 yr of age.
      Intertwin differences (Delta) in birth weight, birth length, and growth at 3, 6,
      12, 24, and 48 months were correlated with Delta of the parameters analyzed.
      RESULTS: We found a reduction of Delta height SDS from birth to 4 yr, with the
      main catch-up occurring during the first year, but only a slight, statistically
      insignificant reduction of Delta body mass index SDS during the observation
      period. Correlation coefficients were used to identify factors predicting
      postnatal catch-up growth. Both birth-weight difference (r=0.653; P=0.001) and
      Delta IGF-I in cord blood (r=0.613; P=0.007) were of similar predictive value.
      Variance analysis showed no significant difference in individual impact between
      these two parameters, although both correlated strongly with actual height.
      CONCLUSION: We observed a gradual convergence in height but not body mass index
      up to the age of 4 yr between genetically identical twins with discordant birth
      weights. Both birth-weight and cord-blood IGF-I are predictive of subsequent
      catch-up growth.

PMID- 20810577
TI  - Selenium and the thyroid: a close-knit connection.
AB  - CONTEXT: The recent recognition that the essential trace element selenium is
      incorporated as selenocysteine in all three deiodinases has decisively confirmed
      the clear-cut link between selenium and thyroid function. It has additionally
      been established that the thyroid contains more selenium than any other tissue
      and that selenium deficiency aggravates the manifestation of endemic myxedematous
      cretinism and autoimmune thyroid disease. EVIDENCE ACQUISITION: Clinical reports
      as well as a large number of biochemical articles linking selenium to thyroid
      have been considered. Interventional, prospective, randomized, controlled
      studies, including large observational studies, supplementing selenium in
      autoimmune thyroid disease, together with review articles published in Medline
      and Pubmed have undergone scrutiny. The methodological differences and variety of
      results emerging from these trials have been analyzed. EVIDENCE SYNTHESIS:
      Evidence in support of selenium supplementation in thyroid autoimmune disease is
      evaluated, the results herein presented demonstrating the potential effectiveness
      of selenium in reducing the antithyroid peroxidase titer and improving the
      echostructure in the ultrasound examination. However, considerable discord
      remains as to who should comprise target groups for selenium treatment, who will
      most benefit from such treatment, the precise impact of the basal antithyroid
      peroxidase level, and the effect of disease duration on the treatment outcome.
      Clearly, further in-depth studies and evaluation are required concerning the
      mechanism of action of selenium as well as the choice of supplements or dietary
      intake. CONCLUSIONS: Maintenance of "selenostasis" via optimal intake not only
      aids preservation of general health but also contributes substantially to the
      prevention of thyroid disease.

PMID- 20810579
TI  - Half full or half empty?

PMID- 20810578
TI  - Metabolic syndrome, its components, and mortality in the elderly.
AB  - CONTEXT AND OBJECTIVE: The metabolic syndrome (MetS) has been shown to predict
      mortality in the middle-aged, but less is known on the impact of MetS and its
      components on mortality risk in the elderly. Our objectives were 1) to examine
      the association of MetS with the risk of all-cause and cause-specific mortality
      in a French elderly community-dweller cohort and 2) to determine the main
      components driving these associations. PARTICIPANTS AND METHODS: Prospective
      analyses were carried out on 7118 men and women aged 65 yr and over from the
      Three-City cohort. Association between MetS (defined using the National
      Cholesterol Education Program Adult Treatment Panel III criteria) and mortality
      risk over the 7-yr follow-up was assessed using Cox proportional hazards models.
      RESULTS: After adjusting for sociodemographic variables, health behaviors, and
      health status, a 50% increased risk for all-cause mortality was observed in
      participants with MetS at baseline compared with those without, with a hazard
      ratio of 1.54 [95% confidence interval (CI) = 1.24-1.92]. Elevated fasting blood
      glucose, high triglycerides, and low high-density lipoprotein cholesterol were
      the major contributors to this association, acting synergistically on mortality
      risk. For coronary heart disease mortality and cancer mortality, the hazard
      ratios associated with MetS were 2.21 (95% CI = 1.07-4.55) and 1.49 (95% CI =
      1.04-2.14), respectively. CONCLUSIONS: By showing that an elevated fasting blood
      glucose potentiates the excess mortality risk associated with lipid abnormality,
      our study supports the status of MetS as a risk factor for mortality in the
      elderly. Our findings emphasize the importance of MetS screening and managing
      dyslipidemia and hyperglycemia in older persons in general practice.

PMID- 20810581
TI  - Mental health reforms in Europe: challenges of postgraduate psychiatric training
      in Europe: a trainee perspective.
AB  - The European Federation of Psychiatric Trainees (EFPT) is an umbrella
      organization for trainee associations in 31 countries. A survey asked member
      countries about the three most important issues facing postgraduate training.
      Qualitative analysis grouped responses in five categories: implementation of new
      postgraduate curricula, poor working conditions, low recruitment of psychiatric
      trainees, insufficient training opportunities, and inadequate psychotherapy
      training. Disparities between countries lead to trainee migration, which worsens
      conditions in their home countries. The EFPT is in a unique position to obtain
      feedback and work with partner organizations to improve the standards of
      psychiatric training for European trainees.

PMID- 20810580
TI  - Datapoints: self-reported unmet need for mental health care after California's
      parity legislation.

PMID- 20810582
TI  - Best practices: disseminating best practices for bipolar disorder treatment in a
      correctional population.
AB  - Use of medication treatment algorithms may facilitate clinical decision making,
      improve consistency, and reduce polypharmacy in the correctional setting. A
      feasibility study was conducted investigating use of Texas Implementation of
      Medication Algorithms (TIMA) guidelines for bipolar disorder in the Connecticut
      Department of Correction. Forty inmates with diagnoses of bipolar disorder were
      treated over a 12-week period adhering to the TIMA algorithm for bipolar
      disorder. Significant improvement was seen in the primary and secondary outcome
      measures (p<.001). This pilot project confirmed the feasibility of algorithm
      adaptation to the correctional setting and provided specific recommendations for
      successful dissemination of the TIMA algorithm for bipolar disorder in
      correctional settings.

PMID- 20810583
TI  - Focus on patient management: responsibly managing psychiatric inpatient refusal
      of medical or surgical diagnostic work-up.
AB  - This column uses the tools of normative ethics-analysis and argument-to provide a
      reasoned account of and to identify ethically justified responses by the
      psychiatrist to psychiatric inpatients' refusal of medical or surgical diagnostic
      work-up. There are three relevant ethical considerations when psychiatric
      inpatients refuse medical or surgical diagnostic tests: balancing autonomy with
      beneficence, surrogate decision making and confidentiality, and managing strong
      feelings. Assisted decision making and assent are key management strategies for
      promoting patients' autonomy and for protecting against adverse consequences of
      decision making.

PMID- 20810584
TI  - Medicaid beneficiaries using mental health or substance abuse services in fee-for
      service plans in 13 states, 2003.
AB  - OBJECTIVE: This study identified Medicaid beneficiaries using mental health or
      substance abuse services in fee-for-service plans in 13 states in 2003
      (N=1,380,190) and examined their use of medical services. METHODS: Administrative
      and fee-for-service claims data from Medicaid Analytic eXtract files were
      analyzed to identify mutually exclusive groups of beneficiaries who used either
      mental health or substance abuse services and to describe patterns of medical
      service use. RESULTS: Overall, 11.7% of Medicaid beneficiaries were identified as
      using mental health or substance abuse services (10.9% and .7% used each of these
      services, respectively), with substantial variation across age and eligibility
      groups. Among beneficiaries using mental health services, 47.4% had visited an
      emergency room for any reason, 7.8% were treated for their disorder in inpatient
      settings, 13.8% received inpatient treatment for problems other than their mental
      or substance use disorders, and 70.4% received prescriptions for psychotropic
      medications. Among beneficiaries using substance abuse services, 60.7% had
      visited an emergency room, 12.6% were treated for their disorder in inpatient
      settings, 24.7% received other inpatient treatment, and 46.1% received
      prescriptions for psychotropic medications. Among beneficiaries not using either
      mental health or substance use services, 29.0% had visited an emergency room,
      12.7% received inpatient treatment, and 10.1% received prescriptions for
      psychotropic medications. CONCLUSIONS: Beneficiaries who used mental health or
      substance abuse services entered general inpatient settings and visited emergency
      rooms more frequently than other beneficiaries.

PMID- 20810585
TI  - Trends in the duration of emergency department visits, 2001-2006.
AB  - OBJECTIVE: This study estimated trends in the duration of emergency department
      visits from 2001 to 2006 and compared duration by presenting complaint-mental
      health related or non-mental health related. METHODS: Data on visits (N=193,077)
      were from the National Hospital Ambulatory Medical Care Survey Emergency
      Department databases. Visits were classified as mental health visits if the
      primary reason for the visit was a common mental health symptom or disorder, a
      problem related to substance use, suicidal behaviors, or a need for counseling.
      Regression models were adjusted for year, diagnosis type, discharge status,
      payment source, demographic characteristics, receipt of medical care during the
      visit, mode of arrival, and immediacy of need for treatment. RESULTS: The
      duration of all emergency department visits increased at an annual rate of 2.3%.
      Trends were similar for mental health visits and non-mental health visits.
      Throughout the period the average duration of mental health visits exceeded the
      average duration of non-mental health visits by 42% (p<.001). This difference was
      related to the longer durations of mental health visits ending in transfer and
      visits by persons with serious mental illness or substance use disorders.
      CONCLUSIONS: From 2001 to 2006, the duration of emergency department visits made
      by patients presenting with mental health complaints and visits made by all other
      patients increased at similar rates. However, the longer visits for certain
      groups of mental health patients suggest that emergency departments incur higher
      costs in connection with the delivery of services to persons in need of acute
      stabilization.

PMID- 20810587
TI  - Findings of a U.S. national cardiometabolic screening program among 10,084
      psychiatric outpatients.
AB  - OBJECTIVE: A national cardiometabolic screening program for patients in a variety
      of public mental health facilities, group practices, and community behavioral
      health clinics was funded by Pfizer Inc. between 2005 and 2008. METHODS: A one
      day, voluntary metabolic health fair in the United States offered patients
      attending public mental health clinics free cardiometabolic screening and same
      day feedback to physicians from a biometrics testing third party that was
      compliant with the Health Insurance Portability and Accountability Act. RESULTS:
      This analysis included 10,084 patients at 219 sites; 2,739 patients (27%)
      reported having fasted for over eight hours. Schizophrenia or bipolar disorder
      was self-reported by 6,233 (62%) study participants. In the overall sample, the
      mean waist circumference was 41.1 inches for men and 40.4 inches for women; 27%
      were overweight (body mass index [BMI] 25.0-29.9 kg/m(2)), 52% were obese (BMI
      >or=30.0 kg/m(2)), 51% had elevated triglycerides (>or=150 mg/dl), and 51% were
      hypertensive (>or=130/85 mm Hg). In the fasting sample, 52% had metabolic
      syndrome, 35% had elevated total cholesterol (>or=200 mg/dl), 59% had low levels
      of high-density lipoprotein cholesterol (<40 mg/dl for men or <50 mg/dl for
      women), 45% had elevated triglycerides (>or=150 mg/dl), and 33% had elevated
      fasting glucose (>or=100 mg/dl). Among the 1,359 fasting patients with metabolic
      syndrome, 60% were not receiving any treatment. Among fasting patients who
      reported treatment for specific metabolic syndrome components, 33%, 65%, 71%, and
      69% continued to have elevated total cholesterol, low levels of high-density
      lipoprotein, high blood pressure, and elevated glucose levels, respectively.
      CONCLUSIONS: The prevalence of metabolic syndrome and cardiometabolic risk
      factors, such as overweight, hypertension, dyslipidemia, and glucose
      abnormalities, was substantial and frequently untreated in this U.S. national
      mental health clinic screening program.

PMID- 20810586
TI  - Assessing the STIRR model of best practices for blood-borne infections of clients
      with severe mental illness.
AB  - OBJECTIVES: People with co-occurring severe mental illness and a substance use
      disorder are at markedly elevated risk of infection from HIV, hepatitis B virus
      (HBV), and hepatitis C virus (HCV), but they generally do not receive basic
      recommended screening or preventive and treatment services. Barriers to services
      include lack of programs offered by mental health providers and client refusal of
      available services. Clients from racial-ethnic minority groups are even less
      likely to accept recommended services. The intervention tested was designed to
      facilitate integrated infectious disease programming in mental health settings
      and to increase acceptance of such services among clients. METHODS: A randomized
      controlled trial (N=236) compared enhanced treatment as usual (control) with a
      brief intervention to deliver best-practice services for blood-borne diseases in
      an urban sample of clients with co-occurring disorders who were largely from
      racial-ethnic minority groups. The "STIRR" intervention included Screening for
      HIV and HCV risk factors, Testing for HIV and hepatitis, Immunization against
      hepatitis A and B, Risk reduction counseling, and medical treatment Referral and
      support at the site of mental health care. RESULTS: Clients randomly assigned to
      the STIRR intervention had high levels (over 80%) of participation and acceptance
      of core services. They were more likely to be tested for HBV and HCV, to be
      immunized against hepatitis A virus and HBV, and to increase their knowledge
      about hepatitis and reduce their substance abuse. However, they showed no
      reduction in risk behavior, were no more likely to be referred to care, and
      showed no increase in HIV knowledge. Intervention costs were $541 per client
      (including $234 for blood tests). CONCLUSIONS: STIRR appears to be efficacious in
      providing a basic, best-practice package of interventions for clients with co
      occurring disorders.

PMID- 20810588
TI  - Effects of adopting a smoke-free policy in state psychiatric hospitals.
AB  - OBJECTIVE: The aim of this study was to investigate how adopting a smoke-free
      policy in state psychiatric hospitals affected key factors, including adverse
      events, smoking cessation treatment options, and specialty training for clinical
      staff about smoking-related issues. METHODS: Hospitals were surveyed in 2006 and
      2008 about their smoking policies, smoking cessation aids, milieu management,
      smoking cessation treatment options, and aftercare planning and referrals for
      smoking education. Comparisons were made between hospitals that went smoke-free
      between the two time periods (N=28) and those that did not (N=42). RESULTS: Among
      hospitals that changed to a smoke-free policy, the proportion that reported
      adverse events decreased by 75% or more in three areas: smoking or tobacco use as
      a precursor to incidents that led to seclusion or restraint, smoking-related
      health conditions, and coercion or threats among patients and staff. Hospitals
      that did not adopt a smoke-free policy cited several barriers, including
      resistance from staff, patients, and advocates. CONCLUSIONS: Although staff were
      concerned that implementing a smoke-free policy would have negative effects, this
      was not borne out. Findings indicated that adopting a smoke-free policy was
      associated with a positive impact on hospitals, as evidenced by a reduction in
      negative events related to smoking. After adoption of a smoke-free policy, fewer
      hospitals reported seclusion or restraint related to smoking, coercion, and
      smoking-related health conditions, and there was no increase in reported
      elopements or fires. For hospitals adopting a smoke-free policy in 2008, there
      was no significant difference between 2006 and 2008 in the number offering
      nicotine replacement therapies or clinical staff specialty training. Results
      suggest that smoking cessation practices are not changing in the hospital as a
      result of a change in policy.

PMID- 20810589
TI  - Self-help and community mental health agency outcomes: a recovery-focused
      randomized controlled trial.
AB  - OBJECTIVE: Self-help agencies (SHAs) are consumer-operated service organizations
      managed as participatory democracies. Members are involved in all aspects of
      organizational management, because a premise of SHAs is that organizationally
      empowered individuals become more empowered in their own lives, which promotes
      recovery. The study sought to determine the effectiveness of combined SHA and
      community mental health agency (CMHA) services in assisting recovery for persons
      with serious mental illness. METHODS: A weighted sample of new clients seeking
      CMHA services was randomly assigned to regular CMHA services or to combined SHA
      CMHA services at five proximally located pairs of SHA drop-in centers and county
      CMHAs. Member-clients (N=505) were assessed at baseline and at one, three, and
      eight months on five recovery-focused outcome measures: personal empowerment,
      self-efficacy, social integration, hope, and psychological functioning. Scales
      had high levels of reliability and independently established validity. Outcomes
      were evaluated with a repeated-measures multivariate analysis of covariance.
      RESULTS: Overall results indicated that combined SHA-CMHA services were
      significantly better able to promote recovery of client-members than CMHA
      services alone. The sample with combined services showed greater improvements in
      personal empowerment (F=3.99, df=3 and 491, p<.008), self-efficacy (F=11.20, df=3
      and 491, p<.001), and independent social integration (F=12.13, df=3 and 491,
      p<.001). Hopelessness (F=4.36, df=3 and 491, p<.005) and symptoms (F=4.49, df=3
      and 491, p<.004) dissipated more quickly and to a greater extent in the combined
      condition than in the CMHA-only condition. CONCLUSIONS: Member-empowering SHAs
      run as participatory democracies in combination with CMHA services produced more
      positive recovery-focused results than CMHA services alone.

PMID- 20810591
TI  - The role of religion in the well-being of older adults with schizophrenia.
AB  - OBJECTIVES: This study examined a community sample of older adults with
      schizophrenia to determine whether there were differences in religiousness with
      their age peers, to examine the relationship between religiousness and psychotic
      symptoms, and to see whether religiousness has direct or stress-buffering effects
      on quality of life. METHODS: The schizophrenia group consisted of 198 community
      dwelling persons aged 55 and older who developed schizophrenia before age 45.A
      community comparison group (N=113) was recruited using randomly selected block
      groups. A seven-item religiousness scale was developed that consisted of three
      dimensions (salience, coping, and attendance). An adaptation of Pearlin and
      colleagues' Stress Process Model was used to examine the direct and buffering
      effects of religiousness on quality of life. RESULTS: Persons with schizophrenia
      had significantly lower levels of religiousness than their age peers, although
      this was due to less frequent religious attendance (four times a year versus once
      a month). Religiousness was not significantly associated with psychotic symptoms,
      nor did it have any buffering effects on the relationship between psychosis and
      quality of life. Religiousness had a significant, albeit modest, independent
      additive effect on quality of life, and it did not have any buffering effects on
      the four stressors that were significantly associated with quality of life.
      CONCLUSIONS: Religiousness may have a favorable impact on the quality of life of
      older adults with schizophrenia, and it must be considered along with other
      therapeutically important agents.

PMID- 20810590
TI  - Perceived coercion among jail diversion participants in a multisite study.
AB  - OBJECTIVE: Although jail diversion is considered an appropriate and humane
      response to the disproportionately high volume of people with mental illness who
      are incarcerated, little is known regarding the perceptions of jail diversion
      participants, the extent to which they feel coerced into participating, and
      whether perceived coercion reduces involvement in mental health services. This
      study addressed perceived coercion among participants in postbooking jail
      diversion programs in a multisite study and examined characteristics associated
      with the perception of coercion. METHODS: Data collected in interviews with 905
      jail diversion participants from 2003 to 2005 were analyzed with random-effects
      proportional odds models. RESULTS: Ten percent of participants reported a high
      level of coercion, and another 26% reported a moderate level of coercion. Having
      a drug charge was associated with lower perceived coercion to enter the program.
      In addition, an interaction between sexual abuse and substance abuse indicated
      that recent sexual abuse was associated with higher levels of perceived coercion,
      but only among those without current substance abuse. At the 12-month follow-up
      (N=398), variables associated with higher perceived coercion to receive
      behavioral health services included spending more time in jail and higher
      perceived coercion at baseline. The amount of behavioral health service use was
      not predicted by perceived coercion at baseline. Rather, being older, having
      greater symptom severity, and having a history of sexual abuse but no substance
      abuse and no history of physical abuse were associated with higher levels of
      outpatient service use. CONCLUSIONS: Overall, one-third of jail diversion
      participants reported some level of perceived coercion. Important determinants of
      perceived coercion included charge type, length of time in jail, and sexual abuse
      history. Engagement in treatment was not affected by perceived coercion.

PMID- 20810592
TI  - Validation of brief screening tools for mental disorders among New Zealand
      prisoners.
AB  - OBJECTIVE: This study aimed to validate brief intake screens for serious mental
      illnesses among New Zealand male prisoners. METHODS: A prospective survey of
      consecutively admitted male remanded and sentenced prisoners was conducted across
      two New Zealand sites. Participants completed the Brief Jail Mental Health Screen
      (BJMHS) and the English Mental Health Screen (EMHS) upon prison admission. The
      validation standard, the Mini International Neuropsychiatric Interview (MINI),
      was completed for all positive screens and a random selection of negative
      screens. RESULTS: A total of 1,292 brief screens and 530 MINI screens were
      completed. Fifty-one percent of the participants met MINI criteria for one of
      five targeted major mental disorders. In this study, the BJMHS performed with
      lower sensitivity, higher specificity, a lower false-positive rate, a
      significantly higher false-negative rate, and a much higher referral rate than in
      the validating U.S. study. And in this study the EMHS performed with lower
      sensitivity, less specificity, higher false-positive and false-negative rates,
      and a moderately higher overall referral rate than in the validating U.K. study.
      For the BJMHS and EMHS, the majority of false-negative cases involved a mood
      disorder and few involved psychosis. CONCLUSIONS: Although the BJMHS and EMHS did
      not perform well in terms of screening for MINI diagnoses, they appeared to be
      good at identifying a core group of prisoners who are psychotic and most likely
      to require urgent or semi-urgent intervention by mental health services. The most
      favorable clinical outcomes were achieved by defining a positive screen as one in
      which either the EMHS or the BJMHS criteria were fulfilled.

PMID- 20810593
TI  - Staff and consumer perspectives on defining treatment success and failure in
      assertive community treatment.
AB  - OBJECTIVE: Although assertive community treatment (ACT) has been consistently
      recognized as effective, there has been little research as to what constitutes
      success in ACT. The purpose of this study was to understand how ACT consumers and
      staff define treatment success and failure and to examine whether definitions
      varied between staff and consumers. METHODS: Investigators conducted
      semistructured interviews with 25 staff and 23 consumers from four ACT teams.
      RESULTS: Across perspectives, success and failure were most clearly related to
      consumer factors. Other themes included having basic needs met, being socially
      involved, and taking medications. Reduced hospitalizations were mentioned
      infrequently. Consumers were more likely than staff to identify the level or type
      of treatment as defining success and failure, whereas staff were more likely than
      consumers to discuss substance abuse when defining failure and improved symptoms
      when defining success. CONCLUSIONS: Success in ACT should be viewed more broadly
      than reduced hospitalizations and include domains such as social involvement.

PMID- 20810594
TI  - Validating the empowerment scale with a multisite sample of consumers of mental
      health services.
AB  - OBJECTIVE: Empowerment is a key aspect of recovery and a common term in the
      mental health field, but there are few consistent definitions or validated
      measures of the construct. This study conducted psychometric testing on the
      Empowerment Scale, a widely used measure in the field. METHODS: As part of the
      Consumer-Operated Multi-Site study funded by the Substance Abuse and Mental
      Health Services Administration, consumers with a psychiatric disability were
      administered the Empowerment Scale along with several other scales to measure
      clinical status and psychosocial factors. RESULTS: Analyses produced five factors
      with acceptable fit statistics. The total scale demonstrated excellent
      reliability and validity. CONCLUSIONS: Analyses provide additional evidence that
      the total Empowerment Scale score is a reliable, valid measure; subscales of the
      scale appear less robust. Empowerment is considered an essential factor in
      recovery-oriented programs and systems, and the use of psychometrically sound
      measures such as the Empowerment Scale therefore may be useful to evaluators.

PMID- 20810595
TI  - Short-term impact of preferred drug list changes on health care use and Medicaid
      costs: injectable risperidone.
AB  - OBJECTIVE: This study assessed short-term effects of the removal of injectable
      risperidone long-acting therapy from the Florida Medicaid preferred drug list
      (PDL) in April 2006. METHODS: A difference-in-difference approach was used to
      contrast changes (60 days pre and post) in health care utilization and costs of
      Medicaid recipients who were receiving risperidone long-acting therapy when the
      policy was changed (N=247) and of a matched sample who received risperidone long
      acting therapy in April 2005 (non-PDL, N=247). RESULTS: The policy change was
      associated with increased acute care events. Whereas acute care events declined
      for the non-PDL group, involuntary commitments and total acute care events
      increased for the PDL group, as did expenditures for crisis-related events.
      Medicaid pharmacy costs fell for both groups, but total expenditures did not
      decline significantly for the PDL group. CONCLUSIONS: The PDL restriction was
      associated with increased acute care events and did not reduce short-term
      Medicaid program expenditures.

PMID- 20810596
TI  - Cognitive-behavioral therapy as an adjunct to second-generation antipsychotics in
      the treatment of schizophrenia.
AB  - OBJECTIVE: This study determined whether adding cognitive-behavioral therapy to
      treatment for outpatients with schizophrenia would be more effective than the use
      of second-generation antipsychotics alone. Thirty-three patients were randomly
      assigned to receive either second-generation antipsychotics alone (N=18) or
      second-generation antipsychotics plus cognitive-behavioral therapy (N=15).
      METHODS: All patients received pharmacotherapy from a single provider and in a
      predetermined standard manner. Psychopathology ratings were done at baseline, at
      the end of treatment (12 weeks) and three months after completion of treatment
      (24 weeks). RESULTS: Twenty-five (76%) patients completed baseline and 12-week
      evaluations, and 17 (68%) patients who finished treatment also completed
      evaluations at 24 weeks. At the end of treatment persons in the second-generation
      antipsychotics plus cognitive-behavioral therapy group were rated as having less
      severe delusions than patients in the group receiving second-generation
      antipsychotics only, and this difference was maintained three months after
      treatment ended. CONCLUSIONS: Adding cognitive-behavioral therapy may help with
      reducing the severity of delusions among patients with schizophrenia.

PMID- 20810597
TI  - Recovery Is Up to You, a peer-run course.

PMID- 20810598
TI  - Pathways to recovery, a peer-led group intervention.

PMID- 20810599
TI  - Sources of bias in guideline development.

PMID- 20810600
TI  - Screening for personality disorders among Chinese prison inmates.

PMID- 20810601
TI  - CoGAPS: an R/C++ package to identify patterns and biological process activity in
      transcriptomic data.
AB  - SUMMARY: Coordinated Gene Activity in Pattern Sets (CoGAPS) provides an
      integrated package for isolating gene expression driven by a biological process,
      enhancing inference of biological processes from transcriptomic data. CoGAPS
      improves on other enrichment measurement methods by combining a Markov chain
      Monte Carlo (MCMC) matrix factorization algorithm (GAPS) with a threshold
      independent statistic inferring activity on gene sets. The software is provided
      as open source C++ code built on top of JAGS software with an R interface.
      AVAILABILITY: The R package CoGAPS and the C++ package GAPS-JAGS are provided
      open source under the GNU Lesser Public License (GLPL) with a users manual
      containing installation and operating instructions. CoGAPS is available through
      Bioconductor and depends on the rjags package available through CRAN to interface
      CoGAPS with GAPS-JAGS. URL: http://www.cancerbiostats.onc.jhmi.edu/cogaps.cfm .

PMID- 20810602
TI  - Click-words: learning to predict document keywords from a user perspective.
AB  - MOTIVATION: Recognizing words that are key to a document is important for ranking
      relevant scientific documents. Traditionally, important words in a document are
      either nominated subjectively by authors and indexers or selected objectively by
      some statistical measures. As an alternative, we propose to use documents' words
      popularity in user queries to identify click-words, a set of prominent words from
      the users' perspective. Although they often overlap, click-words differ
      significantly from other document keywords. RESULTS: We developed a machine
      learning approach to learn the unique characteristics of click-words. Each word
      was represented by a set of features that included different types of
      information, such as semantic type, part of speech tag, term frequency-inverse
      document frequency (TF-IDF) weight and location in the abstract. We identified
      the most important features and evaluated our model using 6 months of PubMed
      click-through logs. Our results suggest that, in addition to carrying high TF-IDF
      weight, click-words tend to be biomedical entities, to exist in article titles,
      and to occur repeatedly in article abstracts. Given the abstract and title of a
      document, we are able to accurately predict the words likely to appear in user
      queries that lead to document clicks.

PMID- 20810603
TI  - Cost-effectiveness of colorectal cancer screening in high-risk Spanish patients:
      use of a validated model to inform public policy.
AB  - BACKGROUND: The European Community has made a commitment to colorectal cancer
      (CRC) screening, but regional considerations may affect the design of national
      screening programs. We developed a decision analytic model tailored to a pilot
      screening program for high-risk persons in Spain with the aim of informing public
      policy decisions. MATERIALS AND METHODS: We constructed a decision analytic
      Markov model based on our validated model of CRC screening that reflected CRC
      epidemiology and costs in persons with first-degree relatives with CRC in Aragon,
      Spain, and superimposed colonoscopy every 5 or 10 years from ages 40 to 80 years.
      The pilot program's preliminary clinical results and our modeling results were
      presented to regional health authorities. RESULTS: In the model, without
      screening, 88 CRC cases occurred per 1,000 persons from age 40 to 85 years. In
      the base case, screening reduced this by 72% to 77% and gained 0.12 discounted
      life years per person. Screening every 10 years was cost saving, and screening
      every 5 years versus every 10 years cost 7,250 euros per life year gained. Based
      on these savings, 36 to 39 euros per person per year could go toward operating
      costs while maintaining a neutral budget. If screening costs doubled, screening
      remained highly cost-effective but no longer cost saving. These results
      contributed to the health authorities' decision to expand the pilot program to
      the entire region in 2009. CONCLUSIONS: Colonoscopic screening of first-degree
      relatives of persons with CRC may be cost saving in public systems like that of
      Spain. Decision analytic modeling tailored to regional considerations can inform
      public policy decisions. IMPACT: Tailored decision analytic modeling can inform
      regional policy decisions on cancer screening.

PMID- 20810605
TI  - Detection of early-stage pancreatic adenocarcinoma.
AB  - BACKGROUND: Pancreatic adenocarcinoma is an almost universally lethal disease, in
      large part, due to our inability to detect early-stage disease. Monoclonal
      antibody PAM4 is reactive with a unique biomarker expressed by >85% of pancreatic
      adenocarcinomas. In this report, we examined the ability of a PAM4-based
      immunoassay to detect early-stage disease. MATERIALS AND METHODS: The PAM4-based
      immunoassay was used to quantitate antigen in the serum of healthy volunteers (n
      = 19), patients with known pancreatic adenocarcinoma (n = 68), and patients with
      a primary diagnosis of chronic pancreatitis (n = 29). RESULTS: Sensitivity for
      detection of pancreatic adenocarcinoma was 82%, with a false-positive rate of 5%
      for healthy controls. Patients with advanced disease had significantly higher
      antigen levels than those with early-stage disease (P < 0.01), with a diagnostic
      sensitivity of 91%, 86%, and 62% for stage 3/stage 4 advanced disease, stage 2,
      and stage 1, respectively. We also evaluated chronic pancreatitis sera, finding
      38% positive for antigen; however, this was discordant with immunohistochemical
      findings that suggest the PAM4 antigen is not produced by inflamed pancreatic
      tissue. Furthermore, several of the serum-positive pancreatitis patients, for
      whom tissue specimens were available for pathologic interpretation, had evidence
      of neoplastic precursor lesions. CONCLUSIONS: These results suggest the use of
      the PAM4 serum assay to detect early-stage pancreatic adenocarcinoma and that
      positive levels of PAM4 antigen are not derived from inflamed pancreatic tissues
      but rather may provide evidence of subclinical pancreatic neoplasia. EFFECT: The
      ability to detect pancreatic adenocarcinoma at an early stage could provide for
      early therapeutic intervention with potentially improved patient outcomes.

PMID- 20810604
TI  - Eighteen insulin-like growth factor pathway genes, circulating levels of IGF-I
      and its binding protein, and risk of prostate and breast cancer.
AB  - BACKGROUND: Circulating levels of insulin-like growth factor I (IGF-I) and its
      main binding protein, IGF binding protein 3 (IGFBP-3), have been associated with
      risk of several types of cancer. Heritable factors explain up to 60% of the
      variation in IGF-I and IGFBP-3 in studies of adult twins. METHODS: We
      systematically examined common genetic variation in 18 genes in the IGF signaling
      pathway for associations with circulating levels of IGF-I and IGFBP-3. A total of
      302 single nucleotide polymorphisms (SNP) were genotyped in >5,500 Caucasian men
      and 5,500 Caucasian women from the Breast and Prostate Cancer Cohort Consortium.
      RESULTS: After adjusting for multiple testing, SNPs in the IGF1 and SSTR5 genes
      were significantly associated with circulating IGF-I (P < 2.1 * 10(-4)); SNPs in
      the IGFBP3 and IGFALS genes were significantly associated with circulating IGFBP
      3. Multi-SNP models explained R(2) = 0.62% of the variation in circulating IGF-I
      and 3.9% of the variation in circulating IGFBP-3. We saw no significant
      association between these multi-SNP predictors of circulating IGF-I or IGFBP-3
      and risk of prostate or breast cancers. CONCLUSION: Common genetic variation in
      the IGF1 and SSTR5 genes seems to influence circulating IGF-I levels, and
      variation in IGFBP3 and IGFALS seems to influence circulating IGFBP-3. However,
      these variants explain only a small percentage of the variation in circulating
      IGF-I and IGFBP-3 in Caucasian men and women. IMPACT: Further studies are needed
      to explore contributions from other genetic factors such as rare variants in
      these genes and variation outside of these genes.

PMID- 20810606
TI  - A cereal-based evening meal rich in indigestible carbohydrates increases plasma
      butyrate the next morning.
AB  - Epidemiological studies have shown an inverse relation between a whole grain
      consumption and risk of type-2 diabetes and cardiovascular disease. One tentative
      mechanism relates to colonic metabolism of indigestible carbohydrates. In a
      previous study, we reported a positive relation between colonic fermentation and
      improved glucose tolerance. This work can be seen as an extension of that study,
      focusing on the tentative role of specific colonic metabolites, i.e. SCFA. Plasma
      concentrations of acetate, propionate, and butyrate were determined in the
      morning in healthy participants (5 women and 10 men, mean +/- SD: 25.9 +/- 3.2 y,
      BMI < 25) following 8 different cereal-based evening meals (50 g available
      starch) varying in content of indigestible carbohydrates. Each participant
      consumed all test meals in a random order on separate evenings. At a standardized
      breakfast following evening test meals, the postprandial glucose response
      (incremental area under the curve, 0-120 min) was inversely related to plasma
      butyrate (r = -0.26; P < 0.01) and acetate (r = -0.20; P < 0.05) concentrations.
      Evening meals composed of high-amylose barley kernels or high-beta-glucan barley
      kernels resulted in higher plasma butyrate concentrations the following morning
      compared with an evening meal with white wheat bread (P < 0.05). The results
      support the view that cereal products rich in indigestible carbohydrates may
      improve glucose tolerance through a mechanism involving colonic fermentation and
      generation of SCFA, where in particular butyric acid may be involved. This
      mechanism may be one explanation by which whole grain is protective against type
      2 diabetes and cardiovascular disease.

PMID- 20810607
TI  - Smoking behavior among low-income black adults: patterns and correlates of
      smoking trajectories.
AB  - INTRODUCTION: Limited research has focused on identifying smoking patterns and
      correlates of cigarette use among low-income Blacks. Identifying smoking patterns
      and correlates of use would assist health providers to develop more culturally
      sensitive interventions. METHODS: A semiparametric group-based trajectory
      modeling strategy was used to empirically identify patterns of cigarette use
      among 947 low-income Black adults (47% women) enrolled in a sexual risk reduction
      intervention at a sexually transmitted disease clinic. Patients' cigarette use
      was assessed 4 times over a 12-month period; correlates of cigarette use were
      examined. RESULTS: Six smoking trajectories were empirically identified:
      none/rare smokers (n = 536), decreasing light smokers (n = 69), increasing light
      smokers (n = 51), low light smokers (n = 112), upper light smokers (n = 142), and
      moderate smokers (n = 33). Smoking trajectories were predicted by alcohol use,
      prior substance use treatment, marijuana use, and other illegal drug use, but the
      patterns varied by trajectory. DISCUSSION: Results from this study show that
      Blacks' smoking patterns are associated with several risk factors. These findings
      suggest that development of prevention and cessation programs should be targeted
      to the specific needs of Blacks' smoking trajectories.

PMID- 20810608
TI  - The transcription factor HNF1alpha regulates expression of chloride-proton
      exchanger ClC-5 in the renal proximal tubule.
AB  - The Cl(-)/H(+) exchanger ClC-5 is essential for the endocytic activity of the
      proximal tubule cells and the tubular clearance of proteins filtered in the
      glomeruli. The mechanisms that regulate the expression of ClC-5 in general and
      its specific expression in the proximal tubule are unknown. In this study, we
      investigated the hypothesis that the hepatocyte nuclear transcription factor
      HNF1alpha, which is predominantly expressed in proximal tubule segments, may
      directly regulate the expression of ClC-5. In situ hybridization demonstrated
      that the expression of Clcn5 overlaps with that of Hnf1alpha in the developing
      kidney as well as in absorptive epithelia, including the digestive tract and yolk
      sac. Multiple binding sites for HNF1 were mapped in the 5'-regulatory sequences
      of the mouse and human Clcn5/CLCN5 genes. The transactivation of the Clcn5/CLCN5
      promoter by HNF1alpha was verified in vitro, and the binding of HNF1alpha to the
      Clcn5 promoter in vivo was confirmed by chromatin immunoprecipitation in mouse
      kidney. The expression of Clcn5 was reduced in the proximal tubule segments of
      HNF1alpha-null kidneys, and it was rescued upon transfection of HNF1alpha-null
      cells with wild-type but not with mutant HNF1alpha. These data demonstrate that
      HNF1alpha directly regulates the expression of ClC-5 in the renal proximal tubule
      and yield insights into the mechanisms governing epithelial differentiation and
      specialized transport activities in the kidney.

PMID- 20810609
TI  - Nuclear angiotensin-(1-7) receptor is functionally coupled to the formation of
      nitric oxide.
AB  - The kidney is an important target for the actions of the renin-angiotensin system
      (RAS) and this tissue contains a complete local RAS that expresses the bioactive
      peptides angiotensin II (ANG II) and Ang-(1-7). We find both angiotensin type 1
      (AT(1)R) and type 2 (AT(2)R) receptors expressed on renal nuclei that stimulate
      reactive oxygen species and nitric oxide (NO), respectively. Since Ang-(1-7) also
      exhibits actions within the kidney and the Ang-(1-7)/Mas receptor protein
      contains a nuclear localization sequence, we determined the expression of Ang-(1
      7) receptors in nuclei isolated from the kidneys of young adult sheep. Binding
      studies with (125)I-[Sar(1)Thr(8)]-ANG II revealed sites sensitive to the Ang-(1
      7) antagonist [d-Ala(7)]-Ang-(1-7) (DALA, A779), as well as to AT(2) and AT(1)
      antagonists. Incubation of Ang-(1-7) [10(-15) to 10(-9) M] with isolated cortical
      nuclei elicited a dose-dependent increase in the fluorescence of the NO indicator
      [4-amino-5-methylamino-2',7']-difluorofluorescein diacetate. The NO response to
      Ang-(1-7) was abolished by the NO inhibitor N-nitro-l-arginine methyl ester and
      DALA, but not the AT(1) antagonist losartan or the AT(2) blocker PD123319.
      Immunofluorescent studies utilizing the Ang-(1-7)/Mas receptor antibody revealed
      immunolabeling of the proximal tubules but not staining within the glomerulus in
      cortical sections of the sheep kidney. In the nuclear fraction of isolated
      proximal tubules, immunoblots revealed the precursor angiotensinogen and renin,
      as well as functional activity for ACE, ACE2, and neprilysin. We conclude that
      renal nuclei express Ang-(1-7)/Mas receptors that are functionally linked to NO
      formation. The marked sensitivity of the intracellular NO response to Ang-(1-7)
      implicates a functional role of the Ang-(1-7) axis within the nucleus. Moreover,
      evidence for the precursor and enzymatic components of the RAS within the nuclear
      compartment of the proximal tubules provides a potential pathway for the
      intracellular generation of Ang-(1-7).

PMID- 20810610
TI  - Characterization of mesonephric development and regeneration using transgenic
      zebrafish.
AB  - The zebrafish is a valuable vertebrate model for kidney research. The majority of
      previous studies focused on the zebrafish pronephros, which comprises only two
      nephrons and is structurally simpler than the mesonephros of adult fish and the
      metanephros of mammals. To evaluate the zebrafish system for more complex studies
      of kidney development and regeneration, we investigated the development and
      postinjury regeneration of the mesonephros in adult zebrafish. Utilizing two
      transgenic zebrafish lines (wt1b::GFP and pod::NTR-mCherry), we characterized the
      developmental stages of individual mesonephric nephrons and the temporal-spatial
      pattern of mesonephrogenesis. We found that mesonephrogenesis continues
      throughout the life of zebrafish, with a rapid growth phase during the juvenile
      period and a slower phase in adulthood such that the total nephron number of
      juvenile and adult fish linearly correlates with body mass. Following gentamicin
      induced renal injury, the zebrafish mesonephros can undergo de novo regeneration
      of mesonephric nephrons, a process known as neonephrogenesis. We found that wt1b
      expression was induced in individually dispersed cells in the mesonephric
      interstitium as early as 48 h following injury. These wt1b-expressing cells
      formed aggregates by 72-96 h following injury which proceeded to form nephrons.
      This suggests that wt1b may serve as an early marker of fated renal progenitor
      cells. The synchronous nature of regenerative neonephrogenesis suggests that this
      process may be useful for studies of nephron development.

PMID- 20810613
TI  - Acute ischemic injury to the renal microvasculature in human kidney
      transplantation.
AB  - Increased understanding of the pathophysiology of ischemic acute kidney injury in
      renal transplantation may lead to novel therapies that improve early graft
      function. Therefore, we studied the renal microcirculation in ischemically
      injured kidneys from donors after cardiac death (DCD) and in living donor kidneys
      with minimal ischemia. During transplant surgery, peritubular capillaries were
      visualized by sidestream darkfield imaging. Despite a profound reduction in
      creatinine clearance, total renovascular resistance of DCD kidneys was similar to
      that of living donor kidneys. In contrast, renal microvascular perfusion in the
      early reperfusion period was 42% lower in DCD kidneys compared with living donor
      kidneys, which was accounted for by smaller blood vessel diameters in DCD
      kidneys. Furthermore, DCD kidneys were characterized by smaller red blood cell
      exclusion zones in peritubular capillaries and by greater production of syndecan
      1 and heparan sulfate (main constituents of the endothelial glycocalyx) compared
      with living donor kidneys, providing strong evidence for glycocalyx degradation
      in these kidneys. We conclude that renal ischemia and reperfusion is associated
      with reduced capillary blood flow and loss of glycocalyx integrity. These
      findings form the basis for development of novel interventions to prevent
      ischemic acute kidney injury.

PMID- 20810611
TI  - Mechanotransduction in the renal tubule.
AB  - The role of mechanical forces in the regulation of glomerulotubular balance in
      the proximal tubule (PT) and Ca(2+) signaling in the distal nephron was first
      recognized a decade ago, when it was proposed that the microvilli in the PT and
      the primary cilium in the cortical collecting duct (CCD) acted as sensors of
      local tubular flow. In this review, we present a summary of the theoretical
      models and experiments that have been conducted to elucidate the structure and
      function of these unique apical structures in the modulation of Na(+), HCO(3)(-),
      and water reabsorption in the PT and Ca(2+) signaling in the CCD. We also
      contrast the mechanotransduction mechanisms in renal epithelium with those in
      other cells in which fluid shear stresses have been recognized to play a key role
      in initiating intracellular signaling, most notably endothelial cells, hair cells
      in the inner ear, and bone cells. In each case, small hydrodynamic forces need to
      be greatly amplified before they can be sensed by the cell's intracellular
      cytoskeleton to enable the cell to regulate its membrane transporters or stretch
      activated ion channels in maintaining homeostasis in response to changing flow
      conditions.

PMID- 20810612
TI  - Voltage-gated potassium channel Kv1.3 blocker as a potential treatment for rat
      anti-glomerular basement membrane glomerulonephritis.
AB  - The voltage-gated potassium channel Kv1.3 has been recently identified as a
      molecular target that allows the selective pharmacological suppression of
      effector memory T cells (T(EM)) without affecting the function of naive T cells
      (T(N)) and central memory T cells (T(CM)). We found that Kv1.3 was expressed on
      glomeruli and some tubules in rats with anti-glomerular basement membrane
      glomerulonephritis (anti-GBM GN). A flow cytometry analysis using kidney cells
      revealed that most of the CD4(+) T cells and some of the CD8(+) T cells had the
      T(EM) phenotype (CD45RC(-)CD62L(-)). Double immunofluorescence staining using
      mononuclear cell suspensions isolated from anti-GBM GN kidney showed that Kv1.3
      was expressed on T cells and some macrophages. We therefore investigated whether
      the Kv1.3 blocker Psora-4 can be used to treat anti-GBM GN. Rats that had been
      given an injection of rabbit anti-rat GBM antibody were also injected with Psora
      4 or the vehicle intraperitoneally. Rats given Psora-4 showed less proteinuria
      and fewer crescentic glomeruli than rats given the vehicle. These results suggest
      that T(EM) and some macrophages expressing Kv1.3 channels play a critical role in
      the pathogenesis of crescentic GN and that Psora-4 will be useful for the
      treatment of rapidly progressive glomerulonephritis.

PMID- 20810614
TI  - Reduction of renal dopamine receptor expression in obese Zucker rats: role of sex
      and angiotensin II.
AB  - Dopamine produced by renal proximal tubules increases sodium excretion via a
      decrease in renal sodium reabsorption. Dopamine natriuresis is impaired in obese
      Zucker rats; however, the mechanism is not fully understood. To test the
      hypothesis that renal expression of one or more of the subtypes are altered in
      these rats, we measured whole kidney protein levels by immunoblotting of D1-like
      (D1R and D5R) and D2-like (D2R, D3R, and D4R) dopamine receptors in both male and
      female obese and lean Zucker rats. In obese males on 1% NaCl diet, D1R, D2R, D4R,
      and D5R were decreased, while D3R was increased, relative to lean rats. Under a
      4% NaCl diet, D2R and D3R levels in obese rats were restored to lean levels. 4%
      NaCl diet reduced D5R in both body types, relative to 1% NaCl diet. Female rats
      had higher expression of D1R and D3R than did male; however, the sex difference
      for D1R was markedly blunted in obese rats. In obese rats, dietary candesartan
      (angiotensin II type 1 receptor blocker) normalized downregulated D1R and D2R,
      but either decreased (D3R), did not affect (D4R), or further downregulated (D5R)
      the other subtypes. Candesartan also decreased D4R in lean rats. In summary,
      reduced renal protein levels of D1R, D2R, D4R, and D5R in obese Zucker rats could
      induce salt sensitivity and elevate blood pressure. Increased angiotensin II type
      1 receptor activity may be mechanistically involved in the decreased expression
      of D1R and D2R in obese rats. Finally, reduced D1R and D3R in male rats may
      contribute to sex differences in blood pressure.

PMID- 20810615
TI  - Glomerular tubular balance is suppressed in adenosine type 1 receptor-deficient
      mice.
AB  - Glomerular tubular balance maintains a stable fractional solute and fluid
      reabsorption in the proximal tubule over a range of glomerular filtration rates.
      The mediators of this process are unknown. We tested the hypothesis that
      adenosine, produced in proximal tubule cells acting on adenosine type 1 receptors
      (A(1)-AR) promotes Na(+) and fluid uptake and mediates glomerular tubular
      balance. Absolute proximal fluid reabsorption (J(v)) was measured by in vivo
      microperfusion in A(1)-AR knockout and wild-type mice during perfusion of the
      closed proximal tubule at 2-10 nl/min. J(v) increased with perfusate flow from 2
      4 nl/min in both strains, but the fractional increase was lower in A(1)-AR(-/-)
      mice (A(1)-AR(+/+): 114% vs. A(1)-AR(-/-): 38%; P < 0.001), suggesting reduced
      glomerular tubular balance (GTB). At higher perfusion rates, J(v) increased
      modestly in both strains, indicating less GTB at higher flow. The physiological
      effects of reduced GTB in A(1)-AR(-/-) mice were assessed from the response to an
      acute volume load (1 ml/2 min). Na(+) excretion and urine flow increased 76 and
      73% more in A(1)-AR(-/-) mice than A(1)-AR(+/+) over the following 30 min,
      accompanied by a higher proximal tubule flow (A(1)-AR(-/-): 6.9 +/- 0.9 vs. A(1)
      AR(+/+): 5.2 +/- 0.6 nl/min; P < 0.05). The expression of the sodium-hydrogen
      exchanger 3 and sodium phosphate cotransporter-2 were similar between strains. In
      conclusion, GTB is dependent on adenosine acting on type 1 receptors in the
      proximal tubule. This may contribute to acute changes in Na(+) and fluid
      reabsorption.

PMID- 20810617
TI  - Targeting B-Raf as a treatment strategy for polycystic kidney disease.

PMID- 20810616
TI  - Sorafenib inhibits cAMP-dependent ERK activation, cell proliferation, and in
      vitro cyst growth of human ADPKD cyst epithelial cells.
AB  - In autosomal dominant polycystic kidney disease (ADPKD), aberrant proliferation
      of the renal epithelial cells is responsible for the formation of numerable fluid
      filled cysts, massively enlarged kidneys, and progressive loss of renal function.
      cAMP agonists, including arginine vasopressin, accelerate cyst epithelial cell
      proliferation through protein kinase A activation of the B-Raf/MEK/extracellular
      signal-regulated kinase (ERK) signaling pathway. The mitogenic effect of cAMP is
      equally potent and additive to growth factor stimulation. Here, we determined
      whether Sorafenib (BAY 43-9006), a small molecule Raf inhibitor, inhibits
      proliferation of cells derived from the cysts of human ADPKD kidneys. We found
      that nanomolar concentrations of Sorafenib reduced the basal activity of ERK,
      inhibited cAMP-dependent activation of B-Raf and MEK/ERK signaling, and caused a
      concentration-dependent inhibition of cell proliferation induced by cAMP,
      epidermal growth factor, or the combination of the two agonists. Sorafenib
      completely blocked in vitro cyst growth of human ADPKD cystic cells cultured
      within a three-dimensional collagen gel. These data demonstrate that cAMP
      dependent proliferation of human ADPKD cyst epithelial cells is blocked by
      Sorafenib and suggest that small molecule B-Raf inhibitors may be a therapeutic
      option to reduce the mitogenic effects of cAMP on cyst expansion.

PMID- 20810618
TI  - Identification and characterization of novel NMDA receptor antagonists selective
      for NR2A- over NR2B-containing receptors.
AB  - NR1/NR2A is a subtype of N-methyl-d-aspartate receptors (NMDARs), which are
      glutamate and glycine-gated Ca(2+)-permeable channels highly expressed in the
      central nervous system. A high-throughput screening (HTS) campaign using human
      osteosarcoma (U-2 OS) cells transiently transduced with NR1/NR2A NMDAR subunits,
      tested in a specifically designed fluorometric imaging plate reader
      (FLIPR)/Ca(2+) assay, identified sulfonamide derivative series, exemplified by 3
      chloro-4-fluoro-N-[(4-{[2
      (phenylcarbonyl)hydrazino]carbonyl}phenyl)methyl]benzenesulfonamide (compound 1)
      and thiodiazole derivative N-(cyclohexylmethyl)-2-({5-[(phenylmethyl)amino]-1,3,4
      thiadiazol-2-yl}thio)acetamide (compound 13) as novel NR1/NR2A receptor
      antagonists. Compounds 1 and 13 displayed submicromolar and micromolar potency at
      NR1/NR2A receptor, respectively, although they did not show activity at NR2B
      containing receptor up to 50 MUM concentration. Addition of 1 mM glycine, but not
      1 mM l-glutamate, was able to surmount compound 1 and 13 inhibitory effects in
      FLIPR NR1/NR2A assay. However, compounds 1 and 13 displaced a glutamate site
      antagonist [(3)H]d,l-(E)-2-amino-4-propyl-5-phosphono-3-pentenoic acid ([(3)H]CGP
      39653) to a greater extent than the glycine site antagonist [(3)H]3-[(E)-2
      carboxy-2-phenylethenyl]-4,6-dichloro-1H-indole-2-carboxylic acid ([(3)H]MDL
      105,519), in rat brain cortex binding assay. Results of FLIPR cell-based,
      electrophysiological, and biochemical binding assays suggest that compounds 1 and
      13 are the prototypes of novel classes of NMDAR ligands, which to the best of our
      knowledge are the first selective antagonists at NR1/NR2A over NR1/NR2B receptor,
      and might constitute useful tools able to elucidate the relative role of the NR2A
      subunit in physiological and pathological conditions.

PMID- 20810620
TI  - Recognition without awareness: an elusive phenomenon.
AB  - Two recent studies described conditions under which recognition memory
      performance appeared to be driven by nondeclarative memory. Specifically,
      participants successfully discriminated old images from highly similar new images
      even when no conscious memory for the images could be retrieved. Paradoxically,
      recognition performance was better when images were studied with divided
      attention than when images were studied with full attention. Furthermore,
      recognition performance was better when decisions were rated as guesses than when
      decisions were associated with low or high confidence. In three experiments, we
      adopted the paradigm used in the earlier studies in an attempt to repeat this
      intriguing work. Our attempts were unsuccessful. In all experiments, recognition
      was better when images were studied with full attention than when images were
      studied with divided attention. Recognition was also better when participants
      indicated high or low confidence in their decision than when they indicated that
      their decision was a guess. Thus, our results conformed to what typically has
      been reported in studies of recognition memory, and we were unable to demonstrate
      recognition without awareness. We encourage others to explore this paradigm, and
      to try to identify conditions under which the phenomenon might be demonstrated.

PMID- 20810619
TI  - Coupled RNA polymerase II transcription and 3' end formation with yeast whole
      cell extracts.
AB  - RNA polymerase II (RNAP II) transcription and pre-mRNA 3' end formation are
      linked through physical and functional interactions. We describe here a highly
      efficient yeast in vitro system that reproduces both transcription and 3' end
      formation in a single reaction. The system is based on simple whole-cell extracts
      that were supplemented with a hybrid Gal4-VP16 transcriptional activator and
      supercoiled plasmid DNA templates encoding G-less cassette reporters. We found
      that the coupling of transcription and processing in vitro enhanced pre-mRNA 3'
      end formation and reproduced requirements for poly(A) signals and polyadenylation
      factors. Unexpectedly, however, we show that in vitro transcripts lacked m7G
      caps. Reconstitution experiments with CF IA factor assembled entirely from
      heterologous components suggested that the CTD interaction domain of the Pcf11
      subunit was required for proper RNAP II termination but not 3' end formation.
      Moreover, we observed reduced termination activity associated with extracts
      prepared from cells carrying a mutation in the 5'-3' exonuclease Rat1 or
      following chemical inhibition of exonuclease activity. Thus, in vitro
      transcription coupled to pre-mRNA processing recapitulates hallmarks of poly(A)
      dependent RNAP II termination. The in vitro transcription/processing system
      presented here should provide a useful tool to further define the role of factors
      involved in coupling.

PMID- 20810622
TI  - The contributions of transient and sustained response codes to audiovisual
      integration.
AB  - Multisensory events in our natural environment unfold at multiple temporal scales
      over extended periods of time. This functional magnetic resonance imaging study
      investigated whether the brain uses transient (onset, offset) or sustained
      temporal codes to effectively integrate incoming visual and auditory signals
      within the cortical hierarchy. Subjects were presented with 1) velocity-modulated
      radial motion, 2) amplitude-modulated sound, or 3) an in phase combination of
      both in blocks of variable durations to dissociate transient and sustained blood
      oxygen level-dependent responses. Audiovisual interactions emerged primarily for
      transient onset and offset responses highlighting the importance of rapid
      stimulus transitions for multisensory integration. Strikingly, audiovisual
      interactions for onset and offset transients were dissociable at the functional
      and anatomical level. Low-level sensory areas integrated audiovisual inputs at
      stimulus onset in a superadditive fashion to enhance stimulus salience. In
      contrast, higher order association areas showed subadditive integration profiles
      at stimulus offset possibly reflecting the formation of higher order
      representations. In conclusion, multisensory integration emerges at multiple
      levels of the cortical hierarchy using different temporal codes and integration
      profiles. From a methodological perspective, these results highlight the
      limitations of conventional event related or block designs that cannot
      characterize these rich dynamics of audiovisual integration.

PMID- 20810621
TI  - What makes recognition without awareness appear to be elusive? Strategic factors
      that influence the accuracy of guesses.
AB  - Various factors could conceivably promote the accuracy of guesses during a
      recognition test. Two that we identified in previous studies are forced-choice
      testing format and high perceptual similarity between the repeat target and novel
      foil. In restricted circumstances, the relative perceptual fluency of the target
      can be compared with that of the foil and used as a reliable cue to guide
      accurate responses that occur without explicit retrieval--a phenomenon we
      referred to as "implicit recognition." In this issue, Jeneson and colleagues
      report a failure to replicate accurate guesses and also a tendency on the part of
      subjects to hazard guesses infrequently, even though testing circumstances were
      very similar to those that we used. To resolve this discrepancy, we developed a
      simple manipulation to encourage either guessing or confident responding.
      Encouraging guessing increased both the prevalence of guesses and the accuracy of
      guesses in a recognition test, relative to when confident responding was
      encouraged. When guessing was encouraged, guesses were highly accurate (as in our
      previous demonstrations of implicit recognition), whereas when confident
      responding was encouraged, guesses were at chance levels (as in Jeneson and
      colleagues' data). In light of a substantial literature showing high accuracy
      despite low confidence in certain circumstances, we infer that both the
      prevalence and accuracy of guessing can be influenced by whether subjects adopt
      guessing-friendly strategies. Our findings thus help to further characterize
      conditions likely to promote implicit recognition based on perceptual fluency.

PMID- 20810624
TI  - Equipment setup for Drosophila electrophysiology.
AB  - The Drosophila larval neuromuscular junction (NMJ) shares many structural and
      functional similarities to synapses in other animals, including humans. These
      include the basic feature of synaptic transmission, as well as the molecular
      mechanisms regulating the synaptic vesicle cycle. Because of its large size, easy
      accessibility, and the well-characterized genetics, the fly NMJ remains an
      excellent model system for dissecting the cellular and molecular mechanisms of
      synaptic transmission. This article describes the components of an
      electrophysiology setup, commonly referred to as an electrophysiology rig. The
      rig described here is based on equipment and software used in the Cold Spring
      Harbor Laboratory (CSHL) course "Neurobiology of Drosophila."

PMID- 20810625
TI  - Agarose imprints of plant cell surfaces for imaging.
AB  - Features of epidermal cells such as cell shape or arrangement of stomata are best
      studied under the scanning electron microscope. However, the preparation and
      viewing of samples using electron microscopy can be relatively laborious. A quick
      alternative is to view epidermal imprints in agarose using Nomarski differential
      interference contrast microscopy. This protocol describes a method for preparing
      agarose imprints of plant cell surfaces.

PMID- 20810623
TI  - Parental education predicts corticostriatal functionality in adulthood.
AB  - Socioeconomic disadvantage experienced in early development predicts ill health
      in adulthood. However, the neurobiological pathways linking early disadvantage to
      adult health remain unclear. Lower parental education-a presumptive indicator of
      early socioeconomic disadvantage-predicts health-impairing adult behaviors,
      including tobacco and alcohol dependencies. These behaviors depend, in part, on
      the functionality of corticostriatal brain systems that 1) show developmental
      plasticity and early vulnerability, 2) process reward-related information, and 3)
      regulate impulsive decisions and actions. Hence, corticostriatal functionality in
      adulthood may covary directly with indicators of early socioeconomic
      disadvantage, particularly lower parental education. Here, we tested the
      covariation between parental education and corticostriatal activation and
      connectivity in 76 adults without confounding clinical syndromes. Corticostriatal
      activation and connectivity were assessed during the processing of stimuli
      signaling monetary gains (positive feedback [PF]) and losses (negative feedback).
      After accounting for participants' own education and other explanatory factors,
      lower parental education predicted reduced activation in anterior cingulate and
      dorsomedial prefrontal cortices during PF, along with reduced connectivity
      between these cortices and orbitofrontal and striatal areas implicated in reward
      processing and impulse regulation. In speculation, adult alterations in
      corticostriatal functionality may represent facets of a neurobiological
      endophenotype linked to socioeconomic conditions of early development.

PMID- 20810626
TI  - Dental wax impressions of plant tissues for viewing with scanning electron
      microscopy (SEM).
AB  - Scanning electron microscopy (SEM) is a valuable method for examining surface
      structures. Taking wax impressions of plant structures, such as leaves, is a
      nondestructive procedure that makes it possible to view changes in surface
      structures over time, such as during development. This protocol describes a
      method for making dental wax impressions of plant tissues.

PMID- 20810627
TI  - Labeling the endoplasmic reticulum with DiO-C6(3) for imaging.
AB  - The eukaryotic cell has evolved to compartmentalize its functions and transport
      various metabolites among cellular compartments. Therefore, in cell biology, the
      study of organization and structure/function relationships are of great
      importance. The endoplasmic reticulum is a highly convoluted, single membrane
      that is continuous with the outer nuclear membrane and is believed to form a
      contiguous closed sac within the cell cytosol. Although a probe specific for the
      endoplasmic reticulum currently does not exist, the DiO-C(6)(3) probe, a cationic
      dye, is an effective label because of the distinctive intracellular morphology of
      the endoplasmic reticulum that distinguishes it from other intracellular
      organelles. This protocol describes the labeling of the endoplasmic reticulum
      with DiO-C(6)(3).

PMID- 20810628
TI  - Generation of stable cell lines expressing GFP-tubulin and photoactivatable-GFP
      tubulin and characterization of clones.
AB  - A bicistronic expression vector can be used to generate stable cell lines
      expressing green fluorescent protein (GFP)-tubulin and photoactivatable (PA)-GFP
      tubulin. This vector, pIRES (originally available from BD Biosciences/Clontech),
      expresses the gene of interest (GFP-tubulin) and a selection marker from the same
      promoter. The vector uses an internal ribosome entry site (IRES) derived from the
      encephalomyocarditis virus and translates two open-reading frames from one mRNA.
      The gene of interest is inserted immediately downstream from the pCMV IE
      promoter, and the selection marker is downstream from the IRES site. Selection is
      more efficient using this vector system, presumably because of the linked
      expression of both genes. IRES vectors have been used with neomycin- and
      hygromycin-resistance markers. Cell lines can also be generated for proteins
      cloned into standard vectors (i.e., pCMV).

PMID- 20810629
TI  - Production of foamy virus vector and transduction of hematopoietic cells.
AB  - Foamy viruses (FVs), or spumaviruses, are nonpathogenic retroviruses that have
      been developed as integrating viral vectors. This protocol presents methods for
      producing high-titer FV vector stocks, free of contaminating replication
      competent retrovirus, to be used for transducing hematopoietic stem cells. FV
      vector stocks are produced by transfecting 293 cells, harvesting and filtering
      the culture medium, and concentrating vector virions by ultracentrifugation. The
      resulting stocks are free of replication-competent helper virus, as indicated by
      a sensitive marker rescue assay. A typical stock made from 23 10-cm dishes has a
      final volume of 2 mL with a titer of 10(7) to 10(8) transducing units/mL.
      Potential advantages of FV vectors include a lack of pathogenicity of the wild
      type virus, a wide host range, stable virions that can be concentrated by
      centrifugation, a double-stranded DNA genome that is reverse-transcribed in the
      vector-producing cells, and the largest packaging capacity of any retrovirus. FV
      vectors are especially useful for transducing hematopoietic cells. Because
      hematopoietic stem cells have the ability to self-renew, proliferate, and
      repopulate the bone marrow after transplantation, efficient transduction of these
      cells offers the promise to cure many inherited and acquired diseases.

PMID- 20810630
TI  - Small-scale extraction of recombinant proteins from bacteria.
AB  - Bacteria are particularly convenient for producing recombinant proteins for
      purification purposes. To monitor induction as well as the levels of recombinant
      protein expression, it is important to have a rapid, simple method for estimating
      bacterial protein expression. This protocol describes the preparation of small
      scale bacterial extracts using cell lysis with 0.5% Triton X-100.

PMID- 20810631
TI  - Large-scale extraction of recombinant proteins from bacteria.
AB  - Bacteria are particularly convenient for producing recombinant proteins for
      purification purposes. Suitable extraction methods for bacterial cells include
      sonication, glass bead milling, grinding with alumina or sand, high-pressure
      shearing using the French pressure cell (French Press), and lysozyme treatment.
      These procedures are applicable for preparing extracts from a variety of gram
      negative bacteria such as Escherichia coli and Klebsiella pneumoniae, and gram
      positive bacteria such as Bacillus subtilis. Disruption of bacterial cells by
      enzymatic means is commonly used because a relatively uniform treatment is
      obtained when cells are in suspension. This protocol describes the enzymatic
      disruption of E. coli.

PMID- 20810632
TI  - Solubilization of Escherichia coli recombinant proteins from inclusion bodies.
AB  - The high levels of expression produced by molecular cloning techniques make
      bacteria particularly useful for producing recombinant proteins. However, these
      proteins often are difficult to purify, owing to their tendency to aggregate and
      precipitate within the bacteria as insoluble inclusion bodies. Formation of
      inclusion bodies is especially common for nonbacterial proteins. Although no
      single method can be applied to every protein, a number of strategies are
      available to solubilize inclusion body proteins. This protocol describes one such
      method.

PMID- 20810633
TI  - Electrophysiological recording from a 'model' cell.
AB  - The Drosophila larval neuromuscular junction (NMJ) shares many structural and
      functional similarities to synapses in other animals, including humans. These
      include the basic feature of synaptic transmission, as well as the molecular
      mechanisms regulating the synaptic vesicle cycle. Because of its large size, easy
      accessibility, and the well-characterized genetics, the fly NMJ remains an
      excellent model system for dissecting the cellular and molecular mechanisms of
      synaptic transmission. This protocol describes the basics of setting up and
      conducting electrophysiological experiments using a model cell. For the novice, a
      model cell provides a way to learn the operation of electrophysiology equipment
      and software without the anxiety of damaging living cells. This protocol also
      illustrates passive membrane properties such as the input resistance,
      capacitance, and time constant.

PMID- 20810634
TI  - Electrophysiological recording from Drosophila larval body-wall muscles.
AB  - The Drosophila larval neuromuscular junction (NMJ) shares many structural and
      functional similarities to synapses in other animals, including humans. These
      include the basic feature of synaptic transmission, as well as the molecular
      mechanisms regulating the synaptic vesicle cycle. Because of its large size, easy
      accessibility, and the well-characterized genetics, the fly NMJ remains an
      excellent model system for dissecting the cellular and molecular mechanisms of
      synaptic transmission. This protocol describes the steps for performing
      intracellular recording from fly larval body-wall muscles and explains how to
      record and analyze spontaneous and evoked synaptic potentials. Methods used
      include larval dissection ("filleting"), identification of muscle fibers and
      their innervating nerves, the use of a micromanipulator and microelectrode in
      penetrating the muscle membrane, and nerve stimulation to evoke synaptic
      potentials.

PMID- 20810635
TI  - Voltage-clamp analysis of synaptic transmission at the Drosophila larval
      neuromuscular junction.
AB  - The Drosophila larval neuromuscular junction (NMJ) shares many structural and
      functional similarities to synapses in other animals, including humans. These
      include the basic feature of synaptic transmission as well as the molecular
      mechanisms regulating the synaptic vesicle cycle. Because of its large size, easy
      accessibility, and the well-characterized genetics, the fly NMJ remains an
      excellent model system for dissecting the cellular and molecular mechanisms of
      synaptic transmission. Although intracellular recording is particularly valuable
      in revealing membrane potential changes, it has several limitations. Primarily,
      it does not offer information on the kinetics of membrane currents associated
      with ion channels or synaptic receptors responsible for the potential change.
      Furthermore, the resting potential of the Drosophila body-wall muscle varies
      naturally such that the driving force also varies considerably, making it
      difficult to accurately compare the amplitude of minis (spontaneous miniature
      synaptic potentials) or evoked excitatory junction potentials (EJPs). Finally,
      accurate determination of quantal content based on minis and EJPs is possible
      only at low release conditions when nonlinear summation is not a major issue. The
      voltage-clamp technique can overcome these limitations by using negative feedback
      mechanisms to keep the cell membrane potential steady at any reasonable set
      points. In the large larval muscle cells of Drosophila, the two-electrode voltage
      clamp (TEVC) method is used, in which one electrode monitors the cell membrane
      potential while the other electrode passes electric currents. This protocol
      introduces the application of TEVC in analysis of synaptic currents using the
      larval NMJ preparation.

PMID- 20810636
TI  - Focal recording of synaptic currents from single boutons at the Drosophila
      neuromuscular junction.
AB  - The Drosophila larval neuromuscular junction (NMJ) shares many structural and
      functional similarities to synapses in other animals, including humans. These
      include the basic feature of synaptic transmission, as well as the molecular
      mechanisms regulating the synaptic vesicle cycle. Because of its large size, easy
      accessibility, and the well-characterized genetics, the fly NMJ remains an
      excellent model system for dissecting the cellular and molecular mechanisms of
      synaptic transmission. Focal recording is an extracellular method designed for
      the study of synaptic activity of one or a few synaptic boutons rather than the
      ensemble activity of all of the boutons, as occurs with intracellular recording
      or the two-electrode voltage-clamp (TEVC) method. This is a useful technique for
      investigating the properties of different motor neurons that innervate the same
      muscle, applying statistical analysis to discrete synaptic events, and
      investigating the heterogeneity of synaptic release properties among boutons.

PMID- 20810637
TI  - Fabrication of microelectrodes, suction electrodes, and focal electrodes.
AB  - The Drosophila larval neuromuscular junction (NMJ) shares many structural and
      functional similarities to synapses in other animals, including humans. These
      include the basic feature of synaptic transmission, as well as the molecular
      mechanisms regulating the synaptic vesicle cycle. Because of its large size, easy
      accessibility, and well-characterized genetics, the fly NMJ remains an excellent
      model system for dissecting the cellular and molecular mechanisms of synaptic
      transmission. This protocol details some basic methods for manufacturing
      microelectrodes used for intracellular recording and two-electrode voltage-clamp
      (TEVC), and loose patch electrodes used for focal recording. In addition, a
      method is provided for manufacturing homemade suction electrodes used for nerve
      stimulation.

PMID- 20810638
TI  - Simple copy number determination with reference query pyrosequencing (RQPS).
AB  - The accurate measurement of the copy number (CN) for an allele is often desired.
      We have developed a simple pyrosequencing-based method, reference query
      pyrosequencing (RQPS), to determine the CN of any allele in any genome by taking
      advantage of the fact that pyrosequencing can accurately measure the molar ratio
      of DNA fragments in a mixture that differ by a single nucleotide. The method
      involves the preparation of an RQPS probe, which contains two linked DNA
      fragments that match a reference allele with a known CN and a query allele with
      an unknown CN. In each fragment, a single nucleotide variation (SNV) is
      engineered to differentiate it from its genomic counterparts when the probe is
      mixed with genomic DNA. The ratios of the two pairs of fragments (probe reference
      vs. genomic reference and probe query vs. genomic query) in the mixture reflect
      the ratio between the probe and the genomic DNA in a CN-dependent manner.
      Pyrosequencing can be used to quantify these ratios and thus determine the CN of
      the query allele. This method could be used to measure the CN of any transgene,
      differentiate homozygotes from heterozygotes, detect the copy number variation
      (CNV) of endogenous genes, and screen embryonic stem (ES) cells targeted with
      bacterial artificial chromosome (BAC) vectors that are not compatible with
      standard screening methods.

PMID- 20810639
TI  - Determination of gross chromosomal rearrangement rates.
AB  - Cells devote a significant amount of metabolism to maintaining the stability of
      their genome and to preventing inappropriate chromosomal rearrangements that are
      characteristic of many cancers. A simple genetic assay using haploid derivatives
      of the yeast Saccharomyces cerevisiae provides a means to quantitatively measure
      the rate at which gross chromosomal rearrangements (GCRs) accumulate in different
      genetic backgrounds. This assay measures the rate of simultaneous inactivation of
      CAN1 and URA3 markers placed on a nonessential end of a yeast chromosome and in
      principle can be implemented in any haploid strain. Rearrangements detected with
      this assay include broken chromosomes healed by de novo telomere additions and a
      spectrum of inter- and intrachromosomal fusion events. The GCR assay allows for
      detailed analysis of the contributions of individual genes and different pathways
      in the suppression of genomic instability.

PMID- 20810640
TI  - Fluorescence in situ hybridization of bacterial cell suspensions.
AB  - The use of fluorescence in situ hybridization (FISH) to identify and enumerate
      specific bacteria within a mixed culture or environmental sample has become a
      powerful tool in combining microscopy with molecular phylogenetic discrimination.
      However, processing a large number of samples in parallel can be difficult
      because the bacterial cells are typically fixed and hybridized on microscope
      slides rather than processed in solution. In addition, gram-positive cells and
      certain environmental samples present a unique challenge to achievement of
      adequate cell fixation and uniform hybridization for optimal FISH analysis. Here,
      we describe a protocol for FISH in solution that can be performed entirely in
      suspension, in a microcentrifuge tube format, prior to microscopy. This protocol
      can be applied to both gram-positive and -negative cells, as well as complex
      microbial assemblages. The method employs a rapid technique for performing
      multiple hybridizations simultaneously, which may be used to qualitatively assess
      the presence of specific phylogenetic groups in bacterial cultures or
      environmental samples, and/or directly quantify fluorescence by fluorometry or
      flow cytometry.

PMID- 20810641
TI  - Two-photon fluorescence microscopy of cerebral hemodynamics.
AB  - Under physiological conditions, neuronal activity is tightly coupled to
      hemodynamics of the surrounding microvessels. Conversely, most brain diseases are
      associated with a disturbance in neurovascular coupling. Measuring the
      hemodynamic response of the microvascular network to neuronal stimulation in vivo
      involves two major challenges: maintaining a stable systemic physiological state
      in the animal and imaging with sufficient temporal and spatial resolution to
      capture the hemodynamic changes across the three-dimensional cortical
      microvascular network. Two-photon fluorescence microscopy allows imaging of
      intact cortex in situ at micrometer spatial and microsecond temporal resolution.
      However, this modality necessitates focal opening of the skull because of its
      high scattering of light waves. This protocol describes in detail the requisite
      surgical preparation and physiological maintenance of an adolescent rat with a
      closed cranial window. Two-photon fluorescence laser scanning microscopy is then
      used to image the hemodynamic response of the microvasculature of the primary
      somatosensory cortex to electrical stimulation of the forepaw, with the end goal
      of quantitative analysis of brain hemodynamics.

PMID- 20810642
TI  - In vivo imaging of cerebral hemodynamics using high-frequency micro-ultrasound.
AB  - Assessment of cerebral vascular response is important in neuroscience research.
      Some imaging modalities that are commonly used to detect flow and/or vessel
      diameter changes in the brain include magnetic resonance imaging, positron
      emission tomography, and optical intrinsic signal imaging. Ultrasound has not
      typically been used to assess neurovascular response but recent advances in the
      technology have led to the development of micro-ultrasound systems with
      significant potential for this application. The state of the art in high
      frequency (15-50 MHz) micro-ultrasound is based on linear arrays specifically
      designed for small animal imaging. These systems can achieve axial resolution
      ranging from 30 to 200 microm. They are capable of quantifying brain hemodynamics
      in terms of red blood cell (RBC) velocity, flow, and vascular density in real
      time, up to 35 mm below the cortical surface, and can achieve temporal resolution
      of up to 1000 frames per second. This protocol describes imaging of the rat brain
      using various ultrasound imaging modes (power Doppler, color Doppler, pulsed-wave
      Doppler, and nonlinear contrast-enhanced imaging) to assess the state of cerebral
      microcirculation.

PMID- 20810643
TI  - Methods for expressing and analyzing GFP-tubulin and GFP-microtubule-associated
      proteins.
AB  - Important advances in our understanding of the organization and dynamics of the
      cytoskeleton have been made by direct observations of fluorescently tagged
      cytoskeletal proteins in living cells. In early experiments, the cytoskeletal
      protein of interest was purified, covalently modified with a fluorescent dye, and
      microinjected into living cells. In the mid-1990s, a powerful new technology
      arose: Researchers developed methods for expressing chimeric proteins consisting
      of the gene of interest fused to green fluorescent protein (GFP). This approach
      has become a standard method for characterizing protein localization and
      dynamics. More recently, a profusion of "XFP" (spectral variants of GFP) has been
      developed, allowing researchers straightforwardly to perform experiments ranging
      from simultaneous co-observation of protein dynamics to fluorescence recovery
      after photobleaching (FRAP), fluorescence resonance energy transfer (FRET), and
      subresolution techniques such as stimulated emission-depletion microscopy (STED)
      and photoactivated localization microscopy (PALM). In this article, the methods
      used to express and analyze GFP- and/or XFP-tagged tubulin and microtubule
      associated proteins (MAPs) are discussed. Although some details may be system
      specific, the methods and considerations outlined here can be adapted to a wide
      variety of proteins and organisms.

PMID- 20810644
TI  - The cytoplasmic fate of an mRNP is determined cotranscriptionally: exception or
      rule?
AB  - She2p is an RNA-binding protein that recognizes a zipcode on specific mRNAs
      necessary for the assembly of a protein complex that localizes them to the yeast
      bud tip. In this issue of Genes & Development, Shen and colleagues (pp. 1914
      1926) demonstrate that She2p associates with RNAPII globally, but then recognizes
      the nascent chain only if it contains a zipcode. This demonstrates yet another
      case where the mRNA's cytoplasmic fate is determined by the RNAPII complex.

PMID- 20810646
TI  - Classic and contemporary approaches to modeling biochemical reactions.
AB  - Recent interest in modeling biochemical networks raises questions about the
      relationship between often complex mathematical models and familiar arithmetic
      concepts from classical enzymology, and also about connections between modeling
      and experimental data. This review addresses both topics by familiarizing readers
      with key concepts (and terminology) in the construction, validation, and
      application of deterministic biochemical models, with particular emphasis on a
      simple enzyme-catalyzed reaction. Networks of coupled ordinary differential
      equations (ODEs) are the natural language for describing enzyme kinetics in a
      mass action approximation. We illustrate this point by showing how the familiar
      Briggs-Haldane formulation of Michaelis-Menten kinetics derives from the outer
      (or quasi-steady-state) solution of a dynamical system of ODEs describing a
      simple reaction under special conditions. We discuss how parameters in the
      Michaelis-Menten approximation and in the underlying ODE network can be estimated
      from experimental data, with a special emphasis on the origins of uncertainty.
      Finally, we extrapolate from a simple reaction to complex models of multiprotein
      biochemical networks. The concepts described in this review, hitherto of interest
      primarily to practitioners, are likely to become important for a much broader
      community of cellular and molecular biologists attempting to understand the
      promise and challenges of "systems biology" as applied to biochemical mechanisms.

PMID- 20810647
TI  - s-SHIP promoter expression marks activated stem cells in developing mouse mammary
      tissue.
AB  - Mammary stem cells (MaSCs) play critical roles in normal development and perhaps
      tumorigenesis of the mammary gland. Using combined cell markers, adult MaSCs have
      been enriched in a basal cell population, but the exact identity of MaSCs remains
      unknown. We used the s-SHIP promoter to tag presumptive stem cells with GFP in
      the embryos of a transgenic mouse model. Here we show, in postnatal mammary gland
      development, that GFP(+) cap cells in puberty and basal alveolar bud cells in
      pregnancy each exhibit self-renewal and regenerative capabilities for all mammary
      epithelial cells of a new functional mammary gland upon transplantation. Single
      GFP(+) cells can regenerate the mammary epithelial network. GFP(+) mammary
      epithelial cells are p63(+), CD24(mod), CD49f(high), and CD29(high); are actively
      proliferating; and express s-SHIP mRNA. Overall, our results identify the
      activated MaSC population in vivo at the forefront of rapidly developing terminal
      end buds (puberty) and alveolar buds (pregnancy) in the mammary gland. In
      addition, GFP(+) basal cells are expanded in MMTV-Wnt1 breast tumors but not in
      ErbB2 tumors. These results enable MaSC in situ identification and isolation via
      a consistent single parameter using a new mouse model with applications for
      further analyses of normal and potential cancer stem cells.

PMID- 20810648
TI  - Homocitrate synthase connects amino acid metabolism to chromatin functions
      through Esa1 and DNA damage.
AB  - The enzyme homocitrate synthase (HCS) catalyzes the first step in lysine
      biosynthesis, and early biochemical data placed it in the cytoplasm or
      mitochondria, where most amino acid synthesis occurs. It was therefore surprising
      when refined fractionation techniques and specific immunoreagents clearly
      demonstrated its localization to the nucleus. These observations raised the
      question of whether HCS had a function within the nucleus independent of lysine
      synthesis. We demonstrate that HCS encoded by LYS20 in yeast is linked to the key
      process of DNA damage repair through the essential MYST family histone
      acetyltransferase Esa1 and the H2A.Z histone variant. This discovery indicates
      that HCS has a role in addition to amino acid synthesis, and that it functions in
      nuclear activities involving chromatin regulation that are distinct from its
      previously established role in lysine biosynthesis. The chromatin-linked roles
      are dependent on nuclear localization of Lys20, but are independent of HCS
      catalytic activity. Thus, Lys20 appears to have evolved as a bifunctional protein
      that connects cellular metabolism with chromatin functions.

PMID- 20810649
TI  - Ubiquitin-mediated mRNP dynamics and surveillance prior to budding yeast mRNA
      export.
AB  - The evolutionarily conserved mRNA export receptor Mex67/NXF1 associates with
      mRNAs through its adaptor, Yra1/REF, allowing mRNA ribonucleoprotein (mRNP) exit
      through nuclear pores. However, alternate adaptors should exist, since Yra1 is
      dispensable for mRNA export in Drosophila and Caenorhabditis elegans. Here we
      report that Mex67 interacts directly with Nab2, an essential shuttling mRNA
      binding protein required for export. We further show that Yra1 enhances the
      interaction between Nab2 and Mex67, and becomes dispensable in cells
      overexpressing Nab2 or Mex67. These observations appoint Nab2 as a potential
      adaptor for Mex67, and define Yra1/REF as a cofactor stabilizing the adaptor
      receptor interaction. Importantly, Yra1 ubiquitination by the E3 ligase Tom1
      promotes its dissociation from mRNP before export. Finally, loss of perinuclear
      Mlp proteins suppresses the growth defects of Tom1 and Yra1 ubiquitination
      mutants, suggesting that Tom1-mediated dissociation of Yra1 from Nab2-bound mRNAs
      is part of a surveillance mechanism at the pore, ensuring export of mature mRNPs
      only.

PMID- 20810645
TI  - tRNA biology charges to the front.
AB  - tRNA biology has come of age, revealing an unprecedented level of understanding
      and many unexpected discoveries along the way. This review highlights new
      findings on the diverse pathways of tRNA maturation, and on the formation and
      function of a number of modifications. Topics of special focus include the
      regulation of tRNA biosynthesis, quality control tRNA turnover mechanisms,
      widespread tRNA cleavage pathways activated in response to stress and other
      growth conditions, emerging evidence of signaling pathways involving tRNA and
      cleavage fragments, and the sophisticated intracellular tRNA trafficking that
      occurs during and after biosynthesis.

PMID- 20810650
TI  - A genetic screen identifies the Triple T complex required for DNA damage
      signaling and ATM and ATR stability.
AB  - In response to DNA damage, cells activate a complex signal transduction network
      called the DNA damage response (DDR). To enhance our current understanding of the
      DDR network, we performed a genome-wide RNAi screen to identify genes required
      for resistance to ionizing radiation (IR). Along with a number of known DDR
      genes, we discovered a large set of novel genes whose depletion leads to cellular
      sensitivity to IR. Here we describe TTI1 (Tel two-interacting protein 1) and TTI2
      as highly conserved regulators of the DDR in mammals. TTI1 and TTI2 protect cells
      from spontaneous DNA damage, and are required for the establishment of the intra
      S and G2/M checkpoints. TTI1 and TTI2 exist in multiple complexes, including a 2
      MDa complex with TEL2 (telomere maintenance 2), called the Triple T complex, and
      phosphoinositide-3-kinase-related protein kinases (PIKKs) such as ataxia
      telangiectasia-mutated (ATM). The components of the TTT complex are mutually
      dependent on each other, and act as critical regulators of PIKK abundance and
      checkpoint signaling.

PMID- 20810651
TI  - Human sodium phosphate transporter 4 (hNPT4/SLC17A3) as a common renal secretory
      pathway for drugs and urate.
AB  - The evolutionary loss of hepatic urate oxidase (uricase) has resulted in humans
      with elevated serum uric acid (urate). Uricase loss may have been beneficial to
      early primate survival. However, an elevated serum urate has predisposed man to
      hyperuricemia, a metabolic disturbance leading to gout, hypertension, and various
      cardiovascular diseases. Human serum urate levels are largely determined by urate
      reabsorption and secretion in the kidney. Renal urate reabsorption is controlled
      via two proximal tubular urate transporters: apical URAT1 (SLC22A12) and
      basolateral URATv1/GLUT9 (SLC2A9). In contrast, the molecular mechanism(s) for
      renal urate secretion remain unknown. In this report, we demonstrate that an
      orphan transporter hNPT4 (human sodium phosphate transporter 4; SLC17A3) was a
      multispecific organic anion efflux transporter expressed in the kidneys and
      liver. hNPT4 was localized at the apical side of renal tubules and functioned as
      a voltage-driven urate transporter. Furthermore, loop diuretics, such as
      furosemide and bumetanide, substantially interacted with hNPT4. Thus, this
      protein is likely to act as a common secretion route for both drugs and may play
      an important role in diuretics-induced hyperuricemia. The in vivo role of hNPT4
      was suggested by two hyperuricemia patients with missense mutations in SLC17A3.
      These mutated versions of hNPT4 exhibited reduced urate efflux when they were
      expressed in Xenopus oocytes. Our findings will complete a model of urate
      secretion in the renal tubular cell, where intracellular urate taken up via OAT1
      and/or OAT3 from the blood exits from the cell into the lumen via hNPT4.

PMID- 20810652
TI  - A plasma membrane wound proteome: reversible externalization of intracellular
      proteins following reparable mechanical damage.
AB  - Cells in mechanically active tissues undergo constant plasma membrane damage that
      must be repaired to allow survival. To identify wound-associated proteins, a cell
      impermeant, thiol-reactive biotinylation reagent was used to label and
      subsequently isolate intracellular proteins that become exposed on the surface of
      cultured cells after plasma membrane damage induced by scraping from substratum
      or crushing with glass beads. Scrape-damaged cells survived injury and were
      capable of forming viable colonies. Proteins that were exposed to the cell
      surface were degraded or internalized a few seconds to several minutes after
      damage, except for vimentin, which was detectable on the cell surface for at
      least an hour after injury. Seven major biotinylated protein bands were
      identified on SDS-PAGE gels. Mass spectrometric studies identified cytoskeletal
      proteins (caldesmon-1 and vimentin), endoplasmic reticulum proteins (ERp57, ERp5,
      and HSP47), and nuclear proteins (lamin C, heterogeneous nuclear
      ribonucleoprotein F, and nucleophosmin-1) as major proteins exposed after injury.
      Although caldesmon was a major wound-associated protein in calpain small subunit
      knock-out fibroblasts, it was rapidly degraded in wild-type cells, probably by
      calpains. Lamin C exposure after wounding was most likely the consequence of
      nuclear envelope damage. These studies document major intracellular proteins
      associated with the cell surface of reversibly damaged somatic cells. The studies
      also show that externalization of some proteins reported to have physiologic or
      pathologic roles on the cell surface can occur in cells undergoing plasma
      membrane damage and subsequent repair.

PMID- 20810653
TI  - srGAP2 arginine methylation regulates cell migration and cell spreading through
      promoting dimerization.
AB  - The Slit-Robo GTPase-activating proteins (srGAPs) are critical for neuronal
      migration through inactivation of Rho GTPases Cdc42, Rac1, and RhoA. Here we
      report that srGAP2 physically interacts with protein arginine methyltransferase 5
      (PRMT5). srGAP2 localizes to the cytoplasm and plasma membrane protrusion. srGAP2
      knockdown reduces cell adhesion spreading and increases cell migration, but has
      no effect on cell proliferation. PRMT5 binds to the N terminus of srGAP2 (225-538
      aa) and methylates its C-terminal arginine residue Arg-927. The methylation
      mutant srGAP2-R927A fails to rescue the cell spreading rate, is unable to
      localize to the plasma membrane leading edge, and perturbs srGAP2 homodimer
      formation mediated by the F-BAR domain. These results suggest that srGAP2
      arginine methylation plays important roles in cell spreading and cell migration
      through influencing membrane protrusion.

PMID- 20810655
TI  - Substrate binding mechanism of a type I extradiol dioxygenase.
AB  - A meta-cleavage pathway for the aerobic degradation of aromatic hydrocarbons is
      catalyzed by extradiol dioxygenases via a two-step mechanism: catechol substrate
      binding and dioxygen incorporation. The binding of substrate triggers the release
      of water, thereby opening a coordination site for molecular oxygen. The crystal
      structures of AkbC, a type I extradiol dioxygenase, and the enzyme substrate (3
      methylcatechol) complex revealed the substrate binding process of extradiol
      dioxygenase. AkbC is composed of an N-domain and an active C-domain, which
      contains iron coordinated by a 2-His-1-carboxylate facial triad motif. The C
      domain includes a beta-hairpin structure and a C-terminal tail. In substrate
      bound AkbC, 3-methylcatechol interacts with the iron via a single hydroxyl group,
      which represents an intermediate stage in the substrate binding process.
      Structure-based mutagenesis revealed that the C-terminal tail and beta-hairpin
      form part of the substrate binding pocket that is responsible for substrate
      specificity by blocking substrate entry. Once a substrate enters the active site,
      these structural elements also play a role in the correct positioning of the
      substrate. Based on the results presented here, a putative substrate binding
      mechanism is proposed.

PMID- 20810654
TI  - Cell cycle-dependent regulation of the forkhead transcription factor FOXK2 by
      CDK.cyclin complexes.
AB  - Several mammalian forkhead transcription factors have been shown to impact on
      cell cycle regulation and are themselves linked to cell cycle control systems.
      Here we have investigated the little studied mammalian forkhead transcription
      factor FOXK2 and demonstrate that it is subject to control by cell cycle
      regulated protein kinases. FOXK2 exhibits a periodic rise in its phosphorylation
      levels during the cell cycle, with hyperphosphorylation occurring in mitotic
      cells. Hyperphosphorylation occurs in a cyclin-dependent kinase (CDK).cyclin
      dependent manner with CDK1.cyclin B as the major kinase complex, although CDK2
      and cyclin A also appear to be important. We have mapped two CDK phosphorylation
      sites, serines 368 and 423, which play a role in defining FOXK2 function through
      regulating its stability and its activity as a transcriptional repressor protein.
      These two CDK sites appear vital for FOXK2 function because expression of a
      mutant lacking these sites cannot be tolerated and causes apoptosis.

PMID- 20810657
TI  - A key role for the phosphorylation of Ser440 by the cyclic AMP-dependent protein
      kinase in regulating the activity of the Src homology 2 domain-containing
      Inositol 5'-phosphatase (SHIP1).
AB  - The Src homology 2 domain-containing inositol 5'-phosphatase 1 (SHIP1)
      dephosphorylates phosphatidylinositol 3,4,5-trisphosphate to phophatidylinositol
      3,4-bisphosphate in hematopoietic cells to regulate multiple cell signaling
      pathways. SHIP1 can be phosphorylated by the cyclic AMP-dependent protein kinase
      (PKA), resulting in an increase in SHIP1 activity (Zhang, J., Walk, S. F.,
      Ravichandran, K. S., and Garrison, J. C. (2009) J. Biol. Chem. 284, 20070-20078).
      Using a combination of approaches, we identified the serine residue regulating
      SHIP1 activity. After mass spectrometric identification of 17 serine and
      threonine residues on SHIP1 as being phosphorylated by PKA in vitro, studies with
      truncation mutants of SHIP1 narrowed the phosphorylation site to the catalytic
      region between residues 400 and 866. Of the two candidate phosphorylation sites
      located in this region (Ser(440) and Ser(774)), only mutation of Ser(440) to Ala
      abolished the ability of PKA to phosphorylate the purified, catalytic domain of
      SHIP1 (residues 401-866). Mutation of Ser(440) to Ala in full-length SHIP1
      abrogated the ability of PKA to increase the activity of SHIP1 in mammalian
      cells. Using flow cytometry, we found that the PKA activator, Sp-adenosine 3',5'
      cyclic monophosphorothioate triethylammonium salt hydrate (Sp-cAMPS) blunted the
      phosphorylation of Akt downstream of B cell antigen receptor engagement in SHIP1
      null DT40 B lymphocytes expressing native mouse SHIP1. The inhibitory effect of
      Sp-cAMPS was absent in cells expressing the S440A mutant of SHIP1. These results
      suggest that activation of SHIP1 by PKA via phosphorylation on Ser(440) is an
      important regulatory event in hematopoietic cells.

PMID- 20810656
TI  - Loss of H3 K79 trimethylation leads to suppression of Rtt107-dependent DNA damage
      sensitivity through the translesion synthesis pathway.
AB  - Genomic integrity is maintained by the coordinated interaction of many DNA damage
      response pathways, including checkpoints, DNA repair processes, and cell cycle
      restart. In Saccharomyces cerevisiae, the BRCA1 C-terminal domain-containing
      protein Rtt107/Esc4 is required for restart of DNA replication after successful
      repair of DNA damage and for cellular resistance to DNA-damaging agents. Rtt107
      and its interaction partner Slx4 are phosphorylated during the initial phase of
      DNA damage response by the checkpoint kinases Mec1 and Tel1. Because the natural
      chromatin template plays an important role during the DNA damage response, we
      tested whether chromatin modifications affected the requirement for Rtt107 and
      Slx4 during DNA damage repair. Here, we report that the sensitivity to DNA
      damaging agents of rtt107Delta and slx4Delta mutants was rescued by inactivation
      of the chromatin regulatory pathway leading to H3 K79 trimethylation. Further
      analysis revealed that lack of Dot1, the H3 K79 methyltransferase, led to
      activation of the translesion synthesis pathway, thereby allowing the survival in
      the presence of DNA damage. The DNA damage-induced phosphorylation of Rtt107 and
      Slx4, which was mutually dependent, was not restored in the absence of Dot1. The
      antagonistic relationship between Rtt107 and Dot1 was specific for DNA damage
      induced phenotypes, whereas the genomic instability caused by loss of Rtt107 was
      not rescued. These data revealed a multifaceted functional relationship between
      Rtt107 and Dot1 in the DNA damage response and maintenance of genome integrity.

PMID- 20810658
TI  - Starch binding domain-containing protein 1/genethonin 1 is a novel participant in
      glycogen metabolism.
AB  - Stbd1 is a protein of previously unknown function that is most prevalent in liver
      and muscle, the major sites for storage of the energy reserve glycogen. The
      protein is predicted to contain a hydrophobic N terminus and a C-terminal CBM20
      glycan binding domain. Here, we show that Stbd1 binds to glycogen in vitro and
      that endogenous Stbd1 locates to perinuclear compartments in cultured mouse FL83B
      or Rat1 cells. When overexpressed in COSM9 cells, Stbd1 concentrated at enlarged
      perinuclear structures, co-localized with glycogen, the late endosomal/lysosomal
      marker LAMP1 and the autophagy protein GABARAPL1. Mutant Stbd1 lacking the N
      terminal hydrophobic segment had a diffuse distribution throughout the cell.
      Point mutations in the CBM20 domain did not change the perinuclear localization
      of Stbd1, but glycogen was no longer concentrated in this compartment. Stable
      overexpression of glycogen synthase in Rat1WT4 cells resulted in accumulation of
      glycogen as massive perinuclear deposits, where a large fraction of the
      detectable Stbd1 co-localized. Starvation of Rat1WT4 cells for glucose resulted
      in dissipation of the massive glycogen stores into numerous and much smaller
      glycogen deposits that retained Stbd1. In vitro, in cells, and in animal models,
      Stbd1 consistently tracked with glycogen. We conclude that Stbd1 is involved in
      glycogen metabolism by binding to glycogen and anchoring it to membranes, thereby
      affecting its cellular localization and its intracellular trafficking to
      lysosomes.

PMID- 20810659
TI  - Cytoplasmic body component TRIM5{alpha} requires lipid-enriched microdomains for
      efficient HIV-1 restriction.
AB  - TRIM5alpha is a member of the tripartite motif (TRIM) family of proteins and
      affects both early and late phases of the retroviral life cycle. Although
      TRIM5alpha multimerizes to form cytoplasmic bodies, which are thought to play an
      important role in viral restriction, the identity of TRIM5alpha-containing
      cytoplasmic bodies remains elusive. To better understand TRIM5alpha cytoplasmic
      body constituents and the cellular proteins that could be involved in the
      TRIM5alpha-mediated antiviral activities, we sought TRIM5alpha-binding factors.
      We identified a lipid microdomain protein flotillin-1/Reggie-2 as an interacting
      partner of TRIM5alpha via co-immunoprecipitation. Immunohistochemistry studies
      confirmed the co-localization of rhesus monkey TRIM5alpha (TRIM5alpharh)
      cytoplasmic bodies with flotillin-1/Reggie-2. Caveolin-1, another lipid
      microdomain-associated protein, also co-localized with TRIM5alpha cytoplasmic
      bodies. Intriguingly, disruption of cellular cholesterol by cyclodextrin
      perturbed TRIM5alpha cytoplasmic body formation. Furthermore, lipid starvation
      partially relieved the endogenous post-entry restriction of HIV-1 infection,
      which could be subsequently restored by lipid repletion. These observations
      indicate the involvement of cellular lipids in TRIM5alpha-mediated antiviral
      activities. Given that many viruses utilize cellular lipid microdomains for viral
      entry and assembly, it is plausible that lipid-enriched domains provide
      microenvironments where TRIM5alpha recognizes retroviral components.

PMID- 20810660
TI  - Rabconnectin-3 is a functional regulator of mammalian Notch signaling.
AB  - The Notch signaling pathway is important for cell fate decisions in embryonic
      development and adult life. Defining the functional importance of the Notch
      pathway in these contexts requires the elucidation of essential signal
      transduction components that have not been fully characterized. Here, we show
      that Rabconnectin-3B is required for the Notch pathway in mammalian cells. siRNA
      mediated silencing of Rabconnectin-3B in mammalian cells attenuated Notch
      signaling and disrupted the activation and nuclear accumulation of the Notch
      target Hes1. Rabconnectin-3B knockdown also disrupted V-ATPase activity in
      mammalian cells, consistent with previous observations in Drosophila.
      Pharmacological inhibition of the V-ATPase complex significantly reduced Notch
      signaling in mammalian cells. Finally, Rabconnectin-3B knockdown phenocopied
      functional disruption of Notch signaling during osteoclast differentiation.
      Collectively, these findings define an important role for Rabconnectin-3 and V
      ATPase activity in the Notch signaling pathway in mammalian cells.

PMID- 20810661
TI  - BRIZ1 and BRIZ2 proteins form a heteromeric E3 ligase complex required for seed
      germination and post-germination growth in Arabidopsis thaliana.
AB  - Ubiquitin pathway E3 ligases are an important component conferring specificity
      and regulation in ubiquitin attachment to substrate proteins. The Arabidopsis
      thaliana RING (Really Interesting New Gene) domain-containing proteins BRIZ1 and
      BRIZ2 are essential for normal seed germination and post-germination growth. Loss
      of either BRIZ1 (At2g42160) or BRIZ2 (At2g26000) results in a severe phenotype.
      Heterozygous parents produce progeny that segregate 3:1 for wild-type:growth
      arrested seedlings. Homozygous T-DNA insertion lines are recovered for BRIZ1 and
      BRIZ2 after introduction of a transgene containing the respective coding
      sequence, demonstrating that disruption of BRIZ1 or BRIZ2 in the T-DNA insertion
      lines is responsible for the observed phenotype. Both proteins have multiple
      predicted domains in addition to the RING domain as follows: a BRAP2 (BRCA1
      Associated Protein 2), a ZnF UBP (Zinc Finger Ubiquitin Binding protein), and a
      coiled-coil domain. In vitro, both BRIZ1 and BRIZ2 are active as E3 ligases but
      only BRIZ2 binds ubiquitin. In vitro synthesized and purified recombinant BRIZ1
      and BRIZ2 preferentially form hetero-oligomers rather than homo-oligomers, and
      the coiled-coil domain is necessary and sufficient for this interaction. BRIZ1
      and BRIZ2 co-purify after expression in tobacco leaves, which also requires the
      coiled-coil domain. BRIZ1 and BRIZ2 coding regions with substitutions in the RING
      domain are inactive in vitro and, after introduction, fail to complement their
      respective mutant lines. In our current model, BRIZ1 and BRIZ2 together are
      required for formation of a functional ubiquitin E3 ligase in vivo, and this
      complex is required for germination and early seedling growth.

PMID- 20810662
TI  - Specificity of Staphyloferrin B recognition by the SirA receptor from
      Staphylococcus aureus.
AB  - Many organisms use sophisticated systems to acquire growth-limiting iron. Iron
      limitation is especially apparent in bacterial pathogens of mammalian hosts where
      free iron concentrations are physiologically negligible. A common strategy is to
      secrete low molecular weight iron chelators, termed siderophores, and express
      high affinity receptors for the siderophore-iron complex. Staphylococcus aureus,
      a widespread pathogen, produces two siderophores, staphyloferrin A (SA) and
      staphyloferrin B (SB). We have determined the crystal structure of the
      staphyloferrin B receptor, SirA, at high resolution in both the apo and Fe(III)
      SB (FeSB)-bound forms. SirA, a member of the class III binding protein family of
      metal receptors, has N- and C-terminal domains, each composed of mainly a beta
      stranded core and alpha-helical periphery. The domains are bridged by a single
      alpha-helix and together form the FeSB binding site. SB coordinates Fe(III)
      through five oxygen atoms and one nitrogen atom in distorted octahedral geometry.
      SirA undergoes conformational change upon siderophore binding, largely securing
      two loops from the C-terminal domain to enclose FeSB with a low nanomolar
      dissociation constant. The staphyloferrin A receptor, HtsA, homologous to SirA,
      also encloses its cognate siderophore (FeSA); however, the largest conformational
      rearrangements involve a different region of the C-terminal domain. FeSB is
      uniquely situated in the binding pocket of SirA with few of the contacting
      residues being conserved with those of HtsA interacting with FeSA. Although both
      SirA and HtsA bind siderophores from the same alpha-hydroxycarboxylate class, the
      unique structural features of each receptor provides an explanation for their
      distinct specificity.

PMID- 20810663
TI  - Tumor suppressor ras association domain family 5 (RASSF5/NORE1) mediates death
      receptor ligand-induced apoptosis.
AB  - Epigenetic silencing of RASSF (Ras association domain family) genes RASSF1 and
      RASSF5 (also called NORE1) by CpG hypermethylation is found frequently in many
      cancers. Although the physiological roles of RASSF1 have been studied in some
      detail, the exact functions of RASSF5 are not well understood. Here, we show that
      RASSF5 plays an important role in mediating apoptosis in response to death
      receptor ligands, TNF-alpha and TNF-related apoptosis-inducing ligand. Depletion
      of RASSF5 by siRNA significantly reduced TNF-alpha-mediated apoptosis, likely
      through its interaction with proapoptotic kinase MST1, a mammalian homolog of
      Hippo. Consistent with this, siRNA knockdown of MST1 also resulted in resistance
      to TNF-alpha-induced apoptosis. To further study the role of Rassf5 in vivo, we
      generated Rassf5-deficient mouse. Inactivation of Rassf5 in mouse embryonic
      fibroblasts (MEFs) resulted in resistance to TNF-alpha- and TNF-related apoptosis
      inducing ligand-mediated apoptosis. Importantly, Rassf5-null mice were
      significantly more resistant to TNF-alpha-induced apoptosis and failed to
      activate Mst1. Loss of Rassf5 also resulted in spontaneous immortalization of
      MEFs at earlier passages than the control MEFs, and Rassf5-null immortalized
      MEFs, but not the immortalized wild type MEFs, were fully transformed by K
      RasG12V. Together, our results demonstrate a direct role for RASSF5 in death
      receptor ligand-mediated apoptosis and provide further evidence for RASSF5 as a
      tumor suppressor.

PMID- 20810665
TI  - Molecular basis for cyclooxygenase inhibition by the non-steroidal anti
      inflammatory drug naproxen.
AB  - Naproxen ((S)-6-methoxy-alpha-methyl-2-naphthaleneacetic acid) is a powerful non
      selective non-steroidal anti-inflammatory drug that is extensively used as a
      prescription and over-the-counter medication. Naproxen exhibits gastrointestinal
      toxicity, but its cardiovascular toxicity may be reduced compared with other
      drugs in its class. Despite the fact that naproxen has been marketed for many
      years, the molecular basis of its interaction with cyclooxygenase (COX) enzymes
      is unknown. We performed a detailed study of naproxen-COX-2 interactions using
      site-directed mutagenesis, structure-activity analysis, and x-ray
      crystallography. The results indicate that each of the pendant groups of the
      naphthyl scaffold are essential for COX inhibition, and only minimal
      substitutions are tolerated. Mutation of Trp-387 to Phe significantly reduced
      inhibition by naproxen, a result that appears unique to this inhibitor.
      Substitution of S or CH(2) for the O atom of the p-methoxy group yielded analogs
      that were not affected by the W387F substitution and that exhibited increased COX
      2 selectivity relative to naproxen. Crystallization and x-ray analysis yielded
      structures of COX-2 complexed to naproxen and its methylthio analog at 1.7 and
      2.3 A resolution, respectively. The combination of mutagenesis, structure
      analysis, and x-ray crystallography provided comprehensive information on the
      unique interactions responsible for naproxen binding to COX-2.

PMID- 20810664
TI  - Crystal structure of the Src family kinase Hck SH3-SH2 linker regulatory region
      supports an SH3-dominant activation mechanism.
AB  - Most mammalian cell types depend on multiple Src family kinases (SFKs) to
      regulate diverse signaling pathways. Strict control of SFK activity is essential
      for normal cellular function, and loss of kinase regulation contributes to
      several forms of cancer and other diseases. Previous x-ray crystal structures of
      the SFKs c-Src and Hck revealed that intramolecular association of their Src
      homology (SH) 3 domains and SH2 kinase linker regions has a key role in down
      regulation of kinase activity. However, the amino acid sequence of the Hck linker
      represents a suboptimal ligand for the isolated SH3 domain, suggesting that it
      may form the polyproline type II helical conformation required for SH3 docking
      only in the context of the intact structure. To test this hypothesis directly, we
      determined the crystal structure of a truncated Hck protein consisting of the SH2
      and SH3 domains plus the linker. Despite the absence of the kinase domain, the
      structures and relative orientations of the SH2 and SH3 domains in this shorter
      protein were very similar to those observed in near full-length, down-regulated
      Hck. However, the SH2 kinase linker adopted a modified topology and failed to
      engage the SH3 domain. This new structure supports the idea that these
      noncatalytic regions work together as a "conformational switch" that modulates
      kinase activity in a manner unique to the SH3 domain and linker topologies
      present in the intact Hck protein. Our results also provide fresh structural
      insight into the facile induction of Hck activity by HIV-1 Nef and other Hck SH3
      domain binding proteins and implicate the existence of innate conformational
      states unique to individual Src family members that "fine-tune" their
      sensitivities to activation by SH3-based ligands.

PMID- 20810666
TI  - Founder population-specific HapMap panel increases power in GWA studies through
      improved imputation accuracy and CNV tagging.
AB  - The combining of genome-wide association (GWA) data across populations represents
      a major challenge for massive global meta-analyses. Genotype imputation using
      densely genotyped reference samples facilitates the combination of data across
      different genotyping platforms. HapMap data is typically used as a reference for
      single nucleotide polymorphism (SNP) imputation and tagging copy number
      polymorphisms (CNPs). However, the advantage of having population-specific
      reference panels for founder populations has not been evaluated. We looked at the
      properties and impact of adding 81 individuals from a founder population to
      HapMap3 reference data on imputation quality, CNP tagging, and power to detect
      association in simulations and in an independent cohort of 2138 individuals. The
      gain in SNP imputation accuracy was highest among low-frequency markers (minor
      allele frequency [MAF] < 5%), for which adding the population-specific samples to
      the reference set increased the median R(2) between imputed and genotyped SNPs
      from 0.90 to 0.94. Accuracy also increased in regions with high recombination
      rates. Similarly, a reference set with population-specific extension facilitated
      the identification of better tag-SNPs for a subset of CNPs; for 4% of CNPs the
      R(2) between SNP genotypes and CNP intensity in the independent population cohort
      was at least twice as high as without the extension. We conclude that even a
      relatively small population-specific reference set yields considerable benefits
      in SNP imputation, CNP tagging accuracy, and the power to detect associations in
      founder populations and population isolates in particular.

PMID- 20810667
TI  - Systematic comparison of three genomic enrichment methods for massively parallel
      DNA sequencing.
AB  - Massively parallel DNA sequencing technologies have greatly increased our ability
      to generate large amounts of sequencing data at a rapid pace. Several methods
      have been developed to enrich for genomic regions of interest for targeted
      sequencing. We have compared three of these methods: Molecular Inversion Probes
      (MIP), Solution Hybrid Selection (SHS), and Microarray-based Genomic Selection
      (MGS). Using HapMap DNA samples, we compared each of these methods with respect
      to their ability to capture an identical set of exons and evolutionarily
      conserved regions associated with 528 genes (2.61 Mb). For sequence analysis, we
      developed and used a novel Bayesian genotype-assigning algorithm, Most Probable
      Genotype (MPG). All three capture methods were effective, but sensitivities
      (percentage of targeted bases associated with high-quality genotypes) varied for
      an equivalent amount of pass-filtered sequence: for example, 70% (MIP), 84%
      (SHS), and 91% (MGS) for 400 Mb. In contrast, all methods yielded similar
      accuracies of >99.84% when compared to Infinium 1M SNP BeadChip-derived genotypes
      and >99.998% when compared to 30-fold coverage whole-genome shotgun sequencing
      data. We also observed a low false-positive rate with all three methods; of the
      heterozygous positions identified by each of the capture methods, >99.57% agreed
      with 1M SNP BeadChip, and >98.840% agreed with the whole-genome shotgun data. In
      addition, we successfully piloted the genomic enrichment of a set of 12 pooled
      samples via the MGS method using molecular bar codes. We find that these three
      genomic enrichment methods are highly accurate and practical, with sensitivities
      comparable to that of 30-fold coverage whole-genome shotgun data.

PMID- 20810668
TI  - Comprehensive annotation of the transcriptome of the human fungal pathogen
      Candida albicans using RNA-seq.
AB  - Candida albicans is the major invasive fungal pathogen of humans, causing
      diseases ranging from superficial mucosal infections to disseminated, systemic
      infections that are often lifethreatening. We have used massively parallel high
      throughput sequencing of cDNA (RNA-seq) to generate a high-resolution map of the
      C. albicans transcriptome under several different environmental conditions. We
      have quantitatively determined all of the regions that are transcribed under
      these different conditions, and have identified 602 novel transcriptionally
      active regions (TARs) and numerous novel introns that are not represented in the
      current genome annotation. Interestingly, the expression of many of these TARs is
      regulated in a condition-specific manner. This comprehensive transcriptome
      analysis significantly enhances the current genome annotation of C. albicans, a
      necessary framework for a complete understanding of the molecular mechanisms of
      pathogenesis for this important eukaryotic pathogen.

PMID- 20810669
TI  - Metformin suppresses colorectal aberrant crypt foci in a short-term clinical
      trial.
AB  - The biguanide metformin is widely used for treating diabetes mellitus. We
      previously showed the chemopreventive effect of metformin in two rodent models of
      colorectal carcinogenesis. However, besides epidemiologic studies, little is
      known about the effects of metformin on human colorectal carcinogenesis. The
      objective of this pilot study was to evaluate the chemopreventive effect of
      metformin on rectal aberrant crypt foci (ACF), which are an endoscopic surrogate
      marker of colorectal cancer. We prospectively randomized 26 nondiabetic patients
      with ACF to treatment with metformin (250 mg/d, n = 12) or no treatment (control,
      n = 14); 23 patients were evaluable for end point analyses (9 metformin and 14
      control); the two groups were similar in ACF number and other baseline clinical
      characteristics. Magnifying colonoscopy determined the number of rectal ACF in
      each patient at baseline and after 1 month in a blinded fashion (as were all
      laboratory end point analyses). We also examined proliferative activity in
      colonic epithelium (via proliferating cell nuclear antigen labeling index) and
      apoptotic activity (via terminal deoxynucleotidyl transferase dUTP nick-end
      labeling). At 1 month, the metformin group had a significant decrease in the mean
      number of ACF per patient (8.78 +/- 6.45 before treatment versus 5.11 +/- 4.99 at
      1 month, P = 0.007), whereas the mean ACF number did not change significantly in
      the control group (7.23 +/- 6.65 versus 7.56 +/- 6.75, P = 0.609). The
      proliferating cell nuclear antigen index was significantly decreased and the
      apoptotic cell index remained unaltered in normal rectal epithelium in metformin
      patients. This first reported trial of metformin for inhibiting colorectal
      carcinogenesis in humans provides preliminary evidence that metformin suppresses
      colonic epithelial proliferation and rectal ACF formation in humans, suggesting
      its promise for the chemoprevention of colorectal cancer.

PMID- 20810670
TI  - Metformin and other biguanides in oncology: advancing the research agenda.
AB  - Retrospective studies that may be impractical to confirm prospectively suggest
      that diabetics treated with metformin have a substantially reduced cancer burden
      compared with other diabetics. It is unclear if this reflects a chemopreventive
      effect, an effect on transformed cells, or both. It also remains to be
      established if these data have relevance to people without diabetes. Laboratory
      models, however, provide independent impressive evidence for the activity of
      metformin and other biguanides in both cancer treatment and chemoprevention.
      Investigations of mechanisms of action of biguanides have revealed considerable
      complexity and have identified important gaps in knowledge that should be
      addressed to ensure the optimal design of clinical trials of these agents. Such
      trials may define important new indications for biguanides in the prevention
      and/or treatment of many common cancers.

PMID- 20810671
TI  - Chemoprevention meets glucose control.
AB  - The report by Memmott et al. (beginning on page 1066 in this issue of the
      journal) assessing the efficacy of the antidiabetes drug metformin in a mouse
      model of lung carcinogenesis suggests protective effects via two possible
      avenues: Decreased circulating insulin and insulin-like growth factor levels and
      energy stress leading to inhibition of mammalian target of rapamycin signaling.
      These potential mechanisms are discussed in this perspective, as are their
      implications for cancer prevention and therapy.

PMID- 20810673
TI  - Population attributable risk for functional disability associated with chronic
      conditions in Canadian older adults.
AB  - OBJECTIVES: to investigate the population impact on functional disability of
      chronic conditions individually and in combination. METHODS: data from 9,008
      community-dwelling individuals aged 65 and older from the Canadian Study of
      Health and Aging (CSHA) were used to estimate the population attributable risk
      (PAR) for chronic conditions after adjusting for confounding variables.
      Functional disability was measured using activity of daily living (ADL) and
      instrumental activity of daily living (IADL). RESULTS: five chronic conditions
      (foot problems, arthritis, cognitive impairment, heart problems and vision) made
      the largest contribution to ADL- and IADL-related functional disabilities. There
      was variation in magnitude and ranking of population attributable risk (PAR) by
      age, sex and definition of disability. All chronic conditions taken
      simultaneously accounted for about 66% of the ADL-related disability and almost
      50% of the IADL-related disability. CONCLUSIONS: in community-dwelling older
      adults, foot problems, arthritis, cognitive impairment, heart problems and vision
      were the major determinants of disability. Attempts to reduce disability burden
      in older Canadians should target these chronic conditions; however, preventive
      interventions will be most efficient if they recognize the differences in the
      drivers of PAR by sex, age group and type of functional disability being
      targeted.

PMID- 20810672
TI  - Metformin prevents tobacco carcinogen--induced lung tumorigenesis.
AB  - Activation of the mammalian target of rapamycin (mTOR) pathway is an important
      and early event in tobacco carcinogen-induced lung tumorigenesis, and therapies
      that target mTOR could be effective in the prevention or treatment of lung
      cancer. The biguanide metformin, which is widely prescribed for the treatment of
      type II diabetes, might be a good candidate for lung cancer chemoprevention
      because it activates AMP-activated protein kinase (AMPK), which can inhibit the
      mTOR pathway. To test this, A/J mice were treated with oral metformin after
      exposure to the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK). Metformin reduced lung tumor burden by up to 53% at steady-state plasma
      concentrations that are achievable in humans. mTOR was inhibited in lung tumors
      but only modestly. To test whether intraperitoneal administration of metformin
      might improve mTOR inhibition, we injected mice and assessed biomarkers in liver
      and lung tissues. Plasma levels of metformin were significantly higher after
      injection than oral administration. In liver tissue, metformin activated AMPK and
      inhibited mTOR. In lung tissue, metformin did not activate AMPK but inhibited
      phosphorylation of insulin-like growth factor-I receptor/insulin receptor (IGF
      1R/IR), Akt, extracellular signal-regulated kinase (ERK), and mTOR. This
      suggested that metformin indirectly inhibited mTOR in lung tissue by decreasing
      activation of insulin-like growth factor-I receptor/insulin receptor and Akt
      upstream of mTOR. Based on these data, we repeated the NNK-induced lung
      tumorigenesis study using intraperitoneal administration of metformin. Metformin
      decreased tumor burden by 72%, which correlated with decreased cellular
      proliferation and marked inhibition of mTOR in tumors. These studies show that
      metformin prevents tobacco carcinogen-induced lung tumorigenesis and support
      clinical testing of metformin as a chemopreventive agent.

PMID- 20810674
TI  - Special article: an optimistic prognosis for the clinical utility of laboratory
      test data.
AB  - It is hoped that anesthesiologists and other clinicians will be able to
      increasingly rely upon laboratory test data to improve the perioperative care of
      patients. However, it has been suggested that in order for a laboratory test to
      have clinically useful diagnostic performance characteristics (sensitivity and
      specificity), its performance must be considerably better than those that have
      been evaluated in most etiologic or epidemiologic studies. This pessimism about
      the clinical utility of laboratory tests is based upon the untested assumption
      that laboratory data are normally distributed within case and control
      populations. We evaluated the data distribution for 700 commonly ordered
      laboratory tests, and found that the vast majority (99%) do not have a normal
      distribution. The deviation from normal was most pronounced at extreme values,
      which had a large quantitative effect on laboratory test performance. At the
      sensitivity and specificity values required for diagnostic utility, the minimum
      required odds ratios for laboratory tests with a nonnormal data distribution were
      significantly smaller (by orders of magnitude) than for tests with a normal
      distribution. By evaluating the effect that the data distribution has on
      laboratory test performance, we have arrived at the more optimistic outlook that
      it is feasible to produce laboratory tests with diagnostically useful performance
      characteristics. We also show that moderate errors in the classification of
      outcome variables (e.g., death vs. survival at a specified end point) have a
      small impact on test performance, which is of importance for outcomes research
      that uses anesthesia information management systems. Because these analyses
      typically seek to identify factors associated with an undesirable outcome, the
      data distributions of the independent variables need to be considered when
      interpreting the odds ratios obtained from such investigations.

PMID- 20810675
TI  - Adaptive support ventilation with protocolized de-escalation and escalation does
      not accelerate tracheal extubation of patients after nonfast-track cardiothoracic
      surgery.
AB  - BACKGROUND: It is uncertain whether adaptive support ventilation (ASV)
      accelerates weaning of nonfast-track cardiothoracic surgery patients. A lower
      operator set %-minute ventilation with ASV may allow for an earlier definite
      switch from controlled to assisted ventilation, potentially hastening tracheal
      extubation. We hypothesized that ASV using protocolized de-escalation and
      escalation of operator set %-minute ventilation (ASV-DE) reduces time until
      tracheal extubation compared with ASV using a fixed operator set %-minute
      ventilation (standard ASV) in uncomplicated patients after nonfast-track coronary
      artery bypass graft. METHODS: We performed a randomized controlled trial
      comparing ASV-DE with standard ASV. With ASV-DE, as soon as body temperature was
      >35.0 degrees C with pH >7.25, operator set %-minute ventilation was decreased
      stepwise to a minimum of 70%. RESULTS: Sixty-three patients were randomized to
      ASV-DE, and 63 patients to standard ASV. The duration of mechanical ventilation
      was not different between groups (10.8 [6.5-16.1] vs 10.7 [6.6-13.9] hours, ASV
      DE versus standard ASV; P = 0.32). Time until the first assisted breathing period
      was shorter (3.1 [2.0-6.7] vs 3.9 [2.1-7.5] hours) and the number of assisted
      ventilation episodes was higher (78 [34-176] vs 57 [32-116] episodes), but
      differences did not reach statistical significance. The duration of assisted
      ventilation episodes that ended with tracheal extubation was different between
      groups (2.5 [0.9-4.6] vs 1.4 [0.3-3.5] hours, ASV-DE versus standard ASV; P <
      0.05). CONCLUSION: Compared with standard ASV, weaning of patients after nonfast
      track coronary artery bypass graft using ASV with protocolized de-escalation and
      escalation does not shorten time to tracheal extubation.

PMID- 20810676
TI  - Special article: personal protective equipment for care of pandemic influenza
      patients: a training workshop for the powered air purifying respirator.
AB  - Virulent respiratory infectious diseases may present a life-threatening risk for
      health care professionals during aerosol-generating procedures, including
      endotracheal intubation. The 2009 Pandemic Influenza A (H1N1) brings this concern
      to the immediate forefront. The Centers for Disease Control and Prevention have
      stated that, when performing or participating in aerosol-generating procedures on
      patients with virulent contagious respiratory diseases, health care professionals
      must wear a minimum of the N95 respirator, and they may wish to consider using
      the powered air purifying respirator (PAPR). For influenza and other diseases
      transmitted by both respiratory and contact modes, protective respirators must be
      combined with contact precautions. The PAPR provides 2.5 to 100 times greater
      protection than the N95, when used within the context of an Occupational Safety
      and Health Administration-compliant respiratory protection program. The relative
      protective capability of a respirator is quantified using the assigned protection
      factor. The level of protection designated by the APF can only be achieved with
      appropriate training and correct use of the respirator. Face seal leakage limits
      the protective capability of the N95 respirator, and fit testing does not assure
      the ability to maintain a tight face seal. The protective capability of the PAPR
      will be defeated by improper handling of contaminated equipment, incorrect
      assembly and maintenance, and improper don (put on) and doff (take off)
      procedures. Stress, discomfort, and physical encumbrance may impair performance.
      Acclimatization through training will mitigate these effects. Training in the use
      of PAPRs in advance of their need is strongly advised. "Just in time" training is
      unlikely to provide adequate preparation for groups of practitioners requiring
      specialized personal protective equipment during a pandemic. Employee health
      departments in hospitals may not presently have a PAPR training program in place.
      Anesthesia and critical care providers would be well advised to take the lead in
      working with their hospitals' employee health departments to establish a PAPR
      training program where none exists. User instructions state that the PAPR should
      not be used during surgery because it generates positive outward airflow, and may
      increase the risk of wound infection. Clarification of this prohibition and
      acceptable solutions are currently lacking and need to be addressed. The surgical
      hood system is not an acceptable alternative. We provide on line a PAPR training
      workshop. Supporting information is presented here. Anesthesia and critical care
      providers may use this workshop to supplement, but not substitute for, the
      manufacturers' detailed use and maintenance instructions.

PMID- 20810677
TI  - Two serial check valves can prevent cross-contamination through intravenous
      tubing during total intravenous anesthesia.
AB  - BACKGROUND: Nonsterile handling of propofol for anesthesia has been linked with
      severe sepsis and death. Placing a single check valve in the IV tubing does not
      prevent retrograde ascension of pathogens into propofol-filled syringes, so we
      designed an IV tubing set with multiple check valves. To estimate the efficacy of
      this design, we measured the concentration of pathogens detected upstream in the
      IV tubing in relation to the pathogen concentration in a model of a contaminated
      patient. METHODS: A glass container with a rubber sealed port was filled with a
      suspension of either bacteria or phagocytes and kept at 37 degrees C
      ("contaminated patient" model). A bag of normal saline was connected to an IV
      cannula, punctured through the rubber sealed port of the patient model. Two
      additional sidestream infusion lines were connected to syringes in 2 standard
      infusion pumps. One of the syringes contained propofol and the other contained
      normal saline as a substitute for an opioid preparation. After 5 hours of
      infusion, we obtained samples from different parts of the infusion lines and
      syringes. The samples were streaked out on blood agar plates and incubated at 37
      degrees C for 24 hours. We repeated this experiment with 6 different pathogens.
      RESULTS: We incubated 825 agar plates. Whereas the concentration of bacteria and
      phagocytes in the "patient" had significantly increased during the 5-hour
      experiments (positive control), no bacterial growth could be detected in any of
      the incubated plates. CONCLUSION: The data from this experimental setting suggest
      that the design with multiple check valves in paired configuration prevents
      retrograde contamination. Of note, this does not permit the reuse of propofol
      syringes because reusing is against the manufacturer's recommendations.

PMID- 20810678
TI  - Mycoplasma agassizii strain variation and distinct host antibody responses
      explain differences between enzyme-linked immunosorbent assays and Western blot
      assays.
AB  - The precarious status of desert (Gopherus agassizii) and gopher (G. polyphemus)
      tortoises has resulted in conservation efforts that now include health assessment
      as an important component of management decision-making. Mycoplasmal upper
      respiratory tract disease (URTD) is one of very few diseases in chelonians for
      which comprehensive and rigorously validated diagnostic tests exist. In this
      study, serum samples obtained from eight Gopherus tortoises documented at
      necropsy to (i) be enzyme-linked immunosorbent assay (ELISA) seropositive using
      the PS6 antigen, (ii) be infected with Mycoplasma agassizii as indicated by
      direct isolation of the pathogen from the respiratory surfaces, and (iii) have
      histological lesions of mycoplasmal URTD were used to evaluate four distinct
      clinical isolates of M. agassizii as antigens for ELISA and Western blot
      analyses. Each animal sample reacted in the Western blot with its homologous M.
      agassizii strain, but recognition of heterologous M. agassizii strains was
      variable. Further, individual animals varied significantly with respect to the
      specific proteins recognized by the humoral immune response. An additional 114
      Gopherus serum samples were evaluated using ELISA antigens prepared from the four
      distinct M. agassizii strains; A405 values were significantly correlated (r2
      goodness of fit range, 0.708 to 0.771; P < 0.0001) for all antigens tested. The
      results confirm that strain variation is responsible for the observed differences
      between Western blot binding patterns. Thus, reliance on a single M. agassizii
      strain as an antigen in Western blot assays may provide false-negative results.
      This could have adverse consequences for the well-being of these environmentally
      sensitive hosts if false-negative animals were relocated to sites consisting of
      true-negative populations.

PMID- 20810680
TI  - A heterologous MF59-adjuvanted H5N1 prepandemic influenza booster vaccine induces
      a robust, cross-reactive immune response in adults and the elderly.
AB  - Immunogenicity and safety of a booster dose of an MF59-adjuvanted H5N1 vaccine
      containing 7.5 MUg A/turkey/Turkey/1/2005-like (clade 2.2) H5N1 hemagglutinin,
      given approximately 18 months after primary vaccination with a heterologous
      strain, were evaluated. The booster vaccine was well tolerated and induced a
      robust, cross-reactive immune response.

PMID- 20810679
TI  - Development of a Bacillus subtilis-based rotavirus vaccine.
AB  - Bacillus subtilis vaccine strains engineered to express either group A bovine or
      murine rotavirus VP6 were tested in adult mice for their ability to induce immune
      responses and provide protection against rotavirus challenge. Mice were
      inoculated intranasally with spores or vegetative cells of the recombinant
      strains of B. subtilis. To enhance mucosal immunity, whole cholera toxin (CT) or
      a mutant form (R192G) of Escherichia coli heat-labile toxin (mLT) were included
      as adjuvants. To evaluate vaccine efficacy, the immunized mice were challenged
      orally with EDIM EW murine rotavirus and monitored daily for 7 days for virus
      shedding in feces. Mice immunized with either VP6 spore or VP6 vegetative cell
      vaccines raised serum anti-VP6 IgG enzyme-linked immunosorbent assay (ELISA)
      titers, whereas only the VP6 spore vaccines generated fecal anti-VP6 IgA ELISA
      titers. Mice in groups that were immunized with VP6 spore vaccines plus CT or mLT
      showed significant reductions in virus shedding, whereas the groups of mice
      immunized with VP6 vegetative cell vaccines showed no difference in virus
      shedding compared with mice immunized with control spores or cells. These results
      demonstrate that intranasal inoculation with B. subtilis spore-based rotavirus
      vaccines is effective in generating protective immunity against rotavirus
      challenge in mice.

PMID- 20810681
TI  - Induction of both cellular and humoral immunity following a rational prime-boost
      immunization regimen that incorporates recombinant ovine atadenovirus and fowlpox
      virus.
AB  - Recombinant fowlpox viruses (rFPV) and ovine atadenoviruses (rOAdV) are being
      developed as safe, nonpathogenic, prophylactic and therapeutic vaccine vectors.
      There is scope, however, to improve the limited immune responses elicited by each
      of these vaccine vectors. Using previously determined and optimized routes of
      administration and viral doses, we characterized the primary adaptive immune
      responses elicited by recombinant variants of each virus. We demonstrate the
      contrasting nature of the response elicited by each recombinant virus. Whereas
      rFPV generates predominately cell-mediated immunity to our nominal target
      antigen, ovalbumin (OVA), rOAdV drives strong humoral responses. By defining the
      time taken to achieve maximal cytotoxic T cell responses and by studying the
      different patterns and kinetics of major histocompatibility complex class I
      restricted OVA antigen expression postimmunization, we proposed a heterologous
      prime-boost regimen of immunization with rOAdV followed by rFPV. The subsequent
      experimental results showed that this approach produced robust cell-mediated and
      humoral immune responses against OVA that, importantly, were accompanied by weak
      anti-viral vector antibody responses. These results, therefore, represent a novel
      and potentially clinically applicable way to achieve broadly based and effective
      immunity to the antigens encoded by vectored vaccines.

PMID- 20810682
TI  - An evaluation of the conductivity profile in the somatosensory barrel cortex of
      Wistar rats.
AB  - Microelectrode arrays used to record local field potentials from the brain are
      being built with increasingly more spatial resolution, ranging from the initially
      developed laminar arrays to those with planar and three-dimensional (3D) formats.
      In parallel with such development in recording techniques, current source density
      (CSD) analyses have recently been expanded up to the continuous-3D form.
      Unfortunately, the effect of the conductivity profile on the CSD analysis
      performed with contemporary microelectrode arrays has not yet been evaluated and
      most of the studies assumed it was homogeneous and isotropic. In this study, we
      measured the conductivity profile in the somatosensory barrel cortex of Wistar
      rats. To that end, we combined multisite electrophysiological data recorded with
      a homemade assembly of silicon-based probes and a nonlinear least-squares
      algorithm that implicitly assumed that the cerebral cortex of rodents could be
      locally approximated as a layered anisotropic spherical volume conductor. The
      eccentricity of the six cortical layers in the somatosensory barrel cortex was
      evaluated from postmortem histological images. We provided evidence for the local
      spherical character of the entire barrels field, with concentric cortical layers.
      We found significant laminar dependencies in the conductivity values with
      radial/tangential anisotropies. These results were in agreement with the layer
      dependent orientations of myelinated axons, but hardly related to densities of
      cells. Finally, we demonstrated through simulations that ignoring the real
      conductivity profile in the somatosensory barrel cortex of rats caused
      considerable errors in the CSD reconstruction, with pronounced effects on the
      continuous-3D form and charge-unbalanced CSD. We concluded that the conductivity
      profile must be included in future developments of CSD analysis, especially for
      rodents.

PMID- 20810683
TI  - Selective activation of neuronal targets with sinusoidal electric stimulation.
AB  - Electric stimulation of the CNS is being evaluated as a treatment modality for a
      variety of neurological, psychiatric, and sensory disorders. Despite considerable
      success in some applications, existing stimulation techniques offer little
      control over which cell types or neuronal substructures are activated by
      stimulation. The ability to more precisely control neuronal activation would
      likely improve the clinical outcomes associated with these applications. Here, we
      show that specific frequencies of sinusoidal stimulation can be used to
      preferentially activate certain retinal cell types: photoreceptors are activated
      at 5 Hz, bipolar cells at 25 Hz, and ganglion cells at 100 Hz. In addition, low
      frequency stimulation (<=25 Hz) did not activate passing axons but still elicited
      robust synaptically mediated responses in ganglion cells; therefore, elicited
      neural activity is confined to within a focal region around the stimulating
      electrode. Our results suggest that sinusoidal stimulation provides significantly
      improved control over elicited neural activity relative to conventional pulsatile
      stimulation.

PMID- 20810684
TI  - Changes in membrane potential and the intracellular calcium concentration during
      CSD and OGD in layer V and layer II/III mouse cortical neurons.
AB  - Cortical spreading depression (CSD) is an episode of electrical silence following
      intense neuronal activity that propagates across the cortex at ~3-6 mm/min and is
      associated with transient neuronal depolarization. CSD is benign in normally
      perfused brain tissue, but there is evidence suggesting that repetitive CSD
      contributes to infarct growth following focal ischemia. Studies to date have
      assumed that the cellular responses to CSD are uniform across neuronal types
      because there are no data to the contrary. In this study, we investigated the
      effect of CSD on membrane potential and the intracellular calcium concentration
      ([Ca(2+)](i)) of mouse layer V and layer II/III pyramidal neurons in brain
      slices. To place the data in context, we made similar measurements during anoxic
      depolarization induced by oxygen and glucose deprivation (OGD). The [Ca(2+)](i)
      was quantified using the low-affinity ratiometric indicator Fura-4F. During both
      CSD- and OGD-induced depolarization, the membrane potential approached 0 mV in
      all neurons. In layer V pyramids OGD resulted in an increase in [Ca(2+)](i) to a
      maximum of 3.69 +/- 0.73 (SD) MUM (n = 12), significantly greater than the
      increase to 1.81 +/- 0.70 MUM in CSD (n = 34; P < 0.0001). Membrane potential and
      [Ca(2+)](i) returned to nearly basal levels following CSD but not OGD. Layer
      II/III neurons responded to CSD with a greater peak increase in [Ca(2+)](i) than
      layer V neurons (2.88 +/- 0.6 MUM; n = 9; P < 0.01). We conclude there is a
      laminar difference in the response of pyramidal neurons to CSD; possible
      explanations are discussed.

PMID- 20810685
TI  - Decision-making, errors, and confidence in the brain.
AB  - To provide a fundamental basis for understanding decision-making and decision
      confidence, we analyze a neuronal spiking attractor-based model of decision
      making. The model predicts probabilistic decision-making with larger neuronal
      responses and larger functional magnetic resonance imaging (fMRI) blood-oxygen
      level-dependent (BOLD) responses on correct than on error trials because the
      spiking noise-influenced decision attractor state of the network is consistent
      with the external evidence. Moreover, the model predicts that the neuronal
      activity and the BOLD response will become larger on correct trials as the
      discriminability DeltaI increases and confidence increases and will become
      smaller as confidence decreases on error trials as DeltaI increases. Confidence
      is thus an emergent property of the model. In an fMRI study of an olfactory
      decision-making task, we confirm these predictions for cortical areas including
      medial prefrontal cortex and the cingulate cortex implicated in choice decision
      making, showing a linear increase in the BOLD signal with DeltaI on correct
      trials, and a linear decrease on error trials. These effects were not found in a
      control area, the orbitofrontal cortex, where reward value useful for the choice
      is represented on a continuous scale but that is not implicated in the choice
      itself. This provides a unifying approach to decision-making and decision
      confidence and to how spiking-related noise affects choice, confidence, synaptic
      and neuronal activity, and fMRI signals.

PMID- 20810687
TI  - Segmental oscillators in axial motor circuits of the salamander: distribution and
      bursting mechanisms.
AB  - The rhythmic and coordinated activation of axial muscles that underlie trunk
      movements during locomotion are generated by specialized networks in the spinal
      cord. The operation of these networks has been extensively investigated in
      limbless swimming vertebrates. But little is known about the architecture and
      functioning of the axial locomotor networks in limbed vertebrates. We
      investigated the rhythm-generating capacity of the axial segmental networks in
      the salamander (Pleurodeles waltlii). We recorded ventral root activity from
      hemisegments and segments that were surgically isolated from the mid-trunk cord
      and chemically activated with bath-applied N-methyl-d-aspartate (NMDA). We
      provide evidence that the rhythmogenic capacity of the axial network is
      distributed along the mid-trunk spinal cord without an excitability gradient. We
      demonstrate that the burst generation in a hemisegment depends on glutamatergic
      excitatory interactions. Reciprocal glycinergic inhibition between opposite
      hemisegments ensures left-right alternation and lowers the rhythm frequency in
      segments. Our results further suggest that persistent sodium current contributes
      to the rhythmic regenerating process both in hemisegments and segments. Burst
      termination in hemisegments is not achieved through the activation of apamine
      sensitive Ca(2+)-activated K(+) channels and burst termination in segments relies
      on crossed glycinergic inhibition. Together our results indicate that the basic
      design of the salamander axial network is similar to most of axial networks
      investigated in other vertebrates, albeit with some significant differences in
      the cellular mechanism that underlies segmental bursting. This finding supports
      the view of a phylogenetic conservation of basic building blocks of the axial
      locomotor network among the vertebrates.

PMID- 20810686
TI  - Sensory-spatial transformations in the left posterior parietal cortex may
      contribute to reach timing.
AB  - The posterior parietal cortex (PPC) contains viewer-centered spatial maps
      important for reaching movements. It is known that spatial reaching deficits
      emerge when this region is damaged, yet less is known about temporal deficits
      that may also emerge because of a failure in sensory-spatial transformations.
      This work introduces a new geometric measure to quantify multimodal sensory
      transformation and integration deficits affecting the tempo of reaching
      trajectories that are induced by injury to the left PPC. Erratic rates of
      positional change involving faulty maps from rotational angular displacements to
      translational linear displacements contributed to temporal abnormalities in the
      reach. Such disruptions were quantified with a time-invariant geometric measure.
      This measure, paired with an experimental paradigm that manipulated the source of
      visual guidance for reaches, was used to compare the performance of normal
      controls to those from a patient (T.R.) who had a lesion in his left-PPC. For
      controls, the source of visual guidance significantly scaled the tempo of target
      directed reaches but did not change the geometric measure. This was not the case
      in patient T.R., who altered this measure. With continuous, extrapersonal visual
      feedback of the target, however, these abnormalities improved. Vision of the
      target rather than vision of his moving hand also improved his arm-joint
      rotations for posture control. These results show that the left PPC is critically
      important for visuo-motor transformations that specifically rely on extrapersonal
      cues to align rotational-arm and linear-hand displacements and to continuously
      integrate their rates of change. The intactness of this system contributes to the
      fluidity of the reach's tempo.

PMID- 20810688
TI  - First trial postural reactions to unexpected balance disturbances: a comparison
      with the acoustic startle reaction.
AB  - Unexpected support-surface movements delivered during stance elicit "first trial"
      postural reactions, which are larger and cause greater instability compared with
      habituated responses. The nature of this first trial reaction remains unknown. We
      hypothesized that first trial postural reactions consist of a generalized startle
      reaction, with a similar muscle synergy as the acoustic startle response,
      combined with an automatic postural reaction. Therefore we compared acoustic
      startle responses to first trial postural reactions. Eight healthy subjects stood
      on a support surface that unexpectedly rotated backwards 10 times, followed by 10
      startling acoustic stimuli, or vice versa. Outcome measures included full body
      kinematics and surface EMG from muscles involved in startle reactions or postural
      control. Postural perturbations and startling acoustic stimuli both elicited a
      clear first trial reaction, as reflected by larger kinematic and EMG responses.
      The ensuing habituation rate to repeated identical stimuli was comparable for
      neck and trunk muscles in both conditions. Onset latencies in neck muscles
      occurred significantly later for first trial perturbations compared with startle
      responses, but earlier in trunk muscles. Our results show that platform tilting
      initially induces reactions larger than needed to maintain equilibrium. For neck
      and trunk muscles, these first trial postural reactions resembled acoustic
      startle reflexes. First trial postural reactions may be triggered by interaction
      of afferent volleys formed by somatosensory and vestibular inputs. Acoustic
      startle reactions may also be partially triggered by vestibular inputs. Similar
      muscle activation driven by vestibular inputs may be the common element of first
      trial postural responses and acoustic startle reactions.

PMID- 20810689
TI  - Collision-sensitive neurons in the optic tectum of the bullfrog, Rana
      catesbeiana.
AB  - In this study, we examined the neuronal correlates of frog collision avoidance
      behavior. Single unit recordings in the optic tectum showed that 11 neurons gave
      selective responses to objects approaching on a direct collision course. The
      collision-sensitive neurons exhibited extremely tight tuning for collision bound
      trajectories with mean half-width at half height values of 0.8 and 0.9 degrees 
      (n = 4) for horizontal and vertical deviations, respectively. The response of
      frog collision-sensitive neurons can be fitted by a function that simply
      multiplies the size dependence of its response, e(-alphatheta(t)), by the image's
      instantaneous angular velocity theta'(t). Using fitting analysis, we showed that
      the peak firing rate always occurred after the approaching object had reached a
      constant visual angle of 24.2 +/- 2.6 degrees  (mean +/- SD; n = 8), regardless
      of the approaching velocity. Moreover, a linear relationship was demonstrated
      between parameters l/v (l: object's half-size, v: approach velocity) and time-to
      collision (time difference between peak neuronal activity and the predicted
      collision) in the 11 collision-sensitive neurons. In addition, linear regression
      analysis was used to show that peak firing rate always occurred after the object
      had reached a constant angular size of 21.1 degrees  on the retina. The angular
      thresholds revealed by both theoretical analyses were comparable and showed a
      good agreement with that revealed by our previous behavioral experiments. This
      strongly suggests that the collision-sensitive neurons of the frog comprise a
      threshold detector, which triggers collision avoidance behavior.

PMID- 20810690
TI  - Exploratory movements determine cue weighting in haptic length perception of
      handheld rods.
AB  - In the present study, we sought to unravel how exploratory movements affect
      length perception of rods that are held in and wielded by hand. We manipulated
      the mechanical rod properties--mass (m), first moment of mass distribution (M),
      major principal moment of inertia (I(1))--individually, allowing us to assess the
      relative contribution of each of these mechanical variables to the perceptual
      judgment. Furthermore we developed a method to quantify the force components of
      the mechanical variables in the total of forces acting at the hand-rod interface,
      and we calculated each component's relative contribution. The laws of mechanics
      dictate that these relative force contributions depend on the characteristics of
      the exploratory movements performed. We found a clear relationship between the
      relative force contribution of the mechanical variables and their contribution to
      perceived rod length. This finding is the first quantitative demonstration that
      exploration style determines how much each mechanical variable influences length
      perception. Moreover, this finding suggested a cue weighting mechanism in which
      exploratory movements determine cue reliability (and thus cue weighting). We
      developed a cue combination model for which we first identified three length cues
      in the form of ratios between the mechanical variables. Second, we calculated the
      weights of these cues from the recorded rod movements. The model provided a
      remarkably good prediction of the experimental data. This strongly suggests that
      rod length perception by wielding is achieved through a weighted combination of
      three specific length cues, whereby the weighting depends on the characteristics
      of the exploratory movements.

PMID- 20810691
TI  - Variations in the TNF-alpha gene (TNF-alpha -308G->A) affect attention and action
      selection mechanisms in a dissociated fashion.
AB  - There is growing interest to understand the molecular basis of complex cognitive
      processes. While neurotransmitter systems have frequently been examined, other,
      for example neuroimmunological factors have attracted much less interest. Recent
      evidence suggests that the A allele of the tumor necrosis factor alpha (TNF
      alpha) 308G->A single nucleotide polymorphism (SNP; rs1800629) enhances cognitive
      functions. However, it is also known that TNF-alpha exerts divergent, region
      specific effects on neuronal functioning. Thus the finding that the A allele is
      associated with enhanced cognitive performance may be due to regionally specific
      effects of TNF-alpha. In this study, associations between the TNF-alpha -308G->A
      single nucleotide polymorphism (rs1800629) and cognitive function in an event
      related potential (ERP) study in healthy participants (n = 96) are investigated.
      We focus on subprocesses of stimulus-response compatibility that are known to be
      mediated by different brain systems. The results show a dissociative effect of
      the TNF- 308G->A SNP on ERPs reflecting attentional (N1) versus conflict and
      action selection processes [N2 and early-lateralized readiness potential (e-LRP)]
      between the AA/AG and the GG genotypes. Compared with the GG genotype group,
      attentional processes (N1) were enhanced in the combined AA/AG genotype group,
      while conflict processing functions (N2) and the selection of actions (LRP) were
      reduced. The results refine the picture of the effects of the TNF-alpha -308G->A
      SNP on cognitive functions and emphasize the known divergent effects of TNF-alpha
      on brain functions.

PMID- 20810692
TI  - Neural correlates of correct and errant attentional selection revealed through
      N2pc and frontal eye field activity.
AB  - The goal of this study was to obtain a better understanding of the physiological
      basis of errors of visual search. Previous research has shown that search errors
      occur when visual neurons in the frontal eye field (FEF) treat distractors as if
      they were targets. We replicated this finding during an inefficient form search
      and extended it by measuring simultaneously a macaque homologue of an event
      related potential indexing the allocation of covert attention known as the m
      N2pc. Based on recent work, we expected errors of selection in FEF to propagate
      to areas of extrastriate cortex responsible for allocating attention and
      implicated in the generation of the m-N2pc. Consistent with this prediction, we
      discovered that when FEF neurons selected a distractor instead of the search
      target, the m-N2pc shifted in the same, incorrect direction prior to the
      erroneous saccade. This suggests that such errors are due to a systematic
      misorienting of attention from the initial stages of visual processing. Our
      analyses also revealed distinct neural correlates of false alarms and guesses.
      These results demonstrate that errant gaze shifts during visual search arise from
      errant attentional processing.

PMID- 20810693
TI  - Reflexive limb selection and control of reach direction to moving targets in
      cats, monkeys, and humans.
AB  - When we reach for an object, we have to decide which arm to use and the direction
      in which to move. According to the established view, this is voluntarily
      controlled and programmed in advance in time-consuming and elaborate
      computations. Here, we systematically tested the motor strategy used by cats,
      monkeys, and humans when catching an object moving at high velocity to the left
      or right. In all species, targets moving to the right selectively initiated
      movement of the right forelimb and vice versa for targets moving to the left.
      Movements were from the start directed toward a prospective target position. In
      humans, the earliest onset of electromyographic activity from start of motion of
      the target ranged from 90 to 110 ms in different subjects. This indicates that
      the selection of the arm and specification of movement direction did not result
      from the subject's voluntary decision, but were determined in a reflex-like
      manner by the parameters of the target motion. As a whole the data suggest that
      control of goal-directed arm movement relies largely on an innate neuronal
      network that, when activated by the visual signal from the target, automatically
      guides the arm throughout the entire movement toward the target. In the view of
      the present data, parametric programming of reaching in advance seems to be
      superfluous.

PMID- 20810695
TI  - Trial-to-trial variability of spike response of V1 and saccadic response time.
AB  - Single neurons in the primary visual cortex (V1) show variability in spike
      activity in response to an identical visual stimulus. In the current study, we
      examined the behavioral significance of the variability in spike activity of V1
      neurons for visually guided saccades. We recorded single-cell activity from V1 of
      monkeys trained to detect and make saccades toward visual targets of varying
      contrast and analyzed trial-to-trial covariation between the onset time or firing
      rate of neural response and saccadic response time (RT). Neural latency (NL, the
      time of the first spike of neural response) was correlated with RT, whereas
      firing rate (FR) was not. When FR was computed with respect to target onset
      ignoring NL, a "false" correlation between FR and RT emerged. Multiple regression
      and partial correlation analyses on NL and FR for predictability of RT
      variability, as well as a simulation with artificial Poisson spike trains,
      supported the conclusion that the correlation between FR with respect to target
      onset and RT was mediated by a correlation between NL and RT, emphasizing the
      role of trial-to-trial variability of NL for extracting RT-related signals. We
      attempted to examine laminar differences in RT-related activity. Neurons recorded
      in the superficial layers tended to show a higher sensitivity to stimulus
      contrast and a lower correlation with RT compared with those in the lower layers,
      suggesting a sensory-to-motor transformation within V1 that follows the order of
      known anatomical connections. These results demonstrate that the trial-to-trial
      variability of neural response in V1 propagates to the stage of saccade
      execution, resulting in trial-to-trial variability of RT of a visually guided
      saccade.

PMID- 20810694
TI  - Unsupervised classification of high-frequency oscillations in human neocortical
      epilepsy and control patients.
AB  - High-frequency oscillations (HFOs) have been observed in animal and human
      intracranial recordings during both normal and aberrant brain states. It has been
      proposed that the relationship between subclasses of these oscillations can be
      used to identify epileptic brain. Studies of HFOs in epilepsy have been hampered
      by selection bias arising primarily out of the need to reduce the volume of data
      so that clinicians can manually review it. In this study, we introduce an
      algorithm for detecting and classifying these signals automatically and
      demonstrate the tractability of analyzing a data set of unprecedented size, over
      31,000 channel-hours of intracranial electroencephalographic (iEEG) recordings
      from micro- and macroelectrodes in humans. Using an unsupervised approach that
      does not presuppose a specific number of clusters in the data, we show direct
      evidence for the existence of distinct classes of transient oscillations within
      the 100- to 500-Hz frequency range in a population of nine neocortical epilepsy
      patients and two controls. The number of classes we find, four (three plus one
      putative artifact class), is consistent with prior studies that identify "ripple"
      and "fast ripple" oscillations using human-intensive methods and, additionally,
      identifies a less examined class of mixed-frequency events.

PMID- 20810697
TI  - Ethics for the pediatrician: pediatrician/patient/parent relationships.

PMID- 20810696
TI  - TWEAK-Fn14 interaction enhances plasminogen activator inhibitor 1 and tissue
      factor expression in atherosclerotic plaques and in cultured vascular smooth
      muscle cells.
AB  - AIMS: atherosclerotic plaque development can conclude with a thrombotic acute
      event triggered by plaque rupture/erosion. Tumour necrosis factor-like weak
      inducer of apoptosis (TWEAK) is a member of the tumour necrosis factor
      superfamily that, through its receptor, fibroblast growth factor-inducible 14
      (Fn14), participates in vascular remodelling, increasing vascular inflammatory
      responses and atherosclerotic lesion size in ApoE knockout mice. However, the
      role of the TWEAK-Fn14 axis in thrombosis has not been previously investigated.
      METHODS AND RESULTS: we have examined whether TWEAK regulates expression of
      prothrombotic factors such as tissue factor (TF) and plasminogen activator
      inhibitor 1 (PAI-1) in atherosclerotic plaques as well as in human aortic
      vascular smooth muscle cells (hASMCs) in culture. Expression of TF and PAI-1 was
      colocalized and positively correlated with Fn14 in human carotid atherosclerotic
      plaques. In vitro, TWEAK increased TF and PAI-1 mRNA, protein expression and
      activity in hASMCs. All these effects were reversed using blocking anti-TWEAK
      monoclonal antibody, anti-Fn14 antibody or Fn14 small interfering RNA, indicating
      that TWEAK increased the prothrombotic state through its receptor, Fn14. Finally,
      ApoE(-/-) mice were fed a hyperlipidaemic diet for 10 weeks, then randomized and
      treated with saline (controls), TWEAK (10 microg/kg/day), anti-TWEAK neutralizing
      monoclonal antibody (1000 ug/kg/day), or non-specific immunoglobulin G (1000
      microg/kg/day) daily for 9 days. Systemic TWEAK injection increased TF and PAI-1
      protein expression in the aortic root of ApoE(-/-) mice. Conversely, TWEAK
      blocking antibodies diminished both TF and PAI-1 protein expression compared with
      non-specific immunoglobulin G-treated mice. CONCLUSIONS: our results indicate
      that the TWEAK-Fn14 axis can regulate activation of TF and PAI-1 expression in
      vascular cells. TWEAK-Fn14 may be a therapeutic target in the prothrombotic
      complications associated with atherosclerosis.

PMID- 20810698
TI  - Bullying update: are we making any progress?

PMID- 20810699
TI  - Bone lesions: benign and malignant.

PMID- 20810700
TI  - Developmental milestones: cognitive development.

PMID- 20810701
TI  - Encopresis.

PMID- 20810702
TI  - Focus on diagnosis: cardiac arrhythmias in children.

PMID- 20810703
TI  - Research and statistics: number needed to treat and intention to treat analysis.

PMID- 20810704
TI  - Abnormal head growth.

PMID- 20810705
TI  - Visual diagnosis: multiple joint contractures in a male newborn.

PMID- 20810707
TI  - The price you pay.

PMID- 20810708
TI  - Management of corticosteroid-induced osteoporosis.
AB  - Treatment with corticosteroids can adversely affect bone metabolism. In
      particular, it lowers bone mineral density (BMD) and increases the likelihood of
      fragility fractures, the hallmarks of osteoporosis, hence the term
      'corticosteroid-induced osteoporosis'. Since corticosteroids are used for a wide
      variety of inflammatory conditions, corticosteroid-induced osteoporosis
      represents a substantial disease burden. Here we aim to provide advice on
      prophylaxis and treatment for osteoporosis in adults receiving corticosteroid
      therapy.

PMID- 20810709
TI  - What role for Qlaira in contraception?
AB  - Around 25% of women in the UK aged 16-49 years use oral contraception.1 Annually,
      around 5 million combined oral contraceptive (COC) items are prescribed in
      primary care in England alone, at a cost of over pound40 million. The
      effectiveness of such contraception depends on correct and consistent use of the
      pills and is influenced by unwanted effects that can lead to discontinuation
      (e.g. bleeding irregularities), and by adherence to specified procedures for when
      a pill is missed. Qlaira (Bayer plc) is the first licensed COC in the UK to
      include the oestrogen estradiol valerate (E2V, which is metabolised to
      oestradiol, a natural human hormone) and the progestogen dienogest (DNG). It has
      been marketed as "the first and only COC to deliver...the same oestrogen as
      produced by a woman's body". In theory, it might be less likely than other COCs
      to cause unwanted effects. However, it has a complex dosage regimen, and has its
      own missed-pill guidance which differs substantially from that for other pills.3
      Here we review the effectiveness and place of Qlaira.

PMID- 20810710
TI  - A guide to health economic evaluations.
AB  - Economic evaluations are important in healthcare because they help to inform
      decisions on allocating resources within cash-limited systems. Such evaluations
      are increasingly carried out in appraisals of new treatments, such as those by
      the National Institute for Health and Clinical Excellence (NICE), the Scottish
      Medicines Consortium, and the All Wales Medicines Strategy Group. Healthcare
      professionals and others need a working knowledge of health economic evaluations
      to assess or reach decisions informed by results from such calculations. Here we
      discuss different types of health economic evaluations and how the calculations
      from these analyses are used in decision-making.

PMID- 20810711
TI  - Estrogen receptor-beta prevents cardiac fibrosis.
AB  - Development of cardiac fibrosis portends the transition and deterioration from
      hypertrophy to dilation and heart failure. Here we examined how estrogen blocks
      this important development. Angiotensin II (AngII) and endothelin-1 induce
      cardiac hypertrophy and fibrosis in humans. and we find that these agents
      directly stimulate the transition of the cardiac fibroblast to a myofibroblast.
      AngII and endothelin-1 stimulated TGFbeta1 synthesis in the fibroblast, an
      inducer of fibrosis that signaled via c-jun kinase to Sma- and Mad-related
      protein 3 phosphorylation and nuclear translocation in myofibroblasts. As a
      result, mesenchymal proteins fibronectin and vimentin were produced, as were
      collagens I and III, the major forms found in fibrotic hearts. 17beta-Estradiol
      (E2) or dipropylnitrile, an estrogen receptor (ER)beta agonist, comparably
      blocked all these events, reversed by estrogen receptor (ER)beta small
      interfering RNA. E2 and dipropylnitrile signaling through cAMP and protein kinase
      A prevented myofibroblast formation and blocked activation of c-jun kinase and
      important events of fibrosis. In the hearts of ovariectomized female mice,
      cardiac hypertrophy and fibrosis were induced by AngII infusion and prevented by
      E2 administration to wild type but not ERbeta knockout rodents. Our results
      establish the cardiac fibroblast as an important target for hypertrophic/fibrosis
      inducing peptides the actions of which were mitigated by E2/ERbeta acting in
      these stromal cells.

PMID- 20810713
TI  - Nonadministration of routine probiotics unethical--really?

PMID- 20810712
TI  - Regulation of muscle mass by follistatin and activins.
AB  - Myostatin is a TGF-beta family member that normally acts to limit skeletal muscle
      mass. Follistatin is a myostatin-binding protein that can inhibit myostatin
      activity in vitro and promote muscle growth in vivo. Mice homozygous for a
      mutation in the Fst gene have been shown to die immediately after birth but have
      a reduced amount of muscle tissue, consistent with a role for follistatin in
      regulating myogenesis. Here, we show that Fst mutant mice exhibit
      haploinsufficiency, with muscles of Fst heterozygotes having significantly
      reduced size, a shift toward more oxidative fiber types, an impairment of muscle
      remodeling in response to cardiotoxin-induced injury, and a reduction in tetanic
      force production yet a maintenance of specific force. We show that the effect of
      heterozygous loss of Fst is at least partially retained in a Mstn-null
      background, implying that follistatin normally acts to inhibit other TGF-beta
      family members in addition to myostatin to regulate muscle size. Finally, we
      present genetic evidence suggesting that activin A may be one of the ligands that
      is regulated by follistatin and that functions with myostatin to limit muscle
      mass. These findings potentially have important implications with respect to the
      development of therapeutics targeting this signaling pathway to preserve muscle
      mass and prevent muscle atrophy in a variety of inherited and acquired forms of
      muscle degeneration.

PMID- 20810714
TI  - A cautionary note on instituting probiotics into routine clinical care for
      premature infants.

PMID- 20810715
TI  - Probiotics for preterm infants: confounding features warrant caution.

PMID- 20810722
TI  - Identification of the lipid droplet targeting domain of the Cidea protein.
AB  - Cidea, the cell death-inducing DNA fragmentation factor-alpha-like effector
      (CIDE) domain-containing protein, is targeted to lipid droplets in mouse
      adipocytes, where it inhibits triglyceride hydrolysis and promotes lipid storage.
      In mice, Cidea may prevent lipolysis by binding and shielding lipid droplets from
      lipase association. Here we demonstrate that human Cidea localizes with lipid
      droplets in both adipocyte and nonadipocyte cell lines, and we ascribe specific
      functions to its protein domains. Expression of full-length Cidea in
      undifferentiated 3T3-L1 cells or COS-1 cells increases total cellular
      triglyceride and strikingly alters the morphology of lipid droplets by enhancing
      their size and reducing their number. Remarkably, both lipid droplet binding and
      increased triglyceride accumulation are also elicited by expression of only the
      carboxy-terminal 104 amino acids, indicating this small domain directs lipid
      droplet targeting and triglyceride shielding. However, unlike the full-length
      protein, expression of the carboxy-terminus causes clustering of small lipid
      droplets but not the formation of large droplets, identifying a novel function of
      the N terminus. Furthermore, human Cidea promotes lipid storage via lipolysis
      inhibition, as the expression of human Cidea in fully differentiated 3T3-L1
      adipocytes causes a significant decrease in basal glycerol release. Taken
      together, these data indicate that the carboxy-terminal domain of Cidea directs
      lipid droplet targeting, lipid droplet clustering, and triglyceride accumulation,
      whereas the amino terminal domain is required for Cidea-mediated development of
      enlarged lipid droplets.

PMID- 20810723
TI  - Epstein-Barr Virus SM protein utilizes cellular splicing factor SRp20 to mediate
      alternative splicing.
AB  - Epstein-Barr virus (EBV) SM protein is an essential nuclear protein produced
      during the lytic cycle of EBV replication. SM is an RNA-binding protein with
      multiple mechanisms of action. SM enhances the expression of EBV genes by
      stabilizing mRNA and facilitating nuclear export. SM also influences splicing of
      both EBV and cellular pre-mRNAs. SM modulates splice site selection of the host
      cell STAT1 pre-mRNA, directing utilization of a novel 5' splice site that is used
      only in the presence of SM. SM activates splicing in the manner of SR proteins
      but does not contain the canonical RS domains typical of cellular splicing
      factors. Affinity purification and mass spectrometry of SM complexes from SM
      transfected cells led to the identification of the cellular SR splicing factor
      SRp20 as an SM-interacting protein. The regions of SM and SRp20 required for
      interaction were mapped by in vitro and in vivo assays. The SRp20 interaction was
      shown to be important for the effects of SM on alternative splicing by the use of
      STAT1 splicing assays. Overexpression of SRp20 enhanced SM-mediated alternative
      splicing and knockdown of SRp20 inhibited the SM effect on splicing. These data
      suggest a model whereby SM, a viral protein, recruits and co-opts the function of
      cellular SRp20 in alternative splicing.

PMID- 20810724
TI  - Bioinformatic analysis of the genome of infectious salmon anemia virus associated
      with outbreaks with high mortality in Chile.
AB  - The infectious salmon anemia virus (ISAV), an orthomyxovirus, is the major cause
      of outbreaks of high mortality rates in salmon in Chile. It has been proposed
      that the virulence of ISAV isolates lies mainly in hemagglutinin-esterase and
      fusion glycoproteins. However, based on current information, the contribution of
      other viral genes cannot be ruled out. To study this, we isolated and determined
      the complete coding sequence of two high-prevalence Chilean isolates associated
      with outbreaks of high mortality rates: ISAV752_09 and ISAV901_09. These isolates
      were compared to 15 Norwegian isolates that exhibit differences in their
      virulence. For this purpose, we performed bioinformatic analyses of (i)
      functional domains, (ii) specific mutations, (iii) Bayesian phylogenetics, and
      (iv) structural comparisons between ISAV and influenza virus glycoproteins by
      using molecular modeling. Phylogenetic analysis shows two genogroups for each
      protein, one of them containing the Chilean isolates. The gene sequence of the
      polymerase complex and nucleoprotein indicated that they are closely related to
      homologues from highly pathogenic Norwegian viruses. Notably, seven of the eight
      mutations that are present only in the Chilean isolates are on the polymerase
      complex and nucleoprotein. Structural modeling of hemagglutinin-esterase shows
      patches of variable residues on its surface. Fusion protein modeling shows that
      insertions are flexible regions that could affect proteolytic processing,
      increasing either the accessibility or the number of recognition sites for
      specific proteases. We found antigenic drift processes related to insertion into
      the isolated segment 5 of the ISAV752_09. Our results confirm the European origin
      of Chilean isolates to be the result of reassortments from Norwegian ancestors.

PMID- 20810725
TI  - Widespread horizontal gene transfer from double-stranded RNA viruses to
      eukaryotic nuclear genomes.
AB  - Horizontal gene transfer commonly occurs from cells to viruses but rarely occurs
      from viruses to their host cells, with the exception of retroviruses and some DNA
      viruses. However, extensive sequence similarity searches in public genome
      databases for various organisms showed that the capsid protein and RNA-dependent
      RNA polymerase genes from totiviruses and partitiviruses have widespread homologs
      in the nuclear genomes of eukaryotic organisms, including plants, arthropods,
      fungi, nematodes, and protozoa. PCR amplification and sequencing as well as
      comparative evidence of junction coverage between virus and host sequences
      support the conclusion that these viral homologs are real and occur in eukaryotic
      genomes. Sequence comparison and phylogenetic analysis suggest that these genes
      were likely transferred horizontally from viruses to eukaryotic genomes.
      Furthermore, we present evidence showing that some of the transferred genes are
      conserved and expressed in eukaryotic organisms and suggesting that these viral
      genes are also functional in the recipient genomes. Our findings imply that
      horizontal transfer of double-stranded RNA viral genes is widespread among
      eukaryotes and may give rise to functionally important new genes, thus entailing
      that RNA viruses may play significant roles in the evolution of eukaryotes.

PMID- 20810727
TI  - CD1d, a sentinel molecule bridging innate and adaptive immunity, is downregulated
      by the human papillomavirus (HPV) E5 protein: a possible mechanism for immune
      evasion by HPV.
AB  - CD1d and CD1d-restricted natural killer T (NKT) cells serve as a natural bridge
      between innate and adaptive immune responses to microbes. CD1d downregulation is
      utilized by a variety of microbes to evade immune detection. We demonstrate here
      that CD1d is downregulated in human papillomavirus (HPV)-positive cells in vivo
      and in vitro. CD1d immunoreactivity was strong in HPV-negative normal cervical
      epithelium but absent in HPV16-positive CIN1 and HPV6-positive condyloma lesions.
      We used two cell lines for in vitro assay; one was stably CD1d-transfected cells
      established from an HPV-negative cervical cancer cell line, C33A (C33A/CD1d), and
      the other was normal human vaginal keratinocyte bearing endogenous CD1d (Vag).
      Flow cytometry revealed that cell surface CD1d was downregulated in both
      C33A/CD1d and Vag cells stably transfected with HPV6 E5 and HPV16 E5. Although
      the steady-state levels of CD1d protein decreased in both E5-expressing cell
      lines compared to empty retrovirus-infected cells, CD1d mRNA levels were not
      affected. Confocal microscopy demonstrated that residual CD1d was not trafficked
      to the E5-expressing cell surface but colocalized with E5 near the endoplasmic
      reticulum (ER). In the ER, E5 interacted with calnexin, an ER chaperone known to
      mediate folding of CD1d. CD1d protein levels were rescued by the proteasome
      inhibitor, MG132, indicating a role for proteasome-mediated degradation in HPV
      associated CD1d downregulation. Taken together, our data suggest that E5 targets
      CD1d to the cytosolic proteolytic pathway by inhibiting calnexin-related CD1d
      trafficking. Finally, CD1d-mediated production of interleukin-12 from the
      C33A/CD1d cells was abrogated in both E5-expressing cell lines. Decreased CD1d
      expression in the presence of HPV E5 may help HPV-infected cells evade protective
      immunological surveillance.

PMID- 20810726
TI  - Cytopathogenesis of Sendai virus in well-differentiated primary pediatric
      bronchial epithelial cells.
AB  - Sendai virus (SeV) is a murine respiratory virus of considerable interest as a
      gene therapy or vaccine vector, as it is considered nonpathogenic in humans.
      However, little is known about its interaction with the human respiratory tract.
      To address this, we developed a model of respiratory virus infection based on
      well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs).
      These physiologically authentic cultures are comprised of polarized
      pseudostratified multilayered epithelium containing ciliated, goblet, and basal
      cells and intact tight junctions. To facilitate our studies, we rescued a
      replication-competent recombinant SeV expressing enhanced green fluorescent
      protein (rSeV/eGFP). rSeV/eGFP infected WD-PBECs efficiently and progressively
      and was restricted to ciliated and nonciliated cells, not goblet cells, on the
      apical surface. Considerable cytopathology was evident in the rSeV/eGFP-infected
      cultures postinfection. This manifested itself by ciliostasis, cell sloughing,
      apoptosis, and extensive degeneration of WD-PBEC cultures. Syncytia were also
      evident, along with significant basolateral secretion of proinflammatory
      chemokines, including IP-10, RANTES, tumor necrosis factor (TNF)-related
      apoptosis-inducing ligand (TRAIL), interleukin 6 (IL-6), and IL-8. Such
      deleterious responses are difficult to reconcile with a lack of pathogenesis in
      humans and suggest that caution may be required in exploiting replication
      competent SeV as a vaccine vector. Alternatively, such robust responses might
      constitute appropriate normal host responses to viral infection and be a
      prerequisite for the induction of efficient immune responses.

PMID- 20810728
TI  - VP23R of infectious spleen and kidney necrosis virus mediates formation of virus
      mock basement membrane to provide attaching sites for lymphatic endothelial
      cells.
AB  - Putative open reading frames (ORFs) encoding laminin-like proteins are found in
      all members of the genus Megalocytivirus, family Iridoviridae. This is the first
      study that identified the VP23R protein encoded by ORF23R of the infectious
      spleen and kidney necrosis virus (ISKNV), a member of these genes of
      megalocytiviruses. The VP23R mRNA covering the ISKNV genomic coordinates 19547 to
      22273 was transcribed ahead of the major capsid protein. Immunofluorescence
      analysis demonstrated that VP23R was expressed on the plasma membrane of the
      ISKNV-infected cells and could not be a viral envelope protein. Residues 292 to
      576 of VP23R are homologous to the laminin gamma1III2-6 fragment, which covers
      the nidogen-binding site. An immunoprecipitation assay showed that VP23R could
      interact with nidogen-1, and immunohistochemistry showed that nidogen-1 was
      localized on the outer membrane of the infected cells. Electron microscopy showed
      that a virus-mock basement membrane (VMBM) was formed on the surface of the
      infected cells and a layer of endothelial cells (ECs) was attached to the VMBM.
      The VMBM contained VP23R and nidogen-1 but not collagen IV. The attached ECs were
      identified as lymphatic endothelial cells (LECs), which have unique feature of
      overlapping intercellular junctions and can be stained by immunohistochemistry
      using an antibody against a specific lymphatic marker, Prox-1. Such infection
      signs have never been described in viruses. Elucidating the functions of LECs
      attached to the surface of the infected cells may be useful for studies on the
      pathogenic mechanisms of megalocytiviruses and may also be important for studies
      on lymphangiogenesis and basement membrane functions.

PMID- 20810729
TI  - Immunization with plant-expressed hemagglutinin protects chickens from lethal
      highly pathogenic avian influenza virus H5N1 challenge infection.
AB  - Highly pathogenic avian influenza (HPAI) is a striking disease in susceptible
      poultry, which leads to severe economic losses. Inactivated vaccines are the most
      widely used vaccines in avian influenza virus (AIV) vaccination programs.
      However, these vaccines interfere with the serological detection of wild-type AIV
      infections in immunized populations. The use of vaccines that allow
      differentiation between infected and vaccinated animals (DIVA strategy) would
      stop current stamping-out policies. Therefore, novel vaccination strategies are
      needed to allow improved protection of animals and humans against HPAI virus
      (HPAIV) infection. The presented study analyzed for the first time the
      immunogenic capacity of plant-expressed full-length hemagglutinin (rHA0) of HPAIV
      H5N1 in several vaccine formulations within the highly relevant host species
      chicken. We were able to express plant-expressed rHA0 at high levels and could
      show that, when administered with potent adjuvants, it is highly immunogenic and
      can fully protect chicken against lethal challenge infection. Real-time reverse
      transcription (RT)-PCR and serological tests demonstrated only marginally
      increased virus replication in animals vaccinated with plant-derived rHA0
      compared to animals immunized with an inactivated reference vaccine. In addition,
      the use of plant-expressed rHA0 also allowed an easy serological differentiation
      of vaccinated from AIV-infected animals based on antibodies against the influenza
      virus NP protein.

PMID- 20810730
TI  - Resolving the assembly state of herpes simplex virus during axon transport by
      live-cell imaging.
AB  - Neurotropic herpesviruses depend on long-distance axon transport for the initial
      establishment of latency in peripheral ganglia (retrograde transport) and for
      viral spread in axons to exposed body surfaces following reactivation
      (anterograde transport). Images of neurons infected with herpes simplex virus
      type 1 (HSV-1), acquired using electron microscopy, have led to a debate
      regarding why different types of viral structures are seen in axons and which of
      these particles are relevant to the axon transport process. In this study, we
      applied time-lapse fluorescence microscopy to image HSV-1 virion components
      actively translocating to distal axons in primary neurons and neuronal cell
      lines. Key to these findings, only a small fraction of viral particles were
      engaged in anterograde transport during the egress phase of infection at any
      given time. By selective analysis of the composition of the subpopulation of
      actively transporting capsids, a link between transport of fully assembled HSV-1
      virions and the neuronal secretory pathway was identified. Last, we have
      evaluated the seemingly opposing findings made in previous studies of HSV-1 axon
      transport in fixed cells and demonstrate a limitation to assessing the
      composition of individual HSV-1 particles using antibody detection methods.

PMID- 20810731
TI  - Early selection in Gag by protective HLA alleles contributes to reduced HIV-1
      replication capacity that may be largely compensated for in chronic infection.
AB  - Mutations that allow escape from CD8 T-cell responses are common in HIV-1 and may
      attenuate pathogenesis by reducing viral fitness. While this has been
      demonstrated for individual cases, a systematic investigation of the consequence
      of HLA class I-mediated selection on HIV-1 in vitro replication capacity (RC) has
      not been undertaken. We examined this question by generating recombinant viruses
      expressing plasma HIV-1 RNA-derived Gag-Protease sequences from 66 acute/early
      and 803 chronic untreated subtype B-infected individuals in an NL4-3 background
      and measuring their RCs using a green fluorescent protein (GFP) reporter CD4 T
      cell assay. In acute/early infection, viruses derived from individuals expressing
      the protective alleles HLA-B*57, -B*5801, and/or -B*13 displayed significantly
      lower RCs than did viruses from individuals lacking these alleles (P < 0.05).
      Furthermore, acute/early RC inversely correlated with the presence of HLA-B
      associated Gag polymorphisms (R = -0.27; P = 0.03), suggesting a cumulative
      effect of primary escape mutations on fitness during the first months of
      infection. At the chronic stage of infection, no strong correlations were
      observed between RC and protective HLA-B alleles or with the presence of HLA-B
      associated polymorphisms restricted by protective alleles despite increased
      statistical power to detect these associations. However, RC correlated positively
      with the presence of known compensatory mutations in chronic viruses from B*57
      expressing individuals harboring the Gag T242N mutation (n = 50; R = 0.36; P =
      0.01), suggesting that the rescue of fitness defects occurred through mutations
      at secondary sites. Additional mutations in Gag that may modulate the impact of
      the T242N mutation on RC were identified. A modest inverse correlation was
      observed between RC and CD4 cell count in chronic infection (R = -0.17; P <
      0.0001), suggesting that Gag-Protease RC could increase over the disease course.
      Notably, this association was stronger for individuals who expressed B*57, B*58,
      or B*13 (R = -0.27; P = 0.004). Taken together, these data indicate that certain
      protective HLA alleles contribute to early defects in HIV-1 fitness through the
      selection of detrimental mutations in Gag; however, these effects wane as
      compensatory mutations accumulate in chronic infection. The long-term control of
      HIV-1 in some persons who express protective alleles suggests that early fitness
      hits may provide lasting benefits.

PMID- 20810732
TI  - In vitro selection of highly darunavir-resistant and replication-competent HIV-1
      variants by using a mixture of clinical HIV-1 isolates resistant to multiple
      conventional protease inhibitors.
AB  - We attempted to select HIV-1 variants resistant to darunavir (DRV), which
      potently inhibits the enzymatic activity and dimerization of protease and has a
      high genetic barrier to HIV-1 development of resistance to DRV. We conducted
      selection using a mixture of 8 highly multi-protease inhibitor (PI)-resistant,
      DRV-susceptible clinical HIV-1 variants (HIV-1(MIX)) containing 9 to 14 PI
      resistance-associated amino acid substitutions in protease. HIV-1(MIX) became
      highly resistant to DRV, with a 50% effective concentration (EC(50)) ~333-fold
      greater than that against HIV-1(NL4-3). HIV-1(MIX) at passage 51 (HIV
      1(MIX(P51))) replicated well in the presence of 5 MUM DRV and contained 14
      mutations. HIV-1(MIX(P51)) was highly resistant to amprenavir, indinavir,
      nelfinavir, ritonavir, lopinavir, and atazanavir and moderately resistant to
      saquinavir and tipranavir. HIV-1(MIX(P51)) had a resemblance with HIV-1(C) of the
      HIV-1(MIX) population, and selection using HIV-1(C) was also performed; however,
      its DRV resistance acquisition was substantially delayed. The H219Q and I223V
      substitutions in Gag, lacking in HIV-1(C(P51)), likely contributed to conferring
      a replication advantage on HIV-1(MIX(P51)) by reducing intravirion cyclophilin A
      content. HIV-1(MIX(P51)) apparently acquired the substitutions from another HIV-1
      strain(s) of HIV-1(MIX) through possible homologous recombination. The present
      data suggest that the use of multiple drug-resistant HIV-1 isolates is of utility
      in selecting drug-resistant variants and that DRV would not easily permit HIV-1
      to develop significant resistance; however, HIV-1 can develop high levels of DRV
      resistance when a variety of PI-resistant HIV-1 strains are generated, as seen in
      patients experiencing sequential PI failure, and ensuing homologous recombination
      takes place. HIV-1(MIX(P51)) should be useful in elucidating the mechanisms of
      HIV-1 resistance to DRV and related agents.

PMID- 20810733
TI  - A live attenuated H7N7 candidate vaccine virus induces neutralizing antibody that
      confers protection from challenge in mice, ferrets, and monkeys.
AB  - A live attenuated H7N7 candidate vaccine virus was generated by reverse genetics
      using the modified hemagglutinin (HA) and neuraminidase (NA) genes of highly
      pathogenic (HP) A/Netherlands/219/03 (NL/03) (H7N7) wild-type (wt) virus and the
      six internal protein genes of the cold-adapted (ca) A/Ann Arbor/6/60 ca (AA ca)
      (H2N2) virus. The reassortant H7N7 NL/03 ca vaccine virus was temperature
      sensitive and attenuated in mice, ferrets, and African green monkeys (AGMs).
      Intranasal (i.n.) administration of a single dose of the H7N7 NL/03 ca vaccine
      virus fully protected mice from lethal challenge with homologous and heterologous
      H7 viruses from Eurasian and North American lineages. Two doses of the H7N7 NL/03
      ca vaccine induced neutralizing antibodies in serum and provided complete
      protection from pulmonary replication of homologous and heterologous wild-type H7
      challenge viruses in mice and ferrets. One dose of the H7N7 NL/03 ca vaccine
      elicited an antibody response in one of three AGMs that was completely protected
      from pulmonary replication of the homologous wild-type H7 challenge virus. The
      contribution of CD8(+) and/or CD4(+) T cells to the vaccine-induced protection of
      mice was evaluated by T-cell depletion; T lymphocytes were not essential for the
      vaccine-induced protection from lethal challenge with H7 wt viruses.
      Additionally, passively transferred neutralizing antibody induced by the H7N7
      NL/03 ca virus protected mice from lethality following challenge with H7 wt
      viruses. The safety, immunogenicity, and efficacy of the H7N7 NL/03 ca vaccine
      virus in mice, ferrets, and AGMs support the evaluation of this vaccine virus in
      phase I clinical trials.

PMID- 20810734
TI  - Andes virus disrupts the endothelial cell barrier by induction of vascular
      endothelial growth factor and downregulation of VE-cadherin.
AB  - Hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome
      (HFRS) are severe diseases associated with hantavirus infection. High levels of
      virus replication occur in microvascular endothelial cells but without a virus
      induced cytopathic effect. However, virus infection results in microvascular
      leakage, which is the hallmark of these diseases. VE-cadherin is a major
      component of adherens junctions, and its interaction with the vascular
      endothelial growth factor (VEGF) receptor, VEGF-R2, is important for maintaining
      the integrity of the endothelial barrier. Here we report that increased secreted
      VEGF and concomitant decreased VE-cadherin are seen at early times postinfection
      of human primary lung endothelial cells with an HPS-associated hantavirus, Andes
      virus. Furthermore, active virus replication results in increased permeability
      and loss of the integrity of the endothelial cell barrier. VEGF binding to VEGF
      R2 is known to result in dissociation of VEGF-R2 from VE-cadherin and in VE
      cadherin activation, internalization, and degradation. Consistent with this, we
      showed that an antibody which blocks VEGF-R2 activation resulted in inhibition of
      the Andes virus-induced VE-cadherin reduction. These data implicate virus
      induction of VEGF and reduction in VE-cadherin in the endothelial cell
      permeability seen in HPS and suggest potential immunotherapeutic targets for the
      treatment of the disease.

PMID- 20810735
TI  - Hepatitis C virus infection impairs IRF-7 translocation and Alpha interferon
      synthesis in immortalized human hepatocytes.
AB  - Hepatitis C virus (HCV) establishes chronic infection in a significant number of
      infected humans, although the mechanisms for chronicity remain largely unknown.
      We have previously shown that HCV infection in immortalized human hepatocytes
      (IHH) induces beta interferon (IFN-beta) expression (T. Kanda, R. Steele, R. Ray,
      and R. B. Ray, J. Virol. 81:12375-12381, 2007). However, the regulation of the
      downstream signaling pathway for IFN-alpha production by HCV is not clearly
      understood. In this study, the regulation of the IFN signaling pathway following
      HCV genotype 1a (clone H77) or genotype 2a (clone JFH1) infection of IHH was
      examined. HCV infection upregulated expression of total STAT1 but failed to
      induce phosphorylation and efficient nuclear translocation. Subsequent study
      revealed that HCV infection induces IFN-stimulated response element activation,
      as evidenced by upregulation of 2',5'-oligoadenylate synthetase 1. However,
      nuclear translocation of IRF-7 was impaired following HCV infection. In HCV
      infected IHH, IFN-alpha expression initially increased (up to 24 h) and then
      decreased at later time points, and IFN-alpha-inducible protein 27 was not
      induced. Interestingly, HCV infection blocked IRF-7 nuclear translocation upon
      poly(I-C) or IFN-alpha treatment of IHH. Together, our data suggest that HCV
      infection enhances STAT1 expression but impairs nuclear translocation of IRF-7
      and its downstream molecules. These impairments in the IFN-alpha signaling
      pathway may, in part, be responsible for establishment of chronic HCV infection.

PMID- 20810737
TI  - Cytotoxicity of ORF3 proteins from a nonpathogenic and a pathogenic porcine
      circovirus.
AB  - Porcine circovirus type 2 (PCV2) infection is associated with significant and
      serious swine diseases worldwide, while PCV1 appears to be a nonpathogenic virus.
      Previous studies demonstrated that the ORF3 protein of PCV2 (PCV2ORF3) was
      involved in PCV2 pathogenesis via its proapoptotic capability (J. Liu, I. Chen,
      Q. Du, H. Chua, and J. Kwang, J. Virol. 80:5065-5073, 2006). If PCV2ORF3-induced
      apoptosis is a determinant of virulence, PCV1ORF3 is hypothesized to lack this
      ability. The properties of PCV1 and PCV2 ORF3, expressed as fusion proteins to an
      enhanced green fluorescent protein (eGFP), were characterized with regard to
      their ability to cause cellular morphological changes, detachment, death, and
      apoptosis. PCV1ORF3 significantly induced more apoptotic cell death and was toxic
      to more different cell types than PCV2ORF3 was. PCV1ORF3-associated cell death
      was caspase dependent. PCV1ORF3 also induced poly(ADP-ribose) polymerase 1 (PARP)
      cleavage; however, whether PARP was involved in cell death requires further
      studies. Truncation of PCV1 and elongation of PCV2 ORF3 proteins revealed that
      the first 104 amino acids contain a domain capable of inducing cell death,
      whereas the C terminus of PCV1ORF3 contains a domain possibly responsible for
      enhancing cell death. These results suggest that the pathogenicity of PCV2 for
      pigs is either not determined or not solely determined by the ORF3 protein.

PMID- 20810736
TI  - Effective formation of the segregation-competent complex determines successful
      partitioning of the bovine papillomavirus genome during cell division.
AB  - Effective segregation of the bovine papillomavirus type 1 (BPV1), Epstein-Barr
      virus (EBV), and Kaposi's sarcoma-associated human herpesvirus type 8 (KSHV)
      genomes into daughter cells is mediated by a single viral protein that tethers
      viral genomes to host mitotic chromosomes. The linker proteins that mediate BPV1,
      EBV, and KSHV segregation are E2, LANA1, and EBNA1, respectively. The N-terminal
      transactivation domain of BPV1 E2 is responsible for chromatin attachment and
      subsequent viral genome segregation. Because E2 transcriptional activation and
      chromatin attachment functions are not mutually exclusive, we aimed to determine
      the requirement of these activities during segregation by analyzing chimeric E2
      proteins. This approach allowed us to separate the two activities. Our data
      showed that attachment of the segregation protein to chromatin is not sufficient
      for proper segregation. Rather, formation of a segregation-competent complex
      which carries multiple copies of the segregation protein is required.
      Complementation studies of E2 functional domains indicated that chromatin
      attachment and transactivation functions must act in concert to ensure proper
      plasmid segregation. These data indicate that there are specific interactions
      between linker molecules and transcription factors/complexes that greatly
      increase segregation-competent complex formation. We also showed, using hybrid E2
      molecules, that restored segregation function does not involve interactions with
      Brd4.

PMID- 20810740
TI  - Improvement of visual search after audiovisual exploration training in hemianopic
      patients.
AB  - OBJECTIVE: A variety of rehabilitation strategies have been tried in patients
      with chronic hemianopia and quadrantanopia. The authors compared 2 approaches of
      blind field exploration in those with recent onset of disease. METHODS: A total
      of 20 patients with visual field defects were studied between 3 and 24 weeks
      primarily after stroke. Patients were randomly assigned to separate groups
      performing either audiovisual stimulation training or a visual stimulation
      training (20 sessions, each lasting 30 minutes). Patients were evaluated before
      and after the training with visual exploration tests for reading and object
      search; eye movements were analyzed with electro-oculography, and a questionnaire
      was completed by an occupational therapist about impairment in daily life
      activities. RESULTS: Both groups improved their performance after compensatory
      eye movement training. Comparisons between the 2 forms of training revealed a
      significantly greater improvement for all outcome variables for the audiovisual
      group. In particular audiovisual stimulation significantly increased the number
      and amplitude of saccades. CONCLUSIONS: Multimodal audiovisual exploration
      training appears to be more effective than exploration training alone and may
      improve function beyond spontaneous recovery soon after ischemia of the occipital
      lobe.

PMID- 20810738
TI  - Conserved and variable features of Gag structure and arrangement in immature
      retrovirus particles.
AB  - The assembly of retroviruses is driven by oligomerization of the Gag polyprotein.
      We have used cryo-electron tomography together with subtomogram averaging to
      describe the three-dimensional structure of in vitro-assembled Gag particles from
      human immunodeficiency virus, Mason-Pfizer monkey virus, and Rous sarcoma virus.
      These represent three different retroviral genera: the lentiviruses,
      betaretroviruses and alpharetroviruses. Comparison of the three structures
      reveals the features of the supramolecular organization of Gag that are conserved
      between genera and therefore reflect general principles of Gag-Gag interactions
      and the features that are specific to certain genera. All three Gag proteins
      assemble to form approximately spherical hexameric lattices with irregular
      defects. In all three genera, the N-terminal domain of CA is arranged in
      hexameric rings around large holes. Where the rings meet, 2-fold densities,
      assigned to the C-terminal domain of CA, extend between adjacent rings, and link
      together at the 6-fold symmetry axis with a density, which extends toward the
      center of the particle into the nucleic acid layer. Although this general
      arrangement is conserved, differences can be seen throughout the CA and spacer
      peptide regions. These differences can be related to sequence differences among
      the genera. We conclude that the arrangement of the structural domains of CA is
      well conserved across genera, whereas the relationship between CA, the spacer
      peptide region, and the nucleic acid is more specific to each genus.

PMID- 20810741
TI  - Floral ontogeny of Annonaceae: evidence for high variability in floral form.
AB  - BACKGROUND AND AIMS: Annonaceae are one of the largest families of Magnoliales.
      This study investigates the comparative floral development of 15 species to
      understand the basis for evolutionary changes in the perianth, androecium and
      carpels and to provide additional characters for phylogenetic investigation.
      METHODS: Floral ontogeny of 15 species from 12 genera is examined and described
      using scanning electron microscopy. KEY RESULTS: Initiation of the three perianth
      whorls is either helical or unidirectional. Merism is mostly trimerous,
      occasionally tetramerous and the members of the inner perianth whorl may be
      missing or are in double position. The androecium and the gynoecium were found to
      be variable in organ numbers (from highly polymerous to a fixed number, six in
      the androecium and one or two in the gynoecium). Initiation of the androecium
      starts invariably with three pairs of stamen primordia along the sides of the
      hexagonal floral apex. Although inner staminodes were not observed, they were
      reported in other genera and other families of Magnoliales, except Magnoliaceae
      and Myristicaceae. Initiation of further organs is centripetal. Androecia with
      relatively low stamen numbers have a whorled phyllotaxis throughout, while
      phyllotaxis becomes irregular with higher stamen numbers. The limits between
      stamens and carpels are unstable and carpels continue the sequence of stamens
      with a similar variability. CONCLUSIONS: It was found that merism of flowers is
      often variable in some species with fluctuations between trimery and tetramery.
      Doubling of inner perianth parts is caused by (unequal) splitting of primordia,
      contrary to the androecium, and is independent of changes of merism. Derived
      features, such as a variable merism, absence of the inner perianth and inner
      staminodes, fixed numbers of stamen and carpels, and capitate or elongate styles
      are distributed in different clades and evolved independently. The evolution of
      the androecium is discussed in the context of basal angiosperms: paired outer
      stamens are the consequence of the transition between the larger perianth parts
      and much smaller stamens, and not the result of splitting. An increase in stamen
      number is correlated with their smaller size at initiation, while limits between
      stamens and carpels are unclear with easy transitions of one organ type into
      another in some genera, or the complete replacement of carpels by stamens in
      unisexual flowers.

PMID- 20810742
TI  - Characterization of a rice variety with high hydraulic conductance and
      identification of the chromosome region responsible using chromosome segment
      substitution lines.
AB  - BACKGROUND AND AIMS: The rate of photosynthesis in paddy rice often decreases at
      noon on sunny days because of water stress, even under submerged conditions.
      Maintenance of higher rates of photosynthesis during the day might improve both
      yield and dry matter production in paddy rice. A high-yielding indica variety,
      'Habataki', maintains a high rate of leaf photosynthesis during the daytime
      because of the higher hydraulic conductance from roots to leaves than in the
      standard japonica variety 'Sasanishiki'. This research was conducted to
      characterize the trait responsible for the higher hydraulic conductance in
      'Habataki' and identified a chromosome region for the high hydraulic conductance.
      METHODS: Hydraulic conductance to passive water transport and to osmotic water
      transport was determined for plants under intense transpiration and for plants
      without transpiration, respectively. The varietal difference in hydraulic
      conductance was examined with respect to root surface area and hydraulic
      conductivity (hydraulic conductance per root surface area, L(p)). To identify the
      chromosome region responsible for higher hydraulic conductance, chromosome
      segment substitution lines (CSSLs) derived from a cross between 'Sasanishiki' and
      'Habataki' were used. KEY RESULTS: The significantly higher hydraulic conductance
      resulted from the larger root surface area not from L(p) in 'Habataki'. A
      chromosome region associated with the elevated hydraulic conductance was detected
      between RM3916 and RM2431 on the long arm of chromosome 4. The CSSL, in which
      this region was substituted with the 'Habataki' chromosome segment in the
      'Sasanishiki' background, had a larger root mass than 'Sasanishiki'. CONCLUSIONS:
      The trait for increasing plant hydraulic conductance and, therefore, maintaining
      the higher rate of leaf photosynthesis under the conditions of intense
      transpiration in 'Habataki' was identified, and it was estimated that there is at
      least one chromosome region for the trait located on chromosome 4.

PMID- 20810743
TI  - Arbuscular mycorrhizal fungi restore normal growth in a white poplar clone grown
      on heavy metal-contaminated soil, and this is associated with upregulation of
      foliar metallothionein and polyamine biosynthetic gene expression.
AB  - BACKGROUND AND AIMS: It is increasingly evident that plant tolerance to stress is
      improved by mycorrhiza. Thus, suitable plant-fungus combinations may also
      contribute to the success of phytoremediation of heavy metal (HM)-polluted soil.
      Metallothioneins (MTs) and polyamines (PAs) are implicated in the response to HM
      stress in several plant species, but whether the response is modulated by
      arbuscular mycorrhizal fungi (AMF) remains to be clarified. The aim of the
      present study was to check whether colonization by AMF could modify growth, metal
      uptake/translocation, and MT and PA gene expression levels in white poplar
      cuttings grown on HM-contaminated soil, and to compare this with plants grown on
      non-contaminated soil. METHODS: In this greenhouse study, plants of a Populus
      alba clone were pre-inoculated, or not, with either Glomus mosseae or G.
      intraradices and then grown in pots containing either soil collected from a
      multimetal- (Cu and Zn) polluted site or non-polluted soil. The expression of MT
      and PA biosynthetic genes was analysed in leaves using quantitative reverse
      transcription-PCR. Free and conjugated foliar PA concentrations were determined
      in parallel. RESULTS: On polluted soil, AMF restored plant biomass despite higher
      Cu and Zn accumulation in plant organs, especially roots. Inoculation with the
      AMF caused an overall induction of PaMT1, PaMT2, PaMT3, PaSPDS1, PaSPDS2 and
      PaADC gene expression, together with increased free and conjugated PA levels, in
      plants grown on polluted soil, but not in those grown on non-polluted soil.
      CONCLUSIONS: Mycorrhizal plants of P. alba clone AL35 exhibit increased capacity
      for stabilization of soil HMs, together with improved growth. Their enhanced
      stress tolerance may derive from the transcriptional upregulation of several
      stress-related genes, and the protective role of PAs.

PMID- 20810744
TI  - Distribution of Far-Eastern tick-borne encephalitis virus subtype strains in the
      former Soviet Union.
AB  - European and Asian viruses within the tick-borne encephalitis flavivirus complex
      are known to show temporal, spatial and phylogenetic relationships that imply a
      clinal pattern of evolution. However, the isolation of recognized Far-Eastern
      tick-borne encephalitis virus (TBEV) strains in the European region of the former
      Soviet Union (SU), i.e. thousands of kilometres west of the region in which they
      are considered endemic, appears to contradict this concept. Here, we present a
      parsimonious explanation for this apparent anomaly based on analysis of the dates
      and regions in which these non-endemic strains were isolated, together with their
      phylogenetic relationships and the records of redistribution of animals under the
      All-Union programme for acclimatization of game animals within the former SU. Our
      evidence supports the concept that the anomalous distribution of Far-Eastern TBEV
      strains in Europe and Siberia arose primarily as the result of the large-scale
      westward redistribution of game animals for economic purposes.

PMID- 20810745
TI  - Removal of transposon target sites from the Autographa californica multiple
      nucleopolyhedrovirus fp25k gene delays, but does not prevent, accumulation of the
      few polyhedra phenotype.
AB  - Low-cost, large-scale production of the baculovirus Autographa californica
      multiple nucleopolyhedrovirus (AcMNPV) using continuous insect cell culture is
      seriously hindered by the accumulation of AcMNPV mutants. Specifically, few
      polyhedra (FP) mutants, with a reduced yield of occluded virus (polyhedra) and
      decreased infectivity, usually accumulate upon passaging in cell culture. FP
      mutations result from transposon insertions in the baculovirus fp25k gene,
      leading to significantly reduced levels of FP25K protein synthesis. This study
      evaluated the effects of removing the transposon insertion sites from the wild
      type baculovirus fp25k gene; the mutated virus was denoted Ac-FPm. Specifically,
      this study involved a detailed comparison of wild-type (WT) AcMNPV and Ac-FPm
      with regard to the proportion of cells having polyhedra, number of polyhedra per
      cell, the fraction of empty polyhedra, number of occlusion-derived viruses per
      polyhedron, number of nucleocapsids in the nuclei, FP25K protein synthesis and
      genetic analysis of the fp25k gene. Removal of TTAA transposon insertion sites
      from the fp25k gene stabilized FP25K protein synthesis and delayed the appearance
      of the FP phenotype from passage 5 to passage 10. Electron micrographs revealed
      that more virus particles were found inside the nuclei of cells infected with Ac
      FPm than in the nuclei of cells infected with WT AcMNPV (at passage 10).
      Abnormalities, however, were observed in envelopment of nucleocapsids and virus
      particle occlusion within Ac-FPm polyhedra. Thus, the FP phenotype appeared in
      spite of continued FP25K protein synthesis, suggesting that mechanisms other than
      fp25k gene disruption can lead to the FP phenotype.

PMID- 20810746
TI  - C-C chemokine receptor type 5 (CCR5) utilization of transmitted and early founder
      human immunodeficiency virus type 1 envelopes and sensitivity to small-molecule
      CCR5 inhibitors.
AB  - The envelope glycoprotein (Env) of human immunodeficiency virus is key to viral
      entry of susceptible target cells and is therefore a major target for the design
      of vaccines and antiviral drugs. C-C chemokine receptor type 5 (CCR5)-using (R5)
      Env is the predominant phenotype associated with early transmission and acute
      infection. This study investigated the mechanism of CCR5 use and the sensitivity
      to CCR5 inhibitors of a panel of transmitted or early founder (T/F) Envs. The
      data showed that the majority of T/F Envs used CCR5 and that many also used CCR3,
      although less efficiently. Despite a similar ability to use wild-type CCR5,
      individual Envs differed significantly in their sensitivity to the CCR5
      inhibitors maraviroc, CMPD-167 and SCH-412147. Inhibitor mapping experiments
      demonstrated that maraviroc, CMPD-167 and SCH-412147 interfered with the binding
      of CCR5 mAb to the C-terminal half of the second extracellular loop 2 of CCR5.
      Interestingly, Envs resistant to maraviroc, CMPD167 and SCH-412147 remained
      sensitive to TAK-779. Further studies indicated that the sensitivity of Envs to
      CCR5 inhibitors correlated with the molecular anatomy of CCR5 use, revealing that
      the inhibitor-sensitive Envs barely used the CCR5&emsp14;N terminus, whereas
      resistant Envs showed a marked increase in its use. Taken together, these
      findings demonstrate that T/F R5 Envs are heterogeneous with respect to the
      mechanisms of CCR5 utilization. These data may have implications for therapeutic
      and prophylactic use of CCR5-based antiretrovirals.

PMID- 20810747
TI  - High-resolution epitope mapping for monoclonal antibodies to the structural
      protein Erns of classical swine fever virus using peptide array and random
      peptide phage display approaches.
AB  - The structural glycoprotein E(rns) (an envelope protein with RNase activity) of
      classical swine fever virus (CSFV) is not well characterized with respect to its
      antigenic structure and organization. Here, we investigated the antigenic sites
      on E(rns) by raising mAbs against the Escherichia coli expressed E(rns) of CSFV
      strain Alfort/187 and defined the B-cell epitopes recognized by these antibodies.
      Eighteen mAbs to E(rns) were identified and they were classified as either
      immunoglobulin subclass G1 or G2b. Using an array of overlapping 12-mer peptides,
      spanning aa 27-227 of E(rns), the epitopes for 12 mAbs were mapped to a high
      resolution of six to eight residues, which cluster in five discrete locations,
      13GIWPEKIC38 (group I), 65NYTCCKLQ72 (group II), 127QARNRPTT134 (group III),
      145SFAGTVIE152 (group IV) and 161VEDILY166 (group V). Two mAbs recognize two or
      more antigenic determinants, including the group II epitope. The epitopes for
      four other mAbs could not be mapped using the overlapping 12-mer peptides. Random
      peptide phage display with one mAb from each of all the groups except group V
      further identified some conserved residues that may be critical for binding
      antibodies, i.e. Trp33 in the epitope of group I, Leu71 in the epitope of group
      II, Gln127 and Apn130 in the epitope of group III, and Ser145 and Gly148 in the
      epitope of group IV. This study has provided new insights into the structure and
      organization of epitopes on the CSFV E(rns) and valuable epitope information for
      the rational design of vaccines, drugs and diagnostic immunoassays for CSFV.

PMID- 20810748
TI  - Delineating the role of CD4+ T cells in the activation of human cytomegalovirus
      specific immune responses following immunization with Ad-gBCMVpoly vaccine:
      implications for vaccination of immunocompromised individuals.
AB  - Reconstitution of the virus-specific CD8(+) T-cell response is crucial for the
      prevention of human cytomegalovirus (CMV)-associated pathogenesis in transplant
      patients and human immunodeficiency virus-infected individuals. Although adoptive
      T-cell immunotherapy has been used successfully in various clinical settings,
      prophylactic vaccination remains the most amenable strategy to prevent CMV
      disease. However, vaccination in clinical settings where the host is severely
      immunocompromised due to the loss of CD4(+) T cells remains a significant
      challenge. This study investigated the efficacy of a chimeric CMV vaccine in a
      model setting that allowed studies on the generation of CD8(+) T-cell memory
      responses in a transient CD4(+) T-cell-deficient setting similar to that seen in
      immunocompromised patients. Immunization with an adenoviral CMV vaccine under
      transient helpless (complete CD4(+) T-cell depletion) or help-deficient (partial
      CD4(+) T-cell depletion) conditions demonstrated that induction of the effector
      CD8(+) T-cell and humoral responses was almost completely eliminated under
      helpless conditions, and was gradually regained with the recovery of CD4(+) T
      cells. However, this response failed to protect the host from viral infection,
      suggesting that lack of CD4(+) T cells during vaccination can significantly
      impair the priming and maturation of CMV-specific immune responses. Furthermore,
      although the induction of CMV-specific immune responses was also significantly
      reduced in a help-deficient environment, these primed effector cells could mature
      normally and generate long-term polyfunctional memory responses capable of
      restricting virus replication in vivo. These results highlight the importance of
      monitoring CD4(+) T-cell numbers before vaccination for the successful
      implementation of a CMV vaccine in an immunocompromised setting.

PMID- 20810750
TI  - Bovine parvovirus uses clathrin-mediated endocytosis for cell entry.
AB  - Entry events of bovine parvovirus (BPV) were studied. Transmission electron
      micrographs of infected cells showed virus particles in cytoplasmic vesicles.
      Chemical inhibitors that block certain aspects of the cellular machinery were
      employed to assess viral dependency upon those cellular processes.
      Chlorpromazine, ammonium chloride, chloroquine and bafilamicin A1 were used to
      inhibit acidification of endosomes and clathrin-associated endocytosis. Nystatin
      was used as an inhibitor of the caveolae pathway. Cytochalasin D and ML-7 were
      used to inhibit actin and myosin functions, respectively. Nocodazole and
      colchicine were employed to inhibit microtubule activity. Virus entry was
      assessed by measuring viral transcription using real-time PCR, synthesis of
      capsid protein and assembly of infectious progeny virus in the presence of
      inhibitor blockage. The results indicated that BPV entry into embryonic bovine
      trachael cells utilizes endocytosis in clathrin-coated vesicles, is dependent
      upon acidification, and appears to be associated with actin and microtubule
      dependency. Evidence for viral entry through caveolae was not obtained. These
      findings provide a fuller understanding of the early cell-entry events of the
      replication cycle for members of the genus Bocavirus.

PMID- 20810749
TI  - Phosphoinositide 3 kinase signalling may affect multiple steps during herpes
      simplex virus type-1 entry.
AB  - Early interactions of herpes simplex virus type-1 (HSV-1) with cells lead to
      cytoskeletal changes facilitating filopodia formation and membrane fusion. Here,
      we demonstrate that phosphoinositide 3 kinase (PI3K) signalling may affect
      multiple steps during HSV-1 entry. An inhibitor of PI3K (LY294002) blocked HSV-1
      entry and the blockage was cell-type- and gD receptor-independent. Entry
      inhibition was also observed with primary cultures of the human corneal
      fibroblasts and unrelated beta- and gamma-herpesviruses. Immunofluorescence
      analysis demonstrated that LY294002 negatively affected HSV-1-induced filopodia
      formation. Similar effects of the inhibitor were seen on HSV-1 glycoprotein
      induced cell-to-cell fusion. Cells expressing HSV-1 glycoproteins (gB, gD, gH and
      gL) showed significantly less fusion with target cells in the presence of the
      inhibitor. Expression of a dominant-negative PI3K mutant negatively affected both
      entry and fusion. We also show that inhibition of PI3K signalling also affected
      RhoA activation required for HSV-1 entry into certain cell types.

PMID- 20810751
TI  - Cardiovascular disease.

PMID- 20810752
TI  - Oncology.

PMID- 20810753
TI  - General nuclear medicine.

PMID- 20810754
TI  - Neuroscience.

PMID- 20810756
TI  - Fulfilling a need for evidence-based medicine.

PMID- 20810757
TI  - A new pyrimidine-specific reporter gene: a mutated human deoxycytidine kinase
      suitable for PET during treatment with acycloguanosine-based cytotoxic drugs.
AB  - In this article, we describe a series of new human-derived reporter genes based
      on human deoxycytidine kinase (dCK) suitable for clinical PET. METHODS: Native
      dCK and its mutant reporter genes were tested in vitro and in vivo for their
      phosphorylation of pyrimidine- and acycloguanosine-based radiotracers including
      2'-deoxy-2'-fluoroarabinofuranosylcytosine, 2'-fluoro-2'-deoxyarabinofuranosyl-5
      ethyluracil (FEAU), penciclovir, and 9-[4-fluoro-3-(hydroxymethyl)butyl]guanine
      (FHBG) and clinically applied antiviral and anticancer drugs. RESULTS: Cells
      transduced with dCK mutant reporter genes showed high in vitro and in vivo uptake
      of pyrimidine-based radiopharmaceuticals ((18)F-FEAU) comparable to that of
      herpes simplex virus type-1 thymidine kinase (HSV1-tk)-transduced cells. These
      mutants did not phosphorylate acycloguanosine-based radiotracers ((18)F-FHBG) or
      antiviral drugs (ganciclovir). Furthermore, the mutants displayed suicidal
      activation of clinically used pyrimidine-based prodrugs (cytarabine,
      gemcitabine). CONCLUSION: The mutants of human dCK can be used as pyrimidine
      specific PET reporter genes for imaging with (18)F-FEAU during treatment with
      acycloguanosine-based antiviral drugs. Additionally, the prosuicidal activity of
      these reporters with pyrimidine-based analogs will allow for the safe elimination
      of transduced cells.

PMID- 20810758
TI  - Target-specific PET probes for neurodegenerative disorders related to dementia.
AB  - Dementia is a highly prevalent problem causing considerable disability and
      mortality and exacting great costs to individuals, their families, and society.
      The 4 most common neurodegenerative disorders that cause dementia-Alzheimer
      disease, frontotemporal dementia, dementia with Lewy bodies, and dementia in
      Parkinson disease-have different underlying etiologies and pathogenetic
      mechanisms. There is a great need for early diagnostic markers; functional brain
      imaging may therefore assist in the detection and differential diagnosis of
      dementia due to neurodegenerative diseases. Functional imaging such as PET allows
      in vivo imaging of functional brain activity indicating cerebral blood flow and
      cerebral glucose metabolism, and PET allows imaging of neurotransmitter activity,
      including that of the cholinergic, dopaminergic, and serotonergic systems. New
      PET neuroimaging tracers are being developed for detecting pathologic parameters
      such as amyloid plaque and microglial activity. The development of molecular
      imaging is important for early diagnosis of dementia, selection of patients for
      therapies, and evaluation of therapies.

PMID- 20810759
TI  - Toward implementing an MRI-based PET attenuation-correction method for neurologic
      studies on the MR-PET brain prototype.
AB  - Several factors have to be considered for implementing an accurate attenuation
      correction (AC) method in a combined MR-PET scanner. In this work, some of these
      challenges were investigated, and an AC method based entirely on the MRI data
      obtained with a single dedicated sequence was developed and used for neurologic
      studies performed with the MR-PET human brain scanner prototype. METHODS: The
      focus was on the problem of bone-air segmentation, selection of the linear
      attenuation coefficient for bone, and positioning of the radiofrequency coil. The
      impact of these factors on PET data quantification was studied in simulations and
      experimental measurements performed on the combined MR-PET scanner. A novel dual
      echo ultrashort echo time (DUTE) MRI sequence was proposed for head imaging.
      Simultaneous MR-PET data were acquired, and the PET images reconstructed using
      the proposed DUTE MRI-based AC method were compared with the PET images that had
      been reconstructed using a CT-based AC method. RESULTS: Our data suggest that
      incorrectly accounting for the bone tissue attenuation can lead to large
      underestimations (>20%) of the radiotracer concentration in the cortex. Assigning
      a linear attenuation coefficient of 0.143 or 0.151 cm(-1) to bone tissue appears
      to give the best trade-off between bias and variability in the resulting images.
      Not identifying the internal air cavities introduces large overestimations (>20%)
      in adjacent structures. On the basis of these results, the segmented CT AC method
      was established as the silver standard for the segmented MRI-based AC method. For
      an integrated MR-PET scanner, in particular, ignoring the radiofrequency coil
      attenuation can cause large underestimations (i.e., <or=50%) in the reconstructed
      images. Furthermore, the coil location in the PET field of view has to be
      accurately known. High-quality bone-air segmentation can be performed using the
      DUTE data. The PET images obtained using the DUTE MRI- and CT-based AC methods
      compare favorably in most of the brain structures. CONCLUSION: A DUTE MRI-based
      AC method considering all these factors was implemented. Preliminary results
      suggest that this method could potentially be as accurate as the segmented CT
      method and could be used for quantitative neurologic MR-PET studies.

PMID- 20810760
TI  - Carbon monoxide inhalation decreased lung injury via anti-inflammatory and anti
      apoptotic effects in brain death rats.
AB  - Brain death (BD) induces acute lung injury and makes donor lungs unfit for
      transplantation. Carbon monoxide (CO) inhalation at 50-500 ppm exerts anti
      inflammatory and anti-apoptosis effects in several lung injury models. We
      examined whether CO inhalation would show favorable effects on lung injury in BD
      rats. BD rats inhaled 250 ppm CO for two hours. Inhalation decreased the severity
      of lung injury, as checked by histological examination. CO treatment reversed
      aggravation in PaO(2)/FiO(2), base excess and pH of BD rats. CO inhalation
      downregulated the pro-inflammatory cytokines (tumor necrosis factor-alpha,
      interleukin-6), and inhibited activity of myeloperoxidase in lung tissue.
      Inhalation significantly decreased cell apoptosis of lungs, and inhibited mRNA
      expression of intercellular adhesion molecule-1 and caspase-3 in the lungs.
      Further, the inhalation activated phosphorylation of p38 expression and inhibited
      phosphorylation of extracellular signal-regulated kinase expression in the lungs.
      In conclusion, CO exerts potent protective effects on lungs from BD rats,
      exhibiting anti-inflammatory and anti-apoptosis functions by modulating the
      mitogen-activated protein kinase signal transduction.

PMID- 20810761
TI  - Establishment of self-sequential longitudinal reference intervals of maternal
      thyroid function during pregnancy.
AB  - The objective of this study is to establish self-sequential longitudinal
      reference intervals of thyroid function in normal pregnant women. According to
      the selection criteria, 301 cases were taken as the normal pregnant population to
      establish a normal reference range. Meanwhile, 150 healthy women were selected as
      the normal non-pregnant control group. To establish their own self-sequential
      longitudinal reference intervals, we collected samples five times in every case
      throughout the gestation (including first trimester, second trimester, third
      trimester, prenatal and postpartum), and detected the levels of thyroid
      stimulating hormone (TSH), free thyroxine (FT4), thyroid peroxidase antibodies
      (TPO-Ab), and then established the self-sequential longitudinal reference
      intervals. The levels of TSH, FT4 and TPO-Ab were quantified by electrochemistry
      immunoassay (ECL) and statistically analyzed using SPSS 13.0 software. Serum TSH
      of normal pregnant women was at a low level in the first trimester (P < 0.05) and
      began to rise continuously. Not until prenatal phase was it restored to the non
      pregnant state (P > 0.05). During pregnancy, serum FT4 of normal pregnant women
      were consistently lower than non-pregnant levels (P < 0.05) and kept at low
      levels. Serum TPO-Ab increased significantly in the third trimester and prenatal
      phase (P < 0.05). Of normal pregnant women, 6.5% were TPO-Ab positive. In
      conclusion, the reference intervals in our case will reflect the changes of
      thyroid function in pregnant women more realistically, resulting in a more
      accurate value for clinical diagnosis and therapy.

PMID- 20810762
TI  - Chronic shedders as reservoir for nosocomial transmission of norovirus.
AB  - Norovirus (NoV) infection in immunocompromised patients may lead to prolonged
      norovirus shedding. Here, we demonstrate the involvement of three chronic
      shedders in hospital outbreaks. Combined epidemiological and molecular evidence
      suggests that in one case, NoV transmission occurred at least 17 days after the
      first diagnosis.

PMID- 20810763
TI  - Spoligotype-based comparative population structure analysis of multidrug
      resistant and isoniazid-monoresistant Mycobacterium tuberculosis complex clinical
      isolates in Poland.
AB  - The spoligotyping-based population structure of multidrug-resistant (MDR)
      Mycobacterium tuberculosis strains isolated in Poland (n = 46), representing all
      culture-positive MDR tuberculosis (MDR-TB) cases, was compared to that of
      isoniazid (INH)-monoresistant strains (n = 71) isolated in 2004. The latter data
      set from a previous study (E. Augustynowicz-Kopec, T. Jagielski, and Z. Zwolska,
      J. Clin. Microbiol. 2008, 46:4041-4044) represented 87% of all INH-monoresistant
      strains. The clustering rates and genotypic-diversity indexes for the 2
      subpopulations were not significantly different (P = 0.05). The results were
      entered in the SITVIT2 database to assign specific shared type designations,
      corresponding genotypic lineages, and geographical distributions and compared to
      available data from neighboring countries (Germany, n = 704; Czech Republic, n =
      530; Sweden, n = 379; Kaliningrad, Russia, n = 90) and strains from previous
      studies in Poland (n = 317). MDR strains resulted in 27 patterns (20 unique
      strains within the study and 7 clusters containing 2 to 6 isolates per cluster
      with a clustering rate of 56.5%) and belonged to the following genotypic
      lineages: ill-defined T family (28.3%), Haarlem (17.4%), Latin American and
      Mediterranean (LAM) (13%), Beijing (8.7%), S family (4.35%), and the X clade
      (2.17%). Comparison of the genetic structure of the MDR strains with that of INH
      monoresistant strains showed that a total of 9 patterns were shared by both
      groups; these represented 1/3 of the MDR strains and 2/3 of the INH-monoresistant
      strains. Interestingly, 76.1% of the MDR isolates and 71.8% of the INH-resistant
      isolates yielded spoligotypes that were previously reported from Poland. The
      observation that nearly half of the spoligotypes identified among both MDR
      (48.1%) and INH-monoresistant (43.3%) M. tuberculosis isolates were present in
      Poland's neighboring countries suggested that a significant proportion of MDR and
      INH-resistant TB cases in Poland were caused by strains actively circulating in
      Poland or its neighbors. Our results corroborate the leading role of the T and
      Haarlem genotypes in the epidemiology of drug-resistant TB in Poland.
      Nevertheless, the LAM and Beijing family strains that infected, correspondingly,
      13% and 9% of patients with MDR-TB were absent among the strains from patients
      with INH-monoresistant TB, suggesting that a proportion of MDR-TB cases in Poland
      are due to ongoing transmission of MDR clones exhibiting specific genotypes.
      Study of the population genetic relationships between MDR and INH-monoresistant
      strains by drawing minimum spanning trees showed that ill-defined T1 sublineage
      strains (1/3 of all INH-monoresistant strains), represented by its prototype,
      SIT53, constituted the central node of the tree, followed by strains belonging to
      the well-defined H3, H1, and S subgroups. However, the MDR group, in addition,
      contained LAM (n = 6) and Beijing (n = 4) lineage isolates. With the exception of
      the 4 Beijing lineage strains in the latter group and a single orphan isolate in
      the INH-monoresistant group, none of the remaining 112/117 isolates belonged to
      principal genetic group 1 (PGG1) in our study. Given the high rate of clustering
      and the near absence of immigrants in the study, the persistence of MDR-TB in
      Poland seems to result from active transmission of MDR strains within the
      autochthonous population, the bulk of it caused by evolutionarily recent tubercle
      bacilli.

PMID- 20810764
TI  - Robust hepatitis B virus genotyping by mass spectrometry.
AB  - Genotyping of hepatitis B virus (HBV) is important for tracking HBV infections,
      prognosticating the development of severe liver disease, and predicting outcomes
      of therapy. Current genotyping methods can be laborious and costly and rely on
      subjective data interpretation. To identify less expensive but equally reliable
      alternatives, we compared "gold standard" sequencing to a novel mass spectrometry
      approach. Sera from individuals with acute or chronic HBV infection (n = 756),
      representing all genotypes, were used to PCR amplify the HBV S gene. All
      amplicons were subjected to base-specific cleavage and matrix-assisted laser
      desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). The
      resulting mass peak patterns were used to identify HBV genotype by automated
      comparison to peak patterns simulated from reference sets of HBV sequences of
      known genotypes. The MALDI-TOF MS data and phylogenetic analysis of HBV sequences
      produced completely concordant results. Several parameters such as genetic
      relatedness of tested HBV variants to the reference set, chronic infections, and
      the quality of PCR products can lower the MS score but never affected the
      accuracy of the genotype call. This new streamlined MS-based method provides for
      rapid and accurate HBV genotyping, produces automated data reports, and is
      therefore suitable for routine use in diagnostic settings.

PMID- 20810765
TI  - Comparison of premier CAMPY enzyme immunoassay (EIA), ProSpecT Campylobacter EIA,
      and ImmunoCard STAT! CAMPY tests with culture for laboratory diagnosis of
      Campylobacter enteric infections.
AB  - Campylobacter enteritis is a food-borne or waterborne illness caused almost
      exclusively by Campylobacter jejuni and, to a lesser extent, by Campylobacter
      coli. These organisms produce indistinguishable clinical diseases and together
      represent the second most common cause of bacterial diarrhea in the United States
      and the leading cause of enteric infection throughout the world. The conventional
      approach to the laboratory diagnosis of Campylobacter enteritis is based on the
      recovery of the organism from a stool specimen, which requires the use of a
      specialized medium incubated at 42 degrees C for several days in an artificially
      created microaerophilic environment. Recently, several commercially available
      enzyme immunoassays (EIAs) have been developed for the direct detection of C.
      jejuni and C. coli in stool specimens. This study compared conventional culture
      with three EIA methods, the Premier CAMPY EIA (Meridian Bioscience, Cincinnati,
      OH), the ProSpecT Campylobacter EIA (Remel, Lenexa, KS), and the ImmunoCard STAT!
      CAMPY test (Meridian Bioscience, Cincinnati, OH), for the detection of C. jejuni
      and C. coli in 485 patient stool samples. Discordant results were arbitrated by
      using an in-house, real-time PCR assay that was developed and validated by a
      public health reference laboratory. Following analyses of the discrepant
      specimens by PCR, the sensitivity and specificity of both the Premier CAMPY and
      ProSpecT Campylobacter EIAs were 99.3% and 98%, respectively, while the
      ImmunoCard STAT! CAMPY test had a sensitivity of 98.5% and a specificity of
      98.2%. By use of the PCR test as the reference standard, culture detected 127 of
      135 Campylobacter-positive stool specimens, yielding a sensitivity of 94.1%.
      These results showed that the three EIAs evaluated in this study provide a rapid
      and reliable alternative for the laboratory diagnosis of enteric infections with
      C. jejuni and C. coli and that conventional culture may no longer be recognized
      as the "gold standard" for diagnosis.

PMID- 20810766
TI  - Identification of potential diagnostic markers among Burkholderia cenocepacia and
      B. multivorans supernatants.
AB  - Patients with cystic fibrosis (CF) are susceptible to chronic respiratory
      infections with a number of bacterial pathogens. Among them, the Burkholderia
      cepacia complex (Bcc) bacteria, consisting of nine related species, have emerged
      as problematic CF pathogens due to their antibiotic resistance, incidence of
      nosocomial infection, and person-to-person transmission. Bcc organisms present
      the clinical microbiologist with a diagnostic dilemma due to the lack of
      phenotypic biochemical or growth-related characterization tests that reliably
      distinguish among these organisms. The complex taxonomy of the Bcc species
      colonizing the CF respiratory tract makes accurate identification problematic.
      Despite the clinical implications of Bcc identification, a clinical laboratory
      differentiation of species within the Bcc is lacking. Additionally, no commercial
      assays are available to further identify the Bcc species. In the current study,
      secretory proteins present in the cultured supernatants of Burkholderia
      cenocepacia and Burkholderia multivorans were analyzed by two-dimensional gel
      electrophoresis (2-DE), followed by matrix-assisted laser desorption ionization
      time of flight mass spectrometry (MALDI-TOF MS). To assess differential
      expression, protein spots of B. cenocepacia and B. multivorans that were unique
      or displayed different intensities were chosen for MALDI-TOF MS analysis. In
      total, 341 protein spots were detected, of which 23 were unique to each species,
      demonstrating that potential diagnostic candidates between these two members of
      the Bcc exist.

PMID- 20810767
TI  - Cholera toxin production by the El Tor variant of Vibrio cholerae O1 compared to
      prototype El Tor and classical biotypes.
AB  - Vibrio cholerae O1 El Tor variant strains produced much more cholera toxin than
      did prototype El Tor strains. The amount of cholera toxin produced by El Tor
      variant strains both in vitro and in vivo was more or less equivalent to that
      produced by classical strains.

PMID- 20810768
TI  - secA1 gene sequence polymorphisms for species identification of Nocardia species
      and recognition of intraspecies genetic diversity.
AB  - Sequence analysis of the Nocardia essential secretory protein SecA1 gene (secA1)
      for species identification of 120 American Type Culture Collection (ATCC) and
      clinical isolates of Nocardia (16 species) was studied in comparison with 5'-end
      606-bp 16S rRNA gene sequencing. Species determination by both methods was
      concordant for all 10 ATCC strains. secA1 gene sequencing provided the same
      species identification as 16S rRNA gene analysis for 94/110 (85.5%) clinical
      isolates. However, 40 (42.6%) isolates had sequences with <99.0% similarity to
      archived secA1 sequences for the species, including 29 Nocardia cyriacigeorgica
      (96.6 to 98.9% similarity) and 4 Nocardia veterana (91.5 to 98.9% similarity)
      strains. Discrepant species identification was obtained for 16 (14.5%) clinical
      isolates, including 13/23 Nocardia nova strains (identified as various Nocardia
      species by secA1 sequencing) and 1 isolate each of Nocardia abscessus (identified
      as Nocardia asiatica), Nocardia elegans (Nocardia africana), and Nocardia
      transvalensis (Nocardia blacklockiae); both secA1 gene sequence analysis and
      deduced amino acid sequence analysis determined the species to be different from
      those assigned by 16S rRNA gene sequencing. The secA1 locus showed high sequence
      diversity (66 sequence or genetic types versus 40 16S rRNA gene sequence types),
      which was highest for N. nova (14 secA1 sequence types), followed by Nocardia
      farcinica and N. veterana (n = 7 each); there was only a single sequence type
      among eight Nocardia paucivorans strains. The secA1 locus has potential for
      species identification as an adjunct to 16S rRNA gene sequencing but requires
      additional deduced amino acid sequence analysis. It may be a suitable marker for
      phylogenetic/subtyping studies.

PMID- 20810769
TI  - Molecular epidemiology of Streptococcus pneumoniae serogroup 6 isolates from
      Fijian children, including newly identified serotypes 6C and 6D.
AB  - Multilocus sequence typing (MLST) was applied to all unique serotype 6C and 6D
      isolates and a random selection of serotype 6B and 6A isolates from
      nasopharyngeal swabs from Fijian children enrolled in a recent vaccine trial. The
      results suggest that Fijian serotype 6D has arisen independently from both
      serotypes 6A/C and 6B.

PMID- 20810770
TI  - Impact of long-term storage on stability of standard DNA for nucleic acid-based
      methods.
AB  - Real-time PCR is dependent upon a calibration function for quantification. While
      long-term storage of standards saves cost and time, solutions of DNA are prone to
      degradation. We present here the benchmark treatment for preservation of DNA
      standards, involving storage in 50% glycerol-double-distilled water, whereby a
      deviation of 0.2 threshold cycle (C(T)) values resulted after 100 days of
      storage.

PMID- 20810771
TI  - Human cytomegalovirus UL144 is associated with viremia and infant development
      sequelae in congenital infection.
AB  - Human cytomegalovirus (HCMV) strains may be genotyped based on polymorphisms that
      exist within the UL144 gene, which is one of 19 viral genes lost in attenuated
      laboratory strains. In the present study, UL144 genotypes in congenitally
      infected babies (congenital cytomegalovirus [cCMV]) were determined, and the
      relationship between the genotype, viral load, cytokine profile, and patient
      developmental outcome was investigated. All cCMV infections identified during
      2006 and 2007 were included (n = 29). A portion of the infants were clinically
      assessed at birth and at 12 to 18 months postinfection for cCMV clinical sequelae
      (n = 18/29). The plasma viral load (PVL) was requested for 23/29 patients, and
      the UL144 genotype was determined (n = 27/29). The cytokine profile in patient
      plasma or serum was assessed (n = 20/29). UL144 genotypes A, B, and C were
      detected within the cCMV population at 33.3%, 29.6%, and 25.9%, respectively.
      UL144 A and C were associated with a high PVL (P < 0.04). Furthermore, a
      significant association between the developmental outcome and UL144 A and C was
      observed (P < 0.04). Only patients infected with UL144 B and A/B were described
      as having a normal clinical outcome. In addition, a significant correlation
      between interleukin 10 (IL-10) levels and the PVL was observed (P < 0.04);
      however, there was no association between the genotype and the cytokine profile.
      The present study determined that the specific detection of UL144 genotypes A and
      C was indicative of serious cCMV infection and more likely to lead to long-term
      cCMV-associated clinical manifestations. The inclusion of HCMV UL144 genotyping
      along with the recommended PVL monitoring following cCMV diagnosis may aid
      prediction of the clinical outcome.

PMID- 20810772
TI  - Improved PCR methods for detection of African rabies and rabies-related
      lyssaviruses.
AB  - Eleven different lyssavirus species, four of which occur on the African
      continent, are presently recognized. These viruses cause rabies, the burden of
      which is highest in the developing world, where routine laboratory diagnosis is
      often not available. From an epidemiological and control perspective, it is
      necessary that diagnostic methods detect the diversity of lyssaviruses present in
      different regions of the world. A published and widely used heminested reverse
      transcription-PCR (hnRT-PCR) was evaluated for its ability to detect a panel of
      diverse African lyssaviruses. Due to the limitations experienced for this assay,
      an alternative hnRT-PCR was developed. The new assay was found to be accurate and
      sensitive in the detection of African lyssavirus RNA in a variety of clinical
      specimens. The assay was further adapted to a real-time PCR platform to allow
      rapid, one-step, quantitative, and single-probe detection, and an internal
      control for the verification of sample preparation was included. The limit of
      detection of the real-time PCR assay was 10 RNA copies per reaction, with inter-
      and intra-assay variability below 4%. Subsequently, in demonstrating utility,
      both assays were successfully applied to antemortem rabies diagnosis in humans.
      We believe that the quantitative real-time PCR assay could find application as a
      routine confirmatory test for rabies diagnosis in the future and that it will
      serve as a valuable research tool in the biology of African lyssaviruses.
      Alternatively, the hnRT-PCR assay can be used in laboratories that do not have
      access to expensive real-time PCR equipment for sensitive diagnosis of
      lyssaviruses.

PMID- 20810773
TI  - Variability of the polymerase gene (NS5B) in hepatitis C virus-infected women.
AB  - There are limited data on diversity within the hepatitis C virus polymerase
      (NS5B). In concordance with its key functional role during the life cycle, NS5B
      intrapatient variability was low. Moreover, differences between NS5B
      nonsynonymous (dN) and synonymous (dS) mutation rates (dN - dS) were positively
      correlated with CD4 cell count, while nonsynonymous mutations were strongly
      correlated with reduced replication in vivo.

PMID- 20810774
TI  - Outbreak of neonatal gastroenteritis associated with astrovirus serotype 1 at a
      hospital in Inner Mongolia, China.
AB  - This report describes for the first time an outbreak of acute gastroenteritis
      among neonates associated with human astrovirus (HAstV) serotype 1b at a
      maternity hospital in Inner Mongolia, China. Of 40 specimens, 28 were astrovirus
      positive and rotavirus, calicivirus, and adenovirus negative. Poor hygiene likely
      contributed to the spread and persistence of HAstV in the neonatal care room.

PMID- 20810775
TI  - Evaluation of mupA EVIGENE assay for determination of high-level mupirocin
      resistance in Staphylococcus aureus.
AB  - Mupirocin is widely used to decolonize patients carrying Staphylococcus aureus,
      especially methicillin-resistant S. aureus (MRSA). The aim of this study was to
      determine the presence of high-level mupirocin resistance by a new commercially
      available mupA genotypic diagnostic product, mupA EVIGENE assay (AdvanDx).

PMID- 20810776
TI  - Human respiratory syncytial virus in children with acute respiratory tract
      infections in China.
AB  - There are limited data on the prevalence and clinical and molecular
      characterization of human respiratory syncytial virus (HRSV) in children with
      acute respiratory tract infections (ARTIs) in China. From December 2006 to March
      2009, 894 nasopharyngeal aspirates (NPAs) were collected from children under 14
      years of age with ARTIs. Samples were screened for HRSV and genotyped by reverse
      transcription-PCR (RT-PCR) and sequencing. Demographic and clinical information
      was recorded. A total of 38.14% (341/894) of samples were positive for HRSV.
      Phylogenetic analysis revealed that 60.4% of the selected 227 RSV strains were
      GA2, 34.4% were BA, 4.8% were GB2, and 0.4% were GB3. A total of 40.47% of all of
      the RSV-positive samples were coinfected with other respiratory viruses, and
      adenovirus was the most common additional respiratory virus. No statistical
      differences were found in the frequency of diagnosis and symptoms between the
      coinfection group and monoinfection group. Additionally, no statistical
      differences were found in epidemiological characterizations or disease severity
      between genotype BA- and GA2-positive patients, except for a greater frequency of
      lower respiratory tract infections (LRTIs) (mostly bronchitis)with BA. HRSV is
      the most important viral pathogen in Chinese children with ARTIs. Four genotypes
      (i.e., GA2, BA, GB2, and GB3) circulate locally, and the predominant genotype may
      shift between seasons. Coinfection with other viruses does not affect disease
      severity. HRSV genotypes were not associated with different epidemiological
      characterizations or disease severity.

PMID- 20810778
TI  - Detection of human cytomegalovirus in bronchoalveolar lavage fluid of lung
      transplant recipients reflects local virus replication and not contamination from
      the throat.
AB  - Whether bronchoalveolar lavage (BAL) fluid may be contaminated with oropharyngeal
      cytomegalovirus (CMV) has never been investigated. In an analysis of CMV DNA
      loads in 76 simultaneously obtained BAL fluid and throat wash samples from lung
      transplant recipients, we show that such contamination is unlikely and that
      detection of CMV DNA in BAL fluid reflects virus replication in the lung.

PMID- 20810777
TI  - Rapid detection of multidrug-resistant Mycobacterium tuberculosis by use of real
      time PCR and high-resolution melt analysis.
AB  - The current study describes the development of a unique real-time PCR assay for
      the detection of mutations conferring drug resistance in Mycobacterium
      tuberculosis. The rifampicin resistance determinant region (RRDR) of rpoB and
      specific regions of katG and the inhA promoter were targeted for the detection of
      rifampin (RIF) and isoniazid (INH) resistance, respectively. Additionally, this
      assay was multiplexed to discriminate Mycobacterium tuberculosis complex (MTC)
      strains from nontuberculous Mycobacteria (NTM) strains by targeting the IS6110
      insertion element. High-resolution melting (HRM) analysis following real-time PCR
      was used to identify M. tuberculosis strains containing mutations at the targeted
      loci, and locked nucleic acid (LNA) probes were used to enhance the detection of
      strains containing specific single-nucleotide polymorphism (SNP) transversion
      mutations. This method was used to screen 252 M. tuberculosis clinical isolates,
      including 154 RIF-resistant strains and 174 INH-resistant strains based on the
      agar proportion method of drug susceptibility testing (DST). Of the 154 RIF
      resistant strains, 148 were also resistant to INH and therefore classified as
      multidrug resistant (MDR). The assay demonstrated sensitivity and specificity of
      91% and 98%, respectively, for the detection of RIF resistance and 87% and 100%
      for the detection of INH resistance. Overall, this assay showed a sensitivity of
      85% and a specificity of 98% for the detection of MDR strains. This method
      provides a rapid, robust, and inexpensive way to detect the dominant mutations
      known to confer MDR in M. tuberculosis strains and offers several advantages over
      current molecular and culture-based techniques.

PMID- 20810779
TI  - Efficient differentiation of Mycobacterium avium complex species and subspecies
      by use of five-target multiplex PCR.
AB  - Infections caused by the Mycobacterium avium complex (MAC) are on the rise in
      both human and veterinary medicine. A means of effectively discriminating among
      closely related yet pathogenetically diverse members of the MAC would enable
      better diagnosis and treatment as well as further our understanding of the
      epidemiology of these pathogens. In this study, a five-target multiplex PCR
      designed to discriminate MAC organisms isolated from liquid culture media was
      developed. This MAC multiplex was designed to amplify a 16S rRNA gene target
      common to all Mycobacterium species, a chromosomal target called DT1 that is
      unique to M. avium subsp. avium serotypes 2 and 3, to M. avium subsp. silvaticum,
      and to M. intracellulare, and three insertion sequences, IS900, IS901, and
      IS1311. The pattern of amplification results allowed determination of whether
      isolates were mycobacteria, whether they were members of the MAC, and whether
      they belonged to one of three major MAC subspecies, M. avium subsp.
      paratuberculosis, M. avium subsp. avium, and M. avium subsp. hominissuis.
      Analytical sensitivity was 10 fg of M. avium subsp. paratuberculosis genomic DNA,
      5 to 10 fg of M. avium subsp. avium genomic DNA, and 2 to 5 fg of DNA from other
      mycobacterial species. Identification accuracy of the MAC multiplex was evaluated
      by testing 53 bacterial reference strains consisting of 28 different
      mycobacterial species and 12 nonmycobacterial species. Identification accuracy in
      a clinical setting was evaluated for 223 clinical MAC isolates independently
      identified by other methods. Isolate identification agreement between the MAC
      multiplex and these comparison assays was 100%. The novel MAC multiplex is a
      rapid, reliable, and simple assay for discrimination of MAC species and
      subspecies in liquid culture media.

PMID- 20810780
TI  - Dabigatran inhibits Staphylococcus aureus coagulase activity.
AB  - The ability of Staphylococcus aureus to clot plasma through conformational
      activation of prothrombin by staphylocoagulase is used to distinguish S. aureus
      from coagulase-negative staphylococci. We show that while the direct thrombin
      inhibitor dabigatran inhibits staphylocoagulase activity, the clinical use of
      dabigatran etexilate is not expected to interfere with direct tube coagulase
      testing.

PMID- 20810781
TI  - It's not easy being green: the viridans group streptococci, with a focus on
      pediatric clinical manifestations.
AB  - The viridans group streptococci (VGS) are a heterogeneous group of organisms that
      can be human commensals, colonizing the gastrointestinal and genitourinary tracts
      in addition to the oral mucosa. VGS are generally considered to be of low
      pathogenic potential in immunocompetent individuals. However, in certain patient
      populations, VGS can cause invasive disease, such as endocarditis, intra
      abdominal infection, and shock. Within the VGS, the rates and patterns of
      antimicrobial resistance vary greatly depending upon the species identification
      and the patient population. In general, Streptococcus mitis group organisms are
      resistant to more antimicrobial agents than the other VGS species. This review
      addresses current VGS taxonomy, in addition to the current methodologies being
      used in clinical microbiology laboratories for identification of VGS. Automated
      systems struggle overall with species level identification and susceptibility
      testing for VGS. Matrix-assisted laser desorption ionization-time of flight
      (MALDI-TOF) identification is emerging as a potential alternative for organism
      identification. A review of recent pediatric-specific data regarding the clinical
      manifestations of VGS revealed that the Streptococcus anginosus group (SAG)
      organisms may be important pathogens in pediatric patients and that the VGS may
      contribute to disease in patients with cystic fibrosis. It also appears that
      rates of antimicrobial resistance in VGS in pediatric patients are surpassing
      those of the adult population.

PMID- 20810782
TI  - Superior pole sleeve fracture of the patella: a case report and review of the
      literature.

PMID- 20810783
TI  - Chemotaxis: insights from the extending pseudopod.
AB  - Chemotaxis is one of the most fascinating processes in cell biology. Shallow
      gradients of chemoattractant direct the movement of cells, and an intricate
      network of signalling pathways somehow instructs the movement apparatus to induce
      pseudopods in the direction of these gradients. Exciting new experiments have
      approached chemotaxis from the perspective of the extending pseudopod. These
      recent studies have revealed that, in the absence of external cues, cells use
      endogenous signals for the highly ordered extension of pseudopods, which appear
      mainly as alternating right and left splits. In addition, chemoattractants
      activate other signalling molecules that induce a positional bias of this basal
      system, such that the extending pseudopods are oriented towards the gradient. In
      this Commentary, I review the findings of these recent experiments, which
      together provide a new view of cell movement and chemotaxis.

PMID- 20810785
TI  - Effects of selenite and chelating agents on mammalian thioredoxin reductase
      inhibited by mercury: implications for treatment of mercury poisoning.
AB  - Mercury toxicity is a highly interesting topic in biomedicine due to the severe
      endpoints and treatment limitations. Selenite serves as an antagonist of mercury
      toxicity, but the molecular mechanism of detoxification is not clear. Inhibition
      of the selenoenzyme thioredoxin reductase (TrxR) is a suggested mechanism of
      toxicity. Here, we demonstrated enhanced inhibition of activity by inorganic and
      organic mercury compounds in NADPH-reduced TrxR, consistent with binding of
      mercury also to the active site selenolthiol. On treatment with 5 MUM selenite
      and NADPH, TrxR inactivated by HgCl(2) displayed almost full recovery of
      activity. Structural analysis indicated that mercury was complexed with TrxR, but
      enzyme-generated selenide removed mercury as mercury selenide, regenerating the
      active site selenocysteine and cysteine residues required for activity. The
      antagonistic effects on TrxR inhibition were extended to endogenous antioxidants,
      such as GSH, and clinically used exogenous chelating agents BAL, DMPS, DMSA, and
      alpha-lipoic acid. Consistent with the in vitro results, recovery of TrxR
      activity and cell viability by selenite was observed in HgCl(2)-treated HEK 293
      cells. These results stress the role of TrxR as a target of mercurials and
      provide the mechanism of selenite as a detoxification agent for mercury
      poisoning.

PMID- 20810784
TI  - Functional interactions as a survival strategy against abnormal aggregation.
AB  - Protein aggregation is under intense scrutiny because of its role in human
      disease. Although increasing evidence indicates that protein native states are
      highly protected against aggregation, the specific protection mechanisms are
      poorly understood. Insight into such mechanisms can be gained through study of
      the relatively few proteins that aggregate under native conditions. Ataxin-3, the
      protein responsible for Spinocerebellar ataxia type 3, a polyglutamine expansion
      disease, represents one of such examples. Polyglutamine expansion is central for
      determining solubility and aggregation rates of ataxin-3, but these properties
      are profoundly modulated by its N-terminal Josephin domain. This work aims at
      identifying the regions that promote Josephin fibrillogenesis and rationalizing
      the mechanisms that protect Josephin and nonexpanded ataxin-3 from aberrant
      aggregation. Using different biophysical techniques, aggregation propensity
      predictions and rational design of amino acid substitutions, we show that
      Josephin has an intrinsic tendency to fibrillize under native conditions and that
      fibrillization is promoted by two solvent-exposed patches, which are also
      involved in recognition of natural substrates, such as ubiquitin. Indeed,
      designed mutations at these patches or substrate binding significantly reduce
      Josephin aggregation kinetics. Our results provide evidence that protein
      nonpathologic function can play an active role in preventing aberrant
      fibrillization and suggest the molecular mechanism whereby this occurs in ataxin
      3.

PMID- 20810786
TI  - Adducins regulate remodeling of apical junctions in human epithelial cells.
AB  - Epithelial adherens junctions (AJs) and tight junctions (TJs) are dynamic
      structures that readily undergo disintegration and reassembly. Remodeling of the
      AJs and TJs depends on the orchestrated dynamics of the plasma membrane with its
      underlying F-actin cytoskeleton, and the membrane-cytoskeleton interface may play
      a key role in junctional regulation. Spectrin-adducin-ankyrin complexes link
      membranes to the actin cytoskeleton where adducins mediate specrtrin-actin
      interactions. This study elucidates roles of adducins in the remodeling of
      epithelial junctions in human SK-CO15 colonic and HPAF-II pancreatic epithelial
      cell monolayers. These cells expressed the alpha and gamma isoforms of adducin
      that positively regulated each others protein level and colocalized with E
      cadherin and beta-catenin at mature, internalized and newly assembled AJs. Small
      interfering RNA-mediated down-regulation of alpha- or gamma-adducin expression
      significantly attenuated calcium-dependent AJ and TJ assembly and accelerated
      junctional disassembly triggered by activation of protein kinase C. Two
      mechanisms were found to mediate the impaired AJ and TJ assembly in adducin
      depleted cells. One mechanism involved diminished expression and junctional
      recruitment of betaII-spectrin, and the other mechanism involved the decrease in
      the amount of cellular F-actin and impaired assembly of perijunctional actin
      bundles. These findings suggest novel roles for adducins in stabilization of
      epithelial junctions and regulation of junctional remodeling.

PMID- 20810787
TI  - Involvement of p114-RhoGEF and Lfc in Wnt-3a- and dishevelled-induced RhoA
      activation and neurite retraction in N1E-115 mouse neuroblastoma cells.
AB  - The Wnt-induced planar cell polarity (PCP) signaling pathway is essential for
      polarized cell migration and morphogenesis. Dishevelled (Dvl) and its binding
      protein Daam1 mediate RhoA activation in this pathway. WGEF, a member of the Rho
      guanine nucleotide exchange factor (Rho-GEF) family, was shown to play a role in
      Wnt-induced RhoA activation in Xenopus embryos. However, it has remained unknown
      which member(s) of a Rho-GEF family are involved in Wnt/Dvl-induced RhoA
      activation in mammalian cells. Here we identified p114-RhoGEF and Lfc (also
      called GEF-H1) as the Rho-GEFs responsible for Wnt-3a-induced RhoA activation in
      N1E-115 mouse neuroblastoma cells. We screened for Rho-GEF-silencing short
      hairpin RNAs (shRNAs) that are capable of suppressing Dvl-induced neurite
      retraction in N1E-115 cells and found that p114-RhoGEF and Lfc shRNAs, but not
      WGEF shRNA, suppressed Dvl- and Wnt-3a-induced neurite retraction. p114-RhoGEF
      and Lfc shRNAs also inhibited Dvl- and Wnt-3a-induced RhoA activation, and p114
      RhoGEF and Lfc proteins were capable of binding to Dvl and Daam1. Additionally,
      the Dvl-binding domains of p114-RhoGEF and Lfc inhibited Dvl-induced neurite
      retraction. Our results suggest that p114-RhoGEF and Lfc are critically involved
      in Wnt-3a- and Dvl-induced RhoA activation and neurite retraction in N1E-115
      cells.

PMID- 20810789
TI  - 21-year-old woman with palpitations and vomiting.

PMID- 20810788
TI  - Phosphorylation of p27Kip1 at Thr187 by cyclin-dependent kinase 5 modulates
      neural stem cell differentiation.
AB  - Cyclin-dependent kinase 5 (Cdk5) plays a key role in the development of the
      mammalian nervous system; it phosphorylates a number of targeted proteins
      involved in neuronal migration during development to synaptic activity in the
      mature nervous system. Its role in the initial stages of neuronal commitment and
      differentiation of neural stem cells (NSCs), however, is poorly understood. In
      this study, we show that Cdk5 phosphorylation of p27(Kip1) at Thr187 is crucial
      to neural differentiation because 1) neurogenesis is specifically suppressed by
      transfection of p27(Kip1) siRNA into Cdk5(+/+) NSCs; 2) reduced neuronal
      differentiation in Cdk5(-/-) compared with Cdk5(+/+) NSCs; 3) Cdk5(+/+) NSCs,
      whose differentiation is inhibited by a nonphosphorylatable mutant, p27/Thr187A,
      are rescued by cotransfection of a phosphorylation-mimicking mutant, p27/Thr187D;
      and 4) transfection of mutant p27(Kip1) (p27/187A) into Cdk5(+/+) NSCs inhibits
      differentiation. These data suggest that Cdk5 regulates the neural
      differentiation of NSCs by phosphorylation of p27(Kip1) at theThr187 site.
      Additional experiments exploring the role of Ser10 phosphorylation by Cdk5
      suggest that together with Thr187 phosphorylation, Ser10 phosphorylation by Cdk5
      promotes neurite outgrowth as neurons differentiate. Cdk5 phosphorylation of
      p27(Kip1), a modular molecule, may regulate the progress of neuronal
      differentiation from cell cycle arrest through differentiation, neurite
      outgrowth, and migration.

PMID- 20810790
TI  - Medical images. Bone tenderness.

PMID- 20810791
TI  - Aggressive approach to pulmonary embolectomy for massive acute pulmonary
      embolism: a historical and contemporary perspective.

PMID- 20810792
TI  - A more aggressive approach to emergency embolectomy for acute pulmonary embolism.
AB  - OBJECTIVE: To examine operative outcomes after acute pulmonary embolectomy (APE),
      a recently adopted, more aggressive surgical approach. PATIENTS AND METHODS: We
      retrospectively identified patients who underwent surgical APE from April 1,
      2001, through March 31, 2009, and reviewed their clinical records for
      perioperative outcome. Operations were performed with normothermic
      cardiopulmonary bypass and a beating heart, absent a patent foramen ovale. For
      completeness, embolectomy was performed via separate incisions in the left and
      right pulmonary arteries (PAs) in 15 patients. RESULTS: Of the 18 patients
      identified, the mean age was 60 years, and 13 patients (72%) were men. Thirteen
      patients (72%) had been hospitalized recently or had systemic disease. The
      preoperative diagnosis was established by echocardiography or computed tomography
      (or both). The median (range) follow-up time for all surviving patients was 16
      months (2-74 months). Indications for APE included cardiogenic shock (n=12; 67%)
      and severe right ventricular dysfunction as shown by echocardiography (n=5; 28%).
      Seven patients (39%) had an embolus in transit. Seven patients (39%) experienced
      cardiopulmonary arrest before APE. Four early deaths (22%) occurred; all 4 of
      these patients had preoperative cardiopulmonary arrest, and 2 had APE via the
      main PA only, without branch PA incisions. Two late deaths (11%) occurred. Right
      ventricular function improved in all survivors. CONCLUSION: The results of
      emergent APE are encouraging, particularly among patients without cardiopulmonary
      arrest. It should not be reserved for patients in extremis; rather, it should be
      considered for patients with right ventricular dysfunction that is an early sign
      of impending hemodynamic collapse.

PMID- 20810795
TI  - Clinical pearls in dermatology.

PMID- 20810793
TI  - Endothelial nitric oxide synthase gene variation associated with chronic kidney
      disease after liver transplant.
AB  - OBJECTIVE: To identify single nucleotide polymorphisms (SNPs) associated with
      risk of developing chronic kidney disease (CKD), a prevalent comorbidity, after
      liver transplant (LT). PATIENTS AND METHODS: This study consists of a cohort of
      adult (> or =18 years) primary-LT recipients who had normal renal function before
      LT and who survived 1 year or more after LT at a high-volume US LT program
      between January 1, 1990, and December 31, 2000. Patients with adequate renal
      function (estimated glomerular filtration rate, > or =40 mL/min per 1.73 m(2)
      during follow-up; n=308) and patients with incident CKD (estimated glomerular
      filtration rate, <40 mL/min per 1.73 m(2) after LT; n=92) were identified. To
      investigate the association of 6 candidate genes with post-LT CKD, we selected
      SNPs that have been associated with renal function in the literature. Hazard
      ratios were estimated using Cox regression, adjusted for potential confounding
      variables. RESULTS: The variant allele (298Asp) of the Glu298Asp SNP in the
      endothelial nitric oxide synthase gene (NOS3) was significantly associated with
      CKD after LT (P=.05; adjusted for multiple comparisons). The 5-year incidence of
      CKD was 70% among patients homozygous for the NOS3 variant allele (298Asp)
      compared with 42% among those not homozygous for the NOS3 variant allele.
      Specifically, homozygosity for the NOS3 variant allele conferred a 2.5-fold
      increased risk of developing CKD after LT (P=.005, adjusted for confounding
      variables). CONCLUSION: Homozygosity for the variant allele of NOS3 (298Asp) is
      associated with CKD after LT and may be useful for identifying recipients at
      higher risk of post-LT CKD.

PMID- 20810796
TI  - 82-year-old man with bilateral leg swelling.

PMID- 20810797
TI  - Cardiac thrombi in stress (tako-tsubo) cardiomyopathy: more than an apical issue?

PMID- 20810794
TI  - Paraneoplastic syndromes: an approach to diagnosis and treatment.
AB  - Recent medical advances have improved the understanding, diagnosis, and treatment
      of paraneoplastic syndromes. These disorders arise from tumor secretion of
      hormones, peptides, or cytokines or from immune cross-reactivity between
      malignant and normal tissues. Paraneoplastic syndromes may affect diverse organ
      systems, most notably the endocrine, neurologic, dermatologic, rheumatologic, and
      hematologic systems. The most commonly associated malignancies include small cell
      lung cancer, breast cancer, gynecologic tumors, and hematologic malignancies. In
      some instances, the timely diagnosis of these conditions may lead to detection of
      an otherwise clinically occult tumor at an early and highly treatable stage.
      Because paraneoplastic syndromes often cause considerable morbidity, effective
      treatment can improve patient quality of life, enhance the delivery of cancer
      therapy, and prolong survival. Treatments include addressing the underlying
      malignancy, immunosuppression (for neurologic, dermatologic, and rheumatologic
      paraneoplastic syndromes), and correction of electrolyte and hormonal
      derangements (for endocrine paraneoplastic syndromes). This review focuses on the
      diagnosis and treatment of paraneoplastic syndromes, with emphasis on those most
      frequently encountered clinically. Initial literature searches for this review
      were conducted using PubMed and the keyword paraneoplastic in conjunction with
      keywords such as malignancy, SIADH, and limbic encephalitis, depending on the
      particular topic. Date limitations typically were not used, but preference was
      given to recent articles when possible.

PMID- 20810798
TI  - A big man with a broken heart: stress-induced cardiomyopathy in a morbidly obese
      man.

PMID- 20810799
TI  - Tailoring diagnosis and management of pericardial disease to the epidemiological
      setting.

PMID- 20810800
TI  - Bullous leg lesions caused by culicoides midges after travel in the Amazon basin.

PMID- 20810801
TI  - Chromoblastomycosis in Western Thailand.

PMID- 20810802
TI  - Developing the right pneumococcal vaccine for the time and place.

PMID- 20810803
TI  - Enhanced determination of Streptococcus pneumoniae serotypes associated with
      invasive disease in Laos by using a real-time polymerase chain reaction
      serotyping assay with cerebrospinal fluid.
AB  - A prospective hospital-based study was undertaken to define the incidence of
      invasive pneumococcal disease (IPD) and circulating serotypes in Laos. Of 10,799
      patients with hemocultures and 353 patients with cerebrospinal fluid samples,
      0.21% and 5.4%, respectively, were positive for Streptococcus pneumoniae, giving
      a total of 35 IPD patients. We developed a real-time polymerase chain reaction to
      detect serotypes represented in the 13-valent pneumococcal vaccine. A blinded
      evaluation comparing serotype as defined by the Quellung reaction versus the
      polymerase chain reaction demonstrated 100% concordance. The most frequent
      serotype (n = 33 patients) was 1 (n = 6), followed by serotypes 5, 6A/B/C, 14,
      and 23F. Serotypes represented in the 7-valent polysaccharide-protein conjugate
      vaccine (PCV-7) infected 39% of patients, with 73% coverage for the PCV-10 and
      PCV-13 vaccines. Although the sample size is small, these data suggest that the
      PCV-7 vaccine may have relatively low efficacy in Laos. Further studies are
      urgently needed to guide pneumococcal vaccine policy in Laos.

PMID- 20810804
TI  - Evaluation of recurrent parasitemia after artemether-lumefantrine treatment for
      uncomplicated malaria in children in western Kenya.
AB  - From April 2005 to April 2006, a phase 2 malaria vaccine trial in Kenya enrolled
      400 children aged 12-47 months. Each received mixed supervised and unsupervised
      artemether-lumefantrine for uncomplicated malaria, using a standard six-dose
      regimen, by weight. Children were followed for detection of parasitemia and
      clinical malaria. A median of two negative malaria blood films occurred during
      every recurrent parasitemia (RP) episode, suggesting reinfection over late
      recrudescence. Median time to RP after starting artemether-lumefantrine was 37
      days (36-38). Of 2,020 evaluable artemether-lumefantrine treatments, there were
      no RPs in 99% by day 14, 71% by day 28, and 41% by day 42. By World Health
      Organization standards, 71% of treatment courses had adequate responses. Although
      recrudescence in some cannot be ruled out, our cohort had a shorter median time
      to RP compared with other artemether-lumefantrine treatment studies. This
      underscores patient counseling on completing all treatment doses for optimal
      protection from RP.

PMID- 20810805
TI  - Malaria incidence and prevalence among children living in a peri-urban area on
      the coast of benin, west Africa: a longitudinal study.
AB  - Clinical malaria incidence was determined over 18 months in a cohort of 553
      children living in a peri-urban area near Cotonou. Three cross-sectional surveys
      were also carried out. Malaria incidence showed a marked seasonal distribution
      with two peaks: the first corresponding to the long rainy season, and the second
      corresponding to the overflowing of Lake Nokoue. The overall Plasmodium
      falciparum incidence rate was estimated at 84/1,000 person-months, and its
      prevalence was estimated at over 40% in the two first surveys and 68.9% in the
      third survey. Multivariate analysis showed that girls and people living in closed
      houses had a lower risk of clinical malaria. Bed net use was associated with a
      lower risk of malaria infection. Conversely, children of families owing a pirogue
      were at higher risk of clinical malaria. Considering the high pyrethroids
      resistance, indoor residual spraying with either a carbamate or an organophospate
      insecticide may have a major impact on the malaria burden.

PMID- 20810807
TI  - Scaling up malaria control in Zambia: progress and impact 2005-2008.
AB  - Zambia national survey, administrative, health facility, and special study data
      were used to assess progress and impact in national malaria control between 2000
      and 2008. Zambia malaria financial support expanded from US$9 million in 2003 to
      US$ approximately 40 million in 2008. High malaria prevention coverage was
      achieved and extended to poor and rural areas. Increasing coverage was consistent
      in time and location with reductions in child (age 6-59 months) parasitemia and
      severe anemia (53% and 68% reductions, respectively, from 2006 to 2008) and with
      lower post-neonatal infant and 1-4 years of age child mortality (38% and 36%
      reductions between 2001/2 and 2007 survey estimates). Zambia has dramatically
      reduced malaria transmission, disease, and child mortality burden through rapid
      national scale-up of effective interventions. Sustained progress toward malaria
      elimination will require maintaining high prevention coverage and further
      reducing transmission by actively searching for and treating infected people who
      harbor malaria parasites.

PMID- 20810806
TI  - Mutations in the antifolate-resistance-associated genes dihydrofolate reductase
      and dihydropteroate synthase in Plasmodium vivax isolates from malaria-endemic
      countries.
AB  - Parasite dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) are
      known target enzymes of antifolate drugs used for the treatment and prophylaxis
      of persons with malaria. We sequenced the Plasmodium vivax dihydrofolate
      reductase (pvdhfr) and dihydropteroate synthase (pvdhps) genes to examine the
      prevalence and extent of point mutations in isolates from malaria-endemic
      countries. Double mutations (S58R and S117N) or quadruple mutations (F57L/I,
      S58R, T61M, and S117T) in the pvdhfr gene were found in isolates from Thailand
      (96.4%) and Myanmar (71.4%), but in only one isolate (1.0%) from Korea, where
      sulfadoxine-pyrimethamine has never been used. The pvdhfr point mutations
      correlated strongly with the pvdhps point mutations and ranged from single to
      triple mutations (S382A, A383G, and A553G), among isolates from Thailand,
      Myanmar, and Korea. These findings suggests that the prevalence of mutations in
      pvdhfr and pvdhps in P. vivax isolates from different malaria-endemic countries
      is associated with selection pressure imposed by sulfadoxine-pyrimethamine.

PMID- 20810808
TI  - A comparison of methods to detect and quantify the markers of antimalarial drug
      resistance.
AB  - We compare, contrast, and evaluate methods to quantify genetic markers of
      antimalarial drug resistance. Frequency estimates should be reported along with
      crude prevalence. There are four main potential methods to estimate frequencies
      in blood samples: simple counting of single nucleotide polymorphisms (SNPs) and
      haplotypes in samples with multiplicity of infection (MOI) = 1; SNP counting in
      samples with MOI < or = 2; SNP and haplotypes counting in samples with
      unambiguous genotypes; statistical inference using SNP and MOI data from all
      samples. Large differences between the methods became apparent when analyzing
      field data with high MOI. Simple counting dramatically reduced sample size and
      estimate precision, and we show that analysis of unambiguous samples is biased,
      leaving maximum likelihood or similar statistical inference as the only practical
      option. It is essential to account for genotyping missing minor clones; ignoring
      this phenomenon resulted in a 2-fold underestimation of SNPs and haplotypes
      present at low frequencies.

PMID- 20810809
TI  - Rapid detection of lactate dehydrogenase and genotyping of Plasmodium falciparum
      in saliva of children with acute uncomplicated malaria.
AB  - The diagnosis of malaria in biological fluids other than blood using non
      invasive, rapid diagnostic techniques provides a valuable approach in case
      management and epidemiological studies of malaria. Rapid detection of Plasmodium
      falciparum lactate dehydrogenase (pLDH) in saliva samples from 130 of 144
      children with microscopically confirmed P. falciparum infection was evaluated
      using Optimal-IT dipsticks. Genotyping of parasites was also performed in saliva
      and blood samples from a cohort of patients by polymerase chain reaction (PCR).
      The sensitivity of the dipstick in whole-blood, whole-saliva, or supernatant of
      spun saliva samples was 97.2%, 77.9%, and 48.4%, respectively. The sensitivity of
      the dipstick in whole-saliva samples was significantly higher than in supernatant
      of spun saliva samples (P < 0.0005). Mutant T76 allele was detectable in 60% and
      57% of blood and saliva samples, respectively. This finding shows rapid detection
      of pLDH in patient saliva.

PMID- 20810810
TI  - Asymptomatic infection with visceral leishmaniasis in a disease-endemic area in
      bihar, India.
AB  - A prospective study was carried out in a cohort of 355 persons in a leishmaniasis
      endemic village of the Patna District in Bihar, India, to determine the
      prevalence of asymptomatic persons and rate of progression to symptomatic
      visceral leishmaniasis (VL) cases. At baseline screening, 50 persons were
      positive for leishmaniasis by any of the three tests (rK39 strip test, direct
      agglutination test, and polymerase chain reaction) used. Point prevalence of
      asymptomatic VL was 110 per 1,000 persons and the rate of progression to
      symptomatic cases was 17.85 per 1,000 person-months. The incidence rate ratio of
      progression to symptomatic case was 3.36 (95% confidence interval [CI] = 0.75
      15.01, P = 0.09) among case-contacts of VL compared with neighbors. High
      prevalence of asymptomatic persons and clinical VL cases and high density of
      Phlebotomus argentipes sand flies can lead to transmission of VL in VL-endemic
      areas.

PMID- 20810811
TI  - Effectiveness and feasibility of active and passive case detection in the
      visceral leishmaniasis elimination initiative in India, Bangladesh, and Nepal.
AB  - This study analyzed the effectiveness of active case detection (ACD) for new
      visceral leishmaniasis (VL) cases. ACD detection was carried out using house to
      house screening in Bangladesh and India and by neighborhood screening around
      index cases in Nepal. The percent increase of new VL cases through ACD compared
      to PCD was 6.7-17.1% in India; 38.8% in Nepal; and 60% in Bangladesh. The
      screening effort was high in India and Bangladesh (house to house screening)
      compared to Nepal (index case screening). The additional cost per new VL case
      detected varied: $50 to $106 in India; $172 in Bangladesh; $262 in Nepal
      depending on the type of screening staff, transport and training costs. The
      estimated annual VL incidence in the ACD arm ranged from 315-383 in India; 109 in
      Bangladesh, and 43 per 100,000 in Nepal. The additional effort and cost rises as
      disease incidence declines or PCD improves.

PMID- 20810812
TI  - Lack of protection of pre-immunization with saliva of long-term colonized
      Phlebotomus papatasi against experimental challenge with Leishmania major and
      saliva of wild-caught P. papatasi.
AB  - Immunity to saliva of Phlebotomus papatasi protects against Leishmania major
      infection as determined by co-inoculation of parasites with salivary gland
      homogenates (SGHs) of this vector. These results were obtained with long-term
      colonized female P. papatasi. We investigated the effect of pre-immunization with
      SGH of long-term colonized P. papatasi against L. major infection co-inoculated
      with SGH of wild-caught P. papatasi. Our results showed that pre-exposure to SGH
      of long-term, colonized P. papatasi do not confer protection against infection
      with L. major co-inoculated with SGH of wild-caught P. papatasi. These
      preliminary results strongly suggest that the effectiveness of a vector saliva
      based vaccine derived from colonized sand fly populations may be affected by
      inconsistent immune response after natural exposure.

PMID- 20810813
TI  - Mucosal leishmaniasis and abnormalities on computed tomographic scans of
      paranasal sinuses.
AB  - Studies evaluating radiologic aspects, local complications, and structural
      alterations of the paranasal sinus in patients with mucosal leishmaniasis (ML)
      are lacking. The aim of this study was to analyze alterations of the paranasal
      sinuses in patients with ML by using computed tomography (CT) scans. This
      prospective study evaluated 26 patients in Brazil with ML from December 2008
      through June 2009. All patients underwent CT scans of the paranasal sinuses.
      Paranasal thickening was observed in 25 patients (96%). Nasal perforation was
      observed in 17 patients (65%). Those patients who received re-treatment showed
      more abnormalities on CT scan than cured patients (P < 0.05). Complications of ML
      are not limited to the nasal mucosa but extend to the paranasal sinuses. Mucosal
      thickening, opacified air cells, bony remodeling, and bony thickening caused by
      inflammatory osteitis of the sinus cavity walls are CT findings suggestive of
      chronic sinusitis.

PMID- 20810814
TI  - Infectivity, pathogenicity, and virulence of Trypanosoma cruzi Isolates from
      sylvatic animals and vectors, and domestic dogs from the United States in ICR
      strain mice and SD strain rats.
AB  - Trypanosoma cruzi, the causative agent of Chagas disease, is widespread in the
      southern United States. In addition to detection in numerous wildlife host
      species, cases have been diagnosed in domestic dogs and humans. In the current
      investigation, groups of laboratory mice [Crl:CD1 (ICR)] were inoculated with one
      of 18 United States T. cruzi isolates obtained from a wide host range to
      elucidate their infectivity, pathogenicity, and virulence. In addition,
      laboratory rats (SD strain) were inoculated with four isolates. Mice and rats
      were susceptible to infection with all strains, but no morbidity or mortality was
      noted, which indicates that these T. cruzi isolates from the United States had
      low virulence for laboratory mice and rats.

PMID- 20810815
TI  - Giardiasis and poor vitamin A status among aboriginal school children in rural
      Malaysia.
AB  - A cross-sectional study was carried out on 241 primary schoolchildren in Pahang,
      Malaysia to update their vitamin A status and to investigate the association of
      poor vitamin A status with their health and socioeconomic factors. All children
      were screened for intestinal parasitic infections. Blood samples were collected
      and vitamin A status was assessed. Socioeconomic data were collected by using pre
      tested questionnaires. The results showed that 66 (27.4%) children had low serum
      retinol levels (< 0.70 micromol/L). Giardiasis and severe ascariasis were
      significantly associated with low serum retinol levels (P = 0.004 and P = 0.018,
      respectively). Logistic regression confirmed the significant association of
      giardiasis with low serum retinol (odds ratio = 2.7, 95% confidence interval =
      1.3-5.5). In conclusion, vitamin A deficiency is still a public health problem in
      rural Malaysia. Vitamin A supplementation and treatment of intestinal parasitic
      infections should be distributed periodically to these children to improve their
      health and nutritional status.

PMID- 20810816
TI  - Prevalence and risk factors of toxoplasmosis among pregnant women in Fortaleza,
      Northeastern Brazil.
AB  - We determined the seroprevalence of Toxoplasma gondii and associated risk factors
      among 963 pregnant women attending an obstetric hospital in Fortaleza, Brazil.
      Seroprevalences of IgG and IgM against T. gondii were 68.6% (95% confidence
      interval [CI] = 65.6-71.6%) and 0.5% (95% CI = 0.06-1.0%), respectively.
      Seroprevalence of IgG was high in women less than 25 years of age (91.7%) and in
      low-income women (odds Ratio [OR] = 1.40, 95% CI = 1.02-1.90). Multivariate
      regression analysis showed that consumption of homemade water ice (adjusted OR =
      1.49, 95% CI = 1.09-2.04), vegetables washed with untreated water (adjusted OR =
      1.43, 95% CI = 1.05-1.94), consumption of chicken (adjusted OR = 1.49, 95% CI =
      1.12-2.0), and dog ownership (adjusted OR= 1.46, 95% CI = 1.07-1.98) were factors
      associated with IgG seropositivity. Young women in northeastern Brazil living
      under poor socioeconomic conditions are at highest risk for acquiring infection
      with T. gondii. Oocyst contamination of water and soil must be addressed in
      future prevention strategies.

PMID- 20810817
TI  - Effects of annual mass treatment with ivermectin for onchocerciasis on the
      prevalence of intestinal helminths.
AB  - We evaluated the effect of annual ivermectin (IV) distribution for onchocerciasis
      on the prevalence of soil transmitted helminth (STH) infections in school-aged
      (SAC) and preschool-aged (PAC) children by comparing children in villages that
      had received treatment for 13 years to those from socioeconomically similar
      villages in untreated areas. We enrolled 1,031 SAC and 211 PAC for Kato Katz
      examinations. Treated areas had a lower prevalence of Ascaris (SAC: 3% versus
      12%, P < 0.0001; PAC: 3% versus 10%, P < 0.051) and Trichuris (SAC: 6% versus
      10%, P = 0.012; PAC: 1% versus 8%, P = 0.019), but not hookworm (SAC: 38% versus
      42%, P = 0.20; PAC: 21% versus 27%, P = 0.30). The prevalence of Ascaris or
      Trichuris in treated areas was below the WHO threshold for mass antihelminthic
      treatment (MDA), but not for hookworm. We conclude that benzimidazole MDA in IV
      treatment areas is indicated to effectively control hookworm.

PMID- 20810818
TI  - Detection of early and single infections of Schistosoma japonicum in the
      intermediate host snail, Oncomelania hupensis, by PCR and loop-mediated
      isothermal amplification (LAMP) assay.
AB  - Polymerase chain reaction (PCR) with the specific primer set amplifying 28S
      ribosomal DNA (rDNA) of Schistosoma japonicum was able to detect genomic DNA of
      S. japonicum, but not S. mansoni, at 100 fg. This procedure enabled us to detect
      the DNA from a single miracidium and a snail infected with one miracidium at just
      1 day after infection. We compared these results with those from loop-mediated
      isothermal amplification (LAMP) targeting 28S rDNA and found similar results. The
      LAMP could amplify the specific DNA from a group of 100 normal snails mixed with
      one infected snail A PCR screening of infected snails from endemic regions in
      Anhui Province revealed schistosomal DNA even in snails found negative by
      microscopy. PCR and LAMP show promise for monitoring the early infection rate in
      snails, and they may be useful for predicting the risk of infection in the
      endemic places.

PMID- 20810819
TI  - Hookworm (Necator americanus) larval enzymes disrupt human vascular endothelium.
AB  - Knowledge of the molecular mechanisms used by Necator americanus larvae to
      penetrate the human skin and the vasculature would aid the development of
      effective vaccines against this important pathogen. In this work, the impact of
      N. americanus exsheathing fluid (EF) and excretory/secretory products (ES) on the
      endothelial barrier was examined using human umbilical vein endothelial cells
      (HUVEC). Cellular responses were assessed by investigating molecular changes at
      cell-cell junctions and by determining levels of secreted IL-6, IL-8, and
      vascular endothelial growth factor (VEGF) in the culture medium. It would appear
      that a repertoire of larval proteases caused a dose-related increase in
      endothelial permeability as characterized by a decrease in monolayer resistance
      with increased permeation of tracer-albumin. These barrier changes were
      associated with disruption of junctional vascular endothelial cadherin (VE
      cadherin) and F-actin and an increase in endothelial secretion of IL-6 and IL-8.
      Our data suggest that larval proteases play an important role in negotiating the
      endothelium.

PMID- 20810820
TI  - Nutritional status of children after a food-supplementation program integrated
      with routine health care through mobile clinics in migrant communities in the
      Dominican Republic.
AB  - The objective of this study was to compare acute and chronic undernutrition rates
      before and after the introduction of a food-supplementation program as an adjunct
      to routine health care for children of migrant workers in the Dominican Republic.
      The cross-sectional study was conducted in five rural communities in the
      Dominican Republic. Children 18 years and younger were eligible if they received
      routine health care from local mobile clinics. Data were obtained before (2005)
      and after (2006) initiation of a food-supplementation program. chi(2) or Fisher
      exact tests were used for analysis. Among 175 children in 2005, 52% were female,
      and 59% were < 5 years of age (mean age = 5.3 years). Among 148 children in 2006,
      48% were female, and 57% were < 5 years of age (mean age = 5.6 years). Acute
      undernutrition rates decreased from 40% to 23% (P = 0.001) after initiation of
      the food-supplementation program. Rates of chronic undernutrition decreased from
      33% to 18% after the initiation of the food-supplementation program (P = 0.003).
      Food supplementation in the context of routine health-care visits improved the
      nutritional status of children, and it warrants further exploration as a way to
      reduce childhood undernutrition in resource-scarce areas.

PMID- 20810821
TI  - Implementation of a validated peripheral neuropathy screening tool in patients
      receiving antiretroviral therapy in Mombasa, Kenya.
AB  - Limited objective data are available for the prevalence of peripheral neuropathy
      (PN) among antiretroviral (ART)-treated human immunodeficiency virus (HIV)
      infected patients in resource-limited settings. A validated neuropathy-screening
      tool was integrated into routine ART visits at an HIV clinic in Mombasa, Kenya.
      Diagnosis of PN required at least one symptom and either abnormal vibratory
      sensation or deep tendon reflex bilaterally. Among 102 consecutively screened
      patients, 63% were women, 62% were receiving ART for < or = 1 year, and 86% were
      receiving a stavudine (D4T)-based regimen. Thirty-seven (36%) had PN. Univariate
      analysis showed that current D4T use was protective against PN (P = 0.03) and
      older age was a marginal risk factor (P = 0.05). Multivariate analysis showed
      that older age was a risk factor for neuropathy (P = 0.04). Peripheral neuropathy
      was common, particularly among older HIV-infected adults in Kenya. The protective
      association with current D4T use likely represents survivor effect bias.
      Longitudinal studies using this screen will help further characterize PN in
      resource-limited settings.

PMID- 20810822
TI  - The current availability of antiepileptic drugs in Zambia: implications for the
      ILAE/WHO "out of the shadows" campaign.
AB  - Recent concerns regarding antiepileptic drug (AED) availability in Zambia led us
      to conduct a study in the Lusaka and Southern Provinces to quantify the
      availability and cost of AEDs and assess determinants. Among 111 pharmacies,
      almost one-half did not carry AEDs (N = 54; 49.1%). Available AEDs were
      phenobarbitone (21; 18.9%), carbamazepine (27; 24.3%), valproic acid (4; 3.6%),
      and phenytoin (3; 2.7%). Adult out-of-pocket monthly costs ranged from US $7 to
      $30. Pediatric syrups were universally unavailable. Interviews revealed several
      barriers to AED provision, including that handling phenobarbitone (historically
      the most affordable AED) has become increasingly difficult because of newly
      enforced regulatory requirements. Personal communications with epilepsy-care
      providers in other low income countries suggest that this problem may be
      widespread. Improved enforcement of existing drug regulations may be contributing
      to the AED shortage. Social programs aimed at encouraging people with epilepsy to
      come "out of the shadows" must be preceded by improved AED access.

PMID- 20810823
TI  - A survey of the management, control, and complications of diabetes mellitus in
      patients attending a diabetes clinic in Blantyre, Malawi, an area of high HIV
      prevalence.
AB  - The aim of this study was to describe the current status of diabetes care in an
      urban diabetes clinic in Malawi and the prevalence of human immunodeficiency
      virus (HIV) in this population, investigating possible associations between HIV
      and diabetes. A systematic prospective survey of patients attending the diabetes
      clinic at a teaching hospital in Blantyre, Malawi was conducted. Six hundred
      twenty patients were assessed. Seventy-four percent had glycosylated hemoglobin
      (HbA1C) > 7.5%. Systolic blood pressure was > 140 mm Hg in 52% of patients.
      Hypertension was more common in patients with raised creatinine (P < 0.003),
      retinopathy (P = 0.01), and stroke (P < 0.0002). Microvascular complication rates
      were high, specifically nephropathy (34.7%), retinopathy (34.7%), and neuropathy
      (46.4%). HIV seroprevalence was 13.7%. HIV-positive subjects had a lower body
      mass index (BMI) and lower fasting blood sugar, and they were more likely to have
      albuminuria (48.0% versus 33.3%; P < 0.05). Control of glycemia and hypertension
      were poor, and microvascular complications were common. Nephropathy in diabetic
      patients may be affected by HIV status.

PMID- 20810824
TI  - A systematic review and meta-analysis of the association between self-reported
      diarrheal disease and distance from home to water source.
AB  - The aim of this study was to identify whether there was a relationship between
      the distance that people have to carry water home and ill health. We conducted a
      systematic review for papers that reported on the association between diarrheal
      risk and distance. Six papers were identified for inclusion in the meta-analysis.
      These were all observational studies, and only two reported effect sizes that
      adjusted for possible confounding. Multiple different types of water sources
      supplied the study communities. The combined odds ratio (OR) showed a significant
      increase in illness risk in people living farther away from their water source
      (OR = 1.45; 95% confidence interval [CI] = 1.04-1.68). There is a need for better
      designed studies to further elucidate the health impacts on having to carry water
      home.

PMID- 20810825
TI  - Genetic structure of Anopheles (Nyssorhynchus) marajoara (Diptera: Culicidae) in
      Colombia.
AB  - Five Anopheles marajoara Galvao and Damasceno populations, representing diverse
      ecological conditions, were sampled throughout Colombia and analyzed using nine
      hypervariable DNA microsatellite loci. The overall genetic diversity (H = 0.58)
      was lower than that determined for some Brazilian populations using the same
      markers. The Caqueta population (Colombia) had the lowest gene diversity (H =
      0.48), and it was the only population at Hardy-Weinberg equilibrium. Hardy
      Weinberg disequilibrium in the remaining four populations was probably caused by
      the Wahlund effect. The assignment analyses showed two incompletely isolated gene
      pools separated by the Eastern Andean cordillera. However, other possible
      geographical barriers (rivers and other mountains) did not play any role in the
      moderate genetic heterogeneity found among these populations (F(ST) = 0.069).
      These results are noteworthy, because this species is a putative malaria vector
      in Colombia.

PMID- 20810826
TI  - An exposure-free tool for monitoring adult malaria mosquito populations.
AB  - Catches of Anopheles gambiae and An. arabiensis with the Ifakara Tent Trap-model
      B (ITT-B) correlate better with human landing catches than any other method but
      fail to reduce the proportion of blood-fed mosquito caught, which indicates that
      users are exposed to bites during collection. An improved C model (ITT-C) was
      developed and evaluated by comparing with ITT-B in semi-field and full-field
      conditions in southern Tanzania. The sensitivity of the ITT-C was approximately
      two times that of the ITT-B: relative rate (95% confidence interval) = 1.92 (1.52
      2.42), 1.90 (1.48-2.43), and 2.30 (1.54-3.30) for field populations of An.
      arabiensis, Culex spp., and Mansonia spp., respectively. The ITT-C caught 73%
      less blood-fed An. arabiensis than the ITT-B in open field experiments and none
      in semi-field experiments, which confirmed that the C design is a safe trapping
      method. Validation of ITT-C by comparison with human landing catches and
      parasitologic measures of human infection status may be necessary to confirm that
      this design produces consistent and epidemiologically meaningful results.

PMID- 20810827
TI  - Aestivation of the African malaria mosquito, Anopheles gambiae in the Sahel.
AB  - The African malaria mosquito, Anopheles gambiae, inhabits diverse environments
      including dry savannas, where surface waters required for larval development are
      absent for 4-8 months per year. Under such conditions, An. gambiae virtually
      disappears. Whether populations survive the long dry season by aestivation (a
      dormant state promoting extended longevity during the summer) or are
      reestablished by migrants from distant locations where larval sites persist has
      remained an enigma for over 60 years. Resolving this question is important,
      because fragile dry season populations may be more susceptible to control. Here,
      we show unequivocally that An. gambiae aestivates based on a demographic study
      and a mark release-recapture experiment spanning the period from the end of one
      wet season to the beginning of the next. During the dry season, An. gambiae was
      barely detectable in Sahelian villages of Mali. Five days after the first rain,
      before a new generation of adults could be produced, mosquito abundance surged 10
      fold, implying that most mosquitoes were concealed locally until the rain. Four
      days after the first rain, a marked female An. gambiae s.s. was recaptured.
      Initially captured, marked, and released at the end of the previous wet season,
      she has survived the 7-month-long dry season. These results provide evidence that
      An. gambiae persists throughout the dry season by aestivation and open new
      questions for mosquito and parasite research. Improved malaria control by
      targeting aestivating mosquitoes using existing or novel strategies may be
      possible.

PMID- 20810828
TI  - Spatial and temporal variation in vector competence of Culex pipiens and Cx.
      restuans mosquitoes for West Nile virus.
AB  - Vector competence, the probability that a vector will transmit a pathogen after
      feeding on an infected host, is known to vary among vector species, populations,
      days since feeding, and temperature during the extrinsic incubation period.
      However, the extent of spatio-temporal variability and consistency in vector
      competence of populations is not known. We examined vector competence of Culex
      pipiens Linnaeus and Cx. restuans Theobald mosquitoes for West Nile virus
      collected over 3 years from 17 sites to measure spatial and temporal scales of
      variation in vector competence. We found extreme variation with 0-52% of
      mosquitoes transmitting West Nile virus at a single site between different
      sampling periods, and similar variation across populations. However, we also
      found that within a smaller geographic range, vector competence varied somewhat
      synchronously, suggesting that environmental and population genetic factors might
      influence vector competence. These results highlight the spatio-temporal
      variability in vector competence and the role of local processes.

PMID- 20810829
TI  - A recombinant AeDNA containing the insect-specific toxin, BmK IT1, displayed an
      increasing pathogenicity on Aedes albopictus.
AB  - The Aedes aegypti densovirus (AeDNV) has previously shown potential in mosquito
      control. To improve its efficacy as a biopesticide, the gene for an excitatory
      insect-specific toxin from Buthus martensii Karsch (BmK IT1) was inserted into
      the AeDNV genome and cloned into pUCA plasmid. The coding sequence for green
      fluorescent protein was ligated to the C-terminus of the BmK IT1 gene as a
      screening marker. Recombinant and helper plasmids were cotransfected into C6/36
      cells; wild-type viruses were the controls. The recombinant viruses were
      identified and quantified by real-time polymerase chain reaction and exposed to
      Ae. albopictus larvae for the evaluation of its bioinsecticidal activity. LT(50)
      and LD(50) bioassays showed that the recombinant AeDNV had stronger and faster
      pathogenic effects on Ae. albopictus than the wild-type virus. This is the first
      report on the recombinant AeDNA containing the insect-specific toxin, BmK IT1,
      which may be used to develop a novel type of insecticide.

PMID- 20810830
TI  - Interannual variability of human plague occurrence in the Western United States
      explained by tropical and North Pacific Ocean climate variability.
AB  - Plague is a vector-borne, highly virulent zoonotic disease caused by the
      bacterium Yersinia pestis. It persists in nature through transmission between its
      hosts (wild rodents) and vectors (fleas). During epizootics, the disease expands
      and spills over to other host species such as humans living in or close to
      affected areas. Here, we investigate the effect of large-scale climate
      variability on the dynamics of human plague in the western United States using a
      56-year time series of plague reports (1950-2005). We found that El Nino Southern
      Oscillation and Pacific Decadal Oscillation in combination affect the dynamics of
      human plague over the western United States. The underlying mechanism could
      involve changes in precipitation and temperatures that impact both hosts and
      vectors. It is suggested that snow also may play a key role, possibly through its
      effects on summer soil moisture, which is known to be instrumental for flea
      survival and development and sustained growth of vegetation for rodents.

PMID- 20810831
TI  - Risk factors for clinical leptospirosis from Western Jamaica.
AB  - A retrospective, matched case-control study was conducted in Jamaica's Western
      Regional Health Authority (WRHA). Forty-three individuals developing clinical
      leptospirosis between January 2005 and December 2007 (i.e., cases) were age and
      neighborhood matched to 89 controls. Odds ratios (OR) and associated 95%
      confidence intervals (CIs) and the relative excess risk due to interaction (RERI)
      were calculated. Cases had increased odds of contact with rodents OR 3.52, goats
      OR 3.38, and being engaged in outdoor labor OR 5.30. Knowledge of leptospirosis
      and indoor work was protective, OR 0.39 and OR 0.16, respectively. Positive RERI
      values were noted for joint exposure to rodents and goats (RERI 5.54), outdoor
      labor and goats (RERI 6.97), and outdoor labor and rodents (RERI 30.59). Our
      results suggest a synergistic effect of occupational and environmental exposures
      on clinical human leptospirosis from the WRHA. Knowledge of the disease and its
      risk factors allows for protection from the disease.

PMID- 20810832
TI  - Reactions following completion of 1 and 2 year multidrug therapy (MDT).
AB  - We evaluated the incidence, severity, and duration of reactional states in 139
      multibacillary (MB) leprosy patients in the first 2 years after the completion of
      the 1 year regimen of multidrug therapy (MDT) currently recommended by the World
      Health Organization (WHO) and compared those findings with 295 MB leprosy
      patients treated with the same regimen previously recommended for 2 years. During
      the first year after the completion of 1 year MDT, patients experienced 1 or more
      reactional states 27% of the time, the vast majority being lepra type 1 reactions
      (reversal reactions, RR), whereas patients who received 2 year MDT experienced a
      reactional state during that time period only 8% of the time (P < 0.001).
      Furthermore, during the first year after the completion of therapy, and during
      the first 2 years, both the number of reactional states and reversal reactions
      were significantly (P < or = 0.004) more frequent, severe, of longer duration,
      and more commonly associated with neuritis.

PMID- 20810833
TI  - Transmission dynamics of Francisella tularensis subspecies and clades by nymphal
      Dermacentor variabilis (Acari: Ixodidae).
AB  - In the United States, the American dog tick, Dermacentor variabilis (Say) is
      considered an important biological vector of Francisella tularensis, the
      etiologic agent of tularemia. In this study, we evaluated the vector efficiency
      of nymphal D. variabilis infected as larvae with differing clades and subspecies
      (A1b, A2, and type B) of F. tularensis. In all cases, D. variabilis larvae were
      able to acquire, maintain, and transstadially transmit F. tularensis. Significant
      replication of the bacteria also occurred in infected nymphs. Transmission of F.
      tularensis to Swiss Webster mice was not observed with A1b, and low rates were
      observed with A2 (8.0%) and type B (13.5%). Negative effects on tick survivorship
      were also observed for A1b, A2, and type B infections. Our results provide
      evidence of a high fitness cost and low transmission rates during the immature
      stages, suggesting that D. variabilis may play a limited role in enzootic
      maintenance of F. tularensis.

PMID- 20810834
TI  - Absence of Rickettsia rickettsii and occurrence of other spotted fever group
      rickettsiae in ticks from Tennessee.
AB  - Rocky Mountain spotted fever (RMSF) is the most common tick-borne illness in
      Tennessee. Little is known about the occurrence of R. rickettsii, the causative
      agent, in ticks in Tennessee. To better understand the prevalence and
      distribution of rickettsial agents in ticks, we tested 1,265 Amblyomma,
      Dermacentor, and Ixodes adult and nymphal ticks. Additionally, we tested 231
      Amblyomma americanum larvae. Ticks were collected from 49 counties from humans,
      wild animals, domestic canines, and flannel drags. Spotted fever group
      rickettsiae (SFGR) DNA was detected by polymerase chain reaction (PCR) in 32% of
      adult and nymphal ticks. A total minimum infection rate of 85.63 was found in
      larval pools tested. Three rickettsial species, Rickettsia montana, Rickettsia
      amblyommii, and Rickettsia cooleyi were identified by molecular analysis.
      Rickettsia rickettsii was not detected. This study suggests that some RMSF cases
      reported in Tennessee may be caused by cross-reactivity with other SFGR
      antigenically related to R. rickettsii.

PMID- 20810835
TI  - Phylogenetic analysis of 56-kDa type-specific antigen gene of Orientia
      tsutsugamushi isolates in Taiwan.
AB  - Scrub typhus is a rickettsial disease transmitted to humans through the bite of
      chigger mites infected with Orientia tsutsugamushi, and is an endemic disease in
      Taiwan. To elucidate the molecular epidemiology of O. tsutsugamushi, the complete
      open reading frame of the 56-kDa type-specific antigen gene sequence of strains
      isolated from scrub typhus patients were determined and analyzed. A total of 116
      isolates of O. tsutsugamushi were successfully isolated from patients infected in
      diverse geographic origins including Taiwan and three offshore islets, Kinmen,
      Matsu, and Penghu between May 2006 and December 2007. Sequence analysis revealed
      that 22 distinct sequence types could be identified that were broadly distributed
      in different clusters of the phylogenetic tree. Most of the isolates belong to
      Karp, Kawasaki, and Kuroki genotypes and are closely related to strains from
      Thailand, Japan, and Korea, whereas unique isolates different from other
      countries were also found in Taiwan. Distinct seasonal distributions were found
      in different sequence types. Some sequence types caused disease in the cold
      season, whereas others caused disease in the warm season.

PMID- 20810836
TI  - Dengue Fever in mainland China.
AB  - Dengue is an acute emerging infectious disease transmitted by Aedes mosquitoes
      and has become a serious global public health problem. In mainland China, a
      number of large dengue outbreaks with serious consequences have been reported as
      early as 1978. In the three decades from 1978 to 2008, a total of 655,324 cases
      were reported, resulting in 610 deaths. Since the 1990s, dengue epidemics have
      spread gradually from Guangdong, Hainan, and Guangxi provinces in the southern
      coastal regions to the relatively northern and western regions including Fujian,
      Zhejiang, and Yunnan provinces. As the major transmission vectors of dengue
      viruses, the biological behavior and vectorial capacity of Aedes mosquitoes have
      undergone significant changes in the last two decades in mainland China, most
      likely the result of urbanization and global climate changes. In this review, we
      summarize the geographic and temporal distributions, the serotype and genotype
      distributions of dengue viruses in mainland China, and analyze the current status
      of surveillance and control of vectors for dengue transmission.

PMID- 20810837
TI  - Prolonged co-circulation of two distinct Dengue virus Type 3 lineages in the
      hyperendemic area of Medellin, Colombia.
AB  - During the past two decades, Dengue virus-3 (DENV-3) has re-emerged in the
      Western Hemisphere causing significant epidemics of dengue fever (DF) and dengue
      hemorrhagic fever (DHF). In an effort to understand the molecular evolution of
      DENV-3 and their relationships to other DENV-3 circulating in the western
      hemisphere, we conducted a phylogenetic study on DENV-3 isolates made between
      2002 and 2007 in the metropolitan area of Medellin, Colombia. An unexpected co
      circulation of two different variants of DENV-3 subtype III during at least 5
      years in Medellin was found. In addition, a more complete analysis of DENV-3
      viruses isolated in other South American regions revealed the existence of three
      different subtype III lineages, all derived from independent introductions. This
      study documents significant genetic diversity of circulating viruses within the
      same subtype and an unusual capacity of the population of this city to support
      continuous circulation of multiple variants of dengue virus.

PMID- 20810838
TI  - Fatal Staphylococcal infection following classic Dengue fever.
AB  - Dengue represents an important public health issue in many tropical areas,
      leading to high morbidity and the employment of substantial health resources.
      Even though the number of fatalities related to dengue is unknown, several
      reports warn about the potential occurrence of severe infections and even death.
      The clinical spectrum of dengue is highly variable, ranging from a mild flu-like
      syndrome to severe disease, with shock and hemorrhage. The occurrence of
      bacterial superinfection, or coinfection, in patients with dengue has been noted
      by some authors, but the available information comes from anecdotic reports. In
      this study, we show the clinical and anatomopathological data of a patient
      infected with dengue, who subsequently died of acute multi-organic failure
      related to Staphylococcus aureus infection. The autopsy revealed a severe
      disseminated staphylococcal disease and confirmed dengue infection.

PMID- 20810839
TI  - Index cluster study of dengue virus infection in Nicaragua.
AB  - Traditional study designs do not identify acute asymptomatic or pre-symptomatic
      dengue virus (DENV) infections, thus limiting our understanding of immunologic
      and viral factors that modulate infection outcome. In the 2006 and 2007 dengue
      seasons, we conducted a pilot index cluster study in Managua, Nicaragua, in which
      442 persons living within 50 meters of 22 index cases identified through an
      ongoing pediatric cohort study were evaluated for DENV infection. Post-enrollment
      and pre-enrollment DENV infections were confirmed in 12 (2.7%) and 19 (4.3%)
      contacts, respectively. Five (42%) post-enrollment infections were asymptomatic,
      and DENV-2 was identified in 9 (75%) infections. Phylogenetic analysis with full
      length DENV genomic sequence from contacts, index cases, and cohort dengue cases
      indicated focal transmission and infection outside the local area. We demonstrate
      the feasibility of identification of acute asymptomatic and pre-symptomatic cases
      in urban Latin America, the first report of such a study in the Americas, and
      identify age and concomitant immunity to DENV of contacts as a key factor in
      index cluster study design.

PMID- 20810840
TI  - Early diagnosis of Dengue infection using a commercial Dengue Duo rapid test kit
      for the detection of NS1, IGM, and IGG.
AB  - A commercial Dengue Duo rapid test kit was evaluated for early dengue diagnosis
      by detection of dengue virus NS1 antigen and immunoglobulin M (IgM)/IgG
      antibodies. A total of 420 patient serum samples were subjected to real-time
      reverse transcription-polymerase chain reaction (RT-PCR), in-house IgM capture
      enzyme-linked immunosorbent assay (ELISA), hemagglutination inhibition assay, and
      the SD Dengue Duo rapid test. Of the 320 dengue acute and convalescent sera,
      dengue infection was detected by either serology or RT-PCR in 300 samples
      (93.75%), as compared with 289 samples (90.31%) in the combined SD Duo NS1/IgM.
      The NS1 detection rate is inversely proportional, whereas the IgM detection rate
      is directly proportional to the presence of IgG antibodies. The sensitivity and
      specificity in diagnosing acute dengue infection in the SD Duo NS1/IgM were
      88.65% and 98.75%, respectively. The assay is sensitive and highly specific.
      Detection of both NS1 and IgM by SD Duo gave comparable detection rate by either
      serology or RT-PCR.

PMID- 20810841
TI  - Relationship between nonstructural protein 1 detection and plasma virus load in
      Dengue patients.
AB  - We report data from a prospective observational study performed in Martinique
      during a co-epidemic of dengue virus serotype 2 (DENV-2) and serotype 4 (DENV-4).
      Among 70 serum samples from patients with DENV-2 (n = 21) or DENV-4 (n = 49)
      infections, 47 (67.1%) were positive for dengue nonstructural protein 1 (NS1).
      Antigenemia correlated with plasma virus load and was independent of immune
      status and the time of sampling. Increased viremia 4-6 days after onset of
      illness was associated with NS1 positivity, secondary infection, and severe
      disease. Testing for NS1 could help identify the potentially most severely ill
      patients during the critical phase of dengue.

PMID- 20810843
TI  - Genetic analysis of influenza A/H1N1 of swine origin virus (SOIV) circulating in
      Central and South America.
AB  - Since the first detection of swine origin virus (SOIV) on March 28, 2009, the
      virus has spread worldwide and oseltamivir-resistant strains have already been
      identified in the past months. Here, we show the phylogenetic analysis of 63 SOIV
      isolates from eight countries in Central and South America, and their sensitivity
      to oseltamivir.

PMID- 20810842
TI  - Quantitative analysis of replication and tropisms of Dengue virus type 2 in Aedes
      albopictus.
AB  - Dengue virus serotype 2 (DENV-2) RNA replication profiles and tropisms were
      studied by using quantitative RT-PCR (q-RTPCR) in intrathoracically infected
      Aedes albopictus. The virus RNA replication profiles were diverse in mosquito
      organs. In fat body, brain, salivary gland, and malpighian tubes, it peaked at 8,
      23, 23, and 27 days post-infection, respectively, and then, all declined. In
      midgut, it increased all the time and had no trend of decline. In ovary, it had
      no apparent increase. Subsequent Western blotting of DENV-2 E protein had similar
      results. Using ribosomal protein 7 (rpS7) as an internal control, we found that,
      in salivary gland, brain, fat body, and midgut, the average DENV-2 RNA levels
      (DENV-2 RNA/rpS7 mRNA) were 1,028, 464, 5.6, and 6.2, respectively; in malpighian
      tubes, it was 1, and in ovary, it was far less than 1. These results suggest that
      infection profiles and tropism of DENV-2 RNA in Ae. albopictus organs are
      significantly different.

PMID- 20810844
TI  - High prevalence of HBsAg during pregnancy in Asian communities at Cayenne
      Hospital, French Guiana.
AB  - We described hepatitis B surface antigen (HBsAg) prevalence among 2,347 pregnant
      women having delivered at the Cayenne hospital in 2007 according to ethnicity.
      With 11.0% HBsAg prevalence, Asian women (Hmong and Chinese) were the group with
      the highest risk of hepatitis B virus (HBV) perinatal transmission compared with
      other ethnic groups.

PMID- 20810845
TI  - Guaroa virus infection among humans in Bolivia and Peru.
AB  - Guaroa virus (GROV) was first isolated from humans in Colombia in 1959.
      Subsequent isolates of the virus have been recovered from febrile patients and
      mosquitoes in Brazil, Colombia, and Panama; however, association of the virus
      with human disease has been unclear. As part of a study on the etiology of
      febrile illnesses in Peru and Bolivia, 14 GROV strains were isolated from
      patients with febrile illnesses, and 3 additional cases were confirmed by IgM
      seroconversion. The prevalence rate of GROV antibodies among Iquitos residents
      was 13%; the highest rates were among persons with occupations such as
      woodcutters, fisherman, and oil-field workers. Genetic characterization of
      representative GROV isolates indicated that strains from Peru and Bolivia form a
      monophyletic group that can be distinguished from strains isolated earlier in
      Brazil and Colombia. This study confirms GROV as a cause of febrile illness in
      tropical regions of Central and South America.

PMID- 20810846
TI  - Bayesian spatiotemporal analysis of socio-ecologic drivers of Ross River virus
      transmission in Queensland, Australia.
AB  - This study aims to examine the impact of socio-ecologic factors on the
      transmission of Ross River virus (RRV) infection and to identify areas prone to
      social and ecologic-driven epidemics in Queensland, Australia. We used a Bayesian
      spatiotemporal conditional autoregressive model to quantify the relationship
      between monthly variation of RRV incidence and socio-ecologic factors and to
      determine spatiotemporal patterns. Our results show that the average increase in
      monthly RRV incidence was 2.4% (95% credible interval (CrI): 0.1-4.5%) and 2.0%
      (95% CrI: 1.6-2.3%) for a 1 degrees C increase in monthly average maximum
      temperature and a 10 mm increase in monthly average rainfall, respectively. A
      significant spatiotemporal variation and interactive effect between temperature
      and rainfall on RRV incidence were found. No association between Socio-economic
      Index for Areas (SEIFA) and RRV was observed. The transmission of RRV in
      Queensland, Australia appeared to be primarily driven by ecologic variables
      rather than social factors.

PMID- 20810848
TI  - Quantitative assessment of mitral regurgitation: comparison between three
      dimensional transesophageal echocardiography and magnetic resonance imaging.
AB  - BACKGROUND: quantification of mitral regurgitation severity with 2-dimensional
      (2D) imaging techniques remains challenging. The present study compared the
      accuracy of 2D transesophageal echocardiography (TEE) and 3-dimensional (3D) TEE
      for quantification of mitral regurgitation, using MRI as the reference method.
      METHODS AND RESULTS: two-dimensional and 3D TEE and cardiac MRI were performed in
      30 patients with mitral regurgitation. Mitral effective regurgitant orifice area
      (EROA) and regurgitant volume (Rvol) were estimated with 2D and 3D TEE. With 3D
      TEE, EROA was calculated using planimetry of the color Doppler flow from en face
      views and Rvol was derived by multiplying the EROA by the velocity time integral
      of the regurgitant jet. Finally, using MRI, mitral Rvol was quantified by
      subtracting the aortic flow volume from left ventricular stroke volume. Compared
      with 3D TEE, 2D TEE underestimated the EROA by a mean of 0.13 cm(2). In addition,
      2D TEE underestimated the Rvol by 21.6% when compared with 3D TEE and by 21.3%
      when compared with MRI. In contrast, 3D TEE underestimated the Rvol by only 1.2%
      when compared with MRI. Finally, one third of the patients in grade 1 and >=50%
      of the patients in grade 2 and 3, as assessed with 2D TEE, would have been
      upgraded to a more severe grade, based on the 3D TEE and MRI measurements.
      CONCLUSIONS: quantification of mitral EROA and Rvol with 3D TEE is feasible and
      accurate as compared with MRI and results in less underestimation of the Rvol as
      compared with 2D TEE.

PMID- 20810849
TI  - The socioeconomic impact of musculoskeletal infections.

PMID- 20810850
TI  - Development and use of a second-year musculoskeletal organ-system curriculum: a
      forty-year experience.

PMID- 20810851
TI  - Commentary on an article by Martha M. Murray, MD, et al.: "The effect of skeletal
      maturity on functional healing of the anterior cruciate ligament".

PMID- 20810853
TI  - Radiation therapy for heterotopic ossification prophylaxis acutely after elbow
      trauma: a prospective randomized study.
AB  - BACKGROUND: Heterotopic ossification around the elbow can result in pain, loss of
      motion, and impaired function. We hypothesized that a single dose of radiation
      therapy could be administered safely and acutely after elbow trauma, could
      decrease the number of elbows that would require surgical excision of heterotopic
      ossification, and might improve clinical results. METHODS: A prospective
      randomized study was conducted at three medical centers. Patients with an intra
      articular distal humeral fracture or a fracture-dislocation of the elbow with
      proximal radial and/or ulnar fractures were enrolled. Patients were randomized to
      receive either single-fraction radiation therapy of 700 cGy immediately
      postoperatively (within seventy-two hours) or nothing (the control group).
      Clinical and radiographic assessment was performed at six weeks, three months,
      and six months postoperatively. All adverse events and complications were
      documented prospectively. RESULTS: This study was terminated prior to completion
      because of an unacceptably high number of adverse events reported in the
      treatment group. Data were available on forty-five of the forty-eight patients
      enrolled in this study. When the rate of complications was investigated, a
      significant difference was detected in the frequency of nonunion between the
      groups. Of the nine patients who had a nonunion, eight were in the treatment
      group. The nonunion rate was 38% (eight) of twenty-one patients in the treatment
      group, which was significantly different from the rate of 4% (one) of twenty-four
      patients in the control group (p = 0.007). There were no significant differences
      between the groups with regard to the prevalence of heterotopic ossification,
      postoperative range of motion, or Mayo Elbow Performance Score noted at the time
      of study termination. CONCLUSIONS: This study demonstrated that postoperative
      single-fraction radiation therapy, when used acutely after elbow trauma for
      prophylaxis against heterotopic ossification, may play a role in increasing the
      rate of nonunion at the site of the fracture or an olecranon osteotomy. The
      clinical efficacy of radiation therapy could not be determined on the basis of
      the sample size. Further research is needed to determine the role of limited
      field radiation for prophylaxis against heterotopic ossification after elbow
      trauma.

PMID- 20810854
TI  - The effect of skeletal maturity on functional healing of the anterior cruciate
      ligament.
AB  - BACKGROUND: The effects of skeletal maturity on functional ligament healing are
      unknown. Prior studies have suggested that ligament injuries in skeletally mature
      animals heal with improved mechanical properties. In this study, we hypothesized
      that skeletally immature animals have improved functional healing compared with
      skeletally mature animals. METHODS: Twenty-one Yucatan minipigs (eight juvenile,
      eight adolescent, and five adult animals) underwent bilateral anterior cruciate
      ligament transection. On one side, the ligament injury was left untreated to
      determine the intrinsic healing response as a function of age. On the
      contralateral side, an enhanced suture repair incorporating a collagen-platelet
      composite was performed. Biomechanical properties of the repairs were measured
      after fifteen weeks of healing, and histologic analysis was performed. RESULTS:
      Anterior cruciate ligaments from skeletally immature animals had significantly
      improved structural properties over those of adult animals at three months after
      transection in both the untreated and repair groups. Use of the enhanced suture
      technique provided the most improvement in the adolescent group, in which an
      increase of 85% in maximum load was noted with repair. The repair tissue in the
      adult tissue had the highest degree of hypercellularity at the fifteen-week time
      point. CONCLUSIONS: Functional ligament healing depends on the level of skeletal
      maturity of the animal, with immature animals having a more productive healing
      response than mature animals.

PMID- 20810855
TI  - Stabilizing mechanism in bone-grafting of a large glenoid defect.
AB  - BACKGROUND: Conventional wisdom suggests that the glenoid defect after a shoulder
      dislocation is anteroinferior. However, recent studies have found that the defect
      is located anteriorly. The purposes of this study were (1) to clarify the
      critical size of the anterior defect and (2) to demonstrate the stabilizing
      mechanism of bone-grafting. METHODS: Thirteen cadaver shoulders were
      investigated. With use of a custom testing machine with a 50-N compression force,
      the peak translational force that was needed to move the humeral head and lateral
      humeral displacement were measured. The force was used to evaluate the joint
      stability. An osseous defect was created stepwise in 2-mm increments of the
      defect width. The bone graft was harvested from the coracoid process. The defect
      size was expressed as the estimated defect size divided by the measured glenoid
      length. Testing was performed with (1) the glenoid intact, (2) a simulated
      Bankart lesion, (3) the Bankart lesion repaired, (4) a 2-mm defect, (5) the
      Bankart lesion repaired, (6) the defect bone-grafted, (7) a 4-mm defect, (8) the
      Bankart lesion repaired, (9) the defect bone-grafted, (10) a 6-mm defect, (11)
      the Bankart lesion repaired, (12) the defect bone-grafted, (13) an 8-mm defect,
      (14) the Bankart lesion repaired, and (15) the defect bone-grafted. RESULTS:
      Force and displacement decreased as the size of the osseous defect increased. The
      mean force after the formation of a defect of > or =6 mm (19% of the glenoid
      length) with the Bankart lesion repaired (22 +/- 7 N) was significantly decreased
      compared with the baseline force (52 +/- 11 N). Both the mean force (and standard
      deviation) and displacement returned to the levels of the intact condition (68 +/
      3 N and 2.6 +/- 0.4 mm, respectively) after bone-grafting (72 +/- 12 N and 2.7
      +/- 0.3 mm, respectively). CONCLUSIONS: An osseous defect with a width that is >
      or =19% of the glenoid length remains unstable even after Bankart lesion repair.
      The stabilizing mechanism of bone-grafting was the restoration of the glenoid
      concavity.

PMID- 20810856
TI  - Relationship between the pivot shift and Lachman tests: a cadaver study.
AB  - BACKGROUND: While the Lachman and pivot shift tests have been used clinically for
      decades to assess the anterior cruciate ligament, the relationship between the
      two has undergone limited experimental study. The goal of this study was to
      evaluate biomechanical relationships between the Lachman and pivot shift tests in
      anterior cruciate ligament-deficient and reconstructed knees. METHODS: Knee
      kinematics during simulated pivot-shift testing and anteroposterior knee laxities
      were measured in seventeen knees in the intact condition, in the anterior
      cruciate ligament-deficient condition, and after anterior cruciate ligament
      reconstruction. Pivot shift magnitude was plotted against laxity for all knees
      with the grafts unfixed (the cruciate ligament-deficient condition). The grafts
      were then tensioned to match the laxities of the intact knees, and the change in
      pivot shift magnitude was plotted versus the change in laxity for all knees. In a
      separate series of tests for individual specimens, pivot shift magnitude was
      plotted versus laxity for each knee by incrementally loosening the anterior
      cruciate ligament graft. RESULTS: Linear correlations between pivot shift
      magnitude and absolute laxity for anterior cruciate ligament-deficient knees were
      weak. When the unfixed grafts were tensioned to match anteroposterior laxities of
      the intact knees, changes in pivot shift were better correlated with
      corresponding changes in anteroposterior laxity (r(2) = 0.53 for tibial rotation
      and 0.73 for lateral tibial plateau displacement). When graft fixation was
      progressively loosened for each reconstructed knee, pivot shift magnitude
      increased linearly from the laxity of the intact knee up to an end point of the
      linear range, at which point the slope decreased abruptly. Between this end point
      and the anterior cruciate ligament-deficient condition, further increases in
      pivot shift were relatively small. CONCLUSIONS: Our findings suggest that the
      magnitude of laxity of an injured knee, when considered alone, may not accurately
      predict the magnitude of the pivot shift, but the difference in laxity between
      the injured knee and the normal knee (the injured-normal difference) could be a
      good clinical predictor of the injured-normal difference in the pivot shift. We
      demonstrated that an insufficiently tensioned anterior cruciate ligament graft
      could substantially reduce anterior laxity, while leaving the pivot shift
      evaluation virtually unchanged.

PMID- 20810857
TI  - Computer-assisted and robot-assisted technologies to improve bone-cutting
      accuracy when integrated with a freehand process using an oscillating saw.
AB  - BACKGROUND: In orthopaedic surgery, many interventions involve freehand bone
      cutting with an oscillating saw. Such freehand procedures can produce large
      cutting errors due to the complex hand-controlled positioning of the surgical
      tool. This study was performed to investigate the potential improvements in
      cutting accuracy when computer-assisted and robot-assisted technologies are
      applied to a freehand bone-cutting process when no jigs are available. METHODS:
      We designed an experiment based on a geometrical model of the cutting process
      with use of a simulated bone of rectangular geometry. The target planes were
      defined by three variables: a cut height (t) and two orientation angles (beta and
      gamma). A series of 156 cuts were performed by six operators employing three
      technologically different procedures: freehand, navigated freehand, and robot
      assisted cutting. After cutting, we measured the error in the height t, the
      absolute error in the angles beta and gamma, the flatness, and the location of
      the cut plane with respect to the target plane. RESULTS: The location of the cut
      plane averaged 2.8 mm after use of the navigated freehand process compared with
      5.2 mm after use of the freehand process (p < 0.0001). Further improvements were
      obtained with use of the robot-assisted process, which provided an average
      location of 1.7 mm (p < 0.0001). CONCLUSIONS: Significant improvements in cutting
      accuracy can be achieved when a navigation system or an industrial robot is
      integrated into a freehand bone-cutting process when no jigs are available. The
      procedure for navigated hand-controlled positioning of the oscillating saw
      appears to be easy to learn and use.

PMID- 20810858
TI  - Analysis of osteonecrosis following Pemberton acetabuloplasty in developmental
      dysplasia of the hip: long-term results.
AB  - BACKGROUND: The favorable results of Pemberton acetabuloplasty in children with
      developmental dysplasia of the hip have been well reported. We reviewed our long
      term results related to osteonecrosis of the femoral head after this surgery,
      especially with regard to the effect of excessive inferior displacement of the
      femoral head. METHODS: From 1993 to 1997, we performed 167 Pemberton
      acetabuloplasties in patients with developmental dysplasia of the hip who were
      eighteen months of age or older. Patients who had had prior treatment or
      developmental dysplasia of the hip due to neuromuscular disease were excluded. We
      selected patients who had unilateral developmental dysplasia of the hip, had
      undergone simultaneous open reduction and Pemberton acetabuloplasty between the
      ages of eighteen and thirty-six months, and had been followed for a minimum of
      ten years. Forty-nine patients met these criteria. The patients were divided into
      osteonecrosis-absent and osteonecrosis-present groups according to the criteria
      described by Kalamchi and MacEwen. Preoperative, interim follow-up and final
      radiographs were available for evaluation, as were the results of clinical
      examination. We used the femoral head inferior displacement percentage, measured
      on the radiographs, to quantify the amount of excessive correction
      postoperatively. Outcomes were measured with use of the McKay criteria and the
      Severin criteria. RESULTS: The mean age at the time of surgery was 20.8 months,
      and the mean duration of follow-up was 134.6 months. Twenty-four patients (49%)
      were classified as not having osteonecrosis (the osteonecrosis-absent group) and
      twenty-five patients (51%), as having osteonecrosis (the osteonecrosis-present
      group). There were no significant differences between the two groups in terms of
      sex, age, laterality, Tonnis grade, or preoperative acetabular index. Seven of
      the cases of osteonecrosis were type I, thirteen were type II, one was type III,
      and four were type IV. The inferior displacement percentage revealed significant
      differences between the two groups (p < 0.0001). In the osteonecrosis-absent
      group, 96% of the patients had a radiographically satisfactory result (Severin
      class I or II); however, only 76% of the patients in the osteonecrosis-present
      group had a radiographically satisfactory result (p < 0.0001). According to the
      McKay criteria, there were significant clinical differences between the groups (p
      < 0.0001). CONCLUSIONS: Our results showed significant correlation between
      excessive reduction of the femoral head and the development of osteonecrosis. In
      light of the high prevalence of type-II osteonecrosis, we postulated that the
      lateral epiphyseal branch of the medial circumflex artery was vulnerable to
      compression with increased inferior displacement of the femoral head. The latest
      radiographic and functional results corresponded to the severity of the
      osteonecrosis.

PMID- 20810859
TI  - Perioperative stroke after total joint arthroplasty: prevalence, predictors, and
      outcome.
AB  - BACKGROUND: The risk of perioperative stroke following cardiac and carotid artery
      surgery is well documented. There is an apparent lack of recognition and
      appreciation of this complication after total joint arthroplasty. The present
      study was designed to determine the prevalence of, and outcome after,
      perioperative stroke following total joint arthroplasty. In addition, risk
      factors for the development of this complication were evaluated in an attempt to
      identify a strategy that could minimize the prevalence of this complication.
      METHODS: We performed an observational study of 18,745 consecutive patients
      undergoing primary or revision total hip or total knee arthroplasty from 2000 to
      2007 at our institution. The institutional perioperative stroke rate was 0.2%
      (thirty-six of 18,745). The thirty-six patients who had a stroke included
      seventeen men and nineteen women with a mean age of 68.2 years (range, forty-five
      to eighty-seven years). The average duration of follow-up for all patients and
      controls in the present study was sixty-two months (range, zero to 124.9 months).
      In a predictive model, different patient-related and surgery-related factors that
      could predispose patients to this complication and/or affect outcome were
      evaluated. RESULTS: The first-year mortality among stroke patients was 25% (nine
      of thirty-six), and four of these nine patients died in the hospital following
      total joint arthroplasty. Of three patients who received emergency intra-arterial
      thrombolysis, two had complete neurologic recovery and one died in the hospital.
      The final regression model showed that a history of noncoronary heart disease,
      urgent (versus elective) surgery, general (versus regional) anesthesia, and an
      intraoperative arrhythmia or other alterations in the heart rate during surgery
      are significant predictors of perioperative stroke. CONCLUSIONS: Perioperative
      stroke is a rare but potentially devastating complication of total joint
      arthroplasty, with a high rate of morbidity and mortality. Vigilant attention to
      prevent, detect, and treat this complication in a timely manner may alter the
      course of the disease.

PMID- 20810861
TI  - Total talar replacement following collapse of the talar body as a complication of
      total ankle arthroplasty: a case report.

PMID- 20810860
TI  - Inflammatory blood laboratory levels as markers of prosthetic joint infection: a
      systematic review and meta-analysis.
AB  - BACKGROUND: The preoperative diagnosis of prosthetic joint infection in patients
      with a total hip or knee arthroplasty may rely in part on the use of systemic
      inflammation markers. These markers have unclear accuracy. The objective of this
      review was to summarize the evidence on the accuracy of the peripheral white
      blood-cell count, the erythrocyte sedimentation rate, serum C-reactive protein
      levels, and serum interleukin-6 levels for the diagnosis of prosthetic joint
      infection. METHODS: We searched electronic databases (MEDLINE, EMBASE, Cochrane
      Library, Web of Science, and Scopus) from 1950 through 2009. Eligible studies
      evaluated the accuracy of white blood-cell count, erythrocyte sedimentation rate,
      serum C-reactive protein level, and serum interleukin-6 level for the
      intraoperative diagnosis of prosthetic joint infection at the time of revision
      arthroplasty. Two reviewers working independently extracted study characteristics
      and data to estimate the diagnostic odds ratio and 95% confidence interval for
      each result. RESULTS: We included thirty eligible studies that included 3909
      revision total hip or knee arthroplasties. The prevalence of prosthetic joint
      infection was 32.5% (1270 of 3909). The accuracy of assessed inflammation
      markers, represented with a diagnostic odds ratio, was 314.7 (95% confidence
      interval, 113.0 to 876.8) for interleukin-6 (three studies), 13.1 (95% confidence
      interval, 7.9 to 21.7) for C-reactive protein level (twenty-three studies), 7.2
      (95% confidence interval, 4.7 to 10.9) for erythrocyte sedimentation rate (twenty
      five studies), and 4.4 (95% confidence interval, 2.9 to 6.6) for white blood-cell
      count (fifteen studies). CONCLUSIONS: The diagnostic accuracy for prosthetic
      joint infection was best for interleukin-6, followed by C-reactive protein level,
      erythrocyte sedimentation rate, and white blood-cell count. Given the limited
      numbers of studies assessing interleukin-6 levels, further investigations
      assessing the accuracy of interleukin-6 for the diagnosis of prosthetic joint
      infection are warranted.

PMID- 20810862
TI  - Upper-extremity deep venous thrombosis associated with proximal humeral
      osteomyelitis in a child: a case report.

PMID- 20810863
TI  - Fatal venous air embolism during shoulder arthroscopy: a case report.

PMID- 20810864
TI  - Distal biceps tendon injuries.
AB  - Distal biceps tendon ruptures present with an initial tearing sensation
      accompanied by acute pain; weakness may follow. The hook test is very reliable
      for diagnosing ruptures, and magnetic resonance imaging can provide information
      about the integrity and any intrasubstance degeneration of the tendon. There are
      subtle differences between the outcomes of single and modified two-incision
      operative repairs. With regard to complications, there is a higher prevalence of
      nerve injuries in association with single-incision techniques and a higher
      prevalence of heterotopic ossification in association with two-incision
      techniques. Fixation techniques include the use of bone tunnels, suture anchors,
      interference screws, and cortical fixation buttons. There is no clinical evidence
      supporting the use of one fixation method over another, although cortical button
      fixation has been shown to provide the highest load tolerance and stiffness.
      Postoperative rehabilitation has become more aggressive as fixation methods have
      improved.

PMID- 20810865
TI  - Exchanging the skin bleb for the test tube.

PMID- 20810866
TI  - Timeliness of treatment is more important than choice of reperfusion therapy.

PMID- 20810867
TI  - Q: Are antibiotics indicated for the treatment of aspiration pneumonia?

PMID- 20810868
TI  - The shrinking woman.

PMID- 20810869
TI  - An ulcerated plaque on the hand.

PMID- 20810870
TI  - Charcot neuroarthropathy: An often overlooked complication of diabetes.
AB  - In patients with long-standing, poorly controlled diabetes and peripheral
      neuropathy, a red, hot, swollen foot without open ulceration should raise the
      suspicion of Charcot neuroarthropathy, an often-overlooked diabetic foot
      complication. The authors discuss key diagnostic features and how to
      differentiate this condition from cellulitis, osteomyelitis, and other
      conditions. They review key elements of the workup and emphasize the importance
      of early diagnosis and prompt treatment to preserve a functioning foot.

PMID- 20810871
TI  - Interferon-gamma-release assays: Better than tuberculin skin testing?
AB  - Although the tuberculin skin test has long been the standard for detecting latent
      tuberculosis infection, it has many limitations. Interferon-gamma-release assays
      are gaining acceptance as an alternative. In this paper we present cases to
      illustrate how these new tests can be used and how to interpret the results.

PMID- 20810872
TI  - Hepatitis C virus: Prevention, screening, and interpretation of assays.
AB  - Patients at risk of hepatitis C virus (HCV) infection should be screened for it
      so that they can be treated and potentially cured, or can at least avoid
      transmitting the disease to others. The authors describe why and how to screen
      for HCV and how to interpret the test results.

PMID- 20810873
TI  - Combined reperfusion strategies in ST-segment elevation MI: Rationale and current
      role.
AB  - Primary percutaneous coronary intervention (PCI) is the preferred reperfusion
      strategy for ST-elevation myocardial infarction (MI), but most patients do not
      arrive at a PCI facility within the recommended 90 minutes of first medical
      contact. If delay is expected, timely thrombolysis is recommended, followed by
      early transfer for PCI. The authors review the rationale behind three combined
      reperfusion strategies-facilitated PCI, pharmacoinvasive therapy, and rescue PCI
      and data on their effectiveness.

PMID- 20810874
TI  - Pedagogy for prisoners: an approach to peer health education for inmates.
AB  - There are public health benefits in prisoner health education, given that inmates
      are predominantly from an underclass that is overrepresented in all categories of
      disease and health disadvantage. The author reviews these health issues and
      proposes Freire's approach to education on prisoner-generated, problematic health
      topics within the context of their lives and cultures. Freirean stages proposed
      include identification and investigation of relevant health topics of concern to
      inmates, thematization, problematization of the issues, and development of
      critical health consciousness, followed by dramatization of problems and
      solutions within culturally appropriate contexts. Examples are presented. Health
      rights and responsibilities are discussed in the context of correctional settings
      and the structural and organizational limits they present for staff and inmates.
      This approach to prisoner health education should result in increased health
      literacy and emancipation, which prisoners can later diffuse within their
      communities of origin.

PMID- 20810876
TI  - On the link between sensorimotor adaptation and sensory recalibration.

PMID- 20810875
TI  - Translational neuroscience approaches to hyperphagia.

PMID- 20810877
TI  - Preservation and modulation of specific left hemisphere regions is vital for
      treated recovery from anomia in stroke.
AB  - The location and extent of brain changes that support recovery in chronic stroke
      is probably related to the structural integrity of the remaining cortex. However,
      little is known about the specifics of this relationship and how it influences
      treatment outcome in chronic stroke. To examine this issue, the current study
      examined frank brain damage and changes in cortical activation as predictors of
      language-treatment outcome in patients with chronic aphasia caused by stroke.
      Twenty-six patients received multiple MRI sessions before and after 30 h of
      aphasia treatment targeting anomia, an impairment in the ability to name common
      objects. Improved naming was associated with increased brain activation in the
      anterior and posterior regions of the left hemisphere, whereas damage to the
      posterior portion of the left middle temporal lobe and the temporal-occipital
      junction had a particularly negative effect on treatment outcome. Specifically,
      patients whose brain damage included regions commonly associated with lexical
      retrieval and phonological processing (e.g., Brodmann's areas 37 and 39) were
      less likely to show treatment-related improvement in correct naming compared with
      cases where the same areas were intact. These findings suggest that brain changes
      associated with improved naming ability in chronic aphasia rely on preservation
      and recruitment of eloquent cortex in the left hemisphere. In general, it seems
      likely that a similar relationship between cortical preservation and recruitment
      may also pertain to recovery from other functional impairments in chronic stroke.

PMID- 20810878
TI  - Long-term potentiation-dependent spine enlargement requires synaptic Ca2+
      permeable AMPA receptors recruited by CaM-kinase I.
AB  - It is well established that long-term potentiation (LTP), a paradigm for learning
      and memory, results in a stable enlargement of potentiated spines associated with
      recruitment of additional GluA1-containing AMPA receptors (AMPARs). Although
      regulation of the actin cytoskeleton is involved, the detailed signaling
      mechanisms responsible for this spine expansion are unclear. Here, we used
      cultured mature hippocampal neurons stimulated with a glycine-induced, synapse
      specific form of chemical LTP (GI-LTP). We report that the stable structural
      plasticity (i.e., spine head enlargement and spine length shortening) that
      accompanies GI-LTP was blocked by inhibitors of NMDA receptors (NMDARs; APV) or
      CaM-kinase kinase (STO-609), the upstream activator of CaM-kinase I (CaMKI), as
      well as by transfection with dominant-negative (dn) CaMKI but not dnCaMKIV.
      Recruitment of GluA1 to the spine surface occurred after GI-LTP and was mimicked
      by transfection with constitutively active CaMKI. Spine enlargement induced by
      transfection of GluA1 was associated with synaptic recruitment of Ca(2+)
      permeable AMPARs (CP-AMPARs) as assessed by an increase in the rectification
      index of miniature EPSCs (mEPSCs) and their sensitivity to IEM-1460, a selective
      antagonist of CP-AMPARs. Furthermore, the increase in spine size and mEPSC
      amplitude resulting from GI-LTP itself was blocked by IEM-1460, demonstrating
      involvement of CP-AMPARs. Downstream signaling effectors of CP-AMPARs, identified
      by suppression of their activation by IEM-1460, included the Rac/PAK/LIM-kinase
      pathway that regulates spine actin dynamics. Together, our results suggest that
      synaptic recruitment of CP-AMPARs via CaMKI may provide a mechanistic link
      between NMDAR activation in LTP and regulation of a signaling pathway that drives
      spine enlargement via actin polymerization.

PMID- 20810879
TI  - Bidirectional connectivity between hemispheres occurs at multiple levels in
      language processing but depends on sex.
AB  - Our aim was to determine the direction of interhemispheric communication in a
      phonological task in regions involved in different levels of processing.
      Effective connectivity analysis was conducted on functional magnetic resonance
      imaging data from 39 children (ages 9-15 years) performing rhyming judgment on
      spoken words. The results show interaction between hemispheres at multiple
      levels. First, there is unidirectional transfer of information from right to left
      at the sensory level of primary auditory cortex. Second, bidirectional
      connections between superior temporal gyri (STGs) suggest a reciprocal
      cooperation between hemispheres at the level of phonological and prosodic
      processing. Third, a direct connection from right STG to left inferior frontal
      gyrus suggest that information processed in the right STG is integrated into the
      final stages of phonological segmentation required for the rhyming decision.
      Intrahemispheric connectivity from primary auditory cortex to STG was stronger in
      the left compared to the right hemisphere. These results support a model of
      cooperation between hemispheres, with asymmetric interhemispheric and
      intrahemispheric connectivity consistent with the left hemisphere specialization
      for phonological processing. Finally, we found greater interhemispheric
      connectivity in girls compared to boys, consistent with the hypothesis of a more
      bilateral representation of language in females than males. However,
      interhemispheric communication was associated with slow performance and low
      verbal intelligent quotient within girls. We suggest that females may have the
      potential for greater interhemispheric cooperation, which may be an advantage in
      certain tasks. However, in other tasks too much communication between hemispheres
      may interfere with task performance.

PMID- 20810880
TI  - Experience-dependent development of coordinated hippocampal spatial activity
      representing the similarity of related locations.
AB  - To learn we must identify and remember experiences uniquely but also generalize
      across experiences to extract common features. Hippocampal place cells can show
      similar firing patterns across locations, but the functional significance of this
      repetitive activity and the role of experience and learning in generating it are
      not understood. We therefore examined rat hippocampal place cell activity in the
      context of spatial tasks with multiple similar spatial trajectories. We found
      that, in environments with repeating elements, about half of the recorded place
      cells showed path-equivalent firing, where individual neurons are active in
      multiple similar locations. In contrast, place cells from animals performing a
      similar task in an environment with fewer similar elements were less likely to
      fire in a path-equivalent manner. Moreover, in the environment with multiple
      repeating elements, path equivalence developed with experience in the task, and
      increased path equivalence was associated with increased moment-by-moment
      correlations between pairs of path-equivalent neurons. As a result, correlated
      firing among path-equivalent neurons increased with experience. These findings
      suggest that coordinated hippocampal ensembles can encode generalizations across
      locations. Thus, path-equivalent ensembles are well suited to encode similarities
      among repeating elements, providing a framework for associating specific
      behaviors with multiple locations, while neurons without this repetitive
      structure maintain a distinct population code.

PMID- 20810881
TI  - The spinal substrate of the suppression of action during action observation.
AB  - We have previously demonstrated that the forelimb representations of the primary
      motor and somatosensory cortices, as well as several premotor and parietal areas,
      are activated by both action-execution and action-observation, indicating that
      the spectator mentally simulates the observed action. Moreover, several studies
      demonstrated repeatedly that corticospinal excitability is modulated during
      action observation, providing evidence of an activation of the observer's motor
      system. However, evidence for the involvement of the spinal cord in action
      observation is controversial. The aim of the present study was to explore whether
      and how action-observation affects the spinal cord. To this end, we analyzed the
      spinal cord of eight monkeys (Macaca mulatta) trained to either execute reaching
      to-grasp movements or observe the experimenter performing the same movements.
      Observation of grasping induced a bilateral decrease of glucose consumption in
      the spinal forelimb representation, whereas execution of grasping induced an
      increase of glucose utilization in the same area, ipsilaterally to the grasping
      hand. The depression of overall activity in the cervical enlargement of the
      spinal cord for action-observation may explain the suppression of overt
      movements, despite the activation of the observer's motor system.

PMID- 20810883
TI  - Distinct presynaptic and postsynaptic dismantling processes of Drosophila
      neuromuscular junctions during metamorphosis.
AB  - Synapse remodeling is a widespread and fundamental process that underlies the
      formation of neuronal circuitry during development and in adaptation to
      physiological and/or environmental changes. However, the mechanisms of synapse
      remodeling are poorly understood. Synapses at the neuromuscular junction (NMJ) in
      Drosophila larvae undergo dramatic and extensive remodeling during metamorphosis
      to generate adult-specific synapses. To explore the molecular and cellular
      processes of synapse elimination, we performed confocal microscopy, live imaging,
      and electron microscopy (EM) of NMJ synapses during the early stages of
      metamorphosis in Drosophila in which the expressions of selected genes were
      genetically altered. We report that the localization of the postsynaptic scaffold
      protein Disc large (Dlg) becomes diffuse first and then undetectable, as larval
      muscles undergo histolysis, whereas presynaptic vesicles aggregate and are
      retrogradely transported along axons in synchrony with the formation of filopodia
      like structures along NMJ elaborations and retraction of the presynaptic plasma
      membrane. EM revealed that the postsynaptic subsynaptic reticulum vacuolizes in
      the early stages of synapse dismantling concomitant with diffuse localization of
      Dlg. Ecdysone is the major hormone that drives metamorphosis. Blockade of the
      ecdysone signaling specifically in presynaptic neurons by expression of a
      dominant-negative form of ecdysone receptors delayed presynaptic but not
      postsynaptic dismantling. However, inhibition of ecdysone signaling, as well as
      ubiquitination pathway or apoptosis specifically in postsynaptic muscles,
      arrested both presynaptic and postsynaptic dismantling. These results demonstrate
      that presynaptic and postsynaptic dismantling takes place through different
      mechanisms and that the postsynaptic side plays an instructive role in synapse
      dismantling.

PMID- 20810882
TI  - Internally generated error signals in monkey frontal eye field during an inferred
      motion task.
AB  - An internal model for predictive saccades in frontal cortex was investigated by
      recording neurons in monkey frontal eye field (FEF) during an inferred motion
      task. Monkeys were trained to make saccades to the extrapolated position of a
      small moving target that was rendered temporarily invisible and whose trajectory
      was altered. On approximately two-thirds of the trials, monkeys made multiple
      saccades while the target was invisible. Primary saccades were correlated with
      extrapolated target position. Secondary saccades significantly reduced residual
      errors resulting from imperfect accuracy of the first saccade. These observations
      suggest that the second saccade was corrective. Because there was no visual
      feedback, corrective saccades could only be driven by an internally generated
      error signal. Neuronal activity in the frontal eye field was directionally tuned
      before both primary and secondary saccades. Separate subpopulations of cells
      encoded either saccade direction or direction error before the second saccade.
      These results suggest that FEF neurons encode the error after the first saccade,
      as well as the direction of the second saccade. Hence, FEF appears to contribute
      to detecting and correcting movement errors based on internally generated
      signals.

PMID- 20810884
TI  - Generalization lags behind learning on an auditory perceptual task.
AB  - The generalization of learning from trained to untrained conditions is of great
      potential value because it markedly increases the efficacy of practice. In
      principle, generalization and the learning itself could arise from either the
      same or distinct neural changes. Here, we assessed these two possibilities in the
      realm of human perceptual learning by comparing the time course of improvement on
      a trained condition (learning) to that on an untrained condition (generalization)
      for an auditory temporal-interval discrimination task. While significant
      improvement on the trained condition occurred within 2 d, generalization to the
      untrained condition lagged behind, only emerging after 4 d. The different time
      courses for learning and generalization suggest that these two types of
      perceptual improvement can arise from at least partially distinct neural changes.
      The notably longer time course for generalization than learning demonstrates that
      increasing the duration of training can be an effective means to increase the
      number of conditions to which learning generalizes on perceptual tasks.

PMID- 20810885
TI  - Rapid sequences of population activity patterns dynamically encode task-critical
      spatial information in parietal cortex.
AB  - We characterized the temporal dynamics of population activity in parietal cortex
      of monkeys as they solved a spatial cognitive problem posed by an object
      construction task. We applied pattern classification techniques to characterize
      patterns of activity coding object-centered side, a task-defined variable
      specifying whether an object component was located on the left or right side of a
      reference object, regardless of its retinocentric position. During a period in
      which the value of object-centered side, as defined by task events, remained
      constant, parietal cortex represented this variable using a dynamic neural code
      by activating neurons with the same spatial preference in rapid succession so
      that the pattern of active neurons changed dramatically while the spatial
      information they collectively encoded remained stable. Furthermore, if the
      neurons shared the same spatial preference, then their pretrial activity
      (measured before objects were shown) was correlated to a degree that scaled as a
      positive linear function of how close together in time the neurons would be
      activated later in the trial. Finally, we found that while parietal cortex
      represented task-critical spatial information using a dynamic neural code, it
      simultaneously represented task-irrelevant spatial information using a stationary
      neural code. These data demonstrate that dynamic spatial representations exist in
      parietal cortex, provide novel insight into the synaptic mechanisms that generate
      them, and suggest they may preferentially encode task-critical spatial
      information.

PMID- 20810886
TI  - Rab11 and its effector Rab coupling protein contribute to the trafficking of beta
      1 integrins during axon growth in adult dorsal root ganglion neurons and PC12
      cells.
AB  - Integrins play an important part in axon growth, but integrin traffic in neurons
      is poorly understood. Expression of the tenascin-C-binding integrin alpha9
      promotes axon regeneration. We have therefore studied the mechanism by which
      alpha9 integrin and its partner beta1 are trafficked along axons and at the
      growth cone using adult DRG neurons and PC12 cells. We have focused on the small
      GTPase Rab11 and its effector Rab coupling protein (RCP), as they are involved in
      the long-range trafficking of beta1 integrins in other cells. Rab11 colocalizes
      with alpha9 and other alpha integrins and with beta1 integrin in growth cones and
      axons, and immunopurified Rab11 vesicles contain alpha9 and beta1. Endocytosed
      beta1 integrins traffic via Rab11. However, Rab11 vesicles in axons are generally
      static, and alpha9 integrins undergo bouts of movement during which they leave
      the Rab11 compartment. In growth cones, alpha9 and beta1 overlap with RCP,
      particularly at the growth cone periphery. We show that beta1 integrin
      trafficking during neurite outgrowth involves Rab11 and RCP, and that
      manipulation of these molecules alters surface integrin levels and axon growth,
      and can be used to enhance alpha9 integrin-dependent neurite outgrowth. Our data
      suggest that manipulation of trafficking via Rab11 and RCP could be a useful
      strategy for promoting integrin-dependent axonal regeneration.

PMID- 20810887
TI  - Dynamic properties of human brain structure: learning-related changes in cortical
      areas and associated fiber connections.
AB  - Recent findings in neuroscience suggest that adult brain structure changes in
      response to environmental alterations and skill learning. Whereas much is known
      about structural changes after intensive practice for several months, little is
      known about the effects of single practice sessions on macroscopic brain
      structure and about progressive (dynamic) morphological alterations relative to
      improved task proficiency during learning for several weeks. Using T1-weighted
      and diffusion tensor imaging in humans, we demonstrate significant gray matter
      volume increases in frontal and parietal brain areas following only two sessions
      of practice in a complex whole-body balancing task. Gray matter volume increase
      in the prefrontal cortex correlated positively with subject's performance
      improvements during a 6 week learning period. Furthermore, we found that
      microstructural changes of fractional anisotropy in corresponding white matter
      regions followed the same temporal dynamic in relation to task performance. The
      results make clear how marginal alterations in our ever changing environment
      affect adult brain structure and elucidate the interrelated reorganization in
      cortical areas and associated fiber connections in correlation with improvements
      in task performance.

PMID- 20810888
TI  - Prostaglandin E2-induced synaptic plasticity in neocortical networks of
      organotypic slice cultures.
AB  - Traumatic brain injury (TBI) is a major cause of epilepsy, yet the mechanisms
      underlying the progression from TBI to epilepsy are unknown. TBI induces the
      expression of COX-2 (cyclooxygenase-2) and increases levels of prostaglandin E2
      (PGE2). Here, we demonstrate that acutely applied PGE2 (2 mum) decreases
      neocortical network activity by postsynaptically reducing excitatory synaptic
      transmission in acute and organotypic neocortical slices of mice. In contrast,
      long-term exposure to PGE2 (2 mum; 48 h) presynaptically increases excitatory
      synaptic transmission, leading to a hyperexcitable network state that is
      characterized by the generation of paroxysmal depolarization shifts (PDSs). PDSs
      were also evoked as a result of depriving organotypic slices of activity by
      treating them with tetrodotoxin (TTX, 1 mum; 48 h). This treatment predominantly
      increased postsynaptically excitatory synaptic transmission. The network and
      cellular effects of PGE2 and TTX treatments reversed within 1 week. Differences
      in the underlying mechanisms (presynaptic vs postsynaptic) as well as occlusion
      experiments in which slices were exposed to TTX plus PGE2 suggest that the two
      substances evoke distinct forms of homeostatic plasticity, both of which result
      in a hyperexcitable network state. PGE2 and TTX (alone or together with PGE2)
      also increased levels of apoptotic cell death in organotypic slices. Thus, we
      hypothesize that the increase in excitability and apoptosis may constitute the
      first steps in a cascade of events that eventually lead to epileptogenesis
      triggered by TBI.

PMID- 20810889
TI  - Establishing the boundaries: the hippocampal contribution to imagining scenes.
AB  - When we visualize scenes, either from our own past or invented, we impose a
      viewpoint for our "mind's eye" and we experience the resulting image as spatially
      coherent from that viewpoint. The hippocampus has been implicated in this
      process, but its precise contribution is unknown. We tested a specific hypothesis
      based on the spatial firing properties of neurons in the hippocampal formation of
      rats, that this region supports the construction of spatially coherent mental
      images by representing the locations of the environmental boundaries surrounding
      our viewpoint. Using functional magnetic resonance imaging, we show that
      hippocampal activation increases parametrically with the number of enclosing
      boundaries in the imagined scene. In contrast, hippocampal activity is not
      modulated by a nonspatial manipulation of scene complexity nor to increasing
      difficulty of imagining the scenes in general. Our findings identify a specific
      computational role for the hippocampus in mental imagery and episodic
      recollection.

PMID- 20810890
TI  - Population coding of interaural time differences in gerbils and barn owls.
AB  - Interaural time differences (ITDs) are the primary cue for the localization of
      low-frequency sound sources in the azimuthal plane. For decades, it was assumed
      that the coding of ITDs in the mammalian brain was similar to that in the avian
      brain, where information is sparsely distributed across individual neurons, but
      recent studies have suggested otherwise. In this study, we characterized the
      representation of ITDs in adult male and female gerbils. First, we performed
      behavioral experiments to determine the acuity with which gerbils can use ITDs to
      localize sounds. Next, we used different decoders to infer ITDs from the activity
      of a population of neurons in central nucleus of the inferior colliculus. These
      results show that ITDs are not represented in a distributed manner, but rather in
      the summed activity of the entire population. To contrast these results with
      those from a population where the representation of ITDs is known to be sparsely
      distributed, we performed the same analysis on activity from the external nucleus
      of the inferior colliculus of adult male and female barn owls. Together, our
      results support the idea that, unlike the avian brain, the mammalian brain
      represents ITDs in the overall activity of a homogenous population of neurons
      within each hemisphere.

PMID- 20810891
TI  - Rapid delivery of internalized signaling receptors to the somatodendritic surface
      by sequence-specific local insertion.
AB  - The recycling pathway is a major route for delivering signaling receptors to the
      somatodendritic plasma membrane. We investigated the cell biological basis for
      the remarkable selectivity and speed of this process. We focused on the mu-opioid
      neuropeptide receptor and the beta(2)-adrenergic catecholamine receptor, two
      seven-transmembrane signaling receptors that traverse the recycling pathway
      efficiently after ligand-induced endocytosis and localize at steady state
      throughout the postsynaptic surface. Rapid recycling of each receptor in
      dissociated neuronal cultures was mediated by a receptor-specific cytoplasmic
      sorting sequence. Total internal reflection fluorescence microscopy imaging
      revealed that both sequences drive recycling via discrete vesicular fusion events
      in the cell body and dendritic shaft. Both sequences promoted recycling via
      "transient"-type events characterized by nearly immediate lateral spread of
      receptors after vesicular insertion resembling receptor insertion events observed
      previously in non-neural cells. The sequences differed in their abilities to
      produce distinct "persistent"-type events at which inserted receptors lingered
      for a variable time period before lateral spread. Both types of insertion event
      generated a uniform distribution of receptors in the somatodendritic plasma
      membrane when imaged over a 1 min interval, but persistent events uniquely
      generated a punctate surface distribution over a 10 s interval. These results
      establish sequence-directed recycling of signaling receptors in CNS neurons and
      show that this mechanism has the ability to generate receptor-specific patterns
      of local surface distribution on a timescale overlapping that of rapid
      physiological signaling.

PMID- 20810892
TI  - Human posterior parietal cortex plans where to reach and what to avoid.
AB  - In this time-resolved functional magnetic resonance imaging (fMRI) study, we
      aimed to trace the neuronal correlates of covert planning processes that precede
      visually guided motor behavior. Specifically, we asked whether human posterior
      parietal cortex has prospective planning activity that can be distinguished from
      activity related to retrospective visual memory and attention. Although various
      electrophysiological studies in monkeys have demonstrated such motor planning at
      the level of parietal neurons, comparatively little support is provided by recent
      human imaging experiments. Rather, a majority of experiments highlights a role of
      human posterior parietal cortex in visual working memory and attention. We thus
      sought to establish a clear separation of visual memory and attention from
      processes related to the planning of goal-directed motor behaviors. To this end,
      we compared delayed-response tasks with identical mnemonic and attentional
      demands but varying degrees of motor planning. Subjects memorized multiple target
      locations, and in a random subset of trials targets additionally instructed (1)
      desired goals or (2) undesired goals for upcoming finger reaches. Compared with
      the memory/attention-only conditions, both latter situations led to a specific
      increase of preparatory fMRI activity in posterior parietal and dorsal premotor
      cortex. Thus, posterior parietal cortex has prospective plans for upcoming
      behaviors while considering both types of targets relevant for action: those to
      be acquired and those to be avoided.

PMID- 20810893
TI  - Coupled activity-dependent trafficking of synaptic SK2 channels and AMPA
      receptors.
AB  - Small conductance Ca(2+)-activated K(+) type 2 (SK2) channels are expressed in
      the postsynaptic density of CA1 neurons where they are activated by synaptically
      evoked Ca(2+) influx to limit the size of EPSPs and spine Ca(2+) transients. At
      Schaffer collateral synapses, the induction of long-term potentiation (LTP)
      increases the alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor
      (AMPAR)-mediated contribution to synaptic transmission and decreases the synaptic
      SK2 channel contribution through protein kinase A-dependent channel endocytosis.
      Using a combination of electrophysiology and immunoelectron microscopy in mice,
      the relationship between the dynamics of spine SK2 channels and AMPARs was
      investigated. Unlike AMPARs, synaptic SK2 channels under basal conditions do not
      rapidly recycle. Furthermore, SK2 channels occupy a distinct population of
      endosomes separate from AMPARs. However, blocking vesicular exocytosis or the
      delivery of synaptic GluA1-containing AMPARs during the induction of LTP blocks
      SK2 channel endocytosis. By approximately 2 h after the induction of LTP,
      synaptic SK2 channel expression and function are restored. Thus, LTP-dependent
      endocytosis of SK2 is coupled to LTP-dependent AMPA exocytosis, and the
      approximately 2 h window after the induction of LTP during which synaptic SK2
      activity is absent may be important for consolidating the later phases of LTP.

PMID- 20810894
TI  - Cocaine-induced chromatin remodeling increases brain-derived neurotrophic factor
      transcription in the rat medial prefrontal cortex, which alters the reinforcing
      efficacy of cocaine.
AB  - Cocaine self-administration alters patterns of gene expression in the brain that
      may underlie cocaine-induced neuronal plasticity. In the present study, male
      Sprague Dawley rats were allowed to self-administer cocaine (0.25 mg/infusion) 2
      h/d for 14 d, followed by 7 d of forced abstinence. Compared with yoked saline
      control rats, cocaine self-administration resulted in increased brain-derived
      neurotrophic factor (BDNF) protein levels in the rat medial prefrontal cortex
      (mPFC). To examine the functional relevance of this finding, cocaine self
      administration maintained under a progressive ratio schedule of reinforcement was
      assessed after short hairpin RNA-induced suppression of BDNF expression in the
      mPFC. Decreased BDNF expression in the mPFC increased the cocaine self
      administration breakpoint. Next, the effect of cocaine self-administration on
      specific BDNF exons was assessed; results revealed selectively increased BDNF
      exon IV-containing transcripts in the mPFC. Moreover, there were significant
      cocaine-induced increases in acetylated histone H3 (AcH3) and phospho-cAMP
      response element binding protein (pCREB) association with BDNF promoter IV. In
      contrast, there was decreased methyl-CpG-binding protein 2 (MeCP2) association
      with BDNF promoter IV in the mPFC of rats that previously self-administered
      cocaine. Together, these results indicate that cocaine-induced increases in BDNF
      promoter IV transcript in the mPFC are driven by increased binding of AcH3 and
      pCREB as well as decreased MeCP2 binding at this BDNF promoter. Collectively,
      these results indicate that cocaine self-administration remodels chromatin in the
      mPFC, resulting in increased expression of BDNF, which appears to represent a
      compensatory neuroadaptation that reduces the reinforcing efficacy of cocaine.

PMID- 20810896
TI  - The medial preoptic nucleus integrates the central influences of testosterone on
      the paraventricular nucleus of the hypothalamus and its extended circuitries.
AB  - Testosterone contributes to sex differences in hypothalamic-pituitary-adrenal
      (HPA) function in humans and rodents, but the central organization of this
      regulation remains unclear. The medial preoptic nucleus (MPN) stands out as an
      important candidate in this regard because it contains androgen receptors and
      projects to forebrain nuclei integrating cognitive-affective information and
      regulating HPA responses to homeostatic threat. These include the HPA effector
      neurons of the paraventricular nucleus (PVN) of the hypothalamus, medial
      amygdala, and lateral septum. To test the extent to which androgen receptors in
      the MPN engage these cell groups, we compared in adult male rats the effects of
      unilateral microimplants of testosterone and the androgen receptor antagonist
      hydroxyflutamide into the MPN on acute restraint induced activation and/or
      neuropeptide expression levels. The basic effects of these implants were
      lateralized to the sides of the nuclei ipsilateral to the implants. Testosterone,
      but not hydroxyflutamide implants, decreased stress-induced Fos and arginine
      vasopressin (AVP) heteronuclear RNA expression in the PVN, as well as Fos
      expression in the lateral septum. In unstressed animals, AVP mRNA expression in
      the PVN decreased and increased in response to testosterone and hydroxflutamide
      MPN implants, respectively. The differential influences of these implants on AVP
      mRNA expression were opposite in the medial amygdala. These results confirm a
      role for androgen receptors in the MPN to concurrently modulate neuropeptide
      expression and activational responses in the PVN and its extended circuitries.
      This suggests that the MPN is capable of bridging converging limbic influences to
      the HPA axis with changes in gonadal status.

PMID- 20810895
TI  - Progressive NKCC1-dependent neuronal chloride accumulation during neonatal
      seizures.
AB  - Seizures induce excitatory shifts in the reversal potential for GABA(A)-receptor
      mediated responses, which may contribute to the intractability of electro
      encephalographic seizures and preclude the efficacy of widely used GABAergic
      anticonvulsants such as phenobarbital. We now report that, in intact hippocampi
      prepared from neonatal rats and transgenic mice expressing Clomeleon, recurrent
      seizures progressively increase the intracellular chloride concentration ([Cl(
      )](i)) assayed by Clomeleon imaging and invert the net effect of GABA(A) receptor
      activation from inhibition to excitation assayed by the frequency of action
      potentials and intracellular Ca(2+) transients. These changes correlate with
      increasing frequency of seizure-like events and reduction in phenobarbital
      efficacy. The Na(+)-K(+)-2Cl(-) (NKCC1) cotransporter blocker bumetanide
      inhibited seizure-induced neuronal Cl(-) accumulation and the consequent
      facilitation of recurrent seizures. Our results demonstrate a novel mechanism by
      which seizure activity leads to [Cl(-)](i) accumulation, thereby increasing the
      probability of subsequent seizures. This provides a potential mechanism for the
      early crescendo phase of neonatal seizures.

PMID- 20810898
TI  - Chemical coding for cardiovascular sympathetic preganglionic neurons in rats.
AB  - Cocaine and amphetamine-regulated transcript peptide (CART) is present in a
      subset of sympathetic preganglionic neurons in the rat. We examined the
      distribution of CART-immunoreactive terminals in rat stellate and superior
      cervical ganglia and adrenal gland and found that they surround neuropeptide Y
      immunoreactive postganglionic neurons and noradrenergic chromaffin cells. The
      targets of CART-immunoreactive preganglionic neurons in the stellate and superior
      cervical ganglia were shown to be vasoconstrictor neurons supplying muscle and
      skin and cardiac-projecting postganglionic neurons: they did not target non
      vasoconstrictor neurons innervating salivary glands, piloerector muscle, brown
      fat, or adrenergic chromaffin cells. Transneuronal tracing using pseudorabies
      virus demonstrated that many, but not all, preganglionic neurons in the
      vasoconstrictor pathway to forelimb skeletal muscle were CART immunoreactive.
      Similarly, analysis with the confocal microscope confirmed that 70% of boutons in
      contact with vasoconstrictor ganglion cells contained CART, whereas 30% did not.
      Finally, we show that CART-immunoreactive cells represented 69% of the
      preganglionic neuron population expressing c-Fos after systemic hypoxia. We
      conclude that CART is present in most, although not all, cardiovascular
      preganglionic neurons but not thoracic preganglionic neurons with non
      cardiovascular targets. We suggest that CART immunoreactivity may identify the
      postulated "accessory" preganglionic neurons, whose actions may amplify vasomotor
      ganglionic transmission.

PMID- 20810897
TI  - GABA(B) receptor modulation of serotonin neurons in the dorsal raphe nucleus and
      escalation of aggression in mice.
AB  - The serotonin (5-HT) system in the brain has been studied more than any other
      neurotransmitter for its role in the neurobiological basis of aggression.
      However, which mechanisms modulate the 5-HT system to promote escalated
      aggression is not clear. We here explore the role of GABAergic modulation in the
      raphe nuclei, from which most 5-HT in the forebrain originates, on escalated
      aggression in male mice. Pharmacological activation of GABA(B), but not GABA(A),
      receptors in the dorsal raphe nucleus (DRN) escalated aggressive behaviors. In
      contrast, GABA agonists did not escalate aggressive behaviors after
      microinjection into the median raphe nucleus. The aggression-heightening effect
      of the GABA(B) agonist baclofen depended on the activation of 5-HT neurons in the
      DRN because it was blocked by coadministration of the 5-HT(1A) agonist 8-OH-DPAT
      [((+/-)-8-hydroxy-2-(di-n-propylamino)tetralin) hydrobromide] (DPAT), which acts
      on autoreceptors and inhibits 5-HT neural activity. In vivo microdialysis showed
      that GABA(B) activation in the DRN increased extracellular 5-HT level in the
      medial prefrontal cortex. This may be attributable to an indirect action via
      presynaptic GABA(B) receptors. The presynaptic GABA(B) receptors suppress Ca(2+)
      channel activity and inhibit neurotransmission, and the coadministration of N
      type Ca(2+) channel blocker facilitated the effect of baclofen. These findings
      suggest that the indirect disinhibition of 5-HT neuron activity by presynaptic
      GABA(B) receptors on non-5-HT neurons in the DRN is one of the neurobiological
      mechanisms of escalated aggression.

PMID- 20810899
TI  - Specific sites within the ligand-binding domain and ion channel linkers modulate
      NMDA receptor gating.
AB  - Gating in the NMDA receptor is initiated in the extracellular ligand-binding
      domain (LBD) and is ultimately propagated via three linkers-S1-M1, M3-S2, and S2
      M4-to the ion channel. M3-S2 directly couples LBD movements into channel gating,
      but the functional and structural contributions of S1-M1 and S2-M4 to the overall
      gating process are unknown. A scan of substituted cysteines in and around the
      NMDA receptor S1-M1 and S2-M4 with a bulky cysteine-reactive reagent identified
      numerous positions that showed potentiation of glutamate-activated as well as
      leak currents. As indexed by MK801 (dizocilpine hydrogen maleate), an open
      channel blocker, this potentiation was attributable to an increase in open
      probability, an interpretation confirmed for a subset of positions with single
      channel recordings. The magnitude of this gating effect, acting through S1-M1 or
      S2-M4, was dependent on the intrinsic gating properties of the NMDA receptors,
      being more effective in the inherently low open probability GluN2C- than the
      higher open probability GluN2A-subunit-containing receptors. For the majority of
      these potentiation positions, we propose that alteration of gating arises from
      steric destabilization of contact interfaces where close apposition of the
      contacting partners is necessary for efficient channel closure. Our results
      therefore indicate that the NMDA receptor S1-M1 and S2-M4 linkers are dynamic
      during gating and can modulate the overall energetics of this process.
      Furthermore, the results conceptualize a mechanistic, as well as a possible
      structural, framework for pharmacologically targeting the linkers through
      noncompetitive and subunit-specific modes of action.

PMID- 20810900
TI  - Parkin directly modulates 26S proteasome activity.
AB  - Parkinson's disease (PD) is a common neurodegenerative disease that involves the
      deterioration of dopaminergic neurons in the substantia nigra pars compacta.
      Although the etiology of PD remains poorly understood, recent genetic,
      postmortem, and experimental evidence shows that abnormal protein accumulation
      and subsequent aggregate formation are prominent features of both sporadic and
      familial PD. While proteasome dysfunction is observed in PD, diverse mutations in
      the parkin gene are linked to early-onset autosomal-recessive forms of familial
      PD. We demonstrate that parkin, an E3 ubiquitin ligase, activates the 26S
      proteasome in an E3 ligase activity-independent manner. Furthermore, an N
      terminal ubiquitin-like domain within parkin is critical for the activation of
      the 26S proteasome through enhancing the interaction between 19S proteasomal
      subunits, whereas the PD-linked R42P mutant abolishes this action. The current
      findings point to a novel role for parkin for 26S proteasome assembly and suggest
      that parkin mutations contribute to the proteasomal dysfunction in PD.

PMID- 20810901
TI  - Agrp neurons mediate Sirt1's action on the melanocortin system and energy
      balance: roles for Sirt1 in neuronal firing and synaptic plasticity.
AB  - Sirt1 has been associated with various effects of calorie restriction, including
      an increase in lifespan. Here we show in mice that a central regulatory component
      in energy metabolism, the hypothalamic melanocortin system, is affected by Sirt1,
      which promotes the activity and connectivity of this system resulting in negative
      energy balance. In adult mice, the pharmacological inhibition of brain Sirt1
      activity decreased Agrp neuronal activity and the inhibitory tone on the
      anorexigenic POMC neurons, as measured by the number of synaptic inputs to these
      neurons. When a Sirt1 inhibitor (EX-527) was injected either peripherally (i.p.,
      10 mg/kg) or directly into the brain (i.c.v., 1.5 nmol/mouse), it decreased both
      food intake during the dark cycle and ghrelin-induced food intake. This effect on
      feeding is mediated by upstream melanocortin receptors, because the MC4R
      antagonist, SHU9119, reversed Sirt1's effect on food intake. This action of Sirt1
      required an appropriate shift in the mitochondrial redox state: in the absence of
      such an adaptation enabled by the mitochondrial protein, UCP2, Sirt1-induced
      cellular and behavioral responses were impaired. In accordance with the
      pharmacological results, the selective knock-out of Sirt1 in hypothalamic Agrp
      neurons through the use of Cre-Lox technology decreased electric responses of
      Agrp neurons to ghrelin and decreased food intake, leading to decreased lean
      mass, fat mass, and body weight. The present data indicate that Sirt1 has a
      central mode of action by acting on the NPY/Agrp neurons to affect body
      metabolism.

PMID- 20810902
TI  - Associative plasticity at excitatory synapses facilitates recruitment of fast
      spiking interneurons in the dentate gyrus.
AB  - Fast-spiking perisomatic-inhibitory interneurons (PIIs) receive convergent
      excitation and mediate both feedforward and feedback inhibition in cortical
      microcircuits. However, it remains poorly understood how convergent excitatory
      inputs recruit PIIs to produce precisely timed inhibition. Here, we analyzed the
      interaction of inputs from the entorhinal cortex [perforant path (PP)] and from
      local granule cells [mossy fibers (MFs)] onto PIIs in the rat dentate gyrus (DG).
      PP stimulation alone activates PIIs with low temporal precision. Interestingly,
      when PP and MFs are coactivated with a 10 ms delay, PIIs discharge with precise
      timing. Moreover, repeated coactivation of the two inputs induces associative
      long-term potentiation (LTP) at MF synapses. Under these conditions, a single
      potentiated MF input is sufficient to recruit PIIs in a reliable and highly
      precise manner to provide feedback inhibition. MF-LTP depends on the discharge of
      PIIs, indicating Hebbian plasticity. However, MF-LTP is preserved when NMDA
      receptors are blocked but depends on transmission through Ca(2+)-permeable AMPA
      receptors (AMPARs). PP-PII synapses, in contrast, lack Ca(2+)-permeable AMPARs
      and do not show plasticity on associative activation. Thus, precise recruitment
      of PIIs requires excitation through MF-PII synapses during feedforward
      activation. We propose that associative plasticity at these synapses is a central
      mechanism that adjusts inhibition levels to maintain sparse activity and to
      improve signal-to-noise ratio in the DG network.

PMID- 20810904
TI  - Norepinephrine promotes microglia to uptake and degrade amyloid beta peptide
      through upregulation of mouse formyl peptide receptor 2 and induction of insulin
      degrading enzyme.
AB  - Locus ceruleus (LC) is the main subcortical site of norepinephrine synthesis. In
      Alzheimer's disease (AD) patients and rodent models, degeneration of LC neurons
      and reduced levels of norepinephrine in LC projection areas are significantly
      correlated with the increase in amyloid plaques, neurofibrillary tangles, and
      severity of dementia. Activated microglia play a pivotal role in the progression
      of AD by either clearing amyloid beta peptide (Abeta) deposits through uptake of
      Abeta or releasing cytotoxic substances and proinflammatory cytokines. Here, we
      investigated the effect of norepinephrine on Abeta uptake and clearance by murine
      microglia and explored the underlying mechanisms. We found that murine microglia
      cell line N9 and primary microglia expressed beta(2) adrenergic receptor (AR) but
      not beta(1) and beta(3)AR. Norepinephrine and isoproterenol upregulated the
      expression of Abeta receptor mFPR2, a mouse homolog of human formyl peptide
      receptor FPR2, through activation of beta(2)AR in microglia. Norepinephrine also
      induced mFPR2 expression in mouse brain. Activation of beta(2)AR in microglia
      promoted Abeta(42) uptake through upregulation of mFPR2 and enhanced spontaneous
      cell migration but had no effect on cell migration in response to mFPR2 agonists.
      Furthermore, activation of beta(2)AR on microglia induced the expression of
      insulin-degrading enzyme and increased the degradation of Abeta(42). Mechanistic
      studies showed that isoproterenol induced mFPR2 expression through ERK1/2-NF
      kappaB and p38-NF-kappaB signaling pathways. These findings suggest that
      noradrenergic innervation from LC is needed to maintain adequate Abeta uptake and
      clearance by microglia, and norepinephrine is a link between neuron and microglia
      to orchestrate the host response to Abeta in AD.

PMID- 20810903
TI  - The role of calcium/calmodulin-activated calcineurin in rapid and slow
      endocytosis at central synapses.
AB  - Although the calcium/calmodulin-activated phosphatase calcineurin may
      dephosphorylate many endocytic proteins, it is not considered a key molecule in
      mediating the major forms of endocytosis at synapses-slow, clathrin-dependent and
      the rapid, clathrin-independent endocytosis. Here we studied the role of
      calcineurin in endocytosis by reducing calcium influx, inhibiting calmodulin with
      pharmacological blockers and knockdown of calmodulin, and by inhibiting
      calcineurin with pharmacological blockers and knock-out of calcineurin. These
      manipulations significantly inhibited both rapid and slow endocytosis at the
      large calyx-type synapse in 7- to 10-d-old rats and mice, and slow, clathrin
      dependent endocytosis at the conventional cultured hippocampal synapse of rats
      and mice. These results suggest that calcium influx during nerve firing activates
      calcium/calmodulin-dependent calcineurin, which controls the speed of both rapid
      and slow endocytosis at synapses by dephosphorylating endocytic proteins. The
      calcium/calmodulin/calcineurin signaling pathway may underlie regulation of
      endocytosis by nerve activity and calcium as reported at many synapses over the
      last several decades.

PMID- 20810905
TI  - P/Q and N channels control baseline and spike-triggered calcium levels in
      neocortical axons and synaptic boutons.
AB  - Cortical axons contain a diverse range of voltage-activated ion channels,
      including Ca(2+) currents. Interestingly, Ca(2+) channels are not only located at
      presynaptic terminals, but also in the axon initial segment (AIS), suggesting a
      potentially important role in the regulation of action potential generation and
      neuronal excitability. Here, using two-photon microscopy and whole-cell patch
      clamp recording, we examined the properties and role of calcium channels located
      in the AIS and presynaptic terminals of ferret layer 5 prefrontal cortical
      pyramidal cells in vitro. Subthreshold depolarization of the soma resulted in an
      increase in baseline and spike-triggered calcium concentration in both the AIS
      and nearby synaptic terminals. The increase in baseline calcium concentration
      rose with depolarization and fell with hyperpolarization with a time constant of
      approximately 1 s and was blocked by removal of Ca(2+) from the bathing medium.
      The increases in calcium concentration at the AIS evoked by subthreshold or
      suprathreshold depolarization of the soma were blocked by the P/Q-channel
      antagonist omega-agatoxin IVA or the N-channel antagonist omega-conotoxin GVIA or
      both. The presence of these channels in the AIS pyramidal cells was confirmed
      with immunochemistry. Block of these channels slowed axonal action potential
      repolarization, apparently from reduction of the activation of a Ca(2+)-activated
      K(+) current, and increased neuronal excitability. These results demonstrate
      novel mechanisms by which calcium currents may control the electrophysiological
      properties of axonal spike generation and neurotransmitter release in the
      neocortex.

PMID- 20810906
TI  - Perisynaptic glia discriminate patterns of motor nerve activity and influence
      plasticity at the neuromuscular junction.
AB  - In the nervous system, the induction of plasticity is coded by patterns of
      synaptic activity. Glial cells are now recognized as dynamic partners in a wide
      variety of brain functions, including the induction and modulation of various
      forms of synaptic plasticity. However, it appears that glial cells are usually
      activated by stereotyped, sustained neuronal activity, and little attention has
      been given to more subtle changes in the patterns of synaptic activation. To this
      end, we used the mouse neuromuscular junction as a simple and useful model to
      study glial modulation of synaptic plasticity. We used two patterns of motor
      nerve stimulation that mimic endogenous motor-neuronal activity. A continuous
      stimulation induced a post-tetanic potentiation and a phasic Ca(2+) response in
      perisynaptic Schwann cells (PSCs), glial cells at this synapse. A bursting
      pattern of activity induced a post-tetanic depression and oscillatory Ca(2+)
      responses in PSCs. The different Ca(2+) responses in PSCs indicate that they
      decode the pattern of synaptic activity. Furthermore, the chelation of glial
      Ca(2+) impaired the production of the sustained plasticity events indicating that
      PSCs govern the outcome of synaptic plasticity. The mechanisms involved were
      studied using direct photo-activation of PSCs with caged Ca(2+) that mimicked
      endogenous plasticity. Using specific pharmacology and transgenic knock-out
      animals for adenosine receptors, we showed that the sustained depression was
      mediated by A1 receptors while the sustained potentiation is mediated by A(2A)
      receptors. These results demonstrate that glial cells decode the pattern of
      synaptic activity and subsequently provide bidirectional feedback to synapses.

PMID- 20810908
TI  - Calcium-activated force of human muscle fibers following a standardized eccentric
      contraction.
AB  - Peak Ca(2+)-activated specific force (force/fiber cross-sectional area) of human
      chemically skinned vastus lateralis muscle fiber segments was determined before
      and after a fixed-end contraction or an eccentric contraction of standardized
      magnitude (+0.25 optimal fiber length) and velocity (0.50 unloaded shortening
      velocity). Fiber myosin heavy chain (MHC) isoform content was assayed by SDS
      PAGE. Posteccentric force deficit, a marker of damage, was similar for type I and
      IIa fibers but threefold greater for type IIa/IIx hybrid fibers. A fixed-end
      contraction had no significant effect on force. Multiple linear regression
      revealed that posteccentric force was explained by a model consisting of a fiber
      type-independent and a fiber type-specific component (r(2) = 0.91). Preeccentric
      specific force was directly associated with a greater posteccentric force
      deficit. When preeccentric force was held constant, type I and IIa fibers showed
      identical susceptibility to damage, while type IIa/IIx fibers showed a
      significantly greater force loss. This heightened sensitivity to damage was
      directly related to the amount of type IIx MHC in the hybrid fiber. Our model
      reveals a fiber-type sensitivity of the myofilament lattice or cytoskeleton to
      mechanical strain that can be described as follows: type IIa/IIx > type IIa =
      type I. If these properties extend to fibers in vivo, then alterations in the
      number of type IIa/IIx fibers may modify a muscle's susceptibility to eccentric
      damage.

PMID- 20810907
TI  - A role for AMPK in increased insulin action after serum starvation.
AB  - Serum starvation is a common cell culture procedure for increasing cellular
      response to insulin, though the mechanism for the serum starvation effect is not
      understood. We hypothesized that factors known to potentiate insulin action
      [e.g., AMP-activated protein kinase (AMPK) and p38] or to be involved in insulin
      signaling leading to glucose transport [e.g., Akt, PKCzeta, AS160, and ataxia
      telangiectasia mutated (ATM)] would be phosphorylated during serum starvation and
      would be responsible for increased insulin action after serum starvation. L6
      myotubes were incubated in serum-containing or serum-free medium for 3 h. Levels
      of phosphorylated AMPK, Akt, and ATM were greater in serum-starved cells than in
      control cells. Serum starvation did not affect p38, PKCzeta, or AS160
      phosphorylation or insulin-stimulated Akt or AS160 phosphorylation. Insulin had
      no effect on glucose transport in control cells but caused an increase in glucose
      uptake for serum-starved cells that was preventable by compound C (an AMPK
      inhibitor), by expression of dominant negative AMPK (AMPK-DN), and by KU55933 (an
      ATM inhibitor). ATM protein levels increased during serum starvation, and this
      increase in ATM was prevented by compound C and AMPK-DN. Thus, it appears that
      AMPK is required for the serum starvation-related increase in insulin-stimulated
      glucose transport, with ATM as a possible downstream effector.

PMID- 20810909
TI  - A muscle resident cell population promotes fibrosis in hindlimb skeletal muscles
      of mdx mice through the Wnt canonical pathway.
AB  - Previous work has pointed to a role for the Wnt canonical pathway in fibrosis
      formation in aged skeletal muscles. In the present study, we studied the
      dystrophic mdx mouse, which displays skeletal muscle fibrosis. Our results
      indicated that the muscle resident stromal cell (mrSC) population in the muscles
      of dystrophic mice is higher than in the muscles of age-matched wild-type mice.
      Wnt3a promoted the proliferation of and collagen expression by cultured mrSCs but
      arrested the growth of and collagen expression by cultured myoblasts. Injections
      of Wnt3A in the tibialis anterior muscles of adult wild-type mice significantly
      enhanced the mrSC population and collagen deposition compared with the
      contralateral muscles. Conversely, an injection of the Wnt antagonist Dickkof
      protein (DKK1) into the skeletal muscles of mdx mice significantly reduced
      collagen deposition. These results suggested that the Wnt canonical pathway
      expands the population of mrSCs and stimulates their production of collagen as
      observed during aging and in various myopathies.

PMID- 20810910
TI  - Shank2 redistributes with NaPilla during regulated endocytosis.
AB  - Serum phosphate levels are acutely impacted by the abundance of sodium-phosphate
      cotransporter IIa (NaPiIIa) in the apical membrane of renal proximal tubule
      cells. PSD-95/Disks Large/Zonula Occludens (PDZ) domain-containing proteins bind
      NaPiIIa and likely contribute to the delivery, retention, recovery, and
      trafficking of NaPiIIa. Shank2 is a distinctive PDZ domain protein that binds
      NaPiIIa. Its role in regulating NaPiIIa activity, distribution, and abundance is
      unknown. In the present in vivo study, rats were maintained on a low-phosphate
      diet, and then plasma phosphate levels were acutely elevated by high-phosphate
      feeding to induce the recovery, endocytosis, and degradation of NaPiIIa. Western
      blot analysis of renal cortical tissue from rats given high-phosphate feed showed
      NaPiIIa and Shank2 underwent degradation. Quantitative immunofluorescence
      analyses, including microvillar versus intracellular intensity ratios and
      intensity correlation quotients, showed that Shank2 redistributed with NaPiIIa
      during the time course of NaPiIIa endocytosis. Furthermore, NaPiIIa and Shank2
      trafficked through distinct endosomal compartments (clathrin, early endosomes,
      lysosomes) with the same temporal pattern. These in vivo findings indicate that
      Shank2 is positioned to coordinate the regulated endocytic retrieval and
      downregulation of NaPiIIa in rat renal proximal tubule cells.

PMID- 20810911
TI  - PECAM-1 regulates proangiogenic properties of endothelial cells through
      modulation of cell-cell and cell-matrix interactions.
AB  - Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is a member of the
      immunoglobulin superfamily of cell adhesion molecules with important roles in
      angiogenesis and inflammation. However, the molecular and cellular mechanisms,
      and the role that specific PECAM-1 isoforms play in these processes, remain
      elusive. We recently showed attenuation of retinal vascular development and
      neovascularization in PECAM-1-deficient (PECAM-1-/-) mice. To gain further
      insight into the role of PECAM-1 in these processes, we isolated primary retinal
      endothelial cells (EC) from wild-type (PECAM-1+/+) and PECAM-1-/- mice. Lack of
      PECAM-1 had a significant impact on endothelial cell-cell and cell-matrix
      interactions, resulting in attenuation of cell migration and capillary
      morphogenesis. Mechanistically these changes were associated with a significant
      decrease in expression of endothelial nitric oxide synthase (eNOS) and nitric
      oxide (NO) bioavailability in PECAM-1-/- retinal EC. PECAM-1-/- retinal EC also
      exhibited a lower rate of apoptosis under basal and challenged conditions,
      consistent with their increased growth rate. Furthermore, reexpression of PECAM-1
      was sufficient to restore migration and capillary morphogenesis of null cells in
      an isoform-specific manner. Thus PECAM-1 expression modulates proangiogenic
      properties of EC, and these activities are significantly influenced by
      alternative splicing of its cytoplasmic domain.

PMID- 20810912
TI  - Hypoxia downregulates p53 but induces apoptosis and enhances expression of BAD in
      cultures of human syncytiotrophoblasts.
AB  - Hypoxia is commonly assigned a role in the placental dysfunction characteristic
      of preeclampsia and intrauterine growth restriction. We previously showed that
      hypoxia upregulates p53 and enhances apoptosis in primary cultures of human
      cytotrophoblasts. Here we tested the hypothesis that hypoxia also induces
      apoptosis in syncytiotrophoblasts by upregulation of p53. Primary cultures of
      human cytotrophoblasts that had differentiated into syncytiotrophoblasts by 52 h
      were exposed for <=24 h to 20% or <1% oxygen in the presence or absence of
      staurosporine or the p53 modulators nutlin-3, pifithrin-alpha, and pifithrin-MU.
      Proteins were detected by Western blot analysis or immunofluorescence. Compared
      with 20% oxygen, exposure of syncytiotrophoblasts to <1% oxygen upregulated
      hypoxia-inducible factor (HIF)-1alpha and rapidly downregulated p53. Activity of
      p53 in hypoxic syncytiotrophoblasts was reduced by the higher expression of the
      negative p53 regulator MDMX and by the reduction of phosphorylation of p53 at
      Ser(392), which reduces p53 activity. Conversely, staurosporine, a kinase
      inhibitor, and nutlin-3, a drug that enhances p53 expression, both raised p53
      levels and increased the rate of apoptosis in syncytiotrophoblasts compared with
      vehicle controls. Immunofluorescence staining showed p53 immunolocalized to both
      cytoplasm and nuclei of nutlin-3-exposed syncytiotrophoblasts. The hypoxia
      induced apoptosis in syncytiotrophoblasts correlated with enhanced expression of
      the proapoptotic BAD and a reduced level of antiapoptotic BAD phosphorylated on
      Ser(112). We surmise that cell death induced by extreme hypoxia in
      syncytiotrophoblasts follows a non-p53-dependent pathway, unlike that of a
      nonhypoxic stimulus and unlike hypoxic cytotrophoblasts. We speculate that
      downregulation of p53 activity in response to hypoxia reduces or eliminates the
      apoptosis transduced by the p53 pathway in syncytiotrophoblasts, thereby limiting
      cell death and maintaining the integrity of this critical villous component.

PMID- 20810913
TI  - Monocyte CD147 is induced by advanced glycation end products and high glucose
      concentration: possible role in diabetic complications.
AB  - CD147 is a highly glycosylated transmembrane protein that is known to play a role
      in regulation of many protein families. It has the unique ability to maintain
      functional activity in both the membrane bound state and in the soluble form.
      CD147 is known to play a role in regulation of matrix metalloproteinase (MMP)
      expression, but whether its expression is affected by the diabetic milieu is not
      known, and its role in regulation of monocyte MMPs in this environment has not
      been investigated. Therefore, in this study we investigated the effect of
      advanced glycation end products (AGEs) and high glucose (HG; 25 mM), on monocyte
      CD147 expression. Culture of THP-1 monocytes in the presence of AGEs or HG
      significantly increased CD147 at the gene and protein level. THP-1 cell results
      were confirmed using freshly isolated monocytes from human volunteers. The effect
      of AGEs and HG on CD147 expression was also mimicked by addition of
      proinflammatory cytokines. Addition of AGEs or HG also increased expression of
      monocyte MMP-1 and MMP-9 but not MMP-2. This increase in MMPs was significantly
      attenuated by inhibition of CD147 using either a small interfering RNA or an anti
      CD147 antibody. Inhibition of NF-kappaB or addition of antibodies to either TNF
      alpha or the receptor for AGE (RAGE) each significantly prevented in a dose
      dependent manner the induction of CD147 gene and protein by AGE and also
      decreased MMP-1 and MMP-9. This novel result shows that AGEs can induce monocyte
      CD147 expression, an effect mediated by inflammatory pathways and RAGE. Because
      MMPs play a role in monocyte migration, inhibition of their regulator CD147 may
      assist in the prevention of diabetic complications, particularly those where
      monocyte infiltration is an early initiating event.

PMID- 20810914
TI  - S100A1: a physiological modulator of RYR1, Ca2+ release, and contractility in
      skeletal muscle. Focus on "S100A1 promotes action potential-initiated calcium
      release flux and force production in skeletal muscle".

PMID- 20810915
TI  - pH sensitivity of ammonium transport by Rhbg.
AB  - Rhbg is a membrane glycoprotein that is involved in NH(3)/NH(4)(+) transport.
      Several models have been proposed to describe Rhbg, including an electroneutral
      NH(4)(+)/H(+) exchanger, a uniporter, an NH(4)(+) channel, or even a gas channel.
      In this study, we characterized the pH sensitivity of Rhbg expressed in Xenopus
      oocytes. We used two-electrode voltage clamp and ion-selective microelectrodes to
      measure NH(4)(+)-induced [and methyl ammonium (MA(+))] currents and changes in
      intracellular pH (pH(i)), respectively. In oocytes expressing Rhbg, 5 mM NH(4)Cl
      (NH(3)/NH(4)(+)) at extracellular pH (pH(o)) of 7.5 induced an inward current,
      decreased pH(i), and depolarized the cell. Raising pH(o) to 8.2 significantly
      enhanced the NH(4)(+)-induced current and pH(i) changes, whereas decreasing bath
      pH to 6.5 inhibited these changes. Lowering pH(i) (decreased by butyrate) also
      inhibited the NH(4)(+)-induced current and pH(i) decrease. In oocytes expressing
      Rhbg, 5 mM methyl amine hydrochloride (MA/MA(+)), often used as an NH(4)Cl
      substitute, induced an inward current, a pH(i) increase (not a decrease), and
      depolarization of the cell. Exposing the oocyte to MA/MA(+) at alkaline bath pH
      (8.2) enhanced the MA(+)-induced current, whereas lowering bath pH to 6.5
      inhibited the MA(+) current completely. Exposing the oocyte to MA/MA(+) at low
      pH(i) abolished the MA(+)-induced current and depolarization; however, pH(i)
      still increased. These data indicate that 1) transport of NH(4)(+) and MA/MA(+)
      by Rhbg is pH sensitive; 2) electrogenic NH(4)(+) and MA(+) transport are
      stimulated by alkaline pH(o) but inhibited by acidic pH(i) or pH(o); and 3)
      electroneutral transport of MA by Rhbg is likely but is less sensitive to pH
      changes.

PMID- 20810917
TI  - Real-time mapping of electronic structure with single-shot two-dimensional
      electronic spectroscopy.
AB  - Electronic structure and dynamics determine material properties and behavior.
      Important time scales for electronic dynamics range from attoseconds to
      milliseconds. Two-dimensional optical spectroscopy has proven an incisive tool to
      probe fast spatiotemporal electronic dynamics in complex multichromophoric
      systems. However, acquiring these spectra requires long point-by-point
      acquisitions that preclude observations on the millisecond and microsecond time
      scales. Here we demonstrate that imaging temporally encoded information within a
      homogeneous sample allows mapping of the evolution of the electronic Hamiltonian
      with femtosecond temporal resolution in a single-laser-shot, providing real-time
      maps of electronic coupling. This method, which we call GRadient-Assisted Photon
      Echo spectroscopy (GRAPE), eliminates phase errors deleterious to Fourier
      spectroscopies while reducing the acquisition time by orders of magnitude using
      only conventional optical components. In analogy to MRI in which magnetic field
      gradients are used to create spatial correlation maps, GRAPE spectroscopy takes
      advantage of a similar type of spatial encoding to construct electronic
      correlation maps. Unlike magnetic resonance, however, this spatial encoding of
      the nonlinear polarization along the excitation frequency axis of the two
      dimensional spectrum results in no loss in signal while simultaneously reducing
      overall noise. Correlating the energy transfer events and electronic coupling
      occurring in tens of femtoseconds with slow dynamics on the subsecond time scale
      is fundamentally important in photobiology, solar energy research, nonlinear
      spectroscopy, and optoelectronic device characterization.

PMID- 20810916
TI  - Plasma gelsolin modulates cellular response to sphingosine 1-phosphate.
AB  - Hypogelsolinemia is observed in patients with different states of acute or
      chronic inflammation such as sepsis, rheumatoid arthritis, and multiple
      sclerosis. In animal models of sepsis, repletion of plasma gelsolin reduces
      septic mortality. However, the functions of extracellular gelsolin and the
      mechanisms leading to its protective nature are poorly understood. Potential
      mechanisms involve gelsolin's extracellular actin scavenging function or its
      ability to bind bioactive lipids or proinflammatory mediators, which would limit
      inflammatory responses and prevent tissue damage. Here we report that human
      plasma gelsolin binds to sphingosine 1-phosphate (S1P), a pleiotropic cellular
      agonist involved in various immune responses, and to its synthetic structural
      analog FTY720P (Gilenya). The fluorescence intensity of a rhodamine B-labeled
      phosphatidylinositol 4,5-bisphosphate binding peptide derived from gelsolin and
      the optical density of recombinant human plasma gelsolin (rhpGSN) were found to
      decrease after the addition of S1P or FTY720P. Gelsolin's ability to depolymerize
      F-actin also decreased progressively with increasing addition of S1P. Transient
      increases in phosphorylation of extracellular signal-regulated kinase in bovine
      aortic endothelial cells (BAECs) after S1P treatment were inhibited by rhpGSN.
      The ability of S1P to increase F-actin content and the elastic modulus of primary
      astrocytes and BAECs was also prevented by rhpGSN. Evaluation of S1P and gelsolin
      levels in cerebrospinal fluid reveals a low concentration of gelsolin and a high
      concentration of S1P in samples obtained from patients suffering from lymphatic
      meningitis. These findings suggest that gelsolin-mediated regulation of S1P
      bioactivity may be important to maintain immunomodulatory balance at inflammatory
      sites.

PMID- 20810918
TI  - Transformation and crystallization energetics of synthetic and biogenic amorphous
      calcium carbonate.
AB  - Amorphous calcium carbonate (ACC) is a metastable phase often observed during low
      temperature inorganic synthesis and biomineralization. ACC transforms with aging
      or heating into a less hydrated form, and with time crystallizes to calcite or
      aragonite. The energetics of transformation and crystallization of synthetic and
      biogenic (extracted from California purple sea urchin larval spicules,
      Strongylocentrotus purpuratus) ACC were studied using isothermal acid solution
      calorimetry and differential scanning calorimetry. Transformation and
      crystallization of ACC can follow an energetically downhill sequence: more
      metastable hydrated ACC -> less metastable hydrated ACC => anhydrous ACC ~
      biogenic anhydrous ACC => vaterite -> aragonite -> calcite. In a given reaction
      sequence, not all these phases need to occur. The transformations involve a
      series of ordering, dehydration, and crystallization processes, each lowering the
      enthalpy (and free energy) of the system, with crystallization of the dehydrated
      amorphous material lowering the enthalpy the most. ACC is much more metastable
      with respect to calcite than the crystalline polymorphs vaterite or aragonite.
      The anhydrous ACC is less metastable than the hydrated, implying that the
      structural reorganization during dehydration is exothermic and irreversible.
      Dehydrated synthetic and anhydrous biogenic ACC are similar in enthalpy. The
      transformation sequence observed in biomineralization could be mainly
      energetically driven; the first phase deposited is hydrated ACC, which then
      converts to anhydrous ACC, and finally crystallizes to calcite. The initial
      formation of ACC may be a first step in the precipitation of calcite under a wide
      variety of conditions, including geological CO(2) sequestration.

PMID- 20810919
TI  - Correction for hidden confounders in the genetic analysis of gene expression.
AB  - Understanding the genetic underpinnings of disease is important for screening,
      treatment, drug development, and basic biological insight. One way of getting at
      such an understanding is to find out which parts of our DNA, such as single
      nucleotide polymorphisms, affect particular intermediary processes such as gene
      expression. Naively, such associations can be identified using a simple
      statistical test on all paired combinations of genetic variants and gene
      transcripts. However, a wide variety of confounders lie hidden in the data,
      leading to both spurious associations and missed associations if not properly
      addressed. We present a statistical model that jointly corrects for two
      particular kinds of hidden structure--population structure (e.g., race, family
      relatedness), and microarray expression artifacts (e.g., batch effects), when
      these confounders are unknown. Applying our method to both real and synthetic,
      human and mouse data, we demonstrate the need for such a joint correction of
      confounders, and also the disadvantages of other possible approaches based on
      those in the current literature. In particular, we show that our class of models
      has maximum power to detect eQTL on synthetic data, and has the best performance
      on a bronze standard applied to real data. Lastly, our software and the
      associations we found with it are available at http://www.microsoft.com/science.

PMID- 20810920
TI  - In situ growth of a PEG-like polymer from the C terminus of an intein fusion
      protein improves pharmacokinetics and tumor accumulation.
AB  - This paper reports a general in situ method to grow a polymer conjugate solely
      from the C terminus of a recombinant protein. GFP was fused at its C terminus
      with an intein; cleavage of the intein provided a unique thioester moiety at the
      C terminus of GFP that was used to install an atom transfer radical
      polymerization (ATRP) initiator. Subsequent in situ ATRP of oligo(ethylene
      glycol) methyl ether methacrylate (OEGMA) yielded a site-specific (C-terminal)
      and stoichiometric conjugate with high yield and good retention of protein
      activity. A GFP-C-poly(OEGMA) conjugate (hydrodynamic radius (R(h)): 21 nm)
      showed a 15-fold increase in its blood exposure compared to the protein (R(h):
      3.0 nm) after intravenous administration to mice. This conjugate also showed a 50
      fold increase in tumor accumulation, 24 h after intravenous administration to
      tumor-bearing mice, compared to the unmodified protein. This approach for in situ
      C-terminal polymer modification of a recombinant protein is applicable to a large
      subset of recombinant protein and peptide drugs and provides a general
      methodology for improvement of their pharmacological profiles.

PMID- 20810921
TI  - Doing with less sleep remains a dream.

PMID- 20810922
TI  - A genetic mosaic approach for neural circuit mapping in Drosophila.
AB  - Transgenic manipulation of subsets of brain cells is increasingly used for
      studying behaviors and their underlying neural circuits. In Drosophila, the GAL4
      upstream activating sequence (UAS) binary system is powerful for gene
      manipulation, but GAL4 expression is often too broad for fine mapping of neural
      circuits. Here, we describe the development of unique molecular genetic tools to
      restrict GAL4 expression patterns. Building on the GAL4-UAS system, our method
      adds two components: a collection of enhancer-trap recombinase, Flippase (ET
      FLP), transgenic lines that provide inheritable, reproducible, and tissue
      specific FLP and an FRT-dependent GAL80 "flip-in" construct that converts FLP
      expression into tissue-specific repression of GAL4 by GAL80. By including a UAS
      encoded fluorescent protein, circuit morphology can be simultaneously marked
      while the circuit function is assessed using another UAS transgene. In a proof-of
      principle analysis, we applied this ET-FLP-induced intersectional GAL80/GAL4
      repression (FINGR) method to map the neural circuitry underlying fly wing
      inflation. The FINGR system is versatile and powerful in combination with the
      vast collection of GAL4 lines for neural circuit mapping as well as for clonal
      analysis based on the infusion of the yeast-derived FRT/FLP system of mitotic
      recombination into Drosophila. The strategies and tactics underlying our FINGR
      system are also applicable to other genetically amenable organisms in which
      transgenes including the GAL4, UAS, GAL80, and FLP factors can be applied.

PMID- 20810923
TI  - Glucocorticoids in the prefrontal cortex enhance memory consolidation and impair
      working memory by a common neural mechanism.
AB  - It is well established that acute administration of adrenocortical hormones
      enhances the consolidation of memories of emotional experiences and,
      concurrently, impairs working memory. These different glucocorticoid effects on
      these two memory functions have generally been considered to be independently
      regulated processes. Here we report that a glucocorticoid receptor agonist
      administered into the medial prefrontal cortex (mPFC) of male Sprague-Dawley rats
      both enhances memory consolidation and impairs working memory. Both memory
      effects are mediated by activation of a membrane-bound steroid receptor and
      depend on noradrenergic activity within the mPFC to increase levels of cAMP
      dependent protein kinase. These findings provide direct evidence that
      glucocorticoid effects on both memory consolidation and working memory share a
      common neural influence within the mPFC.

PMID- 20810924
TI  - A quantitative model of glucose signaling in yeast reveals an incoherent feed
      forward loop leading to a specific, transient pulse of transcription.
AB  - The ability to design and engineer organisms demands the ability to predict
      kinetic responses of novel regulatory networks built from well-characterized
      biological components. Surprisingly, few validated kinetic models of complex
      regulatory networks have been derived by combining models of the network
      components. A major bottleneck in producing such models is the difficulty of
      measuring in vivo rate constants for components of complex networks. We
      demonstrate that a simple, genetic approach to measuring rate constants in vivo
      produces an accurate kinetic model of the complex network that Saccharomyces
      cerevisiae employs to regulate the expression of genes encoding glucose
      transporters. The model predicts a transient pulse of transcription of HXT4 (but
      not HXT2 or HXT3) in response to addition of a small amount of glucose to cells,
      an outcome we observed experimentally. Our model also provides a mechanistic
      explanation for this result: HXT2-4 are governed by a type 2, incoherent feed
      forward regulatory loop involving the Rgt1 and Mig2 transcriptional repressors.
      The efficiency with which Rgt1 and Mig2 repress expression of each HXT gene
      determines which of them have a pulse of transcription in response to glucose.
      Finally, the model correctly predicts how lesions in the feed forward loop change
      the kinetics of induction of HXT4 expression.

PMID- 20810925
TI  - During EPO or anemia challenge, erythroid progenitor cells transit through a
      selectively expandable proerythroblast pool.
AB  - Investigations of bone marrow (BM) erythroblast development are important for
      clinical concerns but are hindered by progenitor cell and tissue availability. We
      therefore sought to more specifically define dynamics, and key regulators, of the
      formation of developing BM erythroid cell cohorts. A unique Kit(
      )CD71(high)Ter119(-) "stage E2" proerythroblast pool first is described, which
      (unlike its Kit(+) "stage E1" progenitors, or maturing Ter119(+) "stage E3"
      progeny) proved to selectively expand ~ 7-fold on erythropoietin challenge.
      During short-term BM transplantation, stage E2 proerythroblasts additionally
      proved to be a predominantly expanded progenitor pool within spleen. This E1->E2
      >E3 erythroid series reproducibly formed ex vivo, enabling further
      characterizations. Expansion, in part, involved E1 cell hyperproliferation
      together with rapid E2 conversion plus E2 stage restricted BCL2 expression.
      Possible erythropoietin/erythropoietin receptor proerythroblast stage specific
      events were further investigated in mice expressing minimal erythropoietin
      receptor alleles. For a hypomorphic erythropoietin receptor-HM allele, major
      defects in erythroblast development occurred selectively at stage E2. In
      addition, stage E2 cells proved to interact productively with primary BM stromal
      cells in ways that enhanced both survival and late-stage development. Overall,
      findings reveal a novel transitional proerythroblast compartment that deploys
      unique expansion devices.

PMID- 20810926
TI  - Leukemia-initiating cells in human T-lymphoblastic leukemia exhibit
      glucocorticoid resistance.
AB  - T-cell acute lymphoblastic leukemia (T-ALL) is associated with a significant risk
      of disease relapse, but the biological basis for relapse is poorly understood.
      Here, we identify leukemiainitiating cells (L-ICs) on the basis of functional
      assays and prospective isolation and report a role for L-ICs in T-ALL disease and
      relapse. Long-term proliferation in response to NOTCH1 activating signals in OP9
      DL1 coculture system or capacity to initiate leukemia in xenografts by the
      CD7(+)CD1a(-) subset of primary T-ALL samples was superior to other subsets,
      refining the identity of T-ALL L-ICs. T-ALL engraftment was improved in nonobese
      diabetic/severe combined immunodeficiency (NOD/scid)IL2Rgamma(null) (NSG) mice
      compared with NOD/scid with anti-CD122 treatment (NS122), but both showed changes
      in leukemia immunophenotype. Clonal analysis of xenografts using the TCRG locus
      revealed the presence of subclones of T-ALL L-ICs, some of which possess a
      selective growth advantage and correlated with the capacity of CD7(+)CD1a(+)
      xenograft cells to engraft secondary NSG mice. Treatment of high-risk T-ALL
      xenografts eliminated CD1a(+) T-ALL cells, but CD1a(-) cells were resistant and
      their number was increased. Our results establish that primary CD1a(-) T-ALL
      cells are functionally distinct from CD1a(+) cells and that the CD7(+)CD1a(-)
      subset is enriched for L-IC activity that may be involved in mediating disease
      relapse after therapy.

PMID- 20810927
TI  - Pan-histone deacetylase inhibitor panobinostat depletes CXCR4 levels and
      signaling and exerts synergistic antimyeloid activity in combination with CXCR4
      antagonists.
AB  - Stromal cell derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 are
      involved in the directional homing to the bone marrow niches and in peripheral
      mobilization of normal and transformed hematopoietic stem and myeloid progenitor
      cells. Elevated CXCR4 expression confers poor prognosis, whereas inhibition of
      CXCR4 signaling overcomes stroma-mediated chemoresistance in acute myeloid
      leukemia (AML). Here, we demonstrate that treatment with the pan-histone
      deacetylase inhibitor panobinostat (PS) depleted the mRNA and protein levels of
      CXCR4 in the cultured and primary AML cells. PS-induced acetylation of the heat
      shock protein (hsp) 90 reduced the chaperone association between CXCR4 and hsp90,
      directing CXCR4 to degradation by the 20S proteasome. PS treatment also depleted
      G protein-coupled receptor kinase 3, as well as attenuated the phosphorylation of
      AKT and ERK1/2 in AML cells, which was not affected by cotreatment with CXCL12.
      Compared with each agent alone, cotreatment with PS and CXCR4 antagonist AMD3100
      or FC-131 synergistically induced apoptosis of cultured and primary AML cells. PS
      and FC-131 exerted more lethal effects on primary AML versus normal CD34(+) bone
      marrow progenitor cells. These findings support the rationale to test the in vivo
      efficacy of PS in enhancing the lethal effects of CXCR4 antagonists against AML
      cells.

PMID- 20810928
TI  - Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and
      nilotinib.
AB  - Several cancer treatments are shifting from traditional, time-limited,
      nonspecific cytotoxic chemotherapy cycles to continuous oral treatment with
      specific protein-targeted therapies. In this line, imatinib mesylate, a selective
      tyrosine kinases inhibitor (TKI), has excellent efficacy in the treatment of
      chronic myeloid leukemia. It has opened the way to the development of additional
      TKIs against chronic myeloid leukemia, including nilotinib and dasatinib. TKIs
      are prescribed for prolonged periods, often in patients with comorbidities.
      Therefore, they are regularly co-administered along with treatments at risk of
      drug-drug interactions. This aspect has been partially addressed so far, calling
      for a comprehensive review of the published data. We review here the available
      evidence and pharmacologic mechanisms of interactions between imatinib,
      dasatinib, and nilotinib and widely prescribed co-medications, including known
      inhibitors or inducers of cytochromes P450 or drug transporters. Information is
      mostly available for imatinib mesylate, well introduced in clinical practice.
      Several pharmacokinetic aspects yet remain insufficiently investigated for these
      drugs. Regular updates will be mandatory and so is the prospective reporting of
      unexpected clinical observations.

PMID- 20810929
TI  - Prospective assessment of thrombin generation test for dose monitoring of
      bypassing therapy in hemophilia patients with inhibitors undergoing elective
      surgery.
AB  - Clinical response to bypassing agents (BPAs) may vary between patients. Surgery
      is a particular situation, requiring effective hemostasis during the procedure
      and for several days postoperatively to obtain satisfactory wound healing.
      However, the optimal dose of BPA in different surgical situations has not been
      clearly established. We report here a prospective assessment of thrombin
      generation test (TGT) in monitoring the effectiveness of BPA during 10 elective
      invasive procedures performed in 6 patients with severe hemophilia and high-titer
      inhibitors. A standardized 3-step protocol was used in all cases to individually
      tailor BPA. Thrombin-generating capacity of patients increased after in vitro and
      ex vivo addition of BPA in a dose-dependent manner. Our results also showed a
      correlation between in vivo clinical response to BPA and thrombin-generating
      capacity. These data suggest that TGT may represent a surrogate marker for
      monitoring bypassing therapies in surgical situations.

PMID- 20810931
TI  - The role of the orthopaedic surgeon in minimizing mortality and morbidity
      associated with fragility fractures.

PMID- 20810932
TI  - Quality of care: getting from good to great.

PMID- 20810930
TI  - Polymorphisms at LDLR locus may be associated with coronary artery disease
      through modulation of coagulation factor VIII activity and independently from
      lipid profile.
AB  - High levels of coagulation factor VIII (FVIII) have been associated with
      cardiovascular disease. Low-density lipoprotein receptor (LDLR) has been recently
      demonstrated to contribute to FVIII clearance from plasma. The aim of this study
      was to evaluate 3 single nucleotide polymorphisms in SMARCA4-LDLR gene locus
      (rs1122608, rs2228671, and rs688) and FVIII coagulant activity (FVIII:c) in
      subjects with (n = 692) or without (n = 291) angiographically confirmed coronary
      artery disease (CAD). High FVIII:c levels were an independent risk factor for
      CAD. The rs688 and rs2228671 genotypes were predictors of FVIII:c with T alleles
      associated with higher FVIII:c levels. The rs2228671T allele was associated also
      with reduced total and LDL-cholesterol levels. With respect to the risk of CAD,
      no association was found for rs2228671. Consistently with higher FVIII:c levels,
      the rs688T allele was associated with CAD, whereas, consistently with a favorable
      lipid profile, the rs1122608T allele was associated with a decreased CAD
      prevalence. After adjustment for classic cardiovascular risk factors, including
      plasma lipids, rs688 remained associated with CAD (OR for T carriers: 1.67 with
      95% confidence interval, 1.10-2.54). Haplotype analysis confirmed such results.
      Our data suggest that polymorphisms at LDLR locus modulate FVIII:c levels and may
      be associated with CAD risk independently from plasma lipids.

PMID- 20810933
TI  - Noncontact anterior cruciate ligament injuries: mechanisms and risk factors.
AB  - Significant advances have recently been made in understanding the mechanisms
      involved in noncontact anterior cruciate ligament (ACL) injury. Most ACL injuries
      involve minimal to no contact. Female athletes sustain a two- to eightfold
      greater rate of injury than do their male counterparts. Recent videotape analyses
      demonstrate significant differences in average leg and trunk positions during
      injury compared with control subjects. These findings as well as those of
      cadaveric and MRI studies indicate that axial compressive forces are a critical
      component in noncontact ACL injury. A complete understanding of the forces and
      risk factors associated with noncontact ACL injury should lead to the development
      of improved preventive strategies for this devastating injury.

PMID- 20810934
TI  - Guided growth for the correction of pediatric lower limb angular deformity.
AB  - Guided growth is useful in correcting pediatric angular deformities. Although
      growth manipulation has been applied to various deformities, it is most commonly
      used to correct coronal plane deformity about the knee. Temporary
      hemiepiphysiodesis is performed using staples, percutaneous transphyseal screws,
      or a tension band plate. Permanent hemiepiphysiodesis can be done using either an
      open Phemister or a percutaneous approach. These techniques function by tethering
      one side of a growing physis, thereby allowing differential growth. Applied
      correctly, this can also result in angular deformity correction. Undercorrection
      and overcorrection are common problems with guided growth. However, careful
      preoperative planning and appropriate follow-up can minimize complications and
      allow for excellent deformity correction with minimal morbidity.

PMID- 20810935
TI  - Dural tears in spine surgery.
AB  - Dural tears are among the most commonly seen complications in spine surgery. Most
      studies in the literature indicate that long-term outcomes are not negatively
      affected, provided that the tears are diagnosed early and managed appropriately.
      Direct suture repair remains the preferred method for the management of durotomy
      caused by or found during surgery. However, recent literature reports encouraging
      results with sutureless repair. Understanding dural anatomy, dural healing, and
      cerebrospinal fluid dynamics is helpful in choosing among the available
      management options for dural tear.

PMID- 20810936
TI  - Management of common sports-related injuries about the foot and ankle.
AB  - Foot and ankle injuries are commonplace in competitive sports. Improvements in
      injury surveillance programs and injury reporting have enabled physicians to
      better recognize and manage specific foot and ankle injuries, with a primary goal
      of efficient and safe return to play. Athletes are becoming stronger, faster, and
      better conditioned, and higher-energy injuries are becoming increasingly common.
      Close attention is required during examination to accurately identify such
      injuries as turf toe, ankle injuries, tarsometatarsal (ie, Lisfranc) injuries,
      and stress fractures. Early diagnosis and management of these injuries are
      critical. Ultimately, however, pressure to return to play must not compromise
      appropriate care and long-term outcomes.

PMID- 20810937
TI  - Osteochondritis dissecans of the capitellum: current concepts.
AB  - Osteochondritis dissecans (OCD) of the capitellum is an uncommon disorder seen
      primarily in the adolescent overhead athlete. Unlike Panner disease, a self
      limiting condition of the immature capitellum, OCD is multifactorial and likely
      results from microtrauma in the setting of cartilage mismatch and vascular
      susceptibility. The natural history of OCD is poorly understood, and degenerative
      joint disease may develop over time. Multiple modalities aid in diagnosis,
      including radiography, MRI, and magnetic resonance arthrography. Lesion size,
      location, and grade determine management, which should attempt to address
      subchondral bone loss and articular cartilage damage. Early, stable lesions are
      managed with rest. Surgery should be considered for unstable lesions. Most
      investigators advocate arthroscopic debridement with marrow stimulation. Fragment
      fixation and bone grafting also have provided good short-term results, but
      concerns persist regarding the healing potential of advanced lesions.
      Osteochondral autograft transplantation appears to be promising and should be
      reserved for larger, higher grade lesions. Clinical outcomes and return to sport
      are variable. Longer-term follow-up studies are necessary to fully assess
      surgical management, and patients must be counseled appropriately.

PMID- 20810938
TI  - Pressure ulcers in orthopaedics.
AB  - Pressure ulcers can be a devastating complication in the care of orthopaedic
      patients. Their presence leads to increased morbidity, mortality, and cost of
      care. Therapy and rehabilitation cannot progress on a normal postoperative course
      in the patient with a pressure ulcer. Risk factors for the development of
      pressure ulcers include spinal cord injury, advanced age, and cognitive
      impairment. Several grading scales have been developed for the assessment of
      pressure ulcer. Frequent patient turning, close monitoring, and frequent skin
      checks are important factors in the prevention of pressure ulcer.

PMID- 20810939
TI  - Bone void fillers.
AB  - For this technology overview, the tools of evidence-based medicine were used to
      summarize information on the effectiveness and clinical outcomes related to the
      usage of bone void fillers- specifically, synthetic graft materials.
      Comprehensive literature searches were conducted to address five key questions,
      which the task force that prepared the report posed as follows. Question 1
      addressed the use of synthetic bone void fillers alone. Question 2 was designed
      to determine whether synthetic bone void fillers could successfully serve as
      graft extenders and eliminate the need for iliac crest bone graft. Questions 3,
      4, and 5 addressed the use of allografts as a comparison with synthetic fillers
      because clinical results with allografts are perceived as being much closer to
      autografts in these areas of the spine.

PMID- 20810940
TI  - Beyond BIO2010: integrating biology and mathematics: collaborations, challenges,
      and opportunities.

PMID- 20810941
TI  - "Beyond BIO2010: Celebration and Opportunities" at the intersection of
      mathematics and biology.

PMID- 20810943
TI  - Math and data exploration.

PMID- 20810944
TI  - E. Virginia Armbrust. Interviewed by Laura L. Mays Hoopes.

PMID- 20810945
TI  - Order matters: using the 5E model to align teaching with how people learn.

PMID- 20810946
TI  - Toward integration: from quantitative biology to mathbio-biomath?
AB  - In response to the call of BIO2010 for integrating quantitative skills into
      undergraduate biology education, 30 Howard Hughes Medical Institute (HHMI)
      Program Directors at the 2006 HHMI Program Directors Meeting established a
      consortium to investigate, implement, develop, and disseminate best practices
      resulting from the integration of math and biology. With the assistance of an
      HHMI-funded mini-grant, led by Karl Joplin of East Tennessee State University,
      and support in institutional HHMI grants at Emory and University of Delaware,
      these institutions held a series of summer institutes and workshops to document
      progress toward and address the challenges of implementing a more quantitative
      approach to undergraduate biology education. This report summarizes the results
      of the four summer institutes (2007-2010). The group developed four draft white
      papers, a wiki site, and a listserv. One major outcome of these meetings is this
      issue of CBE-Life Sciences Education, which resulted from proposals at our 2008
      meeting and a January 2009 planning session. Many of the papers in this issue
      emerged from or were influenced by these meetings.

PMID- 20810947
TI  - Bioinformatics and the undergraduate curriculum essay.
AB  - Recent advances involving high-throughput techniques for data generation and
      analysis have made familiarity with basic bioinformatics concepts and programs a
      necessity in the biological sciences. Undergraduate students increasingly need
      training in methods related to finding and retrieving information stored in vast
      databases. The rapid rise of bioinformatics as a new discipline has challenged
      many colleges and universities to keep current with their curricula, often in the
      face of static or dwindling resources. On the plus side, many bioinformatics
      modules and related databases and software programs are free and accessible
      online, and interdisciplinary partnerships between existing faculty members and
      their support staff have proved advantageous in such efforts. We present examples
      of strategies and methods that have been successfully used to incorporate
      bioinformatics content into undergraduate curricula.

PMID- 20810948
TI  - BioMaPS: a roadmap for success.
AB  - The manuscript outlines the impact that our National Science Foundation
      Interdisciplinary Training for Undergraduates in Biological and Mathematical
      Sciences program, BioMaPS, has had on the students and faculty at Murray State
      University. This interdisciplinary program teams mathematics and biology
      undergraduate students with mathematics and biology faculty and has produced
      research insights and curriculum developments at the intersection of these two
      disciplines. The goals, structure, achievements, and curriculum initiatives are
      described in relation to the effects they have had to enhance the study of
      biomathematics.

PMID- 20810949
TI  - A transformative model for undergraduate quantitative biology education.
AB  - The BIO2010 report recommended that students in the life sciences receive a more
      rigorous education in mathematics and physical sciences. The University of
      Delaware approached this problem by (1) developing a bio-calculus section of a
      standard calculus course, (2) embedding quantitative activities into existing
      biology courses, and (3) creating a new interdisciplinary major, quantitative
      biology, designed for students interested in solving complex biological problems
      using advanced mathematical approaches. To develop the bio-calculus sections, the
      Department of Mathematical Sciences revised its three-semester calculus sequence
      to include differential equations in the first semester and, rather than using
      examples traditionally drawn from application domains that are most relevant to
      engineers, drew models and examples heavily from the life sciences. The
      curriculum of the B.S. degree in Quantitative Biology was designed to provide
      students with a solid foundation in biology, chemistry, and mathematics, with an
      emphasis on preparation for research careers in life sciences. Students in the
      program take core courses from biology, chemistry, and physics, though
      mathematics, as the cornerstone of all quantitative sciences, is given particular
      prominence. Seminars and a capstone course stress how the interplay of
      mathematics and biology can be used to explain complex biological systems. To
      initiate these academic changes required the identification of barriers and the
      implementation of solutions.

PMID- 20810950
TI  - Mathematics, thermodynamics, and modeling to address ten common misconceptions
      about protein structure, folding, and stability.
AB  - To fully understand the roles proteins play in cellular processes, students need
      to grasp complex ideas about protein structure, folding, and stability. Our
      current understanding of these topics is based on mathematical models and
      experimental data. However, protein structure, folding, and stability are often
      introduced as descriptive, qualitative phenomena in undergraduate classes. In the
      process of learning about these topics, students often form incorrect ideas. For
      example, by learning about protein folding in the context of protein synthesis,
      students may come to an incorrect conclusion that once synthesized on the
      ribosome, a protein spends its entire cellular life time in its fully folded
      native confirmation. This is clearly not true; proteins are dynamic structures
      that undergo both local fluctuations and global unfolding events. To prevent and
      address such misconceptions, basic concepts of protein science can be introduced
      in the context of simple mathematical models and hands-on explorations of
      publicly available data sets. Ten common misconceptions about proteins are
      presented, along with suggestions for using equations, models, sequence,
      structure, and thermodynamic data to help students gain a deeper understanding of
      basic concepts relating to protein structure, folding, and stability.

PMID- 20810951
TI  - Connecting biology and mathematics: first prepare the teachers.
AB  - Developing the connection between biology and mathematics is one of the most
      important ways to shift the paradigms of both established science disciplines.
      However, adding some mathematic content to biology or biology content to
      mathematics is not enough but must be accompanied by development of suitable
      pedagogical models. I propose a model of pedagogical mathematical biological
      content knowledge as a feasible starting point for connecting biology and
      mathematics in schools and universities. The process of connecting these
      disciplines should start as early as possible in the educational process, in
      order to produce prepared minds that will be able to combine both disciplines at
      graduate and postgraduate levels of study. Because teachers are a crucial factor
      in introducing innovations in education, the first step toward such a goal should
      be the education of prospective and practicing elementary and secondary school
      teachers.

PMID- 20810952
TI  - Mathematical manipulative models: in defense of "beanbag biology".
AB  - Mathematical manipulative models have had a long history of influence in
      biological research and in secondary school education, but they are frequently
      neglected in undergraduate biology education. By linking mathematical
      manipulative models in a four-step process-1) use of physical manipulatives, 2)
      interactive exploration of computer simulations, 3) derivation of mathematical
      relationships from core principles, and 4) analysis of real data sets-we
      demonstrate a process that we have shared in biological faculty development
      workshops led by staff from the BioQUEST Curriculum Consortium over the past 24
      yr. We built this approach based upon a broad survey of literature in
      mathematical educational research that has convincingly demonstrated the utility
      of multiple models that involve physical, kinesthetic learning to actual data and
      interactive simulations. Two projects that use this approach are introduced: The
      Biological Excel Simulations and Tools in Exploratory, Experiential Mathematics
      (ESTEEM) Project (http://bioquest.org/esteem) and Numerical Undergraduate
      Mathematical Biology Education (NUMB3R5 COUNT; http://bioquest.org/numberscount).
      Examples here emphasize genetics, ecology, population biology, photosynthesis,
      cancer, and epidemiology. Mathematical manipulative models help learners break
      through prior fears to develop an appreciation for how mathematical reasoning
      informs problem solving, inference, and precise communication in biology and
      enhance the diversity of quantitative biology education.

PMID- 20810953
TI  - Impact of Interdisciplinary Undergraduate Research in mathematics and biology on
      the development of a new course integrating five STEM disciplines.
AB  - Funded by innovative programs at the National Science Foundation and the Howard
      Hughes Medical Institute, University of Richmond faculty in biology, chemistry,
      mathematics, physics, and computer science teamed up to offer first- and second
      year students the opportunity to contribute to vibrant, interdisciplinary
      research projects. The result was not only good science but also good science
      that motivated and informed course development. Here, we describe four recent
      undergraduate research projects involving students and faculty in biology,
      physics, mathematics, and computer science and how each contributed in
      significant ways to the conception and implementation of our new Integrated
      Quantitative Science course, a course for first-year students that integrates the
      material in the first course of the major in each of biology, chemistry,
      mathematics, computer science, and physics.

PMID- 20810954
TI  - Enhancing interdisciplinary mathematics and biology education: a microarray data
      analysis course bridging these disciplines.
AB  - BIO2010 put forth the goal of improving the mathematical educational background
      of biology students. The analysis and interpretation of microarray high
      dimensional data can be very challenging and is best done by a statistician and a
      biologist working and teaching in a collaborative manner. We set up such a
      collaboration and designed a course on microarray data analysis. We started using
      Genome Consortium for Active Teaching (GCAT) materials and Microarray Genome and
      Clustering Tool software and added R statistical software along with Bioconductor
      packages. In response to student feedback, one microarray data set was fully
      analyzed in class, starting from preprocessing to gene discovery to pathway
      analysis using the latter software. A class project was to conduct a similar
      analysis where students analyzed their own data or data from a published journal
      paper. This exercise showed the impact that filtering, preprocessing, and
      different normalization methods had on gene inclusion in the final data set. We
      conclude that this course achieved its goals to equip students with skills to
      analyze data from a microarray experiment. We offer our insight about
      collaborative teaching as well as how other faculty might design and implement a
      similar interdisciplinary course.

PMID- 20810955
TI  - Mathematical biology modules based on modern molecular biology and modern
      discrete mathematics.
AB  - We describe an ongoing collaborative curriculum materials development project
      between Sweet Briar College and Western Michigan University, with support from
      the National Science Foundation. We present a collection of modules under
      development that can be used in existing mathematics and biology courses, and we
      address a critical national need to introduce students to mathematical methods
      beyond the interface of biology with calculus. Based on ongoing research, and
      designed to use the project-based-learning approach, the modules highlight
      applications of modern discrete mathematics and algebraic statistics to pressing
      problems in molecular biology. For the majority of projects, calculus is not a
      required prerequisite and, due to the modest amount of mathematical background
      needed for some of the modules, the materials can be used for an early
      introduction to mathematical modeling. At the same time, most modules are
      connected with topics in linear and abstract algebra, algebraic geometry, and
      probability, and they can be used as meaningful applied introductions into the
      relevant advanced-level mathematics courses. Open-source software is used to
      facilitate the relevant computations. As a detailed example, we outline a module
      that focuses on Boolean models of the lac operon network.

PMID- 20810956
TI  - An initiative to broaden diversity in undergraduate biomathematics training.
AB  - At North Carolina A&T State University (NCATSU), there was a critical need to
      better coordinate genuine research and classroom experiences for undergraduates
      early in their academic career. We describe the development and implementation of
      a faculty alliance across academic departments to increase biomathematics
      research opportunities for underrepresented minorities. Our faculty alliance is
      called the Integrative Biomathematical Learning and Empowerment Network for
      Diversity (iBLEND). The fundamental purpose of the iBLEND alliance was to inspire
      underrepresented minorities to pursue research careers by increasing the
      visibility of research conducted at the interface of mathematics and biology at
      NCATSU. Because of the many positive impacts, iBLEND gained significant buy-in
      from administration, faculty, and students by 1) working from the ground up with
      administration to promote campus-wide biomathematics research and training, 2)
      fostering associations between research and regular undergraduate academic
      courses, 3) creating and disseminating biomathematics teaching and learning
      modules, and 4) enhancing learning community support at the interface of
      mathematics and biology. Currently, iBLEND is viewed as a productive site for
      graduate schools to recruit underrepresented minority students having specific
      competencies related to mathematical biology.

PMID- 20810957
TI  - From biology to mathematical models and back: teaching modeling to biology
      students, and biology to math and engineering students.
AB  - We describe the development of a course to teach modeling and mathematical
      analysis skills to students of biology and to teach biology to students with
      strong backgrounds in mathematics, physics, or engineering. The two groups of
      students have different ways of learning material and often have strong negative
      feelings toward the area of knowledge that they find difficult. To give students
      a sense of mastery in each area, several complementary approaches are used in the
      course: 1) a "live" textbook that allows students to explore models and
      mathematical processes interactively; 2) benchmark problems providing key skills
      on which students make continuous progress; 3) assignment of students to teams of
      two throughout the semester; 4) regular one-on-one interactions with instructors
      throughout the semester; and 5) a term project in which students reconstruct,
      analyze, extend, and then write in detail about a recently published biological
      model. Based on student evaluations and comments, an attitude survey, and the
      quality of the students' term papers, the course has significantly increased the
      ability and willingness of biology students to use mathematical concepts and
      modeling tools to understand biological systems, and it has significantly
      enhanced engineering students' appreciation of biology.

PMID- 20810958
TI  - Evaluating a modeling curriculum by using heuristics for productive disciplinary
      engagement.
AB  - The BIO2010 report provided a compelling argument for the need to create learning
      experiences for undergraduate biology students that are more authentic to modern
      science. The report acknowledged the need for research that could help
      practitioners successfully create and reform biology curricula with this goal in
      mind. Our objective in this article was to explore how a set of six design
      heuristics could be used to evaluate the potential of curricula to support
      productive learning experiences for science students. We drew on data collected
      during a long-term study of an undergraduate traineeship that introduced students
      to mathematical modeling in the context of modern biological problems. We present
      illustrative examples from this curriculum that highlight the ways in which three
      heuristics-instructor role-modeling, holding students to scientific norms, and
      providing students with opportunities to practice these norms-consistently
      supported learning across the curriculum. We present a more detailed comparison
      of two different curricular modules and explain how differences in student
      authority, problem structure, and access to resources contributed to differences
      in productive engagement by students in these modules. We hope that our analysis
      will help practitioners think in more concrete terms about how to achieve the
      goals set forth by BIO2010.

PMID- 20810959
TI  - Online interactive teaching modules enhance quantitative proficiency of
      introductory biology students.
AB  - There is widespread agreement within the scientific and education communities
      that undergraduate biology curricula fall short in providing students with the
      quantitative and interdisciplinary problem-solving skills they need to obtain a
      deep understanding of biological phenomena and be prepared fully to contribute to
      future scientific inquiry. MathBench Biology Modules were designed to address
      these needs through a series of interactive, Web-based modules that can be used
      to supplement existing course content across the biological sciences curriculum.
      The effect of the modules was assessed in an introductory biology course at the
      University of Maryland. Over the course of the semester, students showed
      significant increases in quantitative skills that were independent of previous
      math course work. Students also showed increased comfort with solving
      quantitative problems, whether or not they ultimately arrived at the correct
      answer. A survey of spring 2009 graduates indicated that those who had
      experienced MathBench in their course work had a greater appreciation for the
      role of mathematics in modern biology than those who had not used MathBench.
      MathBench modules allow students from diverse educational backgrounds to hone
      their quantitative skills, preparing them for more complex mathematical
      approaches in upper-division courses.

PMID- 20810960
TI  - Interdisciplinary training in mathematical biology through team-based
      undergraduate research and courses.
AB  - Inspired by BIO2010 and leveraging institutional and external funding, Truman
      State University built an undergraduate program in mathematical biology with high
      quality, faculty-mentored interdisciplinary research experiences at its core.
      These experiences taught faculty and students to bridge the epistemological gap
      between the mathematical and life sciences. Together they created the
      infrastructure that currently supports several interdisciplinary courses, an
      innovative minor degree, and long-term interdepartmental research collaborations.
      This article describes how the program was built with support from the National
      Science Foundation's Interdisciplinary Training for Undergraduates in Biology and
      Mathematics program, and it shares lessons learned that will help other
      undergraduate institutions build their own program.

PMID- 20810961
TI  - Using the principles of BIO2010 to develop an introductory, interdisciplinary
      course for biology students.
AB  - Modern biological sciences require practitioners to have increasing levels of
      knowledge, competence, and skills in mathematics and programming. A recent review
      of the science curriculum at the University of Queensland, a large, research
      intensive institution in Australia, resulted in the development of a more
      quantitatively rigorous undergraduate program. Inspired by the National Research
      Council's BIO2010 report, a new interdisciplinary first-year course (SCIE1000)
      was created, incorporating mathematics and computer programming in the context of
      modern science. In this study, the perceptions of biological science students
      enrolled in SCIE1000 in 2008 and 2009 are measured. Analysis indicates that, as a
      result of taking SCIE1000, biological science students gained a positive
      appreciation of the importance of mathematics in their discipline. However, the
      data revealed that SCIE1000 did not contribute positively to gains in
      appreciation for computing and only slightly influenced students' motivation to
      enroll in upper-level quantitative-based courses. Further comparisons between
      2008 and 2009 demonstrated the positive effect of using genuine, real-world
      contexts to enhance student perceptions toward the relevance of mathematics. The
      results support the recommendation from BIO2010 that mathematics should be
      introduced to biology students in first-year courses using real-world examples,
      while challenging the benefits of introducing programming in first-year courses.

PMID- 20810962
TI  - On a calculus-based statistics course for life science students.
AB  - The choice of pedagogy in statistics should take advantage of the quantitative
      capabilities and scientific background of the students. In this article, we
      propose a model for a statistics course that assumes student competency in
      calculus and a broadening knowledge in biology. We illustrate our methods and
      practices through examples from the curriculum.

PMID- 20810963
TI  - Preparing the "new" biologist of the future: student research at the interface of
      mathematics and biology.
AB  - We describe a unique Research Experience for Undergraduates and Research
      Experience for Veterinary students summer program at the National Institute for
      Mathematical and Biological Synthesis on the campus of the University of
      Tennessee, Knoxville. The program focused on interdisciplinary research at the
      interface of biology and mathematics. Participants were selected to work on
      projects with a biology mentor and a mathematics mentor in an environment that
      promoted collaboration outside of the students' respective disciplines. There
      were four research projects with teams of four participants and two faculty
      mentors. The participants consisted of a mixture of 10 undergraduates in biology-
      and mathematics-related disciplines, four veterinary students, and two high
      school teachers. The activities included lectures on both the biological and
      mathematical backgrounds of the projects, tutorials for software, and sessions on
      ethics, graduate school, and possible career paths for individuals interested in
      biology and mathematics. The program was designed to give students the ability to
      actively participate in the scientific research process by working on a project,
      writing up their results in a final report, and presenting their work orally. We
      report on the results of our evaluation surveys of the participants.

PMID- 20810964
TI  - Team research at the biology-mathematics interface: project management
      perspectives.
AB  - The success of interdisciplinary research teams depends largely upon skills
      related to team performance. We evaluated student and team performance for
      undergraduate biology and mathematics students who participated in summer
      research projects conducted in off-campus laboratories. The student teams were
      composed of a student with a mathematics background and an experimentally
      oriented biology student. The team mentors typically ranked the students'
      performance very good to excellent over a range of attributes that included
      creativity and ability to conduct independent research. However, the research
      teams experienced problems meeting prespecified deadlines due to poor time and
      project management skills. Because time and project management skills can be
      readily taught and moreover typically reflect good research practices, simple
      modifications should be made to undergraduate curricula so that the promise of
      initiatives, such as MATH-BIO 2010, can be implemented.

PMID- 20810965
TI  - 1, 2, 3, 4: infusing quantitative literacy into introductory biology.
AB  - Biology of the twenty-first century is an increasingly quantitative science.
      Undergraduate biology education therefore needs to provide opportunities for
      students to develop fluency in the tools and language of quantitative
      disciplines. Quantitative literacy (QL) is important for future scientists as
      well as for citizens, who need to interpret numeric information and data-based
      claims regarding nearly every aspect of daily life. To address the need for QL in
      biology education, we incorporated quantitative concepts throughout a semester
      long introductory biology course at a large research university. Early in the
      course, we assessed the quantitative skills that students bring to the
      introductory biology classroom and found that students had difficulties in
      performing simple calculations, representing data graphically, and articulating
      data-driven arguments. In response to students' learning needs, we infused the
      course with quantitative concepts aligned with the existing course content and
      learning objectives. The effectiveness of this approach is demonstrated by
      significant improvement in the quality of students' graphical representations of
      biological data. Infusing QL in introductory biology presents challenges. Our
      study, however, supports the conclusion that it is feasible in the context of an
      existing course, consistent with the goals of college biology education, and
      promotes students' development of important quantitative skills.

PMID- 20810966
TI  - How to build a course in mathematical-biological modeling: content and processes
      for knowledge and skill.
AB  - Biological problems in the twenty-first century are complex and require
      mathematical insight, often resulting in mathematical models of biological
      systems. Building mathematical-biological models requires cooperation among
      biologists and mathematicians, and mastery of building models. A new course in
      mathematical modeling presented the opportunity to build both content and process
      learning of mathematical models, the modeling process, and the cooperative
      process. There was little guidance from the literature on how to build such a
      course. Here, I describe the iterative process of developing such a course,
      beginning with objectives and choosing content and process competencies to
      fulfill the objectives. I include some inductive heuristics for instructors
      seeking guidance in planning and developing their own courses, and I illustrate
      with a description of one instructional model cycle. Students completing this
      class reported gains in learning of modeling content, the modeling process, and
      cooperative skills. Student content and process mastery increased, as assessed on
      several objective-driven metrics in many types of assessments.

PMID- 20810967
TI  - SYMBIOSIS: development, implementation, and assessment of a model curriculum
      across biology and mathematics at the introductory level.
AB  - "It takes a lot of courage to release the familiar and seemingly secure, to
      embrace the new. But there is no real security in what is no longer meaningful.
      There is more security in the adventurous and exciting, for in movement there is
      life, and in change there is power." Alan Cohen (Used by permission. All rights
      reserved. For more information on Alan Cohen's books and programs, see
      (www.alancohen.com.) With the support of the East Tennessee State University
      (ETSU) administration and a grant from Howard Hughes Medical Institute, the
      departments of Biological Sciences, Mathematics and Statistics, and Curriculum
      and Instruction have developed a biology-math integrated curriculum. An
      interdisciplinary faculty team, charged with teaching the 18 curriculum modules,
      designed this three-semester curriculum, known as SYMBIOSIS. This curriculum was
      piloted to two student cohorts during the developmental stage. The positive
      feedback and assessment results of this project have given us the foundation to
      implement the SYMBIOSIS curriculum as a replacement for the standard biology
      majors curriculum at the introductory level. This article addresses the history
      and development of the curriculum, previous assessment results and current
      assessment protocol, and the future of ETSU's approach to implementing the
      SYMBIOSIS curriculum.

PMID- 20810969
TI  - Computer literacy for life sciences: helping the digital-era biology
      undergraduates face today's research.
AB  - Computer literacy plays a critical role in today's life sciences research.
      Without the ability to use computers to efficiently manipulate and analyze large
      amounts of data resulting from biological experiments and simulations, many of
      the pressing questions in the life sciences could not be answered. Today's
      undergraduates, despite the ubiquity of computers in their lives, seem to be
      largely unfamiliar with how computers are being used to pursue and answer such
      questions. This article describes an innovative undergraduate-level course,
      titled Computer Literacy for Life Sciences, that aims to teach students the
      basics of a computerized scientific research pursuit. The purpose of the course
      is for students to develop a hands-on working experience in using standard
      computer software tools as well as computer techniques and methodologies used in
      life sciences research. This paper provides a detailed description of the
      didactical tools and assessment methods used in and outside of the classroom as
      well as a discussion of the lessons learned during the first installment of the
      course taught at Emory University in fall semester 2009.

PMID- 20810968
TI  - RNA secondary structure prediction by using discrete mathematics: an
      interdisciplinary research experience for undergraduate students.
AB  - The focus of this Research Experience for Undergraduates (REU) project was on RNA
      secondary structure prediction by using a lattice walk approach. The lattice walk
      approach is a combinatorial and computational biology method used to enumerate
      possible secondary structures and predict RNA secondary structure from RNA
      sequences. The method uses discrete mathematical techniques and identifies
      specified base pairs as parameters. The goal of the REU was to introduce upper
      level undergraduate students to the principles and challenges of
      interdisciplinary research in molecular biology and discrete mathematics. At the
      beginning of the project, students from the biology and mathematics departments
      of a mid-sized university received instruction on the role of secondary structure
      in the function of eukaryotic RNAs and RNA viruses, RNA related to combinatorics,
      and the National Center for Biotechnology Information resources. The student
      research projects focused on RNA secondary structure prediction on a regulatory
      region of the yellow fever virus RNA genome and on an untranslated region of an
      mRNA of a gene associated with the neurological disorder epilepsy. At the end of
      the project, the REU students gave poster and oral presentations, and they
      submitted written final project reports to the program director. The outcome of
      the REU was that the students gained transferable knowledge and skills in
      bioinformatics and an awareness of the applications of discrete mathematics to
      biological research problems.

PMID- 20810970
TI  - Developing student collaborations across disciplines, distances, and
      institutions.
AB  - Because quantitative biology requires skills and concepts from a disparate
      collection of different disciplines, the scientists of the near future will
      increasingly need to rely on collaborations to produce results. Correspondingly,
      students in disciplines impacted by quantitative biology will need to be taught
      how to create and engage in such collaborations. In response to this important
      curricular need, East Tennessee State University and Georgia Technological
      University/Emory University cooperated in an unprecedented curricular experiment
      in which theoretically oriented students at East Tennessee State designed
      biophysical models that were implemented and tested experimentally by biomedical
      engineers at the Wallace H. Coulter Department of Biomedical Engineering at
      Georgia Technological University and Emory University. Implementing the
      collaborations between two institutions allowed an assessment of the student
      collaborations from before the groups of students had met for the first time
      until after they had finished their projects, thus providing insight about the
      formation and conduct of such collaborations that could not have been obtained
      otherwise.

PMID- 20810971
TI  - Introductory life science mathematics and quantitative neuroscience courses.
AB  - We describe two sets of courses designed to enhance the mathematical,
      statistical, and computational training of life science undergraduates at Emory
      College. The first course is an introductory sequence in differential and
      integral calculus, modeling with differential equations, probability, and
      inferential statistics. The second is an upper-division course in computational
      neuroscience. We provide a description of each course, detailed syllabi, examples
      of content, and a brief discussion of the main issues encountered in developing
      and offering the courses.

PMID- 20810972
TI  - Relation of food cost to healthfulness of diet among US women.
AB  - BACKGROUND: Few studies have evaluated the cost of a diet that may prevent
      cardiovascular disease. High scores on the Alternative Healthy Eating Index
      (AHEI) have been associated with lower rates of cardiovascular disease.
      OBJECTIVE: We sought to evaluate the cost of a dietary pattern that may prevent
      cardiovascular disease among women residing in the United States. DESIGN: By
      using food-cost data from the US Department of Agriculture, we explored relations
      between spending on food and AHEI scores among 78,191 participants in the Nurses'
      Health Study. By using linear regression, we estimated the change in AHEI score
      (range: 2.5-87.5) for a $1 increase in spending on various food groups. RESULTS:
      Study participants in the highest energy-adjusted spending quintile spent 124% as
      much money each day as those in the lowest quintile. The difference in AHEI
      scores (10th-90th percentile) between all study participants was 30 index points
      (Spearman's correlation coefficient between total spending and AHEI = 0.44). The
      difference in AHEI scores (10th-90th percentile) within each quintile of spending
      ranged from 25 to 29 index points. Greater spending on nuts, soy and beans, and
      whole grains was associated with a higher AHEI score. Greater spending on red and
      processed meats and high-fat dairy was associated with a lower AHEI score.
      CONCLUSIONS: Although spending more money was associated with a healthier diet,
      large improvements in diet may be achieved without increased spending. The
      purchase of plant-based foods may offer the best investment for dietary health.

PMID- 20810973
TI  - Associations between energy demands, physical activity, and body composition in
      adult humans between 18 and 96 y of age.
AB  - BACKGROUND: Associations between body composition and the energy expended on
      basal metabolism and activity are complex and age dependent. OBJECTIVE: The
      objective was to examine associations between body composition and daily (DEE),
      basal (BEE), and activity energy expenditure (AEE) throughout the adult life
      span. DESIGN: A cross-sectional study was conducted in 529 adults aged 18-96 y.
      DEE was measured by using doubly labeled water, BEE by using respirometry, and
      body composition by isotope dilution. AEE was calculated as DEE - BEE, and
      physical activity level (PAL) was calculated as DEE/BEE. RESULTS: Up to age 52 y,
      fat-free mass (FFM) and fat mass (FM) were positively associated with age in men,
      but no significant effect was observed in women. No effects of age on DEE and AEE
      were observed. The average DEE in men (14.1 MJ/d) was 27% greater than that in
      women (10.7 MJ/d). PAL averaged 1.84 in men and 1.75 in women. Above and
      including the age of 52 y, FFM, FM, DEE, BEE, and AEE were all negatively
      associated with greater age. The effect of age on AEE was greater than on BEE;
      consequently, PAL by the age of 95 y was only 1.36. PAL and AEE were both
      unrelated to FFM (both age adjusted). CONCLUSIONS: PAL and AEE were not
      associated with age in subjects aged <52 y. AEE, BEE, and PAL were all negatively
      associated with age in subjects aged >=52 y. An absence of a relation between age
      adjusted PAL and FFM suggested that greater physical activity was not associated
      with higher FFM in the elderly.

PMID- 20810974
TI  - Dietary glycemic load and type 2 diabetes: modeling the glucose-raising potential
      of carbohydrates for prevention.

PMID- 20810976
TI  - Accruing evidence on benefits of adherence to the Mediterranean diet on health:
      an updated systematic review and meta-analysis.
AB  - BACKGROUND: The Mediterranean diet has long been reported to be protective
      against the occurrence of several different health outcomes. OBJECTIVE: We aimed
      to update our previous meta-analysis of published cohort prospective studies that
      investigated the effects of adherence to the Mediterranean diet on health status.
      DESIGN: We conducted a comprehensive literature search through electronic
      databases up to June 2010. RESULTS: The updated review process showed 7
      prospective studies published in the past 2 y that were not included in the
      previous meta-analysis (1 study for overall mortality, 3 studies for
      cardiovascular incidence or mortality, 1 study for cancer incidence or mortality,
      and 2 studies for neurodegenerative diseases). These recent studies included 2
      health outcomes not previously investigated (ie, mild cognitive impairment and
      stroke). The meta-analysis for all studies with a random-effects model that was
      conducted after the inclusion of these recent studies showed that a 2-point
      increase in adherence to the Mediterranean diet was associated with a significant
      reduction of overall mortality [relative risk (RR) = 0.92; 95% CI: 0.90, 0.94],
      cardiovascular incidence or mortality (RR = 0.90; 95% CI: 0.87, 0.93), cancer
      incidence or mortality (RR = 0.94; 95% CI: 0.92, 0.96), and neurodegenerative
      diseases (RR = 0.87; 95% CI: 0.81, 0.94). The meta-regression analysis showed
      that sample size was the most significant contributor to the model because it
      significantly influenced the estimate of the association for overall mortality.
      CONCLUSION: This updated meta-analysis confirms, in a larger number of subjects
      and studies, the significant and consistent protection provided by adherence to
      the Mediterranean diet in relation to the occurrence of major chronic
      degenerative diseases.

PMID- 20810975
TI  - Mediterranean dietary patterns and prospective weight change in participants of
      the EPIC-PANACEA project.
AB  - BACKGROUND: There is an association between a greater adherence to a
      Mediterranean diet and a reduced risk of developing chronic diseases. However, it
      is not clear whether this dietary pattern may be protective also against the
      development of obesity. OBJECTIVE: We assessed the association between the
      adherence to the Mediterranean dietary pattern (MDP), prospective weight change,
      and the incidence of overweight or obesity. DESIGN: We conducted a prospective
      cohort study [the European Prospective Investigation into Cancer and Nutrition
      Physical Activity, Nutrition, Alcohol Consumption, Cessation of Smoking, Eating
      Out of Home, and Obesity (EPIC-PANACEA) project] in 373,803 individuals (103,455
      men and 270,348 women; age range: 25-70 y) from 10 European countries.
      Anthropometric measurements were obtained at recruitment and after a median
      follow-up time of 5 y. The relative Mediterranean Diet Score (rMED; score range:
      0-18) was used to assess adherence to the MDP according to the consumption of 9
      dietary components that are characteristic of the Mediterranean diet. The
      association between the rMED and 5-y weight change was modeled through
      multiadjusted mixed-effects linear regression. RESULTS: Individuals with a high
      adherence to the MDP according to the rMED (11-18 points) showed a 5-y weight
      change of -0.16 kg (95% CI: -0.24, -0.07 kg) and were 10% (95% CI: 4%, 18%) less
      likely to develop overweight or obesity than were individuals with a low
      adherence to the MDP (0-6 points). The low meat content of the Mediterranean diet
      seemed to account for most of its positive effect against weight gain.
      CONCLUSION: This study shows that promoting the MDP as a model of healthy eating
      may help to prevent weight gain and the development of obesity.

PMID- 20810977
TI  - Vitamin A equivalence of the beta-carotene in beta-carotene-biofortified maize
      porridge consumed by women.
AB  - BACKGROUND: beta-Carotene-biofortified maize is being developed through plant
      breeding as a sustainable agronomic approach to alleviate vitamin A deficiency.
      OBJECTIVE: Our objective was to quantify the vitamin A equivalence of the beta
      carotene in beta-carotene-biofortified maize based on consumption of a single
      serving of maize porridge. DESIGN: Six healthy women each consumed three 250-g
      portions of maize porridge as follows: 1) beta-carotene-biofortified maize
      porridge containing 527 MUg (0.98 MUmol) total beta-carotene, 2) white maize
      porridge with a beta-carotene reference dose containing 595 MUg (1.11 MUmol)
      added beta-carotene, and 3) white maize porridge with a vitamin A reference dose
      containing 286 MUg retinol activity equivelent (1.00 MUmol) added retinyl
      palmitate. Each portion contained 8.0 g added sunflower oil. The porridges were
      consumed in random order separated by >=2 wk. Blood samples were collected over 9
      h. Retinyl palmitate was analyzed in plasma triacylglycerol-rich lipoprotein
      (TRL) fractions by HPLC with coulometric array electrochemical detection.
      RESULTS: Mean (+/- SD) areas under the curve for retinyl palmitate in the TRL
      fractions (nmol ? h) were 24.0 +/- 9.4, 89.7 +/- 34.7, and 80.1 +/- 24.8 after
      ingestion of the beta-carotene-biofortified maize porridge, the white maize
      porridge with the beta-carotene reference dose, and the white maize porridge with
      the vitamin A reference dose, respectively. On average, 6.48 +/- 3.51 MUg (mean
      +/- SD) of the beta-carotene in beta-carotene-biofortified maize porridge and
      2.34 +/- 1.61 MUg of the beta-carotene in the reference dose were each equivalent
      to 1 MUg retinol. CONCLUSION: beta-Carotene in biofortified maize has good
      bioavailability as a plant source of vitamin A.

PMID- 20810978
TI  - Vitamin D2 and vitamin D3 comparisons: fundamentally flawed study methodology.

PMID- 20810979
TI  - Dairy calcium intake, serum vitamin D, and successful weight loss.
AB  - BACKGROUND: The role of dairy calcium intake and serum vitamin D concentrations
      in weight loss is controversial. OBJECTIVE: The objective was to assess the
      association of dairy calcium intake and serum vitamin D with weight loss. DESIGN:
      We analyzed data from participants in the 2-y Dietary Intervention Randomized
      Controlled Trial (DIRECT) [n = 322; mean body mass index (BMI; in kg/m2): 31;
      mean age: 52 y]. A representative sample (n = 126) was followed for 6 mo for
      serum vitamin D changes. RESULTS: Baseline serum 25-hydroxyvitamin D [25(OH)D]
      concentrations decreased significantly across the tertiles of baseline BMI (25.6
      +/- 8.0, 24.1 +/- 8.9, and 22.9 +/- 6.8 ng/mL, respectively; P for trend = 0.02).
      Baseline concentrations of vitamin D and dairy calcium intake were not associated
      with subsequent weight loss. However, in repeated-measures models adjusted for
      age, sex, baseline BMI, total fat intake, and diet group assignment, higher 6-mo
      tertile levels of dairy calcium intake (median for tertiles: 156.5, 358.0, and
      582.9 mg/d, respectively) and serum 25(OH)D (14.5, 21.2, and 30.2 ng/mL,
      respectively) were associated with increased weight loss across the 2-y
      intervention (-3.3, -3.5, and -5.3 kg, respectively, for dairy calcium; P =
      0.043; -3.1, -3.8, and -5.6 kg, respectively, for vitamin D; P = 0.013). In a
      multivariate logistic regression adjusted simultaneously for age, sex, baseline
      BMI, total fat intake, diet group, vitamin D concentration, and dairy calcium, an
      increase of 1 SD in dairy calcium intake increased the likelihood of weight loss
      of >4.5 kg in the preceding 6 mo [odds ratio (OR): 1.45; P = 0.046]. A similar
      increase was seen for serum 25(OH)D at the 6-mo point (OR: 1.7; P = 0.009).
      CONCLUSION: Our study suggests that both higher dairy calcium intake and
      increased serum vitamin D are related to greater diet-induced weight loss. This
      trial was registered at clinicaltrials.gov as NCT00160108.

PMID- 20810980
TI  - Urinary metabolites as biomarkers of polyphenol intake in humans: a systematic
      review.
AB  - BACKGROUND: To identify associations between polyphenol intake and health and
      disease outcomes in cohort studies, it is important to identify biomarkers of
      intake for the various compounds commonly consumed as part of the diet.
      OBJECTIVE: The objective of this systematic review was to assess the usefulness
      of polyphenol metabolites excreted in urine as biomarkers of polyphenol intake in
      humans. DESIGN: The method included a structured search strategy for polyphenol
      intervention studies on Ovid MEDLINE, EMBASE (Ovid), and Cochrane databases;
      formal inclusion and exclusion criteria; data extraction into an Access database;
      validity assessment; and meta-analysis. RESULTS: One hundred sixty-two controlled
      intervention studies with polyphenols were included, and mean recovery yield and
      correlations with the dose ingested were determined for 40 polyphenols.
      Polyphenols such as daidzein, genistein, glycitein, enterolactone, and
      hydroxytyrosol showed both a high recovery yield (12-37%) and a high correlation
      with the dose (Pearson's correlation coefficients: 0.67-0.87), which showed good
      sensitivity and robustness as biomarkers of intake throughout the different
      studies. Weaker recovery for anthocyanins (0.06-0.2%) and weaker correlations
      with dose [Pearson's correlation coefficients: 0.21-0.52 for hesperidin,
      naringenin, (-)-epicatechin, (-)-epigallocatechin, quercetin, and 3 microbial
      metabolites of isoflavones (dihydrodaidzein, equol, and O-desmethylangolensin)]
      suggest that they are currently less suitable as biomarkers of intake.
      CONCLUSIONS: These data confirm the value of certain urinary polyphenols as
      biomarkers of intake. A validation in populations is now needed to evaluate their
      specificity, sensitivity, and responsiveness to dose under free-living
      conditions.

PMID- 20810982
TI  - Cutting edge: Increased IL-17-secreting T cells in children with new-onset type 1
      diabetes.
AB  - CD4(+)FOXP3(+) regulatory T cells are essential for immune tolerance, and murine
      studies suggest that their dysfunction can lead to type 1 diabetes (T1D). Human
      studies assessing regulatory T cell dysfunction in T1D have relied on analysis of
      FOXP3-expressing cells. Recently, distinct subsets of CD4(+)FOXP3(+) T cells with
      differing function were identified. Notably, CD45RA(-)CD25(int)FOXP3(low) T cells
      lack suppressive function and secrete the proinflammatory cytokine IL-17.
      Therefore, we evaluated whether the relative fractions of CD4(+)FOXP3(+) subsets
      are altered in new-onset T1D subjects. We report that children with new-onset T1D
      have an increased proportion of CD45RA(-)CD25(int)FOXP3(low) cells that are not
      suppressive and secrete significantly more IL-17 than other FOXP3(+) subsets.
      Moreover, these T1D subjects had a higher proportion of both CD4(+) and CD8(+) T
      cells that secrete IL-17. The bias toward IL-17-secreting T cells in T1D suggests
      a role for this proinflammatory cytokine in the pathogenesis of disease.

PMID- 20810981
TI  - Divergent motifs but overlapping binding repertoires of six HLA-DQ molecules
      frequently expressed in the worldwide human population.
AB  - Knowledge of the binding repertoires and specificities of HLA-DQ molecules is
      somewhat limited and contradictory, partly because of the scarcity of reports
      addressing some of the most common molecules and possibly because of the
      diversity of the techniques used. In this paper, we report the development of
      high-throughput binding assays for the six most common DQ molecules in the
      general worldwide population. Using comprehensive panels of single substitution
      analogs of specific ligands, we derived detailed binding motifs for
      DQA1*0501/DQB1*0301, DQA1*0401/DQB1*0402, and DQA1*0101/DQB1*0501 and more
      detailed motifs for DQA1*0501/DQB1*0201, DQA1*0301/DQB1*0302, and
      DQA1*0102/DQB1*0602, previously characterized on the basis of sets of eluted
      ligands and/or limited sets of substituted peptides. In contrast to what has
      previously been observed for DR and DP molecules, DQ motifs were generally less
      clearly defined in terms of chemical specificity and, strikingly, had little
      overlap with each other. However, testing a panel of peptides spanning a set of
      Phleum pratense Ags, and panels of known DQ epitopes, revealed a surprisingly
      significant and substantial overlap in the repertoire of peptides bound by these
      DQ molecules. Although the mechanism underlying these apparently contradictory
      findings is not clear, it likely reflects the peculiar mode of interaction
      between DQ (and not DR or DP) molecules and their peptide ligands. Because the DQ
      molecules studied are found in >85% of the general human population, these
      findings have important implications for epitope identification studies and
      monitoring of DQ-restricted immune responses.

PMID- 20810983
TI  - Discrete TCR repertoires and CDR3 features distinguish effector and Foxp3+
      regulatory T lymphocytes in myelin oligodendrocyte glycoprotein-induced
      experimental allergic encephalomyelitis.
AB  - Regulatory T lymphocytes (Tregs) expressing the Foxp3 transcription factor are
      critical modulators of autoimmunity. Foxp3(+) Tregs may develop in the thymus as
      a population distinct from conventional Foxp3(-) alphabeta T cells (Tconvs).
      Alternatively, plasticity in Foxp3 expression may allow for the interconversion
      of mature Tregs and Tconvs. We examined >160,000 TCR sequences from Foxp3(+) or
      Foxp3(-) populations in the spleens or CNS of wild-type mice with experimental
      allergic encephalomyelitis to determine their relatedness and identify
      distinguishing TCR features. Our results indicate that the CNS-infiltrating Tregs
      and Tconvs arise predominantly from distinct sources. The repertoires of CNS Treg
      or Tconv TCRs showed limited overlap with heterologous populations in both the
      CNS and the spleen, indicating that they are largely unrelated. Indeed, Treg and
      Tconv TCRs in the CNS were significantly less related than those populations in
      the spleen. In contrast, CNS Treg and Tconv repertoires strongly intersected
      those of the homologous cell type in the spleen. High-frequency sequences more
      likely to be disease associated showed similar results, and some public TCRs
      demonstrated Treg- or Tconv-specific motifs. Different charge characteristics and
      amino acid use preferences were identified in the CDR3beta of Tregs and Tconvs
      infiltrating the CNS, further indicating that their repertoires are qualitatively
      distinct. Therefore, discrete populations of Tregs and Tconvs that do not
      substantially interconvert respond during experimental allergic
      encephalomyelitis. Differences in sequence and physical characteristics
      distinguish Treg and Tconv TCRs and imply dissimilar Ag recognition properties.

PMID- 20810984
TI  - B cell subsets contribute to renal injury and renal protection after
      ischemia/reperfusion.
AB  - Ischemia/reperfusion (I/R) triggers a robust inflammatory response within the
      kidney. Numerous components of the immune system contribute to the resultant
      renal injury, including the complement system. We sought to identify whether
      natural Abs bind to the postischemic kidney and contribute to complement
      activation after I/R. We depleted peritoneal B cells in mice by hypotonic shock.
      Depletion of the peritoneal B cells prevented the deposition of IgM within the
      glomeruli after renal I/R and attenuated renal injury after I/R. We found that
      glomerular IgM activates the classical pathway of complement, but it does not
      cause substantial deposition of C3 within the kidney. Furthermore, mice deficient
      in classical pathway proteins were not protected from injury, indicating that
      glomerular IgM does not cause injury through activation of the classical pathway.
      We also subjected mice deficient in all mature B cells (MUMT mice) to renal I/R
      and found that they sustained worse renal injury than wild-type controls. Serum
      IL-10 levels were lower in the MUMT mice. Taken together, these results indicate
      that natural Ab produced by peritoneal B cells binds within the glomerulus after
      renal I/R and contributes to functional renal injury. However, nonperitoneal B
      cells attenuate renal injury after I/R, possibly through the production of IL-10.

PMID- 20810985
TI  - Latent membrane protein 1, the EBV-encoded oncogenic mimic of CD40, accelerates
      autoimmunity in B6.Sle1 mice.
AB  - EBV infection is associated with development of the autoimmune disease systemic
      lupus erythematosus (SLE), and EBV can reactivate during SLE flares. Latent
      membrane protein 1 (LMP1) is an EBV-encoded oncogenic mimic of CD40 that can be
      re-expressed in PBMCs during SLE flares, as >90% of humans are latently EBV
      infected. Whether LMP1 signaling exacerbates SLE is unknown. The phenotype of
      mice expressing a chimeric molecule with the mouse CD40 extracellular domain and
      the LMP1 intracellular signaling regions (mCD40-LMP1 transgenic [tg]) includes
      enhanced autoreactivity, yet these mice do not develop fatal autoimmune disease.
      We hypothesized that LMP1-mediated activation signals cooperate with and/or
      amplify events that predispose individuals to development of autoimmunity. To
      determine which aspects of autoimmunity may be exacerbated by LMP1, we bred mCD40
      LMP1tg mice to two lupus-prone strains, B6.Sle1 and B6.Sle3, and analyzed
      autoimmunity parameters. LMP1(+)Sle1(+/+) mice developed enlarged lymphoid organs
      containing increased frequencies of germinal center, B cells, CD86(+) B cells,
      and activated and memory T cells compared with non-tg littermates. Anti-histone
      Abs were elevated in serum of LMP1(+)Sle1(+/+) mice, and they had signs of kidney
      pathology. LMP1(+)Sle1(+/+) B cells produced increased IL-6 and upregulated CD86
      to a higher degree following CD40 stimulation in vitro, suggesting that the in
      vivo autoimmune exacerbation is B cell intrinsic. In contrast, the LMP1 transgene
      has no additional effects on autoimmunity on the B6.Sle3 background. These data
      indicate that LMP1-induced effects can cooperate with distinct subsets of host
      genes that predispose to autoimmunity and can thus be an exacerbating factor in
      autoimmune disease via multiple mechanisms.

PMID- 20810986
TI  - Surfactant protein-A inhibits mycoplasma-induced dendritic cell maturation
      through regulation of HMGB-1 cytokine activity.
AB  - During pulmonary infections, a careful balance between activation of protective
      host defense mechanisms and potentially injurious inflammatory processes must be
      maintained. Surfactant protein A (SP-A) is an immune modulator that increases
      pathogen uptake and clearance by phagocytes while minimizing lung inflammation by
      limiting dendritic cell (DC) and T cell activation. Recent publications have
      shown that SP-A binds to and is bacteriostatic for Mycoplasma pneumoniae in
      vitro. In vivo, SP-A aids in maintenance of airway homeostasis during M.
      pneumoniae pulmonary infection by preventing an overzealous proinflammatory
      response mediated by TNF-alpha. Although SP-A was shown to inhibit maturation of
      DCs in vitro, the consequence of DC/SP-A interactions in vivo has not been
      elucidated. In this article, we show that the absence of SP-A during M.
      pneumoniae infection leads to increased numbers of mature DCs in the lung and
      draining lymph nodes during the acute phase of infection and, consequently,
      increased numbers of activated T and B cells during the course of infection. The
      findings that glycyrrhizin, a specific inhibitor of extracellular high-mobility
      group box-1 (HMGB-1) abrogated this effect and that SP-A inhibits HMGB-1 release
      from immune cells suggest that SP-A inhibits M. pneumoniae-induced DC maturation
      by regulating HMGB-1 cytokine activity.

PMID- 20810987
TI  - T cell-induced mast cell activation: a role for microparticles released from
      activated T cells.
AB  - Close physical proximity between mast cells and T cells has been demonstrated in
      several T cell-mediated inflammatory processes. However, the way by which mast
      cells are activated in these T cell-mediated immune responses has not been fully
      elucidated. We previously identified and characterized a novel mast cell
      activation pathway initiated by physical contact with activated T cells and
      showed that this pathway is associated with degranulation and cytokine release.
      In this study, we provide evidence that mast cells may also be activated by
      microparticles released from activated T cells that are considered miniature
      versions of a cell. Microparticles were isolated from supernatants of activated T
      cells by Centricon filtration or by high-speed centrifugation and identified by
      electron microscopy, flow cytometry (Annexin stain), and expression of the
      integrin LFA-1. Stimulated T cells were found to generate microparticles that
      induce degranulation and cytokine (IL-8 and oncostatin M) release from human mast
      cells. Mast cell activation by T cell microparticles involved the MAPK signaling
      pathway. The results were similar when mast cells were stimulated by activated
      fixed T cells or by whole membranes of the latter. This suggests that
      microparticles carry mast cell-activating factors similar to cells from which
      they originate. By releasing microparticles, T cells might convey surface
      molecules similar to those involved in the activation of mast cells by cellular
      contact. By extension, microparticles might affect the activity of mast cells,
      which are usually not in direct contact with T cells at the inflammatory site.

PMID- 20810988
TI  - The class A scavenger receptor, macrophage receptor with collagenous structure,
      is the major phagocytic receptor for Clostridium sordellii expressed by human
      decidual macrophages.
AB  - Clostridium sordellii is an emerging pathogen associated with highly lethal
      female reproductive tract infections following childbirth, abortion, or cervical
      instrumentation. Gaps in our understanding of the pathogenesis of C. sordellii
      infections present major challenges to the development of better preventive and
      therapeutic strategies against this problem. We sought to determine the
      mechanisms whereby uterine decidual macrophages phagocytose this bacterium and
      tested the hypothesis that human decidual macrophages use class A scavenger
      receptors to internalize unopsonized C. sordellii. In vitro phagocytosis assays
      with human decidual macrophages incubated with pharmacological inhibitors of
      class A scavenger receptors (fucoidan, polyinosinic acid, and dextran sulfate)
      revealed a role for these receptors in C. sordellii phagocytosis. Soluble
      macrophage receptor with collagenous structure (MARCO) receptor prevented C.
      sordellii internalization, suggesting that MARCO is an important class A
      scavenger receptor in decidual macrophage phagocytosis of this microbe.
      Peritoneal macrophages from MARCO-deficient mice, but not wild-type or scavenger
      receptor AI/II-deficient mice, showed impaired C. sordellii phagocytosis. MARCO
      null mice were more susceptible to death from C. sordellii uterine infection than
      wild-type mice and exhibited impaired clearance of this bacterium from the
      infected uterus. Thus, MARCO is an important phagocytic receptor used by human
      and mouse macrophages to clear C. sordellii from the infected uterus.

PMID- 20810989
TI  - Lack of TNFR p55 results in heightened expression of IFN-gamma and IL-17 during
      the development of reactive arthritis.
AB  - Reactive arthritis (ReA) is a type of arthritis originating from certain
      gastrointestinal or genitourinary infections. In previous studies, we reported
      the development of progressive Yersinia enterocolitica-induced ReA in mice
      lacking TNFR p55; however, the mechanisms underlying this effect are still
      uncertain. In this study, we investigated the impact of TNFR p55 deficiency in
      modulating Ag-specific Th1 and Th17 responses during this arthritogenic process.
      We found more severe ReA in TNFRp55(-/-) mice compared with their wild-type (WT)
      counterparts. This effect was accompanied by increased levels of Yersinia LPS in
      the joints of knockout mice. Analysis of the local cytokine profile revealed
      greater amounts of IFN-gamma and IL-17 in arthritic joints of TNFRp55(-/-) mice
      compared with WT mice at day 21 postinfection. Moreover, altered IL-17 and IFN
      gamma production was observed in mesenteric and inguinal lymph nodes of Yersinia
      infected TNFRp55(-/-) mice, as well as in spleen cells obtained from infected
      mice and restimulated ex vivo with bacterial Ags. Increased levels of cytokine
      secretion were associated with a greater frequency of CD4(+)IL-17(+), CD4(+)IFN
      gamma(+), and IL-17(+)IFN-gamma(+) cells in TNFRp55(-/-) mice compared with WT
      mice. Remarkably, Ab-mediated blockade of IL-17 and/or IFN-gamma resulted in
      reduced joint histological scores in TNFRp55(-/-) mice. A mechanistic analysis
      revealed the involvement of p40, a common subunit of heterodimeric IL-12 and IL
      23, in the generation of augmented IFN-gamma and IL-17 production under TNFR p55
      deficiency. Taken together, these data indicate that, in the absence of TNFR p55
      signaling, Th1 and Th17 effector cells may act in concert to sustain the
      inflammatory response in bacterial-induced arthritogenic processes.

PMID- 20810990
TI  - p300-mediated acetylation stabilizes the Th-inducing POK factor.
AB  - The lineage-specifying factor Th-inducing POK (ThPOK) directs the intrathymic
      differentiation of CD4 T cells. Although the regulation of ThPOK at the
      transcription level has been extensively studied, specific posttranslational
      modifications regulating the activity of ThPOK have not been addressed. In this
      paper, we show that ThPOK is an unstable protein that is more readily degraded in
      CD8 T cells compared with CD4 T cells. Among the various proteins that bind
      ThPOK, acetyltransferase p300 specifically promotes the acetylation of ThPOK at
      K210, K216, and K339, outcompeting ubiquitination, thereby stabilizing the
      protein. In CD4 T cells, attenuation of p300-mediated acetylation promotes the
      degradation of ThPOK. In contrast, mutation of lysines 210, 216, and 339 to
      arginines stabilizes ThPOK and enhances its ability to suppress the expression of
      CD8 molecule and cytotoxic effectors in CD8 T cells. Our results reveal an
      essential role of p300-mediated acetylation in regulating the stability of ThPOK
      and suggest that such regulation may play a part in CD4/CD8 lineage
      differentiation.

PMID- 20810992
TI  - Cutting edge: MHC class II expression by pulmonary nonhematopoietic cells plays a
      critical role in controlling local inflammatory responses.
AB  - The interaction of CD4(+) T cells with MHC class II (MHCII)-expressing
      hematopoietic APCs plays a critical role in both the generation of protective
      immune responses and maintenance of tolerance in the lung. The functional
      significance of MHCII expression by nonhematopoietic stromal cells, however, has
      not been defined in vivo. Using a novel mouse model of orthotopic left lung
      transplantation, we demonstrate that selective elimination of MHCII expression on
      nonhematopoietic cells leads to an inflammatory response as a result of reduced
      peripheral generation of regulatory CD4(+) T cells. Absence of MHCII expression
      on nonhematopoietic cells also inhibits local growth of metastatic pulmonary
      tumor. These findings indicate that nonhematopoietic cells play a previously
      unrecognized role in downregulating inflammatory responses in nonlymphoid
      tissues.

PMID- 20810991
TI  - A crucial role for host APCs in the induction of donor CD4+CD25+ regulatory T
      cell-mediated suppression of experimental graft-versus-host disease.
AB  - Allogeneic bone marrow transplantation is an effective treatment for a number of
      malignant and nonmalignant diseases (Applebaum. 2001. Nature. 411: 385-389 and
      Copelan. 2006. N Engl J Med. 354: 1813-1826). However, the application of this
      therapeutic modality has been impeded by a number of confounding side effects,
      the most frequent and severe of which is the development of graft-versus-host
      disease (GVHD) (Copelan. 2006. N Engl J Med. 354: 1813-1826 and Blazar and
      Murphy. 2005. Philos Trans R Soc Lond B Biol Sci. 360: 1747-1767). Alloreactive
      donor T cells are critical for causing GVHD (Fowler. 2006. Crit Rev Oncol
      Hematol. 57: 225-244 and Ferrara and Reddy. 2006. Semin Hematol. 43: 3-10),
      whereas recent data demonstrated a significant role for the naturally occurring
      thymic-derived donor CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) (Bluestone
      and Abbas. 2003. Nat Rev Immunol. 3: 253-257 and Shevach. 2006. Immunity. 25: 195
      201) in suppressing experimental GVHD after bone marrow transplantation (Blazar
      and Taylor. 2005. Biol Blood Marrow Transpl. 11: 46-49 and Joffe and van
      Meerwijk. 2006. Semin Immunol. 18: 128-135) . Host APCs are required for
      induction of GVHD by the conventional donor T cells. However, it is not known
      whether they are also obligatory for donor Treg-mediated suppression of GVHD.
      Using multiple clinically relevant MHC-matched and -mismatched murine models of
      GVHD, we investigated the role of host APCs in the suppression of GVHD by donor
      Tregs. We found that alloantigen expression by the host APCs is necessary and
      sufficient for induction of GVHD protection by donor Tregs. This requirement was
      independent of their effect on the maintenance of Treg numbers and the production
      of IL-10 or IDO by the host APCs.

PMID- 20810993
TI  - An alternative role of C1q in cell migration and tissue remodeling: contribution
      to trophoblast invasion and placental development.
AB  - Fetal trophoblast cells invading the decidua in the early phase of pregnancy
      establish complex interaction with the maternal extracellular matrix. We
      discovered that C1q was widely distributed in human decidual stroma in the
      absence of C4 and C3 and was actively synthesized by migrating extravillous
      trophoblasts. The cells expressed the messages for the three chains of C1q and
      secreted this complement component that interacted with the proteins of the
      decidual extracellular matrix. Solid phase-bound C1q promoted trophoblast
      adhesion and migration, and cell binding to C1q resulted in activation of ERK1/2
      MAPKs. Ab inhibition experiments showed that the receptors for the globular head
      of C1q/p33 and alpha(4)beta(1) integrin were both involved in this process and
      were colocalized on the cell surface following binding of C1q to trophoblasts. We
      also found that C1q(-/-) mice manifested increased frequency of fetal resorption,
      reduced fetal weight, and smaller litter sizes compared with wild-type mice. C1q
      deficiency was associated with impaired labyrinth development and decidual vessel
      remodeling. Collectively, these data suggest that C1q plays an important role in
      promoting trophoblast invasion of decidua and that defective local production of
      C1q may be involved in pregnancy disorders, such as pre-eclampsia, characterized
      by poor trophoblast invasion.

PMID- 20810994
TI  - Inhibition of hepatitis C virus replication by IFN-mediated ISGylation of HCV
      NS5A.
AB  - ISG15 is a ubiquitin-like molecule whose expression is induced by type I IFN (IFN
      alpha/beta) or in response to virus or bacterial infection. ISG15 or conjugation
      of ISG15 to target proteins was reported to play critical roles in the regulation
      of antiviral responses. IFN restricts replication of hepatitis C virus (HCV).
      However, molecular mechanism of IFN-alpha/beta that inhibits HCV replication is
      not clear yet. In the current study, we demonstrated that replication of HCV was
      inhibited by overexpression of ISG15 and ISG15-conjugation enzymes in the HCV
      subgenomic replicon cells. Among various nonstructural proteins of HCV, NS5A was
      identified as the substrate for ISGylation. Furthermore, protein stability of
      NS5A was decreased by overexpression of ISG15 or ISG15-conjugating enzymes. The
      inhibitory effect of ISG15 or ISGylation on NS5A was efficiently blocked by
      substitution of lysine at 379 residue to arginine within the C-terminal region,
      suggesting that ISGylation directly controls protein stability of NS5A. Finally,
      the inhibitory effect of IFN-alpha/beta on HCV replication was further enhanced
      by ISGylation, suggesting ISG15 as a therapeutic tool for combined therapy with
      IFN against HCV.

PMID- 20810995
TI  - A Notch ligand, Delta-like 1 functions as an adhesion molecule for mast cells.
AB  - Mast cells (MCs) accumulate in chronic inflammatory sites; however, it is not
      clear which adhesion molecules are involved in this process. Recently, the
      expression of Notch ligands was reported to be upregulated in inflammatory sites.
      Although Notch receptors are known as signaling molecules that can activate
      integrins, their contributions to the adhesion of MCs have not been studied. In
      this study, we demonstrated that mouse MCs efficiently adhered to stromal cells
      forced to express a Notch ligand, Delta-like 1 (Dll1). Surprisingly, the adhesion
      was a consequence of direct cell-cell interaction between MCs and Dll1-expressing
      stromal cells rather than activation of downstream effectors of Notch receptor(s)
      Dll1. The adhesion of MCs to Dll1-expressing stromal cells remained even when the
      cell metabolism was arrested. The recognition was blocked only by inhibition of
      Notch receptor(s)-Dll1 interaction by addition of soluble DLL1, or mAbs against
      Dll1 or Notch2. Taken together, these results indicate that Notch receptor(s) and
      Dll1 directly promote the adhesion of MCs to stromal cells by acting as adhesion
      molecules. This appreciation that Notch receptor-ligand interactions have an
      adhesion function will provide an important clue to molecular basis of
      accumulation of MCs to inflammatory sites.

PMID- 20810996
TI  - Albuminuria and the risk of incident stroke and stroke types in older adults.
AB  - BACKGROUND: The kidney biomarker that best reflects risk of stroke is unknown. We
      sought to evaluate the association of stroke with 3 kidney biomarkers:
      albuminuria, cystatin C, and glomerular filtration rate. METHODS: These 3
      biomarkers were determined in 3,287 participants without history of stroke from
      the Cardiovascular Health Study, a longitudinal cohort study of men and women age
      65 years and older from 4 US communities. The biomarkers were albuminuria
      ascertained using urinary albumin-to-creatinine ratio (UACR) from morning spot
      urine, creatinine-based estimated glomerular filtration rate (eGFR), and cystatin
      C. Outcomes were incident stroke (any, ischemic, or hemorrhagic) during follow-up
      between 1996 and 2006. RESULTS: A total of 390 participants had an incident
      stroke: 81% ischemic, 12% hemorrhagic, and 7% unclassified. In adjusted Cox
      regression models, UACR was more strongly related to any stroke, ischemic stroke,
      and hemorrhagic stroke than eGFR and cystatin C. The hazard ratio (HR) of any
      stroke comparing the top to bottom quintile of UACR was 2.10 (95% confidence
      interval [CI] 1.47-3.00), while HR for eGFR was 1.29 (95% CI 0.91-1.84) and for
      cystatin C was 1.22 (95% CI 0.85-1.74). When considering clinically relevant
      categories, elevated UACR was associated with increased hazard of any stroke and
      ischemic stroke regardless of eGFR or cystatin C categories. CONCLUSIONS: UACR
      was the kidney biomarker most strongly associated with risk of incident stroke.
      Results in this elderly cohort may not be applicable to younger populations.
      These findings suggest that measures of glomerular filtration and permeability
      have differential effects on stroke risk.

PMID- 20810997
TI  - Associations between retinal nerve fiber layer abnormalities and optic nerve
      examination.
AB  - OBJECTIVE: Retinal nerve fiber layer (RNFL) abnormalities detected by optical
      coherence tomography (OCT) are useful markers for axonal loss and visual
      dysfunction in multiple sclerosis (MS), but their role in routine clinical
      management is not well-studied. METHODS: Clinical and OCT examinations were
      performed on 240 patients attending a neurology clinic. Using OCT 5th percentile
      to define abnormal RNFL thickness, we compared eyes classified by neurologists as
      having optic atrophy to RNFL thickness, and afferent pupillary defect (APD) to
      RNFL thickness ratios of eye pairs. RESULTS: Mean RNFL thickness was less in eyes
      classified by neurologists as having optic atrophy (79.4 +/- 21 MUm; n=63) vs
      those without (97.0 +/- 15 MUm; n=417; p < 0.001, t test) and in eyes with an APD
      (84.1 +/- 16 MUm; n=44) than without an APD (95.8 +/- 17 MUm; n=436; p < 0.001).
      Physicians' diagnostic accuracy for detecting pallor in eyes with an abnormal
      RNFL thickness was 79% (sensitivity=0.56; specificity=0.82). Accuracy for
      detecting a RAPD in patients with mean RNFL ratio (affected eye to unaffected
      eye) <0.90 was 73% (sensitivity=0.30; specificity=0.86). Ability to detect visual
      pathway injury via assessment of atrophy and APD differed between neurologists.
      CONCLUSIONS: OCT reveals RNFL abnormality in many patients in whom eyes are not
      classified by neurologic examiners as having optic atrophy. Further study is
      needed to define the role of OCT measures in the context of examinations for
      optic atrophy and APD by neuroophthalmologists. OCT-measured RNFL thickness is
      likely to have an important future role in the clinical setting.

PMID- 20810998
TI  - Effects of a central cholinesterase inhibitor on reducing falls in Parkinson
      disease.
AB  - OBJECTIVE: To investigate if a central cholinesterase inhibitor will reduce
      falling frequency in subjects with Parkinson disease (PD) with advanced postural
      instability. BACKGROUND: Falling due to postural instability is a significant
      problem in advancing PD, and is minimally impacted by dopaminergic therapy.
      Anticholinergic medications increase falling in the elderly. Further, CNS
      cholinergic neuron loss occurs in PD. We hypothesized that acetylcholine
      augmentation may reduce frequent falling in subjects with PD. METHODS: We
      enrolled 23 subjects with PD who reported falling or nearly falling more than 2
      times per week. In a randomized, placebo-controlled, crossover design, subjects
      were given 6 weeks of donepezil or placebo with a 3-week washout between phases.
      The primary outcomes were daily falls and near falls reported on postcards.
      Secondary outcomes included scores on the Activities of Balance Confidence Scale,
      Berg Balance Scale, Clinical Global Impression of Change, Folstein Mini-Mental
      State Examination, and the motor section of the Unified Parkinson's Disease
      Rating Scale. RESULTS: Fall frequency per day on placebo was 0.25 +/- 0.08 (SEM)
      compared with 0.13 +/- 0.03 on donepezil (p < 0.05). The frequency of near falls
      was not significantly different between phases. The secondary outcomes did not
      differ; however, there was a trend to improvement on the subject-completed Global
      Impression of Change scale. CONCLUSIONS: Subjects with PD fell approximately half
      as often during the 6 weeks on donepezil than on placebo. Larger trials of
      cholinergic augmentation are warranted in subjects with PD with frequent falls.
      CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that donepezil
      (maximum 10 mg per day) significantly reduced the number of falls in patients
      with PD (0.13 falls/day, SEM = 0.03) than when taking placebo (0.25 falls/day,
      SEM = 0.08, p = 0.049).

PMID- 20810999
TI  - Incidence and subtypes of early-onset dementia in a geographically defined
      general population.
AB  - OBJECTIVE: To estimate the incidence of early-onset dementia (EOD) and to compare
      the clinical characteristics of EOD vs late-onset dementia (LOD) in a
      geographically defined area. METHODS: We used data from the Registry of Dementia
      of Girona (ReDeGi), an epidemiologic surveillance system of dementia. The ReDeGi
      is a standardized clinical registry of new dementia cases diagnosed in the 7
      hospitals of the Health Region of Girona (Catalonia, Spain), which encompasses an
      area of 5,517 km(2) and 690,207 inhabitants. EOD cases were defined as those
      patients residing in the target area at the time of diagnosis who were diagnosed
      with dementia with an age at onset of symptoms before 65 years. RESULTS: The
      ReDeGi registered 2,083 patients between January 1, 2007, and December 31, 2009
      (6.9% EOD). The incidence rate of EOD for the age range 30-64 was 13.4 cases per
      100,000 person-years (95% confidence interval 11.3-15.8). Alzheimer disease was
      the most frequent cause of EOD (42.4%), followed by secondary dementia (18.1%),
      vascular dementia (13.8%), and frontotemporal dementia (9.7%). EOD cases at the
      time of diagnosis were less impaired on the Mini-Mental State Examination and had
      a greater score on the Blessed Dementia Rating Scale behavior subscale than LOD
      cases. The frequency of a personal history of depression was higher in EOD cases.
      CONCLUSIONS: The incidence of EOD was less than 6 cases per 100,000 person-years
      in the age group 30-49 years; in the age group 50-64 years, the incidence rate
      was 3-fold higher and doubled with each 5-year increase.

PMID- 20811000
TI  - Nonsteroidal anti-inflammatory drugs are associated with increased neuritic
      plaques.
AB  - OBJECTIVES: Observational and experimental studies suggest that nonsteroidal anti
      inflammatory drugs (NSAIDs) may protect against Alzheimer disease (AD); however,
      clinical trials and other observational studies, including the Adult Changes in
      Thought (ACT) study, show no protection or promotion of AD. The objective of this
      study is to determine the relationship between common dementia-associated
      pathologies and mid- to late-life NSAID exposure. METHODS: We examined the
      association of mid- to late-life NSAID use with neuropathologic findings on 257
      autopsies from ACT, a population-based study of brain aging and incident
      dementia. Cumulative standard daily doses (SDD) of nonselective NSAIDs were
      determined from >=10 years of computerized pharmacy dispensing data. Analyses
      were adjusted for selection bias to broaden generalizability of results to 3,026
      eligible participants in the ACT cohort. Seven pathologic indices were evaluated:
      intermediate or frequent score for neuritic plaques, Braak stages V or VI for
      neurofibrillary tangles, >2 cerebral microinfarcts, the presence of any
      neocortical Lewy bodies, any macroscopic infarcts, any amyloid angiopathy, and
      moderate or severe atherosclerosis. RESULTS: Of the neuropathologic indices
      evaluated, only neuritic plaque score was significantly increased in participants
      with greater use of nonselective NSAIDs (p = 0.065), specifically in those with
      high levels of cumulative use: 1,000-2,000 SDD (adjusted relative risk [RR] 2.16,
      95% confidence interval [CI] 1.02-4.25, compared to light/nonuse [<60 SDD]) and
      >2,000 SDD (adjusted RR 2.37, 95% CI 1.24-4.67). CONCLUSIONS: Increased neuritic
      plaque accumulation may explain the association between heavy use of nonselective
      NSAIDs and increased risk of dementia among ACT participants.

PMID- 20811001
TI  - Cognitive activity and the cognitive morbidity of Alzheimer disease.
AB  - OBJECTIVE: To test the hypothesis that frequent cognitive activity predicts
      slower cognitive decline before dementia onset in Alzheimer disease (AD) and
      faster decline thereafter. METHODS: As part of a longitudinal cohort study, older
      residents of a geographically defined population were assessed at 3-year
      intervals with brief cognitive performance tests from which a composite measure
      of global cognition was derived. After each wave of testing, a subset was sampled
      for clinical evaluation. The present analyses are based on 1,157 participants.
      They were free of dementia at study enrollment at which time they rated frequency
      of participation in common cognitively stimulating activities from which a
      previously validated summary measure was derived. They were sampled for clinical
      evaluation a mean of 5.6 years after enrollment and subsequently followed a mean
      of 5.7 years with brief cognitive performance testing at 3-year intervals.
      RESULTS: On clinical evaluation, 614 people had no cognitive impairment, 395 had
      mild cognitive impairment, and 148 had AD. During follow-up, the annual rate of
      global cognitive decline in persons without cognitive impairment was reduced by
      52% (estimate = 0.029, SE = 0.010, p = 0.003) for each additional point on the
      cognitive activity scale. In the mild cognitive impairment group, cognitive
      decline rate was unrelated to cognitive activity (estimate = -0.019, SE = 0.018,
      p = 0.300). In AD, the mean rate of decline per year increased by 42% (estimate =
      0.075, SE = 0.021, p < 0.001) for each point on the cognitive activity scale.
      CONCLUSION: Mentally stimulating activity in old age appears to compress the
      cognitive morbidity associated with AD by slowing cognitive decline before
      dementia onset and hastening it thereafter.

PMID- 20811002
TI  - Effect of multikinase inhibitors on caspase-independent cell death and DNA damage
      in HER2-overexpressing breast cancer cells.
AB  - BACKGROUND: The receptor tyrosine kinase, HER2, is overexpressed in approximately
      25% of patients with breast cancer and is implicated in the aggressiveness of
      cancer. Targeting of HER2 signaling with trastuzumab, a monoclonal antibody that
      inhibits HER2 activity, has demonstrated clinical benefits. METHODS: We
      investigated whether the antitumor activity of trastuzumab can be potentiated by
      dasatinib, a small-molecule tyrosine kinase inhibitor, on breast cancer cell
      lines that overexpress HER2 (BT474 and SKBR3) or have normal HER2 expression
      (MCF7 and T47D). Functional, biochemical, and gene expression microarray studies
      were performed to test the effect of trastuzumab, dasatinib, or a combination of
      trastuzumab and dasatinib on cell proliferation; HER activation; cell cycle; DNA
      damage; and apoptosis. The effect of drugs on mice (n = 6 per group) bearing
      xenograft tumors originating from HER2-overexpressing BT474 cells was assessed,
      and tumors were evaluated for an effect on volume, HER signaling, and DNA damage.
      All statistical tests were two-sided. RESULTS: Trastuzumab and dasatinib
      combination showed a synergistic effect on the proliferation of HER2
      overexpressing breast cancer cells (combination index = 0.44, 95% confidence
      interval = 0.30 to 0.58). The drug combination also induced a stronger inhibitory
      effect on HER2 activation than the individual drugs, decreased the level of
      proteins involved in DNA damage response, induced DNA double-strand breaks, cell
      cycle arrest, and caspase-independent apoptosis. Mice (n = 6 per group) bearing
      xenograft tumors originating from HER2-overexpressing BT474 cells showed
      statistically significantly reduced tumor volume on day 28 when treated with the
      drug combination (control vs trastuzumab and dasatinib combination; mean volume =
      2.6 vs 0.5 cm(3), difference = 2.1 cm(3), 95% confidence interval = 0.76 to 3.51
      cm(3), P = .01) and total regression of tumors by day 36 with no later relapse.
      CONCLUSIONS: Results showed that HER2 and dasatinib-sensitive tyrosine kinases
      act in a synergistic manner to safeguard the breast cancer cells from DNA damage.
      The therapeutic targeting of multikinase inhibition opens new avenues for the
      treatment of HER2-positive breast cancer patients.

PMID- 20811003
TI  - Re: Impact of human papillomavirus (HPV)-6/11/16/18 vaccine on all HPV-associated
      genital diseases in young women.

PMID- 20811004
TI  - Secretoneurin is a potential paracrine factor from lactotrophs stimulating
      gonadotropin release in the goldfish pituitary.
AB  - Secretoneurin (SN) is a functional neuropeptide derived from the evolutionarily
      conserved part of precursor protein secretogranin II (SgII). In the time course
      study, SN (10 nM) stimulates luteinizing hormone (LH) production and secretion
      after 6 h of static incubation of goldfish pituitary cells. Due to the existence
      of SN-immunoreactivity (SN-IR) in goldfish lactotrophs, endogenous SN might exert
      a paracrine effect on LH in the pituitary. In an in vitro immunoneutralization
      experiment, coincubation with anti-SN antiserum reduces the stimulatory effect of
      salmon gonadotropin-releasing hormone (sGnRH) on LH release by 64%. Using Western
      blot analysis, we demonstrate that sGnRH significantly increases the expression
      of the major SgII-derived peptide (~57 kDa, with SN-IR) and prolactin (PRL) after
      12 h in the static culture of goldfish pituitary cells. Furthermore, there exists
      a significant correlation between the levels of these two proteins (R = 0.76, P =
      0.004). Another ~30 kDa SgII-derived peptide containing SN is only observed in
      sGnRH-treated pituitary cells. Consistent with the Western blot analysis results,
      real-time RT-PCR analysis shows that a 12-h treatment with sGnRH induced 1.6- and
      1.7-fold increments in SgII and PRL mRNA levels, respectively. SgII gene
      expression was also associated with PRL gene expression (R = 0.66; P = 0.02). PRL
      cells loaded with the calcium-sensitive dye, fura 2/AM, respond to sGnRH
      treatment with increases in intracellular Ca(2+) concentration level, suggesting
      a potential mechanism of GnRH on PRL cells and thus SgII processing and SN
      secretion. Taken together, endogenous lactotroph-generated SN, under the control
      of hypothalamic GnRH, exerts a paracrine action on neighboring gonadotrophs to
      stimulate LH release.

PMID- 20811005
TI  - Rostral ventrolateral medullary but not medullary lateral tegmental field neurons
      mediate sympatho-sympathetic reflexes in cats.
AB  - This study was designed to build on past work from this laboratory by testing the
      hypothesis that medullary lateral tegmental field (LTF) neurons play a critical
      role in mediating sympathoexcitatory responses to activation of sympathetic
      afferent fibers. We studied the effects of microinjection of N-methyl-d-aspartate
      (NMDA) or non-NMDA receptor antagonists or muscimol bilaterally into the LTF on
      the area under the curve of the computer-averaged sympathoexcitatory potential in
      the right inferior cardiac nerve elicited by short trains of stimuli applied to
      afferent fibers in the left inferior cardiac or left splanchnic nerve (CN, SN) of
      baroreceptor-denervated and vagotomized cats anesthetized with a mixture of
      diallylbarbiturate and urethane. In contrast to our hypothesis,
      sympathoexcitatory responses to stimulation of CN (n = 5-7) or SN (n = 4-7)
      afferent fibers were not significantly affected by these procedures. We then
      determined whether the rostral and caudal ventrolateral medulla (RVLM, CVLM) and
      nucleus tractus solitarius (NTS) were involved in mediating these reflexes.
      Blockade of non-NMDA, but not NMDA, receptors in the RVLM significantly reduced
      the area under the curve of the sympathoexcitatory responses to electrical
      stimulation of either CN (P = 0.0110; n = 6) or SN (P = 0.0131; n = 5) afferent
      fibers. Neither blockade of excitatory amino acid receptors nor chemical
      inactivation of CVLM or NTS significantly affected the responses. These data show
      that activation of non-NMDA receptors in the RVLM is a critical step in mediating
      the sympatho-sympathetic reflex.

PMID- 20811006
TI  - Neonatal stress and attenuation of the hypercapnic ventilatory response in adult
      male rats: the role of carotid chemoreceptors and baroreceptors.
AB  - Neonatal maternal separation (NMS) is a form of stress that disrupts respiratory
      control development. Awake adult male rats previously subjected to NMS show a
      ventilatory response to hypercapnia (HCVR; Fi(CO(2)) = 0.05) 47% lower than
      controls; however, the underlying mechanisms are unknown. To address this issue,
      we first tested the hypothesis that carotid bodies contribute to NMS-related
      attenuation of the HCVR by using carotid sinus nerve section or Fi(O(2))
      manipulation to maintain Pa(O(2)) constant (iso-oxic) during hypercapnic
      hyperpnea. We then determined whether NMS-related augmentation of baroreflex
      sensitivity contributes to the reduced HCVR in NMS rats. Nitroprusside and
      phenylephrine injections were used to manipulate arterial blood pressure in both
      groups of rats. Pups subjected to NMS were separated from their mother 3 h/day
      from postnatal days 3 to 12. Control rats were undisturbed. At adulthood, rats
      were anesthetized [urethane (1g/kg) + isoflurane (0.5%)], and diaphragmatic
      electromyogram (dEMG) was measured under baseline and hypercapnic conditions
      (Pa(CO(2)): 10 Torr above baseline). The relative minute activity response to
      hypercapnia of anesthetized NMS rats was 34% lower than controls. Maintaining
      Pa(O(2)) constant during hypercapnia reversed this phenotype; the HCVR of NMS
      rats was 45% greater than controls. Although the decrease in breathing frequency
      during baroreflex activation was greater in NMS rats, the change observed within
      the range of pressure change observed during hypercapnia was minimal. We conclude
      that NMS-related changes in carotid body sensitivity to chemical stimuli and/or
      its central integration is a key mechanism in the attenuation of HCVR by NMS.

PMID- 20811008
TI  - The water-absorption region of ventral skin of several semiterrestrial and
      aquatic anuran amphibians identified by aquaporins.
AB  - Regions of specialization for water absorption across the skin of Bufonid and
      Ranid anurans were identified by immunohistochemistry and Western blot analysis,
      using antibodies raised against arginine vasotocin (AVT)-stimulated aquaporins
      (AQPs) that are specific to absorbing regions of Hyla japonica. In Bufo marinus,
      labeling for Hyla urinary bladder-type AQP (AQP-h2), which is also localized in
      the urinary bladder, occurred in the ventral surface of the hindlimb, pelvic, and
      pectoral regions. AQP-h2 was not detected in any skin regions of Rana
      catesbeiana, Rana japonica, or Rana nigromaculata. Hyla ventral skin-type AQP
      (AQP-h3), which is found in the ventral skin but not the bladder of H. japonica,
      was localized in the hindlimb, pelvic, and pectoral skins of Bufo marinus, in
      addition to AQP-h2. AQP-h3 was also localized in ventral skin of the hindlimb of
      all three Rana species and also in the pelvic region of R. catesbiana. Messenger
      RNA for AQP-x3, a homolog of AQP-h3, could be identified by RT-PCR from the
      hindlimb, pectoral, and pelvic regions of the ventral skin of Xenopus laevis,
      although AVT had no effect on water permeability. In contrast, 10(-8) M AVT
      stimulated water permeability and translocation of AQP-h2 and AQP-h3 into the
      apical membrane of epithelial cells in regions of the skin of species where they
      had been localized by immunohistochemistry and Western blot analysis. Finally,
      water permeability of the hindlimb skin of B. marinus and all the Rana species
      was stimulated by hydrins 1 and 2 to a similar level as seen for AVT. The present
      data demonstrate species differences in the occurrence, distribution, and
      regulation of AQPs in regions of skin specialized for rapid water absorption that
      can be associated with habitat and also phylogeny.

PMID- 20811007
TI  - Intracellular energetics and critical PO2 in resting ischemic human skeletal
      muscle in vivo.
AB  - During ischemia and some types of muscular contractions, oxygen tension (Po(2))
      declines to the point that mitochondrial ATP synthesis becomes limited by oxygen
      availability. Although this critical Po(2) has been determined in animal tissue
      in vitro and in situ, there remains controversy concerning potential disparities
      between values measured in vivo and ex vivo. To address this issue, we used
      concurrent heteronuclear magnetic resonance spectroscopy (MRS) to determine the
      critical intracellular Po(2) in resting human skeletal muscle in vivo. We
      interleaved measurements of deoxymyoglobin using (1)H-MRS with measures of high
      energy phosphates and pH using (31)P-MRS, during 15 min of ischemia in the
      tibialis anterior muscles of 6 young men. ATP production and intramyocellular
      Po(2) were quantified throughout ischemia. Critical Po(2), determined as the
      Po(2) corresponding to the point where PCr begins to decline (PCr(ip)) in resting
      muscle during ischemia, was 0.35 +/- 0.20 Torr, means +/- SD. This in vivo value
      is consistent with reported values ex vivo and does not support the notion that
      critical Po(2) in resting muscle is higher when measured in vivo. Furthermore, we
      observed a 4.5-fold range of critical Po(2) values among the individuals studied.
      Regression analyses revealed that time to PCr(ip) was associated with critical
      Po(2) and the rate of myoglobin desaturation (r = 0.83, P = 0.04) but not the
      rate of ATP consumption during ischemia. The apparent dissociation between ATP
      demand and myoglobin deoxygenation during ischemia suggests that some degree of
      uncoupling between intracellular energetics and oxygenation is a potentially
      important factor that influences critical Po(2) in vivo.

PMID- 20811009
TI  - Nitric oxide generation in children with malaria and the NOS2G-954C promoter
      polymorphism.
AB  - Previous epidemiological studies have demonstrated a protective association
      between the NOS2G-954C (NOS2(Lambarene)) polymorphism in inducible nitric oxide
      synthase and severe malaria. The polymorphism is commoner in children with
      uncomplicated compared with severe malaria. We now show that the likely mechanism
      for such protection is increased flux of nitrogen from arginine to nitric oxide
      (NO) during episodes of malaria. Forty-seven boys with uncomplicated malaria
      received an infusion of (15)N-arginine to measure directly whole body in vivo NO
      production. The NOS2G-954C genotype previously associated with reduced risk of
      severe malaria in Gabon was also assessed. Evaluable data were obtained from 40
      boys, of whom 6 were NOS2G-954C heterozygotes. Heterozygotes had higher urinary
      (15)N nitrate enrichments, 2.3 +/- 0.6 vs. 1.4 +/- 0.5 atoms percent excess (P =
      0.001) and higher ratios of (15)N between urine nitrate and plasma arginine (87
      +/- 11 vs. 57 +/- 18%, P = 0.001) consistent with accelerated NO production. We
      also derived total NO production rates, combining data with total urine
      production rate and nitrate concentration; these showed no difference by genotype
      (0.62 +/- 0.36, n = 6 vs. 0.83 +/- 0.50 MUmol/kg.h, n = 16; P = 0.36), but data
      were confounded by very high variability in measurements of urine output and
      nitrate concentrations. This study supports the idea that NOS2 genotype protects
      against severe malaria by increasing NO production during episodes of
      uncomplicated malaria.

PMID- 20811010
TI  - Myristate is selectively incorporated into surfactant and decreases
      dipalmitoylphosphatidylcholine without functional impairment.
AB  - Lung surfactant mainly comprises phosphatidylcholines (PC), together with
      phosphatidylglycerols and surfactant proteins SP-A to SP-D. Dipalmitoyl-PC
      (PC16:0/16:0), palmitoylmyristoyl-PC (PC16:0/14:0), and palmitoylpalmitoleoyl-PC
      (PC16:0/16:1) together comprise 75-80% of surfactant PC. During alveolarization,
      which occurs postnatally in the rat, PC16:0/14:0 reversibly increases at the
      expense of PC16:0/16:0. As lipoproteins modify surfactant metabolism, we
      postulated an extrapulmonary origin of PC16:0/14:0 enrichment in surfactant. We,
      therefore, fed rats (d19-26) with trilaurin (C12:0(3)), trimyristin (C14:0(3)),
      tripalmitin (C16:0(3)), triolein (C18:1(3)) or trilinolein (C18:2(3)) vs.
      carbohydrate diet to assess their effects on surfactant PC composition and
      surface tension function using a captive bubble surfactometer. Metabolism was
      assessed with deuterated C12:0 (omega-d(3)-C12:0) and omega-d(3)-C14:0. C14:0(3)
      increased PC16:0/14:0 in surfactant from 12 +/- 1 to 45 +/- 3% and decreased
      PC16:0/16:0 from 47 +/- 1 to 29 +/- 2%, with no impairment of surface tension
      function. Combined phospholipase A(2) assay and mass spectrometry revealed that
      50% of the PC16:0/14:0 peak comprised its isomer 1-myristoyl-2-palmitoyl-PC
      (PC14:0/16:0). While C12:0(3) was excluded from incorporation into PC, it
      increased PC16:0/14:0 as well. C16:0(3), C18:1(3), and C18:2(3) had no
      significant effect on PC16:0/16:0 or PC16:0/14:0. d(3)-C14:0 was enriched in lung
      PC, either via direct supply or via d(3)-C12:0 elongation. Enrichment of d(3)
      C14:0 in surfactant PC contrasted its rapid turnover in plasma and liver PC,
      where its elongation product d(3)-C16:0 surmounted d(3)-C14:0. In summary, high
      surfactant PC16:0/14:0 during lung development correlates with C14:0 and C12:0
      supply via specific C14:0 enrichment into lung PC. Surfactant that is high in
      PC16:0/14:0 but low in PC16:0/16:0 is compatible with normal respiration and
      surfactant function in vitro.

PMID- 20811013
TI  - Developmental changes in expression of genes involved in regulation of apoptosis
      in the bovine preimplantation embryo.
AB  - The early bovine preimplantation embryo is resistant to proapoptotic signals
      until around the 8- to 16-cell stage. We hypothesized that 2-cell embryos have
      higher amounts of antiapoptotic proteins and lower amounts of proapoptotic
      proteins when compared to embryos >=16 cells. Steady-state concentrations of mRNA
      for the antiapoptotic genes BCL2 and HSPA1A were higher for MII oocytes, 2-cell
      embryos, and 2-cell embryos treated with alpha-amanitin as compared to >=16-cell
      embryos. Steady-state concentrations of mRNA for the proapoptotic gene BAD
      increased in embryos >=16 cells. There was no significant effect of stage of
      development on steady-state mRNA concentrations of BCL2L1, DFFA, or BAX. Using
      immunohistochemistry, it was found that BCL2 was present in greater relative
      concentrations for 2-cell embryos than for embryos >=16 cells. These results were
      confirmed by Western blotting. Relative amounts of immunoreactive BAX detected by
      immunofluorescence were lower for 2-cell embryos than for embryos >=16 cells.
      Using Western blotting, a high molecular weight (46 kDa) form of BAX was highest
      in >=16-cell embryos, intermediate in 2-cell embryos, and lowest in MII oocytes.
      There were no effects of stage of development on relative amounts of
      immunoreactive BCL2L1, HSPA1A, or BAD, as determined by immunofluorescence.
      Treatment of embryos with alpha-amanitin from Day 0 to Day 5 or Day 4 to Day 5
      after insemination reduced activation of group II caspases and terminal
      deoxynucleotidyl transferase dUTP nick end labeling after treatment with the
      proapoptotic signal C(2) ceramide at Day 5 after fertilization. Thus,
      transcription of BAX or other proteins is required for acquisition of the
      capacity for apoptosis. Results support the idea that changes in amounts of BCL2
      family members are important for the inhibition of apoptosis in the 2-cell embryo
      and in the establishment of the capacity for apoptosis later in development.

PMID- 20811014
TI  - Postejaculatory increase of prostatic triiodothyronine (T3) depends on
      sympathetic innervation in the rat.
AB  - Thyronines are essential for the development of the male reproductive system,
      including the prostate gland. Metabolically active 3,5,3' triiodothyronine (T(3))
      is generated mainly by the extrathyroidal, enzymatic 5'deiodination of the
      prohormone thyroxine (T(4)), which is catalyzed by deiodinases type 1 (D1) and
      type 2 (D2). Prostate D1 activity is highly expressed during puberty and declines
      with age, but continuous, long-term sexual activity prevents this reduction. The
      aims of this study were to characterize the changes in prostatic D1 activity in
      response to consecutive ejaculations and to determine whether sympathetic input
      participates in the local T(3) generation (D1 activity). D1 activity was analyzed
      in prostates of sexually experienced, 4-mo-old male rats after one to five
      ejaculations. D1 activity, T(3) concentrations, and the T(3)-dependent gene
      ornithine decarboxylase (Odc) were measured after the fourth ejaculation in
      prostates of intact, sham, and sympathectomized (Smpx, hypogastric nerve) rats.
      D1 activity was evaluated by the radio-iodine-release method; T(3) was measured
      by radioimmunoassay and Odc expression by real-time PCR. Data showed a gradual
      increase of prostate D1 activity in response to consecutive ejaculations. The
      highest activity was found after the fourth ejaculation, and it decreased after
      the fifth. The increase of prostate D1 activity after ejaculation was blocked in
      Smpx males as compared to intact or sham animals. The changes in D1 activity
      correlate with prostatic T(3) concentrations and Odc expression. Circulating
      levels of T(3) were not affected by consecutive ejaculations or by Smpx. These
      findings indicate that the postejaculatory increase in prostatic generation of
      T(3) depends on sympathetic input.

PMID- 20811015
TI  - Reduced fertility in vitro in mice lacking the cystatin CRES (cystatin-related
      epididymal spermatogenic): rescue by exposure of spermatozoa to dibutyryl cAMP
      and isobutylmethylxanthine.
AB  - The cystatin CRES (cystatin-related epididymal spermatogenic; Cst8) is the
      defining member of a reproductive subgroup of family 2 cystatins of cysteine
      protease inhibitors and is present in the epididymis and spermatozoa, suggesting
      roles in sperm maturation and fertilization. To elucidate the role of CRES in
      reproduction, mice lacking the Cst8 gene were generated and their fertility
      examined. Although both male and female Cst8(-/-) mice generated offspring in
      vivo, spermatozoa from Cst8(-/-) mice exhibited a profound fertility defect in
      vitro. Compared to spermatozoa from Cst8(+/+) mice, spermatozoa from Cst8(-/-)
      mice were unable to undergo a progesterone-stimulated acrosome reaction and had
      decreased levels of protein tyrosine phosphorylation, suggesting a defect in the
      ability of Cst8(-/-) spermatozoa to capacitate. Incubation of Cst8(-/-)
      spermatozoa with dibutyryl cAMP and 3-isobutyl-1-methylxanthine rescued the
      fertility defect, including the capacity for sperm protein tyrosine
      phosphorylation. Both untreated Cst8(+/+) and Cst8(-/-) spermatozoa, however,
      exhibited similar increased total levels of cAMP and protein kinase A (PKA)
      activity throughout the capacitation time course compared to spermatozoa
      incubated under noncapacitating conditions. Taken together, these results suggest
      that mice lacking CRES may have altered local levels of cAMP/PKA activity,
      perhaps because of improper partitioning or tethering of these signaling
      molecules, or that the CRES defect does not directly involve cAMP/PKA but other
      signaling pathways that regulate protein tyrosine phosphorylation and
      capacitation.

PMID- 20811017
TI  - Reflections on the 50th anniversary of the birth control pill.

PMID- 20811016
TI  - Lactobacillus rhamnosus GR-1 stimulates colony-stimulating factor 3 (granulocyte)
      (CSF3) output in placental trophoblast cells in a fetal sex-dependent manner.
AB  - Bacterial vaginosis is associated with a 1.4-fold increased risk of preterm
      birth. We have shown previously that Lactobacillus rhamnosus GR-1 supernatant up
      regulates interleukin 10 and down-regulates tumor necrosis factor-alpha output in
      lipopolysaccharide (LPS)-treated human primary placenta cultures in a fetal sex
      dependent manner. We hypothesize that lactobacilli also exert their anti
      inflammatory effect by up-regulation of colony-stimulating factor 3 (granulocyte)
      (CSF3), which is secreted from both immune and placental trophoblast cells, and
      that this activity is dependent on the sex of the fetus. Placental trophoblast
      cells were isolated from term elective cesarean section placentae using a Percoll
      gradient and separated from CD45(+) cells using magnetic purification. Cells were
      treated with LPS in the presence or absence of pretreatments with L. rhamnosus GR
      1 supernatant or chemical inhibitors of the intracellular signaling pathways.
      Phosphorylations of mitogen-activated protein kinase 14 (MAPK14, previously known
      as p38) and signal transducer and activator of transcription (STAT) 3 were
      measured by Western blot analysis, and levels of CSF3 were determined by ELISA.
      CSF3 output was increased only in the placental trophoblast cells of female
      fetuses treated with LPS, GR-1 supernatant, and a combination of both treatments.
      The GR-1 supernatant up-regulated the phosphorylation of STAT3 and MAPK14. CSF3
      output was inhibited by both Janus kinases (JAK) and MAPK14 inhibitors. None of
      the treatments was able to increase CSF3 output in either the pure trophoblast or
      the CD45(+) cell preparations alone. These results suggest an underlying
      mechanism for the sex difference in incidence of preterm birth and provide
      potential evidence for a therapeutic benefit of lactobacilli in reducing the risk
      of preterm labor.

PMID- 20811018
TI  - FDA approves first generic enoxaparin product.

PMID- 20811019
TI  - New botulinum toxin approved with REMS.

PMID- 20811020
TI  - Drug shortages mount in 2010.

PMID- 20811022
TI  - Pharmacists prepare for flu season: pediatric dosing, unpredictable demand pose
      challenges.

PMID- 20811023
TI  - Grade-point averages and class rankings in evaluation of pharmacy residency
      applicants.

PMID- 20811024
TI  - Defining pharmacy.

PMID- 20811025
TI  - Development and implementation of signs- and symptoms-based insulin adjustment
      algorithm.

PMID- 20811026
TI  - Maximizing your pharmacy brand.

PMID- 20811027
TI  - Where are risk evaluation and mitigation strategies headed?

PMID- 20811028
TI  - Issues related to risk evaluation and mitigation strategies in health-system
      pharmacy.

PMID- 20811029
TI  - Saxagliptin: a dipeptidyl peptidase-4 inhibitor for the treatment of type 2
      diabetes mellitus.
AB  - PURPOSE: The pharmacology, pharmacokinetics, efficacy, safety, and dosage and
      administration of saxagliptin are reviewed. SUMMARY: Saxagliptin is a selective,
      reversible inhibitor of dipeptidyl peptidase-4 (DPP-4) approved for the treatment
      of type 2 diabetes mellitus in adults. By inhibiting DPP-4, saxagliptin reduces
      the degradation of endogenous incretin hormones, resulting in increased glucose
      dependent insulin release and decreased glucagon secretion from the pancreas.
      Saxagliptin is rapidly absorbed after oral administration, and its
      pharmacokinetic profile allows for once-daily oral administration. Clinical
      trials of saxagliptin as monotherapy and as combination therapy with other oral
      antidiabetic medications including metformin, glyburide, pioglitazone, and
      rosiglitazone have demonstrated clinical benefits in various glycemic endpoints,
      including glycosylated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), and
      postprandial glucose (PPG) levels over 24 to 102 weeks of therapy. Due to its
      glucose-dependent mechanism of action, saxagliptin as monotherapy or in
      combination with metformin results in a low risk for hypoglycemia in patients
      with type 2 diabetes. Saxagliptin was generally well tolerated in clinical
      trials, with headache, upper-respiratory-tract infection, and urinary tract
      infection being the most common adverse events. Saxagliptin has demonstrated a
      low risk for drug-drug interactions. For patients with moderate or severe renal
      impairment or end-stage renal disease or patients taking a strong inhibitor of
      cytochrome P-450 isoenzyme 3A4 or 3A5, the recommended dosage is 2.5 mg once
      daily. CONCLUSION: Saxagliptin, a DPP-4 inhibitor approved for the treatment of
      type 2 diabetes, demonstrated safety and efficacy in lowering HbA(1c), FPG, and
      PPG levels as both monotherapy and in combination with other oral antidiabetic
      medications.

PMID- 20811030
TI  - Use of concentrated insulin human regular (U-500) for patients with diabetes.
AB  - PURPOSE: The efficacy and safety of and key clinical considerations for using U
      500 insulin human regular in the treatment of high-dose insulin-treated patients
      in a wide variety of settings are examined. SUMMARY: U-500 regular insulin has
      been available in the United States since 1952, but only recently has it become
      more commonly prescribed for patients requiring large amounts of insulin to
      improve their blood glucose control. This use coincides with the increasing rates
      of obesity and type 2 diabetes associated with significant insulin resistance,
      which can necessitate the need for doses of insulin exceeding 200 units/day.
      However, many health care professionals are relatively unfamiliar with this
      concentrated insulin formulation. U-500 regular insulin has a pharmacokinetic and
      pharmacodynamic profile that differs from U-100 human insulins and analogues.
      Although no randomized clinical trials using U-500 insulin have been performed,
      eight case series (involving 160 patients) have been published. Rare or
      infrequent occurrences of hypoglycemia with U-500 insulin have been reported. Of
      the medication errors associated with U-500 insulin, administration and
      dispensing errors occurred most frequently. With the increase in prescribing of U
      500 insulin, pharmacists must be aware of the complex issues involved with
      appropriate prescribing, dispensing, and provision of patient education to
      maximize patient safety and avoid administration errors and dosing confusion.
      CONCLUSION: U-500 insulin is efficacious and safe for patients with type 2
      diabetes who require a high dosage of insulin to control hyperglycemia. However,
      health care professionals should be well educated and vigilant about patient
      safety issues regarding the drug's prescription, dosing, and administration.

PMID- 20811031
TI  - Pharmacist's activities on a trauma response team in the emergency department.
AB  - PURPOSE: The interventions of a clinical pharmacist on an emergency department
      (ED) trauma response team were studied. METHODS: The study site was an academic,
      tertiary care hospital designated as a level 1 trauma center, with a clinical
      pharmacist present in the ED 40 hours per week. For a two-month period,
      interventions by the pharmacist in trauma cases were documented in an electronic
      quality-improvement database. RESULTS: A total of 304 interventions were
      recorded; the most common were dosage recommendations (60%) and provision of drug
      information (27%). The top five drug classes involved were analgesics, sedatives,
      antimicrobials, vaccines, and fluids. In 83% of the interventions, the pharmacist
      documented involvement in facilitating drug administration. CONCLUSION: A
      pharmacist participating on the ED trauma response team commonly provided dosage
      recommendations and drug information, facilitated drug administration, and
      optimized sedation, analgesia, and antimicrobial therapy.

PMID- 20811032
TI  - Stability of doripenem in polyvinyl chloride bags and elastomeric pumps.
AB  - PURPOSE: The stability of doripenem 500 and 1000 mg in polyvinyl chloride (PVC)
      bags and elastomeric pumps at various storage temperatures was evaluated.
      METHODS: Commercially available doripenem vials were reconstituted and mixed with
      either 0.9% sodium chloride injection or 5% dextrose injection to produce 100-mL
      solutions with concentrations of 5 and 10 mg/mL. Six replicate solutions in
      either PVC bags or elastomeric pumps were prepared. Bags were sampled immediately
      after preparation and stored at 25 degrees C, 4 degrees C, or -20 degrees C.
      Those stored at 25 degrees C were sampled for an additional 48 hours, and bags
      stored at 4 degrees C were sampled for 12 days. Bags frozen at -20 degrees C for
      14-28 days were allowed to thaw at either 25 degrees C for 4-6 hours or 4 degrees
      C for 24 hours and sampled for an additional 48 hours. Solutions retaining > or
      =90% of the initial concentration were considered stable. RESULTS: At 25 degrees
      C, both concentrations were stable for 24 hours in 0.9% sodium chloride injection
      and for 16 hours in 5% dextrose injection. At 4 degrees C, 5-mg/mL solutions were
      stable for 10 days in both 0.9% sodium chloride injection and 5% dextrose
      injection, while 10-mg/mL solutions were stable for 10 days in 0.9% sodium
      chloride injection and 7 days in 5% dextrose injection. A white precipitate,
      which returned to solution by shaking, was noted after thawing the frozen
      containers. Whether thawed at 4 degrees C or 25 degrees C, both 5- and 10-mg/mL
      solutions were stable for 16 hours at 25 degrees C. CONCLUSION: Doripenem 5- and
      10-mg/mL solutions were stable for 24 hours at 25 degrees C when diluted in 0.9%
      sodium chloride injection. When diluted in 5% dextrose injection, the stability
      of both concentrations of doripenem decreased to 16 hours at 25 degrees C. When
      stored at 4 degrees C, 5-mg/mL solutions in either 0.9% sodium chloride or 5%
      dextrose injection were stable for at least 10 days, and all solutions containing
      doripenem 10 mg/mL were stable for at least 7 days. Both concentrations of
      doripenem were stable for 16 hours when previously frozen and thawed at 25
      degrees C and 4 degrees C. The rate of doripenem degradation was similar between
      PVC and elastomeric containers.

PMID- 20811033
TI  - Guidelines for the safe handling of hazardous drugs: consensus recommendations.

PMID- 20811034
TI  - Risk evaluation and mitigation strategies: challenges and opportunities for
      health-system pharmacists.

PMID- 20811035
TI  - Dosing guidelines, not protocols, for managing warfarin therapy.

PMID- 20811036
TI  - Joint Commission's requirements for warfarin dosing guidelines.

PMID- 20811037
TI  - Strengthening relationships between pharmacy faculty members and clinical
      training sites.

PMID- 20811038
TI  - Insulin reciprocally regulates glucagon secretion in humans.
AB  - OBJECTIVE: We tested the hypothesis that an increase in insulin per se, i.e., in
      the absence of zinc, suppresses glucagon secretion during euglycemia and that a
      decrease in insulin per se stimulates glucagon secretion during hypoglycemia in
      humans. RESEARCH DESIGN AND METHODS: We measured plasma glucagon concentrations
      in patients with type 1 diabetes infused with the zinc-free insulin glulisine on
      three occasions. Glulisine was infused with clamped euglycemia (~95 mg/dl [5.3
      mmol/l]) from 0 to 60 min on all three occasions. Then, glulisine was
      discontinued with clamped euglycemia or with clamped hypoglycemia (~55 mg/dl [3.0
      mmol/l]) or continued with clamped hypoglycemia from 60 to 180 min. RESULTS:
      Plasma glucagon concentrations were suppressed by -13 +/- 3, -9 +/- 3, and -12 +/
      2 pg/ml (-3.7 +/- 0.9, -2.6 +/- 0.9, and -3.4 +/- 0.6 pmol/l), respectively,
      (all P < 0.01) during zinc-free hyperinsulinemic euglycemia over the first 60
      min. Glucagon levels remained suppressed following a decrease in zinc-free
      insulin with euglycemia (-14 +/- 3 pg/ml [-4.0 +/- 0.9 pmol/l]) and during
      sustained hyperinsulinemia with hypoglycemia (-14 +/- 2 pg/ml [-4.0 +/- 0.6
      pmol/l]) but increased to -3 +/- 3 pg/ml (-0.9 +/- 0.9 pmol/l) (P < 0.01)
      following a decrease in zinc-free insulin with hypoglycemia over the next 120
      min. CONCLUSIONS: These data indicate that an increase in insulin per se
      suppresses glucagon secretion and a decrease in insulin per se, in concert with a
      low glucose concentration, stimulates glucagon secretion. Thus, they document
      that insulin is a beta-cell secretory product that, in concert with glucose and
      among other signals, reciprocally regulates alpha-cell glucagon secretion in
      humans.

PMID- 20811040
TI  - Molecular profiling: moving away from tumor philately.
AB  - Despite the remarkable enhancements in breast cancer classification and
      characterization, an exhaustive comprehension of the underlying carcinogenic
      processes and an accurate prediction of its clinical behavior are yet to be
      achieved. On the wave of recent scientific advances and clinical findings, new
      cutting-edge technologies are poised to deliver an array of diverse molecular
      data that are expected to dramatically alter breast cancer diagnosis and
      treatment.

PMID- 20811039
TI  - Naloxone, but not valsartan, preserves responses to hypoglycemia after antecedent
      hypoglycemia: role of metabolic reprogramming in counterregulatory failure.
AB  - OBJECTIVE: Hypoglycemia-associated autonomic failure (HAAF) constitutes one of
      the main clinical obstacles to optimum treatment of type 1 diabetes. Neurons in
      the ventromedial hypothalamus are thought to mediate counterregulatory responses
      to hypoglycemia. We have previously hypothesized that hypoglycemia-induced
      hypothalamic angiotensin might contribute to HAAF, suggesting that the
      angiotensin blocker valsartan might prevent HAAF. On the other hand, clinical
      studies have demonstrated that the opioid receptor blocker naloxone ameliorates
      HAAF. The goal of this study was to generate novel hypothalamic markers of
      hypoglycemia and use them to assess mechanisms mediating HAAF and its reversal.
      RESEARCH DESIGN AND METHODS: Quantitative PCR was used to validate a novel panel
      of hypothalamic genes regulated by hypoglycemia. Mice were exposed to one or five
      episodes of insulin-induced hypoglycemia, with or without concurrent exposure to
      valsartan or naloxone. Corticosterone, glucagon, epinephrine, and hypothalamic
      gene expression were assessed after the final episode of hypoglycemia. RESULTS: A
      subset of hypothalamic genes regulated acutely by hypoglycemia failed to respond
      after repetitive hypoglycemia. Responsiveness of a subset of these genes was
      preserved by naloxone but not valsartan. Notably, hypothalamic expression of four
      genes, including pyruvate dehydrogenase kinase 4 and glycerol 3-phosphate
      dehydrogenase 1, was acutely induced by a single episode of hypoglycemia, but not
      after antecedent hypoglycemia; naloxone treatment prevented this failure.
      Similarly, carnitine palmitoyltransferase-1 was inhibited after repetitive
      hypoglycemia, and this inhibition was prevented by naloxone. Repetitive
      hypoglycemia also caused a loss of hypoglycemia-induced elevation of
      glucocorticoid secretion, a failure prevented by naloxone but not valsartan.
      CONCLUSIONS: Based on these observations we speculate that acute hypoglycemia
      induces reprogramming of hypothalamic metabolism away from glycolysis toward beta
      oxidation, HAAF is associated with a reversal of this reprogramming, and naloxone
      preserves some responses to hypoglycemia by preventing this reversal.

PMID- 20811041
TI  - Translational medicine and the value of biomarker qualification.
AB  - The gap between development of exploratory biomarkers and their acceptance in
      drug development and regulatory review is a hurdle in the development of better
      therapies. The U.S. Food and Drug Administration has developed a regulatory
      process for biomarker qualification to accelerate the process by which new
      biomarkers are integrated in the development of therapies.

PMID- 20811042
TI  - Platelet CD154 potentiates interferon-alpha secretion by plasmacytoid dendritic
      cells in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a systemic inflammatory autoimmune disease
      characterized by the involvement of multiple organs and an immune response
      against nuclear components. Although its pathogenesis remains poorly understood,
      type I interferon (IFN) and CD40 ligand (CD154) are known to contribute. Because
      platelets are involved in inflammatory processes and represent a major reservoir
      of CD154, we hypothesized that they participate in SLE pathogenesis. Here, we
      have shown that in SLE patients, platelets were activated by circulating immune
      complexes composed of autoantibodies bound to self-antigens through an Fc-gamma
      receptor IIa (CD32)-dependent mechanism. Further, platelet activation correlated
      with severity of the disease and activated platelets formed aggregates with
      antigen-presenting cells, including monocytes and plasmacytoid dendritic cells.
      In vitro, activated platelets enhanced IFN-alpha secretion by immune complex
      stimulated plasmacytoid dendritic cells through a CD154-CD40 interaction.
      Finally, in lupus-prone mice, depletion of platelets or administration of the
      P2Y(12) receptor antagonist (clopidogrel) improved all measures of disease and
      overall survival; transfusion of activated platelets worsened the disease course.
      Together, these data identify platelet activation as an important contributor to
      SLE pathogenesis and suggest that this process and its sequelae may provide a new
      therapeutic target.

PMID- 20811043
TI  - Overlap and effective size of the human CD8+ T cell receptor repertoire.
AB  - Diversity in T lymphocyte antigen receptors is generated by somatic rearrangement
      of T cell receptor (TCR) genes and is concentrated within the third
      complementarity-determining region 3 (CDR3) of each chain of the TCR heterodimer.
      We sequenced the CDR3 regions from millions of rearranged TCR beta chain genes in
      naive and memory CD8(+) T cells of seven adults. The CDR3 sequence repertoire
      realized in each individual is strongly biased toward specific V(beta)-J(beta)
      pair utilization, dominated by sequences containing few inserted nucleotides, and
      drawn from a defined subset comprising less than 0.1% of the estimated 5 x 10(11)
      possible sequences. Surprisingly, the overlap in the naive CD8(+) CDR3 sequence
      repertoires of any two of the individuals is approximately 7000-fold larger than
      predicted and appears to be independent of the degree of human leukocyte antigen
      matching.

PMID- 20811044
TI  - Age-dependent retinal iron accumulation and degeneration in hepcidin knockout
      mice.
AB  - PURPOSE: Iron dysregulation can cause retinal disease, yet retinal iron
      regulatory mechanisms are incompletely understood. The peptide hormone hepcidin
      (Hepc) limits iron uptake from the intestine by triggering degradation of the
      iron transporter ferroportin (Fpn). Given that Hepc is expressed in the retina
      and Fpn is expressed in cells constituting the blood-retinal barrier, the authors
      tested whether the retina may produce Hepc to limit retinal iron import. METHODS:
      Retinas of Hepc(-/-) mice were analyzed by histology, autofluorescence spectral
      analysis, atomic absorption spectrophotometry, Perls' iron stain, and
      immunofluorescence to assess iron-handling proteins. Retinal Hepc mRNA was
      evaluated through qPCR after intravitreal iron injection. Mechanisms of retinal
      Hepc upregulation were tested by Western blot analysis. A retinal capillary
      endothelial cell culture system was used to assess the effect of exogenous Hepc
      on Fpn. RESULTS: Hepc(-/-) mice experienced age-dependent increases in retinal
      iron followed by retinal degeneration with autofluorescent RPE, photoreceptor
      death, and subretinal neovascularization. Hepc(-/-) mice had increased Fpn
      immunoreactivity in vascular endothelial cells. Conversely, in cultured retinal
      capillary endothelial cells, exogenous Hepc decreased both Fpn levels and iron
      transport. The retina can sense increased iron levels, upregulating Hepc after
      phosphorylation of extracellular signal regulated kinases. CONCLUSIONS: These
      findings indicate that Hepc is essential for retinal iron regulation. In the
      absence of Hepc, retinal degeneration occurs. Increases in Hepc mRNA levels after
      intravitreal iron injection combined with Hepc-mediated decreases in iron export
      from cultured retinal capillary endothelial cells suggest that the retina may use
      Hepc for its tissue-specific iron regulation.

PMID- 20811046
TI  - Isolation and characterization of vitreous insulin-like growth factor binding
      proteins.
AB  - PURPOSE: Previous studies from this laboratory revealed that vitreous insulin
      like growth factor (IGF) biological activity increases in proliferative diabetic
      retinopathy and that this activity is normally attenuated by IGFBPs. The goal of
      this study was to identify and characterize the species involved. METHODS: Human
      and porcine vitreous, plasma, recombinant IGFBP-2, and IGFBP-3 were separated by
      gel electrophoresis. Functional IGFBPs were detected in Western ligand blots with
      biotinylated IGF-II. IGFBPs were identified using IGFBP-specific antibodies.
      RESULTS: Western ligand blots of normal vitreous and plasma detected two major
      proteins at ~35 kDa and ~29 kDa. Western blot analysis of human and porcine
      vitreous and plasma confirmed the identity of the ~35-kDa band as IGFBP-2 and the
      ~29-kDa band as a fragment of IGFBP-3. Western blot and Western ligand blot
      analyses of vitreous and plasma proteins separated by two-dimensional gel
      electrophoresis revealed that the IGFBP-3 fragments in vitreous and plasma have
      virtually identical profiles. Lyase digestion revealed that the ~29-kDa IGFBP-3
      fragment is a glycoprotein with a peptide core of ~25 kDa. N-terminal sequence
      data obtained from vitreous IGFBP-3 revealed that the protein is proteolytically
      truncated at the C terminus. CONCLUSIONS. Normal human and porcine vitreous
      contain two major IGFBPs, IGFBP-2 and an ~29-kDa fragment of IGFBP-3. Both IGFBPs
      retain biological activity, and IGFBP-3 has one or more glycosylation sites with
      a protein core of ~25 kDa. Systematic comparisons indicate that the vitreous
      IGFBP-3 is similar to and perhaps identical with a previously described IGFBP-3
      fragment in plasma with reduced growth factor affinities.

PMID- 20811047
TI  - The phenotype of Severe Early Childhood Onset Retinal Dystrophy (SECORD) from
      mutation of RPE65 and differentiation from Leber congenital amaurosis.
AB  - PURPOSE: To describe in detail the characteristic clinical phenotype and
      electrophysiological features of Severe Early Childhood Onset Retinal Dystrophy
      (SECORD) caused by mutation of RPE65. METHODS: Ophthalmological examination,
      color fundus photography, visual field testing, detailed electrophysiological
      assessment, and screening of RPE65 were undertaken in five subjects. Selected
      patients also had spectral domain optical coherence tomography. RESULTS: All five
      patients had life-long, extremely poor night vision. Variable degrees of
      nystagmus were present; three cases lacked nystagmus at the time of assessment.
      Bilateral disc drusen were evident in three subjects. While case 1 had an
      undetectable electroretinogram and features supporting a diagnosis of Leber
      congential amaurosis (LCA) as an infant, her level of acuity and function into
      the second decade of life was more consistent with SECORD. In two cases, both
      vision and electrophysiological responses were seen to improve into the second
      decade of life. The objective demonstration of improved retinal function over
      time, with electrophysiological testing, has not been previously reported. Cases
      4 and 5 had evidence of fine white retinal dots. The authors propose that these
      represent abnormal accumulations of retinyl esters, as has been demonstrated in
      animal models, and has also been observed as lipid droplets within the retinal
      pigment epithelium (RPE). These white dots were seen to fade with time in the
      patients and were replaced by RPE changes. CONCLUSIONS: The identification of
      patients with mutations in RPE65 has attained greater significance now that gene
      replacement trials have begun. The features presented in this article assist in
      the recognition of this form of LCA/SECORD.

PMID- 20811045
TI  - The role of RPE cell-associated VEGF189 in choroidal endothelial cell
      transmigration across the RPE.
AB  - PURPOSE: To determine the role of vascular endothelial growth factor 189
      (VEGF189) in choroidal endothelial cell (CEC) migration across the retinal
      pigment epithelium (RPE) and to explore the molecular mechanisms involved.
      METHODS: Using real-time PCR, the expression of VEGF splice variants VEGF121,
      VEGF165, and VEGF189 was determined in human RPE from donor eyes, cultured human
      RPE in contact with CECs exposed to hydrogen peroxide (H2O2) or hypoxia, and
      RPE/choroid specimens from mice treated with laser to induce choroidal
      neovascularization (CNV). Activation of VEGF receptors (VEGFRs), phosphoinositol
      3-kinase (PI-3K) or Rac1 was measured in CECs cocultured in contact with RPE
      exposed to peroxide or silenced for VEGF189 expression. Migration of CECs across
      the RPE was determined using fluorescence microscopy. RESULTS: VEGF189 expression
      was increased in human RPE from aged compared with young donor eyes and from
      mouse RPE/choroids after laser to induce CNV. VEGF189 was also upregulated in
      human RPE challenged with peroxide, hypoxia, or cultured in contact with CECs.
      CEC migration across RPE was greater after RPE exposure to peroxide to induce
      VEGF189; VEGFR2 and Rac1 activities were also increased in these CECs. When CECs
      were cocultured with RPE silenced for VEGF189, VEGFR2 and Rac1 activities in CECs
      were significantly reduced, as was CEC migration across the RPE. Inhibition of
      Rac1 activity significantly inhibited CEC transmigration without affecting PI-3K
      activity. CONCLUSIONS: RPE-derived cell-associated VEGF189 facilitates CEC
      transmigration by Rac1 activation independently of PI-3K signaling and may have
      importance in the development of neovascular AMD.

PMID- 20811048
TI  - Induction of arginase II mRNA by nitric oxide using an in vitro model of gyrate
      atrophy of choroid and retina.
AB  - PURPOSE: The authors previously reported ornithine cytotoxicity in ornithine
      delta-aminotransferase (OAT)-deficient human retinal pigment epithelial (RPE)
      cells as an in vitro model of gyrate atrophy of the choroid and retina (GA).
      Given that RPE cells are severely damaged by arginine combined with ornithine,
      they investigated the role of arginine metabolism using that in vitro model.
      METHODS: Human telomerase reverse transcriptase (hTERT)-RPE cells were incubated
      with ornithine or other agents in the presence of 5-fluoromethylornithine (5
      FMO), an OAT-specific inhibitor. mRNA expression was determined by quantitative
      real-time polymerase chain reaction, and the concentration of nitric oxide (NO)
      was quantified using a Griess assay. Furthermore, cytotoxicity was examined by
      morphologic observations and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) colorimetric assays, with the effect of arginase II examined using
      short interfering (si) RNA for arginase II and S-(2-boronoethyl)-L-cysteine
      (BEC), an arginase inhibitor. RESULTS: NO production in 5-FMO-treated hTERT-RPE
      cells was increased by ornithine, and the NO donors S-nitroso-N-acetyl-DL
      penicillamine (SNAP) and S-nitrosoglutathione induced cytotoxicity. Ornithine
      increased the expression of arginase II mRNA in 5-FMO-treated cells. Arginase II
      upregulation was partially inhibited by an NO synthase inhibitor, N(G)-nitro-L
      arginine methyl ester, which was mimicked by SNAP. Arginase II siRNA and BEC
      enhanced ornithine cytotoxicity, and arginase II silencing resulted in a further
      increase in NO production. CONCLUSIONS: These results demonstrate that NO is
      produced in our in vitro GA model, which induced cytotoxicity of RPE cells and
      upregulation of arginase II. NO may be involved in RPE degeneration in GA through
      the regulation of arginase II mRNA expression.

PMID- 20811049
TI  - The nuclear-factor kappaB pathway is activated in pterygium.
AB  - PURPOSE: Pterygium is a prevalent ocular surface disease with unknown
      pathogenesis. The authors investigated the role of nuclear factor kappa B (NF
      kappaB) transcription factors in pterygium. METHODS: Surgically excised primary
      pterygia were studied compared with uninvolved conjunctiva tissues. NF-kappaB
      activation was evaluated using Western blot analysis, ELISA, and DNA-binding
      assays. Primary pterygium fibroblasts were treated with TNF-alpha (20 ng/mL), and
      NF-kappaB activation was evaluated using immunocytochemistry, Western blot
      analysis, phospho-IkappaBalpha ELISA, and DNA-binding assays. TNF-alpha
      stimulation of NF-kappaB target genes RelB, NFKB2, RANTES, MCP-1, ENA-78, MMP-1,
      MMP-2, and MMP-3 in pterygium fibroblasts was compared with that in primary tenon
      fibroblasts by real-time PCR. RESULTS: Phosphorylation of IkappaBalpha (Ser32)
      was increased in pterygia tissues compared with uninvolved conjunctiva tissues,
      as determined by Western blot analysis and ELISA. IkappaBalpha expression was
      decreased, whereas nuclear RelA and p50 DNA-binding capacities were increased.
      Within 30 minutes of treatment with TNF-alpha, pterygium fibroblasts showed
      increased IkappaBalpha phosphorylation and nuclear translocation of RelA and p50.
      Treatment with TNF-alpha beyond 12 hours resulted in increased nuclear expression
      of RelB, p100, and p52. Furthermore, the upregulation of RANTES, MCP-1, ENA-78,
      MMP-1, MMP-2, and MMP-3 expression was more pronounced in TNF-alpha-treated
      pterygium fibroblasts than in tenon fibroblasts. CONCLUSIONS: The NF-kappaB
      pathway is shown for the first time to be activated in pterygia tissues compared
      with normal conjunctiva tissues. Stimulation by the inflammatory cytokine TNF
      alpha can activate both canonical and noncanonical NF-kappaB pathways in
      pterygium fibroblasts with concomitant upregulation of NF-kappaB target genes.

PMID- 20811051
TI  - Influence of optical defocus on peripheral vision.
AB  - PURPOSE: Peripheral optical corrections are often thought to give few visual
      benefits beyond improved detection acuity. However, patients with central visual
      field loss seem to benefit from peripheral correction, and animal studies suggest
      a role for peripheral vision in the development of myopia. This study was
      conducted to bridge this gap by systematically studying the sensitivity to
      optical defocus in a wide range of peripheral visual tasks. METHODS: The spatial
      frequency threshold for detection and resolution in high and low contrast with
      stationary and drifting gratings were measured off-axis (20 degrees  nasal visual
      field) in five subjects with a peripheral optical correction that was varied
      systematically +/-4 D. RESULTS: All visual tasks, except high-contrast
      resolution, were sensitive to optical defocus, particularly low-contrast
      resolution with an increase of up to 0.227 logMAR/D. The two myopic subjects
      exhibited a very low sensitivity to defocus by negative lenses for low-contrast
      tasks, whereas all subjects were equally affected by myopic defocus. Contrary to
      expectations, drifting gratings made little difference overall. CONCLUSIONS:
      Optical defocus as low as 1 D has a large impact on most peripheral visual tasks,
      with high-contrast resolution being the exception. Since the everyday visual
      scenery consists of objects at different contrast levels, it is understandable
      that persons with central visual field loss are helped by correction of
      peripheral refractive errors. The asymmetry in sensitivity to peripheral optical
      defocus in low-contrast tasks that was experienced by the myopic subjects in this
      study merits further investigation.

PMID- 20811052
TI  - Optokinetic nystagmus suppression as an index of the allocation of visual
      attention.
AB  - PURPOSE: To use the suppression of optokinetic nystagmus (OKN) as an objective
      measure of subjects' ability to distribute their visual attention to different
      elements-static or dynamic, simple or complex-in their visual environment.
      METHODS: Large-field, constant-velocity projected images, along with a stationary
      central fixation target were presented to 25 young participants (13 women).
      Images were either black O's with a few X's or red C's, blue T's, and a few red
      T's, with the X's and red T's as the search targets. Stationary targets at either
      0 degrees  or +/-12.5 degrees  were either blinking squares or a rapid succession
      of colored shapes-blinks or green stars were the target events. Central fixation
      was maintained at all times. OKN gain was calculated for all tasks and analyzed
      in a mixed 4-way ANOVA, with the sex of the subjects as the group variable and
      dynamism, location, and complexity as within-subject effects. RESULTS: There was
      no effect of sex; all three main within-subject effects were significant, as were
      the two-way interactions between them and an interaction between dynamism and
      sex. The most striking result was that there was little difference across static
      tasks but that dynamic tasks showed significantly more OKN breakthrough,
      particularly for the complex search presented centrally. CONCLUSIONS: In this
      group of normal-sighted young subjects, OKN breakthrough was sensitive to a range
      of stimulus characteristics. This finding allows a single outcome measure to be
      used across a wide range of possible tasks and may be useful in assessing the
      effects of age and disease.

PMID- 20811050
TI  - Sigma receptor 1 modulates endoplasmic reticulum stress in retinal neurons.
AB  - PURPOSE: To investigate the mechanism of sigma receptor 1 (sigmaR1)
      neuroprotection in retinal neurons. METHODS: Oxidative stress, which is
      implicated in diabetic retinopathy, was induced in mouse primary ganglion cells
      (GCs) and RGC-5 cells, and the effect of the sigmaR1 ligand (+)-pentazocine on
      pro- and anti-apoptotic and endoplasmic reticulum (ER) stress gene expression was
      examined. Binding of sigmaR1 to BiP, an ER chaperone protein, and sigmaR1
      phosphorylation status were examined by immunoprecipitation. Retinas were
      harvested from Ins2Akita/+ diabetic mice treated with (+)-pentazocine, and the
      expression of ER stress genes and of the retinal transcriptome was evaluated.
      RESULTS: Oxidative stress induced the death of primary GCs and RGC-5 cells. The
      effect was decreased by the application of (+)-pentazocine. Stress increased
      sigmaR1 binding to BiP and enhanced sigmaR1 phosphorylation in RGC-5 cells. BiP
      binding was prevented, and sigmaR1 phosphorylation decreased in the presence of
      (+)-pentazocine. The ER stress proteins PERK, ATF4, ATF6, IRE1alpha, and CHOP
      were upregulated in RGC-5 cells during oxidative stress, but decreased in the
      presence of (+)-pentazocine. A similar phenomenon was observed in retinas of
      Ins2Akita/+ diabetic mice. Retinal transcriptome analysis of Ins2Akita/+ mice
      compared with wild-type revealed differential expression of the genes critically
      involved in oxidative stress, differentiation, and cell death. The expression
      profile of those genes was reversed when the Ins2Akita/+ mice were treated with
      (+)-pentazocine. CONCLUSIONS: In retinal neurons, the molecular chaperone sigmaR1
      binds BiP under stressful conditions; (+)-pentazocine may exert its effects by
      dissociating sigmaR1 from BiP. As stress in retinal cells increases,
      phosphorylation of sigmaR1 is increased, which is attenuated when agonists bind
      to the receptor.

PMID- 20811053
TI  - PI 3-kinase/Rac1 and ERK1/2 regulate FGF-2-mediated cell proliferation through
      phosphorylation of p27 at Ser10 by KIS and at Thr187 by Cdc25A/Cdk2.
AB  - PURPOSE: To determine the mechanism of p27 phosphorylation through common and
      differential pathways triggered by FGF-2 in corneal endothelial cells (CECs).
      METHODS: A GTP pull-down assay was performed to identify Rac1-GTP. Expression and
      activation of protein were analyzed by immunoblotting. Cell proliferation was
      measured by an MTT assay. Transfection of CECs with kinase-interacting stathmin
      (KIS) siRNA was performed. RESULTS: FGF-2 activated Rac1 through Akt, and Rac1
      inhibitor greatly inhibited the FGF-2-stimulated cell proliferation. Rac1
      inhibitor reduced p27 phosphorylation at both serine 10 (Ser10) and threonine 187
      (Thr187). ERK1/2 was also involved in FGF-2-stimulated CEC proliferation and
      phosphorylation of p27 at Ser10 and Thr187 in parallel to phosphatidylinositol
      (PI) 3-kinase. In both PI 3-kinase/Rac1 and ERK1/2 pathways, Ser10 of p27 is
      phosphorylated by KIS, confirmed by siRNA to KIS, which subsequently hampered the
      FGF-2-stimulated cell proliferation, while Thr187 of p27 was phosphorylated
      through Cdk2 activated by Cdc25A. Cdc25A inhibitor blocked activation of Cdk2,
      phosphorylation of p27 at Thr187, and cell proliferation. FGF-2 induced both KIS
      and Cdc25A during the G1 phase; the maximum KIS expression was observed 4 hours
      after FGF-2 stimulation, while the maximum Cdc25A expression was observed at 12
      hours. Blockade of ERK1/2 and Rac1 greatly reduced KIS and Cdc25A expression.
      CONCLUSIONS: Results suggest that FGF-2 uses both PI 3-kinase/Rac1 and ERK
      pathways for cell proliferation; two signals employ common pathways for
      phosphorylating p27 according to the sites (KIS for Ser10 and Cdc25A/Cdk2 for
      Thr187) with their characteristic kinetics (early G1 for Ser10 and late G1 for
      Thr187).

PMID- 20811055
TI  - Effects of photodynamic therapy on rapidly growing nontuberculous mycobacteria
      keratitis.
AB  - PURPOSE: The authors investigated the antimicrobial effect of methylene blue (MB)
      mediated photodynamic therapy (PDT) on Mycobacterium fortuitum keratitis.
      METHODS: In the in vitro study, the mycobacterial suspension and colonies were
      treated with the following: no MB, no light (normal control); MB and no light
      (dye control); light and no MB (light control); MB and light (PDT). Morphologic
      characteristics were examined by transmission electron microscopy. The
      bactericidal effects of combined PDT and antibiotic therapy (ciprofloxacin,
      moxifloxacin, and amikacin) were determined using the broth microdilution
      technique. Twenty-one rabbits with Mycobacterium keratitis were randomly divided
      into three groups (no treatment, topical amikacin treatment, and PDT combined
      with amikacin treatment). The clinical features of keratitis were scored and
      graded before treatment and before euthanatization. The diseased corneas were
      trephined for quantitative bacteriologic analysis to determine the antibacterial
      efficacy of the treatment. RESULTS: In the in vitro tests, the bacterial count
      had a 2-log reduction immediately after PDT treatment at 100 J/cm(2) with 10(-3)%
      MB. After PDT at 100 J/cm(2) with 10(-2)% MB, almost no viable bacteria were
      detected. PDT had a synergistic antimicrobial effect in combination with
      antibiotics. The phototoxicity occurred in the cytoplasm first and then disrupted
      the mycobacterial cell walls by lysis. In the rabbit keratitis model, combined
      PDT resulted in significantly less bacterial burden (P < 0.01) than in the
      amikacin group. CONCLUSIONS: This study demonstrated the effectiveness of MB
      mediated PDT against Mycobacterium fortuitum. PDT could be a potential
      alternative treatment for nontuberculous mycobacterial corneal infections.

PMID- 20811054
TI  - CXCL10 is required to maintain T-cell populations and to control parasite
      replication during chronic ocular toxoplasmosis.
AB  - PURPOSE: Toxoplasma gondii is a major cause of ocular disease, which can lead to
      permanent vision loss in humans. T cells are critically involved in parasite
      control, but little is known about the molecules that promote T-cell trafficking
      and migration in the retina. Thus, the aim of this study was to image and dissect
      the T-cell response during chronic toxoplasmic retinochoroiditis. METHODS:
      C57BL/6 mice were infected with the Me49 strain of T. gondii, and T cells that
      infiltrated the eye were analyzed by flow cytometry and imaged using multiphoton
      microscopy. IFN-gamma, CXCL9, CXCL10, and CXCR3 mRNA levels were measured by real
      time PCR. To investigate the role of CXCL10, mice were treated with anti-CXCL10
      antibodies, and histopathology and immunohistochemistry were performed to monitor
      changes in pathology, cellular infiltration, and parasite burden in the eye.
      RESULTS: Infection with T. gondii leads to the infiltration of highly activated
      motile T cells into the eye. These cells express CXCR3 and are capable of
      producing IFN-gamma and TNF-alpha, and CD8+ T cells express granzyme B. The
      expression of CXCL9 and CXCL10 in the retina was significantly upregulated during
      chronic infection. Treatment of chronically infected mice with anti-CXCL10
      antibodies led to decreases in the numbers of CD3+, CD4+, and CD8+ T cells and
      the amount of IFN-gamma mRNA expression in the retina and an increase in
      replicating parasites and ocular pathology. CONCLUSIONS: The maintenance of the T
      cell response and the control of T. gondii in the eye during chronic infection is
      dependent on CXCL10.

PMID- 20811056
TI  - Task-specific fixation behavior in macular disease.
AB  - PURPOSE: Persons with central scotomas frequently use a preferred retinal locus
      (PRL) in place of the damaged fovea to fixate a target. Here the authors use a
      novel statistical technique to determine whether the retinal locus used for
      fixating a point target is the same as that used for reading words. METHODS: Nine
      subjects with established macular disease and bilateral central scotomas were
      recruited. The retinal area used for fixating a point target and words of text
      was measured using a microperimeter. A nonparametric spatial statistical
      technique was used to identify whether fixation points were the same for each of
      these two tasks. RESULTS: The spatial distribution of fixation points was
      different for point fixation and word reading in all subjects with macular
      disease (P<0.01). Fixation stability was also poorer for the word reading task
      than the fixation task (P<0.05). For control subjects without macular disease,
      the distribution of fixation was the same for each task (P>0.3). CONCLUSIONS:
      Fixation behavior in persons with macular disease is not the same for fixating a
      point target and for fixating words in a reading task. It cannot be assumed that
      measuring a patient's fixation to a discrete point target accurately simulates
      their fixation performance on other tasks.

PMID- 20811057
TI  - Altered ganglioside expression modulates the pathogenic mechanism of thyroid
      associated ophthalmopathy by increase in hyaluronic acid.
AB  - PURPOSE: The aim of this study was to determine the role of gangliosides in
      pathogenic mechanisms of thyroid-associated ophthalmopathy (TAO). METHODS: The
      gangliosides profile and mRNA level of sialyltransferases of the orbital tissues
      from TAO patients (n = 5) and non-TAO subjects (n = 4) were investigated. In
      addition, the effect of exogenous gangliosides on the expression of hyaluronic
      acid was examined in orbital fibroblasts. For in vitro experiments, we used four
      different strains of cells obtained from non-TAO subjects with at least three
      replicates for each strain. RESULTS: Trisialoganglioside 1b (GT1b) was
      significantly overexpressed in the orbital tissue of TAO patients compared with
      control tissue, whereas no significant difference was observed for either
      monosialoganglioside 1 (GM1) or disialoganglioside 1a (GD1a) by digital analyses
      of immunohistochemical images. Moreover, mRNA levels of sialyltransferase (SAT)-I
      and SAT II were increased in TAO patients compared with control. Exogenous GT1b
      strongly induced the morphologic changes related to an accumulation of sparse
      flocculent precipitates in lysosomes and increased the extracellular hyaluronic
      acid level in orbital fibroblasts with the induction of hyaluronic acid synthase,
      which were less by GD1a but not by GM1. The GT1b-induced morphologic changes of
      cells were due, at least in part, to an increase of intracellular hyaluronic
      acid. Co-treatment of hyaluronidase nicely attenuated the morphologic changes in
      orbital fibroblasts. Thy-1(+) orbital fibroblasts were more capable of producing
      hyaluronic acid by exogenous GT1b. CONCLUSIONS: The results suggest that
      gangliosides, particularly GT1b, may play a role in the pathologic mechanisms of
      TAO by stimulating an increase in hyaluronic acid.

PMID- 20811058
TI  - A survey of DNA variation of C2ORF71 in probands with progressive autosomal
      recessive retinal degeneration and controls.
AB  - PURPOSE: Mutations of C2ORF71 have recently been reported to be associated with
      autosomal recessive (AR) retinitis pigmentosa (RP) in humans and with visual
      defects in zebrafish. C2ORF71 is located on 2p23.2 and encodes a 1288-amino-acid
      protein of unknown function, predominately expressed in the photoreceptors. The
      study was conducted to determine the prevalence of mutations in C2ORF71 in a
      cohort of probands with AR retinal degeneration and to detect coding sequence
      variation in controls. METHODS: A combination of high-resolution DNA melting
      (HRM) analysis and automated DNA sequencing was used to screen for C2ORF71 in 286
      affected unrelated individuals. Among them, 95 subjects had Leber congenital
      amaurosis, and 191 had AR RP. In a similar fashion, 151 European and 40 South
      Asian control DNAs were screened. RESULTS: Overall, 40 DNA sequence variants were
      detected, with 17 novel polymorphisms found in the control subjects (8 missense,
      7 synonymous, and 2 other). Importantly, 11 novel sequence variants (6 missense
      and 5 synonymous) in 20 alleles were detected in the cohort of patients but not
      in the controls. Only one proband was a compound heterozygote but segregation
      analysis revealed her unaffected father to be homozygous for one of the putative
      mutations. CONCLUSIONS: C2ORF71 is a highly polymorphic gene (average
      heterozygosity of coding region in controls: 2.118 * 10(-3)) with many rare
      variants that confound mutation detection. Further analysis will determine the
      spectrum of retinal disease caused by mutations in C2ORF71 and distinguish true
      pathogenic alleles from the high background of polymorphism elucidating the role
      of this rare cause of RP in the visual process.

PMID- 20811059
TI  - Detection of M2-macrophages in uveal melanoma and relation with survival.
AB  - PURPOSE: The presence of a high number of infiltrating macrophages in uveal
      melanoma is associated with a bad prognosis. However, there are several known
      types of macrophages, of which the M2 is considered to be proangiogenic and tumor
      promoting. This study was conducted to determine whether the tumor-infiltrating
      macrophages in uveal melanoma are of this M2 subtype. METHODS: Macrophages were
      identified in sections from 43 uveal melanomas by immunofluorescence
      histochemistry, using monoclonal antibodies directed against CD68 and CD163. The
      immunopositive cell density was measured visually and with a confocal microscope
      and calculated per square millimeter. Results were compared with clinical and
      tumor characteristics. RESULTS: Infiltrating macrophages in uveal melanoma were
      predominantly CD68(+)CD163(+), thus of the M2 phenotype. The density of CD68(+),
      CD163(+), and CD68(+)CD163(+) cells was significantly increased in uveal
      melanomas with monosomy 3 compared with cases with disomy of chromosome 3 and was
      associated with ciliary body involvement. High CD68(+)CD163(+) staining was
      associated with an increased microvascular density. Survival was significantly
      better among patients with low CD68(+) and CD68(+)CD163(+) staining. CONCLUSION:
      The main type of macrophage present in uveal melanoma was the M2 type. Tumors
      with monosomy of chromosome 3 contained a higher number of M2-macrophages than
      tumors with disomy of chromosome 3. Infiltration of M2-type macrophages gives a
      worse prognosis for survival. As M2-type macrophages are proangiogenic, a high
      density of these cells may contribute to the previously noticed positive
      association between the density of CD68(+) macrophages and blood vessels.

PMID- 20811060
TI  - Effect of disease severity and optic disc size on diagnostic accuracy of RTVue
      spectral domain optical coherence tomograph in glaucoma.
AB  - PURPOSE: To evaluate the effect of disease severity and optic disc size on the
      diagnostic accuracies of optic nerve head (ONH), retinal nerve fiber layer
      (RNFL), and macular parameters with RTVue (Optovue, Fremont, CA) spectral domain
      optical coherence tomography (SDOCT) in glaucoma. METHODS: 110 eyes of 62 normal
      subjects and 193 eyes of 136 glaucoma patients from the Diagnostic Innovations in
      Glaucoma Study underwent ONH, RNFL, and macular imaging with RTVue. Severity of
      glaucoma was based on visual field index (VFI) values from standard automated
      perimetry. Optic disc size was based on disc area measurement using the
      Heidelberg Retina Tomograph II (Heidelberg Engineering, Dossenheim, Germany).
      Influence of disease severity and disc size on the diagnostic accuracy of RTVue
      was evaluated by receiver operating characteristic (ROC) and logistic regression
      models. RESULTS: Areas under ROC curve (AUC) of all scanning areas increased (P <
      0.05) as disease severity increased. For a VFI value of 99%, indicating early
      damage, AUCs for rim area, average RNFL thickness, and ganglion cell complex-root
      mean square were 0.693, 0.799, and 0.779, respectively. For a VFI of 70%,
      indicating severe damage, corresponding AUCs were 0.828, 0.985, and 0.992,
      respectively. Optic disc size did not influence the AUCs of any of the SDOCT
      scanning protocols of RTVue (P > 0.05). Sensitivity of the rim area increased and
      specificity decreased in large optic discs. CONCLUSIONS: Diagnostic accuracies of
      RTVue scanning protocols for glaucoma were significantly influenced by disease
      severity. Sensitivity of the rim area increased in large optic discs at the
      expense of specificity.

PMID- 20811061
TI  - Innervation of the mouse cornea during development.
AB  - PURPOSE: Dense innervation of the cornea is important for maintaining its
      homeostasis and transparency. Although corneal nerves have been well studied in
      adults, little is known about mammalian corneal innervation during development.
      This study provides a detailed profile of nerves at various stages of mouse
      cornea development. METHODS: Mouse heads and corneas were collected at various
      stages of development including embryonic days (E)12.5 to E16.5, postnatal days
      (P)0, P10, three weeks after birth, and the adult. Corneas were immunostained
      with an anti-neuron-specific beta-tubulin antibody (TUJ1). Fluorescently labeled
      nerves in whole-mount tissues and sections were imaged and analyzed for their
      axonal projections during eye development. RESULTS: The first nerve bundles
      appear at the periphery of the anterior portion of the eye by E12.5. Initial
      projection into the stroma occurs at E13.5 without formation of a pericorneal
      nerve ring. Between E13.5 and E16.5, nerve bundles project directly into the
      periphery of the presumptive cornea stroma. They branch repeatedly as they extend
      toward the cornea center and epithelium. Concomitantly, nerve bundles originating
      from four quadrants of the eye bifurcate into smaller branches that innervate the
      entire stroma. The first epithelial innervation occurs at E16.5. Epithelial
      nerves arrange into patterns that project toward the center subsequently forming
      a swirl at three weeks after birth, which becomes more pronounced in adults.
      CONCLUSIONS: Nerve bundles that arise from four quadrants of the eye innervate
      the mouse cornea. The nerve bundles directly innervate the stroma without forming
      a pericorneal nerve ring. Radial arrangement of epithelial nerves gradually
      becomes centrally oriented, subsequently forming a swirl pattern.

PMID- 20811062
TI  - Retinal ganglion cell loss in a rat ocular hypertension model is sectorial and
      involves early optic nerve axon loss.
AB  - PURPOSE: Previous analyses of the DBA/2J mouse glaucoma model show a sectorial
      degeneration pattern suggestive of an optic nerve head insult. In addition, there
      are large numbers of retinal ganglion cells (RGCs) that cannot be retrogradely
      labeled but maintain RGC gene expression, and many of these have somatic
      phosphorylated neurofilament labeling. Here the authors further elucidate these
      features of glaucomatous degeneration in a rat ocular hypertension model.
      METHODS: IOP was elevated in Wistar rats by translimbal laser photocoagulation.
      Retina whole mounts were analyzed for Sncg mRNA in situ hybridization, fluorogold
      (FG) retrograde labeling, and immunohistochemistry for phosphorylated
      neurofilaments (pNF) at 10 and 29 days after IOP increase. A novel automatic
      method was used to estimate axon numbers in plastic sections of optic nerves.
      RESULTS: Sncg mRNA was confirmed as a specific marker for RGCs in rat. Loss of
      RGCs after IOP elevation occurred in sectorial patterns. Sectors amid
      degeneration contained RGCs that were likely disconnected because these had pNF
      in their somas and dendrites, were not labeled by FG, and were associated with
      reactive plasticity within the retina. Most of the axon loss within the optic
      nerve already occurred by 10 days after the onset of IOP elevation. CONCLUSIONS:
      These data demonstrate that the pattern of RGC loss after laser-induced ocular
      hypertension in rats is similar to that previously reported in DBA/2J mice. The
      results support the view that in glaucoma RGC axons are damaged at the optic
      nerve head and degenerate within the optic nerve before there is loss of RGC
      somas.

PMID- 20811063
TI  - Investigation of the association between Helicobacter pylori infection and normal
      tension glaucoma.
AB  - PURPOSE: To investigate whether Helicobacter pylori infection is associated with
      normal tension glaucoma (NTG). METHODS: One hundred consecutive NTG patients
      (group 1) from an outpatient glaucoma clinic were enrolled. Medical records of
      the 88 control participants (control 1) of the outpatient clinic, and 104 NTG
      patients (group 2) and 1116 healthy controls (control 2) (1220 subjects in total)
      from a primary health care center were reviewed retrospectively to compare the
      results. Serum samples from all subjects were analyzed for the presence of H.
      pylori-specific immunoglobulin G antibodies using ELISA. The distributions of
      serologic H. pylori test results of the NTG patients and control subjects were
      compared, and possible associations between clinical phenotypes and positive
      serologic results were assessed. Bilaterality of NTG patients was also analyzed.
      RESULTS: NTG patients had significantly more positive serologic results than did
      the healthy controls. There were significant differences between group 1 and
      control 1 patients (P = 0.020; odds ratio [OR], 2.05), group 1 and control 2
      patients (P = 0.016; OR, 1.73), and group 2 and control 2 patients (P = 0.008;
      OR, 1.83). However, no significant association was found between clinical
      characteristics and a positive serologic result for H. pylori in NTG patients.
      CONCLUSIONS: This study suggests that H. pylori infection may be associated with
      an increased risk for NTG. H. pylori may play a role in the development or
      progression of NTG as a secondary aggravating factor because of the coexistence
      of other main causes or it may be the primary cause.

PMID- 20811064
TI  - Age-severity relationships in families linked to FCD2 with retroillumination
      photography.
AB  - PURPOSE: Fuchs corneal dystrophy (FCD) is a progressive disorder of the corneal
      endothelium and is pathologically defined by the presence of guttae, which are
      excrescences of the Descemet membrane. The present study was undertaken to
      investigate the age-severity relationship of the FCD2-linked disease phenotype
      using retroillumination photography and to compare it with the characteristics of
      FCD1. METHODS: Two large families with multiple affected members were recruited.
      Exclusion analyses of the known late-onset FCD loci were completed with closely
      spaced STR markers, whereas genes associated with early- and late-onset FCD were
      investigated by bidirectional sequencing. Haplotypes were constructed, and two
      point LOD scores were calculated. To document age-severity relationships,
      retroillumination photographs were acquired from members of both families.
      RESULTS: Parametric linkage and haplotype analysis mapped both families to FCD2
      with significant two-point LOD scores. A total of 70,249 guttae were counted in
      14 persons from both families. A significant increase in guttae density in the
      inferotemporal region (P = 0.016) was observed, a pattern similarly observed in a
      family linked to FCD1. Similarly, FCD2-linked families display an exponential
      trend in severity with age, as was observed in a family linked to FCD1. Finally,
      comparison of FCD1 and FCD2 exponential models suggested that the FCD1 phenotype
      is significantly more severe (P = 0.01). CONCLUSIONS: A combination of genetic
      mapping and retroillumination photography was used to quantify the severity of
      the disease phenotype associated with FCD2 and to compare it to the disease
      characteristics of FCD1. These data suggest that this approach might have
      sufficient resolution to discriminate between discrete genetic FCD backgrounds,
      which will potentially aid in patient management.

PMID- 20811065
TI  - Evaluation of the flexibility, efficacy, and safety of a foldable capsular
      vitreous body in the treatment of severe retinal detachment.
AB  - PURPOSE: To determine the flexibility, efficacy, and safety of a novel foldable
      capsular vitreous body (FCVB) in the treatment of severe retinal detachment in
      human eyes. METHODS: The study involved 11 patients with 11 severe retinal
      detachments. A standard three-port pars plana vitrectomy was performed, and the
      FCVB was triple-folded and implanted into the vitreous cavity. Balanced salt
      solution was then injected into the capsule of the FCVB to support the retina.
      The treated eyes were examined by ophthalmoscopy, fundus photography, and
      tonometry during a 3-month implantation period. B-scan ultrasonography, optical
      coherence tomography (OCT), ultrasound biomicroscopy (UBM), and electroretinogram
      (ERG) were also performed. The FCVB was removed and examined in the laboratory at
      the end of the 3-month treatment time. RESULTS: The FCVB was easily implanted
      into the vitreous cavity through a 3-mm incision and was easily removed through a
      2-mm scleral incision. Retinal reattachment was found in 8 (73%) of 11 eyes at
      the end of the 3-month treatment time. The fundus, B-scan, and OCT showed that
      the FCVB was well distributed in the vitreous cavity and evenly supported the
      retina. IOP and visual acuity in the FCVB-treated eyes did not show a significant
      difference when compared with the preoperative measurements. UBM showed that the
      FCVB smoothly contacted but did not crush the ciliary body. Laboratory
      examinations showed no significant inflammatory cells in the balanced salt
      solution, no decrease in spectral transmittance, and no blocking of tiny
      apertures from the FCVB after a 3-month implantation period. CONCLUSIONS: The
      FCVB was shown to be flexible, effective, and safe as a vitreous substitute over
      a 3-month implantation time. (ClinicalTrials.gov number, NCT00910702.).

PMID- 20811068
TI  - Evaluation of cannabinoid receptor 2 and metabotropic glutamate receptor 1
      functional responses using a cell impedance-based technology.
AB  - Recently, new technologies based on biosensors and called label free have been
      developed. These technologies eliminate the need for using markers and dyes. The
      authors applied one of these technologies, based on measurement of cell impedance
      variation, to study the pharmacological profiles of ligands for the cannabinoid
      receptor 2 (CB2), a Gi-coupled receptor, and for the metabopotropic glutamate
      receptor 1 (mGluR1), a Gq-coupled receptor. Reference agonists and
      antagonists/inverse agonists for the 2 receptors were applied to recombinant cell
      lines and impedance monitored over time. Agonists (JWH133 and CP55940 for CB2;
      quisqualate, glutamate, 1S-3R-ACPD, and S-3,5-DHPG for mGluR1) triggered a
      variation of impedance consistent in both potency and efficacy with data obtained
      using classical assays measuring cAMP or Ca(2+) levels. This effect was not
      present in the parental nontransfected cell line, confirming specific receptor
      mediated response. Application of antagonists (AM630 for CB2; YM298198,
      SCH1014222, J&J16259685, and CPCCOEt for mGluR1) reduced agonist-induced
      impedance changes. The only exception was the mGluR1 antagonist BAY367620 that,
      while active in the Ca(2+) assay, was inactive in the impedance assay. Overall,
      these results confirm the possibility of using cell impedance-based technology to
      study the pharmacological profile of ligands acting at G-protein-coupled
      receptors coupled to different downstream signaling pathways.

PMID- 20811066
TI  - Three gene-targeted mouse models of RNA splicing factor RP show late-onset RPE
      and retinal degeneration.
AB  - PURPOSE: Mutations in genes that produce proteins involved in mRNA splicing,
      including pre-mRNA processing factors 3, 8, and 31 (PRPF3, 8, and 31), RP9, and
      SNRNP200 are common causes of the late-onset inherited blinding disorder
      retinitis pigmentosa (RP). It is not known how mutations in these ubiquitously
      expressed genes lead to retina-specific disease. To investigate the pathogenesis
      of the RNA splicing factor forms of RP, the authors generated and characterized
      the retinal phenotypes of Prpf3-T494M, Prpf8-H2309P knockin mice. The retinal
      ultrastructure of Prpf31-knockout mice was also investigated. METHODS: The
      knockin mice have single codon alterations in their endogenous Prpf3 and Prpf8
      genes that mimic the most common disease causing mutations in human PRPF3 and
      PRPF8. The Prpf31-knockout mice mimic the null alleles that result from the
      majority of mutations identified in PRPF31 patients. The retinal phenotypes of
      the gene targeted mice were evaluated by electroretinography (ERG), light, and
      electron microscopy. RESULTS: The RPE cells of heterozygous Prpf3(+/T494M) and
      Prpf8(+/H2309P) knockin mice exhibited loss of the basal infoldings and
      vacuolization, with accumulation of amorphous deposits between the RPE and
      Bruch[b]'s membrane at age two years. These changes were more severe in the
      homozygous mice, and were associated with decreased rod function in the Prpf3
      T494M mice. Similar degenerative changes in the RPE were detected in Prpf31(+/-)
      mice at one year of age. CONCLUSIONS: The finding of similar degenerative changes
      in RPE cells of all three mouse models suggests that the RPE may be the primary
      cell type affected in the RNA splicing factor forms of RP. The relatively late
      onset phenotype observed in these mice is consistent with the typical adult onset
      of disease in patients with RP.

PMID- 20811069
TI  - Osteogenic potential of mandibular vs. long-bone marrow stromal cells.
AB  - Although fundamentally similar to other bones, the jaws demonstrate discrete
      responses to developmental, mechanical, and homeostatic regulatory signals. Here,
      we hypothesized that rat mandible vs. long-bone marrow-derived cells possess
      different osteogenic potential. We established a protocol for rat mandible and
      long-bone marrow stromal cell (BMSC) isolation and culture. Mandible BMSC
      cultures formed more colonies, suggesting an increased CFU-F population. Both
      mandible and long-bone BMSCs differentiated into osteoblasts. However, mandible
      BMSCs demonstrated augmented alkaline phosphatase activity, mineralization, and
      osteoblast gene expression. Importantly, upon implantation into nude mice,
      mandible BMSCs formed 70% larger bone nodules containing three-fold more
      mineralized bone compared with long-bone BMSCs. Analysis of these data
      demonstrates an increased osteogenic potential and augmented capacity of mandible
      BMSCs to induce bone formation in vitro and in vivo. Our findings support
      differences in the mechanisms underlying mandible homeostasis and the
      pathophysiology of diseases unique to the jaws.

PMID- 20811070
TI  - HEMA enhances IgG1 production by human B-cells in vitro.
AB  - We have previously shown that the resin monomer 2-hydroxyethylmethacrylate (HEMA)
      affects mouse B-lymphocyte activity, leading to increased IgG1 antibody
      production in vivo. In the present study, we tested, in vitro, the hypothesis
      that HEMA also affects human B-lymphocyte activity. The in vitro production of
      IgG1, IgM, and IgA in supernatants from purified human CD19+ B-lymphocyte
      cultures, containing different concentrations of HEMA, was assayed with ELISA.
      Proliferation was measured by [methyl-(3)H] thymidine incorporation. Of the
      different HEMA concentrations used, the lower concentrations caused a significant
      increase in IgG1 production, but not in IgM or IgA production, in vitro. The
      lower HEMA concentrations did not significantly change B-cell proliferation. At
      the highest concentration, HEMA significantly suppressed IgG1 and IgM production,
      as well as B-cell proliferation, in vitro. In conclusion, HEMA can, at certain
      concentrations, selectively enhance human B-lymphocyte IgG1 production.
      ABBREVIATIONS: 2-hydroxyethylmethacrylate (HEMA), Dulbecco's Modified Eagle's
      Medium supplemented with heat-inactivated fetal bovine serum, gentamycin,
      penicillin, and streptomycin (D-MEM++++), Enzyme-linked Immuno-sorbent Assay
      (ELISA), phosphate-buffered saline (PBS), ovalbumin (OVA), pokeweed mitogen
      (PWM), counts per minute (CPM).

PMID- 20811071
TI  - Effects of respiration on soft palate movement in feeding.
AB  - Cyclic soft palate elevation is temporally associated with masticatory jaw
      movement. However, the soft palate is normally lowered during nasal breathing to
      maintain retropalatal airway patency. We tested the hypothesis that the frequency
      and amplitude of soft palate elevation associated with mastication would be
      reduced during inspiration. Movements of radiopaque soft palate markers were
      recorded by videofluorography while 11 healthy volunteers ate solid foods.
      Breathing was monitored with plethysmography. Masticatory sequences were divided
      into processing and stage II transport cycles (food transport to the oropharynx
      before swallowing). In food processing, palatal elevation was less frequent and
      its displacement was smaller during inspiration than expiration. In stage II
      transport, the soft palate was elevated less frequently during inspiration than
      expiration. These findings suggest that masticatory soft palate movement is
      diminished during inspiration. The control of breathing appears to have a
      significant effect on soft palate elevation in mastication.

PMID- 20811072
TI  - Cost-saving tree-structured survival analysis for hip fracture of study of
      osteoporotic fractures data.
AB  - It is important to predict osteoporotic fracture risk accurately in order to
      select high-risk patients for treatment. Previous tree-structured survival
      analysis (TSSA) methods focused on optimization in statistical performance in
      construction of survival trees. However, they did not take into account the cost
      of the predictive variables. Because of the high cost of some predictors, the
      derived algorithm may have only limited application in practice. In this article,
      the authors consider the cost-effectiveness in TSSA and propose a cost-saving
      TSSA (denoted as CSTSSA) to construct the survival tree for identifying subjects
      at high risk of hip fracture based on the data from Study of Osteoporotic
      Fractures. The new rule is compared with the optimum classification based on log
      rank test statistics using the noninferiority test by Lu and others. The
      comparison results suggest that, for identifying patients at high risk of hip
      fracture, the CSTSSA is a good alternative to the optimum classification.

PMID- 20811073
TI  - Development of serum glycoproteomic profiling technique; simultaneous
      identification of glycosylation sites and site-specific quantification of glycan
      structure changes.
AB  - Characterization and interpretation of disease-associated alterations of protein
      glycosylation are the central aims of the emerging glycoproteomics projects,
      which are expected to lead to more sensitive and specific diagnosis and improve
      therapeutic outcomes for various diseases. Here we report a new approach to
      identify carbohydrate-targeting serum biomarkers, termed isotopic glycosidase
      elution and labeling on lectin-column chromatography (IGEL). This technology is
      based on glycan structure-specific enrichment of glycopeptides by lectin-column
      chromatography and site-directed tagging of N-glycosylation sites by (18)O during
      the elution with N-glycosidase. The combination of IGEL with 8-plex isobaric tag
      for relative and absolute quantitation (iTRAQ) stable isotope labeling enabled us
      not only to identify N-glycosylation sites effectively but also to compare glycan
      structures on each glycosylation site quantitatively in a single LC/MS/MS
      analysis. We applied this method to eight sera from lung cancer patients and
      controls, and finally identified 107 glycopeptides in their sera, including
      A2GL_Asn151, A2GL_Asn290, CD14_Asn132, CO8A_Asn417, C163A_Asn64, TIMP1_Asn30, and
      TSP1_Asn1049 which showed the significant change of the affinity to Concanavalin
      A (ConA) lectin between the lung cancer samples and the controls (p < 0.05 and
      more than twofold change). These screening results were further confirmed by the
      conventional lectin-column chromatography and immunoblot analysis using
      additional serum samples. Our novel methodology, which should be valuable for
      diverse biomarker discoveries, can provide high-throughput and quantitative
      profiling of glycan structure alterations.

PMID- 20811074
TI  - Quantitative proteomics and metabolomics analysis of normal human cerebrospinal
      fluid samples.
AB  - The analysis of cerebrospinal fluid (CSF) is used in biomarker discovery studies
      for various neurodegenerative central nervous system (CNS) disorders. However,
      little is known about variation of CSF proteins and metabolites between patients
      without neurological disorders. A baseline for a large number of CSF compounds
      appears to be lacking. To analyze the variation in CSF protein and metabolite
      abundances in a number of well-defined individual samples of patients undergoing
      routine, non-neurological surgical procedures, we determined the variation of
      various proteins and metabolites by multiple analytical platforms. A total of 126
      common proteins were assessed for biological variations between individuals by
      ESI-Orbitrap. A large spread in inter-individual variation was observed (relative
      standard deviations [RSDs] ranged from 18 to 148%) for proteins with both high
      abundance and low abundance. Technical variation was between 15 and 30% for all
      126 proteins. Metabolomics analysis was performed by means of GC-MS and nuclear
      magnetic resonance (NMR) imaging and amino acids were specifically analyzed by LC
      MS/MS, resulting in the detection of more than 100 metabolites. The variation in
      the metabolome appears to be much more limited compared with the proteome: the
      observed RSDs ranged from 12 to 70%. Technical variation was less than 20% for
      almost all metabolites. Consequently, an understanding of the biological
      variation of proteins and metabolites in CSF of neurologically normal individuals
      appears to be essential for reliable interpretation of biomarker discovery
      studies for CNS disorders because such results may be influenced by natural inter
      individual variations. Therefore, proteins and metabolites with high variation
      between individuals ought to be assessed with caution as candidate biomarkers
      because at least part of the difference observed between the diseased individuals
      and the controls will not be caused by the disease, but rather by the natural
      biological variation between individuals.

PMID- 20811075
TI  - Health-related quality of life differs between adolescent athletes and adolescent
      nonathletes.
AB  - CONTEXT: Patient-oriented outcome measures such as the Medical Outcomes Short
      Form (SF-36) and the Pediatric Outcomes Data Collection Instrument (PODCI) are
      important tools for determining the impact of events like sport-related injury on
      health-related quality of life (HRQoL). Unfortunately, there are no published
      studies using these instruments that compare adolescent athletes with their
      nonathlete peers, making interpretations of these measures in this population
      difficult. OBJECTIVE: To compare HRQoL in adolescent athletes and nonathletes
      using 2 common instruments. DESIGN: Cross-sectional. SETTING: 7 high schools.
      PARTICIPANTS: 219 athletes and 106 nonathletes. INTERVENTION: None. MAIN OUTCOME
      MEASURES: The SF-36 and the PODCI were completed in a counterbalanced manner
      during 1 session. Dependent variables included the 8 subscale and 2 composite
      scores of the SF-36 and the 5 subscale scores and 1 global score of the PODCI.
      RESULTS: On the SF-36, athletes reported higher scores on the physical function,
      general health, social functioning, and mental health subscales and the mental
      composite score and lower scores on the bodily pain subscale than nonathletes. On
      the PODCI, athletes reported higher scores on the sport and physical function and
      happiness subscales and lower scores on the pain/comfort subscale. CONCLUSIONS:
      Athletes reported higher scores on a number of SF-36 and PODCI subscales related
      to mental, emotional, and physical well-being than nonathletes. Our findings
      suggest that athletic involvement may be a benefit to the overall health status
      of adolescents and imply that athletes may be a distinct adolescent group
      requiring their own normative values when using the SF-36 and PODCI.

PMID- 20811076
TI  - Development of a measure of rehabilitation adherence for athletic training.
AB  - CONTEXT: Rehabilitation adherence is accepted as a critical component for
      attaining optimal outcomes. Poor adherence is recognized as a problem in the
      athletic training setting. Measurement has been inconsistent, and no measure has
      been developed for athletic training settings. OBJECTIVE: To identify indicators
      of sport-injury rehabilitation adherence relevant to athletic training and
      develop a Rehabilitation Adherence Measure for Athletic Training (RAdMAT) based
      on these indicators. DESIGN: Mixed methods, 3 steps. SETTING: College athletic
      training facility. PARTICIPANTS: Practicing certified athletic trainers (ATCs;
      n=7) generated items, experts (n=12) reviewed them, and practicing ATCs (n=164)
      completed the RAdMAT for their most, average, and least adherent athlete. MAIN
      OUTCOME MEASURE: RAdMAT. RESULTS: The RAdMAT is 16 items with 3 subscales.
      Subscales and total have good internal consistency and clearly discriminate among
      adherence levels. CONCLUSIONS: The RAdMAT is based on scholarly literature and
      clinical practice, making it particularly appropriate for use in athletic
      training clinical practice or for research purposes.

PMID- 20811077
TI  - Comparative effects of 6-week balance, gluteus medius strength, and combined
      programs on dynamic postural control.
AB  - CONTEXT: There are few outcomes-based studies that address hip strategy and
      gluteus medius strength (GMS) for maintaining dynamic postural control.
      OBJECTIVE: To determine whether GMS training, proprioception training, or a
      combination of the 2 has an effect on dynamic postural control. DESIGN: Pretest
      posttest, repeated measures. SETTING: Sports-medicine clinic. PARTICIPANTS: 48
      healthy male and female college students obtained via sample of convenience.
      INTERVENTIONS: Three 6-wk programs including exercises for proprioception, GMS,
      and combined. MAIN OUTCOMES MEASURES: Eight Star Excursion Balance Test (SEBT)
      reach distances and GMS for the dominant leg. RESULTS: There was no significant
      difference between groups. The combination group demonstrated the most
      improvements in SEBT reach distances, whereas the GMS group demonstrated the most
      improvement in GMS. CONCLUSION: Use of exercises for proprioception, GMS, or a
      combination of the 2 will help improve dynamic postural control in healthy,
      active individuals.

PMID- 20811078
TI  - The effect of plyometric training on peroneal latency.
AB  - CONTEXT: Peroneal reaction to sudden inversion has been determined to be too slow
      to overcome the joint motion. A focused plyometric training program may decrease
      the muscle's reaction time. OBJECTIVE: To determine the effect of a 6-wk
      plyometric training program on peroneus longus reaction time. DESIGN: Repeated
      measures. SETTING: University research laboratory. PARTICIPANTS: 48 healthy
      volunteers (age 20.0+/-1.2 y, height 176.1+/-16.9 cm, weight 74.5+/-27.9 kg) from
      a large Midwestern university. Subjects were randomly assigned to either a
      training group or a control group. INTERVENTIONS: Independent variables were
      group at 2 levels (training and no training) and time at 2 levels (pretest and
      posttest). The dependent variable was peroneal latency measured with surface
      electromyography. A custom-made trapdoor device capable of inverting the ankle to
      30 degrees was also used. Latency data were obtained from the time the trapdoor
      dropped until the peroneus longus muscle activated. Peroneal latency was measured
      before and after the 6-wk training period. The no-training group was instructed
      to maintain current activities. The training group performed a 6-wk plyometric
      protocol 3 times weekly. Data were examined with a repeated-measures ANOVA with 1
      within-subject factor (time at 2 levels) and 1 between-subjects factor (group at
      2 levels). A priori alpha level was set at P<or=.05. MAIN OUTCOME MEASURES:
      Pretest and posttest latency measurements (ms) were recorded for the peroneus
      longus muscle. RESULTS: The study found no significant group-by-time interaction
      (F1,46=0.03, P=.87). In addition, there was no difference between the pretest and
      posttest values (pretest=61.76+/-14.81 ms, posttest=59.24+/-12.28 ms; P=.18) and
      no difference between the training and no-training groups (training group=59.10+/
      12.18 ms, no-training group=61.79+/-15.18 ms; P=.43). CONCLUSIONS: Although
      latency measurements were consistent with previous studies, the plyometric
      training program did not cause significant change in the peroneus longus reaction
      time.

PMID- 20811079
TI  - Effects of saddle height, pedaling cadence, and workload on joint kinetics and
      kinematics during cycling.
AB  - CONTEXT: It is not clear how noncyclists control joint power and kinematics in
      different mechanical setups (saddle height, workload, and pedaling cadence).
      Joint mechanical work contribution and kinematics analysis could improve our
      comprehension of the coordinative pattern of noncyclists and provide evidence for
      bicycle setup to prevent injury. OBJECTIVE: To compare joint mechanical work
      distribution and kinematics at different saddle heights, workloads, and pedaling
      cadences. DESIGN: Quantitative experimental research based on repeated measures.
      SETTING: Research laboratory. PATIENTS: 9 healthy male participants 22 to 36
      years old without competitive cycling experience. INTERVENTION: Cycling on an
      ergometer in the following setups: 3 saddle heights (reference, 100% of
      trochanteric height; high, +3 cm; and low, -3 cm), 2 pedaling cadences (40 and 70
      rpm), and 3 workloads (0, 5, and 10 N of braking force). MAIN OUTCOME MEASURES:
      Joint kinematics, joint mechanical work, and mechanical work contribution of the
      joints. RESULTS: There was an increased contribution of the ankle joint (P=.04)
      to the total mechanical work with increasing saddle height (from low to high) and
      pedaling cadence (from 40 to 70 rpm, P<.01). Knee work contribution increased
      when saddle height was changed from high to low (P<.01). Ankle-, knee-, and hip
      joint kinematics were affected by saddle height changes (P<.01). CONCLUSIONS: At
      the high saddle position it could be inferred that the ankle joint compensated
      for the reduced knee-joint work contribution, which was probably effective for
      minimizing soft-tissue damage in the knee joint (eg, anterior cruciate ligament
      and patellofemoral cartilage). The increase in ankle work contribution and
      changes in joint kinematics associated with changes in pedaling cadence have been
      suggested to indicate poor pedaling-movement skill.

PMID- 20811080
TI  - Paraspinal muscle activity during symmetrical and asymmetrical weight training in
      idiopathic scoliosis.
AB  - CONTEXT: Various studies report decreased muscle activation in the concavity of
      the curve in patients with scoliosis. Such decreased muscle-performance capacity
      could lead to sustained postural deficits. OBJECTIVE: To investigate whether
      specific asymmetrical sports therapy exercises rather than symmetrical back
      strengthening can increase EMG amplitudes of paraspinal muscles in the concavity
      of the curve. DESIGN: Cross-sectional. SETTING: Laboratory. PARTICIPANTS: 16
      patients with idiopathic scoliosis. INTERVENTIONS: Patients performed 4 back
      strengthening exercises (front press, lat pull-down, roman chair, bent-over
      barbell row) during 1 test session. Each exercise was performed in a symmetrical
      and asymmetrical variant and repeated 3 times. MAIN OUTCOME MEASURE: EMG
      amplitudes of the paraspinal muscles were recorded in the thoracic and lumbar
      apexes of the scoliotic curve during each exercise. Ratios of convex- to concave
      side EMG activity were calculated. RESULTS: Statistical analysis revealed that
      the asymmetrical variants of front press at the lumbar level (P=.002) and roman
      chair and bent-over barbell row at the thoracic level (P<.0001, .001
      respectively) were superior in increasing EMG amplitudes in the concavity of the
      scoliotic curve. CONCLUSIONS: Specific asymmetrical exercises increase EMG
      amplitudes of paraspinal muscles in the concavity. If confirmed in longitudinal
      studies measuring improvements of postural deficits, these exercises may advance
      care of patients with scoliosis.

PMID- 20811081
TI  - Psycholinguistic changes in athletes' grief response to injury after written
      emotional disclosure.
AB  - CONTEXT: Grief can be a common psychological characteristic of long-term injury,
      but few athletes are taught how to effectively deal with these intense emotions.
      OBJECTIVE: To examine the effectiveness of Pennebaker's standard writing paradigm
      in improving athletes' psychological response to injury after engaging in written
      disclosure. DESIGN: Repeated-measures design with 6 data-collection time points.
      SETTING: Sport-injury clinics. PARTICIPANTS: 9 elite long-term-injured athletes.
      MEASURES AND INTERVENTION: Participants were administered the Psychological
      Responses to Sport Injury Inventory and the Rehabilitation Beliefs Survey at 3
      times preintervention and postintervention. Intervention comprised three 20-min
      writing sessions. Linguistic analyses were carried out using the Linguistic
      Inquiry Word Count to determine whether changes in word categories would be
      associated with postintervention changes in grief characteristics and
      rehabilitation-belief subscales. RESULTS: There were significant differences in
      athletes' grief characteristics postintervention, with athletes feeling less
      devastated, dispirited, cheated, and restless by their injury and increasing the
      reorganization of their thoughts. Corresponding evidence from text analyses
      further supported these changes, with athletes linguistically demonstrating that
      they were actively working through their grief-related response using improved
      cognitive processing (F2,16=5.15, P=.019, Eta2=.39) and the disinhibition of
      positive and negative affect (F2,16=4.05, P=.038, Eta2=.34). There were no
      significant changes in athletes' rehabilitation beliefs, which remained high
      throughout the testing period. CONCLUSIONS: Overall, the findings demonstrated
      that written emotional disclosure was effective in enhancing psychological
      rehabilitation by contributing to a greater personal understanding of the injury
      event and attenuating athletes' grief-related response.

PMID- 20811082
TI  - The effectiveness of electromyographic biofeedback supplementation during knee
      rehabilitation after injury.

PMID- 20811083
TI  - Special issue on the biomimetics of aquatic life: applications for engineering.

PMID- 20811084
TI  - Convergent evolution to an aptamer observed in small populations on DNA
      microarrays.
AB  - The development of aptamers on custom synthesized DNA microarrays, which has been
      demonstrated in recent publications, can facilitate detailed analyses of sequence
      and fitness relationships. Here we use the technique to observe the paths taken
      through sequence-fitness space by three different evolutionary regimes: asexual
      reproduction, recombination and model-based evolution. The different evolutionary
      runs are made on the same array chip in triplicate, each one starting from a
      small population initialized independently at random. When evolving to a common
      target protein, glucose-6-phosphate dehydrogenase (G6PD), these nine distinct
      evolutionary runs are observed to develop aptamers with high affinity and to
      converge on the same motif not present in any of the starting populations. Regime
      specific differences in the evolutions, such as speed of convergence, could also
      be observed.

PMID- 20811085
TI  - High-frequency and low-frequency effects on vibrational resonance in a synthetic
      gene network.
AB  - The high-frequency and low-frequency effects on vibrational resonance (VR) in a
      synthetic gene network are studied. Results show that the role of the high
      frequency signal in VR acts as that of noise in stochastic resonance (SR), namely
      a high-frequency signal can change the effective value of the control parameter
      such that the random state-state transitions of the switch can happen. A low
      frequency signal with lower frequency and higher amplitude tends to favor the
      response of the system. When VR occurs, the ratio of the optimal amplitude
      (B(opt)) to the corresponding frequency (Omega) of the high-frequency signal is a
      definite constant. Furthermore, if noise is introduced into the system, noise
      plays a suppressive role for VR, and various resonance phenomena including the
      bell-shaped VR and VR without tuning are exhibited in the system.

PMID- 20811086
TI  - A study on electrode gels for skin conductance measurements.
AB  - Low-frequency skin conductance is used within several clinical applications and
      is mainly sensitive to sweating and the moisture content of the stratum corneum,
      but also how electrodes introduce changes in the electrical properties. Four
      electrode gels were investigated with regard to sorption characteristics and
      electrical properties. Skin conductance time series were collected from 18 test
      subjects during relaxation, exercise and recovery, wearing different pairs of
      electrodes contralaterally on the hypothenar and the T9 dermatome. Pressure test
      was applied on the T9 electrodes. Impedance frequency sweeps were taken on the T9
      electrodes the same day and the next, parameterized to the Cole model. ANOVA on
      the initial skin conductance level change, exercise response amplitude, recovery
      offset and pressure-induced changes revealed significant differences among gel
      types. The wetter gels caused a higher positive level change, a greater response
      amplitude, larger recovery offset and greater pressure-induced artifacts compared
      to the solid gels. Sweating on the T9 site led to negative skin conductance
      responses for the wetter gels. Correlations were found between the desorption
      measurements and the initial skin conductance level change (hypothenar: R = 0.988
      T9: R = 0.901) RM-ANOVA on the Cole parameters revealed a significant decrease in
      R(s) of the most resistive gel. Clinical implications are discussed.

PMID- 20811087
TI  - TaserX26 current increases with dart depth.
AB  - The TaserX26 output current waveform consists of an arc phase and a stimulation
      phase, which is responsible for electromuscular stimulation. We modeled the
      current discharge during the stimulation phase using a simplified overdamped
      series R-L-C circuit. The model provides a reasonable approximation to the
      TaserX26 current waveform and explains the changes in the peak current and rise
      and fall time constants due to load variations. We simulated a physiological load
      using a 0.2% saline solution in a 75 * 30 * 17.2 cm fish tank to represent a
      supine human torso with resistivity similar to skeletal muscles. The peak current
      and load resistance varied more with the depth of the Taser darts in saline than
      with their distance of separation. Experiments performed on three pigs confirmed
      the decrease in resistance and increase in current with the depth of the Taser
      dart in the body. An R-C circuit with a time constant of about 2 ms was used to
      measure the variation of the Taser in stimulating cardiac cells. The Taser is
      2.05 times more likely to stimulate the cardiac cell when the darts penetrate 9
      mm into the load as compared to when they were just touching the load.

PMID- 20811088
TI  - Classification effects of real and imaginary movement selective attention tasks
      on a P300-based brain-computer interface.
AB  - Brain-computer interfaces (BCIs) rely on various electroencephalography
      methodologies that allow the user to convey their desired control to the machine.
      Common approaches include the use of event-related potentials (ERPs) such as the
      P300 and modulation of the beta and mu rhythms. All of these methods have their
      benefits and drawbacks. In this paper, three different selective attention tasks
      were tested in conjunction with a P300-based protocol (i.e. the standard counting
      of target stimuli as well as the conduction of real and imaginary movements in
      sync with the target stimuli). The three tasks were performed by a total of 10
      participants, with the majority (7 out of 10) of the participants having never
      before participated in imaginary movement BCI experiments. Channels and methods
      used were optimized for the P300 ERP and no sensory-motor rhythms were explicitly
      used. The classifier used was a simple Fisher's linear discriminant. Results were
      encouraging, showing that on average the imaginary movement achieved a P300
      versus No-P300 classification accuracy of 84.53%. In comparison, mental counting,
      the standard selective attention task used in previous studies, achieved 78.9%
      and real movement 90.3%. Furthermore, multiple trial classification results were
      recorded and compared, with real movement reaching 99.5% accuracy after four
      trials (12.8 s), imaginary movement reaching 99.5% accuracy after five trials (16
      s) and counting reaching 98.2% accuracy after ten trials (32 s).

PMID- 20811089
TI  - Restoration of segregated, physiological neuronal connectivity by desynchronizing
      stimulation.
AB  - The loss of segregation of neuronal signal processing pathways is an important
      hypothesis for explaining the origin of functional deficits as associated with
      Parkinson's disease. Here we use a modeling approach which is utilized to study
      the influence of deep brain stimulation on the restoration of segregated activity
      in the target structures. Besides the spontaneous activity of the target network,
      the model considers a weak sensory input mimicking signal processing tasks,
      electrical deep brain stimulation delivered through a standard DBS electrode and
      synaptic plasticity. We demonstrate that the sensory input is capable of inducing
      a modification of the network structure which results in segregated microcircuits
      if the network is initialized in the healthy, desynchronized state. Depending on
      the strength and coverage, the sensory input is capable of restoring the
      functional sub-circuits even if the network is initialized in the synchronized,
      pathological state. Weak coordinated reset stimulation, applied to a network
      featuring a loss of segregation caused by global synchronization, is able to
      restore the segregated activity and to truncate the pathological, synchronized
      activity.

PMID- 20811090
TI  - Inhibition of neuronal cell-cell adhesion measured by the microscopic aggregation
      assay and impedance sensing.
AB  - Microscopic aggregation assay and impedance sensing (IS) were used to monitor a
      change in in vitro neuron-neuron adhesion in response to blocking of cell
      adhesion molecules. By blocking neuron-neuron adhesion, migration and aggregation
      of neuronal cells can be inhibited. This leads to better control of spatial
      arrangement of cells in culture. In the literature N-CAM, L1 and N-cadherin
      proteins are pointed out as main regulators of neuronal adhesion. In this study,
      these three main cell adhesion molecules were used to inhibit neuron-to-neuron
      adhesion and aggregation. Both soluble extracellular domains and antigen
      antibodies were added to these adhesion molecules. They were investigated for
      their blocking ability in neuronal cultures. First, in a 96 h aggregation assay
      on a low-adhesive substrate, the effect of inhibition of the three proteins on
      aggregation of cortical neurons was investigated optically. Both L1 antibody and
      L1 protein had no effect on the degree of aggregation. An N-cadherin antibody
      however was shown to be effective in aggregation inhibition at concentrations of
      1 and 3 ug ml(-1). Up to 96 h no aggregation occurred. A similar effect was
      achieved by the N-cadherin protein, although less distinct. N-CAM blocking
      revealed no inhibition of aggregation. Second, results from IS corresponded to
      those of the aggregation assays. In these experiments neuron-neuron adhesion was
      also inhibited by blocking N-CAM L1 and N-cadherin. Cortical neurons were
      cultured in small wells containing circular 100 um diameter gold electrodes, so
      small changes in cell-cell interactions in monolayers of neurons could be
      monitored by IS. Impedances of neuron-covered electrodes were significantly lower
      in the presence of the N-cadherin antibody and protein at concentrations of 1, 3
      and 10 ug ml(-1), indicating a less profound binding between adjacent neurons.
      Results from the aggregation assays and impedance measurements demonstrate the
      applicability of blocking cell adhesion molecules for inhibition of cell-cell
      adhesion and aggregation.

PMID- 20811091
TI  - Design of a robust EMG sensing interface for pattern classification.
AB  - Electromyographic (EMG) pattern classification has been widely investigated for
      neural control of external devices in order to assist with movements of patients
      with motor deficits. Classification performance deteriorates due to inevitable
      disturbances to the sensor interface, which significantly challenges the clinical
      value of this technique. This study aimed to design a sensor fault detection
      (SFD) module in the sensor interface to provide reliable EMG pattern
      classification. This module monitored the recorded signals from individual EMG
      electrodes and performed a self-recovery strategy to recover the classification
      performance when one or more sensors were disturbed. To evaluate this design, we
      applied synthetic disturbances to EMG signals collected from leg muscles of able
      bodied subjects and a subject with a transfemoral amputation and compared the
      accuracies for classifying transitions between different locomotion modes with
      and without the SFD module. The results showed that the SFD module maintained
      classification performance when one signal was distorted and recovered about 20%
      of classification accuracy when four signals were distorted simultaneously. The
      method was simple to implement. Additionally, these outcomes were observed for
      all subjects, including the leg amputee, which implies the promise of the
      designed sensor interface for providing a reliable neural-machine interface for
      artificial legs.

PMID- 20811092
TI  - Documenting, modelling and exploiting P300 amplitude changes due to variable
      target delays in Donchin's speller.
AB  - The P300 is an endogenous event-related potential (ERP) that is naturally
      elicited by rare and significant external stimuli. P300s are used increasingly
      frequently in brain-computer interfaces (BCIs) because the users of ERP-based
      BCIs need no special training. However, P300 waves are hard to detect and,
      therefore, multiple target stimulus presentations are needed before an interface
      can make a reliable decision. While significant improvements have been made in
      the detection of P300s, no particular attention has been paid to the variability
      in shape and timing of P300 waves in BCIs. In this paper we start filling this
      gap by documenting, modelling and exploiting a modulation in the amplitude of
      P300s related to the number of non-targets preceding a target in a Donchin
      speller. The basic idea in our approach is to use an appropriately weighted
      average of the responses produced by a classifier during multiple stimulus
      presentations, instead of the traditional plain average. This makes it possible
      to weigh more heavily events that are likely to be more informative, thereby
      increasing the accuracy of classification. The optimal weights are determined
      through a mathematical model that precisely estimates the accuracy of our speller
      as well as the expected performance improvement w.r.t. the traditional approach.
      Tests with two independent datasets show that our approach provides a marked
      statistically significant improvement in accuracy over the top-performing
      algorithm presented in the literature to date. The method and the theoretical
      models we propose are general and can easily be used in other P300-based BCIs
      with minimal changes.

PMID- 20811095
TI  - Scaffold engineering: a bridge to where?
AB  - A significant amount of federal research funding (over $4 billion) has gone into
      tissue engineering over the last 20 years. This has led to an exponential
      increase in research productivity as evidenced by the number of published papers
      referencing 'tissue engineering' and 'scaffold'. However, the number of tissue
      engineering products resulting from this research remains a paltry few, of which
      true tissue engineering products can be counted using the fingers of two hands.
      The fundamental question remains 'Why does such a gap exist between research and
      translation?'. This paper argues that such a gap exists in part due to the
      research paradigms followed in tissue engineering, in which a linear model is
      followed that assumed individual technical discovery can be bundled into model
      tissue engineering systems, followed by manufacturing scale up and regulatory
      approval. As such, most research funding follows this linear model with the vast
      majority of research spent on the discovery phase. This includes funding on both
      cell therapy and scaffold materials and engineering. It is assumed that therapy
      systems can readily be constructed by combining disparate technologies derived in
      different laboratories and that these therapies can readily achieve regulatory
      approval. Yet, most tissue engineering technologies fail to make it to clinical
      application because they simply have not been engineered for these specific
      applications or cannot be scaled to clinical level production. This paper argues
      that a different research paradigm is needed, essentially that of Pasteur's
      Quadrant proposed by Donald Stokes in the book of the same name. In this
      paradigm, research is pursued from the twin perspective of end use and the need
      for fundamental understanding. From this perspective, more funding emphasis
      should be placed on scalable manufacturing of systems that are designed for
      specific clinical applications that can attain regulatory approval. Funding of
      such scaffold/cell manufacturing technologies would not only enable greater
      translation of technology to clinical application, but would also enable a richer
      investigation of basic science issues. For example, the investigation of stem
      cell biology and differentiation in controlled 3D environments instead of 2D
      culture dishes. In this sense, a concentration of scaffold manufacturing would
      enable a quicker bridge across the 'Valley of Death' by providing for faster
      regulatory approval as stand alone products that would pave the way to
      combination products. At the same time, such manufacturing capabilities would
      broaden the scientific horizons in cell therapy.

PMID- 20811093
TI  - Decoding spoken words using local field potentials recorded from the cortical
      surface.
AB  - Pathological conditions such as amyotrophic lateral sclerosis or damage to the
      brainstem can leave patients severely paralyzed but fully aware, in a condition
      known as 'locked-in syndrome'. Communication in this state is often reduced to
      selecting individual letters or words by arduous residual movements. More
      intuitive and rapid communication may be restored by directly interfacing with
      language areas of the cerebral cortex. We used a grid of closely spaced,
      nonpenetrating micro-electrodes to record local field potentials (LFPs) from the
      surface of face motor cortex and Wernicke's area. From these LFPs we were
      successful in classifying a small set of words on a trial-by-trial basis at
      levels well above chance. We found that the pattern of electrodes with the
      highest accuracy changed for each word, which supports the idea that closely
      spaced micro-electrodes are capable of capturing neural signals from independent
      neural processing assemblies. These results further support using cortical
      surface potentials (electrocorticography) in brain-computer interfaces. These
      results also show that LFPs recorded from the cortical surface (micro
      electrocorticography) of language areas can be used to classify speech-related
      cortical rhythms and potentially restore communication to locked-in patients.

PMID- 20811096
TI  - Electrospun nanofiber meshes with tailored architectures and patterns as
      potential tissue-engineering scaffolds.
AB  - Using a stainless steel mesh as a template collector, electrospun nanofiber
      meshes with well-tailored architectures and patterns were successfully prepared
      from biodegradable poly (epsilon-caprolactone) (PCL). It was found that the
      resulting PCL nanofiber (NF) meshes had similar topological structures to that of
      the template stainless steel mesh. Such PCL nanofiber meshes (NF meshes) had
      improved the tensile strength with Young's modulus of 62.7 +/- 5.3 MPa, which is
      >40% higher than the modulus of 44 +/- 5.7 MPa as measured with the corresponding
      randomly oriented PCL nanofiber mats (RNF mat). On the other hand, the ultimate
      strain (87.30%) of the PCL NF meshes was distinctly lower than that of the PCL
      RNF mats (146.46%). To the best of our knowledge, this is the first time that the
      mechanical properties of nanofiber meshes with tailored architectures and
      patterns were studied and reported. When cultured with a mouse osteoblastic cell
      line (MC3T3-E1), the electrospun PCL NF meshes gave a much higher proliferation
      rate as compared with the randomly oriented PCL RNF mats. More importantly, it
      was found that the cells grew and elongated along the fiber orientation
      directions, and the resulted cellular organization and distribution mimicked the
      topological structures of the PCL NF meshes. These results indicated that the
      electrospun nanofiber scaffolds with tailored architectures and patterns hold
      potential for engineering functional tissues or organs, where an ordered cellular
      organization is essential.

PMID- 20811097
TI  - Cell adhesion and proliferation evaluation of SFF-based biodegradable scaffolds
      fabricated using a multi-head deposition system.
AB  - Scaffolds composed of biodegradable polymers and biocompatible ceramics are being
      used as substitutes for tissue engineering. In the development of such
      techniques, scaffolds with a controllable pore size and porosity were
      manufactured using solid free-form fabrication (SFF) methods to investigate the
      effects of cell interactions such as cell proliferation and differentiation. In
      this study, we describe the adhesion of human bone marrow stromal cells (hBMSCs)
      and proliferation characteristics of various scaffolds, which consist of
      biodegradable materials, fabricated using a multi-head deposition system (MHDS)
      that we developed. The MHDS uses novel technology that enables the production of
      three-dimensional (3D) microstructures. Fabrication of 3D tissue engineering
      scaffolds using the MHDS requires the combination of several technologies, such
      as motion control, thermal control, pneumatic control and computer-aided
      design/computer-assisted manufacturing software. The effects of a polymer and
      ceramic on a tissue scaffold were evaluated through mechanical testing and cell
      interaction analysis of various kinds of scaffolds fabricated using
      polycaprolactone, poly-lactic-co-glycolic acid and tri-calcium phosphate for bone
      regeneration applications. Based on these results, the feasibility of application
      to the tissue engineering of SFF-based 3D scaffolds fabricated by the MHDS was
      demonstrated.

PMID- 20811098
TI  - Precision extruding deposition (PED) fabrication of polycaprolactone (PCL)
      scaffolds for bone tissue engineering.
AB  - Bone tissue engineering is an emerging field providing viable substitutes for
      bone regeneration. Recent advances have allowed scientists and engineers to
      develop scaffolds for guided bone growth. However, success requires scaffolds to
      have specific macroscopic geometries and internal architectures conducive to
      biological and biophysical functions. Freeform fabrication provides an effective
      process tool to manufacture three-dimensional porous scaffolds with complex
      shapes and designed properties. A novel precision extruding deposition (PED)
      technique was developed to fabricate polycaprolactone (PCL) scaffolds. It was
      possible to manufacture scaffolds with a controlled pore size of 350 microm with
      designed structural orientations using this method. The scaffold morphology,
      internal micro-architecture and mechanical properties were evaluated using
      scanning electron microscopy (SEM), micro-computed tomography (micro-CT) and
      mechanical testing, respectively. An in vitro cell-scaffold interaction study was
      carried out using primary fetal bovine osteoblasts. Specifically, the cell
      proliferation and differentiation was evaluated by Alamar Blue assay for cell
      metabolic activity, alkaline phosphatase activity and osteoblast production of
      calcium. An in vivo study was performed on nude mice to determine the capability
      of osteoblast-seeded PCL to induce osteogenesis. Each scaffold was implanted
      subcutaneously in nude mice and, following sacrifice, was explanted at one of a
      series of time intervals. The explants were then evaluated histologically for
      possible areas of osseointegration. Microscopy and radiological examination
      showed multiple areas of osseous ingrowth suggesting that the osteoblast-seeded
      PCL scaffolds evoke osteogenesis in vivo. These studies demonstrated the
      viability of the PED process to fabricate PCL scaffolds having the necessary
      mechanical properties, structural integrity, and controlled pore size and
      interconnectivity desired for bone tissue engineering.

PMID- 20811099
TI  - Biofabrication: a 21st century manufacturing paradigm.
AB  - Biofabrication can be defined as the production of complex living and non-living
      biological products from raw materials such as living cells, molecules,
      extracellular matrices, and biomaterials. Cell and developmental biology,
      biomaterials science, and mechanical engineering are the main disciplines
      contributing to the emergence of biofabrication technology. The industrial
      potential of biofabrication technology is far beyond the traditional medically
      oriented tissue engineering and organ printing and, in the short term, it is
      essential for developing potentially highly predictive human cell- and tissue
      based technologies for drug discovery, drug toxicity, environmental toxicology
      assays, and complex in vitro models of human development and diseases. In the
      long term, biofabrication can also contribute to the development of novel
      biotechnologies for sustainable energy production in the future biofuel industry
      and dramatically transform traditional animal-based agriculture by inventing
      'animal-free' food, leather, and fur products. Thus, the broad spectrum of
      potential applications and rapidly growing arsenal of biofabrication methods
      strongly suggests that biofabrication can become a dominant technological
      platform and new paradigm for 21st century manufacturing. The main objectives of
      this review are defining biofabrication, outlining the most essential disciplines
      critical for emergence of this field, analysis of the evolving arsenal of
      biofabrication technologies and their potential practical applications, as well
      as a discussion of the common challenges being faced by biofabrication
      technologies, and the necessary conditions for the development of a global
      biofabrication research community and commercially successful biofabrication
      industry.

PMID- 20811100
TI  - Cell sheet technology and cell patterning for biofabrication.
AB  - We have developed cell sheet technology as a modern method for the fabrication of
      functional tissue-like and organ-like structures. This technology allows for a
      sheet of interconnected cells and cells in full contact with their natural
      extracellular environment to be obtained. A cell sheet can be patterned and
      composed according to more than one cell type. The key technology of cell sheet
      engineering is that a fabricated cell sheet can be harvested and transplanted
      utilizing temperature-responsive surfaces. In this review, we summarize different
      aspects of cell sheet engineering and provide a survey of the application of cell
      sheets as a suitable material for biofabrication and clinics. Moreover, since
      cell micropatterning is a key tool for cell sheet engineering, in this review we
      focus on the introduction of our approaches to cell micropatterning and cell co
      culture to the principles of automation and how they can be subjected to easy
      robotics programming. Finally, efforts towards making cell sheet technology
      suitable for biofabrication and robotic biofabrication are also summarized.

PMID- 20811101
TI  - A hybrid biomimetic scaffold composed of electrospun polycaprolactone nanofibers
      and self-assembled peptide amphiphile nanofibers.
AB  - Nanofibrous electrospun poly (epsilon-caprolactone) (ePCL) scaffolds have
      inherent structural advantages, but lack of bioactivity has limited their
      usefulness in biomedical applications. Thus, here we report the development of a
      hybrid, nanostructured, extracellular matrix (ECM) mimicking scaffold by a
      combination of ePCL nanofibers and self-assembled peptide amphiphile (PA)
      nanofibers. The PAs have ECM mimicking characteristics including a cell adhesive
      ligand (RGDS) and matrix metalloproteinase-2 (MMP-2) mediated degradable sites.
      Transmission electron microscope imaging verified successful PA self-assembly
      into nanofibers (diameters of 8-10 nm) using a solvent evaporation method. This
      evaporation method was then used to successfully coat PAs onto ePCL nanofibers
      (diameters of 300-400 nm), to develop hybrid, bioactive scaffolds. Scanning
      electron microscope characterization showed that the PA coatings did not
      interfere with the porous ePCL nanofiber network. Human mesenchymal stem cells
      (hMSCs) were seeded onto the hybrid scaffolds to evaluate their bioactivity.
      Significantly greater attachment and spreading of hMSCs were observed on ePCL
      nanofibers coated with PA-RGDS as compared to ePCL nanofibers coated with PA-S
      (no cell adhesive ligand) and uncoated ePCL nanofibers. Overall, this novel
      strategy presents a new solution to overcome the current bioactivity challenges
      of electrospun scaffolds and combines the unique characteristics of ePCL
      nanofibers and self-assembled PA nanofibers to provide an ECM mimicking
      environment. This has great potential to be applied to many different electrospun
      scaffolds for various biomedical applications.

PMID- 20811102
TI  - Fabrication of platinum nanopillars on peptide-based soft structures using a
      focused ion beam.
AB  - An expedient entry into the construction of bionanocomposites by merging peptide
      self-assembly, focused ion beam milling, and electron beam-induced deposition is
      described. Hexapeptides 1 and 2 revealed spherical self-assembled structures
      which are confirmed by a scanning electron microscope (SEM), atomic force
      microscope (AFM), focused ion beam/high-resolution scanning electron microscope
      (FIB-HRSEM), and high-resolution transmission electron microscopy (HRTEM). The
      microspheres from 1 and 2 are milled with the help of an ion beam to create
      different shapes. Soft spherical peptide-based structures were also subjected to
      fabrication under a gallium ion beam, followed by deposition of platinum pillars
      through a direct write process. It is envisaged that such hybrid
      bionanocomposites could have applications ranging from Pt-based hydrogenation
      catalysts to bioelectronics. In addition, such a fabrication process might also
      be useful to electrically connect two biological systems in order to study an
      electrical signal or electron transport phenomenon and structural
      transformations.

PMID- 20811103
TI  - Fabrication of a two-level tumor bone repair biomaterial based on a rapid
      prototyping technique.
AB  - After the removal of the giant cell tumor (GCT) of bone, it is necessary to fill
      the defects with adequate biomaterials. A new functional bone repair material
      with both stimulating osteoblast growth and inhibiting osteoclast activity has
      been developed with phosphorylated chitosan (P-chitosan) and disodium (1 --> 4)-2
      deoxy-2-sulfoamino-beta-D-glucopyranuronan (S-chitosan) as the additives of
      poly(lactic acid-co-glycolic acid) (PLGA)/calcium phosphate (TCP) scaffolds based
      on a double-nozzle low-temperature deposition manufacturing technique. A computer
      assisted design model was used and the optimal fabrication parameters were
      determined through the manipulation of a pure PLGA/TCP system. The microscopic
      structures, water absorbability and mechanical properties of the samples with
      different P-chitosan and S-chitosan concentrations were characterized
      correspondingly. The results suggested that this unique composite porous scaffold
      material is a potential candidate for the repair of large bone defects after a
      surgical removal of GCT.

PMID- 20811104
TI  - A brief review of dispensing-based rapid prototyping techniques in tissue
      scaffold fabrication: role of modeling on scaffold properties prediction.
AB  - Artificial scaffolds play vital roles in tissue engineering as they provide a
      supportive environment for cell attachment, proliferation and differentiation
      during tissue formation. Fabrication of tissue scaffolds is thus of fundamental
      importance for tissue engineering. Of the variety of scaffold fabrication
      techniques available, rapid prototyping (RP) methods have attracted a great deal
      of attention in recent years. This method can improve conventional scaffold
      fabrication by controlling scaffold microstructure, incorporating cells into
      scaffolds and regulating cell distribution. All of these contribute towards the
      ultimate goal of tissue engineering: functional tissues or organs. Dispensing is
      typically used in different RP techniques to implement the layer-by-layer
      fabrication process. This article reviews RP methods in tissue scaffold
      fabrication, with emphasis on dispensing-based techniques, and analyzes the
      effects of different process factors on fabrication performance, including flow
      rate, pore size and porosity, and mechanical cell damage that can occur in the
      bio-manufacturing process.

PMID- 20811105
TI  - Fabrication and characterization of bio-engineered cardiac pseudo tissues.
AB  - We report on fabricating functional three-dimensional (3D) tissue constructs
      using an inkjet based bio-prototyping method. With the use of modified inkjet
      printers, contractile cardiac hybrids that exhibit the forms of the 3D
      rectangular sheet and even the 'half heart' (with two connected ventricles) have
      been fabricated by arranging alternate layers of biocompatible alginate hydrogels
      and mammalian cardiac cells according to pre-designed 3D patterns. In this study,
      primary feline adult and H1 cardiomyocytes were used as model cardiac cells.
      Alginate hydrogels with controlled micro-shell structures were built by spraying
      cross-linkers in micro-drops onto un-gelled alginic acid. The cells remained
      viable in constructs as thick as 1 cm due to the programmed porosity. Microscopic
      and macroscopic contractile functions of these cardiomyocyte constructs were
      observed in vitro. These results suggest that the inkjet bio-prototyping method
      could be used for hierarchical design of functional cardiac pseudo tissues,
      balanced with porosity for mass transport and structural support.

PMID- 20811106
TI  - Computer-aided design of microvasculature systems for use in vascular scaffold
      production.
AB  - In vitro biomedical engineering of intact, functional vascular networks, which
      include capillary structures, is a prerequisite for adequate vascular scaffold
      production. Capillary structures are necessary since they provide the elements
      and compounds for the growth, function and maintenance of 3D tissue structures.
      Computer-aided modeling of stereolithographic (STL) micro-computer tomographic
      (micro-CT) 3D models is a technique that enables us to mimic the design of
      vascular tree systems containing capillary beds, found in tissues. In our first
      paper (Mondy et al 2009 Tissue Eng. at press), using micro-CT, we studied the
      possibility of using vascular tissues to produce data capable of aiding the
      design of vascular tree scaffolding, which would help in the reverse engineering
      of a complete vascular tree system including capillary bed structures. In this
      paper, we used STL models of large datasets of computer-aided design (CAD) data
      of vascular structures which contained capillary structures that mimic those in
      the dermal layers of rabbit skin. Using CAD software we created from 3D STL
      models a bio-CAD design for the development of capillary-containing vascular tree
      scaffolding for skin. This method is designed to enhance a variety of therapeutic
      protocols including, but not limited to, organ and tissue repair, systemic
      disease mediation and cell/tissue transplantation therapy. Our successful
      approach to in vitro vasculogenesis will allow the bioengineering of various
      other types of 3D tissue structures, and as such greatly expands the potential
      applications of biomedical engineering technology into the fields of biomedical
      research and medicine.

PMID- 20811107
TI  - The role of printing parameters and scaffold biopolymer properties in the
      efficacy of a new hybrid nano-bioprinting system.
AB  - We created a hybrid nano-bioprinting system, which combines the initial
      patterning capabilities of direct cell writing with the active patterning
      capabilities of superparamagnetic nanoparticles. Biofabrication conditions,
      including printing parameters and scaffold biopolymer properties, may affect cell
      viability, nanoparticle manipulation and patterning capabilities. Nanoparticles
      were printed under varied conditions either in the biopolymer or loaded inside
      cells. Cell viability, alginate viscosity, nanoparticle movement and printing
      resolution were measured. We now show that while nanoparticles decreased cell
      viability, nozzle size had no significant effect. High printing pressure
      decreased cell viability, but viability loss was not accentuated by
      nanoparticles. High nanoparticle concentrations increased alginate viscosity at
      higher alginate concentrations. Nanoparticle velocity in response to a magnetic
      field was a function of nanoparticle diameter and scaffold viscosity, which
      agreed with a mathematical model of nanoparticle movement. Finally, the nano
      bioprinting system resolution and patterning precision were not affected by
      nanoparticles in the prepolymer solution. These data suggest that nanoparticle
      incorporation in solid freeform fabrication does not change biofabrication
      parameters unless high nanoparticle concentrations are used. Future work includes
      developing vascularized tissue engineering constructs using the nano-bioprinting
      system.

PMID- 20811109
TI  - Axisymmetric polydimethysiloxane microchannels for in vitro hemodynamic studies.
AB  - The current microdevices used for biomedical research are often manufactured
      using microelectromechanical systems (MEMS) technology. Although it is possible
      to fabricate precise and reproducible rectangular microchannels using soft
      lithography techniques, this kind of geometry may not reflect the actual
      physiology of the microcirculation. Here, we present a simple method to fabricate
      circular polydimethysiloxane (PDMS) microchannels aiming to mimic an in vivo
      microvascular environment and suitable for state-of-the-art microscale flow
      visualization techniques, such as confocal microPIV/PTV. By using a confocal
      microPTV system individual red blood cells (RBCs) were successfully tracked
      trough a 75 microm circular PDMS microchannel. The results show that RBC lateral
      dispersion increases with the volume fraction of RBCs in the solution, i.e. with
      the hematocrit.

PMID- 20811108
TI  - Coating of hydrophobins on three-dimensional electrospun poly(lactic-co-glycolic
      acid) scaffolds for cell adhesion.
AB  - Surface modification with hydrophobins is very important for cell adhesion in its
      applications in biosensor fabrication. In this study, we modified the surface of
      three-dimensional electrospun poly(lactide-co-glycolide) (PLGA) scaffolds with
      hydrophobin HFBI and collagen, and investigated its applications for cell
      adhesion. We found that HFBI could not only improve the hydrophilicity of the
      three-dimensional electrospun PLGA scaffolds but also endow the electrospun PLGA
      scaffolds with water permeability. This permeability should be attributed to both
      the hydrophilicity of the modified PLGA surface and the large positive capillary
      effect induced by the microstructures. Further experiment indicated that HFBI
      modification could improve collagen immobilization on the electrospun PLGA
      scaffolds and the HFBI/collagen modified electrospun PLGA scaffolds showed higher
      efficiency in promoting cell adhesion than the native PLGA scaffolds. This
      finding should be of potential application in biosensor device fabrication.

PMID- 20811110
TI  - Digital fabrication of multi-material biomedical objects.
AB  - This paper describes a multi-material virtual prototyping (MMVP) system for
      modelling and digital fabrication of discrete and functionally graded multi
      material objects for biomedical applications. The MMVP system consists of a DMMVP
      module, an FGMVP module and a virtual reality (VR) simulation module. The DMMVP
      module is used to model discrete multi-material (DMM) objects, while the FGMVP
      module is for functionally graded multi-material (FGM) objects. The VR simulation
      module integrates these two modules to perform digital fabrication of multi
      material objects, which can be subsequently visualized and analysed in a virtual
      environment to optimize MMLM processes for fabrication of product prototypes.
      Using the MMVP system, two biomedical objects, including a DMM human spine and an
      FGM intervertebral disc spacer are modelled and digitally fabricated for
      visualization and analysis in a VR environment. These studies show that the MMVP
      system is a practical tool for modelling, visualization, and subsequent
      fabrication of biomedical objects of discrete and functionally graded multi
      materials for biomedical applications. The system may be adapted to control MMLM
      machines with appropriate hardware for physical fabrication of biomedical
      objects.

PMID- 20811111
TI  - A phase diagram for microfabrication of geometrically controlled hydrogel
      scaffolds.
AB  - Hydrogels are considered as excellent candidates for tissue substitutes by virtue
      of their high water content and biphasic nature. However, the fact that they are
      soft, wet and floppy renders them difficult to process and use as custom-designed
      scaffolds. To address this problem alginate hydrogels were modeled and
      characterized by measuring stress-strain and creep behavior as well as viscosity
      as a function of sodium alginate concentration, cross-linking time and calcium
      ion concentration. The gels were then microfabricated into scaffolds using the
      pressure-assisted microsyringe. The mechanical and viscous characteristics were
      used to generate a processing window in the form of a phase diagram which
      describes the fidelity of the scaffolds as a function of the material and machine
      parameters. The approach can be applied to a variety of microfabrication methods
      and biomaterials in order to design well-controlled custom scaffolds.

PMID- 20811112
TI  - Laser-based patterning for transfected cell microarrays.
AB  - The spatial control over biomolecule- and cell-surface interactions is of great
      interest to a broad range of biomedical applications, including sensors,
      implantable devices and cell microarrays. Microarrays in particular require
      precise spatial control and the formation of patterns with microscale features.
      Here, we have developed an approach specifically designed for transfected cell
      microarray (TCM) applications that allows microscale spatial control over the
      location of both DNA and cells on highly doped p-type silicon substrates. This
      was achieved by surface modification, involving plasma polymerization of
      allylamine, grafting of poly(ethylene glycol) and subsequent excimer laser
      ablation. DNA could be delivered in a spatially defined manner using ink-jet
      printing. In addition, electroporation was investigated as an approach to
      transfect attached cells with adsorbed DNA and good transfection efficiencies of
      approximately 20% were observed. The ability of the microstructured surfaces to
      spatially direct both DNA adsorption and cell attachment was demonstrated in a
      functional TCM, making this system an exciting platform for chip-based functional
      genomics.

PMID- 20811113
TI  - A Lindenmayer system-based approach for the design of nutrient delivery networks
      in tissue constructs.
AB  - Large thick tissue constructs have reported limited success primarily due to the
      inability of cells to survive deep within the scaffold. Without access to
      adequate nutrients, cells placed deep within the tissue construct will die out,
      leading to non-uniform tissue regeneration. Currently, there is a necessity to
      design nutrient conduit networks within the tissue construct to enable cells to
      survive in the matrix. However, the design of complex networks within a tissue
      construct is challenging. In this paper, we present the Lindenmayer system, an
      elegant fractal-based language algorithm framework, to generate conduit networks
      in two- and three-dimensional architecture with several degrees of complexity.
      The conduit network maintains a parent-child relationship between each branch of
      the network. Several L-system parameters have been studied-branching angle,
      branch length, ratio of parent to child branch diameter, etc-to simulate several
      architectures under a given L-system notation. We have also presented a layered
      manufacturing-based UV-photopolymerization process using the Texas Instruments
      DLP system to fabricate the branched structures. This preliminary work showcases
      the applicability of L-system-based construct designs to drive scaffold
      fabrication systems.

PMID- 20811114
TI  - Characterization of the flow behavior of alginate/hydroxyapatite mixtures for
      tissue scaffold fabrication.
AB  - Mixtures of alginate and hydroxyapatite (HA) are promising materials for
      biomedical applications such as the fabrication of tissue scaffolds. In this
      paper, the flow behavior of alginate/HA mixtures was investigated and determined
      to be dependent on the concentration of both alginate and HA, and temperature.
      The relationships were mathematically established and verified with experimental
      results. As applied to the tissue scaffold fabrication, the flow rate of the
      biomaterial solution was predicted from the established flow behavior and
      verified by experiments. On this basis, the moving speed of the needle was
      determined and used in the tissue scaffold fabrication. The results obtained show
      that the knowledge of the flow behavior is essential to the fabrication of tissue
      scaffolds with an interconnected microstructure.

PMID- 20811115
TI  - Bioprinting is coming of age: Report from the International Conference on
      Bioprinting and Biofabrication in Bordeaux (3B'09).
AB  - The International Conference on Bioprinting and Biofabrication in Bordeaux
      (3B'09) demonstrated that the field of bioprinting and biofabrication continues
      to evolve. The increasing number and broadening geography of participants, the
      emergence of new exciting bioprinting technologies, and the attraction of young
      investigators indicates the strong growth potential of this emerging field.
      Bioprinting can be defined as the use of computer-aided transfer processes for
      patterning and assembling living and non-living materials with a prescribed 2D or
      3D organization in order to produce bio-engineered structures serving in
      regenerative medicine, pharmacokinetic and basic cell biology studies. The use of
      bioprinting technology for biofabrication of in vitro assay has been shown to be
      a realistic short-term application. At the same time, the principal feasibility
      of bioprinting vascularized human organs as well as in vivo bioprinting has been
      demonstrated. The bioprinting of complex 3D human tissues and constructs in vitro
      and especially in vivo are exciting, but long-term, applications. It was decided
      that the 5th International Conference on Bioprinting and Biofabrication would be
      held in Philadelphia, USA in October 2010. The specially appointed 'Eploratory
      Committee' will consider the possibility of turning the growing bioprinting
      community into a more organized entity by creating a new bioprinting and
      biofabrication society. The new journal Biofabrication was also presented at
      3B'09. This is an important milestone per se which provides additional objective
      evidence that the bioprinting and biofabrication field is consolidating and
      maturing. Thus, it is safe to state that bioprinting technology is coming of age.

PMID- 20811116
TI  - In vivo bioprinting for computer- and robotic-assisted medical intervention:
      preliminary study in mice.
AB  - We present the first attempt to apply bioprinting technologies in the perspective
      of computer-assisted medical interventions. A workstation dedicated to high
      throughput biological laser printing has been designed. Nano-hydroxyapatite (n
      HA) was printed in the mouse calvaria defect model in vivo. Critical size bone
      defects were performed in OF-1 male mice calvaria with a 4 mm diameter trephine.
      Prior to laser printing experiments, the absence of inflammation due to laser
      irradiation onto mice dura mater was shown by means of magnetic resonance
      imaging. Procedures for in vivo bioprinting and results obtained using
      decalcified sections and x-ray microtomography are discussed. Although
      heterogeneous, these preliminary results demonstrate that in vivo bioprinting is
      possible. Bioprinting may prove to be helpful in the future for medical robotics
      and computer-assisted medical interventions.

PMID- 20811117
TI  - Combining electrospinning and fused deposition modeling for the fabrication of a
      hybrid vascular graft.
AB  - Tissue engineering of blood vessels is a promising strategy in regenerative
      medicine with a broad spectrum of potential applications. However, many hurdles
      for tissue-engineered vascular grafts, such as poor mechanical properties,
      thrombogenicity and cell over-growth inside the construct, need to be overcome
      prior to the clinical application. To surmount these shortcomings, we developed a
      poly-L-lactide (PLLA)/poly-epsilon-caprolactone (PCL) scaffold releasing heparin
      by a combination of electrospinning and fused deposition modeling technique.
      PLLA/heparin scaffolds were produced by electrospinning in tubular shape and then
      fused deposition modeling was used to armor the tube with a single coil of PCL on
      the outer layer to improve mechanical properties. Scaffolds were then seeded with
      human mesenchymal stem cells (hMSCs) and assayed in terms of morphology,
      mechanical tensile strength, cell viability and differentiation. This particular
      scaffold design allowed the generation of both a drug delivery system amenable to
      surmount thrombogenic issues and a microenvironment able to induce endothelial
      differentiation. At the same time, the PCL external coiling improved mechanical
      resistance of the microfibrous scaffold. By the combination of two notable
      techniques in biofabrication--electrospinning and FDM--and exploiting the
      biological effects of heparin, we developed an ad hoc differentiating device for
      hMSCs seeding, able to induce differentiation into vascular endothelium.

PMID- 20811118
TI  - Bioprinting by laser-induced forward transfer for tissue engineering
      applications: jet formation modeling.
AB  - In this paper, a nanosecond LIFT process is analyzed both from experimental and
      modeling points of view. Experimental results are first presented and compared to
      simple estimates obtained from physical analysis, i.e. energy balance, jump
      relations and analytical pocket dynamics. Then a self-consistent 2D axisymmetric
      modeling strategy is presented. It is shown that data accessible from
      experiments, i.e. jet diameter and velocity, can be reproduced. Moreover, some
      specific mechanisms involved in the rear-surface deformation and jet formation
      may be described by some scales of hydrodynamic process, i.e. shock waves
      propagation and expansion waves, as a consequence of the laser heating. It shows
      that the LIFT process is essentially driven by hydrodynamics and thermal
      transfer, and that a coupled approach including self-consistent laser energy
      deposition, heating by thermal conduction and specific models for matter is
      required.

PMID- 20811119
TI  - Laser printing of cells into 3D scaffolds.
AB  - One of the most promising approaches in tissue engineering is the application of
      3D scaffolds, which provide cell support and guidance in the initial tissue
      formation stage. The porosity of the scaffold and internal pore organization
      influence cell migration and play a major role in its biodegradation dynamics,
      nutrient diffusion and mechanical stability. In order to control cell migration
      and cellular interactions within the scaffold, novel technologies capable of
      producing 3D structures in accordance with predefined design are required. The
      two-photon polymerization (2PP) technique, used in this report for the
      fabrication of scaffolds, allows the realization of arbitrary 3D structures with
      submicron spatial resolution. Highly porous 3D scaffolds, produced by 2PP of
      acrylated poly(ethylene glycol), are seeded with cells by means of laser-induced
      forward transfer (LIFT). In this laser printing approach, a propulsive force,
      resulting from laser-induced shock wave, is used to propel individual cells or
      cell groups from a donor substrate towards the receiver substrate. We demonstrate
      that with this technique printing of multiple cell types into 3D scaffolds is
      possible. Combination of LIFT and 2PP provides a route for the realization of 3D
      multicellular tissue constructs and artificial ECM engineered on the microscale.

PMID- 20811120
TI  - A droplet-based building block approach for bladder smooth muscle cell (SMC)
      proliferation.
AB  - Tissue engineering based on building blocks is an emerging method to fabricate 3D
      tissue constructs. This method requires depositing and assembling building blocks
      (cell-laden microgels) at high throughput. The current technologies (e.g.,
      molding and photolithography) to fabricate microgels have throughput challenges
      and provide limited control over building block properties (e.g., cell density).
      The cell-encapsulating droplet generation technique has potential to address
      these challenges. In this study, we monitored individual building blocks for
      viability, proliferation and cell density. The results showed that (i) SMCs can
      be encapsulated in collagen droplets with high viability (>94.2 +/- 3.2%) for
      four cases of initial number of cells per building block (i.e. 7 +/- 2, 16 +/- 2,
      26 +/- 3 and 37 +/- 3 cells/building block). (ii) Encapsulated SMCs can
      proliferate in building blocks at rates that are consistent (1.49 +/- 0.29)
      across all four cases, compared to that of the controls. (iii) By assembling
      these building blocks, we created an SMC patch (5 mm x 5 mm x 20 microm), which
      was cultured for 51 days forming a 3D tissue-like construct. The histology of the
      cultured patch was compared to that of a native rat bladder. These results
      indicate the potential of creating 3D tissue models at high throughput in vitro
      using building blocks.

PMID- 20811121
TI  - Surface biofunctionalization and production of miniaturized sensor structures
      using aerosol printing technologies.
AB  - The work described in this paper demonstrates that very small protein and DNA
      structures can be applied to various substrates without denaturation using
      aerosol printing technology. This technology allows high-resolution deposition of
      various nanoscaled metal and biological suspensions. Before printing, metal and
      biological suspensions were formulated and then nebulized to form an aerosol
      which is aerodynamically focused on the printing module of the system in order to
      achieve precise structuring of the nanoscale material on a substrate. In this
      way, it is possible to focus the aerosol stream at a distance of about 5 mm from
      the printhead to the surface. This technology is useful for printing fluorescence
      marked proteins and printing enzymes without affecting their biological activity.
      Furthermore, higher molecular weight DNA can be printed without shearing. The
      advantages, such as printing on complex, non-planar 3D structured surfaces, and
      disadvantages of the aerosol printing technology are also discussed and are
      compared with other printing technologies. In addition, miniaturized sensor
      structures with line thicknesses in the range of a few micrometers are fabricated
      by applying a silver sensor structure to glass. After sintering using an
      integrated laser or in an oven process, electrical conductivity is achieved
      within the sensor structure. Finally, we printed BSA in small micrometre-sized
      areas within the sensor structure using the same deposition system. The aerosol
      printing technology combined with material development offers great advantages
      for future-oriented applications involving biological surface functionalization
      on small areas. This is important for innovative biomedical micro-device
      development and for production solutions which bridge the disciplines of biology
      and electronics.

PMID- 20811122
TI  - Machine design and processing considerations for the 3D plotting of thermoplastic
      scaffolds.
AB  - 3D plotting by micro-extrusion is a promising layer-wise fabrication method for
      the production of scaffolds in thermoplastic polymers. It is a solvent-free
      direct technique which permits extensive control over geometry and porosity. This
      paper highlights the complications that arise when using this technique for the
      processing of thermally sensitive polymers. It has been noted that the material
      is subject to extensive thermal load during processing, which may result in
      degradation by chain scission. This negatively affects scaffold (mechanical)
      properties as well as predictability and repeatability of the fabrication
      technique. A rationale is offered as to the main causes of this thermally induced
      degradation during processing and tentative ideas towards a solution are equally
      put forward.

PMID- 20811123
TI  - Bio rapid prototyping by extruding/aspirating/refilling thermoreversible
      hydrogel.
AB  - This paper reports a method for rapid prototyping of cell tissues, which is based
      on a system that extrudes, aspirates and refills a mixture of cells and
      thermoreversible hydrogel as a scaffold. In the extruding mode, a cell-mixed
      scaffold solution in the sol state is extruded from a cooled micronozzle into a
      temperature-controlled substrate, which keeps the scaffold in the gel state. In
      the aspiration mode, the opposite process is performed by Bernoulli suction. In
      the refilling mode, the solution is extruded into a groove created in the
      aspiration mode. The minimum width of extruded hydrogel pattern is 114 +/- 15
      microm by employing a nozzle of diameter 100 microm, and that of aspirated groove
      was 355 +/- 10 microm using a 500 microm-diameter nozzle. Gum arabic is mixed
      with the scaffold solution to avoid peeling-off of the gel pattern from the
      substrate. Patterning of Sf-9 cell tissue is demonstrated, and the stability of
      the patterned cell is investigated. This system offers a procedure for rapid
      prototyping and local modification of cell scaffolds for tissue engineering.

PMID- 20811124
TI  - Accelerated differentiation of osteoblast cells on polycaprolactone scaffolds
      driven by a combined effect of protein coating and plasma modification.
AB  - A combined effect of protein coating and plasma modification on the quality of
      the osteoblast-scaffold interaction was investigated. Three-dimensional
      polycaprolactone (PCL) scaffolds were manufactured by the precision extrusion
      deposition (PED) system. The structural, physical, chemical and biological cues
      were introduced to the surface through providing 3D structure, coating with
      adhesive protein fibronectin and modifying the surface with oxygen-based plasma.
      The changes in the surface properties of PCL after those modifications were
      examined by contact angle goniometry, surface energy calculation, surface
      chemistry analysis (XPS) and surface topography measurements (AFM). The effects
      of modification techniques on osteoblast short-term and long-term functions were
      examined by cell adhesion, proliferation assays and differentiation markers,
      namely alkaline phosphatase activity (ALP) and osteocalcin secretion. The results
      suggested that the physical and chemical cues introduced by plasma modification
      might be sufficient for improved cell adhesion, but for accelerated osteoblast
      differentiation the synergetic effects of structural, physical, chemical and
      biological cues should be introduced to the PCL surface.

PMID- 20811125
TI  - Biomatrices and biomaterials for future developments of bioprinting and
      biofabrication.
AB  - The next step beyond conventional scaffold-based tissue engineering is cell-based
      direct biofabrication techniques. In industrial processes, various three
      dimensional (3D) prototype models have been fabricated using several different
      rapid prototyping methods, such as stereo-lithography, 3D printing and laser
      sintering, as well as others, in which a variety of chemical materials are
      utilized. However, with direct cell-based biofabrication, only biocompatible
      materials can be used, and the manufacturing process must be performed under
      biocompatible and physiological conditions. We have developed a direct 3D cell
      printing system using inkjet and gelation techniques with inkjet droplets, and
      found that it had good potential to construct 3D structures with multiple types
      of cells. With this system, we have used alginate and fibrin hydrogel materials,
      each of which has advantages and disadvantages. Herein, we discuss the roles of
      hydrogel for biofabrication and show that further developments in biofabrication
      technology with biomatrices will play a major part, as will developments in
      manufacturing technology. It is important to explore suitable biomatrices as the
      next key step in biofabrication techniques.

PMID- 20811126
TI  - Development of human umbilical vein endothelial cell (HUVEC) and human umbilical
      vein smooth muscle cell (HUVSMC) branch/stem structures on hydrogel layers via
      biological laser printing (BioLP).
AB  - Angiogenesis is one of the prerequisite steps for viable tissue formation. The
      ability to influence the direction and structure in the formation of a vascular
      system is crucial in engineering tissue. Using biological laser printing (BioLP),
      we fabricated branch/stem structures of human umbilical vein endothelial cells
      (HUVEC) and human umbilical vein smooth muscle cells (HUVSMC). The structure is
      simple as to mimic vascular networks in natural tissue but also allow cells to
      develop new, finer structures away from the stem and branches. Additionally, we
      printed co-culture structures by first depositing only HUVECs, followed by 24 h
      incubation to allow for adequate cell-cell communication and differentiation into
      lumina; these cell printed scaffold layers were then removed from incubation and
      inserted into the BioLP apparatus so that HUVSMCs could be directly deposited on
      top and around the previously printed HUVEC structures. The growth and
      differentiation of these co-culture structures was then compared to the growth of
      printed samples with either HUVECs or HUVSMCs alone. Lumen formation was found to
      closely mimic the original branch and stem structure. The beginning of a network
      structure is observed. HUVSMCs acted to limit HUVEC over-growth and migration
      when compared to printed HUVEC structures alone. HUVSMCs and HUVECS, when printed
      in close contact, appear to form cell-cell junctions around lumen-like
      structures. They demonstrate a symbiotic relationship which affects their
      development of phenotype when in close proximity of each other. Our results
      indicate that it is possible to direct the formation and growth of lumen and
      lumen network using BioLP.

PMID- 20811128
TI  - Biofabrication to build the biology-device interface.
AB  - The last century witnessed spectacular advances in both microelectronics and
      biotechnology yet there was little synergy between the two. A challenge to their
      integration is that biological and electronic systems are constructed using
      divergent fabrication paradigms. Biology fabricates bottom-up with labile
      components, while microelectronic devices are fabricated top-down using methods
      that are 'bio-incompatible'. Biofabrication--the use of biological materials and
      mechanisms for construction--offers the opportunity to span these fabrication
      paradigms by providing convergent approaches for building the bio-device
      interface. Integral to biofabrication are stimuli-responsive materials (e.g. film
      forming polysaccharides) that allow directed assembly under near physiological
      conditions in response to device-imposed signals. Biomolecular engineering,
      through recombinant technology, allows biological components to be endowed with
      information for assembly (e.g. encoded in a protein's amino acid sequence).
      Finally, self-assembly and enzymatic assembly provide the mechanisms for
      construction over a hierarchy of length scales. Here, we review recent advances
      in the use of biofabrication to build the bio-device interface. We anticipate
      that the biofabrication toolbox will expand over the next decade as more
      researchers enlist the unique construction capabilities of biology. Further, we
      look forward to observing the application of this toolbox to create devices that
      can better diagnose disease, detect pathogens and discover drugs. Finally, we
      expect that biofabrication will enable the effective interfacing of biology with
      electronics to create implantable devices for personalized and regenerative
      medicine.

PMID- 20811129
TI  - Wetting effects on in vitro bioactivity and in vitro biocompatibility of laser
      micro-textured Ca-P coating.
AB  - Calcium phosphate (Ca-P) coating on the Ti-6Al-4V alloy enhances osteoblast
      adhesion and tissue formation at the bone implant interface. In light of this, in
      the current work a laser-based coating technique was used to synthesize two
      different micro-textured (100 microm and 200 microm spaced line patterns) Ca-P
      coatings on the Ti-6Al-4V alloy and its effect on wettability and osteoblast cell
      adhesion were systematically studied. X-ray diffraction (XRD) analysis of the
      coated samples indicated the presence of precursor material, Ca10(PO4)6(OH)2 (HA)
      and various other additional phases such as CaTiO3, Ca3(PO4)2, TiO2 (anatase) and
      TiO2 (rutile) owing to the reaction between the precursor (HA) and substrate (Ti
      6Al-4V) during laser processing. Confocal laser scanning microscopy-based
      characterization of coated samples indicated that the samples processed at 100
      microm line spacing demonstrated a reduced surface roughness and smaller texture
      parameter value as compared to the samples processed at 200 microm spacing. The
      surface energy and wettability of the 100 microm spaced samples measured using a
      static sessile drop technique demonstrated higher surface energy and increased
      hydrophilicity as compared to the control (untreated Ti-6Al-4V) and the samples
      processed at 200 microm spacing. The tendency of coated samples for
      mineralization through generation of an apatite-like phase during immersion in a
      simulated body fluid was indicative of their in vitro bioactive nature. In light
      of higher surface energy and increased hydrophilicity the in vitro
      biocompatibility of the samples with 100 microm line spacing was demonstrated
      through increased cell proliferation and cell adhesion of mouse MC3T3-E1
      osteoblast-like cells.

PMID- 20811130
TI  - Fabricating a pearl/PLGA composite scaffold by the low-temperature deposition
      manufacturing technique for bone tissue engineering.
AB  - Here we developed a composite scaffold of pearl/poly(lactic-co-glycolic acid)
      (pearl/PLGA) utilizing the low-temperature deposition manufacturing (LDM). LDM
      makes it possible to fabricate scaffolds with designed microstructure and
      macrostructure, while keeping the bioactivity of biomaterials by working at a low
      temperature. Process optimization was carried out to fabricate a mixture of pearl
      powder, PLGA and 1,4-dioxane with the designed hierarchical structures, and
      freeze-dried at a temperature of -40 degrees C. Scaffolds with square and
      designated bone shape were fabricated by following the 3D model. Marrow stem
      cells (MSCs) were seeded on the pearl/PLGA scaffold and then cultured in a
      rotating cell culture system. The adhesion, proliferation and differentiation of
      MSCs into osteoblasts were determined using scanning electronic microscopy, WST-1
      assay, alkaline phosphatase activity assay, immunofluorescence staining and real
      time reverse transcription polymerase chain reaction. The results showed that the
      composite scaffold had high porosity (81.98 +/- 3.75%), proper pore size
      (micropores: <10 microm; macropore: 495 +/- 54 microm) and mechanical property
      (compressive strength: 0.81 +/- 0.04 MPa; elastic modulus: 23.14 +/- 0.75 MPa).
      The pearl/PLGA scaffolds exhibited better biocompatibility and osteoconductivity
      compared with the tricalcium phosphate/PLGA scaffold. All these results indicate
      that the pearl/PLGA scaffolds fulfill the basic requirements of bone tissue
      engineering scaffold.

PMID- 20811127
TI  - Tissue engineering by self-assembly and bio-printing of living cells.
AB  - Biofabrication of living structures with desired topology and functionality
      requires the interdisciplinary effort of practitioners of the physical, life and
      engineering sciences. Such efforts are being undertaken in many laboratories
      around the world. Numerous approaches are pursued, such as those based on the use
      of natural or artificial scaffolds, decellularized cadaveric extracellular
      matrices and, most lately, bioprinting. To be successful in this endeavor, it is
      crucial to provide in vitro micro-environmental clues for the cells resembling
      those in the organism. Therefore, scaffolds, populated with differentiated cells
      or stem cells, of increasing complexity and sophistication are being fabricated.
      However, no matter how sophisticated scaffolds are, they can cause problems
      stemming from their degradation, eliciting immunogenic reactions and other a
      priori unforeseen complications. It is also being realized that ultimately the
      best approach might be to rely on the self-assembly and self-organizing
      properties of cells and tissues and the innate regenerative capability of the
      organism itself, not just simply prepare tissue and organ structures in vitro
      followed by their implantation. Here we briefly review the different strategies
      for the fabrication of three-dimensional biological structures, in particular
      bioprinting. We detail a fully biological, scaffoldless, print-based engineering
      approach that uses self-assembling multicellular units as bio-ink particles and
      employs early developmental morphogenetic principles, such as cell sorting and
      tissue fusion.

PMID- 20811131
TI  - Effects of surfactant and gentle agitation on inkjet dispensing of living cells.
AB  - Inkjet dispensing is a promising method for patterning cells and biomaterials for
      tissue engineering applications. In a novel approach, this work uses a
      biocompatible surfactant to improve the reliability of droplet formation in
      piezoelectric drop-on-demand inkjet printing of Hep G2 hepatocytes onto
      hydrogels. During a long printing process, cell aggregation and sedimentation
      within the inkjet reservoir can lead to inconsistent printing results. In order
      to improve repeatability, the effects of gentle agitation on cell sedimentation
      and aggregation within the inkjet reservoir were also investigated. Cell
      viability and proliferation when printed onto prepared collagen substrates were
      assessed using live/dead staining and the Alamar Blue metabolic assay. The
      addition of 0.05% Pluronic as a surfactant did not reduce cell viability, which
      remained above 95% 2 days after printing. The surfactant improved the reliability
      of droplet formation. Although gentle stirring of the inkjet reservoir was
      sufficient to maintain a cell suspension and reduce sedimentation, aggregation
      within the suspension continued to affect printing performance over a 180 min
      printing period.

PMID- 20811132
TI  - Multifunctional polymeric vesicles for targeted drug delivery and imaging.
AB  - Multifunctional polymeric vesicles were developed for targeted drug delivery and
      imaging. To fabricate this system, a biodegradable amphiphilic diblock copolymer,
      folate-poly(ethylene glycol)-poly(D,L-lactide) was designed and synthesized
      through sequential anionic polymerization in a well-controlled manner.
      Hydrophobic superparamagnetic iron oxide nanoparticles were loaded into the
      hydrophobic membrane for ultra-sensitive magnetic resonance imaging. Meanwhile,
      the anticancer drug, doxorubicin was encapsulated in the aqueous core of the
      vesicles. Cell culture experiments demonstrated the potential of polymeric
      vesicles as an effective targeting nanoplatform for the delivery of anticancer
      drugs due to the folate attached to the surface of the vesicles.

PMID- 20811133
TI  - Multidisciplinary team and team oncology medicine research and development in
      China.
AB  - In the context of transition from "Biomedical Model" to "Biology-Psychology
      Society Medical Model", the treatment model of malignant tumors has changed from
      single-subject treatment to multidisciplinary collaboration treatment led by a
      Multidisciplinary Team (MDT). On this basis, the concept of "Team Oncology
      Medicine" strengthens the focus of malignant tumor treatment. This is not only
      improving cure rate and extending life span, but also paying close attention to
      patients' actual demands to improve their quality of life. There are many good
      studies and practices of Multidisciplinary Team and Team Oncology Medicine in the
      world. China is currently in the exploratory phase of the malignant tumor
      Multidisciplinary Team treatment model. Many hospitals have investigated and
      practiced a Multidisciplinary Team treatment model. China is faced with many
      problems to scientifically construct a malignant tumor treatment model which
      conforms to national conditions. These conditions include a medical model, a
      medical care insurance system, public hospitals reform, hospital management
      approaches, personnel framework, concern with patients' psychosis and psychology,
      and whether to tell patients their actual condition and how they should express
      their will, and so on.

PMID- 20811134
TI  - Longitudinal observation of influence of "taspo" on smoking behavior among high
      school students.
AB  - A system with an adult discrimination IC card "taspo" was introduced in 2008 to
      prevent minors from purchasing cigarettes in Japan. This study aimed to elucidate
      the short-term change in smoking behavior among a cohort of high school students
      through the introduction of the taspo system. We conducted a questionnaire survey
      in students at one high school in the metropolitan area of Japan in 2008. In this
      area, the taspo system was introduced on July 1, and the survey was conducted
      before and after its introduction (June and September). Change in smoking
      behavior was examined by linking the two questionnaires using a unique
      identification number for each participant. The questionnaire included basic
      characteristics, smoking-related behavior, and means of obtaining tobacco. Of 133
      students, 123 (response rate 84.7%) completed the before and after questionnaire
      forms and could be linked. The smoking rate was 22.8% in June and 25.2% in
      September, with no statistically significant change. Vending machines were the
      major means of obtaining tobacco in June, while the use of cigarette shops and
      supermarkets increased after the introduction of taspo. The introduction of taspo
      hardly influenced underage smoking behavior during the observation period in our
      study subjects. The only significant change was in the means of obtaining
      tobacco. To prevent underage smoking, the importance of comprehensive restriction
      of the procurement route was suggested.

PMID- 20811135
TI  - Bioinformatic analyses and an expression study of a novel gene associated with
      metabolic syndrome.
AB  - The investigation of novel genes involved in the derangement of glucose and lipid
      metabolism is of particular importance in understanding the development of
      metabolic syndrome (MS). In the present study, bioinformatic analyses were
      carried out to explore the structures and roles of the proteins encoded by the
      four cDNA sequences identified in our previous studies as associated with MS.
      Homology analyses demonstrated that the proteins encoded by Sequence 1, Sequence
      2, Sequence 3, and Sequence 4 were homologous with fibrinogen gamma polypeptide,
      liver fibrinogen-like 1, chromosome 10 open reading frame 104, and an unnamed
      protein product, respectively. Because the structures were well-known for
      fibrinogen gamma polypeptide and liver fibrinogen-like 1, further analyses were
      performed only for Sequence 3 and Sequence 4. Analyses of functional domains
      showed that the predicted proteins encoded by Sequence 3 and Sequence 4 had
      multiple phosphorylation and myristoylation sites. These results indicated that
      the two predicted proteins might be intermediate proteins in some signaling
      pathways. In order to explore the possible association of Sequence 3 with MS,
      HepG2 cells, a human hepatoma cell line, were treated with different
      concentrations of glucose (mannitol as osmotic control) for 48 h. Glucose at
      concentrations of 22 and 33.3 mM significantly increased the mRNA expression of
      Sequence 3 compared to glucose at 5.6 mM while mannitol had no significant effect
      on the mRNA expression of Sequence 3. These results indicated that the mRNA
      expression of Sequence 3 was positively associated with glucose higher than
      physiological concentrations.

PMID- 20811136
TI  - Translation and cross-cultural adaptation of the Pregnancy Physical Activity
      Questionnaire (PPAQ) to Japanese.
AB  - The aim of this study was to conduct a translation and cross-cultural adaptation
      of the Japanese version of the Pregnancy Physical Activity Questionnaire (PPAQ)
      that consisted of 36 items. We translated and adapted the PPAQ to the Japanese
      culture. This procedure included a forward step (stages I and II, translations
      and synthesis), quality control (stage III, back translation, and stage IV,
      expert committee review), and pre-testing (stage V). In the pre-test, the
      preliminary Japanese version was tested on ten Japanese pregnant subjects. The
      content, semantic, technical, conceptual, and experiential equivalents of
      cultural adaptation were discussed by the research members at each step. In the
      results section, one new item was added to address "riding a bicycle in order to
      go to a certain place other than for recreation or exercise", because many
      Japanese women often use a bicycle. The average age of the pregnant subjects in
      the pre-test was 32.7 years of age. The response time ranged from 5 to 15 min.
      Two subjects responded that they rode a bicycle under the new item. The
      preliminary Japanese version of the questionnaire was revised to reflect the
      opinions of pregnant subjects for cross-cultural adaptation, including the
      semantic, experiential, and technical equivalents. The consensus of content and
      conceptual equivalents of the pre-final version of PPAQ by discussion among the
      research members was obtained throughout these processes. The original developer
      approved all revisions. In conclusion, the pre-finalized Japanese version of the
      PPAQ was indicated to have cross-cultural equivalency with the original English
      version.

PMID- 20811137
TI  - Reliability and validity of a Nepalese version of the Kiddo-KINDL in adolescents.
AB  - The objective of this study was to assess the reliability and validity of a
      Nepalese version of the Kiddo-KINDL to measure Health-Related Quality of Life
      (HRQOL) in adolescents. We collected data from 204 students between 13 to 16
      years old from four secondary schools in Lalitpur district, Nepal. The students
      answered a Nepalese version of the Kiddo-KINDL and the Center for Epidemiological
      Studies-Depression Scale (CES-D) with a self-administrated questionnaire. We
      conducted a test-retest study on the instrument at an interval of 10 days and
      then compared the Kiddo-KINDL scores between the low CES-D score group and the
      high CES-D score group students. The instrument showed good reliability and a
      small response variation. The internal consistency (Cronbach's alpha) of the
      total score was 0.93. Corrected item-total correlations showed that all items
      ranged from 0.47 to 0.79. The reproducibility was satisfactory with an Intraclass
      Correlation Coefficient (ICC) of 0.88-0.95. The Kiddo-KINDL scores in the low CES
      D score group were significantly lower than those in the high CES-D score group
      students. The optimal cut-off score of the Kiddo-KINDL was estimated at 54.7,
      with an Area Under the Curve (AUC) score of 0.83 and both sensitivity (73.5%) and
      specificity (71.8%) were acceptably high. We recommended a mean change in Kiddo
      KINDL total scores of 4.0 to be used to define a minimal important difference
      according to two-point CES-D score changes. Our results showed that a Nepalese
      version of the Kiddo-KINDL has internal consistency, reproducibility,
      responsiveness, interpretability, and discriminant validity.

PMID- 20811138
TI  - Pattern and determinants of breast feeding and contraceptive practices among
      mothers within six months postpartum.
AB  - The present study aims to determine the patterns of breast feeding, return of
      menstruation, and contraceptive practices in the first six months postpartum in
      women visiting the outpatient department at a teaching hospital in Lucknow,
      Northern India. Mothers of infants between six to eight months of age visiting
      the outpatient department of Era's Lucknow Medical College were interviewed
      regarding breast feeding practices, return of menstruation, sexual activity, and
      contraceptive practices within the first six months postpartum using a structured
      questionnaire. Of all women interviewed only 75.8% practiced exclusive breast
      feeding with the mean duration of exclusive breast feeding (EBF) being 3.5 months
      with only 41% practicing EBF for six months, 28% were sexually active within six
      weeks postpartum, 64.5% women had a return of menstruation within six months.
      Contraception was practiced by only 54.4% women with a barrier method such as a
      condom, being the most common. Better education was the only factor significantly
      affecting EBF (p < 0.004) and use of contraception (p < 0.027). There were a
      total of 10 pregnancies within six months postpartum. In conclusion, optimal
      breast feeding practices are poor in this part of the country and lactational
      amenorrhoea cannot be effectively and reliably used as a method of contraception.
      Therefore, optimal breast feeding practices, timely introduction of contraception
      and institutional delivery need to be encouraged.

PMID- 20811139
TI  - Anti-aggressive activity of a standardized extract of Marsilea minuta Linn. in
      rodent models of aggression.
AB  - The present study was undertaken to evaluate in vivo anti-aggressive potential of
      a standardized extract of Marsilea minuta Linn. (Marsileaceae). The standardized
      extract of Marsilea minuta was evaluated for its potential effects against
      defensive and offensive aggressive behavior models of rodents. Marsilea minuta
      extract was orally administered at three dose levels (100, 200, and 400 mg/kg BW)
      once daily for 14 consecutive days as a suspension in polyethylene glycol (PEG),
      diazepam (2.5 mg/kg, p.o.) was used as a standard anti-aggressive agent. Control
      group animals were given an equal volume of vehicle (10%, v/v, PEG suspension).
      Anti-aggressive activity was evaluated using the following validated models of
      aggression, viz.: foot shock-induced aggression, isolation-induced aggression and
      resident-intruder aggression, in rodents. As a result, Marsilea minuta extract
      showed dose dependant anti-aggressive activity in the aforementioned, validated
      models of aggression. This suggests that the extract from Marsilea minuta has a
      promising anti-aggressive activity qualitatively comparable to that of diazepam.

PMID- 20811140
TI  - Identification of mouse mutant cells exhibiting the plastic mutant phenotype.
AB  - The initial processes involved in radiation carcinogenesis have not been clearly
      elucidated. We isolated mouse mutant cells exhibiting plasticity in their
      mutation phenotypes. These mutant cells were originally isolated from an
      irradiated cell population as 6-thioguanine resistant (6TGR) mutants that were
      deficient in hypoxanthine phosphoribosyl transferase (Hprt, E.C.2.4.2.8) activity
      at the frequency of approximately 6.2 x 10(-5). Approximately 10% of 6TGR cells
      showed plasticity in their mutant phenotypes and reverted to HAT-resistant
      (HATR), which is Hprt-proficient, wild type phenotype. Eventually we identified
      the plastic mutants in the un-irradiated wild type cell population as well and
      found that ionizing irradiation enhanced the frequency of the plastic mutation
      approximately 24 times. Treatment with 5-aza-cytidine did not affect the
      plasticity of mutant phenotypes identified in this study, suggesting that DNA
      methylation was not involved in the plastic changes of the mutant phenotypes. The
      plastic mutant phenotype identified in our study is a new type of genomic
      instability induced by ionizing irradiation, and it is likely to be involved in
      one of the primary changes that occur in the process of radiation carcinogenesis,
      and may explain one element of carcinogenesis, which is composed of multi-stages.

PMID- 20811141
TI  - Case report: Huge amoebic liver abscesses in both lobes.
AB  - We describe the case of a patient who returned to China from Africa and underwent
      emergency open surgical drainage with evacuation of 600 mL of anchovy sauce-like
      fluid from hepatic lesions. Computed tomography scans and surgical findings
      indicated abscesses in both hemilivers and communication between them.
      Bacteriological investigation of the fluid yielded negative results, but DNA
      assay of the pus detected 18S rRNA genes of Entamoeba histolytica. Serum anti
      amoebic antibodies were detected using an indirect fluorescent-antibody test.
      Consequently, anti-amoebic drugs were administered and drainage was performed,
      leading to improvement in the patient's condition. As is evident from this case,
      an amoebic liver abscess in the left hepatic lobe is rare but treatable.

PMID- 20811142
TI  - What is new in neuro-musculoskeletal interactions: from medical myths to YouTube.

PMID- 20811143
TI  - Reporting whole-body vibration intervention studies: recommendations of the
      International Society of Musculoskeletal and Neuronal Interactions.
AB  - Whole-body vibration (WBV) is receiving increasing interest as a therapeutic
      modality to improve neuromuscular performance or to increase bone mass or
      density. In order to help improve the quality of reports about WBV treatment
      studies, the International Society of Musculoskeletal and Neuronal Interactions
      (ISMNI) invited experts in the field to provide suggestions on how the
      intervention should be described in such reports. The recommendations are
      presented here.

PMID- 20811144
TI  - Assessment of bone response to conditioning exercise in the radius and tibia of
      young thoroughbred horses using pQCT.
AB  - OBJECTIVES: To assess the effect of conditioning exercise on bone parameters at
      multiple sites in the radius and tibia of young Thoroughbred horses. METHODS: The
      left and right radius and tibia were obtained from twelve horses, six of which
      had received conditioning exercise and six which formed the control group. Each
      bone was scanned at 5% intervals along its entire length using pQCT. RESULTS:
      Bone strength, bone area and periosteal circumference were significantly greater
      for the group of conditioned horses in both the radius and tibia. Volumetric bone
      mineral density was lower while bone mineral content, endocortical circumference
      and polar moment of inertia were higher in the conditioned group of horses but
      the significance of these differences varied between the two bones. Cortical
      thickness was not significantly different between the groups in either bone.
      CONCLUSIONS: Conditioning exercise stimulated a significant increase in the
      strength of both bones that could be attributed mainly to an increase in bone
      size, rather than differences in bone mineral content or density. The radius and
      tibia exhibited differences in the significance of changes in several bone
      parameters suggesting that not all bones respond in an identical fashion to
      imposed exercise.

PMID- 20811145
TI  - The 2nd Berlin BedRest Study: protocol and implementation.
AB  - Long-term bed-rest is used to simulate the effect of spaceflight on the human
      body and test different kinds of countermeasures. The 2nd Berlin BedRest Study
      (BBR2-2) tested the efficacy of whole-body vibration in addition to high-load
      resisitance exercise in preventing bone loss during bed-rest. Here we present the
      protocol of the study and discuss its implementation. Twenty-four male subjects
      underwent 60-days of six-degree head down tilt bed-rest and were randomised to an
      inactive control group (CTR), a high-load resistive exercise group (RE) or a high
      load resistive exercise with whole-body vibration group (RVE). Subsequent to
      events in the course of the study (e.g. subject withdrawal), 9 subjects
      participated in the CTR-group, 7 in the RVE-group and 8 (7 beyond bed-rest day
      30) in the RE-group. Fluid intake, urine output and axiallary temperature
      increased during bed-rest (p < .0001), though similarly in all groups (p > or =
      .17). Body weight changes differed between groups (p < .0001) with decreases in
      the CTR-group, marginal decreases in the RE-group and the RVE-group displaying
      significant decreases in body-weight beyond bed-rest day-51 only. In light of
      events and experiences of the current study, recommendations on various aspects
      of bed-rest methodology are also discussed.

PMID- 20811146
TI  - A thermodynamic model of bone remodelling: the influence of dynamic loading
      together with biochemical control.
AB  - Understanding of the bone remodelling process has considerably increased during
      the last 20 years. Since the ability to simulate (and predict) the effects of
      bone remodelling offers substantial insights, several models have been proposed
      to describe this phenomenon. The strength of the presented model is that it
      includes biochemical control factors (e.g., the necessity of cell-to-cell
      contact, which is mediated by the RANKL-RANK-OPG chain during osteoclastogenesis)
      and mechanical stimulation, the governing equations are derived from interaction
      kinetics (e.g., mass is preserved in running reactions), and the parameters are
      measurable. Behaviour of the model is in accordance with experimental and
      clinical observations, such as the role of dynamic loading, the inhibitory effect
      of dynamic loading on osteoclastogenesis, the observation that polykaryon
      osteoclasts are activated and formed by a direct cell-to-cell contact, and the
      correct concentrations of osteoblasts, osteoclasts, and osteocytes. The model
      does not yet describe the bone remodelling process in complete detail, but the
      implemented simplifications describe the key features and further details of
      control mechanisms may be added.

PMID- 20811147
TI  - Mandibular bone density and calcium content affected by different kind of stress
      in mice.
AB  - OBJECTIVES: Stress is considered to affect many body and mental functions. This
      leads to activation of the hypothalamic-pituitary-adrenal axis and the
      adrenomedullary sympathetic system resulting to increased glucocorticoid release.
      Corticosteroids are known to cause systemic bone loss. The aim of the study was
      to investigate the role of different kinds of stress on the mandible bone mass of
      Wistar mice. METHODS: 75 male Wistar mice were divided into three groups (n=25
      each). The animals of group C were submitted to stress by electroshock with 22-45
      volts for a duration of 4 seconds each minute for one hour each day. Group B was
      submitted to isolation stress and group A was the control group. The duration of
      the experiment was 137 days. RESULTS: The adrenals weight was increased (group C
      vs group A, p<0.001; group B vs group A p<0.05), while urine hydroxyproline was
      reduced under stress. The calcium content of the mandible and the ratio between
      calcium content and mandible volume was decreased (p<0.05 for both groups).
      CONCLUSIONS: Mandibular bone mass was affected by different kinds of stress and
      may represent a considerable parameter for the diagnosis, prevention and
      treatment of bone mass deficiency.

PMID- 20811148
TI  - Age and sex differences of controlled force exertion measured by a computer
      generated quasi-random target-pursuit system.
AB  - OBJECTIVES: This study examined age and sex differences of controlled force
      exertion measured by a computer-generated quasi-random target-pursuit system in
      207 males and 249 females aged 15 to 86 years. METHODS: The participants matched
      submaximal grip exertion of their dominant hand to changing demand values,
      appearing as a moving quasi-random waveform on the display of a personal
      computer. They performed the test three times with 1-min intervals (one trial was
      40 sec). The total sum of the percent of differences between the demand value and
      the grip exertion value for 25 sec was used as an evaluation parameter. RESULTS:
      The errors in controlled force exertion tended to increase constantly with age in
      both sexes. Significant linear regressions were identified, but there was no
      significant difference in the rate of increase in both sexes. Analysis of
      variance showed nonsignificant sex differences among means, except for those in
      individuals older than 60 years; significant differences between means in the
      groups older than the 40 yr.-old age group and the 20-24 yr.-old group were found
      in both sexes. CONCLUSIONS: Controlled force exertion did not show a significant
      sex difference and decreased gradually with age in both sexes, but decreased
      remarkably after 40 years of age.

PMID- 20811149
TI  - Inhibition of TRPC6 degradation suppresses ischemic brain damage in rats.
AB  - Brain injury after focal cerebral ischemia, the most common cause of stroke,
      develops from a series of pathological processes, including excitotoxicity,
      inflammation, and apoptosis. While NMDA receptors have been implicated in
      excitotoxicity, attempts to prevent ischemic brain damage by blocking NMDA
      receptors have been disappointing. Disruption of neuroprotective pathways may be
      another avenue responsible for ischemic damage, and thus preservation of neuronal
      survival may be important for prevention of ischemic brain injury. Here, we
      report that suppression of proteolytic degradation of transient receptor
      potential canonical 6 (TRPC6) prevented ischemic neuronal cell death in a rat
      model of stroke. The TRPC6 protein level in neurons was greatly reduced in
      ischemia via NMDA receptor-dependent calpain proteolysis of the N-terminal domain
      of TRPC6 at Lys16. This downregulation was specific for TRPC6 and preceded
      neuronal death. In a rat model of ischemia, activating TRPC6 prevented neuronal
      death, while blocking TRPC6 increased sensitivity to ischemia. A fusion peptide
      derived from the calpain cleavage site in TRPC6 inhibited degradation of TRPC6,
      reduced infarct size, and improved behavioral performance measures via the cAMP
      response element-binding protein (CREB) signaling pathway. Thus, TRPC6
      proteolysis contributed to ischemic neuronal cell death, and suppression of its
      degradation preserved neuronal survival and prevented ischemic brain damage.

PMID- 20811151
TI  - Replacing adenoviral vector HVR1 with a malaria B cell epitope improves
      immunogenicity and circumvents preexisting immunity to adenovirus in mice.
AB  - Although adenovirus (Ad) has been regarded as an excellent vaccine vector, there
      are 2 major drawbacks to using this platform: (a) Ad-based vaccines induce a
      relatively weak humoral response against encoded transgenes, and (b) preexisting
      immunity to Ad is highly prevalent among the general population. To overcome
      these obstacles, we constructed an Ad-based malaria vaccine by inserting a B cell
      epitope derived from a Plasmodium yoelii circumsporozoite (CS) protein (referred
      to as the PyCS-B epitope) into the capsid proteins of WT/CS-GFP, a recombinant Ad
      expressing P. yoelii CS protein and GFP as its transgene. Multiple vaccinations
      with the capsid-modified Ad induced a substantially increased level of protection
      against subsequent malaria challenge in mice when compared with that of
      unmodified WT/CS-GFP. Increased protection correlated with augmented antibody
      responses against the PyCS-B epitope expressed in the capsid. Furthermore,
      replacement of hypervariable region 1 (HVR1) of the Ad capsid proteins with the
      PyCS-B epitope circumvented neutralization of the modified Ad by preexisting Ad
      specific antibody, both in vivo and in vitro. Importantly, the immunogenicity of
      the Ad-containing PyCS-B epitope in the HVR1 and a P. yoelii CS transgene was
      maintained. Overall, this study demonstrates that the HVR1-modifed Ad vastly
      improves upon Ad as a promising malaria vaccine platform candidate.

PMID- 20811150
TI  - Cardiac fibrosis in mice with hypertrophic cardiomyopathy is mediated by non
      myocyte proliferation and requires Tgf-beta.
AB  - Mutations in sarcomere protein genes can cause hypertrophic cardiomyopathy (HCM),
      a disorder characterized by myocyte enlargement, fibrosis, and impaired
      ventricular relaxation. Here, we demonstrate that sarcomere protein gene
      mutations activate proliferative and profibrotic signals in non-myocyte cells to
      produce pathologic remodeling in HCM. Gene expression analyses of non-myocyte
      cells isolated from HCM mouse hearts showed increased levels of RNAs encoding
      cell-cycle proteins, Tgf-beta, periostin, and other profibrotic proteins.
      Markedly increased BrdU labeling, Ki67 antigen expression, and periostin
      immunohistochemistry in the fibrotic regions of HCM hearts confirmed the
      transcriptional profiling data. Genetic ablation of periostin in HCM mice reduced
      but did not extinguish non-myocyte proliferation and fibrosis. In contrast,
      administration of Tgf-beta-neutralizing antibodies abrogated non-myocyte
      proliferation and fibrosis. Chronic administration of the angiotensin II type 1
      receptor antagonist losartan to mutation-positive, hypertrophy-negative
      (prehypertrophic) mice prevented the emergence of hypertrophy, non-myocyte
      proliferation, and fibrosis. Losartan treatment did not reverse pathologic
      remodeling of established HCM but did reduce non-myocyte proliferation. These
      data define non-myocyte activation of Tgf-beta signaling as a pivotal mechanism
      for increased fibrosis in HCM and a potentially important factor contributing to
      diastolic dysfunction and heart failure. Preemptive pharmacologic inhibition of
      Tgf-beta signals warrants study in human patients with sarcomere gene mutations.

PMID- 20811152
TI  - Pcif1 modulates Pdx1 protein stability and pancreatic beta cell function and
      survival in mice.
AB  - The homeodomain transcription factor pancreatic duodenal homeobox 1 (Pdx1) is a
      major mediator of insulin transcription and a key regulator of the beta cell
      phenotype. Heterozygous mutations in PDX1 are associated with the development of
      diabetes in humans. Understanding how Pdx1 expression levels are controlled is
      therefore of intense interest in the study and treatment of diabetes. Pdx1 C
      terminus-interacting factor-1 (Pcif1, also known as SPOP) is a nuclear protein
      that inhibits Pdx1 transactivation. Here, we show that Pcif1 targets Pdx1 for
      ubiquitination and proteasomal degradation. Silencing of Pcif1 increased Pdx1
      protein levels in cultured mouse beta cells, and Pcif1 heterozygosity normalized
      Pdx1 protein levels in Pdx1(+/-) mouse islets, thereby increasing expression of
      key Pdx1 transcriptional targets. Remarkably, Pcif1 heterozygosity improved
      glucose homeostasis and beta cell function and normalized beta cell mass in
      Pdx1(+/-) mice by modulating beta cell survival. These findings indicate that in
      adult mouse beta cells, Pcif1 limits Pdx1 protein accumulation and thus the
      expression of insulin and other gene targets important in the maintenance of beta
      cell mass and function. They also provide evidence that targeting the turnover of
      a pancreatic transcription factor in vivo can improve glucose homeostasis.

PMID- 20811154
TI  - TLR8 deficiency leads to autoimmunity in mice.
AB  - TLRs play an essential role in the induction of immune responses by detecting
      conserved molecular products of microorganisms. However, the function of TLR8 is
      largely unknown. In the current study, we investigated the role of TLR8 signaling
      in immunity in mice. We found that Tlr8(-/-) DCs overexpressed TLR7, were
      hyperresponsive to various TLR7 ligands, and showed stronger and faster NF-kappaB
      activation upon stimulation with the TLR7 ligand R848. Tlr8(-/-) mice showed
      splenomegaly, defective development of marginal zone (MZ) and B1 B cells, and
      increased serum levels of IgM and IgG2a. Furthermore, Tlr8(-/-) mice exhibited
      increased serum levels of autoantibodies against small nuclear
      ribonucleoproteins, ribonucleoprotein, and dsDNA and developed
      glomerulonephritis, whereas neither Tlr7(-/-) nor Tlr8(-/-)Tlr7(-/-) mice showed
      any of the phenotypes observed in Tlr8(-/-) mice. These data provide evidence for
      a pivotal role for mouse TLR8 in the regulation of mouse TLR7 expression and
      prevention of spontaneous autoimmunity.

PMID- 20811155
TI  - Cytoplasmic p21 expression levels determine cisplatin resistance in human
      testicular cancer.
AB  - Platinum-based chemotherapies such as cisplatin are used as first-line treatment
      for many cancers. Although there is often a high initial responsiveness, the
      majority of patients eventually relapse with platinum-resistant disease. For
      example, a subset of testicular cancer patients still die even though testicular
      cancer is considered a paradigm of cisplatin-sensitive solid tumors, but the
      mechanisms of chemoresistance remain elusive. Here, we have shown that one key
      determinant of cisplatin-resistance in testicular embryonal carcinoma (EC) is
      high cytoplasmic expression of the cyclin-dependent kinase (CDK) inhibitor p21.
      The EC component of the majority of refractory testicular cancer patients
      exhibited high cytoplasmic p21 expression, which protected EC cell lines against
      cisplatin-induced apoptosis via CDK2 inhibition. Localization of p21 in the
      cytoplasm was critical for cisplatin resistance, since relocalization of p21 to
      the nucleus by Akt inhibition sensitized EC cell lines to cisplatin. We also
      demonstrated in EC cell lines and human tumor tissue that high cytoplasmic p21
      expression and cisplatin resistance of EC were inversely associated with the
      expression of Oct4 and miR-106b seed family members. Thus, targeting cytoplasmic
      p21, including by modulation of the Oct4/miR-106b/p21 pathway, may offer new
      strategies for the treatment of chemoresistant testicular and other types of
      cancer.

PMID- 20811156
TI  - An eye for discovery.
AB  - Vision research has often led to significant advances in our understanding of
      biology. There has also been particular success in translating basic research in
      the eye into breakthrough clinical therapies that mark important milestones for
      ophthalmology and also for medical research. Anti-VEGF therapy for age-related
      macular degeneration was named as one of the top ten science advancements of the
      year 2006. Only two years later, successful transfer of the RPE65 gene into
      retinal pigment epithelium of patients with Leber congenital amaurosis was noted
      as one of the most important clinical applications of gene therapy. The articles
      in this Review series outline current developments in vision research and
      highlight its continued importance in ophthalmology and medicine.

PMID- 20811157
TI  - Stemming vision loss with stem cells.
AB  - Dramatic advances in the field of stem cell research have raised the possibility
      of using these cells to treat a variety of diseases. The eye is an excellent
      target organ for such cell-based therapeutics due to its ready accessibility, the
      prevalence of vasculo- and neurodegenerative diseases affecting vision, and the
      availability of animal models to demonstrate proof of concept. In fact, stem cell
      therapies have already been applied to the treatment of disease affecting the
      ocular surface, leading to preservation of vision. Diseases in the back of the
      eye, such as macular degeneration, diabetic retinopathy, and inherited retinal
      degenerations, present greater challenges, but rapidly emerging stem cell
      technologies hold the promise of autologous grafts to stabilize vision loss
      through cellular replacement or paracrine rescue effects.

PMID- 20811158
TI  - Retinopathy of prematurity: understanding ischemic retinal vasculopathies at an
      extreme of life.
AB  - Retinopathy of prematurity (ROP) is a major complication of preterm birth. It
      encompasses a spectrum of pathologies that affect vision, from mild disease that
      resolves spontaneously to severe disease that causes retinal detachment and
      subsequent blindness. The pathologies are characterized by an arrest in normal
      retinal vascular development associated with microvascular degeneration. The
      resulting ischemia and retinal hypoxia lead to excessive abnormal compensatory
      blood vessel growth. However, this neovascularization can lead to fibrous scar
      formation and culminate in retinal detachment. Present therapeutic modalities to
      limit the adverse consequences of aberrant neovascularization are invasive and/or
      tissue-destructive. In this Review, we discuss current concepts on retinal
      microvascular degeneration, neovascularization, and available treatments, as well
      as present future perspectives toward more profound elucidation of the
      pathogenesis of ROP.

PMID- 20811159
TI  - Therapeutic targets in age-related macular disease.
AB  - Age-related macular disease (AMD) accounts for more than 50% of blind
      registration in Western society. Patients with AMD are classified as having early
      disease, in which visual function is well preserved, or late disease, in which
      central vision is lost. Until recently, there was no therapy available by which
      the course of the disorder could be modified. Now, the most common form of late
      stage AMD - choroidal neovascularization - responds to treatment with anti-VEGF
      therapies; although visual loss is modified in a portion of these cases, no
      therapeutic approach exists that alters the evolution from early to late disease.
      However, as discussed in this Review, research over the last few years has
      demonstrated several features of AMD that are likely to be amenable to treatment.
      Potential targets for treatment are described, and possible therapeutic
      approaches are discussed.

PMID- 20811160
TI  - Lighting a candle in the dark: advances in genetics and gene therapy of recessive
      retinal dystrophies.
AB  - Nonsyndromic recessive retinal dystrophies cause severe visual impairment due to
      the death of photoreceptor and retinal pigment epithelium cells. These diseases
      until recently have been considered to be incurable. Molecular genetic studies in
      the last two decades have revealed the underlying molecular causes in
      approximately two-thirds of patients. The mammalian eye has been at the forefront
      of therapeutic trials based on gene augmentation in humans with an early-onset
      nonsyndromic recessive retinal dystrophy due to mutations in the retinal pigment
      epithelium-specific protein 65kDa (RPE65) gene. Tremendous challenges still lie
      ahead to extrapolate these studies to other retinal disease-causing genes, as
      human gene augmentation studies require testing in animal models for each
      individual gene and sufficiently large patient cohorts for clinical trials remain
      to be identified through cost-effective mutation screening protocols.

PMID- 20811161
TI  - How cortical neurons help us see: visual recognition in the human brain.
AB  - Through a series of complex transformations, the pixel-like input to the retina
      is converted into rich visual perceptions that constitute an integral part of
      visual recognition. Multiple visual problems arise due to damage or developmental
      abnormalities in the cortex of the brain. Here, we provide an overview of how
      visual information is processed along the ventral visual cortex in the human
      brain. We discuss how neurophysiological recordings in macaque monkeys and in
      humans can help us understand the computations performed by visual cortex.

PMID- 20811164
TI  - Diffusion-weighted magnetic resonance imaging for the healthy cervical
      multifidus: a potential method for studying neck muscle physiology following
      spinal trauma.
AB  - STUDY DESIGN: Cross-sectional. OBJECTIVE: To develop a new magnetic resonance
      imaging (MRI) measure for the diffusive properties of the healthy cervical
      multifidus and to determine the interrater and intrarater reliability of the
      measurement. BACKGROUND: Diffusion-weighted MRI, via calculation of the apparent
      diffusion coefficient (ADC), provides a representation of microscopic movements
      of water molecules in human tissues and may be useful to assess structural
      changes in neck muscle, as has been observed following whiplash. The optimal
      imaging parameters, however, have not been established. METHODS: A diffusion
      weighted MRI measure was developed, and, for the basic examination, the right
      cervical multifidus muscle at the C5 level was studied. A total of 6 asymptomatic
      volunteer individuals (3 females and 3 males) underwent a single diffusion
      weighted MRI scan. Interrater and intrarater agreement was evaluated using Bland
      Altman plots and intraclass correlation coefficients. RESULTS: Mean ADCb0-b50 and
      ADCb50-250 were significantly different from one another (P=.03). The plots
      confirmed the agreement of raters for ADC of the right cervical multifidus at C5.
      CONCLUSIONS: A quantitative and reliable diffusion-weighted MRI measure of
      cervical multifidus ADC has been described. There appears to be a fast and slow
      component ADC for the healthy multifidus, suggesting changes in extracellular and
      intracellular volume. Further comparative study is needed to quantify ADCs in the
      neck muscles in patients with traumatic whiplash.

PMID- 20811165
TI  - Lower extremity kinematics of females with patellofemoral pain syndrome while
      stair stepping.
AB  - STUDY DESIGN: Cross-sectional case-control design. BACKGROUND: Although the
      etiology of patellofemoral pain syndrome (PFPS) is not completely understood,
      there is some evidence to suggest that hip position during weight-bearing
      activities contributes to the disorder. OBJECTIVE: To compare the knee and hip
      motions (and their coordination) during stair stepping in female athletes with
      and without PFPS. METHODS: Two groups of female recreational athletes, 1 group
      with PFPS (n = 10) and a control group without PFPS (n = 10), were tested. All
      participants ascended and descended stairs (condition) at 2 speeds (self-selected
      comfortable and taxing [defined as 20% faster than the comfortable speed]), while
      the knee and hip angles were measured with a magnetic-based kinematic data
      acquisition system. Angle-angle diagrams were used to examine the relationship
      between flexion/extension of the knee and flexion/extension, adduction/abduction,
      and internal/external rotation of the hip. The angle of the knee and the 3 angles
      of the hip at foot contact on the third step were compared between groups by
      means of 3-way analyses of variance (ANOVA), with repeated measures on speed and
      condition. RESULTS: Group-by-speed interaction for knee angle was significant,
      with knee flexion being greater for the PFPS group for stair ascent and descent
      at a comfortable speed. Both the angle-angle diagrams and ANOVA demonstrated
      greater adduction and internal rotation of the hip in the individuals with PFPS
      compared to control participants during stair descent. CONCLUSION: Compared to
      control participants, females with PFPS descend stairs with the knee in a more
      flexed position and have the hip in a more adducted and internally rotated
      position at foot contact during stair stepping at a comfortable speed.

PMID- 20811162
TI  - Glaucoma: genes, phenotypes, and new directions for therapy.
AB  - Glaucoma, a leading cause of blindness worldwide, is characterized by progressive
      optic nerve damage, usually associated with intraocular pressure. Although the
      clinical progression of the disease is well defined, the molecular events
      responsible for glaucoma are currently poorly understood and current therapeutic
      strategies are not curative. This review summarizes the human genetics and
      genomic approaches that have shed light on the complex inheritance of glaucoma
      genes and the potential for gene-based and cellular therapies that this research
      makes possible.

PMID- 20811166
TI  - Functioning and disability in patients with hip osteoarthritis with mild to
      moderate pain.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To compare functioning and
      disability in patients with hip osteoarthritis (OA) not candidates for surgery,
      to a matched control group, and thereby to examine the relationship between the
      functioning and disability components used in this study in patients with hip OA.
      BACKGROUND: It is well known that patients with severe hip OA have deficits in
      functioning and disability. However, in patients with hip OA not candidates for
      surgery, the knowledge regarding functioning and disability is sparse. METHODS:
      Twenty-six patients (12 men, 14 women; mean age, 60 years) with radiographic and
      symptomatic hip OA were matched to 26 controls without hip pain. The following
      variables were measured: muscle strength using isokinetic peak force, hip passive
      range of motion, submaximal aerobic capacity using a cycling test, walking
      ability using the 6-minute walk test, self-reported pain, stiffness, and physical
      function using the Western Ontario and McMaster University Osteoarthritis Index,
      and health-related quality of life using the SF-36. RESULTS: The patients with
      hip OA had mild to moderate pain, as indicated by the Western Ontario and
      McMaster University Osteoarthritis Index, and significantly lower knee extension
      strength (mean difference [95% confidence interval {CI}]: -19.5 [-34.3, -4.7]
      Nm). Hip range of motion was significantly less in the patients with hip OA, with
      mean (95% CI) differences of -10 degrees  (-14 degrees , -6 degrees ) for
      extension, -18 degrees  (-26 degrees , -11 degrees ) for flexion, -9 degrees  (
      14 degrees , -4 degrees ) for abduction, -2 degrees  (-5 degrees , 0 degrees )
      for adduction, -16 degrees  (-23 degrees , -9 degrees ) for internal rotation,
      and -21 degrees  (-28 degrees , -14 degrees ) for external rotation. The patients
      with hip OA walked a significantly shorter distance in 6 minutes (mean
      difference, -75 m; 95% CI: -131, -20 m). There were no significant differences in
      hip extension/flexion, knee flexion, ankle dorsiflexion/plantar flexion muscle
      strength, or aerobic capacity between the 2 groups. There were significant
      associations between body function and activity components. CONCLUSION: Physical
      therapists should consider including quadriceps-strengthening and hip range-of
      motion exercises when developing rehabilitation programs for patients with hip
      OA, with mild to moderate pain, aiming to improve functioning and reduce
      disability.

PMID- 20811163
TI  - A look at autoimmunity and inflammation in the eye.
AB  - Autoimmune and inflammatory uveitis are a group of potentially blinding
      intraocular inflammatory diseases that arise without a known infectious trigger
      and are often associated with immunological responses to unique retinal proteins.
      In the United States, about 10% of the cases of severe visual handicap are
      attributed to this group of disorders. As I discuss here, experimental models of
      ocular autoimmunity targeting retinal proteins have brought about a better
      understanding of the basic immunological mechanisms involved in the pathogenesis
      of uveitis and are serving as templates for the development of novel therapies.

PMID- 20811167
TI  - Evaluation of the anterior pituitary function in the acute phase after
      spontaneous subarachnoid hemorrhage.
AB  - BACKGROUND: Subarachnoid hemorrhage (SAH) is a potential cause of
      hypopituitarism. Most of the studies regarding the relationship between SAH and
      anterior pituitary function were retrospective and hormonal assessment was
      performed several months after SAH. AIM: To prospectively evaluate the prevalence
      of anterior pituitary hormone deficiencies in the acute phase after spontaneous
      SAH and their possible correlation with clinical and radiological parameters.
      METHODS: Pituitary function was tested in 60 patients within 72 h after
      spontaneous SAH. RESULTS: 56.9% of the patients showed at least one anterior
      pituitary hormone deficiency: gonadotropin and GH secretion failure represented
      the most prevalent hormonal deficiencies (33.3 and 22.0%, respectively), whereas
      ACTH and TSH deficiency was less frequent (7.1 and 1.8%, respectively). With the
      exception of secondary hypogonadism, the prevalence of other pituitary hormone
      deficiencies is in agreement with previous studies, which evaluated pituitary
      function on longterm follow up after SAH. No correlation was found between
      hypopituitarism and clinical status, as assessed with Hunt-Hess and Glascow Coma
      Scales. Moreover, no correlation was found between hypopituitarism and bleeding
      severity evaluated with Fisher's scale. CONCLUSIONS: We demonstrated a high
      prevalence of anterior pituitary hormone deficiencies acutely after SAH. Although
      part of GH and gonadotropin deficiencies might be a consequence of functional
      alteration due to SAH itself, the finding of low cortisol levels in this
      stressful condition strongly suggests the presence of true hypocortisolism.
      Therefore, an evaluation of pituitary function shortly after SAH might be useful
      to identify a subset of patients who deserve a more accurate follow-up.

PMID- 20811168
TI  - A controlled trial of envelope colour for increasing response rates in older
      women.
AB  - BACKGROUND AND AIMS: Postal questionnaires are widely used in health research to
      provide measurable outcomes in areas such as quality of life. Participants who
      fail to return postal questionnaires can introduce non-response bias. Previous
      studies within populations over the age of 65 years have shown that response
      rates amongst older people can be 60% or less. The current study sought to
      investigate whether envelope colour affected response rates in a study about the
      effectiveness of screening older women for osteoporosis. METHODS: A total of 2803
      eligible female participants aged between 70 and 85 were sent an invitation pack
      from their GP practice. The invitation was either in a brown or white envelope
      and contained a matching pre-paid reply envelope. A study questionnaire was also
      sent out in brown or white envelopes 1 week after consenting to participate in
      the trial. RESULTS: The overall response rate was 78%. There was little evidence
      of an effect of envelope colour on response to the invitation to participate in
      the trial (OR 1.04, 95% CI 0.87-1.24). Similarly, there was no influence of
      envelope colour on the number of participants returning their questionnaires (OR
      0.99, 95% CI 0.60-1.63). There was weak evidence of an effect of envelope colour
      on the response rates of the consent process (OR 0.86, 95% CI 0.74-1.00). When we
      updated a recent meta-analysis with the results of this study, there was a non
      statistically- significant trend for greater response rates with brown envelopes
      compared with white envelopes (OR 1.19, 95% CI 0.86-1.64, I2=92%). However, the
      results where influenced by one study and when this study was excluded the pooled
      estimate was 0.98 (95% CI 0.89-1.08, I2=0%). CONCLUSION: This study found no
      evidence to suggest envelope colour has an effect on response to participate in a
      trial or questionnaire returns. There is weak evidence to suggest envelope colour
      may affect consent into a trial.

PMID- 20811169
TI  - A conservative management is preferable in milder forms of pituitary tumor
      apoplexy.
AB  - AIM: Our objective was to report a single-center experience of the management of
      pituitary tumor apoplexy. PATIENTS AND METHODS: We retrospectively analyzed a
      series of 44 patients hospitalized for pituitary apoplexy between January 1996
      and March 2008 at the Timone Hospital, Marseille, France. RESULTS: Most frequent
      presenting symptoms were headaches (93%), visual impairment (85%) and vomiting
      (59%). Hypopituitarism was present at diagnosis in 88% of patients, with a high
      incidence of corticotroph deficiency (70%). A risk factor was found in 52% of
      patients, mostly hypertension. Apoplexy occurred in a previously undiagnosed
      pituitary adenoma in 32/44 cases (73%). The apoplectic event concerned 12
      secreting, 27 non-functioning, 4 uncharacterized adenomas and one Rathke's pouch
      cyst. Nineteen patients underwent surgery within the first month, and one patient
      had conventional radiotherapy. Twenty-four patients, who had no ophthalmic or
      neurological signs, were conservatively treated in first intention; among them, 6
      received high dose corticosteroids. After a median follow-up of 21 months, there
      was no significant difference in terms of endocrine or visual recovery between
      the operated and the conservatively treated groups, nor between patients treated
      with corticosteroids or not. Panhypopituitarism was observed in 52% of patients,
      but partial or complete visual recovery was present in the majority of patients
      (91%), whatever the therapeutic approach. CONCLUSION: The outcome of patients
      treated with or without surgery for pituitary apoplexy without severe neuro
      ophthalmic deficits seems to be identical, pleading for a conservative management
      of pituitary apoplexy in the absence of visual emergency.

PMID- 20811171
TI  - Successful percutaneous management of acute left ventricular assist device
      stoppage.
AB  - The HeartMate II left ventricular assist device (LVAD) is a small axial-flow next
      generation pump. Acute stoppage of this device is a potentially lethal
      complication. As these devices proliferate, many patients will be in areas remote
      to their implant center. Therefore, percutaneous stabilization of these patients
      before definitive surgical replacement could be potentially life saving. We
      present two cases of acute LVAD stoppage managed successfully using percutaneous
      means.

PMID- 20811172
TI  - Nosocomial transmission of Cupriavidus pauculus during extracorporeal membrane
      oxygenation.
AB  - Patients undergoing extracorporeal membrane oxygenation (ECMO) are at increased
      risk of infection. We present the first known report of nosocomial infection with
      Cupriavidus pauculus attributable to contamination from ECMO equipment and
      describe the measures taken to halt subsequent infections. A cluster of
      infections in ECMO patients should prompt team members to consider contamination
      of equipment with environmental pathogens as a possible cause.

PMID- 20811173
TI  - A case of a maintenance hemodialysis patient in whom a change of sensitivity to
      acetate was suspected.
AB  - Sodium acetate, which is a buffering agent in dialysates, has a vasodilatation
      effect as well as effects for depression of myocardial contractility even in low
      dosages. Also, it is presumed to be one of the causes of hypotension during
      hemodialysis (HD). In recent years, acetate-free dialysates [A(-)D] have been
      developed. In this case, although it was possible to maintain a relatively stable
      hemodynamic condition during HD using 10 mEq/L of acetate-containing dialysate
      [A(+)D], after HD using A(-)D for 4 months and then switched back to A(+)D, the
      patient complained of several symptoms such as nausea, vomiting, and headache,
      and severe hypotension episodes increased during HD. Furthermore, stabilization
      of the hemodynamic condition was obtained after switching back to A(-)D.
      Moreover, the nutritional state and anemia were improved. Conventionally, it has
      been considered that cases referred to as acetate intolerance have various
      symptoms with increasing blood acetate levels; however, this case suggests the
      possibility that tolerance to acetate was acquired by using the A(+)D over time,
      and the tolerance dissipated after using the A(-)D for 4 months. The number of
      cases involving broadly defined acetate intolerance as in this case was higher
      than expected. These findings suggest that using A(-)D for such cases, it may
      therefore be possible to maintain stable hemodynamic conditions during HD and
      improve the nutritional state and anemia.

PMID- 20811175
TI  - The scientific evidence for acute pain treatment.
AB  - PURPOSE OF REVIEW: The quantity and quality of evidence available for the
      management of acute pain has grown rapidly over the last 20 years. Rather than
      listing current evidence related to specific acute pain treatments, the purpose
      of this review is to look at recent evidence in terms of its availability and
      ease of access, synthesis and incorporation into clinical practice as well as
      some of its limitations. RECENT FINDINGS: An increasing number of evidence-based
      medicine tools are available to assist clinicians in the provision of acute pain
      treatments. However, integration of this population-based evidence with clinical
      expertise, different patient factors and resource availability in different
      practice settings is still required if the best outcome is to be achieved for
      each patient. SUMMARY: It is difficult for clinicians to remain updated and
      synthesize all the evidence available relating to the treatment of acute pain.
      Assistance is available, but there may be limitations to some of the evidence
      presented and its application to different aspects of clinical practice and
      different patient groups.

PMID- 20811176
TI  - Introduction: value of regional anesthesia.

PMID- 20811177
TI  - Current world literature. Neuroanaesthesia. Pain medicine. Regional anaesthesia.

PMID- 20811178
TI  - "Take aways" for moving toward prevention: home care can play an important role!

PMID- 20811179
TI  - FDA approves new treatment for late-onset Pompe disease.

PMID- 20811180
TI  - 7 tools to assist hospice and home care clinicians in pain management at end of
      life.
AB  - Assessing pain at end of life is often a challenge for the home health clinician,
      especially in different age groups or in the presence of severe cognitive
      impairment, language barriers, or communication difficulties. The task of
      assessing and monitoring the severity of pain and measuring the effectiveness of
      treatment measures is essential for effective pain management. This article
      provides home health clinicians with some practical skills and essential tools to
      assess and record pain intensity as the first step for effective pain management.

PMID- 20811182
TI  - Infection control in soup kitchens and shelters.
AB  - This article explains one community's efforts to decrease infectious diseases in
      their community through a proactive approach among the homeless population. Due
      to the frequency with which the homeless population interfaces with other
      community members, it is time that infectious disease management among the
      homeless be incorporated into settings where the homeless population accesses
      services. Home health nurses can be the link to the community's efforts to
      develop and deliver infection control programs for the homeless population.

PMID- 20811183
TI  - Building a peer mentor home health aide program: implications for home health
      aide retention.
AB  - The Home Health Aide (HHA) industry is challenged with low wages, little
      possibility of career advancement, and high turnover rates. Jewish Home Lifecare,
      Home Assistance Personnel Inc. (HAPI) is a home care aide agency that has
      developed a Peer Mentor HHA program. Peer Mentor HHAs mentor newly hired/trained
      HHAs within our agency. This career path leads to higher paying work that allows
      for growth of our workforce for the identified growing care need and positively
      impacts HHA retention.

PMID- 20811184
TI  - Evaluating home health intravenous infusion referrals.

PMID- 20811186
TI  - Do delays in initiation of home healthcare services following hospital discharge
      affect patient outcomes?

PMID- 20811187
TI  - Innovation and experimentation in chronic care management will drive enduring
      healthcare reform.

PMID- 20811189
TI  - Cranial expansion in an infant with malignant osteopetrosis.

PMID- 20811190
TI  - Syndrome of inappropriate secretion of antidiuretic hormone and rhabdomyolysis
      complicating rhytidectomy.

PMID- 20811188
TI  - Treatment of common congenital hand conditions.
AB  - LEARNING OBJECTIVES: After reading this article, the participant should be able
      to: 1. Recognize the clinical features associated with five common congenital
      hand conditions. 2. Describe the indications and appropriate timing for various
      surgical procedures used to treat congenital hand anomalies. 3. Identify the
      pearls and pitfalls of these surgical treatments to avoid complications. 4.
      Understand the expected postoperative outcomes associated with these surgical
      procedures. SUMMARY: This article provides an introduction to congenital hand
      differences by focusing on practical surgical strategies for treating five
      commonly encountered conditions, including syndactyly, constriction ring
      syndrome, duplicated thumb, hypoplastic thumb, and trigger thumb. The
      accompanying videos demonstrate common and reliable surgical techniques for
      syndactyly release, duplicated thumb reconstruction, and pollicization for
      hypoplastic thumb.

PMID- 20811191
TI  - The split frontalis muscle flap endoscopically harvested for nasal soft-tissue
      defect reconstruction.

PMID- 20811192
TI  - Removal of the permanent filler polyacrylamide hydrogel (aquamid) is possible and
      easy even after several years.

PMID- 20811193
TI  - Submental flap in facial reconstructive surgery: long-term casuistry revision.

PMID- 20811194
TI  - Waste not, want not: technique to use redundant skin from elliptical skin lesion
      excision.

PMID- 20811195
TI  - Influence of the chin implant on cervicomental angle.

PMID- 20811196
TI  - Reconstruction of the posterior pharyngeal wall with a deltopectoralis flap in
      one-step surgical intervention with larynx preservation.

PMID- 20811197
TI  - Oropharyngeal reconstruction using a medial sural perforator flap.

PMID- 20811198
TI  - A simple modification to the transversus abdominis plane block provides safe and
      effective analgesia in TRAM/DIEP flap patients.

PMID- 20811199
TI  - Refinement in reduction mammaplasty: the "tubulized" inferior pedicle for
      moderate breast hypertrophy.

PMID- 20811200
TI  - Chest wall reconstruction with creation of neoribs using mesenchymal cell bone
      allograft and porcine small intestinal submucosa.

PMID- 20811201
TI  - Abdominoplasty with mesh reinforcement.

PMID- 20811202
TI  - Tissue expander reconstruction of centrifugal lipodystrophy of the abdominal
      wall.

PMID- 20811203
TI  - "Mulching" integra for glans penis reconstruction.

PMID- 20811204
TI  - Integration of the vertical medial thigh lift and monsplasty: the double-triangle
      technique.

PMID- 20811205
TI  - Treatment of chronic posttraumatic ulcers using autologous fat graft.

PMID- 20811206
TI  - Boosting blood flow: intravenous cyclizine in microsurgery.

PMID- 20811207
TI  - Intralesional injection of corticosteroids: a lesson from liposuction.

PMID- 20811208
TI  - Subcutaneous epinephrine for vasoconstriction: an evidence-based evaluation.

PMID- 20811209
TI  - The single dominant medial row perforator DIEP flap in breast reconstruction:
      three-dimensional perforasome and clinical results.
AB  - BACKGROUND: Successful outcomes with the deep inferior epigastric artery
      perforator (DIEP) flap are heavily dependent on identifying the largest
      perforators. The purpose of this study was to describe the vascular anatomy
      (location, size, zones of perfusion, and variations) of the single most dominant
      deep inferior epigastric artery perforator and to report a clinical series based
      on this flap. METHODS: Eleven abdominal flaps were harvested from fresh adult
      cadavers, and measurements were combined with clinical measurements from 16
      patients. Details such as perforator size, location, type, and zones of perfusion
      were documented for all flaps and clinical outcomes for all patients. RESULTS: A
      total of 36 flaps were dissected with an average perforator location within a 3
      cm radius of the umbilicus and an average perforator size greater than 1.8 mm.
      Computed tomographic scans of the cadaver abdominal flaps demonstrated consistent
      perfusion in zones I and II and half of zones III and IV. Clinical results showed
      partial flap necrosis in one patient and fat necrosis of less than 5 percent in
      three patients, all of which occurred in the distal portion of zone III. The deep
      inferior epigastric artery medial row perforators near the umbilicus were found
      to be the largest perforators in the entire deep inferior epigastric artery
      system and abdomen. CONCLUSIONS: The single dominant medial row perforator has a
      maximal vascularity in zones I and II, and less in zones III an IV. The authors
      recommend that half of zone III and all of zone IV be discarded to avoid the
      risks of partial flap loss and fat necrosis.

PMID- 20811210
TI  - Lymphaticovenular bypass for lymphedema management in breast cancer patients: a
      prospective study.
AB  - BACKGROUND: Lymphedema is a common and debilitating condition. Management options
      for lymphedema are limited and controversial. The purpose of this prospective
      study was to provide a preliminary analysis of lymphaticovenular bypass for the
      treatment of upper limb lymphedema in breast cancer patients. METHODS: Twenty
      patients with upper extremity lymphedema secondary to treatment of breast cancer
      underwent lymphaticovenular bypass using a "supermicrosurgical" approach. The
      mean age of the patients was 54 years, 16 patients had received preoperative
      radiation therapy, and all patients had received axillary lymph node dissection.
      The mean duration of lymphedema was 4.8 years, and the mean volume differential
      of the lymphedematous arm compared with the unaffected arm was 34 percent.
      Evaluation included qualitative assessment and quantitative volumetric analysis
      before surgery and at 1 month, 3 months, 6 months, and 1 year after the
      procedure. RESULTS: The mean number of bypasses performed per patient was 3.5
      (range, two to five), and the size of bypasses ranged from 0.3 to 0.8 mm. The
      mean operative time was 3.3 hours (range, 2 to 5 hours). Hospital stay was less
      than 24 hours for all patients. The mean follow-up time was 18 months. Nineteen
      patients (95 percent) reported symptom improvement following surgery, and 13
      patients had quantitative improvement. The mean volume differential reduction was
      29 percent at 1 month, 36 percent at 3 months, 39 percent at 6 months, and 35
      percent at 1 year. No patients experienced postoperative complications or
      lymphedema exacerbation. CONCLUSIONS: Lymphaticovenular bypass may effectively
      reduce the severity of lymphedema in breast cancer patients. Long-term analysis
      is needed.

PMID- 20811211
TI  - Discussion: Lymphaticovenular bypass for lymphedema management in breast cancer
      patients: a prospective study.

PMID- 20811212
TI  - Breast implant infections: is cefazolin enough?
AB  - BACKGROUND: Bacterial infection is a well-known risk of breast implant surgery,
      occurring in 2.0 to 2.5 percent of cosmetic cases and up to 20 percent of
      reconstructive cases. The Centers for Disease Control and Prevention recommends a
      first-generation cephalosporin for perioperative prophylaxis; however, no
      guidelines exist for the empiric treatment of established breast implant
      infections. A recent increase in methicillin-resistant Staphylococcus aureus
      infections has prompted interest in using alternative antibiotics with anti
      methicillin-resistant S. aureus activity for both prophylactic and empiric
      therapy. The goal of the present study was to assess the bacteriology and
      antibiotic susceptibility of breast implant-related infections at two tertiary
      care hospitals in the Texas Medical Center to determine whether a baseline for
      empiric therapy for breast implant infections could be established. METHODS: A
      retrospective review of patients who developed periprosthetic infections within 1
      month after breast implant placement between 2001 and 2006 was completed. One
      hundred six patients with 116 infected breasts were identified. Patients were
      included in the study only if they had documented culture data. RESULTS: Thirty
      one breasts in 26 patients met inclusion criteria. Sixty-seven percent of the
      infected breasts had S. aureus infections; of these, 68 percent were methicillin
      resistant S. aureus infections and 32 percent were methicillin-susceptible S.
      aureus infections. We noted Gram-negative rods and sterile cultures in 6 percent
      and 26 percent of breasts, respectively. CONCLUSIONS: Because of the high
      incidence of methicillin-resistant S. aureus infections in breast implant
      recipients, we believe that choosing an antibiotic with anti-methicillin
      resistant S. aureus activity is justified for empiric treatment of breast implant
      infections, until culture and sensitivity data, if obtained, become available.

PMID- 20811213
TI  - Enhancing pedicle safety in mastopexy and breast reduction procedures: the
      posteroinferomedial pedicle, retaining the medial vertical ligament of Wuringer.
AB  - BACKGROUND: Nipple necrosis, a potential postoperative complication of breast
      surgery procedures, should be avoided. Because of the great variation in the
      blood supply to the nipple, it is advisable to include as many arteries in the
      pedicle as possible. According to the literature, the perforators of the internal
      thoracic artery are the most constant and reliable sources of blood to the nipple
      areola complex. It is also supplied by the lateral thoracic artery and the
      anterior intercostal arteries. If two of the above-mentioned main vessel branches
      are included in the pedicle, the vascular supply to the breast will be more
      reliable. According to the anatomical studies of Wuringer and van Deventer, we
      can safely include the dual blood supply to the nipple-areola complex. METHODS:
      In the authors' technique, a pedicle is raised that includes the horizontal
      septum and the medial vertical ligament of the breast (i.e., inferior and
      superomedial pedicles), but with the breast tissue remaining attached to the
      pectoral fascia. The second, third, and fourth perforators of the internal
      thoracic artery are found in the medial vertical ligament, and the inferior
      mammary branches of the anterior intercostal arteries are in the horizontal
      septum. The authors have performed this technique in 106 consecutive patients
      (211 breasts) between 2001 and 2009. RESULTS: Good results regarding breast
      shape, nipple projection, and upper breast fullness were obtained. CONCLUSIONS:
      The posteroinferomedial pedicle technique is safe and versatile and can be used
      with a periareolar, vertical scar, or inverted-T skin approach. The technique is
      easy to perform and has a short learning curve.

PMID- 20811214
TI  - Paracrine interaction between adipose-derived stromal cells and cranial suture
      derived mesenchymal cells.
AB  - BACKGROUND: Adipose-derived stromal cells are a potential cell source for the
      successful healing of skeletal defects. In this study, the authors sought to
      investigate the potential for cranial suture-derived mesenchymal cells to promote
      the osteogenic differentiation of adipose-derived stromal cells. Various reports
      have previously examined the unique in vitro attributes of suture-derived
      mesenchymal cells; this study sought to extend those findings. METHODS: Suture
      derived mesenchymal cells were isolated from wild-type mice (n = 30) from both
      fusing posterofrontal and patent sagittal sutures. Cells were placed in Transwell
      inserts with human adipose-derived stromal cells (n = 5 patients) with osteogenic
      differentiation medium with or without recombinant Noggin (10 to 400 ng/ml).
      Specific gene expression of osteogenic markers and Hedgehog pathway were assayed;
      standard osteogenic assays (alkaline phosphatase and alizarin red staining) were
      performed. All assays were performed in triplicate. RESULTS: Both posterofrontal
      and sagittal suture-derived mesenchymal cells induced osteogenic differentiation
      of adipose-derived stromal cells (p < 0.05). Posterofrontal suture-derived
      mesenchymal cells induced adipose-derived stromal cell osteogenesis to a greater
      degree than sagittal suture-derived mesenchymal cells (p < 0.05). This was
      accompanied by an increase in bone morphogenetic protein expression (p < 0.05).
      Finally, recombinant Noggin mitigated the pro-osteogenic effects of co-culture
      accompanied by a reduction in Hedgehog signaling (p < 0.05). CONCLUSIONS: Suture
      derived mesenchymal cells secrete paracrine factors that induce osteogenic
      differentiation of multipotent stromal cells (human adipose-derived stromal
      cells). Cells derived from the fusing posterofrontal suture do this to a
      significantly greater degree than cells from the patent sagittal suture. Enhanced
      bone morphogenetic protein and Hedgehog signaling may underlie this paracrine
      effect.

PMID- 20811215
TI  - Depot-specific variation in the osteogenic and adipogenic potential of human
      adipose-derived stromal cells.
AB  - BACKGROUND: Adipose-derived stromal cells hold promise for use in tissue
      regeneration. However, multiple facets of their biology remain unclear. The
      authors examined the variations in osteogenesis and adipogenesis in adipose
      derived stromal cells between subcutaneous fat depots and potential molecular
      causes. METHODS: Adipose-derived stromal cells were isolated from human patients
      from subcutaneous fat depots, including arm, flank, thigh, and abdomen (n = 5
      patients). Osteogenic and adipogenic differentiation was performed (alkaline
      phosphatase, alizarin red, and oil red O staining, and quantitative real-time
      polymerase chain reaction). Co-cultures were established to assess the paracrine
      effect of human adipose-derived stromal cells on mouse osteoblasts. Finally, HOX
      gene expression was analyzed by quantitative real-time polymerase chain reaction.
      RESULTS: Subcutaneous fat depots retain markedly different osteogenic and
      adipogenic potentials. Osteogenesis was most robust in adipose-derived stromal
      cells from the flank and thigh, as compared with those from the arm and abdomen
      (p < 0.05 by all markers examined). This was accompanied by elevations of BMP4
      and BMPR1B (p < 0.05 by all markers examined). The osteogenic advantage of cells
      from the flank and thigh was again observed when analyzing the paracrine effects
      of these cells. Conversely, those cells isolated from the flank had a lesser
      ability to undergo adipogenic differentiation. Adipose-associated HOX genes were
      less expressed in flank-derived adipose-derived stromal cells. CONCLUSIONS:
      Variations exist between fat depots in terms of adipose-derived stromal cell
      osteogenic and adipogenic differentiation. Differences in HOX expression and bone
      morphogenetic protein signaling may underlie these observations. This study
      indicates that the choice of fat depot derivation of adipose-derived stromal
      cells may be an important one for future efforts in tissue engineering.

PMID- 20811216
TI  - Subclinical (biofilm) infection causes capsular contracture in a porcine model
      following augmentation mammaplasty.
AB  - BACKGROUND: Capsular contracture remains the most common complication following
      augmentation mammaplasty. The infective hypothesis implicates subclinical
      infection with biofilm in its pathogenesis. The authors developed an in vivo
      model of subclinical infection and biofilm formation to further investigate this.
      METHODS: Adult female pigs underwent augmentation mammaplasty using miniature gel
      filled implants. Staphylococcus epidermidis was inoculated into some of the
      periprosthetics as compared with control pockets, which were not inoculated.
      Implants were left in situ for 13 weeks, after which clinical assessment with the
      Baker technique was performed. Implants and capsules were then removed and
      subjected to laboratory analysis to detect biofilm. RESULTS: Fifty-one breast
      augmentations were performed in six pigs: 36 in submammary pockets inoculated
      with S. epidermidis and 15 in uninoculated pockets. Twenty-six of the 36
      inoculated implants (72.2 percent) resulted in biofilm production. Pocket
      inoculation was strongly associated with biofilm formation (p = 0.0095). The
      presence of biofilm in the inoculated pockets was also significantly associated
      with the subsequent development of capsular contracture as compared with the
      uninoculated pockets (p < 0.05). Of the 15 uninoculated pockets, seven developed
      contracture. Five of these, however, demonstrated the presence of biofilm caused
      by native porcine S. epidermidis. Of the 31 biofilm-positive specimens, 25 (80.6
      percent) developed capsular contracture. Using univariate analysis, biofilm
      formation was associated with a fourfold increased risk of developing contracture
      (odds ratio, 4.1667; 95 percent confidence interval, 1.1939 to 14.5413).
      CONCLUSION: Using this in vivo model, the authors have demonstrated a causal link
      between subclinical infection, biofilm formation, and capsular contracture.

PMID- 20811217
TI  - Discussion: Subclinical (biofilm) infection causes capsular contracture in a
      porcine model following augmentation mammaplasty.

PMID- 20811218
TI  - Discussion: Adipose tissue-derived stem cells enhance bioprosthetic mesh repair
      of ventral hernias.

PMID- 20811219
TI  - Tissue engineering in plastic surgery: a review.
AB  - SUMMARY: Novel tissue- and organ-engineering strategies are needed to address the
      growing need for replacement biological parts. Collective progress in stem cell
      technology, biomaterials, engineering, and molecular medicine has advanced the
      state of regenerative medicine, yet many hurdles to clinical translation remain.
      Plastic surgeons are in an ideal position to capitalize on emerging technologies
      and will be at the forefront of transitioning basic science research into the
      clinical reconstructive arena. This review highlights fundamental principles of
      bioengineering, recent progress in tissue-specific engineering, and future
      directions for this exciting and rapidly evolving area of medicine.

PMID- 20811220
TI  - A rapid vascular anastomosis technique for hind-limb transplantation in rats.

PMID- 20811221
TI  - The temporoparietal fascial flap is an alternative to free flaps for
      orbitomaxillary reconstruction.
AB  - BACKGROUND: The temporoparietal fascial flap is a thin, pliable, well
      vascularized, locoregional flap that can be a reasonable alternative to
      traditional free flap reconstruction, but its utility for reconstruction of
      orbitomaxillary defects is often overlooked. The authors investigated the
      rationale for and benefits of the use of this flap over free tissue transfer in a
      well-defined subset of head and neck cancer cases. METHODS: The records of all
      patients who underwent temporoparietal fascial reconstruction for
      orbitomaxillectomy between 1993 and 2008 were reviewed. Demographic data,
      preoperative plans, operative details, and outcomes were assessed to (1)
      determine the overall outcomes for the temporoparietal fascial flap and (2)
      analyze preoperative and intraoperative factors that led to the choice of this
      flap instead of the originally planned free flap. RESULTS: Nineteen patients
      (mean age, 56 years) were included in this study. Ten (53 percent) were initially
      considered for free flap reconstruction. Among them, the principal reasons for
      electing the temporoparietal fascial flap were (1) smaller-than-anticipated
      extent of resection, (2) need for coverage of implant or bone or thin prosthesis
      support, and (3) patient comorbidities. Nine resections (47 percent) involved the
      orbit alone, two (11 percent) involved the maxilla alone, and eight (42 percent)
      involved a combination of the two. Five patients (26 percent) received
      neoadjuvant radiation. Four (21 percent) experienced complications (flap failure,
      ectropion, enophthalmos with intraoral mesh extrusion, and partial skin graft
      loss). Mean follow-up time was 36 +/- 27 months. CONCLUSION: The temporoparietal
      fascial flap is a viable alternative to free flaps for orbitomaxillary defects
      when orbital resection is limited, when obturator reconstruction is desired, or
      when comorbidities preclude microvascular surgery.

PMID- 20811222
TI  - Management of complicated facial hemangiomas with beta-blocker (propranolol)
      therapy.

PMID- 20811223
TI  - Ethical considerations in the first American face transplant.
AB  - BACKGROUND: Before performing the first face transplant in the United States, the
      authors addressed several ethical considerations: subject selection, adequacy of
      informed consent, and risk-to-benefit analysis. METHODS: Destruction of the
      patient's midface, including its bony architecture, had impaired the ability of
      the authors' patient to speak, eat, smell, and socialize. These functional
      impairments and the inability of conventional reconstruction to reconstruct this
      deformity justified considering this patient for face transplantation. The
      patient's resilience in adapting to her injury, her conscientious self-care
      following her initial injury, and her ability to understand the risks and
      uncertainties of the proposed procedure were important factors in selecting her
      as a candidate for this innovation. To enhance our patient's understanding of
      this largely untried procedure, the informed consent process occurred over
      multiple encounters involving both information disclosure and assessment of
      comprehension of what the procedure involved, including its potential benefits
      and risks. The patient demonstrated not only understanding of the procedure,
      including its innovative nature and concomitant uncertainties, but also that its
      goals were consistent with her values. RESULTS: Research risk-to-benefit analysis
      involved balancing societal and subject benefits against subject risks. The
      potential benefit to society and increased knowledge of the role of face
      transplantation in facial reconstruction were substantial. The subject's benefits
      had been maximized and harms minimized through subject selection, team expertise,
      and preparation. This produced a risk-to-benefit profile in which we considered
      that the benefits sufficiently outweighed the risks to proceed with
      transplantation in this patient. CONCLUSION: Ethical considerations were
      important determinants in the decision to proceed with facial transplantation in
      this woman.

PMID- 20811225
TI  - Current tools for noninvasive objective assessment of skin scars.
AB  - BACKGROUND: Cutaneous scarring is affected by genetic, physiologic, and
      biochemical factors. These produce a continuum of scar types (i.e., keloid,
      hypertrophic, atrophic, contracted, and fine line) that can be symptomatic,
      aesthetically unsatisfactory, psychologically distressing, and functionally
      restrictive to the affected individual. Accurate scar assessment allows for
      quantification of scar evolution and management, and is key to evaluating the
      effectiveness of applied modulating therapies and treatments. Numerous objective
      instruments exist for the evaluation of different scar characteristics, but no
      consensus has been reached as to the most appropriate device. This review aims to
      explore the current range of noninvasive objective assessment tools available for
      cutaneous skin scarring, with specific emphasis on their application to research
      trials and clinical practice. METHODS: An extensive search of the literature was
      completed to assemble comprehensive data surrounding the objective assessment of
      skin scars by both validation studies and clinical trials. RESULTS: A wide range
      of tools exist to monitor cutaneous scar physical characteristics. Primarily,
      there are four parameters explored by these instruments: (1) color, including
      pigmentation and vascularity (e.g., laser Doppler); (2) surface area (e.g., three
      dimensional scanning); (3) height/depth (e.g., ultrasonography); and (4)
      pliability (e.g., tonometry). Many studies appraise single instruments in
      specific scar patient groups with subjective comparator tools. CONCLUSIONS: There
      is no overall valid and reliable noninvasive objective assessment tool for
      measurement of cutaneous skin scar characteristics. Further studies are warranted
      that compare multiple, parameter-specific instruments in a single-sample group
      and across a range of scar types.

PMID- 20811224
TI  - Poland syndrome: evaluation and treatment of the chest wall in 63 patients.
AB  - BACKGROUND: Poland syndrome is a sporadic, congenital unilateral absence of the
      sternocostal head of the pectoralis major muscle that can occur with other
      ipsilateral chest wall and limb derangements. The chest wall deficiency is
      primarily cosmetic, its incidence is unknown, male patients may be affected more
      than female patients, the right side is affected more than the left, and
      associated comorbidities may exist. Chest wall repair depends on anatomical type
      and gender. METHODS: Sixty-three patients with Poland syndrome were divided into
      two treatment groups by chest wall anatomy and gender. Surgical repair was based
      on this division. Seventy-six operations were performed by the senior author
      (A.E.S.) during a 30-year period, and long-term outcomes are presented.
      Corrective methods included use of custom-made chest wall prostheses, mammary
      prostheses, latissimus dorsi muscle transfers, transverse rectus abdominis
      musculocutaneous flaps, sternal/rib reconstruction, or a combination of methods.
      Follow-up ranged from 1 to 21 years. RESULTS: Two anatomical forms of the
      disorder are described, each with unique surgical requirements. The simple
      deformity was effectively repaired with a latissimus dorsi muscle transfer plus,
      in female patients, a sublatissimus mammary prosthesis. Repair of the complex
      deformity, in addition to the latissimus transfer, selectively included
      musculoskeletal chest wall realignment. Custom-made chest wall prostheses carried
      a higher risk of complications. CONCLUSIONS: Poland syndrome of the chest wall
      exists in two forms: the more common simple variety and a complex form (as
      originally described by Poland). Repair of the chest wall can be effectively
      tailored to these anatomical types, gender, and patient preference.

PMID- 20811226
TI  - Assessment of donor-site morbidity following rectus femoris harvest for
      infrainguinal reconstruction.
AB  - BACKGROUND: Advantages of the pedicled rectus femoris myofascial flap for groin
      wound coverage include a sufficient arc of rotation to reach the groin and
      inguinal region, a dependable vascular pedicle, and low donor-site morbidity. The
      authors aim to demonstrate the functional deficit resulting from use of the
      rectus femoris flap in groin wound reconstruction. METHODS: One hundred six
      rectus femoris flaps were performed for groin wound reconstruction over a 10-year
      period. From this cohort, consent was successfully obtained from 20 patients for
      testing of thigh function. Testing included both a subjective questionnaire
      eliciting patient assessment of postoperative thigh strength, and objective
      muscle strength testing using isometric dynamometer analysis. An age- and sex
      matched control group of 20 subjects with no operative history or known
      discrepancy of thigh strength underwent identical testing. RESULTS: : Subjects
      were tested an average of 33 months postoperatively. Dynamometer studies
      demonstrated a mean nonoperative and operative thigh peak torque of 135 ft-lb and
      104 ft-lb, respectively, or a 21 percent difference in isometric knee extensor
      strength favoring the dominant leg (p = 0.02). Similarly, the control group
      exhibited a 17 percent strength difference between both thighs (p = 0.04).
      CONCLUSIONS: Operative subjects exhibited a lower peak torque generated by the
      operative leg relative to the nonoperative leg. However, a similar difference was
      observed in the matched control cohort. Thus, there is little isolated deficit in
      quadriceps strength as a result of rectus femoris harvest.

PMID- 20811227
TI  - The hyperthermic effect of a distal volar forearm nerve block: a possible
      treatment of acute digital frostbite injuries?
AB  - BACKGROUND: The authors have observed that carpal tunnel surgery nerve blocks
      consisting of subfascial distal volar forearm injection of 10 cc of 1% lidocaine
      with epinephrine result in fingers that appear hyperemic, warm, and numb in both
      median and ulnar nerve distributions. The purposes of this study were to (1)
      determine whether forearm nerve blocks in patients undergoing carpal tunnel
      releases result in an objective increase in finger temperature, and (2) document
      the location and duration of finger anesthesia. METHODS: Thirty-nine patients
      undergoing unilateral carpal tunnel release were studied prospectively. An
      infrared thermometer was used to measure the temperature in the fingers of
      operative and nonoperative hands before and after injection of local anesthetic.
      The distal volar forearm block was performed using 10 cc of 1% lidocaine with
      1:100,000 epinephrine deep to the forearm fascia between the median and ulnar
      nerves 1 cm proximal to the wrist crease. Before and after carpal tunnel release,
      bilateral finger temperatures were measured at hourly intervals. Statistical
      analysis included a one-sample test of proportions. RESULTS: The finger
      temperature of the operative hand was significantly warmer than the unoperated
      hand over the first 2 hours after the nerve block. Seventy-four percent of
      patients had a statistically significant increase in temperature. On average, the
      nerve block lasted 6.27 hours in the median nerve distribution and 5.78 hours in
      the ulnar nerve distribution. CONCLUSIONS: Forearm nerve blocks produce a
      chemical sympathectomy that provides a significant increase in skin temperature
      as a result of vasodilatation in most patients. They also provide prolonged
      finger numbness. This could be of clinical benefit in patients with acute finger
      frostbite injuries.

PMID- 20811228
TI  - Our experience with secondary reconstruction of external rotation in obstetrical
      brachial plexus palsy.
AB  - BACKGROUND: Restoration of shoulder external rotation is very important for upper
      extremity function. The purpose of this study was to present the authors'
      experience with secondary restoration of external rotation in patients with
      obstetrical brachial plexus palsy. METHODS: From 1978 to 2002, 46 children
      underwent secondary surgery for restoration of external rotation. Outcomes were
      analyzed in relation to various factors, including the type of procedure, muscle
      transfer only versus nerve reconstruction and muscle transfer, denervation time,
      type of injury (Erb versus global palsy), and severity score. In addition, the
      effect of restoration of external rotation on the final outcome of shoulder
      abduction was assessed. RESULTS: There was significant improvement in every case
      (p < 0.01) between preoperatively and postoperatively. The overall mean
      postoperative Mallet score for the group undergoing muscle transfer only was
      3.95, whereas in the nerve reconstruction and muscle transfer group, the score
      was 3.88 (p >0.05). The resulting gain in external rotation was 99 degrees versus
      93.8 degrees. In both populations, a very significant improvement (p <0.0001) was
      identified in the final outcome of shoulder abduction (109 degrees after muscle
      transfer versus 48.3 degrees before muscle transfer, and 112 degrees
      postoperatively after neurotization and muscle transfer versus 43.8 degrees
      before any surgery). Patients with Erb palsy had a better but not significant
      result (p >0.05; p = 0.94), compared with those with global palsy in both Mallet
      score (3.77 versus 3.76) and final active external rotation (81.7 degrees versus
      77.6 degrees). CONCLUSION: Secondary surgery for the restoration of external
      rotation is a rewarding procedure, which also significantly improves the final
      outcome of shoulder abduction.

PMID- 20811229
TI  - Reconstruction of massive bone losses of the elbow with vascularized bone
      transfers.
AB  - BACKGROUND: Massive bone loss of the elbow in young patients is a complex injury.
      A series of five cases of massive loss of the elbow joint reconstructed with
      single or double vascularized bone transfers is reported. METHODS: Five patients
      with nonacute massive bone loss of the distal humerus (two cases) or distal
      humerus and proximal ulna (three cases) were reconstructed with a single (two
      cases) or double (three cases) microvascular vascularized bone transfer from the
      iliac crest, the fibula, or the scapula. Collateral ligament reconstruction was
      performed in a second stage. Follow-up was 1 to 3 years. RESULTS: All free flaps
      survived. There was one septic complication not affecting flap survival. The
      number of surgical procedures was 3.2 (range, two to five). Active range of
      motion was 86 degrees (range, 70 to 100 degrees), without significant pain and
      acceptable lateral stability. Treatment time was 7 to 13 months. CONCLUSIONS:
      Vascularized bone transfer can restore the articular gross anatomy in cases of
      massive destruction of the elbow. Midterm functional results have been favorable
      in a short series of young patients.

PMID- 20811230
TI  - Evaluation of three surgical techniques for advancement of the midface in growing
      children with syndromic craniosynostosis.
AB  - BACKGROUND: The purpose of this study was to compare clinical outcomes and 1-year
      postsurgical stability with three different techniques of Le Fort III midface
      advancement. METHODS: The records of 212 syndromic craniosynostosis patients were
      reviewed from the period 1973 to 2006. A total of 60 patients satisfied the
      inclusion criteria, and the mean age of the sample at surgery was 6.2 years. In
      group I (1977 to 1987), fixation was performed by interosseous wiring and
      intermaxillary fixation; in group II (1987 to 1996), fixation was achieved by
      only rigid plate fixation; and in group III (2000 to 2005), the patients
      underwent midface distraction with the rigid external distraction device.
      Cephalometric landmarks were identified and digitized at each of the time
      intervals (preoperatively, postoperatively, and 1 year postoperatively). RESULTS:
      The mean advancement measured at point A in group I averaged 9.7 mm; in group II,
      it was 10.6 mm; and in group 3, it was 16.1 mm. There was no statistically
      significant difference in the amount of advancement between groups I and II.
      However, when groups I and II were compared with group III, there was a
      statistically significant difference (p < 0.05). No statistical significance was
      noted within and between all three groups at 1-year follow-up. CONCLUSIONS:
      Significantly larger midface advancement was achieved with rigid external
      distraction (group III) compared with classic Le Fort III midface advancement
      with wire (group I) or plate (group III) fixation. At 1 year after surgery, the
      three groups showed relative stability of the advanced midface segment.

PMID- 20811231
TI  - Use of distraction osteogenesis to change endocranial morphology in unilateral
      coronal craniosynostosis patients.
AB  - BACKGROUND: The endocranial morphology of the skull base is an important factor
      in determining craniofacial asymmetry. Moreover, although the patency of cranial
      suture would be the first determining factor, unicoronal, unilambdoid synostosis
      and deformational plagiocephaly can also be differentiated by means of axis
      angulation of anterior and posterior cranial fossa. These findings indicate the
      importance of endocranial morphology in craniofacial asymmetry. The authors
      hypothesized that distraction of the skull base might cause stress on the skull
      base that could modify skull base angulation deformities. METHODS: This study
      compared the distraction technique with traditional bone repositioning techniques
      for remodeling skull base axis deformities in synostotic plagiocephaly patients.
      The study recruited 19 unicoronal craniosynostotic patients, of whom seven
      underwent distraction treatment and 12 underwent traditional bone graft
      treatment. RESULTS: The authors found that both approaches resulted in successful
      outcomes in terms of exocranial morphology correction, but that the distraction
      technique may offer advantages over traditional methods. Moreover, the authors
      found that distraction did modify the skull base angulation. Distraction created
      more changes in the endocranial morphology. The average correction of skull base
      angulation with distraction was from 164.6 to 174.3 degrees, whereas the
      correction for the traditional technique was from 165.2 to 166.2 degrees. The
      amount of change in skull base axis was statistically significant according to
      the Mann-Whitney test (p < 0.001), but the change in cranial index of asymmetry
      was not (p = 0.363). CONCLUSION: The skull base axis in synostotic plagiocephaly,
      which is composed of the anterior and posterior cranial fossa, underwent greater
      correction using the distraction method.

PMID- 20811232
TI  - Biomechanical considerations for distraction of the monobloc, Le Fort III, and Le
      Fort I segments.
AB  - BACKGROUND: Distraction osteogenesis is effective for correction of severe
      maxillary and midface hypoplasia. The vectors controlling the segment to be moved
      must be planned. This requires knowledge of the physical characteristics of the
      osteotomized bone segment, including the location of the center of mass (free
      body) and the center of resistance (restrained body). The purpose of this study
      was to determine the center of mass of the osteotomized monobloc, Le Fort III,
      and Le Fort I bone segments. METHODS: A dry human skull was used to sequentially
      isolate three bone segments: monobloc, Le Fort III, and Le Fort I. Each segment
      was suspended from three different points, and digital photographs were obtained
      from each suspension. The photographs were digitally superimposed. The center of
      mass was determined by calculating the intersection of the suspension lines.
      RESULTS: The center of mass for the monobloc segment was located at a point 43.5
      percent of the total height from the occlusal plane to the superior edge of the
      frontal bone supraorbital osteotomy. For the Le Fort III, it was located 38
      percent of the total height from the occlusal plane to the superior edge of the
      osteotomized base of the nasal bones. For the Le Fort I, it was 53 percent of the
      total height from the occlusal plane to the superior edge of the osteotomized
      maxillary bone. CONCLUSION: Knowledge of the location of the center of mass in
      the monobloc, Le Fort III, and Le Fort I segments provides a starting point for
      the clinician when planning vectors for advancement with distraction.

PMID- 20811233
TI  - Myotomy of the levator labii superioris muscle and lip repositioning: a combined
      approach for the correction of gummy smile.
AB  - BACKGROUND: Treatment of excessive gingival display usually involves procedures
      such as Le Fort impaction or maxillary gingivectomies. The authors propose an
      alternative technique that reduces the muscular function of the elevator of the
      upper lip muscle and repositioning of the upper lip. METHODS: Fourteen female
      patients with excessive gingival exposure were operated on between February of
      2008 and March of 2009. They were filmed before and at least 6 months after the
      procedure. They were asked to perform their fullest smile, and the maximum
      gingival exposures were measured and analyzed using ImageJ software. Patients
      were operated on under local anesthesia. Their gingival mucosa was freed from the
      maxilla using a periosteum elevator. Skin and subcutaneous tissue were dissected
      bluntly from the underlying musculature of the upper lip. A frenuloplasty was
      performed to lengthen the upper lip. Both levator labii superioris muscles were
      dissected and divided. RESULTS: The postoperative course was uneventful in all of
      the patients. The mean gingival exposure before surgery was 5.22 +/- 1.48 mm; 6
      months after surgery, it was 1.91 +/- 1.50 mm. The mean gingival exposure
      reduction was 3.31 +/- 1.05 mm (p < 0.001), ranging from 1.59 to 4.83 mm.
      CONCLUSION: This study shows that the proposed technique was efficient in
      reducing the amount of exposed gum during smile in all patients in this series.

PMID- 20811234
TI  - Value-based cleft lip-cleft palate care: a progress report.
AB  - BACKGROUND: The health care debate in the United States centers on a concept that
      is fundamental to any service-based profession yet minimally integrated into the
      health care community: value creation. Value in health care has been defined as
      outcome achieved per dollar spent, and focuses on the patient. Many of the new
      strategies proposed to restructure health care delivery in the United States aim
      to study and improve both components of this equation. Indeed, it is a near
      guarantee that providers will soon be responsible for reporting their outcomes
      and resource use and will be benchmarked by these metrics. In addition, patients
      have a right to understand the value they receive from their care providers.
      METHODS: In this report, the authors evaluate the current state of preparedness
      for the assessment of value in care delivery in the field of cleft lip-cleft
      palate based on literature review. RESULTS: There has been important progress in
      the definition and assessment of basic outcomes in cleft lip-cleft palate care,
      largely through formation of intercenter collaborations. However, many
      fundamental challenges face the cleft community, especially in North America.
      Standardization of data collection and outcomes measurement and reporting are
      particularly lacking. In addition, few data exist regarding the cost of cleft
      care. CONCLUSIONS: The weight of the evidence reveals that the cleft community is
      not prepared to assess, and thus improve, the value offered to patients. The
      authors address key challenges and outline future directions.

PMID- 20811235
TI  - Discussion: A 26-year experience with vest-over-pants technique platysmarrhaphy.

PMID- 20811236
TI  - Analysis of nasal periosteum and nasofrontal suture with clinical implications
      for dorsal nasal augmentation.
AB  - BACKGROUND: Subperiosteal placement of nasal implants has been performed widely
      for dorsal nasal augmentation in Asia. The authors introduced anatomical and
      biomechanical studies to investigate the influence of the periosteum on the
      subperiosteal technique. METHODS: Nasal periosteum on 20 cadavers was
      investigated by hematoxylin and eosin staining and biomechanical methods. Nasal
      profiles (n = 160) and motility testing (n = 1317) were used to analyze patients
      who underwent augmentation rhinoplasty between 2003 and 2008. An alternative high
      split subperiosteal technique was developed for higher placement of the nasal
      implant. RESULTS: In the cadaver study, the authors discovered that the
      periosteum and bone were bound together by Sharpey's fibers below the nasion (1.3
      +/- 0.6 mm) that penetrated into the nasofrontal suture. The nasal periosteum
      above the nasofrontal suture (1.77 +/- 0.19 mm) was thicker than the one below
      the suture (0.83 +/- 0.15 mm) (p < 0.001). Men had relatively thicker periosteum
      (1.41 +/- 0.49 mm) compared with women (1.18 +/- 0.5 mm), and the difference was
      statistically significant (p < 0.001). Motility testing for clinical cases
      revealed that there was a higher percentage of the mobilized implant in women
      than in men (p = 0.042). When the subperiosteal technique was compared with the
      subcutaneous technique, analysis of the Poisson ratio for the periosteum (0.33 +/
      0.02) indicated greater strength than in the subcutaneous tissue (0.45 +/-
      0.02). The alternative high-split subperiosteal technique significantly shortened
      the radix-to-glabella distance, increased the radix height, and made the
      nasofrontal angle more obtuse than the conventional subperiosteal technique (p <
      0.001, p < 0.001, and p = 0.02, respectively). CONCLUSION: Analysis of the nasal
      periosteum provided scientific support for using the subperiosteal technique in
      dorsal nasal augmentation.

PMID- 20811237
TI  - A new crease fixation technique for double eyelidplasty using mini-flaps derived
      from pretarsal levator tissues.
AB  - BACKGROUND: Most double eyelid operations focus on using a levator insertion into
      the upper eyelid skin that induces adhesion. Although incision method provides a
      significant supratarsal fold, it has the disadvantage of causing a visible
      depression or scarring when eyes are closed in downward gaze. METHODS: The
      authors elevated multiple comblike mini-flaps from upper eyelid pretarsal levator
      tissues under loupe magnification. Flap bases were anchored on the tarsus using 7
      0 nylon sutures, and distal flap portions were pulled out to the skin through a
      separate incision line and then interposed between edges of orbicularis muscle
      using absorbable microsutures to achieve a complete myocutaneous layer-by-layer
      repair. RESULTS: Five hundred twenty-two double eyelidplasties were performed by
      the senior surgeon (Y.C.) using the described miniflap method. Patients were
      followed for 6 to 38 months (mean, 26 months). Seven palpebral fold failures were
      encountered, especially on the medial side, and 12 cases of fold asymmetry
      occurred because of inappropriate anchoring of miniflaps; all 12 were revised
      secondarily. No granuloma formation or scar hypertrophy occurred on upper lids.
      Although mild erythematous skin changes inevitably occurred during the early
      postoperative period, patients were satisfied with the palpebral folds, which
      showed no scars during downward gaze at 2 years postoperatively. CONCLUSIONS: The
      authors introduce a modified double eyelidplasty involving the interposition of
      multiple comblike mini-flaps derived from the pretarsal levator tissue of the
      upper eyelid. The procedure not only allows clean repair of the upper eyelid
      without disrupting tissue layer continuity but also enables double eyelidplasty
      with minimal scar formation.

PMID- 20811238
TI  - Anatomy of the transversus nuchae muscle and its relationship with the
      superficial musculoaponeurotic system.
AB  - BACKGROUND: Previous studies have proved the existence of muscle fibers in the
      superficial musculoaponeurotic system (SMAS) of the parotid and masseter region;
      however, no studies have investigated the origination of the muscle fibers in the
      SMAS. Theoretically speaking, the muscle fibers within the SMAS in the parotid
      and masseter region might originate from a certain muscle with a definite origin
      and insertion. Based on this hypothesis, the authors' study investigated the
      origination of the muscle fibers in the SMAS of the parotid and masseter region
      to provide anatomical evidence that can improve our understanding of the SMAS.
      METHODS: An anatomical study was performed on 20 halves of seven fixed and three
      fresh adult cadavers (seven male and three female cadavers). A traditional
      bilateral face-lift incision was designed in each cadaver, and the muscle fibers
      within the SMAS in the parotid and masseter region, along with the origin and
      insertion, were investigated, dissected, analyzed, and photographed. RESULTS: The
      transversus nuchae muscle can be divided into two sections according to the
      origin of its tendons. The muscular fasciculi of the two sections run
      transversely across the sternocleidomastoid muscle, insert into the superficial
      fascia above the parotidomasseteric fascia, and terminate in the zygomatic
      region. The muscle fibers within the SMAS in the parotid and masseter region come
      from the transversus nuchae muscle. CONCLUSIONS: The authors' study first
      investigated the transversus nuchae muscle combined with the SMAS and clarified
      the issue that has been neglected by previous studies for more than 30 years. The
      authors hope this will unify their understanding of the SMAS and offer plastic
      surgeons and readers a brief insight into the SMAS.

PMID- 20811239
TI  - Refinements in abdominoplasty: a critical outcomes analysis over a 20-year
      period.
AB  - BACKGROUND: The use of liposuction combined with abdominoplasty has been
      controversial. The combination of techniques has been associated with an
      increased rate of venous thromboembolism and wound-healing complications. Through
      improvements in venous thromboembolism prophylaxis, refinements in liposuction
      techniques, and an understanding of anatomy, this cumulative risk has decreased,
      although the negative stigmata persist. This study describes the evolution of
      abdominal body contouring through a critical review of a single surgeon's 20-year
      experience with abdominoplasty. This clinical outcome analysis will highlight the
      significant contributions that have led to the improvement in the safety and
      efficacy of this technique. METHODS: A retrospective review of patients
      undergoing abdominoplasty procedures was performed. Patient demographics and
      procedural information, including postoperative course and complications, were
      recorded. Preoperative and postoperative photographs were scored by blinded
      evaluators for aesthetic result and scar quality. RESULTS: Two hundred fifty
      patients undergoing abdominoplasty from 1987 to 2007 were included in the study.
      The use of a "superwet" liposuction technique in combination with abdominoplasty
      significantly decreased intraoperative blood loss (p < 0.04) and length of
      hospital stay (p < 0.05). Liposuction volume and region had no significant effect
      on abdominoplasty outcome, although refinements in operative technique, including
      abdominal and flank ultrasound-assisted liposuction, high superior tension, and
      limited abdominal undermining, did improve the postoperative aesthetic score.
      Venous thromboembolic events significantly decreased with aggressive venous
      thromboembolism prophylaxis (p < 0.001). CONCLUSIONS: The technical evolution of
      a single surgeon's 20-year experience demonstrates that liposuction can be safely
      and effectively combined with abdominoplasty. Preoperative trunk analysis,
      intraoperative surgical refinements including superwet technique and ultrasound
      assisted liposuction, and perioperative venous thromboembolism prophylaxis
      significantly improve the outcome of abdominoplasty.

PMID- 20811240
TI  - Breast reshaping following massive weight loss: principles and techniques.
AB  - SUMMARY: Management of the breast following massive weight loss for both
      reconstructive and aesthetic reasons poses unique challenges that are often
      inadequately addressed with traditional techniques. The breast mound is often
      unstable and deflated, with a loose inelastic skin envelope and ill-defined
      boundaries that blend into similar lateral chest wall, arm, and upper abdominal
      contour irregularities. Because this has become more common recently with the
      increasing prevalence of massive weight loss patients desiring body contouring,
      the purpose of this review was to discuss modifications to traditional breast
      techniques that have been proposed for these patients. It has become apparent
      that mammaplasty techniques in the massive weight loss patient should rely more
      on extensive glandular manipulation for shape preservation rather than relying on
      the skin envelope for shaping. Such techniques include parenchymal plication,
      suspension, and autoaugmentation. This will improve the likelihood of maintained
      shape and symmetry in an otherwise difficult patient population.

PMID- 20811241
TI  - A systematic review of the relationship between plastic surgery and the medical
      industry.
AB  - BACKGROUND: The nature and extent of medicine's relationship with the medical
      industry is currently a heated issue in medicine. Although the ethical
      implications of this relationship have been widely discussed in medical journals
      and the popular media, it is unknown how the current interest in industry issues
      has affected plastic surgery. The aim of this systematic review was to
      characterize the literature of the past two decades that examines plastic
      surgery's relationship with the medical industry. METHODS: Three medical
      databases were searched using plastic surgery and industry-related search terms.
      The quality of selected articles was assessed by two reviewers. The specific data
      abstracted included the venue of the industry interaction discussed within the
      article: (1) physician education programs, (2) research partnerships, and (3)
      clinical settings. Within each of these categories, a comprehensive taxonomy was
      created to categorize the thematic content of the articles' discussions. RESULTS:
      Of the 465 articles gleaned by the search, 21 met the inclusion and exclusion
      criteria and were included in the final review. All 21 articles were of a review
      or editorial nature, and the majority (57 percent) discussed the nature or
      effects of industry's presence within the clinical setting. CONCLUSIONS: This
      systematic review revealed the literature's cursory analysis of plastic surgery's
      relationship with the medical industry. This project highlighted the need for
      plastic surgery to examine the ethical implications of industry's support and
      engagement within the field. Improving this literature is necessary for plastic
      surgeons to understand and adhere to current standards on acceptable practices.

PMID- 20811242
TI  - So you want to be an innovator?

PMID- 20811246
TI  - Eyelid and periorbital necrotizing fasciitis as an early devastating complication
      of blepharoplasty.

PMID- 20811247
TI  - Nasal dorsal augmentation with freeze-dried allograft bone.

PMID- 20811249
TI  - A novel cleft rhinoplasty procedure combining an open rhinoplasty with the
      Dibbell and Tajima techniques.

PMID- 20811251
TI  - Breast reconstruction and lymphedema.

PMID- 20811254
TI  - AlloDerm performance in the setting of prosthetic breast surgery, infection, and
      irradiation.

PMID- 20811255
TI  - Techniques to reduce seroma and infection in acellular dermis-assisted prosthetic
      breast reconstruction.

PMID- 20811256
TI  - The sensate medial dorsal intercostal artery perforator flap as an option for
      treatment of dorsal cervicothoracic midline defects.

PMID- 20811259
TI  - Lymphedematous arm as donor site for radial forearm free flap in thoracic
      reconstruction.

PMID- 20811260
TI  - The diminishing presence of plastic surgeons in hand surgery: a critical
      analysis.

PMID- 20811262
TI  - The diminishing presence of plastic surgeons in hand surgery.

PMID- 20811263
TI  - The versatility of the adipofascial anterolateral flap.

PMID- 20811265
TI  - The most current algorithms for the treatment and prevention of hypertrophic
      scars and keloids.

PMID- 20811268
TI  - Fractality and a wavelet-chaos-methodology for EEG-based diagnosis of Alzheimer
      disease.
AB  - Recently the senior author and his associates developed a spatiotemporal wavelet
      chaos methodology for the analysis of electroencephalograms (EEGs) and their
      subbands for discovering potential markers of abnormality in Alzheimer disease
      (AD). In this study, fractal dimension (FD) is used for the evaluation of the
      dynamical changes in the AD brain. The approach presented in this study is based
      on the research ideology that nonlinear features, such as FD, may not show
      significant differences between the AD and the control groups in the band-limited
      EEG, but may manifest in certain subbands. First, 2 different FD algorithms for
      computing the fractality of EEGs are investigated and their efficacy for yielding
      potential mathematical markers of AD is compared. They are Katz FD (KFD) and
      Higuchi FD. Significant features in different loci and different EEG subbands or
      band-limited EEG for discrimination of the AD and the control groups are
      determined by analysis of variation. The most discriminative FD and the
      corresponding loci and EEG subbands for discriminating between AD and healthy
      EEGs are discovered. As KFD of all loci in the beta subband showed very high
      ability (P value <0.001) in discriminating between the groups, all KFDs are
      abstracted in 1 global KFD by averaging across loci in each of the 2 eyes-closed
      and eyes-open conditions. This leads to a more robust classification in terms of
      common variation of electrode positions than a classification based on separate
      KFDs of certain loci. Finally, based on the 2 global features separately and
      together, linear discriminant analysis is used to classify EEGs of AD and elderly
      normal patients. A high accuracy of 99.3% was obtained for the diagnosis of the
      AD based on the global KFD in the beta-band of the eyes-closed condition with a
      sensitivity of 100% and a specificity of 97.8%.

PMID- 20811270
TI  - Oxidative stress increased in healthcare workers working 24-hour on-call shifts.
AB  - INTRODUCTION: Long work hours, night shifts, stressful situations and
      insufficient social support increase levels of anxiety and depression and
      decrease motivation to perform among healthcare professionals. In this study, we
      evaluated oxidative stress levels in medical residents working 24-hour on-call
      shifts, and in nurses, relative to non-healthcare hospital staff in sedentary
      positions. We also measured serum prolidase activity, a measure of collagen
      turnover, as an objective proxy for level of physical activity. METHODS: Fifty
      five male and 15 female medical residents on 24-hour, in-house, on-call duty, and
      45 nurses and 30 (15 male/15 female) non-healthcare staff working 8-hour shifts
      were recruited. All were healthy nonsmokers. Parameters of oxidative stress and
      serum prolidase activity were measured twice for each subject, upon arising at 8
      am after an overnight fast; and then again near the end of the work shift, or
      after 16 hours of consecutive work (at 12 pm) for residents. RESULTS: After hours
      of continuous work, serum total oxidative status and the oxidative stress index
      increased significantly, whereas total antioxidant status decreased (all P <
      0.0001) in healthcare staff (nurses, male and female residents). All these
      variables remained virtually unchanged in non-healthcare staff. Similarly, serum
      prolidase activity increased in healthcare staff (P < 0.0001), but failed to
      increase statistically in non-healthcare staff. CONCLUSIONS: Healthcare workers
      suffer increased oxidative stress after prolonged work hours, especially while
      still on duty. Possible mechanisms for this include increased workload and,
      perhaps, psychological stress as well. However, long-term studies are needed to
      clarify the effects of sustained exposure to oxidative stress.

PMID- 20811269
TI  - Is phonological-lexical representation preserved in moderate stage Alzheimer
      disease? Evidence from the efficacy of Korean syllabic cues.
AB  - Patients with Alzheimer disease (AD) usually experience naming difficulty due to
      storage and access problems in phonological-lexical representation. Investigating
      naming response patterns followed by cueing may help us to understand the
      underlying mechanism of naming deficits in AD. A total of 221 patients with mild
      cognitive impairment and AD [Clinical Dementia Rating (CDR) 0.5, 1, 2] were
      included as subjects. Sixty items of the Korean version of the Boston Naming Test
      were given, and upon failure, semantic/syllabic cues were verbally presented.
      From the results, even in the CDR 2 group, which is considered to be a moderate
      stage of AD, syllabic cues significantly facilitated correct responses. Our
      findings are in contrast with previous studies conducted with English-speaking
      patients, which reported that phonological-lexical representation may have been
      disrupted in the moderate stage of AD, and that none of the cues facilitated
      correct word retrieval. The difference may be ascribed to the fact that direct
      access to the phonological-lexical representation via syllabic cues was possible
      in the confrontation naming task performed by the Korean patients. It can be
      concluded that phonological-lexical representation in moderate stage Korean AD
      might be partially preserved because syllabic cues in AD patients were effective
      in facilitating target words. 

PMID- 20811271
TI  - The different photoplethysmographic patterns can help to distinguish patients
      with primary and sclerodermic Raynaud phenomenon.
AB  - INTRODUCTION: The aim of this study is to investigate pulsatility of digital
      arteries of hands by means of photoplethysmography (PPG) in patients with primary
      Raynaud phenomenon (PRP) and systemic sclerosis (SSc) and to compare the results
      with those obtained in healthy controls. METHODS: One hundred five patients with
      SSc, 96 patients with PRP and 85 healthy controls were recruited in this study.
      Nailfold videocapillaroscopy and PPG were performed in healthy controls and
      patients. In patients with SSc, the capillaroscopic pattern was classified as
      early, active and late group pattern. A baseline PPG was recorded simultaneously
      in all 10 fingers of the hands. The photoplethysmographic curves were evaluated
      for morphology and amplitude of sphygmic wave. RESULTS: In healthy controls
      group, PPG shows the presence of photoplethysmographic homogeneous pattern and
      high mean value of sphygmic wave amplitude. In PRP group, PPG demonstrates
      homogeneous photoplethysmographic pattern and low mean value of sphygmic wave
      amplitude. Finally, in the SSc group, photoplethysmographic pattern is
      dyshomogeneous, and the mean value of sphygmic wave amplitude is intermediate
      between the other 2 groups. The PPG findings are different in the 3
      capillaroscopic groups of patients with SSc and 2 subsets of disease. CONCLUSION:
      PPG represents a technique noninvasive to evaluate simultaneously in all 10
      fingers of hands digital arteries pulsatility. PPG improves the evaluation of
      vascular damage in patients with primary and sclerodermic RP.

PMID- 20811272
TI  - Respiratory syncytial virus infection and risk of acute myocardial infarction.
AB  - INTRODUCTION: Increasing evidences have shown that pathogens may promote
      atherosclerosis and trigger acute myocardial infarction (AMI). There is no report
      on the association between respiratory syncytial virus (RSV) infection and AMI.
      The case-control study was used to assess the association of previous RSV
      infection and acute myocardial infarction. METHODS: AMI cases and non-AMI
      controls were recruited from patients at a large teaching hospital in Harbin,
      China, during October 1, 2005, to March 31, 2006, and October 1, 2006, to March
      31, 2007. Questionnaire survey was conducted to collect information on
      demographic characteristics and heart disease risk factors. Fasting blood sample
      was obtained to measure immunoglobulin G antibodies to RSV, Cytomegalovirus,
      herpes simplex virus type-1 and type-2, adenovirus, Rubella virus, Chlamydia
      pneumoniae and Helicobacter pylori and to measure the level of cholesterol,
      fasting serum glucose, triglycerides and high-sensitivity C-reactive protein.
      RESULTS: AMI group had more smokers than controls (56.9% versus 18.0%) and were
      more likely to have positive immunoglobulin G antibodies to RSV (OR, 6.2; 95% CI,
      3.5-10.7; P < 0.001). After adjustment for potential confounding variables, the
      association between RSV and AMI remained (adjusted odds ratio, 11.1; 95%
      confidence interval, 3.3-29.5). CONCLUSIONS: Our study supported the hypothesis
      that the previous RSV infection was associated with AMI. This indicates that
      prevention and proper treatment of RSV infection are of great clinical importance
      for the reduction of AMI risk.

PMID- 20811273
TI  - Clinical features and outcome of community-acquired bacterial meningitis in adult
      patients with liver cirrhosis.
AB  - INTRODUCTION: This study aimed to analyze the clinical features, causative
      pathogens and therapeutic outcomes of bacterial meningitis in patients with liver
      cirrhosis. METHODS: Adult cirrhotic patients with community-acquired bacterial
      meningitis were evaluated. Clinical data were collected over a 22-year period.
      For comparison, the clinical features and therapeutic outcomes between patients
      with and without liver cirrhosis were analyzed. RESULTS: Liver cirrhosis
      accounted for 11% (25/217) of the predisposing factors. Significant statistical
      analysis between the 2 groups (patients with and without liver cirrhosis)
      included median Glasgow Coma Scale score at presentation, presence of seizure,
      bacteremia and septic shock. The mean duration between arrival at the emergency
      room and confirmed diagnosis of bacterial meningitis was 39 hours (range, 2-240
      hours). Ten (10/25, 40%) were initially diagnosed with bacterial meningitis, and
      6 (6/25, 24%) were initially suggested as having infection of unknown origin. In
      this study, Klebsiella pneumoniae was the most frequent causative pathogen in
      patients with liver cirrhosis. The overall case fatality rates for patients with
      and without liver cirrhosis were 38.5% (74/192) and 64% (16/25), respectively.
      CONCLUSIONS: Patients with liver cirrhosis have a more fulminant course with a
      higher prevalence of disturbed consciousness, bacteremia, seizure and shock.
      Diagnosis and effective treatment ARE often delayed, resulting in high overall
      mortality. When patients with liver cirrhosis develop disturbed consciousness,
      seizures and septicemia, immediate neuroimaging and cerebrospinal fluid studies
      should be undertaken to determine bacterial meningitis. Early diagnosis and
      treatment are essential for survival.

PMID- 20811275
TI  - Detection of HCV RNA in the peripheral blood mononuclear cells of serum HCV RNA
      negative Egyptian patients under interferon treatment.
AB  - INTRODUCTION: Despite recent success after the introduction of combination
      therapy with interferon (IFN)-alpha and ribavirin, approximately 60% of patients
      with hepatitis C virus (HCV) genotype 4 fail to respond. Resistance to antiviral
      therapy remains a serious problem in the management of chronic hepatitis C. In
      most patients, HCV RNA could be detected in peripheral blood mononuclear cell
      (PBMC). OBJECTIVE: The authors aimed to investigate the predictive value of HCV
      RNA in PBMC of patients with chronic hepatitis C after IFN treatment, which may
      act as the source of HCV reinfection of hepatic cells. METHODS: Seventy patients
      with chronic hepatitis C were treated with IFN plus ribavirin for 48 weeks; they
      all achieved clearance of HCV RNA from serum. At the end of treatment, PBMC and
      serum were examined by real-time polymerase chain reaction for detection of HCV
      RNA. Six months later, HCV RNA in serum was monitored to detect sustained
      virologic response. RESULTS: : Analysis revealed the presence of detectable HCV
      RNA in the PBMC of 27% of patients despite clearance of serum HCV RNA. During
      follow-up, 80% of the patients who became serum HCV positive 6 months after the
      end of treatment had detectable level of HCV RNA in PBMC at the end of treatment.
      CONCLUSIONS: The absence of HCV in the serum of patients by the end of treatment
      does not exclude future viremia. The patient might still be a source of infection
      to others. It is strongly encouraged to test for HCV in PBMC to detect lack of
      response to treatment and persisting infection.

PMID- 20811274
TI  - Functional CCR5 receptor protects patients with arthritis from high synovial
      burden of infecting Chlamydia trachomatis.
AB  - INTRODUCTION: The CCR5 chemokine receptor occurs in a wild-type (wt) and a
      nonfunctional deleted form (Delta32). Reports suggested that Chlamydia-induced
      reproductive tract pathology is attenuated in women bearing Delta32. The authors
      asked whether the mutation affects synovial prevalence and burden of Chlamydia
      trachomatis. METHODS: Polymerase chain reaction (PCR) defined CCR5 genotype in
      synovial tissue DNA from 218 individuals: 21 controls, 110 with reactive
      arthritis (ReA), 83 with undifferentiated oligoarthritis (UO), 4 with
      osteoarthritis (OA). Disease durations were 0.5 to 21 years. Additional PCR
      assays defined the presence of C trachomatis DNA. Bacterial load was assessed by
      real-time PCR in selected samples. RESULTS: Five controls were wt/Delta32, 16
      were wt/wt; 2 of 21 controls (both wt/wt) were PCR positive for C trachomatis.
      Eighty-five (44%) patients with arthritis were PCR positive for C trachomatis (69
      ReA and 16 UO). For patients with ReA, 14 (13%) had wt/Delta32, 10 (71%) of whom
      were PCR positive. Nineteen patients with UO (23%) were wt/Delta32, with 1 (1%)
      PCR positive. No differences existed for gender or other factors. One patient
      with OA had wt/Delta32. In ReA and UO samples, wt/Delta32 heterozygotes had a 5-
      to 10-fold higher bacterial burden than did wt/wt patients (P = 0.03), regardless
      of diagnosis. CONCLUSION: These results indicate that the wt/wt genotype is
      associated with attenuated synovial bacterial load compared with loads in
      wt/Delta32 patients. Although no alleles other than Delta32 were assessed, our
      data suggest that this allele provides little/no protection from ReA in patients
      infected with Chlamydia- but it may provide some protection in patients with UO.
      The basis of this possible differential effect of CCR5 genotype is under study.

PMID- 20811276
TI  - Effects of zonisamide in the treatment of alcohol dependence.
AB  - OBJECTIVE: Anticonvulsant drugs have been used in the treatment of alcohol
      dependence. The purpose of the present study was to evaluate tolerance and safety
      of zonisamide in a sample of patients presenting alcohol dependence. METHODS:
      Open-label zonisamide was examined in 22 outpatients with Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition alcohol dependence.
      Zonisamide was started at a dose of 50 mg/d and titrated to a maximun dose of 300
      mg/d. Subjects received a baseline evaluation including Structured Clinical
      Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition and the Severity of Alcohol Dependence Scale. Alcohol craving and alcohol
      consumption were assessed at weeks 2, 4, 6, 8, 10, and 12. The concentration of
      gamma-glutamyltransferase was used as an indirect measure of alcohol consumption.
      RESULTS: Significant improvement was observed in visual analog scale for craving
      severity scores, weekly drink consumption, and gamma-glutamyltransferase.
      Zonisamide was well tolerated, with only a dropout due to adverse events.
      CONCLUSIONS: Zonisamide is safe and well tolerated in this sample and associated
      with improvement in alcohol craving and alcohol consumption. A placebo-controlled
      study would be of interest.

PMID- 20811277
TI  - Bevacizumab: current updates in treatment.
AB  - PURPOSE OF REVIEW: Drugs targeting angiogenesis are rapidly being incorporated
      into cancer treatment regimens. Bevacizumab was the first antiangiogenesis agent
      to gain approval by the Food and Drug Administration and is now approved for use
      in five tumor types. This brief review highlights important recent advances in
      our understanding of bevacizumab and the patient populations in whom it may be
      most beneficial. RECENT FINDINGS: Results from early studies that led to approval
      of bevacizumab for use in metastatic colorectal cancer and metastatic lung cancer
      have been confirmed. Although bevacizumab does not appear to prolong disease-free
      survival in the adjuvant treatment of colorectal cancer, phase II results in the
      neoadjuvant treatment of colorectal cancer and breast cancer are encouraging. It
      may also have a role in maintenance therapy of colorectal cancer and nonsmall
      cell lung cancer. Bevacizumab is an important agent in the treatment of recurrent
      glioma. Although the safety profile of bevacizumab in combination with cytotoxic
      agents has not changed significantly, there may be excess risk associated with
      combined angiogenesis blockade. SUMMARY: Bevacizumab has efficacy in a wide
      variety of cancers and fairly predictable toxicities. In addition to further
      exploration of the benefits of bevacizumab in other tumor types, future research
      should focus on integration of biomarkers into patient selection and treatment.

PMID- 20811278
TI  - Front-line management of diffuse large B cell lymphoma.
AB  - PURPOSE OF REVIEW: During the past decade, we have witnessed major advances in
      the management of diffuse large B cell lymphoma. With modern treatment regimens,
      approximately 75% of patients with this disorder can be cured in contrast with
      40% in the past. The purpose of this review is to discuss the pertinent advances
      and to highlight areas of consensus and controversy. RECENT FINDINGS: The
      combination of rituximab with cyclophosphamide, doxorubicin vincristine, and
      prednisone (CHOP) ('R-CHOP regimen') constituted the first major advance in this
      field. This regimen is associated with superior survival as compared with the
      same regimen without rituximab, regardless of the patient's age and other
      factors. This was quickly followed by the introduction of the dose dense 'CHOP
      14' regimen given every 14 instead of every 21 days. CHOP-14 is superior to CHOP
      given every 21 days. SUMMARY: Areas of consensus include: use of rituximab with
      CHOP as part of front-line treatment, lack of effectiveness of maintenance
      rituximab in contrast to follicular low-grade lymphomas is also acknowledged, and
      dose-dense R-CHOP-14 regimen has not been compared head to head with R-CHOP-21.
      For that reason, there is no generalized consensus as to its effectiveness.
      Opportunities for further improvements in management based on new biological
      insights are discussed.

PMID- 20811280
TI  - Ocular manifestations of systemic disease: ocular parasitosis.
AB  - PURPOSE OF REVIEW: To highlight recent advances in basic research, diagnostic as
      well as therapeutic advances in ocular parasitosis and to evaluate their
      application in medical practice. RECENT FINDINGS: Knowledge relating to
      immunoreactivity in ocular parasitology has grown impressively in past few years.
      The outcome of infection is the result of a set of interactions involving host
      and parasite genetic background, environmental and social factors.
      Immunopathogenesis of parasite-mediated host cell lysis is better understood.
      Studies on newer drugs with cophylogenetic techniques are in horizon. There are
      success stories on control of transmission in some countries. SUMMARY: Much has
      been achieved; however, much more effort is needed in the area of translational
      research from bench to bedside. There is a need to enhance the awareness of risk
      factors of parasitic diseases in the population. Newer molecular diagnostic
      techniques need to be standardized for field application. Steps needed to be
      taken by the ophthalmologist when a parasite is seen in ocular tissues including
      identification, search for systemic involvement, treatment for elimination and
      sequelae and public health notification. Lack of methodological uniformity in
      management emphasis the need for standardization including construction of
      management algorithm for ophthalmologists.

PMID- 20811279
TI  - Recommendations for visual evaluations of patients treated with vigabatrin.
AB  - PURPOSE OF REVIEW: Although vigabatrin has been used for many years in Europe,
      this antiepileptic medication was approved for use in the USA only 1 year ago
      because of concerns for irreversible peripheral visual field loss that can result
      in functional visual disability. RECENT FINDINGS: Visual function testing
      involves both subjective and objective techniques, some of which can be
      standardized across multiple centers. With these subjective and objectives issues
      as a reference, the current literature about the pathogenesis of vigabatrin
      visual toxicity is reviewed in order to develop a practical and reliable testing
      program for detecting peripheral visual field changes early in their course;
      thereby, hopefully limiting disabling visual field loss. SUMMARY: Based upon the
      existing literature as well as the currently available data about the evaluation
      of visual function, an algorithm has been developed to serve as a starting point
      for clinicians to evaluate patients treated with vigabatrin for refractory
      epilepsy.

PMID- 20811281
TI  - Obstructive sleep apnea and ocular disorders.
AB  - PURPOSE OF REVIEW: Obstructive sleep apnea is a diagnosis that ophthalmologists
      can screen for when a patient presents with certain risk factors. Recent
      literature provides strong data for associations between sleep apnea and ocular
      disorders. RECENT FINDINGS: A potentially serious disorder, sleep apnea can lead
      to many systemic and ocular complications. Recent findings provide data on the
      prevalence of sleep apnea with various disorders. Adequate treatment of sleep
      apnea has also shown to reverse both systemic and eye-related complications.
      SUMMARY: Early diagnosis and management of sleep apnea is critical for reducing
      the risk of devastating systemic complications and preserving ocular and visual
      function. Further longitudinal data are needed to see the effectivity of long
      term management of sleep apnea and its impact on reversing associated
      complications.

PMID- 20811282
TI  - Ophthalmologic features of the common spinocerebellar ataxias.
AB  - PURPOSE OF REVIEW: The spinocerebellar ataxias (SCAs) are a phenotypically and
      genetically diverse group of autosomal dominant disorders that cause pathological
      degeneration in the cerebellum, brainstem, and retina, resulting in a wide
      variety of ophthalmologic signs and symptoms. RECENT FINDINGS: The genetic
      discrimination of the SCAs has advanced dramatically over the past decade. The
      most common genetic (mutational) mechanism for the SCAs is an abnormal expansion
      to a stretch of glutamine amino acid residues (polyglutamine tract) encoded by
      any of several SCA-causing genes. Knowledge regarding the pathophysiology of
      polyglutamine-expansion-induced protein dysfunction is an area of intense
      investigation. SUMMARY: The ophthalmologist may be the first to encounter a
      patient with SCA, and a review of the most common genetic subtypes of this
      disorder is helpful in diagnosis and management.

PMID- 20811283
TI  - Diagnosis and management of giant cell arteritis: a review.
AB  - PURPOSE OF REVIEW: This article aims to provide a review of giant cell arteritis
      (GCA) clinical features, differential diagnosis, treatment options, and recent
      literature. RECENT FINDINGS: GCA, first described by Horton et al., is a systemic
      immune-mediated vasculitis affecting medium-sized and large-sized arteries.
      Characteristic findings include headache, jaw claudication, visual loss, and
      constitutional symptoms (malaise, fever, weight loss, loss of appetite).
      Localized GCA symptoms are the end-result of vascular insufficiency and tissue
      ischemia. Temporal artery biopsy (TAB) remains the gold standard for diagnosis.
      Additional diagnostic tests include blood tests (erythrocyte sedimentation rate,
      ESR; C-reactive protein, CRP; platelets) and imaging modalities (ultrasound of
      the arteries; fluorescein angiography, FA; MRI; and positron emission tomography,
      PET). The mainstay of management includes high-dose corticosteroids, and
      additional cytotoxic drugs, antitumor necrosis factor monoclonal antibody, and
      antiplatelet aggregation therapy may be used. The goal of treatment is to prevent
      ischemic damage and halt progression of visual loss in the affected eye and
      prevent involvement of the fellow eye. SUMMARY: Further research is warranted
      concerning the immunogenetics of GCA. Further treatment trials are also needed to
      develop more specific and sensitive diagnostic tests and new corticosteroid
      sparing treatment modalities.

PMID- 20811284
TI  - Occupational exposure to ethylene oxide and risk of lymphoma.
AB  - BACKGROUND: Ethylene oxide, a high-volume commodity, is an established human
      carcinogen, although the relevant epidemiologic evidence is limited. METHODS: We
      explored the association between occupational exposure to ethylene oxide and risk
      of lymphoma in a case-control study, including 2347 lymphoma cases first
      diagnosed in 1998-2004 and 2463 controls, from 6 European countries. The
      diagnosis of lymphoma was based on the 2001 World Health Organization
      Classification of lymphoma. Occupational exposure to ethylene oxide was
      retrospectively assessed by industrial hygienists and occupational physicians
      based on detailed self-reported information. We modeled risk of lymphoma with
      unconditional logistic regression analysis as a function of various exposure
      measures, adjusting for age, sex, and participating center. RESULTS: Thirty-one
      cases and 27 controls (1.2% of the total study population) were defined as ever
      having been exposed to ethylene oxide (odds ratio = 1.3 [95% confidence interval
      [CI] = 0.7-2.1]). Lymphoma risk showed a 4.3-fold increase associated with medium
      high frequency of exposure to ethylene oxide (95% CI = 1.4-13). Among major
      subtypes, chronic lymphocytic leukemia was consistently associated with ethylene
      oxide exposure, related in a dose-response manner to probability, frequency, and
      duration of exposure, as well as to cumulative exposure and (less definitively)
      with exposure intensity. CONCLUSIONS: Our results add to the evidence that
      ethylene oxide is a human carcinogen.

PMID- 20811285
TI  - Witness of intimate partner violence in childhood and perpetration of intimate
      partner violence in adulthood.
AB  - BACKGROUND: At least half a million women are victims of intimate partner
      violence in the United States annually, resulting in substantial harm. However,
      the etiology of violence to intimate partners is not well understood. Witnessing
      such violence in childhood has been proposed as a principal cause of adulthood
      perpetration, yet it remains unknown whether the association between witnessing
      intimate partner violence and adulthood perpetration is causal. METHOD: We
      conducted a propensity-score analysis of intimate partner violence perpetration
      to determine whether childhood witnessing is associated with perpetration in
      adulthood, independent of a wide range of potential confounding variables, and
      therefore might be a causal factor. We used data from 14,564 U.S. men ages 20 and
      older from the 2004-2005 wave of the National Epidemiologic Survey on Alcohol and
      Related Conditions. RESULTS: Nearly 4% of men reported violent behavior toward an
      intimate partner in the past year. In unadjusted models, we found a strong
      association between childhood witnessing of intimate partner violence and
      adulthood perpetration (for witnessing any intimate partner violence, risk ratio
      [RR] = 2.6 [95% confidence interval = 2.1-3.2]; for witnessing frequent or
      serious violence, 3.0 [2.3-3.9]). In propensity-score models, the association was
      substantially attenuated (for witnessing any intimate partner violence, adjusted
      RR = 1.6 [1.2-2.0]; for witnessing frequent or serious violence, 1.6 [1.2-2.3]).
      CONCLUSIONS: Men who witness intimate partner violence in childhood are more
      likely to commit such acts in adulthood, compared with men who are otherwise
      similar with respect to a large range of potential confounders. Etiological
      models of intimate partner violence perpetration should consider a constellation
      of childhood factors.

PMID- 20811286
TI  - Prenatal exposure to fine particulate matter and birth weight: variations by
      particulate constituents and sources.
AB  - BACKGROUND: Exposure to fine particles (PM2.5) during pregnancy has been linked
      to lower birth weight; however, the chemical composition of PM2.5 varies widely.
      The health effects of PM2.5 constituents are unknown. METHODS: We investigated
      whether PM2.5 mass, constituents, and sources are associated with birth weight
      for term births. PM2.5 filters collected in 3 Connecticut counties and 1
      Massachusetts county from August 2000 through February 2004 were analyzed for
      more than 50 elements. Source apportionment was used to estimate daily
      contributions of PM2.5 sources, including traffic, road dust/crustal, oil
      combustion, salt, and regional (sulfur) sources. Gestational and trimester
      exposure to PM2.5 mass, constituents, and source contributions were examined in
      relation to birth weight and risk of small-at-term birth (term birth <2500 g) for
      76,788 infants. RESULTS: Road dust and related constituents such as silicon and
      aluminum were associated with lower birth weight, as were the motor-vehicle
      related species such as elemental carbon and zinc, and the oil-combustion
      associated elements vanadium and nickel. An interquartile range increase in
      exposure was associated with low birthweight for zinc (12% increase in risk),
      elemental carbon (13%), silicon (10%), aluminum (11%), vanadium (8%), and nickel
      (11%). Analysis by trimester showed effects of third-trimester exposure to
      elemental carbon, nickel, vanadium, and oil-combustion PM2.5. CONCLUSIONS:
      Exposures of pregnant women to higher levels of certain PM2.5 chemical
      constituents originating from specific sources are associated with lower birth
      weight.

PMID- 20811287
TI  - Associations of primary and secondary organic aerosols with airway and systemic
      inflammation in an elderly panel cohort.
AB  - BACKGROUND: Exposure-response information about particulate air-pollution
      constituents is needed to protect sensitive populations. Particulate matter <2.5
      mm (PM2.5) components may induce oxidative stress through reactive-oxygen-species
      generation, including primary organics from combustion sources and secondary
      organics from photochemically oxidized volatile organic compounds. We evaluated
      differences in airway versus systemic inflammatory responses to primary versus
      secondary organic particle components, particle size fractions, and the potential
      of particles to induce cellular production of reactive oxygen species. METHODS: A
      total of 60 elderly subjects contributed up to 12 weekly measurements of
      fractional exhaled nitric oxide (NO; airway inflammation biomarker), and plasma
      interleukin-6 (IL-6; systemic inflammation biomarker). PM2.5 mass fractions were
      PM0.25 (<0.25 MUm) and PM0.25-2.5 (0.25-2.5 MUm). Primary organic markers
      included PM2.5 primary organic carbon, and PM0.25 polycyclic aromatic
      hydrocarbons and hopanes. Secondary organic markers included PM2.5 secondary
      organic carbon, and PM0.25 water soluble organic carbon and n-alkanoic acids.
      Gaseous pollutants included carbon monoxide (CO) and nitrogen oxides (NOx;
      combustion emissions markers), and ozone (O3; photochemistry marker). To assess
      PM oxidative potential, we exposed rat alveolar macrophages in vitro to aqueous
      extracts of PM0.25 filters and measured reactive-oxygen-species production.
      Biomarker associations with exposures were evaluated with mixed-effects models.
      RESULTS: Secondary organic markers, PM0.25-2.5, and O3 were positively associated
      with exhaled NO. Primary organic markers, PM0.25, CO, and NOx were positively
      associated with IL-6. Reactive oxygen species were associated with both outcomes.
      CONCLUSIONS: Particle effects on airway versus systemic inflammation differ by
      composition, but overall particle potential to induce generation of cellular
      reactive oxygen species is related to both outcomes.

PMID- 20811288
TI  - Exogenous carbon monoxide does not affect cell membrane energy availability
      assessed by sarcolemmal calcium fluxes during myocardial ischaemia-reperfusion in
      the pig.
AB  - Carbon monoxide is thought to be cytoprotective and may hold therapeutic promise
      for mitigating ischaemic injury. The purpose of this study was to test low-dose
      carbon monoxide for protective effects in a porcine model of acute myocardial
      ischaemia and reperfusion. In acute open-thorax experiments in anaesthetised
      pigs, pretreatment with low-dose carbon monoxide (5% increase in
      carboxyhaemoglobin) was conducted for 120 min before localised ischaemia (45 min)
      and reperfusion (60 min) was performed using a coronary snare. Metabolic and
      injury markers were collected by microdialysis sampling in the ventricular wall.
      Recovery of radio-marked calcium delivered locally by microperfusate was measured
      to assess carbon monoxide treatment effects during ischaemia/reperfusion on the
      intracellular calcium pool. Coronary occlusion and ischaemia/reperfusion were
      analysed for 16 animals (eight in each group). Changes in glucose, lactate and
      pyruvate from the ischaemic area were observed during ischaemia and reperfusion
      interventions, though there was no difference between carbon monoxide-treated and
      control groups during ischaemia or reperfusion. Similar results were observed for
      glycerol and microdialysate 45Ca(2+) recovery. These findings show that a
      relatively low and clinically relevant dose of carbon monoxide did not seem to
      provide acute protection as indicated by metabolic, energy-related and injury
      markers in a porcine myocardial ischaemia/reperfusion experimental model. We
      conclude that protective effects of carbon monoxide related to
      ischaemia/reperfusion either require higher doses of carbon monoxide or occur
      later after reperfusion than the immediate time frame studied here. More study is
      needed to characterise the mechanism and time frame of carbon monoxide-related
      cytoprotection.

PMID- 20811289
TI  - p24 antigen rapid test for diagnosis of acute pediatric HIV infection.
AB  - Currently, the majority of HIV-infected infants are found within limited-resource
      settings, where inadequate screening for HIV due to the lack of access to simple
      and affordable point-of-care tests impedes implementation of antiretroviral
      therapy. Here we report development of a low-cost dipstick p24 antigen assay
      using a visual readout format that can facilitate the diagnosis of HIV for
      infants in resource-poor conditions. A heat shock methodology was developed to
      optimize disruption of immune complexes present in the plasma of infected
      infants. The analytical sensitivity of the assay using recombinant p24 antigen is
      50 pg/mL (2 pM) with whole virus detection as low as 42.5k RNA copies per
      milliliter plasma. In a blinded study comprising 51 archived infant samples from
      the Women and Infants Transmission Study, our assay demonstrated an overall
      sensitivity and specificity of 90% and 100%, respectively. In field evaluations
      of 389 fresh samples from South African infants, a sensitivity of 95% and
      specificity of 99% was achieved. The assay is simple to perform, requires minimal
      plasma volume (25 MUL), and yields a result in less than 40 minutes making it
      ideal for implementation in resource-limited settings.

PMID- 20811291
TI  - Exercise training can attenuate preeclampsia-like features in an animal model.
AB  - OBJECTIVE: Exercise training benefits have been widely investigated and used as
      alternative treatment for different pathological conditions. Since preeclampsia
      is a severe pregnancy-associated disease for which no treatment is available, our
      aim was to investigate the protective role of exercise training on pregnancy
      outcome using a mouse model of the disease. METHODS: We used transgenic female
      mice overexpressing human angiotensinogen, which develop preeclampsia when mated
      with human renin-overexpressing males. Females were placed in exercise cages 4
      weeks prior to mating, and remained in these throughout gestation. Blood pressure
      was measured by telemetry, and proteinuria was quantified by ELISA. Placentas
      were assessed by histology and immunohistochemistry, whereas vascular endothelial
      growth factor was measured by real-time PCR and immunoblot. Endothelial function
      was assessed in isolated mesenteric arteries. RESULTS: Conversely to sedentary
      transgenic females (131.20 +/- 4.08 mmHg), trained dam's mean arterial pressure
      was no longer different from normal mice at the end of gestation (117.5 +/- 10.6
      vs. 112.3 +/- 5.5 mmHg). Proteinuria observed in transgenic dams (3.364 +/- 1.62
      MUg/mg) was absent in trained mice (0.894 +/- 0.43 MUg/mg). Placental disease and
      cardiac hypertrophy were also normalized, whereas vascular reactivity was
      significantly ameliorated. Furthermore, placental vascular endothelial growth
      factor was normalized in trained transgenic mice. CONCLUSIONS: To our knowledge,
      we are the first to clearly demonstrate that exercise training both before and
      during gestation can reduce preeclampsia features in a mouse model. Consequently,
      women at risk for this disease could benefit from exercise training to protect
      themselves and their future fetuses.

PMID- 20811293
TI  - Predictors of clinical outcome after stent placement in atherosclerotic renal
      artery stenosis: a systematic review and meta-analysis of prospective studies.
AB  - OBJECTIVE: To determine clinical predictors for blood pressure and/or renal
      function improvement after renal artery stent placement in atherosclerotic renal
      artery stenosis (ARAS). METHODS: We searched PubMed, EMBASE and Cochrane
      databases for prospective studies investigating clinical predictive variables for
      renal function and/or blood pressure improvement after stent placement in ARAS.
      Eleven studies (1552 participants) were selected for our systematic review and
      meta-analysis. Meta-regression analysis was performed to investigate
      heterogeneity and to determine independent predictors for the outcome variables.
      Bias was evaluated by use of the Cochrane risk of bias tool. RESULTS:
      Multivariate meta-regression analysis showed no predictors for renal function
      improvement. High baseline diastolic blood pressure (DBP) and pulse pressure were
      significantly associated with the decrease in blood pressure after intervention.
      These results were consistent with the predictors reported by the individual
      studies. Meta-analysis showed a nonsignificant decline in serum creatinine of 4.7
      MUmol/l [95% confidence interval (Cl) -13.8 to 4.5]. Overall, systolic blood
      pressure (SBP) fell by 19.2 mmHg (95% Cl -22.7 to -15.7) and DBP decreased 8.9
      mmHg (95% Cl -10.8 to -7.0). Risk of bias was present in the majority of the
      studies. CONCLUSIONS: The present review did not find a clinical characteristic
      that reliably predicts renal function outcome. High baseline pulse pressure
      predicted a smaller decrease in SBP after intervention and the best clinical
      predictor for a larger DBP reduction was a high pretreatment DBP.

PMID- 20811294
TI  - Evaluating 24-h antihypertensive efficacy by the smoothness index: a meta
      analysis of an ambulatory blood pressure monitoring database.
AB  - OBJECTIVE: The aim of this meta-analysis was to compare the 24-h antihypertensive
      efficacy of different treatments using the smoothness index. METHODS: Data were
      taken from the telmisartan ambulatory blood pressure monitoring (ABPM) clinical
      programme. Eleven clinical trials that randomized mild-to-moderate hypertensive
      patients to treatment with telmisartan 40/80 mg, losartan 50 mg, valsartan 80/160
      mg, ramipril 10 mg, amlodipine 5 mg monotherapy, or with an angiotensin receptor
      blocker (ARB) and hydrochlorothiazide (HCTZ) 12.5/25 mg, were included. Treatment
      duration ranged from 4 to 14 weeks. The smoothness index was calculated according
      to the published formula. RESULTS: Altogether, 5188 patients were included (65%
      men; 52% were using telmisartan as monotherapy or in combination with HCTZ).
      Telmisartan 80 mg had a higher smoothness index than losartan, valsartan or
      ramipril (P < 0.05), and was comparable with amlodipine. All combination
      therapies had a higher smoothness index than monotherapy; the largest value was
      observed with telmisartan 80 mg and HCTZ 12.5 mg. Overall, the smoothness index
      was lower in men, older patients, black patients, smokers and in those with lower
      baseline blood pressure (P < 0.05). CONCLUSION: The smoothness index was affected
      by age, race, sex, behavioural and haemodynamic factors. It was also able to
      differentiate the 24-h blood pressure effects of antihypertensive drugs, with
      telmisartan and amlodipine achieving the highest values, possibly because of
      their long plasma half-lives. All combination therapies had a higher smoothness
      index than monotherapy. An understanding of the relative effects of different
      antihypertensives on the smoothness index may help to differentiate their
      effectiveness in reducing blood pressure-related cardiovascular risk.

PMID- 20811290
TI  - Dialysis and renal transplantation in HIV-infected patients: a European survey.
AB  - OBJECTIVES: To determine prevalence and characteristics of end-stage renal
      diseases (ESRD) [dialysis and renal transplantation (RT)] among European HIV
      infected patients. METHODS: Cross-sectional multicenter survey of EuroSIDA
      clinics during 2008. RESULTS: Prevalence of ESRD was 0.5%. Of 122 patients with
      ESRD 96 were on dialysis and 26 had received a RT. Median age was 47 years, 73%
      were males and 43% were black. Median duration of HIV infection was 11 years.
      Thirty-three percent had prior AIDS; 91% were receiving antiretrovirals; and 88%
      had undetectable viral load. Median CD4(+)T-cell count was 341 cells per cubic
      millimetre; 20.5% had hepatitis C coinfection. Most frequent causes of ESRD were
      HIV-associated nephropathy (46%) and other glomerulonephritis (28%). Hemodialysis
      (93%) was the most common dialysis modality; 34% of patients were on the RT
      waiting list. A poor HIV control was the reason for exclusion from RT waiting
      list in 22.4% of cases. All the RT recipients were all alive at the time of the
      survey. Acute rejection was reported in 8 patients (30%). Functioning graft was
      present in 21 (80%). CONCLUSIONS: This is the first multinational cross-sectional
      study of ESRD among European HIV population. Low prevalence of ESRD was found.
      Two-thirds of patients were excluded from RT for non-HIV/AIDS-related
      pathologies. Most patients had a functioning graft despite a high acute rejection
      rate.

PMID- 20811292
TI  - Genetic variants in the renin-angiotensin system and blood pressure reactions to
      the cold pressor test.
AB  - OBJECTIVES: The purpose of this study was to examine the association between
      genetic variants in the renin-angiotensin system and blood pressure (BP)
      responses to the cold pressor test (CPT). METHODS: The CPT was conducted among
      1998 Han Chinese participants. BP measurements were obtained before and after the
      CPT using a standard sphygmomanometer according to a standard protocol. The
      association between SNP genotypes and BP responses to the CPT was assessed using
      a mixed linear model. RESULTS: Of 68 SNPs genotyped in six renin-angiotensin
      system genes, two were strongly associated with DBP responses to CPT (P <= 0.001;
      false discovery rate q value < 0.05): rs2006765 and rs943580 in the
      angiotensinogen (AGT) gene. Compared to C allele carriers of rs2006765, the TT
      homozygotes had a significantly decreased DBP response to the CPT. For
      participants with the TT genotype, percentage DBP responses were 5.68% (4.25
      7.10%), compared to corresponding responses of 9.17% (8.66-9.68%) among
      participants with the CC+CT genotype. In addition, SNP rs4681443 of the
      angiotensin type 1 receptor (AGTR1) gene was significantly associated with
      percentage SBP responses to CPT (P <= 0.001; q-value <0.05). CONCLUSION: Briefly,
      our study identified variants in the AGT and AGTR1 genes that may influence BP
      responses to CPT in the Han Chinese population. These results show that genetic
      variants in the renin-angiotensin system play an important role in BP responses
      to CPT and, therefore, in predicting future hypertension.

PMID- 20811295
TI  - Overexpression of coupling factor 6 causes cardiac dysfunction under high-salt
      diet in mice.
AB  - OBJECTIVE: Reactive oxygen species are involved in the pathogenesis of congestive
      heart failure. We recently showed that coupling factor 6, a component of
      adenosine trisphosphate (ATP) synthase, induces hypertension by intracellular
      acidosis, which is related to reactive oxygen species generation. We investigated
      the effect of high-salt diet on the cardiac performance and reactive oxygen
      species generation in coupling factor 6-overexpressing transgenic mice. METHODS
      AND RESULTS: Baseline echocardiographic findings, reactive oxygen species
      generation, protein expression of sarcoplasmic/endoplasmic reticulum of Ca-ATPase
      2 and phospholamban, and ATP content in the heart were similar between 7-week-old
      transgenic and wild-type mice. When the mice were fed with 8% salt diet for 20-24
      weeks, fractional shortening of the left ventricle was decreased in transgenic
      mice compared with wild-type mice and was recovered by intraperitoneal
      administration of anticoupling factor 6 antibody. Nicotinamide adenine
      dinucleotide phosphate oxidase activity in the heart was increased in transgenic
      mice after the high-salt diet concomitantly with c-Src activation. The level of 8
      iso-prostaglandin F2alpha was increased in transgenic heart compared with wild
      type heart. The protein expression of sarcoplasmic/endoplasmic reticulum of Ca
      ATPase 2 was decreased and that of phospholamban was increased in transgenic
      heart. In cDNA microarray analysis, the genes related to ATP synthesis and
      glycolysis were decreased in transgenic heart, concomitantly with the decrease in
      ATP content and the increase in beta-myosin heavy chain. CONCLUSION: These
      suggest that coupling factor 6 induces the development of systolic dysfunction
      and upregulation of nicotinamide adenine dinucleotide phosphate oxidase in the
      heart under the high-salt diet.

PMID- 20811296
TI  - Urinary proteomic diagnosis of coronary artery disease: identification and
      clinical validation in 623 individuals.
AB  - OBJECTIVES: We studied the urinary proteome in a total of 623 individuals with
      and without coronary artery disease (CAD) in order to characterize multiple
      biomarkers that enable prediction of the presence of CAD. METHODS: Urine samples
      were analyzed by capillary electrophoresis coupled online to micro time-of-flight
      mass spectrometry. RESULTS: We defined a pattern of 238 CAD-specific polypeptides
      from comparison of 586 spot urine samples from 408 individuals. This pattern
      identified patients with CAD in a blinded cohort of 138 urine samples (71
      patients with CAD and 67 healthy individuals) with high sensitivity and
      specificity (area under the receiver operator characteristic curve 87%, 95%
      confidence interval 81-92) and was superior to previously developed 15-marker
      (area under the receiver operator characteristic curve 68%, P < 0.0001) and 17
      marker panels (area under the receiver operator characteristic curve 77%, P <
      0.0001). The sequences of the discriminatory polypeptides include fragments of
      alpha-1-antitrypsin, collagen types 1 and 3, granin-like neuroendocrine peptide
      precursor, membrane-associated progesterone receptor component 1,
      sodium/potassium-transporting ATPase gamma chain and fibrinogen-alpha chain.
      Several biomarkers changed significantly toward the healthy signature following 2
      year treatment with irbesartan, whereas short-term treatment with irbesartan did
      not significantly affect the polypeptide pattern. CONCLUSION: Urinary proteomics
      identifies CAD with high confidence and might also be useful for monitoring the
      effects of therapeutic interventions.

PMID- 20811297
TI  - Orthopedic complications related to growth hormone therapy in a pediatric
      population.
AB  - Since the introduction of recombinant growth hormone, its use has diversified and
      multiplied. Growth hormone is now the recommended therapy for a growing
      indication to all forms of short stature because of its direct and indirect role
      on bone growth. Hereby, we discuss the orthopedic complications associated with
      growth hormone treatment in pediatric patients. These complications include
      carpal tunnel syndrome, Legg-Calve-Perthes' disease, scoliosis, and slipped
      capital femoral epiphysis. Their incidence rates recorded in several growth
      hormone therapy-related pharmacovigilance studies will be summarized in this
      study with focused discussion on their occurrence in the pediatric and adolescent
      age groups. The pathogenesis of these complications is also reviewed.

PMID- 20811298
TI  - Heart as a source of stroke: imaging evaluation with computed tomography.
AB  - Stroke from cardiac sources is a major cause of cerebral infarctions and
      ischemia. Cardiac sources of stroke include intracardiac thrombus, right-to-left
      shunts, tumors, and slow-flow states resulting from hemodynamic compromise.
      Computed tomography angiography of the neck is currently used for the evaluation
      of a suspected stroke. The availability of longer multidetector computed
      tomography detector arrays and prospective echocardiography triggering techniques
      could permit evaluation of the chest, head, and neck during the same examination,
      streamlining patient evaluation and management.

PMID- 20811299
TI  - Effects of myo-inositol supplementation in postmenopausal women with metabolic
      syndrome: a perspective, randomized, placebo-controlled study.
AB  - OBJECTIVE: The aim of this study was to evaluate whether myo-inositol, an insulin
      sensitizing substance, may improve some features of metabolic syndrome in
      postmenopausal women. METHODS: Eighty postmenopausal women affected by the
      metabolic syndrome were enrolled prospectively in the study and treated with diet
      plus supplementation of myo-inositol (2 g BID plus diet: intervention group) or
      with diet plus placebo (control group) for 6 months. They were evaluated at
      baseline and after 6 months for insulin resistance (homeostasis model assessment
      ratio [HOMA] insulin resistance), lipid profile, and blood pressure. RESULTS: Myo
      inositol plus diet improved systolic and diastolic blood pressure, HOMA index,
      cholesterol, and triglyceride serum levels with highly significant differences,
      compared with the groups treated only with diet and placebo. In the group treated
      with myo-inositol, a decrease in diastolic blood pressure (-11%), HOMA index (
      75%), and serum triglycerides (-20%) and an improvement in high-density
      lipoprotein cholesterol (22%) were shown. CONCLUSIONS: Supplementation with myo
      inositol may be considered a reliable option in the treatment of metabolic
      syndrome in postmenopausal women.

PMID- 20811300
TI  - Rat hippocampus-prefrontal multiple units and synaptic efficacy in vivo.
AB  - We recorded multiple unit activities of the CA1 region of the intermediate
      hippocampus and prelimbic area of the prefrontal cortex, and evoked responses in
      the prefrontal cortex by hippocampal stimulation in urethane-anesthetized rats.
      The multiple unit activities between these regions showed significant peaks of
      cross-correlograms, which indicated that firing initiated mainly from either the
      hippocampus (type HP) or the prefrontal cortex (type PH). In type HP, the slopes
      of evoked responses showed a significant inverse correlation with peak heights of
      cross-correlograms and number of bursts of multiple unit activities. These
      results suggest that multiple unit activity-based cross-correlograms (a
      measurement to test functional connectivity) are influenced by both evoked
      response (synaptic connectivity) and effects of local circuits.

PMID- 20811301
TI  - Differential modulation of valence and arousal in high-alexithymic and low
      alexithymic individuals.
AB  - High-alexithymic individuals are characterized by an impaired ability to identify
      and communicate emotions whereas low-alexithymic individuals have a wide-ranging
      ability to deal with emotions. This study examined the hypothesis that valence
      and arousal modifications of emotional stimuli differentially modulate cortical
      regions in high-alexithymic and low-alexithymic individuals. To this end, 28 high
      alexithymic and 25 low-alexithymic individuals were investigated with event
      related fMRI using visual emotional stimuli. We found differential neural
      activations in the dorsal anterior cingulate, the insula and the amygdala. We
      suggest that these differences may account for the impaired ability of high
      alexithymic individuals to appropriately handle emotional stimuli.

PMID- 20811304
TI  - Reply re: "Levator excursion and its relationship to lid lag in thyroid eye
      disease".

PMID- 20811305
TI  - Re: "Outcomes in silicone rod frontalis suspension surgery for high-risk
      noncongenital blepharoptosis".

PMID- 20811306
TI  - Re: "Muscle prolapse after harvesting autogenous fascia lata used for frontalis
      suspension in children".

PMID- 20811307
TI  - Hyperbaric oxygen therapy as further adjunctive therapy in the treatment of
      periorbital necrotizing fasciitis caused by group A Streptococcus.

PMID- 20811308
TI  - Re: "Inferolateral migration of hydrogel orbital implants in microphthalmia".

PMID- 20811310
TI  - Instilling ocular ointments without blurred vision.

PMID- 20811311
TI  - Improving hygiene in home deliveries in rural Ghana: how to build on current
      attitudes and practices.
AB  - INTRODUCTION: Clean delivery of newborns is a key intervention for reducing
      infection-related neonatal mortality. Understanding local practices and beliefs
      is important for designing appropriate interventions. There are few data from
      Africa. This study explored delivery practices in Ghana to identify behaviors for
      intervention and to determine behavioral influencers. METHODS: Data on the
      prevalence of clean delivery behaviors, collected through a demographic
      surveillance system, were analyzed for 2631 women who delivered at home within a
      1-year period. Qualitative data on delivery practices were collected through
      birth narratives, in-depth interviews, and focus groups with recently
      delivered/pregnant women, traditional birth attendants, grandmothers, and
      husbands. RESULTS: Most women delivered on a covered surface (79%), had birth
      attendants who washed their hands (79%), cut the cord with a new blade (98%), and
      tied it with a new thread (90%). Eight percent of families practiced dry cord
      care. Families understood the importance of a clean delivery surface and many
      birth attendants knew the importance of hand-washing. Delivering on an uncovered
      surface was linked to impromptu deliveries and a belief that a swept floor is
      clean. Not washing hands was linked to rushing to help the woman, not being
      provided with soap, forgetfulness, and a belief among some that the babies are
      born dirty. The frequent application of products to the cord was nearly universal
      and respondents believed that applying nothing to the cord would have serious
      negative consequences. CONCLUSIONS: Delivery surfaces, hand-washing, and cord
      cutting and tying appear appropriate for the majority of women. Changing cord
      care practices is likely to be difficult unless replacement products are
      provided.

PMID- 20811312
TI  - A report of three cases and review of intrauterine herpes simplex virus
      infection.
AB  - BACKGROUND: intrauterine herpes simplex virus (HSV) infection often is omitted
      from descriptions of neonatal HSV disease. Previous characterizations of
      intrauterine HSV infection limit manifestations to the triad of cutaneous,
      central nervous system (CNS), and ophthalmologic findings. We report 3 cases of
      intrauterine HSV infection and provide a contemporary literature review of this
      disease. METHODS: cases published between 1963 and January 2009 were identified.
      Selected cases fit the clinical description of intrauterine HSV infection, had
      manifestations present at birth, and had virologic confirmation of infection.
      RESULTS: this review yielded 64 cases, 3 of which were our own, of intrauterine
      HSV infection. Less than one-third fit the typical triad. Of the patients with
      cutaneous findings at birth, 24 (44%) had manifestations other than vesicles or
      bullae. Confirmation of HSV infection by culture of cutaneous lesions present at
      birth was delayed beyond 72 hours after birth in 15 patients and occurred at a
      median of 10 days of age. Nine of these patients had lesions at birth that were
      neither vesicles nor bullae, and 14 cases were confirmed by culture of new
      vesicles. CONCLUSIONS: more than two-thirds of reported cases do not present with
      the typical triad. Cutaneous findings are not limited to vesicles or bullae. A
      high index of suspicion and recognition of varied cutaneous manifestations is
      necessary to diagnose infants with intrauterine HSV infection.

PMID- 20811313
TI  - Severe pertussis in infants: estimated impact of first vaccine dose at 6 versus 8
      weeks in australia.
AB  - We estimated the potential benefits of advancing the first dose of pertussis
      vaccine for infants from 8 to 6 weeks of age, using Australian national disease
      databases. Infants had notification rates 3-fold greater than the general
      population and accounted for 52% of recorded hospitalizations. Infants 1 and 2
      months of age had notification rates 3.5 times (95% CI: 2.7-4.5) higher than
      infants 3 to 11 months of age. Estimation of acceleration of the vaccine to 6
      weeks of age reduced average notifications, hospitalizations, and hospital bed
      days by 8%, 9%, and 12%, respectively, with larger reductions in an epidemic
      year.

PMID- 20811314
TI  - Neurologic manifestations of pediatric novel h1n1 influenza infection.
AB  - Reported neurologic manifestations of novel H1N1 influenza have included seizure,
      meningoencephalitis, and acute necrotizing encephalopathy. We describe the first
      series of pediatric patients presenting during the second wave of the US novel
      H1N1 pandemic, with protracted seizures, severe encephalopathy/encephalitis, and
      acute disseminated encephalomyelitis. In addition to prominent radiographic
      abnormalities, we provide the first observation and description of associated
      cerebrospinal fluid abnormalities.

PMID- 20811315
TI  - Severe coinfections of dengue and pandemic influenza A H1N1 viruses.
AB  - Here we report on 4 hospitalized patients with dengue-influenza virus
      coinfections. All patients were RT-PCR positive for dengue virus and pandemic
      influenza A H1N1. Clinical findings at presentation ranged from influenza-like
      illness to severe dengue. Clinical progression of the infections varied, but all
      developed dengue symptoms and had interstitial infiltrates. Three cases required
      intensive care management and 1 case was fatal.

PMID- 20811316
TI  - SLC19A1 pharmacogenomics summary.

PMID- 20811317
TI  - A comparison of hypoxia-inducible factor-alpha in surgically excised neovascular
      membranes of patients with diabetes compared with idiopathic epiretinal membranes
      in nondiabetic patients.
AB  - PURPOSE: The purpose of this study was to first determine whether hypoxia
      inducible factor-1alpha (HIF-1 alpha) was detectable in diabetic preretinal
      membranes and to compare the presence of HIF-1alpha in fibrovascular
      proliferative diabetic retinopathy membranes with nondiabetic, idiopathic,
      epiretinal membranes. METHODS: Twelve patients with proliferative diabetic
      retinopathy membranes requiring pars plana vitrectomy and nine nondiabetic
      patients with idiopathic epiretinal membranes requiring pars plana vitrectomy
      underwent excision of these membranes. Immunohisto-chemical staining for the
      presence of HIF-1alpha was performed on the excised membranes. The degree of
      staining for HIF-1alpha (1+, 2+, and 3+ scale) and the cellular location of
      staining were determined for each specimen. Institutional Review Board approval
      and informed consent were obtained for all patients. RESULTS: Eleven of 12 (92%)
      diabetic preretinal membranes were positive for HIF-1alpha, and most had intense
      (2+ to 3+) cytoplasmic staining with occasional focal nuclear positivity. Five of
      9 (55%) nondiabetic epiretinal membranes were positive for HIF-1alpha with
      significantly weaker cytoplasmic staining (1+ to 2+) with occasional focal
      punctuate nuclear staining. CONCLUSION: Hypoxia-inducible factor-1alpha is found
      more often and more intensely in diabetic preretinal membranes compared with
      nondiabetic idiopathic epiretinal membranes.

PMID- 20811318
TI  - Immunity to pneumococcal antigens in kidney transplant recipients.
AB  - BACKGROUND: In immunocompromized patients such as kidney transplant recipients,
      vaccination against Streptococcus pneumoniae is recommended by national
      guidelines. Streptococcus pneumoniae causes pneumonia and meningitis and is
      especially harmful after coinfection with influenza virus. The aim of this study
      was to define whether clinically stable kidney transplant recipients produce
      normal concentrations of antibodies after pneumococcal vaccination. METHODS:
      Forty-three consecutive patients were immunized with Pneumovax 23 and antibodies
      against 14 pneumococcal capsular polysaccharides (serotypes) were determined
      before and 4 weeks after vaccination. For the first time, a commercially
      available serotype-specific assay (Luminex technology) was used for antibody
      detection in transplant recipients. RESULTS: After vaccination, patients
      displayed a significant increase (P<0.0001) in total antibody concentration
      against these 14 serotypes from a median of 12.1 mg/L (range: 2.6-124.0) before
      vaccination to 51.9 mg/L (4.0-160.7) 4 weeks after vaccination. In addition, they
      showed a significant increase (P<0.0001) in the number of serotypes recognized
      from a median of 9 (0-13) to 13 (3-14). Antibody responses after vaccination were
      only slightly lower than in a published cohort of vaccinated healthy controls
      (total antibody concentration: 61.5 mg/L [patients displayed 84% antibodies of
      healthy controls]; number of serotypes recognized: 14 (3-14), P=0.003 [Borgers et
      al., Clin Immunol 2010; 134: 198-205]). Spearman analysis indicated that the
      estimated glomerular filtration rate at the time of vaccination was significantly
      (P<0.05) correlated with the increase of antibody concentrations against several
      polysaccharides. CONCLUSIONS: Kidney transplant recipients can produce almost
      normal concentrations of antibodies against pneumococcal polysaccharides, and
      better renal function may lead to higher levels of protection.

PMID- 20811319
TI  - Islet transplantation using donors after cardiac death: report of the Japan Islet
      Transplantation Registry.
AB  - BACKGROUND: This report summarizes outcomes of islet transplantation employing
      donors after cardiac death (DCD) between 2004 and 2007 as reported to the Japan
      Islet Transplantation Registry. METHOD: Sixty-five islet isolations were
      performed for 34 transplantations in 18 patients with insulin-dependent diabetes
      mellitus, including two patients who had prior kidney transplantation. All but
      one donor (64/65) was DCD at the time of harvesting. RESULTS: Factors influencing
      criteria for islet release included duration of low blood pressure of the donor,
      cold ischemic time, and usage of Kyoto solution for preservation. Multivariate
      analysis selected usage of Kyoto solution as most important. Of the 18
      recipients, 8, 4, and 6 recipients received 1, 2, and 3 islet infusions,
      respectively. Overall graft survival defined as C-peptide level more than or
      equal to 0.3 ng/mL was 76.5%, 47.1%, and 33.6% at 1, 2, and 3 years,
      respectively, whereas corresponding graft survival after multiple
      transplantations was 100%, 80.0%, and 57.1%, respectively. All recipients
      remained free of severe hypoglycemia while three achieved insulin independence
      for 14, 79, and 215 days. HbA1c levels and requirement of exogenous insulin were
      significantly improved in all patients. CONCLUSION: Islet transplantation
      employing DCD can ameliorate severe hypoglycemic episodes, significantly improve
      HbA1c levels, sustain significant levels of C-peptide, and achieve insulin
      independence after multiple transplantations. Thus, DCD can be an important
      resource for islet transplantation if used under strict releasing criteria and in
      multiple transplantations, particularly in countries where heart-beating donors
      are not readily available.

PMID- 20811320
TI  - Assessment of efficacy and safety of FK778 in comparison with standard care in
      renal transplant recipients with untreated BK nephropathy.
AB  - BACKGROUND: BK polyomavirus infection has been reported in 10% to 60% of renal
      transplant recipients with progression to BK nephropathy (BKN) occurring in 1% to
      5% of patients. Graft loss occurs in up to 60% of renal transplant recipients
      with BKN. Because BK polyomavirus infection is believed, in part, to be a
      manifestation of overimmunosuppression, the current standard of care involves the
      reduction of immunosuppressants. This strategy has been associated with clearance
      of viral load, preservation of renal function, and improvement in graft survival;
      however, this may come at a risk of rejection. A safe and effective
      immunosuppressive agent that does not predispose to viral infection is needed in
      transplantation. METHODS: In a phase 2, proof-of-concept, randomized, open-label,
      parallel-group, 6-month study in renal transplant patients, FK778 (an
      investigational immunosuppressant from the malononitrilamides class) was compared
      with the current standard of care (reduction of immunosuppression) for treatment
      of newly diagnosed or untreated BKN, which was confirmed by renal biopsy.
      RESULTS: Demographic characteristics were similar between the two groups, except
      there were numerically more females in the FK778 group than in the standard care
      group. Although the treatment with FK778 decreased BK viral load in this study,
      it was associated with a less favorable rejection profile and renal function and
      a higher incidence of serious adverse events compared with reduction of
      immunosuppression. CONCLUSIONS: Data from this study are consistent with the
      findings of previous studies that found no benefit of drug therapy in the
      treatment of BKN in kidney transplant recipients.

PMID- 20811321
TI  - Can C4d immunostaining on endomyocardial biopsies be considered a prognostic
      biomarker in heart transplant recipients?
AB  - BACKGROUND: The aim of this study was to assess the significance of positive C4d
      capillary immunostaining of endomyocardial biopsies and its correlation to
      clinical outcome in adult heart transplant recipients. METHODS: Nine hundred
      eighty-five endomyocardial biopsies from 107 heart transplant recipients were
      evaluated. Immunostaining for detection of intragraft C4d capillary deposition
      was performed on paraffin-embedded tissue using anti-human C4d polyclonal
      antibody. RESULTS: Positive staining of C4d was present in 36 patients (34%) and
      antibody-mediated rejection in eight patients (7%). The patients were subdivided
      into four groups on the basis of their C4d, circulating antidonor antibodies
      (donor-specific antibodies [DSAs]), and graft function: group 1=C4d positive, DSA
      negative, and no graft dysfunction; group 2=C4d positive, DSA positive, and no
      graft dysfunction; group 3=C4d positive, DSA positive, and signs of graft
      dysfunction, and group 0 (control)=all negative. An higher mortality risk was
      found in C4d-positive patients, when compared with negative ones (unadjusted
      hazard ratios: group 1: 18, group 2: 61, and group 3: 32-fold risk; P<0.0001).
      CONCLUSIONS: Antibody-mediated rejection is a complex and ongoing phenomenon with
      different phenotypic features. C4d positive predicts worse prognosis. C4d
      positive [corrected] and DSA can be used as early mortality predictors in
      patients without signs of graft dysfunction.

PMID- 20811322
TI  - In vivo imaging and therapeutic treatments in an orthotopic mouse model of
      ovarian cancer.
AB  - Human cancer and response to therapy is better represented in orthotopic animal
      models. This paper describes the development of an orthotopic mouse model of
      ovarian cancer, treatment of cancer via oral delivery of drugs, and monitoring of
      tumor cell behavior in response to drug treatment in real time using in vivo
      imaging system. In this orthotopic model, ovarian tumor cells expressing
      luciferase are applied topically by injecting them directly into the mouse bursa
      where each ovary is enclosed. Upon injection of D-luciferin, a substrate of
      firefly luciferase, luciferase-expressing cells generate bioluminescence signals.
      This signal is detected by the in vivo imaging system and allows for a non
      invasive means of monitoring tumor growth, distribution, and regression in
      individual animals. Drug administration via oral gavage allows for a maximum
      dosing volume of 10 mL/kg body weight to be delivered directly to the stomach and
      closely resembles delivery of drugs in clinical treatments. Therefore, techniques
      described here, development of an orthotopic mouse model of ovarian cancer, oral
      delivery of drugs, and in vivo imaging, are useful for better understanding of
      human ovarian cancer and treatment and will improve targeting this disease.

PMID- 20811323
TI  - Bacterial delivery of RNAi effectors: transkingdom RNAi.
AB  - RNA interference (RNAi) represents a high effective mechanism for specific
      inhibition of mRNA expression. Besides its potential as a powerful laboratory
      tool, the RNAi pathway appears to be promising for therapeutic utilization. For
      development of RNA interference (RNAi)-based therapies, delivery of RNAi
      mediating agents to target cells is one of the major obstacles. A novel strategy
      to overcome this hurdle is transkingdom RNAi (tkRNAi). This technology uses non
      pathogenic bacteria, e.g. Escherichia coli, to produce and deliver therapeutic
      short hairpin RNA (shRNA) into target cells to induce RNAi. A first-generation
      tkRNAi-mediating vector, TRIP, contains the bacteriophage T7 promoter for
      expression regulation of a therapeutic shRNA of interest. Furthermore, TRIP has
      the Inv locus from Yersinia pseudotuberculosis that encodes invasin, which
      permits natural noninvasive bacteria to enter beta1-integrin-positive mammalian
      cells and the HlyA gene from Listeria monocytogenes, which produces listeriolysin
      O. This enzyme allows the therapeutic shRNA to escape from entry vesicles within
      the cytoplasm of the target cell. TRIP constructs are introduced into a competent
      non-pathogenic Escherichia coli strain, which encodes T7 RNA polymerase necessary
      for the T7 promoter-driven synthesis of shRNAs. A well-characterized cancer
      associated target molecule for different RNAi strategies is ABCB1 (MDR1/P
      glycoprotein, MDR1/P-gp). This ABC-transporter acts as a drug extrusion pump and
      mediates the "classical" ABCB1-mediated multidrug resistance (MDR) phenotype of
      human cancer cells which is characterized by a specific cross resistance pattern.
      Different ABCB1-expressing MDR cancer cells were treated with anti-ABCB1 shRNA
      expression vector bearing E. coli. This procedure resulted in activation of the
      RNAi pathways within the cancer cells and a considerable down regulation of the
      ABCB1 encoding mRNA as well as the corresponding drug extrusion pump.
      Accordingly, drug accumulation was enhanced in the pristine drug-resistant cancer
      cells and the MDR phenotype was reversed. By means of this model the data provide
      the proof-of-concept that tkRNAi is suitable for modulation of cancer-associated
      factors, e.g. ABCB1, in human cancer cells.

PMID- 20811324
TI  - Simultaneous FMRI and electrophysiology in the rodent brain.
AB  - To examine the neural basis of the blood oxygenation level dependent (BOLD)
      magnetic resonance imaging (MRI) signal, we have developed a rodent model in
      which functional MRI data and in vivo intracortical recording can be performed
      simultaneously. The combination of MRI and electrical recording is technically
      challenging because the electrodes used for recording distort the MRI images and
      the MRI acquisition induces noise in the electrical recording. To minimize the
      mutual interference of the two modalities, glass microelectrodes were used rather
      than metal and a noise removal algorithm was implemented for the
      electrophysiology data. In our studies, two microelectrodes were separately
      implanted in bilateral primary somatosensory cortices (SI) of the rat and fixed
      in place. One coronal slice covering the electrode tips was selected for
      functional MRI. Electrode shafts and fixation positions were not included in the
      image slice to avoid imaging artifacts. The removed scalp was replaced with
      toothpaste to reduce susceptibility mismatch and prevent Gibbs ringing artifacts
      in the images. The artifact structure induced in the electrical recordings by the
      rapidly-switching magnetic fields during image acquisition was characterized by
      averaging all cycles of scans for each run. The noise structure during imaging
      was then subtracted from original recordings. The denoised time courses were then
      used for further analysis in combination with the fMRI data. As an example, the
      simultaneous acquisition was used to determine the relationship between
      spontaneous fMRI BOLD signals and band-limited intracortical electrical activity.
      Simultaneous fMRI and electrophysiological recording in the rodent will provide a
      platform for many exciting applications in neuroscience in addition to
      elucidating the relationship between the fMRI BOLD signal and neuronal activity.

PMID- 20811325
TI  - Novel apparatus and method for drug reinforcement.
AB  - Animal models of reinforcement have proven to be useful for understanding the
      neurobiological mechanisms underlying drug addiction. Operant drug self
      administration and conditioned place preference (CPP) procedures are expansively
      used in animal research to model various components of drug reinforcement,
      consumption, and addiction in humans. For this study, we used a novel approach to
      studying drug reinforcement in rats by combining traditional CPP and self
      administration methodologies. We assembled an apparatus using two Med Associate
      operant chambers, sensory stimuli, and a Plexiglas-constructed neutral zone.
      These modifications allowed our experiments to encompass motivational aspects of
      drug intake through self-administration and drug-free assessment of drug/cue
      conditioning strength with the CPP test. In our experiments, rats self
      administered cocaine (0.75 mg/kg/inj, i.v.) during either four (e.g., the "short
      term") or eight (e.g., the "long-term") alternating-day sessions in an operant
      environment containing distinctive sensory cues (e.g., olfactory and visual). On
      the alternate days, in the other (differently-cued) operant environment, saline
      was available for self-infusion (0.1 ml, i.v.). Twenty-four hours after the last
      self-administration/cue-pairing session, a CPP test was conducted. Consistent
      with typical CPP findings, there was a significant preference for the chamber
      associated with cocaine self-administration. In addition, in animals undergoing
      the long-term experiment, a significant positive correlation between CPP
      magnitude and the number of cocaine-reinforced lever responses. In conclusion,
      this apparatus and approach is time and cost effective, can be used to examine a
      wide array of topics pertaining to drug abuse, and provides more flexibility in
      experimental design than CPP or self-administration methods alone.

PMID- 20811326
TI  - Production of transgenic Xenopus laevis by restriction enzyme mediated
      integration and nuclear transplantation.
AB  - Stable integration of cloned gene products into the Xenopus genome is necessary
      to control the time and place of expression, to express genes at later stages of
      embryonic development, and to define how enhancers and promoters regulate gene
      expression within the embryo. The protocol demonstrated here can be used to
      efficiently produce transgenic Xenopus laevis embryos. This transgenesis approach
      involves three parts: 1. Sperm nuclei are isolated from adult X. laevis testis by
      treatment with lysolecithin, which permeabilizes the sperm plasma membrane. 2.
      Egg extract is prepared by low speed centrifugation, addition of calcium to cause
      the extract to progress to interphase of the cell cycle, and a high-speed
      centrifugation to isolate interphase cytosol. 3. Nuclear transplantation: the
      nuclei and extract are combined with the linearized plasmid DNA to be introduced
      as the transgene and a small amount of restriction enzyme. During a short
      reaction, egg extract partially decondenses the sperm chromatin and the
      restriction enzyme generates chromosomal breaks that promote recombination of the
      transgene into the genome. The treated sperm nuclei are then transplanted into
      unfertilized eggs. Integration of the transgene usually occurs prior to the first
      embryonic cleavage such that the resulting embryos are not chimeric. These
      embryos can be analyzed without any need to breed to the next generation,
      allowing for efficient and rapid generation of transgenic embryos for analyses of
      promoter and gene function. Adult X. laevis resulting from this procedure also
      propagate the transgene through the germline and can be used to generate lines of
      transgenic animals for multiple purposes.

PMID- 20811327
TI  - RhoC GTPase activation assay.
AB  - RhoC GTPase has 91% homology to RhoA GTPase. Because of its prevalence in cells,
      many reagents and techniques for RhoA GTPase have been developed. However, RhoC
      GTPase is expressed in metastatic cancer cells at relatively low levels.
      Therefore, few RhoC-specific reagents have been developed. We have adapted a Rho
      activation assay to detect RhoC GTPase. This technique utilizes a GST-Rho binding
      domain fusion protein to pull out active RhoC GTPase. In addition, we can harvest
      total protein at the beginning of the assay to determine levels of total (GTP and
      GDP bound) RhoC GTPase. This allows for the determination of active versus total
      RhoC GTPase in the cell. Several commercial versions of this procedure have been
      developed however, the commercial kits are optimized for RhoA GTPase and
      typically do not work well for RhoC GTPase. Parts of the assay have been modified
      as well as development of a RhoC-specific antibody.

PMID- 20811328
TI  - Generation of transgenic C. elegans by biolistic transformation.
AB  - The number of laboratories using the free living nematode C. elegans is rapidly
      growing. The popularity of this biological model is attributed to a rapid
      generation time and short life span, easy and inexpensive maintenance, fully
      sequenced genome, and array of RNAi resources and mutant animals. Additionally,
      analysis of the C. elegans genome revealed a great similarity between worms and
      higher vertebrates, which suggests that research in worms could be an important
      adjunct to studies performed in whole mice or cultured cells. A powerful and
      important part of worm research is the ability to use transgenic animals to study
      gene localization and function. Transgenic animals can be created either via
      microinjection of the worm germline or through the use of biolistic bombardment.
      Bombardment is a newer technique and is less familiar to a number of labs. Here
      we describe a simple protocol to generate transgenic worms by biolistic
      bombardment with gold particles using the Bio-Rad PDS-1000 system. Compared with
      DNA microinjection into hermaphrodite germline, this protocol has the advantage
      of not requiring special skills from the operator with regards to identifying
      worm anatomy or performing microinjection. Further multiple transgenic lines are
      usually obtained from a single bombardment. Also in contrast to microinjection,
      biolistic bombardment produces transgenic animals with both extrachromosomal
      arrays and integrated transgenes. The ability to obtain integrated transgenic
      lines can avoid the use of mutagenic protocols to integrate foreign DNA. In
      conclusion, biolistic bombardment can be an attractive method for the generation
      of transgenic animals, especially for investigators not interested in investing
      the time and effort needed to become skilled at microinjection.

PMID- 20811329
TI  - Experimental metastasis assay.
AB  - Metastasis is the leading cause of death in cancer patients. To understand the
      mechanism of metastasis, an experimental metastasis assay was established using
      immunodeficient mice. This article delineates the procedures involved in this
      assay, including sample preparation, intravenous injection, and culturing cells
      from lung metastases. Briefly, a pre-determined number of human cancer cells were
      prepared in vitro and directly injected into the circulation of immunodeficient
      mice through their tail veins. A small number of cells survive the turbulence in
      the circulation and grow as metastases in internal organs, such as lung. The
      injected mice are dissected after a certain period. The tissue distribution of
      metastases is determined under a dissecting microscope. The number of metastases
      in a specific tissue is counted and it directly correlates with the metastatic
      ability of the injected cancer cells. The arisen metastases are isolated and
      cultured in vitro as cell lines, which often show enhanced metastatic abilities
      than the parental line when injected again into immunodeficient mice. These
      highly metastatic derivatives become useful tools for identifying genes or
      molecular pathways that regulate metastatic progression.

PMID- 20811330
TI  - Tenofovir nephrotoxicity: acute tubular necrosis with distinctive clinical,
      pathological, and mitochondrial abnormalities.
AB  - Tenofovir, a widely prescribed antiretroviral medication for treatment of HIV-1
      infection, is infrequently associated with renal dysfunction and biopsy findings
      of acute tubular necrosis. We examined the clinical and pathological findings in
      13 cases of tenofovir nephrotoxicity (7 men and 6 women, mean age of 51.1+/-9.6
      years). Patients received tenofovir therapy for a mean of 19.6 months (range, 3
      weeks to 8 years; median 8 months). Nine patients presented with acute kidney
      injury, and four had mild renal insufficiency with subnephrotic proteinuria. Mean
      baseline serum creatinine was 1.3+/-0.3 mg/dl, reaching 5.7+/-4.0 mg/dl at the
      time of biopsy, with mean proteinuria of 1.6+/-0.3 g/day. Glycosuria was
      documented in seven patients, five of whom were normoglycemic. Renal biopsy
      revealed toxic acute tubular necrosis, with distinctive proximal tubular
      eosinophilic inclusions representing giant mitochondria visible by light
      microscopy. Electron microscopy showed mitochondrial enlargement, depletion, and
      dysmorphic changes. Clinical follow-up after tenofovir discontinuation was
      available for 11 of 13 patients (mean duration 13.6 months). Significant recovery
      of renal function occurred in all patients, including four who required transient
      hemodialysis. Our study shows that tenofovir nephrotoxicity is a largely
      reversible form of toxic acute tubular necrosis targeting proximal tubules and
      manifesting distinctive light microscopic and ultrastructural features of
      mitochondrial injury.

PMID- 20811331
TI  - Renal tubular Fas ligand mediates fratricide in cisplatin-induced acute kidney
      failure.
AB  - Cisplatin, a standard chemotherapeutic agent for many tumors, has an
      unfortunately common toxicity where almost a third of patients develop renal
      dysfunction after a single dose. Acute kidney injury caused by cisplatin depends
      on Fas-mediated apoptosis driven by Fas ligand (FasL) expressed on tubular
      epithelial and infiltrating immune cells. Since the role of FasL in T cells is
      known, we investigated whether its presence in primary kidney cells is needed for
      its toxic effect. We found that all cisplatin-treated wild-type (wt) mice died
      within 6 days; however, severe combined immunodeficiency (SCID)/beige mice (B-, T
      , and natural killer-cell-deficient) displayed a significant survival benefit,
      with only 55% mortality while exhibiting significant renal failure. Treating
      SCID/beige mice with MFL3, a FasL-blocking monoclonal antibody, completely
      restored survival after an otherwise lethal cisplatin dose, suggesting another
      source of FasL besides immune cells. Freshly isolated primary tubule segments
      from wt mice were co-incubated with thick ascending limb (TAL) segments freshly
      isolated from mice expressing the green fluorescent protein (GFP) transgene (same
      genetic background) to determine whether FasL-mediated killing of tubular cells
      is an autocrine or paracrine mechanism. Cisplatin-stimulated primary segments
      induced apoptosis in the GFP-tagged TAL cells, an effect blocked by MFL3. Thus,
      our study shows that cisplatin-induced nephropathy is mediated through FasL,
      functionally expressed on tubular cells that are capable of inducing death of
      cells of adjacent tubules.

PMID- 20811332
TI  - Modifiable risk factors associated with sudden cardiac arrest within hemodialysis
      clinics.
AB  - Sudden cardiac arrest is the most common cause of death among patients with end
      stage kidney disease (ESKD) maintained on hemodialysis. Here we sought to
      identify dialysis-related factors associated with this increased risk in a case
      control study encompassing 43,200 patients dialyzed in outpatient clinics of a
      large organization. Within this group, we compared the clinical and dialysis
      specific data of 502 patients who experienced a sudden cardiac arrest with 1632
      age- and dialysis-vintage-matched controls. There were 4.5 sudden cardiac arrest
      events per 100,000 dialysis treatments during the 3-year study period. These
      patients were significantly more likely to have been exposed to low potassium
      dialysate of less than 2 meq/l. These differences could not be explained by
      predialysis serum potassium levels. There was no evidence for a beneficial effect
      of low potassium dialysate even among those with higher predialysis serum
      potassium levels. Other factors strongly associated with sudden cardiac arrest by
      multivariable analysis included increased ultrafiltration volumes, exposure to
      low calcium dialysate, and predialysis serum creatinine levels. These
      relationships persisted after adjustment for covariates, but traditional risk
      factors such as history of coronary heart disease and congestive heart failure
      were not significantly influential. Hence, our study suggests that modifications
      of the hemodialysis prescription may improve the risk of sudden cardiac arrest in
      patients with ESKD.

PMID- 20811333
TI  - Association of soluble CD89 levels with disease progression but not
      susceptibility in IgA nephropathy.
AB  - The Fc-alpha receptor (FcalphaR/CD89) is involved in IgA complex formation and
      may affect the development of IgA nephropathy (IgAN). In this study, we tested
      the genetic variations of the CD89 gene in relation to disease susceptibility in
      IgAN and the expression of soluble CD89 (sCD89) in sera of patients with IgAN and
      in controls. There was a significant difference between the levels of sCD89-IgA
      complexes, measured by sandwich enzyme-linked immunosorbent assay (ELISA), in 177
      patients with IgAN with and without disease progression at the time of first
      diagnosis. No such difference was found in 42 patients with other renal diseases.
      The patients with IgAN without disease progression had stable but high levels of
      sCD89 over 5-15 years of follow-up in contrast to stable but low levels of sCD89
      in the disease progression group. Moreover, levels of sCD89 complexes were
      correlated with one of the five CD89 genetic variants in 212 patients with IgAN
      and 477 healthy Caucasians; the single-nucleotide polymorphism (SNP) rs11084377
      was significantly associated with a lower expression of sCD89. However, no
      association between CD89 gene polymorphisms and susceptibility to IgAN was
      detected. Thus, we found an association between the levels of sCD89-IgA complexes
      in serum and the severity of IgAN, and a possible genetic component in regulating
      the production or expression of sCD89.

PMID- 20811334
TI  - Low level of self-reported physical activity in ambulatory patients new to
      dialysis.
AB  - Physical inactivity contributes to the frailty and the decline in function that
      develops over time among patients with end-stage renal disease. We assessed
      physical activity among 1547 ambulatory patients new to dialysis in the United
      States Renal Data System Comprehensive Dialysis Study. We used a self-reporting
      Human Activity Profile that included Maximal and Adjusted Activity Scores and
      compared results to established norms by age and gender. Physical activity was
      found to be extremely low with scores for all age and gender categories below the
      5th percentile of healthy individuals and 95% of patients had scores consonant
      with low fitness. Older age, female gender, diabetes, atherosclerotic disease,
      and a low level of education were associated with lower activity scores assessed
      by univariate and multivariable linear regression analysis. Higher serum albumin,
      creatinine, and lower body mass index, but not hemoglobin levels, were associated
      with greater physical activity. By multivariable analysis, patients on
      hemodialysis using a catheter reported lower levels of physical activity compared
      to those on peritoneal dialysis, hemodialysis using an arteriovenous fistula, or
      with a graft. Lower Maximal and Adjusted Activity Scores were associated with
      poor physical function and mental health. Hence, physical activity is
      distressingly low among patients new to dialysis. Thus, strategies to enhance
      activity in these patients should be explored.

PMID- 20811336
TI  - Ups delivery to the intermembrane space of mitochondria: a novel affinity-driven
      protein import pathway.

PMID- 20811335
TI  - The bone and mineral disorder of children undergoing chronic peritoneal dialysis.
AB  - The mineral and bone disorder of chronic kidney disease remains a challenging
      complication in pediatric end-stage renal disease. Here, we assessed symptoms,
      risk factors and management of this disorder in 890 children and adolescents from
      24 countries reported to the International Pediatric Peritoneal Dialysis Network
      Registry. Signs of this disease were most common in North American patients. The
      prevalence of hyperphosphatemia increased with age from 6% in young infants to
      81% in adolescents. Serum parathyroid hormone (PTH) was outside the guideline
      targets in the majority of patients and associated with low calcium, high
      phosphorus, acidosis, dialysis vintage and female gender. Serum calcium was
      associated with dialytic calcium exposure, serum phosphorus with low residual
      renal function and pubertal status. PTH levels were highest in Latin America and
      lowest in Europe. Vitamin D and its active analogs were most frequently
      administered in Europe; calcium-free phosphate binders and cinacalcet in North
      America. Clinical and radiological symptoms markedly increased when PTH exceeded
      300 pg/ml, the risk of hypercalcemia increased with levels below 100 pg/ml, and
      time-averaged PTH concentrations above 500 pg/ml were associated with impaired
      longitudinal growth. Hence, the symptoms and management of the mineral and bone
      disorder of chronic kidney disease in children on peritoneal dialysis showed
      substantial regional variation. Our findings support a PTH target range of 100
      300 pg/ml in the pediatric age group.

PMID- 20811337
TI  - MEK signalling tunes actin treadmilling for interstitial lymphocyte migration.

PMID- 20811339
TI  - Spatial memory consolidation is associated with induction of several lysine
      acetyltransferase (histone acetyltransferase) expression levels and H2B/H4
      acetylation-dependent transcriptional events in the rat hippocampus.
AB  - Numerous genetic studies have shown that the CREB-binding protein (CBP) is an
      essential component of long-term memory formation, through its histone
      acetyltransferase (HAT) function. E1A-binding protein p300 and p300/CBP
      associated factor (PCAF) have also recently been involved in memory formation. By
      contrast, only a few studies have reported on acetylation modifications during
      memory formation, and it remains unclear as to how the system is regulated during
      this dynamic phase. We investigated acetylation-dependent events and the
      expression profiles of these HATs during a hippocampus-dependent task taxing
      spatial reference memory in the Morris water maze. We found a specific increase
      in H2B and H4 acetylation in the rat dorsal hippocampus, while spatial memory was
      being consolidated. This increase correlated with the degree of specific
      acetylated histones enrichment on some memory/plasticity-related gene promoters.
      Overall, a global increase in HAT activity was measured during this memory
      consolidation phase, together with a global increase of CBP, p300, and PCAF
      expression. Interestingly, these regulations were altered in a model of
      hippocampal denervation disrupting spatial memory consolidation, making it
      impossible for the hippocampus to recruit the CBP pathway (CBP regulation and
      acetylated-H2B-dependent transcription). CBP has long been thought to be present
      in limited concentrations in the cells. These results show, for the first time,
      that CBP, p300, and PCAF are dynamically modulated during the establishment of a
      spatial memory and are likely to contribute to the induction of a specific
      epigenetic tagging of the genome for hippocampus-dependent (spatial) memory
      consolidation. These findings suggest the use of HAT-activating molecules in new
      therapeutic strategies of pathological aging, Alzheimer's disease, and other
      neurodegenerative disorders.

PMID- 20811340
TI  - Cholinergic enhancement increases the effects of voluntary attention but does not
      affect involuntary attention.
AB  - Voluntary visual spatial attention can be allocated in a goal-oriented manner to
      locations containing behaviorally relevant information. In contrast, involuntary
      attention is automatically captured by salient events. Allocation of attention is
      known to be modulated by release of the neurotransmitter acetylcholine (ACh) in
      cerebral cortex. We used an anti-predictive spatial cueing task to assess the
      effects of pharmacological enhancement of cholinergic transmission on behavioral
      measures of voluntary and involuntary attention in healthy human participants.
      Each trial began with the presentation of a cue in a peripheral location. In 80%
      of the trials, a target then appeared in a location opposite the cue. In the
      remaining 20% of trials, the target appeared in the cue location. For trials with
      short stimulus onset asynchrony (SOA) between cue and target, involuntary capture
      of attention resulted in shorter reaction times (RTs) to targets presented at the
      cue location. For long SOA trials, allocation of voluntary attention resulted in
      the opposite pattern: RTs were shorter when the target appeared in the expected
      (opposite) location. Each subject participated in two sessions: one in which the
      cholinesterase inhibitor donepezil was administered to increase synaptic ACh
      levels and one in which placebo was administered. Donepezil selectively improved
      performance (reduced RT) for long SOA trials in which targets appeared in the
      expected location. Thus, cholinergic enhancement augments the benefits of
      voluntary attention but does not affect involuntary attention, suggesting that
      they rely on different neurochemical mechanisms.

PMID- 20811342
TI  - Gene expression: Small but dominant RNA.

PMID- 20811341
TI  - Episodic withdrawal promotes psychomotor sensitization to morphine.
AB  - The relative intermittency or continuity of drug delivery is a major determinant
      of addictive liability, and also influences the impact of drug exposure on brain
      function and behavior. Events that occur during the offset of drug action (ie,
      acute withdrawal) may have an important role in the consequences of intermittent
      drug exposure. We assessed whether recurrent episodes of acute withdrawal
      contribute to the development of psychomotor sensitization in rodents during
      daily morphine exposure. The acoustic startle reflex--a measure of anxiety
      induced by opiate withdrawal-was used to resolve and quantify discrete withdrawal
      episodes, and pharmacological interventions were used to manipulate withdrawal
      severity. Startle potentiation was observed during spontaneous withdrawal from a
      single morphine exposure, and individual differences in initial withdrawal
      severity positively predicted the subsequent development of sensitization.
      Manipulations that reduce or exacerbate withdrawal severity also produced
      parallel changes in the degree of sensitization. These results demonstrate that
      the episodic experience of withdrawal during daily drug exposure has a novel role
      in promoting the development of psychomotor sensitization--a prominent model of
      drug-induced neurobehavioral plasticity. Episodic withdrawal may have a pervasive
      role in many effects of intermittent drug exposure and contribute to the
      development of addiction.

PMID- 20811344
TI  - Regulation of inducible BALT formation and contribution to immunity and
      pathology.
AB  - Inducible bronchus-associated lymphoid tissue (iBALT) is an organized tertiary
      lymphoid structure that is not pre-programmed but develops in response to
      infection or under chronic inflammatory conditions. Emerging research has shown
      that iBALT provides a niche for T-cell priming and B-cell education to assist in
      the clearance of infectious agents, highlighting the prospect that iBALT may be
      engineered and harnessed to enhance protective immunity against respiratory
      pathogens. Although iBALT formation is associated with several canonical factors
      of secondary lymphoid organogenesis such as lymphotoxin-alpha and the homeostatic
      chemokines, CXCL13, CCL19, and CCL21, these cytokines are not mandatory for its
      formation, even though they influence its organization and function. Similarly,
      lymphoid tissue-inducer cells are not a requisite of iBALT formation. In
      contrast, dendritic cells are emerging as pivotal players required to form and
      sustain the presence of iBALT. Regulatory T cells appear to be able to attenuate
      the development of iBALT, although the underlying mechanisms remain ill-defined.
      In this review, we discuss facets unique to iBALT induction, the cellular
      subsets, and molecular cues that govern this process, and the contribution of
      this ectopic structure toward the generation of immune responses in the pulmonary
      compartment.

PMID- 20811343
TI  - Evaluating genome-scale approaches to eukaryotic DNA replication.
AB  - Mechanisms regulating where and when eukaryotic DNA replication initiates remain
      a mystery. Recently, genome-scale methods have been brought to bear on this
      problem. The identification of replication origins and their associated proteins
      in yeasts is a well-integrated investigative tool, but corresponding data sets
      from multicellular organisms are scarce. By contrast, standardized protocols for
      evaluating replication timing have generated informative data sets for most
      eukaryotic systems. Here, I summarize the genome-scale methods that are most
      frequently used to analyse replication in eukaryotes, the kinds of questions each
      method can address and the technical hurdles that must be overcome to gain a
      complete understanding of the nature of eukaryotic replication origins.

PMID- 20811345
TI  - The oral administration of bacterial extracts prevents asthma via the recruitment
      of regulatory T cells to the airways.
AB  - The prevalence of asthma has steadily increased during the last decade, probably
      as the result of changes in the environment, including reduced microbial exposure
      during infancy. Accordingly, experimental studies have shown that deliberate
      infections with live pathogens prevent the development of allergic airway
      diseases in mice. Bacterial extracts are currently used in children suffering
      from repeated upper respiratory tract infections. In the present study, we have
      investigated whether bacterial extracts, commercially available as Broncho-Vaxom
      (BV), could prevent allergic airway disease in mice. Oral treatment with BV
      suppressed airway inflammation through interleukin-10 (IL-10)-dependent and MyD88
      (myeloid differentiation primary response gene (88))-dependent mechanisms and
      induced the conversion of FoxP3 (forkhead box P3)(-) T cells into FoxP3(+)
      regulatory T cells. Furthermore, CD4(+) T cells purified from the trachea of BV
      treated mice conferred protection against airway inflammation when adoptively
      transferred into sensitized mice. Therefore, treatment with BV could possibly be
      a safe and efficient strategy to prevent the development of allergic diseases in
      children.

PMID- 20811347
TI  - The role of renin-angiotensin system blockade therapy in the prevention of atrial
      fibrillation: a meta-analysis of randomized controlled trials.
AB  - Current evidence suggests that angiotensin-converting enzyme inhibitors (ACEIs)
      and angiotensin II receptor blockers (ARBs) have emerged as novel drugs for
      preventing the development of atrial fibrillation (AF). A meta-analysis was
      performed of 26 randomized controlled clinical trials evaluating the effect of
      ACEIs or ARBs on the prevention of AF. Overall, ACEIs and ARBs revealed
      statistically significant preventive effects on AF (odds ratio (OR), 0.65; 95%
      confidence interval (CI), 0.55-0.76). The preventive effect was similar in the
      two classes of drugs (ACEI: OR, 0.68; ARB: OR, 0.69). ACEIs and ARBs showed
      greater preventive effects on recurrent AF (OR, 0.45; 95% CI, 0.31-0.65) than on
      new-onset AF (OR, 0.80; 95% CI, 0.70-0.92). Prevention was greatest in patients
      with AF who were receiving amiodarone as a basic treatment drug (OR, 0.35; 95%
      CI, 0.26-0.48). In patients with heart failure, there appeared to be a large
      effect (OR, 0.497), but the credible interval (CrI) limits were wide (95% CrI,
      0.187-1.161).

PMID- 20811346
TI  - Potential for pharmacokinetic interactions between ambrisentan and cyclosporine.
AB  - Ambrisentan (ABS), approved for the treatment of pulmonary arterial hypertension
      and administered as an oral dose once daily, is an ET(A)-selective endothelin
      receptor antagonist (ERA) and a potential substrate for cytochrome P450 (CYP)
      3A4, organic anion-transporting polypeptide (OATP), and P-glycoprotein (P-gp).
      Cyclosporin A (CsA), an inhibitor of CYP3A4, P-gp, and OATP, may be used
      concomitantly with ABS. In this open-label, parallel-treatment study, 28 healthy
      subjects received steady-state ABS (5 mg q.d.) either alone or with steady-state
      CsA (100-150 mg b.i.d.), and 24 other subjects received steady-state CsA either
      alone or with steady-state ABS. In the presence of CsA, ABS maximum plasma
      concentration (C(max)) increased 1.5-fold, and area under the plasma
      concentration-time curve (AUC)(0-tau) increased twofold. Marginal increases were
      observed for CsA C(max) (906 vs. 1,014 ng/ml) and AUC(0-tau) (3.05 vs. 3.37
      ug.h/ml) in the presence of ABS. Frequent adverse events (AEs) were headache and
      gastrointestinal disorders. The addition of ABS to steady-state CsA appeared less
      tolerable as compared with the addition of CsA to steady-state ABS. A maximum ABS
      dose of 5 mg is recommended if it is coadministered with CsA. No change in CsA
      dose is recommended if it is coadministered with ABS.

PMID- 20811348
TI  - Evaluation of the effects of AZD3480 on cardiac repolarization: a thorough QT/QTc
      study using moxifloxacin as a positive control.
AB  - In order to evaluate their potential effects on cardiac repolarization, all new
      drugs must undergo clinical electrocardiographic evaluation in a thorough QT/QTc
      (TQT) study. AZD3480, a central nervous system-selective, neuronal nicotinic
      receptor (NNR) agonist, is predominantly metabolized by cytochrome P450 2D6
      (CYP2D6). Employing an innovative design, this TQT study assessed the effects of
      supratherapeutic doses of AZD3480, relative to those of placebo, on cardiac
      repolarization in healthy male volunteers genotyped as either poor metabolizers
      (PMs) or extensive metabolizers (EMs) of CYP2D6 substrates. Supratherapeutic
      doses of AZD3480-resulting in ~10- and ~50-fold higher exposures (PMs and EMs,
      respectively) than achieved with a 20-mg dose-had no pharmacologic effect on
      cardiac repolarization relative to placebo. Likewise, no safety/tolerability
      concerns were observed after either supratherapeutic or 20-mg dosing to either
      population. No clinically relevant treatment-related changes or trends were
      observed in laboratory parameters, vital signs, or electrocardiogram (ECG). This
      study demonstrated that AZD3480 does not prolong QT/QTc interval.

PMID- 20811349
TI  - Pharmacovigilance data mining with methods based on false discovery rates: a
      comparative simulation study.
AB  - The early detection of adverse reactions caused by drugs that are already on the
      market is the prime concern of pharmacovigilance efforts; the methods in use for
      postmarketing surveillance are aimed at detecting signals pointing to potential
      safety concerns, on the basis of reports from health-care providers and from
      information available in various databases. Signal detection methods based on the
      estimation of false discovery rate (FDR) have recently been proposed. They
      address the limitation of arbitrary detection thresholds of the automatic methods
      in current use, including those last updated by the US Food and Drug
      Administration and the World Health Organization's Uppsala Monitoring Centre. We
      used two simulation procedures to compare the false-positive performances for
      three current methods: the reporting odds ratio (ROR), the information component
      (IC), the gamma Poisson shrinkage (GPS), and also for two FDR-based methods
      derived from the GPS model and Fisher's test. Large differences in FDR rates were
      associated with the signal-detection methods currently in use. These differences
      ranged from 0.01 to 12% in an analysis that was restricted to signals with at
      least three reports. The numbers of signals generated were also highly variable.
      Among fixed-size lists of signals, the FDR was lowered when the FDR-based
      approaches were used. Overall, the outcomes in both simulation studies suggest
      that improvement in effectiveness can be expected from use of the FDR-based GPS
      method.

PMID- 20811350
TI  - Gene-environment interactions in Parkinson's disease: the importance of animal
      modeling.
AB  - Parkinson's disease (PD), a late-onset neurodegenerative disorder, occurs most
      commonly in a "sporadic" (idiopathic) form, without a clearly defined genetic
      basis and only a vaguely delineated pathogenesis. Together, the various monogenic
      forms of PD (i.e., those arising from mutations in single genes) account for a
      minority of PD cases but have provided crucial insights into disease mechanisms.
      Although it is commonly believed that sporadic PD is caused by a lifetime of
      environmental exposures that are superimposed on an individual's composite
      genetic susceptibility, this hypothesis has not been tested adequately. This
      article reviews genetic and environmental factors that have been associated with
      PD and attempts to put these into a pathogenic framework. We argue that animal
      modeling will become increasingly important in attempting to elucidate gene
      environment interactions, to define pathogenic mechanisms, and to provide a
      platform for testing of targeted therapeutic interventions.

PMID- 20811351
TI  - The development of new therapeutics for Alzheimer's disease.
AB  - Existing treatments for Alzheimer's disease (AD) fail to address the underlying
      pathology of the disease; they merely provide short-lived symptomatic relief.
      Consequently, the progression of AD is unrelenting, leading to a continual
      decrease in cognitive abilities. Recent advances in understanding the genetic
      factors that predispose to AD, as well as in biomarker development, have brought
      with them the promise of earlier and more reliable diagnosis of this disease. As
      improvements continue to be made in these areas, the shortcomings of current AD
      treatments appear all the more acute because opportunities for early intervention
      are hindered by a lack of "curative" or even disease-modifying drugs. This State
      of the Art report reviews existing AD therapeutics and highlights recent progress
      made in the design and development of drugs that are aimed at disrupting AD
      disease progression by inhibition of the protein misfolding of beta-amyloid
      (Abeta) into neurotoxic oligomeric aggregates.

PMID- 20811352
TI  - Focusing on autophagy.

PMID- 20811353
TI  - Eaten alive: a history of macroautophagy.
AB  - Macroautophagy (hereafter autophagy), or 'self-eating', is a conserved cellular
      pathway that controls protein and organelle degradation, and has essential roles
      in survival, development and homeostasis. Autophagy is also integral to human
      health and is involved in physiology, development, lifespan and a wide range of
      diseases, including cancer, neurodegeneration and microbial infection. Although
      research on this topic began in the late 1950s, substantial progress in the
      molecular study of autophagy has taken place during only the past 15 years. This
      review traces the key findings that led to our current molecular understanding of
      this complex process.

PMID- 20811354
TI  - Autophagy in mammalian development and differentiation.
AB  - It has been known for many decades that autophagy, a conserved lysosomal
      degradation pathway, is highly active during differentiation and development.
      However, until the discovery of the autophagy-related (ATG) genes in the 1990s,
      the functional significance of this activity was unknown. Initially, genetic
      knockout studies of ATG genes in lower eukaryotes revealed an essential role for
      the autophagy pathway in differentiation and development. In recent years, the
      analyses of systemic and tissue-specific knockout models of ATG genes in mice has
      led to an explosion of knowledge about the functions of autophagy in mammalian
      development and differentiation. Here we review the main advances in our
      understanding of these functions.

PMID- 20811355
TI  - The origin of the autophagosomal membrane.
AB  - Macroautophagy is initiated by the formation of the phagophore (also called the
      isolation membrane). This membrane can both selectively and non-selectively
      engulf cytosolic components, grow and close around the sequestered components and
      then deliver them to a degradative organelle, the lysosome. Where this membrane
      comes from and how it grows is not well understood. Since the discovery of
      autophagy in the 1950s the source of the membrane has been investigated, debated
      and re-investigated, with the consensus view oscillating between a de novo
      assembly mechanism or formation from the membranes of the endoplasmic reticulum
      (ER) or the Golgi. In recent months, new information has emerged that both the ER
      and mitochondria may provide a membrane source, enlightening some older findings
      and revealing how complex the initiation of autophagy may be in mammalian cells.

PMID- 20811356
TI  - Selective autophagy: ubiquitin-mediated recognition and beyond.
AB  - Eukaryotic cells use autophagy and the ubiquitin-proteasome system as their major
      protein degradation pathways. Whereas the ubiquitin-proteasome system is involved
      in the rapid degradation of proteins, autophagy pathways can selectively remove
      protein aggregates and damaged or excess organelles. Proteasome-mediated
      degradation requires previous ubiquitylation of the cargo, which is then
      recognized by ubiquitin receptors directing it to 26S proteasomes. Although
      autophagy has long been viewed as a random cytoplasmic degradation system, the
      involvement of ubiquitin as a specificity factor for selective autophagy is
      rapidly emerging. Recent evidence also suggests active crosstalk between
      proteasome-mediated degradation and selective autophagy. Here, we discuss the
      molecular mechanisms that link autophagy and the proteasome system, as well as
      the emerging roles of ubiquitin and ubiquitin-binding proteins in selective
      autophagy. On the basis of the evolutionary history of autophagic ubiquitin
      receptors, we propose a common origin for metazoan ubiquitin-dependent autophagy
      and the cytoplasm-to-vacuole targeting pathway of yeast.

PMID- 20811357
TI  - Can autophagy promote longevity?
AB  - Organismal lifespan can be extended by genetic manipulation of cellular processes
      such as histone acetylation, the insulin/IGF-1 (insulin-like growth factor 1)
      pathway or the p53 system. Longevity-promoting regimens, including caloric
      restriction and inhibition of TOR with rapamycin, resveratrol or the natural
      polyamine spermidine, have been associated with autophagy (a cytoprotective self
      digestive process) and in some cases were reported to require autophagy for their
      effects. We summarize recent developments that outline these links and
      hypothesize that clearing cellular damage by autophagy is a common denominator of
      many lifespan-extending manipulations.

PMID- 20811358
TI  - Stressing the role of O-GlcNAc: linking cell survival to keratin modification.
AB  - Mounting evidence suggests that keratin post-translational modifications are
      crucial for many cellular processes. Now, keratin 18 modified by the addition of
      an O-linked N-acetylglucosamine residue is shown to be as a critical effector of
      stress-responsive Akt signalling, providing an important link between keratin
      glycosylation and cell survival.

PMID- 20811362
TI  - IBS: Do we need to exclude exocrine pancreatic insufficiency in IBS?

PMID- 20811363
TI  - Endoscopy: Risk assessment in upper gastrointestinal bleeding.

PMID- 20811364
TI  - Clinical guidelines: HFE hemochromatosis-screening, diagnosis and management.

PMID- 20811365
TI  - High-speed graphene transistors with a self-aligned nanowire gate.
AB  - Graphene has attracted considerable interest as a potential new electronic
      material. With its high carrier mobility, graphene is of particular interest for
      ultrahigh-speed radio-frequency electronics. However, conventional device
      fabrication processes cannot readily be applied to produce high-speed graphene
      transistors because they often introduce significant defects into the monolayer
      of carbon lattices and severely degrade the device performance. Here we report an
      approach to the fabrication of high-speed graphene transistors with a self
      aligned nanowire gate to prevent such degradation. A Co(2)Si-Al(2)O(3) core-shell
      nanowire is used as the gate, with the source and drain electrodes defined
      through a self-alignment process and the channel length defined by the nanowire
      diameter. The physical assembly of the nanowire gate preserves the high carrier
      mobility in graphene, and the self-alignment process ensures that the edges of
      the source, drain and gate electrodes are automatically and precisely positioned
      so that no overlapping or significant gaps exist between these electrodes, thus
      minimizing access resistance. It therefore allows for transistor performance not
      previously possible. Graphene transistors with a channel length as low as 140 nm
      have been fabricated with the highest scaled on-current (3.32 mA MUm(-1)) and
      transconductance (1.27 mS MUm(-1)) reported so far. Significantly, on-chip
      microwave measurements demonstrate that the self-aligned devices have a high
      intrinsic cut-off (transit) frequency of f(T) = 100-300 GHz, with the extrinsic
      f(T) (in the range of a few gigahertz) largely limited by parasitic pad
      capacitance. The reported intrinsic f(T) of the graphene transistors is
      comparable to that of the very best high-electron-mobility transistors with
      similar gate lengths.

PMID- 20811367
TI  - Antibody-drug conjugates for cancer: poised to deliver?

PMID- 20811366
TI  - Selectivity mechanism of the nuclear pore complex characterized by single cargo
      tracking.
AB  - The nuclear pore complex (NPC) mediates all exchange between the cytoplasm and
      the nucleus. Small molecules can passively diffuse through the NPC, whereas
      larger cargos require transport receptors to translocate. How the NPC facilitates
      the translocation of transport receptor/cargo complexes remains unclear. To
      investigate this process, we tracked single protein-functionalized quantum dot
      cargos as they moved through human NPCs. Here we show that import proceeds by
      successive substeps comprising cargo capture, filtering and translocation, and
      release into the nucleus. Most quantum dots are rejected at one of these steps
      and return to the cytoplasm, including very large cargos that abort at a size
      selective barrier. Cargo movement in the central channel is subdiffusive and
      cargos that can bind more transport receptors diffuse more freely. Without Ran
      GTPase, a critical regulator of transport directionality, cargos still explore
      the entire NPC, but have a markedly reduced probability of exit into the nucleus,
      suggesting that NPC entry and exit steps are not equivalent and that the pore is
      functionally asymmetric to importing cargos. The overall selectivity of the NPC
      seems to arise from the cumulative action of multiple reversible substeps and a
      final irreversible exit step.

PMID- 20811368
TI  - Potential remains for PPAR-targeted drugs.

PMID- 20811369
TI  - Deal watch: Infinity and Intellikine to develop oral PI3K inhibitors for
      inflammatory diseases.

PMID- 20811370
TI  - Deal watch: Metabolex and Sanofi-Aventis partner on GPCR agonists for type 2
      diabetes.

PMID- 20811371
TI  - Deal watch: Harnessing creative risk sharing.

PMID- 20811373
TI  - An audience with...Jim Connolly.

PMID- 20811374
TI  - The antibiotics market.

PMID- 20811375
TI  - Cabazitaxel.

PMID- 20811376
TI  - Multiple sclerosis: Putting a dampener on inflammation.

PMID- 20811377
TI  - Biotechnology: Skin patch flu vaccine shows promise.

PMID- 20811378
TI  - Antifungal drugs: Targeting histone acetylation.

PMID- 20811379
TI  - Target discovery: Blocking BTK in B-cell disorders.

PMID- 20811380
TI  - Cancer: Lethal cycling.

PMID- 20811381
TI  - Emerging principles in protease-based drug discovery.
AB  - Proteases have an important role in many signalling pathways, and represent
      potential drug targets for diseases ranging from cardiovascular disorders to
      cancer, as well as for combating many parasites and viruses. Although inhibitors
      of well-established protease targets such as angiotensin-converting enzyme and
      HIV protease have shown substantial therapeutic success, developing drugs for new
      protease targets has proved challenging in recent years. This in part could be
      due to issues such as the difficulty of achieving selectivity when targeting
      protease active sites. This Perspective discusses the general principles in
      protease-based drug discovery, highlighting the lessons learned and the emerging
      strategies, such as targeting allosteric sites, which could help harness the
      therapeutic potential of new protease targets.

PMID- 20811382
TI  - Averting inflammation by targeting the cytokine environment.
AB  - Cytokines are key instigators and regulators of immune responses and therefore
      hold great potential as targets for new therapeutic strategies. However, the
      selection of which cytokines to target, and in particular the identification of
      which cytokines regulate the rate-limiting steps of disease pathways, is crucial
      to the success of such strategies. Moreover, balancing the need for ablating
      pathological inflammatory responses and simultaneously maintaining the ability to
      control infectious agents is a key consideration. Recent advances in our
      understanding of cytokine networks, as well as technical progress in blocking
      cytokines in vivo, are likely to be a source for new drugs that can control
      chronic inflammatory diseases.

PMID- 20811385
TI  - Efonidipine improves renal function and decreases proteinuria in elderly
      hypertensive patients in the JATOS study.

PMID- 20811384
TI  - Development trends for human monoclonal antibody therapeutics.
AB  - Fully human monoclonal antibodies (mAbs) are a promising and rapidly growing
      category of targeted therapeutic agents. The first such agents were developed
      during the 1980s, but none achieved clinical or commercial success. Advances in
      technology to generate the molecules for study - in particular, transgenic mice
      and yeast or phage display - renewed interest in the development of human mAbs
      during the 1990s. In 2002, adalimumab became the first human mAb to be approved
      by the US Food and Drug Administration (FDA). Since then, an additional six human
      mAbs have received FDA approval: panitumumab, golimumab, canakinumab,
      ustekinumab, ofatumumab and denosumab. In addition, 3 candidates (raxibacumab,
      belimumab and ipilimumab) are currently under review by the FDA, 7 are in Phase
      III studies and 81 are in either Phase I or II studies. Here, we analyse data on
      147 human mAbs that have entered clinical study to highlight trends in their
      development and approval, which may help inform future studies of this class of
      therapeutic agents.

PMID- 20811387
TI  - Gene flow between Zhuang and Han populations in the China-Vietnam borderland.
AB  - In epidemiological studies, it is easier to glean information from isolated
      populations with simple genetic backgrounds than from populations with relatively
      complex genetic backgrounds. Regarded as an isolated population, the Minz (Hei-Yi
      Zhuang) in Napo County (in the China-Vietnam borderland) has been the subject of
      numerous recent studies. To assess the genetic isolation of this population, we
      studied Y chromosome and mitochondrial DNA from Minz and Han in Napo. Both
      populations exhibited southern Chinese genetic characteristics in both paternal
      and maternal lineages. Using NETWORK analyses, we found pronounced gene flow
      between these two populations only in maternal lineages. We also observed gene
      flow from other populations into the Minz gene pool. We thus concluded that the
      Minz is not a genetically isolated population and it is increasingly difficult to
      find isolated populations in mainland East Asia.

PMID- 20811383
TI  - The therapeutic potential of carbon monoxide.
AB  - Carbon monoxide (CO) is increasingly being accepted as a cytoprotective and
      homeostatic molecule with important signalling capabilities in physiological and
      pathophysiological situations. The endogenous production of CO occurs through the
      activity of constitutive (haem oxygenase 2) and inducible (haem oxygenase 1) haem
      oxygenases, enzymes that are responsible for the catabolism of haem. Through the
      generation of its products, which in addition to CO includes the bile pigments
      biliverdin, bilirubin and ferrous iron, the haem oxygenase 1 system also has an
      obligatory role in the regulation of the stress response and in cell adaptation
      to injury. This Review provides an overview of the physiology of CO, summarizes
      the effects of CO gas and CO-releasing molecules in preclinical animal models of
      cardiovascular disease, inflammatory disorders and organ transplantation, and
      discusses the development and therapeutic options for the exploitation of this
      simple gaseous molecule.

PMID- 20811386
TI  - Levosimendan improves cardiac function and survival in rats with angiotensin II
      induced hypertensive heart failure.
AB  - Calcium-sensitizing agents improve cardiac function in acute heart failure;
      however, their long-term effects on cardiovascular mortality are unknown. We
      tested the hypothesis that levosimendan, an inodilator that acts through calcium
      sensitization, opening of ATP-dependent potassium channels and phosphodiesterase
      III inhibition, improves cardiac function and survival in double transgenic rats
      harboring human renin and angiotensinogen genes (dTGRs), a model of angiotensin
      II (Ang II)-induced hypertensive heart failure. Levosimendan (1 mg kg(-1)) was
      administered orally to 4-week-old dTGRs and normotensive Sprague-Dawley rats for
      4 weeks. Untreated dTGRs developed severe hypertension, cardiac hypertrophy,
      heart failure with impaired diastolic relaxation, and exhibited a high mortality
      rate at the age of 8 weeks. Levosimendan did not decrease blood pressure and did
      not prevent cardiac hypertrophy. However, levosimendan improved systolic
      function, decreased cardiac atrial natriuretic peptide mRNA expression,
      ameliorated Ang II-induced cardiac damage and decreased mortality. Levosimendan
      did not correct Ang II-induced diastolic dysfunction and did not influence heart
      rate. In a separate survival study, levosimendan increased dTGR survival by 58%
      and median survival time by 27% (P=0.004). Our findings suggest that levosimendan
      ameliorates Ang II-induced hypertensive heart failure and reduces mortality. The
      results also support the notion that the effects of levosimendan in dTGRs are
      mediated by blood pressure-independent mechanisms and include improved systolic
      function and amelioration of Ang II-induced coronary and cardiomyocyte damage.

PMID- 20811388
TI  - Mutations in CLDN14 are associated with different hearing thresholds.
AB  - Mutations in CLDN14, encoding tight junction protein claudin 14, cause profound
      deafness in mice and humans. We identified a Pakistani family, in which the
      affected individuals were homozygous for a known pathogenic mutation c.254 T>A
      resulting in p.V85D substitution in CLDN14; however, in contrast to the
      previously reported families with mutations in CLDN14, most of the affected
      individuals in this family exhibit only a severe hearing loss (HL). In order to
      identify the contribution of CLDN14 to less than profound deafness, we screened
      for mutations of CLDN14 in 30 multiplex and 57 sporadic cases with moderately
      severe to severe HL from Pakistan. We identified one other affected individual
      homozygous for p.V85D substitution. Comparison of audiometric data from all
      patients indicates that mutations in CLND14 cause varying degrees of HL, which
      may be enhanced at high frequencies. This suggests that a modifier can reduce the
      severity of HL associated with mutations of CLDN14. Our data indicate that
      mutations in CLDN14 should be explored when considering the etiology of less
      severe HL.

PMID- 20811389
TI  - Association between neuropeptide Y receptor 2 polymorphism and the smoking
      behavior of elderly Japanese.
AB  - Molecular heterogeneity of neuropeptide Y (NPY) and its three receptors (1, 2 and
      5) has recently been discovered. NPY2R polymorphisms have been shown to be
      related to cocaine and alcohol dependence in European Americans. To test our
      hypothesis that these polymorphisms influence the smoking behavior of Japanese
      population, we investigated the prevalence of the rs4425326 and rs6857715
      polymorphisms, which have been suggested to be related to alcohol dependence in
      European Americans, in 2517 Japanese elderly subjects for whom information on
      smoking behaviors was available. The prevalence of current smokers was greater
      among Japanese men having the rs4425326 C allele than ex-smokers. Among the ever
      smokers, the Fagerstrom Test for Nicotine Dependence scores were higher in men
      having the rs4425326 homozygous T allelotype, and the numbers of cigarettes
      smoked per day were also significantly higher in the male smokers having the TT
      genotype. No correlations between the Tobacco Dependence Screener scores and any
      genotypes were detected. These results suggest that rs4425326 polymorphism may be
      related to smoking behavior in the Japanese elderly population. This study for
      the first time suggests NPY2R genotype as a possible genetic factor in nicotine
      dependence.

PMID- 20811390
TI  - Prevalence of erectile dysfunction among Chinese men with type 2 diabetes
      mellitus.
AB  - The aims of this study were to investigate the prevalence of ED in Chinese men
      with type 2 diabetes mellitus, and evaluate the efficacy and safety of sildenafil
      citrate in these patients. Patients from 42 outpatient diabetes clinics with type
      2 diabetes mellitus and ED as defined by the International Index of Erectile
      Function (IIEF)-5 were studied. Participants with ED received three doses (100 mg
      each) of sildenafil citrate for use over 3 months. Efficacy of sildenafil citrate
      was assessed using the IIEF-5 and the Global Efficacy Questionnaire (GEQ).
      Adverse events were recorded by patients in a daily diary. A total of 5477
      participants were evaluated, and 75.2% had ED. Age, duration of diabetes and
      glycosylated hemoglobin (HbA(1)c) >6.5% were independently and significantly
      associated with the presence and degree of ED. Patients who received
      pharmacotherapy (N=389) reported significant improvements. The rate of erections
      as determined by the GEQ was also significantly improved following treatment. ED
      is a common complication in Chinese men with type 2 diabetes mellitus, and
      certain risk factors are associated with the presence of ED and severity.
      Sildenafil citrate is a safe and effective treatment for these patients.

PMID- 20811391
TI  - Traumatic central cord syndrome.

PMID- 20811392
TI  - Stat3 as a therapeutic target for the treatment of psoriasis: a clinical
      feasibility study with STA-21, a Stat3 inhibitor.
AB  - Epidermal keratinocytes in psoriatic lesions are characterized by activated
      Stat3, and increased levels of cytokines and growth factors that promote Stat3
      activation have been found within psoriatic lesions. K5.Stat3C transgenic mice,
      in which keratinocytes express a constitutively active Stat3, develop psoriasis
      like skin lesions. In this study, we examined whether STA-21, a small Stat3
      inhibitor, could be useful in ameliorating the skin lesions not only in the model
      mouse but also in human psoriasis. Treatment with STA-21 markedly inhibited the
      cytokine-dependent nuclear translocation of Stat3 in normal human keratinocytes
      in vitro. Keratinocyte proliferation was inhibited by STA-21 in a dose-dependent
      manner through downregulation of c-Myc and cyclin D1, whereas involucrin,
      transglutaminase 1, and keratin 10 levels were upregulated. Topical application
      of STA-21 abolished the generation of skin lesions in K5.Stat3C mice. Finally, we
      treated psoriasis patients with STA-21-containing ointment in a nonrandomized
      study. Psoriatic lesions in six of the eight patients showed improvement after
      topical STA-21 treatment for 2 weeks. Therefore, we conclude that targeting Stat3
      may lead to a therapy for psoriasis.

PMID- 20811394
TI  - Inhibition of NF-kappaB signaling retards eosinophilic dermatitis in SHARPIN
      deficient mice.
AB  - The NF-kappaB pathway performs pivotal roles in diverse physiological processes
      such as immunity, inflammation, proliferation, and apoptosis. NF-kappaB is kept
      inactive in the cytoplasm through association with inhibitors (IkappaB), and
      translocates to the nucleus to activate its target genes after the IkappaBs are
      phosphorylated and degraded. Here, we demonstrate that loss of function of SHANK
      associated RH domain interacting protein (SHARPIN) leads to activation of NF
      kappaB signaling in skin, resulting in the development of an idiopathic
      hypereosinophilic syndrome (IHES) with eosinophilic dermatitis in C57BL/KaLawRij
      Sharpin(cpdm)/RijSunJ mice, and clonal expansion of B-1 B cells and CD3(+)CD4(
      )CD8(-) T cells. Transcription profiling in skin revealed constitutive activation
      of classical NF-kappaB pathways, predominantly by overexpressed members of IL1
      family. Compound-null mutants for both the IL1 receptor accessory protein
      (Il1rap(tm1Roml)) and SHARPIN (Sharpin(cpdm)) resulted in mice having decreased
      skin disease severity. Inhibition of IkappaBA degradation by the proteasome
      inhibitor bortezomib alleviated the dermatitis in Sharpin(cpdm) mice. These
      results indicate that absence of SHARPIN causes IHES with eosinophilic dermatitis
      by NF-kappaB activation, and bortezomib may be an effective treatment for skin
      problems of IHES.

PMID- 20811395
TI  - Decreased concentration and enhanced metabolism of sphingosine-1-phosphate in
      lesional skin of dogs with atopic dermatitis: disturbed sphingosine-1-phosphate
      homeostasis in atopic dermatitis.

PMID- 20811396
TI  - Fibronectin growth factor-binding domains are required for fibroblast survival.
AB  - Fibronectin (FN) is required for embryogenesis, morphogenesis, and wound repair,
      and its Arg-Gly-Asp-containing central cell-binding domain (CCBD) is essential
      for mesenchymal cell survival and growth. Here, we demonstrate that FN contains
      three growth factor-binding domains (FN-GFBDs) that bind platelet-derived growth
      factor-BB (PDGF-BB), a potent fibroblast survival and mitogenic factor. These
      sites bind PDGF-BB with dissociation constants of 10-100 nM. FN-null cells
      cultured on recombinant CCBD (FNIII(8-11)) without a FN-GFBD demonstrated minimal
      metabolism and underwent autophagy at 24 hours, followed by apoptosis at 72
      hours, even in the presence of PDGF-BB. In contrast, FN-null cells plated on
      FNIII(8-11) contiguous with FN-GFBD survived without, and proliferated with, PDGF
      BB. FN-null cell survival on FNIII(8-11) and noncontiguous arrays of FN-GFBDs
      required these domains to be adsorbed on the same surface, suggesting the
      existence of a mesenchymal cell-extracellular matrix synapse. Thus, fibroblast
      survival required GF stimulation in the presence of a FN-GFBD, as well as
      adhesion to FN through the CCBD. The findings that fibroblast survival is
      dependent on FN-GFBD underscore the critical importance of pericellular matrix
      for cell survival and have significant implications for cutaneous wound healing
      and regeneration.

PMID- 20811397
TI  - Evaluation of the clonidine suppression test in the diagnosis of
      phaeochromocytoma.
AB  - The aim of this study is to review the experience of the clonidine suppression
      test in a regional endocrine centre and to compare the diagnostic sensitivity and
      specificity using various previous published criteria. The design used is
      retrospective study. The subjects include 56 patients in whom clonidine
      suppression tests had been performed from 1995 to 2000: 15 with phaeochromocytoma
      and 41 patients in whom the diagnosis was excluded using a combination of
      biochemical testing, abdominal computed tomography scanning and clinical follow
      up. Plasma catecholamines were measured by high pressure liquid chromatography on
      basal samples and at hourly intervals for 3 h after the administration of
      clonidine 300 MUg orally and the following diagnostic criteria were applied:
      plasma noradrenaline+adrenaline>2.96 nmol l(-1) at 3 h post-clonidine or a
      baseline plasma adrenaline plus noradrenaline>11.82 nmol l(-1); plasma
      noradrenaline>2.96 nmol l(-1) at 3 h post-clonidine and plasma noradrenaline>2.96
      nmol l(-1) and <50% fall in noradrenaline at 3 h post-clonidine. The results
      obtained is that mean plasma noradrenaline plus adrenaline fell across the test
      in 40/41 patients in the non-phaeochromocytoma patients and was lowest at 3 h
      (basal 2.28 +/- 0.14 vs 1.36 +/- 0.11 nmol l(-1), P<0.001). In the
      phaeochromocytoma group, clonidine had a variable effect on adrenaline plus
      noradrenaline levels with increases in 7/15. Using an abnormal result as a 3 h
      level of noradrenaline plus adrenaline>2.96 mmol l(-1) gave a sensitivity of 93%
      and specificity of 95%. When a 3 h noradrenaline>2.96 mmol l(-1) was used,
      sensitivity was 87% and specificity 95%. Using the former criteria, noradrenaline
      plus adrenaline>2.96 mmol l(-1), 1/15 in the phaeochromocytoma group had a normal
      result after clonidine suppression testing. Two of 41 in the non
      phaeochromocytoma group had a false-positive result. Under carefully controlled
      conditions, the clonidine suppression test is well tolerated, safe and accurate
      for use in the investigation of patients with suspected phaeochromocytoma.

PMID- 20811398
TI  - Blood pressure lowering effect of lactotripeptides assumed as functional foods: a
      meta-analysis of current available clinical trials.
AB  - The oral assumption of lactotripeptides Valine-Proline-Proline (VPP) and
      Isoleucine-Proline-Proline (IPP) as nutraceuticals or functional foods is
      supposed to improve blood pressure (BP) control by angiotensin-converting enzyme
      inhibition. However, data derived from clinical trials have reached conflicting
      conclusions. To perform a meta-analysis of placebo-controlled clinical trials
      evaluating the anti-hypertensive effect of lactotripeptides assumed as
      nutraceuticals or functional foods. Trials identified using a defined search
      strategy in PubMed were included in the meta-analysis, and their pooled effect
      was estimated with a random effects model, weighting for the inverse of the
      variance. Heterogeneity, publication bias, subgroup and meta-regression analyses
      were performed. A total of 18 trials have been identified, the clinical data of
      which have been clearly reported. Pooled effect of peptides was a reduction of 
      3.73 mm Hg (95% CI: -6.70, -1.76) for systolic blood pressure (SBP) and 1.97 mm
      Hg (95% CI: -3.85, -0.64) for diastolic blood pressure (DBP). The effect was more
      evident in Asian patients (SBP = -6.93 mm Hg (95% CI: -10.95, -2.94); DBP=-3.98
      mm Hg(95% CI: -5.38, -2.44)) than in Caucasian ones (SBP=-1.17 mm Hg (95% CI: 
      2.82, 0.72); DBP = -0.52 mm Hg (95% CI: -1.39, 0.13)), and apparently not related
      to age, baseline BP values, dose of lactotripeptides assumed or length of the
      treatment. VPP and IPP lactotripeptides assumed as functional foods may
      significantly reduce SBP particularly in Asian subjects. The relevance of this
      findings in other ethnicities or associated with different dietary pattern should
      to be further investigated.

PMID- 20811399
TI  - JAK2 46/1 haplotype analysis in myeloproliferative neoplasms and acute myeloid
      leukemia.

PMID- 20811400
TI  - Targeting base excision repair suggests a new therapeutic strategy of fludarabine
      for the treatment of chronic lymphocytic leukemia.

PMID- 20811401
TI  - Robust in vivo differentiation of t(8;21)-positive acute myeloid leukemia blasts
      to neutrophilic granulocytes induced by treatment with dasatinib.

PMID- 20811402
TI  - Acute myeloid leukemia cells fail to activate native human dendritic cells: a
      potential mechanism of immune evasion.

PMID- 20811403
TI  - Patients with chronic myeloid leukemia who maintain a complete molecular response
      after stopping imatinib treatment have evidence of persistent leukemia by DNA
      PCR.
AB  - Around 40-50% of patients with chronic myeloid leukemia (CML) who achieve a
      stable complete molecular response (CMR; undetectable breakpoint cluster region
      Abelson leukemia gene human homolog 1 (BCR-ABL1) mRNA) on imatinib can stop
      therapy and remain in CMR, at least for several years. This raises the
      possibility that imatinib therapy may not need to be continued indefinitely in
      some CML patients. Two possible explanations for this observation are (1) CML has
      been eradicated or (2) residual leukemic cells fail to proliferate despite the
      absence of ongoing kinase inhibition. We used a highly sensitive patient-specific
      nested quantitative PCR to look for evidence of genomic BCR-ABL1 DNA in patients
      who sustained CMR after stopping imatinib therapy. Seven of eight patients who
      sustained CMR off therapy had BCR-ABL1 DNA detected at least once after stopping
      imatinib, but none has relapsed (follow-up 12-41 months). BCR-ABL1 DNA levels
      increased in all of the 10 patients who lost CMR soon after imatinib cessation,
      whereas serial testing of patients in sustained CMR showed a stable level of BCR
      ABL1 DNA. This more sensitive assay for BCR-ABL1 provides evidence that even
      patients who maintain a CMR after stopping imatinib may harbor residual leukemia.
      A search for intrinsic or extrinsic (for example, immunological) causes for this
      drug-free leukemic suppression is now indicated.

PMID- 20811405
TI  - Comment on 'Integrative genomic profiling of human prostate cancer'.

PMID- 20811406
TI  - OCT-1 activity measurement provides a superior imatinib response predictor than
      screening for single-nucleotide polymorphisms of OCT-1.

PMID- 20811404
TI  - The use of biochemical markers of bone remodeling in multiple myeloma: a report
      of the International Myeloma Working Group.
AB  - Lytic bone disease is a frequent complication of multiple myeloma (MM). Lytic
      lesions rarely heal and X-rays are of limited value in monitoring bone
      destruction during anti-myeloma or anti-resorptive treatment. Biochemical markers
      of bone resorption (amino- and carboxy-terminal cross-linking telopeptide of type
      I collagen (NTX and CTX, respectively) or CTX generated by matrix
      metalloproteinases (ICTP)) and bone formation provide information on bone
      dynamics and reflect disease activity in bone. These markers have been
      investigated as tools for evaluating the extent of bone disease, risk of skeletal
      morbidity and response to anti-resorptive treatment in MM. Urinary NTX, serum CTX
      and serum ICTP are elevated in myeloma patients with osteolytic lesions and
      correlate with advanced disease stage. Furthermore, urinary NTX and serum ICTP
      correlate with risk for skeletal complications, disease progression and overall
      survival. Bone markers have also been used for the early diagnosis of bone
      lesions. This International Myeloma Working Group report summarizes the existing
      data for the role of bone markers in assessing the extent of MM bone disease and
      in monitoring bone turnover during anti-myeloma therapies and provides
      information on novel markers that may be of particular interest in the near
      future.

PMID- 20811407
TI  - Atom gravimeters and gravitational redshift.
AB  - In ref. 1 the authors present a re-interpretation of atom interferometry
      experiments published a decade ago. They now consider the atom interferometry
      experiments as a measurement of the gravitational redshift on the quantum clock
      operating at the Compton frequency omega(C) = mc(2)/ approximately 2pi x 3.0 x
      10(25) Hz, where m is the caesium (Cs) atom rest mass. They then argue that this
      redshift measurement compares favourably with existing as well as projected clock
      tests. Here we show that this interpretation is incorrect.

PMID- 20811411
TI  - How continents persist.

PMID- 20811412
TI  - A law in time?

PMID- 20811409
TI  - Can controversies be put to REST?
AB  - The contribution of REST to embryonic stem (ES) cell pluripotency has been
      uncertain. Two years ago, Singh et al. claimed that Rest(+/-) and REST knock-down
      ES cells expressed reduced levels of pluripotency markers, in contrast to a prior
      and subsequent reports. To understand the basis of this difference, we analysed
      the YHC334 (YHC) and RRC160 (RRC) gene-trap ES cell lines used by Singh et al.,
      obtained directly from BayGenomics. Both REST mutant lines generated REST-betaGeo
      fusion proteins, but expressed pluripotency genes at levels similar to
      appropriately matched parental wild ES cells, consistent with expression being
      REST-independent.

PMID- 20811422
TI  - Journal club. A materials scientist comments on two methods for three-dimensional
      nanofabrication.

PMID- 20811426
TI  - Climate panel must adapt to survive.

PMID- 20811425
TI  - Stem-cell work thrown into limbo.

PMID- 20811427
TI  - Ecologists fear Antarctic krill crisis.

PMID- 20811428
TI  - The mystery of the missing oil plume.

PMID- 20811429
TI  - Cold blamed for Bolivia's mass fish deaths.

PMID- 20811430
TI  - Nanotechnology: Small wonders.

PMID- 20811431
TI  - Deepwater Horizon: After the oil.

PMID- 20811432
TI  - World view: Politicize me.

PMID- 20811433
TI  - Games and play mean different things in an educational context.

PMID- 20811434
TI  - Stem-cell decision is no threat to federal science funding.

PMID- 20811435
TI  - Irish research cuts threaten economic recovery.

PMID- 20811436
TI  - Mosquitoes: more likely nectar thieves than pollinators.

PMID- 20811437
TI  - Seafood stewardship in crisis.

PMID- 20811442
TI  - Biological physics: Filaments band together.

PMID- 20811443
TI  - Microbiology: Altruistic defence.

PMID- 20811444
TI  - Astrophysics: Unexpected warm water.

PMID- 20811445
TI  - Alzheimer's disease: Selectively tuning gamma-secretase.

PMID- 20811446
TI  - Laser science: Suckers for light.

PMID- 20811447
TI  - Regenerative medicine: Heart redevelopment.

PMID- 20811449
TI  - Obituary: Donald Charles Backer (1943-2010).

PMID- 20811450
TI  - The impacts of climate change on water resources and agriculture in China.
AB  - China is the world's most populous country and a major emitter of greenhouse
      gases. Consequently, much research has focused on China's influence on climate
      change but somewhat less has been written about the impact of climate change on
      China. China experienced explosive economic growth in recent decades, but with
      only 7% of the world's arable land available to feed 22% of the world's
      population, China's economy may be vulnerable to climate change itself. We find,
      however, that notwithstanding the clear warming that has occurred in China in
      recent decades, current understanding does not allow a clear assessment of the
      impact of anthropogenic climate change on China's water resources and agriculture
      and therefore China's ability to feed its people. To reach a more definitive
      conclusion, future work must improve regional climate simulations-especially of
      precipitation-and develop a better understanding of the managed and unmanaged
      responses of crops to changes in climate, diseases, pests and atmospheric
      constituents.

PMID- 20811452
TI  - Neurotrophin receptors TrkA and TrkC cause neuronal death whereas TrkB does not.
AB  - Neurons of the peripheral nervous system have long been known to require survival
      factors to prevent their death during development. But why they selectively
      become dependent on secretory molecules has remained a mystery, as is the
      observation that in the central nervous system, most neurons do not show this
      dependency. Using engineered embryonic stem cells, we show here that the
      neurotrophin receptors TrkA and TrkC (tropomyosin receptor kinase A and C, also
      known as Ntrk1 and Ntrk3, respectively) instruct developing neurons to die, both
      in vitro and in vivo. By contrast, TrkB (also known as Ntrk2), a closely related
      receptor primarily expressed in the central nervous system, does not. These
      results indicate that TrkA and TrkC behave as dependence receptors, explaining
      why developing sympathetic and sensory neurons become trophic-factor-dependent
      for survival. We suggest that the expansion of the Trk gene family that
      accompanied the segregation of the peripheral from the central nervous system
      generated a novel mechanism of cell number control.

PMID- 20811451
TI  - Integrating common and rare genetic variation in diverse human populations.
AB  - Despite great progress in identifying genetic variants that influence human
      disease, most inherited risk remains unexplained. A more complete understanding
      requires genome-wide studies that fully examine less common alleles in
      populations with a wide range of ancestry. To inform the design and
      interpretation of such studies, we genotyped 1.6 million common single nucleotide
      polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations,
      and sequenced ten 100-kilobase regions in 692 of these individuals. This
      integrated data set of common and rare alleles, called 'HapMap 3', includes both
      SNPs and copy number polymorphisms (CNPs). We characterized population-specific
      differences among low-frequency variants, measured the improvement in imputation
      accuracy afforded by the larger reference panel, especially in imputing SNPs with
      a minor allele frequency of <or=5%, and demonstrated the feasibility of imputing
      newly discovered CNPs and SNPs. This expanded public resource of genome variants
      in global populations supports deeper interrogation of genomic variation and its
      role in human disease, and serves as a step towards a high-resolution map of the
      landscape of human genetic variation.

PMID- 20811453
TI  - Warm water vapour in the sooty outflow from a luminous carbon star.
AB  - The detection of circumstellar water vapour around the ageing carbon star IRC
      +10216 challenged the current understanding of chemistry in old stars, because
      water was predicted to be almost absent in carbon-rich stars. Several
      explanations for the water were postulated, including the vaporization of icy
      bodies (comets or dwarf planets) in orbit around the star, grain surface
      reactions, and photochemistry in the outer circumstellar envelope. With a single
      water line detected so far from this one carbon-rich evolved star, it is
      difficult to discriminate between the different mechanisms proposed. Here we
      report the detection of dozens of water vapour lines in the far-infrared and sub
      millimetre spectrum of IRC +10216 using the Herschel satellite. This includes
      some high-excitation lines with energies corresponding to approximately 1,000 K,
      which can be explained only if water is present in the warm inner sooty region of
      the envelope. A plausible explanation for the warm water appears to be the
      penetration of ultraviolet photons deep into a clumpy circumstellar envelope.
      This mechanism also triggers the formation of other molecules, such as ammonia,
      whose observed abundances are much higher than hitherto predicted.

PMID- 20811454
TI  - Polar patterns of driven filaments.
AB  - The emergence of collective motion exhibited by systems ranging from flocks of
      animals to self-propelled microorganisms to the cytoskeleton is a ubiquitous and
      fascinating self-organization phenomenon. Similarities between these systems,
      such as the inherent polarity of the constituents, a density-dependent transition
      to ordered phases or the existence of very large density fluctuations, suggest
      universal principles underlying pattern formation. This idea is followed by
      theoretical models at all levels of description: micro- or mesoscopic models
      directly map local forces and interactions using only a few, preferably simple,
      interaction rules, and more macroscopic approaches in the hydrodynamic limit rely
      on the systems' generic symmetries. All these models characteristically have a
      broad parameter space with a manifold of possible patterns, most of which have
      not yet been experimentally verified. The complexity of interactions and the
      limited parameter control of existing experimental systems are major obstacles to
      our understanding of the underlying ordering principles. Here we demonstrate the
      emergence of collective motion in a high-density motility assay that consists of
      highly concentrated actin filaments propelled by immobilized molecular motors in
      a planar geometry. Above a critical density, the filaments self-organize to form
      coherently moving structures with persistent density modulations, such as
      clusters, swirls and interconnected bands. These polar nematic structures are
      long lived and can span length scales orders of magnitudes larger than their
      constituents. Our experimental approach, which offers control of all relevant
      system parameters, complemented by agent-based simulations, allows backtracking
      of the assembly and disassembly pathways to the underlying local interactions. We
      identify weak and local alignment interactions to be essential for the observed
      formation of patterns and their dynamics. The presented minimal polar-pattern
      forming system may thus provide new insight into emerging order in the broad
      class of active fluids and self-propelled particles.

PMID- 20811455
TI  - Olivine water contents in the continental lithosphere and the longevity of
      cratons.
AB  - Cratons, the ancient cores of continents, contain the oldest crust and mantle on
      the Earth (>2 Gyr old). They extend laterally for hundreds of kilometres, and are
      underlain to depths of 180-250 km by mantle roots that are chemically and
      physically distinct from the surrounding mantle. Forming the thickest lithosphere
      on our planet, they act as rigid keels isolated from the flowing asthenosphere;
      however, it has remained an open question how these large portions of the mantle
      can stay isolated for so long from mantle convection. Key physical properties
      thought to contribute to this longevity include chemical buoyancy due to high
      degrees of melt-depletion and the stiffness imparted by the low temperatures of a
      conductive thermal gradient. Geodynamic calculations, however, suggest that these
      characteristics are not sufficient to prevent the lithospheric mantle from being
      entrained during mantle convection over billions of years. Differences in water
      content are a potential source of additional viscosity contrast between cratonic
      roots and ambient mantle owing to the well-established hydrolytic weakening
      effect in olivine, the most abundant mineral of the upper mantle. However, the
      water contents of cratonic mantle roots have to date been poorly constrained.
      Here we show that olivine in peridotite xenoliths from the lithosphere
      asthenosphere boundary region of the Kaapvaal craton mantle root are water-poor
      and provide sufficient viscosity contrast with underlying asthenosphere to
      satisfy the stability criteria required by geodynamic calculations. Our results
      provide a solution to a puzzling mystery of plate tectonics, namely why the
      oldest continents, in contrast to short-lived oceanic plates, have resisted
      recycling into the interior of our tectonically dynamic planet.

PMID- 20811456
TI  - Bacterial charity work leads to population-wide resistance.
AB  - Bacteria show remarkable adaptability in the face of antibiotic therapeutics.
      Resistance alleles in drug target-specific sites and general stress responses
      have been identified in individual end-point isolates. Less is known, however,
      about the population dynamics during the development of antibiotic-resistant
      strains. Here we follow a continuous culture of Escherichia coli facing
      increasing levels of antibiotic and show that the vast majority of isolates are
      less resistant than the population as a whole. We find that the few highly
      resistant mutants improve the survival of the population's less resistant
      constituents, in part by producing indole, a signalling molecule generated by
      actively growing, unstressed cells. We show, through transcriptional profiling,
      that indole serves to turn on drug efflux pumps and oxidative-stress protective
      mechanisms. The indole production comes at a fitness cost to the highly resistant
      isolates, and whole-genome sequencing reveals that this bacterial altruism is
      made possible by drug-resistance mutations unrelated to indole production. This
      work establishes a population-based resistance mechanism constituting a form of
      kin selection whereby a small number of resistant mutants can, at some cost to
      themselves, provide protection to other, more vulnerable, cells, enhancing the
      survival capacity of the overall population in stressful environments.

PMID- 20811457
TI  - A spindle-independent cleavage furrow positioning pathway.
AB  - The mitotic spindle determines the cleavage furrow site during metazoan cell
      division, but whether other mechanisms exist remains unknown. Here we identify a
      spindle-independent mechanism for cleavage furrow positioning in Drosophila
      neuroblasts. We show that early and late furrow proteins (Pavarotti, Anillin, and
      Myosin) are localized to the neuroblast basal cortex at anaphase onset by a Pins
      cortical polarity pathway, and can induce a basally displaced furrow even in the
      complete absence of a mitotic spindle. Rotation or displacement of the spindle
      results in two furrows: an early polarity-induced basal furrow and a later
      spindle-induced furrow. This spindle-independent cleavage furrow mechanism may be
      relevant to other highly polarized mitotic cells, such as mammalian neural
      progenitors.

PMID- 20811458
TI  - Gamma-secretase activating protein is a therapeutic target for Alzheimer's
      disease.
AB  - Accumulation of neurotoxic amyloid-beta is a major hallmark of Alzheimer's
      disease. Formation of amyloid-beta is catalysed by gamma-secretase, a protease
      with numerous substrates. Little is known about the molecular mechanisms that
      confer substrate specificity on this potentially promiscuous enzyme. Knowledge of
      the mechanisms underlying its selectivity is critical for the development of
      clinically effective gamma-secretase inhibitors that can reduce amyloid-beta
      formation without impairing cleavage of other gamma-secretase substrates,
      especially Notch, which is essential for normal biological functions. Here we
      report the discovery of a novel gamma-secretase activating protein (GSAP) that
      drastically and selectively increases amyloid-beta production through a mechanism
      involving its interactions with both gamma-secretase and its substrate, the
      amyloid precursor protein carboxy-terminal fragment (APP-CTF). GSAP does not
      interact with Notch, nor does it affect its cleavage. Recombinant GSAP stimulates
      amyloid-beta production in vitro. Reducing GSAP concentrations in cell lines
      decreases amyloid-beta concentrations. Knockdown of GSAP in a mouse model of
      Alzheimer's disease reduces levels of amyloid-beta and plaque development. GSAP
      represents a type of gamma-secretase regulator that directs enzyme specificity by
      interacting with a specific substrate. We demonstrate that imatinib, an
      anticancer drug previously found to inhibit amyloid-beta formation without
      affecting Notch cleavage, achieves its amyloid-beta-lowering effect by preventing
      GSAP interaction with the gamma-secretase substrate, APP-CTF. Thus, GSAP can
      serve as an amyloid-beta-lowering therapeutic target without affecting other key
      functions of gamma-secretase.

PMID- 20811459
TI  - Genome-wide measurement of RNA secondary structure in yeast.
AB  - The structures of RNA molecules are often important for their function and
      regulation, yet there are no experimental techniques for genome-scale measurement
      of RNA structure. Here we describe a novel strategy termed parallel analysis of
      RNA structure (PARS), which is based on deep sequencing fragments of RNAs that
      were treated with structure-specific enzymes, thus providing simultaneous in
      vitro profiling of the secondary structure of thousands of RNA species at single
      nucleotide resolution. We apply PARS to profile the secondary structure of the
      messenger RNAs (mRNAs) of the budding yeast Saccharomyces cerevisiae and obtain
      structural profiles for over 3,000 distinct transcripts. Analysis of these
      profiles reveals several RNA structural properties of yeast transcripts,
      including the existence of more secondary structure over coding regions compared
      with untranslated regions, a three-nucleotide periodicity of secondary structure
      across coding regions and an anti-correlation between the efficiency with which
      an mRNA is translated and the structure over its translation start site. PARS is
      readily applicable to other organisms and to profiling RNA structure in diverse
      conditions, thus enabling studies of the dynamics of secondary structure at a
      genomic scale.

PMID- 20811460
TI  - Mechanism of the ATP-dependent DNA end-resection machinery from Saccharomyces
      cerevisiae.
AB  - If not properly processed and repaired, DNA double-strand breaks (DSBs) can give
      rise to deleterious chromosome rearrangements, which could ultimately lead to the
      tumour phenotype. DSB ends are resected in a 5' to 3' fashion in cells, to yield
      single-stranded DNA (ssDNA) for the recruitment of factors critical for DNA
      damage checkpoint activation and repair by homologous recombination. The
      resection process involves redundant pathways consisting of nucleases, DNA
      helicases and associated proteins. Being guided by recent genetic studies, we
      have reconstituted the first eukaryotic ATP-dependent DNA end-resection machinery
      comprising the Saccharomyces cerevisiae Mre11-Rad50-Xrs2 (MRX) complex, the Sgs1
      Top3-Rmi1 complex, Dna2 protein and the heterotrimeric ssDNA-binding protein RPA.
      Here we show that DNA strand separation during end resection is mediated by the
      Sgs1 helicase function, in a manner that is enhanced by Top3-Rmi1 and MRX. In
      congruence with genetic observations, although the Dna2 nuclease activity is
      critical for resection, the Mre11 nuclease activity is dispensable. By examining
      the top3 Y356F allele and its encoded protein, we provide evidence that the
      topoisomerase activity of Top3, although critical for the suppression of
      crossover recombination, is not needed for resection either in cells or in the
      reconstituted system. Our results also unveil a multifaceted role of RPA, in the
      sequestration of ssDNA generated by DNA unwinding, enhancement of 5' strand
      incision, and protection of the 3' strand. Our reconstituted system should serve
      as a useful model for delineating the mechanistic intricacy of the DNA break
      resection process in eukaryotes.

PMID- 20811463
TI  - Cortical malformations: unfolding polymicrogyria.

PMID- 20811461
TI  - DNA end resection by Dna2-Sgs1-RPA and its stimulation by Top3-Rmi1 and Mre11
      Rad50-Xrs2.
AB  - The repair of DNA double-strand breaks (DSBs) by homologous recombination
      requires processing of broken ends. For repair to start, the DSB must first be
      resected to generate a 3'-single-stranded DNA (ssDNA) overhang, which becomes a
      substrate for the DNA strand exchange protein, Rad51 (ref. 1). Genetic studies
      have implicated a multitude of proteins in the process, including helicases,
      nucleases and topoisomerases. Here we biochemically reconstitute elements of the
      resection process and reveal that it requires the nuclease Dna2, the RecQ-family
      helicase Sgs1 and the ssDNA-binding protein replication protein-A (RPA). We
      establish that Dna2, Sgs1 and RPA constitute a minimal protein complex capable of
      DNA resection in vitro. Sgs1 helicase unwinds the DNA to produce an intermediate
      that is digested by Dna2, and RPA stimulates DNA unwinding by Sgs1 in a species
      specific manner. Interestingly, RPA is also required both to direct Dna2
      nucleolytic activity to the 5'-terminated strand of the DNA break and to inhibit
      3' to 5' degradation by Dna2, actions that generate and protect the 3'-ssDNA
      overhang, respectively. In addition to this core machinery, we establish that
      both the topoisomerase 3 (Top3) and Rmi1 complex and the Mre11-Rad50-Xrs2 complex
      (MRX) have important roles as stimulatory components. Stimulation of end
      resection by the Top3-Rmi1 heterodimer and the MRX proteins is by complex
      formation with Sgs1 (refs 5, 6), which unexpectedly stimulates DNA unwinding. We
      suggest that Top3-Rmi1 and MRX are important for recruitment of the Sgs1-Dna2
      complex to DSBs. Our experiments provide a mechanistic framework for
      understanding the initial steps of recombinational DNA repair in eukaryotes.

PMID- 20811464
TI  - Multiple sclerosis: is multiple sclerosis caused by venous insufficiency?

PMID- 20811465
TI  - Stroke: sedation and anesthesia during endovascular stroke therapy.

PMID- 20811466
TI  - Epilepsy: drug trial design and epilepsy surgery: time for a change?

PMID- 20811467
TI  - Targeting tumor gene by shRNA-expressing Salmonella-mediated RNAi.
AB  - RNA interference (RNAi) has been established as an important research tool that
      carries great potential for gene therapy. However, targeted induction of RNAi in
      vivo has met with significant challenges. In this study, a novel pSLS plasmid
      capable of expressing short hairpin RNAs (shRNAs) was transformed into attenuated
      Salmonella enterica serovar typhimurium strain 7207 (SL). In vitro infection
      studies with the transformed S. enterica containing pSLS (SL-pSLS-CAT)
      demonstrated that expression of shRNA targeting the CTNNB1 gene induced potent
      and specific silencing of CTNNB1 expression in cultured SW480 cells. CTNNB1
      knockdown in SW480 cells was associated with markedly reduced proliferation and
      cell death compared with that of control infected cells. In addition, SL-pSLS-CAT
      mediated CTNNB1 knockdown markedly reduced tumor growth in SW480 xenograft mice.
      These tumors exhibited reduced levels of CTNNB1, as well as c-Myc and cyclin D1.
      Finally, SL-pSLS-CAT treatment also resulted in reduced expression levels of
      these genes in polyps, mucosal tissues and in small intestines of APC(Min) mice.
      Taken together, these data suggest that attenuated shRNA-expressing Salmonella
      may be a powerful new tool for in vitro gene silencing, functional genomics, and
      the development of RNAi-based anticancer or human immunodeficiency virus
      therapeutics.

PMID- 20811468
TI  - Direct and long-term detection of gene doping in conventional blood samples.
AB  - The misuse of somatic gene therapy for the purpose of enhancing athletic
      performance is perceived as a coming threat to the world of sports and
      categorized as 'gene doping'. This article describes a direct detection approach
      for gene doping that gives a clear yes-or-no answer based on the presence or
      absence of transgenic DNA in peripheral blood samples. By exploiting a priming
      strategy to specifically amplify intronless DNA sequences, we developed PCR
      protocols allowing the detection of very small amounts of transgenic DNA in
      genomic DNA samples to screen for six prime candidate genes. Our detection
      strategy was verified in a mouse model, giving positive signals from minute
      amounts (20 MUl) of blood samples for up to 56 days following intramuscular adeno
      associated virus-mediated gene transfer, one of the most likely candidate vector
      systems to be misused for gene doping. To make our detection strategy amenable
      for routine testing, we implemented a robust sample preparation and processing
      protocol that allows cost-efficient analysis of small human blood volumes (200
      MUl) with high specificity and reproducibility. The practicability and
      reliability of our detection strategy was validated by a screening approach
      including 327 blood samples taken from professional and recreational athletes
      under field conditions.

PMID- 20811469
TI  - Use of human MAR elements to improve retroviral vector production.
AB  - Retroviral vectors have many favorable properties for gene therapies, but their
      use remains limited by safety concerns and/or by relatively lower titers for some
      of the safer self-inactivating (SIN) derivatives. In this study, we evaluated
      whether increased production of SIN retroviral vectors can be achieved from the
      use of matrix attachment region (MAR) epigenetic regulators. Two MAR elements of
      human origin were found to increase and to stabilize the expression of the green
      fluorescent protein transgene in stably transfected HEK-293 packaging cells.
      Introduction of one of these MAR elements in retroviral vector-producing plasmids
      yielded higher expression of the viral vector RNA. Consistently, viral titers
      obtained from transient transfection of MAR-containing plasmids were increased up
      to sixfold as compared with the parental construct, when evaluated in different
      packaging cell systems and transfection conditions. Thus, use of MAR elements
      opens new perspectives for the efficient generation of gene therapy vectors.

PMID- 20811470
TI  - Ecological succession in long-term experimentally evolved biofilms produces
      synergistic communities.
AB  - Many biofilm populations are known for their exceptional biodiversity, but the
      relative contributions of the forces that could produce this diversity are poorly
      understood. This uncertainty grows in the old, well-established communities found
      on many natural surfaces and in long-term, chronic infections. If the prevailing
      interactions among species within biofilms are positive, productivity should
      increase with diversity, but if they tend towards competition or antagonism,
      productivity should decrease. Here, we describe the parallel evolution of
      synergistic communities derived from a clone of Burkholderia cenocepacia during
      ~1500 generations of biofilm selection. This long-term evolution was enabled by a
      new experimental method that selects for daily cycles of colonization, biofilm
      assembly and dispersal. Each of the six replicate biofilm populations underwent a
      common pattern of adaptive morphological diversification, in which three
      ecologically distinct morphotypes arose in the same order of succession and
      persisted. In two focal populations, mixed communities were more productive than
      any monoculture and each variant benefited from the mixture. These gains in
      output resulted from asymmetrical cross-feeding between ecotypes and the
      expansion and partitioning of biofilm space that constructed new niches.
      Therefore, even in the absence of starting genetic variation, prolonged selection
      for surface colonization generates a dynamic of ecological succession that
      enhances productivity.

PMID- 20811471
TI  - Changes in sulfate-reducing bacterial populations during the onset of black band
      disease.
AB  - Factors that facilitate the onset of black band disease (BBD) of corals remain
      elusive, though anoxic conditions under the complex microbial mat and production
      of sulfide are implicated in necrosis of underlying coral tissues. This study
      investigated the diversity and quantitative shifts of sulfate-reducing bacterial
      (SRB) populations during the onset of BBD using real-time PCR (RT-PCR) and
      cloning approaches targeting the dissimilatory (bi)sulfite reductase (dsrA) gene.
      A quantitative-PCR (qPCR) assay targeting the 16S rRNA gene also provided an
      estimate of total bacteria, and allowed the relative percentage of SRB within the
      lesions to be determined. Three Montipora sp. coral colonies identified with
      lesions previously termed cyanobacterial patches (CPs) (comprising microbial
      communities unlike those of BBD lesions), were tagged and followed through time
      as CP developed into BBD. The dsrA-targeted qPCR detected few copies of the gene
      in the CP samples (<65 per ng DNA), though copy numbers increased in BBD lesions
      (>2500 per ng DNA). SRB in CP samples were less than 1% of the bacterial
      population, though represented up to 7.5% of the BBD population. Clone libraries
      also demonstrated a shift in the dominant dsrA sequences as lesions shifted from
      CP into BBD. Results from this study confirm that SRB increase during the onset
      of BBD, likely increasing sulfide concentrations at the base of the microbial mat
      and facilitating the pathogenesis of BBD.

PMID- 20811472
TI  - Functional genomic analysis of an uncultured delta-proteobacterium in the sponge
      Cymbastela concentrica.
AB  - Marine sponges are ancient, sessile, filter-feeding metazoans, which represent a
      significant component of the benthic communities throughout the world. Sponges
      harbor a remarkable diversity of bacteria, however, little is known about the
      functional properties of such bacterial symbionts. In this study, we present the
      genomic and functional characterization of an uncultured delta-proteobacterium
      associated with the sponge Cymbastela concentrica. We show that this organism
      represents a novel phylogenetic clade and propose that it lives in association
      with a cyanobacterium. We also provide an overview of the predicted functional
      and ecological properties of this delta-proteobacterium, and discuss its complex
      interactions with surrounding cells and milieu, including traits of cell
      attachment, nutrient transport and protein-protein interactions.

PMID- 20811473
TI  - Microbial community structures in anoxic freshwater lake sediment along a metal
      contamination gradient.
AB  - Contamination, such as by heavy metals, has frequently been implicated in
      altering microbial community structure. However, this association has not been
      extensively studied for anaerobic communities, or in freshwater lake sediments.
      We investigated microbial community structure in the metal-contaminated anoxic
      sediments of a eutrophic lake that were impacted over the course of 80 years by
      nearby zinc-smelting activities. Microbial community structure was inferred for
      bacterial, archaeal and eukaryotic populations by evaluating terminal restriction
      fragment length polymorphism (TRFLP) patterns in near-surface sediments collected
      in triplicate from five areas of the lake that had differing levels of metal
      contamination. The majority of the fragments in the bacterial and eukaryotic
      profiles showed no evidence of variation in association with metal contamination
      levels, and diversity revealed by these profiles remained consistent even as
      metal concentrations varied from 3000 to 27,000 mg kg(-1) total Zn, 0.125 to 11.2
      MU pore water Zn and 0.023 to 5.40 MUM pore water As. Although most archaeal
      fragments also showed no evidence of variation, the prevalence of a fragment
      associated with mesophilic Crenarchaeota showed significant positive correlation
      with total Zn concentrations. This Crenarchaeota fragment dominated the archaeal
      TRFLP profiles, representing between 35% and 79% of the total measured peak
      areas. Lake DePue 16S rRNA gene sequences corresponding to this TRFLP fragment
      clustered with anaerobic and soil mesophilic Crenarchaeota sequences. Although
      Crenarchaeota have been associated with metal-contaminated groundwater and soils,
      this is a first report (to our knowledge) documenting potential increased
      prevalence of Crenarchaeota associated with elevated levels of metal
      contamination.

PMID- 20811474
TI  - Low bone marrow oxygen tension and hypoxia-inducible factor-1alpha overexpression
      characterize patients with multiple myeloma: role on the transcriptional and
      proangiogenic profiles of CD138(+) cells.

PMID- 20811475
TI  - Neural bases of the non-conscious perception of emotional signals.
AB  - Many emotional stimuli are processed without being consciously perceived. Recent
      evidence indicates that subcortical structures have a substantial role in this
      processing. These structures are part of a phylogenetically ancient pathway that
      has specific functional properties and that interacts with cortical processes.
      There is now increasing evidence that non-consciously perceived emotional stimuli
      induce distinct neurophysiological changes and influence behaviour towards the
      consciously perceived world. Understanding the neural bases of the non-conscious
      perception of emotional signals will clarify the phylogenetic continuity of
      emotion systems across species and the integration of cortical and subcortical
      activity in the human brain.

PMID- 20811476
TI  - Emerging approaches of transcatheter valve repair/insertion.
AB  - Aortic stenosis (AS) and mitral regurgitation (MR) account for the majority of
      valvular diseases and their prevalence is increasing according to increased life
      expectancy. Surgical treatment is the gold standard, although operative risk may
      be high in some patients due to comorbidities and age. A large part of the
      patients at high surgical risk who could beneficiate of treatment are not
      referred to surgery. Therefore, there is a need of alternative and less invasive
      procedures.

PMID- 20811477
TI  - Coupling among electroencephalogram gamma signals on a short time scale.
AB  - An important goal in neuroscience is to identify instances when EEG signals are
      coupled. We employ a method to measure the coupling strength between gamma
      signals (40-100 Hz) on a short time scale as the maximum cross-correlation over a
      range of time lags within a sliding variable-width window. Instances of coupling
      states among several signals are also identified, using a mixed multivariate beta
      distribution to model coupling strength across multiple gamma signals with
      reference to a common base signal. We first apply our variable-window method to
      simulated signals and compare its performance to a fixed-window approach. We then
      focus on gamma signals recorded in two regions of the rat hippocampus. Our
      results indicate that this may be a useful method for mapping coupling patterns
      among signals in EEG datasets.

PMID- 20811478
TI  - Use of Tetra-ammonium Tetrakis(4-Sulphonato)Phenyl Porphyrin for Pseudomonas and
      Bacillus Cell Imaging.
AB  - The use of tetraammonium tetrakis(4-sulphonato)phenyl porphyrin (TPPS), a water
      soluble anionic compound, as a stain to analyse bacterial cells using fluorescent
      microscopy was investigated. TPPS was effectively used to analyse two different
      bacteria: Pseudomonas aeruginosa and Bacillus cereus. The variation in brightness
      with varying concentrations of TPPS was studied. The patterns of variations for
      these bacteria were found to be the same, but with consistently higher brightness
      for Bacillus cereus.

PMID- 20811479
TI  - Life-saving super-urgent liver transplantation with replacement of retrohepatic
      vena cava by dacron graft.
AB  - We describe a modified technique of side-to-side cavo-cavostomy by Dacron
      interposition prosthesis during a super urgent liver transplantation. A liver
      graft from a deceased donor was immediately requested on a top priority basis as
      a consequence of massive bleeding during extended left hepatectomy for a huge
      hepatic haemangioma arising from the caudate lobe. Veno-venous bypass was
      employed during anhepatic phase but it was disconnected due to severe
      fibrinolysis and hypothermia. A porto-caval shunt was performed and the inferior
      vena cava outflow was restored by a Dacron interposition prosthesis. A liver
      graft from a deceased donor was available 16 hours later. Due to the shortness of
      the vena cava of the donor liver graft, the removal of the Dacron graft was
      impossible and a modified side-to-side cavo-cavostomy between the Dacron
      interposition graft and the vena cava of the donor liver was than performed.
      Liver transplantation was uneventful and the patient is doing well 25 months
      after the surgical procedure. Although the use of synthetic vascular prosthesis
      should usually be discouraged during organ transplantation, its exceptional use
      during liver transplantation is possible with long-term good results.

PMID- 20811480
TI  - The initial immune reaction to a new tumor antigen is always stimulatory and
      probably necessary for the tumor's growth.
AB  - All nascent neoplasms probably elicit at least a weak immune reaction. However,
      the initial effect of the weak immune reaction on a nascent tumor is always
      stimulatory rather than inhibitory to tumor growth, assuming only that exposure
      to the tumor antigens did not antedate the initiation of the neoplasm (as may
      occur in some virally induced tumors). This conclusion derives from the
      observation that the relationship between the magnitude of an adaptive immune
      reaction and tumor growth is not linear but varies such that while large
      quantities of antitumor immune reactants tend to inhibit tumor growth, smaller
      quantities of the same reactants are, for unknown reasons, stimulatory. Any
      immune reaction must presumably be small before it can become large; hence the
      initial reaction to the first presentation of a tumor antigen must always be
      small and in the stimulatory portion of this nonlinear relationship. In mouse
      skin carcinogenesis experiments it was found that premalignant papillomas were
      variously immunogenic, but that the carcinomas that arose in them were,
      presumably because of induced immune tolerance, nonimmunogenic in the animal of
      origin.

PMID- 20811481
TI  - Dermoscopy of rippled pattern sebaceoma.
AB  - A 77-year-old Japanese woman presented a dome-shaped pinkish nodule on the scalp.
      Dermoscopy demonstrated yellowish homogeneous ovoid areas with translucent
      whitish veil and arborizing vessels. No association with Muir-Torre syndrome was
      found. Histopathology revealed a smooth-bordered neoplasm in the dermis with
      partial connection to the epidermis. The tumor was composed mainly of germinative
      cells. The tumor focally showed a typical "rippled pattern". There were only a
      few vacuolated cells suggesting sebaceous differentiation. These cells were
      highlighted with adipophilin antibody. No nuclear atypia or mitotic figures were
      observed. We regarded the neoplasm as sebaceoma. Dermoscopy demonstrated clearly
      visualized yellowish homogeneous ovoid areas. This feature usually corresponds to
      dermal conglomerations of the cells with sebaceous differentiation. However, this
      case histopathologically showed only limited area with sebaceous differentiation.
      We presented a case of rippled-pattern sebaceoma and described its dermoscopic
      features. This was the first report referring to the dermoscopic features of
      sebaceoma.

PMID- 20811482
TI  - Factors to improve the management of hepatitis C in drug users: an observational
      study in an addiction centre.
AB  - Barriers to management of HCV in injection drug users are related to patients,
      health providers, and facilities. In a primary care drug user's addiction centre
      we studied access to HCV standard of care before and after using an onsite total
      care concept provided by a multidisciplinary team and noninvasive liver fibrosis
      evaluation. A total of 586 patients were seen between 2002 and 2004. The
      majority, 417 patients, were HCV positive and of these patients 337 were tested
      positive for HCV RNA. In 2002, patients were sent to the hospital. with the
      Starting of 2003, patients were offered standard of care HCV management in the
      center by a team of general practitioners, a consultant hepatologist,
      psychiatrists, nurses, and a health counsellor. Liver fibrosis was assessed by a
      non invasive method. In 2002, 6 patients had liver fibrosis assessment at
      hospital facilities, 4 patients were assessed with liver biopsy and 2 patients
      with Fibrotest-Actitest. 2 patients were treated for HCV at hospital. In 2003 and
      2004, 224 patients were assessed with Fibrotest-Actitest on site. Of these, 85
      were treated for HCV. SVR was achieved in 43%. We conclude that the combination
      of an onsite multidisciplinary team with the use of a noninvasive assessment
      method led to improved management of HCV infection in drug users' primary care
      facility.

PMID- 20811483
TI  - Expression and Localization of an Hsp70 Protein in the Microsporidian
      Encephalitozoon cuniculi.
AB  - Microsporidia spore surface proteins are an important, under investigated aspect
      of spore/host cell attachment and infection. For comparison analysis of surface
      proteins, we required an antibody control specific for an intracellular protein.
      An endoplasmic reticulum-associated heat shock protein 70 family member (Hsp70;
      ECU02_0100; "C1") was chosen for further analysis. DNA encoding the C1 hsp70 was
      amplified, cloned and used to heterologously express the C1 Hsp70 protein, and
      specific antiserum was generated. Two-dimensional Western blotting analysis
      showed that the purified antibodies were monospecific. Immunoelectron microscopy
      of developing and mature E. cuniculi spores revealed that the protein localized
      to internal structures and not to the spore surface. In spore adherence
      inhibition assays, the anti-C1 antibodies did not inhibit spore adherence to host
      cell surfaces, whereas antibodies to a known surface adhesin (EnP1) did so. In
      future studies, the antibodies to the 'C1' Hsp70 will be used to delineate spore
      surface protein expression.

PMID- 20811484
TI  - Death in 12-24-Year-Old Youth in Nova Scotia: High Risk of Preventable Deaths for
      Males, Socially Deprived and Rural Populations-A Report from the NSYOUTHS
      Program.
AB  - Deaths from avoidable causes represent the largest component of deaths in young
      people in Canada and have a considerable social cost in relation to years of
      potential life lost. We evaluated social and demographic determinants of deaths
      in youth aged 12-24 years in Nova Scotia for the period 1995-2004. Youth most at
      risk of death were males, the more socially deprived, and those living in rural
      areas. There was a five-fold increase in suicides and a three-fold increase in
      injury deaths in males compared to females and a substantial component of these
      deaths were amongst males living in rural areas. Initiatives and prevention
      policies should be targeted towards specific at-risk groups, particularly males
      living in rural areas. Published vital statistics hide these important trends and
      thus provide only limited evidence with which to base-prevention initiatives.

PMID- 20811485
TI  - Rhabdomyolysis-induced acute renal failure following fenofibrate therapy: a case
      report and literature review.
AB  - Fenofibrate, a fibric acid derivative, is used to treat diabetic dyslipidemia,
      hypertriglyceridemia, and combined hyperlipidemia, administered alone or in
      combination with statins. Rhabdomyolysis is defined as a pathological condition
      involving skeletal muscle cell damage leading to the release of toxic
      intracellular material into circulation. Its major causes include muscle
      compression or overexertion; trauma; ischemia; toxins; cocaine, alcohol, and drug
      use; metabolic disorders; infections. However, rhabdomyolysis associated with
      fenofibrate is extremely rare. Herein we report a 45-year-old female patient who
      was referred to our department because of generalized muscle pain, fatigue,
      weakness, and oliguria over the preceding 3 weeks. On the basis of the
      pathogenesis and clinical and laboratory examinations, a diagnosis of acute renal
      failure secondary to fenofibrate-induced rhabdomyolysis was made. Weekly
      followups for patients who are administered fenofibrate are the most important
      way to prevent possible complications.

PMID- 20811487
TI  - Delayed lead perforation: can we ever let the guard down?
AB  - Lead perforation is a major complication of cardiac rhythm management devices
      (CRMD), occurring in about 1%. While most lead perforations occur early, numerous
      instances of delayed lead perforation (occurring >30 days after implantation)
      have been reported in the last few years. Only about 40 such cases have been
      published, with the majority occurring <1 year after implantation. Herein, we
      describe the case of an 84-year-old female who presented with recurrent syncope
      and was diagnosed to have delayed pacemaker lead perforation 4.8 years after
      implantation. Through this report, we intend to highlight the increasing use of
      CRMD in elderly patients, and the lifelong risk of complications with these
      devices. Presentation can be atypical and a high index of suspicion is necessary
      for diagnosis.

PMID- 20811488
TI  - A case of double gallbladder with adenocarcinoma arising from the left hepatic
      duct: a case report and review of the literature.
AB  - Double gallbladder is a rare congenital biliary anomaly, but an accessory
      gallbladder arising from the left hepatic duct is a more remarkably rare
      congenital anomaly. We report a case of double gallbladder with adenocarcinoma
      and gallstones, which was preoperatively diagnosed by endoscopic retrograde
      cholangiopancreatography (ERCP) and then confirmed by open laparotomy. A review
      of the literature is presented.

PMID- 20811489
TI  - Prevalence, detection, and management of the metabolic syndrome in patients with
      acute myocardial infarction: role of an obesity-centric definition.
AB  - Background. We sought to determine and compare the prevalence of the Metabolic
      Syndrome (MS) in patients with acute myocardial infarction (AMI) utilizing the
      new International Diabetes Federation (IDF) definition with the older National
      Cholesterol Education Program (NCEP) definition. We also examined the clinical
      utility of MS in this context. Methods. A total of 107 consecutive patients with
      AMI were prospectively evaluated for MS. Fasting lipids obtained at admission and
      fasting glucose at discharge were used. A postdischarge folder audit verified
      rates of discharge coding and implementation of specific management strategies
      for MS. Results. Baseline patient characteristics included: mean age 59 +/- 13
      years; males 80%; diabetes 19%; mean BMI 29.7 +/- 8.4 kg/m(2). MS prevalence was
      54% by the IDF definition and 49% by the NCEP definition, with good agreement
      between definitions: kappa = 0.664, P < .001. Factors predictive of MS after
      multivariate analysis included: hypertension, fasting glucose, waist
      circumference, and serum HDL (all P < .05). Despite the high prevalence, MS was
      recognized at discharge in only 1 patient, and referral for exercise and/or
      weight-loss programs was undertaken in 5 patients. Conclusion. There is a high
      prevalence of MS utilizing contemporary definitions in patients with AMI: 54% by
      the IDF definition and 49% by NCEP criteria. Despite the high prevalence, MS was
      under-recognized and under-treated in this population.

PMID- 20811486
TI  - Review on Trypanosoma cruzi: Host Cell Interaction.
AB  - Trypanosoma cruzi, the causative agent of Chagas' disease, which affects a large
      number of individuals in Central and South America, is transmitted to vertebrate
      hosts by blood-sucking insects. This protozoan is an obligate intracellular
      parasite. The infective forms of the parasite are metacyclic and bloodstream
      trypomastigote and amastigote. Metacyclic trypomastigotes are released with the
      feces of the insect while amastigotes and bloodstream trypomastigotes are
      released from the infected host cells of the vertebrate host after a complex
      intracellular life cycle. The recognition between parasite and mammalian host
      cell involves numerous molecules present in both cell types. Here, we present a
      brief review of the interaction between Trypanosoma cruzi and its host cells,
      mainly emphasizing the mechanisms and molecules that participate in the T. cruzi
      invasion process of the mammalian cells.

PMID- 20811490
TI  - Template-directed ligation of tethered mononucleotides by t4 DNA ligase for
      kinase ribozyme selection.
AB  - BACKGROUND: In vitro selection of kinase ribozymes for small molecule
      metabolites, such as free nucleosides, will require partition systems that
      discriminate active from inactive RNA species. While nucleic acid catalysis of
      phosphoryl transfer is well established for phosphorylation of 5' or 2' OH of
      oligonucleotide substrates, phosphorylation of diffusible small molecules has not
      been demonstrated. METHODOLOGY/PRINCIPAL FINDINGS: This study demonstrates the
      ability of T4 DNA ligase to capture RNA strands in which a tethered
      monodeoxynucleoside has acquired a 5' phosphate. The ligation reaction therefore
      mimics the partition step of a selection for nucleoside kinase (deoxy)ribozymes.
      Ligation with tethered substrates was considerably slower than with nicked, fully
      duplex DNA, even though the deoxynucleotides at the ligation junction were Watson
      Crick base paired in the tethered substrate. Ligation increased markedly when the
      bridging template strand contained unpaired spacer nucleotides across from the
      flexible tether, according to the trends:
      A(2)>A(1)>A(3)>A(4)>A(0)>A(6)>A(8)>A(10) and T(2)>T(3)>T(4)>T(6) approximately
      T(1)>T(8)>T(10). Bridging T's generally gave higher yield of ligated product than
      bridging A's. ATP concentrations above 33 microM accumulated adenylated
      intermediate and decreased yields of the gap-sealed product, likely due to re
      adenylation of dissociated enzyme. Under optimized conditions, T4 DNA ligase
      efficiently (>90%) joined a correctly paired, or TratioG wobble-paired, substrate
      on the 3' side of the ligation junction while discriminating approximately 100
      fold against most mispaired substrates. Tethered dC and dG gave the highest
      ligation rates and yields, followed by tethered deoxyinosine (dI) and dT, with
      the slowest reactions for tethered dA. The same kinetic trends were observed in
      ligase-mediated capture in complex reaction mixtures with multiple substrates.
      The "universal" analog 5-nitroindole (dNI) did not support ligation when used as
      the tethered nucleotide. CONCLUSIONS/SIGNIFICANCE: Our results reveal a novel
      activity for T4 DNA ligase (template-directed ligation of a tethered
      mononucleotide) and establish this partition scheme as being suitable for the
      selection of ribozymes that phosphorylate mononucleoside substrates.

PMID- 20811492
TI  - Will cardiovascular disease prevention widen health inequalities?

PMID- 20811491
TI  - An intervention to reduce HIV risk behavior of substance-using men who have sex
      with men: a two-group randomized trial with a nonrandomized third group.
AB  - BACKGROUND: Substance use during sex is associated with sexual risk behavior
      among men who have sex with men (MSM), and MSM continue to be the group at
      highest risk for incident HIV in the United States. The objective of this study
      is to test the efficacy of a group-based, cognitive-behavioral intervention to
      reduce risk behavior of substance-using MSM, compared to a randomized attention
      control group and a nonrandomized standard HIV-testing group. METHODS AND
      FINDINGS: Participants (n = 1,686) were enrolled in Chicago, Los Angeles, New
      York City, and San Francisco and randomized to a cognitive-behavioral
      intervention or attention-control comparison. The nonrandomized group received
      standard HIV counseling and testing. Intervention group participants received six
      2-h group sessions focused on reducing substance use and sexual risk behavior.
      Attention-control group participants received six 2-h group sessions of videos
      and discussion of MSM community issues unrelated to substance use, sexual risk,
      and HIV/AIDS. All three groups received HIV counseling and testing at baseline.
      The sample reported high-risk behavior during the past 3 mo prior to their
      baseline visit: 67% reported unprotected anal sex, and 77% reported substance use
      during their most recent anal sex encounter with a nonprimary partner. The three
      groups significantly (p<0.05) reduced risk behavior (e.g., unprotected anal sex
      reduced by 32% at 12-mo follow-up), but were not different (p>0.05) from each
      other at 3-, 6-, and 12-mo follow-up. Outcomes for the 2-arm comparisons were not
      significantly different at 12-mo follow-up (e.g., unprotected anal sex, odds
      ratio = 1.14, confidence interval = 0.86-1.51), nor at earlier time points.
      Similar results were found for each outcome variable in both 2- and 3-arm
      comparisons. CONCLUSIONS: These results for reducing sexual risk behavior of
      substance-using MSM are consistent with results of intervention trials for other
      populations, which collectively suggest critical challenges for the field of HIV
      behavioral interventions. Several mechanisms may contribute to statistically
      indistinguishable reductions in risk outcomes by trial group. More explicit
      debate is needed in the behavioral intervention field about appropriate
      scientific designs and methods. As HIV prevention increasingly competes for
      behavior-change attention alongside other "chronic" diseases and mental health
      issues, new approaches may better resonate with at-risk groups. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00153361. Please see later in the article for
      the Editors' Summary.

PMID- 20811494
TI  - Structure of the altitude adapted hemoglobin of guinea pig in the R2-state.
AB  - BACKGROUND: Guinea pigs are considered to be genetically adapted to a high
      altitude environment based on the consistent finding of a high oxygen affinity of
      their blood. METHODOLOGY/PRINCIPAL FINDINGS: The crystal structure of guinea pig
      hemoglobin at 1.8 A resolution suggests that the increased oxygen affinity of
      guinea pig hemoglobin can be explained by two factors, namely a decreased
      stability of the T-state and an increased stability of the R2-state. The
      destabilization of the T-state can be related to the substitution of a highly
      conserved proline (P44) to histidine (H44) in the alpha-subunit, which causes a
      steric hindrance with H97 of the beta-subunit in the switch region. The
      stabilization of the R2-state is caused by two additional salt bridges at the
      beta1/beta2 interface. CONCLUSIONS/SIGNIFICANCE: Both factors together are
      supposed to serve to shift the equilibrium between the conformational states
      towards the high affinity relaxed states resulting in an increased oxygen
      affinity.

PMID- 20811493
TI  - Immunogenic profiling in mice of a HIV/AIDS vaccine candidate (MVA-B) expressing
      four HIV-1 antigens and potentiation by specific gene deletions.
AB  - BACKGROUND: The immune parameters of HIV/AIDS vaccine candidates that might be
      relevant in protection against HIV-1 infection are still undefined. The highly
      attenuated poxvirus strain MVA is one of the most promising vectors to be use as
      HIV-1 vaccine. We have previously described a recombinant MVA expressing HIV-1
      Env, Gag, Pol and Nef antigens from clade B (referred as MVA-B), that induced HIV
      1-specific immune responses in different animal models and gene signatures in
      human dendritic cells (DCs) with immunoregulatory function. METHODOLOGY/PRINCIPAL
      FINDINGS: In an effort to characterize in more detail the immunogenic profile of
      MVA-B and to improve its immunogenicity we have generated a new vector lacking
      two genes (A41L and B16R), known to counteract host immune responses by blocking
      the action of CC-chemokines and of interleukin 1beta, respectively (referred as
      MVA-B DeltaA41L/DeltaB16R). A DNA prime/MVA boost immunization protocol was used
      to compare the adaptive and memory HIV-1 specific immune responses induced in
      mice by the parental MVA-B and by the double deletion mutant MVA-B
      DeltaA41L/DeltaB16R. Flow cytometry analysis revealed that both vectors triggered
      HIV-1-specific CD4(+) and CD8(+) T cells, with the CD8(+) T-cell compartment
      responsible for >91.9% of the total HIV-1 responses in both immunization groups.
      However, MVA-B DeltaA41L/DeltaB16R enhanced the magnitude and polyfunctionality
      of the HIV-1-specific CD4(+) and CD8(+) T-cell immune responses. HIV-1-specific
      CD4(+) T-cell responses were polyfunctional and preferentially Env-specific in
      both immunization groups. Significantly, while MVA-B induced preferentially Env
      specific CD8(+) T-cell responses, MVA-B DeltaA41L/DeltaB16R induced more GPN
      specific CD8(+) T-cell responses, with an enhanced polyfunctional pattern. Both
      vectors were capable of producing similar levels of antibodies against Env.
      CONCLUSIONS/SIGNIFICANCE: These findings revealed that MVA-B and MVA-B
      DeltaA41L/DeltaB16R induced in mice robust, polyfunctional and durable T-cell
      responses to HIV-1 antigens, but the double deletion mutant showed enhanced
      magnitude and quality of HIV-1 adaptive and memory responses. Our observations
      are relevant in the immune evaluation of MVA-B and on improvements of MVA vectors
      as HIV-1 vaccines.

PMID- 20811495
TI  - Harnessing health IT for improved cardiovascular risk management.

PMID- 20811496
TI  - Production of TNF-alpha, IL-12(p40) and IL-17 can discriminate between active TB
      disease and latent infection in a West African cohort.
AB  - BACKGROUND: Mycobacterium tuberculosis (MTb) infects approximately 2 billion
      people world-wide resulting in almost 2 million deaths per year. Determining
      biomarkers that distinguish different stages of tuberculosis (TB) infection and
      disease will provide tools for more effective diagnosis and ultimately aid in the
      development of new vaccine candidates. The current diagnostic kits utilising
      production of IFN-gamma in response to TB antigens can detect MTb infection but
      are unable to distinguish between infection and disease. The aim of this study
      was to assess if the use of a longer term assay and the analysis of multiple
      cytokines would enhance diagnosis of active TB in a TB-endemic population.
      METHODS: We compared production of multiple cytokines (TNF-alpha, IFN-gamma, IL
      10, IL-12(p40), IL-13, IL-17 and IL-18) following long-term (7 days) stimulation
      of whole-blood with TB antigens (ESAT-6/CFP-10 (EC), PPD or TB10.4) from TB cases
      (n = 36) and their Mycobacterium-infected (TST+; n = 20) or uninfected (TST-; n =
      19) household contacts (HHC). RESULTS AND CONCLUSIONS: We found that TNF-alpha
      production following EC stimulation and TNF-alpha and IL-12(p40) following TB10.4
      stimulation were significantly higher from TB cases compared to TST+ HHC, while
      production of IFN-gamma and IL-13 were significantly higher from TST+ compared to
      TST- HHC following PPD or EC stimulation. Combined analysis of TNF-alpha, IL
      12(p40) and IL-17 following TB10.4 stimulation resulted in 85% correct
      classification into TB cases or TST+ HHC. 74% correct classification into TST+ or
      TST- HHC was achieved with IFN-gamma alone following TB10.4 stimulation (69%
      following EC) and little enhancement was seen with additional cytokines. We also
      saw a tendency for TB cases infected with M. africanum to have increased TNF
      alpha and IL-10 production compared to those infected with M. tuberculosis. Our
      results provide further insight into the pathogenesis of tuberculosis and may
      enhance the specificity of the currently available diagnostic tests, particularly
      for diagnosis of active TB.

PMID- 20811497
TI  - Zinc(II) and Nickel(II) Benzoate Complexes from the Use of 1-methyl-4,5
      diphenylimidazole.
AB  - Two new complexes, [Zn(O(2)CPh)(2)(L)(2)].2MeOH (1.2MeOH) and
      [Ni(2)(O(2)CPh))(4)(L)(2)].2MeCN (2.2MeCN), have been synthesized and
      characterized by X-ray analysis in the course of an ongoing investigation of the
      M(II)/X(-)/L [M(II) = Co, Ni, Cu, Zn; X(-) = Cl(-), Br(-), I(-), NCS(-), NO(3) (
      ), N(3) (-), PhCO(2) (-); L = 1-methyl-4,5-diphenylimidazole] reaction system,
      aiming at understanding and assessing the relative strength and the way in which
      the intermolecular interactions control the supramolecular organization of these
      compounds. In the mononuclear complex 1.2MeOH, the benzoate ion acts as a
      monodentate ligand resulting in a distorted tetrahedral N(2)O(2) coordination
      environment. Complex 2.2MeCN exhibits a dinuclear paddle-wheel structure; each
      Ni(II) has a square pyramidal NiNO(4) chromophore with four benzoate oxygens in
      the basal plane and the pyridine-type nitrogen atom of one ligand L at the apex.
      The structure of 1.2MeOH is stabilized by intramolecular pi-pi interactions
      between aromatic rings of adjacent 4,5-diphenylimidazole moieties; it is a
      feature also evidenced in similar compounds of the type [MX(2)L(2)].

PMID- 20811498
TI  - Polymeric-calcium phosphate cement composites-material properties: in vitro and
      in vivo investigations.
AB  - New polymeric calcium phosphate cement composites (CPCs) were developed. Cement
      powder consisting of 60 wt% tetracalcium phosphate, 30 wt% dicalcium phosphate
      dihydrate, and 10 wt% tricalcium phosphate was combined with either 35% w/w poly
      methyl vinyl ether maleic acid or polyacrylic acid to obtain CPC-1 and CPC-2. The
      setting time and compressive and diametral tensile strength of the CPCs were
      evaluated and compared with that of a commercial hydroxyapatite cement. In vitro
      cytotoxicity and in vivo biocompatibility of the two CPCs and hydroxyapatite
      cement were assessed. The setting time of the cements was 5-15 min. CPC-1 and CPC
      2 showed significantly higher compressive and diametral strength values compared
      to hydroxyapatite cement. CPC-1 and CPC-2 were equivalent to Teflon controls
      after 1 week. CPC-1, CPC-2, and hydroxyapatite cement elicited a moderate to
      intense inflammatory reaction at 7 days which decreased over time. CPC-1 and CPC
      2 show promise for orthopedic applications.

PMID- 20811499
TI  - Adjusting HIV prevalence for survey non-response using mortality rates: an
      application of the method using surveillance data from Rural South Africa.
AB  - BACKGROUND: The main source of HIV prevalence estimates are household and
      population-based surveys; however, high refusal rates may hinder the
      interpretation of such estimates. The study objective was to evaluate whether
      population HIV prevalence estimates can be adjusted for survey non-response using
      mortality rates. METHODOLOGY/PRINCIPAL FINDINGS: Data come from the longitudinal
      Africa Centre Demographic Information System (ACDIS), in rural South Africa.
      Mortality rates for persons tested and not tested in the 2005 HIV surveillance
      were available from routine household surveillance. Assuming HIV status among
      individuals contacted but who refused to test (non-response) is missing at random
      and mortality among non-testers can be related to mortality of those tested a
      mathematical model was developed. Non-parametric bootstrapping was used to
      estimate the 95% confidence intervals around the estimates. Mortality rates were
      higher among untested (16.9 per thousand person-years) than tested population
      (11.6 per thousand person-years), suggesting higher HIV prevalence in the former.
      Adjusted HIV prevalence for females (15-49 years) was 31.6% (95% CI 26.1-37.1)
      compared to observed 25.2% (95% CI 24.0-26.4). For males (15-49 years) adjusted
      HIV prevalence was 19.8% (95% CI 14.8-24.8), compared to observed 13.2% (95% CI
      12.1-14.3). For both sexes (15-49 years) combined, adjusted prevalence was 27.5%
      (95% CI 23.6-31.3), and observed prevalence was 19.7% (95% CI 19.6-21.3).
      Overall, observed prevalence underestimates the adjusted prevalence by around 7
      percentage points (37% relative difference). CONCLUSIONS/SIGNIFICANCE: We
      developed a simple approach to adjust HIV prevalence estimates for survey non
      response. The approach has three features that make it easy to implement and
      effective in adjusting for selection bias than other approaches. Further research
      is needed to assess this approach in populations with widely available HIV
      treatment (ART).

PMID- 20811501
TI  - Anticipating knowledge to inform species management: predicting spatially
      explicit habitat suitability of a colonial vulture spreading its range.
AB  - BACKGROUND: The knowledge of both potential distribution and habitat suitability
      is fundamental in spreading species to inform in advance management and
      conservation planning. After a severe decline in the past decades, the griffon
      vulture (Gyps fulvus) is now spreading its breeding range towards the northwest
      in Spain and Europe. Because of its key ecological function, anticipated spatial
      knowledge is required to inform appropriately both vulture and ecosystem
      management. METHODOLOGY/FINDINGS: Here we used maximum entropy (Maxent) models to
      determine the habitat suitability of potential and current breeding distribution
      of the griffon vulture using presence-only data (N = 124 colonies) in north
      western Spain. The most relevant ecological factors shaping this habitat
      suitability were also identified. The resulting model had a high predictive
      performance and was able to predict species' historical distribution. 7.5%
      (approximately 1,850 km(2)) of the study area resulted to be suitable breeding
      habitat, most of which (approximately 70%) is already occupied by the species.
      Cliff availability and livestock density, especially of sheep and goats, around
      10 km of the colonies were the fundamental factors determining breeding habitat
      suitability for this species. CONCLUSIONS/SIGNIFICANCE: Griffon vultures could
      still spread 50-60 km towards the west, increasing their breeding range in 1,782
      km(2). According to our results, 7.22% of the area suitable for griffon vulture
      will be affected by wind farms, so our results could help to better plan wind
      farm locations. The approach here developed could be useful to inform management
      of reintroductions and recovery programmes currently being implemented for both
      the griffon vulture and other threatened vulture species.

PMID- 20811500
TI  - Expression of stretch-activated two-pore potassium channels in human myometrium
      in pregnancy and labor.
AB  - BACKGROUND: We tested the hypothesis that the stretch-activated, four
      transmembrane domain, two pore potassium channels (K2P), TREK-1 and TRAAK are
      gestationally-regulated in human myometrium and contribute to uterine relaxation
      during pregnancy until labor. METHODOLOGY: We determined the gene and protein
      expression of K2P channels in non-pregnant, pregnant term and preterm laboring
      myometrium. We employed both molecular biological and functional studies of K2P
      channels in myometrial samples taken from women undergoing cesarean delivery of a
      fetus. PRINCIPAL FINDINGS: TREK-1, but not TREK-2, channels are expressed in
      human myometrium and significantly up-regulated during pregnancy. Down-regulation
      of TREK-1 message was seen by Q-PCR in laboring tissues consistent with a role
      for TREK-1 in maintaining uterine quiescence prior to labor. The TRAAK channel
      was unregulated in the same women. Blockade of stretch-activated channels with a
      channel non-specific tarantula toxin (GsMTx-4) or the more specific TREK-1
      antagonist L-methionine ethyl ester altered contractile frequency in a dose
      dependent manner in pregnant myometrium. Arachidonic acid treatment lowered
      contractile tension an effect blocked by fluphenazine. Functional studies are
      consistent with a role for TREK-1 in uterine quiescence. CONCLUSIONS: We provide
      evidence supporting a role for TREK-1 in contributing to uterine quiescence
      during gestation and hypothesize that dysregulation of this mechanism may
      underlie certain cases of spontaneous pre-term birth.

PMID- 20811502
TI  - Monitoring temporal changes in the specificity of an oral HIV test: a novel
      application for use in postmarketing surveillance.
AB  - BACKGROUND: Postmarketing surveillance is routinely conducted to monitor
      performance of pharmaceuticals and testing devices in the marketplace. However,
      these surveillance methods are often done retrospectively and, as a result, are
      not designed to detect issues with performance in real-time. METHODS AND
      FINDINGS: Using HIV antibody screening test data from New York City STD clinics,
      we developed a formal, statistical method of prospectively detecting temporal
      clusters of poor performance of a screening test. From 2005 to 2008, New York
      City, as well as other states, observed unexpectedly high false-positive (FP)
      rates in an oral fluid-based rapid test used for screening HIV. We attempted to
      formally assess whether the performance of this HIV screening test statistically
      deviated from both local expectation and the manufacturer's claim for the test.
      Results indicate that there were two significant temporal clusters in the FP rate
      of the oral HIV test, both of which exceeded the manufacturer's upper limit of
      the 95% CI for the product. Furthermore, the FP rate of the test varied
      significantly by both STD clinic and test lot, though not by test operator.
      CONCLUSIONS: Continuous monitoring of surveillance data has the benefit of
      providing information regarding test performance, and if conducted in real-time,
      it can enable programs to examine reasons for poor test performance in close
      proximity to the occurrence. Techniques used in this study could be a valuable
      addition for postmarketing surveillance of test performance and may become
      particularly important with the increase in rapid testing methods.

PMID- 20811504
TI  - A herpes simplex viral vector expressing green fluorescent protein can be used to
      visualize morphological changes in high-density neuronal culture.
AB  - High-density cultures of mammalian neurons offer a model system for studies of
      brain development, but the morphological features of individual neurons is
      difficult to ascertain. We show that a herpes virus vector expressing a
      bioluminescent protein allows detailed morphometric analyses of living neurons in
      complex culture environments. Expression of enhanced green fluorescent protein
      (eGFP) was constitutively driven in neurons using the herpes simplex virus
      amplicon system. This system allowed us to make novel observations regarding
      development in high-density cultures from rat hippocampus and cerebellum. After
      the phase of initial neurite outgrowth, maturing neurons continue to show rapid
      remodeling of the neurite branches (0.79 +/- 0.11 mum/h per neurite; mean +/-
      SEM, n=8), and displacement of the soma within the neurite arbor (1.35 +/- 0.74
      mum/h). These results demonstrate that a substantial capacity for morphological
      plasticity persists in maturing mammalian CNS neurons after cessation of net
      neurite outgrowth in early development.

PMID- 20811503
TI  - Beta-catenin signaling negatively regulates intermediate progenitor population
      numbers in the developing cortex.
AB  - Intermediate progenitor cells constitute a second proliferative cell type in the
      developing mammalian cerebral cortex. Little is known about the factors that
      govern the production of intermediate progenitors. Although persistent expression
      of stabilized beta-catenin was found to delay the maturation of radial glial
      progenitors into intermediate progenitors, the relationship between beta-catenin
      signaling and intermediate progenitors remains poorly understood. Using a
      transgenic reporter mouse for Axin2, a direct target of Wnt/beta-catenin
      signaling, we observed that beta-catenin signaling is decreased in intermediate
      progenitor cells relative to radial glial progenitors. Conditional deletion of
      beta-catenin from mouse cortical neural progenitors increased intermediate
      progenitor numbers, while conditional expression of stabilized beta-catenin
      reduced the intermediate progenitor population. Together, these findings provide
      evidence that beta-catenin signaling in radial progenitors negatively regulates
      intermediate progenitor cell number during cortical development.

PMID- 20811505
TI  - T2* magnetic resonance imaging sequences reflect brain tissue iron deposition
      following intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: To examine the utility of magnetic resonance imaging
      (MRI) T2* sequences as a measure of iron overload in the brain following
      intracerebral hemorrhage (ICH). METHODS: We examined the time course of T2*
      changes in the brain around intracerebral hemorrhages in a series of patients. We
      also performed a series of experiments in an animal model of ICH, examining the
      time course of T2* changes along with correlation of these changes with
      histological markers of ferric iron deposition. RESULTS: We found that T2*
      changes in the brain occur with increasing intensity and spatial distribution
      over a three month period. Experimental ICH in the rat model induces similar
      changes, and these changes correlate tightly with histological markers of ferric
      iron deposition. CONCLUSIONS: MRI T2* changes after ICH can be used to measure
      the degree of iron overload in the brain. The T2* sequence may be useful as a
      measure of interventions aimed at reducing ICH-related brain injury by reducing
      iron deposition.

PMID- 20811506
TI  - A Postnatal Pax7 Progenitor Gives Rise to Pituitary Adenomas.
AB  - Pituitary adenomas are classified into functioning and nonfunctioning (silent)
      tumors on the basis of hormone secretion. However, the mechanism of tumorigenesis
      and the cell of origin for pituitary adenoma subtypes remain to be elucidated.
      Employing a tamoxifen-inducible mouse model, we demonstrate that a novel
      postnatal Pax7(+) progenitor cell population in the pituitary gland gives rise to
      silent corticotroph macro-adenomas when the retinoblastoma tumor suppressor is
      conditionally deleted. While Pax transcriptional factors are critical for
      embryonic patterning as well as postnatal stem cell renewal for many organs, we
      have discovered that Pax7 marks a restricted cell population in the postnatal
      pituitary intermediate lobe. This Pax7(+) early progenitor cell population is
      overlapping but ontologically downstream of the Nestin(+) pituitary stem cell
      population, yet upstream of another newly discovered Myf6(+) late progenitor cell
      population. Interestingly, the Pax7(+) progenitor cell population is
      evolutionarily conserved in primates and humans, and Pax7 expression is
      maintained not only in murine tumors but also in human functioning and silent
      corticotropinomas. Taken together, our results strongly suggest that human silent
      corticotroph adenomas may in fact arise from a Pax7 lineage of the intermediate
      lobe, a region of the human pituitary bearing closer scientific interest as a
      reservoir of pituitary progenitor cells.

PMID- 20811507
TI  - The Process of Delivering Peer-Based Alcohol Intervention Programs in College
      Settings.

PMID- 20811508
TI  - Thinking About Development: The Value of Animal-Based Research for the Study of
      Human Development.
AB  - Gottlieb promoted the value of a developmental psychobiological systems approach
      to the study of human development. This approach recognizes the importance of
      comparative, animal-based research to advancing our understanding of the
      complexities and dynamics of the process of development. The major contribution
      of animal developmental studies is their provision of food for thought
      (hypotheses, not facts) about human development and general principles of
      development. Here we briefly describe how, guided by Gottlieb's pioneering
      vision, we have utilized coordinated studies of non-human animal and human
      infants to begin to identify patterns of selective attention and perceptual
      processing that are common across species in early development. Our converging
      findings highlight the importance of multimodal (intersensory) redundancy in
      guiding and constraining early perceptual learning in avian and mammalian
      species.

PMID- 20811509
TI  - Early Claiming of Social Security Benefits and Labor Supply Behavior of Older
      Americans.
AB  - The labor supply incentives provided by the early retirement rules of the United
      States Social Security Old Age benefits program are of growing importance as the
      Normal Retirement Age (NRA) increases to 67, and the labor force participation of
      Older Americans starts to increase. These incentives allow individuals who claim
      benefits before the NRA but continue to work, or return to the labor force, to
      increase their future rate of benefit pay by having benefits withheld. Since the
      adjustment of the benefit rate takes place only after the NRA is reached,
      benefits received before the NRA can become actuarially unfair for those who
      continue to work after claiming. Consistent with these incentives, estimates from
      bivariate models of the monthly labor force exit and claiming hazards using data
      from the Health and Retirement Study indicate that early claimers who do not
      withdraw from the labor force around the time they claim are increasingly likely
      to stay in the labor force.

PMID- 20811510
TI  - A framework for feature selection in clustering.
AB  - We consider the problem of clustering observations using a potentially large set
      of features. One might expect that the true underlying clusters present in the
      data differ only with respect to a small fraction of the features, and will be
      missed if one clusters the observations using the full set of features. We
      propose a novel framework for sparse clustering, in which one clusters the
      observations using an adaptively chosen subset of the features. The method uses a
      lasso-type penalty to select the features. We use this framework to develop
      simple methods for sparse K-means and sparse hierarchical clustering. A single
      criterion governs both the selection of the features and the resulting clusters.
      These approaches are demonstrated on simulated data and on genomic data sets.

PMID- 20811511
TI  - Support for Students Exposed to Trauma: A Pilot Study.
AB  - With high rates of trauma exposure among students, the need for intervention
      programs is clear. Delivery of such programs in the school setting eliminates key
      barriers to access, but there are few programs that demonstrate efficacy in this
      setting. Programs to date have been designed for delivery by clinicians, who are
      a scarce resource in many schools. This study describes preliminary feasibility
      and acceptability data from a pilot study of a new program, Support for Students
      Exposed to Trauma, adapted from the Cognitive Behavioral Intervention for Trauma
      in Schools (CBITS) program. Because of its "pilot" nature, all results from the
      study should be viewed as preliminary. Results show that the program can be
      implemented successfully by teachers and school counselors, with good
      satisfaction among students and parents. Pilot data show small reductions in
      symptoms among the students in the SSET program, suggesting that this program
      shows promise that warrants a full evaluation of effectiveness.

PMID- 20811512
TI  - Interdisciplinary approaches to calcium dynamics and secretory processes in
      cells.

PMID- 20811513
TI  - Mechanisms of short-term plasticity at neuromuscular active zones of Drosophila.
AB  - DURING SHORT BURSTS OF NEURONAL ACTIVITY, CHANGES IN THE EFFICACY OF
      NEUROTRANSMITTER RELEASE ARE GOVERNED PRIMARILY BY TWO COUNTERACTING PROCESSES:
      (1) Ca(2+)-dependent elevations of vesicle release probability and (2) depletion
      of synaptic vesicles. The dynamic interplay of both processes contributes to the
      expression of activity-dependent synaptic plasticity. Here, we exploited various
      facets of short-term plasticity at the Drosophila neuromuscular junction to
      dissect these two processes. This enabled us to rigorously analyze different
      models of synaptic vesicle pools in terms of their size and mobilization
      properties. Independent of the specific model, we estimate approximately 300
      readily releasable vesicles with an average release probability of approximately
      50% in 1 mM extracellular calcium ( approximately 5% in 0.4 mM extracellular
      calcium) under resting conditions. The models also helped interpreting the
      altered short-term plasticity of the previously reported mutant of the active
      zone component Bruchpilot (BRP). Finally, our results were independently
      confirmed through fluctuation analysis. Our data reveal that the altered short
      term plasticity observed in BRP mutants cannot be accounted for by delocalized
      Ca(2+) channels alone and thus suggest an additional role of BRP in short-term
      plasticity.

PMID- 20811514
TI  - Thermal windows on Brazilian free-tailed bats facilitate thermoregulation during
      prolonged flight.
AB  - The Brazilian free-tailed bat (Tadarida brasiliensis) experiences challenging
      thermal conditions while roosting in hot caves, flying during warm daylight
      conditions, and foraging at cool high altitudes. Using thermal infrared cameras,
      we identified hot spots along the flanks of free-ranging Brazilian free-tailed
      bats, ventral to the extended wings. These hot spots are absent in syntopic cave
      myotis (Myotis velifer), a species that forages over relatively short distances,
      and does not engage in long-distance migration. We hypothesized that the hot
      spots, or "radiators," on Brazilian free-tailed bats may be adaptations for
      migration, particularly in this long-distance, high-flying species. We examined
      the vasculature of radiators on Brazilian free-tailed bats with transillumination
      to characterize the unique arrangements of arteries and veins that are positioned
      perpendicular to the body in the proximal region of the wing. We hypothesized
      that these radiators aid in maintaining heat balance by flushing the uninsulated
      thermal window with warm blood, thereby dissipating heat while bats are flying
      under warm conditions, but shunting blood away and conserving heat when they are
      flying in cooler air at high altitudes. We also examined fluid-preserved
      specimens representing 122 species from 15 of 18 chiropteran families and
      radiators appeared present only in species in the family Molossidae, including
      both sedentary and migratory species and subspecies. Thus, the radiator appears
      to be a unique trait that may facilitate energy balance and water balance during
      sustained dispersal, foraging, and long-distance migration.

PMID- 20811515
TI  - Integrating meteorology into research on migration.
AB  - Atmospheric dynamics strongly influence the migration of flying organisms. They
      affect, among others, the onset, duration and cost of migration, migratory
      routes, stop-over decisions, and flight speeds en-route. Animals move through a
      heterogeneous environment and have to react to atmospheric dynamics at different
      spatial and temporal scales. Integrating meteorology into research on migration
      is not only challenging but it is also important, especially when trying to
      understand the variability of the various aspects of migratory behavior observed
      in nature. In this article, we give an overview of some different modeling
      approaches and we show how these have been incorporated into migration research.
      We provide a more detailed description of the development and application of two
      dynamic, individual-based models, one for waders and one for soaring migrants, as
      examples of how and why to integrate meteorology into research on migration. We
      use these models to help understand underlying mechanisms of individual response
      to atmospheric conditions en-route and to explain emergent patterns. This type of
      models can be used to study the impact of variability in atmospheric dynamics on
      migration along a migratory trajectory, between seasons and between years. We
      conclude by providing some basic guidelines to help researchers towards finding
      the right modeling approach and the meteorological data needed to integrate
      meteorology into their own research.

PMID- 20811518
TI  - Calcium, inorganic phosphates, alkaline and acid phosphatase activities in breast
      cancer patients in Calabar, Nigeria.
AB  - BACKGROUND: Breast cancer is the commonest malignancy of women in Nigeria. Change
      in serum levels of some biochemical parameters could assist diagnosis and follow
      up of breast cancer. OBJECTIVE: To determine serum levels of calcium, inorganic
      phosphates, alkaline phosphatase (ALP) and acid phosphatase (ACP) activities in
      patients with breast cancer, and change in the serum levels over time. METHODS:
      Total serum calcium and inorganic phosphates, and serum ALP and ACP activities
      were determined in 25 women with breast cancer and 25 age-matched controls using
      colorimetric and enzymatic methods, over 6 months with bimonthly analysis.
      RESULTS: The serum calcium level, ALP and ACP activities were significantly
      higher (p<0.05) in the study group than in the control group. No significant
      difference was seen in the inorganic phosphate levels of both groups. There were
      significant increases in serum calcium levels, ALP and ACP activities in the
      study group with time (p<0.05), whereas no significant increase was observed in
      the control group. CONCLUSION: Breast cancer patients have higher calcium levels
      and higher ALP and ACP activities. The increase in the levels of these parameters
      with time shows that they could be of importance in monitoring treatment and
      disease progress in a resource-poor setting.

PMID- 20811517
TI  - Trace elements and vitamin E status in Nigerian patients with prostate cancer.
AB  - BACKGROUND: Prostate cancer is the most common type of cancer among men.
      OBJECTIVES: To investigate the trace elements (Se, Zn, Cu and Cd) and vitamin E
      status of some Nigerian prostate cancer (PCa) patients relative to their prostate
      specific antigen (PSA) values. METHODS: Prostate cancer patients were assigned
      into groups 1, 2 and 3 with PSA of 5-10 ng/ml, 11-20 ng/ml and > 20 ng/ml,
      respectively. RESULTS: The results showed that the levels of whole blood
      superoxide dismutase (SOD) and serum Se and Zn were significantly lower (p< 0.05)
      in the PCa patients. Specifically, levels of SOD, Se and Zn decreased by 67%, 30%
      and 35%; 70%, 52% and 41%; 81%, 58% and 47%, in subjects with PSA of 5-10 ng/ml,
      11-20 ng/ml and > 20 ng/ml, respectively. There were no significant differences
      (p> 0.05) in levels of Cu and Cd. Serum Cu/ Zn ratio were significantly higher in
      PCa patients. The Cu/ Zn ratios were 1: 1.2: 1.3 for subjects in groups 1, 2 and
      3, respectively. Vitamin E levels in PCa patients were significantly lower and
      followed the order; normal > PSA (5-10) > PSA (11-20) > PSA (> 20). CONCLUSIONS:
      Deficiency of vitamin E, Zn and Se may be risk factors for development of PCa.

PMID- 20811519
TI  - Testicular and para-testicular tumors in south western Nigeria.
AB  - BACKGROUND: Tumors of the testis and paratesticular tissues are rare, especially
      in men of African descent. In recent reviews however, the incidence is rising
      among the Caucasians and black Americans. We set out to determine the incidence
      in South-Western Nigeria and to examine the histopathologic variants. METHODS: A
      retrospective study of patients who had histopathologically confirmed testicular
      and para-testicular tumours between 1989 and 2005 (17 years). Their records were
      documented at the Ife-Ijesha cancer registry which serves 4.7 million men
      residing in three states of South-Western Nigeria. RESULTS: There were 26 cases
      of testicular and para-testicular tumors with an average incidence of 1.5 cases
      per year. The incidence of testicular cancer in our study was 0.55 per 100,000
      population (95% CI, 0.52-0.57) and accounted for 1.1% of all male cancers.
      Rhabdomyosarcomas were the most common variety (70% of the paratesticular tumors
      and 26.8% of all tumors of the testis). Seminomas comprised 50% of the germ cell
      tumors and 15.4% of all testicular tumors in this series. CONCLUSION: There still
      remains a low incidence of testis cancer in the South Western Nigeria. The
      reduction in the incidence of seminomas makes rhabdomyosarcomas the most
      predominant tumor in South Western Nigeria.

PMID- 20811520
TI  - Blood loss and contributing factors in femoral fracture surgery.
AB  - BACKGROUND: Substantial blood losses frequently accompany orthopedic procedures.
      METHODS: We prospectively noted peri-operative hemoglobin changes in 93 patients
      undergoing surgery for femoral fracture with an aim of establishing blood loss
      and related factors. RESULTS: The mean total blood loss assessed 72 hours after
      the surgical procedure was 3.31 (SD 1.56) units of whole blood. A multiple
      regression analysis revealed diathermy use and a simple fracture pattern as
      significant factors in reducing blood loss (p<0.01). CONCLUSIONS: Open
      intramedullary fixation of femur fractures leads to considerable peri-operative
      blood loss. This is can be reduced by use of diathermy during surgery.

PMID- 20811521
TI  - Prevalence and risk factors of low back pain among nurses in a typical Nigerian
      hospital.
AB  - OBJECTIVE: The objective of this study was to determine the prevalence and risk
      factors of LBP among nurses in a typical Nigerian Specialist Hospital. METHODS: A
      cross-sectional study was designed to determine the prevalence and risk factors
      for LBP among nurses in a typical Nigerian Hospital. A department-to-department
      enquiry was conducted using a self structured valid and reliable questionnaire.
      RESULT: Four hundred and eight respondents (148 [36.27%] males and 260 [63.73%]
      females) participated in the study. The 12 month prevalence of LBP was 300
      (73.53%). LBP was more prevalent among female nurses (68%) than the male nurses
      (32%). It was also associated with occupational hazard and poor knowledge of back
      care ergonomics. The prevalence of LBP in MMSH is comparable to levels recorded
      abroad. However, in this study LBP did not feature as a major cause of sickness
      absence in the work place CONCLUSION: It was concluded that poor back care
      ergonomics is the major predisposing factor of LBP.

PMID- 20811522
TI  - Antenatal determinants of oro-facial clefts in Southern Nigeria.
AB  - OBJECTIVES: Cleft lip with or without cleft palate, is the most common serious
      congenital anomaly that affects the orofacial regions. The management and care of
      the cleft patient constitutes a substantial proportion of the workload of the
      Nigerian maxillofacial surgeon and allied specialties. Yet, there are no specific
      programmes targeted at this group. We believe that the findings of this study is
      capable of identifying useful interventions for designing programs that will lead
      to a reduction in the burden of orofacial cleft in Nigeria. METHODS: It was a
      transverse cross-sectional study that was undertaken at the Maxillofacial Units
      of the University of Benin Teaching Hospital and the Central Hospital, Benin City
      respectively. The prevalence and antenatal determinants of cleft lip and palate
      were determined. RESULTS: Cleft lip and palate were often encountered in clinical
      practice in Benin City with a prevalence of 1.35%. The results showed that
      orofacial clefts were commoner in females and that the combined unilateral cleft
      lip and palate was the commonest entity encountered amongst the cases. The
      following risk factors were associated with the risk of development of cleft lip
      and palate: Paternal age >40 years, maternal age >35 years, genetic/family
      history, low socio-economic status, alcohol consumption and indulgence in the
      intake of herbal medications in pregnancy. CONCLUSION: Public health education
      programmes and advocacy activities geared towards raising awareness of the
      identified risk factors for the development of cleft lip and or cleft palate
      would go a long way to obviate the occurrence and reduce the burden.

PMID- 20811523
TI  - Overweight and obesity among patients attending a Nigerian oral surgery clinic:
      implications for oral surgical practice in Nigeria.
AB  - AIM: To determine the prevalence of overweight and obesity among patients
      attending oral and maxillofacial outpatient clinic of the Lagos University
      Teaching Hospital, Nigeria; and discuss the clinical and surgical implications
      that obesity has on the delivery of oral and maxillofacial surgical and
      anaesthetic care. METHODS: Consecutive patients presenting to the oral and
      maxillofacial surgery outpatient clinic at the Lagos University Teaching
      Hospital, Nigeria over a 4-month period (May-August 2004) were screened for age,
      sex, height and weight. All of the patients were treated for dentoalveolar
      surgical procedures (routine and surgical extractions), incisional and excisional
      biopsies, and enucleation under local anaesthesia. RESULTS: The BMIs of the
      studied patients ranged from 16.7 to 39.8 kg/m(2), with a mean of 24.6 +/- 4.5
      kg/m(2). Prevalence of excess weight was 39.1%. Thirty-one (11.4%) patients were
      obese and 75 (27.7%) patients were overweight. A significant difference was
      observed in the BMIs of male and female patients (P=0.000). The age groups < 30
      years had mean BMIs that were considered normal; whereas other age groups above
      30 years had mean BMIs that were considered overweight. Prevalence of obesity
      increases with increasing age. Obese individuals were seen in all the age groups
      except those < 20 years. CONCLUSIONS: The prevalence of excess weight (overweight
      and obesity) in patients presenting in the studied oral and maxillofacial
      outpatient setting was 39.1%. Oral and maxillofacial surgeon needs to be aware of
      obesity-/overweight-related medical and surgical issues and take them into
      consideration when treating these patients.

PMID- 20811524
TI  - Waiting time for emergency abdominal surgery in Zaria, Nigeria.
AB  - BACKGROUND: Management of surgical emergencies in Nigeria is characterised by
      mismatch between supply of facilities and demand for care. This study aimed to
      evaluate the waiting time between presentation at hospital with acute abdominal
      disease and operative intervention. PATIENTS AND METHOD: We prospectively studied
      adult patients with abdominal diseases requiring emergency operation. The
      interval between presentation and first contact with emergency room doctors was
      defined as T1; time from contact to decision to operate as T2; time taken to
      resuscitate patient T3 and to commencement of operation T4. Causes of delay and
      its impact on outcome of treatment were noted. RESULTS: There were 488 patients,
      mean age 32 +/-1.7 SD years. TT ranged between 0.8 and 79.0 hours, mean 22.3 +/-
      10.0 hours. In 81.6% operative intervention was delayed beyond 6 hours of which
      financial constraints accounted for 53.8%. T3 accounted for the longest delay
      (0.5 -53.0 hours). Patients of lower socio-economic class had longer T3
      (p<0.005). Waiting for complementary investigations caused delay in 22.1%. Post
      operative complications (p=0.0001) and their severity were higher in patients
      with longer TT. Prolonged TT (p<0.001), ASA grade (0.005) and time from onset of
      symptoms to admission (p=0.009) were associated with mortality. Patients whose
      operations were delayed beyond 24 hours had a longer hospital stay. CONCLUSION:
      Emergency abdominal operations were delayed in our patients mainly because of
      scarce financial resources. Delayed interventions were associated with higher
      morbidity and mortality.

PMID- 20811525
TI  - Ophthalmic admissions in a tertiary hospital in Nigeria.
AB  - BACKGROUND: Hospitalization for eye care is required for different reasons. The
      pattern of admissions into the ophthalmic wards of a sub-urban tertiary hospital
      was studied. METHODOLOGY: Records of patients admitted into the Ophthalmology
      wards of the Obafemi Awolowo University Teaching Hospitals Complex Ile-Ife from
      January 2004 to December 2007 were reviewed and the age, sex, duration of
      admission and diagnosis recorded. Data was analyzed with SPSS version 13 and
      statistical significance inferred at P<0.05. RESULTS: Of the 523 patients
      admitted, 60.2% were males while 39.8% were females (P<0.0001); the male
      preponderance becomes less prominent with increasing age (P=0.001). The duration
      of admission ranged between 2 and 24 days with a mean of 2.86+/- 1.95 days and
      63% were admitted for 3 days. The main indications for admission were cataract
      (58.3%), ocular trauma (14.3%) and glaucoma (13.4%). Eye injuries were more
      common among children and young adults while cataract and glaucoma were the
      leading indications in the middle aged and elderly. CONCLUSION: Cataract, trauma
      and glaucoma were the leading indications for ophthalmic hospitalization. Human
      and infrastructural development of the ophthalmology unit should lay emphasis on
      the more prevalent needs to enhance effective and efficient management of these
      diseases.

PMID- 20811526
TI  - Integrating cervical cancer and genital tract infection screening into mother,
      child health and family planning clinics in Eldoret, Kenya.
AB  - BACKGROUND: Visual inspection, with acetic acid (VIA) and with Lugol's iodine
      (VILI), has been demonstrated to have test characteristics comparable to those of
      Pap smear but are more affordable and easier implement. It also presents an
      opportunity for management of female genital tract infection. OBJECTIVES: Pilot
      test integration of cervical cancer screening using visual inspection with
      genital tract infection identification into an existing MCH-FP in MTRH. METHODS:
      Cross sectional, descriptive study in which consecutive women were screened for
      genital tract inflammatory morbidity and cervical cancer through visual
      inspection. RESULTS: Two hundred and nineteen women with a mean age of 31-3
      years, parity of 3.1 were screened. About 54% of study participants had multiple
      sex partners, 62% had sexual debut earlier than 20 years, while use of tobacco
      was reported by 4%. The test positivity rate was 13.9% and 16.9% for VIA and VILI
      respectively. Positive test finding was significantly related to contraceptive
      never-use after controlling for previous screening (p=0.006).Symptoms of genital
      tract infections were reported by 38% of the participants with features of
      cervicitis being reported by nearly 24%. CONCLUSION: Integration of cervical
      cancer screening and genital tract infection identification and treatment into
      the existing MCH-FP appears feasible.

PMID- 20811528
TI  - Post partum haemorrhage in a teaching hospital in Nigeria: a 5-year experience.
AB  - OBJECTIVES: The aim was to determine the incidence, causes and the maternal
      mortality associated with postpartum haemorrhage in a tertiary centre in Nigeria.
      METHODS: Case records of all patients that had postpartum haemorrhage after
      vaginal delivery at Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife
      unit over a 5-year period (January 1st, 2002 to December 31st, 2006) were
      reviewed and analysed. Post-partum blood loss was calculated by estimating blood
      loses in graduated containers and in bed lines and gauze packs. RESULTS: 112
      women had postpartum haemorrhage during the period under review. 76(67.86%) had
      primary postpartum haemorrhage and 36(32.14%) had secondary postpartum
      haemorrhage. The commonest cause of post partum haemorrhage was retained products
      of conception due mismanagement of the third stage of labour, this occurred in 88
      women (78.57%) of cases. Other causes were uterine atony 12(10.71%), genital
      tract laceration 9(8.04%), disseminated intravascular coagulopathy 1(0.8%)
      puerperal sepsis 1(0.8%) and broken down episiotomy, 1(0.8%). The maternal
      mortality during the period was 90 out of which 6 were due to postpartum
      haemorrhage. CONCLUSION: Retained products of conception resulting from
      mismanagement of the third stage of labour is the most common cause of post
      partum haemorrhage in our centre.

PMID- 20811527
TI  - Anaemia in pregnancy: associations with parity, abortions and child spacing in
      primary healthcare clinic attendees in Trinidad and Tobago.
AB  - OBJECTIVE: To determine the prevalence of anaemia in antenatal clinic attendees;
      to investigate the effects of parity, age, gravidity, previous abortions, child
      spacing and other factors on the prevalence of anaemia in pregnancy. METHODS:
      This was a retrospective and cross-sectional study. Antenatal records of 2287
      pregnant women attending 40 public healthcare centres from January 2000 to
      December 2005 in Trinidad and Tobago were used. Data pertaining to the
      investigated variables were recorded. The national prevalence of anaemia was
      calculated and chi-square tests, odds ratios and logistic regression were used to
      assess the relationship between anaemia and each variable. RESULTS: The
      prevalence of anaemia was 15.3% (95% CI 13.4%, 16.6%). No significant difference
      in the prevalence of anaemia was found among the different clinics or counties.
      At the first haemoglobin reading, age was inversely related to the presence of
      anaemia, whereas gestational age at first visit was directly related. At the
      final haemoglobin reading, parity, gravidity, and previous spontaneous abortions
      were directly related to the prevalence of anaemia, while the number of visits
      was inversely related. Age was inversely associated to the severity of anaemia
      while gravidity was directly related. CONCLUSION: The prevalence of anaemia
      decreased by 18.7% from 1967. Despite this positive indication, women under 24
      years and those commencing antenatal care after the first trimester are still at
      a higher risk for developing anaemia. Early commencement of antenatal care and
      close monitoring of the risk groups identified should be strongly advocated.

PMID- 20811529
TI  - Referral practices and perceived barriers to timely obstetric care among Ugandan
      traditional birth attendants (TBA).
AB  - OBJECTIVES: To assess current beliefs, knowledge and practices of Ugandan
      traditional birth attendants (TBAs) and their pregnant patients regarding
      referral of obstructed labors and fistula cases. METHODS: Six focus groups were
      held in rural areas surrounding Kampala, the capital city of Uganda. RESULTS:
      While TBAs, particularly those with previous training, appear willing to refer
      problematic pregnancies and labors, more serious problems exist that could lessen
      any positive effects of training. These problems include reported abuse by
      doctors and nurses, and seeing fistula as a disease caused by hospitals.
      CONCLUSIONS: Training of TBAs can be helpful to standardize knowledge about and
      encourage timely emergency obstetric referrals, as well as increase knowledge
      about the causes and preventions of obstetric fistula. However, for full
      efficacy, training must be accompanied by greater collaboration between
      biomedical and traditional health personnel, and increased infrastructure to
      prevent mistreatment of pregnant patients by medical staff.

PMID- 20811530
TI  - Diagnosis and treatment of pyogenic bone infections.
AB  - BACKGROUND: Pyogenic osteomyelitis is still frequently seen in the developing
      world and the treatment of chronic osteomyelitis presents a considerable
      challenge despite advances in microbiological techniques, antibiotics and
      surgical techniques. Acute haematogenous osteomyelitis is commoner in children.
      RESULTS: In the pre-antibiotic era, mortality rate was high and progression to
      chronic osteomyelitis was common. A near similar scenario still exists in many
      developing countries due to the combination of inappropriate and/or inadequate
      antibiotic therapy, delayed presentation and unorthodox interventions by
      traditional healers. DISCUSSION: Chronic osteomyelitis may result from poorly
      treated or untreated acute osteomyelitis, open fractures, surgery for an array of
      orthopaedic conditions and from contiguous spread from infected soft tissue as
      may occur in diabetic foot infections. A large array of treatment techniques
      hinged on sequestrectomy/ debridement, management of dead space, improvement of
      oxygenation and perfusion to ischaemic tissue exist. Despite these, total
      eradication of disease is difficult. CONCLUSION: This article summarizes the
      pathology and methods of management available for pyogenic osteomyelitis. In its
      acute and chronic forms, the disease is likely to remain prevalent in the
      developing world until issues of ignorance, poverty and prompt access to
      appropriate and efficacious medical care are addressed.

PMID- 20811531
TI  - Rethinking breast cancer screening strategies in resource-limited settings.
AB  - The incidence of breast cancer in sub-Saharan nations is increasing. There is a
      worsening scarcity of Human Resource for Health in Uganda in particular and Sub
      Saharan Africa in general. Resources available for health care are predominantly
      spent on infectious disease care such as (HIV/AIDS, Tuberculosis and Malaria).
      These factors and more make the future of breast cancer care including screening
      in Sub Saharan African grim.Although mass breast cancer screening by mammography
      has been proved to be efficacious in the developed nations of the world, this has
      not been replicated in the developing nations because mass screening is not yet
      possible for the reasons stated. This paper proposes an alternative to
      mammography mass screening.Breast health programs for the most part are adhoc or
      non-existent in Uganda. The challenge of mass screening is not only limited to
      less readily available mammogram machines and trained human resources but also to
      the fact that the targeted population is of relatively young women in their 30s,
      implying that screening should commence earlier than it is practiced in nations
      where breast cancer peaks among women in their 50s. Mammography is not
      efficacious in young women with dense breast tissue. Ultra sound scans are not
      only up to 10 fold more available than mammography machines but are half the cost
      per examination.Although using ultra sound Scan for screening for non-palpable
      lumps is not up to par with standard breast cancer care mammography. It may be
      better than nothing, may be beneficial in aiding early cancer diagnosis. This
      concept is akin to the 'task shifting' advocated by WHO. It is worth
      investigating use of ultra sound scan for mass screening for breast cancer in
      resource-limited environments. This is not in any way lowering standards of
      oncologic diagnosis but filling the otherwise unattended to gap, the unmet need.

PMID- 20811533
TI  - Mucinous cystadenoma of the appendix: a case report.
AB  - INTRODUCTION: Tumours of the appendix are emerging as diseases of increasing
      concern due to a rising incidence1. We present a case of mucinous cystadenoma of
      the appendix in an elderly patient. To our knowledge, this is the first report of
      mucinous cystadenoma of the appendix from Nigeria.

PMID- 20811532
TI  - Hepatocellular carcinoma and the underlying mechanisms.
AB  - The incidence of hepatocellular carcinoma is increasing worldwide as well as the
      associated risk factors, some of which include exposure to aflatoxin B1,
      Hepatitis B (HBV) virus and hepatitis C (HCV) virus. Mutation of tumour
      suppressor gene p53 at codon 249(ser) at exon 7 has been found to contribute
      significantly to replication of damaged DNA and subsequent tumour progression.
      The x gene of HBV (HBx) is the most common open reading frame integrated into the
      host genome in hepatocellular carcinoma and the integrated HBx is frequently
      mutated in hepatocellular carcinoma. Mutant HBx proteins still retain their
      ability to bind to p53 thereby attenuating DNA repair and p53-mediated apoptosis.

PMID- 20811534
TI  - Unusual cause of thyroid abscess.
AB  - Thyroid abscess is a rare condition of the thyroid gland. The common causative
      organisms responsible for thyroid abscess are Staphylococci and Streptococci
      species. We described a case of thyroid abscess due to Klebsiella pneumoniae in
      an infant. The patient was successfully treated with open surgical drainage and
      appropriate antimicrobial agents.

PMID- 20811535
TI  - Radiofrequency catheter ablation of ventricular premature complexes.

PMID- 20811536
TI  - Embryology of the conduction system for the electrophysiologist.
AB  - It is critical for interventional electrophysiologists to thoroughly appreciate
      the topographic and developmental anatomy of the heart and its conduction system.
      Not only is understanding cardiac anatomy important to prevent complications from
      collateral damage and to help guide catheter placement, but developmental anatomy
      allows a deeper appreciation of the arrhythmogenic substrate. In this article, we
      briefly review the relevant stages of cardiac development for
      electrophysiologists. The potential location of normal and abnormal conduction
      patterns resulting from heterogeneous developmental origin is discussed.

PMID- 20811537
TI  - Anatomic guidance for ablation: atrial flutter, fibrillation, and outflow tract
      ventricular tachycardia.
AB  - After initial documentation of excellent efficacy with radiofrequency ablation,
      this procedure is being performed increasingly in more complex situations and for
      more difficult arrhythmia. In these circumstances, an accurate knowledge of the
      anatomic basis for the ablation procedure will help maintain this efficacy and
      improve safety. In this review, we discuss the relevant anatomy for
      electrophysiology interventions for typical right atrial flutter, atrial
      fibrillation, and outflow tract ventricular tachycardia. In the pediatric
      population, maintaining safety is a greater challenge, and here again, knowing
      the neighboring and regional anatomy of the arrhythmogenic substrate for these
      arrhythmias may go a long way in preventing complications.

PMID- 20811538
TI  - Premature Ventricular Contractions and Non-sustained Ventricular Tachycardia:
      Association with Sudden Cardiac Death, Risk Stratification, and Management
      Strategies.
AB  - Premature ventricular contractions (PVCs) and non-sustained ventricular
      tachycardia (NSVT) are frequently encountered and a marker of
      electrocardiomyopathy. In some instances, they increase the risk for sustained
      ventricular tachycardia, ventricular fibrillation, and sudden cardiac death.
      While often associated with a primary cardiomyopathy, they have also been known
      to cause tachycardia-induced cardiomyopathy in patients without preceding
      structural heart disease. Medical therapy including beta-blockers and class III
      anti-arrhythmic agents can be effective while implantable cardiac defibrillators
      (ICD) are indicated in certain patients. Radiofrequency ablation (RFA) is the
      preferred, definitive treatment in those patients that improve with anti
      arrhythmic therapy, have tachycardia-induced cardiomyopathy, or have certain
      subtypes of PVCs/NSVT. We present a review of PVCs and NSVT coupled with case
      presentations on RFA of fascicular ventricular tachycardia, left-ventricular
      outflow tract ventricular tachycardia, and Purkinje arrhythmia leading to
      polymorphic ventricular tachycardia.

PMID- 20811539
TI  - Transient global amnesia after ablation of premature ventricular beats arising
      from the right coronary cusp.
AB  - A 58-year-old female underwent PVC ablation within the right coronary cusp for
      symptomatic PVCs and suspected PVC-induced cardiomyopathy. Immediately after the
      procedure, she started to complain about feelings of impending doom,
      disorientation to time and place, and amnesia regarding the procedure. No sensory
      or motor deficits could be elicited. A thromboembolic event was suspected and she
      was evaluated by a neurologist. CT scan of her brain was negative. She was
      diagnosed with transient global amnesia and her mentation returned to baseline
      within 4 hours after the procedure.

PMID- 20811540
TI  - Narrow QRS Complexes in a Patient with Baseline Surgical RBBB: What is the
      Mechanism?

PMID- 20811541
TI  - Burkholderia cepacia Complex: Emerging Multihost Pathogens Equipped with a Wide
      Range of Virulence Factors and Determinants.
AB  - The Burkholderia cepacia complex (Bcc) comprises at least 17 closely-related
      species of the beta-proteobacteria subdivision, widely distributed in natural and
      man-made inhabitats. Bcc bacteria are endowed with an extraordinary metabolic
      diversity and emerged in the 1980s as life-threatening and difficult-to-treat
      pathogens among patients suffering from cystic fibrosis. More recently, these
      bacteria became recognized as a threat to hospitalized patients suffering from
      other diseases, in particular oncological patients. In the present paper, we
      review these and other traits of Bcc bacteria, as well as some of the strategies
      used to identify and validate the virulence factors and determinants used by
      these bacteria. The identification and characterization of these virulence
      factors is expected to lead to the design of novel therapeutic strategies to
      fight the infections caused by these emergent multidrug resistant human
      pathogens.

PMID- 20811542
TI  - Parenteral antibiotics reduce bifidobacteria colonization and diversity in
      neonates.
AB  - We investigated the impact of parenteral antibiotic treatment in the early
      neonatal period on the evolution of bifidobacteria in the newborn. Nine babies
      treated with intravenous ampicillin/gentamicin in the first week of life and nine
      controls (no antibiotic treatment) were studied. Denaturing gradient gel
      electrophoresis was used to investigate the composition of Bifidobacterium in
      stool samples taken at four and eight weeks. Bifidobacteria were detected in all
      control infants at both four and eight weeks, while only six of nine antibiotic
      treated infants had detectable bifidobacteria at four weeks and eight of nine at
      eight weeks. Moreover, stool samples of controls showed greater diversity of
      Bifidobacterium spp. compared with antibiotic-treated infants. In conclusion,
      short-term parenteral antibiotic treatment of neonates causes a disturbance in
      the expected colonization pattern of bifidobacteria in the first months of life.
      Further studies are required to probiotic determine if supplementation is
      necessary in this patient group.

PMID- 20811543
TI  - Enteral nutrition and acute pancreatitis: a review.
AB  - Introduction. In patients with acute pancreatitis (AP), nutritional support is
      required if normal food cannot be tolerated within several days. Enteral
      nutrition is preferred over parenteral nutrition. We reviewed the literature
      about enteral nutrition in AP. Methods. A MEDLINE search of the English language
      literature between 1999-2009. Results. Nasogastric tube feeding appears to be
      safe and well tolerated in the majority of patients with severe AP, rendering the
      concept of pancreatic rest less probable. Enteral nutrition has a beneficial
      influence on the outcome of AP and should probably be initiated as early as
      possible (within 48 hours). Supplementation of enteral formulas with glutamine or
      prebiotics and probiotics cannot routinely be recommended. Conclusions. Nutrition
      therapy in patients with AP emerged from supportive adjunctive therapy to a
      proactive primary intervention. Large multicentre studies are needed to confirm
      the safety and effectiveness of nasogastric feeding and to investigate the role
      of early nutrition support.

PMID- 20811544
TI  - Malnutrition in surgical wards: a plea for concern.
AB  - Background. Malnutrition in hospitalized patients is underdiagnosed, with 30 to
      60% of patients admitted being malnourished. The objective of this study was to
      investigate the nutritional status of patients in a general surgery ward and to
      define the correlation between the risk of malnutrition and the hospital course
      and clinical outcome. Study design. The study group included 100 consecutive
      patients admitted to a general surgery ward who were ambulant and could undergo
      the Malnutrition Universal Screening Tool (MUST). Results. Thirty-two patients
      (33%) had aMUST score of 2 or higher, and were therefore defined at high
      malnutrition risk. The patients at risk had longer hospitalization and worse
      outcome. The length of stay of the malnourished patients was significantly longer
      than that of patients without malnutrition risk (18.8 +/- 11.5 vs. 7 +/- 5.3
      days, P = .003). Mortality in the high-risk group was higher overall, in
      hospital, and after six months and one year of followup. Conclusions. Medical
      personnel must be aware that malnutrition afflicts even patients whose background
      is not suggestive of malnutrition. Best results are achieved when cooperation of
      all staff members is enlisted, because malnutrition has severe consequences and
      can be treated easily.

PMID- 20811546
TI  - Hyperglycemia in hospitalized patients receiving parental nutrition is associated
      with increased morbidity and mortality: a review.
AB  - Parenteral Nutrition (PN) is a valuable life saving intervention which can
      improve the nutritional status of hospitalized malnourished patients. PN is
      associated with complications including the development of hyperglycemia. This
      paper aims to provide a descriptive systematic review regarding the effects of PN
      induced hyperglycemia in hospitalized patients, either in the intensive care unit
      or ward, while formulating and complementing existing guidelines on the
      administration of PN and glucose monitoring in hospitalized patients. Medline and
      Pubmed were searched for relevant articles describing complications arising from
      the development of hyperglycemia in patients receiving PN; four relevant studies
      were identified in the search. These articles had different glycemic targets and
      patient populations, and their protocols varied with regards to glycemic control.
      However, there was consistency regarding the association between hyperglycemia
      and mortality in patients receiving PN. These studies highlight the need for
      guidelines regarding monitoring and initiation of therapy in hyperglycemic
      patients. Unfortunately, all the currently available studies are retrospective in
      design; a large, prospective, randomized controlled trial regarding glycemic
      control in patients receiving PN is required for the development of standardized
      protocols.

PMID- 20811545
TI  - Diagnosis and management of oropharyngeal Dysphagia and its nutritional and
      respiratory complications in the elderly.
AB  - Oropharyngeal dysphagia is a major complaint among older people. Dysphagia may
      cause two types of complications in these patients: (a) a decrease in the
      efficacy of deglutition leading to malnutrition and dehydration, (b) a decrease
      in deglutition safety, leading to tracheobronchial aspiration which results in
      aspiration pneumonia and can lead to death. Clinical screening methods should be
      used to identify older people with oropharyngeal dysphagia and to identify those
      patients who are at risk of aspiration. Videofluoroscopy (VFS) is the gold
      standard to study the oral and pharyngeal mechanisms of dysphagia in older
      patients. Up to 30% of older patients with dysphagia present aspiration-half of
      them without cough, and 45%, oropharyngeal residue; and 55% older patients with
      dysphagia are at risk of malnutrition. Treatment with dietetic changes in bolus
      volume and viscosity, as well as rehabilitation procedures can improve
      deglutition and prevent nutritional and respiratory complications in older
      patients. Diagnosis and management of oropharyngeal dysphagia need a
      multidisciplinary approach.

PMID- 20811547
TI  - Propofol-Based Sedation Does Not Increase Rate of Complication during
      Percutaneous Endoscopic Gastrostomy Procedure.
AB  - Objectives. To evaluate and compare the complication rate of sedation with or
      without propofol regimen for percutaneous endoscopic gastrostomy (PEG) in a
      hospital in Thailand. Subjects and Methods. A total of 198 patients underwent PEG
      procedures by using intravenous sedation (IVS) from Siriraj Hospital, Thailand
      from August 2006 to January 2009. The primary outcome variable was the overall
      complication rate. The secondary outcome variables were sedation and procedure
      related complications, and mortality rate. Results. After matching ASA physical
      status and indications of procedure, there were 92 PEG procedures in propofol
      based sedation group (A) and 20 PEG procedures in non-propofol based sedation
      group (B). All sedation was given by residents or anesthetic nurses directly
      supervised by staff anesthesiologist in the endoscopy room. There were no
      significant differences in patients' characteristics, sedation time, indication,
      complications, anesthetic personnel and mortality rate between the two groups.
      All complications were easily treated, with no adverse sequelae. Mean dose of
      fentanyl and midazolam in group A was significantly lower than in group B.
      Conclusion. Propofol-based sedation does not increase rate of complication during
      PEG procedure. Additionally, IVS of PEG procedure is relatively safe and
      effective when performed by physicians in training. Serious complications are
      none.

PMID- 20811549
TI  - Uro-oncological controversies in euro-oncology: highlights from the European
      association of urology section of oncological urology, january 15-17, 2010,
      vienna, austria.

PMID- 20811548
TI  - Venous thromboembolism in urologic surgery: prophylaxis, diagnosis, and
      treatment.
AB  - Venous thromboembolism (VTE) represents one of the most common and potentially
      devastating complications of urologic surgery. With VTE's rapid onset of
      symptoms, association with a precipitous clinical course, and high mortality
      rate, all urologists should be well versed in appropriate prophylaxis, prompt
      diagnosis, and expeditious treatment. A MEDLINE(R) search was performed for
      articles that examined the incidence, diagnosis, and treatment of VTE in urologic
      surgery. Additional articles were reviewed based on cited references. There is a
      paucity of prospective studies on VTE in the urologic literature with most
      recommendations for urologic surgery patients being extrapolated from other
      surgical disciplines. Retrospective studies place VTE incidence rates in major
      urologic surgeries among the highest reported-highlighting the importance of
      thromboprophylaxis. Conversely, VTE was rarely reported in association with
      endoscopic and laparoscopic procedures making mechanical thromboprophylaxis
      sufficient. Recent literature reveals delayed VTE occurring after hospital
      discharge to be a persistent threat despite inpatient preoperative prophylaxis.
      Computed tomographic angiography has emerged as the test of choice for diagnosing
      pulmonary embolism, whereas lower extremity duplex sonography is recommended for
      diagnosing deep venous thrombosis. Traditional angiography is rarely used.
      Treatment of VTE involves therapeutic anticoagulation for various lengths of time
      based on presence and reversibility of patient risk factors as well as number of
      events. Perioperative thromboprophylaxis should be considered in all major
      urologic surgeries. Urologists should be familiar with incidence rates,
      recommended prophylaxis, appropriate diagnosis, and treatment recommendations for
      VTE to minimize morbidity and mortality. The limited number of prospective,
      randomized, controlled trials evaluating the use of thromboprophylaxis in
      urologic surgery demonstrates the need for further research.

PMID- 20811550
TI  - Oncological update: new findings in bladder and prostate cancer: highlights from
      the 25th anniversary congress of the European association of urology, april 16
      20, 2010, barcelona, Spain.

PMID- 20811551
TI  - Best of the AUA Annual Meeting: Highlights From the 2010 American Urological
      Association Meeting, May 29-June 3, 2010, San Francisco, CA.

PMID- 20811552
TI  - Risk factor analysis and management of ureteral double-j stent complications.
AB  - Double-J ureteral stents are commonly used to manage urinary obstructions. Pain,
      bladder irritative symptoms, and fever are usually signs of early complications
      related to double-J stents; late complications are more troublesome. We review 4
      cases that highlight a variety of late complications with double-J stents
      (encrustation, migration, and fragmentation). Following a review of the
      literature, guidelines are established for monitoring potential risk factors as
      well as management strategies for prevention of possible complications when using
      double-J stents.

PMID- 20811553
TI  - The effects of bariatric surgery on the kidneys.

PMID- 20811554
TI  - Female urology-future and present.

PMID- 20811555
TI  - Can urinary nerve growth factor be a biomarker for overactive bladder?
AB  - The clinical diagnosis of overactive bladder (OAB) greatly varies and is based on
      subjective symptoms. A more objective method to diagnose and assess therapeutic
      outcome in OAB patients, especially for health care providers not trained in
      urology, needs to be found. Evidence has shown that urinary proteins such as
      nerve growth factor (NGF) and prostaglandin E(2) levels increase in patients with
      OAB, bladder outlet obstruction, and detrusor overactivity. Urinary NGF level
      increases physiologically in normal subjects at urge to void, but increases
      pathologically in OAB patients at a small bladder volume and with a sensation of
      urgency. Recent studies have shown that patients with OAB dry and OAB wet have
      significantly higher urinary NGF levels compared with control groups and patients
      with increased bladder sensation. Urinary NGF levels decrease after
      antimuscarinic therapy and further decrease after detrusor botulinum toxin
      injections in refractory OAB. Urinary NGF level could be a potential biomarker
      for diagnosis of OAB and assessment of the therapeutic effect of antimuscarinic
      therapy. The latest medical advances in this field are reviewed herein.

PMID- 20811556
TI  - Forensic dissection of a clinical trial: lessons learned in understanding and
      managing interstitial cystitis.
AB  - A pharmaceutical company-sponsored post-registration clinical trial designed to
      determine the most effective dose of pentosan polysulfate for the treatment of
      interstitial cystitis (IC) reported negative results. However, because of a
      priori trial design features, important posthoc analyses were able to answer many
      of the important clinical issues on the epidemiology, diagnosis, and treatment of
      IC that to date had remained unanswered. Seven published follow-up reports based
      on data and outcomes from the original study evaluated the clinical significance
      of a positive Potassium Sensitivity Test, confirmed the O'Leary-Sant Interstitial
      Cystitis Symptom Index as a valid and sensitive outcome measure, and determined
      that doses of pentosan polysulfate higher than the standard US Food and Drug
      Administration-approved dose of 300 mg/d did not increase efficacy although
      increased duration of therapy increases the chance of symptom amelioration.
      Further analyses determined that sexual dysfunction is an important parameter to
      assess in IC and that successful therapy can improve sexual functioning. Finally,
      the data showed that symptom severity, quality of life (QoL), and sleep function
      are interrelated. Consequently, symptom improvement with therapy correlates with
      improvement in both sleep function and QoL. This post hoc forensic dissection of
      a clinical trial initially undertaken for simple regulatory reasons has
      significantly improved our understanding and management of the enigmatic
      condition we call IC.

PMID- 20811557
TI  - Kidney stones: a global picture of prevalence, incidence, and associated risk
      factors.
AB  - The prevalence and incidence of nephrolithiasis is reported to be increasing
      across the world. Herein, we review information regarding stone incidence and
      prevalence from a global perspective. A literature search using PubMed and Ovid
      was performed to identify peer-reviewed journal articles containing information
      on the incidence and prevalence of kidney stones. Key words used included kidney
      stone prevalence, incidence, and epidemiology. Data were collected from the
      identified literature and sorted by demographic factors and time period. A total
      of 75 articles were identified containing kidney stone-related incidence or
      prevalence data from 20 countries; 34 provided suitable information for review.
      Data regarding overall prevalence or incidence for more than a single time period
      were found for 7 countries (incidence data for 4 countries; prevalence data for 5
      countries). These included 5 European countries (Italy, Germany, Scotland, Spain,
      and Sweden), Japan, and the United States. The body of evidence suggests that the
      incidence and prevalence of kidney stones is increasing globally. These increases
      are seen across sex, race, and age. Changes in dietary practices may be a key
      driving force. In addition, global warming may influence these trends.

PMID- 20811558
TI  - Surgical options for drug-refractory overactive bladder patients.
AB  - Overactive bladder (OAB) is a symptom complex of urinary frequency, urinary
      urgency, and nocturia, with or without urgency incontinence. This syndrome is
      idiopathic in most instances without clearly defined pathophysiology. Studies
      clearly show that OAB negatively impacts health-related quality of life and
      impairs daily functioning in a large proportion of patients. Despite recent
      advances in drug delivery and improved tolerability of antimuscarinic drug class,
      a large percentage of patients remain refractory to conventional pharmacological
      therapy for this chronic condition. There are several unique and effective
      treatments that are available for this difficult population. We review the
      various surgical options within the urological armamentarium to treat patients
      with refractory OAB.

PMID- 20811559
TI  - Endoscopic Treatment of Vesicoureteral Reflux in Children with
      Dextranomer/Hyaluronic Acid-A Single Surgeon's 6-Year Experience.
AB  - Endoscopic treatment for vesicoureteral reflux (VUR) has become an established
      alternative to long-term antibiotic prophylaxis and ureteral reimplantation. We
      present the outcome of endoscopic treatment with dextranomer/hyaluronic acid
      copolymer (Deflux) for VUR in children by a single surgeon at our institute from
      October 2003 to October 2009. We reviewed the cases of 150 patients (total 239
      ureters), 56 girls (37%) and 94 boys (63%), with a mean age of 2.2 years and a
      median followup of 2.5 years (range 3-68 months). Among the 239 ureters treated,
      67.4% (161/239) were cured with a single injection, and a second and third
      injection raised the cure rate to 86.6% (207/239) and 88.3% (211/239),
      respectively. None had postoperative ureteral obstruction.

PMID- 20811560
TI  - Cavitated conglomerate mass in silicosis indicating associated tuberculosis.
AB  - Silicosis is the most common occupational lung disease worldwide. It leads to
      respiratory impairment and may have associated infections that decrease pulmonary
      function. We describe the case of a 55-year-old man with chronic silicosis who
      presented with hemoptysis and a cavitated conglomerate mass. The final diagnosis
      was silicotuberculosis.

PMID- 20811561
TI  - Persistent CSF Rhinorrhoea, Pneumocephalus, and Recurrent Meningitis Following
      Misdiagnosis of Olfactory Neuroblastoma.
AB  - A 41-year-old female patient was admitted with streptococcal meningitis on a
      background of 5-month history of CSF rhinorrhoea. Imaging revealed an extensive
      skull base lesion involving the sphenoid and ethmoid sinuses, the pituitary fossa
      with suprasellar extension and bony destruction. Histological examination of an
      endonasal transethmoidal biopsy suggested a diagnosis of olfactory neuroblastoma.
      A profuse CSF leak occurred and the patient developed coliform meningitis. A
      second endonasal endoscopic biopsy was undertaken which demonstrated the tumour
      to be a prolactinoma. Following endonasal repair of the CSF leak and lumbar
      drainage, she developed profound pneumocephalus. The patient underwent three
      further unsuccessful CSF leak repairs. Definitive control of the CSF leak was
      finally achieved through a transcranial approach with prolonged lumbar drainage.
      This case illustrates some of the potentially devastating complications which can
      occur as a consequence of complex skull base lesions. A multidisciplinary
      approach may be required to successfully manage such cases.

PMID- 20811562
TI  - Reversible Cortical Blindness as a Prominent Manifestation of Cerebral Embolism
      due to Infective Endocarditis.
AB  - Introduction. Infective endocarditis in the left heart may be complicated by
      stroke, due to embolisation from infectious valvular vegetations. Infarction of
      both occipital lobes, which are supplied by the posterior cerebral arteries, is
      infrequent, and is the cause of cortical blindness from lesion of the visual
      cortex. Cortical blindness is characterized by intact pupillary reflexes, a
      normal fundoscopy, and, rarely, denial of visual loss. Case Presentation. We
      report the case of a 58-year-old woman, recipient of a mechanical aortic valve,
      who presented with fever, multiple organ dysfunction, and cortical blindness.
      Transesophageal echocardiography and blood cultures confirmed the diagnosis of
      infective endocarditis caused by methicillin-sensitive Staphylococcus aureus.
      Computed tomography of the brain without contrast revealed the presence of
      infarctions in both occipital lobes. It is noteworthy that the visual loss
      resolved after treatment of endocarditis. Conclusions. A stroke occurring in a
      patient presenting with fever and a history of valvular heart disease strongly
      suggests the presence of infective endocarditis. Bilateral thromboembolic
      infarcts of the occipital lobes cause cortical blindness, that can resolve after
      treatment of endocarditis.

PMID- 20811563
TI  - Acanthosis nigricans in a patient with lung cancer: a case report.
AB  - Some skin lesions may accompany malignancies. Acanthosis nigricans, one such
      lesion, is a paraneoplastic dermatosis characterized by hyperpigmented and
      velvety verrucose plaques observed as symetric eruptions. With this report, we
      aim to present a rare case of concomitant lung cancer and acanthosis nigricans.
      Malignant acanthosis nigricans is most commonly associated with intra-abdominal
      malignancies. A 65-year-old patient who had hyperpigmented, hypertrophic and
      symmetric verrucose lesions at the flexor surfaces of the lower and upper
      extremities, face, palms and the axillary region. Thoracic computed tomography
      demonstrated a hypodense mass lesion with a dimension of 5 x 5.5 cm at the center
      of basal segment bronchi of the left pulmonary lobe. Fiberoptic bronchoscopy
      showed that the access to the lower left lobe was almost completely obstructed by
      the endobronchial lesion. The result of the histopathologic examination of the
      endobronchial tissue biopsy was reported as non-small cell (adenocarcinoma) lung
      cancer. Result of the histopathologic analysis of the punch biopsy of the skin
      lesions was reported as acanthosis nigricans .There are no pathognomonic
      dermatological findings for lung cancer. In conclusion, there are skin lesions
      that accompany lung cancer and we believe that these should be considered for
      differential diagnosis.

PMID- 20811564
TI  - Diagnostic tests for Alzheimer's disease: rationale, methodology, and challenges.
AB  - There has been a large increase in the amount of research seeking to define or
      diagnose Alzheimer's disease before patients develop dementia. If successful,
      this would principally have clinical benefits both in terms of treatment as well
      as risk modification. Moreover, a better method for diagnosing predementia
      disease would assist research which seeks to develop such treatments and risk
      modification strategies. The evidence-based definition of a diagnostic test's
      accuracy is fundamental to achieve the above goals and to address this, the
      Cochrane Collaboration has established a Diagnostic Test Accuracy group dedicated
      to examining the utility and accuracy of proposed tests in dementia and cognitive
      impairment. We present here the assumptions and observations underpinning the
      chosen methodology as well as the initial methodological approach decided upon.

PMID- 20811565
TI  - Inferior ST-Elevation Myocardial Infarction Associated with Takotsubo
      Cardiomyopathy.
AB  - Takotsubo cardiomyopathy (TCM) is usually characterized by transient left
      ventricular apical ballooning. Due to the clinical symptoms which include chest
      pain, electrocardiographic changes, and elevated myocardial markers, Takotsubo
      cardiomyopathy is frequently mimicking ST-elevation myocardial infarction in the
      absence of a significant coronary artery disease. Otherwise an acute occlusion of
      the left anterior descending coronary artery can produce a typical Takotsubo
      contraction pattern. ST-elevation myocardial infarction (STEMI) is frequently
      associated with emotional stress, but to date no cases of STEMI triggering TCM
      have been reported. We describe a case of a female patient with inferior ST
      elevation myocardial infarction complicated by TCM.

PMID- 20811566
TI  - Frontiers in life science.

PMID- 20811567
TI  - Inherited adaptation of genome-rewired cells in response to a challenging
      environment.
AB  - Despite their evolutionary significance, little is known about the adaptation
      dynamics of genomically rewired cells in evolution. We have confronted yeast
      cells carrying a rewired regulatory circuit with a severe and unforeseen
      challenge. The essential HIS3 gene from the histidine biosynthesis pathway was
      placed under the exclusive regulation of the galactose utilization system.
      Glucose containing medium strongly represses the GAL genes including HIS3 and
      these rewired cells are required to operate this essential gene. We show here
      that although there were no adapted cells prior to the encounter with glucose, a
      large fraction of cells adapted to grow in this medium and this adaptation was
      stably inherited. The adaptation relied on individual cells that switched into an
      adapted state and, thus, the adaptation was due to a response of many individual
      cells to the change in environment and not due to selection of rare advantageous
      phenotypes. The adaptation of numerous individual cells by heritable phenotypic
      switching in response to a challenge extends the common evolutionary framework
      and attests to the adaptive potential of regulatory circuits.

PMID- 20811568
TI  - Biological markers and Alzheimer disease: a canadian perspective.
AB  - Decreased beta-amyloid(1-42) and increased phospho-tau protein levels in the
      cerebrospinal fluid (CSF) are currently the most accurate chemical
      neurodiagnostics of sporadic Alzheimer disease (AD). A report (2007) of the Third
      Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (2006)
      recommended that biological markers should not be currently requisitioned by
      primary care physicians in the routine investigation of subjects with memory
      complaints. Consideration for such testing should prompt patient referral to a
      specialist engaged in dementia evaluations or a Memory Clinic. The specialist
      should consider having CSF biomarkers (beta-amyloid(1-42) and phospho-tau)
      measured at a reputable facility in restricted cases presenting with atypical
      features and diagnostic confusion, but not as a routine procedure in all
      individuals with typical sporadic AD phenotypes. We submit that developments in
      the field of AD biomarker discovery since publication of the 3rd CCCDTD consensus
      data do not warrant revision of the 2007 recommendations.

PMID- 20811569
TI  - SOD1 Is Essential for the Viability of DT40 Cells and Nuclear SOD1 Functions as a
      Guardian of Genomic DNA.
AB  - Reactive oxygen species (ROSs) are produced during normal cellular metabolism,
      particularly by respiration in mitochondria, and these ROSs are considered to
      cause oxidative damage to macromolecules, including DNA. In our previous paper,
      we found no indication that depletion of mitochondrial superoxide dismutase,
      SOD2, resulted in an increase in DNA damage. In this paper, we examined SOD1,
      which is distributed in the cytoplasm, nucleus, and mitochondrial intermembrane
      space. We generated conditional SOD1 knockout cells from chicken DT40 cells and
      analyzed their phenotypes. The results revealed that SOD1 was essential for
      viability and that depletion of SOD1, especially nuclear SOD1, increased sister
      chromatid exchange (SCE) frequency, suggesting that superoxide is generated in or
      near the nucleus and that nuclear SOD1 functions as a guardian of the genome.
      Furthermore, we found that ascorbic acid could offset the defects caused by SOD1
      depletion, including cell lethality and increases in SCE frequency and
      apurinic/apyrimidinic sites.

PMID- 20811570
TI  - Adult Onset Still's Disease and Rocky Mountain Spotted Fever.
AB  - Adult Still's Disease was first described in 1971 by Bywaters in fourteen adult
      female patients who presented with symptoms indistinguishable from that of
      classic childhood Still's Disease (Bywaters, 1971). George Still in 1896 first
      recognized this triad of quotidian (daily) fevers, evanescent rash, and arthritis
      in children with what later became known as juvenile inflammatory arthritis
      (Still, 1990). Adult Onset Still's Disease (AOSD) is an inflammatory condition of
      unknown etiology characterized by an evanescent rash, quotidian fevers, and
      arthralgias. Numerous infectious agents have been associated with its
      presentation. This case is to our knowledge the first presentation of AOSD in the
      setting of Rocky Mountain Spotted Fever. Although numerous infectious agents have
      been suggested, the etiology of this disorder remains elusive. Nevertheless,
      infection may in fact play a role in triggering the onset of symptoms in those
      with this disorder. Our case presentation is, to our knowledge, the first case of
      Adult Onset Still's Disease associated with Rocky Mountain spotted fever (RMSF).

PMID- 20811571
TI  - Unifocal Granuloma of Femur due to Langerhans' Cell Histiocytosis: A Case Report
      and Review of the Literature.
AB  - The radiological diagnosis of osteolytic lesions of the long bones in pediatric
      population constitutes a challenge when the case history and clinical data are
      uncharacteristic. We believe that the description of few clinically and
      histologically proven cases to verify the existence of radiological signs useful
      for diagnosis may be of interest. Here, we describe a case of Langerhans' cell
      histiocytosis (LCH) presenting as unifocal eosinophilic granuloma of femur along
      with a brief review of the literature.

PMID- 20811572
TI  - Nail-patella syndrome associated with short stature: a case series.
AB  - Introduction. Nail-patella syndrome (NPS) is a rare genetic disorder that is
      characterized by a pleiotropic malformation affecting the nail, the skeleton, and
      occasionally the central nervous system and the kidneys. Case Presentation. We
      report two paediatric cases, which are of two sisters, who aged, respectively,
      two and five years. They are admitted to explore short stature. The initial
      clinical examination and radiologic findings confirmed the diagnosis of Nail
      patella syndrome. Conclusion. Skeletal, ophthalmologic, and renal involvements
      were mostly associated with NPS. The association with short stature was
      exceptional.

PMID- 20811573
TI  - A rare case of traumatic bilateral fibular head fractures.
AB  - Avulsion fibular head fractures are rare. There is only one reference of
      bilateral fibular fractures after epileptic seizure. We aim to present the
      mechanism and the treatment of this rare injury. We present the case of a 30-year
      old woman who was hit by a car on the anteromedial side of both knees. Clinical
      and radiographic control showed bilateral fibular head fractures. Knee
      instability was not found at both knees and MRI did not show any concomitant
      ligament ruptures. Bone bruises of both medial condyles found in MRI explain the
      mechanism of this injury. The patient was treated conservatively with functional
      knee braces for 6 weeks allowing full range of motion, but otherwise mobilised as
      normal without any support. Six weeks after the trauma, there were no symptoms
      while the fractures sites had united completely after 6 months. One year
      postinjury the patient was free from symptoms.

PMID- 20811574
TI  - Posterior interosseous nerve palsy caused by parosteal lipoma: a case report.
AB  - An 83-year-old woman presented with weakness in her right-hand and wrist
      extensors and swelling in the proximal part of the right forearm.
      Electromyography (EMG) confirmed involvement of posterior interosseous nerve at
      the level of proximal forearm. MR imaging demonstrated the characteristics of
      lipoma which extended on the anterolateral aspect of the right forearm and at the
      level of the radius neck. The lesion was parosteal lipoma causing compression and
      paralysis of the posterior interosseous nerve without sensory deficit. In this
      paper, posterior interosseous nerve palsy due to compression of a parosteal
      lipoma recovered after excision of the lipoma followed by intensive
      rehabilitation for six month. Surgical excision should be performed to ensure
      optimal recovery from the nerve paralysis.

PMID- 20811575
TI  - Global Egr1-miRNAs binding analysis in PMA-induced K562 cells using ChIP-Seq.
AB  - Although much is known about microRNAs' regulation in gene expression and their
      contributions in cell fate, to date, globally lineage-(cell-) specific
      identification of the binding events between a transcription factor and its
      targeting microRNA genes is still waiting for elucidation. In this paper, we
      performed a ChIP-Seq experiment to find the targeting microRNA genes of a
      transcription factor, Egr1, in human erythroleukemia cell line K562. We found
      Egr1 binding sites near the promoters of 124 distinct microRNA genes, accounting
      for about 42% of the miRNAs which have high-confidence predicted promoters (294).
      We also found EGR1 bind to another 63 pre-miRNAs. We chose 12 of the 187
      microRNAs with Egr1 binding sites to perform ChIP-PCR assays and the positive
      binding signal from ChIP-PCR confirmed the ChIP-Seq results. Our experiments
      provide the first global binding profile between Egr1 and its targeting microRNA
      genes in PMA-treated K562 cells, which may facilitate the understanding of
      pathways controlling microRNA biology in this specific cell line.

PMID- 20811576
TI  - Peritoneal hydatidosis.
AB  - Secondary peritoneal hydatidosis is caused by spontaneous or iatrogenic rupture
      of hepatic echinococcal cysts. We describe the case of a 65-year-old Tunisian
      male patient with previous history of liver hydatidosis who presented to our
      attention with subocclusive status. Imaging revealed a retrovesical hydatid cyst,
      adherent to the sigmoid colon. The treatment of choice was surgical removal of
      the cyst and the sigmoid colon. The patient is now being closely followed up.

PMID- 20811577
TI  - Mapping drug physico-chemical features to pathway activity reveals molecular
      networks linked to toxicity outcome.
AB  - The identification of predictive biomarkers is at the core of modern toxicology.
      So far, a number of approaches have been proposed. These rely on statistical
      inference of toxicity response from either compound features (i.e., QSAR), in
      vitro cell based assays or molecular profiling of target tissues (i.e.,
      expression profiling). Although these approaches have already shown the potential
      of predictive toxicology, we still do not have a systematic approach to model the
      interaction between chemical features, molecular networks and toxicity outcome.
      Here, we describe a computational strategy designed to address this important
      need. Its application to a model of renal tubular degeneration has revealed a
      link between physico-chemical features and signalling components controlling cell
      communication pathways, which in turn are differentially modulated in response to
      toxic chemicals. Overall, our findings are consistent with the existence of a
      general toxicity mechanism operating in synergy with more specific single-target
      based mode of actions (MOAs) and provide a general framework for the development
      of an integrative approach to predictive toxicology.

PMID- 20811578
TI  - Herpesvirus vectors for therapy of brain tumors.
AB  - Genetically modified, conditionally-replicating Herpes Simplex Virus Type 1 (HSV
      1) vectors for the treatment of malignant glioma have provided encouraging
      results in the handful of Phase I and Phase II clinical trials conducted to date.
      In recent years, a number of new strategies have been developed to improve anti
      tumor activity of these attenuated vectors, through either introduction of
      foreign gene inserts to enhance tumor killing through a variety of mechanisms, or
      through combination with existing treatment regimens, including radiation and/or
      chemotherapeutics. Another promising new approach has been the engineering of
      novel oncolytic HSV vectors that retain wildtype replication, but are targeted to
      tumor cells through a variety of mechanisms. This review summarizes the latest
      advances in herpesvirus-mediated oncolytic therapies from both preclinical
      results and clinical trials with oncolytic HSV vectors in patients, and their
      implication for design of future trials.

PMID- 20811579
TI  - Herpesvirus vectors in gene therapy.

PMID- 20811581
TI  - Threshold Graph Limits and Random Threshold Graphs.
AB  - We study the limit theory of large threshold graphs and apply this to a variety
      of models for random threshold graphs. The results give a nice set of examples
      for the emerging theory of graph limits.

PMID- 20811580
TI  - Herpes simplex virus type 1/adeno-associated virus hybrid vectors.
AB  - Herpes simplex virus type 1 (HSV-1) amplicons can accommodate foreign DNA of any
      size up to 150 kbp and, therefore, allow extensive combinations of genetic
      elements. Genomic sequences as well as cDNA, large transcriptional regulatory
      sequences for cell type-specific expression, multiple transgenes, and genetic
      elements from other viruses to create hybrid vectors may be inserted in a modular
      fashion. Hybrid amplicons use genetic elements from HSV-1 that allow replication
      and packaging of the vector DNA into HSV-1 virions, and genetic elements from
      other viruses that either direct integration of transgene sequences into the host
      genome or allow episomal maintenance of the vector. Thus, the advantages of the
      HSV-1 amplicon system, including large transgene capacity, broad host range,
      strong nuclear localization, and availability of helper virus-free packaging
      systems are retained and combined with those of heterologous viral elements that
      confer genetic stability to the vector DNA. Adeno-associated virus (AAV) has the
      unique capability of integrating its genome into a specific site, designated
      AAVS1, on human chromosome 19. The AAV rep gene and the inverted terminal repeats
      (ITRs) that flank the AAV genome are sufficient for this process. HSV-1 amplicons
      have thus been designed that contain the rep gene and a transgene cassette
      flanked by AAV ITRs. These HSV/AAV hybrid vectors direct site-specific
      integration of transgene sequences into AAVS1 and support long-term transgene
      expression.

PMID- 20811582
TI  - The effect of opioid receptor blockade on the neural processing of thermal
      stimuli.
AB  - The endogenous opioid system represents one of the principal systems in the
      modulation of pain. This has been demonstrated in studies of placebo analgesia
      and stress-induced analgesia, where anti-nociceptive activity triggered by pain
      itself or by cognitive states is blocked by opioid antagonists. The aim of this
      study was to characterize the effect of opioid receptor blockade on the
      physiological processing of painful thermal stimulation in the absence of
      cognitive manipulation. We therefore measured BOLD (blood oxygen level dependent)
      signal responses and intensity ratings to non-painful and painful thermal stimuli
      in a double-blind, cross-over design using the opioid receptor antagonist
      naloxone. On the behavioral level, we observed an increase in intensity ratings
      under naloxone due mainly to a difference in the non-painful stimuli. On the
      neural level, painful thermal stimulation was associated with a negative BOLD
      signal within the pregenual anterior cingulate cortex, and this deactivation was
      abolished by naloxone.

PMID- 20811583
TI  - Autophagy Blockade Sensitizes Prostate Cancer Cells towards Src Family Kinase
      Inhibitors.
AB  - There is overwhelming evidence that tyrosine kinases play an important role in
      cancer development. As a prototype of targeted therapy, tyrosine kinase
      inhibitors are now successfully applied to cancer treatment. However, as single
      agents, tyrosine kinase inhibitors have not achieved satisfactory results in the
      treatment of prostate cancer, principally due to their inability to efficiently
      kill tumor cells. The authors' laboratory has been interested in the role of the
      Src complex in prostate cancer progression, including the induction of androgen
      independence and metastasis. Previously, the authors reported that Src inhibitors
      such as saracatinib and PP2 caused G1 growth arrest and diminished invasiveness
      in prostate cancer cells but rarely apoptosis. Here, they have shown that Src
      family kinase (SFK) inhibitors can induce a high level of autophagy, which
      protects treated cells from undergoing apoptosis. Src siRNA knockdown experiments
      confirmed that autophagy was indeed caused by the lack of Src activity. The SFK
      inhibitor-induced autophagy is accompanied by the inhibition of the PI3K (type
      I)/Akt/mTOR signaling pathway. To test whether autophagy blockade could lead to
      enhanced cell death, pharmacological inhibitors (3-methyladenine and chloroquine)
      and a genetic inhibitor (siRNA targeting Atg7) were used in combination with SFK
      inhibitors. The results showed that autophagy inhibition effectively enhanced
      cell killing induced by SFK inhibitors. Importantly, the authors showed that a
      combination of saracatinib with chloroquine in mice significantly reduced
      prostate cancer (PC3) xenograft growth compared with the control group. Taken
      together, these data suggest that (1) autophagy serves a protective role in SFK
      inhibitor-mediated cell killing, and (2) clinically acceptable autophagy
      modulators may be used beneficially as adjunctive therapeutic agents for SFK
      inhibitors.

PMID- 20811584
TI  - Early severe inflammatory responses to uropathogenic E. coli predispose to
      chronic and recurrent urinary tract infection.
AB  - Chronic infections are an increasing problem due to the aging population and the
      increase in antibiotic resistant organisms. Therefore, understanding the host
      pathogen interactions that result in chronic infection is of great importance.
      Here, we investigate the molecular basis of chronic bacterial cystitis. We
      establish that introduction of uropathogenic E. coli (UPEC) into the bladders of
      C3H mice results in two distinct disease outcomes: resolution of acute infection
      or development of chronic cystitis lasting months. The incidence of chronic
      cystitis is both host strain and infectious dose-dependent. Further, development
      of chronic cystitis is preceded by biomarkers of local and systemic acute
      inflammation at 24 hours post-infection, including severe pyuria and bladder
      inflammation with mucosal injury, and a distinct serum cytokine signature
      consisting of elevated IL-5, IL-6, G-CSF, and the IL-8 analog KC. Mice deficient
      in TLR4 signaling or lymphocytes lack these innate responses and are resistant,
      to varying degrees, to developing chronic cystitis. Treatment of C3H mice with
      the glucocorticoid anti-inflammatory drug dexamethasone prior to UPEC infection
      also suppresses the development of chronic cystitis. Finally, individuals with a
      history of chronic cystitis, lasting at least 14 days, are significantly more
      susceptible to redeveloping severe, chronic cystitis upon bacterial challenge.
      Thus, we have discovered that the development of chronic cystitis in C3H mice by
      UPEC is facilitated by severe acute inflammatory responses early in infection,
      which subsequently are predisposing to recurrent cystitis, an insidious problem
      in women. Overall, these results have significant implications for our
      understanding of how early host-pathogen interactions at the mucosal surface
      determines the fate of disease.

PMID- 20811586
TI  - A molecular analysis of mutations at the complex dumpy locus in Drosophila
      melanogaster.
AB  - The Drosophila dumpy gene consists of seventy eight coding exons and encodes a
      huge extracellular matrix protein containing large numbers of epidermal growth
      factor-like (EGF) modules and a novel module called dumpy (DPY). A molecular
      analysis of forty five mutations in the dumpy gene of Drosophila melanogaster was
      carried out. Mutations in this gene affect three phenotypes: wing shape, thoracic
      cuticular defects, and lethality. Most of the mutations were chemically induced
      in a single dumpy allele and were analyzed using a nuclease that cleaves single
      base pair mismatches in reannealed duplexes followed by dHPLC. Additionally,
      several spontaneous mutations were analyzed. Virtually all of the chemically
      induced mutations, except for several in a single exon, either generate nonsense
      codons or lesions that result in downstream stop codons in the reading frame. The
      remaining chemically induced mutations remove splice sites in the nascent dumpy
      message. We propose that the vast majority of nonsense mutations that affect all
      three basic dumpy phenotypes are in constitutive exons, whereas nonsense mutants
      that remove only one or two of the basic functions are in alternatively spliced
      exons. Evolutionary comparisons of the dumpy gene from seven Drosophila species
      show strong conservation of the 5' ends of exons where mutants with partial dumpy
      function are found. In addition, reverse transcription PCR analyses reveal
      transcripts in which exons marked by nonsense mutations with partial dumpy
      function are absent.

PMID- 20811585
TI  - Characterizing the metabolism of Dehalococcoides with a constraint-based model.
AB  - Dehalococcoides strains respire a wide variety of chloro-organic compounds and
      are important for the bioremediation of toxic, persistent, carcinogenic, and
      ubiquitous ground water pollutants. In order to better understand metabolism and
      optimize their application, we have developed a pan-genome-scale metabolic
      network and constraint-based metabolic model of Dehalococcoides. The pan-genome
      was constructed from publicly available complete genome sequences of
      Dehalococcoides sp. strain CBDB1, strain 195, strain BAV1, and strain VS. We
      found that Dehalococcoides pan-genome consisted of 1118 core genes (shared by
      all), 457 dispensable genes (shared by some), and 486 unique genes (found in only
      one genome). The model included 549 metabolic genes that encoded 356 proteins
      catalyzing 497 gene-associated model reactions. Of these 497 reactions, 477 were
      associated with core metabolic genes, 18 with dispensable genes, and 2 with
      unique genes. This study, in addition to analyzing the metabolism of an
      environmentally important phylogenetic group on a pan-genome scale, provides
      valuable insights into Dehalococcoides metabolic limitations, low growth yields,
      and energy conservation. The model also provides a framework to anchor and
      compare disparate experimental data, as well as to give insights on the
      physiological impact of "incomplete" pathways, such as the TCA-cycle, CO(2)
      fixation, and cobalamin biosynthesis pathways. The model, referred to as iAI549,
      highlights the specialized and highly conserved nature of Dehalococcoides
      metabolism, and suggests that evolution of Dehalococcoides species is driven by
      the electron acceptor availability.

PMID- 20811587
TI  - Accelerated SPECT Monte Carlo Simulation Using Multiple Projection Sampling and
      Convolution-Based Forced Detection.
AB  - Monte Carlo (MC) is a well-utilized tool for simulating photon transport in
      single photon emission computed tomography (SPECT) due to its ability to
      accurately model physical processes of photon transport. As a consequence of this
      accuracy, it suffers from a relatively low detection efficiency and long
      computation time. One technique used to improve the speed of MC modeling is the
      effective and well-established variance reduction technique (VRT) known as forced
      detection (FD). With this method, photons are followed as they traverse the
      object under study but are then forced to travel in the direction of the detector
      surface, whereby they are detected at a single detector location. Another method,
      called convolution-based forced detection (CFD), is based on the fundamental idea
      of FD with the exception that detected photons are detected at multiple detector
      locations and determined with a distance-dependent blurring kernel. In order to
      further increase the speed of MC, a method named multiple projection convolution
      based forced detection (MP-CFD) is presented. Rather than forcing photons to hit
      a single detector, the MP-CFD method follows the photon transport through the
      object but then, at each scatter site, forces the photon to interact with a
      number of detectors at a variety of angles surrounding the object. This way, it
      is possible to simulate all the projection images of a SPECT simulation in
      parallel, rather than as independent projections. The result of this is vastly
      improved simulation time as much of the computation load of simulating photon
      transport through the object is done only once for all projection angles.The
      results of the proposed MP-CFD method agrees well with the experimental data in
      measurements of point spread function (PSF), producing a correlation coefficient
      (r(2)) of 0.99 compared to experimental data. The speed of MP-CFD is shown to be
      about 60 times faster than a regular forced detection MC program with similar
      results.

PMID- 20811588
TI  - Constitutive and Inducible Innate Responses in Cells Infected by HSV-1-Derived
      Amplicon Vectors.
AB  - Amplicons are helper-dependent herpes simplex virus type 1 (HSV-1)-based vectors
      that can deliver very large foreign DNA sequences and, as such, are good
      candidates both for gene delivery and vaccine development. However, many studies
      have shown that innate constitutive or induced cellular responses, elicited or
      activated by the entry of HSV-1 particles, can play a significant role in the
      control of transgenic expression and in the induction of inflammatory responses.
      Moreover, transgene expression from helper-free amplicon stocks is often weak and
      transient, depending on the particular type of infected cells, suggesting that
      cellular responses could be also responsible for the silencing of amplicon
      mediated transgene expression. This review summarizes the current experimental
      evidence underlying these latter concepts, focusing on the impact on transgene
      expression of very-early interactions between amplicon particles and the infected
      cells, and speculates on possible ways to counteract the cellular protective
      mechanisms, thus allowing stable transgene expression without enhancement of
      vector toxicity.

PMID- 20811589
TI  - In-hospital mortality of disseminated tuberculosis in patients infected with the
      human immunodeficiency virus.
AB  - BACKGROUND: Tuberculosis (TB) is a cause of significant morbidity and mortality
      in patients with AIDS. The goal of our study was to determine predictors of in
      hospital mortality in patients with AIDS and disseminated tuberculosis in a
      middle-income country. MATERIAL AND METHODS: We conducted a retrospective cohort
      study in a tertiary care center, for patients with AIDS in southern Brazil. From
      1996 to 2008, all patients with the diagnosis of disseminated TB were included.
      RESULTS: Eighty patients were included. In-hospital mortality was 35% (N = 28).
      On multivariate Cox regression analysis, low basal albumin (P < .01) was
      associated with death, and fever at admission was related to better survival (P <
      .01). CONCLUSION: Albumin levels or fever are independent predictors of survival
      in patients with HIV and disseminated TB. They can serve as indirect markers of
      immunodeficiency in patients with disseminated TB and AIDS.

PMID- 20811590
TI  - Cardiopulmonary Collapse during Labour.
AB  - Cardiopulmonary collapse during labour is a catastrophic event caused by various
      medical, surgical and obstetrical conditions. It is an emergency that threatens
      the life of the mother and her unborn child. We present a case of a pregnant
      woman who suffered from preeclampsia and underwent induction of labour. Severe
      lung edema occurred early in labour that caused cardiopulmonary collapse.
      Advanced heart-lung resuscitation was established immediately and continued until
      an emergency cesarean section was performed few minutes later. The outcome was
      favourable for both mother and child. We further discuss some aspects of the
      pathophysiology and appropriate treatment of cardiorespiratory arrest during
      labour, which involves the coordinated action of the obstetric, pediatric and
      surgical ward personnel.

PMID- 20811591
TI  - The influence of pregnancy on the recurrence of cutaneous malignant melanoma in
      women.
AB  - Objective. The aim of this study was to determine whether pregnancy increases the
      recurrence risk of cutaneous malignant melanoma (CMM) in women with a history of
      stage I CMM. Methods. The electronic medical databases of Medline and Embase were
      explored. All 1084 obtained articles were screened on title and abstract using
      predetermined inclusion and exclusion criteria. A critical appraisal of relevance
      and validity was conducted on the remaining full text available articles.
      Results. Two studies were selected. Both studies revealed no significant
      difference in disease-free survival between women with stage I CMM and the
      control population. Conclusion. Pregnancy does not increase the recurrence risk
      of CMM in women with a history of stage I CMM.

PMID- 20811592
TI  - A Rare Case of Soft-Tissue Infection Caused by Raoultella planticola.
AB  - Raoultella species are Gram-negative, non-motile bacilli primarily considered to
      be environmental bacteria. Raoultella planticola is a rare cause of human
      infections. We report a case of serious soft-tissue infection in a young male
      tiler who presented with cellulitis of his left thumb. He had sustained a crush
      injury to his left thumb 10 days earlier in a soiled environment. He noted a
      minor break in the skin and he washed the wound out with running water. One week
      later, he experienced pain, erythema, and swelling of his thumb and attended his
      general practitioner who prescribed oral flucloxacillin and penicillin V. Despite
      this treatment, he noticed progressive erythema and swelling of his thumb
      requiring hospital admission 3 days later. He underwent washout and debridement
      of his thumb. Tissue obtained intraoperatively cultured Raoultella planticola. He
      was treated with broad-spectrum antibiotics including ciprofloxacin and made a
      full and rapid recovery.

PMID- 20811594
TI  - Vascular neurology nurse practitioner provision of telemedicine consultations.
AB  - Objective. The objective was to define and evaluate a role for the Vascular
      Neurology-Nurse Practitioner (VN-NP) in the delivery of telemedicine
      consultations in partnership with a vascular neurologist. Methods. Prospective
      stroke alert patients at participating hospitals underwent a two-way audio video
      telemedicine consultation with a VN-NP at a remotely located stroke center in
      partnership with a vascular neurologist. Demographic information, National
      Institutes of Health Stroke Scale (NIHSS) scores, diagnoses, CT contraindications
      to thrombolysis, thrombolysis eligibility, and time interval data were collected.
      The inter-rater agreement between VN-NP and vascular neurologist assessments was
      calculated. Results. Ten patients were evaluated. Four were determined to have
      ischemic stroke, one had a transient ischemic attack, two had intracerebral
      hemorrhages, and three were stroke mimics. Overall, three patients received
      thrombolysis. The inter-rater agreement between VN-NP and vascular neurologist
      assessments were excellent, ranging from 0.9 to 1.0. The duration of VN-NP
      consultation was 53.2 +/- 9.0 minutes, which included the vascular neurologist
      supervisory evaluation time of 12.0 +/- 9.6 minutes. Conclusion. This study
      illustrated that a stroke center VN-NP, in partnership with a vascular
      neurologist, could deliver timely telemedicine consultations, accurate diagnoses,
      and correct treatments in acute stroke patients who presented to remotely located
      rural emergency departments within a hub and spoke network. VN-NPs may fulfill
      the role of a telestroke provider.

PMID- 20811593
TI  - Partial purification and characterization of the mode of action of enterocin S37:
      a bacteriocin produced by Enterococcus faecalis S37 isolated from poultry feces.
AB  - The aim of this research was to purify and characterize the mode of action of
      enterocin S37, a bacteriocin produced by Enterococcus faecalis S37, a strain
      recently isolated from the chicken feces. Enterocin S37 has a molecular weight
      comprised between 4 and 5 kDa. It remained active after 1 h at 80(o)C and at pH
      values ranging from 4.0 to 9.0. Furthermore, cell-free supernatant of
      Enterococcus faecalis S37 and purified enterocin S37 were active against Gram
      positive bacteria including Listeria monocytogenes EGDe, L. innocua F,
      Enterococcus faecalis JH2-2, and Lactobacillus brevis F145. The purification of
      enterocin S37 was performed by ammonium sulfate precipitation followed up by
      hydrophobic-interaction chromatography procedures. Treatment of enterocin S37
      with proteinase K, alpha-chymotrypsin, and papain confirmed its proteinaceous
      nature, while its treatment with lysozyme and lipase resulted in no alteration of
      activity. Enterocin S37 is hydrophobic, anti-Listeria and likely acting by
      depletion of intracellular K(+) ions upon action on K(ATP) channels. This study
      contributed to gain more insights into the mode of action of enterocins.

PMID- 20811595
TI  - Blood glucose levels and performance in a sports cAMP for adolescents with type 1
      diabetes mellitus: a field study.
AB  - Background. Acute hypo- and hyperglycemia causes cognitive and psychomotor
      impairment in individuals with type 1 diabetes mellitus (T1DM) that may affect
      sports performance. Objective. To quantify the effect of concurrent and
      antecedent blood glucose concentrations on sports skills and cognitive
      performance in youth with T1DM attending a sports camp. Design/Methods. 28 youth
      (ages 6-17 years) attending a sports camp carried out multiple skill-based tests
      (tennis, basketball, or soccer skills) with glucose monitoring over 4 days.
      Glucose levels at the time of testing were categorized as (a) hypoglycemic (<3.6
      mM); (b) within an acceptable glycemic range (3.6-13.9 mM); or (c) hyperglycemic
      (>13.9 mM). Results. Overall, sports performance skill was approximately 20%
      lower when glucose concentrations were hypoglycemic compared to either acceptable
      or hyperglycemic at the time of skill testing (P < .05). During Stroop testing,
      "reading" and "color recognition" also degraded during hypoglycemia, while
      "interference" scores improved (P < .05). Nocturnal hypoglycemia was present in
      66% of subjects, lasting an average of 84 minutes, but this did not affect sports
      skill performance the following day. Conclusions. Mild hypoglycemia markedly
      reduces sports skill performance and cognition in young athletes with T1DM.

PMID- 20811596
TI  - Sleep and metabolism: an overview.
AB  - Sleep and its disorders are increasingly becoming important in our sleep deprived
      society. Sleep is intricately connected to various hormonal and metabolic
      processes in the body and is important in maintaining metabolic homeostasis.
      Research shows that sleep deprivation and sleep disorders may have profound
      metabolic and cardiovascular implications. Sleep deprivation, sleep disordered
      breathing, and circadian misalignment are believed to cause metabolic
      dysregulation through myriad pathways involving sympathetic overstimulation,
      hormonal imbalance, and subclinical inflammation. This paper reviews sleep and
      metabolism, and how sleep deprivation and sleep disorders may be altering human
      metabolism.

PMID- 20811597
TI  - H2AX Phosphorylation: Its Role in DNA Damage Response and Cancer Therapy.
AB  - Double-strand breaks (DSBs) are the most deleterious DNA lesions, which, if left
      unrepaired, may have severe consequences for cell survival, as they lead to
      chromosome aberrations, genomic instability, or cell death. Various physical,
      chemical, and biological factors are involved in DSB induction. Cells respond to
      DNA damage by activating the so-called DNA damage response (DDR), a complex
      molecular mechanism developed to detect and repair DNA damage. The formation of
      DSBs triggers activation of many factors, including phosphorylation of the
      histone variant H2AX, producing gammaH2AX. Phosphorylation of H2AX plays a key
      role in DDR and is required for the assembly of DNA repair proteins at the sites
      containing damaged chromatin as well as for activation of checkpoints proteins
      which arrest the cell cycle progression. In general, analysis of gammaH2AX
      expression can be used to detect the genotoxic effect of different toxic
      substances. When applied to clinical samples from cancer patients, evaluation of
      gammaH2AX levels may allow not only to monitor the efficiency of anticancer
      treatment but also to predict of tumor cell sensitivity to DNA damaging
      anticancer agents and toxicity of anticancer treatment toward normal cells.

PMID- 20811598
TI  - Therapeutic improvement of scarring: mechanisms of scarless and scar-forming
      healing and approaches to the discovery of new treatments.
AB  - Scarring in the skin after trauma, surgery, burn or sports injury is a major
      medical problem, often resulting in loss of function, restriction of tissue
      movement and adverse psychological effects. Whilst various studies have utilised
      a range of model systems that have increased our understanding of the pathways
      and processes underlying scar formation, they have typically not translated to
      the development of effective therapeutic approaches for scar management. Existing
      treatments are unreliable and unpredictable and there are no prescription drugs
      for the prevention or treatment of dermal scarring. As a consequence, scar
      improvement still remains an area of clear medical need. Here we describe the
      basic science of scar-free and scar-forming healing, the utility of pre-clinical
      model systems, their translation to humans, and our pioneering approach to the
      discovery and development of therapeutic approaches for the prophylactic
      improvement of scarring in man.

PMID- 20811600
TI  - Ectopic intrauterine device in the bladder of a pregnant woman.
AB  - Background. Uterine perforation and transvesical migration of an intrauterine
      device are rare complications. Case. A 28-year-old woman who had an intrauterine
      device was admitted to our outpatient clinic with complaints of amenorrhea
      lasting 5 weeks and pelvic pain lasting a year. Transvaginal ultrasonography
      revealed embedding of the intrauterine device in the bladder. The misplaced
      device was removed by laparotomy. Conclusion. The followup of intrauterine device
      localization with transvaginal ultrasonography is essential for early detection
      of possible serious complications.

PMID- 20811599
TI  - Organogenic nodule formation in hop: a tool to study morphogenesis in plants with
      biotechnological and medicinal applications.
AB  - The usage of Humulus lupulus for brewing increased the demand for high-quality
      plant material. Simultaneously, hop has been used in traditional medicine and
      recently recognized with anticancer and anti-infective properties. Tissue culture
      techniques have been reported for a wide range of species, and open the prospect
      for propagation of disease-free, genetically uniform and massive amounts of
      plants in vitro. Moreover, the development of large-scale culture methods using
      bioreactors enables the industrial production of secondary metabolites. Reliable
      and efficient tissue culture protocol for shoot regeneration through organogenic
      nodule formation was established for hop. The present review describes the
      histological, and biochemical changes occurring during this morphogenic process,
      together with an analysis of transcriptional and metabolic profiles. We also
      discuss the existence of common molecular factors among three different
      morphogenic processes: organogenic nodules and somatic embryogenesis, which
      strictly speaking depend exclusively on intrinsic developmental reprogramming,
      and legume nitrogen-fixing root nodules, which arises in response to symbiosis.
      The review of the key factors that participate in hop nodule organogenesis and
      the comparison with other morphogenic processes may have merit as a study
      presenting recent advances in complex molecular networks occurring during
      morphogenesis and together, these provide a rich framework for biotechnology
      applications.

PMID- 20811601
TI  - Promoting moderate-vigorous physical activity in overweight minority girls.
AB  - There is limited research on the types of activities that are most effective for
      promoting MVPA in children. Purpose. To assess which types of activities elicit
      MVPA in overweight minority girls. Methods. Sample consisted of 31 overweight
      (BMI >/= 85th percentile) Latina and African-American girls (mean age 10.3 +/-
      1.2 years). Participants wore an Actical accelerometer each day for 8 hours for
      15 days to assess engagement in MVPA during their participation in a three-week
      activity intervention that included traditional fitness, sport skills, games,
      dancing, and flexibility sessions. Results. On average 62% of participants met
      the MVPA recommended guidelines (60 min/5d/wk) with an average of 68.5 +/- 14
      minutes of MVPA across the three weeks. Traditional fitness sessions elicited the
      highest percent of MVPA (mean time spent in MVPA = 32%), followed by dancing and
      games (mean time spent in MVPA = 21%), sports skills (mean time spent in MVPA =
      18%), and flexibility (mean time spent in MVPA = 7%). Step aerobics and rumba
      fitness elicited the highest proportions of MVPA. Conclusion. Traditional fitness
      activities were identified as the most successful in eliciting MVPA in overweight
      Latina and African American girls.

PMID- 20811602
TI  - Dermoscopic Features of Pigmented Bowen's Disease in a Japanese Female Mimicking
      Malignant Melanoma.
AB  - Various structures have been reported for dermoscopic features of pigmented
      Bowen's disease (BD), which could be a mimic of various pigmented skin lesions. A
      79-year-old Japanese woman presented with a 3-year history of brown-black macule
      on her right upper arm without symptom. Dermoscopic examination demonstrated
      irregular flossy streaks, irregular brown dots/globules, blue-whitish regression
      structures, and overlaying whitish scaly areas. We suspected pigmented skin
      lesions including seborrheic keratosis, pigmented eccrine poroma, and malignant
      melanoma and excised completely with a 5 mm margin. Histopathological features
      were consistent with a diagnosis of pigmented BD. Although similar dermoscopic
      features might be revealed in pigmented skin lesions and it may occasionally be
      difficult to distinguish between pigmented BD and other pigmented skin lesions,
      dermoscopy would be useful in speculating pathologic features of pigmented BD.

PMID- 20811603
TI  - Clinical effectiveness of an anesthesiologist-administered intravenous sedation
      outside of the main operating room for pediatric upper gastrointestinal endoscopy
      in Thailand.
AB  - Objectives. To review our sedation practice and to evaluate the clinical
      effectiveness of an anesthesiologist-administered intravenous sedation outside of
      the main operating room for pediatric upper gastrointestinal endoscopy (UGIE) in
      Thailand. Subjects and Methods. We undertook a retrospective review of the
      sedation service records of pediatric patients who underwent UGIE. All
      endoscopies were performed by a pediatric gastroenterologist. All sedation was
      administered by staff anesthesiologist or anesthetic personnel. Results. A total
      of 168 patients (94 boys and 74 girls), with age from 4 months to 12 years,
      underwent 176 UGIE procedures. Of these, 142 UGIE procedures were performed with
      intravenous sedation (IVS). The mean sedation time was 23.2 +/- 10.0 minutes.
      Propofol was the most common sedative drugs used. Mean dose of propofol,
      midazolam and fentanyl was 10.0 +/- 7.5 mg/kg/hr, 0.2 +/- 0.2 mg/kg/hr, and 2.5
      +/- 1.2 mcg/kg/hr, respectively. Complications relatively occurred frequently.
      All sedations were successful. However, two patients became more deeply than
      intended and required unplanned endotracheal intubation. Conclusion. The study
      shows the clinical effectiveness of an anesthesiologist-administered IVS outside
      of the main operating room for pediatric UGIE in Thailand. All complications are
      relatively high. We recommend the use of more sensitive equipments such as end
      tidal CO(2) and carefully select more appropriate patients.

PMID- 20811604
TI  - Therapies with emerging evidence of efficacy: avotermin for the improvement of
      scarring.
AB  - Many patients are dissatisfied with scars on both visible and non-visible body
      sites and would value any opportunity to improve or minimise scarring following
      surgery. Approximately 44 million procedures in the US and 42 million procedures
      in the EU per annum could benefit from scar reduction therapy. A wide range of
      non-invasive and invasive techniques have been used in an attempt to improve
      scarring although robust, prospective clinical trials to support the efficacy of
      these therapies are lacking. Differences in wound healing and scar outcome
      between early fetal and adult wounds led to interest in the role of the TGFbeta
      family of cytokines in scar formation and the identification of TGFbeta3
      (avotermin) as a potential therapeutic agent for the improvement of scar
      appearance. Extensive pre-clinical and human Phase I and II clinical trial
      programmes have confirmed the scar improving efficacy of avotermin which produces
      macroscopic and histological improvements in scar architecture, with improved
      restitution of the epidermis and an organisation of dermal extracellular matrix
      that more closely resembles normal skin. Avotermin is safe and well tolerated and
      is currently in Phase III of clinical development, with the first study, in
      patients undergoing scar revision surgery, fully recruited.

PMID- 20811606
TI  - Gossypiboma: retained surgical sponge after a gynecologic procedure.
AB  - We report on a case of gossypiboma. A 54-year-old woman was admitted to our
      hospital with abdominal mass. She had undergone a caesarean operation 23 years
      previously. The mass in the right abdominal quadrant was suspected by abdominal
      computed tomography and magnetic resonance imaging. The mass was removed by
      laparotomy excision and the final diagnosis was gossypiboma.

PMID- 20811607
TI  - Renal cell carcinoma presenting with cutaneous metastasis: a case report.
AB  - Renal cell carcinoma is the most common kidney tumor in adults. Cutaneous
      metastasis is a rare first symptom of the disease. This paper describes the
      diagnosis of a renal cell carcinoma that was indicated by cutaneous metastasis in
      the head and neck region, and considers the etiopathogenesis of such cases. A
      careful skin examination is important to detect cutaneous metastasis associated
      with renal cell carcinomas. Metastatic skin lesions in the head and neck region
      must be taken into consideration during a differential diagnosis.

PMID- 20811608
TI  - Mild to moderate functional tricuspid regurgitation: retrospective comparison of
      surgical and conservative treatment.
AB  - Background. Unoperated severe tricuspid regurgitation (TR) leads to the right
      ventricle (RV) failure. We wanted to determine if there was near-term
      postoperative progression of noncorrected mild to moderate functional TR in
      patients who underwent mitral valve surgery for chronic significant mitral
      regurgitation (MR) and if RV size and function were affected. Methods and
      Results. We compared two groups of patients retrospectively. In the first group
      (TVA+, n = 45), tricuspid valve annuloplasty (TVA) had been performed in
      conjunction with either mitral valve replacement (MVR) or mitral valve repair
      (MVP). The second group (TVA-, n = 22) underwent MVP or MVR without TVA. TVA+
      group revealed a significant decrease in TR and right ventricle diameter. In the
      TVA- group, 7 patients (32%) showed a significant progression, by one or more
      grades, of noncorrected TR together with dilatation and decreased ejection
      fraction of the right ventricle. Conclusions. Tricuspid annuloplasty performed
      concurrently with MVP or MVR can prevent subsequent progression of tricuspid
      regurgitation along with right ventricular dilatation and systolic dysfunction in
      the near-term postoperative period.

PMID- 20811605
TI  - Nanotargeted radionuclides for cancer nuclear imaging and internal radiotherapy.
AB  - Current progress in nanomedicine has exploited the possibility of designing tumor
      targeted nanocarriers being able to deliver radionuclide payloads in a site or
      molecular selective manner to improve the efficacy and safety of cancer imaging
      and therapy. Radionuclides of auger electron-, alpha-, beta-, and gamma-radiation
      emitters have been surface-bioconjugated or after-loaded in nanoparticles to
      improve the efficacy and reduce the toxicity of cancer imaging and therapy in
      preclinical and clinical studies. This article provides a brief overview of
      current status of applications, advantages, problems, up-to-date research and
      development, and future prospects of nanotargeted radionuclides in cancer nuclear
      imaging and radiotherapy. Passive and active nanotargeting delivery of
      radionuclides with illustrating examples for tumor imaging and therapy are
      reviewed and summarized. Research on combing different modes of selective
      delivery of radionuclides through nanocarriers targeted delivery for tumor
      imaging and therapy offers the new possibility of large increases in cancer
      diagnostic efficacy and therapeutic index. However, further efforts and
      challenges in preclinical and clinical efficacy and toxicity studies are required
      to translate those advanced technologies to the clinical applications for cancer
      patients.

PMID- 20811609
TI  - Day care general anaesthesia for a child with bardet-biedl syndrome.
AB  - Bardet-Biedl syndrome is a very rare autosomal-recessive disorder with pan
      systemic effects. The perioperative period may be hazardous for patients with
      this disorder. We describe the presenting features and management of a child who
      was scheduled for elective ambulatory general anesthesia and discuss the relevant
      points for the busy anesthesiologist.

PMID- 20811610
TI  - Chronic kidney disease and mortality in implantable cardioverter-defibrillator
      recipients.
AB  - Incidence of sudden cardiac death (SCD) in end-stage renal disease (ESRD) remains
      high. Limited data is available about whether implantable cardioverter
      defibrillators (ICDs) can prevent arrhythmic death in patients with chronic
      kidney disease (CKD). The purpose of this retrospective study was to determine
      the impact of CKD on all-cause and sudden cardiac death in ICD recipients. We
      evaluated 441 consecutive patients who underwent ICD implantation at our center
      between 1994 and 2002. We found that mortality rate was higher in patients with
      eGFR <60 mL/min and those with ESRD on hemodialysis (43%, n = 69/162 and 54%, n =
      12/22, resp.) than in patients with eGFR >/=60 mL/min (23%, n = 58/257; P <
      .0005). The SCD rate was also higher in the patients with ESRD (50%) than in CKD
      patients not on dialysis (10.2%; P < .0005). Mortality rate for single-chamber
      ICDs was 56.8% in comparison with dual-chamber ICDs (38.1%) and for biventricular
      ICDs (5.0%) (P < .0005).

PMID- 20811611
TI  - Computational Identification of Novel MicroRNAs and Their Targets in Vigna
      unguiculata.
AB  - MicroRNAs (miRNAs) are a class of endogenous, noncoding, short RNAs directly
      involved in regulating gene expression at the posttranscriptional level. High
      conservation of miRNAs in plant provides the foundation for identification of new
      miRNAs in other plant species through homology alignment. Here, previous known
      plant miRNAs were BLASTed against the Expressed Sequence Tag (EST) and Genomic
      Survey Sequence (GSS) databases of Vigna unguiculata, and according to a series
      of filtering criteria, a total of 47 miRNAs belonging to 13 miRNA families were
      identified, and 30 potential target genes of them were subsequently predicted,
      most of which seemed to encode transcription factors or enzymes participating in
      regulation of development, growth, metabolism, and other physiological processes.
      Overall, our findings lay the foundation for further researches of miRNAs
      function in Vigna unguiculata.

PMID- 20811612
TI  - Small-bowel capsule endoscopy in patients with suspected Crohn's disease
      diagnostic value and complications.
AB  - BACKGROUND: The aim of this work was to assess the value of capsule enteroscopy
      in the diagnosis of patients with suspected Crohn's Disease (CD). Methods. This
      was a retrospective study in a single tertiary care centre involving patients
      undergoing capsule enteroscopy for suspected CD. Patients taking nonsteroidal
      anti inflammatory drugs during the thirty preceding days or with a follow-up
      period of less than six months were excluded. Results. Seventy eight patients
      were included. The endoscopic findings included mucosal breaks in 50%, ulcerated
      stenosis in 5%, and villous atrophy in 4%. The diagnosis of CD was established in
      31 patients. The sensitivity, specificity, positive and negative predictive value
      of the endoscopic findings were 93%, 80%, 77%, and 94%, respectively. Capsule
      retention occurred in four patients (5%). The presence of ulcerated stenosis was
      significantly more frequent in patients with positive inflammatory markers. The
      diagnostic yield of capsule enteroscopy in patients with negative ileoscopy was
      56%, with a diagnostic acuity of 93%. CONCLUSIONS: Small bowel capsule endoscopy
      is a safe and valid technique for assessing patients with suspected CD. Capsule
      retention is more frequent in patients with positive inflammatory markers.
      Patients with negative ileoscopy and suspected CD should be submitted to capsule
      enteroscopy.

PMID- 20811613
TI  - The Fetal Heart in Twin-to-Twin Transfusion Syndrome.
AB  - Twin-to-twin transfusion syndrome is a severe complication occurring in 10% of
      monochorionic twin pregnancies. The disease is usually explained as due to an
      intrauterine imbalance in intertwin blood exchange, which leads to a volume
      depleted-donor twin and an overfilled recipient twin. The recipient has signs of
      cardiac dysfunction, which can be measured using echocardiography or blood and
      amniotic fluid derived biomarkers. Whereas cardiac dysfunction typically
      progresses in pregnancies treated with amniodrainage, it usually disappears
      within a few weeks after fetoscopic laser coagulation of the connecting intertwin
      anastomoses. Nevertheless, recipients remain at a increased risk of pulmonary
      stenosis. In this paper, we summarize the cardiac alterations in twin-to-twin
      transfusion syndrome, describe the changes seen after fetal therapy, list the
      newly proposed staging systems based on fetal cardiac function, and make
      recommendations about the use of fetal echocardiography in the evaluation and
      followup of pregnancies complicated by twin-to-twin transfusion syndrome.

PMID- 20811614
TI  - Comparison of four polymerase chain reaction methods for the rapid detection of
      human fecal pollution in marine and inland waters.
AB  - We compared the effectiveness of three PCR protocols for the detection of
      Bifidobacterium adolescentis and one PCR protocol for detecting Bacteroidales as
      indicators of human fecal pollution in environmental samples. Quantitative PCR
      indicated that a higher concentration of B. adolescentis DNA was recovered from
      sewage samples on the 0.2 mum filters compared to the 0.45 mum filters, and there
      was no evidence of qPCR inhibitors in the DNA extracts. With the Matsuki method
      (1999), B. adolescentis was detected only in undiluted sewage samples. The King
      method (2007) performed well and detected B. adolescentis in all of the sewage
      dilutions (from undiluted to 10(-4)). In contrast, the Bonjoch approach (2004)
      was effective at detecting B. adolescentis at lower dilutions (10(-3)) of sewage
      samples and it gave false positive results with some (3/8) pig fecal samples.
      Human-specific Bacteroidales (HuBacs) were detected in the lower diluents of
      sewage samples but was positive in pig (6/8) and cattle fecal samples. PCR
      detection of B. adolescentis in marine samples from Puerto Rico and freshwater
      samples from Georgia indicated that the PCR method of King et al. (2007) and the
      modified Layton method for HuBac were in agreement in detecting human fecal
      pollution in most sites.

PMID- 20811615
TI  - Toll-like receptors in hepatic ischemia/reperfusion and transplantation.
AB  - The family of Toll-like receptors (TLRs) function as pattern-recognition
      receptors (PRRs) that respond to a myriad of highly conserved ligands. These
      substrates include pathogen-associated molecular patterns (PAMPs) for the
      recognition of invading pathogens, as well as damage-associated molecular
      patterns (DAMPs) for the recognition of endogenous tissue injury. While the
      functions of TLRs are diverse, they have received much attention for their roles
      in ischemia/reperfusion (I/R) injury of the liver and other organs. The TLRs play
      central roles in sensing tissue damage and activating the innate immune system
      following I/R. Engagement of TLRs by endogenous DAMPs activates proinflammatory
      signaling pathways leading to the production of cytokines, chemokines and further
      release of endogenous danger signals. This paper focuses on the most recent
      findings regarding TLR family members in hepatic I/R injury and transplantation.

PMID- 20811616
TI  - Extensive lysine methylation in hyperthermophilic crenarchaea: potential
      implications for protein stability and recombinant enzymes.
AB  - In eukarya and bacteria, lysine methylation is relatively rare and is catalysed
      by sequence-specific lysine methyltransferases that typically have only a single
      protein target. Using RNA polymerase purified from the thermophilic crenarchaeum
      Sulfolobus solfataricus, we identified 21 methyllysines distributed across 9
      subunits of the enzyme. The modified lysines were predominantly in alpha-helices
      and showed no conserved sequence context. A limited survey of the Thermoproteus
      tenax proteome revealed widespread modification with 52 methyllysines in 30
      different proteins. These observations suggest the presence of an unusual lysine
      methyltransferase with relaxed specificity in the crenarchaea. Since lysine
      methylation is known to enhance protein thermostability, this may be an
      adaptation to a thermophilic lifestyle. The implications of this modification for
      studies and applications of recombinant crenarchaeal enzymes are discussed.

PMID- 20811618
TI  - Laparoscopic repair of postoperative perineal hernia.
AB  - Perineal hernias are infrequent complications following abdominoperineal
      operations. Various approaches have been described for repair of perineal hernias
      including open transabdominal, transperineal or combined abdominoperineal
      repairs. The use of laparoscopic transabdominal repair of perineal hernias is not
      well-described. We present a case report demonstrating the benefits of
      laparoscopic repair of perineal hernia following previous laparoscopic
      abdominoperineal resection (APR) using a nonabsorbable mesh to repair the defect.
      We have demonstrated that the use of laparoscopy with repair of the pelvic floor
      defect using a non absorbable synthetic mesh offers an excellent alternative with
      many potential advantages over open transabdominal and transperineal repairs.

PMID- 20811619
TI  - Thar she blows! A novel method for DNA collection from cetacean blow.
AB  - BACKGROUND: Molecular tools are now widely used to address crucial management and
      conservation questions. To date, dart biopsying has been the most commonly used
      method for collecting genetic data from cetaceans; however, this method has some
      drawbacks. Dart biopsying is considered inappropriate for young animals and has
      recently come under scrutiny from ethical boards, conservationists, and the
      general public. Thus, identifying alternative genetic collection techniques for
      cetaceans remains a priority, especially for internationally protected species.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated whether blow
      sampling, which involves collecting exhalations from the blowholes of cetaceans,
      could be developed as a new less invasive method for DNA collection. Our current
      methodology was developed using six bottlenose dolphins, Tursiops truncatus,
      housed at the National Aquarium, Baltimore (USA), from which we were able to
      collect both blow and blood samples. For all six individuals, we found that their
      mitochondrial and microsatellite DNA profile taken from blow, matched their
      corresponding mitochondrial and microsatellite DNA profile collected from blood.
      This indicates that blow-sampling is a viable alternative method for DNA
      collection. CONCLUSION/SIGNIFICANCE: In this study, we show that blow-sampling
      provides a viable and less invasive method for collection of genetic data, even
      for small cetaceans. In contrast to dart biopsying, the advantage of this method
      is that it capitalizes on the natural breathing behaviour of dolphins and can be
      applied to even very young dolphins. Both biopsy and blow-sampling require close
      proximity of the boat, but blow-sampling can be achieved when dolphins
      voluntarily bow-ride and involves no harmful contact.

PMID- 20811617
TI  - Cellular responses to Cisplatin-induced DNA damage.
AB  - Cisplatin is one of the most effective anticancer agents widely used in the
      treatment of solid tumors. It is generally considered as a cytotoxic drug which
      kills cancer cells by damaging DNA and inhibiting DNA synthesis. How cells
      respond to cisplatin-induced DNA damage plays a critical role in deciding
      cisplatin sensitivity. Cisplatin-induced DNA damage activates various signaling
      pathways to prevent or promote cell death. This paper summarizes our current
      understandings regarding the mechanisms by which cisplatin induces cell death and
      the bases of cisplatin resistance. We have discussed various steps, including the
      entry of cisplatin inside cells, DNA repair, drug detoxification, DNA damage
      response, and regulation of cisplatin-induced apoptosis by protein kinases. An
      understanding of how various signaling pathways regulate cisplatin-induced cell
      death should aid in the development of more effective therapeutic strategies for
      the treatment of cancer.

PMID- 20811620
TI  - Diffusion-driven looping provides a consistent framework for chromatin
      organization.
AB  - Chromatin folding inside the interphase nucleus of eukaryotic cells is done on
      multiple scales of length and time. Despite recent progress in understanding the
      folding motifs of chromatin, the higher-order structure still remains elusive.
      Various experimental studies reveal a tight connection between genome folding and
      function. Chromosomes fold into a confined subspace of the nucleus and form
      distinct territories. Chromatin looping seems to play a dominant role both in
      transcriptional regulation as well as in chromatin organization and has been
      assumed to be mediated by long-range interactions in many polymer models.
      However, it remains a crucial question which mechanisms are necessary to make two
      chromatin regions become co-located, i.e. have them in spatial proximity. We
      demonstrate that the formation of loops can be accomplished solely on the basis
      of diffusional motion. The probabilistic nature of temporary contacts mimics the
      effects of proteins, e.g. transcription factors, in the solvent. We establish
      testable quantitative predictions by deriving scale-independent measures for
      comparison to experimental data. In this Dynamic Loop (DL) model, the co
      localization probability of distant elements is strongly increased compared to
      linear non-looping chains. The model correctly describes folding into a confined
      space as well as the experimentally observed cell-to-cell variation. Most
      importantly, at biological densities, model chromosomes occupy distinct
      territories showing less inter-chromosomal contacts than linear chains. Thus,
      dynamic diffusion-based looping, i.e. gene co-localization, provides a consistent
      framework for chromatin organization in eukaryotic interphase nuclei.

PMID- 20811621
TI  - Bilateral renal agenesis/hypoplasia/dysplasia (BRAHD): postmortem analysis of 45
      cases with breakpoint mapping of two de novo translocations.
AB  - BACKGROUND: Bilateral renal agenesis/hypoplasia/dysplasia (BRAHD) is a relatively
      common, lethal malformation in humans. Established clinical risk factors include
      maternal insulin dependent diabetes mellitus and male sex of the fetus. In the
      majority of cases, no specific etiology can be established, although teratogenic,
      syndromal and single gene causes can be assigned to some cases.
      METHODOLOGY/PRINCIPAL FINDINGS: 45 unrelated fetuses, stillbirths or infants with
      lethal BRAHD were ascertained through a single regional paediatric pathology
      service (male:female 34:11 or 3.1:1). The previously reported phenotypic overlaps
      with VACTERL, caudal dysgenesis, hemifacial microsomia and Mullerian defects were
      confirmed. A new finding is that 16/45 (35.6%; m:f 13:3 or 4.3:1) BRAHD cases had
      one or more extrarenal malformations indicative of a disoder of laterality
      determination including; incomplete lobulation of right lung (seven cases),
      malrotation of the gut (seven cases) and persistence of the left superior vena
      cava (five cases). One such case with multiple laterality defects and sirelomelia
      was found to have a de novo apparently balanced reciprocal translocation
      46,XY,t(2;6)(p22.3;q12). Translocation breakpoint mapping was performed by
      interphase fluorescent in-situ hybridization (FISH) using nuclei extracted from
      archival tissue sections in both this case and an isolated bilateral renal
      agenesis case associated with a de novo 46,XY,t(1;2)(q41;p25.3). Both t(2;6)
      breakpoints mapped to gene-free regions with no strong evidence of cis-regulatory
      potential. Ten genes localized within 500 kb of the t(1;2) breakpoints.
      Wholemount in-situ expression analyses of the mouse orthologs of these genes in
      embryonic mouse kidneys showed strong expression of Esrrg, encoding a nuclear
      steroid hormone receptor. Immunohistochemical analysis showed that Esrrg was
      restricted to proximal ductal tissue within the embryonic kidney.
      CONCLUSIONS/SIGNIFICANCE: The previously unreported association of BRAHD with
      laterality defects suggests that renal agenesis may share a common etiology with
      heterotaxy in some cases. Translocation breakpoint mapping identified ESRRG as a
      plausible candidate gene for BRAHD.

PMID- 20811622
TI  - "When I was circumcised I was taught certain things": risk compensation and
      protective sexual behavior among circumcised men in Kisumu, Kenya.
AB  - BACKGROUND: Male circumcision has been shown to reduce the transmission of HIV
      from women to men through vaginal sex by approximately 60%. There is concern that
      men may engage in risk compensation after becoming circumcised, diminishing the
      benefits of male circumcision. METHODS AND FINDINGS: We conducted qualitative
      interviews with 30 sexually active circumcised men in Kisumu, Kenya from March to
      November 2008. Most respondents reported no behavior change or increasing
      protective sexual behaviors including increasing condom use and reducing the
      number of sexual partners. A minority of men reported engaging in higher risk
      behaviors either not using condoms or increasing the number of sex partners.
      Circumcised respondents described being able to perform more rounds of sex,
      easier condom use, and fewer cuts on the penis during sex. CONCLUSIONS: Results
      illustrate that information about MC's protection against HIV has disseminated
      into the larger community and MC accompanied by counseling and HIV testing can
      foster positive behavior change and maintain sexual behavior.

PMID- 20811623
TI  - Plasma heme oxygenase-1 concentration is elevated in individuals with type 2
      diabetes mellitus.
AB  - BACKGROUND: Circulating concentrations of heme oxygenase-1 (HO-1) have been
      recently reported to be elevated in several chronic disorders. However, no study
      has ever examined the association between circulating HO-1 concentrations and
      type 2 diabetes mellitus (T2DM). METHODS AND FINDINGS: 581 cases with newly
      diagnosed T2DM (New-T2DM) and 611 comparison controls were recruited in this two
      phase case-control study, comprising 420 cases and 429 controls collected in the
      first phase study and 161 cases and 182 controls in the second phase replication
      study. Analyses, using both separated data and combined data from the two-phase
      studies, show that plasma HO-1 concentrations were significantly increased in New
      T2DM cases compared to controls (P<0.001). Plasma HO-1 concentrations were
      significantly correlated with plasma glucose concentrations, HOMA-beta and HOMA
      IR (P<0.001). After adjustment for age, sex, BMI and family history of diabetes,
      the ORs for New-T2DM in the highest quartile of plasma HO-1 concentrations,
      compared with the lowest, was 8.23 (95% CI 5.55-12.21; P for trend <0.001). The
      trend remained significant after additional adjustment for fasting plasma
      glucose/insulin, HOMA-beta/HOMA-IR, TC/TG, smoking, drinking and history of
      hypertension, and even in further stratification analysis by age, sex, BMI,
      smoking, drinking and history of hypertension. CONCLUSIONS: Elevated plasma HO-1
      concentrations are associated with higher ORs for New-T2DM, which add more
      knowledge regarding the important role of oxidative stress in T2DM. More
      consequent studies were warranted to confirm the clinical utility of plasma HO-1,
      especially in diagnosis and prognosis of T2DM and its complications.

PMID- 20811624
TI  - Lying about the valence of affective pictures: an fMRI study.
AB  - The neural correlates of lying about affective information were studied using a
      functional magnetic resonance imaging (fMRI) methodology. Specifically, 13
      healthy right-handed Chinese men were instructed to lie about the valence,
      positive or negative, of pictures selected from the International Affective
      Picture System (IAPS) while their brain activity was scanned by a 3T Philip
      Achieva scanner. The key finding is that the neural activity associated with
      deception is valence-related. Comparing to telling the truth, deception about the
      valence of the affectively positive pictures was associated with activity in the
      inferior frontal, cingulate, inferior parietal, precuneus, and middle temporal
      regions. Lying about the valence of the affectively negative pictures, on the
      other hand, was associated with activity in the orbital and medial frontal
      regions. While a clear valence-related effect on deception was observed, common
      neural regions were also recruited for the process of deception about the valence
      of the affective pictures. These regions included the lateral prefrontal and
      inferior parietal regions. Activity in these regions has been widely reported in
      fMRI studies on deception using affectively-neutral stimuli. The findings of this
      study reveal the effect of valence on the neural activity associated with
      deception. Furthermore, the data also help to illustrate the complexity of the
      neural mechanisms underlying deception.

PMID- 20811625
TI  - PPARalpha is essential for microparticle-induced differentiation of mouse bone
      marrow-derived endothelial progenitor cells and angiogenesis.
AB  - BACKGROUND: Bone marrow-derived endothelial progenitor cells (EPCs) are critical
      for neovascularization. We hypothesized that microparticles (MPs), small
      fragments generated from the plasma membrane, can activate angiogenic programming
      of EPCs. METHODOLOGY/PRINCIPAL FINDINGS: We studied the effects of MPs obtained
      from wild type (MPs(PPARalpha+/+)) and knock-out (MPs(PPARalpha-/-)) mice on EPC
      differentiation and angiogenesis. Bone marrow-derived cells were isolated from WT
      or KO mice and were cultured in the presence of MPs(PPARalpha+/+) or
      MPs(PPARalpha-/-) obtained from blood of mice. Only MPs(PPARalpha+/+) harboring
      PPAR(alpha) significantly increased EPC, but not monocytic, differentiation. Bone
      marrow-derived cells treated with MPs(PPARalpha+/+) displayed increased
      expression of pro-angiogenic genes and increased in vivo angiogenesis.
      MPs(PPARalpha+/+) increased capillary-like tube formation of endothelial cells
      that was associated with enhanced expressions of endothelial cell-specific
      markers. Finally, the effects of MPs(PPARalpha+/+) were mediated by NF-kappaB
      dependent mechanisms. CONCLUSIONS/SIGNIFICANCE: Our results underscore the
      obligatory role of PPARalpha carried by MPs for EPC differentiation and
      angiogenesis. PPARalpha-NF-kappaB-Akt pathways may play a pivotal stimulatory
      role for neovascularization, which may, at least in part, be mediated by bone
      marrow-derived EPCs. Improvement of EPC differentiation may represent a useful
      strategy during reparative neovascularization.

PMID- 20811627
TI  - Racial differences in genetic and environmental risk to preterm birth.
AB  - Preterm birth is more prevalent in African Americans than European Americans and
      contributes to 3.4 times more African American infant deaths. Models of social
      inequity do not appreciably account for this marked disparity and molecular
      genetic studies have yet to characterize whether allelic differences that exist
      between races contribute to this gap. In this study, biometrical genetic models
      are applied to a large mixed-race sample consisting of 733,339 births to measure
      the extent that heritable factors and environmental exposures predict the timing
      of birth and explain differences between racial groups. Although we expected
      significant differences in mean gestational age between racial groups, we did not
      anticipate the variance of gestational age in African Americans (sigma(2) =
      7.097) to be nearly twice that of European Americans (sigma(2) = 3.764). Our
      results show that this difference in the variance of gestational age can largely
      be attributed to environmental sources; which were 3.1 times greater in African
      Americans. Specifically, environmental factors that change between pregnancies,
      versus exposures that influence all pregnancies within a family, are largely
      responsible for the increased reproductive heterogeneity observed in African
      American mothers. Although the contribution of both fetal and maternal genetic
      factors differed between race categories, genetic studies may best be directed to
      understanding the differences in the socio-cultural sources of this
      heterogeneity, and their possible interaction with genetic differences within and
      between races. This study provides a comprehensive description of the relative
      genetic and environmental contributions to racial differences in gestational age.

PMID- 20811626
TI  - Genetic variants in inflammation-related genes are associated with radiation
      induced toxicity following treatment for non-small cell lung cancer.
AB  - Treatment of non-small cell lung cancer (NSCLC) with radiotherapy or
      chemoradiotherapy is often accompanied by the development of esophagitis and
      pneumonitis. Identifying patients who might be at increased risk for normal
      tissue toxicity would help in determination of the optimal radiation dose to
      avoid these events. We profiled 59 single nucleotide polymorphisms (SNPs) from 37
      inflammation-related genes in 173 NSCLC patients with stage IIIA/IIIB (dry)
      disease who were treated with definitive radiation or chemoradiation. For
      esophagitis risk, nine SNPs were associated with a 1.5- to 4-fold increase in
      risk, including three PTGS2 (COX2) variants: rs20417 (HR:1.93, 95% CI:1.10-3.39),
      rs5275 (HR:1.58, 95% CI:1.09-2.27), and rs689470 (HR:3.38, 95% CI:1.09-10.49).
      Significantly increased risk of pneumonitis was observed for patients with
      genetic variation in the proinflammatory genes IL1A, IL8, TNF, TNFRSF1B, and MIF.
      In contrast, NOS3:rs1799983 displayed a protective effect with a 45% reduction in
      pneumonitis risk (HR:0.55, 95% CI:0.31-0.96). Pneumonitis risk was also modulated
      by polymorphisms in anti-inflammatory genes, including genetic variation in IL13.
      rs20541 and rs180925 each resulted in increased risk (HR:2.95, 95% CI:1.14-7.63
      and HR:3.23, 95% CI:1.03-10.18, respectively). The cumulative effect of these
      SNPs on risk was dose-dependent, as evidenced by a significantly increased risk
      of either toxicity with an increasing number of risk genotypes (P<0.001). These
      results suggest that genetic variations among inflammation pathway genes may
      modulate the development of radiation-induced toxicity and, ultimately, help in
      identifying patients who are at an increased likelihood for such events.

PMID- 20811628
TI  - Mutational characterization of the bile acid receptor TGR5 in primary sclerosing
      cholangitis.
AB  - BACKGROUND: TGR5, the G protein-coupled bile acid receptor 1 (GPBAR1), has been
      linked to inflammatory pathways as well as bile homeostasis, and could therefore
      be involved in primary sclerosing cholangitis (PSC) a chronic inflammatory bile
      duct disease. We aimed to extensively investigate TGR5 sequence variation in PSC,
      as well as functionally characterize detected variants. METHODOLOGY/PRINCIPAL
      FINDINGS: Complete resequencing of TGR5 was performed in 267 PSC patients and 274
      healthy controls. Six nonsynonymous mutations were identified in addition to 16
      other novel single-nucleotide polymorphisms. To investigate the impact from the
      nonsynonymous variants on TGR5, we created a receptor model, and introduced
      mutated TGR5 constructs into human epithelial cell lines. By using confocal
      microscopy, flow cytometry and a cAMP-sensitive luciferase assay, five of the
      nonsynonymous mutations (W83R, V178M, A217P, S272G and Q296X) were found to
      reduce or abolish TGR5 function. Fine-mapping of the previously reported PSC and
      UC associated locus at chromosome 2q35 in large patient panels revealed an
      overall association between the TGR5 single-nucleotide polymorphism rs11554825
      and PSC (odds ratio = 1.14, 95% confidence interval: 1.03-1.26, p = 0.010) and UC
      (odds ratio = 1.19, 95% confidence interval 1.11-1.27, p = 8.5 x 10(-7)), but
      strong linkage disequilibrium precluded demarcation of TGR5 from neighboring
      genes. CONCLUSIONS/SIGNIFICANCE: Resequencing of TGR5 along with functional
      investigations of novel variants provided unique insight into an important
      candidate gene for several inflammatory and metabolic conditions. While
      significant TGR5 associations were detected in both UC and PSC, further studies
      are needed to conclusively define the role of TGR5 variation in these diseases.

PMID- 20811629
TI  - Rac activation by the T-cell receptor inhibits T cell migration.
AB  - BACKGROUND: T cell migration is essential for immune responses and inflammation.
      Activation of the T-cell receptor (TCR) triggers a migration stop signal to
      facilitate interaction with antigen-presenting cells and cell retention at
      inflammatory sites, but the mechanisms responsible for this effect are not known.
      METHODOLOGY/PRINCIPAL FINDINGS: Migrating T cells are polarized with a
      lamellipodium at the front and uropod at the rear. Here we show that transient
      TCR activation induces prolonged inhibition of T-cell migration. TCR pre
      activation leads to cells with multiple lamellipodia and lacking a uropod even
      after removal of the TCR signal. A similar phenotype is induced by expression of
      constitutively active Rac1, and TCR signaling activates Rac1. TCR signaling acts
      via Rac to reduce phosphorylation of ezrin/radixin/moesin proteins, which are
      required for uropod formation, and to increase stathmin phosphorylation, which
      regulates microtubule stability. T cell polarity and migration is partially
      restored by inhibiting Rac or by expressing constitutively active moesin.
      CONCLUSIONS/SIGNIFICANCE: We propose that transient TCR signaling induces
      sustained inhibition of T cell migration via Rac1, increased stathmin
      phosphorylation and reduced ERM phosphorylation which act together to inhibit T
      cell migratory polarity.

PMID- 20811630
TI  - Insights into the binding of Phenyltiocarbamide (PTC) agonist to its target human
      TAS2R38 bitter receptor.
AB  - Humans' bitter taste perception is mediated by the hTAS2R subfamily of the G
      protein-coupled membrane receptors (GPCRs). Structural information on these
      receptors is currently limited. Here we identify residues involved in the binding
      of phenylthiocarbamide (PTC) and in receptor activation in one of the most widely
      studied hTAS2Rs (hTAS2R38) by means of structural bioinformatics and molecular
      docking. The predictions are validated by site-directed mutagenesis experiments
      that involve specific residues located in the putative binding site and trans
      membrane (TM) helices 6 and 7 putatively involved in receptor activation. Based
      on our measurements, we suggest that (i) residue N103 participates actively in
      PTC binding, in line with previous computational studies. (ii) W99, M100 and S259
      contribute to define the size and shape of the binding cavity. (iii) W99 and
      M100, along with F255 and V296, play a key role for receptor activation,
      providing insights on bitter taste receptor activation not emerging from the
      previously reported computational models.

PMID- 20811631
TI  - Modeling core metabolism in cancer cells: surveying the topology underlying the
      Warburg effect.
AB  - BACKGROUND: Alterations on glucose consumption and biosynthetic activity of amino
      acids, lipids and nucleotides are metabolic changes for sustaining cell
      proliferation in cancer cells. Irrevocable evidence of this fact is the Warburg
      effect which establishes that cancer cells prefers glycolysis over oxidative
      phosphorylation to generate ATP. Regulatory action over metabolic enzymes has
      opened a new window for designing more effective anti-cancer treatments. This
      enterprise is not trivial and the development of computational models that
      contribute to identifying potential enzymes for breaking the robustness of cancer
      cells is a priority. METHODOLOGY/PRINCIPAL FINDINGS: This work presents a
      constraint-base modeling of the most experimentally studied metabolic pathways
      supporting cancer cells: glycolysis, TCA cycle, pentose phosphate, glutaminolysis
      and oxidative phosphorylation. To evaluate its predictive capacities, a growth
      kinetics study for Hela cell lines was accomplished and qualitatively compared
      with in silico predictions. Furthermore, based on pure computational criteria, we
      concluded that a set of enzymes (such as lactate dehydrogenase and pyruvate
      dehydrogenase) perform a pivotal role in cancer cell growth, findings supported
      by an experimental counterpart. CONCLUSIONS/SIGNIFICANCE: Alterations on
      metabolic activity are crucial to initiate and sustain cancer phenotype. In this
      work, we analyzed the phenotype capacities emerged from a constructed metabolic
      network conformed by the most experimentally studied pathways sustaining cancer
      cell growth. Remarkably, in silico model was able to resemble the physiological
      conditions in cancer cells and successfully identified some enzymes currently
      studied by its therapeutic effect. Overall, we supplied evidence that constraint
      based modeling constitutes a promising computational platform to: 1) integrate
      high throughput technology and establish a crosstalk between experimental
      validation and in silico prediction in cancer cell phenotype; 2) explore the
      fundamental metabolic mechanism that confers robustness in cancer; and 3) suggest
      new metabolic targets for anticancer treatments. All these issues being central
      to explore cancer cell metabolism from a systems biology perspective.

PMID- 20811632
TI  - Distinct patterns of DNA damage response and apoptosis correlate with Jak/Stat
      and PI3kinase response profiles in human acute myelogenous leukemia.
AB  - BACKGROUND: Single cell network profiling (SCNP) utilizing flow cytometry
      measures alterations in intracellular signaling responses. Here SCNP was used to
      characterize Acute Myeloid Leukemia (AML) disease subtypes based on survival, DNA
      damage response and apoptosis pathways. METHODOLOGY AND PRINCIPAL FINDINGS:
      Thirty four diagnostic non-M3 AML samples from patients with known clinical
      outcome were treated with a panel of myeloid growth factors and cytokines, as
      well as with apoptosis-inducing agents. Analysis of induced Jak/Stat and PI3K
      pathway responses in blasts from individual patient samples identified subgroups
      with distinct signaling profiles that were not seen in the absence of a
      modulator. In vitro exposure of patient samples to etoposide, a DNA damaging
      agent, revealed three distinct "DNA damage response (DDR)/apoptosis" profiles: 1)
      AML blasts with a defective DDR and failure to undergo apoptosis; 2) AML blasts
      with proficient DDR and failure to undergo apoptosis; 3) AML blasts with
      proficiency in both DDR and apoptosis pathways. Notably, AML samples from
      clinical responders fell within the "DDR/apoptosis" proficient profile and, as
      well, had low PI3K and Jak/Stat signaling responses. In contrast, samples from
      clinical non responders had variable signaling profiles often with in vitro
      apoptotic failure and elevated PI3K pathway activity. Individual patient samples
      often harbored multiple, distinct, leukemia-associated cell populations
      identifiable by their surface marker expression, functional performance of
      signaling pathway in the face of cytokine or growth factor stimulation, as well
      as their response to apoptosis-inducing agents. CONCLUSIONS AND SIGNIFICANCE:
      Characterizing and tracking changes in intracellular pathway profiles in cell
      subpopulations both at baseline and under therapeutic pressure will likely have
      important clinical applications, potentially informing the selection of
      beneficial targeted agents, used either alone or in combination with
      chemotherapy.

PMID- 20811633
TI  - Levels of polychlorinated biphenyls (PCBs) and three organochlorine pesticides in
      fish from the Aleutian Islands of Alaska.
AB  - BACKGROUND: Persistent organic pollutants (POPs), including polychlorinated
      biphenyls (PCBs) and chlorinated pesticides, have been shown to have many adverse
      human health effects. These contaminants therefore may pose a risk to Alaska
      Natives that follow a traditional diet high in marine mammals and fish, in which
      POPs bioaccumulate. METHODS AND FINDINGS: This study examined the levels of PCBs
      and three pesticides [p, p'-DDE, mirex, and hexachlorobenzene (HCB)] in muscle
      tissue from nine fish species from several locations around the Aleutian Islands
      of Alaska. The highest median PCB level was found in rock sole (Lepidopsetta
      bilineata, 285 ppb, wet weight), while the lowest level was found in rock
      greenling (Hexagrammos lagocephalus, 104 ppb, wet weight). Lipid adjusted PCB
      values were also calculated and significant interspecies differences were found.
      Again, rock sole had the highest level (68,536 ppb, lipid weight). Concerning the
      PCB congener patterns, the more highly chlorinated congeners were most common as
      would be expected due to their greater persistence. Among the pesticides, p, p'
      DDE generally dominated, and the highest level was found in sockeye salmon
      (Oncorhynchus nerka, 6.9 ppb, wet weight). The methodology developed by U.S.
      Environmental Protection Agency (USEPA) was used to calculate risk-based
      consumption limits for the analyzed fish species. For cancer health endpoints for
      PCBs, all species would trigger strict advisories of between two and six meals
      per year, depending upon species. For noncancer effects by PCBs, advisories of
      between seven and twenty-two meals per year were triggered. None of the
      pesticides triggered consumption limits. CONCLUSION: The fish analyzed, mainly
      from Adak, contain significant concentrations of POPs, in particular PCBs, which
      raises the question whether these fish are safe to eat, particularly for
      sensitive populations. However when assessing any risk of the traditional diet,
      one must also consider the many health and cultural benefits from eating fish.

PMID- 20811634
TI  - Mouse gestation length is genetically determined.
AB  - BACKGROUND: Preterm birth is an enormous public health problem, affecting over
      12% of live births and costing over $26 billion in the United States alone. The
      causes are complex, but twin studies support the role of genetics in determining
      gestation length. Despite widespread use of the mouse in studies of the genetics
      of preterm birth, there have been few studies that actually address the precise
      natural gestation length of the mouse, and to what degree the timing of labor and
      birth is genetically determined. METHODOLOGY/PRINCIPAL FINDINGS: To further
      develop the mouse as a genetic model of preterm birth, we developed a high
      throughput monitoring system and measured the gestation length in 15 inbred
      strains. Our results show an unexpectedly wide variation in overall gestation
      length between strains that approaches two full days, while intra-strain
      variation is quite low. Although litter size shows a strong inverse correlation
      with gestation length, genetic difference alone accounts for a significant
      portion of the variation. In addition, ovarian transplant experiments support a
      primary role of maternal genetics in the determination of gestation length.
      Preliminary analysis of gestation length in the C57BL/6J-Chr#(A/J)/NaJ chromosome
      substitution strain (B.A CSS) panel suggests complex genetic control of gestation
      length. CONCLUSIONS/SIGNIFICANCE: Together, these data support the role of
      genetics in regulating gestation length and present the mouse as an important
      tool for the discovery of genes governing preterm birth.

PMID- 20811635
TI  - Identification of novel inhibitors of dietary lipid absorption using zebrafish.
AB  - Pharmacological inhibition of dietary lipid absorption induces favorable changes
      in serum lipoprotein levels in patients that are at risk for cardiovascular
      disease and is considered an adjuvant or alternative treatment with HMG-CoA
      reductase inhibitors (statins). Here we demonstrate the feasibility of
      identifying novel inhibitors of intestinal lipid absorption using the zebrafish
      system. A pilot screen of an unbiased chemical library identified novel compounds
      that inhibited processing of fluorescent lipid analogues in live zebrafish
      larvae. Secondary assays identified those compounds suitable for testing in
      mammals and provided insight into mechanism of action, which for several
      compounds could be distinguished from ezetimibe, a drug used to inhibit
      cholesterol absorption in humans that broadly inhibited lipid absorption in
      zebrafish larvae. These findings support the utility of zebrafish screening
      assays to identify novel compounds that target complex physiological processes.

PMID- 20811636
TI  - The protein network surrounding the human telomere repeat binding factors TRF1,
      TRF2, and POT1.
AB  - Telomere integrity (including telomere length and capping) is critical in overall
      genomic stability. Telomere repeat binding factors and their associated proteins
      play vital roles in telomere length regulation and end protection. In this study,
      we explore the protein network surrounding telomere repeat binding factors, TRF1,
      TRF2, and POT1 using dual-tag affinity purification in combination with
      multidimensional protein identification technology liquid chromatography--tandem
      mass spectrometry (MudPIT LC-MS/MS). After control subtraction and data
      filtering, we found that TRF2 and POT1 co-purified all six members of the
      telomere protein complex, while TRF1 identified five of six components at
      frequencies that lend evidence towards the currently accepted telomere
      architecture. Many of the known TRF1 or TRF2 interacting proteins were also
      identified. Moreover, putative associating partners identified for each of the
      three core components fell into functional categories such as DNA damage repair,
      ubiquitination, chromosome cohesion, chromatin modification/remodeling, DNA
      replication, cell cycle and transcription regulation, nucleotide metabolism, RNA
      processing, and nuclear transport. These putative protein-protein associations
      may participate in different biological processes at telomeres or, intriguingly,
      outside telomeres.

PMID- 20811637
TI  - Rapid identification of genetic modifications in Bacillus anthracis using whole
      genome draft sequences generated by 454 pyrosequencing.
AB  - BACKGROUND: The anthrax letter attacks of 2001 highlighted the need for rapid
      identification of biothreat agents not only for epidemiological surveillance of
      the intentional outbreak but also for implementing appropriate countermeasures,
      such as antibiotic treatment, in a timely manner to prevent further casualties.
      It is clear from the 2001 cases that survival may be markedly improved by
      administration of antimicrobial therapy during the early symptomatic phase of the
      illness; i.e., within 3 days of appearance of symptoms. Microbiological detection
      methods are feasible only for organisms that can be cultured in vitro and cannot
      detect all genetic modifications with the exception of antibiotic resistance.
      Currently available immuno or nucleic acid-based rapid detection assays utilize
      known, organism-specific proteins or genomic DNA signatures respectively. Hence,
      these assays lack the ability to detect novel natural variations or intentional
      genetic modifications that circumvent the targets of the detection assays or in
      the case of a biological attack using an antibiotic resistant or virulence
      enhanced Bacillus anthracis, to advise on therapeutic treatments.
      METHODOLOGY/PRINCIPAL FINDINGS: We show here that the Roche 454-based
      pyrosequencing can generate whole genome draft sequences of deep and broad enough
      coverage of a bacterial genome in less than 24 hours. Furthermore, using the
      unfinished draft sequences, we demonstrate that unbiased identification of known
      as well as heretofore-unreported genetic modifications that include indels and
      single nucleotide polymorphisms conferring antibiotic and phage resistances is
      feasible within the next 12 hours. CONCLUSIONS/SIGNIFICANCE: Second generation
      sequencing technologies have paved the way for sequence-based rapid
      identification of both known and previously undocumented genetic modifications in
      cultured, conventional and newly emerging biothreat agents. Our findings have
      significant implications in the context of whole genome sequencing-based routine
      clinical diagnostics as well as epidemiological surveillance of natural disease
      outbreaks caused by bacterial and viral agents.

PMID- 20811638
TI  - Quantitative, architectural analysis of immune cell subsets in tumor-draining
      lymph nodes from breast cancer patients and healthy lymph nodes.
AB  - BACKGROUND: To date, pathological examination of specimens remains largely
      qualitative. Quantitative measures of tissue spatial features are generally not
      captured. To gain additional mechanistic and prognostic insights, a need for
      quantitative architectural analysis arises in studying immune cell-cancer
      interactions within the tumor microenvironment and tumor-draining lymph nodes
      (TDLNs). METHODOLOGY/PRINCIPAL FINDINGS: We present a novel, quantitative image
      analysis approach incorporating 1) multi-color tissue staining, 2) high
      resolution, automated whole-section imaging, 3) custom image analysis software
      that identifies cell types and locations, and 4) spatial statistical analysis. As
      a proof of concept, we applied this approach to study the architectural patterns
      of T and B cells within tumor-draining lymph nodes from breast cancer patients
      versus healthy lymph nodes. We found that the spatial grouping patterns of T and
      B cells differed between healthy and breast cancer lymph nodes, and this could be
      attributed to the lack of B cell localization in the extrafollicular region of
      the TDLNs. CONCLUSIONS/SIGNIFICANCE: Our integrative approach has made
      quantitative analysis of complex visual data possible. Our results highlight
      spatial alterations of immune cells within lymph nodes from breast cancer
      patients as an independent variable from numerical changes. This opens up new
      areas of investigations in research and medicine. Future application of this
      approach will lead to a better understanding of immune changes in the tumor
      microenvironment and TDLNs, and how they affect clinical outcomes.

PMID- 20811640
TI  - Antimalarial exposure delays Plasmodium falciparum intra-erythrocytic cycle and
      drives drug transporter genes expression.
AB  - BACKGROUND: Multi-drug resistant Plasmodium falciparum is a major obstacle to
      malaria control and is emerging as a complex phenomenon. Mechanisms of drug
      evasion based on the intracellular extrusion of the drug and/or modification of
      target proteins have been described. However, cellular mechanisms related with
      metabolic activity have also been seen in eukaryotic systems, e.g. cancer cells.
      Recent observations suggest that such mechanism may occur in P. falciparum.
      METHODOLOGY/PRINCIPAL FINDINGS: We therefore investigated the effect of
      mefloquine exposure on the cell cycle of three P. falciparum clones (3D7, FCB,
      W2) with different drug susceptibilities, while investigating in parallel the
      expression of four genes coding for confirmed and putative drug transporters
      (pfcrt, pfmdr1, pfmrp1 and pfmrp2). Mefloquine induced a previously not described
      dose and clone dependent delay in the intra-erythrocytic cycle of the parasite.
      Drug impact on cell cycle progression and gene expression was then merged using a
      non-linear regression model to determine specific drug driven expression. This
      revealed a mild, but significant, mefloquine driven gene induction up to 1.5
      fold. CONCLUSIONS/SIGNIFICANCE: Both cell cycle delay and induced gene expression
      represent potentially important mechanisms for parasites to escape the effect of
      the antimalarial drug.

PMID- 20811639
TI  - Linkage specific fucosylation of alpha-1-antitrypsin in liver cirrhosis and
      cancer patients: implications for a biomarker of hepatocellular carcinoma.
AB  - BACKGROUND: We previously reported increased levels of protein-linked
      fucosylation with the development of liver cancer and identified many of the
      proteins containing the altered glycan structures. One such protein is alpha-1
      antitrypsin (A1AT). To advance these studies, we performed N-linked glycan
      analysis on the five major isoforms of A1AT and completed a comprehensive study
      of the glycosylation of A1AT found in healthy controls, patients with hepatitis C
      (HCV) induced liver cirrhosis, and in patients infected with HCV with a
      diagnosis of hepatocellular carcinoma (HCC). METHODOLOGY/PRINCIPAL FINDINGS:
      Patients with liver cirrhosis and liver cancer had increased levels of
      triantennary glycan-containing outer arm (alpha-1,3) fucosylation. Increases in
      core (alpha-1,6) fucosylation were observed only on A1AT from patients with
      cancer. We performed a lectin fluorophore-linked immunosorbent assay using
      Aleuria Aurantia lectin (AAL), specific for core and outer arm fucosylation in
      over 400 patients with liver disease. AAL-reactive A1AT was able to detect HCC
      with a sensitivity of 70% and a specificity of 86%, which was greater than that
      observed with the current marker of HCC, alpha-fetoprotein. Glycosylation
      analysis of the false positives was performed; results indicated that these
      patients had increases in outer arm fucosylation but not in core fucosylation,
      suggesting that core fucosylation is cancer specific. CONCLUSIONS/SIGNIFICANCE:
      This report details the stepwise change in the glycosylation of A1AT with the
      progression from liver cirrhosis to cancer and identifies core fucosylation on
      A1AT as an HCC specific modification.

PMID- 20811641
TI  - Chromosome tips damaged in anaphase inhibit cytokinesis.
AB  - Genome maintenance is ensured by a variety of biochemical sensors and pathways
      that repair accumulated damage. During mitosis, the mechanisms that sense and
      resolve DNA damage remain elusive. Studies have demonstrated that damage
      accumulated on lagging chromosomes can activate the spindle assembly checkpoint.
      However, there is little known regarding damage to DNA after anaphase onset. In
      this study, we demonstrate that laser-induced damage to chromosome tips
      (presumptive telomeres) in anaphase of Potorous tridactylis cells (PtK2) inhibits
      cytokinesis. In contrast, equivalent irradiation of non-telomeric chromosome
      regions or control irradiations in either the adjacent cytoplasm or adjacent to
      chromosome tips near the spindle midzone during anaphase caused no change in the
      eventual completion of cytokinesis. Damage to only one chromosome tip caused
      either complete absence of furrow formation, a prolonged delay in furrow
      formation, or furrow regression. When multiple chromosome tips were irradiated in
      the same cell, the cytokinesis defects increased, suggesting a potential dose
      dependent mechanism. These results suggest a mechanism in which dysfunctional
      telomeres inhibit mitotic exit.

PMID- 20811642
TI  - Changes in human Langerhans cells following intradermal injection of influenza
      virus-like particle vaccines.
AB  - There is a significant gap in our fundamental understanding of early
      morphological and migratory changes in human Langerhans cells (LCs) in response
      to vaccine stimulation. As the vast majority of LCs studies are conducted in
      small animal models, substantial interspecies variation in skin architecture and
      immunity must be considered when extrapolating the results to humans. This study
      aims to determine whether excised human skin, maintained viable in organ culture,
      provides a useful human model for measuring and understanding early immune
      response to intradermally delivered vaccine candidates. Excised human breast skin
      was maintained viable in air-liquid-interface organ culture. This model was used
      for the first time to show morphological changes in human LCs stimulated with
      influenza virus-like particle (VLP) vaccines delivered via intradermal injection.
      Immunohistochemistry of epidermal sheets and skin sections showed that LCs in VLP
      treated skin lost their typical dendritic morphology. The cells were more
      dispersed throughout the epidermis, often in close proximity to the basement
      membrane, and appeared vertically elongated. Our data provides for increased
      understanding of the complex morphological, spatial and temporal changes that
      occur to permit LC migration through the densely packed keratinocytes of the
      epidermis following exposure to vaccine. Significantly, the data not only
      supports previous animal data but also provides new and essential evidence of
      host response to this vaccination strategy in the real human skin environment.

PMID- 20811643
TI  - The RhoA GEF Syx is a target of Rnd3 and regulated via a Raf1-like ubiquitin
      related domain.
AB  - BACKGROUND: Rnd3 (RhoE) protein belongs to the unique branch of Rho family
      GTPases that has low intrinsic GTPase activity and consequently remains
      constitutively active [1], [2]. The current consensus is that Rnd1 and Rnd3
      function as important antagonists of RhoA signaling primarily by activating the
      ubiquitous p190 RhoGAP [3], but not by inhibiting the ROCK family kinases.
      METHODOLOGY/PRINCIPAL FINDINGS: Rnd3 is abundant in mouse embryonic stem (mES)
      cells and in an unbiased two-step affinity purification screen we identified a
      new Rnd3 target, termed synectin-binding RhoA exchange factor (Syx), by mass
      spectrometry. The Syx interaction with Rnd3 does not occur through the Syx DH
      domain but utilizes a region similar to the classic Raf1 Ras-binding domain
      (RBD), and most closely related to those in RGS12 and RGS14. We show that Syx
      behaves as a genuine effector of Rnd3 (and perhaps Rnd1), with binding
      characteristics similar to p190-RhoGAP. Morpholino-oligonucleotide knockdown of
      Syx in zebrafish at the one cell stage resulted in embryos with shortened
      anterior-posterior body axis: this phenotype was effectively rescued by
      introducing mouse Syx1b mRNA. A Rnd3-binding defective mutant of Syx1b mutated in
      the RBD (E164A/R165D) was more potent in rescuing the embryonic defects than wild
      type Syx1b, showing that Rnd3 negatively regulates Syx activity in vivo.
      CONCLUSIONS/SIGNIFICANCE: This study uncovers a well defined Rnd3 effector Syx
      which is widely expressed and directly impacts RhoA activation. Experiments
      conducted in vivo indicate that Rnd3 negatively regulates Syx, and that as a RhoA
      GEF it plays a key role in early embryonic cell shape changes. Thus a connection
      to signaling via the planar cell polarity pathway is suggested.

PMID- 20811644
TI  - Transcriptional regulation of human and rat hepatic lipid metabolism by the
      grapefruit flavonoid naringenin: role of PPARalpha, PPARgamma and LXRalpha.
AB  - Disruption of lipid and carbohydrate homeostasis is an important factor in the
      development of prevalent metabolic diseases such as diabetes, obesity, and
      atherosclerosis. Therefore, small molecules that could reduce insulin dependence
      and regulate dyslipidemia could have a dramatic effect on public health. The
      grapefruit flavonoid naringenin has been shown to normalize lipids in diabetes
      and hypercholesterolemia, as well as inhibit the production of HCV. Here, we
      demonstrate that naringenin regulates the activity of nuclear receptors
      PPARalpha, PPARgamma, and LXRalpha. We show it activates the ligand-binding
      domain of both PPARalpha and PPARgamma, while inhibiting LXRalpha in GAL4-fusion
      reporters. Using TR-FRET, we show that naringenin is a partial agonist of
      LXRalpha, inhibiting its association with Trap220 co-activator in the presence of
      TO901317. In addition, naringenin induces the expression of PPARalpha co
      activator, PGC1alpha. The flavonoid activates PPAR response element (PPRE) while
      suppressing LXRalpha response element (LXRE) in human hepatocytes, translating
      into the induction of PPAR-regulated fatty acid oxidation genes such as CYP4A11,
      ACOX, UCP1 and ApoAI, and inhibition of LXRalpha-regulated lipogenesis genes,
      such as FAS, ABCA1, ABCG1, and HMGR. This effect results in the induction of a
      fasted-like state in primary rat hepatocytes in which fatty acid oxidation
      increases, while cholesterol and bile acid production decreases. Our findings
      explain the myriad effects of naringenin and support its continued clinical
      development. Of note, this is the first description of a non-toxic, naturally
      occurring LXRalpha inhibitor.

PMID- 20811645
TI  - Centrally administered pertussis toxin inhibits microglia migration to the spinal
      cord and prevents dissemination of disease in an EAE mouse model.
AB  - BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) models are important
      vehicles for studying the effect of infectious elements such as Pertussis toxin
      (PTx) on disease processes related to acute demyelinating encephalomyelitis
      (ADEM) or multiple sclerosis (MS). PTx has pleotropic effects on the immune
      system. This study was designed to investigate the effects of PTx administered
      intracerebroventricularly (icv) in preventing downstream immune cell infiltration
      and demyelination of the spinal cord. METHODS AND FINDINGS: EAE was induced in
      C57BL/6 mice with MOG(35-55). PTx icv at seven days post MOG immunization
      resulted in mitigation of clinical motor symptoms, minimal T cell infiltration,
      and the marked absence of axonal loss and demyelination of the spinal cord.
      Integrity of the blood brain barrier was compromised in the brain whereas spinal
      cord BBB integrity remained intact. PTx icv markedly increased microglia numbers
      in the brain preventing their migration to the spinal cord. An in vitro transwell
      study demonstrated that PTx inhibited migration of microglia. CONCLUSION:
      Centrally administered PTx abrogated migration of microglia in EAE mice, limiting
      the inflammatory cytokine milieu to the brain and prevented dissemination of
      demyelination. The effects of PTx icv warrants further investigation and provides
      an attractive template for further study regarding the pleotropic effects of
      infectious elements such as PTx in the pathogenesis of autoimmune disorders.

PMID- 20811646
TI  - Oxygen sensing in Drosophila: multiple isoforms of the prolyl hydroxylase fatiga
      have different capacity to regulate HIFalpha/Sima.
AB  - BACKGROUND: The Hypoxia Inducible Factor (HIF) mediates cellular adaptations to
      low oxygen. Prolyl-4-hydroxylases are oxygen sensors that hydroxylate the HIF
      alpha-subunit, promoting its proteasomal degradation in normoxia. Three HIF
      prolyl hydroxylases, encoded by independent genes, PHD1, PHD2, and PHD3, occur in
      mammals. PHD2, the longest PHD isoform includes a MYND domain, whose biochemical
      function is unclear. PHD2 and PHD3 genes are induced in hypoxia to shut down HIF
      dependent transcription upon reoxygenation, while expression of PHD1 is oxygen
      independent. The physiologic significance of the diversity of the PHD oxygen
      sensors is intriguing. METHODOLOGY AND PRINCIPAL FINDINGS: We have analyzed the
      Drosophila PHD locus, fatiga, which encodes 3 isoforms, FgaA, FgaB and FgaC that
      are originated through a combination of alternative initiation of transcription
      and alternative splicing. FgaA includes a MYND domain and is homologous to PHD2,
      while FgaB and FgaC are shorter isoforms most similar to PHD3. Through a
      combination of genetic experiments in vivo and molecular analyses in cell
      culture, we show that fgaB but not fgaA is induced in hypoxia, in a Sima
      dependent manner, through a HIF-Responsive Element localized in the first intron
      of fgaA. The regulatory capacity of FgaB is stronger than that of FgaA, as
      complete reversion of fga loss-of-function phenotypes is observed upon transgenic
      expression of the former, and only partial rescue occurs after expression of the
      latter. CONCLUSIONS AND SIGNIFICANCE: Diversity of PHD isoforms is a conserved
      feature in evolution. As in mammals, there are hypoxia-inducible and non
      inducible Drosophila PHDs, and a fly isoform including a MYND domain co-exists
      with isoforms lacking this domain. Our results suggest that the isoform devoid of
      a MYND domain has stronger regulatory capacity than that including this domain.

PMID- 20811647
TI  - Hysterectomy and Bilateral Salpingoovariectomy in a Transsexual Subject without
      Visible Scaring.
AB  - Objective. To report on the use of laparoendoscopic single-site surgery (LESS)
      for the management of total hysterectomy (TH) with bilateral salpingoovariectomy
      (BSO) in a subject affected by gender identity disorder. Design. Case report.
      Setting. University Hospital. Patient(s). A 27-year-old affected by Gender
      Identity Disorder underwent a hysterectomy and BSO as part of surgical sex
      reassignment. Intervention(s). Laparoendoscopic single-site surgery access for TH
      and BSO. Main Outcome Measure(s). The procedure was performed without incident.
      The trocar placement was easy and safe, without inadvertent port removal. No
      vascular or visceral injuries, loss of pneumoperitoneum, or intraoperative port
      site bleeding occurred. Result(s). A detailed description of the technique of a
      single-site surgery for management of hysterectomy and BSO. Conclusion. Our case
      presents the first report of single-site surgery for surgical treatment of
      subjects affected by GID.

PMID- 20811648
TI  - Recent visual decline-a health hazard with consequences for social life: a study
      of home care clients in 12 countries.
AB  - Information about recent visual decline (RVD) and its consequences is limited.
      The aim was to investigate this in an observational, prospective study.
      Participants were recipients of community home services, >/=65 years, from
      Ontario (Canada, n = 101618), Finland (the-RAI-database, STAKES, n = 1103), and
      10 other European countries (the-Aged-in-HOmeCarestudy (AdHOC), n = 3793). The
      instrument RAI-HC version 2.0 was used in all sites. RVD was assessed by the item
      "Worsening of vision compared to status 90 days ago" and was present in 6-49% in
      various sites, more common among persons living alone, and in females. In the
      AdHOC sample, RVD was independently associated with declining social activity and
      limited outdoors activities due to fear of falling. The combination of stable
      vision impairment (SVI) and RVD was independently associated with IADL loss. RVD
      is common and has greater impact than SVI on social life and function. Caregivers
      should be particularly aware of RVD, its consequences, and help patients to seek
      assessments, treatment, and rehabilitation.

PMID- 20811656
TI  - D-chiro-inositol glycans in insulin signaling and insulin resistance.
AB  - Classical actions of insulin involve increased glucose uptake from the
      bloodstream and its metabolism in peripheral tissues, the most important and
      relevant effects for human health. However, nonoxidative and oxidative glucose
      disposal by activation of glycogen synthase (GS) and mitochondrial pyruvate
      dehydrogenase (PDH) remain incompletely explained by current models for insulin
      action. Since the discovery of insulin receptor Tyr kinase activity about 25
      years ago, the dominant paradigm for intracellular signaling by insulin invokes
      protein phosphorylation downstream of the receptor and its primary Tyr
      phosphorylated substrates-the insulin receptor substrate family of proteins. This
      scheme accounts for most, but not all, intracellular actions of insulin.
      Essentially forgotten is the previous literature and continuing work on second
      messengers generated in cells in response to insulin. Treatment and even
      prevention of diabetes and metabolic syndrome will benefit from a more complete
      elucidation of cellular-signaling events activated by insulin, to include the
      actions of second messengers such as glycan molecules that contain D-chiro
      inositol (DCI). The metabolism of DCI is associated with insulin sensitivity and
      resistance, supporting the concept that second messengers have a role in
      responses to and resistance to insulin.

PMID- 20811657
TI  - Diet restriction inhibits apoptosis and HMGB1 oxidation and promotes inflammatory
      cell recruitment during acetaminophen hepatotoxicity.
AB  - Acetaminophen (APAP) overdose is a major cause of acute liver failure and serves
      as a paradigm to elucidate mechanisms, predisposing factors and therapeutic
      interventions. The roles of apoptosis and inflammation during APAP hepatotoxicity
      remain controversial. We investigated whether fasting of mice for 24 h can
      inhibit APAP-induced caspase activation and apoptosis through the depletion of
      basal ATP. We also investigated in fasted mice the critical role played by
      inhibition of caspase-dependent cysteine 106 oxidation within high mobility group
      box-1 protein (HMGB1) released by ATP depletion in dying cells as a mechanism of
      immune activation. In fed mice treated with APAP, necrosis was the dominant form
      of hepatocyte death. However, apoptosis was also observed, indicated by K18
      cleavage, DNA laddering and procaspase-3 processing. In fasted mice treated with
      APAP, only necrosis was observed. Inflammatory cell recruitment as a consequence
      of hepatocyte death was observed only in fasted mice treated with APAP or fed
      mice cotreated with a caspase inhibitor. Hepatic inflammation was also associated
      with loss in detection of serum oxidized-HMGB1. A significant role of HMGB1 in
      the induction of inflammation was confirmed with an HMGB1-neutralizing antibody.
      The differential response between fasted and fed mice was a consequence of a
      significant reduction in basal hepatic ATP, which prevented caspase processing,
      rather than glutathione depletion or altered APAP metabolism. Thus, the
      inhibition of caspase-driven apoptosis and HMGB1 oxidation by ATP depletion from
      fasting promotes an inflammatory response during drug-induced
      hepatotoxicity/liver pathology.

PMID- 20811659
TI  - Nutrition in oncology: the case of micronutrients (review).
AB  - In the course of cancer disease, many oncological patients develop tumor
      associated malnutrition characterized by an insufficient supply of macro- and
      micronutrients. The inadequate nutritional status and the cancer anorexia
      cachexia syndrome related to it are clinically relevant, as the response to
      antineoplastic measures, such as radiation and chemotherapy, is diminished, their
      side effects aggravated and the patient's quality of life and prognosis
      negatively affected. Therefore, the supportive nutrition care of oncological
      patients is of central importance. In this context, vitamins, minerals and long
      chain omega -3 fatty acids are becoming more and more relevant in oncology
      although the benefit of such supplements is discussed controversially. Starting
      from a description of the etiopathogenesis and the pathophysiological
      consequences of cancer-associated malnutrition, the present study provides an
      overview of the importance of micronutrients for oncological patients. In the
      case of reduced food intake and/or inappropriate food choice the use of a multi
      vitamin-multimineral supplement administered in physiological doses, i.e.
      nutrient quantities approximately corresponding to the recommended daily
      allowances, can be generally recommended. However, to enhance postoperative wound
      healing, it seems that cancer patients require higher amounts of micronutrients
      than healthy individuals. Because vitamin D deficiency is highly prevalent in
      oncological patients, improvement of vitamin D status is of special interest.

PMID- 20811658
TI  - Genome-wide association for smoking cessation success in a trial of precessation
      nicotine replacement.
AB  - Abilities to successfully quit smoking display substantial evidence for
      heritability in classic and molecular genetic studies. Genome-wide association
      (GWA) studies have demonstrated single-nucleotide polymorphisms (SNPs) and
      haplotypes that distinguish successful quitters from individuals who were unable
      to quit smoking in clinical trial participants and in community samples. Many of
      the subjects in these clinical trial samples were aided by nicotine replacement
      therapy (NRT). We now report novel GWA results from participants in a clinical
      trial that sought dose/response relationships for "precessation" NRT. In this
      trial, 369 European-American smokers were randomized to 21 or 42 mg NRT,
      initiated 2 wks before target quit dates. Ten-week continuous smoking abstinence
      was assessed on the basis of self-reports and carbon monoxide levels. SNP
      genotyping used Affymetrix 6.0 arrays. GWA results for smoking cessation success
      provided no P value that reached "genome-wide" significance. Compared with
      chance, these results do identify (a) more clustering of nominally positive
      results within small genomic regions, (b) more overlap between these genomic
      regions and those identified in six prior successful smoking cessation GWA
      studies and (c) sets of genes that fall into gene ontology categories that appear
      to be biologically relevant. The 1,000 SNPs with the strongest associations form
      a plausible Bayesian network; no such network is formed by randomly selected sets
      of SNPs. The data provide independent support, based on individual genotyping,
      for many loci previously nominated on the basis of data from genotyping in pooled
      DNA samples. These results provide further support for the idea that aid for
      smoking cessation may be personalized on the basis of genetic predictors of
      outcome.

PMID- 20811660
TI  - Pathotropic targeting advances clinical oncology: tumor-targeted localization of
      therapeutic gene delivery.
AB  - The advent of pathotropic (disease-seeking) targeting has transported genetic
      medicine across the threshold of history with the progressive clinical validation
      of Rexin-G, a tumor-targeted nanosized anti-cancer agent. Achieving noteworthy
      single-agent efficacy and survival benefits in otherwise intractable cancers, the
      molecular biotechnology platform has stimulated intense interest in the
      underlying mechanisms-of-action. This report exhibits the effective localization
      of Rexin-G nanoparticles within a metastatic liver lesion, as observed upon its
      surgical excision.

PMID- 20811661
TI  - Irinotecan overcomes the resistance to 5-fluorouracil in human colon cancer
      xenografts by down-regulation of intratumoral thymidylate synthase.
AB  - To clarify the molecular interaction of irinotecan (CPT-11) and oxaliplatin (l
      OHP) in combination with 5-fluorouracil (5-FU), the antitumor effects of CPT-11
      and l-OHP combined with the oral 5-FU prodrug, S-1 composed by tegafur, gimeracil
      and potassium oteracil, were investigated on human colon cancer KM12C xenografts
      sensitive or resistant to 5-FU in nude mice. In parental KM12C tumor xenografts,
      combined treatment of CPT-11 with oral S-1 significantly augmented the antitumor
      activity compared with those of CPT-11 and S-1 alone. Interestingly, combined
      therapy of CPT-11 with S-1 was markedly effective with almost 90% of inhibition
      of tumor growth on 5-FU-resistant tumors (KM12C/ 5-FU), and its potency likely
      corresponded to that in parental tumors. In contrast, combined administration of
      l-OHP with S-1 did not shown an effect on KM12C/5-FU tumor xenografts. To
      investigate why only CPT-11 potentiated the anti-tumor activity in combination
      with 5-FU pro-drugs against 5-FU-resistant colon tumors, the activities or
      expression levels of thymidylate synthase (TS), ribonucleotide reductase (RNR)
      and other enzymes in 5-FU-metabolism in both tumors were measured following
      administration of CPT-11 and/or l-OHP. CPT-11, but not l-OHP, induced a decrease
      in activities and protein levels of TS and an increase in those of RNR in KM12C/5
      FU tumors only, which was likely related to decreased expressions of several
      proteins in G1/S phase of the cells including CDK4, pRB, and E2F1 in these
      tumors. These findings suggest that CPT-11, but not l-OHP, would overcome the
      resistance to 5-FU in combination with 5-FU pro-drugs on 5-FU-resistant colon
      tumors.

PMID- 20811662
TI  - Anti-tumor effect by inhibition of NF-kappaB activation using nafamostat mesilate
      for pancreatic cancer in a mouse model.
AB  - Constitutive NF-kappaB activation plays a key role in the aggressive behavior of
      pancreatic cancer. We have reported that nafamostat mesilate, a serine-protease
      inhibitor, inhibited NF-kappaB activation and induced apoptosis in human
      pancreatic cancer cells. The aim of this study is to evaluate the therapeutic
      efficacy of nafamostat mesilate against pancreatic cancer. In vitro, nafamostat
      mesilate inhibited NF-kappaB activation of human pancreatic cancer cell line
      (Panc-1) by suppressing IkappaBalpha phosphorylation and induced caspase-8
      mediated apoptosis. In vivo, Panc-1 was implanted into the back of nude mice.
      Five weeks after implantation, nafamostat mesilate was injected intraperitoneally
      as the treatment group (n=11) three times a week for six weeks, while the control
      group (n=13) received vehicle only. At the end of six-week treatment, the tumors
      grew up to 12.89+/-4.27 mm (mean +/- SD) in the treatment group, and 17.93+/-4.45
      mm in the control group, respectively. The tumor volume and weight of the
      treatment group were reduced by 43 and 61% as compared with the control group.
      The tumor growth was significantly inhibited in the treatment group (p<0.0001).
      Assays of primary tumors also indicated that nafamostat mesilate inhibited NF
      kappaB activation by suppressing IkappaBalpha phosphorylation, resulting in
      caspase-8 mediated apoptosis. These results suggested that nafamostat mesilate
      has anti-neoplastic property against experimental pancreatic cancer.

PMID- 20811663
TI  - p53 mutation, but not in vitro predictor genes of therapeutic efficacy of
      cisplatin, is clinically relevant in comparing partial and complete responder
      cases of maxillary squamous cell carcinoma.
AB  - To predict the efficacy of cisplatin and radiation therapy for maxillary squamous
      cell carcinoma, we examined the mRNA expression of 14 cisplatin-resistant genes
      and p53 mutation in specimens biopsied from patients prior to initiation of
      therapy. Five of 10 patients had mutations in the p53 gene, of whom four had
      residual tumors pathologically following chemoradiotherapy (p=0.0476). Of 14
      genes examined, the mRNA expression of ATP7B was significantly lower in cases
      that were resistant to chemoradiotherapy. Six genes including multidrug
      resistance protein 1 (MDR-1), multidrug resistance associated protein 1 (MRP-1),
      Cu++ transporting, beta polypeptide (ATP7B), xeroderma pigmentosum,
      complementation group A (XPA), excision repair cross-complementing rodent repair
      deficiency, complementation group 1 (ERCC-1) and B-cell CLL/lymphoma 2 (BCL2)
      were down-regulated in cases of recurrent cancers. These results show that the
      evaluation of p53 mutation provides the most useful predictor of therapeutic
      effects. In responder cases, the drug-resistant genes that were determined in
      cell lines by culture do not necessarily translate into clinical relevance.

PMID- 20811664
TI  - A new approach to concordance in mid-infrared spectromicroscopy mapping of
      malignant tumors.
AB  - Mid-infrared spectromicroscopy studies on biological tissue sections require
      accurate identification of tumor-bearing areas in histology-stained and infrared
      unstained tissue sections. Concordance was achieved as follows: paired stained
      and unstained thin (5 microm) human brain tumor cryosections mounted on slides
      were scanned with a Nikon Coolscan 4000 film scanner at 4000 dpi, edited with
      Adobe Photoshop CS2 software, and both digital images saved. A digital tractile
      grid, developed in our laboratory, was overlaid onto both images. Boundaries of
      tumor-containing areas in stained sections were identified by light microscopy,
      and a digital boundary map constructed. The map was transferred onto the
      unstained spectromicroscopy tissue image, and finally layered onto the gridded,
      equisized, spectromicroscope-generated overview image prior to Fourier transform
      infrared spectromicroscopy. Accurate identification of tumor-bearing areas,
      normal brain tissue and transitional zones allowed for meaningful interpretation
      of respective spectral patterns in detecting subtle differences within
      biochemical profiles. This is the first reported method of a standardized
      technique for ensuring concordance in mapping of malignant tumors by mid-infrared
      spectromicroscopy. This technique is applicable to all biological thin tissue
      sections, and serves to enhance accuracy of concordance between globar- and
      synchrotron-light generated infrared data with that obtained by conventional
      light microscopy.

PMID- 20811665
TI  - CD98 expression is associated with the grade of malignancy in thymic epithelial
      tumors.
AB  - CD98 has been associated with tumor growth and is highly expressed in human
      neoplasms. The aim of this study was to evaluate the clinicopathological
      significance of CD98 expression in thymic epithelial tumors. Forty-nine patients
      with thymic epithelial tumors were included in this study. Tumor sections were
      stained by immunohistochemistry for CD98; vascular endothelial growth factor
      (VEGF); micro-vessels (CD31 and CD34); cell cycle control marker (p53); and
      apoptosis marker (Bcl-2). CD98 expression for low-risk thymomas, high-risk
      thymomas, and thymic carcinomas were 1 (4%) of 27, 9 (82%) of 11, and 11 (100%)
      of 11, respectively. There was positive correlation between CD98 and VEGF
      (p<0.001), microvessel density (CD31 and CD34) (p<0.001) and p53 (p<0.001).
      However, Bcl-2 showed no positive correlation with CD98 expression. The
      expression of CD98 were also significantly associated with the grade of
      malignancy in thymic epithelial tumors. Multivariate analysis revealed that
      overexpression of CD98 was a significant independent factor predicting a poor
      outcome in thymic epithelial tumors. CD98 expression was associated with the
      grade of malignancy in thymic epithelial tumors. Moreover, CD98 expression was
      closely correlated with angiogenesis and cell cycle control, and was useful for
      predicting poor outcome.

PMID- 20811666
TI  - Increased apoptosis and decreased proliferation of colonic epithelium in dextran
      sulfate sodium-induced colitis in mice.
AB  - The pathogenic mechanisms responsible for inflammatory bowel disease, especially
      ulcerative colitis (UC), are poorly understood. In animal models, the oral
      administration of dextran sulfate sodium (DSS) induces colitis, which exhibits
      several clinical and histological features similar to UC. In addition, the
      longstanding administration of DSS also induces colon cancer. However, the
      pathogenic factors responsible for DSS-induced colitis and the subsequent colon
      cancer also remain unclear. In particular, there are only limited data concerning
      colonic epithelia cell apoptosis and proliferation in DSS-induced colitis.
      Therefore, we investigated the relationships between these factors. Colitis was
      induced in BALB/cA Jcl mice by 8 days of oral administration of standard diets
      containing 5% (w/w of diet) DSS. The control mice received the standard diets
      only. Morphological changes in the colonic mucosa were evaluated and scored by
      light microscopy. Apoptosis was studied by the TUNEL assay, and cell
      proliferation by Ki-67 immunoreactivity. The macroscopic findings showed the most
      severe inflammation in the distal colon. Epithelial apoptosis increased
      approximately 5-fold after DSS administration as compared to the controls. On the
      other hand, the mitotic cells decreased about half-fold as compared to the
      controls. Ki-67 immunohistochemistry showed that cells with cell cycle arrest at
      the G0 stage in the crypt increased approximately 2-fold as compared to the
      controls. In conclusion, the increased apoptosis and decreased proliferation
      might lead to a breakdown of the epithelial barrier function, and thus facilitate
      the mucosal invasion of intraluminal microorganisms in DSS-induced colitis.

PMID- 20811667
TI  - DNA copy number aberrations associated with aneuploidy and chromosomal
      instability in breast cancers.
AB  - Biological characteristics of a tumor are primarily affected by its genomic
      alterations. It is thus important to ascertain whether there are genomic changes
      linked with DNA ploidy and/or chromosomal instability (CIN). In the present
      study, using fresh-frozen samples of 46 invasive breast cancers, laser scanning
      cytometry, array-based comparative genomic hybridization, and chromosome
      fluorescence in situ hybridization were performed to assess DNA ploidy, DNA copy
      number aberrations (DCNAs), and CIN status. Both ploidy and CIN status were
      examined in 36 tumors, resulting in 23 aneuploid/CIN+ tumors, 1 aneuploid/CIN-, 2
      diploid/CIN+, and 10 diploid/CIN- tumors. Comparison of the aCGH data with the
      DNA ploidy and CIN status identified cytogenetically 11 characteristic breast
      cancers with distinctive DCNAs. The 11 tumors were classified into two types; one
      type is diploid/CIN- phenotype containing 4 DCNAs, and the other aneuploid/CIN+
      phenotype containing 7 DCNAs. In 30 (65.2%) of the 36 breast cancers, the status
      of DNA ploidy and CIN depended on the type of DCNAs. Furthermore, the DNA ploidy
      phenotype depended on the dominant type of DCNAs even in tumors with a mixture of
      multiple DCNAs of one type and a single DCNA of the other type. Tumors with
      multiple DCNAs of both types represented aneuploidy and over three quarters of
      breast cancers carry at least one type of the DCNAs. These results suggested
      that, in breast cancers, the status of DNA ploidy and CIN was likely to determine
      at the beginning of carcinogenesis.

PMID- 20811668
TI  - Genetic profiles distinguish different types of hereditary ovarian cancer.
AB  - Heredity represents the strongest risk factor for ovarian cancer with disease
      predisposing mutations identified in 15% of the tumors. With the aim to identify
      genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian
      cancers linked to the hereditary breast and ovarian cancer (HBOC) syndrome and
      the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide
      array comparative genomic hybridization was applied to 12 HBOC associated tumors
      with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene
      mutations with 24 sporadic ovarian cancers as a control group. Unsupervised
      cluster analysis identified two distinct subgroups related to genetic complexity.
      Sporadic and HBOC associated tumors had complex genetic profiles with an average
      41% of the genome altered, whereas the mismatch repair defective tumors had
      stable genetic profiles, with an average 18% of the genome altered. Losses of
      4q34, 13q12-q32 and 19p13 were overrepresented in the HBOC subset. Discriminating
      genes within these regions include BRCA2, FOXO1A and RB1. Gains on chromosomes 17
      and 19 characterized the HNPCC tumors, but target genes herein are unknown. The
      results indicate that HBOC and HNPCC associated ovarian cancer develop along
      distinct genetic pathways and genetic profiles can thus be applied to distinguish
      between different types of hereditary ovarian cancer.

PMID- 20811669
TI  - High-level transgene expression mediated by the piggyBac transposon enhances
      transgenic therapeutic effects in cervical cancer xenografts.
AB  - The piggyBac (PB) transposon is a recently identified, active and flexible
      transgene vector, combining the advantages of non-viral gene delivery with
      genomic integration and persistent transgene expression. In this study, we
      utilized the PB transposon to carry the herpes simplex thymidine kinase (HSV-tk)
      and red fluorescent protein (mRFP1) reporter genes into the HeLa cervical cancer
      cell line or tumor xenografts of cervical cancer. Our data showed that HSV-tk and
      mRFP1 were expressed in HeLa cells and tumor xenografts three weeks after
      intratumoral injection. The mRNA and protein levels of HSV-tk and mRFP1 were
      increased by using the PB transposon vector. Our system also demonstrated that
      sensitivity of transfected HeLa cells to the pro-drug ganciclovir (GCV) was
      enhanced in vitro and in vivo. Furthermore, our data indicated that the enhanced
      transgenic therapeutic effect was strongly associated with high-level transgene
      expression mediated by the PB transposon. Our results suggest that applying the
      PB transposon in HSV-tk gene delivery and GCV treatment is a promising gene
      therapy strategy in the treatment of cervical cancer.

PMID- 20811670
TI  - Elevated L1CAM expression in precursor lesions and primary and metastastic
      tissues of pancreatic ductal adenocarcinoma.
AB  - The promigratory molecule L1CAM is overexpressed in various tumors, often
      representing an unfavorable prognostic marker. Recently, we identified L1CAM
      expression in pancreatic ductal adenocarcinoma (PDAC) cells accounting for
      chemoresistance and increased cell migration. Thus, the present study aims at
      further elucidating the role of L1CAM in a larger cohort of PDAC specimens
      including precursor lesions and metastasis. L1CAM expression was determined by
      immunohistochemistry in tissues of 123 patients including tissues of 110 primary
      PDACs, 15 lymph node metastases and 14 liver metastases. The immunohistochemical
      analyses revealed L1CAM expression in 92.7% of primary PDACs, 80% of lymph node
      metastases and 100% of liver metastases. Furthermore, we have investigated PDAC
      precursors, pancreatic intraepithelial neoplasia (PanIN) lesions, revealing a
      significant increase of L1CAM expression with the PanIN grade (6.4 and 6.8% in
      PanIN 1A and B, 35% in PanIN 2 and 20% in PanIN 3). The elevated expression of
      L1CAM already found in PanINs points to a role of L1CAM quite early in
      tumorigenesis of PDAC. Furthermore, its broad expression in primary tumors as
      well as in metastases of PDAC patients provide a rationale to further explore the
      value of L1CAM as a therapeutic target in the treatment of this highly malignant
      tumor.

PMID- 20811671
TI  - High-throughput DNA hypermethylation profiling in different ovarian epithelial
      cancer subtypes using universal bead array.
AB  - DNA hypermethylation is common and plays a critical role in the regulation of
      gene expression. It is considered a major cause of carcinogenesis. High
      throughput profiling method has been developed to analyze the methylation status
      of hundreds of pre-selected genes simultaneously. The aim of this study was to
      analyze promoter hypermethylation profiles of each subtype of ovarian epithelial
      cancer (OEC), to improve the understanding of the role of epigenetic silencing in
      carcinogenesis. DNA hypermethylation profiles on fresh frozen tissue samples of 5
      serous, 3 mucinous, 5 endometrioid and 4 clear cell types of OEC, as well as 5
      normal ovarian tissue samples as control. We used a high-throughput method for
      analyzing the hypermethylation status of 1,505 CpG loci selected from 871 genes
      simultaneously by GoldenGate Methylation Cancer Panel I (Illumina Human-6 v2
      Expression BeadChip). Methylation status of seven genes was verified by
      methylation specific PCR (MSP). We identified 20, 37, 15 and 56 hypermethylated
      CpG locations in serous, mucinous, endometrioid and clear cell type OEC compared
      to control. Only 6 CpG loci were commonly hypermethylated across all subtypes of
      OEC. Hypermethylated loci of serous 17 (81.0%) and endometrioid type 10 (71.4%)
      were identical to that of clear cell type. However, mucinous type showed 17
      peculiar loci (43.6%) out of 39 hypermethylated loci. The unique DNA
      hypermethylation patterns identified in different OEC subtypes suggest that their
      cause may involve different epigenetic mechanisms and the Bead chip used in this
      study is a useful tool to analyze DNA hypermethylation.

PMID- 20811672
TI  - Microsatellite instability and hMLH1 and hMSH2 expression in renal tumors.
AB  - Defects in the function of mismatch repair (MMR) genes result in genetic
      instability, a common feature of malignant progression. This study was conducted
      to determine the frequency of genetic instability [defined as microsatellite
      instability (MSI)] and to evaluate the sensitivity/specificity of
      immunohistochemistry in predicting the deficiency in MMR genes in renal cortical
      tumors. A total of 51 surgically-resected renal tumors (27 clear cell, 10
      papillary, 5 chromophobe carcinomas and 9 oncocytomas) were studied. We also
      analyzed the correlation with clinicopathological parameters, the MSI status
      (assessed by using 5 microsatellite markers: D2S123, D11S904, D3S1621, D3S1683
      and BAT26), and the immunohistochemical expression of 2 major MMR genes [the
      human mutL homolog 1 (hMLH1) and the human mutS homolog 2 (hMSH2)]. Sixteen cases
      (31.4%) showed MSI: Three (5.9%) demonstrated a high level of MSI, 11 (21.6%)
      demonstrated a low level of MSI, 2 (3.9%) presented with a loss of
      heterozygosity, and the remaining 35 (68.6%) exhibited microsatellite stability.
      The loss of hMLH1 and hMSH2 immunohistochemical expressions was observed in 5/51
      (9.8%) and 9/51 (17.6%) cases, respectively. The complete absence of both hMLH1
      and hMSH2 immunohistochemical expressions was observed only in the 3 cases with a
      high level of MSI. This study showed that defects in MMR genes are involved in
      renal carcinogenesis and correlate with the occurrence of MSI.

PMID- 20811673
TI  - C4orf7 contributes to ovarian cancer metastasis by promoting cancer cell
      migration and invasion.
AB  - Gene C4orf7, renamed FDC-SP (follicular dendritic cell secreted protein, FDC-SP)
      was first isolated from human tonsils. Up to the present, the function of this
      gene was still poorly understood. In this study, we report the expression of gene
      C4orf7 in a panel of tumor types. The percentages of C4orf7 positive expression
      in the tumor patients with metastases were notably higher than those in the
      cancer without metastases. On the contrary, the expression was hardly noted in
      normal tissues and corresponding benign lesions. In vitro, the up-regulation of
      C4orf7 in ovarian cancer cell lines was associated with enhanced motility and
      invasiveness. Furthermore, the overexpression of C4orf7 resulted in Akt ser473
      phosphorylation and decreased E-cadherin expression. The role of C4orf7 in
      ovarian cancer cell morphology, motility and invasion was demonstrated.

PMID- 20811674
TI  - The antitumor and antimetastatic effects of N-trimethyl chitosan-encapsulated
      camptothecin on ovarian cancer with minimal side effects.
AB  - Lymphatic metastasis plays a critical role in ovarian cancer, indicates poor
      prognoses and correlates to the majority of cancer deaths. Camptothecin
      derivatives exhibit promising activity for the treatment of solid tumors because
      of its specific inhibition of eukaryotic DNA topoisomerase I. Yet, its
      application is hindered due to extreme water insolubility and severe side
      effects. It is essential to establish an efficient and safe protocol for the
      administration of camptothecin versus tumor metastasis and growth. In the current
      research, we encapsulated camptothecin with N-trimethyl chitosan (CPT-TMC) to
      increase its water-solubility and lower its side effects, and tested it on a high
      potential lymphogenous metastatic model of human ovarian cancer. In the prophase
      study, we successfully transfected SKOV3 cells with VEGF-D recombinant plasmid
      DNA (pcDNA3.1(+)/VEGF-D) to construct a cell line named SKOV3/VEGF-D and
      establish a feasible lymphogenous metastatic model. The antitumor and
      antimetastatic activities of CPT-TMC were evaluated in nude mice subcutaneously
      inoculated with SKOV3/VEGF-D cells at the left hindlimb claw pad. The tumor
      bearing mice were divided randomly into four groups and treated twice per week
      for three weeks. Evan's Blue Dye was used to delineate functional lymphatic
      vessels. Lymphatic metastasis rates were detected by hematoxylin and eosin (HE)
      staining. Expression of VEGF-D and MMP-9 were investigated by
      immunohistochemistry. In contrast to controls, administration of CPT-TMC achieved
      effective inhibition in primary tumor volume and lymphogenous metastasis, yet
      without apparent systemic toxic effects. These effects were associated with
      simultaneously down-regulated VEGF-D and MMP-9 expression, significantly
      decreased tumor-associated lymphatic and blood sprouts, tremendously reduced
      systemic toxic effects, dramatically increased tumor apoptotic index. Our data
      indicate that CPT-TMC is superior to CPT by maximizing its anticancer and
      antimetastatic activities with minimal toxicity on hosts. CPT-TMC may become a
      potentially therapeutic strategy against human advanced ovarian cancer.

PMID- 20811675
TI  - 14-3-3sigma expression as a prognostic marker in undifferentiated nasopharyngeal
      carcinoma.
AB  - In this study, we investigated the expression of 14-3-3sigma tumor suppressor
      gene in a panel of NPC cell lines, xenografts and primary tumors. Our objective
      was to determine the correlation between 14-3-3sigma expression and clinical
      outcome in NPC. We detected reduced 14-3-3sigma expression in 5/6 NPC tumor lines
      by quantitative RT-PCR and Western blotting. By immunohistochemical staining,
      significant down-regulation of 14-3-3sigma was also found in 26/72 (36.1%)
      primary tumors of NPC patients, who were treated with curative radiotherapy.
      Promoter methylation was confirmed in a subset of primary tumors by methylation
      specific PCR analysis. Importantly, we demonstrated that 14-3-3sigma expression
      is significantly associated with both overall survival (OS) and cancer-specific
      survival (CSS), but not with the clinical staging of NPC patients. The low 14-3
      3sigma expression was associated with improved overall (p=0.029) and cancer
      specific survival (p=0.042) on univariate analysis. 14-3-3sigma expression and
      staging were also independent variables to all the prognostic factors under
      multivariate analysis. In conclusion, low expression of 14-3-3sigma appears to be
      a valuable marker for better survival in patient with NPC. These results provide
      the evidence that 14-3-3sigma expression is a significant prognostic factor for
      NPC patients.

PMID- 20811676
TI  - Deguelin promotes apoptosis and inhibits angiogenesis of gastric cancer.
AB  - Gastric cancer is often diagnosed in locally advanced or metastatic stages, which
      preludes a poor prognosis. As only 10% of patients with advanced gastric cancer
      treated with chemotherapy survive 2 years, new approaches for preventing and
      controlling the disease are required. We therefore, assessed in gastric cancer
      cells the chemotherapeutic potential and mechanism of deguelin, a rotenoid of the
      flavonoid family isolated from several plant species. The effect of deguelin on
      the proliferation and apoptosis in the gastric cancer cells were assessed by MTT
      and flow cytometry. The growth of gastric cancer cells (SNU-484, AGS and MKN-28)
      was inhibited by deguelin in a dose-dependent manner. G2/M phase arrest was
      induced by deguelin in gastric cancer cells. deguelin (1 microM) induced
      chromatin condensation and DNA fragmentation. Also the exposure to 1 microM
      deguelin resulted in the increase in early-apoptotic cells (Annexin V
      positive/Propidium iodide-negative) after 24 h, compared to the cells in the
      control medium (31 versus 12%). Deguelin-induced apoptosis involved the caspase-9
      and caspase-3 pathways in gastric cancer cells. Akt phosphorylation, hypoxia
      inducible factor-1alpha accumulation, and vascular endothelial growth factor
      expression in gastric cancer cells was inhibited by deguelin. Taken together,
      deguelin showed anticancer activity in gastric cancer cells, which is correlated
      with the inhibition of angiogenesis and induction of apoptosis. Deguelin may be a
      potential agent in inhibiting the progression of gastric cancer by virtue of its
      activity on these crucial cell characteristics.

PMID- 20811677
TI  - Role for ezrin in breast cancer cell chemotaxis to CCL5.
AB  - This study was undertaken to observe the effects and the possible mechanism of
      membrane-cytoskeleton linker ezrin on the chemokine CC chemokine ligand 5 (CCL5)
      induced invasive ability in human breast carcinoma MCF-7 cells. RNA interference
      (RNAi) using ezrin small hairpin RNAs (ezrin shRNA) was used to analyze the role
      of ezrin in the regulation of this CCL5-induced malignant behavior of MCF-7
      cells. The effects of recombinant human CCL5 (rhCCL5) on the cell's invasive
      ability were detected by transwell assay. Western blotting was performed to
      examine the expression of the total and the phosphorylated ezrin at protein
      level. The CCL5-induced changes in the organization of the actin cytoskeleton in
      the transfected cells were determined using confocal microscopy. Flow cytometry
      was used to detect the cell cycle. MTT method was used to detect the
      proliferation of the cells. We found that the MCF-7 cells responded
      chemotactically to CCL5 in a dose- and time-dependent manner. After RNAi
      treatment, the proliferation was inhibited and the cell proportion in G2-M phase
      decreased. The CCL5-induced cell motility and invasiveness were obviously
      inhibited by the silencing of ezrin. In addition, the CCL5 induced a significant
      up-regulation in the total and the phosphorylated ezrin expression in MCF-7
      cells, whereas in the presence of ezrin silencing, the CCL5 induced only a slight
      increase in the total and the phosphorylated ezrin expression. CCL5 was shown to
      induce changes in the organization of the actin cytoskeleton and the level of F
      actin in MCF-7 cells, and the silencing of ezrin could inhibit these changes.
      Collectively, our data further show that CCL5 induced invasiveness in MCF-7
      cells. These data indicate a potential role for ezrin in the processes of the
      CCL5-induced breast cancer cell migration, invasiveness and metastasis. It is
      suggested that ezrin may act as downstream effector of CCL5 and a new anti
      invasive therapeutic target for human breast cancer.

PMID- 20811678
TI  - Thermoseed hyperthermia treatment of mammary orthotopic transplantation tumors in
      rats and impact on immune function.
AB  - To evaluate the effect of thermoseed inductive heating on mammary orthotopic
      transplantation tumors and immunologic function in rats. Walker-256 tumor cells
      were inoculated subcutaneously into the mammary glands of Wistar rats. Rats were
      allocated to five treatment groups as follows: i) C group (control group); ii) M
      group (magnetic field group); iii) T group (thermoseed control group); iv) H1
      group (hyperthermia treatment, 45 degrees C for 30 min); v) H2 group
      (hyperthermia treatment, 50-55 degrees C for 10 min). Immediately, 12 and 24 h
      after hyperthermia, two rats were sacrificed in each group for pathological and
      immunohistochemical examination of the expression of PCNA and HSP70. Tumor volume
      was measured and long-term survival was observed. The T lymphocyte subgroup IL-2
      and IFN-gamma levels were measured in C, H1 and H2 groups. Both types of
      hyperthermia induced necrosis and apoptosis in the tumor tissue, decreased tumor
      volume (P<0.05), and increased survival time (P<0.01). The expression of PCNA and
      HSP70 in hyperthermia group was significantly different compared to the C, M and
      T groups (P<0.05), Hyperthermia increased CD4+ T lymphocytes and the levels of IL
      2 and IFN-gamma (P<0.05). Both types of hyperthermia can suppress the growth of
      mammary tumors and improve immunological function of rats.

PMID- 20811679
TI  - SATB1 is an independent prognostic marker for gastric cancer in a Chinese
      population.
AB  - Special AT-rich sequence binding protein 1 (SATB1), a new type of gene regulator,
      has been reported to express in various human cancers and may associate with the
      malignant potential. However, there are few data available on SATB1 expression
      and its relationship to tumor progression in gastric cancer. The current study
      was designed to examine the SATB1 expression in gastric cancer and to correlate
      it with clinical outcome. SATB1 expression was studied by qRT-PCR, western
      blotting and immunohistochemistry, respectively. The correlations between SATB1
      expression and clinicopathological factors were statistically analyzed. SATB1
      mRNA expression was significantly up-regulated in gastric cancer specimens as
      compared with that in normal tissues (P<0.001). Overexpression of SATB1 protein
      was observed in gastric cancer cell lines by western blotting. Fifty-three
      (44.9%) cases showed positive staining for the SATB1 proteins by
      immunohistochemistry. The expression of SATB1 mRNA agreed well with the western
      blotting and immunohistochemical findings (P<0.001). SATB1 expression was
      positively correlated with age, depth of invasion, lymph node metastasis, distant
      metastasis and TNM stage. Moreover, Kaplan-Meier analysis revealed that SATB1
      overexpression was associated with a significantly worse survival (P<0.001).
      Further multivariable analysis indicated that SATB1 expression was an independent
      prognostic indicator for gastric cancer (P=0.023). In summary, overexpression of
      SATB1 correlated with metastatic potential of human gastric cancer and would be a
      novel independent prognostic marker for predicting the outcome of gastric cancer.

PMID- 20811680
TI  - The chemokine receptor 7 regulates cell adhesion and migration via beta1 integrin
      in metastatic squamous cell carcinoma of the head and neck.
AB  - Migration and adhesion of tumor cells are essential prerequisites for the
      formation of metastases in malignant diseases. Chemokine receptor 7 (CCR7) has
      been shown to regulate integrin which can then facilitate adhesion of cancer
      cells to and/or migration through the extracellular matrix (ECM). In order to
      identify the connection between CCR7 and beta1 integrin, and the influence on
      cell adhesion and migration in metastatic squamous cell carcinoma of the head and
      neck (SCCHN). We use adhesion assays, migration assay, immunofluorescence
      staining, western blotting, and immunohistochemical analysis to find whether
      beta1 integrin can be activated by CCL19 (CCR7's ligand) and its role in SCCHN.
      The experiments were performed in the metastatic SCCHN cell line PCI-37B after
      pre-incubation of the cells with CCL19 and beta1 integrin inhibitors RGD-peptide.
      Our results demonstrate that CCR7 favours PCI-37B cell adhesion and migration,
      and induces reorganization of the actin cytoskeleton and up-expression of beta1
      integrin protein. beta1 integrin inhibitor RGD-peptide can block all these
      effects. Taken together, our data indicate that CCR7 regulate cell adhesion and
      migration via beta1 integrin in metastatic SCCHN, and these results can provide a
      basis for new strategies in preventing metastases of SCCHN.

PMID- 20811681
TI  - A pivotal role for Pim-1 kinase in esophageal squamous cell carcinoma involving
      cell apoptosis induced by reducing Akt phosphorylation.
AB  - It is well documented that Provirus integration site for Moloney murine leukemia
      virus 1 (Pim-1), as a proto-oncogene encoding a serine/threonine kinase with
      multiple cellular functions, is tightly associated with the occurrence and
      development of tumors. Overexpression of Pim-1 plays a critical role in the
      progression of several different tumors. In this study, esophageal squamous cell
      carcinoma (ESCC) EC9706 cells with Pim-1 siRNA treatment resulted in a clear
      decrease of Pim-1 levels, followed by inhibiting cell proliferation and inducing
      apoptosis. Further, Pim-1 siRNA reduced phosphorylation of Akt and Bad, and
      increased cleaved caspase-3/-9 activities and expression levels. These data
      suggest that Pim-1 siRNA-mediated apoptosis is closely related to the decrease in
      Akt and Bad phosphorylation and increase in cleaved caspase-3/-9 activities, and
      thus manipulation of Pim-1 is a potential target for molecular therapy in the
      clinical treatment of patients with ESCC.

PMID- 20811682
TI  - RhoA protein is generally distributed in the nuclei of cancer cells.
AB  - The aim of this study was to elucidate the localization of RhoA in human cancer
      tissues and cancer cell lines. Immunohistochemistry and immunofluorescence
      microscopy were used to determine the localization of RhoA in cancer tissues and
      cell lines, respectively. Western blotting was used to determine the quantity of
      RhoA in cell nucleus, cytosol and membrane. Immunofluorescence microscopy
      revealed that in all cell lines examined in this experiment (including SGC-7901,
      Hela, A549 and SW480), RhoA was localized not only on the membrane, in the
      cytosol, but also in the nucleus. Within the nucleus its precise localization was
      in the nucleolus. In the transformed gastric epithelial cell line GES, RhoA was
      also found to be localized on the membrane, in the cytosol and the nucleus, but
      the nuclear location was less than that of cancer cell lines.
      Immunohistochemistry microscopy revealed that in cancer tissues the nuclear RhoA
      was obviously more than that of para-cancer tissue; in the cancer tissues
      undergoing inflammation and necrosis, nuclear RhoA was even higher. RhoA is
      generally distributed in the nucleus of cells and the distribution increases when
      the cells undergo tumorigenesis, suggesting a new role for RhoA.

PMID- 20811683
TI  - Acquired resistance to miriplatin in rat hepatoma AH109A/MP10 is associated with
      increased Bcl-2 expression, leading to defects in inducing apoptosis.
AB  - Miriplatin, a novel lipophilic platinum complex approved to treat hepatocellular
      carcinoma, is administered into the hepatic artery after suspension in an oily
      contrast medium. Little is known concerning the mechanism of acquired resistance
      to miriplatin. In this study, we established and characterized a rat hepatoma
      cell subline, AH109A/MP10, which was about 10-fold more resistant to miriplatin
      than the parental cell line, AH109A. The established miriplatin-resistant cells
      showed clear cross-resistance to platinum complexes containing diaminocyclohexane
      as a carrier ligand, such as oxaliplatin and dichloro[(1R,2R)-1,2
      cyclohexanediamine-N,N']platinum (DPC), while three human cancer cell lines
      selected for resistance to cisplatin (A2780cis, NCI-H69/CPR, MOR/CPR) did not
      show cross-resistance to miriplatin. There was no apparent difference in either
      intracellular platinum accumulation or platinum-DNA adducts in formation between
      resistant and parental cells after treatment with miriplatin or cisplatin,
      consisted with the unchanged expression of proteins involved in DNA repair, such
      as excision repair cross-complementing 1 (ERCC1) and mutL homolog 1 (MLH1). The
      increased expression of Bcl-2 was observed in AH109A/MP10 cells, in which
      apoptosis induced by miriplatin, but not cisplatin, was reduced. In addition, Bcl
      2 inhibitor YC137 partially reversed the resistance of AH109A/MP10 cells to
      miriplatin. These findings suggested that the acquired resistance to miriplatin
      in AH109A/MP10 cells was associated in part with increased Bcl-2 expression,
      leading to defects in inducing apoptosis.

PMID- 20811684
TI  - VEGFR and EGFR inhibition increases epithelial cellular characteristics and
      chemotherapy sensitivity in mesenchymal bladder cancer cells.
AB  - The present study investigated the effect of VEGFR and EGFR inhibition via
      vandetanib (Zactima) on epithelial-mesenchymal transition (EMT) in bladder
      cancer. Markers of EMT (EGFR, VEGR, E-cadherin and vimentin) were interogated by
      Western blotting at baseline and after treatment with EGF, VEGF, vandetanib,
      cisplatin, or their combination using representative epithelial- and mesenchymal
      type human bladder cancer cells. Morphological changes induced by these
      treatments were examined by microscopy over various time courses. The effect of
      these changes on cisplatin chemotherapy sensitivity was assessed by MTT assay.
      RT4 and HTB3 cells had epithelial features while CRL1749 and J82 cells had
      mesenchymal features. After treatment with EGF, the epithelial-type cells
      demonstrated increased intercellular separation and pseudopodia, with these
      changes blocked by vandetanib. In contrast, the mesenchymal cells did not exhibit
      any morphological changes with the EGF treatment but adopted a
      clustered/epithelial appearance after the administration of vandetanib. Western
      blotting shows that treatment of epithelial cells with vandetanib increased the
      expression of E-cadherin. In comparison, mesenchymal cells demonstrated decreased
      vimentin expression with the treatment of vandetanib in the presence of EGF and
      VEGF. Improved growth inhibition was seen in the epithelial cells but not in
      mesenchymal cells with the concurrent treatment of vandetanib and cisplatin.
      Sequential treatment of mesenchymal cells with vandetanib followed by cisplatin
      demonstrated synergy with improved cisplatin activity. The findings offer a novel
      role of vandetanib on the EMT in bladder cancer, providing insight into EMT in
      bladder cancer.

PMID- 20811685
TI  - Possibility of paclitaxel as an alternative radiosensitizer to 5-fluorouracil for
      colon cancer.
AB  - To evaluate the feasibility of paclitaxel (PTX) radiosensitization for colon
      cancer, we investigated the cytotoxic and G2/M checkpoint protein (Chk1, Wee1,
      Bub1, MAD2) effects of 5-fluorouracil (5-FU) or PTX combined with radiation in
      the human colon cancer cell line LoVo. Cytotoxicity and radiocytotoxicity were
      evaluated for each drug by the WST-8 colorimetric assay. The IC20 for each drug
      was determined as a cytotoxic concentration from a survival curve. LoVo cells
      were exposed to the IC20 of each drug for 24 h and then irradiated. Expressions
      of the G2/M checkpoint proteins were confirmed by Western blot analysis.
      Cytotoxicity was induced by 5-FU or PTX alone in a time- and dose-dependent
      manner. The IC20 of PTX caused higher radiosensitivity than the IC20 of 5-FU
      (P<0.05). Western blot analysis revealed different expression patterns of the
      G2/M checkpoint proteins between 5-FU and PTX pre-treatments. 5-FU combined with
      radiation tended to decrease the expressions of all G2/M checkpoint proteins in a
      time-dependent manner. PTX combined with radiation maintained high expressions of
      Chk1 and MAD2 proteins for 24 h post-radiation and, in particular, MAD2 protein
      was strongly induced by PTX with high-dose radiation. PTX showed higher radio
      sensitization than 5-FU for the colon cancer cell line LoVo and may be an
      alternative radiosensitizer to 5-FU in the clinical setting.

PMID- 20811686
TI  - WNT pathway in oral cancer: epigenetic inactivation of WNT-inhibitors.
AB  - Epigenetic DNA methylations plays an important role in oral carcinogenesis. The
      soluble frizzled receptor protein (SFRP) family together with WIF-1 and DKK-3
      encodes antagonists of the WNT pathway. Silencing of these genes leads to
      constitutive WNT signalling. Because aberrant expression of beta-catenin might be
      associated with the epigenetic inactivation of WNT inhibitors, we analyzed, in a
      collection of primary OSCC with matched normal oral mucosa, the methylation
      status of a complete panel of genes, SFRP-1, SFRP-2, SFRP-4, SFRP-5, WIF-1, DKK
      3, that are involved directly and indirectly in WNT pathway, in order to
      demonstrate WNT-pathway activation in the absence of beta-catenin and/or APC/Axin
      mutations during oral carcinogenesis. Methylation-specific PCR (MSP) was
      performed to study inactivation of SFRP-1, SFRP-2, SFRP-4, SFRP-5, WIF-1, DKK-3
      genes in 37 cases of paraffin embedded oral cancer. This study showed that the
      methylation is an important epigenetic alteration in oral cancer. In particular,
      SFRP-2, SFRP-4, SFRP-5, WIF-1, DKK-3 revealed methylation status of their
      promoter in OSCC, whereas SFRP-1 showed demethylation in cancer. Fisher's exact
      test revealed statistically significant results (p<0.05) for all genes. The Wald
      test confirmed the statistically significant association between SFRP2-4-5 gene
      methylation and OSCC (p<0.05). SFRP-1 was also characterized by a different
      statistically significant epigenetic behaviour, because of it was demethylated in
      cancer (p<0.05). Statistical regression test showed high levels of sensitivity,
      specificity and accuracy for SFRP genes, while WIF-1 and DKK-3 have reportedly
      high specificity, moderate accuracy but low sensitivity. This study suggests that
      a cause of catenin delocalization in oral cancer could be due to WNT pathway
      activation, by epigenetic alterations of SFRP, WIF-1 and DKK-3 genes.

PMID- 20811687
TI  - Up-regulation of NKG2F receptor, a functionally unknown killer receptor, of human
      natural killer cells by interleukin-2 and interleukin-15.
AB  - The NKG2 family receptors are C-type lectin, type II transmembrane molecules, and
      play important roles in regulation of natural killer (NK) cell functions against
      tumor and virus. NKG2F is a new member of NKG2 family, and may possibly associate
      with DAP 12 to activate NK cells. Since lacking available antibody against human
      NKG2F, the features of NKG2F expression on NK cells remains unclear. In this
      study, human NKG2F recombinant expression in E. coli was carried out by using pET
      28a with a hexahistidine (6x His) tag and a thrombin digestion sequence to the N
      terminus of the recombinant protein NKG2F. IPTG (isopropyl-beta-d-thio
      galactoside) induction resulted in high expression of recombinant NKG2F protein,
      which was then purified and identified by anti-His western blotting and LC-MS/MS.
      Polyclonal antibody was produced by immunization of BALB/c mice with recombinant
      NKG2F, and then used to detect NKG2F in western blotting and flow cytometry. Our
      results demonstrated that NKG2F was expressed only by PBMCs but not by human NK
      cell lines such as NKL and YT at mRNA level. It was observed that NKG2F was
      expressed on surface of human blood NK cells, and may be up-regulated at mRNA
      level and protein level after IL-2 or IL-15 stimulation.

PMID- 20811688
TI  - Sorafenib enhances the in vitro anti-endothelial effects of low dose (metronomic)
      chemotherapy.
AB  - Angiogenesis inhibitors may enhance the effects of low dose (metronomic)
      chemotherapy. However, there is a wide range of novel angiogenesis inhibitors
      which must be tested in combinations with oral chemotherapy agents to assess the
      anti-endothelial and anti-cancer effects. This preliminary testing is most suited
      to high throughput in vitro models, rather than clinical trials. We aimed to
      establish an in vitro model and test the anti-endothelial and anti-cancer effects
      of the multi-kinase inhibitor sorafenib when used as a single agent and in
      combination with oral chemotherapy agents used at low concentrations. Micro
      vascular endothelial cells and 3 cancer cell lines were utilised and an extended
      treatment strategy (96 h) was employed in order to mimic a continuous low dose
      anti-angiogenic chemotherapy regimen. Sorafenib significantly enhanced the anti
      endothelial effect of low dose etoposide, paclitaxel and temozolomide. Sorafenib
      also significantly enhanced the anti-cancer effect of low dose etoposide,
      paclitaxel and temozolomide in SK-MEL-2 melanoma cells, producing an additive
      effect on inhibition of cell growth in all cases. These combinations appear to be
      the most promising for in vivo pre-clinical studies, with a view to testing in
      melanoma patients as a continuous dosing strategy, due to the in vitro additive
      inhibitory effect on growth seen in both endothelial and cancer cells.

PMID- 20811689
TI  - Inhibition of tankyrase 1 in human gastric cancer cells enhances telomere
      shortening by telomerase inhibitors.
AB  - Telomere stability is believed to be related to aging and tumorigenesis. Besides
      telomerase, telomere length is also regulated by several telomere-specific
      binding proteins. Tankyrase 1, a telomeric poly(ADP-ribose) polymerase (PARP),
      elongates telomere length by inhibiting TRF1 binding to telomeres. In order to
      study the synergistic action of tankyrase 1 and telomerase in the maintenance of
      telomere length in mammalian cells, we constructed anti-sense tankyrase 1 (aTNKS)
      eukaryotic expression vectors and then transfected them into the SGC-7901 human
      gastric cancer cell line, as well as SGC-7901 cells that had been transfected
      with antisense hTR (7901-ahTR) and antisense hTERT (7901-ahTERT) with DOTAP
      liposomes. The activity of telomerase, telomere length and telomerase-associated
      protein activities were measure by TRAP-ELISA, Southern blot and western blot
      analysis, respectively, in aTNKS transfected and untransfected cells. The results
      demonstrated that telomere length was significantly shorter in cells with
      concomitant tankyrase 1 and telomerase inhibition than by either tankyrase 1 or
      telomerase inhibition alone, in SGC-7901 cells. We also found that aTNKS had no
      effect on telomerase activity. These results reveal that inhibition of tankyrase
      1 could shorten telomere length and play a synergistic role with telomerase
      inhibitors in telomere length shortening in the SGC-7901 gastric cancer cell
      line. Co-inhibition of tankyrase 1 and telomerase activity may be a rational
      strategy for telomere-directed gastric cancer therapeutics.

PMID- 20811690
TI  - Establishment of a rhabdomyosarcoma xenograft model in human-adapted mice.
AB  - The outcome of patients with advanced stage rhabdomyosarcoma (RMS) is still
      sobering. This outcome has not improved through conservative treatments.
      Therefore, novel treatment approaches such as immunotherapy need to be evaluated
      in human-adapted animal models. The aim of this study was to develop a humanized
      mouse model of childhood RMS as a basis for the study of immunotherapeutic
      approaches. Therefore, NOD/LtSz-scid IL2rgammanull-mice were used for all the
      experiments (n=19). The animals underwent sublethal irradiation on days 1 and 2
      (1 x 300 cGy). After irradiation, the transplantation of human CD34+-cells
      (1,000,000 cells per animal i.v.) was carried out. Five animals served as the
      control and did not undergo stem cell transplantation. The engraftment of human
      cells was assessed in peripheral blood on days 21 and 55 by FACS analysis. Eight
      weeks after transplantation, the subcutaneous xenotransplantation of human
      alveolar and embryonal RMS cell lines was carried out. Tumor growth was monitored
      and tumors were resected 93 days after CD34+-transplantation. The tumor specimens
      were evaluated histologically. The successful engraftment of human cells with the
      establishment of a human immune system was observed in 12 out of 14 animals. B
      and T cells were mostly detected in the peripheral blood. There were only a few
      monocytes and almost no natural killer cells. The xenotransplantation of alveolar
      RMS resulting in subcutaneous tumor growth was feasible in 7 animals. The
      xenotransplantation of embryonal RMS was performed in 5 animals and led to tumor
      growth in 1 animal. A histological work up showed either alveolar or embryonal
      RMS cells with central necrosis. This is the first time a xenotransplantation
      model of human RMS has been developed in a humanized mouse model. The
      establishment of subcutaneous tumor xenografts was more effective in the alveolar
      subtype. This model offers a basic tool for further analyzing novel
      immunotherapeutic approaches in RMS, and could possibly be used in other solid
      pediatric tumors.

PMID- 20811691
TI  - Association between metalloproteinases 2 and 9 activity and ERK1/2
      phosphorylation status in head and neck cancers: an ex vivo study.
AB  - Advances in clinical treatment of head and neck squamous cell carcinoma (HNSCC)
      are hampered by its high infiltrative potential leading to distal metastasis.
      Since their ability to degrade the basal lamina and extracellular matrix, matrix
      metalloproteinases (MMP) have a pivotal role in tumor invasion. The
      overexpression and the aberrant activity of MMPs especially of MMP2 and MMP9,
      during HNSCC development and progression have been reported. However, up to now
      little is known about the mechanism of their regulation in HNSCC. It has been
      demonstrated that MMP2/9 expression is negative regulated by extracellular signal
      regulated kinase 1 and 2 (ERK1/2) in HNSCC cell lines. ERKs are protein kinases
      belonging to the mitogen-activated protein kinases family, and they are involved
      in the regulation of different cellular aspects, from apoptosis to cell
      proliferation and differentiation. In the present study we evaluated MMP2 and
      MMP9 activity by gelatine zymography in 16 tissue samples of HNSCC and their
      paired normal mucosa from patients undergoing surgical treatment. Moreover,
      ERK1/2 activation was analyzed by immunoblotting. A statistically significant
      decrease in the levels of activated ERK2 in cancer specimens in comparison with
      paired normal tissues was observed, whereas a significant increase in the
      activity of MMP2 was found in cancer specimens. However, the statistical analysis
      failed to demonstrate a correlation between the increase in MMP2 activity and the
      reduction of ERK1/2 activation levels. The results obtained, therefore, rule out,
      for the first time in an ex vivo study, the existence of a negative correlation
      between ERK1/2 activation and MMP2 activity.

PMID- 20811692
TI  - The role of common variants of non-homologous end-joining repair genes XRCC4,
      LIG4 and Ku80 in thyroid cancer risk.
AB  - Variations, such as single nucleotide polymorphisms (SNPs) in DNA damage repair
      genes have been pointed out as possible factors to cancer predisposition.
      Ionizing radiation (IR) induces DNA double strand breaks (DSBs) and is the main
      recognized risk factor for thyroid cancer. However, most of the patients do not
      show chronic contact with IR and the other factors have non-concordant data.
      Thus, thyroid cancer could be due to gene variations in association with certain
      exogenous factors. One of the pathways that repair DSBs is DNA non-homologous end
      joining (NHEJ) that comprises several polymorphic genes. We intend to study the
      role of polymorphic variants in XRCC4, LIG4 and Ku80 genes, since there is
      scarcity of data on the role of these genes in thyroid cancer susceptibility. We
      carried out a hospital-based case-control study in a Caucasian Portuguese
      population (109 patients and 217 controls) to estimate the potential role of the
      XRCC4 (N298S and T134I), LIG4 (T9I) and Ku80 (Ex21-238Gright curved arrow A,
      Ex21+338Tright curved arrow C, Ex21-352Cright curved arrow A, Ex21+466Aright
      curved arrow G) polymorphisms in the individual susceptibility for this disease.
      The results here reported do not associate these polymorphisms with
      susceptibility for non-familial thyroid cancer. However, when the data were
      analyzed according to the type of tumour, significant results for Ku80 Ex21
      238Gright curved arrow A and Ex21+466Aright curved arrow G were found for
      papillary tumours (adjusted OR = 2.281; 95% CI =; 1.063-4.894; P=0.034). Taken
      together these results suggest that some of these variants in NHEJ genes can
      contribute to thyroid cancer susceptibility. However, further studies with a
      larger sample size will be needed to support our results.

PMID- 20811693
TI  - Pomegranate extract inhibits the proliferation and viability of MMTV-Wnt-1 mouse
      mammary cancer stem cells in vitro.
AB  - Pomegranate (Punica granatum L.) is known to possess anticancer activities. The
      effects of a standardized extract of pomegranate (PE) on a mouse mammary cancer
      cell line (designated WA4) derived from mouse MMTV-Wnt-1 mammary tumors were
      examined in this study. The WA4 cell line has been previously characterized as
      containing a majority of cells possessing stem cell characteristics. PE inhibited
      the proliferation of WA4 cells in a time- and concentration-dependent manner.
      This was due to an arrest of cell cycle progression in the G0/G1 phase. PE was
      also cytotoxic to quiescent WA4 cells in a concentration-dependent manner at
      concentrations >10 microg/ml. PE treatment of WA4 cells resulted in an increase
      in caspase-3 enzyme activity in a time- and concentration-dependent manner,
      indicating that the cytotoxic effect of PE was due to the induction of apoptosis.
      We tested the effect of several individual phytochemicals derived from PE on WA4
      cells. Ellagic acid, ursolic acid and luteolin caused a time- and concentration
      dependent reduction of cell proliferation and viability, suggesting that they
      contribute to the inhibitory effect of PE, while caffeic acid had no effect.
      Cancer stem cells, which are highly resistant to conventional chemotherapeutic
      agents, are thought to be the origin of both primary and secondary breast tumors,
      and thus are a critical target in both breast cancer therapy and prevention.
      These data suggest that PE, which is a proven and safe dietary supplement, has
      promise as an treatment against breast cancer by preventing proliferation of
      cancer stem cells.

PMID- 20811694
TI  - beta-catenin siRNA regulation of apoptosis- and angiogenesis-related gene
      expression in hepatocellular carcinoma cells: potential uses for gene therapy.
AB  - The molecular mechanism responsible for hepatocellular carcinoma (HCC)
      development remains to be defined although a number of gene pathways have been
      shown to play an active role, such as Wnt/beta-catenin signaling. In this study,
      beta-catenin small interfering RNA (siRNA) was designed, synthesized, and
      transfected into HCC HepG2 cells. RT-PCR and western blot assays were performed
      to detect expression of altered genes and proteins, and the MTT assay was used to
      detect cell viability. Our data showed that beta-catenin mRNA and protein
      expression levels were effectively knocked down by beta-catenin siRNA and
      subsequently, tumor cell proliferation was significantly suppressed. Flow
      cytometry assay showed that tumor cells were arrested at the G0/G1 phase of the
      cell cycles. Molecularly, expression of Smad3, p-caspase-3, and Grp78 protein
      were upregulated after 72 h of beta-catenin siRNA transfection, whereas
      expression of TERT, caspase-3, XIAP, MMP-2, MMP-9, VEGF-A, VEGF-c, and bFGF
      protein were reduced. However, there was no change between the expression of
      STAT3 and the HSP27 protein following transfection. The results from the current
      study demonstrated the importance of the Wnt/beta-catenin signaling pathway in
      regulation of gene expression in HCC. Further studies are required to investigate
      the role of this pathway in HCC development and targeting of this pathway to
      control HCC.

PMID- 20811695
TI  - Predictive significance of the cut-off value of CD20 expression in patients with
      B-cell lymphoma.
AB  - The introduction of the anti-CD20 monoclonal antibody, rituximab, into the
      treatment of patients with B-cell lymphomas has improved the overall response
      rate, as well as the response duration and the overall survival of these
      patients. However, only a few studies have addressed the question of whether
      higher CD20 expression parallels with better treatment outcomes. The aim of this
      study was to assess the relationship between the level of CD20 expression and
      overall survival (OS), disease-free survival (DFS) along with the overall
      response rate (ORR) in B-cell lymphoma patients. The ultimate objective of the
      study was to determine the cut-off value of CD20 expression together with the
      predictive significance of better outcome of rituximab treatment. One hundred and
      fourteen patients with different histological types of B-cell lymphomas treated
      with rituximab and chemotherapy between 2003 and 2007 were enrolled in the study.
      All patients had CD20 expression assessed prior to the beginning of treatment.
      The level of CD20 expression was determined by quantitative flow cytometric
      measurements, while the OS and DFS were evaluated by means of Kaplan-Meier
      survival curves. The cut-off value of CD20 expression, which predicts a better
      response to rituximab in patients with B-cell lymphomas, was determined at 25.000
      molecules of equivalent soluble fluorochrome (MESF). Our data show that patients
      who achieved complete response after rituximab therapy had a significantly higher
      expression of the CD20 antigen (p=0.018) than those whose disease only stabilized
      after rituximab therapy. No significant difference was observed in the response
      duration between the patients with CD20 antigen expressed above the cut-off value
      and those expressing CD20 antigen below the cut-off value [hazard ratio (HR),
      0.5667; 95%CI, 0.124 to 3.18, p=0.57]. Even though we have proved that patients
      with a CD20 expression level above the cut-off value treated with rituximab had a
      significantly longer OS [hazard ratio (HR), 0.4573; 95%CI, 0.1364 to 0.9461,
      p=0.0383] than patients with a CD20 expression level below the cut-off value.
      Among our study population, 17.5% had a CD20 expression level below the cut-off
      value. The highest percentage (80%) of the patients with a CD20 expression level
      below the cut-off value belonged to the group of chronic lymphocytic leukemia
      (CLL) patients, while the lowest (6.7%) was observed in the follicular lymphoma
      (FL) patient group. These data indicate that a higher level of CD20 expression
      correlates with an improved OS in patients treated with rituximab. The cut-off
      limit of CD20 expression suggested to have the predictive significance of better
      outcome was in our series set at 25.000 MESF. This cut-off value should be
      considered when the decision regarding treatment with rituximab is taken.
      However, these results warrant further studies on larger groups of patients.

PMID- 20811696
TI  - Inter-related in vitro effects of androgens, fatty acids and oxidative stress in
      prostate cancer: a mechanistic model supporting prevention strategies.
AB  - Oxidation of mitochondrial fatty acids (FA) results in the generation of reactive
      oxygen species (ROS) which have been postulated to play a key role in the
      initiation and progression of prostate cancer (PC). We previously reported that
      androgens increase FA uptake into PC cells. We thus examined if androgens that
      are known to induce ROS generation regulate FA oxidation in PC cells. The effects
      of the androgen-depleted medium, R1881 (synthetic androgen) and/or androgen
      receptor blocker, bicalutamide were examined in the human androgen-responsive but
      not dependent 22rv1 cells. R1881 supplementation significantly increased
      mitochondrial FA oxidation ((14)C-radiolabeled FA degradation studies), resulting
      in increased ROS production. Androgens increased the mRNA levels of carnitine
      palmitoyltransferase (CPT1), the rate limiting enzyme in the process of
      mitochondrial FA oxidation. Treatment with R1881 and bicalutamide inhibited these
      androgen regulated effects. Inhibition of mitochondrial ROS generation by two
      different inhibitors, rotenone and thenoyltrifluoroacetone, eliminated the
      androgen-induced ROS generation, to the same level as in cells deprived of
      androgens or treated with R1881 and bicalutamide. Taken together, androgens
      increase the mitochondrial oxidation of FA, leading to increased production of
      ROS that is associated with prostate cell proliferation and mutagenesis. These
      results therefore support the rationale for PC prevention using 5-alpha reductase
      inhibitors, dietary restrictions or anti-oxidants, each of which has different
      inhibitory but complementary effects.

PMID- 20811697
TI  - Effects of vandetanib on adenoma formation in a dextran sodium sulphate enhanced
      Apc(MIN/+) mouse model.
AB  - The Apc(MIN/+) mouse is a well-characterised model of intestinal tumourigenesis
      in which animals develop macroscopically detectable adenomas. However, most of
      the adenomas are formed in the small intestine and resolution of events in the
      colon, the most relevant site for human disease, is limited. Inducing colitis
      with dextran sodium sulphate (DSS) can selectively enhance the development of
      lesions in the colon. We demonstrated that a DSS pre-treatment is well tolerated
      and effective at inducing colon adenomas in an Apc(MIN/+) mouse model. We then
      investigated the effect of inhibiting vascular endothelial growth factor (VEGFR)-
      and epidermal growth factor receptor (EGFR)-dependent signalling pathways on the
      development of adenomas induced in DSS-pretreated (DSS/Apc(MIN/+)) or non-DSS
      pretreated (Apc(MIN/+)) mice using vandetanib (ZD6474), a potent and selective
      inhibitor of VEGFR and EGFR tyrosine kinase activity. Eight-week old Apc(MIN/+)
      mice were given either drinking water or 1.8% DSS and then vandetanib (ZD6474)
      (50 mg/kg/day) or vehicle by oral gavage for 28 days and sacrificed 24 h after
      the last dose and assessed for adenoma formation in the intestines. DSS pre
      treatment was well tolerated and significantly enhanced formation of adenomas in
      the colon of control Apc(MIN/+) mice. Vandetanib treatment significantly reduced
      adenoma formation in the small intestine by 68% (P=0.001) and the colon by 77%
      (from 13.8 to 3.1, P=0.01) of DSS-pretreated Apc(MIN/+) mice. In the Apc(MIN/+)
      group, vandetanib also reduced the mean number of adenomas in the small intestine
      by 76% (P<0.001) and in the colon by 60% (from 3.9 to 1.5, P=0.1). DSS-pre
      treatment increased the resolution of the model, allowing us to confirm
      statistically significant effects of vandetanib on the development and growth of
      colon adenomas in the Apc(MIN/+) mouse. Moreover these preclinical data provide a
      rationale for studying the effects of vandetanib in early stages of intestinal
      cancer in the clinic.

PMID- 20811698
TI  - Novel bladder preservation therapy for locally invasive bladder cancer: combined
      therapy using balloon-occluded arterial infusion of anticancer agent and
      hemodialysis with concurrent radiation.
AB  - We investigated the effect of balloon-occluded arterial infusion (BOAI) of
      anticancer agent (cisplatin/gemcitabine), used concomitantly with hemodialysis,
      which delivers an extremely high concentration of anticancer agent to the site of
      a tumor without systemic adverse effects, along with concurrent radiation
      (referred to as the OMC-regimen) in patients with advanced bladder cancer. One
      hundred and ninety-two patients were assigned to receive either the OMC-regimen
      (n=96) or total cystectomy (n=96). Patients in the OMC-regimen group who failed
      to achieve CR underwent cystectomy, or secondary BOAI with an increased amount of
      CDDP or gemcitabine (1600 mg). The OMC-regimen allowed >89% (69/77) of patients
      with locally invasive tumors to achieve CR [>70% (70/96) of all patients
      including those with T4 and N(+) disease]. Most (68/69) of the CR patients were
      still alive with no evidence of recurrence after a mean follow-up of 161 (range
      12-805) weeks. The 5- and 15-year overall survival rates were 91.5 and 81.3% (vs.
      59.8% and 40.1% for cystectomy, P<0.0001), respectively. No patients suffered
      Grade III or more severe toxicities. In contrast, at 5 and 15 years after surgery
      in the total cystectomy group, about 50 and 60% of patients had suffered disease
      progression or had died, respectively. The OMC-regimen, a new bladder
      preservation strategy for patients with locally invasive bladder cancer, can be
      curative not only in patients for whom cystectomy is indicated, but also in
      patients whose condition is not amenable to curative treatment and for whom
      merely palliative therapy would otherwise seem the only option.

PMID- 20811699
TI  - Histone deacetylase inhibitors valproic acid and depsipeptide sensitize
      retinoblastoma cells to radiotherapy by increasing H2AX phosphorylation and p53
      acetylation-phosphorylation.
AB  - Although p53 is intact in most cases of retinoblastoma, it is largely inactivated
      by the ubiqutin-proteasome system through interaction with murine double minute 2
      (MDM2) and murine double minute X (MDMX). The present study showed that the
      histone deacetylase (HDAC) inhibitors valproic acid (VPA) and depsipeptide
      (FK228) synergistically enhanced ionizing radiation (IR)-induced apoptosis,
      associated with activation of caspase-3 and cleavage of poly(ADP-ribose)
      polymerase in Y79 and WER1-Rb1 human retinoblastoma cells. Both VPA and FK228
      enhanced IR-induced phosphorylation of histone H2AX on Ser139 preceding
      apoptosis. Exposure of cells to IR in the presence of VPA or FK228 induced the
      accumulation of p53 acetylated at Lys382 and phosphorylated at Ser46 through the
      reduction of binding affinity with MDM2 and MDMX. These results suggest that
      acetylation of p53 by HDAC inhibitors is a promising new therapeutic target in
      refractory retinoblastoma.

PMID- 20811700
TI  - Midkine expression is correlated with an adverse prognosis and is down-regulated
      by p53 in oral squamous cell carcinoma.
AB  - Midkine (MK) expression has been documented to be inversely correlated with the
      prognosis of patients with various tumors, but the mechanism of this relationship
      has not been well characterized. Recent studies have also correlated p53
      expression with prognosis of patients with oral squamous cell carcinoma (OSCC).
      We evaluated the relationship between MK expression and clinicopathological
      features of patients with OSCC to clarify the influence of p53 status on MK
      expression in OSCC cells. Our results showed that patients with MK over
      expression in OSCC cells had a significantly lower 5-year survival rate compared
      with patients with low MK expression. Immunohistochemical analyses demonstrated
      overexpression of MK protein in OSCC samples with mutant p53. Cell culture
      experiments with human lingual squamous cell carcinoma revealed that the MK gene
      was regulated by the wild-type p53 gene. Thus, MK expression may affect prognosis
      via the p53 status and mutation of the p53 gene, and MK may be an attractive
      target for therapeutic intervention in patients with cancer cells with mutant
      p53.

PMID- 20811701
TI  - Functional cell surface expression of toll-like receptor 9 promotes cell
      proliferation and survival in human hepatocellular carcinomas.
AB  - Toll-like receptor 9 (TLR9) is a pattern-recognition receptor that is involved in
      immune signaling and plays a crucial role in cell survival through recognition of
      various bacterial and viral components including unmethylated CpG-DNA. TLR9
      expression and function in cancer cells are not well understood. We investigated
      the expression of TLR9, and the function of TLR9 signaling, in hepatocellular
      carcinoma (HCC) cells following stimulation with CpG-oligodeoxynucleotides
      (ODNs). Positive immunohistochemical staining for TLR9 was observed in 85.7% of
      HCC tissues. Western blot analysis revealed that TLR9 was expressed both on the
      cell membrane and in the cytoplasm of HCC cell lines. Full-length TLR9 was
      predominantly expressed on the membrane rather than in the cytoplasm, whereas
      multiple cleaved forms of TLR9 were predominantly expressed in the cytoplasm
      rather than on the membrane. Cell surface stimulation of TLR9 promoted cell
      proliferation, and, furthermore, the TLR9 agonists, CpG-ODNs, reduced the
      cytotoxicity of the anti-cancer drug adriamycin (ADM) via up-regulation of
      apoptosis inhibitors such as survivin, Bcl-xL, XIAP and cFLIP, in HCC cell lines.
      Although cell surface stimulation of TLR9 did not activate either the NF-kappaB
      signaling pathway or the type-I IFN secretion pathway, gene chip microarray
      analysis indicated that TLR9 agonists closely regulated multiple oncology-related
      genes and transcription factors involved in tumorigenesis and cancer progression.
      In conclusion, our results indicate that functional cell surface expression of
      TLR9 in human HCC may play an important role in tumorigenesis and cancer
      progression.

PMID- 20811702
TI  - Clarithromycin attenuates autophagy in myeloma cells.
AB  - It has been reported that clarithromycin (CAM) augments the anti-tumor activity
      of thalidomide against multiple myeloma (MM) cells, while the mechanism remains
      unclear. A myeloma cell line or primary myeloma cells were treated with CAM.
      Autophagy was analyzed by morphological changes, LC3 expression and lysotracker
      staining. CAM induced vacuoles in the cytoplasm of MM cells which resembled
      autolysosomes. The manifestation of the CAM-induced vacuoles was blocked by
      treatment with PI3-kinase inhibitor. CAM induced an accumulation of LC3-II
      without affecting the mTOR or AKT pathways, eventually leading to cell death. CAM
      may halt the autophagy process after fusion of autophagosomes with lysosomes.
      This phenomenon may explain how CAM, combined with thalidomide, augments the
      cytotoxic effects of the latter on MM cells and suggests that modification of
      autophagy might represent a new approach for therapy of MM.

PMID- 20811703
TI  - The role of autophagy in the treatment of pancreatic cancer with gemcitabine and
      ionizing radiation.
AB  - Autophagy has recently emerged as a significant mechanism in cancer treatment.
      Although gemcitabine and/or ionizing radiation are important modalities in the
      treatment of pancreatic cancer, the contribution of autophagy in such treatment
      has not been fully elucidated. This study investigated the role of autophagy in
      the treatment of pancreatic cancer with gemcitabine and ionizing radiation. To
      evaluate the effect of gemcitabine and/or ionizing radiation on autophagy,
      several human pancreatic cancer cell lines were used. The treatment of pancreatic
      cancer cell cultures in vitro and in vivo with gemcitabine and ionizing radiation
      resulted in synergistic cytotoxicity. After treatment with gemcitabine, the
      autophagy-related protein light chain 3-II (LC3-II) was upregulated. When
      gemcitabine was combined with ionizing radiation treatment, LC3-II upregulation
      was enhanced. In addition, electron microscopy of pancreatic cancer cells treated
      with gemcitabine and/or ionizing radiation detected the induction of autophagy.
      The blockage of autophagy by 3-methyladenine indicated that autophagy contributed
      to cell death after gemcitabine treatment and enhanced its cytotoxicity. The
      inhibitory effect and immune reactivity of the autophagy-related proteins LC3 and
      beclin-1 were the strongest after the combination treatment. In conclusion, these
      results suggest that autophagy can be activated by gemcitabine and/or ionizing
      radiation in the treatment of pancreatic cancer cells and that activated
      autophagy plays a role in cancer suppression. These findings may have important
      implications for future therapeutic strategies using gemcitabine and ionizing
      radiation against pancreatic cancer.

PMID- 20811704
TI  - The use of protein array to identify targetable receptor tyrosine kinases for
      treatment of human colon cancer.
AB  - Several studies have reported that activated receptor tyrosine kinases (RTKs) are
      highly expressed in colon cancer and may promote tumor growth and survival.
      However, there is little information available as to the function and signaling
      of RTKs in colon cancers. In the present study, we performed protein array
      technology to determine the expression status of various RTKs that are activated
      in colon cancer compared to normal colonic cells and tissues. Of the 42 different
      phospho-RTKs, 5 (ErbB2, FGFR1, FGFR2a, FGFR3 and MSPR) were activated in Caco-2,
      SW480, WiDr, Lovo colon cancer cell lines and cancerous tissues. In order to
      determine the effect of inhibition of RTKs, especially ErbB2, athymic nude mice
      bearing xenograft tumors were treated with the ErbB2-targeting drug trastuzumab
      alone, or in combination with 5-Fluorouracil (5-FU). Similar to the treatment of
      5-FU alone, trastuzumab suppressed the growth of colon cancer. Combination
      therapy of trastuzumab and 5-FU inhibited tumor growth significantly compared to
      the treatment of 5-FU alone or trastuzumab alone. In addition, xenograft tumors
      were also analyzed by phospho-MAPK protein array. The activity of Akt3/PKBgamma
      was inhibited with 5-FU alone and trastuzumab, indicating that trastuzumab may
      inhibit colon cancer growth through ErbB2-Akt3/PKBgamma signaling. These data
      demonstrate that ErbB2 could be an important candidate for colon cancer therapy
      and the addition of trastuzumab to 5-FU therapy might augment the clinical
      response in colon cancer patients. Therefore, the analysis of phospho-RTK
      expression by protein array as a useful tool might identify novel therapies for
      individual patients with colon cancer.

PMID- 20811705
TI  - The role of serum response factor in hepatocellular carcinoma: implications for
      disease progression.
AB  - Serum response factor (SRF) regulates transcription of the immediate early genes
      and triggers proliferation, migration and differentiation in several types of
      cells. We examined the role of SRF in HCC by transfecting the SRF cDNA in HLE
      cells and the SRF anti-sense cDNA in sarcomatoid HCC cells. The overexpression of
      SRF in the HLE cells significantly increased the cell growth and proliferation.
      Overexpression of SRF increased actin polymerization of the HCC cells and induced
      morphologic changes. The mesenchymal markers vimentin, N-cadherin and RhoA were
      highly expressed in the SRF-transfected HLE cells. Furthermore, the
      overexpression of SRF in the HLE cells increased the expression levels of the
      active form of the beta-catenin and Wnt/beta-catenin target genes, such as c-myc
      and cyclin D1. The overexpression of SRF significantly enhanced the cell
      migration and invasiveness of HCC cells. Conversely, inhibition of the SRF
      expression in the sarcomatoid SH-J1 cells by the SRF anti-sense cDNA
      significantly decreased migration and invasion through the attenuated expression
      of mesenchymal markers and the proteins involved in the Wnt/beta-catenin pathway.
      These results indicate that the overexpression of SRF in HCC cells modulates the
      Wnt/beta-catenin pathway, and this plays an important role in HCC progression.

PMID- 20811706
TI  - Ribonucleotide reductase subunit M1 assessed by quantitative double-fluorescence
      immunohistochemistry predicts the efficacy of gemcitabine in biliary tract
      carcinoma.
AB  - Gemcitabine is a commonly used chemotherapeutic agent for advanced biliary tract
      carcinoma (BTC), although its efficacy is insufficient. Therefore, it is
      essential to establish new diagnostic methods, which can predict responders
      before the treatment. The aim of this study is to identify the most reliable
      chemoresistance marker to gemcitabine in BTC among the 4 molecules (hENT1, dCK,
      RRM1 and RRM2) involved in gemcitabine metabolism. The expression of 4 molecules
      were investigated in 5 BTC cell lines, and correlated with gemcitabine
      sensitivity. RRM1 protein was also assessed by quantitative double-fluorescence
      immunohistochemistry (qDFIHC) in 10 patients with unresectable or recurrent BTC
      who received gemcitabine-based chemotherapy. RRM1 and RRM2 protein strongly
      correlated with the IC(50) value for gemcitabine in BTC cell lines (R=0.935,
      0.771, respectively). In addition, patients with low RRM1 were significantly more
      sensitive to gemcitabine (p=0.033), and their survival was significantly better
      than patients with high RRM1 (p=0.001). In conclusion, RRM1 particularly in
      protein level is a reliable marker for gemcitabine resistance in BTC.
      Furthermore, qDFIHC is a useful method for the assessment of RRM1 protein, in
      order to design a tailor-made chemotherapeutic regimen for BTC patients.

PMID- 20811707
TI  - TC21 promotes cell motility and metastasis by regulating the expression of E
      cadherin and N-cadherin in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is an aggressive type of cancer, and it may be at
      an advanced stage when it is detected. It has been shown that TC21, a member of
      the Ras superfamily, is associated with the proliferation, migration and
      transformation of tumor cells. Previous studies have shown that TC21 is
      overexpressed in breast, esophageal and oral carcinomas, and that it is closely
      associated with the early stages of tumorigenesis. In this study, we demonstrate
      that TC21 overexpression promotes the motility of HCC cells in vitro and
      intrahepatic metastasis in vivo. Furthermore, experiments examining the effects
      of both the ectopic expression of TC21 and siRNA treatment in HCC cells showed
      that TC21 alters the expression of the adhesive molecules E-cadherin and N
      cadherin. Our data suggest that TC21 is associated with tumor progression and
      poor prognosis in HCC.

PMID- 20811708
TI  - Involvement of C12orf32 overexpression in breast carcinogenesis.
AB  - Through genome-wide gene expression profile analysis of breast cancer, we
      identified a gene, chromosome 12 open reading frame 32 (C12orf32), to be involved
      in mammary carcinogenesis. Semiquantitative RT-PCR and Northern blot analysis
      confirmed C12orf32 overexpression in breast cancer cells and its almost
      undetectable level of expression in normal human tissues. Immunocytochemical
      staining analysis using breast cancer cell lines revealed a cell cycle-dependent
      subcellular localization of endogenous C12orf32 protein. Depletion of C12orf32
      expression by small-hairpin RNA interference significantly suppressed the growth
      of breast cancer cell lines possibly due to the inhibition of G1/S transition and
      subsequent cell death. Western blot analysis indicated that a C12orf32 protein of
      35 kDa predicted from the cDNA sequences was processed to a 16-kDa protein of
      (C12orf32-p16) which was accumulated in most of breast cancer cell lines
      examined. Our data suggest that C12orf32 is a promising molecular target for the
      development of novel anticancer drugs such as peptide vaccines and siRNA drugs.

PMID- 20811709
TI  - Imatinib mesylate inhibits the proliferation-stimulating effect of human lung
      cancer-associated stromal fibroblasts on lung cancer cells.
AB  - Platelet-derived growth factor (PDGF) is a significant mediator in the
      proliferation of cancer-associated stromal fibroblasts (CAFs). The inhibition of
      CAF proliferation by blocking PDGF signaling could lead to a development of novel
      cancer therapy. We analyzed whether inhibiting proliferation of lung CAFs by
      imatinib mesylate, which has inhibitory activity on PDGF-receptor tyrosine
      kinase, could suppress the proliferative activity of lung cancer cells which
      coexisted in the tumor tissue. First, we established primary cultured fibroblasts
      from human lung cancer tissues. RT-PCR analysis showed that PDGF-receptors
      (PDGFRalpha and beta) were more highly expressed in the fibroblasts, whereas
      PDGFs (PDGF-A, and -B) were more in lung cancer cell lines. Western blotting
      showed that imatinib treatment inhibited phosphorylation of PDGFRbeta, Akt, and
      Erk1/2 in the fibroblasts. The treatment also significantly inhibited the
      proliferative activity of the fibroblasts. The inhibitory effects were exerted
      more definitely in co-administering imatinib and PDGF-BB, a dimer of the
      polypeptide chains of B, than in administering imatinib alone. The conditioned
      media of the fibroblasts significantly increased the proliferative activity of
      human lung cancer cell line A549 compared to control culture medium. The
      proliferation-stimulating effect on A549 cells decreased significantly in the
      conditioned media of the primary cultured fibroblasts that had been treated with
      imatinib. Our results suggest that imatinib has antitumor activity which is
      exerted by reducing the proliferation-stimulating effect of CAFs on lung cancer
      cells, as well as inhibiting the proliferation of CAFs, by way of blocking PDGF
      signaling.

PMID- 20811710
TI  - Vandetanib alters the protein pattern in malignant glioma and normal brain in the
      BT4C rat glioma model.
AB  - The treatment of glioblastoma is unsatisfactory. Improved understanding of the
      biological effects of treatment, together with development of new tools to
      predict outcome of the initiated treatment are therefore of great need.
      Vandetanib (ZD6474) is mainly a vascular endothelial growth factor (VEGF) and
      epidermal growth factor (EGF) receptor tyrosine kinase inhibitor. This study
      investigated the pattern of protein expression in brain tumor and normal brain
      tissue, following treatment with vandetanib in a rat glioma model. BT4C-cells
      were stereotactically implanted into the brain of BD IX rats. The rats were
      divided into three different experiments. The treatment schedule for experiments
      one and two consisted of daily, oral doses of vandetanib from day 6 until day 12
      or 20 after implantation, respectively. In the third experiment, each animal
      received a single dose of vandetanib on day 19 after implantation and was then
      sacrificed 2, 8 or 24 h thereafter. The protein expression profiles were analyzed
      by SELDI-TOF-MS and evaluated with multivariate statistical methods. Following
      treatment with vandetanib, we found significantly altered protein expression
      pattern in malignant glioma and normal brain. Analyzing protein spectra is an
      interesting option to assess biological effects induced in brain tissue by signal
      transduction inhibitors such as vandetanib.

PMID- 20811712
TI  - Medullary carcinoma of the large intestine: a population based analysis.
AB  - Medullary carcinoma (MC) of the colorectum is a relatively new histological type
      of adenocarcinoma characterized by poor glandular differentiation and
      intraepithelial lymphocytic infiltrate. To date, there has been no
      epidemiological study of this rare tumor type, which has now been incorporated as
      a separate entity in the World Health Organization (WHO) classification of
      colorectal cancers. We used the population-based registries of the Surveillance,
      Epidemiology and End Results (SEER) database to identify all cases of colorectal
      MC between 1973 and 2006 and compared them to poorly and undifferentiated colonic
      adenocarcinomas (PDA and UDA, respectively). We observed that MCs were rare
      tumors, constituting approximately 5-8 cases for every 10,000 colon cancers
      diagnosed, with a mean annual incidence of 3.47 (+/-0.75) per 10 million
      population. Mean age at diagnosis was 69.3 (+/-12.5) years, with incidence
      increasing with age. MCs were twice as common in females, who presented at a
      later age, with a lower stage and a trend towards favorable prognosis. MCs were
      extremely rare among African-Americans. MCs were most common in the proximal
      colon (74%), where they present at a later age than the sigmoid colon. There were
      no cases reliably identified in the rectum or appendix. Serum carcinoembryonic
      antigen levels (CEA) were elevated prior to first course of treatment in 40% of
      the patients. MCs were more commonly poorly differentiated (72%), with 22% being
      undifferentiated. MCs commonly presented with Stage II disease, with 10%
      presenting with metastases. Only one patient presented with N2b disease (>7
      positive nodes). Early outcome analyses showed that MCs have 1- and 2-year
      relative survival rates of 92.7 and 73.8% respectively. Although MCs showed a
      trend towards better early overall survival, undifferentiated MCs present more
      commonly with Stage III, with comparatively worse early outcomes.

PMID- 20811711
TI  - Blood monocytes from mammary tumor-bearing mice: early targets of tumor-induced
      immune suppression?
AB  - We have previously shown that peritoneal macrophages from mice bearing advanced
      D1-DMBA3 mammary tumors are impaired in their inflammatory functions but are not
      alternatively activated either and are less differentiated than the ones from
      normal mice. However, little is known about whether similar defects exist in
      their precursor stages as blood monocytes. We examined if blood monocytes from
      mammary tumor-bearing mice are already altered in their activation profiles
      before becoming macrophages and whether they correspond to inflammatory or
      resident monocyte subtypes. Much effort is currently devoted to reversing
      macrophage adverse traits in tumor hosts; as these cells reside within tissues,
      access is limited. Blood monocytes could be better targeted and manipulated by
      less invasive means. In the present study, mononuclear cells were isolated from
      whole blood of D1-DMBA-3 mammary tumor-bearing and normal BALB/c mice and
      CD115(+) monocytes were analyzed. Our results show that there is an increase in
      circulating monocytes in tumor hosts; these monocytes exhibit a reduced
      expression of several myeloid differentiation markers such as CD115, F4/80, CD68
      and CD11b. Moreover, downregulation of MHC II, CD62L and the proangiogenic marker
      Tie-2 are observed in these cells, whereas Gr-1 and Ly6C are upregulated.
      Furthermore, gene microarray analysis performed for the first time in blood
      monocytes from tumor hosts indicates that they express a mixture of pro
      inflammatory and anti-inflammatory cytokines and chemokines. Interestingly, CCR2
      and CX3CR1, which are crucial in monocyte definition as inflammatory or resident,
      respectively, are both upregulated. Importantly, complement proteins are enhanced
      whereas nitric oxide production is decreased and there is no measurable arginase
      activity detected in these cells. Collectively, our study represents the first
      comprehensive analysis of blood monocytes from tumor-bearing mice; we conclude
      that these cells are neither completely inflammatory nor suppressive and are less
      differentiated, similar to the macrophages they later become.

PMID- 20811713
TI  - Palladin, an actin-associated protein, is required for adherens junction
      formation and intercellular adhesion in HCT116 colorectal cancer cells.
AB  - Palladin is a scaffold protein involved in the formation of actin-associated
      protein complexes. Gene expression array analysis on the poorly metastatic HCT116
      colon cancer cell line and a metastatic derivative cell line (E1) with EMT
      (epithelial-mesenchymal transition) features showed a down-regulation of palladin
      gene expression in the latter. Knockdown of palladin expression in the HCT116
      cells suppressed junctional localization of E-cadherin, reduced intercellular
      adhesion and collective cell migration, showing that palladin plays an important
      role in maintaining the integrity of adherens junctions. The acquisition of the
      EMT features by the E1 cell line was dependent on the Erk pathway. Inhibition of
      this pathway by U0126 treatment in E1 cells resulted in the re-expression of
      palladin, relocalization of E-cadherin to the adherens junctions and a reversal
      of EMT features. The re-establishment of intercellular adhesion was dependent on
      palladin expression. The down-regulation of palladin was also observed in poorly
      differentiated tumor tubules and dissociated tumor cells that have undergone de
      differentiation in human primary colon tumors. Our data show that palladin is an
      integral component of adherens junctions and plays a role in the localization of
      E-cadherin to the junctions. The loss of palladin may be an integral part of EMT,
      an early step in the metastatic spread of colon carcinoma.

PMID- 20811714
TI  - Protective effect of the dopamine D(3) receptor agonist (7-OH-PIPAT) against
      apoptosis in malignant peripheral nerve sheath tumor (MPNST) cells.
AB  - Emerging evidence indicates that the dopamine D(3) receptor (D(3)R) mediates
      protective roles both in neuronal and non-neuronal cell lines. In a previous
      study we proposed that neurofibromin, a large tumor suppressor protein encoded by
      the neurofibromatosis type 1 gene (NF1), may increase susceptibility to apoptosis
      after serum deprivation in malignant peripheral nerve sheath tumor (MPNST) cells,
      thus acting as a proapoptotic gene. In addition, it has been observed that D(3)Rs
      are functionally correlated to neurofibromin. In this study, we examined whether
      7-OH-PIPAT, a potent dopamine D(3)R agonist, exerts an antiapoptotic role under
      the same culture conditions and then correlated this effect to changes in NF1
      expression. Results showed that serum deprivation caused a significant reduction
      of cell viability (MTT assay) both after 24 and 48 h (p<0.001). Treatment with
      increasing concentrations of 7-OH-PIPAT (10(-9)-10(-5) M) induced a progressive
      increase in cell viability both after 24 and 48 h as compared to vehicle-treated
      cells, with significant changes at the highest concentrations tested (10(-6) and
      10(-5) M). Consistently, at the latter two concentrations, a significant
      reduction in oligonucleosomes formation was observed, thus suggesting an
      antiapoptotic role of 7-OH-PIPAT. These results were confirmed by Hoechst 33254
      nuclear staining. To investigate whether these effects were correlated to changes
      in NF1 transcript and protein expression, quantitative real-time PCR, Western
      blot and immunofluorescence analyses were performed. Results demonstrated that
      the upregulation of NF1 transcripts and protein levels induced by serum
      withdrawal were remarkably attenuated by 10(-6) and 10(-5) M agonist treatment
      within 24 h (p<0.01 and p<0.001, respectively), whereas similar effects were
      observed already at a lower concentration (10(-7) M) after 48 h treatment
      (p<0.001). In conclusion, these results suggest that D(3)R might mediate the
      protective response to serum deprivation in MPNST cells through the inhibition of
      NF1 gene expression, further underlying a subtle role of these receptors in MPNST
      development.

PMID- 20811715
TI  - Anti-tumor activity of gene transfer of the membrane-stable CD40L mutant into
      lung cancer cells.
AB  - Gene transfer of CD40 ligand (CD40L) holds promise as a novel therapy for
      lymphoid malignancies and a number of solid carcinomas because of its multiple
      anti-tumor activities. However, membrane-bound CD40L can be cleaved into a
      soluble form, sCD40L, which contributes to systemic inflammatory and
      cardiovascular diseases, and induces survival signals in the absence of protein
      synthesis block, suggesting a deleterious side effect of CD40L gene therapy. We
      generated a plasmid encoding non-cleavable human CD40L mutant (pcDNA3.1+-CD40L-M)
      to determine the direct anti-proliferative and pro-apoptotic effects in CD40
      positive lung adenocarcinoma cell line A549, to verify activation of immature
      dentritic cells (DCs) by co-cultivation with the transfected A549 cells and to
      evaluate the lower expression of sCD40L relative to that of wild-type CD40L
      (CD40L-WT) transfectant in cell-free supernatants. These studies suggest that
      gene transfer of the membrane-stable CD40L mutant into CD40-positive cells may
      provide an efficient and safe method to treat non-small cell lung cancer.

PMID- 20811716
TI  - TrkB antibody elicits cytotoxicity and suppresses migration/invasion of
      transitional cell carcinoma cells.
AB  - BDNF (brain-derived neurotrophic factor) and its receptor TrkB (tropomyosin
      receptor kinase B) play important roles in the progression of cancer, including
      transitional cell carcinoma (TCC) cells reported in our previous investigation.
      In this study, we used a specific TrkB antibody (Ab) to evaluate its effects on
      survival, proliferation and migration/invasion in three TCC cell lines (BFTC905,
      T24 and TSGH8301) in vitro. The TrkB Ab at 1 and 3 microg/ml, but not the TrkA or
      TrkC Abs, significantly elicited cytotoxicity in TCC cells. The TrkB Ab at 3
      microg/ml also induced apoptosis of TCC cells, which may result from up
      regulation of phospho-p38 plus down-regulation of survivin and securin
      expression. The TrkB Ab at 0.5 microg/ml, which did not show cytotoxicity,
      suppressed migration of TCC cells and invasion of BFTC905 cells, possibly
      mediated through increased E-cadherin, decreased BDNF-stimulated phospho
      PLCgamma1 and reduced MMP-9 activity. These results indicate that TrkB blockade
      may be a new strategy for TCC therapy.

PMID- 20811717
TI  - P21-activated protein kinase 1 induces colorectal cancer metastasis involving ERK
      activation and phosphorylation of FAK at Ser-910.
AB  - Pak1 has been reported to be overexpressed in colorectal cancer, but the role of
      Pak1 in colorectal cancer remains unclear. In this study, Pak1 expression and
      activity were associated with aggressive behavior of colorectal cancer.
      Overexpression of Pak1 increased colorectal cancer cell motility and invasion,
      whereas down-regulation of Pak1 expression or activity reduced colorectal cancer
      cell migration and invasion. In addition, activated Pak1 inhibited stress fiber
      and focal adhesion complex formation in colorectal cancer cells and led to
      formation of motile phenotypes. Importantly, activated Pak1 elicited
      phosphorylation of FAK at Ser-910 via an ERK-dependent pathway in colorectal
      cancer cell lines and clinical samples. In conclusion, our results suggest that
      activated Pak1 regulates colorectal cancer metastasis requiring an ERK-dependent
      phosphorylation of FAK at Ser-910.

PMID- 20811718
TI  - Enhanced growth inhibition by combined DNA methylation/HDAC inhibitors in lung
      tumor cells with silenced CDKN2A.
AB  - Aberrant hypermethylation at CpG sites within the CDKN2A gene is associated with
      silencing and has been proposed as a target for reactivation using both DNA
      methylation and histone deacetylation inhibitors. This study investigates the
      role of selecting tumor samples with a silenced as compared to deleted CDKN2A
      locus when assessing the efficacy of DNA methyltransferase inhibitor, zebularine,
      combined with the HDAC inhibitor, depsipeptide. Non-small cell lung cancer cell
      lines with defined CDKN2A status were analyzed by MTS assay to determine the
      effect of zebularine or zebularine combined with depsipeptide on tumor cell
      growth. We observed that zebularine treatment resulted in inhibition of cell
      growth in 11 out of 12 lung cancer cell lines with silenced CDKN2A, but no cell
      growth inhibition was detected in the 7 lung cancer cell lines tested with
      deleted CDKN2A (p>0.001). In addition, we found that the combination of 30 microM
      zebularine and 6 or 7 nM depsipeptide resulted in a synergistic inhibition of
      cell growth in tumor cells with silenced CDKN2A (p<0.001, CI=0.70 and 0.57,
      respectively) but not in tumor cells with deleted CDKN2A. In conclusion, tumor
      cells with methylated CDKN2A are more sensitive to zebularine than cell lines
      with deleted CDKN2A and the combination of zebularine/depsipeptide results in a
      synergistic effect on cell growth inhibition that is also linked with the
      presence of silenced CDKN2A. Thus, combination of DNA methyltransferase and HDAC
      inhibitors may be a potential treatment for lung cancer patients, but careful
      selection of patients will be needed to optimize the benefit of this regimen.

PMID- 20811719
TI  - Acacia honey and chrysin reduce proliferation of melanoma cells through
      alterations in cell cycle progression.
AB  - Honey has long been used in medicine for different purposes. Only recently,
      however, its antioxidant property and preventive effects against different
      diseases, such as cancer, have been highlighted. Chrysin (5,7-dihydroxyflavone)
      is a natural flavone commonly found in acacia honey. It has previously been shown
      to be an anti-tumor agent. In this study, we investigated the antiproliferative
      role of honey or chrysin on human (A375) and murine (B16-F1) melanoma cell lines.
      The results of the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
      (MTT) assay and the trypan blue exclusion test showed that both the tested
      compounds were able to induce an antiproliferative effect on melanoma cells in a
      dose- and time-dependent manner. Flow cytometry analysis indicated that
      cytotoxicity induced by honey or chrysin was mediated by G(0)/G(1) cell cycle
      arrest and induction of hyperploid progression. Our results suggest that the anti
      proliferative effects of honey are due mainly to the presence of chrysin. Chrysin
      may therefore be considered a potential candidate for both cancer prevention and
      treatment. Further investigation is needed to validate the contribution of
      chrysin in tumor therapy in vivo.

PMID- 20811720
TI  - Biological effects of induced MYCN hyper-expression in MYCN-amplified
      neuroblastomas.
AB  - Neuroblastoma is a childhood malignancy of the sympathetic nervous system. The
      tumor exhibits two different phenotypes: favorable and unfavorable. MYCN
      amplification is associated with rapid tumor progression and the worst
      neuroblastoma disease outcome. We have previously reported that inhibitors of
      histone deacetylase (HDAC) and proteasome enhance favorable neuroblastoma gene
      expression in neuroblastoma cell lines and inhibit growth of these cells. In this
      study, we investigated the effect of trichostatin A or TSA (an HDAC inhibitor),
      and epoxomycin (a proteasome inhibitor) on MYCN and p53 expression in MYCN
      amplified neuroblastoma cells. It was found that TSA down-regulated MYCN
      expression, but Epoxomycin and the TSA/Epoxomycin combination led to MYCN hyper
      expression in MYCN-amplified neuroblastoma cell lines. Despite their contrasting
      effects on MYCN expression, TSA and Epoxomycin caused growth suppression and cell
      death of the MYCN-amplified cell lines examined. Consistent with these data,
      forced hyper-expression of MYCN in MYCN-amplified IMR5 cells via transfection
      resulted in growth suppression and the increased expression of several genes
      known to suppress growth or induce cell death. Furthermore, Epoxomycin as a
      single agent and its combination with TSA enhance p53 expression in the MYCN
      amplified neuroblastoma cell lines. Unexpectedly, co-transfection of TP53 and
      MYCN in IMR5 cells resulted in high p53 expression but a reduction of MYCN
      expression. Together our data suggest that either down regulation or hyper
      expression of MYCN results in growth inhibition and/or apoptosis of MYCN
      amplified neuroblastoma cells. In addition, elevated p53 expression has a
      suppressive effect on MYCN expression in these cells.

PMID- 20811721
TI  - Inhibitory effects of docosyl p-coumarate on DNA topoisomerase activity and human
      cancer cell growth.
AB  - We previously found six compounds of alkyl p-coumarates from a composite plant
      Artemisia annua L., and chemically synthesized these compounds (cis-isomer of
      C20, C22 and C24, and trans-isomer of C20, C22 and C24 of p-coumarates are
      compounds 1-6, respectively). This report describes the inhibitory activities of
      these alkyl p-coumarates against DNA polymerase (pol), DNA topoisomerase (topo),
      and human cancer cell growth. Among the compounds tested, compounds 1 and 4
      weakly inhibited repair-related pol beta activity, but no compound influenced the
      activity of replicative pol alpha. Compounds 4-6 and compounds 2 and 5 were
      potent inhibitors of human topos I and II, respectively. Compounds 2, 4, 5 and 6
      also suppressed the growth of human colon carcinoma cell line, HCT116, with or
      without p53, suggesting that cell growth inhibition had the same tendency as the
      inhibition of topos rather than pols. Compound 5 (docosyl p-coumarate), which was
      the strongest inhibitor of topo II and cancer cell growth in the compounds
      tested, halted HCT116 p53(+/+) cells in G2/M phases, and induced apoptosis,
      although this compound did not affect the cell cycle of HCT116 p53(-/-) cells.
      These results suggest that the effect of p53-dependent cell cycle arrest may be
      effective for topo inhibition by com-pound 5. From these findings, the action
      mode of alkyl p-coumarates as an anti-cancer agent is discussed.

PMID- 20811722
TI  - Effect of rapamycin, an mTOR inhibitor, on radiation sensitivity of lung cancer
      cells having different p53 gene status.
AB  - Activation to a large extent of the phosphatidylinositol 3-kinase (PI3K)/Akt
      pathway and mutations in the p53 gene are involved in lung cancer therapeutic
      resistance. The mammalian target of rapamycin (mTOR) acts as a downstream
      effector for Akt. Activation of the Akt/mTOR signal is a contributing factor to
      decreased radiation sensitivity. The purpose of this study was to examine whether
      the effect of rapamycin on radiation sensitivity is affected by cellular p53 gene
      status. Cellular radiation sensitivity was evaluated by using two human non-small
      cell lung cancer (NSCLC) cell lines with the same genetic background except for
      their p53 gene status (H1299/wtp53 and H1299/mp53). The cells were treated with
      rapamycin and/or radiation. Cell viability, cell proliferation, apoptosis, cell
      cycle and Akt/mTOR signaling activity were explored. Rapamycin synergistically
      enhanced the cytotoxicity of radiation, promoting the induction of apoptosis.
      Moreover, the combined treatment augmented the cytostatic effects of radiation
      regardless of cellular p53 gene status. Rapamycin in combination with radiation
      increased G1 arrest and suppressed progression to S phase in both cell lines.
      Furthermore, the combined treatment conduced to a prominent p53-independent down
      regulation of the mTOR signal and pro-survival molecule, cyclin D1. Rapamycin can
      enhance the effect of radiation through the repression of pro-survival signals
      and the reduction in the apoptotic threshold. Taken together, inhibition of the
      mTOR signal may be a promising strategy for radiosensitization with no relevance
      to p53 gene status from the aspects of cell lethality and cell growth depression.

PMID- 20811723
TI  - Resistance to chemotherapeutic agents and promotion of transforming activity
      mediated by embryonic stem cell-expressed Ras (ERas) signal in neuroblastoma
      cells.
AB  - Neuroblastoma is a common childhood tumor derived from neural crest precursor
      cells. In the present study, we investigated the expression and function of
      embryonic stem cell-expressed Ras (ERas), a novel Ras family protein previously
      reported as the specific expression gene in embryonic stem cells (ES cells), in
      neuroblastoma cell lines. Our results showed that the expressions of ERas were
      detected in neuroblastoma cell lines by RT-PCR and Western blotting. Therefore,
      we transfected a full length ERas expression vector into the neuroblastoma cell
      line SH-SY5Y, which has weak endogenous expression of ERas, and obtained clones
      with higher levels of expression. Overexpression of ERas did not increase the
      growth rate of the ERas transfectants but promoted their transforming activity.
      The ERas transfectants were more resistant to all the chemotherapy agents than
      the parental cell line. The ability of ERas to rescue cells from the toxic effect
      of chemotherapeutic agents was inhibited by the phosphatidylinositol 3'-kinase
      (PI3K) inhibitor PD294002. These results show that the ERas/PI3K pathway may
      provide resistance to chemotherapy and promote transforming activity in
      neuroblastoma.

PMID- 20811724
TI  - Death-associated protein kinase is essential for the survival of various types of
      uterine cancer cells.
AB  - We recently showed that targeted knockdown of death-associated protein kinase
      (DAPK) expression induces apoptosis in the human endometrial adenocarcinoma cell
      line HHUA. To investigate the possibility that DAPK may represent a molecular
      target for anticancer therapies for advanced uterine cancers, we examined the
      effects of DAPK siRNA transfections on the viability of five different human
      uterine cancer cell lines. The five uterine cell lines comprised three
      differentiated endometrial adenocarcinomas, one leiomyosarcoma and one
      carcinosarcoma. Cell death assays showed that the DAPK siRNA transfection
      significantly increased the cell death in all five uterine cancer cells examined.
      Ribonuclease protection assays did not show any remarkable changes in the bcl-2
      family gene expressions after the DAPK siRNA transfection in HHUA cells. Since
      DAPK-mutant mice were reported to be fertile and do not show lethality, DAPK may
      play a central role in the immortalization and carcinogenesis of uterine cancer
      cells, possibly without bcl-2 family-related apoptotic regulation. These results
      indicate that DAPK can be a convincing candidate for molecularly targeted
      anticancer therapies for patients with various types of advanced uterine cancers,
      including carcinosarcoma and leiomyosarcoma.

PMID- 20811725
TI  - 2-Arylthiazolidine-4-carboxylic acid amides (ATCAA) target dual pathways in
      cancer cells: 5'-AMP-activated protein kinase (AMPK)/mTOR and PI3K/Akt/mTOR
      pathways.
AB  - Phosphatidylinositol-3-kinase (PI3K)/Akt and 5'-AMP-activated protein kinase
      (AMPK) are attractive targets for anti-cancer drug development. Inhibition of Akt
      or activation of AMPK is cytotoxic to human cancer cells in vitro and in vivo. We
      previously demonstrated that 2-arylthiazolidine-4-carboxylic acid amides (ATCAA)
      are effective cytotoxic agents in prostate and melanoma cancer cell lines, with
      IC(50) values in the low/sub micromolar range. Using in vitro and in vivo
      studies, we further characterized the anti-cancer efficacy and mechanism of
      action of ATCAA-10, a potent lead. ATCAA-10 exhibited equal potency on both
      MES/SA and P-glycoprotein over-expressing multidrug resistant MES/SA/Dx5 cells,
      suggesting that ATCAA-10 may overcome multiple drug resistance. Cell-free kinase
      binding assays excluded the direct binding of ATCAA-10 to several kinases,
      including IGF-1R, EGFR, FGFR and PDGFR. However, in A549 and HeLa cells, ATCAA-10
      effectively dephosphorylated Akt, with concomitant phosphorylation of AMPK.
      Determination of intracellular ATP and AMP concentrations revealed that ATCAA-10
      activated AMPK by altering the intracellular AMP/ATP ratio. ATCAA-10 exhibited
      favorable pharmacokinetic properties in both mice and rats, including low
      clearance, low hepatic extraction rate, moderate volume of distribution and long
      half-life. In addition, ATCAA-10 inhibited A549 tumor xenograft growth with 46%
      tumor growth inhibition (TGI) at 20 mg/kg dose. Taken together; these results
      suggest that ATCAA-10 modulates the activity of two signaling pathways,
      PI3K/AKT/mTOR and AMPK/mTOR, resulting in the inhibition of cancer cell growth.

PMID- 20811726
TI  - Downregulation of active caspase 8 as a mechanism of acquired TRAIL resistance in
      mismatch repair-proficient colon carcinoma cell lines.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers the
      apoptotic cascade in various colon cancer cell lines after binding to the
      membrane receptors DR4 and DR5. However, not all cancer cell lines are sensitive
      to the therapeutic recombinant human TRAIL (rhTRAIL). To investigate the causes
      of TRAIL resistance in colon cancer cell lines, models have been developed,
      mostly in mismatch repair-deficient cells. These cells are prone to mutations in
      genes containing tandem repeat, including pro-apoptotic protein Bax. We therefore
      investigated the mechanism underlying TRAIL resistance acquisition in a mismatch
      repair-proficient colon carcinoma cell line. The TRAIL-resistant cell line SW948
      TR was established from the TRAIL-sensitive cell line SW948 by continuous
      exposure to rhTRAIL, and exhibited 140-fold less sensitivity to rhTRAIL in a cell
      viability assay. Resistance was stable for over a year in the absence of rhTRAIL.
      Both cell lines had similar TRAIL receptor cell membrane expression levels.
      Treatment with the protein synthesis inhibitor cycloheximide sensitized SW948-TR
      to rhTRAIL-induced apoptosis, indicating that the functionality of the TRAIL
      receptors was maintained. In SW948-TR, procaspase 8 protein levels but not mRNA
      levels were notably lower than in SW948. Downregulation of c-FLIP with short
      interfering RNA (siRNA) sensitized SW948-TR cells to rhTRAIL while caspase 8
      siRNA decreased rhTRAIL sensitivity in SW948, indicating the importance of the
      caspase 8/c-FLIP ratio. Proteasome inhibition with MG132 did not restore basic
      procaspase 8 levels but stabilized cleaved caspase 8 in rhTRAIL-treated SW948-TR
      cells. Altogether, our results suggest that colon cancer cells can acquire
      rhTRAIL resistance by primarily reducing the basal procaspase 8/c-FLIP ratio and
      by increasing active caspase 8 degradation after rhTRAIL treatment. Proteasome
      inhibitors can effectively overcome acquired rhTRAIL resistance in mismatch
      repair-proficient colon cancer cells.

PMID- 20811727
TI  - In vitro novel combinations of psychotropics and anti-cancer modalities in U87
      human glioblastoma cells.
AB  - Glioblastoma multiforme (GBM) is a highly aggressive malignant brain tumor.
      Despite some recent improvement in the treatment of this malignancy, life
      expectancy of GBM patients remains extremely low. Therefore, continuous efforts
      to develop new treatment modalities are mandatory. A novel approach to cancer
      treatment is the use of targeted treatments, alone and in combination with other
      therapies. In this study, we evaluated the effects of novel combinations of
      conventional anti-cancer treatments (temozolomide or irradiation) with the
      targeted drug, imatinib, or with psychotropic drugs, belonging to the selective
      serotonin reuptake inhibitors (SSRIs) and phenothiazine subclasses, as well as
      combination of imatinib with psychotropic agents, on a human U87 glioblastoma
      cell line. The combination of temozolomide with imatinib or the psychotropic
      drugs resulted in an additive anti-proliferative effect, while the combination of
      irradiation and the psychotropic agents resulted in a less than additive effect
      on cell proliferation. A marked synergistic anti-proliferative effect of imatinib
      combined with the psychotropic drugs fluoxetine, sertraline or perphenazine was
      demonstrated. None of the single or combined treatments led to a reduction in the
      expression of phosphorylated MAP kinase. However, a marked synergistic reduction
      in the expression of the key regulatory molecule, pAKT, was detected, following
      the combined treatment of the cells with the imatinib/psychotropics combination.
      This down-regulation of pAKT may mediate the synergistic anti-proliferative
      interaction of imatinib with the psychotropic agents. Although the concentrations
      of the psychotropic agents used in this and other in vitro studies were beyond
      the clinically relevant blood levels in humans, recent studies have demonstrated
      anti-proliferative effects in vivo, using sertraline in a human colon cancer
      model. Thus, it seems that further in vivo studies combining imatinib with
      psychotropic agents, especially fluoxetine and sertraline, are warranted.

PMID- 20811728
TI  - [Current developments in xenon research. Importance for anesthesia and intensive
      care medicine].
AB  - The noble gas xenon exerts favorable anesthetic properties along with remarkable
      hemodynamic stability in healthy patients undergoing elective surgery. It
      represents the nearly ideal anesthetic and provides safe and well controllable
      anesthesia although the exact mechanism by which xenon produces anesthesia
      remains to be elucidated. In addition xenon offers organ protective properties
      for vital organs including the brain, heart and kidneys which seem to be
      synergistic when used in combination with therapeutic hypothermia. As the high
      cost of xenon will probably preclude its wider use as a routine anesthetic, data
      from extensive tests in large numbers of high risk patients is needed to confirm
      its possible superiority in this setting.

PMID- 20811729
TI  - [Regional anesthesia and neurological diseases].
AB  - Modern anesthesia is handling an increasing number of patients with neurological
      diseases who require narcosis. Regional anesthesia techniques offer qualities
      which might be advantageous for this group particularly for childbirth. The
      number of pregnant women with neurological diseases has increased significantly
      in the recent years due to improved diagnostics and therapy. A more careful
      approach to regional anesthesia in patients with neurological diseases is
      necessary as the drugs themselves possess neurotoxic effects and the procedure
      might worsen the underlying neurological diseases. Additionally, performing
      regional anesthesia might be more complicated and the resulting blockade might be
      different from the expected neuronal block. Published data concerning regional
      anesthesia in this patient group are limited and mainly restricted to case
      reports. In this review general considerations regarding regional anesthesia,
      techniques, drugs and methods in these patient groups will be discussed. In the
      second part the practical approach to regional anesthesia for some of the most
      important neurological diseases is highlighted.

PMID- 20811730
TI  - [The quality of university teaching in psychiatry and psychotherapy: results of a
      survey on the current status following the introduction of the new medical
      accreditation system].
AB  - The classic criticism levelled at German medical studies was addressed in 2002
      with the reform of the German medical accreditation system. For the specialties
      Psychiatry and Psychotherapy, a national workshop of the German Society for
      Psychiatry, Psychotherapy and Neurology (DGPPN) was held in Heidelberg on
      23.01.2004 to implement the new legal requirements for teaching. In 2008, a
      postal survey was conducted among the 36 German medical faculties by the DGPPN to
      establish the current status of the proposed implementation, with the general
      structure of undergraduate medical training, student-centered syllabuses and the
      general significance of teaching forming the main points. With a response rate of
      75%, the results can be considered representative. In general, a cautiously
      positive conclusion can be drawn on the implementation of the medical
      accreditation system. Having said that, it should be borne in mind that
      implementation is not yet complete and still requires optimization, for example
      in terms of making examinations not only theoretical but also more practical in
      approach.

PMID- 20811731
TI  - [Vascular dementia].
AB  - Vascular dementia (VaD) constitutes the second most frequent cause of dementia
      following Alzheimer's disease (AD). In contrast to AD, VaD encompasses a variety
      of conditions and dementia mechanisms including multiple and strategic infarcts,
      widespread white matter lesions and hemorrhages. The diagnosis of VaD is based on
      the patient history, the clinical evaluation and neuroimaging. Treatment of VaD
      should account for the underlying vascular condition and is directed towards the
      control of vascular risk factors and stroke prevention. The need for early
      diagnosis and preventive treatment has promoted the concept of vascular cognitive
      impairment (VCI). Harmonization standards for the description and study of VCI
      have recently been published. A common and distinct subtype of VaD is subcortical
      ischemic vascular dementia (SIVD) which is related to cerebral small vessel
      disease. SIVD is clinically characterized by impairment of executive functions
      and processing speed with relatively preserved memory. Cerebral autosomal
      dominant arteriopathy with subcortical infarcts and leukoencephalopathy
      (CADASIL), a genetic variant of SIVD, represents an important differential
      diagnosis and may serve as a model of SIVD.

PMID- 20811733
TI  - Mucoid degeneration of the anterior cruciate ligament: MRI, clinical,
      intraoperative, and histological findings.
AB  - PURPOSE: To describe the clinical, MRI, intraoperative, and histological features
      of mucoid degeneration of the anterior cruciate ligament (ACL). METHODS: This
      study included 10 patients (average age 47 years, range 19-69 years) who
      underwent surgery due to clinical diagnoses of mucoid degeneration of the ACL.
      All patients underwent preoperative magnetic resonance imaging (MRI) and were
      arthroscopically treated. RESULTS: All 10 patients reported preoperative
      posterior knee pain. MRI indicated a thickened ACL with increased signal on all
      sequences. Postoperatively, only six of 10 patients were confirmed by biopsy to
      have a mucoid degeneration of the ACL. An associated intraosseous tibial cyst or
      ganglion was observed only in patients with a definitive diagnosis of mucoid
      degeneration. CONCLUSIONS: Mucoid degeneration of the ACL can be suspected in
      patients with posterior knee pain associated with a thickened ACL. Associated
      findings such as an intraosseous tibial or ganglion cyst help to rule out
      differential diagnosis.

PMID- 20811732
TI  - Minimally invasive total knee arthroplasty: comparison of jig-based technique
      versus computer navigation for clinical and alignment outcome.
AB  - PURPOSE: Correct alignment of the leg and positioning of the components are
      important factors in good long-term outcome of total knee arthroplasty (TKA).
      Computer-assisted navigation systems were introduced to improve component
      alignment accuracies. The three main hypotheses of this study were that the
      navigated compared to jig-based patient will show the following: (1) No
      difference in clinical outcomes. (2) Better alignment in the frontal and sagittal
      plane. (3) Better rotational positioning of components. METHODS: The authors
      evaluated 100 patients who had minimally invasive TKA using either an image-free
      computer-assisted navigation system (n=50) or a jig-based technique (n=50). Six
      months postoperatively, clinical and radiological evaluations were performed
      using full-length standing anteroposterior and lateral radiographs and CT scans
      of the knee. RESULTS: Knee Society knee score, function score, and range of
      motion were comparable in the two groups after surgery. The percentage of
      patients with a frontal tibiofemoral angle within +/-3 degrees  of the ideal was
      significantly higher in the navigated group than in the jig-based group (94% vs.
      78%, respectively; P=0.041). No significant differences were found between groups
      in terms of the frontal and sagittal planes as well as rotational alignment of
      the femoral or tibial components. CONCLUSION: Computer-assisted TKA gives a
      better correction of alignment of the leg compared with jig-based TKA when
      combined with a minimally invasive surgical approach.

PMID- 20811734
TI  - Graft length change and radiographic assessment of femoral drill hole position
      for medial patellofemoral ligament reconstruction.
AB  - PURPOSE: Medial patellofemoral ligament (MPFL) reconstruction has been recognized
      as a useful treatment method for patella instability. However, the optimal
      fixation site has not been well investigated, and few reports have examined
      intraoperative graft length change. The purpose of the study is to evaluate the
      intraoperative graft length change and femoral drill hole position to find the
      optimal graft placement. METHODS: The graft length change between the two points
      on patella and femur was measured using Isotac((r)) and Isometric Positioner((r))
      during passive knee motion in 27 cases of MPFL. The location of Isotac((r)) was
      also evaluated on the 2-directional radiograph. The pre- and postoperative
      radiographic assessments have been done in order to evaluate the effect of MPFL
      reconstruction on patellofemoral alignment. RESULTS: There were 10 cases in which
      the distance between the two points became longer during knee flexion, 8 cases in
      which it became shorter and the remaining 9 cases in which the distance changed
      within 2 mm. The femoral drill hole position was assessed assuming that the
      maximum anterior-posterior (AP) diameter of the femur on the lateral radiograph
      was defined as 100%. The distance of the femoral tunnel position from the
      articular surface averaged 50% overall, 46% in the short group, 55% in the longer
      group and 48% in the isometric group (P < 0.001). Patella height seemingly
      affected the length change character. The intraoperative length change influenced
      the early recovery of knee range motion postoperatively. CONCLUSIONS: The femoral
      tunnel position is reaffirmed to be an essential determinant for the graft length
      change in the MPFL reconstruction. Both graft length change measurements and
      intraoperative radiographic assessment are practical for proper graft placement.

PMID- 20811735
TI  - Dysfunction of the posterior cruciate ligament in total knee arthroplasty.
AB  - PURPOSE: Total knee arthroplasty (TKA) is typically carried out either with
      retention (CR) of the posterior cruciate ligament (PCL) or with sacrifice of this
      ligament and implantation of a posterior stabilised (PS) prosthesis. This paper
      investigates a comparison of PCL function in knees treated for osteoarthritis
      with TKA where the PCL is preserved to those knees treated with TKA and posterior
      stabilisation. METHODS: One hundred and sixty-eight patients (232 knees) who had
      undergone TKA with either a PS or CR implant were included in the study. Clinical
      assessment included antero-posterior (AP) laxity and posterior sag assessment
      with an arthrometer. RESULTS: The mean AP laxity at 90 degrees  of flexion for CR
      TKAs was 6.5 mm (+/-3.1) and was the same [6.5 mm (+/-2.4)] as in the PS group.
      However, 56% of the PCL-preserved knees had a posterior sag of over 3 mm compared
      to 18% of the knees in the PS group. The American Knee Society Scores for either
      group showed that, although the mean function score was the same, the knee score
      was superior in the PS group (77 vs. 84). The range of motion was also superior
      in the PS group (111 degrees  vs. 105 degrees ). CONCLUSION: The use of the PS
      prosthesis for TKA provides a more predictable outcome with regard to posterior
      sag and a better maximum flexion than a CR implant.

PMID- 20811736
TI  - Navigated intra-articular ACL reconstruction with additional extra-articular
      tenodesis using the same hamstring graft.
AB  - PURPOSE: In some complex cases, standard anterior cruciate ligament
      reconstruction is not enough and could lead to a new failure. Lateral extra
      articular reconstruction should be added. We describe a new mini-invasive
      technique using the same hamstring graft for intra-articular reconstruction and
      lateral tenodesis, optimized with navigation. METHOD: This arthroscopic technique
      is precisely described, different graft setting are possible, four strands graft
      inside the joint and two strands for the tenodesis or two strands graft for all
      the whole graft. As the lateral tenodesis is not anatomic, tunnel placement could
      be tricky. The use of navigation system is a real advantage for this technique
      with optimal tunnels placement. RESULTS: No results are given. CONCLUSION: This
      technique is comparable to others reported previously, showing a clinical
      advantage and no increasing of osteoarthritis. The use of the same graft avoids
      collateral damages, and navigation improves the graft placement.

PMID- 20811738
TI  - Moclobemide exerts anti-inflammatory effect in lipopolysaccharide-activated
      primary mixed glial cell culture.
AB  - An increasing body of evidence indicates that glial activation and
      neuroinflammation play an important role in the pathogenesis of psychiatric and
      neurodegenerative diseases. Activated glial cells secrete various cytokines that
      influence neurotransmission, hypothalamus-pituitary-adrenal axis activity,
      neuronal plasticity and neurogenesis. It has been suggested that alterations in
      cytokine networks are involved in the mechanism of action of antidepressant
      drugs. Until now, only a few studies demonstrated that some tricyclic
      antidepressants and selective serotonin reuptake inhibitors reduced production of
      pro-inflammatory cytokines in brain glia cells. We have investigated for the
      first time whether the antidepressant, moclobemide (a reversible selective
      inhibitor of monoamine oxidase-A) has an influence on pro-inflammatory cytokines
      [interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha] and anti
      inflammatory cytokine (IL-10) in primary rat mixed glial cell cultures stimulated
      by lipopolysaccharide (LPS). Our results showed that moclobemide used in a wide
      range of concentrations diminished LPS-stimulated IL-1beta and TNF-alpha mRNAs
      expression in cellular extracts and remarkably reduced the levels of both pro
      inflammatory cytokines in culture medium. In opposite to this, the drug had no
      influence on IL-10 mRNA and slightly reduced IL-10 concentration. Moreover,
      moclobemide decreased LPS-stimulated translocation of NFkappaB p65 subunit into
      cellular nuclei. These results suggest that moclobemide exerts anti-inflammatory
      effect in the central nervous system because it affects the balance between pro-
      and anti-inflammatory cytokines (IL-1beta, TNF-alpha/IL-10) in primary mixed
      glial cell cultures.

PMID- 20811739
TI  - Further application of size-exclusion chromatography combined with small-angle X
      ray scattering optics for characterization of biological macromolecules.
AB  - Size-exclusion chromatography (gel filtration chromatography or gel permeation
      chromatography) in conjunction with online synchrotron radiation solution small
      angle X-ray scattering optics, absorbance, and/or refractive index detectors was
      further assessed by application of biological macromolecules, such as the hollow
      sphere protein complex, apoferritin, and a linear polysaccharide, pullulan. The
      net X-ray scattering patterns of the eluted 24-mer molecule of apoferritin showed
      the specific character for the hollow spherical shape. The chromatographic (time
      resolved) X-ray scattering data of the linear polysaccharide pullulan revealed
      the flexible chain structure during the chromatographic separation in an aqueous
      solution. These further applications demonstrated that the present measurement
      technique will be useful for not only the determination of the radius of gyration
      value of less than about 10 nm and molecular weight below several hundred
      thousand but also for the structural characterization of the various
      macromolecules during the chromatography.

PMID- 20811740
TI  - Analysis of polyfluorinated compounds in foods.
AB  - Polyfluorinated compounds (PFCs) are a relatively new and diverse set of
      compounds analyzed as contaminants in food. Their unique physical-chemical
      properties dictate the methods used for their analysis. Current analyses of the
      more volatile PFCs involve gas chromatography-mass spectrometry; liquid
      chromatography-tandem mass spectrometry is generally used for the less volatile
      PFCs. Considerations in the analysis of PFCs in foods include contamination from
      the widespread presence of materials that contain various PFCs, endogenous
      interfering compounds, and matrix effects. Future opportunities for research on
      PFCs in food exist, particularly in the areas of biological molecule-PFC
      interactions and the effects of food processing on these interactions. Future
      research will be facilitated by the synthesis of a wider variety of analytical
      standards.

PMID- 20811743
TI  - Real-time ultrasound-aided central vein cannulation failure rate: establishing a
      benchmark.
AB  - BACKGROUND: The use of real-time two-dimensional B-mode ultrasound (RTUS)-aided
      central venous access device (CVAD) insertion has been recommended by health-care
      agencies, but a realistic failure rate for bedside attempts is unknown. METHODS:
      The failure rate of RTUS-aided CVAD insertion is estimated using data from adult
      inpatients and outpatients referred to a tertiary referral radiology department
      for a new CVAD insertion during the 2.5-year period ending February 29, 2008.
      Cannulation failure, complications, and additional fluoroscopic interventions per
      central vein cannulation attempt and per patient encounter were retrospectively
      collected and evaluated. RESULTS: Of the 2456 consecutive patient encounters, the
      index central vein cannulation failure rate using only RTUS and fluoroscopy was
      4.8%; ultimate failure rate was 0.3%. The procedural mortality rate was 0.04%. If
      the index upper-body central vein cannulation failed, an ipsilateral upper-body
      attempt through a different central vein failed in 63.6%, whereas a contralateral
      upper-body attempt failed in 26.7% (p = 0.11) and a common femoral vein attempt
      failed in 11.5% (p = 0.0039). CONCLUSIONS: The minimum bedside failure rate of
      RTUS-aided CVAD insertion is 4.8% for the index central vein cannulated. The
      ultimate failure rate of 0.3% and the mortality rate of 0.04% are due to RTUS,
      fluoroscopy, and the additional equipment available in an IR suite. If the upper
      body index central vein cannulation fails, cannulation of the common femoral vein
      is more likely to succeed than additional attempts in other ipsilateral upper
      body central veins.

PMID- 20811742
TI  - The impact of biofumigation and chemical fumigation methods on the structure and
      function of the soil microbial community.
AB  - Biofumigation (BIOF) is carried out mainly by the incorporation of brassica plant
      parts into the soil, and this fumigation activity has been linked to their high
      glucosinolate (GSL) content. GSLs are hydrolyzed by the endogenous enzyme
      myrosinase to release isothiocyanates (ITCs). A microcosm study was conducted to
      investigate the effects induced on the soil microbial community by the
      incorporation of broccoli residues into soil either with (BM) or without (B)
      added myrosinase and of chemical fumigation, either as soil application of 2
      phenylethyl ITC (PITC) or metham sodium (MS). Soil microbial activity was
      evaluated by measuring fluorescein diacetate hydrolysis and soil respiration.
      Effects on the structure of the total microbial community were assessed by
      phospholipid fatty acid analysis, while the impact on important fungal
      (ascomycetes (ASC)) and bacterial (ammonia-oxidizing bacteria (AOB)) guilds was
      evaluated by denaturating gradient gel electrophoresis (DGGE). Overall, B, and to
      a lesser extent BM, stimulated microbial activity and biomass. The diminished
      effect of BM compared to B was particularly evident in fungi and Gram-negative
      bacteria and was attributed to rapid ITC release following the myrosinase
      treatment. PITC did not have a significant effect, whereas an inhibitory effect
      was observed in the MS-treated soil. DGGE analysis showed that the ASC community
      was temporarily altered by BIOF treatments and more persistently by the MS
      treatment, while the structure of the AOB community was not affected by the
      treatments. Cloning of the ASC community showed that MS application had a
      deleterious effect on potential plant pathogens like Fusarium, Nectria, and
      Cladosporium compared to BIOF treatments which did not appear to inhibit them.
      Our findings indicate that BIOF induces changes on the structure and function of
      the soil microbial community that are mostly related to microbial substrate
      availability changes derived from the soil amendment with fresh organic
      materials.

PMID- 20811744
TI  - Surgical decision-making in immediate breast reconstruction.
AB  - BACKGROUND: Immediate breast reconstruction has been accepted as safe and
      practical after mastectomy for breast cancer; factors limiting its use are
      patient comorbidities and potential complications caused by adjuvant therapies
      (particularly radiotherapy). The aim of this study was to identify factors
      considered by surgeons when deciding whether to offer immediate breast
      reconstruction, to determine the surgeon's accuracy when predicting
      postmastectomy radiotherapy, and to assess the impact of premastectomy
      investigations on decision-making. METHODS: Four oncoplastic breast surgeons
      completed a survey for every mastectomy performed over an 11-month period. On the
      survey form they indicated reason for mastectomy, investigations available
      premastectomy, if they offered immediate reconstruction, and if not offered, why
      they did not offer it. Data on adjuvant therapies employed was also collected.
      RESULTS: A total of 157 women underwent mastectomy during the study period.
      Seventy-six (48.4%) were offered immediate reconstruction and 36 (22.9%)
      accepted. The most common reason for not offering immediate reconstruction was
      the predicted need for postmastectomy radiotherapy (56.8%). Of the 76 patients
      offered immediate reconstruction, 9 went onto be offered postmastectomy
      radiotherapy (11.8%). Decision-making was no more accurate in those women who had
      MRI, axillary staging, or excisional pathology available premastectomy.
      CONCLUSIONS: The most common reason for not offering immediate breast
      reconstruction is the need for postmastectomy radiotherapy and surgeons are able
      to predict this accurately. The addition of invasive and expensive staging
      investigations premastectomy does not appear to assist this decision-making
      process. Despite careful patient selection, a high rate of immediate
      reconstruction may be maintained.

PMID- 20811745
TI  - External validation of modified EuroSCORE.
AB  - BACKGROUND: EuroSCORE is an adult cardiac surgery risk scoring method that is
      used worldwide, which has been shown to significantly overestimate the operative
      risk. We derived a new risk scoring method by modifying some of the risk factors
      included in the EuroSCORE algorithm and we validated it in an external database.
      METHODS: This study included 4,014 patients who underwent adult cardiac surgery
      at the Heart Centre, Tampere University Hospital, Finland. Operative risk was
      estimated by EuroSCORE and its modified version. RESULTS: In-hospital
      postoperative mortality rate was 3.2%. EuroSCORE (AUC for logistic EuroSCORE
      0.82; 95% confidence interval (CI), 0.79-0.85) and modified score (AUC for
      logistic modified score 0.79; 95% CI, 0.75-0.83) performed well in predicting in
      hospital mortality in this series. The mean logistic EuroSCORE was 8%, and the
      mean logistic modified score was 2.2%. Thus, the observed to expected ratio for
      in-hospital mortality was 0.4 for logistic EuroSCORE and 1.5 for logistic
      modified score. The difference between observed and predicted mortality rate
      matched correctly for increasing additive modified score, but not for EuroSCORE.
      The observed to predicted ratio in high-risk patients (within the 90th percentile
      of each risk algorithm) was 0.36 (13.2%/36.2% in 402 patients) for logistic
      EuroSCORE and 0.99 (14.7%/14.9% in 395 patients) for logistic modified score.
      CONCLUSIONS: This modified and simplified score, which includes most of EuroSCORE
      variables, seems to provide a more realistic estimation of postoperative
      mortality risk of patients undergoing any adult cardiac surgery.

PMID- 20811747
TI  - Pancreaticobiliary reflux in patients with and without cholelithiasis: is it a
      normal phenomenon?
AB  - BACKGROUND: Pancreaticobiliary reflux is a pathologic phenomenon occurring in
      patients with gallstones. However, the occurrence of pancreaticobiliary reflux
      has not been studied in patients without gallstones. The objective of the present
      study was to measure the bile levels of amylase and lipase in patients without
      gallstones submitted to cholecystectomy as part of another surgical procedure,
      and to compare these values with the bile levels of amylase and lipase of
      patients submitted to cholecystectomy for gallstone disease. PATIENTS AND
      METHODS: A prospective observational and comparative study was designed. A sample
      of 136 consecutive patients was included. Amylase and lipase levels were measured
      in bile. At our institution, normal plasma concentrations of amylase are 28-100
      IU/l and lipase 13-60 IU/l. Normal values for pancreatic enzyme concentrations in
      bile have not been established. Therefore, bile amylase and lipase concentrations
      exceeding normal plasma concentrations were deemed to be elevated. RESULTS: Of
      the patients in the present study, 103 (76%) had gallstones and 33 (24%) had
      healthy gallbladders without gallstones. According to normal plasma levels for
      amylase and lipase, these enzymes in bile were elevated in 83.5% patients with
      gallstones, compared to elevated levels of amylase in 6% patients and lipase in
      3% patients without gallstones (P < 0.0001). CONCLUSIONS: Pancreaticobiliary
      reflux is a common phenomenon in patients with gallstones and an uncommon
      phenomenon in patients with healthy gallbladders without gallstone disease.

PMID- 20811746
TI  - Human fibrinogen patches application reduces intra-abdominal infectious
      complications in pancreas transplant with enteric drainage.
AB  - PURPOSE: The purpose of the study was to analyze the incidence of intra-abdominal
      infectious complications after the application of a fibrinogen sealant to the
      duodenojejunal anastomosis in simultaneous pancreas-kidney transplants (SPK) with
      enteric drainage. METHODS: Results of 68 SPKs with enteric drainage were
      prospectively assessed. A fibrinogen and thrombin sheet was applied to the
      duodenojejunal anastomosis in 34 patients, who were compared to a control group
      of 34 patients. The incidence and severity of intra-abdominal infectious
      complications and the 1-year patient and grafts survival were analyzed. RESULTS:
      Eighteen patients experienced intra-abdominal infectious complications. Grade 1a
      complications occurred in the study group, whereas surgery was required only in
      patients from the control group: complications grade 3a (15%) and complications
      grade 3b (18%) (p = 0.003 vs. study group, respectively). The overall rate of
      anastomotic leakage (complications grade 2b and 3b) was 10%, all of which
      occurred in the control group. The length of hospital stay was higher in the
      control group was 34.6 +/- 11.3 days vs. 22.8 +/- 11.1 days (p = 0.03). There
      were no significant differences in 1-year patient and graft survival between
      groups. CONCLUSIONS: In our study, the application of fibrinogen and thrombin
      sheets was associated to a decrease in the number and severity of intra-abdominal
      infectious complications.

PMID- 20811748
TI  - Current trends and short-term outcomes of live donor nephrectomy: a population
      based analysis of the nationwide inpatient sample.
AB  - BACKGROUND: Recent United Network for Organ Sharing (UNOS) data suggest that live
      kidney donation is stagnant. Current practices and trends in laparoscopic donor
      nephrectomy (LDN) among the transplant community remain largely unknown.
      MATERIALS AND METHODS: From the Nationwide Inpatient Sample (NIS) from 1998 to
      2006, patients undergoing LDN (n = 9,437) were identified. RESULTS: Live kidney
      donation in the United States did not show an increase in the NIS. Of the live
      donor cases recorded, 58 (0.61%) were associated with a major short-term
      complication. The number of LDNs performed by transplant surgeons decreased over
      the study period from 76.5% in 1998 to 30.4% in 2006. CONCLUSIONS: In the United
      Stares, LDNs are performed safely with a low short-term complication rate.
      Despite the use of laparoscopy and the increased need of donor organs, the rate
      of LDN in kidney transplantation has not increased proportionally.

PMID- 20811749
TI  - [Therapeutic dosage in half bridging?].

PMID- 20811750
TI  - [Chance for young electrophysiologists: the continuing education program
      "Fellowship heart rhythm"].
AB  - Increasing workloads, growing economical pressure and developments on the German
      job market for young physicians create a background which threatens an adequate
      education and training of physicians in many places. The"Fellowship heart rhythm"
      program focuses on training in clinical electrophysiology complementary to
      established educational initiatives, such as courses for competence in pacemaker
      and ICD therapy of the German Cardiac Society. Participants have to be residents
      with a minimum of 3 years clinical experience and should be younger than 36 years
      old. They should be actively involved with a long-term perspective in clinical
      electrophysiology. Activity in the fields of pacing, defibrillator and cardiac
      resynchronization therapy is required. The hospital has to be able provide the
      possibility of invasive electrophysiology and catheter ablation including a 3
      dimensional mapping system. In 6 face-to-face meetings of 3 days each, the state
      of the art is presented in the topics electrophysiological studies, sudden
      cardiac death and defibrillation, health economy/management, catheter ablation,
      atrial fibrillation and heart failure and arrhythmias. The first 4 years with 2
      fellowship programs have demonstrated that this project enables education at a
      high level, strongly supporting advances in scientific interest, individual
      development and medical orientation. The fellowship program facilitates the
      development of a network of young electrophysiologists in Germany.

PMID- 20811751
TI  - Over-expression of an FT-homologous gene of apple induces early flowering in
      annual and perennial plants.
AB  - The protein encoded by the FLOWERING LOCUS T (FT) gene from Arabidopsis thaliana
      seems to be the long-searched florigen, and over-expression of FT orthologues
      resulted in accelerated flower development in annual and perennial plants. In the
      present study, we isolated two allelic mRNA sequences of an FT-homologous gene
      from apple, which was designated as MdFT1. Using a SSR motif this gene was mapped
      on LG 12 of apple. Over-expression of MdFT1 in Arabidopsis and the commercially
      important tree species poplar and apple itself using the CaMV 35S or the
      Arabidopsis Suc2 promoter resulted in significant accelerated flowering compared
      with wild-type plants. Transgenic T(0) plants of Arabidopsis flowered 4-6 days on
      average earlier than wild-type Arabidopsis under LD conditions. Under short-day
      conditions Suc2::MdFT1 plants of the T(1)-generation flowered after 66 +/- 18
      days, while wild-type plants flowered about 22 days later. All transgenic
      Arabidopsis plants showed a normal habit except for the early flowering
      phenotype. Early flowering was detected 6-10 months after transformation in
      transgenic polar clones containing MdFT1 driven by the CaMV 35S, whereas plants
      of the transgenic apple clone T780 set up its first flowers during in vitro
      cultivation. Based on our results we conclude that MdFT1 is responsible for
      inducing flowering and that the function of the apple FT1 gene is conserved in
      annual herbaceous species as well as perennial woody species. Furthermore, we
      discuss the role of MdFT1 in flower development with regard to the findings of
      genetic studies on apple.

PMID- 20811752
TI  - [Chronic pain patients and their expectations towards physician care. Results
      from the Austrian Patient Report].
AB  - BACKGROUND: The Austrian Patient Report illustrates the preferences of Austrian
      chronic disease patients for the first time. MATERIAL AND METHODS: A
      standardised, self-administered questionnaire was used with items in the fields
      of general information, information flow, medicine and health, social and
      societal aspects and statistics. RESULTS: The most important item for Austrian
      chronic pain patients is a comprehensive discussion with their physician, which
      is even more important than a reduction in pain intensity. CONCLUSIONS: More
      efforts have to be made to educate and inform chronic pain patients adequately
      from the doctor's side.

PMID- 20811753
TI  - Cardiovascular and gastrointestinal events of three antiplatelet therapies:
      clopidogrel, clopidogrel plus proton-pump inhibitors, and aspirin plus proton
      pump inhibitors in patients with previous gastrointestinal bleeding.
AB  - BACKGROUND: Concomitant use of antiplatelet agents and proton-pump inhibitors
      (PPIs) has been recommended in patients with a history of gastrointestinal (GI)
      hemorrhage. However, recent studies have reported that PPIs may alter
      clopidogrel's pharmacokinetics and potentially lead to an increased risk of
      recurrent adverse cardiovascular (CV) events. METHODS: Using Taiwan's 2000-2006
      National Health Insurance database, this population-based retrospective cohort
      study assessed CV and GI events in patients who had a prior history of GI
      bleeding and had been prescribed ongoing antiplatelet therapy after acute
      coronary syndrome (ACS) discharge. We identified 3,580 ACS patients and
      categorized them into (1) those taking clopidogrel alone, (2) those taking
      clopidogrel plus PPIs, and (3) those taking aspirin plus PPIs. Cox proportional
      hazards models were used to assess the association between the use of
      antiplatelet therapies and CV/GI events. RESULTS: The clopidogrel only group and
      the clopidogrel plus PPI group were found to be at lower risk for GI events than
      the aspirin plus PPI group [adjusted hazard ratio (HR) 0.23 (95% confidence
      interval; CI 0.14-0.36) and HR 0.70 (0.52-0.96), respectively]. However, while
      the clopidogrel only group had a lower risk of CV events than the aspirin plus
      PPI group [HR 0.57 (0.38-0.84)], the clopidogrel plus PPI group had a
      significantly higher CV risk than the aspirin plus PPI group [HR 1.59 (1.18
      2.13)]. CONCLUSIONS: Our findings suggest that although the use of clopidogrel
      plus PPIs provides GI benefits, with this treatment, there is an increased CV
      risk among patients with a history of GI bleeding.

PMID- 20811755
TI  - Changes of concave and convex rib-vertebral angle, angle difference and angle
      ratio in patients with right thoracic adolescent idiopathic scoliosis.
AB  - The aim of this study is to describe the radiological changes in rib-vertebral
      angles (RVAs), rib-vertebral angle differences (RVADs), and rib-vertebral angle
      ratios (RVARas) in patients with untreated right thoracic adolescent idiopathic
      scoliosis and to compare with the normal subjects. The concave and convex RVA
      from T1 to T12, the RVADs and the RVARas were measured on AP digital radiographs
      of 44 female patients with right convex idiopathic scoliosis and 14 normal
      females. Patients were divided into three groups: normal subjects (group 1),
      scoliotic patients with Cobb's angle equal or <30 degrees  (group 2) and
      scoliotic patients with Cobb's angle over 30 degrees  (group 3). Overall values
      (mean +/- SD) of the RVAs on the concave side were 90.5 degrees  +/- 17 degrees 
      in group 1, 90.3 degrees  +/- 15.8 degrees  in group 2 and 88.8 degrees  +/- 15.4
      degrees  in group 3. On the convex side, values were 90.0 degrees  +/- 17.3
      degrees  in group 1, 86.3 degrees  +/- 13.7 degrees  in group 2 and 80.7 degrees 
      +/- 14.4 degrees  in group 3. Overall values (mean +/- SD) of the RVADs at all
      levels were 0.5 degrees  +/- 0.7 degrees  in group 1, 4.0 degrees  +/- 4.8
      degrees  in group 2 and 8.0 degrees  +/- 4.0 degrees  in group 3. The RVARa
      values (mean +/- SD) at all levels was 1.008 degrees  +/- 0.012 degrees  in group
      1, 1.041 degrees  +/- 0.061 degrees  in group 2 and 1.102 degrees  +/- 0.151
      degrees  in group 3. RVAD and RVARa values in the scoliotic segment were greater
      in patients with untreated scoliosis over 30 degrees  than in patients with an
      untreated deformity of <30 degrees  or normal subjects. A significant effect
      between groups was observed for the RVA, RVAD and RVARa variables. Measurement of
      RVA, RVAD and RVARa should not only be performed at and around the apex of a
      thoracic spinal deformity, but also extended to the whole thoracic spine.

PMID- 20811756
TI  - Bone mineral density, body mass index, postmenopausal period and outcomes of low
      back pain treatment in Korean postmenopausal women.
AB  - Women going through menopause experience bone loss and increased musculoskeletal
      pain, including low back pain. This study explored the relationships between bone
      mineral density (BMD) and body mass index (BMI), postmenopausal period and
      outcomes of treatment for low back pain in postmenopausal Korean women. On
      examining the medical records of 78 postmenopausal women hospitalized for low
      back pain, investigators found that women with low BMD were older and had been
      postmenopausal for longer periods than women with normal BMD. Postmenopausal
      length was positively correlated with pain scores at day 15 and 20 post-admission
      (P = 0.011 and 0.006) and negatively correlated with T-scores (P = 0.002). BMI
      was positively correlated with T-scores (r = 0.283, P = 0.022). In conclusion,
      age, postmenopausal length and BMI correlate with BMD in Korean women suffering
      from LBP. Larger studies investigating the associations between menopause, BMD,
      BMI and LBP seem desirable. Moreover, evidence-based therapeutic approaches
      should be explored for BMD and LBP management.

PMID- 20811757
TI  - Molecular genetics, imaging and treatment of oligodendroglial tumours.
AB  - The discovery of a genetic signature of chemosensitivity and prognosis in
      oligodendroglial tumours prompted a new optimism in glioma management. After more
      than a decade since the initial reports, where do we stand in the current
      management of oligodendroglial tumours? This review focuses on the latest
      molecular genetics, imaging characteristics, and recent trials of treatment
      paradigms for these tumours.

PMID- 20811758
TI  - Needle insertion in the foramen ovale.

PMID- 20811759
TI  - Human mesenchymal stem cell proliferation and osteogenic differentiation during
      long-term ex vivo cultivation is not age dependent.
AB  - Mesenchymal stem cells (MSCs) are of major clinical interest for the development
      of cell-based strategies to treat musculoskeletal diseases including critical
      size bone defects caused by trauma, degenerative disorders, or infections.
      Elderly people mainly suffer from critical-size bone defects from the rising
      incidence of trauma, osteoporosis, and arthroplasties. In this study we
      investigated the influence of donor age on proliferation and osteogenic
      differentiation in long-term ex vivo cultures of primary human MSCs from patients
      in different age groups. Fifteen patients (8 men/7 women) comprised three age
      groups: (I) <50 years, (II) 50-65 years, and (III) >65 years. MSCs harvested from
      bone marrow derived from routine surgical procedures were isolated and cultured
      in standard medium over eight passages. Osteogenic differentiation was induced by
      dexamethasone (10 nM), ascorbic acid (300 MUM), and beta-glycerophosphate (3.5
      mM). Osteogenic differentiation capacity of MSCs was quantified by alkaline
      phosphatase (ALP) activity, fluorescence-activated cell sorting (FACS) analysis
      of the surface markers CD9, CD90, CD54, CD166, CD105, CD44, and CD73, and RT-PCR
      for Coll I and II, Cbfa 1, ALP, OC, BSP1, and GAPDH genes characterized the
      phenotypic changes during monolayer expansion. In vitro chondrogenic
      differentiation was analyzed by immunohistochemistry and RT-PCR. Progenitor cells
      could be expanded in the long term from all bone marrow donations. FACS single
      staining analysis from MSCs showed no significant difference between the age
      groups. The surface antigen CD166 was predominantly found in all cell cultures
      independently of differentiation stage. Comparison of expanded and differentiated
      MSCs within a single age group showed that undifferentiated MSCs had higher CD44
      levels. Osteogenic stimulation of MSCs was confirmed by measuring ALP activity.
      The highest ALP activity was found in probands of the age group >65 years.
      Additionally, we observed a tendency toward male-specific ALP increase during
      differentiation. Osteogenic marker gene expression in MSCs was detected by RT
      PCR. No significant expression differences were detected between the three donor
      age groups. Micromass culture of MSCs resulted histologically and
      immunohistologically in a chondrogenic phenotype. Elderly osteoprogenitor cell
      donors are a highly clinically relevant patient population. In summary,
      cultivation leads to a reduced osteogenic differentiation capacity regardless of
      age. Because donor age does not affect osteogenic differentiation potential, it
      should not be used as an exclusion criterion for autologous transplantation of
      human adult MSCs.

PMID- 20811760
TI  - The association between preschool behavioural problems and internalizing
      difficulties at age 10-12 years.
AB  - The aim was to study the association between preschool behavioural problems and
      emotional symptoms in 10- to 12-year-old children. The study was based on the
      Aarhus Birth cohort, Denmark, and included 1,336 children. Based on the parent
      administered preschool behaviour questionnaire (PBQ), we identified three not
      mutually exclusive preschool behavioural categories: anxious-fearful (n = 146),
      hyperactive-distractible (n = 98), and hostile-aggressive (n = 170). Children
      without any known symptoms were considered well adjusted (n = 1,000). Borderline
      emotional (n = 105) and emotional difficulties (n = 136) were measured at age 10
      12 years with the parent-administered strength and difficulties questionnaire
      (SDQ). Multinomial logistic regression analyses were used to adjust for potential
      confounding factors. We found that anxious-fearful behaviour and hostile
      aggressive preschool behaviour were associated with twice the risk of school-age
      emotional difficulties. Comorbidity or confounding failed to explain these
      results. Hyperactive-distractible preschool behaviour was not associated with
      school-age emotional difficulties. Preschool anxious-fearful behaviour was
      associated with school-age emotional difficulties, suggesting internalizing
      symptom stability in some children from early childhood. Preschool hostile
      aggressive behaviour was also associated with school-age emotional difficulties,
      which suggests transformation of one behavioural dimension into another through
      childhood, and the need to focus on both early internalizing difficulties and
      hostile-aggressive behaviour as risk factors for later internalizing
      difficulties.

PMID- 20811761
TI  - Advantages of new materials in fascia transversalis reinforcement for inguinal
      hernia repair.
AB  - PURPOSE: We investigated whether new absorbable materials can be used in the
      treatment of inguinal hernia with the same efficacy as the traditionally used
      polypropylene. METHODS: We compared local tissue inflammation and fibrous
      reaction, postoperative complications (bleeding, wound haematoma, wound
      infection) and postoperative recovery time (time of mobilisation) in rats
      (Fischer strain) after implantation of a polypropylene mesh (PPM) (Prolene,
      Ethicon, Bracknell, UK) or a dual component fibrin mesh (DCFM) (Tachosil,
      Nycomed, Marlow, UK), between the muscle layer and the fascia transversalis
      defect. We further compared direct hernia repair methods using Lichtenstein's
      operation in humans after implantation of either PPM or DCFM for fascia
      transversalis reinforcement regarding postoperative pain and complications, time
      needed for patient mobilisation, and recurrence. RESULTS: The results show that
      implantation of DCFM in rats resulted in milder inflammatory response and thicker
      fibrous tissue formation. Patients implanted with DCFM had significantly lower
      postoperative pain scores on a visual-analogue scale and lower analgesic use. The
      overall incidence of postoperative complications was significantly reduced with
      the use of DCFM. The incidence of recurrence after 24-month follow-up was the
      same in both groups. CONCLUSION: This study has shown that DCFM has the same
      short-term efficacy in hernia treatment as the standard PPM, with a reduction in
      postoperative pain and analgesic use, and a decrease in overall postoperative
      complications. In the rat model, DCFM resulted in milder inflammatory response
      and thicker fibrous plate than the PPM. Further biomechanical testing and longer
      follow-up is necessary, but initial results are promising.

PMID- 20811762
TI  - Omental incarceration may cause hydrocele and this hydrocele confused simple or
      scrotal hydrocele.
AB  - BACKGROUND: The recommended approach to hydrocele repair in children is inguinal.
      Recently, a transscrotal approach has been recommended for hydroceles in
      children. This report describes our experience with hydrocele with omentum
      incarceration. METHODS: This retrospective study reviewed the records of ten
      children who underwent inguinal hydrocele repair with omentum incarceration in
      our clinic. RESULTS: The mean age of the patients was 4.5 years (range 1.5-16).
      Hydroceles were located on the right side in all patients. Scrotal erythema,
      inguinal pain, signs of intestinal obstruction and hernia sac were not
      determined. Hydrocele repairs were made by inguinal approach in all patients. The
      procesus vaginalis was rougher than normal and noted as the hernia sac. Thus, the
      hernia sacs were opened and omental incarceration was defined in all cases.
      Omentum protruded into the abdomen in all cases. A high ligation was performed
      and the distal parts of the sacs were fenestrated. CONCLUSIONS: In the light of
      our experience, a scrotal approach to hydrocele repair in children would be
      difficult in cases of incarceration with hernia. Omental incarceration may cause
      hydrocele, and this hydrocele can be confused with normal hydrocele. Therefore,
      we would continue to recommend an inguinal approach for childhood hydroceles.

PMID- 20811763
TI  - An unusual presentation of neurosyphilis as a probable migraine.
AB  - We describe a case which initially presented as persistent and untreatable
      probable migraine, which was subsequently diagnosed as neurosyphilis during the
      clinical evaluation. All symptoms regressed after appropriate treatment. We
      suggest that the possibility of neurosyphilis should be taken into account in the
      differential diagnosis of a persistent headache which does not respond to
      medication.

PMID- 20811764
TI  - Adiposis dolorosa of scalp presenting with severe headache: an unusual case.
AB  - A 46-year-old female, known case of adiposis dolorosa since adolescence, noticed
      painful thickening of scalp in bilateral parieto-occipital areas and vertex 1
      year back. Six weeks prior to the presentation to our service, she developed
      severe occipital headache refractory to drug treatment. She improved after
      bilateral greater occipital nerve blocks. She was subjected to bilateral greater
      occipital chemical neurolysis which has given her complete pain relief.

PMID- 20811765
TI  - Stress and use of over-the-counter analgesics: prevalence and association among
      Danish 25 to 44-year-olds from 1994 to 2005.
AB  - OBJECTIVES: To examine the prevalence of over-the-counter analgesic (OTCA) use
      and perceived stress among 25 to 44-year-old men and women from 1994 to 2005; to
      examine the association between stress and OTCA use over time, and to explore
      whether the association attenuates when controlled by stress-related symptoms.
      METHODS: Cross-sectional studies were carried out in 1994, 2000 and 2005. The
      study population included men and women from ages 25 to 44 years (n (1994) =
      1,781, n (2000) = 5,819, n (2005) = 4,831). The surveys were conducted by face-to
      face interviews and the outcome measure was OTCA use. The independent variable
      was perceived stress and pain/discomfort symptoms were included as covariates.
      RESULTS: There was a significant increase in OTCA use and often feeling stressed
      from 1994 to 2005. Although there was a significant association between stress
      and OTCA use for men in all three surveys, there was no association in 2000 when
      adjusted for symptoms. For women stress and OTCA use were not associated in 1994,
      while in 2000 and 2005 the association was significant, also after adjusting for
      symptoms. CONCLUSION: The findings indicate that there may be an increasing
      overuse of OTCA in treating stress among 25 to 44-year-old men and women.

PMID- 20811766
TI  - Characterization of signaling function and expression of HLA class I molecules in
      medulloblastoma.
AB  - Although known for the important function in the immune system, MHC class I
      molecules are increasingly ascribed an alternative role in modifying signal
      transduction. In medulloblastoma, HLA class I molecules are associated with poor
      prognosis, and can induce ERK1/2 activation upon engagement with ligands that
      bind to incompletely assembled complexes (so called open conformers). We here
      demonstrate that ERK1/2 activation in medulloblastoma can occur in the absence of
      endogenously synthesized beta2m, formally excluding involvement of closed HLA
      class conformation. In addition, several experimental observations suggest that
      heterogeneity of HLA class I expression may be a reflection of the status of
      original cells before transformation, rather than a consequence of immune-based
      selection of HLA-loss mutants. These results contribute to our understanding of
      an immune system-independent role of HLA class I in the pathology of
      medulloblastoma, and cancer in general.

PMID- 20811767
TI  - Plant Hsp100/ClpB-like proteins: poorly-analyzed cousins of yeast ClpB machine.
AB  - ClpB/Hsp100 proteins act as chaperones, mediating disaggregation of denatured
      proteins. Recent work shows that apart from cytoplasm, these proteins are
      localized to nuclei, chloroplasts, mitochondria and plasma membrane. While
      ClpB/Hsp100 genes are essentially stress-induced (mainly heat stress) in
      vegetative organs of the plant body, expression of ClpB/Hsp100 proteins is noted
      to be constitutive in plant reproductive structures like pollen grains,
      developing embryos, seeds etc. With global warming looming large on the horizon,
      ways to genetically engineer plants against high temperature stress are urgently
      needed. Yeast mutants unable to synthesize active ClpB/Hsp100 protein show a
      clear thermosensitive phenotype. ClpB/Hsp100 proteins are implicated in high
      temperature stress tolerance in plants. We herein highlight the selected
      important facets of this protein family in plants.

PMID- 20811768
TI  - Design and development of EMR supporting medical process management.
AB  - Current EMR system benefits physicians by facilitating order entry and reducing
      errors. It can improve the safety and effectiveness of medical services, but
      cannot manage the whole medical process and the quality of medical services. In
      addition to physicians, EMR should be designed for all medical professionals
      because medical services cannot be accomplished by physicians alone, but also
      requires the involvement of other medical professionals. Therefore, we applied
      PDCA, the famous quality management cycle to design a comprehensive and coherent
      EMR system which can be used throughout the entire treatment process. EMR with
      the PDCA Cycle can record every order state and every treatment procedure in
      order to monitor the whole medical process. This extends the safety from planning
      the treatment to fulfilling it. By analyzing the records, doctors and hospital
      managers can perfect the medical process and improve healthcare quality. The EMR
      we designed with the PDCA Cycle provides a record entry interface for physicians
      and a worksheet interface for nurses and other professionals. Every treatment
      procedure and every change of orders or tasks will be fed back to medical
      professionals. So information generated from the beginning to the end of
      treatment will link with each other to avoid any information islands.
      Furthermore, the EMR can display the additional information intuitively and real
      timely without increasing the burden of medical professionals' work.

PMID- 20811769
TI  - The impact of labels and behaviors on the stigmatization of adults with
      Asperger's disorder.
AB  - Currently, there is a paucity of literature on stigmatization of adults with
      Asperger's Disorder (AD). Therefore, this study examined whether young adults
      hold stigmatizing views towards individuals with AD and if that stigmatization is
      elicited by behaviors or labels. College students (N = 195) read one of six
      vignettes. A modified Social Distance Scale (Link et al. 1987) was used to assess
      stigmatization. A 2 * 3 analysis of variance revealed that the social behaviors
      commonly observed in AD significantly impacted stigmatization scores, while the
      label, "Asperger's Disorder," did not. These findings have important implications
      for future research, educating the public, providing support services, and
      treatment recommendations for individuals with AD.

PMID- 20811770
TI  - Executive function mechanisms of theory of mind.
AB  - This study examined the relationship between Executive Function (EF) and Theory
      of Mind (ToM) using the Delis-Kaplan Executive Function System (D-KEFS) and three
      tests of ToM (Reading the Mind in the Eyes test (RMET), Strange Stories test, and
      Faux Pas test). Separate regression analyses were conducted, and EF predictors
      varied by ToM test. No EF domains accounted for significant variance in RMET
      scores; only estimated IQ scores were significant predictors of RMET performance.
      Verbal fluency and deductive reasoning were significant predictors of performance
      on the Strange Stories test, while verbal fluency, problem solving, and gender
      accounted for a significant variance in the Faux Pas test. Results suggest that
      the ToM tests each utilized differing cognitive mechanisms.

PMID- 20811771
TI  - HIV, sexually transmitted infections, and sexual risk behavior among transgenders
      in Indonesia.
AB  - Behavioral surveillance was undertaken among 1,150 male-to-female transgenders
      (waria) in Java, Indonesia, 2007; samples were collected for HIV and STI testing
      (n = 748). Almost all waria had ever sold sex (median duration 10 years).
      Prevalence of HIV was 24.4%, syphilis 26.8% and rectal gonorrhea and/or chlamydia
      47.0%. Syphilis and rectal STIs were associated with HIV infection. Consistent
      condom use during receptive anal sex with clients was reported by 35.9% waria and
      was higher among those who visited an STI clinic and who knew their HIV status.
      Efforts should continue to strengthen behavior change and STI care in future HIV
      prevention programs.

PMID- 20811773
TI  - Subtelomeric microduplications in three sisters with moderate mental retardation.
AB  - Copy number changes of subtelomeric regions are a common cause of mental
      retardation, occurring in approximately 5% of mentally retarded patients. New
      molecular techniques allow the identification of subtelomeric microduplications.
      We report a Tunisian family of three sisters with moderate mental retardation,
      facial dysmorphism, cardiopathy, and bilateral clinodactyly of the third and
      fourth toes, explored by MLPA, showing the same associated microduplications, 15q
      and Xq, without a concurrent deletion.

PMID- 20811772
TI  - Stability of early identified aggressive victim status in elementary school and
      associations with later mental health problems and functional impairments.
AB  - Aggressive victims-children who are both perpetrators and victims of peer
      aggression-experience greater concurrent mental health problems and impairments
      than children who are only aggressive or only victimized. The stability of early
      identified aggressive victim status has not been evaluated due to the fact that
      most studies of aggressor/victim subgroups have focused on preadolescents and/or
      adolescents. Further, whether children who exhibit early and persistent patterns
      of aggression and victimization continue to experience greater mental health
      problems and functional impairments through the transition to adolescence is not
      known. This study followed 344 children (180 girls) previously identified as
      socially adjusted, victims, aggressors, or aggressive victims at Grade 1 (Burk et
      al. 2008) to investigate their involvement in peer bullying through Grade 5. The
      children, their mothers, and teachers reported on children's involvement in peer
      aggression and victimization at Grades 1, 3, and 5; and reported on internalizing
      symptoms, externalizing symptoms, inattention and impulsivity, as well as
      academic functioning, physical health, and service use at Grades 5, 7, and 9.
      Most children categorized as aggressive victims in Grade 1 continued to be
      significantly involved in peer bullying across elementary school. Children with
      recurrent aggressive victim status exhibited higher levels of some mental health
      problems and greater school impairments across the adolescent transition when
      compared to other longitudinal peer status groups. This study suggests screening
      for aggressive victim status at Grade 1 is potentially beneficial. Further early
      interventions may need to be carefully tailored to prevent and/or attenuate later
      psychological, academic, and physical health problems.

PMID- 20811774
TI  - The effect of social defeat on tyrosine hydroxylase phosphorylation in the rat
      brain and adrenal gland.
AB  - Tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine
      biosynthesis, is regulated acutely by protein phosphorylation and chronically by
      protein synthesis. No studies have systematically investigated the
      phosphorylation of these sites in vivo in response to stressors. We specifically
      investigated the phosphorylation of TH occurring within the first 24 h in
      response to the social defeat stress in the rat adrenal, the locus coeruleus,
      substantia nigra and ventral tegmental area. Five groups were investigated; home
      cage control (HCC), two groups that underwent social defeat (SD+) which were
      sacrificed either 10 min or 24 h after the end of the protocol and two groups
      that were put into the cage without the resident being present (SD-) which were
      sacrificed at time points identical to the SD+. We found at 10 min there were
      significant increases in serine 40 and 31 phosphorylation levels in the locus
      coeruleus in SD+ compared to HCC and increases in serine 40 phosphorylation
      levels in the substantia nigra in SD+ compared to SD-. We found at 24 h there
      were significant increases in serine 19 phosphorylation levels in the ventral
      tegmental area in SD+ compared to HCC and decreases in serine 40 phosphorylation
      levels in the adrenal in SD+ compared to SD-. These findings suggest that the
      regulation of TH phosphorylation in different catecholamine-producing cells
      varies considerably and is dependent on both the nature of the stressor and the
      time at which the response is analysed.

PMID- 20811775
TI  - Relationship between major adverse cardiac events and angiographic findings in
      dialysis patients.
AB  - BACKGROUND: In dialysis patients, coronary angiography (CA) predicts major
      adverse coronary events (MACE) better than non-invasive tests. The aim of this
      study was to investigate in such patients the relationship between coronary
      atherosclerotic damage shown by angiography and MACE, during an average follow-up
      period of more than 5 years. PATIENTS AND METHODS: Coronary angiography was
      performed in 63 dialysis patients (mean age 56 +/- 12 years, 49 men); 37 subjects
      awaiting kidney transplantation had no history of cardiac disease, whereas the
      remaining 26 patients had clinical evidence of coronary artery disease (CAD).
      During a follow-up period of 62 +/- 20 months (range 12-109), all the MACE were
      recorded. Statistical analysis was carried out by dividing the patients into two
      groups, those who had MACE (MACE group) and those who were free of cardiac events
      (FCE group). Severe CAD on CA was defined as luminal stenosis >= 75% in at least
      one vessel. Logistic regression analysis and Cox regression analysis were carried
      out in order to evaluate which variable was associated with MACE. RESULTS: At the
      end of follow-up, 17 subjects had MACE and severe CAD was shown in the epicardial
      arteries of 31 patients (49%). Compared to the FCE group, the MACE group had
      older age (65 +/- 10 vs 53 +/- 11 years, P = 0.002), lower diastolic blood
      pressure (79 +/- 7 vs 85 +/- 7 mmHg, P = 0.0037), higher prevalence of CAD (82 vs
      30%, P = 0.0002) and cerebrovascular disease (41 vs 15%, P = 0.0278). Coronary
      artery damage was higher in the MACE group than in the FCE group. Logistic and
      Cox regression analyses showed that age was the only variable independently
      associated with MACE (OR 1.109 95% CI 1.022-1.204, P = 0.0133, hazard ratio 1.066
      95% CI 1.010-1.125, P = 0.02, respectively). After removal of age from the model,
      MACE were independently associated with haemodynamic stenosis of coronary
      arteries (OR 7.429 95% CI 1.829-30.173, P = 0.005, hazard ratio 5.992 95% CI
      1.655-21.698, P = 0.006, respectively). Event-free survival was much better in
      the 37 renal transplant candidates with no history of CAD than in the 26 patients
      who had clinical evidence of CAD. CONCLUSIONS: This observational study confirms
      that in dialysis patients coronary atherosclerotic damage shown by angiography is
      strongly related to MACE and that age and severe CAD are major risk factors for
      MACE.

PMID- 20811776
TI  - Comparative symbiotic performance of native rhizobia of the Flooding Pampa and
      strains currently used for inoculating Lotus tenuis in this region.
AB  - The Flooding Pampa (FP) is the most important area for cattle breeding in
      Argentina. In this region, persistence and yield of typical forage legumes are
      strongly limited by soil salinity and alkalinity, which affect around 30% of the
      total area. Instead, naturalized Lotus tenuis is the main forage legume in this
      region. Rhizobial strains currently used for inoculating L. tenuis in the FP are
      exotic or native from non-saline soils of this region, their taxonomic identity
      being unknown. Assuming that rhizobia native from the most restrictive
      environments are well adapted to adverse conditions, the use of such isolates
      could improve the productivity of L. tenuis in the FP. Hence, the goal of this
      study was to evaluate the symbiotic efficiency of selected L. tenuis rhizobia
      native from the FP, as compared with strains currently used for field inoculation
      of this legume. Under non-stressing conditions, the symbiotic performance of
      native strains of FP exceeded those ones currently used for L. tenuis. Moreover,
      the symbiotic performance of the native strain ML103 was considerably high under
      salt stress, compared with strains currently used as inoculants. Analysis of 16S
      rRNA gene sequencing revealed that unclassified rhizobia currently used for field
      inoculation of L. tenuis and native strains grouped with the genus Mesorhizobium.
      As a whole, results obtained demonstrate that soils of the FP are a source of
      efficient and diverse rhizobia that could be used as a sustainable agronomic tool
      to formulate inoculants that improve forage yield of L. tenuis in this region.

PMID- 20811777
TI  - Emergence of self-reproduction in cooperative chemical evolution of prebiological
      molecules.
AB  - The paper presents a model of coevolution of short peptides (P) and short
      oligonucleotides (N) at an early stage of chemical evolution leading to the
      origin of life. The model describes polymerization of both P and N types of
      molecules on mineral surfaces in aqueous solution at moderate temperatures. It is
      assumed that amino acid and nucleotide monomers were available in a prebiotic
      milieu, that periodic variation in environmental conditions between dry/warm and
      wet/cool took place and that energy sources were available for the
      polymerization. An artificial chemistry approach in combination with agent-based
      modeling was used to explore chemical evolution from an initially random mixture
      of monomers. It was assumed that the oligonucleotides could serve as templates
      for self-replication and for translation of peptide compositional sequences, and
      that certain peptides could serve as weak catalysts. Important features of the
      model are the short lengths of the peptide and oligonucleotide molecules that
      prevent an error catastrophe caused by copying errors and a finite diffusion rate
      of the molecules on a mineral surface that prevents excessive development of
      parasitism. The result of the simulation was the emergence of self-replicating
      molecular systems consisting of peptide catalysts and oligonucleotide templates.
      In addition, a smaller but significant number of molecules with alternative
      compositions also survived due to imprecise reproduction and translation of
      templates providing variability for further evolution. In a more general context,
      the model describes not only peptide-oligonucleotide molecular systems, but any
      molecular system containing two types of polymer molecules: one of which serves
      as templates and the other as catalysts.The presented coevolutionary system
      suggests a possible direction towards finding the origin of molecular
      functionality in a prebiotic environment.

PMID- 20811778
TI  - Determination of antioxidant constituents in cactus pear fruits.
AB  - An analytical study was carried out on the presence of antioxidant constituents
      and the in vitro antioxidant capacity in the extracts of three species of Spanish
      red-skinned cactus pear fruits (Opuntia ficus-indica, Opuntia undulata and
      Opuntia stricta). The cactus pear fruit extracts were analyzed for determined
      constituents: ascorbic acid, flavonoids (quercetin, isorhamnetin, myricetin,
      kaempferol and luteolin), betalains, taurine, total carotenoids and total
      phenolics. The antioxidant capacity was assessed by means of two different
      methods: the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (Trolox
      equivalent antioxidant capacity) method and the 2,2-diphenyl-1-picrylhydrazyl
      radical method. Opuntia ficus-indica fruit extract had the strongest antioxidant
      capacity and taurine content. O. stricta fruits were the richest in ascorbic acid
      and total phenolics, whereas O. undulata fruits showed the highest carotenoid
      content. Quercetin and isorhamnetin were the main flavonoids detected. This study
      provides basic information on the presence of bioactive compounds and antioxidant
      capacity in extracts of cactus pear fruits, in order to consider these extracts
      as ingredient for the production of health-promoting food.

PMID- 20811779
TI  - Standardization of surgical and pathologic variables is needed in multicenter
      trials of adjuvant therapy for pancreatic cancer: results from the ACOSOG Z5031
      trial.
AB  - BACKGROUND: Standardization of surgical and pathologic techniques is crucial to
      the interpretation of studies evaluating adjuvant therapies for pancreatic cancer
      (PC). METHODS: To assess the degree to which treatment administered prior to
      enrollment of patients in trials of adjuvant therapy is quality controlled, the
      operative and pathology reports of patients in American College of Surgeons
      Oncology Group (ACOSOG) Z5031-a national trial of chemoradiation following
      pancreaticoduodenectomy (PD)-were rigorously evaluated. We analyzed variables
      with the potential to influence staging or outcome. RESULTS: 80 patients reported
      to have undergone R0 (75%) or R1 (25%) pylorus-preserving (38%) or standard (62%)
      PD were evaluated. A search for metastases was documented in 96% of cases. The
      proximity of the tumor to the superior mesenteric vein was reported in 69%; vein
      resection was required in 9% and lateral venorrhaphy in 14%. The method of
      dissection along the superior mesenteric artery (SMA) was described in 68%, being
      ultrasonic dissection (17%), stapler (24%), and clamp and cut (59%). SMA
      skeletonization was described in 25%, and absence of disease following resection
      was documented in 24%. The surgeon reported marking the critical SMA margin in
      25%; inking was documented in 65% of cases and evaluation of the SMA margin was
      reported in 47%. A range of 1-49 lymph nodes was evaluated. Only 34% of pathology
      reports met College of American Pathologists criteria. CONCLUSIONS: Trials of
      adjuvant therapy following PD suffer from a lack of standardization and quality
      control prior to patient enrollment. These data suggest areas for improvement in
      the design of multidisciplinary treatment protocols.

PMID- 20811780
TI  - Promoting health equity in cities through evidence-based action.
AB  - The impact of the urban setting on health and, in particular, health inequities
      has been widely documented. However, only a few countries have examined their
      inter- or intra-city health inequalities, and few do so regularly. Information
      that shows the gaps between cities or within the same city is a crucial
      requirement to trigger appropriate local actions to promote health equity. To
      generate relevant evidence and take appropriate actions to tackle health
      inequities, local authorities need a variety of tools. In order to facilitate a
      comprehensive understanding of health systems performance, these tools should:
      (1) adopt a multi-sectorial approach; (2) link evidence to actions; (3) be simple
      and user-friendly; and (4) be operationally feasible and sustainable. In this
      paper we have illustrated the use of one such tool, The World Health
      Organization's Urban HEART, which guides users through a process to identify
      health inequities, focusing on health determinants and then developing actions
      based on the evidence generated. In a time of increasing financial constraints,
      there is a pressing need to allocate scarce resources more efficiently. Tools are
      needed to guide policy makers in their planning process to identify best-practice
      interventions that promote health equity in their cities.

PMID- 20811781
TI  - Modeling nosocomial transmission of rotavirus in pediatric wards.
AB  - Nosocomial transmission of viral and bacterial infections is a major problem
      worldwide, affecting millions of patients (and causing hundreds of thousands of
      deaths) per year. Rotavirus infections affect most children worldwide at least
      once before age five. We present here deterministic and stochastic models for the
      transmission of rotavirus in a pediatric hospital ward and draw on published data
      to compare the efficacy of several possible control measures in reducing the
      number of infections during a 90-day outbreak, including cohorting, changes in
      healthcare worker-patient ratio, improving compliance with preventive hygiene
      measures, and vaccination. Although recently approved vaccines have potential to
      curtail most nosocomial rotavirus transmission in the future, even short-term
      improvement in preventive hygiene compliance following contact with symptomatic
      patients may significantly limit transmission as well, and remains an important
      control measure, especially where resources are limited.

PMID- 20811782
TI  - Inhibition of insulin and T3-induced fatty acid synthase by hexanoate.
AB  - Fatty acid synthase (FAS) is responsible for the de novo synthesis of palmitate
      and stearate. This enzyme is activated by insulin and T(3), and inhibited by
      fatty acids. In this study, we show that insulin and T(3) have an inducing effect
      on FAS enzymatic activity, which is synergetic when both hormones are present.
      Octanoate and hexanoate specifically inhibit this hormonal effect. A similar
      inhibitory effect is observed at the level of protein expression. Transient
      transfections in HepG2 cells revealed that hexanoate inhibits, at least in part,
      FAS at a transcriptional level targeting the T(3) response element (TRE) on the
      FAS promoter. The effect of C6 on FAS expression cannot be attributed to a
      modification of insulin receptor activation or to a decrease in T(3) entry in the
      cells. Using bromo-hexanoate, we determined that hexanoate needs to undergo a
      transformation in order to have an effect. When incubating cells with
      triglyceride-hexanoate or carnitine-hexanoate, no effect on the enzymatic
      activity induced by insulin and T(3) is observed. A similar result was obtained
      when cells were incubated with betulinic acid, an inhibitor of the diacylglycerol
      acyltransferase. However, the incubation of cells with Triacsin C, a general
      inhibitor of acyl-CoA synthetases, completely reversed the inhibitory effect of
      hexanoate. Our results suggest that in hepatic cells, hexanoate needs to be
      activated into a CoA derivative in order to inhibit the insulin and T(3)-induced
      FAS expression. This effect is partially transcriptional, targeting the TRE on
      the FAS promoter.

PMID- 20811783
TI  - The import of trust in regular providers to trust in cancer physicians among
      white, African American, and Hispanic breast cancer patients.
AB  - BACKGROUND: Interpersonal trust is an important component of the patient-doctor
      relationship. Little is known about patients' trust in the multiple providers
      seen when confronting serious illness. OBJECTIVES: To characterize breast cancer
      patients' trust in their regular providers, diagnosing physicians, and cancer
      treatment team and examine whether high trust in one's regular provider confers
      high trust to cancer physicians. DESIGN: In-person interviews. PARTICIPANTS: 704
      white, black, and Hispanic breast cancer patients, age 30 to 79, with a first
      primary in situ or invasive breast cancer who reported having a regular provider.
      MEASURES: We measure trust in: (1) regular provider, (2) diagnosing doctors, and
      (3) cancer treatment team. Other variables include demographic variables,
      preventive health care, comorbidities, time with regular provider, time since
      diagnosis, cancer stage, and treatment modality. RESULTS: Sixty-five percent of
      patients reported high trust in their regular provider, 84% indicated high trust
      in their diagnosing doctors, and 83% reported high trust in their treatment team.
      Women who reported high trust in their regular provider were significantly more
      likely to be very trusting of diagnosing doctors (OR: 3.44, 95% CI: 2.27-5.21)
      and cancer treatment team (OR: 3.09, 95% CI: 2.02-4.72 ). Black women were
      significantly less likely to be very trusting of their regular doctor (OR: 0.58,
      95% CI: 0.38-0.88) and cancer treatment team (OR: 0.45, 95% CI: 0.25-0.80).
      English-speaking Hispanic women were significantly less trusting of their
      diagnosing doctors (OR: 0.29, 95% CI: 0.11-0.80). CONCLUSIONS: Our results
      suggest that patients are very trusting of their breast cancer providers. This is
      an important finding given that research with other populations has shown an
      association between trust and patient satisfaction and treatment adherence. Our
      findings also suggest that a trusting relationship with a regular provider
      facilitates trusting relationships with specialists. Additional work is needed to
      increase interpersonal trust among black women.

PMID- 20811784
TI  - Best practices in communicating best practices: Commentary on: 'Developing and
      communicating responsible data management policies to trainees and colleagues'.
AB  - We send messages as much in how we communicate as by what we communicate.
      Learning best practices, such as those for data management proposed in the
      accompanying article, are components of becoming a responsible and contributing
      member of the community of scholars. Not only must we teach the principles
      underlying best practices, we should model and teach approaches for implementing
      those practices and help students come to view them within the larger context of
      becoming members of a professional community. How to collaborate across
      differences and how to have disputes professionally are skills all professionals
      need, and they should be taught along with the content itself.

PMID- 20811785
TI  - Ethanol and its metabolites induce histone lysine 9 acetylation and an alteration
      of the expression of heart development-related genes in cardiac progenitor cells.
AB  - Alcohol exposure during pregnancy may cause congenital heart disease (CHD), but
      the underlying mechanisms are not clear. Recent evidence suggests that ethanol
      and its metabolites can selectively increase histone H3 acetylation at lysine 9
      (H3AcK9) residue in rat hepatocytes. This may be a mechanism by which ethanol
      alters gene expression. The goal of current study is to investigate the effect of
      ethanol and its metabolites on H3AcK9 acetylation and the mRNA expression of
      heart development-related genes (GATA4, Mef2c, and Tbx5) in cardiac progenitor
      cells. We used mitochondrial activity (MTT) assay to assess the viability of
      cardiac progenitor cells. Western blotting and real-time PCR were employed to
      determine H3AcK9 acetylation and gene expression. Low levels of ethanol (50 mM),
      acetaldehyde (4 mM), and acetate (4 mM) had no effect on cell proliferation.
      However, high concentrations of ethanol (200 mM), acetaldehyde (12 mM), and
      acetate (16 mM) reduced cell viability by 30%, respectively (P < 0.05). Low
      levels of ethanol and acetate increased the acetylation of H3 lysine 9 by 2.4-
      and 2.2-fold, respectively (P < 0.05), but did not significantly change the
      expression of the heart development-related genes. High concentrations of ethanol
      and acetate increased H3 lysine 9 acetylation by 5.3- and 5.6-fold, respectively
      (P < 0.05). Moreover, high levels of ethanol and acetate significantly augmented
      the expression of GATA4 and Mef2c. Conversely, acetaldehyde (4 or 12 mM) had
      little effect on H3 lysine 9 acetylation or the expression of the heart
      development-related genes. Our studies demonstrate that high levels of ethanol or
      its metabolites induce H3AcK9 acetylation and impair cardiac progenitor cells.
      The altered histone H3 acetylation at lysine 9 has an important impact on the
      expression of the heart development-related genes, which may be one of the
      mechanisms underlying the alcohol-induced CHD.

PMID- 20811786
TI  - The persistent challenge of lupus nephritis.
AB  - Systemic lupus erythematosus has long been considered the prototypic autoimmune
      disease. Although the etiology remains enigmatic, there has been vigorous
      definition of the clinical features and the natural history. In this issue, we
      review the persistent challenge of lupus nephritis and, in particular, features
      of diagnosis as well as treatment options. It is clear that major therapeutic
      advances have occurred but there is still a considerable unmet need in the
      population. This issue does not review all the clinical problems of lupus
      nephritis, but rather attempts to place the most recent data in perspective for
      the clinician.

PMID- 20811787
TI  - The association of protein S Tokushima-K196E with a risk of deep vein thrombosis.
AB  - Deep vein thrombosis (DVT) is a multifactorial disease caused by acquired risk
      factors such as a bed rest, surgery and malignancies. Although the factor V
      Leiden and the prothrombin-20210G>A mutation do not exist in Japanese
      populations, a mutation in protein S (PS) Tokushima (K196E) has been attracting
      attention in Japan. In this study, the genetic contribution of PS Tokushima
      (K196E) was evaluated in 60 Japanese patients with thrombosis in comparison to
      234 healthy volunteers and 88 patients without thrombosis. Genes associated with
      the response to warfarin, cytochrome P450 2C9 (CYP2C9), vitamin K epoxide
      reductase complex subunit 1 (VKORC1), and gamma-glutamyl carboxylase (GGCX) were
      also investigated simultaneously. PS Tokushima (K196E) was detected in 6 patients
      with thrombosis, in 3 without thrombosis and in 3 healthy volunteers, indicating
      that there is a high frequency of the PS Tokushima (K196E). There were no
      significant differences of CYP2C9, VKORC1 or GGCX between the patients with and
      without DVT. Therefore, PS Tokushima (K196E) is an important genetic risk factor
      for DVT in the Japanese population.

PMID- 20811788
TI  - Determinants of pain in patients with carpal tunnel syndrome.
AB  - BACKGROUND: Carpal tunnel syndrome causes numbness, weakness, and atrophy. Pain
      without numbness is not characteristic of this disease. QUESTIONS/PURPOSES: We
      tested the hypothesis that among patients with carpal tunnel syndrome confirmed
      by electrophysiologic testing, pain catastrophizing and/or depression would be
      good predictors of pain intensity at the time of diagnosis, whereas nerve
      conduction velocity would not. PATIENTS AND METHODS: Fifty-four patients
      completed a measure of tendency to misinterpret pain, a measure of depressive
      symptoms, anxiety about pain, self-efficacy in response to pain, and a five-point
      Likert measure of pain intensity. One-tailed Spearman correlation was performed
      to find a correlation between pain and continuous variables. One-way ANOVA was
      performed to assess differences between categorical variables. For each group,
      all variables with significant correlations with pain intensity were included in
      a multiple linear regression analysis. RESULTS: Sex, age, and electrophysiologic
      measures did not correlate with pain intensity. All measures of illness behavior
      correlated with pain intensity and were entered in a multiple linear regression
      model; only misinterpretation of nociception and depression were significantly
      associated and accounted for 39% of the variation in pain intensity. CONCLUSIONS:
      Illness behavior (specifically depression and misinterpretation of nociception)
      predicts pain intensity in patients with carpal tunnel syndrome.

PMID- 20811790
TI  - Letter to the editor: Posterior malleolar stabilization of syndesmotic injuries
      is equivalent to screw fixation.

PMID- 20811791
TI  - Right ventricular failure--a continuing problem in patients with left ventricular
      assist device support.
AB  - The discrepancy between the limited availability of donor hearts and the ever
      increasing number of patients with heart failure has led to the increasing use of
      left ventricular assist devices (LVAD) as a bridge to transplant. One of the main
      complications inherent following institution of LVAD therapy is right ventricular
      (RV) failure, manifested by the need for inotropic and/or nitric oxide support
      >14 days after LVAD implant and/or the need for right-sided mechanical
      circulatory support. RV failure is a major contributor of significant morbidity
      and mortality after LVAD placement. The complex pathophysiology of RV failure,
      which could potentially be related to RV myocardial dysfunction, interventricular
      dependence, and RV afterload, has led to inconsistencies in predicting risk
      factors for RV dysfunction. Several strategies have evolved over the years of
      experience with mechanical circulatory support that have aimed to avoid as well
      as reduce the incidence of RV failure. It is imperative that patients who
      definitely need biventricular support are identified. Despite the numerous risk
      factors identified in many studies as well as the development of risk factor
      profile scores, this continues to be a challenging problem. However, the lower
      incidence of RV failure following LVAD in the current era is encouraging,
      suggesting a favorable relationship between RV unloading and function, and
      continuous-flow physiology.

PMID- 20811796
TI  - Calcium and Magnesium Supplementation Improves Serum OPG/RANKL in Calcium
      Deficient Ovariectomized Rats.
AB  - Magnesium (Mg) deficiency has been reported to result in increases in bone
      resorption through changes in the cytokine system, such as decreases in serum
      osteoprotegerin (OPG) concentrations and increases in receptor activator of NF
      kappaB ligand (RANKL) concentrations. However, there are few data about the
      effects of Mg supplementation on OPG and RANKL. This study was carried out to
      investigate the effects of Mg supplementation on bone mineral density (BMD), bone
      mineral content (BMC), serum OPG, and RANKL in ovariectomized (OVX) rats relative
      to calcium (Ca) intake levels. Fifty-five Sprague-Dawley female rats were divided
      into the following five groups and fed for 12 weeks as indicated: sham-operated
      control group (sham), OVX Ca-deficient group (OLCa, 0.1% Ca and 0.05% Mg), OVX Ca
      deficient and Mg-supplemented group (OLCaMg, 0.1% Ca and 0.1% Mg), OVX Ca
      adequate group (OACa, 0.5% Ca and 0.05% Mg), and OVX Ca-adequate and Mg
      supplemented group (OACaMg, 0.5% Ca and 0.1% Mg). The BMD of the lumbar spine,
      femur, and tibia in the OVX groups was significantly lower than that in the sham
      group. The OVX group with an adequate-Ca diet showed significantly higher BMC of
      the lumbar spine compared to the low Ca-diet group regardless of Mg
      supplementation. The OACaMg group had significantly higher levels of OPG and
      OPG/RANKL ratio than did the OLCa group. From the above results, it is still
      unclear whether Mg supplementation can improve bone mineral status, while Mg
      supplementation with an adequate-Ca diet resulted in a change in cytokines that
      may promote bone formation.

PMID- 20811795
TI  - Prolapse surgery in women of 80 years and older using the ProliftTM technique.
AB  - INTRODUCTION AND HYPOTHESIS: Treatment of genital prolapse in very elderly women
      is challenging. Although pessary therapy and colpocleisis are effective, they
      also have drawbacks. There is only scarce literature about surgical therapy in
      this age cohort, particularly regarding the use of meshes. METHODS: We aimed to
      evaluate the feasibility, intraoperative complications, and short-term follow-up
      results of the ProliftTM technique in 62 women aged over 80 years. Mean follow-up
      time was 6.2 months. RESULTS: ProliftTM implantation was well tolerated by
      patients with regard to surgery and anesthesia, and hospitalization was
      relatively short (mean, 3.9 days). Intraoperative complications occurred in 1.6%.
      Early postoperative complications included increased post-void residual volume
      (25.8%), urinary tract infection (3.2%), and moderate or severe pain (17.7%).
      Five patients (8.3%) developed prolapse recurrence, and mesh retraction was
      observed in six patients (10%). There was no mesh erosion at short-term follow
      up. CONCLUSIONS: Treatment of advanced prolapse using ProliftTM in very elderly
      women is a feasible, safe, and effective surgical option, preserving a functional
      vagina. Thus, this may represent one alternative to colpocleisis.

PMID- 20811797
TI  - Covalent immobilization of beta-1,4-glucosidase from Agaricus arvensis onto
      functionalized silicon oxide nanoparticles.
AB  - An efficient beta-1,4-glucosidase (BGL) secreting strain, Agaricus arvensis, was
      isolated and identified. The relative molecular weight of the purified A.
      arvensis BGL was 98 kDa, as determined by sodium dodecylsulfate polyacrylamide
      gel electrophoresis, or 780 kDa by size exclusion chromatography, indicating that
      the enzyme is an octamer. Using a crude enzyme preparation, A. arvensis BGL was
      covalently immobilized onto functionalized silicon oxide nanoparticles with an
      immobilization efficiency of 158%. The apparent V (max) (k (cat)) values of free
      and immobilized BGL under standard assay conditions were 3,028 U mg protein(-1)
      (4,945 s(-1)) and 3,347 U mg protein(-1) (5,466 s(-1)), respectively. The
      immobilized BGL showed a higher optimum temperature and improved thermostability
      as compared to the free enzyme. The half-life at 65  degrees C showed a 288-fold
      improvement over the free BGL. After 25 cycles, the immobilized enzyme still
      retained 95% of the original activity, thus demonstrating its prospects for
      commercial applications. High specific activity, high immobilization efficiency,
      improved stability, and reusability of A. arvensis BGL make this enzyme of
      potential interest in a number of industrial applications.

PMID- 20811798
TI  - Anatomic study of the axillary nerve in a Chinese cadaveric population:
      correlation of the course of the nerve with proximal humeral fixation with
      intramedullary nail or external skeletal fixation.
AB  - INTRODUCTION: The axillary nerve can be injured during external skeletal fixation
      with Schanz screws or proximal locking screws of intramedullary nails. Being
      aware of the axillary nerve's anatomic relationship to the proximal humerus is
      vital for avoiding complications. METHODS: We investigated the relationship of
      the axillary nerve to surrounding bony landmarks by studying 88 axillary nerves
      in 44 embalmed cadaveric adult Chinese males. These measurements were then
      compared with the results from a similar study among Caucasians using the same
      reference points. RESULTS: We identified three significantly different parameters
      between our Chinese and the previously studied Caucasian subjects (P <= 0.05):
      the distances from the superior aspect of the humeral head to the axillary nerve
      (D1) (5.2 +/- 0.7 vs. 6.09 +/- 0.65 cm, respectively); surgical neck to axillary
      nerve (D2) (2.0 +/- 0.7 vs. 1.72 +/- 0.84 cm); and humeral length (D3) (29.0 +/-
      2.2 vs. 35.25 +/- 5.7 cm). The D1 distance ranged from 4.0 to 6.7 cm; the D2
      distance ranged from 1.0 to 4.1 cm; and the entire humeral length (D3) ranged
      from 23.3 to 33.3 cm. Iatrogenic injury to the axillary nerve could be reduced by
      placing pins and screws in proper directions using portable C-arm fluoroscopic
      guidance, drill-guided protective systems, and a mini-open-incision with muscle
      spreading and drill protective systems directly placed on the bone. CONCLUSION:
      Because of physical variability among individual patients and populations,
      surgeons should consider the possible courses of the axillary nerve when treating
      proximal humeral fractures.

PMID- 20811799
TI  - Interferon-gamma-inducible kynurenines/pteridines inflammation cascade:
      implications for aging and aging-associated psychiatric and medical disorders.
AB  - This review of literature and our data suggests that up-regulated production of
      interferon-gamma (IFNG) in periphery and brain triggers a merger of tryptophan
      (TRY)-kynurenine (KYN) and guanine-tetrahydrobiopterin (BH4) metabolic pathways
      into inflammation cascade involved in aging and aging-associated medical and
      psychiatric disorders (AAMPD) (metabolic syndrome, depression, vascular cognitive
      impairment). IFNG-inducible KYN/pteridines inflammation cascade is characterized
      by up-regulation of nitric oxide synthase (NOS) activity (induced by KYN) and
      decreased formation of NOS cofactor, BH4, that results in uncoupling of NOS that
      shifting arginine from NO to superoxide anion production. Superoxide anion and
      free radicals among KYN derivatives trigger phospholipase A2-arachidonic acid
      cascade associated with AAMPD. IFNG-induced up-regulation of indoleamine 2,3
      dioxygenase (IDO), rate-limiting enzyme of TRY-KYN pathway, decreases TRY
      conversion into serotonin (substrate of antidepressant effect) and increases
      production of KYN associated with diabetes [xanthurenic acid (XA)], anxiety
      (KYN), psychoses and cognitive impairment (kynurenic acid). IFNG-inducible
      KYN/pteridines inflammation cascade is impacted by IFNG (+874) T/A genotypes,
      encoding cytokine production. In addition to literature data on KYN/TRY ratio
      (IDO activity index), we observe neopterin levels (index of activity of rate
      limiting enzyme of guanine-BH4 pathway) to be higher in carriers of high (T) than
      of low (A) producers alleles; and to correlate with AAMPD markers (e.g., insulin
      resistance, body mass index, mortality risk), and with IFN-alpha-induced
      depression in hepatitis C patients. IFNG-inducible cascade is influenced by
      environmental factors (e.g., vitamin B6 deficiency increases XA formation) and by
      pharmacological agents; and might offer new approaches for anti-aging and anti
      AAMPD interventions.

PMID- 20811800
TI  - PROlocalizer: integrated web service for protein subcellular localization
      prediction.
AB  - Subcellular localization is an important protein property, which is related to
      function, interactions and other features. As experimental determination of the
      localization can be tedious, especially for large numbers of proteins, a number
      of prediction tools have been developed. We developed the PROlocalizer service
      that integrates 11 individual methods to predict altogether 12 localizations for
      animal proteins. The method allows the submission of a number of proteins and
      mutations and generates a detailed informative document of the prediction and
      obtained results. PROlocalizer is available at http://bioinf.uta.fi/PROlocalizer/
      .

PMID- 20811801
TI  - A MP2 and DFT study of the aromatic character of polyphosphaphospholes. Is the
      pyramidality the only factor to take into consideration?
AB  - A comprehensive MP2/6-311 + G(d,p) and B3LYP/6-311 + G(d,p) study of the aromatic
      character of phospholes, P(n)(CH)(4-n )PH with n = 0-4 was conducted. For this
      purpose, the structures for these compounds were optimized at both theoretical
      levels and different magnetic properties (magnetic susceptibility anisotropy,
      chi(anis), and the nucleus-independent chemical shifts, NICS) were evaluated. For
      comparison, these magnetic properties were also calculated in the optimized
      structures with planarity constraints. We have also applied the ACID (anisotropy
      of the current-induced density) method in this analysis. The main conclusions are
      the aromatic character of these compounds, the relationship between aromaticity
      and planarity and the importance of other factors in this aromaticity.

PMID- 20811802
TI  - Effect of aeration strategy on the metabolic flux of Klebsiella pneumoniae
      producing 1,3-propanediol in continuous cultures at different glycerol
      concentrations.
AB  - The microbial production of 1,3-propaneidol (1,3-PD) by Klebsiella pneumoniae in
      continuous fermentation was investigated under low, medium and high glycerol
      concentrations in the absence and presence of oxygen. The production of 1,3-PD
      increased with increasing glycerol concentrations, reaching a maximum (266 mmol l
      1) under high glycerol concentration (760 mmol l-1) with air sparging at 0.04
      vvm. The yield of 1,3-PD, however, decreased gradually with increasing glycerol
      concentrations, with the highest yield (0.52 mol mol-1) obtained for low glycerol
      concentration (270 mmol l-1) under anaerobic condition. Enzyme activity assays
      showed that the specific activity of glycerol dehydratase was highest (0.04 U mg
      1) for culture sparged with 0.04 vvm air under high glycerol concentration. The
      specific activities of glycerol dehydrogenase and 1,3-propanediol oxidoreductase
      were also improved for all glycerol concentrations and in the presence of oxygen,
      implying that the dha operon was not repressed under microaerobic conditions.
      Analysis of metabolic fluxes showed that more carbon flux was shifted to the
      oxidative pathway with increasing glycerol concentrations, resulting in a reduced
      flux to 1,3-PD formation. However, the increases in carbon fluxes were not evenly
      distributed among the oxidative branches of the pathway. Furthermore, ethanol and
      acetic acid levels were slightly increased whereas 2,3-butanediol and lactic
      levels were greatly enhanced.

PMID- 20811803
TI  - Productivity and selective accumulation of carotenoids of the novel extremophile
      microalga Chlamydomonas acidophila grown with different carbon sources in batch
      systems.
AB  - Cultivation of extremophile microorganisms has attracted interest due to their
      ability to accumulate high-value compounds. Chlamydomonas acidophila is an
      acidophile green microalga isolated by our group from Tinto River, an acidic
      river that flows down from the mining area in Huelva, Spain. This microalga
      accumulates high concentrations of lutein, a very well-known natural antioxidant.
      The aim of this study is to assess use of different carbon sources (CO(2),
      glucose, glycerol, starch, urea, and glycine) for efficient growth of and
      carotenoid production by C. acidophila. Our results reveal that growth of the
      microalga on different carbon sources resulted in different algal biomass
      productivities, urea being as efficient as CO(2) when used as sole carbon source
      (~20 g dry biomass m(-2) day(-1)). Mixotrophic growth on glucose was also
      efficient in terms of biomass production (~14 g dry biomass m(-2) day(-1)). In
      terms of carotenoid accumulation, mixotrophic growth on urea resulted in even
      higher productivity of carotenoids (mainly lutein, probably via alpha-carotene)
      than obtained with photoautotrophic cultures (70% versus 65% relative abundance
      of lutein, respectively). The accumulated lutein concentrations of C. acidophila
      reported in this work (about 10 g/kg dry weight, produced in batch systems) are
      among the highest reported for a microalga. Glycerol and glycine seem to enhance
      beta-carotene biosynthesis, and when glycine is used as carbon source, zeaxanthin
      becomes the most accumulated carotenoid in the microalga. Strategies for
      production of lutein and zeaxanthin are suggested based on the obtained results.

PMID- 20811804
TI  - The synergism of natural compounds in the pursuit of safe and healthier food.
AB  - Food producers apply modern processing techniques and use a variety of
      preservative additives to guarantee safe food and a longer shelflife. Regrettably
      many of these impact the sensory characteristics of the foodstuffs, such as
      colour, texture, and flavour, which can result in low consumer acceptance.
      Additionally, strategies used to reduce growth of spoilage and pathogenic
      bacteria are not selective enough and may inactivate also desired microbiota.
      Food is usually overdosed with antimicrobials that are supplemented 'just in
      case.' Consequently, food producers are searching for natural preservation
      methods that are not harmful to humans. Nature offers a wide spectrum of
      biologically active (phyto) chemicals that can be used as potential natural
      preservatives. Compounds with bacterial growth-limiting properties are detected
      in all parts of plants, including their leaves, flowers, fruits, roots, etc.
      These are mostly acids, alcohols, medium and long-chain organic acids, terpenic
      compounds, and their derivatives. This study focused on the effectiveness of
      plant extracts, i.e., synergism between terpenoids and medium chain fatty acids
      in cured cooked meat. Bacterial strains that were tested include typical members
      of the spoilage microflora in vacuum (Lactobacillus curvatus) and MA-packed meats
      (Brochothrix thermosphacta). These were isolated and identified in a separate
      study. L. curvatus was observed to be very resistant against either terpenoids or
      fatty acids when used separately, whereas its growth was strongly inhibited when
      both chemicals were combined. Growth of B. thermosphacta was significantly
      inhibited when antimicrobial compounds were solely applied, whereas a blend of
      terpenoids and fatty acids showed an almost bactericidal effect.

PMID- 20811806
TI  - The utility of embryo banking in order to increase the number of embryos
      available for preimplantation genetic screening in advanced maternal age
      patients.
AB  - PURPOSE: to determine if embryo banking with PGS is more optimal than proceeding
      with PGS regardless of embryo number. METHODS: patients were divided into 2
      groups, group 1 were those that banked embryos and proceeded through another
      round of IVF prior to PGS, and group 2 underwent PGS regardless of embryo number.
      Group 2 was divided into group 2A (patients with >10 embryos) and group 2B
      (patients who had <10 embryos). RESULTS: there was no difference in embryos
      biopsied, normal embryos, number transferred, and pregnancy rate between group 1
      and 2. A significant number of patients did not have a transfer in group 2B
      (6/11) compared to group 1 (3/19) (P = 0.0419). There was no significance between
      pregnancy rates per transfer between group 1 (6/16) and group 2B (2/5).
      CONCLUSION: our data suggests that banking will increase the odds of going to
      transfer but there was no increase in pregnancy rates.

PMID- 20811807
TI  - Evaluating the power of surface attendance counts to detect long-term trends in
      populations of crevice-nesting auklets.
AB  - Power analyses are essential when developing a long-term monitoring program for a
      target species whose observation is logistically challenging and expensive. These
      analyses can be complicated when the observations have a complex variance
      structure reflecting many factors. Crevice-nesting seabirds such as least and
      crested auklets Aethia pusilla and Aethia cristatella illustrate both this need
      and these challenges. They are ecosystem indicators for the Bering Sea, a system
      expected to undergo large changes. Unfortunately, they are difficult to monitor
      as colonies occur on remote, hard to access islands in the Aleutians and Bering
      Sea, and nests occur in crevices underground, preventing direct observation.
      Current monitoring consists of breeding-season counts of auklets standing on the
      surface of sample plots in the colony; logically, a substantial decline in
      nesting population guarantees an eventual substantial decline in surface
      attendants. Yet, it remains debatable whether these highly variable counts can be
      used to statistically detect biologically relevant declines in the attending
      population let alone the nesting population. Subsequently, existing monitoring
      programs vary widely in survey design, effort levels, and daily summary
      statistics. The power of different survey designs was assessed by simulating
      observations from a state model developed from 11 years of observations using
      mixed-effects models and zero-inflated Poisson-lognormal regression. The analyses
      illustrate the process required for any monitoring program whose observations are
      described inadequately by standard statistical models. State model development
      revealed survey design refinements that reduce sampling variation. For least
      auklets, current sampling efforts provided 90% power to detect annual declines of
      11% ("Critically Endangered" using IUCN Red List criteria), 4.5% ("Endangered"),
      or 2.4% ("Vulnerable") in two, four, or six generations, respectively; crested
      auklets took a few years longer. Power was more sensitive to number of days than
      number of plots. Results appear robust across a range of bird densities,
      providing guidance for monitoring other colonies or crevice-nesting species with
      similar life history strategies. Research should now focus on illuminating the
      relationship between the attending and nesting populations. Given the frequency
      of complicated variance structures and zero counts in ecological data, the
      general statistical models used here should prove widely applicable.

PMID- 20811805
TI  - Extracellular matrix composition reveals complex and dynamic stromal-epithelial
      interactions in the mammary gland.
AB  - The mammary gland is an excellent model system to study the interplay between
      stroma and epithelial cells because of the gland's unique postnatal development
      and its distinct functional states. This review focuses on the contribution of
      the extracellular matrix (ECM) to stromal-epithelial interactions in the mammary
      gland. We describe how ECM physical properties, protein composition, and
      proteolytic state impact mammary gland architecture as well as provide
      instructive cues that influence the function of mammary epithelial cells during
      pubertal gland development and throughout adulthood. Further, based on recent
      proteomic analyses of mammary ECM, we describe known mammary ECM proteins and
      their potential functions, as well as describe several ECM proteins not
      previously recognized in this organ. ECM proteins are discussed in the context of
      the morphologically-distinct stromal subcompartments: the basal lamina, the intra
      and interlobular stroma, and the fibrous connective tissue. Future studies aimed
      at in-depth qualitative and quantitative characterization of mammary ECM within
      these various subcompartments is required to better elucidate the function of ECM
      in normal as well as in pathological breast tissue.

PMID- 20811808
TI  - Last days in the old radiation laboratory (ORL), Berkeley, California, 1954.
AB  - Govindjee, the founding editor of the Historical Corner of Photosynthesis
      Research, invited me 3 years ago to tell the story of why I left Melvin Calvin's
      laboratory in the mid 1950s long before the 1961 Nobel Prize in Chemistry was
      awarded to Calvin for the path of carbon in photosynthesis. I have already
      written my scientific perspective on this topic (see Benson (Photosynth Res 73:29
      49, 2002); also see Bassham (Photosynth Res 76:35-52, 2003) as he was also a
      major player in this research). Here, I present my recollections of my last days
      in the old radiation laboratory (ORL) at Berkeley, California. References have
      been added by Govindjee for the benefit of the readers.

PMID- 20811809
TI  - Celebrating Andrew Alm Benson's 93rd birthday.
AB  - We celebrate Andy Benson's 93rd birthday on September 24, 2010 through this
      Editorial. This short account about Andy Benson should serve as a prelude to the
      short article that Andy has written for the entire photosynthesis community,
      which gives a glimpse of why he left the field of the "path of carbon in
      photosynthesis," when he had already discovered, together with Melvin Calvin,
      James Alan Bassham, and others, most of the major steps in what we now call the
      Calvin-Benson cycle.

PMID- 20811810
TI  - Molecular cloning, expression and characterization of bovine UQCC and its
      association with body measurement traits.
AB  - Ubiquinol-cytochrome c reductase complex chaperone (UQCC) involved in the
      development and maintenance of bone and cartilage is an important candidate gene
      for body measurement traits selection through marker-assisted selection (MAS).
      The expression of UQCC is upregulated in many human and animal models of height
      as well as other stature indexes. We have cloned the cDNA sequence coding UQCC
      gene in bovine. Genomic structural analysis indicated that bovine UQCC shares a
      high similarity with human UQCC. Furthermore, Real-Time PCR analysis show that
      the expression of bovine UQCC is remarkably different in diverse tissues,
      including high level expression in the spleen, heart and windpipe, and relatively
      low expression in other tissues. We also analyzed allele frequencies in different
      cattle breeds and an association study on the selected SNPs. SNP DraI A2691T in
      intron 1 and SNP Bsh1236I A3150G in intron 8 are significantly associated with
      Body Length (BL), Rump Length (RL), Chest Depth (CD) and Pin Bone Width (PBW).
      For the A2691T SNP marker, there are significant effects on the RL (p = 0.0001),
      CD (p = 0.0059) and PBW (p < 0.0001) in 679 individuals; with A3150G SNP marker,
      there are significant effects on the BL (p = 0.0047) and CD (p = 0.0454.
      Regarding association analysis of combination of the two SNPs, there are
      significant effects on the BL (p = 0.0215), CD (p = 0.0282) and PBW (p = 0.0329)
      in the total population. The results suggest that the UQCC gene is a candidate
      gene of body measurement traits in bovine reproduction and breeding, and provide
      data for establishing of an animal model using cattle to study big animal body
      type.

PMID- 20811811
TI  - Root hair-specific EXPANSIN B genes have been selected for Graminaceae root
      hairs.
AB  - Cell differentiation ultimately relies on the regulation of cell type-specific
      genes. For a root hair cell to undergo morphogenesis, diverse cellular processes
      including cell-wall loosening must occur in a root hair cell-specific manner.
      Previously, we identified and characterized root hairspecific cis-elements (RHE)
      from the genes encoding the cell wall-loosening protein EXPANSIN A (EXPA) which
      functions preferentially on dicot cell walls. This study reports two root hair
      specific grass EXPB genes that contain RHEs. These genes are thought to encode
      proteins that function more efficiently on grass cell walls. The proximal
      promoter regions of two orthologous EXPB genes from rice (Oryza sativa; OsEXPB5)
      and barley (Hordeum vulgare; HvEXPB1) included RHE motifs. These promoters could
      direct root hair-specific expression of green fluorescent protein (GFP) in the
      roots of rice and Arabidopsis (Arabidopsis thaliana). Promoter deletion analyses
      demonstrated that the RHE motifs are necessary for root hairspecific expression
      of these EXPB promoters. Phylogenetic analysis of EXP protein sequences indicated
      that grass EXPBs are the only orthologs to these root hair-specific EXPBs,
      separating dicot EXPBs to distal branches of the tree. These results suggest that
      RHE-containing root hair-specific EXPB genes have evolved for grass-specific cell
      wall modification during root hair morphogenesis.

PMID- 20811812
TI  - The RstB sensor acts on the PhoQ sensor to control expression of PhoP-regulated
      genes.
AB  - The PhoP response regulator and PhoQ sensor, which are encoded by the phoPQ
      operon, constitute the PhoP/PhoQ two-component system. Genome-wide transcription
      analysis revealed that heterologous expression of the RstB protein, a sensor of
      the RstA/RstB two-component system, leads to enhanced transcription of PhoP
      activated genes in wild-type Salmonella. We determined that RstB-induction
      increases the levels of phoP mRNA as well as PhoP protein, while lack of the
      phoPQ genes abolishes RstB-promoted transcription of the PhoP-regulated genes.
      This regulatory function of RstB did not require its enzymatic activities, and
      thus the truncated RstB protein containing only periplasmic and transmembrane
      regions was able to promote PhoP-activated transcription. The RstB protein
      appeared to target the PhoQ sensor rather than the PhoP response regulator
      because RstB-induction failed to enhance transcription of the PhoP-regulated
      genes in a strain maintaining the normal PhoP function, even without PhoQ.

PMID- 20811813
TI  - Leukocyte common antigen-related (LAR) tyrosine phosphatase positively regulates
      osteoblast differentiation by modulating extracellular signal-regulated kinase
      (ERK) activation.
AB  - Protein tyrosine phosphatases (PTPs) are pivotal regulators of key cellular
      functions, including cell growth, differentiation, and adhesion. Previously, we
      reported that leukocyte common antigen-related (LAR) tyrosine phosphatase
      promotes osteoblast differentiation in MC3T3-E1 preosteoblast cells. In the
      present study, the mechanism of the regulatory action of LAR on osteoblast
      differentiation was investigated. The mineralization of extracellular matrix and
      calcium accumulation in MC3T3-E1 cells were markedly enhanced by LAR
      overexpression, and these effects were further increased by treatment with a MEK
      inhibitor. In addition, LAR overexpression dramatically reduced extracellular
      signal-regulated kinase (Erk) activation during osteoblast differentiation. In
      contrast, a marginal effect of the inactive LAR mutant on Erk activation was
      detected. Expression of osteoblast-related genes such as ALP, BSP, DLX5, OCN, and
      RUNX2, was increased by LAR overexpression during osteoblast differentiation. On
      the basis of these results, we propose that LAR functions as a positive regulator
      of osteoblast differentiation by modulating ERK activation. Therefore, LAR
      phosphatase could be used as a novel regulatory target protein in many bone
      associated diseases, including osteoporosis.

PMID- 20811814
TI  - Analysis of the molecular and regulatory properties of active porcine endogenous
      retrovirus gamma-1 long terminal repeats in kidney tissues of the NIH-Miniature
      pig.
AB  - The pig genome contains the gamma 1 family of porcine endogenous retroviruses
      (PERVs), which are a major obstacle to the development of successful
      xenotransplantation from pig to human. Long terminal repeats (LTRs) found in
      PERVs are known to be essential elements for the control of the transcriptional
      activity of single virus by different transcription factors (TFs). To identify
      transcribed PERV LTR elements, RT-PCR and DNA sequencing analyses were performed.
      Twenty-nine actively transcribed LTR elements were identified in the kidney
      tissues of the NIH-Miniature pig. These elements were divided into two major
      groups (I and II), and four minor groups (I-1, I-2, I-3, and II-1), by the
      presence of insertion and deletion (INDEL) sequences. Group I elements showed
      strong transcriptional activity compared to group II elements. Four different LTR
      elements (PL1, PL2, PL3, and PL4) as representative of the groups were analyzed
      by using a transient transfection assay. The regulation of their promoter
      activity was investigated by treatment with M.SssI (CpG DNA methyltransferase)
      and garcinol (histone acetyltransferase inhibitor). The transcriptional activity
      of PERV LTR elements was significantly reduced by treatment with M.SssI. These
      data indicate that transcribed PERV LTR elements harbor sufficient promoter
      activity to regulate the transcription of a single virus, and the transcriptional
      activity of PERV LTRs may be controlled by DNA methylation events.

PMID- 20811815
TI  - (E)-1-(3,4-dihydroxyphenethyl)-3-styrylurea inhibits proliferation of MCF-7 cells
      through G1 cell cycle arrest and mitochondria-mediated apoptosis.
AB  - Growing interest in the beneficial effects of antioxidants has inspired the
      synthesis of new phenolic acid phenethyl ureas (PAPUs) with enhanced antioxidant
      potential. We have previously shown the capacity of one PAPU compound, (E)-1-(3,4
      dihydroxyphenethyl)-3-styrylurea (PAPU1), to induce caspase-dependent apoptosis
      in melanoma cells. In the present study, we examined the anti-proliferative
      effects of PAPU compounds on MCF-7 human breast cancer cells and determined the
      molecular mechanisms involved. Treatment with PAPU compounds inhibited
      predominantly proliferation in these cells, where the PAPU1 was the most
      efficient form. Flow cytometric analysis showed that PAPU1 blocked cell cycle
      progression in the G(0)/G(1) phase, and reduced the proportion of cells in G(2)/M
      phase. This was related to the inhibition of cell cycle regulatory factors,
      including cyclin D/E and cyclin-dependent kinase (CDK) 2/4, through induction of
      p21(Cip1). PAPU1 also induced the mitochondrial-mediated and caspase-dependent
      apoptosis in MCF-7 cells. This was evidenced by cellular changes in the levels of
      Bcl-2 and Bax, loss of the mitochondrial membrane potential, release of
      cytochrome c into the cytosol, and caspase-9 activation. Collectively, our
      results suggest that G(1) cell cycle regulatory proteins and mitochondrial
      pathways are the crucial targets of PAPU1 in the chemoprevention of breast cancer
      cells.

PMID- 20811816
TI  - Mutual interferences and design principles for mechatronic devices in magnetic
      resonance imaging.
AB  - PURPOSE: Robotic and mechatronic devices that work compatibly with magnetic
      resonance imaging (MRI) are applied in diagnostic MRI, image-guided surgery,
      neurorehabilitation and neuroscience. MRI-compatible mechatronic systems must
      address the challenges imposed by the scanner's electromagnetic fields. We have
      developed objective quantitative evaluation criteria for device characteristics
      needed to formulate design guidelines that ensure MRI-compatibility based on
      safety, device functionality and image quality. METHODS: The mutual interferences
      between an MRI system and mechatronic devices working in its vicinity are modeled
      and tested. For each interference, the involved components are listed, and a
      numerical measure for "MRI-compatibility" is proposed. These interferences are
      categorized into an MRI-compatibility matrix, with each element representing
      possible interactions between one part of the mechatronic system and one
      component of the electromagnetic fields. Based on this formulation, design
      principles for MRI-compatible mechatronic systems are proposed. Furthermore, test
      methods are developed to examine whether a mechatronic device indeed works
      without interferences within an MRI system. Finally, the proposed MRI
      compatibility criteria and design guidelines have been applied to an actual
      design process that has been validated by the test procedures. RESULTS: Objective
      and quantitative MRI-compatibility measures for mechatronic and robotic devices
      have been established. Applying the proposed design principles, potential
      problems in safety, device functionality and image quality can be considered in
      the design phase to ensure that the mechatronic system will fulfill the MRI
      compatibility criteria. CONCLUSION: New guidelines and test procedures for MRI
      instrument compatibility provide a rational basis for design and evaluation of
      mechatronic devices in various MRI applications. Designers can apply these
      criteria and use the tests, so that MRI-compatibility results can accrue to build
      an experiential database.

PMID- 20811818
TI  - Is maintenance rituximab now ready for PRIMA-time?

PMID- 20811817
TI  - Wnt/beta-catenin is involved in the proliferation of hippocampal neural stem
      cells induced by hypoxia.
AB  - BACKGROUND AND AIM: Beta-catenin, as a major effector molecule in the canonical
      Wnt signaling pathway, could regulate adult neurogenesis. Here, the role of
      Wnt/beta-catenin signaling pathway in the proliferation of hippocampal neural
      stem cells (NSCs) induced by hypoxia was investigated. METHODS: The hippocampal
      NSCs of neonatal green fluorescent protein transgenic mice on day 0 were cultured
      in hypoxia (5% O(2)) and traditional O(2) (20% O(2)). The expression of beta
      catenin, p-GSK-3beta, and cyclinD1 in NSCs was measured under hypoxia or
      traditional O(2) by western blotting. NSCs were electroporated with pTOPFLASH
      reporter in different conditions and the LEF/TCF-dependent luciferase activity
      was assayed. RESULTS: Hypoxia increased the proliferation and reduced the
      apoptosis of hippocampal NSCs. NSCs proliferation was inhibited by transfecting
      with pAxin, whereas promoted by transfecting with pbeta-catenin. CONCLUSION:
      Hypoxia could enhance the proliferation of hippocampal NSCs and beta-catenin
      contributed to this action.

PMID- 20811819
TI  - Evaluating patient satisfaction with the Office of Patient Advocacy.
AB  - Patient satisfaction is an important indicator of healthcare quality. Blood and
      marrow transplantation is a complex but potentially curative procedure for
      patients with life-threatening hematologic disorders. The Office of Patient
      Advocacy provides services and health education materials to transplant patients,
      caregivers, and family members. Satisfaction surveys help identify the specific
      needs of patients. This article reports findings from surveys administered to
      patients and family members. Key evaluation areas included: helpfulness of
      information and services provided and overall satisfaction with Coordinator
      services. Respondents were asked to describe follow-up actions taken as a result
      of the information/services provided and to recommend ways to improve these
      services. Transplant patients face complex treatment with high risks of
      morbidity, which may impact likelihood of survey response. The findings indicate
      that satisfied respondents were more likely to self advocate through follow-up
      actions. Respondent feedback was useful for improving Office of Patient Advocacy
      services.

PMID- 20811820
TI  - There are still some things money can't buy.

PMID- 20811821
TI  - Reproductive health after cancer.

PMID- 20811822
TI  - Designing follicle-environment interactions with biomaterials.

PMID- 20811823
TI  - Gamete preservation.

PMID- 20811824
TI  - To transplant or not to transplant - that is the question.

PMID- 20811825
TI  - Clinical cases in oncofertility.

PMID- 20811826
TI  - Cancer genetics: risks and mechanisms of cancer in women with inherited
      susceptibility to epithelial ovarian cancer.

PMID- 20811827
TI  - Protecting and extending fertility for females of wild and endangered mammals.

PMID- 20811828
TI  - Placing the history of oncofertility.

PMID- 20811829
TI  - Medical hope, legal pitfalls: potential legal issues in the emerging field of
      oncofertility.

PMID- 20811830
TI  - Domestic and international surrogacy laws: implications for cancer survivors.

PMID- 20811831
TI  - Adoption after cancer: adoption agency attitudes and perspectives on the
      potential to parent post-cancer.

PMID- 20811832
TI  - Ovarian tissue cryopreservation and bioethical discourse.

PMID- 20811833
TI  - The lessons of oncofertility for assisted reproduction.

PMID- 20811834
TI  - Morally justifying oncofertility research.

PMID- 20811835
TI  - Ethical dilemmas in oncofertility: an exploration of three clinical scenarios.

PMID- 20811836
TI  - Participation in investigational fertility preservation research: a feminist
      research ethics approach.

PMID- 20811837
TI  - Reproductive 'choice' and egg freezing.

PMID- 20811838
TI  - The impact of infertility: why ART should be a higher priority for women in the
      global South.

PMID- 20811839
TI  - Oncofertility and informed consent: addressing beliefs, values, and future
      decision making.

PMID- 20811840
TI  - Bioethics and oncofertility: arguments and insights from religious traditions.

PMID- 20811841
TI  - Sacred bodies: considering resistance to oncofertility in muslim communities.

PMID- 20811842
TI  - Unlikely Motherhood in the Qur'an: oncofertility as devotion.

PMID- 20811843
TI  - Technology and wholeness: oncofertility and Catholic tradition.

PMID- 20811844
TI  - Jewish perspectives on oncofertility: the complexities of tradition.

PMID- 20811845
TI  - The oncofertility saturday academy: a paradigm to expand the educational
      opportunities and ambitions of high school girls.

PMID- 20811846
TI  - MyOncofertility.org: a web-based patient education resource supporting decision
      making under severe emotional and cognitive overload.
AB  - Kristin, a 38-year-old female with breast cancer, was scheduled to begin
      treatment a week after receiving her diagnosis. Although she was in a four-year
      long relationship, she had never thought about having kids. Kristin was told that
      embryo banking (IVF) was the best option for fertility preservation, and she had
      to decide immediately if she wanted biological children in order to start an egg
      retrieval cycle. Because no other options were provided and she was uncertain
      about freezing embryos with her partner, she ended up foregoing fertility
      preservation prior to the treatments that ultimately left her infertile. Ethan, a
      19-year-old male, was in the hospital for four days awaiting surgery to remove a
      pelvic sarcoma. The surgery required removal of his testes rendering him
      infertile. During those four days, no one talked to him or his family about sperm
      banking, even though it could hve been accomplished in a matter of minutes.

PMID- 20811847
TI  - Anticipating ovarian tissue cryopreservation in the health-care marketplace: a
      willingness to pay assessment.

PMID- 20811848
TI  - Perspectives on oncofertility from demography and economics.

PMID- 20811849
TI  - For the sake of consistency and fairness: why insurance companies should cover
      fertility preservation treatment for iatrogenic infertility.

PMID- 20811850
TI  - Healthcare provider perspectives on fertility preservation for cancer patients.

PMID- 20811851
TI  - Counseling and consenting women with cancer on their oncofertility options: a
      clinical perspective.

PMID- 20811852
TI  - The fertility-related treatment choices of cancer patients: cancer-related
      infertility and family dynamics.

PMID- 20811853
TI  - Whose future is it? Ethical family decision making about daughters' treatment in
      the oncofertility context.

PMID- 20811854
TI  - Choosing life when facing death: understanding fertility preservation decision
      making for cancer patients.

PMID- 20811855
TI  - Discussing fertility preservation with breast cancer patients.

PMID- 20811856
TI  - Warning: google can be hazardous to your health: fertility preservation is an
      important part of cancer care.

PMID- 20811857
TI  - The role of a patient navigator in fertility preservation.

PMID- 20811858
TI  - Judaism and reproductive technology.

PMID- 20811859
TI  - Reading between the lines of cancer and fertility: a provider's story.

PMID- 20811860
TI  - A rewarding experience for a pediatric urologist.

PMID- 20811861
TI  - Final thoughts.

PMID- 20811862
TI  - Atmospheric perfluorinated acid precursors: chemistry, occurrence, and impacts.
AB  - Perfluorocarboxylic acids (PFCAs) can be found from the hydrolysis of
      perfluoroacyl fluorides and chlorides, which can be produced in three separate
      ways in the atmosphere. Alternatively, PFCAs can be formed directly in the gas
      phase through reaction of perfluoroacyl peroxy radicals or perfluorinated
      aldehyde hydrates. All five mechanisms have been elucidated using smog chamber
      techniques. Yields of the PFCAs from this process vary from less than 10% to
      greater than 100%, depending on the mechanism. The formation of perfluorosulfonic
      acids in the atmosphere can also occur, though the mechanism has not been
      entirely elucidated. A large number of compounds have been confirmed as
      perfluorinated acid precursors, including CFC-replacement compounds, anesthetics,
      fluorotelomer compounds, and perfluorosulfonamides. Levels of some of these
      compounds have been measured in the atmosphere, but concentration for the
      majority have yet to be detected. It is clear that atmospheric oxidation of
      volatile precursors contributes to the overall burden of PFAs, though the extent
      to which this occurs is compound and environment dependent and is difficult to
      assess accurately.

PMID- 20811863
TI  - Isomer profiling of perfluorinated substances as a tool for source tracking: a
      review of early findings and future applications.
AB  - The two major manufacturing techniques for perfluorochemicals can be
      distinguished based on the isomeric profile of their products. ECF (major use
      from 1950s to 2002) results in a product containing both linear and branched
      isomers, while telomerization (major use from 2002 to present) typically yields
      an isomerically pure, linear product. Among the most important question today,
      which has implication for future regulation of these chemicals, is to what extent
      human and environmental exposure is from historical products (i.e., ECF) versus
      currently manufactured fluorochemicals (i.e., telomer). Perfluoroalkyl-chain
      branching can also affect the physical and chemical properties of these
      chemicals, which may influence their environmental transport and degradation,
      partitioning, bioaccumulation, pharmacokinetics, and toxicity. Unless
      perfluorinated substances are considered as individual isomers, much of this
      information will be overlooked or missed altogether, which could potentially lead
      to inaccuracies in human and environmental risk assessments. In this review, we
      have highlighted novel findings, current knowledge gaps, and areas for
      improvement based on early experiments on the disposition of PFA and PFA
      precursor isomers in the environment. We have also emphasized the wealth of
      information that can potentially be gleaned from future work in this area, which
      renders routine adoption of isomer-specific methodologies an attractive and
      logical next step in the progression of fluorochemicals analysis. However,
      despite vast improvements in recent years, a fast and comprehensive method
      capable of separating all major PFA and PFA-precursor isomers, while removing
      interferences is still required before these methods becomes routine in most
      labs. Purified and characterized standards of PFOA and PFOS that have isomer
      profiles consistent with those of historically produced (i.e., 3M) PFOS and PFOA
      are also required. The limited data available on PFA isomer profiles that exist
      in the environment and the biological properties of each isomer suggest that
      examination of isomer profiles may yield clues on the source of PFA contamination
      to human and the environment. For example, contributions from historical versus
      current PFOA emissions can be quantified by examining the isomer profile in
      abiotic samples . Similarly, residual PFOS/PFOA in pre-2002 consumer products may
      be distinguished from directly emitted PFOS/PFOA by the existence of slight
      difference in isomer profile. PFOS signatures may also have the potential to
      distinguish between indirect exposure (via precursors) versus direct exposure
      (via the sulfonate), based on findings of isomer-specific and/or enantiospecific
      biotransformation in vitro. Isomer-specific monitoring extended to longer-chain
      PFAs may also be informative in determining current and historical exposure
      sources. Finally, given the recent increase of production of PFOSF-based
      chemicals, following their 2002 phase out, the ability of using isomer profiles
      to distinguish between historical and currently produced PFOS may also be
      possible.

PMID- 20811864
TI  - Biodegradation of fluorinated alkyl substances.
AB  - The incorporation of fluorine into organic molecules entails both positive and
      adverse effects. Although fluorine imparts positive and unique properties such as
      water-and oil-repellency and chemical stability, adverse effects often pervade
      members of this compound class. A striking property of long perfluoroalkyl chains
      is their very pronounced environmental persistence. The present review is the
      first one designed to summarize recent accomplishments in the field of
      biodegradation of fluorine-containing surfactants, their metabolites, and
      structural analogs. The pronounced scientific and public interest in these
      chemicals has given impetus to undertake numerous degradation studies to assess
      the sources and origins of different fluorinated analog chemical known to exist
      in the environment. It was shown that biodegradation plays an important role in
      understanding how fluorinated substances reach the environment and, once they do,
      what their fate is. Today, PFOS and PFOA are ubiquitously detected as
      environmental contaminants. Their prominence as contaminants is mainly due to
      their extreme persistence, which is linked to their perfluoroalkyl chain length.
      It appears that desulfonation of a highly fluorinated surfactants can be achieved
      if an alpha-situated H atom, in relation to the sulfonate group, is present, at
      least under sulfur-limiting conditions. Molecules that are less heavily
      fluorinated can show very complex metabolic behavior, as is the case for
      fluorotelomer alcohols. These compounds are degraded via different but
      simultaneous pathways, which produce different stable metabolites, one of which
      is the respective perfluoroalkanoate (8:2-FTOH is transformed to PFOA).
      Preliminary screening tests indicate that fluorinated functional groups, such as
      the trifluoromethoxy group and the p-(trifluoromethyl)phenoxy group, may be
      useful implementations in novel, environmentally benign fluorosurfactants. More
      specifically, trifluoromethoxy groups constitute a substitute for those that have
      been used in the past; this functionality is degradable when it appears in
      structures that are normally subject to biodegradation. Other compounds tested
      did not meet this criterion. Interdisciplinary investigations on fluorinated
      surfactants are still very much needed and will certainly continue during the
      next many years. For instance, the role of fluorinated polymers in contributing
      small fluorinated molecules to the environmental burden still has not been fully
      understood.

PMID- 20811865
TI  - Perfluorinated substances in human food and other sources of human exposure.
AB  - The widespread distribution and degradation of PFCs in the environment results in
      a very complex exposure pattern, which makes it difficult to define the relative
      contribution to human exposure from different exposure pathways. The present
      review is designed to provide an overview of the existing data on levels of PFCs
      measured in the human diet and in drinking water. Data on levels of PFCs in the
      human diet are rather scarce, but the level in the fish appear to be well
      documented. Among PFCs, PFOS and PFOA are the best studied compounds in fish from
      both experimental and monitoring studies. Recently, the number of publications
      that address other PFCs has increased, but the total number available is still
      limited. In general, we discovered that care should be exercised when using the
      reviewed data, because, in the majority of publications, quality control and/or
      details on analysis are, at least partly, lacking. It has been well documented
      that PFOA and PFOS have the potential to accumulate in fish and concentrations up
      to 7 and 170 ng/g wwt, respectively in edible fish species have been found. PFOS
      is the most crucial and prominent compound identified, followed by the PFOA.
      Also, in aquatic invertebrate such as shrimps, mussels, clams, and oysters, high
      PFOS levels have been reported (up to 387 ng/g wwt). However in most publications
      PFC level reported in molluscs were less than 1 ng/g wwt. Positive correlations
      were found between PFC body burden and self reported fish consumption. In
      recognition of the potential for human exposure to PFCs via fish consumption, the
      Minnesota Department of Health has recently issued fish consumption advisories
      for contaminated sections of the Mississippi River. It is interesting to note
      that 79% of the reviewed publications on PFCs in the whole fish homogenates
      exceed the that threshold. Moreover, five of the PFC concentration reported in
      muscles tissue exceeded the advisory level of 38 ng/g wwt. Even though several
      authors concluded that consumption of contaminated food and drinking water
      constitutes the major exposure pathway for humans, only a few reports on PFCs in
      composite food exist. Food can be contaminated in an indirect way, because PFCs
      are widely used in food-packaging coatings and cooking materials. On the other
      hand, PFCs can also enter food organisms via environmental routes such as
      inhalation or adsorption from air. In a few studies, composite samples, duplicate
      diet samples, or other food items were analyzed for several PFCs, PFOS and PFOA,
      PFHpA, PFHxA, and PFHxS were meAsured and displayed concentrations ranging from
      detected up to 15 ng/g wwt. In one study, a very high PFOA concentration of 118
      ng/g were reported, but overall, PFC levels are below 10 ng/g wwt. It is
      important to note that, among all studies reviewed, PFCs were found in a maximum
      of 50% of the analyzed samples and generally only in 10% or less of samples
      analyzed. In contrast to what is observed in fish and other food items PFOA
      levels in drinking water (ND - 50 ng/L) and other PFCs (1-3 ng/L). In one study,
      extremely high values (519 ng/L) were measured in drinking water of a
      contaminated area in the Ruhr region. In Spain, bottled water was analyzed and
      four PFCs (PFOA, PFNA,PFDA and PFHpA) were found at low levels (<1 ng/L). Because
      of higher levels found in drinking water at several locations, some provisional
      drinking water guideline values for PFOS and PFOA have already been established,
      e.g., in the UK, Bavaria, and Minnesota. Since PFCs are present both in food and
      drinking water, Tolerable Daily Intake values for PFOS and PFOA have also been
      proposed by several institutes in Europe and in the USA. The ingestion of dust
      through hand-to-mouth transfer from indoor house dust can also be a potential
      source of PFC exposure, especially for toddlers and children. In publications on
      PFCs in indoor dust, the mean PFOS and PFOA levels varied between 39 and 1,200
      ng/g and between 11 and 220 ng/g, respectively. Overall, it is clear that there
      is still lack of PFC exposure data for food and beverages, which renders the
      assessment of the contribution of the diet to total human PFC exposure uncertain.
      It is, therefore, appropriate that several scientific projects have recently been
      launched that addresses the assessment of human exposure to PFCs and related
      compounds from dietary sources.

PMID- 20811866
TI  - [Hearing aids, implantable hearing aids and cochlear implants in chronic tinnitus
      therapy].
AB  - Chronic tinnitus can be influenced positively by plastic cortical changes of
      tinnitus assignment and auditory perception. Acoustic stimulation plays an
      important role, either through active hearing therapy or through a hearing
      device. The positive effect of hearing aids regarding tinnitus loudness and
      severity has been shown in many studies with large numbers of patients and
      amounts to up to 70%. Implantable hearing systems and their effect on tinnitus
      have not been examined sufficiently yet; there are reports about positive as well
      as negative effects on tinnitus perception. There is a strong indication,
      however, when pathological processes in the middle ear need direct coupling of
      the implantable hearing aid with the stapes or the round window and there is no
      possibility of providing a conventional hearing aid due to high-grade combined
      hearing loss. Cochlear implants (CI) for profoundly deaf patients influence
      tinnitus loudness and severity in 34-93% of the patients; the large deviation is
      due to inhomogeneous parameters in the studies that are not always based on
      validated questionnaires. Existing tinnitus, however, influences the outcome of
      CI patients. There are studies and discussions about the effect of CI for
      unilateral deafness with tinnitus.

PMID- 20811867
TI  - [Pharmacotherapy of acute and chronic hearing loss].
AB  - The aetiology of acute hearing loss is mostly idiopathic like sudden
      sensorineural hearing loss and rarely infectious or vascular. Several studies and
      meta-analyses of pharmacotherapy are reviewed: In chronic tinnitus there is no
      indication for pharmacotherapy; sometimes a possible psychosomatic comorbidity
      has to be treated with psychopharmaceutical agents. Despite a low level of
      evidence treatment with steroids and initially plasma expanding infusions is
      recommended for acute tinnitus if there is no spontaneous remission.
      Intratympanic steroid therapy can be used as an alternative if there is severe
      hearing loss together with tinnitus.

PMID- 20811868
TI  - [Molecular biological aspects of neuroplasticity: approaches for treating
      tinnitus and hearing disorders].
AB  - Peripheral and central structures are involved in the onset of tinnitus. Neuronal
      plasticity is of special importance for the occurrence of central tinnitus and
      its persistent form. Neuronal plasticity is the ability of the brain to adapt its
      own structure (synapses, nerve cells, or even whole areas of the brain) and its
      organization to modified biological requirements. Neuroplasticity is an ongoing
      dynamic process. Generally speaking, there are two types of plasticity: synaptic
      and cortical. Cortical plasticity involves activity-dependent changes in size,
      connectivity, or in the activation pattern of cortical networks. Synaptic
      plasticity refers to the activity-dependent change in the strength of synaptic
      transmission and can affect both the morphology and physiology of the synapse.
      The stimulation of afferent fibers leads to long-lasting changes in synaptic
      transmission. This phenomenon is called long-term potentiation (LTP) or long-term
      depression (LTD). From the perspective of molecular biology, synaptic plasticity
      is of particular importance for the development of tinnitus and its persistence.
      Ultimately, the damage to the hair cells, auditory nerve, and excitotoxicity
      results in an imbalance between LTP and LTD and thus in changes of synaptic
      plasticity. After excessive acoustic stimulation, LTP can be induced by the
      increase of afferent inputs, whereas decreased afferent inputs generate LTD. The
      imbalance between LTP and LTD leads to changes in gene expression and involves
      changes in neurotransmission, in the expression of the receptors, ion channels,
      regulatory enzymes, and in direct changes on the synapses. This causes an
      increase of activity on the cellular level. As a result, the imbalance can lead
      to hyperactivity in the dorsal cochlear nucleus, inferior colliculus, and in the
      auditory cortex and, later on, to changes in cortical plasticity leading to
      tinnitus.

PMID- 20811869
TI  - [Auditory processing and perception disorders--diagnostics. Guidelines of the
      German Society of Phoniatrics and Pedaudiology].

PMID- 20811870
TI  - [Tinnitus and psychiatric comorbidities].

PMID- 20811871
TI  - Is the flower fluorescence relevant in biocommunication?
AB  - Flower fluorescence has been previously proposed as a potential visual signal to
      attract pollinators. In this work, this point was addressed by quantitatively
      measuring the fluorescence quantum yield (Phi(f)) for flowers of Bellis perennis
      (white, yellow, pink, and purple), Ornithogalum thyrsoides (petals and ovaries),
      Limonium sinuatum (white and yellow), Lampranthus productus (yellow), Petunia
      nyctaginiflora (white), Bougainvillea spectabilis (white and yellow), Antirrhinum
      majus (white and yellow), Eustoma grandiflorum (white and blue), Citrus aurantium
      (petals and stigma), and Portulaca grandiflora (yellow). The highest values were
      obtained for the ovaries of O. thyrsoides (Phi(f) = 0.030) and for Citrus
      aurantium petals (Phi(f) = 0.014) and stigma (Phi(f) = 0.013). Emitted photons as
      fluorescence were compared with reflected photons. It was concluded that the
      fluorescence emission is negligible compared to the reflected light, even for the
      most fluorescent samples, and it may not be considered as an optical signal in
      biocommunication. The work was complemented with the calculation of quantum
      catches for each studied flower species to describe the visual sensitization of
      eye photoreceptors.

PMID- 20811872
TI  - [From SPACE to CREST: whoever has the choice also has the torment].

PMID- 20811875
TI  - Unicondylar osteoarticular allograft reconstruction of the distal femur in a
      patient with a traumatic osteoaticular defect of the lateral femoral condyle.
AB  - PURPOSE: The objective of this study was to report the clinical results for a
      patient with a post-traumatic osteoarticular defect of the lateral femoral
      condyle treated with unicondylar osteoarticular allograft reconstruction. METHOD:
      We describe the case with a massive osteoarticular loss of the lateral femoral
      condyle combined with a grade IIIA open distal femoral diaphyesal fracture. The
      patient underwent unicondylar osteoarticular reconstruction with an allogenic
      fresh-frozen condyle. RESULTS: There were no complications after the
      reconstructive procedure. At the five year follow-up, the patient showed a
      favorable clinical outcome with a full range of motion of the knee joint.
      Degenerative changes were seen in the graft compartment, but they did not cause
      serious functional limitations. CONCLUSION: Unicondylar allograft reconstruction
      appears to be a surgical option for patients who suffer from a post-traumatic
      distal femoral osteoarticular defect in which only one condyle is absent or
      severely damaged.

PMID- 20811874
TI  - The role of vasoactive agents in the resuscitation of microvascular perfusion and
      tissue oxygenation in critically ill patients.
AB  - PURPOSE: The clinical use of vasoactive drugs is not only intended to improve
      systemic hemodynamic variables, but ultimately to attenuate derangements in organ
      perfusion and oxygenation during shock. This review aims (1) to discuss basic
      physiology with respect to manipulating vascular tone and its effect on the
      microcirculation, and (2) to provide an overview of available clinical data on
      the relation between vasoactive drugs and organ perfusion, with specific
      attention paid to recent developments that have enabled direct in vivo
      observation of the microcirculation and concepts that have originated from it.
      METHODS: A MedLine search was conducted for clinical articles in the English
      language over the last 15 years pertainig to shock, sepsis, organ failure, or
      critically ill patients in combination with vasoactive drugs and specific
      variables of organ perfusion/oxygenation (e.g., tonometry, indocyanine clearance,
      laser Doppler, and sidestream dark field imaging). RESULTS: Eighty original
      papers evaluating the specific relationship between organ perfusion/oxygenation
      and the use of vasoactive drugs were identified and are discussed in light of
      physiological theory of vasomotor tone. CONCLUSIONS: Solid clinical data in
      support of the idea that increasing blood pressure in shock improves
      microcirculatory perfusion/oxygenation seem to be lacking, and such a concept
      might not be in line with physiological theory of microcirculation as a low
      pressure vascular compartment. In septic shock no beneficial effect on
      microcirculatory perfusion above a mean arterial pressure of 65 mmHg has been
      reported, but a wide range in inter-individual effect seems to exist. Whether
      improvement of microcirculatory perfusion is associated with better patient
      outcome remains to be elucidated.

PMID- 20811876
TI  - Transpatellar approach in lateral meniscal allograft transplantation using the
      keyhole method: can we prevent graft extrusion?
AB  - PURPOSE: technique for guide wire placement during meniscal allograft
      transplantation (MAT) is usually based on the parapatellar approach that is not
      in the anatomical direction of meniscal horn bony insertions. Here, we present a
      surgical technique to achieve the correct anatomical position of the meniscal
      graft using the transpatellar approach. METHODS: a guide wire was introduced
      through the patellar tendon in the direction of the meniscal insertion sites
      passing the lateral tibial spine. The insertion plane of the guide wire was
      approximately at the medial aspect of the tibial tuberosity and slightly medial
      to the midplane of the patellar tendon. After confirmation with C-arm, the guide
      wire was cut at the level just beneath the patellar tendon. The knee was then
      brought to the extension position which lessened the tension of the patellar
      tendon and retracted it to the medial aspect to expose the end of the guide wire.
      Drilling and insertion of bone block was performed accordingly. RESULTS: eleven
      consecutive patients with total or near-total meniscectomy of the knee underwent
      MAT with the described technique. The mean extrusion taken on 1-year
      postoperative non-weight-bearing MRI was 1.6 mm (range 0.5-2.9 mm). None of the
      patients presented with symptoms requiring a secondary surgery at the time of
      review. CONCLUSION: the described technique focuses on achieving correct
      positioning of the tibia tunnel through the patellar tendon and tunnel reaming in
      the extended knee position via the mini-open parapatellar approach during lateral
      MAT. This "transpatellar approach" could be an effective method for anatomical
      placement of meniscal graft.

PMID- 20811877
TI  - Treatment choice, duration, and cost in patients with interstitial cystitis and
      painful bladder syndrome.
AB  - INTRODUCTION AND HYPOTHESIS: In order to better understand provider treatment
      patterns for interstitial cystitis (IC)/painful bladder syndrome, we sought to
      document the therapies utilized and their associated expenditures using a
      national dataset. METHODS: A cohort was created by applying the ICD-9 diagnosis
      of IC (595.1) to INGENIX claims for the year 1999. Subjects were followed for 5
      years, and patterns of care and related expenditures were evaluated. RESULTS: Of
      553,910 adults insured in 1999, 89 subjects had a diagnosis of IC with 5-year
      follow-up data. All subjects were treated with oral medication(s), 26% received
      intravesical treatments, and 22% underwent hydrodistension. Total expenditures
      per subject were $2,808. CONCLUSIONS: The majority of IC expenditures were
      attributable to oral medical therapy. Hydrodistension and intravesical
      instillations were utilized in less than 25% of patients. Hydrodistension was
      used more frequently among subjects with a new diagnosis; this may reflect its
      utilization as part of a diagnostic algorithm.

PMID- 20811878
TI  - PPI deficit induced by amphetamine is attenuated by the histamine H1 antagonist
      pyrilamine, but is exacerbated by the serotonin 5-HT2 antagonist ketanserin.
AB  - RATIONALE: Prepulse inhibition (PPI) of the startle response is a classic model
      of sensorimotor gating. Robust PPI impairments can be induced by dopamine
      agonists such as the indirect agonist amphetamine. The antipsychotic clozapine
      can attenuate PPI impairment induced by dopamine agonists. Clozapine is a complex
      drug with antagonistic effects on a variety of receptors, including serotonin and
      histamine. The relative contribution of its component actions to its efficacy is
      still unclear. OBJECTIVES: To better characterize the role of histamine and
      serotonin receptors in the modulation of PPI in rats, we studied the effects of
      the H(1) histamine antagonist pyrilamine (10, 20, and 40 mg/kg) on amphetamine
      induced (1 mg/kg) PPI deficits (Experiment 1); and the interaction of pyrilamine
      (20 mg/kg) with the 5-HT(2) antagonist ketanserin (1 and 2 mg/kg) on the
      amphetamine-induced PPI disruption (Experiment 2). METHODS: Tactile startle
      stimuli consisted of 30 PSI air-puffs. Three acoustic prepulse intensity levels
      were used: 68, 71, and 77 dB, presented on a 65-dB background noise. In both
      experiments, all animals received all drug doses and combinations with different
      counterbalanced orders. RESULTS: Pyrilamine (20 mg/kg) was effective in
      counteracting the PPI impairment caused by amphetamine administration, whereas
      ketanserin exacerbated the amphetamine-induced PPI deficit. CONCLUSIONS: Based on
      its ability to reverse amphetamine-induced PPI deficits, blockade of histamine
      H(1) receptors seems to contribute to the therapeutic effect of the antipsychotic
      clozapine. Serotonin 5-HT(2)-receptor blockade, though, does not appear to
      contribute to this effect, and may in fact detract from it.

PMID- 20811880
TI  - Application of FLIM-FIDSAM for the in vivo analysis of hormone competence of
      different cell types.
AB  - Background fluorescence derived from subcellular compartments is a major drawback
      in high-resolution live imaging, especially of plant cells. A novel technique for
      contrast enhancement of fluorescence images of living cells expressing
      fluorescent fusion proteins termed fluorescence intensity decay shape analysis
      microscopy (FIDSAM) has been recently published and is applied here to plant
      cells expressing wild-type levels of a low-abundant membrane protein (BRI1-EGFP),
      demonstrating the applicability of FIDSAM to samples exhibiting about 80%
      autofluorescence. Furthermore, the combination of FIDSAM and fluorescence
      lifetime imaging microscopy enables the simultaneous determination and
      quantification of different ligand-specific responses in living cells with high
      spatial and temporal resolution even in samples with high autofluorescence
      background. Correlation of different responses can be used to determine the
      hormone ligand competence of different cell types as demonstrated here in BRI1
      EGFP-expressing root and hypocotyl cells.

PMID- 20811879
TI  - Serotonin1A receptor deletion does not interact with maternal separation-induced
      increases in startle reactivity and prepulse inhibition deficits.
AB  - RATIONALE: Early life stress is a risk factor for the development of
      psychopathology in later life. Consequences of adverse life events, however, may
      depend on the genetic makeup of an individual. Reduced serotonin(1A) receptor
      function may predispose to the development of anxiety disorders. OBJECTIVE:
      Determine susceptibility of serotonin(1A) receptor knockout (1AKO) mice on
      different background strains to the effects of maternal separation (MS) by
      assessing startle plasticity in adulthood. METHODS: 1AKO mice on a 129S6 and a
      Swiss Webster (SW) background were used. MS groups were separated daily from
      their mother for 180 min/day from postnatal days 2 to 14. Control groups
      underwent normal animal facility rearing. In adulthood, effects on acoustic
      startle response, habituation, prepulse inhibition (PPI), and foot shock
      sensitization were determined. RESULTS: MS increased startle reactivity and
      reduced PPI in 129S6 mice. These effects of MS were independent of genotype. MS
      had no effect on the other readouts. In SW mice, MS had no consistent effect on
      startle reactivity and did not alter startle plasticity in wild type or in 1AKO
      mice. 1AKO mice did not differ from wild-type mice in startle plasticity.
      CONCLUSION: Serotonin(1A) receptor deletion does not enhance vulnerability to the
      effects of MS on startle plasticity. The life-long increase in startle reactivity
      and PPI deficit induced by MS are strain-dependent. Further, the use of startle
      reactivity and plasticity may have added value in translational studies relating
      to early life stress.

PMID- 20811881
TI  - Major pollutants in soils of abandoned agricultural land contaminated by e-waste
      activities in Hong Kong.
AB  - Polycyclic aromatic hydrocarbon (PAH), polychlorinated biphenyl (PCB),
      polybrominated diphenyl ether (PBDE) compounds and five heavy metals (cadmium,
      copper, chromium, lead, and zinc) were determined in soil samples collected from
      six sites of abandoned agricultural land affected by electronic-waste: e-waste
      dismantling workshop [EW (DW)], e-waste open burning site [EW (OBS)], e-waste
      storage [EW (S)], and agricultural (A) in the New Territories, Hong Kong.
      Persistent organic pollutants (POPs) and heavy metals were detected in all soil
      samples. EW (DW) contained the highest concentrations of PAHs, Cr, Cu, and Zn,
      whereas EW (OBS) had the highest concentrations of PCBs, PBDEs, Cd, and Pb. PAH
      at EW (DW) and EW (OBS) and PCB concentrations at EW (OBS) exceeded the target
      values of the New Dutch list, whereas Cd, Cu, Cr, Pb, and Zn levels exceeded the
      Chinese legislation for the protection of agricultural production and
      safeguarding of human health, by 3-11 times at EW (OBS) and 5-8 times at EW (DW).
      Lead at EW (OBS) and EW (DW) and Cr at EW (DW) greatly exceeded the Canadian Soil
      Quality Guidelines by 46 and 20 times and 27 times, respectively. Concentrations
      of POPs and heavy metals at EW (DW) and EW (OBS) were significantly higher than
      at EW (S) and A. It was concluded that e-waste activities led to increases of
      toxic chemicals at these abandoned agricultural land, which would hinder the
      redevelopment of the land.

PMID- 20811882
TI  - The value of multidetector computed tomography for showing the
      azygous/hemiazygous system.

PMID- 20811883
TI  - Correlation of subjective questionnaires with cardiac function as determined by
      exercise testing in a pediatric population.
AB  - BACKGROUND: Although exercise testing is an important objective method used to
      assess cardiopulmonary function, subjective assessment often is used as a proxy
      in the clinical setting. This study aimed to determine whether responses to a
      subjective functional capacity questionnaire administered to parents and patients
      in a pediatric exercise laboratory correlate with objective assessment of
      functional capacity, measured by peak oxygen consumption during maximal voluntary
      exercise testing. METHODS: Subjective questionnaire responses and exercise test
      results collected over 10 years were retrospectively analyzed. Symptoms and
      physical capabilities were assessed using a 6-point Likert scale regarding the
      ability to attend school/work, walk, climb stairs, and run, as well as the
      frequency of fatigue, palpitations, and chest pain. Values of 0 to 3 were
      considered abnormal, whereas values of 4-5 were regarded as normal. Exercise
      testing was performed on a stationary cycle ergometer with a continuous ramping
      protocol. Heart rate and oxygen saturation were continuously monitored. Blood
      pressures and electrocardiograms (ECGs) were obtained at 2-min intervals.
      Metabolic gas analysis was performed using a breath-by-breath method. The results
      of the exercise testing were normalized for body size and expressed as a
      percentage of predicted peak oxygen consumption (%pVO(2)). RESULTS: Very weak but
      statistically significant correlations (tau < 0.25; P < 0.05) between the scores
      of the school/work, walking, stair climbing, running, and fatigue items and
      %pVO(2) were found using Kendall's rank correlations. CONCLUSIONS: The subjective
      Likert scales used to assess basic physical capacity and cardiac-associated
      symptoms have limited ability to predict actual functional capacity as measured
      by %pVO(2) achieved. The very weak rank-order correlation between %pVO(2)
      achieved and the subjective reporting of the ability to attend school/work, walk,
      climb stairs, and run has low clinical significance and will not be useful in
      predicting functional capacity within the clinic setting.

PMID- 20811884
TI  - Molecular studies of microbial community structure on stained pages of Leonardo
      da Vinci's Atlantic Codex.
AB  - In 2006, after a visual inspection of the Leonardo da Vinci's Atlantic Codex by a
      scholar, active molds were reported to have been present on Codex pages showing
      areas of staining. In the present paper, molecular methods were used to assess
      the current microbiological risk to stained pages of the manuscript. Bacterial
      and fungal communities were sampled by a non-invasive technique employing
      nitrocellulose membranes. Denaturing gradient gel electrophoresis of 16 S rRNA
      gene and internal transcribed space regions were carried out to study the
      structure of the bacterial and fungal communities and band patterns were analyzed
      by the multivariate technique of principal component analysis. Any relationship
      between the presence of an active microbial community and staining was excluded.
      The presence of potential biodeteriogens was evaluated by constructing bacterial
      and fungal clone libraries, analyzing them by an operational taxonomic unit (OTU)
      approach. Among the bacteria, some OTUs were associated with species found on
      floors in clean room while others were identified with human skin contamination.
      Some fungal OTU representatives were potential biodeteriogens that, under proper
      thermo-hygrometric conditions, could grow. The retrieval of these potential
      biodeteriogens and microorganisms related to human skin suggests the need for a
      continuous and rigorous monitoring of the environmental conditions, and the need
      to improve handling procedures.

PMID- 20811885
TI  - Inhibition of metastasis of syngeneic murine melanoma in vivo and vasculogenesis
      in vitro by monoclonal antibody C11C1 targeted to domain 5 of high molecular
      weight kininogen.
AB  - Metastasis of malignant tumors is a major cause of morbidity and mortality.
      Inhibition of tumor growth in distant organs is of clinical importance. We have
      demonstrated that C11C1, a murine monoclonal antibody to the light chain region
      of high molecular weight kininogen (HK), reduces growth of murine multiple
      myeloma in normal mice and human colon cancer in nude mice. C11C1 inhibits
      angiogenesis by reducing tumor microvascular density by blocking binding of HK to
      endothelial cells. We now evaluate the anti-metastatic effect of C11C1 on C57BL/6
      mouse lung metastatic model using B16F10 melanoma cells. The tail veins of mice
      were injected with 0.5 * 10(6) cells of melanoma B16F10. One group received C11C1
      and the other received saline (control) intraperitoneally. When mice were killed
      at 28 days, 6 of 10 control mice had detectable metastatic pulmonary nodules
      which stained positive with an antibody against S-100 protein, a tumor antigen
      present in malignant melanoma cells. In the C11C1 groups, none of the mice showed
      metastatic foci in their lungs. We showed that C11C1 inhibits endothelial cell
      tube formation in a 3-D collagen fibrinogen gel model by inhibiting the rate of
      cleavage of HK by plasma kallikrein without changing the binding affinity for HK.
      These studies demonstrate that a monoclonal antibody to HK has the potential to
      prevent metastasis with minimal side effects.

PMID- 20811886
TI  - Genetic variations and haplotypes in TIM-3 gene and the risk of gastric cancer.
AB  - PURPOSE: T cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3)
      could weaken the Th1-mediated anti-tumor responses and accelerate the tumor cell
      proliferation by inhabiting the production of IL-2 or IFN-gamma. This study was
      to assess the association between TIM-3 genetic variations and the development of
      gastric cancer. PATIENTS AND METHODS: Five polymorphisms located in the promoter
      or encoding region of TIM-3 gene were genotyped in 212 gastric cancer patients
      and 252 controls who matched with the patients on the frequency of age, gender,
      smoking, and drinking. Logistic regression was used to determine whether the
      inherited variations within TIM-3 gene were associated with gastric cancer risk.
      Linkage disequilibrium and Haplotype analyses were performed by using SHEsis
      program. RESULTS: By the individual genotype analysis, three polymorphisms (
      574G/T, -882C/T, and -1516G/T) within TIM-3 gene were significantly associated
      with gastric cancer in the study population [ORs (95% CIs): 2.74 (1.21-6.20),
      3.19 (1.29-7.91), and 2.03 (1.15-3.59); respectively]. Among the gastric cancer
      patients, the relationship between the -1516 polymorphic genotype and the distant
      metastasis of tumor was found (OR = 2.21, 95% CI = 1.05-4.63). Under the analysis
      of haplotypes, an even stronger association with haplotype TTGCT was observed in
      gastric cancer risk (OR = 5.57, 95% CI: 1.04-29.80, P = 0.024). CONCLUSION: These
      results indicated that the three genetic variations within the TIM-3 gene
      promoter may be associated with the increased susceptibility to gastric cancer,
      especially among the haplotypes with the risk.

PMID- 20811887
TI  - Practical perioperative pinnaplasty preparation.
AB  - Creating and maintaining a sterile operative field for pinnaplasty can be
      difficult. Drapes can slip, and stray hairs can interfere with delicate
      dissection and suturing. Methods to combat this have been suggested in the
      literature, but each has disadvantages, either in cost or in adequacy of surgical
      access. This report describes a practical and prudent technique for reducing
      contamination and obstruction by stray hairs in the operative field during
      performance of a pinnaplasty while maintaining adequate access at no added cost.

PMID- 20811888
TI  - Surgery Facilities Resources, Inc./AAAASFI expands international accreditation
      into new markets.

PMID- 20811890
TI  - Stent-assisted coil embolization of a mycotic renal artery aneurysm by use of a
      self-expanding neurointerventional stent.
AB  - Mycotic aneurysms are uncommon, especially those located in visceral arteries. We
      present a case of a patient with two visceral mycotic aneurysms due to bacterial
      endocarditis, one located in right upper pole renal artery and the second in the
      splenic artery. Both aneurysms were treated as endovascular embolization using
      microcoils. In the aneurysm located at the renal artery, the technique of stent
      assisted coils embolization was preferred to avoid coils migration due to its
      wide neck. The stent used was the Solitaire AB, which was designed for the
      treatment of intracranial aneurysms and was used recently in acute stroke as a
      mechanical thrombectomy device. Complete embolization of the aneurysm was
      achieved, preserving all the arterial branches without nephrogram defects in the
      final angiogram.

PMID- 20811891
TI  - Further data about upper extremity ports.

PMID- 20811892
TI  - The surgical importance of an axillary arch in sentinel node biopsy.
AB  - PURPOSE: When Carl Langer described the aberrant axillary arch in 1846 its
      relevance in sentinel node biopsy (SNB) surgery could not have been contemplated.
      The authors define an incidence and elucidate relevance of the arch in SNB of the
      axilla. METHODS: A review of a database for breast and melanoma axillary SNB was
      carried out. The sample was 1 year at Princess Margaret Hospital, Toronto.
      RESULTS: Of 319 axillary SNB, 3 (0.9%) had axillary arches noted. Two were in the
      melanoma group (n = 59) and one in the breast (n = 260). Interestingly one arch
      case had an ipsilateral 'idiopathic' axillary vein thrombosis as a child.
      CONCLUSIONS: The authors see no reason to deviate from the practice of division
      of the arch at the highest level when recognised at SNB. This would abrogate the
      risk of concealed nodes and possible future neurovascular compression.

PMID- 20811893
TI  - Comparative study of femoral diaphyseal morphometry in two male populations, in
      France and a French West Indies island: an example of clinical relevance of
      comparative anatomy for orthopedic practice.
AB  - Our aim, through a comparative study of two populations, one European and the
      other Afro-Caribbean, was to find out whether there were differences in
      radiographic measurements of femoral diaphyseal canal diameter, thickness of the
      medial and lateral cortex, and global diaphyseal diameter. We studied the nailed
      femurs of adult males in a population of 54 Europeans and 52 Afro-Caribbeans.
      Both populations were comparable in terms of age, height and weight. The
      measurements were taken with a ruler on the narrowest area of the hourglass, the
      isthmus, on an antero-posterior radiograph. The diameter of the femoral canal was
      classified into three intervals: <13 mm, 13-14 mm and >14 mm. The femoral canal
      diameter was significantly larger in the European patients, 14.3 (11-19) versus
      13.4 (11-15.6), while the thickness of the lateral cortex was significantly
      larger in the Afro-Caribbean patients, 8.50 (6-12) versus 7.72 (5.4-11.5).
      Patient distribution according to the intervals was different in both groups: 59%
      of the Afro-Caribbeans were in the average interval versus 24.1% of the
      Europeans. For nearly 53.7% of the Europeans, the diameter of the femoral canal
      fell in the last interval versus 15.4% of the Afro-Caribbeans. The fact that the
      femoral canal is narrower in the Afro-Caribbean population may be linked to a
      thicker lateral cortex. The diameters of the nails used were larger in the
      European population, 12.6 mm (10-15) versus 12.1 mm (11-14) in the Afro-Caribbean
      population. The global diameters of both populations' femurs were similar (28.9
      mm for the European sample vs. 29 mm). The present study may have an impact on
      the implants used in the orthopedic surgery (intramedullary nailing, arthroplasty
      implants). The range of usable implants must be complete and there must be
      precise pre-operative planning. A study of computed tomography scans could
      complement our measurements.

PMID- 20811894
TI  - Phase I/II study of a combination of docetaxel, capecitabine, and cisplatin (DXP)
      as first-line chemotherapy in patients with advanced gastric cancer.
AB  - BACKGROUND: This study was conducted to determine the optimal dosage of the
      docetaxel-capecitabine-cisplatin (DXP) regimen and to evaluate its efficacy and
      safety in patients with advanced gastric cancer. METHODS: Patients with advanced
      gastric or esophagogastric junctional adenocarcinoma received capecitabine (days
      1-14) and intravenous docetaxel and cisplatin (day 1) every 3 weeks. RESULTS: In
      the phase I study, 15 patients were treated with 4 different dose levels.
      Asthenia and neutropenic fever were the dose-limiting toxicities. For the phase
      II study, 1,125 mg/m(2) of capecitabine was initially recommended with 60 mg/m(2)
      docetaxel and 60 mg/m(2) cisplatin. However, frequent dose modifications at this
      dose level resulted in a final optimal dose of 937.5 mg/m(2) capecitabine. Among
      the 40 patients enrolled in the phase II study, 4 complete and 23 partial
      responses were observed, presenting objective response rate of 68%. Ten patients
      achieving good response with complete disappearance of distant metastases
      underwent surgery, and 4 pathologic complete responses were identified. After the
      median follow-up of 83.7 months (range, 20.2-86.5) in surviving patients, the
      median overall survival was 14.4 months and median progression-free survival was
      7.6 months. The most frequent grade 3/4 adverse events were neutropenia (62.5%)
      and asthenia (37.5%). Ten per cent of the patients experienced neutropenic fever,
      with one case of sepsis-induced death. CONCLUSION: DXP displays considerable
      antitumor activity, and may thus present effective first-line treatment for
      advanced gastric cancer. Further investigation of the efficacy and safety of this
      regimen in both first-line and neoadjuvant settings is warranted.

PMID- 20811895
TI  - A multi-institution phase II study of gemcitabine/S-1 combination chemotherapy
      for patients with advanced biliary tract cancer.
AB  - PURPOSE: We aimed to evaluate the efficacy and safety of gemcitabine/S-1
      combination chemotherapy for the treatment of patients with advanced biliary
      tract cancer. METHODS: Patients with histologically or cytologically confirmed
      unresectable or recurrent biliary tract cancer were eligible for inclusion. The
      primary endpoint was overall survival. Gemcitabine was administered intravenously
      at a dose of 1,000 mg/m(2) over 30 min on days 1 and 8, and oral S-1 was
      administered daily at a dose of 60 mg/m(2) on days 1-14. This schedule was
      repeated every 3 weeks until disease progression or patient refusal. RESULTS:
      Twenty-five patients were enrolled between October 2007 and January 2009. Eleven
      patients (44%) had extrahepatic bile duct cancer, 5 (20%) had intrahepatic bile
      duct cancer, 8 had gallbladder cancer (32%), and 1 (4%) had ampulla of Vater
      cancer. The median overall survival time was 12.7 months (95% CI, 8.4-23.5
      months), and the 1-year survival rate was 52.0% (95% CI, 31.2-69.2%). Of the 23
      patients with evaluable target regions, seven patients experienced a partial
      response, and an overall response rate was 30.4%. The following grade 3-4
      hematological toxicities occurred: neutropenia (56%), leukopenia (24%), anemia
      (8%) and thrombocytopenia (4%). In spite of the high incidence of grade 3-4
      neutropenia, no patients developed febrile neutropenia in the present study. The
      major grade 3-4 non-hematological toxicities were fatigue (8%), anorexia (8%) and
      diarrhea (4%). CONCLUSIONS: Gemcitabine/S-1 combination chemotherapy offered a
      promising survival benefit with acceptable toxicity in patients with advanced
      biliary tract cancer.

PMID- 20811896
TI  - Chiari 1 malformation and holocord syringomyelia presenting as abrupt onset foot
      drop.
AB  - We present two patients with a Chiari 1 malformation and holocord syringomyelia
      who presented with abrupt onset unilateral foot drop. Neurophysiologic testing
      was consistent with a proximal nerve root lesion. This assisted with localization
      and directed magnetic resonance (MR) imaging to lumbosacral spine and nerve
      roots. Each child underwent a suboccipital craniectomy and laminectomy with
      duroplasty to decompress the foramen magnum. Each child also showed rapid and
      complete clinical recovery despite the significant electromyographic and MRI
      abnormalities on initial study.

PMID- 20811897
TI  - Neuroendoscopic fenestration of the foramen of Monro without septostomy for
      unilateral hydrocephalus following neonatal intraventricular hemorrhage.
AB  - PURPOSE: Unilateral hydrocephalus is a rare type of hydrocephalus caused by
      germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) in preterm
      infants. We present a case of posthemorrhagic unilateral hydrocephalus in a
      preterm infant that was successfully treated with neuroendoscopic fenestration of
      the foramen of Monro without septostomy. CASE REPORT: Brain ultrasound of a
      female infant born at 26(+1) weeks gestation revealed delayed unilateral
      hydrocephalus in the frontal horn of the lateral ventricle after IVH. In this
      case, unilateral hydrocephalus appeared to be caused by chronic inflammatory
      changes, leading to membrane formation in the foramen of Monro. After
      neuroendoscopic foraminoplasty without septostomy, ventricular size decreased,
      and the patient's neurological status improved per the PREMIE-NEURO exam, a
      neurologic examination for preterm infants of gestational age 23-37 weeks.
      CONCLUSIONS: This case demonstrates that simple repermeation of the foramen
      without fenestration of the septum pellucidum can successfully treat membrane
      induced unilateral hydrocephalus. Also, because hydrocephalus can develop even
      after stabilization of GMH-IVH, close follow-up during the first year of life and
      beyond may reduce the likelihood of brain damage due to advanced hydrocephalus.

PMID- 20811898
TI  - Influence of acute and chronic myocardial loading conditions, function,
      structural changes and extracardiac factors on NT-proBNP in asymptomatic patients
      with preserved ejection fraction.
AB  - BACKGROUND: We compared the effect of different loading conditions, parameters of
      structural heart disease and extracardiac confounders on NT-proBNP to validate
      the application of NT-proBNP for a characterisation of loading conditions and
      clinical course of patients with chronic heart diseases. METHODS: NT-proBNP was
      measured in 15 controls and 34 patients with preserved ejection fraction and
      chronic pressure (by aortic stenosis) or volume overload (by aortic or mitral
      regurgitation) before and after physical as well as dobutamine stress. Myocardial
      fibrosis was evaluated by contrast-enhanced cardiovascular magnetic resonance.
      RESULTS: In patients with elevated NT-proBNP due to chronic pressure or volume
      overloaded ventricles, physical and dobutamine stress were associated with only
      marginal nonsignificant additional NT-proBNP responses. Univariate analyses
      showed that myocardial fibrosis has the greatest effect on NT-proBNP (P < 0.01).
      Forward regression analyses revealed left ventricular filling, systolic function,
      the presence of valvular heart disease, serum creatinine and responses to
      dobutamine stress as independent determinants of NT-proBNP (P < 0.05 each).
      CONCLUSION: NT-proBNP cannot be used simply to characterise intensity of
      ventricular load. Character and duration of loading conditions, cardiac structure
      and function, as well as confounders should be considered when NT-proBNP is used
      for clinical follow-up assessment.

PMID- 20811899
TI  - Predictive value of middle cerebral artery to uterine artery pulsatility index
      ratio in preeclampsia.
AB  - OBJECTIVE: To determine the predictive value of middle cerebral artery (MCA) to
      uterine artery pulsatility index (PI) ratio in preeclamptic patients. METHODS:
      This prospective cross-sectional study was performed on 64 preeclamptic and 131
      normal pregnancies at or beyond 26 weeks of gestation between June 2007-August
      2008 in the high-risk pregnancy unit of Dr. Zekai Tahir Burak Women Health
      Teaching and Research Hospital, Ankara. Doppler blood flow velocimetry of the
      uterine and umbilical arteries and fetal MCA was measured. The ratios between the
      PI of MCA and the mean PI value of both uterine arteries were calculated and
      values below the fifth percentile were considered as brain-sparing. The ratios
      between the PI of MCA and PI of the umbilical artery were calculated and values
      lower than 1.08 were considered as brain-sparing and the results were related to
      perinatal outcome. Statistical analysis were performed using the SPSS Software
      (SPSS, Chicago, IL, USA) version 9.0 for Windows. Odds ratio with 95% confidence
      interval (95%) was also used for statistical analysis. RESULTS: In 11 (42.3%) of
      the preeclamptic pregnancies that had abnormal MCA/uterine artery PI, 4 of them
      had severe preeclampsia and 7 had mild preeclampsia. In the low MCA/uterine
      artery PI ratio group, a statistically significantly higher rate of Cesarean
      section (66 vs. 88.46%), NICU admission (26.3 vs. 57.6%), preterm birth (52.6 vs.
      92.3%) was found. Abnormal MCA/uterine artery PI ratio and abnormal MCA/umbilical
      artery PI ratio in the prediction of adverse outcome of pregnancy was compared.
      In the prediction of preterm birth, which was better for the MCA/uterine artery,
      there was a significant difference between the ratios (P = 0.005). CONCLUSION:
      Our results suggest that MCA/uterine artery PI ratio is a good predictor of
      neonatal outcome in preeclamptic patients in the third trimester and could be
      used to identify fetuses at risk of morbidity and mortality.

PMID- 20811900
TI  - Craniosynostosis: prenatal diagnosis by means of ultrasound and SSSE-MRI. Family
      series with report of neurodevelopmental outcome and review of the literature.
AB  - INTRODUCTION: Craniosynostosis is a condition characterized by a premature
      closure of one or more skull sutures and refers to a wide spectrum of cranial
      malformation with an estimated birth of 1:2,000-1:4,000 live births. Four
      receptors (FGFR 1, FGFR 2, FGFR 3, FGFR 4) involving mutation in the fibroblast
      growth factor have been identified. MATERIALS AND METHODS: Two cases occurred in
      the same family and diagnosed prenatally by means of ultrasound, and antenatal
      and postnatal MR imaging are reported. Molecular biology regarding identification
      of craniosynostosis type has been analyzed. A revision of the medical literature
      is also provided. CONCLUSION: The premature closure of sagittal suture is
      characterized by a disproportionately large occipito-frontal and short biparietal
      diameter (scaphocephaly). The prenatal ultrasound diagnosis of craniosynostosis
      in utero may be difficult and be suspected when the cephalic index, the cranial
      shape or the fetal face shape are abnormal. Fetal karyotype is recommended and
      DNA testing plays a critical role in achieving an appropriate diagnosis, when
      possible. The prognosis of craniosynostosis is primarily dependent on the
      presence of associated anomalies as craniosynostosis are correlated with three to
      fivefold increased risk for cognitive disabilities.

PMID- 20811901
TI  - Drug-induced sleep endoscopy: conventional versus target controlled infusion
      techniques--a randomized controlled study.
AB  - Understanding the sites of pharyngeal collapse is mandatory for surgical
      treatment decision-making in obstructive sleep-apnea-hypopnea syndrome patients.
      Drug-induced sleep endoscopy (DISE) allows for the direct observation of the
      upper airway during sedative-induced sleep. In order to re-create snoring and
      apnea patterns related to a spontaneous sleep situation, the authors used a
      target-controlled infusion (TCI) sleep endoscopy (DISE-TCI), comparing this
      technique to conventional DISE, in which sedation was reached by a manual bolus
      injection. The authors conducted a prospective, randomized, unicenter study. The
      apneic event observation and its correlation with pharyngeal collapse patterns is
      the primary endpoint; secondary endpoints are defined as stability and safety of
      sedation plans of DISE-TCI technique. From January 2009 to June 2009, 40 OSAHS
      patients were included in the study and randomized allocated in two groups: the
      bolus injection conventional DISE group and the DISE-TCI group. We recorded the
      complete apnea event at the oropharynx and hypopharynx levels in 4 patients of
      the conventional DISE group (20%) and in 17 patients of the DISE-TCI group (85%)
      (P < 0.0001). Two patients needed oxygen in the conventional DISE group because
      of severe desaturation that resulted from the first bolus of propofol (1 mg/kg)
      (P = 0.4872 ns). We recorded the instability of the sedation plan in 13 patients
      from the conventional DISE group (65%) and 1 patient from the DISE-TCI group (5%)
      (P = 0.0001). Our results suggest that the DISE-TCI technique should be the first
      choice in performing sleep endoscopy because of its increased accuracy, stability
      and safety.

PMID- 20811902
TI  - Expression of pro-inflammatory TACE-TNF-alpha-amphiregulin axis in Sjogren's
      syndrome salivary glands.
AB  - The tumor-necrosis-factor-converting-enzyme (TACE)-TNF-alpha-Amphiregulin (AREG)
      axis plays an important pathogenic role in inflammatory and autoimmune disorders.
      However, the pathological roles of these proteins in the chronic autoimmune
      disease Sjogren's syndrome (SS) remain to be elucidated. It is known that the
      TACE-AREG axis is clearly part of a larger cascade of signals that starts with
      the activation of Furin, responsible for maturation of TACE that, in turn,
      determines the production of active TNF-alpha, directly involved in the up
      regulation of AREG expression. This study showed that Furin, TACE, TNF-alpha, and
      AREG proteins, detected in acinar and ductal cells of human salivary glands from
      SS patients, increased remarkably in comparison with biopsies of labial salivary
      glands from healthy controls. The changes in Furin, TACE, TNF- alpha, and AREG
      proteins' level detected in salivary glands biopsies of SS patients could be
      responsible for pro-inflammatory cytokines overexpression characterizing
      Sjogren's syndrome.

PMID- 20811903
TI  - Wilms' tumour protein Wt1 stimulates transcription of the gene encoding vascular
      endothelial cadherin.
AB  - The Wilms' tumour gene, Wt1, encodes a zinc finger protein, which is mutated in a
      subset of paediatric renal carcinomas known as Wilms' tumours (nephroblastomas).
      Recent findings indicate that Wt1, beside its role in genitourinary development,
      is also necessary for normal vascularisation of the embryonic heart, and may even
      be involved in tumour angiogenesis. The original purpose of this study was to
      decipher potential downstream signalling pathways of Wt1 for blood vessel
      formation. We found that the Wt1(-KTS) protein, which functions as a
      transcription factor, stimulated the expression of cadherin 5 (CDH5, vascular
      endothelial (VE) cadherin) and other vascular genes, i.e. those encoding vascular
      endothelial growth factor receptors 1 and 2, and angiopoietin-2. Furthermore, an
      enhancer element was identified in the first intron of the CDH5 gene, which bound
      to the Wt1(-KTS) protein and was necessary for reporter gene activation by Wt1(
      KTS) in transiently transfected cell lines. Wt1 and VE-cadherin proteins could be
      co-localised by double immunofluorescence staining in maturating glomeruli of
      embryonic murine kidneys. VE-cadherin transcripts were reduced in some but not
      all tissues of Wt1-deficient mouse embryos. These results indicate that Wt1 can
      stimulate vascular gene transcription. By demonstrating that Wt1(-KTS) protein
      trans-activates an enhancer element in the first intron we identified CDH5 as a
      novel target gene of Wt1. It is suggested that transcriptional activation of CDH5
      by Wt1 fulfils regulatory functions during vascular development and kidney
      formation.

PMID- 20811904
TI  - Control of neurotransmitter release: From Ca2+ to voltage dependent G-protein
      coupled receptors.
AB  - This review discusses two theories that try to explain mechanisms of control of
      neurotransmitter release in fast synapses: the Ca(2+) hypothesis and the Ca(2+)
      voltage hypothesis. The review summarizes experimental results that are
      incompatible with predictions from the Ca(2+) hypothesis and concludes that
      Ca(2+) is involved in the control of the amount of release but not in the control
      of the time course of evoked release, i.e., initiation and termination of evoked
      release. Results summarizing direct effects of changes in membrane potential on
      the release machinery are then presented. These changes in membrane potential
      affect the affinity (for the transmitter) of presynaptic autoinhibitory G-protein
      coupled receptors (GPCRs). The voltage dependence of these GPCRs and their
      pivotal role in determining the time course of evoked release is discussed.

PMID- 20811905
TI  - RLK7, a leucine-rich repeat receptor-like kinase, is required for proper
      germination speed and tolerance to oxidative stress in Arabidopsis thaliana.
AB  - The leucine-rich repeat class of receptor-like kinase (LRR-RLKs) encoding genes
      represents the largest family of putative receptor genes in the Arabidopsis
      thaliana genome. However, very little is known about the range of biological
      process that they control. We present in this paper the functional
      characterization of RLK7 that has all the structural features of a receptor-like
      kinase of the plant-specific LRR type. To this end, we identified and
      characterized three independent T-DNA insertion mutants, constructed lines
      carrying truncated versions of this putative receptor, one lacking the
      cytoplasmic kinase domain (RLK7Deltakin) and the other one lacking 14 LRR repeats
      (RLK7DeltaLRR) and generated RLK7 overexpressing lines. We thus provide evidences
      that RLK7 is involved in the control of germination speed and the tolerance to
      oxidant stress. First, consistent with the expression kinetics of the RLK7 gene
      in the seeds, we found that all three mutants showed a delay in germination,
      whereas the overexpressors, RLK7Deltakin and RLK7DeltaLRR lines displayed a
      phenotype of more precocious germination. Second, a non-hypothesis driven
      proteomic approach revealed that in the seedlings of the three T-DNA insertion
      lines, four enzymes directly or indirectly involved in reactive oxygen species
      detoxification, were significantly less abundant. Consistent with this finding,
      the three mutants were less tolerant than the wild type to a hydrogen peroxide
      treatment, whereas the overexpressors, RLK7Deltakin and RLK7DeltaLRR lines
      presented the opposite phenotype.

PMID- 20811906
TI  - Expression and functional analysis of two genes encoding transcription factors,
      VpWRKY1 and VpWRKY2, isolated from Chinese wild Vitis pseudoreticulata.
AB  - In this study, two WRKY genes were isolated from Erysiphe necator-resistant
      Chinese wild Vitis pseudoreticulata W. T. Wang 'Baihe-35-1', and designated as
      VpWRKY1 (GenBank accession no. GQ884198) and VpWRKY2 (GenBank accession no.
      GU565706). Nuclear localization of the two proteins was demonstrated in onion
      epidermal cells, while trans-activation function was confirmed in the leaves of
      'Baihe-35-1'. Expression of VpWRKY1 and VpWRKY2 was induced rapidly by salicylic
      acid treatment in 'Baihe-35-1'. Expression of VpWRKY1 and VpWRKY2 was also
      induced rapidly by E. necator infection in 11 grapevine genotypes; the maximum
      induction of VpWRKY1 was greater in E. necator-resistant grapevine genotypes than
      in susceptible ones post E. necator inoculation. Furthermore, ectopic expression
      of VpWRKY1 or VpWRKY2 in Arabidopsis enhanced resistance to powdery mildew
      Erysiphe cichoracearum, and enhanced salt tolerance of transgenic plants. VpWRKY2
      also enhanced cold tolerance of transgenic plants. In addition, the two proteins
      were shown to regulate the expression of some defense marker genes in Arabidopsis
      and grapevine. The data suggest that VpWRKY1 and VpWRKY2 may underlie the
      resistance in transgenic grapevine to E. necator and tolerance to salt and cold
      stresses.

PMID- 20811907
TI  - Diagnosis of alpha-1-antitrypsin deficiency in bleeding disorder-related neonatal
      death.
AB  - Alpha-1-antitrypsin (AAT) deficiency is a rare genetic disorder characterized by
      hepatitis in neonates, childhood and adulthood (protease inhibitor (PI)*ZZ) and
      emphysema with or without hepatitis (PI*ZZ)/(PI*SS,SZ or null) in adulthood. We
      report the case of a female neonate born at 40 weeks of gestation who presented
      with vitamin K deficiency-related intracranial bleeding and cholestasis of which
      she died at 28 days of age. At autopsy, the infant was found to have intracranial
      bleeding, hepatomegaly, and cholestasis with paucity of bile ducts in the liver.
      Small periodic acid-Schiff diastase positive intrahepatic granules and positive
      staining with antibodies against AAT protein suggested an AAT deficiency. AAT is
      a glycoprotein that has a protease inhibitor function. Its deficiency can be the
      result of various point mutations in Serpin 1 located on chromosome 14. The
      diagnosis AAT deficiency was confirmed by mutation analysis showing the PI*ZZ
      genotype in the neonate. In conclusion, AAT deficiency is a rare genetic disorder
      that can lead to a serious bleeding disorder in the neonatal period if not
      recognised on time. Pathological diagnosis together with verifying molecular
      analysis can be used to identify index patients.

PMID- 20811908
TI  - Assessment of pediatric asthma drug use in three European countries; a TEDDY
      study.
AB  - Asthma drugs are amongst the most frequently used drugs in childhood, but
      international comparisons on type and indication of use are lacking. The aim of
      this study was to describe asthma drug use in children with and without asthma in
      the Netherlands (NL), Italy (IT), and the United Kingdom (UK). We conducted a
      retrospective analysis of outpatient medical records of children 0-18 years from
      1 January 2000 until 31 December 2005. For all children, prescription rates of
      asthma drugs were studied by country, age, asthma diagnosis, and off-label
      status. One-year prevalence rates were calculated per 100 children per patient
      year (PY). The cohort consisted of 671,831 children of whom 49,442 had been
      diagnosed with asthma at any time during follow-up. beta2-mimetics and inhaled
      steroids were the most frequently prescribed asthma drug classes in NL (4.9 and
      4.1/100 PY), the UK (8.7 and 5.3/100 PY) and IT (7.2 and 16.2/100 PY),
      respectively. Xanthines, anticholinergics, leukotriene receptor antagonists, and
      anti-allergics were prescribed in less than one child per 100 per year. In
      patients without asthma, beta2-mimetics were used most frequently. Country
      differences were highest for steroids, (Italy highest), and for beta2-mimetics
      (the UK highest). Off-label use was low, and most pronounced for beta2-mimetics
      in children <18 months (IT) and combined beta2-mimetics + anticholinergics in
      children <6 years (NL). CONCLUSION: This study shows that among all asthma drugs,
      beta2-mimetics and inhaled steroids are most often used, also in children without
      asthma, and with large variability between countries. Linking multi-country
      databases allows us to study country specific pediatric drug use in a systematic
      manner without being hampered by methodological differences. This study
      underlines the potency of healthcare databases in rapidly providing data on
      pediatric drug use and possibly safety.

PMID- 20811909
TI  - Long-term balancing selection maintains trans-specific polymorphisms in the human
      TRIM5 gene.
AB  - The human TRIM5 genes encodes a retroviral restriction factor (TRIM5alpha).
      Evolutionary analyses of this gene in mammals have revealed a complex and
      multifaceted scenario, suggesting that TRIM5 has been the target of exceptionally
      strong selective pressures, possibly exerted by recurrent waves of retroviral
      infections. TRIM5 displays inter-individual expression variability in humans and
      high levels of TRIM5 mRNA have been associated with a reduced risk of HIV-1
      infection. We resequenced TRIM5 in chimpanzees and identified two polymorphisms
      in intron 1 that are shared with humans. Analysis of the gene region encompassing
      the two trans-specific variants in human populations identified exceptional
      nucleotide diversity levels and an excess of polymorphism compared to fixed
      divergence. Most tests rejected the null hypothesis of neutral evolution for this
      region and haplotype analysis revealed the presence of two deeply separated
      clades. Calculation of the time to the most recent common ancestor (TMRCA) for
      TRIM5 haplotypes yielded estimates ranging between 4 and 7 million years.
      Overall, these data indicate that long-term balancing selection, an extremely
      rare process outside MHC genes, has maintained trans-specific polymorphisms in
      the first intron of TRIM5. Bioinformatic analyses indicated that variants in
      intron 1 may affect transcription factor-binding sites and, therefore, TRIM5
      transcriptional activity. Data herein confirm an extremely complex evolutionary
      history of TRIM5 genes in primates and open the possibility that regulatory
      variants in the gene modulate the susceptibility to HIV-1.

PMID- 20811910
TI  - FTO influences on longitudinal BMI over childhood and adulthood and modulation on
      relationship between birth weight and longitudinal BMI.
AB  - SNP rs9939609 within the fat mass and obesity associated gene (FTO) is strongly
      associated with adult body mass index (BMI). However, influences of FTO on
      longitudinal BMI change from childhood to adulthood have not been examined.
      Knowledge is limited on FTO, modulating the association between birth weight and
      longitudinal change of BMI. This longitudinal study examined SNPs of FTO in 658
      white subjects from childhood (3-17 years) to adulthood (18-45 years). No
      significant associations of FTO SNPs with either birth weight or longitudinal BMI
      over childhood were noted after multiple-test adjustment. However, three SNPs
      (rs9939609, rs17820875 and rs860713) with different inheritance patterns were
      identified to be associated with longitudinal BMI over adulthood after Bonferroni
      adjustment (P = 5.3 * 10(-5), 2.0 * 10(-4) and 0.001). In addition, interactions
      were discovered between birth weight and SNPs of rs17820875 (P = 0.001) and
      rs860713 (0.002). A negative association between birth weight and adult BMI were
      found in risk genotype AG of rs17820875 and GG of rs860713 in contrast to
      positive associations in other genotypes. These findings led to the conclusion
      that lower birth weight predisposes to higher adult BMI depending on FTO risk
      genotypes. Our studies underscore the importance of FTO influences on obesity and
      provide insights into the evolution of the long-term burden of obesity.

PMID- 20811911
TI  - Fire as a selective force in a Bornean tropical everwet forest.
AB  - Tree species rarely exposed to burning, like in everwet tropical forests, are
      unlikely to be fire adapted. Therefore, one could hypothesize that these species
      are affected equally by burning and that tree abundance changes are linked solely
      to fire behavior. Alternatively, if species do react differentially to burning,
      abundance changes should be linked to tree habitat preference and morphology.
      Using tree inventories from old-growth and adjacent burned Bornean forest in
      combination with a database on tree morphology and habitat preference, we test
      these alternative hypotheses by (1) determining whether species specific
      abundance changes after fire differ significantly from equal change, and (2)
      whether observed abundance changes are linked to species morphology and habitat
      preference. We found that of 196 species tested, 125 species showed an abundance
      change significantly different from that expected under our null model of equal
      change. These abundance changes were significantly linked to both tree morphology
      and habitat preference. Abundance declines were associated with slope or ridge
      preference, thin barks, and limited seed dormancy. Abundance increases were
      associated with high light preference, small adult stature, light wood, large
      leaves, small seeds and long seed dormancy. While species habitat preference and
      morphology explained observed abundance increases well, abundance declines were
      only weakly associated with them (R(2) ~ 0.09). This suggests that most tree
      mortality was random and everwet tropical tree species are poorly fire adapted.
      As fire frequencies are increasing in the everwet tropics, this might eventually
      result in permanently altered species compositions and even species extinctions.

PMID- 20811912
TI  - Indeterminate laying and flexible clutch size in a capital breeder, the common
      eider.
AB  - Clutch size control in capital breeders such as large waterfowl has been much
      debated. Some studies have concluded that clutch size in ducks is determined
      before the start of laying and does not change in response to egg additions or
      removals. The response, however, may depend on the timing of tests, and
      experiments may have been too late for females to alter the number of eggs. We
      here study clutch size responses to predation of first and second eggs in the
      common eider, using protein fingerprinting of egg albumen to verify that the same
      female continues laying in the nest after predation. Sixty of 79 females with
      early egg predation (one or both of the two first eggs) deserted the nest. Among
      the 19 females that stayed and continued laying, the mean number of eggs produced
      was 4.4, significantly higher than the 3.7 in non-predated nests. The staying
      females had similar egg size and clutch initiation date as females that deserted,
      and their body mass and clutch initiation date was similar to that of females
      whose clutches were not predated. Even capital-breeding common eiders may
      therefore be indeterminate layers, as many females in which early eggs are
      removed lay more eggs than others. A previous study has shown that they can
      reduce their laying if eggs are added. Our results add to increasing evidence
      that ducks have more flexible egg production than previously thought.

PMID- 20811913
TI  - First evidences of sexual selection by mate choice in marine zooplankton.
AB  - Sexual selection is potentially important in marine zooplankton, presumably the
      most abundant metazoans on earth, but it has never been documented. We examine
      the conditions for sexual selection through mate choice and describe mating
      preferences in relation to size in a marine zooplankter, the pelagic copepod
      Acartia tonsa. Males produce spermatophores at a rate (~1 day(-1)) much lower
      than known female encounter rates for most of the year and the decision to mate a
      particular female thus implies lost future opportunities. Female egg production
      increases with female size, and males mating larger females therefore sire more
      offspring per mating event. Similarly, females encounter males more frequently
      than they need to mate. Large males produce larger spermatophores than small
      males and the offspring production of female increases with the size of the
      spermatophore she receives. Additionally, large spermatophores allow females to
      fertilize eggs for a longer period. Thus, mating with large males reduces the
      female's need for frequent matings and she may sire sons that produce more
      offspring because size is heritable in copepods. Finally, we show that both males
      and females mate preferentially with large partners. This is the first
      demonstration of sexual selection by mate choice in a planktonic organism.

PMID- 20811914
TI  - Risk factors at pretreatment predicting treatment-induced nausea and vomiting in
      Australian cancer patients: a prospective, longitudinal, observational study.
AB  - PURPOSE: Despite significant advances in antiemetic management, almost 50% of
      cancer patients still experience nausea and vomiting during treatment. The goal
      of antiemetic therapy is complete prevention of treatment-induced nausea and/or
      vomiting (TINV); however, realisation of this goal remains elusive, thus
      supplementary strategies identifying patients at high risk must be employed in
      the interim. Consequently, we examined TINV incidence and its risk factors,
      including patient, clinical and pretreatment quality of life (QOL)/psychological
      factors. METHODS: Two hundred newly diagnosed cancer patients beginning combined
      treatment participated in this prospective, longitudinal, observational study.
      QOL (including TINV), psychological adjustment, and patient/clinical
      characteristics were examined at pretreatment, on-treatment (8 weeks +/- 1 week)
      and post-treatment. RESULTS: Overall, 62% of patients experienced TINV, with TIN
      incidence (60%) doubling that of TIV (27%). Eight independent risk factors
      predicted 73% of TIN incidence: high premorbid/anticipatory NV, moderately/highly
      emetogenic chemotherapy (M/HEC), longer treatment (>3 months), female gender,
      surgery prior to adjuvant chemotherapy +/- radiotherapy, private health insurance
      and low emotional functioning (pretreatment). Six independent risk factors
      predicted 77% of TIV incidence: premorbid/anticipatory vomiting, M/HEC, female
      gender, cancer resection and low role functioning (pretreatment). CONCLUSIONS:
      TINV still represents a very major concern for patients. Several pretreatment
      risk factors for the development of TIN and TIV, respectively, were identified.
      Patients about to undergo cancer treatment, particularly combined treatment
      involving emetogenic chemotherapy and surgery, should be screened for these
      factors with a view to modifying standard pretreatment/maintenance antiemetic
      therapy. Furthermore, and consistent with recent research, it is recommended that
      more comprehensive interventions combining antiemetics with other effective
      pharmacological (e.g. anxiolytics) and non-pharmacological approaches (e.g.
      acupuncture, relaxation techniques) be considered by clinicians in attempts to
      improve control of TIN and TIV (and overall QOL) for their patients. In this way,
      optimal holistic care will be ensured for cancer patients by clinicians providing
      conventional oncology treatment.

PMID- 20811915
TI  - Robot-assisted laparoscopic pancreaticoduodenectomy.
AB  - BACKGROUND: Robotic surgery is the most advanced development in minimally
      invasive surgery. However, the number of reports on robot-assisted endoscopic
      gastrointestinal surgery is still very small. In this article, we describe total
      laparoscopic pancreaticoduodenectomy (PD) undertaken using the da Vinci Surgical
      System(r) (Intutive Surgical). METHODS: Three patients underwent robotic PD
      between November 2009 and February 2010. Following resection of the pancreatic
      head, duodenum, and the distal stomach, intracorporeal anastomosis was
      accomplished by Child's method of reconstruction, which includes a two-layered
      end-to-side pancreaticojejunostomy, an end-to-side choledochojejunostomy, and a
      side-to-side gastrojejunostomy. RESULTS: The time required for surgery was 703 +/
      141 min, and blood loss was 118 +/- 72 mL. The average hospital stay period was
      26 +/- 12 days. As a postoperative complication, pancreatic juice leak occurred
      in one case, but it was managed with conservative treatment. Of the three
      patients, one had cancer of the papilla of Vater, one had cancer of the
      pancreatic head, and one had a solid pseudopapillary neoplasm. In all cases, the
      surgical margin was negative for tumor. CONCLUSIONS: Robot-assisted PD required a
      long time, but organ removal with less bleeding was able to be safely performed
      owing to the high degree of freedom associated with the forceps manipulation and
      the magnified view. Similarly, pancreatojejunostomy could certainly be conducted.
      No major postoperative complications were found. Accumulation of da Vinci PD
      experience in the future will lead to safer and faster PD.

PMID- 20811916
TI  - Autoimmune pancreatitis mimicking pancreatic cancer.
AB  - BACKGROUND/PURPOSE: Autoimmune pancreatitis (AIP) is a form of chronic
      pancreatitis that can often be difficult to distinguish from pancreatic cancer.
      We describe the clinical and radiographic features of 23 patients with AIP whose
      presentations mimicked pancreatic cancer. METHODS: A review of clinic, radiology,
      and endoscopy records from a 6-year period identified patients with AIP initially
      suspected of having pancreatic cancer. Abdominal computed tomography (CT) with
      intravenous contrast, endoscopic ultrasonography (EUS), and/or ERCP was performed
      in each patient. The diagnosis of AIP was made histologically and/or
      cytologically for each patient. RESULTS: Nineteen of 23 patients (83%) presented
      with new-onset weight loss, jaundice, or both. Nineteen (83%) patients had CT
      findings worrisome for pancreatic cancer including: (1) pancreatic enlargement or
      focal mass, (2) regional lymphadenopathy, and/or (3) vascular invasion. Eighteen
      patients (78%) had common bile duct strictures on ERCP. EUS-guided fine-needle
      aspiration biopsies excluded pancreatic cancer in all 22 patients who had EUS
      (96%). Seven patients had surgery for continued suspicion of pancreatic cancer.
      CONCLUSIONS: Although AIP commonly presents with features suggestive of
      pancreatic cancer, clinical recognition of AIP with appropriate diagnostic
      testing including EUS with fine-needle aspiration, ERCP, IgG4 levels, and
      pancreatic protocol CT expedites diagnosis and can spare patients unnecessary
      surgery.

PMID- 20811917
TI  - Comparisons of two different doses of fentanyl for procedural analgesia during
      epidural catheter placement: a double-blind prospective, randomized, placebo
      controlled study.
AB  - The purpose of this study was to investigate the effect of fentanyl on analgesic
      properties and respiratory responses during an epidural procedure. Sixty patients
      premedicated with oral brotizolam 0.25 mg were allocated to receive procedural
      analgesia with saline or 25 or 50 MUg of fentanyl. Five minutes after
      administration, an epidural procedure was started. Pain assessments were made
      immediately after the epidural catheter placement using a visual analog scale.
      The lowest SpO2 levels during the procedure were recorded to evaluate respiratory
      depression, and cardiovascular complications were also recorded. The pain scores
      were significantly lower in the 25 and 50 MUg fentanyl groups than in the placebo
      group (P < 0.01). There was no difference in pain assessment between the 25 and
      50 MUg fentanyl groups. The lowest SpO2 value of the 50 MUg fentanyl group was
      significantly lower than those of the other groups (P < 0.001). Seven of 20 cases
      in the 50 MUg fentanyl group needed oxygen administration because of a decreased
      SpO2 value (<94%). No cardiovascular complications were observed in any group
      during the entire study period. Thus, intravenous fentanyl at a dose of 25 MUg
      provides effective procedural analgesia without the risk of hypoxemia during an
      epidural procedure in a patient with preanesthetic medication.

PMID- 20811918
TI  - Lidocaine spray 10 min prior to intubation: effects on postoperative sore throat.
AB  - A sore throat is the most frequent adverse side effect of general anesthesia. The
      purpose of this study was to compare the different types and timing of lidocaine
      application based on the effectiveness of reducing postoperative sore throat
      (POST) after endotracheal intubation. In group A, 8% lidocaine was sprayed on
      laryngopharyngeal structures immediately before intubation, and the distal ends
      of the endotracheal tubes (ETTs) were lubricated with 2% lidocaine gel. In group
      B, 8% lidocaine was sprayed, and ETTs were lubricated with normal saline. In
      groups C and D, no lidocaine was sprayed, and the ETTs were lubricated with
      normal saline (C, control) or with 2% lidocaine gel (D). In group E, 8% lidocaine
      was sprayed 10 min prior to endotracheal intubation, and the ETTs were lubricated
      with normal saline. In 527 patients, 28.2% reported POST at 24 h following
      extubation. Statistically significant differences in the incidence of POST were
      found only between group E (16.0%) and each of the other groups (28.4-38.5%),
      except for group B (26.5%). In conclusion, 8% lidocaine spray significantly
      reduced the incidence of POST if it was sprayed on laryngopharyngeal structures
      10 min prior to endotracheal intubation.

PMID- 20811919
TI  - Regression of meningiomas after discontinuation of cyproterone acetate in a
      transsexual patient.

PMID- 20811920
TI  - Gastrectomy and chemotherapy with S-1 for gastric cancer in a patient with
      acquired immunodeficiency syndrome.
AB  - Total gastrectomy and chemotherapy with S-1 after surgery were performed in a 50
      year-old woman with gastric cancer associated with acquired immunodeficiency
      syndrome (AIDS). She was given a diagnosis of gastric cancer at the lesser
      curvature of the body of the stomach, and distal gastrectomy was performed in
      December 2004. The postoperative course was eventful, with persistent high fever
      of unknown origin after surgery and infiltrative shadows in the bilateral lung
      fields showing on CT scan. Polymerase chain reaction (PCR) for pneumocystis
      carinii on bronchoscopy was positive, serum HIV antibody was positive, HIV-RNA
      was 2.2 * 10(5) copies/ml, and the serum CD4 lymphocyte level was 25/mm(3) on
      postoperative day 28. She was given a diagnosis of pneumocystis carinii with
      AIDS. Pneumocystis carinii and fever improved immediately when ST mixture and
      highly active antiretroviral therapy (HAART) were performed. After 3 months, the
      serum CD4 lymphocyte level was elevated to 125/mm(3), and she underwent total
      gastrectomy because cancer cells at the cut end of the resected stomach were
      positive microscopically. The postoperative course was uneventful, and she
      underwent adjuvant chemotherapy with S-1 because the serum CD4 lymphocyte level
      was 568/mm(3). S-1 therapy was continued for 2 years (each course consisting of 2
      weeks of administration followed by 2 weeks off) while performing HAART and
      monitoring CD4 lymphocyte levels. No side effects such as decreases in white
      blood cell counts or CD4 lymphocyte levels were seen during S-1 therapy. She is
      alive and well without recurrence of gastric cancer 5 years after initial
      gastrectomy.

PMID- 20811921
TI  - Treatment of early rectal cancer.
AB  - The treatment of rectal cancer has undergone a tremendous surgical evolution over
      the past century. In the past three decades, transanal excision has emerged as a
      popular treatment option for T1 and selected T2 rectal adenocarcinomas, allowing
      less morbidity for early cancers. The surgical options offered to the patient are
      the Parks' per anal excision and the transanal endoscopic microsurgery (TEM).

PMID- 20811922
TI  - Septic versus aseptic hip revision: how different?
AB  - BACKGROUND: The few available studies directly comparing aseptic and septic joint
      revision surgery report conflicting results. We investigated whether two-stage
      revision of septic hip prosthesis with a preformed antibiotic-loaded spacer and
      an uncemented prosthesis provides hip function and quality of life similar to
      those provided by aseptic revision surgery in the medium term, as well as the
      associated direct hospital costs. MATERIALS AND METHODS: We prospectively
      evaluated the hip function (Harris hip score) and quality of life (WOMAC and SF
      12 scores) of 80 patients who underwent one-stage revision for aseptic loosening
      (Group A, 40 patients) or two-stage revision for septic total hip prostheses
      (Group S, 40 patients). Patients were matched for gender, age, and bone loss. A
      preformed antibiotic-loaded cement spacer was used for two-stage revision, and
      uncemented modular prostheses were implanted at revision in both groups. The
      minimum follow-up was 2 years (average 4 years; range 2-6 years). RESULTS: We
      found no difference in infection recurrence or aseptic loosening rate in the two
      groups. Average Harris hip score increased similarly in both groups: from 19.1 to
      74.0 in Group A versus 15.0-71.2 in Group S. Patient-reported quality-of-life
      questionnaires (SF-12 and WOMAC) at last follow-up were similar postoperatively,
      but the complication rate for Group S was twice that of Group A (20.8 versus
      10%). Mean overall hospital-related costs of two-stage procedures were 2.2 times
      greater than those for aseptic revisions. CONCLUSIONS: Two-stage revision for
      infected hip prostheses, using a preformed antibiotic-loaded cement spacer and
      uncemented revision prosthesis, offers a success rate comparable to noninfected
      revisions in the medium term but is associated with a higher complication rate
      and costs.

PMID- 20811923
TI  - Direct comparison of polyethylene wear in cemented and uncemented acetabular
      cups.
AB  - BACKGROUND: It has been indicated that, in the long term, the rate of wear and
      the degree of osteolysis observed with uncemented acetabular components are
      greater than those associated with cemented cups, but most studies which compare
      the wear characteristics of cementless with cemented cups have used historical
      controls. We report a direct comparison of wear of a cemented and an uncemented
      cup with similar design, polyethylene, and sterilization method. MATERIALS AND
      METHODS: The study cohort includes 92 patients who were operated in 1997 with
      primary total hip replacement and have been followed for a period of 9-10 years.
      All patients were operated by posterolateral approach. In patients 70 years or
      older we used a cemented cup, in those 60 years or younger we used an uncemented
      cup, and in patients between 60 and 70 years we used either a cemented or
      uncemented cup as decided by the surgeon. At follow-up, radiographic imaging was
      obtained as standard anterioposterior view of the pelvis, and mean wear was
      determined as described by Livermore et al. RESULTS: The overall wear of the
      cemented acetabular components was 1.07 +/- 0.78 mm, and that of the uncemented
      cups was 1.18 +/- 0.61 mm (P = 0.529). Wear was significantly associated with
      male sex (P = 0.003), younger age (P = 0.003), and degree of inclination (P <
      0.001), but wear was not significantly associated with cemented versus uncemented
      cup (P = 0.437). CONCLUSION: Our findings in this 9-10-year follow-up study
      suggest that cementless cups wear no more than cemented cups of similar design.

PMID- 20811924
TI  - Effect of soya lecithin on the enzymatic system of the white-rot fungi
      Anthracophyllum discolor.
AB  - The present work optimized the initial pH of the medium and the incubation
      temperature for ligninolytic enzymes produced by the white-rot fungus
      Anthracophyllum discolor. Additionally, the effect of soya lecithin on mycelial
      growth and the production of ligninolytic enzymes in static batch cultures were
      evaluated. The critical micelle concentration of soya lecithin was also studied
      by conductivity. The effects of the initial pH (3, 4, and 5) and incubation
      temperature (20, 25, and 30 degrees C) on different enzymatic activities revealed
      that the optimum conditions to maximize ligninolytic activity were 26 degrees C
      and pH 5.5 for laccase and manganese peroxidase (MnP) and 30 degrees C and pH 5.5
      for manganese-independent peroxidase (MiP). Under these culture conditions, the
      maximum enzyme production was 10.16, 484.46, and 112.50 U L(-1) for laccase, MnP,
      and manganese-independent peroxidase MiP, respectively. During the study of the
      effect of soya lecithin on A. discolor, we found that the increase in soya
      lecithin concentration from 0 to 10 g L(-1) caused an increase in mycelial
      growth. On the other hand, in the presence of soya lecithin, A. discolor produced
      mainly MnP, which reached a maximum concentration of 30.64 +/- 4.61 U L(-1) after
      25 days of incubation with 1 g L(-1) of the surfactant. The other enzymes were
      produced but to a lesser extent. The enzymatic activity of A. discolor was
      decreased when Tween 80 was used as a surfactant. The critical micelle
      concentration of soya lecithin calculated in our study was 0.61 g L(-1).

PMID- 20811925
TI  - Analysis of the effect of inoculum characteristics on the first stages of a
      growing yeast population in beer fermentations by means of an individual-based
      model.
AB  - The yeast Saccharomyces cerevisiae has a limited replicative lifespan. The cell
      mass at division is partitioned unequally between a larger, old parent cell and a
      smaller, new daughter cell. Industrial beer fermentations maintain and reuse
      yeast. At the end of fermentation a portion of the yeast is 'cropped' from the
      vessel for 'serial repitching'. Harvesting yeast may select a population with an
      imbalance of young and aged individuals, but the output of any bioprocess is
      dependent on the physiology of each single cell in the population. Unlike
      continuous models, individual-based modelling is an approach that considers each
      microbe as an individual, a unique and discrete entity, with characteristics that
      change throughout its life. The aim of this contribution is to explore, by means
      of individual-based simulations, the effects of inoculum size and cell
      genealogical age on the dynamics of virtual yeast fermentation, focussing on: (1)
      the first stages of population growth, (2) the mean biomass evolution of the
      population, (3) the rate of glucose uptake and ethanol production, and (4) the
      biomass and genealogical age distributions. The ultimate goal is to integrate
      these results in order to make progress in the understanding of the composition
      of yeast populations and their temporal evolution in beer fermentations.
      Simulation results show that there is a clear influence of these initial features
      of the inocula on the subsequent growth dynamics. By contrasting both the
      individual and global properties of yeast cells and populations, we gain insight
      into the interrelation between these two types of data, which helps us to deal
      with the macroscopic behaviour observed in experimental research.

PMID- 20811926
TI  - Role of planktonic and sessile extracellular metabolic byproducts on Pseudomonas
      aeruginosa and Escherichia coli intra and interspecies relationships.
AB  - Bacterial species are found primarily as residents of complex surface-associated
      communities, known as biofilms. Although these structures prevail in nature,
      bacteria still exist in planktonic lifestyle and differ from those in morphology,
      physiology, and metabolism. This study aimed to investigate the influence of
      physiological states of Pseudomonas aeruginosa and Escherichia coli in cell-to
      cell interactions. Filtered supernatants obtained under planktonic and biofilm
      cultures of each single species were supplemented with tryptic soy broth (TSB)
      and used as the growth media (conditioned media) to planktonic and sessile growth
      of both single- and two-species cultures. Planktonic bacterial growth was
      examined through OD(640) measurement. One-day-old biofilms were evaluated in
      terms of biofilm biomass (CV), respiratory activity (XTT), and CFU number.
      Conditioned media obtained either in biofilm or in planktonic mode of life
      triggered a synergistic effect on planktonic growth, mainly for E. coli single
      cultures growing in P. aeruginosa supernatants. Biofilms grown in the presence of
      P. aeruginosa biofilms-derived metabolites presented less mass and activity.
      These events highlight that, when developed in biofilm, P. aeruginosa release
      signals or metabolites able to prejudice single and binary biofilm growth of
      others species and of their own species. However, products released by their
      planktonic counterparts did not impair biofilm growth or activity. E. coli,
      living as planktonic or sessile cultures, released signals and metabolites or
      removed un-beneficial compounds which promoted the growth and activity of all the
      species. Our findings revealed that inter and intraspecies behaviors depend on
      the involved bacteria and their adopted mode of life.

PMID- 20811927
TI  - Clinical significance of thallium-201 SPECT after postoperative radiotherapy in
      patients with glioblastoma multiforme.
AB  - To assess the clinical significance of 201Tl-SPECT after postoperative
      radiotherapy in patients with glioblastoma multiforme (GM). Eighteen patients
      with macroscopically residual GM who underwent 201Tl-SPECT just after
      postoperative radiotherapy were analyzed. Fifteen patients (83%) received
      radiotherapy with a total dose of 60 Gy in conventional fractionation, and the
      remaining three patients were treated with 72 Gy with hyperfractionation
      schedules. Sixteen patients (89%) were treated with chemotherapy that consisted
      of procarbazine, nimustine (ACNU) and vincristine. Concerning 201Tl-SPECT, we
      calculated the radioactivity ratio of the tumors to contralateral normal brain
      (T/N ratio) on early and delayed images after 111 MBq 201Tl chloride injections.
      The median follow-up of all 18 patients was 14.7 months (range, 2.7-38.0 months).
      At the time of this analysis, 15 patients (83%) had died, and the 1-year overall
      survival and the median survival time were 67% and 16.2 months, respectively.
      Fifteen patients (83%) had disease recurrence, and the 1-year progression-free
      survival (PFS) rate and the median time to progression in all 18 patients were
      29% and 7.6 months, respectively. Patients with a high early T/N ratio had a
      significantly poorer PFS than those with a low T/N ratio (P = 0.0131). On
      univariate analysis, early T/N ratio alone had a significant impact on PFS, and
      on mutivariate analysis, early T/N ratio alone was a significant prognostic
      factor for PFS. 201Tl-SPECT after postoperative radiotherapy was predictive of
      PFS in patients with macroscopically residual GM.

PMID- 20811928
TI  - Feasibility study of 21-day-on/7-day-off temozolomide in children with brain
      tumors.
AB  - Temozolomide (TMZ) is an oral alkylating agent with proven antitumoral activity
      in preclinical and clinical studies in adults with high-grade glioma (HGG).
      However, only limited efficacy has been reported in children with HGG using the 5
      day schedule. This study investigated the safety of administering TMZ to children
      and adolescents with brain tumors over an extended period. Extended schedules
      have been proven to overcome chemoresistance without any major toxicity. The
      toxicity of TMZ, administered at 70 mg/m(2)/day orally for 21 consecutive days
      every 28 days, was assessed in children with brain tumors. A total of 156 courses
      of TMZ were given to 17 patients (median age 12.5 years, range 1-17 years), who
      were recruited into the study. Eleven patients had progressive or relapsing
      disease, and six patients were newly diagnosed. In this cohort no cases of toxic
      death or nonhematological toxicity were reported. In comparison with the 5-day
      schedule, thrombocytopenia and neutropenia were noted to be less frequent. Grades
      3 and 4 lymphopenia occurred in 10.8 and 22.4% of courses, respectively; among
      the lymphopenic patients there was one case of disseminated zoster
      (meningoencephalitis and cutaneous involvement), one case of rotavirus
      gastroenteritis, and two cases of herpetic stomatitis reported. The objective
      response rate was 11.8%. Overall, 82.3% of patients showed stable disease. The
      prolonged TMZ schedule appeared to be well tolerated, with few cases of
      neutropenia or thrombocytopenia recorded. Nevertheless, prolonged exposure to TMZ
      was associated with lymphopenia and may lead to a higher rate of viral
      infections.

PMID- 20811930
TI  - Structural interpretation in composite systems using powder X-ray diffraction:
      applications of error propagation to the pair distribution function.
AB  - PURPOSE: To develop a method for drawing statistical inferences from differences
      between multiple experimental pair distribution function (PDF) transforms of
      powder X-ray diffraction (PXRD) data. METHODS: The appropriate treatment of
      initial PXRD error estimates using traditional error propagation algorithms was
      tested using Monte Carlo simulations on amorphous ketoconazole. An amorphous
      felodipine:polyvinyl pyrrolidone:vinyl acetate (PVPva) physical mixture was
      prepared to define an error threshold. Co-solidified products of felodipine:PVPva
      and terfenadine:PVPva were prepared using a melt-quench method and subsequently
      analyzed using PXRD and PDF. Differential scanning calorimetry (DSC) was used as
      an additional characterization method. RESULTS: The appropriate manipulation of
      initial PXRD error estimates through the PDF transform were confirmed using the
      Monte Carlo simulations for amorphous ketoconazole. The felodipine:PVPva physical
      mixture PDF analysis determined +/-3sigma to be an appropriate error threshold.
      Using the PDF and error propagation principles, the felodipine:PVPva co
      solidified product was determined to be completely miscible, and the
      terfenadine:PVPva co-solidified product, although having appearances of an
      amorphous molecular solid dispersion by DSC, was determined to be phase
      separated. CONCLUSIONS: Statistically based inferences were successfully drawn
      from PDF transforms of PXRD patterns obtained from composite systems. The
      principles applied herein may be universally adapted to many different systems
      and provide a fundamentally sound basis for drawing structural conclusions from
      PDF studies.

PMID- 20811929
TI  - Systems genetics, bioinformatics and eQTL mapping.
AB  - Jansen and Nap (Trends Genet 17(7):388-391, 2001) and Jansen (Nat Rev Genet 4:145
      151, 2003) first proposed the concept of genetical genomics, or genome-wide
      genetic analysis of gene expression data, which is also called transcriptome
      mapping. In this approach, microarrays are used for measuring gene expression
      levels across genetic mapping populations. These gene expression patterns have
      been used for genome-wide association analysis, an analysis referred to as
      expression QTL (eQTL) mapping. Recent progress in genomics and experimental
      biology has brought exponential growth of the biological information available
      for computational analysis in public genomics databases. Bioinformatics is
      essential to genome-wide analysis of gene expression data and used as an
      effective tool for eQTL mapping. The use of Plabsoft database, EcoTILLING, GNARE
      and FastMap allowed for dramatic reduction of time in genome analysis. Some web
      based tools (e.g., Lirnet, eQTL Viewer) provide efficient and intuitive ways for
      biologists to explore transcriptional regulation patterns, and to generate
      hypotheses on the genetic basis of transcriptional regulations. Expression
      quantitative trait loci (eQTL) mapping concerns finding genomic variation to
      elucidate variation of expression traits. This problem poses significant
      challenges due to high dimensionality of both the gene expression and the genomic
      marker data. The core challenges in understanding and explaining eQTL
      associations are the fine mapping and the lack of mechanistic explanation. But
      with the development of genetical genomics and computer technology, many new
      approaches for eQTL mapping will emerge. The statistical methods used for the
      analysis of expression QTL will become mature in the future.

PMID- 20811931
TI  - Real-time UV imaging of nicotine release from transdermal patch.
AB  - PURPOSE: This study was conducted to characterize UV imaging as a platform for
      performing in vitro release studies using Nicorette(r) nicotine patches as a
      model drug delivery system. METHODS: The rate of nicotine release from 2 mm
      diameter patch samples (Nicorette(r)) into 0.067 M phosphate buffer, pH 7.40, was
      studied by UV imaging (Actipix SDI300 dissolution imaging system) at 254 nm. The
      release rates were compared to those obtained using the paddle-over-disk method.
      RESULTS: Calibration curves were successfully established which allowed
      temporally and spatially resolved quantification of nicotine. Release profiles
      obtained from UV imaging were in qualitative agreement with results from the
      paddle-over-disk release method. CONCLUSION: Visualization as well as
      quantification of nicotine concentration gradients was achieved by UV imaging in
      real time. UV imaging has the potential to become an important technology
      platform for conducting in vitro drug release studies.

PMID- 20811932
TI  - Quantitative aspects of intracellularly-targeted drug delivery.

PMID- 20811933
TI  - Influence of dosing schedule on organ exposure to cyclosporin in pediatric
      hematopoietic stem cell transplantation: analysis with a PBPK model.
AB  - PURPOSE: Cyclosporin is administered by intermittent infusions (II) or continuous
      infusions (CI) to prevent acute graft-versus-host disease (aGVHD). Because
      cyclosporin disposition is nonlinear, organ exposure may be higher after II than
      after CI, but saturation of receptors must be accounted for. The aim of the study
      was to compare both types of administration using a mechanistic model. METHODS: A
      physiologically based pharmacokinetic model was developed to estimate cyclosporin
      exposure and receptor occupancies (RO) in aGVHD target organs and kidneys and to
      compare these estimations in pediatric patients that received cyclosporin either
      by II or CI. The relevant biological parameters were based on a clinical study in
      2 groups of pediatric patients that received cyclosporin either by II (n = 31) or
      CI (n = 30). RESULTS: Simulations showed that the exposure to cyclosporin in the
      interstitial fluid of aGVHD target organs was greater at day 1 after II than
      after CI. In kidneys, the opposite order was observed. AUC(RO) in all organs was
      greater after CI than after II. The therapeutic index (the ratio of AUC(RO) in
      blood to AUC(RO) in kidneys) was greater with CI than with II. CONCLUSIONS: CI
      may be slightly more favorable than II for aGVHD prevention.

PMID- 20811934
TI  - Application of plant viruses as nano drug delivery systems.
AB  - Nano-sized drug delivery systems based on virus-derived platforms have promising
      delivery and targeting efficiencies. To date, much of our understanding of these
      systems is obtained from studies of animal viruses. Application of plant viruses
      for drug delivery is in the nascent stage, but it is becoming apparent that plant
      viral particles can be engineered to possess novel properties to meet the unique
      requirements of targeted drug delivery. Chemical functionalization of a plant
      viral particle surface can impart stealth properties to prolong in vivo
      circulation half-life and/or targeting capability to direct drug delivery to
      diseased tissues. The amino acid sequence of the viral coat protein can be
      genetically manipulated to yield protein cages of specific chemistry and
      morphology, while the conformation of the protein cage can be directed, via the
      external environment, to disassemble, then reassemble in vitro to exchange native
      viral genomic material with exogenous cargo. The purpose of this commentary is to
      evaluate current literature to assess the potential of nano-scale plant-virus
      based drug delivery systems for the targeted delivery of chemotherapeutic agents.

PMID- 20811935
TI  - Crystallization of trehalose in frozen solutions and its phase behavior during
      drying.
AB  - PURPOSE: (i) To study the crystallization of trehalose in frozen solutions and
      (ii) to understand the phase transitions during the entire freeze-drying cycle.
      METHOD: Aqueous trehalose solution was cooled to -40 degrees C in a custom
      designed sample holder. The frozen solution was warmed to -18 degrees C and
      annealed, and then dried in the sample chamber of the diffractometer. XRD
      patterns were continuously collected during cooling, annealing and drying.
      RESULTS: After cooling, hexagonal ice was the only crystalline phase observed.
      However, upon annealing, crystallization of trehalose dihydrate was evident.
      Seeding the frozen solution accelerated the solute crystallization. Thus, phase
      separation of the lyoprotectant was observed in frozen solutions. During drying,
      dehydration of trehalose dihydrate yielded a substantially amorphous anhydrous
      trehalose. CONCLUSIONS: Crystallization of trehalose, as trehalose dihydrate, was
      observed in frozen solutions. The dehydration of the crystalline trehalose
      dihydrate to substantially amorphous anhydrate occurred during drying. Therefore,
      analyzing the final lyophile will not reveal crystallization of the lyoprotectant
      during freeze-drying. The lyoprotectant crystallization can only become evident
      by continuous monitoring of the system during the entire freeze-drying cycle. In
      light of the phase separation of trehalose in frozen solutions, its ability to
      serve as a lyoprotectant warrants further investigation.

PMID- 20811936
TI  - 'Real relationships': sociable interaction, material culture and imprisonment in
      a secure psychiatric unit.
AB  - Research into the character of social relationships in psychiatric inpatient
      facilities has focused on face-to-face interaction between individuals and within
      groups in the communal areas of wards. Using theories developed in material
      culture and media studies, this article argues that patients' relationships to
      goods, namely, photographs, cards and gifts from family or friends, televisions
      and radios, are important mediators and constituents of sociability. In an
      ethnographic study of a medium-secure psychiatric unit, I show how these goods
      are put to use in private space in ways that reflect and mitigate the constraints
      of incarceration and stigmatization. The data were derived from 3 months of
      participant observation on a male and a female ward at a unit in the south of
      England, including a series of anthropological interviews with 19 patients. This
      article highlights two important findings. First, potentially isolating
      activities are perceived by patients as sociable, in that watching television and
      looking at photographs in their room helps to counter feelings of loneliness and
      isolation. Second, potentially sociable activities, exchanging goods or watching
      the communal television, are often practiced in such a way as to maintain
      distance between patients in acknowledgment of the constrained and volatile
      nature of these relationships. This suggests that patients aspire to retain a
      sense of the artificiality of their situation, preferring to confine their notion
      of 'real' relationships to those that exist outside the institution.

PMID- 20811937
TI  - Cloning of complementary and genomic DNAs encoding echotoxins, proteinaceous
      toxins from the salivary gland of marine gastropod Monoplex echo.
AB  - Echotoxins are hemolytic and lethal proteinaceous toxins of about 25 kDa that are
      contained in the salivary gland of marine gastropod Monoplex echo. In this study,
      complementary DNAs (cDNAs) encoding four echotoxins (2, A, B1 and B2) were
      isolated from the cDNA library constructed from the M. echo salivary gland and
      completely sequenced. Although the amino acid sequence identity between the four
      echotoxins and actinoporins (20 kDa hemolysins from sea anemones) was very low
      (12-16%), some amino acid residues important for the biological activity of
      actinoporins were well conserved in the echotoxins. In the case of echotoxin 2,
      the genomic DNA corresponding to the coding region was amplified. Sequencing data
      revealed that the echotoxin 2 gene is devoid of introns within the coding region
      as reported for the actinoporin genes. These results suggest that echotoxins have
      evolved from actinoporins or both toxins have evolved from the same ancestor.

PMID- 20811939
TI  - Beyond sugar daddies: intergenerational sex and AIDS in urban Zimbabwe.
AB  - In a survey of 1,313 men reporting on 2,465 partnerships recruited at beer halls
      in Harare, Zimbabwe, 2.5% met a definition of "sugar daddy": men with a non
      marital partner at least 10 years younger and under 20 years old, and exchanged
      cash or goods for sex. Men engaging in intergenerational sex with a teenage woman
      had similar HIV prevalence, incomes, and condom use as men in other partnerships.
      Most men (62.3%) had partners 5 or more years younger, with wider age gaps in
      longer-term relationships. Condom use was less common within married and steady
      partnerships compared to casual and more common with younger women. The most
      common form of intergenerational sex, with the widest age gap and lowest condom
      use, occurs within marriages and steady partnerships. Such "conventional"
      intergenerational sex may play the pivotal role in sustaining a generalized
      epidemic across generations and present the most difficult challenge to
      prevention.

PMID- 20811938
TI  - Cathelicidin peptide LL-37 modulates TREM-1 expression and inflammatory responses
      to microbial compounds.
AB  - Inflammatory diseases remain an important cause of morbidity and mortality.
      Cathelicidins are immunomodulatory and antimicrobial peptides with potent anti
      endotoxic properties. Although the effects of the human cathelicidin LL-37 on
      cellular responses to Toll-like receptor (TLR) ligands have been investigated,
      its effects on responses to other pro-inflammatory stimuli have not been well
      studied. Triggering receptor expressed on myeloid cells (TREM-1) acts to amplify
      inflammatory responses and plays important roles in the pathogenesis of
      endotoxemia. In this work, the effects of LL-37 on responses to TREM-1
      stimulation, alone and in the presence of a range of microbial compounds, were
      analyzed. It was shown that in peripheral blood mononuclear cells LL-37 strongly
      suppressed synergistic responses to TREM-1 and TLR4 stimulation, partly through
      the inhibition of TREM-1 expression on monocytes; similar effects were observed
      using the TLR2 ligand lipoteichoic acid. In contrast, LL-37 stimulated TREM-1
      upregulation by peptidoglycan (PGN, TLR2 ligand that is also recognized via
      nucleotide-binding oligomerization domain containing 2 after fragmentation and
      intracellular uptake), as well as the responses to combined TREM-1 and PGN
      stimulation, possibly via the p38 mitogen-activated protein kinase pathway. LL-37
      did not affect TREM-1-induced neutrophil degranulation or the production of
      reactive oxygen species and interleukin-8 by neutrophils. These findings provide
      further insight into the roles of LL-37 during inflammation and may have
      implications for its in vivo immunomodulatory properties and for the design of
      synthetic cathelicidin derivatives as anti-inflammatory and anti-endotoxic
      molecules.

PMID- 20811940
TI  - Differentiation of sex chromosomes and karyotypic evolution in the eye-lid geckos
      (Squamata: Gekkota: Eublepharidae), a group with different modes of sex
      determination.
AB  - The eyelid geckos (family Eublepharidae) include both species with temperature
      dependent sex determination and species where genotypic sex determination (GSD)
      was suggested based on the observation of equal sex ratios at several incubation
      temperatures. In this study, we present data on karyotypes and chromosomal
      characteristics in 12 species (Aeluroscalabotes felinus, Coleonyx brevis,
      Coleonyx elegans, Coleonyx variegatus, Eublepharis angramainyu, Eublepharis
      macularius, Goniurosaurus araneus, Goniurosaurus lichtenfelderi, Goniurosaurus
      luii, Goniurosaurus splendens, Hemitheconyx caudicinctus, and Holodactylus
      africanus) covering all genera of the family, and search for the presence of
      heteromorphic sex chromosomes. Phylogenetic mapping of chromosomal changes showed
      a long evolutionary stasis of karyotypes with all acrocentric chromosomes
      followed by numerous chromosomal rearrangements in the ancestors of two lineages.
      We have found heteromorphic sex chromosomes in only one species, which suggests
      that sex chromosomes in most GSD species of the eyelid geckos are not
      morphologically differentiated. The sexual difference in karyotype was detected
      only in C. elegans which has a multiple sex chromosome system (X(1)X(2)Y). The
      metacentric Y chromosome evolved most likely via centric fusion of two
      acrocentric chromosomes involving loss of interstitial telomeric sequences. We
      conclude that the eyelid geckos exhibit diversity in sex determination ranging
      from the absence of any sexual differences to heteromorphic sex chromosomes,
      which makes them an interesting system for exploring the evolutionary origin of
      sexually dimorphic genomes.

PMID- 20811941
TI  - Selection against Robertsonian fusions involving housekeeping genes in the house
      mouse: integrating data from gene expression arrays and chromosome evolution.
AB  - Monobrachial homology resulting from Robertsonian (Rb) fusions is thought to
      contribute to chromosomal speciation through underdominance. Given the karyotypic
      diversity characterizing wild house mouse populations [Mus musculus domesticus,
      (MMU)], variation that results almost exclusively from Rb fusions (diploid
      numbers range from 22 to 40) and possibly whole arm reciprocal translocations
      (WARTs), this organism represents an excellent model for testing hypotheses of
      chromosomal evolution. Previous studies of chromosome size and recombination
      rates have failed to explain the bias for certain chromosomes to be involved more
      frequently than others in these rearrangements. Here, we show that the
      pericentromeric region of one such chromosome, MMU19, which is infrequently
      encountered as a fusion partner in wild populations, is significantly enriched
      for housekeeping genes when compared to other chromosomes in the genome. These
      data suggest that there is selection against breakpoints in the pericentromeric
      region and provide new insights into factors that constrain chromosomal
      reorganizations in house mice. Given the anticipated increase in vertebrate whole
      genome sequences, the examination of gene content and expression profiles of the
      pericentromeric regions of other mammalian lineages characterized by Rb fusions
      (i.e., other rodents, bats, and bovids, among others) is both achievable and
      crucial to developing broadly applicable models of chromosome evolution.

PMID- 20811943
TI  - Biomonitoring approach with mussel Mytilus galloprovincialis (Lmk) and clam
      Ruditapes philippinarum (Adams and Reeve, 1850) in the Lagoon of Venice.
AB  - Transplanted Mytilus galloprovincialis and native Ruditapes philippinarum were
      deployed in 10 sampling stations with different pollution impact within the
      Lagoon of Venice to evaluate the temporal variations and the suitability of the
      following cytochemical and histochemical biomarkers just as indicators of
      environmental stress: lysosomal membrane stability, lipofuscins, neutral lipids
      and lysosome to cytoplasm volume ratio. The physiological status of the organisms
      was also investigated by determining the survival in air capability and the
      reburrowing rate (clams). The biological parameters were assessed in June and
      October. Furthermore, for a better definition of the environmental aspects of the
      study sites, heavy metal, PAH and PCB concentrations were also evaluated in the
      sediments. As a whole, the biological responses examined in both species from all
      the sampling sites showed significant differences between the two seasonal
      campaigns, only lysosomal membrane stability exhibited less variability.
      Pollutants in sediments generally showed low-intermediate contamination levels,
      few hotspots persisting mostly in the inner areas of the lagoon, the most
      influenced by the industrial zone. Transplanted mussels were more responsive than
      native clams and the biological responses of both species varied temporally. The
      range of the spatial variability was always narrow and reflected only partially
      the broader variability shown by the chemical content in the sediments. In this
      sense, biological responses seemed to be particularly influenced by the high
      temporal and spatial heterogeneity that characterise the Lagoon of Venice, as
      well as most of the transitional environments.

PMID- 20811945
TI  - The 4th Japan and US Collaboration Conference in Gastroenterology.

PMID- 20811944
TI  - Is there room for 'development' in developmental models of information processing
      biases to threat in children and adolescents?
AB  - Clinical and experimental theories assume that processing biases in attention and
      interpretation are a causal mechanism through which anxiety develops. Despite
      growing evidence that these processing biases are present in children and,
      therefore, develop long before adulthood, these theories ignore the potential
      role of child development. This review attempts to place information processing
      biases within a theoretical developmental framework. We consider whether child
      development has no impact on information processing biases to threat (integral
      bias model), or whether child development influences information processing
      biases and if so whether it does so by moderating the expression of an existing
      bias (moderation model) or by affecting the acquisition of a bias (acquisition
      model). We examine the extent to which these models fit with existing theory and
      research evidence and outline some methodological issues that need to be
      considered when drawing conclusions about the potential role of child development
      in the information processing of threat stimuli. Finally, we speculate about the
      developmental processes that might be important to consider in future research.

PMID- 20811946
TI  - Cognitive functions of the cerebellum.

PMID- 20811947
TI  - The cerebellum and basal ganglia are interconnected.
AB  - The cerebellum and the basal ganglia are major subcortical nuclei that control
      multiple aspects of behavior largely through their interactions with the cerebral
      cortex. Discrete multisynaptic loops connect both the cerebellum and the basal
      ganglia with multiple areas of the cerebral cortex. Interactions between these
      loops have traditionally been thought to occur mainly at the level of the
      cerebral cortex. Here, we review a series of recent anatomical studies in
      nonhuman primates that challenge this perspective. We show that the anatomical
      substrate exists for substantial interactions between the cerebellum and the
      basal ganglia. Furthermore, we discuss how these pathways may provide a useful
      framework for understanding cerebellar contributions to the manifestation of two
      prototypical basal ganglia disorders, Parkinson's disease and dystonia.

PMID- 20811948
TI  - Tyrosine kinase inhibitor PTK/ZK enhances the antitumor effects of interferon
      alpha/5-fluorouracil therapy for hepatocellular carcinoma cells.
AB  - PURPOSE: There is no standardized treatment for hepatocellular carcinoma (HCC)
      with portal vein tumor thrombus. We previously reported the efficacy of
      interferon-alpha and 5-fluorouracil combination (IFN/5-FU) therapy for these
      patients and the potential mechanism via the regulation of vascular endothelial
      growth factor (VEGF). In this study, we showed the VEGF-related effects of IFN/5
      FU therapy using VEGF-receptor (VEGFR) selective inhibitor, PTK787/ZK222584
      (PTK/ZK), in HCC cells. METHODS: Using two VEGF secreting and VEGFR expressing
      human HCC cell lines, PLC/PRF/5 and HuH7, we performed growth inhibitory assays
      in vitro and in vivo, apoptosis assay, cell cycle analysis, and Western blot
      analysis for the mechanism, with or without PTK/ZK in IFN/5-FU therapy. RESULTS:
      The combination of PTK/ZK and IFN/5-FU significantly inhibited cell growth in
      vitro and tended to reduce tumor growth in vivo in a HuH7 xenograft model in nude
      mice-in both cases without affecting VEGF secretion. PTK/ZK enhanced the IFN/5-FU
      induced apoptosis, based on increased proteins levels of Bax and reduced Bcl-xL
      and Bcl-2. Cell cycle analysis showed different results between the HCC cell
      lines following the combination therapy, possibly due to differences in p21
      protein. CONCLUSIONS: VEGF signaling inhibition would support an antitumor effect
      of IFN/5-FU therapy against HCC cell lines via induction of apoptosis and cell
      cycle delay.

PMID- 20811949
TI  - Comparison of p53 and epidermal growth factor receptor gene status between
      primary tumors and lymph node metastases in non-small cell lung cancers.
AB  - BACKGROUND: To obtain insight into the cancer progression and metastatic process,
      we evaluate p53/epidermal growth factor receptor (EGFR) somatic aberrations in
      non-small-cell lung cancers to compare accumulated genetic alterations between
      primary tumors and lymph node metastases. MATERIALS AND METHODS: A total of 56
      primary lung cancers with corresponding lymph node metastases were identified to
      investigate somatic mutations and altered expressions of p53 and EGFR for
      clonality assessment. Genomic DNA was extracted from macrodissected cells of
      paraffin-embedded primary tumor and metastatic lymph node tissues. Overexpression
      and somatic mutations in exons of p53 (exons 5-8) and tyrosine kinase domain of
      EGFR (exons 18-21) were examined by immunohistochemical staining and DNA
      sequencing, respectively. RESULTS: p53 and EGFR mutation/overexpression status
      were different between primary tumors and lymph node metastases in 5.4/7.2% and
      28.6/33.9%, respectively. In most cases, the p53 and EGFR mutations usually
      preceded lymph node metastasis, and these gene statuses in the primary cancer and
      their lymph node metastasis were concordant (92.9 and 69.6%, respectively), which
      further supported the hypothesis that when these p53 mutations occur before the
      establishment of lymph node metastasis, they subsequently persist in the
      metastatic nodes. The expressions of p53 and EGFR showed 7.1 and 33.9%
      discordance in that order. CONCLUSIONS: Our results reveal that p53 and EGFR
      mutations usually precede lymph node metastasis. The higher prevalence of EGFR
      heterogeneity existing in the primary tumor is not reflected in all lymph node
      metastasis and thus might have therapeutic implications when adjuvant therapy is
      considered.

PMID- 20811950
TI  - Lipid metabolism in long-lived families: the Leiden Longevity Study.
AB  - Mechanisms underlying the variation in human life expectancy are largely unknown,
      but lipid metabolism and especially lipoprotein size was suggested to play an
      important role in longevity. We have performed comprehensive lipid phenotyping in
      the Leiden Longevity Study (LLS). By applying multiple logistic regression
      analysis we tested for the first time the effects of parameters in lipid
      metabolism (i.e., classical serum lipids, lipoprotein particle sizes, and
      apolipoprotein E levels) on longevity independent of each other. Parameters in
      lipid metabolism were measured in offspring of nonagenarian siblings from 421
      families of the LLS (n = 1,664; mean age, 59 years) and in the partners of the
      offspring as population controls (n = 711; mean age, 60 years). In the initial
      model, where lipoprotein particles sizes, classical serum lipids and
      apolipoprotein E were included, offspring had larger low-density lipoprotein
      (LDL) particle sizes (p = 0.017), and lower triglyceride levels (p = 0.026),
      indicating that they displayed a more beneficial lipid profile. After backwards
      regression only LDL size (p = 0.014) and triglyceride levels (p = 0.05) were
      associated with offspring from long-lived families. Sex-specific backwards
      regression analysis revealed that LDL particle sizes were associated with male
      longevity (increase in log odds ratio (OR) per unit = 0.21; p = 0.023).
      Triglyceride levels (decrease OR per unit = 0.22; p = 0.01), but not LDL particle
      size, were associated with female longevity. Due to the analysis of a
      comprehensive lipid profile, we confirmed an important role of lipid metabolism
      in human longevity, with LDL size and triglyceride levels as major predicting
      factors.

PMID- 20811951
TI  - A tale of two obesCities: the role of municipal governance in reducing childhood
      obesity in New York City and London.
AB  - As rates of childhood obesity and overweight rise around the world, researchers
      and policy makers seek new ways to reverse these trends. Given the concentration
      of the world's population, income inequalities, unhealthy diets, and patterns of
      physical activity in cities, urban areas bear a disproportionate burden of
      obesity. To address these issues, in 2008, researchers from the City University
      of New York and London Metropolitan University created the Municipal Responses to
      Childhood Obesity Collaborative. The Collaborative examined three questions: What
      role has city government played in responding to childhood obesity in each
      jurisdiction? How have municipal governance structures in each city influenced
      its capacity to respond effectively? How can policy and programmatic
      interventions to reduce childhood obesity also reduce the growing socioeconomic
      and racial/ethnic inequities in its prevalence? Based on a review of existing
      initiatives in London and New York City, the Collaborative recommended 11 broad
      strategies by which each city could reduce childhood obesity. These
      recommendations were selected because they can be enacted at the municipal level;
      will reduce socioeconomic and racial/ethnic inequalities in obesity; are either
      well supported by research or are already being implemented in one city,
      demonstrating their feasibility; build on existing city assets; and are both
      green and healthy.

PMID- 20811952
TI  - A pilot binational study of health behaviors and immigration.
AB  - In the US, Mexican immigrant women often have better health outcomes than non
      Hispanic white women despite a greater health risk profile. This cross-sectional
      pilot study compared women living in Chavinda, Michoacan (n = 102) to women who
      had migrated from Mexico to Madera, California (n = 93). The interview gathered
      information on acculturation and risk behaviors including smoking, alcohol use
      and number of sexual partners. The results suggest that more acculturated women
      living in the US are more likely to consume alcohol. US residence and higher
      acculturation level was marginally associated with having more than one sexual
      partner. There were no differences between odds of smoking among Chavinda and
      Madera women. While results with acculturation are not consistently significant
      due to small sample sizes, the results are suggestive that acculturation among
      immigrant Hispanic women in the US may be associated with adverse health
      behaviors, and selective migration seems less likely to account for these
      differences.

PMID- 20811953
TI  - Self-reported urge urinary incontinence (UUI) among older Mexican-American men:
      risk factors and psycho-social consequences.
AB  - Extant literature on Urge Urinary Incontinence (UUI) focuses on women and non
      Hispanic Whites and little is known about ethnic minority men. We analyzed 700
      Mexican-American men aged 75 and older from the fifth Wave (2004/5) of the
      Hispanic Established Population for the Epidemiologic Study of the Elderly.
      Logistic regression analyses examined risk factors for self-reported UUI and the
      impact of UUI on mental health and social support. Twenty-nine percent reported
      having difficulty holding their urine until they could get to a toilet. Men with
      more co-morbid conditions and men with prostate problems were more likely to
      report UUI symptoms. Men with UUI were less likely to report having a confidant
      and had a higher risk of high depressive symptoms. This study is the first to
      examine risk factors for and consequences of self-reported UUI among older
      Mexican-American men using a large community-based survey.

PMID- 20811954
TI  - Modeling of hemodialysis operation.
AB  - In this study, a theoretical model was developed to predict the solute
      concentrations in patients' blood and optimize the efficiency of the hemodialysis
      operation. The model takes into account simultaneous mass and momentum transfer
      on the blood side both in radial and axial directions. A key component of the
      model is the incorporation of the protein adsorption on the inner surface of the
      membrane. The validity of the model was confirmed with the experimental data
      available in the literature for two different types of hemodiafilter. To
      illustrate the importance of including the radial concentration gradients and
      protein adsorption kinetics in the model, the experimental data were predicted
      with and without consideration of these effects. The results have shown that
      assuming uniform concentration in the radial direction or neglecting protein
      adsorption on the inner surface of the membrane leads to higher error in
      predicting the experimental data. In addition, significant error can be
      introduced in the calculation of the dialysis time if protein adsorption is not
      considered.

PMID- 20811955
TI  - Monte Carlo investigation of diffusion of receptors and ligands that bind across
      opposing surfaces.
AB  - Studies of receptor diffusion on a cell surface show a variety of behaviors, such
      as diffusive, sub-diffusive, or super-diffusive motion. However, most studies to
      date focus on receptor molecules diffusing on a single cell surface. We have
      previously studied receptor diffusion to probe the molecular mechanism of
      receptor clustering at the cell-cell junction between two opposing cell surfaces.
      Here, we characterize the diffusion of receptors and ligands that bind to each
      other across two opposing cell surfaces, as in cell-cell and cell-bilayer
      interactions. We use a Monte Carlo method, where receptors and ligands are
      simulated as independent agents that bind and diffuse probabilistically. We vary
      receptor-ligand binding affinity and plot the molecule-averaged mean square
      displacement (MSD) of ligand molecules as a function of time. Our results show
      that MSD plots are qualitatively different for flat and curved interfaces, as
      well as between the cases of presence and absence of directed transport of
      receptor-ligand complexes toward a specific location on the interface. Receptor
      ligand binding across two opposing surfaces leads to transient sub-diffusive
      motion at early times provided the interface is flat. This effect is entirely
      absent if the interface is curved, however, in this instance we observe sub
      diffusive motion. In addition, a decrease in the equilibrium value of the MSD
      occurs as affinity increases, something which is absent for a flat interface. In
      the presence of directed transport of receptor-ligand complexes, we observe super
      diffusive motion at early times for a flat interface. Super-diffusive motion is
      absent for a curved interface, however, in this case we observe a transient
      decrease in MSD with time prior to equilibration for high-affinity values.

PMID- 20811956
TI  - Patient care outside of office visits: a primary care physician time study.
AB  - BACKGROUND: Patient care provided by primary care physicians outside of office
      visits is important for care coordination and may serve as a substitute for
      office visits. OBJECTIVES: To describe primary care physicians' ambulatory
      patient care activities outside of office visits ("AOVs") and their perceptions
      of the extent to which AOVs substitute for visits and may be performed by support
      staff. DESIGN: Cross-sectional direct observational study. PARTICIPANTS: Thirty
      three general internists in 20 practices in two health care systems (one public,
      one private) in the New York metropolitan area. MAIN MEASURES: Duration of AOVs
      by type of activity and whether they pertain to a patient visit on the study day
      (visit specific) or not (non-visit specific). Physician perceptions of the: (1)
      extent that non-visit-specific AOVs substitute for visits that would have
      otherwise occurred, (2) extent that visits that occurred could have been
      substituted for by AOVs, and (3) potential role of support staff in AOVs. KEY
      RESULTS: Physicians spent 20% of their workday performing AOVs, 62% of which was
      for non-visit specific AOVs. They perceived that a median of 37% of non-visit
      specific AOV time substituted for visits, representing a potential five visits
      saved per day. They also perceived that 15% of total AOV time (excluding
      charting) could be performed by support staff. Forty-two percent of physicians
      indicated that one or more visits during the study day could be substituted for
      by AOVs. CONCLUSIONS: Though time spent on AOVs is generally not reimbursed,
      primary care general internists spent significant time performing AOVs, much of
      which they perceived to substitute for visits that would otherwise have occurred.
      Policies supporting physician and staff time spent on AOVs may reduce health care
      costs, save time for patients and physicians, and improve care coordination.

PMID- 20811957
TI  - High-risk pools for the sick and uninsured under health reform: too little and
      thus too late.
AB  - Democrats and Republicans have turned to the concept of "high-risk pools" to
      provide health care for those Americans who face the dual challenge of
      uninsurance and serious health difficulties. Under the Patient Protection and
      Affordable Care Act (PPACA), these "high-risk" individuals will receive extensive
      help and regulatory protections, in concert with a new system of health insurance
      exchanges. However, these federal provisions do not become operational until
      2014. As an interim measure, PPACA provides $5 billion for temporary, federally
      funded high-risk pools, now known as the Pre-Existing Condition Insurance Plan
      (PCIP). This analysis explores the adequacy of such funding. Using 2005/06 data
      from the National Health and Nutrition Examination Survey (NHANES), we find that
      approximately 4 million uninsured Americans have been diagnosed with emphysema,
      diabetes, stroke, cancer, congestive heart failure, angina, or a heart attack. To
      provide adequate health care for uninsured individuals with chronic diseases, the
      federal PCIP appropriations would need to be many times higher than either
      Democrats or Republicans have proposed.

PMID- 20811958
TI  - Weight loss outcome after silastic ring Roux-en-Y gastric bypass: 8 years of
      follow-up.
AB  - BACKGROUND: An underlying major aim of bariatric surgery is weight loss and its
      long-term maintenance. In spite of this, most studies regarding weight loss after
      surgical treatment of morbid obesity show 3-year follow-up results. We evaluated
      the effectiveness of silastic ring Roux-en-Y gastric bypass (SR-RYGBP) in
      promoting significant weight loss after an 8-year follow-up at the Londrina State
      University Hospital. METHODS: From May 1999 to December 2000, 211 morbidly obese
      patients were submitted to SR-RYGBP by the same surgical team. The study's design
      was longitudinal, prospective, and descriptive. The analysis of postoperative
      weight decrease was based on excess weight loss in percentage (%EWL) and the
      calculation of body mass index. Therapeutic failure was considered when patients
      lost <50% of excess weight. RESULTS: Patients lost to follow-up were 36.5%;
      therefore, 134 patients were included in this study. The average global EWL was
      67.6 +/- 14.9% on the first postoperative year, 72.6 +/- 14.9% on the second
      year, 69.7 +/- 15.1% on the fifth postoperative year, and 66.8 +/- 7.6% on the
      eight postoperative year. Surgical treatment failure occurred in 15 patients
      (7.1%) over 8 years. CONCLUSIONS: SR-RYGBP was effective in promoting and
      maintaining weight loss in the long term with a low failure rate.

PMID- 20811959
TI  - An exopolysaccharide from cultivated Cordyceps sinensis and its effects on
      cytokine expressions of immunocytes.
AB  - The exopolysaccharide (EPS) is a polysaccharide from cultivated Cordyceps
      sinensis, which possesses immunomodulatory and antitumor effects, was purified by
      DEAE-32 cellulose and Sephadex G-200 gel. The preliminary characters of EPS were
      analyzed by IR and GC, and the molecular weight was estimated by gel filtration.
      The effect of EPS on proliferation ability of lymphocytes from ICR mice was
      assayed by MTT method. The mRNA and protein expression levels of several
      cytokines in spleen and thymus cells were detected by RT-PCR and ELISA. The
      results showed that EPS consists of mannose, glucose, and galactose in a ratio of
      23:1:2.6. Its molecular weight is about 1.04 * 10(5). EPS elevated proliferation
      ability of spleen lymphocytes only at 100 MUg/ml after 48 h treatment. Tumor
      necrosis factor alpha (TNF-alpha), interferon-alpha (IFN-gamma), and interleukin
      2 (IL-2) mRNA levels in splenocytes and thymocytes were increased after EPS
      treatment for 2, 4, 8, or 20 h. EPS also significantly elevated splenic TNF-alpha
      and IFN-gamma protein expressions at 100 MUg/ml and increased thymic TNF-alpha
      and IFN-gamma protein levels at 50 and 100 MUg/ml. These data indicated that EPS
      may stimulate cytokine expressions of immunocytes.

PMID- 20811960
TI  - Monitoring of circadian rhythms of heart rate, locomotor activity, and
      temperature for diagnosis and evaluation of response to treatment in an animal
      model of depression.
AB  - Depressive disorders affect approximately 5% of the population in developed
      countries each year. Current antidepressant treatment usually requires several
      weeks to obtain response or remission and is only effective in about half of
      depressed patients. Objective diagnostic tools and detection of symptom relief by
      physiological biomarkers may assist in the clinical decision-making process
      regarding the selection, replacing, and augmenting of antidepressants.
      Furthermore, such biomarkers may enable early prediction of the appropriateness
      of a specific antidepressant for a particular patient. Here, we examined a new
      non-invasive method for objective diagnosis of depressive-like behavior and for
      the purpose of predicting antidepressant (paroxetine and desipramine) treatment
      effectiveness. This method employed a genetic rat model of depression and
      mathematical analysis of physiological parameters, of circadian rhythms of heart
      rate, locomotor activity, and temperature for diagnosis and evaluation of
      response to treatment in an animal model of depression. By utilizing this method,
      we were able to discern, in a rat model, between depressive and non-depressive
      individuals and to predict beneficial response to the antidepressants.
      Mathematical analysis of physiological parameters such as heart rate, locomotor
      activity, and temperature circadian rhythms can be used for objective diagnosis
      of depressive-like behavior and for early prediction of response to
      antidepressant treatment.

PMID- 20811961
TI  - Response to the Letter to the Editor from Gustavo Cartaxo Patriota, M.D., M.Sc.,
      on "Clinical Grading Scales in Intracerebral Hemorrhage"

PMID- 20811962
TI  - H1N1 encephalitis with malignant edema and review of neurologic complications
      from influenza.
AB  - BACKGROUND: Influenza virus infection of the respiratory tract is associated with
      a range of neurologic complications. The emergence of 2009 pandemic influenza A
      (H1N1) virus has been linked to neurological complications, including
      encephalopathy and encephalitis. METHODS: Case report and literature review.
      RESULTS: We reviewed case management of a 20-year old Hispanic male who developed
      febrile upper respiratory tract signs and symptoms followed by a confusional
      state. He had rapid neurologic decline and his clinical course was complicated by
      refractory seizures and malignant brain edema. He was managed with oseltamavir
      and peramavir, corticosteroids, intravenous gamma globulin treatment,
      anticonvulsants, intracranial pressure management with external ventricular drain
      placement, hyperosmolar therapy, sedation, and mechanical ventilation. Reverse
      transcriptase polymerase chain reaction analysis of nasal secretions confirmed
      2009 H1N1 virus infection; cerebrospinal fluid (CSF) was negative for 2009 H1N1
      viral RNA. Follow-up imaging demonstrated improvement in brain edema but
      restricted diffusion in the basal ganglia. We provide a review of the clinical
      spectrum of neurologic complications of seasonal influenza and 2009 H1N1, and
      current approaches towards managing these complications. CONCLUSIONS: 2009 H1N1
      associated acute encephalitis and encephalopathy appear to be variable in
      severity, including a subset of patients with a malignant clinical course
      complicated by high morbidity and mortality. Since the H1N1 influenza virus has
      not been detected in the CSF or brain tissue in patients with this diagnosis, the
      emerging view is that the host immune response plays a key role in pathogenesis.

PMID- 20811963
TI  - The utility and limitations of FRAX: A US perspective.
AB  - The FRAX calculator is a major achievement in terms of our understanding of
      measuring fracture risk. Along with being an easily accessible web-based tool, it
      is the only model based on extensive data on multiple cohorts. FRAX will help
      clinicians identify individuals who need osteoporosis treatments, while also
      screening out those who do not require osteoporosis treatments. However, FRAX is
      limited by a number of factors. Although it is web based, few physicians have the
      means to access it. It also assumes that body mass index and mortality are
      constant across different racial and ethnic groups. FRAX is further limited by
      the exclusion of variables known to be associated with fracture risk, lack of
      dose-response relationships for variables, increased subsequent fracture risk
      after initial fracture, restriction to only one bone mineral density site, racial
      and ethnic differences that may influence fracture risk, and availability of
      racial and ethnic fracture risk data to be used in the FRAX calculator. Finally,
      the values obtained from FRAX should not take the place of good clinical
      judgment.

PMID- 20811965
TI  - Clinical trials report: pazopanib for advanced renal cell carcinoma: comments on
      the results from the phase 3 study.

PMID- 20811964
TI  - The definition and clinical significance of nonvertebral fractures.
AB  - Nonvertebral fractures form the bulk of osteoporotic fractures and yet, other
      than hip fractures, are often dismissed, particularly in the younger age groups.
      Thus, less than 30% of women with osteoporotic fractures and less than 10% of men
      worldwide are receiving appropriate treatment. This article discusses the
      incidence, cost, and consequences of nonvertebral fractures. Recent evidence
      suggests these fractures form the bulk of costs to the community and herald an
      increased risk of refracture and premature mortality that applies to all types of
      nonvertebral, and not just hip, fractures.

PMID- 20811966
TI  - Application of method suitability for drug permeability classification.
AB  - Experimental models of permeability in animals, excised tissues, cell monolayers,
      and artificial membranes are important during drug discovery and development as
      permeability is one of several factors affecting the intestinal absorption of
      oral drug products. The utility of these models is demonstrated by their ability
      to predict a drug's in vivo intestinal absorption. Within the various
      permeability models, there are differences in the performance of the assays,
      along with variability in animal species, tissue sources, and cell types,
      resulting in a variety of experimental permeability values for the same drug
      among laboratories. This has led to a need for assay standardization within
      laboratories to ensure applicability in the drug development process. Method
      suitability provides a generalized approach to standardize and validate a
      permeability model within a laboratory. First, assay methodology is optimized and
      validated for its various experimental parameters along with acceptance criteria
      for the assay. Second, the suitability of the model is demonstrated by a rank
      order relationship between experimental permeability values and human extent of
      absorption of known model compounds. Lastly, standard compounds are employed to
      classify a test drug's intestinal permeability and ensure assay reproducibility
      and quality. This review will provide examples of the different aspects method
      suitability for in situ (intestinal perfusions), ex vivo (everted intestinal
      sacs, diffusion chambers), and in vitro (cell monolayers, artificial membranes)
      experimental permeability models. Through assay standardization, reference
      standards, and acceptance criteria, method suitability assures the dependability
      of experimental data to predict a drug's intestinal permeability during
      discovery, development, and regulatory application.

PMID- 20811969
TI  - 2010 Guidelines and international standards to the practice of anesthesia.

PMID- 20811967
TI  - Hemoglobin-derived peptides as novel type of bioactive signaling molecules.
AB  - Most bioactive peptides are generated by proteolytic cleavage of large precursor
      proteins followed by storage in secretory vesicles from where they are released
      upon cell stimulation. Examples of such bioactive peptides include peptide
      neurotransmitters, classical neuropeptides, and peptide hormones. In the last
      decade, it has become apparent that the breakdown of cytosolic proteins can
      generate peptides that have biological activity. A case in point and the focus of
      this review are hemoglobin-derived peptides. In vertebrates, hemoglobin (Hb)
      consists of a tetramer of two alpha- and two beta-globin chains each containing a
      prosthetic heme group, and is primarily involved in oxygen delivery to tissues
      and in redox reactions (Schechter Blood 112:3927-3938, 2008). The presence of
      alpha- and/or beta-globin chain in tissues besides red blood cells including
      rodent and human brain and peripheral tissues (Liu et al. Proc Natl Acad Sci USA
      96:6643-6647, 1999; Newton et al. J Biol Chem 281:5668-5676, 2006; Wride et al.
      Mol Vis 9:360-396, 2003; Setton-Avruj Exp Neurol 203:568-578, 2007; Ohyagi et al.
      Brain Res 635:323-327, 1994; Schelshorn et al. J Cereb Blood Flow Metab 29:585
      595, 2009; Richter et al. J Comp Neurol 515:538-547, 2009) suggests that globins
      and/or derived peptidic fragments might play additional physiological functions
      in different tissues. In support of this hypothesis, a number of Hb-derived
      peptides have been identified and shown to have diverse functions (Ivanov et al.
      Biopoly 43:171-188, 1997; Karelin et al. Neurochem Res 24:1117-1124, 1999).
      Modern mass spectrometric analyses have helped in the identification of
      additional Hb peptides (Newton et al. J Biol Chem 281:5668-5676, 2006; Setton
      Avruj Exp Neurol 203:568-578, 2007; Gomes et al. FASEB J 23:3020-3029, 2009); the
      molecular targets for these are only recently beginning to be revealed. Here, we
      review the status of the Hb peptide field and highlight recent reports on the
      identification of a molecular target for a novel set of Hb peptides,
      hemopressins, and the implication of these peptides to normal cell function and
      disease. The potential therapeutic applications for these Hb-derived hemopressin
      peptides will also be discussed.

PMID- 20811968
TI  - Chronic kidney disease and risk for coronary events: value of myocardial
      perfusion imaging.

PMID- 20811970
TI  - Brief review: Airway rescue with insertion of laryngeal mask airway devices with
      patients in the prone position.
AB  - PURPOSE: Unintentional extubation of the trachea while the anesthetized patient
      is in the prone position is a potentially life-threatening situation that is
      usually managed by turning the patient supine for emergent re-intubation.
      However, this approach may delay definitive airway management and lead to
      irreversible complications. This review evaluates the efficacy of insertion of a
      laryngeal mask airway device (LMAD) with the patient in the prone position as a
      rescue method in airway management for unintentional tracheal extubation.
      PRINCIPAL FINDINGS: We searched MEDLINE and EMBASE databases in the English
      language for the period 1980 to October 2009 in order to identify observational
      studies and case reports describing insertion of the LMAD with the patient in the
      prone position. We found 12 such articles (n = 526 patients) consisting of four
      retrospective studies, one prospective cohort with a control group, one non
      controlled prospective study, and six case reports. On the first attempt, the
      LMAD was inserted successfully in 87.5-100% of the patients involved in the
      included reports. On the second attempt, the LMAD was inserted successfully in
      all patients, with or without laryngoscopy. Ventilation was maintained
      successfully in the lungs of 83.3-100% of the patients involved in the reported
      articles. Following insertion of the LMAD with patients in the prone position,
      the most common complications reported were sore throat, bleeding, bradycardia,
      and laryngospasm. CONCLUSIONS: Cumulative experience from published reports
      suggests the feasibility of placing the LMAD with the patient in the prone
      position in the elective setting; however, the evidence is lacking regarding the
      use of this method for emergency management of unintended tracheal extubation
      with the patient in the prone position.

PMID- 20811971
TI  - [Dear colleagues and lecture courses].

PMID- 20811972
TI  - [Dear members of the German Society for the Study of Pain].

PMID- 20811974
TI  - The MAP kinase signaling cascades: a system of hundreds of components regulates a
      diverse array of physiological functions.
AB  - Sequential activation of kinases within the mitogen-activated protein (MAP)
      kinase (MAPK) cascades is a common, and evolutionary-conserved mechanism of
      signal transduction. Four MAPK cascades have been identified in the last 20 years
      and those are usually named according to the MAPK components that are the central
      building blocks of each of the cascades. These are the extracellular signal
      regulated kinase 1/2 (ERK1/2), c-Jun N-Terminal kinase (JNK), p38, and ERK5
      cascades. Each of these cascades consists of a core module of three tiers of
      protein kinases termed MAPK, MAPKK, and MAP3K, and often two additional tiers,
      the upstream MAP4K and the downstream MAPKAPK, which can complete five tiers of
      each cascade in certain cell lines or stimulations. The transmission of the
      signal via each cascade is mediated by sequential phosphorylation and activation
      of the components in the sequential tiers. These cascades cooperate in
      transmitting various extracellular signals and thus control a large number of
      distinct and even opposing cellular processes such as proliferation,
      differentiation, survival, development, stress response, and apoptosis. One way
      by which the specificity of each cascade is regulated is through the existence of
      several distinct components in each tier of the different cascades. About 70
      genes, which are each translated to several alternatively spliced isoforms,
      encode the entire MAPK system, and allow the wide array of cascade's functions.
      These components, their regulation, as well as their involvement together with
      other mechanisms in the determination of signaling specificity by the MAPK
      cascade is described in this review. Mis-regulation of the MAPKs signals usually
      leads to diseases such as cancer and diabetes; therefore, studying the mechanisms
      of specificity-determination may lead to better understanding of these signaling
      related diseases.

PMID- 20811975
TI  - Determination of ERK activity: anti-phospho-ERK antibodies and in vitro
      phosphorylation.
AB  - The ERK signaling cascade is composed of several protein kinases that
      sequentially activate each other by phosphorylation. This pathway is a central
      component of a complex signaling network that regulates important cellular
      processes including proliferation, differentiation, and survival. In most of
      these cases, the ERK cascade is activated downstream of the small GTPase Ras
      that, upon activation, recruits and activates the first tier in the cascade,
      which contains the Raf kinases. Afterward the signal is further transmitted by
      MEKs, ERKs, and often RSKs in the MAPKK, MAPK, and MAPKAPKs tiers of the cascade,
      respectively. ERKs and RSKs can further disseminate the signal by phosphorylating
      and modulating the activity of a large number of regulatory proteins including
      transcription factors and chromatin modifying enzymes. Understanding the
      mechanisms of activation and the regulation of the various components of this
      cascade will enhance our insight into the regulation of the ERK-dependent
      cellular processes in normal cells or of their malfunctioning in various
      diseases, including cancer. In this chapter, we describe methods used to
      determine the activity of ERKs, which upon slight modifications can also be used
      for the study of other signaling kinases, either within the cascade or in other
      pathways. These methods have been successfully applied to study the ERK signaling
      cascades in a variety of tissue-cultured cell lines, homo-genized animal organs,
      and lower organisms. As such, the use of these methods should expand our
      knowledge on the regulation of many distinct systems and upon induction of
      various stimulations.

PMID- 20811976
TI  - Activation of SAPK/JNKs in vitro.
AB  - The stress-activated protein kinase/c-jun N-terminal kinases (SAPK/JNKs) are
      mitogen-activated protein kinases (MAPKs) that are activated by stressful and
      inflammatory stimuli and regulate cellular responses such as proliferation,
      differentiation, and apoptosis. The SAPK/JNKs are phosphorylated and activated by
      the MAP kinase kinases (MAP2Ks), SEK1/MKK4 and MKK7. These MAP2Ks are
      phosphorylated and activated by upstream stress-activated MAPK kinase kinases
      (MAP3Ks). Upon activation, SAPK/JNKs translocate to the nucleus and phosphorylate
      transcription factors, ultimately resulting in the modulation of gene expression.
      We have analyzed the activation of SAPK/JNK and stress-activated MAP3Ks using in
      vitro kinase assays. In addition, we have studied the role of different MAP3Ks in
      SAPK/JNK signaling by silencing specific MAP3K expression with RNAi and then
      analyzing the effect on activation of SAPK/JNKs and other MAPKs.

PMID- 20811977
TI  - Activation of p38 and determination of its activity.
AB  - The p38 mitogen-activated protein kinase (MAPK) pathway plays an important role
      in cellular responses to inflammatory stimuli and environmental stresses.
      Extracellular stimuli activate kinases upstream of p38, such as MKK3 and MKK6,
      which subsequently phosphorylate p38. p38 then participates in numerous
      biological processes by phosphorylating its downstream substrates. Here, our
      methodology mainly highlights how endogenous or exogenous p38 can be activated
      and its upstream kinases and downstream substrates identified.

PMID- 20811978
TI  - Activity assays for extracellular signal-regulated kinase 5.
AB  - Extracellular signal-regulated kinase 5 (ERK5) is also known as big MAPK (BMK1)
      or MAPK7. ERK5 is 115 kDa in mass and therefore larger than the other MAPKs such
      as ERK1/2, JNK, and p38. Like other MAPKs, ERK5 is ubiquitously expressed in
      mammalian cells and is part of a three kinase cascade involving a MAPK kinase
      (MEK5) and MAPK kinase kinase (primarily MEKK2 and MEKK3). ERK5 is important for
      proliferative responses to growth factors like epidermal growth factor and stress
      responses such as hyperosmolarity. Upon stimulation, ERK5 rapidly translocates to
      the nucleus for the control of transcription. ERK5 is also critical for
      maintenance of vascular integrity and endothelial cell survival. In this chapter,
      we define methods used to measure the activation of ERK5 using different
      biochemical and cell-based assays.

PMID- 20811979
TI  - Use of inhibitors in the study of MAP kinases.
AB  - The mitogen-activated protein (MAP) kinases are ubiquitous intracellular
      signaling proteins that respond to a variety of extracellular signals and
      regulate most cellular functions including proliferation, apoptosis, migration,
      differentiation, and secretion. The four major MAP kinase family members, which
      include the ERK1/2, JNK, p38, and ERK5 proteins, coordinate cellular responses by
      phosphorylating and regulating the activity of dozens of substrate proteins
      involved in transcription, translation, and changes in cellular architecture.
      Uncontrolled activation of the MAP kinases has been implicated in the initiation
      and progression of a variety of cancers and inflammatory disorders. As such, the
      ability to manipulate the activity of MAP kinase proteins with specific
      pharmacological inhibitors has received much attention as research tools for
      understanding basic mechanisms of cellular functions and for clinical tools to
      treat diseases. A variety of pharmacological inhibitors have been developed to
      selectively block MAP kinases directly or indirectly through targeting upstream
      regulators. This chapter will provide an overview of some of the current
      inhibitors that target MAP kinase signaling pathways and provide methodology on
      how to use selective MAP kinase inhibitors and immunoblotting techniques to
      monitor and quantify phosphorylation of MAP kinase substrates.

PMID- 20811980
TI  - MAP Kinase activation by receptor tyrosine kinases: in control of cell migration.
AB  - A myriad of cellular processes instigated by growth factors are mediated by cell
      surface-associated receptor tyrosine kinases (RTKs). Subsequent downstream
      activation of signaling cascades, as well as their crosstalk, endows specificity
      in terms of the phenotypic outcome, e.g., cellular proliferation, migration, or
      differentiation. Such signaling diversity is exemplified by the ability of the
      epidermal growth factor receptor (EGFR) to stimulate different MAPK cascades,
      especially the ERK1/2 cascade. It has been shown that the ability of the ERK1/2
      cascade to specify cell fate, such as cell migration, is dependent on signal
      duration governed by feedback control. Here we focus on one experimental system,
      MCF10A human mammary cells, and a phenotypic outcome of cell migration. We
      present methods to identify key components of underlying cascades and their
      effects on the migratory phenotype. We focus on profiling activation of signaling
      modules, as well as transcriptional regulation, emphasizing the high-throughput
      potential of such approaches.

PMID- 20811981
TI  - Activation of Ras and Rho GTPases and MAP Kinases by G-protein-coupled receptors.
AB  - A complex intracellular signaling network mediates the multiple biological
      activities of G-protein-coupled receptors (GPCRs). Among them, monomeric GTPases
      and a family of closely related proline-targeted serine-threonine kinases,
      collectively known as Mitogen-Activated Protein Kinases (MAPKs), appears to play
      central roles in orchestrating the proliferative responses to multiple mitogens
      that act on GPCRs. Upon GDP/GTP exchange, monomeric GTPases control the
      phosphorylation of conserved threonine and tyrosine residues in MAPKs by their
      immediate upstream kinases, increasing their enzymatic activity and inducing
      their translocation to the nucleus where they phosphorylate transcription
      factors, thereby regulating the expression of genes playing a key role in normal
      and aberrant cell growth. Recently, a number of GPCRs have been engineered to
      provide exclusive activation by synthetic drug-like compounds while becoming
      insensitive to endogenous ligands. These engineered receptors, named Receptors
      Activated Solely by Synthetic Ligands (RASSLs), promise better understanding of
      GPCRs signaling in vitro and in vivo, thus representing ideal tools to
      selectively modulate MAPK signaling routes controlling a wide range of biological
      functions, from proliferation to differentiation, migration, invasion, and cell
      survival or death by apoptosis.

PMID- 20811982
TI  - Regulation of MAP kinase signaling by calcium.
AB  - Mitogen-activated protein kinase (MAPK) signaling influences a variety of
      cellular responses, ranging from stimulation of cell proliferation to induction
      of senescence and/or apoptosis. Ca(2+) is a ubiquitous intracellular signaling
      molecule that controls multiple processes in cells. Published evidence has
      identified both direct and indirect interactions between the Ca(2+) and MAPK
      signaling pathways. Here, we describe assays to accurately determine the effect
      of changes in intracellular Ca(2+) concentration on MAPK activation.

PMID- 20811984
TI  - ERK-MAP Kinase signaling in the cytoplasm.
AB  - ERK-MAPK is activated by dual phosphorylation of its activation loop TEY motif by
      the MEK-MAPKK. ERK cytoplasmic activity should be measured by assaying both the
      level of dually phosphorylated ERK and the level of phosphorylated substrate. We
      describe two complementary methods for quantitatively measuring ERK activity
      toward the cytoplasmic p90 ribosomal S6 kinase (RSK). The first method is a
      straightforward immunoblot of endogenous ERK and RSK phosphoepitopes using
      phospho-specific antibodies. Infrared fluorescent secondary antibodies provide a
      linear readout that is quantitated using an Odyssey scanner (LI-COR). The second
      method is an immunoprecipitation of ERK followed by an in vitro immune complex
      kinase assay with purified GST-RSK as substrate. The level of ERK
      phosphotransferase activity, or (32)P-labeled phosphate transfer, is quantitated
      using a PhosphorImager.

PMID- 20811983
TI  - Identification of novel substrates of MAP Kinase cascades using bioengineered
      kinases that uniquely utilize analogs of ATP to phosphorylate substrates.
AB  - The Mitogen-Activated Protein Kinase (MAPK) family of signaling molecules
      regulates a number of cellular processes through the direct phosphorylation and
      regulation of a plethora of cellular proteins. Identifying the direct substrates
      of the MAPK pathway proteins is important for determining how the effects of MAPK
      activation have such profound effects on cell biology. In this chapter, we
      describe one method for specific labeling and identification of direct MAPK
      substrates. A single or double point mutation is generated within the ATP binding
      domain at a particular residue(s) termed the "gatekeeper" that comes into close
      contact with the N6 position of ATP. Most kinases contain an amino acid larger
      than alanine at this position. Mutation of the residue(s) to glycine or alanine
      generates a "pocket" that allows the mutant kinase to bind and uniquely utilize
      an analog of ATP that contains a chemical substituent at the N6 position. When
      radiolabeled analog is added to the mutant kinase and a complex mixture of
      cellular proteins, the only proteins that become radiolabeled are direct
      substrates of the mutant kinase. To label biologically relevant substrates, we
      take advantage of the direct binding of MAPKs to their substrates. An epitope
      tagged mutant kinase is expressed in cells and immunoprecipitated with associated
      substrates, which are then radiolabeled in an in vitro kinase reaction using
      (gamma-(32)P) ATP analog. Larger, unlabeled kinase reactions are run in parallel
      and used to identify the substrates by mass spectrometry.

PMID- 20811985
TI  - Lentiviral vectors to study the differential function of ERK1 and ERK2 MAP
      kinases.
AB  - Accumulating evidence indicates that p44(ERK1) and p42(ERK2) mitogen-activated
      protein kinases (MAPKs) have distinct quantitative roles in cell signaling. In
      our recently proposed model of regulation of ERK1 and ERK2, p42 plays a major
      role in delivering signals from the cell membrane to the nucleus, while p44 acts
      as a partial agonist of ERK2 toward effectors and downstream activators, thus
      providing a fine tuning system of the global signaling output. Here, we describe
      systems to modulate MAPK signaling in vitro and in vivo via lentiviral vector
      (LV)-mediated gene transfer, using three systems: RNAi with small hairpin RNAs,
      microRNA-mediated gene knockdown, and expression of signaling-interfering mutants
      of MEK1. We show, by using proliferation assays in mouse embryo fibroblasts (MEF)
      and NIH 3T3 cells, that gene knockdown of ERK1 promotes cell proliferation in a
      manner indistinguishable from a constitutively active MEK1 construct, while ERK2
      RNAi causes a significant growth arrest, similar to that observed with the
      ectopic expression of a dominant negative MEK1 mutant.

PMID- 20811986
TI  - Structural studies of MAP Kinase cascade components.
AB  - MAPK cascade components have been the subject of structural analysis, advancing
      our understanding of how these enzymes are activated and how they interact. A
      surprising finding has been that unique inactive conformers are adopted by many
      of these kinases. These inactive conformers are interesting and often require
      experimental phases to determine their crystal structures because molecular
      replacement techniques are not successful. Here, we describe the preparation of
      MAP2K MEK6 and MAP3K TAO2 substituted with selenomethionine (SeMet) for de novo
      phasing. TAO2 and SeMet TAO2 were expressed in insect cells.

PMID- 20811987
TI  - Analysis of MAP kinases by hydrogen exchange mass spectrometry.
AB  - Hydrogen exchange mass spectrometry (HX-MS) is an experimental technique that can
      be used to -examine solvent accessibility and conformational mobility in
      biological macromolecules. This chapter summarizes studies using HX-MS to examine
      the regulation of conformation, protein mobility, and ligand binding to MAP
      kinases. We describe the planning and design of HX-MS experiments, strategies for
      data analysis and interpretation, and available software.

PMID- 20811988
TI  - A "molecular evolution" approach for isolation of intrinsically active (MEK
      independent) MAP kinases.
AB  - Mitogen-activated protein (MAP) kinases are a large family of enzymes composed of
      about four subfamilies, each containing several isoforms and splicing variants.
      Many MAP kinases are coexpressed in each eukaryotic cell and coactivated in
      response to various stimuli. It is, therefore, difficult to explore the specific
      downstream effects of each species of MAPK. Expression of an intrinsically active
      variant of a MAPK, while other MAPKs are not active, allows for tracking of a
      specific array of substrates, target genes, and biological/pathological effects
      corresponding to the expressed molecule. This chapter describes a method for
      obtaining such intrinsically active MAPKs. Because of the unique mode of MAPK
      activation, which is absolutely dependent on unconventional phosphorylation (on
      neighboring Thr + Tyr residues), a rational design of mutations that would render
      the kinase intrinsically active is currently unfeasible. Our method is based,
      therefore, on a "Molecular Evolution" approach that uses the power of yeast
      genetics and is unbiased toward the mutation sites. We describe in detail how to
      prepare a large population of randomly mutated molecules of the desired MAPK and
      how to screen this library in a yeast strain lacking the relevant MAPK kinase
      (MAPKK). The idea is to identify MAPK variants that are fulfilling all MAPK
      functions and allow growth of this strain - namely, MAPK molecules that function
      biologically in the complete absence of their upstream activator. We further
      describe the details of the "plasmid-loss" assay used for distinguishing between
      true positive and false positive clones. Finally, we report on a new yeast strain
      lacking four MAPKKs that could serve as a universal target for screening for
      active MAPK of all subfamilies.

PMID- 20811989
TI  - Reconstitution of the nuclear transport of the MAP kinase ERK2.
AB  - The nuclear-cytoplasmic distribution of ERK2 is regulated in response to various
      stimuli and changes in cell context. Furthermore, the nuclear flux of ERK2 occurs
      by several energy- and carrier-dependent and -independent mechanisms. ERK2 has
      been shown to translocate into and out of the nucleus by facilitated diffusion
      through the nuclear pore, interacting directly with proteins within the nuclear
      pore complex, as well as by karyopherin-mediated transport. Nuclear export has
      been suggested to be CRM1- and MEK1/2-dependent. Here, we describe a general
      nuclear import assay of wild-type ERK2 that can be employed to identify different
      mechanisms governing nuclear entry of the protein kinase, adapted to evaluate
      ERK2 mutants that impair nuclear entry to dissect energy- and carrier-dependent
      and -independent mechanisms, and extended to characterize export mechanisms.

PMID- 20811990
TI  - Localization and trafficking of fluorescently tagged ERK1 and ERK2.
AB  - The action of ERK1 and ERK2 activity on the nuclear substrates requires crossing
      the nuclear envelope and the localization of phospho-ERK into the nucleus. The
      nucleo-cytoplasmic trafficking of ERK is therefore crucial for the correct
      functioning of the pathway. Indeed, this step is necessary for the correct
      control of gene expression by growth-factors, for morphological transformation of
      fibroblasts and for neurite extension in PC12. Furthermore, disruption of ERK2
      localization in the nucleus severely affects the transduction of ERK2 signaling.
      This process has now been observed and quantitatively measured by expressing
      fluorescently tagged ERK1 and ERK2. These experiments provide important insight
      on the operation of these signaling modules and have revealed an hitherto unknown
      functional difference between ERK1 and ERK2.

PMID- 20811991
TI  - Studying the regulation of MAP Kinase by MAP Kinase phosphatases in vitro and in
      cell systems.
AB  - Signaling through MAPK pathways involves a network of activating kinases and
      inactivating phosphatases. While single MAPK kinases account for specific
      activation of the distinct MAPKs, inactivation of MAPKs by phosphatases involves
      a wider spectrum of enzymes, with phosphatases from distinct families displaying
      specificity toward MAPKs. The dual-specificity family of MAPK phosphatases, MKPs,
      constitutes the major group of MAPK inactivating phosphatases. MKPs are widely
      expressed, in a tissue- and development-regulated manner, and the control of
      their expression and function is crucial for the regulation of MAPK signaling.
      Here, we present three methods to analyze the regulation of MAPKs by MKPs, using
      transient and stable-inducible MKP overexpression cell systems and in vitro
      phosphatase experiments.

PMID- 20811992
TI  - Proteomic analysis of scaffold proteins in the ERK cascade.
AB  - ERK cascade scaffolds serve as docking platforms to coordinate the assembly of
      multiprotein complexes that contribute to the spatial and temporal control of ERK
      signaling. Given that protein-protein interactions are essential for scaffold
      function, determining the full repertoire of scaffold binding partners will
      likely provide new insight into the regulation and activities of the ERK cascade
      scaffolds. In this chapter, we describe methods to identify scaffold interacting
      proteins using a proteomics approach. This protocol is based on the affinity
      purification of scaffold complexes from tissue culture cells and utilizes mass
      spectrometry to identify the protein constituents of the complex.

PMID- 20811993
TI  - Analysis of ERKs' dimerization by electrophoresis.
AB  - Signals transmitted by ERK MAP Kinases regulate the functions of multiple
      substrates present in the nucleus and the cytoplasm. Once phosphorylated, ERKs
      dimerize. The functions of these dimers had remained elusive until recently when
      we demonstrated that ERK dimers are assembled using scaffolds proteins as
      platforms. Dimerization is critical for connecting the scaffolded ERK complex to
      cognate cytoplasmic substrates. Contrarily, nuclear substrates associate to ERK
      monomers. These results identify dimerization as a key determinant of the spatial
      specificity of ERK signals. Moreover, we showed that preventing ERK dimerization,
      without affecting ERK phosphorylation, is sufficient for attenuating cellular
      proliferation, transformation, and tumor development. Thus, analyzing ERK
      dimerization will be an important factor in the future for determining, for
      example, the real impact on the ERK pathway of some drugs that do not affect ERK
      phosphorylation. Herein, we describe user-friendly methods for such purpose.

PMID- 20811994
TI  - MAP Kinase: SUMO pathway interactions.
AB  - The convergence and coordinated cross talk of different signalling pathways forms
      a regulatory network which determines the biological outcome to environmental
      cues. The MAPK pathways are one of the important routes by which extracellular
      signals are transduced into intracellular responses. Through protein
      phosphorylation mechanisms, they can play a pivotal role in regulating other
      posttranslational modifications such as protein acetylation and ubiquitination.
      In addition, protein sumoylation has emerged as an important pathway which also
      functions through post-translational modification. The SUMO pathway modulates a
      diverse range of cellular processes including signal transduction, chromosome
      integrity, and transcription. Interestingly, recent studies have provided links
      between the SUMO and MAPK signalling pathways which converge to modulate
      transcription factor activity. This was first demonstrated by the observation
      that the activation of the ERK pathway caused de-sumoylation of the transcription
      factor, Elk-1. Furthermore, a growing number of links are now being made between
      the MAPK pathway and protein sumoylation. Given the nature of protein sumoylation
      in diverse biological functions, it is not surprising that the effect of MAPK
      pathways on sumoylation varies between different proteins. Here, we describe
      protocols that can be used in studying the cross talk between the MAPK and SUMO
      pathways, particularly at the level of gene regulation.

PMID- 20811995
TI  - Computational modelling of kinase signalling cascades.
AB  - In this chapter, we describe general methods used to create dynamic computational
      models of kinase signalling cascades, and tools to support this activity. We
      focus on the ordinary differential equation models, and show how these fit into a
      general framework of qualitative and quantitative (stochastic and continuous)
      models. The modelling we describe is part of the activity of BioModel engineering
      which provides a systematic approach for designing, constructing, and analyzing
      computational models of biological systems.

PMID- 20811996
TI  - Analysis of mitogen-activated protein kinase activity in yeast.
AB  - Mitogen-activated protein (MAP) kinases play central roles in transmitting
      extracellular and intracellular information in a wide variety of situations in
      eukaryotic cells. Their activities are perturbed in a large number of diseases,
      and their activating kinases are currently therapeutic targets in cancer. MAPKs
      are highly conserved among all eukaryotes. MAPKs were first cloned from the yeast
      Saccharomyces cerevisiae. Yeast has five MAPKs and one MAPK-like kinase. The
      mating MAPK Fus3 is the best characterized yeast MAPK. Members of all subfamilies
      of human MAPKs can functionally substitute S. cerevisiae MAPKs, providing systems
      to use genetic approaches to study the functions of either yeast or human MAPKs
      and to identify functionally relevant amino acid residues that enhance or reduce
      the effects of therapeutically relevant inhibitors and regulatory proteins. Here,
      we describe an assay to measure Fus3 activity in immune complexes prepared from
      S. cerevisiae extracts. The assay conditions are applicable to other MAPKs, as
      well.

PMID- 20811997
TI  - Detection of RTK pathway activation in Drosophila using anti-dpERK
      immunofluorescence staining.
AB  - In Drosophila, like in other metazoans, receptor tyrosine kinase (RTK) signaling
      pathways control diverse cellular processes such as migration, growth, fate
      determination, and differentiation (Shilo, Development 132:4017-4027, 2005).
      Activation of RTKs by their extracellular ligands triggers a signal transduction
      cascade, mediated by the Ras/Raf/MEK cassette, which ultimately leads to dual
      phosphorylation and activation of the mitogen-activated protein
      kinase/extracellularly regulated kinase (MAPK/Erk). Once active, MAPK/Erk
      phosphorylates its cytoplasmic and nuclear substrates, consequently modulating
      (i.e., stimulating or inhibiting) their biological function (Murphy and Blenis,
      Trends in Biochemical Sciences 31:268-275, 2006). The currently available
      antibody specific for the doubly phosphorylated form of MAPK/Erk (dpERK) (Yung et
      al., FEBS Letters 408:292-296, 1997) provides a valuable readout for RTK
      signaling: it enables the spatiotemporal detection of RTK pathway activity in the
      developing organism, in situ (Gabay et al., Development 124:3535-3541, 1997;
      Gabay et al., Science 277:1103-1106, 1997). Here, we present a detailed protocol
      for anti-dpERK immunofluorescent staining that can be applied to the analysis of
      MAPK/Erk signaling in Drosophila embryogenesis.

PMID- 20811998
TI  - Studying MAP Kinase pathways during early development of Xenopus laevis.
AB  - The following chapter describes several methods involved in the detection of MAPK
      activities and phosphorylated proteins during early development of Xenopus
      laevis. The Xenopus embryo provides a powerful platform for biochemical studies.
      We describe here basic methods of embryo manipulations such as egg fertilization,
      embryo growth and maintenance, microinjection of capped RNA and antisense
      morpholino oligonucleotides (AMOs), and isolation of explants. In addition, we
      describe methods to detect phosphorylated proteins, to analyze kinase activity,
      and to interfere with signaling pathways. Immunohistochemical staining performed
      on whole embryos or on tissue sections is an additional method for the detection
      of phosphorylated proteins in the developing embryo. Approaches to activate or
      inhibit MAPK activities including the ectopic expression of mutated isoforms of
      MAPK kinase, or the incubation of embryo explants with pharmacological inhibitors
      are described. Finally, we describe an in vitro kinase assay specifically
      designed for the Xenopus embryo.

PMID- 20811999
TI  - Deciphering signaling pathways in vivo: the Ras/Raf/MEK/ERK cascade.
AB  - The Ras/Raf/MEK/ERK cascade is a highly conserved signal transduction module,
      whose activation results in a number of different physiological outcomes.
      Depending on the cell type or the stimulus used, the pathway has been implicated
      in proliferation, differentiation, apoptosis, and migration. Because of this wide
      range of activities, these kinases are considered attractive (anticancer)
      therapeutic targets. However, their essential functions in the context of the
      whole organism are still incompletely known. Here, we describe
      immunohistochemical and immunofluorescence methods that can be used to define the
      essential function(s) and the relevant downstream targets of Raf-1, B-Raf, and
      Mek-1 in in vivo models of organ development, remodeling, and neoplasia.

PMID- 20812000
TI  - Mutational and functional analysis in human Ras/MAP kinase genetic syndromes.
AB  - The Ras/mitogen-activated protein kinase (MAPK) pathway is essential in
      regulation of the cell cycle, cell differentiation, growth, and cell senescence,
      each of which are critical to normal development. A class of developmental
      disorders, the "RASopathies," is caused by germline mutations in genes that
      encode protein components of the Ras/MAPK pathway which result in dysregulation
      of the pathway and profound deleterious effects on development. One of these
      syndromes, cardiofaciocutaneous (CFC) syndrome, is caused by germline mutations
      in BRAF, MAP2K1 (MEK1) and MAP2K2 (MEK2), and possibly KRAS genes. Here, we
      describe the laboratory protocols and methods that we used to identify mutations
      in BRAF and MEK1/2 genes as causative for CFC syndrome. In addition, we present
      the techniques used to determine the effect these mutations have on activity of
      the Ras/MAPK pathway through Western blot analysis of the phosphorylation of
      endogenous ERK1/2, as well as through the use of an in vitro kinase assay that
      measures the phosphorylation of Elk-1.

PMID- 20812001
TI  - Implication of the ERK pathway on the post-transcriptional regulation of VEGF
      mRNA stability.
AB  - Vascular Endothelial Growth Factor-A (VEGF-A) is one of the most important
      regulators of physiological and pathological angiogenesis. Constitutive
      activation of the ERK pathway and over-expression of VEGF-A are common
      denominators of tumours of different origins. Understanding VEGF-A regulation is
      of primary importance to better comprehend pathological angiogenesis. VEGF-A
      expression is regulated at all steps of its synthesis including transcription,
      mRNA stability, an under estimated way of VEGF regulation and translation. In
      this chapter, we present the link between VEGF mRNA stability through AU-rich
      sequences present in its 3'-untranslated region (3'-UTR) and the ERK pathway. We
      present several methods that have been used to demonstrate that ERKs increase
      VEGF mRNA half-life. This mRNA-stabilising effect is partly due to reduction of
      the mRNA destabilising effects of Tristetraprolin (TTP), an AU-Rich binding
      protein which binds to VEGF-A mRNA 3'-UTR.

PMID- 20812002
TI  - Studies on MAP Kinase signaling in the immune system.
AB  - The primary function of the immune system is to protect the organism from
      invading pathogens. In response to pathogen invasion, multiple signaling pathways
      are activated in immune cells, leading to diverse immune defense mechanisms.
      Chief among these pathways is the activation of MAPKs, which are crucial for
      transcriptional and nontranscriptional responses of the immune system. Here we
      describe protocols to study the roles of MAPKs in T lymphocytes, a cell type
      central for immune regulation. Specifically, we describe flow cytometry-based
      assays to analyze the roles of MAPKs in the development, homeostasis,
      proliferation, and apoptosis of murine T cells. We also describe methods to
      examine the activation of MAPKs in T cells.

PMID- 20812003
TI  - Methods to study MAP kinase signalling in the central nervous system.
AB  - The mitogen-activated protein kinase (MAPK) family of intracellular signal
      transducers includes ERK1/2, ERK5, JNK/SAPK, and p38 and has been shown to
      control survival, proliferation and differentiation of cells composing the
      central and peripheral nervous system. Some MAPKs preferably induce the
      differentiation of neural precursor cells into the neuronal lineage, whereas
      others into the glial lineages, which comprises astrocytes, oligodendrocytes, and
      Schwann cells. MAPKs and their upstream signalling receptors play also an
      important role in the development of neurodegenerative diseases due to their
      capacity to control neural cell apoptosis. It is therefore of vital importance to
      better define the processes controlled by MAPKs to design therapies aimed at
      preventing neurodegenerative disorders in the future. The methods described in
      this chapter about how to culture and analyse primary astrocytes and neurons in
      culture have allowed us to improve our understanding on the role of the EGFR and
      its downstream signalling pathways in neural cell development and
      neurodegeneration.

PMID- 20812004
TI  - MAP kinase regulation of the mitotic spindle checkpoint.
AB  - Maintaining the integrity of the cell cycle is critical for ensuring that cells
      only undergo DNA replication and proliferation under controlled conditions in
      response to discrete stimuli. One mechanism by which the fidelity of this process
      is guaranteed is through the activation of cell cycle checkpoints. The mitotic
      spindle checkpoint, which is regulated by Aurora B kinase, ensures proper
      kinetochore attachment to chromosomes leading to equal distribution of
      chromosomes to daughter cells. We demonstrated that the mitogen-activated protein
      kinase (MAPK) cascade regulates mitotic progression and the spindle checkpoint.
      As demonstrated by immunofluorescence at kinetochores, depletion of Raf Kinase
      Inhibitory Protein (RKIP), an inhibitor of Raf/MEK/ERK signaling, causes an
      increase in MAPK activity that inhibits Aurora B kinase activity. By monitoring
      mitotic index and transit time from nuclear envelope breakdown to anaphase, we
      demonstrated that RKIP depletion leads to a defective spindle checkpoint and
      genomic instability, particularly in response to drugs that disrupt microtubule
      function.

PMID- 20812005
TI  - Using high-content microscopy to study gonadotrophin-releasing hormone regulation
      of ERK.
AB  - Gonadotrophin-releasing hormone (GnRH) is a hypothalamic peptide that acts via
      G(q/11)-coupled 7TM receptors on pituitary gonadotrophs and mediates the central
      control of reproduction. Recent evidence also indicates that GnRH can affect
      numerous tissues, but the molecular mechanisms of GnRH receptor stimulation are
      cell type-specific. Extracellular signal-regulated kinase (ERK) 1 and 2 are key
      regulators of GnRH function in several cell types, but they also integrate
      signals from a wide variety of other stimuli. This leads to the obvious question
      of how specific cellular responses to ERK activation occur, and it is now clear
      that this is, in part, achieved through strict spatiotemporal control of ERK
      activity. This means that, in order to infer the function of ERK regulation
      accurately, multiple readouts for ERK activity, localisation and downstream
      consequences (e.g. transcriptional activation or cell growth) must be compared
      simultaneously. Here, we describe some of our findings in the investigation of
      GnRH signalling to ERK, with particular emphasis on novel, high-content
      microscopy methods for studying ERK regulation.

PMID- 20812006
TI  - Evidence for a psychotic posttraumatic stress disorder subtype based on the
      National Comorbidity Survey.
AB  - PURPOSE: This study assessed the distribution of posttraumatic stress disorder
      (PTSD) symptoms and psychosis indicators among a large sample of individuals with
      a lifetime diagnosis of PTSD. The identification of a psychotic PTSD subtype was
      also predicted. METHOD: Using data from the National Comorbidity Survey a latent
      class analysis was conducted on the PTSD symptoms of intrusion, avoidance, and
      hyperarousal and the psychosis hallucination and delusion indicators. RESULTS:
      Results indicated four latent classes, two of which had relatively high
      probabilities of endorsing the hallucination and delusion indicators. These
      classes were associated with a broad range of traumatic experiences. One
      particular class had high probabilities of endorsing both the psychosis
      indicators and the PTSD symptoms and was associated with a broad range of
      comorbid psychiatric disorders. CONCLUSION: There was a candidate class that met
      the characteristics expected to be evident in a psychotic PTSD subtype.

PMID- 20812007
TI  - Plasma osteoprotegerin, arterial stiffness, and mortality in normoalbuminemic
      Japanese hemodialysis patients.
AB  - A high circulating osteoprotegerin (OPG) level may be a risk factor for vascular
      calcification and mortality in hemodialysis patients. OPG and pulse wave velocity
      (PWV) were measured at baseline in 151 normoalbuminemic, long-term (>3 years)
      Japanese hemodialysis patients who were prospectively followed for 6 years. In
      long-term normoalbuminemic Japanese hemodialysis patients, OPG levels were
      strongly linked with both arterial stiffness and worse outcome. INTRODUCTION: A
      high circulating OPG level is reported to be a risk factor for vascular
      calcification and mortality in Western chronic kidney disease (CKD) patients but
      it is not known if this is true for Japanese CKD patients, where a different risk
      profile may operate. METHODS: OPG and PWV were measured at baseline in 151
      normoalbuminemic, long-term (>3 years) Japanese hemodialysis patients (median age
      62 years) who were prospectively followed for 6 years. RESULTS: OPG levels were
      associated in multivariate analysis with age, dialysis vintage, history of
      cardiovascular disease (CVD) and parathyroid hormone levels. C-reactive protein
      levels did not correlate with OPG. Patients with clinical history of CVD had
      significantly higher OPG levels and OPG levels were positively correlated to PWV,
      an index of arterial stiffness. These associations were independent of age, sex,
      dialysis vintage, and diabetes. During the follow-up period, 40 deaths, including
      25 cardiovascular deaths, were recorded. In crude analysis, each unit of increase
      in OPG was associated with increased all-cause (hazard ratios 1.14, 95%
      confidence interval 1.08-1.20) and CVD mortality (1.14 [1.07-1.21]), which
      persisted after adjustment for age, sex, dialysis vintage, diabetes, and baseline
      CVD (1.12 [1.05-1.19] and 1.11 [1.02-1.19], all-cause and CVD mortality,
      respectively). CONCLUSIONS: In long-term normoalbuminemic Japanese hemodialysis
      patients, with low prevalence of inflammation, OPG levels were strongly linked
      with both arterial stiffness and worse outcome.

PMID- 20812008
TI  - How strontium ranelate, via opposite effects on bone resorption and formation,
      prevents osteoporosis.
AB  - Oestrogen deficiency increases the rate of bone remodelling which, in association
      with a negative remodelling balance (resorption exceeding formation), results in
      impaired bone architecture, mass and strength. Current anti-osteoporotic drugs
      act on bone remodelling by inhibiting bone resorption or by promoting its
      formation. An alternative therapeutic approach is based on the concept of
      inducing opposite effects on bone resorption and formation. One therapeutic
      agent, strontium ranelate, was shown to induce opposite effects on bone
      resorption and formation in pre-clinical studies and to reduce fracture risk in
      postmenopausal osteoporotic patients. How strontium ranelate acts to improve bone
      strength in humans remains a matter of debate, however. This review of the most
      recent pre-clinical and clinical studies is a critical analysis of strontium
      ranelate's action on bone resorption and formation and how it increases bone
      mass, microarchitecture and strength in postmenopausal osteoporotic women.

PMID- 20812009
TI  - Rivaroxaban versus enoxaparin for thromboprophylaxis after total hip or knee
      arthroplasty: a meta-analysis of randomized controlled trials.
AB  - PURPOSE: Rivaroxaban is a newly developed oral medicine that direct inhibits
      factor Xa for the prevention and treatment of thromboembolic disorders. The
      objective of this study was to compare the efficacy and safety of rivaroxaban
      versus enoxaparin, a medicine routinely used for thromboprophylaxis after total
      hip or knee arthroplasty. METHODS: We performed a meta-analysis of relevant
      randomized controlled trials (RCTs) identified in PubMed, Cochrane library, and
      Embase. The primary efficacy outcome for our meta-analysis was total venous
      thromboembolism (VTE) and all-cause mortality. The primary safety outcome was
      bleeding events, which were categorized as major, clinically relevant non-major,
      or minor events. RESULTS: Eight RCTs, involving 15,586 patients, were included in
      our meta-analysis. Compared to enoxaparin, thromboprophylaxis with rivaroxaban
      was associated with significantly fewer VTE and all-cause mortality [9,244
      patients, risk ratio (RR) 0.56, 95% confidence interval (CI) 0.39-0.80] cases and
      a similar incidence of bleeding cases (major bleeding events: 13,384 patients, RR
      1.65, 95% CI 0.93-2.93; clinically relevant non-major bleeding events: 13,384
      patients, RR 1.21, 95% CI 0.98-1.50; total bleeding events, 13,384 patients, RR
      1.10, 95% CI 0.97-1.24). The total hip or knee arthroplasty subgroup analysis
      revealed consistent efficacy and safety findings. CONCLUSIONS: Rivaroxaban was
      more effective than the recommended dose of enoxaparin and had a similar safety
      profile for thromboprophylaxis after hip and knee arthroplasty.

PMID- 20812010
TI  - Simian immunodeficiency virus-specific CD4+ T cells from successful vaccinees
      target the SIV Gag capsid.
AB  - We recently demonstrated that vaccinated rhesus macaques controlled viral
      replication of a heterologous SIV challenge. Here, we analyzed anamnestic SIV
      specific CD4+ T-cell responses expanding immediately after challenge and show
      that successful vaccinees consistently targeted a short region of the Gag-p27
      Capsid (amino acids 249-291). We have also defined the major histocompatibility
      complex class II (MHC-II) restricting alleles for several of these responses and
      show that DQ-restricted CD4+ T-cells depend on unique combinations of both the
      DQA and DQB alleles. Analysis of SIV-specific CD4+ T-cell responses elicited by a
      successful vaccine may have important implications in the understanding of
      vaccine design.

PMID- 20812011
TI  - Emergy assessment of a wheat-maize rotation system with different water
      assignments in the north China plain.
AB  - Sustainable water use is seriously compromised in the North China Plain (NCP) due
      to the huge water requirements of agriculture, the largest use of water
      resources. An integrated approach which combines the ecosystem model with emergy
      analysis is presented to determine the optimum quantity of irrigation for
      sustainable development in irrigated cropping systems. Since the traditional
      emergy method pays little attention to the dynamic interaction among components
      of the ecological system and dynamic emergy accounting is in its infancy, it is
      hard to evaluate the cropping system in hypothetical situations or in response to
      specific changes. In order to solve this problem, an ecosystem model (Vegetation
      Interface Processes (VIP) model) is introduced for emergy analysis to describe
      the production processes. Some raw data, collected by investigating or observing
      in conventional emergy analysis, may be calculated by the VIP model in the new
      approach. To demonstrate the advantage of this new approach, we use it to assess
      the wheat-maize rotation cropping system at different irrigation levels and
      derive the optimum quantity of irrigation according to the index of ecosystem
      sustainable development in NCP. The results show, the optimum quantity of
      irrigation in this region should be 240-330 mm per year in the wheat system and
      no irrigation in the maize system, because with this quantity of irrigation the
      rotation crop system reveals: best efficiency in energy transformation
      (transformity = 6.05E + 4 sej/J); highest sustainability (renewability = 25%);
      lowest environmental impact (environmental loading ratio = 3.5) and the greatest
      sustainability index (Emergy Sustainability Index = 0.47) compared with the
      system in other irrigation amounts. This study demonstrates that application of
      the new approach is broader than the conventional emergy analysis and the new
      approach is helpful in optimizing resources allocation, resource-savings and
      maintaining agricultural sustainability.

PMID- 20812012
TI  - [High-throughput sequencing of frozen and paraffin-embedded tumor and normal
      tissue].
AB  - Until now high-throughput sequencing of tumor samples relied on DNA isolated from
      fresh frozen tissues, the preparation of which, however, is relatively laborious.
      The use of preserved material, i.e. from tissue banks, could help to avoid this
      limitation and would enable the reanalysis of diverse clinical trials. So far we
      have shown that formalin-fixed paraffin-embedded (FFPE) tissue samples can be
      used for genomic re-sequencing processes. FFPE samples are amply available from
      surgical tumor resections and histopathological diagnosis, and comprise tissue
      from precursor lesions, primary tumors, and lymphogenic and/or hematogenic
      metastases. To generate models which predict the response to therapy, FFPE tissue
      also has the advantage that it is available from a variety of clinical trials.
      Second generation sequencing techniques are not only applicable to snap frozen
      and FFPE tissues for whole genome analyses but also for targeted resequencing
      approaches. In addition, the detection of copy number variations and mutations in
      FFPE tissues can be obtained within one sequencing run. The possibility of using
      genome-wide technologies irrespective of the mode of storage facilitates the
      retrieval of useful material and is a prerequisite for subsequent computational
      modelling approaches.

PMID- 20812013
TI  - [cFLIP diminishes CD95-induced apoptosis of CD30-stimulated cutaneous anaplastic
      large T cell lymphoma (cALCL) cells].
AB  - Stimulation of the TNF receptors CD30 and CD95 exerts opposite effects. Crosstalk
      of both receptors is unknown. We aimed to reveal regulatory mechanisms of CD30
      induced effects on CD95 signaling of cALCL cell lines. "CD30/CD95 crosstalk
      analysis" was performed in cALCL cell lines by comparison of CD30 or CD95
      stimulation and CD30/CD95 costimulation. Receptor expression and induction of
      apoptosis was investigated by flow cytometry. mRNA expression of CD30-inducible
      genes (cFLIP, TRAF1, cIAP2, and A20) was compared by semiquantitative reverse
      transcription (RT-RQ-) PCR in stimulated and unstimulated cells. Protein
      expression of IkappaBalpha, p100/p52, caspase-8, caspase-3, and cFLIP was
      analyzed by immunoblotting. A lentiviral-based shRNA-mediated approach was used
      to inhibit cFLIP expression. CD30/CD95 crosstalk experiments revealed that CD30
      ligation leads to NFkappaB-mediated cFLIP upregulation in cALCL cells, which in
      turn enhanced resistance to CD95-mediated apoptosis. This effect is based on the
      CD30-induced upregulation of cFLIP. Knockdown of cFLIP restores sensitivity to
      CD95-mediated apoptosis. We conclude that the anti-apoptotic function of CD30
      antibodies should be kept in mind if CD30 antibody-based therapeutic concepts for
      ALCL lymphoma are considered.

PMID- 20812014
TI  - [Immunohistochemical evaluation of somatostatin receptor subtypes in surgical
      pathology specimens of neuroendocrine tumors].
AB  - The clinical development of specific/selective or more potent analogues of
      somatostatin has made the evaluation of somatostatin receptor subtypes in
      archival specimens or 10% formalin-fixed and paraffin-embedded specimens of
      neuroendocrine tumor (NET) critical to conferring the maximum clinical benefits
      on NET patients. Immunohistochemistry of somatostatin receptor subtypes could
      contribute to profiling their expression patterns in these patients. Therefore,
      surgical pathologists are expected to be asked to immunostain and evaluate
      somatostatin receptor subtypes in NET specimens in the near future by clinicians.
      However, there are problems associated with immunohistochemistry of somatostatin
      receptor subtypes, in particular with their evaluation and interpretation.
      Therefore, both pathologists and clinicians involved in the care or management of
      NET patients should be aware of the advantages and limitations of
      immunohistochemical evaluation of somatostatin receptor subtypes in order to
      achieve the most efficient treatment outcome for patients.

PMID- 20812015
TI  - New trends in minimally invasive urological surgery: what is beyond the robot?
AB  - PURPOSE: To review the minimal-invasive development of surgical technique in
      urology focusing on nomenclature, history and outcomes of Laparo-Endoscopic
      Single-site Surgery (LESS), Natural Orifice Translumenal Endoscopic Surgery
      (NOTES) and Computer-Assisted Surgery (CAS). METHODS: A comprehensive literature
      search was conducted in order to find article related to LESS, NOTES and CAS in
      urology. The most relevant papers over the last 10 years were selected in base to
      the experience from the panel of experts, journal, authorship and/or content.
      RESULTS: Seven hundred and fifty manuscripts were found. Papers on LESS describe
      feasibility/safety in most of the procedures with a clinical experience of more
      than 300 cases and five compared results to standard laparoscopy without showing
      significant differences. NOTES accesses have been proved their feasibility/safety
      in experimental study. In human, the only procedures performed are on kidney and
      through a hybrid-Transvaginal route. New robots overcome the main drawbacks of
      the DaVinci(r) platform. The use of CAS is increasing its popularity in urology.
      CONCLUSIONS: LESS has been applied in clinical practice, but only ongoing
      technical and instrumental refinement will define its future role and overall
      benefit. The transition to a clinical application of NOTES seems at present only
      possible with multiple NOTES access and transvaginal access. Robot and Soft
      Tissue Navigation appear to be important to improve surgical skills. We are
      already witness to the advantages offered by the former even if costs need to be
      redefined based on pending long-term results. The latter will probably upgrade
      the quality of surgery in a near future.

PMID- 20812016
TI  - The presence of ochratoxin A in cord serum and in human milk and its
      correspondence with maternal dietary habits.
AB  - BACKGROUND: Ochratoxin A (OTA) is a mycotoxin present in food that can be found
      in human blood and milk. PURPOSE: The link between the nutritional habits of
      pregnant women both of Italian and foreign nationality resident in Italy and the
      presence of ochratoxin A in cord blood and in maternal milk was investigated.
      METHODS: The study involved 130 pregnant women. Food consumption during pregnancy
      was evaluated by means of the EPIC questionnaire; OTA content was determined in
      cord serum and maternal milk by HPLC. RESULTS: The mean daily dietary intake of
      OTA was 1.02 +/- 1.20 and 0.87 +/- 0.78 ng/kg of bodyweight for Italian and non
      Italian women, respectively, but this difference was not statistically
      significant. The incidence of positive milk samples was 73.0 and 85.0% among the
      Italian and non-Italian mothers, respectively. Pork meat, soft drinks, sweets and
      red wine showed a significant relationship with OTA level in serum. As far as
      milk is concerned, a positive relationship resulted for pork meat, sweets, soft
      drinks and seed oils. A positive relationship between serum OTA level and the
      ratio serum/milk OTA was found. The intake of OTA had no effect on the cord blood
      creatinine level. CONCLUSIONS: This study confirms that OTA is widely present in
      human milk and therefore could pose a risk for the newborn.

PMID- 20812017
TI  - Effect of acute cold exposure on lung perfusion and tracheal smooth muscle
      contraction in rabbit.
AB  - Acute exposure to cold temperature can affect the respiratory system of those
      exposed to extreme weather and induces asthma in asthmatic patients. However, the
      effect on lung perfusion and the pulmonary circulation was not addressed in any
      previous study. The present study investigates the effects of acute cold exposure
      on tracheal smooth muscle and lung perfusion. New Zealand White rabbits were used
      in these experiments. For in vitro experiments, isolated tracheal segments were
      suspended in organ baths containing Krebs' solution for isometric tension
      recording. Tissue response to cooling from 37 to 4 degrees C was examined. For in
      vivo experiments, the rabbits were kept in a cold room (4 degrees C) for 1 h.
      Lung perfusion scintigraphy was performed at the end of this period. Each rabbit
      was injected with 74 MBq (2 mCi) technetium-99m macroaggregated ((99m)Tc MAA).
      Perfusion studies were done by using Gamma camera equipped with a low-energy,
      high-resolution, parallel-hole collimator interfaced with a computer. Static
      images were acquired 5 min after administration of the radiotracer. Cooling
      induced a rapid and reproducible contraction in the tracheal smooth muscle.
      Rabbits exposed to cold temperature had lesser lung perfusion than controls using
      radionuclide perfusion study. Our results highlight the response of tracheal
      muscle and pulmonary circulation to cold exposure. These results indicate that
      cooling induced contraction of the trachea and decreased pulmonary circulation
      and lung perfusion. This summation of acute cooling for tracheal smooth muscle
      and pulmonary circulation seems to be the reason for the severe cooling-induced
      contraction.

PMID- 20812018
TI  - Increased neuroendocrine cells in resected metastases compared to primary
      colorectal adenocarcinomas.
AB  - Neuroendocrine differentiation has been described in rectal adenocarcinomas
      receiving neoadjuvant therapy prior to radical surgery, but its clinical
      relevance is controversial and no data are currently available in colorectal
      carcinoma metastases as compared to primary tumors. The presence of chromogranin
      A positive tumor cells was investigated by means of immunohistochemistry on
      surgical specimens from 54 primary colorectal carcinomas and their corresponding
      metastases, resected at diagnosis or during tumor progression. In 47 patients,
      tumor metastases were resected 1 month to 12 years after chemotherapy and/or
      radiotherapy, while in the remaining seven patients no additional therapy after
      primary surgery was performed. In primary tumors, neuroendocrine differentiation
      was found in 12/54 cases (22.2%) as compared to 25/54 metastatic lesions (46.3%;
      p = 0.01). The presence of neuroendocrine phenotype was not correlated with any
      clinical pathological parameter nor with a different proliferation index.
      However, patients having neuroendocrine cells in the primary tumor had a
      significantly shorter survival from the time of metastatic spread than those
      having not (33.3 vs. 55.5 months; p = 0.04). In summary, our data show that
      colorectal carcinoma metastases contain a higher percentage of neuroendocrine
      differentiated cells as compared to their corresponding primaries, a finding
      possibly related to the influence of chemotherapy in neuroendocrine
      differentiation during colorectal carcinoma progression.

PMID- 20812019
TI  - ERCP experience in patients with choledochoduodenostomy: diagnostic findings and
      therapeutic management.
AB  - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP), besides
      reducing the need for surgery in a wide spectrum of biliary disease, is
      increasingly be used for the treatment of biliary complications of surgery. In
      this paper, we review our experience with postoperative ERCPs required after
      biliary surgery with a special focus on side-to-side choledochoduodenostomy (CD).
      METHODS: The records of 70 patients with a history of CD who underwent ERCP from
      May 2000 to February 2006 were analyzed. RESULTS: There were 70 patients, 32
      (45.7%) women and 38 (35.6%) men, with a mean age of 56 (range, 21-80) years.
      Indications for ERCP were cholangitis in 46 (65.7%), abnormal liver function
      tests with abdominal pain and abnormal USG in 22 (31.4%), and abnormal liver
      function tests and abnormal USG in 2 (2.9%). Overall 133 ERCP were performed.
      Anastomotic stenosis was found in 14 (20%), benign biliary stricture above the
      anastomosis in 13 (18.6%), sump syndrome in 11 (15.7%), common bile duct stone in
      8 (11.4%), malignancy in 4 (5.7%), hepatolithiasis in 1 (1.4%), and secondary
      sclerosing cholangitis in 1 (1.4%). ERCP was normal in 18 (25.8%). Patients were
      managed by stone extraction in 8 (11%), stent insertion in 22 (36%), balloon
      dilatation in 15 (21%), nasobiliary drainage in 11 (16%), and bougie dilatation
      in 2 (3%) patients. CONCLUSIONS: We have reported one of the largest groups of
      patients with CD in the literature and showed that ERCP is a very important
      diagnostic and therapeutic tool for the management of biliary problems after CD.

PMID- 20812020
TI  - Low-volume bowel preparation is inferior to standard 4 1 polyethylene glycol.
AB  - BACKGROUND: Four liters or more of orally taken polyethylene glycol solution
      (PEG) has proved to be an effective large-bowel cleansing method prior to
      colonoscopy. The problem has been the large volume of fluid and its taste, which
      is unacceptable to some examinees. We aimed to investigate the effectiveness of 2
      l PEG combined with senna compared with 4 l PEG for bowel preparation. METHODS:
      The design was a single-center, prospective, randomized, investigator-blinded
      study with parallel assignment, in the setting of the Endoscopy Unit of Umea
      University Hospital. Outpatients (n = 490) scheduled for colonoscopy were
      enrolled. The standard-volume arm received 4 l PEG, and the low-volume arm
      received 36 mg senna glycosides in tablets and 2 l PEG. The cleansing result
      (primary endpoint) was assessed by the endoscopist using the Ottawa score. The
      patients rated the subjective grade of ease of taking the bowel preparation.
      Analysis was on an intention-to-treat basis. RESULTS: There were significantly
      more cases with poor or inadequate bowel cleansing after the low-volume
      alternative with senna and 2 l PEG (22/203) compared with after 4 l PEG (8/196, p
      = 0.027). The low-volume alternative was better tolerated by the examinees:
      119/231 rated the treatment as easy to take compared with 88/238 in the 4 l PEG
      arm (p = 0.001). CONCLUSIONS: 4 l PEG treatment is better than 36 mg senna and 2
      l PEG as routine colonic cleansing before colonoscopy because of fewer failures.

PMID- 20812021
TI  - Natural history of hepatitis B virus infection: pediatric perspective.
AB  - Hepatitis B virus (HBV) infection is an important disease globally. Chronic HBV
      infection may result in serious complications. Its transmission may be either
      perinatal or horizontal. Perinatal transmission is particularly important after
      the implementation of a universal vaccination program. Through either route,
      chronic carrier status is usually established in early childhood. The course of
      the disease course is determined by the host-virus interaction. The host's immune
      system initially tolerates the virus, and then gradually attempts to clear it.
      The virus, on the other hand, tries to avoid host immune system attack by a
      strategy involving targeted epitope mutations. By generating mutants, the virus
      can survive attacks from the host's immune system, enabling the infection to
      persist. Different individuals have different responses to HBV infection; genetic
      polymorphisms in cytokines, hormones, and other immune modulators may affect the
      final outcome of chronic HBV infection. Due to the implementation of a universal
      infant HBV vaccination program, HBV infection is now under control.
      Unfortunately, there still are some cases of vaccination failure. Very high
      maternal viremia, in utero infection, or escape mutants are possible reasons for
      vaccination failure. Immunocompromised hosts also risk vaccination failure. Blood
      or organ donors with occult HBV infection are possible sources for
      immunocompromised hosts. These victims of vaccination failure may exhibit a
      different disease course due to chronic HBV infection from those who acquired the
      infection before the universal vaccination era. The achievement of our ultimate
      goal of HBV elimination depends on a globally effective universal vaccination
      program, as well as the application of some novel successful medications to
      control those who are already infected.

PMID- 20812022
TI  - Hemodynamics model of fluid-solid interaction in internal carotid artery
      aneurysms.
AB  - The objective of this study is to present a relatively simple method to
      reconstruct cerebral aneurysms as 3D numerical grids. The method accurately
      duplicates the geometry to provide computer simulations of the blood flow.
      Initial images were obtained by using CT angiography and 3D digital subtraction
      angiography in DICOM format. The image was processed by using MIMICS software,
      and the 3D fluid model (blood flow) and 3D solid model (wall) were generated. The
      subsequent output was exported to the ANSYS workbench software to generate the
      volumetric mesh for further hemodynamic study. The fluid model was defined and
      simulated in CFX software while the solid model was calculated in ANSYS software.
      The force data calculated firstly in the CFX software were transferred to the
      ANSYS software, and after receiving the force data, total mesh displacement data
      were calculated in the ANSYS software. Then, the mesh displacement data were
      transferred back to the CFX software. The data exchange was processed in
      workbench software. The results of simulation could be visualized in CFX-post.
      Two examples of grid reconstruction and blood flow simulation for patients with
      internal carotid artery aneurysms were presented. The wall shear stress, wall
      total pressure, and von Mises stress could be visualized. This method seems to be
      relatively simple and suitable for direct use by neurosurgeons or
      neuroradiologists, and maybe a practical tool for planning treatment and follow
      up of patients after neurosurgical or endovascular interventions with 3D
      angiography.

PMID- 20812023
TI  - GPR39: a Zn(2+)-activated G protein-coupled receptor that regulates pancreatic,
      gastrointestinal and neuronal functions.
AB  - GPR39 is a vertebrate G protein-coupled receptor related to the
      ghrelin/neurotensin receptor subfamily. The receptor is expressed in a range of
      tissues including the pancreas, gut/gastrointestinal tract, liver, kidney and in
      some regions of the brain. GPR39 was initially thought to be the cognitive
      receptor for the peptide hormone, obestatin. However, subsequent in vitro studies
      have failed to demonstrate binding of this peptide to the receptor. Zn(2+) has
      been shown to be a potent stimulator of GPR39 activity via the Galpha(q),
      Galpha(12/13) and Galpha(s) pathways. The potency and specificity of Zn(2+) in
      activating GPR39 suggest it to be a physiologically important agonist. GPR39 is
      now emerging as an important transducer of autocrine and paracrine Zn(2+)
      signals, impacting upon cellular processes such as insulin secretion, gastric
      emptying, neurotransmission and epithelial repair. This review focuses on the
      molecular, structural and biological properties of GPR39 and its various
      physiological functions.

PMID- 20812025
TI  - Integration pattern of HIV-1 based lentiviral vector carrying recombinant
      coagulation factor VIII in Sk-Hep and 293T cells.
AB  - 293T and Sk-Hep-1 cells were transduced with a replication-defective self
      inactivating HIV-1 derived vector carrying FVIII cDNA. The genomic DNA was
      sequenced to reveal LTR/human genome junctions and integration sites. One hundred
      and thirty-two sequences matched human sequences, with an identity of at least
      98%. The integration sites in 293T-FVIIIDB and in Sk-Hep-FVIIIDB cells were
      preferentially located in gene regions. The integrations in both cell lines were
      distant from the CpG islands and from the transcription start sites. A comparison
      between the two cell lines showed that the lentiviral-transduced DNA had the same
      preferred regions in the two different cell lines.

PMID- 20812024
TI  - FBI-1 functions as a novel AR co-repressor in prostate cancer cells.
AB  - The pro-oncogene FBI-1, encoded by Zbtb7a, is a transcriptional repressor that
      belongs to the POK (POZ/BTB and Kruppel) protein family. In this study, we
      investigated a potential interaction between androgen receptor (AR) signaling and
      FBI-1 and demonstrated that overexpression of FBI-1 inhibited ligand-dependent AR
      activation. A protein-protein interaction was identified between FBI-1 and AR in
      a ligand-dependent manner. Furthermore, FBI-1, AR and SMRT formed a ternary
      complex and FBI-1 enhanced the recruitment of NCoR and SMRT to endogenous PSA
      upstream sequences. Our data also indicated that the FBI-1-mediated inhibition of
      AR transcriptional activity is partially dependent on HDAC. Interestingly, FBI-1
      plays distinct roles in regulating LNCaP (androgen-dependent) and PC-3 cell
      (androgen-independent) proliferation.

PMID- 20812026
TI  - Knowledge of breast cancer and screening practices among Iranian immigrant women
      in Toronto.
AB  - Breast cancer is a leading cause of mortality and morbidity in Canada. Secondary
      prevention through screening may enable early identification and treatment, but
      this is suboptimal among all Canadian women, particularly minority immigrant
      women. This cross-sectional exploratory study assessed breast health knowledge
      and practices among Iranian immigrant women residing in Toronto. Our sample
      included 50 adult women with no history of breast cancer. Results showed that,
      overall, participants had limited knowledge of breast cancer and screening
      practices. More than two-thirds had low knowledge scores; 22% did not know that
      the risk of breast cancer increases with age; about 50% did not know the
      recommended time interval for screening mammography; 72% did not know how
      frequently to undergo a clinical breast examination. Length of stay in Canada was
      associated with self-reported breast health practices. These findings highlight
      the need to educate Iranian immigrants about the role of screening to promote
      early identification of breast cancer in the absence of symptoms. Culturally
      sensitive educational materials should be developed to address their specific
      needs. Healthcare providers should also be educated about how to communicate
      breast health information effectively to immigrant women. Opportunistic teaching
      during each health encounter should be encouraged and reinforced.

PMID- 20812027
TI  - Religious coping and hospital admissions among adults with sickle cell disease.
AB  - Although a well-established literature implicates religiosity as a central
      element of the African American experience, little is known about how individuals
      from this group utilize religion to cope with specific health-related stressors.
      The present study examined the relation between religious coping and hospital
      admissions among a cohort of 95 adults with sickle cell disease-a genetic blood
      disorder that, in the United States, primarily affects people of African
      ancestry. Multiple regression analyses indicated that positive religious coping
      uniquely accounted for variance in hospital admissions after adjusting for other
      demographic and diagnostic variables. Specifically, greater endorsement of
      positive religious coping was associated with significantly fewer hospital
      admissions (beta = -.29, P < .05). These results indicate a need for further
      investigation of the roles that religion and spirituality play in adjustment to
      sickle cell disease and their influence on health care utilization patterns and
      health outcomes.

PMID- 20812028
TI  - A multicomponent approach to the synthesis of 1,3-dicarbonylic compounds.
AB  - A general synthesis of 1,3-dicarbonylic compounds using multicomponent reactions
      of isocyanides is described. The process involves a Passerini three-component
      condensation of glyoxal derivatives, isocyanides and acetic acid, followed by
      metal mediated reductive or solvolytic removal of the acid component. Noteworthy,
      reductive deacetoxylation of Passerini glyoxylamide adducts was successfully
      achieved using photochemically activated SmI(2). This procedure constitutes a
      novel convenient method for the direct synthesis of malonic retro-peptidic
      subunits.

PMID- 20812029
TI  - A novel four-component reaction for the synthesis of disubstituted 1,3,4
      oxadiazole derivatives.
AB  - The 1:1 imine intermediate generated by the addition of benzyl amine to
      cyclobutanone is trapped by (N-isocyanimino)triphenylphosphorane in the presence
      of an aromatic carboxylic acid leads to the formation of the corresponding
      iminophosphorane intermediate. Disubstituted 1,3,4-oxadiazole derivatives are
      formed via intramolecular aza-Wittig reaction of the iminophosphorane
      intermediate. The reactions were completed in neutral conditions at room
      temperature. The disubstituted 1,3,4-oxadiazole derivatives, were produced in
      excellent yields.

PMID- 20812030
TI  - Mdm2 inhibition induces apoptosis in p53 deficient human colon cancer cells by
      activating p73- and E2F1-mediated expression of PUMA and Siva-1.
AB  - Camptothecin (CPT) and Nutlin-3 caused apoptosis by increasing p53 protein and
      its activation in intestinal epithelial cells (IEC-6). We studied the
      effectiveness of these inducers on apoptosis in human colon cancer cells (Caco2)
      lacking p53 expression. CPT failed to activate caspase-3 and cause apoptosis in
      these cells. The absence of p53 expression, higher basal Bcl-xL and lower Bax
      proteins prevented CPT-induced apoptosis. However, the Mdm2 antagonist Nutlin-3
      induced apoptosis in a dose dependent manner by activating caspases-9 and -3.
      Nutlin-3 prevented the activation of AKT via PTEN-mediated inhibition of the PI3K
      pathway. Nutlin-3 increased the phosphorylation of retinoblastoma protein causing
      E2F1 release leading to induction of Siva-1. Nutlin-3-mediated degradation of
      Mdm2 caused the accumulation of p73, which induced the expression of p53 up
      regulated modulator of apoptosis (PUMA). E2F1 and p73 knockdown decreased the
      expression of Siva and PUMA, respectively and abolished Nutlin-3-induced caspase
      3 activation. Cycloheximide (CHX) inhibited Nutlin-3-induced Siva, Noxa, and PUMA
      expression and inhibited apoptosis in IEC-6 and Caco2 cells. These results
      indicate that translation of mRNAs induced by Nutlin-3 is critical for apoptosis.
      In summary, apoptosis in Caco2 cells lacking functional p53 occurred following
      the disruption of Mdm2 binding with p73 and Rb leading to the expression of pro
      apoptotic proteins, PUMA, Noxa, and Siva-1.

PMID- 20812031
TI  - Performance evaluation of PETbox: a low cost bench top preclinical PET scanner.
AB  - PURPOSE: PETbox is a low cost bench top preclinical PET scanner dedicated to
      pharmacokinetic and pharmacodynamic mouse studies. A prototype system was
      developed at our institute, and this manuscript characterizes the performance of
      the prototype system. PROCEDURES: The PETbox detector consists of a 20 * 44
      bismuth germanate crystal array with a thickness of 5 mm and cross-section size
      of 2.05 * 2.05 mm. Two such detectors are placed facing each other at a spacing
      of 5 cm, forming a dual-head geometry optimized for imaging mice. The detectors
      are kept stationary during the scan, making PETbox a limited angle tomography
      system. 3D images are reconstructed using a maximum likelihood and expectation
      maximization (ML-EM) method. The performance of the prototype system was
      characterized based on a modified set of the NEMA NU 4-2008 standards. RESULTS:
      In-plane image spatial resolution was measured to be an average of 1.53 mm full
      width at half maximum for coronal images and 2.65 mm for the anterior-posterior
      direction. The volumetric reconstructed resolution was below 8 mm(3) at most
      locations in the field of view (FOV). The sensitivity, scatter fraction, and
      noise equivalent count rate (NECR) were measured for different energy windows.
      With an energy window of 150 - 650 keV and a timing window of 20 ns optimized for
      mouse imaging, the peak absolute sensitivity was 3.99% at the center of FOV and a
      peak NECR of 20 kcps was achieved for a total activity of 3.2 MBq (86.8 MUCi).
      Phantom and in vivo imaging studies were performed and demonstrated the utility
      of the system at low activity levels. The quantitation capabilities of the system
      were also characterized showing that despite the limited angle tomography,
      reasonably good quantification accuracy was achieved over a large dynamic range
      of activity levels. CONCLUSIONS: The presented results demonstrate the potential
      of this new tomograph for small animal imaging.

PMID- 20812032
TI  - Synthesis and evaluation of 99mTc-labelled monoclonal antibody 1D09C3 for
      molecular imaging of major histocompatibility complex class II protein
      expression.
AB  - PURPOSE: It is known that major histocompatibility complex class II protein HLA
      DR is highly expressed in B-cell lymphomas and in a variety of autoimmune and
      inflammatory diseases. Therefore, a radiolabelled fully humanized IgG4 monoclonal
      antibody (mAb) can provide useful prognostic and diagnostic information. Aims of
      the present study were to radiolabel an anti-HLA-DR mAb with technetium-99m and
      to evaluate its binding specificity, tissue distribution and targeting potential.
      PROCEDURES: For labelling, we compared a direct method, after 2-mercaptoethanol
      (2-ME) reduction of disulphide bonds, with a two-step labelling method, using a
      heterobifunctional succinimidyl-6-hydrazinonicotinate hydrochloride chelator.
      Several in vitro quality controls and in vivo experiments in mice were performed.
      RESULTS: We obtained highest labelling efficiency (LE, >98%) and specific
      activity (SA; 5,550 MBq/mg) via the direct method. In vitro quality control
      showed good stability, structural integrity and retention of the binding
      properties of the labelled mAb. The biodistribution in mice showed high and
      persistent uptake in spleen and suggests kidney and liver-mediated clearance
      pathways. In tumour targeting experiments, we observed high uptake in HLA-DR
      positive xenografts compared to controls. In vivo binding was proportional to the
      number of injected cells. In the in vivo blocking assay, uptake of radiolabelled
      mAb was significantly decreased in mice pre-injected with 100-fold molar excess
      of unlabelled mAb. CONCLUSION: We efficiently labelled a humanized anti-HLA-DR
      mAb with (99m)Tc using a direct labelling method. Radiolabelled mAb binds to
      human HLA-DR antigens and therefore warrants further evaluation as a prognostic
      and diagnostic tool for patients with lymphoma or autoimmune diseases.

PMID- 20812033
TI  - Smoking and quality of life among female survivors of breast, colorectal and
      endometrial cancers in a prospective cohort study.
AB  - PURPOSE: To examine the association of smoking and quality of life (QOL) among
      survivors of breast, colorectal, or endometrial cancers. METHODS: The study
      included women who joined the Iowa Women's Health Study in 1986 and were
      subsequently diagnosed with breast, colorectal, or endometrial cancers through
      2004 (n = 1920). Smoking status was reported at baseline and in 2004; QOL was
      assessed in 2004 using the Medical Outcomes Study Short Form-36. Multivariate
      adjusted odds ratios were calculated to examine the associations of smoking
      status and poor QOL (score lower than one-half a standard deviation below the
      mean of the non-smokers). RESULTS: Compared with non-smokers, persistent smokers
      had higher likelihood of reporting poor Physical Functioning (odds ratio [OR] =
      2.40, 95% confidence interval [CI] = 1.32-4.37), Mental Health (OR = 1.92, CI =
      1.09-3.40), and Role Emotional (OR = 2.01, CI = 1.10-3.66), whereas former
      smokers had higher likelihood of reporting poor Physical Functioning (OR = 1.65,
      CI = 1.10-2.45), Mental Health (OR = 1.62, CI = 1.11-2.37), and General Health
      (OR = 1.51, CI = 1.03-2.21). A statistically significant trend toward higher
      likelihood of poor QOL was observed across smoking groups in Vitality, Physical
      Functioning, Mental Health, and Role Emotional. Further adjustment for physical
      activity resulted in attenuation of the odds ratios and p-values for trend.
      CONCLUSION: Among women with breast, colorectal, or endometrial cancers, smokers
      were more likely than former or non-smokers to have poor QOL. Physical activity
      explained, in part, the association between smoking status and QOL in our study.

PMID- 20812034
TI  - Interference microscopy in cell biophysics. 1. Principles and methodological
      aspects of coherent phase microscopy.
AB  - The purpose of our tandem publications is to review the applications of the
      coherent phase microscopy to cell biophysics. In this article, we briefly
      consider the fundamentals and methodological aspects of the coherent phase
      microscopy (CPM). One of important advantages of this method is a high
      sensitivity of CPM images to changes in physical-chemical properties of
      biological samples. The optical path length difference (OPLD), measured with CPM
      instruments in different domains of an object, serves as the informative optical
      parameter used for visualization of individual cells or intracellular organelles.
      Metabolically dependent variations of CPM images reflect changes in the
      functional state of biological objects. In the next article, we review results of
      CPM studies of different cells and intracellular energy-transducing organelles.

PMID- 20812035
TI  - Activation of Notch signal pathway is associated with a poorer prognosis in acute
      myeloid leukemia.
AB  - OBJECTIVE: Notch signal pathway plays a fundamental role in regulating
      haematopoietic development. It is also an important mediator of growth and
      survival in several cancer types, with Notch pathway genes functioning as
      oncogenes or tumor suppressors in different cancers. However, the clinical role
      of Notch signal pathway in acute myeloid leukemia (AML) remains unclear. METHODS:
      To address this problem, we investigated the gene expression levels of Notch
      signal pathway members (Notch1, Jagged1 and Delta1) in bone marrow mononuclear
      cells by real-time quantitative PCR in a cohort of 100 patients with newly
      diagnosed de novo AML and normal marrow donors. The prognostic values of the
      three molecules in AML were also analyzed. RESULTS: Comparing with the normal
      controls, we show the transcriptional up-regulation of Notch1, Jagged1 and Delta1
      in the bone marrow of AML patients with statistic differences (P = 0.008, 0.01
      and 0.01, respectively). In addition, univariate analysis of factors associated
      with relapse-free survival and overall survival showed a significantly shorter
      survival in the patients with unfavorable karyotype, higher Notch1 expression,
      higher Jagged1 expression, or higher Delta1 expression. Moreover, Cox
      proportional hazards multivariate analysis of the univariate predictors
      identified karyotype and gene expression levels of Notch1, Jagged1 and Delta1 as
      independent prognostic factors for relapse-free survival and overall survival.
      Furthermore, the prognostic significance of Notch1, Jagged1 and Delta1 expression
      was more obvious in the subgroup of patients with intermediate-risk cytogenetics.
      CONCLUSION: Taken together, our data suggest for the first time that the
      activation of Notch pathway may indicate a poor prognosis in AML. Especially,
      Notch1, Jagged1 and Delta1 expression may be relevant prognostic markers in
      intermediate risk AML.

PMID- 20812036
TI  - Education and levels of salivary cortisol over the day in US adults.
AB  - BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenal axis is
      hypothesized to be an important pathway linking socioeconomic position and
      chronic disease. PURPOSE: This paper tests the association between education and
      the diurnal rhythm of salivary cortisol. METHODS: Up to eight measures of
      cortisol (mean of 5.38 per respondent) over 2 days were obtained from 311
      respondents, aged 18-70, drawn from the 2001-2002 Chicago Community Adult Health
      Study. Multi-level models with linear splines were used to estimate waking level,
      rates of cortisol decline, and area-under-the-curve over the day, by categories
      of education. RESULTS: Lower education (0-11 years) was associated with lower
      waking levels of cortisol, but not the rate of decline of cortisol, resulting in
      a higher area-under-the-curve for more educated respondents throughout the day.
      CONCLUSIONS: This study found evidence of lower cortisol exposure among
      individuals with less education and thus does not support the hypothesis that
      less education is associated with chronic over-exposure to cortisol.

PMID- 20812037
TI  - Dynamics of changes in self-efficacy and locus of control expectancies in the
      behavioral and drug treatment of severe migraine.
AB  - BACKGROUND: Modification of expectancies (headache self-efficacy and headache
      locus of control) is thought to be central to the success of psychological
      treatments for migraine. PURPOSE: The purpose of this study is to examine
      expectancy changes with various combinations of Behavioral Migraine Management
      and migraine drug therapies. METHODS: Frequent migraine sufferers who failed to
      respond to 5 weeks of optimized acute migraine drug therapy were randomized to a
      2 (Behavioral Migraine Management+, Behavioral Migraine Management-) * 2 (beta
      blocker, placebo) treatment design. RESULTS: Mixed models for repeated measures
      analyses (N = 176) revealed large increases in headache self-efficacy and
      internal headache locus of control and large decreases in chance headache locus
      of control with Behavioral Migraine Management+ that were maintained over a 12
      month evaluation period. Chance headache locus of control and socioeconomic
      status moderated changes in headache self-efficacy with Behavioral Migraine
      Management+. CONCLUSIONS: The "deficiency" hypothesis best explained how patient
      characteristics influenced changes in of headache self-efficacy with Behavioral
      Migraine Management.

PMID- 20812038
TI  - [Research and application in the dialog].

PMID- 20812039
TI  - [Selection of scientific contributions to the DGU Congress 2010.].

PMID- 20812041
TI  - [Academy Spring forum: current & practice relevant topics in Urology in 2010].

PMID- 20812042
TI  - [Benign prostatic hyperplasia and urolithiasis].
AB  - Benign prostatic hyperplasia and urolithiasis are widespread diseases and are two
      of the most important elements of the urological therapeutic spectrum. This
      article gives an overview of the most interesting publications on the subject
      from the past few years. Particularly the link with cardiovascular risk factors
      like obesity and diabetes appears to be stronger than supposed. The diagnostic
      and therapeutic tools of the future will be developed with respect to this.

PMID- 20812043
TI  - [Diagnosis and treatment of overactive bladder, neurourology, urogynaecology and
      urinary stress incontinence: latest publications from 2009 and 2010].
AB  - The current review presents a summary of the most important manuscripts
      concerning the topics of overactive bladder, neurourology, genital prolapse and
      male and female urinary stress incontinence published in the year 2009 and the
      first 4 months of 2010 in peer-reviewed journals. The literature research was
      focussed on clinically relevant human studies with influence on diagnosis and
      therapeutic strategies of these diseases.Most of the published manuscripts
      focussed on the fields of overactive bladder and female urinary stress
      incontinence during the last 16 months. Some of the studies had very high
      evidence levels and confirmed new therapeutic strategies. Publications focussing
      on male urinary stress incontinence were of limited numbers in the year 2009 and
      did not change the clinical armamentarium significantly.

PMID- 20812044
TI  - [Andrology: varicocele: an update].
AB  - Varicocele is a common finding in approximately 20% of adolescents and adult men
      and in about 40% of infertile patients. Although numerous theories addressing the
      deteriorating impact on the testis are known, the direct connection between
      varicocele and infertility is not clear. It is well known that after operative
      therapies an improvement in sperm quality is found. However, the impact on
      pregnancy in an infertile coupleship is controversial. While the most recent meta
      analysis found an increased pregnancy rate after therapy, the Cochrane Reviews
      with the last update in 2009 did not. In summary, operative therapy seems
      justified in selected patients with infertility.

PMID- 20812045
TI  - [Germ cell cancer--an update].
AB  - Recently a rise in the incidence of testicular germ cell cancer (TGCC) has been
      repeatedly reported in Germany (18% during the period 2000-2006). Future
      investigations are needed to examine causes for this increase in TGCT. The
      mortality rates in the western and eastern parts of Germany converge, but there
      is still a significantly higher mortality rate in the eastern part. Again future
      investigations are needed to examine causes for this phenomenon. In cases of
      testicular microlithiasis, testicular biopsies should be considered if further
      factors representing testicular dysgenesis syndrome are present, such as
      infertility, atrophic testes, and undescended testes. One course of adjuvant BEP
      reduces the risk of relapse by approximately 90% and may be a new option as the
      initial treatment for all CS1 NSGCT. Patients obtaining a CR (<1 cm) after first
      line chemotherapy can be safely observed without PC-RPLND. Relapses are rare and
      potentially curable with further treatment.

PMID- 20812046
TI  - [Prostate cancer: an update].
AB  - 2009 Has been a year of high profile publishing about prostate cancer (PCa): To
      call in the first instance the S3 guideline and the ERSPC. The ERSPC especially
      as the basis for that in addition to the detection of prostate cancer, the
      treatment must be differentiated; overtreatment in particular may be avoided
      through the implementation of active surveillance protocols. In radical
      prostatectomy (RPx), increasingly the therapeutic value of lymphadenectomy is
      detected. Current issues in radiation oncology concern the efficacy and
      indications of brachytherapy, dose escalation with external beam radiotherapy and
      the differential indication of adjuvant vs. salvage radiotherapy after RPx.
      Similarly, the indication for salvage RPx after primary radiotherapy. To mention
      in systemic therapy are the GnRH antagonists, the so-called super-antiandrogens
      and the different approaches to immunotherapy of prostate cancer.

PMID- 20812047
TI  - [Diagnostic work-up and treatment of bladder cancer: current developments].
AB  - Forty percent of patients with superficial bladder carcinoma progress towards
      muscle-invasive carcinoma despite initial therapy. Emergent technologies in the
      diagnostics and therapy of superficial bladder carcinoma including fluorescence
      cystoscopy are able to reduce recurrence and progression rates. Nevertheless to
      date no trial was able to show a benefit with regard to cancer-specific and
      overall survival using these new technologies. Lymph vessel invasion has been
      introduced as a new prognostic marker in muscle-invasive bladder carcinoma that
      can be easily incorporated into routine clinical practice. Furthermore adjuvant
      chemotherapy has been identified along with lymph node density as a statistically
      significant marker for survival in muscle-invasive bladder carcinoma which should
      be investigated in prospective clinical trials. In metastatic bladder carcinoma,
      vinflunine was approved as second-line chemotherapy for patients who failed
      cisplatin-based chemotherapy. This article critically reviews the emergent
      developments of the last 12-15 months and comments on their clinical efficacy for
      the treatment of bladder carcinoma.

PMID- 20812048
TI  - [Renal cell carcinoma: recent developments in diagnostics and therapy].
AB  - This review highlights new strategies in the treatment of renal cell carcinoma
      (RCC). The benign or malignant status of renal masses in preoperative imaging as
      well as the detection of metastases and their differentiation from secondary
      malignancies is discussed. For the prognostic stratification of RCC the TNM
      system has been adopted. Nephron-sparing (NS) techniques of laparoscopy,
      radiofrequency and cryoablation are critically compared and the newest results of
      robotic-assisted (DaVinci) NS surgery are given. The special question of
      cytoreductive surgery in primary metastatic disease and the question of adjuvant
      immunotherapy are raised. New medical treatment strategies including new
      substances, vaccines and the possibility of sequential therapy are discussed.

PMID- 20812050
TI  - [Adipocytokines in rheumatoid arthritis and obesity].
AB  - In obese rheumatoid arthritis (RA) patients inflammatory mechanisms and
      cardiovascular secondary disorders are possibly related to changed expression of
      adipocytokines. Various adipocytokines and inflammatory parameters were examined
      in 112 patients (23.2% men; 76.8% women) suffering from RA: leptin, adiponectin,
      visfatin, sCD40 L, CRP, and ESR. Average BMI was 27.6 (+/-5.6). Leptin and BMI as
      well as visfatin and BMI correlated positively, BMI and adiponectin, however,
      showed a negative correlation. Significant differences between normal-weight and
      obese RA patients were found in both leptin and adiponectin measurements.
      Visfatin showed a positive correlation with CRP; sCD40 ligand which is a marker
      for increased T-cell activity correlated with CRP and ESR. Patients with low
      adiponectin levels (<10 microg/ml) more often suffered from cardiovascular
      diseases (28.6%) than those with enhanced adiponectin (14.3%). Increased pro
      inflammatory leptin and decreased anti-inflammatory adiponectin in obese RA
      patients can be associated with RA activity and enhanced cardiovascular risk.

PMID- 20812051
TI  - Expected frequency of femoral neck fractures by fall in the osteoporotic and
      osteopenic East Slovak female population: Epidemiological study.
AB  - OBJECTIVE OF THE STUDY: To compare an expected frequency of pathological FSI
      values with an expected frequency of pathological BMD (T-score < or = -2.5 SD) in
      the total hip area in the East Slovak female population. PATIENTS AND METHODS: We
      analyzed the data in the sample of 3,215 East Slovak women with a primary or
      secondary osteopenia and osteoporosis and with risk factors for osteoporosis,
      aged 20-89 years, x = 58.9 years, 95% CI (55.15; 60.35). Measured variables: T
      score total hip left and FSI left (femur strength index with dual energy X-ray
      absorptiometry. RESULTS: In the East Slovak female population we can expect 6.25%
      of women with osteoporosis in the total hip area and 14.54% of women with FSI <1,
      i.e. these women will suffer a femoral neck fracture in case of a fall. The
      expected frequency of the incidence of pathological FSI values of the East Slovak
      female population is 2.33 times higher than the expected frequency of the
      incidence of pathological T-score for osteoporosis measured in the total hip
      area. CONCLUSIONS: The measurement of FSI variable values may discover a higher
      percentage of women with a risk of femoral neck fracture by fall than the
      measurement of BMD variable values in the total hip area. This disproportion
      shows that even a patient with osteopenia measured in the total hip area may
      sustain a femoral neck fracture by fall, when she has adverse values of geometric
      variables of proximal femur (biomechanically unfavourable proximal femur
      configuration).

PMID- 20812049
TI  - [Adipokine update - new molecules, new functions].
AB  - The prevalence of obesity is rising worldwide. Recent research findings show that
      adipose tissue is a highly active endocrine organ, which is involved in many
      physiological processes. These metabolic processes are influenced by products of
      the adipose tissue, so-called adipokines, which play a crucial role in the
      pathogenesis of the metabolic syndrome and cardiovascular disease. In addition,
      the two major fat depots - intraabdominal and subcutaneous - differ in their
      ability to secrete adipokines. In recent years the importance of the association
      between intraabdominal fat and the development of insulin resistance, diabetes
      mellitus type 2 and dyslipidemia was recognized. Therefore, accumulation of
      visceral adipose tissue contributes due to its ability to secrete a different
      pattern of adipokines to increased morbidity and mortality. This review aims to
      characterize novel, newly recognized adipokines and to discuss their roles in the
      pathogenesis of insulin resistance and atherosclerosis, as well as other
      metabolic complications.

PMID- 20812052
TI  - Incidences of menstrual cycle abnormalities in adolescence, and matches between
      the age at menarche and the development of menstrual cycle abnormalities.
AB  - In this study the clinical data of all girls who visited the ambulance for
      paediatric and adolescent gynaecology at the university clinic for gynaecology
      and obstetrics in Vienna between 2001 and 2008 because of menstrual cycle
      abnormalities were used (n = 255). Most frequently, the girls suffered from
      dysmenorrhoea (29%), tempoanomaly (24%) and metrorrhagia (19%). For 57%, it was
      possible to find an underlying cause, mainly (24%) a hormonal one. The therapy
      was in 54% of all cases hormonal. In a second step, the study analyses matches
      between the age at menarche and the development of menstrual cycle abnormalities.
      Girls with primary amenorrhoea were excluded (n = 219). The study shows that
      every age of menarche has its special kind of menstrual cycle abnormality. Only
      if the menarche had set in at the age of 16, two kinds were named with equal
      frequency.

PMID- 20812053
TI  - [Microvascular and macrovascular complications in children and adolescents with
      type 1 diabetes mellitus].
AB  - Diabetes-related microvascular and macrovascular complications, as retinopathy,
      nephropathy and neuropathy are life-threatening complications in children and
      adolescents with type 1 diabetes mellitus (T1DM). Risk factors for the
      development of complications are longer duration of diabetes, older age and
      puberty. Further risk factors include smoking, hypertension, higher body mass
      index and dyslipoproteinaemia. Therefore prevention and screening for
      complications is an important part in the care of children and adolescents with
      T1DM. Target levels to reduce the risk of microvascular and macrovascular
      complications in children and adolescents with T1DM are the following:
      HbA1c<7.5%, lipids in normal range, blood pressure<90th percentile by age, sex
      and height, BMI<95th percentile, no smoking and physical activity. Screening for
      retinopathy and microalbuminuria should start from 11 years with two years
      diabetes duration and from 9 years with 5 years duration and after 2 years
      diabetes duration in an adolescent. Thereafter screening should be performed
      annually. Blood pressure should be measured at least annually. Screening for
      fasting blood lipids should be performed soon after diagnosis in all children
      with T1DM aged over 12 years. If normal results are obtained, this should be
      repeated every 5 years.

PMID- 20812054
TI  - [The Vienna School of Water Hygiene from the End of World War II until now].
AB  - After the economic stagnation of the 1930s and World War II the water-hygiene had
      to revive. Besides basic research for large projects as the 3rd Viennese water
      conduct, the Danube hydroelectric power station in Hainburg and the
      Marchfeldkanal new fields were opened. The evidence of fecal spring-water
      contamination by determination of the spectral-absorption-coefficients avoids the
      delay by bacterial cultivation and enables immediate satellite-transmission to
      central stations for turning-off the afflux. Determination of the origin (human
      and ruminant) of isolated E. coli by Real-time-PCR indicates necessities for
      sanitation. Investigation on UV-water-disinfection, considering also the
      formation of carcinogenic and genotoxic compounds, resulted in the only European
      national UV-norm and the establishment of one of the wordwide four testing
      institutions of UV-water-disinfection. The department for water-hygiene of the
      Medical University of Vienna carries out specific duties in various national
      committees of public health importance as well as in collaboration with EU, WHO,
      ISO and other international commissions.

PMID- 20812055
TI  - Digital clubbing in primary intestinal lymphangiectasia: a case report.
AB  - Primary intestinal lymphangiectasia (PIL), also known as Waldmann's disease, is a
      rare disorder characterized by dilated intestinal lacteals resulting in lymph
      leakage into the small bowel lumen and responsible for protein-losing enteropathy
      leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. The symptoms
      usually start in early infancy. We report a case of secondary
      hyperparathyroidism, osteopenia, monoclonal gammopathy and digital clubbing in a
      57-year-old patient with a 12-year history of discontinuous diarrhea.
      Malabsorption with inability to gain weight, and finally weight loss and
      formation of leg edema were associated with protein-losing enteropathy. A low-fat
      diet associated with medium-chain triglyceride supplementation was clinically
      effective as medical management in reducing diarrhea and leg edema, and promoting
      weight gain. Double-balloon enteroscopy and small bowel biopsy histopathology
      confirmed dilated intestinal lacteals. Digital clubbing associated with primary
      intestinal lymphangiectasia which may causally be related to chronic platelet
      excess has not been reported before.

PMID- 20812057
TI  - Editorial. Cognitive Neuropsychology.

PMID- 20812118
TI  - Assessing the use of 3H-3He dating to determine the subsurface transit time of
      cave drip waters.
AB  - (3)H-(3)He measurements constitute a well-established method for the
      determination of the residence time of young groundwater. However, this method
      has rarely been applied to karstified aquifers and in particular to drip water in
      caves, despite the importance of the information which may be obtained. Besides
      the determination of transfer times of climate signals from the atmosphere
      through the epikarst to speleothems as climate archives, (3)H-(3)He together with
      Ne, Ar, Kr, Xe data may also help to give new insights into the local
      hydrogeology, e.g. the possible existence of a perched aquifer above a cave. In
      order to check the applicability of (3)H-(3)He dating to cave drips, we collected
      drip water samples from three adjacent caves in northwestern Germany during
      several campaigns. The noble gas data were evaluated by inverse modelling to
      obtain recharge temperature and excess air, supporting the calculation of the
      tritiogenic (3)He and hence the (3)H-(3)He age. Although atmospheric noble gases
      were often found to be close to equilibrium with the cave atmosphere, several
      drip water samples yielded an elevated (3)He/(4)He ratio, providing evidence for
      the accumulation of (3)He from the decay of (3)H. No significant contribution of
      radiogenic (4)He was found, corresponding to the low residence times mostly in
      the range of one to three years. Despite complications during sampling,
      conditions of a perched aquifer could be confirmed by replicate samples at one
      drip site. Here, the excess air indicator DeltaNe was about 10 %, comparable to
      typical values found in aquifers in mid-latitudes. The mean (3)H-(3)He age of 2.1
      years at this site presumably refers to the residence time in the perched aquifer
      and is lower than the entire transit time of 3.4 years estimated from the tritium
      data.

PMID- 20812119
TI  - Linking chloride mass balance infiltration rates with chlorofluorocarbon and SF6
      groundwater dating in semi-arid settings: potential and limitations.
AB  - In the framework of the investigation of enrichment processes of nitrate in
      groundwater of the Kalahari of Botswana near Serowe, recharge processes were
      investigated. The thick unsaturated zone extending to up to 100 m of mostly
      unconsolidated sediments and very low recharge rates pose a serious challenge to
      study solute transport related to infiltration and recharge processes, as this
      extends past the conventional depths of soil scientific investigations and is
      difficult to describe using evidence from the groundwater due to the limitations
      imposed by available tracers. To determine the link between nitrate in the vadose
      zone and in the uppermost groundwater, sediment from the vadose zone was sampled
      up to a depth of 15-20 m (in one case also to 65 m) on several sites with natural
      vegetation in the research area. Among other parameters, sediment and water were
      analysed to determine chloride and nitrate concentration depth profiles. Using
      the chloride mass balance method, an estimation of groundwater infiltration rates
      produced values of 0.2-4 mm a(-1). The uncertainty of these values is, however,
      high. Because of the extreme thickness of the vadose zone, the travel time in the
      unsaturated zone might reach extreme values of up to 500 years and more. For
      investigations using groundwater, we applied the chlorofluorocarbons CFC-113, CFC
      12, sulphur hexafluoride (SF(6)) and tritium to identify potential recharge, and
      found indications for some advective transport of the CFCs and SF(6), which we
      accounted for as constituting potential active localised recharge. In our
      contribution, we show the potential and limitations of the applied methods to
      determine groundwater recharge and coupled solute transport in semi-arid
      settings, and compare travel time ranges derived from soil science and
      groundwater investigations.

PMID- 20812120
TI  - The national health literacy action plan: the time has come for action.

PMID- 20812121
TI  - Testing implicit assumptions and explicit recommendations: the effects of
      probability information on risk perception.
AB  - When people underestimate a risk, often probability information is communicated
      because of the implicit assumption that it will raise people's risk estimates as
      a result of these objective facts. Also, scientific literature suggested that
      stressing the cumulative aspects of a risk might lead to higher susceptibility
      perceptions than only emphasizing the single incident probability. Empirical
      evidence that supports the effectiveness of these strategies, however, is
      lacking. In two studies, we examined whether cumulative and single incident
      probability information on sexually transmitted infections leads to higher
      perceived susceptibility for Chlamydia and HIV. Contrary to assumptions and
      recommendations, results showed that both types of probability information may
      result in people feeling less susceptible toward Chlamydia and having less
      intention to reduce the risk. For HIV, no effects were found. These results
      contradict implicit assumptions and explicit recommendations concerning the
      effects of probability information on risk perceptions.

PMID- 20812122
TI  - Quantifying word use to study health literacy in doctor-patient communication.
AB  - Most health literacy research to date has assessed health literacy using either
      general reading tests or text-based appraisals of reading and numeracy skills,
      yet the definition of health literacy includes domains beyond reading ability.
      Effective oral communication between doctor and patient is an important component
      of health literacy, but only recently have efforts been made to develop measures
      that tap into domains beyond those that can be assessed with text-based measures.
      Focusing on oral exchange, this article describes computer-assisted approaches to
      quantifying word use and the development of three word-use measures that can be
      used to study health literacy in transcripts of clinical encounters. The measures
      can be used to assess either the expressed literacy level of patients or the
      aural literacy demands made by doctors. Importantly, the computer-assisted
      quantitative measures described here make it possible for word use to be analyzed
      at a level of detail that human raters would be hard pressed to attain.

PMID- 20812123
TI  - The use of gain- or loss-frame messages and efficacy appeals to dissuade
      excessive alcohol consumption among college students: a test of psychological
      reactance theory.
AB  - The present study applies psychological reactance theory (PRT) to examine the
      effectiveness of a 2 (frame: gain, loss) x 2 (efficacy: present, not present)
      experiment to determine best practices in dissuading excessive alcohol
      consumption among college students. Results from the structural model revealed no
      association between a perceived threat to choose and message frame or efficacy
      appeals. As anticipated, a perceived threat to freedom was positively associated
      with state reactance, which in turn was positively associated with a boomerang
      effect and negatively associated with favorable source appraisal. State reactance
      was not associated with favorable attitudes toward preventing the overconsumption
      of alcohol. In addition to main effects, interactions between message frame and
      efficacy appeal with four person factors (participant age, trait reactance,
      perceived health risk, and alcohol consumption) were examined. Individuals
      perceiving health risk to be low would benefit from gain-frame messages, whereas
      loss-frame messages would be most effective for heavy drinkers. Finally, when
      communicating to underage drinkers, our results support using efficacy appeals
      when accompanied by a loss-frame message.

PMID- 20812124
TI  - Who are the opinion leaders? The physicians, pharmacists, patients, and direct-to
      consumer prescription drug advertising.
AB  - A popular perception holds that physicians prescribe requested drugs to patients
      influenced by mass mediated direct-to-consumer prescription drug advertising. The
      phenomenon poses a serious challenge to the two-step flow model, which emphasizes
      the influence of opinion leaders on their followers and their legitimating power
      over the informing power of the mass media. This study investigates a 2002 Food
      and Drug Administration (FDA) survey and finds that patients searching for drug
      information through mass and hybrid media in newspapers and magazines' small
      print, the Internet, and toll-free numbers are more likely to seek information
      through interpersonal communication channels like health care providers. Patients
      using small print, toll-free numbers, one's own physician, and other physicians
      are associated with influencing their physicians with various drug-requesting
      behaviors. But physicians only prescribe requested drugs to patients who are
      influenced by other health care providers, such as pharmacists and other
      physicians, not the mass media. The influence of expert opinion leaders of drugs
      is so strong that the patients even would switch from their own unyielding
      physicians who do not prescribe drugs as advised by the pharmacists. Physicians
      and patients all are influenced more by other expert opinion leaders of drugs
      than by the mass media and therefore still uphold the basic tenet of the two-step
      model.

PMID- 20812125
TI  - Perceptions of smoking prevalence by youth in countries with and without a
      tobacco advertising ban.
AB  - This study examined a proposed mechanism by which exposure to cigarette
      advertising may mediate the subsequent smoking of youth. We hypothesized that
      children's exposure to cigarette advertising leads them to overestimate the
      prevalence of smoking, and that these distorted perceptions, in turn, lead to
      increased intentions to smoke. Children in Finland, where there has been a total
      tobacco advertising ban since 1978, were compared with children in the United
      States at a time when tobacco advertising was ubiquitous. Samples of 477 8- to 14
      year-old Helsinki students and 453 8- to 14-year-old Los Angeles students whose
      lifetime cigarette use consisted of no more than a puff of a cigarette were
      administered questionnaires in their classrooms. The primary hypothesis was
      confirmed. Los Angeles youth were significantly more likely than Helsinki youth
      to overestimate the prevalence of adult smoking, in spite of the fact that actual
      adult smoking prevalence in Helsinki was almost twice that of Los Angeles adults.
      A similar, significant pattern for perceived peer smoking was obtained, with Los
      Angeles youth being more likely than Helsinki youth to overestimate prevalence,
      in spite of the actual greater prevalence of youth smoking in Helsinki.

PMID- 20812126
TI  - Services and information for sexually compulsive students on college counseling
      center websites: results from a national sample.
AB  - One factor that may prevent a small but significant percentage of college
      students from achieving sexual health is sexual compulsivity, a problem of sexual
      control that is associated with a number of negative health outcomes, including
      high HIV risk behavior. In this study we content analyzed a randomly selected
      stratified national sample of 203 4-year U.S. colleges' counseling center
      websites to assess the degree to which such sites feature information and
      reference services for sexually compulsive students. Results revealed that sexual
      compulsivity communications were rare, especially in comparison with
      communications for other mental health issues. For instance, less than 5% of
      counseling centers spoke of individual counseling opportunities for students
      struggling with sexual compulsivity, while between 60% and 80% of counseling
      centers advertised their capacity to provide individual counseling for students
      struggling with alcohol and substance abuse, depression, stress/anxiety, and
      pathological eating. Possible explanations for the paucity of sexual compulsivity
      messages are discussed.

PMID- 20812127
TI  - Perceived risks and protective strategies employed by young men who have sex with
      men (YMSM) when seeking online sexual partners.
AB  - This study examined the perceptions of risk by young men who have sex with men
      (YMSM) regarding meeting sexual partners through the Internet. Fifty-four YMSM
      ages 18-29 who reported engaging in bareback sex ("intentional unprotected anal
      intercourse in high-risk contexts") completed a structured assessment and a face
      to-face interview. Participants reported using the Internet to meet sexual
      partners at least once per week, having had multiple sexual partners in the past
      2 months (M = 10.50, SD = 9.25), and engaging in occasions of unprotected
      receptive (M = 5.35, SD = 6.76) and insertive (M = 5.06, SD = 10.11) anal
      intercourse. A third of the sample reported having had unprotected sex with a
      partner who was serodiscordant or of unknown serostatus. Despite the obvious HIV
      risks, the most commonly perceived risks included threats to physical safety and
      difficulties trusting a stranger. Risk reduction strategies included leaving
      information about partner and whereabouts with a friend, meeting in a public
      place, and screening partner through online chatting. Those YMSM who meet
      partners online may be at risk for physical violence in addition to HIV or
      sexually transmitted infections (STIs). Public health campaigns should increase
      awareness of safety concerns when meeting sexual partners online and support
      YMSM's self-protective actions.

PMID- 20812128
TI  - Analysis of the lateral push-off in the freestyle flip turn.
AB  - The aim of this study was to examine the contact phase during the lateral push
      off in the turn of front crawl swimming to determine which biomechanical
      variables (maximum normalized peak force, contact time, impulse, angle of knee
      flexion, and total turn time within 15 m) contribute to the performance of this
      turn technique. Thirty-four swimmers of state, national, and international
      competitive standard participated in the study. For data collection, the
      following equipment was used: an underwater force platform, a 30-Hz VHS video
      camera, and a MiniDv digital camera within an underwater box. Data are expressed
      as descriptive statistics. Inferential analyses were performed using Pearson's
      correlation and multiple linear regressions. All variables studied had a
      significant relationship with turn performance. We conclude that a turn executed
      with a knee flexion angle of between 100 degrees  and 120 degrees  provides
      optimum peak forces to generate impulses that allow the swimmer to lose less time
      in the turn without the need for an excessive force application and with less
      energy lost.

PMID- 20812129
TI  - Characterisation and immuno-stimulating activity of polysaccharides from Thai
      medicinal plants.
AB  - Water-soluble polysaccharides were isolated from the tubers of Butea superba
      Roxb. and Pueraria candollei Wall. Ex Benth. var. mirifica (Shaw et Suvat.) C.
      Niyomdham, the leaves of Centella asiatica (L.) Urb, Ocimum basilicum L., Psidium
      guajava and Andrographis paniculata (Burn. f.) Nees, the stems of Cymbopogon
      citratus (Stapf ExG), and the fruits of Psidium guajava and Scaphium scaphigerum.
      The immunological impacts of the polysaccharides on T-lymphocyte proliferation in
      vitro was investigated by flow cytometric (immunofluorescence) analysis using
      staphylococcal enterotoxin B (SEB) as a positive control. It was found that the
      polysaccharides enhanced T-lymphocyte proliferation, ranging from 4.5 to 27.0% at
      a concentration of 100 microg mL(-1), while the activity of SEB was 13.3%. The
      medicinal plants showing the highest immuno-stimulating activity were the tubers
      of Butea superba Roxb. The water-extracted tubers contained 60.0% (w/w)
      carbohydrates with 6.6% (w/w) uronic acid. The major constituent monosaccharides
      of the tubers were 28.2 mol% galactose, 10.5 mol% arabinose and 36.4 mol%
      glucose.

PMID- 20812130
TI  - Herbicidal effects of extracts and residue incorporation of Datura metel against
      parthenium weed.
AB  - The present study was designed to evaluate the herbicidal activity of Datura
      metel against the noxious weed parthenium (Parthenium hysterophorus L.). In a
      laboratory bioassay, the effect of aqueous, methanol and n-hexane shoot and root
      extracts of 5, 10, 15 and 20% w/v (on a fresh weight basis) concentration of D.
      metel were tested against the germination and seedling growth of parthenium. Both
      aqueous and methanol extracts markedly suppressed the germination and seedling
      growth of parthenium. Generally, the effect of shoot extracts was more pronounced
      than the effect of root extracts. In foliar spray bioassay, aqueous and methanol
      shoot extracts of 10% w/v (on dry weight bases) concentrations were sprayed on
      one-week and two-week-old pot-grown parthenium seedlings. Two subsequent sprays
      were carried out at five day intervals each. Both the aqueous as well as the
      methanol extracts significantly suppressed shoot length as well as shoot and root
      biomass of one-week and two-week-old parthenium plants. In residue incorporation
      bioassay, crushed shoots of D. metel were incorporated in the soil at 1, 2, ...
      5% w/w. Parthenium seeds were sown one week after residue incorporation and
      plants were harvested 40 days after sowing. Incorporation of 2-5% residues
      significantly reduced germination by 47-89%. Residues of 4 and 5% concentration
      significantly suppressed plant biomass by 90 and 97%, respectively. The present
      study concludes that root and shoots of D. metel contain herbicidal constituents
      for the management of parthenium weed.

PMID- 20812131
TI  - Molecular characterisation of UV and chemically induced mutants of Trichoderma
      reesei FCBP-364.
AB  - Cellulases are a highly diverse group of enzymes whose function is crucial to the
      healthy functioning of the biosphere, since more than half of all biomass on the
      planet consists of their substrate, cellulose. Trials were conducted to study the
      effect of mutagenesis by ultraviolet (UV) irradiation (5-40 min) and ethyl
      methane sulphonate (EMS) treatment (50-300 microg mL(-1)) to obtain hyperactive
      cellulase enzyme producers. Putative mutants of Trichoderma reesei FCBP-364 were
      selected on the basis of their bigger hydrolysing zone formation and compared to
      the parental strains quantitatively. UV- and EMS-treated putative mutants of the
      test strains exhibited a 1.5-2-fold enhancement in enzymatic activity over the
      parental strain. The profile of genetic variability among native and mutant
      derivatives was scrutinised through random amplification of polymorphic DNA
      polymerase chain reaction (RAPD-PCR). The scanned amplicons confirmed the
      modification in genetic make up which might be the cause of the stir up in the
      enzyme activity.

PMID- 20812132
TI  - Alpha-amylase production by toxigenic fungi.
AB  - This study is concerned with the screening of Alternaria alternata (Fr.) Keissler
      and Alternaria tenuissima (Kunze ex Pers.) Wilts strains for the biosynthesis of
      alpha-amylases. Nine strains of A. alternata and three strains of A. tenuissima
      were grown on enzyme production medium (EPM) and potato dextrose agar (PDA) using
      three pH levels (4.5-6.5); then the selected strains, able to produce bigger
      zones of starch hydrolysis on solid media, were subjected the testing of their
      amylolytic efficacy in liquid medium. In primary screening, the amylolytic
      activity of all the strains was tolerant to a wide range of initial culture pH
      values (4.5-6.5). Of all the cultures tested, A. alternata strains FCBP-100 and
      FCBP-385, and A. tenuissima strains FCBP-183 and FCBP-252 exhibited the maximum
      potential in terms of starch hydrolysis at pH 4.5 on EPM, and hence were selected
      for further studies. In secondary screening, the optimum pH of fermentation
      medium was adjusted to 4.5 using 0.05 M citrate buffer for the estimation of
      amylolytic enzyme activities. At 48 h incubation, the maximum alpha-amylase
      activity (31.8 units mL(-1)) was discerned by A. tenuissima strain FCBP-252.

PMID- 20812133
TI  - Herbicidal activity of Withania somnifera against Phalaris minor.
AB  - Herbicidal activity of Withania somnifera (L.) Dunal. was studied against
      Phalaris minor Retz., one of the most problematic weeds of wheat in Pakistan. In
      laboratory bioassays the aqueous, methanol and n-hexane extracts of 5, 10 and 15%
      w/v (fresh weight basis) of the roots and shoots of W. somnifera were applied.
      Extracts in the different solvents exhibited markedly variable herbicidal
      activities against germination and seedling growth of the target weed species.
      The methanol extracts showed the highest toxicity. Different concentrations of
      methanol shoot and root extracts declined the germination of P. minor by 21-71%,
      its shoot length by 40-72%, its root length by 50-99% and the plant biomass by 32
      83%. The aqueous extracts proved to be comparatively less toxic than the methanol
      extracts, where generally the highest concentration of 15% exhibited pronounced
      toxicity against the target weed species. There was up to 48, 51, 99 and 55%
      suppression of the weed's germination, shoot length, root length and plant
      biomass, respectively, due to the 15% aqueous root and shoot extracts. Generally,
      the n-hexane extracts of both roots and shoots exhibited insignificant or
      stimulatory effects against weed shoot length and plant biomass. In a foliar
      spray bioassay, aqueous and methanol shoot extracts of 10% w/v (dry weight basis)
      concentration were sprayed on one- and two-week old pot grown P. minor seedlings.
      Two subsequent sprays were carried out at five day intervals each. The aqueous
      extract significantly reduced the shoot and root dry biomass of one-week old P.
      minor plants. In a residue incorporation bioassay, crushed shoots of W. somnifera
      were incorporated in the soil at 1, 2, ... 5% w/w. Phalaris minor seeds were sown
      one week after residue incorporation and plants were harvested 45 days after
      sowing. The lower concentrations of 2 and 3% significantly reduced, while higher
      concentrations of 4 and 5% of residue incorporation completely arrested, the
      germination of P. minor. The present study concludes that both roots and shoots
      of W. somnifera contain herbicidal constituents against P. minor.

PMID- 20812134
TI  - Involvement of inducible nitric oxide synthase and cyclooxygenase-2 in the anti
      inflammatory effects of a red orange extract in human chondrocytes.
AB  - In the present study, a complex of compounds (red orange complex, ROC), obtained
      from three red orange varieties (Citrus sinensis varieties: Moro, Tarocco and
      Sanguinello), containing cyanidin glycosides, hydroxycinnamic acids, flavanone
      glycosides and ascorbic acid, was screened to discover new lead compounds in the
      suppression of the production of key molecules released during inflammatory
      events in interleukin-1beta (IL-beta) stimulated human primary chondrocytes. The
      expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX)-2
      and intercellular adhesion molecule-1 (ICAM-1), and the release of nitric oxide,
      prostaglandin (PG)E(2) and interleukin-8 (IL-8) were determined. Indomethacin was
      used as an anti-inflammatory drug reference. ROC acts as a potent inhibitor of
      iNOS and COX-2 gene expression while also suppressing the production of PGE(2)
      and nitrite in human chondrocytes. In addition, ROC induces a significant
      decrease in ICAM expression and IL-8 release. These findings suggest that ROC
      exerts anti-inflammatory effects probably through the suppression of COX-2 and
      iNOS expression.

PMID- 20812135
TI  - New antifungal steroids from Turbinaria conoides (J. Agardh) Kutzing.
AB  - Two new steroids 3,6,17-trihydroxy-stigmasta-4,7,24(28)-triene (1) and
      14,15,18,20-diepoxyturbinarin (3), together with a known compound, fucosterol
      (2), were isolated from the cyclohexane extract of Turbinaria conoides. The
      structures were elucidated on the basis of spectroscopic evidence. The isolated
      compounds were screened against a panel of microorganisms. Minimum inhibitory
      concentrations (MICs) were determined by the standard broth dilution method.
      Compounds 1-3 exhibited moderate antibacterial activity against the tested
      bacteria and inhibited the fungal growth with MIC values ranging from 2 to 16
      microg mL(-1). Compound 3 was found to be most potent against Aspergillus niger,
      with an MIC value of 2.0 microg mL(-1). The isolation of antifungal compounds
      from T. conoides is reported for the first time. These results suggested that
      14,15,18,20-diepoxyturbinarin (3) could be developed as a new lead antifungal
      agent.

PMID- 20812136
TI  - Stilbene production in cell cultures of Vitis vinifera L. cvs Red Globe and
      Michele Palieri elicited by methyl jasmonate.
AB  - Cell cultures obtained from Vitis vinifera cvs Michele Palieri and Red Globe were
      cultured in order to stimulate stilbene production. In the calli, stilbene
      production peaked at day 22 of culture for both cultivars; the main compound was
      trans-piceid, followed by cis-piceid. Methyl jasmonate, which was added to cell
      suspensions in the first half of the exponential growth phase, enhanced stilbene
      accumulation, producing mainly trans-piceid and epsilon-viniferin. Other
      stilbenoids, though in lower quantities, were identified by liquid
      chromatography/positive electrospray mass spectrometry. epsilon-Viniferin and
      trans-resveratrol were the main compounds released into the culture medium. The
      total quantity of stilbenes was genotype dependent, with a better response found
      for the cv Red Globe.

PMID- 20812138
TI  - Mirrored-self misidentification in a patient without dementia: evidence for right
      hemispheric and bifrontal damage.
AB  - Mirrored-self misidentification, often referred as the 'mirror sign', is a
      delusion characterized by the inability to recognize one's own reflected image,
      often associated with the intact capacity to recognize others in the mirror. It
      has been described mainly in moderate or severe dementia, especially Alzheimer's
      disease. In the few reported cases without global cognitive impairment, right
      hemispheric and frontal dysfunctions have been described. We report a 90-year-old
      man with abrupt onset of the mirror sign after a minor right hemispheric ischemic
      stroke. Neuropsychological testing revealed preserved cognitive capacities,
      except for mild to moderate impairment of visuospatial skills, suggesting right
      hemisphere dysfunction. Neuroimaging showed a small right dorsolateral frontal
      infarct, and bifrontal encephalomalacia, consistent with a past history of head
      trauma. Scattered ischemic white matter lesions in posterior periventricular
      regions were also seen. It seems that the mirror sign is a multifactorial
      phenomenon that usually requires right hemispheric dysfunction (perceptual
      abnormalities, loss of familiarity) and frontal damage (loss of judgement and
      inability to correct wrong beliefs). The right frontal dorsolateral prefrontal
      cortex seems to have a crucial role in self-recognition.

PMID- 20812137
TI  - The importance of multiple assessments of object knowledge in semantic dementia:
      the case of the familiar objects task.
AB  - Semantic dementia (SD) is characterized by a dramatic loss of conceptual
      knowledge about the meaning of words and the identity of objects. Previous
      research has suggested that SD patients' knowledge is differentially influenced
      by the disease and may decline at different degrees depending on a patient's
      everyday familiarity with certain items. However, no study has examined (a)
      semantic knowledge deterioration and (b) the potential significance of
      autobiographical experience for the maintenance of object concepts in the same
      cohort of SD patients by using comprehensive assessments of different aspects of
      object knowledge across an experience-based, distributed semantic memory network.
      Here, we tested four SD patients and three Alzheimer's disease (AD) control
      patients using a range of tasks - including naming, gesture generation, and
      autobiographical knowledge - with personally familiar objects or perceptually
      similar or different object analogs. Our results showed dissociations between
      performance on naming relative to other assessments of object knowledge between
      SD and AD patients, though we did not observe a reliable familiar objects
      advantage. We discuss different factors that may account for these findings, as
      well as their implications for research on SD.

PMID- 20812139
TI  - Neuropsychological evidence for a competitive bias against contracting stimuli.
AB  - Two experiments examined extinction to stimuli presented either with contracting
      or expanding motion. Experiment 1 used solid shapes which either increased or
      decreased in size rapidly, consistent with looming motion. Experiment 2 employed
      random dots so that stimulus size was not confounded with type of motion. In both
      experiments extinction was modulated by the type of motion presented, with
      extinction most evident when a contracting object was in the weaker visual field.
      In addition, in Experiment 2 there was evidence for grouping modulating
      extinction, when there were looming stimuli in both fields. The results suggest
      that looming motion is a powerful determinant of stimulus salience in selective
      attention.

PMID- 20812140
TI  - Two different mechanisms for omission and substitution errors in neglect
      dyslexia.
AB  - Neglect dyslexia is a reading disorder often associated with right-sided brain
      lesions. In reading single words, errors are mostly substitutions or omissions of
      letters that occupy the left-sided positions. Typically, these errors have been
      thought to depend on a single mechanism. Conversely, we propose that they are due
      to different mechanisms. In particular, a visuo-spatial mechanism is responsible
      for omissions and a perceptual integration process for substitution errors. We
      measured the performance of six patients with both neglect and neglect dyslexia,
      analyzing their reading errors as a function of letter spacing. According to our
      conjecture, letter spacing should increase omissions by moving part of the string
      further in the unattended space, while it should reduce substitutions by
      restoring the integration processes. Furthermore, we predict that letter spacing
      should be more effective with pseudowords compared to words, in that in this
      latter case lexical effects are supposed to influence attentional and perceptual
      processes. Accordingly, we found that for pseudowords only the two types of
      errors are differently affected by this manipulation and only omissions correlate
      with the severity of the disorder in visuo-spatial tasks.

PMID- 20812142
TI  - Developmental profile and trajectory of neuropsychological skills in a child with
      Kabuki syndrome: implications for assessment of syndromes associated with
      intellectual disability.
AB  - Kabuki syndrome (KS) is a rare genetic syndrome involving dysmorphic facial
      features,and reports of intellectual disability (ID). We examined the
      developmental trajectory of neuropsychological skills in a child with KS (seen at
      ages 4, 6, 7, 9, and 11). Examination of raw and age-corrected standard scores
      suggests that language-based skills developed appropriately, but visually based
      skills slowed and reached a plateau. Executive dysfunction and mood symptoms were
      also observed. While ID is described as a core feature of KS,some patients may
      not meet diagnostic criteria for ID, and may be better described as having
      specific deficits in nonverbal skills. Longitudinal neuropsychological assessment
      of children with KS and other syndromes associated with ID is warranted to
      understand the true prevalence of ID versus isolated cognitive impairments.

PMID- 20812143
TI  - Network biology as a new approach to drug discovery.
AB  - The decline in productivity of the pharmaceutical industry may stem, at least in
      part, from underestimating the complexity of human disease. While a disease
      relevant gene or protein may initially seem to be an attractive drug target,
      appreciating its role in the network of pathways involved in a disease provides a
      better perspective for making this decision. In some cases, off-target effects or
      redundancy in the network can negate the potential efficacy of a new drug. Even a
      successful drug, such as imatinib (Gleevec), may be less selective than
      originally thought, resulting in important, and sometimes useful, consequences.
      Advances in the area of network biology provide an important perspective on the
      potential of a drug target, and are being applied to various diseases. The impact
      of these advances on the field of drug discovery is assessed.

PMID- 20812144
TI  - Conformational ensembles, signal transduction and residue hot spots: application
      to drug discovery.
AB  - A key step in drug development is the identification of both a protein target and
      its topological cellular network location and interactions, with regard to
      information flow in disease-causing events and to medication effects. Information
      flow involves a cascade of binding or covalent modification processes, with each
      step being affected by those that occur previously. Proteins are flexible, and
      information flows via dynamic changes in the distribution of conformational
      protein ensembles; molecular recognition is mainly determined by these changes.
      Drug discovery often focuses on signaling proteins situated at the crossroads of
      cellular networks; such signaling proteins have multiple partners that bind
      through shared binding sites. This review highlights these shared binding sites,
      and describes research to suggest that partners binding at these sites could at
      least partly interact via different energetically dominant 'hot-spot' residues.
      The data also indicate that, despite dynamic changes in the distribution of the
      conformational ensembles, the hot-spot conformations are retained in their pre
      organized states.

PMID- 20812145
TI  - Modulation of the vasopressin system for the treatment of CNS diseases.
AB  - Vasopressin (also known as arginine vasopressin [AVP]) is a small cyclic peptide
      that acts at the V1a, V1b and V2 GPCRs to regulate a wide range of physiological
      functions, including vasoconstriction, smooth muscle contractility, response to
      stress, and excretion of water and sodium via the kidney. The potential
      therapeutic applications of AVP receptor ligands have prompted significant
      interest in this target within the pharmaceutical research community, and several
      small-molecule drugs targeting the AVP receptor have reached the market, mainly
      for cardiovascular indications. The development of AVP receptor modulators for
      the treatment of CNS indications has proven more challenging, and is the focus of
      this review. The regulatory role of AVP on the hypothalamic-pituitary-adrenal
      (HPA) axis suggests potential uses for AVP receptor modulators in various CNS
      indications, including depression, anxiety and post-traumatic stress disorder.
      Several clinical trials of V1a and V1b receptor antagonists in CNS indications
      have been conducted, but none of these drugs have reached the market. In recent
      years, the discovery of the key role of AVP in modulating complex social
      behaviors has provided a unique opportunity to understand the physiological
      mechanisms of social interactions. Ultimately, the ongoing research in this field
      may enable the development of treatments to alleviate the social deficits
      associated with conditions such as autism and schizophrenia. Given the large
      unmet medical need in these areas, a renewed interest in the field of CNS
      penetrant AVP receptors modulators is expected.

PMID- 20812146
TI  - Emerging targets for hematological malignancies.
AB  - Molecularly targeted therapies have been increasingly incorporated into standard
      treatment regimens for the majority of hematological malignancies. To increase
      the efficacy of the next generation of drugs, research efforts have been aimed at
      identifying molecular defects specific to leukemic cells. A significant
      therapeutic opportunity is represented by the possibility of selectively
      eradicating the leukemic stem cell pool. This review focuses on new insights
      regarding oncogenetic mechanisms in hematological malignancies and related
      possible druggable targets, including the pathways leading to leukemic stem cell
      maintenance and the specific approaches used to eliminate them.

PMID- 20812147
TI  - Mechanisms of distribution and targeting of neuronal ion channels.
AB  - The discovery and development of pharmaceutical drugs targeting ion channels is
      important for treating a variety of medical conditions and diseases. Ion channels
      are expressed ubiquitously throughout the body, and are involved in many basic
      physiological processes. Neuronal ion channels are particularly appealing drug
      targets, and recent advances in screening ion channel function using optical
      based and electrophysiological technologies have improved drug development in
      this field. Moreover, methods for the discovery of peptide-based neurotoxins and
      other natural products have proven useful in the pharmacological assessment of
      ion channel structure and function, while also contributing to the identification
      of lead molecules for drug development.

PMID- 20812148
TI  - The potential for caspases in drug discovery.
AB  - Caspases are a family of proteases that are involved in the execution of
      apoptosis and the inflammatory response. A plethora of diseases occur as a result
      of the dysregulation of apoptosis and inflammation, and caspases have been
      targeted as a therapeutic strategy to halt the progression of such diseases.
      Hundreds of peptide and peptidomimetic inhibitors have been designed and tested,
      but only a few have advanced to clinical trials because of poor drug-like
      properties and pharmacological constraints. Although much effort has been focused
      on inhibiting caspases, there are many diseases that result from a decrease in
      apoptosis, thus activating procaspases could also be a viable therapeutic
      strategy. To this end, recent efforts have focused on the design of procaspase-3
      activators. This review highlights the current progress in the rational design of
      both specific and pan-caspase inhibitors, as well as procaspase-3 activators.

PMID- 20812149
TI  - Small-molecule PARP modulators--current status and future therapeutic potential.
AB  - PARP-1 inhibitors have emerged as a promising therapeutic class of compounds, and
      numerous PARP inhibitors, including iniparib (BiPar Sciences Inc/sanofi-aventis),
      olaparib (AstraZeneca plc), veliparib (Abbott Laboratories), PF-1367338 (Pfizer
      Inc), MK-4827 (Merck & Co Inc) and CEP-9722 (Cephalon Inc), have advanced into
      clinical trials. Several additional inhibitors are expected to enter clinical
      trials within the next year. Early investigations with PARP-1 inhibitors involved
      non-oncological indications, but development has since progressed to focus
      primarily on oncology, for use both as single chemotherapeutic agents in specific
      patient populations (eg, BRCA-deficient) and as combination therapies with
      various chemotherapeutics. This review focuses on new developments in lead
      clinical PARP inhibitors, recent disclosures of new inhibitors and the potential
      use of PARP-1 inhibitors in new disease settings.

PMID- 20812150
TI  - Orthosteric- and allosteric-induced ligand-directed trafficking at GPCRs.
AB  - Many orthosteric agonists differentially activate downstream effectors of GPCRs.
      Such defined induction of signaling has strongly supported the hypothesis termed
      'ligand-directed trafficking of receptor signaling' (LDTRS). More recently,
      subtype-selective GPCR activators, such as allosteric agonists and positive
      allosteric modulators, have also exhibited the capacity to activate specific
      signaling pathways. Based on this finding, it may be possible to achieve ligand
      specific receptor active states that optimize the biological responses specific
      to GPCRs. This review discusses recent studies in which both orthosteric and
      allosteric compounds have been demonstrated to induce LDTRS.

PMID- 20812152
TI  - The role of the mTOR pathway in regulating food intake.
AB  - mTOR is a principal effector of nutrient action, integrating nutritional inputs
      from glucose, amino acids and fatty acids, as well as growth factor and hormonal
      signals. The mTOR signaling pathway plays a vital role in regulating cell growth
      and proliferation, and has been studied extensively in a variety of metabolic and
      cancer models. However, only recently has the mTOR signaling pathway become
      implicated in the regulation of food intake. This review focuses on recent
      studies describing the role of hypothalamic and gastric mTOR signaling in
      suppressing food intake, and discusses the potential mechanisms through which
      this regulation occurs.

PMID- 20812151
TI  - The role of tau kinases in Alzheimer's disease.
AB  - A principal feature of the progression of Alzheimer's disease (AD) is the
      appearance of aberrant phosphorylation of the microtubule-associated protein tau
      in the brains of affected individuals. Significant research efforts have been
      directed at identifying the kinases involved in this process, as well as
      developing pharmacological agents to inhibit these molecules. This review focuses
      on recent developments in both the physiological and pathological effects of tau
      phosphorylation, and the contribution of phosphorylation to tau toxicity and
      pathological progression in AD. The evolving concepts of the roles tau plays in
      cellular biology, and the mechanisms by which phosphorylation regulates tau
      function, is reshaping the framework for the development of therapeutics
      targeting tau to treat AD.

PMID- 20812153
TI  - Current understanding and importance of histone phosphorylation in regulating
      chromatin biology.
AB  - The core histones H2A, H2B, H3 and H4, undergo various post-translational
      modifications, such as acetylation, methylation and phosphorylation. Core histone
      phosphorylation has roles in several biological responses, including
      transcription, mitosis, DNA repair and apoptosis. Histone phosphorylation may
      disrupt chromatin structure and/or provide a 'code' for the recruitment or
      occlusion of non-histone chromosomal proteins to chromatin. Among the better
      characterized histone phosphorylation events are the phosphorylation of H3 at
      Ser10 and Ser 28, and the phosphorylation of the H2A variant H2A.X at Ser139.
      Much remains to be learned about the function of the many other core histone
      phosphorylation events in chromatin. This review provides an overview of the
      biological roles of core histone phosphorylation in mammalian cells.

PMID- 20812155
TI  - [Gastric neuroendocrine tumors in a woman with systemic lupus erythematosus].
AB  - HISTORY AND CLINICAL FINDINGS: A 56-year-old woman presented with pronounced
      petechia. She complained about recurrent fever and night sweat for two weeks,
      having felt unwell during the past years. INVESTIGATIONS: Laboratory examinations
      showed thrombocytopenia, leukopenia and considerably elevated liver enzymes.
      Antinuclear antibodies and antibodies against double-stranded DNA were positive.
      Sonography showed a slightly enlarged liver with multiple surrounding lymph
      nodes, splenomegaly and chronic-atrophic thyroiditis. Gastroscopy revealed
      several polypes which were immunohistochemically classified as neuroendocrine
      tumors (NET). DIAGNOSIS, TREATMENT AND COURSE: Systemic lupus erythematosus (SLE)
      with involvement of several organs was diagnosed and high doses of steroids were
      given. The steroid was then gradually reduced and changed to azathioprine. The
      NET were removed endoscopically. CONCLUSION: Neuroendocrine tumors are rare and
      localised to the stomach in only 2 - 4 %. Only three cases of gastric NET in the
      context of SLE with autoimmune gastritis have been reported so far in the
      literature.

PMID- 20812157
TI  - [Pulmonary necrotizing sarcoid granulomatosis in a patient with primary biliary
      cirrhosis].
AB  - HISTORY AND ADMISSION FINDINGS: A 53-year-old woman presented with recurrent
      episodes of cough and non-specific pulmonary symptoms. For many years she had
      been known to have primary biliary cirrhosis. INVESTIGATIONS: The chest X-ray
      showed multiple pulmonary nodules. Microbiological examination did not detect any
      pathogen and transbronchial biopsy of the pulmonary nodules failed to provide a
      diagnosis. Histology of a surgical lung biopsy showed interstitial inflammation,
      vasculitis and non-caseating granulomas. TREATMENT AND COURSE: The findings
      indicated necrotizing sarcoid granulomatosis. During oral corticoid therapy the
      pulmonary nodules regressed within a few weeks. The patient has remained free of
      pulmonary symptoms. CONCLUSION: Pulmonary necrotizing sarcoid granulomatosis is a
      rare condition to consider in the differential diagnosis of pulmonary nodules.
      Because of the histological findings and its benign course it resembles
      sarcoidosis.

PMID- 20812156
TI  - [Arthritis of the atlanto-axial joint with inflammatory neck pain as a primary
      manifestation of seronegative rheumatoid arthritis].
AB  - HISTORY AND ADMISSION FINDINGS: A 68-year-old woman with known degenerative joint
      disease suffered from increasing neck pain. Physical examination revealed
      painfully restricted movement of the cervical spine. INVESTIGATIONS: Erythrocyte
      sedimentation rate and C-reactive protein were increased. Tests for rheumatoid
      factors, antinuclear, anti-citrullinated protein and anti-neutrophil cytoplasmic
      antibody were negative. Cervical spine x-ray showed osteochondrosis with
      partially bridging spondylosis at C5/C6, but there was no atlanto-axial
      dislocation. Magnetic resonance imaging (MRI) revealed bone marrow edema and
      hyperintensity of the odontoid process, but there were no indications of fissures
      or fracture lines. TREATMENT AND COURSE: These findings indicated seronegative
      rheumatoid arthritis, with predominantly active atlanto-axial arthritis. After
      methotrexate and prednisolone had been administered the symptoms improved rapidly
      and inflammatory parameters returned to normal. Three months later no atlanto
      axial arthritis was seen at MRI. CONCLUSION: Rheumatoid arthritis involving the
      atlanto-axial region should be considered in patients with persisting neck pain
      and signs of inflammation.

PMID- 20812158
TI  - [64-year-old patient with efflorescences on the upper and lower legs].

PMID- 20812159
TI  - [Sepsis with acral necrosis in a patient with Sharp syndrome - case 8/2010].
AB  - HISTORY AND ADMISSION FINDINGS: We report on a patient with Sharp-Syndrome who
      was referred to our emergency department with sepsis. In addition, the patient
      showed acral necrosis, particularly of the distal phalanges of the hands and of
      the tip of the nose. INVESTIGATIONS: Laboratory analyses showed an elevation of
      the inflammatory parameters (C-reactive protein elevation, leukocytosis).
      Furthermore, procalcitonin and the D-dimers were increased, antithrombin III,
      however, was decreased. The thoracic/abdominal computed tomography (CT) showed
      bilateral inferior lobe pneumonia with concomitant pleural effusions. As a
      secondary diagnostic finding the thoracic/abdominal CT and the abdominal
      ultrasound showed a markedly reduced size of the spleen. Finally, bacteria
      (Streptococcus pneumoniae) were found in the blood of the patient. DIAGNOSIS,
      TREATMENT AND COURSE: We diagnosed pneumococcal sepsis with disseminated
      intravasal coagulation and acral necrosis caused by pneumonia. The immune status
      was impaired due to immunosuppressive therapy (prednisolon and azathioprin) and
      functional asplenism. The patient was stabilized with antibiotic treatment,
      hydration, and drotrecogin (protein C). Transiently catecholamin treatment and
      oxygen substitution were necessary. Alprostadil was used to treat acral
      circulatory disorder. CONCLUSIONS: This case report shows the importance of
      consequent screening for organ manifestations in autoimmune diseases. In
      particular, this case report highlights the relevance of prophylactic vaccination
      in patients with autoimmune diseases, primarily those with autosplenectomy.
      Furthermore, this article gives a short overview about the pathogenesis, the
      diagnostic criteria of the Sharp-syndrome. The frequencies of organ involvement
      and the treatment options are also discussed.

PMID- 20812160
TI  - [The current debate on lowering LDL cholesterol with ezetimibe].

PMID- 20812161
TI  - [Laparoscopic "fast-track" sigmoidectomy for diverticulitis disease in Germany.
      Results of a prospective quality assurance program].
AB  - BACKGROUND AND OBJECTIVE: The natural course of sigmoid colon diverticulitis
      during conservative therapy and the assessment of the perioperative morbidity
      after sigmoid colon resection are differently evaluated by surgeons and
      gastroenterologists. The "fast-track" rehabilitation accelerates the
      reconvalescence and reduces the rate of postoperative general complications after
      colorectal surgery. The results of the laparoscopic "Fast-track" sigmoidectomy
      should be examined within a quality assurance program to better evaluate the
      perioperative risks following surgical management of diverticulitis. PATIENTS AND
      METHODS: A prospective data collection within the voluntary quality assurance
      program "fast-track" Kolon II was performed. All participating clinics agreed on
      a multimodal, evidence-based standard perioperative treatment in terms of a "fast
      track" rehabilitation for elective operations for sigmoid diverticulitis.
      RESULTS: Data from 846 patients undergoing laparoscopic "fast-track" sigmoid
      colon resection in 23 surgical departments in Germany were collected and
      evaluated. The mean age of the patients was 63 years (range 23 - 91). 203
      patients (24 %) had severe co-morbidities (ASA classification III - IV). A
      conversion to conventional open surgery was necessary in 51 cases (6 %).
      Complications occurred in 93 patients (11 %). 76 patients suffered a surgical
      complication (8.9 %) and 32 patients (3.8 %) a general complication. Two patients
      died postoperatively due to multi-organ failure following anastomotic leaks. The
      patients took solid food in median on day 1 after surgery (range, 0 - 5) and
      passed stool on day 2 (range, 0 - 22). Predefined discharge criteria (free of
      pain on oral medication, normal oral feeding, stool) were met on day 4 (range, 1 
      58) and the patients were discharged on day 7 (range, 3 - 72). The 30-day re
      admission rate was 3.9 %. CONCLUSION: Patients undergoing laparoscopic "fast
      track" sigmoidectomy had a low rate of general complications and had a rapid
      reconvalescence with a short postoperative in-patient treatment as documented in
      a german quality assurance program.

PMID- 20812162
TI  - [Psoriasis as an independent risk factor for development of coronary artery
      disease].
AB  - Psoriasis is a chronic inflammatory dermatosis with a relapsing course. The best
      known comorbidity is psoriatic arthritis. In daily clinical practise it is well
      known, that patients with psoriasis show more often classic cardiovascular risk
      factors such as obesity, Diabetes mellitus, hyperlipoproteinemia, hypertension,
      nicotine abuse often presenting as Metabolic Syndrome and suffer more often from
      coronary heart disease than patients without psoriasis. This could be
      demonstrated in numerous clinical and epidemiologic studies. In the last few
      years there is increasing evidence for psoriasis being an independent
      cardiovascular risk factor despite of concomitant classic risk factors. This
      review summarizes the current state of research and discusses possible common
      immunopathogenetic mechanisms.

PMID- 20812163
TI  - ["The Lantus case": and yet it does move (or not?)].

PMID- 20812164
TI  - [Arthralgias during menopause: pathogenic connections].

PMID- 20812165
TI  - Low sampling rates bias outcomes from the Wingate test.
AB  - The purpose of this work was to apply a simple method for acquisition of power
      output (PO) during the Wingate Anaerobic Test (WAnT) at a high sampling rate (
      S(R)) and to compare the effect of lower S(R) on the measurements extracted from
      the PO. 26 male subjects underwent 2 WAnTs on a cycle ergometer. The reference PO
      was calculated at 30 Hz as a function of the linear velocity, the moment of
      inertia and the frictional load. The PO was sampled at 0.2, 0.5, 1, 2 and 5 Hz.
      Both the peak (16.03+/-2.22 W.kg (-1)) and mean PO (10.34+/-1.01 W.kg (-1))
      presented lower relative values when the S(R) was lower. Peak PO was attenuated
      by 0.29-42.07% for decreasing sampling rates, resulting in different values for
      0.2 and 1 Hz ( P<0.001). When the S(R) was 0.2 Hz, the time to peak was delayed
      by 53.81% ( P<0.001) and the fatigue index was attenuated by 22.12% ( P<0.001).
      In conclusion, due to the differences achieved here and the fact that the peak
      flywheel frequency is around 2.3 Hz, we strongly recommend that the PO be sampled
      at 5 Hz instead of 0.2 Hz in order to avoid biased errors and misunderstandings
      of the WAnT results.

PMID- 20812166
TI  - [The role of ceruloplasmin in the differential diagnosis of neuropsychiatric
      disorders].
AB  - The blue copper protein ceruloplasmin has been of interest to psychiatrists for
      decades following Heilmeyer's observation of elevated serum copper levels in
      schizophrenic patients. Immunoturbidimetry, however, does not yield elevated
      serum ceruloplasmin concentrations in schizophrenia while ceruloplasmin-related
      oxidase activity appears to be elevated in patients with schizophrenia and
      reduced in patients with Alzheimer's disease. Low serum concentrations of immuno
      turbidimetrically measured ceruloplasmin, and of oxidase activity, are typical of
      Wilson's disease, Menkes' disease, and aceruloplasminemia, three familial
      neurodegenerative disorders of pronounced variability, with regard to both
      genotype and phenotype. Especially patients with Wilson's disease may exhibit
      behavioural symptoms only over a long period. Heterozygous carriers of Wilson's
      disease and aceruloplasminaemia may have low serum ceruloplasmin concentrations;
      they will not develop somatic symptoms, but the significance of these carrier
      states, or of "hypoceruloplasminaemia", with regard to mental disorders is
      unknown.

PMID- 20812167
TI  - [Attachment disorders in the postpartum period].

PMID- 20812168
TI  - [A secret pioneer in psychiatric inquiry].

PMID- 20812172
TI  - [Apropos of a case of giant choledochocele].

PMID- 20812173
TI  - [Fertility and inflammatory bowel diseases].
AB  - BACKGROUND: Data concerning fertility during inflammatory bowel disease are
      insufficient and sometimes contradictory. The aims of this review are to precise
      the impact of inflammatory bowel disease on fertility. METHODS: Literature
      review. RESULTS: The risk of infertility seems to be raised at one under group of
      patients and made to intervene several factors of which, in particular for the
      Crohn's disease, the activity of the disease and the psychological impact leads
      by this chronic disorder. The decrease of the fertility, as very feminine as
      male, during the ulcerative colitis is essentially bound to the surgery. Data
      concerning the impact of various therapeutic used during inflammatory bowel
      disease on the fertility are very insufficient and interest especially male
      fertility.

PMID- 20812174
TI  - [Upper urinary tract infections in adults: about 261 episodes].
AB  - BACKGROUND: Upper urinary tract infections are frequent. Escherichia coli is the
      main pathogen identified from community acquired infections. AIM: We aim to study
      epidemiologic, clinical and bacterial features of this infection. METHODS: We
      identified 261 episodes that occurred in 241 patients. They were 213 females and
      48 males aged of 48.75 years. Enterobacteriaceae were the main pathogens isolated
      in 93.5%: E. coli in 73.3% and Klebsiella pneumoniae in 15.3%. E. coli
      sensitivity was of 30% for amoxicillin, 98% for cefotaxim, 96% for gentamicin,
      90% for ciprofloxacin and 56% for co-trimoxazole. Anterior antibiotic use was
      associated with low E. coli sensitivity mainly with fluoroquinolones (96 vs 77%)
      and co-trimoxazole (62 vs 43%). This enhances the role of antibiotic pressure on
      the resistance emergence. CONCLUSION: the reasonable use of antibiotics is
      necessary to limit resistance extent.

PMID- 20812175
TI  - [Occupational carpal tunnel syndrome: 27 cases].
AB  - BACKGROUND: Carpal tunnel syndrome is the most frequent of tunnel syndromes in
      the field of the professional sphere. It is related to repetitive movements of
      flexion-extension of the wrist and fingers or to a support on the heel of the
      hands. AIM: To determine the posts in a risk and to specify the modalities of
      guaranteed reimbursement of professional carpal tunnel syndrome. METHODS: A
      retrospective and descriptive study of 27 medical files of employees indemnified
      for professional carpal tunnel syndrome registered in the medical control
      services of the social security office in charge of medical insurance of Tunis
      and Sousse during a period of 10 years (1995-2004). RESULTS: There were 24 women
      and 3 men with the average age of 40 years all occupying posts in a risk. Their
      average time of service is 15 years. Tow-thirds of them work in the clothing and
      textile industry. The attack is bilateral in 13 cases. Nightly acroparaesthesia
      rules the clinical rate (44.44% of cases). Motor disorders are noted in the
      quarter of cases. The electromyogram had confirmed diagnosis in all of cases. The
      previous state study put in evidence the antecedent of carpal tunnel syndrome in
      5 cases and diabetes in one case. Twenty-one patients had profit of permanent
      partial incapacity with a rate varying from 3 to 25%. Five had got a transfer of
      working place and one stayed in the same post with a half-time work. CONCLUSION:
      The professional origin of carpal tunnel syndrome must be called up in front of
      an activity in a risk. The reparation is done according to picture 82 of
      occupational diseases.

PMID- 20812176
TI  - [Urinary tract infections in children following renal transplantation: a single
      center experience].
AB  - BACKGROUND: Urinary tract infection (UTI) is the most common complication after
      kidney transplantation and represents a potential life-threatening risk for the
      immunocompromised child. AIM: The aim of this report is to determinate incidence,
      risk factors, microbiologic features and evaluate the impact of this complication
      on graft outcome and patient mortality. METHODS: We performed a retrospective
      cohort study reviewing the medical records of 17 children from 38 who received a
      renal transplant in our center between January 1992 and june 2008 and who present
      an urinary tract infection. RESULTS: All patients received Lich-Gregoire
      implantation and insertion of double-J stunt. Antibioprophylaxis was not
      systematic. After a mean period of 6 years, 9 children (5+4) developed early UTI
      (during the first month after transplantation) and 5 (3+2) had late UTI. Three
      patients (2+1) with an indeterminate nephropathy developed early and late UTI.
      Causal agents are: E. Coli, Klebsiella Pneumoniae and Candida albicans. The
      further voiding cystourethrography showed a vesico-ureteral reflux on graft in 5
      cases. Among the 17 patients, 4 lost their graft and are actually on
      haemodialysis. CONCLUSION: The urinary tract infection represents the major
      complication after renal transplantation. Diagnosis ant treatment must be made
      early to avoid the loss of the graft.

PMID- 20812177
TI  - A3243G mitochondrial DNA mutation in Tunisian diabetic population.
AB  - BACKGROUND: An excess of maternal transmission of adult onset diabetes mellitus
      has been observed in the studied Tunisian patients, in fact, diabetic patients
      with affected mother are significantly more important than those with affected
      father (p< 10-6) There is increasing evidence that mtDNA mutations may be
      involved in this disease, since mitochondrial transmission offers a plausible
      explanation for a proportion of this maternal excess comparing to paternal
      transmission. AIM: The aim of the present study was to investigate the
      mitochondrial DNA involvement in the inheritance of diabetes in Tunisian
      population and to evaluate the frequency of substitution A3243G in these
      patients. METHODS: In the current study we investigated for the first time, the
      3243 mtDNA in 280 Tunisian diabetic patients. RESULTS: Results showed that the
      frequency of this substitution in tRNALeu is about 1.07%. This percentage is
      similar to those reported in Japanese, German and French populations.

PMID- 20812178
TI  - [Profile of a population of consultants in child psychiatry and access to care by
      gender].
AB  - BACKGROUND: Access to care in mental health is a fundamental element in the
      monitoring and care of children and adolescents. AIM: The objective of this work
      was to draw up the demographic and clinical characteristics of a population of
      consultants in child psychiatry and to investigate possible gender inequalities
      in access to care. METHODS: This is a descriptive cross-sectional study
      concerning a sample of 730 children and adolescents having consulted child
      psychiatry department in Tunis and Monastir during a period of 4 months (April
      July on 2006). Data were collected through a questionnaire administered to the
      relatives of patients consulting these various structures. RESULTS: 66 % of
      consulting were boys. In 55 % of cases, the mother, alone, accompanied the child
      to the consultation. The request of care emanated in the majority of the cases
      from parents and doctors. On average ran out 18 months before the first medical
      visit and 26 months before the first psychiatric consultation. Multiple medical
      consultations precede the meeting with the child psychiatrist. We have not found
      difference in the care of children and adolescents according to gender. Only the
      period preceding the first medical consultation for psychiatric symptoms was
      longer in girls compared to boys. CONCLUSION: Access to care structures was easy
      and even in cases of geographical remoteness parents did not seem to privilege
      boys over girls.

PMID- 20812179
TI  - The utility of alpha-methyl CoA racemase (P504S) expression as a marker of renal
      cell carcinomas.
AB  - BACKGROUND: Renal cell tumours are numerous and heterogeneous. Because of their
      clinicopathological heterogeneity, their accurate diagnosis may be challenging.
      In case of an equivocal diagnosis, immunohistochemistry may be a useful mean of
      diagnosis. Recently, alpha-methyl CoA racemase has been identified as a useful
      marker in kidney cancers. AIMS: Our objectives are to highlight the role of alpha
      methyl CoA racemase (AMACR) as a diagnostic marker in papillary renal carcinoma
      and to assess its utility in the other tumour types. METHODS: Aretrospective
      review was performed on 62 patients who were treated for renal tumours between
      January 1994 and November 2005. Immunoreactivity was evaluated with a qualitative
      manner. Positive AMACR staining was defined as a coarse dense cytoplasmic
      granularity. RESULTS: The 62 renal tumours were diagnosed as papillary tumours in
      22 cases, clear cell tumours in 18 cases, chromophobe carcinoma in 12 cases and
      oncocytoma in 10 cases among the 22 cases of papillary tumours, all the cases
      (100%) showed cytoplasmic immunoreactivity staining. 4 cases between the 18 clear
      cell carcinomas (22%) showed positivity with AMACR. The 12 cases of chromophobe
      carcinoma didn't express AMACR by immunohistochemistry. Only one case between the
      oncocytomas (1%) expressed AMACR. CONCLUSION: This study confirms the high
      sensitivity of AMACR for papillary renal cell carcinomas but we must keep in mind
      that weak focal AMACR staining could be present in other renal cell carcinomas.

PMID- 20812180
TI  - Hyperhomocysteinemia, C677T MTHFR polymorphism and ischemic stroke in Tunisian
      patients.
AB  - BACKGROUND: Hyperhomocysteinaemia has been identified as a strong risk factor for
      ischemic stroke (IS). A point mutation in methylene tetrahydrofolate reductase
      (MTHFR C677T) has been associated with increased plasma homocysteine (Hcy)
      levels. AIM: This preliminary study aimed to investigate whether
      hyperhomocysteinaemia and/or MTHFR C677T mutation are associated with ischemic
      stroke. METHODS: A case-control study including 50 consecutive patients with
      confirmed IS and 97 controls was performed. Fasting plasma homocysteine levels,
      MTHFR C677T genotypes were assessed. Other factors such as hypertension, obesity,
      dyslipidemia, diabetes mellitus, recurrent stroke tobacco and alcohol were
      investigated. RESULTS: Mean plasma homocysteine levels were significantly higher
      in IS patients than in controls (15.83+/-10.60) MUmol/L vs 13.78+/-6.29 MUmol/L,
      p=0.04), while no association of MTHFR C677T variant was observed even with
      homocysteine. The risk to develop ischemic stroke in hyperhomocysteinemic
      subjects was 2.4 times more than in subjects with normal Hcy levels (OR= 2.4; 95%
      CI: 1.13-5.06; p<0.05). CONCLUSION: Our findings suggest that high levels of
      homocysteine but not MTHFR C677T polymorphism represent risk factors for arterial
      ischemic stroke in Tunisian subjects.

PMID- 20812181
TI  - [Life conditions of Togolese doctors].
AB  - AIM: A study has been carried out by Togolese medical doctors in order to
      determine the perceived and the real life of their profession. METHODS: The
      study, which was transversal, has taken in account a sample of 52 medical doctors
      made on the basis of a cautious choice. Most of these medical doctors (15 general
      practitioners, 23 specialists and 14 hospitalo-universitaires) work in the
      medical cares centres of Lome. A sheet of survey has permitted the collection of
      demographic data and data relating to the medical studies and career. RESULTS:
      The 52 medical doctors included in the study (7 women, 45 men) were between 25
      and 59 years old; their age of getting their A-level was between 16 and 23 years
      old, and that of getting the doctorate diploma between 24 and 37. The length of
      professional experience stands between 8 months and 27 years. The marital status
      was specified by 47 of the 52 medical doctors: 13 single, one divorced, and 33
      married; 5 of the 7 women who took part in the survey were single and without any
      child. The love of the profession (65%), the social status it confers (37%) and
      the honour tied to the profession (27%) were the main motives of choosing the
      profession. The decision of doing medical studies was taken during secondary
      studies by 45 of the 52 persons. The faculty of medicine of Lome has been the
      study frame to general medicine studies of 35 persons (67%). The low payment
      (83%), the poverty of the patients (83%), the narrowness of the technical
      platform (79%), the insufficiency of cares structures in paramedical personnel
      (67%), the insufficiency of continuing education (60%), and the lack or
      insufficiency of drugs (58%) were the main problems encountered during their
      professional experience by the people questioned. 22 medical doctors (43%) have
      estimated that their profession has given them a particular social status. Only 8
      medical doctors have found that the real things they have gone trough in the
      profession matches with the idea they had, while 32 (62%) are ready to choose
      again the profession if they have to start everything. The little time spent with
      the family has been stated out by 36 medical doctors (69%), the social and family
      prestige that came out of it by 32 (62%), and the ability to control the health
      of one's family by 34 (65%). The psychological impact of the profession on the
      medical doctors questioned was dominated by the adoption of a philosophical
      attitude towards life. CONCLUSION: A better productivity of the Togolese medical
      doctors needs the improvement of their life conditions (adjustment of texts in
      force, revision of the salary scale), the renovation of the facilities, the
      modernization of the technical platform, the continuing education of the medical
      doctors and the reinforcement of the practical management of the patient on bed.

PMID- 20812182
TI  - First trimester diagnosis of Pallister-Killian syndrome in a fetus with
      suggestive abnormalities.
AB  - BACKGROUND: Pallister-Killian Syndrome is a rare, sporadic chromosomal disorder
      characterized by a tetrasomy 12p often in mosaic. It is only in 2000 that the
      first case of PKS was diagnosed in the first trimester further to an increased
      nuchal translucency. AIM: Report a new case. CASE REPORT: To our knowledge, we
      present the first case of early prenatal diagnosis of Pallister Killian Syndrome
      due to the presence of an increased nuchal translucency, a diaphragmatic hernia,
      a typical facial dysmorphism and a micromelia of a predominantly rhizomelic type
      . A chorionic cells biopsy showed a normal karyotype. The diagnosis was revealed
      on cytogenetic analysis of amniotic fluid sampling. CONCLUSION: The main
      ultrasound indicators of PKS seem to be: Hydramnios, congenital diaphragmatic
      hernia (CDH) and a micromelia of a rhizomelic type. The Hydrops fetalis, hygroma
      coli or increased nuchal translucency (INT), fetal overgrowth, ventriculomegaly
      and presence of a sacral appendix are less common. The amniocentesis with the
      study of the karyotype on amniotic cells is considered to be the gold standard
      for the diagnosis of PKS. A good morphological study during the first trimester
      in search of ultrasound abnormalities highly suggestive of PKS is able to direct
      the cytogenetic study.

PMID- 20812183
TI  - [Pseudo tumoral gastric amyloidosis: a case report].
AB  - BACKGROUND: Amyloidosis is an abnormal extracellular deposition of insoluble
      proteins, which is associated with an involvement of the gastrointestinal tract
      in 50 to 70% of cases. In primary amyloidosis (light chain amyloidosis),
      localized gastric involvement is a rare finding which can mimick malignancy. AIM:
      To elucidate the clinical, histological and therapeutic features of pseudo
      tumoral gastric amyloidosis via a rare report along with a review of related
      literatures. OBSERVATION: We report the case of a 56-year-old man, admitted with
      upper digestive outlet obstruction. Linitis plastica with lymph node involvement
      was suspected by gastroscopy, barium meal and endoscopic ultrasonography but was
      not confirmed by gastric biopsies. The patient was treated with total gastrectomy
      with lymph node dissection. Pathological examination demonstrated gastric and
      lymph nodes amyloidosis and no malignant tumor was found. CONCLUSION: We propose
      that amyloidosis should be considered in the differential diagnosis of gastric
      tumors.

PMID- 20812184
TI  - [Autoimmune hepatitis type 1 triggered by cytomegalovirus infection. One rare
      case report].
AB  - BACKGROUND: Autoimmune hepatitis is chronic and uncommon disease. The
      pathogenesis is a complex process. Several triggers for autoimmune hepatitis
      particularly viral herpesviridae infection, which may induce the development of
      autoimmunity in predisposed individuals. AIM: Report a new case. CASE REPORT: We
      report a case of 17-year- woman presented with autoimmune triggered by
      cytomegalovirus infection. Cytomegalovirus induced autoimmune hepatitis has not
      been reported previously. Evolution was favourable under antiviral treatment,
      corticosteroid and azathioprine.

PMID- 20812185
TI  - [Minor beta thalassemia masked by a hemoglobin A2 mutant].
AB  - BACKGROUND: The elevation of hemoglobin A2 (HbA2) is an essential criterion in
      the diagnosis of minor ss thalassemia. AIM: To report a case of minor ss
      thalassemia HbA2 with normal HbA2 rate. OBSERVATION: We report the case of ten
      years old boy, with hypochromic microcytic anemia, refractory to iron treatment.
      The study of hemoglobin (Hb) has revealed the presence of a minor abnormal
      fraction of Hb, amounted to 2.8%, associated with the presence of HbF and normal
      levels of HbA2. Family study revealed the presence of two Hb abnormalities (ss
      thalassemia trait and HbA2 mutant) transmitted to offspring in isolation or
      associated. The genotypic study confirmed the presence of minor, 0 thalassemia
      and a 0/00 gene mutation, causing a new mutant HbA2 named HbA2 Pasteur-Tunis
      [0/00 59(E3)LysgAsn(AAGgAAC)]. CONCLUSION: The presence of 0/00 mutant reduces
      HbA2 level and could hide ss thalassemia trait. Rigorous and methodical
      interpretation of phenotypic data is crucial to not overlook the presence of ss
      thalassemia trait, whose diagnosis is crucial for genetic counseling and prenatal
      diagnosis.

PMID- 20812186
TI  - [Liver neuroblastoma in an adult].

PMID- 20812187
TI  - [Gayet-Wernicke encephalopathy secondary to pregnant vomiting].

PMID- 20812188
TI  - [Malignant hypercalcemia with increased PTH].

PMID- 20812189
TI  - Malignant extra-adrenal pheochromocytoma--a diagnostic dilemma.

PMID- 20812190
TI  - [Abnormal intestinal permeability in children with autism].

PMID- 20812191
TI  - Germline HVR-II mitochondrial polymorphisms associated with breast cancer in
      Tunisian women.
AB  - A high incidence of somatic mtDNA polymorphisms has been reported in a wide
      variety of human cancers; some of them have been proposed as markers for the
      early detection of breast cancer. However, little attention has been paid to the
      potential of germline mitochondrial sequence variations as genetic risk factors
      for cancer. We performed a case-control study of 70 unrelated Tunisian women with
      breast cancer and 80 healthy age- and gender-matched blood donors, taking into
      account clinicopathological data, to evaluate germline polymorphism of
      mitochondrial HVR-II region as a genetic risk factor for breast cancer. Through
      direct sequencing, we detected 351 polymorphisms in controls and 248 variants in
      patients, with 47 and 39 segregating sites, respectively. In both groups, more
      than 50% of the polymorphisms were due to four variants: 315 ins C, 309 ins C,
      263 A>G, and 73 A>G. The HVR-II sequences were also classified into haplotypes on
      the basis of the polymorphisms. Fifty-nine different haplotypes were found, 20 of
      them shared between patients and controls. Both groups had specific haplotypes,
      18 in breast cancer patients and 21 in controls. Statistical analysis revealed a
      weak protective effect against breast cancer risk for two mitochondrial
      polymorphisms - 152 T>C (odds ratio (OR) = 0.33, 95% confidence interval (CI) =
      0.12-0.91) and 263 A>G (OR = 0.17, 95%CI = 0.06-0.47). In contrast, an increased
      risk of breast cancer was detected for the 315+C haplotype (OR = 11.66, 95%CI =
      1.44-252.23). We conclude that mitochondrial variants can affect breast cancer
      risk. More extensive studies, involving different types of cancer and patients
      with different genetic makeup, will be required to improve our understanding of
      the effects of germline mtDNA polymorphisms on carcinogenesis.

PMID- 20812192
TI  - Psychogenetics of Turner syndrome: an investigation of 28 subjects and respective
      controls using the Bender test and Piagetian scales.
AB  - Piagetian scales and the Bender visual motor gestalt test (BT) were applied to 28
      subjects with universal 45,X Turner syndrome (TS), and their respective controls,
      in order to investigate their cognitive performance. Dermatoglyphics were also
      analyzed to obtain clues concerning embryological changes that may have appeared
      during development of the nervous system and could be associated with cognitive
      performance of TS patients. Dermatoglyphic pattern distribution was similar to
      that reported in previous studies of TS individuals: ulnar loops in the digital
      patterns and finger ridge, a-b, and A'-d counts were more frequent, while arch
      and whorl patterns were less frequent compared to controls. However, we did not
      find higher frequencies of hypothenar pattern, maximum atd angle, and ulnarity
      index in our TS subjects, unlike other investigations. Furthermore, we found
      significant differences between TS and control T line index values. The BT scores
      were also lower in probands, as has been previously reported, revealing a
      neurocognitive deficit of visual motor perception in TS individuals, which could
      be due to an absence of, or deficiency in, cerebral hemispheric lateralization.
      However, TS subjects seemed to improve their performance on BT with age.
      Cognitive performance of the TS subjects was not significantly different from
      that of controls, confirming a previous study in which TS performance was found
      to be similar to that of the normal Brazilian population. There were significant
      correlations between BT scores and Piagetian scale levels with dermatoglyphic
      parameters. This association could be explained by changes in the common
      ectodermal origin of the epidermis and the central nervous system. TS subjects
      seem to succeed in compensating their spatial impairments in adapting their
      cognitive and social contacts. We concluded that genetic counseling should
      consider cognitive and psychosocial difficulties presented by TS subjects,
      providing appropriate treatment and orientation for them and their families.

PMID- 20812193
TI  - IGF-I gene polymorphism, but not its blood concentration, is associated with milk
      fat and protein in Holstein dairy cows.
AB  - We estimated the allele and genotype frequencies of IGF-I/SnaBI gene polymorphism
      and the concentration of this protein in Holstein dairy cows. We also examined
      the association with milk yield (305-day milk yield) and milk components (fat and
      protein percentage, and 305-day milk protein and fat yield). Blood IGF-I levels
      were measured and genotyping was performed on 250 Holstein cows of four different
      herds. In the association studies, traits of interest were analyzed using the GLM
      procedure of SAS; means of the IGF-I level among genotypes were compared by the
      LSMeans test. The AB and AA genotypes were the most (0.583-0.661) and least
      (0.083-0.192) frequent in the herds, respectively; the frequency of the BB
      genotype ranged from 0.201 to 0.333. The frequency of the A allele ranged from
      0.375 to 0.495, while the frequency of the B allele ranged from 0.504 to 0.625,
      being the dominant allele. The mean level of IGF-I was 107 +/- 22 ng/mL for all
      groups, without any significant correlation with the production traits.
      Association of IGF-I/SnaBI genotypes with percentage of fat and protein in the
      milk was relatively high (P < 0.1 and P < 0.05, respectively); the AB genotype
      was superior to AA and BB genotypes. We concluded that this marker should be
      considered for milk component selection in Holstein dairy cattle.

PMID- 20812194
TI  - The L55M polymorphism of paraoxonase-1 is a risk factor for rheumatoid arthritis.
AB  - Paraoxonase-1 (PON1) is a high-density lipoprotein-associated enzyme that
      exhibits antioxidant and antiatherogenic activities. We examined a possible
      association between T172A (L55M) and T(-107)C polymorphisms and rheumatoid
      arthritis. These polymorphisms were determined in 88 rheumatoid arthritis
      patients and 78 healthy subjects, using the tetra-amplification refractory
      mutation system-PCR method. The prevalence of the PON1 55MM genotype was
      significantly greater among rheumatoid arthritis patients (17%) when compared to
      control subjects (5.2%) (odds ratio (OR) = 3.75; 95% confidence interval (CI) =
      1.87-11.8, P = 0.025). In addition, the M allele was more frequent in rheumatoid
      arthritis patients (40%) than in healthy subjects (24.7%) (OR = 1.997; 95%CI =
      1.243-3.210, P = 0.005). There were no significant differences in the -107C/T
      polymorphism in the promoter sequence of PON1 between rheumatoid arthritis and
      normal subjects (chi(2) = 0.861, P = 0.650). In conclusion, the PON1 55MM
      genotype is a risk factor for rheumatoid arthritis.

PMID- 20812195
TI  - Combining ability of tropical and temperate inbred lines of popcorn.
AB  - In Brazil, using combining ability of popcorn genotypes to achieve superior
      hybrids has been unsuccessful because the local genotypes are all members of the
      same heterotic group. To overcome this constraint, 10 lines (P(1) to P(10)) with
      different adaptations to tropical or temperate edaphoclimatic environments were
      used to obtain 45 F(1) hybrids in a complete diallel. These hybrids and three
      controls were evaluated in two environments in Rio de Janeiro State. Grain yield
      (GY), popping expansion (PE), plant height (PH), ear height (EH), and days to
      silking (FL) were evaluated in randomized complete blocks with three
      replications. Significant differences between genotypes (P <or= 0.05) were
      detected for GY, PE and EH. General combining ability was significant for EH, PH,
      PE, and GY, and specific combining ability was significant only for PE and GY.
      The most promising inbred lines that improved GY were P(3) and P(4), unlike P(8),
      P(9) and P(10), which improved PE, and P(2), which improved both PE and GY. The
      additive effects were much more important for PE than for GY. The hybrid
      combinations gave positive estimates of heterosis for GY but not for PE.

PMID- 20812196
TI  - A novel polymorphism of the MYPN gene and its association with meat quality
      traits in Bos taurus.
AB  - Myopalladin (MYPN) is a multifunctional protein that maintains sarcomeric
      integrity and regulates Z-line structure. It is an important candidate gene for
      meat quality selection through marker-assisted selection. Using PCR-RFLP
      technology, we discovered a single-nucleotide polymorphism (SNP) (A1795G in exon
      9) of the MYPN gene. Allele frequencies of this SNP were investigated and
      evaluated by the chi(2) test in 660 cattle populations in China; only the Nanyang
      population was not in Hardy-Weinberg equilibrium. Gene heterozygosity, effective
      allele number and polymorphism information content of the bovine MYPN locus in
      seven populations varied from 0.3888 to 0.4998, 1.6360 to 1.9992, and 0.3132 to
      0.3749, respectively. We also looked for a potential association of this SNP with
      ultrasound traits in 399 individuals and found a significant effect on the
      ultrasound loin-muscle area. Meat quality traits were analyzed in another 61
      Qinchuan individuals to analyze associations with genotype. Animals with the
      genotype GG had higher mean values for loin-eye area (P < 0.05) and water-holding
      capacity (P < 0.01) than those with AA or AG genotypes. We conclude that this SNP
      of the MYPN gene has potential as a genetic marker for meat quality traits in
      cattle reproduction and breeding.

PMID- 20812198
TI  - Morpho-functional modifications of human neutrophils induced by aqueous cigarette
      smoke extract: comparison with chemiluminescence activity.
AB  - Cigarette smoking plays an important role as a cause of morbidity and mortality
      in humans, involving respiratory, cardiovascular, digestive and reproductive
      systems. Tobacco smoke contains a large number of molecules, some of which are
      proven carcinogens. Although not fully understood, polymorphonuclear leukocytes
      seem to play a crucial role in the mechanisms by which tobacco smoke compounds
      are implicated in smoke-related diseases. In this paper the effects of an aqueous
      cigarette smoke extract on the expression of adhesion molecules of
      polymorphonuclear leukocytes together with the changes in the cell morphology
      have been related to the chemiluminescence activity. The results obtained show
      that polymorphonuclear leukocytes treated with aqueous cigarette smoke extract
      are significantly impaired, as suggested by the changes of chemiluminescence
      activity, of membrane receptors (CD18, CD62), myeloperoxidase expression and of
      cell morphology. Altogether the present data indicate that treated
      polymorphonuclear leukocytes are ineffectively activated and therefore unable to
      phagocytize zymosan particles.

PMID- 20812199
TI  - Development of chemiluminescence method for determination of 10
      hydroxycamptothecin based on luminol-[Ag(HIO6)2]5- reaction in alkaline solution.
AB  - A novel chemiluminescence (CL) method was developed for the determination of 10
      hydroxycamptothecin(HCPT) based on the CL reaction between [Ag(HIO6)2]5- and
      luminol in alkaline solution. CL emission of Ag(III) complex-luminol in alkaline
      medium was very different from that in acidic medium. A possible mechanism of
      enhanced CL emission was suggested. The enhanced effect of HCPT on CL emission of
      the [Ag(HIO6)2]5--luminol system was found. The enhanced degree of CL emission
      was proportional to HCPT concentration. The effect of the reaction conditions on
      CL emission was examined. Under optimal conditions, the limit of detection was
      6.5 * 10-9 g mL-1. The proposed method was applied for the determination of HCPT
      in real samples with the recoveries of 93.2-109% with the RSD of 1.7-3.3%.

PMID- 20812200
TI  - Determination of anthocyanins in the urine of patients with colorectal liver
      metastases after administration of bilberry extract.
AB  - Anthocyanins possess cancer chemopreventive properties in preclinical models.
      Their clinical pharmacology is only poorly understood. In this pilot study,
      anthocyanins and their metabolites were analysed in the urine of two patients
      with colorectal liver metastases. They received a single dose of 1.88 g
      standardized bilberry extract (mirtoselect) via either nasogastric or nasojejunal
      tube intra-operatively during liver resection. HPLC-MS/MS and HPLC-UV analysis
      showed there were more anthocyanins and metabolites in the urine of the patient
      who received mirtoselect via the stomach than via the jejunum. This result is
      consistent with information obtained in rodents which suggests the stomach is the
      predominant site for anthocyanin absorption.

PMID- 20812201
TI  - Compounds having thiourea moiety as derivatization reagents in liquid
      chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS):
      synthesis of derivatization reagents for carboxylic acids.
AB  - The derivatization reagents for carboxylic acids, N-(Pyridin-3
      yl)hydrazinecarbothioamide, N-[4-(dimethylamino)phenyl]hydrazinecarbothioamide, 1
      (2-aminoethyl)-3-(pyridin-3-yl)thiourea, 1-(2-aminoethyl)-3-[4
      (dimethylamino)phenyl]thiourea and 4-(2-aminoethyl)-N-phenylpiperazine-1
      carbothioamide were synthesized. These reagents reacted with carboxylic acids at
      60 degrees C for 45 min in the presence of the condensation reagents. The
      generated derivatives were favorably separated on the reversed-phase column and
      sensitively detected by electrospray ionization tandem mass spectrometry. These
      reagents enhanced the electrospray ionization response of the analyte and
      generated a particular product ion efficiently by collision-induced dissociation,
      and thus they were suitable for MS/MS detection.

PMID- 20812202
TI  - HPLC method development and validation of cytotoxic agent phenyl-heptatriyne in
      Bidens pilosa with ultrasonic-assisted cloud point extraction and
      preconcentration.
AB  - Extraction and pre-concentration of a bioactive marker compound, phenyl-1,3,5
      heptatriyne from Bidens pilosa, prior to HPLC has been demonstrated using both
      organic and ecofriendly solvents. Non-ionic surfactants, viz. Triton X-100,
      Triton X-114 and Genapol X-80, were used for extraction. No back-extraction or
      liquid chromatographic steps were required to remove the target phytochemical
      from the surfactant-rich extractant phase. The optimized cloud point extraction
      procedure has been shown to be a potentially useful methodology for the
      preconcentration of the target analyte, with a preconcentration factor of 4-99.
      Moreover, the method is simple, sensitive, rapid and consumes lesser solvent than
      traditional methods. An isocratic chromatographic separation and quantitation was
      accomplished on a C(18) column with acetonitrile-acidified aqueous as mobile
      phase at a flow rate of 1.0 mL/min, UV detection at 254 nm and specificity with
      photo diode-array detector (PDA) and MS. Under the optimum experimental
      conditions recovery was satisfactory (99.18-100.33%) without interference from
      the surfactant. The method seems to be reliable with intraday precision and
      interday precision below 2.0%. Good linearity was obtained in the working range
      from 7.5 to 30 ug/mL with correlation coefficient >0.99. The limits of detection
      and quantitation were 1.84 and 6.13 ug/mL, respectively. The method was validated
      following international guidelines and successfully applied for quantitative
      assays of cytotoxic compound phenyl-1,3,5-heptatriyne in Bidens pilosa.

PMID- 20812203
TI  - Thermophilic laccase from xerophyte species Opuntia vulgaris.
AB  - Two laccase temperature isoforms capable of oxidizing phenolic compounds to
      quinones were isolated and purified to homogeneity from the cladodes of the
      xerophyte species Opuntia vulgaris. These catalytically active proteins exhibit
      apparent molecular masses of 137 and 90 kDa. Under reducing conditions, both
      isoforms yielded a subunit molecular mass of 43 kDa, suggesting that the enzyme
      is a multimer of the 43 kDa subunit. The 137 kDa isoform when heated at 80
      degrees C for 3 min generated three polypeptide bands on activity stained
      polyacrylamide gels exhibiting 137, 90 and 43 kDa molecular forms. All isoforms
      of the enzyme exhibited an optimum pH of 10 when 2,6-dimethoxyphenol was used as
      a substrate. The optimum temperature of the 137 kDa enzyme form was noted to be
      80 degrees C and that of the 90 kDa enzyme form was 70 degrees C. Denaturation
      kinetics of both the laccase isoforms carried out at their respective optimum
      temperatures for 30 min exhibited enzyme activity in excess of their t(1/2)
      values throughout the assay period. The K(m) for the 137 kDa form was determined
      to be 2.2 +/- 0.3 mm and the V(max) was 2.8 +/- 0.2 IU/mL. These high temperature
      stable laccase isoforms having alkaline pH optima can find significant industrial
      use.

PMID- 20812204
TI  - Metabonomic study on women of reproductive age treated with nutritional
      intervention: screening potential biomarkers related to neural tube defects
      occurrence.
AB  - Nutritional intervention is effective in reducing the risk of neural tube defects
      (NTDs). To determine the effects of nutritional supplementation on human
      metabolism, a metabonomic study was carried out on 96 women of reproductive age.
      Subjects with nutritional intervention were given fortified wheat flour
      (containing folic acid, vitamin B1, vitamin B2, ferric sodium edetate and zinc
      oxide) for 8 months. Serum metabolic fingerprinting was detected via
      ultraperformance liquid chromatography in tandem with time-of-flight mass
      spectrometry (UPLC-TOF MS), and data acquired was processed by multivariate
      statistical analysis. The result revealed a significant difference between the
      control and intervention group. Twenty potential biomarkers, including fructose 6
      phosphate, sphingosine 1-phosphate, docosahexaenoic acid and hexadecanoic acid,
      were located and identified by the accurate mass measurement of TOF MS. These
      compounds are believed to be functionally related to anti-oxidative competence in
      vivo. In conclusion, metabonomics study is a valuable approach in exploring the
      effect mechanism of nutritional intervention on NTD prevention.

PMID- 20812205
TI  - An LC-MS method for simultaneous determination of nine ginsenosides in rat plasma
      and its application in pharmacokinetic study.
AB  - A sensitive and reliable LC-ESI-MS method for simultaneous determination of nine
      ginsenosides (Rh(1), Rg(2), Rg(1), Rf, Re, Rd, Rc, Rb(2) and Rb(1)) in rat plasma
      was developed and validated using saikosaponin A as an internal standard. The
      samples were extracted by solid-phase extraction. Chromatographic separation was
      carried out on a Hypersil Gold C(18) column (100 * 2.1 mm, 5 um) by stepwise
      gradient elution with water (0.1% formic acid, v/v) and acetonitrile as the
      mobile phase. Detection was determined by selective ion monitoring mode using
      electrospray ionization in the negative ion mode. Good linearity over the
      investigated concentration ranges was observed with the values of r higher than
      0.9900. The intra- and inter-day precisions were all no more than 15% and the
      average recoveries varied from 71.8 to 91.7%. This quantitative measurement was
      successfully applied to a pharmacokinetic study of Yi-Qi-Fu-Mai injection.

PMID- 20812206
TI  - Rapid ultraperformance liquid chromatography-tandem mass spectrometry method for
      quantification of oxcarbazepine and its metabolite in human plasma.
AB  - A rapid and sensitive ultraperformance liquid chromatography tandem mass
      spectrometry assay was developed for the simultaneous analysis of oxcarbazepine
      and its main metabolite in human plasma. The assay involves a simple solid-phase
      extraction procedure of 0.3 mL of human plasma and analysis was performed on a
      triple-quadrupole tandem mass spectrometer in multiple reaction monitoring mode
      via electrospray ionization. Separation was achieved on an Acquity UPLCTM BEH C18
      column (50 * 2.1 mm, i.d., 1.7 um) with isocratic elution at a flow-rate of 0.25
      mL/min and imipramine was used as the internal standard. The standard calibration
      curve was linear over the range 9.580-5070.205 ng/mL for oxcarbazepine (OXC) and
      19.444-10290.800 ng/mL for 10,11-dihydro-10-hydroxycarbamazepine (MHD), expressed
      by the linear correlation coefficient r2, which was better than 0.995 for OXC and
      MHD. The intra- and inter-day precision and accuracy of the quality control
      samples were within 10.0%. The recoveries were 81.0, 89.6 and 66.6% for OXC, MHD
      and imipramine, respectively. The total run time was 1.5 min only for each
      sample, which makes it possible to analyze more than 350 samples per day.

PMID- 20812207
TI  - Development and validation of UPLC tandem mass spectrometry assay for separation
      of a phase II metabolite of ramipril using actual study samples and its
      application to a bioequivalence study.
AB  - In this paper, we present a validated UPLC-MS/MS assay for determination of
      ramipril and ramiprilat from human plasma samples. The assay is capable of
      isolating phase II metabolites (acylglucornides) of ramipril from in vivo study
      samples which is otherwise not possible using conventional HPLC conditions. Both
      analytes were extracted from human plasma using solid-phase extraction technique.
      Chromatographic separation of analytes and their respective internal standards
      was carried out using an Acquity UPLC BEH C(18) (2.1 * 100 mm), 1.7 um column
      followed by mass spectrometric detection using an Waters Quattro Premier XE. The
      method was validated over the range 0.35-70.0 ng/mL for ramipril and 1.0-40.0
      ng/mL for ramiprilat.

PMID- 20812208
TI  - A rapid and simple assay for lamotrigine in serum/plasma by HPLC, and comparison
      with an immunoassay.
AB  - Monitoring serum/plasma concentrations of lamotrigine may be useful under certain
      circumstances. An HPLC column packed with strong cation-exchange (SCX)-modified
      microparticulate silica together with a 100% methanol eluent containing an ionic
      modifier permits direct injection of sample extracts. An HPLC-UV method developed
      using this principle for the measurement of serum/plasma lamotrigine is simple,
      sensitive and selective. The analysis time is less than 5 min. Intra- and inter
      assay precision and accuracy meet acceptance criteria, and sample stability, and
      potential interferences from other compounds have been evaluated. There was good
      agreement with consensus mean results from external quality assessment samples (n
      = 32). Analysis of patient samples (n = 115) using the HPLC method and the
      Seradyn QMS(r) Lamotrigine immunoassay showed that the immunoassay over-estimated
      lamotrigine by 21% on average.

PMID- 20812210
TI  - Synthesis and characterization of 1- and 2-cinnamoyloxyacetonaphthones.
AB  - The synthesis of 1- and 2-cinnamoyloxyacetonaphthones was achieved in one step
      using hydroxyl acetonaphthones and substituted cinnamic acids in the presence of
      a catalytic amount of phosphoroxychloride. Structural characterization was
      accomplished using high-resolution nuclear magnetic resonance (NMR) spectroscopy.
      Chemical shifts of the compounds were compared and the change in the chemical
      shifts relative to electron-donating and -withdrawing groups is presented.
      Introduction of a thiophene ring instead of phenyl-substituted analogs caused
      shielding of the olefinic proton.

PMID- 20812211
TI  - Heteronuclear dipolar decoupling in liquid-crystal NMR using supercycled SW(f)
      TPPM sequences.
AB  - Heteronuclear dipolar decoupling is an essential requirement for extracting
      structural information from the (13)C NMR spectra of liquid crystals. Efficient
      schemes for heteronuclear dipolar decoupling in such systems are formulated here
      by supercycling SW(f)-TPPM, a sequence introduced recently for this purpose in
      rotating solids. These sequences are compared with two other commonly used
      decoupling schemes in liquid-crystal NMR, SPINAL-64 and SW(f)-TPPM, by analyzing
      the intensities of various resonances in the proton decoupled (13)C spectrum of
      the liquid-crystal 4-n-pentyl-4'-cyanobiphenyl (5CB). The effectiveness of the
      decoupling programs with respect to experimental parameters such as RF field
      strength, decoupler offset frequency and phase angle is also presented.

PMID- 20812209
TI  - Expression of pleiotrophin in the prostate is androgen regulated and it functions
      as an autocrine regulator of mesenchyme and cancer associated fibroblasts and as
      a paracrine regulator of epithelia.
AB  - BACKGROUND: Androgens and paracrine signaling from mesenchyme/stroma regulate
      development and disease of the prostate, and gene profiling studies of inductive
      prostate mesenchyme have identified candidate molecules such as pleiotrophin
      (Ptn). METHODS: Ptn transcripts and protein were localized by in situ and
      immunohistochemistry and Ptn mRNA was quantitated by Northern blot and qRT-PCR.
      Ptn function was examined by addition of hPTN protein to rat ventral prostate
      organ cultures, primary human fetal prostate fibroblasts, prostate cancer
      associated fibroblasts, and BPH1 epithelia. RESULTS: During development, Ptn
      transcripts and protein were expressed in ventral mesenchymal pad (VMP) and
      prostatic mesenchyme. Ptn was localized to mesenchyme surrounding ductal
      epithelial tips undergoing branching morphogenesis, and was located on the
      surface of epithelia. hPTN protein stimulated branching morphogenesis and stromal
      and epithelial proliferation, when added to rat VP cultures, and also stimulated
      growth of fetal human prostate fibroblasts, prostate cancer associated
      fibroblasts, and BPH1 epithelia. PTN mRNA was enriched in patient-matched normal
      prostate fibroblasts versus prostate cancer associated fibroblasts. PTN also
      showed male enriched expression in fetal human male urethra versus female, and
      between wt male and ARKO male mice. Transcripts for PTN were upregulated by
      testosterone in fetal human prostate fibroblasts and organ cultures of female rat
      VMP. Ptn protein was increased by testosterone in organ cultures of female rat
      VMP and in rat male urethra compared to female. CONCLUSIONS: Our data suggest
      that in the prostate Ptn functions as a regulator of both mesenchymal and
      epithelial proliferation, and that androgens regulate Ptn levels.

PMID- 20812213
TI  - Laboratory maintenance of Mycobacterium abscessus.
AB  - Mycobacterium abscessus, is an emerging, rapidly growing pathogen, with the
      ability to cause chronic lung disease. This unit covers background information
      and laboratory maintenance procedures for this bacterium, including growth in
      liquid and on solid medium. It also contains recommendations concerning long-term
      strain storage. M. abscessus is a Biosafety Level 2 organism, and the required
      safety measures are also discussed.

PMID- 20812212
TI  - Structure elucidation of two new bisbenzylisoquinoline alkaloids and NMR
      assignments of the alkaloids from the fruits of Tiliacora racemosa.
AB  - Besides three known biphenyldibenzodioxinbisbenzylisoquinoline alkaloids, two
      novel alkaloids of the same group have been isolated from the fruits of Tiliacora
      racemosa. The structures of these new compounds designated tiliaimine and
      nordinklacorine were established on the basis of 1D and 2D NMR spectroscopy,
      including COSY, TOCSY, ROESY, HMBC and HSQC experiments. Preliminary
      antibacterial activity studies on the known compounds (tiliarine, 2'
      nortiliacorinine, 2'-nortiliacorine) from the fruits of the plant showed strong
      activity against three bacterial strains viz. Escherichia coli strain VT3
      (Verotoxigenic E.coli), Staphylococcus aureus ATCC 25923 and Bacillus subtilis
      ATCC 6623 but were inactive against the strains Vibrio cholerae O1 (NB2) and
      Pseudomonas aeruginosa ATCC 15442.

PMID- 20812214
TI  - Genetic manipulation of Mycobacterium abscessus.
AB  - This unit covers genetic manipulation protocols for M. abscessus, including
      nucleic acid extraction (plasmid DNA, genomic DNA, and RNA), transformation, and
      a recombineering mutagenesis method. M. abscessus is a Biosafety Level 2 (BSL-2)
      bacterium, and working considerations are also discussed.

PMID- 20812215
TI  - Laboratory maintenance of Streptomyces species.
AB  - This unit includes general protocols for the laboratory maintenance of
      Streptomyces species, including growth in liquid media, growth on solid agar, and
      short- and long-term storage. Considerations for the handling of Streptomyces
      species and the morphology of the bacteria are also reviewed.

PMID- 20812216
TI  - Human cytomegalovirus: propagation, quantification, and storage.
AB  - Human cytomegalovirus (HCMV) is the largest and perhaps the most structurally
      complex member of the family of human herpesviruses. It is the prototypic virus
      of the beta-herpesvirus subfamily. As with other cytomegaloviruses, HCMV is
      exquisitely species specific and undergoes lytic replication only in cells of
      human origin. In addition, its replication is limited almost entirely to primary
      cells and a limited number of transformed cell lines. Together with its prolonged
      replicative cycle of approximately 48 hr, the propagation and quantification of
      HCMV can present technical challenges. In this brief set of protocols, the
      propagation of laboratory strains of HCMV and their quantitation is described. In
      a third series of protocols, the concentration and gradient purification of HCMV
      for more specialized downstream applications is described.

PMID- 20812217
TI  - Cell-based hepatitis C virus infection fluorescence resonance energy transfer
      (FRET) assay for antiviral compound screening.
AB  - Hepatitis C virus (HCV) affects an estimated 3% of the population and is a
      leading cause of chronic liver disease worldwide. Since HCV therapeutic and
      preventative options are limited, the development of new HCV antivirals has
      become a global health care concern. This has spurred the development of cell
      based infectious HCV high-throughput screening assays to test the ability of
      compounds to inhibit HCV infection. This unit describes methods that may be used
      to assess the in vitro efficacy of HCV antivirals using a cell-based high
      throughput fluorescence resonance energy transfer (FRET) HCV infection screening
      assay, which allows for the identification of inhibitors that target HCV at any
      step in the viral life cycle. Basic protocols are provided for compound screening
      during HCV infection and analysis of compound efficacy using an HCV FRET assay.
      Support protocols are provided for propagation of infectious HCV and measurement
      of viral infectivity.

PMID- 20812218
TI  - Laboratory growth and maintenance of Haemophilus influenzae.
AB  - Haemophilus influenzae is a non-spore forming, non-motile, pleomorphic Gram
      negative coccobacilli. H. influenzae is a strict human pathogen that can cause a
      variety of systemic and localized infections, depending on the strain. The three
      Basic Protocols in this unit will describe how to culture and prepare H.
      influenzae for the use in biological studies of the organism.

PMID- 20812219
TI  - A quick diagnostic test for NMR receiver gain compression.
AB  - Modern NMR spectrometers require receivers to work within their linear ranges to
      maintain high fidelity line shape and peak integration. For better sensitivity,
      the receiver gain has to be optimized to detect dilute analytes; however, gain
      compression needs to be avoided. Here, we explore if and how linear receiver
      performance can be achieved for a couple of representative gain settings on a
      spectrometer. In the case of slight receiver gain compression, not only will the
      peak integral be attenuated but a very small line-shape change can also be
      observed. Hence, we can resort to resonance integration and line-shape analysis
      for gain compression diagnosis. As such, NMR signals, regardless of their
      observed amplitude difference in frequency domain, can be accurately compared in
      quantitative analysis.

PMID- 20812220
TI  - Overcoming extreme obesity with robotic surgery.
AB  - BACKGROUND: Obesity is often associated with endometrial cancer and has posed a
      challenge in surgical management. Complications such as wound breakdown,
      respiratory challenges, cardiac complications and difficult intubations are
      associated with obesity. For the patient with uterine cancer, surgery is
      necessary for staging, control of symptoms and cure. With the advent of the da
      Vinci(TM) intuitive robot, alternative surgical options can now be offered to
      these patients. While surgery is the principal modality for the treatment and
      management of uterine cancer, the morbidly obese patient faces increased
      complications and longer postoperative recovery. As studied in the LAP2,
      comparable outcomes have been noted in laparotomy vs laparoscopic surgery.
      Recently, minimally invasive surgery has been refined with the advent of the da
      Vinci robotic system. Applying a minimally invasive technique further enhanced
      with the da Vinci robotic system, a total laparoscopic hysterectomy with
      bilateral salpingo-oophorectomy was performed on a patient with a BMI of 98.
      METHODS: A 35 year-old G0 woman with a BMI of 98 presented with heavy vaginal
      bleeding and anaemia. She was diagnosed with endometrioid adenocarcinoma of the
      uterus, FIGO grade 1. She was treated with a robotically assisted total
      laparoscopic hysterectomy and bilateral salpingo-oophorectomy. RESULTS: Her
      postoperative course was uncomplicated and she was discharged home on post
      operative day 1. CONCLUSIONS: Since obesity is a significant risk factor for
      endometrial cancer and the prevalence of obesity is increasing, developing
      surgical techniques to appropriately manage these patients is important.
      Minimally invasive surgery, specifically with robotic assistance, has increased
      the possibilities of performing minimally invasive surgery in morbidly obese
      women. It allows navigation around anatomical barriers and decreases the fatigue
      experienced by the surgeons. With the increasing obesity of our population and
      the high prevalence of uterine cancer, further advancement of equipment,
      anaesthesia and surgical techniques to accommodate the larger patient while
      decreasing complications have yet to be standardized.

PMID- 20812221
TI  - Significant prognostic factor of immunohistochemical HER-2 expression using
      initial prostate biopsy specimens with M1b prostate cancer.
AB  - BACKGROUND: We examined whether human epidermal growth factor-2(HER-2)
      overexpression could be a useful marker of outcome after hormone therapy in
      patients with M1b prostate cancer (PC). SUBJECTS AND METHODS: The subjects were
      102 patients who were diagnosed with M1b PC at Aichi Medical University Hospital.
      HER-2 expression was determined by immunohistochemical (IHC) staining using
      initial needle biopsy specimens for diagnosis. The results were classified into
      four grades (0, 1+, 2+, 3+), and scores of 1+ or greater were considered
      overexpression and defined as positive. RESULTS: The results showed a rating of 0
      in 72 subjects, 1+ in 10, 2+ in 14, and 3+ in 6; 30 subjects (29.4%) were
      classified as HER-2 positive. Comparison of clinical data of HER-2 positive and
      negative subjects obtained at baseline revealed many of the subjects with high
      grade tumors by Gleason score were HER-2 positive (P = 0.030). The prostate
      specific antigen (PSA) relapse was observed in 76 subjects and cause-specific
      death occurred in 44. A significant difference was observed only in the item HER
      2 (negative vs. positive) by multivariate Cox proportional hazard analysis. The 5
      year PSA relapse-free rate was 0% in subjects with HER-2 positive (26/30), and
      43.9% in subjects with HER-2 negative (50/72, P = 0.0192). The 5-year cause
      specific survival rate was 40.9% in subjects with HER-2 positive (30/102), and
      67.3% in subjects with HER-2 negative (72/102, P = 0.0301). CONCLUSION: HER-2
      overexpression as determined by IHC staining using needle biopsy specimens for
      diagnosis with M1b PC is a significant prognostic factor for PSA relapse after
      hormone therapy and unfavorable outcome.

PMID- 20812222
TI  - Tumor cell group via phospholipase A2 is involved in prostate cancer development.
AB  - BACKGROUND: Prostate cancer (PCa) is one of the most common malignancies among
      men in the United States. Further understanding of the molecular mechanisms
      underlying PCa tumorigenic development is critical for advancing treatment
      strategies for PCa. The role of Group VIA phospholipase A2beta (iPLA2beta) in
      cancers has recently emerged. However, the biological functions of iPLA2beta in
      PCa development have been minimally investigated and only in vitro studies have
      been reported. METHODS: We tested the role of iPLA2beta in host cells using an
      iPLA2beta deficient mouse model and the role of iPLA2beta in tumor cells by
      comparing the proliferation, migration, and invasion in vitro and tumorigenesis
      in vivo. CONCLUSIONS: iPLA2beta deficiency did not affect tumor development in
      C57BL/6 mice injected with syngeneic PCa cell line TRAMP-C1P3 in any of three
      models (subcutaneous, orthotopic, or intratibia injection) tested, suggesting
      that host cell iPLA2beta is not required for PCa tumorigenesis and metastasis. In
      contrast, when iPLA2beta was down-regulated in TRAMP-C1P3 cells, cell
      proliferation was reduced in vitro and tumor growth was suppressed in vivo
      compared to control cells. In particular, iPLA2beta was required for
      lysophosphatidic acid (LPA)-induced migration and invasion in TRAMP-C1P3 cells.
      We compared human and mouse PCa cells and showed that they shared high
      similarities in LPA-stimulated effects and signaling pathways. LPA stimulated
      cell migration and/or invasion via a PI3K-dependent pathway. Together, our
      results suggest that the tumor cell iPLA2beta-LPA axis may represent a novel
      target for PCa.

PMID- 20812223
TI  - Cell-cycle regulators cdk2ap1 and bicalutamide suppress malignant biological
      interactions between prostate cancer and bone cells.
AB  - INTRODUCTION: We examined whether the novel cell-cycle regulator cdk2-associated
      protein 1 (p12(cdk2ap1) or cdk2ap1), recently shown to regulate prostate cancer
      cell cycle and apoptosis, could have the capacity to reduce invasiveness and/or
      reduce malignant biological interactions between prostate cancer and bone cells.
      We also examined whether combining two cell-cycle arrest stimuli, cdk2ap1 plus
      bicalutamide (or casodex, CDX), could help enhance inhibition of prostate cancer
      cell phenotypes. METHODS: We stably expressed cdk2ap1 in prostate cancer cell
      lines using lentiviral vectors, as well as several different co-culture assays to
      quantify cellular invasion, migration, and the effect of the treatments on
      interaction with the bone microenvironment. RESULTS: We have determined that
      cdk2ap1 can further augment the effects of CDX on cell-cycle arrest, growth
      inhibition, and cellular invasion. Using a coculture model, we observed that
      either cdk2ap1 or cdk2ap1/CDX combination were able to reduce chemotaxis towards
      osteoblasts, and also reduce the osteoblastic proliferative response to prostate
      cancer. Also modified by cdk2ap1 and CDX were several signaling pathways
      associated with prostate cancer/bone crosstalk mechanisms involved in prostate
      cancer progression. CONCLUSIONS: These results suggest that either cdk2ap1 or the
      cdk2ap1/CDX combination hold promise in regulating prostate cancer growth and
      malignant phenotypes, and potentially also in reducing procarcinogenic
      interactions with a bone microenvironment model, restoring malignant phenotypes
      and signaling to a more benign state.

PMID- 20812224
TI  - Effect of 25-hydroxyvitamin D status on serological response to influenza vaccine
      in prostate cancer patients.
AB  - BACKGROUND: Epidemiologic data suggest that there is an association between
      vitamin D deficiency and influenza infection. We conducted a prospective
      influenza vaccination study to determine the influence of vitamin D status on
      serological response to influenza vaccine in prostate cancer (CaP) patients.
      METHODS: During the 2006-2007 influenza season, CaP patients treated at Roswell
      Park Cancer Institute were offered vaccination with the trivalent influenza
      vaccine (Fluzone(r), 2006-2007) and sera collected for hemagglutination
      inhibition (HI) assay titers before and 3 months after vaccination. Response to
      vaccination was defined as >=1:40 titer ratio or a fourfold increase in titer at
      3 months, against any of the three strains. Serum 25-hydroxyvitamin D (25-D3)
      levels were measured using DiaSorin 125I radioimmunoassay kits. RESULTS: Thirty
      five patients with CaP participated in the study. Median baseline 25-D3 level was
      44.88 ng/ml (range: 9.16-71.98 ng/ml) Serological response against any of the
      three strains was noted in 80%. There was a significant effect of baseline 25-D3
      level when tested as a continuous variable in relation to serological response (P
      = 0.0446). All patients in the upper quartile of 25-D3 level responded by
      mounting a serological response (P = 0.0344). None of the other baseline
      variables (age, race, chemotherapy status, or white cell count) had an effect on
      serological response. CONCLUSIONS: In this study in CaP patients, a replete
      vitamin D status was associated with more frequent serological response to
      influenza vaccine.

PMID- 20812225
TI  - Prostatectomy restores the maturation competence of blood dendritic cell
      precursors and reverses the abnormal expansion of regulatory T lymphocytes.
AB  - OBJECTIVE: To verify the presence of deviated dendritic cell (DC) precursors and
      of suppressor lymphocytes (Treg) in tumor bearing prostate cancer (PCa) patients
      and to monitor the corrective effect of tumor ablation. METHODS: Monocytes
      isolated from the blood of patients before and 1 month after prostatectomy were
      allowed to reach complete maturation (mDC) ex vivo in a clinical grade two-step
      process. T-regulatory cells were identified in the lymphocyte cell fraction by
      the CD4(+)CD25(high)FoxP3(+)/CD4(+)CD25(high)CD127(low/-) phenotype. RESULTS:
      Despite loss of the monocytes marker CD14, cytokine-matured DCs of tumor bearing
      patients expressed lower levels of the costimulatory molecule CD80 and of the
      maturation markers CD83 and CCR7 compared to mDC of normal subjects (NS, P =
      0.001, 0.001, and 0.008, respectively). Prostatectomy restored CD80, CD83, and
      CCR7 expression to values not different from those of NS (P = 0.15, 0.60, and
      0.71) and significantly higher than those of the pre-surgery state (CD83, P =
      0.0003 and CCR7, P = 0.002). The frequency of Tregs, identified as either CD4 +
      CD25(high)FoxP3(+) or CD4(+)CD25(high)CD127(low/-), was significantly higher in
      pre-surgery patients than in NS (P = 0.0001 and 0.0003) and significant recovery
      of the CD4(+)CD25(high)CD127(low/-) (P = 0.0005) was observed after surgery.
      CONCLUSIONS: The presence of defective DC precursors and suppressor lymphocytes
      in the tumor-bearing, but not tumor-free stage, positions the latter as the ideal
      setting for clinical success of PCa vaccine therapy.

PMID- 20812226
TI  - Synthesis and antioxidant activity of new pyridines containing gallate moieties.
AB  - Pyridines containing the galloyl moiety have been prepared utilizing 4-acetyl
      pyrogallol. In addition, fused pyridines were synthesized from the obtained
      pyridines via further chemical transformations. The results indicated that
      compound 4a showed stronger DPPH scavenging activity than the other compounds,
      and the scavenging effect decreased in the following order 4a > t-BHQ > 2a > 2b >
      3a > 3b > 4b. Accordingly, other antioxidant assays were conducted for 4a. The
      results suggested that compound 4a could be a good antioxidant candidate. The
      absence of mortality of rats receiving 5000 mg/kg body weight of 4a as single
      oral dose may indicate that it could be a safe antioxidant and may be used for
      further studies.

PMID- 20812227
TI  - Bone sialoprotein deficiency impairs osteoclastogenesis and mineral resorption in
      vitro.
AB  - Bone sialoprotein (BSP) and osteopontin (OPN) belong to the small integrin
      binding ligand N-linked glycoprotein (SIBLING) family, whose members interact
      with bone cells and bone mineral. Previously, we showed that BSP knockout (BSP(-/
      ) ) mice have a higher bone mass than wild type (BSP(+/+) ) littermates, with
      very low bone-formation activity and reduced osteoclast surfaces and numbers.
      Here we report that approximately twofold fewer tartrate-resistant acid
      phosphatase (TRACP)-positive cells and approximately fourfold fewer osteoclasts
      form in BSP(-/-) compared with BSP(+/+) spleen cell cultures. BSP(-/-)
      preosteoclast cultures display impaired proliferation and enhanced apoptosis.
      Addition of RGD-containing proteins restores osteoclast number in BSP(-/-)
      cultures to BSP(+/+) levels. The expression of osteoclast-associated genes is
      markedly altered in BSP(-/-) osteoclasts, with reduced expression of cell
      adhesion and migration genes (alphaV integrin chain and OPN) and increased
      expression of resorptive enzymes (TRACP and cathepsin K). The migration of
      preosteoclasts and mature osteoclasts is impaired in the absence of BSP, but
      resorption pit assays on dentine slices show no significant difference in pit
      numbers between BSP(+/+) and BSP(-/-) osteoclasts. However, resorption of mineral
      coated slides by BSP(-/-) osteoclasts is markedly impaired but is fully restored
      by coating the mineral substrate with hrBSP and partly restored by hrOPN coating.
      In conclusion, lack of BSP affects both osteoclast formation and activity, which
      is in accordance with in vivo findings. Our results also suggest at least some
      functional redundancy between BSP and OPN that remains to be clarified.

PMID- 20812228
TI  - Preparation of a stationary phase with s-triazine ring embedded group for
      reversed phase high-performance LC.
AB  - This paper describes the synthesis and chromatographic evaluation of a new polar
      embedded stationary phase, which utilized 2,4,6-trichloro-1,3,5-triazine as the
      spacer. The resulting materials were characterized by elemental analysis, IR, and
      solid-state (13)C NMR. Empirical test mixtures were utilized to evaluate the
      column, and showed that it had good performance for basic compounds and high
      selectivity for polyaromatic hydrocarbons. Moreover, the novel stationary phase
      has unique property, especially in the separation of "homologous alkaloids" from
      natural products.

PMID- 20812229
TI  - Preparation and characterization of phosphatidylcholine-coated zirconia-magnesia
      stationary phase for artificial membrane chromatography.
AB  - Immobilized artificial membrane chromatography stationary phase was prepared by
      coating soybean phosphatidylcholine (PC) on zirconia-magnesia micro-particles.
      The stability and chromatographic properties were investigated and compared with
      the PC-coated silica chromatography stationary phase prepared by the same method.
      PC-coated zirconia-magnesia chromatography stationary phase was more stable than
      the silica especially on resisting organic solvents. Hydrophobic action was the
      main factor for the retention of analyte on the new artificial membrane
      chromatography stationary phase, and electrostatic interaction had some
      contribution to retention. In addition, the special interaction between analyte
      and matrix affected retention greatly. Basic solutes were appropriate to be
      analyzed on PC-coated zirconia-magnesia stationary phase and acidic solutes were
      appropriate to be done on the silica one. Hence, the two different matrices
      artificial membrane stationary phases were perfectly complementary.

PMID- 20812230
TI  - Selectivity of calixarene-bonded silica phases in HPLC: Description of special
      characteristics with a multiple term linear equation at different methanol
      concentrations.
AB  - Retention and selectivity characteristics of different calixarene-, resorcinarene
      and alkyl-bonded stationary phases are examined by analyzing a set of test
      solutes covering the main interactions (hydrophobic, steric, ionic, polar) that
      apply in HPLC. Therefore Dolan and Snyder's multiple term linear equation has
      been adapted to fit the properties of calixarene-bonded columns. The obtained
      parameters are used to describe retention and selectivity of the novel
      Caltrex((r)) phases and to elucidate underlying mechanisms of retention. Here,
      differences of stationary phase characteristics at different methanol
      concentrations in the mobile phases are examined. Both selectivity and retention
      were found to depend on the methanol content. Differences of these dependencies
      were found for different stationary phases and interactions. The differences
      between common alkyl-bonded and novel calixarene-bonded phases increase with
      increasing methanol content.

PMID- 20812231
TI  - Antitags: nanostructured tools for developing SERS-based ELISA analogs.

PMID- 20812232
TI  - Influences of task complexity, object location, and object type on hand selection
      in reaching in left and right-handed children and adults.
AB  - The effects of task complexity, object location, and object type on reaching
      behavior were examined. Two hundred ninety-two right-handed and 38 left-handed
      participants (grouped into five age groups) were asked to pick up or pick up and
      use objects in different regions of peripersonal space. It was found that
      individuals used their nonpreferred-hand more often in contralateral space than
      at the midline position. Using an object resulted in significantly more preferred
      hand reaches than picking up an object. Furthermore, task complexity, object
      location, and object type interacted with each other depending upon age group and
      hand preference.

PMID- 20812233
TI  - Intraoperative assessment of sentinel lymph nodes in breast cancer.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) reduces the morbidity of axillary
      clearance and is the standard of care for patients with clinically node-negative
      breast cancer. The ability to analyse the sentinel node during surgery enables a
      decision to be made whether to proceed to full axillary clearance during primary
      surgery, thus avoiding a second procedure in node-positive patients. METHODS:
      Current evidence for intraoperative sentinel node analysis following SLNB in
      breast cancer was reviewed and evaluated, based on articles obtained from a
      MEDLINE search using the terms 'sentinel node', 'intra-operative' and 'breast
      cancer'. RESULTS AND CONCLUSION: Current methods for evaluating the sentinel node
      during surgery include cytological and histological techniques. Newer
      quantitative molecular assays have been the subject of much recent clinical
      research. Pathological techniques of intraoperative SLNB analysis such as touch
      imprint cytology and frozen section have a high specificity, but a lower and more
      variably reported sensitivity. Molecular techniques are potentially able to
      sample a greater proportion of the sentinel node, and could have higher
      sensitivity.

PMID- 20812235
TI  - Chitin induces upregulation of B7-H1 on macrophages and inhibits T-cell
      proliferation.
AB  - Chitin is a highly abundant glycopolymer, which serves as structural component in
      fungi, arthropods and crustaceans but is not synthesized by vertebrates. However,
      vertebrates express chitinases and chitinase-like proteins, some of which are
      induced by infection with helminths suggesting that chitinous structures may be
      targets of the immune system. The chitin-induced modulations of the innate and
      adaptive immune responses are not well understood. Here, we demonstrate that
      intranasal administration of OVA and chitin resulted in diminished T-cell
      expansion and Th2 polarization as compared with OVA administration alone. Chitin
      did not promote nor attenuate Th2 polarization in vitro. Chitin-exposed
      macrophages inhibited proliferation of CD4(+) T cells in a cell-cell contact
      dependent manner. Chitin induced upregulation of the inhibitory ligand B7-H1 (PD
      L1) on macrophages independently of MyD88, TRIF, TLR2, TLR3, TLR4 and Stat6.
      Inhibition of T-cell proliferation was largely dependent on B7-H1, as the effect
      was not observed in cocultures with cells from B7-H1-deficient mice.

PMID- 20812234
TI  - Human mucosal leishmaniasis: neutrophils infiltrate areas of tissue damage that
      express high levels of Th17-related cytokines.
AB  - Mucosal leishmaniasis (ML) is characterised by severe tissue destruction. Herein,
      we evaluated the involvement of the IL-17-type response in the inflammatory
      infiltrate of biopsy specimens from 17 ML patients. IL-17 and IL-17-inducing
      cytokines (IL-1beta, IL-23, IL-6 and TGF-beta) were detected by
      immunohistochemistry in ML patients. IL-17(+) cells exhibited CD4(+), CD8(+) or
      CD14(+) phenotypes, and numerous IL-17(+) cells co-expressed the CC chemokine
      receptor 6 (CCR6). Neutrophils, a hallmark of Th17-mediated inflammation, were
      regularly detected in necrotic and perinecrotic areas and stained positive for
      neutrophil elastase, myeloperoxidase and MMP-9. Taken together, these
      observations demonstrate the existence of Th17 cells in ML lesions associated
      with neutrophils in areas of tissue injury and suggest that IL-17 is involved in
      ML pathogenesis.

PMID- 20812236
TI  - Targeting of LcrV virulence protein from Yersinia pestis to dendritic cells
      protects mice against pneumonic plague.
AB  - To help design needed new vaccines for pneumonic plague, we targeted the Yersinia
      pestis LcrV protein directly to CD8alpha(+) DEC-205(+) or CD8alpha(-) DCIR2(+) DC
      along with a clinically feasible adjuvant, poly IC. By studying Y. pestis in
      mice, we could evaluate the capacity of this targeting approach to protect
      against a human pathogen. The DEC-targeted LcrV induced polarized Th1 immunity,
      whereas DCIR2-targeted LcrV induced fewer CD4(+) T cells secreting IFN-gamma, but
      higher IL-4, IL-5, IL-10, and IL-13 production. DCIR-2 targeting elicited higher
      anti-LcrV Ab titers than DEC targeting, which were comparable to a protein
      vaccine given in alhydrogel adjuvant, but the latter did not induce detectable T
      cell immunity. When DEC- and DCIR2-targeted and F1-V+ alhydrogel-vaccinated mice
      were challenged 6 wk after vaccination with the virulent CO92 Y. pestis, the
      protection level and Ab titers induced by DCIR2 targeting were similar to those
      induced by F1-V protein with alhydrogel vaccination. Therefore, LcrV targeting to
      DC elicits combined humoral and cellular immunity, and for the first time with
      this approach, also induces protection in a mouse model for a human pathogen.

PMID- 20812238
TI  - DX5(+)CD4(+) T cells modulate cytokine production by CD4(+) T cells towards IL-10
      via the production of IL-4.
AB  - CD4(+) Th cells play a critical role in orchestrating the adaptive immune
      response. Uncontrolled Th1 responses are implicated in the pathogenesis of
      autoimmune diseases. T cells with immune-modulatory properties are beneficial for
      inhibiting such inflammatory responses. Previously we demonstrated that
      repetitive injections of immature DC induce expansion of DX5(+)CD4(+) T cells,
      which upon adoptive transfer show potent regulatory properties in murine collagen
      induced arthritis as well as in delayed-hypersensitivity models. However, their
      regulatory mechanism remains to be defined. Here, we analyzed the effect of
      DX5(+)CD4(+) T cells on other CD4(+) T cells in vitro. Although proliferation of
      naive CD4(+) T cells upon antigenic triggering was not altered in the presence of
      DX5(+)CD4(+) T cells, there was a striking difference in cytokine production. In
      the presence of DX5(+)CD4(+) T cells, an IL-10-producing CD4(+) T-cell response
      was induced instead of a predominant IFN-gamma-producing Th1 response. This
      modulation did not require cell-cell contact. Instead, IL-4 produced by
      DX5(+)CD4(+) T cells was primarily involved in the inhibition of IFN-gamma and
      promotion of IL-10 production by CD4(+) T cells. Together, our data indicate that
      DX5(+)CD4(+) T cells modulate the outcome of Th-responses by diverting Th1
      induction into Th responses characterized by the production of IL-10.

PMID- 20812237
TI  - Memory B cells from a subset of treatment-naive relapsing-remitting multiple
      sclerosis patients elicit CD4(+) T-cell proliferation and IFN-gamma production in
      response to myelin basic protein and myelin oligodendrocyte glycoprotein.
AB  - Recent evidence suggests that B- and T-cell interactions may be paramount in
      relapsing-remitting MS (RRMS) disease pathogenesis. We hypothesized that memory B
      cell pools from RRMS patients may specifically harbor a subset of potent neuro
      APC that support neuro-Ag reactive T-cell proliferation and cytokine secretion.
      To test this hypothesis, we compared CD80 and HLA-DR expression, IL-10 and
      lymphotoxin-alpha secretion, neuro-Ag binding capacity, and neuro-Ag presentation
      by memory B cells from RRMS patients to naive B cells from RRMS patients and to
      memory and naive B cells from healthy donors (HD). We identified memory B cells
      from some RRMS patients that elicited CD4(+) T-cell proliferation and IFN-gamma
      secretion in response to myelin basic protein and myelin oligodendrocyte
      glycoprotein. Notwithstanding the fact that the phenotypic parameters that
      promote efficient Ag presentation were observed to be similar between RRMS and HD
      memory B cells, a corresponding capability to elicit CD4(+) T-cell proliferation
      in response to myelin basic protein and myelin oligodendrocyte glycoprotein was
      not observed in HD memory B cells. Our results demonstrate for the first time
      that the memory B-cell pool in RRMS harbors neuro-Ag specific B cells that can
      activate T cells.

PMID- 20812239
TI  - Combined deficiency of MSH2 and SMU region abolishes class switch recombination.
AB  - Class switch recombination (CSR) is mediated by G-rich tandem repeated sequences
      termed switch regions. Transcription of switch regions generates single-stranded
      R loops that provide substrates for activation-induced cytidine deaminase. Mice
      deficient in MSH2 have a mild defect in CSR and analysis of their switch
      junctions has led to a model in which MSH2 is more critical for switch
      recombination events outside than within the tandem repeats. It is also known
      that deletion of the whole SMU region severely impairs but does not abrogate CSR
      despite the lack of detectable R loops. Here, we demonstrate that deficiency of
      both MSH2 and the SMU region completely abolishes CSR and that the abrogation
      occurs at the genomic level. This finding further supports the crucial role of
      MSH2 outside the tandem repeats. It also indicates that during CSR, MSH2 has
      access to activation-induced cytidine deaminase targets in R-loop-deficient IMU
      CMU sequences rarely used in CSR, suggesting an MSH2-dependent DNA processing
      activity at the IMU exon that may decrease with transcription elongation across
      the SMU region.

PMID- 20812241
TI  - Angiotensin-converting enzyme gene polymorphism and respiratory muscle function
      in infants.
AB  - OBJECTIVE: Angiotensin-converting enzyme (ACE) gene contains a polymorphism
      consisting of either the presence (I) or absence (D) of a 287-bp fragment. Recent
      studies have suggested that the I-allele may be associated with superior exercise
      endurance; respiratory muscle function may be similarly influenced. The pressure
      time index of inspiratory muscles (PTImus) is a measure of the load-capacity
      ratio of the inspiratory muscles. The objective of this study was to determine
      whether infants homozygous for the I-allele have lower PTImus compared to infants
      homozygous for the D-allele or heterozygous I/D. PATIENTS AND METHODS: One
      hundred thirty-two infants were studied. ACE genotyping was performed by
      polymerase chain reaction amplification, using DNA from peripheral blood. PTImus
      was calculated as (Pi(mean)/Pi(max)) * (T(i)/T(tot)), where Pi(mean) was the mean
      inspiratory pressure estimated from airway pressure, generated 100 ms after an
      occlusion (P(0.1)), Pi(max) was the maximum inspiratory pressure and T(i)/T(tot)
      was the ratio of the inspiratory time to the total respiratory cycle time.
      Pi(max) was the largest pressure generated during brief airway occlusions
      performed at the end of a spontaneous crying effort. RESULTS: Infants with I/I
      genotype had significantly lower PTImus than infants with either D/D or I/D
      genotypes (P = 0.000007). ACE genotype was significantly related (P = 0.005) to
      PTImus measurements, independent of other factors that may affect respiratory
      muscle function. CONCLUSION: These results suggest that an association of ACE
      genotypes with PTImus measurements may exist in infants.

PMID- 20812240
TI  - The effects of an intensive behavior and nutrition intervention compared to
      standard of care on weight outcomes in CF.
AB  - Inadequate intake and suboptimal growth are common problems for patients with CF
      and a critical target for intervention. The purpose of this study was to compare
      the growth outcomes of children with CF who participated in a randomized clinical
      trial to improve energy intake and weight to children with CF receiving standard
      of care during the same time period. Our primary outcome was change in body mass
      index z-score (BMI z-score) over 2 years. An exploratory outcome was forced
      expiratory volume at 1-sec (FEV(1) ) over 2 years. Participants were children
      ages 4-12 with CF, who participated in a randomized clinical trial of behavior
      plus nutrition intervention versus nutrition education alone, and a matched
      Comparison Sample receiving standard of care drawn from the Cystic Fibrosis
      Foundation (CFF) Registry. Children in the Clinical Trial Group (N=67)
      participated in a 9-week, nutrition intervention and were followed at regular
      intervals (3, 6, 12, 18, and 24 months) for 2 years post-treatment to obtain
      anthropometric and pulmonary function data. For each child in the Comparison
      Sample (N=346), these measures were obtained from the CFF Registry at matching
      intervals for the 27-month period corresponding to the clinical trial. Over 27
      months, children in the Clinical Trial Group (the combined sample of the behavior
      plus nutrition and the nutrition alone) demonstrated significantly less decline
      in BMI z-score, -0.05 (SD=0.68, CI= -0.23 to 0.13), as compared to children in
      the Comparison Sample, -0.21 (SD=0.67, CI= -0.31 to -0.11). No statistically
      significant differences were found for decline in FEV(1) between children in the
      Clinical Trial Group and the Comparison Sample. The key implication of these
      findings is that intensive behavioral and nutritional intervention is effective
      and needs to be adapted so that it can be broadly disseminated into clinical
      practice.

PMID- 20812242
TI  - Lung function in children with repaired tracheo-oesophageal fistula using the
      forced oscillation technique.
AB  - BACKGROUND: Tracheo-oesophageal fistula (TOF) and oesophageal atresia (OA) are
      congenital anomalies commonly associated with pulmonary complications during
      early childhood. This study investigated the role of the forced oscillation
      technique (FOT) in assessing lung function in young children with repaired
      TOF/OA. METHODS: Forty children with repaired TOF/OA of median (range) age 8.0
      (3.3-10.6) years, and 20 healthy children without TOF aged 6.1 (3.1-10.8) years
      were studied. FOT measurements were attempted in all subjects and spirometry only
      in those 6 years and above. Resistance and reactance (both hPasL(-1)) at 6 Hz
      (Rrs6 and Xrs6, respectively) and 8 Hz (Rrs8 and Xrs8) measured using FOT, and
      forced expired volume in 1 sec (FEV(1)), forced vital capacity, functional
      residual capacity, total lung capacity, and residual volume (all L) obtained from
      spirometry or plethysmography were compared with reference values and expressed
      as z-scores. RESULTS: Technically acceptable measurements of Rrs6, Rrs8, Xrs6,
      Xrs8, Fdep, and Fres were obtained in 37 children with TOF and 20 healthy
      children without TOF, respectively. Those with TOF had significantly higher mean
      (SD) z-scores for Rrs6 [0.99 (0.75)] versus healthy children without TOF [0.31
      (0.69)] and lower mean (SD) z-scores for Xrs6 [-1.04 (1.07)] versus healthy
      children without TOF [-0.34 (0.83)]. Spirometry was successful in 24 of the 29
      with TOF in whom it was attempted and all healthy children without TOF. Mean (SD)
      z-score for FEV(1) was significantly lower in those with TOF [-0.86 (1.13)]
      versus healthy children without TOF [0.67 (0.54)]. z-Scores for Rrs6 and FEV(1)
      were significantly correlated (r = -0.49; P = 0.003). CONCLUSIONS: Children with
      repaired TOF have diminished lung function compared with healthy children. FOT is
      sensitive and correlates well with standard spirometry. It can be used to measure
      lung function in younger children when spirometry is difficult to perform and
      should be considered as an objective method for monitoring clinical progress in
      young children with TOF.

PMID- 20812243
TI  - Predictors of insufficient sweat production during confirmatory testing for
      cystic fibrosis.
AB  - Michigan's Newborn Screening (NBS) Program began statewide screening for cystic
      fibrosis (CF) in October 2007. Confirmatory sweat testing is performed in infants
      having initial immunoreactive trypsinogen concentrations >= 99.8th percentile or
      >= 96 th percentile and at least one CF mutation identified by DNA analysis. Some
      infants fail to produce a sufficient quantity of sweat (QNS-quantity not
      sufficient) to test for CF, meaning disease confirmation is delayed and sweat
      testing is later repeated. In this study, we evaluate predictors of QNS results.
      Information from the linked birth certificates and NBS diagnostic confirmation
      data were used. The study population was resident infants born in Michigan in
      2008 who underwent a sweat test. Bivariate analyses revealed that preterm birth,
      low birth weight, CF care center, and race were significantly associated with QNS
      sweat testing results. Adjusted analyses indicated that preterm infants were 2.4
      times more likely to have QNS results (95% CI 0.9, 6.4). When age at time of
      test, accounting for gestational age (gestational age at delivery plus
      postdelivery age of life=corrected age), was used in the multivariable model,
      infants <39 weeks were 7.4 times more likely to have QNS results (95% CI 2.5,
      21.8). Waiting to sweat test until an infant is aged 39 weeks or more (corrected
      age) would likely reduce the rate of QNS results, thereby reducing the burden of
      repeat sweat testing on families and healthcare providers. Further research is
      necessary to understand the impact of potential delays in diagnosis/treatment
      relative to postponing sweat testing.

PMID- 20812244
TI  - Is static hyperinflation a limiting factor during exercise in adolescents with
      cystic fibrosis?
AB  - Increased work of breathing is considered to be a limiting factor in patients
      with cystic fibrosis (CF) performing aerobic exercise. We hypothesized that
      adolescents with CF and with static hyperinflation are more prone to a
      ventilatorily limited exercise capacity than non-static hyperinflated adolescents
      with CF. Exercise data of 119 adolescents with CF [range 12-18 years], stratified
      for static hyperinflation, defined as ratio of residual volume to total lung
      capacity (RV/TLC) > 30%, were obtained during a progressive bicycle ergometer
      test with gas analysis and analyzed for ventilatory limitation. Static
      hyperinflation showed a significant, though weak association (Phi 0.38; P <
      0.001) with a ventilatorily limited exercise capacity (breathing reserve index at
      maximal effort >0.70; FEV(1)  < 80% predicted and reduced exercise capacity,
      defined as VO(2peak)  < 85% predicted). Analysis of association for increasing
      degrees of hyperinflation showed an increase to Phi 0.49 (P < 0.001) for RV/TLC >
      50%. In adolescents with static hyperinflation, peak work rate (W(peak) ; 3.1 +/-
      0.7 W/kg (75.1 +/- 17.3% of predicted), peak oxygen uptake (VO(2peak) /kg
      (ml/min/kg); 39.2 +/- 9.2 ml/min/kg (91.0 +/- 20.3% of predicted), peak heart
      rate (HR(peak) ; 176 +/- 19 beats/min) were significantly (P < 0.05) decreased
      when compared with non-static hyperinflated adolescents (W(peak) 3.5 +/- 0.5 W/kg
      (81.4 +/- 10.0% of predicted)); VO(2peak) /kg (ml/min/kg); 43.1 +/- 7.5 ml/min/kg
      (98.0 +/- 15.1% of predicted); and HR(peak) 185 +/- 14 beats/min). Additionally,
      no difference was found in the degree of association of FEV(1) (%) and RV/TLC (%)
      with VO(2peak) /kg(pred) and W(peak) /kg(Pred) , but we found the RV/TLC (%) to
      be a slightly stronger predictor of VO(2peak) /kg(pred) and W(peak) /kg(Pred)
      than FEV(1) (%). These results indicate that the presence of static
      hyperinflation in adolescents with CF by itself does not strongly influence
      ventilatory constraints during exercise and that static hyperinflation is only a
      slightly stronger predictor of W(peak) /kg(Pred) and VO(2peak) /kg(Pred) than
      airflow obstruction (FEV(1) (%)).

PMID- 20812246
TI  - Parental perspectives on influenza vaccination in children with asthma.
AB  - BACKGROUND: Influenza is an important cause of epidemic and pandemic disease
      leading to mortality and morbidity in children. Despite great efforts to increase
      influenza vaccination, many children with chronic medical conditions do not
      receive influenza vaccine. Our aim was to identify the demographic factors and
      asthma-associated characteristics related to vaccination, caregivers' attitudes
      and knowledge about influenza disease during the 2007-2008 influenza season.
      METHODS: Caregivers of children with asthma were surveyed via a self-administered
      questionnaire to document their knowledge about influenza disease and vaccine and
      factors influencing vaccination. RESULTS: We enrolled 311 children with asthma.
      The rate of lifetime influenza vaccination was 69.5%, whereas 51.8% of the
      patients had been vaccinated in the current season. There were no significant
      differences in demographic factors and asthma control parameters between the
      groups who received or did not receive influenza vaccine. Most of the parents
      whose children were vaccinated believed that influenza vaccination would decrease
      the prevalence and severity of asthma attacks (P < 0.05). The most important
      reason cited by parents for deciding on the influenza vaccine for their child was
      physician recommendation (80.1%). The major reasons for declining the vaccination
      were unawareness that the influenza vaccine was a requirement for their child
      (29.3%) and illness at the time of vaccination (20%). CONCLUSION: Physician
      recommendation is important in the influenza vaccination decision. Demographic
      factors and asthma control parameters had no influence on immunization uptake but
      parental beliefs and attitudes could be determinant. Greater effort is needed to
      increase influenza vaccination rates, in children with asthma.

PMID- 20812245
TI  - Pediatric OSA: a case for "United We Stand" in the way of a breath.

PMID- 20812248
TI  - MRT letter: A novel tegumental gland in female imagoes of the neotropical termite
      Cornitermes cumulans (Isoptera, termitidae, syntermitinae).
AB  - In general, the exocrine glands of social insects are structures involved in the
      chemical communication associated with social life. Here, we report the discovery
      of an unknown tegumental gland that is present in the female imagoes of
      Cornitermes cumulans and occurs next to the well-developed tergal glands that
      have previously been described. The tegumental glands release their secretion in
      the intersegmental membrane and are composed of bicellular units, a secretory
      cell and a canal cell, that are closely located to the epidermal cells in the
      inferior part of the eighth and ninth tergites. The ultrastructure of the
      glandular cells showed abundant smooth endoplasmic reticulum, suggesting that the
      secretion may be pheromonal, although its function is still unknown. These
      exocrine structures are facing the tergal glands, and we hypothesized that they
      act synergistically with the tergal glands to generate short-range attraction
      during tandem behavior.

PMID- 20812247
TI  - Safety in treatment of ventilator-associated pneumonia due to extensive drug
      resistant Acinetobacter baumannii with aerosolized colistin in neonates: a
      preliminary report.
AB  - BACKGROUND: Infections caused by extensive drug-resistant Acinetobacter baumannii
      (XDR-AB) have been increasingly observed and are associated with a high mortality
      rate. We present our experience using aerosolized colistin for the treatment of
      ventilator-associated pneumonia (VAP) due to XDR-AB in neonates. METHODS: The
      clinical data of neonates who received aerosolized 4 mg per kg of colistin base
      twice daily as an adjunctive therapy for VAP caused by XDR-AB between July 2008
      and September 2009 were retrospectively reviewed. The outcomes were compared with
      the neonates with VAP from XDR-AB in October 2006-September 2007 who did not
      receive aerosolized colistin. RESULTS: During the study period, eight neonates
      (three preterm and five term neonates) with VAP caused by XDR-AB received
      aerosolized colistin. All isolated pathogens from the tracheobronchial specimens
      of the eight patients were XDR-AB susceptible to colistin only. Six patients
      received aerosolized colistin without concomitant intravenous colistin. All
      children were cured with eradication of XDR-AB from respiratory secretions. Seven
      patients survived and were discharged from the hospital, and one died from
      bacterial sepsis unrelated to the VAP episode. There were no clinical or
      laboratory adverse events related to aerosolized colistin. Compared to the seven
      neonates in the earlier period, the neonates who received aerosolized colistin
      had higher birth weight and gestational age, and lower mortality rate (13% vs.
      71%, P=0.04). CONCLUSIONS: Aerosolized colistin may be a useful adjunctive
      therapy in VAP due to XDR-AB. The use of aerosolized colistin in neonates should
      be investigated in a larger controlled study.

PMID- 20812249
TI  - A novel consistent photomicrography technique using a reference slide made of
      neutral density filter.
AB  - Obtaining consistent photomicrographic images of pathology slides is not always
      easy because of many different types and settings of the equipment such as the
      microscopes and digital cameras. In this study, we developed a photomicrography
      technique that could acquire consistent images of pathology slides. The neutral
      density (ND) filter was attached to a transparent glass slide as a reference
      slide, photographed using consistent settings, and acquired images that harbored
      all of the areas of gray, white, and black. In the same way, the slide was
      replaced by the actual pathology slide, and photomicrographed. To simulate
      different light environment, the above photographic session was repeated using
      two different light intensities and microscopes. A graphic program was used to
      adjust levels of the reference slide images and this leveling, or calibration,
      was saved as a file for each. This file for leveling process was applied to
      actual subsequent photomicrographic images. The same sites of noncalibrated and
      calibrated images of the pathology slide were calculated into CIELAB or CIE
      L*a*b* coordinates. Then, the color differences (DeltaE*ab) were calculated. As
      results, in the study using a 50% transmittance ND filter, two original different
      images were made nearly identical to the unaided eye, especially in two-point
      (white and gray) and three-point (black, white, and gray) leveling. In comparison
      of different light intensities, the DeltaE*ab of the selected area was 0.9 in two
      point leveling. Between different microscopes, 10.7 of DeltaE*ab was the smallest
      value in three-point leveling. This method would be helpful for acquiring
      consistent photomicrographic images of pathology slides.

PMID- 20812250
TI  - Antennal sensilla of the pine weevil Pissodes nitidus Roel. (Coleoptera:
      Curculionidae).
AB  - The antennal sensilla of the pine weevil (Pissodes nitidus Roel.) were observed
      with scanning electron microscopy and transmission electron microscopy (TEM). The
      weevil antenna consists of a long scape, a pedicel, and a flagellum with 10
      segments; the last four flagellum segments are fused, forming the antennal club,
      which is densely covered by various sensilla. In both sexes, six types of
      sensilla, sensilla palmate 1-4, sensilla chaetica, sensilla trichoid, sensilla
      basiconic 1-2, sensilla rod-like 1-3, sensilla falciform, were identified.
      Sensilla palmate represent a unique sensillum type in the Pissodes genus, and
      named here after their palmate shape, also represent the most abundant sensillum
      type. The TEM analysis of sensilla palmate represents the first such analysis of
      this sensillum type, and we speculate that the sensilla have an olfactory
      function. The sensilla trichoid and chaetica were evenly distributed on the three
      or four hair bands of the club, with much lower numbers than the palmate
      sensilla. No significant sexual differences in the types, numbers, and
      distribution of the antennal sensilla were found except for the size. TEM
      observation indicated that sensilla chaetica and trichoid may function as
      olfactory sensors. The putative functions of other sensilla type were also
      discussed with reference to their morphology, distribution, and ultrastructure.

PMID- 20812251
TI  - Idiopathic acute eosinophilic pneumonia requiring ECMO in a teenager smoking
      tobacco and cannabis.
AB  - We describe what we believe is an entirely novel case of a 15-year-old boy with
      idiopathic acute eosinophilic pneumonia and unusual, resistant hypoxemia which
      necessitated extracorporeal membrane oxygenation. Response to corticosteroids was
      excellent and a full recovery was observed. Smoking cigarettes and cannabis on
      the day the symptoms began may have contributed to the occurrence of this rare
      disease.

PMID- 20812252
TI  - Airway hyperresponsiveness is associated with total serum immunoglobulin E and
      sensitization to aeroallergens in Korean adolescents.
AB  - BACKGROUND: Allergen sensitization and airway hyperresponsiveness (AHR) are the
      most important characteristics of bronchial asthma and their correlation has been
      speculated. OBJECTIVE: We attempted to investigate the relationship between
      sensitization to allergens and AHR to methacholine in Korean high school
      students. METHODS: A questionnaire survey, methacholine bronchial provocation
      tests, and skin-prick tests for 16 major allergens were performed on 724
      students. The mean age of participants was 15.79 +/- 0.40 years old. Serum total
      immunoglobulin E (IgE) and the fraction of blood eosinophils were measured.
      RESULTS: AHR (PC(20) < 16 mg/ml) was present in 12.3%. Log total IgE was higher
      in AHR-positive group than negative group (4.22 +/- 1.55, 3.70 +/- 1.33, P =
      0.001). Three hundred eighty-four students (53.0%) were sensitized to more than
      one allergen, and among them Dermatophagoides pteronyssinus (Der p, 295 students,
      40.7%) and Dermatophagoides farinae (Der f, 301 students, 41.6%) were most
      common. The risk of AHR development was high in the group who had sensitization
      to one allergen (adjusted odds ratio [aOR] = 1.97, 95% confidence interval [CI]:
      1.13-3.44, P = 0.018) and to more than two allergens (aOR = 2.94, 95% CI: 1.32
      6.57, P = 0.009). Among the specific allergens, AHR was developed in those who
      were sensitized to Der f (aOR = 1.73, 95% CI: 1.04-2.86, P = 0.033), dog dander
      (aOR = 3.97, 95% CI: 1.67-9.51, P = 0.002), and Alternaria (aOR = 3.19, 95% CI:
      1.24-6.41, P = 0.016). In the groups with high IgE (>300 IU/ml) and high
      eosinophil fraction (>4%), AHR was more developed than groups who were low in
      each (aOR = 2.73, 95% CI: 1.15-6.51, P = 0.023; aOR = 10.82, 95% CI: 3.33-35.08,
      P = 0.001). CONCLUSION: The risk of AHR development was closely linked with
      allergen sensitization itself, and the number or types of sensitized allergens
      such as indoor and fungal allergens in Korean young adolescents.

PMID- 20812253
TI  - Thioredoxin protects fetal type II epithelial cells from hyperoxia-induced
      injury.
AB  - Oxygen toxicity is known to be one of the major contributors to bronchopulmonary
      dysplasia, a chronic lung disease in premature infants. Thioredoxin (Trx) is an
      antioxidant that prevents oxidative stress-induced cell death, suggesting a
      potential therapeutic role in bronchopulmonary dysplasia. The aim of this study
      was to determine the role of Trx in the pathogenesis of hyperoxia-induced
      alveolar epithelial cell injury. Alveolar type II epithelial cells from fetal rat
      lung were exposed to hyperoxia in vitro in the presence or absence of recombinant
      human Trx (rhTrx 2 ug/ml). Cell viability was assessed by 3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyl tetrazolium bromide assay. Apoptosis and levels of reactive
      oxygen species (ROS) were measured by flow cytometry. Activation of mitogen
      activated protein kinase (MAPK) and phosphatidylinositol 3-kinase-Akt (PI3K-Akt)
      pathways were detected by Western blotting. We also investigated the effects of
      rhTrx on the following antioxidants (superoxide dismutase, catalase, and
      glutathione peroxidase). Trx significantly reduced hyperoxia-induced cell death
      and increased cell viability. In addition, ROS generation in type II cells was
      inhibited by rhTrx under hyperoxic conditions. We demonstrated that rhTrx
      protected type II cells against hyperoxic injury via sustaining the extracellular
      signal regulated kinase and PI3K activation, and decreasing of c-Jun N-terminal
      protein kinase and p38 activation. The results also showed manganese superoxide
      dismutase and glutathione peroxidase activities were increased by rhTrx in type
      II cells exposed to hyperoxia.Taken together, these results demonstrate that
      rhTrx administration markedly attenuates hyperoxia-induced type II cell injury
      through reduction of ROS generation, elevation of antioxidant activities and
      regulation of both MAPK and PI3K-Akt signaling pathways.

PMID- 20812254
TI  - Micropatterning and characterization of electrospun poly(epsilon
      caprolactone)/gelatin nanofiber tissue scaffolds by femtosecond laser ablation
      for tissue engineering applications.
AB  - Experimental investigations aimed at assessing the effectiveness of femtosecond
      (FS) laser ablation for creating microscale features on electrospun poly(epsilon
      caprolactone) (PCL)/gelatin nanofiber tissue scaffold capable of controlling cell
      distribution are described. Statistical comparisons of the fiber diameter and
      surface porosity on laser-machined and as-spun surface were made and results
      showed that laser ablation did not change the fiber surface morphology. The
      minimum feature size that could be created on electrospun nanofiber surfaces by
      direct-write ablation was measured over a range of laser pulse energies. The
      minimum feature size that could be created was limited only by the pore size of
      the scaffold surface. The chemical states of PCL/gelatin nanofiber surfaces were
      measured before and after FS laser machining by attenuated total reflectance
      Fourier transform infrared (ATR-FTIR) spectroscopy and X-ray photoelectron
      spectroscopy (XPS) and showed that laser machining produced no changes in the
      chemistry of the surface. In vitro, mouse embryonic stem cells (mES cells) were
      cultured on as-spun surfaces and in laser-machined microwells. Cell densities
      were found to be statistically indistinguishable after 1 and 2 days of growth.
      Additionally, confocal microscope imaging confirmed that spreading of mES cells
      cultured within laser-machined microwells was constrained by the cavity walls,
      the expected and desired function of these cavities. The geometric constraint
      caused statistically significant smaller density of cells in microwells after 3
      days of growth. It was concluded that FS laser ablation is an effective process
      for microscale structuring of these electrospun nanofiber tissue scaffold
      surfaces.

PMID- 20812255
TI  - Quantitative influence of endogenous salicylic acid level on taxuyunnanine C
      biosynthesis in suspension cultures of Taxus chinensis.
AB  - Intracellular signals are critical to secondary metabolite biosynthesis by plant
      cells, but their quantitative effects are not yet well understood in plant cell
      cultures. Using Taxus chinensis suspension culture, which has the potential to
      provide a sustainable supply of highly useful bioactive taxoids, this work
      investigated the impact of endogenous salicylic acid (SA) level on taxuyunnanine
      C (Tc) biosynthesis. It was observed that the Tc accumulation was strongly
      dependent on the endogenous SA level. Under elicitation with an endogenous SA of
      97.1 +/- 11.8 ug/g dry weight, a maximal Tc content of 10.3 +/- 0.52 mg/g dry
      weight was obtained. The transcription levels of Tc biosynthetic genes of
      geranylgeranyl diphosphate synthase and taxadiene synthase were also analyzed,
      and they were increased with increase of internal SA level. The results
      demonstrated that manipulation of endogenous SA level could be an efficient
      strategy for improving secondary metabolite biosynthesis in plant cell culture.

PMID- 20812257
TI  - Bacillus subtilis pgsE (Formerly ywtC) stimulates poly-gamma-glutamate production
      in the presence of zinc.
AB  - Poly-gamma-glutamate (PGA) is a versatile nylon-like material, and enhanced
      production of PGA is required for various bio-industrial applications. In this
      study, we first examined the effects of available sugars on the production of
      Bacillus subtilis PGA, and demonstrated the good applicability of pentoses (e.g.,
      D-xylose). Then, we characterized the pgsE gene of B. subtilis, which encodes a
      6.5-kDa protein of 55 amino acids (PgsE), as a genetic tool for increasing the
      yield of PGA without changing its structural features (e.g., polymer
      stereochemistry and molecular size distribution). In the presence of Zn(2+), the
      induction of PgsE tripled the PGA productivity of B. subtilis subsp.
      chungkookjang. This finding will contribute to the establishment of an improved
      PGA-production system.

PMID- 20812256
TI  - Cellular arrays for large-scale analysis of transcription factor activity.
AB  - Identifying molecular mechanisms or therapeutic targets is typically based on
      large-scale cellular analysis that measures the abundance of mRNA or protein;
      however, abundance does not necessarily correlate with activity. We report a
      method for direct large-scale quantification of active pathways that employs a
      cellular array with parallel gene delivery of constructs that report pathway
      activity. The reporter constructs encode luciferase, whose expression is
      influenced by binding of transcription factors (TFs), which are the downstream
      targets of signaling pathways. Luciferase levels are quantified by
      bioluminescence imaging (BLI), which allows for rapid, non-invasive measurements.
      Activity profiles by BLI of 32 TFs were robust, consistent, and reproducible, and
      correlated with standard cell lysis techniques. The array identified five TFs
      with differential activity during phorbol-12-myristate-13-acetate (PMA)-induced
      differentiation of breast cancer cells. A system for rapid, large-scale, BLI
      quantification of pathway activity provides an enabling technology for
      mechanistic studies of cellular responses and processes.

PMID- 20812258
TI  - Modulation of viability of live cells by focused ion-beam exposure.
AB  - Introduction of membrane-impermeant substances into living cells is the key
      method to understand contemporary cellular processes by investigating cellular
      responses and phenotypes. Here, we performed gold ion beam exposure into live
      cells by using the focused ion beam implantation method, which was originally
      developed to precisely control semiconductor device performances. We evaluated
      the viability of the gold-irradiated cells by measuring the concentration of
      adenosine triphosphate (ATP), which is an intracellular energy source produced in
      the mitochondrial membrane. The viability of the irradiated cells was found to be
      20% higher than that of the unirradiated control cells. The atoms might promote
      the energy generating processes within the mitochondrion. Our results suggest
      that the viability of living cells can be modulated by accurately controlling the
      dopant atom numbers. Our technique may be considered as a potential tool in life
      and medical sciences to quantitatively elucidate the dose-dependent effects of
      dopants.

PMID- 20812259
TI  - Metabolic engineering of Escherichia coli for the production of cadaverine: a
      five carbon diamine.
AB  - A five carbon linear chain diamine, cadaverine (1,5-diaminopentane), is an
      important platform chemical having many applications in chemical industry. Bio
      based production of cadaverine from renewable feedstock is a promising and
      sustainable alternative to the petroleum-based chemical synthesis. Here, we
      report development of a metabolically engineered strain of Escherichia coli that
      overproduces cadaverine in glucose mineral salts medium. First, cadaverine
      degradation and utilization pathways were inactivated. Next, L-lysine
      decarboxylase, which converts L-lysine directly to cadaverine, was amplified by
      plasmid-based overexpression of the cadA gene under the strong tac promoter.
      Furthermore, the L-lysine biosynthetic pool was increased by the overexpression
      of the dapA gene encoding dihydrodipicolinate synthase through the replacement of
      the native promoter with the strong trc promoter in the genome. The final
      engineered strain was able to produce 9.61 g L(-1) of cadaverine with a
      productivity of 0.32 g L(-1) h(-1) by fed-batch cultivation. The strategy
      reported here should be useful for the bio-based production of cadaverine from
      renewable resources.

PMID- 20812260
TI  - Increasing cellulose accessibility is more important than removing lignin: a
      comparison of cellulose solvent-based lignocellulose fractionation and soaking in
      aqueous ammonia.
AB  - While many pretreatments attempt to improve the enzymatic digestibility of
      biomass by removing lignin, this study shows that improving the surface area
      accessible to cellulase is a more important factor for achieving a high sugar
      yield. Here we compared the pretreatment of switchgrass by two methods, cellulose
      solvent- and organic solvent-based lignocellulose fractionation (COSLIF) and
      soaking in aqueous ammonia (SAA). Following pretreatment, enzymatic hydrolysis
      was conducted at two cellulase loadings, 15 filter paper units (FPU)/g glucan and
      3 FPU/g glucan, with and without BSA blocking of lignin absorption sites. The
      hydrolysis results showed that the lignin remaining after SAA had a significant
      negative effect on cellulase performance, despite the high level of
      delignification achieved with this pretreatment. No negative effect due to lignin
      was detected for COSLIF-treated substrate. SEM micrographs, XRD crystallinity
      measurements, and cellulose accessibility to cellulase (CAC) determinations
      confirmed that COSLIF fully disrupted the cell wall structure, resulting in a 16
      fold increase in CAC, while SAA caused a 1.4-fold CAC increase. A surface plot
      relating the lignin removal, CAC, and digestibility of numerous samples (both
      pure cellulosic substrates and lignocellulosic materials pretreated by several
      methods) was also developed to better understand the relative impacts of
      delignification and CAC on glucan digestibility.

PMID- 20812261
TI  - Perfusion of 3D encapsulated hepatocytes--a synergistic effect enhancing long
      term functionality in bioreactors.
AB  - Long-term primary cultures of hepatocytes are essential for bioartificial liver
      (BAL) devices and to reduce and replace animal tests in lead candidate
      optimization in drug discovery and toxicology tests. The aim of this work was to
      improve bioreactor cultures of hepatocyte spheroids by adding a more
      physiological perfusion feeding regime to these bioreactor systems. A continuous
      perfusion feeding was compared with 50% medium replacement (routinely used for in
      vitro tests) at the same dilution rate, 0.125 day(-1), for three operative weeks.
      Perfusion feeding led to a 10-fold improvement in albumin synthesis in
      bioreactors containing non-encapsulated hepatocyte spheroids; no significant
      improvement was observed in phase I drug metabolizing activity. When ultra high
      viscous alginate encapsulated spheroids were cultured in perfusion, urea
      synthesis, phase I drug metabolizing activity and oxygen consumption had a
      threefold improvement over the 50% medium replacement regime; albumin production
      was the same for both feeding regimes. The effective diffusion of albumin in the
      alginate capsules was 7.75.10(-9) cm(2) s(-1) and no diffusion limitation for
      this protein was observed using these alginate capsules under our operational
      conditions. In conclusion, perfusion feeding coupled with alginate encapsulation
      of hepatocyte spheroids showed a synergistic effect with a threefold improvement
      in three independent liver-specific functions of long-term hepatocyte spheroid
      cultures.

PMID- 20812262
TI  - A systematic review of diagnostic procedures to detect midgut neuroendocrine
      tumors.
AB  - The aim of this work was to assess the diagnostic yield of some clinical
      diagnostic procedures utilized to establish a diagnosis of midgut neuroendocrine
      tumors (NETs). Medical databases published between 1982 and 2007 were analyzed.
      Seventeen observational studies, including 629 patients, met the inclusion
      criteria. Urinary 5-HIAA is the first test to prescribe in patients with flushing
      or persistent, unexplained diarrhea. Abdominal CT scan and OctreoScan should be
      prescribed whenever NET is suspected.

PMID- 20812263
TI  - Preliminary experience with bladder preservation for lower rectal cancers
      involving the lower urinary tract.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the feasibility
      of en bloc colorectal resection combined with radical prostatectomy as an
      alternative to total pelvic exenteration (TPE) for patients with locally advanced
      rectal cancer involving the lower urinary tract organs. METHODS: Twenty men with
      primary rectal cancer clinically involving the lower urinary tract organs
      underwent extended colorectal resection combined with radical prostatectomy. Data
      were entered prospectively into a database. Oncological and functional outcomes
      were analyzed. RESULTS: Anal sphincter-preserving operation (SPO) with radical
      prostatectomy was performed in 12 patients, abdominoperineal resection with
      radical prostatectomy in 8, and urinary reconstruction in 16. Morbidity and
      mortality rates were 35.0% and 0%, respectively. Five-year overall and disease
      free survival rates were 83.6% and 42%, respectively. The cumulative 5-year local
      recurrence rate was 20.0%. All patients with urinary reconstruction achieved good
      voiding function, and patients with SPO showed acceptable anal function.
      CONCLUSIONS: For lower rectal cancers involving lower urinary tract, en bloc
      rectal resection combined with radical prostatectomy appears oncologically
      acceptable and can reduce the number of TPEs.

PMID- 20812264
TI  - The effects of bevacizumab on postoperative complications in patients undergoing
      colorectal and pancreatic cancer resection.
AB  - Bevacizumab (AvastinTM; rhuMab VEGF), a monoclonal antibody targeting vascular
      endothelial growth factor (VEGF), has seen increased use in the perioperative
      treatment of colorectal and pancreatic cancer. Little is known, however,
      regarding its impact on surgical outcomes in patients undergoing resection. The
      objective of this review was to examine if the addition of bevacizumab to
      existing neoadjuvant regimens increases morbidity after cancer resection.

PMID- 20812265
TI  - An experimental and computational study on the epimeric contribution to the
      infrared spectrum of budesonide.
AB  - Budesonide is a mixture of 22R and 22S epimers. The epimeric content of
      budesonide was reported in both British and European pharmacopoeias to be within
      the range of 60-49/40-51 for R and S epimers, respectively. In this work,
      contribution of the two epimers to the overall infrared spectrum of budesonide
      has been investigated by quantum chemical calculations.

PMID- 20812266
TI  - Robotic single-incision transabdominal and transvaginal surgery: initial
      experience with intersecting robotic arms.
AB  - BACKGROUND: Single-incision laparoscopic and natural orifice translumenal
      endoscopic surgery (NOTES) are technically challenging methods. Robotics might
      have the potential to overcome such hurdles with computer technology. METHODS:
      The da Vinci Standard and S System (Intuitive, Sunnyvale, USA) were used in human
      cadavers and pigs to perform single-incision transabdominal and transvaginal
      surgery. Robotic arms were crossed and control-switched to achieve intuitive
      control. RESULTS: It was possible to perform robotic single-incision laparoscopy
      in the typical, intuitive fashion. Transvaginal set-up, including docking of the
      system and introduction of instruments into the abdominal cavity, was possible
      but no useful manipulation could be performed. CONCLUSIONS: While robotic NOTES
      with the da Vinci surgical system was not successful, robotic single-incision
      surgery is feasible using the above set-up. This new approach seems to offer the
      advantages of single-incision surgery while maintaining the intuitive control of
      robotic surgery. Clinical application appears justified.

PMID- 20812267
TI  - Motorization of a surgical microscope for intra-operative navigation and
      intuitive control.
AB  - BACKGROUND: During surgical procedures, various medical systems, e.g. microscope
      or C-arm, are used. Their precise and repeatable manual positioning can be very
      cumbersome and interrupts the surgeon's work flow. Robotized systems can assist
      the surgeon but they require suitable kinematics and control. However,
      positioning must be fast, flexible and intuitive. METHODS: We describe a fully
      motorized surgical microscope. Hardware components as well as implemented
      applications are specified. The kinematic equations are described and a novel
      control concept is proposed. RESULTS: Our microscope combines fast manual
      handling with accurate, automatic positioning. Intuitive control is provided by a
      small remote control mounted to one of the surgical instruments. Positioning
      accuracy and repeatability are < 1 mm and vibrations caused by automatic
      movements fade away in about 1 s. CONCLUSION: The robotic system assists the
      surgeon, so that he can position the microscope precisely and repeatedly without
      interrupting the clinical workflow. The combination of manual und automatic
      control guarantees fast and flexible positioning during surgical procedures.

PMID- 20812269
TI  - Kinematics of a robotic 3UPS1S spherical wrist designed for laparoscopic
      applications.
AB  - BACKGROUND: Current robotic orientation surgical devices used to be large, in
      order to cover the needed workspace and to be rigid enough to resist the forces
      that occur during surgery. The disadvantages of the large size of the devices are
      the ergonomics, collisions and interference with the surgeons. This paper
      presents the first steps that have been carried out on the development of a small
      spherical wrist for laparoscopic applications. METHODS: Screw theory for
      kinematic analysis and the design of parallel robots have been used for choosing
      the kinematic architecture of the first prototype of the laparoscopic wrist. The
      kinematic equations of the platform are described and the Jacobian matrix
      calculated. RESULTS: The kinematics of this device is a 3UPS-1S parallel
      architecture. The work presented here shows the concept of the device, its
      design, that it was made under intrinsic safety criteria, its kinematic analysis
      and the first results and images of the built prototype. The kinematic analysis
      is made using screw theory and it is used to verify the optimization of the
      design. CONCLUSIONS: A new design for a smart and small spherical wrist is
      developed. Ergonomics for the surgical team is a design criterion that should be
      introduced to the design process for an operating-room robotic tool. Parallel
      robots architecture can contribute to new devices that fit this criterion.

PMID- 20812268
TI  - Automatic determination of optimal linear drilling trajectories for cochlear
      access accounting for drill-positioning error.
AB  - BACKGROUND: Cochlear implantation is a surgical procedure in which an electrode
      array is permanently implanted into the cochlea to stimulate the auditory nerve
      and allow deaf people to hear. Percutaneous cochlear access, a new minimally
      invasive implantation approach, requires drilling a single linear channel from
      the skull surface to the cochlea. The focus of this paper addresses a major
      challenge with this approach, which is the ability to determine, in a pre
      operative CT, a safe and effective drilling trajectory. METHODS: A measure of the
      safety and effectiveness of a given trajectory relative to sensitive structures
      is derived using a Monte Carlo approach. The drilling trajectory that maximizes
      this measure is found using an optimization algorithm. RESULTS: In tests on 13
      ears, the technique was shown to find approximately twice as many acceptable
      trajectories as those found manually by an experienced surgeon. CONCLUSIONS:
      Using this method, safe trajectories can be automatically determined quickly and
      consistently.

PMID- 20812270
TI  - Robotic hip arthroscopy in human anatomy.
AB  - BACKGROUND: Robotic technology offers technical advantages that might offer new
      solutions for hip arthroscopy. METHODS: Two hip arthroscopies were performed in
      human cadavers using the da Vinci surgical system. During both surgeries, a
      robotic camera and 5 or 8 mm da Vinci trocars with instruments were inserted into
      the hip joint for manipulation. RESULTS: Introduction of cameras and working
      instruments, docking of the robotic system and instrument manipulation was
      successful in both cases. The long articulating area of 5 mm instruments limited
      movements inside the joint; an 8 mm instrument with a shorter area of
      articulation offered an improved range of motion. CONCLUSIONS: Hip arthroscopy
      using the da Vinci standard system appears a feasible alternative to standard
      arthroscopy. Instruments and method of application must be modified and improved
      before routine clinical application but further research in this area seems
      justified, considering the clinical value of such an approach.

PMID- 20812271
TI  - Concurrent robotic trans-abdominal pre-peritoneal (TAP) herniorrhaphy during
      robotic-assisted radical prostatectomy.
AB  - BACKGROUND: Robotic prostatectomy (RP) is now increasingly performed because it
      allows for precise dissection of neurovascular structures with better outcomes.
      It is estimated that 5-12% of candidates for radical prostatectomy have
      detectable inguinal hernias, and simultaneous mesh hernioplasty is now well
      supported. A disadvantage of radical prostatectomy is obliteration of the
      preperitoneal space of Bogros, which can make future totally extraperitoneal
      (TEP) herniorrhaphy difficult and prone to complication. METHODS: Four patients
      underwent RP using the DaVinci system. Six clinically detectable inguinal hernias
      were repaired. Upon completion of the prostatectomy, the peritoneum overlying the
      myopectineal orifice of Fruchaud was opened, the orifice was dissected free and
      the hernia reduced. A 3 x 6 inch polypropylene mesh or 4 x 6 inch polyester mesh
      was then affixed overlying the orifice with titanium tacks, and the peritoneum
      was closed over the mesh using a running absorbable suture. RESULTS: The mean
      operating time for the TAP was 24 min. There were no postoperative complications.
      At a mean follow-up of 34 months, no recurrence was noted. CONCLUSIONS: With the
      increasing incidence of RP, we advocate the concurrent repair of any detectable
      inguinal hernias at the time of prostatectomy. The preperitoneal placement of a
      polypropylene or polyester mesh secured with a tacking device and a peritoneal
      closure performed with a running absorbable suture is uniquely suited to the
      abilities of the robot, and provides a durable repair.

PMID- 20812272
TI  - Accuracy and speed trade-off in robot-assisted surgery.
AB  - BACKGROUND: Controlling surgical task speed and maintaining accuracy are vital
      components of robotic surgical skills. This study was designed to investigate the
      relationship between accuracy and speed for robot-assisted surgical skills.
      METHODS: Ten participants were asked to alternately touch two circular targets
      with various dimensions and distances between two targets, using the da Vinci
      Surgical System. The design of this study was based on Fitt's law. Statistical
      correlations between the index of difficulty (ID) and the movement time (MT), as
      well as the ID and the smoothness of the movement, were analysed. RESULTS: A
      significant linear correlation between MT and ID was shown. Speed was reduced to
      maintain accuracy as the level of task difficulty increased. There was no
      significant correlation between the smoothness of the movement and ID.
      CONCLUSIONS: The trade-off between speed and accuracy plays an important role in
      robot-assisted surgical proficiency.

PMID- 20812276
TI  - Use of Yokukansan (TJ-54) in the treatment of neurological disorders: a review.
AB  - Kampo herbal remedies are reported to have a wide range of indications and have
      attracted attention due to reports suggesting that these remedies are effective
      when used in disease treatment while maintaining a favourable quality of life.
      Yokukansan, also known as TJ-54, is composed of seven herbs; Angelica acutiloba,
      Atractylodes lancea, Bupleurum falcatum, Poria cocos, Glycyrrhiza uralensis,
      Cnidium officinale and Uncaria rhynchophylla. Yokukansan is used to treat
      insomnia and irritability as well as screaming attacks, sleep tremors and hypnic
      myoclonia, and neurological disorders which include dementia and Alzheimer's
      disease - the focus of this article. It is concluded that Yokukansan is a
      versatile herbal remedy with a variety of effects on various neurological states,
      without reported adverse effects. Traditional herbal medicines consist of a
      combination of constituents which account for the clinical effect seen. Likewise,
      the benefits of Yokukansan are probably attributable to the preparation as a
      whole, rather than to individual compounds.

PMID- 20812277
TI  - Amelioration of oxidative stress by dandelion extract through CYP2E1 suppression
      against acute liver injury induced by carbon tetrachloride in Sprague-Dawley
      rats.
AB  - The protective effects of common dandelion leaf water extract (DLWE) were
      investigated by carbon tetrachloride (CCl4) induced hepatitis in Sprague-Dawley
      rats. The animals were divided into five groups: normal control, DLWE control,
      CCl4 control, and two DLWE groups (0.5 and 2 g/kg bw). After 1 week of
      administering corresponding vehicle or DLWE, a single dose of CCl4 (50%
      CCl4/olive oil; 0.5 mL/kg bw) was administered 24 h before killing in order to
      produce acute liver injury. The DLWE treatment significantly decreased CCl4
      induced hepatic enzyme activities (AST, ALT and LDH) in a dose dependent manner.
      Also, the obstructed release of TG and cholesterol into the serum was repaired by
      DLWE administration. Hepatic lipid peroxidation was elevated while the GSH
      content and antioxidative enzyme activities were reduced in the liver as a result
      of CCl4 administration, which were counteracted by DLWE administration.
      Furthermore, the hepatocytotoxic effects of CCl4 were confirmed by significantly
      elevated Fas and TNF-alpha mRNA expression levels, but DLWE down-regulated these
      expressions to the levels of the normal control. Highly up-regulated cytochrome
      P450 2E1 was also lowered significantly in the DLWE groups. These results
      indicate that DLWE has a protective effect against CCl4-induced hepatic damage
      with at least part of its effect being attributable to the attenuation of
      oxidative stress and inflammatory processes resulting from cytochrome P450
      activation by CCl4.

PMID- 20812278
TI  - Mistletoe lectin-I augments antiproliferative effects of the PPARgamma agonist
      rosiglitazone on human malignant melanoma cells.
AB  - As malignant melanoma cells are highly resistant to conventional chemotherapy,
      survival rates after tumor spread remain poor and hence there is an urgent need
      for new therapeutic options. For both mistletoe lectin-I (ML-I) and the
      thiazolidinediones as synthetic ligands of the peroxisome proliferator-activated
      receptor gamma (PPARgamma) an antiproliferative effect on malignant melanoma
      cells has previously been shown. Hence, the aim of this study was to investigate
      whether the combination of ML-I and the PPARgamma ligand rosiglitazone is more
      efficacious in the treatment of malignant melanoma cells than either agent alone.
      Proliferation of three human melanoma cell lines treated with ML-I, rosiglitazone
      and the combination of both was measured in a broad concentration range (0.0001
      100 microg/mL) using the XTT cell proliferation assay. Combined application
      tremendously increased the antiproliferative effect on all three melanoma cell
      lines compared with single agent treatment. In comparison with the single use of
      rosiglitazone, the combination with ML-I significantly increased the inhibition
      of cell growth by 51-79% and in comparison with the single use of ML-I by 9-32%,
      respectively. In conclusion, this study shows that the combination of ML-I with
      rosiglitazone significantly augments their antiproliferative effect on malignant
      melanoma cells in comparison with their single agent application, which might be
      a promising tool for further therapeutic studies.

PMID- 20812279
TI  - Inhibitory effects of Hoelen extract on melanogenesis in B16/F1 melanoma cells.
AB  - Melanin synthesis is regulated by melanogenic proteins, such as tyrosinase,
      tyrosinase-related protein 1 (TRP-1) and TRP-2. The effects of Hoelen extract on
      melanogenesis were investigated in B16Fl murine melanoma cells. Specifically,
      tyrosinase activity, cell viability and melanin content were assayed, and western
      blotting and RT-PCR for tyrosinase, TRP-1 and TRP-2 conducted. The results show
      that Hoelen significantly inhibited melanin synthesis through inhibition of TRP-2
      expression, while it did not affect tyrosinase activity or its expression. Taken
      together, RT-PCR results showed that the depigmentation effect of Hoelen may be
      due to inhibition of TRP-2 gene transcription. These results suggest that Hoelen
      may be a useful inhibitor for the attenuation of melanogenesis and
      hyperpigmentation in skin cells.

PMID- 20812280
TI  - Effect of isolated fractions of Harpagophytum procumbens D.C. (devil's claw) on
      COX-1, COX-2 activity and nitric oxide production on whole-blood assay.
AB  - The present study evaluates the effect of isolated fractions of Harpagophytum
      procumbens (devil's claw) on cyclooxygenase (COX-1 and COX-2) activities and NO
      production using a whole blood assay. The activity of COX-1 was quantified as
      platelet thromboxane B(2) production in blood clotting and COX-2 as prostaglandin
      E(2) production in LPS-stimulated whole blood. Total NO(2) (-)/NO(3) (-)
      concentration was determined by Griess reaction in LPS stimulated blood. Assays
      were performed by incubation of isolated fractions obtained by flash
      chromatography monitored with HPLC, TLC and identified by (1)HNMR, containing
      different amounts of harpagoside with blood from healthy donors. Indomethacin and
      etoricoxib were the positive controls of COX-1 and COX-2 Inhibition. Data shows
      that fraction containing the highest concentration of harpagoside inhibited
      indistinctively COX-1 and COX-2 (37.2 and 29.5% respectively) activity and
      greatly inhibited NO production (66%). In contrast the fraction including iridoid
      pool increased COX-2 and did not alter NO and COX-1 activities. The fraction
      containing cinnamic acid was able to reduce only NO production (67%). Our results
      demonstrated that the harpagoside fraction is the main responsible for the effect
      of devils claw on these enzyme activities. However, other components from devil's
      claw crude extract could antagonize or increase the synthesis of inflammatory
      mediators.

PMID- 20812281
TI  - A novel Gymnema sylvestre extract stimulates insulin secretion from human islets
      in vivo and in vitro.
AB  - Many plant-based products have been suggested as potential antidiabetic agents,
      but few have been shown to be effective in treating the symptoms of Type 2
      diabetes mellitus (T2DM) in human studies, and little is known of their
      mechanisms of action. Extracts of Gymnema sylvestre (GS) have been used for the
      treatment of T2DM in India for centuries. The effects of a novel high molecular
      weight GS extract, Om Santal Adivasi, (OSA(R)) on plasma insulin, C-peptide and
      glucose in a small cohort of patients with T2DM are reported here. Oral
      administration of OSA(R) (1 g/day, 60 days) induced significant increases in
      circulating insulin and C-peptide, which were associated with significant
      reductions in fasting and post-prandial blood glucose. In vitro measurements
      using isolated human islets of Langerhans demonstrated direct stimulatory effects
      of OSA(R) on insulin secretion from human beta-cells, consistent with an in vivo
      mode of action through enhancing insulin secretion. These in vivo and in vitro
      observations suggest that OSA(R) may provide a potential alternative therapy for
      the hyperglycemia associated with T2DM.

PMID- 20812282
TI  - The differential effect of high and low molecular weight fucoidans on the
      severity of collagen-induced arthritis in mice.
AB  - Fucoidans have been extensively studied for their various biological activities
      but the exact role of fucoidans on the inflammatory processes associated with
      arthritic disease has not been studied. The effect of the treatment of high,
      medium and low molecular weight fucoidans (HMWF, MMWF and LMWF, respectively) on
      the progression of collagen-induced arthritis (CIA) was tested. A daily oral
      administration of HMWF enhanced the severity of arthritis, inflammatory responses
      in the joint cartilage and the levels of collagen-specific antibodies, while LMWF
      reduced the severity of arthritis and the levels of Th1-dependent collagen
      specific IgG(2a). Further in vitro analyses, using macrophage cell lines,
      revealed that the HMWF induced the expression of various inflammatory mediators,
      and enhanced the cellular migration of macrophages. These stimulatory effects of
      fucoidan decreased in fucoidans with lower molecular weights and LMWF did not
      exhibit any pro-inflammatory effects. Interestingly, the oral administration of
      HMWF enhanced the production of IFN-gamma, one of the Th1 cytokines, in collagen
      stimulated spleen cells that had been isolated from CIA mice, while LMWF had the
      opposite effect. These results indicate that HMWF enhances arthritis through
      enhancing the inflammatory activation of macrophages while LMWF reduces arthritis
      through the suppression of Th1-mediated Immune reactions.

PMID- 20812283
TI  - Antiinflammatory effects in THP-1 cells treated with verbascoside.
AB  - Verbascum thapsus commonly known as 'mullein' is part of a large family of
      Scrophulariaceae consisting of more than 360 species. From antiquity Verbascum
      thapsus has been used as a medicinal herb, it contains diverse polysaccharides,
      iroid glycosides, flavonoids, saponins, volatile oils and phenylentanoids.
      Inducible nitric oxide synthase (iNOS) represents one of the three isoforms that
      produce nitric oxide using L-arginine as a substrate in response to an increase
      in superoxide anion activated by NF-kB. It is implicated in different
      pathophysiological events and its expression increases greatly during an
      inflammatory process, due to oxidative stress and the activation of the enzymes
      of the antioxidant network such as SOD, CAT and GPx.In this study an inflammatory
      state was reproduced by treating THP-1 cells (human myelomonocytic leukaemia)
      with pro-inflammatory stimuli, such as LPS and IFN-gamma, obtaining an up
      regulation both in the expression and in the activity of iNOS. The aim of the
      work was to investigate the antiinflammatory action of verbascoside using a
      concentration of 100 mum. The results show a significant decrease of the
      expression and activity of iNOS, extracellular O(2) (-) production, SOD, CAT and
      GPx activity when the cells were treated with verbascoside. Based on these
      results it is hypothesized that verbascoside has antiinflammatory properties
      since it reduces the production of superoxide radicals and consequently reduces
      the activity of iNOS.

PMID- 20812285
TI  - Special focus: hybrid systems.

PMID- 20812284
TI  - Antitumour effects of Phyllanthus emblica L.: induction of cancer cell apoptosis
      and inhibition of in vivo tumour promotion and in vitro invasion of human cancer
      cells.
AB  - Phyllanthus emblica Linn. (PE) is a medicinal fruit used in many Asian
      traditional medicine systems for the treatment of various diseases including
      cancer. The present study tested the potential anticancer effects of aqueous
      extract of PE in four ways: (1) against cancer cell lines, (2) in vitro
      apoptosis, (3) mouse skin tumourigenesis and (4) in vitro invasiveness. The PE
      extract at 50-100 microg/mL significantly inhibited cell growth of six human
      cancer cell lines, A549 (lung), HepG2 (liver), HeLa (cervical), MDA-MB-231
      (breast), SK-OV3 (ovarian) and SW620 (colorectal). However, the extract was not
      toxic against MRC5 (normal lung fibroblast). Apoptosis in HeLa cells was also
      observed as PE extract caused DNA fragmentation and increased activity of caspase
      3/7 and caspase-8, but not caspase-9, and up-regulation of the Fas protein
      indicating a death receptor-mediated mechanism of apoptosis. Treatment of PE
      extract on mouse skin resulted in over 50% reduction of tumour numbers and
      volumes in animals treated with DMBA/TPA. Lastly, 25 and 50 microg/mL of PE
      extract inhibited invasiveness of MDA-MB-231 cells in the in vitro Matrigel
      invasion assay. These results suggest P. emblica exhibits anticancer activity
      against selected cancer cells, and warrants further study as a possible
      chemopreventive and antiinvasive agent.

PMID- 20812286
TI  - Multimodality imaging techniques.
AB  - In multimodality imaging, the need to combine morphofunctional information can be
      approached by either acquiring images at different times (asynchronous), and
      fused them through digital image manipulation techniques or simultaneously
      acquiring images (synchronous) and merging them automatically. The asynchronous
      post-processing solution presents various constraints, mainly conditioned by the
      different positioning of the patient in the two scans acquired at different times
      in separated machines. The best solution to achieve consistency in time and space
      is obtained by the synchronous image acquisition. There are many multimodal
      technologies in molecular imaging. In this review we will focus on those
      multimodality image techniques more commonly used in the field of diagnostic
      imaging (SPECT-CT, PET-CT) and new developments (as PET-MR). The technological
      innovations and development of new tracers and smart probes are the main key
      points that will condition multimodality image and diagnostic imaging
      professionals' future. Although SPECT-CT and PET-CT are standard in most clinical
      scenarios, MR imaging has some advantages, providing excellent soft-tissue
      contrast and multidimensional functional, structural and morphological
      information. The next frontier is to develop efficient detectors and electronics
      systems capable of detecting two modality signals at the same time. Not only PET
      MR but also MR-US or optic-PET will be introduced in clinical scenarios. Even
      more, MR diffusion-weighted, pharmacokinetic imaging, spectroscopy or functional
      BOLD imaging will merge with PET tracers to further increase molecular imaging as
      a relevant medical discipline. Multimodality imaging techniques will play a
      leading role in relevant clinical applications. The development of new diagnostic
      imaging research areas, mainly in the field of oncology, cardiology and
      neuropsychiatry, will impact the way medicine is performed today. Both clinical
      and experimental multimodality studies, in humans and animals, will have to
      demonstrate an efficient use of the imaging information provided by the
      modalities to affect the future of medical imaging.

PMID- 20812287
TI  - PET/CT in cancer research: from preclinical to clinical applications.
AB  - The identification of genetic and biochemical mechanisms underlying tumor growth
      and progression along with the unraveling of human genoma provided a plethora of
      new targets for cancer detection, treatment and monitoring. Simultaneously, the
      extraordinary development of a number of imaging technologies, including hybrid
      systems, allowed the visualization of biochemical, molecular and physiological
      aberrations linked to underlying mutations in a given tumor. In vivo evaluation
      of complex biological processes such as proliferation, apoptosis, angiogenesis,
      metastasis, gene expression, receptor-ligand interactions, transport of
      substrates and metabolism of nutrients in human cancers is feasible using PET/CT
      and radiolabeled molecular probes. Some of these compounds are in preclinical
      phases of evaluation whereas others have been already applied in clinical
      settings. Here we provide prominent examples on how some biological processes and
      target expression can be visualized by PET/CT in animal tumor models and cancer
      patients for the noninvasive detection of well-known markers of tumor
      aggressiveness, invasiveness and resistance to treatment and for the evaluation
      of tumor response to therapy.

PMID- 20812288
TI  - SPECT/CT hybrid imaging; with which CT?
AB  - AIM: The aim of this study is to show the practical use of, and to discuss the
      rationale for, high-end computed tomography (CT) integrated with intrinsic low
      resolution single-photon emission tomography (SPECT). MATERIALS AND METHODS: All
      examinations performed on three new SPECT/CT systems with diagnostic CT
      capabilities were recorded retrospectively. The use of CT was classified as low
      dose, using the CT with restraint as to the tube current and radiation dose, or
      diagnostic, with an optimum use of the CT, using CT protocols as used in ordinary
      radiological practice. The number of low-dose CT was compared with the number of
      diagnostic CT examinations. The report is based on 436 patient examinations from
      three hospitals in Norway with recently installed SPECT/CT systems, the time of
      use varying from 6 months to 2 years. The examinations performed were myocardial
      perfusion (45%), various tumors (thyroid, parathyroid, neuroendocrine 37%),
      malignant skeletal disease (12%), brain perfusion (4%), sentinel nodes in breast
      cancer (1%) and gastrointestinal bleeding (1%). RESULTS: Of the 436 patients, 431
      had a low-dose CT for attenuation correction, anatomic localisation and, also for
      diagnosis, whereas five patients had a diagnostic CT. In these series, as was
      found in recent literature, the diagnostic potential of the CT was seldom used to
      its capacity and always in predetermined diagnostic situations. CONCLUSION: There
      is a low degree of utilization of the diagnostic capabilities of the CT in the
      SPECT/CT context, for a number of reasons. This raises questions about the cost
      benefit of investing in high-end CT for SPECT/CT applications.

PMID- 20812289
TI  - Novel MRI and fluorescent probes responsive to the Factor XIII transglutaminase
      activity.
AB  - Transglutaminases, including factor XIII and tissue transglutaminase, participate
      in multiple extracellular processes associated with remodeling of the
      extracellular matrix during wound repair, blood clotting, tumor progression and
      fibrosis of ischemic injuries. The aim of this work was to evaluate a novel
      substrate analog for transglutaminase optimized by molecular modeling
      calculations (DCCP16), which can serve for molecular imaging of transglutaminase
      activity by magnetic resonance imaging and by near-infrared imaging. Experimental
      data showed covalent binding of Gd-DCCP16 and DCCP16-IRIS Blue to human clots, to
      basement membrane components and to casein in purified systems as well as in
      three-dimensional multicellular spheroids. In vivo, DCCP16 showed enhancement
      with a prolonged retention in clots and tumors, demonstrating the ability to
      detect both factor XIII and tissue transglutaminase mediated covalent binding of
      the contrast material.

PMID- 20812290
TI  - A fluorescent, paramagnetic and PEGylated gold/silica nanoparticle for MRI, CT
      and fluorescence imaging.
AB  - An important challenge in medical diagnostics is to design all-in-one contrast
      agents that can be detected with multiple techniques such as magnetic resonance
      imaging (MRI), X-ray computed tomography (CT), positron emission tomography
      (PET), single photon emission tomography (SPECT) or fluorescence imaging (FI).
      Although many dual labeled agents have been proposed, mainly for combined MRI/FI,
      constructs for three imaging modalities are scarce. Here gold/silica
      nanoparticles with a poly(ethylene glycol), paramagnetic and fluorescent lipid
      coating were synthesized, characterized and applied as trimodal contrast agents
      to allow for nanoparticle-enhanced imaging of macrophage cells in vitro via MRI,
      CT and FI, and mice livers in vivo via MRI and CT. This agent can be a useful
      tool in a multitude of applications, including cell tracking and target-specific
      molecular imaging, and is a step in the direction of truly multi-modal imaging.

PMID- 20812291
TI  - Revising the Cannabis Use Disorders Identification Test (CUDIT) by means of Item
      Response Theory.
AB  - Cannabis use among adolescents and young adults has become a major public health
      challenge. Several European countries are currently developing short screening
      instruments to identify 'problematic' forms of cannabis use in general population
      surveys. One such instrument is the Cannabis Use Disorders Identification Test
      (CUDIT), a 10-item questionnaire based on the Alcohol Use Disorders
      Identification Test. Previous research found that some CUDIT items did not
      perform well psychometrically. In the interests of improving the psychometric
      properties of the CUDIT, this study replaces the poorly performing items with new
      items that specifically address cannabis use. Analyses are based on a sub-sample
      of 558 recent cannabis users from a representative population sample of 5722
      individuals (aged 13-32) who were surveyed in the 2007 Swiss Cannabis Monitoring
      Study. Four new items were added to the original CUDIT. Psychometric properties
      of all 14 items, as well as the dimensionality of the supplemented CUDIT were
      then examined using Item Response Theory. Results indicate the unidimensionality
      of CUDIT and an improvement in its psychometric performance when three original
      items (usual hours being stoned; injuries; guilt) are replaced by new ones
      (motives for using cannabis; missing out leisure time activities; difficulties at
      work/school). However, improvements were limited to cannabis users with a high
      problem score. For epidemiological purposes, any further revision of CUDIT should
      therefore include a greater number of 'easier' items.

PMID- 20812292
TI  - Studying the relation between temporal reward discounting tasks used in
      populations with ADHD: a factor analysis.
AB  - BACKGROUND: This study aimed at investigating the relationship between tasks that
      have been used in attention deficit hyperactivity disorder (ADHD) to measure
      choices between smaller immediate and larger delayed rewards: real and
      hypothetical temporal discounting tasks, and single-choice paradigms. METHODS:
      Participants were 55 undergraduate psychology students. Tasks included a real and
      hypothetical version of a temporal discounting (TD) task with choices between a
      large reward (10 cents) after delays up to 60 seconds, and smaller immediate
      rewards (2-8 cents); two versions of a hypothetical temporal discounting task
      with choices between a large reward ($100) after delays up to 120 months, and
      smaller immediate rewards ($1-$95); a Choice Delay Task with choices between one
      point now and two points after 30 seconds (one point is worth five cents).
      RESULTS: Correlation analyses showed that the real and the hypothetical TD tasks
      with 10 cents were very strongly associated. However, the hypothetical TD tasks
      with $100 did not correlate with either the real or the hypothetical TD task with
      10 cents. Principal component analysis extracted two components: one for small
      amounts and short delays, and a second one for large rewards and long delays.
      CONCLUSIONS: Temporal reward discounting is not a uniform construct. Functional
      brain imaging research could shed more light on unique brain activation patterns
      associated with different forms of temporal reward discounting.

PMID- 20812293
TI  - Different correlations among physiological and morphological properties at single
      glutamatergic synapses in the rat hippocampus and the cerebellum.
AB  - Synapses in the mammalian central nervous system show substantial diversity in
      their physiological and morphological properties. However, the correlations among
      them have remained elusive. Here, we tried to clarify the correlations by
      establishing a method to record excitatory postsynaptic currents (EPSCs) at
      individual synapses and also to observe the morphology at the same time. A pair
      of pre- and postsynaptic neurons were labeled with different fluorescent dyes,
      and a presynaptic varicosity was selectively stimulated with a theta-tube glass
      electrode under conditions in which action potential generation was suppressed.
      Two representative types of excitatory glutamatergic synapses, one on hippocampal
      pyramidal neurons and the other on cerebellar Purkinje neurons, were studied. The
      correlations between the properties of quantal EPSCs (qEPSCs) and those of
      synaptic morphology were analyzed in rat primary culture preparations. The
      amplitude and the decay time of qEPSC were correlated with the size of the
      postsynaptic spine only at hippocampal synapses. In contrast, the size of the
      presynaptic varicosity was correlated with the size of the postsynaptic spine and
      the quantal content of evoked EPSCs only at granule neuron-Purkinje neuron
      synapses in the cerebellum. These results suggest that the interaction between
      pre- and postsynaptic structures and the coupling of postsynaptic responsiveness
      and the spine morphology differ between cerebellar and hippocampal glutamatergic
      synapses.

PMID- 20812294
TI  - Enhancement of glutamatergic transmission in the cingulate cortex in response to
      mild noxious stimuli under a neuropathic pain-like state.
AB  - Pain is evoked by noxious body stimulation or through negative emotional events
      and memories. There are several caveats to the simple proposition that pain and
      emotion are linked in the cingulate cortex (CG). In this study, we investigated
      whether mild noxious heat stimuli could affect the neuronal activity in the CG of
      rats with sciatic nerve ligation. We produced a partial sciatic nerve injury by
      tying a tight ligature in rats. Seven days after sciatic nerve ligation, rats
      received mild noxious heat stimuli. Mild noxious heat stimuli produced flinching
      behaviors in sciatic nerve-ligated rats, but not sham-operated rats. In addition,
      the mild noxious heat stimuli caused a significant increase in the release of
      glutamate in the CG of nerve-ligated rats compared with that of sham-operated
      rats. Furthermore, phosphorylated-NR1-positive cells in this area significantly
      increased after mild noxious heat stimuli under a neuropathic pain. Under this
      condition, there were no significant changes in the levels of immediate-early
      genes such as c-fos, c-jun, JunB, and Fra1 in the CG between nerve-ligated and
      sham-operated rats. However, mild noxious heat stimuli under a neuropathic pain
      like state produced a marked increase in the phosphorylated-c-jun (p-c-jun)
      immunoreactivity, which is commonly used to map neurons in the brain that can be
      activated after N-methyl-D-aspartate receptor activation. These findings raise
      the possibility that mild noxious heat stimuli under a peripheral nerve injury
      may increase the release of glutamate and promote its related postneuronal
      activity in the CG.

PMID- 20812295
TI  - Effects of solution environment on mammalian cell fermentation broth properties:
      enhanced impurity removal and clarification performance.
AB  - The processing of recombinant proteins from high cell density, high product titer
      cell cultures containing mammalian cells is commonly performed using tangential
      flow microfiltration (MF). However, the increased cellular debris present in
      these complex feed streams can prematurely foul the membrane, adversely impacting
      MF capacity and throughput. In addition, high cell density cell culture streams
      introduce elevated levels of process-related impurities, which increase the
      burden on subsequent purification operations to remove these complex media
      components and impurities. To address this challenge, an evaluation of mammalian
      cell culture broth buffer properties was examined to determine if enhanced
      impurity removal and clarification performance could be achieved. A framework is
      presented here for establishing optimized mammalian cell culture buffer
      conditions, involving trade-offs between product recovery and purification and
      improved clarification at manufacturing-scale production. A reduction in cell
      culture broth pH to 4.7-5.0 induced flocculation and impurity precipitation which
      increased the average feed particle-size. These conditions led to enhanced
      impurity removal and improved MF throughput and filter capacity for several
      mammalian systems. Feed conditions were further optimized by controlling ionic
      composition along with pH to improve product recovery from high cell density/high
      product titer cell cultures.

PMID- 20812296
TI  - Development and validation of fixed-time method for the determination of
      isoxsuprine hydrochloride in commercial dosages forms.
AB  - The main aim of this work was to develop a kinetic spectrophotometric method for
      the quantitative analysis of isoxsuprine hydrochloride in commercial tablets. The
      method is based on the reaction of isoxsuprine hydrochloride (ISx) with
      hydroxylamine hydrochloride and ammonium cerium (IV) nitrate in sulphuric acid
      medium at room temperature which resulted in the formation of yellow-coloured
      product peaking at 380 nm. The reaction is followed spectrophotometrically by
      measuring the absorbance as a function of time. Fixed time method (DeltaA = A4
      A2, where A2 and A4 refer to absorbance measurements taken at 2 and 4 min,
      respectively) was adopted for constructing the calibration curve which was found
      to be linear over the concentration range of 30-80 ugmL-1 with molar absorptivity
      of 5.95 * 103 L mol-1 cm-1. The method has been applied successfully to the
      determination of isoxsuprine hydrochloride in tablets. Statistical comparison
      (point and interval hypothesis tests) of the results showed that there is no
      significant difference between the proposed method and reference method.

PMID- 20812297
TI  - Simultaneous spectrophotometric determination of chlordiazepoxide and clidinium
      using multivariate calibration techniques.
AB  - Three multivariate modelling approaches including partial least squares
      regression (PLS), genetic algorithm-partial least squares regression (GA-PLS),
      and principal components-artificial neural network (PC-ANN) analysis were
      investigated for their application to the simultaneous determination of
      chlordiazepoxide and clidinium levels in pharmaceuticals. A set of synthetic
      mixtures of drugs in ethanol and 0.1 M HCL was made, and the prediction abilities
      of the aforementioned methods were examined using RSE% (relative standard error
      of the prediction). The PLS and PC-ANN methods were found to be comparable, and
      GA-PLS produced slightly better results. The predictive models that we built were
      successfully applied to simultaneously determine the levels of chlordiazepoxide
      and clidinium in coated tablets.

PMID- 20812298
TI  - The role of banned substance residue analysis in the control of dietary
      supplement contamination.
AB  - The potential for contaminated dietary supplements to result in a failed doping
      test remains a concern for athletes, trainers, and sporting authorities despite
      improvements to regulatory guidelines. Previous surveys of readily available
      supplements confirm that many are contaminated with steroids and stimulants
      prohibited for use in elite sport. Suggested responses to this issue include the
      complete avoidance of all supplements. Many athletes, however, use nutritional
      supplements to achieve effective training and also to ensure that daily
      nutritional requirements are met (e.g. recommended levels of vitamins and
      minerals). This ensures that the use of supplements is and will remain the norm
      for a range of sports. As a result, an alternative approach of rigorous testing
      of materials destined for use by elite athletes has been introduced in several
      countries. While the testing of final product for banned substances may help
      mitigate the problem, it will not help to remove the underlying issue of
      contamination. In this article we describe an alternative approach that uses
      appropriate quality assurance procedures backed up by testing to remove sources
      of contamination. The decrease in the incidence of contamination amongst
      supplement companies adopting such a system is explained, and contrasted with the
      relatively high incidences of contamination found in products that are not part
      of a quality system. These findings are of key importance to both supplement
      manufacturers and those involved in advising athletes about supplement use.

PMID- 20812300
TI  - Two-stage testing using selection schemes.
AB  - In this paper, we consider pooling schemes in which samples are to be tested in
      two-stages. We show that when batch size is limited as well as pool size,
      selection schemes tend to be more efficient and flexible. Formulae for the
      efficiencies of square arrays in all dimensions and for all selection schemes are
      given in the Appendix. A Fortran program has been written to find whether the
      most efficient scheme under constraints of batch and pool size be 'square' or
      'selection'.

PMID- 20812299
TI  - Enhanced spectrophotometric determination of two antihyperlipidemic mixtures
      containing ezetimibe in pharmaceutical preparations.
AB  - Two spectrophotometric methods are presented for the simultaneous determination
      of ezetimibe/simvastatin and ezetimibe/atorvastatin binary mixtures in combined
      pharmaceutical dosage forms without prior separation. The first is the derivative
      ratio method where the amplitudes of the first derivative of the ratio spectra
      ((1) DD) at 299.5 and 242.5 nm were found to be linear with ezetimibe and
      simvastatin concentrations in the ranges 0.5-20 ugml(-1) and 1-40 ugml(-1) ,
      respectively, whereas the amplitudes of the first derivative of the ratio spectra
      ((1) DD) at 289.5 and 288 nm were selected to determine ezetimibe and
      atorvastatin in the concentration ranges 5-50 ugml(-1) and 1-40 ugml(-1) ,
      respectively. The second is the H-point standard additions method; absorbances at
      the two pairs of wavelengths, 228 and 242 nm or 238 and 248 nm, were monitored
      while adding standard solutions of ezetimibe or simvastatin, respectively. For
      the analysis of ezetimibe/atorvastatin mixture, absorbance values at 226 and 248
      nm or 212 and 272 nm were monitored while adding standard solutions of ezetimibe
      or atorvastatin, respectively. Moreover, differential spectrophotometry was
      applied for the determination of ezetimibe in the two mixtures without any
      interference from the co-existing drug. This was performed by measurement of the
      difference absorptivities (DeltaA) of ezetimibe in 0.07 M 30% methanolic NaOH
      relative to that of an equimolar solution in 0.07 M 30% methanolic HCl at 246 nm.
      The described methods are simple, rapid, precise and accurate for the
      determination of these combinations in synthetic mixtures and dosage forms.

PMID- 20812301
TI  - A note on dichotomization of continuous response variable in the presence of
      contamination and model misspecification.
AB  - The purpose of this note is to raise awareness of the complexity of the practice
      involving dichotomization. It is well known that the regular regression models
      are effective tools for analyzing Gaussian-type response variables, and
      researchers are often told that it is a 'bad idea' to practice dichotomization if
      continuous measurements are available. We demonstrate through special cases,
      however, that there is another side of the story if the response variable is
      contaminated. Although dichotomization causes loss of information, it can also
      reduce input of contamination. If the reduction of contamination input outweighs
      the loss of information, analysis based on dichotomization can sometimes provide
      better results. We derive formulas of bias and variance for binary regression
      estimators under a contamination model of unknown additive errors, and compare
      them with both the least squares and robust M-estimators from the corresponding
      linear regression analysis using continuous responses. As a case study, we study
      extensively the case in which the observed response is contaminated by an error
      with a mean and a variance proportional to the mean and the variance of the
      uncontaminated true response. Conditions under which dichotomization is preferred
      are obtained. A simulation study based on a real data setting is provided, which
      supports the theoretical developments.

PMID- 20812302
TI  - A robust weighted Kaplan-Meier approach for data with dependent censoring using
      linear combinations of prognostic covariates.
AB  - The weighted Kaplan-Meier (WKM) estimator is often used to incorporate prognostic
      covariates into survival analysis to improve efficiency and correct for potential
      bias. In this paper, we generalize the WKM estimator to handle a situation with
      multiple prognostic covariates and potential-dependent censoring through the use
      of prognostic covariates. We propose to combine multiple prognostic covariates
      into two risk scores derived from two working proportional hazards models. One
      model is for the event times. The other model is for the censoring times. These
      two risk scores are then categorized to define the risk groups needed for the WKM
      estimator. A method of defining categories based on principal components is
      proposed. We show that the WKM estimator is robust to misspecification of either
      one of the two working models. In simulation studies, we show that the robust WKM
      approach can reduce bias due to dependent censoring and improve efficiency. We
      apply the robust WKM approach to a prostate cancer data set.

PMID- 20812303
TI  - Distributed lag non-linear models.
AB  - Environmental stressors often show effects that are delayed in time, requiring
      the use of statistical models that are flexible enough to describe the additional
      time dimension of the exposure-response relationship. Here we develop the family
      of distributed lag non-linear models (DLNM), a modelling framework that can
      simultaneously represent non-linear exposure-response dependencies and delayed
      effects. This methodology is based on the definition of a 'cross-basis', a bi
      dimensional space of functions that describes simultaneously the shape of the
      relationship along both the space of the predictor and the lag dimension of its
      occurrence. In this way the approach provides a unified framework for a range of
      models that have previously been used in this setting, and new more flexible
      variants. This family of models is implemented in the package dlnm within the
      statistical environment R. To illustrate the methodology we use examples of DLNMs
      to represent the relationship between temperature and mortality, using data from
      the National Morbidity, Mortality, and Air Pollution Study (NMMAPS) for New York
      during the period 1987-2000.

PMID- 20812304
TI  - Multidimensional standard curve for the development process of human fetuses.
AB  - The present paper considers a multidimensional view of the standard for the
      development process of human fetuses. An efficient method by which to find a
      multidimensional standard curve for the development process of human fetuses is
      proposed in which a logistic function with three parameters is utilized as an
      underlying model and a nonlinear regression method is applied. The proposed
      method also identifies an approximate prediction region, which can be efficiently
      applied to diagnose fetal malformation.

PMID- 20812305
TI  - Excellence, innovation and impact factor of Ultrasound in Obstetrics &
      Gynecology.

PMID- 20812306
TI  - Diabetes in pregnancy: scanning the wrong horizon?

PMID- 20812307
TI  - Phenotype of five cases of prenatally diagnosed campomelic dysplasia harboring
      novel mutations of the SOX9 gene.
AB  - OBJECTIVES: Campomelic dysplasia is a rare congenital skeletal disorder
      characterized by bowing of the long bones and a variety of other skeletal and
      extraskeletal defects, many of which can now be identified prenatally using
      advanced ultrasound equipment. The disorder is caused by mutations in SRY-box 9
      (SOX9), a gene that is abundantly expressed in chondrocytes as well as in other
      tissues. However, the correlation between genotype and phenotype is still
      unclear. We report five cases of prenatally detected campomelic dysplasia in
      which the diagnosis was confirmed by molecular analysis. METHODS: Ultrasound
      examinations were performed between 12 and 32 weeks. Standard fetal biometric
      measurements were obtained. Fetal sex was determined sonographically and
      confirmed by chromosomal analysis. Genomic DNA was obtained in four cases before
      termination of pregnancy from chorionic villi or amniocytes and in one case
      postnatally from peripheral blood. RESULTS: Skeletal dysplasia, most often limb
      shortening and bowed femora, was observed in one case in the first trimester, in
      three cases in the second trimester and in one case, presenting late for
      antenatal care, in the third trimester. Four of the pregnancies were terminated
      and one was carried to term. Postmortem/postnatal physical and radiographic
      examinations confirmed the presence of anomalies characteristic of campomelic
      dysplasia. A de novo mutation in the SOX9 gene was detected in all four cases
      that underwent termination. The father of the proband in the case that went to
      term was a carrier of a somatic mosaic mutation without clinical or radiographic
      signs of campomelic dysplasia. CONCLUSIONS: It is likely that the integrated
      expertise of ultrasonographers, obstetricians, pediatricians and clinical
      geneticists will markedly improve the likelihood of accurate prenatal clinical
      diagnoses of campomelic dysplasia. This will, in turn, encourage more specific
      molecular testing and facilitate comprehensive genetic counseling.

PMID- 20812308
TI  - Analysis and acquisition reproducibility of 3D power Doppler.

PMID- 20812310
TI  - Back to the future with influenza.

PMID- 20812312
TI  - Implications of a gap between demand and supply for rehabilitation in post
      earthquake Haiti.

PMID- 20812313
TI  - Telerehabilitation mediated physiotherapy assessment of ankle disorders.
AB  - BACKGROUND AND PURPOSE: Musculoskeletal injuries are the most common source of
      chronic pain and disability. The ankle joint is the most common of these injuries
      and without adequate rehabilitation function can be severely impaired. Access to
      physiotherapy rehabilitation services can be limited due to geographical
      remoteness and a shortage of services in rural and remote areas.
      Telerehabilitation is a potential solution to bridge this service delivery gap.
      The aim of this study was to determine the criterion validity and reliability of
      conducting a remote musculoskeletal assessment of the ankle joint complex using
      telerehabilitation technologies compared with a face-to-face assessment. METHODS:
      This study utilized a repeated measures design to assess 15 subjects (mean age
      24.5, SD 10.8 years) presenting with ankle pain. Conventional face-to-face
      assessments were compared with assessments performed via a telerehabilitation
      system. RESULTS: A similar agreement of 93.3% in patho-anatomical diagnosis and
      an 80% exact agreement (chi(2) = 4.267; p < 0.04) in primary systems diagnosis
      was found between face-to-face and telerehabilitation assessments. Clinical
      observations were found to have very strong agreement (k = 0.92) for categorical
      data and significant agreement (93.3% agreement; chi(2) = 234.4; p < 0.001) for
      binary data. A high level of inter- and intrarater reliability was found for the
      telerehabilitation assessments. CONCLUSIONS: This study demonstrates the
      criterion validity and reliability of remote musculoskeletal assessments of the
      ankle joint complex using telerehabilitation.

PMID- 20812314
TI  - Hydrogen adsorption and diffusion in p-tert-butylcalix[4]arene: an experimental
      and molecular simulation study.
AB  - Experimental adsorption isotherms were measured and computer simulations were
      performed to determine the nature of the H(2) gas uptake in the low-density p
      tert-butylcalix[4]arene (tBC) phase. (1)H NMR peak intensity measurements for
      pressures up to 175 bar were used to determine the H(2) adsorption isotherm. Weak
      surface adsorption (up to ~2 mass % H(2) ) and stronger adsorption (not exceeding
      0.25 mass % or one H(2) per calixarene bowl) inside the calixarene phase were
      detected. The latter type of adsorbed H(2) molecule has restricted motion and
      shows a reversible gas adsorption/desorption cycle. Pulsed field gradient (PFG)
      NMR pressurization/depressurization measurements were performed to study the
      diffusion of H(2) in the calixarene phases. Direct adsorption isotherms by
      exposure of the calixarene phase to pressures of H(2) gas to ~60 bar are also
      presented, and show a maximum H(2) adsorption of 0.4 H(2) per calixarene bowl.
      Adsorption isotherms of H(2) in bulk tBC have been simulated using grand
      canonical Monte Carlo calculations in a rigid tBC framework, and yield
      adsorptions of ~1 H(2) per calixarene bowl at saturation. Classical molecular
      dynamics simulations with a fully flexible calixarene molecular force field are
      used to determine the guest distribution and inclusion energy of the H(2) in the
      solid with different loadings.

PMID- 20812315
TI  - Ion dynamics in confined spaces: sodium ion mobility in icosahedral container
      molecules.

PMID- 20812317
TI  - The effect of imidazolium ionic liquid on the dehydration of fructose to 5
      hydroxymethylfurfural, and a room temperature catalytic system.

PMID- 20812316
TI  - Nucleating the assembly of macromolecular complexes.
AB  - Nature constructs intricate complexes containing numerous binding partners in
      order to direct a variety of cellular processes. Researchers have taken a cue
      from these events to develop synthetic molecules that can nucleate natural and
      unnatural interactions for a diverse set of applications. These molecules can be
      designed to drive protein dimerization or to modulate the interactions between
      proteins, lipids, DNA, or RNA and thereby alter cellular pathways. A variety of
      components within the cellular machinery can be recruited with or replaced by
      synthetic compounds. Directing the formation of multicomponent complexes with new
      synthetic molecules can allow unprecedented control over the cellular machinery.

PMID- 20812318
TI  - Increased natural killer cell cytotoxicity and NKp30 expression protects against
      hepatitis C virus infection in high-risk individuals and inhibits replication in
      vitro.
AB  - CD56(pos) natural killer (NK)/natural T (NT) cells are important innate effectors
      providing the first line of defense against viral infection. Enhanced NK activity
      has been shown to protect from human immunodeficiency virus-1 infection. However,
      the role played by these innate effectors in protection against or development of
      hepatitis C virus (HCV) infection is unknown. We characterized CD56(pos)
      populations in 11 injection drug users (IDUs) who remained uninfected despite
      being repeatedly exposed to HCV. NK profiles in exposed but uninfected (EU)
      individuals were compared with preinfection samples (median 90 days prior to HCV
      seroconversion) collected from 14 IDUs who were exposed and subsequently became
      infected (EI) and unexposed normal control subjects (n = 8). Flow cytometric
      analysis of CD56(pos) populations demonstrated that EUs had a higher proportion
      of CD56(low) mature (P = 0.0011) NK cells compared with EI subjects. Bead
      isolated NKs ( > 90% purity) from EUs had significantly higher interleukin-2 (IL
      2)-induced cytolytic activity against the NK-sensitive cell line K562 at an
      effector-to-target ratio of 10:1 (P < 0.0001). NKp30, a natural cytotoxicity
      receptor involved in NK activation, is highest on NK/NT cells in EUs relative to
      infected subjects. Using the JFH-1 infection system, we demonstrated that
      NKp30(high) cells in the absence of exogenous stimulation significantly reduce
      infection of hepatocytes. CONCLUSION: CD56(pos) populations in EUs are enriched
      for effector NKs displaying enhanced IL-2-induced cytolytic activity and higher
      levels of the natural cytotoxicity receptor NKp30-activating receptor. In
      addition, NKp30(high) cells are more effective in preventing infection of Huh-7.5
      cells than their NKp30(low/neg) counterparts. These data support the hypothesis
      that NK cells contribute to anti-HCV defense in vivo in the earliest stages of
      infection, providing innate protection from HCV acquisition.

PMID- 20812319
TI  - Hormonal acceleration of song development illuminates motor control mechanism in
      canaries.
AB  - In songbirds, the ontogeny of singing behavior shows strong parallels with human
      speech learning. As in humans, development of learned vocal behavior requires
      exposure to an acoustic model of species-typical vocalizations, and,
      subsequently, a sensorimotor practice period after which the vocalization is
      produced in a stereotyped manner. This requires mastering motor instructions
      driving the vocal organ and the respiratory system. Recently, it was shown that,
      in the case of canaries (Serinus canaria), the diverse syllables, constituting
      the song, are generated with air sac pressure patterns with characteristic
      shapes, remarkably, those belonging to a very specific mathematical family. Here,
      we treated juvenile canaries with testosterone at the onset of the sensorimotor
      practice period. This hormone exposure accelerated the development of song into
      stereotyped adultlike song. After 20 days of testosterone treatment, subsyringeal
      air sac pressure patterns of song resembled those produced by adults, while those
      of untreated control birds of the same age did not. Detailed temporal structure
      and modulation patterns emerged rapidly with testosterone treatment, and all
      previously identified categories of adult song were observed. This research shows
      that the known effect of testosterone on the neural circuits gives rise to the
      stereotyped categories of respiratory motor gestures. Extensive practice of these
      motor patterns during the sensorimotor phase is not required for their
      expression.

PMID- 20812320
TI  - Structural, electronic, and magnetoresponsive properties of triangular lanthanide
      clusters and their free-standing nitrides.
AB  - The molecular and electronic structures, stabilities, bonding features, and
      magnetoresponsive properties of three-membered [c-Ln(3)](+/0/-) (Ln = La, Ce, Pr,
      Nd, Gd, Lu) and heterocyclic six-membered [c-Ln(3)E(3)](q) (Ln = La, Ce, Pr, Nd,
      Gd, Lu; E = C, N; q = 0 or 1) rings have been investigated by means of electronic
      structure calculation methods at the DFT level. The [c-Ln(3)](+/0/-) clusters are
      predicted to be bound with respect to dissociation to their constituent atoms,
      the estimated binding energies ranging from 45.8 to 2056.4 kJ/mol. The [c-Ln(3)]
      rings capture easily a planar three-coordinated nitrogen atom at the center or
      above the center of the ring yielding the lanthanide nitride clusters [c
      Ln(3)(MU(3)-N)] adopting a planar geometry, except [c-La(3)(MU(3)-N)] which
      exhibits pyramidal geometry. The [c-Ln(3)(MU(3)-N)] clusters are predicted to be
      bound, with respect to dissociation to N ((4)S) atom and [c-Ln(3)] clusters in
      their ground states, the binding energies ranging from 53.9 to 257.9 kcal/mol.
      The six-membered [c-Ln(3)E(3)](q) rings are predicted to be bound with respect to
      dissociation to LnE(q) monomers in their ground states with dissociation energies
      in the range of 173.8 to 318.0 kcal/mol. Calculation of the NICS(zz)-scan curves
      of the clusters predicted a "hermaphrodic" magnetic response of the [c
      Ln(3)](+/0/-) and heterocyclic six-membered [c-Ln(3)E(3)](q) rings, manifested by
      the coexistence of successive diatropic (aromatic) and paratropic (antiaromatic)
      zones. The [c-La(3)](+/0/-) and [c-Lu(3)](-) are predicted to be weakly
      antiaromatic, the [c-Lu(3)](0/+), [c-Lu(3)C(3) ](+), and [c-Lu(3)N(3)] double
      (sigma+pi) aromatic, and the [c-Gd(3)C(3)] and [c-Gd(3)N(3)](+) rings
      (sigma+delta)-aromatic systems.

PMID- 20812321
TI  - Systematic benchmarking of large molecular dynamics simulations employing GROMACS
      on massive multiprocessing facilities.
AB  - The influence of the total number of cores, the number of cores dedicated to
      Particle mesh Ewald (PME) calculation and the choice of single vs. double
      precision on the performance of molecular dynamic (MD) simulations in the size of
      70,000 to 1.7 million of atoms was analyzed on three different high-performance
      computing facilities employing GROMACS 4 by running about 6000 benchmark
      simulations. Small and medium sized systems scaled linear up to 64 and 128 cores,
      respectively. Systems with half a million to 1.2 million atoms scaled linear up
      to 256 cores. The best performance was achieved by dedicating 25% of the total
      number of cores to PME calculation. Double precision calculations lowered the
      performance by 30-50%. A database for collecting information about MD simulations
      and the achieved performance was created and is freely available online and
      allows the fast estimation of the performance that can be expected in similar
      environments.

PMID- 20812322
TI  - Communications on quantum similarity, part 3: a geometric-quantum similarity
      molecular superposition algorithm.
AB  - This work describes a new procedure to obtain optimal molecular superposition
      based on quantum similarity (QS): the geometric-quantum similarity molecular
      superposition (GQSMS) algorithm. It has been inspired by the QS Aufbau principle,
      already described in a previous work, to build up coherently quantum similarity
      matrices (QSMs). The cornerstone of the present superposition technique relies
      upon the fact that quantum similarity integrals (QSIs), defined using a GTO basis
      set, depend on the squared intermolecular atomic distances. The resulting QSM
      structure, constructed under the GQSMS algorithm, becomes not only optimal in
      terms of its QSI elements but can also be arranged to produce a positive definite
      matrix global structure. Kruskal minimum spanning trees are also discussed as a
      device to order molecular sets described in turn by means of QSM. Besides the
      main subject of this work, focused on MS and QS, other practical considerations
      are also included in this study: essentially the use of elementary Jacobi
      rotations as QSM refinement tools and inward functions as QSM scaling methods.

PMID- 20812323
TI  - Can we trust docking results? Evaluation of seven commonly used programs on
      PDBbind database.
AB  - Docking is one of the most commonly used techniques in drug design. It is used
      for both identifying correct poses of a ligand in the binding site of a protein
      as well as for the estimation of the strength of protein-ligand interaction.
      Because millions of compounds must be screened, before a suitable target for
      biological testing can be identified, all calculations should be done in a
      reasonable time frame. Thus, all programs currently in use exploit empirically
      based algorithms, avoiding systematic search of the conformational space.
      Similarly, the scoring is done using simple equations, which makes it possible to
      speed up the entire process. Therefore, docking results have to be verified by
      subsequent in vitro studies. The purpose of our work was to evaluate seven
      popular docking programs (Surflex, LigandFit, Glide, GOLD, FlexX, eHiTS, and
      AutoDock) on the extensive dataset composed of 1300 protein-ligands complexes
      from PDBbind 2007 database, where experimentally measured binding affinity values
      were also available. We compared independently the ability of proper posing
      [according to Root mean square deviation (or Root mean square distance) of
      predicted conformations versus the corresponding native one] and scoring (by
      calculating the correlation between docking score and ligand binding strength).
      To our knowledge, it is the first large-scale docking evaluation that covers both
      aspects of docking programs, that is, predicting ligand conformation and
      calculating the strength of its binding. More than 1000 protein-ligand pairs
      cover a wide range of different protein families and inhibitor classes. Our
      results clearly showed that the ligand binding conformation could be identified
      in most cases by using the existing software, yet we still observed the lack of
      universal scoring function for all types of molecules and protein families.

PMID- 20812325
TI  - Large-scale, long-term nonadiabatic electron molecular dynamics for describing
      material properties and phenomena in extreme environments.
AB  - We describe the first principle-based electron force field (eFF) methodology for
      modeling the simultaneous dynamics of electrons and nuclei (eMD) evolving
      nonadiabatically under transient extreme conditions. We introduce the parallel
      implementation of eFF (pEFF) that makes it practical to perform simulations of
      the nonadiabatic dynamics of materials in extreme environments involving millions
      of nuclei and electrons, over multi-picoseconds time scales, and demonstrate its
      application to: (i) accurately determine density and predict percent ionization
      of hydrogen at high pressure (~61 GPa) and temperatures up to 15,300 K and (ii)
      determine, the single shock Hugoniot for lithium metal directly from the shock
      wave kinematics, i.e., mass velocities (U(p) ) and shock wave velocities (U(s) ),
      and shock density data. For (i), the density and ionization fractions of hydrogen
      atoms were calculated using the isobaric-isothermal ensemble at an isotropic
      pressure of 61.4 GPa and for temperatures between 300 K and 15,300 K. The results
      at 15,300 K describe a molecular fluid with density rho = 0.36 g/cm(3) , in close
      agreement with existing experiments and theory, and ~0.5% ionization. This result
      provides no indication of the existence of a critical plasma phase-transition
      point at this particular temperature and pressure, as previously predicted by
      others. For (ii), the relationship between U(p) and U(s) was characterized to be
      linear and plastic in the range 1-20 km/s, and the single shock Hugoniot was
      determined in close agreement with published results for experimentally reported
      U(p) s. In addition to this, we provide a description of the materials' behavior
      for large U(p) s in terms of the appearance of a weak metallic plasma phase by
      U(p) = 10 km/s, with ? 8% ionization, gradually transitioning to a denser plasma
      with an estimated ? 35% ionization by U(p) = 15 km/s. Last but not least, we
      confirm the computational efficiency and scalability of pEFF by comparing its
      single processor performance against the fastest existing serial code, which
      results in a linear speedup ~10* faster for every 16,000 particles in favor of
      pEFF, and by evaluating its parallel performance in terms of its strong and weak
      scaling capabilities. Our results, on Los Alamos's Lobo supercomputer (a
      38TFLOPSs Linux HPC with Quad-core AMD Opteron nodes interconnected with an
      Infiniband), show strong scaling with near ideal speedups for loads >62 particles
      per processor. Weak scaling is shown to be close to linear under the same per
      processor load range. As an absolute reference, an NVT run with 2 million
      particle lithium bulk system (0.5 M nuclei and 1.5 M electrons) on Lobo takes
      ~0.44 s/timestep on 1024 processors (~1 day/ps using an integration timestep of
      0.005 fs).

PMID- 20812324
TI  - VoteDock: consensus docking method for prediction of protein-ligand interactions.
AB  - Molecular recognition plays a fundamental role in all biological processes, and
      that is why great efforts have been made to understand and predict protein-ligand
      interactions. Finding a molecule that can potentially bind to a target protein is
      particularly essential in drug discovery and still remains an expensive and time
      consuming task. In silico, tools are frequently used to screen molecular
      libraries to identify new lead compounds, and if protein structure is known,
      various protein-ligand docking programs can be used. The aim of docking procedure
      is to predict correct poses of ligand in the binding site of the protein as well
      as to score them according to the strength of interaction in a reasonable time
      frame. The purpose of our studies was to present the novel consensus approach to
      predict both protein-ligand complex structure and its corresponding binding
      affinity. Our method used as the input the results from seven docking programs
      (Surflex, LigandFit, Glide, GOLD, FlexX, eHiTS, and AutoDock) that are widely
      used for docking of ligands. We evaluated it on the extensive benchmark dataset
      of 1300 protein-ligands pairs from refined PDBbind database for which the
      structural and affinity data was available. We compared independently its ability
      of proper scoring and posing to the previously proposed methods. In most cases,
      our method is able to dock properly approximately 20% of pairs more than docking
      methods on average, and over 10% of pairs more than the best single program. The
      RMSD value of the predicted complex conformation versus its native one is reduced
      by a factor of 0.5 A. Finally, we were able to increase the Pearson correlation
      of the predicted binding affinity in comparison with the experimental value up to
      0.5.

PMID- 20812326
TI  - Forster resonance energy transfer measurements of cofactor-dependent effects on
      protein arginine N-methyltransferase homodimerization.
AB  - Protein arginine N-methyltransferase (PRMT) dimerization is required for methyl
      group transfer from the cofactor S-adenosyl-L-methionine (AdoMet) to arginine
      residues in protein substrates, forming S-adenosyl-L-homocysteine (AdoHcy) and
      methylarginine residues. In this study, we use Forster resonance energy transfer
      (FRET) to determine dissociation constant (K(D)) values for dimerization of PRMT1
      and PRMT6. By attaching monomeric Cerulean and Citrine fluorescent proteins to
      their N-termini, fluorescent PRMTs are formed that exhibit similar enzyme
      kinetics to unconjugated PRMTs. These fluorescent proteins are used in FRET-based
      binding studies in a multi-well format. In the presence of AdoMet, fluorescent
      PRMT1 and PRMT6 exhibit 4- and 6-fold lower dimerization K(D) values,
      respectively, than in the presence of AdoHcy, suggesting that AdoMet promotes
      PRMT homodimerization in contrast to AdoHcy. We also find that the dimerization
      K(D) values for PRMT1 in the presence of AdoMet or AdoHcy are, respectively, 6-
      and 10-fold lower than the corresponding values for PRMT6. Considering that the
      affinity of PRMT6 for AdoHcy is 10-fold higher than for AdoMet, PRMT6 function
      may be subject to cofactor-dependent regulation in cells where the methylation
      potential (i.e., ratio of AdoMet to AdoHcy) is low. Since PRMT1 affinity for
      AdoMet and AdoHcy is similar, however, a low methylation potential may not affect
      PRMT1 function.

PMID- 20812327
TI  - Solvent-induced lid opening in lipases: a molecular dynamics study.
AB  - In most lipases, a mobile lid covers the substrate binding site. In this closed
      structure, the lipase is assumed to be inactive. Upon activation of the lipase by
      contact with a hydrophobic solvent or at a hydrophobic interface, the lid opens.
      In its open structure, the substrate binding site is accessible and the lipase is
      active. The molecular mechanism of this interfacial activation was studied for
      three lipases (from Candida rugosa, Rhizomucor miehei, and Thermomyces
      lanuginosa) by multiple molecular dynamics simulations for 25 ns without applying
      restraints or external forces. As initial structures of the simulations, the
      closed and open structures of the lipases were used. Both the closed and the open
      structure were simulated in water and in an organic solvent, toluene. In
      simulations of the closed lipases in water, no conformational transition was
      observed. However, in three independent simulations of the closed lipases in
      toluene the lid gradually opened. Thus, pathways of the conformational
      transitions were investigated and possible kinetic bottlenecks were suggested.
      The open structures in toluene were stable, but in water the lid of all three
      lipases moved towards the closed structure and partially unfolded. Thus, in all
      three lipases opening and closing was driven by the solvent and independent of a
      bound substrate molecule.

PMID- 20812328
TI  - Competitive dopamine receptor antagonists increase the equiactive cocaine
      concentration during self-administration.
AB  - Competitive dopamine receptor antagonists increase the rate of cocaine self
      administration. As the rate of self-administration at a particular unit dose is
      determined by the satiety threshold and the elimination half-life (t(1/2)) of
      cocaine, we investigated whether dopamine receptor antagonists altered these
      parameters in rats. The plasma cocaine concentration at the time of each self
      administration was constant during a session demonstrating that this satiety
      threshold concentration represents an equiactive cocaine concentration. The
      plasma cocaine concentration at the time of self-administration was increased by
      SCH23390, consistent with pharmacological theory. In rats trained to reliably
      self-administer cocaine, SCH23390 had no effect on the plasma steady-state
      cocaine concentration produced by constant infusions of cocaine. Therefore, this
      antagonist had no effect on cocaine t(1/2) at a dose that accelerated cocaine
      self-administration. A constant cocaine infusion at a rate that maintained steady
      state concentrations above the satiety threshold stopped self-administration.
      SCH23390, or the D2 dopamine receptor antagonist (-)eticlopride, reinstated self
      administration in the presence of the constant cocaine infusion. This is
      consistent with SCH23390 and eticlopride raising the satiety threshold above the
      steady state level produced by the constant cocaine infusion. It is concluded
      that the antagonist-induced acceleration of cocaine self-administration is the
      result of a pharmacokinetic/pharmacodynamic interaction whereby the rate of
      cocaine elimination is faster at the higher concentrations, as dictated by first
      order kinetics, so that cocaine levels decline more rapidly to the elevated
      satiety threshold. This results in the decreased interinjection intervals.

PMID- 20812329
TI  - Clinical usefulness of therapeutic drug monitoring of thiopurines in patients
      with inadequately controlled inflammatory bowel disease.
AB  - BACKGROUND: Circulating concentrations of 6-thioguanine nucleotide (6-TGN) and 6
      methyl mercaptopurine (6-MMP) are associated with thiopurine efficacy and may
      predict toxicity. This study aimed to examine retrospectively the utility of
      measuring metabolite concentrations in patients with inflammatory bowel disease
      (IBD) who had continuing symptoms despite stable thiopurine treatment. METHODS:
      Concentrations of 6-TGN and 6-MMP were measured in lysates of washed red cells by
      high-performance liquid chromatography in peripheral blood drawn from 63
      symptomatic patients with IBD (63% men, mean age 37, range 14-74 years, 67%
      Crohn's disease, 33% ulcerative colitis) treated with azathioprine or 6
      mercaptopurine. Short-term clinical outcomes were examined. RESULTS: 6-TGN
      concentrations weakly correlated with the thiopurine dose (r = 0.28, P = 0.08).
      On weight-based criteria, 50% of patients were underdosed. However, metabolite
      patterns suggested 7 (11%) patients were noncompliant, 18 (29%) were being
      underdosed, 33 (52%) were refractory to treatment with either appropriate (41%)
      or elevated (11%) metabolite concentrations, and 6 (10%) had a raised 6-MMP:6-TGN
      ratio consistent with aberrant thiopurine metabolism. The clinical outcome
      improved in 40 of 46 (87%) of patients in whom the course of action taken was as
      recommended by a metabolite-directed algorithm, while 3 of 17 patients (18%)
      improved where discordant actions were taken (P = 0.0001; Fisher's exact test).
      Fifteen patients (24%) avoided inappropriate escalation of therapy. CONCLUSIONS:
      Dose-optimization or toxicity-avoidance strategies frequently result from
      metabolite testing in patients with inadequate efficacy from thiopurines, with
      evidence of better outcomes. Thiopurine metabolite testing is a potentially
      powerful tool for optimizing thiopurine usage in IBD.

PMID- 20812330
TI  - Short pediatric Crohn's disease activity index for quality improvement and
      observational research.
AB  - BACKGROUND: Practical and objective instruments to assess pediatric Crohn's
      disease (CD) activity are required for observational research and quality
      improvement. The objectives were: 1) to determine the feasibility of completing
      the Pediatric Crohn's Disease Activity Index (PCDAI) and the Abbreviated PCDAI
      (APCDAI); and 2) to create a Short PCDAI by retaining and reweighting the most
      practical and informative components. METHODS: Physicians in the ImproveCareNow
      Collaborative for pediatric inflammatory bowel disease (IBD) were asked to record
      components of the PCDAI and assign a Physician Global Assessment (PGA) of disease
      severity at each patient encounter. We assessed the feasibility of the PCDAI, the
      APCDAI, and the individual index components by determining the proportion of
      visits in which data were recorded. We created a short index by retaining and
      reweighting components of the PCDAI completed in >=80% of visits. The feasibility
      of the Short PCDAI and its ability to discriminate between PGA categories were
      evaluated using descriptive statistics. RESULTS: This study population included
      1355 subjects with CD (6373 visits). The PCDAI and APCDAI were complete in 16.7%
      and 44.1% of visits, respectively. A Short PCDAI, including general well-being,
      abdominal pain, stools, weight, abdominal exam, and extraintestinal
      manifestations were completed in 66.5% of visits. The correlation between the
      Short PCDAI and PGA was similar to that of the PCDAI (r = 0.60, P < 0.001 versus
      0.61, P < 0.001). CONCLUSIONS: The Short PCDAI is a practical and valid tool to
      measure pediatric CD activity. Its use should facilitate quality improvement and
      observational research.

PMID- 20812331
TI  - Peripheral blood microRNAs distinguish active ulcerative colitis and Crohn's
      disease.
AB  - BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) result from
      pathophysiologically distinct dysregulated immune responses, as evidenced by the
      preponderance of differing immune cell mediators and circulating cytokine
      expression profiles. MicroRNAs (miRNAs) are small, noncoding RNAs that act as
      negative regulators of gene expression and have an increasingly recognized role
      in immune regulation. We hypothesized that differences in circulating immune
      cells in CD and UC patients are reflected by altered miRNA expression and that
      miRNA expression patterns can distinguish CD and UC from normal healthy
      individuals. METHODS: Peripheral blood was obtained from patients with active CD,
      inactive CD, active UC, inactive UC, and normal healthy adults. Total RNA was
      isolated and miRNA expression assessed using miRNA microarray and validated by
      mature miRNA quantitative reverse-transcription polymerase chain reaction.
      RESULTS: Five miRNAs were significantly increased and two miRNAs (149* and
      miRplus-F1065) were significantly decreased in the blood of active CD patients as
      compared to healthy controls. Twelve miRNAs were significantly increased and
      miRNA-505* was significantly decreased in the blood of active UC patients as
      compared to healthy controls. Ten miRNAs were significantly increased and one
      miRNA was significantly decreased in the blood of active UC patients as compared
      to active CD patients. CONCLUSIONS: Peripheral blood miRNAs can be used to
      distinguish active CD and UC from healthy controls. The data support the evidence
      that CD and UC are associated with different circulating immune cells types and
      that the differential expression of peripheral blood miRNAs may form the basis of
      future diagnostic tests for inflammatory bowel disease.

PMID- 20812332
TI  - Role of the gut-associated and secondary lymphoid tissue in the induction of
      chronic colitis.
AB  - BACKGROUND: It is well known that enteric bacterial antigens drive the
      development of chronic colitis in a variety of different mouse models of the
      inflammatory bowel diseases (IBD). The objective of this study was to evaluate
      the role of gut-associated lymphoid tissue (GALT; Peyer's patches, isolated
      lymphoid follicles), mesenteric lymph nodes (MLNs) and spleen in the pathogenesis
      of chronic colitis in mice. METHODS: Surgical as well as genetic approaches were
      used to generate lymphopenic mice devoid of one or more of these lymphoid
      tissues. For the first series of studies, we subjected recombinase activating
      gene-1-deficient mice (RAG(-/-) ) to sham surgery (Sham), mesenteric
      lymphadenectomy (MLNx), splenectomy (Splx) or both (MLNx/Splx). In a second
      series of studies we intercrossed lymphotoxinbeta-deficient (LTbeta(-/-) ) mice
      with RAG(-/-) animals to generate LTbeta(-/-) x RAG(-/-) offspring that were
      anticipated to contain functional MLNs but be devoid of GALT and most peripheral
      lymph nodes. Flow purified naive (CD4(+) CD45RB(high) ) T-cells were adoptively
      transferred into the different groups of RAG(-/-) recipients to induce chronic
      colitis. RESULTS: We found that at 3-5 wks following T-cell transfer, all four of
      the surgically-manipulated RAG(-/-) groups (Sham, MLNx, Splx and MLNx/Splx)
      developed chronic colitis that was similar in onset and severity. Flow cytometric
      analysis revealed no differences among the different groups with respect to
      surface expression of different gut-homing markers nor were there any differences
      noted in IFN-gamma and IL-17 generation by mononuclear cells isolated among these
      surgically-manipulated mice. Although we anticipated that LTbeta(-/-) x RAG(-/-)
      mice would contain functional MLNs but be devoid of GALT and peripheral lymph
      nodes (PLNs), we found that LTbeta(-/-) x RAG(-/-) mice were in fact devoid of
      MLNs as well as GALT and PLNs. Adoptive transfer of CD45RB(high) T-cells into
      LTbeta(-/-) x RAG(-/-) mice or their littermate controls (LTbeta(+/+) x RAG(-/-)
      ) induced rapid and severe colitis in both groups. CONCLUSIONS: Taken together,
      our data demonstrate that: a) neither the GALT, MLNs nor PLNs are required for
      induction of chronic gut inflammation in this model of IBD and b) T-and/or B
      cells may be required for the development of MLNs in LTbeta(-/-) mice.

PMID- 20812333
TI  - Physician assessment of ulcerative colitis activity correlates poorly with
      endoscopic disease activity.
AB  - BACKGROUND: Subjective physician assessment is the cornerstone of routine
      ulcerative colitis (UC) management. Endoscopic and histologic assessment of UC
      provides objective measures of inflammatory disease activity. The level of
      agreement between physician impression of UC activity and endoscopic disease
      activity has not been evaluated. The aim was to assess the level of agreement
      between physician's clinical impression of UC disease activity and endoscopic and
      histologic findings of inflammation. METHODS: Using the Medical Archival
      Retrieval System at the University of Pittsburgh Medical Center, we reviewed
      clinical information on all UC patients between 1995 and 2008 who had clinic
      visits recorded prior to colonoscopy. Clinical UC disease activity was defined by
      the physician's clinical impression and the endoscopic and histologic activity by
      colonoscopy with biopsy. The level of agreement between colonoscopy assessment of
      UC with histologic and clinical assessment was determined by sensitivity,
      specificity, positive and negative predictive values, and the kappa coefficient.
      RESULTS: There were 369 UC patients who had a clinic visit proximate to a
      colonoscopy. The mean age of patients was 46 +/- 16 years (50% female). The
      performance of clinical impression in recognizing disease activity, as determined
      by endoscopy, was relatively poor: sensitivity = 56.0%, predictive value negative
      = 56.8%, kappa coefficient = 0.35. In contrast, the performance of histological
      evaluation in recognizing disease activity was markedly better: sensitivity =
      93.5%, predictive value negative = 89.1%, kappa coefficient = 0.70. CONCLUSIONS:
      The physician's clinical impression of UC activity shows poor agreement with
      endoscopy and histology, with over one-third of patients with chronic
      inflammation underrecognized by clinical impression. The consequences of
      underestimated UC activity by clinical assessment may include undertreatment of
      active disease and uncontrolled chronic inflammation.

PMID- 20812334
TI  - Matrilysin-1 (MMP7) cleaves galectin-3 and inhibits wound healing in intestinal
      epithelial cells.
AB  - BACKGROUND: Galectin-3 is an animal lectin that has been implicated in wound
      healing and is decreased in inflammatory bowel disease (IBD). Matrix
      metalloproteinase-7 (MMP7), also known as matrilysin-1, a protease shown to
      cleave extracellular matrix proteins, is highly expressed in IBD tissues,
      especially at the leading edge of gastrointestinal ulcers. The ability of MMP7 to
      cleave galectin-3 and influence wound healing has not been reported previously.
      The aim was to determine whether MMP7 cleaves galectin-3 and modulates wound
      healing in intestinal epithelial cells. METHODS: The cleaved fragments of
      galectin-3 were identified by N-terminal sequencing and mass spectrometry.
      Western blotting was used to detect the cleaved galectin-3 products in a colonic
      epithelial cell line (T84 cells). Cell migration was studied by the in vitro
      scratch method. RESULTS: We demonstrate for the first time that MMP7 cleaves
      galectin-3 in vitro, resulting in three cleaved fragments (20.2 kDa, 18.9 kDa,
      and 15.5 kDa). Exogenous treatment of T84 cells with recombinant MMP7 resulted in
      the appearance of secreted galectin-3 cleavage fragments in the supernatant. MMP7
      inhibited cell migration and resulted in wound retraction and the addition of
      MMP7 to galectin-3 abrogated the wound healing and cell migration induced by
      galectin-3. CONCLUSIONS: We have demonstrated that galectin-3 is a substrate for
      MMP7. Cleavage of galectin-3 may be one mechanism by which MMP7 inhibits wound
      healing. This study has significance in understanding delayed wound healing in
      chronic intestinal diseases like intestinal ulcers and IBD, where MMP7 protein
      expression is elevated with a decreased galectin-3 protein expression.

PMID- 20812335
TI  - Real-time tool to display the predicted disease course and treatment response for
      children with Crohn's disease.
AB  - BACKGROUND: Immunomodulators and biologics are effective treatments for children
      with Crohn's disease (CD). The challenge of communicating the anticipated disease
      course with and without therapy to patients and parents is a barrier to the
      timely use of these agents. The aim of this project was to develop a tool to
      graphically display the predicted risks of CD and expected benefits of therapy.
      METHODS: Using prospectively collected data from 796 pediatric CD patients we
      developed a model using system dynamics analysis (SDA). The primary model outcome
      is the probability of developing a CD-related complication. Input variables
      include patient and disease characteristics, magnitude of serologic immune
      responses expressed as the quartile sum score (QSS), and exposure to medical
      treatments. RESULTS: Multivariate Cox proportional analyses show variables
      contributing a significant increase in the hazard ratio (HR) for a disease
      complication include female gender, older age at diagnosis, small bowel or
      perianal disease, and a higher QSS. As QSS increases, the HR for early use of
      corticosteroids increases, in contrast to a decreasing HR with early use of
      immunomodulators, early or late biologics, and early combination therapy. The
      concordance index for the model is 0.81. Using SDA, results of the Cox analyses
      are transformed into a simple graph displaying a real-time individualized
      probability of disease complication and treatment response. CONCLUSIONS: We have
      developed a tool to predict and communicate individualized risks of CD
      complications and how this is modified by treatment. Once validated, it can be
      used at the bedside to facilitate patient decision making.

PMID- 20812337
TI  - Choice of pulse sequences for magnetic resonance imaging-based semiquantitative
      assessment of cartilage defects in osteoarthritis research: comment on the
      article by Dore et al.

PMID- 20812336
TI  - Insulin-like growth factor 1 synergizes with bone morphogenetic protein 7
      mediated anabolism in bovine intervertebral disc cells.
AB  - OBJECTIVE: We undertook this study to assess the therapeutic benefits of
      intervertebral disc matrix repair and regeneration by evaluating the potential
      synergistic effect of insulin-like growth factor 1 (IGF-1) and bone morphogenetic
      protein 7 (BMP-7) on bovine spine discs and by elucidating the relevant
      molecular/cellular mechanisms. METHODS: Bovine nucleus pulposus (NP) cells were
      treated with BMP-7 and IGF-1. The subsequent anabolic effects driven by NP cells
      were assessed for proteoglycan (PG) synthesis by (35) S-sulfate incorporation and
      for PG accumulation by dimethylmethylene blue assays. Matrix formation was
      visualized by particle exclusion assay. Key matrix components and transcription
      factors were analyzed by real-time reverse transcription-polymerase chain
      reaction to determine the signaling pathways by which IGF-1 suppresses noggin, a
      potent inhibitor of BMP-7. Western blotting and nuclear translocation experiments
      were performed to assess the activation of Smad proteins. RESULTS: Stimulation of
      bovine NP cells by both IGF-1 and BMP-7 greatly potentiated anabolism through
      complementary and synergistic mechanisms on matrix formation compared with
      treatment with either growth factor alone. The exogenously added decoy ligand,
      noggin, attenuated the anabolic effects of BMP-7, and noggin was substantially
      increased by BMP-7, suggesting a negative feedback regulatory mechanism. In
      contrast, IGF-1 significantly suppressed noggin expression via the
      phosphatidylinositol 3-kinase/Akt pathway and thus potentiated BMP-7 signaling in
      bovine NP cells. Upon combination treatment, IGF-1 activated Smad2, while BMP-7
      activated Smad1/5/8 and Smad3, thus inducing all Smad signaling pathways and
      mimicking the effects of the combination of transforming growth factor beta and
      BMP-7 CONCLUSION: Combination growth factor therapy using BMP-7 and IGF-1 may
      have considerable promise in the treatment of spine disc degeneration.

PMID- 20812339
TI  - Increased muscle interstitial levels of inflammatory cytokines in polymyalgia
      rheumatica.
AB  - OBJECTIVE: Polymyalgia rheumatica (PMR) is characterized by aching of the
      proximal muscles and increased blood levels of markers of inflammation. Despite
      the muscle complaints, the current view is that symptoms are caused by
      inflammation in synovial structures. The purpose of this study was to elucidate
      the disease mechanisms in symptomatic muscles by measuring interstitial levels of
      cytokines before and after prednisolone treatment. METHODS: Twenty glucocorticoid
      naive patients newly diagnosed as having PMR and 20 control subjects were studied
      before and after 14 days of prednisolone therapy (20 mg/day). Interstitial
      concentrations of interleukin-1alpha/beta (IL-1alpha/beta), IL-1 receptor
      antagonist, IL-6, IL-8, tumor necrosis factor alpha (TNFalpha), and monocyte
      chemoattractant protein 1 were measured in symptomatic vastus lateralis and
      trapezius muscles using the microdialysis technique. Plasma levels were measured
      simultaneously. RESULTS: Prednisolone abolished symptoms in all of the PMR
      patients within 1-2 days; the erythrocyte sedimentation rate and C-reactive
      protein levels were normalized on day 14. In both muscles, interstitial
      concentrations of all cytokines were markedly higher (P < 0.05) in the PMR
      patients than in the controls before treatment. In both patients and controls,
      interstitial levels of most cytokines were higher than plasma levels, with the
      exception of IL-1alpha and TNFalpha, which were lower in both groups. In the PMR
      patients, interstitial concentrations were normalized after prednisolone
      treatment. CONCLUSION: This study introduces a novel view of PMR, indicating that
      increased interstitial levels of inflammatory cytokines in symptomatic muscles
      play a role in the pathophysiology of the disease and that cytokines may be
      released locally. To explore the disease specificity, similar studies in other
      primary inflammatory conditions are warranted.

PMID- 20812341
TI  - Sonographic appearance of heterotopic pregnancy with ruptured ectopic tubal
      pregnancy.
AB  - Heterotopic pregnancy, ie, combined intrauterine and extrauterine (ectopic)
      pregnancy, is a rare clinical entity that may present with acute abdominal
      catastrophy. Most of cases reported in literature are a consequence of medical or
      surgical interventions like assisted reproductive techniques, tubal surgeries,
      intrauterine contraceptive devices, or pelvic inflammatory disease. Heterotopic
      pregnancy occurring spontaneously is extremely uncommon. We describe the
      sonographic appearance of spontaneous heterotopic pregnancy with ruptured ectopic
      tubal pregnancy.

PMID- 20812340
TI  - Adenocarcinoma arising from colonic duplication cyst with metastasis to omentum:
      A case report.
AB  - Gastrointestinal tract duplications are uncommon congenital abnormalities.
      Carcinoma arising from duplication cyst is extremely rare, not to mention
      metastasis to other organs. We present a case of adenocarcinoma arising from a
      colonic duplication cyst with invasion of the serosa and metastasis to the
      omentum in a 40-year-old man. Duplication cysts should be included in the
      differential diagnosis of cystic masses of the gastrointestinal tract. Because
      these lesions occur so infrequently, they are often not suspected until
      encountered intraoperatively. The specific findings and advantages of sonography
      are reviewed.

PMID- 20812342
TI  - A new C-Peptide correction model used to assess bioavailability of regular human
      insulin.
AB  - The clinical assessment of new formulations of human insulin is problematic due
      to the inability to distinguish between endogenous insulin and exogenously
      administered insulin. The usual methods to surmount the problem of distinguishing
      between endogenous and exogenous human insulin include evaluation in subjects
      with no or little endogenous insulin, hyper-insulinemic clamp studies or the
      administration of somatostatin to suppress endogenous insulin secretion. All of
      these methods have significant drawbacks. This paper describes a method for C
      Peptide correction based upon a mixed effects linear regression of multiple time
      point sampling of C-Peptide and insulin. This model was able to describe each
      individual's insulin to C-Peptide relationship using the data from four different
      phase I clinical trials involving both subjects with and without type 2 diabetes
      in which insulin and C-Peptide were measured. These studies used hyper
      insulinemic euglycemic clamps or meal challenges and subjects received insulin or
      Glucagon-like peptide 1 (GLP-1). It was possible to determine the exogenously
      administered insulin concentration from the measured total insulin concentration.
      A simple statistical technique can be used to determine each individual's insulin
      to C-Peptide relationship to estimate exogenous and endogenous insulin following
      the administration of regular human insulin. This technique will simplify the
      assessment of new formulations of human insulin.

PMID- 20812347
TI  - Sorafenib induces growth inhibition and apoptosis of human chondrosarcoma cells
      by blocking the RAF/ERK/MEK pathway.
AB  - BACKGROUND: Chondrosarcoma represents the second most common primary malignant
      bone tumor causing significant morbidity due to local recurrence and limited
      treatment options. Conventional cytotoxic chemotherapy has been proven to be
      largely ineffective to this sarcoma. Here we report that sorafenib is effective
      in growth inhibition of chondrosarcoma cell lines in vitro. METHODS:
      Chondrosarcoma cell lines (SW1353 and CRL7891) were treated with sorafenib. Flow
      cytometry, DAPI assay, and Western blotting were employed to determine the
      effects of sorafenib in inhibitory proliferation and induce apoptosis in
      chondrosarcoma cells in vitro. RESULTS: The results showed that sorafenib
      effectively inhibited cell growth and induced apoptosis in chondrosarcoma cells,
      which was concurrent with inhibition of the expression of phospho-MEK and phospho
      ERK. Further more the expression levels of cyclin D1, Rb and anti-apoptotic
      proteins Bcl-xl and Mcl-1 significantly reduced, but no changes in Bcl-2 and Bax.
      We although detected the expression of Akt, JNK, p38 and their respective
      phosphoprotein, but did not found meaningful changes. CONCLUSIONS: Our findings
      demonstrate that sorafenib inhibited the Ras/Raf/MAPK pathway in a time- and dose
      dependent fashion in chondrosarcoma cell lines SW1353 and CRL7891 and suggest
      that sorafenib may be a new therapeutic option for patients with chondrosarcoma.

PMID- 20812348
TI  - Clinical value of plasma hepatocyte growth factor measurement for the diagnosis
      of periampullary cancer and prognosis after pancreaticoduodenectomy.
AB  - BACKGROUND: Previous studies suggest that serum hepatocyte growth factor (HGF)
      level may be a useful diagnostic and prognostic biomarker for various tumors. We
      investigated the utility of plasma HGF level measurements in diagnosing
      periampullary cancer (PAC). METHODS: Of the patients enrolled in this pilot study
      (n = 118), 57 had PAC, 21 had benign pancreatic tumor (BPT), 20 had chronic
      pancreatitis (CP), and 20 were healthy controls. Plasma HGF was measured with
      ELISA kits. It was measured again at 10 days and 1, 2, 3, 6, and 12 months after
      pancreaticoduodenectomy (PD). RESULTS: Plasma HGF levels were significantly
      higher in PAC patients than in BPT patients, CP patients, or healthy controls.
      When a cutoff value of 1,120  pg/ml was used, 48/57 (84%) patients with PAC were
      positive for elevated HGF, but only 6/20 (30%) of patients with CP and none of
      the controls or patients with BPT were positive for elevated HGF. After PD, HGF
      levels were significantly elevated at day 10. CONCLUSIONS: Plasma HGF level
      discriminates well between PAC and other, benign diseases. Therefore, HGF
      measurement could be a useful addition to the existing array of diagnostic tools
      for PAC pancreatic cancer. The higher postoperative value may reflect the stress
      of surgery.

PMID- 20812349
TI  - Predicting factors of unexpected peritoneal seeding in locally advanced gastric
      cancer: indications for staging laparoscopy.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study is to investigate predictive
      factors for unexpected peritoneal seeding from clinically resectable advanced
      gastric cancers to suggest the indications for staging laparoscopy (SL). METHODS:
      A total of consecutive 589 gastric cancer patients who were clinically diagnosed
      with advanced gastric cancer with no metastatic disease underwent operations at
      Seoul St. Mary's Hospital. RESULTS: A total of 72 patients (including 35 patients
      with seeding to distant peritoneum) were surgically diagnosed with peritoneal
      seeding. Borrmann type 3 (OR: 4.475) or type 4 (OR: 8.243) cancer, tumor invasion
      of T3 (OR: 2.794) or T4 (OR: 6.841) and tumor size (4  cm  <=  tumor size  <  8 
      cm; OR: 3.723 and 8  cm  <=  tumor size; OR: 6.971) were predictive factors for
      overall peritoneal seeding. Borrmann type 3 (OR: 3.524) or 4 (OR: 4.695) cancer,
      tumor invasion of T3 (OR: 4.378) or T4 (OR: 15.817), and tumors involving the
      anterior wall (OR: 2.762) also turned out to be predictive factors for distant
      peritoneal seeding. CONCLUSIONS: If SL were performed by these predictive
      factors, this should have been performed in 42.4% of advanced gastric cancers and
      the detection rates for overall peritoneal seeding would have been 24.0%.

PMID- 20812353
TI  - Emerging genes associated with the progression of nonalcoholic fatty liver
      disease.

PMID- 20812354
TI  - Beta-blockers in cirrhosis: friend and foe?

PMID- 20812355
TI  - Innate immune genetic profile to predict infection risk and outcome after liver
      transplant.

PMID- 20812356
TI  - PNPLeAse get the fats right: does lipogenesis or lipolysis cause NASH?

PMID- 20812357
TI  - Suppression of liver regeneration and hepatocyte proliferation in hepatocyte
      targeted glypican 3 transgenic mice.
AB  - Glypican 3 (GPC3) belongs to a family of glycosylphosphatidylinositol-anchored,
      cell-surface heparan sulfate proteoglycans. GPC3 is overexpressed in
      hepatocellular carcinoma. Loss-of-function mutations of GPC3 result in Simpson
      Golabi-Behmel syndrome, an X-linked disorder characterized by overgrowth of
      multiple organs, including the liver. Our previous study showed that GPC3 plays a
      negative regulatory role in hepatocyte proliferation, and this effect may involve
      CD81, a cell membrane tetraspanin. To further investigate GPC3 in vivo, we
      engineered transgenic (TG) mice overexpressing GPC3 in the liver under the
      control of the albumin promoter. GPC3 TG mice with hepatocyte-targeted,
      overexpressed GPC3 developed normally in comparison with their nontransgenic
      littermates but had a suppressed rate of hepatocyte proliferation and liver
      regeneration after partial hepatectomy. Moreover, gene array analysis revealed a
      series of changes in the gene expression profiles in TG mice (both in normal mice
      and during liver regeneration). In unoperated GPC3 TG mice, there was
      overexpression of runt related transcription factor 3 (7.6-fold), CCAAT/enhancer
      binding protein alpha (2.5-fold), GABA A receptor (2.9-fold), and wingless
      related MMTV integration site 7B (2.8-fold). There was down-regulation of insulin
      like growth factor binding protein 1 (8.4-fold), Rab2 (5.6-fold), beta-catenin
      (1.7-fold), transforming growth factor beta type I (3.1-fold), nodal (1.8-fold),
      and yes-associated protein (1.4-fold). Changes after hepatectomy included
      decreased expression in several cell cycle-related genes. CONCLUSION: Our results
      indicate that in GPC3 TG mice, hepatocyte overexpression of GPC3 suppresses
      hepatocyte proliferation and liver regeneration and alters gene expression
      profiles, and potential cell cycle-related proteins and multiple other pathways
      are involved and affected.

PMID- 20812358
TI  - Clinical syndromes and consequences of antiretroviral-related hepatotoxicity.
AB  - Highly active antiretroviral therapy (HAART)-related hepatotoxicity complicates
      the management of patients infected with human immunodeficiency virus (HIV),
      increases medical costs, alters the prescription patterns, and affects the
      guideline recommendations. Among the clinical consequences derived from HAART
      related liver toxicity, hypersensitivity reactions and lactic acidosis are
      recognized as acute events with potential to evolve into fatal cases, whereas
      there seems to be other syndromes not as well characterized but of equal concern
      as possible long-term liver complications. Belonging to the latter category of
      syndrome, HAART-related nonalcoholic steatohepatitis, liver fibrosis, portal
      hypertension, and nodular regenerative hyperplasia are discussed in this review.
      Updated information on liver toxicity of current antiretroviral drugs, including
      the most recently licensed, is provided. Management and prevention of liver
      toxicity among HIV-infected patients treated with HAART are reviewed as well.

PMID- 20812359
TI  - MicroRNA-151 and its hosting gene FAK (focal adhesion kinase) regulate tumor cell
      migration and spreading of hepatocellular carcinoma.
AB  - Recurrent chromosomal aberrations are often observed in hepatocellular carcinoma
      (HCC), but little is known about the functional non-coding sequences,
      particularly microRNAs (miRNAs), at the chromosomal breakpoints in HCC. Here we
      show that 22 miRNAs are often amplified or deleted in HCC. MicroRNA-151 (miR
      151), a frequently amplified miRNA on 8q24.3, is correlated with intrahepatic
      metastasis of HCC. We further show that miR-151, which is often expressed
      together with its host gene FAK, encoding focal adhesion kinase, significantly
      increases HCC cell migration and invasion in vitro and in vivo, mainly through
      miR-151-5p, but not through miR-151-3p. Moreover, miR-151 exerts this function by
      directly targeting RhoGDIA, a putative metastasis suppressor in HCC, thus leading
      to the activation of Rac1, Cdc42 and Rho GTPases. In addition, miR-151 can
      function synergistically with FAK to enhance HCC cell motility and spreading.
      Thus, our findings indicate that chromosome gain of miR-151 is a crucial stimulus
      for tumour invasion and metastasis of HCC.

PMID- 20812360
TI  - Hepatitis C virus nonstructural protein 5A inhibitors: novel target-now for new
      trials and new treatment strategies.

PMID- 20812362
TI  - Generation of human induced pluripotent stem cells from liver progenitor cells by
      only small molecules.

PMID- 20812363
TI  - Twelve-week posttreatment follow-up predicts a sustained virological response to
      pegylated interferon and ribavirin therapy.

PMID- 20812364
TI  - Sorafenib therapy in patients with hepatocellular carcinoma before liver
      transplantation.

PMID- 20812365
TI  - Optimal dosage of ribavirin.

PMID- 20812367
TI  - The clinical psychological diagnostic system (KPD-38): sensitivity to change and
      validity of a self-report instrument for outcome monitoring and quality
      assurance.
AB  - BACKGROUND: Monitoring psychotherapeutic progress requires valid and economic
      measures to detect change of clinical relevance. We addressed validity and
      sensitivity to change of the 'Klinisch Psychologisches Diagnosesystem 38' (KPD
      38, Clinical Psychological Diagnosis System), an instrument for outcome
      monitoring and quality assurance. METHODS: Data from an inpatient sample (n =
      1.377) were used to investigate the concurrent validity, the sensitivity to
      change, and the criterion validity of the KPD-38 in comparison to the Outcome
      Questionnaire (OQ-45) and the Brief Symptom Inventory (BSI). RESULTS: Sensitivity
      specificity analyses showed similar sensitivity and higher specificity for the
      KPD-38 scales compared with the BSI and OQ total scores. Change rates on the KPD
      38 distress scale (DIS) were found to be lower than on the BSI (KPD-38 DIS:
      36.6%, GSI: 67.7%) and the OQ-45 (KPD-38 DIS: 44.3%, OQ tot: 57.1%) total scores.
      Concordance was low with the BSI ([kappa = 0.24] and moderate with the OQ-45
      [kappa = 0.45]). DISCUSSION: Implications for applications in the field of
      outcome assessment and the challenge of further validation are discussed. The
      relation between sensitivity to change and criterion validity is highlighted.

PMID- 20812368
TI  - Efficient synthesis of an (aminooxy) acetylated-somatostatin derivative using
      (aminooxy)acetic acid as a 'carbonyl capture' reagent.
AB  - Owing to the high chemoselectivity between an aminooxy function and a carbonyl
      group, oxime ligation is one of the most preferred procedures for the preparation
      of peptide conjugates. However, the sensitivity of (aminooxy)acetylated peptides
      to ketones and aldehydes makes their synthesis and storage difficult. In our
      study, we established the efficient synthesis of an (aminooxy)acetylated
      somatostatin derivative in the presence of free (aminooxy)acetic acid, which was
      used as a 'carbonyl capture' reagent in the final cleavage step. This
      (aminooxy)acetylated compound was further used for the chemoselective ligation
      (oxime bond formation) with daunorubicin and 4-fluorobenzaldehyde leading to the
      formation of conjugates with potential applications in targeted cancer
      chemotherapy and positron emission tomography.

PMID- 20812369
TI  - Electron predators are hydrogen atom traps. Effects of aryl groups on N-C(alpha)
      bond dissociations of peptide radicals.
AB  - Effects of substituted aryl groups on dissociations of peptide aminoketyl
      radicals were studied computationally for model tetrapeptide intermediates GXD(*)
      G where X was a cysteine residue that was derivatized by S-(3-nitrobenzyl), S-(3
      cyanobenzyl), S-(3,5-dicyanobenzyl), S-(2,3,4,5,6-pentafluorobenzyl), and S
      benzyl groups. The aminoketyl radical was placed within the Asp amide group.
      Aminoketyl radicals having the S-(3-nitrobenzyl) group were found to undergo
      spontaneous and highly exothermic migration of the hydroxyl hydrogen atom onto
      the nitro group in conformers allowing interaction between these groups.
      Competing reaction channels were investigated for aminoketyl radicals having the
      S-(3-cyanobenzyl) and S-(3,5-dicyanobenzyl) groups, e.g. H-atom migration to the
      C and N atoms of the C=N group, migration to the C-4 position of the phenyl ring,
      and dissociation of the radical-activated N?C(alpha) bond between the Asp and Gly
      residues. RRKM kinetic analysis on the combined B3LYP and ROMP2/6-311++G(2d,p)
      potential energy surface indicated > 99% H-atom transfer to the C=N group forming
      a stable iminyl intermediate. The N?C(alpha) bond dissociation was negligible. In
      contrast, peptides with the S-(2,3,4,5,6-pentafluorobenzyl) and S-benzyl groups
      showed preferential N?C(alpha) bond dissociation that outcompeted H-atom
      migration to the C-4 position and fluorine substituents in the phenyl ring. These
      computational results are used to suggest an alternative mechanism for the
      quenching effect on electron-based peptide backbone dissociations of benzyl
      groups with electron-withdrawing substitutents, as reported recently.

PMID- 20812370
TI  - Furanose C-C-linked gamma-lactones: a combined ESI FTICR MS and semi-empirical
      calculations study.
AB  - Sugars that incorporate the unsaturated carbonyl motif have become important
      synthetic targets not only as a result of their potential biological properties
      but also as precursors in the synthesis of many bioactive products. Moreover,
      little is known about the influence of the gamma-lactone moiety in the
      fragmentation pattern of furanose rings. Therefore, two alpha,beta-unsaturated
      gamma-lactones (butenolides) and two beta-hydroxy gamma-lactones, C-C linked to a
      furanose ring were studied using electrospray ionization FTICR mass spectrometry.
      The behaviour of the protonated and sodiated forms of the compounds under study
      has been compared considering their structural features. Fragmentation mechanisms
      were established and ion structures were proposed taking into account the MS(2)
      and MS(3) experiments, accurate mass measurements and semi-empirical
      calculations. These inexpensive methods proved to be a valuable resource for
      proposing protonation sites and for the establishment of fragmentation pathways.

PMID- 20812371
TI  - Characterization of proteins from kernel of different soybean varieties.
AB  - BACKGROUND: Total soybean proteins, storage proteins, glycinin (11S) and beta
      conglycinin (7S) fractions and their respective subunits in seven soybean
      varieties were analyzed. In this work we also present the correlation between
      concentration and activity of bioactive proteins, lipoxygenase and proteinase
      inhibitors. RESULTS: Glycinin and beta-conglycinin comprise about 750 g kg(-1) of
      the bean storage protein and as such account for both quantity and quality of the
      kernel protein. The 11S concentration of the varieties studied ranged from 503.4
      to 602.9 g kg(-1) and those of 7S varied from 178.2 to 230.6 g kg(-1) of total
      extractable proteins. The ratio of 11S/7S proteins varied from 2.43 to 3.29 among
      the varieties. A very strong positive correlation was found between the
      concentration of Kunitz trypsin inhibitor and activity of total trypsin inhibitor
      (r = 0.96). However, lipoxygenase concentration did not show a strong correlation
      with lipoxygenase activity. CONCLUSION: It appears that among the seven ZP
      soybean genotypes there are genotypes with different amounts of subunits that
      should be bred in the future for a desired level of protein components.

PMID- 20812372
TI  - Effects of postharvest treatments on fruit quality of sweet pepper at low
      temperature.
AB  - BACKGROUND: Postharvest storage of sweet pepper fruits (Capsicum annuum L.) at
      low temperatures could impair their physical and chemical composition. Therefore,
      maintenance of essential nutrition support or altered gas exchange could preserve
      fruit quality, minimizing chilling injury. Thus our aim was to determine the
      response to postharvest application of a low concentration of nitrogen (urea) or
      antitranspirant (pinolene) during a period of 21 days at 5  degrees C. RESULTS:
      The results indicate that storage at 5  degrees C was effective with respect to
      maintaining firmness of sweet pepper fruits for 21 days, while application of
      antitranspirant increased firmness compared with non-sprayed fruits.
      Additionally, urea maintained color while increasing total phenolics and the
      activity of catalase and ascorbate peroxidase, lowering lipid peroxidation.
      Composition of free amino acids was affected to a minor extent. CONCLUSION:
      Maintaining quality is of paramount importance in the postharvest period. This
      study shows the effect of both temperature and spraying treatments with regard to
      maintaining fruit quality during this period, and provides new insights into the
      physiological role of enzymes of the antioxidant system during pepper storage at
      low temperature.

PMID- 20812373
TI  - Peptide vaccine candidates against classical swine fever virus: T cell and
      neutralizing antibody responses of dendrimers displaying E2 and NS2-3 epitopes.
AB  - Three peptide-based systems integrating B and T antigenic sites of CSFV and
      displaying the B epitopes in fourfold presentation have been designed and
      produced, and shown to bring about significant enhancements in immunogenicity
      over the peptides in monomeric form. Of the different strategies tested for
      producing the dendrimeric constructs, stepwise SPPS using 3,6-dioxaoctanoic acid
      as flexible, PEG-like spacer units at the branching points is clearly
      advantageous, in particular over ligation in solution. The constructs have been
      used for immunization of domestic pigs, in order to evaluate the protective
      response induced by each peptide constructs, and to characterize the B- and T
      cell response against CSFV in the natural host.

PMID- 20812374
TI  - Relationship between changes in the total concentration of acetic acid bacteria
      and major volatile compounds during the acetic acid fermentation of white wine.
AB  - BACKGROUND: In the scope of the wine vinegar production, this paper provides
      comprehensive information about the evolution of some volatile compounds during
      the biological acetification cycle. These data were compared with the acidity,
      cell concentration and ethanol concentration. Such information may allow a better
      understanding of the complex biological processes involved. RESULTS: The volatile
      compounds 2-phenylethanol, diethyl succinate (diethyl butanedioate), meso-2,3
      butanediol (meso-butane-2,3-diol), levo-2,3-butanediol (levo-butane-2,3-diol),
      methanol and ethyl acetate exhibited no significant changes between the starting
      wine and produced vinegar, whereas the rest [acetoin (3-hydroxybutan-2-one)
      excepted] ethyl lactate (ethyl 2-hydroxypropanoate), isoamyl alcohols (3
      methylbutan-1-ol and 2-methylbutan-1-ol), isobutanol (2-methylpropan-1-ol), 1
      propanol (propan-1-ol), and acetaldehyde were consumed in substantial amounts
      during the process. Additionally, their specific evolution patterns alongside
      bacterial cell concentrations, acidity and ethanol concentration are shown.
      CONCLUSION: Concentrations of acetic acid bacteria at the end of the
      acetification cycle were found to vary because of cell lysis, a result of the
      high acidity and low ethanol concentration of the medium. Variations were similar
      to those in some volatile compounds, which suggests their involvement in the
      metabolism of acetic bacteria. The results testify to the usefulness of this
      pioneering study and suggest that there should be interest in similar, more
      detailed studies for a better knowledge of the presence of certain volatile
      compounds and metabolic activity in cells effecting the acetification of wine.

PMID- 20812375
TI  - Aflatoxin determination in commonly consumed foods in Tunisia.
AB  - BACKGROUND: To investigate natural aflatoxin occurrence, a total of 180 samples
      of different foods widely consumed in Tunisia were analysed by an in-house
      validated high-performance liquid chromatography method including affinity column
      clean-up and post-column bromination techniques. RESULTS: The method used
      appeared to be rapid, selective and reproducible, and its performances were
      established. Detection limits were 0.05 ng g(-1) for aflatoxin B1 and 0.025 ng g(
      1) for aflatoxins B2, G1 and G2. Aflatoxins were detected in all investigated
      commodities except rice, with an overall contamination frequency of 34.4% and
      concentrations ranging from 0.1 to 40.6 ng g(-1). Aflatoxin B1 was found in all
      contaminated samples. Sorghum, spices and nuts were most contaminated.
      CONCLUSION: This study has provided an effective analytical method for the
      reliable determination of aflatoxins in food samples. Over one-third of the
      samples investigated were contaminated with aflatoxins. Sorghum, spices and nuts
      were most contaminated, whereas rice showed no contamination.

PMID- 20812376
TI  - Future directions of structural mass spectrometry using hydroxyl radical
      footprinting.
AB  - Hydroxyl radical protein footprinting coupled to mass spectrometry has been
      developed over the last decade and has matured to a powerful method for analyzing
      protein structure and dynamics. It has been successfully applied in the analysis
      of protein structure, protein folding, protein dynamics, and protein-protein and
      protein-DNA interactions. Using synchrotron radiolysis, exposure of proteins to a
      'white' X-ray beam for milliseconds provides sufficient oxidative modification to
      surface amino acid side chains, which can be easily detected and quantified by
      mass spectrometry. Thus, conformational changes in proteins or protein complexes
      can be examined using a time-resolved approach, which would be a valuable method
      for the study of macromolecular dynamics. In this review, we describe a new
      application of hydroxyl radical protein footprinting to probe the time evolution
      of the calcium-dependent conformational changes of gelsolin on the millisecond
      timescale. The data suggest a cooperative transition as multiple sites in
      different molecular subdomains have similar rates of conformational change. These
      findings demonstrate that time-resolved protein footprinting is suitable for
      studies of protein dynamics that occur over periods ranging from milliseconds to
      seconds. In this review, we also show how the structural resolution and
      sensitivity of the technology can be improved as well. The hydroxyl radical
      varies in its reactivity to different side chains by over two orders of
      magnitude, thus oxidation of amino acid side chains of lower reactivity are more
      rarely observed in such experiments. Here we demonstrate that the selected
      reaction monitoring (SRM)-based method can be utilized for quantification of
      oxidized species, improving the signal-to-noise ratio. This expansion of the set
      of oxidized residues of lower reactivity will improve the overall structural
      resolution of the technique. This approach is also suggested as a basis for
      developing hypothesis-driven structural mass spectrometry experiments.

PMID- 20812377
TI  - Diagnosis and morbidity of placenta accreta.
AB  - OBJECTIVE: To examine the diagnostic precision of ultrasound examination for
      placenta accreta in women with placenta previa and to compare the morbidity
      associated with accreta to that of previa alone. METHODS: This was a
      retrospective cohort study of all women with previa with/without accreta examined
      at the University of California, San Francisco (UCSF) between 2002 and 2008. The
      sensitivity, specificity, negative predictive value (NPV) and positive predictive
      value (PPV) of ultrasound examination for the diagnosis of accreta were
      calculated and compared with results from similar studies in the literature.
      Univariable analysis was used to compare clinical outcomes. RESULTS: The PPV of
      an ultrasound diagnosis of accreta was 68% and NPV was 98%. Ultrasound had a
      sensitivity of 89.5%. Compared with previa alone, accreta had an odds ratio (OR)
      of 89.6 (95% CI, 19.44-412.95) for estimated blood loss > 2 L, an OR of 29.6 (95%
      CI, 8.20-107.00) for transfusion and an OR of 8.52 (95% CI, 2.58-28.11) for
      length of hospital stay > 4 days. CONCLUSION: Placenta accreta is associated with
      greater morbidity than is placenta previa alone. Ultrasound examination is a good
      diagnostic test for accreta in women with placenta previa. This is consistent
      with most other studies in the literature.

PMID- 20812378
TI  - Prenatal diagnosis of crossed pulmonary arteries.

PMID- 20812379
TI  - Red mold dioscorea-induced G2/M arrest and apoptosis in human oral cancer cells.
AB  - BACKGROUND: Monascus-fermented products are among the most commonly used
      traditional food supplements. Dioscorea is known to exhibit anticancer
      properties. In this study the effects of the ethanol extract of red mold
      dioscorea (RMDE) on cell proliferation, cell cycle and apoptosis in human oral
      cancer cells were investigated. RESULTS: RMDE exercised growth inhibition on
      squamous cell carcinoma-25 (SCC-25) cells. RMDE-mediated G2/M phase arrest was
      associated with the down-regulation of NF-kappaB, resulting in the inhibition of
      cyclin B1 and CDK1 expression; this may be the mechanism by which RMDE inhibits
      cancer cells. Furthermore, the proapoptotic activity of RMDE was revealed by the
      Annexin V-FITC/PI double-staining assay. In addition, the proapoptotic effect of
      RMDE was evident by the inhibition of Bax expression in the mitochondria,
      resulting in the activation of caspase-9 and caspase-3 and subsequent triggering
      of the mitochondrial apoptotic pathway. RMDE also enhanced caspase-8 activity,
      indicating the involvement of the death receptor pathway in RMDE-mediated SCC-25
      cell apoptosis. CONCLUSION: RMDE treatment inhibited the growth of SCC-25 cells
      by arresting cell cycle at the G2/M phase and induced apoptosis in a time- and
      dose-dependent manner. Therefore RMDE may be a good candidate for development as
      a dietary supplement against oral cancer.

PMID- 20812380
TI  - Barth syndrome: an X-linked cause of fetal cardiomyopathy and stillbirth.
AB  - OBJECTIVE: Barth Syndrome (BTHS) is an X-linked multisystem disorder (OMIM
      302060) usually diagnosed in infancy and characterized by cardiac problems
      [dilated cardiomyopathy (DCM) +/- endocardial fibroelastosis (EFE) +/- left
      ventricular non-compaction (LVNC)], proximal myopathy, feeding problems, growth
      retardation, neutropenia, organic aciduria and variable respiratory chain
      abnormalities. We wished to determine whether BTHS had a significant impact on
      fetal and perinatal health in a large cohort of family groups originating from a
      defined region. METHOD: Case note review on 19 families originating from the UK
      and known to the Barth Syndrome Service of the Bristol Royal Hospital for
      Children. RESULTS: Details are presented on six kindreds (32%) with genetically
      and biochemically proven BTHS that demonstrate a wider phenotype including male
      fetal loss, stillbirth and severe neonatal illness or death. In these families, 9
      males were stillborn and 14 died as neonates or infants but there were no losses
      of females. BTHS was definitively proven in five males with fetal onset of DCM +/
      hydrops/EFE/LVNC. CONCLUSION: These findings stress the importance of
      considering BTHS in the differential diagnosis of unexplained male hydrops, DCM,
      EFE, LVNC or pregnancy loss, as well as in neonates with hypoglycemia, lactic
      acidosis and idiopathic mitochondrial disease.

PMID- 20812381
TI  - Taste and aroma of fresh and stored mandarins.
AB  - During the last decade there has been a continuous rise in consumption of fresh
      easy-to-peel mandarins. However, mandarins are much more perishable than other
      citrus fruit, mainly due to rapid deterioration in sensory acceptability after
      harvest. In the current review we discuss the biochemical components involved in
      forming the unique flavor of mandarins, and how postharvest storage operations
      influence taste and aroma and consequently consumer sensory acceptability. What
      we perceive as mandarin flavor is actually the combination of basic taste, aroma
      and mouth-feel. The taste of mandarins is principally governed by the levels of
      sugars and acids in the juice sacs and the relative ratios among them, whereas
      the aroma of mandarins is derived from a mixture of different aroma volatiles,
      including alcohols, aldehydes, ketones, terpenes/hydrocarbons and esters. During
      postharvest storage and marketing there is a gradual decrease in mandarin sensory
      acceptability, which has been attributed to decreases in acidity and typical
      mandarin flavor, paralleling an accumulation of off-flavor. Biochemical analysis
      of volatile and non-volatile constituents in mandarin juice demonstrated that
      these changes in sensory acceptability were concomitant with decreases in acidity
      and content of terpenes and aldehydes, which provide green, piney and citrus
      aroma on the one hand, and increases in ethanol fermentation metabolism products
      and esters on the other, which are likely to cause 'overripe' and off-flavors.
      Overall, we demonstrate the vast importance of the genetic background, maturity
      stage at harvest, commercial postharvest operation treatments, including curing,
      degreening and waxing, and storage duration on mandarin sensory quality.

PMID- 20812382
TI  - Effect of caffeic acid on haemoglobin-mediated lipid and protein oxidation in
      washed cod mince during ice and frozen storage.
AB  - BACKGROUND: Little is known about the relation between haemoglobin (Hb)-mediated
      lipid and protein oxidation in muscle foods and how these two reactions can be
      inhibited by naturally occurring antioxidants. This study was aimed at evaluating
      (1) lipid oxidation and protein oxidation induced by 20 umol L(-1) Hb during
      chilled and frozen storage of washed cod mince and (2) the efficiency of 10-1000
      ppm (0.063-6.3 mmol L(-1)) caffeic acid in preventing these reactions. RESULTS:
      Addition of 20 umol L(-1) Hb increased peroxide value (PV), rancid odour, protein
      carbonylation, protein insolubilisation, redness loss and alpha-tocopherol loss
      in ice-stored washed cod mince. Since both lipid and protein oxidation developed
      at the same time, it was not possible to conclude which reaction initiated the
      other. All studied reactions were efficiently inhibited by >= 50 ppm caffeic
      acid, which could be a result of alpha-tocopherol regeneration, general radical
      scavenging, reduced formation of oxidised Hb forms and/or conformational changes
      in Hb structure. During frozen storage the only clear effect of Hb was increased
      PV, and here caffeic acid was less efficient as an antioxidant. CONCLUSION: Hb
      induced lipid and protein oxidation occurred quickly in ice-stored washed cod
      mince, and the two reactions could not be separated in time. During frozen
      storage, Hb caused only limited lipid oxidation. Caffeic acid (>=50 ppm) was an
      efficient antioxidant during ice storage.

PMID- 20812383
TI  - Disruption of PMR1 in Kluyveromyces lactis improves secretion of calf
      prochymosin.
AB  - BACKGROUND: Chymosin is an important industrial enzyme widely used in cheese
      manufacturing. Kluyveromyces lactis is a promising host strain for expression of
      the chymosin gene. However, only low yields of chymosin (80 U mL(-1) in shake
      flask culture) have been obtained using K. lactis GG799. The aim of this study
      was to increase the amount of recombinant calf chymosin secreted by K. lactis
      GG799 by disrupting the PMR1 gene. RESULTS: Kluyveromyces lactis GG799 harbouring
      the disrupted PMR1 gene showed reduced growth in ethylene glycol tetraacetic acid
      containing and Ca(2+) -deficient medium, but Ca(2+) supplementation eliminated
      the growth problem. The calf chymosin gene was ligated into the K. lactis GG799
      expression vector, generating the plasmid pKLAC1-N-prochymosin. The linearised
      plasmid was homologously integrated into the genome of K. lactis GG799. In shake
      flask culture, chymosin activity was 496 U mL(-1) in the K. lactis PMR1-deficient
      mutant, sixfold higher than that in wild-type K. lactis GG799. CONCLUSION:
      Disrupting the PMR1 gene improved chymosin production in K. lactis GG799 sixfold.
      This knowledge could be applied to industrial chymosin production.

PMID- 20812384
TI  - Changes in saccharide, amino acid and S-methylmethionine content during malting
      of barley grown with different nitrogen and sulfur status.
AB  - BACKGROUND: Changes in saccharide, amino acid and S-methylmethionine (SMM)
      concentrations and enzyme activities during the malting of barley grown with
      different nitrogen (N) and sulfur (S) supplementation were investigated in order
      to clarify their relationship with N and S fertiliser levels. RESULTS:
      Concentrations of N and S in barley grain were significantly increased by the
      addition of N to the culture soil. Application of N decreased the starch
      concentration in grain. On the other hand, higher N fertilisation increased the
      beta-glucan concentration in grain and malt, thus decreasing the accessibility of
      beta-glucanase to its substrates. Proteolytic enzyme activity was significantly
      higher in the absence (-N treatment) than in the presence (+N treatment) of N
      fertiliser, making the concentration of the majority of amino acids in malt
      slightly higher in the - N treatment. SMM was synthesised in grain after
      imbibition, and application of N increased the SMM content in malt. CONCLUSION:
      Although SMM can be controlled to a certain extent during kilning, a balanced
      supply of N and S during cultivation can also be helpful for the production of
      malt with lower SMM concentration. Adequate soil management is desirable to
      maintain the balance between good agronomic performance and high malt quality.

PMID- 20812385
TI  - Characterisation of proteolytic enzymes from muscle and hepatopancreas of fresh
      water prawn (Macrobrachium rosenbergii).
AB  - BACKGROUND: Fresh water prawn in Thailand is widely consumed due to its delicacy.
      During postmortem handling and storage, prawn meat becomes soft and mushy,
      probably as a result of indigenous proteases. Therefore, an understanding of
      prawn proteases associated with the degradation of muscle proteins from fresh
      water prawn could pave the way for prevention of such a phenomenon during
      extended storage. RESULTS: Proteolytic enzymes in the crude extract (CE) from
      muscle and hepatopancreas of fresh water prawn (Macrobrachium rosenbergii) were
      characterised. CE from muscle exhibited the highest hydrolytic activities towards
      haemoglobin at pH 5 and 50  degrees C, while that from hepatopancreas had the
      highest activity on casein at pH 7 and 60  degrees C. Based on inhibitor study,
      cysteine protease and serine protease were dominant in CE from muscle and
      hepatopancreas, respectively. CE from muscle rarely hydrolysed natural actomyosin
      (NAM), but could not degrade pepsin-soluble collagen (PSC). Conversely, NAM and
      PSC were susceptible to hydrolysis by CE from hepatopancreas as evidenced by the
      marked decreases in band intensity. Activity staining using haemoglobin, casein
      and gelatin as substrates revealed that no proteolytic or gelatinolytic activity
      was observed in CE from prawn muscle, while CE from hepatopancreas exhibited
      pronounced hydrolytic activities towards all substrates. CE from muscle showed
      calpain and cathepsin L activities but CE from hepatopancreas mainly exhibited
      tryptic and chymotryptic activities. CONCLUSION: Serine proteases, mainly trypsin
      like or chymotrypsin-like, from hepatopancreas were probably responsible for the
      softening of prawn meat during postmortem storage via the degradation of both
      muscle and connective tissues.

PMID- 20812387
TI  - CDC issues Q&A on ART and HIV transmission. 'Undetectable viral load does not
      mean...no virus'.

PMID- 20812386
TI  - N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) for predicting
      silent myocardial ischaemia in type 2 diabetes mellitus independent of
      microalbuminuria.
AB  - BACKGROUND: In the early identification of cardiovascular risk, it is essential
      to establish a biological marker for cardiac complications that is comparable to
      albuminuria for nephropathy. We tested the hypothesis that N-terminal pro-brain
      natriuretic peptide (NT-proBNP) might be a marker for silent myocardial ischaemia
      in diabetes. METHODS: In forty consecutively recruited subjects without evident
      coronary artery disease, serum NT-proBNP was measured together with multi-slice
      computed tomography. With patients suspected of having significant coronary
      artery stenosis by multi-slice computed tomography, coronary angiography was
      performed. Silent myocardial ischaemia was defined as the presence of significant
      coronary artery stenosis with more than 50% luminal narrowing by angiography.
      RESULTS: Thirteen patients (32.5%) had silent myocardial ischaemia. NT-proBNP
      levels were significantly higher in these patients (181.1 +/- 43.8 versus 55.2 +/
      9.7 pg/mL, p < 0.005) but HbA(1c), lipid profiles, and creatinine were similar
      in the two groups. Moreover, log NT-proBNP was identified as an independent
      predictor of silent myocardial ischaemia (R(2) = 0.502, p < 0.05) after
      adjustment for HbA(1c), creatinine, albuminuria, hypertension, hyperlipidaemia,
      or smoking. After stratifying patients by NT-proBNP, the upper tertile compared
      to the lowest tertile was significantly associated with silent myocardial
      ischaemia (odds ratio: 26.7, p < 0.05). Receiver operation characteristics
      analysis with a cut-off value of 52 pg/mL showed 92% sensitivity and 75%
      specificity for predicting silent myocardial ischaemia (positive predictive value
      64.7%, negative predictive value 94.3%). CONCLUSIONS: The outstandingly high
      negative predictive value of NT-proBNP enables us to focus on diabetic patients
      with occult coronary disease, independently of microalbuminuria.

PMID- 20812388
TI  - Awareness.  HIV prevention campaign must take changing sexual trends into
      account.

PMID- 20812389
TI  - SSI.  HIV did not affect man's ability to perform sedentary work.

PMID- 20812390
TI  - Prisons.  Inmate made false statements about lack of HIV medication.

PMID- 20812391
TI  - HIV and TB: Dual immunosuppressive diseases.

PMID- 20812392
TI  - Converting blood sugar to HbA1c.

PMID- 20812393
TI  - Steroids and the heart.

PMID- 20812394
TI  - Exercise no trigger for defibrillator shocks.

PMID- 20812395
TI  - Ask the doctor.  I have tried all of the statin drugs to lower my cholesterol,
      but each one has caused severe muscle pain.  Are there any non-statin medications
      I could try using to lower my cholesterol?

PMID- 20812396
TI  - Cochlear osteoneogenesis after meningitis in cochlear implant patients: a
      retrospective analysis.
AB  - STUDY DESIGN: Retrospective clinical study. SETTING: Academic tertiary referral
      center at the Medical University of Hannover. PATIENTS: Computed tomographic
      findings of 126 patients (95 children and 31 adults) profoundly deafened by
      meningitis during a period of 20 years were evaluated. Children were defined as
      up to 12 years old at the onset of meningitis. No patients showed any relevant
      bilateral auditory brainstem response thresholds at the time of admission to our
      clinic. INTERVENTIONS: Patient histories, surgical findings, and imaging results
      were analyzed by experienced surgeons/neuroradiologists. RESULTS: Of 95 children,
      30 (32%) displayed symptoms of labyrinthitis ossificans, whereas 11 (36%) of 31
      adults showed changes of the bony structure of the cochlea. High-resolution
      computed tomography (HRCT) evaluation indicated that the ossification was
      detected more frequently if there was a larger time interval between onset of
      meningitis and high-resolution computed tomographic scan. Bilateral ossification
      at various stages was observed in 67% of children and 55% of adults with
      obliteration. In the comparison of cochlear ossification found in computed
      tomographic scans and intraoperative obliteration, HRCT showed a specificity of
      73% and a sensitivity of 88%. The intraoperative evaluation revealed various
      stages of cochlear obliteration in 44% of children and 39% of adults. CONCLUSION:
      In our study, the earliest onset of labyrinthitis ossificans was found in high
      resolution computed tomographic scans as early as 4 weeks after the onset of
      meningitis. In most cases, ossification occurred bilaterally with predominantly
      asymmetric involvement of both ears. The rate of osteoneogenesis increases
      significantly over time after meningitis. This leads to the conclusion that
      cochlear ossification can start very early and increase over time with
      unpredictable speed. Cochlear ossification typically develops bilaterally. From
      these results, we conclude that cochlear implantation should be performed
      bilaterally as soon as possible after meningitis and deafness have been
      diagnosed. HRCT offers good specificity but only limited sensitivity.
      Preoperative diagnostics should include magnetic resonance imaging to optimize
      preparation for cochlear implantation.

PMID- 20812397
TI  - You're a published author!

PMID- 20812401
TI  - Are we living in a novel age?

PMID- 20812410
TI  - Pessimism about pedophilia.  There is no cure, so the focus is on protecting
      children.

PMID- 20812404
TI  - Ratio of metastatic lymph nodes to total number of nodes resected is prognostic
      for survival in esophageal carcinoma.
AB  - INTRODUCTION: The role of the number of metastatic nodes in esophageal cancer
      surgery is of interest. We assess predictors of survival after oesophagectomy for
      esophageal and gastroesophageal junction malignancy. METHODS: Prospective data of
      consecutive patients undergoing oesophagectomy and systematic lymphadenectomy
      between 1991 and 2007. RESULTS: Of 224 patients, 148 patients (66%) had
      adenocarcinoma, 70 (31%) squamous cell carcinoma, and 6 (2.6%) were other tumor
      types. Five-year survival was 43% with hospital mortality of 3.5%. Locoregional
      recurrence occurred in 14%. The total number of affected nodes significantly
      reduced survival (four or more metastatic nodes). Further analysis of the ratio
      of nodes affected to the total number resected showed a significant decrease in
      survival as the percentage of positive nodes increased (p < 0.001). CONCLUSIONS:
      Patients undergoing surgery for esophageal cancer should be staged according to a
      minimum total number of metastatic lymph nodes and ratios because this more
      accurately predicts survival than current staging systems.

PMID- 20812412
TI  - The evolving understanding of stigma.  Theories differ about why it is so
      pervasive and so hard to eradicate.

PMID- 20812411
TI  - Dementia syndromes in the elderly.  Alzheimer's disease is most common, but other
      diagnoses are possible.

PMID- 20812413
TI  - Treating depression along with alcohol dependence.

PMID- 20812414
TI  - How will national health care reform affect my mental health coverage?  Does this
      new law nullify the parity bill that was supposed to take effect this year?

PMID- 20812415
TI  - Heat can beat the heart.  Play it safe in hot, humid weather--it can overheat the
      heart.

PMID- 20812416
TI  - Eating can cause low blood pressure.  Postprandial hypotension can show up as
      dizziness or falling after a meal.

PMID- 20812417
TI  - Potential salt assault. A weighty proposal calls for the FDA to help Americans
      shake the salt habit.

PMID- 20812419
TI  - Tape of meetings eases jitters before bypass.

PMID- 20812418
TI  - When and how to treat a leaky mitral valve.  Symptoms, heart measurements guide
      the need for mitral valve surgery.

PMID- 20812420
TI  - Ask the doctor. I have rheumatoid arthritis, and my doctor wants me to take
      prednisone for it. Will this drug be bad for my blood pressure, which is already
      high?

PMID- 20812421
TI  - Ask the doctor. A year ago, I had an orchiectomy for prostate cancer; my PSA is
      now 0.74. Not long afterward, I had two cardiac stents implanted. I still have
      some angina and shortness of breath. I started Ranexa a couple of weeks ago,
      which helps my angina. Do you have any suggestions for my heart since I no longer
      make testosterone, which I understand helps protect men's hearts and arteries.

PMID- 20812422
TI  - When the pie is too small.

PMID- 20812423
TI  - International Conference on Harmonisation; guidance on Q4B Evaluation and
      Recommendation of Pharmacopoeial texts for use in the International Conference on
      Harmonisation Regions; Annex 12 on Analytical Sieving General Chapter;
      availability. Notice.
AB  - The Food and Drug Administration (FDA) is announcing the availability of a
      guidance entitled "Q4B Evaluation and Recommendation of Pharmacopoeial Texts for
      Use in the ICH Regions; Annex 12: Analytical Sieving General Chapter." The
      guidance was prepared under the auspices of the International Conference on
      Harmonisation of Technical Requirements for Registration of Pharmaceuticals for
      Human Use (ICH). The guidance provides the results of the ICH Q4B evaluation of
      the Analytical Sieving General Chapter harmonized text from each of the three
      pharmacopoeias (United States, European, and Japanese) represented by the
      Pharmacopoeial Discussion Group (PDG). The guidance conveys recognition of the
      three pharmacopoeial methods by the three ICH regulatory regions and provides
      specific information regarding the recognition. The guidance is intended to
      recognize the interchangeability between the local regional pharmacopoeias, thus
      avoiding redundant testing in favor of a common testing strategy in each
      regulatory region. This guidance is in the form of an annex to the core guidance
      on the Q4B process entitled "Q4B Evaluation and Recommendation of Pharmacopoeial
      Texts for Use in the ICH Regions" (the core ICH Q4B guidance).

PMID- 20812424
TI  - Abstracts of the 10th Annual European Round Table on Fabry Disease: Evolving
      Standards in Fabry Disease. Prague, Czech Republic. October 16-17, 2009.

PMID- 20812425
TI  - Medical malpractice: on-call status plus medical advice equals physician-patient
      relationship. Mead v Legacy Health System, No. A130969 (Or. App. October 28,
      2009).

PMID- 20812426
TI  - Medical malpractice: defendant may be liable for the lifelong extraordinary cost
      of raising a disabled child. Wilkie v Aslam, Civil Action No. BPG-08-1425 (D. Md.
      October 21, 2009).

PMID- 20812427
TI  - Small businesses and the Affordable Care Act of 2010.
AB  - The Patient Protection and Affordable Care Act (ACA) includes several short- and
      long-term provisions designed to help small businesses pay for and maintain
      health insurance for their workers, and to allow workers without employer
      coverage to gain access to affordable, comprehensive health insurance. Provisions
      include a small business tax credit to offset premium costs for firms that offer
      coverage starting this taxable year, establishment of state-based insurance
      exchanges that promise to lower administrative costs and pool risk more broadly,
      and creation of new market rules and an essential benefit standard to protect
      small firms and their workers. Analysis shows that up to 16.6 million workers are
      in firms that would be eligible for the tax credit in 2010 to 2013. Over the next
      10 years, small businesses and organizations could receive an estimated $40
      billion in federal support through the premium credit program.

PMID- 20812428
TI  - Litigation: setting aside default judgement is an extraordinary remedy. Black v
      United States, Civil Action No. 5:09-CV-51-KKC (E.D. Ky. November 12, 2009).

PMID- 20812429
TI  - Negligent infliction of emotional distress: expert testimony not necessary to
      prove negligent infliction of emotional distress. Thornton v Garcini, No. 107028
      (Ill. October 29, 2009).

PMID- 20812430
TI  - Medical malpractice: absconding plaintiff's counsel leads to a conundrum. NC-DSH,
      Inc. v Garner, No. 49029 (Nev. October 29, 2009).

PMID- 20812431
TI  - Bivalirudin use during radiofrequency catheter ablation procedures in two
      patients with a history of heparin-induced thrombocytopenia.
AB  - Current guidelines recommend using bivalirudin, a direct thrombin inhibitor,as a
      preferred alternative to unfractionated heparin in patients with heparin induced
      thrombocytopenia (HIT) for percutaneous coronary intervention, as well as for
      cardiac and vascular surgery. Anticoagulation during radiofrequency catheter
      ablation (RFA) procedures may be another potential use for bivalirudin in the
      setting of HIT. Radiofrequency catheter ablation procedures involving left atrial
      or left ventricular access are increasingly employed as a method to treat cardiac
      arrhythmias. Because stroke risk is a serious complication of RFA,
      anticoagulation is required during this procedure. We describe the first report,
      to our knowledge, of successful use of bivalirudin anticoagulation during RFA
      procedures in two patients with a history of clinically diagnosed HIT that
      precluded the use of unfractionated heparin or low-molecular-weight heparin. One
      of the patients underwent RFA for ventricular tachycardia, the other for
      pulmonary vein isolation for the treatment of atrial fibrillation. In both
      patients, bivalirudin was administered as a 0.75-mg/kg intravenous bolus,
      followed by a 1.75-mg/kg/hour infusion.Activated clotting time (ACT) was measured
      after the initial bolus in each patient. However, no dosage adjustment was made
      based on the ACT, and the infusion rate of bivalirudin remained fixed during the
      procedures. Both procedures were completed without any embolic events. No
      bleeding or clotting events were noted; one patient experienced minor access site
      oozing that was not felt to be clinically important. Bivalirudin is a therapeutic
      option for anticoagulation during left-sided catheter RFA procedures in patients
      with a history of HIT.

PMID- 20812432
TI  - The 21st century prosthodontist.

PMID- 20812433
TI  - Meropenem-induced vanishing bile duct syndrome.
AB  - Vanishing bile duct syndrome (VBDS) is a rare and potentially life-threatening
      disorder in which progressive destruction and disappearance of small intrahepatic
      bile ducts occur, with resultant cholestasis. The mechanism by which biliary
      epithelial cells are damaged and intrahepatic bile ducts are lost has not been
      fully elucidated. However, many etiologies have been reported,and several drugs
      have been implicated. Meropenem is a widely used, well tolerated broad-spectrum
      carbapenem antibiotic indicated for the treatment of intraabdominal infections,
      complicated skin and skin structure infections, and pediatric bacterial
      meningitis. We describe what we believe is the first reported case of meropenem
      induced VBDS. A 60-year-old woman was diagnosed with VBDS after being treated
      with meropenem for a left temporal lobe brain abscess. Three weeks after starting
      the drug, the patient developed mixed hepatocellular and cholestatic liver injury
      with jaundice and pruritus.Meropenem-induced liver injury was suspected, and the
      drug was discontinued. Diagnostic tests ruled out other causes of cholestasis,
      including infectious and immunologic conditions. A liver biopsy, performed due to
      persistent liver injury, demonstrated an absence of bile ducts, which, in
      conjunction with the patient's clinical course, was consistent with the diagnosis
      of VBDS. Several months after the cessation of meropenem, the patient's liver
      function test results improved. Use of the Naranjo adverse drug reaction
      probability scale indicated a probable relationship (score of 6)between the
      patient's development of VBDS and meropenem therapy. A high index of suspicion is
      necessary to diagnose VBDS and other types of drug induced liver injury.
      Clinicians should consider VBDS as a potential diagnosis in patients receiving
      meropenem who have prolonged cholestasis, especially after other more probable
      causes have been excluded.

PMID- 20812434
TI  - External validity: a forgotten issue?

PMID- 20812435
TI  - Falsely elevated tacrolimus levels caused by immunoassay interference secondary
      to beta-galactosidase antibodies in an infected liver transplant recipient.
AB  - Careful interpretation of tacrolimus levels is essential to ensure optimal
      immunosuppressive therapy while avoiding toxicity. Interference with tacrolimus
      assays may be an underreported event that has the potential to result in negative
      patient outcomes through unnecessary modifications of therapy. We describe a 55
      year-old liver transplant recipient who had falsely elevated tacrolimus levels
      that led to the eventual disruption of his immunosuppressive therapy and
      subsequent rejection of his allograft.Although his increased tacrolimus levels
      did not correlate with clinical signs and symptoms of tacrolimus toxicity,
      interruption of therapy in this patient was supported by an acute infection and a
      slight elevation in serum creatinine concentration. Tacrolimus levels were
      analyzed by using an antibody conjugated magnetic immunoassay method, and levels
      as high as 79.7 ng/ml were observed, despite discontinuation of tacrolimus. We
      conducted an evaluation for assay interference by using an alternative assay
      method(microparticle enzyme immunoassay), by testing plasma samples that were not
      hemolyzed, and by analyzing levels of an unrelated drug that uses the same
      technology as the initial tacrolimus assay. beta-galactosidase antibodies were
      ultimately confirmed as the cause of the immunoassay interference. Inpatients
      receiving tacrolimus, spuriously high tacrolimus levels should be carefully
      evaluated, and drastic adjustments to therapy should be made only within the
      context of clinical toxicity.

PMID- 20812436
TI  - A Starr-Edwards mitral prosthesis after 44 years of good performance.
AB  - The Starr-Edwards caged-ball prosthesis has been widely used to replace cardiac
      valves. The Model 6120 mitral prosthesis was introduced on the market in 1965 to
      reduce the high incidence of ball variance and thromboembolism of the previous
      model. We report the case of a Starr-Edwards Model 6120 which had been in place
      for 44 years and was still well functioning with no apparent structural damage.

PMID- 20812437
TI  - Blunt renal trauma and the predictors of failure of non-operative management.
AB  - OBJECTIVES: While non-operative management of renal trauma in selected patients
      is now an accepted management option, predictors of failure of this treatment
      strategy are still unclear. METHODS: Five-year retrospective study of all
      patients with blunt renal injuries managed non-operatively at a Level I Trauma
      Center. Abstracted data included patient demographics, initial vital signs, base
      deficit, associated injuries, use of blood transfusion, management, and outcomes.
      Patients with successful non-operative management (S-NOM) and failure of non
      operative management (F-NOM) were compared with two-tailed Student's t test,
      Fisher's exact test, or chi-square analysis as appropriate. RESULTS: Over five
      years, 271 patients out of 12,252 trauma cases (2.2%) had blunt renal injury; 239
      (88%) were initially managed non-operatively, and ten (4.1%) of these patients
      later requiring operation or intervention. No differences in age, sex, initial
      vitals, or GCS were found between S-NOM and F-NOM. The F-NOM patients were more
      seriously injured than the S-NOM patients (ISS 31 vs. 21, p < 0.001); had worse
      acidosis (ABG base deficit of-9.1 vs. -4.5, p < 0.001); required more blood
      products (12 units PRBC vs. 2.6 units PRBC, p < 0.001); and had significantly
      longer hospital lengths of stay (37 days vs. 12 days, p < 0.001). Angiography was
      used more frequently in the F-NOM patients (40% vs. 8.7%, p < 0.02). In the F-NOM
      only 3 (30%) required direct kidney intervention: 1 nephrectomy, 1 open urinoma
      drainage and 1 open nephrostomy tube placement. All of these patients had grade V
      renal injuries. The rest of the F-NOM patients had operative interventions not
      directly related to their renal injuries: 1 splenectomy and 6 missed bowel
      injuries. CONCLUSION: Non-operative management of blunt renal injuries is
      successful in most cases. Patients with a high base deficit, ongoing transfusion
      requirements, and greater Injury Severity Scores have a higher likelihood of
      requiring operation, but these procedures most often are to address non-renal
      abdominal injuries. High-grade blunt renal injuries that are hemodynamically
      stable can be treated expectantly on an individual basis with close follow-up.
      Any patient with hemodynamic instability, renal pedicle injury, renal artery
      thrombosis, or urinary extravasation will likely require operative intervention.

PMID- 20812438
TI  - I see dead people. Hypothyroid myopathy and hypothyroid psychosis.

PMID- 20812439
TI  - Be part of the solution.

PMID- 20812440
TI  - "Draumatized".

PMID- 20812441
TI  - Breast cancer in Mississippi: what can we do?
AB  - Although the incidence and death rate from breast cancer are trending downward in
      the United States, the death rate in Mississippi, especially in African
      Americans, is still one of the highest. Physicians and other health care
      professionals should work closely with their patients to help modify life styles,
      encourage prevention strategies, and vigorously follow the American Cancer
      Society guidelines for the early detection of breast cancer. Finding breast
      cancer in its earliest, most treatable stage is our best hope.

PMID- 20812442
TI  - Evidence-based medicine guidelines in obstetrics/gynecology and trauma surgery.
AB  - The purpose of this study was to compare the use of evidence based medicine in
      the guidelines published by the American College of Obstetrician and
      Gynecologists (ACOG) and Trauma Surgery (Eastern Association for Trauma Surgery
      [East]). We compared the references and the types of recommendations in ACOG and
      EAST guidelines. Odds ratio (OR), along with 95% confidence intervals (CI) were
      calculated and 95% CI not crossing the integer 1 were considered significant.
      Over eight years (1998-2005), ACOG published 58 guidelines and EAST, 23. Among
      the references cited, randomized clinical trials (RCT) were noted in 17%
      (714/4225) for ACOG versus 9% (165/1850) among trauma surgery guidelines (OR
      2.07; 95% 1.74, 2.48). ACOG guidelines were also significantly more likely to
      have recommendations based on RCT (29%; 135/464) than EAST (10%, 24/242; OR 3.73,
      95% CI 2.34, 5.94). East and ACOG guidelines have significantly fewer RCT and
      recommendations based on them than previously thought.

PMID- 20812443
TI  - Mississippi burnout. Part I: Personal characteristics and practice context.
AB  - Research suggests that practice conditions can predict burnout, which is an
      important factor in physician performance and career choices. Understanding the
      personal characteristics and practice contexts that heighten burnout risk is a
      first step toward interventions that could minimize burnout. This study describes
      how burnout differs, across characteristics and contexts, among a sample of
      Mississippi physicians. Data are from an online survey of all licensed
      Mississippi physicians with unique email addresses. Roughly one-quarter of
      physicians responding to the burnout question reported burnout and more than half
      reported feeling stressed. Middle-aged (40-59) physicians report higher levels of
      burnout than their younger and older counterparts. Physicians who are self
      employed also report higher levels of burnout than salaried physicians.
      Physicians reporting regional perceived workforce shortages, especially in mental
      health practices, also reported significantly higher burnout levels. We discuss
      the implications of our findings for devising strategies to reduce burnout and
      retain qualified health care providers for Mississippi residents.

PMID- 20812444
TI  - The broken heart.

PMID- 20812445
TI  - Doctors asked to be vigilant in following novel H1N1 vaccination recommendations.

PMID- 20812446
TI  - One picture is not worth a thousand pages.

PMID- 20812447
TI  - The Grits Report 2009: America's physicians face their D-day and Mississippi's
      docs tell Obama that "Caps work!".

PMID- 20812448
TI  - Body composition data for individuals 8 years of age and older: U.S. population,
      1999-2004.
AB  - OBJECTIVES: This report presents body composition data from whole body dual
      energy x-ray absorptiometry scans for persons 8 years of age and older who
      participated in the National Health and Nutrition Examination Survey (NHANES)
      1999-2004. Valid total body measurements were obtained on 16,973 individuals.
      Through the use of multiple imputation, a useable sample of 22,010 individuals
      was achieved for analysis. Measures for the total body and regions of the body
      include total mass, fat mass, percentage fat, lean soft tissue (excluding bone
      mineral content), and fat-free mass (including bone mineral content). METHODS:
      Means, standard errors, and selected percentiles were calculated for the total
      body and for regions of the body by sex, race and ethnic, and age population
      subgroups. Standard errors of the mean were estimated by Taylor Series
      Linearization, which incorporates sample weights and accounts for the NHANES
      complex sample design. RESULTS: Females had higher percentage body fat and fat
      mass than males. After age 11 years, males had higher lean tissue and fat-free
      mass than females. Percentage body fat was lowest at ages 16-19 years among males
      and at ages 8-15 years among females. Among males, non-Hispanic white persons had
      greater fat mass than either Mexican American or non-Hispanic blacks. Among
      females, non-Hispanic black persons had greater fat mass than either Mexican
      American or non-Hispanic whites. Mexican-American males and females had less lean
      soft tissue than either non-Hispanic white or non-Hispanic black males and
      females. Among both males and females, lean soft tissue and fat-free mass were
      lowest at ages 8-11 years.

PMID- 20812449
TI  - [Neurologic and psychiatric implications of apathy].
AB  - During his long practice as head physician of a neurological and psychiatrical
      department with over 100 beds performed the examination and department of more
      than a hundred thousand patients. Based on the acquired experience and the data
      of the most recent literature he treats every aspect of the apathy syndrome. He
      emphasizes the multidisciplinary approach during both establishing the causes and
      the examination and treatment of patients. In order to clarify the diagnosis
      consultations with other disciplines must be used as well as the the knowledge
      provided by the now essential CT, MRI, PET, SPECT. The author discusses the
      international therapeutical possibilities and practice after the recently alredy
      possible exact diagnosis.

PMID- 20812450
TI  - [Prophylactic migraine treatment with topiramate].
AB  - Migraine is a very common disorder characterized by the combination of typical
      headache with associated autonomic symptoms and ranked by the WHO as number 19
      among all diseases worldwide causing disability. Considerable progresses have
      been made in recent years to understand the pathophysiology of migraine, which
      has led to improved treatment options for the acute migraine attack as well as
      migraine prophylaxis. When headaches are frequent or particularly severe,
      prophylactic therapy should be considered, however preventive treatment is often
      insufficient to decrease migraine frequency substantially or is not well
      tolerated. The present paper summaries the possible drug treatment options which
      have the A level of evidence for effective preventive therapy of migraine.
      Summarises the evidences for the prophylactic migraine treatment, specially the
      role of the newly approved topiramate in the prophylaxis.

PMID- 20812451
TI  - [Immune responses and neuroimmune modulation in the pathogenesis of acute
      ischemic stroke and poststroke infections].
AB  - Acute-onset cerebrovascular diseases are connected to a number of immunological
      changes. Here, we summarize immune responses participating in the evolution of
      atherosclerotic plaques and poststroke local immune responses in the injured CNS
      as well as in the systemic circulation. Ischemic injury of the CNS alters the
      balanced neuroimmune modulation resulting in CIDS, the central nervous system
      injury-induced immune deficiency syndrome. Due to the immunodepression and
      reduced pro-inflammatory immune responses, the susceptibility for infection is
      increased; indeed, poststroke infection plays a major role in stroke-related
      mortality. On the other hand, CIDS may protect against damaging autoimmune
      responses elicited by exposed CNS antigens. Investigation of immune responses
      related to ischemic stroke may result in novel therapies indicated by an
      increasing number of experimental and clinical trials altering poststroke immune
      responses and preventing infections.

PMID- 20812452
TI  - [The effect of Stalevo-dosing on quality of life of Parkinsonian patients with
      wearing-off].
AB  - In Stalevo tablets, used in the therapy of patients with Parkinson's disease,
      levodopa is combined with decarboxylase inhibitors and COMT inhibitors to provide
      a more steady plasma concentration of levodopa. Previously several study has
      shown, that the better pharmacokinetic profile decreases the fluctuation of motor
      and non-motor symptoms. Better control of symptoms improves quality of life.
      Ideal blood levels of levodopa however can only be achieved by multiple daily
      dosing. This may be uncomfortable, may decrease compliance, thereby influence
      quality of life. To evaluate this, an observational follow-up study was
      undertaken in Hungary in 2007, among patients who were given Stalevo -
      independently of this study - because of signs of decrease in the duration of
      drug effect (wearing off). Patients got Stalevo in three, four or five daily
      divided dosages, the results were assesed after three months. The study included
      223 patients (ITT population), of whom 208 (PP population) responded regarding
      quality of life on both visits. Statistical analysis of the results showed that
      treatment significantly decreased symptoms of wearing off (wearing off card with
      19 items) and improved quality of life (EQ-5D and VAS quality of life scale)
      regardless of the frequency of dosing.

PMID- 20812453
TI  - [New surgical technique for atlanto-axial instability: C1-2 dorsal fixation with
      the screw-rod system].
AB  - OBJECTIVE: It is still challenging to perform the operation for the instability
      of the C1-C2 junction because of the limited cases, unique anatomical landmarks,
      the potential or real injury of the neurological elements, the serious clinical
      state and the special technical and human background is demanding. With the aim
      of minimalize the risk the following method provide sufficient stability,
      successful and simple. METHOD: The authors used the dorsally implanted screw-rod
      systems for operating 34 patient with C1-2 instability resulting clinically signs
      and symptoms. Depending the anatomical landmarks and the technical possibilities,
      the screw insertion method and the reinforced wire cable use was selected.
      Meaning the indication of the surgical treatment, the neurological signs,
      compromise of the spinal canal and pain resisting the conservative treatment was
      presented. RESULT: The C1-2 dorsally fixation was performed to 34 patients. Both
      sided lateral mass screw was inserted in 30 cases (88.3%). Because of the
      anatomical landmarks in four cases (11.7%) the one sided screwing was made by the
      Magerl technique. Pure bone quality detecting intraoperatively demand
      reinforcement with titanium cables for three cases (8.8%). Pain resulted of
      instability was recovered. The clinical and neurorariological follow-up present
      perfect result for 26 patients (76%), good result for six patients, there was
      respectable result for two patients. Most of the patients, 31 cases (91%) were
      satisfied, and three patients (9%) consider their condition acceptable.
      CONCLUSION: Performing the represened techique, the risk and the time of the
      operation was decreased reducing the rate of the complications. The method
      providing full stability resulted immediate axial painless, no outer support and
      early mobilization is possibile. Summarizing this technique is safe, reliable and
      cost effective.

PMID- 20812454
TI  - [Endangered future: education and replacement of specialists in neurology--a
      survey in Hungary, 2010].
AB  - Lack of neurologists has become an obvious problem recently in Hungary, not only
      in small hospitals, but in major health care centers and also in university
      hospitals. With the current survey we set forth to estimate the number of board
      certified neurologists, and to evaluate the foreseeable changes in the next
      decade. In the beginning of 2010 there were 1310 physicians in Hungary with an
      official license to practice neurology. During 2009 neurological performance at
      least once during the year was claimed to the National Health Insurance Fund by
      948 board certified neurologists. The number of those neurologists who are
      routinely involved in neurological patient care was estimated to be around 750.
      The lack of the young generation is characteristic for the age distribution of
      neurologists. In nine out of the 19 counties of Hungary the number of
      neurologists below the age of 35 is one or nil. In the ten-year period of 2000
      2009 the annual mean number of new board certifications in neurology was 22. This
      number is much lower than that needed to replace those who get employed abroad
      and who leave the system for other reasons. The number of neurologists in the age
      range of 40-60 years will drop to 2/3 of the current number by 2020 even if
      emigration of neurologists will completely halt. If emigration will continue at
      the current rate and the number of those in neurological training will not
      increase considerably, then by 2020 only about 300 neurologists will have to
      cover neurological services throughout Hungary. As this number is insufficient
      for the task, and the tendency is clearly foreseeable, the health care government
      should urgently react to this situation to ensure an acceptable level of
      neurological services in the near future for the population of Hungary.

PMID- 20812455
TI  - Clinical, radiological and genetic aspects of leukodystrophies.
AB  - The authors summarize the pathomechanism of the myelination process, the
      clinical, radiological and the genetical aspects of the leukodystrophies, as in
      18q deletion syndrome, adrenoleukodysrtophy, metachromatic leukodystrophy,
      Pelizaeus-Merzbacher leukodystrophy, Alexander disease and olivo-ponto-cerebellar
      atrophy (OPCA).

PMID- 20812456
TI  - [Needed collaboration in neurosurgery--status quo in beginning of 2010].

PMID- 20812457
TI  - [Statement of SMBOE OTT--about chronic cerebrospinal insufficiency in multiple
      sclerosis].

PMID- 20812458
TI  - Now for the really hard part: implementing health reform.

PMID- 20812459
TI  - Community benefit: overcoming organizational barriers and laying the foundation
      for success.

PMID- 20812460
TI  - Electronic medical records and cost efficiency in hospital medical-surgical
      units.
AB  - This study examines the impact of electronic medical records (EMRs) on cost
      efficiency in hospital medical-surgical units. Using panel data on California
      hospitals from 1998 to 2007, we employed stochastic frontier analysis (SFA) to
      estimate the relationships between EMR implementation and the cost inefficiency
      of medical-surgical units. We categorized EMR implementation into three stages
      based on the level of sophistication. We also examined the effects of specific
      EMR systems on cost inefficiency. Our SFA models addressed potential bias from
      unobserved heterogeneity and heteroskedasticity. EMR Stages 1 and 2, nursing
      documentation, electronic medication administration records, and clinical
      decision support were associated with significantly higher inefficiency.

PMID- 20812461
TI  - Medical spending differences in the United States and Canada: the role of prices,
      procedures, and administrative expenses.
AB  - The United States far outspends Canada on health care, but the sources of
      additional spending are unclear. We evaluated the importance of incomes,
      administration, and medical interventions in this difference. Pooling various
      sources, we calculated medical personnel incomes, administrative expenses, and
      procedure volume and intensity for the United States and Canada. We found that
      Canada spent $1589 per capita less on physicians and hospitals in 2002.
      Administration accounted for the largest share of this difference (39%), followed
      by incomes (31%), and more intensive provision of medical services (14%). Whether
      this additional spending is wasteful or warranted is unknown.

PMID- 20812462
TI  - Health care when workers need it most: before and after entry into the Social
      Security Disability Insurance Program.
AB  - This study analyzed survey data on Social Security Disability Insurance (SSDI)
      beneficiaries during the six-year window surrounding SSDI entitlement to
      illustrate changes in characteristics, insurance status, and health care access.
      We found that SSDI beneficiaries were less likely to be insured than the general
      working-age population, even three years before SSDI entitlement, and their
      uninsurance rates remained high until the third year after SSDI entitlement.
      Health care access problems were reported frequently during all periods
      surrounding SSDI entitlement, and poverty rates increased markedly post
      entitlement. The findings suggest that there are significant gaps in the safety
      net for disabled workers before, during, and after the transition to SSDI.

PMID- 20812463
TI  - Rural and urban differences in children's Medicaid and CHIP participation.
AB  - Efforts to increase enrollment in Medicaid and the Children's Health Insurance
      Program (CHIP) among uninsured children would benefit from an understanding of
      how program participation varies in rural and urban areas. Using Current
      Population Survey data from the period 2006-2007, rural participation rates were
      slightly higher than urban rates in the nation overall. There was no rural-urban
      difference when comparisons were based on within-state variation, independent of
      adjustment for individual characteristics. For researchers examining health
      policy issues strongly influenced by state policies or other state-level factors,
      this study highlights the challenges presented by national data sets with small
      or nonexistent samples from geographic areas within some states.

PMID- 20812464
TI  - Low-income Medicare beneficiaries and their experiences with the part D
      prescription drug benefit.
AB  - This study seeks to understand how much beneficiaries knew about the Medicare
      prescription drug benefit (Part D) and low-income subsidy (LIS) programs and what
      their experiences were with the programs. Part D enrollees who automatically
      qualified for the LIS were less likely to report awareness that they could switch
      among different plans, had lower knowledge scores, and were more likely to have
      medications not covered by the plan compared to beneficiaries who applied for the
      LIS and others who enrolled in Part D but did not receive the LIS. Communication
      efforts to the LIS population, particularly for beneficiaries deemed
      automatically eligible for the LIS, need to continually make them aware of their
      benefits and protections in Part D.

PMID- 20812465
TI  - Rummaging for a final theory.

PMID- 20812466
TI  - Lunar pencil lead.

PMID- 20812467
TI  - Undifferentiated ethics.

PMID- 20812468
TI  - Fat attack.

PMID- 20812469
TI  - Social analgesics.

PMID- 20812470
TI  - Sour showers.

PMID- 20812471
TI  - Doubts on dispersants.

PMID- 20812472
TI  - Quantum light switch.

PMID- 20812473
TI  - Snake oil in the supermarket.

PMID- 20812474
TI  - The deepening crisis.

PMID- 20812475
TI  - Democracy's laboratory.

PMID- 20812476
TI  - A year of living dangerously.

PMID- 20812477
TI  - Eternal fascinations with the end.

PMID- 20812478
TI  - Why can't we live forever?

PMID- 20812479
TI  - When does life belong to the living?

PMID- 20812480
TI  - Dust to dust.

PMID- 20812482
TI  - Good riddance.

PMID- 20812481
TI  - Last of their kind.

PMID- 20812483
TI  - How much is left?

PMID- 20812484
TI  - Laying odds on the apocalypse.

PMID- 20812485
TI  - Could time end?

PMID- 20812486
TI  - What comes next.

PMID- 20812487
TI  - How does geothermal drilling trigger earthquakes?

PMID- 20812488
TI  - [Jewish cemtery and Barzilai emergency room in Ashkelon].

PMID- 20812489
TI  - [National health index].
AB  - Recently, a booklet presenting a national health index was published by the
      Israel Medical Association (IMA]. The publication of an objective tool for the
      measurement and evaluation of the health of the population in Israel and the
      assessment of the healthcare system is an important and valued action. A tool of
      this sort, which analyzes the situation of the healthcare system relative to that
      of other countries in the world and allows for international comparisons-- is
      necessary for the promotion of a public debate on health and medical issues in
      Israel and serves as a useful tool for decision-makers. In this work, certain
      difficulties are delineated regarding the choice of factors and variables that
      comprise the national health index published--specifically in the significance
      accorded to the selected parameters and methodology upon which the Index was
      determined. The creation of a suitable national health index requires additional
      work necessitating, first and foremost, the integration of a methodology that
      correctly reflects the state of health and healthcare in Israel. An international
      comparison is also required--one which will be evaluated based on the determined
      methodology and the chosen parameters. The detailing of these issues serves to
      ensure a reliable and quality database, so that among other uses, it may serve
      its important purpose as a national health index that determines short and long
      term goals, for the setting of priorities and for the tracking of trends and
      directions of development. Thereby, it would contribute to the improvement and
      promotion of the health of the residents of the State of Israel.

PMID- 20812490
TI  - [The quality indigators program in Clalit Health Services: the first decade].
AB  - The quality indicators program in the community has existed in Clalit Health
      Services for over a decade. As a part of this program, approximately 70 evidence
      based quality indicators have been defined, in 11 different domains. The
      indicators relate to preventive medicine (immunizations, early detection of
      diseases, e.g. colorectal cancer, breast cancer, hypertension, chronic renal
      failure), chronic disease management (diabetes, hyperlipidemia, ischemic heart
      disease, asthma, congestive heart failure), care of the elderly (prevention of
      repeated hospitalizations) and child care (obesity detection, anemia detection
      and treatment). The indicators program is founded on one of the worldwide leading
      information systems, based on a common data warehouse with data regarding
      sociodemographic factors, purchase of medications, health services utilization,
      laboratory and imaging data, as well as a unique, validated registry of chronic
      diseases. The program has led to progress in several domains, including control
      of diabetes and hyperlipidemia, pneumococcal vaccination and early detection of
      colorectal cancer. The program narrowed the gaps and reduced inequalities between
      the Arab and Jewish populations, and between socioeconomic levels. The
      improvement in quality indicators is based on teamwork of physicians, nurses,
      other health professionals and administrative staff. The day-to-day work and the
      major effort invested in Clalit's enrollees are reflected in the continuing
      improvement in clinical quality.

PMID- 20812491
TI  - [Equity promotion in Maccabi Healthcare Services: from the Equality Report to an
      organizational action plan].
AB  - Maccabi Healthcare Services (MHS), the second largest HMO in Israel, has chosen
      to implement a multi-annual strategy to promote equality and equity in
      healthcare. Within the strategy's framework, MHS will maintain an ongoing process
      of studying the variability of its members characteristics for the purpose of
      adjusting service provision and improving health outcomes. MHS has recently
      published its first Equality Report, dedicated to defining the observed
      associations between its members demographic and socioeconomic characteristics
      and their health measures. The report identifies those sub-groups belonging to
      Israel's geographic and social peripheries that require focused interventions.
      Based on the report's recommendations, MHS has decided to designate promotion of
      equality as its strategic objective, a filter through which every policy decision
      will be reviewed. In addition it was decided to: 1. develop an organizational
      methodology to produce an index to assess reductions in disparities over time; 2.
      adjust MHS services to member's ethnic and cultural needs; 3. strengthen
      perceptions of community orientation based in primary care; 4. target resources
      to "social peripheries", beginning in 2010; 5. improve service accessibility and
      availability in geographically peripheral areas; 6. reduce economic barriers to
      healthcare. This article details the disparities as analyzed in the report in
      addition to the specific policy decisions made in their wake.

PMID- 20812492
TI  - [Minors visits (ages 14-18) at primary clinics without an accompanying guardian:
      attitudes of primary care physicians of Clalit Health Services - South District].
AB  - BACKGROUND: According to Israeli law, for a minor to receive medical treatment,
      the physician is obligated to obtain informed consent from the minor's parents.
      In practice, minors under the age of 18 often attend the clinics on their own. In
      past years, only a few attempts have been made to revise the law, however, none
      were implemented. STUDY AIMS: To evaluate the attitudes and knowledge of
      physicians in primary care clinics regarding the legal aspects of minors' visits
      at the clinics, relating to how widespread is the phenomena, the influencing
      factors, the physician's opinion and approach. METHODS: A descriptive study based
      on self-administered questionnaires that were distributed by post during 2005, to
      primary care physicians belonging to Clalit Health Services, south district. The
      questionnaires included demographic details, attitudes and knowledge of minors'
      visits. RESULTS: Analysis of 103 questionnaires found that minors attending
      clinics without their parent is a common phenomenon. The reasons noted were:
      acquaintance with the parents, and that their children are "mature enough". The
      physician's knowledge about the Israeli law on the subject was found to be
      deficient: 56% answered incorrectly to questions on which the law is very clear,
      and in most of the other questions many claimed they did not know the correct
      answer. Many of the physicians think that minors should not visit the clinic by
      themselves; only 6% attended an educational program related to this matter.
      CONCLUSIONS: The subject of minors attending clinics without an accompanying
      parent warrants discussion, and clear and updated legislation. In addition, as
      stems from the study, there is a need to update physicians regarding this issue.

PMID- 20812494
TI  - [Does the transition to clinical training change students' perception of career
      choice, physician's character and preclinical studies?].
AB  - BACKGROUND: In Israel, the transition to clinical training in hospitals is the
      first direct encounter of the medical student with the reality of the profession.
      This is a significant socialization step for his upcoming professional decisions.
      AIMS: This study aimed to identify how this encounter influences students'
      perceptions of career choice, physician's character and preclinical studies.
      METHODS: Fourth year Israeli medical students at the Tel Aviv University
      voluntarily completed a questionnaire before and after their first clinical
      clerkship. The questionnaire was comprised of 30 5-point Likert scale statements
      and 3 multiple choice questions with the possibility to add remarks. RESULTS: The
      random response rate was 90% (81/90) before the clerkship and 82% (90/110) at its
      end. Results indicate that the students are satisfied with their medical studies
      at both junctures. However, after the clerkship, 23% of the students consider
      alternatives to clinical medicine compared with only 6% before, and 16% would
      rethink studying medicine. Physicians are perceived as professional,
      compassionate, respectful to colleagues and actively participating in students'
      education. Physicians' levels of workload and bitterness are evaluated as high
      and moderate, respectively, while their levels of reward and satisfaction with
      medicine are evaluated as low and moderate, respectively. Their evaluation of the
      contribution of preclinical studies as preparation for clinical studies had not
      changed after the clerkship and was moderate, and earlier exposure to patients
      and clinical relevancy of the learned subjects were preferred. SUMMARY AND
      DISCUSSION: The students enter the medical world highly satisfied, and this
      feeling shall be maintained until the stage of being independent physicians and
      choosing their specialties. The picture that evolved, in which a high proportion
      of the students consider alternatives to clinical medicine, is disappointing.
      Educators should be aware of their role model function not only in knowledge and
      skills, but also in behavior and communication with patients. The students
      pointed to necessary changes in the medical curriculum to make basic sciences
      more relevant to clinical medicine. A broader study at different stages of
      studies in the rest of the medical faculties in Israel may be needed.

PMID- 20812493
TI  - [A prospective study to evaluate the safety of minor cutaneous surgery during
      aspirin treatment].
AB  - BACKGROUND: Many patients undergoing cutaneous surgery are treated with aspirin
      due to its proven advantages. Discontinuation of aspirin prior to surgery is
      still controversial. We conducted a large-scale, prospective study to evaluate
      the safety of dermatologic surgery in patients receiving aspirin. OBJECTIVES: The
      authors' objectives were to evaluate the complication rate in patients undergoing
      cutaneous surgery while treated with aspirin. METHODS: All patients operated on
      solely by one plastic surgeon were included in the study. The study group
      included all patients receiving aspirin during surgery, while the rest of the
      patients comprised the control group. Demographic data, surgery type and
      complication rate were collected. Complications were classified as major or minor
      hematoma, wound infection and dehiscence. Statistical significance was calculated
      using the Student's t-test and Chi test. RESULTS: During the study period 7259
      patients underwent minor cutaneous surgery (without local flaps or skin grafts).
      A group of 115 patients taking either Plavix (Clopidrogel) or Coumadin (Warfarin)
      were excluded. The study group consisted of 1088 patients who were taking aspirin
      regularly while 6056 patients comprised the control group. A statistically
      significant change was found between the two groups regarding sex, age,
      background chronic diseases and in the distribution of lesions across the body.
      No significant change was found regarding the peri-operative complications.
      CONCLUSIONS: In this large-scale prospective study, dermatologic surgery on
      patients receiving aspirin was found to be safe, as no statistically different
      complication rate was found between the study and the control groups. This
      statement is further emphasized due to the significantly statistically older age,
      chronic illness rate and the head and neck location of the lesions in the study
      group.

PMID- 20812495
TI  - [Parents compliance to perform the voiding cystourethrogram test after urinary
      tract infection].
AB  - Urinary tract infections (UTIs) occur in 3-5% of girls and 1% of boys. UTIs have
      been considered an important risk factor for the development of renal
      insufficiency, hypertension or end-stage renal disease. Hence, there is a need
      for early diagnosis and management of UTI to prevent renal scarring. The
      guidelines concerning the prophylactic treatment and the imaging studies have
      changed during the past year. It was believed that reflux predisposed to renal
      infection (pyelonephritis) by causing renal injury or scarring and that imaging
      studies in children with UTI were meant to identify anatomic abnormalities that
      predispose them to infection and renal scaring. Today, this concept is no longer
      prevalent and there is no recommendation to perform voiding cystourethrogram
      (VCUG] after every UTI. AIM: To examine parents' compliance to perform a VCUG
      test after hospitalization due to UTI and factors affecting their decision.
      METHODS: We performed a retrospective study that included all children who were
      hospitalized and diagnosed with UTI at "Dana" Children's Medical Center during
      the period 1/2004 - 12/2005. Hospital file records were collected, and the
      relevant data were obtained. We collected data regarding the parents' compliance
      to perform a VCUG according to a telephone interview. RESULTS: A total of 227
      children participated in the study; 179 (78.85%) parents agreed to partake in the
      interview. Overall, 52% of the children didn't perform the VCUG because of
      concern about exposure to radiation (55.91%), fear and distress from pain during
      the test (43.03%), fear of irreversible damage to the urinary tract (40.86%),
      lack of relevant information (35.48%] and the primary pediatrician's
      recommendation to postpone the test. The remaining 48% conducted the test because
      of the hospital doctor's recommendation (94.18%), Primary pediatrician
      recommendation (94.18%) and because of the desire to terminate prophylactic
      treatment (63.95%). There is a significant correlation between the doctors'
      recommendation and the extent and clarity of their explanation to the parents'
      understanding of the importance of the test, to the parents' satisfaction from
      the explanation and to the compliance to perform the test. CONCLUSIONS: There is
      a need to improve the doctors' explanation regarding the performance of VCUG test
      post UTI. This will improve the patients' compliance to perform their post
      discharge recommendation.

PMID- 20812496
TI  - [Strive, plan and reach the "Summit": the Faculty Development Program at the Ruth
      & Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology].
AB  - BACKGROUND: In recent years, faculty development has turned into a central
      component of medical education and a primary instrument in qualifying physicians
      to be teachers and educators. The faculty development program at the Ruth & Bruce
      Rappaport Faculty of Medicine ("Summit" program) was established in order to
      improve teaching of the clinical professions, to create a community of medical
      teachers and educators and to develop leadership in medical education within the
      Faculty of Medicine. OBJECTIVE: This article aims to describe the design,
      implementation and evaluation of the faculty development program in the
      Technion's Faculty of Medicine. METHODS: The program was designed for a group of
      20 clinical teachers, of various clinical professions, who had gained at least
      one year of undergraduate teaching experience and wished to develop a career in
      medical education. The program included seven monthly, eight-hour meetings
      throughout the academic year. Learning was based on small group discussions,
      interactive exercises, role-plays and simulations, self-directed reading and
      reflective writing. At the end of the final meeting, participants completed an
      evaluation form. RESULTS: Seventeen of the 20 participants (85%) graduated and
      received certificates. Learners' overall satisfaction was high. Graduates
      expressed high motivation to practice medical education within the Faculty of
      Medicine and reported that they gained new knowledge in medical education and
      skills regarding various aspects of teaching and learning, such as formulation of
      learning objectives, designing role plays, and providing effective feedback.
      CONCLUSIONS: The "Summit" program is an innovative initiative in the field of
      medical education in Israel. The program had a significant impact on
      participants' knowledge, teaching skills and attitudes. In order to ensure
      implementation of the acquired tools and skills, its shortterm and long-term
      effects on teaching behavior and the learning climate have yet to be
      demonstrated. In addition, it is necessary to check if the program affected the
      faculty as an organization, promoted changes in curricula, teaching and
      evaluation methods.

PMID- 20812497
TI  - [The national health status].
AB  - During the Golden Age of Medicine (20th Century), scientific and technological
      breakthroughs enabled physicians to treat diseases that were previously
      incurable. The idealist, romantic approach of medical practice believed in the
      right of every human being to receive the best treatment possible, regardless of
      cost. However, the rise in health care expenditure at the end of the last century
      made this approach impossible to follow. The growing health expenses are due to
      the increased percentage of chronically sick patients and elderly population,
      costs of novel technologies and public expectations. Israel spends 7.9% of its
      GDP on health, a figure which has not changed in the last fifteen years, while
      other western countries spend a considerably higher and increasing percentage of
      their GDP on health. Public resources must be allocated in order to maintain the
      health of the population and to decrease inequities. A data-based demonstration
      of the population health status and health care system is therefore mandated. in
      this issue of the Harefuah, three articles are presented which try to show
      different aspects of the measurement of Israeli heath status. The data
      accumulated is used to improve the health status of the Israeli people. The
      Israel Medical Association (IMA) has assumed responsibility for the creation of
      an objective index for the measurement and evaluation of the public state of
      health and the healthcare system. The goal of the IMA National Health Index is to
      promote discussions regarding medicine and health in Israel, and to serve as a
      tool to be used by relevant policy makers. Prof. Israeli et al discuss the merits
      of the National Health Index as well as delineate the difficulties regarding the
      methodology and choice of parameters. They suggest methods for its improvement.
      Dr Cohen and his colleagues of Clalit Health Services present the Quality Health
      indicator program in the community. In effect over the past fifteen years, this
      program is based on seventy evidence-based quality indicators and has brought
      real progress in several domains reflecting both teamwork as well as improvement
      of clinical quality. The question of inequity is a major problem in the Israeli
      health care system. According to one indicator, private out-of-pocket financing
      has reached 44% of the health care budget, more than other European countries.
      Maccabi Healthcare Services has implemented a multi-annual strategy to promote
      equity which is presented in this issue of Harefuah by Dr Wilf-Miron. Common to
      all these important papers is their emphasis on the measurement of health care
      indicators as a method for promoting better and more equally provided healthcare
      services to the Israeli population.

PMID- 20812498
TI  - [Eluding clinical medicine: a phenomenon that can be stopped].
AB  - A study published in this issue (Lotan et at.) reveals distressing data on the
      percentage of 4th year students, after their first clerkship, that regret their
      choice of medicine as a career and contemplate a non-clinical vocational path.
      This phenomenon, entitled "eluding clinical medicine", is analyzed in terms of
      early professional socialization of the students toward sciences and their
      difficulty to tolerate ambiguity and uncertainty, so typical to clinical
      medicine. Also discussed is the student's incapability to integrate acquired
      knowledge across disciplines and to interweave it into clinical reality.
      Rectification of this escape from clinical medicine" may require modification of
      the pattern of the students' professional socialization during their first years
      of studies by such measures as early clinical exposure, interdisciplinary
      integration and practice in decision-making and problem-solving throughout the so
      called "preclinical phase". The alarming findings presented in the above
      mentioned study call for immediate response.

PMID- 20812499
TI  - [The use of anti-angiogenic drugs for central retinal vein occlusion].
AB  - Central retinal vein occlusion (CRVO) is one of the common causes of visual loss.
      The main reasons for decreased vision are development of macular edema, macular
      ischemia and neovascular glaucoma. The introduction of anti-vascular endothelial
      growth factor (VEGF) drugs for CRVO in 2005 demonstrated marked improvement in
      visual acuity, macular edema and ocular neovascularization. However, the absence
      of clear guidelines for the treatment of CRVO presents a genuine therapeutic
      challenge. In a national study conducted among the Israeli society of retinal
      specialists (personal communication), it was found that most of these specialists
      would recommend intravitreal anti-VEGF drug injection immediately upon the
      diagnosis of macular edema in non-ischemic CRVO with visual acuity of 6/15 or
      less. Only 21% would recommend this treatment in ischemic CRVO with visual acuity
      of 6/60 or less, if no macular edema exists. After the edema resolves, 94% would
      follow-up the patients by imaging with optical coherent tomography every 4-6
      weeks, and recommend further treatment accordingly. Large prospective controlled
      studies are warranted in order to address the important issues of when to start
      anti-VEGF treatment for CRVO, when to withhold treatment, and recommended
      treatment intervals.

PMID- 20812500
TI  - [Treatment modalities in central retinal vein occlusion].
AB  - Central retinal vein occlusion (CRVO) remains one of the most common retinal
      vascular disorders that may lead to blindness. The etiology is unknown, however,
      predisposing factors such as hypertension, diabetes, atherosclerosis and
      hypercoagulable states have all been described. Local ophthalmic illnesses such
      as open angle glaucoma, ocular trauma and orbital infections have also been
      suggested as causative. CRVO can be subdivided into two clinical types, ischemic
      and non-ischemic. The non-ischemic type comprises the milder form of the disease
      with partial venous obstruction and good visual outcome. Ischemic CRVO is the
      severe form and is associated with visual loss, because of nearly total retinal
      vein obstruction and poor perfusion to retina. In addition, patients with
      ischemic CRVO may end up with additional complications such as neovascular
      glaucoma that may lead to blindness. Over 90% of CRVO occurs in patients > 65
      years. The presenting symptom is a sudden painless mono-ocular decrease in visual
      acuity which could result from macular edema, ischemia, or intraocular bleeding.
      Ophthalmoscopic examination reveals macular edema, retinal bleeding (more
      peripheral), tortuous vein dilatation and swollen disc. Current treatment
      modalities include systemic use of anticoagulation drugs, local treatments
      including laser, intravitreal injection of anti-vascular endothelial growth
      factor and surgery (vitrectomy). This review presents the current therapeutic
      modalities in CRVO.

PMID- 20812501
TI  - [Childhood vaccines and autism--much ado about nothing?].
AB  - The increased diagnoses of autism and developmental disorders in recent decades,
      together with the childhood vaccination program, has led to the hypothesis that
      vaccination in general, and the measles, mumps, and rubella virus live vaccine,
      and vaccines that contain mercury, in particular, cause autism. It has been
      hypothesized that intestinal infection caused by live virus vaccines change the
      permeability of the intestinal wall, and subsequently, the passage of peptides
      through the intestinal wall to the blood, and from there to the brain. It has
      been suggested that the accumulation of these peptides in the central nervous
      system causes autism. Studies that investigated this theory did not find an
      association between vaccine administration and between digestive system symptoms
      and autism. According to a second hypothesis, an organomercury compound
      (Thimerosal), used as a preservative in vaccines that do not include live
      viruses, is a cause of autism. Like the former, this hypothesis has been well
      researched, and refuted. Some studies have in fact found an increase in autism
      diagnosis among children who were vaccinated after Thimerosal was removed from
      the vaccine preparation. Recent studies have refuted the theory that the
      consecutive administration of vaccines weakens the young immune system in
      children, and leads to an autoimmune process that causes autism. The etiology of
      autism is still unknown, with research continuing from different directions. The
      extensive research conducted so far indicates that childhood vaccination is not a
      cause of the sharp increase in autism diagnoses in recent decades.

PMID- 20812502
TI  - [256 scientific ties between Jews and Germans, Israel and Germany from the 20th
      century until today Conference held in Jerusalem on November 17th 2008].

PMID- 20812503
TI  - [Taxonomic position of certain representatives of sulphate-reducing corrosive
      microbial community].
AB  - Sulfate-reducing bacteria and their heterotrophic satellites have been isolated
      from the biofilm formed on steel by sulfidogenic corrosive microbial community.
      Bacteria were characterized according to phenotypical features and investigated
      by the methods of molecular-genetic analysis. In accordance with the phenotypical
      features the studied strain of sulfate-reducing bacteria were related to
      Desulfovibrio genus, Gram-positive strains of heterotrophic satellites were
      related to Bacillus genus, B. firmus and B. subtilis species. Gram-negative
      strains, as to their physiological-biochemical characteristics were related to
      Pseudomonas genus, P. aeruginosa species, Stenotrophomonas genus, S. maltophilia
      species, and Aeromonas genus, A. hydrophila/caviae species. Taxonomic position of
      certain representatives of the community is confirmed by the molecular-genetic
      methods. A comparative analysis of the sequencing results has evidenced for the
      identity of sequences of 16S rRNA of the studied bacteria with analogous sequence
      of strains from the GenBank database. Nucleotide sequence of strain 27 has a 99%
      homology with the sequence of Pseudomonas aeruginosa, strain 36 deposited at
      GenBank to nucleotide sequence of Bacillus subtilis. As to sulfate-reducing
      bacteria, only their belonging to Desulfovibrio genus has been confirmed. Thus
      the results of sequence-analysis of 16S rRNA genes are in agreement with the data
      obtained from studying the phenotypical features.

PMID- 20812504
TI  - [Physiological properties and taxonomic position of soil microorganisms
      destructors of hexachlorcyclohexane].
AB  - Eleven (11) microbial strains capable to decompose insecticide
      hexachlorcyclohexane (HCH) have been isolated from microbial association
      resistant to chloro-organic pesticides. On the basis of investigation of
      morphological, cultural, physiological, biochemical characteristics and results
      of sequence of gene 16S rRNA it has been established, that the best strain
      destructors N 3 and N 9 belong to Pseudomonas putida species, and strain N 6
      belongs to Stenotrophomonas maltophilia species.

PMID- 20812505
TI  - [Destruction of motor oils by actinobacteria].
AB  - The influence of high concentrations of motor oils (MO) and additives to them on
      the growth of strains Dietzia maris UKM Ac-205, Gordonia rubripertincta UKM Ac
      179 and Rhodococcus erythropolis UKM Ac-50 as well as the ability of these
      actinobacteria to destruction of different MO brands were investigated. It was
      shown that all strains were resistant to the used motor oils but showed
      sensitivity to fresh (unused) MO and additives containing zinc dithiophosphate.
      The oil "Esso Ultra" which had minimum inhibitory concentration (MIC) within 200
      400 mg/ml and the antiwear additive Multadit OB (MIC = 4-10 mg/ml) were most
      toxic for actinobacteria. It is established that the level of MO degradation at
      initial concentration of 10 g/l was 25.5-56.0% for 5 days. The studied strains
      utilized paraffine-naphthene (49.0-61.0%) better than aromatic (18.1-22.5%) and
      resinous-asphaltene (12.1-18.8%) fractions of motor oils.

PMID- 20812506
TI  - [Metabolism peculiarities of bacteria restoring chlorates and perchlorates].
AB  - Bacteria facultative anaerobes capable to restore chlorine oxygen compounds -
      chlorates and perchlorates, using them as terminal acceptors of electrons, have
      been isolated from various natural sources. Chloride is the end product of this
      process. Besides chlorates and perchlorates the isolated bacteria also restored
      other electron acceptors: chromates, sulfates, nitrates, vanadates, manganates.
      The studied restored bacteria use awhole number of organic compounds as electron
      donors. The paper is presented in Russian.

PMID- 20812507
TI  - [Structural components and peculiarities of Pseudomonas aeruginosa biofilm
      organization].
AB  - Peculiarities of the structural organization of bacterial biofilm during its
      formation and disintegration have been investigated on the model of Pseudomonas
      aeruginosa UCM B-900 (ATCC 9027). It was shown, that development of the biofilm
      in a stationary system on glass was a two-vector process with changes in time and
      space. P. aeruginosa UCM B-900 biofilm is formed from single cells, passes
      through the stages of base components, net structure, islands and comes to the
      end with integration into a complete monolayer. The biofilm degradation repeats
      the stages of its formation in the reverse sequence.

PMID- 20812508
TI  - [Influence of silicon dioxide and saponite on growth of Bacillus subtilis IMV B
      7023].
AB  - Growth of Bacillus subtilis IMV B-7023 was studied under the presence of silicon
      dioxide and saponite cultivation in the medium. It was established that the
      adding ofthese materials into the medium affects significantly the bacteria
      growth activity. Efficiency and orientation of the process depends on the type of
      dispersed material and contents of phosphate in the cultivation medium. Thus,
      under the concentration of 0.6 g/l PO4(3-) saponite stimulates the growth of
      bacteria but at a lower concentration (0.1 g/l PO4(3-)) growth activity of
      microorganisms becomes lower. At the same time in the presence of silicon dioxide
      the stimulation of bacterial growth is observed at different concentrations of
      phosphate in the medium. It is shown that the present effect is not the result of
      the phosphate sorption on the surface of the investigated dispersed materials.
      The contact interaction of solid particles with bacterial cells was found.

PMID- 20812509
TI  - [Absence of mutagenic effect of Pseudomonas syringae pv. atrofaciens 9400 and
      Pantoea agglomerans P324 culture liquids].
AB  - The mutagenic activity of the culture liquids of phytopathogenic strain
      Pseudomonas syringae pv. atrofaciens 9400 and epiphytic strain Pantoea
      agglomerans P324 was studied in the Ames test and Allium cepa-test. In pro- and
      eucariotic test-systems no effect of the culture liquids of these bacteria on
      spontaneous mutations of Salmonella typhimurium TA98 and TA100 or chromosome
      aberrations in the cells of Allium cepa root apical meristem was found.

PMID- 20812510
TI  - [Effect of amyxine, loramyxine and their composites with yeast RNA on spontaneous
      and induced mutagenesis in Salmonella typhymurium].
AB  - It was found out that amyxine, loramyxine and their composites with yeast DNA do
      not increase reliably the frequency of spontaneous mutations in test-strain S.
      typhymurium TA 98. The studied substances do not possess the antimutagen activity
      in respect of mutations, induced by potassium bichromate in S. typhymurium TA 98
      and do not increase their quantity.

PMID- 20812511
TI  - [Using the laboratory strains of Escherichia coli for studying colicinogenicity].
AB  - The indicator system which includes laboratory strains of Escherichia coli K12,
      K12-C600, BE, and C-Ia is offered for studying colicinogenicity. It has helped to
      establish that 32 of 100 patients with dysbacterioses of colon carry a colicin
      producing strain of E. coli. A tendency is discovered to the increase of
      occurrence of colicinogenic strains of escherichias with patients' age. Only 24%
      of E. coli strains form active colicins in a group of one-year old children.
      Frequency of colicinogenic strains occurrence increases to 33 and 42 %,
      respectively, in teenagers and adult patients. A strict decrease of total
      activity of colicins is the main peculiarity of polymicrobe associations in which
      the prevailing strain of E. coli is accompanied by 3-5 strains of other
      enterobacteria. As to their sensitivity of colicins the indicator strains are
      arranged in the following order: K12-C600 (84%), KR (69%), BE (63%) and C-Ia
      (47%). In spite of that, the low-sensitive strains can be effective for
      identification of very specific colicins. Since the laboratory strains of E. coli
      K12, BE and C-Ia are the hosts for specific bacteriophages of E. coli, the
      indicator system on their basis may be useful for studying the interrelation
      between colicins and coliphages, as well as plasmids and restriction-modification
      systems. The paper is presented in Russian.

PMID- 20812512
TI  - [Proteolytic enzymes of microorganisms].
AB  - Microbial proteolytic enzymes are able to hydrolyze various protein substrates.
      Data concerning the ability to degrade proteins amongst various groups of
      microorganisms, such as bacteria, fungi, actinomycetes and yeasts, are collected
      in this article. The physical and chemical properties of proteolytic enzyme
      preparations and methods of their separation and purification have been examined.
      The possible ways of these enzymes application in industry and medicine have been
      discussed. The paper is presented in Ukrainian.

PMID- 20812513
TI  - Childhood pneumococcal vaccination in Europe.

PMID- 20812514
TI  - Measles vaccination.

PMID- 20812515
TI  - Reducing the risk of pertussis in newborn infants.

PMID- 20812516
TI  - Sunlight (actinic) keratosis: an update.

PMID- 20812517
TI  - Role of congenital rubella reference laboratory: 21-months-surveillance in
      Liguria, Italy.
AB  - INTRODUCTION: Rubella is generally a mild rush fever disease when acquired in
      childhood, but when infection occurs during the first months of pregnancy, high
      risk of trans-placental transmission to the foetus and of congenital anomalies
      exists. In November 2003, a National Plan for measles and congenital rubella
      elimination was approved in Italy. The aim was to reduce and maintain Congenital
      Rubella Syndrome incidence lower than 1 case per 100,000 live births/year by
      2007. Since June 2006, Liguria Administrative Region recognized U.O. Hygiene,
      "San Martino" University Hospital, Genoa, as regional reference laboratory for
      diagnosis of rubella infection during pregnancy and post-partum. METHODS: Twenty
      one-month virological-surveillance results between April 2007 and December 2008
      were reported in terms of demographic data, risk factors, access reasons,
      clinical picture, vaccination, previous rubella disease, laboratory results of
      pregnant women and newborns. RESULTS AND CONCLUSION: Since the beginning of
      surveillance, 65 pregnant women with suspected virus infection and 18 newborns
      with suspected congenital rubella were followed up. The results of laboratory
      surveillance highlighted (i) the importance of an early screening, (ii) the
      suboptimal specificity of chemiluminescent assays, that often yield false
      positive IgM results and (iii) the fundamental role of second-level laboratory to
      confirm the serological diagnosis and to detect the virus by molecular
      techniques.

PMID- 20812518
TI  - Evidence of hepatitis E virus (HEV) infection in human and pigs in Sardinia,
      Italy.
AB  - INTRODUCTION: The aim of this study was to determine the seroprevalence of anti
      HEV antibodies in humans sera and to study HEV prevalence in swine from different
      Sardinian farms, testing viral HEV-RNA in bile samples. METHODS: In the first six
      months of 2008, 532 subjects of whom 402 blood donors and 130 workers at zoonotic
      risk, were enrolled. Anti-HEV were determined with an enzyme linked immunosorbent
      assay (ELISA). In positive subjects, RNA was extracted and tested by RT-Nested
      PCR. From July 2006 to March 2007, 95 bile samples were collected from randomly
      selected pigs. RNA was extracted from 250 microl of bile and tested by RT-Nested
      PCR. RESULTS: The overall prevalence of anti-HEV antibodies was 4.3%; 5.0% among
      blood donors and 2.3% among workers at zoonotic risk, with no statistically
      significant differences between sex, age classes and occupation. The search for
      HEV-RNA in the subjects positive for antibodies, gave negative results. HEV
      genome was detected in 6 of the 95 swine bile samples tested. Sequences were
      clustered within the genotype 3 and are edited on GenBank under accession number:
      from FJ850960 to FJ850962 and from FJ883000 to FJ883002. DISCUSSION: The overall
      prevalence of anti-HEV shows that the virus circulates without giving origin to
      cases of acute hepatitis. The low prevalence value found in workers at zoonotic
      risk do not apparently support the hypothesis of professional risk. In this
      study, HEV-RNA was isolated from pigs in Sardinia for the first time confirming
      the role of swine as HEV reservoir and the possibility of virus transmission to
      humans.

PMID- 20812519
TI  - Persistent oral and urinary Candida spp. carriage in Italian HIV-seropositive
      asymptomatic subjects.
AB  - The aim of the present study was to ascertain frequency and persistence of
      Candida spp. oral and urinary carriage in asymptomatic, HAART-naive HIV
      seropositive subjects who had not undergone therapy with antimycotic drugs, and
      whose CD4+ lymphocyte count was greater than 200/microl. Oral carriage was the
      most common Candida spp. carriage (63.0% of the subjects), while candiduria was
      more rarely observed (6.5%). C. albicans was recovered from the majority of the
      subjects examined (56.5%), followed by C. krusey (4.3%), C. tropicalis (2.2%) and
      C. dubliniensis (2.2%). C. albicans was also isolated from two urinary carriers
      (4.3%) and C. glabrata from another one (2.2%). The same C. albicans clone was
      repeatedly isolated from 14 out of 15 oral carriers while the same clone of C.
      dubliniensis was repeatedly isolated from one carrier, as shown by the
      persistence of RAPD fingerprint of serial isolates during one year of follow-up.
      Since persistence of Candida spp. carriage may influence the development of
      clinical candidiasis in immunocompromised hosts, monitoring of the carrier status
      could be useful for preventing clinical thrush in HIV-seropositive subjects.

PMID- 20812520
TI  - Eliminating congenital rubella: a seroepidemiological study on women of
      childbearing age and MMR vaccine coverage in newborns.
AB  - INTRODUCTION: Rubella can have particularly serious effects on the product of
      conception if contracted during pregnancy. Thus, the main aim of rubella
      vaccination programmes is to prevent infection during pregnancy. MATERIALS AND
      METHODS: A seroepidemiological study was conducted from July 2006 to December
      2007 on 1000 women of childbearing age, 15 to 45 years old, using specific
      rubivirus antibody assays, IgG and IgM. A questionnaire administered at the same
      time allowed us to survey how much women knew about this disease. In addition,
      MMR vaccine coverage rates were analysed for cohorts born in the local health
      districts of Messina for the period 1993-2006. RESULTS: An analysis of the
      replies given to the questionnaire showed an estimated 42.8% of the women to have
      immunity from rubella, while the serological study showed an immunity coverage
      rate of80.6%. Vaccination coverage in the local health districts regarding the
      first dose of MMR was 81% (cohorts 1993-2005), while the rate was only 24% for
      the second dose (cohorts 1993-2002). CONCLUSIONS: Both immunity coverage in women
      of childbearing age and that for newborns (for the cohort considered)fall below
      the 95% target set by the National Elimination Plan for Measles and Congenital
      Rubella (PNEM). It is therefore necessary to provide women with adequate
      information about the risks of rubella during pregnancy and about the benefits of
      vaccination, as well as to recoup subjects at risk or those whose immune status
      is unknown. Public health authorities also need to make continued efforts to
      increase the number of MMR vaccinations throughout the region.

PMID- 20812521
TI  - Attitude towards and use of ecstasy in medical university interns' based on HBM.
AB  - Using a self-reported questionnaire, 130 Yazd Medical University students were
      surveyed about their knowledge towards ecstasy and their use of ecstasy based on
      Health Belief Model. The age range was 18-31 years. Approximately, 23% of
      students had seen an ecstasy tablet, 6 (4.6%) had used ecstasy (2 female and 4
      male), 4 of them lived in a dormitory and 2 were tenants. The levels of
      knowledge, perceived barrier and perceived benefit of students who had used
      ecstasy were lower than those who hadn't used ecstasy. There was a significant
      difference between the knowledge, perceived barrier and perceived benefit of
      samples and use of ecstasy (p < 0.008, p < 0.003 and p < 0.13, respectively).
      Approximately, 74% of the students were eager to know more about ecstasy and its
      effects. Finally, the students were asked to select one or more item from a list
      of six which they considered the best way for providing young people with
      accurate information, and the responses (as percentages) for each source were as
      follows: discussion with parents: 1.5%; television programs: 64.6%; radio
      programs: 1.5%; talk at university: 12.3%; friends: 12.3%; newspapers/magazine
      articles: 7.7%. The data revealed that the knowledge of participants about
      ecstasy was low (mean = 27.69 +/- 3.53 out of 48). The mean grade score of
      knowledge of males was more than females. A survey in Kerman (Iran) showed that
      the knowledge of general practitioners about ecstasy was lower than 50% and the
      knowledge of males was more than females.

PMID- 20812522
TI  - Interview with William C. Schoenhard, FACHE, deputy under secretary for health
      for operations and management, U.S. Department of Veterans Affairs. Interview by
      Stephen J. O'Connor.

PMID- 20812523
TI  - ARRA and meaningful use: is your organization ready?

PMID- 20812524
TI  - Unionization in healthcare strategies.

PMID- 20812525
TI  - A lack of standardization: the basis for the ethical issues surrounding quality
      and performance reports.
AB  - Consumers in the United States are taking advantage of the proliferation of
      publicly available, internet-based performance reports and quality appraisals of
      health plans, healthcare organizations, hospitals, and physicians to aid in their
      healthcare decision making. However, these appraisal practices have given rise to
      controversy and debate over certain distinctive ethical issues. This article
      advocates a standardized ethical framework to guide current and future
      development and implementation of performance reports. This framework, which
      would resolve a number of the major issues, includes the following ethical
      principles to guide the practice of public reporting on the Internet and
      facilitate enhanced quality improvement in the healthcare industry: legitimacy,
      data integrity and quality, transparency, informed understanding, equity, privacy
      and confidentiality, collaboration, accountability, and evaluation and continuous
      improvement.

PMID- 20812526
TI  - Hospital readmissions under the spotlight.
AB  - Healthcare leaders see the future of their dynamic industry through the eyes of
      patients, families, providers, clinicians, employers, health insurers, and
      policymakers. As healthcare organizations face growing economic challenges and
      the nation engages in comprehensive healthcare reform, reducing preventable
      readmissions is considered part of the solution to achieving new system-wide
      efficiencies. Healthcare leaders can adopt a fresh approach to reducing
      preventable readmissions that includes three basic components: (1) identify
      patients at risk for readmission based on sociodemographic factors, care-related
      factors, and measures of severity of illness; (2) anticipate reform that aligns
      reimbursements and payment incentives for readmission reductions; and (3)
      structure coordinated, patient-centered discharge planning. Three innovative
      programs can be used to coordinate care at discharge: the Society of Hospital
      Medicine's Better Outcomes for Older Adults Through Safe Transitions project;
      Boston University Medical Center's Reengineered Hospital Discharge project; and
      the Institute for Healthcare Improvement's STate Action on Avoidable
      Rehospitalizations initiative. This three-pronged approach will help
      organizations proactively create mechanisms that are aligned with the national
      agenda and that keep people healthy at home after hospital discharge.

PMID- 20812527
TI  - Quantifying the economic impact of communication inefficiencies in U.S.
      hospitals.
AB  - Care delivery is a complex enterprise that involves multiple interactions among
      multiple stakeholders. Effective communication between these dispersed parties is
      critical to ensuring quality and safety and improves operational efficiencies.
      Time and motion studies in hospital settings provide strong evidence that care
      providers-doctors and nurses-spend a significant proportion of their time
      obtaining or providing information (i.e., communicating). Yet, surprisingly, no
      studies attempt to quantify the economic waste associated with communication
      inefficiencies in hospital settings at a national level. Our research focuses on
      developing models for quantifying the economic burden on hospitals of poor
      communications. We developed a conceptual model of the effects of poor
      communications in hospitals that isolates four outcomes: (1) efficiency of
      resource utilization, (2) effectiveness of core operations, (3) quality of work
      life, and (4) service quality, identifying specific metrics for each outcome. We
      developed estimates of costs associated with wasted physician time, wasted nurse
      time, and increase in length of stay caused by communication inefficiencies
      across all U.S. hospitals, using primary data collected from interviews in seven
      hospitals and secondary data from a literature review, the Bureau of Labor
      Statistics (BLS), and the Agency for Healthcare Research and Quality (AHRQ). We
      find that U.S. hospitals waste over $12 billion annually as a result of
      communication inefficiency among care providers. Increase in length of stay
      accounts for 53 percent of the annual economic burden. A 500-bed hospital loses
      over $4 million annually as a result of communication inefficiencies. We note
      that our estimates are conservative as they do not include all dimensions of
      economic waste arising from poor communications. The economic burden of
      communication inefficiency in U.S. hospitals is substantial. Information
      technologies and process redesign may help alleviate some of this burden.

PMID- 20812528
TI  - Healthcare reform and the hospital industry: what can we expect?
AB  - Healthcare costs continue to increase dramatically, while quality remains a
      significant problem. Reform measures adopted by Congress will fuel expansion of
      these costs, further stressing taxpayers and employers and forcing hospitals to
      adopt transformational changes as they adjust to increased demands for services
      and shrinking reimbursement. Cost control and quality improvement can be achieved
      through increased competition or greater government intervention. Competition
      will require unpalatable changes to the healthcare system to decrease costs
      without further restricting access or decreasing quality. Increased government
      intervention will result in changes to reimbursement and hospital-physician
      relations and increased demands for improved care. To improve cost and quality
      while preserving increased access, we advocate for a universal standard coverage
      of Americans; accountable healthcare system leadership; leverage of information
      resources to make utilization decisions and evaluate performance; alignment of
      physician, hospital, and payer incentives to focus on care outcomes rather than
      profit maximization; and the use of quasicompetition to allow for consumer choice
      within this system.

PMID- 20812529
TI  - Critical issues in chronic prostatitis.
AB  - In the last decade, an impressive amount of clinical research data has shed new
      light on pathogenesis and management of the chronic prostatitis syndrome. A new
      classification and a validated symptom score have enabled urologists worldwide to
      speak a "common language", thus greatly improving the amount and quality of
      focused research in this field. In Europe, a large number of groups and experts
      have been actively involved in this research, and have developed in many cases a
      genuine view on prostatitis and chronic pelvic pain etiology, diagnosis and
      treatment. The present paper, written by a panel of researchers from Europe and
      Far East Russia, reviews the most recent findings, discusses the most
      controversial contemporary topics on prostatitis syndromes, and highlights a
      number of unresolved issues requiring further research and study.

PMID- 20812530
TI  - Paediatric urolithiasis in central coast region of Tunisia: clinical
      characteristics.
AB  - OBJECTIVE: To show an outline of the clinical and biological characteristics of
      paediatric urolithiasis among Tunisian children in the coast region. PATIENTS AND
      METHODS: This retrospective study included 168 children under the age of 16 years
      presented with urinary stones (100 boys and 68 girls). Patients were reviewed in
      a multi-centric study with regard to age at diagnosis, sex, history, and
      physical, laboratory, and radiologic findings. The physical and chemical analysis
      of stones was carried out respectively by a stereomicroscope and by infra-red
      spectroscopy. RESULTS: The sex ratio was 1.47. The clinical presentation of this
      pathology was dominated by abdominal pain (28%), hematuria (25.6%), dysuria
      (16.7%) and urinary tract infection (14.3%). Stones were located in the upper
      urinary tract in 75.6% of cases. Of the urine cultures, 14.3% were positive.
      Whewellite was more frequent in children stones than in infants (p < 0.05) and
      was the main component in 46.4% of stone section and 55.4% in stone surface.
      CONCLUSION: The male prevalence of paediatric urolithiasis is progressively
      decreasing in Tunisia. The epidemiological profile of renal stones in our country
      has changed towards a predominance of calcium oxalate stone and upper tract
      location.

PMID- 20812531
TI  - Pyrrolidine dithiocarbamate treatment prevents ethylene glycol-induced
      urolithiasis through inhibition of NF-kappaB and p38-MAPK signaling pathways in
      rat kidney.
AB  - The aim of this study was to evaluate the role of the inducible nitric oxide
      synthase (iNOS), selective nuclear factor-kappaB (NF-kappaB) and p38-mitogene
      activated protein kinase (p38-MAPK) on oxalate-induced crystal deposition in
      renal tubules. The rats were divided into three groups; group 1; control group,
      group 2; ethylene glycol (EG) group, group 3; EG + pyrrolidine dithiocarbamate
      (PDTC) group. Rats were sacrified on 7, 15 and 45th days. The iNOS expression,
      p65/NF-kappaB and p38/MAPK activity, and oxidative stress markers were evaluated
      in the kidney. Crystal depositions were evident on day 7, mild and severe
      crystallization were observed on day 15 and 45 in EG group, respectively. There
      was limited or no crystal formation in the EG + PDTC group. While EG stimulates
      iNOS, p65/NF-kappaB and p38/MAPK activity in renal tubules, PDTC inhibited it.
      PDTC prevents crystal depositions in renal tubules by reducing oxidative stress,
      iNOS, NF-kappaB, and p38-MAPK expression.

PMID- 20812532
TI  - Prostate cancer detection after one or more negative extended needle biopsy:
      results of a multicenter case-findings protocol.
AB  - OBJECTIVES: To evaluate PCa incidence in patients with one or more negative
      extended prostate biopsy who underwent repeat biopsy or TURP. MATERIAL AND
      METHODS: From June 2003 to February 2008, 308 patients were submitted to repeat
      prostate biopsy (median 20.5 cores) and 120 patients underwent TURP after one or
      more 12 cores prostate biopsy. Indications for biopsy were: abnormal DRE; PSA >
      10 ng/mL; PSA included between 4.1-10 or 2.6-4 ng/mL with free/total PSA < or =
      25% and < or = 20%, respectively 262 and 46 underwent a second and a third
      biopsy: 218 because for high levels of PSA, 40 and 50 patients for a previous
      diagnosis of HGPIN and ASAP, 28 had an abnormal DRE. PSA in patients who
      underwent TURP was 11.6 ng/mL (median); in all cases DRE was negative and only 76
      patients referred LUTS. RESULTS: PCa incidence at repeat biopsy was 16.9%; 96.2%
      of cancers were diagnosed at a second biopsy and 3.8% at a third one. PCa
      incidence was higher in patients with previous ASAP (43.4% and 50%) vs patients
      with HGPIN (25% and 0%) or benign pathology (11.9% and 0%). PCa was diagnosed in
      11.1% and 19% of patients who underwent TURP previously submitted to a first and
      a second biopsy, respectively. CONCLUSIONS: In case of persistent suspicion of
      PCa after a repeated negative saturation biopsy, TURP should be proposed as part
      of the diagnostic procedure aside from LUTS, especially in patients with a life
      expectancy greater than 10 years.

PMID- 20812533
TI  - Is it possible to predict post-residual voided urine by bladder scan before
      uroflowmetry--a useful and timesaving test to reduce the number of non--evaluable
      uroflow measurements?
AB  - OBJECTIVES: Bladder-scan before uroflowmetry is useful to reduce non-evaluable
      Q(max)-data. A significant problem is to receive an adequate voided volume in
      uroflow-measurements. Aims of this study were 1--to confirm if pre-voiding
      bladder scan can reduce the number of inadequate flow measurements, 2--to
      establish threshold values for prevoiding bladderscan volumes before and after
      different treatments options 3--to study if it is possible to predict the post
      residual voided volume. MATERIAL AND METHODS: 121 patients performed 2
      uroflowmetry before and after different treatments. Bladder volume was measured
      by transabdominal ultrasound when the patient had the sensation to void and after
      uroflowmetry to calculate residual urine. Same investigations were repeated after
      different treatments. RESULTS: 21% of the patients had insufficient voided volume
      < 125 ml in 1st recording and 22% in 2nd; while 28% of the patient had a volume
      voided < 150 ml in 1st recording and 33% in 2nd. There was a strong correlation
      between the pre-voiding measured volume and the voided volume (r = 0.801, p <
      0.0001), linear regression analysis yielded 1st flow rate recording is Void-Vol =
      32.703 + (0.637 * Pre-Vol) and 2nd flow rate recording is Void-Vol = 16.264 +
      (0.704 * Pre-Vol) (r = 0.855; p < 0.0001). CONCLUSIONS: Bladder scanning before
      uroflowmetry reduces the number of non-evaluable Q(max) data. If a voided volumes
      of > 125 ml (> 150 ml) is required a mandatory pre-voiding bladder scan volume
      should be > 200 ml (> 250 ml), so non elegible Q(max) recordings will decrease
      from 21% to 5.8% (28% to 4.1%) in BPH patients who will undergo treatment and
      from 22% to 7.4% (33% to 5.8%) in BPH-treated patients. There is a difference
      between patients before and after treatment. It is not possible to predict the
      post residual voided volume by the bladder scan using the virtual calculation.

PMID- 20812534
TI  - Sarcoma of prostate: case report and review of the literature.
AB  - OBJECTIVES: Prostate sarcomas are rare entity, the most common is leiomyosarcoma
      which account for 0.1% of all prostate malignancies. The presenting symptoms are
      mainly obstructive urinary symptoms. Surgery with chemo- or radiotherapy are the
      mainstay treatment options. The overall survival rate remains poor regardless of
      initial tumour size, grade or histological subtype. Immunohistochemistry reveals
      tumour cells diffusely positive for vimentin, smooth muscle actin, focally
      positive for progesterone receptor, whilst keratins are usually negative.
      MATERIALS AND METHODS: We describe a case of a patient affected by sarcoma of
      prostate. Furthermore, we reviewed the cases of prostate sarcomas available in
      literature to clarify the best therapeutic options to be applied. RESULTS: In the
      case described leiomyosarcoma diagnosed by an ultrasound guided biopsy was
      characterized by fascicles of spindle-shaped cells with a variable degree of
      nuclear atypia. The immunohistochemistry showed positive staining for smooth
      muscle actin, vimentin and focally for the S-100 protein. The patient was treated
      with radical retropubic prostatectomy and radiotherapy of the local recurrence,
      and chemotherapy at metastases onset. CONCLUSIONS: Prostate sarcomas are highly
      aggressive, with limited therapeutic options. An early diagnosis and complete
      surgical excision with negative margins offer patients the long-term disease free
      survival.

PMID- 20812535
TI  - Laparoscopic versus open radical retropubic prostatectomy: a case-control study
      at a single institution.
AB  - We retrospectively compared 50 patients treated with open retropubic
      prostatectomy (RRP) with 50 patients treated with laparoscopic extraperitoneal
      radical prostatectomy (LRP) at our institution, in the same time period, with a
      follow-up up to 7 years. We focused on operative data, complications,
      pathological outcome and mid-term outcome and follow-up in terms of oncological
      results. The same surgeons performed both operations. The 2 groups were similar
      with respect to mean patient age, mean prostate specific antigen value, median
      Gleason score. No previous transurethral resection of the prostate nor
      neoadjuvant treatment, had been undertaken in both groups of pts. Mean operating
      time was significantly shorter after open surgery (126 minutes, range 90-185
      minutes) [p = 0.03] compared to the laparoscopic group (188 minutes, range 130
      250) but it did not differ significantly from the last 20 laparoscopic
      procedures, in which the time of procedure was reduced to a mean of 155 minutes
      group (range 140-184 minutes) [p = 0.1]. Mean blood loss (1,150 versus 800 cc)
      and transfusion rates (55.7% versus 19.6%) in the 2 groups significantly favored
      the laparoscopic group. Number of lymphnodes dissected during the procedures
      favoured, but not significantly, the RRP group: for RRP a mean 11 lymphnodes
      right side, 13 left side (ranges 2-20 and 2-19 respectively), while for LRP a
      mean of 9 lymphnodes right side, 11 left side (ranges 2-15 and 2-13 respectively)
      were collected. The complication rate was almost the same in both groups, with no
      major adverse events nor deaths, (19.2% versus 14.7%) but the spectrum differed.
      The laparoscopic group had a higher incidence of fever (1.8% versus 3.2%
      respectively) and subcutaneous or scrotal emphysema, whereas more lymphoceles
      (6.9% versus 0%), wound infection (2.3% versus 0.5%), embolism/pneumonia (2.3%
      versus 0.5%) and anastomotic strictures (15.9% versus 4%) occurred after open
      surgery. Median catheter time was longer after open retropubic prostatectomy (22
      versus 8.9 days, respectively) but the continence rates (intended as complete
      continence with no use of pads) were similar in both groups at 12 months (90.3%
      versus 91.7%). The rate of positive margins did not differ significantly in
      groups, and was in all cases very low (8.2% versus 7.0%), prostate specific
      antigen biochemical recurrence was equivalent (10% vs 10%). Data regarding
      postoperative sexual function favoured the laparoscopic group, even if no
      statistical significance was recorded (55% vs 67%). No statistical differences
      were observed in terms of oncological results, with a 24 months mean follow-up.
      Laparoscopic radical prostatectomy is technically demanding, with an initially
      longer operative time and learning curve. The overall outcome in our series
      favours the laparoscopic approach regarding catheterization time, recover of
      continence and impotence, hospital stay, transfusion rate. The open approach is
      favoured for the still shorter time necessitating for the procedure.
      Consequently, at our institution laparoscopic radical prostatectomy is becoming
      the method of choice.

PMID- 20812536
TI  - Ureteral injury concomitant with kidney injury due to blunt trauma: case report.
AB  - A 27- year old man fell from seven meters high. A CT of abdomen and pelvis with
      contrast injection showed injury of right kidney, perirenal hematoma, and
      periureteral extravasation of contrast. Retrograde pyelography confirmed the
      diagnosis of partial transection of the right upper ureter. Conservative
      management of the case is discussed. A JJ internal ureteral stent was inserted
      successfully.

PMID- 20812537
TI  - Thirty years old man with a huge benign prostatic enlargement.
AB  - We present a case of a thirty years old man who had suprapubic prostatectomy in
      our department. Patient's history started from the age of 25, when he experienced
      multiple urinary retention attacks. Imaging revealed an enormous prostatic mass.
      Combining this finding with elevated PSA values, lead us to prostatic biopsies
      which proved to be benign. Following our advice, the patient had children and
      afterwards he had his prostate removed. The suprapubic prostatectomy was
      extremely challenging with a lot of technical difficulties, considering that the
      net weight of the removed adenoma was 250gr. Pathological examination of the
      tissue proved that it was benign prostatic hyperplasia. Our case is particularly
      interesting for two reasons: On one hand because of the unusual size of the
      prostate and on the other hand because of the young age of the patient.
      Epidemiological studies showed that prostatic hyperplasia has been pathologically
      proved only after the age of 40, while pathological signs of the disease could be
      found after the age of 30. Concerning the size of the adenoma, a search in the
      literature showed that only 4% of the removed glands weight more than 100 gr, and
      that has to do with men over 70 years of age. Concluding, our case seems to be
      extremely rare. Furthermore, our search through the literature could not reveal
      any similar case report.

PMID- 20812538
TI  - Metastasis to the renal hilum from malignant melanoma of the anterior trunk: an
      unusual finding.
AB  - A retroperitoneal metastasis from malignant melanoma is an uncommon event and
      mostly secondary to a primary lesion of the posterior trunk. We report on a 38
      year-old patient with malignant melanoma of the anterior trunk who presented a
      symptomatic metastatic mass of the left renal hilum not originating from the
      retroperitoneal lymph nodes of the renal hilum, surrounding and infiltrating the
      renal pelvis, treated with left nephrectomy, complete mass excision and regional
      lymph node dissection. The patient later developed also brain metastases and is
      now undergoing immunotherapy.

PMID- 20812539
TI  - Interstitial cystitis with plasma cell bladder infiltration: case report and
      literature review.
AB  - We report the case of a 76 ys-old woman with overactive bladder syndrome,
      determined by an histological exam of interstitial cystitis with plasma cell
      infiltration. To the best of our knowledge, in literature only a similar case has
      been described. The patient has been treated with corticosteroid therapy allowing
      a transitory benefit; despite this fact, after side effects have been shown, this
      therapy has been interrupted leading to the worsening of the previous
      sintomatology. Therefore the patient has undergone to radical cystectomy with
      orthotopic ileal neobladder. The phlogistic infiltration of the bladder wall is
      represented by the plasma cells for over 90% of the whole population. In
      addition, blood specimen was positive for perinuclear antineutrophil cytoplasmic
      antibodies (p-ANCA). All these elements could hint at a chronic cystitis due to
      autoimmune aetiology.

PMID- 20812540
TI  - Lidocaine spray administration during transrectal ultrasound guided prostate
      biopsy modified the discomfort and pain of the procedure: results of a randomized
      clinical trial.
AB  - OBJECTIVES: We report the results of a study about the possible benefit of
      lidocaine spray perineal administration before transrectal ultrasound guided
      biopsy of the prostate. Many patients frequently report some kind of discomfort
      and (or) pain during this procedure, that when pain is severe, may be necessary
      to interrupt. MATERIALS AND METHODS: Between September 2007 and October 2009 372
      consecutive male patients with elevate PSA and (or) abnormal digital rectal and
      (or) suspect TRUS were scheduled for prostate biopsy and divided in 3 groups.
      Group 1 (n = 98) underwent intrarectal instillation of a lidocaine/prilocaine
      cream (EMLA R), Group 2 (n = 126) of a 2.5% lidocaine gel, and Group 3 (n = 148)
      administration of a lidocaine spray (10 gr/100 ml) before the procedure. A verbal
      numerical pain score (VNS) from = 0 no discomfort to 10 = severe pain was
      admnistrated to the biopsied patients who were asked to evaluate separately the
      degree of pain associated with the insertion of the probe and the manoeuvres
      associated with it and the degree of pain associated with the biopsy. RESULTS:
      The mean value of pain VNS in patients of the first group was respectively 5.3 (2
      8) for the insertion of the probe (first question) and 3.2 (2-7) for the biopsy
      by itself (second question), whereas in the second group it was 6.2 (4-9) and 3.8
      (3-8), and in the third group 3.1 (1-6) and 2.8 (0-6). CONCLUSIONS: Pain score
      results showed that the use of intrarectal lidocaine spray provided significantly
      better pain control than cream and anaesthetic gel. Our pain score data suggests
      that lidocaine spray provides efficient patient comfort during prostate biopsy by
      reducing pain both during probe insertion and insertion of the needle through the
      prostate gland. The use of lidocaine spray makes an excellent alternative,
      causing a reduction of anal sphincter tone with better patient compliance and
      tolerability to the ultrasound probe during biopsies with an optimization in
      terms of cost-effectiveness of the procedure.

PMID- 20812541
TI  - Extracorporeal shock wave therapy in the treatment of Peyronie's disease: long
      term results.
AB  - PURPOSE: Controversial data on ESWT (Extracorporeal Shock Wave Therapy) for the
      treatment of Peyronie's disease are controversial. This study was performed to
      access the efficacy, reliability and the side-effects of the ESWT. MATERIALS AND
      METHODS: From 2000 to 2004, 157 patients with an average age of 58 years and with
      Peyronie's disease were enrolled for a conservative treatment. All 150 eligible
      patients were treated with ESWT, using Dornier Compact Delta II UIMS
      lithotripter. The median number of treatments per patient was 3.5 with the
      delivery of 2000 shock waves (SW) for each treatment. There was no use of
      anaesthesia and analgesy. An ultrasound study was made for each patient before
      treatment. We considered: plaque size, penis curvature, pain, penis rigidity and
      tumescence, sexual intercourse ability and side-effects. Median follow-up of the
      study was 36.9 months. RESULTS: Average duration of the treatment was 20 minutes
      without relevant side-effects. With reference to the curvature, we obtained a
      significative reduction in 33.3% of the patients, whereas the plaque size was not
      statistically reduced. Regarding the pain issue we achieved good results with a
      reduction in more than 90% of the patients and a complete relief in 6%. The
      quality of the intercourse was reported slightly enhanced. No significant
      difference was observed in penis tumescence and rigidity. CONCLUSIONS: ESWT is a
      non-invasive treatment for the Peyronie's disease. Our study confirms that the
      best results are obtained regarding pain and less with the curvature. For the
      plaque size and quality of sexual intercourse the results are not satisfactory.

PMID- 20812542
TI  - [Quality assurance in nursing--too much of a good thing!].

PMID- 20812543
TI  - [Joint interim report of basic nursing support points : of successes, hopes and
      national insurance as cooperating partners].

PMID- 20812544
TI  - [Study of nursing science in Italy: more than pasta and Berlusconi].

PMID- 20812545
TI  - [15 years nursing insurance--amended in 2008: "all are challenged" (interview by
      Ivonne Rammoser)].

PMID- 20812546
TI  - [Nursing risk management in nursing facilities: recognizing hazards--minimizing
      risks].

PMID- 20812547
TI  - [An orientation for nurses and nursing care recipients: guiding principles-
      stepchildren of the nursing industry?].

PMID- 20812548
TI  - [Shortcomings and possible improvements in nursing care: postoperative pain
      therapy begins preoperatively].

PMID- 20812549
TI  - [Reflections on language in nursing care--2: A contribution to
      professionalization].

PMID- 20812550
TI  - [About iron in spinach, vitamins, fats, water and sunlight: nutrition myths and
      facts].

PMID- 20812551
TI  - [Video game consoles introduced in geriatric nursing homes. Competitive bowling
      with Wii].

PMID- 20812552
TI  - [Temporary employment--better known as personnel leasing: also viewed as an
      opportunity].

PMID- 20812553
TI  - [Standardization of ethics committees in health care and nursing facilities:
      future perspectives for sustainable and effective counseling].

PMID- 20812554
TI  - [Masculinity and femininity in self-perceptions and ideals of registered nurses].
AB  - Despite of intensive professionalisation efforts and changed legal frameworks the
      public image of nursing is still full of gender-stereotypes. This study
      investigates to what extend public stereotypes of "typically female" and
      "typically male" are reflected in the self-concept and ideals of nurses. Using a
      cross-sectional research design 174 female nurses were surveyed regarding their
      sex-role orientation and ideals (femininity and masculinity) using a standardized
      questionnaire (BSRI). Contrary to stereotypes the respondents indentified more
      with masculine traits. Masculine attributes predominated especially in ideas
      about the ideal nurse. No differences between nurses who work in different areas
      could be revealed. In all endeavors regarding autonomy and masculinity the
      significance of the feminine function of "caring" must not be forgotten. Teachers
      in healthcare and nursing play a central role in sensibilising students for
      gender issues.

PMID- 20812555
TI  - [Quality control and quality assurance in nursing facilities: the auditor
      received as a guest].

PMID- 20812556
TI  - [From complaints to consumer satisfaction: every complaint is an opportunity].

PMID- 20812557
TI  - [From case to case: reducing safety risks in managing medications].

PMID- 20812558
TI  - [Wrong to routinely deny smokers care].

PMID- 20812559
TI  - [Transplantations and concept confusion. Living donor, dead donor].

PMID- 20812560
TI  - [Breakthrough for transcatheter aortic valve implantation. But "evidence-based
      experience" has not kept up].

PMID- 20812561
TI  - [Nephropathia epidemica: Data on voles indicate new, extensive outbreak].

PMID- 20812562
TI  - [Permanent hearing loss following dog bite. Capnocytophaga canimorsus caused
      severe infection with sepsis].

PMID- 20812563
TI  - [Intermittent claudication].

PMID- 20812564
TI  - [Regional HTA work can have a good impact on health care. Good examples form
      Vastra Gotaland].

PMID- 20812565
TI  - [Internship supervisor--an impossible mission?].

PMID- 20812566
TI  - [Research is the future of psychiatry!].

PMID- 20812567
TI  - [When the patient can't consent to participation in a trial: the Ethics Review
      Board should take over the decision responsibility from the relatives].

PMID- 20812568
TI  - [Lean--without support, no success].

PMID- 20812569
TI  - [New health insurance rules no obstacles for good prognosis in fatigue syndrome].

PMID- 20812570
TI  - [What do the Swedish Drug and Therapeutics Committees think about cost savings?].

PMID- 20812572
TI  - [Panorama of golf injuries].

PMID- 20812571
TI  - ["Ceratophyllus" might have been bird mites].

PMID- 20812573
TI  - [Important discoveries by the universal genius passed unnoticed].

PMID- 20812574
TI  - Compartment syndrome surgical management techniques associated with tibial
      plateau fractures.
AB  - Compartment syndrome is an orthopaedic emergency that can be challenging to
      diagnose and manage when associated with a tibial plateau fracture. This
      technique article discusses one- and two-incision fasciotomy surgical techniques,
      and the surgical decision making and technique modifications when there is an
      associated tibial plateau fracture.

PMID- 20812575
TI  - Acute compartment syndrome in tibial plateau fractures--beware!
AB  - Acute compartment syndrome can complicate fractures of the tibial plateau and
      must be recognized early so that timely fasciotomy can be performed. The presence
      of the open fasciotomy wound complicates management of the underlying proximal
      tibial fracture, which ideally needs early anatomic reconstruction of the
      articular surface and stable metaphyseal fixation. The purpose of this review is
      to highlight the importance of this problem, understand treatment strategies, and
      review outcomes.

PMID- 20812576
TI  - Acute crystal-induced arthritis following arthroplasty.
AB  - Septic arthritis at the site of previous arthroplasty is a serious medical
      problem with high morbidity and mortality. Even with careful physical examination
      and laboratory evaluation, the diagnosis of septic arthritis may be difficult to
      confirm and many patients undergo operative procedures for presumed infection. In
      patients with previous arthroplasty, a synovial fluid white blood cell count of >
      2500-3000/mm3 in the presence of an elevated erythrocyte sedimentation rate and C
      reactive protein has been reported to indicate infection with a high degree of
      sensitivity and specificity. However, crystal-induced disease (gout, pseudogout)
      may present with the extact same clinical manifestations, physical examination,
      and laboratory results as infection. Yet crystal-induced disease is only rarely
      recognized in patients with previous arthroplasty. We report two cases of acute
      crystal disease in patients with previous arthroplasty that mimicked infection.
      Review of the few additional case reports extent suggests that crystal-induced
      disease may occur more frequently than heretofore recognized. We therefore
      propose that the evaluation of acute arthritis in a patient with previous
      arthroplasty include systematic evaluation for crystal disease, as patients may
      present with septic arthritis, crystal disease, or both.

PMID- 20812577
TI  - Bicondylar Hoffa fracture: open reduction internal fixation using the
      swashbuckler approach.
AB  - Coronal plane fractures of the femoral condyle are infrequent injuries and are
      often missed. Unilateral bicondylar coronal plane fractures are even rarer, with
      only eight reported cases in scientific literature, and are often associated with
      other injuries. We present here a case of unilateral bicondylar Hoffa fracture
      that presented in our emergency department and was managed with open reduction
      and internal fixation by lateral parapatellar arthrotomy using the swashbuckler
      approach with satisfactory results.

PMID- 20812578
TI  - Synovial hypertrophy causing recurrent hemarthrosis after total knee replacement.
AB  - Recurrent hemarthrosis following total knee replacement is relatively uncommon
      and can result from causes that may not always be easy to diagnose. We report
      three patients with late-onset recurrent hemarthrosis following total knee
      replacement due to synovial hypertrophy and impingement, which were successfully
      treated by embolization.

PMID- 20812579
TI  - AperFix versus transfix in reconstruction of anterior cruciate ligament.
AB  - The aim of this retrospective study was to compare clinical outcomes of the
      TransFix (Arthrex Inc., Naples, FL) fixation method and the brand-new AperFix
      (Cayenne Medical, Scottsdale, AZ) device in arthroscopic reconstruction of
      anterior cruciate ligament. A total of 38 patients with isolated complete
      anterior cruciate ligament rupture underwent arthroscopic reconstruction via two
      different fixation methods using hamstring autografts. Patients were evaluated in
      terms of range of motion values, Lysholm scores, laxity testing, and
      complications. Average flexion was 136.53 +/- 6.9 degrees in the TransFix group
      and 126.32 +/- 4.9 degrees in the AperFix group (p < 0.001). Mean Lysholm score
      was 82.42 +/- 8.5 in the TransFix group and 88.68 +/- 9.4 in the AperFix group (p
      < 0.022). There was no significance between the two groups in terms of laxity
      testing and complication rates. In the early postoperative period, satisfactory
      and comparable clinical results were achieved with the AperFix system when
      compared with cross-pin fixation in arthroscopic anterior cruciate ligament
      reconstruction.

PMID- 20812580
TI  - Evaluation of a Schanz pin technique for posterior cruciate ligament tensioning
      during reconstruction.
AB  - Maximum anterior positioning of the tibia relative to the femur during posterior
      cruciate ligament (PCL) reconstruction is essential for achieving a tight graft
      and stable joint. A Schanz pin inserted in the proximal tibia is sometimes used
      to pull the proximal tibia forward during tensioning of the graft in PCL
      reconstruction. This study was designed to evaluate whether this technique
      provides more anterior translation than the traditional anterior drawer
      technique. Eight fresh-frozen cadaveric knees were tested using both methods in
      randomized order: pulling anteriorly on a 5-mm Schanz pin in the proximal tibia
      or a leather strap behind the calf designed to simulate a surgeon's hand
      performing an anterior drawer maneuver. An anteriorly directed force was applied
      from 0 to 60 N, and the sagittal position of the tibia in relation to the femur
      was recorded using a mini C-arm. Tests were performed first on the intact knees,
      again after the PCL had been cut, and again following transection of the
      popliteal-fibular ligament. We found a statistically significant (p < 0.05)
      increase in tibial translation, ranging between 1 and 2 mm, when the tibia was
      pulled by the Schanz pin compared with the strap under every set of conditions.
      This greater anterior translation could improve the stability of the
      postreconstructed knee.

PMID- 20812581
TI  - Magnetic resonance imaging osteonecrosis pattern within an osteochondral dowel
      allograft.
AB  - A 22-year-old male with a history of a previously debrided large posttraumatic
      osteochondral lesion of the lateral femoral condyle presented to our institution
      for further treatment due to persistent pain and instability. He was treated with
      a large cryopreserved osteochondral dowel allograft and remained clinically
      asymptomatic with no pain, locking, or instability at his 12-month, 18-month, and
      42-month follow-up appointments. However, his 12-month magnetic resonance imaging
      (MRI) examination demonstrated an osteonecrosis pattern within the osseous
      component of the allograft. Six months later, the osteonecrosis pattern decreased
      in size, and 30 months later had completely resolved. The allograft was otherwise
      stable in appearance. The MRI appearance was most likely due to a normal
      maturation process of bone healing within osteochondral allograft dowel, referred
      to as "creeping substitution".

PMID- 20812582
TI  - Predictors of bone loss in revision total knee arthroplasty.
AB  - Revision total knee arthroplasty (RTKA) requires preoperative planning to enable
      the reconstruction of bony deficiencies. The objective of this project was to
      identify predictors of bone loss management at RTKA based on the preoperative
      failure mode and patient demographics known preoperatively. We retrospectively
      reviewed 245 consecutive RTKA procedures in which the same revision knee system
      was utilized. Patient demographic and treatment data were recorded, and locations
      of bone loss were identified based on the reconstructive management. We
      identified significant predictors for use of femoral augments at all four
      positions. Several predictors significantly predisposed to use of a thick (>19
      mm) polyethylene; however, no predictors of tibial augments were significant.
      Although the reconstruction of bone loss is primarily based on the intraoperative
      assessment, these findings may provide additional information to help the surgeon
      prepare for difficult revision procedures.

PMID- 20812583
TI  - [Forgotten children--the status of children of mentally ill parents].

PMID- 20812584
TI  - [What is good pediatric hospice work?].

PMID- 20812585
TI  - [Promoting confidence in therapeutic interventions--information between truth and
      truthfulness].

PMID- 20812586
TI  - [Bauchgefuhl--preventative approach to eating disorders in adolescents].

PMID- 20812587
TI  - [Healthy students].

PMID- 20812588
TI  - [Children as family of parents with mental illnesses].

PMID- 20812589
TI  - [Etiology and prevention of hospital acquired infections exemplified by venous
      catheter associated infection].

PMID- 20812590
TI  - [Comment on the article "Boys are the stupid ones"].

PMID- 20812591
TI  - [One year of Balthasar pediatric hospice nursing].

PMID- 20812592
TI  - Healthcare IT support: recommendations for a critical need.

PMID- 20812593
TI  - Roam if you want to. Offering everything from videoconferencing to security
      enabled medication management, these aren't your grandfather's carts.

PMID- 20812594
TI  - Is an EHR regional extension center right for you? To assist eligible providers,
      regional extension centers were funded to move practices from paper-based to EHR
      based documentation, but there are other ways to accomplish the same result.

PMID- 20812595
TI  - Automated referrals close the communications loop. Boston Medical Center
      streamlines work flow and interoperability--and sees a huge return on investment-
      using Carefx eReferral portal.

PMID- 20812596
TI  - Transcription makeover. Virginia's Rockingham Memorial Hospital improves its
      clinical documentation process by implementing advanced speech-recognition
      technologies.

PMID- 20812597
TI  - Evaluating EHR systems. What practice owners should consider when looking at
      electronic health records systems.

PMID- 20812599
TI  - Voice recognition: the key to hospital dominance. Although still three to five
      years away, digitized voice recognition and input may hold the key to a
      comprehensive electronic patient clinical record.

PMID- 20812598
TI  - Critical considerations mobile device deployments. The right device is dependent
      upon the user, where it will be used and the tasks being performed.

PMID- 20812600
TI  - Walking in the patients' shoes. PacMed adopts a real-time locating system to
      improve processes, safety and the bottom line.

PMID- 20812601
TI  - The meaningful use party finally begins.

PMID- 20812602
TI  - Risk assessment for hereditary breast cancer: BRCA1 and BRCA2.
AB  - The recent explosion of hereditary breast cancer genetic research has
      strengthened our understanding of genetic influences on health and disease. These
      scientific advances have significant implications for clinical oncology nurses
      and advanced practice nurses. In this paper, the Human Response to Illness Model
      (Mitchell, Gallucci, & Fought, 1991) is utilized to gain a comprehensive
      understanding of breast cancer related to the human response of genetic
      mutations. Accordingly, the research literature related to the physiological,
      pathophysiological, behavioural, and experiential perspectives of BRCA-related
      breast cancer will be highlighted. This research-based evidence will provide
      oncology nurses with the skills to establish a holistic plan of care for women
      with an actual or potential genetic risk for breast cancer.

PMID- 20812603
TI  - Will designated patient navigators fix the problem? Oncology nursing in
      transition.
AB  - With increasing concern for equity and access across the cancer care system, we
      have seen expanding enthusiasm for various forms of designated patient
      "navigators" to facilitate coordination. While the intention is laudable, many of
      the popular implementation strategies risk accentuating strain upon the system
      and further complicating the coordination problem. These authors claim the
      motivation underlying the navigator movement can be reframed as an emerging
      recognition of the value of nursing work when it is optimally positioned to
      support patients, as they experience the cancer care system. This paper calls on
      Canadian oncology nurses to critically challenge navigation strategies, and adopt
      only those consistent with the significant reforms required to ensure a cancer
      care system so effective that external navigators are no longer necessary.

PMID- 20812604
TI  - Schering Plough Lecture 2009. The twinning experience: meaning of an educational
      program for nurses in Kenya.

PMID- 20812605
TI  - Adult survivorship--a self-learning module for nurses developed by CANO/ACIO
      nurses.

PMID- 20812606
TI  - Oncology nursing: a calling, a career or both?

PMID- 20812607
TI  - Clinical tip--the use of interpreters in clinical settings.

PMID- 20812609
TI  - GPs should evaluate all children following UTI.
AB  - Ten per cent of girls and 3% of boys will have had a UTI by 16 years of age. The
      majority are acute, isolated illnesses that resolve quickly, with no long-term
      implications for the patient. However, UTIs may be associated with underlying
      congenital abnormalities, and recurrent infections can lead to renal scarring.
      UTI is defined as bacteriuria in the presence of symptoms. Asymptomatic
      bacteriuria does not require treatment or investigation. The presentation of UTI
      is extremely variable. The only way to differentiate a UTI from a viral infection
      is by testing the urine and this should be carried out within 24 hours in
      children with non-specific fever. UTIs can also present with vomiting, failure to
      thrive or persistent irritability. A urine infection in the presence of any of
      the above symptoms is a pyelonephritis (upper UTI). Children may also present
      with classical symptoms of cystitis (lower UTI) such as urinary frequency,
      dysuria and abdominal pain. Most children with UTI, even if febrile, can be
      managed in the community. If the initial assessment shows a high risk of serious
      illness, there should be an urgent referral to a paediatrician. The same applies
      to infants under three months with suspected UTI. It is better to obtain a urine
      sample by the clean catch method, rather than using urine pads or bags. Leucocyte
      esterase and nitrite dipsticks are not reliable in children under three, so a
      negative dipstick does not rule out UTI. Not every child needs to be referred
      after a first UTI. However, they should all be evaluated to help determine which
      require renal imaging as well as identifying triggers for recurrence. GPs are
      central to the identification of children at risk of renal pathology. All
      children who are diagnosed and treated for a UTI must be assessed for risk of
      renal abnormalities and/or recurrence.

PMID- 20812610
TI  - Education key in tackling childhood constipation.
AB  - Constipation is the most common childhood gastroenterological problem, affecting
      5-30% of children. Up to a third of these children will develop chronic
      constipation. The signs and symptoms of constipation in children are seldom clear
      and there is often a delay in seeking help in either a primary or secondary care
      setting. The underlying cause of childhood constipation is unclear. The initial
      problem may be an acute episode of constipation that results in painful
      defecation. This may lead to the development of an anal fissure and the child may
      become scared of the process of defecation. Often they will hold on to the faeces
      which become harder and when they are passed cause pain and so the vicious cycle
      is repeated. The key to the effective management of childhood constipation is
      establishing the diagnosis of idiopathic constipation by taking a thorough
      history. Up to 29% of children with daytime urinary incontinence may have chronic
      constipation and 34% of children with chronic constipation older than five years
      may have problems with bedwetting. Chronic constipation is often a risk factor
      for recurrent UTIs in children. Urinary retention and vulvovaginitis have also
      been described in children with chronic constipation. It is important to explain
      to the patient and parents that the symptoms have a medical explanation and that
      the child has not been soiling because of bad behaviour. Once the child has been
      diagnosed with idiopathic constipation, it is important to assess him or her for
      faecal impaction as this will determine the next therapeutic step. Faecal
      impaction can be diagnosed by history taking and examination.

PMID- 20812608
TI  - MI admissions fall following smoking ban in England.

PMID- 20812611
TI  - Improving the management of neuropathic pain.
AB  - Neuropathic pain is defined as 'pain arising as a direct consequence of a lesion
      or disease of the somatosensory system'. It may reflect a widespread neuropathic
      process (e.g. diabetic neuropathy) or a more focal disorder (e.g. post-herpetic
      neuralgia). The practical importance of recognising neuropathic pain (as distinct
      from nociceptive pain) lies in the difference in effective treatments. The
      patient may be experiencing more than one type of pain. Many long-term disabling
      neurological disorders, such as multiple sclerosis, as well as causing
      neuropathic pain, may also give rise to musculoskeletal pains which may be more
      readily amenable to treatment. Most treatment for long-term pain, including
      neuropathic pain, should be provided in primary care, with specialist support.
      When taking the history it is important to elicit information about the site,
      duration, intensity and character of the pain, or pains, and what precipitates
      and relieves it. Accompanying somatosensory disturbance in the painful territory
      (numbness; allodynia; hyperalgesia; paraesthesia and dysaesthesia) is strongly
      suggestive of neuropathic pain. A specialist opinion should be sought where the
      diagnosis is uncertain, or the patient's condition is rapidly deteriorating or
      uncontrolled. This may be a specialist in a particular condition, to address
      issues of primary diagnosis, or a specialist in pain medicine to advise on, or
      provide, further treatment. Patients who are struggling with their pain are best
      served by specialist centres that can endeavour to explain the condition and
      encourage self-management.

PMID- 20812612
TI  - Unusual conditions.

PMID- 20812613
TI  - The teaching of insanity to the medical practitioner. 1910.

PMID- 20812615
TI  - [Recent advances in chromatography].

PMID- 20812616
TI  - [Application of chromatography in environmental monitoring. Foreword].

PMID- 20812618
TI  - [Applications of large-volume injection for environmental analysis].
AB  - Large-volume injection (LVI) in capillary gas chromatography (CGC) was developed
      for determining the trace components in environmental samples and for reducing
      (or even eliminating) the need for cleanup step, also for on-line connection of
      liquid chromatography (LC) with CGC. The key features of the LVI include sample
      retained by a large capacity volume liner or a retention gap, and solvent vapor
      eliminated by solvent vapor exit. There are many kinds of LVI techniques for
      different analyses, capillary columns and purposes. This review summarizes the
      recent developments of LVI for environmental analysis, include on column
      injection (OCI), programmed temperature vaporizer (PTV), AT-column, direct sample
      introduction/difficult matrix injection, concurrent solvent recondensation large
      volume splitless injection, and also through oven transfer adsorption desorption
      interface for on-line connection of LC with CGC.

PMID- 20812617
TI  - [Applications of chromatography-mass spectrometry for the analysis of emerging
      organic pollutants].
AB  - Emerging organic pollutants are becoming the focus of current research on
      environmental issues. Chromatography coupled to mass spectrometry (MS) has played
      key roles in the discovery and analysis of emerging organic pollutants. This
      review summarizes the developments in chromatography-MS techniques for five
      important emerging organic pollutants, including
      perfluorooctanoate/perfluorooctanesulfonate (PFOA/PFOS) and other perfluorinated
      compounds, pharmaceuticals, drinking water disinfection byproducts, pesticide
      degradation products and new pesticides, and brominated flame retardants. The
      future trends of chromatography-MS in this field are also discussed.

PMID- 20812619
TI  - [Determination of polychlorinated biphenyls and polybrominated diphenyl ethers in
      ambient air using high volume sampling and high resolution gas
      chromatography/high resolution mass spectrometry].
AB  - A method for the determination of polychlorinated biphenyls (PCBs) and
      polybrominated diphenyl ethers (PBDEs) in ambient air using high volume sampling
      and high resolution gas chromatography coupled with high resolution mass
      spectrometry (HRGC/HRMS) was developed. The results indicated that no
      breakthrough happened during the sampling procedure. The recoveries of 13C
      labelled compound standards of PCBs and PBDEs were in the ranges of 60.7%-121.4%
      and 69.9%-140.4%, respectively, which were qualified by the corresponding EPA
      methods. The limits of detection (LODs) of PCBs and PBDEs in real samples were
      lower than 0.019 pg/m3 and 0.189 pg/m3, respectively. The chromatograms of PCBs
      and PBDEs show good performance in the separation. It is demonstrated that the
      method is suitable for the determination of PCBs and PBDEs in ambient air.

PMID- 20812620
TI  - [Determination of indicator toxaphene in soil by isotope dilution-gas
      chromatography-tandem mass spectrometry].
AB  - Although toxaphene is now banned in use, the analysis of toxaphene has attracted
      increasing interest due to its persistence and widespread atmospheric transport
      in the environment. A new method based on isotope dilution-gas chromatography
      tandem mass spectrometry (ID-GC-MS/MS) has been developed for the determination
      of three toxaphene specific congeners comprised of Parlar No. 26 (P26), Parlar
      No. 50 (P50) and Parlar No. 62 (P62) in soil. (13)C10-labeled indicator toxaphene
      solution was added to the sample prior to pretreatment. Then the sample was
      extracted using pressurized liquid extraction (PLE) followed by purification on
      multilayer acidic silica column and neutral silica column. The eluent was
      concentrated under gentle nitrogen gas flow and spiked with the injection of
      internal standard of (13)C10-chlordane. Identification and quantification of the
      analytes were carried out in the multiple reaction monitoring (MRM) mode after
      the GC separation. The linear range was 20-800 microg/L for three congeners,
      limits of detection (LOD) ranged from 3.0 to 6.0 pg. The five point calibration
      curves showed a good linearity for all the congeners (R2 > 0.99). The relative
      standard deviations (RSDs) were below 11% for and the spiked recoveries were in
      the range of 55%-110%. The developed analytical method is suitable for the
      determination of toxaphene specific congeners in soil.

PMID- 20812621
TI  - [Determination of trace organochlorine pesticides in soil using isotope dilution
      high resolution gas chromatography].
AB  - A method for the determination of trace organochlorine pesticides (OCPs) in soil
      using isotope dilution and high resolution gas chromatography-high resolution
      mass spectrometry (ID-HRGC-HRMS) was developed. The sample was extracted by
      accelerated solvent extractor (ASE) and cleaned-up by a Florisil solid phase
      extraction (SPE) cartridge. The analytes were separated by HRGC on a DB-5MS
      column (30 mx 0.25 mm x 0.25 microm) and determined by HRMS. The identifications
      of OCPs were based on the retention time of 13C-labelled standard and the
      abundance ratio of the two exact mass-to-charge ratios. The quantitative analysis
      was performed using the ratios of the integrated areas of the 13C-labelled
      standards. This method has the recoveries ranging from 77.3% to 114.5% and the
      relative standard deviations (RSD) less than 10.81% (n=5). The limits of
      detection (LODs) of this method for all OCPs were lower than 0.04 pg/g. The
      results indicated that the method is rapid, selective and sensitive for precise
      determination requirements of organochlorine pesticides at trace level in soil.

PMID- 20812622
TI  - [Quality assurance/quality control for the determination of polycyclic aromatic
      hydrocarbons and phthalate esters in soils using gas chromatography-mass
      spectrometry].
AB  - A method for the determination of polycyclic aromatic hydrocarbons (PAHs) and
      phthalate esters (PAEs) in soil samples by gas chromatography-mass spectrometry
      (GC-MS) was developed. After extracted by accelerated solvent extraction or
      ultrasonic extraction by dichloromethane-hexane (1:1, v/v) and dichloromethane
      acetone (1:1, v/v), respectively, the extracts were cleaned up by solid phase
      extraction and/or gel permeation chromatography. Quality control and quality
      assurance procedures were carried out with the methods of whole procedure blank,
      blank spike recovery, clean soil matrix spike recovery, and the comparison with
      reference materials. The method detection limits were 0.13-2.2 microg/kg and 0.19
      0.52 microg/kg and the average recoveries were 41.5%-116.9% 90.7%-107.1% for the
      PAHs and the PAEs, respectively. The results showed that the method can meet the
      technical requirements on the soil sample test and analysis in the national
      survey of soil pollution.

PMID- 20812623
TI  - [Veracity on determination of organic compounds in the air by portable gas
      chromatography-mass spectrometry].
AB  - Portable gas chromatography-mass spectrometry (GC-MS) can simultaneously carry
      out qualitative and quantitative analysis of multi-component complex organic
      compounds. Because of its characteristics, portable GC-MS plays an increasingly
      important role in environmental monitoring, especially in the spot emergent
      monitoring. In this study, performance of portable GC-MS on determination of low
      concentration of volatile organic compounds (VOCs) in ambient air was compared
      with EPA TO-14A method, and the accuracy of high concentrations of VOCs
      determined by loop ring model was examined. Results indicated that detection
      limits of VOCs in air HAPSITE portable GC-MS was equivalent to that of EPA TO-14A
      method, while accuracy and precision is slightly lower, but all accord with the
      requirements of environmental monitoring and analysis. The loop ring can be used
      in the emergent pollution accidents for it can accurately analyze samples in high
      concentration of VOCs in the grade of 10(-6).

PMID- 20812624
TI  - [Determination of organochlorine pesticide residues in soil/sediment using
      isotope dilution gas chromatography-mass spectrometry].
AB  - A method was developed for the determination of organochlorine pesticide (OCP)
      residues in soil/sediment using high resolution gas chromatography coupled with
      low resolution mass spectrometry. The analytical procedures consisted of Soxhlet
      extraction, sulfur removal with copper powder, clean-up with gel permeation
      chromatography (GPC) and a florisil column of solid phase extraction (SPE). The
      analytes were separated on an HP-5MS capillary column, detected in selected ion
      monitoring ( SIM) mode and quantified using internal standard calibration curves
      of isotope dilution technique. The linear correlations of calibration standard
      solutions were good for all the OCPs. The recoveries and relative standard
      deviations of labeled compound solutions ranged from 60% to 110% and from 1.5% to
      18%, respectively. The limits of detection ranged from 0.20 to 10.3 microg/kg
      were established for the 23 OCPs. The method showed satisfactory clean-up effect
      and precision quantification. It is suitable for the determination and
      confirmation of pesticides in complex matrices such as soil, sediment.

PMID- 20812626
TI  - [Determination of phthalate esters in sediment by accelerated solvent extraction
      and gas chromatography-triple quadrupole mass spectrometry].
AB  - A method for the determination of seventeen phthalate esters in sediment by
      accelerated solvent extraction (ASE), gel-permeation chromatography (GPC) and gas
      chromatography-triple quadrupole mass spectrometry (GC-MS/MS) has been developed.
      The target compounds were extracted at 100 degrees C and 103.4 MPa (1500 psi) by
      ASE using the mixtures of dichloromethane and acetone (1:1, v/v) as solvent. In
      order to eliminate the interferences from larger molecular sizes, the extract was
      purified at a flow rate of 5.0 mL/min by GPC. Following that, the extract was
      concentrated to a final volume of 1 mL exactly. The GC-MS/MS was applied to
      quantitative and qualitative analysis. Internal standard calibration approach was
      adopted, and the detection limits of seventeen phthalate esters ranging from 0.05
      to 0.40 microg/kg were obtained. The correlation coefficients were beyond 0.996,
      the recoveries were from 50.5% to 107.9%, and the relative standard deviations
      were from 3.5% to 13.9%. Besides, the surrogate compounds spiked were used to
      monitor the performance of the method, and the recoveries were from 65.3% to
      95.8% for the three surrogate compounds. The method is fast, sensitive and exact
      for analyzing seventeen phthalate esters simultaneously.

PMID- 20812625
TI  - [Preparation of soil candidate reference materials for the analysis of
      organochlorine pesticides in soils].
AB  - The preparation method of new soil candidate certified reference materials (CRM)
      for the analysis of organochlorine pesticides in soils has been developed. The
      soil sample was dried, ground, homogenized and packed. After Soxhlet extraction
      and Florisil purification, the organochlorine pesticides in soil candidate were
      further determined using gas chromatography-mass spectrometry. The results showed
      that the soil collected from Shenyang was an ideal soil candidate material for
      organochlorine pesticide analysis. This method established a foundation for the
      development of soil reference materials for the analysis of organochlorine
      pesticides.

PMID- 20812627
TI  - [Determination of 22 antibiotics in environmental water samples using high
      performance liquid chromatography-electrospray ionization tandem mass
      spectrometry].
AB  - A method for the determination of 22 antibiotics in environmental water samples
      was developed by using high performance liquid chromatography-electrospray
      ionization tandem mass spectrometry (HPLC-ESI MS/MS). The target antibiotics in
      water samples were enriched and cleaned-up by HLB solid-phase extraction (SPE)
      cartridges, and then eluted with 6 mL ammonium hydroxide-methanol (5:95, v/v).
      The eluate was collected and concentrated to 1 mL under a gentle stream of
      nitrogen gas, and then analyzed by HPLC-ESI MS/MS in positive electrospray
      ionization and multiple reaction monitoring (MRM) mode. The separation was
      carried out on an XTerra MS C18 column with mobile phases of A, methanol
      acetonitrile (1:1, v/v), and B, 0.3% formic acid/water (containing 0.1% ammonium
      formate, v/v, pH 2.9). The results showed that the average recoveries of
      antibiotics in tap water and wastewater were 54.9%-130% and 57.4%-138%,
      respectively, and the corresponding relative standard deviations (RSD, n=3) were
      2.85%-28.6% and 2.02%-23.2%, respectively. The method detection limits were 0.05
      0.5 ng/L. The developed method was applied to analyze the water samples of
      Gaobeidian Lake and Xiaoqinghe River in Beijing. The results showed that some
      antibiotics were detected both in the two samples.

PMID- 20812628
TI  - [Analysis of perfluorinated compounds in sludge by liquid extraction and high
      performance liquid chromatography-tandem mass spectrometry].
AB  - Perfluorinated compounds are emerging persistent organic pollutants. Wastewater
      treatment plants are reported to be one of their primary sources. However, a
      standard analytical method for sludge samples has not been set up. A novel and
      rapid analytical method based on the liquid extraction, followed by high
      performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was set
      up for 7 perfluorocarboxylic acids (PFCAs) and their precursors, 6:2 and 8:2
      unsaturated flourotelomer carboxylic acids (FTUCAs), and 2 perfluoroalkyl
      sulfonates (PFASs) and their precursors, 5 derivates of sulfonamide in sludge.
      The parameters of methanol extraction, including pH, sonication temperature and
      time, and eluent volume were optimized. The extraction method was optimized as
      neutral extraction under sonication at 40 degrees C for 10 min, and it was
      successfully used for the analysis of perfluorinated compounds in the sludge
      samples. The linear calibration curves were obtained in the ranges of 0.1-20
      microg/L for PFCAs and 6: 2/8: 2 FTUCA and 0.25-50 microg/L for PFASs and their
      precusors with linear correlation coefficients larger than 0.99. The recoveries
      of the target compounds ranged from 74% to 141% (except for FTUCAs) and the
      limits of quantification ranged from 0.6 to 30 microg/kg (dry weight). The use of
      internal standards can well correct the ion suppression (or enhancement) induced
      by co-eluting components present in the sample extracts, and improve the
      quantitative accuracy.

PMID- 20812629
TI  - [Determination of three perfluoro sulfonated chemicals in bivalve shells using
      high performance liquid chromatography-tandem mass spectrometry with the
      pretreatment of mixed inorganic acid digestion coupled with solid-phase
      extraction].
AB  - For the analysis of perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate
      (PFHxS) and perfluorooctane sulfonate (PFOS) in shells, an extraction method of
      mixed inorganic acid digestion coupled with solid phase extraction (SPE) was
      established. The target compounds were determined by high performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS/MS). The shell powder was at
      first digested with the mixture of nitric acid and hydrochloric acid, then the
      digestion solution was adjusted to pH 6 with sodium hydroxide, and cleaned up
      with Oasis WAX SPE cartridge. The perfluoro sulfonated chemicals were quantified
      with HPLC-MS/MS using electrospray ionization in negative ion mode with internal
      standard method. The limits of detection (LODs) were of 0.28 ng/g for PFBS, 0.42
      ng/g for PFHxS and 0.43 ng/g for PFOS, and matrix recoveries of the perfluoro
      sulfonated chemicals were 94.88%-96.24%. The analytical results for the shells of
      two bivalves from Bohai Bay showed this pretreatment method is suitable for the
      determination of perfluoro sulfonated acids (PFSAs) in shells. Concentrations of
      PFSAs in the shells ranged from < LOD-0.70 ng/g, which were an order of magnitude
      lower than those in the soft tissues of these bivalves.

PMID- 20812630
TI  - [Determination of bisphenol A in environmental water samples by stir bar sorptive
      extraction based on molecularly imprinted polymer].
AB  - A new stir bar sorptive extraction (SBSE) based on molecularly imprinted polymer
      (MIP) with bisphenol A as template was prepared. Based on it, a simple, selective
      and sensitive method for the determination of bisphenol A (BPA) was developed
      combined with high performance liquid chromatography (HPLC) with diode array
      detection. To achieve the optimum extraction performance, several main
      parameters, including extraction and desorption time, the nature of desorption
      solvent, pH value and contents of inorganic salt in the sample matrix, were
      investigated. The optimized parameters for the extraction of BPA from water
      matrix with the MIP-SBSE are as follows: extraction and desorption time were 120
      min and 10 min, respectively; the pH value of matrix was 10.0; using acetonitrile
      (including 1% acetic acid) as desorption solvent; no salt was added in the
      matrix. Under the optimized experimental conditions, the method showed good
      linearity between 1.0-200 microg/L. The detection limit (S/N = 3) and
      quantification limit (S/N = 10) of the proposed method for the BPA was 0.28
      microg/L and 0.94 microg/L, respectively. The proposed method was successfully
      applied to the determination of the target compound in water samples. The
      recoveries of spiked target compound in real samples ranged from 96.0%-108.7%.
      The results indicated that the developed method possessed the advantages such as
      high sensitivity, simplicity, low cost and environmental friendliness.

PMID- 20812631
TI  - [Determination of three polycyclic aromatic hydrocarbons in environmental water
      samples by disposable fibers of solid-phase microextraction coupled with high
      performance liquid chromatograph].
AB  - A method was developed for the determination of phenanthrene, fluoranthene and
      chrysene in environmental water samples using disposable fibers of solid-phase
      microextraction (SPME) coupled with high performance liquid chromatograph (HPLC).
      The disposable SPME fibers for the extraction were added into the sample (60 mL)
      spiked with 20 g/L NaCl. After extracted for 60 min at a stirring speed of 1200
      r/min, the fibers were collected and immersed in 120 microL methanol for 24 h to
      desorb the analytes for the HPLC analysis followed. Under the optimized
      conditions, the respective detection limits were 0. 17 microg/L for phenanthrene
      and fluoranthene, and 0.08 microg/L for chrysene, and the relative standard
      deviations (RSDs) were less than 8% (n=6). The method was successfully applied to
      analyze real environmental water samples with spiked recoveries in the range of
      80.0%-107%. This method is cost-effective, easy to operate, and overcomes the
      carry-over problem of the pollutants on the fibers.

PMID- 20812632
TI  - [Determination of phthalate esters in Baiyangdian Lake by solid phase
      microextraction and gas chromatography].
AB  - A simple method based on solid-phase microextraction (SPME) coupled with gas
      chromatography-flame ionization detection (GC-FID) was developed for the
      determination of trace amounts of phthalate esters (PAEs) in environment water
      samples. In this method, polydimethylsilane (PDMS) fiber was chosen to enrich the
      PAEs. The PAEs were extracted for 60 min using the PDMS fiber under stirring with
      a magnetic stir bar, after that the fiber was introduced into the GC injector
      port and the extract was desorbed at 250 degrees C for 4 min. Under the optimized
      conditions, 13 PAEs can be extracted completely and separated well. The limits of
      detection (LOD) were from 0.02 to 0. 83 microg/L (S/N = 3). The water samples
      collected from Baiyangdian lake were successfully analyzed using the proposed
      method, phthalic acid, bis-isobutyl ester (DIBP), phthalic acid, bis-butyl ester
      (DBP) and phthalic acid, bis-2-ethylhexyl ester (DEHP) were detected in all the
      samples. The spiked (2.5 microg/L and 5.0 microg/L) recoveries were in the range
      of 75.3-111.0% and the relative standard deviations (RSDs) were between 2.1% and
      8.0% (n=3). The results showed that this would be a valuable method for PAEs
      analysis in environmental water samples.

PMID- 20812633
TI  - [Development of standard gas mixture of chlorinated hydrocarbons in nitrogen].
AB  - A method for the preparation of the standard gas mixture of 6 chlorinated
      hydrocarbons, containing dichloromethane, 1,1-dichloroethane, 1,2-dichloroethane,
      chloroform, 1,1, 1-trichloroethane, and 1,1,2-trichloroethane, at the
      concentration of 5 micromol/mol in nitrogen was developed. The reproducibility of
      this method and the homogeneity and long-term stability of the standard mixture
      were evaluated. The results showed that all 6 chlorinated hydrocarbons have shown
      stability as long as 12 months and the expanded relative uncertainty of 5%. The
      certified value of developed standard gas agreed with the similar standard gas
      from Scott Specialty Gases. This research established a foundation for the
      analysis of volatile chlorinated hydrocarbon gases.

PMID- 20812634
TI  - [The research on a data fusion method of periodic-electrophysiology signal].
AB  - In this paper, onefold sensor is used to obtain periodic physiological signal,
      such as electrocardiogram signal. Multicycle data constitutes a sequence by the
      data of the corresponding time point. The data sequence, which is regard as a
      number of independent sensors data, is used to data fusion by one-dimensional
      method. This paper verifies the method by the measured ECG.

PMID- 20812635
TI  - [Colposcopy image database design and application of retrieval algorithm].
AB  - Due to the insufficiency in colposcopy image database collection in china, a
      novel image database is developed and it will be the basis of a computer-aided
      diagnosis system for colposcopy. An improved search algorithm of color is
      designed based on the current content-based image retrieval algorithms for the
      characteristics of colposcopy images. This algorithm is authenticated by more
      than one hundred of clinical pictures with primary satisfactory result.

PMID- 20812636
TI  - [Development and application of bioelectric measurement system for vivo bone
      puncture].
AB  - Procedure of a bioelectric signal collection system for vivo critter is
      introduced in this paper. It is easy to measure the bioimpedance in the tip of
      appliance, when puncture into the tissue, especially puncture into the bone
      tissue. We can get a judgment on the position of appliance, thereby achieve
      assistance on the clinic operation.

PMID- 20812637
TI  - [Mobile phone-computer wireless interactive graphics transmission technology and
      its medical application].
AB  - Application of clinical digital medical imaging has raised many tough issues to
      tackle, such as data storage, management, and information sharing. Here we
      investigated a mobile phone based medical image management system which is
      capable of achieving personal medical imaging information storage, management and
      comprehensive health information analysis. The technologies related to the
      management system spanning the wireless transmission technology, the technical
      capabilities of phone in mobile health care and management of mobile medical
      database were discussed. Taking medical infrared images transmission between
      phone and computer as an example, the working principle of the present system was
      demonstrated.

PMID- 20812638
TI  - [Measurement and analysis of phased-array focused ultrasound field of two-foci
      pattern].
AB  - This paper introduces the simulation and measurement results of the phased-array
      focused ultrasound field of two-foci pattern.

PMID- 20812639
TI  - [Numerical and experimental study of radial support capacity of intravascular
      stent].
AB  - The radial support capacity of intravascular stent is usually evaluated by the
      planar compression or the radial compression methods. Based on FEM simulation,
      the planer and radial compression methods are compared, and the agreement of the
      evaluation for the radial support capacity between these two methods is found.
      Moreover, the planer compression method is used to study the geometric
      parameters' effect on the radial support capacity by numerical simulations and
      experiments. Results show that, at the beginning of the compression process, the
      radial support capacity is mainly influenced by the metal-to-artery surface
      ratio; at large compression rate, the radial support capacity will decrease
      sharply with the increment of post-expansion diameter and decrement of the
      thickness and metal-to-artery surface ratio. The results provide guidance to the
      design and test of stents.

PMID- 20812640
TI  - [A new approach to research graphical performance of MRI RF coil based on the
      quantitative comparison method].
AB  - OBJECTIVE: To compare the performance of three different types of RF coil in 3.0T
      MRI, the signal-to-noise ratio (SNR) and image uniformity in 3.0 Tesla magnetic
      resonance imaging system have been studied. MATERIALS AND METHODS: In addition to
      the measurement of SNR and Uniformity based on the protocol recommend by AAPM,
      the images had also been analyzed using SPSS and MATLAB to get the SNR
      distribution along two vertical direction and the whole imaging plane. RESULTS:
      The SNR with T/R birdcage coil and 8-ch surface coil is seven and twelve times
      higher than surface coil in the region of interest (ROI), which was set in the
      center of the phantom images. With regard to the spatial variation of
      sensitivity, the uniformity of T/R birdcage coil and 8-ch surface coil are also
      much higher than that of surface coil. CONCLUSION: The images from T/R birdcage
      and phased array coils are all better than those of surface coil. The SNR of the
      images from phased array coil is highest while the uniformity of the images from
      T/R birdcage coil is highest.

PMID- 20812641
TI  - [A simulation system of otology microsurgery based on distributed virtual reality
      technology].
AB  - Traditionally, a novice ear doctor acquires the skillfully operative ability
      through dissecting cadaveric temporal bone in ear surgical training lab. For
      conceivable reasons donated bodies are always short in supply, virtual reality
      based simulator provides a new model for surgical training. It has been proven
      that the simulator is a useful tool for surgical training. And it can be used in
      the rehearsal of operation procedures, real-time operation guidance, and remote
      surgery. Our design is different from the existing virtual surgical system. It
      has a parallel, distributed multi-workstation with the vivid three-dimensional
      model of temporal bone, and it can be used not only to learn the ear surgical
      skills in the virtual environment, but also preoperative plan and surgical
      consultation.

PMID- 20812643
TI  - [On ambient experience medical products].
AB  - Through the analysis on ambient experience medical products from Philips
      corporation, the article discusses the development trend of medical products,
      management strategy and design thinking as focusing on advantage industry,
      focusing on user experience, system integration of resources and opening and
      diverse design thinking.

PMID- 20812642
TI  - [The development of hospital medical supplies information management system].
AB  - OBJECTIVE: The information management of medical materials by using high-tech
      computer, in order to improve the efficiency of the consumption of medical
      supplies, hospital supplies and develop a new technology way to manage the
      hospital and material support. METHODS: Using C # NET, JAVA techniques to develop
      procedures for the establishment of hospital material management information
      system, set the various management modules, production of various statistical
      reports, standard operating procedures. CONSEQUENCE: The system is convenient,
      functional and strong, fluent statistical functions. It can always fully grasp
      and understand the whole hospital supplies run dynamic information, as a modern
      and effective tool for hospital materials management.

PMID- 20812644
TI  - [Development of mobile MRI system].
AB  - This paper describes the development of mobile MRI system. The system technical
      solution, some calculation and test results are introduced, the technical
      characteristics are analysed, the same performance has been realized with an MRI
      system equipped in a vehicle, the market of original fixed MRI system has been
      extended.

PMID- 20812645
TI  - [Design of an microwave applicator using for tumor in superficial layer].
AB  - OBJECTIVE: A 2.45 GHz microstrip applicator using single rectangle sheet
      structure is presented. METHODS: Based on the radiant principle of microstrip
      antenna, the applicator's parameter is designed and the simulating model is set
      and optimized in HFSS. RESULTS: Measured by network analyzer, the technical
      target of this applicator is complied with design demand. During irradiation
      experiment, based on 30 W power, 30 mm radiation distance and 15 min duration
      experiment condition, the thermal field distribution map of phantom is obtained
      from the far-infrared image instrument. The 3D map shows that the region of
      thermal field centre has small radius and deep heat penetration. CONCLUSION: The
      microwave energy from this applicator can reach the tumor in superficial layer
      without heat injuring normal tissue around it.

PMID- 20812646
TI  - [Development of the disposable cannula for endoscope].
AB  - To introduce a kind of disposable double-channel cannula made by silica gel which
      is used for proctosigmoidoscopy, in coordination with rigid-tubing endoscope.
      There are kinds of characters for this cannula: small caliber, no toxic side
      effect, high degree of comfort, user-friendly, low system cost., etc.

PMID- 20812647
TI  - [Development of an auto-retractable self-disable safety syringe with high
      stability].
AB  - An auto-retractable self-disable safety syringe is introduced. The product mainly
      consists of barrel, plunger hander, needle holder, spring and needle cap. After
      injection, the clasp on top of plunger hander will be jammed with the outshoot of
      needle holder, meanwhile, the plunger hander tip expands the stop structure and
      consequently the compression spring pulls the needle and needle holder back into
      plunger hander. The technical parameters of present syringe such as break force,
      needle holder push out force and plunger hander lock force are very stable while
      working. With simple structure, reasonable design, easy manufacture and assemble,
      this product can been widely used in relevant area.

PMID- 20812648
TI  - [Development of the controller for alternative nebulizer].
AB  - OBJECTIVE: To develop a nebulizer controller which can be used to control the
      ultrasonic nebulizer and spray atomizer which can optimize the working of the
      nebulizer in pulse way, in a purpose to save the medication and minimize the
      impact on the environment. METHODS: Design the controller by using SCM to adjust
      the frequency and duty factor of the nebulizer pulse. The output pulse of the
      controller can drive a relay or a electromagnetic valve to control the pulse work
      of the two kind of nebulizer. RESULTS: The controller can work in a pulse way,
      and patients can inhale in pace with the nebulizer. CONCLUSION: The controller
      can save the medication by 50%, and reduce the impact on the environment by 50%.

PMID- 20812649
TI  - [The design and configuration of integrated multifunctional first-aid apparatus
      box].
AB  - With clinical first-aid needs, it is necessary to develop and produce combined
      first-aid equipment box to meet needs of the battlefield and emergency treatment.
      The choice of medical devices should also be followed to change, so as to well
      realize the scene first aid and portable purpose, whose internal configuration of
      medical devices can also be set according to actual requirements and have met a
      case of multiple uses, to suit different applications require medical treatment.

PMID- 20812650
TI  - [Study on the function and influence of hi-tech on medical and health
      undertakings development in China].
AB  - The invention and use of science and technology have always been a double-edged
      sword. The paper analysed the function and influence of medical hi-tech on
      medical and health undertakings development in China, and gives opinions on how
      to treat medical hi-tech correctly, so as to provide reference for the use and
      supervision of medical hi-tech.

PMID- 20812651
TI  - [Residual voltage of terms and test method].
AB  - This paper describes 5 national standards related to the term on the residual
      voltage with different indicators. Compare the advantages and disadvantages of
      various test methods. Finally, give suggestions on improving the testing method.

PMID- 20812652
TI  - [Dosimetric verification of the intensity modulated radiation therapy].
AB  - OBJECTIVE: To research the method of dosimetric verification of the intensity
      modulated radiation therapy (IMRT). METHODS: The IMRT treatment plans were
      designed by Eclipse TPS and were implemented in Varian ClinacIX LA with 6MV X
      ray. The absolute point doses were measured using a PTW 0.6 cc ion chamber with
      UNIDOS E dosimeter and the planes dose distributions were measured using PTW 2D
      Array ion chamber in the phantom. RESULTS: The error between the measured dose
      and calculated dose in the interesting points was less than 3%. The points passed
      ratio was more than 90% in gamma analysis method (3 mm 13%) about the plane dose
      distribution verification. CONCLUSION: The method of dosimetric verification of
      IMRT is reliable and efficient in the implementation.

PMID- 20812653
TI  - [The effect of evidence-based evaluation and economic evaluation for price
      control of medical disposable materials].
AB  - Evidence-based evaluation and economic evaluation could be identical to the
      products which should be priced by bidding or which should be listed individually
      through evidence-based evaluation. Meanwhile, economic evaluation is helpful to
      price listing individual products in a reasonable range. It will be extremely
      grateful if all colleagues can be a part of the program and set up a standard
      pricing rationale in science.

PMID- 20812654
TI  - [Implementations of hospital medical equipments quality control system].
AB  - Medical equipment quality control is the core content of hospital management. It
      runs through the whole process of medical equipment management, including the
      purchase, the installation and acceptance, the use and maintenance, the
      abandonment. It is the absolute duty for a hospital to assure and control the
      quality of the equipment. This paper presents the establishment of medical
      equipment quality control system, as well as a detailed description and analysis
      in the implementation of this system. Finally, discuss a few experiences in the
      quality control work.

PMID- 20812655
TI  - [Basic research on digital logistic management of hospital].
AB  - This paper analyzes and explores the possibilities of digital information-based
      management realized by equipment department, general services department, supply
      room and other material flow departments in different hospitals in order to
      optimize the procedures of information-based asset management. There are various
      analytical methods of medical supplies business models, providing analytical data
      for correct decisions made by departments and leaders of hospital and the
      governing authorities.

PMID- 20812656
TI  - [Application of automatic identification technology to monitor the entire process
      of medical management].
AB  - With the development of the hospital information technology management, to
      improve the clinic service quality and reduce medical errors, automatic
      identification technology has been widely used in health care areas. This
      technology has been used in our hospital for patient identification, sample
      identification, drug identification and equipment identification. Combined with
      wireless networks, mobile terminals and middleware etc., making the whole process
      of clinic service closed-loop system. This application improves efficiency,
      reduces mistakes and puts whole clinical service management process under
      control.

PMID- 20812657
TI  - [Case study of detecting and maintenance of AB 7300PCR].
AB  - The AB 7300 Real-time PCR Systems in our hospital have been detected malfunction
      for three times in a short term. The detection indicated the major reason for the
      malfunction attributed to the fuse of the solder of the COVER at the same
      position with the serial number 4344490 D1. This article explicitly introduces
      how to detect and maintain this equipment. It serves as a good reference for
      colleagues. Meanwhile the author raises five issues for further exploration and
      discussion.

PMID- 20812658
TI  - [Consent and confidentiality in occupational health practice: balance between
      legal requirements and ethical values].
AB  - INTRODUCTION: The recently introduced Italian law on the protection of workers'
      health states that the occupational health physician (competent physician) is
      required to act according to the Code of Ethics of the International Commission
      on Occupational Health (ICOH). AIM: This paper aims at examining the articles of
      legislative decree 81/2008 dealing with informed consent and confidentiality
      compared with the corresponding points of the ICOH Ethics Code. RESULTS: Analysis
      of the relationship between articles 25 and 39 (informed consent) and 18, 20 and
      39 (confidentiality) of the decree shows that there are some points of
      disagreement between the legal requirements and the Code of Ethics, in particular
      concerning prescribed health surveillance, consent based on appropriate
      information (points 8, 10 and 12 of the Code) and some aspects of confidentiality
      (points 10, 20, 21, 22 and 23 of the Code). CONCLUSION: Although the competent
      physician is required to act according to the law, the decisional process could
      lead to a violation of workers' autonomy.

PMID- 20812659
TI  - [Well-being in call centres: a multidisciplinary approach to research and
      evaluation].
AB  - BACKGROUND: The topics of stress and well-being in call centres are the focus of
      many different disciplines. This article presents the definition and start-up
      phases of the "Well-being in Telecom Italia Call Centres" project, which was
      coordinated and supervised by an interdisciplinary scientific committee composed
      of members from different universities. To address the topic of individual well
      being in the organizational context means considering all the main factors that
      can affect wellbeing. OBJECTIVES: For this reason, the study assessed the topic
      from three different view-points (psychological/sociological/cultural,
      physical/chemical/biological, organizational/technological/work-related) in order
      to obtain an accurate as possible picture of the complex well-being dynamics.
      METHODS: The study plan shows that merging qualitative methods (interviews,
      observations, focus-groups) and quantitative methods (questionnaires,
      physiological response to perceived stress) was a central concern for the
      research team. RESULTS: The collected data highlighted important differences
      between psychological and physical well-being and discomfort according to the
      different kinds of call centre, the respondents'gender and working hours.
      CONCLUSIONS: This method enabled us to define the specific features of call
      centre environments, leading to a definition of work in the centres as an
      activity with high psychological uncertainty, where rigid rules coexist with
      demands of high levels of flexibility and competence, and suggesting the
      importance of specific organizational measures in order to improve well-being.

PMID- 20812660
TI  - [Cancer incidence among petrochemical workers in the Porto Torres industrial
      area, 1990-2006].
AB  - BACKGROUND: Various epidemiological studies explored cancer mortality and
      incidence among petrochemical workers. We followed up cancer incidence in a
      cohort of 5350 male petrochemical workers in the industrial area of Porto Torres
      (Sardinia, Italy). MATERIAL AND METHODS: The follow-up covered the period from
      01/01/1990, when completeness of the cohort was certain and reference rates by
      the local Cancer Registry became available, up to 31/12/2006. Cohort members were
      subjects employed for six months or more in one of the chemical plants of the
      industrial area, alive as at 01/01/1990. Overall, a total of 81,392 person-years
      at risk were accumulated. The standardized incidence ratio (sir), as the ratio of
      observed to expected events, and its 95% confidence interval (CI) were calculated
      for all cancers and selected cancer sites, in the total cohort and in sub-cohorts
      of workers in plants where exposure to chemical agents evaluated in the IARC
      Monographs might have occurred. RESULTS: An increase in risk for all cancers was
      observed in the total cohort (596 cases; sir = 1.09; 95% CI 1.00-1.18), and it
      was highest for non-Hodgkin lymphoma (NHL, 26 cases: sir = 1.78; 95% CI 1.22
      2.62). Risk for haemolymphatic cancer was highest in the sub-cohort of workers
      employed for 10 years or more, with a latency period of 20 years or longer, and
      among those employed in the manufacture and polymerization of vinyl chloride
      (VCM; all cancers, 51 cases: sir = 1.43; 95% CI 1.08-1.88; NHL, 4 cases:
      sir=4.06; 95% CI 1.64-10.0). Risk of haemolymphatic cancer was not significantly
      elevated in the sub-cohort potentially exposed to benzene. An excess risk of
      bladder cancer (RR = 1.46; 95% CI 1.09-1.96), but not of pleural cancer, was
      observed in the sub-cohort potentially exposed to asbestos. No significant
      increase in cancer risk was observed among workers potentially exposed to
      acrylonitrile, butadiene, or styrene. CONCLUSIONS: Our follow-up study of
      petrochemical workers showed an increase in risk for all cancers, and
      particularly NHL, apparently concentrated among workers potentially exposed to
      VCM

PMID- 20812661
TI  - [Lung asbestos fibre burden in textile workers with malignant mesothelioma].
AB  - BACKGROUND: Lung burden of amphibole fibres is a good biological index of
      occupational cumulative asbestos exposure. Malignant mesothelioma (MM) has been
      amply documented in textile industry workers, dealing either with mineral fibres
      or with vegetable and animal fibres. So far the concentration of asbestos fibres
      in lung tissue among textile workers has not been reported in Italy. We analysed
      asbestos burden in the lung tissue of eleven textile-workers with malignant
      mesothelioma, mainly employed in industries near Brescia, in the North of Italy.
      OBJECTIVES: To characterize lung asbestos concentration and fibre type retained
      in the lung of asbestos and non-asbestos textile workers. METHODS: Sample of lung
      parenchyma from necropsies and extrapleural pneumonectomy were collected, stored
      and analysed by scanning electron microscope, according to the methods
      recommended in the current scientific literature. Nine patients were interviewed
      directly for occupational history. RESULTS: Eleven cases of MM (10 primary
      pleural, 1 primary peritoneal) were collected, 9 women and 2 men, aged between 51
      and 87 years, 4 asbestos-textile workers and 7 non-asbestos textile workers. The
      highest values of asbestos fibres were detected in all the workers of the former
      group and in 3 non-asbestos workers (jute recycling employees), with
      concentrations between 9.1 and 397 million/g of dried lung tissue. The total
      fibre concentration in the other 4 non-asbestos textile workers (silk and cotton
      production workers) ranged from 0.33 to 1.2 million/g of dried lung tissue. In
      only one of these subjects, did lung amphibole burden exceed 1,000,000 amphibole
      fibres longer than 1 microm per g of dried tissue. Eight cases out of eleven,
      showed a higher concentration of amphiboles than chrysotile. We detected
      amphibole fibres in all the "non-asbestos" textile workers and for two of them a
      higher concentration of tremolite. CONCLUSION: i) Among textile workers using
      asbestos or jute recycling, the asbestos fibre burden is as high as that found in
      other high risk jobs (e.g. asbestos-cement workers); ii) among non-asbestos
      textile workers, employed in cotton and silk production, the fibre content in
      lung tissue was much lower and it was nonetheless above the occupational cut-off
      for one of them; iii) tremolite found in lung tissue of non-asbestos textile
      workers with MM could be a contaminant of chrysotile friction materials or
      originate, with other amphiboles, from some other source as yet to be
      investigated.

PMID- 20812662
TI  - [Health surveillance of truck drivers: it is not just a question of drugs.
      Description of a one-year experience].
AB  - BACKGROUND AND OBJECTIVES: The aim of this paper was to analyze the results of
      the first year of a study on truck drivers'safety and health. The project, which
      started in 2008, is promoted by EBITRAL (trade unions and business joint
      association) and carried out by Occupational Medicine Department of Ospedali
      Riuniti di Bergamo. The final objective is to improve health conditions of truck
      drivers, by defining appropriate health surveillance protocols in order to asses
      fitness for work and by promoting the application of healthy life-styles among
      the workers. The first step required the collection of bio-statistical data, in
      order to analyze prevalence and incidence of work-related diseases in the future.
      METHODS: In the first year, 226 truck drivers (mean age 42. 7years, SD 9.5; mean
      working seniority 26.8 years, SD 10.6) were evaluated via application of an
      experimental survey protocol: medical examination, questionnaires for the main
      risks (low back pain, alcohol and drug consumption, sleepiness, etc),
      instrumental and laboratory tests (ECG, eye test, audiometric test, blood test,
      urinary drugs test). RESULTS: We observed 11 work-related diseases: 8 cases of
      hearing loss caused by chronic exposure to noise and 3 cases of low back disk
      disease. In 22 cases (9.7%) it was necessary to apply some restrictions to the
      truck drivers' fitness for work, first of all because of cardiovascular diseases
      and musculoskeletal disorders. We also found 3 subjects with positive urinary
      drug test: 1 for cocaine, 1 for methadone, 1 for cannabis. With the application
      of the experimental survey protocol many unknown diseases were also diagnosed
      (cardiovascular diseases, arterial hypertension, diabetes mellitus, etc), which
      could have played a role in increasing accident risk or, without an appropriate
      therapy, in reducing workers' future fitness for work. DISCUSSION: This first
      year of experience made it possible to collect bio-statistical data on truck
      drivers' work-related diseases. As regards fitness for work, we observed that
      drug consumption is not the most relevant health problem to consider in order to
      improve truck drivers' safety and citizens' safety on the road.

PMID- 20812663
TI  - [Occupational exposure to blood and body fluids in a Department of
      Odontostomatologic Sciences: results of a ten-year surveillance study].
AB  - BACKGROUND: Evaluation of occupational exposures can assist with practice
      modifications, redesign of equipment, and targeted educational efforts.
      OBJECTIVES: The aim of this analysis was to identify trends that will aid in the
      prediction and prevention of accidents. METHODS: Our data were collected from
      1999 to 2008 during a surveillance programme of occupational exposure to blood or
      other potentially infectious materials in a middle Dental School by using a
      standard coded protocol. RESULTS: Altogether 51 exposures were reported. Of
      these, 45/51 (88%) were percutaneous and 6/51 (12%) were of the mucosa, involving
      a splash in the eye of dental care workers (DCW). Of these 22/51 (43%) occurred
      among dental students, 17/51 (33%) among DCWs attending master and doctorate
      courses, 11/51 (22%) among DCWs attending as tutors and visiting professors and
      1/51 (2%) among staff. Regarding the circumstances of the exposures, 37/51 (73%)
      and 14/51 (27%) of the accidents occurred respectively during and after the use
      of a device; of latter, 1/14 (7%) was connected with instrument cleaning and with
      laboratory activity, 10/14 (71%) occurred when a DCW collided with a sharp
      object, and 2/14 (4%) happened during other activities. The instrument and the
      body part most likely to be involved were needles and fingers. The overall
      exposure rate was 5.15 +/- 0.72 standard error per 10,000 patient procedures.
      CONCLUSIONS: Our results may serve as a benchmark that other Dental Schools could
      adopt to assess accident frequency.

PMID- 20812664
TI  - [Prevention and diagnosis of occupational diseases: collaboration between the
      University of Studies of Milan and the International Labor Organization (ILO)].

PMID- 20812665
TI  - Cartagena declaration on rural health in Latin America.

PMID- 20812666
TI  - Superhydrophobic aluminum alloy surfaces by a novel one-step process.
AB  - A simple one-step process has been developed to render aluminum alloy surfaces
      superhydrophobic by immersing the aluminum alloy substrates in a solution
      containing NaOH and fluoroalkyl-silane (FAS-17) molecules. Scanning electron
      microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and water contact angle
      measurements have been performed to characterize the morphological features,
      chemical composition and superhydrophobicity of the surfaces. The resulting
      surfaces provided a water contact angle as high as ~162 degrees  and a contact
      angle hysteresis as low as ~4 degrees . The study indicates that it is possible
      to fabricate superhydrophobic aluminum surfaces easily and effectively without
      involving the traditional two-step processes.

PMID- 20812667
TI  - Role of kinetic factors in chemical vapor deposition synthesis of uniform large
      area graphene using copper catalyst.
AB  - In this article, the role of kinetics, in particular, the pressure of the
      reaction chamber in the chemical vapor deposition (CVD) synthesis of graphene
      using low carbon solid solubility catalysts (Cu), on both the large area
      thickness uniformity and the defect density are presented. Although the
      thermodynamics of the synthesis system remains the same, based on whether the
      process is performed at atmospheric pressure (AP), low pressure (LP) (0.1-1 Torr)
      or under ultrahigh vacuum (UHV) conditions, the kinetics of the growth phenomenon
      are different, leading to a variation in the uniformity of the resulting graphene
      growth over large areas (wafer scale). The kinetic models for APCVD and LPCVD are
      discussed, thereby providing insight for understanding the differences between
      APCVD vs LPCVD/UHVCVD graphene syntheses. Interestingly, graphene syntheses using
      a Cu catalyst in APCVD processes at higher methane concentrations revealed that
      the growth is not self-limiting, which is in contrast to previous observations
      for the LPCVD case. Additionally, nanoribbons and nanostrips with widths ranging
      from 20 to 100 nm were also observed on the APCVD grown graphene. Interactions
      between graphene nanofeatures (edges, folds) and the contaminant metal
      nanoparticles from the Cu etchant were observed, suggesting that these samples
      could potentially be employed to investigate the chemical reactivity of single
      molecules, DNA, and nanoparticles with monolayer graphene.

PMID- 20812668
TI  - Room temperature palladium-catalyzed cross coupling of aryltrimethylammonium
      triflates with aryl Grignard reagents.
AB  - Aryltrimethylammonium triflates and tetrafluoroborates were found to be highly
      reactive electrophiles in the Pd-catalyzed cross coupling with aryl Grignard
      reagents. The coupling reactions proceed at ambient temperature with a nearly
      stoichiometric quantity of Grignard reagent, and diverse functionality is
      tolerated. Competition experiments established the reactivity of PhNMe(3)OTf
      relative to PhCl, PhBr, PhI, and PhOTf.

PMID- 20812669
TI  - Copper-catalyzed nitrogen loss of sulfonylhydrazones: a reductive strategy for
      the synthesis of sulfones from carbonyl compounds.
AB  - An efficient method for the synthesis of sulfones via nitrogen loss of sulfonyl
      hydrazones is described. The reaction was performed in the presence of simple
      copper salt and base by utilization of sulfonyl hydrazones, which were easily
      prepared from carbonyl compounds. A wide variety of aryl and alkyl sulfones were
      obtained in moderate to good yields.

PMID- 20812670
TI  - Bacterial community structure in geographically distributed biological wastewater
      treatment reactors.
AB  - Current knowledge of the microbial communities within biological wastewater
      treatment reactors is incomplete due to limitations of traditional culture-based
      techniques and despite the emergence of recently applied molecular techniques.
      Here we demonstrate the application of high-density microarrays targeting
      universal 16S rRNA genes to evaluate microbial community composition in five
      biological wastewater treatment reactors in China and the United States. Results
      suggest a surprisingly consistent composition of microbial community structure
      among all five reactors. All investigated communities contained a core of
      bacterial phyla (53-82% of 2119 taxa identified) with almost identical
      compositions (as determined by colinearity analysis). These core species were
      distributed widely in terms of abundance but their proportions were virtually the
      same in all samples. Proteobacteria was the largest phylum and Firmicutes,
      Actinobacteria, Bacteroidetes were the subdominant phyla. The diversity among the
      samples can be attributed solely to a group of operational taxonomic units (OTUs)
      that were detected only in specific samples. Typically, these organisms ranked
      somewhat lower in terms of abundance but a few were present is much higher
      proportions.

PMID- 20812671
TI  - Charge-selective Raman scattering and fluorescence quenching by "nanometal on
      semiconductor" substrates.
AB  - Ag nanoparticles synthesized on n and p-type Si were shown to exhibit charge
      selective surface-enhanced Raman scattering and fluorescence quenching. As
      revealed by electric force microscopy, the polarity and magnitude of the
      nanoparticle charge is controllable with the metal-semiconductor Fermi level
      difference and nanoparticle size. It is inferred that the Fermi level alignment
      is dominantly contributed by the charge-induced nanoparticle voltage.
      Nanoparticle charging also accounts for self-inhibition of coalescence during
      chemical reduction, allowing strong plasmon hybridization.

PMID- 20812672
TI  - Imidazole-catalyzed monoacylation of symmetrical diamines.
AB  - An imidazole-catalyzed protocol for monoacylation of symmetrical diamines has
      been developed. The protocol gave selective monoacylation of aliphatic (cyclic
      and acyclic) primary and secondary diamines. In the reaction, imidazole acts as
      both catalyst and a leaving group. Different monoacylated piperazines and other
      diamines were synthesized at room temperature in an ethanol/water solvent system.

PMID- 20812673
TI  - Investigation of the experimental limits of small-sample heteronuclear 2D NMR.
AB  - Practical experimental performance limits for an ensemble of heteronuclear 2D NMR
      experiments using a state-of-the-art 600 MHz 1.7 mm Bruker TCI Micro CryoProbe
      are reported. In the specific case of multiplicity-edited GHSQC, it was possible
      to acquire data on a 540 ng sample of strychnine (1; ~1.6 nmol), prepared by
      serial dilution, which was used as a model compound. The experiments discussed
      also included GCOSY, (13)C reference spectra, (1)H-(13)C GHMBC, IDR-GHSQC-TOCSY,
      1,1-ADEQUATE, and (1)H-(15)N GHMBC.

PMID- 20812674
TI  - Synthesis of inherently chiral azacalix[4]arenes and diazadioxacalix[4]arenes.
AB  - Described are nucleophilic aromatic substitution reactions for the synthesis of
      inherently chiral azacalix[4]arenes and diazadioxacalix[4]arenes comprised of two
      or three different aromatic monomers. A variety of functional groups are
      tolerated at the 2-, 4-, and 5-positions on the nucleophilic-component monomers;
      reactions are run under ambient atmosphere; and the macrocycles are constructed
      without isolation of intermediate linear species.

PMID- 20812675
TI  - Rapid formation of hindered cores using an oxidative Prins process.
AB  - An unprecedented oxidative Prins transformation on phenol derivatives mediated by
      a hypervalent iodine reagent has been developed. This method allows a rapid
      access to highly substituted compact systems present in several natural products
      via a carbon-based addition on an aromatic core. Substitution at each ring
      position has been demonstrated, enabling synthesis of molecules with up to two
      contiguous quaternary carbon centers in good yield.

PMID- 20812676
TI  - Nucleophilic scandium carbene complexes.
AB  - Using a geminal dianion as precursor, a nucleophilic scandium carbene complex (2)
      has been synthesized by salt metathesis on ScCl(3)(THF)(3) in 52% isolated yield.
      The X-ray structure as well as an NBO analysis points to a double interaction
      between the carbon and the scandium atoms. Quantification of the electron density
      donation from the carbon to the metal center, from both sigma and pi symmetry
      orbitals, predicts a "nucleophilic carbene" behavior. Addition of benzophenone on
      complex 2 results in the formation of the expected alkene derivative and the
      trapping of a rare, MU(3)-oxo-Sc species via a "scandia-Wittig" reaction.

PMID- 20812677
TI  - Chromatographic reduction of isobaric and isomeric complexity of fulvic acids to
      enable multistage tandem mass spectral characterization.
AB  - Humic substances and related material commonly grouped under the designation of
      natural organic matter (NOM) are of interest in fields ranging from marine
      chemistry and geochemistry to industry, agriculture, and pharmacology. High-field
      Fourier transform ion cyclotron resonance mass spectrometry enables resolution
      and identification of elemental compositions of up to thousands of components
      from a single mass spectrum. Here, we introduce an offline prefractionation to
      reduce the number of species of the same nominal (nearest-integer) mass, allowing
      for isolation of ions of one or a few m/z values, from which structural
      information can be obtained by low-resolution multistage tandem mass spectrometry
      (MS(n)). Alternatively, precharacterized fractions can be generated for other
      types of analysis. As an example, we demonstrate significant reduction of
      isomeric and isobaric complexity for Suwannee River fulvic acid (SRFA). The
      combined MS and MS(n) analyses support the hypothesis that early eluting material
      comprises older, highly oxidized SRFA, whereas later eluting material is younger,
      retaining some similarity with precursor material.

PMID- 20812678
TI  - Raman spectroscopic investigation of tetraethylammonium polybromides.
AB  - A large number of polyhalides, especially polyiodides, have been discovered and
      studied, but definitive studies on polybromides remain scarce. Br(3)(-) is the
      only monovalent polybromide with a known structure. Higher-order monovalent
      polybromide anions have been proposed but not structurally confirmed as discrete
      species. In this study tetraalkylammonium polybromides with molecular formulas
      R(4)NBr(2x+1) (R = ethyl; x = 1-4) were prepared by reacting tetraalkylammonium
      monobromide or tribromide salts with gas-phase bromine. Distinct and
      characteristic Raman spectra were obtained from the solid polybromides in the
      spectral range between 100 and 400 cm(-1). Experimental Raman spectra were
      compared to ab initio calculations to propose the structure of these polybromide
      anions. A general agreement between the experimental and theoretical results was
      observed. This study demonstrates that Raman spectroscopy is a sensitive
      technique for probing the structure of discrete monovalent polybromides.

PMID- 20812679
TI  - Attachment of calcium oxalate monohydrate crystals on patterned surfaces of
      proteins and lipid bilayers.
AB  - The attachment of calcium oxalate monohydrate (COM) crystals to renal tubules is
      thought to be one of the critical steps of kidney stone formation. Patterns of
      phosphatidylserine (DPPS) bilayers and osteopontin (OPN) were fabricated on
      silica substrates through the combination of a microcontact printing technique
      and fusion of lipid vesicles to create spatially organized surfaces of lipids and
      proteins that may mimic renal tubule surfaces while allowing direct visualization
      of the competition for COM attachment to compositionally different regions. In
      the case of DPPS-OPN patterns, micrometer-sized COM crystals dispersed in
      saturated aqueous calcium oxalate solutions attached preferentially to the OPN
      regions, in agreement with other in vitro studies that have suggested a binding
      affinity of OPN to COM crystal surfaces. COM crystals attached with nearly equal
      coverage to OPN and DPPS surfaces alone, suggesting that the preferential
      segregation of COM crystals to the OPN regions on the patterned surfaces reflects
      reversible attachment of micrometer-sized COM crystals capable of Brownian
      motion. These attached microcrystals then grow larger over time during immersion
      in the supersaturated calcium oxalate solutions. Free OPN, a major constituent in
      urine, adsorbs on COM crystals and suppresses attachment to DPPS, suggesting a
      link between OPN and reduced attachment of COM crystals to renal epithelium. This
      patterning protocol can be expanded to other urinary molecules, providing a
      convenient approach for understanding the effects of biomolecules on COM crystal
      attachment and the pathogenesis of kidney stones.

PMID- 20812680
TI  - Dinuclear copper(I) complexes containing cyclodiphosphazane derivatives and
      pyridyl ligands: synthesis, structural studies, and antiproliferative activity
      toward human cervical and breast cancer cells.
AB  - Several mixed-ligand copper(I) complexes of cyclodiphosphazanes,
      [(t)BuNP(NC(4)H(8)X)](2) (1, X = O; 2, X = NMe), were synthesized by reacting the
      octanuclear copper(I) complexes [Cu(8)(MU(2)-I)(8){[(t)BuNP(NC(4)H(8)X)](2)}(4)]
      (3, X = O; 4, X = NMe) with various pyridyl ligands. Interaction of the
      metallomacrocyclic complex 3 or 4 with pyridine, 2,2'-bipyridine, and 1,10
      phenanthroline afforded the neutral dinuclear complexes
      [(C(5)H(5)N)(4)Cu(2)I(2){[(t)BuNP(NC(4)H(8)X)](2)}] (5, X = O; 6, X = NMe),
      [(2,2'-bpy)(2)Cu(2)I(2){[(t)BuNP(NC(4)H(8)X)](2)}] (7, X = O; 8, X = NMe), and
      [(1,10-phen)(2)Cu(2)I(2){[(t)BuNP(NC(4)H(8)X)](2)}] (9, X = O; 10, X = NMe),
      respectively, in good yield. The new dinuclear complexes 3, 5, and 7-9 were
      tested for their cytotoxic properties against human cervical cancer (HeLa) cells.
      The results indicated that all of the copper complexes have in vitro antitumor
      activity either similar to or better than that of cisplatin, a widely used
      anticancer drug. Among the compounds tested, complex 9 showed the most potent
      inhibitory activity in HeLa cells. In addition, complex 9 was found to potently
      inhibit proliferation of human breast cancer cells (MCF-7), highly metastatic
      breast cancer cells (MDA-MB 231), and nontransformed Chinese hamster ovary (CHO)
      cells. Complex 9 inhibited proliferation of these cells in culture more potently
      than cisplatin; for example, complex 9 was found to inhibit proliferation of HeLa
      and MCF-7 cells 3 and 5 times more efficiently than cisplatin. Complex 9
      treatment damaged the DNA integrity, blocked the cells in the G1 phase of the
      cell cycle, and induced apoptosis via a p53-dependent pathway. The molecular
      structures of complexes 9 and 10 were confirmed by single-crystal X-ray
      diffraction studies.

PMID- 20812681
TI  - Synthesis and biochemical characterization of a series of 17alpha
      perfluoroalkylated estradiols as selective ligands for estrogen receptor alpha.
AB  - Despite intensive research efforts, the distinct biological roles of two closely
      related estrogen receptors, ERalpha and ERbeta, are only partially understood.
      Therefore, ligands selective for either of two isotypes are useful research tools
      because they allow for exerting a desired subset of biological effects mediated
      by only one of the receptors. Here we report on the synthesis of a new class of
      potent and selective ligands for ERalpha represented by a series of 17alpha
      substituted estradiols bearing lipophilic perfluoroalkyl chains. These 17alpha
      perfluoroalkylated estradiols were synthesized by Ru-catalyzed cross metathesis
      reactions of 17alpha-allyl- or 17alpha-vinylestradiols with
      perfluoroalkylpropenes. Compounds were tested in both agonistic and antagonistic
      modes using a panel of stable steroid receptor reporter cell lines established in
      U2OS cells and consisting of ERalpha-LBD, ERbeta-LBD, GR-LBD, and MR-LBD
      reporters. Some of the compounds are potent and selective agonists of ERalpha,
      exhibiting weak partial to no detectable agonistic activity on ERbeta. Notably,
      11c is the most ERalpha selective ligand of the prepared compounds because it
      activates ERalpha but inhibits ERbeta. In addition, some compounds are pure
      agonists on ERalpha but show mixed agonistic/antagonistic profile on ERbeta which
      is a typical pattern observed for selective estrogen receptor modulators (SERMs).

PMID- 20812682
TI  - Improvement in phosphorescence efficiency through tuning of coordination geometry
      of tridentate cyclometalated platinum(II) complexes.
AB  - A series of tridentate cyclometalated platinum(II) complexes (C(?)N*N)PtL (L = Cl
      or acetylide) featuring a fused five-six-membered metallacycle were synthesized.
      The structure of the complexes was confirmed by X-ray crystallography. In
      contrast to the C(?)N(?)N platinum complexes with a fused five-five-membered
      metallacycle, the platinum coordination in C(?)N*N complexes is much closer to a
      square planar geometry. The photophysical properties of the complexes were
      studied. The geometrical change from C(?)N(?)N to C(?)N*N led to a substantial
      improvement in phosphorescence efficiency of the complexes with an acetylide
      ligand in solution at room temperature. For example, the quantum yield of
      (C(?)N*N)PtCCPh was measured to be 56%, demonstrating a big jump from 4% reported
      for (C(?)N(?)N)PtCCPh.

PMID- 20812683
TI  - Total synthesis and absolute stereochemical assignment of (-)-communesin F.
AB  - A concise asymmetric total synthesis of (-)-communesin F (~6% overall yield in
      the longest linear sequence of 19 steps) is described. It features an
      unprecedented intramolecular oxidative coupling strategy for the elaboration of
      the requisite spiro-fused indoline moiety. Other notable elements are the use of
      TBS-protected (S)-phenylglycinol as a chiral auxiliary to induce the asymmetric
      formation of the spiro-fused indoline part, the mesylate-mediated formation of
      its G ring, and the introduction of the A ring at the final stage via
      intramolecular Staudinger reaction. This intramolecular Staudinger reaction
      proceeded smoothly at 80  degrees C, providing an additional example illustrating
      that twisted amides are more reactive than simple amides. Along with the total
      synthesis, we were able to assign the absolute configuration of natural
      communesin F as 6R,7R,8R,9S,11R.

PMID- 20812684
TI  - Rational design of FRET-based ratiometric chemosensors for in vitro and in cell
      fluorescence analyses of nucleoside polyphosphates.
AB  - Ratiometric fluorescence sensing is a useful technique for the precise and
      quantitative analysis of biological events occurring under complex conditions,
      such as those inside cells. We report herein the design of new ratiometric
      chemosensors for nucleoside polyphosphates such as ATP that are based on binding
      induced modulation of fluorescence resonance energy transfer (FRET) coupled with
      a turn-on fluorescence-sensing mechanism. We designed these new FRET-based
      ratiometric chemosensors by utilizing spectral overlap changes to modulate the
      FRET efficiency. Introduction of coumarin fluorophores as the FRET donors into a
      binuclear zinc complex as the FRET acceptor provided the ratiometric
      chemosensors. These chemosensors exhibited a clear dual-mission signal change
      upon binding with strong affinity (K(app) ~ 10(6)-10(7) M(-1)) to nucleoside
      polyphosphates in aqueous solution, whereas no detectable emission change was
      observed with monophosphates and phosphodiester species or various other anions.
      These chemosensors were used for real-time fluorescence monitoring of enzyme
      reactions such as saccharide synthesis by glycosyltransferase and phosphorylation
      by protein kinase, both of which involve nucleoside polyphosphates as substrates.
      The utility of ratiometric sensing by chemosensors was further demonstrated in a
      fluorescence-imaging study of the nucleoside polyphosphates inside living cells,
      wherein we ratiometrically visualized the stimulus-responsive concentration
      change of ATP, an indicator of the cellular energy level.

PMID- 20812685
TI  - Syntheses, structures, and magnetic properties of diphenoxo-bridged Cu(II)Ln(III)
      and Ni(II)(low-spin)Ln(III) compounds derived from a compartmental ligand (Ln =
      Ce-Yb).
AB  - Syntheses, characterization, and magnetic properties of a series of diphenoxo
      bridged discrete dinuclear M(II)Ln(III) complexes (M = Cu or Ni, Ln = Ce-Yb)
      derived from the compartmental Schiff base ligand, H(2)L, obtained on
      condensation of 3-ethoxysalicylaldehyde with trans-1,2-diaminocyclohexane, are
      described. Single crystal X-ray structures of eight Cu(II)Ln(III) compounds (Ln =
      Ce (1), Pr (2), Nd (3), Sm (4), Tb (7), Ho (9), Er (10), and Yb (12)) and three
      Ni(II)Ln(III) (Ln = Ce (13), Sm (16), and Gd (18)) compounds have been
      determined. Considering the previously reported structure of the Cu(II)Gd(III)
      (6) compound (Eur. J. Inorg. Chem. 2005, 1500), a total of twelve structures are
      discussed/compared in this study. Four types of composition are observed in the
      Cu(II)Ln(III) complexes: [Cu(II)LLn(III) (NO(3))(3)(H(2)O)] (1-3: Ln = Ce-Nd),
      [Cu(II)LSm(III)(NO(3))(3)].CH(3)COCH(3) (4), [Cu(II)(H(2)O)LLn(III)(NO(3))(3)]
      (5: Ln = Eu; 6: Ln = Gd), and [Cu(II)LLn(III)(NO(3))(3)] (4A: Ln = Sm; 7-12: Ln =
      Tb-Yb). On the other hand, the Ni(II)Ln(III) complexes are characterized to have
      two types of composition: [Ni(II)LLn(III)(H(2)O)(NO(3))(3)] (13-15: Ln = Ce-Nd)
      and [Ni(II)LLn(III)(NO(3))(3)].0.5CH(3)COCH(3) (16-24: Ln = Sm-Yb). Among twelve
      X-ray structures, seven belong to three different isomorphous sets (Cu(II)Ce(III)
      (1), Cu(II)Pr(III) (2), Cu(II)Nd(III) (3), and Ni(II)Ce(III) (13); Cu(II)Tb(III)
      (7), Cu(II)Ho(III) (9), Cu(II)Er(III) (10), and Cu(II)Yb(III) (12); Ni(II)Sm(III)
      (16) and Ni(II)Gd(III) (18)), whereas space group/unit cell parameters of two
      others (Cu(II)Sm(III) (4) and Cu(II)Gd(III) (6)) are of different types. The
      lanthanide(III) centers in Cu(II)Ce(III) (1), Cu(II)Pr(III) (2), Cu(II)Nd(III)
      (3), and Ni(II)Ce(III) (13) complexes are eleven-coordinated, while the
      lanthanide(III) centers in other compounds are ten-coordinated. As evidenced from
      the dihedral angle (delta) between the CuO(phenoxo)(2) and LnO(phenoxo)(2)
      planes, variation in the extent of planarity of the bridging moiety in the
      Cu(II)Ln(III) compounds takes place; the ranges of delta values are 0.8-6.2
      degrees  in the 4f(1-7) analogues and 17.6-19.1 degrees  in the 4f(8-13)
      analogues. The Cu(II)Gd(III) (6) compound exhibits ferromagnetic interaction
      (Eur. J. Inorg. Chem. 2005, 1500). The nature of the magnetic exchange
      interaction in the Cu(II)Ln(III) complexes has been understood by utilizing the
      empirical approach; the Ni(II)Ln(III) complexes have been used as references. The
      metal centers in the Eu(III) complex are uncorrelated, while other 4f(1-6)
      analogues (Ce(III), Pr(III), Nd(III), and Sm(III)) exhibit antiferromagnetic
      interaction. Among the higher analogues (4f(7-13)), only Yb(III) exhibits
      antiferromagnetic interaction, while interaction in other analogues (Gd(III),
      Tb(III), Dy(III), Ho(III), Er(III), and Tm(III)) is ferromagnetic. An important
      aspect of the present study is the measurement of the magnetic susceptibility of
      the unblocked samples as well as on blocking the samples with grease to avoid
      powder reorientation, if any. Comparison of the two sets of data reveals
      significant difference in some cases.

PMID- 20812686
TI  - Oligo(4-aminopiperidine-4-carboxylic acid): an unusual basic oligopeptide with an
      acid-induced helical conformation.
AB  - In sharp contrast with helical polypeptides carrying basic side chains, Api(8), a
      basic oligopeptide containing the non-natural achiral amino acid 4
      aminopiperidine-4-carboxylic acid (Api), adopts a helical conformation only in
      acidic media. Alkaline titration of a protonated Api(8) oligomer appended with a
      leucine derivative at its N-terminus showed that disruption of its helical
      conformation occurs in a pH range of 7-10. NMR studies indicated that the
      piperidine groups in Api(8), when nonprotonated, possibly interact with the
      proximal amide protons in the peptide backbone and hamper the formation of the H
      bonding network responsible for the helical conformation. The helical structure
      is induced not only by protonation but also by acylation of the piperidine
      groups.

PMID- 20812687
TI  - Surface-mediated two-dimensional growth of the pharmaceutical carbamazepine.
AB  - Scanning tunneling microscopy (STM) has become a staple surface microscopy
      technique for a number of research fields ranging from semiconductor research to
      heterogeneous catalysis. Pharmaceutical compounds, however, remain largely
      unstudied. Here we report the first STM study of carbamazepine (CBZ), an anti
      epileptic drug, on Au(111) and Cu(111) surfaces. The analysis reveals that CBZ
      adopts unusual chiral molecular architectures on both metals. These previously
      unreported structures, which are strikingly different from CBZ packing
      arrangements observed in 3D crystal structures, indicate that the main molecular
      architecture is driven by a combination of CBZ intermolecular hydrogen bonding
      and metal-CBZ interactions. Comparison of the 2D molecular structures reveals
      large differences in local geometry and packing density that are dependent on the
      nature of the metal surface. These results have implications for the potential
      role of metal surfaces as heteronuclei or templating agents for controlling
      polymorph formation, which continues to be a problem for many compounds in the
      pharmaceutical industry including CBZ.

PMID- 20812688
TI  - Comprehensive characterization of grafted expanded poly(tetrafluoroethylene) for
      medical applications.
AB  - Successful implantation of any biomaterial depends on its mechanical,
      architectural, and surface properties. Materials with good bulk properties seldom
      possess the appropriate surface characteristics required for good biointegration.
      The present study investigates the results of surface modification of a highly
      porous, fully fluorinated polymeric substrate, expanded poly(tetrafluoroethylene)
      (ePTFE), with a view to improving the surface bioactivity and hence ultimately
      its biointegration. Modification involved gamma irradiation-induced graft
      copolymerization with the monomers monoacryloxyethyl phosphate (MAEP) and
      methacryloxyethyl phosphate (MOEP) in various solvent systems (water, methanol,
      methyl ethyl ketone, and mixtures thereof). In order to determine the penetration
      depth of the graft copolymer into the pores and/or the bulk of the ePTFE
      membranes, angle-dependent X-ray photoelectron spectroscopy (XPS) and magnetic
      resonance imaging (MRI) were used. It was found that the penetration depth was
      critically affected by the choice of monomer and solvent as well as by the
      technique used to remove dissolved oxygen from the grafting mixture: nitrogen
      degassing versus vacuum. Difficulties due to the porous nature of the membranes
      in establishing the lateral position of the graft copolymers were largely
      overcome by combining data from microattenuated total reflectance Fourier
      transfer infrared (MU-ATR-FTIR) mapping and time-of-flight secondary ion mass
      spectrometry (ToF-SIMS) imaging. Results show that the large variation in graft
      heterogeneity found between different samples is largely an effect of the
      underlying substrate and choice of monomer. The results from this study provide
      the necessary knowledge and experimental data to control both the graft copolymer
      lateral position and depth of penetration in these porous ePTFE membranes.

PMID- 20812689
TI  - Electronic-structure-dependent bacterial cytotoxicity of single-walled carbon
      nanotubes.
AB  - Single-walled carbon nanotubes (SWNTs) have been previously observed to be strong
      antimicrobial agents, and SWNT coatings can significantly reduce biofilm
      formation. However, the SWNT antimicrobial mechanism is not fully understood.
      Previous studies on SWNT cytotoxicity have concluded that membrane stress (i.e.,
      direct SWNT-bacteria contact resulting in membrane perturbation and the release
      of intracellular contents) was the primary cause of cell death. Gene expression
      studies have indicated oxidative stress may be active, as well. Here, it is
      demonstrated for the first time how SWNT electronic structure (i.e., metallic
      versus semiconducting) is a key factor regulating SWNT antimicrobial activity.
      Experiments were performed with well-characterized SWNTs of similar length and
      diameter but varying fraction of metallic nanotubes. Loss of Escherichia coli
      viability was observed to increase with an increasing fraction of metallic SWNTs.
      Time-dependent cytotoxicity measurements indicated that in all cases the majority
      of the SWNT antimicrobial action occurs shortly after (<15 min) bacteria-SWNT
      contact. The SWNT toxicity mechanism was investigated by in vitro SWNT-mediated
      oxidation of glutathione, a common intracellular thiol that serves as an
      antioxidant and redox state mediator. The extent of glutathione oxidation was
      observed to increase with increasing fraction of metallic SWNTs, indicating an
      elevated role of oxidative stress. Scanning electron microscopy images of E. coli
      in contact with the SWNTs demonstrated electronic structure-dependent
      morphological changes consistent with cytotoxicity and glutathione oxidation
      results. A three-step SWNT antimicrobial mechanism is proposed involving (i)
      initial SWNT-bacteria contact, (ii) perturbation of the cell membrane, and (iii)
      electronic structure-dependent bacterial oxidation.

PMID- 20812690
TI  - Binding of ethanol on calcite: the role of the OH bond and its relevance to
      biomineralization.
AB  - The interaction of OH-containing compounds with calcite, CaCO(3), such as is
      required for the processes that control biomineralization, has been investigated
      in a low-water solution. We used ethanol (EtOH) as a simple, model, OH-containing
      organic compound, and observed the strength of its adsorption on calcite relative
      to OH from water and the consequences of the differences in interaction on
      crystal growth and dissolution. A combination of atomic force microscopy (AFM)
      and molecular dynamics (MD) simulations showed that EtOH attachment on calcite is
      stronger than HOH binding and that the first adsorbed layer of ethanol is highly
      ordered. The strong ordering of the ethanol molecules has important implications
      for mineral growth and dissolution because it produces a hydrophobic layer.
      Ethanol ordering is disturbed along steps and at defect sites, providing a bridge
      from the bulk solution to the surface. The strong influence of calcite in
      structuring ethanol extends further into the liquid than expected from electrical
      double-layer theory. This suggests that in fluids where water activity is low,
      such as in biological systems optimized for biomineralization, organic molecules
      can control ion transport to and from the mineral surface, confining it to
      specific locations, thus providing the organism with control for biomineral
      morphology.

PMID- 20812691
TI  - Theoretical investigation on the photophysical properties of model ruthenium
      complexes with diazabutadiene ligands [Ru(bpy)(3-x)(dab)(x)](2+) (x = 1-3).
AB  - In this study we report a theoretical comparative study of some photophysical
      properties in the [Ru(bpy)(3-x)(dab)(x)](2+) (x = 0-3) series. Density functional
      theory calculations, validated by highly correlated ab initio benchmark
      calculations, were used to investigate the absorption and emission properties of
      the complexes with x = 1-3. The presence of a 1,4-diaza-1,3-butadiene (dab)
      ligand dramatically changes these properties because of the strong pi-acceptor
      character of this ligand. As a result, comparing to the reference
      [Ru(bpy)(3)](2+) complex previously studied, we observed (i) a strong red-shift
      of the maximum of the absorption band, (ii) a strong decrease of the emission
      energy of the lowest triplet metal-to-ligand charge transfer state, with all the
      [Ru(bpy)(3-x)(dab)(x)](2+) (x = 1-3) complexes luminescent in the near-infrared
      region, while [Ru(bpy)(3)](2+) emits in the visible region, and (iii) the triplet
      metal-centered states become inaccessible in all the [Ru(bpy)(3-x)(dab)(x)](2+)
      (x = 1-3) complexes. Consequently, these complexes could be potential candidates
      for infrared light-emitting diodes and probes.

PMID- 20812692
TI  - Surface chemistry and spectroscopy of UG8 asphaltene Langmuir film, part 2.
AB  - While there has been much focus on asphaltenes in toluene, there has been much
      less focus on asphaltenes in other solvents. It is important to quantify
      characteristics of asphaltenes in solvents besides toluene in order to better
      assess their molecular architecture as well as their fundamental aggregation
      characteristics. The present work focuses on the investigation of UG8 asphaltene
      Langmuir films at the air-water interface using chloroform as spreading solvent.
      The results are compared to the results recently obtained using toluene as
      spreading solvent. Surface pressure-area isotherms and UV-vis spectroscopy
      indicate that asphaltenes form smaller nanoaggregates in chloroform than in
      toluene in similar concentration ranges. Still these nanoaggreates share common
      features with those in toluene. From the surface pressure-area and compression
      decompression isotherms, Brewster angle microscopy, and p-polarized infrared
      reflection-absorption spectroscopy, it was concluded that small size aggregates
      are spread on the water surface and the compression of the film leads to
      formation of large aggregates. The films (Langmuir-Schaefer and Langmuir
      Blodgett) studied by atomic force microscopy reveal the existence of
      nanoaggregates spread on the water surface that coexist with large aggregates
      formed during compression. In addition to these findings, the spreading solvent,
      chloroform, allows the determination of asphaltene absorption bands using in situ
      UV-vis spectroscopy at the air-water interface after 15 min waiting time period.
      The absorbance data carried out after waiting a time period of 1 h shows similar
      features with the ones carried out after only 15 min; therefore, there is no need
      to wait 1 h as in the case when toluene is used as spreading solvent. A
      comparison of the data obtained from chloroform and toluene shows that smaller
      aggregate sizes are obtained from chloroform as suggested from the surface
      pressure-area isotherm, in situ UV-vis spectroscopy, and atomic force microscopy.
      Nevertheless, the similarity of these nanoaggregates in different solvents
      suggests this formation is a fundamental property of asphaltenes. Moreover, the
      lack of the isolated absorption band for one-ring aromatics and only a small peak
      for two-ring aromatics in the UV spectrum of asphaltenes indicate that these
      groups are not present in asphaltenes in significant quantities.

PMID- 20812693
TI  - Self-assembly of thienylenevinylene molecular wires to semiconducting gels with
      doped metallic conductivity.
AB  - Oligo(thienylenevinylene) (OTV) based gelators with high conductivity are
      reported. When compared to OTV1, OTV2 having an increased conjugation length
      forms relatively strong gels with a metallic conductivity of 4.8 S/cm upon doping
      which is the highest value reported for an organogelator. This new class of
      conducting gels is expected to be useful for organic electronics and photonics
      application, particularly for bulk heterojunction devices.

PMID- 20812694
TI  - Monte Carlo optimization scheme to determine the physical properties of porous
      and nonporous solids.
AB  - A new method, based on a Monte Carlo scheme, is developed to determine physical
      properties of nonporous and porous solids. In the case of nonporous solids, we
      calculate the surface area. This surface area is found as the sum of areas of
      patches of different surface energy on the solid, which is assumed to take a
      patchwise topology (i.e., adsorption sites of the same energy are grouped
      together in one patch). As a result of this assumption, we derive not only the
      surface area, but also the accessible volume and the surface energy distribution.
      In the case of porous solids, the optimization method is used to derive the
      surface area and the pore size distribution simultaneously. The derivation of
      these physical properties is based on adsorption data from a volumetric
      apparatus. We test this novel idea with the inversion problem of deriving surface
      areas of patches of different energies for a number of nonporous solids. The
      method is also tested with the derivation of the pore size distribution of some
      porous solid models. The results are very encouraging and demonstrate the great
      potential of this method as an alternative to the usual deterministic
      optimization algorithms which are known to be sensitive to the choice of the
      initial guess of the parameters. Since the geometrical parameters are physical
      quantities (i.e., only positive values are accepted), we also propose a scheme to
      enforce the positivity constraint of the solution.

PMID- 20812695
TI  - Pickering emulsion templated layer-by-layer assembly for making microcapsules.
AB  - Pickering emulsions stabilized by poly(sodium styrenesulfonate) (PSS) surface
      modified LUDOX CL particles were used as templates for the layer-by-layer (LbL)
      deposition of polyelectrolytes and charged nanoparticles to form composite
      shells. The microcapsules resulting from repeated LbL coating with
      poly(diallyldimethylammonium chloride) (PDADMAC) and PSS had porous walls due to
      the loose arrangement of the original nanoparticle aggregates at the oil-water
      interface, leading to significant microcapsule rupture and low encapsulation
      efficiency. Microcapsules formed by coating with PDADMAC and anionic LUDOX HS
      nanoparticles led to dense walls and stronger microcapsules, suitable for
      microencapsulation of hydrophobic materials with a wide range of polarities.

PMID- 20812696
TI  - Organocatalytic and electrophilic approach to oxindoles with C3-quaternary
      stereocenters.
AB  - A Lewis base-catalyzed asymmetric allylic alkylation of Morita-Baylis-Hillman
      carbonates derived from isatins has been investigated, which provides an
      electrophilic pathway to access oxindoles bearing C3-quaternary stereocenters.
      Excellent diastereoselectivity and high enantioselectivity have been obtained in
      the vinylogous functionalization of alpha,alpha-dicyanoolefin nucleophiles,
      giving multifunctional products with vicinal quaternary and tertiary chiral
      carbon centers.

PMID- 20812697
TI  - cis-Dihydroxylation of alkenes with oxone catalyzed by iron complexes of a
      macrocyclic tetraaza ligand and reaction mechanism by ESI-MS spectrometry and DFT
      calculations.
AB  - [Fe(III)(L-N(4)Me(2))Cl(2)](+) (1, L-N(4)Me(2) = N,N'-dimethyl-2,11
      diaza[3.3](2,6)pyridinophane) is an active catalyst for cis-dihydroxylation of
      various types of alkenes with oxone at room temperature using limiting amounts of
      alkene substrates. In the presence of 0.7 or 3.5 mol % of 1, reactions of
      electron-rich alkenes, including cyclooctene, styrenes, and linear alkenes, with
      oxone (2 equiv) for 5 min resulted in up to >99% substrate conversion and
      afforded cis-diol products in up to 67% yield, with cis-diol/epoxide molar ratio
      of up to 16.8:1. For electron-deficient alkenes including alpha,beta-unsaturated
      esters and alpha,beta-unsaturated ketones, their reactions with oxone (2 equiv)
      catalyzed by 1 (3.5 mol %) for 5 min afforded cis-diols in up to 99% yield with
      up to >99% substrate conversion. A large-scale cis-dihydroxylation of methyl
      cinnamate (9.7 g) with oxone (1 equiv) afforded the cis-diol product (8.4 g) in
      84% yield with 85% substrate conversion. After catalysis, the L-N(4)Me(2) ligand
      released due to demetalation can be reused to react with newly added
      Fe(ClO(4))(2).4H(2)O to generate an iron catalyst in situ, which could be used to
      restart the catalytic alkene cis-dihydroxylation. Mechanistic studies by ESI-MS,
      isotope labeling studies, and DFT calculations on the 1-catalyzed cis
      dihydroxylation of dimethyl fumarate with oxone reveal possible involvement of
      cis-HO-Fe(V)?O and/or cis-O?Fe(V)?O species in the reaction; the cis
      dihydroxylation reactions involving cis-HO-Fe(V)?O and cis-O?Fe(V)?O species both
      proceed by a concerted but highly asynchronous mechanism, with that involving cis
      HO-Fe(V)?O being more favorable due to a smaller activation barrier.

PMID- 20812698
TI  - Dialkynyl carbene derivatives: generation and characterization of triplet tert
      butylpentadiynylidene (t-Bu-C=C-C-C=C-H) and dimethylpentadiynylidene (Me-C=C-C
      C=C-Me).
AB  - Triplet carbenes t-butylpentadiynylidene (t-BuC(5)H, 1a) and
      dimethylpentadiynylidene (MeC(5)Me, 1b) have been produced photochemically from
      their corresponding diazo compound precursors and studied spectroscopically in
      cryogenic matrices (N(2) or Ar) at 10 K. The infrared, electronic absorption, and
      electron paramagnetic resonance spectra of these species exhibit numerous
      similarities to the spectra of pentadiynylidene (HC(5)H) and
      methylpentadiynylidene (MeC(5)H) recorded previously. EPR spectra yield zero
      field splitting parameters that are typical for triplet carbenes with axial
      symmetry (t-BuC(5)H, 1a: |D/hc| = 0.61 cm(-1), |E/hc| ~ 0 cm(-1); MeC(5)Me, 1b:
      |D/hc| = 0.62 cm(-1), |E/hc| ~ 0 cm(-1)). Electronic spectra are characterized by
      weak absorptions (T(1) <- T(0)) in the near-UV and visible region (350-430 nm)
      with extended vibronic progressions. The electronic transitions of several -C(5)-
      carbenes are compared, and an apparent dependence of the transition wavelength on
      the level of alkyl substitution of the carbon chain is found. Chemical trapping
      of triplet 1a in an O(2)-doped matrix affords carbonyl oxides derived
      predominantly from attack at C-3. Both t-BuC(5)H (1a) and MeC(5)Me (1b) undergo
      photochemical rearrangement upon UV irradiation.

PMID- 20812699
TI  - Palladium-catalyzed [4 + 2] cycloaddition of o-(silylmethyl)benzyl esters with
      ketones: an equivalent to oxo-Diels-Alder reaction of o-xylylenes.
AB  - o-(Silylmethyl)benzyl carbonates reacted with various electron-deficient ketones
      in the presence of a palladium catalyst, affording the [4 + 2] cycloaddition
      products, isochromanes, in high yields. The palladium-catalyzed cycloaddition is
      equivalent to the oxo-Diels-Alder reaction of o-xylylene with ketones. The
      regioselectivities were extraordinarily affected by the structures of the o
      xylylene precursors and ketones. The unusual regiochemistry may support two
      competitive reaction pathways in the catalytic reaction.

PMID- 20812700
TI  - Seebeck tuning in chalcogenide nanoplate assemblies by nanoscale
      heterostructuring.
AB  - Chalcogenide nanostructures offer promise for obtaining nanomaterials with high
      electrical conductivity, low thermal conductivity, and high Seebeck coefficient.
      Here, we demonstrate a new approach of tuning the Seebeck coefficient of
      nanoplate assemblies of single-crystal pnictogen chalcogenides by
      heterostructuring the nanoplates with tellurium nanocrystals. We synthesized
      bismuth telluride and antimony telluride nanoplates decorated with tellurium
      nanorods and nanofins using a rapid, scalable, microwave-stimulated organic
      surfactant-directed technique. Heterostructuring permits two- to three-fold
      factorial tuning of the Seebeck coefficient, and yields a 40% higher value than
      the highest reported for bulk antimony telluride. Microscopy and spectroscopy
      analyses of the nanostructures suggest that Seebeck tunability arises from
      carrier-energy filtration effects at the Te-chalcogenide heterointerfaces. Our
      approach of heterostructuring nanoscale building blocks is attractive for
      realizing high figure-of-merit thermoelectric nanomaterials.

PMID- 20812701
TI  - Surface chemistry and spectroscopy of UG8 asphaltene Langmuir film, part 1.
AB  - This research focuses on a systematic investigation of UG8 asphaltene Langmuir
      films at the air-water interface using toluene as the spreading solvent. From the
      surface pressure-area isotherms, it was concluded that small-sized aggregates are
      spread on the water surface and the compression of the film leads to formation of
      large aggregates. Our methods provide a stringent test and confirmation for the
      formation of corresponding asphaltene nanoaggregates that have recently been
      proposed for bulk solutions. These results were confirmed by compression
      decompression isotherms, Brewster angle microscopy, and p-polarized infrared
      reflection-absorption spectroscopy. The transfer of a single layer using both the
      Langmuir-Schaefer and Langmuir-Blodgett deposition techniques shows different
      aggregate shapes depending on the technique used as imaged using atomic force
      microscopy. The films reveal the existence of nanoaggregates spread on the water
      surface that coexist with large aggregates formed during compression. For the
      nanoaggregate, the thickness of the Langmuir-Schaefer and Langmuir-Blodgett films
      determined by AFM is consistent with small aggregation numbers of nanoaggregates
      determined by Langmuir film compression. In addition to these findings, the
      spreading solvent, toluene, was found to be trapped within the aggregates as
      confirmed by in situ UV-vis spectroscopy at the air-water interface. This result
      was possible only after waiting a time period of 1 h to allow the complete
      evaporation of the spreading solvent. This is the only study that reveals the
      presence of the in situ toluene within the UG8 aggregates directly at the air
      water interface.

PMID- 20812702
TI  - Uranium pyrophosphate/methylenediphosphonate polyoxometalate cage clusters.
AB  - Despite potential applications in advanced nuclear energy systems, nanoscale
      control of uranium materials is in its infancy. In its hexavalent state, U occurs
      as (UO(2))(2+) uranyl ions that are coordinated by various ligands to give
      square, pentagonal, or hexagonal bipyramids. Creation and design of
      nanostructured uranyl materials requires interruption of the tendency of uranyl
      bipyramids to share equatorial edges to form infinite sheets that occur in
      extended structures. Where a bidentate peroxide group bridges uranyl bipyramids,
      the configuration is inherently bent, fostering formation of cage clusters. Here
      the bent configurations of four- and five-membered rings of uranyl peroxide
      hexagonal bipyramids are bridged by pyrophosphate or methylenediphosphonate,
      creating eight chemically complex cage clusters with specific topologies.
      Chemical complexity in such clusters provides opportunities for the tuning of
      cage sizes, pore sizes, and properties such as aqueous solubility. Several of
      these are topological derivatives of simpler clusters that contain only uranyl
      bipyramids, whereas others exhibit new topologies.

PMID- 20812703
TI  - Electrochemistry and electrogenerated chemiluminescence of
      dithienylbenzothiadiazole derivative. Differential reactivity of donor and
      acceptor groups and simulations of radical cation-anion and dication-radical
      anion annihilations.
AB  - We report here the electrochemistry and electrogenerated chemiluminescence (ECL)
      of a red-emitting dithienylbenzothiadiazole-based molecular fluorophore (4,7
      bis(4-(4-sec-butoxyphenyl)-5-(3,5-di(1-naphthyl)phenyl)thiophen-2-yl)-2,1,3
      benzothiadiazole, 1b). 1b contains two substituted thiophene groups as strong
      electron donors at the ends connected directly to a strong electron acceptor,
      2,1,3-benzothiadiazole, in the center. Each thiophene moiety is substituted in
      position 2 by 3,5-di(1-naphthyl)phenyl and in position 3 by 4-sec-butoxyphenyl.
      Cyclic voltammetry of 1b, with scan rate ranging from 0.05 to 0.75 V/s, shows a
      single one-electron reduction wave (E degrees (red) = -1.18 V vs SCE) and two
      nernstian one-electron oxidation waves (E degrees (1,ox) = 1.01 V, E degrees
      (2,ox) = 1.24 V vs SCE). Reduction of the unsubstituted 2,1,3-benzothiadiazole
      center shows nernstian behavior with E degrees (red) = -1.56 V vs SCE. By
      comparison to a digital simulation, the heterogeneous electron-transfer rate
      constant for reduction, k(r) degrees  = 1.5 * 10(-3) cm/s, is significantly
      smaller than those for the oxidations, k(o) degrees  > 0.1 cm/s, possibly
      indicating that the two substituted end groups have a blocking effect on the
      reduction of the benzothiadiazole center. The ECL spectrum, produced by electron
      transfer annihilation of the reduced and oxidized forms, consists of a single
      peak with maximum emission at about 635 nm, consistent with the fluorescence of
      the parent molecule. Relative ECL intensities with respect to 9,10
      diphenylanthracene are 330% and 470% for the radical anion-cation and radical
      anion-dication annihilation, respectively. Radical anion (A(-*))-cation (A(+*))
      annihilation produced by potential steps shows symmetric ECL transients during
      anodic and cathodic pulses, while for anion (A(-*))-dication (A(2+*))
      annihilation, transient ECL shows asymmetry in which the anodic pulse is narrower
      than the cathodic pulse. Digital simulation of the transient ECL experiments
      showed that the origin of the observed asymmetry is asymmetry in the amount of
      generated charges rather than instability of the electrogenerated species.

PMID- 20812705
TI  - Synthesis of simple diynals, diynones, their hydrazones, and diazo compounds:
      precursors to a family of dialkynyl carbenes (R(1)-C=C-C-C=C-R(2)).
AB  - A variety of substituted pentadiynols, -diynals, and -diynones have been prepared
      en route to precursors to dialkynyl carbenes (R(1)-C=C-C-C=C-R(2)). In light of
      the marginal stability associated with these simple systems, several strategies
      were required to assemble the carbon backbones. The requisite five-carbon
      skeletons were prepared using 4 + 1, 3 + 2, 2 + 2 + 1, and 2 + 1 + 1 + 1 coupling
      methodologies. The Dess-Martin periodinane serves as an excellent method for the
      oxidation of pentadiynols to diynals and diynones, although many of the oxidized
      products are sufficiently reactive that they were not isolated; rather, they were
      generated in situ and intercepted with nucleophiles such as tosylhydrazide or
      trisylhydrazide. The hydrazone derivatives are generally reliable precursors to
      diazo compounds and carbenes, although cyclization of the hydrazone to afford a
      pyrazole can be a complicating factor in certain instances.

PMID- 20812704
TI  - Structural basis for cyclic Py-Im polyamide allosteric inhibition of nuclear
      receptor binding.
AB  - Pyrrole-imidazole polyamides are a class of small molecules that can be
      programmed to bind a broad repertoire of DNA sequences, disrupt transcription
      factor-DNA interfaces, and modulate gene expression pathways in cell culture
      experiments. In this paper we describe a high-resolution X-ray crystal structure
      of a beta-amino turn-linked eight-ring cyclic Py-Im polyamide bound to the
      central six base pairs of the sequence d(5'-CCAGTACTGG-3')(2), revealing
      significant modulation of DNA shape. We compare the DNA structural perturbations
      induced by DNA-binding transcripton factors, androgen receptor and glucocorticoid
      receptor, in the major groove to those induced by cyclic polyamide binding in the
      minor groove. The cyclic polyamide is an allosteric modulator that perturbs the
      DNA structure in such a way that nuclear receptor protein binding is no longer
      compatible. This allosteric perturbation of the DNA helix provides a molecular
      basis for disruption of transcription factor-DNA interfaces by small molecules, a
      minimum step in chemical control of gene networks.

PMID- 20812706
TI  - New [2 * 2] copper(i) grids as anion receptors. Effect of ligand
      functionalization on the ability to host counteranions by hydrogen bonds.
AB  - Several complexes with a [2 * 2] grid structure have been obtained by the self
      assembly of different copper(I) salts and ligands of the type 4,6-bis(pyrazol-1
      yl)pyrimidine containing different substituents on the heterocycles. The main
      goal has been to evaluate the influence over the solid state and solution
      behavior of the functionalization of the pyrimidine ring with a primary amino
      substituent. The molecular and crystalline structures of some derivatives have
      been determined by X-ray diffraction. The grids contain two open voids formed by
      pairs of ligands facing one another on opposite sides of the grid in a somewhat
      divergent manner. One counteranion is hosted in each void interacting through
      hydrogen bonds and anion-pi interactions. The presence of the amino group that
      points toward the inside of the cavity dominates the interactions in the void and
      apparently determines the orientation of the hosted counteranion and that of the
      ligands. With the exception of the derivative with chloride as the anion, the
      grid structure is preserved in solution (NMR and UV-vis) and some cation-anion
      interaction, increased by the presence of the amino group, exists also in
      solution (DOSY experiments). The experiments of anion interchange performed in
      solution indicate that a higher stability is found for the host-guest aggregates
      with OTs(-) (p-Me-C(6)H(4)SO(3)) and NO(3)(-). While for these anions a 1:2
      stoichiometry is reached, for the rest of the anions tested (ReO(4)(-), OTf(-),
      and PF(6)(-)), only weaker 1:1 complexes are formed. Computational studies
      support the presence of anion-pi interactions.

PMID- 20812707
TI  - Dynamics of water filaments in disordered environments.
AB  - The formation, stability, and dynamics of water filaments in disordered
      environments is investigated by using atomistic molecular dynamics simulations.
      It is found that in an alkyl-chain arrangement representative of that used in
      liquid chromatography, extended water filaments can form for up to 1 ns before
      they are destroyed again due to thermal fluctuations. The water dynamics in the
      disordered stationary phase is surprisingly intense with about 10(7) per alkyl
      chain per second of water molecules flowing in and out of the stationary phase.
      This is compatible with estimates based on Fick's law using a homogeneous
      solubility-diffusion model. The simulations also establish the existence of
      different types of water molecules as was predicted 30 years ago. From the
      current simulations they can be identified as (SiOH-) surface-bound, interfacial,
      and bulk water molecules.

PMID- 20812708
TI  - Remarkable reactions and intermediates in titanocene(IV) chemistry: migratory
      insertion reactions of 2,2-disubstituted-1-alkenes, intramolecular 1,5-sigma bond
      metathesis via epsilon-agostic interactions, and a rare example of a beta-agostic
      alkyltitanocene complex.
AB  - The compound Cp(2)TiMe(2) reacts with [Ph(3)C][B(C(6)F(5))(4)] in CD(2)Cl(2) at
      205 K to give, inter alia, [Cp(2)TiMe(CD(2)Cl(2))][B(C(6)F(5))(4)]. This solvent
      separated ion pair reacts in turn with 2,4-dimethyl-1-pentene (DMP) to give a
      series of cationic species, the first being the alkene complex
      [Cp(2)TiMe(DMP)](+), which undergoes ready migratory insertion to form the sigma
      alkyl complex [Cp(2)Ti(CH(2)CMe(2)CH(2)CHMe(2))](+). The latter, which does not
      contain a beta-hydrogen atom, rearranges rapidly via an unprecedented 1,5-sigma
      bond metathesis reaction involving two isomeric epsilon-agostic species to give
      the sigma-alkyl species [Cp(2)Ti(CH(2)CHMeCH(2)CMe(3))](+); this does contain a
      beta-hydrogen atom and, in concurrent processes, eliminates H(2) or 2,4,4
      trimethyl-1-pentene (a major product) to form respectively the allylic complex
      [Cp(2)Ti{eta(3)-(CH(2))(2)CCH(2)CMe(3)}](+) (a major product) or the hydride
      complex [Cp(2)TiH](+). The latter reacts reversibly with free DMP to give the
      insertion product [Cp(2)Ti(CH(2)CHMeCH(2)CHMe(2))](+) (V, a major product), in
      which the italicized hydrogen atom engages in a beta-agostic interaction with the
      metal atom. Compound V is a rare example of both a beta-agostic derivative of a
      group 4 metallocene and a beta-agostic compound of any metal in which the (1)H
      resonance of the agostic hydrogen can be identified in the (1)H NMR spectrum
      (delta -3.43). Interestingly, a NOESY experiment on V indicates slow mutual
      exchange between the agostic hydrogen atom, the hydrogen atoms on C(1), and those
      of Me(2). These observations are consistent with the intermediacy of the allylic
      dihydrogen species [Cp(2)Ti(H(2)){eta(3)-(CH(2))(2)CCH(2)CHMe(2)}](+), which
      loses H(2) to form [Cp(2)Ti{eta(3)-(CH(2))(2)CCH(2)CHMe(2)}](+) (a minor
      product). Support for all steps of the proposed reaction scheme comes from
      product distributions, from labeling studies utilizing
      [Cp(2)Ti(CD(3))(CD(2)Cl(2))](+), and from extensive DFT calculations. The
      observed titanocene-based chemistry stands in stark contrast to that of the
      analogous zirconium system, in which the unusual but well-characterized cationic
      methyl alkene complex [Cp(2)ZrMe(DMP)](+) does not undergo migratory insertion
      and subsequent reactions.

PMID- 20812709
TI  - Resolving inhomogeneity using lifetime-weighted fluorescence correlation
      spectroscopy.
AB  - Fluorescence correlation spectroscopy (FCS) was extended by incorporating
      information of the fluorescence lifetime. This new experimental approach, called
      lifetime-weighted FCS, enables us to observe fluorescence lifetime fluctuations
      in the nano- to millisecond time region. The potential of this method for
      resolving inhomogeneity in complex systems was demonstrated. First, by measuring
      a mixture of two dye molecules having different fluorescence lifetimes, it was
      shown that the lifetime-weighted correlation deviates from the ordinary intensity
      correlation only when the system is inhomogeneous. This demonstrated that
      lifetime-weighted FCS is capable of detecting inhomogeneity in an ensemble
      averaged fluorescence decay profile without any a priori knowledge about the
      system. Second, we applied this method to a dye-labeled polypeptide, a
      prototypical model of complex biopolymers. It was found that the ratio between
      the lifetime-weighted and ordinary intensity correlation changes with change of
      the environment around the polypeptide. This result was interpreted in terms of
      environment-dependent conformational inhomogeneity of the polypeptide. Delay time
      dependence of the ratio was found to be constant from ~1 MUs to several
      milliseconds, indicating that the observed inhomogeneity is persistent in the
      measured time scale. In combination with fluorescence intensity correlation,
      lifetime-weighted FCS allows us to examine conformational fluctuations of complex
      systems in the time region from nano- to milliseconds, being free from the
      translational diffusion signal.

PMID- 20812710
TI  - Temperature-independent vibrational dynamics in an organic photovoltaic material.
AB  - Ultrafast orientational motion and spectral diffusion of the carbonyl stretch
      vibration of the functionalized fullerene, PCBM, blended with the conjugated
      polymer, CN-MEH-PPV, are examined with two-dimensional infrared and polarization
      resolved IR pump probe spectroscopy. In previous contributions from our group,
      the carbonyl stretch frequency of PCBM has been used as a local vibrational
      reporter to measure the temperature dependence of the time scale for dissociation
      of charge transfer excitons in CN-MEH-PPV:PCBM polymer blends. It was found that
      the rate of charge separation is independent of temperature, indicating that
      charge separation occurs through an activationless pathway. This assignment was
      supported by the observation at room temperature that thermal fluctuations do not
      give rise to spectral diffusion of the carbonyl stretch vibration on the
      picosecond and longer time scale. In this contribution, we examine the
      temperature dependence of the carbonyl vibrational dynamics to determine whether
      thermal fluctuations might give rise to spectral diffusion at other temperatures.
      We find that the time scale for fast wobbling-in-cone orientational motion is
      independent of temperature on the subpicosecond time scale. Similarly, spectral
      diffusion is not observed on the picosecond and longer time scale at all
      temperatures examined confirming our earlier interpretation of the frequency
      shift dynamics exclusively in terms of charge separation. Interestingly, the half
      angle characterizing the wobbling-in-cone orientational motion does increase at
      higher temperature due to increased free-volume resulting from thermal expansion
      of the polymer blend.

PMID- 20812711
TI  - A new strategy for the synthesis of poly-substituted 3-H, 3-fluoro, or 3
      trifluoromethyl pyridines via the tandem C-F bond cleavage protocol.
AB  - A new strategy for the synthesis of poly-substituted 3-H, 3-F, and 3
      trifluoromethyl pyridines based on C-F bond breaking of the anionically activated
      fluoroalkyl group is described. A series of 2,6-disubstituted 4-amino pyridines
      were prepared through this domino process in high yields under noble metal-free
      conditions, making this method a supplement to pyridine synthesis.

PMID- 20812712
TI  - Static and dynamic characterization of nanodiscs with apolipoprotein A-I and its
      model peptide.
AB  - The class A amphipathic alpha-helical peptide 18A is known to form discoidal
      phospholipid complexes (nanodiscs) similar to that formed by apolipoprotein A-I
      (apoA-I). To reveal the structural differences in nanodiscs formed with this
      protein and peptide, we prepared nanodiscs with 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine and applied fluorescence techniques to these nanoparticles.
      Fluorescence resonance energy transfer between 1,2-dioleoyl-sn-glycero-3
      phosphoethanolamine-N-(7-nitro-2-1,3-benzoxadiazol-4-yl) and 1,2-dioleoyl-sn
      glycero-3-phosphoethanolamine-N-(lissamine rhodamine B sulfonyl) in nanodiscs
      revealed that lipid exchange with 18A nanodiscs is mediated by collisions between
      nanodiscs. The fluorescence lifetime of dansyl phosphatidylethanolamine and
      excimer fluorescence of 1,2-bis(1-pyrenedecanoyl)-sn-glycero-3-phosphocholine
      showed that the degree of hydration of the membrane surface and lateral pressure
      of acyl chains in 18A nanodiscs are independent of the disc size, suggesting that
      18A nanodiscs form planar lipid bilayers irrespective of their size, which
      differs from apoA-I nanodiscs, whose bilayer deforms to a saddle surface with
      decreasing size. These results suggest that the flexible structure of a chain of
      helices in apoA-I is crucial for the formation of saddle surfaces in nanodiscs.

PMID- 20812713
TI  - Microwave-mediated synthesis of labeled nucleotides with utility in the synthesis
      of DNA probes.
AB  - A novel method of linking haptens to deoxycytidine 5'-triphosphate via microwave
      mediated bisulfate-catalyzed transamination with hydrazine has been developed.
      This method enables the tethering of small molecule haptens to dCTP via a
      discrete polyethylene glycol (PEG) spacer, yielding N(4)-aminodeoxycytidine 5'
      triphosphate-dPEG-haptens. This synthetic approach employs microwave-catalyzed
      hydrazinolysis that enables the attachment of spacers via hydrazine linkages. The
      microwave-mediated introduction of this hydrazine handle provides a significant
      improvement in yield over those of published thermal methods. The microwave
      reaction was shown to be scalable, and the final product was amenable to labeling
      with a wide variety of haptens. The resulting nucleotide triphosphates, N(4)
      aminodeoxycytidine 5'-triphosphate-dPEG-haptens, can serve as unique substrates
      for the enzyme-mediated labeling of DNA probes. The efficacy of incorporation of
      one such novel nucleotide, N(4)-aminodeoxycytidine 5'-triphosphate-dPEG(4)-DNP,
      has been demonstrated in nick translation labeling of HER2 and HPV probes. The
      labeled probes have been shown to be effective in visualizing their target genes
      in tissue.

PMID- 20812714
TI  - Colloid-facilitated transport of cesium in vadose-zone sediments: the importance
      of flow transients.
AB  - Colloid-sized particles are commonly detected in vadose-zone pore waters and are
      capable of binding chemicals with sorptive affinities for geologic materials.
      Published research demonstrates that colloids are capable of facilitating the
      transport of sorptive contaminants under conditions of steady pore water flow,
      when volumetric moisture content and pore water velocity are constant. Less is
      known about the role of colloids in governing contaminant mobility under
      transient-flow conditions, which are characteristic of natural vadose-zone
      environments. The objective of this study is to elucidate the influences of flow
      transients on the mobilization and transport of in situ colloids and colloid
      associated contaminants. We conducted column experiments in which the
      mobilization of in situ colloids and (137)Cs was induced by transients associated
      with the drainage and imbibition of (137)Cs contaminated-sediments. Our results
      demonstrate that substantial quantities of in situ colloids and colloid
      associated (137)Cs are mobilized as volumetric moisture content declines during
      porous-medium drainage and as volumetric moisture content increases during porous
      medium imbibition. We also find that the colloid-effect on (137)Cs transport is
      sensitive to changes in pore water ionic strength. That is, the quantities of
      colloids mobilized and the capacity of the these colloids to bind (137)Cs
      decrease with increasing ionic strength, leading to a decrease of the mass of
      (137)Cs eluted from the columns during porous-medium drainage and imbibition.

PMID- 20812715
TI  - Computational mutagenesis studies of hammerhead ribozyme catalysis.
AB  - Computational studies of the mutational effects at the C3, G8, and G5 positions
      of the hammerhead ribozyme (HHR) are reported, based on a series of twenty-four
      100-ns molecular dynamics simulations of the native and mutated HHR in the
      reactant state and in an activated precursor state (G8:2'OH deprotonated).
      Invoking the assumptions that G12 acts as the general base while the 2'OH of G8
      acts as a general acid, the simulations are able to explain the origins of
      experimentally observed mutational effects, including several that are not easily
      inferred from the crystal structure. Simulations suggest that the Watson-Crick
      base-pairing between G8 and C3, the hydrogen bond network between C17 and G5, and
      the base stacking interactions between G8 and C1.1, collectively, are key to
      maintaining an active site structure conducive for catalytic activity. Mutation
      induced disruption of any of these interactions will adversely affect activity.
      The simulation results predict that the C3U/G8D double mutant, where D is 2,6
      diaminopurine, will have a rescue effect relative to the corresponding single
      mutations. Two general conclusions about the simulations emerge from this work.
      First, mutation simulations may require 30 ns or more to suitably relax such that
      the mutational effects become apparent. Second, in some cases, it is necessary to
      look beyond the reactant state in order to interpret mutational effects in terms
      of catalytically active structure. The present simulation results lead to better
      understanding of the origin of experimental mutational effects and provide
      insight into the key conserved features necessary to maintain the integrity of
      the active site architecture.

PMID- 20812716
TI  - Synthesis of few-layer hexagonal boron nitride thin film by chemical vapor
      deposition.
AB  - In this contribution we demonstrate a method of synthesizing a hexagonal boron
      nitride (h-BN) thin film by ambient pressure chemical vapor deposition on
      polycrystalline Ni films. Depending on the growth conditions, the thickness of
      the obtained h-BN film is between ~5 and 50 nm. The h-BN grows continuously on
      the entire Ni surface and the region with uniform thickness can be up to 20 MUm
      in lateral size which is only limited by the size of the Ni single crystal
      grains. The hexagonal structure was confirmed by both electron and X-ray
      diffraction. X-ray photoelectron spectroscopy shows the B/N atomic ratio to be
      1:1.12. A large optical band gap (5.92 eV) was obtained from the photoabsorption
      spectra which suggest the potential usage of this h-BN film in optoelectronic
      devices.

PMID- 20812717
TI  - Twin-arginine translocation of methyl parathion hydrolase in Bacillus subtilis.
AB  - Secretion of recombinant enzymes to extracellular milieu is important for
      enhanced degradation of toxic pollutants since the substrates are often
      inadequately taken up by cells. The twin-arginine translocation (Tat) pathway is
      a secretion mechanism for the transport of folded proteins across the cytoplasmic
      membrane of bacteria. Notably, two substrate-specific Tat systems have previously
      been discovered in Bacillus subtilis. The uptake of organophosphates (OPs) is the
      rate-limiting factor in whole-cell degradation of OPs. In this study, to secret
      an OP-hydrolyzing enzyme, methyl parathion hydrolase (MPH), into the growth
      medium, the twin-arginine (RR-) signal peptide of trimethylamine N-oxide
      reductase (TorA) from Escherichia coli was used to target MPH to the Tat pathway
      of B. subtilis. Fractionation studies and MPH assays demonstrated that MPH was
      secreted into the culture supernatant where it was fully active. Export was fully
      blocked in a tat mutant, indicating that the observed export in wild-type cells
      was mediated exclusively by the Tat pathway. The amount of MPH present in the
      culture medium was estimated to be 6.1 mg/L. N-terminal sequencing of the
      purified MPH demonstrated that the TorA signal peptide had been processed
      correctly. The secretion of MPH neither inhibited cell growth nor affected cell
      viability. The recombinant strain showed the accelerated degradation for OPs and
      the culture supernatant effectively degraded OPs on vegetables. The recombinant
      strain may be ideal for large-scale production of MPH at low costs because of
      simplification of the protein purification step. The Tat pathway of B. subtilis
      was successfully utilized for extracellular secretion of MPH. This is the first
      demonstration of Tat-dependent export of an active heterologous protein in B.
      subtilis using an E. coli Tat signal peptide. This study highlights the potential
      of the B. subtilis Tat pathway for heterologous protein secretion.

PMID- 20812718
TI  - "Click" reaction in conjunction with diazeniumdiolate chemistry: developing high
      load nitric oxide donors.
AB  - The use of Cu(I)-catalyzed "click" reactions of alkyne-substituted
      diazeniumdiolate prodrugs with bis- and tetrakis-azido compounds is described.
      The "click" reaction for the bis-azide using CuSO(4)/Na-ascorbate predominantly
      gave the expected bis-triazole. However, CuI/diisopropylethylamine predominantly
      gave uncommon triazolo-triazole products as a result of oxidative coupling.
      Neither set of "click" conditions showed evidence of compromising the integrity
      of the diazeniumdiolate groups. The chemistry developed has applications in the
      synthesis of polyvalent and dendritic nitric oxide donors.

PMID- 20812719
TI  - Evaluation of bioaugmentation with entrapped degrading cells as a soil
      remediation technology.
AB  - Soil augmentation with microbial degraders immobilized on carriers is evaluated
      as a potential remediation technology using a mathematical model that includes
      degradation within spatially distributed carriers and diffusion or advection
      dispersion as contaminant mass transfer mechanisms. The total volume of carriers
      is a critical parameter affecting biodegradation performance. In the absence of
      advection, 320 and 20 000 days are required to mineralize 90% of the herbicide
      linuron by Variovorax sp. SRS16 encapsulated in 2 mm beads with 5 and 20 mm
      spacings, respectively. Given that many pesticide degraders have low intrinsic
      degradation rates and that only limited carrier to soil volume ratios are
      practically feasible, bioaugmented soils are characterized by low effective
      degradation rates and can be considered fully mixed. A simple exponential model
      is then sufficient to predict biodegradation as verified by comparisons with
      published experimental data. By contrast, the full spatially distributed model is
      needed to adequately model the degradation of faster degrading contaminants such
      as naphthalene and benzene which can be mass-transfer limited. Dimensionless
      Damkohler numbers are proposed to determine whether the spatially distributed
      model is required. Results show that field scale applications of immobilized
      degraders will be limited by the amount of carriers required to reach acceptable
      degradation rates.

PMID- 20812721
TI  - GREEN-MAC-LCCP: a tool for assessing the life cycle climate performance of MAC
      systems.
AB  - In 2008, 95% of the vehicle fleet in the developed countries and 80% of fleet in
      the developing countries were equipped with mobile air conditioning systems
      (MACs). Greenhouse gases (GHGs) are emitted due to refrigerant leakage (direct
      emissions) and due to the energy consumed by MACs operation (indirect emissions).
      In response to reducing the global warming impact of MACs, policy makers and the
      industry are investigating alternative refrigerant systems that use low global
      warming potential (GWP) refrigerants. The GREEN-MAC-LCCP model assesses the
      direct and indirect CO(2) equivalent emissions related to MACs usage, as well as
      those associated with the production, use and disposal of alternative
      refrigerants and MACs components. This model provides a platform for simple data
      input and provides an output summary as well as details that can be analyzed in a
      custom fashion by the user. It provides engineers and policy makers a state-of
      the-art tool, based on sound engineering data and methods, in order to facilitate
      the process of evaluating alternate refrigerants with low lifecycle global
      warming impact as well as providing the total impact of any MACs on the
      environment. It has been recognized as the standard of the MACs industry.

PMID- 20812720
TI  - Molecular basis of the selectivity of the immunoproteasome catalytic subunit LMP2
      specific inhibitor revealed by molecular modeling and dynamics simulations.
AB  - Given that immunoproteasome inhibitors are currently being developed for a
      variety of potent therapeutic purposes, the unique specificity of an alpha',beta'
      epoxyketone peptide (UK101) toward the LMP2 subunit of the immunoproteasome
      (analogous to beta5 subunit of the constitutive proteasome) has been investigated
      in this study for the first time by employing homology modeling, molecular
      docking, molecular dynamics simulation, and molecular mechanics Poisson-Boltzmann
      surface area (MM-PBSA) binding free energy calculations. On the basis of the
      simulated binding structures, the calculated binding free energies are in
      qualitative agreement with the corresponding experimental data, and the
      selectivity of UK101 is explained reasonably. The observed selectivity of UK101
      for the LMP2 subunit is rationalized by the requirement for both a linear
      hydrocarbon chain at the N terminus and a bulky group at the C terminus of the
      inhibitor, because the LMP2 subunit has a much more favorable hydrophobic pocket
      interacting with the linear hydrocarbon chain, and the bulky group at the C
      terminus has a steric clash with the Tyr 169 in beta5 subunit. Finally, our
      results help to clarify why UK101 is specific to the LMP2 subunit of
      immunoproteasome, and this investigation should be valuable for rational design
      of more potent LMP2-specific inhibitors.

PMID- 20812723
TI  - In vitro and in vivo trypanocidal evaluation of nickel complexes with an
      azapurine derivative against Trypanosoma cruzi.
AB  - Seven ternary nickel(II) complexes (three previously described and four firstly
      described here) with an azapurine derivative (the anionic form of 4,6-dimethyl
      1,2,3-triazolo[4,5-d]pyrimidin-5,7-dione) have been synthesized and
      spectroscopically characterized, and the crystal structures of three of them have
      been solved by X-ray diffraction. Studies in vitro and in vivo on the
      antiproliferative activity of these complexes against Trypanosoma cruzi
      (epimastigote, amastigote, and trypomastigote forms) have been carried out,
      displaying in some cases significantly higher antitrypanosomatid activity and
      lower toxicity than the reference drug for Chagas' disease, benznidazole (N
      benzyl-2-(2-nitro-1H-imidazol-1-yl)acetamide). Ultrastructural analysis and
      metabolism excretion studies were also executed in order to propose a possible
      mechanism of action for the assayed drugs.

PMID- 20812722
TI  - Stabilization of the bioactive pigment of opuntia fruits through maltodextrin
      encapsulation.
AB  - Betalains are water-soluble, nitrogen-containing pigments of growing interest in
      the food industry. They are present in most plants belonging to the order
      Caryophyllales, where they fulfill the role of anthocyanins, and are divided into
      two groups: violet betacyanins and yellow betaxanthins. They are bioactive
      molecules that account for health-promoting properties, recently described for
      cactus pears (Opuntia). In this work, the characteristic betalain of cactus
      pears, indicaxanthin, is obtained purely, and its stability is highly promoted by
      its encapsulation in a maltodextrin matrix. A suitable spray-drying procedure for
      encapsulation is described, and a bright yellow powder is obtained. The stability
      is analyzed under different conditions. In the absence of light, pure
      encapsulated pigment can be stored at 20  degrees C for months without
      appreciable loss of the bioactive substance and color variation. Furthermore,
      free radical scavenging and antioxidant properties of the pigment are studied
      under the ABTS(*+) radical and ferric reducing antioxidant power assays, in the
      presence and in the absence of maltodextrins. The stabilization of pure betalain
      pigments may boost the use of these bioactive and natural coloring molecules.

PMID- 20812724
TI  - Effect of disulfide interactions and hydrolysis on the thermal aggregation of
      beta-lactoglobulin.
AB  - The roles of sulfhydryl/disulfide interactions and acid/pepsin hydrolysis on beta
      lactoglobulin (beta-lg) thermal aggregation at acidic pH 3.35 and 2 were studied
      using rheology, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE), transmission electron microscopy (TEM), and Western blotting. Pepsin
      promoted additional hydrolysis compared to the acid-hydrolyzed control sample
      based on a 12% increase in free amino groups. Hydrolysis with pepsin also
      resulted in an increase in the apparent viscosity by 2 logs upon heating 8% beta
      lg solutions at pH 3.35. Seemingly, hydrolysis promoted thermal aggregation of
      beta-lg, correlating well with viscosity increases. Large microgels were observed
      in heated pepsin hydrolysates using TEM, supporting the increased viscosities of
      these dispersions. During thermal aggregation (85  degrees C, 3 h) of beta-lg at
      pH 3.35, beyond the existence of limited disulfide interactions, acid hydrolysis
      and noncovalent interactions more likely play a crucial role in defining the
      functionality of acidified powdered modified whey ingredients.

PMID- 20812726
TI  - Life cycle assessment: past, present, and future.
AB  - Environmental life cycle assessment (LCA) has developed fast over the last three
      decades. Whereas LCA developed from merely energy analysis to a comprehensive
      environmental burden analysis in the 1970s, full-fledged life cycle impact
      assessment and life cycle costing models were introduced in the 1980s and 1990 s,
      and social-LCA and particularly consequential LCA gained ground in the first
      decade of the 21st century. Many of the more recent developments were initiated
      to broaden traditional environmental LCA to a more comprehensive Life Cycle
      Sustainability Analysis (LCSA). Recently, a framework for LCSA was suggested
      linking life cycle sustainability questions to knowledge needed for addressing
      them, identifying available knowledge and related models, knowledge gaps, and
      defining research programs to fill these gaps. LCA is evolving into LCSA, which
      is a transdisciplinary integration framework of models rather than a model in
      itself. LCSA works with a plethora of disciplinary models and guides selecting
      the proper ones, given a specific sustainability question. Structuring,
      selecting, and making the plethora of disciplinary models practically available
      in relation to different types of life cycle sustainability questions is the main
      challenge.

PMID- 20812725
TI  - 1-Aryl-3-(1-acylpiperidin-4-yl)urea inhibitors of human and murine soluble
      epoxide hydrolase: structure-activity relationships, pharmacokinetics, and
      reduction of inflammatory pain.
AB  - 1,3-Disubstituted ureas possessing a piperidyl moiety have been synthesized to
      investigate their structure-activity relationships as inhibitors of the human and
      murine soluble epoxide hydrolase (sEH). Oral administration of 13 1-aryl-3-(1
      acylpiperidin-4-yl)urea inhibitors in mice revealed substantial improvements in
      pharmacokinetic parameters over previously reported 1-adamantylurea based
      inhibitors. For example, 1-(1-(cyclopropanecarbonyl)piperidin-4-yl)-3-(4
      (trifluoromethoxy)phenyl)urea (52) showed a 7-fold increase in potency, a 65-fold
      increase in C(max), and a 3300-fold increase in AUC over its adamantane analogue
      1-(1-adamantyl)-3-(1-propionylpiperidin-4-yl)urea (2). This novel sEH inhibitor
      showed a 1000-fold increase in potency when compared to morphine by reducing
      hyperalgesia as measured by mechanical withdrawal threshold using the in vivo
      carrageenan induced inflammatory pain model.

PMID- 20812727
TI  - Synthesis, structure-affinity relationships, and radiolabeling of selective high
      affinity 5-HT4 receptor ligands as prospective imaging probes for positron
      emission tomography.
AB  - In a search for high-affinity receptor ligands that might serve for development
      as radioligands for the imaging of brain 5-HT(4) receptors in vivo with positron
      emission tomography (PET), structural modifications were made to the high
      affinity 5-HT(4) antagonist (1-butylpiperidin-4-yl)methyl 8-amino-7-iodo-2,3
      dihydrobenzo[b][1,4]dioxine-5-carboxylate (1, SB 207710). These modifications
      were made mainly on the aryl side of the ester bond to permit possible rapid
      labeling of the carboxylic acid component with a positron emitter, either carbon
      11 (t(1/2) = 20.4 min) or fluorine-18 (t(1/2) = 109.7 min), and included (i)
      replacement of the iodine atom with a small substituent such as nitrile, methyl,
      or fluoro, (ii) methylation of the 8-amino group, (iii) opening of the dioxan
      ring, and (iv) alteration of the length of the N-alkyl goup. High-affinity
      ligands were discovered for recombinant human 5-HT(4) receptors with amenability
      to labeling with a positron emitter and potential for development as imaging
      probes. The ring-opened radioligand, (([methoxy-(11)C]1-butylpiperidin-4
      yl)methyl 4-amino-3-methoxybenzoate; [(11)C]13), showed an especially favorable
      array of properties for future evaluation as a PET radioligand for brain 5-HT(4)
      receptors.

PMID- 20812728
TI  - Improved cytochrome P450 3A4 molecular models accurately predict the Phe215
      requirement for raloxifene dehydrogenation selectivity.
AB  - The use of molecular modeling in conjunction with site-directed mutagenesis has
      been extensively used to study substrate orientation within cytochrome P450
      active sites and to identify potential residues involved in the positioning and
      catalytic mechanisms of these substrates. However, because docking studies
      utilize static models to simulate dynamic P450 enzymes, the effectiveness of
      these studies is strongly dependent on accurate enzyme models. This study
      employed a cytochrome P450 3A4 (CYP3A4) crystal structure (Protein Data Bank
      entry 1W0E) to predict the sites of metabolism of the known CYP3A4 substrate
      raloxifene. In addition, partial charges were incorporated into the P450 heme
      moiety to investigate the effect of the modified CYP3A4 model on metabolite
      prediction with the ligand docking program Autodock. Dehydrogenation of
      raloxifene to an electrophilic diquinone methide intermediate has been linked to
      the potent inactivation of CYP3A4. Active site residues involved in the
      positioning and/or catalysis of raloxifene supporting dehydrogenation were
      identified with the two models, and site-directed mutagenesis studies were
      conducted to validate the models. The addition of partial charges to the heme
      moiety improved the accuracy of the docking studies, increasing the number of
      conformations predicting dehydrogenation and facilitating the identification of
      substrate-active site residue interactions. On the basis of the improved model,
      the Phe215 residue was hypothesized to play an important role in orienting
      raloxifene for dehydrogenation through a combination of electrostatic and steric
      interactions. Substitution of this residue with glycine or glutamine
      significantly decreased dehydrogenation rates without concurrent changes in the
      rates of raloxifene oxygenation. Thus, the improved structural model predicted
      novel enzyme-substrate interactions that control the selective dehydrogenation of
      raloxifene to its protein-binding intermediate.

PMID- 20812729
TI  - Identification of selective norbornane-type aspartate analogue inhibitors of the
      glutamate transporter 1 (GLT-1) from the chemical universe generated database
      (GDB).
AB  - A variety of conformationally constrained aspartate and glutamate analogues
      inhibit the glutamate transporter 1 (GLT-1, also known as EAAT2). To expand the
      search for such analogues, a virtual library of aliphatic aspartate and glutamate
      analogues was generated starting from the chemical universe database GDB-11,
      which contains 26.4 million possible molecules up to 11 atoms of C, N, O, F,
      resulting in 101026 aspartate analogues and 151285 glutamate analogues. Virtual
      screening was realized by high-throughput docking to the glutamate binding site
      of the glutamate transporter homologue from Pyrococcus horikoshii (PDB code: 1XFH
      ) using Autodock. Norbornane-type aspartate analogues were selected from the top
      scoring virtual hits and synthesized. Testing and optimization led to the
      identification of (1R*,2R*,3S*,4R*,6R*)-2-amino-6-phenethyl-bicyclo[2.2.1]heptane
      2,3-dicarboxylic acid as a new inhibitor of GLT-1 with IC(50) = 1.4 MUM against
      GLT-1 and no inhibition of the related transporter EAAC1. The systematic
      diversification of known ligands by enumeration with help of GDB followed by
      virtual screening, synthesis, and testing as exemplified here provides a general
      strategy for drug discovery.

PMID- 20812730
TI  - Multimodal tumor-targeting peptides functionalized with both a radio- and a
      fluorescent label.
AB  - The use of monolabeled tumor-targeting peptides for molecular imaging is
      widespread. However, it is often desirable to use the same compound for different
      clinical applications, e.g., combined pre- and intraoperative tumor detection. On
      the basis of their detection sensitivity, the combination of radioactivity and
      fluorescence is probably the most valuable in multimodal molecular imaging. In
      this review, we compare multimodal peptide derivatives and discuss the influence
      of the diagnostic labels on receptor affinity and biodistribution. On the basis
      of the described constructs, we propose improvements for the design of future
      multimodal tumor-targeting peptide derivatives.

PMID- 20812731
TI  - Palladium-catalyzed modular assembly of electron-rich alkenes, dienes, trienes,
      and enynes from (E)-1,2-dichlorovinyl phenyl ether.
AB  - We have devised a modular construction of electron-rich alkene derivatives from
      trichloroethylene (TCE). The three C-Cl bonds of TCE have sufficiently different
      reactivities that they can be sequentially and selectively functionalized.
      Following the substitution of one chlorine by phenol to generate (E)-1,2
      dichlorovinyl ether, the C(1)-Cl group next participates in palladium-catalyzed
      cross-coupling reactions with a variety of organometallic reagents. Subsequently,
      the C(2)-Cl group can engage in cross-couplings, while the C(2)-H may be
      deprotonated and quenched with an electrophile. Thus, isomerically pure tri- and
      tetrasubstituted electron-rich alkenes may be accessed in as few as two steps
      from simple and inexpensive starting materials. This method is ideally suited for
      diversity-oriented synthesis of highly conjugated molecules of interest as
      chromophores or as potential molecular electronics. It also gives access to
      diverse building blocks for further synthetic elaboration into high-value
      compounds.

PMID- 20812732
TI  - Enantiopure trans-3-arylaziridine-2-carboxamides: preparation by bacterial
      hydrolysis and ring-openings toward enantiopure, unnatural D-alpha-amino acids.
AB  - Several racemic trans-3-arylaziridine-2-carboxamides were prepared and then
      resolved by Rhodococcus rhodochrous IFO 15564-catalyzed hydrolysis. The resulting
      enantiopure (2R,3S)-3-arylaziridine-2-carboxamides are adequate substrates to
      undergo fully stereoselective nucleophilic ring-openings at the C-3 ring position
      to finally yield enantiopure, unnatural d-alpha-aminocarboxylic acids.
      Experimental evidence is provided that suggests the fate of the (2S,3R)-3
      arylaziridine-2-carboxylic acids concomitantly formed during the resolution
      processes. In this context, the similar bacterial resolution of racemic 1
      arylaziridine-2-carboxamides and -carbonitriles, previously investigated by our
      research group, has been partially re-examined.

PMID- 20812733
TI  - Applications of femtochemistry to proteomic and metabolomic analysis.
AB  - Femtosecond laser pulses have been widely used as a tool to study molecular
      ionization and fragmentation. This article bridges the application of femtosecond
      laser technology in early research focused on small isolated molecules with that
      in modern biological mass spectrometry for proteomics and metabolomic analysis on
      large (140+ atoms) biomolecules. The single-shot interaction of a femtosecond
      laser with neutral para-nitrotoluene (pNT) is investigated with time-of-flight
      mass spectrometry and compared with the ultrafast photodissociation of protonated
      pNT in an ion trap mass spectrometer accumulated over ~1000 pulses. The ion trap
      experiment is then extended to longer biomolecules. As demonstrated in the
      examples of vasopressin and tomatine, this novel ion activation method provides
      greater sequence coverage and nonstatistical fragmentation, leading to valuable
      information complementary to conventional methods for structural analysis.

PMID- 20812734
TI  - Proteomic analysis of PAXgene-fixed tissues.
AB  - Formalin fixation and paraffin embedding is the standard technique for preserving
      biological material for both storage and histological analysis. Although recent
      progress has been made in the molecular analysis of formalin-fixed, paraffin
      embedded (FFPE) tissues, proteomic applications are a special challenge due to
      the cross-linking property of formalin. Here we present the results of a new
      formalin-free tissue fixative, PAXgene, and demonstrate successful extraction of
      nondegraded and immunoreactive protein for subsequent standard protein assays,
      such as Western blot analysis and reverse-phase protein arrays. High amounts of
      protein can be obtained from PAXgene-fixed, paraffin-embedded (PFPE) mouse liver
      and human spleen, breast, duodenum, and stomach tissues, similar to frozen
      material. By Western blot analysis, we found that the detection of membrane,
      cytoplasmic, nuclear, and phosphorylated protein from PAXgene-fixed human tissue
      samples was comparable to cryopreserved samples. Furthermore, the distribution of
      protein in PAXgene-fixed human tissue specimens is adequate for matrix-assisted
      laser desorption/ionization (MALDI) imaging mass spectrometry for in situ
      proteomic analysis. Taken together, we demonstrate here that PAXgene has great
      potential to serve as a novel multimodal fixative for modern pathology, enabling
      extensive protein biomarker studies on clinical tissue samples.

PMID- 20812735
TI  - Synthesis of multicyclic beta-lactam derivatives via solid-phase-generated
      ketenes.

PMID- 20812736
TI  - Engineering the redox potential over a wide range within a new class of FeS
      proteins.
AB  - MitoNEET is a newly discovered mitochondrial protein and a target of the TZD
      class of antidiabetes drugs. MitoNEET is homodimeric with each protomer binding a
      [2Fe-2S] center through a rare 3-Cys and 1-His coordination geometry. Both the
      fold and the coordination of the [2Fe-2S] centers suggest that it could have
      novel properties compared to other known [2Fe-2S] proteins. We tested the
      robustness of mitoNEET to mutation and the range over which the redox potential
      (E(M)) could be tuned. We found that the protein could tolerate an array of
      mutations that modified the E(M) of the [2Fe-2S] center over a range of ~700 mV,
      which is the largest E(M) range engineered in an FeS protein and, importantly,
      spans the cellular redox range (+200 to -300 mV). These properties make mitoNEET
      potentially useful for both physiological studies and industrial applications as
      a stable, water-soluble, redox agent.

PMID- 20812737
TI  - A bacteriophage-based platform for rapid trace detection of proteases.
AB  - Sensitive, inexpensive, and rapid protease activity assays are of great merit for
      clinical diagnostics. Detection of protease-based toxins produced by Clostridium
      botulinum and Bacillus anthracis represents a particularly challenging task, as
      exceptional sensitivity is a prerequisite because of the extreme potency of the
      toxins. Here we present an inexpensive and sensitive assay platform for activity
      based protease quantification utilizing filamentous bacteriophage as an
      exponentially amplifiable reporter and its application to the detection of these
      bacterial toxins. The assay is based on specific cleavage of bacteriophage from a
      solid support and its subsequent quantification by means of infectivity or
      quantitative PCR. Detection of botulinum neurotoxin (BoNT) serotypes A and B and
      anthrax lethal factor in the picomolar range was demonstrated with a limit of
      detection of 2 pM for BoNT/A under optimized conditions.

PMID- 20812738
TI  - Germacrane-type sesquiterpenoids from the roots of Valeriana officinalis var.
      latifolia.
AB  - Eight new germacrane-type sesquiterpenoids, volvalerenals A-E (2-6) and
      volvalerenic acids A-C (7-9), along with four known compounds, were isolated from
      a chloroform extract of the roots of Valeriana officinalis var. latifolia. The
      structures and relative configurations of 2-9 were elucidated on the basis of
      spectroscopic data interpretation. The effects of all compounds isolated on
      acetylcholinesterase were evaluated.

PMID- 20812739
TI  - Phase transformation and crystal structure of La(2)Ni(7)H(x) studied by in situ X
      ray diffraction.
AB  - The phase transformation of La(2)Ni(7) during hydrogenation was investigated by
      in situ X-ray diffraction. We found two hydride phases, La(2)Ni(7)H(7.1) (phase
      I) and La(2)Ni(7)H(10.8) (phase II), during the first absorption cycle. The metal
      sublattice of phase I was orthorhombic (space group Pbcn) with lattice parameters
      a = 0.50128(6) nm, b = 0.8702(1) nm, and c = 3.0377(1) nm. The sublattice for
      phase II was monoclinic (space group C2/c) with lattice parameters a = 0.51641(9)
      nm, b = 0.8960(1) nm, c = 3.1289(1) nm, and beta = 90.17(1) degrees . The lattice
      parameter c increased with the hydrogen content, while a and b decreased in the
      formation of phase I from the alloy. Phase transformation from phase I to phase
      II was accompanied by isotropic expansion. The La(2)Ni(4) and LaNi(5) subunit
      expanded by 48.9% and 6.0% in volume, respectively, during hydrogenation to phase
      I. They expanded an additional 14% and 5.8%, respectively, in the formation of
      phase II. The obtained volume expansion suggested different hydrogen distribution
      in the La(2)Ni(4) and LaNi(5) subunit during hydrogenation.

PMID- 20812740
TI  - Isolation of putative biosynthetic intermediates of prenylated indole alkaloids
      from a thermophilic fungus Talaromyces thermophilus.
AB  - The putative key biosynthetic intermediates of prenylated indole alkaloids have
      long been proposed but never isolated. Two such alkaloids, named
      talathermophilins A and B (1 and 2), were isolated from a thermophilic fungus
      Talaromyces thermophilus strain YM1-3 and were identified by NMR and MS
      spectroscopic analyses. The ratio of 1 and 2 in the culture broths was
      unexpectedly rather constant (about 2:3), which even remained unchanged despite
      the addition of exogenous 1 or 2, suggesting that talathermophilins might be of
      special function for the extremophilic fungus.

PMID- 20812742
TI  - Graphene nanoribbon devices produced by oxidative unzipping of carbon nanotubes.
AB  - We demonstrate that graphene nanoribbons (GNRs), produced by the chemical
      unzipping of carbon nanotubes, can be conveniently used from solution to hand
      paint unidirectional arrays of GNRs atop silicon oxide. Through this simple
      alignment technique, numerous GNR-based devices, including field effect
      transistors, sensors, and memories can be easily fabricated on a single chip, and
      then used to generate statistically relevant device assessments. Such studies
      immediately give insights into, for example, multilayering properties on
      conductance, the profound effects that atmospheric adsorbates have upon the
      transfer characteristics of graphene, and other phenomena affecting the
      performance of GNR devices.

PMID- 20812741
TI  - Direct C-H arylation of electron-deficient heterocycles with arylboronic acids.
AB  - A direct arylation of a variety of electron-deficient heterocycles with
      arylboronic acids has been developed. This new reaction proceeds readily at room
      temperature using inexpensive reagents: catalytic silver(I) nitrate in the
      presence of persulfate co-oxidant. The scope with respect to heterocycle and
      boronic acid coupling partner is broad, and sensitive functional groups are
      tolerated. This method allows for rapid access to a variety of arylated
      heterocycles that would be more difficult to access with traditional methods.

PMID- 20812743
TI  - Synthesis, electronic structure, and reactivity of strained nickel-, palladium-,
      and platinum-bridged [1]ferrocenophanes.
AB  - The group 10 bis(phosphine)metalla[1]ferrocenophanes, [{Fe(eta(5)
      C(5)H(4))(2)}M(Pn-Bu(3))(2)] [M = Ni (4a), Pd (4b), and Pt (4c)], have been
      prepared by the reaction of Li(2)[Fe(eta(5)-C(5)H(4))(2)].tmeda (5, tmeda =
      N,N,N',N'-tetramethylethylenediamine) with trans-[MCl(2)(Pn-Bu(3))(2)] [M = Ni
      (trans-6a) and Pd (trans-6b)] and cis-[PtCl(2)(Pn-Bu(3))(2)] (cis-6c),
      respectively. Single crystal X-ray diffraction revealed highly tilted, strained
      structures as characterized by alpha angles of 28.4 degrees  (4a), 24.5 degrees 
      (4b), and 25.2 degrees  (4c) and a distorted square planar environment for the
      group 10 metal center. UV/visible spectroscopy and cyclic voltammetry indicated
      that all three compounds had smaller HOMO-LUMO gaps and were more electron-rich
      in nature than ferrocene and other comparable [1]ferrocenophanes. DFT
      calculations suggested that these differences were principally due to the
      electron-releasing nature of the M(Pn-Bu(3))(2) metal-ligand fragments. Attempts
      to induce thermal or anionic ring-opening polymerization of 4a-c were
      unsuccessful and were complicated by, for example, competing ligand dissociation
      processes or unfavorable chain propagation. In contrast, these species all
      reacted rapidly with acids effecting clean extrusion of the bis(phosphine)metal
      fragment. Carbon monoxide inserted cleanly into one of the palladium-carbon bonds
      of 4b to afford the ring-expanded, acylated product [{Fe(eta(5)-C(5)H(4))(eta(5)
      C(5)H(4))(CO)}Pd(Pn-Bu(3))(2)] (10). The nickel analogue 4a, however, afforded
      [Ni(CO)(2)(Pn-Bu(3))(2)] whereas the platinum-bridged complex 4c was inert.
      Remarkably, all compounds 4a-c were readily oxidized by elemental sulfur to
      afford the [5,5']bicyclopentadienylidene (pentafulvalene) complexes
      [{eta(4):eta(0)-C(5)H(4)(C(5)H(4))}M(Pn-Bu(3))(2)] [M = Ni (11a)] and [(eta(2)
      C(10)H(8))M(Pn-Bu(3))(2)] [M = Pd (11b) and Pt (11c)] by a formal 4-electron
      oxidation of the carbocyclic ligands. Compounds 11b and 11c represent the first
      examples of [5,5']bicyclopentadienylidene as a neutral eta(2)-ligand. The
      relative energies of eta(2)-coordination with respect to that of eta(4):eta(0)
      bonding were investigated for 11a-c by DFT calculations.

PMID- 20812744
TI  - Novel pathway to synthesize unsymmetrical 2,3,9,10,16,17,23-heptakis(alkoxyl)-24
      mono(dimethylaminoalkoxyl)phthalocyanines.
AB  - A new pathway by means of transetherification has been developed to synthesize
      novel unsymmetrical 2,3,9,10,16,17,23-heptakis(alkoxyl)-24
      mono(dimethylaminoalkoxyl)phthalocyanine compounds. Cyclic tetramerization of 4,5
      di(alkoxyl)phthalonitrile in refluxing dimethylamino-alcohol with high boiling
      point such as dimethylaminoethanol (DMAE) and 1-dimethylamino-2-propanol in the
      presence of lithium and pyrazino[2,3-f][1,10]phenanthroline-2,3-dicarbonitrile
      followed by treatment with acetic acid led to the isolation of a series of
      unsymmetrical metal free 2,3,9,10,16,17,23-heptakis(alkoxyl)-24
      mono(dimethylaminoalkoxyl)phthalocyanine compounds
      H(2){Pc(OR)(7)[OR'N(CH(3))(2)]} [R = C(4)H(9), C(5)H(11), C(8)H(17) and R' =
      C(2)H(4); R = C(4)H(9) and R' = CH(CH(3))CH(2)] (1-4). Metal insertion into
      unsymmetrical metal free phthalocyanines (Pc's) using Cu(OAc)(2).H(2)O in
      dimethylformamide (DMF) at 140  degrees C easily afforded corresponding
      unsymmetrical phthalocyaninato copper complexes Cu{Pc(OR)(7)[OR'N(CH(3))(2)]} (5
      8) in good yields. These novel unsymmetrical phthalocyanine compounds have been
      characterized by a series of spectroscopic methods including (1)H NMR, electronic
      absorption, IR, and mass spectroscopy in addition to elemental analysis. Their
      electrochemistry was also studied by cyclic voltammetry (CV) and differential
      pulse voltammetry (DPV) methods. The present result will be helpful for designing
      and preparing unsymmetrical phthalocyanines with potential applications in dye
      sensitized solar cells.

PMID- 20812745
TI  - Uncoupling nitrogenase: catalytic reduction of hydrazine to ammonia by a MoFe
      protein in the absence of Fe protein-ATP.
AB  - The catalytic reduction of hydrazine (N(2)H(4)) to ammonia by a beta-98(Tyr->His)
      MoFe protein in the absence of the Fe protein or ATP is reported. The reduction
      of N(2) or other substrates (e.g., hydrazine, protons, acetylene) by nitrogenase
      normally requires the transient association of the two nitrogenase component
      proteins, the Fe protein and the MoFe protein. The Fe protein, with two bound
      MgATP molecules, transfers one electron to the MoFe protein during each
      association, coupled to the hydrolysis of two MgATP. All substrate reduction
      reactions catalyzed by nitrogenase require delivery of electrons by the Fe
      protein coupled to the hydrolysis of MgATP. We report that when a single amino
      acid within the MoFe protein (beta-98(Tyr)) is substituted by His, the resulting
      MoFe protein supports catalytic reduction of the nitrogenous substrate hydrazine
      (N(2)H(4)) to two ammonia molecules when provided with a low potential reductant,
      polyaminocarboxylate ligated Eu(II) (E(m) -1.1 V vs NHE). The wild-type and a
      number of other MoFe proteins with amino acid substitutions do not show
      significant rates of hydrazine reduction under these conditions, whereas the beta
      98(His) MoFe protein catalyzes hydrazine reduction at rates up to 170 nmol
      NH(3)/min/mg MoFe protein. This rate of hydrazine reduction is 94% of the rate
      catalyzed by the beta-98(His) or wild-type MoFe protein when combined with the Fe
      protein, ATP, and reductant under comparable conditions. The beta-98(His) MoFe
      protein reduction of hydrazine in the absence of the Fe protein showed saturation
      kinetics for the concentration of reductant and substrate. The implications of
      these results in understanding the nitrogenase mechanism are discussed.

PMID- 20812746
TI  - Helical and flat structures from chiral dendronized rectangular oligo(phenylene
      ethynylene)s.
AB  - The synthesis of two chiral amphiphiles and their self-assembling features in
      solution and onto surfaces is reported. The different degree of interdigitation
      of the paraffinic substituents has an enormous influence in the chirality of the
      aggregates. Thus, while oligo(phenylene ethynylene) 1 shows a bisignated Cotton
      effect in solution and P-type helices onto surfaces, compound 2 lacks in any
      dichroic response at room temperature and self-assembles into flat ribbons.

PMID- 20812747
TI  - DFT study of bimetallic palladium-gold clusters Pd(n)Au(m) of low nuclearities (n
      + m <= 14).
AB  - Bimetallic palladium-gold Pd(n)Au(m) clusters of low nuclearity (n + m <= 14) are
      studied using the density functional theory at B3LYP level with a Lanl2DZ
      pseudopotential to understand the evolution of various structural, electronic,
      and energetic properties as a function of size (n + m) and composition (n/m) of
      the system. The potential energy surfaces have been explored for many different
      structures, and the minima obtained were then collected and used as a starting
      point for comparing the selected properties. Theoretical results show a logical
      evolution of the properties depending on the size and the composition of the
      system. Pd(n) clusters clearly prefer 3D structures while Au(m) clusters favor
      planar configurations. The geometry of the bimetallic Pd(n)Au(m) clusters mainly
      depends on their composition, i.e., clusters enriched in palladium atoms prefer
      3D structures while increasing gold contents promotes planar configurations with
      deviation from planarity near Pd centers. Regarding the electronic properties,
      NBO analysis reveals that the unique closed-shell electronic structure of Pd
      atoms (4d(10)) requires a (4d -> 5s) promotion to form stable bonds. In contrast,
      the half-occupied Au 6s AO implies effective Au-Au interaction and the electronic
      structure of Au atoms remains almost unchanged upon formation of bimetallic
      bonds. Consequently, clusters enriched in palladium atoms have spin
      multiplicities that increase with the cluster size while clusters enriched in
      gold atoms maintain the lowest possible spin multiplicity. Finally, the stability
      of these systems shows a synergic gain in cohesion for mixed Pd(n)Au(m) clusters
      compared to their monometallic Pd(n) and Au(m) counterparts. The maximal
      stabilization effect corresponds to n ~ m, compositions for which the number of
      mixed Pd-Au bonds is maximized.

PMID- 20812748
TI  - Improved LC-MS/MS spectral counting statistics by recovering low-scoring spectra
      matched to confidently identified peptide sequences.
AB  - Spectral counting has become a popular method for LC-MS/MS based proteome
      quantification; however, this methodology is often not reliable when proteins are
      identified by a small number of spectra. Here, we present a simple strategy to
      improve spectral counting based quantification for low-abundance proteins by
      recovering low-quality or low-scoring spectra for confidently identified
      peptides. In this approach, stringent data filtering criteria were initially
      applied to achieve confident peptide identifications with low false discovery
      rate (e.g., < 1% at peptide level) after LC-MS/MS analysis and database search by
      SEQUEST. Then, all low-scoring MS/MS spectra that matched to this set of
      confidently identified peptides were recovered, leading to more than 20% increase
      of total identified spectra. The validity of these recovered spectra was assessed
      by the parent ion mass measurement error distribution, retention time
      distribution, and by comparing the individual low score and high score spectra
      that correspond to the same peptides. The results support that the recovered low
      scoring spectra have similar confidence levels in peptide identifications as the
      spectra passing the initial stringent filter. The application of this strategy of
      recovering low-scoring spectra significantly improved the spectral count
      quantification statistics for low-abundance proteins, as illustrated in the
      identification of mouse brain region specific proteins.

PMID- 20812749
TI  - Structural diversity in supramolecular complexes of MCl(3) (M = As, Sb, Bi) with
      constrained thio- and seleno-ether ligands.
AB  - MCl(3) react with o-C(6)H(4)(EMe)(2) (E = S, Se) or o-C(6)H(4)(CH(2)ER)(2) (E =
      S, R = Me or Et; E = Se, R = Me) in anhydrous CH(2)Cl(2) or MeCN to give the
      yellow (Bi) or white (Sb) complexes, [MCl(3){o-C(6)H(4)(EMe)(2)}], [(MCl(3))(2){o
      C(6)H(4)(CH(2)SMe)(2)}(3)], [MCl(3){o-C(6)H(4)(CH(2)SEt)(2)}], and
      [(BiCl(3))(4){o-C(6)H(4)(CH(2)SeMe)(2)}(3)], which were characterized by
      IR/Raman, (1)H NMR spectroscopy, and microanalysis. The corresponding reactions
      with AsCl(3) gave oils. Using the tetrachalcogenoethers, 1,2,4,5
      C(6)H(2)(CH(2)EMe)(4) (E = S or Se), gave [(MCl(3))(2){1,2,4,5
      C(6)H(2)(CH(2)EMe)(4)}] (E = S: M = As, Sb or Bi; E = Se: M = As) as powdered
      solids. The structures adopted are extremely diverse within this related series.
      Crystal structure determinations show infinite chains for [MCl(3){o
      C(6)H(4)(EMe)(2)}] (M = Bi, E = S or Se; M = Sb, E = S), although the structures
      differ significantly in detail. [BiCl(3){o-C(6)H(4)(SMe)(2)}] is formed through
      chains of orthogonal MU-Bi(2)Cl(2) units linked together, with one dithioether
      ligand chelating per Bi atom, and seven-coordinate Bi; [SbCl(3){o
      C(6)H(4)(SMe)(2)}] comprises weakly associated Sb(2)Cl(6) dimer units linked into
      chains by weakly bridging dithioethers, where both available lone pairs on each S
      atom are used. [BiCl(3){o-C(6)H(4)(SeMe)(2)}] comprises distorted square
      pyramidal units involving pyramidal BiCl(3) primary coordination and a weakly
      chelating diselenoether ligand, and assembled into infinite chains through long
      bridging Bi...Cl interactions via all three Cl's. The 2:3 M:L complexes
      [(MCl(3))(2){o-C(6)H(4)(CH(2)SMe)(2)}(3)] (M = Bi or Sb) are isostructural, and
      also show one-dimensional polymers, but this time the coordination is based upon
      pyramidal MCl(3) units, with secondary bonding via three long M...S contacts from
      bridging dithioethers, and a further long M...Cl bridge which completes a
      distorted seven-coordinate environment at M. The Et-substituted thioether
      analogue gives the 1:1 [MCl(3){o-C(6)H(4)(CH(2)SEt)(2)}] for both Bi and Sb; the
      former showing a chain polymer structure based upon seven-coordinate Bi and
      bridging dithioethers and the latter a weakly Cl-bridged dimer with distorted
      octahedral coordination at Sb, with a chelating dithioether. The 4:3
      [(BiCl(3))(4){o-C(6)H(4)(CH(2)SeMe)(2)}(3)] complexes are based upon a central
      BiCl(6) octahedron linked to each of the other three Bi atoms via two bridging Cl
      atoms; the outer Bi atoms are also bonded to two mutually trans Se donor atoms
      from distinct diselenoethers, and two terminal Cl atoms, giving a distorted
      octahedral coordination environment at Bi. One of the two crystallographically
      independent tetrabismuth units is discrete, while the other shows further Cl
      bridges to adjacent units giving an infinite network. [(AsCl(3))(2){1,2,4,5
      C(6)H(2)(CH(2)SMe)(4)}] also forms an infinite network based upon square
      pyramidal As(III), and comprises pyramidal AsCl(3) units each weakly coordinated
      to two (mutually cis) S-donor atoms from two different thioether ligands. The Sb
      analogue is structurally very similar; however, in this case a solvent MeCN
      occupies the sixth coordination site. Finally, [(AsCl(3))(2){1,2,4,5
      C(6)H(2)(CH(2)SeMe)(4)}] forms an infinite chain based upon distorted octahedral
      coordination at As through three terminal (pyramidal) Cl atoms, two Se atoms from
      kappa(2)-MU(2)-selenoethers, although unexpectedly the chelation is through Se
      atoms that are mutually meta on the aromatic ring; with one Se atom on each
      ligand using both of its lone pairs to bridge (weakly) between two As atoms.
      These MCl(3)-chalcogenoether adducts are mostly weakly associated, and lead to
      very diverse structures which result from a combination of intra- and
      intermolecular interactions and crystal packing.

PMID- 20812750
TI  - Ring opening of a trisubstituted aziridine with amines: regio- and
      stereoselective formation of substituted 1,2-diamines.
AB  - The formation of substituted 1,2-diamines via nucleophilic ring opening of a
      trisubstituted ethynyl aziridine was performed with complete regio- and
      stereoselective control. Various amines with different levels of nucleophilicity
      were employed and gave similar results. The ring opening reaction is not limited
      to ethynyl aziridines, as other alkyl trisubstituted aziridines gave the same
      results. This method allows for the formation of unique vicinal diamines while
      providing a fully substituted carbon center in a stereoselective manner under
      mild conditions.

PMID- 20812751
TI  - A biomimetic total synthesis of (+)-ainsliadimer A.
AB  - A protecting group free and biomimetic total synthesis of (+)-ainsliadimer A has
      been accomplished in 14 steps from alpha-santonin. The synthesis relies on a
      hydrogen bonding promoted [4 + 2]-hetero-Diels-Alder dimerization to afford the
      key homodimer intermediate, which demonstrates the feasibility of using
      nonenzymatic conditions to achieve the proposed biosynthesis.

PMID- 20812752
TI  - The population of SAP and TSAP isomers in cyclen-based lanthanide(III) chelates
      is substantially affected by solvent.
AB  - The square antiprism/twisted square antiprism ratio in LnDOTA-tetraamide chelates
      is a critical parameter in governing water-exchange kinetics and ultimately the
      utility of a chelate as a PARACEST MRI contrast agent. In LnDOTA-tetraamide
      chelates with tertiary amides, this ratio and the rate of interconversion between
      these two structural isomers are found to be dramatically dependent upon the
      solvent and possibly other local environmental factors.

PMID- 20812753
TI  - Comparison of the structure and stability of new alpha-diimine complexes of
      copper(I) and silver(I): density functional theory versus experimental.
AB  - New compounds of the general formulas [M(Ar-BIAN)(2)]BF(4) and [M(Ar
      BIAN)(NCMe)(2)]BF(4), where M = Cu(I) or Ag(I) and Ar-BIAN =
      bis(aryl)acenaphthenequinonediimine, were synthesized by the direct reaction of
      [Cu(NCMe)(4)]BF(4) or [Ag(NCMe)(4)]BF(4) with the corresponding Ar-BIAN ligand in
      dried CH(2)Cl(2). The synthesized compounds are [M(o,o',p-Me(3)C(6)H(2)
      BIAN)(2)]BF(4) where M = Cu(I) (1) and Ag(I) (2), [M(o,o'-iPr(2)C(6)H(3)
      BIAN)(NCMe)(2)]BF(4) where M = Cu(I) (3) and Ag(I) (4), and [Ag(o,o'
      iPr(2)C(6)H(3)-BIAN)(2)]BF(4) (5). The crystal structures of compounds 1-3 and 5
      were solved by single-crystal X-ray diffraction. In all cases copper(I) or
      silver(I) are in a distorted tetrahedron that is constructed from the four
      nitrogen atoms of the two alpha-diimine ligands or, in 3, from one alpha-diimine
      ligand and two acetonitrile molecules. All compounds were characterized by
      elemental analyses, matrix-assisted laser desorption-ionization time-of-flight
      mass spectrometry, and IR, UV-vis, and (1)H NMR spectroscopy. The analysis of the
      molecular geometry and the energetic changes for the formation reactions of the
      complexes, in a CH(2)Cl(2) solution, were evaluated by density functional theory
      calculations and compared with the experimental results.

PMID- 20812754
TI  - Side reactions of nitroxide-mediated polymerization: N-O versus O-C cleavage of
      alkoxyamines.
AB  - Free energies for the homolysis of the NO-C and N-OC bonds were compared for a
      large number of alkoxyamines at 298 and 393 K, both in the gas phase and in
      toluene solution. On this basis, the scope of the N-OC homolysis side reaction in
      nitroxide-mediated polymerization was determined. It was found that the free
      energies of NO-C and N-OC homolysis are not correlated, with NO-C homolysis being
      more dependent upon the properties of the alkyl fragment and N-OC homolysis being
      more dependent upon the structure of the aminyl fragment. Acyclic alkoxyamines
      and those bearing the indoline functionality have lower free energies of N-OC
      homolysis than other cyclic alkoxyamines, with the five-membered pyrrolidine and
      isoindoline derivatives showing lower free energies than the six-membered
      piperidine derivatives. For most nitroxides, N-OC homolysis is normally favored
      above NO-C homolysis only when a heteroatom that is alpha to the NOC carbon
      center stabilizes the NO-C bond and/or the released alkyl radical is not
      sufficiently stabilized. As part of this work, accurate methods for the
      calculation of free energies for the homolysis of alkoxyamines were determined.
      Accurate thermodynamic parameters to within 4.5 kJ mol(-1) of experimental values
      were found using an ONIOM approximation to G3(MP2)-RAD combined with PCM
      solvation energies at the B3-LYP/6-31G(d) level.

PMID- 20812755
TI  - The molecularity of the Newman-Kwart rearrangement.
AB  - It was recently reported that the venerable Newman-Kwart rearrangement (1->2)
      proceeds via mixed first- and second-order kinetics. Prior to this, the
      rearrangement had been considered to proceed exclusively via an intramolecular
      O(Ar)->S(Ar) migration. A new bimolecular pathway, possibly involving an 8
      membered cyclic transition state, was proposed to account for reaction rates that
      increased disproportionately with substrate concentration under microwave heating
      conditions. We report a reanalysis of the kinetics and molecularity of the
      rearrangement of N,N-dimethyl O-(p-nitrophenyl)thiocarbamate 1a in N,N
      dimethylacetamide solvent. Using HPLC, isotopic labeling ((2)H, (18)O, (34)S),
      and ESI-ICRMS methods, we show that there is no evidence for a bimolecular
      pathway en route to 2a, with near-perfect exponential decay in 1a at
      concentrations ranging from 0.11 to 4.70 M. Instead, it is demonstrated that
      under the microwave heating conditions, a delayed negative feedback signal to the
      microwave power balancing loop results in oscillatory reaction overheating. Due
      to higher tan delta in the solute, the amplitude of this oscillation increases
      with the concentration of 1a, and this phenomenon best accounts for the kinetic
      behavior previously misinterpreted as being mixed first- and second-order in
      nature.

PMID- 20812756
TI  - A stereocontrolled synthesis of (+/-)-xenovenine via a scandium(III)-catalyzed
      internal aminodiene bicyclization terminated by a 2-(5-ethyl-2-thienyl)ethenyl
      group.
AB  - A highly diastereoselective binary hydroamination of a 5-amino-1,8-diene
      containing a 2-(5-ethyl-2-thienyl)ethenyl terminator has been utilized in an
      efficient synthesis of (+/-)-xenovenine (1). A pronounced rate enhancement was
      observed for cyclization onto the 2-(heteroaromatic)ethenyl group in comparison
      to a simple 1,2-disubstituted alkene.

PMID- 20812757
TI  - C3-symmetric cage-like receptors: chiral discrimination of alpha-chiral amines in
      a confined space.
AB  - Cage-like receptors that have internal binding sites and a C(3)-symmetric chiral
      bias have been synthesized, and their chiral discrimination behavior toward alpha
      chiral amines as their ammonium salts has been compared with that of their open
      structures.

PMID- 20812758
TI  - Enzymatic interconversion of ammonia and nitrite: the right tool for the job.
AB  - Hydroxylamine oxidoreductase (HAO) from Nitrosomonas europaea normally catalyzes
      oxidation of NH(2)OH to NO(2)(-). This paper reports experiments in which HAO was
      thermodynamically poised to catalyze reduction of NO(2)(-) to NH(4)(+). HAO was
      found to catalyze the reduction of NO(2)(-) by methyl viologen monocation radical
      (MV(red)), displaying a hyperbolic dependence on NO(2)(-) concentration, with a
      k(cat1) of 6.8 +/- 0.3 s(-1) and a K(m1) of 7.6 +/- 0.9 mM. HAO also catalyzed
      the reduction of NH(2)OH by MV(red), with a hyperbolic dependence on NH(2)OH
      concentration, and a k(cat2) of 245 +/- 3 s(-1) and a K(m2) of 6.8 +/- 0.2 mM
      (k(cat1) and k(cat2) reflect the maximum number of electrons transferred from
      MV(red) per second). We had previously demonstrated that HAO catalyzes the
      reduction of NO by MV(red) to yield first NH(2)OH and then NH(4)(+). Thus,
      overall, HAO is seen to act like a cytochrome c nitrite reductase, which
      catalyzes the six-electron reduction of NO(2)(-) to NH(4)(+) by MV(red). In the
      presence of Ru(NH(3))(2+) (Ru(II)) and Ru(NH(3))(3+) (Ru(III)) at ratios
      exceeding 200:1, HAO exhibited no detectable Ru(II)-NO(2)(-) oxidoreductase
      activity, though such activity is thermodynamically favored. On the other hand,
      HAO could still catalyze the oxidation of NH(2)OH to NO by Ru(III) under these
      conditions. The oxidative process exhibited a hyperbolic dependence on NH(2)OH
      concentration, with a k(cat3) of 98 +/- 3 s(-1) and a K(m3) of 5.2 +/- 0.8 MUM.
      Finally, HAO was found not to catalyze the disproportionation of NH(2)OH, despite
      the thermodynamic favorability of such a process, and the apparent opportunity
      presented by the HAO structure. Mechanisms are proposed to explain all the
      kinetic data.

PMID- 20812759
TI  - Characterization of the Human Adipocyte Proteome and Reproducibility of Protein
      Abundance by One-Dimensional Gel Electrophoresis and HPLC-ESI-MS/MS.
AB  - Abnormalities in adipocytes play an important role in various conditions,
      including the metabolic syndrome, type 2 diabetes mellitus and cardiovascular
      disease, but little is known about alterations at the protein level. We therefore
      sought to (1) comprehensively characterize the human adipocyte proteome for the
      first time and (2) demonstrate feasibility of measuring adipocyte protein
      abundances by one-dimensional SDS-PAGE and high performance liquid chromatography
      electron spray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS). In
      adipocytes isolated from approximately 0.5 g of subcutaneous abdominal adipose
      tissue of three healthy, lean subjects, we identified a total of 1493 proteins.
      Triplicate analysis indicated a 22.5% coefficient of variation of protein
      abundances. Proteins ranged from 5.8 to 629 kDa and included a large number of
      proteins involved in lipid metabolism, such as fatty acid transport, fatty acid
      oxidation, lipid storage, lipolysis, and lipid droplet maintenance. Furthermore,
      we found most glycolysis enzymes and numerous proteins associated with oxidative
      stress, protein synthesis and degradation as well as some adipokines. 22% of all
      proteins were of mitochondrial origin. These results provide the first detailed
      characterization of the human adipocyte proteome, suggest an important role of
      adipocyte mitochondria, and demonstrate feasibility of this approach to examine
      alterations of adipocyte protein abundances in human diseases.

PMID- 20812761
TI  - Human FEZ1 protein forms a disulfide bond mediated dimer: implications for cargo
      transport.
AB  - The human proteins FEZ1 (fasciculation and elongation protein zeta 1) and FEZ2
      are orthologs of the protein UNC-76 from C. elegans, involved in the growth and
      fasciculation of the worms axon. Pull down assays showed that the protein FEZ1
      interacts with other proteins (e.g., the protein SCOCO, short coiled-coil
      protein), mitochondria, and vesicles. These components may therefore represent
      cargoes to be transported along the microtubule, and the transport may be
      mediated through FEZ1 reported binding to kinesins (KIF3A). We previously showed
      that FEZ1 dimerizes in its N-terminal region and interacts with other proteins,
      including the candidate cargoe proteins, through its C-terminus. Here, we studied
      the fragment FEZ1(92-194) as well as full-length 6xHis-FEZ1 (1-392) in vitro and
      endogenous FEZ1 isolated from HEK 293 cells and were able to demonstrate the
      formation of an intermolecular disulfide bond through FEZ1 Cys-133, which appears
      to be essential for dimerization. This disulfide bond may be important for the
      FEZ1 role as a dimeric and bivalent transport adaptor molecule, since it
      establishes a strong link between the monomers, which could be a prerequisite for
      the simultaneous binding of two cargoes.

PMID- 20812760
TI  - Acetylation of RNA processing proteins and cell cycle proteins in mitosis.
AB  - Mitosis is a highly regulated process in which errors can lead to genomic
      instability, a hallmark of cancer. During this phase of the cell cycle,
      transcription is silent and RNA translation is inhibited. Thus, mitosis is
      largely driven by post-translational modification of proteins, including
      phosphorylation, methylation, ubiquitination, and sumoylation. Here, we show that
      protein acetylation is prevalent during mitosis. To identify proteins that are
      acetylated, we synchronized HeLa cells in early prometaphase and
      immunoprecipitated lysine-acetylated proteins with antiacetyl-lysine antibody.
      The immunoprecipitated proteins were identified by LC-ESI-MS/MS analysis. These
      include proteins involved in RNA translation, RNA processing, cell cycle
      regulation, transcription, chaperone function, DNA damage repair, metabolism,
      immune response, and cell structure. Immunoprecipitation followed by Western blot
      analyses confirmed that two RNA processing proteins, eIF4G and RNA helicase A,
      and several cell cycle proteins, including APC1, anillin, and NudC, were
      acetylated in mitosis. We further showed that acetylation of APC1 and NudC was
      enhanced by apicidin treatment, suggesting that their acetylation was regulated
      by histone deacetylase. Moreover, treating mitotic cells with apicidin or
      trichostatin A induced spindle abnormalities and cytokinesis failure. These
      studies suggest that protein acetylation/deacetylation is likely an important
      regulatory mechanism in mitosis.

PMID- 20812762
TI  - Analysis of nuclear high mobility group box 1 (HMGB1)-binding proteins in colon
      cancer cells: clustering with proteins involved in secretion and extranuclear
      function.
AB  - HMGB1 is a nuclear protein that is overexpressed and secreted in cancer cells.
      However, little is known about the roles of HMGB1 in the cytoplasm and secretory
      pathway in cancer cells. To clarify this aspect of HMGB1 function, we
      fractionated the cytoplasm of HCT116 colon cancer cells and used a proteomic
      approach to analyze cytoplasmic HMGB1-binding proteins. Pull-down experiments
      using recombinant HMGB1 protein as bait, followed by mass spectrometry analysis
      identified 162 interacting proteins. Among them were 74 proteins known to be
      localized exclusively to the extra-nuclear region, and 60 proteins known to be
      localized to both nuclear and extranuclear regions. The functions of these
      binding proteins include involvement in cell-cycle progression, cell
      proliferation, anti-apoptosis, and angiogenesis. In addition, nine of the
      identified proteins are related to protein translocation and secretion. These
      include annexin A2, myosin IC isoform a, myosin-9, and Ras-related protein Rab10,
      which are involved in unconventional protein secretion. Cytoplasmic HMGB1 was
      primarily associated with the lysosomal cytosol fraction and was colocalized with
      the lysosomal marker LAMP1. Our findings suggest that cytoplasmic HMGB1 binds to
      a number of molecules related to cancer progression and the unconventional
      secretory pathway.

PMID- 20812763
TI  - Cathepsin S mediates gastric cancer cell migration and invasion via a putative
      network of metastasis-associated proteins.
AB  - Cancer progression is governed by multifaceted interactions of cancer cells with
      their microenvironment and one of these ways is through secreted compounds.
      Substances released by gastric cancer cells have not being profiled in a proteome
      wide manner. ITRAQ-based tandem mass spectrometry was employed to quantify
      proteins secreted by HFE145 normal, MKN7 well-differentiated, and MKN45 poorly
      differentiated gastric cancer cell lines. The expression levels of 237 proteins
      were found to be significantly different between normal and cancer cells. Further
      examination of 16 gastric cell lines and 115 clinical samples validated the up
      regulation of CTSS expression in gastric cancer. Silencing CTSS expression
      suppressed the migration and invasion of gastric cancer cells in vitro.
      Subsequent secretomics revealed that CTSS silencing resulted in changes in
      expression levels of 197 proteins, one-third of which are implicated in cellular
      movement. Proteome-wide comparative secretomes of normal and gastric cancer cells
      were produced that constitute a useful resource for gastric cancer research. CTSS
      was demonstrated to play novel roles in gastric cancer cell migration and
      invasion, putatively via a network of proteins associated with cell migration,
      invasion, or metastasis. Cathepsin S is member of a large group of extracellular
      proteases, which are attractive drug targets. The implicated role of CTSS in
      gastric cancer metastasis provides an opportunity to test existing compounds
      against CTSS for adjuvant therapy and/or treatment of metastatic gastric cancers.

PMID- 20812764
TI  - Analysis of transcriptional factors and regulation networks in patients with
      acute renal allograft rejection.
AB  - Acute rejection (AR) remains a major clinical challenge, leading to the
      development of chronic renal allograft failure. The aim of the present study was
      to explore potential transcriptional factors and regulation networks in the
      disease to predict the occurrence and process of AR and understand potential
      strategies to prevent from the disease. Three-hundred fifty-two patients with
      renal failure had kidney transplantation during March 2006 and March 2010, of
      which 85 suffered from AR. Plasma from 13 patients with kidney transplantation
      was collected, of which 5 were from patients with AR and 8 from those without AR.
      Among the 179 proteins identified by using iTRAQ labeling and quantitative
      proteomic technology, 66 proteins were at least 2-fold different between patients
      with or without AR. The results demonstrated that the dominant processes and
      responses were associated with inflammation and complement activation in AR. A
      number of transcription factors were identified in AR patients, including nuclear
      factor-kappaB, signal transducer and activator of transcription 1, signal
      transducer and activator of transcription 3. The analysis of transcription
      regulation networks suggested that the cross-talks among these key transcription
      factors might contribute to the acute response and coagulation pathway. Thus, our
      study provides a new description and insight into the molecular events in AR and
      potential strategies for identifying diagnostic biomarkers.

PMID- 20812765
TI  - Contact dermatitis in older adults: a review of the literature.
AB  - Contact dermatitis is a significant health problem affecting the elderly.
      Impaired epidermal barrier function and delayed cutaneous recovery after insult
      enhances susceptibility to both irritants and allergens. Exposure to more
      numerous potential sensitizers and for greater durations influences the rate of
      allergic contact dermatitis in this population. Medical co-morbidities, including
      stasis dermatitis and venous ulcerations, further exacerbate this clinical
      picture. However, while these factors tend to increase the degree of
      sensitization in the elderly, waning immunity can actually decrease such a
      propensity. This interplay of both intrinsic and extrinsic factors makes a
      generalization on trends for contact dermatitis in older adults challenging. The
      literature has varying reports on the overall incidence of allergic contact
      dermatitis with advancing age. Nevertheless, it does clearly show that
      sensitivity to topical medicaments increases with age. Irritant contact
      dermatitis studies are more consistent, with less reactivity (to irritants) in
      older compared with younger skin. Diagnosis of both irritant and allergic contact
      dermatitis is based on a thorough history, complete skin examination, and
      comprehensive patch testing. The mainstay of therapy is avoidance of the
      offending chemical substances and the use of topical along with systemic
      therapies, depending on the severity of the condition.

PMID- 20812766
TI  - Reflections on attribution and decisions in pharmacovigilance.

PMID- 20812767
TI  - How to apply the human factor to periodic safety update reports.
AB  - Society has been increasingly intolerant of excuses for systems breakdown in many
      areas of public life. This is hardly surprising given that there is overwhelming
      evidence behind why processes fail and mistakes are made, and so, based on this
      evidence, processes should be designed to mitigate risk. The main root cause of
      many process failures can be attributed to the human factor, which encompasses
      all those factors that can influence people and their behaviour. Based on
      experience from other safety-conscious industries, there is a major move to
      manage the human factor as part of delivery of safety culture in healthcare
      systems. Since pharmaceutical companies are healthcare companies, it makes sense
      that the principles underlying a pharmaceutical safety culture are aligned with
      those of the healthcare sector. A good place to start applying human factor
      management to a pharmaceutical safety process would be the complex process
      required to produce a good quality Periodic Safety Update Report (PSUR) on time
      and to an acceptable format. This can be achieved by a process aimed at building
      on an ongoing learning cycle through planning, observing if execution matches
      expectations and learning from mistakes and through the interdependent teamwork
      of PSUR contributors providing mutual support. Such a framework of teamwork and
      communication principles can be applied to the entire process for the preparation
      and submission of PSURs.

PMID- 20812768
TI  - Cardiovascular effects of methylphenidate, amphetamines and atomoxetine in the
      treatment of attention-deficit hyperactivity disorder.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a very common condition in
      children and often extends into the adult years. Drugs such as methylphenidate,
      amphetamines and atomoxetine are frequently prescribed as part of management. The
      use of these drugs has been increasing and significant clinical benefit is
      achieved but safety has been questioned. In this review, the cardiovascular
      safety of these drugs is examined with regard to effects on blood pressure (BP),
      heart rate (HR), ECG parameters and the risk of sudden death. Methylphenidate
      appears to cause minor increases in BP and HR. There are no strong data to
      suggest that methylphenidate increases the corrected QT interval (QTc).
      Amphetamines appear to cause minor increases in HR and BP over the long term.
      There is growing evidence to suggest that amphetamines do not cause statistically
      or clinically significant increases in QTc. Sudden death remains an extremely
      rare event and there is no clear evidence to attribute this to methylphenidate.
      Some data even suggest that the risk of sudden death in treated children may be
      less common than in the background population. Limited data suggest that
      atomoxetine may increase BP and HR in the short term; in the long term it appears
      to increase BP. The effects of atomoxetine on QTc remain uncertain. Use of this
      drug does not appear to be associated with sudden death. Because the current
      evidence is based on research that has not been specifically designed to
      investigate the cardiovascular effects of these drugs it is difficult to draw
      firm conclusions, and further work is required specifically to address these
      questions.

PMID- 20812769
TI  - Proton pump inhibitors and fracture risk: true effect or residual confounding?
AB  - Fracture is a major contributor to human morbidity and mortality, especially in
      the elderly. It has been discussed in the literature that conditions associated
      with decreased stomach acidity may lead to a decrease in intestinal calcium
      absorption and, consequently, to an increased fracture risk. In recent years,
      several observational studies reported a slightly increased fracture risk in
      association with the use of proton pump inhibitors (PPIs) and/or histamine H(2)
      receptor antagonists. It was the objective of this review to critically assess
      the available evidence linking PPI use to an increased fracture risk. A MEDLINE
      and EMBASE search from 1960 to June 2010 was performed to identify the relevant
      articles using predefined search terms. Because (i) there is no proven mechanism,
      (ii) the reported magnitude of the risk elevation associated with the use of PPIs
      was only weak, and (iii) the likelihood of residual confounding despite
      adjustment for known co-morbidities and drug use cannot be ruled out, we conclude
      that the currently available literature does not support the notion that the use
      of PPIs is causally related to a materially increased fracture risk in humans.

PMID- 20812770
TI  - Nature, occurrence and consequences of medication-related adverse events during
      hospitalization: a retrospective chart review in the Netherlands.
AB  - BACKGROUND: Medication-related adverse events (MRAEs) form a large proportion of
      all adverse events in hospitalized patients and are associated with considerable
      preventable harm. Detailed information on harm related to drugs administered
      during hospitalization is scarce. Knowledge of the nature and preventability of
      MRAEs is needed to prioritize and improve medication-related patient safety.
      OBJECTIVE: To provide information on the nature, consequences and preventability
      of MRAEs occurring during hospitalization in the Netherlands. STUDY DESIGN:
      Analysis of MRAEs identified in a retrospective chart review of patients
      hospitalized during 2004. METHODS: The records of 7889 patients admitted to 21
      hospitals in 2004 were reviewed by trained nurses and physicians using a three
      stage process. For each hospital, patient records of 200 discharged and 200
      deceased patients were randomly selected and reviewed. For each patient record,
      characteristics of the patient and the admission were collected. After
      identification of an MRAE the physician reviewers determined the type, severity,
      preventability, drug category and excess length of stay associated with the MRAE.
      Data on additional interventions or procedures related to MRAEs were obtained by
      linking our data to the national hospital registration database. The excess
      length of stay and the additional medical procedures were multiplied by unit
      costs to estimate the total excess direct medical costs associated with the MRAE.
      RESULTS: In total, 148 MRAEs occurred in 140 hospital admissions. The incidence
      of MRAEs was 0.9% (95% CI 0.7, 1.2) and the incidence of preventable MRAEs was
      0.2% (95% CI 0.1, 0.4) per hospital admission. The majority of non-preventable
      MRAEs were adverse drug reactions caused by cancer chemotherapy. Preventable
      MRAEs were most often found in relation to anticoagulant treatment administered
      in combination with NSAIDs. Both non-preventable and preventable MRAEs resulted
      in considerable excess length of hospital stay and costs. On average, MRAEs
      resulted in an excess length of stay of 6.2 days (95% CI 3.6, 8.8) and average
      additional costs of &U20AC;2507 (95% CI 1520, 3773). CONCLUSIONS: This study was
      the first to provide detailed information on MRAEs during hospital admissions in
      the Netherlands, which were associated with both considerable patient harm and
      additional medical costs. To increase patient safety, interventions need to be
      developed that reduce the burden of MRAEs. These interventions should target the
      areas with the highest risk of MRAEs, notably antibacterials, cancer treatment,
      anticoagulant treatment and drug therapy in elderly patients.

PMID- 20812771
TI  - Mapping the safety profile of biologicals: a disproportionality analysis using
      the WHO adverse drug reaction database, VigiBase.
AB  - BACKGROUND: Biologicals have specific characteristics, as compared with the small
      molecule drugs, and carry specific risks. Safety problems, for example infliximab
      and the risk for tuberculosis, have been identified via spontaneous reports of
      suspected adverse drug reactions (ADRs). However, in general there is limited
      data on the nature of spontaneously reported suspected ADRs for biologicals.
      OBJECTIVE: To map the safety profile of biologicals as compared with all other
      drugs. In addition, mechanistic classes of biologicals will be compared. METHODS:
      Data was obtained from the ADR database (VigiBase) maintained by the WHO
      Collaborating Centre for International Drug Monitoring. A disproportionality
      analysis was performed in which case reports for biologicals and all other drugs
      (the reference group), reported between January 1995 and December 2008, were
      selected. Vaccines were not included in the analysis. Suspected ADRs were
      classified according to Medical Dictionary for Regulatory Activities (MedDRA)
      version 12.0 at the System Organ Class (SOC) level. Biologicals were classified
      into mechanistic classes: antibodies, cytokines, enzymes, growth factors,
      hormones (reference group), interferons, receptors and others/various. The safety
      profile of the biologicals versus all other drugs in the database and of the
      various mechanistic classes of biologicals was compared using the proportional
      reporting ratio (PRR). RESULTS: 191,004 case reports containing 546,474 suspected
      ADRs were reported for 62 different biologicals, and 2,556,209 case reports
      containing 8,761,522 suspected ADRs were reported for all other drugs (the
      reference group). It was found that two-thirds of all suspected ADRs reported for
      biologicals were reported for five active substances: etanercept (20.3%),
      interferon-beta-1a (15.6%), infliximab (11.6%), teriparatide (10.7%) and
      adalimumab (9.0%). Comparison of the safety profile of biologicals and the
      reference group showed that suspected ADRs for biologicals were more frequently
      reported in the SOCs 'Infections and infestations' (PRR 4.5), 'Surgical and
      medical procedures' (PRR 2.4) and 'Neoplasms benign, malignant and unspecified'
      (PRR 2.1), and less frequently reported in the SOCs 'Psychiatric disorders' (PRR
      0.4), 'Vascular disorders' (PRR 0.4) and 'Pregnancy, puerperium and perinatal
      conditions' (PRR 0.4). Regarding the differences in safety profile between
      various mechanistic classes of biologicals, compared with hormones (reference
      group), 'Infections and infestations' were more frequently reported for receptors
      and antibodies. 'Neoplasms benign, malignant and unspecified' were more
      frequently reported for antibodies, cytokines, interferons and receptors, and
      less frequently for enzymes as compared with the reference group. CONCLUSIONS: In
      VigiBase, five biologicals comprise two-thirds of the suspected ADRs reported for
      biologicals, which might distort the relation found between a specific biological
      and a specific adverse event in case of quantitative signal detection. Therefore
      the choice of reference group to be used in case of quantitative signal detection
      should be considered very carefully. This study confirmed that biologicals have a
      different safety profile compared with all other drugs in the database and,
      within the group of biologicals, differences exist between mechanistic classes.
      Infections are, for example, frequently reported for receptors and antibodies,
      which often have an immune compromising effect. Such predictable safety issues
      should be specifically studied by preregistration clinical trials and/or targeted
      pharmacovigilance. In addition, since not all adverse reactions can be predicted
      or detected during development, spontaneous reporting remains an important tool
      for the early detection of signals.

PMID- 20812772
TI  - Drug-drug interactions in cardiac and cardiothoracic intensive care units: an
      analysis of patients in an academic medical centre in the US.
AB  - BACKGROUND: Mortality and morbidity are increased in patients experiencing drug
      drug interactions. Unfortunately, there is a paucity of literature describing
      clinically significant drug-drug interactions occurring in the intensive care
      unit (ICU). Knowing the clinically significant drug-drug interactions allows the
      opportunity for prevention through knowledge and computer-assisted programmes.
      OBJECTIVE: To identify significant potential drug-drug interactions occurring in
      the cardiovascular ICU (CCU) and the cardiothoracic ICU (CTICU). STUDY DESIGN:
      Prospective, observational study conducted over a total of 8 weeks in February
      and March 2009. SETTING: CCU and CTICU in a major academic medical centre
      (Presbyterian Hospital, University of Pittsburgh Medical Centre). PATIENTS: All
      adult patients (>or=18 years of age) admitted during 1 month in each ICU.
      INTERVENTION: Micromedex and Lexi-Interact interaction databases were used to
      screen each patient's medication profile daily for the presence of potentially
      interacting drug pairs that would be considered a potential drug-drug
      interaction. A severity assessment using these databases was completed after a
      potential drug-drug interaction was identified. PRIMARY OUTCOME MEASURE: The
      frequency of significant drug-drug interactions, including those that were
      considered major or contraindicated, according to two commercially available
      interaction databases. RESULTS: Evaluations of 400 patient medication profiles
      were conducted, resulting in 225 profiles possessing one or more potential drug
      drug interactions. A total of 1150 potential interactions were identified,
      resulting in 287.5 potential interactions per 100 patient-days. Of the 1150
      potential drug-drug interactions, 458 were unique interacting drug pairs; 5-9% of
      the potential interactions were considered major or contraindicated. Many of the
      significant and frequent potential interactions involved blood coagulation
      modifiers, potential interactions that could result in QTc prolongation, and
      cytochrome P450 inhibition. Micromedex and Lexi-Interact agreed on the severity
      ratings in 20.5% of the potential interactions. CONCLUSIONS: Significant
      potential drug-drug interactions occur in the CCU and CTICU, highlighting the
      need for active surveillance to potentially prevent patient harm. Clinicians
      should also consider using two references for identifying interactions, due to
      the lack of congruence between sources.

PMID- 20812773
TI  - Pharmacovigilance activities in Nepal.

PMID- 20812775
TI  - 2010 Chalmers Oration--what's needed to close the gap?
AB  - The 2010 Chalmers Oration was delivered by Dr Tom Calma on 15 August 2010 at
      Flinders University in Adelaide, South Australia. Dr Calma's presentation
      concerned the groundbreaking roles that he and the Close the Gap Campaign have
      played in making a difference to the health of Indigenous Australians, especially
      those who live in rural and remote Australia.

PMID- 20812776
TI  - Traumatic brain injury exacerbates neurodegenerative pathology: improvement with
      an apolipoprotein E-based therapeutic.
AB  - Cognitive impairment is common following traumatic brain injury (TBI), and
      neuroinflammatory mechanisms may predispose to the development of
      neurodegenerative disease. Apolipoprotein E (apoE) polymorphisms modify
      neuroinflammatory responses, and influence both outcome from acute brain injury
      and the risk of developing neurodegenerative disease. We demonstrate that TBI
      accelerates neurodegenerative pathology in double-transgenic animals expressing
      the common human apoE alleles and mutated amyloid precursor protein, and that
      pathology is exacerbated in the presence of the apoE4 allele. The administration
      of an apoE-mimetic peptide markedly reduced the development of neurodegenerative
      pathology in mice homozygous for apoE3 as well as apoE3/E4 heterozygotes. These
      results demonstrate that TBI accelerates the cardinal neuropathological features
      of neurodegenerative disease, and establishes the potential for apoE mimetic
      therapies in reducing pathology associated with neurodegeneration.

PMID- 20812777
TI  - Post-traumatic hydrocephalus after decompressive craniectomy: an underestimated
      risk factor.
AB  - The incidence of post-traumatic hydrocephalus (PTH) has been reported to be 0.7
      51.4%, and we have frequently observed the development of PTH in patients
      undergoing decompressive craniectomy (DC). For this reason we performed a
      retrospective review of a consecutive series of patients undergoing DC after
      traumatic brain injury (TBI). From January 2006 to December 2009, 41 patients
      underwent DC after closed head injury. Study outcomes focused specifically on the
      development of hydrocephalus after DC. Variables described by other authors to be
      associated with PTH were studied, including advanced age, the timing of
      cranioplasty, higher score on the Fisher grading system, low post-resuscitation
      Glasgow Coma Scale (GCS) score, and cerebrospinal fluid (CSF) infection. We also
      analyzed the influence of the area of craniotomy and the distance of craniotomy
      from the midline. Logistic regression was used with hydrocephalus as the primary
      outcome measure. Of the nine patients who developed hydrocephalus, eight patients
      (89%) had undergone craniotomy with the superior limit <25 mm from the midline.
      This association was statistically significant (p = 0.01 - Fisher's exact test).
      Logistic regression analysis showed that the only factor independently associated
      with the development of hydrocephalus was the distance from the midline. Patients
      with craniotomy whose superior limit was <25 mm from the midline had a markedly
      increased risk of developing hydrocephalus (OR = 17). Craniectomy with a superior
      limit too close to the midline can predispose patients undergoing DC to the
      development of hydrocephalus. We therefore suggest performing wide DCs with the
      superior limit >25 mm from the midline.

PMID- 20812778
TI  - In vitro evaluation of acellular dermal matrix as a three-dimensional scaffold
      for gingival fibroblasts seeding.
AB  - BACKGROUND: Tissue engineering principles could improve the incorporation of
      acellular dermal matrix (ADM). The aim of this study is to verify if ADM is a
      suitable three-dimensional matrix for gingival fibroblasts and cancerous cells
      ingrowth, and also if cultured medium conditioned in ADM affect cellular
      behavior. METHODS: Canine gingival fibroblasts (CGF), human gingival fibroblasts
      (HGF), and murine melanoma cell line (B16F10) were seeded on ADM for up to 14
      days. The following parameters were assessed: morphology and distribution of CGF,
      HGF, and B16F10; CGF and HGF viability; and the effect of ADM conditioned medium
      (CM) on CGF viability. RESULTS: Epifluorescence revealed that CGF were unevenly
      distributed on the ADM surface, showing no increase in cell number over the
      periods of study; HGF formed a monolayer on the ADM surface in a higher number at
      14 days (P <0.05); B16F10 exhibited an increase in cell number within 7 days (P
      <0.05), and were mainly arranged in cell aggregates on the ADM, forming a
      continuous layer at 14 days. A higher percentage of cells on the ADM surface (P
      <0.05) compared to inside was observed for all cell types. 3-[4,5-dimethylthiazol
      2-yl]-2,5-diphenyl tetrazolium bromide (MTT) values indicated higher cell
      viability in samples cultured with HGF compared to CGF (P = 0.024). A
      significantly lower cell viability for CGF grown in CM compared to cells grown in
      non-CM was observed at 48 and 72 hours (P <0.05). CONCLUSIONS: ADM is not
      suitable as a three-dimensional matrix for gingival fibroblasts ingrowth.
      Gingival fibroblasts and highly proliferative cells as B16F10 can only be
      superficially located on ADM, and CGF are negatively affected by culture medium
      conditioned in ADM, reducing its viability.

PMID- 20812779
TI  - Intracellular substrate cleavage: a novel dimension in the biochemistry, biology
      and pathology of matrix metalloproteinases.
AB  - Matrix metalloproteinases (MMPs), originally discovered to function in the
      breakdown of extracellular matrix proteins, have gained the status of regulatory
      proteases in signaling events by liganding and processing hormones, cytokines,
      chemokines, adhesion molecules and other membrane receptors. However, MMPs also
      cleave intracellular substrates and have been demonstrated within cells in
      nuclear, mitochondrial, various vesicular and cytoplasmic compartments, including
      the cytoskeletal intracellular matrix. Unbiased high-throughput degradomics
      approaches have demonstrated that many intracellular proteins are cleaved by
      MMPs, including apoptotic regulators, signal transducers, molecular chaperones,
      cytoskeletal proteins, systemic autoantigens, enzymes in carbohydrate metabolism
      and protein biosynthesis, transcriptional and translational regulators, and
      proteins in charge of protein clearance such as lysosomal and ubiquitination
      enzymes. Besides proteolysis inside cells, intracellular proteins may also be
      modulated by MMPs in the extracellular milieu. Indeed, many intracellular
      proteins exit cells by non-classical secretion mechanisms or by various
      conditions of cell death by apoptosis, necrosis and NETosis, and become
      accessible to extracellular proteases. Intracellular substrate proteolysis by
      MMPs is involved in innate immune defense and apoptosis, and affects oncogenesis
      and pathology of cardiac, neurological, protein conformational and autoimmune
      diseases, including ischemia-reperfusion injury, cardiomyopathy, Parkinson's
      disease, cataract, multiple sclerosis and systemic lupus erythematosus. Since the
      same MMP may affect physiology and pathology in different and even opposite ways,
      depending on its extracellular or subcellular localization, an additional layer
      of complexity is added to therapeutic MMP inhibition. Hence, further elucidation
      of intracellular MMP localizations and intracellular substrate proteolysis is a
      new challenge in MMP research.

PMID- 20812780
TI  - The role of cysteine oxidation in DJ-1 function and dysfunction.
AB  - DJ-1 is a member of the large and functionally diverse DJ-1/PfpI superfamily and
      has homologs in nearly all organisms. Because of its connection to parkinsonism
      and cancer, human DJ-1 has been intensely studied for over a decade. The current
      view is that DJ-1 is a multifunctional oxidative stress response protein that
      defends cells against reactive oxygen species and mitochondrial damage, although
      the details of its biochemical function remain unclear. A conserved cysteine
      residue in DJ-1 (Cys106) is both functionally essential and subject to oxidation
      to the cysteine-sulfinate and cysteine-sulfonate. Consequently, the oxidative
      modification of Cys106 has been proposed to allow DJ-1 to act as a sensor of
      cellular redox homeostasis and to participate in cytoprotective signaling
      pathways in the cell. This review explores the current evidence for the role of
      cysteine oxidation in DJ-1 function, with emphasis on emerging models for how
      oxidative modification may regulate DJ-1's protective function and also
      contribute to dysfunction and disease.

PMID- 20812781
TI  - Thiol/Disulfide redox switches in the regulation of heme binding to proteins.
AB  - This review focuses on thiol/disulfide redox switches that regulate heme binding
      to proteins and modulate their activities. The importance of redox switches in
      metabolic regulation and the general mechanism by which redox switches modulate
      activity are discussed. Methods are described to characterize heme-binding sites
      and to assess their physiological relevance. For thiol/disulfide interconversion
      to regulate activity of a system, the redox process must be reversible at the
      ambient redox potentials found within the cell; thus, methods (and their
      limitations) are discussed that can address the physiological relevance of a
      redox switch. We review recent results that define a mechanism for how
      thiol/disulfide redox switches that control heme binding can regulate the
      activities of an enzyme, heme oxygenase-2, and an ion channel, the BK potassium
      channel. The redox switches on these proteins are composed of different types of
      Cys-containing motifs that have opposite effects on heme affinity, yet have
      complementary effects on hypoxia sensing. Finally, a model is proposed to
      describe how the redox switches on heme oxygenase-2 and the BK channel form an
      interconnected system that is poised to sense oxygen levels in the bloodstream
      and to elicit the hypoxic response when oxygen levels drop below a threshold
      value.

PMID- 20812782
TI  - Interrogation of nucleotide excision repair capacity: impact on platinum-based
      cancer therapy.
AB  - DNA repair is essential for routine monitoring and repair of damage imparted to
      our genetic material by exposure to endogenous and exogenous carcinogens,
      including reactive oxygen species, UV light, and chemicals such as those found in
      cigarette smoke. Without DNA repair pathways, the continual assault on our DNA
      would be highly mutagenic and the risk of cancer increased. Paradoxically, the
      same pathways that help prevent cancer development are detrimental to the
      efficacy of DNA-damaging cancer therapeutics such as cisplatin. Recent studies
      demonstrate the inverse relationship between DNA repair capacity and efficacy of
      platinum-based chemotherapeutics: increased DNA repair capacity leads to
      resistance, while decreased capacity leads to increased sensitivities.
      Cisplatin's cytotoxic effects are mediated by formation of intrastrand DNA
      crosslinks, which are predominantly repaired via the nucleotide excision repair
      (NER) pathway. In an effort to personalize the treatment of cancers based on DNA
      repair capacity, we developed an ELISA-based assay to measure NER activity
      accurately and reproducibly as a prognostic for platinum-based treatments. Here
      we present an overview of DNA repair and its link to cancer and therapeutics. We
      also present data demonstrating the ability to detect the proteins of the pre
      incision complex within the NER pathway from cell and tissue extracts.

PMID- 20812783
TI  - Improving pediatric asthma control among minority children participating in
      medicaid: providing practice redesign support to deliver a chronic care model.
AB  - BACKGROUND: Asthma, a leading chronic disease of children, currently affects
      about 6.2 million (8.5%) children in the United States. Despite advances in
      asthma research and availability of increasingly effective therapy, many children
      do not receive appropriate medications to control the disease, have over-reliance
      on reliever medication, and lack systematic follow-up care. The situation is even
      worse for poor inner-city and minority children who have significantly worse
      asthma rates, severity, and outcomes. National Asthma Education and Prevention
      Program Guidelines recommend a multimodal, chronic care approach. OBJECTIVE: The
      authors assessed the effectiveness of practice redesign and computerized provider
      feedback in improving both practitioner adherence to National Asthma Education
      and Prevention Program Guidelines (NAEPP), and patient outcomes in 295 poor
      minority children across four Federally Qualified Health Centers (FQHC). METHODS:
      In a nonrandomized, two-group (intervention versus comparison), two-phase trial,
      all sites were provided redesign support to provide quarterly well-asthma visits
      using structured visit forms, community health workers for outreach and follow
      up, a Web-based disease registry for tracking and scheduling, and a provider
      education package. Intervention sites were given an additional Web-based,
      computerized patient-specific provider feedback system that produced a guideline
      driven medication assessment prompt. RESULTS: Logistic regression results showed
      that providers at intervention sites were more than twice as likely on average to
      prescribe guideline-appropriate medications after exposure to our feedback system
      during the Phase I enrollment period than providers at comparison sites (exp(B) =
      2.351, confidence interval [CI] = 1.315-4.204). In Phase II (the post-enrollment
      visit period), hierarchical linear models (HLMs) and latent growth curves were
      used to show that asthma control improved significantly by .19 (SE = .05) on
      average for each of the remaining four visits (about 11% of a standard
      deviation), and improved even more for patients at intervention sites. These
      results show that implementation of practice redesign support guided by a
      pediatric chronic care model can improve provider adherence to treatment
      guidelines as well as patients' asthma control. CONCLUSIONS: The addition of
      patient-specific feedback for providers results in quicker adoption of guideline
      recommendations and potentially greater improvements in asthma control compared
      to the basic practice redesign support alone.

PMID- 20812784
TI  - Trans-plasma membrane electron transport in mammals: functional significance in
      health and disease.
AB  - Trans-plasma membrane electron transport (t-PMET) has been established since the
      1960s, but it has only been subject to more intensive research in the last
      decade. The discovery and characterization at the molecular level of its novel
      components has increased our understanding of how t-PMET regulates distinct
      cellular functions. This review will give an update on t-PMET, with particular
      emphasis on how its malfunction relates to some diseases, such as cancer,
      abnormal cell death, cardiovascular diseases, aging, obesity, neurodegenerative
      diseases, pulmonary fibrosis, asthma, and genetically linked pathologies.
      Understanding these relationships may provide novel therapeutic approaches for
      pathologies associated with unbalanced redox state.

PMID- 20812786
TI  - Cortical networks representing object categories and high-level attributes of
      familiar real-world action sounds.
AB  - In contrast to visual object processing, relatively little is known about how the
      human brain processes everyday real-world sounds, transforming highly complex
      acoustic signals into representations of meaningful events or auditory objects.
      We recently reported a fourfold cortical dissociation for representing action
      (nonvocalization) sounds correctly categorized as having been produced by human,
      animal, mechanical, or environmental sources. However, it was unclear how
      consistent those network representations were across individuals, given potential
      differences between each participant's degree of familiarity with the studied
      sounds. Moreover, it was unclear what, if any, auditory perceptual attributes
      might further distinguish the four conceptual sound-source categories,
      potentially revealing what might drive the cortical network organization for
      representing acoustic knowledge. Here, we used functional magnetic resonance
      imaging to test participants before and after extensive listening experience with
      action sounds, and tested for cortices that might be sensitive to each of three
      different high-level perceptual attributes relating to how a listener associates
      or interacts with the sound source. These included the sound's perceived
      concreteness, effectuality (ability to be affected by the listener), and spatial
      scale. Despite some variation of networks for environmental sounds, our results
      verified the stability of a fourfold dissociation of category-specific networks
      for real-world action sounds both before and after familiarity training.
      Additionally, we identified cortical regions parametrically modulated by each of
      the three high-level perceptual sound attributes. We propose that these
      attributes contribute to the network-level encoding of category-specific acoustic
      knowledge representations.

PMID- 20812787
TI  - Selenium in human health and disease.
AB  - This review covers current knowledge of selenium in the environment, dietary
      intakes, metabolism and status, functions in the body, thyroid hormone
      metabolism, antioxidant defense systems and oxidative metabolism, and the immune
      system. Selenium toxicity and links between deficiency and Keshan disease and
      Kashin-Beck disease are described. The relationships between selenium
      intake/status and various health outcomes, in particular gastrointestinal and
      prostate cancer, cardiovascular disease, diabetes, and male fertility, are
      reviewed, and recent developments in genetics of selenoproteins are outlined. The
      rationale behind current dietary reference intakes of selenium is explained, and
      examples of differences between countries and/or expert bodies are given.
      Throughout the review, gaps in knowledge and research requirements are
      identified. More research is needed to improve our understanding of selenium
      metabolism and requirements for optimal health. Functions of the majority of the
      selenoproteins await characterization, the mechanism of absorption has yet to be
      identified, measures of status need to be developed, and effects of genotype on
      metabolism require further investigation. The relationships between selenium
      intake/status and health, or risk of disease, are complex but require elucidation
      to inform clinical practice, to refine dietary recommendations, and to develop
      effective public health policies.

PMID- 20812788
TI  - Iron-sulfur clusters: biogenesis, molecular mechanisms, and their functional
      significance.
AB  - Iron-sulfur clusters [Fe-S] are small, ubiquitous inorganic cofactors
      representing one of the earliest catalysts during biomolecule evolution and are
      involved in fundamental biological reactions, including regulation of enzyme
      activity, mitochondrial respiration, ribosome biogenesis, cofactor biogenesis,
      gene expression regulation, and nucleotide metabolism. Although simple in
      structure, [Fe-S] biogenesis requires complex protein machineries and pathways
      for assembly. [Fe-S] are assembled from cysteine-derived sulfur and iron onto
      scaffold proteins followed by transfer to recipient apoproteins. Several
      predominant iron-sulfur biogenesis systems have been identified, including
      nitrogen fixation (NIF), sulfur utilization factor (SUF), iron-sulfur cluster
      (ISC), and cytosolic iron-sulfur protein assembly (CIA), and many protein
      components have been identified and characterized. In eukaryotes ISC is mainly
      localized to mitochondria, cytosolic iron-sulfur protein assembly to the cytosol,
      whereas plant sulfur utilization factor is localized mainly to plastids. Because
      of this spatial separation, evidence suggests cross-talk mediated by organelle
      export machineries and dual targeting mechanisms. Although research efforts in
      understanding iron-sulfur biogenesis has been centered on bacteria, yeast, and
      plants, recent efforts have implicated inappropriate [Fe-S] biogenesis to
      underlie many human diseases. In this review we detail our current understanding
      of [Fe-S] biogenesis across species boundaries highlighting evolutionary
      conservation and divergence and assembling our knowledge into a cellular context.

PMID- 20812789
TI  - Noninvasive monitoring of cerebrovascular reactivity with near infrared
      spectroscopy in head-injured patients.
AB  - Monitoring of cerebrovascular pressure reactivity (PRx) has diagnostic and
      prognostic value in head-injured patients, but requires invasive monitoring of
      intracranial pressure (ICP). Near infrared spectroscopy (NIRS) is a noninvasive
      method that is suitable for continuous detection of cerebral blood volume
      changes. We compared a NIRS-based index of cerebrovascular reactivity, called
      total hemoglobin reactivity (THx), against standard measurements of PRx in a
      prospective observational study. Forty patients with closed-head injury were
      monitored daily with arterial blood pressure (ABP), ICP, and a NIRS-based total
      hemoglobin index. PRx and THx were calculated as the moving correlation
      coefficients using 5-min time windows between 10-sec averaged values of ICP and
      ABP, and total hemoglobin index and ABP, respectively. A total of 120 recordings
      were performed between the median first (IQR 0.75-2) and fourth (IQR 2-6) day
      after head injury, giving a total duration of 1760 hours. PRx and THx
      demonstrated a significant association across averaged individual recordings (r =
      0.49, p < 0.0001), and across patients (r = 0.56, p = 0.0002). Assessment of
      optimal cerebral perfusion pressure (CPP) and ABP using THx was possible in about
      50% of recordings, and showed a significant agreement with the optimal CPP and
      ABP assessed with PRx. THx may be of diagnostic value to optimize therapy
      oriented toward restoration and continuity of cerebrovascular reactivity,
      especially in patients for whom direct ICP monitoring is not feasible.

PMID- 20812790
TI  - Epoetin theta: efficacy and safety of IV administration in anaemic haemodialysis
      patients in the maintenance phase in comparison to epoetin beta.
AB  - OBJECTIVE: To compare the efficacy and safety of epoetin theta and epoetin beta
      in anaemic patients with chronic kidney disease, undergoing haemodialysis and
      previously on stable maintenance therapy with epoetin beta. METHODS: In this
      multicentre, randomised, controlled, double-blind study 270 haemodialysis
      patients were treated intravenously (i.v.) for 24 weeks with either epoetin theta
      (n = 180) or epoetin beta (n = 90). The primary efficacy endpoint was the change
      in haemoglobin (Hb) from baseline to end of treatment (efficacy evaluation
      period, EEP, weeks 15-26). Hb levels, weekly doses of epoetin theta or epoetin
      beta required to maintain Hb levels, dose changes, safety, tolerability and
      immunogenicity were evaluated. CLINICAL TRIAL REGISTRATION: EudraCT No. 2005
      000143-28. RESULTS: Mean Hb values were similar in both treatment groups at
      baseline and during the 24-weeks treatment period. The estimated treatment
      difference between epoetin theta and epoetin beta from baseline to EEP was -0.01
      g/dL (95% confidence interval: -0.24, 0.21), p = 0.9021, indicating that the
      difference between both groups was not statistically significant. The weekly
      doses of epoetin theta or epoetin beta required to maintain Hb levels were nearly
      the same. The changes from baseline to EEP in patients who switched to treatment
      with epoetin theta (95.5-99.7 IU/kg(BW)) were smaller than in patients staying on
      their epoetin beta therapy (89.0-98.0 IU/kg(BW)). The profile and the frequency
      of adverse drug reactions (ADRs) were similar in both treatment groups (21.7%
      epoetin theta; 22.2% epoetin beta). The most common ADRs were hypertension,
      headache and arteriovenous fistula thrombosis. None of the patients developed
      anti-erythropoietin antibodies. CONCLUSIONS: Epoetin theta (i.v.) has a similar
      efficacy compared to epoetin beta (i.v.) in haemodialysis patients based on Hb
      changes from baseline to end of treatment (non-inferiority). The safety profile
      was similar in both groups. Patients could be switched from maintenance treatment
      with epoetin beta to epoetin theta without relevant dose changes.

PMID- 20812791
TI  - Reasons for discontinuation and continuation of antipsychotics in the treatment
      of schizophrenia from patient and clinician perspectives.
AB  - OBJECTIVE: To identify reasons for discontinuation and continuation of
      antipsychotic medications in the treatment of schizophrenia from the patients'
      and their clinicians' perspectives. RESEARCH DESIGN AND METHODS: Two measures
      were previously developed to assess the Reasons for Antipsychotic
      Discontinuation/Continuation (RAD), one from the patient's perspective and
      another from the clinician's perspective. These measures were administered to
      acutely ill schizophrenia patients enrolled in a 12-week study of antipsychotic
      medications (N = 596) and to their clinicians. The RAD was assessed at baseline
      and at endpoint. Reasons were rated on a 5-point scale from 'primary reason' to
      'not a reason.' The single most important reason was also identified. The 'single
      most important reason' and the 'primary reasons' for discontinuing the drug used
      prior to enrollment, and for discontinuing or continuing the study drug were
      identified. Levels of concordance between patients' and clinicians' reasons were
      assessed. CLINICAL TRIAL REGISTRATION: The data source for this study is a
      clinical trial registered at www.clinicaltrials.gov (NCT00337662). MAIN OUTCOME
      MEASURES: Reasons for Antipsychotic Discontinuation/Continuation (RAD). RESULTS:
      Patients and clinicians identified several reasons for medication discontinuation
      and continuation (2.3 to 6.3 reasons, on average). The top 'single most
      important' reason for discontinuing the drug used prior to enrollment and for
      discontinuing the study drug was 'positive symptoms not sufficiently improved or
      made worse,' followed by 'medication-related adverse events.' The most frequent
      'single most important' reason for medication continuation was 'improved positive
      symptoms,' followed by 'patient's perception of improvement,' and 'functional
      improvement.' A high level of concordance was observed between patients' and
      clinicians' ratings. CONCLUSIONS: Medication efficacy appears to be the core
      driver of medication discontinuation and continuation, especially with regard to
      positive symptoms. There was a high level of concordance between patients' and
      clinicians' perspectives. Limitations include the study requirement that patients
      be at least moderately ill and experiencing acute psychotic exacerbation, a
      potential selection bias in the readiness to respond to measures, and small
      sample sizes for some analyses. Further research is needed to replicate findings
      in patients who are not acutely ill.

PMID- 20812792
TI  - The effect of pregabalin on pain-related sleep interference in diabetic
      peripheral neuropathy or postherpetic neuralgia: a review of nine clinical
      trials.
AB  - OBJECTIVE: Postherpetic neuralgia and painful diabetic peripheral neuropathy are
      common chronic neuropathic pain conditions associated with sleep disturbances.
      Pregabalin is indicated in the treatment of neuropathic pain. The objective of
      this review is to summarize the efficacy and safety of pregabalin in painful
      diabetic peripheral neuropathy and postherpetic neuralgia and the effect of
      pregabalin on sleep interference in these patients. METHODS: MEDLINE and ISI Web
      of Knowledge databases were searched for randomized double-blind, placebo
      controlled clinical trials of pregabalin reporting sleep measures in addition to
      pain endpoints in patients with painful diabetic peripheral neuropathy and
      postherpetic neuralgia published from inception through March 2009. RESULTS: Nine
      trials met the inclusion criteria, providing data for a total of 2399 patients
      with painful diabetic peripheral neuropathy or postherpetic neuralgia treated
      twice or three times per day with pregabalin (75-600 mg/day) or placebo on a
      fixed or flexible schedule. Interpretation of sleep outcomes in two studies may
      be limited by trial inclusion criteria which permitted benzodiazepines for sleep
      problems. Also, none of the studies reported objective sleep measures. Pregabalin
      was well tolerated. Pregabalin (150-600 mg/day) significantly reduced pain and
      improved pain-related sleep interference. CONCLUSIONS: In addition to an
      analgesic benefit, pregabalin may decrease pain-related sleep interference in
      patients with painful diabetic peripheral neuropathy and postherpetic neuralgia.

PMID- 20812785
TI  - Aging and immune function: molecular mechanisms to interventions.
AB  - Abstract The immune system of an organism is an essential component of the
      defense mechanism aimed at combating pathogenic stress. Age-associated immune
      dysfunction, also dubbed "immune senescence," manifests as increased
      susceptibility to infections, increased onset and progression of autoimmune
      diseases, and onset of neoplasia. Over the years, extensive research has
      generated consensus in terms of the phenotypic and functional defects within the
      immune system in various organisms, including humans. Indeed, age-associated
      alterations such as thymic involution, T cell repertoire skewing, decreased
      ability to activate naive T cells and to generate robust memory responses, have
      been shown to have a causative role in immune decline. Further, understanding the
      molecular mechanisms underlying the generation of proteotoxic stress, DNA damage
      response, modulation of ubiquitin proteasome pathway, and regulation of
      transcription factor NFkappaB activation, in immune decline, have paved the way
      to delineating signaling pathways that cross-talk and impact immune senescence.
      Given the role of the immune system in combating infections, its effectiveness
      with age may well be a marker of health and a predictor of longevity. It is
      therefore believed that a better understanding of the mechanisms underlying
      immune senescence will lead to an effective interventional strategy aimed at
      improving the health span of individuals. Antioxid. Redox Signal. 14, 1551-1585.

PMID- 20812793
TI  - Cost effectiveness of deferasirox compared to desferrioxamine in the treatment of
      iron overload in lower-risk, transfusion-dependent myelodysplastic syndrome
      patients.
AB  - OBJECTIVE: The study evaluated the cost effectiveness of deferasirox (Exjade * )
      compared to non-proprietary desferrioxamine (DFO) for the control of
      transfusional iron overload in lower risk myelodysplastic syndromes (MDS)
      patients. A UK National Health Service perspective was adopted. METHODS: Recent
      clinical evidence has demonstrated the efficacy and safety of deferasirox in
      transfusion-dependent MDS patients with elevated serum ferritin levels. An
      economic model was used to extrapolate the clinical benefits of iron chelation
      therapy (ICT) in a cohort of lower risk MDS patients. Costs for drug acquisition,
      drug administration and monitoring, and quality of life (utility) outcomes
      associated with mode of drug administration were derived from a variety of
      sources. The incremental cost per QALY gained for deferasirox was estimated.
      Costs and outcomes were discounted at 3.5% in line with UK standards. RESULTS:
      The base-case cost effectiveness of deferasirox versus DFO was estimated to be
      L20,822 per QALY gained, the key driver being the additional quality of life
      benefits associated with a simpler mode of administration for deferasirox. A mean
      survival benefit for both forms of ICT of 4.5 years was estimated. The results
      were sensitive to drug dose, days of DFO administration, and patient weight.
      CONCLUSIONS: In the UK, a cost per QALY below L20,000-30,000 is considered cost
      effective. Hence, the results from this economic analysis suggest deferasirox is
      cost effective in lower risk, transfusion-dependent, MDS patients. Limitations
      with the analysis include a lack of comparative randomised controlled trial
      evidence, in particular to differentiate survival and clinical outcomes for
      deferasirox and DFO.

PMID- 20812794
TI  - History and science.

PMID- 20812795
TI  - German flooding of the Pontine Marshes in World War II.
AB  - The German army's 1943 flooding of the Pontine Marshes south of Rome, which later
      caused a sharp rise in malaria cases among Italian civilians, has recently been
      described by historian Frank Snowden as a unique instance of biological warfare
      and bioterrorism in the European theater of war and, consequently, as a violation
      of the 1925 Geneva Protocol prohibiting chemical and biological warfare. We argue
      that archival documents fail to support this allegation, on several counts. As a
      matter of historical record, Hitler prohibited German biological weapons (BW)
      development and consistently adhered to the Geneva Protocol. Rather than
      biological warfare against civilians, the Wehrmacht used flooding, land mines,
      and the destruction of vital infrastructure to obstruct the Allied advance. To
      protect its own troops in the area, the German army sought to contain the
      increased mosquito breeding likely to be caused by the flooding. Italians
      returning to the Pontine Marshes after the German retreat in 1944 suffered
      malaria as a result of environmental destruction, which was banned by the 1899
      and 1907 Hague Conventions and by subsequent treaties. In contrast, a state's
      violation of the Geneva Protocol, whether past or present, involves the use of
      germ weapons and, by inference, a state-level capability. Any allegation of such
      a serious violation demands credible evidence that meets high scientific and
      legal standards of proof.

PMID- 20812796
TI  - Biopolitical science.
AB  - This article develops a theoretical framework for biopolitical science as a
      science of political animals. This science moves through three levels of deep
      political history: the universal political history of the species, the cultural
      political history of the group, and the individual political history of animals
      in the group. To illustrate the particular application of biopolitical science,
      this essay shows how this science would help us to understand Abraham Lincoln's
      Emancipation Proclamation of January 1, 1863.

PMID- 20812797
TI  - Genuine fakes.
AB  - This case study of the Australian Museum's Thylacine Cloning Project analyzes a
      frame dispute that emerged during public communication of a scientific project,
      which lasted from 1999 to 2005, and was premised on the idea of resurrecting an
      extinct species. In choosing the Tasmanian tiger--an iconic Australian marsupial
      officially declared extinct in 1986--the promoters of the cloning project ensured
      extensive media coverage. However, the popular and scientific attention generated
      by the idea of bringing back an extinct species challenged the Museum's efforts
      to frame the project in terms of scientific progress. The project repeatedly
      shifted from science to spectacle, as multiple stakeholders used the mass media
      to negotiate the scientific feasibility of trying to reverse extinction through
      the application of advanced biotechnology. The case study findings are relevant
      both to the emerging social issues surrounding the use of paleogenomics in
      wildlife conservation, and to the theoretical development of frame analysis as
      applied to scientific controversies.

PMID- 20812798
TI  - Darwin, artificial selection, and poverty.
AB  - This paper argues that the processes of evolutionary selection are becoming
      increasingly artificial, a trend that goes against the belief in a purely natural
      selection process claimed by Darwin's natural selection theory. Artificial
      selection is mentioned by Darwin, but it was ignored by Social Darwinists, and it
      is all but absent in neo-Darwinian thinking. This omission results in an
      underestimation of probable impacts of artificial selection upon assumed
      evolutionary processes, and has implications for the ideological uses of Darwin's
      language, particularly in relation to poverty and other social inequalities. The
      influence of artificial selection on genotypic and phenotypic adaptations
      arguably represents a substantial shift in the presumed path of evolution, a
      shift laden with both biological and political implications.

PMID- 20812799
TI  - Reconsidering genetic virtue.

PMID- 20812800
TI  - Enhancing genetic virtue?

PMID- 20812801
TI  - The tempting illusion of genetic virtue.

PMID- 20812802
TI  - Can virtue be genetically engineered?

PMID- 20812803
TI  - Genetically engineered people.

PMID- 20812804
TI  - Objecting to the Genetic Virtue Program.

PMID- 20812805
TI  - Moral suasion, installed.

PMID- 20812806
TI  - In defense of the Genetic Virtue Program.

PMID- 20812810
TI  - Psychometric methods.

PMID- 20812811
TI  - Multidimensional scaling.

PMID- 20812812
TI  - Perceived social support and depression among Veterans with multiple sclerosis.
AB  - PURPOSE: To examine the association between perceived social support and self
      reported depression among Veterans of the US Armed Forces ('Veterans') with
      multiple sclerosis (MS), and differences in this relationship between specific
      support subtypes (tangible, positive social interaction, emotional/informational
      and affective). METHOD: Participants were Veterans with MS (N = 451) receiving
      medical services through the Veterans Health Administration who completed mailed
      surveys. Hierarchical regression examined the extent to which global perceived
      social support concurrently predicted depression among a predominantly male
      sample of individuals with MS. Exploratory correlational analyses examined the
      relationship between specific subtypes of perceived social support and
      depression. RESULTS: Greater global perceived social support was associated with
      less depression after controlling for sociodemographic and disease-related
      variables. In follow-up analyses examining specific subtypes of support, greater
      positive social interaction, greater emotional/informational support, and greater
      affective support were related to less depression. There was no relationship
      between perceived tangible support and depression. CONCLUSIONS: Interventions
      aimed at increasing positive social interactions, expressed affection and
      emotional/information support may be particularly helpful for individuals with MS
      and their caregivers.

PMID- 20812813
TI  - Employment experiences among adolescents and young adults with cystic fibrosis.
AB  - PURPOSE: We sought to examine the employment experiences in a population of
      adolescents and young adults with cystic fibrosis (CF). METHODS: We administered
      a cross-sectional survey to 68 individuals with CF, ages 16-25 years, assessing
      current employment experiences and perceptions of the impact of CF on these
      experiences. RESULTS: Forty-six percent of respondents reported working < 20 h
      per week. Sixty-seven percent reported disclosing their diagnosis to their
      employer. Only one respondent reported receiving formal job guidance in CF
      clinic, and only 16% reported that a clinician had discussed job-related issues
      with them. Only 21% reported that they completed CF therapies at work. Older
      respondents (ages 22-25 years) and those with a lower lung function were more
      likely to agree that 'balancing employment and CF care is stressful.'
      CONCLUSIONS: The majority of adolescents and young adults with CF report
      disclosing their diagnosis at work. Most do not feel that working interferes with
      routine CF therapies. Very few have received any formal career guidance. Age and
      lung disease severity are associated with increased concerns about balancing CF
      care and employment.

PMID- 20812814
TI  - Perceived service and support needs during transition from hospital to home
      following acquired brain injury.
AB  - OBJECTIVE: To explore the service and support needs of individuals with acquired
      brain injury (ABI) and their family caregivers during the transition phase from
      hospital to home. METHODS: The study utilised a qualitative research design.
      Participants included 20 individuals with ABI and 18 family caregivers recruited
      from a specialist inpatient brain injury rehabilitation unit. Data collection
      entailed in-depth semi-structured interviews, which were conducted at three time
      points: pre-discharge, and 1- and 3-months post-discharge. Thematic analysis of
      the interview transcripts involved open, axial and selective coding techniques.
      RESULTS: The following primary themes, each with associated secondary themes,
      emerged from the analysis: (1) balancing the service and support equation; (2)
      negotiating the rehabilitation maze; (3) working with or against 'the system'.
      The first theme describes the varying types and level of support received by
      participants during the transition phase, while the second theme highlights the
      difficulties participants experienced in negotiating the rehabilitation process
      between hospital and home. The final theme depicts the challenges experienced by
      participants in accessing and utilising service support. CONCLUSIONS: The
      findings suggest that the scope of existing service models need to be extended to
      bridge the existing gap between inpatient and community services, thereby easing
      the impact of transition.

PMID- 20812815
TI  - Cancer in experimental animals exposed to arsenic and arsenic compounds.
AB  - Inorganic arsenic is a ubiquitous environmental contaminant that has long been
      considered a human carcinogen. Recent studies raise further concern about the
      metalloid as a major, naturally occurring carcinogen in the environment. However,
      during this same period it has proven difficult to provide experimental evidence
      of the carcinogenicity of inorganic arsenic in laboratory animals and, until
      recently, there was considered to be a lack of clear evidence for carcinogenicity
      of any arsenical in animals. More recent work with arsenical methylation
      metabolites and early life exposures to inorganic arsenic has now provided
      evidence of carcinogenicity in rodents. Given that tens of millions of people
      worldwide are exposed to potentially unhealthy levels of environmental arsenic,
      in vivo rodent models of arsenic carcinogenesis are a clear necessity for
      resolving critical issues, such as mechanisms of action, target tissue
      specificity, and sensitive subpopulations, and in developing strategies to reduce
      cancers in exposed human populations. This work reviews the available rodent
      studies considered relevant to carcinogenic assessment of arsenicals, taking
      advantage of the most recent review by the International Agency for Research on
      Cancer (IARC) that has not yet appeared as a full monograph but has been
      summarized (IARC, 2009 , IARC Special Report: Policy, Vol. 10. Lyon: IARC Press,
      453-454). Many valid studies show that arsenic can interact with other
      carcinogens/agents to enhance oncogenesis, and help elucidate mechanisms, and
      these too are summarized in this review. Finally, this body of rodent work is
      discussed in light of its impact on mechanisms and in the context of the
      persistent argument that arsenic is not carcinogenic in animals.

PMID- 20812816
TI  - Physical activity, sedentariness, and body fatness in a sample of 6-year-old
      Pacific children.
AB  - OBJECTIVE: Pacific children living in New Zealand exhibit considerably higher
      rates of overweight and obesity than their non-Pacific peers. The study aim was
      to identify physical activity and sedentary behaviors related to increased body
      size in Pacific children, to inform future intervention development for improved
      activity profiles and body size outcomes in this population. METHODS: Three
      hundred and ninety-three 6-year-old Pacific children and their mothers living in
      Auckland, New Zealand were invited to participate. Activity was assessed over 8
      days using accelerometry and mothers reported on their child's sedentary
      behaviours. Children's height, weight, and body fatness was assessed and body
      mass index (BMI) and body fat z-scores calculated. Maternal height, weight, and
      waist circumference were assessed and BMI calculated. Associations between
      children's body fat z-scores and potential related factors were determined using
      regression analyses. RESULTS: Of the 254 children who registered, 102 (27%
      overweight, 32% obese) were included in analyses. Almost all mothers were
      overweight or obese. On average, children's body fat z-scores were 1.75 standard
      deviations above the reference group (range -0.6, 3.14). After accounting for all
      other factors, watching television every day and having a mother with a high
      waist circumference were associated with increased body fat z-scores.
      CONCLUSIONS: Strategies for obesity reduction in Pacific children and their
      mothers living in New Zealand are urgently required. Multifaceted, family based
      interventions that include the promotion of healthy nutritional practices and
      television free days may be efficacious in improving activity profiles and body
      size outcomes for Pacific children.

PMID- 20812818
TI  - Letter in response to the new SHEA guideline for healthcare workers with
      hepatitis B virus, hepatitis C virus, and/or human immunodeficiency virus.

PMID- 20812820
TI  - Chlorhexidine is not the main active ingredient in skin antiseptics that reduce
      blood culture contamination rates.

PMID- 20812822
TI  - Healthcare workers with methicillin-resistant Staphylococcus aureus colonization
      and the use of contact precautions in daily activities with patients in an
      Italian rehabilitation hospital: the importance of hand hygiene training.

PMID- 20812823
TI  - Central venous catheter flushing and an outbreak of bacteremia among pediatric
      hematology-oncology patients.

PMID- 20812824
TI  - Clinicopathological study of lacrimal sac specimens obtained during DCR.
AB  - PURPOSE: To determine the histopathologic characteristics of lacrimal sac
      specimens in adult patients undergoing external dacryocystorhinostomy (DCR) for
      acquired nasolacrimal duct obstruction. METHODS: A total of 471 lacrimal sac
      biopsies were obtained from 449 patients undergoing external DCR for symptoms or
      signs of acquired nasolacrimal duct obstruction and examined histopathologically.
      RESULTS: A total of 449 subjects including 283 (63%) female and 166 (37%) male
      subjects with mean age of 50.02 years underwent DCR and histopathologic
      examination of specimens. Presenting symptoms were epiphora in 411 patients
      (91%), history of acute dacryocystitis in 17 patients (4%) and obstruction
      revealed during ophthalmic examinations in 21 patients (5%). Histopathologic
      findings included: chronic inflammation in 450 patients (95.5%), fibrosis in 18
      patients (3.8%), lymphoma in two patients (0.4%) and reactive lymphoid
      hyperplasia in one patient (0.2%). Lacrimal sac appearance during surgery was
      grossly abnormal in two cases: one case of lymphoma and one instance of reactive
      lymphoid hyperplasia. CONCLUSIONS: Chronic inflammation and fibrosis are the most
      common histopathologic findings in lacrimal sac specimens obtained during DCR.
      Only two cases of lymphoma (0.4%) were encountered in the series, one of which
      had a suspicious lacrimal sac appearance during surgery while the other case
      (0.2% of all specimens) was unsuspected. The rate of malignant etiology for NLD
      obstruction is low enough to justify lacrimal sac biopsy only in suspicious
      cases.

PMID- 20812825
TI  - Brown tumor of the orbital roof as an initial and isolated manifestation of
      secondary hyperparathyroidism.
AB  - Brown tumors appear in advanced stages of hyperparathyroidism. Only 17 cases have
      been documented in the orbit. We report a case of a young woman with a brown
      tumor in the orbital roof. Secondary hyperparathyroidism due to chronic renal
      disease was detected during the preoperative study. The pathogenesis, diagnosis
      and management of the brown tumor are discussed.

PMID- 20812826
TI  - The role of intravenous methylprednisolone immunosuppression in the management of
      active thyroid eye disease.
AB  - PURPOSE: To analyze the efficacy of intravenous methylprednisolone (IVMP)
      immunosuppression in the management of active thyroid eye disease (TED). METHODS:
      This is a consecutive case series of 36 patients treated with 1 g of IVMP over 3
      days, between January 2000 and January 2008. The indications for this treatment
      were moderate to severe active TED with or without optic nerve compression.
      RESULTS: There were 32 hyperthyroid, 2 hypothyroid, and 2 euthyroid patients in
      this series. Nine patients presented with optic nerve compromise, 3 had severe
      active TED and 24 had moderately active TED. Twenty-seven patients received one
      course of IVMP and nine patients received two courses. All patients had tapering
      oral prednisolone over 1 month following the IVMP. The mean improvement in
      proptosis was 1.31 mm (range = 0-3 mm). Optic nerve function improved in seven of
      nine patients (77.8%). Extra ocular muscle movement improved in 18 patients
      (50%). Overall benefit from IVMP was seen at 1/12 in 27 patients (75%) and at
      3/12 in 30 patients (83%). After IVMP one patient underwent radiotherapy and
      three patients had nonsteroidal immunosuppression. CONCLUSIONS:  IVMP
      immunosuppression is effective in 83% of patients. The effect lasts from 3 months
      to 8 years, with a mean of 15 months in 30.5%. It remains a useful modality of
      treatment especially when the optic nerve or cornea is threatened because of
      moderate to severe active TED. We encountered no severe side effects of pulsed
      IVMP and 3 g over 3 days is a safe dose.

PMID- 20812827
TI  - Clinical features and surgical management of orbitotemporal neurofibromatosis: a
      retrospective interventional case series.
AB  - PURPOSE: To evaluate the clinical features and surgical preferences of patients
      with neurofibromatosis. METHODS: Histologically confirmed neurofibromatosis cases
      that underwent surgery during a 15-year period were retrospectively evaluated.
      The patients' demographics, severity of periorbital involvement, aim of surgery,
      surgery types, postoperative outcome, and complications were recorded. RESULTS:
      Nineteen patients with a mean age of 24.7 +/- 21.2 years were included in the
      study. Nine were younger and 10 were older than 16 years. Seventeen patients had
      unilateral and two had bilateral involvement. Patients were followed for a mean
      of 5.8 +/- 5.7 years. A total of 35 surgeries were performed. In 22 times the
      surgery was performed to improve vision, and in others to get a cosmetically
      acceptable appearance. Although there was an improvement in visual acuity, the
      difference was not significant (P = 0.085). Debulking of the tumor was performed
      in 100%, ptosis surgery in 90%, and lateral canthal fixation in 50% of surgeries.
      All patients showed improvement: at the last examination, six eyes had no ptosis,
      in 13 eyes ptosis not covering the pupil in primary gaze was observed on the
      involved side, and in only one eye the pupil was half covered. CONCLUSION: In
      neurofibromatosis the treatment should be customized to each patient. As
      confirmed in our study, an open visual axis is the main goal in surgery, followed
      by cosmetic appearance. The authors believe that, with possibly multiple
      surgeries an acceptable result can be achieved.

PMID- 20812828
TI  - Watery eye following patent external DCR: an MR dacryocystography study.
AB  - PURPOSE: To examine patients with persistent watery epiphora following patent
      external dacryocystorhinostomy (DCR) with magnetic resonance imaging
      dacryocystography (MR-DCG). METHODS: Patients with unobstructed nasolacrimal
      irrigation following external DCR were included. Five patients with watery
      epiphora constituted the study group (SG). Five patients without epiphora
      constituted the control group (CG). All patients underwent MR-DCG following the
      instillation of artificial tears in the conjunctival fornix. The osteotomy site
      was identified in T1-weighted coronal images. Lacrimal flow was assessed with
      modified T2-weighted (True Fast Imaging Steady State Pulse, "TrueFISP") coronal
      images before and 10 min after repeated blinking. Signal intensities at three
      regions of interest (ROIs), corresponding to the eyeball (ROI-1), conjunctival
      sac (ROI-2), and anastomotic site (ROI-3) were measured. RESULTS: Differences in
      the diameter of both osseous and soft tissue ostia between SG and CG were
      statistically not significant. A post-blink increase in signal intensity at ROI-3
      was noted in both groups, whereas differences in signal intensity for ROI-1 and
      ROI-2 were statistically not significant. The post-blink signal intensity
      increase in ROI-3 was significantly more pronounced in the CG, compared with the
      SG. CONCLUSIONS: The fact that signal intensity increase at ROI-3 was less
      pronounced in the SG, compared with CG, implies a compromised "lacrimal pump"
      mechanism in the former group. The methodology presented may be used for the
      evaluation of post-DCR epiphora.

PMID- 20812829
TI  - Effective orbital volume and eyeball position: an MRI study.
AB  - PURPOSE: Previous studies have examined factors affecting the position of the
      eyeball to the orbit. This study examined the role of effective orbital volume
      (EOV), defined as the difference between orbital and eyeball volume, as a
      determinant of eyeball position, using MRI scans. METHODS: Forty-six patients
      were recruited from the Department of Ophthalmology of the University Hospital of
      Heraklion, Crete Greece. Patients with a history of orbital disease were
      excluded. Distances between eyeball poles and orbital landmarks were measured in
      T1 weighted transverse, sagittal and coronal orbital images. The protrusion of
      the eyeball in the sagittal and transverse planes was recorded. The volume of the
      eyeball and bony orbit, the EOV, the volume of the extraocular muscles as well as
      clinical information (age, gender, Hertel exophthalmometry) were also recorded.
      RESULTS: EOV was significantly associated with orbital volume but not with
      eyeball volume. EOV was also significantly associated with transverse and
      sagittal globe protrusions. Females displayed significantly lower orbital and
      eyeball volumes as well as EOV than males but higher transverse globe protrusion
      than males. CONCLUSIONS: Variations in EOV are associated with orbital volume
      rather than with eyeball volume. EOV is associated with globe protrusion and may
      be taken into account in the planning of various procedures, including orbital
      decompression, treatment of enophthalmos or the size of orbital implants
      following enucleation.

PMID- 20812830
TI  - Complications of intracanalicular plugs: a case series.
AB  - PURPOSE: Intracanalicular plugs are commonly used in the management of dry eyes.
      The authors report 3 cases of complications associated with intracanalicular
      plugs. METHODS: Clinical findings and the management of these patients are
      presented. RESULTS: The first patient (case 1) is a 47-year-old female with
      severe dry eyes. Six months after insertion of intracanalicular Form fit hydrogel
      plugs (OASIS Medical) she developed canaliculitis with Klebsiella oxytoca. The
      second patient (case 2), a 33-year-old female, who developed left canalicular
      abscess 5 months following the insertion of bilateral, intracanalicular Form fit
      hydrogel plugs (OASIS Medical). The third patient (case 3) a 33-year-old female
      had granulation tissue formation within the left lower canaliculus, 5 years after
      insertion of intracanalicular plug. The symptoms in the three patients resolved
      after they underwent canaliculotomy with removal of the plugs. CONCLUSION:
      Complications of intracanalicular plugs can sometimes outweigh their benefits.
      These plugs can lodge in the lacrimal outflow system and cause pyogenic granuloma
      formation and canaliculitis. To our knowledge, until now there have been no
      reports of complications associated with Form Fit hydrogel plugs (OASIS Medical)
      and its infective complication with Klebsiella oxytoca.

PMID- 20812831
TI  - Surgical management of heavy eye phenomenon.
AB  - Heavy eye phenomenon can be cosmetically unaccepted due to significant
      pseudoproptosis and hypotropia. We highlight the salient features of this
      condition, and report successful cosmetic outcome following a staged procedure
      comprising orbital decompression and horizontal recti surgery.

PMID- 20812832
TI  - Small versus coronal incision orbital decompression in Graves' orbitopathy.
AB  - Ideally the planning of decompression surgery should be adequate to the severity
      of the orbitopathy, its possible "lipogenic" or "myopathic" variants, the
      patient's specific orbital osteology and possible previous surgeries. Due to
      surgeon's experience and local traditions, however, a standardized rather than a
      tailored approach is often offered to the patient. An inferior fornix incision
      can be used for infero medial bony decompression and/or for removing fat from the
      medial and lateral inferior orbital quadrants. Through the same route a lateral
      osteotomy can also be performed although an upper skin crease incision offers a
      wider access to the lateral orbital wall. As an alternative the swinging eyelid
      technique, offering an adequate access to the bony orbit and to the orbital fat
      compartments is a versatile technique that can virtually be used as a standard
      approach for the greatest majority of patients needing decompression surgery.
      Orbital decompression by coronal incision is an invasive technique and for this
      not to be used as a standard approach to orbital decompression. Nevertheless, it
      is not to be abandoned as it can be an additional tool in surgeons' hands when
      dealing with patients who can better benefit out of a particular, tailored rather
      than a standardised approach. Many are the circumstances in which this may
      happen. Major complications associated with the coronal approach have been mainly
      described in small series, where only a few patients per year were operated. In
      this respect it is therefore unavoidable to emphasize that each technique has its
      own learning curve and it may be difficult to differentiate the effects of each
      technique from the experience of the surgeon.

PMID- 20812833
TI  - The use of autologous dermis grafts for the reconstruction of the anophthalmic
      socket.
AB  - PURPOSE: The main objectives of enucleation, evisceration or secondary orbital
      implants are to replace orbital volume and obtain good motility and adaptation of
      the implant and the external prosthesis. We describe our experience using
      autologous dermis graft sutured to Tenon and conjunctiva following evisceration,
      enucleation and any reconstruction requiring either a primary or secondary
      orbital implant, even those with large tissue loss. MATERIALS AND METHODS: A
      retrospective case series of patients who received an autologous dermis graft to
      assist in closure of a Tenon's capsule and conjunctiva at the time of placement
      of secondary orbital implants or evisceration or enucleation with fornices
      retraction or tension in tissues. We also describe how and from where to take the
      dermis graft. RESULTS: 72 patients were included and all received orbital porous
      polyethylene implants: 28 patients had secondary orbital implants, 36 patients
      had evisceration and 8 patients had enucleation. Implant size was 20 mm in most
      cases, but went to 22 mm. Follow-up ranged from 3 to 36 months. No intraoperative
      complications were observed in donor or receptor area. 8 cases had incipient
      ischemia of the dermis graft, but were treated and resolved with autologous
      serum. CONCLUSIONS: Implant exposure is due to bad surgical technique, an
      inadequate implant size or excessive tension on the suture. Dermis autologous
      graft allows moving the orbital implant anteriorly because it replaces surface to
      suture Tenon and conjunctiva without tension, so a good adaptation of a thinner
      external prosthesis is possible, resulting in better motility.

PMID- 20812835
TI  - Tie hard 2- an in-vitro comparison of first throw tension holding in twisted v
      straight-first throws; using Polyglycolic acid (Dexon S), Polyglactin 910 (Coated
      Vicryl).
AB  - OBJECTIVE: To compare the first throw tension holding properties of twisted
      versus straight first throws in two commonly used Oculoplastic braided absorbable
      sutures. DESIGN: An in-vitro experimental model. METHODS: Variable loads were
      applied to the first double throw of a surgical knot - either in straight-line
      configuration or twisting the knot using both 6/0 Polyglycolic acid (Dexon S) and
      6/0 Polyglactin 910 (Coated Vicryl). Each suture was tested to the point of knot
      slipping and the critical tension recorded. Two variations of the experiment were
      undertaken: Experiment 1 - two metal loops were brought together by the test
      suture, experiment 2 - two strips of tissue (Permacol - cross-linked porcine
      dermal collagen) were brought together by the test suture. RESULTS: Experiment 1
      straight: Polyglycolic acid 12.2g (11-13.5), Polyglactin-910 2.5 g (2.5- no
      range). Experiment 1 twisted: Polyglycolic acid 13.33 g (10-15), Polyglactin 910
      3 g (2-5). Experiment 2 straight: Polyglycolic acid 33g (30-35), Polyglactin 910
      25g (25 - no range). Experiment 2 twisted: Polyglycolic acid 35 (30-40),
      Polyglactin 910 25g (20-30). CONCLUSIONS: Twisting the suture adds only a modest
      increase in first throw knot security. Polyglycolic acid (Dexon S) braided
      absorbable suture has significantly better first throw knot security when
      compared with Polyglactin-910 (coated Vicryl). This is an important property when
      suturing tissues under tension as it minimises slippage before the locking throw
      is tied.

PMID- 20812834
TI  - Optic nerve biopsy via a medial transconjunctival orbitotomy approach in the
      diagnosis of optic nerve and sheath tumors.
AB  - PURPOSE: To evaluate the role of optic nerve biopsy in the diagnosis and
      management of optic nerve and sheath tumors. METHODS: Seven patients with
      progressive optic nerve and sheath tumors for whom treatment was deemed necessary
      were included in this study. Optic nerve biopsy via a medial transconjunctival
      orbitotomy approach was performed in all patients RESULTS: There were no
      complications related to the surgical procedure. Histopathological examination
      revealed that five patients had juvenile pilocytic astrocytoma (JPA) and two
      patients had optic nerve sheath meningioma (ONSM). All patients received external
      beam radiotherapy (EBRT). CONCLUSIONS: Many other benign and malignant optic
      nerve and sheath tumors have imaging features similar to those seen in JPA and
      ONSM. Therefore, it is important to establish histopathologic diagnosis before
      embarking on treatment. Furthermore, tissue diagnosis is required prior to EBRT
      in many institutions because of concerns about medicolegal liability. Optic nerve
      biopsy via a transconjunctival orbitotomy procedure in seven patients yielded
      histopathologic confirmation of the existing pathology and was not associated
      with any complications in this series.

PMID- 20812836
TI  - Nasal endoscopic assessment of failure after external dacryocystorhinostomy.
AB  - PURPOSE: To study intranasal causes of failure of external dacryocystorhinostomy
      (DCR). DESIGN: A retrospective study of clinical data from transnasal endoscopic
      findings after failure of external DCR. METHODS: Assessment of 65 patients with
      failure after external dacryocystorhinostomy; subjectively by patient's symptoms
      and saccharine test and objectively by patency on syringing, functional
      endoscopic dye test and endonasal endoscopic assessment. RESULTS: Endoscopic
      findings revealed: 20 cases intranasal adhesions, 8 cases septal deviation and
      concha bullosa, 8 cases abnormal size fistula, 6 cases rhinosinusitis, 6 cases
      contact granuloma, 3 cases of pouch, 4 cases closed ostium, 10 cases no definite
      cause could be found (functional failure). Negative dye clearance test and non
      detection of fluorescein on irrigatiom in 55 patients. Delayed dye clearance but
      detection of fluorescein on irrigation in 10 patients (functional failure).
      CONCLUSIONS: Nasal endoscopy is very important in diagnosing causes of failure of
      external DCR. Nasal endoscopy is essential before and after external DCR. DCR
      should be done by a team work of rhinologist and ophthalmologist. Study of
      mucociliary clearance of lacrimal pathway will help to improve our surgeries and
      whether to do small or large fenestra technique.

PMID- 20812837
TI  - The orbital fibroblast: a key player and target for therapy in graves'
      ophthalmopathy.
AB  - Orbital fibroblasts play a key role in the pathogenesis of Graves' ophthalmopathy
      (GO). We discuss some major aspects by which orbital fibroblasts contribute to GO
      and the important role of PDGF-BB herein. Finally, we propose the orbital
      fibroblast, and especially the PDGF system acting on orbital fibroblasts, as an
      important therapeutic target in GO.

PMID- 20812838
TI  - A simplified marking technique for eyebrow reconstruction using composite grafts.
AB  - Eyebrows can be damaged in facial burns, trauma, skin cancer, herpes zoster and
      other conditions. Some of these patients will demand eyebrow reconstruction
      surgery. This can be done using free composite grafts from the scalp or flaps
      from the temporal area. Both techniques require time-consuming planning, marking
      and shaping of the graft or flap in order to achieve a good cosmetic result. In
      an attempt to make free graft reconstructions faster and easier, we modified the
      technique. We describe an easy way of obtaining a template that simplifies the
      procedure and enhances symmetry.

PMID- 20812839
TI  - Our experience with dermofat graft in reconstruction of anophthalmic socket.
AB  - PURPOSE: To present our experience with dermofat graft in reconstruction of
      anophthalmic socket. MATERIAL AND METHODS: In period from September 2005 until
      June 2009, eight patients have undergone orbital surgery of transplantation of
      dermofat graft. In six patients the dermofat graft was used as the secondary
      orbital implant after extrusion of hydroxyapatite orbital implant with major
      defect of bulbar conjunctiva. The other indication for the dermofat graft was
      correction of deep superior sulcus of the upper lid in anophthalmic socket in two
      patients. The graft was harvested from the left side of the belly. The size of
      the graft purposely exceeded the size of the defect to account for the expected
      tissue resorption. RESULTS: We experienced no major complication. Approximately
      20-40% of dermofat graft reduction was noticed in 3-months period
      postoperatively. It took 6-8 weeks for the graft to fully epithelize from the
      conjunctival edge. Silicone conformer was introduced for that period of time.
      Subsequently, in two out of six patients with dermofat graft as the secondary
      implant, fornix had to be reconstructed later on with oral mucosa graft.
      CONCLUSION: Dermofat graft is a valuable material in orbital reconstruction
      especially in anophthalmic socket.

PMID- 20812840
TI  - Prostatic adenocarcinoma presenting with metastatic frontal bone involvement and
      orbital invasion.
AB  - We present a rare case of prostatic adenocarcinoma presenting with metastatic
      frontal bone involvement with subsequent spread to the orbit. Although prostatic
      adenocarcinoma has a strong tendency to metastasize to bone, particularly axial
      skeletal bone, frontal bone involvement is rare and subsequent orbital
      involvement is even more so.

PMID- 20812841
TI  - Fibrous dysplasia.
AB  - An atypical presentation of fibrous dysplasia with a very large cystic component
      is described. The MR pattern was not diagnostic.

PMID- 20812842
TI  - Solitary orbital paget disease: a case report.
AB  - PURPOSE: To describe the clinical findings in a patient who had developed
      painless supraorbital prominence. METHODS: Clinical and histopathological
      findings of the case are reviewed and presented. RESULTS: The patient had an
      isolated histologically confirmed Paget disease of the orbit. Local excision of
      the lesion was performed. CONCLUSION: Paget disease can present not only as a
      diffuse process but also as a painless, solitary lesion of the orbit.

PMID- 20812843
TI  - Chronic lymphedema of the eyelid: case series.
AB  - PURPOSE: To evaluate the clinical features, management and outcomes of treatment
      of chronic lymphedema of the eyelid in a tertiary referral setting. DESIGN:
      Retrospective case series. PARTICIPANTS: 15 patients referred to the authors with
      unilateral or bilateral eyelid swelling of greater than 3 months duration. MAIN
      OUTCOME MEASURES: Clinical features, patient management, response to treatment.
      RESULTS: Chronic eyelid lymphedema was associated with acne rosacea in 9
      patients, radiotherapy in 1 patient, trauma in 1 patient and post-vitrectomy
      silicone oil leak in 1 patient. In the remaining 4 patients no associated
      condition or factor was identified. Surgical debulking was performed in 9 cases
      with improvement in all cases and no complications. CONCLUSION: Chronic eyelid
      lymphedema is a rare condition most commonly associated with rosacea. In our
      experience, surgical resection of involved subcutaneous tissue was helpful.

PMID- 20812844
TI  - Preclinical evaluation of a recombinant adeno-associated virus vector expressing
      human alpha-1 antitrypsin made using a recombinant herpes simplex virus
      production method.
AB  - Recombinant adeno-associated virus (rAAV) vectors offer promise for gene therapy
      of alpha-1 antitrypsin (AAT) deficiency. A toxicology study in mice evaluated
      intramuscular injection of an rAAV vector expressing human AAT (rAAV-CB-hAAT)
      produced using a herpes simplex virus (HSV) complementation system or a plasmid
      transfection (TFX) method at doses of 3 * 10(11) vg (1.2 * 10(13) vg/kg) for both
      vectors and 2 * 10(12) vg (8 * 10(13) vg/kg) for the HSV-produced vector. The HSV
      produced vector had favorable in vitro characteristics in terms of purity,
      efficiency of transduction, and hAAT expression. There were no significant
      differences in clinical findings or hematology and clinical chemistry values
      between test article and control groups and no gross pathology findings.
      Histopathological examination demonstrated minimal to mild changes in skeletal
      muscle at the injection site, consisting of focal chronic interstitial
      inflammation and muscle degeneration, regeneration, and vacuolization, in vector
      injected animals. At the 3 * 10(11) vg dose, serum hAAT levels were higher with
      the HSV-produced vector than with the TFX-produced vector. With the higher dose
      of HSV-produced vector, the increase in serum hAAT levels was dose-proportional
      in females and greater than dose-proportional in males. Vector copy numbers in
      blood were highest 24 hr after dosing and declined thereafter, with no detectable
      copies present 90 days after dosing. Antibodies to hAAT were detected in almost
      all vector-treated animals, and antibodies to HSV were detected in most animals
      that received the highest vector dose. These results support continued
      development of rAAV-CB-hAAT for treatment of AAT deficiency.

PMID- 20812845
TI  - Maternal human leukocyte antigen A*2301 is associated with increased mother-to
      child HIV-1 transmission.
AB  - We examined associations between maternal human leukocyte antigen (HLA) and
      vertical human immunodeficiency virus type 1 (HIV-1) transmission in a perinatal
      cohort of 277 HIV-infected women in Nairobi. HLA class I genes were amplified by
      using sequence-specific oligonucleotide probes, and analyses were performed using
      logistic regression. Maternal HLA-A*2301 was associated with increased
      transmission risk before and after adjusting for maternal viral load (unadjusted:
      odds ratio [OR], 3.21; 95% confidence interval [CI], 1.42-7.27; P = .005; Pcorr =
      0.04; adjusted: OR, 3.07; 95% CI, 1.26-7.51; P =.01; Pcorr is not significant).
      That maternal HLA-A*2301 was associated with transmission independent of plasma
      HIV-1 RNA levels suggests that HLA may alter infectivity through mechanisms other
      than influencing HIV-1 load.

PMID- 20812846
TI  - A sustained hospital outbreak of vancomycin-resistant Enterococcus faecium
      bacteremia due to emergence of vanB E. faecium sequence type 203.
AB  - BACKGROUND: A significant increase in the rate of vancomycin-resistant
      Enterococcus faecium (VREfm) bacteremia at our health service, despite improved
      infection control, prompted us to investigate the cause. METHODS: E. faecium
      bacteremia (including VREfm) over a 12-year period (1998-2009) was investigated
      using multilocus sequence typing, antibiotic and antiseptic susceptibility
      profiles, optical mapping, and whole genome sequencing of historical and recent
      isolates. RESULTS: For 10 years, the rate of bacteremia due to vanB VREfm
      remained stable and sequence type (ST) 17 was predominant. In 2005, ST203
      vancomycin-susceptible E. faecium first appeared at our institution, and from
      March 2007, coinciding with the appearance of a vanB VREfm ST203, the rate of VRE
      bacteremia has increased exponentially. Although we found no difference in
      antiseptic susceptibility or presence of genes encoding putative virulence
      determinants (esp(Efm), hyl(Efm), and fms genes), comparative genomics revealed
      almost 500 kb of unique sequence when an ST17 and an ST203 VREfm isolate were
      compared, suggesting that other genomic factors are responsible for the apparent
      success of E. faecium. CONCLUSIONS: The application of multilocus sequence typing
      has uncovered the emergence of an epidemic clone of E. faecium ST203 that appears
      to have acquired the vanB locus and has caused a sustained outbreak of VRE
      bacteremia.

PMID- 20812847
TI  - Influence of a single nucleotide polymorphism at the main ribavirin transporter
      gene on the rapid virological response to pegylated interferon-ribavirin therapy
      in patients with chronic hepatitis C virus infection.
AB  - The equilibrative nucleoside transporter 1 (ENT1) is the main protein involved in
      ribavirin cellular uptake. Polymorphisms at the ENT1 gene may influence ribavirin
      activity as part of hepatitis C virus (HCV) therapy. A retrospective study was
      conducted in 109 human immunodeficiency virus (HIV)-infected patients who were
      infected with HCV genotypes 1 or 4 who had received pegylated interferon (pegIFN)
      ribavirin. Single nucleotide polymorphisms (SNPs) at the ENT1 gene were examined
      using TaqMan 5'-nuclease assays. In the study population, allelic frequencies at
      rs760370 were as follows: A3 (43 [39%] of 109 patients), AG (50 [46%] of 109
      patients), and GG (16 [15%] of 109 patients). Achievement of rapid virological
      response was more frequent in GG carriers than in AA/AG carriers (50% vs 17%,
      respectively; P = .007). In multivariate analysis, the GG genotype (odds ratio
      [OR], 15.9; 95% confidence interval [CI], 2.8-92.2; P < .002), a baseline serum
      HCV-RNA level <600,000 IU/mL (OR, 45.7; 95% CI, 8.7-240.5; P <.001) and a serum
      ribavirin trough concentration >2.5 MUg/mL (OR, 4.8; 95% CI, 1.3-17.1; P < .016)
      were associated with rapid virological response. When 2 or more of these factors
      were present, positive and negative predictive values of rapid virological
      response were 65% and 91%, respectively. In summary, a SNP rs760370A->G at the
      ENT1 gene influences the chance of rapid virological response to pegIFN-ribavirin
      therapy in HIV-infected patients with chronic HCV infection due to HCV genotypes
      1 or 4, most likely modulating intracellular ribavirin exposure within
      hepatocytes.

PMID- 20812848
TI  - Biological determinants of immune reconstitution in HIV-infected patients
      receiving antiretroviral therapy: the role of interleukin 7 and interleukin 7
      receptor alpha and microbial translocation.
AB  - BACKGROUND: Multiple host factors may influence CD4(+) T cell reconstitution in
      human immunodeficiency virus (HIV)-infected patients after suppressive
      antiretroviral therapy (ART). We hypothesized that residual immune activation and
      polymorphisms in the interleukin 7 (IL-7) receptor alpha (IL-7Ralpha) gene were
      important for immune recovery. METHODS: We examined HIV-infected patients
      receiving suppressive ART (n = 96) for their IL-7Ralpha haplotypes and measured
      levels of lipopolysaccharide (LPS), soluble CD14, and IL-7 in plasma samples
      collected before and after ART initiation. Levels of soluble IL-7Ralpha were
      measured in HIV-infected patients with IL-7Ralpha haplotype 2 (n = 11) and those
      without IL-7Ralpha haplotype 2 (n = 22). Multivariate analysis was used to
      identify variables associated with faster recovery to CD4(+) T cell counts of
      >500 and >200 cells/MUL. RESULTS: Both LPS and soluble CD14 levels were
      significantly decreased with ART (P < .001, respectively) but remained elevated
      compared with uninfected controls. In a multivariate analysis, faster recovery to
      a CD4(+) T cell count of >500 cells/MUL was significantly associated with higher
      baseline CD4(+) T cell count, younger age, lower pre-ART LPS level, higher pre
      ART soluble CD14 level, lower pre-ART IL-7 level, and IL-7Ralpha haplotype 2
      (hazard ratio, 1.50; 95% confidence interval, 1.03-2.19; P = .034). HIV-infected
      patients with haplotype 2 had significantly lower soluble IL-7Ralpha levels
      compared with those of patients without haplotype 2 (P < .001). CONCLUSION: Both
      the extent of immune depletion prior to ART and IL-7Ralpha haplotype 2 are
      important determinants of time to CD4(+) T cell recovery to counts of >500
      cells/MUL.

PMID- 20812849
TI  - Development of genital warts after incident detection of human papillomavirus
      infection in young men.
AB  - Determining the rate at which men develop genital warts after infection with
      alpha genus human papillomavirus (HPV) types will provide important information
      for the design of prevention strategies. We conducted a cohort study of 18-21
      year-old men who underwent triannual genital examinations. The 24-month
      cumulative genital wart incidence was 57.9% (95% confidence interval [CI], 38.1%
      79.1%) among 46 men with incident detection of HPV-6 or HPV-11 infection, 2.0%
      (95% CI, 0.5%-7.9%) among 161 men with incident detection of infection with other
      HPV types, and 0.7% (95% CI, 0.2%-2.8%) among 331 men who tested negative for
      HPV. Our results suggest that genital warts are common after HPV-6 or HPV-11
      infection in young men.

PMID- 20812850
TI  - Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in HIV
      1-infected men.
AB  - BACKGROUND: Human immunodeficiency virus type 1 (HIV-1)-infected men are at
      increased risk for anal cancer. Human papillomavirus (HPV) vaccination may
      prevent anal cancer caused by vaccine types. METHODS: AIDS Malignancy Consortium
      Protocol 052 is a single-arm, open-label, multicenter clinical trial to assess
      the safety and immunogenicity of the quadrivalent HPV (types 6, 11, 16, and 18)
      vaccine in HIV-1-infected men. Men with high-grade anal intraepithelial neoplasia
      or anal cancer by history or by screening cytology or histology were excluded.
      Men received 0.5 mL intramuscularly at entry, week 8, and week 24. The primary
      end points were seroconversion to vaccine types at week 28, in men who were
      seronegative and without anal infection with the relevant HPV type at entry, and
      grade 3 or higher adverse events related to vaccination. RESULTS: There were no
      grade 3 or greater adverse events attributable to vaccination among the 109 men
      who received at least 1 vaccine dose. Seroconversion was observed for all 4
      types: type 6 (59 [98%] of 60), type 11 (67 [99%] of 68), type 16 (62 [100%] of
      62), and type 18 (74 [95%] of 78). No adverse effects on CD4 counts and plasma
      HIV-1 RNA levels were observed. CONCLUSIONS: The quadrivalent HPV vaccine appears
      safe and highly immunogenic in HIV-1-infected men. Efficacy studies in HIV-1
      infected men are warranted. Clinical trials registration. NCT 00513526.

PMID- 20812852
TI  - Physical activity and mental health in a student population.
AB  - BACKGROUND: A growing body of literature indicates that physical activity can
      have beneficial effects on mental health. However, previous research has mainly
      focussed on clinical populations, and little is known about the psychological
      effects of physical activity in those without clinically defined disorders. AIMS:
      The present study investigates the association between physical activity and
      mental health in an undergraduate university population based in the United
      Kingdom. METHOD: One hundred students completed questionnaires measuring their
      levels of anxiety and depression using the Hospital Anxiety and Depression Scale
      (HADS) and their physical activity regime using the Physical Activity
      Questionnaire (PAQ). RESULTS: Significant differences were observed between the
      low, medium and high exercise groups on the mental health scales, indicating
      better mental health for those who engage in more exercise. CONCLUSIONS:
      Engagement in physical activity can be an important contributory factor in the
      mental health of undergraduate students.

PMID- 20812851
TI  - Interferon gamma responses to mycobacterial antigens protect against subsequent
      HIV-associated tuberculosis.
AB  - BACKGROUND: The cellular immune responses that protect against tuberculosis have
      not been identified. METHODS: We assessed baseline interferon gamma (IFN-gamma)
      and lymphocyte proliferation assay (LPA) responses to antigen 85 (Ag85), early
      secretory antigenic target 6 (ESAT-6), and Mycobacterium tuberculosis whole cell
      lysate (WCL) in human immunodeficiency virus (HIV)-infected and bacille Calmette
      Guerin (BCG)-immunized adults with CD4 cell counts of >or= 200 cells/MUL who
      received placebo in the DarDar tuberculosis vaccine trial in Tanzania. Subjects
      were followed prospectively to diagnose definite or probable tuberculosis.
      RESULTS: Tuberculosis was diagnosed in 92 of 979 subjects during a mean follow-up
      of 3.2 years. The relative risk of tuberculosis among subjects with positive IFN
      gamma responses to Ag85 was 0.51 (95% confidence interval [CI], 0.26-0.99; P =
      .049), to ESAT-6 was 0.44 (95% CI, 0.23-0.85; P = .004), and to WCL was 0.67 (95%
      CI, 0.49-0.88; P = .002). The relative risk of tuberculosis was not significantly
      associated with baseline LPA responses. In a multivariate Cox regression model,
      subjects with IFN-gamma responses to ESAT-6 and WCL had a lower hazard of
      developing tuberculosis, with a hazard ratio for ESAT-6 of 0.35 (95% CI, 0.16
      0.77; P = .009) and a hazard ratio for WCL of 0.30 (95% CI, 0.16-0.56; P < .001).
      CONCLUSIONS: Baseline IFN-gamma responses to ESAT-6 and WCL were associated with
      protection from subsequent tuberculosis among HIV-infected subjects with
      childhood BCG immunization in a region of high tuberculosis prevalence. Trial
      registration. ClinicalTrials.gov identifier: NCT00052195.

PMID- 20812853
TI  - Assessment of the factor structure and reliability of the Portuguese version of
      the General Health Questionnaire-28 among adults.
AB  - BACKGROUND: The General Health Questionnaire (GHQ, Goldberg & Hillier, 1979 ,
      Psychological Medicine, 9, 139-145) is a self-administered questionnaire used to
      measure non-psychotic psychiatric disorders. There is a study using a Portuguese
      version of this questionnaire (n = 60) including a group of inpatients with
      infectious diseases (Ribeiro & Antunes, 2003 , Revista Portuguesa de
      Psicossomatica, 5(1), 37-45), but there are no larger studies in non-clinical
      Portuguese population. AIMS: The primary aim of the study was to confirm the
      psychometric properties of the Portuguese version of the GHQ-28 among 171
      Portuguese adults in non-clinical settings. METHODS: The Portuguese version of
      the GHQ-28 was administered to 171 adult subjects of Portuguese general
      population. RESULTS: The Portuguese version of the GHQ-28 has an internally
      consistent measure Cronbach's alpha 0.922 for the GHQ-28 total scale. For the
      subscale somatic symptoms Cronbach's alpha was 0.825; for the subscale Anxiety/
      Insomnia, Cronbach's alpha was 0.873; for the subscale Social dysfunction
      Cronbach's alpha was 0.873 and for the subscale Severe Depression was 0.838. Four
      factors were extracted using factor analysis: somatic symptoms (items 1-7);
      anxiety/insomnia (items 8-14); psychosocial dysfunction (items 15-21); and severe
      depression (items 22-28). CONCLUSIONS: The findings suggest that the GHQ-28 is a
      suitable screening instrument for adult Portuguese population in non-clinical
      settings.

PMID- 20812854
TI  - The Meriden Family Programme: lessons learned over 10 years.
AB  - BACKGROUND: Psychoeducational family approaches are effective in improving the
      quality of life for both those with mental health problems and their families,
      but implementation of these approaches within health services has been limited.
      The Meriden Family Programme has provided training and support for over 3,900
      therapists and 242 trainers in Behavioural Family Therapy (BFT) to encourage
      widespread delivery of effective services for families with a member who has
      psychosis or other serious mental health problems. AIMS: This article synthesises
      healthcare professionals' and carers' views on the implementation of family work
      and ways of increasing family involvement in services. METHODS: During the
      Meriden Programme's 10th anniversary year, three Masterclass groups (n = 27) were
      conducted with healthcare professionals and carers involved with the programme
      over the past 10 years. RESULTS: A collaborative approach between management,
      commissioners, BFT trainers, therapists, carers and service users encourages and
      ensures the delivery of family work. The most effective types of support, methods
      of training and organisational factors in supporting family work implementation
      are illustrated. CONCLUSIONS: Best practices in implementing family work are
      identified to support and better inform those responsible for providing family
      work within their services.

PMID- 20812855
TI  - The role of head-in-space stability on stepping reactions in young and elderly
      adults.
AB  - This study compared head kinematic responses and step latency following an
      anteriorly directed postural perturbation between two groups (Young, mean age
      27.39; Elderly, mean age 71.9). We further attempted to demonstrate, for the
      first time, a positive linear relationship between sagittal plane head angular
      velocities and stepping responses in both groups. It was hypothesized that the
      Elderly would demonstrate higher head angular velocities and greater step
      latencies than the Young. We also hypothesized that a positive linear
      relationship would show that, following a perturbation, trials where head angular
      velocity was low yielded quicker step responses. Each participant experienced
      three perturbations under five different visual conditions designed to alter
      visual input and head/trunk coordination. Repeated-measures ANOVA was used, with
      alpha set at 0.05. For each test condition, the Elderly consistently demonstrated
      longer step latencies while exhibiting higher head angular velocities. For each
      group, a positive linear relationship was shown between the two dependent
      variables (Young: r=0.86; Elderly, r=0.84). During a postural perturbation, as
      head angular velocity increased, stepping responses were delayed.

PMID- 20812856
TI  - Knee extension isometric torque production differences based on verbal motivation
      given to introverted and extroverted female children.
AB  - To date, little research has been conducted to test the efficacy of different
      forms of motivation based on a female child's personality type. The purpose of
      this study was to evaluate the ability of female children to perform a maximal
      knee extension isometric torque test with varying forms of motivation, based on
      the child's personality type (introvert vs. extrovert). The subjects were asked
      to perform a maximal isometric knee extension test under three different
      conditions: 1) with no verbal motivation, 2) with verbal motivation from the
      evaluator only, and 3) with verbal motivation from a group of their peers and the
      evaluator combined. A 2*3 mixed ANOVA was significant for an interaction (F
      2,62=17.530; p<0.0005). Post hoc testing for the introverted group showed that
      scores without verbal motivation were significantly higher than with verbal
      motivation from the evaluator or the evaluator plus the peers. The extroverted
      group revealed that scores with verbal motivation from the evaluator or the
      evaluator plus the peers were significantly higher than without verbal
      motivation. Results suggest that verbal motivation has a varying effect on
      isometric knee extension torque production in female children with different
      personality types. Extroverted girls perform better with motivation, whereas
      introverted girls perform better without motivation from others.

PMID- 20812857
TI  - Recurrent conjunctivitis and scleritis secondary to coexistent conjunctival
      pemiphigus vulgaris and cryptic herpes simplex infection: a case report.
AB  - PURPOSE: To report recurrent conjunctivitis and scleritis secondary to coexistent
      conjunctival pemiphigus vulgaris and cryptic herpes simplex infection. DESIGN:
      Case report. METHODS: Retrospective review. RESULTS: A 54-year-old woman
      presented with recurrent left eye irritation and redness. Four years earlier, she
      was diagnosed (biopsy) with cutaneous pemphigus vulgaris requiring
      immunomodulatory therapies. She was receiving oral acyclovir for recurrent
      genital herpes and intravenous immunoglobulin for pemphigus. Examination revealed
      unilateral necrotizing scleritis and conjunctivitis. Immunohistochemical staining
      of biopsies demonstrated conjunctival pemphigus and herpes in conjunctiva and
      sclera. Valacyclovir therapy brought resolution. CONCLUSION: Cryptic ocular
      herpes may confound matters in someone with an autoimmune disease thought to be
      the sole source of ocular inflammation. Immunohistochemical analysis can resolve
      the mystery.

PMID- 20812858
TI  - Autophagy shapes inflammation.
AB  - Autophagy is a basic cell biological process ongoing under physiologic
      circumstances in almost all cell types of the human organism and upregulated by
      various stress conditions including those leading to inflammation. Since
      autophagy affects the effector cells of innate and adaptive immunity mediating
      the inflammatory response, its activity in these cells influences the
      antimicrobial response, the development of an effective cognate immune defense,
      and the course of the normal sterile inflammatory reactions. The level of
      autophagic activity may determine whether tissue cells die by apoptosis,
      necrosis, or through autophagy, and, as a consequence, whether the clearance of
      these dying cells is a silent process or results in an inflammatory response.
      Loss or decreased autophagy may lead to necrotic death that can initiate an
      inflammatory reaction in phagocytes through their surface and cytosolic
      receptors. Engulfment of certain cells dying through autophagy can activate the
      inflammasome. The intertwining regulatory connections between inflammation and
      immunity extend to pathologic conditions including chronic inflammatory diseases,
      autoimmunity and cancer.

PMID- 20812859
TI  - Protease inhibitors as models for the study of oxidative folding.
AB  - The correct balance between proteases and their natural protein inhibitors is of
      great importance in living systems. Protease inhibitors usually comprise small
      folds that are crosslinked by a high number of disulfide bonds, making them
      perfect models for the study of oxidative folding. To date, the oxidative folding
      of numerous protease inhibitors has been analyzed, revealing a great diversity of
      folding pathways that differ mainly in the heterogeneity and native disulfide
      bond content of their intermediates. The two extremes of this diversity are
      represented by bovine pancreatic trypsin inhibitor and hirudin, which fold,
      respectively, via few native intermediates and heterogeneous scrambled isomers.
      Other proteins, such as leech carboxypeptidase inhibitor, share characteristics
      of both models displaying mixed folding pathways. The study of the oxidative
      folding of two-domain inhibitors, such as secretory leukocyte protease inhibitor,
      tick carboxypeptidase inhibitor, and Ascaris carboxypeptidase inhibitor, has
      provided some clues about how two-domain protease inhibitors may fold, that is,
      either by folding each domain autonomously or with one domain assisting in the
      folding of the other. Finally, the recent determination of the structures of the
      major intermediates of protease inhibitors has shed light on the molecular
      mechanisms guiding the oxidative folding of small disulfide-rich proteins.

PMID- 20812860
TI  - Oxidative stress stimulates autophagic flux during ischemia/reperfusion.
AB  - Autophagy is a bulk degradation process in which cytosolic proteins and
      organelles are degraded through lysosomes. To evaluate autophagic flux in cardiac
      myocytes, we generated adenovirus and cardiac-specific transgenic mice harboring
      tandem fluorescent mRFP-GFP-LC3. Starvation significantly increased the number of
      mRFP-GFP-LC3 dots representing both autophagosomes and autolysosomes per cell,
      suggesting that autophagic flux is increased in cardiac myocytes. H(2)O(2)
      significantly increased autophagic flux, which was attenuated in the presence of
      N-2-mercaptopropionyl glycine (MPG), an antioxidant, suggesting that oxidative
      stress stimulates autophagy in cardiac myocytes. Myocardial ischemia/reperfusion
      (I/R) increased both autophagosomes and autolysosomes, thereby increasing
      autophagic flux. Treatment with MPG attenuated I/R-induced increases in oxidative
      stress, autophagic flux, and Beclin-1 expression, accompanied by a decrease in
      the size of myocardial infarction (MI)/area at risk (AAR), suggesting that
      oxidative stress plays an important role in mediating autophagy and myocardial
      injury during I/R. MI/AAR after I/R was significantly reduced in beclin1(+/-)
      mice, whereas beclin1(+/-) mice treated with MPG exhibited no additional
      reduction in the size of MI/AAR after I/R. These results suggest that oxidative
      stress plays an important role in mediating autophagy during I/R, and that
      activation of autophagy through oxidative stress mediates myocardial injury in
      response to I/R in the mouse heart.

PMID- 20812862
TI  - Organic nitrates differentially modulate circulating endothelial progenitor cells
      and endothelial function in patients with symptomatic coronary artery disease.
AB  - Symptomatic coronary artery disease (CAD) is usually treated with organic
      nitrates. Endothelial progenitor cells (EPCs) are a circulating cell population
      participating in vascular homeostasis in a nitric oxide-dependent manner. We
      investigated the effects of the nitric oxide donors isosorbide dinitrate (ISDN)
      and pentaerythritol tetranitrate (PETN) on EPC and endothelial function in
      patients with symptomatic CAD. We randomized 36 patients with angiographically
      proven CAD to treatment with either ISDN (40 mg retarded release orally two times
      per day; n = 18) or PETN (80 mg orally two times per day; n = 18) for 14 days
      (clinical trial number: NCT01030367). PETN treatment substantially increased
      numbers of circulating CD34(+)/KDR(+) EPCs (p = 0.02), whereas no effects were
      observed in patients treated with ISDN. EPC function assessed by formation of
      endothelial colonies was enhanced by twofold (p = 0.04) in patients treated with
      PETN. No changes were observed after ISDN treatment. Endothelial function,
      assessed by peripheral arterial tonometry, remained unchanged during PETN
      treatment, but was significantly impaired in patients treated with ISDN.
      Treatment of symptomatic CAD patients with PETN for 14 days significantly
      increased levels of circulating EPC and improved markers for EPC function,
      whereas ISDN was without effects on EPCs and worsened endothelial function.

PMID- 20812861
TI  - Retinoic acid induces autophagosome maturation through redistribution of the
      cation-independent mannose-6-phosphate receptor.
AB  - Retinoic acids (RAs) have diverse biologic effects and regulate several cellular
      functions. Here, we investigated the role of RA on autophagy by studying its
      effects on autophagosome (AUT) maturation, as well as on upstream regulators of
      autophagosome biogenesis. Our studies, based on the use of pH-sensitive
      fluorescent reporter markers, suggested that RA promotes AUT acidification and
      maturation. By using competitive inhibitors and specific agonists, we
      demonstrated that this effect is not mediated by the classic RAR and RXR
      receptors. RA did not affect the levels of upstream regulators of autophagy, such
      as Beclin-1, phospho-mTOR, and phospho-Akt1, but induced redistribution of both
      endogenous cation-independent mannose-6-phosphate receptor CIMPR and transiently
      transfected GFP and RFP full-length CIMPR fusion proteins from the trans-Golgi
      region to acidified AUT structures. Those structures were found to be amphisomes
      (acidified AUTs) and not autophagolysosomes. The critical role of CIMPR in AUT
      maturation was further demonstrated by siRNA-mediated silencing of endogenous
      CIMPR. Transient CIMPR knockdown resulted in remarkable accumulation of
      nonacidified AUTs, a process that could not be reversed with RA. Our results
      suggest that RA induces AUT acidification and maturation, a process critical in
      the cellular autophagic mechanism.

PMID- 20812863
TI  - Progenitor cells in arteriosclerosis: good or bad guys?
AB  - Accumulating evidence indicates that the mobilization and recruitment of
      circulating or tissue-resident progenitor cells that give rise to endothelial
      cells (ECs) and smooth muscle cells (SMCs) can participate in atherosclerosis,
      neointima hyperplasia after arterial injury, and transplant arteriosclerosis. It
      is believed that endothelial progenitor cells do exist and can repair and
      rejuvenate the arteries under physiologic conditions; however, they may also
      contribute to lesion formation by influencing plaque stability in advanced
      atherosclerotic plaque under specific pathologic conditions. At the same time,
      smooth muscle progenitors, despite their capacity to expedite lesion formation
      during restenosis, may serve to promote atherosclerotic plaque stabilization by
      producing extracellular matrix proteins. This profound evidence provides support
      to the hypothesis that both endothelial and smooth muscle progenitors may act as
      a double-edged sword in the pathogenesis of arteriosclerosis. Therefore, the
      understanding of the regulatory networks that control endothelial and smooth
      muscle progenitor differentiation is undoubtedly fundamental both for basic
      research and for improving current therapeutic avenues for atherosclerosis. We
      update the progress in progenitor cell study related to the development of
      arteriosclerosis, focusing specifically on the role of progenitor cells in lesion
      formation and discuss the controversial issues that regard the origins,
      frequency, and impact of the progenitors in the disease.

PMID- 20812864
TI  - Hydrogen sulfide: neurophysiology and neuropathology.
AB  - Hydrogen sulfide (H(2)S) was known to be a toxic gas and an environmental hazard
      for many decades. However, it is now recognized that H(2)S may serve as a gaseous
      mediator that is endogenously produced to influence biological functions in
      mammalian. Together with nitric oxide and carbon monoxide, it forms the group of
      mediators that has been termed the "gasotransmitters." The past decade has seen
      an exponential growth of scientific interest in the physiological and
      pathological significance of H(2)S especially with respect to its role in the
      central nervous system and the cardiovascular system. In the central nervous
      system, H(2)S facilitates long-term potentiation and regulates intracellular
      calcium concentration and pH level in brain cells. Intriguingly, H(2)S produces
      antioxidant, anti-inflammatory, and antiapoptotic effects that may have relevance
      to neurodegenerative disorders. Abnormal generation and metabolism of H(2)S have
      been reported in the pathogenesis of ischemic stroke, Alzheimer's disease,
      Parkinson's disease, and recurrent febrile seizure. Exogenously applied H(2)S is
      demonstrated to have value for the treatment of febrile seizure and Parkinson's
      disease. This article presents an overview of current knowledge of H(2)S in
      relation to brain functions, with a special emphasis on its neuroprotective
      effects and the underlying cellular and molecular mechanisms.

PMID- 20812865
TI  - Chronic exposure to sulfide causes accelerated degradation of cytochrome c
      oxidase in ethylmalonic encephalopathy.
AB  - Ethylmalonic encephalopathy (EE) is an autosomal recessive, invariably fatal
      disorder associated with mutations in ETHE1, a gene encoding a mitochondrial
      sulfur dioxygenase (SDO). The main consequence of the absence of Ethe1-SDO is the
      accumulation of sulfide (H(2)S) in critical tissues, including colonic mucosa,
      liver, muscle, and brain. To make progress in the elucidation of the biochemical
      mechanisms leading to cytochrome c oxidase (COX) deficiency, we (i) generated
      tissue-specific conditional Ethe1 knockout mice to clarify the different
      contributions of endogenous and exogenous H(2)S production, and (ii) studied the
      development of H(2)S-driven COX deficiency in Ethe1(-/-) mouse tissues and human
      cells. Ethe1(-/-) conditional animals displayed COX deficiency limited to the
      specific targeted tissue. The accumulation of H(2)S over time causes progressive
      COX deficiency in animal tissues and human cells, which is associated with
      reduced amount of COX holoenzyme, and of several COX subunits, including
      mitochondrially encoded cytochrome c oxidase 1 (MTCO1), MTCO2, COX4, and COX5A.
      This reduction is not paralleled by consistent downregulation in expression of
      the corresponding mRNAs. Tissue-specific ablation of Ethe1 causes COX deficiency
      in targeted organs, suggesting that failure in neutralizing endogenous, tissue
      specific production of H(2)S is sufficient to cause the biochemical defect but
      neither to determine a clinical impact nor to induce the biomarker profile
      typical of EE. The mechanism by which H(2)S causes COX deficiency consists of
      rapid heme a inhibition and accelerated long-term degradation of COX subunits.
      However, the pleiotropic devastating effects of H(2)S accumulation in EE cannot
      be fully explained by the sole defect of COX in critical tissues, but are likely
      consequent to several toxic actions on a number of enzymatic activities in
      different tissues, including endothelial lining of the small vessels, leading to
      multiorgan failure.

PMID- 20812866
TI  - Free and acid-labile hydrogen sulfide concentrations in mouse tissues:
      anomalously high free hydrogen sulfide in aortic tissue.
AB  - Endogenously produced hydrogen sulfide is thought to function as an intracellular
      messenger. There is, however, little information on tissue concentrations of free
      hydrogen sulfide, the putative messenger form of this molecule, versus that of
      the bound (acid-labile) form. The present report describes the application of a
      novel technique to measure free and acid-labile hydrogen sulfide in mouse
      tissues. Very low free hydrogen sulfide concentrations (<0.050 MUmol/kg) were
      observed in brain, liver, blood, heart, kidney, striated muscle, and esophagus.
      Aortic concentrations of free hydrogen sulfide were 20 to 100 times greater than
      that of the other tissues. Acid-labile hydrogen sulfide concentrations were
      multiple orders of magnitude greater than that of the free form in every tissue
      other than aorta. Previous reports of tissue hydrogen sulfide concentrations of
      30 to >100 MUmol/kg measured bound rather than free hydrogen sulfide, the
      observation that aorta contains anomalously high free hydrogen sulfide
      concentrations lends support for a vasodilator function for this molecule, and
      the very low free hydrogen sulfide concentrations in most tissues seemingly
      requires intermediation of a yet to be described receptor-like mechanism if this
      molecule is to serve as a gasotransmitter.

PMID- 20812867
TI  - Pathophysiologically relevant levels of hydrogen peroxide induce glutamate
      independent neurodegeneration that involves activation of transient receptor
      potential melastatin 7 channels.
AB  - Stroke/brain ischemia is a leading cause of death and long-term disabilities.
      Increased oxidative stress plays an important role in the pathology of brain
      ischemia. Hydrogen peroxide (H(2)O(2)) is a major oxidant known to cause neuronal
      injury; however, the detailed mechanism remains unclear. Previous studies have
      suggested that H(2)O(2)-induced injury is associated with increased intracellular
      Ca(2+), mediated by glutamate receptors or voltage-gated Ca(2+) channels. Here,
      we demonstrate that, at concentrations relevant to stroke, H(2)O(2) induces a
      Ca(2+)-dependent injury of mouse cortical neurons in the absence of activation of
      these receptors/channels. With the culture medium containing blockers of
      glutamate receptors and voltage-gated Ca(2+) channels, brief exposure of neurons
      to H(2)O(2) induced a dose-dependent injury. Reducing [Ca(2+)](e) inhibited
      whereas increasing [Ca(2+)](e) potentiated the H(2)O(2) injury. Fluorescent
      Ca(2+) imaging confirmed the increase of [Ca(2+)](i) by H(2)O(2) in the presence
      of the blockers of glutamate receptors and voltage-gated Ca(2+) channels.
      Addition of 2-aminoethoxydiphenyl borate, an inhibitor of transient receptor
      potential melastatin 7 (TRPM7) channels, or the use of TRPM7-small interference
      RNA, protected the neurons from H(2)O(2) injury. In contrast, overexpressing
      TRPM7 channels in human embryonic kidney 293 cells increased H(2)O(2) injury. Our
      findings indicate that H(2)O(2) can induce Ca(2+) toxicity independent of
      glutamate receptors and voltage-gated Ca(2+) channels. Activation of TRPM7
      channels is involved in such toxicity.

PMID- 20812870
TI  - Nitric oxide signaling and nitrosative stress in neurons: role for S
      nitrosylation.
AB  - Nitric oxide (NO) mediates cellular signaling pathways that regulate a plethora
      of physiological processes. One of the signaling mechanisms mediated by NO is
      through S-nitrosylation of cysteine residues in target proteins, which is now
      regarded as an important redox-based physiological action. Deregulation of the
      protein S-nitrosylation upon nitrosative stress, however, has also been linked to
      various human diseases, such as neurodegenerative disorders. Between these
      physiological and pathophysiological roles, there are mechanisms whereby a milder
      level of nitrosative stress provides S-nitrosylation of some proteins that
      counteracts the pathological processes, serving as a negative feedback mechanism.
      In addition, NO has recently emerged as a mediator of epigenetic gene expression
      and chromatin changes. In this review, these molecular mechanisms, especially
      those in the central nervous system and neurodegenerative disorders, are
      described.

PMID- 20812869
TI  - Oxidative stress in ischemic brain damage: mechanisms of cell death and potential
      molecular targets for neuroprotection.
AB  - Significant amounts of oxygen free radicals (oxidants) are generated during
      cerebral ischemia/reperfusion, and oxidative stress plays an important role in
      brain damage after stroke. In addition to oxidizing macromolecules, leading to
      cell injury, oxidants are also involved in cell death/survival signal pathways
      and cause mitochondrial dysfunction. Experimental data from laboratory animals
      that either overexpress (transgenic) or are deficient in (knock-out) antioxidant
      proteins, mainly superoxide dismutase, have provided strong evidence of the role
      of oxidative stress in ischemic brain damage. In addition to mitochondria, recent
      reports demonstrate that NADPH oxidase (NOX), an important pro-oxidant enzyme, is
      also involved in the generation of oxidants in the brain after stroke. Inhibition
      of NOX is neuroprotective against cerebral ischemia. We propose that superoxide
      dismutase and NOX activity in the brain is a major determinant for ischemic
      damage/repair and that these major anti- and pro-oxidant enzymes are potential
      endogenous molecular targets for stroke therapy.

PMID- 20812868
TI  - S-nitrosylation of critical protein thiols mediates protein misfolding and
      mitochondrial dysfunction in neurodegenerative diseases.
AB  - Excessive nitrosative and oxidative stress is thought to trigger cellular
      signaling pathways leading to neurodegenerative conditions. Such redox
      dysregulation can result from many cellular events, including hyperactivation of
      the N-methyl-D-aspartate-type glutamate receptor, mitochondrial dysfunction, and
      cellular aging. Recently, we and our colleagues have shown that excessive
      generation of free radicals and related molecules, in particular nitric oxide
      species (NO), can trigger pathological production of misfolded proteins, abnormal
      mitochondrial dynamics (comprised of mitochondrial fission and fusion events),
      and apoptotic pathways in neuronal cells. Emerging evidence suggests that
      excessive NO production can contribute to these pathological processes,
      specifically by S-nitrosylation of specific target proteins. Here, we highlight
      examples of S-nitrosylated proteins that regulate misfolded protein accumulation
      and mitochondrial dynamics. For instance, in models of Parkinson's disease, these
      S-nitrosylation targets include parkin, a ubiquitin E3 ligase and neuroprotective
      molecule, and protein-disulfide isomerase, a chaperone enzyme for nascent protein
      folding. S-Nitrosylation of protein-disulfide isomerase may also be associated
      with mutant Cu/Zn superoxide dismutase toxicity in amyotrophic lateral sclerosis.
      Additionally, in models of Alzheimer's disease, excessive NO generation leads to
      the formation of S-nitrosylated dynamin-related protein 1 (forming SNO-Drp1),
      which contributes to abnormal mitochondrial fragmentation and resultant synaptic
      damage.

PMID- 20812871
TI  - Hair cortisol and the risk for acute myocardial infarction in adult men.
AB  - Acute stress is increasingly recognized as a precipitant of acute myocardial
      infarction (AMI). However, the role of chronic stress in developing AMI is less
      clear. We have developed a method to measure cortisol in hair, which allows
      longitudinal assessment of cortisol levels prior to an acute event. We aimed to
      evaluate the hypothesis that chronic stress, as assessed by hair cortisol
      content, is associated with the development of AMI. A prospective case-control
      study included 56 patients admitted to hospital with AMI and 56 control patients,
      admitted to internal medicine wards for other indications. An enzyme immunoassay
      technique was used to measure cortisol in the most proximal 3 cm of hair,
      considered to represent the most recent 3 months of exposure. Median hair
      cortisol contents (range) were 295.3 (105.4-809.3)ng/g in AMI patients and 224.9
      (76.58-949.9)ng/g in controls (p = 0.006, Mann-Whitney U-test). After controlling
      for other risk factors for AMI using multiple logistic regression, log
      transformed hair cortisol content remained the strongest predictor (OR 17.4, 95%
      CI 2.15-140.5; p = 0.007). We demonstrated elevated hair cortisol concentrations
      in patients with AMI. This suggests that chronic stress, as assessed by increased
      hair cortisol in the 3 months prior to the event, may be a contributing factor
      for AMI.

PMID- 20812872
TI  - Control of redox state and redox signaling by neural antioxidant systems.
AB  - The glutathione/glutathione disulfide (GSH/GSSG) redox pair forms the major redox
      couple in cells and as such plays a critical role in regulating redox-dependent
      cellular functions. Not only does GSH act as an antioxidant but it can also
      modulate the activity of a variety of different proteins. An impairment in GSH
      status is thought to be the precipitating event in a wide range of neurological
      disorders. Therefore, understanding how to maintain GSH in the CNS could provide
      a valuable therapeutic approach. Intracellular GSH levels are regulated by a
      complex series of pathways that include substrate transport and availability,
      rates of synthesis and regeneration, GSH utilization, and GSH efflux. To date,
      the most effective approaches for maintaining GSH levels in the CNS include
      enhancing cyst(e)ine uptake both directly and indirectly via transcriptional
      upregulation of system x(c)(-), increasing GSH synthesis via transcriptional
      upregulation of the rate limiting enzyme in GSH biosynthesis, and decreasing GSH
      utilization. Among the transcription factors that play critical roles in GSH
      metabolism are NF-E2-related factor 2 (Nrf2) and activating transcription factor
      4 (ATF4). Thus, compounds that can upregulate these transcription factors may be
      particularly useful in promoting the functional maintenance of the CNS through
      their effects on GSH metabolism.

PMID- 20812873
TI  - Transcriptome analysis in endothelial progenitor cell biology.
AB  - The use of endothelial progenitor cells (EPCs) is a promising new treatment
      option for cardiovascular diseases. Many of the underlying mechanisms that result
      in an improvement of endothelial function in vivo remain poorly elucidated to
      this date, however. We summarize the current positions and potential applications
      of gene-expression profiling in the field of EPC biology. Based on our own and
      published gene-expression data, we demonstrate that gene-expression profiling can
      efficiently be used to characterize different EPC types. Furthermore, we
      highlight the potential of gene-expression profiling for the analysis of changes
      that EPCs undergo during culture and examine changes in gene transcription in
      diseased patients. Transcriptome profiling is a powerful tool for the
      characterization and functional analysis of EPCs in health and disease.

PMID- 20812875
TI  - Homing of progenitor cells to ischemic tissues.
AB  - Progenitor cells mobilized from the bone marrow are recruited to ischemic tissues
      and increase neovascularization. Cell therapy is a promising new therapeutic
      option for treating patients with ischemic disorders. The efficiency of cell
      therapy to augment recovery after ischemia depends on the sufficient recruitment
      and engraftment of the cells to the target tissue. Homing to sites of active
      neovascularization is a complex process depending on a timely and spatially
      orchestrated interplay between chemokines, chemokine receptors, adhesion
      molecules (selectins and integrins), and intracellular signaling cascades,
      including also oxidative signaling. This review will focus on the homing
      mechanisms of progenitor and stem cells to ischemic tissues. Specifically, we
      discuss the role of chemokines and adhesion molecules such as selectins and
      integrins and the crosstalk between chemokines and integrins in progenitor cell
      homing.

PMID- 20812874
TI  - Redox regulation of the intrinsic pathway in neuronal apoptosis.
AB  - Two principal pathways exist by which cells can undergo apoptotic death, known as
      the extrinsic and the intrinsic pathways. Binding of a ligand to a death receptor
      activates the extrinsic pathway. In the intrinsic pathway, an apoptotic stimulus,
      such as neurotrophin withdrawal or exposure to a toxin, causes a proapoptotic
      member of the Bcl-2 family of proteins, such as Bax, to permeabilize the outer
      mitochondrial membrane. This allows redistribution of cytochrome c from the
      mitochondrial intermembrane space into the cytoplasm, where it causes activation
      of caspase proteases and, subsequently, cell death. A dramatic increase occurs in
      mitochondria-derived reactive oxygen species (ROS) during the apoptotic death of
      sympathetic, cerebellar granule, and cortical neurons. These ROS lie downstream
      of Bax in each cell type. Here I review possible mechanisms by which Bax causes
      increased ROS during neuronal apoptosis. I also discuss evidence that these ROS
      are an important part of the apoptotic cascade in these cells. Finally, I discuss
      evidence that suggests that neurotrophins prevent release of cytochrome c in
      neurons through activation of an antioxidant pathway.

PMID- 20812877
TI  - The inhibitory GABA system as a therapeutic target for cognitive symptoms in
      schizophrenia: investigational agents in the pipeline.
AB  - IMPORTANCE OF THE FIELD: Cognitive impairments associated with schizophrenia
      include neuropsychological deficits in attention, working memory, learning and
      executive function. Because these cognitive deficits precede the onset of
      psychosis, are present in non-affected relatives and constitute the best
      predictor of functional outcome, they are a cardinal clinical feature in
      schizophrenia. Currently, no effective treatment for the cognitive symptoms in
      schizophrenia exists. AREAS COVERED IN THIS REVIEW: There is evidence that the
      inhibitory GABA system is affected in schizophrenia, suggesting that cognitive
      impairments associated with schizophrenia may be effectively treated by drugs
      that modulate the GABA(A) receptor. However, classical benzodiazepines produce
      cognitive impairments and are associated with numerous side effects. The recent
      development of compounds with selective efficacy for different alpha subunits at
      the benzodiazepine site of the GABA(A) receptor has renewed interest for the
      therapeutic potential of GABAergic drugs. WHAT THE READER WILL GAIN: This review
      summarizes the involvement of the inhibitory GABA system in the cognitive
      abnormalities of schizophrenia and discusses putative (selective) GABAergic
      cognition-enhancing drugs for schizophrenia. TAKE HOME MESSAGE: If cognitive
      abnormalities in schizophrenic individuals are the result of GABAergic
      dysfunction, selectively modulating the GABA system could comprise a promising
      therapeutic intervention for cognitive symptoms in schizophrenia.

PMID- 20812876
TI  - Redox biology: computational approaches to the investigation of functional
      cysteine residues.
AB  - Cysteine (Cys) residues serve many functions, such as catalysis, stabilization of
      protein structure through disulfides, metal binding, and regulation of protein
      function. Cys residues are also subject to numerous post-translational
      modifications. In recent years, various computational tools aiming at classifying
      and predicting different functional categories of Cys have been developed,
      particularly for structural and catalytic Cys. On the other hand, given
      complexity of the subject, bioinformatics approaches have been less successful
      for the investigation of regulatory Cys sites. In this review, we introduce
      different functional categories of Cys residues. For each category, an overview
      of state-of-the-art bioinformatics methods and tools is provided, along with
      examples of successful applications and potential limitations associated with
      each approach. Finally, we discuss Cys-based redox switches, which modify the
      view of distinct functional categories of Cys in proteins.

PMID- 20812878
TI  - Aliskiren: beyond blood pressure reduction.
AB  - IMPORTANCE OF THE FIELD: Hypertension is one of the most important risk factors
      and causes of cardiovascular disease (CVD). From some years, renin-angiotensin
      aldosterone system (RAAS) inhibitors such angiotensin converting enzyme (ACE) and
      angiotensin receptor blockade (ARB) have been of interest, not only for better
      blood pressure (BP) control but also for their involvement in the mechanisms of
      various organ functions. AREAS COVERED IN THIS REVIEW: The aim of this review is
      to focus on the effectiveness and safety of aliskiren beyond the treatment of
      hypertension. WHAT THE READER WILL GAIN: Aliskiren, the first approved renin
      inhibitor to reach the market, is a low-molecular-weight, orally active,
      hydrophilic non-peptide molecule that blocks angiotensin I generation. Because of
      its mechanism of action, aliskiren may offer the additional opportunity to
      inhibit progression of atherosclerosis at tissue level and the potential to be
      useful in a wide spectrum of conditions. However, we will discuss how it might
      become a reasonable therapeutic choice also in a broad number of clinical
      conditions, sharing an increased cardiovascular risk as stable coronary artery
      disease (CAD), microvascular and cardio-renal disease, diabetes, and peripheral
      arterial disease (PAD). TAKE HOME MESSAGE: Therapy of hypertension through a
      better blockade of RAAS may be the first step in also achieving interesting
      results in the complications that hypertension causes in several organs.

PMID- 20812879
TI  - Treatment response to pregabalin in fibromyalgia pain: effect of patient baseline
      characteristics.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of patients'
      characteristics at baseline on the magnitude of pain response to pregabalin in
      patients with fibromyalgia. METHODS: Data from four randomized, multicenter,
      placebo-controlled clinical studies of pregabalin in patients with fibromyalgia
      were used for the analysis. Approved doses (300 and 450 mg/day) were pooled to
      enhance the sensitivity of the interaction tests. A centered covariate
      interaction model was used to assess the treatment effects; a noncentered model
      was used for estimated mean pain changes and least square means across different
      levels of baseline covariates. The interaction was considered significant if p <
      0.10. RESULTS: In total, 2061 patients (median age, 49 years; median pain score,
      7.0; median duration of fibromyalgia, 83 months) were included in this analysis.
      No significant interaction was observed between treatment and anxiety,
      depression, or duration of fibromyalgia. Significant treatment by baseline mean
      pain (p = 0.037), treatment by baseline sleep score (p = 0.071), and treatment by
      age (p = 0.051) interactions were observed. CONCLUSION: The magnitude of response
      to pregabalin in terms of changes in pain may depend on age, pain, and sleep
      levels at baseline in patients with fibromyalgia.

PMID- 20812880
TI  - The search of a genetic basis for noise-induced hearing loss (NIHL).
AB  - BACKGROUND AND AIM: Knowledge about the genetic factors responsible for noise
      induced hearing loss (NIHL) is still limited. This study investigated whether
      genetic factors are associated or not to susceptibility to NIHL. SUBJECTS AND
      METHODS: The family history and genotypes were studied for candidate genes in 107
      individuals with NIHL, 44 with other causes of hearing impairment and 104
      controls. Mutations frequently found among deaf individuals were investigated
      (35delG, 167delT in GJB2, Delta(GJB6- D13S1830), Delta(GJB6- D13S1854) in GJB6
      and A1555G in MT-RNR1 genes); allelic and genotypic frequencies were also
      determined at the SNP rs877098 in DFNB1, of deletions of GSTM1 and GSTT1 and
      sequence variants in both MTRNR1 and MTTS1 genes, as well as mitochondrial
      haplogroups. RESULTS: When those with NIHL were compared with the control group,
      a significant increase was detected in the number of relatives affected by
      hearing impairment, of the genotype corresponding to the presence of both GSTM1
      and GSTT1 enzymes and of cases with mitochondrial haplogroup L1. CONCLUSION: The
      findings suggest effects of familial history of hearing loss, of GSTT1 and GSTM1
      enzymes and of mitochondrial haplogroup L1 on the risk of NIHL. This study also
      described novel sequence variants of MTRNR1 and MTTS1 genes.

PMID- 20812881
TI  - Prevalence of under-nutrition and its correlates among under 3 year-old children
      in rural areas of Andhra Pradesh, India.
AB  - BACKGROUND: Under-nutrition continues to be a major public health problem,
      especially among young children in India. The present study was undertaken to
      assess the nutritional status of under-3 year-old children and factors associated
      with under-nutrition. METHOD: A community-based cross-sectional survey was
      carried out in 40 Anganwadi centre villages of Medak district of Andhra Pradesh,
      India. A total of 805 children were selected for nutritional assessment in terms
      of under-weight, stunting and wasting using the new WHO growth standards. Wealth
      index was calculated using principal components analysis. A conceptual
      hierarchical framework was used as a basis for controlling for the explanatory
      factors in multivariate analysis. RESULTS: Prevalence of under-weight, stunting
      and wasting was ~39%, 30% and 22%, respectively. The risk of under-weight and
      stunting was 1.80- and 3.02-times higher among 12-23 months and 3.13- and 5.50
      times higher among 24-36 months children as compared to children under 12 months,
      respectively. The risk of under-weight was 2.74- and 1.73-times higher among
      children belonging to the lowest and middle household wealth index, respectively.
      CONCLUSIONS: Under-nutrition is a significant public health problem among under 3
      year-old children. The prevalence of under-nutrition was significantly higher
      among boys and those belonging to the lowest and middle wealth index. Thus,
      implementation of appropriate nutritional intervention strategies and improvement
      in household socio-economic condition may help in improving nutritional status.

PMID- 20812882
TI  - Age and secular effects on muscular strength of indigenous rural adults in
      Oaxaca, Southern Mexico: 1978-2000.
AB  - PURPOSE: To evaluate age and secular changes in strength of rural Zapotec adults
      in Oaxaca between 1978 and 2000. METHODS: Grip strength, height and weight were
      measured in 1978 (n = 247, 19-82 years) and 2000 (n = 407, 19-89 years); 35 males
      and 52 females were measured in both years. MANCOVA was used for comparisons by
      age and year. RESULTS: Grip strength and strength/height decline with age; the
      slope is greater after 40-49 years. Both are significantly greater in 2000
      compared to 1978 only in males 19-29 and 30-39 years and in females 30-39 years.
      Strength and strength/height decline at a slightly faster rate in females than
      males during young adulthood, but at similar rates in both sexes during middle
      age. Strength/mass is greater in 1978 than 2000, but differences are not
      significant in most age groups. Strength/mass declines linearly with age and
      rates do not differ between young and older adults of both sexes. Left grip
      strength/left mid-arm muscle circumference shows a pattern across age similar to
      strength/mass in both sexes. CONCLUSION: Grip strength and strength per unit size
      declined with age. Strength and strength/height tended to increase between 1978
      and 2000, while the opposite occurred for strength/weight. Results likely
      reflected in changes in habitual physical activity patterns associated with the
      transition from subsistence agriculture to less economic dependence upon
      agriculture.

PMID- 20812883
TI  - Anthropological features of the CFTR gene: Its variability in an African
      population.
AB  - BACKGROUND: The CFTR gene (Cystic Fibrosis conductance Transmembrane Regulator)
      is the gene responsible for Cystic Fibrosis, the most common severe autosomal
      recessive disease in Europeans. It has been extensively explored in several
      European and European-derived populations, but poorly studied in the other major
      human groups. AIM: To characterize the variability of the CFTR gene in an African
      population. SUBJECTS AND METHODS: Using DGGE, all 27 exons (4443 bp) and 2184 bp
      of the flanking intronic regions of the CFTR gene were studied in a random sample
      of 45 Mossi from Burkina Faso (Western sub-Saharan Africa). RESULTS: Sixteen
      variable sites were found: 13 SNPs (one in the promoter region, four non
      synonymous and five synonymous in the exons and three in the introns) and three
      intronic STRs. Only the promoter site ( - 94 G/T), slightly polymorphic in the
      present survey, was not variable in different European populations. Comparison
      between Western Africans, Eastern Africans, Europeans and Eastern Asians showed
      that alleles at two intronic STRs (T(n) and (TG)(m) in intron 8), four exonic
      (M470V, 2694 T/G, 4002 A/G and 4521 G/A) and one intronic (875+40 A/G) SNPs have
      very different frequencies among at least two major human groups. Moreover, the
      overall degree of non-synonymous variability in Mossi is much lower than that in
      Europeans. A possible interpretation of this finding is proposed. CONCLUSIONS:
      The CFTR gene has been since long hypothesized to have undergone selection in
      Europeans. The present study by comparing Africans and Europeans for the overall
      variability of the gene supports this hypothesis.

PMID- 20812884
TI  - Nutritional and socioeconomic status in cognitive development of Santal children
      of Purulia district, India.
AB  - BACKGROUND: Cognitive development of children depends on nutritional and
      socioeconomic factors. OBJECTIVES: The objectives of the present study were to
      assess the cognitive development and to investigate the relationship of
      nutritional and socioeconomic status (SES) to cognitive development in 5-12 year
      old Santal children of Purulia district of West Bengal, India. METHODS: The
      nutritional status of each child was assessed by z-score of height-for-age,
      weight-for-height and weight-for-age parameters. SES was measured using the
      updated Kuppusswami scale. Cognitive development was measured by Raven's Coloured
      Progressive Matrices (RCPM). RESULTS: The growth curve of RCPM scores of Santal
      children remained around the 5(th) percentile values of British children. The
      RCPM scores of the adequately nourished children and upper-lower SES were
      significantly higher (p < 0.05) than the children with lower SES and nutritional
      status. About 42.96% and 27.69% of Santal children were found to be in the
      intellectually deficient and below average groups, respectively. RCPM scores of
      Santal children were significantly correlated with nutritional status and
      socioeconomic factors (p < 0.01). CONCLUSION: The surveyed children showed poor
      cognitive functions. The vulnerable nutritional and socioeconomic statuses of
      Santal children are the major causes for their poor cognitive development.

PMID- 20812885
TI  - Emerging therapies for cystic fibrosis lung disease.
AB  - IMPORTANCE OF THE FIELD: Cystic fibrosis (CF), one of the major respiratory
      diseases, is caused by mutations in a gene encoding for a chloride channel.
      Abnormal transepithelial ion transport leads to a reduced volume of the airway
      surface liquid layer and reduced mucociliary clearance. AREAS COVERED IN THIS
      REVIEW: There is currently no cure for CF and CF lung disease remains a major
      contributor to morbidity and mortality. However, most current treatments for CF
      lung disease do not address the underlying pathology. We describe here new
      therapeutic developments aiming to identify or generate compounds that counteract
      the effects of cystic fibrosis transmembrane conductance regulator (CFTR) on the
      airway. WHAT THE READER WILL GAIN: This review summarizes the current state of
      new developments in the treatment of CF lung disease. These drugs include
      nebulized and inhaled osmotically active agents, but also modifiers of ion
      channels other than CFTR, such as activators of alternative chloride channels or
      inhibitors of sodium absorption, and compounds in development aim to correct or
      improve impaired CFTR function directly. First clinical trials with new drugs
      including ion channel modifiers and CFTR pharmacotherapeutics have revealed very
      promising results. TAKE HOME MESSAGE: CF drug therapy is moving rapidly from
      symptomatic therapy to treatment of the underlying pathophysiology.

PMID- 20812886
TI  - Regional presentation of hepatic diseases: CT and MR imaging findings of
      differential diagnosis.
AB  - Neoplastic and nonneoplastic diseases may involve the liver with a regional
      distribution, which is defined as a non-focal process without any specific
      anatomic predilection. In this pictorial essay we review hepatic diseases
      commonly presenting with a regional distribution in the liver and describe the CT
      and MR imaging findings helpful for differential diagnosis. Knowledge of the
      characteristic imaging manifestations of neoplastic and non-neoplastic diseases
      affecting the liver regionally will facilitate an accurate diagnosis and result
      in the appropriate clinical management of these liver diseases.

PMID- 20812887
TI  - Advance care planning for patients with ALS: feasibility of an interactive
      computer program.
AB  - This pilot study examined whether an interactive, computer based decision aid can
      help patients with amyotrophic lateral sclerosis (ALS) engage in effective
      advance care planning. Individuals being treated for ALS (>18 years old, English
      speaking, and without dementia) were recruited to use a decision aid and complete
      pre-/post-intervention measures. Seventeen individuals completed the pre
      intervention questionnaires and decision aid; 16/17 (94%) completed the post
      intervention measures, and none reported any burden from the intervention.
      'Overall satisfaction' with the decision aid was very high (mean = 8.5 +/- 0.27:
      1 = not at all satisfied, 10 = extremely satisfied), as was 'perceived accuracy'
      of the computer generated advance directive in reflecting patients' wishes (mean
      = 8.6 +/- 0.27: 1 = not at all accurate, 10 = extremely accurate). Participants
      judged the 'amount of information' provided by the intervention appropriate (mean
      = 6.8 +/- 0.38: 1 = too little, 5 = about right, 10 = too much), and on a
      detailed, 12-item assessment judged the decision aid very positively (mean = 4.16
      +/- 0.16: 1 = very dissatisfied, 5 = very satisfied). The intervention prompted
      many participants to discuss advance care planning with loved ones and to share
      their computer generated advance directive with their physician. This study
      demonstrates that individuals with ALS can successfully complete a computer based
      decision aid for advance care planning, and suggests that this intervention can
      help promote effective advance care planning.

PMID- 20812889
TI  - Equivalent threshold sound pressure levels (ETSPL) for Interacoustics DD 45 supra
      aural audiometric earphones.
AB  - This paper describes the determination and results of pure-tone equivalent
      threshold sound pressure levels for the Interacoustics DD 45 audiometric earphone
      equipped with standard Model 51 cushions. The size and shape of the DD 45
      transducer resembles the classic Telephonics TDH 39 earphone. Pure-tone hearing
      threshold measurements were performed for both ears of 29 test subjects. All
      audiometric frequencies from 125 to 8000 Hz were used. The data are intended for
      inclusion in future standardized reference equivalent threshold sound pressure
      levels. The results show that the DD 45 may be a good substitute for the THD 39
      without the traditional 5-dB problem at 6000 Hz.

PMID- 20812888
TI  - No evidence of microbleeds in ALS patients at 7 Tesla MRI.
AB  - There have been several reports about disruption of the blood-spinal cord barrier
      (BSCB) and blood-brain barrier (BBB) in SOD1 mutant mice. Pathologically,
      microbleeds and hemosiderine deposits were found. We investigated patients with
      ALS for the occurrence of cerebral microbleeds with 7 Tesla MRI. Twelve patients
      with ALS and 12 age- and sex-matched healthy controls were studied. We performed
      T2*-weighed imaging which enables whole-brain in vivo detection of cerebral
      microbleeds and hemosiderin deposits in humans. No microbleeds were found in
      patients with ALS.

PMID- 20812890
TI  - Validity and reliability of in-situ air conduction thresholds measured through
      hearing aids coupled to closed and open instant-fit tips.
AB  - Audiometric measurements through a hearing aid ('in-situ') may facilitate
      provision of hearing services where these are limited. This study investigated
      the validity and reliability of in-situ air conduction hearing thresholds
      measured with closed and open domes relative to thresholds measured with insert
      earphones, and explored sources of variability in the measures. Twenty-four
      adults with sensorineural hearing impairment attended two sessions in which
      thresholds and real-ear-to-dial-difference (REDD) values were measured. Without
      correction, significantly higher low-frequency thresholds in dB HL were measured
      in-situ than with insert earphones. Differences were due predominantly to
      differences in ear canal SPL, as measured with the REDD, which were attributed to
      leaking low-frequency energy. Test-retest data yielded higher variability with
      the closed dome coupling due to inconsistent seals achieved with this tip. For
      all three conditions, inter-participant variability in the REDD values was
      greater than intra-participant variability. Overall, in-situ audiometry is as
      valid and reliable as conventional audiometry provided appropriate REDD
      corrections are made and ambient sound in the test environment is controlled.

PMID- 20812893
TI  - Asthma increase among farmers: a 12-year follow-up.
AB  - Respiratory disease is a well known health hazard for farmers, but the long-term
      prognosis is less well known. This is a 12-year follow-up of an investigation of
      Swedish farmers, most of them dairy farmers. A questionnaire was mailed to all
      418 farmers who were alive of the farmers originally participating in 1982. They
      were invited to an interview, spirometry, and blood sampling. Ninety-one per cent
      (380) of the farmers, 321 men and 59 women, responded to the questionnaire. The
      mean age was 56 years for the men and 55 years for the women. Of the group, 10%
      were smokers, 25% ex-smokers, and 65% had never smoked. The population estimate
      for asthma in the farmers was 8.9% in 1994 compared to 2% in 1982, and to 5.4%
      6.6% in the general population in the region in 1982. Of the asthmatic subjects,
      one-third had positive RAST tests (radioallergosorbent tests). Almost 90% of the
      new onset asthma cases since 1982 had non-IgE-mediated asthma. Most of the IgE
      mediated asthmatics had had symptoms for many years, while 70% of the non-IgE
      mediated asthmatic farmers had no or only wheezing with colds 1982. Two new cases
      of hypersensitivity pneumonitis were identified, and 7.3% had experienced
      inhalation fever during the last 12 years. In general, individuals with asthma
      and chronic bronchitis who had left farming were in better health in 1994 as
      compared to 1982. In conclusion, farmers have an enhanced risk to develop asthma
      increasing with age. Asthma in farmers is often non-IgE-mediated.

PMID- 20812895
TI  - Recent FDA approvals and changes.

PMID- 20812894
TI  - Identification and genetic characterization of a novel CRF22_01A1 recombinant
      form of HIV type 1 in Cameroon.
AB  - Cameroon is a country in West Central Africa in which all four groups of HIV-1
      (M, N, O, and P), some circulating recombinant forms (CRFs) and unique
      recombinant forms (URFs) are prevalent. The CRF22 was initially identified
      through a novel URF strain, 01CM53122, and later defined from two additional
      sequences; however, the genomic properties of CRF22 have never been demonstrated
      in detail. In this study, we describe the characterization of five CRF22_01A1
      strains, 02CMLT72, 01CM1867LE, 01CM001BBY, 02CM3097MN, and 02CM1917LE, identified
      in Cameroon without apparent epidemiological links. A typical CRF22_01A1 strain
      contains five fragments that can be assigned to the CRF01_AE and subsubtype A1
      radiations. Forty-eight percent of the genome is classified as CRF01_AE, spanning
      the entire region of the gag gene, part of the pol gene, and accessory genes as
      well as the beginning and the end of the env gene and nef gene. Fifty-two percent
      of the genome is subsubtype A1 including regions mostly in the pol, vif, and env
      genes. The five CRF22_01A1 viruses formed a deep branch outside the groups of
      CRF01_AE and displayed similar mosaic structure but were moderately different
      from the original strain of CRF22_01A1, 01CM53122. Further analysis of the
      01CM53122 genome showed that this virus represents a diverse set of mosaic
      genomes from CRF22_01A1, including a 446-nt segment of 01CM53122 in the env
      region, but unlike other CRF22 strains, clustered with CRF01_AE rather than the
      A1 sequence, suggesting that the 01CM53122 strain is a recombinant of CRF22_01A1
      and CRF01_AE.

PMID- 20812891
TI  - Emerging Bcl-2 inhibitors for the treatment of cancer.
AB  - INTRODUCTION: Bcl-2 family proteins are a component of the antiapoptotic
      machinery and are overexpressed in different malignancies. Accordingly, their
      enhanced expression has been attributed to the observed chemoresistance in most
      of the cancers. Therefore, targeting Bcl-2 family members becomes an important
      and attractive approach towards cancer therapy and is currently a very rapidly
      evolving area of research. This article highlights the numerous advancements that
      have been made in the design and synthesis of small molecule inhibitors (SMI) of
      pro-survival Bcl-2 proteins. AREAS COVERED: This review comprehensively describes
      the progress made over the last 2 decades on this subject, including the clinical
      status of SMIs of Bcl-2 family proteins. Newer insights on the status of our
      knowledge on SMIs of Bcl-2 family proteins, their most beneficial application as
      well as current and future directions in this field are discussed. EXPERT
      OPINION: Targeting Bcl-2 family proteins using SMI strategies is gaining
      momentum, with the emergence of certain new classes of inhibitors in Phase I and
      II clinical settings. In view of the tremendous progress toward the development
      of such inhibitors, this innovative approach certainly holds promise and has the
      potential to become a future mainstay for cancer therapy. The stage is set for
      the next generation of SMIs, for not only Bcl-2 proteins but also for Mcl-1.
      Other emerging molecules in the apoptotic machinery will also be explored and
      targeted.

PMID- 20812896
TI  - Clinical trial will investigate HPV microbicide.

PMID- 20812897
TI  - Not science fiction: undergraduates productive in research.

PMID- 20812898
TI  - Recent advances in regulatory T cell therapy of autoimmunity, graft rejection and
      cancer.
AB  - Since their initial discovery in the 1970s and their subsequent resurgence in the
      mid 1990s, regulatory T (Treg) cells have become one of the most studied cell
      subsets. Treg cells prevent autoimmunity and limit aggressive immune responses
      directed against either pathogen or foreign antigen that might serve to damage
      host tissue. In contrast, tumour cells have been shown to recruit and/or induce
      Treg cells, which can impair tumour immunity. The immunoregulatory function of
      these cells makes them ideal therapeutic candidates for the treatment of
      autoimmune disease and in the prevention of transplant rejection. Likewise,
      depletion of Treg cells remains an additional option in the treatment of cancer.
      Despite significant advances in the treatment of murine models of disease with
      Treg cells, it has been difficult to transfer this success into the clinic. In
      this review, we will discuss relevant patents and the most recent advances in the
      use of Treg cells to treat autoimmunity, prevent graft rejection as well as the
      use of antibodies to deplete these cells in cancer.

PMID- 20812899
TI  - Innovations in siRNA research: a technology comes of age.
AB  - Short interfering RNAs, or siRNAs, belong to a class of RNA species which play a
      role in both cellular defence and gene regulation. siRNAs comprise a larger
      portion of the RNA interference pathway that includes the degradation of RNAs
      which possess complementarily to specific target sequences. This property has
      given siRNA technology the potential to become a powerful new tool for a wide
      variety of disciplines, ranging from the design of novel anti-cancer agents to
      applications in agriculture. The following review outlines patents that have been
      issued over the past 6 months concerning siRNA technology. Patents are discussed
      which encompass improved delivery systems for cellular uptake of siRNAs, new
      therapeutics to combat human diseases, and unique uses of siRNAs to advance plant
      science. The review also provides detailed lists of the most recent patents that
      have been issued which cover these areas of siRNA technology, and paves the way
      for future innovations based on RNA interference in the life sciences.

PMID- 20812901
TI  - Combination therapy with arsenic trioxide for hematological malignancies.
AB  - Arsenic trioxide (ATO) has shown great promise in the treatment of patients with
      relapsed or refractory acute promyelocytic leukemia (APL). However, the
      risk/benefit ratios of ATO in hematologic malignancies other than APL are still
      unclear. In this review, the author attempts to provide current experimental and
      clinical challenges to gain more knowledge of the effects of ATO by examining
      combination therapies with other agents, especially for non-APL hematologic
      malignancies, such as acute myeloid leukemia (AML), acute lymphoid leukemia
      (ALL), chronic myeloid leukemia (CML), chronic lymphoid leukemia (CLL) and
      multiple myeloma (MM). The drugs combined with ATO can be roughly classified into
      (1) signaling inhibitors (imatinib, PD184352, LY294002, 17-Allylamino-17
      demethoxygeldanamycin: 17-AAG), (2) oxidative stress pathway modulators (ascorbic
      acid, 2-methoxyestradiol: 2-ME, dl-buthionine-[S,R]-sulfoximine: BSO), (3) a
      chemotherapeutic drug (melphalan) and (4) others (bortezomib, ATRA). Some of
      these combination therapies have shown promising results in MM not only at the
      experimental level but also at the clinical level. However, studies are still
      ongoing for other non-APL hematologic malignancies. Since ATO is well tolerated
      and its toxicities are manageable and reversible, cell type-specific and
      efficient combination therapies with ATO are advantageous for non-APL
      hematological malignancies and should be developed in the near future.

PMID- 20812900
TI  - Updates of mTOR inhibitors.
AB  - Mammalian target of rapamycin (mTOR) is a central controller of cell growth,
      proliferation, metabolism and angiogenesis. mTOR signaling is often dysregulated
      in various human diseases and thus attracts great interest in developing drugs
      that target mTOR. Currently it is known that mTOR functions as two complexes,
      mTOR complex 1/2 (mTORC1/2). Rapamycin and its analogs (all termed rapalogs)
      first form a complex with the intracellular receptor FK506 binding protein 12
      (FKBP12) and then bind a domain separated from the catalytic site of mTOR,
      blocking mTOR function. Rapalogs are selective for mTORC1 and effective as
      anticancer agents in various preclinical models. In clinical trials, rapalogs
      have demonstrated efficacy against certain types of cancer. Recently, a new
      generation of mTOR inhibitors, which compete with ATP in the catalytic site of
      mTOR and inhibit both mTORC1 and mTORC2 with a high degree of selectivity, have
      been developed. Besides, some natural products, such as epigallocatechin gallate
      (EGCG), caffeine, curcumin and resveratrol, have been found to inhibit mTOR as
      well. Here, we summarize the current findings regarding mTOR signaling pathway
      and review the updated data about mTOR inhibitors as anticancer agents.

PMID- 20812903
TI  - A new twist in cellular resistance to the anticancer drug bleomycin-A5.
AB  - Bleomycin is a potent chemotherapeutic agent that can mediate cell killing by
      attacking the DNA. It is used in combination with other antineoplastic agents to
      effectively treat lymphomas, testicular carcinomas and squamous cell carcinomas
      of the cervix, head and neck. However, resistance to bleomycin remains a
      persistent limitation in exploiting the full therapeutic benefit of the drug for
      other types of cancers. Herein, we review recent findings from both yeast and
      human cells showing that uptake of bleomycin-A5 is a key mechanism that limits
      toxicity of the drug. We also discuss how the mammalian transporter hCT2
      (SLC22A16) could be used to predict the outcome of tumor responses towards
      bleomycin therapy, and highlight the importance of further exploring this
      permease with respect to its regulation and pharmacological substrates for
      treating a wide range of cancers.

PMID- 20812904
TI  - Interaction of tyrosine kinase inhibitors with the MDR- related ABC transporter
      proteins.
AB  - Tyrosine kinase inhibitors (TKIs) are a new class of highly-selective and
      molecularly targeted anticancer agents. Most of these newly developed TKIs are
      hydrophobic, thus allowing them to rapidly penetrate the cell membrane to reach
      their specific intracellular targets. However, their therapeutic potential could
      be significantly hindered by the overexpression of certain ATP binding cassette
      (ABC) membrane transporters, which extrude hydrophobic drugs and result in
      cellular resistance to TKIs by tumor cells. Moreover, it has been recently
      demonstrated that some TKIs could upregulate ABC transporters in tumor cells,
      thereby effectively reducing their intracellular accumulation and antitumor
      efficacy. On the other hand, other TKIs were found to interact with ABC
      transporters and reverse multi-drug resistance (MDR) of tumor cells. In this
      review, the interaction of several TKIs, currently in clinical use or being
      developed in clinical trials, with the MDR-related ABC transporters, in
      particular ABCB1, ABCC1 and ABCG2, will be discussed.

PMID- 20812902
TI  - Structure and function of the human breast cancer resistance protein
      (BCRP/ABCG2).
AB  - The human breast cancer resistance protein (BCRP/ABCG2) is the second member of
      the G subfamily of the large ATP-binding cassette (ABC) transporter superfamily.
      BCRP was initially discovered in multidrug resistant breast cancer cell lines
      where it confers resistance to chemotherapeutic agents such as mitoxantrone,
      topotecan and methotrexate by extruding these compounds out of the cell. BCRP is
      capable of transporting non-chemotherapy drugs and xenobiotiocs as well,
      including nitrofurantoin, prazosin, glyburide, and 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine. BCRP is frequently detected at high levels in stem
      cells, likely providing xenobiotic protection. BCRP is also highly expressed in
      normal human tissues including the small intestine, liver, brain endothelium, and
      placenta. Therefore, BCRP has been increasingly recognized for its important role
      in the absorption, elimination, and tissue distribution of drugs and xenobiotics.
      At present, little is known about the transport mechanism of BCRP, particularly
      how it recognizes and transports a large number of structurally and chemically
      unrelated drugs and xenobiotics. Here, we review current knowledge of structure
      and function of this medically important ABC efflux drug transporter.

PMID- 20812905
TI  - p38 MAP kinase inhibitors as potential therapeutic drugs for neural diseases.
AB  - Mammalian p38 mitogen-activated protein kinases (MAPKs) are activated by various
      cellular stresses, as well as in response to inflammatory cytokines. In the
      central nervous systems (CNS), activation of the p38 MAPK pathway constitutes a
      key step in the development of several diseases, and the molecular mechanisms
      mediated by p38 MAPK signaling have been defined. Activation of this cascade
      releases pro-inflammatory cytokines that are known to be involved in cerebral
      ischemia, Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis
      (MS), neuropathic pain and depression. In AD, stimulated p38 MAPK may trigger the
      hyperphosphorylation of a neural microtubule-associated protein, tau. In
      addition, we have recently revealed that activation of p38 MAPK signaling
      decreases dendritic spine number, which may be associated with memory impairment
      after epileptic seizures. Thus, p38 MAPK can serve as a target for novel drug
      development for neural diseases. p38 MAPK inhibitors have been studied
      extensively in both preclinical experiments and clinical trials for inflammatory
      diseases. New p38 MAPK inhibitors are now being tested in phase II clinical
      trials for neuropathic pain and depression. Here, we review current and possible
      future applications of p38 MAPK inhibitors as therapeutic agents in neural
      diseases.

PMID- 20812906
TI  - Use of STAT1 inhibitors in the treatment of brain I/R injury and
      neurodegenerative diseases.
AB  - In the etiology of brain injury associated to ischemia/reperfusion (I/R) and
      neurodegenerative diseases, a critical involvement of excessive activation of
      signal transducer and activator of transcription 1 (STAT1) and successive
      induction of iNOS expression has widely been evidenced. Any compound capable to
      down-regulate STAT1 activation seems to represent a new, promising anti
      inflammatory drug. Among plant compounds, only a few have shown to possess anti
      STAT1 activity. Among them, epigallocatechin-3-gallate (EGCG), the main
      polyphenol present in green tea leaves, efficiently protects heart from I/R
      injury and this action is strictly correlated to its anti-STAT1 property.
      Hyperforin, the non-polyphenolic compound present in St. John's wort, attenuates
      &beta;-cell death induced by interferon-&gamma; (IFN-&gamma;) by strongly down
      regulating STAT1 activation. STAT1, therefore, seems to represent a new molecular
      target of the protective treatment also against brain injury associated to a
      number of brain pathologies. Either understanding the molecular mechanism of anti
      STAT1 action of these compounds or identification of other anti-STAT1 compounds
      are urged.

PMID- 20812907
TI  - Generalizing moving averages for tiling arrays using combined p-value statistics.
AB  - High density tiling arrays are an effective strategy for genome-wide
      identification of transcription factor binding regions. Sliding window methods
      that calculate moving averages of log ratios or t-statistics have been useful for
      the analysis of tiling array data. Here, we present a method that generalizes the
      moving average approach to evaluate sliding windows of p-values by using combined
      p-value statistics. In particular, the combined p-value framework can be useful
      in situations when taking averages of the corresponding test-statistic for the
      hypothesis may not be appropriate or when it is difficult to assess the
      significance of these averages. We exhibit the strengths of the combined p-values
      methods on Drosophila tiling array data and assess their ability to predict
      genomic regions enriched for transcription factor binding. The predictions are
      evaluated based on their proximity to target genes and their enrichment of known
      transcription factor binding sites. We also present an application for the
      generalization of the moving average based on integrating two different tiling
      array experiments.

PMID- 20812909
TI  - Granger causality analysis of human cell-cycle gene expression profiles.
AB  - Granger causality (GC) tests are ideally suited to investigate time series data
      generated by bivariate vector autoregressive (VAR) processes. Recent studies have
      applied GC analysis and its extensions for modeling functional relationships and
      network structure from temporal gene expression profiles. The present study
      investigates GC analysis of human cell-cycle gene expression profiles that can be
      modeled as a first-order bivariate VAR. Analytical results presented establish
      the contribution of the VAR process parameters, including auto-regulatory
      feedback and noise variance to the mean-squared forecast error, as a critical
      component in identifying statistically significant GC relationships. These
      results in turn discourage blind inference of functional relationship between a
      given pair of genes solely based on the result of the statistical tests for GC.
      The presence of significant auto-regulatory feedback and discrepancy in noise
      variance is demonstrated across the cell-cycle gene expression profiles by VAR
      parameter estimation. It is emphasized that discrepancies in noise variance can
      be due to artifacts and can lead to spurious existence of functional relationship
      between a given pair of genes. VAR parameter estimation is encouraged for better
      of GC interpretation of the results. Published case studies on GC analysis of the
      same publicly available cell-cycle gene expression data are reinvestigated for
      transparency.

PMID- 20812908
TI  - Lasso logistic regression, GSoft and the cyclic coordinate descent algorithm:
      application to gene expression data.
AB  - Statistical methods generating sparse models are of great value in the gene
      expression field, where the number of covariates (genes) under study moves about
      the thousands while the sample sizes seldom reach a hundred of individuals. For
      phenotype classification, we propose different lasso logistic regression
      approaches with specific penalizations for each gene. These methods are based on
      a generalized soft-threshold (GSoft) estimator. We also show that a recent
      algorithm for convex optimization, namely, the cyclic coordinate descent (CCD)
      algorithm, provides with a way to solve the optimization problem significantly
      faster than with other competing methods. Viewing GSoft as an iterative
      thresholding procedure allows us to get the asymptotic properties of the
      resulting estimates in a straightforward manner. Results are obtained for
      simulated and real data. The leukemia and colon datasets are commonly used to
      evaluate new statistical approaches, so they come in useful to establish
      comparisons with similar methods. Furthermore, biological meaning is extracted
      from the leukemia results, and compared with previous studies. In summary, the
      approaches presented here give rise to sparse, interpretable models that are
      competitive with similar methods developed in the field.

PMID- 20812910
TI  - Mapping quantitative trait loci in a non-equilibrium population.
AB  - The genetic control of a complex trait can be studied by testing and mapping the
      genotypes of the underlying quantitative trait loci (QTLs) through their
      associations with observable marker genotypes. All existing statistical methods
      for QTL mapping assume an equilibrium population, allowing marker-QTL
      associations to be simply described at the gametic level. However, many mapping
      populations in practice may deviate from equilibrium; thus, gametic associations
      cannot reflect marker-QTL associations at the genotype level. We develop a robust
      model for mapping QTLs in a non-equilibrium natural population in which
      individuals are not necessarily randomly mating due to various evolutionary
      forces. Without use of Hardy-Weinberg equilibrium, the new model founds marker
      QTL associations directly on the genotypes, specified by a group of
      disequilibrium parameters. Simulation studies were performed to test the
      statistical properties of the model, which suggests that the new model covers
      current mapping models and can be safely used for any data set.

PMID- 20812911
TI  - On the optimal design of genetic variant discovery studies.
AB  - The recent emergence of massively parallel sequencing technologies has enabled an
      increasing number of human genome re-sequencing studies, notable among them being
      the 1000 Genomes Project. The main aim of these studies is to identify the yet
      unknown genetic variants in a genomic region, mostly low frequency variants
      (frequency less than 5%). We propose here a set of statistical tools that address
      how to optimally design such studies in order to increase the number of genetic
      variants we expect to discover. Within this framework, the tradeoff between lower
      coverage for more individuals and higher coverage for fewer individuals can be
      naturally solved. The methods here are also useful for estimating the number of
      genetic variants missed in a discovery study performed at low coverage. We show
      applications to simulated data based on coalescent models and to sequence data
      from the ENCODE project. In particular, we show the extent to which combining
      data from multiple populations in a discovery study may increase the number of
      genetic variants identified relative to studies on single populations.

PMID- 20812912
TI  - Pedagogy as influencing nursing students' essentialized understanding of culture.
AB  - In this qualitative study, we explored how students understood "culture."
      Participants defined culture and wrote narratives regarding specific cultural
      encounters. The sample comprised both nursing (n=14) and non-nursing (n=8)
      students to allow for comparison groups. Content analysis of the narratives
      revealed two broad paradigms of cultural understanding: essentialist and
      constructivist. Essentialist narratives comprised four themes: determinism
      (culture defied individual resistance); relativism (the possibility of making
      value judgments disappeared); Othering (culture was equated to exotica, and
      emphasized difference); and, reductionism (personhood was eclipsed by culture).
      In contrast, the constructivist narratives were characterized by influence (non
      determinism), dynamism (culture was dynamic and evolutionary); and, relationship
      building. The unintended negative consequences of essentialist notions of culture
      were revealed in the nursing students' narratives. Pedagogy is implicated in
      nursing students' essentialized understanding of culture.

PMID- 20812913
TI  - Beyond google: finding and evaluating web-based information for community-based
      nursing practice.
AB  - Nurses are challenged to find and use reliable, credible information to support
      clinical decision-making and to meet expectations for evidence-based nursing
      practice. This project targeted practicing public health and school nurses,
      teaching them how to access and critically evaluate web-based information
      resources for frontline practice. Health sciences librarians partnered with
      nursing faculty to develop two participatory workshops to teach skills in
      searching for and evaluating web-based consumer and professional practice
      resources. The first workshop reviewed reliable, credible consumer web-resources
      appropriate to use with clients, using published criteria to evaluate website
      credibility. In the second workshop, nurses were taught how to retrieve and
      evaluate health-related research from professional databases to support evidence
      based nursing practice. Evaluation data indicated nurses most valued knowing
      about the array of reliable, credible web-based health information resources,
      learning how to evaluate website credibility, and understanding how to find and
      apply professional research literature to their own practice.

PMID- 20812914
TI  - Similarities and differences in the structure and function of 4.1G and 4.1R135,
      two protein 4.1 paralogues expressed in erythroid cells.
AB  - Membrane skeletal protein 4.1R is the prototypical member of a family of four
      highly paralogous proteins that include 4.1G, 4.1N and 4.1B. Two isoforms of 4.1R
      (4.1R135 and 4.1R80), as well as 4.1G, are expressed in erythroblasts during
      terminal differentiation, but only 4.1R80 is present in mature erythrocytes.
      Although the function of 4.1R isoforms in erythroid cells has been well
      characterized, there is little or no information on the function of 4.1G in these
      cells. In the present study, we performed detailed characterization of the
      interaction of 4.1G with various erythroid membrane proteins and the regulation
      of these interactions by calcium-saturated calmodulin. Like both isoforms of
      4.1R, 4.1G bound to band 3, glycophorin C, CD44, p55 and calmodulin. While both
      4.1G and 4.1R135 interact with similar affinity with CD44 and p55, there are
      significant differences in the affinity of their interaction with band 3 and
      glycophorin C. This difference in affinity is related to the non-conserved N
      terminal headpiece region of the two proteins that is upstream of the 30 kDa
      membrane-binding domain that harbours the binding sites for the various membrane
      proteins. The headpiece region of 4.1G also contains a high-affinity calcium
      dependent calmodulin-binding site that plays a key role in modulating its
      interaction with various membrane proteins. We suggest that expression of the two
      paralogues of protein 4.1 with different affinities for band 3 and glycophorin C
      is likely to play a role in assembly of these two membrane proteins during
      terminal erythroid differentiation.

PMID- 20812915
TI  - PMS-1077, a PAF antagonist, induced differentiation of HL-60 cells with its novel
      activity.
AB  - The cell differentiation-inducing effect of 2-N,N-diethylaminocarbonyloxymethyl-1
      diphenylmethyl-4-(3,4,5-trimethoxybenzoyl) piperazine, hydrochloride (PMS-1077)
      was determined in human leukaemic HL-60 cells with profiling of cell
      proliferation, analysis of cell cycling, characterization of expression of
      various CD molecules and determination of phagocytotic activity of differentiated
      HL-60 cells. After treatment with PMS-1077, HL-60 cells exhibited a decreased
      cell viability during which cell cycle was arrested in G0-/G1-phase. Flow
      cytometric analysis showed CD11b and CD14 were up-regulated, whereas CD15 was
      unaffected. Together with the finding that PMS-1077-treated HL-60 cells exhibited
      activities of differentiation by examining their ability of phagocytosing latex
      beads, an antiproliferative effect and a differentiation-inducing role were
      determined for PMS-1077 in HL-60 cells.

PMID- 20812918
TI  - Image cytometric measurements of diploid, triploid and tetraploid fish
      erythrocytes in blood smears reflect the true dimensions of live cells.
AB  - Comparative image cytometry of erythrocytes of diploid and triploid tench Tinca
      tinca L. and evolutionary tetraploid sterlet Acipenser ruthenus L. was performed
      on whole live unstained cells, live cells with stained nuclei and on stained
      fixed whole cells and their nuclei to test if erythrocyte measurements made from
      blood smears reflect the true dimensions of live cells. Nuclear area and
      perimeter were the best ploidy level predictors distinguishing accurately among
      live and fixed diploid, triploid and tetraploid cells, without significant
      differences between live and fixed cells within a ploidy level. Redundancy
      analysis revealed insignificant marginal effect of fixation (explained 2.3% of
      variation, F = 0.804), whereas the effect of ploidy level was highly significant
      (explained 50.6% of variation, F = 34.874). The erythrocyte measurements of
      diploid, triploid and tetraploid fish erythrocytes and their nuclei made from
      blood smears reflect the true dimensions of live cells, and the fixation
      procedure did not substantially affect their predictive value for ploidy level
      determination.

PMID- 20812917
TI  - Chondroitin sulfate N-acetylgalactosaminyltransferase-1 is required for normal
      cartilage development.
AB  - CS (chondroitin sulfate) is a glycosaminoglycan species that is widely
      distributed in the extracellular matrix. To understand the physiological roles of
      enzymes involved in CS synthesis, we produced CSGalNAcT1 (CS N
      acetylgalactosaminyltransferase 1)-null mice. CS production was reduced by
      approximately half in CSGalNAcT1-null mice, and the amount of short-chain CS was
      also reduced. Moreover, the cartilage of the null mice was significantly smaller
      than that of wild-type mice. Additionally, type-II collagen fibres in developing
      cartilage were abnormally aggregated and disarranged in the homozygous mutant
      mice. These results suggest that CSGalNAcT1 is required for normal CS production
      in developing cartilage.

PMID- 20812919
TI  - Induction of apoptosis and lipogenesis in human preadipocyte cell line by n-3
      PUFAs.
AB  - We examined the effect of n-3 PUFAs (polyunsaturated fatty acids) on the growth
      and maturation of human preadipocyte cell line AML-I. On day 3 of the culture, n
      3 fatty acids such as DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid),
      but not n-6 fatty acid LA (linoleic acid), induced growth arrest accompanied by
      the appearance of characteristics of apoptosis in AML-I cells at concentrations
      between 250 and 500 MUM by Annexin V-FITC staining. In Western blotting analysis,
      the loss of NF-kappaB, Bcl-2 and p-Akt and the accumulation of Bad and Akt were
      observed in the cytoplasmic protein from the EPA-treated cells. Exposure of AML-I
      to EPA or DHA increased the cytoplasmic lipid accumulation compared with the
      vehicle-treated cells in a time-dependent manner during 4 and 6 days culture
      period by Oil Red O staining. The expression of FAS (fatty acid synthase) and
      PPAR-gamma (peroxisome proliferator-activated receptor-gamma) were increased in
      EPA-treated cells. These results suggest that EPA and DHA promote
      differentiation, inhibit proliferation and induce apoptosis in preadipocyte cell
      line AML-I.

PMID- 20812916
TI  - Reverse genetics in eukaryotes.
AB  - Reverse genetics consists in the modification of the activity of a target gene to
      analyse the phenotypic consequences. Four main approaches are used towards this
      goal and will be explained in this review. Two of them are centred on genome
      alterations. Mutations produced by random chemical or insertional mutagenesis can
      be screened to recover only mutants in a specific gene of interest.
      Alternatively, these alterations may be specifically targeted on a gene of
      interest by HR (homologous recombination). The other two approaches are centred
      on mRNA. RNA interference is a powerful method to reduce the level of gene
      products, while MO (morpholino) antisense oligonucleotides alter mRNA metabolism
      or translation. Some model species, such as Drosophila, are amenable to most of
      these approaches, whereas other model species are restricted to one of them. For
      example, in mice and yeasts, gene targeting by HR is prevalent, whereas in
      Xenopus and zebrafish MO oligonucleotides are mainly used. Genome-wide
      collections of mutants or inactivated models obtained in several species by these
      approaches have been made and will help decipher gene functions in the post
      genomic era.

PMID- 20812920
TI  - The novel nomogram of Gleason sum upgrade: possible application for the eligible
      criteria of low dose rate brachytherapy.
AB  - OBJECTIVE: To examine the rate of Gleason sum upgrading (GSU) from a sum of 6 to
      a Gleason sum of >=7 in patients undergoing radical prostatectomy (RP), who
      fulfilled the recommendations for low dose rate brachytherapy (Gleason sum 6,
      prostate-specific antigen <=10 ng/mL, clinical stage <=T2a and prostate volume
      <=50 mL), and to test the performance of an existing nomogram for prediction of
      GSU in this specific cohort of patients. METHODS: The analysis focused on 414
      patients, who fulfilled the European Society for Therapeutic Radiation and
      Oncology and American Brachytherapy Society criteria for low dose rate
      brachytherapy (LD-BT) and underwent a 10-core prostate biopsy followed by RP. The
      rate of GSU was tabulated and the ability of available clinical and pathological
      parameters for predicting GSU was tested. Finally, the performance of an existing
      GSU nomogram was explored. RESULTS: The overall rate of GSU was 35.5%. When
      applied to LD-BT candidates, the existing nomogram was 65.8% accurate versus
      70.8% for the new nomogram. In decision curve analysis tests, the new nomogram
      fared substantially better than the assumption that no patient is upgraded and
      better than the existing nomogram. CONCLUSIONS: GSU represents an important issue
      in LD-BT candidates. The new nomogram might improve patient selection for LD-BT
      and cancer control outcome by excluding patients with an elevated probability of
      GSU.

PMID- 20812921
TI  - Combined treatment involving unilateral common iliac embolization and femoro
      femoral arterial bypass for lower gastrointestinal bleeding due to recurrent
      bladder cancer.

PMID- 20812922
TI  - Template-based lymphadenectomy in urothelial carcinoma of the upper urinary
      tract: impact on patient survival.
AB  - OBJECTIVES: The benefit of lymphadenectomy (LND) in patients with urothelial
      carcinoma of the upper urinary tract (UCUUT) has remained controversial. The aim
      of this study was to examine the influence of the LND template and the total
      number of lymph nodes (LN) when increasing the number of patients undergoing
      complete dissection of regional nodes (CompLND). METHODS: A total of 109 UCUUT
      patients with clinically negative nodes underwent nephroureterectomy with
      concomitant lymphadenectomy at our center. Patients' survival was examined
      according to the type of LND and the number of removed LN. Univariate analysis
      was performed to find the cut-off value of LN influencing survival. RESULTS:
      Seventy-eight patients underwent CompLND. Incomplete lymphadenectomy was
      performed in an additional 41 patients. In the patients with pT2 or higher who
      were clinically negative for nodal metastasis, any cut-off value for the total
      number of LN removed showed no statistical significance. In contrast, CompLND had
      a significant impact on patient survival. The Cox proportional hazard model
      showed that CompLND was a significant factor after adjusting for adjuvant
      chemotherapy. The total number of removed LN was not significant. CONCLUSIONS: In
      patients with muscle-invasive clinical node-negative UCUUT, the number of LN
      removed shows minimal influence on their survival. In contrast, the influence of
      the particular type of lymphadenectomy is statistically significant. These
      findings suggest that the extent of lymphadenectomy should be determined by the
      template and not by the number of removed LN.

PMID- 20812923
TI  - Idiopathic ventricular fibrillation controlled successfully with phenytoin.
AB  - We describe a case of an individual with idiopathic ventricular fibrillation
      whose arrhythmias were successfully controlled with phenytoin therapy.

PMID- 20812924
TI  - AF News.

PMID- 20812925
TI  - Remission of abnormal conduction and repolarization in the right ventricle after
      chemotherapy in patients with anterior mediastinal tumor.

PMID- 20812926
TI  - The challenge of preventing stroke in elderly patients with atrial fibrillation.

PMID- 20812927
TI  - An alternate form of endless loop arrhythmia: what are the mechanism and
      potential solutions?

PMID- 20812928
TI  - Eccentric activation of coronary sinus during perimitral flutter is a rare
      phenomenon: what is the mechanism?

PMID- 20812929
TI  - Effect of therapeutic INR on activated clotting times, heparin dosage, and
      bleeding risk during ablation of atrial fibrillation.
AB  - BACKGROUND: Ablation of atrial fibrillation (AF) with international normalized
      ratio (INR) >= 2.0 is safe and may reduce thromboembolic complications. Heparin
      is administered during the procedure, but the effect of elevated INR on heparin
      requirements and target activation clotting times (ACT) >= 350 seconds during
      ablation is unknown. OBJECTIVES: To study the effect of INR on intraprocedural
      anticoagulation during ablation of AF. METHODS: We retrospectively studied 427
      consecutive patients over an 18-month period when we were transitioning to
      continuation of warfarin for AF ablation. Baseline INR, procedural ACT
      measurements, heparin doses and major complications were analyzed according to
      Group 1 with INR < 2.0 (n = 246) and Group 2 with INR >= 2.0 (n = 181). RESULTS:
      In Group 1, the mean INR was lower (1.3 +/- 0.3 s vs 2.4 +/- 0.3; P < 0.001), and
      the mean heparin dose was greater (106.82 +/- 40.01 vs 77.03 +/- 18.5 U/kg; P <
      0.001). A single heparin bolus achieved ACT >= 350 seconds throughout the
      procedure in 51 patients (20.7%) in Group 1 compared to 108 patients (59.7%) in
      Group 2 (P < 0.01). Mean ACT values were higher in Group 2. Symptomatic
      pericardial effusions were similar (2.4% in Group 1 and 2.2% in Group 2). There
      were 3 thromboembolic cerebrovascular events in Group 1 and none in Group 2.
      Femoral hematomas occurred more frequently in Group 1 (8.1%) than in Group 2
      (3.3%) (P = 0.007). CONCLUSIONS: AF ablation with INR >= 2.0 provides a
      consistent anticoagulant milieu during the procedure, with lower heparin
      requirements that are important to anticipate.

PMID- 20812930
TI  - Paradoxical effects of interatrial conduction delay in a hypertrophic
      cardiomyopathy patient in the long-term: time is a great healer.
AB  - We present a unique case where early proarrhythmic and late antiarrhythmic
      characteristics of interatrial conduction delay were observed during the long
      term progression of HCM. Occurrence of AT constantly increased as the interatrial
      conduction delay became more prominent, while the P-wave width in sinus rhythm
      and the AT cycle length both showed an instantaneous increase in parallel. As the
      interatrial delay reached a critical point, the right and left atrial P-wave
      became virtually separated, as demonstrated by the findings of ECGs and
      echocardiography. This phenomenon resulted in the complete cessation of
      tachycardias.

PMID- 20812931
TI  - Sodium channelopathies: do we really understand what's going on?
AB  - Long-QT syndrome, Brugada syndrome, and conduction disease may be caused by
      mutations in the cardiac sodium channel gene SCN5A, and from the ECG one can
      already presume either a gain- or a loss-of-function defect. We describe a family
      harboring 2 SCN5A mutations: the DeltaKPQ mutation, the "classical" gain-of
      function mutation associated with Long-QT syndrome, and the I1660V mutation, a
      loss-of-function mutation associated with Brugada syndrome. However, we were
      surprised by the result of genetic testing in this family. One son who carried
      the DeltaKPQ mutation but not the I1660V mutation did not show the expected Long
      QT phenotype but, unexpectedly, showed a conduction disease/Brugada phenotype.

PMID- 20812932
TI  - Brugada syndrome, haissaguerre syndrome, or ischemic j-waves: are we looking at
      different angles of the same triangle?

PMID- 20812933
TI  - Remifentanil-midazolam sedation provides hemodynamic stability and comfort during
      epicardial ablation of ventricular tachycardia.
AB  - Epicardial ablation of ventricular tachycardia (VT) presents multiple challenges
      for anesthetic management. General anesthesia lowers blood pressure, may
      interfere with arrhythmia mapping, and use of muscle relaxants precludes
      identification of the phrenic nerve. We describe a case in which remifentanil
      with minimal doses of midazolam was employed in a series of epicardial VT
      ablations and noninvasive programmed stimulations (NIPS), including 5 external
      cardioversions and discuss the advantages of this approach.

PMID- 20812934
TI  - Catheter ablation of ventricular tachycardias due to forward and reverse
      propagation across a reentrant circuit inside a nonischemic biventricular
      aneurysm.
AB  - A 64-year-old recipient of implantable cardioverter defibrillator presenting with
      a 4.7 * 3.3 cm nonischemic, biventricular aneurysm developed multiple electrical
      storms due to ventricular tachycardia (VT) with 2 distinct QRS morphologies.
      Endocardial electroanatomical mapping revealed the presence of a low-voltage area
      corresponding to the aneurysm, where multiple delayed potentials were recorded.
      Activation mapping and entrainment pacing of both VT revealed the, respectively,
      forward and reverse propagation of the wavefront across a single reentrant
      circuit inside the ventricular aneurysm. Delivery of 3 applications of
      radiofrequency energy to a critical segment of the reentrant pathway eliminated
      both VT and the electrical storms.

PMID- 20812935
TI  - The atria: from morphology to function.
AB  - The fact that some atrial and ventricular disorders (e.g., atrial fibrillation
      and heart failure) have a structural basis and cause atrial myocardial remodeling
      has led to increasing attention being paid to the atrial chambers. Furthermore,
      the rapid development of mapping and ablative procedures as a means of diagnosing
      and treating supraventricular arrhythmias has generated considerable interest in
      atrial gross anatomy, histology and ultrastructure. The aim of this article is to
      provide a comprehensive overview of the structure of the left and right atria (at
      macroscopic, histological and ultrastructural level) in relation to their
      function. In addition to analyzing normal atria, we also discuss functional
      anatomy in the case of atrial fibrillation and heart failure.

PMID- 20812936
TI  - Pulmonary vein isolation alone in patients with persistent atrial fibrillation:
      an ablation strategy facilitated by antiarrhythmic drug induced reverse
      remodeling.
AB  - INTRODUCTION: Pulmonary vein isolation (PVI) alone has been thought to be
      insufficient in patients with persistent atrial fibrillation (PersAF). We
      hypothesized that preablation treatment of PersAF with a potent antiarrhythmic
      drug (AAD) would facilitate reverse atrial remodeling and result in high
      procedural efficacy after PVI alone. METHODS AND RESULTS: Seventy-one consecutive
      patients (59.4 +/- 9.8 years) with PersAF and prior AAD failure were treated with
      oral dofetilide (768 +/- 291 mcg/day) for a median of 85 days pre-PVI. P-wave
      duration (Pdur) on ECG was used to assess reverse atrial remodeling. Thirty-five
      patients with paroxysmal (P) AF not treated with an AAD served as controls. All
      patients underwent PVI alone; dofetilide was discontinued 1-3 mos postablation.
      In the PersAF patients, the Pdur decreased from 136.3 +/- 21.7 ms (assessed
      postcardioversion on dofetilide) to 118.6 +/- 20.4 ms (assessed immediately prior
      to PVI) (P < 0.001). In contrast, no change in Pdur (122.6 +/- 11.5 ms vs. 121.3
      +/- 13.7 ms, P = NS) was observed in PAF patients. The 6 and 12 mos AAD-free
      response to ablation was 76% and 70%, respectively, in PersAF patients, similar
      to the 80% and 75%, response in PAF patients (P = NS). A decline in Pdur in
      response to dofetilide was the only predictor of long-term clinical response to
      PVI in patients with PersAF. CONCLUSIONS: Pre-treatment with AAD resulted in a
      decrease in Pdur suggesting reverse atrial electrical remodeling in PersAF
      patients. This may explain the excellent clinical outcomes using PVI alone, and
      may suggest an alternative ablation strategy for PersAF.

PMID- 20812937
TI  - Pulmonary vein antral isolation for paroxysmal atrial fibrillation: results from
      long-term follow-up.
AB  - INTRODUCTION: Pulmonary veins play an important role in triggering atrial
      fibrillation (AF). Pulmonary vein isolation (PVI) is an effective treatment for
      patients with paroxysmal AF. However, the late AF recurrence rate in long-term
      follow-up of circumferential PV antral isolation (PVAI) is not well documented.
      We sought to determine the time to recurrence of arrhythmia after PVAI, and long
      term rates of sinus rhythm after circumferential PVAI. METHODS: One hundred
      consecutive patients with a mean age of 54 +/- 10 years, with paroxysmal AF who
      underwent PVAI procedure were analyzed. Isolation of pulmonary veins was based on
      an electrophysiological and anatomical approach, with a nonfluoroscopic
      navigation mapping system to guide antral PVI. Ablation endpoint was vein
      isolation confirmed with a circular mapping catheter at first and subsequent
      procedures. Clinical, ECG, and Holter follow-up was undertaken every 3 months in
      the first year postablation, every 6 months thereafter, with additional prolonged
      monitoring if symptoms were reported. Time to arrhythmia recurrence, and
      representing arrhythmias, were documented. RESULTS: Isolation of all 4 veins was
      successful in 97% patients with 3.9 +/- 0.3 veins isolated/patient. Follow-up
      after the last RF procedure was at a mean of 39 +/- 10 months (range 21-66
      months). After a single procedure, sinus rhythm was maintained at long-term
      follow-up in 49% patients without use of antiarrhythmic drugs (AADs). After
      repeat procedure, sinus rhythm was maintained in 57% patients without the use of
      AADs, and in 82% patients including patients with AADs. A total of 18 of 100
      patients had 2 procedures and 4 of 100 patients had 3 procedures for recurrent
      AF/AT. Most (86%) AF/AT recurrences occurred <= 1 year after the first procedure.
      Mean time to recurrence was 6 +/- 10 months. Kaplan-Meier analysis on
      antiarrhythmics showed AF free rate of 87% at 1 year and 80% at 4 years. There
      were no major complications. CONCLUSION: PVAI is an effective strategy for the
      prevention of AF in the majority of patients with PAF. Maintenance of SR requires
      repeat procedure or continuation of AADs in a significant proportion of patients.
      After maintenance of sinus rhythm 1-year post-PVAI, a minority of patients will
      subsequently develop late recurrence of AF.

PMID- 20812938
TI  - Technique for a hybrid system of real-time transrectal ultrasound with
      preoperative magnetic resonance imaging in the guidance of targeted prostate
      biopsy.
AB  - Diagnostic magnetic resonance imaging (MRI) for prostate has achieved
      increasingly higher levels of accuracy. Because real-time MR-guided targeted
      biopsy is still a complicated and expensive procedure, there is considerable
      interest in a technique of MR/transrectal ultrasound (TRUS) hybridized image
      guided biopsy. However, because the 3-D shapes of the prostate at the time of
      image-acquisition at preoperative MRI are likely to be different from the intra
      operative TRUS images, the precise registration of each 3-D volume data is
      critical. To reduce the potential errors in registration of TRUS with MRI, we
      introduce new procedural techniques in a rigid image fusion technique. First,
      preoperative MR images were obtained with a specifically-made plastic outer
      frame, with exactly the same shape as the real TRUS probe, placed in the rectum,
      in order to simulate the deformation of the prostate caused by the absence or
      presence of a TRUS probe during the acquisition of MR or TRUS images. Second,
      instead of using a single plane of longitudinal image, we applied biplane TRUS
      images to be shown in parallel on a multiplanar display with corresponding
      reconstructed MRI, in order to register both horizontal and longitudinal images
      of the prostate simultaneously, thereby achieving improved 3-D anatomical
      matching.

PMID- 20812939
TI  - Twenty-nine Leydig cell tumors: histological features, outcomes and implications
      for management.
AB  - Leydig cell tumors are the most common interstitial neoplasm of the testes.
      Metastatic progression is historically quoted at over 10%, fuelling uncertainty
      as to the safety of testis sparing surgery. Between June 1998 and March 2009, 29
      patients underwent surgery for Leydig cell tumor of the testis in our cancer
      network. We reviewed their histological features and clinical outcomes. Four
      patients with sub-5 millimetre lesions underwent testis sparing surgery and 25
      were treated with radical orchidectomy. Histopathological characteristics that
      have been linked with risk of malignant progression were seen infrequently in our
      cohort: diameter greater than 50 mm, 0%; nuclear atypia, 14%; >3 mitoses per 10
      high-power fields, 3%; infiltrative borders, 10%; necrosis, 3%; and vascular
      invasion 0%. No patient developed local or distant recurrent disease over a
      median follow up of 49 months, including seven and four patients disease-free at
      5 and 10 years, respectively. The rate of metastatic progression is likely to be
      significantly less than 10%. Our data suggest that, in the absence of high-risk
      histopathological features, this tumor can be safely regarded as benign, pending
      a longer-term follow-up evaluation.

PMID- 20812940
TI  - Impact of high-consistency area evaluated under hand-operated transrectal
      compression using a sonographic probe on prostate cancer detection:
      clinicopathological analysis.
AB  - Aim of this investigation was to determine whether the evaluation of a new
      dynamic finding on conventional greyscale transrectal ultrasonography (TRUS),
      which we named as high-consistency area (HCA), is useful in detection of prostate
      cancer (PCa). Fifty-one consecutive patients were prospectively enrolled in this
      study. When TRUS-guided prostate biopsy was performed, HCA that was difficult to
      transform, due to transrectal compression using sonographic probe, was evaluated.
      HCA-targeting biopsy, digital rectal examination (DRE)-targeting biopsy and
      systematic 12-core biopsy were performed. All biopsy cores were diagnosed
      histopathologically. As the results, twenty-three PCas were detected in 51
      patients. The sensitivity and specificity of HCA-targeting biopsy for correct
      diagnosis were 60.9% and 78.6%, respectively. The sensitivity and specificity for
      DRE-targeting biopsy were 47.8% and 78.6%, respectively. In conclusion, HCA
      targeting biopsy of this study was superior to DRE-targeting biopsy with regard
      to detection of PCa. Before prostate biopsy, patients should be evaluated for DRE
      and HCA, and DRE and HCA-targeting biopsy should be performed.

PMID- 20812941
TI  - A laboratory evaluation of the antibacterial and cytotoxic effect of Liquorice
      when used as root canal medicament.
AB  - AIM: To evaluate the antibacterial and cytotoxic effects of Liquorice as a root
      canal medicament and to compare its action to the commonly used root canal
      medicament calcium hydroxide Ca(OH)(2). METHODOLOGY: The antibacterial effect of
      Liquorice and Ca(OH)(2) either separately or in combination was investigated
      against Enterococcus faecalis. Agar-well diffusion methods, broth microdilution
      tests and biofilm susceptibility assays were used to determine the antibacterial
      activity. Human periodontal ligament fibroblast tissue culture was used to assess
      the cytotoxicity of the preparations under investigation. RESULTS: Liquorice
      extract either by itself or in combination with Ca(OH)(2) had a significant
      inhibitory effect against Enterococcus faecalis compared with that of Ca(OH)(2)
      alone. The use of Liquorice extract followed by Liquorice/Ca(OH)(2) mixture
      retained significantly more viable periodontal ligament cells than Ca(OH)(2) ,
      which had a strong lethal effect on the cells. CONCLUSION: Liquorice extract
      either separately or as Liquorice/Ca(OH)(2) mixture had a potent bactericidal
      effect against Enterococcus faecalis and retained compatibility with fibroblasts
      in tissue culture compared to the commonly used root canal medicament Ca(OH)(2).

PMID- 20812942
TI  - Effect of tricalcium aluminate on the properties of tricalcium silicate
      tricalcium aluminate mixtures: setting time, mechanical strength and
      biocompatibility.
AB  - AIM: To prepare biphasic mixtures by adding Ca(3) Al(2) O(6) into Ca(3) SiO(5)
      and to evaluate the effect of Ca(3) Al(2) O(6) on physical and ex vivo biological
      properties of the Ca(3) SiO(5) /Ca(3) Al(2) O(6) mixtures derived from mineral
      trioxide aggregate (MTA). METHODOLOGY: Combinations of Ca(3) SiO(5) and Ca(3)
      Al(2) O(6) (0, 5%, 10% and 15%) powders were mixed with deionized water. After
      hydration, setting time, compressive strength, ex vivo bioactivity and
      biocompatibility of each mixture were investigated and compared to pure Ca(3)
      SiO(5) . RESULTS: With the addition of Ca(3) Al(2) O(6) from 0% to 15%, the
      initial setting time and final setting time of the Ca(3) SiO(5) /Ca(3) Al(2) O(6)
      mixtures decreased from 110 to 43min and from 220 to 97min, respectively
      (P<=0.05). However, the compressive strength increased from 6.75 to 16.20MPa
      after one day (P<=0.05) and from 17.73 to 29.13 Mpa after 28 days. Furthermore,
      the mixtures with 10% Ca(3) Al(2) O(6) or less had similar bioactivity and
      biocompatibility when compared to the pure Ca(3) SiO(5). CONCLUSIONS: The
      addition of Ca(3) Al(2) O(6) into Ca(3) SiO(5) accelerated the hydration process,
      reduced the setting time and improved the compressive strength. Furthermore,
      these mixtures were bioactive and biocompatible and had a stimulatory effect on
      the L929 cell growth when the content of Ca(3) Al(2) O(6) was below 10%.
      Therefore, the mixtures with 10% Ca(3) Al(2) O(6) produced the best compromise
      between hydration and ex vivo biological properties.

PMID- 20812943
TI  - The response of dental pulp-derived cells to zoledronate depends on the
      experimental model.
AB  - AIM: To investigate whether zoledronate (ZOL) can cause a cytotoxic response in
      dental pulp-derived cells (DPCs) in vitro. METHODOLOGY: Cell activity was
      assessed utilizing MTT tests, (3) [H]thymidine, and (3) [H]leucine incorporation
      assays in human DPCs in response to ZOL. Cell activity assays were also preformed
      on calcium phosphate-coated plates. Cell death was analysed with annexin
      V/propidium iodide, trypan blue staining and Western blot analysis. RESULTS:
      Micromolar concentrations of ZOL were required to decrease the activity of DPCs.
      The decreased activity of DPCs was associated with the occurrence of apoptosis
      and necrosis. No adverse effects were observed when DPCs were cultured on calcium
      phosphate-coated plates with ZOL. CONCLUSION: High concentrations of soluble ZOL
      were required to cause adverse effects in vitro. These adverse effects are
      abolished when the bisphosphonate was bound to a mineralized surface. However,
      the clinical relevance of these results remains to be determined.

PMID- 20812944
TI  - Why do general dental practitioners refer to a specific specialist endodontist in
      practice?
AB  - AIMS: To identify the factors that influence the decision of general dental
      practitioners (GDPs) in Northern Ireland to refer to a specific specialist
      endodontist. METHODOLOGY: A self-administered questionnaire was sent to 220 GDPs
      in Northern Ireland. The questionnaire comprised questions on demographic
      characteristics, pattern of practice, pattern of referral and factors influencing
      the decision to refer to a specific specialist endodontist in practice. The data
      were analysed using descriptive statistics and the chi-squared (chi(2) ) test at
      the 0.05 level of significance. RESULTS: The response rate was 81%. All
      respondents stated that they carried out root canal treatment, and the majority
      (83%) stated that they also carried out root canal retreatment. A minority of
      respondents (11%) stated that they carried out surgical endodontics. These
      individuals were more likely to be men, hold a postgraduate qualification, or
      work in a rural location. The majority of respondents (94%) referred patients
      with an endodontic problem. These individuals were more likely to be women, not
      hold a postgraduate qualification, or not carry out surgical endodontics. GDPs
      indicated a preference for referring to a specialist endodontist in practice over
      other treatment providers. Factors considered to be of importance in the decision
      to refer to a specialist endodontist in practice included the practice location
      of, reputation of, communication with and patient management by the specialist
      endodontist. The greatest proportion of respondents ranked short waiting time for
      a consultation as the top promoter when referring to a specific specialist
      endodontist in practice. CONCLUSION: The decision by GDPs to refer to a specific
      specialist endodontist in practice is multifactorial and influenced by several
      factors independent from the nature of endodontic disease. In Northern Ireland,
      the top promoter for referring to a specific specialist endodontist in practice
      was a relatively short waiting time for a consultation.

PMID- 20812945
TI  - The anatomy of the root canal system of three-rooted maxillary premolars analysed
      using high-resolution computed tomography.
AB  - AIM: To analyse the anatomy of the root canal system of maxillary premolars with
      three distinct roots using high-resolution computed tomography (MUCT).
      METHODOLOGY: Ten three-rooted human maxillary premolars were scanned
      transversally from crown to apex at 42MUm intervals using a high-resolution
      desktop MUTC system (Skyscan 1072). The images were processed and analysed for
      the following features: cross section of the roots and canals in the apical,
      middle and coronal thirds; location of the apical foramen; distance from the pulp
      chamber roof to the bifurcation and trifurcation of the canals and anatomic
      variations of the root canal system. The results were expressed descriptively.
      RESULTS: The cross-sectional shape of canals was heterogeneous along the length
      of the roots. The location of the apical foramen varied, tending to lie palatally
      or distally. The buccal pulp horn was larger than the palatal. The mean distance
      from the most cervical region of the pulp chamber roof to the bifurcation and
      trifurcation of the canals was 3.13 and 5.08mm, respectively. CONCLUSIONS:
      Features of the internal anatomy of the pulp cavity of three-rooted maxillary
      premolars were identified with the use of MUCT. The results revealed the
      heterogeneity of three-rooted maxillary premolars.

PMID- 20812946
TI  - Effect of bioaggregate on differentiation of human periodontal ligament
      fibroblasts.
AB  - AIM: To investigate the cytotoxicity of bioaggregate (BA; Innovative Bioceramix,
      Vancouver, BC, Canada) to human periodontal ligament (PDL) fibroblasts and its
      effect on differentiation of human PDL fibroblasts and to compare its performance
      to that of mineral trioxide aggregate (MTA; Dentsply, Tulsa, OK, USA).
      METHODOLOGY: Cytotoxicity was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay on days 1, 2, and 3 after incubation with
      BA or MTA. The influence of BA and MTA on differentiation of human PDL
      fibroblasts on days 3, 5, and 7 was evaluated by gene expression of alkaline
      phosphatase (ALP) and collagen type I (COLI) via quantitative real-time
      polymerase chain reaction (PCR). The data were analysed by one-way analysis of
      variance followed by Tukey's test. RESULTS: Cell numbers in the BA group were
      similar to that of the control group throughout the culture period, whereas MTA
      suppressed the proliferation of fibroblasts. ALP expression was significantly
      increased in the BA group on day 7, whilst it was enhanced by MTA on day 3. Gene
      expression of COLI was induced by both BA and MTA compared to the control group.
      CONCLUSIONS: Bioaggregate was nontoxic to human PDL fibroblasts and appeared to
      induce the differentiation of human PDL fibroblasts.

PMID- 20812947
TI  - Reaction rate of NaOCl in contact with bovine dentine: effect of activation,
      exposure time, concentration and pH.
AB  - AIM: To determine the influence of activation method (ultrasound or laser),
      concentration, pH and exposure time on the reaction rate (RR) of NaOCl when in
      contact with dentinal walls. METHODOLOGY: The walls from standardized root canals
      in bovine incisors were exposed to a standardized volume of sodium hypochlorite
      (NaOCl) with different concentrations (2% and 10%), pH (5 and 12) and exposure
      times (1 and 4min). Two irrigation protocols were tested: passive ultrasonic
      irrigation or laser activated irrigation with no activation as the control. The
      activation interval lasted 1min followed by a rest interval of 3 min with no
      activation. The RR was determined by measuring the iodine concentration using an
      iodine/thiosulfate titration method. RESULTS: Exposure time, concentration and
      activation method influenced the reaction rate of NaOCl whereas pH did not.
      CONCLUSIONS: Activation is a strong modulator of the reaction rate of NaOCl.
      During the rest interval of 3min, the consumption of available chlorine increased
      significantly. This effect seems to be more pronounced after irrigant activation
      by laser. pH did not affect the reaction rate of 2% NaOCl.

PMID- 20812948
TI  - A comparison of the long-term durability of nevirapine, efavirenz and lopinavir
      in routine clinical practice in Europe: a EuroSIDA study.
AB  - OBJECTIVES: The durability of combination antiretroviral therapy (cART) regimens
      can be measured as time to discontinuation because of toxicity or treatment
      failure, development of clinical disease or serious long-term adverse events. The
      aim of this analysis was to compare the durability of nevirapine, efavirenz and
      lopinavir regimens based on these measures. METHODS: Patients starting a
      nevirapine, efavirenz or lopinavir-based cART regimen for the first time after 1
      January 2000 were included in the analysis. Follow-up started >= 3 months after
      initiation of treatment if viral load was <500 HIV-1 RNA copies/mL. Durability
      was measured as discontinuation rate or development/worsening of clinical
      markers. RESULTS: A total of 603 patients (21%) started nevirapine-based cART,
      1465 (51%) efavirenz, and 818 (28%) lopinavir. After adjustment there was no
      significant difference in the risk of discontinuation for any reason between the
      groups on nevirapine and efavirenz (P=0.43) or lopinavir (P=0.13). Compared with
      the nevirapine group, those on efavirenz had a 48% (P=0.0002) and those on
      lopinavir a 63% (P<0.0001) lower risk of discontinuation because of treatment
      failure and a 31% (P=0.01) and 66% (P<.0001) higher risk, respectively, of
      discontinuation because of toxicities or patient/physician choice. There were no
      significant differences in the incidence of non-AIDS-related events, worsening
      anaemia, severe weight loss, increased aspartate aminotransferase (AST)/alanine
      aminotransferase (ALT) levels or increased total cholesterol. Compared with
      patients on nevirapine, those on lopinavir had an 80% higher incidence of high
      density lipoprotein (HDL) cholesterol decreasing below 0.9 mmol/L (P=0.003), but
      there was no significant difference in this variable between those on nevirapine
      and those on efavirenz (P=0.39). CONCLUSIONS: The long-term durability of
      nevirapine-based cART, based on risk of all-cause discontinuation and development
      of long-term adverse events, was comparable to that of efavirenz or lopinavir, in
      patients in routine clinical practice across Europe who initially tolerated and
      virologically responded to their regimen.

PMID- 20812950
TI  - Suppression of Ycf1p function by Cka1p-dependent phosphorylation is attenuated in
      response to salt stress.
AB  - The yeast vacuolar membrane protein Ycf1p and its mammalian counterpart, MRP1,
      belong to the ABCC subfamily of ATP-binding cassette transporters. Genetic
      evidence suggests that the yeast casein kinase 2alpha, Cka1p, negatively
      regulates Ycf1p function via phosphorylation of Ser251 within the N-terminus. In
      this study, we provide strong evidence that Cka1p regulates Ycf1p function via
      phosphorylation of Ser251. We show that the CK2 holoenzyme interacts with Ycf1p.
      However, genetic analysis suggests that only Cka1p is required for Ser251
      phosphorylation, as the deletion of CKA1 significantly reduces Ser251
      phosphorylation in vivo. Furthermore, purified recombinant Cka1p phosphorylates a
      Ycf1p-derived peptide containing Ser251. We also demonstrate that Ycf1p function
      is induced in response to high salt stress. Induction of the Ycf1p function
      strongly correlates with reduced phosphorylation of Ser251. Importantly, Cka1p
      activity in vivo is similarly reduced in response to salt stress, consistent with
      our finding that Cka1p directly phosphorylates Ser251 of Ycf1p. We provide
      genetic and biochemical evidence that strongly suggests that the induction of
      Ycf1p function is the result of decreased phosphorylation of Ser251. In
      conclusion, our work demonstrates a novel biochemical role for Cka1p regulation
      of Ycf1p function in the cellular response of yeast to salt stress.

PMID- 20812952
TI  - Susceptibility of Candida albicans to photodynamic action of 5,10,15,20-tetra(4-N
      methylpyridyl)porphyrin in different media.
AB  - The photodynamic activity of 5,10,15,20-tetra(4-N-methylpyridyl)porphyrin (TMPyP)
      was evaluated in vitro on Candida albicans cells under different experimental
      conditions. This tetracationic porphyrin binds rapidly to C. albicans cells,
      reaching a value of ~1.7 nmol 10(-6) cells when the cellular suspensions (10(6)
      CFU mL(-1) ) were incubated with 5 MUM sensitizer. The amount of cell-bound
      sensitizer is not appreciably changed when cultures are incubating for longer
      times (>15 min) but it diminishes with the number of washing steps.
      Photosensitized inactivation of C. albicans cellular suspensions increases with
      both sensitizer concentration and irradiation time, causing a ~5 log decrease of
      cell survival when the cultures are treated with 5 MUM TMPyP and irradiated for
      30 min. However, the photocytotoxicity decreases after one washing step, with the
      decrease in cell-bound sensitizer. The growth of C. albicans cells was arrested
      when the cultures were exposed to 5 MUM TMPyP and visible light. On agar
      surfaces, the phototoxic effect of this sensitizer, which caused an inactivation
      of C. albicans cells, remained high. No growth was observed in areas containing
      TMPyP and irradiated. Moreover, in small C. albicans colonies, C. albicans cells
      were completely inactivated. These studies indicate that TMPyP is an effective
      sensitizer for photodynamic inactivation of yeasts in both liquid suspensions or
      localized on a surface.

PMID- 20812951
TI  - Heat-killed and gamma-irradiated Brucella strain RB51 stimulates enhanced
      dendritic cell activation, but not function compared with the virulent smooth
      strain 2308.
AB  - Brucella spp. are Gram-negative, facultative intracellular bacterial pathogens
      that cause abortion in livestock and undulant fever in humans worldwide. Brucella
      abortus strain 2308 is a pathogenic strain that affects cattle and humans.
      Currently, there are no efficacious human vaccines available. However, B. abortus
      strain RB51, which is approved by the USDA, is a live-attenuated rough vaccine
      against bovine brucellosis. Live strain RB51 induces protection via CD4(+) and
      CD8(+) T-cell-mediated immunity. To generate an optimal T-cell response, strong
      innate immune responses by dendritic cells (DCs) are crucial. Because of safety
      concerns, the use of live vaccine strain RB51 in humans is limited. Therefore, in
      this study, we analyzed the differential ability of the same doses of live, heat
      killed (HK) and gamma-irradiated (IR) strain RB51 in inducing DC activation and
      function. Smooth strain 2308, live strain RB51 and lipopolysaccharide were used
      as controls. Studies using mouse bone marrow-derived DCs revealed that,
      irrespective of viability, strain RB51 induced greater DC activation than smooth
      strain 2308. Live strain RB51 induced significantly (P<=0.05) higher DC
      maturation than HK and IR strains, and only live strain RB51-infected DCs (at
      multiplicity of infection 1:100) induced significant (P<=0.05) tumor necrosis
      factor-alpha and interleukin-12 secretion.

PMID- 20812953
TI  - Mangrove microniches determine the structural and functional diversity of
      enriched petroleum hydrocarbon-degrading consortia.
AB  - In this study, the combination of culture enrichments and molecular tools was
      used to identify bacterial guilds, plasmids and functional genes potentially
      important in the process of petroleum hydrocarbon (PH) decontamination in
      mangrove microniches (rhizospheres and bulk sediment). In addition, we aimed to
      recover PH-degrading consortia (PHDC) for future use in remediation strategies.
      The PHDC were enriched with petroleum from rhizosphere and bulk sediment samples
      taken from a mangrove chronically polluted with oil hydrocarbons. Southern blot
      hybridization (SBH) assays of PCR amplicons from environmental DNA before
      enrichments resulted in weak positive signals for the functional gene types
      targeted, suggesting that PH-degrading genotypes and plasmids were in low
      abundance in the rhizosphere and bulk sediments. However, after enrichment, these
      genes were detected and strong microniche-dependent differences in the abundance
      and composition of hydrocarbonoclastic bacterial populations, plasmids (IncP
      1alpha, IncP-1beta, IncP-7 and IncP-9) and functional genes (naphthalene,
      extradiol and intradiol dioxygenases) were revealed by in-depth molecular
      analyses [PCR-denaturing gradient gel electrophoresis and hybridization (SBH and
      microarray)]. Our results suggest that, despite the low abundance of PH-degrading
      genes and plasmids in the environmental samples, the original bacterial
      composition of the mangrove microniches determined the structural and functional
      diversity of the PHDC enriched.

PMID- 20812954
TI  - The relationship between liver disease stage and liver fibrosis: a tangled web.
AB  - The structural consequences of chronic liver disease are described as a series of
      liver disease 'stages' with scarring and architectural change that eventually
      destroys and replaces the normal lobular structure of the liver. Fibrosis
      ('excess collagen') and stage have been confused in histological staging systems.
      Fibrosis is part of increasing liver disease stage, but fibrosis and stage are
      different. Staging liver disease is important in routine histopathological
      assessment. Measurement of liver fibrosis is another process. The collagenous
      proportion of a liver biopsy [collagen proportionate area (CPA)] correlates with
      hepatic venous pressure gradient (HVPG), which is of recognized prognostic value.
      CPA at 1 year post-transplantation in hepatitis C virus-infected patients
      predicts subsequent clinical decompensation. CPA in cirrhotic patients predicts
      decompensation more accurately than staging or HVPG. The 'cirrhosis' stage
      category has poor prognostic power, and CPA effectively substages cirrhosis. CPA
      improves the description of liver disease stage. Proper validation of
      antifibrotic treatments and 'non-invasive markers of liver fibrosis' requires
      measurement of liver fibrosis (and not liver biopsy stage scores). It is
      unacceptable for the words 'fibrosis' and 'score' to remain next to each other.
      There are benefits to properly understanding liver fibrosis and liver disease
      stage and properly assessing each of them.

PMID- 20812958
TI  - Effects of L-carnitine supplement on serum inflammatory cytokines, C-reactive
      protein, lipoprotein (a), and oxidative stress in hemodialysis patients with Lp
      (a) hyperlipoproteinemia.
AB  - Inflammation, oxidative stress, and high concentration of serum lipoprotein (a)
      [Lp (a)] are common complications in hemodialysis patients. The present study was
      designed to investigate the effects of L-carnitine supplement on serum
      inflammatory cytokines, C-reactive protein (CRP), Lp (a), and oxidative stress in
      hemodialysis patients with Lp (a) hyperlipoproteinemia [hyper Lp (a)]. This was
      an unblinded, randomized clinical trial. Thirty-six hyper Lp (a) hemodialysis
      patients (23 men and 13 women) were randomly assigned to either a carnitine or
      control group. Patients in the carnitine group received 1000 mg/d oral L
      carnitine for 12 weeks, whereas patients in the control group did not receive any
      L-carnitine supplement. At baseline and the end of week 12, 5 mL of blood were
      collected after a 12- to 14-hours fast and serum free carnitine, CRP, interleukin
      1beta, interleukin-6 (IL-6), tumor necrosis factor-alpha, Lp (a), and oxidized
      low-density lipoprotein were measured. Serum free carnitine concentration
      increased significantly by 86% in the carnitine group at the end of week 12
      compared with baseline (P<0.001), while serum CRP and IL-6 showed a significant
      decrease of 29% (P<0.05) and 61% (P<0.001), respectively. No significant changes
      were observed in serum free carnitine, CRP, and IL-6 in the control group. There
      were no significant differences between the two groups in mean changes of serum
      interleukin-1beta, tumor necrosis factor-alpha, Lp (a), and oxidized low-density
      lipoprotein concentrations. L-carnitine supplement reduces inflammation in
      hemodialysis patients, but has no effect on hyper Lp (a) and oxidative stress.

PMID- 20812960
TI  - Vitamin D-binding protein polymorphisms are not associated with development of
      (multiple) basal cell carcinomas.
AB  - Vitamin D-binding protein (VDBP) single nucleotide polymorphisms (SNP) may affect
      skin carcinogenesis. The objective was to test the association between two
      functional VDBP SNPs and the susceptibility to (multiple) basal cell carcinomas
      (BCCs). Of the 7983 participants, 5790 (72.5%) and 5823 (72.9%) participants were
      genotyped for rs7041 and rs4588, respectively, and three haplotypes (Gc1s, Gc2
      and Gc1f) were analysed. Two hundred and thirty-three persons developed a BCC of
      whom 122 (52.4%) developed multiple BCCs during a mean follow-up of 11.6 years.
      The VDBP genotype was not associated with (multiple) BCC development using Cox
      proportional hazards and Andersen-Gill analyses, respectively. Stratifying age
      groups demonstrated that in the youngest age-group, the A/T variant of rs7041 was
      associated with BCC development [adjusted hazard ratio (HR) = 1.88 (95%CI 1.10
      3.20)], while homozygote Gc1s carriers had a significantly lower BCC risk
      [adjusted HR = 0.53 (95%CI 0.31-0.91)]. In conclusion, the VDBP polymorphisms
      were not associated with susceptibility to (multiple) BCCs, but age-gene
      interactions were observed.

PMID- 20812959
TI  - High rate of fistula placement in a cohort of dialysis patients in a single payer
      system.
AB  - Arteriovenous fistulas (AVFs) are considered superior to arteriovenous grafts and
      catheters. Nevertheless, AVF prevalence in the United States remains under the
      established target. The complication rates and financial cost of vascular access
      continue to rise and disproportionately contribute to the burgeoning health care
      costs. The relationship between financial incentives for a type of vascular
      access and rate of access placement is unclear. All chronic hemodialysis patients
      (n=99) receiving care at Philadelphia Veterans Affairs Medical Center as of
      August 1, 2008 were participants. Demographic characteristics, vascular access
      type, and nonrelative value unit compensation were assessed as predictors, and
      the vascular access prevalence rate, operative times, and frequency of access
      interventions were analyzed. A 73.7% AVF rate was achieved in this cohort of
      patients with 51.5% diabetes mellitus. The number of access procedures per
      patient per year remained constant over time. The Philadelphia Veterans Affairs
      Medical Center, a single payer system, achieved superior AVF prevalence and
      exceeded the national AVF target. Financial incentives for arteriovenous graft
      placement currently exist in the United States, as there is similar Medicare
      reimbursement for arteriovenous graft and basilic vein transposition, despite
      longer operative times for basilic vein transpositions. The high AVF prevalence
      at the Philadelphia Veterans Affairs Medical Center may be due to the VA
      nonrelative value unit-driven system that allows for interdisciplinary care,
      priority of AVFs, and frequent use of basilic vein transposition surgery, when
      appropriate. We have identified an important, hypothesis-generating example of a
      nonrelative value unit-based approach to vascular access yielding superior
      results with respect to patient care and cost.

PMID- 20812961
TI  - Lysyl oxidase silencing impairs keratinocyte differentiation in a reconstructed
      epidermis model.
AB  - Lysyl Oxidase (LOX) is an extracellular enzyme involved in the maturation of
      connective tissues. It also acts in many cell types as a regulator of cell
      behaviour and phenotype through intracellular signalling pathways. Recently, LOX
      was shown to be present in human epidermis where its precise functions remain
      unclear. We showed here that in confluent monolayer cultures of normal human
      keratinocytes (KCs) and N/TERT-1-immortalized KCs, LOX expression was induced
      during the first differentiation steps. Moreover, the silencing of LOX by stable
      RNA interference disrupted the expression of early differentiation markers. In a
      reconstructed-epidermis model, LOX silencing did not impair the stratification
      process nor the formation of the first differentiated layers. However, terminal
      differentiation was strongly impaired, as shown by a decreased expression of late
      differentiation proteins and by the absence of stratum corneum. Nonetheless,
      inhibition of LOX enzymatic activity by beta-aminopropionitrile did not affect
      the differentiation process. Therefore, LOX protein acts during the first steps
      of KC differentiation and is important for subsequent commitment into terminal
      differentiation. Taken together, these results suggest that a finely regulated
      expression of LOX is necessary for normal KC differentiation and thus for
      maintenance of epidermal homeostasis.

PMID- 20812962
TI  - Primary human keratinocytes efficiently induce IL-1-dependent IL-17 in CCR6+ T
      cells.
AB  - Keratinocytes and activated T cells interact in skin inflammation by virtue of
      chemokines and cytokines. T cell-derived IL-17 has been described to play an
      important role in the course of psoriatic inflammation. In this study, we
      addressed how keratinocytes influence the secretion of IL-17 in autologous T cell
      subsets. We found that a co-culture of autologous keratinocytes and T cell
      receptor-stimulated T cells markedly enhanced the production of IL-17. Besides
      the importance of direct cell contact, this effect was mainly mediated by IL-1
      and could be blocked by the IL-1 antagonist anakinra. An additional increase in
      IL-17 production by IL-23 was only seen in the presence of IL-1, which thus plays
      a permissive role for the action of IL-23. Importantly, co-culture of
      keratinocytes with CCR6+ CD4+ T cells that are enriched for Th17 cells resulted
      in significantly higher IL-17 production compared to co-culture with CD4+ T
      cells.

PMID- 20812964
TI  - Negative regulation of stress-induced matrix metalloproteinase-9 by Sirt1 in skin
      tissue.
AB  - Solar ultra-violet (UV) radiation and the ensuing photo-damage are adverse
      factors affecting human skin directly exposed to the sun. Stress responses
      induced by UV radiation (UVR) elicit premature skin ageing (photoageing),
      resulting in extensive damage to dermal connective tissue. Disruption of the
      normal dermal structure of skin connective tissue, primarily collagen, impairs a
      variety of skin functions and is considered to be the main cause of wrinkle
      formation. Matrix metalloproteases (MMPs) may be responsible for the degradation
      of collagen and other extracellular matrix proteins, which are major targets for
      relieving skin photoageing. Herein, we demonstrated that Sirt1, a putative anti
      ageing enzyme, reduced MMP-9 transcriptional expression in skin. The known
      agonists of Sirt1, resveratrol and metformin, also significantly inhibited MMP-9
      expression and appeared to protect collagen from degradation after UVR. These
      studies suggest that the Sirt1 activator could be used as a novel therapeutic
      agent to delay skin photoageing.

PMID- 20812965
TI  - Protective effects of platinum nanoparticles against UV-light-induced epidermal
      inflammation.
AB  - Intracellular reactive oxygen species (ROS) and apoptosis play important roles in
      the ultraviolet (UV)-induced inflammatory responses in the skin. Metal
      nanoparticles have been developed to increase the catalytic activity of metals,
      which is because of the large surface area of smaller particles. Platinum
      nanoparticles (nano-Pt) protected by poly acrylic acid were manufactured by
      reduction with ethanol. A marked increase in ROS production was observed in UV
      treated HaCaT keratinocytes cell lines, while a decrease in ROS production was
      observed in nano-Pt-treated cells. Pretreatment of the cells with nano-Pt also
      caused a significant inhibition of UVB- and UVC-induced apoptosis. Furthermore,
      we found that mice treated with nano-Pt gel prior to UV irradiation showed
      significant inhibition of UVB-induced inflammation and UVA-induced photoallergy
      compared to UV-irradiated control mice. These results suggest that nano-Pt
      effectively protects against UV-induced inflammation by decreasing ROS production
      and inhibiting apoptosis in keratinocytes.

PMID- 20812966
TI  - Retinal and retinol are potential regulators of gene expression in the
      keratinocyte cell line HaCaT.
AB  - Vitamin A is a pivotal regulator of differentiation and growth of developing and
      adult skin. Retinoic acid is the major physiologically active form of vitamin A
      regulating the expression of different genes through retinoic acid nuclear
      receptors. Here, we present evidence that other vitamin A derivates - retinol and
      retinal - are also capable of functioning as regulators of gene expression in the
      keratinocyte cell line HaCaT. We have shown that all-trans retinol (ATRol) and
      all-trans retinal (ATRal) are capable of modulating gene expression in
      keratinocytes, which is not because of vitamin A metabolism in the cells, and
      retinol and retinal modulate gene expression through nuclear receptors: retinoic
      acid receptors (RARs) and retinoid X receptors (RXRs). Based on the data, we
      propose that ATRol and all-trans retinal, in addition to all-trans retinoic acid,
      can function as important regulators of gene expression manifesting their effect
      through the nuclear receptors RARs and RXRs.

PMID- 20812967
TI  - Aberrant demethylation of the recoverin gene is involved in the aberrant
      expression of recoverin in cancer cells.
AB  - The Ca(2+) -binding protein recoverin is normally specific for the retina.
      Recoverin aberrantly expressed in lung and melanoma tumors can trigger the host
      immune response followed by the development of a paraneoplastic neurological
      syndrome represented by cancer- and melanoma-associated retinopathy,
      respectively. The mechanisms, underlying the aberrant expression of recoverin in
      tumor cells, have remained unknown. The data obtained in this study suggest that
      (i) DNA methylation participates in the repression of synthesis of mRNA for
      recoverin in normal tissues and (ii) aberrant hypomethylation of the recoverin
      gene region, overlapping the promoter up-stream of the first exon and the first
      exon itself, is involved in the aberrant expression of recoverin in tumor cells.

PMID- 20812968
TI  - Modulation of metallothionein isoforms is associated with collagen deposition in
      proliferating keloid fibroblasts in vitro.
AB  - The keloid fibroblast (KF) is known to have higher proliferative capacity than
      normal dermal fibroblast (NF). Metallothionein (MT), a metal-binding protein, has
      been reported to promote cell proliferation. In this study, we evaluated the
      expression of MT isoforms at the mRNA level in fetal bovine serum (FBS)
      stimulated proliferating KF. Although the morphological appearance of NF and KF
      was similar when viewed under light, confocal and transmission electron
      microscopy, there was surprisingly a generally lower expression of MT isoforms in
      KF when compared with NF and also reduced MT staining in dermal fibroblasts of
      keloids as opposed to normal skin. Primary cultures of KF grown in 5% FBS or 10%
      FBS compared to without FBS demonstrated significantly higher proliferative
      activity and more abundant deposition of collagen. Contrary to expectation, MT
      1A, -1F, -1G, -1X and -2A isoforms were significantly down-regulated in
      proliferating KF. Moreover, stimulating KF with TGF beta1, which is known to
      promote collagen synthesis and keloid formation, increased expression of Collagen
      1A and 3A genes accompanied by reduction in MT-2A gene expression. Furthermore,
      down-regulation of the MT-2A gene in proliferating KF by siRNA-mediated silencing
      enhanced cell proliferation with concomitant up-regulation of the NF-kappaB gene
      and 10 of 13 other NF-kappaB pathway-related genes analysed but no alteration of
      the Collagen 1 and Collagen 3 gene expression. It would appear that down
      regulation of MT isoforms in proliferating KF, in particular MT-2A, enhances
      keloidogenesis with the possible involvement of the NF-kappaB signalling pathway.

PMID- 20812969
TI  - Quantitative detection of melanoma-associated antigens by multimarker real-time
      RT-PCR for molecular staging: results of a 5 years study.
AB  - INTRODUCTION: Monitoring of circulating melanoma cells in the peripheral blood is
      a promising method for identifying a subgroup of patients with minimal residual
      disease. OBJECTIVES: To evaluate the prognostic impact of melanoma-associated
      antigens by multimarker real-time RT-PCR for disease-specific survival time.
      METHODS: Five melanoma markers: Melan-A, gp 100, MAGE-3, MIA and tyrosinase were
      detected by a quantitative multimarker real-time reverse transcription-PCR (RT
      PCR). We included 65 patients with resected melanoma in stage II-III. Peripheral
      blood samples were examined every 3 months for 2 years. The expression of
      melanoma markers in 2925 RT-PCR assays was correlated with clinical staging
      results in total of 5 years. RESULTS: Twenty-seven patients relapsed during the
      study period and 26 of them revealed positive markers. MAGE-3 was the most
      sensitive progression marker in single occurrence or in combination with MIA and
      gp 100. The time distribution of metastases during the screened period was as
      follows: progression in the first year was observed in 40.7% patients, second
      year in 25.9%, third year in 18.6%, fourth and fifth year in 7.4% equally.
      CONCLUSIONS: Statistically significant tumor marker elevation during the first 2
      years after the surgical treatment correlates with a worse prognosis of patients.
      In contrast, the group showing negative real-time RT-PCR results in 24 months
      serial blood testing was associated with prolonged 5-year disease-specific
      survival. Therefore, quantitative detection of melanoma-specific molecular
      markers in the presented setting represents a useful tool for selecting patients
      in a higher risk of disease recurrence.

PMID- 20812972
TI  - Local adaptation, phenotypic differentiation, and hybrid fitness in diverged
      natural populations of Arabidopsis lyrata.
AB  - Selection for local adaptation results in genetic differentiation in ecologically
      important traits. In a perennial, outcrossing model plant Arabidopsis lyrata,
      several differentiated phenotypic traits contribute to local adaptation, as
      demonstrated by fitness advantage of the local population at each site in
      reciprocal transplant experiments. Here we compared fitness components,
      hierarchical total fitness and differentiation in putatively ecologically
      important traits of plants from two diverged parental populations from different
      continents in the native climate conditions of the populations in Norway and in
      North Carolina (NC, U.S.A.). Survival and number of fruits per inflorescence
      indicated local advantage at both sites and aster life-history models provided
      additional evidence for local adaptation also at the level of hierarchical total
      fitness. Populations were also differentiated in flowering start date and floral
      display. We also included reciprocal experimental F(1) and F(2) hybrids to
      examine the genetic basis of adaptation. Surprisingly, the F(2) hybrids showed
      heterosis at the study site in Norway, likely because of a combination of
      beneficial dominance effects from different traits. At the NC site, hybrid
      fitness was mostly intermediate relative to the parental populations. Local
      cytoplasmic origin was associated with higher fitness, indicating that
      cytoplasmic genomes also may contribute to the evolution of local adaptation.

PMID- 20812973
TI  - Adaptive evolution of plastron shape in emydine turtles.
AB  - Morphology reflects ecological pressures, phylogeny, and genetic and biophysical
      constraints. Disentangling their influence is fundamental to understanding
      selection and trait evolution. Here, we assess the contributions of function,
      phylogeny, and habitat to patterns of plastron (ventral shell) shape variation in
      emydine turtles. We quantify shape variation using geometric morphometrics, and
      determine the influence of several variables on shape using path analysis.
      Factors influencing plastron shape variation are similar between emydine turtles
      and the more inclusive Testudinoidea. We evaluate the fit of various evolutionary
      models to the shape data to investigate the selective landscape responsible for
      the observed morphological patterns. The presence of a hinge on the plastron
      accounts for most morphological variance, but phylogeny and habitat also
      correlate with shape. The distribution of shape variance across emydine phylogeny
      is most consistent with an evolutionary model containing two adaptive zones--one
      for turtles with kinetic plastra, and one for turtles with rigid plastra. Models
      with more complex adaptive landscapes often fit the data only as well as the null
      model (purely stochastic evolution). The adaptive landscape of plastron shape in
      Emydinae may be relatively simple because plastral kinesis imposes overriding
      mechanical constraints on the evolution of form.

PMID- 20812949
TI  - Predictors of bacterial pneumonia in Evaluation of Subcutaneous Interleukin-2 in
      a Randomized International Trial (ESPRIT).
AB  - BACKGROUND AND OBJECTIVES: Bacterial pneumonia still contributes to
      morbidity/mortality in HIV infection despite effective combination antiretroviral
      therapy (cART). Evaluation of Subcutaneous Interleukin-2 in a Randomized
      International Trial (ESPRIT), a trial of intermittent recombinant interleukin-2
      (rIL-2) with cART vs. cART alone (control arm) in HIV-infected adults with CD4
      counts >=300cells/MUL, offered the opportunity to explore associations between
      bacterial pneumonia and rIL-2, a cytokine that increases the risk of some
      bacterial infections. METHODS: Baseline and time-updated factors associated with
      first-episode pneumonia on study were analysed using multivariate proportional
      hazards regression models. Information on smoking/pneumococcal vaccination
      history was not collected. RESULTS: IL-2 cycling was most intense in years 1-2.
      Over ~7 years, 93 IL-2 [rate 0.67/100 person-years (PY)] and 86 control (rate
      0.63/100 PY) patients experienced a pneumonia event [hazard ratio (HR) 1.06; 95%
      confidence interval (CI) 0.79, 1.42; P=0.68]. Median CD4 counts prior to
      pneumonia were 570cells/MUL (IL-2 arm) and 463cells/MUL (control arm). Baseline
      risks for bacterial pneumonia included older age, injecting drug use, detectable
      HIV viral load (VL) and previous recurrent pneumonia; Asian ethnicity was
      associated with decreased risk. Higher proximal VL (HR for 1 log(10) higher VL
      1.28; 95% CI 1.11, 1.47; P<0.001) was associated with increased risk; higher CD4
      count prior to the event (HR per 100 cells/MUL higher 0.94; 95% CI 0.89, 1.0;
      P=0.04) decreased risk. Compared with controls, the hazard for a pneumonia event
      was higher if rIL-2 was received <180 days previously (HR 1.66; 95% CI 1.07,
      2.60; P=0.02) vs.>=180 days previously (HR 0.98; 95% CI 0.70, 1.37; P=0.9).
      Compared with the control group, pneumonia risk in the IL-2 arm decreased over
      time, with HRs of 1.41, 1.71, 1.16, 0.62 and 0.84 in years 1, 2, 3-4, 5-6 and 7,
      respectively. CONCLUSIONS: Bacterial pneumonia rates in cART-treated adults with
      moderate immunodeficiency are high. The mechanism of the association between
      bacterial pneumonia and recent IL-2 receipt and/or detectable HIV viraemia
      warrants further exploration.

PMID- 20812974
TI  - Evolutionary games in Wright's island model: kin selection meets evolutionary
      game theory.
AB  - This article studies evolutionary game dynamics in Wright's infinite island
      model. I study a general n * n matrix game and derive a basic equation that
      describes the change in frequency of strategies. A close observation of this
      equation reveals that three distinct effects are at work: direct benefit to a
      focal individual, kin-selected indirect benefit to the focal individual via its
      relatives, and the cost caused by increased kin competition in the focal
      individual's natal deme. Crucial parameters are the coefficient of relatedness
      between two individuals and its analogue for three individuals. I provide a
      number of examples and show when the traditional inclusive fitness measure is
      recovered and when not. Results demonstrate how evolutionary game theory fits
      into the framework of kin selection.

PMID- 20812975
TI  - Testing models of facultative sex ratio adjustment in the pollinating fig wasp
      Platyscapa awekei.
AB  - Female hymenoptera are renowned for their ability to adjust offspring sex ratio
      to local mate competition. When two females share a patch, they frequently
      produce clutches that differ in size, the female with the larger clutch optimally
      producing a more female-biased sex ratio and vice versa. Females can base their
      sex allocation on their own clutch size only ("self-knowledge") or on both
      females' clutch sizes ("complete knowledge"). Few studies have genotyped
      offspring so that each mother's contribution can be considered separately while
      none has found that both sources of information are used simultaneously. We
      genotyped 2489 wasps from 28 figs and assigned their maternity to one of the two
      foundress females. We argue that likelihood is a very convenient method to
      compare alternative models, while fitness calculations help to appreciate the
      cost of maladaptation. We find that the pollinating fig wasp Platyscapa awekei
      simultaneously uses its own as well as the other females clutch size in
      allocating sex. Indeed, the complete knowledge model explains the data 36 times
      better than the self-knowledge model. However, large clutches contained fewer
      males than the optimal predictions leading to a median selection coefficient of
      0.01.

PMID- 20812977
TI  - Origins and consequences of serpentine endemism in the California flora.
AB  - Habitat specialization plays an important role in the creation and loss of
      biodiversity over ecological and evolutionary time scales. In California,
      serpentine soils have a distinctive flora, with 246 serpentine habitat
      specialists (i.e., endemics). Using molecular phylogenies for 23 genera
      containing 784 taxa and 51 endemics, we infer few transitions out of the endemic
      state, which is shown by an analysis of transition rates to simply reflect the
      low frequency of endemics (i.e., reversal rates were high). The finding of high
      reversal rates, but a low number of reversals, is consistent with the widely
      hypothesized trade-off between serpentine tolerance and competitive ability,
      under which serpentine endemics are physiologically capable of growing in less
      stressful habitats but competitors lead to their extirpation. Endemism is also
      characterized by a decrease in speciation and extinction rates and a decrease in
      the overall diversification rate. We also find that tolerators (species with
      nonserpentine and serpentine populations) undergo speciation in serpentine
      habitats to give rise to new serpentine endemics but are several times more
      likely to lose serpentine populations to produce serpentine-intolerant taxa.
      Finally, endemics were younger on average than nonendemics, but this alone does
      not explain their low diversification.

PMID- 20812976
TI  - A model for genomic imprinting in the social brain: adults.
AB  - Genomic imprinting refers to genes that are silenced when inherited via sperm or
      via egg. The silencing of genes conditional upon their parental origin requires
      an evolutionary explanation. The most widely accepted theory for the evolution of
      genomic imprinting-the kinship theory-argues that conflict between maternally
      inherited and paternally inherited genes over phenotypes with asymmetric effects
      on matrilineal and patrilineal kin results in self-imposed silencing of one of
      the copies. This theory has been applied to imprinting of genes expressed in the
      placenta, and infant brain determining the allocation of parental resources being
      the source of conflict parental promiscuity. However, there is growing evidence
      that imprinted genes are expressed in the postinfant brain where parental
      promiscuity per se is no longer a source of conflict. Here, we advance the
      kinship theory by developing an evolutionary model of genomic imprinting in
      adults, driven by intragenomic conflict over allocation to parental versus
      communal care. We consider the role of sex differences in dispersal and variance
      in reproductive success as sources of conflict. We predict that, in hominids and
      birds, parental care will be expressed by maternally inherited genes. In
      nonhominid mammals, we predict more diversity, with some mammals showing the same
      pattern and other showing the reverse. We use the model to interpret experimental
      data on imprinted genes in the house mouse: specifically, paternally expressed
      Peg1 and Peg3 genes, underlying maternal care, and maternally expressed Gnas and
      paternally expressed Gnasxl genes, underlying communal care. We also use the
      model to relate ancestral demography to contemporary imprinting disorders of
      adults, in humans and other taxa.

PMID- 20812978
TI  - Evolution and creationism in Middle Eastern education: a new perspective.
AB  - Statements made in a recent outcry against a creationist in the Israeli Ministry
      of Education starkly illuminated Western misconceptions about Iranian science
      education. These misconceptions are perpetuated not only among the general public
      but also within the international scientific community, where investigations of
      "Islamic creationism" often incorporate misleading assumptions regarding Islamic
      religious attitudes toward science as well as the nature of secularism in non
      Western states. In turn, these assumptions have led to superficial analyses that
      overly rely on state religiosity to explain the treatment of evolution in
      national science education. Therefore, a new framework accounting for local
      political and social circumstances is crucial and urgently needed to effectively
      analyze science education in the Middle East.

PMID- 20812979
TI  - Size-fecundity relationships, growth trajectories, and the temperature-size rule
      for ectotherms.
AB  - Many ectotherms show crossing growth trajectories as a plastic response to
      rearing temperature. As a result, individuals growing up in cool conditions grow
      slower, mature later, but are larger at maturation than those growing up in warm
      conditions. To date, no entirely satisfactory explanation has been found for why
      this pattern, often called the temperature-size rule, should exist. Previous
      theoretical models have assumed that size-specific mortality rates were most
      likely to drive the pattern. Here, I extend one theoretical model to show that
      variation in size-fecundity relationships may also be important. Plasticity in
      the size-fecundity relationship has rarely been considered, but a number of
      studies show that fecundity increases more quickly with size in cold environments
      than it does in warm environments. The greater increase in fecundity offsets
      costs of delayed maturation in cold environments, favoring a larger size at
      maturation. This can explain many cases of crossing growth trajectories, not just
      in relation to temperature.

PMID- 20812984
TI  - Proteoglycans in health and disease: emerging concepts and future directions.

PMID- 20812985
TI  - Crystal structures of isomaltase from Saccharomyces cerevisiae and in complex
      with its competitive inhibitor maltose.
AB  - The structures of isomaltase from Saccharomyces cerevisiae and in complex with
      maltose were determined at resolutions of 1.30 and 1.60 A, respectively.
      Isomaltase contains three domains, namely, A, B, and C. Domain A consists of the
      (beta/alpha)(8) -barrel common to glycoside hydrolase family 13. However, the
      folding of domain C is rarely seen in other glycoside hydrolase family 13
      enzymes. An electron density corresponding to a nonreducing end glucose residue
      was observed in the active site of isomaltase in complex with maltose; however,
      only incomplete density was observed for the reducing end. The active site pocket
      contains two water chains. One water chain is a water path from the bottom of the
      pocket to the surface of the protein, and may act as a water drain during
      substrate binding. The other water chain, which consists of six water molecules,
      is located near the catalytic residues Glu277 and Asp352. These water molecules
      may act as a reservoir that provides water for subsequent hydrolytic events. The
      best substrate for oligo-1,6-glucosidase is isomaltotriose; other, longer-chain,
      oligosaccharides are also good substrates. However, isomaltase shows the highest
      activity towards isomaltose and very little activity towards longer
      oligosaccharides. This is because the entrance to the active site pocket of
      isomaltose is severely narrowed by Tyr158, His280, and loop 310-315, and because
      the isomaltase pocket is shallower than that of other oligo-1,6-glucosidases.
      These features of the isomaltase active site pocket prevent isomalto
      oligosaccharides from binding to the active site effectively.

PMID- 20812987
TI  - Comparative proteomic analysis identifies proteins associated with the
      development and progression of colorectal carcinoma.
AB  - To better understand the mechanism underlying colorectal carcinoma (CRC) genesis
      or metastasis, and to search for potential markers for CRC prognosis, a
      comparative proteomic analysis was performed on CRC tissue. Proteins were
      extracted from normal colorectal mucosa, non-metastatic CRC (nmCRC) and
      metastatic CRC (mCRC) tissue samples. Protein profiling of each sample was
      performed by two-dimensional electrophoresis coupled with MALDI-TOF MS, followed
      by confirmation by Western blotting. Thirty-one proteins were found to be
      differentially expressed between normal mucosa, nmCRC and mCRC tissue. In 126
      paraffin-embedded CRC samples, three differentially expressed proteins,
      identified as LASP-1, S100A9 and RhoGDI by proteomic analysis, were detected by
      immunohistochemical staining to determine the clinicopathological characteristics
      of these proteins in CRC. Increased expression levels of these proteins were
      found in CRC, especially mCRC, compared with normal mucosa. The results provide
      the basis for searching for potential markers for CRC genesis and metastasis, and
      also provide clues for elucidating the mechanism of CRC progression. The pattern
      changes identified have the potential to be used for the design of marker panels
      for assistance in diagnostic and therapeutic strategies in CRC.

PMID- 20812991
TI  - Hand disinfection in hospitals - benefits and risks.
AB  - The WHO regards hand hygiene as an essential tool for the prevention of noso
      comial infections. The hygienic hand disinfection has a superior antimicrobial
      efficacy compared to hand washing and should be performed as the treatment of
      choice before and after a variety of activities at the point of patient care.
      Washing hands should be preferred when the hands are visibly soiled. Skin
      irritation is quite common among healthcare workers and is mainly caused by
      water, soap and long lasting occlusion. Compliance with hand disinfection in
      clinical practice is often low. Measures to improve compliance include training,
      provision of hand rubs where they are needed, and the responsibility of doctors
      to set a good example. Improved compliance in hand hygiene and targeted use of
      alcohol-based hand rubs can reduce the nosocomial infection rate by up to 40 %.
      The benefit of hand disinfection is therefore much larger than possible risks.

PMID- 20812992
TI  - Successful immunoapheresis of bullous autoimmune diseases: pemphigus vulgaris and
      pemphigoid gestationis.
AB  - BACKGROUND: Immunoapheresis/immunoadsorption is a specific tool to remove
      immunoglobulins and immune complexes from the circulation. Immunoapheresis is
      successfully used in various autoantibody-mediated diseases (such as autoimmune
      renal disease and others). In dermatology immunoapheresis is increasingly applied
      as an adjuvant treatment for severe autoimmune bullous diseases. CASE REPORT: We
      successfully employed adjuvant immunoapheresis to treat a 57-year-old man with
      life-threatening pemphigus vulgaris and a 30-year-old pregnant woman with severe
      pemphigoid gestationis. Immunoapheresis induced a rapid improvement and almost
      complete clearance of clinical symptoms without notable side effects. The
      clinical improvement was paralleled by a decline of the pathologic circulating
      autoantibodies. Following stabilization of his disease with immunoapheresis, the
      pemphigus vulgaris patient was continued on rituximab and remained almost free of
      symptoms for the next 12 months. The patient with pemphigoid gestationis was
      subsequently treated with systemic corticosteroids until the symptoms of her self
      limited disease ceased. CONCLUSION: Immunoapheresis might represent an excellent
      therapy for certain patients with severe pemphigus vulgaris or pemphigoid
      gestationis, unresponsive to conventional treatment regimens. We observed rapid
      improvement of clinical symptoms and no notable side effects.

PMID- 20812993
TI  - Nickel on the Swedish market: follow-up 10 years after entry into force of the EU
      Nickel Directive.
AB  - BACKGROUND: The EU Nickel Directive, aimed at primary and secondary prevention of
      nickel allergy by limitation of nickel release from certain items, came fully
      into force in July 2001. OBJECTIVES: To assess the prevalence on the market of
      items with nickel release and to compare the outcome with previous studies
      performed in Sweden in 1999 and 2002-2003. MATERIALS AND METHODS: Nickel release
      from 659 items covered by the EU Nickel Directive was assessed with the
      dimethylglyoxime (DMG) test. Special attention, as compared with the previous
      surveys, was given to cheap jewellery in street markets and sewing materials in
      haberdashery shops. RESULTS: Nickel release was shown for 9% of the tested items,
      all of which were intended for direct and prolonged contact with the skin. A high
      proportion of items bought at haberdashery shops and street markets, 34% and 61%,
      respectively, showed nickel release. CONCLUSIONS: The Swedish market for products
      intended for direct and prolonged contact with the skin has largely adapted to
      the Nickel Directive. It is suggested that authorities should monitor the market
      regularly and give attention to areas where compliance with the requirements is
      poor, for protection of public health.

PMID- 20812994
TI  - Approaches to characterizing Entamoeba histolytica transcriptional regulation.
AB  - Entamoeba histolytica causes an estimated 100,000 deaths per year and is one of
      the leading causes of death among parasitic infections. Studies using E.
      histolytica-specific polymerase chain reaction identified that 13.8% of adults in
      a rural Mexican community and 11.2% of adults in central Vietnam are
      asymptomatically colonized. Such high incidents of asymptomatic infection suggest
      that only a minority of infections proceed to invasive disease. Understanding the
      mechanisms that underpin variable disease outcome will be critical in developing
      therapeutic strategies. In recent years there have been a plethora of gene
      expression profiling data documenting the transcriptome differences between
      virulent and non-virulent strains of E. histolytica as well as changes induced by
      external environmental changes or stimuli. While these studies have successfully
      identified co-regulated genes and potential virulence factors, there is still
      little known about the transcriptional mechanisms that induce the changes
      observed in this non-model organism. In this review, we have looked at how
      molecular technological advances have shaped our understanding of transcriptional
      regulation in amoeba and what we may expect from the application of powerful new
      techniques.

PMID- 20812995
TI  - Cell wall integrity and high osmolarity glycerol pathways are required for
      adaptation of Alternaria brassicicola to cell wall stress caused by brassicaceous
      indolic phytoalexins.
AB  - Camalexin, the characteristic phytoalexin of Arabidopsis thaliana, inhibits
      growth of the fungal necrotroph Alternaria brassicicola. This plant metabolite
      probably exerts its antifungal toxicity by causing cell membrane damage. Here we
      observed that activation of a cellular response to this damage requires cell wall
      integrity (CWI) and the high osmolarity glycerol (HOG) pathways. Camalexin was
      found to activate both AbHog1 and AbSlt2 MAP kinases, and activation of the
      latter was abrogated in a AbHog1 deficient strain. Mutant strains lacking
      functional MAP kinases showed hypersensitivity to camalexin and brassinin, a
      structurally related phytoalexin produced by several cultivated Brassica species.
      Enhanced susceptibility to the membrane permeabilization activity of camalexin
      was observed for MAP kinase deficient mutants. These results suggest that the two
      signalling pathways have a pivotal role in regulating a cellular compensatory
      response to preserve cell integrity during exposure to camalexin. AbHog1 and
      AbSlt2 deficient mutants had reduced virulence on host plants that may, at least
      for the latter mutants, partially result from their inability to cope with
      defence metabolites such as indolic phytoalexins. This constitutes the first
      evidence that a phytoalexin activates fungal MAP kinases and that outputs of
      activated cascades contribute to protecting the fungus against antimicrobial
      plant metabolites.

PMID- 20812996
TI  - Thickness of the middle trapezius muscle measured by rehabilitative ultrasound
      imaging: description of the technique and reliability study.
AB  - A technique is described for measuring the thickness of the middle trapezius
      muscle using rehabilitative ultrasound imaging (RUSI). A test-retest study was
      employed to investigate the reliability of the technique in a convenience sample
      of 16 asymptomatic participants aged 20-41 (12 women). The middle trapezius
      muscle was imaged using RUSI with participants in a standardized sitting
      position. The principal investigator took measurements on two consecutive days to
      examine intra-rater reliability, and two additional investigators took
      measurements on the second day to investigate inter-rater reliability of the
      measurement technique. Reliability was examined using intra-class correlation
      coefficients (ICC), standard error of measurement (SEM), and Bland and Altman
      plots. The results demonstrated that inter-rater reliability was good between
      raters (ICC2,3 = 0.81, SEM = 0.94 mm) and was moderate for the same rater between
      days (ICC3,2 = 0.67, SEM = 1.0 mm). This study demonstrates that RUSI can be used
      reliably to measure muscle thickness of the middle trapezius muscle following the
      procedure described.

PMID- 20812997
TI  - Comparison of familial and sporadic chronic lymphocytic leukaemia using high
      resolution array comparative genomic hybridization.
AB  - Approximately 10% of patients with chronic lymphocytic leukaemia (CLL) have a
      family history of the disease or a related lymphoproliferative disorder, yet the
      relationship of familial CLL to genomic abnormalities has not been characterized
      in detail. We therefore studied 75 CLL patients, half familial and half sporadic,
      using high-resolution array comparative genomic hybridization (CGH), in order to
      better define the relationship of genomic abnormalities to familial disease and
      other biological prognostic factors. Our results showed that the most common high
      risk deletion in CLL, deletion 11q, was significantly associated with sporadic
      disease. Comparison of familial to sporadic disease additionally identified a
      copy number variant region near the centromere on 14q, proximal to IGH@, in which
      gains were associated both with familial CLL, and with mutated IGHV and
      homozygous deletion of 13q. Homozygous deletion of 13q was also found to be
      associated with mutated IGHV and low expression of ZAP-70, and a significantly
      longer time to first treatment compared to heterozygous deletion or lack of
      alteration. This study is the first high resolution effort to investigate and
      report somatic genetic differences between familial and sporadic CLL.

PMID- 20812998
TI  - Detection of antibodies against human platelet antigens 15a and 15b by using a
      cell line panel.

PMID- 20812999
TI  - A European consensus report on blood cell identification: terminology utilized
      and morphological diagnosis concordance among 28 experts from 17 countries within
      the European LeukemiaNet network WP10, on behalf of the ELN Morphology Faculty.
AB  - This paper describes the methodology used to develop a consensual glossary for
      haematopoietic cells within Diagnostics-WP10 of European-LeukemiaNet EU-project.
      This highly interactive work was made possible through the use of the net,
      requiring only a single two-day meeting of actual confrontation and debate. It
      resulted in the production of a freely accessible tool that could be useful for
      training as well as harmonization of morphological reports in onco-haematology
      especially, without geographic limitation, not limited to European countries.
      Moreover, this collective work resulted in the production of a consensus
      statement, taking into account individual practices, collegial agreement and
      literature data.

PMID- 20813001
TI  - Selection of reference genes for quantitative polymerase chain reaction studies
      in purified B cells from B cell chronic lymphocytic leukaemia patients.
AB  - The clinical heterogeneity of B-cell chronic lymphocytic leukaemia (B-CLL) makes
      it necessary to identify potent prognostic indicators to predict individual
      clinical course and select risk-adapted therapy. In recent years, numerous gene
      expression models have been suggested as prognostic factors of B-CLL. Today,
      quantitative polymerase chain reaction (qPCR) is a preferred method for rapid
      quantification of gene expression and validation of microarray data. The
      reliability of qPCR data is highly dependent on the use of appropriate reference
      genes for normalization. To date, no validated reference genes have been reported
      for the normalization of gene expression in B-CLL. Therefore, the present study
      was conducted to identify suitable reference genes for gene expression studies in
      CD19(+) B cells isolated from B-CLL patients' peripheral blood. The stability of
      ACTB, B2M, GAPDH, GUSB, HMBS, HPRT1, MRPL19, TBP and UBC genes was determined by
      three different descriptive statistics, geNorm, NormFinder and BestKeeper-1,
      which produced highly comparable results. Based on our results, B2M, HPRT1, and
      GUSB were found to be the most suitable reference genes for qPCR studies in B-CLL
      patients' peripheral blood B cells.

PMID- 20813000
TI  - Polymorphisms in DNA repair genes and risk of non-Hodgkin lymphoma in a pooled
      analysis of three studies.
AB  - Genetic variations in DNA repair genes are thought to play an important role in
      the pathogenesis and development of non-Hodgkin lymphoma (NHL). To further
      explore this hypothesis, we genotyped 319 tag single nucleotide polymorphisms
      (SNPs) in 27 DNA repair gene regions in 1946 cases and 1808 controls pooled from
      three population-based case-control studies of NHL in the US and Australia.
      Relative risks of NHL and NHL subtypes in relation to SNP genotypes were assessed
      using logistic regression. Associations of gene regions and pathways with NHL or
      NHL subtypes were explored using the minP and tail-strength statistics,
      respectively. Overall, genetic polymorphisms within the DNA repair pathway were
      associated with NHL (P = 0.005). Similar associations were seen with the double
      strand break repair (P = 0.02) and nucleotide excision repair (P = 0.04)
      pathways. Five SNPs (BLM rs441399, RAD50 rs2237060, FAM82A2 rs2304583, ERCC3
      rs4150506, and XRCC4 rs13178127) were particularly noteworthy because their gene
      regions were significantly associated with NHL or NHL subtypes (minP <= 0.05), or
      because of high level of statistical significance (P <= 0.005) and consistent
      findings across the three studies. These results support the hypothesis that
      common genetic polymorphisms in human DNA repair genes may modify the risk of
      NHL.

PMID- 20813003
TI  - Seizures in the Jamaica cohort study of sickle cell disease.
AB  - Although there is some evidence that epilepsy is more common in Sickle Cell
      Disease (SCD), we sought to establish the incidence rates, risk factors for and
      specific types of seizures in a SCD cohort followed from birth, and how seizure
      occurrence affects morbidity and mortality. We examined all records of persons in
      the Jamaica cohort Study of Sickle Cell Disease (JSSCD) clinically identified as
      having experienced a seizure during their lifetime. At first presentation,
      seizures were classified as Febrile Convulsion, Acute Symptomatic Seizure or
      Single Unprovoked Seizure. The seizure classification was revised to include
      Epilepsy if seizures recurred. Thirty-eight persons in the JSSCD (N = 543) were
      identified with seizures. The 5-year cumulative incidence of febrile convulsions
      was 2.2%. The incidence rate of epilepsy (all genotypes) was 100/100 000 person
      years, 139/100 000 for the SS genotype. Despite limited availability of
      diagnostic investigations, clinical seizures were associated with increased all
      cause mortality. Male gender (Odds Ratio [OR]: 4.0[95% confidence interval [CI];
      1.03-20.0]) and dactylitis in childhood (OR: 17.4 [95% CI; 4.82-62.85]) were
      associated with increased risk of developing epilepsy. Epilepsy in persons with
      SCD is 2-3 times more common than in non-sickle populations and is associated
      with increased all-cause mortality in all sickle cell genotypes.

PMID- 20813002
TI  - Desmoplakin and KIF20B as target antigens in patients with paroxysmal nocturnal
      haemoglobinuria.
AB  - At least two hypotheses have been proposed to explain the mechanism of clonal
      expansion of mutant cells in paroxysmal nocturnal haemoglobinuria (PNH). One
      hypothesis assumes an immune escape mechanism and another proposes an intrinsic
      second mutational event within clonal cells. We hypothesised that autoantibodies
      detected in PNH patients could identify antigens that might play a role in the
      pathophysiology of this disease and screened a human fetal liver cDNA library for
      serological reactivity against haematopoietic stem/progenitor cells antigens
      using the SEREX approach. Two antigens were identified that are constitutively
      expressed in CD34(+) cells. Three and four of 10 PNH patients showed antibody
      responses against kinesin family member 20B (KIF20B) (previously termed M-phase
      phosphoprotein 1, MPP1) and desmoplakin (DSP) respectively. We also found an
      antibody response in one of 20 healthy volunteers against desmoplakin, yet at a
      much lower titre than in PNH patients. No response to KIF20B or desmoplakin was
      detected in five patients with aplastic anaemia without a glycosyl phosphatidyl
      inositol -deficient clone. We conclude that KIF20B and desmoplakin have been
      shown to be the first known auto-antigens to be recognised by the immune system
      of patients with PNH. The analysis of the mechanisms underlying the autoimmune
      response might contribute to our understanding of the clonal expansion in PNH.

PMID- 20813004
TI  - Engagement of CD31 delivers an activating signal that contributes to the survival
      of chronic lymphocytic leukaemia cells.
AB  - The present study showed that engagement of CD31 delivers a survival signal in
      chronic lymphocytic leukaemia (CLL) cells. We describe two groups of CLL, showing
      different kinetics of apoptosis in vitro and distinct ratios between anti
      apoptotic and pro-apoptotic proteins: CLL-I displayed low Bcl-x(L) /Bax and Bcl
      2/Bax ratio and underwent rapid apoptosis in vitro; CLL-II had high Bcl-x(L) /Bax
      and Bcl-2/Bax ratio and were resistant to apoptosis for several days. Nurse-like
      cells, expressing vimentin, CD68 and CD31 were detected mainly in CLL-II
      cultures. Of note, CD31 cross-linking, obtained with a specific monoclonal
      antibody (mAb), induced phosphatidylinositol-3-kinase-dependent Akt
      phosphorylation and nuclear translocation of the nuclear factor-kBp65 and p52
      subunits in both CLL groups, leading to upregulation of Bcl-2 and Bcl-x(L)
      transcription and increased cell survival. Binding to CD31(+) stable
      transfectants, could also deliver an anti-apoptotic signal in B cells of both CLL
      I and CLL-II, increasing the Bcl-2 and Bcl-x(L) protein content, regardless the
      expression of CD38. On the other hand, the addition of the F(ab')2 (that is
      unable to oligomerize the target molecule) of the anti-CD31 mAb prevented these
      effects. These data suggest that the CD31 adhesion system may play a role also in
      vivo in maintaining CLL survival.

PMID- 20813006
TI  - Volume-perfusion CT as an adjunct to whole-body contrast-enhanced CT for
      monitoring response to therapy in lymphoma.

PMID- 20813005
TI  - Genomic lesions associated with a different clinical outcome in diffuse large B
      Cell lymphoma treated with R-CHOP-21.
AB  - Despite recent therapeutic improvements, the clinical course of diffuse large B
      cell lymphoma (DLBCL) still differs considerably among patients. We conducted
      this retrospective multi-centre study to evaluate the impact of genomic
      aberrations detected using a high-density genome wide-single nucleotide
      polymorphism-based array on clinical outcome in a population of DLBCL patients
      treated with R-CHOP-21 (rituximab, cyclophosphamide, doxorubicine, vincristine
      and prednisone repeated every 21 d). 166 DNA samples were analysed using the
      GeneChip Human Mapping 250K NspI. Genomic anomalies were analysed regarding their
      impact on the clinical course of 124 patients treated with R-CHOP-21.
      Unsupervised clustering was performed to identify genetically related subgroups
      of patients with different clinical outcomes. Twenty recurrent genetic lesions
      showed an impact on the clinical course. Loss of genomic material at 8p23.1
      showed the strongest statistical significance and was associated with additional
      aberrations, such as 17p- and 15q-. Unsupervised clustering identified five DLBCL
      clusters with distinct genetic profiles, clinical characteristics and outcomes.
      Genetic features and clusters, associated with a different outcome in patients
      treated with R-CHOP, have been identified by arrayCGH.

PMID- 20813007
TI  - NOTCH1 PEST domain mutation is an adverse prognostic factor in B-CLL.

PMID- 20813008
TI  - Cardiac magnetic resonance in transfusion dependent thalassaemia: assessment of
      iron load and relationship to left ventricular ejection fraction.
AB  - Cardiac Magnetic Resonance (CMR) has replaced all other surrogate measurements in
      the determination of transfusional cardiac iron overload in patients with
      thalassaemia major. We aimed to determine the diagnostic value of CMR T2* with
      respect to cardiac dysfunction (CD) as determined by CMR-derived left ventricular
      ejection fraction (LVEF). Cardiac T2* values and LVEF measured by CMR were
      recorded in 303 patients with thalassaemia major, at the time of their first CMR.
      T2* was correlated with LVEF (regression coefficient: 0.57, P<0.001). The
      prevalence of CD was 32.9% in patients with T2*<=8 ms, 12.5% in patients with
      T2*>8 ms and <=14 ms and reduced to 9.1% in patients with T2* between 14-20 ms.
      As the probability of CD is progressively, and not suddenly, reduced with
      increasing values of T2*, CMR has a limited diagnostic value for CD (Receiver
      operating characteristic analysis, area under the curve = 0.68). Patients with
      cardiac T2*<=8 ms require careful and intensive management. This risk decreases
      with increasing values of T2* but even in mildly loaded patients the probability
      of impaired LVEF is not negligible.

PMID- 20813009
TI  - Silencing of ROR1 and FMOD with siRNA results in apoptosis of CLL cells.
AB  - We have previously demonstrated that ROR1 and FMOD (fibromodulin) are two genes
      upregulated in chronic lymphocytic leukaemia (CLL) cells compared to normal blood
      B cells. In this study, siRNAs were used to specifically silence ROR1 and FMOD
      expression in CLL cells, healthy B cells and human fibroblast cell lines. siRNA
      treatment induced a specific reduction (75-95%) in FMOD and ROR1 mRNA. Western
      blot analysis with specific antibodies for FMOD and ROR1 demonstrated that the
      proteins were significantly downregulated 48 h after siRNA treatment. Silencing
      of FMOD and ROR1 resulted in statistically significant (P <= 0.05-0.001)
      apoptosis of CLL cells but not of B cells from normal donors. Human fibroblast
      cell lines treated with FMOD and ROR1 siRNA did not undergo apoptosis. This is
      the first report demonstrating that ROR1 and FMOD may be involved in the survival
      of CLL cells. ROR1 in particular is further explored as potential target for
      therapy in CLL.

PMID- 20813010
TI  - Recent advances in the understanding of genetic defects of neutrophil number and
      function.
AB  - Neutrophils are amongst the first immune cells to arrive at sites of infection
      and play an important role as the host's first line of defence against invading
      pathogens. Defects of neutrophil number or function are usually recognized
      clinically by recurrent infections that often are life-threatening. Over the last
      few years, a number of genetic mutations have been discovered to be the basis for
      congenital neutropenia, adding to our understanding of the molecular basis of
      these diseases. While many genetic mutations that cause severe congenital
      neutropenia result in a differentiation block at the promyelocyte stage, defects
      of neutrophil function are more heterogeneous on clinical, genetic and
      mechanistic levels. In this review we discuss recent advances in our
      understanding of the genetic and molecular basis of human neutrophil disorders.

PMID- 20813011
TI  - Leukaemic alveolar rhabdomyosarcoma.

PMID- 20813013
TI  - Platanus pollen allergen, Pla a 1: quantification in the atmosphere and influence
      on a sensitizing population.
AB  - BACKGROUND: The allergic response in susceptible patients does not always
      coincide with the presence and magnitude of airborne pollen counts. The
      prevalence of allergy to Platanus is currently moderate, although the percentage
      of monosensitized patients is low. This hinders accurate interpretation of the
      relationship between the amount of pollen inhaled and the patient's symptoms.
      OBJECTIVE: This study aims to investigate the relationship between the
      atmospheric concentration pattern of Pla a 1 aeroallergen and the Platanus
      pollen. METHODS: The pollen sampling was carried out using a Hirst-type
      volumetric trap (Burkard((c)) ) for pollen grains and a Burkard Cyclone sampler
      (Burkard((c)) ) for Pla a 1 allergen. Serum-specific IgE levels to Acer sp.,
      Artemisia vulgaris, Betula alba, Chenopodium album, Cupressus arizonica, Cynodon
      dactylon, Fraxinus excelsior, Lolium perenne, Pinus sp., Plantago lanceolata,
      Platanus acerifolia, Populus sp., Quercus ilex and Taraxacum officinale allergens
      were determined using the EAST System (Hytec specific IgE EIA kit; Hycor
      Biomedical, Kassel, Germany). RESULTS: The aerobiological dynamics of Platanus
      pollen grains and Pla a 1 differed considerably, particularly during the Platanus
      pollination period. Of the 118 subjects tested, sera from 34 contained specific
      IgE to Platanus pollen and all of them had specific IgE to other pollen types.
      CONCLUSIONS: The presence of the aeroallergen Pla a 1 in the atmosphere appears
      to be independent of Platanus pollen counts over the same period, which may be
      contributing to allergic symptoms and sensitization. The number of polysensitized
      patients displaying allergy to Platanus suggested that allergic symptoms were
      caused by co-sensitization or cross-reactivity involving a number of allergenic
      particles.

PMID- 20813014
TI  - Poly (gamma, L-glutamic acid)-cisplatin bioconjugate exhibits potent antitumor
      activity with low toxicity: a comparative study with clinically used platinum
      derivatives.
AB  - We have recently synthesized a new platinum derivative, poly (gamma, L-glutamic
      acid)-cisplatin conjugate (gamma-PGA-CDDP), and shown that it displayed
      remarkable antitumor activity against breast tumor in a mouse model. The purpose
      of this study is to systematically compare this new drug with three platinum
      derivatives currently used in the clinic: cisplatin, carboplatin and oxaliplatin.
      Here, we show that gamma-PGA-CDDP displays impressive antitumor activity over the
      current clinically used platinum drugs. More interestingly and more importantly,
      gamma-PGA-CDDP conjugate significantly reduces cytotoxicity, mitigates oxidative
      stress and improves antioxidative capability in vivo. Animals treated with gamma
      PGA-CDDP display the same profile of body weight as the control animals, while
      the tumors in gamma-PGA-CDDP-treated animals are significantly suppressed
      compared with those treated with carboplatin and oxaliplatin. Our data suggest
      that gamma-PGA could be used as an effective carrier for drug delivery and that
      gamma-PGA-CDDP conjugate may have potential therapeutic applications in human
      cancers that are sensitive to treatment with CDDP-based chemotherapy such as
      ovarian cancer.

PMID- 20813012
TI  - Targeting paediatric acute lymphoblastic leukaemia: novel therapies currently in
      development.
AB  - Modifications to the treatment of acute lymphoblastic leukaemia (ALL) in children
      have led to a dramatic increase in survival in the past 40 years. Despite this
      success, a significant subset of paediatric leukaemia patients either relapse or
      fail to ever achieve a complete remission. Additionally, some patients
      necessitate treatment with intensified chemotherapy regimens due to clinical or
      laboratory findings which identify them as high risk. These patients are unlikely
      to respond to further minor adjustments to the dosing or timing of administration
      of the same chemotherapy medications. Many novel targeted therapies for the
      treatment of childhood ALL provide potential mechanisms to further improve cure
      rates, and provide the possibility of minimizing toxicity to non-malignant cells,
      given their specificity to malignant cell phenotypes. This article explores many
      of the potential targeted therapies in varying stages of development, from those
      currently in clinical trials to those still being refined in the research
      laboratory.

PMID- 20813015
TI  - Efficacy of ketogenic diet in severe refractory status epilepticus initiating
      fever induced refractory epileptic encephalopathy in school age children (FIRES).
AB  - PURPOSE: Fever induced refractory epileptic encephalopathy in school age children
      (FIRES) is a devastating condition initiated by prolonged perisylvian refractory
      status epilepticus (SE) triggered by fever of unknown cause. SE may last more
      than 1 month, and this condition may evolve into pharmacoresistant epilepsy
      associated with severe cognitive impairment. We aimed to report the effect of
      ketogenic diet (KD) in this condition. METHODS: Over the last 12 years we
      collected data of nine patients with FIRES who received a 4:1 ratio of fat to
      combined protein and carbohydrate KD. They presented with SE refractory to
      conventional antiepileptic treatment. RESULTS: In seven patients, KD was
      efficacious within 2-4 days (mean 2 days) following the onset of ketonuria and 4
      6 days (mean 4.8 days) following the onset of the diet. In one responder, early
      disruption of the diet was followed by relapse of intractable SE, and the patient
      died. Epilepsy affected the other six responders within a few months. DISCUSSION:
      KD may be an alternative therapy for refractory SE in FIRES and might be proposed
      in other types of refractory SE in childhood.

PMID- 20813017
TI  - Trace elements in nails as biomarkers in clinical research.
AB  - BACKGROUND: The importance of trace elements in relation to human health has been
      increasingly recognized. Accurate and adequate quantification of trace elements
      are crucial in clinical research. DESIGN: This review was to discuss the
      rationale of using nail trace elements as biomarkers in clinical studies.
      RESULTS: For most trace elements, dietary instruments cannot appropriately
      capture the intakes because of the minimal amounts and wide variations in the
      same foods grown in different area as well as the nondietary exposures.
      Therefore, biomarkers may be essential in studying trace elements. Although there
      are notable differences among trace elements in the availability of biomarkers,
      increasing evidence supports that nails, particularly toenail concentrations of
      most trace elements, are useful biomarkers of exposure in which a single sample
      is assumed to represent long-term exposure. CONCLUSIONS: Compared with other
      potential biomarkers of trace elements, nail measurement has certain advantages
      in clinical research.

PMID- 20813018
TI  - Suicide risk in adolescents with chronic illness: implications for primary care
      and specialty pediatric practice: a review.
AB  - Suicide in adolescents is a global tragedy. Research-identified correlates of
      suicide in youth include depression, academic failure, loss of friends, social
      isolation, and substance abuse, among others. This review focuses on the
      potential link between chronic illness in adolescents and increased suicide risk.
      Research suggests that chronic illness is a risk factor for depression in
      adolescents that may induce suicide ideation and attempts; however, this risk may
      be increased even more in young adulthood if the underlying causes of depression
      are not resolved. This risk needs to be considered against the research data
      noting an increase in suicide attempts and completions, in each decade of life
      from adolescence into adulthood. Although more research is clearly needed, it can
      be concluded that suicide risks are seen in adolescents with chronic illness and
      all of these young people should be screened for depression and other risk
      factors for suicide on a regular basis.

PMID- 20813019
TI  - The effectiveness of task-oriented intervention and trunk restraint on upper limb
      movement quality in children with cerebral palsy.
AB  - AIM: The goal of this study was to contribute evidence towards the effectiveness
      of task-oriented training with and without restriction of trunk movement (trunk
      restraint) on the quality of upper limb movement in children with cerebral palsy
      (CP). METHOD: We used a prospective, single-subject research design in 12
      children (three males, nine females; aged 6-11 y; median 9 y) with di-, hemi-, or
      quadriplegia. Movements of the most affected arm were assessed five times: three
      times before training, immediately after training, and 3 months after training.
      The main outcome measures were the Melbourne Assessment of Unilateral Upper Limb
      Function (Melbourne) and upper limb movement kinematics during a functional
      reaching task. Children were randomly allocated to one of two groups: task
      oriented training with or without trunk restraint. Treatment consisted of three 1
      hour sessions per week for 5 weeks (total training duration 15 h). Treatment
      effects were determined using single-subject research design analysis--regression
      through baseline data and standard mean differences. RESULTS: Although the
      Melbourne scores were largely unchanged after training, some children in each
      group improved arm trajectory smoothness (effect size 0.55-1.87), and most
      children improved elbow extension range (effect size 0.55-4.79). However, more
      children in the trunk restraint group than in the no restraint group demonstrated
      reduced trunk displacement (effect size 0.94-2.25) and longer-term improvements
      in elbow extension and trunk use. Among the group who underwent training without
      trunk restraint, trunk displacement was unchanged or increased, and fewer carry
      over effects were apparent at follow-up. INTERPRETATION: This proof-of-principle
      study showed that greater improvement in the quality of upper limb movement in
      children with CP, including less compensatory trunk use and better carry-over
      effects, was achieved by training with trunk restraint.

PMID- 20813020
TI  - Oromotor dysfunction and communication impairments in children with cerebral
      palsy: a register study.
AB  - AIM: to report the prevalence, clinical associations, and trends over time of
      oromotor dysfunction and communication impairments in children with cerebral
      palsy (CP). METHOD: multiple sources of ascertainment were used and children
      followed up with a standardized assessment including motor speech problems,
      swallowing/chewing difficulties, excessive drooling, and communication
      impairments at age 5 years. RESULTS: a total of 1357 children born between 1980
      and 2001 were studied (781 males, 576 females; median age 5y 11mo, interquartile
      range 3-9y; unilateral spastic CP, n=447; bilateral spastic CP, n=496; other,
      n=112; Gross Motor Function Classification System [GMFCS] level: I, 181; II, 563;
      III, 123; IV, 82; IV, 276). Of those with 'early-onset' CP (n=1268), 36% had
      motor speech problems, 21% had swallowing/chewing difficulties, 22% had excessive
      drooling, and 42% had communication impairments (excluding articulation defects).
      All impairments were significantly related to poorer gross motor function and
      intellectual impairment. In addition, motor speech problems were related to
      clinical subtype; swallowing/chewing problems and communication impairments to
      early mortality; and communication impairments to the presence of seizures. Of
      those with CP in GMFCS levels IV to V, a significant proportion showed a decline
      in the rate of motor speech impairment (p=0.008) and excessive drooling (p=0.009)
      over time. INTERPRETATION: these impairments are common in children with CP and
      are associated with poorer gross motor function and intellectual impairment.

PMID- 20813021
TI  - Intervention for mixed receptive-expressive language impairment: a review.
AB  - Studies indicate that language impairment that cannot be accounted for by factors
      such as below-average non-verbal ability, hearing impairment, behaviour or
      emotional problems, or neurological impairments affects some 6% of school-age
      children. Language impairment with a receptive language component is more
      resistant to intervention than specific expressive or phonological delays, and
      carries a greater risk of comorbid behavioural difficulties as well as adverse
      outcomes for language development and academic progress. This paper considers
      underlying explanations that may account for receptive-expressive language
      impairment. It also reviews evidence for the effectiveness of intervention from
      theory and recent systematic reviews, trials, and speech and language therapy
      practice.

PMID- 20813022
TI  - Evaluation of three commercial ELISA kits for anticardiolipin and anti-beta2
      glycoprotein I antibodies in the laboratory diagnosis of the antiphospholipid
      syndrome.
AB  - INTRODUCTION: The laboratory criteria of the antiphospholipid syndrome (APS)
      include lupus anticoagulant (LAC), anticardiolipin antibodies (aCL) and anti
      beta2glycoprotein I antibodies (abeta2GPI) IgG or IgM. METHODS: We evaluated
      three commercial ELISAs for aCL and abeta2GPI IgG and IgM: Asserachrom(r)
      ('Stago'), Bio-Rad ('BR') and the BindazymeTM (the Binding Site, 'BS'). RESULTS:
      Results of all assays and of LAC were correlated with the clinical background
      (n=228). Sensitivity for Stago/BS/BR aCL IgG was 14%/15%/18%, for aCL IgM
      1%/5%/4%, for abeta2GPI IgG 9%/10%/17% and for abeta2GPI IgM 4%/4%/3%. The
      specificity for Stago/BS/BR for all assays ranged from 86% to 98%. The positive
      predictive value (PPV) for Stago/BS/BR aCL IgG was 46%/52%/40%, for aCL IgM
      8%/36%/19%, for abeta2GPI IgG 70%/67%/45% and for abeta2GPI IgM 23%/23%/20%.
      Combining LAC with aCL and abeta2GPI antibodies increased the sensitivity
      (Stago/BS/BR IgG: 26%/27%/31%, IgM: 22%/21%/26%) and PPV (Stago/BS/BR IgG:
      41%/46%/36%, IgM: 34%/40%/36%). Comparing the diagnostic power of the tests, only
      Stago/BS abeta2GPI IgG had a Chi-square P-value lower than 0.05. The combination
      of LAC and IgG ELISAs of BS resulted in the lowest P-value (0.098) compared to
      the other combinations. CONCLUSION: All evaluated ELISAs are a practical tool in
      the laboratory diagnosis of APS. The diagnostic performance shows slight
      differences between the ELISAs from the different manufacturers.

PMID- 20813023
TI  - Medium-term results of stapled transanal rectal resection (STARR) for obstructed
      defecation and symptomatic rectal-anal intussusception.
AB  - AIM: Stapled transanal rectal resection (STARR) is an increasingly accepted
      treatment for obstructed defaecation syndrome (ODS) associated with internal
      rectal prolapse (IRP) and rectocoele. The aim of this study is to evaluate the
      medium to long-term outcomes of STARR for ODS. METHOD: The intermediate-term
      results of STARR used over a 9-year period were reviewed from the analysis of a
      prospectively maintained database. Patients were followed for a median period of
      98 (95% CI 85-112, range 5-386) weeks. RESULTS: Three hundred and forty-four (234
      woman) patients of median age 54 (19-90) years underwent STARR over a 9-year
      period. Preoperative symptoms included pelvic pain (93%), incomplete evacuation
      (90%), urgency (74%), a sensation of obstruction (65%) and rectal digitation
      (27%). Thirteen had the solitary rectal ulcer syndrome. Of 326 patients with
      follow-up data, 249 (76%) were followed beyond 1 year and 149 (43%) beyond 2
      years. The ODS score improved [14.6 +/- 5.4 pre vs 1.6 +/- 3.1 post (P < 0.0001)]
      as did the faecal incontinence (FI) score [3.5 +/- 3.3 pre vs 0.4 +/- 1.3 post (P
      < 0.0001)]. Fifteen (4.3%) patients reported deterioration in FI, and 11 (3.2%)
      experienced new onset minor incontinence. Urgency was 72% at 8 weeks, 20% at 16
      weeks, 11.5% at 52 weeks and 5% at 1.5 years. None of the 29 patients followed
      beyond 4 years reported urgency. Urgency was unrelated to sex, age or
      preoperative ODS symptoms (Mantel-Cox log-rank). Recurrent symptoms of ODS
      occurred in 4.9%. Eighty-one per cent of patients were highly satisfied with
      STARR and would recommend or have it again. CONCLUSION: STARR was successful for
      the treatment of selected patients with ODS and IRP. Postoperative faecal urgency
      rapidly decreases with time. It is not possible to predict who will develop
      urgency.

PMID- 20813024
TI  - Comparison of the antimicrobial activity of Ulmo honey from Chile and Manuka
      honey against methicillin-resistant Staphylococcus aureus, Escherichia coli and
      Pseudomonas aeruginosa.
AB  - BACKGROUND: Honey has previously been shown to have wound healing and
      antimicrobial properties, but this is dependent on the type of honey,
      geographical location and flower from which the final product is derived. We
      tested the antimicrobial activity of a Chilean honey made by Apis mellifera
      (honeybee) originating from the Ulmo tree (Eucryphia cordifolia), against
      selected strains of bacteria. METHODS: Ulmo 90 honey was compared with manuka UMF
      25+ (Comvita) honey and a laboratory synthesised (artificial) honey. An agar well
      diffusion assay and a 96 well minimum inhibitory concentration (MIC)
      spectrophotometric-based assay were used to assess antimicrobial activity against
      five strains of methicillin-resistant Staphylococcus aureus (MRSA), Escherichia
      coli and Pseudomonas aeruginosa. RESULTS: Initial screening with the agar
      diffusion assay demonstrated that Ulmo 90 honey had greater antibacterial
      activity against all MRSA isolates tested than manuka honey and similar activity
      against E. coli and P. aeruginosa. The MIC assay, showed that a lower MIC was
      observed with Ulmo 90 honey (3.1% - 6.3% v/v) than with manuka honey (12.5% v/v)
      for all five MRSA isolates. For the E. coli and Pseudomonas strains equivalent
      MICs were observed (12.5% v/v). The MIC for artificial honey was 50% v/v. The
      minimum bactericidal concentration for all isolates tested for Ulmo 90 honey was
      identical to the MIC. Unlike manuka honey, Ulmo 90 honey activity is largely due
      to hydrogen peroxide production. CONCLUSIONS: Due to its high antimicrobial
      activity, Ulmo 90 may warrant further investigation as a possible alternative
      therapy for wound healing.

PMID- 20813025
TI  - Dangerous drug interactions leading to hemolytic uremic syndrome following lung
      transplantation.
AB  - BACKGROUND: To report our experience of a rather uncommon drug interaction,
      resulting in hemolytic uremic syndrome (HUS). METHODS: Two consecutive cases of
      hemolytic uremic syndrome were diagnosed in our service. In both patients the use
      of macrolides in patients taking Tacrolimus, resulted in high levels of
      Tacrolimus. RESULTS: The first patient was a 48 years old female with Bilateral
      emphysema. She underwent Single Sequential Lung Transplantation. She developed
      reperfusion injury requiring prolonged stay. Tacrolimus introduced (Day 51). The
      patient remained well up till 5 months later; Erythromycin commenced for chest
      infection. High Tacrolimus levels and a clinical diagnosis of HUS were made. She
      was treated with plasmapheresis successfully. The second case was a 57 years old
      female with Emphysema & A1 Antithrypsin deficiency. She underwent Right Single
      Lung Transplantation. A2 rejection with mild Obliterative Bronchiolitis diagnosed
      1 year later and she switched to Tacrolimus. She was admitted to her local
      Hospital two and a half years later with right middle lobe consolidation. The
      patient commenced on amoxicillin and clarithromycin. Worsening renal indices,
      high Tacrolimus levels, hemolytic anemia & low Platelets were detected. HUS
      diagnosed & treated with plasmapheresis. CONCLUSIONS: There are 21 cases of HUS
      following lung transplantation in the literature that may have been induced by
      high tacrolimus levels. Macrolides in patients taking Cyclosporin or Tacrolimus
      lead to high levels. Mechanism of action could be glomeruloconstrictor effect
      with reduced GFR increased production of Endothelin-1 and increased Platelet
      aggregation.

PMID- 20813026
TI  - Data and programming code from the studies on the learning curve for radical
      prostatectomy.
AB  - Our group analyzed a multi-institutional data set to address the question of how
      the outcomes of surgery for prostate cancer are affected by surgeon-specific
      factors. The cohort consists of 9076 patients treated by open radical
      prostatectomy at one of four US academic institutions 1987 - 2003. The primary
      analyses focused on 7765 patients without neoadjuvant therapy. The most well
      known finding is that of a surgical "learning curve", with rates of prostate
      cancer cure strongly dependent on surgeon experience. In this "data note", we
      provide the raw data set, as well as well-annotated programming code for the main
      analyses. Data include markers of cancer severity (stage, grade and prostate
      specific antigen level), cancer outcome, and surgeon variables such as training
      and experience.

PMID- 20813027
TI  - A call for BMC Research Notes contributions promoting best practice in data
      standardization, sharing and publication.
AB  - BMC Research Notes aims to ensure that data files underlying published articles
      are made available in standard, reusable formats, and the journal is calling for
      contributions from the scientific community to achieve this goal. Educational
      Data Notes included in this special series should describe a domain-specific data
      standard and provide an example data set with the article, or a link to data that
      are permanently hosted elsewhere. The contributions should also provide some
      evidence of the data standard's application and preparation guidance that could
      be used by others wishing to conduct similar experiments. The journal is also
      keen to receive contributions on broader aspects of scientific data sharing,
      archiving, and open data.

PMID- 20813028
TI  - An algorithm to discover gene signatures with predictive potential.
AB  - BACKGROUND: The advent of global gene expression profiling has generated
      unprecedented insight into our molecular understanding of cancer, including
      breast cancer. For example, human breast cancer patients display significant
      diversity in terms of their survival, recurrence, metastasis as well as response
      to treatment. These patient outcomes can be predicted by the transcriptional
      programs of their individual breast tumors. Predictive gene signatures allow us
      to correctly classify human breast tumors into various risk groups as well as to
      more accurately target therapy to ensure more durable cancer treatment. RESULTS:
      Here we present a novel algorithm to generate gene signatures with predictive
      potential. The method first classifies the expression intensity for each gene as
      determined by global gene expression profiling as low, average or high. The
      matrix containing the classified data for each gene is then used to score the
      expression of each gene based its individual ability to predict the patient
      characteristic of interest. Finally, all examined genes are ranked based on their
      predictive ability and the most highly ranked genes are included in the master
      gene signature, which is then ready for use as a predictor. This method was used
      to accurately predict the survival outcomes in a cohort of human breast cancer
      patients. CONCLUSIONS: We confirmed the capacity of our algorithm to generate
      gene signatures with bona fide predictive ability. The simplicity of our
      algorithm will enable biological researchers to quickly generate valuable gene
      signatures without specialized software or extensive bioinformatics training.

PMID- 20813029
TI  - Sexual behaviour of men that consulted in medical outpatient clinics in Western
      Switzerland from 2005-2006: risk levels unknown to doctors?
AB  - BACKGROUND: To determine male outpatient attenders' sexual behaviours,
      expectations and experience of talking about their sexuality and sexual health
      needs with a doctor. METHODS: A survey was conducted among all male patients aged
      18-70, recruited from the two main medical outpatient clinics in Lausanne,
      Switzerland, in 2005-2006. The anonymous self-administered questionnaire included
      questions on sexual behaviour, HIV/STI information needs, expectations and
      experiences regarding discussion of sexual matters with a doctor. RESULTS: The
      response rate was 53.0% (N = 1452). The mean age was 37.7 years. Overall, 13.4%
      of patients were defined as at STI risk--i.e. having not consistently used
      condoms with casual partners in the last 6 months, or with a paid partner during
      the last intercourse--regarding their sexual behaviour in the last year. 90.9%
      would have liked their physician to ask them questions concerning their sexual
      life; only 61.4% had ever had such a discussion. The multivariate analysis showed
      that patients at risk tended to have the following characteristics: recruited
      from the HIV testing clinic, lived alone, declared no religion, had a low level
      of education, felt uninformed about HIV/AIDS, were younger, had had concurrent
      sexual partners in the last 12 months. However they were not more likely to have
      discussed sexual matters with their doctor than patients not at risk. CONCLUSION:
      Recording the sexual history and advice on the prevention of the risks of STI
      should become routine practice for primary health care doctors.

PMID- 20813030
TI  - Expression of immune-response genes in lepidopteran host is suppressed by venom
      from an endoparasitoid, Pteromalus puparum.
AB  - BACKGROUND: The relationships between parasitoids and their insect hosts have
      attracted attention at two levels. First, the basic biology of host-parasitoid
      interactions is of fundamental interest. Second, parasitoids are widely used as
      biological control agents in sustainable agricultural programs. Females of the
      gregarious endoparasitoid Pteromalus puparum (Hymenoptera: Pteromalidae) inject
      venom along with eggs into their hosts. P. puparum does not inject polydnaviruses
      during oviposition. For this reason, P. puparum and its pupal host, the small
      white butterfly Pieris rapae (Lepidoptera: Pieridae), comprise an excellent model
      system for studying the influence of an endoparasitoid venom on the biology of
      the pupal host. P. puparum venom suppresses the immunity of its host, although
      the suppressive mechanisms are not fully understood. In this study, we tested our
      hypothesis that P. puparum venom influences host gene expression in the two main
      immunity-conferring tissues, hemocytes and fat body. RESULTS: At 1 h post-venom
      injection, we recorded significant decreases in transcript levels of 217 EST
      clones (revealing 113 genes identified in silico, including 62 unknown contigs)
      derived from forward subtractive libraries of host hemocytes and in transcript
      levels of 288 EST clones (221 genes identified in silico, including 123 unknown
      contigs) from libraries of host fat body. These genes are related to insect
      immune response, cytoskeleton, cell cycle and apoptosis, metabolism, transport,
      stress response and transcriptional and translational regulation. We verified the
      reliability of the suppression subtractive hybridization (SSH) data with semi
      quantitative RT-PCR analysis of a set of randomly selected genes. This analysis
      showed that most of the selected genes were down-regulated after venom injection.
      CONCLUSIONS: Our findings support our hypothesis that P. puparum venom influences
      gene expression in host hemocytes and fat body. Specifically, the venom
      treatments led to reductions in expression of a large number of genes. Many of
      the down-regulated genes act in immunity, although others act in non-immune areas
      of host biology. We conclude that the actions of venom on host gene expression
      influence immunity as well as other aspects of host biology in ways that benefit
      the development and emergence of the next generation of parasitoids.

PMID- 20813031
TI  - Epidemiological and economic burden of metabolic syndrome and its consequences in
      patients with hypertension in Germany, Spain and Italy; a prevalence-based model.
AB  - BACKGROUND: The presence of metabolic syndrome in patients with hypertension
      significantly increases the risk of cardiovascular disease, type 2 diabetes and
      mortality. Our aim is to estimate the epidemiological and economic burden to the
      health service of metabolic syndrome in patients with hypertension in three
      European countries in 2008 and 2020. METHODS: An age, sex and risk group
      structured prevalence based cost of illness model was developed using the United
      States Adult Treatment Panel III of the National Cholesterol Education Program
      criteria to define metabolic syndrome. Data sources included published
      information and public use databases on disease prevalence, incidence of
      cardiovascular events, prevalence of type 2 diabetes, treatment patterns and cost
      of management in Germany, Spain and Italy. RESULTS: The prevalence of
      hypertension with metabolic syndrome in the general population of Germany, Spain
      and Italy was 36%, 11% and 10% respectively. In subjects with hypertension 61%,
      22% and 21% also had metabolic syndrome. Incident cardiovascular events and
      attributable mortality were around two fold higher in subjects with metabolic
      syndrome and prevalence of type 2 diabetes was around six-fold higher. The
      economic burden to the health service of metabolic syndrome in patients with
      hypertension was been estimated at ?24,427, ?1,900 and ?4,877 million in Germany,
      Spain and Italy and forecast to rise by 59%, 179% and 157% respectively by 2020.
      The largest components of costs included the management of prevalent type 2
      diabetes and incident cardiovascular events. Mean annual costs per hypertensive
      patient were around three-fold higher in subjects with metabolic syndrome
      compared to those without and rose incrementally with the additional number of
      metabolic syndrome components present. CONCLUSION: The presence of metabolic
      syndrome in patients with hypertension significantly inflates economic burden and
      costs are likely to increase in the future due to an aging population and an
      increase in the prevalence of components of metabolic syndrome.

PMID- 20813032
TI  - Mobilizing diversity: transposable element insertions in genetic variation and
      disease.
AB  - Transposable elements (TEs) comprise a large fraction of mammalian genomes. A
      number of these elements are actively jumping in our genomes today. As a
      consequence, these insertions provide a source of genetic variation and, in rare
      cases, these events cause mutations that lead to disease. Yet, the extent to
      which these elements impact their host genomes is not completely understood. This
      review will summarize our current understanding of the mechanisms underlying
      transposon regulation and the contribution of TE insertions to genetic diversity
      in the germline and in somatic cells. Finally, traditional methods and emerging
      technologies for identifying transposon insertions will be considered.

PMID- 20813033
TI  - Island biology and morphological divergence of the Skyros wall lizard Podarcis
      gaigeae: a combined role for local selection and genetic drift on color morph
      frequency divergence?
AB  - BACKGROUND: Patterns of spatial variation in discrete phenotypic traits can be
      used to draw inferences about the adaptive significance of traits and
      evolutionary processes, especially when compared to patterns of neutral genetic
      variation. Population divergence in adaptive traits such as color morphs can be
      influenced by both local ecology and stochastic factors such as genetic drift or
      founder events. Here, we use quantitative color measurements of males and females
      of Skyros wall lizard, Podarcis gaigeae, to demonstrate that this species is
      polymorphic with respect to throat color, and the morphs form discrete phenotypic
      clusters with limited overlap between categories. We use divergence in throat
      color morph frequencies and compare that to neutral genetic variation to infer
      the evolutionary processes acting on islet- and mainland populations. RESULTS:
      Geographically close islet- and mainland populations of the Skyros wall lizard
      exhibit strong divergence in throat color morph frequencies. Population variation
      in throat color morph frequencies between islets was higher than that between
      mainland populations, and the effective population sizes on the islets were small
      (Ne:s < 100). Population divergence (FST) for throat color morph frequencies fell
      within the neutral FST-distribution estimated from microsatellite markers, and
      genetic drift could thus not be rejected as an explanation for the pattern.
      Moreover, for both comparisons among mainland-mainland population pairs and
      between mainland-islet population pairs, morph frequency divergence was
      significantly correlated with neutral divergence, further pointing to some role
      for genetic drift in divergence also at the phenotypic level of throat color
      morphs. CONCLUSIONS: Genetic drift could not be rejected as an explanation for
      the pattern of population divergence in morph frequencies. In spite of an
      expected stabilising selection, throat color frequencies diverged in the islet
      populations. These results suggest that there is an interaction between selection
      and genetic drift causing divergence even at a phenotypic level in these small,
      subdivided populations.

PMID- 20813034
TI  - Mosquito nets in a rural area of Western Kenya: ownership, use and quality.
AB  - BACKGROUND: Insecticide-treated nets (ITNs) are regarded as one of the most
      effective strategies to prevent malaria in Africa. This study analyses the use
      and quality of nets owned by households in an area of high net coverage. METHODS:
      A structured questionnaire on ownership and use of nets was administered to the
      households of individuals sampled from a local health centre in south Kisii
      district, Kenya. A physical inspection of all the nets in the households was done
      and their conditions recorded on spot check forms designed for that purpose.
      RESULTS: Of the 670 households surveyed, 95% owned at least one net. Only 59% of
      household residents slept under a net during the night prior to the survey. 77%
      of those who slept under a net used an insecticide-treated net (ITN) or long
      lasting insecticide-treated nets (LLIN). Out of 1,627 nets in the survey
      households, 40% were deemed to be of poor quality because of holes. Compared to
      other age groups, children aged 5-14 years were most likely to have slept under
      nets of poor quality (odds ratio 1.41; p = 0.007). CONCLUSIONS: Although net
      ownership was high following increased delivery of ITNs, continuous promotion of
      effective maintenance and routine use is needed and efforts to replace damaged
      nets must be implemented.

PMID- 20813035
TI  - Phenotypic and molecular characterization of the claudin-low intrinsic subtype of
      breast cancer.
AB  - INTRODUCTION: In breast cancer, gene expression analyses have defined five tumor
      subtypes (luminal A, luminal B, HER2-enriched, basal-like and claudin-low), each
      of which has unique biologic and prognostic features. Here, we comprehensively
      characterize the recently identified claudin-low tumor subtype. METHODS: The
      clinical, pathological and biological features of claudin-low tumors were
      compared to the other tumor subtypes using an updated human tumor database and
      multiple independent data sets. These main features of claudin-low tumors were
      also evaluated in a panel of breast cancer cell lines and genetically engineered
      mouse models. RESULTS: Claudin-low tumors are characterized by the low to absent
      expression of luminal differentiation markers, high enrichment for epithelial-to
      mesenchymal transition markers, immune response genes and cancer stem cell-like
      features. Clinically, the majority of claudin-low tumors are poor prognosis
      estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and
      epidermal growth factor receptor 2 (HER2)-negative (triple negative) invasive
      ductal carcinomas with a high frequency of metaplastic and medullary
      differentiation. They also have a response rate to standard preoperative
      chemotherapy that is intermediate between that of basal-like and luminal tumors.
      Interestingly, we show that a group of highly utilized breast cancer cell lines,
      and several genetically engineered mouse models, express the claudin-low
      phenotype. Finally, we confirm that a prognostically relevant differentiation
      hierarchy exists across all breast cancers in which the claudin-low subtype most
      closely resembles the mammary epithelial stem cell. CONCLUSIONS: These results
      should help to improve our understanding of the biologic heterogeneity of breast
      cancer and provide tools for the further evaluation of the unique biology of
      claudin-low tumors and cell lines.

PMID- 20813036
TI  - Mental health priorities in Vietnam: a mixed-methods analysis.
AB  - BACKGROUND: The Mental Health Country Profile is a tool that was generated by the
      International Mental Health Policy and Services Project to inform policy makers,
      professionals and other key stakeholders about important issues which need to be
      considered in mental health policy development. The Mental Health Country Profile
      contains four domains, which include the mental health context, resources,
      provision and outcomes. We have aimed to generate a Mental Health Country Profile
      for Vietnam, in order to highlight the strengths and weaknesses of the Vietnamese
      mental health situation, in order to inform future reform efforts and decision
      making. METHODS: This study used snowball sampling to identify informants for
      generating a Mental Health Country Profile for Vietnam, and the data gathering
      was done through semi-structured interviews and collection of relevant reports
      and documents. The material from the interviews and documents was analysed
      according to qualitative content analysis. RESULTS: Marked strengths of the
      Vietnam mental health system are the aims to move toward community management and
      detection of mental illness, and the active involvement of several multilateral
      organizations and NGOs. However, there are a number of shortages still found,
      including the lack of treatment interventions apart from medications, the high
      proportion of treatments to be paid out-of-pocket, prominence of large tertiary
      psychiatric hospitals, and a lack of preventative measures or mental health
      information to the public. CONCLUSIONS: At the end of this decade, mental health
      care in Vietnam is still characterised by unclear policy and poor critical mass
      especially within the governmental sector. This initial attempt to map the mental
      health situation of Vietnam suffers from a number of limitations and should be
      seen as a first step towards a comprehensive profile.

PMID- 20813037
TI  - Cyst formation in the PKD2 (1-703) transgenic rat precedes deregulation of
      proliferation-related pathways.
AB  - BACKGROUND: Polycystic Kidney Disease is characterized by the formation of large
      fluid-filled cysts that eventually destroy the renal parenchyma leading to end
      stage renal failure. Although remarkable progress has been made in understanding
      the pathologic mechanism of the disease, the precise orchestration of the early
      events leading to cyst formation is still unclear. Abnormal cellular
      proliferation was traditionally considered to be one of the primary
      irregularities leading to cyst initiation and growth. Consequently, many
      therapeutic interventions have focused on targeting this abnormal proliferation,
      and some have even progressed to clinical trials. However, the role of
      proliferation in cyst development was primarily examined at stages where cysts
      are already visible in the kidneys and therefore at later stages of disease
      development. METHODS: In this study we focused on the cystic phenotype since
      birth in an attempt to clarify the temporal contribution of cellular
      proliferation in cyst development. Using a PKD2 transgenic rat model (PKD2 (1
      703)) of different ages (0-60 days after birth) we performed gene expression
      profiling and phenotype analysis by measuring various kidney parameters. RESULTS:
      Phenotype analysis demonstrated that renal cysts appear immediately after birth
      in the PKD2 transgenic rat model (PKD2 (1-703)). On the other hand, abnormal
      proliferation occurs at later stages of the disease as identified by gene
      expression profiling. Interestingly, other pathways appear to be deregulated at
      early stages of the disease in this PKD model. Specifically, gene expression
      analysis demonstrated that at day 0 the RAS system is involved. This is altered
      at day 6, when Wnt signaling and focal adhesion pathways are affected. However,
      at and after 24 days, proliferation, apoptosis, altered ECM signaling and many
      other factors become involved. CONCLUSIONS: Our data suggest that cystogenesis
      precedes deregulation of proliferation-related pathways, suggesting that
      proliferation abnormalities may contribute in cyst growth rather than cyst
      formation.

PMID- 20813038
TI  - No evidence of altered alveolar macrophage polarization, but reduced expression
      of TLR2, in bronchoalveolar lavage cells in sarcoidosis.
AB  - BACKGROUND: Sarcoidosis is a granulomatous inflammatory disease, possibly of
      infectious aetiology. We aimed to investigate whether the degree of functional
      polarization of alveolar macrophages (AMs), or Toll-like receptor (TLR)
      expression, is associated with sarcoidosis or with distinct clinical
      manifestations of this disease. METHODS: Total BAL cells (cultured four or 24 h
      in medium, or stimulated 24 h with LPS) from 14 patients and six healthy
      subjects, sorted AMs from 22 patients (Lofgren's syndrome n = 11) and 11 healthy
      subjects, and sorted CD4+ T cells from 26 patients (Lofgren's syndrome n = 13)
      and seven healthy subjects, were included. Using real-time PCR, the relative gene
      expression of IL-10, IL-12p35, IL-12p40, IL-23p19, CCR2, CCR7, iNOS, CXCL10,
      CXCL11, CXCL16, CCL18, CCL20, CD80, and CD86, and innate immune receptors TLR2,
      TLR4, and TLR9, was quantified in sorted AMs, and for selected genes in total BAL
      cells, while IL-17A was quantified in T cells. RESULTS: We did not find evidence
      of a difference with regard to alveolar macrophage M1/M2 polarization between
      sarcoidosis patients and healthy controls. TLR2 gene expression was significantly
      lower in sorted AMs from patients, particular in Lofgren's patients. CCL18 gene
      expression in AMs was significantly higher in patients compared to controls.
      Additionally, the IL-17A expression was lower in Lofgren's patients' CD4+ T
      cells. CONCLUSIONS: Overall, there was no evidence for alveolar macrophage
      polarization in sarcoidosis. However, there was a reduced TLR2 mRNA expression in
      patients with Lofgren's syndrome, which may be of relevance for macrophage
      interactions with a postulated sarcoidosis pathogen, and for the characteristics
      of the ensuing T cell response.

PMID- 20813039
TI  - The chicken miR-150 targets the avian orthologue of the functional zebrafish MYB
      3'UTR target site.
AB  - BACKGROUND: The c-myb proto-oncogene is the founding member of a family of
      transcription factors involved principally in haematopoiesis, in diverse
      organisms, from zebrafish to mammals. Its deregulation has been implicated in
      human leukaemogenesis and other cancers. The expression of c-myb is tightly
      regulated by post-transcriptional mechanisms involving microRNAs. MicroRNAs are
      small, highly conserved non-coding RNAs that inhibit translation and decrease
      mRNA stability by binding to regulatory motifs mostly located in the 3'UTR of
      target mRNAs conserved throughout evolution. MYB is an evolutionarily conserved
      miR-150 target experimentally validated in mice, humans and zebrafish. However,
      the functional miR-150 sites of humans and mice are orthologous, whereas that of
      zebrafish is different. RESULTS: We identified the avian mature miRNA-150-5P,
      Gallus gallus gga-miR-150 from chicken leukocyte small-RNA libraries and showed
      that, as expected, the gga-miR-150 sequence was highly conserved, including the
      seed region sequence present in the other miR-150 sequences listed in miRBase.
      Reporter assays showed that gga-miR-150 acted on the avian MYB 3'UTR and
      identified the avian MYB target site involved in gga-miR-150 binding. A
      comparative in silico analysis of the miR-150 target sites of MYB 3'UTRs from
      different species led to the identification of a single set of putative target
      sites in amphibians and zebrafish, whereas two sets of putative target sites were
      identified in chicken and mammals. However, only the target site present in the
      chicken MYB 3'UTR that was identical to that in zebrafish was functional, despite
      the additional presence of mammalian target sites in chicken. This specific miR
      150 site usage was not cell-type specific and persisted when the chicken c-myb
      3'UTR was used in the cell system to identify mammalian target sites, showing
      that this miR-150 target site usage was intrinsic to the chicken c-myb 3'UTR.
      CONCLUSION: Our study of the avian MYB/gga-miR-150 interaction shows a
      conservation of miR-150 target site functionality between chicken and zebrafish
      that does not extend to mammals.

PMID- 20813040
TI  - Quadricuspid aortic valve by using intraoperative transesophageal
      echocardiography.
AB  - Quadricuspid aortic valve is a rare congenital malformation of the aortic valve.
      Its diagnosis is often missed even with the use of transthoracic echocardiogram.
      Many of these patients progress to aortic incompetence later in life, hence
      requiring surgical intervention. In the case described in this report, a 61-year
      old woman is presented with the features of congestive heart failure. The
      preoperative transthoracic echocardiogram disclosed a moderate to severe aortic
      valve insufficiency but failed to reveal the quadricuspid aortic value anomaly.
      This case underscores the important role of three-dimensional transesophageal
      echocardiography for the diagnosis of quadricuspid aortic valve.

PMID- 20813041
TI  - Fragmentation of the large subunit ribosomal RNA gene in oyster mitochondrial
      genomes.
AB  - BACKGROUND: Discontinuous genes have been observed in bacteria, archaea, and
      eukaryotic nuclei, mitochondria and chloroplasts. Gene discontinuity occurs in
      multiple forms: the two most frequent forms result from introns that are spliced
      out of the RNA and the resulting exons are spliced together to form a single
      transcript, and fragmented gene transcripts that are not covalently attached post
      transcriptionally. Within the past few years, fragmented ribosomal RNA (rRNA)
      genes have been discovered in bilateral metazoan mitochondria, all within a group
      of related oysters. RESULTS: In this study, we have characterized this
      fragmentation with comparative analysis and experimentation. We present secondary
      structures, modeled using comparative sequence analysis of the discontinuous
      mitochondrial large subunit rRNA genes of the cupped oysters C. virginica, C.
      gigas, and C. hongkongensis. Comparative structure models for the large subunit
      rRNA in each of the three oyster species are generally similar to those for other
      bilateral metazoans. We also used RT-PCR and analyzed ESTs to determine if the
      two fragmented LSU rRNAs are spliced together. The two segments are transcribed
      separately, and not spliced together although they still form functional rRNAs
      and ribosomes. CONCLUSIONS: Although many examples of discontinuous ribosomal
      genes have been documented in bacteria and archaea, as well as the nuclei,
      chloroplasts, and mitochondria of eukaryotes, oysters are some of the first
      characterized examples of fragmented bilateral animal mitochondrial rRNA genes.
      The secondary structures of the oyster LSU rRNA fragments have been predicted on
      the basis of previous comparative metazoan mitochondrial LSU rRNA structure
      models.

PMID- 20813042
TI  - Chk1 suppressed cell death.
AB  - The role of Chk1 in the cellular response to DNA replication stress is well
      established. However recent work indicates a novel role for Chk1 in the
      suppression of apoptosis following the disruption of DNA replication or DNA
      damage. This review will consider these findings in the context of known pathways
      of Chk1 signalling and potential applications of therapies that target Chk1.

PMID- 20813043
TI  - Distinct patterns of mitochondrial genome diversity in bonobos (Pan paniscus) and
      humans.
AB  - BACKGROUND: We have analyzed the complete mitochondrial genomes of 22 Pan
      paniscus (bonobo, pygmy chimpanzee) individuals to assess the detailed
      mitochondrial DNA (mtDNA) phylogeny of this close relative of Homo sapiens.
      RESULTS: We identified three major clades among bonobos that separated
      approximately 540,000 years ago, as suggested by Bayesian analysis. Incidentally,
      we discovered that the current reference sequence for bonobo likely is a hybrid
      of the mitochondrial genomes of two distant individuals. When comparing spectra
      of polymorphic mtDNA sites in bonobos and humans, we observed two major
      differences: (i) Of all 31 bonobo mtDNA homoplasies, i.e. nucleotide changes that
      occurred independently on separate branches of the phylogenetic tree, 13 were not
      homoplasic in humans. This indicates that at least a part of the unstable sites
      of the mitochondrial genome is species-specific and difficult to be explained on
      the basis of a mutational hotspot concept. (ii) A comparison of the ratios of non
      synonymous to synonymous changes (dN/dS) among polymorphic positions in bonobos
      and in 4902 Homo sapiens mitochondrial genomes revealed a remarkable difference
      in the strength of purifying selection in the mitochondrial genes of the F0F1
      ATPase complex. While in bonobos this complex showed a similar low value as
      complexes I and IV, human haplogroups displayed 2.2 to 7.6 times increased dN/dS
      ratios when compared to bonobos. CONCLUSIONS: Some variants of mitochondrially
      encoded subunits of the ATPase complex in humans very likely decrease the
      efficiency of energy conversion leading to production of extra heat. Thus, we
      hypothesize that the species-specific release of evolutionary constraints for the
      mitochondrial genes of the proton-translocating ATPase is a consequence of
      altered heat homeostasis in modern humans.

PMID- 20813044
TI  - Storytelling as a communication tool for health consumers: development of an
      intervention for parents of children with croup. Stories to communicate health
      information.
AB  - BACKGROUND: Stories may be an effective tool to communicate with and influence
      patients because of their ability to engage the reader. The objective of this
      paper is to describe the development of a story-based intervention for delivery
      of health evidence to parents of children with croup for use in a randomized
      controlled trial. METHODS: A creative writer interviewed parents of children with
      croup presenting to the pediatric emergency department (ED) and drafted stories.
      We revised the stories based on written participant feedback and edited the
      stories to incorporate research evidence and health information. An illustrator
      and graphic designer developed story booklets which were evaluated through focus
      groups. RESULTS: Ten participants provided feedback on the five stories drafted
      by the creative writer. Participants liked the concept but found the writing
      overly sophisticated and wanted more character development and more
      medical/health information. Participants highlighted specific story content that
      they liked and disliked. The revised stories were evaluated through focus groups
      involving eight individuals. Feedback was generally positive; one participant
      questioned the associated costs. Participants liked the graphics and layout; felt
      that they could identify with the stories; and felt that it was easier to get
      information compared to a standard medical information sheet. Participants
      provided feedback on the story content, errors and inconsistencies, and
      preferences of writing style and booklet format. Feedback on how to package the
      stories was provided by attendees at a national meeting of pediatric emergency
      researchers. CONCLUSIONS: Several challenges arose during the development of the
      stories including: staying true to the story versus being evidence based;
      addressing the use of the internet by consumers as a source of health
      information; balancing the need to be comprehensive and widely applicable while
      being succinct; considerations such as story length, reading level, narrative
      mode, representation of different demographics and illness experiences, graphics
      and layout. The process was greatly informed by feedback from the end-user group.
      This allowed us to shape our products to ensure accuracy, credibility, and
      relevance. Our experience is valuable for further work in the area of stories and
      narratives, as well as more broadly for identifying and developing communication
      strategies for healthcare consumers.

PMID- 20813045
TI  - Genome3D: a viewer-model framework for integrating and visualizing multi-scale
      epigenomic information within a three-dimensional genome.
AB  - BACKGROUND: New technologies are enabling the measurement of many types of
      genomic and epigenomic information at scales ranging from the atomic to nuclear.
      Much of this new data is increasingly structural in nature, and is often
      difficult to coordinate with other data sets. There is a legitimate need for
      integrating and visualizing these disparate data sets to reveal structural
      relationships not apparent when looking at these data in isolation. RESULTS: We
      have applied object-oriented technology to develop a downloadable visualization
      tool, Genome3D, for integrating and displaying epigenomic data within a
      prescribed three-dimensional physical model of the human genome. In order to
      integrate and visualize large volume of data, novel statistical and mathematical
      approaches have been developed to reduce the size of the data. To our knowledge,
      this is the first such tool developed that can visualize human genome in three
      dimension. We describe here the major features of Genome3D and discuss our multi
      scale data framework using a representative basic physical model. We then
      demonstrate many of the issues and benefits of multi-resolution data integration.
      CONCLUSIONS: Genome3D is a software visualization tool that explores a wide range
      of structural genomic and epigenetic data. Data from various sources of differing
      scales can be integrated within a hierarchical framework that is easily adapted
      to new developments concerning the structure of the physical genome. In addition,
      our tool has a simple annotation mechanism to incorporate non-structural
      information. Genome3D is unique is its ability to manipulate large amounts of
      multi-resolution data from diverse sources to uncover complex and new structural
      relationships within the genome.

PMID- 20813046
TI  - MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma.
AB  - BACKGROUND: MiR-221 and miR-222 (miR-221/222) are frequently up-regulated in
      various types of human malignancy including glioblastoma. Recent studies have
      reported that miR-221/222 regulate cell growth and cell cycle progression by
      targeting p27 and p57. However the underlying mechanism involved in cell survival
      modulation of miR-221/222 remains elusive. RESULTS: Here we showed that miR
      221/222 inhibited cell apoptosis by targeting pro-apoptotic gene PUMA in human
      glioma cells. Enforced expression of miR-22/222 induced cell survival whereas
      knockdown of miR-221/222 rendered cells to apoptosis. Further, miR-221/222
      reduced PUMA protein levels by targeting PUMA-3'UTR. Introducing PUMA cDNA
      without 3'UTR abrogated miR-221/222-induced cell survival. Notably, knockdown of
      miR-221/222 induces PUMA expression and cell apoptosis and considerably decreases
      tumor growth in xenograft model. Finally, there was an inverse relationship
      between PUMA and miR-221/222 expression in glioma tissues. CONCLUSION: To our
      knowledge, these data indicate for the first time that miR-221/222 directly
      regulate apoptosis by targeting PUMA in glioblastoma and that miR-221/222 could
      be potential therapeutic targets for glioblastoma intervention.

PMID- 20813047
TI  - Gene expression following induction of regeneration in Drosophila wing imaginal
      discs. Expression profile of regenerating wing discs.
AB  - BACKGROUND: Regeneration is the ability of an organism to rebuild a body part
      that has been damaged or amputated, and can be studied at the molecular level
      using model organisms. Drosophila imaginal discs, which are the larval primordia
      of adult cuticular structures, are capable of undergoing regenerative growth
      after transplantation and in vivo culture into the adult abdomen. RESULTS: Using
      expression profile analyses, we studied the regenerative behaviour of wing discs
      at 0, 24 and 72 hours after fragmentation and implantation into adult females.
      Based on expression level, we generated a catalogue of genes with putative role
      in wing disc regeneration, identifying four classes: 1) genes with differential
      expression within the first 24 hours; 2) genes with differential expression
      between 24 and 72 hours; 3) genes that changed significantly in expression levels
      between the two time periods; 4) genes with a sustained increase or decrease in
      their expression levels throughout regeneration. Among these genes, we identified
      members of the JNK and Notch signalling pathways and chromatin regulators.
      Through computational analysis, we recognized putative binding sites for
      transcription factors downstream of these pathways that are conserved in multiple
      Drosophilids, indicating a potential relationship between members of the
      different gene classes. Experimental data from genetic mutants provide evidence
      of a requirement of selected genes in wing disc regeneration. CONCLUSIONS: We
      have been able to distinguish various classes of genes involved in early and late
      steps of the regeneration process. Our data suggests the integration of
      signalling pathways in the promoters of regulated genes.

PMID- 20813048
TI  - p21Waf1 expression is regulated by nuclear intermediate filament vimentin in
      neuroblastoma.
AB  - BACKGROUND: Human neuroblastoma (NB) cell lines may present with either one of
      the so-called S-and N-subtypes. We have previously reported a strong correlation
      between protein expression levels of vimentin, an S-subtype marker, and the
      p21Waf1 cyclin-dependent kinase inhibitor. We here investigated whether this
      correlation extend to the mRNA level in NB cell lines as well as in patients'
      tumors. We also further explored the relationship between expression of vimentin
      and p21, by asking whether vimentin could regulate p21 expression. METHODS:
      Vimentin and p21 mRNA levels in NB cell lines as well as in patients' tumors (n =
      77) were quantified using Q-PCR. Q-PCR data obtained from tumors of high risk NB
      patients (n = 40) were analyzed in relation with the overall survival using the
      Log-rank Kaplan-Meier estimation. siRNA-mediated depletion or overexpression of
      vimentin in highly or low expressing vimentin cell lines, respectively, followed
      by protein expression and promoter activation assays were used to assess the role
      of vimentin in modulating p21 expression. RESULTS: We extend the significant
      correlation between vimentin and p21 expression to the mRNA level in NB cell
      lines as well as in patients' tumors. Overall survival analysis from Q-PCR data
      obtained from tumors of high risk patients suggests that lower levels of p21
      expression could be associated with a poorer outcome. Our data additionally
      indicate that the correlation observed between p21 and vimentin expression levels
      results from p21 transcriptional activity being regulated by vimentin. Indeed,
      downregulating vimentin resulted in a significant decrease in p21 mRNA and
      protein expression as well as in p21 promoter activity. Conversely,
      overexpressing vimentin triggered an increase in p21 promoter activity in cells
      with a nuclear expression of vimentin. CONCLUSION: Our results suggest that p21
      mRNA tumor expression level could represent a refined prognostic factor for high
      risk NB patients. Our data also show that vimentin regulates p21 transcription;
      this is the first demonstration of a gene regulating function for this type III
      intermediate filament.

PMID- 20813049
TI  - Identification of tumor-associated cassette exons in human cancer through EST
      based computational prediction and experimental validation.
AB  - BACKGROUND: Many evidences report that alternative splicing, the mechanism which
      produces mRNAs and proteins with different structures and functions from the same
      gene, is altered in cancer cells. Thus, the identification and characterization
      of cancer-specific splice variants may give large impulse to the discovery of
      novel diagnostic and prognostic tumour biomarkers, as well as of new targets for
      more selective and effective therapies. RESULTS: We present here a genome-wide
      analysis of the alternative splicing pattern of human genes through a
      computational analysis of normal and cancer-specific ESTs from seventeen
      anatomical groups, using data available in AspicDB, a database resource for the
      analysis of alternative splicing in human. By using a statistical methodology,
      normal and cancer-specific genes, splice sites and cassette exons were predicted
      in silico. The condition association of some of the novel normal/tumoral cassette
      exons was experimentally verified by RT-qPCR assays in the same anatomical system
      where they were predicted. Remarkably, the presence in vivo of the predicted
      alternative transcripts, specific for the nervous system, was confirmed in
      patients affected by glioblastoma. CONCLUSION: This study presents a novel
      computational methodology for the identification of tumor-associated transcript
      variants to be used as cancer molecular biomarkers, provides its experimental
      validation, and reports specific biomarkers for glioblastoma.

PMID- 20813050
TI  - Automatic detection of anchor points for multiple sequence alignment.
AB  - BACKGROUND: determining beforehand specific positions to align (anchor points)
      has proved valuable for the accuracy of automated multiple sequence alignment
      (MSA) software. This feature can be used manually to include biological
      expertise, or automatically, usually by pairwise similarity searches. Multiple
      local similarities are be expected to be more adequate, as more biologically
      relevant. However, even good multiple local similarities can prove incompatible
      with the ordering of an alignment. RESULTS: we use a recently developed algorithm
      to detect multiple local similarities, which returns subsets of positions in the
      sequences sharing similar contexts of appearence. In this paper, we describe
      first how to get, with the help of this method, subsets of positions that could
      form partial columns in an alignment. We introduce next a graph-theoretic
      algorithm to detect (and remove) positions in the partial columns that are
      inconsistent with a multiple alignment. Partial columns can be used, for the time
      being, as guide only by a few MSA programs: ClustalW 2.0, DIALIGN 2 and T-Coffee.
      We perform tests on the effect of introducing these columns on the popular
      benchmark BAliBASE 3. CONCLUSIONS: we show that the inclusion of our partial
      alignment columns, as anchor points, improve on the whole the accuracy of the
      aligner ClustalW on the benchmark BAliBASE 3.

PMID- 20813052
TI  - Sprouty1, a new target of the angiostatic agent 16K prolactin, negatively
      regulates angiogenesis.
AB  - BACKGROUND: Disorganized angiogenesis is associated with several pathologies,
      including cancer. The identification of new genes that control tumor
      neovascularization can provide novel insights for future anti-cancer therapies.
      Sprouty1 (SPRY1), an inhibitor of the MAPK pathway, might be one of these new
      genes. We identified SPRY1 by comparing the transcriptomes of untreated
      endothelial cells with those of endothelial cells treated by the angiostatic
      agent 16 K prolactin (16 K hPRL). In the present study, we aimed to explore the
      potential function of SPRY1 in angiogenesis. RESULTS: We confirmed 16 K hPRL
      induced up-regulation of SPRY1 in primary endothelial cells. In addition, we
      demonstrated the positive SPRY1 regulation in a chimeric mouse model of human
      colon carcinoma in which 16 K hPRL treatment was shown to delay tumor growth.
      Expression profiling by qRT-PCR with species-specific primers revealed that
      induction of SPRY1 expression by 16 K hPRL occurs only in the (murine)
      endothelial compartment and not in the (human) tumor compartment. The regulation
      of SPRY1 expression was NF-kappaB dependent. Partial SPRY1 knockdown by RNA
      interference protected endothelial cells from apoptosis as well as increased
      endothelial cell proliferation, migration, capillary network formation, and
      adhesion to extracellular matrix proteins. SPRY1 knockdown was also shown to
      affect the expression of cyclinD1 and p21 both involved in cell-cycle regulation.
      These findings are discussed in relation to the role of SPRY1 as an inhibitor of
      ERK/MAPK signaling and to a possible explanation of its effect on cell
      proliferation. CONCLUSIONS: Taken together, these results suggest that SPRY1 is
      an endogenous angiogenesis inhibitor.

PMID- 20813053
TI  - Echocardiographic imaging of tricuspid and pulmonary valve abnormalities in
      primary ovarian carcinoid tumor.
AB  - Carcinoid is a rare malignancy originating from enterochromaffin cells and is
      clinically characterized by flushing, diarrhea and bronchospasm, due to secretion
      of vasoactive substances. A dreaded complication is carcinoid heart disease,
      which mainly affects right cardiac chambers, resulting in thickened, immobile and
      retracted tricuspid and pulmonary valves. In the current report, a case of a 60
      year old female presenting with symptoms of right heart failure is described.
      Transthoracic two-dimensional and real-time three-dimensional echocardiography
      findings, as well as biochemical markers, including pro-BNP and NT-pro-BNP, were
      consistent with carcinoid syndrome. The histological diagnosis of carcinoid was
      confirmed after surgical resection of an ovarian mass.

PMID- 20813054
TI  - Relationship between tumor size and disease stage in non-small cell lung cancer.
AB  - BACKGROUND: Whether tumor size and stage distribution are correlated remains
      controversial. The objective is to assess the relationship between tumor size and
      disease stage distribution in non-small cell lung cancer (NSCLC). METHODS: We
      conducted a retrospective analysis of 917 cases of NSCLC that were resected in
      the Cancer Hospital of Fudan University and Shanghai Sixth Hospital between
      January 2000 and February 2009. Tumor sizes were grouped into five categories:
      <=20 mm, 21 to 30 mm, 31 to 50 mm, 51 to 70 mm and >=71 mm. RESULTS: Age and
      tumor size affected stage distribution: patients 60 years or older had a higher
      percentage of N0M0 disease than patients younger than 60 years (61.67% vs.
      44.85%, p < 0.01). The smaller the tumor, the more likely the disease was N0M0
      status (p < 0.05). For tumors <=20 mm in diameter, the proportion of cases with
      N0M0 status was 70.79%, compared to 58.88% for 21 to 30 mm, 48.03% for 31 to 50
      mm, 47.55% for 51 to 70 mm, 33.33% for >=71 mm. The mean (+/- SD) tumor size of
      cases with N0M0 status was 37.17 +/- 21.34 mm, compared to 45.75 +/- 23.19 mm for
      cases with other status. CONCLUSIONS: There is a statistically significant
      relationship between tumor size and distribution of disease stage of primary
      NSCLC tumors: the smaller the tumor, the more likely the disease is N0M0 status.

PMID- 20813056
TI  - Predictors of interstitial lung disease in early systemic sclerosis: a
      prospective longitudinal study of the GENISOS cohort.
AB  - INTRODUCTION: The objective of the present study was to examine the association
      of baseline demographic and clinical characteristics with sequentially obtained
      measurements of forced vital capacity (FVC), expressed as a percentage of the
      predicted value, and to identify predictors of the decline rate in FVC over time
      in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS).
      METHODS: To date, 266 patients have been enrolled in GENISOS, a prospective,
      observational cohort of patients with early systemic sclerosis. In addition to
      pulmonary function tests (PFTs), clinical and laboratory data were obtained from
      each patient. We analyzed 926 FVC measurements utilizing generalized linear mixed
      models. The predictive significance of baseline variables for the decline rate in
      FVC was investigated by the interaction term between the variable and the follow
      up time within the first 3 years after enrollment as well as throughout the
      entire follow-up time. RESULTS: The cohort consisted of 125 white, 54 African
      American, and 77 Hispanic patients with average disease duration of 2.5 years at
      enrollment. The mean follow-up time was 3.8 years, ranging up to 11.4 years. A
      number of baseline variables, including antibody status, African American
      ethnicity, disease type, baseline PFT values, modified Rodnan Skin Score,
      fibrosis on chest radiograph, and lung and skin subscores of the Severity Index,
      were associated with serially measured FVC levels. However, only the presence of
      anti-topoisomerase I antibodies (ATA) was associated with lower FVC levels (P <
      0.001) as well as accelerated decline rate in FVC within the first 3 years of
      follow-up (P = 0.02). None of the baseline variables predicted the rate of
      decline in FVC on long-term follow-up. Patients with rapidly progressive ILD,
      however, were under-represented in the long-term follow-up group because the
      accelerated rate of decline in FVC was associated with poor survival (P = 0.001).
      CONCLUSIONS: Presence of ATA was the only baseline variable associated with
      differential FVC levels, predicting the rate of decline in FVC within the first 3
      years of follow-up. The association of faster decline in FVC with poor survival
      further emphasizes the need for identification of predictive biomarkers by
      collection of genetic information and serial blood samples in cohort studies.

PMID- 20813055
TI  - Side effects of chaperone gene co-expression in recombinant protein production.
AB  - Insufficient availability of molecular chaperones is observed as a major
      bottleneck for proper protein folding in recombinant protein production.
      Therefore, co-production of selected sets of cell chaperones along with foreign
      polypeptides is a common approach to increase the yield of properly folded,
      recombinant proteins in bacterial cell factories. However, unbalanced amounts of
      folding modulators handling folding-reluctant protein species might instead
      trigger undesired proteolytic activities, detrimental regarding recombinant
      protein stability, quality and yield. This minireview summarizes the most recent
      observations of chaperone-linked negative side effects, mostly focusing on DnaK
      and GroEL sets, when using these proteins as folding assistant agents. These
      events are discussed in the context of the complexity of the cell quality network
      and the consequent intricacy of the physiological responses triggered by protein
      misfolding.

PMID- 20813057
TI  - Evaluation of the consequences associated with diffuse vascular disease history
      in patients diagnosed with peripheral arterial disease: estimates from
      Saskatchewan health data.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is caused by narrowing of the
      arteries in the lower extremities. Limited data exist concerning the impact of
      diffuse vascular disease (DVD) on prognosis and costs. Thus, the objective of
      this study is to estimate the impact of DVD on morbidity, mortality and costs.
      METHODS: PAD was identified between 1985 and 1995 and classified by extent of DVD
      at diagnosis: none (PAD only, reference group), prior myocardial infarction (MI),
      prior stroke, prior MI and stroke (MI + stroke), prior transient ischemic attack
      (TIA). Deaths and hospitalizations were identified through December 2000.
      Hospitalization costs were estimated from the Ontario Case Cost Project, reported
      in 2002 $CAD. Proportional hazards analyses measured the impact of vascular
      involvement on mortality while controlling for risk factors (e.g., age,
      cardiovascular history). RESULTS: Overall, 16,439 patients with PAD were
      included; 14.8% had a prior MI, 10.2% a prior stroke, 2.6% prior MI + stroke,
      6.4% prior TIA, two-thirds had PAD only. Median survival was shorter for patients
      with prior MI (9.3 yrs), TIA (6.3), stroke (4.7), and MI+stroke (4.1) versus the
      reference group (9.9, p < 0.05, all comparisons). Analyses revealed that the
      death risk was 60% higher in patients with prior stroke and 84% higher for MI +
      stroke. Atherothrombotic and bleeding event-related costs were $712, $337, $268,
      and $170 higher per patient/year of follow-up in patients with a history of
      MI+stroke, MI, stroke, and TIA, respectively. CONCLUSION: Patients diagnosed with
      PAD with DVD have higher risk of poor outcomes and increased costs.

PMID- 20813059
TI  - Biomechanical testing of implant free wedge shaped bone block fixation for bone
      patellar tendon bone anterior cruciate ligament reconstruction in a bovine model.
AB  - BACKGROUND: The use of an interference fit wedged bone plug to provide fixation
      in the tibial tunnel when using bone-patellar tendon-bone autograft for anterior
      cruciate ligament reconstruction offers many theoretic advantages including the
      potential to offer a more economical and biological alternative to screw
      fixation. This technique has not been subjected to biomechanical testing. We
      hypothesised that a wedged bone plug fixation technique provides equivalent
      tensile load to failure as titanium interference screw fixation. METHODS: In a
      controlled laboratory setting, anterior cruciate ligament reconstruction was
      performed in 36 bovine knees using bone-patella-bone autograft. In 20 knees
      tibial fixation relied upon a standard cuboid bone block and interference screw.
      In eight knees a wedge shaped bone block with an 11 mm by 10 mm base without a
      screw was used. In a further eight knees a similar wedge with a 13 mm by 10 mm
      base was used. Each specimen used a standard 10 mm tibial tunnel. The
      reconstructions were tested biomechanically in a physiological environment using
      an Instron machine to compare ultimate failure loads and modes of failure.
      RESULTS: Statistical analysis revealed no significant difference between wedge
      fixation and screw fixation (p = 0.16), or between individual groups
      (interference screw versus 11 mm versus 13 mm wedge fixation) (P = 0.35).
      CONCLUSIONS: Tibial tunnel fixation using an impacted wedge shaped bone block in
      anterior cruciate ligament reconstruction has comparable ultimate tensile
      strength to titanium interference screw fixation.

PMID- 20813058
TI  - Evolution of duplicated IgH loci in Atlantic salmon, Salmo salar.
AB  - BACKGROUND: The Atlantic salmon (Salmo salar) immunoglobulin heavy chain (IgH)
      locus possesses two parallel IgH isoloci (IGH-A and IGH-B), that are related to
      the genomic duplication event in the family Salmonidae. These duplicated IgH loci
      in Atlantic salmon provide a unique opportunity to examine the mechanisms of
      genome diversity and genome evolution of the IgH loci in vertebrates. In this
      study, we defined the structure of these loci in Atlantic salmon, and sequenced
      24 bacterial artificial chromosome (BAC) clones that were assembled into the IGH
      A (1.1 Mb) and IGH-B (0.9 Mb) loci. In addition, over 7,000 cDNA clones from the
      IgH variable (VH) region have been sequenced and analyzed. RESULTS: The present
      study shows that the genomic organization of the duplicated IgH loci in Atlantic
      salmon differs from that in other teleosts and other vertebrates. The loci
      possess multiple Ctau genes upstream of the CMU region, with three of the Ctau
      genes being functional. Moreover, the duplicated loci possess over 300 VH
      segments which could be classified into 18 families. This is the largest number
      of VH families currently defined in any vertebrate. There were significant
      structural differences between the two loci, indicating that both IGH-A and -B
      loci have evolved independently in the short time after the recent genome
      duplication approximately 60 mya. CONCLUSIONS: Our results indicate that the
      duplication of the IgH loci in Atlantic salmon significantly contributes to the
      increased diversity of the antibody repertoire, as compared with the single IgH
      locus in other vertebrates.

PMID- 20813060
TI  - Schizophrenia, amphetamine-induced sensitized state and acute amphetamine
      exposure all show a common alteration: increased dopamine D2 receptor
      dimerization.
AB  - BACKGROUND: All antipsychotics work via dopamine D2 receptors (D2Rs), suggesting
      a critical role for D2Rs in psychosis; however, there is little evidence for a
      change in receptor number or pharmacological nature of D2Rs. Recent data suggest
      that D2Rs form dimers in-vitro and in-vivo, and we hypothesized that
      schizophrenia, as well as preclinical models of schizophrenia, would demonstrate
      altered dimerization of D2Rs, even though the overall number of D2Rs was
      unaltered. METHODS: We measured the expression of D2Rs dimers and monomers in
      patients with schizophrenia using Western blots, and then in striatal tissue from
      rats exhibiting the amphetamine-induced sensitized state (AISS). We further
      examined the interaction between D2Rs and the dopamine transporter (DAT) by co
      immunoprecipitation, and measured the expression of dopamine D2High receptors
      with ligand binding assays in rat striatum slices with or without acute
      amphetamine pre-treatment. RESULTS: We observed significantly enhanced expression
      of D2Rs dimers (277.7 +/- 33.6%) and decreased expression of D2Rs monomers in
      post-mortem striatal tissue of schizophrenia patients. We found that amphetamine
      facilitated D2Rs dimerization in both the striatum of AISS rats and in rat
      striatal neurons. Furthermore, amphetamine-induced D2Rs dimerization may be
      associated with the D2R-DAT protein-protein interaction as an interfering peptide
      that disrupts the D2R-DAT coupling, blocked amphetamine-induced up-regulation of
      D2Rs dimerization. CONCLUSIONS: Given the fact that amphetamine induces psychosis
      and that the AISS rat is a widely accepted animal model of psychosis, our data
      suggest that D2R dimerization may be important in the pathophysiology of
      schizophrenia and may be a promising new target for novel antipsychotic drugs.

PMID- 20813061
TI  - Efficacy of beta-blocker therapy in symptomatic athletes with exercise-induced
      intra-ventricular gradients.
AB  - BACKGROUND: Upright exercise stress echocardiography (SE) induces significant
      intraventricular gradient (IVG) and systolic anterior motion (SAM) in a large
      proportion of symptomatic athletes, who may therefore benefit from a negative
      inotropic therapy.The purpose of the present study was to assess the effect of
      chronic oral beta blocker therapy on the occurrence of exercise-induced IVG and
      mitral valve SAM, in symptomatic athletes. METHODS: We enrolled 35 symptomatic
      athletes (age = 23 +/- 11 years) with IVG (>30 mmHg) during SE off therapy. All
      repeated SE on chronic oral beta-blocker therapy (atenolol up to 50 mg,
      bisoprolol up to 10 mg, or metoprolol up to 100 mg daily according to physician
      driven choice). RESULTS: On therapy, there was during SE a reduction in IVG (35
      off vs 17 on beta blocker, p < 0.01), decrease of IVG (102 +/- 34 mmHg off vs 69
      +/- 24 mmHg on beta blocker, p < 0.01), peak heart rate (178 +/- 15 bpm off vs
      157 +/- 9 bpm on beta blocker), SAM (24 off vs 9 on beta blocker, p < 0.001),
      symptoms during SE (17 off vs 2 on beta blocker p < 0.001), ST segment depression
      (13 off vs 2 on beta blocker, p < 0.001). CONCLUSIONS: In athletes with positive
      screening on medical evaluation for sports practice and IVG on exertion,
      treatment with oral beta blockers improved symptoms in the large majority of
      patients. Symptomatic benefit was mirrored by objective evidence of improvement
      of echocardiographic signs of obstruction (IVG and SAM) and reduction of ischemia
      like electrocardiographic changes.

PMID- 20813062
TI  - Feasibility, reliability and validity of health-related quality of life
      questionnaire among adult pulmonary tuberculosis patients in urban Uganda: cross
      sectional study.
AB  - BACKGROUND: Despite the availability of standard instruments for evaluating
      health-related quality life (HRQoL), the feasibility, reliability, and validity
      of such instruments among tuberculosis (TB) patients in different populations of
      sub-Saharan Africa where TB burden is of concern, is still lacking. OBJECTIVE: We
      established the feasibility, reliability, and validity of the Medical Outcomes
      Survey (MOS) in assessing HRQoL among patients with pulmonary tuberculosis in
      Kampala, Uganda. METHODS: In a cross-sectional study, 133 patients with known HIV
      status and confirmed pulmonary TB disease were recruited from one public and one
      private hospital. Participants were enrolled based on duration of TB treatment
      according to the following categories: starting therapy, two months of therapy,
      and eight completed months of therapy. A translated and culturally adapted
      standardized 35-item MOS instrument was administered by trained interviewers. The
      visual analogue scale (VAS) was used to cross-validate the MOS. RESULTS: The MOS
      instrument was highly acceptable and easily administered. All subscales of the
      MOS demonstrated acceptable internal consistency with Cronbach's alpha above 0.70
      except for role function that had 0.65. Each dimension of the MOS was highly
      correlated with the dimension measured concurrently using the VAS providing
      evidence of validity. Construct validity demonstrated remarkable differences in
      the functioning status and well-being among TB patients at different stages of
      treatment, between patients attending public and private hospitals, and between
      men and women of older age. Patients who were enrolled from public hospital had
      significantly lower HRQoL scores (0.78 (95% confidence interval (CI); 0.64-0.95))
      for perceived health but significantly higher HRQoL scores (1.15 (95% CI; 1.06
      1.26)) for health distress relative to patients from private hospital. Patients
      who completed an 8 months course of TB therapy had significantly higher HRQoL
      scores for perceived health (1.93 (95% CI; 1.19-3.13)), health distress subscales
      (1.29 (95% CI; 1.04-1.59)) and mental health summary scores (1.27 (95% CI; 1.09
      1.48)) relative to patients that were starting therapy in multivariable analysis.
      Completion of 8 months TB therapy among patients who were recruited from the
      public hospital was associated with a significant increase in HRQoL scores for
      quality of life subscale (1.26 (95% CI; 1.08-1.49)), physical health summary
      score (1.22 995% CI; 1.04-1.43)), and VAS (1.08 (95% CI; 1.01-1.15)) relative to
      patients who were recruited from the private hospital. Older men were
      significantly associated with lower HRQoL scores for physical health summary
      score (0.68 (95% CI; 0.49-0.95)) and VAS (0.87 (95% CI; 0.75-0.99)) relative to
      women of the same age group. No differences were seen between HIV positive and
      HIV negative patients. CONCLUSION: The study provides evidence that the MOS
      instrument is valid, and reliably measures HRQoL among TB patients, and can be
      used in a wide variety of study populations. The HRQoL differed by hospital
      settings, by duration of TB therapy, and by gender in older age groups.

PMID- 20813063
TI  - Pneumomediastinum as a complication of emphysematous cholecystitis: case report.
AB  - BACKGROUND: Emphysematous cholecystitis is a variant of acute cholecystitis which
      is generally caused by gas-forming organisms. Emphysematous cholecystitis may
      cause gas spreading within the subcutaneous tissue, peritoneal cavity and
      retroperitoneum. CASE PRESENTATION: We present a case of emphysematous
      cholecystitis in a middle-aged diabetic patient who, postoperatively, presented
      edema in both flanks and left chest crepitation on palpation, associated with
      hemodynamic worsening. Computed tomography scan of the chest and abdomen revealed
      a large pneumomediastinum, pneumoretroperitoneum, gas in subcutaneous tissue and
      flank abscesses. In both blood and surgical wound exudate cultures, Escherichia
      coli was found. CONCLUSION: Emphysematous cholecystitis should be considered as a
      possible cause of pneumomediastinum.

PMID- 20813064
TI  - 18F-FDG PET/CT-based gross tumor volume definition for radiotherapy in head and
      neck cancer: a correlation study between suitable uptake value threshold and
      tumor parameters.
AB  - BACKGROUND: To define a suitable threshold setting for gross tumor volume (GTV)
      when using 18Fluoro-deoxyglucose positron emission tomography and computed
      tomogram (PET/CT) for radiotherapy planning in head and neck cancer (HNC).
      METHODS: Fifteen HNC patients prospectively received PET/CT simulation for their
      radiation treatment planning. Biological target volume (BTV) was derived from
      PET/CT-based GTV of the primary tumor. The BTVs were defined as the isodensity
      volumes when adjusting different percentage of the maximal standardized uptake
      value (SUVmax), excluding any artifact from surrounding normal tissues. CT-based
      primary GTV (C-pGTV) that had been previously defined by radiation oncologists
      was compared with the BTV. Suitable threshold level (sTL) could be determined
      when BTV value and its morphology using a certain threshold level was observed to
      be the best fitness of the C-pGTV. Suitable standardized uptake value (sSUV) was
      calculated as the sTL multiplied by the SUVmax. RESULTS: Our result demonstrated
      no single sTL or sSUV method could achieve an optimized volumetric match with the
      C-pGTV. The sTL was 13% to 27% (mean, 19%), whereas the sSUV was 1.64 to 3.98
      (mean, 2.46). The sTL was inversely correlated with the SUVmax [sTL = -0.1004 Ln
      (SUVmax) + 0.4464; R2 = 0.81]. The sSUV showed a linear correlation with the
      SUVmax (sSUV = 0.0842 SUVmax + 1.248; R2 = 0.89). The sTL was not associated with
      the value of C-pGTVs. CONCLUSION: In PET/CT-based BTV for HNC, a suitable
      threshold or SUV level can be established by correlating with SUVmax rather than
      using a fixed threshold.

PMID- 20813065
TI  - Long-term effect of stereotactic body radiation therapy for primary
      hepatocellular carcinoma ineligible for local ablation therapy or surgical
      resection. Stereotactic radiotherapy for liver cancer.
AB  - BACKGROUND: We evaluated the long-term effect of stereotactic body radiation
      therapy (SBRT) for primary small hepatocellular carcinoma (HCC) ineligible for
      local therapy or surgery. METHODS: Forty-two HCC patients with tumors <= 100 cc
      and ineligible for local ablation therapy or surgical resection were treated with
      SBRT: 30-39 Gy with a prescription isodose range of 70-85% (median 80%) was
      delivered daily in three fractions. Median tumor volume was 15.4 cc (3.0-81.8)
      and median follow-up duration 28.7 months (8.4-49.1). RESULTS: Complete response
      (CR) for the in-field lesion was initially achieved in 59.6% and partial response
      (PR) in 26.2% of patients. Hepatic out-of-field progression occurred in 18
      patients (42.9%) and distant metastasis developed in 12 (28.6%) patients. Overall
      in-field CR and overall CR were achieved in 59.6% and 33.3%, respectively.
      Overall 1-year and 3-year survival rates were 92.9% and 58.6%, respectively. In
      field progression-free survival at 1 and 3 years was 72.0% and 67.5%,
      respectively. Patients with smaller tumor had better in-field progression-free
      survival and overall survival rates (<32 cc vs. >=32 cc, P < 0.05). No major
      toxicity was encountered but one patient died with extrahepatic metastasis and
      radiation-induced hepatic failure. CONCLUSIONS: SBRT is a promising noninvasive
      treatment for small HCC that is ineligible for local treatment or surgical
      resection.

PMID- 20813066
TI  - Development of temporal modelling for forecasting and prediction of malaria
      infections using time-series and ARIMAX analyses: a case study in endemic
      districts of Bhutan.
AB  - BACKGROUND: Malaria still remains a public health problem in some districts of
      Bhutan despite marked reduction of cases in last few years. To strengthen the
      country's prevention and control measures, this study was carried out to develop
      forecasting and prediction models of malaria incidence in the endemic districts
      of Bhutan using time series and ARIMAX. METHODS: This study was carried out
      retrospectively using the monthly reported malaria cases from the health centres
      to Vector-borne Disease Control Programme (VDCP) and the meteorological data from
      Meteorological Unit, Department of Energy, Ministry of Economic Affairs. Time
      series analysis was performed on monthly malaria cases, from 1994 to 2008, in
      seven malaria endemic districts. The time series models derived from a
      multiplicative seasonal autoregressive integrated moving average (ARIMA) was
      deployed to identify the best model using data from 1994 to 2006. The best-fit
      model was selected for each individual district and for the overall endemic area
      was developed and the monthly cases from January to December 2009 and 2010 were
      forecasted. In developing the prediction model, the monthly reported malaria
      cases and the meteorological factors from 1996 to 2008 of the seven districts
      were analysed. The method of ARIMAX modelling was employed to determine
      predictors of malaria of the subsequent month. RESULTS: It was found that the
      ARIMA (p, d, q) (P, D, Q)s model (p and P representing the auto regressive and
      seasonal autoregressive; d and D representing the non-seasonal differences and
      seasonal differencing; and q and Q the moving average parameters and seasonal
      moving average parameters, respectively and s representing the length of the
      seasonal period) for the overall endemic districts was (2,1,1)(0,1,1)12; the
      modelling data from each district revealed two most common ARIMA models including
      (2,1,1)(0,1,1)12 and (1,1,1)(0,1,1)12. The forecasted monthly malaria cases from
      January to December 2009 and 2010 varied from 15 to 82 cases in 2009 and 67 to
      149 cases in 2010, where population in 2009 was 285,375 and the expected
      population of 2010 to be 289,085. The ARIMAX model of monthly cases and climatic
      factors showed considerable variations among the different districts. In general,
      the mean maximum temperature lagged at one month was a strong positive predictor
      of an increased malaria cases for four districts. The monthly number of cases of
      the previous month was also a significant predictor in one district, whereas no
      variable could predict malaria cases for two districts. CONCLUSIONS: The ARIMA
      models of time-series analysis were useful in forecasting the number of cases in
      the endemic areas of Bhutan. There was no consistency in the predictors of
      malaria cases when using ARIMAX model with selected lag times and climatic
      predictors. The ARIMA forecasting models could be employed for planning and
      managing malaria prevention and control programme in Bhutan.

PMID- 20813067
TI  - Anti-CDC25B autoantibody predicts poor prognosis in patients with advanced
      esophageal squamous cell carcinoma.
AB  - BACKGROUND: The oncogene CDC25B phosphatase plays an important role in cancer
      cell growth. We have recently reported that patients with esophageal squamous
      cell carcinoma (ESCC) have significantly higher serum levels of CDC25B
      autoantibodies (CDC25B-Abs) than both healthy individuals and patients with other
      types of cancer; however, the potential diagnostic or prognostic significance of
      CDC25B-Abs is not clear. The aim of this study is to evaluate the clinical
      significance of serum CDC25B-Abs in patients with ESCC. METHODS: CDC25B
      autoantibodies were measured in sera from both 134 patients with primary ESCC and
      134 healthy controls using a reverse capture enzyme-linked immunosorbent assay
      (ELISA) in which anti-CDC25B antibodies bound CDC25B antigen purified from Eca
      109 ESCC tumor cells. The clinicopathologic significance of CDC25B serum
      autoantibodies was compared to that of the tumor markers carcinoembryonic antigen
      (CEA), squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragment
      antigen 21-1(CYFRA21-1). RESULTS: Higher levels of CDC25B autoantibodies were
      present in sera from patients with ESCC (A450 = 0.917, SD = 0.473) than in sera
      from healthy control subjects (A450 = 0.378, SD = 0.262, P < 0.001). The area
      under the receiver operating characteristic (ROC) curve for CDC25B-Abs was 0.870
      (95% CI: 0.835-0.920). The sensitivity and specificity of CDC25B-Abs for
      detection of ESCC were 56.7% and 91.0%, respectively, when CDC25-Abs-positive
      samples were defined as those with an A450 greater than the cut-off value of
      0.725. Relatively few patients tested positive for the tumor markers CEA, SCC-Ag
      and CYFRA21-1 (13.4%, 17.2%, and 32.1%, respectively). A significantly higher
      number of patients with ESCC tested positive for a combination of CEA, SCC,
      CYFRA21-1 and CDC25B-Abs (64.2%) than for a combination of CEA, SCC-Ag and
      CYFRA21-1 (41.0%, P < 0.001). The concentration of CDC25B autoantibodies in serum
      was significantly correlated with tumor stage (P < 0.001). Although examination
      of the total patient pool showed no obvious relationship between CDC25B
      autoantibodies and overall survival, in the subgroup of patients with stage III
      IV tumors, the cumulative five-year survival rate of CDC25B-seropositive patients
      was 6.7%, while that of CDC25B-seronegative patients was 43.4% (P = 0.001, log
      rank). In the N1 subgroup, the cumulative five-year survival rate of CDC25B
      seropositive patients was 13.6%, while that of CDC25B-seronegative patients was
      54.5% (P = 0.040, log-rank). CONCLUSIONS: Detection of serum CDC25B-Abs is
      superior to detection of the tumor markers CEA, SCC-Ag and CYFRA21-1 for
      diagnosis of ESCC, and CDC25B-Abs are a potential prognostic serological marker
      for advanced ESCC.

PMID- 20813068
TI  - Fast and accurate protein substructure searching with simulated annealing and
      GPUs.
AB  - BACKGROUND: Searching a database of protein structures for matches to a query
      structure, or occurrences of a structural motif, is an important task in
      structural biology and bioinformatics. While there are many existing methods for
      structural similarity searching, faster and more accurate approaches are still
      required, and few current methods are capable of substructure (motif) searching.
      RESULTS: We developed an improved heuristic for tableau-based protein structure
      and substructure searching using simulated annealing, that is as fast or faster
      and comparable in accuracy, with some widely used existing methods. Furthermore,
      we created a parallel implementation on a modern graphics processing unit (GPU).
      CONCLUSIONS: The GPU implementation achieves up to 34 times speedup over the CPU
      implementation of tableau-based structure search with simulated annealing, making
      it one of the fastest available methods. To the best of our knowledge, this is
      the first application of a GPU to the protein structural search problem.

PMID- 20813069
TI  - Persistent high fertility in Uganda: young people recount obstacles and enabling
      factors to use of contraceptives.
AB  - BACKGROUND: High fertility among young people aged 15-24 years is a public health
      concern in Uganda. Unwanted pregnancy, unsafe induced abortions and associated
      high morbidity and mortality among young women may be attributed to low
      contraceptive use. This study aims at exploring reasons for low contraceptive use
      among young people. METHODS: In 16 focus group discussions, the views of young
      people about obstacles and enabling factors to contraceptive use in Mityana and
      Mubende districts, Uganda were explored. The groups were homogeneously composed
      by married and unmarried men and women, between the ages of 15-24. The data
      obtained was analyzed using qualitative content analysis. RESULTS: Young men and
      women described multiple obstacles to contraceptive use. The obstacles were
      categorized as misconceptions and fears related to contraception, gender power
      relations, socio-cultural expectations and contradictions, short term planning,
      and health service barriers. Additionally, young people recounted several
      enabling factors that included female strategies to overcome obstacles, changing
      perceptions to contraceptive use, and changing attitude towards a small family
      size. CONCLUSIONS: Our findings suggest changing perceptions and behavior shift
      towards contraceptive use and a small family size although obstacles still exist.
      Personalized strategies to young women and men are needed to motivate and assist
      young people plan their future families, adopt and sustain use of contraceptives.
      Reducing obstacles and reinforcing enabling factors through education, culturally
      sensitive behavior change strategies have the potential to enhance contraceptives
      use. Alternative models of contraceptive service delivery to young people are
      proposed.

PMID- 20813070
TI  - Comparison of two approaches for measuring household wealth via an asset-based
      index in rural and peri-urban settings of Hunan province, China.
AB  - BACKGROUND: There are growing concerns regarding inequities in health, with
      poverty being an important determinant of health as well as a product of health
      status. Within the People's Republic of China (P.R. China), disparities in socio
      economic position are apparent, with the rural-urban gap of particular concern.
      Our aim was to compare direct and proxy methods of estimating household wealth in
      a rural and a peri-urban setting of Hunan province, P.R. China. METHODS: We
      collected data on ownership of household durable assets, housing characteristics,
      and utility and sanitation variables in two village-wide surveys in Hunan
      province. We employed principal components analysis (PCA) and principal axis
      factoring (PAF) to generate household asset-based proxy wealth indices.
      Households were grouped into quartiles, from 'most wealthy' to 'most poor'. We
      compared the estimated household wealth for each approach. Asset-based proxy
      wealth indices were compared to those based on self-reported average annual
      income and savings at the household level. RESULTS: Spearman's rank correlation
      analysis revealed that PCA and PAF yielded similar results, indicating that
      either approach may be used for estimating household wealth. In both settings
      investigated, the two indices were significantly associated with self-reported
      average annual income and combined income and savings, but not with savings
      alone. However, low correlation coefficients between the proxy and direct
      measures of wealth indicated that they are not complementary. We found wide
      disparities in ownership of household durable assets, and utility and sanitation
      variables, within and between settings. CONCLUSION: PCA and PAF yielded almost
      identical results and generated robust proxy wealth indices and categories.
      Pooled data from the rural and peri-urban settings highlighted structural
      differences in wealth, most likely a result of localized urbanization and
      modernization. Further research is needed to improve measurements of wealth in
      low-income and transitional country contexts.

PMID- 20813072
TI  - What do we want to know about the relationship of wealth or income to nutrition?

PMID- 20813071
TI  - Autoinflammatory syndromes: diagnosis and management.
AB  - During the last decades the description of autoinflammatory syndromes induced
      great interest among the scientific community. Mainly rheumatologists,
      immunologists and pediatricians are involved in the discovery of etiopathogenesis
      of these syndromes and in the recognition of affected patients. In this paper we
      will discuss the most important clues of monogenic and non-genetic inflammatory
      syndromes to help pediatricians in the diagnosis and treatment of these diseases.

PMID- 20813074
TI  - Psychosocial interventions for dementia patients in long-term care.
AB  - BACKGROUND: Psychosocial interventions in long-term care have the potential to
      improve the quality of care and quality of life of persons with dementia. Our aim
      is to explore the evidence and consensus on psychosocial interventions for
      persons with dementia in long-term care. METHODS: This study comprises an
      appraisal of research reviews and of European, U.S. and Canadian dementia
      guidelines. RESULTS: Twenty-eight reviews related to long-term care psychosocial
      interventions were selected. Behavioral management techniques (such as behavior
      therapy), cognitive stimulation, and physical activities (such as walking) were
      shown positively to affect behavior or physical condition, or to reduce
      depression. There are many other promising interventions, but methodological
      weaknesses did not allow conclusions to be drawn. The consensus presented in the
      guidelines emphasized the importance of care tailored to the needs and
      capabilities of persons with dementia and consideration of the individual's life
      context. CONCLUSIONS: Long-term care offers the possibility for planned care
      through individualized care plans, and consideration of the needs of persons with
      dementia and the individual life context. While using recommendations based on
      evidence and consensus is important to shape future long-term care, further well
      designed research is needed on psychosocial interventions in long-term care to
      strengthen the evidence base for such care.

PMID- 20813075
TI  - A short-form version of the Boston Naming Test for language screening in dementia
      in a bilingual rural community in Galicia (Spain).
AB  - BACKGROUND: Aphasia, one of the core symptoms of cortical dementia, is routinely
      evaluated using graded naming tests like the Boston Naming Test (BNT). However,
      the application of this 60-item test is time-consuming and shortened versions
      have been devised for screening. The hypothesis of this research is that a
      specifically designed shortened version of the BNT could replace the original 60
      item BNT as part of a mini-battery for screening for dementia. The objective of
      this study was to design a short version of the BNT for a rural population in
      Galicia (Spain). METHODS: A clinic group of 102 patients including 43 with
      dementia was recruited along with 78 healthy volunteers. The clinic and control
      groups were scored on the Spanish version of the Mini-mental State Examination
      (MMSE) and BNT. In addition, the clinic group was tested with standard
      neuropsychological instruments and underwent brain investigations and routine
      neurological examination. BNT items with specificity and sensitivity above 0.5
      were selected to compose a short battery of 11 pictures named BNTOu11. ANOVA and
      mean comparisons were made for MMSE and BNT versions. Receiver operating
      characteristics (ROC) curves and internal consistency were calculated. RESULTS:
      Areas under ROC curves (AUC) did not show statistically significant differences;
      therefore BNTOu11's AUC (0.814) was similar to the 60-item BNT versions (0.785
      and 0.779), to the short versions from Argentina (0.772) and Andalusia (0.799)
      and to the Spanish MMSE (0.866). BNTOu11 had higher internal consistency than the
      other short versions. CONCLUSIONS: BNTOu11 is a useful and time-saving method as
      part of a battery for screening for dementia in a psychogeriatric outpatient
      unit.

PMID- 20813076
TI  - Depression literacy among older Chinese immigrants in Canada: a comparison with a
      population-based survey.
AB  - BACKGROUND: Investigations of mental health literacy are important because the
      recognition of a mental health problem is the first step in seeking appropriate
      mental health care. Lack of recognition is a significant barrier to accessing
      mental health resources. Older Chinese immigrants are at increased risk for
      depression; however, there is no research investigating their depression
      literacy, including their beliefs about treatment, etiology, and prognosis.
      METHODS: This study investigated depression literacy among 53 older Chinese
      immigrants in Canada (aged 55-87 years) and compared their literacy to Canadian
      born participants of the same age who were part of a larger population-based
      survey. Depression literacy was assessed through interviews using a case vignette
      and included the following indices: rates of correct identification of
      depression; perceived efficacy of various people, professions and treatments; and
      perceptions of etiology and prognosis. RESULTS: In the Chinese sample, 11.3%
      correctly identified depression in the case vignette. In contrast, 74.0% of
      participants in the population-based survey correctly identified depression.
      Differences in the perceptions of helpful people and interventions, etiology, and
      prognosis were also noted between the samples. Both samples strongly endorsed
      physical activity as helpful in the treatment of depression. CONCLUSIONS: In
      light of these results, it is clear that older Chinese immigrants would benefit
      from information regarding the symptoms, etiology, and treatment of depression,
      and that this information may begin to address the serious underutilization of
      mental health services among this group. Our discussion highlights practice
      implications and promising interventions.

PMID- 20813077
TI  - The more physical inactivity, the more agitation in dementia.
AB  - Epidemiological studies show a close relationship between physical activity and
      cognition. A causal relationship between physical activity and cognition has been
      observed in children, adolescents, older people without dementia, and in older
      people in a very early stage of dementia. Considering these positive effects, we
      argue that a decline in physical activity has a detrimental effect on cognition
      and behavior in patients with dementia. Merely living in a nursing home reduces
      the level of physical activity. The level of physical activity may even be
      reduced to a minimum when physical restraints are applied. The use of physical
      restraints coincides with stress, further aggravating the already existing
      neuropathology, which may increase stress and agitation even more. Exercise may
      reduce stress and agitation.

PMID- 20813078
TI  - Gas cascade amplification in ultra-high-resolution environmental scanning
      electron microcopy.
AB  - We describe a feedback mechanism in the gas cascade amplification process used in
      magnetic immersion lens environmental scanning electron microcopy (ESEM).
      Feedback dominates gas gain under the conditions typically used for ultra-high
      resolution ESEM and gives rise to novel dependencies of the imaging signal and
      noise on microscope operating parameters. It is ascribed tentatively to the
      generation of free electrons upon de-excitation of metastable species in the gas
      cascade. The results have implications for optimization of ESEM systems for
      applications such as critical dimension metrology and real-time imaging of
      nanostructure growth by gas mediated electron beam induced deposition.

PMID- 20813079
TI  - Characterization of healthy and fluorotic enamel by atomic force microscopy.
AB  - The aim was to characterize the external structure, roughness, and absolute depth
      profile (ADP) of fluorotic enamel compared with healthy enamel. Eighty extracted
      human molars were classified into four groups [TFI: 0, control (C); 1-3, mild
      (MI); 4-5, moderate (MO); 6-9, severe fluorosis (S)] according to the Thylstrup
      Fejerskov Index (TFI). All samples were analyzed by atomic force microscopy.The
      mean values of enamel surface roughness (ESR) in nm were: Group C, 92.6; Group
      MI, 188.8; Group MO, 246.9; and Group S, 532.2. The mean values of absolute depth
      profile in nm were: C, 1,065.7; MI, 2,360.7; MO, 2,536.7; and S, 6,146.2. The
      differences between mean ESR and mean ADP among groups were statistically
      significant (p < 0.05). This structural study confirms at the nanometer level
      that there is a positive association between fluorosis severity, ESR, and ADP,
      and there is an association with the clinical findings of fluorosis measured by
      TFI as well.

PMID- 20813081
TI  - [Evaluation of preserved insulin secretion in children and adolescents with type
      1 diabetes].
AB  - INTRODUCTION: The pathogenesis of type 1 diabetes is connected with immune
      mediated beta-cell destruction leading to insulin deficiency. The majority of
      patients will become completely incapable of insulin secretion within a few
      years, however, some individuals will have persistent beta-cell function years
      after the diagnosis of diabetes. Despite clinical symptoms of insulin deficiency,
      residual beta-cell secretion can modify the clinical course and can be an
      independent factor influencing the delay of development of chronic diabetic
      complications. The aim of the study was to compare a 10-year clinical course in
      children with type 1 diabetes with and without preserved beta-cell secretion.
      MATERIAL AND METHODS: 72 children and adolescents with diabetes lasting for
      minimum 10 years and available biological material to c-peptide evaluation (3-4
      years and 10 years from the onset of diabetes) were chosen from 768 children with
      type 1 diabetes. We assessed fasting c-peptide and recruited 23 out of 72
      patients whose concentration of c-peptide was below or over 0.23 ng/ml at all
      time points (this cut point derives from the definition of preserved beta-cell
      function according to DCCT). Afterwards we divided children into two subgroups: A
      (n=13) - without insulin secretion and B (n=10) - with preserved beta-cell
      function during 10 years of observation. We assessed markers of beta-cell
      autoimmunity (ICA, GADA, IA2, IAA) in the examined groups. Insulin requirement
      and concentration of glycated hemoglobin (assessed as the year mean from four
      measurements in each year) were compared between group A and B. RESULTS: The age
      at onset of diabetes in children from both examined groups was similar. All
      children from group B and 12/13 from group A were positive for at least one type
      of the screened autoantibodies. There was no difference in insulin requirement
      between the groups (p=0.6). The level of glycated hemoglobin was significantly
      lower in group B during a 10-year observational period (p=0.04). CONCLUSION:
      Repeated measures of c-peptide can enable us to define two groups of patients
      with immune-mediated diabetes with different levels of disease and metabolic
      control.

PMID- 20813082
TI  - [Optimization of monogenic diabetes screening programme--initial report on
      recruitment efficacy of the TEAM project].
AB  - INTRODUCTION: Due to the lack of precise diagnostic criteria, current search
      strategy for monogenic diabetes is predominantly based on atypical clinical
      course of diabetes and intuition of the attending physician. Yet another issue is
      the common view that monogenic diabetes is rare. It discourages from performing
      deepened diagnostics and makes it difficult to gain experience necessary to
      select appropriate patients for genetic examination. AIM OF THE STUDY: Estimating
      the true incidence of patients with a high probability of monogenic background of
      the disease and compare their search strategies based on clinical practice or
      structured databases. MATERIAL AND METHODS: The authors compared the current
      strategy of selecting candidates for screening with a directed search strategy
      based on immunologic (lack of islet autoantibodies), functional (presence or
      complete lack of c-peptide at onset and follow-up) and familial (dominant pattern
      of inheritance) criteria. The number of patients selected for the screening was
      chosen as efficacy measure selected among 1281 diabetic patients diagnosed and
      treated between 1983-2009. RESULTS: Screening based on clinical assessment
      yielded 37 patients (2.9%) chosen for genetic screening. Criteria used by the
      physicians were based on up-to-date guidelines and unusual clinical course.
      Active search of the database according to predefined criteria resulted in
      selecting: 121 patients (9.4%) with likely monogenic background of diabetes (71 -
      lack of autoantibodies, 8 - normal C-peptide, 6 - lack of both c-peptide and
      autoantibodies, 36 - diabetes in at least one parent). The difference in
      screening efficacy was statistically significant (p <0.0001). CONCLUSIONS:
      Periodic reevaluation of patients' data allows a significant increase in the
      number of candidates subjected to genetic screening and potentially achieving
      beneficial therapeutic effects by means of pharmacogenetics.

PMID- 20813083
TI  - [L-carnitine decreases oxidative stress induced by experimental hypobaric
      hypoxia].
AB  - INTRODUCTION: It is known that exposure to severe hypobaric hypoxia induces
      changes of reactive oxygen species (ROS) and antioxidant systems. L-carnitine, a
      natural compound, has an antioxidant effect and decreases lipid peroxidation. The
      aim of this study was to investigate the protective effects of L-carnitine
      treatment on oxidative stress induced by exposure to hypobaric hypoxia. MATERIAL
      AND METHODS: 30 male Wistar rats were divided into 3 equal-size groups: 1st group
      - a control group, kept in normoxic conditions; 2nd group - rats exposed to
      hypobaric hypoxia in the barochamber (simulated high altitude equivalent to 5500
      meters) for a 14-day placebo; 3rd group - rats exposed to hypobaric hypoxia for
      14 days and treated with L-carnitine (L-carnitine, 100 mg/kg) every day. After 14
      days, the serum levels of lipid peroxides expressed by the value of
      malondialdehyde (MDA), and the serum levels of carbonylated proteins (CP),
      glutathione (GSH) and donor hydrogen ability (DHA) were determined for all rats.
      RESULTS: The results indicated an increase in MDA and CP levels, after the
      exposure to hypobaric hypoxia. L-carnitine significantly decreased (p <0.05) the
      levels of the MDA and CP and significantly increased (p <0.05) the serum
      antioxidant capacity: glutathione and DHA. CONCLUSION: This study suggests that
      the administration of L-carnitine can be beneficial in attenuating the oxidative
      stress associated with exposure to high altitude.

PMID- 20813084
TI  - [Overweight, obesity and metabolic syndrome in children with type 1 diabetes
      melllitus].
AB  - INTRODUCTION: Obesity can be an additional risk factor for developing
      cardiovascular diseases in patients with diabetes. Aim of the study was the
      assessment of overweight, obesity and other elements of the metabolic syndrome in
      children with type 1 diabetes mellitus. MATERIAL AND METHODS: 300 children
      treated with insulin at least one year were enrolled in the study. In the
      examined group anthropometric data, data concerned with diabetes and additional
      laboratory tests including risk factors for cardiovascular diseases were
      assessed. RESULTS: The median age of the examined group was 13.7 years. The body
      mass deficiency was noted in 0.66%, normal body mass in 71.6%, overweight in
      15.3% and obesity in 12.3%. The abdominal obesity was noted in 16.0% of children.
      The rise in the body weight between 3-6 months from the beginning of the insulin
      therapy and the present assessment was statistically significant. Children with
      normal weight had a better metabolic control in comparison to children with
      overweight/obesity. Girls had a higher rise in body mass index values between the
      time of diagnosis and the present investigation compared to boys. Higher values
      of blood pressure or hypertension were noted in 16.6% of children. Altogether in
      25.3% of children some dyslipidemia was observed. The metabolic syndrome criteria
      were noted in: 28.0% - one criterion, 13.0% - two criteria, and 0.3% - three
      criteria. CONCLUSIONS: The population of children with type 1 diabetes is
      characterized by high frequency of overweight/obesity, abdominal obesity,
      dyslipidemia and hypertension. The features of metabolic syndrome are less
      frequent. It is worthwhile to monitor the risk for development of cardiovascular
      diseases in this group of children.

PMID- 20813085
TI  - [Agility in treatment of children with type 1 diabetes--pilot study].
AB  - INTRODUCTION: Physical activity is a very important element in treatment of
      children with type 1 diabetes. However, it is difficult to find suitable
      exercises for the children due to their specific needs and psychophysiological
      condition. The aim of this study was to examine the effects of agility as a
      physical activity used to improve parameters of metabolic control in children
      with type 1 diabetes. Additionally, we hope that this form of recreation could
      induce a more health-oriented behavior in children. MATERIAL AND METHODS: The
      experimental group consisted of seven girls aged 8-10 years, the patients of the
      Clinic of Pediatrics, Endocrinology, Diabetology, Metabolic Disorders and
      Cardiology of the Developmental Age in Szczecin. The children were qualified for
      the study after the prior assessment of their metabolic control under the
      conditions of the one-day hospital stay program. The physical condition of the
      patients was controlled with a 6-minute walk test and the test of perceived
      exertion (Borg scale). All the patients were treated using a personal insulin
      pump and the basal-bolus therapy. The applied research method used the scheme of
      physical exercise performed 3 times a week, 45 min each, reaching the intensity
      of 75% of the maximum heart rate under effort performed by a given patient.
      Before the exercises and directly after their completion, sugar level was
      measured in the blood of the patients (Accu-chek Active). During the exercises,
      the heart rate was measured with a pulsometer Bauer PM 80. The exercises included
      outdoor games and agility sessions. Especially the latter received a positive
      response and high involvement. This form includes a dog going through an obstacle
      course, with a child as a guide. RESULTS AND CONCLUSIONS: After three months of
      the exercise scheme, the analysis of the collected results showed a statistically
      significant (p <0.05) decrease in the insulin doses (bolus) during morning hours
      (7-8 am), and in the evening at 9 pm and 10.30 pm, with an unchanged basal. No
      such decrease was observed in the control group. This study showed that an
      interesting physical activity resulted in a more eager and systematic effort
      among examined diabetic children. Its proper organization in time may help in the
      metabolic control in children with type 1 diabetes.

PMID- 20813086
TI  - [Somatic constitution and the ability to maintain dynamic body equilibrium in
      girls practicing rhythmic gymnastics].
AB  - INTRODUCTION: The greatest similarities in body constitution were noted in
      competitors practising the same discipline. The similarities increase with the
      training level. A typical body constitution for a given discipline not only
      favourably affects athletic performance, but is also the factor preventing
      sportsrelated contusions. The ability to maintain body equilibrium, together with
      somatic constitution, are the basic selective criteria in rhythmic gymnastics.
      AIM OF THE STUDY: The objective of this paper was to determine somatotypes, to
      evaluate the ability to maintain dynamic body equilibrium in girls practicing
      rhythmic gymnastics and to develop model characteristics enabling early diagnosis
      of the disorders equilibrium system function. MATERIAL AND METHODS: The sample
      comprised 19 girls aged 8-11 years, practising rhythmic gymnastics. For the
      evaluation of the competitors' somatotypes, the Heath-Carter method was used,
      based on the classic concept of Sheldon's body constitution components. Body
      equilibrium level was evaluated by means of posturography. RESULTS: The mean
      values of the endomorphic component I, mesomorphic component II and ectomorphic
      component III in the gymnasts were 2.65+/-1.29, 2.45+/-0.37 and 3.95+/-0.64
      respectively. The mean body mass index (BMI) value for this cohort was 15.32,
      which means advanced slimness. The level of dynamic equilibrium is determined by
      the following mean values: the time of reaching the equilibrium, the way of
      reaching it and the duration of stay at the defined point. The model of above
      mentioned indicates was developed based on the analysis of it's best results.
      CONCLUSION: Body constitution type in the qualified gymnasts is characterised by
      the prevalence of the ectomorphic component. The study results indicate that
      female gymnasts are generally slim and lean. It is necessary to monitor BMI in
      order to exclude weight-related disorders and to observe the changes with age.
      The poorest result was found when the gymnasts bent in the backward direction as
      this body position is most difficult to assume and to maintain body equilibrium
      as compared to all other directions.

PMID- 20813087
TI  - [Evaluation of mental development of children with congenital hypothyroidism
      detected in screening test--personal observations].
AB  - INTRODUCTION: Thyroid hormones are crucial for a proper development of the
      central nervous system (CNS), skeleton and tooth buds. They are important from
      the early stages of fetal development. The aim of the study was to evaluate the
      mental development of children with congenital hypothyroidism detected in
      screening and to determine the effect of TSH, level of thyroid hormones during
      observation, perinatal factors as well as parental and environmental factors on
      the children's IQ. MATERIAL AND METHODS: 44 children (28 girls and 16 boys) aged
      3.5-18 years (mean age 7.3+/- 3.5) were enrolled in the study. The subjects'
      mental development was analyzed. General intelligence quotient was measured on
      verbal and non-verbal scale and chosen parameters of mental development were
      measured. The evaluation of mental development was performed in two age groups:
      group A - 20 patients in the age range 3.5-5.9 years (mean age 5.3+/-0.8) tested
      using the Columbus method, and group B - 24 patients in the age range 6-18 years
      (mean age 10.3+/-2.2) tested on the Wechsler Scale. RESULTS: The intelligence
      quotient (IQ) in both groups was within the average IQ range on Wechsler scale.
      Mean IQ values on verbal and non-verbal scale were comparable and within the
      average IQ range on Wechsler scale. The level of intelligence in group A
      correlated, on the brink of statistical significance (IS), with the education
      level of the parents (r=0.32; p=0.0934), while in the group B - IS correlated
      with birth weight (r=0.62; p=0.00247), it correlated on the brink of statistical
      significance with the education level of parents (r=0.4; p=0.0532) and mother's
      age (r=0.41; p=0.0514). The level of intelligence on verbal scale in group B,
      statistically significant, positively correlated with the body mass at birth
      (r=0.62; p=0.00147) and negatively with the mean value of TSH in 2-year follow-up
      period (r=-0.47; p=0.0381). The level of general intelligence and on verbal and
      non-verbal scale did not correlate with the time of commencement of therapy with
      LT4, place of residence or TSH value in the screening test. CONCLUSIONS: 1.
      Mental development of the studied children with CH was within normal range. 2.
      Out of all measured parameters determining mental development, tasks in
      mathematics, analysis and synthesis, visual concentration and concentration on
      the hearing level had worst results. 3. The level of TSH in the screening test
      had no effect on the mental development of children with CH. 4. Out of all
      environmental factors, parental education influenced the mental development of
      the studied children.

PMID- 20813088
TI  - [The role of FTO gene polymorphism in the pathogenesis of obesity].
AB  - Both environmental and genetic factors play a role in the pathogenesis of
      obesity. At present, researchers are examining the genetic background of
      overweight. Over 100 genes are suspected to influence the obesity. One of those
      genes is FTO (fat mass and obesity-associated gene). In the manuscript, the
      relationship between FTO gene polymorphism (AA allele) and overweight, obesity
      and their consequences are discussed. It was proved, in studies on large number
      of people, that FTO gene polymorphism is related to higher body mass index,
      weight and abdominal circumference. Some authors showed that FTO gene
      polymorphism influences the food intake, energy expanditure and insulin
      resistance. The expression of FTO gene product was noticed in both, the
      peripheral as well as central nervous system (hypothalamus). It is possible that
      FTO gene product is involved in the DNA and RNA reparation and other metabolic
      processes, however, its function is not yet clear. The assessment of FTO gene
      polymorphism can allow us to separate patients with the tendency for higher
      weight. The elucidation of the role of FTO in the pathogenesis of obesity can
      result in the development of new therapeutic options for this epidemic of XXI
      century.

PMID- 20813089
TI  - [Endocrine disorders in children after treatment for brain tumors].
AB  - Endocrine dysfunction is one of the most common late effect of anticancer
      treatment. The kind and degree of the disorder depend on tumor location, therapy,
      especially on the dose of radiotherapy, different sensitivity of the hypothalamo
      pituitary axes to irradiation, as well as on the time of treatment. The growth
      hormone secretion axis is the most vulnerable part, and growth disorders occure
      most frequently (after a total dose of >30 Gy); then, after a total dose of 50-60
      Gy: gonadotropin, ACTH deficiency, and, rarely, TSH deficiency. Spinal
      irradiation leads to the height loss and disproportionate growth as well as
      dysfunction of gonads and thyroid gland. Chemotherapy (alkylating agents)
      deteriorates gonadal function. The recognition, good and early diagnosis and
      therapy are important to improve the quality of life of the survivors.

PMID- 20813090
TI  - [The importance of case reports in current pediatric endocrinology and metabolism
      literature--the analysis of publications indexed in Medline in the years 2004
      2009].
AB  - INTRODUCTION: Case reports have been used as an educational tool in medicine for
      a long time, as they are usually the first kind of publications prepared by new
      authors. In compliance with the rules of the EBM, the evidence-based medicine, a
      clinical case report (which describes and analyses the manner of diagnosis and
      treatment) appears at the bottom of the hierarchy of scientific evidences. As a
      result, medical periodicals limit the publishing of case reports. The aim of the
      study is to assess how important case reports are in the modern pediatric
      literature, with special interests in endocrine and metabolic disorders. MATERIAL
      AND METHODS: Searching Medline over the last 5 years (October 2004-October 2009)
      using key words "case report" was performed. The limitations: "human", age "all
      children: 0-18 years" and the kind of publication: "case report" were used. For
      the huge number of publications found, the number and language of the publication
      was analyzed, and the first 100 free full-text publications in field of endocrine
      and metabolic disorders in English (from 2007-2009) were rated depending on the
      kind of case and aim of the publication. RESULTS: A total of 55379 publications
      classified by Pubmed as case reports were found, including 48805 English, 1592
      Spanish, 1538 French, 794 German, 370 Polish, 356 Chinese, 265 Russian and 135
      Italian. The published case reports were more often informative than educational
      in character. The content of the published case reports deals more often with the
      notification of a new mutation, less frequently presentation of an interesting,
      rare, unusual case or a new illness or the description of a novel therapy. Less
      often the published case reports appear to be of educational character or those
      concerning diagnostic problems or treatment failure. CONCLUSION: Case reports
      remain an important contribution to the pediatric literature, mainly fulfilling
      an essential role in providing information about new medical problems. Medical
      literature published in Polish is relatively rich in clinical case reports.
      Publishing a case report in field of endocrinology and metabolism in Pubmed
      indexed journal is considered reasonable in situations where a new medical
      condition is being presented (most often a new mutation), a novel therapy has
      been discovered, the case is interesting or where the publishing of such reports
      fulfils didactic/educational needs.

PMID- 20813091
TI  - A fetal dilated and hypertrophic cardiomyopathy associated with maternal
      gestational diabetes--a case report.
AB  - There is an increased risk of a hypertrophic cardiomyopathy and congenital heart
      defects among newborns of diabetic mothers. We report a case of hypertrophic
      cardiomyopathy preceded with dilated cardiomyopathy in a fetus of a diabetic
      mother. The fetal echocardiography at the 23rd week of gestation revealed signs
      of dilated cardiomyopathy with signs of cardiac failure. Under the
      echocardiographic monitoring the successful treatment was performed. In spite of
      poor prognosis, the child was born at the 39th gestation week in a good
      condition.

PMID- 20813092
TI  - Studies of quinapyramine-resistance of Trypanosoma brucei evansi in China.
AB  - In the present article, we summarize our studies of antrycide-resistance of
      Trypanosoma brucei evansi in four aspects in the last recent several years, the
      analysis of quinapyramine-sensitive situation of T. b. evansi in China,
      biological characteristics of T. b. evansi population in quinapyramine-resistance
      and biological materials of quinapyramine-resistance in T. b. evansi population.
      Firstly, the correlative assays of effective dosage of quinapyramine on T. b.
      evansi disease between in vivo and in vitro methods showed that their
      relationship was parabolic with positive correlation. On the other hand, the
      IC(50) and CD(100) values of 12 T. b. evansi isolates, AHB, GDB1, GDB2, HNB,
      JSB1, JSB2, YNB, ZJB, GDH, GXM, HBM and XJCA, collected from buffaloes, horses,
      mules and camels across nine provinces of China were examined using the two
      methods, respectively. Among them, the nine isolates, AHB, GDB1, GDB2, HNB, JSB1,
      JSB2, YNB, ZJB and GDH, became quinapyramine-sensitive T. b. evansi. Secondly, T.
      evansi populations could rapidly obtain antrycide-resistance when they were
      passed through immunosuppressed mice treated with low doses of the drug. But, the
      replication rate of trypanosomes with antrycide-resistance decreases as the level
      of drug-resistance increases. Thirdly, the analysis of the HK, G6PDH, ALAT and
      ASAT isoenzymes showed that they were not involved in the quinapyramine
      resistance of T. b. evansi. But the protein bands of 15.79kDa and 19.76kDa might
      be involved in the antrycide-resistance of T. b. evansi population. At genetic
      level, the gene, TbTA1, could be amplified from the T. b. evansi isolate
      sensitive to quinapyramine-sensitivity but the T. b. evansi isolate with
      quinapyramine-resistance using not only the RT-PCR technique, but also PCR
      technique. We used the SSH (Suppression Subtractive Hybridization) to clone
      highly or low expressed cDNA fragments caused by production of antrycide
      resistance in T. b. evansi. The 5 low and 9 high expressed new cDNA fragments
      were amplified. Among them, the 3 low expressed cDNA fragments had the same
      sequence of 65 amino acids and the 3 high expressed cDNA fragments were located
      in chromosome VI, like T. brucei. Lastly, more work needs to be done in order to
      elucidate the mechanism of quinapyramine-resistance of T. b. evansi.

PMID- 20813093
TI  - Excited-state properties of the 16kDa red carotenoid protein from Arthrospira
      maxima.
AB  - We have studied spectroscopic properties of the 16kDa red carotenoid protein
      (RCP), which is closely related to the orange carotenoid protein (OCP) from
      cyanobacteria. Both proteins bind the same chromophore, the carotenoid 3'
      hydroxyechinenone (hECN), and the major difference between the two proteins is
      lack of the C-terminal domain in the RCP; this results in exposure of part of the
      carotenoid. The excited-state lifetime of hECN in the RCP is 5.5ps, which is
      markedly longer than in OCP (3.3ps) but close to 6ps obtained for hECN in organic
      solvent. This confirms that the binding of hECN to the C-terminal domain in the
      OCP changes conformation of hECN, thereby altering its excited-state properties.
      Hydrogen bonds between the C-terminal domain and the carotenoid are also absent
      in the RCP. This allows the conformation of hECN in the RCP to be similar to that
      in solution, which results in comparable excited-state properties of hECN in
      solution. The red-shift of the RCP absorption spectrum is most likely due to
      aggregation of RCP induced by hydrophobic nature of hECN that, when exposed to
      buffer, stimulates formation of assemblies minimizing contact of hECN with water.
      We suggest that the loss of the C-terminal domain renders the protein
      amphipathic, containing both hydrophobic (the exposed part of hECN) and
      hydrophilic (N-terminal domain) regions, and may help the RCP to interact with
      lipid membranes; exposed hECN can penetrate into the hydrophobic environment of
      the lipid membrane, possibly to provide additional photoprotection.

PMID- 20813094
TI  - Inhibition of SIRT1 by a small molecule induces apoptosis in breast cancer cells.
AB  - Overexpression of SIRT1, a NAD+-dependent class III histone deacetylases (HDACs),
      is implicated in many cancers and therefore could become a promising antitumor
      target. Here we demonstrate a small molecule SIRT1 inhibitor, ILS-JGB
      1741(JGB1741) with potent inhibitory effects on the proliferation of human
      metastatic breast cancer cells, MDA-MB 231. The molecule has been designed using
      medicinal chemistry approach based on known SIRT1 inhibitor, sirtinol. The
      molecule showed a significant inhibition of SIRT1 activity compared to sirtinol.
      Studies on the antitumor effects of JGB on three different cancer cell lines,
      K562, HepG2 and MDA-MB 231 showed an IC50 of 1, 10 and 0.5 MUM, respectively.
      Further studies on MDA-MB 231 cells showed a dose-dependent increase in K9 and
      K382 acetylation of H3 and p53, respectively. Results also demonstrated that
      JGB1741-induced apoptosis is associated with increase in cytochrome c release,
      modulation in Bax/Bcl2 ratio and cleavage of PARP. Flowcytometric analysis showed
      increased percentage of apoptotic cells, decrease in mitochondrial membrane
      potential and increase in multicaspase activation. In conclusion, the present
      study indicates the potent apoptotic effects of JGB1741 in MDA-MB 231 cells.

PMID- 20813095
TI  - Prevention of in vitro hepatic stellate cells activation by the adenosine
      derivative compound IFC305.
AB  - We have previously shown that adenosine and the aspartate salt of adenosine
      (IFC305) reverse pre-established CCl(4)-induced cirrhosis in rats. However, their
      molecular mechanism of action is not clearly understood. Hepatic stellate cells
      (HSC) play a pivotal role in liver fibrogenesis leading to cirrhosis, mainly
      through their activation, changing from a quiescent adipogenic state to a
      proliferative myofibrogenic condition. Therefore, we decided to investigate the
      effect of IFC305 on primary cultured rat HSC. Our results reveal that this
      compound suppressed the activation of HSC, as demonstrated by the maintenance of
      a quiescent cell morphology, including lipid droplets content, inhibition of
      alpha-smooth muscle actin (alpha-SMA) and collagen alpha1(I) expression, and up
      regulation of MMP-13, Smad7, and PPARgamma expression, three key antifibrogenic
      genes. Furthermore, IFC305 was able to repress the platelet-derived growth factor
      (PDGF)-induced proliferation of HSC. This inhibition was independent of adenosine
      receptors stimulation; instead, IFC305 was incorporated into cells by adenosine
      transporters and converted to AMP by adenosine kinase. On the other hand,
      addition of pyrimidine ribonucleoside as uridine reversed the suppressive effect
      of IFC305 on the proliferation and activation of HSC, suggesting that
      intracellular pyrimidine starvation would be involved in the molecular mechanism
      of action of IFC305. In conclusion, IFC305 inhibits HSC activation and maintains
      their quiescence in vitro; these results could explain in part the antifibrotic
      liver beneficial effect previously described for this compound on the animal
      model.

PMID- 20813096
TI  - Disruption of multidrug and toxin extrusion MATE1 potentiates cisplatin-induced
      nephrotoxicity.
AB  - Multidrug and toxin extrusion 1 (MATE1/SLC47A1) is expressed in the brush-border
      membrane of renal proximal tubules and mediates the efflux of cationic drugs. In
      the present study, the role of MATE1 in the nephrotoxicity of cisplatin was
      investigated in vivo and in vitro. Cisplatin (15mg/kg) was administered
      intraperitoneally to wild-type (Mate1(+/+)) and Mate1 knockout (Mate1(-/-)) mice.
      Lifespan was significantly shorter in Mate1(-/-) mice than Mate1(+/+) mice. Three
      days after the administration of cisplatin, plasma creatinine and blood urea
      nitrogen (BUN) levels were increased in both Mate1(+/+) and Mate1(-/-) mice
      compared with vehicle-treated controls, and creatinine clearance was decreased.
      Moreover, a significant rise in creatinine and BUN levels was observed in
      cisplatin-treated Mate1(-/-) mice in comparison to Mate1(+/+) mice. A
      pharmacokinetic analysis revealed the plasma concentration and renal accumulation
      of cisplatin to be higher in Mate1(-/-) mice than Mate1(+/+) mice 1h after a
      single intravenous administration of cisplatin (0.5mg/kg). Furthermore, the
      combination of a selective MATE inhibitor, pyrimethamine, with cisplatin also
      elevated creatinine and BUN levels compared to cisplatin alone. In experiments in
      vitro, the cellular uptake of cisplatin was stimulated by the expression of mouse
      MATE1 as well as organic cation transporters OCT1 and OCT2. In conclusion, MATE1
      mediates the efflux of cisplatin and is involved in cisplatin-induced
      nephrotoxicity.

PMID- 20813098
TI  - Pharmacological characterization of repeated corticosterone injection-induced
      depression model in rats.
AB  - Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in
      patients with psychotic major depression (PMD), and a higher rate of cortisol
      hypersecretion is observed in PMD than in nonpsychotic patients. Approximately
      19% of patients who meet the criteria for major depressive disorder (MDD) have
      psychotic features. Accumulated studies have indicated that repeated
      corticosterone (CORT) injections induce depressive behavioral and neurochemical
      manifestations in rodents. However, the pharmacological characterization of this
      model has not been fully established. In the present study, we investigated the
      pharmacological characteristics of this model. Rats received CORT injections (20
      mg/kg, subcutaneously), once per day for 21 consecutive days prior to a
      behavioral test. The rats were then tested for depressive behavior using a forced
      swimming test. The repeated CORT injections increased the immobility time in the
      forced swimming test, indicating an increase in depressive-like behavior. An
      acute treatment with a glucocorticoid receptor antagonist, mifepristone,
      counteracted the depressive-like behavior. In contrast, an acute treatment with a
      selective serotonin reuptake inhibitor (SSRI), fluvoxamine, and a tricyclic
      antidepressant (TCA), imipramine, did not have any effect on this condition,
      while a combination of fluvoxamine and risperidone exerted an antidepressant-like
      effect. This observation is of interest in the light of the clinical findings
      that a combination of antidepressants and antipsychotics, but not SSRIs and TCAs,
      is effective for the treatment of patients with PMD. Based on previous findings
      and the present results, this model could be used as an animal model of PMD and
      may be useful for evaluating the antidepressant-like potential of compounds
      targeting the HPA axis.

PMID- 20813099
TI  - Effects of low level of methylmercury on proliferation of cortical progenitor
      cells.
AB  - Methylmercury (MeHg) is a potent environmental neurotoxin that shows toxicity to
      developing central nervous system (CNS), causing brain damage in children even at
      low exposure levels. However, the mechanisms for its effect on CNS are not well
      understood. In current study, primary cultures of progenitor cells from embryonic
      cerebral cortex were used as a model system to study the potential effect and the
      underlying mechanism of MeHg on neural progenitor cells. Results showed that, in
      cultured cortical progenitor cells, 48-h exposure to low-level of MeHg (at 2.5
      nM, 5 nM and 50 nM, respectively) caused G1/S cell cycle arrest in a dose
      dependent manner without inducing cell death. Interestingly, the expression of
      cyclin E, which promotes G1/S transition, but not cyclin D1 and CDK2, was
      selectively downregulated by exposure of MeHg. In addition, low-level of MeHg
      inhibited the maintenance of ERK1/2 phosphorylation, possibly by abolishing the
      late phase ERK1/2 activation induced by bFGF. Thus, MeHg may induce proliferation
      inhibition and cell cycle arrest of neural progenitor cells via regulating cyclin
      E expression and perturbing a pathway that involves ERK1/2.

PMID- 20813097
TI  - Ultrastructural relationship between the mu opioid receptor and its interacting
      protein, GPR177, in striatal neurons.
AB  - GPR177, the mammalian ortholog of Drosophila Wntless/Evi/Sprinter, was recently
      identified as a novel mu-opioid receptor (MOR) interacting protein. GPR177 is a
      trans-membrane protein pivotal to mediating the secretion of Wnt signaling
      proteins. Wnt proteins, in turn, are essential in regulating neuronal
      development, a phenomenon inhibited upon chronic exposure to MOR agonists such as
      morphine and heroin. We previously showed that GPR177 and MOR are co-localized in
      the mouse dorsolateral striatum; however, the nature of this interaction was not
      fully elucidated. Therefore, in the present study, we examined cellular
      substrates for interactions between GPR177 and MOR using a combined immunogold
      silver and peroxidase detection approach in coronal sections in the dorsolateral
      segment of the striatum. Semi-quantitative analysis of the ultrastructural
      distribution of GPR177 and MOR in striatal somata and in dendritic processes
      showed that, of the somata and dendritic processes exhibiting GPR177, 32%
      contained MOR immunolabeling while for profiles exhibiting MOR, 37% also
      contained GPR177 immunoreactivity. GPR177-labeled particles were localized
      predominantly along both the plasma membrane and within the cytoplasm of MOR
      labeled dendrites. Somata and dendritic processes that contained both GPR177 and
      MOR more often received symmetric (inhibitory-type) synapses from unlabeled axon
      terminals. To further define the phenotype of GPR177 and MOR-containing cellular
      profiles, triple immunofluorescence detection showed that GPR177 and MOR are
      localized in neurons containing the opioid peptide, enkephalin, within the
      dorsolateral striatum. The results provide an anatomical substrate for
      interactions between MOR and its interacting protein, GPR177, in striatal opioid
      containing neurons that may underlie the morphological alterations produced in
      neurons by chronic opiate use.

PMID- 20813100
TI  - Chronic treatment with fibrates elevates superoxide dismutase in adult mouse
      brain microvessels.
AB  - Fibrates are activators of peroxisome proliferator-activated receptor (PPAR)
      alpha. Pretreatment with fibrates has been shown to protect brain against
      ischemia in mice. We hypothesized that fibrates elevate superoxide dismutase
      (SOD) levels in the brain microvessels (BMVs). BMVs were isolated from male
      C57BL/6 and PPARalpha null mice that had been treated with fenofibrate or
      gemfibrozil for 7 days. To examine the effect of discontinuation of fenofibrate,
      another animal group treated with fenofibrate was examined on post
      discontinuation day 3 (D-3). To examine whether SOD elevations attenuate
      oxidative stress in the ischemic brain, separate animals treated with fenofibrate
      for 7 days were subjected to 60 minutes of focal ischemia on post-discontinuation
      day 0 (D-0) or D-3. Fenofibrate (30 mg/kg) increased mRNA levels of all three
      isoforms of SOD and activity level in BMV on D-0, but these effects were not
      detected on D-3. The elevations were not detected in PPARalpha null mice. SOD
      levels were also elevated by gemfibrozil (30 mg/kg). Fenofibrate significantly
      reduced superoxide production and protein oxidation in the ischemic brain at 30
      minutes after reperfusion. Fenofibrate reduced infarct size measured at 24 hours
      after reperfusion on D-0; however, the infarct reduction was not seen when
      ischemia was induced on D-3. These findings suggest that fibrates elevate SOD in
      BMV through PPARalpha, which contributes to the infarct reduction, at least in
      part. Further studies are needed to establish the link between the SOD elevations
      and the brain protection by fibrates against ischemia.

PMID- 20813101
TI  - Formation of acetaldehyde-derived DNA adducts due to alcohol exposure.
AB  - Epidemiological studies have identified chronic alcohol consumption as a
      significant risk factor for cancers of the upper aerodigestive tract, including
      the oral cavity, pharynx, larynx and esophagus, and for cancer of the liver.
      Ingested ethanol is mainly oxidized by the enzymes alcohol dehydrogenase (ADH),
      cytochrome P-450 2E1 (CYP2E1), and catalase to form acetaldehyde, which is
      subsequently oxidized by aldehyde dehydrogenase 2 (ALDH2) to produce acetate.
      Polymorphisms of the genes which encode enzymes for ethanol metabolism affect the
      ethanol/acetaldehyde oxidizing capacity. ADH1B*2 allele (ADH1B, one of the enzyme
      in ADH family) is commonly observed in Asian population, has much higher
      enzymatic activity than ADH1B*1 allele. Otherwise, approximately 40% of Japanese
      have single nucleotide polymorphisms (SNPs) of the ALDH2 gene. The ALDH2 *2
      allele encodes a protein with an amino acid change from glutamate to lysine
      (derived from the ALDH2*1 allele) and devoid of enzymatic activity. Neither the
      homozygote (ALDH2*2/*2) nor heterozygote (ALDH2*1/*2) is able to metabolize
      acetaldehyde promptly. Acetaldehyde is a genotoxic compound that reacts with DNA
      to form primarily a Schiff base N(2)-ethylidene-2'-deoxyguanosine (N(2)
      ethylidene-dG) adduct, which may be converted by reducing agents to N(2)-ethyl-2'
      deoxyguanosine (N(2)-ethyl-dG) in vivo, and strongly blocked translesion DNA
      synthesis. Several studies have demonstrated a relationship between ALDH2
      genotypes and the development of certain types of cancer. On the other hand, the
      drinking of alcohol induces the expression of CYP2E1, resulting in an increase in
      reactive oxygen species (ROS) and oxidative DNA damage. This review covers the
      combined effects of alcohol and ALDH2 polymorphisms on cancer risk. Studies show
      that ALDH2*1/*2 heterozygotes who habitually consume alcohol have higher rates of
      cancer than ALDH2*1/*1 homozygotes. Moreover, they support that chronic alcohol
      consumption contributes to formation of various DNA adducts. Although some DNA
      adducts formation is demonstrated to be an initiation step of carcinogenesis, it
      is still unclear that whether these alcohol-related DNA adducts are true factors
      or initiators of cancer. Future studies are needed to better characterize and to
      validate the roles of these DNA adducts in human study.

PMID- 20813102
TI  - "Factory" laboratories: blessed are those who have been persecuted for the sake
      of righteousness, for theirs is the kingdom of heaven.

PMID- 20813103
TI  - PDCD2 is essential for inner cell mass development and embryonic stem cell
      maintenance.
AB  - PDCD2 is a conserved eukaryotic protein implicated in cell cycle regulation by
      virtue of its interactions with HCFC1 and the NCOR1/SIN3A corepressor complex.
      Pdcd2 transcripts are enriched in ES cells and other somatic stem cells, and its
      ortholog is essential for hematopoietic stem cell maintenance in Drosophila. To
      characterize the physiological role(s) of mammalian PDCD2, we created a
      disruption allele in mice. Pdcd2(-/-) embryos underwent implantation but did not
      undergo further development. Inner cell masses (ICMs) from Pdcd2(-/-) blastocysts
      failed to outgrow in vitro. Furthermore, embryonic stem cells (ESCs) require
      PDCD2 as demonstrated by the inability to generate Pdcd2(-/-) ESCs in the absence
      of an ectopic transgene. Upon differentiation of ESCs by retinoic acid treatment
      or LIF deprivation, PDCD2 levels declined. In conjunction with prior studies,
      these results indicate that in vivo, PDCD2 is critical for blastomere and ESC
      maintenance by contributing to the regulation of genes in a manner essential to
      the undifferentiated state of these cells.

PMID- 20813104
TI  - Role of store-operated calcium entry in imperatorin-induced vasodilatation of rat
      small mesenteric artery.
AB  - Store-operated Ca(2+) entry (SOCE) has recently been proposed to contribute to
      Ca(2+) influx in vascular smooth muscle cells (VSMCs). Imperatorin is known for
      its potent vasodilatory effects as a dietary furanocoumarin. The study was
      designed to examine the hypothesis that SOCE have a functional role in
      imperatorin-induced vasodilation. Small mesenteric resistance arteries and
      mesenteric VSMCs were obtained from rats. Isometric tensions of isolated artery
      rings were measured by a sensitive myograph system. Laser scanning confocal
      microscopy was used to determine the intracellular Ca(2+) concentration of fluo-3
      loaded VSMCs. Imperatorin (1-100 MUM) relaxed artery rings precontracted by
      phenylephrine in a concentration-dependent manner. In cultured mesenteric VSMCs,
      passive store depletion by thapsigargin and active store depletion by
      phenylephrine both induced Ca(2+) influx due to SOCE. Imperatorin didn't inhibit
      SOCE-mediated increases in cytosolic Ca(2+) levels evoked by the emptying of the
      stores. In isolated artery rings, imperatorin didn't inhibit SOCE-induced
      contractions due to store depletion. Our results exclude SOCE mechanism of
      vasodilatation by imperatorin. But imperatorin is partly similar with nifedipine
      in vasorelaxation effect.

PMID- 20813105
TI  - Inhibition of nNOS prevents and inhibition of iNOS reverses alpha,beta-meATP
      induced facilitation of neck muscle nociception in mice.
AB  - Infusion of alpha,beta-methylene ATP (alpha,beta-meATP) into murine neck muscle
      facilitates brainstem nociception. Unspecific nitric oxide synthase (NOS)
      inhibition prevents and reverses this sensitization. It is unclear whether
      neuronal (nNOS), inducible (iNOS) or endothelial NOS isoenzymes are involved in
      this alpha,beta-meATP effect. Hypothesized involvement of nNOS isoenzyme was
      addressed by preceding (0.5, 1, and 2 mg/kg) and subsequent (2 mg/kg)
      intraperitoneal injection of the nNOS-inhibitor NPLA. iNOS involvement was
      addressed by subsequent, intraperitoneal administration of the iNOS-inhibitor
      1400 W (2 mg/kg). Brainstem nociception was monitored by the jaw-opening reflex
      elicited via electrical tongue stimulation in 45 anesthetized mice. Preceding
      NPLA dose-dependently prevented alpha,beta-meATP-induced reflex facilitation.
      Whereas subsequent inhibition of nNOS showed no effect, iNOS inhibition by 1400 W
      significantly reversed reflex facilitation. Data provide evidence that nNOS plays
      a major role in induction and iNOS in maintenance of facilitation in neck muscle
      nociception. Divergent roles of NOS isoenzymes may promote research on target
      specific treatment for headache and neck muscle pain.

PMID- 20813106
TI  - Effect of interferon-gamma on inflammatory cytokine-induced bradykinin B1
      receptor expression in human vascular cells.
AB  - The expression of the bradykinin B(1) receptor is strongly regulated in vascular
      tissue following injury, with little or no expression in healthy tissues. The
      present work aimed to verify whether primary human vascular cells (umbilical vein
      endothelial cells, umbilical artery smooth muscle cells) respond to tumor
      necrosis factor (TNF)-alpha and interferon (IFN)-gamma by an upregulation of B(1)
      receptors and whether these pathways interact. B(1) receptor expression was
      quantified using a [(3)H]Lys-des-Arg(9)-bradykinin binding assay (cell surface
      protein) and RT-PCR (mRNA). A pharmacological approach exploiting several
      inhibitory drugs related to cytokine signaling was applied. The combined
      treatment with TNF-alpha and IFN-gamma had a synergistic effect on B(1) receptor
      expression in both cell types, increasing primarily receptor abundance in both
      cell types (16 h) and mRNA concentration (4h) in endothelial cells. The
      synergistic effect of the IFN-gamma-TNF-alpha combination was abated by drugs
      targeted at the signaling of either cytokine (for TNF-alpha: etanercept or the
      IkappaB kinase 2 inhibitor TPCA-1; for IFN-gamma: neutralizing antibodies to IFN
      gamma, a pan-Jak inhibitor but not the Jak2 inhibitor AG490). Thus, Jak2
      signaling may not be recruited by the IFN-gamma receptors in vascular cells;
      however, Stat1 phosphorylation was correlated as expected to the effect of IFN
      gamma on B(1) receptor expression. Random migration was inhibited by the B(1)
      receptor agonist Lys-des-Arg(9)-bradykinin only in smooth muscle cells pretreated
      with the cytokine combination. The amplificatory effect of IFN-gamma on TNF-alpha
      induced bradykinin B(1) receptor expression is relevant to vasculopathies
      associated with T helper 1 cytokines.

PMID- 20813107
TI  - Regression of liver fibrosis by taurine in rats fed alcohol: effects on collagen
      accumulation, selected cytokines and stellate cell activation.
AB  - The antifibrogenic effect of taurine in experimental liver fibrosis has been
      shown. The role of taurine to abate fibrogenic mediators and collagen deposition
      during liver fibrosis induced by simultaneous administration of iron carbonyl
      (0.5% w/w) and alcohol (6 g/kg/day) was investigated in this study. Liver
      histology, the levels of inflammatory cytokines, stellate cell activation,
      oxidative stress and collagen content were assessed. Liver fibrosis and a rise in
      collagen content in ethanol plus iron-fed rat were evident from van Gieson and
      Masson's trichrome staining respectively. Hepatic myeloperoxidase activity and
      plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha)
      were markedly elevated. This was associated with an imbalance in the oxidant
      antioxidant system, increased expression of transforming growth factor-beta(1)
      (TGF-beta(1)) and stellate cell activation suggested by alpha-smooth muscle actin
      (alpha-SMA) localization. This condition was protected in the presence of
      taurine. Taurine lowered the levels of IL-6, TNF-alpha and peroxidation products
      and the expression of alpha-SMA, desmin and TGF-beta(1) and improved the
      antioxidant status. A positive relationship between hepatic collagen with iron
      and lipid peroxides and an inverse relationship between collagen and glutathione
      were noted. It is concluded that taurine reduces iron-potentiated alcoholic liver
      fibrosis by curtailing oxidative stress, production of inflammatory and
      fibrogenic mediators and activation of stellate cells.

PMID- 20813108
TI  - SA14867, a newly synthesized kappa-opioid receptor agonist with antinociceptive
      and antipruritic effects.
AB  - SA14867 ((+)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-ethoxyethyl)-N
      isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline O,O'-diacetyl-L
      tartrate), a selective kappa-opioid receptor agonist, was synthesized and its
      antinociceptive and antipruritic effects were investigated. In a functional
      binding assay, SA14867 showed approximately more than 31,000 and 2200 fold higher
      affinity for the kappa-opioid receptor than for the mu- and delta-opioid
      receptors, respectively. SA14867 inhibited acetic acid-induced writhing and
      formalin test results after oral administration. The ED(50) values of SA14867 for
      acetic acid-induced writhing and for formalin test first phase and second phase
      were 1.9, 9.4, and 6.4 mg/kg, respectively. These values were smaller than those
      of asimadoline, U-50488H, and tramadol. SA14867 also showed antinociceptive
      effects in silver nitrate-induced arthritis that were as strong as U-50488H,
      tramadol, and morphine, and were stronger than asimadoline. The ED(50) value of
      SA14867 for hyperalgesia of arthritis was approximately 10 mg/kg. In addition,
      SA14867 showed antipruritic effects on 5-hydroperoxyeicosatetraenoic acid (HPETE)
      and substance P-induced pruritic models at 1 to 3 mg/kg. SA14867 also attenuated
      scratching reactions in a morphine-induced pruritic model in monkeys. Some of the
      inhibitory effects of SA14867 on nociceptive and pruritic models were attenuated
      by a kappa-opioid receptor antagonist, nor-BNI. These results suggest that
      SA14867 is a potential antinociceptive and antipruritic drug.

PMID- 20813109
TI  - Clusterin induces CXCR4 expression and migration of cardiac progenitor cells.
AB  - Clusterin (CST) is a stress-responding protein with multiple biological
      functions, including the inhibition of apoptosis and inflammation and transport
      of lipids. It may also participate in cell traffic and migration. In the process
      of post-infarct cardiac tissue repair, stem cells migrate into the damaged
      myocardium under the influence of chemoattractive substances such as stromal cell
      derived factor (SDF). This study aimed at testing whether CST enhances expression
      of stem cell homing receptor and migration of cardiac progenitor cells (CPCs).
      CPCs isolated from fetal canine hearts transduced by CST cDNA expressed high
      levels of CXCR4, a receptor for SDF-1. The transfected cells also showed an
      increased migratory response to SDF-1 stimulation. The SDF-1-mediated migration
      of the CST-expressing CPCs was attenuated by PI3 kinase inhibitor LY294002 but
      not by mitogen-activated protein/ERK kinase inhibitor PD98059. Analysis of cell
      cycle by flow cytometry revealed no significant difference in cell cycle between
      the transduced and control CPCs. Thus, CST expression may increase CPCs migration
      via increasing CXCR4 expression and SDF-1/chemokine receptor signaling in a
      PI3/Akt-dependent manner.

PMID- 20813110
TI  - Nitric oxide modulates the expression of endothelial cell adhesion molecules
      involved in angiogenesis and leukocyte recruitment.
AB  - Tumor angiogenesis and immune response have in common to be cell recognition
      mechanisms, which are based on specific adhesion molecules and dependent on
      nitric oxide (NO(*)). The aim of the present study is to deepen the mechanisms of
      angiogenesis and inflammation regulation by NO(*) to find out the molecular
      regulation processes that govern endothelial cell permeability and leukocyte
      transmigration. Effects of NO(*), either exogenous or produced in hypoxic
      conditions, were studied on microvascular endothelial cells from skin and lymph
      node because of their strong involvement in melanoma progression. We found that
      NO(*) down-regulation of pseudo-vessel formation was linked to a decrease in
      endothelial cell ability to adhere to each other which can be explain, in part,
      by the inhibition of PECAM-1/CD31 expression. On the other hand, NO(*) was shown
      to be able to decrease leukocyte adhesion on an endothelial monolayer, performed
      either in static or in rolling conditions, and to modulate differentially CD34,
      ICAM-1/CD54, ICAM-2/CD102 and VCAM-1/CD106 expression. In conclusion, during
      angiogenesis and leukocyte recruitment, NO(*) regulates cell interactions by
      controlling adhesion molecule expression and subsequently cell adhesion.
      Moreover, each endothelial cell type presents its own organospecific response to
      NO(*), reflecting the functions of the tissue they originate from.

PMID- 20813112
TI  - Effects of starvation and parasitism on foregut contraction in larval Manduca
      sexta.
AB  - Larvae of Manduca sexta are parasitised by the braconid wasp, Cotesia congregata.
      In this study we examined whether contraction activity of the semi-isolated
      foregut was affected by parasitism. Parasitised larvae fed significantly less
      compared with unparasitised control larvae, therefore starved unparasitised
      animals were used as controls. Rate and force of foregut contraction in control
      caterpillars significantly increased with days of starvation. However, only
      contraction force in foreguts of parasitised larvae increased over time following
      infection. The presence of food in the foregut of caterpillars starved 7 days
      suggested that food moved anteriorly from the midgut and that contraction became
      antiperistaltic, but only normal peristalsis occurred in parasitised
      caterpillars. Rate and force of gut contractions may be controlled independently
      and starvation did not truly mimic the effects of the parasitoids. Dissection of
      caterpillars with emerged wasps indicated that 47% had a single wasp larva wedged
      between the brain and foregut. Removal of this wasp caused an increased rate of
      foregut contraction of the caterpillar. Brain removal resulted in an increased
      rate of foregut contraction only for unparasitised insects. Sectioning of the
      recurrent nerve temporarily eliminated foregut contraction, but the contraction
      began again in 250 s in parasitised caterpillars prior to wasp emergence,
      compared with over 500 s for unparasitised controls and parasitised caterpillars
      following wasp emergence.

PMID- 20813111
TI  - Measuring topology of low-intensity DNA methylation sites for high-throughput
      assessment of epigenetic drug-induced effects in cancer cells.
AB  - Epigenetic anti-cancer drugs with demethylating effects have shown to alter
      genome organization in mammalian cell nuclei. The interest in the development of
      novel epigenetic drugs has increased the demand for cell-based assays to evaluate
      drug performance in pre-clinical studies. An imaging-based cytometrical approach
      that can measure demethylation effects as changes in the spatial nuclear
      distributions of methylated cytosine and global DNA in cancer cells is introduced
      in this paper. The cells were studied by immunofluorescence with a specific
      antibody against 5-methylcytosine (MeC), and 4,6-diamidino-2-phenylindole (DAPI)
      for delineation of methylated sites and global DNA in nuclei. In the
      preprocessing step the segmentation of nuclei in three-dimensional images (3-D)
      is followed by an automated assessment of nuclear DAPI/MeC patterns to exclude
      dissimilar entities. Next, low-intensity MeC (LIM) and low-intensity DNA (LID)
      sites of similar nuclei are localized and processed to obtain specific nuclear
      density profiles. These profiles sampled at half of the total nuclear volume
      yielded two parameters: LIM(0.5) and LID(0.5). The analysis shows that zebularine
      and 5-azacytidine-the two tested epigenetic drugs introduce changes in the
      spatial distribution of low-intensity DNA and MeC signals. LIM(0.5) and LID(0.5)
      were significantly different (p<0.001) in 5-azacytidine treated (n=660) and
      zebularine treated (n=496) vs. untreated (n=649) DU145 human prostate cancer
      cells. In the latter case the LIM sites were predominantly found at the nuclear
      border, whereas treated populations showed different degrees of increase in LIMs
      towards the interior nuclear space, in which a large portion of heterochromatin
      is located. The cell-by-cell evaluation of changes in the spatial reorganization
      of MeC/DAPI signals revealed that zebularine is a more gentle demethylating agent
      than 5-azacytidine. Measuring changes in the topology of low-intensity sites can
      potentially be a valuable component in the high-throughput assessment of
      demethylation and risk of chromatin reorganization in epigenetic-drug screening
      tasks.

PMID- 20813113
TI  - The evolution and structure prediction of coiled coils across all genomes.
AB  - Coiled coils are alpha-helical interactions found in many natural proteins.
      Various sequence-based coiled-coil predictors are available, but key issues
      remain: oligomeric state and protein-protein interface prediction and extension
      to all genomes. We present SpiriCoil (http://supfam.org/SUPERFAMILY/spiricoil),
      which is based on a novel approach to the coiled-coil prediction problem for
      coiled coils that fall into known superfamilies: hundreds of hidden Markov models
      representing coiled-coil-containing domain families. Using whole domains gives
      the advantage that sequences flanking the coiled coils help. SpiriCoil performs
      at least as well as existing methods at detecting coiled coils and significantly
      advances the state of the art for oligomer state prediction. SpiriCoil has been
      run on over 16 million sequences, including all completely sequenced genomes
      (more than 1200), and a resulting Web interface supplies data downloads,
      alignments, scores, oligomeric state classifications, three-dimensional homology
      models and visualisation. This has allowed, for the first time, a genomewide
      analysis of coiled-coil evolution. We found that coiled coils have arisen
      independently de novo well over a hundred times, and these are observed in 16
      different oligomeric states. Coiled coils in almost all oligomeric states were
      present in the last universal common ancestor of life. The vast majority of
      occasions that individual coiled coils have arisen de novo were before the last
      universal common ancestor of life; we do, however, observe scattered instances
      throughout subsequent evolutionary history, mostly in the formation of the
      eukaryote superkingdom. Coiled coils do not change their oligomeric state over
      evolution and did not evolve from the rearrangement of existing helices in
      proteins; coiled coils were forged in unison with the fold of the whole protein.

PMID- 20813114
TI  - Crystal structure of gamma-hexachlorocyclohexane Dehydrochlorinase LinA from
      Sphingobium japonicum UT26.
AB  - LinA from Sphingobium japonicum UT26 catalyzes two steps of dehydrochlorination
      from gamma hexachlorocyclohexane (HCH) to 1,3,4,6-tetrachloro-1,4-cyclohexadiene
      via gamma-pentachlorocyclohexene. We determined the crystal structure of LinA at
      2.25 A by single anomalous dispersion. LinA exists as a homotrimer, and each
      protomer forms a cone-shaped alpha+beta barrel fold. The C-terminal region of
      LinA is extended to the neighboring subunit, unlike that of scytalone dehydratase
      from Magnaporthe grisea, which is one of the most structurally similar proteins
      identified by the DALI server. The structure we obtained in this study is in open
      form, in which gamma-HCH can enter the active site. There is a hydrophobic cavity
      inside the barrel fold, and the active site is largely surrounded by the side
      chains of K20, L21, V24, D25, W42, L64, F68, C71, H73, V94, L96, I109, F113, and
      R129. H73 was considered to function as a base that abstracts the proton of gamma
      HCH through its interaction with D25. Docking simulations with gamma-HCH and
      gamma-pentachlorocyclohexene suggest that 11 residues (K20, I44, L64, V94, L96,
      I109, A111, F113, A131, C132, and T133) are involved in the binding of these
      compounds and support the degradation mechanism.

PMID- 20813115
TI  - Introduction to the special issue on High Resolution Neuropharmacology.

PMID- 20813116
TI  - Serotonergic modulation of extrapyramidal motor disorders in mice and rats: role
      of striatal 5-HT3 and 5-HT6 receptors.
AB  - Previous studies showed that 5-HT(1A) and 5-HT(2) receptors play an important
      role in controlling the extrapyramidal motor disorders. However, the functions of
      other 5-HT receptor subtypes remain elusive. To elucidate the role of 5-HT
      receptors, specifically of 5-HT(3) ~5-HT(7) subtypes, in modifying antipsychotic-
      induced extrapyramidal side effects (EPS), we studied the effects of the 5-HT
      stimulant 5-hydroxytryptophan (5-HTP) and various 5-HT receptor antagonists on
      haloperidol (HAL)-induced bradykinesia and catalepsy in mice and rats.
      Pretreatment of mice with 5-HTP (25-100mg/kg, i.p.) dose-dependently enhanced HAL
      (0.3mg/kg, i.p.)-induced bradykinesia and catalepsy. The potentiation of HAL
      induced EPS by 5-HTP (50mg/kg, i.p.) was significantly inhibited by ritanserin (5
      HT(2) antagonist, 0.3-3mg/kg, i.p.), ondansetron (5-HT(3) antagonist, 0.1-1mg/kg,
      i.p.), or SB-258585 (5-HT(6) antagonist, 1-10mg/kg, i.p.) in a dose-dependent
      manner. However, neither WAY-100135 (5-HT(1A) antagonist, 1-10mg/kg, i.p.), GR
      125487 (5-HT(4) antagonist, 1-10mg/kg, i.p.), SB-699551 (5-HT(5A) antagonist, 1
      10mg/kg, i.p.) nor SB-269970 (5-HT(7) antagonist, 1-10mg/kg, i.p.) reduced the 5
      HTP and HAL-induced bradykinesia or catalepsy. In addition, both ondansetron (0.1
      1mg/kg, i.p.) and SB-258585 (3 and 10mg/kg, i.p.) also alleviated bradykinesia
      and catalepsy induced by HAL (0.5mg/kg, i.p.) alone in mice. Furthermore,
      bilateral microinjection of ondansetron (5 MUg (13.7 nmol) per side) or SB-258585
      (5 MUg (8.92 nmol) per side) into the dorsolateral striatum (dlST) attenuated
      haloperidol-induced catalepsy in rats. These results suggest that serotonergic
      stimulation augments extrapyramidal motor disorders by activating the striatal 5
      HT(3) and 5-HT(6) receptors and the antagonism of these receptors effectively
      alleviates antipsychotic-induced EPS.

PMID- 20813117
TI  - Neuroprotective effect of flurbiprofen in focal cerebral ischemia: the possible
      role of ASIC1a.
AB  - The intracellular calcium overload resulting from glutamate excitotoxicity is
      considered major determinant for neuronal loss during cerebral ischemia.
      Moreover, acidosis mediated ASIC1a activation has also shown to promote
      intracellular calcium overload following ischemic insult. Interestingly, ASIC1a
      was found to be inhibited by NSAIDs particularly flurbiprofen and ibuprofen,
      which could be exploited in hypoxic conditions like cerebral ischemia. This
      prompted us to investigate neuroprotective effect of flurbiprofen, besides its
      possible downstream signaling mechanism in rodent model of focal cerebral
      ischemia. The flurbiprofen treatment, 30 min prior to ischemia and 4 h post
      reperfusion, afforded significant neuroprotection from ischemic injury as
      evidenced by reduction in cerebral infarct volume and neurobehavioral deficit.
      Further, an early calcium dependent rise in levels of nitrite and MDA was also
      found to be significantly (P < 0.01) reduced in ischemic brain regions following
      flurbiprofen pretreatment. It also reduced the proteolytic products (SBDPs)
      caused by ischemic activation of calcium dependent protease calpain. In addition,
      the ex-vivo studies with flurbiprofen in rat brain synaptoneurosomes inhibited
      the acid mediated rise in intracellular calcium levels. These studies thus
      provide neuroprotective profile of flurbiprofen in focal cerebral ischemia with
      its selective effect on ASIC1a.

PMID- 20813118
TI  - Perceived social support moderates the link between threat-related amygdala
      reactivity and trait anxiety.
AB  - Several lines of research have illustrated that negative environments can
      precipitate psychopathology, particularly in the context of relatively increased
      biological risk, while social resources can buffer the effects of these
      environments. However, little research has examined how social resources might
      buffer proximal biological risk for psychopathology or the neurobiological
      pathways through which such buffering may be mediated. Here we report that the
      expression of trait anxiety as a function of threat-related amygdala reactivity
      is moderated by perceived social support, a resource for coping with adversity. A
      significant positive correlation between amygdala reactivity and trait anxiety
      was evident in individuals reporting below average levels of support but not in
      those reporting average or above average levels. These results were consistent
      across multiple measures of trait anxiety and were specific to anxiety in that
      they did not extend to measures of broad negative or positive affect. Our
      findings illuminate a biological pathway, namely moderation of amygdala-related
      anxiety, through which social support may confer resilience to psychopathology.
      Moreover, our results indicate that links between neural reactivity and behavior
      are not static but rather may be contingent on social resources.

PMID- 20813119
TI  - Lack of developmental improvement on a face memory task during adolescence in
      autism.
AB  - Autism Spectrum Disorders (ASD) are associated with abnormalities in face memory,
      which evidence suggests has a protracted development through adolescence. The
      development of face memory in people with and without ASD, from 9 to 29 years
      old, was examined using the Cambridge Face Memory Test (CFMT). Results indicate
      that the developmental improvement evident from adolescence to adulthood
      typically was not apparent in individuals with ASD. While children and
      adolescents with ASD performed similarly to typically developing individuals
      comparable in age and IQ, adults with ASD displayed limitations on the CFMT. The
      pattern of performance was constant across conditions despite differences in the
      timing of the presentation and delay. This atypical development in ASD is
      consistent with the view that the processing of complex visual stimuli continues
      to develop through adolescence, along with the function and structure of the
      temporal lobes, but that this process is disrupted in ASD. This result
      underscores the importance of characterizing adolescent development for
      understanding ASD, and suggests additional opportunities for intervention.

PMID- 20813120
TI  - Diagnostic performance of salivary cortisol and serum osteocalcin measurements in
      patients with overt and subclinical Cushing's syndrome.
AB  - OBJECTIVE: The cut-off value for salivary cortisol measurement for the diagnosis
      of Cushing's syndrome (CS) may depend both on the severity of the disease and the
      composition of control group. Therefore, we examined the utility of midnight
      salivary cortisol measurements in patients who were evaluated for signs and
      symptoms of CS or because they had adrenal incidentalomas. Because serum
      osteocalcin (OC) is considered as a sensitive marker of hypercortisolism, we also
      investigated whether OC could have a role in the diagnosis of CS. PATIENTS AND
      METHODS: Each of the 151 patients was included into one of the following groups:
      (A) overt CS (n=23), (B) subclinical CS (n=18), (C) inactive adrenal adenomas
      (n=40), (D) patients without HPA disturbances (n=70). Patients (C+D) were used as
      controls. Serum, salivary and urinary cortisol, and OC were measured by
      electrochemiluminescence immunoassay. RESULTS: Group A had suppressed OC as
      compared to both group B and group (C+D). Serum and salivary cortisol
      concentrations showed strong negative correlations with OC in patients with overt
      CS. The areas under the curves of salivary and serum cortisol at 24:00 h (0.9790
      and 0.9940, respectively) serum cortisol after low dose dexamethasone test
      (0.9930) and OC (0.9220) obtained from ROC analysis for the diagnosis of overt CS
      were not statistically different. CONCLUSION: This study confirms the usefulness
      of midnight salivary cortisol measurements in the diagnosis of overt CS in the
      everyday endocrinological praxis. Our results suggest that OC may have a role in
      the diagnosis of overt CS.

PMID- 20813121
TI  - Expression in Pichia pastoris and characterization of APETx2, a specific
      inhibitor of acid sensing ion channel 3.
AB  - Acid sensing ion channels (ASICs) are family of proteins predominantly present in
      the central and peripheral nervous system. They are known to play important roles
      in the pathophysiology of pain and ischemic stroke. APETx2 is a potent and
      selective inhibitor of ASIC3-containing channels and was isolated from sea
      anemone Anthopleura elegantissima. To facilitate the study on the molecular
      determinants of ASIC3-ligand interactions, we expressed recombinant APETx2 in the
      Pichia pastoris (P. pastoris) expression system and purified it to homogeneity.
      Recombinant APETx2 produced in P. pastoris inhibited the acid-evoked ASIC3
      current with the IC(50) value of 37.3 nM. The potency of recombinant toxin is
      similar to that of native APETx2. The sequential assignment and structure
      analysis of APETx2 were obtained by 2D and 3D (15)N-edited NMR spectra. Our NMR
      data suggests that APETx2 produced in P. pastoris retained its native fold. The
      results presented here provide the first direct evidence that highly disulfide
      bonded peptide inhibitor of ASIC3, APETx2, can be expressed in P. pastoris with
      correct fold and high yield. We also showed that the R17A mutant exhibited a
      decrease in activity, suggesting the feasibility of the use of this expression
      system to study the interactions between APETx2 and ASIC3. These evidences may
      serve as the basis for understanding the selectivity and activity of APETx2.

PMID- 20813122
TI  - Infant death after nose-horned viper (Vipera ammodytes ammodytes) bite in
      Croatia: A case report.
AB  - A case of a 45-day-old male infant, bitten on the neck by nose-horned viper
      (Vipera ammodytes ammodytes), is reported. This episode occurred while the baby
      was on a picnic with his parents in a hill near a town in southern Croatia. In
      spite of immediate arrival at hospital, where antivenom was administrated and all
      the necessary treatment measures were carried out, the infant died 6 h following
      the bite. The cause of death was severe and progressive hyperkalaemia, massive
      intravascular haemolysis, severe coagulopathy and myocardial dysfunction.

PMID- 20813124
TI  - High-affinity Na(+)-dependent dicarboxylate cotransporter promotes cellular
      senescence by inhibiting SIRT1.
AB  - High-affinity Na(+)-dependent dicarboxylate cotransporter (NaDC3) can transport
      Krebs cycle intermediates into cells. Our previous study has shown that NaDC3
      promotes cellular senescence, but its mechanism is not clear. It is known that
      when the concentration of intermediates in Krebs cycle is increased, NAD(+)/NADH
      ratio will be decreased. NAD(+)-dependent histone deacetylase sirtuin1 (SIRT1)
      prolongs mammalian cellular lifespan. Therefore, we propose that NaDC3
      accelerates cellular aging by inhibiting SIRT1. After NaDC3 was overexpressed in
      two human embryo lung fibroblastic cell lines, WI38 and MRC-5, we found that the
      cells displayed aging-related phenotypes in advance. Meanwhile, the level of
      SIRT1 activity was down-regulated. In WI38/hNaDC3 cells treated with the
      activators of SIRT1, aging-related phenotypes induced by NaDC3 were obviously
      improved. The NAD(+)/NADH ratio in WI38/hNaDC3 cells was also decreased. Further
      study found that enhanced intracellular NAD(+) level could attenuate the aging
      phenotypes induced by NaDC3. Thus, NaDC3 promotes cellular senescence probably by
      inhibiting NAD(+)-dependent SIRT1.

PMID- 20813123
TI  - The impact of intraocular pressure reduction on retinal ganglion cell function
      measured using pattern electroretinogram in eyes receiving latanoprost 0.005%
      versus placebo.
AB  - PURPOSE: To evaluate the impact of intraocular (IOP) reduction on retinal
      ganglion cell (RGC) function measured using pattern electroretinogram optimized
      for glaucoma (PERGLA) in glaucoma suspect and glaucomatous eyes receiving
      latanoprost 0.005% versus placebo. METHODS: This was a prospective, placebo
      controlled, double masked, cross-over clinical trial. One randomly selected eye
      of each subject meeting eligibility criteria was enrolled. At each visit,
      subjects underwent five diurnal measurements between 8:00 am and 4:00 pm
      consisting of Goldmann IOP, and PERGLA measurements. A baseline examination was
      performed following a 4-week washout period, and repeat examination after
      randomly receiving latanoprost or placebo for 4-weeks. Subjects were then crossed
      over to receive the alternative therapy for 4 weeks following a second washout
      period, and underwent repeat examination. Linear mixed-effect models were used
      for the analysis. RESULTS: Sixty-eight eyes (35 glaucoma, 33 glaucoma suspect) of
      68 patients (mean age 67.4 +/- 10.6 years) were enrolled. The mean IOP (mmHg)
      after latanoprost 0.005% therapy (14.9 +/- 3.8) was significantly lower than
      baseline (18.8 +/- 4.7, p<0.001) or placebo (18.0 +/- 4.3), with a mean reduction
      of -20 +/- 13%. Mean PERGLA amplitude (MUV) and phase (pi-radian) using
      latanoprost (0.49 +/- 0.22 and 1.71 +/- 0.22, respectively) were similar (p >
      0.05) to baseline (0.49 +/- 0.24 and 1.69 +/- 0.19) and placebo (0.50 +/- 0.24
      and 1.72 +/- 0.23). No significant (p > 0.05) diurnal variation in PERGLA
      amplitude was observed at baseline, or using latanoprost or placebo. Treatment
      with latanoprost, time of day, and IOP were not significantly (p > 0.05)
      associated with PERGLA amplitude or phase. CONCLUSION: Twenty percent IOP
      reduction using latanoprost monotherapy is not associated with improvement in RGC
      function measured with PERGLA.

PMID- 20813125
TI  - Imaging recognition events between human IgG and rat anti-human IgG by atomic
      force microscopy.
AB  - Chemically immobilized rat anti-human immunoglobulin (IgG) monolayers on thiols
      modified gold substrates were fabricated using self-assembled monolayer (SAM)
      method. The antibody monolayers were imaged before and after free human IgG
      treated, whilst recognition events between antigen and antibody were monitored by
      contact mode atomic force microscopy (CM-AFM) and tapping mode AFM (TM-AFM), with
      topographic and/or phase images being recorded. The obtained images with
      different surface compositions show distinct nanostructures, indicating
      occurrence of recognition and binding events of antigen-antibody. The size of the
      observed surface structures of the antibody monolayer, when tip broaden effect
      had been taken into account, was very close to the actual size of the antibody
      molecule. Thus, these results suggest CM-AFM is capable of, and proven
      satisfactory in detecting protein-protein interactions (PPIs), providing the
      sample was prepared appropriately and the scanning parameters were set
      adequately. Moreover, phase imaging can serve as a real time contrast enhancement
      technique to TM-AFM in terms of highlighting edges and clearly observing fine
      features.

PMID- 20813126
TI  - Chemical characterization of Lycium barbarum polysaccharides and their reducing
      myocardial injury in ischemia/reperfusion of rat heart.
AB  - Polysaccharides were extracted from Lycium barbarum fruits in this work. Fourier
      transform infrared spectroscopy (FT-IR) and high-performance liquid
      chromatography (HPLC) have been employed to characterize this polysaccharides in
      the present study. The results of chemical composition indicated that the L.
      barbarum polysaccharides were composed of two kinds of monosaccharides, namely
      glucose and fructose in molar ratios of 1:2.1. The results indicated that the
      glucose and fructose were the predominant monosaccharides. IR spectrum of L.
      barbarum polysaccharides revealed a typical peaks of polysaccharides. The results
      still showed that L. barbarum polysaccharides significantly decreased the
      myocardium LD level, increased Na(+)-K(+)-ATPase and Ca(2+)-ATPase activities in
      heart ischemia reperfusion (IR) rats. In addition, L. barbarum polysaccharides
      still markedly decreased myocardium Bax positive rate and myocardial cell
      apoptosis and increased Bcl-2 positive rate in a dose-dependent manner. It may be
      concluded that administration of L. barbarum polysaccharides can prevented the
      development of cardiovascular diseases.

PMID- 20813127
TI  - Salmonid Tollip and MyD88 factors can functionally replace their mammalian
      orthologues in TLR-mediated trout SAA promoter activation.
AB  - Many functional details of the piscine Toll-like receptor (TLR) signal-mediated
      activation of immune defense are still elusive. We used an established
      reconstitution system of mammalian TLR signaling to examine if this system would
      allow for pathogen-dependent promoter activation of the serum amyloid A (SAA)
      encoding gene from rainbow trout (Oncorhynchus mykiss) and if the key mediators
      MyD88 and Tollip from trout can functionally substitute for their mammalian
      orthologues. Cells of the established human embryonic kidney line HEK-293 were
      transiently co-transfected with vectors expressing bovine TLR2 or TLR4 factors
      and a reporter gene driven by the promoter of the trout SAA gene. Escherichia
      coli stimulation increased reporter gene expression more than 3-fold. Deletion
      series and point mutations identified in the proximal SAA promoter a composite
      overlapping binding site for NF-kappaB and CEBP factors as crucial for promoter
      activation. Overexpression of NF-kappaB p65, but not of p50 or different members
      of the CEBP factor family proved this factor as an essential driver for SAA
      expression. Overexpression of a transdominant-negative mutant of the trout MyD88
      factor reduced TLR-mediated SAA promoter activation confirming functional
      conservation of its TIR domain. Overexpression of the Tollip factor from trout
      also quenched TLR-mediated NF-kappaB and TLR4-mediated SAA promoter activation.
      The MyD88 mutant and Tollip expression studies confirm the functional homology of
      both piscine factors and their mammalian counterparts. We provide for the first
      time evidence that also the Tollip-mediated negative loop of TLR signaling may be
      conserved in non-mammalian organisms.

PMID- 20813128
TI  - Perforin-dependent cytotoxic mechanism in killing by CD8 positive T cells in
      ginbuna crucian carp, Carassius auratus langsdorfii.
AB  - T cell-mediated cytotoxicity occurs via pathways based on perforin or Fas
      mechanisms. Perforin is a protein present in the cytoplasmic granules of CD8(+)
      cytotoxic T lymphocytes and is secreted to form pores on target cell membranes.
      In fish, although the involvement of perforin in cytotoxicity have been suggested
      for several species, perforin-mediated cytotoxicity of CD8alpha(+) lymphocyte in
      conjunction with expression of the perforin gene has not been reported. In order
      to investigate the killing mechanism of CD8alpha(+) lymphocytes by perforin
      mediated pathway in fish, we measured apoptosis of target cells triggered by
      CD8alpha(+) lymphocytes, performed cytotoxic assays in the presence or absence of
      perforin inhibitor; concanamycin A and EGTA, and analysed the expression of
      perforin1, perforin2 and perforin3 isotypic genes in ginbuna crucian carp. In the
      present study, we found that CTLs attached with target cells. CTL should have
      direct contact with target cells to kill them. Approximately 50% of target cells
      were positive for annexin V after co-cultured with CD8alpha(+) lymphocytes,
      indicating the induction of apoptotic cell death. Concanamycin A, which induces
      depolymerization of perforin resulting in lytic function, suppressed the
      cytotoxicity of CD8alpha(+) cells in a dose-dependent manner. In addition,
      cytotoxicity mediated by CD8alpha(+) lymphocytes were significantly suppressed by
      the addition of the Ca(2+)-chelating agents EGTA or EGTA-Mg(2+), and the addition
      of Ca(2+) restored the killing mechanism of target cells. We further found
      enhanced expression of perforin1 but not perforin2 or perforin3 in CTLs from allo
      sensitized fish. The present study has demonstrated that ginbuna CTLs kill target
      cells through perforin-mediated pathway, suggesting that perforin-mediated
      pathway is conserved throughout vertebrate.

PMID- 20813129
TI  - A multidomain galectin involved in innate immune response of pearl oyster
      Pinctada fucata.
AB  - Galectins could specifically bind to beta-galactoside residues and play crucial
      roles in innate immune responses of vertebrates and invertebrates. In this study,
      the cDNA of a galectin with multiple carbohydrate-recognition domains (CRDs) was
      cloned from pearl oyster Pinctada fucata (designated as PoGal). PoGal cDNA was
      2138bp long and consisted of a 5'-untranslated region (UTR) of 120bp, a 3'-UTR of
      350bp with two cytokine RNA instability motifs (ATTTA), and an open reading frame
      (ORF) of 1668bp encoding a polypeptide of 555 amino acids with an estimated
      molecular mass of 63.4kDa and a theoretical isoelectric point of 4.8. PoGal
      contained four CRDs, each CRD of PoGal all had the conserved carbohydrate-binding
      motifs H-NPR and WG-ER. PoGal shared 43.7% and 62.9% identity to those of bay
      scallop and eastern oyster, respectively, which were only two galectins with four
      CRDs. The phylogenetic analysis revealed that all galectins with four CRDs formed
      a single clade. PoGal mRNA was constitutively expressed in all detected tissues,
      and the expression level of PoGal mRNA was significantly up-regulated in
      digestive gland, mantle, haemocyte, gonad and intestine after Vibrio
      alginolyticus stimulation. The expression profile analysis showed that the
      expression level of PoGal mRNA was significantly up-regulated at 4, 8 and 12h
      after V. alginolyticus stimulation. These results suggested that PoGal was a
      constitutive and inducible acute-phase protein that perhaps involved in innate
      immune response of pearl oyster.

PMID- 20813130
TI  - A large outbreak of Listeria monocytogenes infection with short incubation period
      in a tertiary care hospital.
AB  - OBJECTIVES: Listeria monocytogenes is a foodborne pathogen with a high mortality
      rate. We report a large, nosocomial outbreak of Listeria monocytogenes infection.
      METHODS: Patients with L. monocytogenes isolated from a sterile site, or from
      faeces when diarrhoea and fever were present, were included. Clinical data were
      collected from the patient records. The incubation period was calculated as the
      time between exposure and start of symptoms. RESULTS: Seventeen patients (11
      women, median age 64 years) were infected of whom 15 patients were at increased
      risk for listeriosis. Eleven patients received empiric antibiotic treatment,
      eight of them with cephalosporins. Three patients died with a resulting mortality
      rate of 18%. The source of the outbreak was a Camembert cheese made from
      pasteurised milk containing up to 360 million colony forming units per portion.
      The median incubation period was 3-4 days. CONCLUSIONS: The incubation period in
      this outbreak was significantly shorter than previously reported, a fact that may
      be due to the high number of ingested bacteria. Furthermore, food restrictions in
      hospitals seem warranted, as do treatment with antibiotics effective against L.
      monocytogenes in at-risk populations.

PMID- 20813131
TI  - The roles of TNF in brain dysfunction and disease.
AB  - Certain cytokines, the prototype being the highly pleiotropic TNF, have many
      homeostatic physiological roles, are involved in innate immunity, and cause
      inflammation when in excess. These cytokines have long been accepted to have
      central roles in the pathogenesis of systemic or local non-cerebral disease
      states, whether acute or chronic, and whether or not caused by infectious agents.
      Over the last decade they have also been appreciated to be broadly important in
      brain physiology. As in other organs, excessive levels in brain are harmful, and
      its physiological complexity leads to correspondingly complex dysfunction. This
      review summarizes the burgeoning literature on this topic, and how the functions
      of these molecules, particularly TNF, are influencing the outlook of researchers
      on the pathophysiology of these diseases. Basic brain physiology is thus
      informing knowledge of the brain dysfunction that characterizes such apparently
      diverse states as Alzheimer's disease, trauma (mostly, but not only, to the
      brain), Parkinson's disease, and severe systemic infectious states, including
      malaria, sepsis, viral diseases and major depression. The implication is that the
      anti-cytokine therapies now in use, typically directed at TNF, warrant testing in
      these diseases in circumstances in which the therapeutic agent enters the
      cerebrospinal fluid. Routinely administering such drugs to patients exhibiting
      the neurological changes discussed in this review would simply add another organ
      system to what is already a very successful strategy in the treatment of
      inflammatory disease at other sites, such as joints, skin and gut. Clearly, the
      most relevant research is focussed on Alzheimer's disease, but the principles may
      also apply to other encephalopathies.

PMID- 20813133
TI  - Development of a loop-mediated isothermal amplification assay for rapid and
      sensitive detection of ostreid herpesvirus 1 DNA.
AB  - A loop-mediated isothermal amplification (LAMP) assay was developed for rapid,
      specific and sensitive detection of ostreid herpesvirus 1 (OsHV-1) DNA. A set of
      four primers was designed, based on the sequence of the ATPase subunit of the
      OsHV-1 DNA-packaging terminase gene. The reaction temperature and time were
      optimized to 64 degrees C and 60min, respectively. LAMP products were detected by
      agarose gel electrophoresis or by visual inspection of a color change due to
      addition of fluorescent dye. The developed method was highly specific for
      detection of OsHV-1, and no cross-reaction was observed with other DNA viruses,
      such as White spot syndrome virus (WSSV), Penaeus stylirostris densovirus
      (PstDNV), Turbot reddish body iridovirus (TRBIV) and Lymphocystis disease virus
      (LCDV) found commonly in China. The lower detection limit of the LAMP assay was
      approximately 20 copies per reaction, and it was 100 times more sensitive than
      that of conventional PCR. A comparative evaluation of 10 oyster samples using
      LAMP and PCR assays showed overall correlation in positive and negative results
      for OsHV-1. These results indicate that the LAMP assay is a simple, rapid,
      sensitive, specific and reliable technique for the detection of OsHV-1. The LAMP
      technique has capacity for use for the detection of OsHV-1 both in the laboratory
      and on farms.

PMID- 20813132
TI  - Ketamine-xylazine anesthesia causes hyperopic refractive shift in mice.
AB  - Mice have increasingly been used as a model for studies of myopia. The key to
      successful use of mice for myopia research is the ability to obtain accurate
      measurements of refractive status of their eyes. In order to obtain accurate
      measurements of refractive errors in mice, the refraction needs to be performed
      along the optical axis of the eye. This represents a particular challenge,
      because mice are very difficult to immobilize. Recently, ketamine-xylazine
      anesthesia has been used to immobilize mice before measuring refractive errors,
      in combination with tropicamide ophthalmic solution to induce mydriasis. Although
      these drugs have increasingly been used while refracting mice, their effects on
      the refractive state of the mouse eye have not yet been investigated. Therefore,
      we have analyzed the effects of tropicamide eye drops and ketamine-xylazine
      anesthesia on refraction in P40 C57BL/6J mice. We have also explored two
      alternative methods to immobilize mice, i.e. the use of a restraining platform
      and pentobarbital anesthesia. We found that tropicamide caused a very small, but
      statistically significant, hyperopic shift in refraction. Pentobarbital did not
      have any substantial effect on refractive status, whereas ketamine-xylazine
      caused a large and highly significant hyperopic shift in refraction. We also
      found that the use of a restraining platform represents good alternative for
      immobilization of mice prior to refraction. Thus, our data suggest that ketamine
      xylazine anesthesia should be avoided in studies of refractive development in
      mice and underscore the importance of providing appropriate experimental
      conditions when measuring refractive errors in mice.

PMID- 20813134
TI  - Rapid detection of peste des petits ruminants virus by a reverse transcription
      loop-mediated isothermal amplification assay.
AB  - Peste des petits ruminants virus (PPRV) is the causative agent of peste des
      petits ruminants (PPR), an economically important viral disease of small
      ruminants. In this report, a one-step, single-tube, reverse transcription loop
      mediated isothermal amplification (RT-LAMP) assay was developed for the detection
      of PPRV. A set of six LAMP primers were designed based on the matrix gene
      sequence of PPRV to amplify the target RNA by incubation at 63 degrees C for
      60min with Bst DNA polymerase and reverse transcriptase. The amplified products
      could be observed by the naked eye. The specificity of the RT-LAMP assay was
      validated by amplifying eight strains of PPRV isolated in different geographical
      areas. No cross-reactivity with other related viruses, including rinderpest
      virus, canine distemper virus and measles virus, was detected. The sensitivity of
      the assay was similar to that of real-time reverse transcription polymerase chain
      reaction (RT-PCR) and 10-fold higher than that of conventional RT-PCR. Twenty
      clinical samples were evaluated by the RT-LAMP assay, and the results were
      consistent with those of real-time RT-PCR. As a simple, rapid and accurate
      detection method, this RT-LAMP assay has important potential applications in the
      clinical diagnosis of PPR and the surveillance of PPRV.

PMID- 20813135
TI  - A new strategy for generating geminivirus resistant plants using a DNA
      betasatellite/split barnase construct.
AB  - The betasatellite DNA associated with cotton leaf curl disease contains a single
      ORF, betaC1, which is a pathogenicity determinant. Deletion of the betaC1 ORF
      showed that it was not required for betasatellite replication in the presence of
      Tomato leaf curl virus-Australia (TLCV-Au). A series of betasatellite/split
      mutant barnase gene constructs, in which a direct repeat of the Bacillus
      amyloliquefaciens barnase gene flanked the betasatellite, were shown to replicate
      in tobacco in the presence of TLCV-Au. A betasatellite/split intact barnase gene
      construct, with the optimal direct repeat unit of the barnase gene, was
      introduced into Nicotiana tabacum plants. Approximately one third of the
      transgenic lines containing the betasatellite/split barnase gene constructs were
      shown to be completely resistant to the TLCV-Au infection. The
      betasatellite/split intact barnase gene cassette ensures that there is no
      expression of the barnase in the absence of TLCV-Au, but upon infection of the
      cell with the virus, release of the betasatellite/split barnase cassette as a
      replicating molecule resulting in the reconstitution and expression of an active
      barnase gene and the destruction of the infected cell. This system offers the
      potential to provide resistance in a variety of plant species against
      geminiviruses that support the replication of betasatellite.

PMID- 20813136
TI  - MAP kinase activation increases BK polyomavirus replication and facilitates viral
      propagation in vitro.
AB  - BK polyomavirus causes disease in immunosuppressed patients. BK virus replication
      was augmented in HEL-299 cells cultured in conditions that activated the MAP
      kinase, ERK1/2. To determine if MAP kinase activation increased BK virus
      replication, cells were treated with serum and phorbol 12-myristate 13-acetate
      (PMA). Serum and PMA stimulated large T-antigen expression and increased BK virus
      DNA replication. The effects of serum/PMA were directly related to MAP kinase
      signal activation since viral replication was reduced by the MEK1/2 inhibitor
      U0126. PMA also increased cyclin D1 expression and inhibition of cyclin D1/CDK4
      complex and the cell cycle reduced BK virus infection. The PMA effect occurred
      independent of direct transcriptional activation of the viral NCCR. In HEL-299
      cells, virus infection in high serum and PMA accelerated viral replication that
      resulted, within 7 days, in the production of high titer infectious BK virus.
      These results show that MAP kinase signal activation increases BK virus
      replication.

PMID- 20813138
TI  - Effects of d-amphetamine on short- and long-term memory in spontaneously
      hypertensive, Wistar-Kyoto and Sprague-Dawley rats.
AB  - Diverse studies indicate that the attention deficit hyperactivity disorder (ADHD)
      is associated with alterations in encoding processes, including working or short
      term memory. Some ADHD dysfunctional domains are reflected in the spontaneously
      hypertensive rat (SHR). Here SHR-saline group showed significantly poor STM and
      LTM relative to SD and WKY saline rats. SD and WKY rats treated with d
      amphetamine displayed better STM and LTM, compared to SD-vehicle, WKY-vehicle or
      SHR-d-amphetamine groups.

PMID- 20813137
TI  - Ligand-induced changes in hepatitis C virus NS5B polymerase structure.
AB  - Hepatitis C virus (HCV) RNA-dependent RNA polymerase (NS5B) is required for viral
      replication. Crystal structures of the NS5B apoprotein show that the finger and
      thumb domains interact to encircle the active site, and that inhibitors defined
      by P495 resistance that bind to the thumb-finger interface displace the Delta1
      finger loop and disrupt this structure. Since crystal structures may not reveal
      all of the conformations of a protein in solution we have developed an
      alternative method, using limited trypsin protease digestion, to investigate the
      impact of inhibitors as well as substrates on the movement of the Delta1 loop.
      This assay can be used to study NS5B under conditions that support enzymatic
      activity. In the absence of inhibitors, no specific region of NS5B was
      hypersensitive to trypsin, and no specific intermediate cleavage products were
      formed. Binding of P495-site inhibitors to NS5B induced specific trypsin
      hypersensitivity at lysine residues 50 and 51. Previously characterized
      inhibitors and mutant polymerases were used to link this specific trypsin
      hypersensitivity to movement of the Delta1 loop. Trypsin hypersensitivity
      identical to the inhibitor pattern was also induced by the binding of the RNA
      template. The addition of primer to the NS5B-template complex eliminated the
      hypersensitivity. The data are consistent with displacement of the Delta1 finger
      loop from the thumb by the binding of template, and reversal by the addition of
      primer or NTP. Our results complement inhibitor-enzyme co-crystal studies, and
      the assay provides a rapid and sensitive method to study dynamic changes in HCV
      NS5B polymerase conformation under conditions that support functional activity.

PMID- 20813139
TI  - Sex-dependent behavioral effects of Mthfr deficiency and neonatal GABA
      potentiation in mice.
AB  - The methylenetetrahydrofolate reductase (Mthfr) gene and/or abnormal homocysteine
      folate metabolism are associated with increased risk for birth defects and
      neuropsychiatric diseases. In addition, disturbances of the GABAergic system in
      the brain as well as Mthfr polymorphism are associated with neurodevelopmental
      disorders such as schizophrenia and autism. In the present study we performed
      behavioral phenotyping of male and female Mthfr mice (wild type and their
      heterozygous littermates). The present study addresses two main questions: (1)
      genetic susceptibility, as examined by effects of Mthfr deficiency on behavior
      (Experiment 1) and (2) possible gene-drug interactions as expressed by behavioral
      phenotyping of Mthfr-deficient mice neonatally exposed to the GABA potentiating
      drug GVG (Experiment 2). Newborn development was slightly influenced by Mthfr
      genotype per se (Experiment 1); however the gene-drug interaction similarly
      affected reflex development in both male and female offspring (Experiment 2).
      Hyperactivity was demonstrated in Mthfr heterozygous male mice (Experiment 1) and
      due to GVG treatment in both Wt and Mthfr+/- male and female mice (Experiment 2).
      The gene-environment interaction did not affect anxiety-related behavior of male
      mice (Experiment 2). In female mice, gene-treatment interactions abolished the
      reduced anxiety observed due to GVG treatment and Mthfr genotype (Experiment 2).
      Finally, recognition memory of adult mice was impaired due to genotype, treatment
      and the gene-treatment combination in a sex-independent manner (Experiment 2).
      Overall, Mthfr deficiency and/or GABA potentiation differentially affect a
      spectrum of behaviors in male and female mice. This study is the first to
      describe behavioral phenotypes due to Mthfr genotype, GVG treatment and the
      interaction between these two factors. The behavioral outcomes suggest that Mthfr
      deficiency modulates the effects of GABA potentiating drugs. These findings
      suggest that future treatment strategies should consider a combination of
      genotyping with drug regimens.

PMID- 20813140
TI  - Microsatellite polymorphism in the sexually transmitted human pathogen
      Trichomonas vaginalis indicates a genetically diverse parasite.
AB  - Given the growing appreciation of serious health sequelae from widespread
      Trichomonas vaginalis infection, new tools are needed to study the parasite's
      genetic diversity. To this end we have identified and characterized a panel of 21
      microsatellites and six single-copy genes from the T. vaginalis genome, using
      seven laboratory strains of diverse origin. We have (1) adapted our
      microsatellite typing method to incorporate affordable fluorescent labeling, (2)
      determined that the microsatellite loci remain stable in parasites continuously
      cultured for up to 17 months, and (3) evaluated microsatellite marker coverage of
      the six chromosomes that comprise the T. vaginalis genome, using fluorescent in
      situ hybridization (FISH). We have used the markers to show that T. vaginalis is
      a genetically diverse parasite in a population of commonly used laboratory
      strains. In addition, we have used phylogenetic methods to infer evolutionary
      relationships from our markers in order to validate their utility in future
      population analyses. Our panel is the first series of robust polymorphic genetic
      markers for T. vaginalis that can be used to classify and monitor lab strains, as
      well as provide a means to measure the genetic diversity and population structure
      of extant and future T. vaginalis isolates.

PMID- 20813142
TI  - Route of administration-dependent anti-inflammatory effect of liposomal
      alendronate.
AB  - Innate immunity and inflammation are of major importance in various pathological
      conditions. Intravenous (IV) and intraperitoneal (IP) liposomal alendronate (LA)
      treatments have been shown to deplete circulating monocytes and peritoneal
      macrophages resulting in the inhibition of restenosis and endometriosis (EM),
      respectively. Nevertheless, the correlation between the extent of circulating
      monocyte depletion and liposome biodistribution is unknown, and the route of
      administration-dependent bioactivity in restenosis and EM has not been
      determined. We found that, LA treatment resulted in a dose-response modified
      biodistribution following both IV and IP administrations. The biodistribution of
      high-dose LA (10mg/kg), but not that of the low-dose (1mg/kg), was similar in
      healthy and diseased animals. It is concluded that LA impedes its own elimination
      from the circulation by depleting circulating monocytes and/or inhibiting their
      endocytic activity, in a dose-dependent manner. Both IV and IP administration of
      LA mediated by the partial and transient depletion of circulating monocytes
      effected inhibition of restenosis. Inhibition of EM was effected only by IP
      administration, which depleted both intraperitoneal and circulating monocytes.
      Thus, EM should be considered as a local inflammatory condition with systemic
      manifestations as opposed to restenosis, a systemic inflammatory disease.

PMID- 20813141
TI  - Identification of inhibitors for putative malaria drug targets among novel
      antimalarial compounds.
AB  - The efficacy of most marketed antimalarial drugs has been compromised by
      evolution of parasite resistance, underscoring an urgent need to find new drugs
      with new mechanisms of action. We have taken a high-throughput approach toward
      identifying novel antimalarial chemical inhibitors of prioritized drug targets
      for Plasmodium falciparum, excluding targets which are inhibited by currently
      used drugs. A screen of commercially available libraries identified 5655 low
      molecular weight compounds that inhibit growth of P. falciparum cultures with
      EC(50) values below 1.25MUM. These compounds were then tested in 384- or 1536
      well biochemical assays for activity against nine Plasmodium enzymes:
      adenylosuccinate synthetase (AdSS), choline kinase (CK), deoxyuridine
      triphosphate nucleotidohydrolase (dUTPase), glutamate dehydrogenase (GDH),
      guanylate kinase (GK), N-myristoyltransferase (NMT), orotidine 5'-monophosphate
      decarboxylase (OMPDC), farnesyl pyrophosphate synthase (FPPS) and S
      adenosylhomocysteine hydrolase (SAHH). These enzymes were selected using
      TDRtargets.org, and are believed to have excellent potential as drug targets
      based on criteria such as their likely essentiality, druggability, and
      amenability to high-throughput biochemical screening. Six of these targets were
      inhibited by one or more of the antimalarial scaffolds and may have potential use
      in drug development, further target validation studies and exploration of P.
      falciparum biochemistry and biology.

PMID- 20813143
TI  - The presence of the peptides apelin, ghrelin and nesfatin-1 in the human breast
      milk, and the lowering of their levels in patients with gestational diabetes
      mellitus.
AB  - Numerous bioactive peptides (such as ghrelins) have been identified in breast
      milk but there is no information concerning apelin and nesfatin-1. Therefore,
      present study was designated to explore whether breast milk contains apelin and
      nesfatin-1, to determine the concentrations and to compare these with serum
      levels. In addition, the concentrations of these peptides were compared in
      patients with gestational diabetes and normal lactating samples. Furthermore,
      this study explored the effectivity of various commercial diagnostic kits for
      determining ghrelin concentrations in breast milk. Ten gestational diabetic
      lactating women (29.1+/-2.2 years old and BMI: 33.2+/-4.8) and 10 control
      lactating women (28.2+/-1.8 years old and BMI: 39.48+/-1.7) were enrolled in the
      study. An ELISA was used to determine concentrations of apelin-36 and -12,
      nesfatin-1, and acylated and desacylated ghrelin in serum, colostrum and mature
      milk. Serum apelin-36 and -12 concentrations were correlated with colostrum and
      mature milk, and the same trends were observed for nesfatin-1. Apelins and
      nesfatin-1 concentrations were higher in mature milk than in colostrum (P<0.05).
      The concentration of apelins, ghrelins and nesfatin-1 in serum and milk in
      gestational diabetic lactating women was lower than in control samples. The
      majority of ghrelin circulating and in milk was the free form (desacylated) in
      both groups of women. This is the first report to describe the presence of
      apelins and nesfatin-1 in breast milk. It is suggested that the source of
      ghrelins, apelins and nesfatin-1 in breast milk is likely to be breast tissue
      (autonomous production). These bioactive peptides found in breast milk could be
      important for growth, energy regulation and maturation of the gastrointestinal
      system in neonates.

PMID- 20813144
TI  - Activation of serotonin 1A receptors in ventrolateral orbital cortex depresses
      persistent nociception: a presynaptic inhibition mechanism.
AB  - The present study examined the effect of serotonin 1A (5-HT(1A)) receptor
      activation in the ventrolateral orbital cortex (VLO) upon formalin-evoked
      flinching behavior and spinal Fos expression, and further determined whether
      activation of 5-HT(1A) receptors affected the spontaneous GABAergic miniature
      inhibitory postsynaptic currents (mIPSCs) in rat VLO slice by pharmacologically
      separated neurons to understand the possible mechanism underlying this effect.
      Microinjection of the 5-HT(1A) receptors agonist 8-OH-DPAT (8-hydro-2-(di-n
      propylamino) tetralin) into the VLO depressed the formalin-evoked nociceptive
      behavior flinching response and the Fos expression in the lumbar spinal cord
      dorsal, which was antagonized by pre-treatment with 5-HT(1A) receptors antagonist
      NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide).
      Furthermore, application of 8-OH-DPAT into VLO slice inhibited GABAergic mIPSC
      frequency in a dose-dependent manner without effects on amplitude of the
      GABAergic mIPSCs, this effect was blocked by NAN-190. These results provide
      evidence for the involvement of 5-HT(1A) receptors in VLO in the modulation of
      persistent inflammatory nociception, and suggest that a presynaptic inhibition of
      the GABA release may contribute to the 5-HT(1A) receptor-mediated descending
      antinociception.

PMID- 20813145
TI  - Aberrant regulation of alternative pre-mRNA splicing in schizophrenia.
AB  - Alternative pre-mRNA splicing plays a key role in the control of gene expression
      in both neurons and glial cells, and failure or dysregulation of these splicing
      events can cause developmental abnormalities and lead to the development of
      pathology. Schizophrenia is a common mental disorder that presents as a complex
      condition. Many factors, of genetic, epigenetic and environmental etiology, such
      as developmental abnormalities in myelination, synapses and neurotransmission,
      have been implicated in this disorder. Intriguingly, aberrant alternative
      splicing of genes related to neurodevelopment and neural function has been
      detected in schizophrenia and related disorders. In this review, we discuss the
      aberrant splicing of specific genes for each candidate cause of schizophrenia.
      Finally, we discuss the only example that has been researched in detail, from the
      cause to clarification of the mechanism, in ongoing studies into the associations
      between brain disorders and abnormal splicing.

PMID- 20813147
TI  - Requirement of both NR3A and NR3B subunits for dominant negative properties on
      Ca2+ mobilization mediated by acquired N-methyl-D-aspartate receptor channels
      into mitochondria.
AB  - Conventional N-methyl-D-aspartate (NMDA) receptor (NMDAR) is a heteromeric
      complex between the essential NR1 subunit and one of NR2A-D subunits toward
      functional channels permeable to Ca(2+) rather than Na(+) ions. Although recent
      studies identified dominant negative NR3A and NR3B subunits, whether these
      subunits inhibit Ca(2+) mobilization through NMDAR channels into mitochondria is
      not clarified so far. In this study, we investigated Ca(2+) influx across
      acquired NMDAR channels composed of different NR subunits artificially expressed
      in HEK293 cells. The addition of NMDA markedly increased intracellular free
      Ca(2+) levels determined by Fluo-3 in cells transfected with either NR2A or NR2B
      subunit together with NR1 subunit. Further addition of dizocilpine completely
      inhibited the increase by NMDA in both types of acquired channels, while the NR2B
      subunit selective antagonist ifenprodil drastically inhibited the increase by
      NMDA in cells expressing NR1/NR2B, but not NR1/NR2A, subunits. Similar
      pharmacological profiles were invariably seen with cell death by NMDA.
      Introduction of both NR3A and NR3B subunits significantly inhibited the increase
      by NMDA in intracellular free Ca(2+) levels in both acquired channels, while
      introduction of either NR3A or NR3B alone was ineffective. Co-expression of both
      NR3A and NR3B subunits was also required for the prevention of increased
      mitochondrial free Ca(2+) levels determined by Rhod-2, as well as decreased
      cellular viability, in cells expressing NR1/NR2A or NR1/NR2B subunits upon
      exposure to NMDA. These results suggest that co-expression of both NR3A and NR3B
      subunits is essential for the dominant negative properties on Ca(2+) mobilization
      through acquired functional NMDAR channels into mitochondria.

PMID- 20813146
TI  - Phenylbutyric acid suppresses protein accumulation-mediated ER stress in
      retrovirus-infected astrocytes and delays onset of paralysis in infected mice.
AB  - Many neurodegenerative diseases are associated with accumulation of misfolded
      proteins in cells of the central nervous system (CNS). We have previously
      reported that accumulation of the precursor envelope protein gPr80(env) of ts1, a
      mutant of Moloney murine leukemia virus (MoMuLV), in the endoplasmic reticulum
      (ER) of infected astrocytes, results in ER stress, oxidative stress and cell
      death, subsequently leading to ts1-mediated neurodegeneration in infected mice.
      In the present study, we assessed whether treatments that reduce the accumulation
      of gPr80(env) in the ER of ts1-infected astrocytes provided a protective effect
      against ER stress and cell death. We show that treatment with phenylbutyric acid
      (PBA) can prevent the unfolded protein response (UPR), ER stress and cell death
      in cultured ts1-infected astrocytes. The protective effect of PBA is associated
      with its ability to reduce gPr80(env) accumulation and to increase the expression
      of proteins involved in protein folding in the ER, such as protein disulfide
      isomerase (PDI) and ERp44, rather than by decrease mRNA levels of gPr80(env) or
      alter the proteasomal degradation process for gPr80(env). In infected mice
      treated with PBA we also noted a reduction in the severity of the neuropathology
      in brainstem tissues and a delayed onset of paralysis. These results show that
      PBA is a potentially effective drug for the treatment of neurodegeneration caused
      by protein accumulation in cells of the CNS.

PMID- 20813148
TI  - In vitro findings of alterations in intracellular calcium homeostasis in
      schizophrenia.
AB  - The pathogenesis of schizophrenia involves several complex cellular mechanisms
      and is not well understood. Recent research has demonstrated an association
      between primary disturbances characteristic of the disease, including altered
      dopaminergic and glutamatergic neurotransmission, and impairments in neuronal
      calcium (Ca(2+)) homeostasis and signaling. Emerging Ca(2+) hypothesis links and
      unifies various cellular processes involved in the pathogenesis of schizophrenia
      and suggests a central role of dysregulation of Ca(2+) homeostasis in the
      etiology of the disease. This review explores the in vitro data on Ca(2+)
      homeostasis and signaling in schizophrenia. Major limitation in this research is
      the lack of schizophrenia markers and validated disease models. As indicated in
      this review, one way to overcome these limitations may be analyses of Ca(2+)
      signalosomes in peripheral cells from schizophrenia patients. Validation of
      animal models of schizophrenia may permit the application of advanced Ca(2+)
      imaging techniques in living animals.

PMID- 20813149
TI  - Bacillus species enhance growth parameters of chickpea (Cicer arietinum L.) in
      chromium stressed soils.
AB  - Pollution of the agricultural land by the toxic chromium is a global threat that
      has accelerated dramatically since the beginning of industrial revolution. Toxic
      chromium affects both the microbial diversity as well as reduces the growth of
      the plants. Understanding the effect of the chromium reducing and plant growth
      promoting rhizobacteria on chickpea crop will be useful. Chromium reducing and
      plant growth promoting Bacillus species PSB10 significantly improved growth,
      nodulation, chlorophyll, leghaemoglobin, seed yield and grain protein of chickpea
      crop grown in the presence of different concentrations of chromium compared to
      the plants grown in the absence of bio-inoculant. The strain also reduced the
      uptake of chromium in roots, shoots and grains of chickpea crop compared to
      plants grown in the absence of bio-inoculant. This study thus suggested that the
      Bacillus species PSB10 due to its intrinsic abilities of growth promotion and
      attenuation of the toxic effects of chromium could be exploited for remediation
      of chromium from chromium contaminated sites.

PMID- 20813150
TI  - Reproductive toxicity of methomyl insecticide in male rats and protective effect
      of folic acid.
AB  - The acute toxicity (LD(50)) of insecticide methomyl and its effects on male
      reproduction in rats were carried out. Methomyl was given orally to male rats
      daily for 65 successive days at two doses (0.5 and 1.0 mg kg(-1) b.wt.,
      corresponding to 1/40 and 1/20 LD(50)) alone and in combination with folic acid
      (1.1 mg kg(-1) b.wt., corresponding to acceptable daily intake, ADI). Fertility
      index, weight of sexual organs, semen picture, serum testosterone level and
      histopathology of testes were the parameters used to evaluate the reproductive
      efficiency of treated rats. The reversibility of methomyl effects was also
      studied after 65 days post-administration. The oral LD(50) of methomyl was 20.0
      mg kg(-1) b.wt. in male rats. Methomyl significantly decreased the fertility
      index, weight of testes and accessory male sexual glands, serum testosterone
      level and sperm motility and count, but increased sperm cell abnormality. It
      induced testicular lesions characterized by moderate to severe degenerative
      changes of seminiferous tubules and incomplete arrest of spermatogenesis. These
      toxic effects were not persistent (reversible). Coadministration of folic acid
      with methomyl decreased its reproductive toxicity. A great attention should be
      taken during field application of methomyl to avoid its deleterious effects in
      farm animals and occupationally exposed humans.

PMID- 20813151
TI  - The influence of opaque application methods on the bond strength and final shade
      of PFM restorations.
AB  - OBJECTIVES: The aim of this study is to compare the influence of the opaque
      application method on the adhesion and final shade of porcelain-fused-to-metal
      restorations. METHODS: Four samples (n=12) were cast in a NiCrMo alloy and
      opaqued using three application methods: aerosol-spray (one application), aerosol
      spray (two applications), paste and powder-liquid prior to veneering with dentine
      porcelain to a thickness of 1.0mm to mimic the clinical thickness of porcelain
      fused-to-metal crowns. The porcelain to metal adhesion was determined by
      measuring the interfacial fracture toughness or strain energy release rate with a
      four-point bending configuration developed by Charalambides et al.,(13) at a
      loading rate of 0.05mm min(-1) in kerosene. The resultant porcelain shade was
      measured with a spectrophotometer under daylight. Values of L*, a* and b* were
      used to calculate the total color difference DeltaE with different equations
      CIELAB, CMC(1:1), CIE94, and CIEDE2000. The resulting values were also compared
      with a reference unbonded sample made from the same dentine porcelain used to
      veneer the porcelain-fused-to-metal specimens. RESULTS: The application technique
      of the opaque did not influence the adhesion between the porcelain and metal. All
      the application methods demonstrated brittle cracking behaviour through the
      opaque layer. No visible color differences were found between the applications
      methods in the final shade of the porcelain. SIGNIFICANCE: The application method
      in terms of bond strength and final porcelain shade is not a factor in choosing
      which method to use in the dental laboratory.

PMID- 20813152
TI  - Implicit memory for emotional words is modulated by cardiac perception.
AB  - In the present study we investigated the impact of viscero-sensory feedback on
      memory performance. Participants with good and poor perception of their heart
      activity were presented with positive, negative and neutral words while heart
      rate and skin conductance were measured. After a distractor task, participants
      were asked to complete primed and unprimed wordstems. Implicit memory performance
      was assessed in terms of accuracy of completion. In our study, participants with
      good cardiac perception completed significantly more wordstems of previously
      presented positive and negative words, whereas no group differences were found
      for wordstems of neutral words and physiological measures during encoding. Our
      findings document a substantial role of visceral feedback in implicit memory
      processes. They are in line with Damasio's somatic marker hypothesis stating that
      access to information about somatic processes facilitates cognitive processing.

PMID- 20813153
TI  - Intrinsic and extrinsic effects of mafG deficiency on hematopoietic recovery
      following bone marrow transplant.
AB  - OBJECTIVE: MafG is the small subunit of the transcription factor NF-E2 that
      controls terminal megakaryocyte maturation and platelet release. Studies were
      conducted to evaluate the intrinsic and extrinsic effects of mafG deficiency on
      bone marrow engraftment kinetics. MATERIALS AND METHODS: We used mafG knockout
      mice either as donors or recipients in bone marrow transplantations with wild
      type mice and compared the engraftment kinetics to transplantations using wild
      type donors and recipients. We measured peripheral cell counts, the presence of
      circulating donor-derived cells by flow cytometry, changes in the cellularity of
      the bone marrow and splenic weight on day 5, 7, 14, and 1 month post
      transplantation. RESULTS: Compared to wild-type recipients, mafG recipients had
      delayed platelet and leukocyte recovery and lower spleen weight at early time
      points after transplantation. Intrinsic effects: When mafG-deficient bone marrow
      served as donor source, we observed more rapid recovery of bone marrow
      cellularity and increased splenic hematopoiesis. The finding of increased short
      term hematopoietic stem cells and progenitors in the mafG-deficient bone marrow
      could explain the accelerated hematopoietic recovery after transplantation.
      Furthermore, the expression of Bach 2, which can form a heterodimer with mafG
      protein, was found to be greatly reduced, while Notch 1 expression was increased
      in mafG-deficient mice. Extrinsic effects: When mafG-deficient mice were
      transplant recipients, there were delays in recovery of normal levels of marrow
      and splenic hematopoiesis as well as circulating leukocytes and platelets.
      CONCLUSIONS: Our study demonstrates that mafG expression has intrinsic and
      extrinsic effects on hematopoietic engraftment following bone marrow
      transplantation.

PMID- 20813154
TI  - NF-kappaB mediates aberrant activation of HIF-1 in malignant lymphoma.
AB  - OBJECTIVE: The goal of this study was to explore the molecular mechanisms of
      aberrant hypoxia inducible factor-1 (HIF-1) activation in lymphoma cells.
      MATERIALS AND METHODS: We analyzed the expression of the alpha subunit of HIF-1
      in three lymphoma cell lines and in normal CD19-positive B cells by Western
      blotting. To investigate the role of nuclear factor (NF)-kappaB in abnormal HIF
      1alpha expression in lymphoma cells, we performed a reporter assay using HIF
      1alpha promoter constructs that contained or lacked an NF-kappaB binding site. We
      also used a chromatin immunoprecipitation assay to assess whether NF-kappaB binds
      the HIF-1alpha promoter. In addition, we took advantage of NF-kappaB inhibitors.
      To analyze the function of HIF-1 in lymphoma cells, we established stable HIF
      1alpha knockdown cells using short-hairpin RNA. RESULTS: Malignant lymphoma
      cells, but not normal B cells, demonstrated constitutive expression of HIF
      1alpha. Inhibitors of NF-kappaB, however, drastically suppressed this HIF-1alpha
      expression at both the messenger RNA and protein levels. Furthermore, we found
      that exposure of lymphoma cells to ionizing radiation clearly induced NF-kappaB
      activation and increased HIF-1alpha expression. Suppressing HIF-1alpha expression
      by short-hairpin RNA increased the sensitivity of lymphoma cells to ionizing
      radiation-induced cell death. In searching for downstream targets of the NF
      kappaB/HIF-1 axis, we identified survivin, a member of the IAP family of anti
      apoptotic proteins. CONCLUSIONS: We found that aberrant activation of HIF-1 in
      malignant lymphoma cells was mediated, at least in part, by NF-kappaB activity.
      Our observations suggest that HIF-1 inhibition may be an effective strategy to
      improve the outcomes of lymphoma patients treated with radiation.

PMID- 20813155
TI  - P wave dispersion in patients with hypochondriasis.
AB  - P wave dispersion (Pd), defined as the difference between the maximum and the
      minimum P wave duration, has been associated with anxiety. Thus, we wondered
      whether Pd in hypochondriasis which is associated with anxiety differed from that
      in healthy controls. Pd was measured in 30 hypochondriac patients and same number
      of physically and mentally healthy age- and gender-matched controls. Hamilton
      Depression Rating (HDRS) and Hamilton Anxiety Rating Scales (HARS) were scored.
      The heart rate and left atrium (LA) sizes were not significantly different
      between groups. However, both Pmax and Pmin values of the patients were
      significantly higher than those of healthy controls. As for the main variable
      investigated in the present study, the corrected Pd was significantly longer in
      the patient group compared to control group. On the basis of this study, we can
      conclude that Pd may be related to hypochondriasis though our sample is too small
      to allow us to obtain a clear conclusion. Future studies with larger sample
      evaluating the effects of treatment are required.

PMID- 20813156
TI  - Electro-acupuncture protects against hypoxic-ischemic brain-damaged immature rat
      via hydrogen sulfide as a possible mediator.
AB  - We investigated whether hydrogen sulfide (H(2)S) may be a mediator of electro
      acupuncture (EA) stimulation treatment for hypoxic-ischemic brain-damage (HIBD).
      We studied a HIBD 7-day-old rat model with 4 types of treatments: (1) 14 sessions
      of EA; (2) hydroxylamine (HA), an inhibitor of cystathionine-beta-synthase (CBS),
      the key enzyme of H(2)S generation; (3) both EA and HA; or (4) no treatment. Sham
      treated rats with or without EA were also studied. Regional cerebral blood flow
      (rCBF) was monitored before, during and after EA at different periods of
      treatment (d1, 7 and 14 sessions). We evaluated motor function, H(2)S levels and
      CBS expression in the cerebral cortex and prepared cerebral pathomorphological
      images after 14 sessions of treatment. EA stimulation could increase local blood
      circulation and improve motor function in HIBD rats. HIBD significantly increased
      H(2)S levels of brain tissue as compared with sham treatment, and EA treatment
      could decrease the H(2)S generation. Rats with HIBD receiving both EA and HA
      therapy showed greatly recovered motor function and brain morphology. H(2)S might
      be a mediator of EA treatment of HIBD in rats.

PMID- 20813157
TI  - Modulation of potassium channels via the alpha1B-adrenergic receptor in human
      osteoblasts.
AB  - Recent studies have demonstrated the involvement of the sympathetic nerve system
      in bone metabolism. We have previously demonstrated the expression of adrenergic
      receptors in the human osteoblast SaM-1 cell line. The aim of this study was to
      reveal the function of these receptors in osteoblasts using electrophysiological
      methods. During whole-cell patch clamp recording, the application of
      noradrenaline reduced the currents induced by a voltage ramp, and the effect was
      larger in the positive potential range. Pretreatment with the selective alpha(1B)
      adrenergic receptor antagonist chloroethylclonidine eliminated the inhibitory
      effect of noradrenaline. Using Cs-based pipette solution to block potassium
      channels, the inhibitory effect of noradrenaline disappeared. In contrast, the
      effect was unaffected in the presence of tetraethylammonium (TEA), a potassium
      channel blocker. These results suggest that noradrenaline suppresses Cs-sensitive
      and TEA-insensitive potassium channels via the alpha(1B)-adrenergic receptor in
      human osteoblasts.

PMID- 20813158
TI  - Efferent-induced change in human cochlear compression and its influence on
      masking of tones.
AB  - Several lines of evidence suggest that medial olivocochlear (MOC) efferent
      neurons modify cochlear output to improve signal detection in noise. In animal
      models, stimulation of MOC efferents reduces the amount of compression in basilar
      membrane (BM) growth functions. Linearization of BM growth functions may assist
      in extending the neural response to the signal above that of noise, leading to a
      decrease in masking. In order to test this hypothesis, effects of MOC efferent
      neurons on BM compression were studied indirectly in humans by examining the
      effects of contralateral noise on distortion-product otoacoustic emission (DPOAE)
      input-output functions at 1.0 and 2.0kHz. Compression threshold estimates from a
      three-segment linear regression model applied to the DPOAE functions were derived
      in order to determine correlations with psychophysical measurements of masking of
      tones at 1.0 and 2.0kHz. Contralateral noise shifted the DPOAE compression
      threshold to a significantly higher level at 1.0kHz, but not at 2.0kHz. A
      significant negative correlation between the change in DPOAE compression
      threshold and the amount of masking at 1.0kHz was observed, but no correlation
      between these variables was detected at 2.0kHz. The results of this experiment at
      the lower test frequency indicated that contralateral noise linearized DPOAE
      input-output functions, and individuals with larger DPOAE compression threshold
      shifts tended to exhibit less masking. Under certain conditions, decreases in
      cochlear compression induced by MOC efferent neurons may lead to unmasking of
      tones presented in noise.

PMID- 20813159
TI  - Borderline intellectual functioning and sleep: the role of cyclic alternating
      pattern.
AB  - In the clinical literature there are few specific studies about the relationship
      between cognition processes and sleep during childhood. In addition, milder
      deficits in general intellectual capacity have received less attention relative
      to major cognitive dysfunctions (such as the genetic or environmental basis of
      mental retardation), especially concerning the low normal and borderline status.
      Sleep could play a key role in multiple intellectual abilities such as memory,
      executive functions, and school performances. Aim of our study is to assess the
      sleep macrostructure and NREM instability (cyclic alternating pattern) and their
      relationship with IQ in a sample of subjects with borderline intellectual
      functioning (BIF). The DSM-IV defines BIF as a total intelligence quotient (TIQ)
      ranging between 71 and 84. Intellective functioning was assessed using the
      Italian version of Wechsler Intelligence Scale for Children-Revised (WISC-R), a
      well validated test for the developmental age between 6 and 16. For this study,
      12 BIF and 17 healthy children, matched for sex and age, underwent an overnight
      PSG recording. Macrostructural sleep and CAP analysis were also performed. To our
      knowledge, this study represents the first attempt to evaluate sleep architecture
      and NREM instability organization in children with BIF. Findings from this
      investigation evidence that BIF presents alterations in both macro- and
      microstructural sleep architecture, with an interesting statistical significant
      correlation with IQ.

PMID- 20813160
TI  - Nicotine activation of neuronal nitric oxide synthase and guanylyl cyclase in the
      medulla increases blood flow of the common carotid artery in cats.
AB  - Individual activation of nicotinic acetylcholine receptor (nAChR) or nitric oxide
      (NO) synthase in the dorsal facial area (DFA) increases blood flow of common
      carotid artery (CCA) supplying intra- and extra-cranial tissues. We investigated
      whether the activation of nAChR initiated the activation of NO synthase and
      guanylyl cyclase to increase CCA blood flow in anesthetized cats. Microinjections
      of nicotine (a non-selective nAChR agonist), or choline (a selective alpha7-nAChR
      agonist) in the DFA produced increases in CCA blood flow ipsilaterally. These
      increases were significantly reduced by pretreatment with NG-nitro-arginine
      methyl ester (l-NAME, a non-specific NO synthase inhibitor), 7-nitroindazole (7
      NI, a relatively selective neuronal NO synthase inhibitor) or methylene blue (MB,
      a guanylyl cyclase inhibitor) but not by that with N5-(1-iminoethyl)-l-ornithine
      (l-NIO, a potent endothelial NO synthase inhibitor). Control microinjection with
      d-NAME (an isomer of l-NAME), artificial cerebrospinal fluid or DMSO (a solvent
      for 7-NI) did not affect resting CCA blood flow, nor did they affect nicotine- or
      choline-induced response. In conclusion, activation of nAChR, at least alpha7
      nAChR, led to the activation of neuronal NO synthase and guanylyl cyclase in the
      DFA, which induced an increase in CCA blood flow.

PMID- 20813161
TI  - Chrysin suppresses LPS-stimulated proinflammatory responses by blocking NF-kappaB
      and JNK activations in microglia cells.
AB  - Neuroinflammation mediated by microglia has been implicated in neurodegenerative
      diseases. Suppression of microglial activation may therefore contribute to
      neuronal cell survival. Chrysin is present in honey and propolis and in low
      concentrations in fruits, vegetables, and certain beverages. It has been reported
      that chrysin has potent anti-inflammation, anti-cancer, and anti-oxidation
      properties. In the present study, we investigated the effects of chrysin on the
      production of proinflammatory mediators in lipopolysaccharide (LPS)-stimulated
      microglia. Chrysin significantly inhibited the release of nitric oxide (NO) and
      proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1beta (IL-1beta). The expressions of inducible NO synthase (iNOS) and
      cyclooxygenase-2 (COX-2) were also significantly inhibited by chrysin.
      Furthermore, chrysin inhibited the activations of c-Jun N-terminal kinase (JNK)
      and nuclear factor-kappaB (NF-kappaB), which are signaling molecules involved in
      neuroinflammation. These results suggest that chrysin may act as a potential
      therapeutic agent for various neurodegenerative diseases involving
      neuroinflammation.

PMID- 20813162
TI  - Hydrogen peroxide induces apoptosis through the mitochondrial pathway in rat
      Schwann cells.
AB  - Oxidative stress is one of the several mechanisms that induces apoptosis in
      cells. It has been shown that hydrogen peroxide (H(2)O(2)) induces apoptosis in
      several kinds of cells; however, the role of H(2)O(2) in the apoptosis of Schwann
      cells (SCs) is currently unclear. The objective of this study was to determine
      whether H(2)O(2) is capable of inducing apoptosis in SCs and whether or not such
      an effect is associated with the activation of mitochondrial pathway. We
      demonstrated that H(2)O(2) induces apoptosis in SCs, and is associated with
      increased release of cytochrome c from mitochondria and the activation of caspase
      3 and -9 by up-regulation of Bax and down-regulation of Bcl-2. These results
      suggest a potential role for H(2)O(2) in SC injury by triggering apoptosis via
      the mitochondrial pathway under oxidative stress.

PMID- 20813163
TI  - Neuronal voltage-gated K+ (Kv) channels function in macromolecular complexes.
AB  - Considerable evidence indicates that native neuronal voltage-gated K+ (Kv)
      currents reflect the functioning of macromolecular Kv channel complexes, composed
      of pore-forming (alpha)-subunits, cytosolic and transmembrane accessory subunits,
      together with regulatory and scaffolding proteins. The individual components of
      these macromolecular complexes appear to influence the stability, the
      trafficking, the localization and/or the biophysical properties of the channels.
      Recent studies suggest that Kv channel accessory subunits subserve multiple roles
      in the generation of native neuronal Kv channels. Additional recent findings
      suggest that Kv channel accessory subunits can respond to changes in
      intracellular Ca(2+) or metabolism and thereby integrate signaling pathways to
      regulate Kv channel expression and properties. Although studies in heterologous
      cells have provided important insights into the effects of accessory subunits on
      Kv channel expression/properties, it has become increasingly clear that
      experiments in neurons are required to define the physiological roles of Kv
      channel accessory and associated proteins. A number of technological and
      experimental hurdles remain that must be overcome in the design, execution and
      interpretation of experiments aimed at detailing the functional roles of
      accessory subunits and associated proteins in the generation of native neuronal
      Kv channels. With the increasing association of altered Kv channel functioning
      with neurological disorders, the potential impact of these efforts is clear.

PMID- 20813164
TI  - Observer-independent characterization of sulcal landmarks and depth asymmetry in
      the central sulcus of the chimpanzee brain.
AB  - The central sulcus (CS) divides primary motor and sensory cortex in many
      mammalian brains. Recent studies have shown that experiential factors can
      influence the volume and lateralization of the CS in both human and nonhuman
      primates. In this study, we sought to define specific landmarks and the depth of
      the CS region corresponding to the motor-hand area of chimpanzees for comparison
      with humans using a novel, observer independent method applied to sample of 32
      magnetic resonance images (MRI) scans. Our results showed that the dorsal-ventral
      location of the motor-hand region is comparable between humans and chimpanzees,
      though the depth of the CS was significantly greater in humans compared to
      chimpanzees. We further found that CS area corresponding to the motor-hand area
      was significantly larger in the hemisphere contralateral to the chimpanzees
      preferred hand. The methods employed here offer some potential advantages over
      traditional region-of-interest in the comparative study of cortical organization
      and gyrification in primates and are discussed.

PMID- 20813165
TI  - Astroglial connexin immunoreactivity is specifically altered at beta-amyloid
      plaques in beta-amyloid precursor protein/presenilin1 mice.
AB  - Activation of astrocytes surrounding amyloid plaques is a hallmark of Alzheimer
      disease (AD) with consequences yet poorly understood. Astrocytes are
      characterized by a high level of intercellular communication mediated by two gap
      junction forming proteins, connexin-43 and connexin-30. As astroglial connexins
      (Cxs) are involved in neuronal dysfunctions and death, we have analyzed their
      expression pattern in two murine models of AD, that is two different beta-amyloid
      precursor protein (APP)/presenilin1(PS1) mice, using western blot and
      immunohistochemistry analyzed in confocal microscopy. In young mice at 2 months,
      before the emergence of beta-amyloid (Abeta) deposits, the distribution of both
      Cxs was similar to that of control mice. In older animals>=4 months, local
      modifications in connexin immunostaining pattern were observed in the
      microenvironment of dense core Abeta plaques. In a majority of plaques, an
      elevated immunoreactivity was detected for both Cxs contributing to the overall
      increase in connexin expression detected in 18 month old APP/PS1 mice. Activated
      microglial cells did not contribute to the elevated connexin immunoreactivity
      that was concentrated in astroglial processes infiltrating the plaques. In a
      small proportion of plaques (<=15%) a depletion of immunoreactive connexin puncta
      was also found. As astroglial Cxs participate in neuroglial interactions, their
      remodeling may contribute to neuronal alterations observed at the periplaque
      area.

PMID- 20813166
TI  - Protective effect of montelukast against quinolinic acid/malonic acid induced
      neurotoxicity: possible behavioral, biochemical, mitochondrial and tumor necrosis
      factor-alpha level alterations in rats.
AB  - The present study has been designed to explore the protective effect of
      montelukast (leukotriene receptor antagonist) against intrastriatal quinolinic
      acid (QA; 300 nmol) and malonic acid (MA; 6 MUmol) induced Huntington's like
      symptoms in rats. Quinolinic acid has been reported to induce excitotoxicity by
      stimulating the N-methyl-D-aspartate receptor, causing calcium overload which in
      turn leads to the neurodegeneration. On the other hand, MA, being a reversible
      inhibitor of mitochondrial enzyme complex-II, leads to energy crisis and free
      radical generation. Recent studies have reported the therapeutic potential of
      leukotriene receptor antagonists in different neurodegenerative disorders.
      However, their exact role is yet to be established. The present study
      accordingly, is an attempt to investigate the effect of montelukast against QA
      and MA induced behavioral, biochemical and molecular alterations in rat striatum.
      Oxidative stress, mitochondrial enzyme complex and tumor necrosis factor-alpha
      (TNF-alpha) were evaluated on day 21st and 14th post intrastriatal QA and MA
      treatment, respectively. Findings of the present study demonstrate significant
      alteration in the locomotor activity and motor coordination as well as oxidative
      burden (increased lipid peroxidation, nitrite concentration and decreased
      endogenous antioxidants), mitochondrial enzyme complex (I, II and IV) activities
      and TNF-alpha level, in both intrastriatal QA and MA treated animals. Further,
      montelukast (0.4, 0.8 mg/kg p.o.) treatment for 21 and 14 days respectively,
      attenuated the behavioral alterations, oxidative stress, mitochondrial
      dysfunction and TNF-alpha level in these models of Huntington's disease in a
      significant manner. In conclusion, the present study emphasizes the
      neuroprotective potential of montelukast in the therapeutic management of
      Huntington like symptoms.

PMID- 20813168
TI  - Ameliorative effect of Yokukansan on social isolation-induced aggressive behavior
      of zinc-deficient young mice.
AB  - Yokukansan, a traditional Japanese medicine has been used to cure
      neuropsychological disorders. In the present study, the effect of Yokukansan on
      social isolation-induced aggressive behavior was examined in zinc-deficient mice,
      which were fed a zinc-deficient diet and a drinking water containing Yokukansan
      for 2 weeks. In the resident-intruder test, the rate of mice that exhibited
      aggressive behavior in zinc-deficient mice, which was significantly higher than
      that in the control mice, was significantly decreased by administration of
      Yokukansan. The basal level of serum glucocorticoid, which was significantly
      higher in zinc-deficient mice, was lowered by administration of Yokukansan. On
      the other hand, serum glucocorticoid levels after the resident-intruder test were
      almost the same between the control and zinc-deficient mice. However,
      administration of Yokukansan to zinc-deficient mice significantly increased serum
      glucocorticoid level after the resident-intruder test and the significant
      difference in the rate of serum corticosterone level after the test to the basal
      level between the control and zinc-deficient mice was abolished. Dietary zinc
      deficiency increases the basal levels of serum glucocorticoid, while may
      insufficiently increase serum glucocorticoid levels in the resident-intruder
      test. The concentrations of glutamate and GABA (gamma-aminobutyric acid) in the
      brain were significantly higher in zinc-deficient mice, while Yokukansan
      ameliorated the significant increases. These results indicate that Yokukansan
      ameliorates social isolation-induced aggressive behavior of zinc-deficient mice,
      probably via amelioration of abnormal glucocorticoid secretion. The ameliorative
      effect seems to be linked to the modification of glutamatergic neuron activity
      after administration of Yokukansan.

PMID- 20813167
TI  - Derangements of post-ischemic cerebral blood flow by protein kinase C delta.
AB  - Cerebral ischemia causes blood flow derangements characterized by hyperemia
      (increased cerebral blood flow, CBF) and subsequent hypoperfusion (decreased
      CBF). We previously demonstrated that protein kinase C delta (deltaPKC) plays an
      important role in hippocampal neuronal death after ischemia. However, whether
      part of this protection is due to the role of deltaPKC on CBF following cerebral
      ischemia remains poorly understood. We hypothesized that deltaPKC exacerbates
      hyperemia and subsequent hypoperfusion resulting in CBF derangements following
      ischemia. Sprague-Dawley (SD) rats pretreated with a deltaPKC specific inhibitor
      (deltaV1-1, 0.5 mg/kg) exhibited attenuation of hyperemia and latent
      hypoperfusion characterized by vasoconstriction followed by vasodilation of
      microvessels after 2-vessel occlusion plus hypotension measured by 2-photon
      microscopy. In an asphyxial cardiac arrest model (ACA), SD rats treated with
      deltaV1-1 (pre- and post-ischemia) exhibited improved perfusion after 24 h and
      less hippocampal CA1 neuronal death 7 days after ACA. These results suggest
      possible therapeutic potential of deltaPKC in modulating CBF and neuronal damage
      after cerebral ischemia.

PMID- 20813169
TI  - MK-801, a noncompetitive NMDA receptor antagonist, elicits circling behavior in
      the genetically inbred Balb/c mouse strain.
AB  - The Balb/c mouse is behaviorally hypersensitive to effects of MK-801
      (dizocilpine), a noncompetitive NMDA receptor antagonist, and displays impaired
      sociability. In the current investigation, MK-801-elicited circling behavior in
      the genetically inbred Balb/c mouse strain that was either not or only minimally
      observed in similarly treated outbred Swiss-Webster mice. The ability of
      compounds to attenuate the intensity of MK-801-elicited circling behavior in the
      Balb/c mouse strain may serve as a preclinical screening paradigm for identifying
      effective NMDA receptor agonist interventions in the intact animal; ideally,
      these compounds would have therapeutic value in neuropsychiatric disorders
      associated with impaired sociability, such as schizophrenia and autism spectrum
      disorders (ASD).

PMID- 20813170
TI  - Expression of PLA2G6 in human fetal development: Implications for infantile
      neuroaxonal dystrophy.
AB  - Mutations in PLA2G6, which encodes calcium-independent phospholipase A(2) group
      VIA (iPLA2-VIA), underlie the autosomal recessive disorder infantile neuroaxonal
      dystrophy (INAD). INAD typically presents in the first year of life, and leads to
      optic atrophy and psychomotor regression. We have examined PLA2G6 expression in
      early human embryonic development by in situ hybridization. At Carnegie Stage
      (CS) 19 (approximately 7 post-conception weeks [PCW]), strong expression is
      evident in the ventricular zone (VZ) of midbrain and forebrain suggestive of
      expression in neural stem and progenitor cells. At CS23 (8PCW) expression is also
      detectable in the VZ of the hindbrain and the subventricular zone (SVZ) of the
      developing neocortex, ganglionic eminences and diencephalon. By 9PCW strong
      expression in the post-mitotic cells of the cortical plate can be seen in the
      developing neocortex. In the eye, expression is seen in the lens and retina at
      all stages examined. PLA2G6 expression is also evident in the alar plate of the
      spinal cord, dorsal root ganglia, the retina and lens in the eye and several non
      neuronal tissues, including developing bones, lung, kidney and gut. These
      findings suggest a role for PLA2G6 in neuronal proliferation throughout the
      developing brain and in maturing neurons in the cortical plate and hindbrain.
      Although widespread PLA2G6 expression is detected in neuronal tissues, the
      pattern shows dynamic changes with time and indicates that INAD pathogenesis may
      begin prior to birth.

PMID- 20813171
TI  - Levodopa analgesia in experimental neuropathic pain.
AB  - Levodopa has been shown to produce analgesia in various clinical and experimental
      settings, but its use for chronic pain treatment has not been established. We
      have undertaken a study of the antiallodynic actions of levodopa in a rat model
      of painful mononeuropathy. When administered systemically, levodopa produced a
      decrease in tactile and cold allodynia lasting at least 3h. Direct intrathecal
      (i.t.) levodopa injection at lumbar levels produced a similar, though shorter,
      antiallodynic effect. This effect was blocked by the D2-type receptor antagonist
      sulpiride, which supports the involvement of the spinal dopaminergic system in
      the analgesic action of levodopa on neuropathic pain. These results provide
      experimental support on the antiallodynic effect of levodopa in neuropathic pain
      and suggest that at least part of the analgesic action takes place in the spinal
      cord and involves dopaminergic D2-type receptors.

PMID- 20813173
TI  - Mitochondrial signaling pathway is also involved in bisphenol A induced germ cell
      apoptosis in testes.
AB  - Bisphenol A (BPA) is a potential endocrine disruptor and testicular toxicant. An
      earlier study showed that BPA-induced germ cell apoptosis through the Fas/FasL
      apoptotic pathway. In the present study, we aimed to investigate whether the
      mitochondrial pathway is also involved in the process of BPA-mediated germ cell
      apoptosis in testes. Male mice were administered with BPA (160 or 480 mg/kg) by
      gavage daily from postnatal day 35 (PND35) to PND49. Germ cell apoptosis in
      testes was determined by terminal deoxynucleotidyl transferase (TdT)-mediated
      dUTP nick-end labeling (TUNEL). As expected, the number of TUNEL+ germ cells per
      tubule and the percentage of tubules with TUNEL+ germ cells were significantly
      increased in testes of mice treated with BPA during puberty. TUNEL+ germ cells
      were observed mainly in stages VII-VIII seminiferous tubules in testes. An
      increase in the level of Fas and FasL was observed in testes of mice exposed to
      BPA during puberty. In addition, pubertal BPA exposure evoked the activation of
      caspase-8 and caspase-3 in testes. Interestingly, pubertal BPA exposure also
      caused the translocation of cytochrome c from mitochondria into cytosol. In
      addition, pubertal BPA exposure upregulated the level of Bax and active caspase-9
      in testes. Taken together, these results suggest that pubertal BPA exposure
      induces germ cell apoptosis in testes through not only the Fas/FasL signaling
      pathway but also the mitochondrial apoptotic pathway.

PMID- 20813172
TI  - Perinatal exposure to polychlorinated biphenyls alters social behaviors in rats.
AB  - Perinatal exposure to polychlorinated biphenyls (PCBs) leads to significant
      alterations of neural and hormonal systems. These alterations have been shown to
      impair motor and sensory development. Less is known about the influence of PCB
      exposure on developing emotional and motivational systems involved in social
      interactions and social learning. The present study examined the impact of
      perinatal PCB exposure (mixture of congeners 47 and 77) on social recognition in
      juvenile animals, conspecific-directed investigation in adults and on neural and
      hormonal systems involved in social functions. We used a standard habituation
      dishabituation paradigm to evaluate juvenile recognition and a social port
      paradigm to monitor adult social investigation. Areal measures of the
      periventricular nucleus (PVN) of the hypothalamus were obtained to provide
      correlations with related hormone and brain systems. PCB exposed rats were
      significantly impaired in social recognition as indicated by persistent
      conspecific-directed exploration by juvenile animals regardless of social
      experience. As adults, PCB exposure led to a dampening of the isolation-induced
      enhancement of social investigation. There was not a concomitant alteration of
      social investigation in pair-housed PCB exposed animals at this stage of
      development. Interestingly, PVN area was significantly decreased in juvenile
      animals exposed to PCB during the perinatal period. Shifts in hypothalamic
      regulation of hormones involved in social behavior and stress could be involved
      in the behavioral changes observed. Overall, the results suggest that PCB
      exposure impairs context or experience-dependent modulation of social approach
      and investigation. These types of social-context deficits are similar to
      behavioral deficits observed in social disorders such as autism and other
      pervasive developmental disorders.

PMID- 20813174
TI  - Ionic liquid-in-oil microemulsion as a potential carrier of sparingly soluble
      drug: characterization and cytotoxicity evaluation.
AB  - Pharmaceutical industries have posed challenges in the topical and transdermal
      administration of drugs which are poorly soluble or insoluble in water and most
      of organic solvents. In an approach to overcome this limitation, ionic liquid-in
      oil (IL/o) microemulsions (MEs) were employed to increase the solubility of a
      sparingly soluble drug to enhance its topical and transdermal delivery. The
      formulation of MEs was composed of a blend of nonionic surfactants,
      polyoxyethylene sorbitan monooleate (Tween-80) and sorbitan laurate (Span-20),
      isopropyl myristate (IPM) as an oil phase, and IL [C(1)mim] [(CH(3)O)(2)PO(2)]
      (dimethylimidazolium dimethylphosphate) as a pseudophase. Among various weight
      ratios of Tween-80 to Span-20 investigated in the ME systems, the ratio 3:2
      showed excellent solubility and skin permeation enhancing effect for acyclovir
      (ACV) used as a model sparingly soluble drug. The size and size distribution of
      the ME droplets with and without drug were determined by dynamic light
      scattering. The permeability study of ACV incorporated in IL droplets as well as
      other formulations was performed into and across the Yucatan micropig (YMP)
      porcine skin, and the use of IL/o MEs has been shown to dramatically increase ACV
      administration. Finally, the cytotoxicity of the new carrier was evaluated in
      vitro using the reconstructed human epidermal model LabCyteTM EPI-MODEL12. It was
      found that the cell viability of IL/o MEs containing 4wt% IL was over 80%
      compared to Dulbecco's Phosphate-Buffered Salines, indicating low cytotoxicity of
      the carrier. Taken together these results, it can be assumed that IL-assisted
      nonaqueous ME could serve as a versatile and efficient nanodelivery system for
      insoluble or sparingly soluble drug molecules that require solubilizing agents
      for delivery.

PMID- 20813175
TI  - Synthesis and in vitro/in vivo anti-cancer evaluation of curcumin-loaded
      chitosan/poly(butyl cyanoacrylate) nanoparticles.
AB  - We have synthesized novel cationic poly(butyl) cyanoacrylate (PBCA) nanoparticles
      coated with chitosan, formulation of curcumin nanoparticles. The size and zeta
      potential of prepared curcumin nanoparticles were about 200 nm and +29.11 mV,
      respectively with 90.04% encapsulation efficiency. The transmission electron
      microscopy (TEM) study revealed the spherical nature of the prepared
      nanoparticles along with confirmation of particle size. Curcumin nanoparticles
      demonstrate comparable in vitro therapeutic efficacy to free curcumin against a
      panel of human hepatocellular cancer cell lines, as assessed by cell viability (3
      [4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide assay [MTT assay]) and
      proapoptotic effects (annexin V/propidium iodide staining). In vivo, curcumin
      nanoparticles suppressed hepatocellular carcinoma growth in murine xenograft
      models and inhibited tumor angiogenesis. The curcumin nanoparticles' mechanism of
      action on hepatocellular carcinoma cells is a mirror that of free curcumin.

PMID- 20813176
TI  - Insight into glycyrrhetinic acid: the role of the hydroxyl group on liver
      targeting.
AB  - Two kinds of glycyrrhetinic acid-modified chitosan/poly(ethylene glycol)
      nanoparticles (CTS/PEG-GA NPs) were prepared by an ionic gelation process in
      which the liver targeting ligand glycyrrhetinic acid (GA) was introduced into the
      nanoparticles at the C(30)-carboxyl group (CTS/PEG-GA(c) NPs) or the C(3)
      hydroxyl group (CTS/PEG-GA(h) NPs). Their characteristics, especially their
      ability to target the liver, were compared. The results showed that both the
      CTS/PEG-GA(c) NPs and the CTS/PEG-GA(h) NPs are remarkably targeted to the liver.
      The accumulation in the liver is 51.3% and 56.5% of the injected dose for the
      CTS/PEG-GA(c)(4.60%) NPs (the subscript number denotes the GA content as weight
      percent in nanoparticles) and the CTS/PEG-GA(h)(4.57%) NPs at 3 h after
      injection, respectively. This is nearly 2.6-2.8 times higher than that obtained
      with the CTS/PEG NPs. According to our results, there is no significant
      difference between the CTS/PEG-GA(c) NPs and the CTS/PEG-GA(h) NPs in their
      ability to target the liver, when they were formed under identical conditions.
      This indicated that the C(3)-hydroxyl group in GA has little influence on the
      targeting ability.

PMID- 20813177
TI  - Lateral olivocochlear (LOC) neurons of the mouse LSO receive excitatory and
      inhibitory synaptic inputs with slower kinetics than LSO principal neurons.
AB  - We examined membrane properties and synaptic responses of neurons in the mouse
      lateral superior olivary nucleus (LSO). Two clear populations were identified
      consistent with: principal neurons which are involved in detecting interaural
      intensity differences (IIDs) and efferent neurons of the lateral olivocochlear
      (LOC) system which project to the cochlea. Principal neurons fired a short
      latency action potential (AP) often followed by an AP train during maintained
      depolarization. They possessed sustained outward K(+) currents, with little or no
      transient K(+) current (I(A)) and a prominent hyperpolarization-activated non
      specific cation conductance, I(H). On depolarization, LOC neurons exhibited a
      characteristic delay to the first AP. These neurons possessed a prominent
      transient outward current I(A), but had no I(H). Both LOC and principal neurons
      received glutamatergic and glycinergic synaptic inputs. LOC synaptic responses
      decayed more slowly than those of principal neurons; the mean decay time constant
      of AMPA receptor-mediated EPSCs was around 1 ms in principal neurons and 4 ms in
      LOC neurons. Decay time constants for glycinergic IPSCs were around 5 ms in
      principal neurons and 10 ms in LOC neurons. We conclude that principal cells
      receive fast synaptic responses appropriate for integration of IID inputs, while
      the LOC cells possess excitatory and inhibitory receptors with much slower
      kinetics.

PMID- 20813178
TI  - Response to Manley: an evolutionary perspective on middle ears.

PMID- 20813179
TI  - The flavonoid-rich fraction of Coreopsis tinctoria promotes glucose tolerance
      regain through pancreatic function recovery in streptozotocin-induced glucose
      intolerant rats.
AB  - AIM OF THE STUDY: Infusions of Coreopsis tinctoria Nutt. flowering tops have been
      used traditionally in Portugal to control hyperglycaemia and a previous study
      revealed that daily administration of the infusion during a 3-week period
      promoted the recovery of glucose tolerance by a mechanism different from
      inhibition of glucose absorption and direct promotion of insulin secretion. We
      know report the study of the ethyl acetate fraction of Coreopsis tinctoria
      flowers infusion aiming to confirm flavonoids as bioactive metabolites. To give
      one step forward into the antihyperglycaemic mechanism of action of this
      traditionally used plant we also studied the activity of Coreopsis tinctoria
      flavonoids on the pancreatic function of glucose-intolerant rats. A standard
      antioxidant, Trolox, was also studied for comparative purposes as the antioxidant
      mechanism has been frequently purposed as one of the mechanisms mediating
      antihyperglycaemic effects of flavonoid-rich extracts. MATERIAL AND METHODS:
      Thirteen compounds, mainly of flavanone and chalcone flavonoidal type, have been
      identified in this fraction by HPLC-DAD-ESI-MS/MS, and the major one (marein)
      quantified by HPLC-UV. The fraction (125 mg containing 20 mg of marein/kg b.w.)
      and Trolox (50 mg/kg b.w.) were administered daily by oral gavage to normal and
      STZ (40 mg/kg b.w.)-induced glucose-intolerant Wistar rats for 3 weeks. Blood
      glucose levels were measured weekly by Oral Glucose Tolerance Test. Pancreatic
      function was evaluated by plasma lipase of treated and non-treated glucose
      tolerant and- intolerant rats after the 3-week treatment period. RESULTS: After 2
      weeks oral treatment with Coreopsis tinctoria AcOEt fraction the animals were no
      longer glucose-intolerant, an effect maintained over the remaining experimental
      period. Additionally, plasma lipase values of glucose-intolerant animals treated
      with the AcOEt fraction (13.5 +/- 0.84 U/L) showed a clear reduction when
      compared with the glucose-intolerant group (34.60 +/- 1.76 U/L; P<0.001) and
      normoglycaemic control (8.35 +/- 0.69 U/L) demonstrating recovery of pancreatic
      function. On the other hand, treatment with standard antioxidant Trolox had no
      effect on glucose homeostasis of glucose-intolerant rats. The oral treatment with
      Coreopsis tinctoria fraction caused no hepatotoxicity, as determined by blood
      alanine and aspartate transaminases, and had also no effect on glucose
      homeostasis and pancreatic function of normal rats. CONCLUSIONS: AcOEt fraction,
      containing the same amount of marein as the infusion, promoted glucose tolerance
      regain in the rats more quickly, which means that the bioactivity is probably due
      to the several flavonoids present in Coreopsis tinctoria extracts and not to
      marein alone. The results also strongly suggest that these compounds act by
      promoting pancreatic cell function recovery from STZ-induced injury, possibly
      through a mechanism of action other than merely antioxidant mediated.

PMID- 20813180
TI  - Andrographolide and 14-deoxy-11,12-didehydroandrographolide from Andrographis
      paniculata attenuate high glucose-induced fibrosis and apoptosis in murine renal
      mesangeal cell lines.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Extracts of Andrographis paniculata Nees are used
      for various ethnomedical conditions including hyperglycemia and hypertension
      complications. AIM OF THE STUDY: The purpose of this study is to evaluate the
      anti-diabetic nephropathy effect of diterpene lactones andrographolide (AP1) and
      14-deoxy-11,12-didehydroandrographolide (AP2) from Andrographis paniculata.
      MATERIALS AND METHODS: MES-13, a SV40-transformed murine glomerular mesangial
      cell line, was cultured in high concentration of glucose to induce diabetic
      nephropathy phenotypes, which include secretion of extracellular matrix protein
      fibronectin, cytokine TGF-beta, states of oxidative stress, and apoptosis marker
      caspase-3. RESULTS: Our data suggest that addition of compounds AP1 or AP2
      reduces the phenotypes indicating diabetic nephropathy in MES-13 cells. The
      compound AP2 showed potent activity than AP1 in the reduction of apoptosis marker
      caspase-3, fibrosis marker TGF-beta, and PAI-1. Furthermore, AP1 and AP2 do not
      have antioxidant ability in acellular environment; however, addition of AP1 and
      AP2 reduced intracellular oxidative states in high glucose cultured MES-13 cells.
      CONCLUSION: This is the first report on anti-diabetic nephropathy effect of AP1
      and AP2 in part due to the regulation of intracellular signaling transduction,
      not mere clearance of reactive oxygen species. Thus, this study may be useful for
      drug development or food supplement for diabetes and nephropathy from
      Andrographis paniculata.

PMID- 20813181
TI  - Hypoglycemic effect of a leaf extract of Pseuderanthemum palatiferum (Nees)
      Radlk. in normal and streptozotocin-induced diabetic rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pseuderanthemum palatiferum (Nees) Radlk
      (Acanthaceae) was first found in Northern Vietnam and expanded throughout the
      country including the Mekong Delta region. The leaves of this plant are
      recommended in folk medicine of Vietnam and Thailand for promoting and treating
      various diseases including hypertension, diarrhea, arthritis, hemorrhoids,
      stomachache, tumors, colitis, bleeding, wounds, constipation, flu, colon cancer,
      nephritis, and diabetes. AIM OF THE STUDY: The hypoglycemic effect of an 80%
      ethanolic leaf extract from the leaves of Pseuderanthemum palatiferum (PPE) was
      investigated in normal and streptozotocin (STZ)-induced diabetic rats. MATERIALS
      AND METHODS: The PPE was administered daily and orally to the rats at the doses
      of 250, 500, and 1000 mg/kg body weight (b.w.) for 14 days. The levels of fasting
      plasma glucose (FPG), serum insulin, and biochemical data such as blood urea
      nitrogen (BUN), triglycerides (TG), total cholesterol (TC), high-density
      lipoprotein (HDL), low-density lipoprotein (LDL), and alkaline phosphatase (ALP)
      were evaluated. The hypoglycemic effect of PPE was compared to that of the known
      anti-diabetic drug glibenclamide (0.25 mg/kg b.w.). RESULTS: FPG and serum
      insulin in normal rats were not significantly different from the control and test
      groups in all dosages. The treated diabetic rats which had received PPE and
      glibenclamide showed significantly (p<0.05) decreased FPG and increased serum
      insulin levels at the end of the experiment. The hypoglycemic effect of PPE at
      the dose of 250 mg/kg b.w. was significantly (p<0.05) more effective than that of
      glibenclamide. The serum insulin in PPE fed diabetic rats at the dose of 250
      mg/kg b.w. was not different from those which had received glibenclamide, and
      this dose was significantly (p<0.05) more effective than PPE at the doses of 500
      and 1000 mg/kg b.w. while PPE increased HDL and decreased TC, TG, LDL, BUN and
      ALP in the diabetic rats. CONCLUSIONS: PPE has a beneficial effect in
      hyperglycemic rats and may prevent the complication of diabetes.

PMID- 20813182
TI  - Regulation of skeletal muscle transcriptome in elderly men after 6 weeks of
      endurance training at lactate threshold intensity.
AB  - A compromised muscle function due to aging, sarcopenia and reduced level of
      physical activity can lead to metabolic complications and chronic diseases.
      Endurance exercise counters these diseases by inducing beneficial adaptations
      whose molecular mechanisms remain unclear. We have investigated the
      transcriptomic changes following mild-intensity endurance training in skeletal
      muscle of elderly men. Seven healthy subjects followed an exercise program of
      cycle ergometer training at lactate threshold (LT) level for 60 min/day, five
      times/week during six weeks. Physiological and transcriptomic changes were
      analyzed before and after training. LT training decreased percentage body fat and
      fasting levels of plasma glucose, while increasing high-density lipoprotein
      cholesterol and lecithin-cholesterol acyltransferase levels. Transcriptomic
      analysis revealed fast-to-slow fiber type transition, increased amount of mtDNA
      encoded transcripts and modulation of 12 transcripts notably related to
      extracellular matrix (ECM), oxidative phosphorylation (OXPHOS), as well as
      partially characterized and novel transcripts. The training simultaneously
      induced the expression of genes related to slow fiber type transition, OXPHOS and
      ECM, which might contribute to the improvement of glucose and lipid metabolisms
      and whole body aerobic capacity.

PMID- 20813184
TI  - Roles of cAMP and cAMP-dependent protein kinase in the progression of prostate
      cancer: cross-talk with the androgen receptor.
AB  - Prostate carcinomas are among the most frequently diagnosed and death causing
      cancers affecting males in the developed world. It has become clear that the
      molecular mechanisms that drive the differentiation of normal prostate cells
      towards neoplasia involve multiple signal transduction cascades that often
      overlap and interact. A critical mediator of cellular proliferation and
      differentiation in various cells (and cancers) is the cAMP-dependent protein
      kinase, also known as protein kinase A (PKA), and its activating secondary
      messenger, cAMP. PKA and cAMP have been shown to play critical roles in prostate
      carcinogenesis and are the subject of this review. In particular we will focus on
      the cross-talk between PKA/cAMP signaling and that of the androgen receptor.

PMID- 20813185
TI  - A role for the cell cycle phosphatase Cdc25a in vitamin D-dependent inhibition of
      adult rat vascular smooth muscle cell proliferation.
AB  - We have explored the mechanism(s) underlying 1,25 dihydroxyvitamin D's
      (1,25(OH)(2)D) suppression of agonist-induced vascular smooth muscle cell (VSMC)
      proliferation. Quiescent cultured adult rat VSMC were treated with 1,25(OH)(2)D
      for 48h and endothelin (ET) or angiotensin II (AII) for the final 24h. We show
      that VSMC responded to 1,25(OH)(2)D or its less hypercalcemic analogue RO 25-6760
      with ~70% inhibition of ET-dependent (3)H-thymidine incorporation. The inhibition
      was linked to a comparable reduction in ET-stimulated cyclin-dependent kinase 2
      (Cdk2) activity and suppression of an ET-induced Cdk2 activator, cell division
      cycle 25 homolog A (Cdc25A). Both 1,25(OH)(2)D and RO 25-6760 completely
      inhibited the ET-dependent increase in Cdc25A mRNA and protein levels,
      phosphatase and promoter activities. 1,25(OH)(2)D also suppressed AII-induced DNA
      synthesis, Cdk2 activity and Cdc25A gene transcription. Inhibition of Cdc25A gene
      expression using a siRNA approach resulted in significant inhibition of ET or AII
      dependent Cdk2 activity and (3)H-thymidine incorporation. The Cdc25A siRNA
      mediated inhibition of ET or AII-induced Cdk2 activity and DNA synthesis was not
      additive with that produced by 1,25(OH)(2)D treatment. These data demonstrate
      that 1,25(OH)(2)D inhibits VSMC proliferation through a Cdc25A-dependent
      mechanism and suggest that this hormone may prove useful in the management of
      disorders characterized by aberrant proliferation of VSMC in the vascular wall.

PMID- 20813183
TI  - RNA granules: the good, the bad and the ugly.
AB  - Processing bodies (PBs) and Stress Granules (SGs) are the founding members of a
      new class of RNA granules, known as mRNA silencing foci, as they harbour
      transcripts circumstantially excluded from the translationally active pool. PBs
      and SGs are able to release mRNAs thus allowing their translation. PBs are
      constitutive, but respond to stimuli that affect mRNA translation and decay,
      whereas SGs are specifically induced upon cellular stress, which triggers a
      global translational silencing by several pathways, including phosphorylation of
      the key translation initiation factor eIF2alpha, and tRNA cleavage among others.
      PBs and SGs with different compositions may coexist in a single cell. These
      macromolecular aggregates are highly conserved through evolution, from
      unicellular organisms to vertebrate neurons. Their dynamics is regulated by
      several signaling pathways, and depends on microfilaments and microtubules, and
      the cognate molecular motors myosin, dynein, and kinesin. SGs share features with
      aggresomes and related aggregates of unfolded proteins frequently present in
      neurodegenerative diseases, and may play a role in the pathology. Virus
      infections may induce or impair SG formation. Besides being important for mRNA
      regulation upon stress, SGs modulate the signaling balancing apoptosis and cell
      survival. Finally, the formation of Nuclear Stress Bodies (nSBs), which share
      components with SGs, and the assembly of additional cytosolic aggregates
      containing RNA -the UV granules and the Ire1 foci-, all of them induced by
      specific cell damage factors, contribute to cell survival.

PMID- 20813186
TI  - The discovery of endothelin: the power of bioassay and the role of serendipity in
      the discovery of endothelium-derived vasocative substances.
AB  - Significant discoveries in biology and medicine are rare. The progress in these
      fields is predominantly incremental, but sometimes new observations revolutionize
      the field by opening new directions in research for decades to come. Two
      cornerstone observations in the late 1970s and early 1980s are examples of such
      "revolutionary" events. The first, by Furchgott and Zawadzki, was the discovery
      of the "obligatory role of the endothelium in vasorelaxation by acetylcholine".
      The other, by Hickey and colleagues, was the first description and
      characterization of a vasoconstrictor polypeptide produced by endothelial cells
      in culture. Both of these observations were achieved by the application of
      bioassay and serendipity played an important role in each of them. They both
      represent starting points for rapid growth in research activity world-wide
      leading to the identification of EDRF as nitric oxide, and the polypeptide EDCF
      as endothelin a few years later. These early observations also raised interest
      and initiated intensive R&D activity in the pharma industry culminating in the
      regulatory approval and marketing of novel medicines treating human diseases.
      This review describes the events leading to the discovery and early
      characterization of the peptidergic endothelium-derived constrictor factor, and
      its purification, sequencing and naming it endothelin.

PMID- 20813187
TI  - P2Y(13) receptor is responsible for ADP-mediated degranulation in RBL-2H3 rat
      mast cells.
AB  - Extracellular ADP is known to play many important physiological roles. In this
      study, we identified the P2Y(13) receptor in a rat mast cell line (RBL-2H3) and
      explored the functional role of ADP, its endogenous agonist. ADP induced both
      intracellular calcium mobilization and release of hexosaminidase (Hex). In an
      assay of intracellular calcium, ADP was 100-fold less potent than and equally
      efficacious as the P2Y(1) receptor-selective agonist MRS2365. However, ADP was
      more potent and efficacious than MRS2365 in inducing Hex release and in enhancing
      antigen-induced Hex release. ADP-induced intracellular calcium mobilization was
      blocked by phospholipase C inhibitor U73122 and by P2Y(1) receptor-selective
      antagonist MRS2500, but not by pertussis toxin (PTX), suggesting a mechanism
      mediated by the G(q)-coupled P2Y(1) receptor, but not P2Y(13) (G(i)-coupled) or
      P2X receptors. ADP-induced Hex release was blocked by PTX and a selective P2Y(13)
      receptor antagonist MRS2211, but not by MRS2500 or P2Y(1) receptor-specific
      siRNA, suggesting a G(i)-coupled P2Y(13) receptor-related mechanism. Measurement
      of gene expression confirmed high expression of both P2Y(1) and P2Y(13) receptors
      (in comparison to a previously reported P2Y(14) receptor) in RBL-2H3 cells. Thus,
      we demonstrated that ADP-mediated intracellular calcium mobilization and Hex
      release in RBL-2H3 cells are via P2Y(1) and P2Y(13) receptors, respectively.
      Selective antagonists of the P2Y(13) receptor might be novel therapeutic agents
      for various allergic conditions.

PMID- 20813188
TI  - Frontal phasic and oscillatory generators of the N30 somatosensory evoked
      potential.
AB  - The N30 component of somatosensory evoked potentials has been recognized as a
      crucial index of brain sensorimotor processing and has been increasingly used
      clinically. Previously, we have shown that the N30 is accompanied by both an
      increase of the power spectrum of the ongoing beta-gamma EEG (event related
      synchronization, ERS) and by a reorganization (phase-locking) of the spontaneous
      phase of this rhythm (inter-trials coherency, ITC). In order to localize its
      sources taking into account both the phasic and oscillatory aspects of the
      phenomenon, we here apply swLORETA methods on averaged signals of the event
      related potential (ERP) from a 128 scalp-electrodes array in time domain and also
      on raw EEG signals in frequency domain at the N30 peak latency. We demonstrate
      that the two different mechanisms that generate the N30 component power increase
      (ERS) and phase locking (ITC) across EEG trials are spatially localized in
      overlapping areas in the precentral cortex, namely the motor cortex (BA4) and the
      premotor cortex (BA6). From this common region, the generator of the N30 event
      related potential expands toward the posterior part of BA4, the anterior part of
      BA6 and the prefrontal cortex (BA9). These latter areas also present significant
      ITC sources in the beta-gamma frequency range, but without significant power
      increase of this rhythm. This demonstrates that N30 results from network activity
      that depends on distinct oscillating and phasic generators localized in the
      frontal cortex.

PMID- 20813189
TI  - Molecular systematics of the genus Holothuria in the Mediterranean and
      Northeastern Atlantic and a molecular clock for the diversification of the
      Holothuriidae (Echinodermata: Holothuroidea).
AB  - This work investigates the systematics of the genus Holothuria in the
      Mediterranean Sea and Northeastern Atlantic in the light of a wider molecular
      phylogenetic hypothesis of Holothuriidae, and it also provides a time-scale for
      the family diversification using mitochondrial markers and the molecular clock
      hypothesis. The subgenera Holothuria and Roweothuria are retrieved as
      paraphyletic. At least four separate lineages, with quite different time
      frameworks were identified. There are at least three species with an apparent
      long evolutionary history, H. forskali, H. sanctori and H. impatiens and six
      species belonging to Holothuria, Roweothuria and Vaneyothuria, which have
      diverged relatively recently.

PMID- 20813190
TI  - Late Miocene diversification and phylogenetic relationships of the huge toads in
      the Rhinella marina (Linnaeus, 1758) species group (Anura: Bufonidae).
AB  - We investigated the phylogeny and biogeography of the Rhinella marina group,
      using molecular, morphological, and skin-secretion data, contributing to an
      understanding of Neotropical faunal diversification. The maximum-parsimony and
      Bayesian analyzes of the combined data recovered a monophyletic R. marina group.
      Molecular dating based on Bayesian inferences and fossil calibration placed the
      earliest phylogenetic split within the R. marina group at ~ 10.47 MYA, in the
      late Miocene. Two rapid major diversifications occurred from Central Brazil,
      first northward (~ 8.08 MYA) in late Miocene and later southward (~ 5.17 MYA) in
      early Pliocene. These results suggest that barriers and dispersal routes created
      by the uplift of Brazilian Central Shield and climatic changes explain the
      diversification and current species distributions of the R. marina group.
      Dispersal-vicariance analyzes (DIVA) indicated that the two major
      diversifications of the R. marina group were due to vicariance, although eleven
      dispersals subsequently occurred.

PMID- 20813191
TI  - The origins of the giant pill-millipedes from Madagascar (Diplopoda:
      Sphaerotheriida: Arthrosphaeridae).
AB  - Giant pill-millipedes (order Sphaerotheriida) are large-bodied millipedes without
      poison glands which can roll-up into a complete ball. Their disconnected area of
      distribution spanning South Africa, Madagascar, India, SE Asia, Australia and New
      Zealand makes them interesting model organisms for biogeographic studies. The
      here presented phylogeny is based on a molecular dataset covering all areas of
      distribution with a special focus on Madagascar, where some species of giant pill
      millipedes show island gigantism, reaching the size of a baseball. For our study,
      two mitochondrial genes (partial 16S rRNA and COI) as well as the complete
      nuclear 18S rDNA were sequenced. While many recent vertebrate studies hint that
      the ancestors of the recent Malagasy fauna crossed the >350 km wide Mozambique
      Channel several times, no such crossing was discovered in the Sphaerotheriida.
      For the first time in a molecular phylogenetic study of soil arthropods, a
      Madagascar-India group, the family Arthrosphaeridae, is recovered, hinting to a
      Gondwanan origin of the Sphaerotheriida. The Malagasy-Indian family
      Arthrosphaeridae forms a monophyletic, statistically well-supported group in all
      obtained trees. The giant pill-millipedes from Madagascar are paraphyletic
      because the Malagasy genus Sphaeromimus is the sister-taxon of the Indian
      Arthrosphaera. In Sphaeromimus, an ecotone shift occurred only once: the spiny
      forest species Sphaeromimus musicus forms the sister-clade to the species
      collected in rainforests and littoral rainforests. The two species of the
      Malagasy genus Zoosphaerium which express island gigantism form a monophyletic
      group in some trees, but these trees lack good statistical support. Deeper nodes
      inside the Sphaerotheriida, like the position of the Australian genera
      Procyliosoma and Epicyliosoma, the Southeast Asian family Zephroniidae and the
      South African genus Sphaerotherium could not be resolved. This study is the first
      genetic study inside the order Sphaerotheriida and provides a proper basis for
      future molecular biogeographic studies in millipedes and soil organisms from
      Madagascar.

PMID- 20813192
TI  - Gene and species trees of a Neotropical group of treefrogs: genetic
      diversification in the Brazilian Atlantic Forest and the origin of a polyploid
      species.
AB  - The Neotropical Phyllomedusa burmeisteri treefrog group includes four diploid (P.
      bahiana, P. burmeisteri, P. distincta and P. iheringii) and one tetraploid (P.
      tetraploidea) forms. Here we use mitochondrial and nuclear sequence variation
      from across its range to verify if recognized morphospecies correspond to
      phylogenetic clades, examine the origin of the polyploid P. tetraploidea, and
      compare range wide patterns of diversification to those of other BAF organisms.
      We compared single gene trees with one Bayesian multi-gene tree, and one Bayesian
      species tree inferred under a coalescent framework. Our mtDNA phylogenetic
      analyses showed that P. bahiana, P. burmeisteri and P. iheringii correspond to
      monophyletic clades, while P. distincta and P. tetraploidea were paraphyletic.
      The nuclear gene trees were concordant in revealing two moderately supported
      groups including (i) P. bahiana and P. burmeisteri (northern species) and (ii) P.
      distincta, P.tetraploidea and P. iheringii (southern species). The multi-gene
      tree and the species tree retrieved similar topologies, giving high support to
      the northern and southern clades, and to the sister-taxa relationship between P.
      tetraploidea and P. distincta. Estimates of (t)MRCA suggest a major split within
      the P. burmeisteri group at ~ 5 Myr (between northern and southern groups), while
      the main clades were originated between ~ 0.4 and 2.5 Myr, spanning the late
      Pliocene and Pleistocene. Patterns of geographic and temporal diversification
      within the group were congruent with those uncovered for other co-distributed
      organisms. Independent paleoecological and geological data suggest that
      vicariance associated with climatic oscillations and neotectonic activity may
      have driven lineage divergence within the P. burmeisteri group. P. tetraploidea
      probably originated from polyploidization of P. distincta or from a common
      ancestor.

PMID- 20813193
TI  - Species delimitation in the Central African herbs Haumania (Marantaceae) using
      georeferenced nuclear and chloroplastic DNA sequences.
AB  - Species delimitation is a fundamental biological concept which is frequently
      discussed and altered to integrate new insights. These revealed that speciation
      is not a one step phenomenon but an ongoing process and morphological characters
      alone are not sufficient anymore to properly describe the results of this
      process. Here we want to assess the degree of speciation in two closely related
      lianescent taxa from the tropical African genus Haumania which display distinct
      vegetative traits despite a high similarity in reproductive traits and a partial
      overlap in distribution area which might facilitate gene flow. To this end, we
      combined phylogenetic and phylogeographic analyses using nuclear (nr) and
      chloroplast (cp) DNA sequences in comparison to morphological species
      descriptions. The nuclear dataset unambiguously supports the morphological
      species concept in Haumania. However, the main chloroplastic haplotypes are
      shared between species and, although a geographic analysis of cpDNA diversity
      confirms that individuals from the same taxon are more related than individuals
      from distinct taxa, cp-haplotypes display correlated geographic distributions
      between species. Hybridization is the most plausible reason for this pattern. A
      scenario involving speciation in geographic isolation followed by range expansion
      is outlined. The study highlights the gain of information on the speciation
      process in Haumania by adding georeferenced molecular data to the morphological
      characteristics. It also shows that nr and cp sequence data might provide
      different but complementary information, questioning the reliability of the
      unique use of chloroplast data for species recognition by DNA barcoding.

PMID- 20813194
TI  - Mechanical impact induces cartilage degradation via mitogen activated protein
      kinases.
AB  - OBJECTIVE: To determine the activation of Mitogen activated protein (MAP) kinases
      in and around cartilage subjected to mechanical damage and to determine the
      effects of their inhibitors on impaction-induced chondrocyte death and cartilage
      degeneration. DESIGN: The phosphorylation of MAP kinases was examined with
      confocal microscopy and immunoblotting. The effects of MAP kinase inhibitors on
      impaction-induced chondrocyte death and proteoglycan (PG) loss were determined
      with fluorescent microscopy and 1, 9-Dimethyl-Methylene Blue (DMMB) assay. The
      expression of catabolic genes at mRNA levels was examined with quantitative real
      time PCR. RESULTS: Early p38 activation was detected at 20 min and 1h post
      impaction. At 24h, enhanced phosphorylation of p38 and extracellular signal
      regulated protein kinase (ERK)1/2 was visualized in chondrocytes from in and
      around impact sites. The phosphorylation of p38 was increased by 3.0-fold in
      impact sites and 3.3-fold in adjacent cartilage. The phosphorylation of ERK-1 was
      increased by 5.8-fold in impact zone and 5.4-fold in adjacent cartilage; the
      phosphorylation of ERK-2 increased by 4.0-fold in impacted zone and 3.6-fold in
      adjacent cartilage. Furthermore, the blocking of p38 pathway did not inhibit
      impaction-induced ERK activation. The inhibition of p38 or ERK pathway
      significantly reduced injury-related chondrocyte death and PG losses.
      Quantitative Real-time PCR analysis revealed that blunt impaction significantly
      up-regulated matrix metalloproteinase (MMP)-13, Tumor necrosis factor (TNF)
      alpha, and ADAMTS-5 expression. CONCLUSION: These findings implicate p38 and ERK
      mitogen activated protein kinases (MAPKs) in the post-injury spread of cartilage
      degeneration and suggest that the risk of post-traumatic osteoarthritis (PTOA)
      following joint trauma could be decreased by blocking their activities, which
      might be involved in up-regulating expressions of MMP-13, ADAMTS-5, and TNF
      alpha.

PMID- 20813195
TI  - Alignment of the medial tibial plateau affects the rate of joint space narrowing
      in the osteoarthritic knee.
AB  - OBJECTIVE: To determine, in serial fixed-flexion (FF) radiographs of subjects
      with knee osteoarthritis (KOA), the importance of, and basis for, the effect of
      alignment of the medial tibial plateau (MTP), as determined by the inter-margin
      distance (IMD), on joint space narrowing (JSN). METHODS: Baseline and 12-month X
      rays of 590 knees with Kellgren and Lawrence grade (KLG) 2/3 OA from the public
      release dataset of the Osteoarthritis Initiative (OAI) were assigned to subgroups
      based upon IMD at baseline (IMD(BL)) and the difference between IMD(BL) and
      IMD(12 mos). Relationships of JSN to IMD(BL) and to the difference between IMD(BL
      and) IMD(12 mos) were evaluated. RESULTS: In all 590 knees, mean JSN was 0.13 +/-
      0.51 mm (P<0.0001) and MTP alignment and replication of IMD(BL) in the 12-month
      film were, in general, poor. JSN was significantly (P=0.012) more rapid in
      Subgroup A (IMD<=1.70 mm at both time points) than in Subgroup B (both IMDs>1.70
      mm): 0.15 +/- 0.43; 0.08 +/- 0.47. Within Subgroup B we identified a subset,
      Subgroup B1, in which, although alignment was poor at both time points, the large
      IMD(BL) was, by chance, highly reproduced by IMD(12 mos) (difference between the
      two IMDs=0.01 +/- 0.27 mm, NS). JSN in Subgroup B1 was 0.06 +/- 0.41 mm and did
      not differ from that in other knees of Subgroup B (P=0.87). The standardized
      response mean (SRM) in all 590 knees and Subgroups A, B and B1 was 0.25, 0.34,
      0.17 and 0.06, respectively. Independent of IMD(BL), JSN correlated significantly
      with the difference between the IMDs in the two radiographs (r=0.17, P=0.0001).
      CONCLUSION: Skewed MTP alignment in serial films and poor replication of IMD(BL)
      in the follow-up exam affect JSN measurement. The magnitude of change in joint
      space width (JSW) related to the poor quality of alignment that is common with
      the FF view jeopardizes accurate evaluation of JSN.

PMID- 20813196
TI  - Fusobacterium necrophorum bacteremic tonsillitis: 2 Cases and a review of the
      literature.
AB  - Fusobacterium necrophorum can cause endemic pharyngitis and the Lemierre
      syndrome. Four previous case reports and one epidemiologic study have documented
      that some F. necrophorum pharyngitis patients develop bacteremia without
      developing the complete Lemierre syndrome. We report two more patients who have
      bacteremic F. necrophorum pharyngitis. We summarize the clinical presentation of
      these six patients. All received early diagnosis and excellent response to
      antibiotics. We speculate that prompt antibiotic treatment may have prevented the
      more serious Lemierre syndrome. Adolescents and young adults who present with
      significant pharyngotonsillitis and bacteremic symptoms should have blood
      cultures and receive antibiotic regimens that treat F. necrophorum. Recognition
      of such patients might prevent Lemierre syndrome.

PMID- 20813198
TI  - Cost and clinical analysis of autologous hematopoietic stem cell mobilization
      with G-CSF and plerixafor compared to G-CSF and cyclophosphamide.
AB  - Plerixafor plus granulocyte-colony stimulating factor (G-CSF) has been shown to
      mobilize more CD34(+) cells than G-CSF alone for autologous hematopoietic stem
      cell transplantation (HSCT). However, many centers use chemotherapy followed by G
      CSF to mobilize CD34(+) cells prior to HSCT. We performed a retrospective study
      of patients who participated in the expanded access program (EAP) of plerixafor
      and G-CSF for initial mobilization of CD34(+) cells, and compared outcomes to
      matched historic controls mobilized with cyclophosphamide 3-5 g/m(2) and G-CSF at
      2 centers that participated in the EAP Control patients were matched for age,
      sex, disease, disease stage, and number of prior therapies. Mobilization costs
      were defined to be the costs of medical procedures, resource utilization, and
      medications. Median national CMS reimbursement rates were used to establish the
      costs of procedures, hospitalization, provider visits, apheresis, CD34(+) cell
      processing and cryopreservation. Average sale price was used for G-CSF,
      plerixafor, cyclophosphamide, MESNA, antiemetics, and antimicrobials. A total of
      33 patients from the EAP and 33 matched controls were studied. Two patients in
      the control group were hospitalized for neutropenic fever during the mobilization
      period. Apheresis started on the scheduled day in 33 (100%) study patients and in
      29 (88%) control patients (P = 0.04). Sixteen (48%) control patients required
      weekend apheresis. There was no difference in number of CD34(+) cells collected
      between the groups, and all patients proceeded to HSCT with no difference in
      engraftment outcomes. Median total cost of mobilization was not different between
      the plerixafor/G-CSF and control groups ($14,224 versus $18,824; P = .45). In
      conclusion, plerixafor/G-CSF and cyclophosphamide/G-CSF for upfront mobilization
      of CD34(-) cells resulted in similar numbers of cells collected, costs of
      mobilization, and clinical outcomes. Additionally, plerixafor/G-CSF mobilization
      resulted in more predictable days of collection, no weekend apheresis procedures,
      and no unscheduled hospital admissions.

PMID- 20813197
TI  - Unrelated donor bone marrow transplantation for myelodysplastic syndrome in
      children.
AB  - We describe long-term disease-free survival (DFS) after unrelated donor bone
      marrow transplantation (BMT) for myelodysplastic syndrome (MDS) in 118 patients
      aged <=18 years. Forty-six patients had refractory cytopenia (RC), 55 refractory
      anemia with excess blasts (RAEB), and 17 refractory anemia with excess blasts in
      transformation (RAEB-t). Transplant-related mortality was higher after mismatched
      BMT (relative risk [RR] 3.29, P = .002). Disease recurrence was more likely with
      advanced stages of MDS at the time of BMT: RAEB (RR 6.50, P = .01) or RAEB-t (RR
      11.00, P = .004). Treatment failure (recurrent disease or death from any cause;
      inverse of DFS) occurred in 68 patients. Treatment failure was higher after
      mismatched BMT (RR 2.79, P = .001) and in those with RAEB-t (RR 2.38, P = .02).
      Secondary MDS or chemotherapy prior to BMT was not associated with recurrence or
      treatment failure. Similarly, cytogenetic abnormalities were not associated with
      transplant outcomes. Eight-year DFS for patients with RC after matched and
      mismatched unrelated donor BMT was 65% and 40%, respectively. Corresponding DFS
      for patients with RAEB and RAEB-t was 48% and 28%, respectively. When a matched
      adult unrelated donor is available, BMT should be offered as first-line therapy,
      and children with RC can be expected to have the best outcome.

PMID- 20813199
TI  - Platelet and red blood cell utilization and transfusion independence in umbilical
      cord blood and allogeneic peripheral blood hematopoietic cell transplants.
AB  - Allogeneic hematopoietic cell transplantation (HCT) recipients have substantial
      transfusion requirements. Factors associated with increased transfusions and the
      extent of blood product use in umbilical cord blood (UCB) recipients are
      uncertain. We reviewed blood product use in 229 consecutive adult recipients of
      allogeneic HCT at the University of Minnesota: 147 with leukemia, 82 lymphoma or
      myeloma; 58% received unrelated UCB and 43% sibling donor peripheral blood stem
      cell (PBSC) grafts. Although neutrophil recovery was prompt (UCB median 17,
      range: 2-45 days, and PBSC 14, range: 3-34 days), only 135 of 229 (59% cumulative
      incidence) achieved red blood cell (RBC) independence and 157 (69%) achieved
      platelet independence by 6 months. Time to platelet independence was prolonged in
      UCB recipients (median UCB 41 versus PBSC 14 days) and in patients who had
      received a prior transplant (median 48 versus 32 days). Patients who received UCB
      grafts required more RBC through day 60 post-HCT (mean UCB 7.8 (95% confidence
      interval [CI] 6.7-8.9) versus PBSC 5.2 (3.7-6.7) transfusions, P = .04), and more
      platelet transfusions (mean 25.2 (95% CI 22.1-28.2) versus 12.9 (9.4-16.4), P <
      .01) compared to PBSC recipients. Patients receiving myeloablative (MA)
      conditioning required more RBC and platelet transfusions during the first 2
      months post-HCT compared to reduced-intensity conditioning (RIC) (7.4 versus 6.2,
      P = .30 for RBC; 23.2 versus 17.5, P = .07 for platelets). Despite prompt
      neutrophil engraftment, UCB recipients had delayed platelet recovery as well as
      more prolonged and costly blood product requirements. Enhanced approaches to
      accelerate multilineage engraftment could limit the transfusion-associated
      morbidity and costs accompanying UCB allotransplantation.

PMID- 20813201
TI  - Mechanisms of TNFalpha regulation in uveitis: focus on RNA-binding proteins.
AB  - Tumour necrosis factor-alpha (TNFalpha) is a key mediator of inflammation and
      plays a crucial role during the early phase of a host's defence against
      bacterial, viral and parasitic infections. Persistent production of TNFalpha
      occurs in many autoimmune inflammatory diseases, including uveitis, and this is
      associated with significant tissue damage. Although uveitis represents a
      phenotypically heterogeneous group of intraocular inflammatory conditions, they
      have in common raised levels of TNFalpha in both serum and aqueous humour.
      Supporting a critical role for TNF activity during uveitis are reports that serum
      levels of TNFalpha correlate with disease status as well as the increasing
      evidence of therapeutic success of anti-TNF agents. TNFalpha is an archetypal
      pleiotropic cytokine and when acting systemically acute release may cause
      profound physiological decompensation. Yet, conversely, at tissue sites TNFalpha
      plays important roles governing homeostasis and during chronic inflammation
      regulating immune responses through control of, for example, macrophage-T cell
      functions. In a murine model of CD4(+) T cell mediated non-infectious uveitis,
      experimental autoimmune uveitis (EAU), activation of infiltrating macrophages
      mediates tissue damage. In EAU, whilst both T cells and macrophages generate
      TNFalpha, tissue damaging macrophage activation is dependent upon TNF receptor 1
      (p55). TNFalpha protein production is controlled at the level of transcription,
      pre-mRNA processing, mRNA stability, translation and retention at the plasma
      membrane. The p38 MAP kinase and MAPKAP-2 pathway are involved in the post
      transcriptional regulation of TNFalpha and are targeted by a functionally
      divergent group of cytokines including IL-10 and TGFbeta1. Common to many
      cytokines, TNFalpha mRNA 3' untranslated region (UTR) contains an AU-rich element
      (ARE), which drives repression by mRNA-binding proteins (RBPs). These include
      tristetraprolin (TTP), T cell antigen-1 (TIA-1), TIA-1-related protein (TIAR),
      human antigen R (HuR) and fragile-X-related protein 1 (FXR1). Disruption of
      several RBPs can dysregulate TNFalpha protein production and has, in some cases,
      been shown to exacerbate chronic inflammatory disease both in mice and in humans.
      Given that TNFalpha is central to clearance of infections, yet during chronic
      inflammation results in tissue damage, understanding the role that RBPs play in
      the control of TNFalpha may give rise to opportunities to not only develop
      targeted therapy for autoimmunity but also redress homeostasis without compromise
      and risking infection. The study of mRNA stability remains essential for the
      understanding of intracellular regulatory pathways and molecular mechanisms of
      pathology for infection, inflammation and degeneration.

PMID- 20813202
TI  - What is the value of human FMRI in CNS drug development?
AB  - Functional neuroimaging has the potential to improve the decision-making process
      in the development of new drugs. With the high cost of failure of compounds in
      later stages of development, there is a need to establish, early in man, reliable
      measures of drug activity and efficacy in the brain. Functional magnetic
      resonance imaging (FMRI) is a tool for serially examining normal and pathological
      brain function at the systems level. FMRI is helping us to understand therapeutic
      mechanisms and can provide clinically relevant markers of disease responses to
      drugs. An analysis of the value of FMRI to aid decision-making requires an
      appreciation of the techniques and their validation, a task that has begun and
      which necessitates an investment of its own.

PMID- 20813200
TI  - EGFR signaling in breast cancer: bad to the bone.
AB  - The epidermal growth factor receptor (EGFR) is a member of the ErbB family of
      receptor tyrosine kinases. This family includes EGFR/ErbB1/HER1, ErbB2/HER2/Neu
      ErbB3/HER3, and ErbB4/HER4. For many years it was believed that EGFR plays a
      minor role in the development and progression of breast malignancies. However,
      recent findings have led investigators to revisit these beliefs. Here we will
      review these findings and propose roles that EGFR may play in breast
      malignancies. In particular, we will discuss the potential roles that EGFR may
      play in triple-negative tumors, resistance to endocrine therapies, maintenance of
      stem-like tumor cells, and bone metastasis. Thus, we will propose the contexts in
      which EGFR may be a therapeutic target.

PMID- 20813204
TI  - Mitochondria and viruses.
AB  - Mitochondria are involved in a variety of cellular metabolic processes, and their
      functions are regulated by extrinsic and intrinsic stimuli including viruses.
      Recent studies have shown that mitochondria play a central role in the primary
      host defense mechanisms against viral infections, and a number of novel viral and
      mitochondrial proteins are involved in these processes. Some viral proteins
      localize in mitochondria and interact with mitochondrial proteins to regulate
      cellular responses. This review summarizes recent findings on the functions and
      roles of these molecules as well as mitochondrial responses to viral infections.

PMID- 20813203
TI  - PKG-I inhibition attenuates vascular endothelial growth factor-stimulated
      angiogenesis.
AB  - Vascular endothelial growth factor (VEGF) stimulates nitric oxide (NO)
      production, which mediates many of its angiogenic actions. However, the
      angiogenic pathways that operate downstream of NO following VEGF treatment are
      not well characterized. Herein, we used DT-2 and DT-3, two highly selective cGMP
      dependent protein kinase I peptide inhibitors to determine the contribution of
      PKG-I in VEGF-stimulated angiogenesis. Incubation of chicken chorioallantoic
      membranes (CAM) with PKG-I peptide inhibitors decreased vascular length in a dose
      dependent manner, with DT-3 being more effective than DT-2. Moreover, inhibition
      of PKG-I with DT-3 abolished the angiogenic response elicited by VEGF in the
      rabbit eye cornea. PKG-I inhibition also blocked VEGF-stimulated vascular
      leakage. In vitro, treatment of cells with VEGF stimulated phosphorylation of the
      PKG substrate VASP through VEGFR2 activation; the VEGF-stimulated VASP
      phosphorylation was reduced by DT-2. Pre-treatment of cells with DT-2 or DT-3
      inhibited VEGF-stimulated mitogen-activated protein kinase cascades (ERK1/2 and
      p38), growth, migration and sprouting of endothelial cells. The above
      observations taken together identify PKG-I as a downstream effector of VEGFR2 in
      EC and provide a rational basis for the use of PKG-I inhibitors in disease states
      characterized by excessive neovascularization.

PMID- 20813205
TI  - A novel mutation in the mitochondrial tRNA(Ala) gene (m.5636T>C) in a patient
      with progressive external ophthalmoplegia.
AB  - We report a heteroplasmic novel mutation m.5636T>C in the mt-tRNA(Ala) in a
      patient with bilateral ptosis and ophthalmoparesis in whom a muscle biopsy showed
      cytochrome c oxdidase (COX) negative and ragged red fibers. Using laser capture
      microdissection we have isolated COX negative fibers and COX positive fibers from
      the muscle of the patient and determined that the mutation load was clearly
      increased in COX negative muscle fibers. Additionally, the mutated m.5636T
      nucleotide is conserved in all the mammal and non-mammal species analyzed and
      might be structurally relevant as it is located in a position involved in the
      formation of tertiary structure of canonical mitochondrial tRNAs.

PMID- 20813206
TI  - Overview of Chinese research on senile dementia in mainland China.
AB  - Studies of senile dementia (SD) on the Chinese mainland, done over the decades,
      have furthered the understanding of its epidemiology, basic and clinical medical
      aspects, and effects on health economics, to name a few areas. There are 6-7
      million Chinese people with SD, with an incidence of 5-7% of people over 65 years
      of age. In this group, Alzheimer's accounts for 50-60% of SD. The pathogenesis of
      Alzheimer's disease has been investigated, and known risk factors include beta
      amyloid, formaldehyde, acetyl cholinesterase, inflammation, neuronal dysfunction
      and death. Mild cognitive impairment (MCI) is an independent risk factor of SD.
      Comprehensive treatment can improve clinical efficacy, and quality of life can be
      improved by appropriate and reasonable care and rehabilitation therapy. However,
      swallowing disorders, infection and systemic failure remain the main causes of
      death among SD patients. In the Chinese mainland, SD extracts a total annual
      economic loss of 83.5-97.4 billion yuan and is responsible for 51.3-59.8 billion
      yuan in annual healthcare costs. Despite the progress to date, basic research and
      drug development for SD are needed. Also, a more evidence-based approach to
      Chinese medicine research would be prudent. Such research results can hopefully
      provide valuable cues for governmental decision-making and assist in addressing
      and halting the incidence of SD in China.

PMID- 20813207
TI  - SLE diagnosis and treatment: when early is early.
AB  - Around 1980 antinuclear antibody testing became widely used in routine laboratory
      practice leading to a tapering in the lag time between SLE onset and diagnosis.
      Since then nothing relevant has been introduced which could help us in making the
      diagnosis of SLE earlier than now. Notably, there is increasing evidence that
      early diagnosis and treatment could increase SLE remission rate and improve
      patient prognosis. Although it has been shown that autoantibodies appear before
      clinical manifestations in SLE patients, currently we cannot predict which
      autoantibody positive subjects will eventually develop the disease. Thus, great
      effort should be made in order to identify new biomarkers able to improve our
      diagnostic potential. B lymphocyte stimulator (BLyS), anti-ribosomal P protein
      and anti-C1q antibodies are among the most promising. In recent years, some
      therapeutic options have emerged as appropriate interventions for early SLE
      treatment, including antimalarials, vitamin D, statins and vaccination with self
      derived peptides. All these immune modulators seem to be particularly useful when
      introduced in an early stage of the disease.

PMID- 20813208
TI  - Development of novel nanoparticles shelled with heparin for berberine delivery to
      treat Helicobacter pylori.
AB  - Various approaches have been proposed to overcome the unpleasant side-effects
      associated with antibiotic treatment for Helicobacter pylori. The limited
      effectiveness of such approaches has forced researchers to consider alternative
      strategies to eliminate H. pylori infection. The plant alkaloid berberine is
      known to significantly reduce proliferation of H. pylori. To localize berberine
      to the site of H. pylori infection, this study developed a novel nanoparticle
      berberine carrier with a heparin shell. Analysis of a simulated gastrointestinal
      medium indicated that the proposed in vitro drug carrier system effectively
      controlled the release of berberine, which interacted specifically with the
      intercellular space at the site of H. pylori infection. Furthermore, the prepared
      nanoparticles significantly increased the suppressive effect of berberine on H.
      pylori growth while efficiently reducing cytotoxic effects in H. pylori-infected
      cells.

PMID- 20813209
TI  - A hydrotropic beta-cyclodextrin grafted hyperbranched polyglycerol co-polymer for
      hydrophobic drug delivery.
AB  - The development of successful formulations for poorly water soluble drugs remains
      a longstanding, critical, and challenging issue in cancer therapy. A beta
      cyclodextrin (CD) functionalized hyperbranched polyglycerol (HPG) has been
      prepared as a potential water insoluble drug carrier. The HPG-g-CD molecules
      could self-assemble into multimolecular spherical micelles in water, the size of
      which ranged from 200 to 300 nm, with good dispersity. A high loading capacity
      and high encapsulation efficiency of paclitaxel, as a model, were obtained. The
      release profiles of different co-polymer compositions showed a burst release
      followed by continuous extended release. Furthermore, MTT analysis showed that
      HPG-g-CD had good biocompatibility, indicating that HPG-g-CD may be considered a
      promising hydrophobic drug delivery system.

PMID- 20813210
TI  - Determination of the deletion breakpoints in two patients with contiguous gene
      syndrome encompassing CYBB gene.
AB  - X-linked chronic granulomatous disease is a primary immunodeficiency caused by
      mutations in CYBB. Although large deletions involving CYBB are known to cause
      contiguous gene syndrome (CGS), only a few patients have been studied precisely
      at the molecular levels. Our study determined the deletion breakpoints in two
      patients with CGS involving CYBB by array comparative genomic hybridization and
      the following PCR and DNA walking studies. The deletion size was 3.5 Mb in
      Patient 1 and 0.8 Mb in Patient 2. There were no homologous architectural
      features between the telomeric and centromeric breakpoint junctions in the
      deletions of either patient. However, the telomeric breakpoint of Patient 2 was
      embedded in a stretch of low-copy repeats and the centromeric breakpoint was also
      embedded in a stretch of short segments with significant sequence homology. These
      findings suggest the potential involvement of genome architecture in stimulating
      genomic rearrangements in Patient 2.

PMID- 20813211
TI  - Mosaic microdeletion 18q21 as a cause of mental retardation.
AB  - We present the clinical and cytogenetic findings in an 8 year old girl with
      mental retardation, acquired microcephaly, delayed motor skills and stereotypical
      hand movements. Array comparative genomic hybridization identified a mosaic de
      novo deletion of approximately 7.505 Mb in chromosome region 18q21.1q21.31,
      resulting in the loss of one copy of the TCF4 gene as well as 29 other RefSeq
      genes. The deletion likely occurred early in development as this child has
      clinical symptoms affecting multiple organ systems, reminiscent of those observed
      in Pitt-Hopkins syndrome (PHS; OMIM 610954). This case represents the second
      known example of a mosaic deletion resulting in clinical symptoms consistent with
      Pitt-Hopkins syndrome, and illustrates the utility of genomic microarray analysis
      in detecting large mosaic imbalances that may otherwise be missed by G-band
      analysis.

PMID- 20813212
TI  - Duplication of the TGFBR1 gene causes features of Loeys-Dietz syndrome.
AB  - Loeys-Dietz syndrome (LDS; OMIM:609192) is an autosomal dominant disorder
      characterized by hypertelorism, bifid uvula or cleft palate, and arterial
      tortuosity with widespread vascular aneurysms and a high risk of aortic
      dissection at an early age. LDS results from mutations in the transforming growth
      factor beta-receptor I and II (TGFBR1 and TGFBR2) genes, altering the
      transmission of the subcellular TGF-beta signal, mediated by increased activation
      of Smad2. We report on a 17-year-old boy with pubertas tarda, a bifid uvula,
      camptodactyly and facial dysmorphic features, suggestive of LDS. Mutation
      analysis of TGFBR1 and TGFBR2 was normal. By means of molecular karyotyping two
      previously unreported chromosomal imbalances were detected: a 120 kb deletion on
      chromosome 22q13.31q13.32, inherited from an unaffected parent, and a de novo
      14.6 Mb duplication on chromosome 9q22.32q31.3, comprising TGFBR1. We hypothesize
      that copy number gain of TGFBR1 contributes to the phenotype.

PMID- 20813213
TI  - Noah's nectar: the proteome content of a glass of red wine.
AB  - Combinatorial peptide ligand libraries (CPLLs) have been adopted for harvesting
      and identifying traces of proteins present in red wines. Surprisingly, although
      it is stated that red wines are in general fined with egg albumin, for all
      Italian wines investigated (in the areas around Chiari and Verona as well as in
      the Chianti area) we find that the only fining agent used is bovine casein, just
      like in white wines. Although the typical levels of casein found range between 45
      to 85MUg/L, in one case as little as 3.8MUg/L of casein could be detected, an
      extremely high level of sensitivity, close to our lower detection limit of 1MUg/L
      reported for white wines. As a result of such treatments, very small amounts of
      residual proteins in red wines could be identified: essentially no residual grape
      proteins (except for thaumatin), but only traces of proteins from Saccharomyces
      cerevisiae and a few proteins from plant pathogens and fungi (e.g., Botryotinia
      fuckeliana, Sclerotinia sclerotiorum, Aspergillus aculeatus). Contrary to what
      has been found in white wines, the best capture efficiency with CPLLs has
      occurred at pH 7.2 and pH 9.3, with minimal capture at pH 3.3. The fact that such
      very low levels of fining agents can still be detected in treated red wines
      should be taken into consideration by winemakers in labelling their products and
      by EC rulers in issuing proper regulations.

PMID- 20813214
TI  - Proteasome and oxidative phoshorylation changes may explain why aging is a risk
      factor for neurodegenerative disorders.
AB  - Neurodegenerative disorders (ND) belong to the most devastating diseases in the
      industrialized western world. Alzheimer disease (AD) is the most prevalent among
      these disorders followed by Parkinson disease (PD). Huntington disease (HD) is an
      autosomal dominantly inherited condition with a single mutation that causes
      disease in almost 100% of all cases. In this review we used previously published
      proteomics studies on AD, PD and HD to find cellular pathways changed similarly
      in ND and aging. All studies employed large gel two dimensional gel
      electrophoresis for protein separation and mass spectrometry for protein
      identification. Altered proteins were subjected to a KEGG pathway analysis and
      altered pathways determined for each disorder and aging. We found that besides
      the mitochondrial oxidative phosphorylation, the proteasome system are altered in
      aging and ND. The proteasome facilitates protein degradation which is commonly
      perturbed in ND which may link neurodegeneration to its largest risk factor
      aging.

PMID- 20813215
TI  - Rabbit cortical bone tissue increases its elastic stiffness but becomes less
      viscoelastic with age.
AB  - Bone is dynamic tissue undergoing changes in its composition, structure and
      functional properties during growth. It has been proposed that especially changes
      in the collagen phase of bone are responsible for making the bone more fragile,
      and potentially less viscoelastic with age. Hence, robust methods to measure
      viscoelasticitiy are needed. This study aimed to characterize the development of
      the elastic and viscoelastic mechanical properties of rabbit bone during
      maturation and growth, as assessed by nanoindentation. The humeri from female New
      Zealand white rabbits of varying age (newborn, 11 days, 4 weeks, 3 and 6 months
      old, n=8 per group) were investigated. Mid-diaphyseal cortical bone samples were
      cut, dehydrated, embedded and polished. Nanoindentation probing, semi-dynamic
      testing with a frequency of 20 Hz and creep with a dwell time of 60 s were
      performed under load control to quantify the elastic and the time-dependent
      viscoelastic mechanical properties of bone. The elastic moduli were evaluated
      with all three methods and the viscoelastic parameters were assessed using the
      phase-shift and the creep time constant. The elastic stiffness of bone increased
      significantly with each consecutive age group, from 11 days to 6 months of age,
      based on the reduced modulus from the indentation probing, the storage modulus
      from the semi-dynamic test, and the first elastic parameter from the creep test.
      These elastic parameters correlated significantly (R=0.88-0.94, p<0.01). The
      values of viscoelastic parameters, the phase-shift and time creep constant,
      decreased significantly with age. The viscous properties determined by the creep
      and the semi-dynamic testing correlated significantly (R=0.90, p<0.01), however,
      no correlation was found between the phase-shift and the creep time constant.
      Additionally, the present results showed specific associations with tissue
      composition, as measured with Fourier Transform Infrared spectroscopy of the same
      samples. In summary, the present results reveal significant changes in material
      properties of rabbit cortical bone with age. The elastic modulus of bone tissue
      increased by approximately 60%, whereas the viscoelastic parameters decreased by
      10% to 25% during the first 6 months of the rabbit's life. Together, this
      indicates significant structural and functional maturation of the bone matrix
      during growth of the rabbit.

PMID- 20813216
TI  - Associations between amino acids and bone mineral density in men with idiopathic
      osteoporosis.
AB  - Idiopathic osteoporosis in middle-aged men is characterized by low-level bone
      formation. Inhibited anabolism may be involved in the pathogenesis of the disease
      and amino acids may be of importance. In the present study fasting amino acid
      profiles in plasma and erythrocytes were determined in 22 male idiopathic
      osteoporosis (MIO) patients and in 20 age-matched healthy men and associated with
      bone mineral density, bone histomorphometry and hormones. The osteoporotic
      patients had normal plasma essential amino acids but increased non-essential
      amino acids (p=0.001), particularly glutamine and glycine. The ratio
      essential/non-essential amino acids, an index of protein nutritional status, was
      decreased in the MIO patients (0.59 (0.04) MUmol/l, mean (SD)), compared to
      controls (0.66 (0.05), p=0.001). In the MIO patients, the ratio essential/non
      essential plasma amino acids (r=0.60, p=0.003) was positively correlated with
      lumbar spine bone mineral density. The erythrocyte amino acids represent a large
      proportion of the free amino acids in blood. A novel finding was the lower levels
      of erythrocyte tryptophan in MIO (12 (2) MUmol/l) compared to controls (16 (3),
      p=0.001) and decreased erythrocyte/plasma ratio (0.28 (0.07) vs. 0.33, (0.06),
      p<0.01), suggesting an altered amino acid transport of tryptophan between plasma
      and erythrocytes. In the combined group of MIO and control men (n=42), bone
      mineral density was positively correlated with erythrocyte tryptophan in both the
      lumbar spine (r=0.45, p=0.003) and femoral neck (r=0.56, p<0.001). The bone
      histomorphometric variables wall thickness, trabecular thickness and mineral
      apposition rate were all positively associated with erythrocyte tryptophan levels
      in the MIO patients. In the combined group of MIO and controls, a multiple
      regression analysis showed that erythrocyte tryptophan could explain 22% of the
      variation of lumbar spine and 30% of the variation in femoral neck bone mineral
      density. We conclude that men with idiopathic osteoporosis have changes in free
      amino acid profiles which indicate their altered utilization. The correlations
      between tryptophan and bone mineral density and bone histomorphometry suggest a
      link between tryptophan and osteoblast function which may be important for bone
      health.

PMID- 20813217
TI  - Safety of MF59-adjuvanted versus non-adjuvanted influenza vaccines in children
      and adolescents: an integrated analysis.
AB  - We reviewed the safety of MF59-adjuvanted versus non-adjuvanted influenza
      vaccines in children and adolescents (aged 6 months-18 years) in an integrated
      analysis of all pediatric trials evaluating MF59-containing influenza vaccines
      completed to date (5 trials). In the MF59-adjuvanted group (n=1181) versus the
      non-adjuvanted group (n=545) there was no increase in the incidence of
      unsolicited adverse events and serious adverse events. As expected, solicited
      local or systemic reactions occurred more frequently in MF59-adjuvanted subjects;
      however, a majority of reactions were mild and transient. These data support the
      safety of MF59-adjuvanted influenza vaccines in the pediatric population.

PMID- 20813218
TI  - ["Mental Health in the General Population: images and realities (MHGP)":
      methodology of the study].
AB  - INTRODUCTION: Mental Health is a Public Health issue, however, access to relevant
      treatment often does not meet the population needs. Patients, their relatives, as
      well as Mental Health professionals are still victims of a high stigmatization
      process. Whatever the countries and the cultural settings, public beliefs and
      attitudes towards mental illness (insanity) and mentally ills (insane people)
      play a major role in the ranking of priorities given to Mental Health national
      prevention and care policies. This paper presents the methodology of the research
      action entitled "Mental Health in General Population: images and realities
      (MHGP)" carried out by the World Health Organisation Collaborative Centre (Lille,
      France) and the Direction of research, studies, assessment and statistics (Drees)
      of the French Ministry of Health, in a sample of 36 000 French subjects over 18
      years old, between 1999 and 2003. OBJECTIVES: The MHGP Survey is an international
      multisite study aimed at: Describing, in the general population, the
      representations attached to insanity, mental illness and depression, and the
      related care; Assessing the prevalence of major psychiatric disorders in the
      general population; Rising awareness about Mental Health issues among various
      social groups: social workers, local elected, care professionals, by including
      them in the research-action procedure; Promoting the development of Community
      Psychiatry, following WHO main Guidelines. METHODS: About 900 individuals were
      recruited in 47 centres in metropolitan France between 1999 and 2003 according to
      the following criteria: i) informed consent to take part in the study, ii) age
      over 18 yrs, iii) not residing in a care institution and not homeless. Subjects
      were selected by quota sampling stratified by age, gender, educational and
      occupational level with the general population of the general population of the
      centre as sampling frame. The quotas were defined on the basis of the 1999
      national population census. The data was collected by 1700 nursing students using
      a 50-item structured questionnaire administered in face-to-face interviews; mean
      length 40 minutes. The interviewers received a special 3-day training course. The
      assessment included a specially developed questionnaire enabling description of
      representations of insane, mentally ill and depressed individuals; the Mini
      International Neuro-psychiatric Interview (Sheehan and Lecrubier); a specific
      questionnaire on care consumption in case of positive MINI diagnosis and a
      sociodemographic questionnaire. In each centre, a team of supervisors
      (psychiatric staff) coordinated the interviews and the data collection; the local
      elected and the social and care networks were given information about the
      research and the results. The results of the local study were systematically
      presented to the general population, the local elected and the social and care
      professionals. Prevalence rates of mental disorders are very similar to those
      observed in other studies. Results on social representations and public beliefs
      in general population can compare with the international data available. MHGP
      research-action remains the first study of this scale on the topic of Mental
      Health in France, combining representations and prevalences description. It
      allowed the development of anti-stigma actions at a national and local level.

PMID- 20813219
TI  - [Representations of insanity, mental illness and depression in general population
      in France].
AB  - OBJECTIVES: The aim of this study was to describe the representations of insane,
      mentally ill and depressive persons, in a representative sample from the French
      General Population. METHODS: Data were derived from the multicentric survey
      "Mental Health in the General Population: images and realities", carried out in
      47 French public sites between 1999 and 2003. A face-to-face questionnaire was
      used to interview a representative sample of French metropolitan subjects, aged
      18 and over, non-institutionalized and homeless. These subjects were recruited
      using quota sampling for age, sex, socioprofessional and education levels,
      according to data from the 1999 national French population census.
      Representations of insane, mentally ill and depressive persons were explored by a
      specific questionnaire with open and semi-open questions. Psychiatric diagnoses
      were identified using the Mini International Neuropsychiatric Interview (MINI). A
      national database was then constituted by pooling data from all sites, weighted
      for age, sex, level of education, socioprofessional level and work status to be
      representative of the French general population. RESULTS: Of the 36,000
      individuals included in this study, over 75% associated the words "insane" and
      "mentally ill" with violent and dangerous behaviours and the term "depressive"
      with sadness, isolation and suicide. Young people, those with higher education
      and higher income level more frequently associated dangerous behaviours with
      mental illness rather than with insanity. The study shows that the general
      population draws a clear line between the representation of insane and mentally
      ill on one hand, and depressive on the other hand. Insane and mentally people are
      described as abnormal, irresponsible, unconscious, socially excluded, far from
      being curable, and to be cured against their will by psychotropic drugs and
      psychiatric hospitalisation. Whereas the depressive is perceived as a more
      familiar character, suffering, curable, who can be cured with psychotropic drugs
      and social support, but not to be hospitalized. CONCLUSION: This study highlights
      the overwhelming representations of insanity and mental illness in the French
      general population. As those stereotypes strongly affect access to care and
      behaviours toward psychiatric patients, the results show the need to think over
      the best way to fight against stigma and discrimination, in order to reduce
      psychiatric patients' social exclusion.

PMID- 20813220
TI  - [Are the representations of the "madman", the "mentally ill person", the
      "depressive" and the opinions towards psychiatric hospitals homogeneous according
      to the populations of the investigated sites?].
AB  - INTRODUCTION: The concept of policy management in psychiatry requires knowledge
      representations of the "mad", the "mentally ill" and "depressed" by the people.
      It is therefore to highlight the diversity of definitions that it attributes to
      individual psychiatric disorders, particularly by cultural norms typically
      associated with geographic locations. To do this, we successively study the forms
      of stigmatisations broadly, and then by site, and the causes of thereof. But this
      does not suffice for the design of any policy in this area must also take into
      account the attitudes and behaviours of the population vis-a-vis the existing
      psychiatric facilities globally and per site. DESIGN OF STUDY: The treatments
      were carried out using data from the socio-anthropological and epidemiological
      "Mental Health in the general population: images and realities" made by the
      French Collaborating Centre of WHO for research and training Mental Health
      (WHOCC, Lille, France) and the Directorate of Research, Studies, Evaluation and
      Statistics (DREES) with 40 000 people aged 18 and older in metropolitan France
      and in the departments of overseas between 1999 and 2003. The techniques used
      range from descriptive statistics to multivariate analysis (correspondence
      analysis and multiple ascending hierarchical classification). RESULTS: The images
      of the "madness", the "mentally ill" or the "depression" in the French population
      are disparate. Nevertheless, some characteristics are found with high frequency:
      the "depressive" is rather seen as an isolated person, the "mentally ill" as a
      mental defective with bizarre speech, while "crazy" would rather characterized by
      violence (delusions and violent towards others, beat his family, incest). The
      "mentally ill" is sometimes defined by these last criteria. These images are not
      influenced by knowledge of a relative suffering from mental illness or a
      psychiatric episode experienced by the interviewee. The causes of mental illness
      (the "madness" and "mentally ill"), two contradictory trends have expressed. Some
      believe it has a physical origin, and in that case the healing is difficult and
      care must be hospitable. Others believe it was originally a non-physical
      (social), and in this case, recovery is possible, and care must be ambulatory.
      People surveyed in some sites have homogeneous opinions in this regard: Berk,
      Thuir or Gueret, the first opinion is mainly expressed, whereas the opposite
      trend was observed in Villejuif, Niort, Lille, Poitiers, Paris15, Paris10. In
      contrast, for depression, the cause is, for almost the entire population, non
      physical. Overall, 41% of French people support psychiatric hospitals, while 32%
      oppose, preferring ambulatory solutions. In fact, opinions differ so widely among
      survey sites. They are not influenced by the images of people surveyed vis-a-vis
      the "madness", the "mentally ill" or the "depression". The way of organizing
      psychiatric sectorization (taken care rather intra-hospital versus extra
      hospital, number of agents, etc.) does not influence either the image of "mad",
      the "mentally ill" or "depression" in population, nor the opinions vis-a-vis
      psychiatric hospitals. We deduce that these images are generated by other
      factors, probably cultural factors.

PMID- 20813221
TI  - [Dangerous states and mental health disorders: perceptions and reality].
AB  - Image of Madness was always strongly linked with the notion of "dangerousness",
      provoking fear and social exclusion, despite the evolution of psychiatric
      practices and organisation, and the emphasis on user's rights respect.
      Mediatization and politicization of this issue through news item combining crime
      and mental illness, reinforce and spread out this perception. This paper presents
      a review of the litterature on social perceptions associating "dangerousness",
      "Insanity" and "mental illness", available data about the link between "dangerous
      states" and "psychiatric disorders", as well as the notion of "dangerousness" and
      the assessment of "dangerous state" of people suffering or not from psychiatric
      disorders. MAPPING OF SOCIAL REPRESENTATIONS: The French Survey "Mental Health in
      General Population: Images and Realities (MHGP)" was carried out between 1999 and
      2003, on a representative sample of 36.000 individuals over 18 years old. It aims
      at describing the social representations of the population about
      "insanity/insane" and "mental illness/mentally ill". The results show that about
      75% of the people interviewed link "insanity" or "mental illness" with "criminal
      or violent acts". Young people and those with a high level of education more
      frequently categorize violent and dangerous behaviours in the field of Mental
      illness rather than in that of madness. CORRELATION BETWEEN DANGEROUS STATE AND
      PSYCHIATRIC DISORDERS: in the scientific literature, all experts reject the
      hypothesis of a direct link between violence and mental disorder. Besides, 2
      tendencies appear in their conclusions: on one hand, some studies establish a
      significative link between violence and severe mental illness, compared with the
      general population. On the other hand, results show that 87 to 97% of des
      aggressors are not mentally ills. Therefore, the absence of scientific consensus
      feeds the confusion and reinforce the link of causality between psychiatric
      disorders and violence. OFFICIAL FIGURES BY THE MINISTRY OF JUSTICE: according to
      the French Ministry of Justice, there is a lack of significative data in general
      population, that would allow the accurate evaluation of the proportion of authors
      of crimes and offences presenting a "dangerous state", either of criminological
      order or related to a psychiatric disorder. FROM "DANGEROUSNESS" TO "DANGEROUS
      STATE": the vagueness of the notion of "dangerousness" aggravates the confusion
      and reinforce the negative social representations attached to subjects labelled
      as "mentally ills". A way to alleviate this stigmatisation would be to stop using
      the word "dangerous", and rather use those of "dangerous states". Assessment of
      dangerous states is complex and needs to take into account several heterogeneous
      factors (circumstances of acting, social and family environment...). Besides, it
      is not a linear process for a given individual. Those risk factors of "dangerous
      state" lead to the construction of evaluation or prediction scales, which limits
      lay in the biaises of over or under predictive value. The overestimation of
      dangerousness is harmful, not only to individuals wrongly considered as
      "dangerous", but also to the society which, driven by safety concerns, agrees on
      the implementation of inaccurate measures. A FEW TRACKS FOR REMEDIATION: the
      representations linking "mental illness" and "dangerousness" are the major
      vectors of stigma, and deeply anchored in the collective popular imagination.
      They are shared by all population categories, with no distinction of age, gender,
      professional status or level of education. To overcome those prejudices, one has
      to carefully study their basis, their criteria, document them with statistical
      data, look for consistency and scientific rigour, in the terminology as well as
      in the methodology. Moreover, one has to encourage exchanges about this topic,
      between users, relatives, carers, local elected, politicians, media and health
      professional.

PMID- 20813222
TI  - [Mental health and social determinants].
AB  - INTRODUCTION: Social disparities in health is becoming a topic of major
      importance. Recent studies presents data on social differences in morbidity on
      various diseases. This paper shows how mental health disorders prevalences are
      strongly linked to sociological variables. It is based on the data of the
      research-action entitled "Mental Health in General Population: images and
      realities (MHGP)" carried out by the World Health Organisation Collaborative
      Centre (Lille, France) and the Direction of research, studies, assessment and
      statistics (Drees) of the French Ministry of Health, in a sample of 36 000 French
      subjects over 18 years old, between 1999 and 2003. OBJECTIVES: The MHGP Survey is
      an international multisite study aimed at assessing the prevalence of major
      psychiatric disorders in the general population, as well as describing the
      representations attached to insanity, mental illness and depression, and the
      related care. It allows the analysis of the impact of professional situation on
      prevalence data in a large sample. METHODS: The MHGP Survey was carried out in 47
      French public sites between 1999 and 2003. A face-to-face questionnaire was used
      to interview a representative sample of French metropolitan subjects, aged 18 and
      over, non-institutionalized and homeless. These subjects were recruited using
      quota sampling for age, gender, socio-professional and education levels,
      according to data from the 1999 national French population census.
      Representations of insane, mentally ill and depressive persons were explored by a
      specific questionnaire with open and semi-open questions. Psychiatric diagnoses
      were identified using the Mini International Neuropsychiatric Interview (MINI);
      including: mood disorders, anxiety disorders, alcohol and drug disorders,
      psychotic disorders and suicidal risk. A national database was then constituted
      by pooling data from all sites, weighted for age, gender, level of education,
      socio-professional level and work status to be representative of the French
      general population. Prevalence rates of mental disorders are very similar to
      those observed in other studies. Social disparities were analysed mainly using
      the work status categories, comparing employed people and unemployed people
      (unemployed, retired, students, housewife). RESULTS: Results show that mental
      disorders and suicidal risk are not fairly distributed between the various social
      categories. Half of unemployed people suffers from at least one mental disorder,
      whereas less than a third of employed people. For example, the prevalence of mood
      disorders is more than twice higher in unemployed (23.6%) than in employed
      (11.7%). Suicidal risk is specially high in unemployed people (22%) and students
      (15%). As in other pathologies and in causes of death, presence of mental
      disorder or suicidal risk negatively correlates with social status. Prevalence of
      mental disorders is higher in unemployed people and unskilled workers than in
      executives, managers and intellectual professions. Social disparities in mental
      health do not distinguish with those in health in general. Therefore, the issue
      of search for the causes of disparities is similar to that for any disparity in
      health.

PMID- 20813223
TI  - [Study of population profiles in relation to the level of suicide risk in France:
      Study "Mental health in the general population"].
AB  - Suicidal behaviour is a very important public health issue. The French study of
      mental health in the general population casts a whole new insight on this issue
      thanks to the size of the sample used, to its representative nature and to the
      variety of the collected data. This study aims at defining better the
      relationships between the factors of suicide risk within a noninstitutionalized
      adult population and more specifically between the socioeconomic and the
      psychopathological factors. The final aim is to help define the intervention
      strategies which should be developed in the context of prevention programs. The
      method used consists in estimating the suicide risk for each person included in
      the study by developing a standardized indicator. Six questions taken from the
      MINI (Mini International Neuropsychiatric Interview) were used to define the four
      levels of suicide risks which compose this indicator. Next, this indicator was
      matched for the socioeconomic variables of the study as well as for the main
      psychopathological categories. A factor analysis of the numerous relations was
      then carried out. Its principle consisted in synthesizing the information
      contained in a great number of variables and individuals thanks to the
      mathematical projection of these features onto a graph. The variables which were
      retained for the analysis were those which presented the richest relationship
      with the main variable.(that is to say the level of suicide risk). The estimated
      prevalence rate of suicidal risk in the general population (with at least one
      positive answer) is 13.7% which can be divided into 9.7% of low risk, 2.1% of
      medium risk and 1.9% of high risk. The relationship between the presence of a
      psychopathology and a medium or high risk of suicide is quite significant. What
      is more, the presence of associated pathologies (comorbidities) increases the
      risk. The highest prevalence of risk is observed in psychotic and depressive
      disorders. However, suicide risk exists in some people who do not present any
      detected psychopathology : the statistical analysis reveals an excessive medium
      and high suicide risk in relation to a low family income, unemployment,
      separation and the 18 to 24 age group. The multidimensional analysis brings to
      light several specific aspects : the principal explanation shows a relationship
      between unfavourable socio economic status and the presence of suicide risk at a
      level which is not equal to zero. The second explanatory line defines the level
      of risk according to the principal psychopathological characteristics. These two
      lines define a plane which enables to differentiate low risk groups from medium
      risk groups and high risk groups. The latter consists mainly in isolated
      pathological factors or associated factors (comorbidities). The medium and high
      risk groups are composed mainly of the combination of the two variables. To
      conclude, these results - which are necessarily flimsy since they are based on
      epidemiological and statistical analysis - do however match up with the data of
      the epidemiologic literature in an interesting way and raise the question of an
      intervention and prevention strategy that would integrate better the medical
      factors and the socio economic aspects into its program. They should be completed
      by targeted forward clinical studies as well as by more precise epidemiological
      patterns.

PMID- 20813224
TI  - [Suicide risk and suicide attempt in North Pas de Calais Region. Lessons from the
      survey Mental Health in General Population].
AB  - The Sante Mentale en Population Generale Survey (Mental Health in General
      Population Survey (MHGP)) is a multicentre international research and action
      project initiated by the World Health Organisation Collaboration Centre for
      research and training in mental health. Its aims are to assess the prevalence of
      the major mental health disorders in the general adult population and from this
      to record perceptions associated with "mental illness", "madness" and
      "depression" together with different means of assistance and specialist or lay
      care. In this work we present the analysis of data on risks of suicide and past
      history of suicide attempts in the Nord pas de Calais region. We present the
      qualitative features of these phenomena and correlations with socio-economic,
      cultural and psychopathological factors, which are discussed in terms of both
      protective and vulnerability factors. Risk of suicide is present in 15% of the
      Nord pas de Calais population and is divided into 10.44% slight risk, 2.37%
      moderate risk and 2.2% high risk. A comparison with data from the MHGP survey in
      other regions reveals the high risk of suicide in the NPDC region. A risk of
      suicide is present is 13% of the population in other SMPG survey regions, broken
      down into 9.1% low risk, 2.1% medium risk and 1.7% high risk. Compared to the
      2.2% high risk figure for NPDC, the population in this category is 21% larger. In
      terms of risk and protective factors, a bivariate analysis of socio-economic and
      cultural factors confirms the classical risk factors of sex, marital,
      occupational and educational status and income. The odds-ratio for these socio
      economic and cultural factors can be calculated from logistic regression and the
      protective factors ranked in decreasing order from religion (Muslim versus other
      religions), martial status (marked versus separated), age (over 58 years old),
      occupational status (working or retired versus unemployed), income (more than
      1300 euros versus less than 840 euros), sex (men versus women) and immigration.
      For mental illness, the bivariate analysis confirms that the risk of suicide is
      significantly higher regardless of the mental disorder in question. Logistic
      regression categorises the mental illnesses as risk factors in the following
      order: depression, psychotic disorders, anxiety, alcohol abuse disorders, other
      drugs and insomnia. Suicide attempts have been made by 9.7% of the study
      population. This figure should be compared with the 8% of the study population in
      other regions in the survey and represents 29% more attempts. For the risk and
      protective factors the results of the bivariate analysis of socio-economic on
      cultural and psychopathological factors are superimposeable on those found for
      risk of suicide. The ranking of protective factors obtained from logistic
      regression places age in first position followed in decreasing order by religion,
      martial status, income, employment status and finally sex and immigration. The
      same ranking of mental illnesses by logistic regression places depression as the
      greatest risk factor followed by anxiety, psychotic disorders, alcohol abuse
      disorders, drugs and insomnia.

PMID- 20813225
TI  - [Mental Health of elderly people: The prevalence and representations of
      psychiatric disorders].
AB  - Upon the national data basis of the huge study "Mental Health in General
      Population", elaborated by the WHO Collaborating Centre, our research tries to
      identify the particularities of the advanced years population. The increasing
      number of the elderly in France and all over the world, as well as the
      demographic evolution prospects, truly justify our interest for them. A group of
      subjects older than 65 years old - representing 21,1% of the general population -
      was divided into two parts and the 65-74 years old (12.6%) - the 75 old years old
      and more (8.5%) - and was compared to the population between 18 and 74 years old
      (78.9%) who answered this investigation. The aim of our study was to detect the
      prevalence of the main psychic troubles of the elderly (depression, anxiety,
      addiction and psychiatric disorders), with a psychiatric tool, the Mini
      International Neuropsychiatric Interview (MINI). We also wanted to perceive how
      their perceptions and representations of the behaviours and clinical symptoms of
      the psychic troubles could be different from the ones of younger people. Thus,
      and according to the answers "normal/abnormal", "dangerous/not dangerous" linked
      to each item, we measured the possible difference between the answers and the
      representations of the general population towards the elderly. The elderly are
      generally confronted to multiple psychosocial stress factors (decrease of the
      cognitive performances, decline of the sensory abilities, drop of the social
      relationships, change of status, succession of loss and breach as well as the
      cessation of the professional activity and its network, which may favour the
      emergence of troubles. According to this, a higher rate of psychic troubles among
      the elderly than in the general investigated population, may be suspected.
      However, the study in general population points out that the prevalence of
      persons suffering from at least one trouble with the MINI declines among the
      subjects belonging to the highest brackets: 34.4% for the 18-64 years old, 23.2%
      for the 65-74 years, and 22.9% for the elderly, 75 years old and more. Anxiety
      decreases with the ageing (23.4% among the less than 65 years old, instead of
      12.7% for the 75 years and more) as well as the addictive behaviours and the
      psychotic disorders (3.1% for the less than 65 years old, instead of 1.1% for the
      75 years old and more). In the register of the social representations, a few
      differences appear also between the elderly - from 65 to 74 years old and 75
      years old and more - and the majors under 65 years old: For the spectrum: T.P.S.A
      (sadness, tears, suicide, anxiety), the elderly consider these situations as
      pathological more often. The withdrawal behaviours are likely more perceived as
      "abnormal" by the elderly; The delusion, the hallucinations, the "odd" behaviours
      and talks are less often called "dangerous/non-dangerous", which leads to a
      rather different way of considering the elderly. Paramount the classical allowed
      image of the elderly - fearful, distrustful, intolerant towards any transgression
      and selfishly centred on their own the study reveals new conditions particularly
      in pointing out, among the elderly, less fear towards violent behaviours and more
      toleration towards the addicted subjects.

PMID- 20813226
TI  - Passive leg raising induced brachial artery dilation: is an old technique a
      simpler method to measure endothelial function?
AB  - OBJECTIVES: Passive leg raising (PLR) is a diagnostic maneuver that has been
      shown to cause brachial artery dilation (BAD). The objectives of this study were
      to compare BAD induced by PLR with flow mediated dilation (FMD), and to
      investigate the mechanism of PLR-BAD. We studied a total of 75 subjects with and
      without cardiovascular risk factors/disease in order to provide a wide range of
      FMD responses. METHODS: Using ultrasound, PLR-BAD and FMD induced by release of
      arterial cuff occlusion were measured. RESULTS: BA diameter increased from
      0.33+0.06 at baseline to 0.35+/-0.06 cm (p<.001) (4.8% increase) upon PLR and
      from 0.33+/-0.06 to 0.37+/-0.06 (11.8%) upon hyperemia. PLR induced BAD was
      significantly correlated with FMD (r=.82, p<.001). On receiver operating
      characteristic analysis of the two techniques, the area under the curve was 0.86
      (95% CI 0.79-0.94, p<.001). Heart rate variability measures remained unchanged
      upon PLR indicating minimal contributions from changes in autonomic activity. The
      combination of FMD and PLR did not result in greater BAD than did FMD alone
      consistent with a common underlying mechanism. Mean blood flow velocity increased
      prior to BAD suggesting that shear stress increases prior to BAD. CONCLUSIONS:
      BAD occurs in response to PLR and is proportional to FMD, although the magnitude
      of PLR-BAD is less than half that of FMD. It appears to occur by the same
      endothelial dependent mechanism as FMD. PLR-BAD may be used as a surrogate
      measure of FMD to evaluate vascular function, and has the advantage of being
      simpler to perform.

PMID- 20813227
TI  - Surgical and prosthodontic reconstruction of a gunshot injury of the mandible
      using dental implants and an acrylic resin fixed prosthesis: a clinical report.
AB  - Gunshot injuries to the face can have serious esthetic and functional
      consequences. Few articles have described the comprehensive management, including
      surgical and prosthodontic phases of reconstruction, of patients with such
      injuries. This clinical report describes a 3-year follow-up of the maxillofacial
      rehabilitation of a gunshot injury to the left mandible using an iliac crest bone
      graft, dental implants, and an economical acrylic resin fixed prosthesis. The
      importance of a multidisciplinary approach and biomechanical considerations for
      implant positioning in posterior mandibular reconstructions are described.
      Various prosthetic designs and the choice of available prosthetic materials are
      also discussed.

PMID- 20813228
TI  - In vitro fatigue resistance of CAD/CAM composite resin and ceramic posterior
      occlusal veneers.
AB  - STATEMENT OF PROBLEM: Thin, bonded, posterior occlusal veneers constitute a
      conservative alternative to traditional complete coverage crowns. Information
      regarding selection of the appropriate material and its influence on fatigue
      resistance, which may affect the longevity of the restoration, is missing.
      PURPOSE: The purpose of this study was to assess and compare the fatigue
      resistance of composite resin and ceramic posterior occlusal veneers. MATERIAL
      AND METHODS: Thirty extracted molars received a standardized nonretentive tooth
      preparation (simulating advanced occlusal erosion), including removal of occlusal
      enamel, exposure of dentin, and immediate dentin sealing (Optibond FL). All teeth
      were restored with a 1.2-mm-thick occlusal veneer (Cerec 3 chairside CAD/CAM
      system). The restorations (n=10) were milled from leucite-reinforced and lithium
      disilicate ceramics (IPS Empress CAD and IPS e.max CAD, respectively) and a
      composite resin (Paradigm MZ100). The intaglio surfaces of the ceramic
      restorations were conditioned by hydrofluoric acid etching and silane. Airborne
      particle abrasion and silane were used to condition the composite resin
      restorations. Preparations were airborne-particle abraded and etched. All
      restorations were bonded with preheated luting material and submitted to cyclic
      isometric loading at 5 Hz, starting with a load of 200 N (x5000 cycles), followed
      by stepwise loading of 400, 600, 800, 1000, 1200, and 1400 N at a maximum of
      30,000 cycles each. The number of cycles at initial failure (first cracks) was
      recorded. Specimens were loaded for a maximum of 185,000 cycles. Groups were
      compared using the life table survival analysis (alpha=.016, Bonferroni method).
      RESULTS: IPS Empress CAD failed at an average load of 900 N, with no specimen
      withstanding all 185,000 load cycles (survival 0%), while IPS e.max CAD and
      Paradigm MZ100 demonstrated survival rates of 30% and 100%, respectively. None of
      the specimens exhibited catastrophic failure, but only cracks limited to the
      restorative material. CONCLUSIONS: Posterior occlusal veneers made of composite
      resin (Paradigm MZ100) had significantly higher fatigue resistance (P<.002)
      compared to IPS Empress CAD and IPS e.max CAD.

PMID- 20813229
TI  - Authorship characteristics in prosthodontic literature: proliferation and
      internationalization. A review and analysis following a 10-year observation.
AB  - STATEMENT OF PROBLEM: Author characteristics and the extent of dental literature
      authorship globalization have not been widely investigated, especially in
      prosthodontics. PURPOSE: The purpose of this study was to examine trends in
      authorship characteristics in prosthodontics. MATERIAL AND METHODS: Articles
      published in The Journal of Prosthetic Dentistry (JPD), International Journal of
      Prosthodontics (IJP), and Journal of Prosthodontics (JP) in 1998, 2003, and 2008
      were reviewed. Abstracts, letters to the editor, and book reviews were not
      included in the investigation. The authors' educational degrees had to be listed
      in the publications for the articles to be included. For each article, number of
      authors, degrees of all authors, academic ranks of first and last authors, and
      geographic origin were recorded. Descriptive and analytic analyses (alpha=.05),
      including a generalized linear model, Kruskal-Wallis, Mann-Whitney U, or chi
      square tests, were used as appropriate. RESULTS: A total of 998 articles met the
      inclusion criteria from the 3 selected journals for the years studied. Across all
      3 journals, the mean number of authors per article increased significantly from
      2.9 in 1998 to 3.6 in 2008 (Kruskal-Wallis, P<.001). The mean number of authors
      per article increased steadily on all continents, except for Africa and Oceania.
      A steady increase of authors with higher degrees was observed. There was a
      significant increase in the proportion of senior-ranking faculty as last author
      over time (chi-square=5.57, df=1, P=.018). The contributions from Asia and South
      America increased over time. CONCLUSIONS: The number of authors per article, the
      number of authors with higher educational degrees, and the percentage of senior
      ranking faculty as last author steadily increased in the prosthodontic literature
      from 1998 to 2008. The trend of globalization of authorship was evident in the
      prosthodontic literature.

PMID- 20813230
TI  - The effect of metal recasting on porcelain-metal bonding: a force-to-failure
      study.
AB  - STATEMENT OF PROBLEM: Noble dental alloys are commonly remelted in the dental
      laboratory, but the effect of repeated casting on porcelain bond strength
      requires further documentation. PURPOSE: The purpose of this study was to
      determine if casting up to 3 times affected metal ceramic bond strength for 3
      noble alloys using methodology in ANSI/ADA Specification No. 38. MATERIAL AND
      METHODS: Representative high-gold (Brite Gold XH), gold-palladium (W-5), and
      palladium-silver (IPS d.SIGN 53) alloys were cast into metal strips (25 x 3 x 0.5
      mm), using torch melting. IPS InLine porcelain with overall dimensions of 8 x 3 x
      1.1 mm was centrally applied on each strip. Metal ceramic specimens were also
      prepared after each alloy was melted a second and third time. There were 12
      specimens in each of the 9 groups. Force to failure and porcelain bond
      compatibility index (tau(b)) were determined for each specimen, and statistical
      comparisons were made using the Ryan-Einot-Gabriel-Welsch multiple range test
      (experimental alpha=.05). Fractured specimens were examined with a scanning
      electron microscope. RESULTS: Mean values of tau(b) for specimen groups ranged
      from 40.6 to 48.2 MPa, and there were no significant differences among the 3
      alloys after the first casting. For the high-gold alloy, tau(b) was significantly
      different for the first and third castings. Increases in size and frequency of
      interfacial voids were observed with the SEM when all alloys were cast 2
      additional times. CONCLUSIONS: All 3 alloys had adequate porcelain bond strength
      (>25 MPa). The bond strength for the high-gold alloy was significantly greater
      for the third casting than for the first casting.

PMID- 20813231
TI  - Lightness, chroma, and hue distributions of a shade guide as measured by a
      spectroradiometer.
AB  - STATEMENT OF PROBLEM: The color attributes of commercially available shade guides
      have been measured by spectrophotometers (SP), which are designed to measure flat
      surfaces. However, there is limited information on the color distribution of
      shade guides as measured by spectroradiometers (SR), which are capable of
      measuring the color of curved surfaces. PURPOSE: The purpose of this study was to
      determine the distributions of lightness (CIE L*) and chroma (C*(ab)) step
      intervals between adjacent shade tabs of a shade guide based on the lightness,
      chroma, and hue attributes measured by an SR. MATERIAL AND METHODS: Lightness,
      chroma, hue angle, and CIE a* and b* values of the shade tabs (n=26) from a shade
      guide (Vitapan 3D-Master) were measured by an SR under daylight conditions. The
      distributions of the ratios in lightness and chroma of each tab compared with the
      lowest lightness tab or the lowest chroma tab were determined. The values for
      each color parameter were analyzed by a 3-way ANOVA with the factors of
      lightness, chroma, and hue designations of the shade tabs (alpha=.05). RESULTS:
      The chroma and CIE a* and b* values were influenced by the lightness, chroma, and
      hue designations of the shade tabs (P<.001); however, the lightness and hue angle
      were influenced by the lightness and hue designations, but not by the chroma
      designation. Distributions for the CIE a* and b* values, in each lightness group,
      corresponded with the chroma designation. However, the intervals in the lightness
      and chroma scales between adjacent tabs were not uniform. CONCLUSIONS: The
      intervals in the color parameters between adjacent shade tabs were not uniform
      based on SR measurements. Therefore, a shade guide in which shade tabs are more
      equally spaced by the color attributes, based on the values as measured by an SR
      along with observers' responses with respect to the equality of the intervals,
      should be devised.

PMID- 20813232
TI  - A comparison of the rigidity of five mandibular major connectors for partial
      removable dental prostheses via load deflection.
AB  - STATEMENT OF PROBLEM: The rigidity of the major connector for partial removable
      dental prostheses (PRDP) has not been well defined. There is little scientific
      evidence to support specific standards relative to the dimensions of a casting
      and their effect on long-term function of the PRDP or the supporting tissues.
      PURPOSE: The purpose of this study was to compare in vitro the effects of load
      deflection of 5 clinically used mandibular major connector forms. MATERIAL AND
      METHODS: A partially edentulous dental cast of a patient with the mandibular
      anterior teeth remaining was used as the test model. Lingual plate (LP),
      continuous bar (CB), sublingual bar (SB), lingual bar (LB), and dental lingual
      bar (DLB) specimens (n=5) were waxed on identical refractory casts, then cast in
      cobalt base alloy and finished. Each specimen was placed on a custom test table
      and statically loaded in the contralateral second molar region with 500 g in the
      horizontal and vertical planes. Deflections were measured at the terminal
      abutment rest seat, anterior to the load. Comparisons between group means were
      evaluated using the Dunnett T3 method, assuming unequal variances, for all
      pairwise tests at a .05 significance level and for 95% confidence intervals for
      group mean differences. Differences within the groups for vertical versus
      horizontal deflections were compared using a paired t test and Bonferroni
      correction (alpha=.05 for all tests). RESULTS: Horizontal deflection between LP
      and LB, CB and LB, and SB and LB were significant, with the first in each
      comparison having the least amount of deflection. A significant difference was
      also seen in the vertical deflection, with the first in each comparison observed
      to have deflected the least for LP versus CB, LP versus LB, LP versus DLB, CB
      versus DLB, LB versus DLB, and SB versus DLB. The amount of vertical deflection
      was significantly greater than the horizontal deflection for all 5 mandibular
      major connectors (P< or =.033). CONCLUSIONS: In the horizontal plane, a
      significant difference in the amount of deflection was seen between the LP and
      LB, CB and LB, and LB and SB. In the vertical plane, the LP deflected
      significantly less than the CB, LB, and DLB. In addition, the DLB deflected
      significantly more in the vertical plane when compared to the CB, LB, and SB. All
      5 mandibular major connectors had a significantly greater amount of vertical
      deflection as compared to horizontal deflection.

PMID- 20813233
TI  - A comparison of simulated jaw dynamics in models of segmental mandibular
      resection versus resection with alloplastic reconstruction.
AB  - STATEMENT OF PROBLEM: Composite mandibular resection resulting in mandibular
      discontinuity can alter jaw motion, occlusal forces, and mastication, whether or
      not the jaw is reconstructed. The biomechanical events associated with these
      changes are difficult to assess clinically and, therefore, are not well
      documented or researched. PURPOSE: The purpose of this study was to model
      movements of a mandible with a discontinuity defect, and to compare them to
      movements of a mandible with its continuity restored by alloplastic
      reconstruction. MATERIAL AND METHODS: Computational models were created with a
      novel simulation platform. The variables designed into the models included
      gravity, external forces, and jaw muscle activity. Each jaw was observed at rest,
      when opened by external force or by muscle drive, and during the generation of
      unilateral occlusal force on the nonoperated side. Scarring was simulated with
      springlike forces. Outputs included individual muscle forces and torques, as well
      as mandibular incisor and condylar motions. RESULTS: Both models displayed
      plausible resting postures, and jaw opening with deviation toward the defect side
      when scarring was simulated. Opening caused by downward force on the incisors
      differed from that due to muscle activation. Jaw rotations during unilateral
      molar contact on the unaffected side were muscle specific and influenced by
      mandibular discontinuity. CONCLUSIONS: Plausible jaw movements after
      hemimandibulectomy and/or alloplastic reconstruction could be predicted by
      dynamic modeling. The effect of soft tissue forces on jaw posture and movements
      varied with the condylar support available. In both models, different opening
      trajectories were produced by external force on the jaw and by jaw muscle
      activation. Mandibular rotation during unilateral molar contact depended on which
      muscles were activated, and the availability of bilateral condylar support.

PMID- 20813234
TI  - A technique for indirect fabrication of a complete-arch, implant-supported, fixed
      provisional restoration from a radiographic template.
AB  - This article describes an alternative technique for the fabrication of a complete
      arch, implant-supported, cement-retained, fixed provisional restoration. The
      definitive cast is fabricated from the surgical guide and the provisional
      restoration is fabricated indirectly from the radiographic guide. This technique
      is an easy and time-saving procedure to fabricate an interim prosthesis for
      immediate or delayed loading of implants.

PMID- 20813235
TI  - Creating esthetic posterior restorations by developing anatomical grooves and
      fossae.

PMID- 20813236
TI  - Sterilization of vinyl polysiloxane impression material.

PMID- 20813237
TI  - International Review of Neurobiology. Functional plasticity and genetic
      variation: insights into the neurobiology of alcoholism. Preface.

PMID- 20813238
TI  - The role of microRNAs in drug addiction: a big lesson from tiny molecules.
AB  - Alcoholism is a multifactorial disease of unclear molecular underpinnings.
      Currently, we are witnessing a major shift in our understanding of the functional
      elements of the genome, which could help us to discover novel insights into the
      nature of alcoholism. In humans, the vast majority of the genome encodes non
      protein-coding DNA with unclear function. Recent research has started to unveil
      this mystery by describing the functional relevance of microRNAs, and examining
      which genes are regulated by non-protein-coding DNA. Here, I describe alcohol
      regulation of microRNAs and provide examples of microRNAs that control the
      expression of alcohol-relevant genes. Emphasis is put on the potential of
      microRNAs in explaining the polygenic nature of alcoholism and prospects of
      microRNA research and future directions of this burgeoning field.

PMID- 20813239
TI  - The genetics of behavioral alcohol responses in Drosophila.
AB  - Drosophila melanogaster is commonly found near rotting or fermenting fruit,
      reflected in its name pomace, or vinegar fly. In such environments, flies often
      encounter significant levels of ethanol. Three observations have made Drosophila
      a very promising model organism to understand the genetic contributions to the
      behavioral responses to alcohol. First, similar to higher vertebrates, flies show
      hyperactivation upon exposure to a low to medium dose of alcohol, while high
      doses can lead to sedation. In addition, when given a choice, flies will actually
      prefer alcohol-containing food over regular food. Second, the genes and
      biochemical pathways implicated in controlling these behavioral responses in
      flies are also participating in determining alcohol responses, and drinking
      behavior in mammals. Third, the fact that flies have been studied genetically for
      over one hundred years means that an exceptional repertoire of genetic tools are
      at our disposal. Here, we will review some of these tools and experimental
      approaches, survey the methods for, and measures after Drosophila ethanol
      exposure, and discuss the different molecular components and functional pathways
      involved in these behavioral responses to alcohol.

PMID- 20813242
TI  - Genetic variation and brain gene expression in rodent models of alcoholism
      implications for medication development.
AB  - Much research on experimental animals that is aimed to decipher genetic factors
      involved in alcoholism has been devoted to either models of innate alcohol
      related phenotypes or responses after acute alcohol challenge. Such focus has,
      however, limitations when it comes to the pathogenetic mechanism underlying
      alcohol addiction, because the progression into the disorder takes years and
      genetic as well as environmental factors may exert different influences along
      this trajectory. Animal models of the neuroadaptations involved in the
      development of dependence exist, but have been difficult to implement for genetic
      and genomics analysis. Consequently, currently available data have been difficult
      to reconcile with the human condition and could be misleading in predicting
      targets for medication development. This review will illustrate strengths and
      pitfalls of genomic approaches in rodent models of alcoholism and emphasize the
      need for convergent lines of evidence to improve the predictive value of such
      studies. Examples of a convergent research approach include validation studies
      for Agt, Arrb2, Crhr1, Grin3a, and Npy.

PMID- 20813240
TI  - Neural plasticity, human genetics, and risk for alcohol dependence.
AB  - Opportunities for advances in the neurobiology of alcohol dependence have been
      facilitated by the development of sophisticated neurophysiological and
      neuroimaging techniques that allow us to have a window on developmental changes
      in brain structure and function. The search for genes that may increase
      susceptibility to alcohol dependence has been greatly facilitated by the
      recognition that intermediate phenotypes, sometimes referred to as
      endophenotypes, may be closer to the genetic variation than is the more complex
      alcohol dependence phenotype. This chapter will review the evidence that the
      brain is highly plastic, exhibiting major postnatal changes, especially during
      adolescence, in neural circuits that appear to influence addiction
      susceptibility. This chapter will suggest that heritable aspects of brain
      structure and function that are seen developmentally may be an important
      endophenotypic characteristic associated with familial risk for developing
      alcohol dependence. Finally, a review of studies showing associations between
      brain structural and functional characteristics and specific genes will be
      offered.

PMID- 20813241
TI  - Using expression genetics to study the neurobiology of ethanol and alcoholism.
AB  - Recent simultaneous progress in human and animal model genetics and the advent of
      microarray whole genome expression profiling have produced prodigious data sets
      on genetic loci, potential candidate genes, and differential gene expression
      related to alcoholism and ethanol behaviors. Validated target genes or gene
      networks functioning in alcoholism are still of meager proportions. Genetical
      genomics, which combines genetic analysis of both traditional phenotypes and
      whole genome expression data, offers a potential methodology for characterizing
      brain gene networks functioning in alcoholism. This chapter will describe
      concepts, approaches, and recent findings in the field of genetical genomics as
      it applies to alcohol research.

PMID- 20813243
TI  - Identifying quantitative trait loci (QTLs) and genes (QTGs) for alcohol-related
      phenotypes in mice.
AB  - Alcoholism is a complex clinical disorder with genetic and environmental
      contributions. Although no animal model duplicates alcoholism, models for
      specific factors, such as the withdrawal syndrome, are useful to identify
      potential genetic determinants of liability in humans. Murine models have been
      invaluable to identify quantitative trait loci (QTLs) that influence a variety of
      alcohol responses. However, the QTL regions are typically large, at least
      initially, and contain numerous genes, making identification of the causal
      quantitative trait gene(s) (QTGs) challenging. Here, we present QTG
      identification strategies currently used in the field of alcohol genetics and
      discuss relevance to alcoholic human populations.

PMID- 20813244
TI  - Glutamate plasticity in the drunken amygdala: the making of an anxious synapse.
AB  - Plasticity at glutamatergic synapses is believed to be the cellular correlate of
      learning and memory. Classic fear conditioning, for example, is dependent upon
      NMDA-type glutamate receptor activation in the lateral/basolateral amygdala
      followed by increased synaptic expression of AMPA-type glutamate receptors. This
      review provides an extensive comparison between the initiation and expression of
      glutamatergic plasticity during learning/memory and glutamatergic alterations
      associated with chronic ethanol exposure and withdrawal. The parallels between
      these neuro-adaptive processes suggest that long-term ethanol exposure might
      "chemically condition" amygdala-dependent fear/anxiety via the increased function
      of pre- and post-synaptic glutamate signaling.

PMID- 20813247
TI  - BK channel and alcohol, a complicated affair.
AB  - Alcohol is a fast acting molecule that alters behavior within a few minutes of
      absorption. Its rapid behavioral impact suggests early action on ion channels. Of
      all voltage-gated potassium ion channels, BK channels, a subcategory of potassium
      channels characterized by their large unitary conductance, and by their capacity
      of being activated synergistically by membrane potential and intracellular free
      calcium, are unique due to their high sensitivity to alcohol. In this review, we
      discuss BK channels structure and function, and how they help us understand the
      various ways BK channel mediates alcohol's effects on neuronal function and on
      behavior in the striatum.

PMID- 20813246
TI  - Alcohol and the prefrontal cortex.
AB  - The prefrontal cortex occupies the anterior portion of the frontal lobes and is
      thought to be one of the most complex anatomical and functional structures of the
      mammalian brain. Its major role is to integrate and interpret inputs from
      cortical and sub-cortical structures and use this information to develop
      purposeful responses that reflect both present and future circumstances. This
      includes both action-oriented sequences involved in obtaining rewards and
      inhibition of behaviors that pose undue risk or harm to the individual. Given the
      central role in initiating and regulating these often complex cognitive and
      behavioral responses, it is no surprise that alcohol has profound effects on the
      function of the prefrontal cortex. In this chapter, we review the basic anatomy
      and physiology of the prefrontal cortex and discuss what is known about the
      actions of alcohol on the function of this brain region. This includes a review
      of both the human and animal literature including information on the
      electrophysiological and behavioral effects that follow acute and chronic
      exposure to alcohol. The chapter concludes with a discussion of unanswered
      questions and areas needing further investigation.

PMID- 20813248
TI  - A review of synaptic plasticity at Purkinje neurons with a focus on ethanol
      induced cerebellar dysfunction.
AB  - The cerebellum controls balance, posture, motor coordination, and cognition, and
      studies suggest that ethanol impairs these cerebellar functions. However, the
      mechanisms through which ethanol produces these effects are not fully understood.
      Here, we review evidence suggesting that ethanol acts, in part, by impairing
      synaptic plasticity mechanisms at cerebellar Purkinje neurons. We will primarily
      focus on recent experiments indicating that long-term depression at both parallel
      fiber- and climbing fiber-Purkinje cell synapses is inhibited by acute ethanol
      exposure. We will also discuss experimental evidence showing that chronic
      prenatal ethanol exposure converts long-term depression into long-term
      potentiation at parallel fiber-Purkinje cell synapses.

PMID- 20813250
TI  - Phosphotyrosine signaling: evolving a new cellular communication system.
AB  - Tyrosine phosphorylation controls many cellular functions. Yet the three-part
      toolkit that regulates phosphotyrosine signaling-tyrosine kinases,
      phosphotyrosine phosphatases, and Src Homology 2 (SH2) domains-is a relatively
      new innovation. Genomic analyses reveal how this revolutionary signaling system
      may have originated and why it rapidly became critical to metazoans.

PMID- 20813251
TI  - What controls T cell receptor phosphorylation?

PMID- 20813245
TI  - Ethanol action on dopaminergic neurons in the ventral tegmental area: interaction
      with intrinsic ion channels and neurotransmitter inputs.
AB  - The dopaminergic system originating in the midbrain ventral tegmental area (VTA)
      has been extensively studied over the past decades as a critical neural substrate
      involved in the development of alcoholism and addiction to other drugs of abuse.
      Accumulating evidence indicates that ethanol modulates the functional output of
      this system by directly affecting the firing activity of VTA dopamine neurons,
      whereas withdrawal from chronic ethanol exposure leads to a reduction in the
      functional output of these neurons. This chapter will provide an update on the
      mechanistic investigations of the acute ethanol action on dopamine neuron
      activity and the neuroadaptations/plasticities in the VTA produced by previous
      ethanol experience.

PMID- 20813252
TI  - Response multilayered control of T cell receptor phosphorylation.

PMID- 20813253
TI  - Fishing out a sensor for anti-inflammatory oils.
AB  - The omega-3 fatty acids have anti-inflammatory and antidiabetic effects in
      humans. Now, Oh et al. (2010) demonstrate that the G protein-coupled receptor
      GPR120 is a receptor for omega-3 fatty acids on macrophages and fat cells.
      Activation of GPR120 by omega-3 fatty acids inhibits multiple inflammation
      cascades in macrophages and reverses insulin resistance in obese mice.

PMID- 20813254
TI  - A new spin on planar cell polarity.
AB  - The generation of planar cell polarity (PCP) and tissue shape during
      morphogenesis is tightly linked, but it is not clear how. Aigouy et al. (2010)
      now show in the developing Drosophila wing that PCP initially has a radial
      orientation that becomes realigned to the proximal-distal axis of organ shape by
      mechanical forces and cell rearrangements mediated by Dachsous.

PMID- 20813255
TI  - Viable rat-mouse chimeras: where do we go from here?
AB  - In a tour-de-force study, Kobayashi et al. (2010) describe the first viable rat
      mouse chimeras and demonstrate that rat induced pluripotent stem (iPS) cells can
      rescue organ deficiency in mice. Rat iPS cells formed a fully functional pancreas
      when injected into mouse blastocysts lacking the Pdx1 gene required for pancreas
      formation.

PMID- 20813256
TI  - 'Fore brain: a hint of the ancestral cortex.
AB  - By combining gene expression profiling with image registration, Tomer et al.
      (2010) find that the mushroom body of the segmented worm Platynereis dumerilii
      shares many features with the mammalian cerebral cortex. The authors propose that
      the mushroom body and cortex evolved from the same structure in the common
      ancestor of vertebrates and invertebrates.

PMID- 20813257
TI  - The language of histone crosstalk.
AB  - It has been suggested that a specific pattern of histone posttranslational
      modifications and their crosstalk may constitute a code that determines
      transcriptional outcomes. However, recent studies indicate that histone
      modifications have context-dependent effects, making their interplay more like a
      language within the chromatin signaling pathway than a code.

PMID- 20813258
TI  - GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and
      insulin-sensitizing effects.
AB  - Omega-3 fatty acids (omega-3 FAs), DHA and EPA, exert anti-inflammatory effects,
      but the mechanisms are poorly understood. Here, we show that the G protein
      coupled receptor 120 (GPR120) functions as an omega-3 FA receptor/sensor.
      Stimulation of GPR120 with omega-3 FAs or a chemical agonist causes broad anti
      inflammatory effects in monocytic RAW 264.7 cells and in primary intraperitoneal
      macrophages. All of these effects are abrogated by GPR120 knockdown. Since
      chronic macrophage-mediated tissue inflammation is a key mechanism for insulin
      resistance in obesity, we fed obese WT and GPR120 knockout mice a high-fat diet
      with or without omega-3 FA supplementation. The omega-3 FA treatment inhibited
      inflammation and enhanced systemic insulin sensitivity in WT mice, but was
      without effect in GPR120 knockout mice. In conclusion, GPR120 is a functional
      omega-3 FA receptor/sensor and mediates potent insulin sensitizing and
      antidiabetic effects in vivo by repressing macrophage-induced tissue
      inflammation.

PMID- 20813260
TI  - The ATAC acetyltransferase complex coordinates MAP kinases to regulate JNK target
      genes.
AB  - In response to extracellular cues, signal transduction activates downstream
      transcription factors like c-Jun to induce expression of target genes. We
      demonstrate that the ATAC (Ada two A containing) histone acetyltransferase (HAT)
      complex serves as a transcriptional cofactor for c-Jun at the Jun N-terminal
      kinase (JNK) target genes Jra and chickadee. ATAC subunits are required for c-Jun
      occupancy of these genes and for H4K16 acetylation at the Jra enhancer, promoter,
      and transcribed sequences. Under conditions of osmotic stress, ATAC colocalizes
      with c-Jun, recruits the upstream kinases Misshapen, MKK4, and JNK, and
      suppresses further activation of JNK. Relocalization of these MAPKs and
      suppression of JNK activation by ATAC are dependent on the CG10238 subunit of
      ATAC. Thus, ATAC governs the transcriptional response to MAP kinase signaling by
      serving as both a coactivator of transcription and as a suppressor of upstream
      signaling.

PMID- 20813259
TI  - Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and
      eradicate non-Hodgkin lymphoma.
AB  - Monoclonal antibodies are standard therapeutics for several cancers including the
      anti-CD20 antibody rituximab for B cell non-Hodgkin lymphoma (NHL). Rituximab and
      other antibodies are not curative and must be combined with cytotoxic
      chemotherapy for clinical benefit. Here we report the eradication of human NHL
      solely with a monoclonal antibody therapy combining rituximab with a blocking
      anti-CD47 antibody. We identified increased expression of CD47 on human NHL cells
      and determined that higher CD47 expression independently predicted adverse
      clinical outcomes in multiple NHL subtypes. Blocking anti-CD47 antibodies
      preferentially enabled phagocytosis of NHL cells and synergized with rituximab.
      Treatment of human NHL-engrafted mice with anti-CD47 antibody reduced lymphoma
      burden and improved survival, while combination treatment with rituximab led to
      elimination of lymphoma and cure. These antibodies synergized through a mechanism
      combining Fc receptor (FcR)-dependent and FcR-independent stimulation of
      phagocytosis that might be applicable to many other cancers.

PMID- 20813262
TI  - Photoadaptation in Neurospora by competitive interaction of activating and
      inhibitory LOV domains.
AB  - Light responses and photoadaptation of Neurospora depend on the photosensory
      light-oxygen-voltage (LOV) domains of the circadian transcription factor White
      Collar Complex (WCC) and its negative regulator VIVID (VVD). We found that light
      triggers LOV-mediated dimerization of the WCC. The activated WCC induces
      expression of VVD, which then disrupts and inactivates the WCC homodimers by the
      competitive formation of WCC-VVD heterodimers, leading to photoadaptation. During
      the day, expression levels of VVD correlate with light intensity, allowing
      photoadaptation over several orders of magnitude. At night, previously
      synthesized VVD serves as a molecular memory of the brightness of the preceding
      day and suppresses responses to light cues of lower intensity. We show that VVD
      is essential to discriminate between day and night, even in naturally ambiguous
      photoperiods with moonlight.

PMID- 20813261
TI  - A bacterial mRNA leader that employs different mechanisms to sense disparate
      intracellular signals.
AB  - Bacterial mRNAs often contain leader sequences that respond to specific
      metabolites or ions by altering expression of the associated downstream protein
      coding sequences. Here we report that the leader RNA of the Mg(2+) transporter
      gene mgtA of Salmonella enterica, which was previously known to function as a
      Mg(2+)-sensing riboswitch, harbors an 18 codon proline-rich open reading frame
      termed mgtL-that permits intracellular proline to regulate mgtA expression.
      Interfering with mgtL translation by genetic, pharmacological, or environmental
      means was observed to increase the mRNA levels from the mgtA coding region.
      Substitution of the mgtL proline codons by other codons abolished the response to
      proline and to hyperosmotic stress but not to Mg(2+). Our findings show that mRNA
      leader sequences can consist of complex regulatory elements that utilize
      different mechanisms to sense separate signals and mediate an appropriate
      cellular response.

PMID- 20813263
TI  - Cell flow reorients the axis of planar polarity in the wing epithelium of
      Drosophila.
AB  - Planar cell polarity (PCP) proteins form polarized cortical domains that govern
      polarity of external structures such as hairs and cilia in both vertebrate and
      invertebrate epithelia. The mechanisms that globally orient planar polarity are
      not understood, and are investigated here in the Drosophila wing using a
      combination of experiment and theory. Planar polarity arises during growth and
      PCP domains are initially oriented toward the well-characterized organizer
      regions that control growth and patterning. At pupal stages, the wing hinge
      contracts, subjecting wing-blade epithelial cells to anisotropic tension in the
      proximal-distal axis. This results in precise patterns of oriented cell
      elongation, cell rearrangement and cell division that elongate the blade proximo
      distally and realign planar polarity with the proximal-distal axis. Mutation of
      the atypical Cadherin Dachsous perturbs the global polarity pattern by altering
      epithelial dynamics. This mechanism utilizes the cellular movements that sculpt
      tissues to align planar polarity with tissue shape.

PMID- 20813264
TI  - Generation of rat pancreas in mouse by interspecific blastocyst injection of
      pluripotent stem cells.
AB  - The complexity of organogenesis hinders in vitro generation of organs derived
      from a patient's pluripotent stem cells (PSCs), an ultimate goal of regenerative
      medicine. Mouse wild-type PSCs injected into Pdx1(-/-) (pancreatogenesis
      disabled) mouse blastocysts developmentally compensated vacancy of the pancreatic
      "developmental niche," generating almost entirely PSC-derived pancreas. To
      examine the potential for xenogenic approaches in blastocyst complementation, we
      injected mouse or rat PSCs into rat or mouse blastocysts, respectively,
      generating interspecific chimeras and thus confirming that PSCs can contribute to
      xenogenic development between mouse and rat. The development of these mouse/rat
      chimeras was primarily influenced by host blastocyst and/or foster mother,
      evident by body size and species-specific organogenesis. We further injected rat
      wild-type PSCs into Pdx1(-/-) mouse blastocysts, generating normally functioning
      rat pancreas in Pdx1(-/-) mice. These data constitute proof of principle for
      interspecific blastocyst complementation and for generation in vivo of organs
      derived from donor PSCs using a xenogenic environment.

PMID- 20813265
TI  - Profiling by image registration reveals common origin of annelid mushroom bodies
      and vertebrate pallium.
AB  - The evolution of the highest-order human brain center, the "pallium" or "cortex,"
      remains enigmatic. To elucidate its origins, we set out to identify related brain
      parts in phylogenetically distant animals, to then unravel common aspects in
      cellular composition and molecular architecture. Here, we compare vertebrate
      pallium development to that of the mushroom bodies, sensory-associative brain
      centers, in an annelid. Using a newly developed protocol for cellular profiling
      by image registration (PrImR), we obtain a high-resolution gene expression map
      for the developing annelid brain. Comparison to the vertebrate pallium reveals
      that the annelid mushroom bodies develop from similar molecular coordinates
      within a conserved overall molecular brain topology and that their development
      involves conserved patterning mechanisms and produces conserved neuron types that
      existed already in the protostome-deuterostome ancestors. These data indicate
      deep homology of pallium and mushroom bodies and date back the origin of higher
      brain centers to prebilaterian times.

PMID- 20813267
TI  - SnapShot: Nuclear receptors I.

PMID- 20813268
TI  - Preface: Healthcare associated infections in the neonatal intensive care unit.

PMID- 20813266
TI  - The protein composition of mitotic chromosomes determined using multiclassifier
      combinatorial proteomics.
AB  - Despite many decades of study, mitotic chromosome structure and composition
      remain poorly characterized. Here, we have integrated quantitative proteomics
      with bioinformatic analysis to generate a series of independent classifiers that
      describe the approximately 4,000 proteins identified in isolated mitotic
      chromosomes. Integrating these classifiers by machine learning uncovers
      functional relationships between protein complexes in the context of intact
      chromosomes and reveals which of the approximately 560 uncharacterized proteins
      identified here merits further study. Indeed, of 34 GFP-tagged predicted
      chromosomal proteins, 30 were chromosomal, including 13 with centromere
      association. Of 16 GFP-tagged predicted nonchromosomal proteins, 14 were
      confirmed to be nonchromosomal. An unbiased analysis of the whole chromosome
      proteome from genetic knockouts of kinetochore protein Ska3/Rama1 revealed that
      the APC/C and RanBP2/RanGAP1 complexes depend on the Ska complex for stable
      association with chromosomes. Our integrated analysis predicts that up to 97 new
      centromere-associated proteins remain to be discovered in our data set.

PMID- 20813269
TI  - Staphylococcus aureus: a continuously evolving and formidable pathogen in the
      neonatal intensive care unit.
AB  - Staphylococcus aureus is a continuously evolving and formidable pathogen that has
      been a problem for both healthy and sick neonates for decades. Much focus over
      the past 20 years has been on hospital-associated methicillin-resistant S aureus
      (HA-MRSA); however, a global epidemic because of virulent community-associated
      MRSA (CA-MRSA) that has no "fitness cost" for carrying antibiotic-resistance
      genes has moved into neonatal intensive care units (NICUs). Recently, methicillin
      susceptible S aureus has adopted some of the virulence factors of CA-MRSA and is
      an increasingly common cause of hospital-acquired infections in NICUs. This
      article reviews the changing epidemiology, clinical manifestations, and treatment
      of S aureus in neonates.

PMID- 20813270
TI  - Antibiotic resistance in neonatal intensive care unit pathogens: mechanisms,
      clinical impact, and prevention including antibiotic stewardship.
AB  - Antimicrobial-resistant pathogens are of increasing concern in the neonatal
      intensive care unit population. A myriad of resistance mechanisms exist in
      microorganisms, and management can be complex because broad-spectrum antibiotics
      are increasingly needed. Control and prevention of antibiotic-resistant organisms
      (AROs) require an interdisciplinary team with continual surveillance. Judicious
      use of antibiotics; minimizing exposure to risk factors, when feasible; and
      effective hand hygiene are crucial interventions to reduce infection and
      transmission of AROs.

PMID- 20813271
TI  - New concepts of microbial translocation in the neonatal intestine: mechanisms and
      prevention.
AB  - Bacterial translocation from the gastrointestinal tract is an important pathway
      initiating late-onset sepsis and necrotizing enterocolitis in very low-birth
      weight infants. The emerging intestinal microbiota, nascent intestinal epithelia,
      naive immunity, and suboptimal nutrition (lack of breast milk) have roles in
      facilitating bacterial translocation. Feeding lactoferrin, probiotics, or
      prebiotics has presented exciting possibilities to prevent bacterial
      translocation in preterm infants, and clinical trials will identify the most safe
      and efficacious prevention and treatment strategies.

PMID- 20813272
TI  - Heart rate characteristics: physiomarkers for detection of late-onset neonatal
      sepsis.
AB  - Early detection of late-onset neonatal sepsis, before the onset of obvious and
      potentially catastrophic clinical signs, is an important goal in neonatal
      medicine. Sepsis causes a well-known series of physiologic changes including
      abnormalities of blood pressure, respiration, temperature, and heart rate, and
      less well-known changes in heart rate variability. Although vital signs are
      frequently or continuously monitored in patients in the neonatal intensive care
      unit (NICU), changes in these parameters are subtle in the early phase of sepsis
      and difficult to interpret using traditional NICU monitoring tools. A new tool,
      continuous monitoring of heart rate characteristics (HRC), is now available for
      clinical use. Recent research has established that 2 abnormalities of HRC that
      have long been used by obstetricians to identify fetal compromise, reduced heart
      rate variability and transient decelerations, occur early in the course of sepsis
      in patients in the NICU, often before clinical signs of illness. Through
      mathematical modeling of electrocardiogram data from hundreds of patients in the
      NICU, an HRC index that represents the fold increase in risk that a neonate will
      be diagnosed with clinical or culture-proven sepsis within the next 24 hours was
      derived. The effect of continuous HRC monitoring on outcomes in preterm very low
      birth weight infants is the subject of a multicenter randomized clinical trial of
      3000 patients, which will be complete in 2010. Further research into mechanisms
      of abnormal HRC and regulation of autonomic nervous system function in sepsis and
      other disease processes will shed light on additional applications of this
      exciting new technology.

PMID- 20813273
TI  - Biomarkers for late-onset neonatal sepsis: cytokines and beyond.
AB  - Acute phase reactants, pro and antiinflammatory mediators including chemokines
      and cytokines, and cell-surface antigens are nonspecific biomarkers that have
      been extensively studied for the diagnosis and management of late-onset neonatal
      sepsis (LONS) and necrotizing enterocolitis. It is expected that the next
      generation of biomarkers and tests will be more specific, will pinpoint the
      precise disease entity, and will provide crucial information on the exact
      pathogen or category of microorganism and its antibiotic profile within hours of
      clinical presentation. Research on molecular pathogen detection and proteomic
      profiling has shown promising results. Academic-industry partnerships are vital
      for successful development of new diagnostic biomarkers for LONS, which are
      sensitive, inexpensive, fully automated, and easy to measure, allowing a quick
      turnaround time for clinical decision making.

PMID- 20813274
TI  - Strategies to prevent invasive candidal infection in extremely preterm infants.
AB  - The highest incidence of invasive candidal infection (ICI) occurs in extremely
      preterm infants (<1000 g birth weight and <or=27 weeks' gestation). In this
      population, ICI has high mortality, leads to significant neurodevelopmental
      impairment, and results in increased length of hospital stay and costs.
      Randomized clinical trials in infants of less than 1000 g birth weight have
      demonstrated that ICI is decreased 88% by antifungal prophylaxis with fluconazole
      compared to 54% by nystatin prophylaxis from retrospective studies. Fluconazole
      is more efficacious than nystatin prophylaxis in infants weighing less than 1000
      g, is less expense, requires less frequent dosing (twice weekly intravenous [IV]
      dosing), and can be given when infants are not feeding. While antifungal
      prophylaxis is inexpensive, cost-effective, and easy to administer, yet has not
      been instituted universally despite A-1 evidence from single and multicenter
      studies demonstrating efficacy and safety. Debate is ongoing over whether empiric
      therapy or improved infection control practices are superior to prophylaxis,
      whether prophylaxis should be instituted only in neonatal intensive care units
      (NICUs) with a relatively high ICI rate, and whether fluconazole prophylaxis is
      safe or risks emergence of resistance. To date, azole resistance has not emerged
      with targeted treatment of high-risk infants for the duration of IV catheter use.
      Empiric therapy for suspected ICI and standardized therapy for candidemia,
      including central venous catheter removal, may decrease mortality; however, these
      approaches still risk neurodevelopmental impairment in ICI survivors. Infection
      control practices have not been subjected to prospective or randomized trials to
      demonstrate efficacy in reducing fungal infections. Evidence is presented in this
      article from clinical trials demonstrating efficacy and safety of antifungal
      prophylaxis in preventing ICI in preterm infants. The greatest impact of
      antifungal prophylaxis preventing ICI and decreasing Candida-related mortality
      and neurodevelopmental impairment would be achieved with a universal approach in
      all NICUs.

PMID- 20813275
TI  - Strategies to prevent ventilator-associated pneumonia in neonates.
AB  - Ventilator-associated pneumonia (VAP) is one of the leading causes of preventable
      morbidity and mortality in neonatal intensive care units. This review examines
      the epidemiology and pathogenesis of VAP in neonates as well as the dilemmas
      faced by caregivers to diagnose and prevent VAP.

PMID- 20813276
TI  - Simple strategies to reduce healthcare associated infections in the neonatal
      intensive care unit: line, tube, and hand hygiene.
AB  - This article describes strategies to prevent 2 important healthcare associated
      infections in the neonatal intensive care unit: central line-associated
      bloodstream infections and catheter-associated urinary tract infections. Hand
      hygiene is discussed as the cornerstone for prevention of all healthcare
      associated infections. Specific recommendations for education and training of
      health care personnel who insert and maintain central venous catheters and
      urinary tract catheters are made and best practices for insertion and maintenance
      of these catheters are discussed. Throughout this article, the emphasis is on
      prevention of these high morbidity and mortality healthcare associated
      infections.

PMID- 20813277
TI  - Meningitis in neonates: bench to bedside.
AB  - The clinical outcome of central nervous system infection is determined by the
      characteristics of the pathogen and the brain's response to the invading
      bacteria. How infection leads to brain injury remains unresolved. An impediment
      to progress is the complexity of pathophysiologic processes. Some of the
      mechanisms involved have been identified in experimental models, providing
      insights into the molecular basis of brain injury and regeneration, and hinting
      at targets for therapy. Adjuvant therapies have been proposed. Interventions that
      protect the brain are evaluated for their potential to preserve neuro-integrative
      functions in long-term survivors of bacterial meningitis. This article summarizes
      current studies evaluating pharmacologic interventions in experimental models of
      bacterial meningitis and discusses how the knowledge gathered could translate
      into more effective therapies.

PMID- 20813278
TI  - Progress toward improved understanding of infection-related preterm birth.
AB  - Current strategies to prevent infection-related preterm birth and its associated
      neonatal morbidities have had limited success. Improved understanding of the
      pathogen-host interactions underlying altered colonization of the lower genital
      tract is necessary before significant progress can be made. The application of
      novel diagnostic techniques such as broad range PCR and proteomic analysis
      contribute to our knowledge of the diversity and abundance of microbial species
      invading the amniotic cavity as well as the resultant inflammatory response.
      Preterm infants delivered following intrauterine infection may respond
      differently to subsequent infectious challenges in the neonatal intensive care
      unit.

PMID- 20813279
TI  - Saddle pulmonary embolism visualized by transthoracic echocardiography.

PMID- 20813280
TI  - Age as a risk factor for stroke in atrial fibrillation patients: implications for
      thromboprophylaxis.
AB  - The prevalence of atrial fibrillation (AF) is related to age and is projected to
      rise exponentially as the population ages and the prevalence of cardiovascular
      risk factors increases. The risk of ischemic stroke is significantly increased in
      AF patients, and there is evidence of a graded increased risk of stroke
      associated with advancing age. Oral anticoagulation (OAC) is far more effective
      than antiplatelet agents at reducing stroke risk in patients with AF. Therefore,
      increasing numbers of elderly patients are candidates for, and could benefit
      from, the use of anticoagulants. However, elderly people with AF are less likely
      to receive OAC therapy. This is mainly due to concerns about a higher risk of OAC
      associated hemorrhage in the elderly population. Until recently, older patients
      were under-represented in randomized controlled trials of OAC versus placebo or
      antiplatelet therapy, and therefore the evidence base for the value of OAC in the
      elderly population was not known. However, analyses of the available trial data
      indicate that the expected net clinical benefit of warfarin therapy is highest
      among patients with the highest untreated risk for stroke, which includes the
      oldest age category. An important caveat with warfarin treatment is maintenance
      of a therapeutic international normalized ratio, regardless of the age of the
      patient, where time in therapeutic range should be > or =65%. Therefore, age
      alone should not prevent prescription of OAC in elderly patients, given an
      appropriate stroke and bleeding risk stratification.

PMID- 20813281
TI  - Differential associations between specific depressive symptoms and cardiovascular
      prognosis in patients with stable coronary heart disease.
AB  - OBJECTIVES: The purpose of this research was to evaluate the relationship between
      cognitive and somatic depressive symptoms and cardiovascular prognosis.
      BACKGROUND: Depression in patients with stable coronary heart disease (CHD) is
      associated with poor cardiac prognosis. Whether certain depressive symptoms are
      more cardiotoxic than others is unknown. METHODS: In the Heart and Soul Study,
      1,019 patients with stable CHD were assessed using the Patient Health
      Questionnaire to determine the presence of the 9 depressive symptoms included in
      the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition. The
      mean age of the patients was 67 years, and 82% were men. A comparison was made on
      a new cardiovascular event (myocardial infarction, stroke, transient ischemic
      attack, or congestive heart failure) or death (mean follow-up duration 6.1 +/-
      2.0 years) on the basis of cognitive and somatic sum scores and for patients with
      or without each of those specific depressive symptoms. Demographic
      characteristics, cardiac risk factors, and cardiac medications were controlled
      for. RESULTS: After adjustment for demographic data and cardiac risk factors,
      each somatic symptom was associated with 14% greater risk for events (hazard
      ratio [HR]: 1.14; 95% confidence interval [CI]: 1.05 to 1.24; p = 0.002). Fatigue
      (HR: 1.34; 95% CI: 1.07 to 1.67; p = 0.01), appetite problems (HR: 1.46; 95% CI:
      1.12 to 1.91; p = 0.005), and sleeping difficulties (HR: 1.26; 95% CI: 1.00 to
      1.58; p = 0.05) were most strongly predictive of cardiovascular events. In
      contrast, cognitive symptoms (HR: 1.08; 95% CI: 0.99 to 1.17; p = 0.09) were not
      significantly associated with cardiovascular events. CONCLUSIONS: In patients
      with stable CHD, somatic symptoms of depression were more strongly predictive of
      cardiovascular events than cognitive symptoms, although the CIs surrounding these
      estimates had substantial overlap. These findings are highly consistent with
      those of previous studies. Further research is needed to understand the
      pathophysiological processes by which somatic depressive symptoms contribute to
      prognosis in patients with CHD.

PMID- 20813283
TI  - Hemodynamic basis of exercise limitation in patients with heart failure and
      normal ejection fraction.
AB  - OBJECTIVES: The purpose of this study was to invasively investigate the
      hemodynamic response to exercise in patients with heart failure with normal
      ejection fraction (HFNEF) and to evaluate the ability of the peak early diastolic
      transmitral velocity to peak early diastolic annular velocity ratio (E/e') to
      reflect exercise hemodynamics. BACKGROUND: There is little information regarding
      the hemodynamic response to exercise in HFNEF. METHODS: Patients with HFNEF (n =
      14) and asymptomatic controls (n = 8) underwent right-side heart catheterization
      at rest and during supine cycle ergometer exercise and echocardiography with
      measurement of resting and peak exercise E/e'. RESULTS: Resting pulmonary
      capillary wedge pressure (PCWP) (10 +/- 4 mm Hg vs. 10 +/- 4 mm Hg; p = 0.94) was
      similar in HFNEF patients and controls, but stroke volume index (SVI) (p = 0.02)
      was lower, and systemic vascular resistance index (SVRI) (p = 0.01) was higher in
      patients. Patients stopped exercise at lower work rate (0.63 +/- 0.29 W/kg vs.
      1.13 +/- 0.49 W/kg; p = 0.006). Although peak exercise PCWP was similar in both
      groups (23 +/- 6 mm Hg vs. 20 +/- 7 mm Hg; p = 0.31), the peak PCWP/work rate
      ratio was higher in patients compared with controls (46 +/- 31 mm Hg/W/kg vs. 20
      +/- 9 mm Hg/W/kg; p = 0.03). Peak exercise SVI (p = 0.001) was lower and SVRI was
      higher (p = 0.01) in patients. Resting E/e' was modestly elevated in patients
      (13.2 +/- 4.1 vs. 9.5 +/- 3.4; p = 0.04). Peak exercise E/e' did not differ
      between the groups (11.1 +/- 3.4 vs. 9.4 +/- 3.4; p = 0.28). CONCLUSIONS: The
      HFNEF patients achieved a similar peak exercise PCWP to that of asymptomatic
      controls, at a much lower workload. This occurs at a lower SVI and in the setting
      of higher SVRI. The E/e' does not reflect the hemodynamic changes during exercise
      in HFNEF patients.

PMID- 20813282
TI  - Global cardiovascular reserve dysfunction in heart failure with preserved
      ejection fraction.
AB  - OBJECTIVES: The purpose of this study was to comprehensively examine
      cardiovascular reserve function with exercise in patients with heart failure and
      preserved ejection fraction (HFpEF). BACKGROUND: Optimal exercise performance
      requires an integrated physiologic response, with coordinated increases in heart
      rate, contractility, lusitropy, arterial vasodilation, endothelial function, and
      venous return. Cardiac and vascular responses are coupled, and abnormalities in
      several components may interact to promote exertional intolerance in HFpEF.
      METHODS: Subjects with HFpEF (n = 21), hypertension without heart failure (n =
      19), and no cardiovascular disease (control, n = 10) were studied before and
      during exercise with characterization of cardiovascular reserve function by
      Doppler echocardiography, peripheral arterial tonometry, and gas exchange.
      RESULTS: Exercise capacity and tolerance were reduced in HFpEF compared with
      hypertensive subjects and controls, with lower VO(2) and cardiac index at peak,
      and more severe dyspnea and fatigue at matched low-level workloads. Endothelial
      function was impaired in HFpEF and in hypertensive subjects as compared with
      controls. However, blunted exercise-induced increases in chronotropy,
      contractility, and vasodilation were unique to HFpEF and resulted in impaired
      dynamic ventricular-arterial coupling responses during exercise. Exercise
      capacity and symptoms of exertional intolerance were correlated with
      abnormalities in each component of cardiovascular reserve function, and HFpEF
      subjects were more likely to display multiple abnormalities in reserve.
      CONCLUSIONS: HFpEF is characterized by depressed reserve capacity involving
      multiple domains of cardiovascular function, which contribute in an integrated
      fashion to produce exercise limitation. Appreciation of the global nature of
      reserve dysfunction in HFpEF will better inform optimal design for future
      diagnostic and therapeutic strategies.

PMID- 20813284
TI  - Culprit Mechanism(s) for Exercise Intolerance in Heart Failure With Normal
      Ejection Fraction.

PMID- 20813286
TI  - On the evolution of the fontan operation: from an electrophysiologist's
      perspective.

PMID- 20813285
TI  - Arrhythmias in a contemporary fontan cohort: prevalence and clinical associations
      in a multicenter cross-sectional study.
AB  - OBJECTIVES: Our aim was to examine the prevalence of arrhythmias and identify
      independent associations of time to arrhythmia development. BACKGROUND: Since
      introduction of the Fontan operation in 1971, long-term results have steadily
      improved with newer modifications. However, atrial arrhythmias are frequent and
      contribute to ongoing morbidity and mortality. Data are lacking regarding the
      prevalence of arrhythmias and risk factors for their development in the current
      era. METHODS: The Pediatric Heart Network Fontan Cross-Sectional study evaluated
      data from 7 centers, with 520 patients age 6 to 18 years (mean 8.6 +/- 3.4 years
      after the Fontan operation), including echocardiograms, electrocardiograms,
      exercise testing, parent-reported Child Health Questionnaire (CHQ) results, and
      medical history. RESULTS: Supraventricular tachycardias were present in 9.4% of
      patients. Intra-atrial re-entrant tachycardia (IART) was present in 7.3% (32 of
      520). The hazard of IART decreased until 4 to 6 years post-Fontan, and then
      increased with age thereafter. Cardiac anatomy and resting heart rate (including
      marked bradycardia) were not associated with IART. We identified 3 independent
      associations of time to occurrence of IART: lower CHQ physical summary score (p <
      0.001); predominant rhythm (p = 0.002; highest risk with paced rhythm), and type
      of Fontan operation (p = 0.037; highest risk with atriopulmonary connection).
      Time to IART did not differ between patients with lateral tunnel and extracardiac
      conduit types of Fontan repair. Ventricular tachycardia was noted in 3.5% of
      patients. CONCLUSIONS: Overall prevalence of IART was lower in this cohort (7.3%)
      than previously reported. Lower functional status, an atriopulmonary connection,
      and paced rhythm were determined to be independently associated with development
      of IART after Fontan. (Relationship Between Functional Health Status and
      Ventricular Performance After Fontan-Pediatric Heart Network; NCT00132782).

PMID- 20813287
TI  - Ebstein's anomaly with left ventricular noncompaction and bicuspid aortic valve.

PMID- 20813288
TI  - President's page: the ACC reconfirms commitment to transparent relationships with
      industry.

PMID- 20813289
TI  - Importance of providing cardiologists with useful advice on herb-drug
      interactions.

PMID- 20813290
TI  - Herbal products review: what do we really know?

PMID- 20813291
TI  - Herbal products review provides inaccurate information on dietary supplement
      regulations.

PMID- 20813294
TI  - High signal intensity in the dural sinuses on 3D-TOF MR angiography at 3.0 T.
AB  - PURPOSE: The objective of this study was to examine the frequency of high signal
      intensity in the dural sinuses of normal subjects upon magnetic resonance (MR)
      angiography using 3.0-T scanners. METHODS: A total of 748 consecutive healthy
      subjects underwent three-dimensional time-of-flight MR angiography at 3.0 T.
      Sixteen subjects were excluded. MR angiographic source images were
      retrospectively reviewed for the presence of high signal intensity in the
      inferior petrosal sinus, pterygoid sinus, or sigmoid sinus. RESULTS: Of the 732
      examinations, 10 (1.3%) showed high signal intensity in the dural sinuses (left
      inferior petrosal sinus, n=4; left pterygoid sinus, n=3; left sigmoid sinus,
      n=6). High signal intensity in the dural sinuses was observed only on the left
      side. The minimum diameter of the left brachiocephalic vein was significantly
      smaller in subjects with high signal intensity than in the control group.
      CONCLUSION: In our study with healthy subjects at 3.0 T, the frequency of high
      signal intensity in the dural sinuses is as low as 1.3%. Retrograde flow due to
      physiological stenosis of the left brachiocephalic vein may be one of the causes
      of this phenomenon.

PMID- 20813293
TI  - Cerebral pulsatility index by transcranial Doppler sonography predicts the
      prognosis of patients with fulminant hepatic failure.
AB  - AIM: Cerebral hemodynamic derangement is well known in patients with fulminant
      hepatic failure. The advent of transcranial Doppler sonography (TCD) enabled
      noninvasive observation of cerebral hemodynamics. To evaluate its clinical
      usefulness, we examined longitudinal cerebral hemodynamic parameters in patients
      with fulminant hepatic failure and severe acute hepatitis. METHODS: The six
      subjects were four patients with fulminant hepatic failure, one with severe acute
      hepatitis and one with severe acute exacerbation on chronic hepatitis. The
      pulsatility indices of the right middle cerebral artery were used as parameters
      of cerebral hemodynamics. RESULTS: The pulsatility indices of the two patients
      with a deteriorating course had elevated to >1.00, whereas those of the two
      patients undergoing recovery were within normal limits, as well as of the
      patients with acute hepatitis or acute exacerbation on chronic hepatitis.
      CONCLUSION: Cerebral pulsatility measured by TCD may be a real-time and useful
      tool to assess and monitor patients with fulminant hepatic failure.

PMID- 20813295
TI  - Anomalous origin of the coronary arteries in children: diagnostic role of three
      dimensional coronary MR angiography.
AB  - When the anomalous origin of coronary arteries (AOCA) is suspected in children
      (especially athletes), due to signs and symptoms of myocardial ischemia or on the
      basis of echocardiographic assessment, three-dimensional coronary magnetic
      resonance angiography (3D-CMRA) can be proposed for the fine morphological
      evaluation of coronary branches anatomy and course. We tested the diagnostic
      potential of CMRA angiography in a prospective study on AOCA in young patients.
      Between July 2005 and June 2008, 15 patients aged 6-29 years (mean age, 13.5
      years+/-5.6 S.D.; median, 14) with clinical and echocardiographic suspicion of
      AOCA underwent CMRA (1.5 T), 3D whole-heart, free-breathing technique, without
      the use of contrast medium and beta-blockers, with a mean examination time of 30
      min. We acquired a second scan of all patients to ameliorate the quality of the
      acquisition and to improve our experience. AOCA was confirmed by 3D-CMRA in 8 out
      of 15 cases (53%) and three different anatomical variants were demonstrated, that
      is, ectopic origin of the left circumflex artery arising from the right coronary
      artery with retro-aortic course in four cases, single coronary artery arising
      from the right sinus of Valsalva with interarterial course in one case, ectopic
      right coronary artery arising from the left sinus of Valsalva with interarterial
      course in one case; in two patients without anomalies of origin of the coronary
      arteries, elongated LMCA with angulation of the proximal segment of the left
      circumflex artery was present. When AOCA is suspected particularly in children
      (especially athletes), CMRA without the use of contrast medium is an effective
      diagnostic technique, which is useful to clarify the spatial position of the
      anomalous course of the main coronary branches in order to suggest the most
      convenient management of the disease. CMRA does not need contrast medium,
      needles, and beta-blockers; is repeatable in the same examination without the
      exposure to X-rays; allows a parent to stay near the child; and needs low
      collaboration in low-stress conditions.

PMID- 20813296
TI  - Radiological features of acute gastric volvulus in adult patients.
AB  - OBJECTIVE: To evaluate the radiological features of acute gastric volvulus in
      adults and correlate these features with operative findings. MATERIALS AND
      METHODS: The clinical, radiological and operative findings of five adult patients
      (four males and one female with mean age of 50.4 years) who presented or referred
      to King Abdullah University hospital over 4 year's period with symptoms of acute
      gastric volvulus were reviewed retrospectively. All patients underwent upper
      gastrointestinal barium study and two of them had computed tomographic (CT) scans
      preoperatively. The radiological features demonstrated on upper gastrointestinal
      barium exams and CT scans were analyzed and compared with operative findings.
      RESULTS: Radiological and operative findings revealed organo-axial gastric
      volvulus in all patients in our study. All of them had associated diaphragmatic
      defect or hiatal hernia. The upper gastrointestinal barium studies demonstrated
      the classic radiological features of organo-axial volvulus. CT done on two of our
      patients confirmed the diagnosis. CONCLUSION: Upper gastrointestinal barium study
      is an accurate way to diagnose and characterize acute gastric volvulus in adult
      patients. CT scan can also be used to diagnose this clinical entity.

PMID- 20813297
TI  - Impact of age on FDG uptake in the liver on PET scan.
AB  - PURPOSE: The intensity of physiological 18F-2-deoxy-D-glucose (FDG) uptake in the
      liver varies. It is important to be familiar with the varying degree of FDG
      accumulation in the liver that represents normal distribution and physiological
      changes, before attempting to interpret whole-body positron emission tomography
      (PET) imaging for malignancy detection. The aim of this study is to evaluate the
      possible factors influencing the intensity of physiological FDG uptake in the
      liver on FDG PET imaging. MATERIALS AND METHODS: From 2005 to 2007, a total of
      339 consecutive healthy subjects, referred from the Department of Community
      Medicine and Health Examination Center of our hospital for health screening, were
      retrospectively recruited for analysis. Demographic data were collected from
      chart records. Whole body FDG PET imaging and serologic determination of
      hepatitis B virus (HBV) and hepatitis C virus (HCV) infection status were
      performed on all subjects. The mean and maximum standard uptake values (SUVs) of
      the liver were calculated. The relationships between sex, age, HBV and HCV
      infection status, and SUVmax and SUVmean of the liver on FDG PET imaging were
      evaluated. RESULTS: There was no statistically significant relationship between
      sex, HBV and HCV infection status and maximum standard uptake value (SUVmax) or
      mean standard uptake value (SUVmean) of the liver. After adjusting for
      covariables, age was a statistically significant predictor of SUVmax (B=0.18; P=
      .001) and SUVmean (B=0.16; P= .004) of the liver on FDG PET imaging. CONCLUSION:
      Age has a significant and positive impact on both maximum and mean standard
      uptake values of the liver on FDG PET imaging. High physiological background FDG
      uptake will reduce diagnostic sensitivity and accuracy for malignancy detection
      in the liver.

PMID- 20813298
TI  - Characterization of pancreatic metastases from primary lung cancer using magnetic
      resonance imaging.
AB  - AIM: To evaluate magnetic resonance (MR) imaging of pancreatic metastases
      secondary to primary lung cancers. MATERIALS AND METHODS: Eleven cases included
      T1-weighted, T2-weighted, and spectral presaturation attenuated inversion
      recovery T2-weighted images. RESULTS: Of the 21 total pancreatic lesions
      evaluated, 10 exhibited a peripheral rim of high signal intensity, 9 displayed a
      homogeneous signal intensity, and 2 lesions demonstrated a heterogeneous pattern
      of contrast enhancement. CONCLUSION: Limitations in evaluating pancreatic
      metastases by MR imaging require definitive diagnoses to rely on both clinical
      data and MR imaging.

PMID- 20813299
TI  - Flow turbulence or twinkling artifact? A primary observation on the intrarenal
      color Doppler sonography.
AB  - OBJECTIVE: The objective of this report was to describe and potentially explain
      differences of intrarenal color Doppler sonography (CDUS) manifestations between
      blood flow turbulence and twinkling artifact. METHODS: We retrospectively
      reviewed 32 cases with appearance of focally increased color Doppler signal on
      intrarenal CDUS from May 1, 2007, to February 28, 2009. Indications for
      intrarenal CDUS in 32 cases were suspicion of renovascular hypertension,
      investigation of complications related to renal biopsy, or hematuria.
      Characteristics of the color Doppler signal, relationship between color Doppler
      signal and renal vessels, and the spectral Doppler sampled at the anatomic site
      of the focal color signal were analyzed. The value and pitfall of color Doppler
      in the diagnosis of the intrarenal vascular abnormality and detection of renal
      calculus are discussed. RESULTS: Thirty-two cases with focally increased color
      Doppler during sonography of native or transplanted kidneys were classified into
      two groups: (1) turbulent blood flow-intrarenal vascular abnormalities including
      intrarenal arteriovenous fistula (15 cases) and intrarenal artery stenosis (eight
      cases); and (2) color Doppler artifact-twinkling produced by renal calculus (nine
      cases). There were differences in the characteristics of the color Doppler
      signal, the relationship between the color signal and renal vessel, and the
      spectral waveform on CDUS between flow turbulence and twinkling. CONCLUSION: Flow
      turbulence and twinkling artifact on intrarenal CDUS are distinguishable by
      analyzing the manifestations on intrarenal CDUS. Proper color Doppler setting and
      spectral Doppler play important roles in differentiation between flow turbulence
      in renal vascular abnormalities and twinkling produced by renal stones.

PMID- 20813300
TI  - Detection of lymph nodes in pelvic malignancies with Computed Tomography and
      Magnetic Resonance Imaging.
AB  - Thirty patients with prostate or bladder cancer underwent CT and MRI for nodal
      staging. CT detected 189 nodes, and MRI detected 271 nodes. This difference was
      statistically significant in the external iliac (CT/MRI=73/87 nodes), obturator
      (CT/MRI=48/75 nodes), and internal iliac (CT/MRI=24/46 nodes) nodal chains. Based
      on size, the number of nodes detected by CT and MRI were as follows: 1-5 mm,
      CT/MRI=91/166; 6-10 mm, CT/MRI=91/98; >10 mm, CT/MRI=7/7 nodes. MRI detected
      significantly more lymph nodes in the size range of 1-5 mm.

PMID- 20813302
TI  - Dynamic close-mouth view radiograph method for the diagnosis of lateral dynamic
      instability of the atlantoaxial joint.
AB  - The purpose of the current study is to establish the dynamic close-mouth view
      radiograph method. Seven healthy volunteers were enrolled. Dynamic open-mouth and
      close-mouth view radiographs were obtained. The odontoid lateral mass interval
      and the dynamic atlantodental lateral shift (ADLS) were measured. The ADLS was
      9.4+/-5.3% by the close-mouth view, showing a significantly greater percentage
      than that of 5.3+/-4.0% by the open-mouth view. The dynamic close-mouth view can
      be useful for diagnosis of atlantoaxial lateral instability.

PMID- 20813301
TI  - Graph-matching-based computed tomography angiography in peripheral arterial
      occlusive disease.
AB  - The objective of this study is to compare a graph-matching-based software and a
      conventional tool for postprocessing of computed tomography angiography (CTA) in
      correlation with the gold standard digital subtraction angiography. Sensitivity,
      specificity, accuracy, and interobserver agreement increased from 80.3% to 92.9%,
      from 69.1% to 92.4%, from 73.5% to 92.8%, and from 0.45 to 0.96, respectively,
      using the graph-matching-based technique. Graph-matching-based CTA increases
      sensitivity, specificity, accuracy, and interobserver agreement in comparison to
      a conventional bone elimination tool in the assessment of peripheral arterial
      occlusive disease.

PMID- 20813303
TI  - An unusual case of primary mesenchymal chondrosarcoma in orbit with intracranial
      extension.
AB  - An unusual case of primary orbital mesenchymal chondrosarcoma with intracranial
      extension is reported, with special emphasis on the radiological findings.

PMID- 20813304
TI  - Melanotic neuroectodermal tumor of infancy: report of one calvarial lesion with
      T1 shortening and one maxillary lesion.
AB  - Melanotic neuroectodermal tumor of infancy (MNTI) is a rare tumor which commonly
      involves the mandible, maxilla and calvarium. We report two infants with this
      rare tumor. T1 shortening due to melanin content has been rarely described in
      MNTI. The calvarial MNTI showed T1 shortening which was helpful in diagnosis.

PMID- 20813305
TI  - Use of a hemostasis introducer sheath to guide clip delivery during stereotactic
      directional vacuum-assisted breast biopsy when the biopsy system malfunctions.
AB  - Stereotactic directional vacuum-assisted breast biopsy (ST DVAB) is an accurate
      biopsy method. Marking the biopsy site with a clip is mandatory after ST DVAB, in
      case excision is required. With the ST DVAB system we use, clip was delivered
      through the biopsy probe. We report a case with malfunctioning of the ST DVAB
      system during the procedure, and thus the clip could not be placed through the
      biopsy probe. To salvage the procedure, we placed the clip to the biopsy site via
      a hemostasis introducer sheath.

PMID- 20813306
TI  - Kikuchi-Fujimoto disease with spontaneous subdural hematoma in a middle-aged
      Hispanic male.
AB  - Kikuchi-Fujimoto disease (KFD) is an uncommon disorder that usually presents in
      young adults of Asian descent with fever and cervical lymphadenopathy.
      Clinically, this disease is often misdiagnosed as lymphoma or tuberculosis, and
      biopsy is needed for confirmation. The authors report an unusual case of KFD in a
      Hispanic male presenting with a subacute subdural hematoma, whose care was
      complicated by extranodal features not typically associated with KFD. The
      clinical, histopathologic, and radiographic manifestations of KFD are discussed.

PMID- 20813307
TI  - False positive for malignancy of a lung nodule on FDG PET/CT scans--a lesion with
      high FDG uptake but stable in size.
AB  - A highly F-18 fluorodeoxyglucose-avid lung nodule was stable in both size and
      metabolic activity over 4 months. This was most likely nonneoplastic because a
      true tumor would grown in volume overtime. The high level of energy consumption
      was contributing functional activities or by inflammatory cells. Because the
      speed of tumor growth is proportional to its energy consumption, we consider the
      higher the metabolic activity of a lesion, the less likely of malignant if it was
      stable in size over time.

PMID- 20813308
TI  - Ground-glass nodules found in two patients with malignant melanomas: different
      growth rate and different histology.
AB  - We report two pathologically proven pure ground-glass nodules found in two
      patients with malignant melanoma. In one patient, the nodule showed no growth
      over 2 months and was found to be bronchioloalveolar carcinoma, whereas in the
      other patient, a nodule grew rapidly over 3 months and was histologically
      confirmed to be metastatic melanoma.

PMID- 20813309
TI  - Radiologic findings of lung lobe torsion in reconstructed multidetector computed
      tomography image lead to early detection.
AB  - Torsion of the remaining lung lobe after lobectomy is a rare complication, and
      sometimes, diagnosis can be difficult. But early detection is important to
      prevent resection and fatal complication. We present a case of left lower lobe
      torsion with reconstructed image of multidetector computed tomography (MDCT)
      findings, which propose a possibility of early detection on retrospective review
      after surgical reduction. Multiplanar reconstruction of MDCT image, 3-dimensional
      CT angiography, and CT bronchography could provide important diagnostic clues.

PMID- 20813310
TI  - Emerging treatment for stage I non-small cell lung cancer: introduction.

PMID- 20813311
TI  - Risk assessment for pulmonary resection.
AB  - Risk assessment for pulmonary resection must include a preliminary cardiac
      evaluation. Patients deemed at prohibitive cardiac risk should be evaluated and
      treated as per American Heart Association/American Society of Cardiology
      guidelines. Those with low cardiac risk or with optimized treatment can proceed
      with pulmonary assessment. A systematic measurement of lung carbon monoxide
      diffusing capacity is recommended. In addition, predicted postoperative forced
      expiratory volume in 1 second should not be used alone for patient selection
      because it is not an accurate predictor of complications, particularly in
      patients with chronic obstructive pulmonary disease. The use of exercise testing
      should be emphasized. Low-technology tests, such as stair climbing, can be used
      whenever a formal cardiopulmonary exercise test is not readily available.
      However, in case of suboptimal performance (ie, <22 m in the stair-climbing test)
      patients should be referred to cardiopulmonary exercise testing with measurement
      of Vo(2max) for a better definition of their aerobic reserve. A Vo(2max) less
      than 10 mL/kg/min (or <35% of predicted) indicates a high risk for major lung
      resection.

PMID- 20813312
TI  - Thoracoscopic lobectomy for stage I non-small cell lung cancer.
AB  - Lobectomy via video-assisted thoracoscopic surgery (VATS) has a lower rate of
      morbidity and is less immunosuppressive than open lobectomy. Compared with open
      lobectomy, VATS lobectomy appears to have equivalent oncological results. We
      review the literature on perioperative outcomes, biological impact, and
      oncological results. Most published reports to date--although retrospective-
      suggest significant perioperative advantages to VATS lobectomy over open
      lobectomy. Data on acute phase reactants and cellular immunity show that VATS
      lobectomy causes less of an inflammatory response and is less immunosuppressive
      than open lobectomy. Mid- to long-term oncological results of patients with early
      stage non-small cell lung cancer (NSCLC) appear to be equivalent for VATS and
      open lobectomy. Clinical evidence indicates that VATS lobectomy for early-stage
      NSCLC is associated with fewer postoperative complications and less negative
      biological impact than open lobectomy. Furthermore, all data to date strongly
      suggest oncological equivalence between VATS and open lobectomy for patients with
      early-stage NSCLC.

PMID- 20813313
TI  - Sublobar resection for early-stage lung cancer.
AB  - The use of sublobar resection techniques (anatomic segmentectomy; extended wedge)
      in the treatment of early-stage non-small cell lung cancer has been associated
      with increased local recurrence rates compared with lobectomy. Recent data,
      however, have suggested that sublobar resection of smaller tumors (especially
      those < or =2 cm) can be performed with no significant difference in local
      recurrence or long-term survival. These findings have particular relevance in
      elderly patients and in those patients who may be at high risk for lobectomy
      because of underlying medical comorbidities. Careful patient selection on the
      basis of individualized assessment of specific patient and tumor characteristics
      will aid in selecting the optimal approach. For larger tumors, or when adequate
      surgical margins are not obtainable, lobectomy should be performed. Currently,
      active, prospective, randomized studies (Cancer and Leukemia Group B [CALGB]
      140503 and American College of Surgeons Oncology Group [ACOSOG] Z4032) will
      provide critical insights in delineating the efficacy of sublobar resection
      techniques in early-stage non-small cell lung cancer.

PMID- 20813314
TI  - Sublobar resection with brachytherapy mesh for stage I non-small cell lung
      cancer.
AB  - Lobar resection is currently the standard approach for the treatment of stage I
      non-small cell lung cancer. Sublobar resection is generally considered a
      compromise, reserved for high-risk patients because of greater rates of local
      recurrence compared with lobar resection. Adjuvant radiation therapy may decrease
      these increased local recurrence rates, but because of respiratory motion and
      difficulties in identifying the staple line, radiation delivery can be
      challenging with an external beam approach. Adjuvant intraoperative brachytherapy
      with the use of low-dose rate iodine-125 seeds placed alongside the surgical
      staple has been used with success in several centers. A randomized multicenter
      North American study has also recently completed accrual, but the results of this
      are not yet available. In the following review, we outline the techniques used,
      safety considerations, and currently available outcomes of sublobar resection
      with adjuvant brachytherapy for non-small cell lung cancer.

PMID- 20813315
TI  - Surgical resection in combination with lung volume reduction surgery for stage I
      non-small cell lung cancer.
AB  - Surgical resection remains the favored option of treatment for stage I lung
      cancer patients. Co-existing obstructive lung disease can reduce lung function
      and increase the risk of surgery. Severe emphysema may preclude resection of lung
      cancer due to concerns about low values of postoperative lung function. However,
      many patients will experience stable or improved lung function simply by
      resecting hyper-expanded and relatively functionless lung. This so-called "lung
      volume reduction effect" may occur after standard resection or after rare
      instances of formal lung volume reduction surgery concurrent with pulmonary
      resection of the tumor. This review explores these possibilities and informs the
      readers of pioneering work in this area.

PMID- 20813316
TI  - Fractionated radiotherapy for high-risk patients with early-stage non-small cell
      lung cancer.
AB  - The treatment of patients with early-stage non-small cell lung cancer and
      cardiopulmonary dysfunction has rapidly evolved during the past decade. Although
      fractionated radiotherapy has been the most frequently used alternative
      treatment, additional approaches, including limited resection with or without
      brachytherapy, stereotactic body radiotherapy, and radiofrequency ablation are
      increasingly used and have now been studied prospectively. This review will focus
      on the potential current role of fractionated radiotherapy for high-risk patients
      with particular consideration of altered fractionation schemes and recent
      advances in treatment related technology.

PMID- 20813317
TI  - Image-guided radiofrequency ablation for the treatment of early-stage non-small
      cell lung neoplasm in high-risk patients.
AB  - Lung cancer is the most common cause of cancer-related mortality in the United
      States. Surgical resection with a lobectomy is the standard treatment for stage I
      non-small cell lung cancer. With an aging population, however, there are a
      significant number of patients who have other comorbidities that preclude
      surgical resection. Image-guided radiofrequency ablation is a new emerging
      modality of treatment which may be applicable in this high-risk group of
      patients. In this article, we review the principles of radiofrequency ablation,
      the common devices in use, the results of ablate and resect studies, future
      directions, and the results of treatment for stage I non-small cell lung
      neoplasm.

PMID- 20813318
TI  - Stereotactic radiosurgery for lung tumors.
AB  - Lung cancer remains the most common cause of cancer-related deaths in the United
      States, and although surgery remains the standard treatment for early-stage
      tumors, stereotactic radiation is gaining an increasing role as an alternative
      form of therapy. Initially a form of treatment designed for neurosurgical
      applications, during the past decade stereotactic radiosurgery (SRS) has gone
      from a novel treatment for patients deemed to be prohibitive candidates for
      surgical resection to the point that there is now an international, randomized,
      multicenter trial to compare SRS to lobectomy in otherwise-healthy patients. This
      article reviews the history of SRS as applied to lung tumors, summarizes the
      currently available data on efficacy and toxicity, and describes some of the
      current controversial aspects of this treatment.

PMID- 20813319
TI  - Functional tricuspid regurgitation: introduction.

PMID- 20813320
TI  - Functional tricuspid regurgitation in mitral valve disease: epidemiology and
      prognostic implications.
AB  - In this review we summarize the data on epidemiology and natural history of
      functional tricuspid valve regurgitation as it applies to surgery for mitral
      valve disease. Tricuspid regurgitation in the context of mitral valve disease is
      frequent and is associated with substantial reduction in survival and quality of
      life. In many patients, the correction of left-sided cardiac lesions does not
      lead to resolution of tricuspid regurgitation. Significant tricuspid
      regurgitation after mitral valve surgery portends a poor prognosis, a course that
      is often not altered by subsequent surgical therapy. Although a liberal approach
      to tricuspid annuloplasty is widely practiced, the evidence that this approach
      alters the natural history of functional tricuspid regurgitation is not yet
      available, so it is not certain how much of the negative impact of tricuspid
      regurgitation is causative, rather than confounding, and to what degree we will
      improve long-term outcomes of mitral valve surgery by liberal tricuspid
      annuloplasty.

PMID- 20813321
TI  - The pathogenesis of functional tricuspid regurgitation.
AB  - Functional tricuspid regurgitation (TR) is a common etiology of TR. Functional TR
      results from geometrical distortion of the normal spatial relationships of the
      tricuspid leaflets, annulus, chords, papillary muscles, and right ventricular
      (RV) walls. Functional TR results most commonly from left-sided heart disease,
      including mitral valve abnormalities and cardiomyopathy and RV dysfunction
      secondary to pulmonary disease (Cor pulmonale). The tricuspid annulus, which has
      a normal bimodal or saddle shape, becomes larger, flatter, and more circular with
      the development of functional TR. RV dilation can lead to papillary muscle
      displacement and tethering of the tricuspid leaflets, resulting in incomplete
      coaptation and development of functional TR.

PMID- 20813322
TI  - Basis for intervention on functional tricuspid regurgitation.
AB  - Functional tricuspid regurgitation is a complex valvular lesion. Its optimal
      management remains controversial in the current era as the result of
      uncertainties regarding accurate diagnosis, surgical indication, the appropriate
      surgical procedure, and the late results of surgical treatment. It is no longer
      regarded a benign problem and does not resolve spontaneously after correction of
      left-sided heart valve lesions as once believed. It carries a significant
      morbidity and has an adverse impact on survival. Current techniques to repair
      functional tricuspid regurgitation are associated with a significant degree of
      residual or recurrent regurgitation mainly because of failure to address all the
      components of this challenging entity. This review article highlights emerging
      concepts and advances that provide an insight into the understanding of this
      perplexing lesion and attempts to define the basis of intervention on functional
      tricuspid regurgitation.

PMID- 20813323
TI  - Valve repair for functional tricuspid valve regurgitation: anatomical and
      surgical considerations.
AB  - Functional tricuspid regurgitation (TR) primarily arises from asymmetric dilation
      of the tricuspid annulus in the setting of right ventricular dysfunction and
      enlargement in response to left-sided myocardial and valvular abnormalities. Even
      if TR is not severe at the time of mitral valve surgery, TR can worsen and even
      appear late after successful mitral valve surgery, which portends a poor
      prognosis. Despite data demonstrating inferior outcomes in the presence of
      residual TR, surgical repair for functional TR remains underused. However,
      "benign neglect" of TR, especially in the presence of tricuspid annular dilation,
      is unacceptable. Surgical repair should consist of placement of a rigid or
      semirigid annular ring, which has been shown to provide superior durability
      compared with suture and flexible band-based therapies. Finally, minimally
      invasive and percutaneous approaches for correcting functional TR may increase
      the delivery of therapy and allow treatment of patients with recurrent TR at high
      risk for reoperation.

PMID- 20813324
TI  - Surgical strategies for functional tricuspid regurgitation.
AB  - Functional or secondary tricuspid regurgitation commonly is found in the setting
      of left-sided heart disease and, when severe, is associated with substantially
      poorer functional outcomes and survival if untreated. The traditional view that
      functional tricuspid regurgitation generally resolves with surgical correction of
      the primary lesions is no longer held. Data showing late development of severe
      tricuspid regurgitation in patients with mild regurgitation at time of mitral
      valve surgery have heralded a new era of aggressive intervention on the tricuspid
      valve. Tricuspid ring annuloplasty can be performed with minimal incremental
      morbidity and negligible additional mortality. Therefore, in addition to patients
      with severe regurgitation, annuloplasty is now also recommended for patients with
      risk factors for developing late tricuspid insufficiency (typically patients with
      moderate tricuspid regurgitation or severe annular dilation at time of left-sided
      cardiac procedures). In this work we review the current indications for tricuspid
      valve repair in patients undergoing other cardiac surgery operations and also the
      various options available to the surgeon.

PMID- 20813325
TI  - Durability of functional tricuspid valve repair.
AB  - Current tricuspid repair techniques have variable and disappointing durability.
      The authors of several studies have shown the superiority of ring (rather than
      suture or pericardial) annuloplasties; however, others suggest equal or superior
      results with suture or pericardial repair techniques. Indeed, recurrent
      significant tricuspid regurgitation has been reported consistently after repair;
      it is therefore unclear which technique provides the best long-term outcomes and
      in which patients. In this study, we evaluated the outcomes of different
      tricuspid repairs regarding durability and analyzed the risk factors for repair
      failure. We also presented our current approach to surgical management of
      functional tricuspid regurgitation on the basis of recent studies and our
      experience treating patients with heart failure.

PMID- 20813327
TI  - Tamoxifen as first-line treatment in a premenarchal girl with juvenile breast
      hypertrophy.
AB  - BACKGROUND: Juvenile breast hypertrophy is uncommon and is characterized by
      excessive breast enlargement in the peripubertal period. The clinical entity is
      thought to result from increased sensitivity of mammary tissue to normal levels
      of circulating hormones. CASE: Here, we report a female patient, aged 12 years
      and 6 months, suffering from juvenile breast hypertrophy, who presented at the
      third month of symptoms and benefited from tamoxifen treatment. COMMENTS: In
      experienced clinics, use of tamoxifen in the treatment of juvenile breast
      hypertrophy during the brisk growth period may become a medical alternative to
      reconstructive surgery.

PMID- 20813328
TI  - Unilateral non-communicating cervical atresia in a patient with uterus didelphys
      and unilateral renal agenesis.
AB  - A 16-year-old adolescent girl presented with chronic pelvic pain. Pelvic
      ultrasound and MRI showing a uterus didelphys, normal left uterus and cervix,
      right pelvic fluid collection and right unilateral renal agenesis. After two
      unsuccessful vaginal surgeries for drainage of hematotrachelos and creation of an
      outflow tract, patient underwent unilateral total abdominal hysterectomy with
      final pathology confirming hematotrachelos and non-communicating cervical atresia
      on the right. Patient on postoperative follow-up doing well.

PMID- 20813326
TI  - Cellular mechanisms of estradiol-mediated sexual differentiation of the brain.
AB  - Gonadal steroids organize the developing brain during a perinatal sensitive
      period and have enduring consequences for adult behavior. In male rodents
      testicular androgens are aromatized in neurons to estrogens and initiate multiple
      distinct cellular processes that ultimately determine the masculine phenotype.
      Within specific brain regions, overall cell number and dendritic morphology are
      the principal targets for hormonal organization. Recent advances have been made
      in elucidating the cellular mechanisms by which the neurological underpinnings of
      sexually dimorphic physiology and behavior are determined. These include
      estradiol-mediated prostaglandin synthesis, presynaptic release of glutamate,
      postsynaptic changes in glutamate receptors and changes in cell adhesion
      molecules. Sex differences in cell death are mediated by hormonal modulation of
      survival and death factors such as TNFalpha and Bcl-2/BAX.

PMID- 20813329
TI  - Neuroblastoma--the gynecologic perspective.

PMID- 20813330
TI  - Building capacity to implement cognitive pharmaceutical services: Quantifying the
      needs of community pharmacies.
AB  - BACKGROUND: Community pharmacy is an industry undergoing a transformation,
      evolving from a traditional product supply orientation to a business capable of
      incorporating services. The theoretical framework of organizational flexibility
      is used to understand how pharmacies' capacity can be built to provide services
      and identify key areas needing improvement. OBJECTIVE: To determine the needs of
      pharmacies that were important and the elements requiring improvement when
      implementing and delivering services. METHODS: A mail survey of 2006 Australian
      community pharmacies was used to identify needs for service implementation. A 25
      item scale was used to measure the level of importance (importance measure) of
      the items and the level of improvement (improvement measure) when implementing
      services. An exploratory factor analysis was conducted to assess the construct
      validity and reliability. RESULTS: Responses were received from a total of 395
      community pharmacies, with 355 usable responses (17.7%). Factor analysis yielded
      3 factors on the importance measure, explaining 42.6% of the variance: (1)
      planning and performance (item loading range 0.749-0.455; Cronbach's alpha
      0.806), (2) people and processes (0.829-0.392; 0.713), and (3) service awareness
      and infrastructure (0.723-0.310; 0.705). For the improvement measure, 46.9% of
      the variance was explained by 3 factors: (1) planning, performance, and service
      awareness (0.827-0.447; 0.858), (2) infrastructure (0.900-0.637; 0.822), and (3)
      people and processes (0.903-0.311; 0.707). CONCLUSIONS: The analyses showed that
      there are gaps in the capacity of community pharmacy that could be addressed
      through business and management programs. The theoretical framework of
      organizational flexibility was useful in highlighting the key areas for
      stimulating change. To effectively implement services and sustain service
      delivery, more sophisticated planning and performance monitoring systems are
      required, supported by changes to infrastructure and staff mix. The critical area
      for policy makers is the speed at which programs can be restructured to include
      these issues to encourage the widespread implementation of services.

PMID- 20813331
TI  - Problem prescriptions in Sweden necessitating contact with the prescriber before
      dispensing.
AB  - BACKGROUND: Pharmacists have an important role in detecting, preventing, and
      solving prescription problems, which if left unresolved, may pose a risk of
      harming the patient. OBJECTIVES: The aim was to examine prescription problems
      detected at pharmacies in Sweden, where pharmacists consider it necessary to
      contact the prescribers for clarification, completion or correction of the
      prescriptions before dispensing, and to compare the intervention rates at public
      pharmacies at hospitals (PPHs) with those at city center pharmacies (CCPs).
      METHODS: All attempts to contact the prescriber about a prescription problem were
      recorded by trained observers (pharmacy students). Analyses were made of overall
      distribution of problem prescriptions, including data from all 14 participating
      pharmacies, and a comparison between CCPs and PPHs with data from the 5 areas,
      each consisting of 1 CCP and 1 PPH (10 pharmacies). Chi-square-analyses were used
      to compare proportions, Spearman's rank-correlation coefficient was used to test
      correlation between recorded rates and dispensed volume, and Wilcoxon two-sample
      test was used to test differences between the CCPs and PPHs. P<.05 is regarded as
      statistically significant. RESULTS: The pharmacists contacted the prescribers for
      1% of all new prescriptions before dispensing. Errors that may compromise patient
      safety and medication outcome constituted almost 60% of the problems. However,
      there was an inverse correlation between the intervention rates and the
      pharmacy's dispensing volume. Significantly lower rates of problem prescriptions
      were recorded for women than for men. The highest rates were seen for
      prescriptions to patients younger than 15 years, and the rates decreased with
      increasing patient age. Pharmacists at PPHs contacted the prescribers about
      prescription problems twice as often as those at large CCPs. Pharmacists spent an
      average of 5 minutes on the telephone to solve the problem (median time), but 25%
      of the prescriptions took 10 minutes or more. CONCLUSIONS: Computerized physician
      order entry (CPOE) and electronically transmitted prescriptions (ETP) can not
      only reduce the total rate of prescription problems, but also introduce new
      clinically important errors that may compromise patient safety and medication
      outcome. The prescription problem rates in the present study differed across
      prescriber groups and patient age and gender, and the inverse correlation to
      pharmacy size indicates that all problems are not revealed and corrected and may
      thus reach the patient. CPOE and ETP have been used extensively in Sweden for the
      past decade, but the present study indicates that there is still a potential and
      need for improvement for the vision of "no prescribing errors/problems will reach
      the patient" to come true.

PMID- 20813332
TI  - Receiving a pharmaceutical care service compared to receiving standard pharmacy
      service in Sweden--How do patients differ with regard to perceptions of medicine
      use and the pharmacy encounter?
AB  - BACKGROUND: Qualitative research has shown that gaining control of medicine
      treatment and increased feelings of safety and empowerment are central concepts
      in patients' perceptions of a pharmaceutical care (PC) service provided in
      Sweden. However, little is known about any unique differences among patients
      receiving PC versus standard pharmacy services (SSs) and the impact of these
      services on patient-perceived outcomes. OBJECTIVE: To describe and compare
      patients who had previously received a PC service and patients who had received a
      SS with regard to their perceptions of medicine use and the pharmacy encounter.
      METHODS: Cross-sectional survey design comparing matched groups of patients who
      were previously elected to receive a PC service or who had received SS. Patients
      who were 60 years or older and used 5 or more prescription medicines
      concomitantly were included in the survey. Questionnaires included questions
      about perceptions of safety in drug therapy, general health, drug-related
      problems (DRPs), medication beliefs, adherence, and experiences of pharmacy
      encounters. RESULTS: Patients receiving the PC service used more prescription
      medicines, reported poorer self-reported health, and less perceived safety in
      their medicine therapy than did patients in SS. PC patients reported that they
      felt safer with medications, felt a genuine interest from the pharmacist,
      received important information, and felt more prepared to see the doctor after
      having spoken to the pharmacist than did patients in SS. DRPs reported to a
      greater extent by patients receiving the PC service included difficulties opening
      containers, worries about side effects, experiences of side effects, worries
      about drug-drug interactions, and inadequate treatment effects. Adherence and
      medication beliefs showed no statistical difference between groups. CONCLUSION:
      Patients receiving a PC service are a worried, vulnerable, and information
      seeking group. When compared with patients receiving SS, the PC patients are more
      insecure about their medicine therapy, although talking to a pharmacist increased
      their self-reported feelings of safety and provided better preparation for visits
      to the doctor.

PMID- 20813333
TI  - Use of complementary and alternative medicine for treatment among African
      Americans: a multivariate analysis.
AB  - BACKGROUND: The use of complementary and alternative medicine (CAM) is
      substantial among African-Americans; however, research on characteristics of
      African-Americans who use CAM to treat specific conditions is scarce. OBJECTIVE:
      To determine what predisposing, enabling, need, and disease-state factors are
      related to CAM use for treatment among a nationally representative sample of
      African-Americans. METHODS: A cross-sectional study design was employed using the
      2002 National Health Interview Survey (NHIS). A nationwide representative sample
      of adult (> or =18 years) African-Americans who used CAM in the past 12 months
      (n=16,113,651 weighted; n=2,952 unweighted) was included. The Andersen Health
      Care Utilization Model served as the framework with CAM use for treatment as the
      main outcome measure. Independent variables included the following: predisposing
      (eg, age, gender, and education); enabling (eg, income, employment, and access to
      care); need (eg, health status, physician visits, and prescription medication
      use); and disease state (ie, most prevalent conditions among African-Americans)
      factors. Multivariate logistic regression was used to address the study
      objective. RESULTS: Approximately 1 in 5 (20.2%) who used CAM in the past 12
      months used CAM to treat a specific condition. Ten of the 15 CAM modalities were
      used primarily for treatment by African-Americans. CAM for treatment was
      significantly (P<.05) associated with the following factors: graduate education,
      smaller family size, higher income, region (northeast, midwest, west more likely
      than south), depression/anxiety, more physician visits, less likely to engage in
      preventive care, more frequent exercise behavior, more activities of daily living
      (ADL) limitations, and neck pain. CONCLUSIONS: Twenty percent of African
      Americans who used CAM in the past year were treating a specific condition.
      Alternative medical systems, manipulative and body-based therapies, and folk
      medicine, prayer, biofeedback, and energy/Reiki were used most often. Health care
      professionals should routinely ask patients about the use of CAM, but when
      encountering African-Americans, there may be a number of factors that may serve
      as cues for further inquiry.

PMID- 20813334
TI  - Future economic outlook of Nebraska rural community pharmacies based on break
      even analysis of community operational costs and county population.
AB  - BACKGROUND: There is growing concern over increasingly limited access to local
      health care, including pharmacies, for rural citizens of the United States.
      Although geographically distant from most competitors, rural pharmacies may still
      struggle to generate an acceptable profit to remain economically viable.
      Therefore, a method for calculating the economic viability for a community
      pharmacy to recruit a potential new owner to assume the entrepreneurial risk is
      an important issue to consider when evaluating rural pharmacy access. OBJECTIVES:
      The primary objective of this study was to use a modified break-even analysis to
      predict the future financial potential of the current pharmacy business to
      attract a new owner. The secondary objective was to forecast a risk level for a
      Nebraska county to sustain the number of pharmacies in the country beyond current
      ownership. METHODS: This research used data provided by pharmacies that responded
      to a Nebraska Medicaid cost of dispensing (COD) survey in addition to data from
      the US Census Bureau, US Office of Management and Budget, and the Nebraska State
      Board of Pharmacy. Break-even analysis was used to determine the point where the
      prescription volume of the pharmacy not only covered the variable and fixed costs
      but also maintained a reasonable profit to attract new ownership. Counties were
      classified into 3 risk levels based on the projected available prescription
      volume and the number of pharmacies in each county. Sensitivity analysis was
      performed on the risk levels to determine the impact of variance in projected
      available prescription volume on the projected future outlook for the pharmacies
      in each county. RESULTS: Regression analysis of responses to the COD survey
      indicated that the annual break-even prescription volume ranged from 44,790 to
      49,246 prescriptions per pharmacy per annum. The number of rural Nebraska
      pharmacies was projected to decline from 126 to 78. The number of counties in
      Nebraska without a single pharmacy was projected to increase from 19 to 26, and
      the number of counties with just one pharmacy was projected to increase from 17
      to 31. Thus, the number of counties with 1 or no pharmacy was projected to
      increase to 57 out of the total 93 Nebraska counties. CONCLUSIONS: The forecasted
      closure of pharmacies in rural areas will cause significant portions of the state
      to be without a pharmacy. Low county populations will be unable to sustain a
      local prescription volume large enough to remove them from the high risk of
      pharmacy closure.

PMID- 20813335
TI  - Consumers' views of pharmacogenetics--A qualitative study.
AB  - BACKGROUND: Adverse drug reactions are recognized as a significant public health
      issue. Pharmacogenetics (PGx) provides a potential means of preventing some
      adverse drug reactions by predicting the optimal medication dose for an
      individual; however, PGx is rarely used in clinical practice. Thus far, there
      have been few studies investigating consumers' perceptions of the barriers to the
      implementation of PGx in clinical practice. OBJECTIVES: This study explored the
      views of the general public regarding their current use of medications, and their
      experiences of side effects and opinions on PGx. METHODS: Members of the general
      public who suffered a chronic medical condition and/or had an immediate family
      member with a chronic medical condition were recruited to form 5 separate focus
      groups (n=35). Three separate age ranges were used in the focus groups. A
      questioning route was developed and used in focus groups to determine
      participants' experiences with medication use and opinions on PGx (referred to as
      "Personalized Medicine"). Focus group discussions were transcribed by 2 separate
      investigators, and qualitative analysis, based on the framework approach, was
      applied to the data. Data were independently coded to identify key themes then
      compared both within and between focus groups. RESULTS: A common theme was a
      desire to have a holistic approach to disease diagnosis and medication selection.
      A wide range of views were expressed by the focus group participants. Concerns
      were raised regarding the current level of side effects experienced with
      medications. Storage and privacy of genetic information, and the costs involved,
      were also seen as potential barriers to implementation of PGx. CONCLUSIONS: PGx
      testing was seen as a potential positive contribution, but only if other factors
      were considered during the prescribing process. As participants desired a high
      level of information and effective communication from their health-care
      professionals, PGx education of clinicians and pharmacists will be essential to
      satisfy consumers' requirements.

PMID- 20813336
TI  - Factors related to pharmacists' care of migraineurs.
AB  - BACKGROUND: Migraine is a common, disabling, and underdiagnosed condition.
      Pharmacists are in an excellent position to help improve migraineur outcomes. The
      Pharmacists Care of Migraineurs Scale (PCMS) may be useful for documenting
      migraineur care and in the design and targeting of interventions aimed at
      improving care. OBJECTIVES: (1) To identify personal and situational work
      variables associated with pharmacists' provision of care to migraineurs that is
      measured using the PCMS; and (2) to determine which of these same variables are
      associated with each domain of care composing the PCMS. METHODS: The PCMS is a 41
      item measure eliciting pharmacists' frequencies of engagement in certain care
      behaviors comprising 7 unique domains. A survey questionnaire was mailed to a
      nationwide random sample of 6000 community pharmacists containing the PCMS and
      other items measuring personal and situational work variables. Factor scores of
      responses from a principal axis factoring procedure composing the PCMS were saved
      as dependent variables. Respondents' composite PCMS scores and each of the 7
      factor scores were regressed over the personal and situational work variables in
      8 unique stepwise regression procedures to identify those variables significant
      in explaining pharmacists' care of migraineurs. RESULTS: The 3 independent study
      variables most closely related to provision of care to migraineurs were self
      assessed knowledge of migraine, perceived difficulty (lack of), and caring
      ability. Models for individual PCMS domains were similar; however, some models
      included extroversion and pharmacy organizational culture variables, such as
      patient orientation and quality focus. CONCLUSIONS: Self-assessed knowledge of
      migraine, perceived lack of difficulty, and caring ability are important
      determinants in the level of care provided to migraineurs by pharmacists. Future
      study should further delineate the role of the pharmacy's work environment and
      pharmacists' training needs in elevating levels of care. Comprehensive continuing
      education programs on migraine management would appear advisable.

PMID- 20813337
TI  - Full costs of dispensing and administering fluorouracil chemotherapy for
      outpatients: A microcosting study.
AB  - BACKGROUND: Although full costs (including direct and indirect costs) that
      incurred during the process of chemotherapy administration should be measured,
      many studies estimate only direct labor and medication costs associated with
      various chemotherapy delivery systems. OBJECTIVES: To estimate the total costs
      for dispensing and administration of fluorouracil when administered with
      leucovorin, by intravenous infusion or bolus, using a microcosting approach from
      the perspective of a provider or health system. METHODS: A time-and-motion study
      was used to measure the time spent by (1) pharmacy staff in the handling,
      admixture, and dispensing of fluorouracil and (2) patients in the clinic. The
      study was performed at The Cancer Institute of New Jersey for an 8-month period.
      Costs of dispensing and administering fluorouracil were calculated per patient
      visit on the basis of resources used in the processing of fluorouracil and time
      spent by pharmacy staff and patient. All costs were standardized to 2005 dollars.
      RESULTS: A total of 275 observations were made, and 74 (26.9%) of these were
      associated with fluorouracil-based chemotherapy. Pharmacy staff spent an average
      of 11 minutes for bolus fluorouracil with leucovorin infusion (fluorouracil/LCV
      IV) and 8 minutes for bolus fluorouracil with bolus leucovorin (fluorouracil/LCV
      B). Patients who received fluorouracil/LCV-IV spent an average of 203 minutes in
      the clinic, whereas patients who received fluorouracil/LCV-B spent 110 minutes.
      The average cost of administering fluorouracil/LCV-IV was $933, which comprised
      drug costs ($279), dispensing costs ($189), and administration costs ($465). The
      average cost of fluorouracil/LCV-B was $474, which comprised drug costs ($65),
      dispensing costs ($141), and administration costs ($268). CONCLUSIONS: This is
      the first study to formally demonstrate the high cost of administering the
      injectable form of fluorouracil chemotherapy with leucovorin, despite relatively
      low drug acquisition cost. Therefore, reimbursement rates for fluorouracil should
      be calculated in such a way that covers all costs, including overhead costs for
      the department.

PMID- 20813338
TI  - Identifying early prescribers of cycloxygenase-2 inhibitors (COX-2s) in Nova
      Scotia, Canada: Considerations for targeted academic detailing.
AB  - BACKGROUND: Expenditures on prescribed drugs in Canada are now well past those
      for all services provided by outpatient physicians ($26.9 billion vs. $21.5
      billion in 2007). Government has the opportunity to dedicate resources to
      continuing medical education of physicians, and effective profiling would assist
      in the allocation of these educational resources. OBJECTIVE: The purpose of this
      study was to evaluate physician prescribing patterns and establish criteria by
      which various prescribing profiles may be segmented and identified, so as to
      better target detailing and continuing medical education resources. METHODS: A
      sample of 925 physicians practicing in Nova Scotia (NS) was characterized by age,
      sex, rural/urban nature of their practice and specialty. They were subsequently
      evaluated relative to all prescriptions filled by their patients who were
      beneficiaries of the NS Department of Health's senior's Pharmacare drug insurance
      program. The adoption of COX-2 inhibitors (eg, Vioxx) and Celebrex) and their
      substitution for NS-NSAIDs (non-specific non-steroidal anti-inflammatory drugs,
      eg, Motrin) from 1999 to 2003 were examined. RESULTS: This analysis established
      the profiles of 2 key groups of physicians. The first consisted of those most
      likely to comprise the early, high volume COX-2-prescribing universe (profiles
      based on the absolute number of prescriptions written over a given period). These
      individuals were likely to be older, more experienced, male general practitioners
      operating in a rural practice. The second group consisted of those most likely to
      comprise the early, high-relative, COX-2-prescribing universe (prescribing of COX
      2s relative to non-selective, non-steroidal anti-inflammatory drugs (NS-NSAIDs)).
      These individuals were likely to be younger, less experienced female general
      practitioners, operating in an urban practice. CONCLUSION: This research moves us
      closer to identifying unique physician segments that account for either the
      largest volume of prescriptions for new drugs, or the largest relative volume of
      prescriptions. Use of these physician groups can help continuing medical
      education providers target specific prescribers with information to assist them
      in examining and improving their prescribing.

PMID- 20813339
TI  - Requiring an amyloid-beta1-42 biomarker for prodromal Alzheimer's disease or mild
      cognitive impairment does not lead to more efficient clinical trials.
AB  - BACKGROUND: Low cerebrospinal fluid (CSF) amyloid-beta(1-42) concentration and
      high total-tau/Abeta(1-42) ratio have been recommended to support the diagnosis
      of prodromal Alzheimer's disease (AD) in patients with amnestic mild cognitive
      impairment (aMCI) and also to select patients for clinical trials (Shaw et al,
      Ann Neurol 2009;65:403-13; Dubois et al, Lancet Neurol 2007;6:734-46). METHODS:
      We tested this recommendation with clinical trials simulations using patients
      from the Alzheimer Disease Neuroimaging Initiative who fulfilled the following
      entry criteria: (1) aMCI, (2) aMCI with CSF Abeta(1-42) <or=192 mg/mL, (3) and
      aMCI with total-tau/Abeta(1-42) >0.39. For each criterion, we randomly resampled
      the database obtaining samples for 1000 trials for each trial scenario, planning
      for 1 or 2 year trials with samples from 50 to 400 patients per treatment or
      placebo group, with up to 40% dropouts, outcomes after using the AD assessment
      scale-cognitive subscale and clinical dementia rating scale with effect sizes
      ranging from 0.15 to 0.75, and calculated statistical power. FINDINGS:
      Approximately 70% to 74% of aMCI patients with CSF measures met biomarker
      criteria. The addition of the low Abeta(1-42) or high tau/Abeta(1-42) requirement
      resulted in minimal or no increase in the power of the trials compared with
      enrolling aMCI without requiring the biomarker criteria. Slightly larger mean
      differences between the placebo and treatment groups fulfilling biomarker
      criteria were offset by increased outcome variability within the groups.
      INTERPRETATIONS: Although patients with aMCI or patients with prodromal AD
      meeting CSF biomarkers criteria were slightly more cognitively impaired and
      showed greater decline than patients with aMCI diagnosed without considering the
      biomarkers, the requirement of biomarker-positive patients would most likely not
      result in more efficient clinical trials, and trials would take longer because
      fewer patients would be available. A CSF Abeta(1-42) marker, however, could be
      useful as an explanatory variable or covariate when warranted by the action of a
      drug.

PMID- 20813340
TI  - Plasma ceramides are altered in mild cognitive impairment and predict cognitive
      decline and hippocampal volume loss.
AB  - BACKGROUND: A blood-based biomarker of Alzheimer's disease (AD) would be superior
      to cerebrospinal fluid (CSF) and neuroimaging measures in terms of cost,
      invasiveness, and feasibility for repeated measures. We previously reported that
      blood ceramides varied in relation to timing of memory impairment in a population
      based study. The present objective was to examine whether plasma ceramides varied
      by AD severity in a well-characterized clinic sample and were associated with
      cognitive decline and hippocampal volume loss over 1 year. METHODS: Participants
      included 25 normal controls (NC), 17 amnestic Mild Cognitive Impairment (MCI),
      and 21 early probable AD. A thorough neuropsychological battery and neuroimaging
      with hippocampal volume determination were conducted at baseline and 1 year
      later. Plasma ceramides were assayed at baseline using high performance liquid
      chromatography coupled electrospray ionization tandem mass spectrometry. RESULTS:
      Although all saturated ceramides were lower in MCI compared with AD at baseline,
      ceramides C22:0 and C24:0 were significantly lower in the MCI group compared with
      both NC and AD groups (P < .01). Ceramide levels did not differ (P > .05) in AD
      versus NC. There were no cross-sectional associations between ceramides C22:0 and
      C24:0 and either cognitive performance or hippocampal volume among any group.
      However, among the MCI group, higher baseline ceramide C22:0 and C24:0 levels
      were predictive of cognitive decline and hippocampal volume loss 1 year later.
      CONCLUSION: Results suggest that very long-chain plasma ceramides C22:0 and C24:0
      are altered in MCI and predict memory loss and right hippocampal volume loss
      among subjects with MCI. These plasma ceramides may be early indicators of AD
      progression.

PMID- 20813341
TI  - Cerebral atrophy, apolipoprotein E varepsilon4, and rate of decline in everyday
      function among patients with amnestic mild cognitive impairment.
AB  - BACKGROUND: Patients with amnestic mild cognitive impairment (MCI) demonstrate
      decline in everyday function. In this study, we investigated whether whole brain
      atrophy and apolipoprotein E (APOE) genotype are associated with the rate of
      functional decline in MCI. METHODS: Participants were 164 healthy controls, 258
      MCI patients, and 103 patients with mild Alzheimer's disease (AD), enrolled in
      the Alzheimer's Disease Neuroimaging Initiative. They underwent brain MRI scans,
      APOE genotyping, and completed up to six biannual Functional Activities
      Questionnaire (FAQ) assessments. Random effects regressions were used to examine
      trajectories of decline in FAQ across diagnostic groups, and to test the effects
      of ventricle-to-brain ratio (VBR) and APOE genotype on FAQ decline among MCI
      patients. RESULTS: Rate of decline in FAQ among MCI patients was intermediate
      between that of controls and mild AD patients. Patients with MCI who converted to
      mild AD declined faster than those who remained stable. Among MCI patients,
      increased VBR and possession of any APOE varepsilon4 allele were associated with
      faster rate of decline in FAQ. In addition, there was a significant VBR by APOE
      varepsilon4 interaction such that patients who were APOE varepsilon4 positive and
      had increased atrophy experienced the fastest decline in FAQ. CONCLUSIONS:
      Functional decline occurs in MCI, particularly among patients who progress to
      mild AD. Brain atrophy and APOE varepsilon4 positivity are associated with such
      declines, and patients who have elevated brain atrophy and are APOE varepsilon4
      positive are at greatest risk of functional degradation. These findings highlight
      the value of genetic and volumetric MRI information as predictors of functional
      decline, and thus disease progression, in MCI.

PMID- 20813342
TI  - Influence of apolipoprotein E varepsilon4 on rates of cognitive and functional
      decline in mild cognitive impairment.
AB  - BACKGROUND: Apolipoprotein E varepsilon4 (APOE varepsilon4) allele carrier status
      has been well established as a risk factor for developing Alzheimer's disease.
      However, the specific influence of APOE varepsilon4 allele status on cognitive
      and functional rates of decline in mild cognitive impairment (MCI) is poorly
      understood. We examine the prospective association of APOE varepsilon4 allele
      status on measures of cognitive and functional decline in subjects with amnestic
      MCI (aMCI). METHODS: A total of 516 aMCI participants aged 55-90 years who
      received placebo or vitamin E from the Alzheimer's Disease Cooperative Study's
      MCI treatment trial were evaluated. During the 36-month study period,
      neurocognitive and functional measures were collected. These measures were
      assessed over time for change and association with APOE varepsilon4 status.
      Generalized Estimating Equations were performed to model each outcome measure
      over the study period. RESULTS: APOE varepsilon4 status had a significant impact
      on cognitive and functional decline on multiple measures; those who were APOE
      varepsilon4 positive had significantly more rapid decline in performance on all
      cognitive and functional measures except Number Cancellation and Maze tracing (P
      < .05). The greatest decline was seen in global measures of cognition and
      function including the Clinical Diagnostic Rating scale, followed by the Mini
      Mental State Examination, Global Deterioration scale, and the Alzheimer's Disease
      Assessment Scale-Cognitive Subscale. CONCLUSIONS: These findings demonstrate that
      APOE varepsilon4 genotype is predictive of increased general rates of decline
      with global measures of cognition and function most affected. With accelerated
      declines in common clinical trial primary efficacy measures, APOE varepsilon4
      status needs to be accounted for in treatment trials of MCI.

PMID- 20813343
TI  - Alzheimer's disease, a multifactorial disorder seeking multitherapies.
AB  - Alzheimer's disease (AD) is multifactorial and apparently involves several
      different etiopathogenic mechanisms. There are at least five subgroups of AD
      based on cerebrospinal fluid levels of Abeta(1-42), a marker of beta-amyloid
      (Abeta) plaques, and tau and ubiquitin, two markers of neurofibrillary tangles.
      These different AD subgroups may respond differently to a given disease-modifying
      drug, and hence, different therapeutic drugs for different disease subgroups
      might be required. Stratification of AD patients by disease subgroups in clinical
      trials is critical to the successful development of potent disease-modifying
      drugs. Levels of disease markers in the cerebrospinal fluid are promising, both
      in identifying various subgroups of AD and in monitoring the response to
      therapeutic drugs.

PMID- 20813344
TI  - Current status of ceramic-based membranes for oxygen separation from air.
AB  - There has been tremendous progress in membrane technology for gas separation, in
      particular oxygen separation from air in the last 20 years. It provides an
      alternative route to the existing conventional separation processes such as
      cryogenic distillation and pressure swing adsorption as well as cheaper
      production of oxygen with high purity. This review presents the recent advances
      of ceramic membranes for the separation of oxygen from air at high temperature.
      It covers the issues and problems with respect to the selectivity and separation
      performance. The paper also presents different approaches applied to overcome
      these challenges. The future directions of ceramic-based membranes for oxygen
      separation from air are also presented.

PMID- 20813345
TI  - Spontaneous reattachment of Descemet stripping automated endothelial keratoplasty
      lenticles: a case series of 12 patients.
AB  - PURPOSE: To review 12 cases of postoperative detachment and spontaneous
      reattachment of Descemet stripping automated endothelial keratoplasty (DSAEK)
      lenticles. DESIGN: Retrospective, observational case series. METHODS: This was a
      review of patients undergoing DSAEK at 7 institutions. Patients who had a
      significant detachment of their DSAEK lenticle during the postoperative period
      were identified and divided into 2 groups. Significant detachment was defined as
      either complete central interface fluid with bare peripheral attachment (group 1)
      or a free-floating lenticle in the anterior chamber (group 2). Patients who
      subsequently had a spontaneous reattachment of the lenticle were identified, with
      data regarding surgical technique and intraoperative and postoperative
      complications collected for analysis. RESULTS: Our cohort consisted of 12 eyes of
      12 patients who met the definition of significant postoperative detachment with
      subsequent spontaneous reattachment. Four patients had complete central
      detachment with peripheral attachment (group 1), whereas 8 patients had a free
      floating lenticle (group 2). Ten of the 12 patients had a successful outcome as
      defined as an attached and clear DSAEK lenticle. In our study, reattachment was
      seen as early as 5 days and as late as 7 months after surgery, with reattachment
      in 9 of 12 patients by day 25. CONCLUSIONS: Spontaneous reattachment of detached
      DSAEK lenticles may occur during the postoperative period. The decision of when
      to bring the patient back for a rebubble ultimately must be made on a case-by
      case basis.

PMID- 20813346
TI  - Pharmacokinetics of azithromycin and moxifloxacin in human conjunctiva and
      aqueous humor during and after the approved dosing regimens.
AB  - PURPOSE: To evaluate the ocular pharmacokinetics of azithromycin and moxifloxacin
      in human conjunctiva and aqueous humor in subjects undergoing cataract surgery.
      DESIGN: Multicenter, open-label, randomized study. METHODS: Subjects scheduled
      for routine cataract surgery and with normal-appearing conjunctiva were eligible.
      One conjunctival biopsy sample and 1 aqueous humor sample were obtained from
      subjects randomly assigned to 1 of 10 prespecified time points (1 to 312 hours)
      after treatment initiation of azithromycin ophthalmic solution 1% or moxifloxacin
      ophthalmic solution 0.5%. Samples were assayed using liquid chromatography tandem
      mass spectrometry. RESULTS: Azithromycin 1% provided high concentrations (peak
      level, 559.7 MUg/g) in human conjunctiva that were sustained at levels 1 to 2
      orders of magnitude higher than those of moxifloxacin 0.5% throughout the 7-day
      dosing period and for at least 7 days thereafter. Azithromycin also showed an
      extended half-life (65.7 hours) in conjunctiva relative to that of moxifloxacin
      (28.6 hours). Accordingly, the concentration of azithromycin was maintained well
      above the minimum inhibitory concentration required for inhibition of growth of
      90% of tested bacterial isolates for at least 7 days, whereas moxifloxacin
      conjunctival levels fell to levels at or less than the minimum inhibitory
      concentration required for inhibition of growth of 90% of tested bacterial
      isolates approximately 24 hours after the last dose. Peak aqueous humor
      concentration of moxifloxacin was higher (0.77 MUg/mL) than that of azithromycin
      (0.053 MUg/mL). No clinically relevant safety findings were observed.
      CONCLUSIONS: Azithromycin 1% demonstrated high, therapeutic levels in the
      conjunctiva that were maintained up to 7 days after completion of a 1-week dosing
      regimen. Aqueous humor levels, however, were subtherapeutic with this dosing
      regimen. In comparison, moxifloxacin achieved lower conjunctival tissue levels,
      but higher aqueous humor levels.

PMID- 20813347
TI  - An ergonomic evaluation of infant life jackets: Donning time & donning accuracy.
AB  - Canada is considering the development of a new standard for infant/child life
      jackets. Eight currently available (approved and non-approved) infant/child life
      jackets were procured for evaluation. Fifty-six participants were chosen as a
      sample of convenience from the general public for testing. The life jackets were
      divided into two groups of four, which were donned on a soft infant manikin
      procured from the Red Cross. In 224 attempts at donning, only 43 (19%) attempts
      resulted in the life jacket being donned correctly in less than 1 min. Only one
      life jacket came close to a good design and passed the life jacket standard for
      donning time and accuracy. Failure rates were observed across all the
      participants irrespective of age, gender, experience with children and experience
      with recreational marine equipment. Accuracy and speed of donning the life jacket
      were hampered as the number of donning sub-tasks increased. It was concluded that
      it is possible to design a life jacket that can be donned correctly in under 1
      min. The life jacket must be of simple, intuitive design and fall naturally into
      the anatomical shape of the child. A minimum number of ties, zips and clips
      should be used in the design, and if such connectors are used they should be
      color coded or of different shapes and sizes to avoid confusion.

PMID- 20813348
TI  - Expression, localisation and synthesis of versican by the enamel organ of
      developing mouse molar tooth germ: an in vivo and in vitro study.
AB  - OBJECTIVE: Versican is a large, aggregating chondroitin sulphate proteoglycan. In
      dental tissue, versican expression occurs primarily in mesenchymal tissue but
      rarely in epithelial tissue. We investigated the expression, localisation and
      synthesis of versican in the enamel organ of the developing tooth germ. DESIGN:
      To elucidate versican localisation in vivo, in situ hybridisation and
      immunohistochemistry were conducted in foetal ICR mice at E11.5-E18.5. Epithelium
      and mesenchyme from the lower first molars at E16.0 were enzymatically separated
      and versican mRNA expression was investigated by semi-quantitative RT-PCR. Organ
      culture of the separated samples combined with metabolic labelling with [(35)S],
      followed by gel filtration, was performed to analyse secreted proteoglycans.
      RESULTS: Versican mRNA was first expressed in the thickened dental epithelium at
      E12.0 and continued to be expressed in the enamel organ until the bell stage.
      Versican immunostaining was detected in the stellate reticulum areas from the bud
      stage to the apposition stage. The enamel organ at E16.0 expressed versican mRNA
      at a level comparable to that in dental mesenchyme. Furthermore, when compared to
      dental mesenchyme, about 1/2-3/4 of the [(35)S]-labelled versican-like large
      proteoglycan was synthesised and released into tissue explants by the enamel
      organ. CONCLUSIONS: The dental epithelium of developing tooth germ is able to
      synthesise significant amounts of versican.

PMID- 20813349
TI  - Effect of rinsing with water immediately after neutral gel and foam fluoride
      topical application on enamel remineralization: An in situ study.
AB  - OBJECTIVE: The aim of this study was to evaluate, in situ, the effect of rinsing
      with water immediately after neutral fluoride foam application (Foam) or fluoride
      gel application (Gel). DESIGN: Ten volunteers wore acrylic palatal appliances
      containing 4 enamel blocks selected by surface hardness with artificial caries.
      Five experimental regimes of 3 days each were set according to treatment:
      placebo; Gel and Foam followed by no rinsing or consuming of liquids or solids
      for the next 30min; Gel and Foam followed by immediately washing with water jet.
      After each phase, surface hardness was again measured for analysis of mineral
      gain, evaluated through percentage of surface hardness recovery (%SHR) and
      integrated loss of subsurface hardness (DeltaKHN). The concentration of loosely
      bound fluoride (CaF2) and firmly bound fluoride (FA-like) formed and retained
      were also determined. RESULTS: Fluoride treatments produced greater
      remineralization (%SHR and DeltaKHN) compared to placebo group (p<0.05). There
      was no difference in the ability to promote remineralization and in the
      concentration of fluoride formed and retained, in each analysis, between Gel and
      Foam (p>0.05). CONCLUSION: The data suggest that rinsing with water immediately
      after topical application does not seem to have an influence on the ability of
      fluoride to promote remineralization.

PMID- 20813350
TI  - An evaluation of the effectiveness of diploma-level training in cognitive
      behaviour therapy.
AB  - BACKGROUND: As part of the UK government's initiative to Increase Access to
      Psychological Therapies (see http://www.iapt.nhs.uk/for full details of the IAPT
      programme) there has been an expansion in the provision of post-graduate Diploma
      training in cognitive behaviour therapy (CBT). Previous evaluations of such
      training programmes have yielded mixed results but have been limited by small
      sample sizes and/or limited assessment measures. AIMS: To evaluate the impact of
      a long-standing Diploma in CBT training programme on a variety of measures of CBT
      competence. METHOD: Trainees' levels of CBT skill are compared at the beginning
      and end of CBT training. The effect of therapist factors such as age,
      professional background and gender on the development of CBT competence is also
      examined. RESULTS: Results show that trainees demonstrate higher levels of CBT
      skills after completing the training than they did before, with the majority
      achieving pre-determined criteria for competence. Trainees' gender was not
      related to their performance but trainees' age showed a negative association with
      CBT skill (older trainees performed worse). Trainees' professional background
      also had an impact on their level of CBT competence, with trainees who were
      clinical psychologists demonstrating the highest levels of competence across a
      range of measures. CONCLUSIONS: CBT Diploma training leads to increases in the
      level of trainees' CBT competence, with the majority achieving the levels
      demonstrated in research trials by the end of training. Thus, this training is
      likely to lead to improved outcomes for patients. Further research is needed to
      determine the most efficient ways of enhancing CBT skills.

PMID- 20813351
TI  - Structural analysis of a highly sulfated fucan from the brown alga Laminaria
      cichorioides by tandem MALDI and ESI mass spectrometry.
AB  - Water-soluble polysaccharide fractions were extracted from the brown alga
      Laminaria cichorioides. Samples were collected monthly from May to October in
      Troitsa Bay (Japan Sea, Russia). Analysis showed that the content and
      monosaccharide composition of the fractions changed with the collection season.
      Fucoidan was isolated and purified from the most fucose-rich fraction, collected
      in July, and subjected to autohydrolysis to obtain fucooligosaccharides, suitable
      for mass-spectrometric analysis. Both ESIMS and MALDI-TOFMS analyses show that
      multisulfated (up to 3) fucooligosaccharides with polymerization degree n from 2
      to 5, including mono- and disulfated-fucose residues, were the major products of
      autohydrolysis. The structural features of the fucooligosaccharides and their
      alditol derivatives were elucidated by tandem MALDI-TOFMS and ESIMS. The results
      obtained allowed us to conclude that fragments of the fucoidan, collected in
      July, were predominantly linked with a (1->3)-type of linkage and that sulfate
      groups occupied mostly C-2 or C-2/C-4 of the alpha-l-fucose residues.

PMID- 20813352
TI  - Synthesis of the glycosaminoglycan-protein linkage tetraosyl peptide moieties of
      betaglycan, which serve as a hexosamine acceptor for enzymatic glycosyl transfer.
AB  - Betaglycan, also known as TGF-beta type III receptor, is a membrane-anchored
      proteoglycan, which has two glycosaminoglycan (GAG) attachment sites (Lopez
      Casillas, F.; Payne, H. M.; Andres, J. L.; Massague, J. J.Cell Biol.1994, 124,
      557-568). Chondroitin sulfate (CS) or heparan sulfate (HS) can attach to the
      first site, Ser(535), whereas only CS attaches to the second, Ser(546). Although
      the mechanism behind the assembly of CS and HS is not fully understood, it has
      been reported that the assembly of HS requires not only a cluster of acidic
      residues but also hydrophobic residues located near the Ser-Gly attachment sites
      (Esko, J. D. Zhang, L. Curr. Opin. Struct. Biol.1996, 6, 663-670). To further
      understand the effects of amino acids close to the Ser residues of the GAG
      attachment sites on the glycosyltransferases, two tetraosyl peptides derived from
      the CS attachment sites of betaglycan, GlcA-Gal-Gal-Xyl-SerGlyAspAsnGly (1) and
      GlcA-Gal-Gal-Xyl-SerGlyAspAsnGlyPheProGly (2), were synthesized, and used as
      donor substrates for beta1,4-N-acetylgalactosaminyltransferase-I (beta4GalNAcT-I)
      and alpha1,4-N-acetylglucosaminyltransferase-I (alpha4GlcNAcT-I). Both the
      chemically synthesized linkage region tetrasaccharides were far better acceptors
      for beta4GalNAcT-I than for alpha4GlcNAcT-I in vitro, although they also showed
      appreciable acceptor activity for alpha4GlcNAcT-I.

PMID- 20813353
TI  - [Major ambulatory surgery and clinical pathways: a stimulating combination].
AB  - The success of major ambulatory surgery (MAS) in Spain is due to the need to
      shorten the surgical waiting list for procedures of low to medium complexity, and
      the efficiency, satisfaction and safety that it can obtain. Clinical Pathways
      (CP) are defined health care plans, supported by scientific evidence, prepared
      for specific environments, on "Clinical Processes" with, a predictable clinical
      course, high prevalence and variability. The sequence of all the activities are
      set out in detail in them, as well as checking the performance of the
      professionals involved. MAS is performed using strict protocols and coordination
      between different specialties and health care levels. If CPs have demonstrated
      their usefulness in elective surgery, it could be assumed that the contribution
      of CPs could be equally applied to MAS procedures. In this article, we review the
      methodology for introducing CP into MAS, as well as its obstacles and
      expectations.

PMID- 20813354
TI  - [Peritoneal tuberculosis as a cause of ascites of unknown origin].

PMID- 20813355
TI  - Enough skill to kill: intentionality judgments and the moral valence of action.
AB  - Extant models of moral judgment assume that an action's intentionality precedes
      assignments of blame. Knobe (2003b) challenged this fundamental order and
      proposed instead that the badness or blameworthiness of an action directs (and
      thus unduly biases) people's intentionality judgments. His and other researchers'
      studies suggested that blameworthy actions are considered intentional even when
      the agent lacks skill (e.g., killing somebody with a lucky shot) whereas
      equivalent neutral actions are not (e.g., luckily hitting a bull's-eye). The
      present five studies offer an alternative account of these provocative findings.
      We suggest that people see the morally significant action examined in previous
      studies (killing) as accomplished by a basic action (pressing the trigger) for
      which an unskilled agent still has sufficient skill. Studies 1 through 3 show
      that when this basic action is performed unskillfully or is absent, people are
      far less likely to view the killing as intentional, demonstrating that
      intentionality judgments, even about immoral actions, are guided by skill
      information. Studies 4 and 5 further show that a neutral action such as hitting
      the bull's-eye is more difficult than killing and that difficult actions are less
      often judged intentional. When difficulty is held constant, people's
      intentionality judgments are fully responsive to skill information regardless of
      moral valence. The present studies thus speak against the hypothesis of a moral
      evaluation bias in intentionality judgments and instead document people's
      sensitivity to subtle features of human action.

PMID- 20813356
TI  - Can false memories prime problem solutions?
AB  - Previous research has suggested that false memories can prime performance on
      related implicit and explicit memory tasks. The present research examined whether
      false memories can also be used to prime higher order cognitive processes,
      namely, insight-based problem solving. Participants were asked to solve a number
      of compound remote associate task (CRAT) problems, half of which had been primed
      by the presentation of Deese/Roediger-McDermott (DRM) lists whose critical lure
      was also the solution to the problem. The results showed that when the critical
      lure: (a) was falsely recalled, CRAT problems were solved more often and
      significantly faster than problems that were not primed by a DRM list and (b) was
      not falsely recalled, CRAT problem solution rates and times were no different
      than when there was no DRM priming. A second experiment demonstrated that these
      outcomes were not a simple artifact of the inclusion of a recall test prior to
      the problem solving task. The implications of these results are discussed with
      regard to the previous literature on priming and the adaptive function of false
      memories.

PMID- 20813357
TI  - Day 2 versus day 3 embryo transfer in poor responders: a prospective randomized
      trial.
AB  - Day 2 embryo transfer has been suggested as a method to improve pregnancy rates
      in poor responders compared with day 3 transfer. Our prospective randomized
      controlled trial does not show a difference in outcomes based on day of embryo
      transfer.

PMID- 20813358
TI  - International Federation of Fertility Societies Surveillance 2010: preface.
AB  - Surveillance is a triennial worldwide compendium of national rules and
      regulations for assisted reproductive technology. It was last published in 2007.

PMID- 20813359
TI  - Perinatal outcome of singleton siblings born after assisted reproductive
      technology and spontaneous conception: Danish national sibling-cohort study.
AB  - OBJECTIVE: To compare the perinatal outcome of singleton siblings conceived
      differently. DESIGN: National population-based registry study. SETTING: Denmark,
      from 1994 to 2008. PATIENT(S): Pairs of siblings (13,692 pairs; n = 27,384
      children) conceived after IVF, intracytoplasmatic sperm injection (ICSI), frozen
      embryo replacement (FER), or spontaneous conception subcategorized into five
      groups according to succession: [1] IVF-ICSI vs. spontaneous conception (n =
      7,758), [2] IVF-ICSI vs. FER (n = 716), [3] FER vs. FER (n = 34), [4] IVF-ICSI
      vs. IVF-ICSI (n = 2,876), and [5] spontaneous conception vs. spontaneous
      conception (n = 16,000). INTERVENTION(S): Observations were obtained from
      national registries. MAIN OUTCOME MEASURE(S): Birth weight, gestational age, low
      birth weight (<2,500 g), preterm birth (<37 weeks' gestation) and perinatal
      deaths. RESULT(S): Mean birth weight was 65 g (95% confidence interval [CI], 41
      89] lower in all assisted reproductive technology children compared with their
      spontaneously conceived siblings. FER children were 167 g (95% CI, 90-244]
      heavier than siblings born after replacement of fresh embryos. The difference in
      birth weight between firstborn and second born sibling depended on order of
      conception method. Higher risk of low birth weight with (odds ratio [OR], 1.4;
      95%CI, 1.1-1.7] and preterm birth (OR, 1.3; 95% CI, 1.1-1.6] was observed in
      IVF/ICSI compared with spontaneous conception. CONCLUSION(S): When
      differentiating between order and mode of conception, it seems that assisted
      reproductive technology plays a role in mean birth weight and risk of low birth
      weight and preterm birth. Birth weight was higher in siblings born after FER
      compared with fresh embryos replacement.

PMID- 20813360
TI  - Peroxisome proliferator-activated receptor gamma and early folliculogenesis
      during an acute hyperandrogenism condition.
AB  - Acute hyperandrogenism decreases serum P levels and induces early apoptosis of
      antral follicles by a mechanism mediated by the peroxisome proliferator-activated
      receptor gamma system and independent of the steroidogenic acute regulator
      protein.

PMID- 20813361
TI  - Hemorheologic profile in healthy women undergoing controlled ovarian stimulation.
AB  - We investigated the hemorheologic profile in 110 women undergoing controlled
      ovarian stimulation and provide evidence that smokers and women with body mass
      index>25 kg/m2 exhibit alterations of rheologic profile. A progressive increase
      of whole-blood viscosity throughout the ovarian stimulation cycle was observed;
      deformability and aggregation of erythrocytes decreased from baseline to the
      beginning of recombinant FSH administration, then remained unchanged throughout
      the next days; hematocrit mildly decreased during the last days of recombinant
      FSH administration; and fibrinogen and cholesterol levels decreased and
      increased, respectively, throughout the stimulation cycle.

PMID- 20813362
TI  - Benefit of uterine artery ligation in laparoscopic myomectomy.
AB  - OBJECTIVE: To determine the impact of uterine artery ligation in laparoscopic
      myomectomy, according to surgical results and clinical outcomes. DESIGN: Single
      center, nonrandomized, comparative study. SETTING: University hospital, tertiary
      referral center. PATIENT(S): Ninety women undergoing laparoscopic myomectomy.
      INTERVENTION(S): Laparoscopic myomectomy with or without uterine artery ligation.
      MAIN OUTCOME MEASURE(S): Surgical results and clinical outcomes. RESULT(S): Fifty
      one patients (56.6%) underwent laparoscopic myomectomy with uterine artery
      ligation (group A), and 39 patients (43.3%) underwent laparoscopic myomectomy
      alone (group B). The mean operating time was 100.0 +/- 33.8 minutes in group A
      and 90.0 +/- 37.1 minutes in group B. Both groups were similar with respect to
      mean blood loss (72.3 +/- 109.0 mL vs. 62.6 +/- 77.3 mL). The myoma recurrence
      rate in group A was significantly less than in group B after a median follow-up
      period of 11.1 months (2% vs. 13%). CONCLUSION(S): Both groups were similar with
      respect to surgical results. However, the recurrence rate was significantly lower
      in group A compared with group B.

PMID- 20813363
TI  - Microdose gonadotropin-releasing hormone agonist in the absence of exogenous
      gonadotropins is not sufficient to induce multiple follicle development.
AB  - Because the effectiveness of the "microdose flare" stimulation protocol often is
      attributed to the dramatic endogenous gonadotropin release induced by the GnRH
      agonist, the aim of this study was to determine whether use of microdose GnRH
      agonist alone could induce multiple ovarian follicle development in normal
      responders. Based on these data, the duration of gonadotropin rise is
      approximately 24 to 48 hours and is too brief to sustain continued multiple
      follicle growth.

PMID- 20813364
TI  - Study of dental caries and periapical lesions in a mediaeval population of the
      southwest France: differences in visual and radiographic inspections.
AB  - Dental caries and periapical lesions have often been studied in archaeological
      samples. The majority of these studies concern lesions detected clinically and,
      in some cases, radiography is used to improve the scoring results. The purpose of
      the present study was to compare and combine the two methods for recording caries
      and cysts. The studied dental material derived from a mediaeval sample from the
      south of France. The study included sixty mandibles (788 teeth). Each tooth was
      observed clinically and radiographically. Absence of teeth was noted and
      unerupted teeth, which could be viewed on radiographs were also noted. The
      location and degree of development of each lesion were recorded. Occlusal lesions
      of degree 1 were mostly detected clinically (5.1% vs.1.4% detected
      radiographically). Radiographic detection increased the score of approximal
      lesions of degree 2 (1.4% vs. 0.7%) and the detection of intraosseous lesions.
      This research has shown that the combination of radiographic and clinical
      examinations improves the caries detection and thus, increases the caries score
      in a studied dental sample.

PMID- 20813365
TI  - Association of birth weight and length with air temperature, sunlight, humidity
      and rainfall in the city of Warsaw, Poland.
AB  - Several studies have shown the month of birth effect on birth weight and height
      of children. The mechanism of this phenomenon is not fully explained. Using data
      from Warsaw hospitals, the influence of four climatic factors (temperature,
      sunlight, humidity and rainfall) on birth outcomes was studied. The sample
      consisted of 10,631 neonates (5450 boys and 5181 girls) born between May 2004 and
      April 2005. Individual values for birth weight and length were standardised on
      the overall mean and standard deviation for all subjects, separately for each
      sex. Differences in means of Z-score birth outcomes between months, seasons and
      semi-annual periods of birth were assessed by one-way analysis of variance,
      separately for each sex. The relation between average values of four atmospheric
      factors and average neonatal outcomes for each month of birth was assessed by a
      weighted Spearman rank correlation. The results revealed significant differences
      in average Z-scores of neonate weight and length between months of birth for boys
      and girls. Significant seasonal variation in Z-scores means was only found for
      birth length in boys. The correlation between four atmospheric factors during
      pregnancy and birth length was the highest for boys and occurred in the second
      trimester. Second trimester of fetal growth is the period most sensitive to
      influences of climatic factors.

PMID- 20813366
TI  - General and abdominal obesity and abdominal visceral fat accumulation associated
      with coronary artery calcification in Korean men.
AB  - OBJECTIVE: It is unclear whether visceral adipose tissue (VAT) is responsible for
      an increased risk of coronary artery calcification (CAC). We evaluated the
      associations between body mass index (BMI), waist circumference (WC) and
      abdominal VAT area with the CAC in healthy Korean men. METHODS: This is a cross
      sectional study of 1336 Korean men free of cardiovascular disease who underwent
      CAC score (CACS) by multislice computed tomography (CT) and abdominal CT as part
      of a routine medical examination. VAT area was measured at the level of the
      umbilicus using CT. RESULTS: Mean BMI, WC, total adipose tissue and VAT area were
      higher in subjects with moderate-to-severe CAC (CACS>100) compared to subjects
      with CACS <= 100. The subjects in the fourth quartile of VAT had significantly
      higher CACS and the greater prevalence of CAC presence and moderate-to-severe CAC
      than those in the first to third quartiles. The highest quartiles of BMI, WC and
      VAT area were significantly associated with moderate-to-severe CAC in the age-
      and CVD risk factor-adjusted model (OR [95% CI]=1.56 [1.11-2.19], 1.56 [1.12
      2.18] and 1.42 [1.01-1.98] with p<0.05 for all, respectively). CONCLUSION: The
      higher levels of general and central measure of obesity and the amount of
      abdominal visceral fat were related to moderate-to-severe CAC in asymptomatic
      Korean men with relatively low risk.

PMID- 20813367
TI  - Feature selection using a principal component analysis of the kinematics of the
      pivot shift phenomenon.
AB  - The pivot shift test reproduces a complex instability of the knee joint following
      rupture of the anterior cruciate ligament. The grade of the pivot shift test has
      been shown to correlate to subjective criteria of knee joint function, return to
      physical activity and long-term outcome. This severity is represented by a grade
      that is attributed by a clinician in a subjective manner, rendering the pivot
      shift test poorly reliable. The purpose of this study was to unveil the kinematic
      parameters that are evaluated by clinicians when they establish a pivot shift
      grade. To do so, eight orthopaedic surgeons performed a total of 127 pivot shift
      examinations on 70 subjects presenting various degrees of knee joint instability.
      The knee joint kinematics were recorded using electromagnetic sensors and
      principal component analysis was used to determine which features explain most of
      the variability between recordings. Four principal components were found to
      account for most of this variability (69%), with only the first showing a
      correlation to the pivot shift grade (r = 0.55). Acceleration and velocity of
      tibial translation were found to be the features that best correlate to the first
      principal component, meaning they are the most useful for distinguishing
      different recordings. The magnitudes of the tibial translation and rotation were
      amongst those that accounted for the least variability. These results indicate
      that future efforts to quantify the pivot shift should focus more on the velocity
      and acceleration of tibial translation and less on the traditionally accepted
      parameters that are the magnitudes of posterior translation and external tibial
      rotation.

PMID- 20813368
TI  - Are allogenic or xenogenic screws and plates a reasonable alternative to
      alloplastic material for osteosynthesis--a histomorphological analysis in a
      dynamic system.
AB  - Despite invention of titanium and resorbable screws and plates, still, one of the
      main challenges in bone fixation is the search for an ideal osteosynthetic
      material. Biomechanical properties, biocompatibility, and also cost effectiveness
      and clinical practicability are factors for the selection of a particular
      material. A promising alternative seems to be screws and plates made of bone.
      Recently, xenogenic bone pins and screws have been invented for use in joint
      surgery. In this study, screws made of allogenic sheep and xenogenic human bone
      were analyzed in a vital and dynamic sheep-model and compared to conventional
      titanium screws over a standard period of bone healing of 56 days with a constant
      applied extrusion force. Biomechanical analysis and histomorphological evaluation
      were performed. After 56 days of insertion xenogenic screws made of human bone
      showed significantly larger distance of extrusion of on average 173.8 MUm
      compared to allogenic screws made of sheep bone of on average 27.8 and 29.95 MUm
      of the titanium control group. Severe resorption processes with connective tissue
      interposition were found in the histomorphological analysis of the xenogenic
      screws in contrast to new bone formation and centripetal vascularization of the
      allogenic bone screw, as well as in processes of incorporation of the titanium
      control group. The study showed allogenic cortical bone screws as a substantial
      alternative to titanium screws with good biomechanical properties. In contrast to
      other reports a different result was shown for the xenogenic bone screws. They
      showed insufficient holding strength with confirmative histomorphological signs
      of degradation and insufficient osseointegration. Before common clinical use of
      xenogenic osteosynthetic material, further evaluation should be performed.

PMID- 20813369
TI  - Validation of a posturographic approach to monitor sleepiness.
AB  - Sleepiness is a major risk factor in traffic- and occupational accidents. While
      sleepiness is a persistent concern, there is no convenient test to monitor
      impending levels of sleepiness. We show that force platform posturographic
      balance testing addresses this need because it estimates time awake (TA)
      accurately and precisely. Testing the TA is appropriate because TA drives the
      sleep homeostatic process, a component in sleepiness. With 12 subjects we
      evaluated the accuracy and precision of repeated estimates of TA. Our extended
      study design that allows evaluating the accuracy and precision of posturographic
      TA-estimates is new. First, we tested the subjects' balance every 2 h during 36 h
      of sustained wakefulness. This comprised the subjects' reference curves (balance
      as a function of known and increasing TA). Then, we tested the subjects' balance
      once a day over one week. We also tested the subjects' balance once a week over
      one month. Finally, to estimate the subjects' TA, we equated the balance scores
      with the scores in their reference curves. The accuracy of the estimates was 86%,
      and the precision was 97%. The high accuracy and precision of the estimates
      obtained with this one-month protocol validates the method of posturographic
      monitoring of sleepiness. So far, force platform posturographic balance testing
      has generally been used for clinical purposes, to quantify balance control and
      musculoskeletal performance. Our main result is that we now validated that
      balance testing provides accurate and precise estimates of TA, and hence, also
      provides an approach towards an automated monitor of sleepiness.

PMID- 20813371
TI  - A novel approach to modelling counter-current chromatography.
AB  - Literature lists a number of counter-current chromatography (CCC) models that can
      predict the retention time and to a certain extent the peak width of a solute
      eluting from a CCC column. The approach described in this paper distinguishes
      itself from previous reports by relating all model parameters directly to column
      dimensions and experimental settings. Most importantly, this model can predict a
      chromatogram from scratch without resorting to traditional calibration using
      empirical values. The model validation with experimental results obtained across
      a range of CCC instruments demonstrated that the solute retention time, peak
      width, and peak resolution could be predicted within reasonable accuracy.
      Additionally, the effect of several process parameters, such as mobile phase flow
      rate, rotational speed of the column or beta-value, showed that the model is
      robust and applicable to a wide range of CCC instruments. Overall, this model
      proved to be a useful tool for parameter estimation and, most significantly,
      separation optimisation.

PMID- 20813372
TI  - Numerical modeling of elution peak profiles in supercritical fluid
      chromatography. Part I--elution of an unretained tracer.
AB  - When chromatography is carried out with high-density carbon dioxide as the main
      component of the mobile phase (a method generally known as "supercritical fluid
      chromatography" or SFC), the required pressure gradient along the column is
      moderate. However, this mobile phase is highly compressible and, under certain
      experimental conditions, its density may decrease significantly along the column.
      Such an expansion absorbs heat, cooling the column, which absorbs heat from the
      outside. The resulting heat transfer causes the formation of axial and radial
      gradients of temperature that may become large under certain conditions. Due to
      these gradients, the mobile phase velocity and most physico-chemical parameters
      of the system (viscosity, diffusion coefficients, etc.) are no longer constant
      throughout the column, resulting in a loss of column efficiency, even at low flow
      rates. At high flow rates and in serious cases, systematic variations of the
      retention factors and the separation factors with increasing flow rates and
      important deformations of the elution profiles of all sample components may
      occur. The model previously used to account satisfactorily for the effects of the
      viscous friction heating of the mobile phase in HPLC is adapted here to account
      for the expansion cooling of the mobile phase in SFC and is applied to the
      modeling of the elution peak profiles of an unretained compound in SFC. The
      numerical solution of the combined heat and mass balance equations provides
      temperature and pressure profiles inside the column, and values of the retention
      time and efficiency for elution of this unretained compound that are in excellent
      agreement with independent experimental data.

PMID- 20813373
TI  - Extraction of essential oils from Algerian myrtle leaves using instant controlled
      pressure drop technology.
AB  - In the present work, the new extraction process of Detente Instantanee Controlee
      DIC (French, for instant controlled pressure drop) was studied, developed,
      quantitatively and qualitatively compared to the conventional hydrodistillation
      method for the extraction of essential oils from Algerian myrtle leaves. DIC was
      used as a thermomechanical treatment, DIC subjecting the product to a high
      pressure saturated steam. The DIC cycle ends with an abrupt pressure drop towards
      vacuum, and this instantly leads to an autovaporization of myrtle volatile
      compounds. An immediate condensation in the vacuum tank produced a micro-emulsion
      of water and essential oils. Thus, an ultra-rapid cooling of residual leaves
      occurred, precluding any thermal degradation. An experimental protocol was
      designed with 3 independent variables: saturated steam pressure between 0.1 and
      0.6 MPa, resulting in a temperature between 100 and 160 degrees C, a total
      thermal processing time between 19 and 221 s, and between 2 and 6 DIC cycles. The
      essential oils yield was defined as the main dependent variable. This direct
      extraction gave high yields and high quality essential oil, as revealed by
      composition and antioxidant activity (results not shown). After this treatment,
      the myrtle leaves were recovered and hydrodistilled in order to quantify the
      essential oil content in residual DIC-treated samples. Scanning electron
      microscope (SEM) showed some modification of the structure with a slight
      destruction of cell walls after DIC treatment.

PMID- 20813374
TI  - Relationship between trans-column eddy diffusion and retention in liquid
      chromatography: theory and experimental evidence.
AB  - Experimental results demonstrate that trans-column eddy diffusion depends on the
      retention of compounds. The combination of elution profiles recorded in different
      points of the exit column cross-section and of the height equivalent to a
      theoretical plate (HETP) of small molecules clearly show a strong link between
      retention and column performance in liquid chromatography. These results validate
      a new model of trans-column eddy diffusion in packed columns. The contribution to
      the column HETP of the trans-column eddy diffusion term decreases with increasing
      retention factor from k'=0 to k'=3 above which it becomes negligible. The best
      column performance in RPLC is observed for the most retained compounds. This is
      due to the combination of the lack of a residual trans-column eddy diffusion
      contribution and the vanishing contribution of the instrument to band broadening.

PMID- 20813375
TI  - Complementary fragmentation pattern analysis by gas chromatography-mass
      spectrometry and liquid chromatography tandem mass spectrometry confirmed the
      precious lignan content of Cirsium weeds.
AB  - In this paper, as novelties to the field, it is confirmed at first, that the
      fruits of Cirsium species, regarded as injurious weeds, do contain lignans, two,
      different butyrolactone-type glycoside/aglycone pairs: the well known
      arctiin/arctigenin and the particularly rare tracheloside/trachelogenin species.
      These experiences were supported by gas chromatography-mass spectrometry (GC-MS),
      by liquid chromatography tandem mass spectrometry (LC-MS/(MS)) and by nuclear
      magnetic resonance (NMR) spectroscopy. The study reflects the powerful impact of
      the complementary chromatographic mass fragmentation evidences resulting in the
      identification and quantification, the extremely rare, with on line technique not
      yet identified and described, tracheloside/trachelogenin pair lignans, without
      authentic standard compounds. Fragmentation pattern analysis of the
      trimethylsilyl (TMS) derivative of trachelogenin, based on GC-MS, via two
      different fragmentation pathways confirmed the detailed structure of the
      trachelogenin molecule. The complementary chromatographic evidences have been
      unambiguously confirmed, by (1)H and (13)C NMR analysis of trachelogenin,
      isolated by preparative chromatography. Identification and quantification of the
      fruit extracts of four Cirsium (C.) species (C. arvense, C. canum, C. oleraceum,
      and C. palustre), revealed that (i) all four species do accumulate the
      tracheloside/trachelogenin or the arctiin/arctigenin butyrolactone-type
      glycoside/aglycone pairs, (ii) the overwhelming part of lignans are present as
      glycosides (tracheloside 9.1-14.5 mg/g, arctiin 28.6-39.3 mg/g, expressed on dry
      fruit basis), (iii) their acidic and enzymatic hydrolyses to the corresponding
      aglycones, to trachelogenin and arctigenin are fast and quantitative and (iv) the
      many-sided beneficial trachelogenin and arctigenin can be prepared separately,
      without impurities, excellent for medicinal purposes.

PMID- 20813376
TI  - Optimization of an anion-exchange high performance liquid chromatography
      inductively coupled plasma-mass spectrometric method for the speciation analysis
      of oxyanion-forming metals and metalloids in leachates from cement-based
      materials.
AB  - A method was developed for the speciation analysis of the oxyanions of As(III),
      As(V), Cr(VI), Mo(VI), Sb(III), Sb(V), Se(IV), Se(VI) and V(V) in leachates from
      cement-based materials, based on anion-exchange HPLC coupled with ICP-MS. The
      method was optimized in a two-step multivariate approach: the effect of sample pH
      and mobile phase composition on resolution, peak symmetry and analysis time was
      studied. Optimum conditions were then identified for the significant experimental
      factors by studying their interdependence. A mobile phase composition of 20 mM
      ammonium nitrate, 50 mM ammonium tartrate and pH 9.5 was found to be a compromise
      optimum for the separation of the target analytes using isocratic elution. The
      optimum condition provided separation of the analytes in less than 6 min, at a
      mobile phase flow rate of 1.0 mL/min. The signal intensities of the analytes were
      improved by adding 1% methanol to the mobile phase. The limit of detection of the
      method was in the range 0.2-2.2 MUg/L for the various species. The effect of
      sample constituents was studied using spiked concrete leachates. The method was
      used to determine the target oxyanionic species in leachates generated from a
      concrete material in the pH range 3.5-12.4; CrO(4)(2-), MoO(4)(2-) and VO(4)(3-)
      were detected in most of the leachates.

PMID- 20813377
TI  - Finite reservoir effect on capillary flow of microbead suspension in rectangular
      microchannels.
AB  - The present study reports a theoretical investigation of capillary transport of
      microbead suspension in microfluidic channels with finite size reservoirs at the
      inlet. The reservoir-microchannel combination is often the case in Lab-on-a-Chip
      (LOC) where biomolecules are transported using capillary force. To demonstrate
      such finite reservoir effect, the reservoir is placed vertically above the
      microchannel. Under such condition, the pressure field expression at the
      rectangular microchannel inlet is deduced. Appropriate correlations for effective
      physical properties are used to account for the presence of microbeads in the
      working fluid, mimicking biomolecules in actual LOC. The non-dimensional
      governing equation for capillary flow with finite size reservoir is derived based
      on the balance among the surface, viscous and gravity forces acting on the fluid
      front. The numerical solution of governing equation is obtained to investigate
      the impact of several operating parameters on the flow front progression. It is
      observed that the aspect ratio of the microchannel and reservoir play vital roles
      in deciding the behavior and magnitude of flow front progression in the
      microfluidic channels. Capillarity and gravity force dominant regions during the
      progression is observed. The microchannel width and reservoir width decide the
      interplay between gravity and capillarity. Although higher fluid level in the
      reservoir has an added advantage for more gravitational head, the resistance from
      the reservoir makes the flow front progress slowly at the beginning of the
      capillary transport. It is also found that microbead volume fraction in the
      working fluid plays an important role in delaying the capillary transport under
      various operating conditions. Hence, it can be concluded that the use of
      reservoir at the inlet of microfluidic channels has an impact on the overall
      capillary transport of biomolecules in LOC devices.

PMID- 20813378
TI  - Effects of equine herpesvirus-9 infection in pregnant mice and hamsters.
AB  - The pathogenicity of equine herpesvirus (EHV)-9, a new neurotropic equine
      herpesvirus isolated from gazelles, was assessed in pregnant rodents (mice and
      hamsters) following intranasal inoculation. The pregnant female mice and hamsters
      were inoculated with EHV-9 in the early or late trimesters. The inoculated
      animals exhibited mild to severe neurological signs and gave birth to dead or
      undersized fetuses. All three mice and four hamsters inoculated in the first
      trimester had varying degrees of placental abnormality, characterized by markedly
      dilated maternal blood sinusoids, atrophy of the trophoblast cells and necrosis
      of the middle layer of the trophoblast. There was also endometrial blood vessel
      congestion and necrosis and disorganization of the fetal capillaries in the mice
      and hamsters inoculated in the last trimester. EHV-9 antigen was detected in the
      brain of dams and the lungs of the fetuses and in the middle of the trophoblast
      layer of the placenta in hamsters inoculated in the first trimester. The
      placental lesions were milder in mice than in the hamsters. The mice and hamsters
      inoculated in the last trimester had more prominent lesions than the animals
      inoculated in the first trimester. These results suggest that EHV-9 can cause the
      death of the fetus or abortion and that these events may be secondary to
      placental vascular compromise.

PMID- 20813379
TI  - Chronic Lyme disease: a survey of Connecticut primary care physicians.
AB  - OBJECTIVE: To determine how frequently Connecticut primary care physicians are
      diagnosing and treating patients with chronic Lyme disease. STUDY DESIGN: A
      survey was mailed to a random 33% sample of primary care physicians in
      Connecticut, which asked how many cases of Lyme disease and chronic Lyme disease
      they diagnosed and treated in the last 3 years. RESULTS: The survey had a
      response rate of 39.1%. Physician respondents (n = 285) fit in one of 3 groups.
      Group 1 included 6 of 285 (2.1%) physicians who diagnose and treat patients with
      chronic Lyme disease. Group 2 included 137 of 285 (48.1%) physicians who are
      undecided on the existence of chronic Lyme disease, but did not diagnose or treat
      any patients with chronic Lyme disease. Group 3 included 142 of 285 (49.8%)
      physicians who do not believe in the existence of chronic Lyme disease.
      CONCLUSION: A small percentage (2.1%) of primary care physicians diagnose and
      treat patients for presumed chronic Lyme disease.

PMID- 20813380
TI  - The need for more research on seizures in preterm infants.

PMID- 20813381
TI  - School performance of childhood cancer survivors: mind the teenagers!
AB  - OBJECTIVE: To assess school performance in an unselected group of childhood
      cancer survivors and study risk factors for impairment. STUDY DESIGN: Rates of
      repeating a grade were compared for patients with cancer, their siblings, and the
      general population. Phone questionnaires were administered to patients about the
      school career of their child in remission and their siblings. Responses about
      cancer survivors were compared with those concerning their siblings and various
      registries provided by the national board of education. The primary outcome was
      the rate of repeating a grade. RESULTS: A total of 148 children in remission with
      a mean age of 15 +/- 5.3 years and a mean follow-up period since diagnosis of 6.3
      +/- 1.3 years were included. More patients than siblings repeated a grade (33%
      versus 21%; P = .02), with a mean delay since diagnosis of 2 years. Risk factors
      were an older age at diagnosis, attending a secondary school, low education level
      of parents, bone marrow transplantation, cerebral surgery, and physical sequelae.
      In multivariate analysis, risk for repeating was associated with low educational
      level of the father, attending secondary school at diagnosis, and requiring
      school-organized educational support on return to school. CONCLUSION: After
      cancer, repeating a grade is not an exceptional occurrence, especially for
      teenagers; follow-up and supportive interventions before returning to school
      would be beneficial.

PMID- 20813382
TI  - Exercise performance in adolescents with autonomic dysfunction.
AB  - OBJECTIVE: To test the hypothesis that excessive postural tachycardia is
      associated with deconditioning rather than merely being an independent sign of
      autonomic dysfunction in patients with postural orthostatic tachycardia syndrome
      (POTS). STUDY DESIGN: We retrospectively analyzed records from 202 adolescents
      who underwent both head up-tilt and maximal exercise testing. Patients were
      classified as POTS if they had >= 30 min(-1) rise in heart rate (HR) after tilt
      table test; and deconditioned if peak O(2) uptake was < 80% predicted. Changes in
      HR during exercise and recovery were compared between groups. RESULTS: Two-thirds
      of patients were deconditioned, irrespective of whether they fulfilled diagnostic
      criteria for POTS, but peak O(2) uptake among patients with POTS was similar to
      patients without POTS. HR was higher at rest and during exercise; whereas stroke
      volume was lower during exercise, and HR recovery was slower in patients with
      POTS compared with patients without POTS. CONCLUSIONS: Most patients who
      presented with chronic symptoms of dizziness, fatigue, or pre-syncope, were
      deconditioned, but, because the proportion of deconditioned patients was similar
      in POTS vs non-POTS groups, we conclude that HR changes in POTS are not solely
      because of inactivity resulting in deconditioning.

PMID- 20813383
TI  - Characterization of the metabolic and physiologic response to chromium
      supplementation in subjects with type 2 diabetes mellitus.

PMID- 20813384
TI  - Lupin pyranoisoflavones inhibiting hyphal development in arbuscular mycorrhizal
      fungi.
AB  - White lupin (Lupinus albus L.), a non-host plant for arbuscular mycorrhizal (AM)
      fungi in the typically mycotrophic family Fabaceae, has been investigated for
      root metabolites that inhibit hyphal development in AM fungi. Four known
      pyranoisoflavones, licoisoflavone B (1), sophoraisoflavone A (2),
      alpinumisoflavone (3) and 3'-hydroxy-4'-O-methylalpinumisoflavone (4), together
      with three previously unknown pyranoisoflavones, lupindipyranoisoflavone A (5),
      10'-hydroxylicoisoflavone B (6) and 10'-hydroxysophoraisoflavone A (7) were
      isolated from the root exudates of white lupin as an inhibitor of germ tube
      growth in the AM fungus Gigaspora margarita. Pyranoisoflavones 1, 2 and 3
      strongly inhibited germ tube growth at 0.63, 1.25 and 0.63 MUg/disc,
      respectively. The remaining compounds 4-7 were either moderate or weak inhibitors
      that inhibited germ tube growth at concentrations higher than 10 MUg/disc.
      Licoisoflavone B (1) and sophoraisoflavone A (2) completely inhibited hyphal
      branching induced by a lupin strigolactone, orobanchyl acetate, in G. margarita
      at 0.16 and 0.63 MUg/disc, respectively.

PMID- 20813385
TI  - Diagnostic criteria for multiple system atrophy and progressive supranuclear
      palsy.
AB  - The atypical parkinsonian disorders (APD) embrace a heterogeneous group of
      movement disorders all characterized by prominent parkinsonism, accompanied by
      specific additional features such as cerebellar ataxia, early autonomic
      dysfunction, early dementia, pyramidal tract signs, myoclonus, supranuclear gaze
      palsy, apraxia which are atypical for idiopathic Parkinson's disease (PD). Beside
      these features, rapid disease progression and poor or absent response to L-Dopa
      therapy both raise the suspicion of an APD. Currently, multiple system atrophy
      (MSA), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and
      dementia with Lewy bodies (DLB) are referred to as APD. Clinical diagnosis can be
      difficult in early stages and although the predictive value of the widely
      established, diagnostic criteria is high at first neurological evaluation
      sensitivity tends to be poor and may be less than 30%. In this review, we will
      discuss diagnostic issues in MSA and PSP.

PMID- 20813386
TI  - [How to manage daytime sleepiness associated with Parkinson's disease].
AB  - Excessive daytime sleepiness (EDS) is frequent in Parkinson's disease. It should
      be explored by an Epworth sleepiness scale, a nighttime sleep recording and
      multiple sleep latency tests. EDS can be secondary to disturbed nighttime sleep
      that should be explored first. The main reasons for nighttime sleep disturbances
      are pain, nocturia, restless legs syndrome, obstructive sleep apnea syndrome and
      depression. They should be treated step by step. EDS can also be secondary to
      antiparkinsonian dopaminergic treatments that can induce nighttime insomnia
      and/or daytime sleepiness sometimes with sleep attacks. Treatment modifications
      and, when indicated, deep brain stimulation can improve these symptoms.
      Furthermore, EDS can be secondary to the disease itself modifying the sleep wake
      regulation systems. When the treatment of disturbed nighttime sleep and
      adjustments of the dopaminergic treatments are not sufficient to improve EDS,
      wake promoting treatments can be used. Their efficacy is variable but new hopeful
      drugs are coming soon.

PMID- 20813387
TI  - A network population model of the dynamics and control of African malaria
      vectors.
AB  - A more robust assessment of malaria control through mosquito larval habitat
      destruction will come from a better understanding of the distribution,
      productivity and connectivity of breeding sites. The present study examines the
      significance of vector dispersal ability, larval habitat stability and
      productivity on the persistence and extinction of a mosquito population
      inhabiting a dynamic network of breeding sites. We use this novel method of
      vector modelling to show that when dispersal is limited or vector distribution is
      patchy, the spread and growth of a mosquito population at the onset of a rainy
      season is delayed and extinction through larval habitat destruction is more
      readily achieved. We also determine the impact of two alternative dry-season
      survival strategies on mosquito dynamics. Simulations suggest that if adult
      vectors remain dormant throughout the dry season, the stage structure of the
      population will be synchronized at the onset of the wet season and its growth
      will be delayed. In contrast, a population that continues to breed throughout the
      dry season grows more rapidly and is more difficult to control. Our findings have
      important implications on the development of integrative malaria vector
      management strategies and on the understanding of dry-season survival mechanisms
      of African malaria vectors.

PMID- 20813388
TI  - Climate change, flooding, urbanisation and leptospirosis: fuelling the fire?
AB  - Flooding and heavy rainfall have been associated with numerous outbreaks of
      leptospirosis around the world. With global climate change, extreme weather
      events such as cyclones and floods are expected to occur with increasing
      frequency and greater intensity and may potentially result in an upsurge in the
      disease incidence as well as the magnitude of leptospirosis outbreaks. In this
      paper, we examine mechanisms by which climate change can affect various
      ecological factors that are likely to drive an increase in the overall incidence
      as well as the frequency of outbreaks of leptospirosis. We will discuss the
      geographical areas that are most likely to be at risk of an increase in
      leptospirosis disease burden owing to the coexistence of climate change hazard
      risk, environmental drivers of leptospirosis outbreaks, local socioeconomic
      circumstances, and social and demographic trends. To reduce this disease burden,
      enhanced surveillance and further research is required to understand the
      environmental drivers of infection, to build capacity in emergency response and
      to promote community adaptation to a changing climate.

PMID- 20813389
TI  - The unsolved mystery of Johann Georg Wirsung and of (his?) pancreatic duct.

PMID- 20813390
TI  - HPV-16 E5 down-regulates expression of surface HLA class I and reduces
      recognition by CD8 T cells.
AB  - HPV-16 is the major causes of cervical cancer. Persistence of infection is a
      necessary event for progression of the infection to cancer. Among other factors,
      virus persistence is due the viral proteins fighting the immune response. HPV-16
      E5 down-regulates MHC/HLA class I, which is much reduced on the cell surface and
      accumulates in the Golgi apparatus in cells expressing E5. This effect is
      observed also in W12 cells, which mimic early cervical intraepithelial
      progression to cervical cancer. The functional effect of MHC I down-regulation on
      human CD8 T cells is not known, because of the need for HLA-matched, HPV-specific
      T cells that recognise E5 expressing-cells. Here we employ a heterologous
      cell/MHC I system which uses mouse cells expressing both E5 and HLA-A2, and A2
      restricted CTLs; we show that the E5-induced reduction of HLA-A2 has a functional
      impact by reducing recognition of E5 expressing cells by HPV specific CD8+ T
      cells.

PMID- 20813391
TI  - Asset deterioration and discolouration in water distribution systems.
AB  - Water Distribution Systems function to supply treated water safe for human
      consumption and complying with increasingly stringent quality regulations.
      Considered primarily an aesthetic issue, discolouration is the largest cause of
      customer dissatisfaction associated with distribution system water quality. Pro
      active measures to prevent discolouration are sought yet network processes remain
      insufficiently understood to fully justify and optimise capital or operational
      strategies to manage discolouration risk. Results are presented from a
      comprehensive fieldwork programme in UK water distribution networks that have
      determined asset deterioration with respect to discolouration. This is achieved
      by quantification of material accumulating as cohesive layers on pipe surfaces
      that when mobilised are acknowledged as the primary cause of discolouration. It
      is shown that these material layers develop ubiquitously with defined layer
      strength characteristics and at a consistent and repeatable rate dependant on
      water quality. For UK networks iron concentration in the bulk water is shown as a
      potential indicator of deterioration rate. With material layer development rates
      determined, management decisions that balance discolouration risk and expenditure
      to maintain water quality integrity can be justified. In particular the balance
      between capital investment such as improving water treatment output or pipe
      renewal and operational expenditure such as the frequency of network maintenance
      through flushing may be judged. While the rate of development is shown to be a
      function of water quality, the magnitude (peak or average turbidity) of
      discolouration incidents is shown to be dominated by hydraulic conditions. From
      this it can be proposed that network hydraulic management, such as regular
      periodic 'stressing', is a potential strategy in reducing discolouration risk.
      The ultimate application of this is the hydraulic design of self-cleaning
      networks to maintain discolouration risk below acceptable levels.

PMID- 20813392
TI  - Fate of aniline and sulfanilic acid in UASB bioreactors under denitrifying
      conditions.
AB  - Two upflow anaerobic sludge blanket (UASB) reactors were operated to investigate
      the fate of aromatic amines under denitrifying conditions. The feed consisted of
      synthetic wastewater containing aniline and/or sulfanilic acid and a mixture of
      volatile fatty acids (VFA) as the primary electron donors. Reactor 1 (R1)
      contained a stoichiometric concentration of nitrate and Reactor 2 (R2) a
      stoichiometric nitrate and nitrite mixture as terminal electron acceptors. The R1
      results demonstrated that aniline could be degraded under denitrifying conditions
      while sulfanilic acid remains. The presence of nitrite in the influent of R2,
      caused a chemical reaction that led to immediate disappearance of both aromatic
      amines and the formation of an intense yellow coloured solution. HPLC analysis of
      the influent solution, revealed the emergence of three product peaks: the major
      one at retention time (R(t)) 14.3 min and two minor at R(t) 17.2 and 21.5 min. In
      the effluent, the intensity of the peaks at R(t) 14.3 and 17.2 min was very low
      and of that at R(t) 21.5 min increased (~3-fold). Based on the mass spectrometry
      analysis, we propose the structures of some possible products, mainly azo
      compounds. Denitrification activity tests suggest that biomass needed to adapt to
      the new coloured compounds, but after a 3 days lag phase, activity is recovered
      and the final (N(2) + N(2)O) is even higher than that of the control.

PMID- 20813393
TI  - Photosensitized degradation of amoxicillin in natural organic matter isolate
      solutions.
AB  - Amoxicillin is a widely used antibiotic and has been detected in natural waters.
      Its environmental fate is in part determined by hydrolysis, and, direct and
      indirect photolysis. The hydrolysis rate in distilled water and water to which
      five different isolated of dissolved organic matter (DOM) was added, were
      evaluated. In the five different DOM solutions hydrolysis accounted for 5-18%
      loss of amoxicillin. Direct and indirect photolysis rates were determined using a
      solar simulator and it appeared that indirect photolysis was the dominant loss
      mechanism. Direct photolysis, in a solar simulator, accounted for 6-21% loss of
      amoxicillin in the simulated natural waters. The steady-state concentrations of
      singlet oxygen, (1)DeltaO(2) (~10(-13) M) and hydroxyl radical, *OH (~10(-17) M)
      were obtained in aqueous solutions of five different dissolved organic matter
      samples using a solar simulator. The bimolecular reaction rate constant of
      (1)DeltaO(2) with amoxicillin was measured in the different solutions,
      k(DeltaO(2)) = 1.44 * 10(4) M(-1) s(-1). The sunlight mediated amoxicillin loss
      rate with (1)DeltaO(2) (~10(-9) s(-1)), and with *OH (~10(-7) s(-1)), were also
      determined for the different samples of DOM. While (1)DeltaO(2) only accounted
      for 0.03-0.08% of the total loss rate, the hydroxyl radical contributed 10-22%.
      It appears that the direct reaction of singlet and triplet excited state DOM
      ((3)DOM(*)) with amoxicillin accounts for 48-74% of the loss of amoxicillin.
      Furthermore, the pseudo first-order photodegradation rate showed a positive
      correlation with the sorption of amoxicillin to DOM, which further supported the
      assumption that excited state DOM* plays a key role in the photochemical
      transformation of amoxicillin in natural waters. This is the first study to
      report the relative contribution of all five processes to the fate of amoxicillin
      in aqueous solution.

PMID- 20813394
TI  - An initial study to assess the use of geological parent materials to predict the
      Se concentration in overlying soils and in five staple foodstuffs produced on
      them in Scotland.
AB  - Evidence suggests that dietary-intakes of the essential element selenium have
      fallen in Scotland in recent years, due to changing sources of bread-making
      wheat. The Scottish environment is thought to be Se-poor due to the geology and
      climate. This initial study assessed whether geological parent-materials could be
      used to predict relatively high and low soil-Se areas in Scotland and whether
      differences in soil-Se were reflected in foodstuff-Se produced on them. Samples
      (n=8 per farm) of wheat, calabrese (broccoli), potato, beef-steak, milk, cattle
      pasture (grass) and soil were collected from pairs of farms (one in each high/low
      predicted Se area (PSA)). Potatoes and soils were collected from a further 34
      farms in high/low PSAs to assess a greater geographical zone. Total soil-Se
      ranged from 0.115 to 0.877mgkg(-1) but most samples (90%) could be classed as Se
      deficient (<0.6mgkg(-1)), irrespective of PSA. Total soil-Se was significantly
      higher (p<0.05) in the high than in the low PSAs as expected; however, the
      difference between the two was small (mean 0.48 and 0.37mgkg(-1), respectively).
      Water-soluble soil-Se (6.69 to 26.78MUgkg(-1)) concentrations were not
      significantly different between the two PSAs (p=0.71). Soil loss-on-ignition
      (indicating organic matter content) correlated significantly with total and water
      soluble soil-Se (p<0.001) and exerted a greater control than parent-material on
      soil-Se. Significant differences between the PSAs for beef-Se (p<0.001), wheat-Se
      (p<0.001), calabrese-Se (p<0.01) and beef-farm grass-Se (p<0.05) indicated
      partial success of the parent-material soil-Se prediction. However, only wheat-Se
      (p<0.001) and potato-Se (p<0.001) correlated significantly with total soil-Se.
      The results suggest that soil-Se concentrations in the main agricultural areas of
      Scotland are generally low. Given the low Se concentrations also reported in the
      food commodities; further investigations may be warranted to fully characterise
      the Se-status of Scottish produce and dietary-Se intakes in Scotland.

PMID- 20813395
TI  - The chronic toxicity of molybdate to freshwater organisms. I. Generating reliable
      effects data.
AB  - The European Union regulation on Registration, Evaluation, Authorization and
      Restriction of Chemical substances (REACH) (EC, 2006) requires the
      characterization of the chronic toxicity of many chemicals in the aquatic
      environment, including molybdate (MoO(4)(2-)). Our literature review on the
      ecotoxicity of molybdate revealed that a limited amount of reliable chronic no
      observed effect concentrations (NOECs) for the derivation of a predicted no
      effect concentration (PNEC) existed. This paper presents the results of
      additional ecotoxicity experiments that were conducted in order to fulfill the
      requirements for the derivation of a PNEC by means of the scientifically most
      robust species sensitivity distribution (SSD) approach (also called the
      statistical extrapolation approach). Ten test species were chronically exposed to
      molybdate (added as sodium molybdate dihydrate, Na(2)MoO(4).2H(2)O) according to
      internationally accepted standard testing guidelines or equivalent. The 10%
      effective concentrations (EC10, expressed as measured dissolved molybdenum) for
      the most sensitive endpoint per species were 62.8-105.6 (mg Mo)/L for Daphnia
      magna (21day-reproduction), 78.2 (mg Mo)/L for Ceriodaphnia dubia (7day
      reproduction), 61.2-366.2 (mg Mo)/L for the green alga Pseudokirchneriella
      subcapitata (72h-growth rate), 193.6 (mg Mo)/L for the rotifer Brachionus
      calyciflorus (48h-population growth rate), 121.4 (mg Mo)/L for the midge
      Chironomus riparius (14day-growth), 211.3 (mg Mo)/L for the snail Lymnaea
      stagnalis (28day-growth rate), 115.9 (mg Mo)/L for the frog Xenopus laevis (4day
      larval development), 241.5 (mg Mo)/L for the higher plant Lemna minor (7day
      growth rate), 39.3 (mg Mo)/L for the fathead minnow Pimephales promelas (34day
      dry weight/biomass), and 43.2 (mg Mo)/L for the rainbow trout Oncorhynchus mykiss
      (78day-biomass). These effect concentrations are in line with the few reliable
      data currently available in the open literature. The data presented in this study
      can serve as a basis for the derivation of a PNEC(aquatic) that can be used for
      national and international regulatory purposes and for setting water quality
      criteria. Using all reliable data that are currently available, a HC(5,50%)
      (median hazardous concentration affecting 5% of the species) of 38.2 (mg Mo)/L
      was derived with the statistical extrapolation approach.

PMID- 20813396
TI  - Acute cigarette smoke exposure reduces clot lysis--association between altered
      fibrin architecture and the response to t-PA.
AB  - BACKGROUND: Enhanced thrombolysis is a proposed mechanism for reduced mortality
      in cigarette smokers with STEMI ("smoker's paradox"). The mechanisms remain
      unclear but studies suggest fibrin architecture (FA) may affect thrombolysis. Our
      group has previously shown that acute cigarette smoke exposure (CSE) alters FA.
      This study was done to evaluate the association between FA, thrombolysis and CSE.
      METHODS AND RESULTS: Otherwise healthy smokers (n=22) were studied before and
      after smoking two cigarettes. Non-smokers (n=22) served as controls. Two ex-vivo
      models were used to evaluate clot lysis of venous blood and these data were
      compared to FA as determined by SEM. In the first model, clot lysis in a glass
      tube at 60minutes after addition of t-PA was measured. The second model
      quantified lysis utilizing thromboelastography. With the latter, after a clot
      reached maximum strength, t-PA was added and clot lysis at 60min was noted. SEM
      studies were performed on platelet poor plasma mixed with thrombin and FA was
      examined at 20K. Clot lysis was similar in both groups except that post-smoking,
      TEG showed a significantly lower lysis compared to pre- and non-smoking clots.
      SEM analysis showed significantly thinner fibers and denser clots post-smoking.
      CONCLUSIONS: Venous clots from smokers failed to show an enhanced lysis when
      exposed to t-PA. In fact, acute CSE was associated with changes in FA and
      increased resistance to thrombolysis. These findings in part may explain enhanced
      thrombogenicity but suggest that mechanisms other than enhanced fibrinolysis are
      likely to be responsible for "smoker's paradox."

PMID- 20813397
TI  - Bleeding reduction during secondary prophylaxis with bypassing agents in
      inhibitor patients.

PMID- 20813398
TI  - Making the right choice: optimizing rt-PA and eptifibatide lysis, an in vitro
      study.
AB  - INTRODUCTION: Recombinant tissue plasminogen activator (rt-PA) is the only FDA
      approved lytic therapy for acute ischemic stroke. However, there can be
      complications such as intra-cerebral hemorrhage. This has led to interest in
      adjuncts such as GP IIb-IIIa inhibitors. However, there is little data on
      combined therapies. Here, we measure clot lysis for rt-PA and eptifibatide in an
      in vitro human clot model, and determine the drug concentrations maximizing
      lysis. A pharmacokinetic model is used to compare drug concentrations expected in
      clinical trials with those used here. The hypothesis is that there is a range of
      rt-PA and eptifibatide concentrations that maximize in vitro clot lysis.
      MATERIALS AND METHODS: Whole blood clots were made from blood obtained from 28
      volunteers, after appropriate institutional approval. Sample clots were exposed
      to rt-PA and eptifibatide in human fresh-frozen plasma; rt-PA concentrations were
      0, 0.5, 1, and 3.15 MUg/ml, and eptifibatide concentrations were 0, 0.63, 1.05,
      1.26 and 2.31 MUg/ml. All exposures were for 30 minutes at 37 C. Clot width was
      measured using a microscopic imaging technique and mean fractional clot loss
      (FCL) at 30 minutes was used to determine lytic efficacy. On average, 28 clots
      (range: 6-148) from 6 subjects (3-24) were used in each group. RESULTS AND
      CONCLUSIONS: FCL for control clots was 14% (95% Confidence Interval: 13-15%). FCL
      was 58% (55-61%) for clots exposed to both drugs at all concentrations, except
      those at an rt-PA concentration of 3.15 MUg/ml, and eptifibatide concentrations
      of 1.26 MUg/ml (Epf) or 2.31 MUg/ml. Here, FCL was 43% (36-51) and 35% (32-38)
      respectively. FCL is maximized at moderate rt-PA and eptifibatide concentration;
      these values may approximate the average concentrations used in some rt-PA and
      eptifibatide treatments.

PMID- 20813399
TI  - Purification and characterization of a novel anticoagulant and fibrinolytic
      enzyme produced by endophytic bacterium Paenibacillus polymyxa EJS-3.
AB  - INTRODUCTION: Endophytes may become a new source of thrombolytic agents for
      thrombosis treatment. MATERIALS AND METHODS: A novel fibrinolytic enzyme from
      Paenibacillus polymyxa EJS-3 (PPFE-I) was purified with ammonium sulfate
      precipitation, hydrophobic chromatography, ion exchange and gel filtration
      chromatography. The characterization of the enzyme was investigated by means of
      fibrinolysis plate, hydrolysis of fibrinogen and anticoagulant effect in vitro.
      RESULTS: The fibrinolytic enzyme is purified to homogeneity with a purification
      of 14.5 fold and a recovery of 3.3%. The enzyme was shown to have a molecular
      mass of 63.3kDa by matrix assisted laser desorption ionization time-of-flight
      mass spectrometry (MALDI-TOF-MS). The optimum temperature and pH value were 37
      degrees C and 7.5, respectively. Results from the fibrinolysis pattern showed
      that the enzyme rapidly hydrolyzed the Aalpha-chain of fibrinogen, followed by
      the Bbeta-chains. It also hydrolyzed the gamma-chains, but more slowly. It was
      activated by metal ions such as Zn(2+), Mg(2+), and Fe(2+), but inhibited by
      Ca(2+) and Cu(2+). Furthermore, PPFE-I activity was inhibited strongly by PMSF,
      and it was found to exhibit a higher specificity for the synthetic substrate N
      succinyl-Ala-Ala-Pro-Phe-pNA for chymotrypsin, indicating that the enzyme is a
      chymotrypsin-like serine protease. Additionly, PPFE-I showed a significant
      anticoagulant effect in vitro. CONCLUSION: The fibrinolytic enzyme PPFE-I from
      endophytic bacterium Paenibacillu polymyxa EJS-3 exhibits a profound fibrinolytic
      activity.

PMID- 20813400
TI  - Transverse testicular ectopia associated with persistent Mullerian duct syndrome:
      another entity in which magnetic resonance imaging is unreliable.
AB  - In this case report we describe a case of persistant Mullerian duct syndrome
      together with transverse testicular ectopia. These 2 entities are discussed to
      assess the relationship between them and the lack of necessity for magnetic
      resonance imaging in cases of undescended testes, and relevant literature is
      reviewed.

PMID- 20813401
TI  - Fatigue of zirconia and dental bridge geometry: Design implications.
AB  - Zirconia is currently used as a framework material for posterior all-ceramic
      bridges. While the majority of research efforts have focused on the
      microstructure and corresponding mechanical properties of this material, clinical
      fractures appear to be largely associated with the appliance geometry. OBJECTIVE:
      The objective of this study was to estimate the maximum stress concentration
      posed by the connector geometry and to provide adjusted estimates of the minimum
      connector diameter that is required for achieving 20 years of function. METHODS:
      A simple quantitative description of the connector geometry in an all-ceramic 4
      unit bridge design is used with published stress concentration factor charts to
      estimate the degree of stress concentration and the maximum stress. RESULTS: The
      magnitude of stress concentration estimated for clinically relevant connector
      geometries ranges from 2 to 3. Using previously published recommendations for
      connector designs, adjusted estimates for the minimum connector diameter required
      to achieve 20 years of clinical function are presented. SIGNIFICANCE: To prevent
      clinical fractures the minimum connector diameter in multi-unit bridges designs
      must account for the loads incurred during function and the extent of stress
      concentration posed by the connector geometry.

PMID- 20813402
TI  - The role of religious involvement on depression, risky behavior, and academic
      performance among Korean American adolescents.
AB  - Structural equation modeling was used to test a theoretical path model of church
      engagement, personal spirituality, and mentoring relationships on depressive
      symptoms, involvement in risky behaviors, and self-reported grades among Korean
      American adolescents. It was hypothesized that personal spirituality and
      mentoring relationship quality would mediate the relation between church
      engagement and adolescent outcomes. Data were obtained through a self-report
      survey from 248 Korean American adolescents in grades 7 through 12. High levels
      of church engagement, as characterized by years of attendance, choice to attend,
      and participation in activities, predicted deeper personal spirituality and
      better mentoring relationships. Personal spirituality, as measured by one's daily
      religious experiences, beliefs, and private spiritual practices, was a mediator
      of the relationship between church engagement and adolescent outcomes.
      Specifically, higher levels of church engagement was linked to stronger personal
      spirituality, which in turn predicted less depressive symptoms for girls and
      higher grades for boys.

PMID- 20813403
TI  - The protective activities of water-soluble C(60) derivatives against nitric oxide
      induced cytotoxicity in rat pheochromocytoma cells.
AB  - In this study, the protective activities of water-soluble C(60) derivatives
      against nitric oxide (NO) induced cytotoxicity were investigated. To overcome
      C(60) insolubility in water, we modified C(60) with beta-alanine, valine or
      folacin. The compounds were characterized by FT-IR, (1)H NMR, (13)C NMR, LC-MS,
      elemental analysis, light scattering and TEM. Investigation of the possible NO
      scavenging activities of water-soluble C(60) derivatives demonstrated that they
      expressed direct scavenging activity toward NO liberated within solution of
      sodium nitroprusside (SNP). In parallel, following exposure of cells to SNP (1
      mM), a marked decrease in mitochondrial membrane potential, cell viability,
      activities of superoxide dismutase (SOD), catalase (CAT) and glutathione
      peroxidase (GSH-Px), as well as increased levels of intracellular NO accumulation
      and malondialdehyde (MDA) production were observed. Moreover, SNP caused
      significant elevation in intracellular caspase-3 activity, and induced apoptotic
      death as determined by flow cytometric assay. However, pretreatment of the cells
      with water-soluble C(60) derivatives prior to SNP exposure blocked these NO
      induced cellular events noticeably. Experiments demonstrated that the aggregation
      morphology could impact the NO-scavenging abilities and protective effects on
      apoptosis of water-soluble C(60) derivatives. The results suggest that water
      soluble C(60) derivatives have the potential to prevent NO-mediated cell death
      without evident toxicity.

PMID- 20813404
TI  - Multiplexed supramolecular self-assembly for non-viral gene delivery.
AB  - Recently, there has been success in applying a semi-rational approach to non
      viral gene delivery vector development using a combinatorial/parallel synthesis
      approach to construct libraries of materials with unique molecular structures. In
      this approach, it is hoped that the random incorporation of various hydrophobic
      and hydrophilic domains in the library will yield candidates with the appropriate
      balance of DNA binding strength and endosomolytic properties to yield efficient
      gene delivery. Herein we describe a library approach to gene delivery vector
      development that relies on the supramolecular self-assembly of individual
      components instead of chemical reaction. Each component in the described system
      is capable of performing a single and well-defined purpose--DNA binding
      (dioleylspermine), membrane permeation (oligoarginine) or targeting (folic acid).
      A combination of electrostatic attraction and the hydrophobic effect is used to
      bring the individual groups together to form nanoscale complexes with DNA.
      Because the components responsible for DNA binding, membrane permeation and
      targeting are separate, it is possible to alter the balance between hydrophilic
      and hydrophobic groups by varying the relative amounts in the final formulation.
      By doing so, we can readily identify cell-specific formulations that have greater
      transfection efficiency than the individual components and have superior
      transfection efficiency to lipofectamine 2000 under similar conditions.

PMID- 20813405
TI  - Ionic complex systems based on hyaluronic acid and PEGylated TNF-related
      apoptosis-inducing ligand for treatment of rheumatoid arthritis.
AB  - The clinical applications of tumor necrosis factor (TNF)-related apoptosis
      inducing ligand (TRAIL), an emerging therapeutic protein for cancer and
      rheumatoid arthritis (RA), are limited by its instability and short biological
      half-life. In this study, efficient therapeutic modalities for RA treatment were
      developed in the form of nano-sized complexes (nanocomplexes) based on hyaluronic
      acid (HA) and polyethylene glycol (PEG)-derivatized TRAIL (PEG-TRAIL) formed by N
      terminal specific PEGylation. The nanocomplexes were prepared by simply mixing
      the positively charged PEG-TRAIL and negatively charged HA, and showed negligible
      loss of bioactivity compared with the PEG-TRAIL. The in vivo biodistribution and
      diffusion kinetics of Cy5.5-labeled PEG-TRAIL in mice were observed using a near
      infrared optical imaging system after subcutaneous injection of three different
      formulations: PEG-TRAIL in phosphate-buffered saline (PBS, pH 7.4), nanocomplex
      in PBS, or nanocomplex in 1% HA solution. The results suggested that PEG-TRAIL is
      released slowly in vivo from the nanocomplex in 1% HA. Experiments in a collagen
      induced arthritis mouse model demonstrated that the magnitudes of therapeutic
      effects, as judged by clinical scores and histology, were significantly enhanced
      by the sustained delivery of PEG-TRAIL, with the order of nanocomplex in 1%
      HA>nanocomplex in PBS>PEG-TRAIL in PBS. In addition, sustained delivery of PEG
      TRAIL from the nanocomplex in 1% HA resulted in significant reduction of serum
      inflammatory cytokines and collagen-specific antibodies that are responsible for
      the pathogenesis of RA. These results imply that HA/PEG-TRAIL nanocomplex
      formulations are promising therapeutic modalities for the treatment of RA.

PMID- 20813406
TI  - Manganese effects in the liver following subacute or subchronic manganese
      chloride exposure in rats.
AB  - Manganese (Mn) toxicity is most often found in mining and welding industry
      workers. Accumulation of manganese in the brain can result in a syndrome similar
      to that of Parkinson's disease. Observations on former Mn-alloy workers suggested
      that residual effects could last for years after exposure. The objective of this
      study was to assess effects of Mn in the liver of rats following subacute or
      subchronic exposure and after recovery. Male Sprague-Dawley rats were exposed to
      manganese chloride (MnCl(2)) for 30 days, 90 days, or for 90 days followed by a
      30-day post-exposure recovery period. Results showed that MnCl(2) exposure
      resulted in liver injury in rats and the extent of injury correlated positively
      with exposure time. The effect in mitochondria was stronger than in the membrane
      or nucleus. Most of the changes in these biomarkers recovered when manganese
      exposure ceased.

PMID- 20813407
TI  - A comparison of metal levels and antioxidant enzymes in freshwater snails,
      Lymnaea natalensis, exposed to sediment and water collected from Wright Dam and
      Lower Mguza Dam, Bulawayo, Zimbabwe.
AB  - We compared the bioaccumulation of lead (Pb), cadmium (Cd), zinc (Zn), copper
      (Cu), nickel (Ni) and iron (Fe) with antioxidant enzyme activity in tissues of
      the snails, Lymnaea natalensis, exposed to elements of two differently polluted
      dams. 45 snails were exposed to sediment and water collected from Wight Dam
      (reference) whilst another 45 snails were also exposed to sediment and water
      collected from Lower Mguza Dam (polluted dam). Except for Fe in sediment and Pb
      in water, metal concentrations were statistically higher in sediment and water
      collected from Lower Mguza Dam. Lead, Cd and Zn were two times higher in tissues
      of snails exposed to Lower Mguza Dam elements. On one hand, superoxide dismutase
      (SOD), diphosphotriphosphodiaphorase (DTD) and catalase (CAT) activities were
      significantly lower whilst malondialdehyde (MDA) levels were significantly higher
      in tissues of snails exposed to Lower Mguza Dam sediment and water. On the other
      hand, selenium-dependent glutathione peroxidase (Se-GPX) activity was
      significantly elevated in tissues of snails exposed to Lower Mguza Dam sediment
      and water. Snails exposed to Lower Mguza Dam elements seem to have responded to
      pollution by increasing CAT and Se-GPX specific activity in an effort to detoxify
      peroxides produced as a result of metal induced oxidative stress.

PMID- 20813408
TI  - The toxicity of Roundup(r) 360 SL formulation and its main constituents:
      glyphosate and isopropylamine towards non-target water photoautotrophs.
AB  - The toxicity of commercial formulation of Roundup(r) 360 SL, widely used,
      nonselective herbicide and its main constituents, glyphosate (PMG), equimolar
      (1:1) isopropylamine salt of glyphosate (GIPA) and isopropylamine (IPA) was
      examined towards eight aquatic microphotoautotrophs; seven cyanobacterial strains
      representing either saline or freshwater communities, and common eukaryotic algae
      Chlorella vulgaris Beijerinck. Autotrophs were cultured 21 days in their
      appropriate standard media supplemented with various amounts of Roundup(r),
      glyphosate, GIPA and IPA. The determination of the growth of examined
      photoautotrophs was performed by time-course measurements of total chlorophyll
      content in experimental cultures. The growth rates related to corresponding
      concentrations of chemicals, the EC(50) values and generation doubling time were
      determined in order to present the toxicity Roundup(r) 360 SL formulation and its
      main constituents. Market available formulation of Roundup(r) was found to
      possess toxicity significantly higher than this, attributed to its main
      constituents; however both these compounds, isopropylamine and glyphosate, also
      inhibited the growth of examined strains in a dose-dependent manner. Notably, the
      interpretation of toxicity of the examined substances was found to be
      significantly dependent on the method of EC(50) calculation. The choice of molar
      or weight concentration of substances tested separately and in specific
      formulation was found to be essential in this matter. Due to these findings the
      EC(50) values were calculated based either on molar or on weight concentrations.
      Considering Roundup(r) 360 SL formulation, these values ranged from 10(-3) up to
      10(-1) mM and they were one order of magnitude lower than those found for
      isopropylamine. Quite surprisingly the minimum EC(50) values found for glyphosate
      did not reach micromolar concentrations, whereas most of the EC(50) values
      revealed to IPA did not exceed this range. Notably, in all the cases except for
      Synechocystis aquatilis Sauvageau, isopropylamine alone was indicated as more
      toxic than glyphosate.

PMID- 20813409
TI  - CNS-specific expression of C3a and C5a exacerbate demyelination severity in the
      cuprizone model.
AB  - Demyelination in the central nervous system (CNS) is known to involve several
      immune effector mechanisms, including complement proteins. Local production of
      complement by glial cells in the brain can be both harmful and protective. To
      investigate the roles of C3a and C5a in demyelination and remyelination pathology
      we utilized the cuprizone model. Transgenic mice expressing C3a or C5a under the
      control of the glial fibrillary acidic protein (GFAP) promoter had exacerbated
      demyelination and slightly delayed remyelination in the corpus callosum compared
      to WT mice. C3a and C5a transgenic mice had increased cellularity in the corpus
      callosum due to increase activation and/or migration of microglia.
      Oligodendrocytes migrated to the corpus callosum in higher numbers during early
      remyelination events in C3a and C5a transgenic mice, thus enabling these mice to
      remyelinate as effectively as WT mice by the end of the 10 week study. To
      determine the effects of C3a and/or C5a on individual glial subsets, we created
      murine recombinant C3a and C5a proteins. When microglia and mixed glial cultures
      were stimulated with C3a and/or C5a, we observed an increase in the production of
      proinflammatory cytokines and chemokines. In contrast, astrocytes had decreased
      cytokine and chemokine production in the presence of C3a and/or C5a. We also
      found that the MAPK pathway proteins JNK and ERK1/2 were activated in glia upon
      stimulation with C3a and C5a. Overall, our findings show that although C3a and
      C5a production in the brain play a negative role during demyelination, these
      proteins may aid in remyelination.

PMID- 20813411
TI  - Moscow eye microsurgery complex in Russia keratoprosthesis in Beijing.
AB  - PURPOSE: To evaluate the efficacy and preliminary safety of the Moscow Eye
      Microsurgery Complex in Russia (MICOF) keratoprosthesis in eyes with complicated
      corneal opacities unsuitable for keratoplasty. DESIGN: Retrospective review of
      consecutive clinical case series. PARTICIPANTS: We analyzed 85 eyes of 85
      patients who previously underwent MICOF keratoprosthesis implantation at the
      Chinese PLA General Hospital between April 1, 2000, and August 31, 2009. The mean
      follow-up after MICOF keratoprosthesis implantation (measured after the second
      stage of the implantation) was 34.7 months (range, 3-107 months). METHODS: The
      MICOF keratoprosthesis surgery involves 2 procedures. In stage 1, a supporting
      titanium frame is inserted into the lamellar pocket; a polymethyl methacrylate
      (PMMA) optical cylinder is implanted 3 months later (stage 2). Data were
      collected from the preoperative, intraoperative, and postoperative courses.
      Statistical analysis was performed to identify factors influencing postoperative
      complications. MAIN OUTCOME MEASURES: Visual acuity (VA), keratoprosthesis
      retention, and significant postoperative complications. RESULTS: The MICOF
      keratoprosthesis dramatically improved vision in most patients. The percentage of
      eyes with postoperative VA of 20/100 or better was 80.7% (67/83) at 6 months
      after stage 2, 82.4% (61/74) at 1 year, 72.7% (40/55) at 2 years, 78.8% (26/33)
      at 3 years, 78.9% (15/19) at 4 years, 100% (8/8) at 5 years, 80% (4/5) at 6
      years, 100% (2/2) at 7 and 8 years, and 100% (1/1) at 9 years. The most common
      complication, retroprosthetic membrane formation, occurred in 39 of 85 eyes. The
      overall keratoprosthesis retention rate was 81.2% at an average follow-up of 34.7
      months (range, 3-107 months). Ten eyes presented with elevated intraocular
      pressure after implantation; 3 of these had underlying glaucoma. All 3 eyes
      received cyclocryotherapy to control intraocular pressure. Sterile vitreitis
      occurred in 2 eyes, and retinal detachment occurred in 1 eye. CONCLUSIONS: The
      MICOF keratoprosthesis is an effective alternative for patients with corneal
      blindness and a poor prognosis for penetrating keratoplasty.

PMID- 20813410
TI  - Plaque radiotherapy for juxtapapillary choroidal melanoma: tumor control in 650
      consecutive cases.
AB  - PURPOSE: To evaluate treatment of juxtapapillary choroidal melanoma with plaque
      radiotherapy and to investigate the role of supplemental transpupillary
      thermotherapy (TTT). DESIGN: Retrospective, comparative case series.
      PARTICIPANTS: We included 650 consecutive eyes with juxtapapillary choroidal
      melanoma within 1 mm of the optic disc. METHODS: Eyes with juxtapapillary
      choroidal melanoma receiving plaque radiotherapy over a 31-year period from
      October 1974 to November 2005 were included in the study. The TTT and no TTT
      groups were analyzed separately and compared. MAIN OUTCOME MEASURES: Local tumor
      control, metastasis, and tumor-related mortality. RESULTS: The median basal tumor
      diameter was 10 mm (range, 1.5-21) and median thickness was 3.5 mm (range, 0.5
      14.8). In 481 eyes (74%), the tumor was directly adjacent to the optic disc and
      in 169 eyes (26%) the posterior tumor margin was between 0.1 and 1.0 mm from the
      optic disc. The circumpapillary extent of the tumor was <4 clock-hours in 321
      eyes (50%), 4-8 clock-hours in 250 eyes (38%), and >8 clock-hours in 79 eyes
      (12%). Plaque radiotherapy using iodine-125 in 616 eyes (95%), cobalt-60 in 19
      eyes (3%), iridium-192 in 12 eyes (2%), and ruthenium-106 in 3 eyes (<1%)
      delivered a median radiation dose of 8000 cGy (range, 3600-15 500) to the tumor
      apex and adjunctive TTT was used in 307 eyes (56%). Kaplan-Meier estimates for
      tumor recurrence, metastasis, and death were 14%, 11%, and 4% at 5 years and 21%,
      24%, and 9% at 10 years, respectively. Eyes treated with additional TTT showed
      slight (statistically nonsignificant) reduction in recurrence and metastasis.
      Using multivariable analysis, factors predictive of tumor recurrence included
      foveolar tumor requiring TTT (hazard ratio, 5.07; P<0.001) and greater tumor
      thickness (hazard ratio, 1.29 per mm increase; P<0.001). Factors predictive of
      metastasis included greater tumor base (hazard ratio, 1.21 per mm increase;
      P<0.001) and increasing intraocular pressure (hazard ratio, 1.11 per mmHg
      increase; P = 0.020). CONCLUSIONS: Plaque radiotherapy for juxtapapillary
      melanoma provides local tumor control in approximately 80% of eyes at 10 years.
      In subjects who received TTT, there was slight but nonsignificant improved local
      tumor control and lower metastatic rate.

PMID- 20813413
TI  - No association between schizophrenia and rs27388 of the MEGF10 gene in Chinese
      case-control sample.

PMID- 20813412
TI  - Cannabis users differ from non-users on measures of personality and schizotypy.
AB  - Accumulating evidence indicates that cannabis use may be a risk factor for
      schizophrenia (SZ), and chronic cannabis users score higher than non-users on
      measures of schizotypal personality traits. The purpose of the present study was
      to investigate the relations between normal personality, schizotypy, and cannabis
      use. Sixty-two chronic cannabis users and 45 cannabis-naive controls completed a
      measure of normal personality, the NEO-Five Factor Inventory (NEO-FFI), and two
      measures of schizotypy, the schizotypal personality questionnaire (SPQ) and
      perceptual aberration scale (PAS). Substance use was assessed using the SCID I
      alcohol/drug module and a locally developed drug use questionnaire. On the NEO
      FFI, users scored higher than controls on openness, but lower on agreeableness
      and conscientiousness, and endorsed greater schizotypy on the SPQ and PAS. Higher
      neuroticism predicted greater schizotypy in both groups, and, higher Extraversion
      predicted lower negative-syndrome schizotypy among users. Finally, duration of
      cannabis use was positively correlated with scores on the SPQ and PAS among
      users, suggesting a relation between overall cannabis use chronicity and
      schizotypy. These data show that cannabis users differ from non-users on
      dimensions of normal personality and schizotypy, and provide further evidence
      that cannabis use is associated with increased levels of psychosis-related
      personality traits.

PMID- 20813414
TI  - Cortisol reactivity in boys with attention-deficit/hyperactivity disorder and
      disruptive behavior problems: the impact of callous unemotional traits.
AB  - There is a body of literature demonstrating an association between altered
      hypothalamic pituitary adrenal (HPA) axis reactivity and aggressive behavior.
      Aggressive and disruptive behavior also is highly prevalent in children with
      attention deficit/hyperactivity disorder (ADHD). Findings on HPA-axis reactivity
      in ADHD, however, are rather inconsistent. Specific temperamental risk factors
      previously were associated with a specific subtype of severe disruptive behavior.
      These traits might also be characterized by a distinct neurobiological profile
      across ADHD and disruptive behavior disorders. In this study we focus on
      psychopathic traits, notably callous unemotional (CU) traits. The main objective
      of the present study was to investigate whether two groups of ADHD patients with
      high or low CU traits differed in cortisol reactivity. Subjects were 36 boys with
      ADHD and disruptive behavior symptoms aged 8 to 14 years. Salivary cortisol
      probes were taken before and repeatedly after an experimental standardized stress
      test. Patients scoring high on CU traits showed a blunted HPA axis reactivity to
      the experimentally induced stress. Results underscore the need to consider
      specific personality traits in investigating neurobiological correlates in ADHD
      with disruptive behavior problems.

PMID- 20813415
TI  - Qualitative and quantitative evidence of anti-glutamic acid decarboxylase
      specific intrathecal antibody synthesis in patients with stiff person syndrome.
AB  - BACKGROUND: The stiff person syndrome (SPS) is a CNS disorder of putative
      autoimmune aetiology, which is clinically characterized by severe rigidity and
      spasms. In most cases, SPS is associated with serum antibodies against glutamic
      acid decarboxylase (GAD-Ab). Recent studies suggested that GAD-Ab might be
      directly involved in the pathogenesis of SPS. Further support for this hypothesis
      would come from studies providing qualitative evidence for the presence of GAD-Ab
      producing B cell clones within the CNS of patients with SPS. OBJECTIVE AND
      METHODS: To address that issue, we (i) analysed paired cerebrospinal fluid (CSF)
      and serum samples from ten GAD-Ab positive patients with SPS and controls by an
      antigen-driven affinity blotting technique for the presence of GAD-specific
      oligoclonal IgG bands (OCBs) in the CSF, and (ii) examined the immunoreactive
      pattern of CSF and serum IgG to recombinant GAD by immunoblotting. To confirm our
      results quantitatively, we (iii) assessed anti-GAD antibody reactivity in CSF and
      serum using ELISA and evaluated the GAD-specific antibody index. RESULTS: GAD
      specific oligoclonal bands exclusively or predominately in CSF compared to the
      corresponding serum were detected in 10/10 patients with GAD-positive SPS but in
      none of the controls. Immunoblotting revealed stronger staining in the CSF,
      suggestive of intrathecal IgG synthesis, in 7/10 patients upon visual inspection,
      and in 8/10 patients upon densitometric analysis. A positive GAD-specific
      antibody index was found in 9/10 patients. CONCLUSIONS: Here we demonstrate for
      the first time that IgG OCBs in SPS bind GAD. Our findings contribute to the
      ongoing discussion on whether the autoimmune process against GAD is involved in
      the pathogenesis of SPS by indicating that anti-GAD-Ab is produced by B cell
      clones within the CNS.

PMID- 20813416
TI  - Sex and age specific time patterns and long term time trends of pre-hospital
      delay of patients presenting with acute ST-segment elevation myocardial
      infarction.
AB  - BACKGROUND: Prompt initiation of treatment after symptom onset of ST-elevation
      myocardial infarction (STEMI) is a central goal in limiting myocardial damage
      because of the time-dependent nature of reperfusion therapies. We examined time
      patterns and long term time trends of pre-hospital delay time (PHDT) of STEMI
      patients. METHODS: PHDT from 3093 STEMI patients derived from the Augsburg
      Myocardial Infarction Registry (1985-2004) surviving >24h after admission was
      obtained by a standardized bedside interview. Patients with in-hospital MI
      (n=140) and resuscitation (n=157) were excluded. Linear regression models were
      used to examine monthly median PHDT and individual PHDT over time. RESULTS:
      Female sex was associated with longer PHDT (189 (98-542quartiles) min vs. 154 (85
      497) min; p<0.0003). Median PHDT in the youngest male subgroup (25-54 years) was
      128 (73-458) min and mounted to 205 (107-600) min in the oldest female subgroup
      (65-74 years). A minority of 12.4% of patients reached hospital within 1h of
      delay ranging from 8.7% (in oldest women) to 15.9% (in youngest men). The age
      adjusted linear regression model for monthly PHDT revealed no significant change
      over 20-year time in both sexes. The corresponding average annual percentage
      change estimates were -0.45 (95% CI: -1.40 to 0.54) for men and -0.08 (95% CI: 
      1.80 to 1.67) for women. Emergency ambulance use increased over time, however
      transportation time remained stable. CONCLUSIONS: PHDT in STEMI patients is
      constantly high over a 20-year observation period. Room for improvement
      especially in older women was evidenced. Preventive strategies with focused
      efforts on this subgroup are warranted.

PMID- 20813417
TI  - Tuning of human vestibulospinal reflexes by leg rotation.
AB  - Changing the foot position modifies the mechanical action exerted by the ankle
      extensor and flexor muscles over the body. We verified, in two groups of healthy
      subjects standing with the heels touching or apart, whether a 90 degrees 
      external rotation of the right leg and foot also changes the pattern of
      vestibulospinal reflexes elicited by electrical stimulation of the labyrinth.
      With the head oriented forward, leg rotation did not modify the labyrinthine
      driven displacements of the center of pressure (CoP). When the head was rotated
      in the horizontal plane, either to the right or to the left, the CoP displacement
      increased along the y axis in all subjects. Changes in the x component in most
      instances appropriate to preserve unmodified the direction of body sway elicited
      by the stimulus were observed. Right leg rotation increased the basal EMG
      activity of ankle extensors and flexors on the left side, while the right side
      activity was unaffected. The EMG responses to labyrinthine stimulation were
      modified only on the left side, in a way appropriate to correct the effects of
      the altered torque pattern exerted on the body by right leg muscles. It appears,
      therefore, that somatosensory signals related to leg rotation and/or copy of the
      corresponding voluntary motor commands modify the pattern of vestibulospinal
      reflexes and maintain the postural response appropriate to counteract a body sway
      in the direction inferred by labyrinthine signals.

PMID- 20813418
TI  - Soluble TNF, but not membrane TNF, is critical in LPS-induced hepatitis.
AB  - BACKGROUND & AIMS: : Bacillus Calmette-Guerin (BCG) infection causes hepatic
      injury following granuloma formation and secretion of cytokines which renders
      mice highly sensitive to endotoxin-mediated hepatotoxicity. Tumor necrosis factor
      (TNF) is required for granuloma formation and is one of the most important
      cytokines in liver injury. TNF inhibitors are effective therapies for
      inflammatory diseases. However, clinical use of non-selective TNF inhibitors is
      associated with an increased risk of infections. This work investigates the
      differential roles of soluble TNF (solTNF) and membrane TNF (memTNF) in BCG
      infection, BCG/LPS- and D-GALN/LPS-induced liver injury. METHODS: We have used
      both genetic and pharmacologic approaches and analyzed liver injury, TLR4,
      cytokine and iNOS activation induced by BCG, BCG/LPS and D-GALN/LPS. RESULTS: BCG
      infection-induced liver injury is seen in wild-type mice but not in TNF(-/-),
      memTNF knock-in (KI), and sTNFR1-Fc transgenic mice. Severity of BCG-induced
      liver injury is correlated with BCG-granuloma number and hepatic expression of
      TLR4 and iNOS. In addition, protection from liver damage caused by BCG/LPS or D
      GALN/LPS administration was observed in TNF(-/-), memTNF KI and sTNFR1-Fc
      transgenic mice. To extend the genetic findings, we then evaluated whether
      selective pharmacological inhibition of solTNF by dominant-negative (DN)-TNF
      neutralization and non-selective inhibition of solTNF and memTNF by anti-TNF
      antibodies and etanercept (TNFR2-IgG1) can protect the mice from liver injury.
      Both selective and non-selective inhibition of solTNF protected mice from BCG/LPS
      and D-GALN/LPS-induced liver damage. CONCLUSIONS: These data suggest that memTNF
      is not mediating liver injury and that selective inhibition of solTNF sparing
      memTNF may represent a new therapeutic strategy to treat immune-mediated
      inflammatory liver diseases.

PMID- 20813419
TI  - Iron inhibits replication of infectious hepatitis C virus in permissive Huh7.5.1
      cells.
AB  - BACKGROUND & AIMS: Chronic infection with hepatitis C virus (HCV) is often
      associated with elevated hepatic iron levels. Excess iron is known to promote
      oxidative stress and exacerbate liver disease. Nevertheless, biochemical studies
      in subgenomic HCV replicon systems showed that iron can also suppress the
      expression of viral RNA and proteins by inhibiting the enzymatic activity of the
      RNA polymerase NS5B. To explore the physiological relevance of this response, we
      evaluated the effects of iron during infection of permissive Huh7.5.1 hepatoma
      cells with HCV. METHODS: We utilized Fe-SIH (iron complexed with salicylaldehyde
      isonicotinoyl hydrazone), a cell permeable and highly efficient iron donor.
      RESULTS: Treatments of infected cells with Fe-SIH drastically reduced the
      expression of viral proteins (core and NS3) and RNA, in a dose-dependent manner.
      The inhibition was dramatic when Fe-SIH was administered simultaneously with the
      HCV inoculum or early afterwards, while pre-treatment of cells with Fe-SIH before
      infection failed to elicit antiviral responses. Iron chelation with SIH did not
      significantly alter the expression of viral proteins. CONCLUSIONS: Our data
      establish a critical role of hepatic iron concentration on the progression of HCV
      infection, and are consistent with iron-mediated inactivation of NS5B.

PMID- 20813420
TI  - Health span or life span: the role of patient-reported outcomes in informing
      health policy.
AB  - OBJECTIVES: Population ageing and the increasing burden of chronic conditions
      challenge traditional metrics of assessing the efficacy of health care
      interventions and as a consequence policy and planning. Using chronic heart
      failure (CHF) as an exemplar this manuscript seeks to describe the importance of
      patient-reported outcomes to inform policy decisions. METHODS: The method of an
      integrative review has been used to identify patient-reported outcomes (PROs) in
      assessing CHF outcomes. Using the Innovative Care for Chronic Conditions the case
      for developing a metric to incorporate PROs in policy planning, implementation
      and evaluation is made. RESULTS: In spite of the increasing use of PROs in
      assessing CHF outcomes, their incorporation in the policy domain is limited.
      CONCLUSIONS: Effective policy and planning is of health care services is
      dependent on the impact on the individual and their families. Epidemiological
      transitions and evolving treatment paradigms challenge traditional metrics of
      morbidity and mortality underscoring the importance of assessing PROs.

PMID- 20813421
TI  - Towards a complete resolution of the genetic architecture of disease.
AB  - After years of linear gains in the genetic dissection of human disease we are now
      in a period of exponential discovery. This is particularly apparent for complex
      disease. Genome-wide association studies (GWAS) have provided myriad associations
      between common variability and disease, and have shown that common genetic
      variability is unlikely to explain the entire genetic predisposition to disease.
      Here we detail how one can expand on this success and systematically identify
      genetic risks that lead or predispose to disease using next-generation
      sequencing. Geneticists have had for many years a protocol to identify Mendelian
      disease. A similar set of tools is now available for the identification of rare
      moderate-risk loci and common low-risk variants. Whereas major challenges
      undoubtedly remain, particularly regarding data handling and the functional
      classification of variants, we suggest that these will be largely practical and
      not conceptual.

PMID- 20813422
TI  - Indistinguishability and identifiability of kinetic models for the MurC reaction
      in peptidoglycan biosynthesis.
AB  - An important question in Systems Biology is the design of experiments that enable
      discrimination between two (or more) competing chemical pathway models or
      biological mechanisms. In this paper analysis is performed between two different
      models describing the kinetic mechanism of a three-substrate three-product
      reaction, namely the MurC reaction in the cytoplasmic phase of peptidoglycan
      biosynthesis. One model involves ordered substrate binding and ordered release of
      the three products; the competing model also assumes ordered substrate binding,
      but with fast release of the three products. The two versions are shown to be
      distinguishable; however, if standard quasi-steady-state assumptions are made
      distinguishability cannot be determined. Once model structure uniqueness is
      ensured the experimenter must determine if it is possible to successfully recover
      rate constant values given the experiment observations, a process known as
      structural identifiability. Structural identifiability analysis is carried out
      for both models to determine which of the unknown reaction parameters can be
      determined uniquely, or otherwise, from the ideal system outputs. This structural
      analysis forms an integrated step towards the modelling of the full pathway of
      the cytoplasmic phase of peptidoglycan biosynthesis.

PMID- 20813423
TI  - Bronchoscopic microsampling is a useful complementary diagnostic tool for
      detecting lung cancer.
AB  - PURPOSE: Bronchoscopic microsampling (BMS) is a novel and direct method with
      which to obtain epithelial lining fluid (ELF) from the lungs. Analysis of DNA
      hypermethylation of tumor suppressor genes (TSGs) is expected to be a sensitive
      tool for the early detection of lung cancer. It has been reported that the
      existence of EGFR mutations and EML4-ALK gene rearrangements are related to the
      sensitivity of corresponding kinase inhibitors. We aimed to evaluate the
      suitability of ELF as a sample for analyzing molecular changes specific for lung
      cancer. PATIENTS AND METHODS: We collected ELF from 61 lung cancer patients by
      BMS from the airway close to the peripheral lung nodule and purified the nucleic
      acids. We performed methylation specific PCR in each ELF as well as matched serum
      and tumor tissue for TSGs for DNA methylation analysis. We also examined EGFR
      mutations and EML4-ALK rearrangement. RESULTS: The sensitivity for detecting DNA
      hypermethylation in ELF vs serum was 74.1% vs 18.5%. We found 60.1% of patients
      had at least one hypermethylation in ELF, while only 27.9% had it in serum. Of
      note, DNA hypermethylation was detected even in stage I patients (60.0%) and the
      detection rate was almost the same level in each stage. We also found the
      sensitivity for detecting EGFR mutation in ELF vs serum was 58.3% vs 8.3%. We
      detected an EML4-ALK fusion gene using ELF in one patient. CONCLUSIONS: BMS is an
      alternative method to detect cancer specific genetic and epigenetic alterations
      and will be a useful complementary diagnostic tool for lung cancer. SUMMARY:
      Investigation of genetic and epigenetic changes associated with lung cancer has
      clinical importance for its diagnosis and management. The clinical usefulness of
      bronchoscopic microsampling (BMS) in lung cancer has not yet been evaluated. This
      study demonstrates that BMS could be useful for detecting lung cancer specific
      molecular changes and valuable for early diagnosis and determination of treatment
      options for lung cancer.

PMID- 20813424
TI  - Biodiversity "surpluses" and "deficits" are not novel issues.

PMID- 20813425
TI  - Multi-decadal oceanic ecological datasets and their application in marine policy
      and management.
AB  - Long-term biological time-series in the oceans are relatively rare. Using the two
      longest of these we show how the information value of such ecological time-series
      increases through space and time in terms of their potential policy value. We
      also explore the co-evolution of these oceanic biological time-series with
      changing marine management drivers. Lessons learnt from reviewing these sequences
      of observations provide valuable context for the continuation of existing time
      series and perspective for the initiation of new time-series in response to rapid
      global change. Concluding sections call for a more integrated approach to marine
      observation systems and highlight the future role of ocean observations in
      adaptive marine management.

PMID- 20813426
TI  - Environmental benefits and risks of zero-valent iron nanoparticles (nZVI) for in
      situ remediation: risk mitigation or trade-off?
AB  - The use of nanoscaled zero-valent iron particles (nZVI) to remediate contaminated
      soil and groundwater has received increasing amounts of attention within the last
      decade, primarily due to its potential for broader application, higher
      reactivity, and cost-effectiveness compared to conventional zero-valent iron
      applications and other in situ methods. However, the potential environmental
      risks of nZVI in in situ field scale applications are largely unknown at the
      present and traditional environmental risk assessment approaches are not yet able
      to be completed. Therefore, it may not yet be fully clear how to consider the
      environmental benefits and risks of nZVI for in situ applications. This analysis
      therefore addresses the challenges of comprehensively considering and weighing
      the expected environmental benefits and potential risks of this emerging
      environmentally-beneficial nanotechnology, particularly relevant for
      environmental engineers, scientists, and decision makers. We find that most of
      the benefits of using nZVI are based on near-term considerations, and large data
      gaps currently exist within almost all aspects of environmental exposure and
      effect assessments. We also find that while a wide range of decision support
      tools and frameworks alternative to risk assessment are currently available, a
      thorough evaluation of these should be undertaken in the near future to assess
      their full relevancy for nZVI at specific sites. Due to the absence of data in
      environmental risk evaluations, we apply a 'best' and 'worst' case scenario
      evaluation as a first step to qualitatively evaluate the current state-of
      knowledge regarding the potential environmental risks of nZVI. The result of this
      preliminary qualitative evaluation indicates that at present, there are no
      significant grounds on which to form the basis that nZVI currently poses a
      significant, apparent risk to the environment, although the majority of the most
      serious criteria (i.e. potential for persistency, bioaccumulation, toxicity) are
      generally unknown. We recommend that in cases where nZVI may be chosen as the
      'best' treatment option, short and long-term environmental monitoring is actively
      employed at these sites. We furthermore recommend the continued development of
      responsible nZVI innovation and better facilitated information exchange between
      nZVI developers, nano-risk researchers, remediation industry, and decision
      makers.

PMID- 20813427
TI  - Transparent peer review--an appreciation of the reviewers' contribution to a
      published article.

PMID- 20813428
TI  - Involvement of anion channels in mediating elicitor-induced ATP efflux in Salvia
      miltiorrhiza hairy roots.
AB  - This study examines the roles of anion channels and ATP binding cassette (ABC)
      protein transporters in mediating elicitor-induced ATP release in Salvia
      miltiorrhiza hairy root cultures. The elicitor-induced ATP release was
      effectively blocked by two putative membrane anion channel blockers, niflumic
      acid and Zn(2+), but not by a specific Cl(-) channel blocker, phenylanthranilic
      acid. The elicitor-induced ATP release was also significantly suppressed by two
      ABC inhibitors, glibenclamide and ethacrynic acid. Notable ATP release from the
      hairy roots was also induced by verapamil (2mM), an ABC activator in animal
      cells. The verapamil-induced ATP release was effectively blocked by niflumic
      acid, but only slightly inhibited by the ABC inhibitors. Another notable effect
      of verapamil was the induction of exocytosis, the secretion of vesicle-like
      particles to the root surface. The verapamil-induced exocytosis was not inhibited
      by nifulumic acid and YE did not induce the exocytosis. Overall, the results
      suggest a significant role of anion channels, a possible involvement of ABC
      proteins and no significant involvement of exocytosis in mediating the ATP efflux
      in hairy root cells.

PMID- 20813429
TI  - Synthesis and antimicrobial studies of thiazolotriazinones.
AB  - A series of 6-substituted phenyl thiazolo-1,2,4-triazinones (8) were obtained by
      the initial reaction of 6-substituted arylmethyl-3-mercapto-1,2,4-triazin-5-ones
      (5) with substituted phenacyl bromides (6) and further followed by PPA
      cyclization. The structures of the newly synthesized compounds were confirmed by
      IR, (1)H NMR, Mass and analytical data. Compounds 8a, 8e, 8f and 8h exhibited
      good antimicrobial activity.

PMID- 20813430
TI  - Homology modeling and molecular dynamics of CYP1A1 and CYP2B1 to explore the
      metabolism of aryl derivatives by docking and experimental assays.
AB  - Since many drugs are metabolized by cytochrome P450 (CYP450), biotransformation
      studies using these enzymes are valuable in drug development. In this work, the
      biotransformation by CYP1A1 and CYP2B1 of two acetylcholinesterase (AChE)
      inhibitors, 4-(4'-hydroxy-phenylamino)-4-oxo propanoic acid (A) and 1H
      pyrrolidine-1-(4'-hydroxy-phenyl)-2,5-dione (B), was investigated through docking
      and molecular dynamics (MD) simulations and by experimental methods using rat
      liver microsomes pretreated with beta-naphthoflavone and phenobarbital (CYP1A1
      and CYP2B1 inducers, respectively). The target proteins were initially built by
      homology modeling, and the resulting three-dimensional structures were refined by
      MD to obtain fifteen snapshots of each P450 isoform. These snapshots were used to
      dock compounds A and B as well as the reference compound acetaminophen (APAP). We
      confirmed that APAP produces a toxic intermediate (N-acetyl-p-benzoquinone imine)
      upon interaction of its amide group with the heme iron of CYP1A1. However,
      neither A nor B presented this kind of interaction within any snapshot with
      CYP1A1. On the other hand, when APAP, A and B were docked on CYP2B1, their
      hydroxyl group was located near the heme iron on the snapshot at 3.5 ns.
      Furthermore, B maintained the same position on all snapshots of this isoform.
      Therefore, theoretical results suggests that A and B do not generate toxic
      metabolites. These data were supported by HPLC analysis showing only one
      metabolite from A and B, which was identified by GC-MS as the hydroxylated
      product. Altogether, our results suggest that neither test compound is toxic.

PMID- 20813431
TI  - Synthesis and anti-inflammatory activity evaluation of some novel 6
      alkoxy(phenoxy)-[1,2,4]triazolo[3,4-a]phthalazine-3-amine derivatives.
AB  - Starting from phthalic anhydride, several new 6-alkoxy(phenoxy)
      [1,2,4]triazolo[3,4-a]phthalazine-3-amine derivatives were synthesized as potent
      anti-inflammatory agent. The study showed that the compounds 6h (6-(2
      chlorophenoxy)-[1,2,4]triazolo[3,4-a]phthalazine-3-amine) and 6s (6-(4
      aminophenoxy)-[1,2,4] triazolo[3,4-a]phthalazine-3-amine) exhibited the highest
      anti-inflammatory activity (81% and 83% inhibition, respectively, at 0.5 h after
      i.p. administration) which were slightly more potent than the reference drug
      Ibuprofen (61%). Furthermore, the peak activity of 6h and 6s was observed at the
      3 h after p.o. administration, and they exhibited stronger anti-inflammatory
      activity than Ibuprofen at the dose of 50 mg/kg at the peak time.

PMID- 20813432
TI  - Synthesis and anti-inflammatory activity of derivatives of coumarino-lignoid,
      cleomiscosin A and its methyl ether.
AB  - Six novel cleomiscosin A (a coumarino-lignoid), derivatives have been synthesized
      for the first time by using electrophilic substitution reaction to give nuclear
      nitrated and halogenated derivatives of cleomiscosin A in good yields. Structures
      of these compounds were established on the basis of IR, (1)H NMR, (13)C NMR and
      Mass spectral data. Some of the synthesized derivatives were tested for in-vitro
      target based anti-inflammatory study using primary macrophages cell culture
      bioassay system. The results showed that the compounds 1a, 3a and 4a (1 and 10
      MUg/mL) exhibited potent anti-inflammatory activity.

PMID- 20813433
TI  - Synthesis and antituberculosis activity of some new pyridazine derivatives. Part
      II.
AB  - A series of eighteen novel compounds with pyridazine moiety were synthesized and
      their in vitro antituberculosis activities have been evaluated. A fast, general,
      and facile method for preparation of pyridazine derivatives in moderate to
      excellent yields is presented. Three compounds were found to be moderate active
      against Mycobacterium tuberculosis. Correlation of structure-biological activity
      has been done.

PMID- 20813434
TI  - Antihypertensive activity of newer 1,4-dihydro-5-pyrimidine carboxamides:
      synthesis and pharmacological evaluation.
AB  - A number of 5-(4-substituted phenyl)-2-(substituted benzylsulfanyl)-4
      (substituted phenyl)-6-methyl-1,4-dihydro-5-pyrimidine carboxamides (1-30) were
      designed and synthesized keeping in view the structural requirements as suggested
      in the pharmacophore model for antihypertensive activity. All the synthesized
      compounds were tested for antihypertensive activity by non-invasive blood
      pressure (NIBP) measurements (tail-cuff method) in rats. Almost all the tested
      compounds displayed considerable decrease in the blood pressure as compared to
      control. Thirteen compounds showed significant antihypertensive activity
      comparable to the standard drug nifedipine.

PMID- 20813435
TI  - Synthesis and in vitro antiproliferative activity of 5-alkyl-12(H)-quino[3,4-b]
      [1,4]benzothiazinium salts.
AB  - A novel method of synthesizing 1,4-thiazine ring has led to the series of 5-alkyl
      12(H)-quino[3,4-b][1,4]benzothiazinium salts. The derivatives containing a butyl
      or decyl substituents on the quinoline nitrogen atom were obtained by alkylation
      of 12(H)-quino[3,4-b][1,4]benzothiazine with alkyl bromides. Antiproliferative
      activity in vitro of the compounds (3) was assessed using two cancer cell lines
      (Hct116 and LLC) and doxorubicin as a reference. Most of the studied
      phenothiazine derivatives showed activity against both cell lines investigated
      (2.2-19.6 MUg/mL concentration range). A structure-activity relationship was
      established. Only the compounds with substituents in the 11-position of the
      quinobenzothiazine ring did not exhibit activity against either cell line.

PMID- 20813436
TI  - Synthesis and antimicrobial activity of 2-substituted [4-(1,3,4-oxadiazol-2-yl
      methyl)] phthalazin-1(2H)-one derivatives.
AB  - A series of new 2-substituted [4-(1,3,4-oxadiazol-2-yl)methyl]phthalazin-1(2H)
      one derivatives 7a-h to 9a-h were designed and synthesized from methyl (4-oxo-3,4
      dihydrophthalazin-1-yl)acetate (4), which in was turn prepared from phthalic
      anhydride. The structure of synthesized new compounds were characterized by
      spectral data and screened for their antimicrobial activities against various
      bacteria and fungi strains. Several of these compounds showed antimicrobial
      activity.

PMID- 20813437
TI  - Synthesis of carbohydrate-conjugate heterobimetallic Cu(II)-Sn(2)(IV) and Zn(II)
      Sn(2)(IV) complexes; their interactions with CT DNA and nucleotides; DNA
      cleavage, in-vitro cytotoxicity.
AB  - The new heterobimetallic Ni(II)-Sn(2)(IV) (1), Cu(II)-Sn(2)(IV) (2) and Zn(II)
      Sn(2)(IV) (3) complexes, containing D-glucosamine, 1,8-diamino-3,6-diazaoctane
      and imidazole were isolated and characterized by spectral and analytical methods.
      The proposed geometry of Ni(II) and Cu(II) in 1 and 2 was square pyramidal,
      Zn(II) in 3 exhibited tetrahedral while Sn(IV) exhibits hexacoordinate
      environment, respectively. The X-ray powder diffraction (XRPD) confirmed the
      amorphous nature of all the complexes. The interaction studies of 2 and 3 with CT
      DNA were carried out by various biophysical techniques to show the mode of
      binding. The interaction of 2 and 3 with nucleotides viz 5'-GMP and 5'-TMP,
      respectively were further confirmed by (1)H, (31)P and (119)Sn NMR spectroscopy.
      The complex 2 exhibited effective cleavage activity with pBR322 DNA. Furthermore,
      the cytotoxicity of 2 was examined on a panel of human tumor cell lines of
      different histological origins and showed good activity against Colo205 and A2780
      (GI50 < 10 MUg/ml).

PMID- 20813438
TI  - Classification of drugs according to their milk/plasma concentration ratio.
AB  - The classification of drugs was done according to their milk/plasma concentration
      ratio (M/P) by using counter propagation artificial neural network (CP-ANN). The
      features of each drug were encoded by linear free energy relationship (LFER)
      parameters. These descriptors were used as inputs for developing linear
      discriminant analysis, quadratic discriminant analysis, least square support
      vector machine and CP-ANN models to distinguish the potential risk of 154 drugs
      as high risk (with M/P > 1) and low risk (with M/P < 1) for lactating women. The
      accuracy of classification for training, internal and external test sets was
      100.00%, 100.00% and 90.00%, respectively for CP-ANN model, as the best model.
      The obtained results revealed the applicability of CP-ANN in classification of
      drugs based on their M/P values, using LFER parameters.

PMID- 20813439
TI  - Employer-based support for registered nurses undertaking postgraduate study via
      distance education.
AB  - Previous literature has focused on the need for support of undergraduate nursing
      students during clinical placements. Little is known about the support provided
      by employers for registered nurses (RNs) who pursue further education. This study
      sought to identify and describe the types, levels and perceived need for support
      in the workplace for RNs as they undertake further postgraduate nursing study by
      distance education (DE). Using an exploratory descriptive design a self-report
      questionnaire was distributed to a convenient sample of 270 RNs working in one
      acute care public hospital in Tasmania, Australia. 92 questionnaires (response
      rate 34%) were returned with 26 (28%) reporting being currently enrolled in
      further study by DE and a further 50 (54)% of RNs planning future study. Results
      revealed that 100% of participants with a Masters degree completed this by DE.
      There were differences between the support sought by RNs to that offered by
      employers, and 16 (34%) who had done or were currently doing DE study, received
      no support to undertake DE. There was an overwhelming desire by RNs for support;
      87 (94%), with a majority believing some support should be mandatory 76 (83%).
      This study may encourage employers to introduce structured support systems that
      will actively assist nurses to pursue further study.

PMID- 20813440
TI  - Decommissioning a phosphoric acid production plant: a radiological protection
      case study.
AB  - During a preliminary survey at the area of an abandoned fertilizer plant,
      increased levels of radioactivity were measured at places, buildings,
      constructions and materials. The extent of the contamination was determined and
      the affected areas were characterized as controlled areas. After the quantitative
      and qualitative determination of the contaminated materials, the decontamination
      was planned and performed step by step: the contaminated materials were
      categorized according to their physical characteristics (scrap metals, plastic
      pipes, scales and residues, building materials, etc) and according to their level
      of radioactivity. Depending on the material type, different decontamination and
      disposal options were proposed; the most appropriate technique was chosen taking
      into account apart from technical issues, the legal framework, radiation
      protection issues, the opinion of the local authorities involved as well as the
      owner's wish. After taking away the biggest amount of the contaminated materials,
      an iterative process consisting of surveys and decontamination actions was
      performed in order to remove the residual traces of contamination from the area.
      During the final survey, no residual surface contamination was detected; some
      sparsely distributed low level contaminated materials deeply immersed into the
      soil were found and removed.

PMID- 20813441
TI  - Anatomical study of the unusual origin of a nerve to the mylohyoid muscle and its
      clinical relevance.
AB  - Anomalous patterns in the human body are usually seen in cadaver dissections and
      during investigations. We have studied 50 cadavers of southern Indian men and
      women to find the variable origins of the mylohyoid nerve in the infratemporal
      region. We discovered an unusual origin of the nerve during a routine educational
      dissection. Here we describe the course of the aberrant nerve and its
      distributing branches. Awareness of such anatomical variations could help during
      surgical or dental interventions.

PMID- 20813442
TI  - Stride-to-stride variability is altered during backward walking in anterior
      cruciate ligament deficient patients.
AB  - BACKGROUND: Recently backward walking is used by physical therapists to
      strengthen the hamstring muscles and thus improve the function of the knee joint
      of anterior cruciate ligament deficient patients. The aim of this study was to
      examine the stride-to-stride variability of anterior cruciate ligament deficient
      patients during backward walking. The variation of how a motor behavior emerges
      in time is best captured by tools derived from nonlinear dynamics, for which the
      temporal sequence in a series of values is the facet of interest. METHODS:
      Fifteen patients with unilateral anterior cruciate ligament deficiency and eleven
      healthy controls walked backwards at their self-selected speed on a treadmill
      while three-dimensional knee kinematics were collected (100 Hz). A nonlinear
      measure, the largest Lyapunov Exponent was calculated from the resulted knee
      joint flexion-extension data of both groups to assess the stride-to-stride
      variability. FINDINGS: Both knees of the deficient patients exhibited
      significantly lower Lyapunov Exponent values as compared to the healthy control
      group revealing more rigid movement pattern. The intact knee of the deficient
      patients showed significantly lower Lyapunov Exponent values as compared to the
      deficient knee. INTERPRETATION: Anterior cruciate ligament (ACL) deficiency leads
      to loss of optimal variability regardless of the walking direction (forwards in
      previous studies or backwards here) as compared to healthy individuals. This
      could imply diminished functional responsiveness to the environmental demands for
      both knees of ACL deficient patients which could result in the knees being more
      susceptible to injury.

PMID- 20813443
TI  - Inter-laboratory comparison study on measuring semi-volatile organic chemicals in
      standards and air samples.
AB  - Measurements of semi-volatile organic chemicals (SVOCs) were compared among 21
      laboratories from 7 countries through the analysis of standards, a blind sample,
      an air extract, and an atmospheric dust sample. Measurement accuracy strongly
      depended on analytes, laboratories, and types of standards and samples. Intra
      laboratory precision was generally good with relative standard deviations (RSDs)
      of triplicate injections <10% and with median differences of duplicate samples
      between 2.1 and 22%. Inter-laboratory variability, measured by RSDs of all
      measurements, was in the range of 2.8-58% in analyzing standards, and 6.9-190% in
      analyzing blind sample and air extract. Inter-laboratory precision was poorer
      when samples were subject to cleanup processes, or when SVOCs were quantified at
      low concentrations. In general, inter-laboratory differences up to a factor of 2
      can be expected to analyze atmospheric SVOCs. When comparing air measurements
      from different laboratories, caution should be exercised if the data variability
      is less than the inter-laboratory differences.

PMID- 20813444
TI  - Disorder specific and trans-diagnostic case conceptualisation.
AB  - Case conceptualisation is the process of integrating the unique experience of the
      individual with psychological theory and is often described as a central process
      in effective therapy. Hence, a key question facing a clinician working from a
      cognitive behavioural perspective is which theory should be chosen as the basis
      of the conceptualisation with a particular client? We address this question by
      first considering the strengths and limitations of the disorder specific and
      trans-diagnostic approaches. From this, the differences between the approaches
      are framed as a conundrum or puzzle that is solved through a principle based
      approach to case conceptualisation that allows clinicians to individualise
      therapy by selecting and incorporating the most appropriate theory and research.
      Furthermore, by considering how to achieve lasting improvement for the client we
      emphasise incorporating client strengths and resilience into both disorder
      specific and trans-diagnostic approaches. To achieve this we necessarily extend
      beyond consideration of models of disorders, and draw on models of wellbeing, and
      resilience, and by doing so require theoretical accounts not only of disorders
      but also of resilience.

PMID- 20813445
TI  - Parents who use drugs: accounting for damage and its limitation.
AB  - Parents who use drugs parent in a context of heightened concern regarding the
      damaging effects of parental drug use on child welfare and family life. Yet there
      is little research exploring how parents who use drugs account for such damage
      and its limitation. We draw here upon analyses of audio-recorded depth
      qualitative interviews, conducted in south-east England between 2008 and 2009,
      with 29 parents who use drugs. Our approach to thematic analysis treated accounts
      as co-produced and socially situated. An over-arching theme of accounts was
      'damage limitation'. Most damage limitation work centred on efforts to create a
      sense of normalcy of family life, involving keeping drug use secret from
      children, and investing heavily in strategies to maintain ambiguity regarding
      children's awareness. Our analysis highlights that damage limitation strategies
      double-up in accounts as resources of child protection as well as self
      protection. This illuminates tensions in the multiple functions that accounts of
      damage limitation can serve. We draw a distinction between accounts in which
      damage is qualified and those in which damage is accepted. Accounts of damage
      qualification highlight a theme of 'good enough' parenting. Accounts of damage
      acceptance highlight a theme of 'recovery'. We find that the interview accounts
      operate in response to a regulative norm of 'good parenting' in which one strives
      to deflect damaged identity through narratives of damage qualification and to
      seek understanding and acceptance through narratives of recovery. Noting the
      absence of space for parents who use drugs to openly reflect or talk about the
      challenges they face, we identify the need for social change interventions to
      create enabling environments for earlier help seeking and talking.

PMID- 20813446
TI  - Disability and self-rated health among older women and men in rural Guatemala:
      the role of obesity and chronic conditions.
AB  - Unprecedented population aging in poorer settings is coinciding with the rapid
      spread of obesity and other chronic conditions. These conditions predict
      disability and poor self-rated health and often are more prevalent in women than
      men. Thus, gender gaps in obesity and other chronic conditions may account for
      older women's greater disability and worse self-rated health in poor, rural
      populations, where aging, obesity, and chronic conditions are rapidly emerging.
      In a survey of 604 adults 50 years and older in rural Guatemala, we assessed
      whether gender gaps in obesity and other chronic conditions accounted for gender
      gaps in disability and self-rated health. Obesity strongly predicted gross
      mobility (GM) disability, and the number of chronic conditions strongly predicted
      all outcomes, especially in women. Controlling for gender gaps in body-mass index
      (BMI) and especially the number of chronic conditions eliminated gender gaps in
      GM disability, and controlling for gender gaps in the number of chronic
      conditions eliminated gender gaps in self-rated health. We recommend conducting
      longitudinal cohort studies to explore interventions that may mitigate adult
      obesity and chronic conditions among poor, rural older adults. Such interventions
      also may reduce gender gaps in later-life disability and self-rated health.

PMID- 20813447
TI  - Cell-free synthesis and folding of transmembrane OmpA reveals higher order
      structures and premature truncations.
AB  - We use a cell-free transcription-translation system to monitor the effect of
      different lipids on the synthesis and folding of the transmembrane domain of the
      outer membrane protein OmpA from E. coli under physiological conditions. Folding
      is consistent with previous observations made in vitro at high pH. Synthesis and
      folding yields are optimal in phosphocholine lipids, particularly in short chain
      lipids and small vesicles, while lipid rafts do not promote folding compared to
      the folding in the absence of lipids. Truncated species are observed during
      translation in the presence of the periplasmic chaperone Skp, which likely binds
      to the newly synthesized polypeptide chain during cell-free translation and thus
      prematurely terminate polypeptide chain synthesis. In contrast, folded and
      unfolded dimers of OmpA correlate negatively with folding yields. This suggests
      that dimer formation competes with folding and insertion of monomeric OmpA,
      though folded dimers slowly appear to convert to folded monomers.

PMID- 20813448
TI  - Urogenital development: a four-part story of mesenchymal-epithelial interactions.

PMID- 20813449
TI  - EGF and bFGF pre-treatment enhances neural specification and the response to
      neuronal commitment of MIAMI cells.
AB  - AIMS: Multipotent mesenchymal stromal cells raise great interest for regenerative
      medicine studies. Some MSC subpopulations have the potential to undergo neural
      differentiation, including marrow isolated adult multilineage inducible (MIAMI)
      cells, which differentiate into neuron-like cells in a multi-step neurotrophin 3
      dependent manner. Epidermal and basic fibroblast growth factors are often used in
      neuronal differentiation protocols for MSCs, but with a limited understanding of
      their role. In this study, we thoroughly assessed for the first time the capacity
      of these factors to enhance the neuronal differentiation of MSCs. MATERIALS AND
      METHODS: We have characterized MIAMI cell neuronal differentiation program in
      terms of stem cell molecule expression, cell cycle modifications, acquisition of
      a neuronal morphology and expression of neural and neuronal molecules in the
      absence and presence of an EGF-bFGF pre-treatment. RESULTS: EGF-bFGF pre
      treatment down-regulated the expression of stemness markers Oct4A, Notch1 and
      Hes5, whereas neural/neuronal molecules Nestin, Pax6, Ngn2 and the neurotrophin
      receptor tyrosine kinase 1 and 3 were up-regulated. During differentiation, a
      sustained Erk phosphorylation in response to NT3 was observed, cells began to
      exit from the cell cycle and exhibit increased neurite-like extensions. In
      addition, neuronal beta3-tubulin and neurofilament expression was increased; an
      effect mediated via the Erk pathway. A slight pre-oligodendrocyte engagement was
      noted, and no default neurotransmitter phenotype was observed. Overall,
      mesodermal markers were unaffected or decreased, while neurogenic/adipogenic
      PPARgamma2 was increased. CONCLUSION: EGF and bFGF pre-treatment enhances neural
      specification and the response to neuronal commitment of MIAMI cells, further
      increasing their potential use in adult cell therapy of the nervous system.

PMID- 20813450
TI  - Removal of dicofol from water by immobilized cellulase and its reaction kinetics.
AB  - Researches on the removal of dicofol catalyzed by immobilized cellulase were
      conducted. Factors, such as acidity, temperature, enzyme activity, and initial
      concentration of dicofol, which could influence the removal were studied. The
      optimal pH for dicofol removal by immobilized cellulase was approximately 4-7,
      broader than that for free enzymes. The removal efficiencies for immobilized and
      free cellulase both decreased with increasing initial concentration of dicofol.
      The K(m) for immobilized cellulase was slightly lower than that of free
      cellulase, suggesting that substrate affinity may be enhanced by immobilization.
      The optimum temperatures for immobilized and free cellulase were 45  degrees C
      and 50  degrees C. The removal reaction for immobilized cellulase was found to be
      a first-order reaction. The activation energy was 64.3 kJ mol(-1). The continuous
      oxidation of dicofol carried out in the static system of immobilized cellulase
      showed that the removal efficiency of immobilized cellulase remained after six
      cycles of operation. Thus, the catalytic efficiency of cellulase was improved
      greatly. As evidenced by infrared and gas chromatography-mass spectrometry data,
      the mechanism of reaction might involve an attack by the OH free radical of
      cellulase at a weak location of the dicofol molecule, resulting in the removal of
      three chlorine atoms from dicofol, thus oxygenizing dicofol and producing 4,4'
      dichloro-dibenzophenone.

PMID- 20813451
TI  - Kindlin-2 controls sensitivity of prostate cancer cells to cisplatin-induced cell
      death.
AB  - Resistance to anticancer drugs is often observed in prostate cancer therapy.
      Kindlin-2 was recently found overexpressed during cancer progression. In this
      study, we examined the functional role of Kindlin-2 in cisplatin-induced prostate
      cancer cell death. Kindlin-2 was highly expressed in the androgen-insensitive (PC
      3 and DU-145), but not in the androgen-sensitive cell lines (e.g., LNCaP).
      Overexpression of Kindlin-2 in LNCaP protected the cells from cisplatin-induced
      death, while Kindlin-2 knock-down in PC-3 cells enhanced cisplatin sensitivity.
      Mechanistically, Kindlin-2 regulation of the anti-apoptotic Bcl-xL may explain
      the increased cell death in the absence of Kindlin-2. Taken together, Kindlin-2
      appears to play a functional role in prostate cancer cell sensitivity to
      cisplatin. Targeting Kindlin-2 may therefore improve drug efficacy and reduce
      drug doses, and would likely be beneficial for the treatment of prostate cancer.

PMID- 20813452
TI  - Viral hit and run-oncogenesis: genetic and epigenetic scenarios.
AB  - It is well documented that viral genomes either inserted into the cellular DNA or
      co-replicating with it in episomal form can be lost from neoplastic cells.
      Therefore, "hit and run"-mechanisms have been a topic of longstanding interest in
      tumor virology. The basic idea is that the transient acquisition of a complete or
      incomplete viral genome may be sufficient to induce malignant conversion of host
      cells in vivo, resulting in neoplastic development. After eliciting a heritable
      change in the gene expression pattern of the host cell (initiation), the genomes
      of tumor viruses may be completely lost, i.e. in a hit and run-scenario they are
      not necessary for the maintenance of the malignant state. The expression of viral
      oncoproteins and RNAs may interfere not only with regulators of cell
      proliferation, but also with DNA repair mechanisms. DNA recombinogenic activities
      induced by tumor viruses or activated by other mechanisms may contribute to the
      secondary loss of viral genomes from neoplastic cells. Viral oncoproteins can
      also cause epigenetic dysregulation, thereby reprogramming cellular gene
      expression in a heritable manner. Thus, we expect that epigenetic scenarios of
      viral hit and run-tumorigenesis may facilitate new, innovative experiments and
      clinical studies in spite of the fact that the regular presence of a suspected
      human tumor virus in an early phase of neoplastic development and its subsequent
      regular loss have not been demonstrated yet. We propose that virus-specific
      "epigenetic signatures", i.e. alterations of the host cell epigenome, especially
      altered DNA methylation patterns, may help to identify viral hit and run
      oncogenic events, even after the complete loss of tumor viruses from neoplastic
      cells.

PMID- 20813453
TI  - Immobilized redox mediator on metal-oxides nanoparticles and its catalytic effect
      in a reductive decolorization process.
AB  - Different metal-oxides nanoparticles (MONP) including alpha-Al(2)O(3), ZnO and
      Al(OH)(3), were utilized as adsorbents to immobilize anthraquinone-2,6
      disulfonate (AQDS). Immobilized AQDS was subsequently tested as a solid-phase
      redox mediator (RMs) for the reductive decolorization of the azo dye, reactive
      red 2 (RR2), by anaerobic sludge. The highest adsorption capacity of AQDS was
      achieved on Al(OH)(3) nanoparticles, which was ~0.16 mmol g(-1) at pH 4.
      Immobilized AQDS increased up to 7.5-fold the rate of decolorization of RR2 by
      anaerobic sludge as compared with sludge incubations lacking AQDS. Sterile
      controls including immobilized AQDS did not show significant (<3.5%) RR2
      decolorization, suggesting that physical-chemical processes (e.g. adsorption or
      chemical reduction) were not responsible for the enhanced decolorization
      achieved. Immobilization of AQDS on MONP was very stable under the applied
      experimental conditions and spectrophotometric screening did not detect any
      detachment of AQDS during the reductive decolorization of RR2, confirming that
      immobilized AQDS served as an effective RMs. The present study constitutes the
      first demonstration that immobilized quinones on MONP can serve as effective RMs
      in the reductive decolorization of an azo dye. The immobilizing technique
      developed could be applied in anaerobic wastewater treatment systems to
      accelerate the redox biotransformation of recalcitrant pollutants.

PMID- 20813454
TI  - Removal of chromium from aqueous solution using polyaniline--poly ethylene glycol
      composite.
AB  - The adsorption of chromium compounds from solutions by a composite of
      polyaniline/poly ethylene glycol (PANi/PEG) was investigated in this study.
      Experiments were conducted in batch mode under various operational conditions
      including agitation time, solution pH, PANi/PEG dose and initial concentration of
      chromium salts. Results showed that concentration of PEG at synthesizing stage
      has a significant effect on the capacity of produced composite for removal of
      chromium. Morphologically, PANi/PEG composite is closely dependent on the
      concentration of PEG. Maximum removal of hexavalent chromium was experienced when
      2g/L of PEG was used in synthesis of PANi/PEG. Removal of hexavalent chromium by
      PANi/PEG composite included surface adsorption and reduction reaction. The
      optimum pH was 5 and the equilibrium time for hexavalent chromium removal was
      about 30 min. Investigation of the isothermal characteristics showed that
      chromium adsorption by PANi/PEG composite was in high accordance with Langmuir's
      isotherm.

PMID- 20813455
TI  - Biodegradation of partially hydrolyzed polyacrylamide by bacteria isolated from
      production water after polymer flooding in an oil field.
AB  - Partially hydrolyzed polyacrylamide (HPAM) in production water after polymer
      flooding in oil filed causes environmental problems, such as increases the
      difficulty in oil-water separation, degrades naturally to produce toxic
      acrylamide and endanger local ecosystem. Biodegradation of HPAM may be an
      efficient way to solve these problems. The biodegradability of HPAM in an aerobic
      environment was studied. Two HPAM-degrading bacterial strains, named PM-2 and PM
      3, were isolated from the produced water of polymer flooding. They were
      subsequently identified as Bacillus cereus and Bacillus sp., respectively. The
      utilization of HPAM by the two strains was explored. The amide group of HPAM
      could serve as a nitrogen source for the two microorganisms, the carbon backbone
      of these polymers could be partly utilized by microorganisms. The HPAM samples
      before and after bacterial biodegradation were analyzed by the infrared spectrum,
      high performance liquid chromatography and scanning electronic microscope. The
      results indicated that the amide group of HPAM in the biodegradation products had
      been converted to a carboxyl group, and no acrylamide monomer was found. The HPAM
      carbon backbone was metabolized by the bacteria during the course of its growth.
      Further more, the hypothesis about the biodegradation of HPAM in aerobic
      bacterial culture is proposed.

PMID- 20813456
TI  - Enhanced carbon adsorption treatment for removing cyanide from coking plant
      effluent.
AB  - Batch experiments were conducted to determine the effects of metal loading and
      fixing methods on the capacity of granular activated carbon (GAC) for removing
      cyanide from KCN (pH 11), K(3)Fe(CN)(6) solutions and several SCP effluent
      samples. KI fixed carbon (Cu/KI-GAC) was the most effective among the GAC samples
      tested. Adsorption was the primary mechanism of cyanide removal; catalytic
      oxidation of the adsorbed cyanide on carbon surface contributed a minor amount of
      the observed removal. Four small adsorbers containing the base GAC and 0-100% of
      Cu/KI-GAC were employed for treating a Fenton oxidized/precipitated SCP effluent
      sample. After the start-up period (<3-week) to establish the effective biological
      activated carbon (BAC) function in the adsorbers, the effluents became stable and
      met the discharge limits (COD(Cr)<50mg/L and TCN<0.5mg/L); with >30% Cu/KI-GAC in
      the adsorber, the effluent would meet the discharge limits during the start-up
      phase.

PMID- 20813457
TI  - Remediation of a hexachlorobenzene-contaminated soil by surfactant-enhanced
      electrokinetics coupled with microscale Pd/Fe PRB.
AB  - Treatment of soils contaminated with chlorinated hydrophobic organic compounds
      (CHOCs) remains a challenge for environmental scientists worldwide. In this study
      surfactant-enhanced electrokinetics (SEEK) was coupled with permeable reactive
      barrier (PRB) composed of microscale Pd/Fe to treat a hexachlorobenzene (HCB)
      contaminated soil. A nonionic surfactant, Triton X-100 (TX-100), was selected as
      the solubility-enhancing agent. Five bench-scale tests were conducted to
      investigate the performance of EK-PRB on HCB removal from soils. Results showed
      that the HCB removal was generally increased by a factor of 4 by EK coupled with
      PRB compared with EK alone (60% versus 13%). In the EK-PRB system, HCB was
      removed from soil through several sequential processes: the movement driven by
      electroosmotic flow (EOF) in the anode column, the complete
      adsorption/degradation by the reactive Pd/Fe particles in PRB, and the consequent
      movement by EOF and probable electrochemical reactions in the cathode column. TX
      100 was supposed to be a superior enhancement agent for HCB removal, not only in
      the EOF movement process but also in the Pd/Fe degradation process. This study
      indicates that the combination of SEEK and Pd/Fe PRB is efficient and promising
      to remove CHOCs from contaminated soils.

PMID- 20813458
TI  - Effect of soil organic carbon on the quantification of jet-fuels in soil using
      partitioning tracer method.
AB  - Partitioning tracer method has been studied as an effective technique for
      estimating the light nonaqueous-phase liquid (LNAPL) contamination in the
      subsurface. This study is for investigating the effect of soil organic contents
      on the LNAPL quantification using partitioning tracer method. The sorption
      characteristics of alcohol tracers to the soils having different organic carbon
      contents were evaluated by sorption isotherm experiments. In the column tests,
      the soils were contaminated with jet-fuel and the average saturations of residual
      jet-fuel were estimated by partitioning tracer method and compared with that by
      the volume measurement. The sorption results indicated that considerable amount
      of 4-methyl-2-pentanol and hexanol could be sorbed to the soils and the sorption
      amount of 2-ethyl-1-butanol was relatively smaller than those of the other
      alcohol tracers. The column experiments demonstrated that the accuracy of
      quantification for the jet-fuel by partitioning tracer method should decrease
      with increasing the soil organic carbon contents. However, the accuracy could be
      enhanced by considering the sorption of tracer to the soils, especially for the
      tracer of 2-ethyl-1-butanol.

PMID- 20813459
TI  - Direct blockade of inflammatory hypernociception by peripheral A1 adenosine
      receptors: involvement of the NO/cGMP/PKG/KATP signaling pathway.
AB  - Through activation of the A1 adenosine receptors (A1Rs) at both the central and
      peripheral level, adenosine produces antinociception in a wide range of tests.
      However, the mechanisms involved in the peripheral effect are still not fully
      understood. Therefore, the mechanisms by which peripheral activation of A1Rs
      reduces inflammatory hypernociception (a decrease in the nociceptive threshold)
      were addressed in the present study. Immunofluorescence of rat dorsal root
      ganglion revealed significant expression of A1Rs in primary sensory neurons
      associated with nociceptive pathways. Functionally, peripheral activation of A1Rs
      reduced inflammatory hypernociception because intraplantar (i.pl.) administration
      of an A1R antagonist (DPCPX) enhanced carrageenan-induced hypernociception. On
      the other hand, local (paw) administration of CPA (a selective A1R agonist)
      reversed mechanical hypernociception induced by carrageenan or by the directly
      acting hypernociceptive mediator prostaglandin E(2) (PGE(2)). Down-regulation of
      A1Rs expression in primary nociceptive neurons by intrathecal treatment with
      antisense oligodeoxinucleotides significantly reduced peripheral antinociceptive
      action of CPA. Direct blockade of PGE(2) inflammatory hypernociception by the
      activation of A1Rs depends on the nitric oxide/cGMP/Protein Kinase G/KATP
      signaling pathway because the peripheral antinociceptive effect of CPA was
      prevented by pretreatment with inhibitors of neuronal nitric oxide synthase (N
      propyl-l-arginine), guanylyl cyclase (ODQ), and Protein Kinase G (KT5823) as well
      as with a KATP blocker (glibenclamide). However, this effect of CPA was not
      reduced by naloxone, excluding the participation of endogenous opioids. These
      results suggest that the peripheral activation of A1R plays a role in the
      regulation of inflammatory hypernociception by a mechanism that involves the
      NO/cGMP/PKG/KATP intracellular signaling pathway.

PMID- 20813460
TI  - Response to Drs. Bell and Moore commentary regarding the use of intravenous
      ketamine for CRPS.

PMID- 20813461
TI  - The persistence of pain behaviors in patients with chronic back pain is
      independent of pain and psychological factors.
AB  - The primary purpose of the present study was to examine the temporal stability of
      communicative and protective pain behaviors in patients with chronic back pain.
      The study also examined whether the stability of pain behaviors could be
      accounted for by patients' levels of pain severity, catastrophizing, or fear of
      movement. Patients (n=70) were filmed on two separate occasions (i.e., baseline,
      follow-up) while performing a standardized lifting task designed to elicit pain
      behaviors. Consistent with previous studies, the results provided evidence for
      the stability of pain behaviors in patients with chronic pain. The analyses
      indicated that communicative and protective pain behavior scores did not change
      significantly from baseline to follow-up. In addition, significant test-retest
      correlations were found between baseline and follow-up pain behavior scores. The
      results of hierarchical multiple regression analyses further showed that pain
      behaviors remained stable over time even when accounting for patients' levels of
      pain severity. Regression analyses also showed that pain behaviors remained
      stable when accounting for patients' levels of catastrophizing and fear of
      movement. Discussion addresses the potential contribution of central neural
      mechanisms and social environmental reinforcement contingencies to the stability
      of pain behaviors. The discussion also addresses how treatment interventions
      specifically aimed at targeting pain behaviors might help to augment the overall
      impact of pain and disability management programs.

PMID- 20813462
TI  - Assisting couples to develop healthy relationships: effects of couples
      relationship education on cortisol.
AB  - INTRODUCTION: Couple conflict in unhappy marriages is suggested to impair
      individual health via chronic psychophysiological stress reactions in couples'
      everyday lives. As a consequence, we hypothesized that standard couples
      relationship education (CRE) would decrease psychophysiological stress, namely
      salivary cortisol levels, during couple conflict in the laboratory as compared to
      a standard psychological stress paradigm. We considered cortisol to be of
      particular interest in this context, as it mediates endocrine and immune
      responses to stress, and thus might influence couples' health. METHODS: Salivary
      cortisol was repeatedly investigated in 61 couples during (a) a standard
      psychological stress test with no relevance for the couples, and (b) a standard
      couple conflict discussion in the laboratory before and after CRE. In addition,
      increases in self-evaluated relationship quality were analyzed with regard to
      their influence on salivary cortisol. Data were analyzed using multilevel
      modeling. RESULTS: Cortisol responses to the couple-external psychological stress
      test were unaffected by CRE, but specifically cortisol responses during the
      couple conflict discussion were significantly reduced following CRE compared to
      pre-intervention levels. Moreover, cortisol decreases during conflict were
      partially mediated by increases in self-reported relationship quality following
      CRE. CONCLUSIONS: These data suggest that CRE might buffer the harmful effects of
      repeated conflict in close relationships. Rather than ameliorating overall stress
      resilience, CRE might thus specifically improve individual health through
      increased relationship quality and reduced HPA axis activity during couple
      conflict.

PMID- 20813463
TI  - Early temperament, propensity for risk-taking and adolescent substance-related
      problems: a prospective multi-method investigation.
AB  - One hundred thirty seven adolescents (M=15.3 yrs, SD=1.0 yr, n=72 girls) were
      recruited into temperament groups when they were 4 months of age based on
      reactivity to novel auditory/visual stimuli (Fox, Henderson, Rubin, Calkins, &
      Schmidt, 2001). Behavioral inhibition was observed across infancy (14 and 24
      months). Additionally, self-reported substance-related problems and behavioral
      risk-taking was assessed during adolescence. High behavioral inhibition increased
      risk for substance-related problems among boys, whereas high behavioral
      inhibition protected against substance-related problems among girls, B=-1.18,
      SE=.48, 95% CI=-2.13 to -.24; p<.05. Additionally, high behavioral inhibition
      protected lower risk-taking children from adolescent substance-related problems
      whereas high behavioral inhibition increased risk for substance-related problems
      among higher risk-taking children, B=.04, SE=.02, 95% CI=.00 to .08. Findings
      from this prospective, multi-informant, longitudinal study suggest that risk
      taking and gender may interact with temperamental traits to place adolescents at
      differential risk for substance-related related behavior problems.

PMID- 20813464
TI  - Natural faecal fluorophores and the potential of chlorophyll based markers to
      optimise fluorescence as a real-time solution for the detection of faecal
      contamination on carcasses.
AB  - More accurate and sensitive visualisation of faecal contamination in the abattoir
      would significantly reduce the risk posed by harbouring pathogenic micro
      organisms. We carried out a preliminary investigation of the range of
      fluorophores found naturally in faeces from typical ruminant diets. Sixteen ewes
      were offered either: i) fresh forage (FF), ii) grass silage (GS), iii) grass hay
      (GH) or iv) concentrate and barley straw (CB). Animals offered FF diets had a
      greater concentration (P<0.001) of chlorophyll based compounds in their faeces
      and subsequent fluorescent emission spectra. In a second experiment we
      investigated a range of fluorescent markers against a basal concentrate and
      barley straw diet. Ten Cheviot sheep were split into five treatment groups during
      a duplicate 5 * 5 Latin square design. Four of the groups received a chlorophyll
      based marker at a rate of 2g/d: i) Mg-Chlorophyllin (MgC), ii) Fe-Chlorophyllin
      (FeC), iii) Zn-Chlorophyllin (ZnC) or iv) Spirulina (Chlorophyll a extract from
      blue green algae, Sp). The last group received no supplement as the control
      (Con). The appearance of chlorophyllin markers and their derivatives in faeces
      was similar with mean concentrations of 3.1 and 7.2 MUg/g DM, respectively. The
      most intense fluorescent signal was shown with MgC followed by ZnC, FeC, Sp and
      Con at 685 nm. The use of markers in pre-slaughter diets would improve the
      accuracy of faecal detection as a result of greater fluorescence and specific
      emission wavelengths which do not overlap with natural meat components to help
      with visualisation.

PMID- 20813465
TI  - ACR Appropriateness Criteria(r) on Induction and Adjuvant Therapy for Stage N2
      Non-Small-Cell Lung Cancer: expert panel on radiation oncology-lung.
AB  - "The American College of Radiology seeks and encourages collaboration with other
      organizations on the development of the ACR Appropriateness Criteria through
      society representation on expert panels. Participation by representatives from
      collaborating societies on the expert panel does not necessarily imply society
      endorsement of the final document."

PMID- 20813466
TI  - Effect of hyperoxygenation on tissue pO2 and its effect on radiotherapeutic
      efficacy of orthotopic F98 gliomas.
AB  - PURPOSE: Lack of methods for repeated assessment of tumor pO(2) limits the
      ability to test and optimize hypoxia-modifying procedures being developed for
      clinical applications. We report repeated measurements of orthotopic F98 tumor
      pO(2) and relate this to the effect of carbogen inhalation on tumor growth when
      combined with hypofractionated radiotherapy. METHODS AND MATERIALS: Electron
      paramagnetic resonance (EPR) oximetry was used for repeated measurements of tumor
      and contralateral brain pO(2) in rats during 30% O(2) and carbogen inhalation for
      5 consecutive days. The T(1)-enhanced volumes and diffusion coefficients of the
      tumors were assessed by magnetic resonance imaging (MRI). The tumors were
      irradiated with 9.3 Gy x 4 fractions in rats breathing 30% O(2) or carbogen to
      determine the effect on tumor growth. RESULTS: The pretreatment F98 tumor pO(2)
      varied between 8 and 16 mmHg, while the contralateral brain had 41 to 45 mmHg
      pO(2) during repeated measurements. Carbogen breathing led to a significant
      increase in tumor and contralateral brain pO(2); however, this effect declined
      over days. Irradiation of the tumors in rats breathing carbogen resulted in a
      significant decrease in tumor growth and an increase in the diffusion coefficient
      measured by MRI. CONCLUSIONS: The results provide quantitative measurements of
      the effect of carbogen inhalation on intracerebral tumor pO(2) and its effect on
      therapeutic outcome. Such direct repeated pO(2) measurements by EPR oximetry can
      provide temporal information that could be used to improve therapeutic outcome by
      scheduling doses at times of improved tumor oxygenation. EPR oximetry is
      currently being tested for clinical applications.

PMID- 20813467
TI  - [Termination of pregnancy and placenta previa, interest of performing feticide
      before the labor induction?].
AB  - OBJECTIVES: Study of maternal morbidity when termination of pregnancy (TOP) is
      associated with placenta previa and study of the interest of performing feticide
      before labor induction. PATIENTS AND METHODS: This is a retrospective case
      control study with two groups of matched women: the case group (women with
      placenta previa) and the control group (women without placenta previa). Maternal
      morbidity have been studied and compared between the two groups and in the case
      group, between women who had feticide between labor induction and women who did
      not have feticide. RESULTS: Between 1996 and 2009, we identified 15 cases of TOP
      with placenta previa (seven complete placentas previa and eight low lying
      placenta including partial and marginal placenta previa) who have been matched
      with 29 women. In the case group, eight women had feticide before labor
      induction, six women had no feticide and one woman had feticide the same day of
      labor induction. Maternal morbidity was increased in this group but without major
      complications (four hemorrhages during labor, two postpartum hemorrhages, four
      transfused patients and mean difference of hemoglobin level was 1.5 g/dl in the
      case group versus no hemorrhage during labor, no postpartum hemorrhage, no
      transfusion and mean difference of hemoglobin level was 0.5 g/dl in the control
      group; P<0.005). Performing feticide before labor induction allowed a non
      significant reduction of mean loss of hemoglobin and of the number of women who
      needed transfusions. CONCLUSION: A vaginal delivery in cases of TOP with placenta
      previa and even totally recovering seems a reasonable solution; performing
      feticide before labor induction could decrease loss of blood but further studies
      are needed.

PMID- 20813468
TI  - EcPV2 DNA in equine squamous cell carcinomas and normal genital and ocular
      mucosa.
AB  - Squamous cell carcinoma (SCC) represents the most common malignant tumour of the
      eye and external genitals in horses. Comparable to humans, papillomaviruses (PV)
      have been proposed as etiological agents of cancer in horses and recently, Equine
      papillomavirus type 2 (EcPV2) has been identified in genital SCCs. Hitherto it
      had never been demonstrated in ocular SCCs. The first goal of this study was to
      determine the prevalence of EcPV2 DNA in tissue samples from equine genital and
      ocular SCCs, genital papillomas and penile intraepithelial neoplasia (PIN)
      lesions, using EcPV2-specific PCR. The second goal was to investigate the
      possibility of latent EcPV2 infection in the genital and ocular mucosa of healthy
      horses on swabs obtained from the eye, penis, vulvovaginal region and cervix.
      EcPV2 DNA was detected in all genital SCCs (17/17), genital papillomas (8/8), PIN
      lesions (11/11) and ocular SCCs (9/9). In healthy horses, EcPV2 DNA was detected
      in 43% (17/40) of penile swabs, 53% (9/17) of vulvovaginal swabs, 47% (8/17) of
      cervical swabs and 57% (32/56) of ocular swabs. This study confirms the presence
      of EcPV2 DNA in equine genital SCCs. Moreover, we demonstrate for the first time
      its involvement in other genital lesions and in ocular SCCs and latent EcPV2
      infections in normal genital (including cervical) and ocular equine mucosa. The
      close relatives of EcPV2 are associated to cutaneous lesions, and this virus is
      not related to high-risk human papillomaviruses causing cervical cancer. Thus,
      similar viral tropism does not imply close evolutionary relationship.

PMID- 20813469
TI  - Lipid peroxidation and generation of hydrogen peroxide in frozen-thawed ram semen
      cryopreserved in extenders with antioxidants.
AB  - The objective of this study was to evaluate the effect of addition of the
      antioxidants Trolox and catalase to a ram semen cryopreservation extender on
      lipid peroxidation and hydrogen peroxide generation on the extender and in the
      thawed semen. Semen was collected from 23 Santa Ines rams (one ejaculate per ram)
      and diluted at 32 degrees C to a concentration of 400*106 cells/ml in one of the
      following solution: Tris-egg yolk extender (control), or the same extender
      supplemented with either 50MUM Trolox/108 sperm (Trolox), 50MUgcatalase/ml
      (Catalase) or a combination of Trolox and catalase (Tro+cat, 50MUM Trolox/108
      sperm and 50MUg catalase/ml). The semen was loaded into 0.25ml straws, cooled and
      frozen in a programmable freezer and subsequently stored in liquid nitrogen.
      Prior to evaluation, frozen straws were thawed in a water bath (42 degrees C for
      20s). Lipid peroxidation (LPO), both spontaneous and catalyzed, on the semen and
      the extender were measured using the thiobarbituric acid (TBA) assay in
      accordance with the method described by Buege and Aust (1978). Hydrogen peroxide
      (H2O2) generation was measured using the horseradish peroxidase-dependent
      oxidation of phenol red to a derivative with absorbance at 610nm, according to
      the method described by Pick and Keisari (1980). Spontaneous LPO resulted in the
      least production of thiobarbituric acid-reactive substances (TBARS) in the
      Tro+cat (1.37+/-0.02nMol/108 sperm), compared to amounts in the other treatments
      groups. In the catalyzed LPO experiments, the least (P<0.05) amounts of TBARS
      were observed in Trolox (2.52+/-0.02nMol/108 sperm) and Tro+cat (2.54+/
      0.02nMol/108 sperm) groups, compared to the control (3.81+/-0.02nMol/108 sperm)
      and catalase (3.83+/-0.02nMol/108 sperm) groups. Hydrogen peroxide generation was
      less (P<0.05) in the Trolox (6.00+/-0.18nMol/40*10(6)sperm/+/-40min) and Tro+cat
      (6.08+/-0.18nMol/40*106sperm/+/-40min) groups than in the control (6.97+/
      0.18nMol/40*106 sperm/+/-40min) and catalase (6.53+/-0.18nMol/40*106 sperm/+/
      40min) groups. Compared to the control group, Trolox and catalase treatment
      significantly reduced TBARS in catalyzed LPO and hydrogen peroxide concentrations
      in the samples (P<0.05). ROS (reactive oxygen species) generation occurred in all
      extenders, without sperm cells. The data presented provide evidence that ROS are
      produced in ram semen, both in the extender and during the freezing and thawing
      process. In addition, the data suggest that the antioxidants Trolox and catalase
      may be used to control the oxidative stress imposed on ram spermatozoa by the
      cryopreservation process.

PMID- 20813470
TI  - Menopause and aging: changes in the immune system--a review.
AB  - BACKGROUND: The higher risk of women developing autoimmune diseases suggests that
      immune system is mediated by sex steroids. OBJECTIVE: To review the effects of
      aging and menopause in immune system. METHODS: A systematic review of in vitro,
      animal and human studies involving aging and menopause and immune system was
      carried out. An electronic search based on Internet search engines, MEDLINE (1966
      June 2010) and the Cochrane Controlled Clinical Trials Register was done.
      RESULTS: After crossing-cleaning the reference lists, a total of 688 studies
      dealing with immune system and menopause were identified. Of them, 30 were
      considered selectable. The concept of immunosenescence reflects changes in both
      cellular and serological immune responses throughout the process of generating
      specific response to foreign antigens. This may be related with a higher
      incidence of infectious and chronic diseases. After menopause, there is an
      increase in pro-inflammatory serum markers (IL1, IL6, TNF-alpha), an increase in
      response of the immune blood cells to these cytokines, a decrease in CD4 T and B
      lymphocytes and a decrease in the cytotoxic activity of NK cells. Additionally,
      IL-6 is a key factor in bone resorption and also seems to be associated with
      other diseases more common after menopause such as diabetes, atherosclerosis and
      cardiovascular disease. CONCLUSIONS: Most of the studies suggested that in
      addition to age, in postmenopausal women, changes of the immune system have been
      attributed to estrogen deprivation. Furthermore, recent studies point out changes
      in immune response related to use or cessation of hormone replacement at
      menopause.

PMID- 20813471
TI  - Estrogen exposure and bladder cancer risk in Egyptian women.
AB  - OBJECTIVE: To examine associations between reproductive history and urinary
      bladder cancer in Egyptian women. METHODS: We used questionnaire data from an
      ongoing, multicenter case-control study in Egypt. Controls were matched on age
      and residence area. This analysis focused on female cases with confirmed
      urothelial (UC) and squamous cell (SCC) carcinoma of the bladder. RESULTS: We
      recruited 779 women (540 controls, 239 cases; >98.0% nonsmokers). Younger age at
      menopause (<45 y) and older age at first pregnancy (>18 y) were factors
      significantly associated with increased risk of bladder cancer, even after
      adjusting for schistosomiasis history and other covariates in the multivariable
      logistic model; adjusted odds ratio and 95% confidence intervals were 1.98 (1.41,
      2.77) and 6.26 (3.46, 11.34), respectively. On the other hand, multiple
      pregnancies or use of oral contraceptives were associated with decreased odds of
      having bladder cancer. Similar associations were observed with UC and SCC when
      analyzed separately; however, the magnitude of association with SCC was lower
      than with UC. CONCLUSION: Our data suggest that early estrogen exposure, or the
      relative lack of it, plays a role in urinary bladder carcinoma development among
      Egyptian women.

PMID- 20813472
TI  - Postmortem injuries inflicted by crawfish: morphological and histological
      aspects.
AB  - A scavenging postmortem crawfish (Austropotamobius pallipes) is presented. A 60
      year-old woman was found dead immersed in 2m of water in an artificial lack near
      a dam. The divers, on discovering the body, observed numerous crawfish near the
      face, the abdomen and the hands of the cadaver that disappeared at their
      approach. Her face showed extensive hemorrhagic lesions of the eyelids, lips and
      neck, initially attributed by the police investigators to a possible criminal
      assault. On autopsy, the face injuries were identified as a postmortem defect by
      animal scavenging. We present the macro- and microscopic aspects of these
      postmortem changes in relation to animal predation.

PMID- 20813473
TI  - Homicide-suicide in the United States, 1968-1975.
AB  - This paper describes for the first time the epidemiology of homicide-suicide
      events in the whole of the United States using archival data. From 1968 to 1975,
      there were 2215 homicide-suicide events out of 123,467 homicides. The mean rate
      of homicide-suicide events was 0.134 per 100,000 per year. The murderers in these
      events differ from the typical murderer and the typical suicide in socio
      demographic characteristics. Details of the characteristics of this population
      may be valuable for understanding the circumstances of homicide-suicide events
      and planning preventive measures.

PMID- 20813475
TI  - Multinodular fatty sparing.

PMID- 20813476
TI  - Characterization of heterotrophic nitrifying bacteria with respiratory
      ammonification and denitrification activity--description of Paenibacillus
      uliginis sp. nov., an inhabitant of fen peat soil and Paenibacillus purispatii
      sp. nov., isolated from a spacecraft assembly clean room.
AB  - In the course of studying the influence of N-fertilization on N(2) and N(2)O flux
      rates in relation to soil bacterial community composition of a long-term
      fertilization experiment in fen peat grassland, a strain group was isolated that
      was related to a strain isolated from a spacecraft assembly clean room during
      diversity studies of microorganisms, which withstood cleaning and bioburden
      reduction strategies. Both the fen soil isolates and the clean room strain
      revealed versatile physiological capacities in N-transformation processes by
      performing heterotrophic nitrification, respiratory ammonification and
      denitrification activity. Phylogenetic analysis based on 16S rRNA gene sequences
      demonstrated that the investigated isolates belonged to the genus Paenibacillus.
      Sequence similarities lower than 97% in comparison to established species
      indicated a separate species position. Except for the peptidoglycan type (A4alpha
      L-Lys-D-Asp), chemotaxonomic features of the isolates matched the genus
      description, but differences in several physiological characteristics separated
      them from related species and supported their novel species status. Despite a
      high 16S rRNA gene sequence similarity between the clean room isolate ES_MS17(T)
      and the representative fen soil isolate N3/975(T), DNA-DNA hybridization studies
      revealed genetic differences at the species level. These differences were
      substantiated by MALDI-TOF MS analysis, ribotyping and several distinct
      physiological characteristics. On the basis of these results, it was concluded
      that the fen soil isolates and the clean room isolate ES_MS17(T) represented two
      novel species for which the names Paenibacillus uliginis sp. nov. (type strain
      N3/975(T)=DSM 21861(T)=LMG 24790(T)) and Paenibacillus purispatii sp. nov. (type
      strain ES_MS17(T)=DSM 22991(T)=CIP 110057(T)) are proposed.

PMID- 20813477
TI  - Preface. The seventh workshop, "Brain function investigation by magnetic
      resonance, electrophysiology and molecular imaging".

PMID- 20813478
TI  - Functional connectivity in the rat brain: a complex network approach.
AB  - Functional connectivity analyses of fMRI data can provide a wealth of information
      on the brain functional organization and have been widely applied to the study of
      the human brain. More recently, these methods have been extended to preclinical
      species, thus providing a powerful translational tool. Here, we review methods
      and findings of functional connectivity studies in the rat. More specifically, we
      focus on correlation analysis of pharmacological MRI (phMRI) responses, an
      approach that has enabled mapping the patterns of connectivity underlying major
      neurotransmitter systems in vivo. We also review the use of novel statistical
      approaches based on a network representation of the functional connectivity and
      their application to the study of the rat brain functional architecture.

PMID- 20813479
TI  - NMR spectroscopy and surface tension measurements applied to the study of self
      association of casopitant mesylate, a novel NK1 antagonist.
AB  - The aggregation behaviour of casopitant mesylate, a new NK1 antagonist drug, was
      investigated by means of NMR spectroscopy and surface tension measurements. The
      critical micelle concentration (CMC) in glycine buffer at pH 3.5 was determined
      by analyzing the (1)H NMR chemical shifts variation and the surface tension in
      function of the concentration in a series of solutions. The temperature
      dependence of the CMC was also evaluated by NMR spectroscopy as well as the
      thermodynamic parameters contributing to the aggregation discussed. Surface
      tension measurements were conducted as well in the formulation conditions, e.g.
      in the presence of sodium chloride.

PMID- 20813480
TI  - Fast and precise quantitative analysis of metabolic mixtures by 2D 1H INADEQUATE
      NMR.
AB  - Quantitative analysis of metabolic mixtures by (1)H 1D NMR offers a limited
      potential for precise quantification of biomarkers, due to strong overlap between
      the peaks. Two-dimensional spectroscopy is a powerful tool to unambiguously and
      simultaneously measure a larger number of metabolite contributions. However, it
      is still rarely used for quantification, first because quantitative analysis by
      2D NMR requires a calibration procedure due to the multi-impulsional nature of 2D
      NMR experiments, and above all because of the prohibitive experiment duration
      that is necessary to obtain such a calibration curve. In this work, we develop
      and evaluate a 2D (1)H INADEQUATE protocol for a fast determination of metabolite
      concentrations in complex mixtures. The 2D pulse sequence is carefully optimized
      and evaluated in terms of precision and linearity. Quantitative (1)H INADEQUATE
      2D spectra of metabolic mixtures are obtained in 7 min with a repeatability
      better than 2% for metabolite concentrations as small as 100 MUM and an excellent
      linearity. The method described in this work allows a fast and precise
      quantification of metabolic mixtures, and it forms a promising tool for
      metabonomic studies.

PMID- 20813481
TI  - Detection, identification and quantification of a new de-fluorinated impurity in
      casopitant mesylate drug substance during late phase development: an analytical
      challenge involving a multidisciplinary approach.
AB  - During late phase development of the selective NK1 receptor antagonist casopitant
      mesylate, a de-fluorinated impurity was discovered and quantified by an
      orthogonal analytical approach, using NMR and LC-MS. A dedicated (19)F NMR method
      was initially developed for first line identification and semi-quantification of
      the impurity. Subsequently, a more accurate quantification was achieved by means
      of a selective normal-phase LC-MS method, which was fully validated. The results
      obtained on the development batches of the drug substance were used by the
      project team to set up a suitable control strategy and ultimately to ensure
      patient safety and the progression of the project.

PMID- 20813482
TI  - Spontaneous rupture of the spleen: a rare but serious case of acute abdominal
      pain in pregnancy.
AB  - BACKGROUND: Spontaneous (non-traumatic) rupture of the spleen rarely occurs in
      the setting of a normal spleen, especially during pregnancy. OBJECTIVES: We
      report a case of spontaneous rupture of a normal spleen at 33.7 weeks gestation
      and review the literature with the aim of exploring the etiology, diagnosis, and
      management of this condition during pregnancy. CASE REPORT: A 30-year-old Chinese
      primigravida presented at 33.7 weeks gestation with acute onset of severe,
      constant left upper abdominal pain. She developed acute hypotension. Physical
      examination revealed diffuse abdominal tenderness with rebounding and guarding.
      An emergent cesarean delivery and abdominal exploration was performed. A non
      viable male infant was delivered, and active bleeding was identified at the
      splenic hilum consistent with splenic rupture. A splenectomy was performed, and a
      consumptive coagulopathy was identified and treated. The patient had an
      uncomplicated postoperative course and was discharged home on postoperative day
      15. CONCLUSION: Splenic rupture in pregnancy is a life-threatening complication.
      Early diagnosis and aggressive surgical intervention will allow for optimal
      maternal and perinatal outcome.

PMID- 20813483
TI  - The value of procalcitonin, a novel inflammatory marker, in the diagnosis of
      myocardial infarction and evaluation of acute coronary syndrome patients.
AB  - BACKGROUND: Procalcitonin is a calcitonin precursor that is used as an
      inflammatory biomarker in the plasma of patients with sepsis. OBJECTIVE: The aim
      of this study was to determine the diagnostic accuracy of emergency department
      (ED) point-of-care blood procalcitonin testing in identifying myocardial
      infarction (MI) in patients with chest pain of presumed ischemic origin. METHODS:
      Patients over 18 years of age who presented to the ED with MI-typical chest pain
      of presumed ischemic origin were included in the study. An initial point-of-care
      blood sample was drawn from each study patient for testing procalcitonin,
      troponin T, myoglobin, and creatine kinase-MB levels. A second sample was taken
      4h after admission for a procalcitonin test. Finally, a 6-h post-admission blood
      sample was taken to measure troponin T, myoglobin, and creatine kinase-MB levels
      in each study patient who had an initial negative cardiac marker test. RESULTS: A
      total of 1008 patients with chest pain were admitted to the ED during the study
      period, and a total of 141 patients met study criteria and were entered into the
      study. ED point-of-care blood procalcitonin testing to identify myocardial
      infarction in patients with chest pain of presumed ischemic origin had a
      sensitivity of 38.3% (95% confidence interval [CI] 28.8-47.3%) and a specificity
      of 77.8% (95% CI 70.0-84.4%), a positive likelihood ratio (LR+) of 1.725 and a
      negative likelihood ratio (LR-) of 0.792. The 4th hour diagnostic values
      (sensitivity, specificity, LR+ and LR-) of procalcitonin semi-quantitative (PCT
      Q) testing were 90% (95% CI 80.9-95.7%), 59.3% (95% CI 52.5-63.5%), 2.2, and
      0.16, respectively. CONCLUSION: ED point-of-care testing for procalcitonin had
      poor diagnostic accuracy for predicting myocardial infarction.

PMID- 20813484
TI  - The outcomes of emergency pharmacist participation during acute myocardial
      infarction.
AB  - BACKGROUND: Current guidelines recommend door-to-balloon times of 90 min or less
      for patients presenting to the emergency department (ED) with ST-segment
      elevation myocardial infarction (STEMI). OBJECTIVES: To determine if a clinical
      pharmacist for the ED (EPh) is associated with decreased door/diagnosis-to
      cardiac catheterization laboratory (CCL) time and decreased door-to-balloon time.
      METHODS: A retrospective observational cohort study of ED patients with STEMI
      requiring urgent cardiac catheterization was conducted. Blinded data collection
      included timing of ED and CCL arrival, diagnostic electrocardiogram (ECG), and
      balloon angioplasty. For cases diagnosed after ED arrival, diagnosis time was
      substituted for door time. Diagnosis was the time ST elevations were evident on
      serial ECG. EPh present and not-present groups were compared. During the study
      period there were two EPhs and presence was determined by their scheduled time in
      the ED. Univariate and multivariate analyses was used to detect differences.
      RESULTS: Multivariate analysis of 120 patients, controlled for CCL staff presence
      and arrival by pre-hospital services, determined that EPh presence is associated
      with a mean 13.1-min (95% confidence interval [CI] 6.5-21.9) and 11.5-min (95% CI
      3.9-21.5) decrease in door/diagnosis-to-CCL and door-to-balloon times,
      respectively. Patients were more likely to achieve a door/diagnosis-to-CCL time<=
      30 min (odds ratio [OR] 3.1, 95% CI 1.3-7.8) and<= 45 min (OR 2.9, 95% CI-1.0,
      8.5) and a door-to-balloon time<= 90 min (OR 1.9, 95% CI 0.7-5.5) more likely
      when the EPh was present. CONCLUSIONS: EPh presence during STEMI presentation to
      the ED is independently associated with a decrease in door/diagnosis-to-CCL and
      door-to-balloon times.

PMID- 20813485
TI  - Comparison of 6% hydroxyethyl starch 130/0.4 and saline solution for
      resuscitation of the microcirculation during the early goal-directed therapy of
      septic patients.
AB  - PURPOSE: The aim of this study was to show that 6% hydroxyethyl starch (HES)
      130/0.4 achieves a better resuscitation of the microcirculation than normal
      saline solution (SS), during early goal-directed therapy (EGDT) in septic
      patients. MATERIALS AND METHODS: Patients with severe sepsis were randomized for
      EGDT with 6% HES 130/0.4 (n = 9) or SS (n = 11). Sublingual microcirculation was
      evaluated by sidestream dark field imaging 24 hours after the beginning of EGDT.
      RESULTS: On admission, there were no differences in Sequential Organ Failure
      Assessment score, mean arterial pressure, lactate, or central venous oxygen
      saturation. After 24 hours, no difference arose in those parameters. Sublingual
      capillary density was similar in both groups (21 +/- 8 versus 20 +/- 3
      vessels/mm(2)); but capillary microvascular flow index, percent of perfused
      capillaries, and perfused capillary density were higher in 6% HES 130/0.4 (2.5 +/
      0.5 versus 1.6 +/- 0.7, 84 +/- 15 versus 53 +/- 26%, and 19 +/- 6 versus 11 +/-
      5 vessels/mm(2), respectively, P < .005). CONCLUSIONS: Fluid resuscitation with
      6% HES 130/0.4 may have advantages over SS to improve sublingual
      microcirculation. A greater number of patients would be necessary to confirm
      these findings.

PMID- 20813488
TI  - Outcomes in critically ill patients with hematologic malignancies who received
      renal replacement therapy for acute kidney injury in an intensive care unit.
AB  - INTRODUCTION: In critically ill patients with hematologic malignancies, acute
      kidney injury (AKI) usually occurs in the context of multiple organ failure due
      to various etiologies and is associated with poor prognosis. The objective of the
      present study was to identify the prognostic factors associated with intensive
      care unit (ICU) mortality in patients with hematologic malignancies and AKI
      requiring renal replacement therapy (RRT). METHODS: We retrospectively evaluated
      94 patients with hematologic malignancies and AKI who received RRT in the ICU of
      Samsung Medical Center, Seoul, Korea, between January 2004 and December 2007.
      RESULTS: The study sample included 65 men and 29 women with a median age of 49
      years (interquartile range [IQR], 36-61 years). The median Simplified Acute
      Physiology Score II and Sequential Organ Failure Assessment (SOFA) scores at ICU
      admission were 64 (IQR, 46-79) and 13 (IQR, 9-16), respectively. The RRT for AKI
      was initiated at a median time of 1 day (IQR, 0-4 day) after ICU admission.
      Seventy-two (77%) patients died in the ICU after a median time of 4 days (IQR, 2
      20 days) after the initiation of RRT. Among the 22 patients who survived, 5 (23%)
      required RRT after ICU discharge. Intensive care unit mortality was associated
      with an etiology of AKI, Simplified Acute Physiology Score II score, and SOFA
      score. Modified SOFA (mSOFA) score (defined as the sum of the 5 nonrenal
      components of the SOFA score) at the initiation of RRT was lower in survivors
      than in nonsurvivors. In a multiple logistic regression analysis, ICU mortality
      was independently associated with mSOFA score (odds ratio, 1.83 per mSOFA score
      increase; 95% confidence interval, 1.38-2.42) at the initiation of RRT. The
      estimated area under the curve for mSOFA score was 0.902 (95% confidence
      interval, 0.831-0.972). CONCLUSION: The severity of organ failure, excluding
      renal failure, at initiation of RRT was independently associated with ICU
      mortality in patients with hematologic malignancies and AKI requiring RRT.

PMID- 20813489
TI  - Procalcitonin levels are lower in intensive care unit patients with H1N1
      influenza A virus pneumonia than in those with community-acquired bacterial
      pneumonia. A pilot study.
AB  - PURPOSE: The purpose of the study was to know the kinetics of procalcitonin
      (PCT), C-reactive protein (CRP), and white blood cell (WBC) in critically ill
      patients with H1N1 influenza A virus pneumonia and to compare levels of these
      inflammatory mediators with patients with acute community-acquired bacterial
      pneumonia. MATERIALS AND METHODS: An observational study in a mixed intensive
      care unit (ICU) at a general university hospital was performed. All consecutive
      patients admitted to the ICU with a diagnosis of severe acute community-acquired
      pneumonia from September 2009 to December 2009 were included. Viral (H1N1
      influenza A) and bacterial microbiological diagnoses were done in every patient.
      At admission, demographics, comorbidities, Simplified Acute Physiology Score,
      Sequential Organ Failure Assessment, Lung Injury Score, and Pao(2)/Fio(2) were
      recorded. At admission and after 24, 48, and 120 hours, WBC, CRP, and PCT levels
      were obtained. Finally, hospital and ICU length of stay and mortality were
      recorded. RESULTS: No differences in CRP or WBC were found between H1N1-positive
      patients and H1N1-negative patients (patients with acute community-acquired
      bacterial pneumonia). Procalcitonin levels at admission were lower in H1N1
      positive patients (PCT = 0.4 [0.1-6.1] ng/mL) than in the H1N1-negative patients
      (24.8 [13.1-34.5] ng/mL). Procalcitonin significantly decreased with time but
      remained lower in the H1N1-positive group at all measurements (P < .05 for all
      comparisons). CONCLUSIONS: Among patients admitted to the ICU with pneumonia, the
      PCT level could help identify H1N1 influenza A virus pneumonia and thus enable
      earlier antiviral therapy.

PMID- 20813490
TI  - Reduced mortality with noninvasive hemodynamic monitoring of shock.
AB  - PURPOSE: This study compared clinical outcomes associated with exposure to
      pulmonary artery catheters (PACs), central venous catheters (CVCs), arterial
      pressure waveform analysis for cardiac output (APCO), or no central monitoring
      (NCM) in patients with shock. MATERIALS AND METHODS: We assessed 6929 consecutive
      patients from 2003 to 2006 within a surgical intensive care unit of a university
      hospital, identifying 237 mechanically ventilated patients with shock. RESULTS:
      Adjusted for severity of illness, use of APCO monitoring, compared with other
      options, was associated with reduced intensive care unit mortality (odds ratio
      [OR], 0.37; 95% confidence interval [CI], 0.18-0.77) and 28-day mortality (OR,
      0.43; 95% CI, 0.22-0.85). Other monitors were not associated with changes of 28
      day mortality (CVC: OR, 0.63; 95% CI, 0.34-1.17; PAC: OR, 0.78; 95% CI, 0.36
      1.69) or were associated with increased risk (NCM: OR, 2.29; 95% CI, 1.14-4.61).
      There were significant differences in the fluid and vasoactive drug prescriptions
      among the groups. CONCLUSIONS: This study supports an association between the use
      of APCO monitoring and reduction in mortality in shock compared with traditional
      methods of monitoring. Although it is impossible to exclude the role of
      unrecognized/unrecorded differences among the groups, these findings may result
      from differences in supportive care, directed by monitor technology.

PMID- 20813491
TI  - Toward optimal display of physiologic status in critical care: I. Recreating
      bedside displays from archived physiologic data.
AB  - BACKGROUND: Physiologic data display is essential to decision making in critical
      care. Current displays echo first-generation hemodynamic monitors dating to the
      1970s and have not kept pace with new insights into physiology or the needs of
      clinicians who must make progressively more complex decisions about their
      patients. The effectiveness of any redesign must be tested before deployment.
      Tools that compare current displays with novel presentations of processed
      physiologic data are required. Regenerating conventional physiologic displays
      from archived physiologic data is an essential first step. OBJECTIVES: The
      purposes of the study were to (1) describe the SSSI (single sensor single
      indicator) paradigm that is currently used for physiologic signal displays, (2)
      identify and discuss possible extensions and enhancements of the SSSI paradigm,
      and (3) develop a general approach and a software prototype to construct such
      "extended SSSI displays" from raw data. RESULTS: We present Multi Wave Animator
      (MWA) framework--a set of open source MATLAB (MathWorks, Inc., Natick, MA, USA)
      scripts aimed to create dynamic visualizations (eg, video files in AVI format) of
      patient vital signs recorded from bedside (intensive care unit or operating room)
      monitors. Multi Wave Animator creates animations in which vital signs are
      displayed to mimic their appearance on current bedside monitors. The source code
      of MWA is freely available online together with a detailed tutorial and sample
      data sets.

PMID- 20813492
TI  - Pilot trial of a patient-specific cutaneous electrostimulation device (MC5-A
      Calmare(r)) for chemotherapy-induced peripheral neuropathy.
AB  - CONTEXT: Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose
      limiting and persistent consequence of numerous classes of antineoplastic agents,
      affecting up to 30%-40% of patients. To date, there is no effective prevention or
      therapy. An evolving hypothesis for reducing CIPN pain involves direct nerve
      stimulation to reduce the pain impulse. OBJECTIVES: To evaluate the impact on
      CIPN associated with the MC5-A Calmare(r) therapy device. METHODS: The MC5-A
      Calmare(r) therapy device is designed to generate a patient-specific cutaneous
      electrostimulation to reduce the abnormal pain intensity. Sixteen patients from
      one center received one-hour interventions daily over 10 working days. RESULTS:
      Of 18 patients, 16 were evaluable. The mean age of the patients was 58.6 years
      four men and 14 women-and the duration of CIPN was three months to eight years.
      The most common drugs were taxanes, platinums, and bortezomib (Velcade, Millenium
      Pharmaceuticals, Cambridge MA). At the end of the study (Day 10), a 20% reduction
      in numeric pain scores was achieved in 15 of 16 patients. The pain score fell 59%
      from 5.81+/-1.11 before treatment to 2.38+/-1.82 at the end of 10 days (P<0.0001
      by paired t-test). A daily treatment benefit was seen with a strong statistically
      significant difference between the pre- and post-daily pain scores (P<0.001).
      Four patients had their CIPN reduced to zero. A repeated-measures analysis using
      the scores from all 10 days confirmed these results. No toxicity was seen. Some
      responses have been durable without maintenance. CONCLUSION: Patient-specific
      cutaneous electrostimulation with the MC5-A Calmare(r) device appears to
      dramatically reduce pain in refractory CIPN patients with no toxicity. Further
      studies are underway to define the benefit, mechanisms of action, and optimal
      schedule.

PMID- 20813493
TI  - Measuring families' perceptions of care across a health care system: preliminary
      experience with the Family Assessment of Treatment at End of Life Short form
      (FATE-S).
AB  - CONTEXT: Because the Family Evaluation of Treatment at End of Life (FATE) survey
      was too long for routine use in the Veterans Administration (VA) health care
      system to measure quality of care, a shorter instrument was developed.
      OBJECTIVES: To evaluate the short version of the FATE survey for use as a
      nationwide quality measure in the VA health care system. METHODS: Fifty-one VA
      medical centers, including acute and long-term care, participated in this
      nationwide telephone survey. Family members of the patients were eligible if the
      patients died in a participating facility. One family member per patient was
      selected from medical records using predefined eligibility criteria and invited
      to participate. The survey consists of 14 items describing key aspects of the
      patient's care in his or her last month of life, one global rating, and two open
      ended questions for additional comments. RESULTS: Interviews were completed with
      2827 family members. Overall, the survey showed excellent psychometric
      characteristics, with good homogeneity (e.g., Cronbach's alpha=0.84) and strong
      evidence of discriminant validity. Two survey items have been targeted for
      quality improvement efforts in multisite collaboratives. CONCLUSION: Surveys of
      surrogates offer an important source of quality data that can be used to improve
      the quality of end-of-life care and promote accountability.

PMID- 20813494
TI  - "At the foot of a very long ladder": discussing the end of life with older people
      and informal caregivers.
AB  - CONTEXT: International policy advocates the development of approaches to raise
      public awareness about end-of-life-care issues, so that when people face a final
      illness, they may better articulate their needs for care. This article reports
      findings from one approach of engaging older members of the general public and
      informal caregivers in discussions about end-of-life care. OBJECTIVES: To
      increase understanding of the concerns many older people have around end-of-life
      issues and provide advice and information to address these. METHODS: Listening
      events were delivered across the United Kingdom using principles of focus group
      conduct to facilitate discussions among older people, informal caregivers, and
      representatives from community groups (n=74) in four workshops. Participants
      discussed their feelings, experiences, and concerns about the end of life, guided
      by the booklet Planning for Choice in End-of-Life Care, which was piloted in an
      earlier study. RESULTS: After framework analysis, three themes arose:
      communicating about end-of-life issues, factors that influence individuals'
      concerns about death and dying, and advance care planning. The heterogeneity of
      stories told not only illustrates how people's responses and needs at the end of
      life vary greatly but also reveals shared reactions, experiences, and some
      confusion. The stories also demonstrate people's willingness to engage with
      concerns associated with the end of life and their conviction that this is an
      important area of community action and development. CONCLUSION: Further community
      based solutions to questions of quality of death need to be found, encouraged by
      programs of public education.

PMID- 20813495
TI  - Potential opioid-sparing effect of regular benzodiazepines in dyspnea: longer
      duration of studies needed.

PMID- 20813496
TI  - Acupressure: an overview of systematic reviews.

PMID- 20813497
TI  - Assessment of cognitive functions in individuals with post-traumatic symptoms
      after work-related accidents.
AB  - The investigation of cognitive functions in individuals who developed post
      traumatic symptoms after occupational accidents has been overlooked in the
      relevant literature. The present study was aimed at assessing attention, memory
      and executive functions in individuals with post-traumatic symptoms after a
      workplace accident. Moreover, possible presence of emotional interference from
      trauma-related cues on attentional performance was evaluated. Results showed that
      injured workers exhibited deficits in perceptual-psychomotor skills, executive
      functions, attention and concentration abilities, and memory as compared with
      healthy controls. With regards to emotional interference on attention, injured
      workers were found to perform significantly worse than controls specifically when
      exposed to trauma-related pictures. Overall, these findings suggest that post
      traumatic symptoms following a workplace accident are associated with several
      cognitive and emotional dysfunctions, that should be carefully evaluated to help
      reduce the frequency and the adverse consequences of occupational accidents.

PMID- 20813498
TI  - Spectral moment analysis of unilateral vocal fold paralysis.
AB  - Many acoustic measures have been used to assess and track the voices of patients
      with voice problems. Some of these measures rely on the accurate measurement of
      fundamental frequency to produce reliable results. Patients with voice disorders
      often produce voices with considerable quasiperiodicity or aperiodicity. There
      are other measurements that do not depend on the accurate tracking of fundamental
      frequency by computing the spectrum of the sound and comparing different parts of
      the spectrum. The moments of the spectral distribution may also be important
      measurements to use in patients with voice problems. Several studies have
      reported good results using these measures to track treatment progress. In this
      study, spectral moments were used to assess the effectiveness of two treatment
      approaches in patients with unilateral vocal fold paralysis (UVFP). Twenty-six
      patients with UVFP and dysphonia (16 female and 10 male patients) were studied.
      Thirteen underwent surgery to improve their voice, whereas the other 13 received
      voice therapy. The patients were recorded at three time intervals: before the
      start of treatment, about 1 month after treatment has been completed, and at 3
      months after treatment. They produced three types of speech material, vowels /ah/
      and /oo/ and a simple sentence. The first four spectral moments (mean, standard
      deviation, skewness, and kurtosis) were computed from the long-term average
      spectrum. Severity of voice dysphonia was rated on a 11-point scale ranging from
      0 (normal) to 10 (aphonic). There were no statistical differences between males
      and females for any of the four moments. There was also no difference between the
      two treatment types. There were differences among the three types of speech
      material for moments 1 and 3. There were also differences for moments 1, 2, and 3
      for the three treatment conditions with most of the differences occurring between
      the pretreatment and first posttreatment condition. Severity of dysphonia
      decreased significantly from the pretreatment to either of the two posttreatment
      conditions. Spectral moments appear to be viable acoustic measurements to use to
      assess the effects of treatment on the voice of patients with UVFP.

PMID- 20813499
TI  - Enculturing brains through patterned practices.
AB  - Recent findings in neuroscience have shown differential patterns in brain
      activity in response to similar stimuli and activities across cultural and social
      differences. This calls for a framework to understand how such differences may
      come to be implemented in brains and neurons. Based on strands of research in
      social anthropology, we argue that human practices are characterized by
      particular patterns, and that participating in these patterns orders how people
      perceive and act in particular group- and context-specific ways. This then leads
      to a particular patterning of neuronal processes that may be detected using e.g.
      brain imaging methods. We illustrate this through (a) a classical example of
      phoneme perception (b) recent work on performance in experimental game play. We
      then discuss these findings in the light of predictive models of brain function.
      We argue that a 'culture as patterned practices' approach obviates a rigid nature
      culture distinction, avoids the problems involved in conceptualizing 'culture' as
      a homogenous grouping variable, and suggests that participating as a competent
      participant in particular practices may affect both the subjective (first person)
      experience and (third person) objective measures of behavior and brain activity.

PMID- 20813500
TI  - A comparison of autogenous bone graft combined with deproteinized bovine bone and
      autogenous bone graft alone for treatment of alveolar cleft.
AB  - This study assessed the use of composite autogenous bone and deproteinized bovine
      bone (DBB) for repairing alveolar cleft compared with autogenous bone alone in
      terms of clinical outcomes and patient morbidity. 30 patients with a mean age of
      10.2+/-1.7 years were randomly divided into two groups. Group I used autogenous
      cancellous bone graft harvested from the anterior iliac crests by the
      conventional trapdoor approach. Group II used a composite of DBB and autogenous
      cancellous bone harvested by a trephine bone collector; the proportion of 1:1 by
      volume was used. The bone graft quantities of both groups decreased with time.
      Their average changes were not statistically different over 24 months after
      grafting. The canines of both groups could spontaneously or orthodontically erupt
      through the grafting areas. Patients in group II recovered from uncomfortable
      walking significantly faster than those in group I (p<0.05) and their duration of
      hospital stay was significantly shorter than those in group I (p<0.05). The
      average operation time, intra-operative blood loss and postoperative pain were
      less in group II than in group I (p>0.05).

PMID- 20813501
TI  - Protein kinase Cdelta is associated with 14-3-3 phosphorylation in seizure
      induced neuronal death.
AB  - Prolonged seizures cause significant damage to the brain, and cellular damage due
      to status epilepticus may be related to the pathogenesis of epilepsy. Protein
      kinase Cdelta (PKCdelta) mediates multiple cell death signalings, and 14-3-3
      proteins regulate survival pathways in brain, sequestering certain pro-apoptotic
      proteins. Presently, we examined the association between PKCdelta and 14-3-3 with
      seizure-induced neuronal death using mouse model. Status epilepticus was induced
      by systemic kainic acid. Kainate-induced seizures caused an increase in levels of
      cleaved PKCdelta in the hippocampus, along with up-regulation of cleaved caspase
      3 and phospho-14-3-3zeta (Ser58), as well as extensive hippocampal cell death as
      visualized with Fluoro-Jade B and anti-active caspase-3 staining. Furthermore, co
      immunoprecipitation or double immunofluorescence analysis revealed that PKCdelta
      interacts with 14-3-3, and interaction between PKCdelta and 14-3-3 was
      significantly enhanced in the hippocampus after seizures, paralleling increased
      interaction between Bad and Bcl-x(L). Moreover, terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive
      cells had upregulated phospho-14-3-3zeta (Ser58) in the hippocampus after
      seizures. These findings suggest that PKCdelta and phospho-14-3-3 are associated
      with apoptotic cell death in the hippocampus after seizures, and targeting
      PKCdelta or phospho-14-3-3 may be potently protective against seizure-induced
      neuronal injury.

PMID- 20813502
TI  - Incidence of schizophrenia among Moroccan immigrants to the Netherlands.

PMID- 20813503
TI  - Job conflicts and suicide among physicians.

PMID- 20813504
TI  - Heart rate measured in the acute aftermath of trauma can predict post-traumatic
      stress disorder: a prospective study in motor vehicle accident survivors.
AB  - OBJECTIVE: To determine whether increased physiological arousal immediately after
      trauma or at emergency admission can predict post-traumatic stress disorder
      (PTSD) in motor vehicle accident (MVA) survivors with physical injuries. METHODS:
      We included 119 MVA survivors with physical injuries. In this prospective cohort
      study, heart rate (HR) and blood pressure (BP) were assessed during ambulance
      transport (T1) and at hospital admission (T2). One and four months after the
      accident, we assessed patients for PTSD (Davidson trauma scale, confirmed with
      the structured clinical interview for DSM-IV axis I disorders). Multivariate
      logistic regression models assessed the relationship between HR or BP and PTSD.
      RESULTS: PTSD was diagnosed in 54 (45.4%) patients at 1 month and in 39 (32.8%)
      at 4 months. In the multivariate analysis, HR at T1 or at T2 predicted PTSD at 1
      month (OR=1.156, 95% CI [1.094;1.221] p<0.0001). Only HR at T1 (not at T2)
      predicted PTSD at 4 months (OR=1.059, 95% CI [1.013; 1.108] p=0.012). Injury
      severity predicted PTSD at 4 months (OR=1.207, 95% CI [1.085; 1.342] p=0.001). A
      cut-off of 84 beats per minute yielded a sensitivity of 62.5% and a specificity
      of 75.0% for PTSD. CONCLUSIONS: HR measured at the scene of MVA and severity of
      injury predicted PTSD 4 months later.

PMID- 20813505
TI  - Point prevalence of major depression in Estonia. Results from the 2006 Estonian
      Health Survey.
AB  - AIM: The study focuses on the point prevalence of major depressive episode in the
      Estonian population in 2006 and assesses the relationship of sociodemographic
      factors, health status indicators, alcohol use, and previous depressive episodes
      to major depression. METHODS: The present major depressive episode was assessed
      within the nationally representative, cross-sectional 2006 Estonian Health Survey
      (EHIS 2006), in which non-institutionalized individuals aged 18-84 years (n=6105)
      were interviewed using the Mini-International Neuropsychiatric Interview (MINI).
      RESULTS: The point prevalence of major depressive episode in the Estonian
      population was 5.6%. Depression was higher among females, in the non-Estonian
      ethnic group, among people older than 40 years, and in the lower-income group.
      CONCLUSIONS: The point prevalence of major depressive episodes was comparable
      with the results of other population surveys, being a little higher than the
      average. Age, income, ethnicity, health status, self-rated health, and previous
      depressive episode were independent associates of depression.

PMID- 20813506
TI  - Longitudinal changes of insight in first episode psychosis and its relation to
      clinical symptoms, treatment adherence and global functioning: one-year follow-up
      from the Eiffel study.
AB  - OBJECTIVES: The Eiffel study is a longitudinal, naturalistic study of patients
      with first episode psychosis (FEP) designed to evaluate the predictive value of
      defective insight on treatment adherence and global functioning. METHODS: Five
      hundred seventy-seven patients with FEP were assessed at baseline and at a 1-year
      follow-up. They were compared in terms of sociodemographic factors,
      psychopathology, insight, treatment adherence and functional outcome.
      Longitudinal functionality was prospectively assessed with the clinical global
      impression (CGI) and global assessment of functioning (GAF) rating scales.
      RESULTS: At baseline, up to 50% of our sample presented with a lack of insight.
      Most clinical symptoms, including insight, improved over the follow-up period.
      Insight, education and social withdrawal significantly predicted CGI and GAF at
      follow-up. Insight and level of education were predictive of treatment adherence.
      CONCLUSIONS: Insight significantly predicted the general clinical course,
      treatment adherence and functional outcome in our FEP sample after 1 year. Only
      education additionally accounted for the longitudinal course. Since our results
      suggest that better insight improves treatment adherence and consequently
      clinical course and functional outcome, insight could be a specific target of
      treatment in early intervention programs.

PMID- 20813507
TI  - Disruptive symptoms in childhood and adolescence and early initiation of tobacco
      and cannabis use: the Gazel Youth study.
AB  - PURPOSE: To examine the link between symptoms of hyperactivity-inattention and
      conduct disorder in childhood, and the initiation of tobacco and cannabis use,
      controlling for other behavioral symptoms, temperament and environmental risk
      factors. METHOD: The sample (N=1107 participants, aged 4 to 18 years at baseline)
      was recruited from the population-based longitudinal Gazel Youth study with a
      follow-up assessment 8 years later. Psychopathology, temperament, environmental
      variables, and initiation of tobacco and cannabis use were self-reported. Event
      time analyses were performed to assess the effects of childhood disruptive
      symptoms on age at first use of tobacco and cannabis. RESULTS: Proportional
      hazard models revealed that participants with high levels of childhood symptoms
      of both hyperactivity-inattention and conduct disorder were at highest risk of
      early tobacco initiation (in males: hazard ratio [HR]=2.05; confidence interval
      [CI]: 1.24-3.38; in females: HR=2.01; CI: 1.31-3.09), and, in males, of early
      cannabis initiation (HR=1.95; CI: 1.04-3.64). Temperament, through activity in
      both males and females and negative emotionality in females, was also associated
      to early substance use initiation. CONCLUSIONS: Children who simultaneously have
      high levels of symptoms of hyperactivity-inattention and conduct disorder are at
      increased risk for early substance initiation. These associations may guide
      childhood health professionals to consider the liability for early substance
      initiation in high-risk groups.

PMID- 20813508
TI  - Panic disorder and subthreshold panic in the UK general population: epidemiology,
      comorbidity and functional limitation.
AB  - OBJECTIVE: The epidemiology of panic disorder has not been investigated in the
      past in the UK using a nationally representative sample of the population. The
      aim of the present paper was to examine the epidemiology, comorbidity and
      functional impairment of subthreshold panic and panic disorder with or without
      agoraphobia. METHOD: We used data from the 2000 Office for National Statistics
      Psychiatric Morbidity survey (N=8580). Panic disorder and agoraphobia were
      assessed with the Revised Clinical Interview Schedule (CIS-R). RESULT: The
      prevalence of panic disorder with or without agoraphobia was 1.70% (95%
      confidence interval: 1.41-2.03%). Subthreshold panic was more common. Economic
      inactivity was consistently associated with all syndromes. The comorbidity
      pattern of the panic syndromes and the associated functional impairment show that
      panic-related conditions are important public health problems, even in
      subthreshold status. CONCLUSION: The findings show that efforts to reduce the
      disability associated with psychiatric disorders should include detection and
      management of panic disorder.

PMID- 20813509
TI  - In vivo potentiation of reboxetine and citalopram effect on extracellular
      noradrenaline in rat brain by alpha2-adrenoceptor antagonism.
AB  - The therapeutic activity of noradrenaline reuptake inhibitors (NaRIs) and
      serotonin reuptake inhibitors (SSRIs) as antidepressant is based on their ability
      to increase monoamine concentrations in the synaptic cleft. alpha(2)
      Adrenoceptors inhibit noradrenaline (NA) release, which modulates antidepressant
      neurochemical activity. The present study assesses the influence of the addition
      of the selective alpha(2)-adrenoceptor antagonist RS79948 to the NaRI reboxetine
      and the SSRI citalopram on brain extracellular NA. Dual-probe microdialysis
      technique in the locus coeruleus (LC) and prefrontal cortex (PFC) was performed
      in freely moving rats. Acute reboxetine (3 and 5 mg/kg i.p.) promoted a dose
      dependent increase of NA in LC (164 +/- 15%; 243 +/- 24%) and PFC (140 +/- 7%;
      181 +/- 30%). Acute citalopram (5 mg/kg i.p.) did not change NA in LC or PFC, but
      at 10 mg/kg i.p. increased NA in LC (144 +/- 14%) and decreased it in PFC (-42 +/
      7%). An inactive dose of RS79948 (0.1mg/kg i.p.) in rats pretreated with
      reboxetine (3 mg/kg i.p.) or citalopram (5mg/kg i.p.) induced a significant
      enhancement of NA in LC (reboxetine: 462 +/- 137%; citalopram: 142 +/- 11%) and
      PFC (reboxetine: 281 +/- 56%; citalopram: 130 +/- 16%). The results indicate that
      co-administration of selective alpha(2)-adrenoceptor antagonist drugs might
      improve the effects of NaRI or SSRI antidepressants by enhancing extracellular NA
      concentrations in the brain.

PMID- 20813510
TI  - Pathological gambling: relation of skin conductance response to dopaminergic
      neurotransmission and sensation-seeking.
AB  - Absent Skin Conductance Response (SCR) in pathological gambling (PG) may relate
      to dopaminergic mechanisms. We recruited equal numbers of PG subjects and healthy
      control (HC) subjects, and then tested the claim that SCR is less conditioned by
      dopaminergic activity in PG subjects. During active gambling, SCR differed in PG
      and HC subjects (P < 0.05), but positron emission tomography revealed the same
      dopamine receptor availability. However, highly sensation-seeking (HS) PG
      subjects had lower dopamine receptor availability (P < 0.0001) in the baseline,
      compared to normal sensation-seeking (NS) PG subjects. We find that HS versus NS
      controls had the same observation of significant increase of binding potential
      (BP(ND)) in high compared to normal sensation seekers. In both groups, PG and HC,
      highly sensation-seeking subjects had significant increase of receptor
      availability in striatum, compared to normally sensation-seeking subjects,
      separately (P < 0.05 and P = 0.02, respectively) and together (P < 0.0005). We
      conclude that SCR is less conditioned by dopaminergic activity in highly
      sensation-seeking subjects, regardless of PG status.

PMID- 20813511
TI  - Exposure of mice to long-light: a new animal model to study depression.
AB  - Mood disorders are highly prevalent and often difficult to treat. One of the most
      important obstacles in research on depression is the limited availability of
      reliable and valid animal models. Here we demonstrate that the exposure of mice
      to artificial daylight for 22 h per day produces a spectrum of behavioral and
      endocrine symptoms reminiscent to those seen in animal models of depression. Oral
      administration of the antidepressant imipramine has strong impact on these
      symptoms. Our results indicate that long-light exposure of mice represents a
      simple new method to study depression.

PMID- 20813512
TI  - Phenazine-1-carboxylic acid is a more important contributor to biocontrol
      Fusarium oxysporum than pyrrolnitrin in Pseudomonas fluorescens strain Psd.
AB  - Phenazines and pyrrolnitrin (Prn) are broad spectrum antibiotics, produced by
      bacteria, more so by the biocontrol strains to kill the phytopathogens in soil.
      We have studied a rhizospheric soil isolate of Pseudomonas fluorescens strain Psd
      producing both phenazine-1-carboxylic acid (PCA) and Prn. In order to study the
      contribution of these antibiotics, the phzD and prnC genes involved in PCA and
      Prn biosynthesis, were disrupted in a site-specific manner using a group II
      intron-based Targetron gene-knockout system, and gene disruption followed by
      allelic exchange through homologous recombination, respectively. The resulting
      knockout strains Psdphz122s-34 and PsdprnC::gen did not produce PCA and Prn,
      respectively. In fact, by combining these two strategies, a Psdphz122s
      34prnC::gen double mutant could also be generated. Identification and lack of PCA
      production was corroborated by HPLC/APCI-MS analysis, and TLC detection for both
      the antibiotics in these mutants. Loss of antifungal activity against the
      phytopathogenic fungus Fusarium oxysporum was observed using in vitro growth
      assays on plates or growth chamber experiments with tomato seedling on an
      artificial substrate. Based on the characterization of these gene knockout
      mutants, we propose that PCA and Prn have a major role in antifungal activity of
      strain Psd.

PMID- 20813513
TI  - Proapoptotic DR4 and DR5 signaling in cancer cells: toward clinical translation.
AB  - Proapoptotic receptor agonists (PARAs) targeting death receptors (DRs) 4 and 5
      hold promise for cancer therapy based on their selective ability to kill
      malignant versus healthy cells. Emerging clinical results have confirmed that
      DR4/5 PARAs are relatively well-tolerated and suitable for further investigation.
      Given that some cancer cell lines and models are not sensitive to PARAs, it is
      important to develop strategies to identify what specific types of tumor cells
      may be most responsive to PARA-based therapy and how to overcome apoptosis
      resistance mechanisms in tumors. Here we review the molecular and biological
      determinants of responsiveness to PARAs in cancer cells, and discuss the
      potential for predictive biomarkers and drug combination strategies to maximize
      the anti-tumor activity of these agents.

PMID- 20813514
TI  - Bridging legal and economic perspectives on interstate municipal solid waste
      disposal in the US.
AB  - Managing municipal solid waste (MSW) within and across regions is a complex
      public policy problem. One challenge regards conceptualizing precisely what
      commodity is to be managed across space and time. The US Supreme Court view is
      that waste disposal is the article of commerce per se. Some justices, however,
      have argued that while waste disposal is the article of commerce, its interstate
      flow could be impeded by states on the grounds that they have the authority to
      regulate natural resource quality within their boundaries. The argument in this
      paper is that adopting the economic theory view of the article of commerce as
      landfill space brings the majority and dissenting US Supreme Court views--and the
      resulting sides of the public policy dispute--into closer alignment. We discuss
      waste management policy tools that emerge from this closer alignment that are
      more likely to both withstand judicial scrutiny and achieve economic efficiency.

PMID- 20813516
TI  - Enhanced electrochemical oxygen reduction-based glucose sensing using glucose
      oxidase on nanodendritic poly[meso-tetrakis(2-thienyl)porphyrinato]cobalt(II)
      SWNTs composite electrodes.
AB  - The direct electrochemistry of glucose oxidase immobilized on a nanodendritic
      poly[meso-tetrakis(2-thienyl)porphyrinato]cobalt(II)-single walled carbon
      nanotube modified glassy carbon electrode (pCoTTP-SWNTs-Nafion-GOD/GCE) is
      reported. The immobilized GOD retained its activity and exhibited a surface
      controlled, reversible two-proton and two-electron transfer reaction with a fast
      heterogeneous electron transfer rate constant (ks) of 1.01 s(-1). The pCoTTP
      SWNTs-Nafion matrix also showed an extremely low peak potential of -0.2 V vs.
      Ag/AgCl and strong response with respect to oxygen reduction. This forms the
      basis for the use of the pCoTTP-SWNTs-Nafion-GOD composite as a sensing platform
      for oxygen reduction-based glucose detection. The apparent Michaelis-Menten
      constant (Km,app) was estimated to be as low as 0.98 mM. A linear range up to 1mM
      glucose with a low detection limit of 5.33 MUM (S/N=3) and a high sensitivity of
      16.57 MUA mM(-1) cm(-2) was achieved. The biosensor also shows excellent
      selectivity against 0.2 mM uric acid and ascorbic acid. These results indicate
      that the pCoTTP-SWNTs-Nafion-GOD/GCE has potential application in sensitive and
      selective glucose detection.

PMID- 20813517
TI  - Addition of low-dose morphine to intrathecal bupivacaine/sufentanil labour
      analgesia: A randomised controlled study.
AB  - BACKGROUND: Single-shot spinal analgesia with bupivacaine and a short-acting
      opioid for labour pain is popular due to its simplicity, rapid onset, and
      profound analgesia without significant motor block. Its limitation is the short
      duration of action. Supplementation with intrathecal morphine has been shown to
      prolong analgesia. We compared the addition of placebo or morphine 50 or 100 MUg
      to intrathecal bupivacaine and sufentanil to evaluate the impact on duration of
      labour analgesia. METHOD: Following ethics committee approval and verbal and
      written patient consent, 90 healthy nulliparous women were included in the study.
      As part of a combined spinal-epidural technique, women were randomised to receive
      intrathecal bupivacaine 1.25mg and sufentanil 5 MUg with morphine 50 MUg, 100 MUg
      or saline placebo in a double-blind fashion. Onset of analgesia was measured as
      the time from intrathecal injection to a visual analogue scale pain score < or =4
      (scale 0-10) and the duration of analgesia as the time from intrathecal injection
      to the return of pain >4. RESULTS: No significant differences between the groups
      were seen in onset or duration of analgesia, side effects or obstetric and
      neonatal outcome. CONCLUSION: The addition of 50 or 100 MUg morphine to 1.25mg
      bupivacaine and 5 MUg sufentanil during established labour did not significantly
      increase the duration of analgesia.

PMID- 20813518
TI  - Biodiesel production by a mixture of Candida rugosa and Rhizopus oryzae lipases
      using a supercritical carbon dioxide process.
AB  - In this study, various factors, such as temperature, pressure, agitation speed,
      water content, and the concentration and ratio of immobilized ROL and CRL were
      investigated for the efficient enzymatic production of biodiesel using a
      supercritical carbon dioxide process. Furthermore, a stepwise reaction method for
      the maintenance of immobilized lipase activity was optimized. Optimal conditions
      for biodiesel production were determined to be as follows: 130 bar pressure, 45 
      degrees C temperature, 250 rpm agitation speed, 10% water content, and 20%
      immobilized ROL and CRL (1:1). When batch process was performed under optimal
      conditions, the biodiesel conversion yield was 99.13% at 3 h. Biodiesel
      conversion yield was 99.99% at 2 h when 90 mmol methanol was used in a stepwise
      reaction. Moreover, the conversion yield of biodiesel produced by the repeated
      recycling of immobilized lipase in the stepwise reactions was 85% after 20
      reuses.

PMID- 20813519
TI  - Assessment of the influence of thermal pre-treatment time on the macromolecular
      composition and anaerobic biodegradability of sewage sludge.
AB  - Laboratory and pilot-scale experiments were carried out in order to evaluate the
      influence of thermal pre-treatment time on waste-activated sludge properties and
      anaerobic biodegradability. Six experimental conditions were analyzed from 0 to
      30 min of hydrolysis time. Solubilization of macromolecular compounds, changes in
      the main sludge properties and anaerobic biodegradability of the sewage sludge
      were evaluated. A similar carbohydrate solubilization degree was achieved, from
      53% to 70% and 59% to 75% for lab- and pilot-scale experiments, respectively. In
      the case of proteins, the values of solubilization were lower in the pilot-scale
      experiment than in the laboratory, with 31-45% and 47-70%, respectively. Ammonia
      and volatile fatty acid did not undergo important changes; however the sludge
      dewaterability enhanced at increased pre-treatment times. All the pre-treatment
      conditions had a positive effect with regard to anaerobic biodegradability and by
      fitting experimental data with a simplified mathematical model, it was concluded
      that the maximum biogas production rate is more influenced by the pre-treatment
      time than the total biogas production.

PMID- 20813520
TI  - Enhanced biomethanation of kitchen waste by different pre-treatments.
AB  - Five different pre-treatments were investigated to enhance the solubilisation and
      anaerobic biodegradability of kitchen waste (KW) in thermophilic batch and
      continuous tests. In the batch solubilisation tests, the highest and the lowest
      solubilisation efficiency were achieved with the thermo-acid and the pressure
      depressure pre-treatments, respectively. However, in the batch biodegradability
      tests, the highest cumulative biogas production was obtained with the pressure
      depressure method. In the continuous tests, the best performance in terms of an
      acceptable biogas production efficiency of 60% and stable in-reactor CODs and VFA
      concentrations corresponded to the pressure-depressure reactor, followed by
      freeze-thaw, acid, thermo-acid, thermo and control. The maximum OLR (5 g COD L(
      1) d(-1)) applied in the pressure-depressure and freeze-thaw reactors almost
      doubled the control reactor. From the overall analysis, the freeze-thaw pre
      treatment was the most profitable process with a net potential profit of around
      11.5 ? ton(-1) KW.

PMID- 20813521
TI  - Anaerobic storage as a pretreatment for enhanced biodegradability of dewatered
      sewage sludge.
AB  - Dewatered sewage sludge is often stored still before further processing and final
      disposal. This study showed that anaerobic storage of dewatered sewage sludge
      could hydrolyze organic matter from the sludge matrix, and increase soluble
      organic acid content from 90 to 2400 mg/L and soluble organic carbon content from
      220 to 1650 mg/L. Correspondingly, the contents of proteins, celluloses and
      hemicelluloses were reduced by 2-9%. Applying anaerobic storage markedly enhanced
      the efficiency of the subsequent bio-drying process on stored sludge.
      Correspondingly, biogas and odor gas were produced immediately after commencing
      the sludge storage. Anaerobic storage with odor control can be applied as a
      pretreatment process for dewatered sewage sludge in wastewater treatment plants.

PMID- 20813522
TI  - Elucidation of the active conformation of the amino terminus of receptor-bound
      secretin using intramolecular disulfide bond constraints.
AB  - Family B G protein-coupled receptors include several potentially important drug
      targets, yet our understanding of the molecular basis of ligand binding to and
      activation of these receptors is incomplete. While NMR and crystal structures
      exist for peptide ligand-associated amino-terminal domains of several family
      members, these only provide insights into the conformation of the carboxyl
      terminal region of the peptides. The amino-terminal region of these peptides,
      critical for biological activity, is believed to interact with the helical bundle
      domain, and is, therefore, unconstrained in these structures. The aim of the
      current study was to provide insights into the conformation of the amino terminus
      of secretin as bound to its receptor. We prepared a series of conformationally
      constrained secretin peptides containing intramolecular disulfide bonds that were
      predicted by molecular modeling to approximate the conformation of the analogous
      region of PACAP bound to its receptor that had been determined using transfer-NOE
      NMR techniques. Secretin peptides with pairs of cysteine residues in positions 2
      7, 3-5, 3-6, 4-7, 7-9, and 4-10 were studied as linear and disulfide-bonded
      forms. The analog with a disulfide bond connecting positions 7-9 had binding
      affinity and biological activity similar to natural secretin, supporting the
      relevance of this constraint to its active conformation. While this feature is
      shared between secretin and PACAP, absence of activity in other constrained
      peptides in this series also suggest that there are differences between these
      receptor-bound conformations. It will be critical to extend similar studies to
      other family members to learn what structural elements might be most conserved in
      this family.

PMID- 20813523
TI  - Discovery and structure-activity relationship of a novel spirocarbamate series of
      NPY Y5 antagonists.
AB  - A novel series of trans-8-aminomethyl-1-oxa-3-azaspiro[4.5]decan-2-one
      derivatives was identified with potent NPY Y5 antagonist activity. Optimization
      of the original lead furnished compounds 23p and 23u, which combine sub-nanomolar
      Y5 activity with metabolic stability, oral bioavailability, brain penetration and
      strong preclinical profile for development. Both compounds significantly
      inhibited the food intake induced by a Y5 selective agonist with minimal
      effective doses of 3mg/kg po.

PMID- 20813524
TI  - Dihydro-resveratrol--a potent dietary polyphenol.
AB  - Dihydro-resveratrol (dihydro-R), a prominent polyphenol component of red wine,
      has a profound proliferative effect on hormone-sensitive tumor cell lines such as
      breast cancer cell line MCF7. We found a significant increase in MCF7 tumor cells
      growth rates in the presence of picomolar concentrations of this compound. The
      proliferative effect of dihydro-R was not observed in cell lines that do not
      express hormone receptors (MDA-MB-231, BT-474, and K-562).

PMID- 20813525
TI  - Isothermal sensitive detection of microRNA using an autonomous DNA machine
      recycling output as input.
AB  - An autonomous DNA machine recycling the output as the input for isothermal,
      sensitive, and specific detection of miRNAs has been developed. This machine
      shows considerably high signal amplification efficiency (~1000-fold) and thus a
      low detection limit (~20 amol). The machine also shows high specificity,
      discriminating 50 amol of synthetic miRNA from 100-fold larger amounts of its
      family member and from 100 ng of unrelated total RNAs. Moreover, it is available
      for practically detecting natural miRNAs in total RNAs.

PMID- 20813526
TI  - Synthesis and biological evaluation of a novel series of bis-salicylaldehydes as
      mushroom tyrosinase inhibitors.
AB  - A series of novel bis-salicylaldehydes were synthesised and evaluated as
      tyrosinase inhibitors using a tyrosinase-dependent L-DOPA oxidation assay. The
      bis-salicylaldehydes exhibited greater inhibitory activity than salicylaldehyde.
      Our data suggests that these novel compounds may serve as a structural template
      for the design and development of novel tyrosinase inhibitors.

PMID- 20813527
TI  - Synthesis, antimicrobial, and mosquito larvicidal activity of 1-aryl-4-methyl-3,6
      bis-(5-methylisoxazol-3-yl)-2-thioxo-2,3,6,10b-tetrahydro-1H-pyrimido[5,4
      c]quinolin-5-ones.
AB  - A series of 1-aryl-4-methyl-3,6-bis-(5-methylisoxazol-3-yl)-2-thioxo-2,3,6,10b
      tetrahydro-1H-pyrimido[5,4-c]quinolin-5-ones (6a-h) have been synthesized by
      cyclization of ethyl-3-aryl-4-(2-chlorophenyl)-6-methyl-1-(5-methylisoxazol-3-yl)
      2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates 4a-h with 3-amino-5
      methylisoxazole 5. Compounds 4a-h were obtained by Biginelli reaction, by
      condensation of aromatic aldehyde 1, ethyl acetoacetate 2, and isoxazolyl
      thioureas 3 in a one-pot reaction catalyzed by ceric ammonium nitrite (CAN).
      Compounds 6a-h were tested for their antibacterial and antifungal activities
      against various bacterial and fungal strains. The results showed that these
      compounds exhibited good antibacterial and antifungal activity compared with that
      of standard antibiotics. Mosquito larvicidal activity of the newly synthesized
      compounds 6a-h is also studied against fourth instar larvae Culex
      quinquefasciatus. Some of the compounds are proved to be lethal for mosquito
      larvae.

PMID- 20813528
TI  - Novel dihydropyrimidines as a potential new class of antitubercular agents.
AB  - A small library of 30 dihydropyrimidines was synthesized and evaluated for their
      in vitro antitubercular activity against Mycobacterium tuberculosis H(37)Rv. Two
      compounds, ethyl 4-[3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl]-6-methyl-2-oxo
      1,2,3,4-tetrahydropyrimidine-5 carboxylate 4a and ethyl 4-[3-(4-nitrophenyl)-1
      phenyl-1H-pyrazol-4-yl]-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
      4d were found to be the most active compounds in vitro with MIC of 0.02 MUg/mL
      against MTB and were more potent than isoniazid.

PMID- 20813530
TI  - Footscan pressure insoles: accuracy and reliability of force and pressure
      measurements in running.
AB  - In the current investigation, the accuracy and reliability of two pairs of
      Footscan pressure insoles (500 Hz, RSscan, Belgium) was assessed, with four
      female (pair 1) and four male (pair 2) participants each performing 16 running
      trials (3.8m/s +/- 5%). Intraclass Correlation Coefficients (ICC) revealed that
      the reliability of the force and pressure data was generally excellent
      (ICC>0.75). In comparison with impact and propulsive force data collected
      simultaneously with a force plate (AMTI, 500 Hz), insole data were significantly
      lower (p<0.05). Therefore, despite the excellent reliability of measurements, the
      accuracy of the impact and propulsive forces taken with the Footscan pressure
      insole is low. It is concluded that data collected without appropriate
      calibration should be used with caution, particularly if the aim is to use the
      data for a comparison of absolute force and pressure magnitudes with criterion
      values.

PMID- 20813529
TI  - Search for influence of spatial properties on affinity at alpha1-adrenoceptor
      subtypes for phenylpiperazine derivatives of phenytoin.
AB  - A series of phenylpiperazine derivatives of phenytoin was evaluated for their
      affinity at alpha(1)-adrenoceptor subtypes in functional bioassays (rat tail
      artery: alpha(1A) and/or alpha(1B); guinea pig spleen: alpha(1B); rat aorta:
      alpha(1D)). The most potent compounds at alpha(1A)-, alpha(1B)- and alpha(1D)
      adrenoceptors, 11, 18 and 8, showed affinities in the submicromolar range. The
      role of a hydrogen bond donor group for affinity and selectivity at alpha(1B)
      adrenoceptors, postulated by Bremner's pharmacophore model, was confirmed by
      functional and molecular modelling studies.

PMID- 20813531
TI  - A new upper extremity sparing non-weight bearing orthosis.
AB  - OBJECTIVES: Axillary and forearm crutches are commonly utilized in the treatment
      of foot and ankle injuries. In order to decrease the energy expenditure during
      mobilization, to prevent upper extremity complications, and to let the upper
      extremity free for other usages, we designed a new orthosis. The study is
      conducted to compare walking energy parameters of this newly designed orthosis
      with the axillary and forearm crutches. MATERIALS AND METHODS: 10 healthy young
      male volunteers walked on treadmill with three different orthoses in randomized
      order. Oxygen expenditure, oxygen cost, rate of perceived exertion (Borg scale),
      and observer stability assessment were analyzed. RESULTS: Concerning oxygen
      consumption, perceived exertion, and observer stability assessment, the new
      device was found superior to the other devices (P<0.05). The new orthosis was
      superior to forearm crutches concerning oxygen cost (P=0.027) but not
      significantly different from the axillary crutches (P=0.062). DISCUSSION:
      Compared to frequently used orthoses, the developed device provides mobilization
      using less or similar amount of energy. Additionally it spares one upper
      extremity to be used for other activities.

PMID- 20813533
TI  - Gentisides C-K: nine new neuritogenic compounds from the traditional Chinese
      medicine Gentiana rigescens Franch.
AB  - Nine new alkyl 2,3-dihydroxybenzoates, gentisides C-K, were isolated from the
      traditional Chinese medicine Gentiana rigescens Franch. Their structures and
      stereochemistry were elucidated by spectroscopic methods, and comparison of the
      specific rotation with that of the gentiside B. These metabolites are additional
      members of the gentisides which belong to a novel class of neuritogenic
      compounds. They are structurally different from one another because they possess
      varying alkyl chain lengths, with or without an isobutyl or isopropyl group at
      the end of the alkyl chain. These compounds are potent inducers of neurite
      outgrowth on PC12 cells. The gentiside C possessing the shortest alkyl chain
      length exhibited the highest neuritogenic activity among all of the gentisides.
      Gentiside C showed a significant neuritogenic activity at 1 MUM against PC12
      cells comparable to that seen for the best nerve growth factor (NGF)
      concentration of 40 ng/mL. In addition, evident neuritogenic activity was
      observed in the cells when treated with gentiside C at a concentration as low as
      0.03 MUM. The structure-activity relationships within the gentisides A-K revealed
      that alkyl chain length is important for the activity, but structure diversity at
      the end of the alkyl chain is not.

PMID- 20813534
TI  - Synthesis, anti-fungal and 1,3-beta-D-glucan synthase inhibitory activities of
      caffeic and quinic acid derivatives.
AB  - New derivatives of caffeic acid and quinic acid were synthesized and their anti
      fungal and inhibitory activities on fungal 1,3-beta-glucan synthase were
      determined in comparison with those of the corresponding chlorogenic acid
      derivatives. All the chlorogenic, quinic and caffeic acid derivatives that were
      coupled with an H(2)N-orn-4-(octyloxy) aniline group (1, 1b and 1c) displayed
      potent activities in both anti-fungal and inhibition of 1,3-glucan synthase
      assays. Compounds 1 and 1c inhibited the fungal membrane enzyme with the potency
      comparable to that of a known 1,3-beta-D-glucan synthase inhibitor, aculeacin A.
      The results revealed that the anti-fungal activity of the chlorogenic acid
      derivative with a free amino group was at least partly due to inhibition of the
      fungal 1,3-beta-glucan synthase. These results suggest that further investigation
      on caffeic acid derivatives may lead to the discovery of novel anti-fungal agents
      with drug-like properties.

PMID- 20813532
TI  - RNA helicases at work: binding and rearranging.
AB  - RNA helicases are ubiquitous, highly conserved enzymes that participate in nearly
      all aspects of RNA metabolism. These proteins bind or remodel RNA or RNA-protein
      complexes in an ATP-dependent fashion. How RNA helicases physically perform their
      cellular tasks has been a longstanding question, but in recent years, intriguing
      models have started to link structure, mechanism and biological function for some
      RNA helicases. This review outlines our current view on major structural and
      mechanistic themes of RNA helicase function, and on emerging physical models for
      cellular roles of these enzymes.

PMID- 20813535
TI  - Identification of small molecule inhibitors of telomerase activity through
      transcriptional regulation of hTERT and calcium induction pathway in human lung
      adenocarcinoma A549 cells.
AB  - High telomerase activity (TA) is detected in most cancer cells; and thus, TA
      inhibition by drug or dietary food components is a new strategy for cancer
      prevention. In this report, we examined the effects of fourteen natural or
      synthetic compounds on TA in human lung adenocarcinoma A549 cells. The results
      demonstrated that some of the tested compounds inhibited TA, being 2'-hydroxy
      2,3,4',6'-tetramethoxychalcone (HTMC) was the most potent among tested. In A549
      cells, HTMC also inhibited the cell proliferation, decreased the expression of
      human telomerase reverse transcriptase (hTERT) and sequentially reduced the hTERT
      promoter. In soft agar assay HTMC treatment reduced the colony formation of A549
      cells. Cellular fractionation and immunofluorescence assay demonstrated that
      there was no translocation of hTERT from nuclei to cytoplasm. Further studies
      revealed that the release of Ca(2+) was the underlying mechanism of suppressed TA
      and hTERT transcription in A549 cells exposed to HTMC. These in vitro data
      support the development of HTMC as a therapeutic agent for cancer complications.

PMID- 20813536
TI  - Isolation and characterization of fluorescence-enhancing RNA tags.
AB  - Methods for the visualization of RNAs are urgently needed for studying a wide
      variety of cellular processes. Here we report on-bead screening of RNA libraries
      and its application to the isolation of specific fluorescence-enhancing RNA
      sequences. A one-bead-one-compound combinatorial RNA library with over one
      million different sequences was synthesized using the split-and-mix method. Solid
      phase synthesis of 30 mer RNAs was performed on 15MUm and 60MUm diameter
      polystyrene beads bearing a non-cleavable linker. The RNA-derivatized beads were
      incubated with the well-established FlAsH pre-fluorophore and then screened for
      fluorescence enhancement, either by manually picking the brightest beads under a
      fluorescence microscope or by sorting with a FACS instrument. A protocol was
      established for sequence determination from single beads. While numerous RNA
      sequences showed increased fluorescence when immobilized, only few of them
      influenced the fluorescence properties of the FlAsH dye when detached from the
      beads. One of these sequences was found to induce a bathochromic shift in the
      excitation (from 492 to 510nm) and emission (from 512 to 523nm) maxima. This
      shift was accompanied by a 3.6-fold fluorescence enhancement of FlAsH
      fluorescence intensity. Mutation studies on the sequence revealed a rather robust
      structural motif.

PMID- 20813537
TI  - Synthesis and biological evaluation of diastereoisomerically pure N,O
      nucleosides.
AB  - Several N,O-nucleosides have been synthesized in good yields by direct 1,3
      dipolar cyclization methodology, in the absence of solvent. A remarkable cis
      stereoselectivity (de 98%) was observed by tuning the substituents on the nitrone
      moiety. A good number of these N,O-nucleosides have been evaluated for cytotoxic
      activity against selected cellular lines. Some of the tested compounds have
      proven to be potential antiproliferative drugs.

PMID- 20813538
TI  - Trichobilharzia regenti (Digenea: Schistosomatidae): changes of body wall
      musculature during the development from miracidium to adult worm.
AB  - Trichobilharzia regenti (Schistosomatidae, Digenea), a parasite of birds,
      exhibits a unique strategy among schistosomes, having affinity to the nervous
      system of vertebrate hosts. Migration of parasitic stages within hosts and/or
      swimming of non-parasitic larvae in water environment depend on the action of
      body wall muscles which were studied with confocal and electron microscopy. In
      all stages, body wall musculature is comprised of differently organized circular
      and longitudinal muscles. During the development, an extensive change of
      musculature characteristics and/or formation of new muscle structures were
      recorded; cercariae, schistosomula and adult worms produce additional underlying
      diagonal muscle fibers and inner plexus of radial musculature. Substantial
      changes of the outer environment during penetration of a host (osmotic values of
      water vs. host tissues) are accompanied by surface transformation of
      miracidia/mother sporocysts and cercariae/schistosomula. Contrary to that,
      changes of body musculature in these stages are characterized only by growth and
      re-organization of existing structures, and never by formation of new components
      of body musculature. Future studies in this field may contribute to a better
      knowledge of morphology and function of trematode muscles, including those of
      schistosomes that are important pathogens of humans and animals.

PMID- 20813539
TI  - Rapid prototyping in craniofacial surgery: using a positioning guide after
      zygomatic osteotomy - A case report.
AB  - INTRODUCTION: The management of post-traumatic deformity in the midface region
      poses challenges for the maxillofacial surgeon. Ensuring symmetry after zygomatic
      osteotomy can be difficult and precise positioning of the osteotomised bony
      fragments requires careful treatment planning. It may be necessary to use a
      coronal flap to allow the surgeon to compare the contralateral zygomatic bone to
      allow symmetrical reduction. The authors present a new technique for the
      positioning of osteotomised zygomatic bones using a combination of computer
      assisted surgical simulation and rapid prototyping. METHOD: A patient presented
      to our unit with a post-traumatic zygomatic deformity. Using surgical simulation
      software the displaced zygomatic bone was osteotomised and placed in the ideal
      position on a three-dimensional computed tomography scan (3D CT). The position
      was determined by reference to the contralateral zygoma. In addition the
      repositioning of the soft tissues was simulated. A surgical guide which allowed
      intraoperative positioning of the osteotomised zygoma was manufactured by a rapid
      prototyping process. Use of the guide allowed a minimally invasive approach to
      the affected zygoma. The post-operative results were compared to the predicted
      outcome. RESULTS: The post-operative appearance was satisfactory and corresponded
      well with the predicted result. There was a significant reduction in operative
      time compared to the previous management of similar cases.

PMID- 20813540
TI  - Photophysical evaluation of mTHPC-loaded HSA nanoparticles as novel PDT delivery
      systems.
AB  - Controlled drug release is one of the main goals of recent developments in drug
      carrier systems. In this work human serum albumin (HSA) nanoparticles as carriers
      for 5-, 10-, 15-, 20-Tetrakis (3-hydroxyphenyl)-chlorin (mTHPC) were
      investigated. The photophysical properties of mTHPC-HSA nanoparticles in
      dependence of loading ratio and level of HSA cross-linking were determined.
      Further the drug release after uptake by Jurkat cells and in vitro singlet oxygen
      kinetics were examined. The loading ratio of the mTHPC-HSA nanoparticles turned
      out to be of major importance for the PDT relevant electronic parameters in
      solution. Therefore, only HSA nanoparticles with low mTHPC-loading ratio generate
      singlet oxygen in D(2)O. However, after cellular uptake all mTHPC-HSA samples
      generate singlet oxygen in Jurkat cells, but the decomposition rate depends on
      the level of HSA cross-linking.

PMID- 20813541
TI  - Impact of photodynamic therapy on inflammatory cells during human chronic
      periodontitis.
AB  - The aim of this study was to evaluate the effects of the photodynamic therapy
      (PDT) on the inflammatory infiltrate and on the collagen network organization in
      human advanced chronic periodontitis. Two different drug delivery systems (DDS)
      were tested (liposomes and nanoemulsions) to determine if the effects of PDT
      could differ according to the DDS used. Sixteen patients presenting two teeth
      with chronic advanced periodontitis and important tooth mobility with clinical
      indication of extraction were included in the group liposomes (group L, n=8) or
      in the group nanoemulsions (group N, n=8) in order to compare the effects of each
      DDS. Seven days before extractions one tooth of each patient was treated with PDT
      using phthalocyanine derivatives as photosensitizers and the contralateral tooth
      was taken as control. In group L the density of gingival collagen fibers (66+/
      19%) was significantly increased (p<0.02) when compared to controls (35+/-21%).
      Concerning the antigen-presenting cells, PDT had differential effects depending
      on the drug delivery system; the number of macrophages was significantly
      decreased (p<0.05) in group L while the number of Langerhans cells was
      significantly decreased in group N (p<0.02). These findings demonstrate that PDT
      presents an impact on gingival inflammatory phenomenon during chronic
      periodontitis and leads to a specific decrease of antigen-presenting cells
      populations according to the drug delivery system used.

PMID- 20813542
TI  - Survival outcomes of a salvage patient population after radioembolization of
      hepatic metastases with yttrium-90 microspheres.
AB  - PURPOSE: To determine in a retrospective study the potential benefit on survival
      outcomes of radioembolization using yttrium-90 ((90)Y) resin microspheres in a
      cohort of patients presenting with chemotherapy-refractory liver metastases,
      primarily from colorectal cancer (CRC). MATERIALS AND METHODS: Over 3 years, 249
      patients were referred to the authors' center to determine suitability for
      radioembolization as treatment for hepatic metastases. All patients were defined
      as salvage, having failed first-line and second-line chemotherapies. These
      patients were divided into group 1 (CRC) and group 2 (all other cancers, eg,
      breast, neuroendocrine) and assessed for overall survival (OS) as a whole and
      according to group. RESULTS: Using (90)Y resin microspheres, 208 patients were
      treated, undergoing 223 radioembolization treatments. The median OS was 8.3
      months for the whole cohort, 7.9 months for group 1, and 8.7 months for group 2.
      At the 3-month follow-up, there was an overall adverse event rate of 9%. At the
      end of the data collection period, 62 patients were still alive. CONCLUSIONS:
      Radioembolization shows promise as an effective and safe treatment for patients
      with chemotherapy-refractory hepatic metastases providing an extension to
      survival in the salvage setting.

PMID- 20813543
TI  - Successful treatment of aneurysmal bone cyst of the hip in a child by selective
      transcatheter arterial embolization.
AB  - Aneurysmal bone cysts are rare lesions that occur more commonly in the first and
      second decades of life. In children, a juxtaepiphyseal location is associated
      with increased risk of growth plate damage, skeletal deformity, and recurrence.
      Different treatments have been reported for the management of aneurysmal bone
      cysts, including surgical excision with or without adjuvants, intralesional
      injection of sclerosing agents, radiation therapy, cryotherapy, systemic
      calcitonin therapy, and selective arterial embolization. The authors present the
      case of a 5-year-old girl with a large aneurysmal bone cyst at the proximal
      femur, complicated by a pathologic fracture; treatment with two selective
      transcatheter arterial embolizations was curative.

PMID- 20813544
TI  - Efficiency of drug delivery to the coronary arteries in swine is dependent on the
      route of administration: assessment of luminal, intimal, and adventitial coronary
      artery and venous delivery methods.
AB  - PURPOSE: To compare the efficiency of five different drug delivery methods to the
      coronary artery in swine. MATERIALS AND METHODS: A nanoparticle-albumin-bound,
      nonradioactive isotopic marker was administered within the left anterior
      descending coronary artery (LAD) through a microinfusion catheter (MIC:
      adventitial, n = 8, and luminal, n = 4), a porous drug infusion balloon (DIB:
      intimal, n = 4), and a straight catheter (SC: luminal, n = 2) and within the
      superior vena cava (SC: intravenous, luminal, n = 2). The distribution of the
      marker in heart, lung, liver, kidney, muscle, blood, urine, and bile was
      determined 68-84 minutes after delivery. The heart was sectioned into six axial
      slices and each slice divided into four quadrants. The marker content was assayed
      by neutron bombardment and the total counts of disintegrations per minute (DPM)
      expressed as a percentage of the control for each device delivery control.
      RESULTS: After luminal delivery with the nonactuated MIC (MIC-NA) or intimal
      delivery with the DIB, 0.17% +/- 0.07 and 0.39% +/- 0.09, respectively, less than
      0.39% of the total marker was detected in the heart. After adventitial delivery
      with the actuated MIC (MIC-A), 63.1% +/- 9.9 of the total marker was detected in
      the heart. Marker was only detected in quadrants containing the coronary LAD,
      with the highest level in the middle slice and lower marker levels in consecutive
      proximal and distal heart slices. The nonactuated MIC-NA and DIB drug infusion
      balloon patterns of marker distribution were similar to those of actuated MIC-A,
      although with reduced levels. These delivery methods were also associated with
      considerably more marker detected in the lungs and liver: at least 22% compared
      with 1.34% +/- 1.34 for the actuated MIC-A There was one delivery failure with
      the actuated MIC. CONCLUSIONS: Catheter-based adventitial delivery with the MIC-A
      represents a more efficient delivery method for retention of vascular
      therapeutics.

PMID- 20813545
TI  - Reliability and validity of COOP/WONCA functional health status charts for stroke
      patients in primary care.
AB  - Dartmouth Coop Functional Health Assessment/World Organization of National
      Colleges, Academies and Academic Association of General Practitioners
      (COOP/WONCA) functional health assessment charts depict levels of function/well
      being along 5-point ordinal scales in 6 domains. Responses, illustrated by
      drawings, make these charts a suitable tool for the stroke population, given the
      high prevalence (20%) of language impairment in this population. This study
      examined the validity and reliability of COOP/WONCA charts for community-dwelling
      stroke survivors. A total of 55 participants in this cross-sectional study
      completed COOP/WONCA Charts, Hospital Anxiety and Depression Scale (HAD), Stroke
      Specific Quality of Life Scale (SSQoL), EuroQoL EQ-5D and visual analogue scale
      (VAS), International Physical Activity Questionnaire (IPAQ), and Astrand-Rhyming
      submaximal oxygen volume (VO2) fitness test. Spearman's correlation coefficient
      was used to test criterion validity, Cronbach's alpha was used to test internal
      validity, and the Mann-Whitney U tested discriminative validity. A subgroup (n =
      30) completed COOP/WONCA charts 2 days later, and test-retest reliability
      (Kendall's tau-b statistic) analysis was conducted. Good agreement was observed
      between COOP/WONCA physical fitness chart, VO2, and IPAQ (rho = -0.438, P = .001;
      rho = -0.497, P < .001), COOP/WONCA feelings chart and HAD anxiety and depression
      scores (rho = 0.498, P < .001; rho = 0.494, P < .001), COOP/WONCA overall health
      chart and EuroQol EQ-5D VAS (rho = -0.535; P < .001), and COOP/WONCA daily
      activity and social activity charts and SSQoL (rho = -0.371, P = .005; rho = 
      0.463, P < .001). Cronbach's alpha (0.72) reflected good internal consistency
      among COOP/WONCA scales. Discriminative ability for independent ambulation and
      clinical depression was demonstrated (U = 103.5, P < .001; U = 156, P = .015).
      Test-retest reliability in each domain except Changes in Health was significant
      at P < .05 (Kendall's tau-b, 0.344-0.653). Our data indicate that the COOP/WONCA
      Functional Health charts demonstrate good validity and overall reliability for
      use with stroke patients in primary care.

PMID- 20813546
TI  - High plasma D-dimer is a marker of deep vein thrombosis in acute stroke.
AB  - This study investigated whether plasma D-dimer level is useful for detection of
      deep vein thrombosis (DVT) in patients with acute stroke. A total of 133 patients
      hospitalized within 3 days after stroke onset underwent duplex venous
      ultrasonographic examination of the lower limbs and repeated measurements of
      plasma D-dimer level. DVT was detected in 36 of 100 patients with ischemic stroke
      and in 25 of 33 patients with intracerebral hemorrhage (ICH) (76%; P < .001).
      Plasma D-dimer level on admission (7.5 +/- 10.7 MUg/mL vs 3.7 +/- 10.1 MUg/mL; P
      = .040) and its maximum level before the ultrasonographic examination (29.1 +/-
      48.7 MUg/mL vs 5.5 +/- 11.0 MUg/mL; P < .001) were higher in the patients with
      DVT compared with those without DVT. On multivariate logistic regression
      analysis, the maximum D-dimer level was independently related to the
      identification of DVT (odds ratio [OR] 1.05; 95% confidence interval [CI], 1.00
      1.09 per 1-MUg/mL increase; P = .045), but the admission D-dimer level was not
      when it was included instead of the maximum D-dimer level. In addition, female
      sex (OR, 4.99), ICH (OR, 5.20), high Wells clinical score (OR, 2.40 per 1-point
      increase), and low protein level (OR, 0.21 per 1-g/dL increase) were
      independently related to the identification of DVT. The optimum cutoff value of
      the maximum D-dimer level for positive DVT was 5.5 MUg/mL (sensitivity, 89%;
      specificity, 82%). Our findings suggest that high plasma D-dimer level during the
      course of acute stroke can help detect DVT on duplex venous ultrasonography.

PMID- 20813547
TI  - Microalbuminuria, indicated by total versus immunoreactive urinary albumins, in
      acute ischemic stroke patients.
AB  - Microalbuminuria, assessed by measuring immunoreactive albumin, is common in
      patients with cerebrovascular disease and is associated with increased risk of
      stroke. Total urinary albumin (t-uAlb) comprises both immunoreactive albumin (ir
      uAlb) and nonimmunoreactive albumin (nir-uAlb). We hypothesized that t-uAlb is a
      more sensitive indicator of microalbuminuria than ir-uAlb, and that measurement
      of t-uAlb will increase the prevalence of microalbuminuria in ischemic stroke
      patients compared with measurement of ir-uAlb and will show a stronger
      correlation with the severity of stroke and oxidative stress. In urine samples
      from 98 patients with ischemic stroke, the albumin-to-creatinine ratios t
      uAlb/uCreat and ir-uAlb/uCreat were measured by high-performance liquid
      chromatography (HPLC) and immunoturbidimetry (IT), and the nir-uAlb/uCreat ratio
      was calculated. Urinary ortho-tyrosine (o-Tyr/uCreat), an indicator of oxidative
      stress, was measured by HPLC. The severity of stroke was scored based on the
      National Institutes of Health Stroke Scale (NIHSS). The prevalence of
      microalbuminuria detected by HPLC was significantly higher than that detetcted by
      IT (66.3 vs 36.7%). Although all forms of albumin showed significant correlation
      with stroke severity (t-uAlb: r = 0.24, P < .05 ir-uAlb: r = 0.25, P < .05 nir
      uAlb: r = 0.29, P < .05), only nir-uAlb was found to be an independent predictor
      of stroke severity (B = 0.20, beta = 0.35, P < .05). In addition, t-uAlb/uCreat
      and nir-uAlb/uCreat had a significant correlation with o-Tyr/uCreat (r = 0.336, P
      < .05 and r = 0.358, P < .05 respectively), whereas ir-uAlb/uCreat did not (r =
      0.22, P > .05). Our data suggest that in acute ischemic stroke patients, t-uAlb
      is a more sensitive indicator of microalbuminuria than the presently used ir
      uAlb. Future studies should aim to elucidate the underlying mechanisms for the
      relationship among urinary albumins and cerebrovascular diseases and the role of
      urinary albumins in risk stratification for stroke.

PMID- 20813548
TI  - Transesophageal echocardiography screening in subjects with a first
      cerebrovascular ischemic event.
AB  - Our goal was to develop decision guides to predict the presence of a high-risk
      source of embolus and to predict a change in management following transesophageal
      echocardiography (TEE) in subjects who present with a first cerebral ischemic
      event. We conducted a retrospective review of subjects age >=18 years who
      underwent TEE after a first ischemic event and were admitted to our stroke
      service between 2004 and 2007 (n = 287). A high-risk source of embolus and a
      change in clinical management (including medication changes or subsequent
      testing) were analyzed as separate endpoints, using multivariate techniques and
      receiver operating characteristic curves. We found that 14.3% of the subjects had
      a high-risk source, and an additional 61.3% had a potential (or low-risk) source
      of embolus. Increasing age and no history of diabetes mellitus were independently
      associated with a high-risk source of embolus. TEE would be recommended for
      nondiabetic individuals age >=66 years (sensitivity, 68%; specificity, 76%). The
      area under the curve (AUC) for detecting a high-risk source was 0.773. TEE
      results changed medications or clinical management in 30.3% of the subjects.
      Current smokers were less likely to undergo a change in management. The AUC was
      uninformative (0.56) for predicting changes in management. Subjects presenting
      with a first ischemic event age >=66 years may benefit from TEE. Although changes
      in management occurred in at least 30% of our cohort, no factors that predicted a
      change in management better than chance alone could be identified.

PMID- 20813549
TI  - Phosphorylated endothelial NOS Ser1177 via the PI3K/Akt pathway is depressed in
      the brain of stroke-prone spontaneously hypertensive rat.
AB  - Stroke-prone spontaneously hypertensive rats (SHRSP) demonstrate impaired
      endothelium-dependent relaxation and often develop brain injuries. We
      investigated whether the regulatory mechanism for endothelial NOS (eNOS)
      phosphorylation and activation is altered in the cerebral cortex of SHRSP at a
      younger age. Western blot analysis revealed a low ratio of phosphor-eNOS
      (Ser1177) to total eNOS in SHRSP at 10 weeks of age. In addition, urinary nitric
      oxide metabolites (ie, nitrate and nitrite) were decreased compared with normal
      control WKY rats. Likewise, Akt phosphorylation (especially Ser473) was
      significantly reduced, with no changes in total Akt. Furthermore, the amount of
      the phosphatidylinositol 3-kinase (PI3K) was upstream of Akt was diminished,
      although attenuation of the PI3K/Akt pathway was not an effect of mTOR, another
      downstream target of Akt. Our findings indicate that abnormalities of the
      PI3K/Akt pathway in the cerebral cortex are involved in the impaired eNOS
      phosphorylation and activation in SHRSP.

PMID- 20813550
TI  - Clinical profiles, complications, and disability in cocaine-related ischemic
      stroke.
AB  - Cocaine use is associated with ischemic stroke through unique mechanisms,
      including reversible vasospasm, drug-induced arteritis, enhanced platelet
      aggregation, cardioembolism, and hypertensive surges. To date, no study has
      described disability in patients with cocaine-related ischemic stroke. The
      present study compared risk factors, comorbidities, complications, laboratory
      findings, medications, and outcomes in patients with cocaine-related (n = 41) and
      non-cocaine-related (n = 221) ischemic stroke (n = 147) and transient ischemic
      attack (n = 115) in 3 academic hospitals. The patients with cocaine-related
      stroke were younger (mean age, 51.9 years vs 59.1 years; P = .0008) and more
      likely to be smokers (95% vs 62.9%; P < .004). The prevalence of arrhythmias was
      significantly higher in the patients with cocaine-related stroke, and that of
      diabetes was significantly higher in those with non-cocaine-related strokes. The
      prevalence of hypertension and lipid profiles were similar in the 2 groups;
      however, those with cocaine-related stroke were less likely to receive statins.
      Antiplatelet use was similar in the 2 groups. Survivors of both groups had
      similar modified Rankin scores and lengths of hospital stay. In the older urban
      population, smoking and cocaine use may coexist with other cerebrovascular risk
      factors, and cocaine-related strokes have similar morbidities and mortality as
      non-cocaine-related strokes. Moreover, because the patients with cocaine-related
      stroke is younger, they have an earlier morbidity. New strategies for effective
      stroke prevention interventions are needed in this subgroup.

PMID- 20813551
TI  - Is cognitive functioning 1 year poststroke related to quality of life domain?
AB  - Previous studies on the association between poststroke cognitive impairment and
      quality of life (QoL) have shown divergent results. In this study, we
      investigated the relationships between cognitive functioning and various QoL
      domains at 1 year poststroke. This was a cross-sectional study, examining 92
      patients at 1 year poststroke. Cognitive functioning was measured with a
      neuropsychological test battery covering language, attention and psychomotor
      function, memory, visuoperception, and neglect. QoL domains were functional
      independence (Barthel Index), social participation (Frenchay Activities Index),
      depressive mood (Center for Epidemiological Studies Depression Scale), and life
      satisfaction (Life Satisfaction Questionnaire). Bivariate and multivariate
      relationships between cognitive and QoL variables were analyzed, the latter both
      with and without controlling for demographic variables and motor impairment. The
      prevalence of cognitive impairments varied between 19.3% (neglect) and 72%
      (attention and psychomotor function). Correlations between cognitive functioning
      and QoL were strongest for social participation (0.41-0.60, P < .01) and
      functional independence (0.13-0.58, P < .05). The percentages of variance
      explained by the total cognition score were 19% for functional independence, 40%
      for participation, 8% for life satisfaction, and 5% for depression. Controlling
      for demographic factors and motor impairments resulted in negligible percentages
      of variance additionally explained by cognitive functioning. The percentages of
      explained variance were somewhat lower in the analyses with the separate
      cognitive domains and not significant for depression. Poor cognitive functioning
      was associated with reduced functional independence, social participation,
      depressive mood, and life satisfaction 1 year post; however, motor impairment was
      a stronger determinant of long-term QoL than cognitive functioning.

PMID- 20813552
TI  - Thrombolytic therapy for acute stroke in the elderly: an emergent condition in
      developing countries.
AB  - Elderly patients may represent an important group when considering new stroke
      treatments, particularly in developing countries. The aim of this study was to
      analyze the use of recombinant tissue plasminogen activator (rtPA) in elderly
      Brazilian patients with acute ischemic stroke. Clinical and neuroimaging
      parameters at admission, frequency of symptomatic intracranial hemorrhage, and
      outcome were compared between elderly (>=80 years) and nonelderly (<80 years)
      stroke patients treated with rtPA in the Porto Alegre Stroke Network. We
      evaluated 183 nonelderly patients (mean age, 63 +/- 12 years) and 55 elderly
      patients (mean age, 84 +/- 3 years). Female sex, hypertension, congestive heart
      failure, atrial fibrillation, and previous history of stroke or transient
      ischemic attack were more frequent in the elderly patients. Elderly patients also
      presented with higher mean systolic blood pressure (P = .03) and National
      Institutes of Health Stroke Scale (NIHSS) score (P < .0001), whereas the
      nonelderly patients had a higher serum glucose level (P = .03). The rate of
      symptomatic intracranial hemorrhage was 10.9% in the elderly patients and 6.6% in
      the nonelderly patients (P = .28), and a substantial proportion of the elderly
      patients achieved a favorable outcome (modified Rankin Scale score <=1) at 90
      days, although this proportion was lower than that in the nonelderly patients
      (42% vs 58%; P = .04). Poorer outcomes were generally seen in elderly patients
      with an anterior circulation stroke, a higher NIHSS score, hypoattenuation in
      >=1/3 lf the middle cerebral artery territory, and an Alberta Stroke Program
      Early CT score of <=7 on an initial computed tomography scan. Our results support
      the administration of intravenous rtPA in selected elderly stroke patients
      presenting early to the hospital in developing countries.

PMID- 20813553
TI  - Comparison of computed tomography angiography and transesophageal
      echocardiography for evaluating aortic arch disease.
AB  - Aortic arch (AA) atheroma is a common source of artery-to-artery embolism.
      Identification of AA atherosclerotic disease is an important component of the
      embolic stroke workup. Transesophageal echocardiography (TEE) is the gold
      standard for AA evaluation, but it has associated risks and is not always readily
      available. Computed tomography angiography (CTA) is a rapid and noninvasive
      alternative. This study was conducted to compare the sensitivity and specificity
      of CTA and TEE for detecting AA disease. We performed a retrospective review of
      250 consecutive patients at a tertiary stroke center who underwent both TEE and
      CTA within a 90-day period. We compared the presence and characteristics of AA
      plaques using a predetermined grading system for plaques in the ascending,
      transverse, and descending arch for both modalities (grades 1-4). Out of 750 AA
      segments (ascending, transverse, and descending AA in 250 patients), 494 were
      adequately imaged by CTA and TEE. The sensitivity of CTA in detecting grade 1-4
      AA atheromas was 53%, and the specificity was 89%. For only high-grade atheromas,
      the specificity improved to 99%, but the sensitivity decreased to 23%. The
      negative predictive value of CTA for detection of AA atheromas was 60% (range 54%
      65%) for all grades and 95% (range 92%-96%) for high-grade atheromas. CTA has a
      high negative predictive value for AA atheromas, especially for higher-grade
      atheromas, and thus may be a useful screening tool to exclude high-grade plaques,
      indicating a possible complementary role for CTA in detecting AA atheromas.

PMID- 20813554
TI  - Cerebral microbleeds and dilative remodeling of the basilar artery: a magnetic
      resonance imaging study.
AB  - This study was conducted to examine the relationship between cerebral microbleeds
      (CMBs), one of the manifestations of small-vessel diseases (SVDs), and basilar
      artery (BA) dilatation on magnetic resonance imaging (MRI). Clinical information
      and MRI images were reviewed for 149 outpatients aged 46-90 years, excluding
      those who had a previous symptomatic cerebrovascular event. CMBs were evaluated
      on T2*-weighted MRI, and BA diameters were measured as the maximal width of the
      flow void on axial T2-weighted MRI to assess dilatation. Patients were divided
      into 2 groups, with CMBs and without CMBs, and clinical information and BA
      diameters were compared between the groups. Regression analyses of the data also
      were performed. The 2 groups had significant differences in mean blood pressure
      (MBP), low-density lipoprotein (LDL) and uricemic acid levels, and BA diameter.
      Adjusted logistic regression analysis showed that MBP (odds ratio [OR], 1.059 per
      1 mm Hg; 95% confidence interval [CI], 1.019-1.101; P = .0035), LDL (OR, 0.976
      per 1 mg/dL; 95% CI, 0.960-0.994; P = .0072), and BA diameter (OR, 3.266 per 1
      mm; 95% CI, 1.504-7.103; P = .0028) each had an independent association with the
      presence of CMB. Adjusted multiple regression analysis showed that only BA
      diameter (beta coefficient, 0.240; 95% CI, 0.775-3.734; P = .0031) was
      independently associated with the number of CMBs. Our data indicate that CMB, a
      manifestation of SVD, shows a strong association with BA dilatation.

PMID- 20813555
TI  - Feasibility and effects of high-dose hypofractionated radiation therapy and
      simultaneous multi-kinase inhibition with sunitinib in progressive metastatic
      renal cell cancer.
AB  - OBJECTIVES: Radiotherapy (RT) is considered oncologically ineffective in
      metastatic renal cell cancer (mRCC). Inhibition of angiogenetic pathway may lead
      to radiosensitization in mRCC. The aim of this study was to evaluate the efficacy
      of the simultaneous combination of RT with systemic treatment of bulky (mRCC)
      using sunitinib. METHODS AND MATERIALS: We included 22 patients with progressive
      mRCC between 04/2007 and 08/2008 at the University Hospital Munich Grobetahadern.
      All patients underwent high-dose hypofractionated RT while they were
      simultaneously treated systemically with sunitinib 50 mg. RESULTS: Median age was
      63.0 years (range 26.7-84.4). Median dose of radiation was 40 Gy (range 25-50) in
      a median of 8 fractions (range 5-30). Treatment sites were brain, retroperitoneal
      and mediastinal lymph nodes, spinal cord, bones, liver, and kidney. Median follow
      up was 14.3 months. After 3 months, 2 patients had complete remission (CR), 9
      patients showed partial remission (PR) as measured by response evaluation
      criteria in solid tumors (RECIST) criteria, 2 patients had minor response (MR),
      and 8 patients had stable disease (SD). Only 1 patient did not respond to
      therapy. Toxicity was very low with only 1 grade 4 hypertension. Skin toxicities
      were manageable with no grade 3 event during the combination period. CONCLUSIONS:
      The combination of RT with simultaneous systemic treatment using sunitinib is
      effective in patients with progressive mRCC. With high dose RT, complete response
      seems to be possible. Further evaluation should be based upon combination of RT
      with systemic therapy, rather than sequential RT regiments.

PMID- 20813556
TI  - Endodontic flare-ups: a prospective study.
AB  - The objective of this prospective clinical study was to evaluate the incidence of
      flare-ups (pain and/or swelling requiring endodontic interappointment and
      emergency treatment) and identify the risk factors associated with their
      occurrence in patients who received endodontic treatment from June 2006 to June
      2007 at the endodontics clinic of the Sao Paulo Dental Association (APCD), Jardim
      Paulista branch, Sao Paulo, Brazil. The incidence of flare-ups was 1.71% out of
      408 teeth that had received endodontic therapy. Statistical analysis using the
      chi-squared test (P < .05) indicated a direct correlation between the flare-up
      rate and the presence of a periradicular radiolucency.

PMID- 20813557
TI  - Complications after mandibular distraction osteogenesis: a retrospective study of
      131 patients.
AB  - OBJECTIVES: The objectives of this study were to evaluate the occurrence and
      severity of complications after mandibular distraction osteogenesis (DO) with
      internal devices. STUDY DESIGN: The study was a retrospective analysis of 131
      patients (mean age: 16.2 years) consecutively treated by mandibular DO from 1998
      to 2009. Ninety-two patients had unilateral and 39 had bilateral distraction,
      yielding a total of 170 procedures. The mean follow-up period was 21 months.
      Severity of complications was ranked in terms of need of intervention and risk of
      a compromised outcome. RESULTS: Minor, moderate, and severe complications
      occurred in 58%, 8%, and 3% of the patients, respectively. Most minor
      complications were related to device activation or temporary hypesthesia.
      Moderate complications often related to hardware, whereas severe complications
      occurred in 4 patients with sensory deficit or temporomandibular joint problems.
      CONCLUSIONS: Although minor complications were frequent, they did not compromise
      treatment outcome, so mandibular DO is considered a safe method for correction of
      mandibular deformities. Moreover, some of the complications could be prevented by
      proper precautions.

PMID- 20813558
TI  - Oral presentation of malignant mesothelioma.
AB  - We report a case of metastatic mesothelioma presenting as an oral metastasis in a
      46-year-old patient. The patient presented with 2 polypoid lesions that appeared
      to be benign on the dorsum of the tongue. Excisional biopsy showed the presence
      of metastatic carcinoma that on further investigation proved to be mesothelioma.
      The initial presentation of mesothelioma as an oral metastasis is not previously
      reported. This article highlights the importance of biopsy and histopathological
      diagnosis in presumed benign lesions and the role of the general dental
      practitioner in screening for oral neoplasms.

PMID- 20813559
TI  - CAD/CAM surface templates as an alternative to the intermediate wafer in
      orthognathic surgery.
AB  - OBJECTIVE: A new simple technique using a pair of surface templates fabricated by
      CAD/CAM technique as an alternative to the use of intermediate surgical wafer is
      presented. STUDY DESIGN: A patient with transverse maxillary cant and maxillary
      midline deviation was scanned using computed tomography (CT) to create a 3D model
      of the maxillofacial bone. Eight virtual cylindrical markers were placed on the
      selected locations of maxilla. Subsequently, the locations of these cylinders
      were expressed as drill holes in the preosteotomy templates. The maxillary
      segment was separated and repositioned in the computer according to preoperative
      plans. Postosteotomy surface templates were then designed and resin templates
      were fabricated by a rapid prototyping machine. After investing and casting,
      metal templates were fabricated. At the beginning of operation, surgical fixation
      holes on the maxilla were drilled with the preosteotomy templates. Once maxillary
      osteotomy and segmentation were finished, screws were placed through the holes in
      the postosteotomy templates into the predrilled holes on the bone
      correspondingly, and maxillary segments were fixed with the titanium plates.
      RESULTS: After the postosteotomy templates were positioned and fixed, the
      maxillary segment was placed to the desired position. Maxillary transverse cant
      and midline deviation were corrected as the preoperative plan and simulation.
      CONCLUSION: The use of the surface templates before and after osteotomy as an
      alternative to intermediate wafer in orthognathic surgery can minimize labor and
      errors contained in the traditional way, reducing preoperative work as well as a
      reduction in operation time.

PMID- 20813560
TI  - Transcription factor osterix modified bone marrow mesenchymal stem cells enhance
      callus formation during distraction osteogenesis.
AB  - This study was designed to investigate the effects of local delivery of bone
      marrow mesenchymal stem cells (BMMSCs) with or without osterix (OSX) gene
      transfected on bone regeneration in the distracted zone using a rabbit model of
      mandibular lengthening. Fifty-four New Zealand white rabbits underwent
      osteodistraction of the left mandible and were then randomly divided into group
      A, group B, and group C (n = 18 for each group). At the end of distraction BMMSCs
      transfected with OSX, autologous BMMSCs and physiological saline were injected
      into the distraction gaps in groups A, B, and C, respectively. Nine animals from
      each group were humanely killed at 2 and 6 weeks after completion of distraction.
      The distracted mandibles were harvested and processed for radiographic,
      histological, and immunohistochemical examination. Excellent bone formation in
      the distracted callus was observed in group A and group B; the former showed
      better bone formation and highest bone mineral density (BMD), thickness of new
      trabeculae (TNT, mm) and volumes of the newly formed bone area (NBV) in the
      distraction zones. Group C animals showed poor bone formation in the distracted
      callus when compared with groups A and B. Positive immunostaining of bone
      sialoprotein (BSP) was observed in the distracted callus in all groups; however,
      BSP expression was much stronger in group A than in groups B and C. The results
      of this study suggest transplantation of BMMSCs can promote bone formation in DO;
      OSX-mediated ex vivo gene therapy was more effective during bone deposition and
      callus formation in distraction osteogenesis.

PMID- 20813561
TI  - Influence of chemical irrigants on the tensile bond strength of an adhesive
      system used to cement glass fiber posts to root dentin.
AB  - OBJECTIVE: The aim of this study was to evaluate the influence of endodontic
      irrigants on the tensile bond strength of an adhesive system used to cement glass
      fiber posts to dentin. STUDY DESIGN: Fifty bovine roots were divided into 5
      groups according to the solution used during instrumentation: G1, 0.9% NaCl
      (control); G2, 1.0% NaOCl; G3, 2.5% NaOCl; G4, 5.25% NaOCl; G5, 2% chlorhexidine
      gel + 0.9% NaCl. The root canals were obturated with gutta-percha and AH Plus
      sealer, and the glass fiber posts were cemented with Clearfil SE Bond/RelyX ARC.
      The specimens were submitted to tensile strength testing and the results were
      analyzed by analysis of variance. RESULTS: There were no statistically
      significant differences regarding the irrigant solution factor (P > .70).
      CONCLUSION: It was concluded that the different irrigant solutions did not affect
      the tensile bond strength of the fixation system used to cement the
      intraradicular glass fiber posts to dentin.

PMID- 20813562
TI  - Mutational analyses of the BRAF, KRAS, and PIK3CA genes in oral squamous cell
      carcinoma.
AB  - OBJECTIVES: The development of oral squamous cell carcinoma (OSCC) is a complex,
      multistep process. To date, numerous oncogenes and tumor-suppressor genes have
      been implicated in oral carcinogenesis. Of particular interest in this regard are
      genes involved in cell cycling and apoptosis, such BRAF, KRAS, and PIK3CA genes.
      STUDY DESIGN: Mutations of BRAF, KRAS, and PIK3CA were evaluated by direct
      genomic sequencing of exons 1 of KRAS, 11 and 15 of BRAF, and 9 and 20 of PIK3CA
      in OSCC specimens. RESULTS: Both BRAF and KRAS mutations were detected with a
      mutation frequency of 2% (1/42). PIK3CA mutations were detected at 3% (1/35).
      CONCLUSIONS: This is the first report implicating BRAF mutation in OSCC. Our
      study supports that mutations in the BRAF, KRAS, and PIK3CA genes make at least a
      minor contribution to OSCC tumorigenesis, and pathway-specific therapies
      targeting these 2 pathways should be considered for OSCC in a subset of patients
      with these mutations.

PMID- 20813563
TI  - Donor site morbidity using the buccinator myomucosal island flap.
AB  - OBJECTIVE: The objective of this study was to analyze our experience with donor
      site morbidity after harvesting a buccinator myomucosal island flap (BUMIF) for
      reconstructing surgical defects involving the tongue and floor of the mouth after
      oncological resections in 15 consecutive patients. STUDY DESIGN: Donor site
      morbidity was evaluated using 5 parameters: mouth opening, oral commissure
      symmetry, inner vestibule restoration, cheek mucosal lining, and the esthetic
      result. The clinical evaluation was performed by a blinded panel of 2 clinicians
      and the patient him- or herself, assessing each parameter with a score ranging
      from 0 to 3. The 3 scores for each parameter were summed to obtain a score
      reflecting the overall parameter assessment. RESULTS: The mean mouth opening
      score was 8.6 out of a maximum of 9 (range, 6-9). The mean commissure symmetry
      was 8.6 (range, 7-9), the mean inferior vestibule score was 8 (range, 6-9), the
      mean cheek lining score was 8.2 (range, 7-9), and the mean final esthetic score
      was 8.5 (range, 6-9). CONCLUSION: The results of this retrospective evaluation
      demonstrate that when special care is taken in the management of the BUMIF donor
      site, its morbidity is extremely low, allowing optimal functional and cosmetic
      results and confirming the major role of this flap in reconstructing moderate
      size defects following tongue and floor of the mouth resections.

PMID- 20813564
TI  - A new topical treatment protocol for oral hairy leukoplakia.
AB  - OBJECTIVE: The aim of this study was to present a new topical treatment protocol
      for oral hairy leukoplakia (OHL), consisting of a 25% podophyllin resin with a 1%
      penciclovir cream (PP), and to compare this topical treatment protocol's efficacy
      with that of 2 other topical treatment protocols: a 25% podophyllin resin (P) and
      a 25% podophyllin resin with a 5% acyclovir cream (PA). STUDY DESIGN: Forty-two
      human immunodeficiency virus-positive patients with 69 OHL lesions were randomly
      treated using P, PA, or PP (14 patients in each topical treatment protocol).
      Clinical healing was determined when the white plaque could no longer be seen in
      the primary location of the lesion. Topical treatment performance was evaluated
      by clinical healing within each week of topical treatment protocol as well as by
      the recurrence of the lesion. Statistical survival analysis was performed using a
      Cox proportional hazards model. RESULTS: Approximately 55% of the patients
      presented with clinical healing of OHL within 7-8 weeks of each topical treatment
      protocol. After the sixth week, the PA treatment protocol presented a faster
      clinical healing rate of OHL. Recurrence was observed in 3 and 7 OHL lesions
      treated with P and PP treatment protocols, respectively. CONCLUSIONS: The PP
      treatment protocol proved to be effective; however, the PA treatment protocol was
      more effective in the clinical healing rate for OHL than P and PP after the sixth
      week of treatment, and no recurrent OHL was observed in the PA treatment group.

PMID- 20813565
TI  - The relation of C-reactive protein to vasoocclusive crisis in children with
      sickle cell disease.
AB  - In view of evidence linking sickle cell anemia (SCA) with chronic inflammation,
      and given the role of high sensitivity C-reactive protein (hs-CRP) as
      inflammatory mediator, we hypothesized that SCA vasoocclusive crisis (VOC) is
      associated with heightened hs-CRP levels. Study subjects comprised 104 SCA
      patients who experienced VOC event during the study period (VOC group), and 40
      SCA patients who did not develop VOC for at least 9 months prior to blood
      collection (Steady-state group). hs-CRP determination was done by latex-enhanced
      nephelometry. Higher hs-CRP levels were seen in VOC [median(range)=31.3(1.14
      363.0)] than steady-state [median(range)=5(0.16-185.0)] groups (P<0.001), with
      enrichment in high hs-CRP percentiles in VOC cases, which translated into step
      wise increased VOC risk. Receiver-operating characteristic (ROC) analysis was
      employed in assessing the usefulness of hs-CRP as predictor of the frequency and
      severity of VOC. Spearman's correlation coefficient between hs-CRP and VOC was
      0.65 (P<0.001) among unselected patients (0.71 in males and 0.59 in females). hs
      CRP area under ROC curves was 0.90 (95% CI=0.85-0.94) among unselected patients,
      0.94 (95% CI=0.89-0.98) for males, and 0.85 (95% CI=0.77-0.93) for females.
      Logistic regression analysis confirmed the positive association of increased hs
      CRP levels with VOC, which correlated positively with VOC frequency (P<0.001),
      type (P<0.001), pain (P<0.001), and need for hospitalization (P=0.024). These
      data support strong association of increased hs-CRP levels with VOC, which
      impacts VOC-related parameters, and support a role for hs-CRP in VOC follow-up.

PMID- 20813566
TI  - Novel adenoviruses and herpesviruses detected in bats.
AB  - Samples from native Hungarian or captive bats were tested by PCR for the presence
      of adenoviruses and herpesviruses. Two novel adenoviruses from a common noctule
      (Nyctalus noctula) and a greater horseshoe (Rhinolophus ferrum-equinum) bat were
      detected. In captive Egyptian fruit bats (Rousettus aegyptiacus), DNA from two
      novel herpesviruses was demonstrated. Phylogenetic analysis facilitated
      provisional taxonomic placement of the newly detected viruses. Such analysis and
      the existence of unique, shared early proteins (E3 and E4) suggest that canine
      adenoviruses may have originated in vespertilinoid bats.

PMID- 20813567
TI  - Panayiotopoulos syndrome: probable genetic origin, but not in SCN1A.
AB  - Panayiotopoulos syndrome is encompassed in the classification of the ILAE in
      idiopathic focal epilepsies. Mutations in the SCN1A gene have been associated
      with the development of this syndrome. We present two cases of Panayiotopoulos
      syndrome in two monozygotic twins, who underwent a molecular analysis of SCN1A,
      but no alteration was found. These cases suggest a genetic origin, and SCN1A
      appears to be associated with the outcome but not with the development of this
      syndrome.

PMID- 20813568
TI  - Gastrointestinal symptoms in type-1 diabetes: is it all about brain plasticity?
AB  - BACKGROUND AND AIMS: Autonomic neuropathy seems to play a central role in the
      development of gastrointestinal symptoms in diabetes. In order to explore the
      neuronal mechanisms behind the symptoms we evaluated the brain processing of
      painful visceral stimuli. METHODS: Evoked brain potentials were recorded to
      assess the response to painful oesophageal electrical stimuli in 15 healthy
      volunteers and 14 type-1 diabetes patients with autonomic neuropathy and related
      gastrointestinal symptoms. Source reconstruction analysis (fixed Multiple Signal
      Classification (MUSIC) algorithm) was applied to estimate the location of the
      evoked electrical activity in the brain. RESULTS: The patients had increased
      oesophageal sensory thresholds compared to the controls (P=0.004). The latencies
      of the evoked brain potentials at vertex (Cz) were increased (P=0.007) and
      amplitudes reduced (P=0.011) in diabetics. Compared with controls the patients
      had a posterior shift of the electrical sources in the anterior cingulate cortex
      at 54 ms, and additional sources close to the posterior insula at 95 ms and in
      medial frontal gyrus at 184 ms. CONCLUSIONS: There is evidence of altered central
      processing to visceral stimulation, and both peripheral and central mechanisms
      seem involved. Central neuronal reorganisation may contribute to our
      understanding of the gastrointestinal symptoms in patients with diabetic
      autonomic neuropathy and this may guide development and evaluation of new
      treatment modalities.

PMID- 20813569
TI  - Sodium inversion recovery MRI of the knee joint in vivo at 7T.
AB  - The loss of proteoglycans (PG) in the articular cartilage is an early signature
      of osteoarthritis (OA). The ensuing changes in the fixed charge density in the
      cartilage can be directly linked to sodium concentration via charge balance.
      Sodium ions in the knee joint appear in two pools: in the synovial fluids or
      joint effusion where the ions are in free motion and bound within the cartilage
      tissue where the Na(+) ions have a restricted motion. The ions in these two
      compartments have therefore different T1 and T2 relaxation times. The purpose of
      this study is to demonstrate the feasibility of a fluid-suppressed 3D ultrashort
      TE radial sodium sequence by implementing an inversion recovery (IR) preparation
      of the magnetization at 7T. This method could allow a more accurate and more
      sensitive quantification of loss of PG in patients with OA. It is shown that
      adiabatic pulses offer significantly improved performance in terms of robustness
      to B1 and B0 inhomogeneities when compared to the hard pulse sequence. Power
      deposition considerations further pose a limit to the RF inversion power, and we
      demonstrate in simulations and experiments how a practical compromise can be
      struck between clean suppression of fluid signals and power deposition levels.
      Two IR sequences with different types of inversion pulses (a rectangular pulse
      and an adiabatic pulse) were tested on a liquid phantom, ex vivo on a human knee
      cadaver and then in vivo on five healthy volunteers, with a (Nyquist) resolution
      of ~3.6 mm and a signal-to-noise ratio of ~30 in cartilage without IR and ~20
      with IR. Due to specific absorption rate limitations, the total acquisition time
      was ~17 min for the 3D radial sequence without inversion or with the rectangular
      IR, and 24:30 min for the adiabatic IR sequence. It is shown that the adiabatic
      IR sequence generates a more uniform fluid suppression over the whole sample than
      the rectangular IR sequence.

PMID- 20813570
TI  - Atomic hydrogen as high-precision field standard for high-field EPR.
AB  - We introduce atomic hydrogen trapped in an octaisobutylsilsesquioxane nanocage
      (H@iBuT8) as a new molecular high-precision magnetic field standard for high
      field EPR spectroscopy of organic radicals and other systems with signals around
      g=2. Its solid-state EPR spectrum consists of two 0.2 mT wide lines separated by
      about 51 mT and centered at g~2. The isotropic g factor is 2.00294(3) and
      essentially temperature independent. The isotropic 1H hyperfine coupling constant
      is 1416.8(2) MHz below 70 K and decreases slightly with increasing temperature to
      1413.7(1) MHz at room temperature. The spectrum of the standard does not overlap
      with those of most organic radicals, and it can be easily prepared and is stable
      at room temperature.

PMID- 20813573
TI  - ["The FFER 15 years after": 15th congress of the Federation francaise d'etude de
      la reproduction].

PMID- 20813572
TI  - Subcutaneous infection of a cat by Colletotrichum species.
AB  - A 13-year-old, domestic shorthair cat was presented for evaluation of a right
      tarsal mass. Physical examination revealed a 5 cm * 5 cm * 5 cm, soft, fluctuant,
      subcutaneous tarsal mass. Thoracic radiographs revealed several discrete lung
      parenchymal lesions. Abdominal ultrasound revealed abnormal architecture to both
      kidneys. Fungal culture and sensitivity from the subcutaneous mass revealed a
      uniform growth of Colletotrichum species that was susceptible to itraconazole.
      Colletotrichum species infection was confirmed in the subcutis and suspected to
      be disseminated. Colletotrichum species fungal infections in cats have not been
      previously documented.

PMID- 20813571
TI  - Prolonged hypoxia modulates platelet activating factor receptor-mediated
      responses by fetal ovine pulmonary vascular smooth muscle cells.
AB  - Hypoxia augments PAF receptor (PAFr) binding and PAFr protein expression in
      venous SMC (SMC-PV). We compared effect of acute and prolonged hypoxia (pO(2)<40
      torr) on PAFr-mediated responses in arterial SMC (SMC-PA) and SMC-PV. Cells were
      studied for 30 min (acute) or for 48 h (prolonged) hypoxia and compared to
      normoxic (pO(2) ~100 torr) conditions. PAF binding was quantified in fmol/10(6)
      cells (mean +/- SEM). PAF binding in normoxia were SMC-PA, 5.2 +/- 0.2 and in SMC
      PV, 19.3 +/- 1.1; values in acute hypoxia were SMC-PA, 7.7 +/- 0.4 and in SMC-PV,
      27.8 +/- 1.7. Prolonged hypoxia produced 6-fold increase in binding in SMC-PA,
      but only 2-fold increase in SMC-PV, but binding in SMC-PV was still higher. Acute
      hypoxia augmented inositol phosphate release by 50% and 40% in SMC-PA and SMC-PV,
      respectively. During normoxia, PAFr mRNA expression by both cell types was
      similar, but expression in hypoxia by SMC-PA was greater. In SMC-PA, hypoxia and
      PAF augmented intracellular calcium flux. Re-exposure of cells to 30 min normoxia
      after 48 h hypoxia decreased binding by 45-60%, suggesting immediate down
      regulation of hypoxia-induced PAFr-mediated effects. We speculate that re
      oxygenation immediately reverses hypoxia effect probably due to oxygen tension
      dependent reversibility of PAFr activation and suggest that exposure of the
      neonate to prolonged state of hypoxia will vilify oxygen exchange capacity of the
      neonatal lungs.

PMID- 20813574
TI  - Genetic variation of 15 autosomal microsatellite loci in a Tamil population from
      Tamil Nadu, Southern India.
AB  - The genetic profiles for 15 autosomal microsatellite loci were analyzed in a
      Tamil population from Southern India to study the genetic diversities and
      relatedness of this population with other national and global populations.
      Statistical analyses of the data revealed all loci were within Hardy-Weinberg
      Equilibrium (HWE) expectations with the exception of the locus D5S818 (p=0.011).
      A significantly greater inter-individual variation (Fst=99%) observed within the
      individuals among the four subgroups in this study and low population
      differentiation (Fst=1%) suggests relative genetic closeness of these four
      subgroups. This indicates that the populations in the southern region of India
      might have a common ancestry or probably experienced high gene flow during the
      period of their coexistence. The Neighbor Joining tree derived from genetic
      distances of samples from this study and other national and global populations
      show clustering of all the Indian populations in one branch of the tree while the
      African and Middle Eastern populations cluster in a separate branch. Principal Co
      ordinate Analysis of the genetic distance data show clustering similar to the NJ
      tree.

PMID- 20813575
TI  - On how much one can take: relocating exploitation and exclusion within the
      broader framework of allostatic load theory.

PMID- 20813576
TI  - Standardized manual palpation of myofascial trigger points in relation to
      neck/shoulder pain; the influence of clinical experience on inter-examiner
      reproducibility.
AB  - A diagnosis of Myofascial Pain Syndrome (MPS) requires palpation for the
      identification of at least one clinically relevant trigger point (TP). However,
      few comparable, high quality studies currently exist from which to draw firm
      conclusions regarding the robustness of TP examination. An inter-observer
      agreement study was conducted using two experienced and two inexperienced
      clinicians. All performed standardized palpation of the upper Trapezius
      musculature, judging the clinical relevance of TP(s) using clinician global
      assessment (GA). A random case mix of 81 female participants was examined, 14
      asymptomatic and the remainder suffering from neck/shoulder pain. Examiners
      received psychomotor skills training and video feedback analysis to improve
      protocol standardization. Kappa co-efficient calculations indicated good
      agreement between the experienced pairing (kappa = 0.63), moderate agreement
      between the mixed pairings (kappa = 0.35 and 0.47) and poor agreement between the
      inexperienced pairing (kappa = 0.22). Inter-observer agreement was not stable
      with the experienced pairing exhibiting a sharp decline in agreement during the
      latter portion of the study. Identification of clinically relevant TPs of the
      upper Trapezius musculature is reproducible when performed by two experienced
      clinicians, however, a mixed observer pairing can yield acceptable agreement. A
      protracted period of data collection may be detrimental to inter-observer
      agreement; more investigation is needed in this regard.

PMID- 20813577
TI  - The effectiveness of thoracic manipulation on patients with chronic mechanical
      neck pain - a randomized controlled trial.
AB  - The aim of our study was to assess the effectiveness of thoracic manipulation
      (TM) on patients with chronic neck pain. 120 patients aged between 18 and 55 were
      randomly allocated into two groups: an experimental group which received TM and a
      control group without the manipulative procedure. Both groups received infrared
      radiation therapy (IRR) and a standard set of educational material. TM and IRR
      were given twice weekly for 8 sessions. Outcome measures included craniovertebral
      angle (CV angle), neck pain (Numeric Pain Rating Scale; NPRS), neck disability
      (Northwick Park Neck Disability Questionnaire; NPQ), health-related quality of
      life status (SF36 Questionnaire) and neck mobility. These outcome measures were
      assessed immediately after 8 sessions of treatment, 3-months and at a 6-month
      follow-up. Patients that received TM showed significantly greater improvement in
      pain intensity (p = 0.043), CV angle (p = 0.049), NPQ (p = 0.018), neck flexion
      (p = 0.005), and the Physical Component Score (PCS) of the SF36 Questionnaire (p
      = 0.002) than the control group immediately post-intervention. All these
      improvements were maintained at the 6-month follow-ups. This study shows that TM
      was effective in reducing neck pain, improving dysfunction and neck posture and
      neck range of motion (ROM) for patients with chronic mechanical neck pain up to a
      half-year post-treatment.

PMID- 20813578
TI  - Life in the balance: a signaling network controlling survival of flooding.
AB  - Recent reports on responses to flooding, submergence, and low-oxygen stress have
      connected components in an essential regulatory network that underlies plasticity
      in growth and metabolism essential for the survival of distinct flooding regimes.
      Here, we discuss growth under severe oxygen-limited conditions (anaerobic growth)
      and less oxygen-deficient underwater conditions (ethylene-driven underwater
      growth). Low-oxygen stress causes an energy and carbohydrate crisis that must be
      controlled through regulated consumption of carbohydrates and energy reserves. In
      rice (Oryza sativa L.), low-oxygen stress, energy homeostasis and growth are
      connected by a calcineurin B-like interacting binding kinase (CIPK) in seeds
      germinated under water. In shoots, two opposing adaptive strategies to
      submergence, elongation (escape) and inhibition of elongation (quiescence), are
      controlled by related ethylene response factor (ERF) DNA binding proteins that
      act downstream of ethylene and modulate gibberellin-mediated shoot growth.
      Increased resolution of the flooding signaling network will require more precise
      investigation of the interactions between oxygen tension and cellular energy
      status in regulation of anaerobic metabolism and ethylene-driven growth, both
      essential to survival in variable flooding environments.

PMID- 20813579
TI  - Salts of aromatic amines: crystal structures, spectroscopic and non-linear
      optical properties.
AB  - Crystal structures, spectroscopic and NLO properties of 8 novel organic salts
      with aromatic amines, i.e. tyrammonium iodide (1), tyrammonium benzene-1,2,4
      tricarboxilate (2), octopammonium 5-sulfosalicylate monohydrate (3),
      octopammonium hydrogen squarate (4), dopammonium 5-sulfosalicylate dihydrate (5),
      ephedrinium mandelate (6), dopammonium hydrogen squarate (7) and bis(ephedrinium)
      squarate (8) are reported and discussed with a view of their application in
      optical technologies. The conformations of the cations of the aromatic amines are
      discussed comparing the experimental and theoretical data.

PMID- 20813581
TI  - Sleep-wake habits in Spanish primary school children.
AB  - INTRODUCTION: Sleep deficit in children has been associated with psychological
      and behavioral health alterations as well as an increased incidence of obesity
      and accidents. Several studies have assessed the effects of poor sleep patterns
      on adolescents and young adults; however few studies have been conducted in
      children and pre-teenagers. The main objective of this study was to examine sleep
      habits in primary school children. METHODS: The parents of primary school
      children in Alcoy (Spain) kept a sleep diary for their children for 1 week.
      Parents were asked to record the time their children went to bed, woke up and got
      out of bed, as well as sleep latency and total sleep time on school days and
      weekends. The data were analyzed and differences according to grade and gender
      were noted. RESULTS: Three hundred twenty-one sleep diaries were studied; 53%
      were from boys and 47% from girls. As grade increased, children went to bed later
      and slept less (p<0.001). Children slept more hours on weekend than during the
      week. There was a substantial gender difference at the highest grade level: girls
      slept 23min more than boys on weekends (p<0.001). Sleep latency was greater than
      20min in 19% of children, primarily in girls 10-12 years of age. There were a
      considerable percentage of children in each group who slept less than average for
      their age. CONCLUSION: Sleep patterns in primary school children have been
      underreported. There appears to be insufficient sleep and delayed sleep-phase
      patterns among pre-teenagers.

PMID- 20813580
TI  - Aerobic exercise improves self-reported sleep and quality of life in older adults
      with insomnia.
AB  - OBJECTIVE: To assess the efficacy of moderate aerobic physical activity with
      sleep hygiene education to improve sleep, mood and quality of life in older
      adults with chronic insomnia. METHODS: Seventeen sedentary adults aged >or=55
      years with insomnia (mean age 61.6 [SD+/-4.3] years; 16 female) participated in a
      randomized controlled trial comparing 16 weeks of aerobic physical activity plus
      sleep hygiene to non-physical activity plus sleep hygiene. Eligibility included
      primary insomnia for at least 3 months, habitual sleep duration <6.5h and a
      Pittsburgh Sleep Quality Index (PSQI) score >5. Outcomes included sleep quality,
      mood and quality of life questionnaires (PSQI, Epworth Sleepiness Scale [ESS],
      Short-form 36 [SF-36], Center for Epidemiological Studies Depression Scale [CES
      D]). RESULTS: The physical activity group improved in sleep quality on the global
      PSQI (p<.0001), sleep latency (p=.049), sleep duration (p=.04), daytime
      dysfunction (p=.027), and sleep efficiency (p=.036) PSQI sub-scores compared to
      the control group. The physical activity group also had reductions in depressive
      symptoms (p=.044), daytime sleepiness (p=.02) and improvements in vitality
      (p=.017) compared to baseline scores. CONCLUSION: Aerobic physical activity with
      sleep hygiene education is an effective treatment approach to improve sleep
      quality, mood and quality of life in older adults with chronic insomnia.

PMID- 20813582
TI  - Childhood contributions to adult sleep problems.

PMID- 20813583
TI  - Rotigotine transdermal patch in moderate to severe idiopathic restless legs
      syndrome: a randomized, placebo-controlled polysomnographic study.
AB  - OBJECTIVE: To assess the efficacy of rotigotine transdermal patch in subjects
      with moderate to severe idiopathic restless legs syndrome (RLS) and periodic limb
      movement (PLM) in sleep in a double-blind, randomized, placebo-controlled,
      multicenter study (NCT00275236). METHODS: Sixty-seven (46 rotigotine, 21 placebo)
      subjects applied rotigotine (maximum 3mg/24h) or placebo patches once-daily
      during a 4-week maintenance period; efficacy evaluations used polysomnographic
      measures and clinician/patient ratings. RESULTS: Mean PLM index (PLMI; PLM/h time
      in bed) decreased more with rotigotine (50.9/h to 8.1/h) than with placebo
      (37.4/h to 27.1/h; adjusted treatment ratio 4.25 (95% CI [2.48,7.28], p<0.0001).
      PLM during sleep with arousal index (PLMSAI; 8.57/h to 2.47/h under rotigotine,
      6.5/h to 4.95/h under placebo; adjusted treatment difference: -3.12 (95% CI [
      5.36, -0.88], p=0.0072) also improved more under rotigotine. At end of
      maintenance, 39% of rotigotine subjects had PLMI levels <5/h and 26% showed no
      RLS symptoms (IRLS=0), whereas no placebo subject met these criteria. Common drug
      related adverse events for rotigotine and placebo included nausea (21.7%/4.8%),
      headache (17.4%/14.3%), application site reactions (17.4%/4.8%), and somnolence
      (10.9%/9.5%); most were mild to moderate in intensity. CONCLUSIONS: Rotigotine
      transdermal patch was efficacious and well tolerated in the short-term treatment
      of RLS motor symptoms and associated sleep disturbances.

PMID- 20813584
TI  - Comparison of outcome in Jehovah's Witness patients in cardiac surgery: an
      Australian experience.
AB  - INTRODUCTION: Despite the advances in modern medicine, cardiac surgery remains
      associated with significant amounts of blood transfusion and is responsible for
      nearly 20% of all transfusions in Australasia. Progressive advances in perfusion
      technology and perioperative supportive management have made it possible for
      members of the Jehovah's Witnesses (JW) religious group to undergo open cardiac
      operations with remarkable safety. This study systematically compares the
      operative mortality and early clinical outcome after cardiac surgery in JWs.
      METHODS AND MATERIALS: Data was obtained from the cardiac surgery and intensive
      care unit databases from January 2002 to December 2005. A total of 5353 patients
      who underwent cardiac surgical procedures including coronary artery bypass
      grafting with cardiopulmonary bypass (n=4041) and valvular heart surgery (n=2287)
      were assessed in this study. Of the 5353 patients 49 patients refused blood and
      blood products because of their religious beliefs. Models were constructed to
      determine the association between JWs and non-JWs and three outcomes: (1)
      operative mortality, (2) postoperative variables and (3) length of stay in
      intensive care unit. Propensity scores were computed from these models and used
      to match JWs with non-JWs. RESULTS: There were minimal differences in the
      baseline patient demographic characteristics between the two groups. Haemoglobin
      and haematocrit levels were higher in JWs both before (13.7g/dL vs 12.8g/dL;
      P=0.01, and 40.0% vs 39.2%; P=0.08) and after (10.8g/dL vs 9.9g/dL; P=.003, and
      34.0% vs 30.9%; P=.001) surgery. Jehovah's Witnesses experienced significantly
      less bleeding, almost half compared to the control group, with P<0.001. No
      differences were found in the adjusted and unadjusted operative mortality or
      intensive care unit and postoperative length of stay between the two groups.
      CONCLUSION: This study concurs with the international published data that
      outcomes for JW patients who undergo cardiac surgery are similar to those who
      receive transfusion. Every appropriate opportunity to reduce the use of
      allogeneic blood products.

PMID- 20813585
TI  - Are we ready for universal genetic screening?

PMID- 20813586
TI  - Scale-up of diagnostics for multidrug resistant tuberculosis.

PMID- 20813587
TI  - Microscopic-observation drug susceptibility and thin layer agar assays for the
      detection of drug resistant tuberculosis: a systematic review and meta-analysis.
AB  - BACKGROUND: Simple, rapid, and affordable tests are needed to detect drug
      resistance in Mycobacterium tuberculosis. We did a systematic review and meta
      analysis to investigate the accuracy of microscopic-observation drug
      susceptibility (MODS) and thin layer agar (TLA) assays for rapid screening of
      patients at risk of drug-resistant tuberculosis. METHODS: In accordance with
      protocols and methods recommended by the Cochrane Diagnostic Test Accuracy
      Working Group, we systematically searched PubMed, Embase, and Biosis for reports
      published between January, 1990, and February, 2009. We included studies
      investigating detection of drug resistance in M tuberculosis with the MODS or TLA
      assay, and in which an accepted reference standard was used. Data extracted from
      the studies were combined by use of bivariate random-effects regression models
      and hierarchical summary receiver operating characteristic curves to estimate
      sensitivity and specificity for detection of resistance to specific drugs.
      FINDINGS: We identified 12 studies, of which nine investigated the MODS assay and
      three investigated the TLA assay. For the MODS assay of rifampicin resistance,
      pooled estimates were 98.0% (95% CI 94.5-99.3) for sensitivity and 99.4% (95.7
      99.9) for specificity. For the MODS assay of isoniazid resistance with a 0.1
      MUg/mL cutoff, pooled sensitivity was 97.7% (94.4-99.1) and pooled specificity
      was 95.8% (88.1-98.6), but with a 0.4 MUg/mL cutoff, sensitivity decreased to
      90.0% (84.5-93.7) and specificity increased to 98.6% (96.9-99.4). All assessments
      of rifampicin and isoniazid resistance with the TLA assay yielded 100% accuracy.
      Mean turnaround time was 9.9 days (95% CI 4.1-15.8) for the MODS assay and 11.1
      days (10.1-12.0) for the TLA assay. INTERPRETATION: MODS and TLA assays are
      inexpensive, rapid alternatives to conventional methods for drug susceptibility
      testing of M tuberculosis. Our data and expert opinion informed WHO's
      recommendation for use of selected non-commercial drug susceptibility tests,
      including MODS, as an interim solution until capacity for genotypic or automated
      liquid culture drug susceptibility testing is developed. FUNDING: Stop TB
      Department of WHO.

PMID- 20813588
TI  - Quality of life in cardiovascular disease: what is it and why and how should we
      measure it?

PMID- 20813589
TI  - Assets, challenges, and the potential of technology for nutrition education in
      rural communities.
AB  - OBJECTIVE: To examine assets of and challenges to getting adequate nutrition and
      physical activity among low-income rural residents, and the potential for
      technology to provide health education. METHODS: Environmental scans and
      community stakeholder interviews were conducted in 5 rural counties in Maryland.
      During environmental scans, stakeholders guided tours around each county to
      explore community services and resources for nutrition, physical activity and
      technology. In-depth interviews with stakeholders (n=58) focused on nutrition,
      physical activity, and technology issues. RESULTS: Low-income residents both
      benefit from and face challenges in rural settings. Besides attitude and
      knowledge barriers, lack of affordable resources and public transportation
      contributed to inattention to nutrition and physical activity. Stakeholders'
      reactions to a proposed Internet-based intervention were mostly favorable, but
      questions emerged about providing computers and Internet to individual families.
      CONCLUSIONS AND IMPLICATIONS: Internet-based education may be a viable option to
      help low-income rural residents overcome barriers to nutrition and physical
      activity.

PMID- 20813590
TI  - Orexin links emotional stress to autonomic functions.
AB  - We studied autonomic functions in orexin-deficient mice and found abnormalities
      in the emotional state-dependent adjustment of the central autonomic regulation
      on circulation and respiration. These are summarized as follows. 1) Orexin
      deficient mice exposed to a stressor exhibited an attenuated fight-or-flight
      response, including increases in respiration and blood pressure and stress
      induced analgesia. 2) Stimulation to the amygdala (AMG) or the bed nucleus of the
      stria terminalis (BNST), both of which are implicated in the stress-induced
      autonomic responses, induced long-lasting cardiorespiratory excitation in wild
      type mice but not in the orexin neuron-ablated mice. Hence, it is likely that the
      orexin system is one of the essential modulators required for orchestrating the
      neural circuits controlling autonomic functions and emotional behaviors.

PMID- 20813591
TI  - Impedance spectroscopy and conductometric biosensing for probing catalase
      reaction with cyanide as ligand and inhibitor.
AB  - In this work, a new biosensor was prepared through immobilization of bovine liver
      catalase in a photoreticulated poly (vinyl alcohol) membrane at the surface of a
      conductometric transducer. This biosensor was used to study the kinetics of
      catalase-H(2)0(2) reaction and its inhibition by cyanide. Immobilized catalase
      exhibited a Michaelis-Menten behaviour at low H(2)0(2) concentrations (<100mM)
      with apparent constant K(M)(app)=84+/-3mM and maximal initial velocity
      V(M)(app)=13.4MUS min(-1). Inhibition by cyanide was found to be non-competitive
      and inhibition binding constant K(i) was 13.9+/-0.3MUM. The decrease of the
      biosensor response by increasing cyanide concentration was linear up to 50MUM,
      with a cyanide detection limit of 6MUM. In parallel, electrochemical
      characteristics of the catalase/PVA biomembrane and its interaction with cyanide
      were studied by cyclic voltammetry and impedance spectroscopy. Addition of the
      biomembrane onto the gold electrodes induced a significant increase of the
      interfacial polarization resistance R(P). On the contrary, cyanide binding
      resulted in a decrease of Rp proportional to KCN concentration in the 4 to 50MUM
      range. Inhibition coefficient I(50) calculated by this powerful label-free and
      substrate-free technique (24.3MUM) was in good agreement with that determined
      from the substrate-dependent conductometric biosensor (24.9MUM).

PMID- 20813592
TI  - Stable interactions between DNA polymerase delta catalytic and structural
      subunits are essential for efficient DNA repair.
AB  - Eukaryotic DNA polymerase delta (Pol delta) activity is crucial for chromosome
      replication and DNA repair and thus, plays an essential role in genome stability.
      In Saccharomyces cerevisiae, Pol delta is a heterotrimeric complex composed of
      the catalytic subunit Pol3, the structural B subunit Pol31, and Pol32, an
      additional auxiliary subunit. Pol3 interacts with Pol31 thanks to its C-terminal
      domain (CTD) and this interaction is of functional importance both in DNA
      replication and DNA repair. Interestingly, deletion of the last four C-terminal
      Pol3 residues, LSKW, in the pol3-ct mutant does not affect DNA replication but
      leads to defects in homologous recombination and in break-induced replication
      (BIR) repair pathways. The defect associated with pol3-ct could result from a
      defective interaction between Pol delta and a protein involved in recombination.
      However, we show that the LSKW motif is required for the interaction between Pol3
      C-terminal end and Pol31. This loss of interaction is relevant in vivo since we
      found that pol3-ct confers HU sensitivity on its own and synthetic lethality with
      a POL32 deletion. Moreover, pol3-ct shows genetic interactions, both suppression
      and synthetic lethality, with POL31 mutant alleles. Structural analyses indicate
      that the B subunit of Pol delta displays a major conserved region at its surface
      and that pol31 alleles interacting with pol3-ct, correspond to substitutions of
      Pol31 amino acids that are situated in this particular region. Superimposition of
      our Pol31 model on the 3D architecture of the phylogenetically related DNA
      polymerase alpha (Pol alpha) suggests that Pol3 CTD interacts with the conserved
      region of Pol31, thus providing a molecular basis to understand the defects
      associated with pol3-ct. Taken together, our data highlight a stringent
      dependence on Pol delta complex stability in DNA repair.

PMID- 20813593
TI  - Determination of cefazedone in human plasma by high performance liquid
      chromatography-tandem mass spectrometry: Application to a pharmacokinetic study
      on Chinese volunteers.
AB  - A rapid, sensitive and simple high performance liquid chromatography-tandem mass
      spectrometry (HPLC-MS/MS) method was developed for determination of cefazedone in
      human plasma using metronidazole as internal standard (IS). The chromatographic
      separation was achieved on an Ultimate XB-CN column (2.1mm*150mm, 5MUm) with an
      isocratic mobile phase of acetonitrile and 20mM ammonium acetate in 0.1% formic
      acid in water (15:85, v/v). Detection was performed using electrospray ionization
      in positive ion multiple reaction-monitoring mode (SRM), monitoring the
      transitions m/z 548.2->344.1 for cefazedone and m/z 172.2->128.1 for IS.
      Calibration curves were linear over a wide range of 0.20-401.12MUg/mL for
      cefazedone in plasma. The lower limit of quantification (LLOQ) was 0.20MUg/mL.
      The intra- and inter-day precisions were less than 7.2%. The average recovery of
      cefazedone was 90.8-91.0%. The validated method was successfully applied to the
      pharmacokinetic study of cefazedone in Chinese healthy volunteers following
      intravenous (IV) administration of 500, 1000 and 2000mg cefazedone injection.

PMID- 20813594
TI  - [Recommendations and management of type I hereditary or hepatorenal tyrosinemia].
AB  - Tyrosinemia type I is a potentially lethal disease if not diagnosed and treated
      properly. Diagnostic and therapeutic advances in recent years have significantly
      improved the prognosis for these patients. It is therefore important that the
      pediatrician has a clinical practice guideline with recommendations for diagnosis
      and treatment of this disease that leads to the appropriate intervention.

PMID- 20813595
TI  - [Can residents acquire skills without compromising patient safety? The example of
      central venous catheterization].

PMID- 20813596
TI  - [Rendu-Osler-Weber syndrome: an rare cause of hypoxemia in children].
AB  - Hereditary haemorrhagic telangiectasia or Rendu-Osler-Weber syndrome is a rare
      genetic autosomic dominant disorder with an estimated prevalence of one in 3000
      5000 individuals. This multisystemic vascular dysplasia is determined by the
      mutation of two main genes which are endoglin (ENG) or HHT1 and ALK1 or HHT2.
      These mutations induce the vascular disorders which cause recurrent epistaxis and
      eventually multiple telangiectasias and arteriovenous visceral malformations
      (AVM). We report the case of an 11-year-old boy who developed severe hypoxaemia
      due to multiple pulmonary arteriovenous malformations.

PMID- 20813597
TI  - [Fungal peritonitis after gastrointestinal perforation secondary to
      cardiopulmonary resuscitation].

PMID- 20813598
TI  - [Sturge-Weber syndrome].

PMID- 20813599
TI  - [Importance of clinical pharmacology in paediatrics].

PMID- 20813600
TI  - Elements of male body image: Prediction of depression, eating pathology and
      social sensitivity among gay men.
AB  - The aim of the current study was to assess the relative uniqueness of three
      components of male body image (i.e., muscle, body fat, and height
      dissatisfaction) in the prediction of indices of psychological distress (i.e.,
      depression, eating restraint, eating concerns, and social sensitivity) among a
      community sample of 228 gay men. Results indicated that body fat dissatisfaction
      was predictive of all four criterion variables (controlling for muscle
      dissatisfaction). Conversely, muscle dissatisfaction was only associated with
      social sensitivity, while height dissatisfaction failed to significantly predict
      any of the criterion variables. These findings highlight the relative importance
      of body fat dissatisfaction among gay men and suggest that researchers and
      clinicians working with this population should utilize measures which include
      assessment of both muscularity and body fat.

PMID- 20813601
TI  - IL6 and the human limbal stem cell niche: a mediator of epithelial-stromal
      interaction.
AB  - The corneal epithelium is maintained by the limbal epithelial stem cells (LESCs).
      In this study, an in vitro model is proposed for the investigation of cell-cell
      interactions involving LESC maintenance. Imaging of the limbal niche demonstrated
      close spatial arrangement between basal limbal epithelial cells within putative
      LESC niche structures and fibroblasts in the stroma. Interactions of the human
      limbal epithelial (HLE) cells and mitotically active human limbal fibroblasts
      (HLF) were studied for the first time in a serum-free in vitro model that
      simulated aspects of the limbal niche microenvironment. HLE cocultured in a ratio
      3:1 with HLF exhibited enhanced expression of the putative stem cell markers
      ABCG2 and p63alpha and holoclones were preserved as shown by colony-forming
      efficiency assays, clonal analysis, and colony characterisation. Interleukin 6
      (IL6) was found to be up-regulated in the 3.1SF system when compared to the HLE
      culture with growth-arrested fibroblasts and serum (gold standard system, GS).
      IL6 caused a time-dependent phosphorylation of STAT3 in HLE cells. STAT3 and IL6
      inhibition in 3.1SF cultures significantly reduced HLE colony-forming efficiency,
      suggesting a previously undetected STAT3-mediated involvement of IL6 in the
      maintenance of HLE cells in a progenitor-like state.

PMID- 20813602
TI  - Upper extremity Mycobacterium marinum infection.
AB  - Mycobacterium marinum is the cause of opportunistic infections in man. Although
      its clinical presentation is usually cutaneous, osteoarticular infections are not
      rare and should be rapidly diagnosed. Orthopaedic surgeons may have to manage a
      patient with this mycobacterial infection and should be able to make this
      diagnosis based on information about the patient's history and clinical criteria.
      Lesions develop from a skin wound, with a single nodule or a bright purplish-red
      patch with papules; they also may be inflamed or may abscess. Secondary lesions
      may develop as the disease progresses. Aquatic exposure is the most important
      factor to look for. We report three cases of this infection with a delayed
      diagnosis. Response to treatment and an absence of complications are correlated
      with an early diagnosis.

PMID- 20813620
TI  - Lymph node dissection for thyroid cancer.

PMID- 20813622
TI  - Oncoplastic conservative treatment for breast cancer. Part 1: generalities and
      techniques for the external quadrants.

PMID- 20813621
TI  - Visceral surgery and pregnancy.
AB  - With an incidence of 950,000 pregnancies per year in France, the likelihood of
      seeing one or more surgical abdominal diseases during pregnancy is high. The goal
      of this update was to describe the management of four different settings in the
      pregnant woman: colorectal cancer, laparoscopic surgery, gastrointestinal
      emergency surgery, and bariatric surgery.

PMID- 20813623
TI  - [Odontogenic vulvar abscess].

PMID- 20813624
TI  - A patient-adaptive profiling scheme for ECG beat classification.
AB  - Recent trends in clinical and telemedicine applications highly demand automation
      in electrocardiogram (ECG) signal processing and heart beat classification. A
      patient-adaptive cardiac profiling scheme using repetition-detection concept is
      proposed in this paper. We first employ an efficient wavelet-based beat-detection
      mechanism to extract precise fiducial ECG points. Then, we implement a novel
      local ECG beat classifier to profile each patient's normal cardiac behavior. ECG
      morphologies vary from person to person and even for each person, it can vary
      over time depending on the person's physical condition and/or environment. Having
      such profile is essential for various diagnosis (e.g., arrhythmia) purposes. One
      application of such profiling scheme is to automatically raise an early warning
      flag for the abnormal cardiac behavior of any individual. Our extensive
      experimental results on the MIT-BIH arrhythmia database show that our technique
      can detect the beats with 99.59% accuracy and can identify abnormalities with a
      high classification accuracy of 97.42%.

PMID- 20813625
TI  - Personalization algorithm for real-time activity recognition using PDA, wireless
      motion bands, and binary decision tree.
AB  - Inactive and sedentary lifestyle is a major problem in many industrialized
      countries today. Automatic recognition of type of physical activity can be used
      to show the user the distribution of his daily activities and to motivate him
      into more active lifestyle. In this study, an automatic activity-recognition
      system consisting of wireless motion bands and a PDA is evaluated. The system
      classifies raw sensor data into activity types online. It uses a decision tree
      classifier, which has low computational cost and low battery consumption. The
      classifier parameters can be personalized online by performing a short bout of an
      activity and by telling the system which activity is being performed. Data were
      collected with seven volunteers during five everyday activities: lying,
      sitting/standing, walking, running, and cycling. The online system can detect
      these activities with overall 86.6% accuracy and with 94.0% accuracy after
      classifier personalization.

PMID- 20813626
TI  - Medical case retrieval from a committee of decision trees.
AB  - A novel content-based information retrieval framework, designed to cover several
      medical applications, is presented in this paper. The presented framework allows
      the retrieval of possibly incomplete medical cases consisting of several images
      together with semantic information. It relies on a committee of decision trees,
      decision support tools well suited to process this type of information. In our
      proposed framework, images are characterized by their digital content. It was
      applied to two heterogeneous medical datasets for computer-aided diagnoses: a
      diabetic retinopathy follow-up dataset (DRD) and a mammography-screening dataset
      (DDSM). Measure of precision among the top five retrieved results of 0.788 + or -
      0.137 and 0.869 + or - 0.161 was obtained on DRD and DDSM, respectively. On DRD,
      for instance, it increases by half the retrieval of single images.

PMID- 20813627
TI  - Feature-space-based FMRI analysis using the optimal linear transformation.
AB  - The optimal linear transformation (OLT), an image analysis technique of feature
      space, was first presented in the field of MRI. This paper proposes a method of
      extending OLT from MRI to functional MRI (fMRI) to improve the activation
      detection performance over conventional approaches of fMRI analysis. In this
      method, first, ideal hemodynamic response time series for different stimuli were
      generated by convolving the theoretical hemodynamic response model with the
      stimulus timing. Second, constructing hypothetical signature vectors for
      different activity patterns of interest by virtue of the ideal hemodynamic
      responses, OLT was used to extract features of fMRI data. The resultant feature
      space had particular geometric clustering properties. It was then classified into
      different groups, each pertaining to an activity pattern of interest; the applied
      signature vector for each group was obtained by averaging. Third, using the
      applied signature vectors, OLT was applied again to generate fMRI composite
      images with high SNRs for the desired activity patterns. Simulations and a
      blocked fMRI experiment were employed for the method to be verified and compared
      with the general linear model (GLM)-based analysis. The simulation studies and
      the experimental results indicated the superiority of the proposed method over
      the GLM-based analysis in detecting brain activities.

PMID- 20813628
TI  - Independent component analysis for auditory evoked potentials and cochlear
      implant artifact estimation.
AB  - Auditory evoked potential (AEP) recordings have been analyzed through independent
      component analysis (ICA) in the literature; however, the performance varies
      depending on the ICA algorithms used. There are very few studies that concentrate
      on the optimum parameter selection for estimating the AEP components reliably,
      while also recovering the specific artifact generated with the normal functioning
      of a cochlear implant (CI). The objective of this research is to determine which
      ICA algorithm, high-order statistics (HOS)-based or second-order statistic (SOS)
      based, is more plausible to remove this artifact and estimate the AEP. The
      optimal parameters of three such ICA algorithms for estimating the components
      from a database of recordings were determined, and then the estimates for the AEP
      and CI artifact were compared using each method. All the algorithms estimate the
      CI artifact reasonably well, although only one SOS algorithm is better positioned
      to estimate the AEP; this is primarily because it uses the temporal structure of
      this signal as part of the ICA process.

PMID- 20813629
TI  - A classification tree approach for cardiac ischemia detection using
      spatiotemporal information from three standard ECG leads.
AB  - The accurate noninvasive diagnosis of cardiac ischemia remains a great challenge.
      To this end, the ECG is the main source of information, and personal health
      systems may now embed intelligence for enabling any citizen to self-record an ECG
      anywhere at any time. Our objective is to find a decision-support approach that
      makes best use of these resources. A new classification tree based on conditions
      combinations competition (T-3C) is proposed for building a multibranch tree of
      combined decision rules, and its performance is compared to usual methods based
      either on discriminant analysis or on classification trees. Moreover, we assessed
      with these methods, the diagnosis content for ischemia detection of the
      spatiotemporal ECG information that can be retrieved either from the standard 12
      lead ECG or from only the three orthogonal leads subset (I, II, and V2), easy to
      set-up in self-care. The diagnostic accuracy of 14 decision-making strategies was
      compared for ischemia detection induced by angioplasty on a test set from a study
      population of 90 patients. The best performance is obtained with the T-3C
      algorithm on three-lead ECG, reaching 98% of sensitivity and of specificity, thus
      exceeding 23% of the diagnostic accuracy of the recommended and currently used
      standard ECG criteria.

PMID- 20813630
TI  - Extended noninvasive fetal monitoring by detailed analysis of data measured with
      phonocardiography.
AB  - This paper presents a complex heuristic method for the evaluation of fetal heart
      sounds, applying simultaneously several algorithms, where the autocorrelation
      technique has been completed with the wavelet transform and the matching pursuit
      methods. In this way, a more reliable heart rate variability can be achieved and
      further parameters of the cardiac operation can be assessed in addition to the
      conventional cardiotocographic examination. This also comprises those parameters,
      which can be investigated only with long-term or continuous monitoring, and
      those, which rely on a very accurate estimation of the heart rate variability.
      The proposed method provides a way for assessing fetal heart murmurs, which is a
      completely new possibility for monitoring the well-being of the fetus.

PMID- 20813631
TI  - Chest pulse-wave velocity: a novel approach to assess arterial stiffness.
AB  - Pulse-wave velocity (PWV) is considered as the gold-standard method to assess
      arterial stiffness, an independent predictor of cardiovascular morbidity and
      mortality. Current available devices that measure PWV need to be operated by
      skilled medical staff, thus, reducing the potential use of PWV in the ambulatory
      setting. In this paper, we present a new technique allowing continuous,
      unsupervised measurements of pulse transit times (PTT) in central arteries by
      means of a chest sensor. This technique relies on measuring the propagation time
      of pressure pulses from their genesis in the left ventricle to their later
      arrival at the cutaneous vasculature on the sternum. Combined thoracic impedance
      cardiography and phonocardiography are used to detect the opening of the aortic
      valve, from which a pre-ejection period (PEP) value is estimated. Multichannel
      reflective photoplethysmography at the sternum is used to detect the distal pulse
      arrival time (PAT). A PTT value is then calculated as PTT = PAT - PEP. After
      optimizing the parameters of the chest PTT calculation algorithm on a nine
      subject cohort, a prospective validation study involving 31 normo- and
      hypertensive subjects was performed. 1/chest PTT correlated very well with the
      COMPLIOR carotid to femoral PWV (r = 0.88, p < 10 (-9)). Finally, an empirical
      method to map chest PTT values onto chest PWV values is explored.

PMID- 20813632
TI  - Volumetric in vivo imaging of microvascular perfusion within the intact cochlea
      in mice using ultra-high sensitive optical microangiography.
AB  - Studying the inner ear microvascular dynamics is extremely important to
      understand the cochlear function and to further advance the diagnosis,
      prevention, and treatment of many otologic disorders. However, there is currently
      no effective imaging tool available that is able to access the blood flow within
      the intact cochlea. In this paper, we report the use of an ultrahigh sensitive
      optical micro-angiography (UHS-OMAG) imaging system to image 3-D microvascular
      perfusion within the intact cochlea in living mice. The UHS-OMAG image system
      used in this study is based on spectral domain optical coherence tomography,
      which uses a broadband light source centered at 1300 nm with an imaging rate of
      47[Formula: see text] 000 A-scans/s, capable of acquiring high-resolution B scans
      at 300 frames/s. The technique is sensitive enough to image very slow blood flow
      velocities, such as those found in capillary networks. The 3-D imaging
      acquisition time for a whole cochlea is  ~ 4.1 s. We demonstrate that volumetric
      reconstruction of microvascular flow obtained by UHS-OMAG provides a
      comprehensive perfusion map of several regions of the cochlea, including the otic
      capsule, the stria vascularis of the apical and middle turns and the radiating
      arterioles that emanate from the modiolus.

PMID- 20813633
TI  - On combining computer-aided detection systems.
AB  - Computer-aided detection (CAD) is increasingly used in clinical practice and for
      many applications a multitude of CAD systems have been developed. In practice,
      CAD systems have different strengths and weaknesses and it is therefore
      interesting to consider their combination. In this paper, we present generic
      methods to combine multiple CAD systems and investigate what kind of performance
      increase can be expected. Experimental results are presented using data from the
      ANODE09 and ROC09 online CAD challenges for the detection of pulmonary nodules in
      computed tomography scans and red lesions in retinal images, respectively. For
      both applications, combination results in a large and significant increase in
      performance when compared to the best individual CAD system.

PMID- 20813634
TI  - An imaging model incorporating ultrasonic transducer properties for three
      dimensional optoacoustic tomography.
AB  - Optoacoustic tomography (OAT) is a hybrid imaging modality that combines the
      advantages of optical and ultrasound imaging. Most existing reconstruction
      algorithms for OAT assume that the ultrasound transducers employed to record the
      measurement data are point-like. When transducers with large detecting areas
      and/or compact measurement geometries are utilized, this assumption can result in
      conspicuous image blurring and distortions in the reconstructed images. In this
      work, a new OAT imaging model that incorporates the spatial and temporal
      responses of an ultrasound transducer is introduced. A discrete form of the
      imaging model is implemented and its numerical properties are investigated. We
      demonstrate that use of the imaging model in an iterative reconstruction method
      can improve the spatial resolution of the optoacoustic images as compared to
      those reconstructed assuming point-like ultrasound transducers.

PMID- 20813636
TI  - A nonconservative Lagrangian framework for statistical fluid registration-SAFIRA.
AB  - In this paper, we used a nonconservative Lagrangian mechanics approach to
      formulate a new statistical algorithm for fluid registration of 3-D brain images.
      This algorithm is named SAFIRA, acronym for statistically-assisted fluid image
      registration algorithm. A nonstatistical version of this algorithm was
      implemented , where the deformation was regularized by penalizing deviations from
      a zero rate of strain. In , the terms regularizing the deformation included the
      covariance of the deformation matrices (Sigma) and the vector fields (q) . Here,
      we used a Lagrangian framework to reformulate this algorithm, showing that the
      regularizing terms essentially allow nonconservative work to occur during the
      flow. Given 3-D brain images from a group of subjects, vector fields and their
      corresponding deformation matrices are computed in a first round of registrations
      using the nonstatistical implementation. Covariance matrices for both the
      deformation matrices and the vector fields are then obtained and incorporated
      (separately or jointly) in the nonconservative terms, creating four versions of
      SAFIRA. We evaluated and compared our algorithms' performance on 92 3-D brain
      scans from healthy monozygotic and dizygotic twins; 2-D validations are also
      shown for corpus callosum shapes delineated at midline in the same subjects.
      After preliminary tests to demonstrate each method, we compared their detection
      power using tensor-based morphometry (TBM), a technique to analyze local
      volumetric differences in brain structure. We compared the accuracy of each
      algorithm variant using various statistical metrics derived from the images and
      deformation fields. All these tests were also run with a traditional fluid
      method, which has been quite widely used in TBM studies. The versions
      incorporating vector-based empirical statistics on brain variation were
      consistently more accurate than their counterparts, when used for automated
      volumetric quantification in new brain images. This suggests the advantages of
      this approach for large-scale neuroimaging studies.

PMID- 20813637
TI  - Continuous attractors of Lotka-Volterra recurrent neural networks with infinite
      neurons.
AB  - Continuous attractors of Lotka-Volterra recurrent neural networks (LV RNNs) with
      infinite neurons are studied in this brief. A continuous attractor is a
      collection of connected equilibria, and it has been recognized as a suitable
      model for describing the encoding of continuous stimuli in neural networks. The
      existence of the continuous attractors depends on many factors such as the
      connectivity and the external inputs of the network. A continuous attractor can
      be stable or unstable. It is shown in this brief that a LV RNN can possess
      multiple continuous attractors if the synaptic connections and the external
      inputs are Gussian-like in shape. Moreover, both stable and unstable continuous
      attractors can coexist in a network. Explicit expressions of the continuous
      attractors are calculated. Simulations are employed to illustrate the theory.

PMID- 20813635
TI  - MR water quantitative priors improves the accuracy of optical breast imaging.
AB  - Magnetic resonance (MR) guided optical breast imaging is a promising modality to
      improve the specificity of breast imaging, because it provides high-resolution
      quantitative maps of total hemoglobin, oxygen saturation, water content, and
      optical scattering. These properties have been shown to distinguish malignant
      from benign lesions. However, the optical detection hardware required for deep
      tissue imaging has poor spectral sensitivity which limits accurate water
      quantification; this reduces the accuracy of hemoglobin quantification. We
      present a methodology to improve optical quantification by utilizing the ability
      of Dixon MR imaging to quantitatively estimate water and fat; this technique
      effectively reduces optical crosstalk between water and oxyhemoglobin. The
      techniques described in this paper reduce hemoglobin quantification error by as
      much as 38%, as shown in a numerical phantom, and an experimental phantom. Error
      is reduced by as much 20% when imperfect MR water quantification is given. These
      techniques may also increase contrast between diseased and normal tissue, as
      shown in breast tissue in vivo. It is also shown that using these techniques may
      permit fewer wavelengths to be used with similar quantitative accuracy, enabling
      higher temporal resolution. In addition, it is shown that these techniques can
      improve the ability of MRI to quantify water in the presence of bias in the Dixon
      water/fat separation.

PMID- 20813638
TI  - Fuzzy wavelet neural network models for prediction and identification of
      dynamical systems.
AB  - This paper presents fuzzy wavelet neural network (FWNN) models for prediction and
      identification of nonlinear dynamical systems. The proposed FWNN models are
      obtained from the traditional Takagi-Sugeno-Kang fuzzy system by replacing the
      THEN part of fuzzy rules with wavelet basis functions that have the ability to
      localize both in time and frequency domains. The first and last model use
      summation and multiplication of dilated and translated versions of single
      dimensional wavelet basis functions, respectively, and in the second model, THEN
      parts of the rules consist of radial function of wavelets. Gaussian type of
      activation functions are used in IF part of the fuzzy rules. A fast gradient
      based training algorithm, i.e., the Broyden-Fletcher-Goldfarb-Shanno method, is
      used to find the optimal values for unknown parameters of the FWNN models.
      Simulation examples are also given to compare the effectiveness of the models
      with the other known methods in the literature. According to simulation results,
      we see that the proposed FWNN models have impressive generalization ability.

PMID- 20813640
TI  - An optimal data hiding scheme with tree-based parity check.
AB  - Reducing distortion between the cover object and the stego object is an important
      issue for steganography. The tree-based parity check method is very efficient for
      hiding a message on image data due to its simplicity. Based on this approach, we
      propose a majority vote strategy that results in least distortion for finding a
      stego object. The lower embedding efficiency of our method is better than that of
      previous works when the hidden message length is relatively large.

PMID- 20813639
TI  - Behavior-constrained support vector machines for fMRI data analysis.
AB  - Statistical learning methods are emerging as a valuable tool for decoding
      information from neural imaging data. The noisy signal and the limited number of
      training patterns that are typically recorded from functional brain imaging
      experiments pose a challenge for the application of statistical learning methods
      in the analysis of brain data. To overcome this difficulty, we propose using
      prior knowledge based on the behavioral performance of human observers to enhance
      the training of support vector machines (SVMs). We collect behavioral responses
      from human observers performing a categorization task during functional magnetic
      resonance imaging scanning. We use the psychometric function generated based on
      the observers behavioral choices as a distance constraint for training an SVM. We
      call this method behavior-constrained SVM (BCSVM). Our findings confirm that
      BCSVM outperforms SVM consistently.

PMID- 20813641
TI  - The sparse matrix transform for covariance estimation and analysis of high
      dimensional signals.
AB  - Covariance estimation for high dimensional signals is a classically difficult
      problem in statistical signal analysis and machine learning. In this paper, we
      propose a maximum likelihood (ML) approach to covariance estimation, which
      employs a novel non-linear sparsity constraint. More specifically, the covariance
      is constrained to have an eigen decomposition which can be represented as a
      sparse matrix transform (SMT). The SMT is formed by a product of pairwise
      coordinate rotations known as Givens rotations. Using this framework, the
      covariance can be efficiently estimated using greedy optimization of the log
      likelihood function, and the number of Givens rotations can be efficiently
      computed using a cross-validation procedure. The resulting estimator is generally
      positive definite and well-conditioned, even when the sample size is limited.
      Experiments on a combination of simulated data, standard hyperspectral data, and
      face image sets show that the SMT-based covariance estimates are consistently
      more accurate than both traditional shrinkage estimates and recently proposed
      graphical lasso estimates for a variety of different classes and sample sizes. An
      important property of the new covariance estimate is that it naturally yields a
      fast implementation of the estimated eigen-transformation using the SMT
      representation. In fact, the SMT can be viewed as a generalization of the
      classical fast Fourier transform (FFT) in that it uses "butterflies" to represent
      an orthonormal transform. However, unlike the FFT, the SMT can be used for fast
      eigen-signal analysis of general non-stationary signals.

PMID- 20813642
TI  - Balanced multifilter banks for multiple description coding.
AB  - The parametrization for one kind of multifilter banks generating balanced
      multiwavelets is presented in this paper, in which two lowpass filters are
      flipping filters, and two highpass filters have linear phase. Based on these
      parametric expressions, some balanced multiwavelets and analysis-ready
      multiwavelets are constructed, which are symmetric, or antisymmetric. Moreover,
      on the basis of balanced multiwavelet transform, a new method of multiple
      description coding is given, and experiments show that this method works well.
      Compared with the traditional multiple description coding method, this method has
      low redundancy.

PMID- 20813643
TI  - Random N-finder (N-FINDR) endmember extraction algorithms for hyperspectral
      imagery.
AB  - N-finder algorithm (N-FINDR) has been widely used in endmember extraction. When
      it comes to implementation several issues need to be addressed. One is
      determination of endmembers, p required for N-FINDR to generate. Another is its
      computational complexity resulting from an exhaustive search. A third one is its
      requirement of dimensionality reduction. A fourth and probably the most critical
      issue is its use of random initial endmembers which results in inconsistent final
      endmember selection and results are not reproducible. This paper re-invents the
      wheel by re-designing the N-FINDR in such a way that all the above-mentioned
      issues can be resolved while making the last issue an advantage. The idea is to
      implement the N-FINDR as a random algorithm, called random N-FINDR (RN-FINDR) so
      that a single run using one set of random initial endmembers is considered as one
      realization. If there is an endmember present in the data, it should appear in
      any realization regardless of what random set of initial endmembers is used. In
      this case, the N-FINDR is terminated when the intersection of all realizations
      produced by two consecutive runs of RN-FINDR remains the same in which case the p
      is then automatically determined by the intersection set without appealing for
      any criterion. In order to substantiate the proposed RN-FINDR custom-designed
      synthetic image experiments with complete knowledge are conducted for validation
      and real image experiments are also performed to demonstrate its utility in
      applications.

PMID- 20813644
TI  - Variational region-based segmentation using multiple texture statistics.
AB  - This paper investigates variational region-level criterion for supervised and
      unsupervised texture-based image segmentation. The focus is given to the
      demonstration of the effectiveness and robustness of this region-based
      formulation compared to most common variational approaches. The main
      contributions of this global criterion are twofold. First, the proposed methods
      circumvent a major problem related to classical texture based segmentation
      approaches. Existing methods, even if they use different and various texture
      features, are mainly stated as the optimization of a criterion evaluating
      punctual pixel likelihoods or similarity measure computed within a local
      neighborhood. These approaches require sufficient dissimilarity between the
      considered texture features. An additional limitation is the choice of the
      neighborhood size and shape. These two parameters and especially the neighborhood
      size significantly influence the classification performances: the neighborhood
      must be large enough to capture texture structures and small enough to guarantee
      segmentation accuracy. These parameters are often set experimentally. These
      limitations are mitigated with the proposed variational methods stated at the
      region-level. It resorts to an energy criterion defined on image where regions
      are characterized by nonparametric distributions of their responses to a set of
      filters. In the supervised case, the segmentation algorithm consists in the
      minimization of a similarity measure between region-level statistics and texture
      prototypes and a boundary based functional that imposes smoothness and regularity
      on region boundaries. In the unsupervised case, the data-driven term involves the
      maximization of the dissimilarity between regions. The proposed similarity
      measure is generic and permits optimally fusing various types of texture
      features. It is defined as a weighted sum of Kullback-Leibler divergences between
      feature distributions. The optimization of the proposed variational criteria is
      carried out using a level-set formulation. The effectiveness and the robustness
      of this formulation at region-level, compared to classical active contour
      methods, are evaluated for various Brodatz and natural images.

PMID- 20813645
TI  - A hybrid approach to detect and localize texts in natural scene images.
AB  - Text detection and localization in natural scene images is important for content
      based image analysis. This problem is challenging due to the complex background,
      the non-uniform illumination, the variations of text font, size and line
      orientation. In this paper, we present a hybrid approach to robustly detect and
      localize texts in natural scene images. A text region detector is designed to
      estimate the text existing confidence and scale information in image pyramid,
      which help segment candidate text components by local binarization. To
      efficiently filter out the non-text components, a conditional random field (CRF)
      model considering unary component properties and binary contextual component
      relationships with supervised parameter learning is proposed. Finally, text
      components are grouped into text lines/words with a learning-based energy
      minimization method. Since all the three stages are learning-based, there are
      very few parameters requiring manual tuning. Experimental results evaluated on
      the ICDAR 2005 competition dataset show that our approach yields higher precision
      and recall performance compared with state-of-the-art methods. We also evaluated
      our approach on a multilingual image dataset with promising results.

PMID- 20813646
TI  - Adaptive output feedback NN control of a class of discrete-time MIMO nonlinear
      systems with unknown control directions.
AB  - In this paper, adaptive neural network (NN) control is investigated for a class
      of block triangular multiinput-multioutput nonlinear discrete-time systems with
      each subsystem in pure-feedback form with unknown control directions. These
      systems are of couplings in every equation of each subsystem, and different
      subsystems may have different orders. To avoid the noncausal problem in the
      control design, the system is transformed into a predictor form by rigorous
      derivation. By exploring the properties of the block triangular form, implicit
      controls are developed for each subsystem such that the couplings of inputs and
      states among subsystems have been completely decoupled. The radial basis function
      NN is employed to approximate the unknown control. Each subsystem achieves a
      semiglobal uniformly ultimately bounded stability with the proposed control, and
      simulation results are presented to demonstrate its efficiency.

PMID- 20813647
TI  - Real-time visualized freehand 3D ultrasound reconstruction based on GPU.
AB  - Visualized freehand 3-D ultrasound reconstruction offers to image incremental
      reconstruction during acquisition and guide users to scan interactively for high
      quality volumes. We originally used the graphics processing unit (GPU) to develop
      a visualized reconstruction algorithm that achieves real-time level. Each newly
      acquired image was transferred to the memory of the GPU and inserted into the
      reconstruction volume on the GPU. The partially reconstructed volume was then
      rendered using GPU-based incremental ray casting. After visualized
      reconstruction, hole-filling was performed on the GPU to fill remaining empty
      voxels in the reconstruction volume. We examine the real-time nature of the
      algorithm using in vitro and in vivo datasets. The algorithm can image
      incremental reconstruction at speed of 26-58 frames/s and complete 3-D imaging in
      the acquisition time for the conventional freehand 3-D ultrasound.

PMID- 20813648
TI  - Complementary gene signature integration in multiplatform microarray experiments.
AB  - The concept of gene signature overlap has been addressed previously in a number
      of research papers. A common conclusion is the absence of significant overlap. In
      this paper, we verify the aforementioned fact, but we also assess the issue of
      similarities not on the gene level, but on the biology level hidden underneath a
      given signature. We proceed by taking into account the biological knowledge that
      exists among different signatures, and use it as a means of integrating them and
      refining their statistical significance on the datasets. In this form, by
      integrating biological knowledge with information stemming from data
      distributions, we derive a unified signature that is significantly improved over
      its predecessors in terms of performance and robustness. Our motive behind this
      approach is to assess the problem of evaluating different signatures not in a
      competitive but rather in a complementary manner, where one is treated as a pool
      of knowledge contributing to a global and unified solution.

PMID- 20813649
TI  - GPGPU-aided ensemble empirical-mode decomposition for EEG analysis during
      anesthesia.
AB  - Ensemble empirical-mode decomposition (EEMD) is a novel adaptive time-frequency
      analysis method, which is particularly suitable for extracting useful information
      from noisy nonlinear or nonstationary data. Unfortunately, since the EEMD is
      highly compute-intensive, the method does not apply in real-time applications on
      top of commercial-off-the-shelf computers. Aiming at this problem, a parallelized
      EEMD method has been developed using general-purpose computing on the graphics
      processing unit (GPGPU), namely, G-EEMD. A spectral entropy facilitated by G-EEMD
      was, therefore, proposed to analyze the EEG data for estimating the depth of
      anesthesia (DoA) in a real-time manner. In terms of EEG data analysis, G-EEMD has
      dramatically improved the run-time performance by more than 140 times compared to
      the original serial EEMD implementation. G-EEMD also performs far better than
      another parallelized implementation of EEMD bases on conventional CPU-based
      distributed computing technology despite the latter utilizes 16 high-end
      computing nodes for the same computing task. Furthermore, the results obtained
      from a pharmacokinetics/pharmacodynamic (PK/PD) model analysis indicate that the
      EEMD method is slightly more effective than its precedent alternative method
      (EMD) in estimating DoA, the coefficient of determination R(2) by EEMD is
      significantly higher than that by EMD (p < 0.05, paired t-test) and the
      prediction probability P(k) by EEMD is also slighter higher than that by EMD (p <
      0.2, paired t-test).

PMID- 20813650
TI  - Effect of nerve cuff electrode geometry on onset response firing in high
      frequency nerve conduction block.
AB  - The delivery of high-frequency alternating currents has been shown to produce a
      focal and reversible conduction block in whole nerve and is a potential
      therapeutic option for various diseases and disorders involving pathological or
      undesired neurological activity. However, delivery of high-frequency alternating
      current to a nerve produces a finite burst of neuronal firing, called the onset
      response, before the nerve is blocked. Reduction or elimination of the onset
      response is very important to moving this type of nerve block into clinical
      applications since the onset response is likely to result in undesired muscle
      contraction and pain. This paper describes a study of the effect of nerve cuff
      electrode geometry (specifically, bipolar contact separation distance), and
      waveform amplitude on the magnitude and duration of the onset response. Electrode
      geometry and waveform amplitude were both found to affect these measures. The
      magnitude and duration of the onset response showed a monotonic relationship with
      bipolar separation distance and amplitude. The duration of the onset response
      varied by as much as 820% on average for combinations of different electrode
      geometries and waveform amplitudes. Bipolar electrodes with a contact separation
      distance of 0.5 mm resulted in the briefest onset response on average.
      Furthermore, the data presented in this study provide some insight into a
      biophysical explanation for the onset response. These data suggest that the onset
      response consists of two different phases: one phase which is responsive to
      experimental variables such as electrode geometry and waveform amplitude, and one
      which is not and appears to be inherent to the transition to the blocked state.
      This study has implications for nerve block electrode and stimulation parameter
      selection for clinical therapy systems and basic neurophysiology studies.

PMID- 20813651
TI  - Wireless transmission of neural signals using entropy and mutual information
      compression.
AB  - Two of the most critical tasks when designing a portable wireless neural
      recording system are to limit power consumption and to efficiently use the
      limited bandwidth. It is known that for most wireless devices the majority of
      power is consumed by the wireless transmitter and it often represents the
      bottleneck of the overall design. This paper compares two compression techniques
      that take advantage of the sparseness of the neural spikes in neural recordings
      using an information theoretic formalism to enhance the well-established vector
      quantization (VQ) algorithm. The two discriminative VQ algorithms are applied to
      neuronal recordings proving their ability to accurately reconstruct action
      potential (AP) regions of the neuronal signal while compressing background
      activity without using thresholds. The two operational modes presented offer
      distinct characteristics to lossy compression. The first approach requires no
      preprocessing or prior knowledge of the signal while the second requires a
      training set of spikes to obtain AP templates. The compression algorithms are
      implemented on an on-board digital signal processor (DSP) and results show that
      power consumption is decreased while the bandwidth is more efficiently utilized.
      The compression algorithms have been tested in real time on a hardware platform
      (PICO DSP ) enhanced with the DSP which runs the algorithm before sending the
      compressed data to a wireless transmitter. The compression ratios obtained range
      from 70:1 and 40:1 depending on the signal to noise ratio (SNR) of the input
      signal. The spike sorting accuracy in the reconstructed data is 95% compatible to
      the original neural data.

PMID- 20813652
TI  - Effects of biphasic current pulse frequency, amplitude, duration, and interphase
      gap on eye movement responses to prosthetic electrical stimulation of the
      vestibular nerve.
AB  - An implantable prosthesis that stimulates vestibular nerve branches to restore
      sensation of head rotation and vision-stabilizing reflexes could benefit
      individuals disabled by bilateral loss of vestibular (inner ear balance)
      function. We developed a prosthesis that partly restores normal function in
      animals by delivering pulse frequency modulated (PFM) biphasic current pulses via
      electrodes implanted in semicircular canals. Because the optimal stimulus
      encoding strategy is not yet known, we investigated effects of varying biphasic
      current pulse frequency, amplitude, duration, and interphase gap on vestibulo
      ocular reflex (VOR) eye movements in chinchillas. Increasing pulse frequency
      increased response amplitude while maintaining a relatively constant axis of
      rotation. Increasing pulse amplitude (range 0- 325 MUA) also increased response
      amplitude but spuriously shifted eye movement axis, probably due to current
      spread beyond the target nerve. Shorter pulse durations (range 28- 340 MUs)
      required less charge to elicit a given response amplitude and caused less axis
      shift than longer durations. Varying interphase gap (range 25- 175 MUs) had no
      significant effect. While specific values reported herein depend on microanatomy
      and electrode location in each case, we conclude that PFM with short duration
      biphasic pulses should form the foundation for further optimization of stimulus
      encoding strategies for vestibular prostheses intended to restore sensation of
      head rotation.

PMID- 20813653
TI  - Muscle plasticity in rat following spinal transection and chronic intraspinal
      microstimulation.
AB  - Intraspinal microstimulation (ISMS) employs electrical stimulation of the ventral
      grey matter to reactivate paralyzed skeletal muscle. This work evaluated the
      transformations in the quadriceps muscle that occurred following complete
      transection and chronic stimulation with ISMS or a standard nerve cuff (NCS).
      Stimulation was applied for 30 days, 4 h/day. Both methods induced significant
      increases in time-to-peak tension (ISMS 35%, NCS 25%) and half rise-time (ISMS
      39%, NCS 25%) compared to intact controls (IC). Corresponding increases in type
      IIA myosin heavy chain (MHC) and decreases in type-IID MHC were noted compared to
      IC. These results were unexpected because ISMS recruits motor units in a near
      normal physiological order while NCS recruits motor units in a reversed order.
      Spinal cord transection and 30 days of stimulation did not alter either
      recruitment profile. The slope of the force recruitment curves obtained through
      ISMS following transection and 30 days of stimulation was similar to that
      obtained in intact animals, and 3.4-fold shallower than that obtained through
      NCS. The transformations observed in the current work are best explained by the
      near maximal level of motor unit recruitment, the total daily time of activity
      and the tonic nature of the stimulation paradigm.

PMID- 20813654
TI  - No association between arsenic exposure from drinking water and diabetes
      mellitus: a cross-sectional study in Bangladesh.
AB  - BACKGROUND: The long-term effects of arsenic exposure from drinking water at
      levels < 300 microg/L and the risk of diabetes mellitus remains a controversial
      topic. METHOD: We conducted a population-based cross-sectional study using
      baseline data from 11,319 participants in the Health Effects of Arsenic
      Longitudinal Study in Araihazar, Bangladesh, to evaluate the associations of well
      water arsenic and total urinary arsenic concentration and the prevalence of
      diabetes mellitus and glucosuria. We also assessed the concentrations of well
      water arsenic, total urinary arsenic, and urinary arsenic metabolites in relation
      to blood glycosylated hemoglobin (HbA1c) levels in subsets of the study
      population. RESULTS: More than 90% of the cohort members were exposed to drinking
      water with arsenic concentration < 300 microg/L. We found no association between
      arsenic exposure and the prevalence of diabetes. The adjusted odds ratios for
      diabetes were 1.00 (referent), 1.35 [95% confidence interval (CI), 0.90-2.02],
      1.24 (0.82-1.87), 0.96 (0.62-1.49), and 1.11 (0.73-1.69) in relation to quintiles
      of time-weighted water arsenic concentrations of 0.1-8, 8-41, 41-91, 92-176, and
      > or = 177 microg/L, respectively, and 1.00 (referent), 1.29 (0.87-1.91), 1.05
      (0.69-1.59), 0.94 (0.61-1.44), and 0.93 (0.59-1.45) in relation to quintiles of
      urinary arsenic concentrations of 1-36, 37-66, 67-114, 115-204, and > or = 205
      microg/L, respectively. We observed no association between arsenic exposure and
      prevalence of glucosuria and no evidence of an association between well water
      arsenic, total urinary arsenic, or the composition of urinary arsenic metabolites
      and HbA1c level. CONCLUSIONS: Our findings do not support an association of
      arsenic exposure from drinking water and a significantly increased risk of
      diabetes mellitus in the range of levels observed. Further prospective studies
      would be valuable in confirming the findings.

PMID- 20813655
TI  - Case report: the University of Michigan dioxin exposure study: a follow-up
      investigation of a case with high serum concentration of 2,3,4,7,8
      pentachlorodibenzofuran.
AB  - CONTEXT: Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and
      dioxin-like polychlorinated biphenyls that have toxic equivalency factors (TEFs)
      were measured in serum of 946 subjects in five Michigan counties. The study was
      motivated by concerns about human exposure to dioxin-contaminated sediments in
      the Tittabawassee River (TR). Most of the toxic equivalency in TR sediments is
      from two furan congeners, 2,3,7,8-tetrachlorodibenzofuran and 2,3,4,7,8
      pentachlorodibenzofuran (2,3,4,7,8-pentaCDF). CASE PRESENTATION: The individual
      with the highest adjusted (for age, age squared, and body mass index) serum level
      of 2,3,4,7,8-pentaCDF in the study (42.5 ppt) reported a unique history of
      raising cattle and vegetables in the floodplain of the TR. Interviews and serum
      samples were obtained from the index case and 15 other people who ate beef and
      vegetables raised by the index case. 2,3,4,7,8-pentaCDF in beef lipid was
      estimated to have been more than three orders of magnitude greater than
      background (1,780 vs. 1.1 ppt). The mean, median, and 95th percentile for serum
      2,3,4,7,8-pentaCDF in the study control population were 6.0, 5.4, and 13.0 ppt,
      respectively, and were 9.9, 8.4, and 20.5 ppt among beef and vegetable consumers,
      respectively. Back extrapolation for the index case suggests that his increase in
      serum concentration of 2,3,4,7,8-pentaCDF above background may have been as high
      as 146 ppt. DISCUSSION: Consumption of beef and/or vegetables raised on dioxin
      contaminated soil may be an important completed pathway of exposure. RELEVANCE TO
      PUBLIC HEALTH PRACTICE: Animals and crops should not be raised for human
      consumption in areas contaminated with dioxins.

PMID- 20813656
TI  - [Rare tumours: a new heading in Bulletin du cancer].
AB  - Rare cancers are defined by an incidence less than 5/100,000, which means in
      France less than 3,000 new cases a year. They are difficult to diagnose, their
      physiopathology has led to new knowledge in cancer medicine. There is no large
      experience for their management, and they are not generally the subject of
      randomized trials to establish treatment strategy. Therefore they are often
      managed by suboptimal cares. Even individually rare cancers do not concern large
      populations, the number of patients suffering of rare cancer is important. This
      is the reason why the "Bulletin du cancer" will open a new section on rare
      cancers. This article aims to draw the context of such a decision, based on an
      effort to allow these patients to receive optimal management.

PMID- 20813657
TI  - [Epidemiology and management of rare paediatric tumours within the framework of
      the French Society for Children Cancer].
AB  - Less than 1% of cancer occurs in children. With the progress made by national and
      international cooperative groups 75% of them are actually cured. However some
      entities have an incidence so weak that we can't actually establish standardized
      therapeutics guidelines. To improve our knowledge on these rare tumours a
      national organisation become necessary as well as an international collaboration.
      A French rare tumour committee was created within the French Society for Children
      Cancer (SFCE). Others European countries have such organisation. The objectives
      of these tasks groups are to enhance our knowledge of the real incidence of these
      rare tumours, their evolution, and to propose therapeutic recommendations for
      each of them. This article focuses on the specific French organization for rare
      tumours treatment. It also describes the draft for the creation of a new data
      base for prospective registry of clinical, therapeutics and follow up data. To
      provide a better understanding of these pathologies, the "Bulletin du Cancer's"
      editorial board decided to regularly publish an update on a rare paediatric
      tumour in a specific section.

PMID- 20813658
TI  - [Child pleuropulmonary blastoma].
AB  - Pleuropulmonary blastoma is an extremely rare and aggressive thoracic tumour seen
      exclusively in children. The initial symptoms are respiratory and non specific
      and the chest X-ray done in that context reveals a thoracic mass. The chest CT
      scan then leads to the diagnosis of a cystic, mixt or solid mass. The diagnosis
      will be affirmed on anatomopathology of the tumour or biopsy. There are three
      different histological types: type I, cystic, type II, cystic and solid and type
      III, solid exclusively. Type I is less aggressive and its treatment is
      essentially surgical. Types II and III are highly aggressive and require surgery
      associated to polychemotherapy. In all cases, surgery is essential and should be
      the most complete possible. Extension and follow-up exams will include bone scan
      and brain imagery searching for metastasis as well as abdominal ultrasound
      searching associated renal lesions because 30% of pleuropulmonary blastoma are
      part of a familial predisposition syndrome.

PMID- 20813659
TI  - [Effects of patient age, number and quality of embryo transferred on the outcome
      of in vitro fertilization-embryo transfer].
AB  - OBJECTIVE: To study the effect of patient age, the number and quality of embryo
      transferred on pregnancy outcome of in vitro fertilization-embryo transfer (IVF
      ETs). METHODS: A retrospective study was performed in infertile women who
      underwent a total of 1800 cycles of IVF-ET and intracytoplasmic sperm injection
      (ICSI). The patients were divided into three age groups, namely<30 years group,
      30-35 years group, and>or=35 years group. The clinical pregnancy rate and the
      multiple pregnancy rate were compared when 1, 2 or 3 embryos and 0, 1, 2 or 3
      good-quality embryos were transferred. RESULTS: In patients<30 years, no
      significant differences was found in the clinical pregnancy rate between 1, 2 and
      3 embryos transfer groups; 2 and 3 good-quality embryos transfer resulted in
      similar pregnancy rate, which was significantly higher than that resulted from 0
      and 1 good-quality embryo transfer. Multiple pregnancy was not found in 1 embryo
      transfer group. In patients aged 30-35 years, the pregnancy rate showed no
      significant differences not only between 1 and 2 embryos transfer groups, but
      also between 2 and 3 good-quality embryos transfer groups; multiple embryo
      transfer led to significantly increased multiple pregnancy rate. In patients
      aged>or=35 years, the transfer of 1, 2 and 3 embryos resulted in similar
      pregnancy rate; transfer of 3 good-quality embryos had obviously higher pregnancy
      rate than 0, 1 and 2 good-quality embryos transfer groups. Increased numbers of
      embryos and good-quality embryos transferred were both associated with increased
      multiple pregnancy rate. CONCLUSION: One good-quality embryo transfer in
      patients<30 years and 2 good-quality embryos transfer in patients>or=30 years can
      obtain ideal pregnancy rate and reduce the incidence of multiple pregnancy. For
      patients aged>or=35 years, transfer of only good-quality embryo is recommended.

PMID- 20813660
TI  - [Protein kinase D3 is involved in negative regulation of MMP-7 in prostate cancer
      cells].
AB  - OBJECTIVE: To explore the role of protein kinase D3 (PKD3) in the regulation of
      matrix metalloproteinases 7 (MMP-7) expression in prostate cancer cells. METHODS:
      PC-3 cells were either stimulated with 100 nmol/L PMA to activate PKD3 kinase
      activity, or transiently transfected with PKD3 siRNA, and the relative expression
      level of MMP-7 mRNA were analyzed by real-time PCR using 2(-delta delta Ct)
      method. MMP-7 mRNA levels were also analyzed and quantified in HEK293 cells with
      over-expression of wild-type PKD3, PKD3 knockdown (using PKD3 siRNA), or over
      expression of wild-type PKD3 followed by PKD3 knockdown. RESULTS: MMP-7 mRNA
      expression in PC3 cells was significantly decreased after PMA-induced PKD3 kinase
      activation. In contrast, PKD3 knockdown by siRNA transfection markedly increased
      MMP-7 mRNA level (P<0.01). MMP-7 mRNA level in HEK293 cells was significantly
      decreased by PKD3 over-expression, whereas obviously increased by PKD3 knockdown.
      Down-regulation of MMP-7 mRNA level in HEK293 induced by PKD3 over-expression was
      rescued by PKD3 knockdown. CONCLUSION: PKD3 may contribute to the malignant
      progression of prostate cancer cells through negative regulation of MMP-7
      expression.

PMID- 20813661
TI  - [Analysis and verification of the interaction network of differentially expressed
      genes in invasive bladder cancer].
AB  - OBJECTIVE: To study the data of gene expression microarray by protein interaction
      network analysis, establish an interaction network of differentially expressed
      genes in invasive bladder cancer and verify the central nodes of the network.
      METHODS: A total of 152 differentially expressed genes in invasive bladder cancer
      detected by gene expression microarray were inputted into STRING database online
      for analysis and establishment of the interaction network. The interaction data
      were imported into Cytoscape 2.6.2 software for screening the central nodes of
      the network. KEGG database was exploited for pathway analysis and functional
      study of the central node genes. Real-time RT-PCR was used for verification, and
      the genes with maximal differential expressions were screened for exploring the
      molecular mechanism of carcinogenesis of invasive bladder cancer. RESULTS: The
      protein products of 103 differentially expressed genes in bladder cancer had
      interactions, forming a complicated interaction network. Twenty-six nodes
      involved in several signal pathways were confirmed by Cytoscape as the central
      nodes of the network, among which UBE2C, VEGF, TGFBR2, and CAV1 nodes were
      verified by real-time RT-PCR as the genes with maximal differential expressions
      between the bladder cancer and normal tissues, and the 2(-delta delta Ct) of
      these genes were 9.45, 4.17, 0.13 and 0.18 (GAPHD as the internal control),
      respectively. CONCLUSION: The interaction network of the differentially expressed
      genes, especially the central nodes of this network, can provide clues to the
      carcinogenesis, early diagnosis and molecular targeted therapy of invasive
      bladder cancer.

PMID- 20813662
TI  - [Hepatitis B virus X protein suppresses adriamycin-induced apoptosis of
      hepatocellular carcinoma cells and expression of p53 and PTEN].
AB  - OBJECTIVE: To investigate the effect of hepatitis B virus X protein (HBx) on
      adriamycin-induced apoptosis of hepatocellular carcinoma cells and the
      expressions of p53 and PTEN. METHODS: HepG2, HepG2/GFP, and HepG2/GFP-HBx cells
      were treated with adriamycin (2.5 microg/ml), and the apoptotic cell death was
      determined by observing the morphological changes and flow cytometry. The
      expressions of p53 and PTEN mRNA in the 3 cells were detected by RT-PCR, and the
      expressions of p53 and PTEN protein were analyzed by Western blotting. RESULTS:
      Adriamycin induced significant cell death in HepG2 and HepG2/GFP cells, which
      became rounded, shrunk, and detached after the treatment; but no significant cell
      death occurred in HepG2/GFP-HBx cells. Flow cytometry analysis showed that the
      apoptotic rate was significantly lower in HepG2/GFP-HBx cells (3.94%) than in
      HepG2 (59.03%) and HepG2/GFP cells (61.38%) at 36 h after the treatment
      (P<0.001), while no significant difference was observed between HepG2/GFP-HBx
      (3.94%) and the control cells (2.12%, 2.78%, and 2.55%) (P>0.05). RT-PCR showed
      lowered expression of PTEN mRNA in HepG2/GFP-HBx cells as compared to that in
      HepG2 and HepG2/GFP cells, while no significant difference was noted in p53 mRNA.
      Western blot analysis showed that PTEN protein decreased while p53 protein remain
      unchanged in HepG2/GFP-HBx cells. CONCLUSION: HBx suppresses adriamycin-induced
      apoptosis of HepG2 cells and PTEN expression. The inhibitory effect of HBx on the
      cell apoptosis may be related to the inhibition of p53-PTEN pathway.

PMID- 20813663
TI  - [PKD3 contributes to up-regulation of prostate-specific antigen in prostate
      cancer cells].
AB  - OBJECTIVE: To investigate the role of PKD3 in prostate-specific antigen (PSA)
      expression regulation in androgen-dependent prostate cancer cells and explore the
      mechanism. METHODS: LNCaP cells containing low level of PKD3 were transfected
      with pEGFP-C2 or pEGFP-PKD3 plasmid followed by dihydrotestosterone (DHT)
      treatment, and PSA mRNA level was analyzed by RT-QPCR using 2(-delta delta Ct)
      method. Wild-type or kinase-dead PKD3 plasmids, human androgen receptor plasmid
      pSVAR0, pMMTV-luc of AR luciferase reporter and renilla luciferase reporter pRL
      SV40 were cotransfected into HEK293 cells, and after treatment with DHT for 24 h,
      the cells were harvested and AR transcriptional activity were determined by dual
      luciferase reporter assay. The subcellular localization of endogenous PKD3 and AR
      and their colocalization induced by DHT were observed by confocal microscopy.
      RESULTS: PSA mRNA level triggered by DHT was significantly increased by
      overexpression of pEGFP-PKD3 in LNCaP cells compared with that in pEGFP-C2
      control cells (P<0.001). AR transcription in response to DHT treatment was also
      significantly up-regulated by wild type PKD3 expression (P<0.001), but partially
      down-regulated by kinase-dead PKD3 mutant (P<0.01). Endogenous PKD3 and AR in
      LNCaP cells not only translocated from the cytoplasm to the nucleus, but also
      colocalized with each other after DHT stimulation. CONCLUSION: Elevated AR
      transcriptional activity and enhanced expression of PSA induced by PKD3 in
      response to DHT treatment suggest that PKD3 contributes to the proliferation and
      malignant growth of androgen-dependent prostate cancer cells.

PMID- 20813664
TI  - [GABAergic neurons in the central nucleus of amygdala modulate sodium appetite in
      rats].
AB  - OBJECTIVE: To determine whether the GABA-containing neurons in rat central
      nucleus of amygdala (CeA) can be activated by acute sodium deprivation. METHODS:
      Acute sodium depletion was induced by subcutaneous injection of furosemide in
      rats followed by 24 h of dietary sodium deprivation. The rats underwent 0.3 mol/L
      NaCl/distilled water two bottle choice test, and the activated neurons were
      labeled and identified with GABA/Fos-double labeling immunohistochemistry.
      RESULTS: The rats with acute sodium depletion exhibited significantly more
      numerous c-fos-positive neurons and GABA/Fos double-labeled neurons in the CeA
      than the control group (P<0.01, P<0.05). Consumption of 0.3 mol/L NaCl
      significantly increased the number of c-fos and GABA/Fos double labeled neurons
      compared to the distilled water group (P<0.001, P<0.01). CONCLUSION: GABAergic
      neurons in the CeA may play an inhibitory role in the regulation of sodium intake
      in rats with acute sodium depletion.

PMID- 20813665
TI  - [Effect of NAD+ against radiation injury and its dose-effect relationship].
AB  - OBJECTIVE: To explore the effect of NAD+ against radiation injury and its dose
      effect relationship. METHODS: L02 liver cells cultured in RPMI 1640 medium
      containing 10% fetal calf serum were exposed to X-ray irradiation followed by
      immediate application of NAD+. The cellular viability was analyzed by MTT assay
      and the apoptotic cells were detected by TUNEL methods to observe the damages of
      L02 liver cells induced by X-ray exposure and analyze the dose-effect
      relationship of NAD+. RESULTS: The viability of L02 liver cells was decreased
      with increasing dose of X-ray irradiation. The most obvious growth inhibition of
      L02 cells occurred 24 h after the irradiation. NAD+ significantly increased the
      cell survival rate after irradiation, and this effect was gradually increased
      within the concentration range of 100-1000 microg/ml; at higher concentrations,
      the survival rate of the irradiated L02 cells showed no significant increase.
      CONCLUSION: NAD+ provides partial protection of the liver cells against radiation
      injury, and the effect is positively correlated to NAD+ concentration within a
      certain range.

PMID- 20813666
TI  - [Preparation of As2O3 nanoparticles and its drug release characteristics in
      vitro].
AB  - OBJECTIVE: To prepare arsenic trioxide (As2O3)-loaded biodegradable polylactic-co
      glycolic acid (PLGA) nanoparticles (NPS) and evaluate the glomeration ability,
      appearance, structure, surface and release characteristics of the NPs. METHODS:
      With PLGA as the carrier material, As2O3 NPs (As2O3-NPS) were prepared with the
      method of matrix and ultrasound emulsification. According to the criteria of the
      diameter of the NPs, drug loading (DL) and embedding ratio (ER), the process of
      NP preparation was optimized by scanning electron microscopy (SEM), ultraviolet
      spectroscopy (UV), and XPS. RESULTS: The As2O3-NPS prepared were uniformly
      spherical with an average diameter of 210-/+23 nm, DL of 29.6% and ER of 82.1%.
      The drug release assay in vitro showed a sustained drug-release capacity of the
      preparation. CONCLUSION: As2O3-NPS may serve as a carrier of As2O3 to change the
      pharmacokinetics of As2O3 in vivo, allow slow drug release, and prolong the drug
      circulation time after intravenous injection, thereby producing better antitumor
      effects.

PMID- 20813667
TI  - [Construction of a eukaryotic expression vector expressing human IFN-gamma and
      its inhibitory effect on HBV replication in vitro].
AB  - OBJECTIVE: To observe the inhibitory effect of a eukaryotic expression vector
      expressing human IFN-gamma (pcDNA3.1- IFN-gamma) on HBV replication in hepG2.2.15
      cells. METHODS: The eukaryotic expression vector expressing human IFN-gamma was
      constructed using PCR and gene recombination technique. hepG2.2.15 cells were
      transfected with pcDNA3.1-IFN-gamma and the culture supernatant was collected to
      determine the expression of IFN-gamma protein by ELISA. The HBV DNA copies and
      the concentration of HBeAg and HBsAg were measured by fluorescence real-time PCR
      and ELISA kit, respectively. RESULTS: Compared with that of negative control and
      blank 2.2.15 cells, the concentration of HBeAg in the supernatant of 2.2.15 cells
      transfected with pcDNA3.1- IFN-gamma were decreased by 49%, and HBsAg
      concentration was lowered by 35% and 33%, respectively. A significant decrease of
      HBV DNA copies was observed in pcDNA3.1- IFN-gamma-transfected cells in
      comparison with the two control cells. No significant differences were noted in
      all the results between the two control groups. CONCLUSION: We have successfully
      constructed the eukaryotic expression vector expressing human IFN-gamma, which
      provides a basis for anti-HBV gene therapy using human IFN-gamma.

PMID- 20813668
TI  - [Establishment of a bladder cancer cell line with toll-like receptor 2 gene
      knockdown and identification of its biological characteristics].
AB  - OBJECTIVE: To establish a murine bladder cancer cell line with stable silencing
      of toll-like receptor 2 (TLR2) expression. METHODS: Three different recombinant
      plasmids pcDNA 6.2-GW/EmGFPmiR-TLR2 were constructed and transfected into T739
      cells via lipofectamine. The recombinant plasmid with the strongest interference
      effect was selected by RT-PCR and transfected into T739 cells. The Blasticidin
      resistant cell clones were screened to obtain bladder cancer cell lines with TLR2
      gene knockdown, and the biological characteristics of the stable cell lines were
      observed. RESULTS: Sequencing showed that the target DNA fragment was correctly
      inserted into the vector. The recombinant plasmid with the strongest silencing
      effect (pcDNA 6.2-GW/EmGFPmiR- TLR2.949) was screened, and transfection of this
      plasmid in T739 cells resulted in a cell line with stable TLR2 gene silencing
      (T739-TLR2delta), in which the expression of TLR2 mRNA and receptor were
      downregulated by over 95% and 90%, respectively. Compared with the negative
      control cells, T739-TLR2delta cell line exhibited significant different cell
      proliferation index with extended cell population doubling time. CONCLUSION: The
      recombinant plasmid pcDNATM6.2-GW/EmGFPmiR-TLR2 can effectively suppress the
      expression of TLR2 gene, and the established cell line with stable TLR-2 gene
      knockdown allows further functional study the TLR2 gene in T739 cells.

PMID- 20813669
TI  - [Prevalence of internet addiction and the related factors in middle school
      students in Guangzhou].
AB  - OBJECTIVE: To study the status of and the factors contributing to Internet
      addiction among middle school students in Guangzhou. METHODS: Cluster sampling
      method was used to recruit an urban middle school, a rural junior middle school
      and a rural senior high school to conduct the survey with the stressful life
      event questionnaire, the trait-oriented coping styles questionnaire and the
      Internet Addiction Test. RESULTS: The majority of respondents were classified as
      normal users of the Internet (n=1392, 89.2%), with 158 (10.2%) moderately and 10
      (0.6%) severely addicted to the Internet. Fifty-eight students had never used the
      Internet. There were significant differences in gender, the father's education,
      the 4 dimensions of the stressful life event questionnaire and the coping styles
      between students with and without Internet addiction. Binary logistic analysis
      showed that the factors contributing to Internet addiction included passive
      coping styles, male gender and stressful life event experienced in family and
      interpersonal communication. CONCLUSIONS: The incidence of Internet addiction is
      high among middle school students in Guangzhou. Male students with stressful life
      events in family and interpersonal communication, poor education on the part of
      the father, and frequent use of negative coping styles are more likely to develop
      Internet addiction.

PMID- 20813670
TI  - [Study of three-dimensional speech chart by time-frequency analysis in Chinese
      Mandarin Monosyllabic word phonemes].
AB  - OBJECTIVE: To investigate the physical characteristic of Chinese Mandarin
      Monosyllabic word phonemes by the time-frequency analysis. METHODS: Manufactured
      and study the three-dimensional speech chart which was on the basic of
      information of the time-frequency analysis in 40 monosyllabic words with the
      SigmaPlot 9.0 and Matlab 7.0 software. RESULTS: The mean value of basic frequency
      in 40 monosyllabic words was between 220 to 320 Hz area, and the mean value of
      four groups has significant difference by t-test. It is indicated by time
      frequency analysis that the characteristics vary according to the tone of
      monosyllabic words. With the change of time, the various frequencies and its
      intensity of tone first remain basically unchanged, the curve is horizontal type;
      the different frequencies of tone second gradually tend to high-frequency
      direction, the graph is upward-type, additionally, the intensity of some tone
      drops little; the divers frequencies of tone third firstly deflect to low
      frequency areas, then increasingly deviate to high-frequency direction of bias
      after maintaining a period of time, the figure is v-type, intensity changes are
      concave-shaped; The various frequencies of tone fourth deviate from high
      frequency to low-frequency areas, and its intensity drops sharply, the graph is
      decreased type. CONCLUSION: Through time-frequency analysis and three-dimensional
      speech chart observation, we consider that the physical characteristic of Chinese
      Mandarin Monosyllabic word phonemes mainly reflects the frequencies and intensity
      change with time.

PMID- 20813671
TI  - [Effects of radiosensitivity and X-ray dose on miR-7 expression in nasopharyngeal
      carcinoma].
AB  - OBJECTIVE: To investigate the effects of radiosensitivity and X-ray dose on the
      expression of miR-7 in nasopharyngeal carcinoma (NPC) cells. METHODS: Low
      radiosensitive NPC cells CNE-1 and high radiosensitive NPC cells CNE-2 were
      exposed to 0, 2 and 8 Gy X-ray. The total RNAs of the cell lines were extracted
      10 h after radiation for reverse transcription of miR-7 and 18S rRNA by stem-loop
      primer and random hexamers, respectively. The non-irradiated CNE-1 cells served
      as the control sample and the relative quantity of the expression level was
      calculated after real-time PCR using SyBR green. RESULTS: miR-7 expression
      differed significantly between CNE-1 and CNE-2 cells (4.49-/+3.62 vs 1.29-/+1.10,
      F=135.483, P<0.001). The radiation dose also significantly affected the
      expression of miR-7 in NPC cells (F=39.565, P<0.001). CNE-1 cells with a 2 Gy
      exposure had the highest expression level of miR-7, while the non-irradiated CNE
      1 cells had the lowest expression. CNE-2 cells exposed to 2 Gy X-ray had the
      lowest expression level of miR-7 and the non-irradiated CNE-2 cells had the
      highest. CONCLUSION: Radiosensitivity and radiation dose of X-ray have
      significant effect on the expression of miR-7 in NPC cells, indicating that miR-7
      plays an important role in radioresistance of NPC cells to X-ray, and suppressed
      miR-7 expression may elevate the radiosensitivity of NPC cells.

PMID- 20813672
TI  - [Group II metabotropic glutamate receptors is involved in the modulation of
      respiratory rhythmical discharge activity in neonatal rat medullary brain
      slices].
AB  - OBJECTIVE: To explore the role of group II metabotropic glutamate receptors in
      the modulation of basic respiratory rhythm. METHODS: Neonatal (0-3 days) SD rats
      of either sex were used. The medulla oblongata brain slice containing the medial
      region of the nucleus retrofacialis (mNRF) and the hypoglossal nerve rootlets was
      prepared, and the surgical procedure was performed in the modified Kreb's
      solution (MKS) with continuous carbogen (95% O2 and 5% CO2) within 3 min. The
      brain slices were quickly transferred to a recording chamber and continuously
      perfused with oxygen-saturated MKS at a rate of 4-6 ml/min at 27-29 degrees
      celsius. Eighteen medulla oblongata slices were divided into 3 groups and treated
      for 10 min with group II metabotropic glutamate receptor-specific agonist 2R,4R-4
      aminopyrrolidine-2,4-dicarboxylate (APDC) (at concentrations of 10, 20, 50
      micromol/L), group II metabotropic glutamate receptor antagonist (2S)-alpha
      ethylglutamic acid (EGLU) (300 micromol/L), or APDC (50 micromol/L)+EGLU (300
      micromol/L) after a 10 min APDC (50 micromol/L) application. Respiratory
      rhythmical discharge activity (RRDA) of the rootlets of the hypoglossal nerve was
      recorded by suction electrodes. RESULTS: APDC produced a dose-dependent
      inhibitory effect on the RRDA, prolonging the respiratory cycle and expiratory
      time and decreasing the integral amplitude and inspiratory time. EGLU induced a
      significant decrease in the respiratory cycle and expiratory time. The effect of
      APDC on the respiratory rhythm was partially reversed by the application of
      APDC+EGLU. CONCLUSION: Group II metabotropic glutamate receptors are probably
      involved in the modulation of the RRDA in isolated neonatal rat brainstem slice.

PMID- 20813673
TI  - [Effect of anti-EGFR monoclonal antibody on chemosensitivity of human colon
      cancer cells and the mechanism].
AB  - OBJECTIVE: To investigate the effect of anti-EGFR monoclonal antibody on the
      chemosensitivity of human colon cancer cells and explore the possible molecular
      mechanism. METHODS: The inhibitory effect of irinotecan (CPT-11), oxaliplatin (L
      OHP) and fluorouracil (5-Fu), used alone or in combination with anti-EGFR
      monoclonal antibody, on the proliferation of LoVo cells in vitro was assessed by
      MTT assay. The expressions of PI3K and Akt protein in the treated cells were
      examined by Western blotting, and their mRNA expressions were detected by RT-PCR.
      RESULTS: Both h-R3 and C-225 treatments significantly increased the
      chemosensitivity of LoVo cells to irinotecan and oxaliplatin. 5-Fu and h-R3
      coadministered showed a synergistic effect on the cells, but 5-Fu and C-225 had
      an antagonistic action. Treatment with C-225 or h-R3 resulted in lowered
      expressions of PI3K and Akt in LoVo cells. CONCLUSION: Anti-EGFR monoclonal
      antibody can increase the chemosensitivity of human colon cancer cells to most
      chemotherapeutic drugs, and such effect might be attributed to the blocking of
      PI3K/Akt signaling pathway by these antibodies.

PMID- 20813674
TI  - [Application of lumbar-pelvic fixation in lumbosacral reconstruction after
      resection of sacral tumors].
AB  - OBJECTIVE: To evaluate the short-term clinical results of a new approach of
      lumbar-pelvic fixation for lumbosacral reconstruction after resection of sacral
      tumors. METHODS: Fifteen patients with sacral tumors underwent lumbar-pelvic
      fixation using TSRH-3D, CDH-M8 or ISOLA with iliac screws. The lumbosacral
      stability was evaluated according to the X-ray result to assess the feasibility
      and therapeutic effect of this approach. RESULTS: X-ray showed that high
      lumbosacral stability was achieved in all the 15 cases after the operation, and
      satisfactory therapeutic effect was obtained. CONCLUSION: Lumbar-pelvic fixation
      with iliac screw is feasible for lumbosacral reconstruction after resection of
      the sacral tumors, which provides strong internal fixation and produce good
      clinical outcomes.

PMID- 20813675
TI  - [Effects of morphine and pethidine on the expression of P-glycoprotein in mouse
      brain microvascular endothelial cells].
AB  - OBJECTIVE: To observe the effects of morphine and pethidine on P-glycoprotein (P
      gp) expression in mouse brain microvascular endothelial cells and investigate the
      role of nuclear factor-kappaB (NF-kappaB) signaling pathway in morphine-induced
      up-expression of P-gp. METHODS: The mouse brain microvascular endothelial cell
      line (b.END3) was subjected to pre-incubation with NF-kappaB inhibitor PDTC (5
      micromol/L) for 1 h followed by stimulation with morphine (1 microg/ml) or
      pethidine (1 microg/ml) for 24 h. The bEnd.3 cells were then collected for
      Western blotting for P-gp expression. RESULTS: A 24-h morphine stimulation
      induced an up-expression of P-gp in bEnd.3 cells by almost 200%. Pethidine in
      similar conditions did not affect P-gp expression in the cells. PDTC, the
      specific inhibitor of NF-kappaB, inhibited morphine-induced up-expression of P-gp
      in the cells. CONCLUSION: Morphine can induce up-expression of endogenous P-gp in
      mouse brain microvascular endothelial cells. NF-kappaB signaling pathway is
      involved in the morphine-induced up-expression of P-gp.

PMID- 20813676
TI  - [High-performance liquid chromatography for determining celecoxib concentration
      in hamster tongue tissue after oral local application].
AB  - OBJECTIVE: To establish a high-performance liquid chromatography (HPLC)-based
      method for determining celecoxib concentration in the tongue tissue of hamsters.
      METHODS: Celecoxib mixed with the matrix (final concentration of 6%) was smeared
      on the surface of the tongue mucosa of hamsters, and the concentration and
      absorption rate of celecoxib in the tongue tissue were determined by HPLC at 5,
      10, 15, 30, 60, 90, 120 min after the application. RESULTS: In this system, the
      retention time of celecoxib was 4.4 min. Celecoxib concentration showed a good
      linear range within 25-800 microg/L (R2=0.9991, n=6), with the detection limit
      for celecoxib of 10 g/L (S/N=3). The extraction recoveries and method recoveries
      for celecoxib were 83.75%-90.01% and 91.98%-99.07%, respectively. The inter-day
      RSDs were 2.15%, 3.16% and 3.67%, and intra-day RSDs were 3.40%, 4.56% and 4.42%,
      respectively. The concentration of celecoxib in hamster tongue tissue within the
      first 120 min ranged from 0.685-/+0.019 microg/g to 3.168-/+0.143 g/g, reaching
      the peak level at 15 min. CONCLUSION: Celecoxib can be rapidly absorbed through
      the tongue mucosa to reach a high concentration in the tongue tissue, indicating
      the possibility of oral COX-2 inhibitors to prevent oral cancer and precancerous
      lesions.

PMID- 20813677
TI  - [Short hairpin RNA-mediated MDC1 gene silencing enhances the radiosensitivity of
      esophageal squamous cell carcinoma cell line ECA109].
AB  - OBJECTIVE: To explore the effect of MDC1 gene silencing by RNA interference on
      the radiosensitivity of human esophageal carcinoma cell line ECA109. METHODS: The
      vectors containing short hairpin RNA (shRNA) targeting MDC1 gene (pMDC1-shRNA)
      were cotransfected with pPACKH1-lentivector packaging system into 293T cells to
      package the lentivirus particles. Forty-eight hours after the transfection with
      specific or control lentiviral vectors, the stable integrants were selected using
      copGFP reporter gene; real-time RT-PCR and Western blotting were used to detect
      the expression levels of MDC1 mRNA and protein in the transfected ECA109 cells,
      respectively. The cell cycle distribution was measured with flow cytometry at 12,
      24 and 48 h after a 5 Gy irradiation, and the radiosensitivity of esophageal
      carcinoma cell was evaluated by clone formation array. RESULTS: Sequence analysis
      confirmed correct insertion of MDC1-shRNA construct into pSIH1-H1-copGFP. The
      percentage of G2/M phase ECA109/ MDC1 cells was lower than that of ECA109 and
      ECA109/negative cells. The value of D0, SF2 and Dq of ECA109/ MDC1 cells were
      1.88 Gy, 0.84 and 1.20, respectively, lower than those of ECA109 cells (3.06 Gy,
      0.91 and 1.59) and those of ECA109/negative cells (2.90 Gy, 0.89 and 1.47).
      CONCLUSION: RNA interference can inhibit MDC1 gene expression and enhance the
      radiosensitivity of ECA109 cells in vitro.

PMID- 20813678
TI  - [Dorsal metatarsal artery distal perforator pedicle link-pattern flaps for wound
      repairing in the distal feet].
AB  - OBJECTIVE: To investigate the feasibility of repairing the wounds in the distal
      feet with dorsal metatarsal artery distal perforator pedicle link-pattern flaps.
      METHODS: Since January of 2004 to April of 2009, 30 patients with distal wounds
      in the feet underwent surgical wound repair using by dorsal metatarsal arteries
      distal perforator pedicle link-pattern flaps. Seventeen patients used the 1, 2
      dorsal metatarsal artery distal perforator flaps, and 13 had the 3, 4 dorsal
      metatarsal artery distal perforator flaps, with the flaps measuring 4 cmx4 cm to
      8 cmx7cm and the flap pedicle ranged 3-6 cm in length. The donor sites were
      repaired with skin grafting. RESULTS: Twenty-nine flaps survived completely and 1
      flap showed partial necrosis in the distant part (2.0 cmx1.0 cm). Twenty-one
      patients were followed up for an average of 11 months, during which the color,
      texture, and contour of the flaps remained normal without ulcers in the donor
      sites or the flaps. CONCLUSION: The wounds in the distal feet can be repaired by
      dorsal metatarsal artery distal perforator pedicle link-pattern flaps, which is a
      simple, applicable and safe procedure.

PMID- 20813679
TI  - [Association of CTLA4 gene +49G/A polymorphism with HBV infection and HBV-related
      hepatocellular carcinoma in Hunan Han population].
AB  - OBJECTIVE: To investigate the relationship between CTLA4 +49G/A SNP polymorphism
      and the susceptibility to hepatitis B virus (HBV)-related hepatocellular
      carcinoma (HCC). METHODS: CTLA4+49G/A single nucleotide polymorphism (SNP) was
      analyzed by DNA sequencing in 165 control subjects, 155 patients with chronic
      hepatitis B (CHB) and 149 HCC patients. Serum HBsAg, HBeAg and AFP levels were
      measured in all the subjects. RESULTS: In HCC and CHB groups, the genotype
      frequency was 40.3% and 50.0% for GG , and 59.7% and 50.0% for AG+AA,
      respectively, while the genotype frequency was 61.8% for GG and 38.2% for AG+AA
      in the control group. In HCC group, CHB group and controls, the A allele
      frequencies was 44.6%, 37.4% and 28.8%, and the G allele frequencies was 55.4%,
      62.6% and 71.2%, respectively. Significant differences were found not only in the
      allele frequencies (P<0.05) but also in AA and combined (AA+AG) genotype
      frequencies (P<0.05) between the 3 groups. CONCLUSION: +49G/A SNP of the CTLA4
      gene can be associated with HBV and HBV-related HCC.

PMID- 20813680
TI  - [Expression of recombinant extracellular region of human interleukin-1 receptor
      type I in Pichia pastoris].
AB  - OBJECTIVE: To construct pPICZalphaA-soluble interleukin-1 receptor type I (sIL
      1RI) recombinant expression vector containing the gene fragment encoding the
      extracellular domain of sIL-1RI for its expression in Pichia pastoris. METHODS:
      sIL-1RI gene was amplified by RT-PCR and inserted into the yeast expression
      vector pPICZalphaA by digestion ligation. The recombinant plasmid pPICZalphaA
      sIL1RI was transformed into E.coli Stb13, and the positive clones were analyzed
      by PCR and DNA sequencing. The pPICZalphaA-sIL1RI recombinant plasmid was
      electroporated into GS115 cells and the transformants were analyzed by PCR. After
      phenotype identification, the recombinant strains were induced by methanol to
      express the target protein, which was analyzed by Western blotting of the cell
      extract and supernatant. RESULTS: The recombinant plasmid pPICZalphaA-sIL-1RI was
      constructed successfully, and the results of Western blotting showed that yeast
      induced by methanol expressed a protein of about 39 kD. CONCLUSION: sIL-1RI
      protein has been successfully expressed in P.pastoris expression system, which
      provides the basis for further study of sIL-1RI.

PMID- 20813681
TI  - [Effect of intravenous lornoxicam at different doses on the immune function in
      patients undergoing total abdominal hysterectomy].
AB  - OBJECTIVE: To investigate the effect of intravenous lornoxicam (LOR) at different
      doses given preoperatively on the immune function of patients undergoing total
      abdominal hysterectomy (TAH). METHODS: Forty-five patients undergoing TAH were
      randomly divided into 3 groups, namely NS group, L8 group and L16 group with
      intravenous injection of 4 ml saline, 8 mg LOR, and 16 mg LOR before the
      induction of anesthesia respectively. Venous blood samples were taken before
      anesthesia (T0), at 30 min during the operation (T1), at the end of the operation
      (T2), and at 24 h and 48 h after the operation (T3 and T4, respectively) to
      determine the serum levels of regulated upon activation normal T cell expressed
      and secreted (RANTES), monocyte chemotactic protein-1 (MCP-1), and stromal cell
      derived factor 1 alpha (SDF-1alpha) by enzyme-linked immunosorbent assay (ELISA).
      RESULTS: The serum RANTES levels in NS group and L8 group at T1-T3 were
      significantly lower than those at T0 (P<0.05), but the levels in L8 group at each
      time point were all higher than those in NS group NS (P<0.05). The serum RANTES
      levels in L16 group L16 only decreased at T1-T2 as compared to those at T0, and
      were significantly higher than those in NS group and L8 group (P<0.05). The
      expressions of MCP-1 and SDF-1alpha in the 3 groups all increased at T1 and
      reached the peak levels after the operation. In L8 group and L16 group, MCP-1
      expression at T2-T3 and SDF-1alpha at T1-T2 were both significantly lower than
      those in NS group (P<0.05). SDF-1alpha expression at T1-T2 was significantly
      lower in L16 group than in L8 group (P<0.05). The decrements of MCP-1 and SDF
      1alpha were more obvious in L16 group than L8 group. CONCLUSIONS: Preoperative
      intravenous LOR injection may increase serum RANTES level and decrease MCP-1 and
      SDF-1alpha expressions to effectively relieve the perioperative immune disorders
      caused by TAH, and the effect is more potent at the dose of 16 mg.

PMID- 20813682
TI  - [Transfection of pancreatic cancer cells BxPC-3 with recombinant plasmid
      pSilencer4.1-CMV neo-hTERT-siRNA and its silencing effects].
AB  - OBJECTIVE: To study the transfection of pancreatic cancer cells BxPC-3 with
      recombinant plasmid pSilencer4.1-CMV neo-hTERT-siRNA and its silencing effects.
      METHODS: Pancreatic cancer cells BxPC-3 transfected with recombinant plasmid
      pSilencer4.1-CMV neo-hTERT-siRNA were selected as target and divided into five
      groups: (1) T1 group (pSilencer4.1CMV neo-hTERT1-siRNA), (2) T2 group
      (pSilencer4.1CMV neo-hTERT2-siRNA), (3) Lipofectamine (Lipofectamine), (4)
      mismatch group(pSilence4.1CMV, as negative control), (5) cell control
      group(without transfection). The expression of hTERT mRNA was detected by RT-PCR.
      The viability of cells was measured by MTT method. The cell cycle and cell
      apoptosis was measured by flow cytometry. The expression of telomerase protein
      was measured by Western blot. RESULTS: Compared with Lipofectamine group,
      negative control group and cell control group, the expression of hTERT-mRNA and
      telomerase protein in cells was downregulated significantly(P<0.05), the
      viability of BxPC-3 cells was decreased significantly (P<0.05), the ratio of
      cells in G0/G1 stage was increased, the ratio of cells in S stage and G2/M stage
      was decreased, and the ratio of apoptotic cells was increased significantly in T1
      group and T2 group. CONCLUSION: Recombinant plasmid T1 and T2 can downregulate
      the expression of hTERT mRNA and telomerase protein in BxPC-3 cells , and has
      good RNAi silencing effects. T1 and T2 can also inhibit the growth of BxPC-3
      cells, block the cell cycle, promote the apoptosis of cells, and has anti
      pancreatic cancer effects in vitro.

PMID- 20813683
TI  - [Norcantharidin inhibits DNA replication initiation protein Cdc6 in cancer
      cells].
AB  - OBJECTIVE: To explore the inhibitory effect of norcantharidin (NCTD) on the
      expression of DNA replication initiation protein Cdc6 in cancer cells. METHODS:
      MTT assay was performed to detect the inhibitory effect on different cancer cell
      lines, including HeLa, HepG2, Jurkat and Ramos cells. The effect of NCTD on Cdc6
      protein level was detected by Western blotting, and BrdU incorporation assay was
      used to evaluate the DNA replication of the cells. RESULTS: NCTD significantly
      inhibited the proliferation of the cells and caused degradation of Cdc6 protein
      to result in the inhibition of the DNA replication of the cells shown by BrdU
      incorporation assay. CONCLUSION: NCTD can induce the degradation of Cdc6 in
      cancer cells to produce an anti-cancer effect.

PMID- 20813684
TI  - [Expression of uncoupling protein 2 on macrophages and its relation to
      interleukin-10/interferon ratio in patients with unexplained recurrent
      spontaneous abortion].
AB  - OBJECTIVE: To investigate the relationship between the expression of uncoupling
      protein 2 (UCP2) and ratio of interleukin-10/interferon-gamma (IL10/IFNgamma) in
      the macrophages from patients with unexplained recurrent spontaneous abortion
      (URSA). METHODS: Twelve women undergoing selective termination of normal early
      pregnancy (control) and 11 having URSA were included in this study. Magnetic cell
      sorting (MACS) was used to isolate the macrophages in the decidua, and the
      expression of UCP2 was detected with flow cytometry. Cytokine (IL10 and IFNgamma)
      secretion by the macrophages was detected by enzyme-linked immunosorbent spot
      forming (ELISPOT) cell assay. RESULTS: Compared to the control group, the women
      with URSA showed significantly decreased expression of UCP2 on decidual
      macrophage (136-/+25 vs 201-/+31, P<0.01), and the expression of UCP2 was
      positively correlated to the ratio of IL10/IFNgamma(r=0.73, P<0.01). CONCLUSION:
      UCP2 may play an important role in the regulation of macrophage activity and
      cytokine secretion to contribute to spontaneous abortion.

PMID- 20813685
TI  - [Comparison of sevoflurane and propofol in combined anesthesia induction with
      remifentanil for tracheal intubation with fiberoptic bronchoscope].
AB  - OBJECTIVE: To compare the effect and hemodynamics of sevoflurane(SEV) and
      propofol (PRO) in combined anesthesia induction with remifentanil for tracheal
      intubation fibreoptic bronchoscope (FOB). METHODS: Twenty-four patients without
      difficult airway undergoing elective surgery with tracheal intubation general
      anesthesia were randomly divided into SEV and PRO group. FOB intubation was
      performed with sevoflurane or propofol administration combined with remifentanil
      induction. Blood pressure (BP), heart rate (HR), SPO2 and Narcotrend index (NI)
      were monitored to evaluate the anesthetic depth during the induction. The time to
      loss of consciousness (LOC), intubation time, intubation score, anesthetic dosage
      and adverse effects were recorded. RESULTS: No significant difference was found
      between the two groups in the time to LOC, intubation time, intubation score,
      remifentanil dosage. Intubation was performed successfully in both groups. BP and
      HR of both groups decreased after the induction and did not increase after the
      intubation, with variation within the normal range. No significant difference in
      BP and HR was found between the two groups. NI of both groups decreased after the
      induction and during intubation. NI of SEV group 2 min after intubation was
      higher than that of PRO group. There was no significant difference in NI between
      the two groups at the other time points. No significant adverse effects or recall
      of the intubation procedure were reported. CONCLUSION: Anesthesia induction FOB
      intubation with sevoflurane and propofol, both in combination with remifentanil,
      can be applied in surgical patients without contraindications to general
      anesthesia, and both methods can provide fast induction and good intubation
      condition with stable hemodynamics.

PMID- 20813686
TI  - [Relationship between muscle motor evoked potentials and hindlimbs motor function
      in rabbits with spinal cord injury].
AB  - OBJECTIVE: To study the relationship between muscle motor evoked potentials (MEP)
      and hindlimbs motor function in rabbits with spinal cord injury. METHODS: Forty
      five rabbits were randomly divided into 9 groups, including one control group and
      8 injured groups (receiving Allen's injury of 0, 50, 75, 100, 125, 150, 175, 200,
      or 250 gcf). Hindlimb strength and muscle MEP were recorded at the 1st day and
      4th week postoperatively. At 4 weeks after spinal section, the spinal cord tissue
      was sampled for histological examination with HE staining and
      immunohistochemistry with anti-NF antibody of the corticospinal tract fibers.
      RESULTS: During the operation, MEP showed an all-or-none pattern with significant
      correlations to postoperative optical density of NF and postoperative hindlimb
      motor function. The latency prolongation of the muscle MEP at the 4th week showed
      a linear correlation to the hindlimb Tarlov's score, whereas the MEP amplitude
      was not correlated to postoperative hindlimb motor function. CONCLUSIONS: The all
      or-none pattern of muscle MEP can be used to evaluate the severity of spinal cord
      injury.

PMID- 20813687
TI  - [Morphological investigation of the protective effect of astragaloside
      preconditioning against ischemia-reperfusion lung injury in rats].
AB  - OBJECTIVE: To study the protective mechanisms of the astragaloside against
      ischemia-reperfusion lung injury in rats. METHODS: Ischemia-reperfusion lung
      injury was induced in SD rats. Astragalus armour glucoside was dissolved in 1% of
      sodium carboxymethyl cellulose at different concentrations (8, 6, and 3 mg/ml)
      was intragastrically administered in the rats at the dose of 1 ml/100 g. Cellular
      and subcellular structural changes in the lung tissue were observed at the end of
      the experiment using optical and transmission electron microscope, with the
      wet/dry ratio of the lung tissue and myeloperoxidase (MPO) activity measured.
      RESULTS: The wet/dry ratio and myeloperoxidase activity in the lung tissue were
      significantly higher in the model group than in the sham-operated group (P<0.05),
      and were significantly lowered by the treatment with astragalus armour glucoside
      at different doses (P<0.01 or 0.05), and the effect was especially obvious in
      rats receiving a moderate dose. Pulmonary capillary expansion, erythrocyte
      leakage and exudate in the alveolar space with obvious pathological changes in
      the type I and II epithelial cells were observed in model group. Pulmonary
      capillary expansion was reduced in rats treated with high, medium and low dose of
      Astragalus armour glucoside, and the medium dose group showed the most obvious
      effect, in which no edema fluid in the alveolar space or erythrocyte leakage was
      found with also reduced type II lung epithelial cell degranulation. CONCLUSION:
      Astragaloside has obvious antioxidant effect in rats with ischemia-reperfusion
      lung injury, and a medium dose produces the best effect.

PMID- 20813688
TI  - [Dynamic observations of beta-catenin in chronic myeloid leukemia and its
      relationship with cytogenetic response].
AB  - OBJECTIVE: To investigate the changes in the expression of beta-catenin in
      patients with chronic myeloid leukemia (CML) in different phases, and explore the
      relationship between beta-catenin and the cytogenetic response to imatinib
      mesylate. METHODS: Beta-catenin mRNA and protein expressions were detected by RT
      PCR and Western blotting in the bone marrow mononuclear cells (BMMNCs) from 99
      CML patients. The expressions of BCR-ABL fusion gene at both the mRNA and protein
      levels were detected by fluorescence in situ hybridization (FISH) in 94 patients
      before and during the one-year treatment with imatinib mesylate at the interval
      of 3 months, and the relationship between beta-catenin and cytogenetic response
      to imatinib mesylate was analyzed. RESULTS: The expression of beta-catenin
      increased significantly in patients with blast crisis and accelerated phase
      (P<0.001), but showed no significant difference between normal subjects and CML
      patients in the chronic phase (P>0.05). The main cytogenetic remission rate was
      significantly higher in patients who were consistently negative for beta-catenin
      than in those consistently positive for beta-catenin or those with a positive
      transformation (P<0.001). CONCLUSION: Beta-catenin overexpression in the
      progression of CML, consistent high level of beta-catenin or a positive
      transformation may indicate a poor response to imatinib, and early measures
      should be taken to increase the remission rate.

PMID- 20813689
TI  - [Mechanism of oxymatrine in preventing hepatic fibrosis formation in patients
      with chronic hepatitis B].
AB  - OBJECTIVE: To explore the mechanism of oxymatrine in preventing hepatic fibrosis
      formation in patients with chronic hepatitis B (CHB). METHODS: A total of 80 CHB
      patients receiving routine therapies for liver protection and support were
      divided into two groups. Oxymatrine at the daily dose of 150 mg was injected
      intravenously in the therapeutic group (n=40), and gluthion (1.2 g daily) was
      injected in the control group (n=40) for 8 weeks. The liver functions, indexes of
      hepatic fibrosis and the levels of transforming growth factor-beta1 (TGF-beta1),
      tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) were measured
      in these patients before and after the therapy. RESULTS: Liver functions was
      obviously improved after therapy in both groups, showing no significant
      difference between them (P>0.05). The indexes of hepatic fibrosis such as HA, LN,
      PCIII and C-IV were significantly lower in the therapeutic group than in the
      control group (P<0.01). The serum levels of TGF-beta1 and TNF-alpha decreased
      while IL-10 increased significantly after the treatment in the therapeutic group
      (P<0.05). CONCLUSION: The effect of oxymatrine against hepatic fibrosis is
      mediated by lowering the levels of TGF-beta1 and TNF-alpha and increasing the
      level of IL-10 in CHB patients.

PMID- 20813690
TI  - [Effect of sinomenine on tumor necrosis factor-alpha and nuclear factor-kappaB in
      the heterotopic tissue in rats with endometriosis].
AB  - OBJECTIVE: To investigate the effect of sinomenine on the level of tumor necrosis
      factor-alpha (TNF-alpha) and nuclear factor-kappaB (NF-kappaB) and in the
      heterotopic tissue in rats with endometriosis. METHODS: The rats with
      endometriosis were divided into sinomenine lavage group, blank control group,
      model group and danazol group, and the levels of TNF-alpha and NF-kappaB in the
      heterotopic tissues of the rats were detected with immunohistochemistry. RESULTS:
      Sinomenine lavage and danazol treatment both significantly decreased the levels
      of levels of TNF-alpha and NF-kappaB in the heterotopic tissues of the rats as
      compared with the model group (P<0.05), and lesions were significantly smaller in
      sinomenine lavage group than in danazol group. CONCLUSION: Sinomenine can inhibit
      the production and activity of TNF-alpha and NF-kappaB to suppress the adhesion,
      implantation, infiltration and growth of the endometrial cells in the rat model
      of endometriosis.

PMID- 20813691
TI  - [Relationship between Tpeak-Tend interval and coronary artery stenosis and
      effects of percutaneous transluminal coronary angioplasty on Tpeak-Tend].
AB  - OBJECTIVE: To explore the relationship between Tpeak-Tend interval (Tpe) and the
      extent and severity of coronary artery stenosis, and evaluate the effect of
      percutaneous transluminal coronary angioplasty and stent implantation (PCI) on
      Tpe in the patients with coronary heart disease (CHD). METHODS: The ECG data were
      collected from 187 CHD patients undergoing coronary angiography and PCI to
      evaluate the extend and severity of coronary artery stenosis before and after the
      interventions. RESULTS: The Tpe of patients with severe stenosis increased
      significantly as compared with that in patients with moderate stenosis (138.9
      /+16.2 ms vs 116.5-/+13.7 ms, P<0.05), and a significant difference was also
      noted between the moderate stenosis and mild stenosis (86.4-/+12.9 ms) groups
      (P<0.05). The Tpe decreased significantly in the patients in the order of multi
      vessel involvement (140.7-/+17.8 ms), double vessel involvement (118.6-/+14.9
      ms), singly vessel involvement (100.5-/+13.2 ms), and stenosis-free (84.3-/+12.4
      ms) groups (P<0.05). Tpe was correlated to the extent and severity of coronary
      artery stenosis (r>0.4). In patients with severe stenosis, the Tpe was
      significantly reduced at 1 h, 24 h, and 1 week after PCI (115.8-/+14.5, 92.7
      /+12.9, and 88.2-/+11.3 ms, respectively, P<0.05). CONCLUSION: The Tpe can
      reflect the severity and range of coronary artery stenosis, which can be reduced
      by PCI. Tpe can be a new index for evaluating myocardial ischemia in CHD
      patients.

PMID- 20813692
TI  - [Epidemiological and etiologic characteristics of ocular fungal infection in
      Haikou].
AB  - OBJECTIVE: To analyze the epidemiological and etiologic characteristics of ocular
      fungal infection in Haikou. METHODS: The samples of corneal, conjunctivae,
      anterior chambers, lacrimal sacs were taken from the outpatients and inpatients
      in the Department of Ophthalmology for fungal culture. The positivity rates of
      fungal culture were statistically analyzed to describe the seasonal and genus
      distribution of the fungal infections. RESULTS: A total of 683 patients were
      involved in this study, and the total positivity rate of fungal culture was
      27.96%. The positivity rate was 33.42% in male patients and 21.52% in female
      patients (P<0.01). The positivity rates were 31.42%, 11.32%, 10.81%, 21.28% and
      29.17% in the cornea, conjunctivae, anterior chambers, lacrimal sacs and other
      locations (P<0.01), and were 34.88%, 22.58%, 11.76%, 4.11%, 21.43% and 13.33% in
      farmers, workers, teachers, government officers, students and personnel of other
      occupations (Chi2=39.550, P=0.001), respectively. In terms of age, the rate was
      32.30% in 21-40 years group, 31.72% in 41-60 years group, 17.12% in over 60 years
      group and 26.61% in below 20 years group, showing significant differences
      (P<0.01). The rates were higher in August, September, October, December,
      November, all above 30%, but lower in March. Nine genera were identified,
      including Candida (49.21%), Aspergillus (19.37%), Fusarium (9.42%), mucor
      (5.76%), Actinomyces (5.24%), Penicillium (3.66%), Saccharomyces (2.62%), non
      spore group (1.57%), Alternaria (1.57%), and other genera (1.57%). Among the 94
      strains of Candida, 63 (67.02%) belonged to Candida albicans and 14 to Candida
      tropicalis (14.89%). CONCLUSION: Ocular fungal infection occurs more often in
      male patients and in the cornea. The common pathogen of ocular fungal infection
      is Candida, which is different from the etiological characteristics in other
      areas possibly in association with the tropical climate.

PMID- 20813693
TI  - [Expression of P27kip1 in renal cell carcinoma and its clinical significance].
AB  - OBJECTIVE: To investigate the expression of cyclin-dependent kinase inhibitor
      p27kip1 in renal cell carcinoma and its clinical significance. METHODS: The
      expressions of p27kip1 mRNA and protein were evaluated using reverse
      transcription polymerase chain reaction (RT-PCR), Western blotting and
      immunohistochemistry with tissue chip technique in renal cell carcinoma (RCC)
      tissues, adjacent tissues and 786-0 cell line. The relationship between the
      expression of p27kip1 and the tumor size, the clinical stage, pathological type
      and stage were evaluated, and the results by the 3 methods were analyzed to
      evaluate the relationship between the mRNA and protein of p27kip1. RESULTS: The
      expression of p27kip1 protein (detected by immunohistochemistry and Western
      blotting) in RCC tissue was significantly lower than that in the adjacent normal
      tissues (P<0.05). The expression of p27kip1 mRNA (by RT-PCR) showed no
      significant difference between the two groups. p27kip1 protein expression was
      found to be inversely correlated to the tumor grade and clinical stage (P<0.05).
      Western blotting and immunohistochemistry showed a high coincidence rate in the
      detection of P27kip1 protein expression in RCC samples (P<0.001, K=0.828).
      CONCLUSION: p27kip1 mRNA expression shows no difference between RCC and normal
      tissues, while the protein expression is significantly lower in the cancer
      tissues, suggesting a regulatory mechanism of p27kip1 expression at the
      transcriptional level. Low expression of p27kip1 protein may promote the
      development and progression of RCC. p27kip1 protein may serve as a diagnostic and
      prognostic marker of RCC.

PMID- 20813694
TI  - [Construction of recombinant adenovirus containing TK gene and its effect against
      human liver cancer cells].
AB  - OBJECTIVE: To construct a replication-defective adenovirus containing TK gene and
      investigate the killing effects of TK gene against human liver cancer cells SMMC
      7721. METHODS: The recombinant adenovirus ADV-TK was constructed using homologous
      recombination in the cells. SMMC-7721 cells transfected with recombined
      adenovirus were exposed to GCV, and the cell viability was measured by MTT
      assays. RESULTS: The recombinant adenovirus containing TK gene was successfully
      constructed. Transfection by the recombinant adenovirus ADV-TK and GCV exposure
      significantly suppressed the growth of SMMC-7721 cells. CONCLUSION: A replication
      defective adenovirus containing TK gene has been successfully constructed, and in
      combination with GCV, the recombinant adenovirus produces significant killing
      effect against SMMC-7721 cells in vitro.

PMID- 20813695
TI  - [Correlation of angiotensin-converting enzyme 2 gene polymorphisms to essential
      hypertension and ischemic stroke].
AB  - OBJECTIVE: To study the relationship between angiotensin-converting enzyme 2
      (ACE2) gene polymorphisms and the risk factor for essential hypertension (EH)
      with concurrent ischemic stroke in southern Chinese population. METHODS: The
      G9570A polymorphism in ACE2 gene were detected in 139 patients with EH and stroke
      using polymerase chain reaction-restriction fragment length polymorphism.
      Detailed clinical and biochemistrical data of the patients, including the pulse
      pressure, high sensitivity C-reactive protein (hsCRP), intima-media thickness
      (IMT), high-density lipoprotein cholesterol (HDL-C) and uric acid levels, were
      collected to study the relationship between ACE2 gene and the risk factor of EH
      and stroke. RESULTS: The levels of hsCRP (OR=1.022), uric acid (OR=1.224), IMT
      and pulse pressure was positively correlated to the incidence of EH and stroke.
      The pulse pressure, hsCRP, IMT, and HDL-C levels in male stroke patients carrying
      A allele was significantly higher than those in patients carrying G allele
      (P<0.05). In female stroke patients, the pulse pressure, hsCRP, IMT, and HDL-C
      levels were also significantly different with regard to the genotype of ACE2 gene
      (P<0.05). CONCLUSIONS: The patients with EH and ischemic stroke carrying the A/AA
      allele of ACE2 gene have higher risks than those carrying other allele, and can
      be also more vulnerable to stroke recurrence.

PMID- 20813696
TI  - [Correlation of CKP and VEGF expression and microvessel density to spiral CT
      manifestations of thymoma].
AB  - OBJECTIVE: To investigate the correlation of cytokeratin pan (CKP), vascular
      endothelial growth factor (VEGF) expression and microvessel density (MVD) to
      spiral CT manifestations of thymoma. METHODS: Eighty-four thymoma patients were
      underwent spiral CT examination, and 40 of the patients also had enhanced CT
      examination. All the CT findings were carefully reviewed to analyze their
      correlation to the expressions of CKP, VEGF and MVD. RESULTS: The enhancement on
      spiral CT images increased with the levels of VEGF expression and MVD counting
      (P<0.01). Significant correlations were observed between VEGF expression, MVD
      counting and such spiral CT findings as lobular contours, cusp-like or sawtooth
      like margins and tumor invasions of the pleural membrane, pericardium and great
      vessels (P<0.05). CKP expression showed no obvious correlation to these findings
      by spiral CT. CONCLUSION: Spiral CT can reflect the pathological characteristics
      of thymoma, and may serve as a noninvasive modality for preoperative evaluation
      of thymoma.

PMID- 20813698
TI  - [Transrectal high-intensity focused ultrasound for treatment of benign prostatic
      hyperplasia: report of 262 cases].
AB  - OBJECTIVE: To explore the application of transrectal high-intensity focused
      ultrasound (HIFU) for treatment of benign prostatic hyperplasia (BPH). METHODS:
      From Dec. 2002 to Dec. 2006, 262 BPH patients underwent transrectal HIFU ablative
      therapy. After the treatment, IPSS, QOL score, peak uroflow rate and prostatic
      volume measured by TRUS were used for evaluation. RESULTS: After 1 to 3 years'
      follow-up, IPSS, QOL score, and prostatic volume all decreased, while the peak
      uroflow rate increased obviously (P<0.01). Mild hematuria was noted in all the
      cases after the treatment, and epididymitis was found in 7 cases (2.7%), short
      term hematospermia in 66 cases (25.2%), retrograde ejaculation in 35 cases
      (13.4%), and urethro-rectal fistula in 1 case (0.3%). No urinary incontinence was
      found in these cases. TURP was performed in 18 cases (6.8%) in 3 years after the
      treatment due to an excessively large volume of the prostates or bladder neck
      contracture. CONCLUSION: HIFU is effective and safe in the treatment of BPH which
      causes minimal invasion, absence of intraoperative bleeding, good tolerance and
      few complications, and is especially suitable in elderly patients.

PMID- 20813697
TI  - [Endostatin in different administration routes combined with adriamycin
      chemotherapy in the treatment of liver cancer xenograft in mice].
AB  - OBJECTIVE: To study the antiangiogenetic and tumor inhibitory effects of
      endostatin (Es) by intratumoral versus intravenous administration combined with
      adriamycin (Adm) for treatment of transplanted tumor in mice. METHODS: Forty mice
      were subjected to subcutaneous implantation of H22 cells and randomly divided
      into 4 groups by the body weight when the tumor diameter reached 1 cm, namely the
      control group (with intratumoral and intravenous injection of normal saline), Es
      intratumoral group (with intratumoral injection Es and intraperitoneal Adm
      injection), Es vein group (with intravenous Es injection and intraperitoneal Adm
      injection), and Adm group (with intratumoral saline injection and intraperitoneal
      Adm injection). The tumor volumes and tumor inhibition rates were calculated, and
      the expression of vascular endothelial growth factor (VEGF) and the microvessel
      density (MVD) of the tumors were examined, with the survival time of the mice
      also observed. RESULTS: The tumor volume was smaller in Es intratumoral group
      than in the other groups (P<0.05). The expression of VEGF and M VD in Es
      intratumoral group was significantly decreased as compared with that in the other
      groups (P<0.05). The survival time was significantly longer in Es intratumoral
      group and Es vein group than in the other groups (P<0.05), but showed no
      significant difference between Es intratumoral group and Es vein group (P>0.05).
      CONCLUSION: In combination with Adm regimen, Es given intratumoral injection
      produces better effect than intravenous Es injection against angiogenesis and
      tumor growth, no significant difference can be found in the survival time between
      them.

PMID- 20813699
TI  - [Application of immunohistochemical labeling in the diagnosis of hepatobiliary
      intraepithelial neoplasia and/or cancer].
AB  - OBJECTIVE: To investigate the best combination of monoclonal antibodies for the
      diagnosis of hepatobiliary intraepithelial neoplasia and/or cancer. METHODS: CK7,
      CK20, Villin, CEA, P53 and Ki-67 antigens were detected in the tissues of high
      level hepatobiliary intraepithelial neoplasia and cancer by immunohistochemistry
      and the results were analyzed statistically. RESULTS: Villin was 100% positive in
      hepatobiliary intraepithelial neoplasia and/or cancer, while 100% negative in the
      adjacent normal bile duct epithelium. The expression rate of CEA was
      significantly lower in high-level hepatobiliary intraepithelial neoplasia tissues
      than in the cancer tissues (P<0.05). Ki-67 indexes were significantly lower in
      most of the high-level hepatobiliary intraepithelial neoplasia than in the cancer
      tissue (P<0.01). P53 indexes were also lower in high-level hepatobiliary
      intraepithelial neoplasia (P<0.01). CONCLUSION: Detection of multiple antigens
      (CEA, Villin, Ki-67 and P53) provides specific clues to the diagnosis of high
      grade hepatobiliary intraepithelial neoplasia and/or cancer.

PMID- 20813700
TI  - [Relationship between liver damage and serum levels of IL-18, TNF-alpha and NO in
      patients with acute pancreatitis].
AB  - OBJECTIVE: To study the relationship between liver damage and the serum levels of
      interleukin-18 (IL-18), tumor necrosis factor-alpha (TNF-alpha) and NO in
      patients with acute pancreatitis (AP). METHODS: Eighty-seven AP patients were
      divided into mild AP (MAP) and severe AP (SAP) groups, with 50 healthy subjects
      serving as the controls. The serum levels of IL-18 and TNF-alpha were determined
      by ELISA, and NO level was measured by nitrate reductase method. The serum levels
      of ALT, AST, TB, ALB, LDH, AKP and gamma-GT were also measured. RESULTS: The
      incidence of liver damage was 62.06% in these patients. The serum markers of the
      liver function differed significantly between the AP patients and the control
      subjects and between SAP and MAP groups before the treatment (P<0.01). The ALB
      level in SAP group increased significantly after the treatment (P<0.01), and the
      other indices of the liver function all decreased in both MAP and SAP groups
      (P<0.01). The serum levels of IL-18, TNF-alpha and NO were higher in the AP
      patient than in the control subjects (P<0.01), and decreased significantly after
      the treatment (P<0.01). In AP patients with liver damage, the levels of IL-18,
      TNF-alpha and NO were obviously higher than those in patients without liver
      damage and the control group (P<0.01). In AP patients with liver damage, the
      serum levels of IL-18, TNF-alpha, and NO were positively correlated to ALT and
      AST levels, and IL-18 was positively correlated to TNF-alpha and NO. CONCLUSION:
      AP patients have high incidence of liver damage, which is obviously severer in
      SAP than in MAP patients. The serum levels of IL-18, TNF-alpha and NO are
      positively correlated to the severity of liver damage in the AP patients, and can
      be used as indicators for early diagnosis, evaluation of the severity and
      prognosis of liver damage.

PMID- 20813701
TI  - [Pathological classification and clinical characteristics of lupus nephritis: a
      report of 49 cases].
AB  - OBJECTIVE: To evaluate the relation between the pathological features of lupus
      nephritis (LN) and the clinical activity and laboratory examination. METHODS:
      Renal biopsies were obtained from 49 cases of lupus nephritis and classified
      according to ISN/RPS(2003) classification. The clinical activity, laboratory
      results and the renal pathological features of the disease were analyzed.
      RESULTS: All the cases showed pathologies in the kidney. Type IV and V LN cases
      had a high incidence of nephrotic syndrome, and type II and III cases frequently
      showed latent nephritis. The NIH index and biopsy index indicated the degree of
      pathological lesions and were significantly related to the clinical features.
      Nearly all the indexes including NIH index, biopsy index, the clinical activity
      and the laboratory examination suggested stronger activity of type IV LN than the
      other types. CONCLUSION: The pathological changes, clinical activity and
      laboratory examination results of LN are related with each other. The clinical
      activity and laboratory examination of LN can be used to estimate the
      pathological type and degree of renal lesion in LN.

PMID- 20813702
TI  - [Continuous versus intermittent azithromycin administration for treatment of
      Mycoplasma pneumonia-induced pneumonia: effects and drug resistance in rats].
AB  - OBJECTIVE: To evaluate the efficacy and drug resistance of azithromycin
      administered via continuous infusion versus intermittent administration in rats
      with Mycoplasma pneumonia-induced pneumonia. METHODS: Pneumonia was induced in
      rats by intranasal administration of mycoplasma suspension. The rats with
      established pneumonia were randomly divided into continuous and intermittent
      infusion groups with intraperitoneal azithromycin injection on a daily basis for
      6 consecutive days, or for 3 consecutive days followed by a 3-day rest (which was
      repeated twice), respectively. The bronchoalveolar lavage (BAL) and venous blood
      were collected before and at 3, 6, 9, and 12 days during or after the treatments
      for MIC test. The rats were killed for lung pathological examination, and the
      plasma samples were obtained for drug assays by HPLC. RESULTS: Pathological
      examination of the lungs demonstrated better improvement in the intermittent
      group than in continuous group. At 12 days of the treatment, the MIC value was
      higher in the continuous group than in the intermittent group. CONCLUSION:
      Intermittent azithromycin administration produces better therapeutic effect
      against Mycoplasma pneumonia than continuous drug delivery in rats with less
      likeliness of inducing drug resistance.

PMID- 20813704
TI  - [Application of nonlinear mixed models in Logistic regression with random effect
      in clinical trials].
AB  - OBJECTIVE: To explore the application of nonlinear mixed models fitting logistic
      regression in clinical trials. METHODS: Two clinical trials were selected to
      exemplify the method for fitting nonlinear logistic regression using nonlinear
      mixed models by running NLMIXED procedure in SAS. RESULTS: All the parameters and
      their standard errors were estimated, and each factor could be properly
      interpreted. CONCLUSION: Nonlinear mixed models in which both fixed and random
      effects enter nonlinearly can fit nonlinear logistic regression. These models
      provide effective methods to analyze the binary data in clinical trials.

PMID- 20813703
TI  - [Fertilization rates following 109 half intracytoplasmic sperm injection cycles
      for in vitro fertilization-embryo transfer].
AB  - OBJECTIVE: To evaluate the clinical outcomes of half intracytoplasmic sperm
      injection (partial ICSI) treatment in infertile patients with potential
      fertilization failure. METHODS: A total of 109 partial ICSI cycles of in vitro
      fertilization-embryo transfer (IVF-ET) were classified into 5 groups, namely
      group A (infertile patients for unidentified causes, 17 cycles), group B (oligo
      asthenozoospermia patients, 28 cycles), group C (teratozoospermia patients, 8
      cycles), group D (primary infertile patients without definite causes, 31 cycles),
      and group E (secondary infertile patients without definite causes, 25 cycles).
      The fertilization rate and normal fertilization rate after IVF and ICSI were
      compared between the groups. RESULTS: Significant differences were found in the
      fertilization rate following conventional IVF and ICSI in group A (53.1-/+38.8%
      vs 72.2-/+34.1%) and group D (58.8-/+31.6% vs 82.7-/+21.4%) (P<0.05), but not in
      groups B, C and E (P>0.05). The normal fertilization rates following IVF and ICSI
      in groups A, B, D, E were statistically different (P<0.05), but similar in group
      C (P>0.05). CONCLUSION: ICSI treatment may increase the fertilization rate of IVF
      ET in patients with unexplained infertility and primary infertility, but not in
      patients with oligo-asthenozoospermia, teratozoospermia or secondary infertility.

PMID- 20813705
TI  - [Effect of continuous hemofiltration for treatment of multiple organ dysfunction
      syndrome after acute myocardial infarction in elderly patients].
AB  - OBJECTIVE: To study the effect of continuous hemofiltration (CH) on the prognosis
      of multiple organ dysfunction syndrome (MODS) after acute myocardial infarction
      (AMI) in elderly patients. METHODS: Thirty-four elderly patients with MODS after
      AMI admitted to intensive care unit (ICU) were grouped into continuous
      hemofiltration (CH) group and non-CH (NCH) group. The Acute Physiology and
      Chronic Health Evaluation (APACHEII) scores and Marshall scores were assessed
      upon admission in ICU and 7 days after the admission. The mortality rates of the
      patients within 28 and 90 days after admission to ICU were calculated, and the
      changes in APACHEII scores and Marshall scores were compared between the two
      groups. RESULTS: The APACHEII scores and Marshall scores showed no significant
      difference between the two upon admission to the ICU, but significantly decreased
      in CH group 7 days after the admission (P<0.05 and P<0.01 respectively). The
      APACHEII scores increased significantly in NCH group (P<0.01) 7 days after the
      admission while the Marshall scores remained unchanged (P>0.05). The overall
      mortality rates at 28 and 90 days were 41.18% and 61.76%, respectively. A
      significant difference was noted in the mortality rate at 28 days between the two
      groups (P<0.05), but not in the rate at 90 days (P>0.05). CONCLUSION: CH can
      improve the organic functions and the short-term outcome of elderly patients with
      MODS after AMI, but has no positive effect on their long-term outcomes.

PMID- 20813706
TI  - [Therapeutic efficacy of Nexavar on liver cancer and its relation to the
      expression of Ki-67 and CD34].
AB  - OBJECTIVE: To study the therapeutic effects of Nexavar on liver cancer and its
      relation to the expressions of Ki-67 and CD34. METHODS: Twenty-eight patients
      with liver cancer were treated with Nexavar. The therapeutic efficacy of Nexavar
      on liver cancer was observed. Liver cancer tissues were examined for the
      expressions of Ki-67 and CD34 by immunohistochemistry. Microvessel density (MVD)
      was calculated according to the expression of CD34. RESULTS: Of 28 patients, none
      achieved a complete response (CR), 12 had a partial response (PR), 7 had stable
      disease (SD), and 9 progressive disease (PD). The efficacy of Nexavar was
      associated significantly with Ki-67 expression. The mean MVD count was 346.03
      /+146.98 in PR patients, and 89.14-/+45.66 in PD patients. There was a
      significant difference in MVD between PR and PD patients. CONCLUSION: There is a
      better efficacy of Nexavar in treatment of liver cancer in the patients who had
      Ki-67-positive expression and high MVD count.

PMID- 20813707
TI  - [Retroperitoneal laparoscopic living donor nephrectomy: report of 58 cases].
AB  - OBJECTIVE: To review a single-institution experience with retroperitoneal
      laparoscopic living donor nephrectomy (RLDN). METHODS: Fifty-eight donors
      underwent RLDN at our institution (including 32 male and 26 female donors aged 20
      61 years, mean 42 years). Left nephrectomy was performed in 56 cases. The first
      35 patients underwent total RLDN, and the latter 23 received modified RLDN.
      RESULTS: RLDN was performed successfully in all the patients without conversion
      to open surgery. The mean surgical time was 93 min (range 70-130 min), and the
      mean blood loss was 20 ml (range 10-50 ml), with a mean warm ischemia time of 2.8
      min (1.3-6 min). Retroperitoneal hematoma occurred postoperatively in one case.
      The mean hospital stay of the donors was 6.4 days (5-10 days). Two recipients
      showed delayed graft function, and one graft was lost because of acute rejection.
      The other recipients had normal renal function in two weeks except for 3 having
      normal renal function in 4 weeks. CONCLUSION: RLDN is a safe procedure with
      minimal invasiveness, and the modified RLDN lowers the learning curve of the
      surgery.

PMID- 20813708
TI  - [Effects of metformin on proliferation of human colon carcinoma cell line SW
      480].
AB  - OBJECTIVE: To observe the effect of metformin on the proliferation of SW-480
      cells and study the possible mechanism. METHODS: The proliferation of SW-480
      cells treated with different concentrations of metformin was assessed by MTT
      assay, and the cell cycle changes were analyzed by flow cytometry. The expression
      of cyclin D1 in the treated cells was detected by Western blotting, and
      telomerase activity examined by telomeric repeat amplification protocol (TRAP)
      silver staining. RESULTS: Metformin decreased the proliferation of SW-480 cells
      in a dose- and time-dependent manner. The proportion of the cells at G0/G1 stage
      in the control and metformin-treated (5 mmol/L, 72 h) cells was (55.81-/+0.63)%
      and (63.38-/+0.99)%, the cell proportion at S stage was (31.11-/+3.05)% and
      (25.29-/+1.64)%, and that at G2/M stage was (13.09-/+3.00)% and (11.33-/+2.60)%,
      respectively. The expression of cyclin D1 in metformin-treated cells were lowered
      significantly as compared with that in the control cells. Telomerase activity was
      also decreased significantly in the cells after treatment with 5 mmol/L metformin
      for 72 h. CONCLUSION: Metformin can inhibit the growth of SW-480 cells mainly by
      blocking the cell cycle at G0/G1, down-regulating the expression of cyclin D1 and
      decreasing telomerase activity.

PMID- 20813709
TI  - [Construction and identification of blood type B antigen mimetic polypeptide
      Mip3beta double expression recombinant plasmid].
AB  - OBJECTIVE: To construct and identify blood type B antigen mimetic polypeptide
      macrophage inflammatory protein 3beta (Mip3beta) double expression recombinant
      plasmid. METHODS: The positive phage clone P1 was obtained using phage random 12
      mer peptide library. Specific primers were designed to amplify the phage DNA of
      P1 and transmembrane domain and inner segment of PBluscript-Fas gene. The
      products of the amplification were linked into Mip3betav21 to construct blood
      type B antigen mimetic polypeptide-Mip3beta double expression recombinant
      plasmid. The recombinant plasmid was transfected into human melanoma cell line
      B16 to identify its expression. RESULTS AND CONCLUSION: Blood type B antigen
      mimetic polypeptide-Mip3beta double expression recombinant plasmid is
      successfully obtained and expressed in human melanoma cell line B16.

PMID- 20813710
TI  - [Value of 16-slice spiral CT in the diagnosis of tumor-like bronchial
      tuberculosis].
AB  - OBJECTIVE: To evaluate the value of 16-slice multi-detector CT (MDCT) in the
      diagnosis of tumor-like bronchial tuberculosis. METHODS: Twenty-five patients
      with tumor-like bronchial tuberculosis underwent 16-slice CT scanning and the CT
      data were analyzed. RESULTS: Tumor-like bronchial tuberculosis were classified
      into 4 types according to the imaging features, namely intra-lumen nodule, intra
      lumen mass, compression from outside of the bronchial lumens, and lung hilum
      mass. Tumor-like bronchial tuberculosis was featured by irregular bronchial wall
      thickening which led to decreased internal diameter of the bronchi with the
      external diameter remaining unchanged, ring-shaped enhancement, and absence of
      clear boundaries between the lesion and normal bronchi. CONCLUSION: 16-slice MDCT
      can be advantageous in displaying tumor-like bronchial tuberculosis, and axial
      scan with 16-slice spiral CT combined with image reconstruction allows detection
      of the lesions inside the trachea and bronchus.

PMID- 20813711
TI  - [Establishment of a rabbit model of congestive heart failure].
AB  - OBJECTIVE: To study the feasibility of establishing a rabbit model of congestive
      heart failure model by abdominal aortic coarctation combined with intravenous
      epinephrine infusion. METHODS: Twenty rabbits were randomized into the study
      group (n=10) and control group (n=10). Congestive heart failure was induced in
      the study group by abdominal aortic coarctation combined with intravenous
      epinephrine infusion. The diameter of the abdominal aorta was reduced by 50%-60%,
      and epinephrine was infused at 2 weeks (5 mg.kg(-1).min(-1) for 60 min), 4 weeks
      (4 mg.kg(-1).min(-1) for 60 min) and 6 weeks (4 mg.kg(-1).min(-1) for 60 min)
      after the operation. The changes in the systolic and diastolic functions of the
      rabbits were assessed by echocardiography and catheterization during the
      progression of left hypertrophy. RESULTS: The diameter of the abdominal aorta at
      the coarctation region was 4.87-/+0.53 mm before the operation, reduced to 2.26
      /+0.47 mm after the operation. At 8 weeks after the operation, the hearts of the
      rabbits in the study group showed obvious abnormalities in echocardiography,
      while the hearts in the control group remained normal. CONCLUSION: Abdominal
      aortic coarctation combined with intravenous epinephrine infusion allows rapid
      establishment of a reliable rabbit model of chronic congestive heart failure.

PMID- 20813712
TI  - [Expression of glucose transporter-3 in the cerebral cortex of aging rats].
AB  - OBJECTIVE: To observe the changes in the expression of glucose transporter-3
      (GLUT3) in the cerebral cortex of rats during aging and investigate the role of
      GLUT3 in the aging process of the nervous system. METHODS: The cerebral tissues
      were collected from rats of 3, 18, 24, and 30 months old (10 in each age group),
      and the expression of GLUT3 in the cerebral cortex was detected by
      immunohistochemistry. RESULTS: Under optical microscope, GLUT3-positive cells
      were found in every group. Within the age range of 3 to 8 months, GLUT3-positive
      cells increased significantly with age (P<0.01), but at 24-30 months of age, the
      number of GLUT3-positive cells reduced significant with age (P<0.01). CONCLUSION:
      The expression changes of GLUT3 ir the cerebral cortex of rats during aging
      indicate that GLUT3 plays an important role in the maturation and aging of the
      nervous system.

PMID- 20813713
TI  - [Efficacy of water knife needle release combined with bone peptide injection for
      heel pain].
AB  - OBJECTIVE: To evaluate the efficacy of water knife needle release combined with
      bone peptide injection in the management of heel pain. METHODS: Thirty-five
      patients with unilateral heel pain were treated with water knife needle release
      and bone peptide injection under local anesthesia. The deep tissue with the
      tenderness was released in the operation, and the result was evaluated 1 week
      after the surgery to decide whether to conduct another surgery. No more than 3
      treatment sessions were administered. The efficacy was evaluated according to
      nimodipine method by the principles of Chinese clinical drug guidance, and the
      complications of the surgery were observed. RESULTS: Six months after the
      surgery, 28 cases had excellent results, 3 had good outcomes, 2 showed
      improvement, and 2 failed to respond favorably, with a rate of good and excellent
      result of 94.2%. No adverse side effect was recorded in the follow up of the
      patients. CONCLUSION: Water needle knife release combined with bone peptide
      injection can produce a good result in the treatment of heel pain.

PMID- 20813714
TI  - [Therapeutic effect of staged surgery for central cord syndrome of the cervical
      spine].
AB  - OBJECTIVE: To evaluate the effect of staged surgical treatment on central cord
      syndrome of the cervical spine. METHODS: A retrospective analysis was conducted
      in 36 cases of central cord syndrome of the cervical spine treated with staged
      surgery. The patients (aged 50 to 79 years, mean 56.9 years) were divided into
      group A (50 to 64 years old, n=20) and group B (above 65 years old, n=16), and
      each group was further divided into 2 subgroups according to the range of
      decompression in the second stage, namely A1, B1 and A2, B2. ASIA motor score
      (AMS) was analyzed before the first-stage surgery, before the second-stage
      surgery and at the last follow-up after the second-stage surgery. RESULTS: All
      the surgeries were performed successfully. The patients were followed up for 12
      to 32 months (mean 18.4 months) after the second-stage surgery. After the first
      stage surgery, the AMS was 75.8-/+14.6 in group A, 73.2-/+13.1 in group B, 78.5
      /+10.2 in group A1, 76.8-/+9.5 in group A2, 72.2-/+12.6 in group B1 and 77.4
      /+18.3 in group B2. The AMS at the last follow-up was 90.7-/+10.5 in group A,
      89.5-/+12.4 in group B, 91.3-/+13.2 in group A1, 90.7-/+14.8 in group A2, 88.5
      /+11.2 in group B1 and 92.4-/+13.6 in group B2. There was no significant
      difference between groups A and B or between the subgroups A1 and A2 and groups
      B1 and group B2. The AMS was 75.8-/+14.6 after the first-stage surgery and 90.7
      /+10.5 at the last follow-up in group A, significantly higher than those in group
      B (73.2-/+13.1 and 89.5-/+12.4, respectively, P<0.05). CONCLUSION: Staged surgery
      is effective for treatment of central cord syndrome of the cervical spine, and
      the effect of the surgery is not related to the patients' age or the range of
      decompression.

PMID- 20813715
TI  - [Expression of topoisomerase II alpha in human colorectal carcinoma and its
      significance].
AB  - OBJECTIVE: To detect the correlation between the expression of topoisomerase 2
      alpha (TOP2A) and the biological behaviors of human colorectal carcinoma.
      METHODS: Immunohistochemistry and real-time RT-PCR were used to detect the
      expression of TOP2A in colorectal carcinomas and normal mucosa. RESULTS: The
      protein and mRNA expressions of TOP2A in the metastatic lymph nodes were
      significantly higher than those in matched primary lesions and normal tissues
      (P<0.05). No significant difference was found in TOP2A expressions between normal
      mucosa and colorectal carcinomas. The protein and mRNA expressions of TOP2A were
      significantly correlated to the lymph node metastasis and invasion depth
      (P<0.05), but not to the differentiation of the tumor (P>0.05). CONCLUSION: TOP2A
      plays an important role in the invasion and metastasis of the colorectal
      carcinomas, and may serve as a valuable indicator for the diagnosis, treatment
      and the prognostic evaluation of the malignancy.

PMID- 20813716
TI  - Investigating predictors of visiting, using, and revisiting an online health
      communication program: a longitudinal study.
AB  - BACKGROUND: Online health communication has the potential to reach large
      audiences, with the additional advantages that it can be operational at all times
      and that the costs per visitor are low. Furthermore, research shows that Internet
      delivered interventions can be effective in changing health behaviors. However,
      exposure to Internet-delivered health-communication programs is generally low.
      Research investigating predictors of exposure is needed to be able to effectively
      disseminate online interventions. OBJECTIVE: In the present study, the authors
      used a longitudinal design with the aim of identifying demographic,
      psychological, and behavioral predictors of visiting, using, and revisiting an
      online program promoting physical activity in the general population. METHODS: A
      webpage was created providing the public with information about health and
      healthy behavior. The website included a "physical activity check," which
      consisted of a physical activity computer-tailoring expert system where visitors
      could check whether their physical activity levels were in line with
      recommendations. Visitors who consented to participate in the present study (n =
      489) filled in a questionnaire that assessed demographics, mode of recruitment,
      current physical activity levels, and health motivation. Immediately after,
      participants received tailored feedback concerning their current physical
      activity levels and completed a questionnaire assessing affective and cognitive
      user experience, attitude toward being sufficiently physically active, and
      intention to be sufficiently physically active. Three months later, participants
      received an email inviting them once more to check whether their physical
      activity level had changed. RESULTS: Analyses of visiting showed that more women
      (67.5%) than men (32.5%) visited the program. With regard to continued use,
      native Dutch participants (odds ratio [OR] = 2.81, 95% confidence interval [CI] =
      1.16-6.81, P = .02) and participants with a strong motivation to be healthy (OR =
      1.46, CI = 1.03-2.07, P = .03) were most likely to continue usage of the program.
      With regard to revisiting, older participants (OR = 1.04, CI = 1.01-1.06, P =
      .01) and highly educated participants (OR = 4.69, CI = 1.44-15.22, P = .01) were
      more likely to revisit the program after three months. In addition, positive
      affective user experience predicted revisiting (OR = 1.64, CI = 1.12-2.39, P =
      .01). CONCLUSIONS: The results suggest that online interventions could
      specifically target men, young people, immigrant groups, people with a low
      education, and people with a weak health motivation to increase exposure to these
      interventions. Furthermore, eliciting positive feelings in visitors may
      contribute to higher usage rates.

PMID- 20813717
TI  - Exploring virtual worlds for scenario-based repeated team training of
      cardiopulmonary resuscitation in medical students.
AB  - BACKGROUND: Contemporary learning technologies, such as massively multiplayer
      virtual worlds (MMVW), create new means for teaching and training. However,
      knowledge about the effectiveness of such training is incomplete, and there are
      no data regarding how students experience it. Cardiopulmonary resuscitation (CPR)
      is a field within medicine in high demand for new and effective training
      modalities. OBJECTIVE: In addition to finding a feasible way to implement CPR
      training, our aim was to investigate how a serious game setting in a virtual
      world using avatars would influence medical students' subjective experiences as
      well as their retention of knowledge. METHODS: An MMVW was refined and used in a
      study to train 12 medical students in CPR in 3-person teams in a repeated fashion
      6 months apart. An exit questionnaire solicited reflections over their
      experiences. As the subjects trained in 4 CPR scenarios, measurements of self
      efficacy, concentration, and mental strain were made in addition to measuring
      knowledge. Engagement modes and coping strategies were also studied. Parametric
      and nonparametric statistical analyses were carried out according to distribution
      of the data. RESULTS: The majority of the subjects reported that they had enjoyed
      the training, had found it to be suitable, and had learned something new,
      although several asked for more difficult and complex scenarios as well as a
      richer virtual environment. The mean values for knowledge dropped during the 6
      months from 8.0/10 to 6.25/10 (P = .002). Self-efficacy increased from before to
      after each of the two training sessions, from 5.9/7 to 6.5/7 (P = .01) after the
      first and from 6.0/7 to 6.7/7 (P = .03) after the second. The mean perceived
      concentration value increased from 54.2/100 to 66.6/100 (P = .006), and in
      general the mental strain was found to be low to moderate (mean = 2.6/10).
      CONCLUSIONS: Using scenario-based virtual world team training with avatars to
      train medical students in multi-person CPR was feasible and showed promising
      results. Although we found no evidence of stimulated recall of CPR procedures in
      our test-retest study, the subjects were enthusiastic and reported increased
      concentration during the training. We also found that subjects' self-efficacy had
      increased after the training. Despite the need for further studies, these
      findings imply several possible uses of MMVW technology for future emergency
      medical training.

PMID- 20813718
TI  - The 2008 Declaration of Helsinki: some reflections.
AB  - This paper reflects on some amendments to the Declaration of Helsinki in 2008. It
      focuses on former paragraphs 5 (now 6) and 19 (now 17). Paragraph 5 suggested
      that the wellbeing of research participants should take precedence over the
      interests of science and society. Paragraph 6 now proposes that it should take
      precedence over all other interests. Paragraph 19, and the new paragraph 17,
      suggest that research involving the members of a disadvantaged population is only
      justified if the clinical trial is likely to benefit them. In both cases, the
      recommendation is that the interests of the research subjects should prevail over
      the interests of third parties. This paper assesses the plausibility of these
      statements, and in order to do so, considers debates on the moral duty to
      participate in biomedical research. It is argued that, even if seen in the
      context of the Declaration as a whole, the statements contained in these
      paragraphs risk offering a misleading portrait of science and risk eroding some
      of the ethical principles that should form the basis of a satisfactory shared
      life, such as altruism and responsibility for our fellows.

PMID- 20813719
TI  - Translocation of Crohn's disease Escherichia coli across M-cells: contrasting
      effects of soluble plant fibres and emulsifiers.
AB  - BACKGROUND: Crohn's disease is common in developed nations where the typical diet
      is low in fibre and high in processed food. Primary lesions overlie Peyer's
      patches and colonic lymphoid follicles where bacterial invasion through M-cells
      occurs. We have assessed the effect of soluble non-starch polysaccharide (NSP)
      and food emulsifiers on translocation of Escherichia coli across M-cells.
      METHODS: To assess effects of soluble plant fibres and food emulsifiers on
      translocation of mucosa-associated E coli isolates from Crohn's disease patients
      and from non-Crohn's controls, we used M-cell monolayers, generated by co-culture
      of Caco2-cl1 and Raji B cells, and human Peyer's patches mounted in Ussing
      chambers. RESULTS: E coli translocation increased across M-cells compared to
      parent Caco2-cl1 monocultures; 15.8-fold (IQR 6.2-32.0) for Crohn's disease E
      coli (N=8) and 6.7-fold (IQR 3.7-21.0) for control isolates (N=5). Electron
      microscopy confirmed E coli within M-cells. Plantain and broccoli NSP markedly
      reduced E coli translocation across M-cells at 5 mg/ml (range 45.3-82.6%
      inhibition, p<0.01); apple and leek NSP had no significant effect. Polysorbate
      80, 0.01% vol/vol, increased E coli translocation through Caco2-cl1 monolayers 59
      fold (p<0.05) and, at higher concentrations, increased translocation across M
      cells. Similarly, E coli translocation across human Peyer's patches was reduced
      45+/-7% by soluble plantain NSP (5 mg/ml) and increased 2-fold by polysorbate-80
      (0.1% vol/vol). CONCLUSIONS: Translocation of E coli across M-cells is reduced by
      soluble plant fibres, particularly plantain and broccoli, but increased by the
      emulsifier Polysorbate-80. These effects occur at relevant concentrations and may
      contribute to the impact of dietary factors on Crohn's disease pathogenesis.

PMID- 20813720
TI  - Human papillomavirus infection in female sex workers in Lima, Peru.
AB  - OBJECTIVES: To determine the prevalence and risk factors for human papillomavirus
      (HPV) infection in female sex workers (FSW) in Lima, Peru. METHODS: Cross
      sectional study of 87 FSW. Information regarding demographics, sex work
      practices, and genital and blood specimens was collected. RESULTS: Forty-four
      (50.6%) of 87 FSW had HPV detected in cervical swabs. The prevalence of
      coinfection by two or more HPV types was 39.1%. Thirty-one (35.6%) were infected
      by at least one high-risk HPV type, representing 70.5% of women with HPV
      infection. HPV infection was associated with younger age but not with any
      demographic or sexual characteristics. CONCLUSIONS: Our study confirms the high
      prevalence of HPV infection in FSW reported by other groups and suggests that
      brothel-based FSW may be at lower risk for acquiring high-risk HPV infection.

PMID- 20813721
TI  - Taxi driver training in Madagascar: the first step in developing a functioning
      prehospital emergency care system.
AB  - BACKGROUND: Prehospital care in developing countries is severely lacking. Few
      countries can afford the relatively expensive formalised Western model of a
      prehospital emergency medical system. The WHO has highlighted the development of
      layperson first responder programmes as the most basic step in the development of
      a functioning prehospital system. AIM: To describe the first training programme
      of its kind, run in Mahajanga, Madagascar. The faculty was invited by Mahajanga
      Medical School. METHODS AND RESULTS: Local input was taken into account in
      developing the curriculum. 26 taxi drivers were invited to attend in cooperation
      with the local municipality. The faculty consisted of five instructors from the
      Division of Emergency Medicine and EMSSA, plus local doctors from University
      Hospital Mahajanga. The 1-day course included workshops on prehospital scene
      management, bleeding and broken bones, immobilisation and patient movement, and
      labour and delivery. The workshops made use of commonly available items only
      including packets, string and towels; French and Malagasy translators were
      available throughout. CONCLUSIONS: Both faculty and candidates deemed the course
      a success and plans for formal evaluation of knowledge and skill retention are
      underway. Future plans are to continue the training using local instructors and
      in rural districts.

PMID- 20813722
TI  - Unilateral lung whiteout: beyond the standard differential diagnosis.

PMID- 20813723
TI  - Cardiac amyloidosis with giant atria.

PMID- 20813724
TI  - Assessment of aortic stenosis severity: when the gradient does not fit with the
      valve area.

PMID- 20813725
TI  - Silent myocardial infarction: the risk beyond the first admission.

PMID- 20813726
TI  - Coronary revascularisation in the patient with diabetes: balancing risk and
      benefit.

PMID- 20813727
TI  - Inconsistent grading of aortic valve stenosis by current guidelines: haemodynamic
      studies in patients with apparently normal left ventricular function.
AB  - BACKGROUND: On echocardiography approximately one-third of patients with severe
      aortic valve stenosis based on aortic valve area (AVA<1.0 cm(2)) demonstrate a
      non-severe mean pressure gradient (DeltaPm; < or =40 mm Hg) despite apparently
      normal left ventricular function. It has been suggested that inconsistent
      echocardiographic grading may be due to 'paradoxical' low stroke volume. However,
      the correct echocardiographic assessment of stroke volume hinges on the often
      problematic measurement of the left ventricular outflow tract (LVOT) diameter.
      OBJECTIVE: To investigate whether inconsistent grading and reduced stroke volume
      persist when the quantification of aortic valve stenosis is based on cardiac
      catheterisation which is independent of LVOT measurements. METHODS AND RESULTS:
      333 consecutive patients underwent cardiac catheterisation within 30 days after
      their index echocardiography showing an AVA < or =2 cm(2) and shortening fraction
      > or =30%. On invasive testing 85 patients (26%) demonstrated inconsistent (AVA<1
      cm(2) and DeltaPm< or =40 mm Hg) and 153 (46%) consistent grading (AVA<1 cm(2)
      and DeltaPm>40 mm Hg) with the remainder (28%) presenting with a calculated AVA>
      or =1 cm(2). Inconsistently graded patients were older (71 vs 67 years, p<0.006)
      with no differences in sex or body surface area between groups. Stroke volume and
      stroke volume index were significantly lower in inconsistently graded patients
      (63+/-14 vs 73+/-18 ml and 35+/-7 vs 39+/-7 ml/m(2), respectively, both p<0.001).
      However, 41/85 (48%) of inconsistently graded patients had a normal stroke volume
      index >35 ml/m(2). CONCLUSION: In the framework of current guidelines
      inconsistent grading of aortic valve stenosis is common, extends to cardiac
      catheterisation and is only partially explained by low stroke volume despite
      apparently normal left ventricular systolic function.

PMID- 20813728
TI  - Central venous spasm during pacemaker insertion.

PMID- 20813729
TI  - Role of real time three-dimensional transesophageal echocardiography in guidance
      of interventional procedures in cardiology.

PMID- 20813730
TI  - A single catheter across every valve.

PMID- 20813731
TI  - Use of cardiovascular magnetic resonance imaging in the assessment of left
      ventricular function, scar and viability in patients with ischaemic
      cardiomyopathy and chronic myocardial infarction.

PMID- 20813732
TI  - Cardiac pacing in infants and children.

PMID- 20813734
TI  - Multivessel revascularisation in ST-elevation myocardial infarction: too early to
      change the guidelines.

PMID- 20813736
TI  - Long-term dual antiplatelet therapy after percutaneous coronary intervention.

PMID- 20813737
TI  - Pulmonary ossification: an unusual incidental finding of a transthoracic CT
      guided needle biopsy of a lung lesion.

PMID- 20813738
TI  - An outbreak of H1N1 influenza in a respiratory unit.

PMID- 20813739
TI  - Influence of oral N-acetylcysteine on the course of chronic diarrhea in children
      aged between 2 and 36 months.

PMID- 20813740
TI  - Does beta-catenin have a role in pathogenesis of sebaceous cell carcinoma of the
      eyelid?
AB  - AIM: Expression of beta-catenin in sebaceous cell carcinoma (SbCC) of the eyelid
      and its correlation with histopathological features. METHOD: 48 cases of SbCC
      were analysed immunohistochemically using monoclonal beta-catenin antibody and
      the results correlated with tumour size, histopathological differentiation,
      orbital invasion and pagetoid spread. RESULTS: Cytoplasmic overexpression of beta
      catenin was seen in 66% cases of SbCC which correlated positively with tumour
      size, orbital invasion and pagetoid spread. This correlation was found to be
      significant in tumour size > 2 cm (p = 0.242). Nuclear staining was not observed
      in any of the cases. CONCLUSION: Cytoplasmic overexpression of beta-catenin was
      observed in the majority of the cases of SbCC of eyelid, and this correlated
      significantly with tumour size. The authors therefore hypothesise that beta
      catenin overexpression in SbCC of eyelid may be a result of Wnt/beta-catenin
      pathway dysregulation. However, its role both in the development of sebaceous
      cell carcinoma of the eyelid as well as its prognosis needs to be explored
      further.

PMID- 20813741
TI  - Open-angle glaucoma and ocular perfusion.

PMID- 20813742
TI  - Delayed suprachoroidal haemorrhage following Boston Keratoprosthesis in two
      aniridic patients.

PMID- 20813743
TI  - Corneal collagen cross-linking: promises and problems.

PMID- 20813745
TI  - Blindness certification of children 1 year after diagnosis: findings from the
      British Childhood Vision Impairment Study.

PMID- 20813746
TI  - Submacular haemorrhages associated with neovascular age-related macular
      degeneration.
AB  - The exact incidence of submacular haemorrhage (SMH) in patients with neovascular
      age-related macular degeneration (nAMD) is unknown, and risk factors for its
      occurrence ill defined. It is known, however, to be a relatively common problem
      and important because the visual prognosis of these patients is poor.
      Unfortunately, patients with significant SMH were excluded from all the recent
      major randomised control trials for nAMD with antivascular endothelial growth
      factor (VEGF) agents and photodynamic therapy, and as such, the optimum
      management of patients is uncertain. SMH can present initially or during
      treatment of nAMD. The location, size, thickness and duration of SMH have an
      important bearing on treatment and outcomes. Thin or extrafoveal SMH are probably
      best treated with anti-VEGF agents alone. It has been proposed that patients with
      moderate-sized SMH, particularly thick haemorrhages, have an improved prognosis
      with surgical SMH displacement combined with treatment of CNVM if present. SMH
      drainage, macular translocation and RPE patch grafting are reserved for more
      severe extensive cases of SMH. Using these techniques, outcomes better than the
      natural history have been achieved. This review aims to summarise what is known
      about SMH in nAMD and will discuss a variety of therapeutic interventions.

PMID- 20813747
TI  - Juvenile xanthogranuloma with  bilateral optic neuritis.

PMID- 20813748
TI  - Association between primary open-angle glaucoma (POAG) and WDR36 sequence
      variance in Italian families affected by POAG.
AB  - BACKGROUND/AIMS: To assess the involvement of WDR36 sequence variance in primary
      open-angle glaucoma (POAG) in Italian patients. METHODS: A cohort of 34 Italian
      families affected by POAG was analysed by denaturing high-performance liquid
      chromatography for mutation in the WDR36 gene. Among the 34 families enrolled, 25
      were affected by high-tension glaucoma (HTG), four by juvenile open-angle
      glaucoma and one by normal tension glaucoma. In addition, four families presented
      both juvenile open-angle glaucoma and HTG-POAG patients within the same pedigree.
      RESULTS: Four previously identified intronic polymorphisms (IVS5+30C->T; IVS12+90
      G->T; IVS13+89G->A; IVS16-30A->G) and a novel one (IVS21-75G->A) have been
      identified. In addition, one proband was found to carry the p.D658G mutation
      reported as the more recurrent disease-causing allele. CONCLUSIONS: The findings
      suggest that WDR36 sequence variance is only a rare cause of glaucoma in Italian
      families. Clearly, investigation of additional families with extensive studies is
      needed to clarify the role of WDR36 in the pathophysiology of glaucoma.

PMID- 20813750
TI  - Power and consequences: statistical planning in clinical research studies.

PMID- 20813752
TI  - Real-time mapping of the subepithelial nerve plexus by in vivo confocal laser
      scanning microscopy.
AB  - AIM: To produce two-dimensional reconstruction maps of the subepithelial nerve
      plexus (SEP) in living cornea by in vivo laser scanning confocal microscopy in
      real time. METHODS: In vivo confocal laser scanning microscopy (Heidelberg
      Retinal Tomograph II in conjunction with the Rostock Cornea Module) was performed
      on normal eyes (n=6) and eyes after laser-assisted in situ keratomileusis (LASIK)
      (n=4). Source data (frame rate 30 Hz) were used to create large-scale maps of the
      scanned area in Automatic Real Time composite mode. The algorithm aligns single
      live images onto the previously mapped composite image using landmark feature
      based image processing. RESULTS: Real-time mapping of the SEP was performed on a
      large-scale area up to 3.2x3.2 mm (3072x3072 pixels) in healthy subjects and in
      post-LASIK patients. Two-dimensional structures of the SEP were imaged in all 10
      eyes. Mapping quality as well as acquisition time were dependent on subject
      compliance and examiner experience. CONCLUSION: The described method permits real
      time in vivo mapping of the SEP, thus providing the necessary basis for
      statistically robust conclusions concerning morphometric plexus alterations.

PMID- 20813751
TI  - The quality of pharmacoeconomic evaluations of age-related macular degeneration
      therapeutics: a systematic review and quantitative appraisal of the evidence.
AB  - AIM: To appraise the quality of published pharmacoeconomic studies of therapeutic
      interventions for age-related macular degeneration (AMD). METHODS: Systematic
      review of the literature and evaluation of study quality using the Quality of
      Health Economic Studies instrument. A systematic search of the English-language
      literature for economic studies of therapeutic interventions for AMD from 1990 to
      March 2008 was performed. RESULTS: A total of 3637 articles were initially
      identified. Only 24 met eligibility criteria and were rated using the Quality of
      Health Economic Studies. The mean quality overall rating was 61.6, with quality
      scores ranging from 18 to 92. There was a higher mean quality score in the
      studies designed as clinical trials versus observational type designed studies
      (mean=74.7(11.4), 52.6 (16.5) respectively, p=0.002) and studies in which the
      statistical analyses were clearly presented versus studies in which the
      statistical analyses were not so clear (mean=74.3 (12.3), 53.1 (16.1)
      respectively, p=0.004). Interestingly, government funded studies exhibited a
      similar mean quality score to studies that were funded by industry (mean=71.0
      (15.1), 61.7 (18.5) respectively, p=0.25). A general linear model was fitted
      using those independent variables which were significantly associated with
      quality score. The variables 'study design' and 'statistics presented clearly'
      were found to be jointly significant and explained nearly 70% of the variation in
      the dependent variable (R(2)=0.68). CONCLUSIONS: Our analysis reveals that the
      methodological quality of the health economic analysis of AMD therapeutic
      interventions in the literature is suboptimal. There is considerable variation in
      methodological rigour between the articles, and we have identified several
      attributes that are predictive of study quality.

PMID- 20813754
TI  - External dacryocystorhinostomy with and without silicone intubation.

PMID- 20813755
TI  - Is age a risk factor for diabetic retinopathy?

PMID- 20813756
TI  - PPARalpha-dependent activation of cell cycle control and DNA repair genes in
      hepatic nonparenchymal cells.
AB  - Peroxisome proliferator-activated receptor-alpha (PPARalpha) mediates the diverse
      biological effects of peroxisome proliferator (PP) chemicals, including fatty
      acid catabolism, hepatomegaly, hepatocyte proliferation, and hepatocarcinogenesis
      in rodents. However, transgenic mice expressing a constitutively active PPARalpha
      in hepatocytes (VP16PPARalpha) do not develop hepatocellular carcinomas in spite
      of hepatocyte proliferation and hepatomegaly; this suggests that activation of
      genes in nonparenchymal cells may have a critical role in PP-induced
      carcinogenesis. VP16PPARalpha mice exhibited massive peroxisome proliferation and
      hepatomegaly as well as increased mortality upon Wy-14,643 treatment. Several
      genes involved in cell cycle or DNA damage repair, such as Chek1, Prkdc, Mcm, and
      Rad51, were significantly induced to a similar extent between wild-type and
      VP16PPARalpha mice after Wy-14,643 administration. This induction was completely
      abolished in Pparalpha-null mice, suggesting a PPARalpha-dependent pathway. These
      data revealed a DNA damage response signaling network as an early event upon PP
      treatment and provide novel putative mechanisms for PP-induced hepatocellular
      carcinoma.

PMID- 20813757
TI  - Chemical discrimination between dC and 5MedC via their hydroxylamine adducts.
AB  - The presence of the methylated nucleobase (5Me)dC in CpG islands is a key factor
      that determines gene silencing. False methylation patterns are responsible for
      deteriorated cellular development and are a hallmark of many cancers. Today genes
      can be sequenced for the content of (5Me)dC only with the help of the bisulfite
      reagent, which is based exclusively on chemical reactivity differences
      established by the additional methyl group. Despite intensive optimization of the
      bisulfite protocol, the method still has specificity problems. Most importantly
      ~95% of the DNA analyte is degraded during the analysis procedure. We discovered
      that the reagent O-allylhydroxylamine is able to discriminate between dC and
      (5Me)dC. The reagent, in contrast to bisulfite, does not exploit reactivity
      differences but gives directly different reaction products. The reagent forms a
      stable mutagenic adduct with dC, which can exist in two states (E versus Z). In
      case of dC the allylhydroxylamine adduct switches into the E-isomeric form, which
      generates dC to dT transition mutations that can easily be detected by
      established methods. Significantly, the (5Me)dC-adduct adopts exclusively the Z
      isomeric form, which causes the polymerase to stop. O-allylhydroxylamine does
      allow differentiation between dC and (5Me)dC with high accuracy, leading towards
      a novel and mild chemistry for methylation analysis.

PMID- 20813758
TI  - M-ORBIS: mapping of molecular binding sites and surfaces.
AB  - M-ORBIS is a Molecular Cartography approach that performs integrative high
      throughput analysis of structural data to localize all types of binding sites and
      associated partners by homology and to characterize their properties and
      behaviors in a systemic way. The robustness of our binding site inferences was
      compared to four curated datasets corresponding to protein heterodimers and
      homodimers and protein-DNA/RNA assemblies. The Molecular Cartographies of
      structurally well-detailed proteins shows that 44% of their surfaces interact
      with non-solvent partners. Residue contact frequencies with water suggest that
      ~86% of their surfaces are transiently solvated, whereas only 15% are
      specifically solvated. Our analysis also reveals the existence of two major
      binding site families: specific binding sites which can only bind one type of
      molecule (protein, DNA, RNA, etc.) and polyvalent binding sites that can bind
      several distinct types of molecule. Specific homodimer binding sites are for
      instance nearly twice as hydrophobic than previously described and more closely
      resemble the protein core, while polyvalent binding sites able to form homo and
      heterodimers more closely resemble the surfaces involved in crystal packing.
      Similarly, the regions able to bind DNA and to alternatively form homodimers, are
      more hydrophobic and less polar than previously described DNA binding sites.

PMID- 20813759
TI  - The splicing-factor related protein SFPQ/PSF interacts with RAD51D and is
      necessary for homology-directed repair and sister chromatid cohesion.
AB  - DNA double-stranded breaks (DSBs) are among the most severe forms of DNA damage
      and responsible for chromosomal translocations that may lead to gene fusions. The
      RAD51 family plays an integral role in preserving genome stability by homology
      directed repair of DSBs. From a proteomics screen, we recently identified
      SFPQ/PSF as an interacting partner with the RAD51 paralogs, RAD51D, RAD51C and
      XRCC2. Initially discovered as a potential RNA splicing factor, SFPQ was later
      shown to have homologous recombination and non-homologous end joining related
      activities and also to bind and modulate the function of RAD51. Here, we
      demonstrate that SFPQ interacts directly with RAD51D and that deficiency of both
      proteins confers a severe loss of cell viability, indicating a synthetic lethal
      relationship. Surprisingly, deficiency of SFPQ alone also leads to sister
      chromatid cohesion defects and chromosome instability. In addition, SFPQ was
      demonstrated to mediate homology directed DNA repair and DNA damage response
      resulting from DNA crosslinking agents, alkylating agents and camptothecin. Taken
      together, these data indicate that SFPQ association with the RAD51 protein
      complex is essential for homologous recombination repair of DNA damage and
      maintaining genome integrity.

PMID- 20813760
TI  - An insulator embedded in the chicken alpha-globin locus regulates chromatin
      domain configuration and differential gene expression.
AB  - Genome organization into transcriptionally active domains denotes one of the
      first levels of gene expression regulation. Although the chromatin domain concept
      is generally accepted, only little is known on how domain organization impacts
      the regulation of differential gene expression. Insulators might hold answers to
      address this issue as they delimit and organize chromatin domains. We have
      previously identified a CTCF-dependent insulator with enhancer-blocking activity
      embedded in the 5' non-coding region of the chicken alpha-globin domain. Here, we
      demonstrate that this element, called the alphaEHS-1.4 insulator, protects a
      transgene against chromosomal position effects in stably transfected cell lines
      and transgenic mice. We found that this insulator can create a regulated
      chromatin environment that coincides with the onset of adult alpha-globin gene
      expression. Furthermore, such activity is in part dependent on the in vivo
      regulated occupancy of CTCF at the alphaEHS-1.4 element. Insulator function is
      also regulated by CTCF poly(ADP-ribosyl)ation. Our results suggest that the
      alphaEHS-1.4 insulator contributes in organizing the chromatin structure of the
      alpha-globin gene domain and prevents activation of adult alpha-globin gene
      expression at the erythroblast stage via CTCF.

PMID- 20813761
TI  - Substance abuse treatment counselors and tobacco use: a comparison of
      comprehensive and indoor-only workplace smoking bans.
AB  - INTRODUCTION: While indoor smoking bans reduce employee tobacco use, less is
      known about whether comprehensive bans, which prohibit smoking in both indoor and
      outdoor areas, are associated with lower rates of tobacco use than indoor-only
      bans. METHODS: This study integrated data collected via mailed surveys from 1,910
      substance abuse treatment counselors and telephone interviews with 417
      administrators of substance abuse treatment organizations. Multinomial logistic
      regression was used to estimate the associations between counselors' self
      reported tobacco use and administrators' reports about organizational smoking
      bans while controlling for counselors' professional and demographic
      characteristics. RESULTS: In this sample, 20.3% of counselors were current
      tobacco users, 47.7% identified as former users, and 32.0% reported never using
      tobacco products. Only 19.5% of counselors worked in a treatment organization
      that had a comprehensive smoking ban. The likelihood of being a current tobacco
      user, compared with being a former user or nonuser, was significantly lower for
      counselors in organizations with comprehensive bans even after controlling for
      professional and demographic characteristics. CONCLUSIONS: Although relatively
      few substance abuse counselors worked in treatment organizations with
      comprehensive bans, such bans may represent a promising direction for tobacco
      control. Given recent research documenting how tobacco use is negatively
      associated with the delivery of smoking cessation services by health care
      workers, additional research on the impact of comprehensive environmental tobacco
      policies is needed.

PMID- 20813763
TI  - Municipal solid waste management in Phnom Penh, capital city of Cambodia.
AB  - This paper presents an overview of municipal solid waste management (MSWM) for
      both technical and regulatory arrangements in the municipality of Phnom Penh
      (MPP), Cambodia. Problems with the current MSWM are identified, and challenges
      and recommendations for future improvement are also given in this paper. MPP is a
      small city with a total area of approximately 374 km(2) and an urban population
      of about 1.3 million in 2008. For the last 14 years, average annual municipal
      solid waste (MSW) generated in MPP has increased rapidly from 0.136 million tons
      in 1995 to 0.361 million tons in 2008. The gross generation rate of MSW per
      capita was 0.74 kg day(-1). However, the per capita household waste generation
      was 0.487 kg day(- 1). At 63.3%, food waste is the predominant portion of
      generated waste, followed by plastics (15.5%), grass and wood (6.8%), and paper
      and cardboard (6.4%). The remaining waste, including metals, glass,
      rubber/leather, textiles, and ceramic/ stone, accounted for less than 3%. Waste
      recycling through informal sectors is very active; recycled waste accounted for
      about 9.3% of all waste generated in 2003. Currently, the overall technical
      arrangement, including storage and discharge, collection and transport, and
      disposal, is still in poor condition, which leads to environmental and health
      risks. These problems should be solved by improving legislation, environmental
      education, solid waste management facilities, and management of the waste
      scavengers.

PMID- 20813762
TI  - British Association for Psychopharmacology consensus statement on evidence-based
      treatment of insomnia, parasomnias and circadian rhythm disorders.
AB  - Sleep disorders are common in the general population and even more so in clinical
      practice, yet are relatively poorly understood by doctors and other health care
      practitioners. These British Association for Psychopharmacology guidelines are
      designed to address this problem by providing an accessible up-to-date and
      evidence-based outline of the major issues, especially those relating to reliable
      diagnosis and appropriate treatment. A consensus meeting was held in London in
      May 2009. Those invited to attend included BAP members, representative clinicians
      with a strong interest in sleep disorders and recognized experts and advocates in
      the field, including a representative from mainland Europe and the USA.
      Presenters were asked to provide a review of the literature and identification of
      the standard of evidence in their area, with an emphasis on meta-analyses,
      systematic reviews and randomized controlled trials where available, plus updates
      on current clinical practice. Each presentation was followed by discussion, aimed
      to reach consensus where the evidence and/or clinical experience was considered
      adequate or otherwise to flag the area as a direction for future research. A
      draft of the proceedings was then circulated to all participants for comment. Key
      subsequent publications were added by the writer and speakers at draft stage. All
      comments were incorporated as far as possible in the final document, which
      represents the views of all participants although the authors take final
      responsibility for the document.

PMID- 20813764
TI  - Risk assessment applied to air emissions from a medium-sized Italian MSW
      incinerator.
AB  - Risk assessment is a well established procedure for the analysis of the adverse
      impacts of pollutant substances emitted by waste treatment plants. The aim of the
      present study was the determination of the impact on human health associated with
      the activities of an incinerator in the Emilia-Romagna region (Northern Italy).
      The dispersion of heavy metals and organic pollutants monitored at plant stacks
      was predicted by the Gaussian model ISC3 (US-EPA). This analysis led to the
      estimation of risk, connected with various pollutants showing toxic and
      carcinogenic activities, for different receptors. The values obtained were first
      compared with the acceptability limits set by US-EPA, and then graphically
      represented as a territorial dispersion. A cautious approach was followed to
      calculate risk, by considering the worst, albeit realistic and reliable, estimate
      for the different parameters. The calculated exposure pathways resulted in
      different contributions depending on the receptor category (children and adults),
      even if direct exposure (via inhalation) is generally predominant. However, the
      resulting risk for both single pollutants studied and their combination all
      together proved to be within the acceptable limits (all lifetime individual risks
      being below 10(-6)), according to the procedure followed. The obtained results
      highlight the importance of using reliable monitoring data on the studied
      contamination source and, in particular, suggest the advisability of a more in
      depth study on the pollution from incineration stacks.

PMID- 20813765
TI  - Removal of uraemic retention solutes in standard bicarbonate haemodialysis and
      long-hour slow-flow bicarbonate haemodialysis.
AB  - BACKGROUND: Several studies already stressed the importance of haemodialysis (HD)
      time in the removal of uraemic toxins. In those studies, however, also the amount
      of dialysate and/or processed blood was altered. The present study aimed to
      investigate the isolated effect of the factor time t (by processing the same
      total blood and dialysate volume in two different time schedules) on the removal
      and kinetic behaviour of some small, middle and protein-bound molecules. METHODS:
      The present study had a crossover design: 11 stable anuric HD patients underwent
      two bicarbonate HD sessions (~ 4 and ~ 8 h) in a random sequence, at least 1 week
      apart. The GENIUS single-pass batch dialysis system and the high-flux FX80
      dialysers (Fresenius Medical Care, Bad Homburg, Germany) were used. The volume of
      blood and dialysate processed, volume of ultrafiltration, and dialysate
      composition were prescribed to be the same. For each patient, blood was sampled
      from the arterial line at 0, 60, 120, 180 and 240 min (all sessions), and at 360
      and 480 min (8-h sessions). Dialysate was sampled at the end of HD from the
      dialysate tank. The following solutes were investigated: (i) small molecules:
      urea, creatinine, phosphorus and uric acid; (ii) middle molecule: beta(2)M; and
      (iii) protein-bound molecules: homocysteine, hippuric acid, indole-3-acetic acid
      and indoxyl sulphate. Total solute removals (solute concentration in the spent
      dialysate of each analyte * 90 L - the volume of dialysate) (TSR), clearances
      (TSR of a solute/area under the plasma water concentration time curve of the
      solute) (K), total cleared volumes (K * dialysis time) (TCV), and dialyser
      extraction ratios (K/blood flow rate) (ER) were determined. The percent
      differences of TSR, K, TCV and ER between 4- and 8-h dialyses were calculated.
      Single-pool Kt/Vurea, and post-dialysis percent rebounds of urea, creatinine and
      beta(2)M were computed. RESULTS: TSR, TCV and ER were statistically significantly
      larger during prolonged HD for all small and middle molecules (at least, P <
      0.01). Specifically, the percent increases of TSR (8 h vs 4 h) were: for urea
      22.6.0% (P < 0.003), for creatinine 24.8% (P < 0.002), for phosphorus 26.6% (P <
      0.001), and for beta(2)M 39.2% (P < 0.005). No statistically significant
      difference was observed for protein-bound solutes in any of the parameters being
      studied. Single-pool Kt/Vurea was 1.41 +/- 0.19 for the 4-h dialysis sessions and
      1.80 +/- 0.29 for the 8-h ones. The difference was statistically significant (P <
      0.0001). Post-dialysis percent rebounds of urea, creatinine and beta(2)M were
      statistically significantly greater in the 4-h dialysis sessions (at least, P <
      0.0002). CONCLUSIONS: The present controlled study using a crossover design
      indicates that small and middle molecules are removed more adequately from the
      deeper compartments when performing a prolonged HD, even if blood and dialysate
      volumes are kept constant. Hence, factor time t is very important for these
      retention solutes. The kinetic behaviour of protein-bound solutes is completely
      different from that of small and middle molecules, mainly because of the strength
      of their protein binding.

PMID- 20813766
TI  - Lipids and renal cystic disease.

PMID- 20813767
TI  - Serum fibroblast growth factor-23 (FGF-23) levels are independently associated
      with left ventricular mass and myocardial performance index in maintenance
      haemodialysis patients.
AB  - BACKGROUND: Fibroblast growth factor-23 (FGF-23) is a phosphorus-regulating
      substance. Circulating FGF-23 levels increase markedly in dialysis patients and
      are independently associated with increased risk of mortality. Given the fact
      that cardiovascular disease is the leading cause of death in dialysis patients,
      the aim of this study was to test if elevated FGF-23 levels might be associated
      with left ventricular mass index (LVMI) and left ventricular index of myocardial
      performance (MPI) in maintenance haemodialysis patients. METHODS: In this cross
      sectional study, plasma FGF-23 concentrations were measured using a C-terminal
      human enzyme-linked immunosorbent assay kit, and echocardiography was performed
      in 128 maintenance haemodialysis patients (65 women and 63 men, mean age: 55.5 +/
      13 years, mean haemodialysis vintage: 52 +/- 10 months, all patients are on
      haemodialysis thrice a week) and 40 control subjects (21 women and 19 men; mean
      age: 54 +/- 11 years) with normal kidney function (eGFR > 90 mL/min/1.73 m(2)).
      RESULTS: Serum FGF-23 levels were elevated when compared with age- and gender
      matched controls with preserved kidney function [(median 958 RU/mL; interquartile
      range 106-1894 RU/mL) vs (median 27 RU/mL; interquartile range 11-35), P <
      0.0001]. Patients with a history of coronary artery disease and aortic valve
      calcifications had higher levels of log FGF-23 than those without (3.00 +/- 0.22
      vs 2.82 +/- 0.26, P = 0.002; and 3.06 +/- 0.19 vs 2.83 +/- 0.26, P = 0.0001,
      respectively). Patients with MPI > 0.47 had higher serum FGF-23 levels than those
      with MPI < 0.47 [(median 1156 RU/mL; interquartile range 396-1894 RU/mL) vs
      (median 657 RU/mL; interquartile range 106-1102 RU/mL), P = 0.0001]. Significant
      correlations were recorded between log FGF-23 levels and LVMI (r = 0.281, P =
      0,007) and MPI (r = 0.555, P = 0.0001). Multivariable-adjusted regression
      analyses revealed that increased log FGF-23 concentrations were independently
      associated with increased left ventricular mass index (30% increase per 1-SD
      increase in log FGF-23 concentration, P = 0.002) and increased MPI (28.5%
      increase per 1-SD increase in log FGF-23 concentration, P = 0.001). CONCLUSIONS:
      Plasma FGF-23 concentration is independently associated with LVMI and MPI in
      maintenance haemodialysis patients. Further prospective studies are needed to
      clarify whether increased serum FGF-23 level is a marker or a potential mechanism
      for left ventricular involvement in patients with end-stage renal disease.

PMID- 20813768
TI  - National survey of the current provision of specialist palliative care services
      for patients with end-stage renal disease.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) experience a significant
      symptom burden and have complex needs. However, involvement of specialist
      palliative care (SPC) services with these patients has previously been shown to
      be limited. This study assesses the current provision of and access to SPC
      services for ESRD patients in the UK and considers how the provision has evolved
      over recent years. METHODS: A questionnaire was sent to the lead clinician for
      all UK adult hospital, hospice and community SPC services, identified from the
      Hospice and Palliative Care Directory 2008. Non-responders were mailed again
      after 5 weeks. Descriptive statistics and qualitative thematic analysis were
      performed. RESULTS: Three hundred and eighteen of 611 (52%) questionnaires were
      returned. Ninety-six per cent stated that SPC services have a role in caring for
      patients with ESRD. Two hundred and eighty-one of 318 (88%) accepted referrals,
      and 185 of 281 (66%) reported that 'none or few were referred'. Only 7% and 17%
      of respondents used specific ESRD referral and treatment guidelines,
      respectively; whereas 79% used the Liverpool Care Pathway for the Dying Patient.
      Seven per cent undertook joint renal and SPC multi-disciplinary team (MDT)
      meetings, and 3% held joint out-patient clinics. Forty percent of respondents
      proposed initiatives to improve palliative care for ESRD patients, with mutual
      education and collaborative working being key themes for improvement.
      CONCLUSIONS: The majority of SPC services accept ESRD patients, but limited
      numbers are referred. Respondents indicated that this barrier could be addressed
      by closer collaboration and better communication and education between renal and
      SPC services. Other initiatives to enable delivery of SPC to increased numbers of
      ESRD patients include the use of specific referral and clinical care guidelines
      and expansion of joint MDT meetings and out-patient clinics.

PMID- 20813769
TI  - Endothelin type A and B receptors in the control of afferent and efferent
      arterioles in mice.
AB  - BACKGROUND: Endothelin 1 contributes to renal blood flow control and pathogenesis
      of kidney diseases. The differential effects, however, of endothelin 1 (ET-1) on
      afferent (AA) and efferent arterioles (EA) remain to be established. METHODS: We
      investigated endothelin type A and B receptor (ETA-R, ETB-R) functions in the
      control of AA and EA. Arterioles of ETB-R deficient, rescued mice [ETB(-/-)] and
      wild types [ETB(+/+)] were microperfused. RESULTS: ET-1 constricted AA stronger
      than EA in ETB(-/-) and ETB(+/+) mice. Results in AA: ET-1 induced similar
      constrictions in ETB(-/-) and ETB(+/+) mice. BQ-123 (ETA-R antagonist) inhibited
      this response in both groups. ALA-ET-1 and IRL1620 (ETB-R agonists) had no effect
      on arteriolar diameter. L-NAME did neither affect basal diameters nor ET-1
      responses. Results in EA: ET-1 constricted EA stronger in ETB(+/+) compared to
      ETB(-/-). BQ-123 inhibited the constriction completely only in ETB(-/-). ALA-ET-1
      and IRL1620 constricted only arterioles of ETB(+/+) mice. L-NAME decreased basal
      diameter in ETB(+/+), but not in ETB(-/-) mice and increased the ET-1 response
      similarly in both groups. The L-NAME actions indicate a contribution of ETB-R in
      basal nitric oxide (NO) release in EA and suggest dilatory action of ETA-R in EA.
      CONCLUSIONS: ETA-R mediates vasoconstriction in AA and contributes to
      vasoconstriction in EA in this mouse model. ETB-R has no effect in AA but
      mediates basal NO release and constriction in EA. The stronger effect of ET-1 on
      AA supports observations of decreased glomerular filtration rate to ET-1 and
      indicates a potential contribution of ET-1 to the pathogenesis of kidney
      diseases.

PMID- 20813771
TI  - CABG in CKD: untangling the letters of risk.

PMID- 20813770
TI  - Angiotensin II blockade upregulates the expression of Klotho, the anti-ageing
      gene, in an experimental model of chronic cyclosporine nephropathy.
AB  - BACKGROUND: The Klotho gene plays a role in suppressing ageing-related disorders.
      It is suggested that activation of renin-angiotensin system (RAS) or oxidative
      stress suppresses Klotho in the kidney. This study evaluated the association
      between Klotho expression and RAS in cyclosporine (CsA)-induced renal injury.
      METHODS: Chronic CsA nephropathy was induced by administering CsA (30 mg/kg) to
      mice on a low-salt diet (LSD) for 4 weeks. A normal-salt diet (NSD) was used as
      the control. Reverse transcription-polymerase chain reaction, western blot and
      immunohistochemistry were performed for Klotho and intrarenal RAS activity was
      measured using immunohistochemistry for angiotensinogen and renin. Oxidative
      stress was measured with urinary excretion of 8-hydroxy-2'-deoxyguanosine (8
      OHdG). RESULTS: CsA treatment decreased Klotho mRNA and protein in mouse kidney
      in a dose-dependent and time-dependent manner, but a concurrent treatment with
      losartan, an angiotensin II type 1 (AT1) receptor blocker, reversed the decrease
      in Klotho expression with histological improvement. This finding was more marked
      in the LSD than the NSD. Klotho expression was correlated with angiotensinogen
      and renin expression, tubulointerstitial fibrosis score and urinary 8-OHdG
      excretion. CONCLUSIONS: Angiotensin II may play a pivotal role in regulating
      Klotho expression in CsA-induced renal injury. AT1 receptor blocker may inhibit
      the ageing process by decreasing oxidative stress caused by CsA.

PMID- 20813772
TI  - Altered M1/M2 activation patterns of monocytes in severe relapsing experimental
      rat model of multiple sclerosis. Amelioration of clinical status by M2 activated
      monocyte administration.
AB  - OBJECTIVES: We investigated proinflammatory M1 and immunomodulatory M2 activation
      profiles of circulating monocytes in relapsing experimental autoimmune
      encephalomyelitis (EAE) model of multiple sclerosis, and tested whether altered
      M1/M2 equilibrium promotes CNS inflammation. RESULTS: Approaches of MRI
      macrophage tracking with USPIO nanoparticles and expression patterns of M1/M2
      macrophages and microglia in brain and M1/M2 monocytes in blood samples at
      various disease stages revealed that M1/M2 equilibrium in blood and CNS favors
      mild EAE, while imbalance towards M1 promotes relapsing EAE. We consequently
      investigated whether M2 activated monocyte restoration in peripheral blood could
      cure acute clinical EAE disease. Administration of ex vivo activated M2 monocytes
      both suppressed ongoing severe EAE and increased immunomodulatory expression
      pattern in lesions, confirming their role in the induction of recovery.
      CONCLUSION: We conclude that imbalance of monocyte activation profiles and
      impaired M2 expression, are key factors in development of relapses. Our study
      opens new perspectives for therapeutic applications in MS.

PMID- 20813773
TI  - Validity of an Internet version of the Multiple Sclerosis Neuropsychological
      Questionnaire.
AB  - BACKGROUND: Neuropsychological batteries are long and require expertise to
      administer. For this reason, the Multiple Sclerosis Neuropsychological
      Questionnaire (MSNQ) was developed as it is quick and easy to complete. The
      informant version of the scale has proven to be a useful screen for cognitive
      impairment in multiple sclerosis (MS). OBJECTIVE: The objective was to validate
      an Internet version of the MSNQ. METHODS: The following psychometric data were
      collected at home over the Internet in 82 MS patients: (a) patient self-report
      version MSNQ (P-MSNQ), (b) informant version MSNQ (I-MSNQ), and (c) Center for
      Epidemiological Studies Depression Scale (CES-D). Thereafter patients underwent
      in-office testing with the Brief Repeatable Battery of Neuropsychological Tests
      (BRB-N). The sensitivity and specificity of the Internet MSNQ to detect cognitive
      impairment relative to the BRB-N was determined using receiver operating
      characteristic (ROC) curve analysis. RESULTS: Thirty-five percent of the sample
      was cognitively impaired. The P-MSNQ was correlated with depression and two tests
      of the BRB-N. The I-MSNQ was correlated with depression and all five tests of the
      BRB-N. A cut-off score of 26 on the I-MSNQ gave a sensitivity and specificity of
      72% and 60% respectively. Test-retest and internal reliability analyses were
      strong for both the P-MSNQ and I-MSNQ. CONCLUSION: This is the first attempt at
      an Internet validation of the MSNQ. The modest sensitivity and specificity values
      suggest that further research is needed before either the patient or informant
      version of the MSNQ can be used for neuropsychological screening purposes over
      the Internet.

PMID- 20813774
TI  - MS prevalence in New Zealand, an ethnically and latitudinally diverse country.
AB  - BACKGROUND: The prevalence of multiple sclerosis (MS) is not uniform, with a
      latitudinal gradient of prevalence present in most studies. Understanding the
      drivers of this gradient may allow a better understanding of the environmental
      factors involved in MS pathogenesis. METHOD: The New Zealand national MS
      prevalence study (NZMSPS) is a cross-sectional study of people with definite MS
      (DMS) (McDonald criteria 2005) resident in New Zealand on census night, 7 March
      2006, utilizing multiple sources of notification. Capture-recapture analysis
      (CRA) was used to estimate missing cases. RESULTS: Of 2917 people with DMS
      identified, the crude prevalence was 72.4 per 100,000 population, and 73.1 per
      100,000 when age-standardized to the European population. CRA estimated that
      96.7% of cases were identified. A latitudinal gradient was seen with MS
      prevalence increasing three-fold from the North (35 degrees S) to the South (48
      degrees S). The gradient was non-uniform; females with relapsing
      remitting/secondary-progressive (RRMS/SPMS) disease have a gradient 11 times
      greater than males with primary-progressive MS (p < 1 * 10(-7)). DMS was
      significantly less common among those of Maori ethnicity. CONCLUSIONS: This study
      confirms the presence of a robust latitudinal gradient of MS prevalence in New
      Zealand. This gradient is largely driven by European females with the RRMS/SPMS
      phenotype. These results indicate that the environmental factors that underlie
      the latitudinal gradient act differentially by gender, ethnicity and MS
      phenotype. A better understanding of these factors may allow more targeted MS
      therapies aimed at modifiable environmental triggers at the population level.

PMID- 20813776
TI  - Quality control of experimental autoimmune encephalomyelitis.

PMID- 20813777
TI  - Lessons learned from long-term multiple sclerosis treatment trials.

PMID- 20813775
TI  - Development and validation of a patient self-assessed questionnaire on
      satisfaction with communication of the multiple sclerosis diagnosis.
AB  - BACKGROUND: We describe the development and clinical validation of a patient self
      administered tool assessing the quality of multiple sclerosis diagnosis
      disclosure. METHOD: A multiple sclerosis expert panel generated questionnaire
      items from the Doctor's Interpersonal Skills Questionnaire, literature review,
      and interviews with neurology inpatients. The resulting 19-item Comunicazione
      medico-paziente nella Sclerosi Multipla (COSM) was pilot tested/debriefed on
      seven patients with multiple sclerosis and administered to 80 patients newly
      diagnosed with multiple sclerosis. The resulting revised 20-item version (COSM-R)
      was debriefed on five patients with multiple sclerosis, field tested/debriefed on
      multiple sclerosis patients, and field tested on 105 patients newly diagnosed
      with multiple sclerosis participating in a clinical trial on an information aid.
      The hypothesized monofactorial structure of COSM-R section 2 was tested on the
      latter two groups. RESULTS: The questionnaire was well accepted. Scaling
      assumptions were satisfactory in terms of score distributions, item-total
      correlations and internal consistency. Factor analysis confirmed section 2's
      monofactorial structure, which was also test-retest reliable (intraclass
      correlation coefficient [ICC] 0.73; 95% CI 0.54-0.85). Section 1 had only fair
      test-retest reliability (ICC 0.45; 95% CI 0.12-0.69), and three items had 8-21%
      missed responses. CONCLUSIONS: COSM-R is a brief, easy-to-interpret MS-specific
      questionnaire for use as a health care indicator.

PMID- 20813778
TI  - Composite MRI scores improve correlation with EDSS in multiple sclerosis.
AB  - BACKGROUND: Quantitative measures derived from magnetic resonance imaging (MRI)
      have been widely investigated as non-invasive biomarkers in multiple sclerosis
      (MS). However, the correlation of single measures with Expanded Disability Status
      Scale (EDSS) is poor, especially for studies with large population samples.
      OBJECTIVE: To explore the correlation of MRI-derived measures with EDSS through
      composite MRI scores. METHODS: Magnetic resonance images of 126 patients with
      relapsing-remitting MS were segmented into white and gray matter, cerebrospinal
      fluid, T2-hyperintense lesions, gadolinium contrast-enhancing lesions, T1
      hypointense lesions ('black holes': BH). The volumes and average T2 values for
      each of these tissues and lesions were calculated and converted to a z-score (in
      units of standard deviation from the mean). These z-scores were combined to
      construct composite z-scores, and evaluated against individual z-scores for
      correlation with EDSS. RESULTS: Composite scores including relaxation times of
      different tissues and/or volumetric measures generally correlated more strongly
      with EDSS than individual measures. The maximum observed correlation of a
      composite with EDSS was r = 0.344 (p < 0.0001), which is an improvement over the
      highest-performing single MRI measure (BH; r = 0.298, p < 0.001). CONCLUSION: Z
      transformation permits construction of composite scores including volumetric and
      T2-relaxation measures. Inclusion of multiple MRI measures in the composite can
      provide a broader characterization of the disease process, resulting in more
      robust correlations with EDSS.

PMID- 20813780
TI  - "Airplane headache" or flight-related headache?

PMID- 20813779
TI  - Post-traumatic stress disorder, drug abuse and migraine: new findings from the
      National Comorbidity Survey Replication (NCS-R).
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) has been shown to be associated
      with migraine and drug abuse. METHODS: This was an analysis of data from the
      National Comorbidity Survey Replication (NCS-R) to evaluate the association of
      PTSD in those with episodic migraine (EM) and chronic daily headache (CDH).
      RESULTS: Our sample consisted of 5,692 participants. Lifetime and 12-month
      prevalence rates of PTSD were increased in those with EM and CDH. After
      adjustments, the lifetime odds ratio (OR) of PTSD was greater in those with EM
      (OR 3.07 confidence interval [CI]: 2.12, 4.46) compared to those without
      headache; was greater in men than women with EM (men: OR 6.86; CI: 3.11, 15.11;
      women: OR 2.77; CI: 1.83, 4.21); and was comparable or greater than the
      association between migraine with depression or anxiety. The lifetime OR of PTSD
      was also increased in CDH sufferers. The OR of illicit drug abuse was not
      increased in those with EM or CDH unless co-occurring with PTSD or depression.
      CONCLUSION: The lifetime and 12-month OR of PTSD is increased in those with
      migraine or CDH, and is greater in men than women with migraine. The lifetime and
      12-month OR of illicit drug abuse is not increased in those with migraine or CDH
      unless co-occurring with PTSD or depression.

PMID- 20813781
TI  - Association of a Notch 3 gene polymorphism with migraine susceptibility.
AB  - INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts
      and leucoencephalopathy (CADASIL) shares common symptoms with migraine. Most
      CADASIL causative mutations occur in exons 3 and 4 of the Notch 3 gene. This
      study investigated the role of C381T (rs 3815188) and G684A (rs 1043994) single
      nucleotide polymorphisms (SNP) in exons 3 and 4, respectively, of the Notch 3
      gene in migraine. RESULTS: The first part of the study, in a population of 275
      migraineurs and 275 control individuals, found a significant association between
      the C381T variant and migraine, specifically in migraine without aura (MO)
      sufferers. The G684A variant was also found to be significantly associated with
      migraine, specifically in migraine with aura (MA) sufferers. A follow-up study in
      300 migraineurs and 300 control individuals did not show replicated association
      of the C381T variant with migraineurs. However, the G684A variant was again shown
      to be significantly associated with migraine, specifically with MA. CONCLUSION:
      Further investigation of the G684A variant and the Notch 3 gene is warranted to
      understand their role in migraine.

PMID- 20813782
TI  - Visual metacontrast masking in migraine.
AB  - BACKGROUND: In visual metacontrast masking, the visibility of a brief target
      stimulus can be reduced substantially if it is preceded (forward masking) or
      followed (backward masking) by a non-overlapping mask. These effects have been
      attributed to inhibitory processes within the visual system. Two previous studies
      have used metacontrast masking to assess inhibitory function in migraine and
      control groups, however, each used different types of masking and obtained
      different results. SUBJECTS AND METHODS: Forward, backward and combined forward
      and backward masking were compared in migraine (15 with visual aura, 15 without)
      and control (n = 15) groups. Baseline trials were also included (target only).
      RESULTS: For all types of masking, both migraine groups were more accurate than
      the control group. When performance for the masking trials was expressed relative
      to baseline, however, there were no significant group differences. Performance in
      certain conditions nevertheless correlated significantly with migraine frequency
      and with the recency of the last attack. CONCLUSIONS: The inhibitory processes
      involved in the masking tasks employed in this study do not appear to be impaired
      in migraine. Their better overall performance may reflect a sensitivity
      difference, perhaps as a consequence of a heightened neuronal response, which
      varies with the migraine cycle.

PMID- 20813783
TI  - A trans-cultural comparison of the organisation of care at headache centres world
      wide.
AB  - BACKGROUND: The need to provide better outcomes for patients with headache, and
      to minimise the costs involved in doing so, has prompted the search for new modes
      of service delivery by exploring the service organisation and nursing role from
      various cultural, economic and global perspectives. MATERIALS AND METHODS: This
      study was based on comparisons with the UK headache service up to 2007, the point
      at which this study was set up. This UK service was based at the National
      Hospital for Neurology and Neurosurgery (NHNN, UCLH Trust). Data were obtained
      from US headache centres in 2008 and from centres in Copenhagen, Bangkok, Sydney
      and Porto Alegre in 2009. RESULTS: A comparison shows the key components of
      services at all centres showing the team structure and size of service. Prominent
      features at the centres included: team-working, regular meetings, educational
      input, good access and communication among team members, headache-trained
      neurologists, specialist nursing at most centres, and the input of psychological
      and physical therapists at some centres. CONCLUSIONS: The problems of tertiary
      headache care are very similar throughout the world and seem to transcend ethnic,
      cultural and economic considerations.

PMID- 20813784
TI  - Disability, HRQoL and resource use among chronic and episodic migraineurs:
      results from the International Burden of Migraine Study (IBMS).
AB  - BACKGROUND: Migraine imposes significant burden on patients, their families and
      health care systems. In this study, we compared episodic to chronic migraine
      sufferers to determine if migraine status predicted headache-related disability,
      health-related quality of life (HRQoL) and health care resource utilization.
      METHODS: A Web-based survey was administered to panelists from nine countries.
      Participants were classified as having chronic migraine (CM), episodic migraine
      (EM) or neither using a validated questionnaire. Data collected and then analyzed
      included sociodemographics, clinical characteristics, Migraine Disability
      Assessment, Migraine-Specific Quality of Life v2.1, Patient Health Questionnaire
      and health care resource utilization. FINDINGS: Of the respondents, 5.7% had CM
      and 94.3% had EM, with CM patients reporting significantly more severe
      disability, lower HRQoL, higher levels of anxiety and depression and greater
      health care resource utilization compared to those with EM. INTERPRETATION: These
      results provide evidence that will enhance our understanding of the factors
      driving health care costs and will contribute to development of cost-effective
      health care strategies.

PMID- 20813785
TI  - Arabidopsis thaliana, a plant model organism for the neuronal microtubule
      cytoskeleton?
AB  - The microtubule cytoskeleton is an important component of both neuronal cells and
      plant cells. While there are large differences in the function of microtubules
      between the two groups of organisms, for example plants coordinate the ordered
      deposition of cellulose through the microtubule cytoskeleton, there are also some
      notable similarities. It is suggested that Arabidopsis thaliana, with its
      superior availability of knockout lines, may be a suitable model organism for
      some aspects of the neuronal microtubule cytoskeleton. Some cellular processes
      that involve the neuronal microtubule cytoskeleton including neurotransmitter
      signalling and neurotrophic support may have homologous processes in plant cells.
      A number of microtubule-associated proteins (MAPs) are conserved, including
      katanin, EB1, CLASP, spastin, gephyrin, CRIPT, Atlastin/RHD3, and ELP3. As a
      demonstration of the usefulness of a plant model system for neuronal biology, an
      analysis of plant tubulin-binding proteins was used to show that Charcot-Marie
      Tooth disease type 2D and spinal muscular atrophy may be due to microtubule
      dysfunction and suggest that indeed the plant microtubule cytoskeleton may be
      particularly similar to that of motor neurons as both are heavily reliant upon
      motor proteins.

PMID- 20813786
TI  - An alternative pathway for ureide usage in legumes: enzymatic formation of a
      ureidoglycolate adduct in Cicer arietinum and Phaseolus vulgaris.
AB  - Ureidoglycolate is an intermediate in the degradation of the ureides, allantoin
      and allantoate, found in many organisms. In some leguminous plant species these
      compounds are used to transport recently fixed nitrogen in the root nodules to
      the aerial parts of the plant. In the present study, it was demonstrated that
      purified ureidoglycolases from chickpea (Cicer arietinum) and French bean
      (Phaseolus vulgaris) do not produce glyoxylate, and can use phenylhydrazine as a
      substrate with K(m) values of 4.0 mM and 8.5 mM, respectively. Furthermore, these
      enzymes catalyse the transfer of the ureidoglycolyl group to phenylhydrazine to
      produce ureidoglycolyl phenylhydrazide, which degrades non-enzymatically to
      glyoxylate phenylhydrazone and urea. This supports their former classification as
      ureidoglycolate urea-lyases. The enzymatic reaction catalysed by the
      characterized ureidoglycolases uncovered here can be viewed as a novel type of
      phenylhydrazine ureidoglycolyl transferase. The implications of these findings
      for ureide metabolism in legume nitrogen metabolism are discussed.

PMID- 20813787
TI  - Conventional and novel biomarkers of treatment outcome in patients with
      acromegaly: discordant results after somatostatin analog treatment compared with
      surgery.
AB  - CONTEXT: Control of disease activity in acromegaly is critical, but the
      biochemical definitions remain controversial. OBJECTIVE: To compare traditional
      and novel biomarkers and health status in patients with acromegaly treated with
      either surgery alone or somatostatin analog (SA). DESIGN AND METHODS: Sixty-three
      patients in long-term remission based on normalized total IGF1 levels after
      surgery alone (n=36) or SA (n=27) were studied in a cross-sectional manner. The
      groups were comparable at diagnosis regarding demographic and biochemical
      variables. Each subject underwent 3 h of serum sampling including a 2-h oral
      glucose tolerance test (OGTT). Health status was measured by two questionnaires:
      EuroQoL and Acrostudy (Patient-assessed-Acromegaly symptom questionnaire (PASQ)).
      RESULTS: Total and bioactive IGF1 (MUg/l) levels were similar (total: 185 +/- 10
      (SA) versus 171 +/- 8 (surgery) (P=0.28); bioactive: 1.9 +/- 0.2 vs 1.9 +/- 0.1
      (P=0.70)). Suppression of total and free GH (MUg/l) during OGTT was blunted in
      the SA group (total GH(nadir): 0.59 +/- 0.08 (SA) versus 0.34 +/- 0.06 (surgery)
      (P=0.01); free GH(nadir): 0.43 +/- 0.06 vs 0.19 +/- 0.04 (P<0.01)). The insulin
      response to OGTT was delayed, and the 2-h glucose level was elevated during SA
      treatment (P=0.02). Disease-specific health status was better in patients after
      surgery (P=0.02). CONCLUSIONS: i) Despite similar and normalized IGF1 levels, SA
      treatment compared with surgery alone was associated with less suppressed GH
      levels and less symptom relief; ii) this discordance may be due to specific
      suppression of hepatic IGF1 production by SA; iii) we suggest that biochemical
      assessment during SA treatment should include both GH and IGF1.

PMID- 20813788
TI  - Post-ablative serum thyroglobulin is an independent predictor of recurrence in
      low-risk differentiated thyroid carcinoma: a 16-year follow-up study.
AB  - OBJECTIVE: To study whether post-surgical and/or post-ablative thyroglobulin (Tg)
      concentrations may serve as independent predictors of disease recurrence in
      patients treated for TNM stage I or II well-differentiated thyroid carcinoma
      (WDTC). DESIGN: An observational retrospective study with a median follow-up of
      16 years (range 10-24). PATIENTS AND MEASUREMENTS: Post-operative and post
      ablative Tg concentrations, age, tumour size, local infiltration and nodal
      metastasis at primary surgery as well as disease recurrences and cancer-specific
      deaths were evaluated in 495 low-risk (TNM stages I and II) patients, the
      majority of whom had total thyroidectomy and radioactive iodine remnant ablation
      as initial treatment. RESULTS: Fifty-one patients (10.3%) experienced disease
      recurrence during follow-up. In multiple logistic regression analysis, post
      ablative Tg concentrations (odds ratio (OR) 3.72, confidence interval (CI) 1.71
      8.05, P=0.0009) and local infiltration on primary surgery (OR 2.66, CI 1.03-6.90,
      P=0.04) were the only independent predictors of recurrence. CONCLUSIONS: Post
      ablative Tg concentration is a strong predictor of disease recurrence in WDTC.

PMID- 20813789
TI  - Prevalence and predictors of vitamin D insufficiency in women of reproductive age
      living in northern latitude.
AB  - OBJECTIVE: This study assessed the prevalence of vitamin D deficiency (serum 25
      hydroxyvitamin D (25OHD) <= 50 nmol/l) and insufficiency (serum 25OHD 51-74
      nmol/l) during summer and the predictors of serum 25OHD in young women of
      reproductive age. DESIGN: Cross-sectional study. METHODS: Between May and
      September 2006, 153 healthy, ambulatory and essentially Caucasian women, aged 18
      41 years, were recruited. Serum 25OHD and parathyroid hormone (PTH) levels were
      measured, and questionnaires were evaluated. RESULTS: About 3.9% of women had
      serum 25OHD <= 50 nmol/l with an additional 26.8% in the insufficient range. Most
      women (56.9%) had their blood sampled in September. Month of blood collection
      significantly influenced serum 25OHD. Body mass index (BMI) was inversely
      associated with serum 25OHD, while traveling to a warmer climate during
      winter/spring and using oral contraceptive pills (OCP) were associated with
      higher serum 25OHD. Sunscreen was used by 77.8% of women, but only 3.3% reported
      consuming vitamin D supplements. BMI, serum PTH, travel to a warmer climate, and
      OCP use were independently and significantly associated with serum 25OHD, after
      adjustment for the month of sampling, and explained 40% of the variance in serum
      25OHD. CONCLUSIONS: In Canada, the prevalence of vitamin D insufficiency is
      relatively high (30%) during summer in healthy women of reproductive age. Given
      the expected decrease in serum 25OHD during winter and the low consumption of
      vitamin D supplements, a high prevalence of vitamin D deficiency and
      insufficiency is to be anticipated during winter, except maybe for those
      traveling to a warmer climate.

PMID- 20813790
TI  - The relative contribution of prosthetic gradients, systemic arterial pressure,
      and pulse pressure to the left ventricular pressure in patients with aortic
      prosthetic valves.
AB  - AIMS: aortic valve replacement (AVR) in patients with aortic stenosis reduces the
      left ventricular (LV) pressure and the LV mass. However, residual LV hypertrophy
      at follow-up is a common finding with negative prognostic impact. In the present
      study, we investigate the contribution of the prosthesis (size, type, and
      gradients) and the load opposed by the arterial system to the mean LV pressure
      (MLVP). METHODS AND RESULTS: twenty-five patients with a bileaflet mechanical (n
      = 12, size 19-27) or stented biological (size 21-25) valve were included. After
      weaning from bypass, continuous Doppler recordings (transoesophageal transducer)
      and simultaneous LV and aortic pressure measurements were performed (high
      fidelity catheters). The mean prosthesis gradients with catheter or Doppler were
      moderately correlated to MLVP (R(2) = 0.40 and 0.34, P = 0.002 and <0.0001). In a
      multiple regression model, the relationship between MLVP and prosthesis gradient,
      mean blood pressure, and pulse pressure was strong for both mechanical and
      biological valves. Using catheter prosthesis gradients, we could explain 97% of
      the variability in MLVP and when using Doppler gradients 91%. CONCLUSION: in the
      present study of patients with aortic prosthetic valves, we demonstrate the
      importance of the load opposed by the arterial system for the LV pressure. Our
      findings suggest that the MLVP can be estimated from easily obtainable Doppler
      data and blood pressure measurements. In analysing predictors of LV mass
      regression, morbidity, and mortality following AVR, the equations might be of
      interest.

PMID- 20813791
TI  - Prominence of the Eustachian valve in paradoxical embolism.
AB  - AIMS: to investigate the relationship between Eustachian valve (EV) length and
      degree of atrial septal movement in patients with patent foramen ovale (PFO) and
      presumed paradoxical cerebral embolism. PFO is a well-established risk factor for
      cryptogenic stroke. However, due to the high prevalence of PFO, many of these are
      bystanders rather than true pathological entities. Other studies have sought to
      define which patients with PFO are particularly at risk of cryptogenic stroke by
      measuring various parameters of right atrial anatomy. We investigated the
      relationship between EV length and atrial septal movement. METHODS AND RESULTS:
      measurements of EV length and atrial septal movement were made prospectively from
      72 consecutive patients referred to our centre for PFO closure following presumed
      cryptogenic stroke, by intracardiac phased array echocardiography. The most
      significant finding from this study was that patients with fewer than 10 mm
      atrial septal movement had significantly longer EVs than those in whom there was
      >10 mm septal movement (P = 0.003). The mean EV length with >10 mm septal
      movement is 6.35 mm, and 13.33 mm with fewer than 10 mm movement. The prevalence
      of septal movement beyond 10 mm was significantly less in our series than in
      previously published papers. CONCLUSION: we propose that while a large degree of
      atrial septal movement significantly increases propensity to cerebral embolism in
      patients with PFO, its absence does not negate this risk. We have shown that long
      EV may function independently from atrial septal movement to potentiate
      paradoxical embolism.

PMID- 20813792
TI  - Serum iron parameters, HFE C282Y genotype, and cognitive performance in older
      adults: results from the FACIT study.
AB  - Although iron homeostasis is essential for brain functioning, the effects of iron
      levels on cognitive performance in older individuals have scarcely been
      investigated. In the present study, serum iron parameters and hemochromatosis
      (HFE) C282Y genotype were determined in 818 older individuals who participated in
      a 3-year randomized, placebo-controlled double-blind trial examining the effects
      of folic acid on carotid intima-media thickness. All participants had slightly
      elevated homocysteine levels and were vitamin B12 replete. Cognitive functioning
      was assessed at baseline and after 3 years by means of a neuropsychological test
      battery. At baseline, increased serum ferritin was associated with decreased
      sensorimotor speed, complex speed, and information-processing speed and increased
      serum iron was associated with decreased sensorimotor speed. Cognitive
      performance over 3 years was not associated with HFE C282Y genotype or iron
      parameters. In conclusion, serum iron parameters do not show a straightforward
      relationship with cognitive functioning, although elevated iron levels may
      decrease cognitive speed in older individuals susceptible to cognitive
      impairment.

PMID- 20813793
TI  - Heritability estimates of endophenotypes of long and health life: the Long Life
      Family Study.
AB  - BACKGROUND: Identification of gene variants that contribute to exceptional
      survival may provide critical biologic information that informs optimal health
      across the life span. METHODS: As part of phenotype development efforts for the
      Long Life Family Study, endophenotypes that represent exceptional survival were
      identified and heritability estimates were calculated. Principal components (PCs)
      analysis was carried out using 28 physiologic measurements from five trait
      domains (cardiovascular, cognition, physical function, pulmonary, and metabolic).
      RESULTS: The five most dominant PCs accounted for 50% of underlying trait
      variance. The first PC (PC1), which consisted primarily of poor pulmonary and
      physical function, represented 14.3% of the total variance and had an estimated
      heritability of 39%. PC2 consisted of measures of good metabolic and
      cardiovascular function with an estimated heritability of 27%. PC3 was made up of
      cognitive measures (h(2) = 36%). PC4 and PC5 contained measures of blood pressure
      and cholesterol, respectively (h(2) = 25% and 16%). CONCLUSIONS: These PCs
      analysis-derived endophenotypes may be used in genetic association studies to
      help identify underlying genetic mechanisms that drive exceptional survival in
      this and other populations.

PMID- 20813794
TI  - Low physical function predicts either 2-year weight loss or weight gain in
      healthy community-dwelling older adults. the NuAge Longitudinal Study.
AB  - OBJECTIVES: Weight change in older adults affects physical function (PF).
      However, data suggest that, conversely, PF may be a determinant of weight change.
      Our objective was to assess the role of baseline PF as a predictor of 2-year
      weight loss (WL) and weight gain (WG) >= 5% among healthy well-functioning
      community-dwelling older adults. METHODS: The NuAge cohort (67-84 years) was
      classified into three groups according to the percent weight change over a 2-year
      follow-up: weight stable (weight change <= 2%; n = 629), WL >= 5% (n = 189), and
      WG >= 5% (n = 111). A summary measure of baseline PF was computed (sum of biceps,
      quadriceps, and grip strength, timed up and go, chair stand, normal and maximal
      gait speed, and balance performance scores [individual test score range = 0-4];
      PF score range = 0-32). Multivariable logistic regression models separately
      assessed the relationships between baseline PF and 2-year WL and WG >= 5%.
      RESULTS: Baseline PF was worse in both the WL (p < .001) and the WG (p = .001)
      groups compared with the weight stable group. In models adjusting for sex, age,
      body mass index, energy intake, depressive symptoms, and other significantly
      associated covariates, each 1-unit increase in standard deviation of PF was
      associated with decreased risk of either 2-year WL (odds ratio = 0.79, 95% CI =
      0.63-0.99, p = .043) or WG (odds ratio = 0.74, 95% CI = 0.55-0.99, p = .041).
      CONCLUSIONS: Low baseline PF was an independent common predictor of 2-year WL and
      WG >= 5% in the healthy well-functioning community-dwelling elderly population.
      Whether PF is an early cause or marker of weight change in this population
      remains to be determined.

PMID- 20813795
TI  - Protective effects of thymoquinone against methotrexate-induced testicular
      injury.
AB  - Thymoquinone is the major active component derived from Nigella sativa.
      Methotrexate is a folic acid antagonist widely used in clinic. Aim of this study
      was to investigate the possible protective role of thymoquinone on testicular
      toxicity of methotrexate. Experiments were performed on male C57BL/6 mice (6
      weeks old, 20 +/- 2 g). The animals were divided into four groups with six mice
      in each group. Equivalent volumes of saline were injected intraperitoneally
      (i.p.) in the control group. In the thymoquinone group, mice received
      thymoquinone i.p. with a dose of 10 mg/kg/day for 4 days. Mice in the
      methotrexate group received single dose of methotrexate i.p., with a dose of 20
      mg/kg. Finally, in the methotrexate plus thymoquinone group, in the first and the
      following 3 days after methotrexate administration, thymoquinone was injected
      with a dose of 10 mg/kg/day, i.p. At the end of the experiment, the left testis
      was quickly removed and divided into two parts for histological examination and
      biochemical analysis. Methotrexate alone increased total antioxidant capacity and
      myeloperoxidase activity compared to the controls. Thymoquinone treatment
      decreased total antioxidant capacity and prevented the increase in the
      myeloperoxidase activity. Light microscopy showed in mice that receiving
      methotrexate resulted in interstitial space dilatation, edema, severe disruption
      of the seminiferous epithelium and reduced diameter of the seminiferous tubules.
      Administration of thymoquinone reversed histological changes of methotrexate
      significantly. We suggest that thymoquinone use may decrease the destructive
      effects of methotrexate on testicular tissue of patients using this agent.

PMID- 20813796
TI  - Liver transplantation in systemic lupus erythematosus: case report and review of
      the literature.
AB  - Severe liver involvement requiring liver transplantation is a rare complication
      in systemic lupus erythematosus (SLE), but very few cases have been reported. We
      describe a 39-year-old woman with SLE who underwent successful liver
      transplantation due to acute liver failure. The patient persisted without
      reactivation of SLE and with good long-term survival. Management and diagnosis
      considerations are reviewed.

PMID- 20813797
TI  - Premature aortic stiffness in systemic lupus erythematosus by transesophageal
      echocardiography.
AB  - To assess aortic stiffness by transesophageal echocardiography (TEE) and to
      determine its clinical predictors and relation to age, blood pressure, renal
      function, and atherosclerosis, 50 patients with systemic lupus erythematosus
      (SLE), 94% women, with a mean age of 38 +/- 12 years, and 22 age and gender
      matched healthy controls underwent clinical and laboratory evaluations and
      multiplane TEE to assess stiffness, intima-media thickness (IMT), and plaques of
      the proximal, mid, and distal descending thoracic aorta. Stiffness at each level
      and overall aortic stiffness by the pressure-strain elastic modulus was higher in
      patients than in controls after adjusting for age (overall, 8.25 +/- 4.13 versus
      6.1 +/- 2.5 Pascal units, p = 0.01). Patients had higher aortic stiffness than
      controls after adjusting both groups to the same mean age, blood pressure,
      creatinine, and aortic IMT (p = 0.005). Neither IMT nor plaques were predictors
      of aortic stiffness. Moreover, normotensive patients, those without aortic
      plaques, and non-smokers had higher stiffness than controls (all p < 0.05). Age
      at SLE diagnosis and non-neurologic damage score were the only SLE-specific
      independent predictors of aortic stiffness (both p <= 0.01). Thus, increased
      aortic stiffness is an early manifestation of lupus vasculopathy that seems to
      precede the development of hypertension and atherosclerosis.

PMID- 20813798
TI  - The embryotoxicity of sera from patients with autoimmune diseases on post
      implantation rat embryos in culture persists during remission and is not related
      to oxidative stress.
AB  - We evaluated the embryolethality and embryotoxicity of sera from patients
      suffering from autoimmune diseases during remission on post-implantation rat
      embryos cultured on these sera and determined the association between the
      patients' clinical history, high blood levels of specific antibodies,
      medications, and oxidative stress parameters. One hundred and eighty, 10.5-day
      old rat embryos were cultured in their yolk sacs in 33 sera of systemic lupus
      erythematosus (SLE)/antiphospholipid syndrome (APS) patients, and compared with
      84 embryos cultured in rat sera and 88 embryos cultured in control human sera.
      The sera proved to be lethal and embryotoxic but not teratogenic resulting in
      smaller yolk sacs and embryos, lower protein level and lower developmental score.
      Significantly less embryos cultured in 'toxic' SLE/APS sera had peak 2 of low
      molecular weight antioxidants (LMWA) wave, implying a delayed maturation of the
      antioxidant defense. Lower peak 1 of LMWA correlated with a history of recurrent
      abortions. Embryonic levels of superoxide dismutase (SOD) and catalase (CAT) did
      not correlate with sera toxicity, patients' clinical history or specific
      antibodies. We conclude that SLE/APS patients' clinical remission did not prevent
      death or developmental delay accompanied by later appearance of peak 2 of LMWA in
      post-implantation rat embryo cultures. The normal levels of the antioxidant
      enzymes evaluated may indicate that sera toxicity is not related to oxidative
      stress.

PMID- 20813799
TI  - Health in All Policies: from rhetoric to action.
AB  - AIMS: The fact that health is largely constructed outside the remits of the
      health sector has been known for a long time. However, implementing intersectoral
      health policies is difficult. The aim of this article is to study possibilities
      for strengthening the implementation of Health in All Policies (HiAP) approach.
      METHODS: The article analyses earlier efforts in intersectoral health policy
      making and adapts Kingdon's theory on policy change for exploring opportunities
      and challenges for strengthening HiAP approach. RESULTS: Opportunities for HiAP
      can be identified by analysing possibilities for amending health determinants on
      the one hand, and by analysing policy trends, proposals, and actors, especially
      in fields other than health, on the other. Four basic strategies for HiAP are
      identified, namely: health strategy, win-win strategy, cooperation strategy, and
      damage limitation strategy. Their strengths in various situations are explored.
      Using an adaptation of Kingdon's framework, possibilities for creating
      opportunities for HiAP by raising health issues on the agenda, developing
      appropriate tools and by creating conducive momentums are discussed. CONCLUSIONS:
      It is concluded that systematic efforts of experts in public health, health
      policy, and international health are important in identifying and prioritising
      the needs for HiAP, in analysing health implications of policies and policy
      proposals and making these understood by the policy-makers, as well as in
      suggesting feasible solutions. Improving health literacy of the public, the
      policy-makers, and the media is key for improved understanding on health
      implications of policies. Participatory and transparent approaches to policy
      making are prerequisites for strengthening HiAP.

PMID- 20813800
TI  - Invited commentary: a sunbed epidemic?
AB  - The Icelandic study of melanoma trends by Hery et al. in this issue of the
      Journal (Am J Epidemiol. 2010;172(7):762-767) is a fascinating analysis of an
      ecologic association. The authors noted a sharp increase in melanoma incidence
      that appeared to lag a few years behind the increased prevalence of sunbeds in
      Iceland. Caution, however, must be exercised in interpreting the data because of
      the lack of understanding of emissions of ultraviolet radiation from sunbeds and
      the ecologic nature of the data.

PMID- 20813801
TI  - A melanoma epidemic in Iceland: possible influence of sunbed use.
AB  - Since 1980, sunbed use and travel abroad have dramatically increased in Iceland
      (64 degrees -66 degrees N). The authors assessed temporal trends in melanoma
      incidence by body site in Iceland in relation to sunbed use and travel abroad.
      Using joinpoint analysis, they calculated estimated annual percent changes
      (EAPCs) and identified the years during which statistically significant changes
      in EAPC occurred. Between 1954 and 2006, the largest increase in incidence in men
      was observed on the trunk (EAPC = 4.6%, 95% confidence interval: 3.2, 6.0). In
      women, the slow increase in trunk melanoma incidence before 1995 was followed by
      a significantly sharper increase in incidence, mainly among women aged less than
      50 years, resembling an epidemic incidence curve (1995-2002: EAPC = 20.4%, 95%
      confidence interval: 9.3, 32.8). In 2002, the melanoma incidence on the trunk was
      higher than the incidence on the lower limbs for women. Sunbed use in Iceland
      expanded rapidly after 1985, mainly among young women, and in 2000, it was
      approximately 2 and 3 times the levels recorded in Sweden and in the United
      Kingdom, respectively. Travels abroad were more prevalent among older Icelanders.
      The high prevalence of sunbed use probably contributed to the sharp increase in
      the incidence of melanoma in Iceland.

PMID- 20813803
TI  - Alcoholic beverages and prostate cancer in a prospective US cohort study.
AB  - Despite numerous investigations, the correlation between alcohol consumption and
      prostate cancer risk remains uncertain. This report investigated the association
      between alcohol use and prostate cancer risk in a prospective cohort study of
      294,707 US men aged 50-71 years in 1995-1996. Cox proportional hazards regression
      models with hazard ratios and 95% confidence intervals were adjusted for
      characteristics including age, race, body mass index, physical activity, and
      family history of prostate cancer, as well as testing for prostate-specific
      antigen and a digital rectal examination. There were 15,327 nonadvanced and 1,900
      advanced prostate cancers identified through 2003 and 514 fatal cases through
      2005. Risk of nonadvanced prostate cancer was 25% higher for men consuming >=6
      drinks daily (hazard ratio = 1.25, 95% confidence interval: 1.13, 1.37), 19%
      higher for men consuming 3-<6 drinks daily, and 6% higher for men consuming up to
      3 drinks daily, compared with nondrinkers. The association between alcohol
      consumption and nonadvanced prostate cancer risk did not differ appreciably by
      age, family history of prostate cancer, smoking status, body mass index, or self
      reported prostate-specific antigen testing and digital rectal examination (the
      latter available for >60% of respondents). The authors observed no association
      between alcohol intake and advanced prostate cancer and an inverse association
      with fatal prostate cancer among heavy drinkers. These findings suggest that
      higher alcohol consumption modestly increases nonadvanced prostate cancer risk.

PMID- 20813804
TI  - ESHRE PGD Consortium data collection X: cycles from January to December 2007 with
      pregnancy follow-up to October 2008.
AB  - The 10th report of the European Society of Human Reproduction and Embryology
      (ESHRE) PGD Consortium is presented, documenting cycles collected for the
      calendar year 2007 and follow-up of the pregnancies and babies born until October
      2008 which resulted from these cycles. Since the beginning of the data
      collections there has been a steady increase in the number of cycles, pregnancies
      and babies reported annually. For data collection X, 57 centres participated,
      reporting on 5887 cycles to oocyte retrieval (OR), along with details of the
      follow-up on 1516 pregnancies and 1206 babies born. A total of 729 OR were
      reported for chromosomal abnormalities, 110 OR for sexing for X-linked diseases,
      1203 OR for monogenic diseases, 3753 OR for preimplantation genetic screening and
      92 OR for social sexing. Data X is compared with the cumulative data for data
      collections I-IX.

PMID- 20813805
TI  - Interferon gamma contributes to preimplantation embryonic development and to
      implantation site structure in NOD mice.
AB  - BACKGROUND: Pre-eclampsia, a syndrome usually accompanied by incomplete spiral
      arterial modification, occurs at an increased frequency in diabetic women.
      Hyperglycemia in non-obese type 1 diabetic (NOD) mice impairs gestational spiral
      arterial remodeling despite high local levels of interferon gamma (Ifng), the
      triggering cytokine in mice. Pregnancies in NOD.Ifng(-/-) mice were assessed to
      investigate this issue. METHODS: Fecundity was assessed using the breeding
      history, flushing of preimplantation embryos and histological and morphometric
      studies of implantation sites in normoglycemic (n-) and hyperglycemic (d-)
      females of NOD.Ifng(-/-) and NOD genotypes. RESULTS: NOD.Ifng(-/-) but not NOD
      mice are mostly infertile. In NOD.Ifng(-/-), copulation often does not result in
      a post-implantation pregnancy. Defective fertilization and delayed
      preimplantation development limit n-NOD.Ifng(-/-) fertility, and both mechanisms
      are exacerbated by hyperglycemia. At mid-gestation, implantation sites in n
      NOD.Ifng(-/-) and n-NOD mice are histologically similar. However, in d-NOD.Ifng(
      /-), there is minimal development of spiral arteries, hypertrophy of the
      myometrial region containing uterine Natural Killer (uNK) cells and a deficit in
      cytoplasmic granule formation in the uNK cells. CONCLUSIONS: Ifng contributes to
      the success of fertilization and to the rate of preimplantation mouse embryo
      development in normogylcemic and hyperglycemic pregnancies. A physiological role
      for this cytokine in human preimplantation development merits investigation.

PMID- 20813806
TI  - Effect of dienogest administration on angiogenesis and hemodynamics in a rat
      endometrial autograft model.
AB  - BACKGROUND: We aimed to establish an endometrial autograft model in rats that
      would allow for repetitive in vivo analyses of angiogenesis. Dienogest (DNG) is
      an orally active progestin used for the treatment of endometriosis. We
      investigated whether DNG would affect angiogenesis of the ectopic endometrium in
      our model. METHODS: Mechanically isolated endometrial fragments were transplanted
      into dorsal skinfold chambers in rats. We analyzed the effect of DNG on
      angiogenesis of the ectopic endometrium on Days 0, 2, 4, 7, 10 and 14 after
      transplantation using intravital fluorescence microscopy. RESULTS: The DNG
      administered group showed significant suppression of angiogenesis of endometrial
      autografts, as indicated by the reduced size of the microvascular network and
      decreased microvessel density compared with those of control animals. The newly
      formed microvessels of the DNG-administered group showed consistently elevated
      diameters and centerline red blood cell velocity was decreased.
      Immunohistochemistry revealed a significant reduction in the level of
      perivascular alpha-smooth muscle actin within endometrial grafts of the DNG
      administered group. CONCLUSIONS: DNG inhibited angiogenesis of the ectopic
      endometrium, with confirmed structural changes in the microvessels.

PMID- 20813807
TI  - Embryo and uterine influences on IVF outcomes: an analysis of a UK multi-centre
      cohort.
AB  - BACKGROUND: In order to optimize IVF strategies, particularly with the use of
      single embryo transfer, good predictive models are required. Here, we develop a
      model to allow such prediction, and the structure of the models point to more
      general conclusions about the mode of action of prognostic factors. METHODS:
      Anonymized data from consecutive embryo transfers in five IVF centres in the UK
      for the 2000-2005 period were extracted and the morphological grade based on
      common scoring criteria was included. There were 16 096 (12 487 fresh and 3609
      frozen) transfers, for 8775 couples, available for analysis. Live birth data were
      fitted to a model with separate sub-models for embryo and recipient effects [the
      'Embryo-Uterus' (EU) model]. All covariates were included, with sub-model
      selection using Akaike's information criterion. RESULTS: Age, number of embryos
      created, attempt number, previous history of pregnancy, duration of infertility,
      day of transfer and tubal diagnosis were all identified as significant prognostic
      factors, along with embryo grade and growth rate. Frozen transfers were
      substantially less likely to lead to a live birth with odds ratios of 1/3 to 1/2
      compared with fresh transfers, with no evidence of differential loss for any
      particular patient group. Age acts predominantly through the embryo component
      with only a weak effect on the uterus. The embryo number, attempt number,
      previous pregnancies and duration of infertility act predominantly through the
      uterine environment. Both sub-models show significant heterogeneity between
      centres. CONCLUSIONS: The EU modelling framework has generated a model for
      predicting outcomes of embryo-transfer procedures, subject to the limitations of
      routinely collected data. With this large data set, the model allows
      identification of factors that act specifically on embryo viability or maternal
      receptivity. Variability in the two components between centres with similar
      overall outcomes suggests scope for further optimization of IVF treatment.

PMID- 20813808
TI  - Faecal carriage of multidrug-resistant Gram-negative bacilli during a non
      outbreak situation in a French university hospital.
AB  - OBJECTIVES: To determine the prevalence of multidrug-resistant (MDR) Gram
      negative bacilli and extended spectrum beta-lactamase (ESBL)-producing isolates
      in stool specimens obtained from patients hospitalized for acute diarrhoea in a
      French university hospital. METHODS: Bacteria in stool specimens were screened
      for ESBL production on Drigalski agar supplemented with ceftazidime, ESBL
      CHROMagar((r)) and CTX CHROMagar((r)) media and confirmed by the double-disc
      synergy test. Genetic detection was performed by PCR and sequencing with
      bacterial DNA extracted from isolates. RESULTS: The presence of MDR bacteria was
      markedly high (96 of 303 patients, 31.7%). The majority of MDR bacteria were
      Enterobacter cloacae (44, 38%) and Escherichia coli (32, 28%). Moreover, the
      prevalence of ESBL and CTX-M producers among all included patients was 15.8% and
      5.9%, respectively. The clone E. coli O25b : H4-ST131 was detected in 63% of CTX
      M strains. Surprisingly, 16 carbapenemases (5.3% of patients) were isolated.
      CONCLUSIONS: The study revealed the wide dissemination of MDR bacteria, including
      carbapenemase producers, in a French hospital during a non-outbreak situation.
      Public health efforts to combat emergence and dissemination of MDR organisms need
      to be developed.

PMID- 20813809
TI  - Impact of hepatitis C and liver fibrosis on antiretroviral plasma drug
      concentrations in HIV-HCV co-infected patients: the HEPADOSE study.
AB  - OBJECTIVES: To compare plasma antiretroviral concentrations in HIV-HCV co
      infected and in matched HIV mono-infected patients. METHODS: This was a cross
      sectional, observational study. Antiretroviral trough concentrations (C(min)) in
      plasma were measured in HIV-HCV co-infected patients with liver disease
      documented by liver biopsy, matched with HIV mono-infected patients according to
      gender and antiretroviral treatment. C(min) values in serum were measured using
      an HPLC method. Statistical analysis was performed using the Wilcoxon test.
      RESULTS: Seventy-three HIV-HCV co-infected patients and 66 HIV-infected patients
      were enrolled; 70% of patients were receiving a protease inhibitor (PI)- and 30%
      a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. Among the
      73 co-infected patients, 27 had a fibrosis score (Fibrotest((r))) of F4. Abacavir
      was the only nucleoside reverse transcriptase inhibitor whose trough
      concentrations differed between the co-infected and mono-infected groups. PI
      median plasma C(min) values were not different in the two groups, except for
      lopinavir, with a lower C(min) in the co-infected group than in the HIV-infected
      group (median 3673 versus 5990 ng/mL, P=0.04), and nelfinavir, with significantly
      higher concentrations in the co-infected group. Seventy-five percent of co
      infected patients scoring F4, 33% of those scoring F0-F3 and 12% of HIV-infected
      patients were underdosed (P=0.02). Co-infected patients receiving an NNRTI had a
      higher plasma C(min) than HIV-infected patients; median C(min) was 3583 versus
      1494 ng/mL (P=0.025) and 5331 versus 3954 ng/mL (P=0.10) for efavirenz and
      nevirapine, respectively. Overall, there was a greater proportion of co-infected
      patients with high concentrations of both NNRTIs (15/23) compared with HIV mono
      infected patients (5/21) (P=0.008), especially in co-infected patients with an
      advanced liver fibrosis stage. CONCLUSIONS: Median plasma C(min) values differed
      significantly between HIV and HIV-HCV co-infected patients for abacavir,
      lopinavir and efavirenz. NNRTIs were strongly overdosed in HIV-HCV co-infected
      patients.

PMID- 20813811
TI  - Horse receiving acupuncture.

PMID- 20813812
TI  - Acupuncture needle sensation: the emerging evidence.

PMID- 20813813
TI  - Efficacy of ah shi point acupuncture on acne vulgaris.
AB  - BACKGROUND: Ah shi point acupuncture involves inserting needles at painful or
      pathological sites. OBJECTIVE: To evaluate the efficacy of ah shi point and
      general acupuncture point treatment of acne vulgaris. METHODS: 36 subjects were
      recruited and randomised in a double-blind (patient-blind and observer-blind)
      controlled trial to receive acupuncture either at general acupuncture points
      only, or at both general acupuncture points and ah shi points 12 times over 6
      weeks. The subjects were evaluated using the following outcome measurements: an
      inflammatory lesion count, a quality-of-life scale (Skindex-29) and a subjective
      symptom score. RESULTS: After 12 treatment sessions, there was a significant
      reduction in the inflammatory acne lesion counts, the Skindex-29 scores and the
      subjective symptom scores from baseline in both groups, but no significant
      difference between groups. CONCLUSIONS: Acupuncture treatment of moderate acne
      vulgaris was associated with reduction of inflammatory lesions and improvement of
      the quality of life.

PMID- 20813814
TI  - Temporomandibular dysfunction can contribute to aggravation of tension-type
      headache: a case report.
AB  - A 15-year-old girl, who had had occasional tension-type headache, developed,
      rather suddenly and without any obvious reason, severe headache. She was admitted
      to hospital, where examination including CT and magnetic resonance scans did not
      show any abnormality. A visit to her own general practitioner 7 months later
      showed tenderness in the muscle of mastication. The patient was referred to a
      dentist, who diagnosed temporomandibular dysfunction and tension-type headache.
      After three acupuncture treatments, the patient was without headache and remained
      free of headache during the following 6 months.

PMID- 20813817
TI  - Targeting the {alpha} receptor for platelet-derived growth factor as a primary or
      combination therapy in a preclinical model of prostate cancer skeletal
      metastasis.
AB  - PURPOSE: Platelet-derived growth factor alpha (PDGFRalpha) is highly expressed in
      primary prostate cancer and associated skeletal metastases. Here, we tested
      whether targeting this receptor could impair metastatic colonization and
      progression, as well as prolong survival, either as primary or as combination
      therapy. EXPERIMENTAL DESIGN: We used a preclinical animal model of metastasis in
      which PC3-ML human prostate cancer cells are inoculated directly in the blood
      circulation. First, the humanized, monoclonal antibody IMC-3G3 was administered
      to mice bearing established skeletal metastases. Second, we targeted the stromal
      PDGFRalpha with IMC-1E10, an antibody specific for the murine receptor. Third,
      IMC-3G3 and the bisphosphonate zoledronic acid (ZA), administered separately or
      in combination, were tested on the progression of skeletal lesions and overall
      survival. In addition, the ability of IMC-3G3 and ZA to impair initial
      colonization of the bone marrow by prostate cancer cells was investigated.
      RESULTS: The blockade of PDGFRalpha on prostate cancer cells by IMC-3G3 reduces
      the size of established skeletal metastases, whereas the IMC-1E10 antibody
      directed against the stromal PDGFRalpha fails to inhibit metastatic progression.
      IMC-3G3 and ZA, either separately or in combination, significantly slow tumor
      growth and seem to prolong survival. Lastly, the blockade of PDGFRalpha by IMC
      3G3 inhibits the initial phase of bone colonization, whereas ZA is ineffective at
      this stage. CONCLUSION: This study presents compelling evidence that targeting
      PDGFRalpha with IMC-3G3 delays the progression of early metastatic foci and
      reduces the size of more established lesions. In addition, IMC-3G3, either alone
      or in combination with ZA, prolongs survival in animal models.

PMID- 20813818
TI  - Persistent mobility disability after neurotoxic chemotherapy.
AB  - BACKGROUND AND PURPOSE: The impact of cancer and its treatments on balance and
      functional mobility in older adults remains unknown but is increasingly
      important, given the evolution of cancer treatments. Subacute and more persistent
      side effects such as chemotherapy-induced peripheral neuropathy are on the rise,
      and the effects on mobility and balance, as well as the prognosis for resolution
      of any functional deficits, must be established before interventions can be
      trialed. The purpose of this case report is to describe the severity and long
      term persistence of mobility decline in an older adult who received neurotoxic
      chemotherapy. To our knowledge, this is the first case report to describe an
      older adult with chemotherapy-induced peripheral neuropathy using results of
      standardized balance and mobility tests and to focus on prognosis by repeating
      these measures more than 2 years after chemotherapy. CASE DESCRIPTION: An 81-year
      old woman received a neurotoxic agent (paclitaxel) after curative mastectomy for
      breast cancer. Baseline testing prior to taxane therapy revealed a socially
      active woman with no reported functional deficits or neuropathic symptoms, 1.2
      m/s gait speed, and performance at the ceiling on balance and gait portions of a
      standardized mobility measure. OUTCOMES: After 3 cycles, paclitaxel therapy was
      stopped by the oncologist because of neurotoxicity. Declines as large as 50% were
      seen in performance-based measures at 12 weeks and persisted at 2.5 years, and
      the patient reported recurrent falls, cane use, and mobility-related disability.
      DISCUSSION: This case highlights the extent to which function can decline in an
      older individual receiving neurotoxic chemotherapy, the potential for these
      deficits to persist years after treatment is stopped, and the need for physical
      therapy intervention and further research in this population.

PMID- 20813819
TI  - Promoting the use of measurement tools in practice: a mixed-methods study of the
      activities and experiences of physical therapist knowledge brokers.
AB  - BACKGROUND: The use of knowledge brokers (KBs) has been recommended as a
      mechanism to facilitate the use of research evidence in clinical practice.
      However, little has been written regarding the practical implementation of the KB
      role. OBJECTIVES: This article (1) describes the brokering activities of 24
      pediatric physical therapist KBs (in Ontario, Alberta, and British Columbia,
      Canada), and (2) reports KBs' perceptions of the utility of their role and their
      experiences with the brokering process. DESIGN: A mixed-methods research design
      was used in this investigation, which was part of a larger knowledge translation
      (KT) study that demonstrated the effectiveness of using KBs to implement a group
      of evidence-based measurement tools into practice. METHODS: The KBs completed
      weekly activity logs, which were summarized and described. Semi-structured
      telephone interviews with KBs were analyzed qualitatively to provide insight into
      their perceptions of their role and the brokering process. Major interview themes
      were identified and verified through member checking. RESULTS: Brokering
      activities varied considerably as KBs adapted to meet the needs of their
      colleagues. The KBs indicated that they highly valued the connection to the
      research community and spoke of the enthusiastic engagement of their physical
      therapist colleagues (and others in their organization) in the brokering process.
      They discussed the importance of understanding the practice context and
      organizational factors that could affect knowledge transfer. The KBs spoke of the
      need to dedicate time for the role and had a strong sense of the supports needed
      to implement a KB role in future. CONCLUSIONS: Considerable variation in
      brokering activities was demonstrated across KB participants. The KBs perceived
      their role as useful and indicated that organizational commitment is crucial to
      the success of this KT strategy.

PMID- 20813820
TI  - Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum:
      case-control analysis within a UK primary care cohort.
AB  - OBJECTIVE: To examine the hypothesis that risk of oesophageal, but not of gastric
      or colorectal, cancer is increased in users of oral bisphosphonates. DESIGN:
      Nested case-control analysis within a primary care cohort of about 6 million
      people in the UK, with prospectively recorded information on prescribing of
      bisphosphonates. SETTING: UK General Practice Research Database cohort.
      PARTICIPANTS: Men and women aged 40 years or over-2954 with oesophageal cancer,
      2018 with gastric cancer, and 10 641 with colorectal cancer, diagnosed in 1995
      2005; five controls per case matched for age, sex, general practice, and
      observation time. MAIN OUTCOME MEASURES: Relative risks for incident invasive
      cancers of the oesophagus, stomach, and colorectum, adjusted for smoking,
      alcohol, and body mass index. RESULTS: The incidence of oesophageal cancer was
      increased in people with one or more previous prescriptions for oral
      bisphosphonates compared with those with no such prescriptions (relative risk
      1.30, 95% confidence interval 1.02 to1.66; P=0.02). Risk of oesophageal cancer
      was significantly higher for 10 or more prescriptions (1.93, 1.37 to 2.70) than
      for one to nine prescriptions (0.93, 0.66 to 1.31) (P for heterogeneity=0.002),
      and for use for over 3 years (on average, about 5 years: relative risk v no
      prescription, 2.24, 1.47 to 3.43). Risk of oesophageal cancer did not differ
      significantly by bisphosphonate type, and risk in those with 10 or more
      bisphosphonate prescriptions did not vary by age, sex, smoking, alcohol intake,
      or body mass index; by diagnosis of osteoporosis, fracture, or upper
      gastrointestinal disease; or by prescription of acid suppressants, non-steroidal
      anti-inflammatory drugs, or corticosteroids. Cancers of the stomach and
      colorectum were not associated with prescription of bisphosphonate: relative
      risks for one or more versus no prescriptions were 0.87 (0.64 to 1.19) and 0.87
      (0.77 to 1.00). The specificity of the association for oesophageal cancer argues
      against methodological problems in the selection of cases and controls or in the
      analysis. CONCLUSIONS: The risk of oesophageal cancer increased with 10 or more
      prescriptions for oral bisphosphonates and with prescriptions over about a five
      year period. In Europe and North America, the incidence of oesophageal cancer at
      age 60-79 is typically 1 per 1000 population over five years, and this is
      estimated to increase to about 2 per 1000 with five years' use of oral
      bisphosphonates.

PMID- 20813821
TI  - Oral bisphosphonates and oesophageal cancer.

PMID- 20813822
TI  - Implementation and adoption of nationwide electronic health records in secondary
      care in England: qualitative analysis of interim results from a prospective
      national evaluation.
AB  - OBJECTIVES: To describe and evaluate the implementation and adoption of detailed
      electronic health records in secondary care in England and thereby provide early
      feedback for the ongoing local and national rollout of the NHS Care Records
      Service. DESIGN: A mixed methods, longitudinal, multisite, socio-technical case
      study. SETTING: Five NHS acute hospital and mental health trusts that have been
      the focus of early implementation efforts and at which interim data collection
      and analysis are complete. Data sources and analysis Dataset for the evaluation
      consists of semi-structured interviews, documents and field notes, observations,
      and quantitative data. Qualitative data were analysed thematically with a socio
      technical coding matrix, combined with additional themes that emerged from the
      data. Main results Hospital electronic health record applications are being
      developed and implemented far more slowly than was originally envisioned; the top
      down, standardised approach has needed to evolve to admit more variation and
      greater local choice, which hospital trusts want in order to support local
      activity. Despite considerable delays and frustrations, support for electronic
      health records remains strong, including from NHS clinicians. Political and
      financial factors are now perceived to threaten nationwide implementation of
      electronic health records. Interviewees identified a range of consequences of
      long term, centrally negotiated contracts to deliver the NHS Care Records Service
      in secondary care, particularly as NHS trusts themselves are not party to these
      contracts. These include convoluted communication channels between different
      stakeholders, unrealistic deployment timelines, delays, and applications that
      could not quickly respond to changing national and local NHS priorities. Our data
      suggest support for a "middle-out" approach to implementing hospital electronic
      health records, combining government direction with increased local autonomy, and
      for restricting detailed electronic health record sharing to local health
      communities. CONCLUSIONS: Experiences from the early implementation sites, which
      have received considerable attention, financial investment and support, indicate
      that delivering improved healthcare through nationwide electronic health records
      will be a long, complex, and iterative process requiring flexibility and local
      adaptability both with respect to the systems and the implementation strategy.
      The more tailored, responsive approach that is emerging is becoming better
      aligned with NHS organisations' perceived needs and is, if pursued, likely to
      deliver clinically useful electronic health record systems.

PMID- 20813823
TI  - Choice of fluids for resuscitation in children with severe infection and shock:
      systematic review.
AB  - OBJECTIVE: To systemically review the evidence from clinical trials comparing the
      use of crystalloids and colloids for fluid resuscitation in children with severe
      infection. DATA SOURCES: Medline (1950-2008), PubMed, the Cochrane Library,
      Embase (1980-2008), and reference lists. Eligibility criteria Published studies
      comparing fluid resuscitation with crystalloid or colloidal solutions in severe
      infectious illness in children aged >1 month to <or=12 years. Controlled trials
      and randomised controlled trials were separately selected by two unblinded
      investigators who also independently extracted data. MAIN OUTCOME MEASURES:
      Efficacy in the treatment of shock, mortality, and reported adverse events.
      RESULTS: Nine trials fulfilled criteria, eight of which compared crystalloids
      with colloids. All trials were conducted in settings with poor resources and
      predominantly included patients with malaria or dengue haemorrhagic shock. None
      of the trials had mortality as a primary outcome. Three out of six studies that
      reported at least one death showed better survival in children resuscitated with
      colloids compared with crystalloids (Peto fixed odds ratio ranging from 0.18 (95%
      confidence interval 0.02 to 1.42) to 0.48 (0.06 to 3.99)). Studies contributing
      data on mortality had some methodological limitations so caution is recommended
      when interpreting this finding. Studies were heterogeneous so combined estimates
      were not calculated. The review was limited by inclusion of only published
      studies. CONCLUSIONS: The current evidence on choice of fluids for resuscitation
      in children with infections is weak. While existing trials have provided
      important evidence in malaria and dengue, resuscitation in children with
      paediatric sepsis, for which colloids could theoretically be of benefit, has not
      been studied. The evidence from existing studies is not robust enough to make any
      definitive recommendations over the choice of resuscitation fluid and a
      definitive trial is required to address this.

PMID- 20813824
TI  - Transient loss of consciousness--initial assessment, diagnosis, and specialist
      referral: summary of NICE guidance.

PMID- 20813825
TI  - Choice of fluids for resuscitation in children with severe infection and shock.

PMID- 20813826
TI  - Malaria is on the rise in Pakistan, health workers warn.

PMID- 20813829
TI  - New figures show major increase in alcohol related hospital admissions in
      England.

PMID- 20813832
TI  - Systemic low temperature signaling in Arabidopsis.
AB  - When leaves are exposed to low temperature, sugars accumulate and transcription
      factors in the C-repeat binding factor (CBF) family are expressed, which,
      together with CBF-independent pathways, are known to contribute to the cold
      acclimation process and an increase in freezing tolerance. What is not known,
      however, is whether expression of these cold-regulated genes can be induced
      systemically in response to a localized cold treatment. To address this, pre
      existing, mature leaves of warm-grown Arabidopsis thaliana were exposed to a
      localized cold treatment (near 10  degrees C) whilst conjoined newly developing
      leaves continued only to experience warmer temperatures. In initial experiments
      on wild-type A. thaliana (Col-0) using real-time reverse transcription--PCR (RT
      PCR) we observed that some genes--including CBF genes, certain downstream cold
      responsive (COR) targets and CBF-independent transcription factors--respond to a
      direct 9  degrees C treatment of whole plants. In subsequent experiments, we
      found that the treatment of expanded leaves with temperatures near 10  degrees C
      can induce cold-associated genes in conjoined warm-maintained tissues. CBF1
      showed a particularly strong systemic response, although CBF-independent
      transcription factors also responded. Moreover, the localized cold treatment of
      A. thaliana (C24) plants with a luciferase reporter fused to the promoter region
      of KIN2 indicated that in warm-maintained leaves, KIN2 might respond to a
      systemic signal from remote, directly cold-treated leaves. Collectively, our
      study provides strong evidence that the processes involved in cold acclimation
      are partially mediated by a signal that acts systemically. This has the potential
      to act as an early-warning system to enable developing leaves to cope better with
      the cold environment in which they are growing.

PMID- 20813833
TI  - IFN induces miR-21 through a signal transducer and activator of transcription 3
      dependent pathway as a suppressive negative feedback on IFN-induced apoptosis.
AB  - The microRNA miR-21 is overexpressed in many human cancers, wherein accumulating
      evidence indicates that it functions as an oncogene. Here, we report that the
      cytokine IFN rapidly induces miR-21 expression in human and mouse cells. Signal
      transducer and activator of transcription 3 (STAT3) was implicated in this
      pathway based on the lack of IFN effect on miR-21 expression in prostate cancer
      cells with a deletion in the STAT3 gene. STAT3 ablation abrogated IFN induction
      of miR-21, confirming the important role of STAT3 in regulating miR-21. Chromatin
      immunoprecipitation analysis showed that STAT3 directly bound the miR-21 promoter
      in response to IFN. Experiments in mouse embryo fibroblasts with a genetic
      deletion of the p65 NF-kappaB subunit showed that IFN-induced miR-21 expression
      was also dependent on NF-kappaB. STAT3 silencing blocked both IFN-induced p65
      binding to the miR-21 promoter and p65 nuclear translocation. Thus, IFN-induced
      miR-21 expression is coregulated by STAT3 and NF-kappaB at the level of the miR
      21 promoter. Several cell death regulators were identified as downstream targets
      of miR-21, including PTEN and Akt. Functional experiments in prostate cancer
      cells directly showed that miR-21 plays a critical role in suppressing IFN
      induced apoptosis. Our results identify miR-21 as a novel IFN target gene that
      functions as a key feedback regulator of IFN-induced apoptosis.

PMID- 20813834
TI  - Tetralogy of Fallot with absent pulmonary valve, supracardiac total anomalous
      pulmonary venous connection, and infradiaphragmatic systemic to pulmonary
      collateral artery.

PMID- 20813835
TI  - N termini of apPDE4 isoforms are responsible for targeting the isoforms to
      different cellular membranes.
AB  - Phosphodiesterases (PDEs) are known to play a key role in the
      compartmentalization of cAMP signaling; however, the molecular mechanisms
      underlying intracellular localization of different PDE isoforms are not
      understood. In this study, we have found that each of the supershort, short, and
      long forms of apPDE4 showed distinct localization in the cytoplasm, plasma
      membrane, and both plasma membrane and presynaptic terminals, respectively. The N
      terminal 20 amino acids of the long form of apPDE4 were involved in presynaptic
      terminal targeting by binding to several lipids. In addition, the N terminus of
      the short form of apPDE4 bound to several lipids including phosphoinositols,
      thereby targeting the plasma membrane. Overexpression of the long and the short
      forms, but not the supershort form attenuated 5-HT-induced membrane
      hyperexcitability. Finally, the knockdown of apPDE4s in sensory neurons impaired
      both short-term and long-term facilitation. Thus, these results suggest that
      apPDE4s can participate in the regulation of cAMP signaling through specific
      subcellular localization by means of lipid binding activities.

PMID- 20813836
TI  - Phenylmethimazole blocks palmitate-mediated induction of inflammatory cytokine
      pathways in 3T3L1 adipocytes and RAW 264.7 macrophages.
AB  - Visceral adipocytes and associated macrophages produce and release excessive
      amounts of biologically active inflammatory cytokines via the portal and systemic
      vascular system, which induce insulin resistance in insulin target tissues such
      as fat, liver, and muscle. Free fatty acids (FFAs) absorbed via the portal system
      or released from adipocytes also induce insulin resistance. In this report, we
      show that phenylmethimazole (C10) blocks basal IL6 and leptin production as well
      as basal Socs-3 expression in fully differentiated 3T3L1 cells (3T3L1 adipocytes)
      without affecting insulin-stimulated AKT signaling. In addition, C10 inhibits
      palmitate-induced IL6 and iNos up-regulation in both 3T3L1 adipocytes and RAW
      264.7 macrophages, LPS-induced NF-kappaB and IFN-beta activation in 3T3L1 cells,
      and LPS-induced iNos, Ifn-beta, Il1beta, Cxcl10, and Il6 expression in RAW 264.7
      macrophages. C10 also blocks palmitate-induced Socs-3 up-regulation and insulin
      receptor substrate-1 (IRS-1) serine 307 phosphorylation in 3T3L1 adipocytes.
      Additionally, we show for the first time that although palmitate increases IRS-1
      serine 307 phosphorylation in 3T3L1 adipocytes, AKT serine 473 phosphorylation is
      enhanced, not reduced, by palmitate. These results suggest that through
      inhibition of FFA-mediated signaling in adipocytes and associated macrophages, as
      well as possibly other insulin target cells/tissues (i.e. non-immune cells), C10
      might be efficacious to prevent or reverse cytokine-induced insulin resistance
      seen in obesity-related insulin resistance and type 2 diabetes mellitus.

PMID- 20813837
TI  - Expanding health insurance coverage in vulnerable groups: a systematic review of
      options.
AB  - Vulnerable groups are often not covered by health insurance schemes. Strategies
      to extend coverage in these groups will help to address inequity. We used the
      existing literature to summarize the options for expanding health insurance
      coverage, describe which countries have tried these strategies, and identify and
      describe evaluation studies. We included any report of a policy or strategy to
      expand health insurance coverage and any evaluation and economic modelling
      studies. Vulnerable populations were defined as children, the elderly, women, low
      income individuals, rural population, racial or ethnic minorities, immigrants,
      and those with disability or chronic diseases. Forty-five databases were searched
      for relevant documents. The authors applied inclusion criteria, and extracted
      data using pre-coded forms, on contents of health insurance schemes or
      programmes, and used the framework approach to establish categories. Of the
      21,528 articles screened, 86 documents were finally included. Descriptions about
      the USA dominated (72), with only five from Africa, six from Asia and two from
      South America. We identified six main categories: (1) changing eligibility
      criteria of health insurance; (2) increasing public awareness; (3) making the
      premium more affordable; (4) innovative enrollment strategies; (5) improving
      health care delivery; and (6) improving management and organization of the
      insurance schemes. All six categories were found in the literature about schemes
      in the USA, and schemes often included components from each category. Strategies
      in developing countries were much more limited in their scope. Evaluation studies
      numbered 25, of which the majority were of time series design. All studies found
      that the expansion strategies were effective, as assessed by the author(s). In
      countries expanding coverage, the categories identified from the literature can
      help policy makers consider their options, implement strategies where it is
      common sense to do so and establish appropriate implementation monitoring.

PMID- 20813838
TI  - Percutaneous tracheostomy: a 6 yr prospective evaluation of the single tapered
      dilator technique.
AB  - BACKGROUND: The single tapered dilator (STD) percutaneous dilatational
      tracheostomy (PDT) technique now appears to be the single most common method of
      performing a tracheostomy in the critical care unit (CCU). METHODS: A single
      centre, prospective evaluation of all PDTs performed in an adult mixed surgical
      and medical CCU between November 2003 and October 2009 was done. All procedures
      were undertaken by critical care physicians. A proforma recorded intraoperative
      complications and technical difficulties encountered during the procedure; all
      patients were followed up for a minimum of 3 months for delayed complications.
      RESULTS: A tracheostomy was performed on 589 patients during the study period.
      PDT was attempted in 576 patients and successfully completed in 572. PDT was
      abandoned in four patients due to bleeding, with three of these subsequently
      undergoing surgical tracheostomy (ST). ST was performed in 17 patients.
      Intraoperative technical difficulties were encountered in 149 (26%) cases.
      Sixteen (3%) procedures were deemed as having early complications. A further four
      (0.7%) cases had significant late complications including two tracheo-innominate
      fistulae (TIF). Both TIF patients died as a result of their complications giving
      a mortality directly attributable to PDT of 0.35%. There were no differences with
      respect to the occurrence of complications according to grade of operator.
      CONCLUSIONS: PDT performed by the STD technique is a relatively safe procedure
      with more than 96% of procedures performed without any early or late
      complications. Using this technique, more than 97% of tracheostomies undertaken
      during the study period were performed percutaneously. Further audit at a
      national level is warranted to fully evaluate long-term complications after PDT.

PMID- 20813839
TI  - Lipidation by the host prenyltransferase machinery facilitates membrane
      localization of Legionella pneumophila effector proteins.
AB  - The intracellular human pathogen Legionella pneumophila translocates multiple
      proteins in the host cytosol known as effectors, which subvert host cellular
      processes to create a membrane-bound organelle that supports bacterial
      replication. It was observed that several Legionella effectors encode a
      prototypical eukaryotic prenylation CAAX motif (where C represents a cysteine
      residue and A denotes an aliphatic amino acid). These bacterial motifs mediated
      posttranslational modification of effector proteins resulting in the addition of
      either a farnesyl or geranylgeranyl isoprenyl lipid moiety to the cysteine
      residue of the CAAX tetrapeptide. Lipidation enhanced membrane affinity for most
      Legionella CAAX motif proteins and facilitated the localization of these effector
      proteins to host organelles. Host farnesyltransferase and class I
      geranylgeranyltransferase were both involved in the lipidation of the Legionella
      CAAX motif proteins. Perturbation of the host prenylation machinery during
      infection adversely affected the remodeling of the Legionella-containing vacuole.
      Thus, these data indicate that Legionella utilize the host prenylation machinery
      to facilitate targeting of effector proteins to membrane-bound organelles during
      intracellular infection.

PMID- 20813840
TI  - Tyr-167/Trp-168 in type 1/3 inositol 1,4,5-trisphosphate receptor mediates
      functional coupling between ligand binding and channel opening.
AB  - The N-terminal ~220-amino acid region of the inositol 1,4,5-trisphosphate (IP(3))
      receptor (IP(3)R)/Ca(2+) release channel has been referred to as the
      suppressor/coupling domain because it is required for both IP(3) binding
      suppression and IP(3)-induced channel gating. Measurements of IP(3)-induced
      Ca(2+) fluxes of mutagenized mouse type 1 IP(3)R (IP(3)R1) showed that the
      residues responsible for IP(3) binding suppression in this domain were not
      essential for channel opening. On the other hand, a single amino acid
      substitution of Tyr-167 to alanine completely impaired IP(3)-induced Ca(2+)
      release without reducing the IP(3) binding activity. The corresponding residue in
      type 3 IP(3)R (IP(3)R3), Trp-168, was also critical for channel opening. Limited
      trypsin digestion experiments showed that the trypsin sensitivities of the C
      terminal gatekeeper domain differed markedly between the wild-type channel and
      the Tyr-167 mutant under the optimal conditions for channel opening. These
      results strongly suggest that the Tyr/Trp residue (Tyr-167 in IP(3)R1 and Trp-168
      in IP(3)R3) is critical for the functional coupling between IP(3) binding and
      channel gating by maintaining the structural integrity of the C-terminal
      gatekeeper domain at least under activation gating.

PMID- 20813841
TI  - Time lapse in vivo visualization of developmental stabilization of synaptic
      receptors at neuromuscular junctions.
AB  - The lifetime of nicotinic acetylcholine receptors (AChRs) in neuromuscular
      junctions (NMJs) is increased from <1 day to >1 week during early postnatal
      development. However, the exact timing of AChR stabilization is not known, and
      its correlation to the concurrent embryonic to adult AChR channel conversion, NMJ
      remodeling, and neuromuscular diseases is unclear. Using a novel time lapse in
      vivo imaging technology we show that replacement of the entire receptor
      population of an individual NMJ occurs end plate-specifically within hours. This
      makes it possible to follow directly in live animals changing stabilities of end
      plate receptors. In three different, genetically modified mouse models we
      demonstrate that the metabolic half-life values of synaptic AChRs increase from a
      few hours to several days after postnatal day 6. Developmental stabilization is
      independent of receptor subtype and apparently regulated by an intrinsic muscle
      specific maturation program. Myosin Va, an F-actin-dependent motor protein, is
      also accumulated synaptically during postnatal development and thus could mediate
      the stabilization of end plate AChR.

PMID- 20813842
TI  - Activation of the transcription factor FosB/activating protein-1 (AP-1) is a
      prominent downstream signal of the extracellular nucleotide receptor P2RX7 in
      monocytic and osteoblastic cells.
AB  - Activation of the ionotropic P2RX7 nucleotide receptor by extracellular ATP has
      been implicated in modulating inflammatory disease progression. Continuous
      exposure of P2RX7 to ligand can result in apoptosis in many cell types, including
      monocytic cells, whereas transient activation of P2RX7 is linked to inflammatory
      mediator production and the promotion of cell growth. Given the rapid hydrolysis
      of ATP in the circulation and interstitial space, transient activation of P2RX7
      appears critically important for its action, yet its effects on gene expression
      are unclear. The present study demonstrates that short-term stimulation of human
      and mouse monocytic cells as well as mouse osteoblasts with P2RX7 agonists
      substantially induces the expression of several activating protein-1 (AP-1)
      members, particularly FosB. The potent activation of FosB after P2RX7 stimulation
      is especially noteworthy considering that little is known concerning the role of
      FosB in immunological regulation. Interestingly, the magnitude of FosB activation
      induced by P2RX7 stimulation appears greater than that observed with other known
      inducers of FosB expression. In addition, we have identified a previously
      unrecognized role for FosB in osteoblasts with respect to nucleotide-induced
      expression of cyclooxygenase-2 (COX-2), which is the rate-limiting enzyme in
      prostaglandin biosynthesis from arachidonic acid and is critical for osteoblastic
      differentiation and immune behavior. The present studies are the first to link
      P2RX7 action to FosB/AP-1 regulation in multiple cell types, including a role in
      nucleotide-induced COX-2 expression, and support a role for FosB in the control
      of immune and osteogenic function by P2RX7.

PMID- 20813843
TI  - A processed multidomain mycoplasma hyopneumoniae adhesin binds fibronectin,
      plasminogen, and swine respiratory cilia.
AB  - Porcine enzootic pneumonia is a chronic respiratory disease that affects swine.
      The etiological agent of the disease, Mycoplasma hyopneumoniae, is a bacterium
      that adheres to cilia of the swine respiratory tract, resulting in loss of cilia
      and epithelial cell damage. A M. hyopneumoniae protein P116, encoded by mhp108,
      was investigated as a potential adhesin. Examination of P116 expression using
      proteomic analyses observed P116 as a full-length protein and also as fragments,
      ranging from 17 to 70 kDa in size. A variety of pathogenic bacterial species have
      been shown to bind the extracellular matrix component fibronectin as an adherence
      mechanism. M. hyopneumoniae cells were found to bind fibronectin in a dose
      dependent and saturable manner. Surface plasmon resonance was used to show that a
      recombinant C-terminal domain of P116 bound fibronectin at physiologically
      relevant concentrations (K(D) 24 +/- 6 nm). Plasmin(ogen)-binding proteins are
      also expressed by many bacterial pathogens, facilitating extracellular matrix
      degradation. M. hyopneumoniae cells were found to also bind plasminogen in a dose
      dependent and saturable manner; the C-terminal domain of P116 binds to
      plasminogen (K(D) 44 +/- 5 nm). Plasminogen binding was abolished when the C
      terminal lysine of P116 was deleted, implicating this residue as part of the
      plasminogen binding site. P116 fragments adhere to the PK15 porcine kidney
      epithelial-like cell line and swine respiratory cilia. Collectively these data
      suggest that P116 is an important adhesin and virulence factor of M.
      hyopneumoniae.

PMID- 20813844
TI  - Homotypic cell to cell cross-talk among human natural killer cells reveals
      differential and overlapping roles of 2B4 and CD2.
AB  - Human natural killer (NK) cells express an abundant level of 2B4 and CD2 on their
      surface. Their counter-receptors, CD48 and CD58, are also expressed on the NK
      cell surface, raising a question about the functional consequences of potential
      2B4/CD48 and CD2/CD58 interactions. Using blocking antibodies specific to each
      receptor, we demonstrated that both 2B4/CD48 and CD2/CD58 interactions were
      essential for the development of NK effector functions: cytotoxicity and cytokine
      secretion. However, only 2B4/CD48, but not CD2/CD58, interactions were shown to
      be critical for the optimal NK cell proliferation in response to interleukin (IL)
      2. IL-2-activated NK cells cultured in the absence of 2B4/CD48 or CD2/CD58
      interactions were severely impaired for their ability to induce intracellular
      calcium mobilization and subsequent ERK activation upon tumor target exposure,
      suggesting that the early signaling pathway of NK receptors leading to impaired
      cytolysis and interferon (IFN)-gamma secretion was inhibited. Nevertheless, these
      defects did not fully account for the reduced proliferation of NK cells in the
      absence of 2B4/CD48 interactions, because anti-CD2 or anti-CD58 monoclonal
      antibody (mAb)-treated NK cells, showing defective signaling and effector
      functions, displayed normal proliferation upon IL-2 stimulation. These results
      propose the signaling divergence between pathways leading to cell proliferation
      and cytotoxicity/cytokine release, which can be differentially regulated by 2B4
      and CD2 during IL-2-driven NK cell activation. Collectively, these results reveal
      the importance of homotypic NK-to-NK cell cross-talk through 2B4/CD48 and
      CD2/CD58 pairs and further present their differential and overlapping roles in
      human NK cells.

PMID- 20813845
TI  - Myc-dependent mitochondrial generation of acetyl-CoA contributes to fatty acid
      biosynthesis and histone acetylation during cell cycle entry.
AB  - Cell reprogramming from a quiescent to proliferative state requires coordinate
      activation of multiple -omic networks. These networks activate histones, increase
      cellular bioenergetics and the synthesis of macromolecules required for cell
      proliferation. However, mechanisms that coordinate the regulation of these
      interconnected networks are not fully understood. The oncogene c-Myc (Myc)
      activates cellular metabolism and global chromatin remodeling. Here we tested for
      an interconnection between Myc regulation of metabolism and acetylation of
      histones. Using [(13)C(6)]glucose and a combination of GC/MS and LC/ESI tandem
      mass spectrometry, we determined the fractional incorporation of (13)C-labeled 2
      carbon fragments into the fatty acid palmitate, and acetyl-lysines at the N
      terminal tail of histone H4 in myc(-/-) and myc(+/+) Rat1A fibroblasts. Our data
      demonstrate that Myc increases mitochondrial synthesis of acetyl-CoA, as the de
      novo synthesis of (13)C-labeled palmitate was increased 2-fold in Myc-expressing
      cells. Additionally, Myc induced a forty percent increase in (13)C-labeled acetyl
      CoA on H4-K16. This is linked to the capacity of Myc to increase mitochondrial
      production of acetyl-CoA, as we show that mitochondria provide 50% of the acetyl
      groups on H4-K16. These data point to a key role for Myc in directing the
      interconnection of -omic networks, and in particular, epigenetic modification of
      proteins in response to proliferative signals.

PMID- 20813846
TI  - Functional surfaces on the actin-binding protein coronin revealed by systematic
      mutagenesis.
AB  - Coronin is a conserved actin-binding protein that co-functions with ADF/cofilin
      and Arp2/3 complex to govern cellular actin dynamics. Despite emerging roles for
      coronin in a range of physiological processes and disease states, a detailed
      understanding of the molecular interactions of coronin with actin and other
      binding partners has been lacking. Here, we performed a systematic mutational
      analysis of surfaces on the yeast coronin beta-propeller domain, which binds to F
      actin and is conserved in all coronin family members. We generated 21 mutant
      alleles and analyzed their biochemical effects on actin binding and ADF/cofilin
      activity. Conserved actin-binding residues mapped to a discrete ridge stretching
      across one side of the beta-propeller. Mutants defective in actin binding showed
      loss of synergy with ADF/cofilin in severing filaments, diminished localization
      to actin structures in vivo, and loss of coronin overexpression growth defects.
      In addition, one allele showed normal actin binding but impaired functional
      interactions with ADF/cofilin. Another allele showed normal actin binding but
      failed to cause coronin overexpression defects. Together, these results indicate
      that actin binding is critical for many of the biochemical and cellular functions
      of coronin and that the beta-propeller domain mediates additional functional
      interactions with ADF/cofilin and possibly other ligands. Conservation of the
      actin-binding surfaces across distant species and in all three major classes of
      coronin isoforms suggests that the nature of the coronin-actin association may be
      similar in other family members.

PMID- 20813849
TI  - Polymicrobial necrotizing fasciitis involving enterobacteria producing CTX-M-15
      extended-spectrum beta-lactamases.
AB  - Necrotizing fasciitis due to multiple Gram-negative organisms in a Nigerian
      patient is described. Morganella morganii and Citrobacter freundii carrying the
      CTX-M-15 extended-spectrum beta-lactamase gene were isolated, highlighting the
      emergence of this beta-lactamase in Western Africa and its successful spread
      amongst a wider range of members of the Enterobacteriaceae.

PMID- 20813847
TI  - Proliferating cell nuclear antigen (PCNA) is required for cell cycle-regulated
      silent chromatin on replicated and nonreplicated genes.
AB  - In Saccharomyces cerevisiae, silent chromatin is formed at HMR upon the passage
      through S phase, yet neither the initiation of DNA replication at silencers nor
      the passage of a replication fork through HMR is required for silencing.
      Paradoxically, mutations in the DNA replication processivity factor, POL30,
      disrupt silencing despite this lack of requirement for DNA replication in the
      establishment of silencing. We tested whether pol30 mutants could establish
      silencing at either replicated or non-replicated HMR loci during S phase and
      found that pol30 mutants were defective in establishing silencing at HMR
      regardless of its replication status. Although previous studies tie the silencing
      defect of pol30 mutants to the chromatin assembly factors Asf1p and CAF-1, we
      found pol30 mutants did not exhibit a gross defect in packaging HMR into
      chromatin. Rather, the pol30 mutants exhibited defects in histone modifications
      linked to ASF1 and CAF-1-dependent pathways, including SAS-I- and Rtt109p
      dependent acetylation events at H4-K16 and H3-K9 (plus H3-K56; Miller, A., Yang,
      B., Foster, T., and Kirchmaier, A. L. (2008) Genetics 179, 793-809). Additional
      experiments using FLIM-FRET revealed that Pol30p interacted with SAS-I and
      Rtt109p in the nuclei of living cells. However, these interactions were disrupted
      in pol30 mutants with defects linked to ASF1- and CAF-1-dependent pathways.
      Together, these results imply that Pol30p affects epigenetic processes by
      influencing the composition of chromosomal histone modifications.

PMID- 20813850
TI  - Two Japanese Corynebacterium ulcerans isolates from the same hospital: ribotype,
      toxigenicity and serum antitoxin titre.
AB  - Two toxigenic Corynebacterium ulcerans isolates recovered from pharyngeal swabs
      of two patients from the same hospital in Japan during 2001-2002 were
      characterized by PFGE and ribotyping. Toxin production in different culture media
      was examined and serological analysis of patient sera was performed. The two
      isolates could not be distinguished by PFGE; however, their ribotypes were
      distinguishable. One of the isolates could represent a novel ribotype. Analysis
      of toxin production in different culture media demonstrated that the two isolates
      produced varying amounts of the diphtheria toxin. Serological analysis showed a
      greater than sevenfold increase in the serum antitoxin titre during the course of
      infection in one patient.

PMID- 20813848
TI  - Plasma vitamins B2, B6, and B12, and related genetic variants as predictors of
      colorectal cancer risk.
AB  - BACKGROUND: B-vitamins are essential for one-carbon metabolism and have been
      linked to colorectal cancer. Although associations with folate have frequently
      been studied, studies on other plasma vitamins B2, B6, and B12 and colorectal
      cancer are scarce or inconclusive. METHODS: We carried out a nested case-control
      study within the European Prospective Investigation into Cancer and Nutrition,
      including 1,365 incident colorectal cancer cases and 2,319 controls matched for
      study center, age, and sex. We measured the sum of B2 species riboflavin and
      flavin mononucleotide, and the sum of B6 species pyridoxal 5'-phosphate,
      pyridoxal, and 4-pyridoxic acid as indicators for vitamin B2 and B6 status, as
      well as vitamin B12 in plasma samples collected at baseline. In addition, we
      determined eight polymorphisms related to one-carbon metabolism. Relative risks
      for colorectal cancer were estimated using conditional logistic regression,
      adjusted for smoking, education, physical activity, body mass index, alcohol
      consumption, and intakes of fiber and red and processed meat. RESULTS: The
      relative risks comparing highest to lowest quintile were 0.71 [95% confidence
      interval (95% CI), 0.56-0.91; P(trend) = 0.02] for vitamin B2, 0.68 (95% CI, 0.53
      0.87; P(trend) <0.001) for vitamin B6, and 1.02 (95% CI, 0.80-1.29; P(trend) =
      0.19) for vitamin B12. The associations for vitamin B6 were stronger in males who
      consumed >=30 g alcohol/day. The polymorphisms were not associated with
      colorectal cancer. CONCLUSIONS: Higher plasma concentrations of vitamins B2 and
      B6 are associated with a lower colorectal cancer risk. IMPACT: This European
      population-based study is the first to indicate that vitamin B2 is inversely
      associated with colorectal cancer, and is in agreement with previously suggested
      inverse associations of vitamin B6 with colorectal cancer.

PMID- 20813851
TI  - Rapid differentiation of Staphylococcus aureus, Staphylococcus epidermidis and
      other coagulase-negative staphylococci and meticillin susceptibility testing
      directly from growth-positive blood cultures by multiplex real-time PCR.
AB  - This study evaluated a multiplex real-time PCR method specific for the mecA, femA
      SA and femA-SE genes for rapid identification of Staphylococcus aureus,
      Staphylococcus epidermidis and non-S. epidermidis coagulase-negative
      staphylococci (CoNS), and meticillin susceptibility testing directly in positive
      blood cultures that grew Gram-positive cocci in clusters. A total of 100 positive
      blood cultures produced: 39 S. aureus [12 meticillin-resistant S. aureus (MRSA),
      31% of all the S. aureus]; 30 S. epidermidis (56.6% of the CoNS), 8
      Staphylococcus capitis (15.1%), 3 Staphylococcus saprophyticus (5.7%), 4
      Staphylococcus hominis (7.5%), 3 Staphylococcus haemolyticus (5.7%), 2
      Staphylococcus warneri (3.8%), 1 Staphylococcus cohnii (1.9%) and 2 unidentified
      Staphylococcus spp. (3.8%); and 1 Micrococcus luteus in pure culture. Two blood
      cultures had no growth on subculture and five blood cultures grew mixed CoNS. For
      the 95 blood cultures with pure growth or no growth on subculture, there was very
      good agreement between real-time PCR and the BD Phoenix identification system for
      staphylococcal species categorization in S. aureus, S. epidermidis and non-S.
      epidermidis CoNS and meticillin-resistance determination (Cohen's unweighted
      kappa coefficient kappa=0.882). All MRSA and meticillin-susceptible S. aureus
      were correctly identified by mecA amplification. PCR amplification of mecA was
      more sensitive for direct detection of meticillin-resistant CoNS in positive
      blood cultures than testing with the BD Phoenix system. There were no major
      errors when identifying staphylococcal isolates and their meticillin
      susceptibility within 2.5 h. Further studies are needed to evaluate the clinical
      benefit of using such a rapid test on the consumption of glycopeptide antibiotics
      and the alteration of empiric therapy in the situation of positive blood cultures
      growing staphylococci, and the respective clinical outcomes.

PMID- 20813852
TI  - Molecular characterization of antimicrobial resistance in non-typhoidal
      salmonellae associated with systemic manifestations from India.
AB  - Extended-spectrum cephalosporins and fluoroquinolones are essential
      antimicrobials for treating invasive salmonellosis, although emerging resistance
      to these antimicrobials is of growing concern, especially in India. Therefore, a
      study was conducted to characterize the antimicrobial susceptibility phenotypes,
      types of extended-spectrum beta-lactamase (ESBL) gene plasmids and serological
      relationships of 21 non-typhoidal Salmonella isolates from patients who attended
      three different hospitals in India from 2006 to 2008. The isolates were cultured
      from stool, blood and cerebrospinal fluid samples obtained from patients
      presenting with diarrhoea and accompanying systemic manifestations such as fever,
      vomiting and meningism. Non-typhoidal Salmonella isolates were investigated using
      serotyping and antimicrobial susceptibility testing. PCR screening was also
      performed to detect the beta-lactamase, qnr and aac(6')-Ib-cr genes and class 1
      integrons. Sequencing for quinolone resistance mutations and plasmid replicon
      typing were also performed. An antimicrobial resistance microarray was used for
      preliminary screening and identification of bla(TEM) and bla(SHV) genes, and
      phenotypic testing for the presence of efflux pumps was also performed. Ten out
      of 21 isolates (48%) possessed the extended-spectrum cephalosporin resistance
      phenotype, with PCR amplification and sequencing revealing that isolates
      possessed TEM-1, SHV-12, DHA-1, OXA-1-like and CTX-M-15 ESBL genes. FII(s)
      plasmid replicons were detected in seven isolates (33%). The involvement of
      efflux pumps was detected in four isolates (19%) resistant to ciprofloxacin. It
      was concluded that SHV-12-carrying Salmonella serotype Agona may play an
      important role in ESBL-mediated resistance in non-typhoidal salmonellae in India.
      The very high percentage (48%) of ESBL-producing non-typhoidal salmonellae
      isolated from these patients represents a real and immediate challenge to the
      effective antimicrobial therapy of Salmonella infections associated with systemic
      manifestations. Continued surveillance for the presence of ESBL-producing (non
      typhoidal) salmonellae in India is essential.

PMID- 20813853
TI  - Health benefits in 2010: premiums rise modestly, workers pay more toward
      coverage.
AB  - Our annual analysis of health benefits contains findings from interviews of 2,046
      public and private employers surveyed during January-May 2010. Average annual
      premiums in 2010 were $5,049 for single coverage and $13,770 for family coverage-
      up 5 percent and 3 percent from 2009, respectively. Workers paid more toward
      premiums in 2010, and more workers are in consumer-directed plans and plans with
      high deductibles than in 2009. Thirty percent of firms reported that they reduced
      the scope of benefits or increased cost sharing because of the recession.
      Surprisingly, the percentage of firms offering health benefits in 2010 increased
      to 69 percent, up from 60 percent in 2009. The change was largely driven by a
      thirteen-percentage-point increase in the number of firms with three to nine
      workers that offered benefits (up from 46 percent in 2009 to 59 percent in 2010).
      The reason for this increase is unclear.

PMID- 20813854
TI  - Prognostic indicators of renal disease progression in adults with Fabry disease:
      natural history data from the Fabry Registry.
AB  - BACKGROUND AND OBJECTIVES: These analyses were designed to characterize renal
      disease progression in untreated adults with Fabry disease. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Data from the Fabry Registry for 462 untreated
      adults (121 men and 341 women) who had at least two estimated GFR (eGFR) values
      over a span of >=12 months before starting enzyme replacement therapy were
      included. RESULTS: Most men (86 of 121, 71%) had more rapid loss of kidney
      function than the normal adult population (loss of eGFR > -1 ml/min per 1.73 m(2)
      per year), whereas fewer women (133 of 341, 39%) had rapid loss of kidney
      function. Patients with rapid progression had significantly higher mean averaged
      urinary protein to urinary creatinine ratios (UP/Cr) than patients with slower
      progression (1.5 versus 0.2 for men; 1.4 versus 0.5 for women; P < 0.0001).
      Patients were grouped into quartiles based on averaged UP/Cr; renal function in
      men declined more rapidly with higher UP/Cr, with the steepest declines observed
      in men with UP/Cr > 1.5 (mean eGFR slope, -5.6 ml/min per 1.73 m(2) per year; n =
      30). eGFR slope declined more slowly in women, with the steepest declines
      observed in women with UP/Cr > 1.2 (mean eGFR slope, -1.3 ml/min per 1.73 m(2)
      per year; n = 85). Regression models of eGFR slope indicated that UP/Cr is the
      most important indicator of renal disease progression in adult Fabry patients. In
      women, lower baseline eGFR and age were also associated with renal disease
      progression. Women who had clinical events had more rapid loss of kidney
      function. CONCLUSIONS: Urinary protein excretion is strongly associated with
      renal disease progression in men and women with Fabry disease.

PMID- 20813855
TI  - Association between clinical risk factors and progression of chronic kidney
      disease in children.
AB  - BACKGROUND AND OBJECTIVES: Children with chronic kidney disease (CKD) have an
      increased risk of progression to ESRD. There is a need to identify treatments to
      slow the progression of CKD, yet there are limited data regarding clinical risk
      factors that may be suitable targets to slow progression. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: We performed a retrospective cohort study using the
      North American Pediatric Renal Trials and Cooperative Studies CKD database. There
      were 4166 pediatric subjects with CKD stages II to IV. Disease progression was
      defined as a GFR on follow-up of <15 ml/min per 1.73 m(2) or termination in the
      registry because of dialysis or transplantation. We used Kaplan-Meier and Cox
      proportional hazards methods to describe progression rates and determine factors
      associated with CKD progression. RESULTS: In the univariate analysis, CKD
      progression was associated with age, gender, race, primary disease, CKD stage,
      registration year, hematocrit, albumin, corrected calcium, corrected phosphorus,
      and use of certain medications. Factors that remained significant in the
      multivariate analysis were age, primary disease, CKD stage, registration year,
      hypertension, corrected phosphorus, corrected calcium, albumin, hematocrit, and
      medication proxies for anemia and short stature. CONCLUSIONS: There are multiple
      risk factors associated with disease progression in the pediatric CKD population.
      Factors that may be amenable to intervention include anemia, hypoalbuminemia,
      hyperphosphatemia, hypocalcemia, hypertension, and short stature. Because of the
      retrospective nature of our study, confirmation of our results from ongoing
      prospective studies is warranted before recommending prospective interventional
      trials.

PMID- 20813856
TI  - An emerging population: kidney transplant candidates who are placed on the
      waiting list after liver, heart, and lung transplantation.
AB  - BACKGROUND AND OBJECTIVES: ESRD has an adverse impact on patients who have had
      previous nonrenal solid-organ transplants (NRTxs; liver, heart, lung) and may be
      referred for a kidney transplant (KTx). DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Using Scientific Registry of Transplant Recipients data for all KTx
      candidates who had NRTx and were listed between 1995 and 2008, incidence of NRTx
      listings were compared with trends in KTx without NRTX. The efficacy of kidney
      transplantation relative to dialysis was measured in time-dependent Cox models
      that incorporated candidates with the applicable previous organ transplant as a
      reference group. RESULTS: Overall, 4904 NRTx candidates were listed during the
      study period, growing from <1% of candidates before 1995 to 3.3% in 2008. A total
      of 38% of NRTx candidates were listed preemptively versus 21% of other
      candidates. NRTx candidates had dramatically shorter half-lives (<= 4 years)
      after listing compared with previous KTx recipients (9.2 years). KTx demonstrated
      a survival advantage for each type of NRTx candidate relative to maintenance
      dialysis. Listing for expanded-criteria donor kidneys averaged 47% and did not
      differ significantly by previous transplant category. CONCLUSIONS: KTx candidates
      who are placed on the waiting list after NRTx constitute a significant and more
      rapidly growing cohort compared with the general KTx candidate population. NRTx
      candidates are frequently listed preemptively but have rapid decline once placed
      on the waiting list. Targeted use of expanded-criteria donor and living-donor
      transplants in the NRTx population may be particularly important given their high
      mortality on the waiting list.

PMID- 20813857
TI  - Pathological significance of a panel of urinary biomarkers in patients with drug
      induced tubulointerstitial nephritis.
AB  - BACKGROUND AND OBJECTIVES: Although a renal biopsy is indispensable for depicting
      the severity of pathologic lesions in drug-induced tubulointerstitial nephritis
      (DTIN), it is not acceptable in some cases and cannot be performed serially
      because of its invasive nature. Therefore, the discovery of noninvasive markers
      that are closely related to the pathology of DTIN is of great value. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: In this study, the urinary levels of
      monocyte chemotactic peptide-1 (MCP-1), neutrophil gelatinase-associated
      lipocalin (NGAL), N-acetyl-beta-d-glucosaminidase, and alpha1-microglobulin were
      measured in 40 DTIN subjects, and the performances of these parameters for
      distinguishing different pathologic lesions were compared. RESULTS: Linear
      correlation and receiver operating characteristic curve analyses showed that
      urinary MCP-1 levels were able to identify serious interstitial edema and
      inflammatory infiltration with greater accuracy than the other biomarkers (r =
      0.501, P < 0.001 and r = 0.768, P < 0.001, respectively), whereas urinary NGAL
      levels showed the highest correlation coefficient with tubular atrophy (r =
      0.692, P < 0.001). CONCLUSIONS: These results suggest that these biomarker levels
      were higher in patients with DTIN than in controls. Urinary MCP-1 levels
      correlated and were predictive of the gradated severity of acute lesions in DTIN,
      whereas the roles of NGAL and alpha1-microglobulin in chronic alterations require
      further study.

PMID- 20813858
TI  - Multidisciplinary evaluation for severity of hazards applied to hemodialysis
      devices: an original risk analysis method.
AB  - BACKGROUND AND OBJECTIVES: Risk analysis for medical devices is a crucial process
      to grant adequate levels of safety. Identification of device exposure-related
      hazards is one of the main objectives. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Hazard analysis for hemodialysis devices has been performed by a
      multidisciplinary team involving engineers and clinical experts. A potential harm
      list was identified from clinical and technical experience, postproduction
      information, and literature. Various hazardous situations (circumstances when the
      use of the dialysis device may lead to described harms) were described. Such
      hazardous situations were correlated to the extent of the deviation of a specific
      device parameter from expected ranges. The clinical severity that was relevant to
      any specific harm was categorized for each hazardous situation using a
      descriptive and numerical scale with five levels (from negligible [i.e.,
      discomfort only] to catastrophic [i.e., potentially lethal]). RESULTS: Harms in
      which the deviation of a parameter strictly coincides with the clinically
      measured effect on the patient are defined as "direct." Otherwise, when another
      clinical parameter must be involved to quantify severity, the related harm is
      considered "indirect." Two complete examples of multidisciplinary evaluation for
      severity of hazards (MESH) are given for a direct harm (air embolism) and for an
      indirect harm (hypothermia). For other harms, the maximum value of severity
      involved is provided. CONCLUSIONS: MESH represents a possible example of risk
      management for dialysis equipment in which, although the manufacturer is directly
      responsible, a multidisciplinary task force may contribute to a better link
      between engineering and clinical perspectives.

PMID- 20813859
TI  - Modified C-reactive protein might be a target autoantigen of TINU syndrome.
AB  - BACKGROUND AND OBJECTIVES: The cross-reactive antigen(s) of tubulointerstitial
      nephritis and uveitis (TINU) syndrome from renal tubulointerstitia and ocular
      tissue remain unidentified. The authors' recent study demonstrated that the
      presence of serum IgG autoantibodies against modified C-reactive protein (mCRP)
      was closely associated with the intensity of tubulointerstitial lesions in lupus
      nephritis. The study presented here investigates the possible role of IgG
      autoantibodies against mCRP in patients with TINU syndrome. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: mCRP autoantibodies were screened by ELISA with
      purified human C-reactive protein in 9 patients with TINU syndrome, 11 with drug
      associated acute interstitial nephritis, 20 with IgA nephropathy, 19 with minimal
      change disease, 20 with ANCA-associated vasculitis, 6 with Sjogren's syndrome,
      and 12 with amyloidosis. mCRP expression was analyzed by immunohistochemistry in
      renal biopsy specimens from the 9 patients with TINU syndrome and 40 from disease
      controls. Frozen normal human kidney and iris were used to demonstrate co
      localization of human IgG and mCRP from patients with TINU syndrome with laser
      scanning confocal microscopy. RESULTS: The mCRP autoantibodies were detected in
      all nine patients with TINU syndrome, significantly higher than that of those
      with disease controls (P < 0.05). The renal histologic score of mCRP in TINU
      syndrome was significantly higher than that in disease controls (P < 0.05). The
      staining of mCRP and human IgG were co-localized in renal and ocular tissues.
      CONCLUSIONS: It is concluded that mCRP might be a target autoantigen in TINU
      syndrome.

PMID- 20813860
TI  - Prevalence of CKD in northeastern Italy: results of the INCIPE study and
      comparison with NHANES.
AB  - BACKGROUND AND OBJECTIVES: Sufficiently powered studies to investigate the CKD
      prevalence are few and do not cover southern Europe. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: For the INCIPE study, 6200 Caucasian patients >=40
      years old were randomly selected in northeastern Italy in 2006. Laboratory
      determinations were centralized. The albumin to creatinine ratio in urine and
      estimated GFR from calibrated creatinine (SCr) were determined. A comparison with
      2001 through 2006 NHANES surveys was performed. RESULTS: Prevalence of CKD was
      13.2% in northeastern (NE) Italy (age and gender standardized to the U.S. 2007
      Caucasian population). Prevalence of CKD in U.S. Caucasians is higher (20.3%),
      the major difference being in CKD 3. Risk factors for CKD are more prevalent in
      the United States than in Italy. With use of CKD 3a and 3b stages, CKD prevalence
      decreased in NE Italy (8.5%) and in the United States (12.8%). CONCLUSIONS: The
      prevalence of CKD is high in NE Italy, but lower than that in the United States.
      A large part of the difference in CKD prevalence in NE Italy versus that in the
      United States is due to the different prevalence of CKD 3. The higher prevalence
      of a number of renal risk factors in persons from the United States explains in
      part the different dimensions of the CKD problem in the two populations.

PMID- 20813861
TI  - Quality, quantity and harmony: the DataSHaPER approach to integrating data across
      bioclinical studies.
AB  - BACKGROUND: Vast sample sizes are often essential in the quest to disentangle the
      complex interplay of the genetic, lifestyle, environmental and social factors
      that determine the aetiology and progression of chronic diseases. The pooling of
      information between studies is therefore of central importance to contemporary
      bioscience. However, there are many technical, ethico-legal and scientific
      challenges to be overcome if an effective, valid, pooled analysis is to be
      achieved. Perhaps most critically, any data that are to be analysed in this way
      must be adequately 'harmonized'. This implies that the collection and recording
      of information and data must be done in a manner that is sufficiently similar in
      the different studies to allow valid synthesis to take place. METHODS: This
      conceptual article describes the origins, purpose and scientific foundations of
      the DataSHaPER (DataSchema and Harmonization Platform for Epidemiological
      Research; http://www.datashaper.org), which has been created by a
      multidisciplinary consortium of experts that was pulled together and coordinated
      by three international organizations: P3G (Public Population Project in
      Genomics), PHOEBE (Promoting Harmonization of Epidemiological Biobanks in Europe)
      and CPT (Canadian Partnership for Tomorrow Project). RESULTS: The DataSHaPER
      provides a flexible, structured approach to the harmonization and pooling of
      information between studies. Its two primary components, the 'DataSchema' and
      'Harmonization Platforms', together support the preparation of effective data
      collection protocols and provide a central reference to facilitate harmonization.
      The DataSHaPER supports both 'prospective' and 'retrospective' harmonization.
      CONCLUSION: It is hoped that this article will encourage readers to investigate
      the project further: the more the research groups and studies are actively
      involved, the more effective the DataSHaPER programme will ultimately be.

PMID- 20813862
TI  - Power and instrument strength requirements for Mendelian randomization studies
      using multiple genetic variants.
AB  - BACKGROUND: Mendelian Randomization (MR) studies assess the causality of an
      exposure-disease association using genetic determinants [i.e. instrumental
      variables (IVs)] of the exposure. Power and IV strength requirements for MR
      studies using multiple genetic variants have not been explored. METHODS: We
      simulated cohort data sets consisting of a normally distributed disease trait, a
      normally distributed exposure, which affects this trait and a biallelic genetic
      variant that affects the exposure. We estimated power to detect an effect of
      exposure on disease for varying allele frequencies, effect sizes and samples
      sizes (using two-stage least squares regression on 10,000 data sets-Stage 1 is a
      regression of exposure on the variant. Stage 2 is a regression of disease on the
      fitted exposure). Similar analyses were conducted using multiple genetic variants
      (5, 10, 20) as independent or combined IVs. We assessed IV strength using the
      first-stage F statistic. RESULTS: Simulations of realistic scenarios indicate
      that MR studies will require large (n > 1000), often very large (n > 10,000),
      sample sizes. In many cases, so-called 'weak IV' problems arise when using
      multiple variants as independent IVs (even with as few as five), resulting in
      biased effect estimates. Combining genetic factors into fewer IVs results in
      modest power decreases, but alleviates weak IV problems. Ideal methods for
      combining genetic factors depend upon knowledge of the genetic architecture
      underlying the exposure. CONCLUSIONS: The feasibility of well-powered, unbiased
      MR studies will depend upon the amount of variance in the exposure that can be
      explained by known genetic factors and the 'strength' of the IV set derived from
      these genetic factors.

PMID- 20813863
TI  - Cohort profile: the Amsterdam Born Children and their Development (ABCD) study.

PMID- 20813864
TI  - Emetine promotes von Hippel-Lindau-independent degradation of hypoxia-inducible
      factor-2alpha in clear cell renal carcinoma.
AB  - Inactivating mutations of the von Hippel-Lindau (VHL) tumor suppressor gene are
      associated with inherited VHL syndrome, which is characterized by susceptibility
      to a variety of neoplasms, including central nervous system hemangioblastoma and
      clear cell renal cell carcinoma (CCRCC). Mutations in the VHL gene are also found
      in the majority of sporadic clear cell renal carcinoma, the most common malignant
      neoplasm of the human kidney. Inactivation of VHL ubiquitin ligase is associated
      with normoxic stabilization of hypoxia-inducible factor-1alpha and 2-alpha (HIF
      1alpha and HIF-2alpha), transcriptional regulators of tumor angiogenesis,
      invasion, survival, and glucose utilization. HIF-2alpha has been particularly
      implicated in the development of CCRCC. Although several inhibitors of HIF-1alpha
      have been described, these drugs typically have a minimal affect on HIF-2alpha.
      786-O is a VHL-deficient CCRCC cell line that constitutively expresses only HIF
      2alpha and is therefore suitable for the screening of novel HIF-2alpha
      inhibitors. Using this cell line, we have identified emetine as a specific
      inhibitor of HIF-2alpha protein stability and transcriptional activity. Without
      altering HIF-2alpha mRNA level, emetine rapidly and dramatically down-regulated
      HIF-2alpha protein expression in 786-O cells. HIF-2alpha down-regulation was
      accompanied by HIF-2alpha ubiquitination and was reversed by proteasome
      inhibition. Emetine-induced HIF-2alpha down-regulation was confirmed in three
      additional VHL-renal cancer cell lines, was insensitive to the prolyl hydroxylase
      inhibitor dimethyloxaloyl glycine, and did not require neural precursor cell
      expressed developmentally down-regulated-8, suggesting that emetine accesses a
      previously undescribed cullin-independent proteasome degradation pathway for HIF
      2alpha. These data support the use of emetine or structurally related compounds
      as useful leads for the identification of novel HIF-2alpha inhibitors.

PMID- 20813865
TI  - SPAK-knockout mice manifest Gitelman syndrome and impaired vasoconstriction.
AB  - Polymorphisms in the gene encoding sterile 20/SPS1-related proline/alanine-rich
      kinase (SPAK) associate with hypertension susceptibility in humans. SPAK
      interacts with WNK kinases to regulate the Na(+)-K(+)-2Cl(-) and Na(+)-Cl(-) co
      transporters [collectively, N(K)CC]. Mutations in WNK1/4 and N(K)CC can cause
      changes in BP and dyskalemia in humans, but the physiologic role of SPAK in vivo
      is unknown. We generated and analyzed SPAK-null mice by targeting disruption of
      exons 9 and 10 of SPAK. Compared with SPAK(+/+) littermates, SPAK(+/-) mice
      exhibited hypotension without significant electrolyte abnormalities, and SPAK(-/
      ) mice not only exhibited hypotension but also recapitulated Gitelman syndrome
      with hypokalemia, hypomagnesemia, and hypocalciuria. In the kidney tissues of
      SPAK(-/-) mice, the expression of total and phosphorylated (p-)NCC was markedly
      decreased, but that of p-OSR1, total NKCC2, and p-NKCC2 was significantly
      increased. We observed a blunted response to thiazide but normal response to
      furosemide in SPAK(-/-) mice. In aortic tissues, total NKCC1 expression was
      increased but p-NKCC1 was decreased in SPAK-deficient mice. Both SPAK(+/-) and
      SPAK(-/-) mice had impaired responses to the selective alpha(1)-adrenergic
      agonist phenylephrine and the NKCC1 inhibitor bumetanide, suggesting that
      impaired aortic contractility may contribute to the hypotension of SPAK-null
      mice. In summary, SPAK-null mice have defects of NCC in the kidneys and NKCC1 in
      the blood vessels, leading to hypotension through renal salt wasting and
      vasodilation. SPAK may be a promising target for antihypertensive therapy.

PMID- 20813866
TI  - Hemofiltration and hemodiafiltration reduce intradialytic hypotension in ESRD.
AB  - Symptomatic intradialytic hypotension is a common complication of hemodialysis
      (HD). The application of convective therapies to the outpatient setting may
      improve outcomes, including intradialytic hypotension. In this multicenter, open
      label, randomized controlled study, we randomly assigned 146 long-term dialysis
      patients to HD (n = 70), online predilution hemofiltration (HF; n = 36), or
      online predilution hemodiafiltration (HDF; n = 40). The primary end point was the
      frequency of intradialytic symptomatic hypotension (ISH). Compared with the run
      in period, the frequency of sessions with ISH during the evaluation period
      increased for HD (7.1 to 7.9%) and decreased for both HF (9.8 to 8.0%) and HDF
      (10.6 to 5.2%) (P < 0.001). Mean predialysis systolic BP increased by 4.2 mmHg
      among those who were assigned to HDF compared with decreases of 0.6 and 1.8 mmHg
      among those who were assigned to HD and HF, respectively (P = 0.038).
      Multivariate logistic regression demonstrated significant risk reductions in ISH
      for both HF (odds ratio 0.69; 95% confidence interval 0.51 to 0.92) and HDF (odds
      ratio 0.46, 95% confidence interval 0.33 to 0.63). There was a trend toward
      higher dropout for those who were assigned to HF (P = 0.107). In conclusion,
      compared with conventional HD, convective therapies (HDF and HF) reduce ISH in
      long-term dialysis patients.

PMID- 20813867
TI  - Regulation of WNK1 expression by miR-192 and aldosterone.
AB  - WNK1 and WNK4 encode two members of the WNK serine-threonine kinase subfamily.
      Greater WNK1 expression associates with higher BP. A combination of promoters,
      enhancers, repressors, and insulators regulate WNK1 expression, but whether
      microRNAs also modulate WNK1 expression is unknown. Here, computational analysis
      revealed the presence of a target sequence for miR-192 and miR-215 at the same
      site in the 3' untranslated region of the ubiquitous L- and the kidney-specific
      KS-WNK1. We functionally validated this target sequence by transient transfection
      and reporter assays. Although we observed expression of both miRs along the
      distal nephron, only miR-192 regulated endogenous WNK1 ex vivo. Furthermore, a
      potassium load, sodium depletion, and aldosterone infusion each significantly
      reduced miR-192 expression in the kidney. Taken together, these results suggest a
      miR-driven mechanism of gene regulation by aldosterone and a role for miR-192 in
      the regulation of sodium and potassium balance in the kidney.

PMID- 20813868
TI  - Where is the epidemic in kidney disease?

PMID- 20813869
TI  - Purinergic inhibition of ENaC produces aldosterone escape.
AB  - The mechanisms underlying "aldosterone escape," which refers to the excretion of
      sodium (Na(+)) during high Na(+) intake despite inappropriately increased levels
      of mineralocorticoids, are incompletely understood. Because local purinergic tone
      in the aldosterone-sensitive distal nephron downregulates epithelial Na(+)
      channel (ENaC) activity, we tested whether this mechanism mediates aldosterone
      escape. Here, urinary ATP concentration increased with dietary Na(+) intake in
      mice. Physiologic concentrations of ATP decreased ENaC activity in a dosage
      dependent manner. P2Y(2)(-/-) mice, which lack the purinergic receptor, had
      significantly less increased Na(+) excretion than wild-type mice in response to
      high-Na(+) intake. Exogenous deoxycorticosterone acetate and deletion of the
      P2Y(2) receptor each modestly increased the resistance of ENaC to changes in
      Na(+) intake; together, they markedly increased resistance. Under the latter
      condition, ENaC could not respond to changes in Na(+) intake. In contrast, as a
      result of aldosterone escape, wild-type mice had increased Na(+) excretion in
      response to high-Na(+) intake regardless of the presence of high
      deoxycorticosterone acetate. These data suggest that control of ENaC by
      purinergic signaling is necessary for aldosterone escape.

PMID- 20813871
TI  - QWERTY, @, &, #.

PMID- 20813870
TI  - Fibrosis with inflammation at one year predicts transplant functional decline.
AB  - Lack of knowledge regarding specific causes for late loss of kidney transplants
      hampers improvements in long-term allograft survival. Kidney transplants with
      both interstitial fibrosis and subclinical inflammation but not fibrosis alone
      after 1 year have reduced survival. This study tested whether fibrosis with
      inflammation at 1 year associates with decline of renal function in a low-risk
      cohort and characterized the nature of the inflammation. We studied 151 living
      donor, tacrolimus/mycophenolate-treated recipients without overt risk factors for
      reduced graft survival. Transplants with normal histology (n = 86) or fibrosis
      alone (n = 45) on 1-year protocol biopsy had stable renal function between 1 and
      5 years, whereas those with both fibrosis and inflammation (n = 20) exhibited a
      decline in GFR and reduced graft survival. Immunohistochemistry confirmed
      increased interstitial T cells and macrophages/dendritic cells in the group with
      both fibrosis and inflammation, and there was increased expression of transcripts
      related to innate and cognate immunity. Pathway- and pathologic process-specific
      analyses of microarray profiles revealed that potentially damaging immunologic
      activities were enriched among the overexpressed transcripts (e.g., Toll-like
      receptor signaling, antigen presentation/dendritic cell maturation, IFN-gamma
      inducible response, cytotoxic T lymphocyte-associated and acute rejection
      associated genes). Therefore, the combination of fibrosis and inflammation in 1
      year protocol biopsies associates with reduced graft function and survival as
      well as a rejection-like gene expression signature, even among recipients with no
      clinical risk factors for poor outcomes. Early interventions aimed at altering
      rejection-like inflammation may improve long-term survival of kidney allografts.

PMID- 20813872
TI  - Magnetization transfer MR imaging demonstrates degeneration of the subcortical
      and cortical gray matter in Huntington disease.
AB  - BACKGROUND AND PURPOSE: GM is typically affected in HD since the presymptomatic
      stage. Our aim was to investigate with MT MR imaging the microstructural changes
      of the residual brain subcortical and cortical GM in carriers of the HD gene and
      to preliminarily assess their correlation with the clinical features. MATERIALS
      AND METHODS: Fifteen HD gene carriers with a range of clinical severity and 15
      age- and sex-matched healthy controls underwent MT MR imaging on a 1.5T scanner.
      The MT ratio was measured automatically in several subcortical and cortical GM
      regions (striatal nuclei; thalami; and the neocortex of the frontal, temporal,
      parietal, and occipital lobes) by using FLS tools. RESULTS: The MT ratio was
      significantly (P < .05 with Bonferroni correction for multiple comparison)
      decreased in all subcortical structures except the putamen and decreased
      diffusely in the cerebral cortex of HD carriers compared with controls. Close
      correlation was observed between the subcortical and cortical regional MT ratios
      and several clinical variables, including disease duration, motor disability, and
      scores in timed neuropsychological tests. CONCLUSIONS: MT imaging demonstrates
      degeneration of the subcortical and cortical GM in HD carriers and might serve,
      along with volumetric assessment, as a surrogate marker in future clinical trials
      of HD.

PMID- 20813873
TI  - Endovascular parent artery occlusion for the treatment of wide-neck A1 segment
      aneurysms: a single-center experience.
AB  - The goal of this study was to evaluate the feasibility and efficacy of A1
      occlusion at the level of wide necked A1 aneurysms, where there are bilateral
      patent A1 segments and a patent AcomA. Between 2000 and 2010, 9 patients with
      wide necked A1 aneurysms were treated by coiling of the aneurysm along with
      parent vessel occlusion. All aneurysms had a wide neck (>= 4 mm). None were
      treated in the acute phase of a subarachnoid hemorrhage. Three small infarcts
      were noted on routine post-treatment head CT, 1 of which was symptomatic
      (transient hemiparesthesia). On control angiogram at 6 months or more, 3 A1
      recanalizations were found, 2 of which had a stable small neck recurrence. None
      of the aneurysms ruptured on follow-up. In this series, parent artery occlusion
      was effective in treating wide-necked aneurysms arising from the A1 segment in
      patients with adequate collateral supply.

PMID- 20813874
TI  - Long-term outcome in the repair of spinal cord perimedullary arteriovenous
      fistulas.
AB  - BACKGROUND AND PURPOSE: The natural history of PMAVFs, also known as type IV
      spinal cord AVFs, is incompletely understood. Both open surgical and endovascular
      approaches have been described as treatment modalities for this disease. The goal
      of this study was to evaluate the long-term outcome of patients with PMAVFs
      treated at a single tertiary care institution. MATERIALS AND METHODS: We
      conducted a retrospective study of 32 patients with PMAVFs, evaluated between
      1983 and 2009. Data were gathered by reviewing outpatient clinic notes, operative
      and radiologic reports, and spinal angiograms. The PMAVFs were categorized into 1
      of 3 types based on the angiographic imaging criteria. Pretreatment and
      posttreatment ambulation and micturition symptoms were quantified by using the
      ALS. RESULTS: Thirty patients underwent corrective procedures, 4 by embolization
      alone, 11 by surgery alone, and 15 with a combination of the 2. Twenty-eight
      patients underwent follow-up spinal angiography, with residual shunt noted in 6
      patients. The mean follow-up period was 54 months (range, 1-228 months). Analysis
      of the ALS scores revealed that treatment of PMAVFs, independent of technique,
      resulted in significant improvement in ambulation but inconsistent changes in
      micturition. In addition, residual fistula at the time of the follow-up angiogram
      was associated with worsened neurologic status or lack of improvement. Outcome
      analysis based on fistula type showed dramatic improvement in ALS ambulation
      scores (62%) for type 3 fistulas, compared with types 1 and 2 (26% and 27%,
      respectively). CONCLUSIONS: Significant improvement in ambulation but in not
      micturition was observed following treatment. Residual fistula on follow-up
      angiography was associated with progressive worsening or lack of improvement in
      neurologic function. Patients with type 3 fistulas were shown to benefit most
      from treatment, with marked improvement in posttreatment ambulation scores. As
      endovascular and surgical techniques continue to evolve, further studies are
      warranted.

PMID- 20813875
TI  - Intracranial dural arteriovenous fistula with retrograde cortical venous
      drainage: use of susceptibility-weighted imaging in combination with dynamic
      susceptibility contrast imaging.
AB  - BACKGROUND AND PURPOSE: SWI is a new MR imaging method that maximizes sensitivity
      to magnetic susceptibility effects with phase information for visualizing small
      cerebral veins. The purpose of this study was to report the use of SWI in
      combination with DSC in examining related RCVD in patients with intracranial
      DAVFs. MATERIALS AND METHODS: Ten patients with angiographically confirmed DAVFs
      with RCVD underwent conventional MR imaging, SWI, and DSC. The ability of SWI to
      depict dilated cerebral veins was evaluated and then compared with DSC. The
      hemispheres of patients with DAVFs were grouped into affected (with RCVD) or
      nonaffected (without RCVD) categories by angiography. Four patients had
      bilaterally affected hemispheres. A total of 14 affected hemispheres in patients
      with DAVFs with RCVD were evaluated. RESULTS: SWI showed dilated cerebral veins
      on the surface of the brain in all (100%) of the 14 affected hemispheres in
      patients with DAVFs with RCVD and deep in the brain in 9 (64%). T2-weighted
      imaging showed prominent flow-voids on the surface of the brain in 10 (71%) of
      the 14 affected hemispheres in patients with DAVFs with RCVD and deep in the
      brain in 5 (36%). DSC showed increased cerebral blood volume in all of the 14
      affected hemispheres. The SWI findings regarding dilated veins on the surface of
      the brain corresponded well with the areas of increased cerebral blood volume.
      CONCLUSIONS: SWI in combination with DSC could be used to characterize the
      presence of RCVD in patients with DAVFs.

PMID- 20813876
TI  - Establishment of a UK-wide network to facilitate the acquisition of quality
      assured FDG-PET data for clinical trials in lymphoma.
AB  - BACKGROUND: Multicentre trials are required to determine how [fluorine-18]-2
      fluoro-2-deoxy-D-glucose-positron emission tomography imaging can guide cancer
      treatment. Consistency in quality control (QC), scan acquisition and reporting is
      mandatory for high-quality results, which are comparable across sites. METHODS: A
      national positron emission tomography (PET) clinical trials network (CTN) has
      been set up with a 'core laboratory' to coordinate QC and interpret scans. The
      CTN is involved in trials in Hodgkin's lymphoma [Randomised Phase III trial to
      determine the role of FDG-PET Imaging in Clinical Stages IA/IIA Hodgkin's Disease
      (RAPID) and Randomised Phase III trial to assess response adapted therapy using
      FDG-PET imaging in patients with newly diagnosed, advanced Hodgkin lymphoma
      (RATHL)] and diffuse large B-cell lymphoma [Blinded evaluation of prognostic
      value of FDG-PET after 2 cycles of chemotherapy in diffuse large B-cell Non
      Hodgkins Lymphoma, a sub-study of the R-CHOP-21 vs R-CHOP-14 trial (R-CHOP PET
      substudy)]. Approval to join requires scanner validation and agreement to follow
      a standard QC protocol. Scans are transferred to the core laboratory and reported
      centrally according to predetermined criteria. RESULTS: The qualification
      procedure was carried out on 15 scanners. All scanners were able to demonstrate
      the necessary quantitative accuracy, and following modification of image
      reconstruction where necessary, scanners demonstrated comparable recovery
      coefficients (RCs) indicating similar performance. The average RC (+/-1 standard
      deviation) was 0.56 +/- 0.095 for the 13-mm sphere. Reports from 444 of 473 (94%)
      patients in RAPID and 67 of 73 (92%) patients in RATHL were available for
      randomisation of therapy. CONCLUSIONS: The CTN has enabled consistent quality
      assured PET results to be obtained from multiple centres in time for clinical
      decision making. The results of trials will be significantly strengthened by this
      system.

PMID- 20813877
TI  - Leukotrienes modulate secretion of progesterone and prostaglandins during the
      estrous cycle and early pregnancy in cattle: an in vivo study.
AB  - Recently, we showed that leukotrienes (LTs) regulate ovarian cell function in
      vitro. The aim of this study was to examine the role of LTs in corpus luteum (CL)
      function during both the estrous cycle and early pregnancy in vivo. mRNA
      expression of LT receptors (BLT for LTB(4) and CYSLT for LTC(4)), and 5
      lipoxygenase (5-LO) in CL tissue and their localization in the ovary were studied
      during the estrous cycle and early pregnancy. Moreover, concentrations of LTs
      (LTB(4) and C(4)) in the CL tissue and blood were measured. 5-LO and BLT mRNA
      expression increased on days 16-18 of the cycle, whereas CYSLT mRNA expression
      increased on days 16-18 of the pregnancy. The level of LTB(4) was evaluated
      during pregnancy compared with the level of LTC(4), which increased during CL
      regression. LT antagonists influenced the duration of the estrous cycle: the
      LTC(4) antagonist (azelastine) prolonged the luteal phase, whereas the LTB(4)
      antagonist (dapsone) caused earlier luteolysis in vivo. Dapsone decreased
      progesterone (P(4)) secretion and azelastine increased P(4) secretion during the
      estrous cycle. In summary, LT action in the bovine reproductive tract is
      dependent on LT type: LTB(4) is luteotropic during the estrous cycle and supports
      early pregnancy, whereas LTC(4) is luteolytic, regarded as undesirable in early
      pregnancy. LTs are produced/secreted in the CL tissue, influence prostaglandin
      function, and serve as important factors during the estrous cycle and early
      pregnancy in cattle.

PMID- 20813878
TI  - Global modeling of transcriptional responses in interaction networks.
AB  - MOTIVATION: Cell-biological processes are regulated through a complex network of
      interactions between genes and their products. The processes, their activating
      conditions and the associated transcriptional responses are often unknown.
      Organism-wide modeling of network activation can reveal unique and shared
      mechanisms between tissues, and potentially as yet unknown processes. The same
      method can also be applied to cell-biological conditions in one or more tissues.
      RESULTS: We introduce a novel approach for organism-wide discovery and analysis
      of transcriptional responses in interaction networks. The method searches for
      local, connected regions in a network that exhibit coordinated transcriptional
      response in a subset of tissues. Known interactions between genes are used to
      limit the search space and to guide the analysis. Validation on a human pathway
      network reveals physiologically coherent responses, functional relatedness
      between tissues and coordinated, context-specific regulation of the genes.
      AVAILABILITY: Implementation is freely available in R and Matlab at
      http://www.cis.hut.fi/projects/mi/software/NetResponse

PMID- 20813879
TI  - A targeted UAS-RNAi screen in Drosophila larvae identifies wound closure genes
      regulating distinct cellular processes.
AB  - Robust mechanisms for tissue repair are critical for survival of multicellular
      organisms. Efficient cutaneous wound repair requires the migration of cells at
      the wound edge and farther back within the epidermal sheet, but the genes that
      control and coordinate these migrations remain obscure. This is in part because a
      systematic screening approach for in vivo identification and classification of
      postembryonic wound closure genes has yet to be developed. Here, we performed a
      proof-of-principle reporter-based in vivo RNAi screen in the Drosophila
      melanogaster larval epidermis to identify genes required for normal wound
      closure. Among the candidate genes tested were kinases and transcriptional
      mediators of the Jun N-terminal kinase (JNK) signaling pathway shown to be
      required for epithelial sheet migration during development. Also targeted were
      genes involved in actin cytoskeletal remodeling. Importantly, RNAi knockdown of
      both canonical and noncanonical members of the JNK pathway caused open wounds, as
      did several genes involved in actin cytoskeletal remodeling. Our analysis of JNK
      pathway components reveals redundancy among the upstream activating kinases and
      distinct roles for the downstream transcription factors DJun and DFos.
      Quantitative and qualitative morphological classification of the open wound
      phenotypes and evaluation of JNK activation suggest that multiple cellular
      processes are required in the migrating epidermal cells, including functions
      specific to cells at the wound edge and others specific to cells farther back
      within the epidermal sheet. Together, our results identify a new set of conserved
      wound closure genes, determine putative functional roles for these genes within
      the migrating epidermal sheet, and provide a template for a broader in vivo RNAi
      screen to discover the full complement of genes required for wound closure during
      larval epidermal wound healing.

PMID- 20813880
TI  - Conditions under which genome-wide association studies will be positively
      misleading.
AB  - Genome-wide association mapping is a popular method for using natural variation
      within a species to generate a genotype-phenotype map. Statistical association
      between an allele at a locus and the trait in question is used as evidence that
      variation at the locus is responsible for variation of the trait. Indirect
      association, however, can give rise to statistically significant results at loci
      unrelated to the trait. We use a haploid, three-locus, binary genetic model to
      describe the conditions under which these indirect associations become stronger
      than any of the causative associations in the organism--even to the point of
      representing the only associations present in the data. These indirect
      associations are the result of disequilibrium between multiple factors affecting
      a single trait. Epistasis and population structure can exacerbate the problem but
      are not required to create it. From a statistical point of view, indirect
      associations are true associations rather than the result of stochastic noise:
      they will not be ameliorated by increasing sampling size or marker density and
      can be reproduced in independent studies.

PMID- 20813881
TI  - When Cre-mediated recombination in mice does not result in protein loss.
AB  - Cre/loxP recombination enables cellular specificity and, in the case of inducible
      systems, temporal control of genomic deletions. Here we used a SM22alpha
      tamoxifen-inducible Cre line to inactivate beta1 integrin in adult smooth muscle.
      Interestingly, analysis of two distinct beta1 loxP transgenic mice revealed
      vastly different outcomes after beta1 integrin deletion. Lethality occurred 4
      weeks postinduction in one Cre/loxP line, while no apparent phenotype was seen in
      the other line. Genetic analysis revealed appropriate DNA excision in both cases;
      however, differences were found in the degree of protein loss with absolutely no
      change in protein levels in the model that lacked a phenotype. Seeking to
      understand protein persistence despite appropriate recombination, we first
      validated the flox allele using a constitutive Cre line and demonstrated its
      ability to mediate effective protein inactivation. We then examined the
      possibility of heterozygous cell selection, protein turnover, and deletion
      efficiency with no success for explaining the phenotype. Finally, we documented
      the presence of the Cre-recombination episomal product, which persisted in tissue
      samples with no protein loss. The product was only noted in cells with low
      proliferative capacity. These findings highlight the potential for protein
      expression from the products of Cre-recombinase excised genes, particularly when
      deletion occurs in low turnover populations.

PMID- 20813882
TI  - Prediction of genetic values of quantitative traits in plant breeding using
      pedigree and molecular markers.
AB  - The availability of dense molecular markers has made possible the use of genomic
      selection (GS) for plant breeding. However, the evaluation of models for GS in
      real plant populations is very limited. This article evaluates the performance of
      parametric and semiparametric models for GS using wheat (Triticum aestivum L.)
      and maize (Zea mays) data in which different traits were measured in several
      environmental conditions. The findings, based on extensive cross-validations,
      indicate that models including marker information had higher predictive ability
      than pedigree-based models. In the wheat data set, and relative to a pedigree
      model, gains in predictive ability due to inclusion of markers ranged from 7.7 to
      35.7%. Correlation between observed and predictive values in the maize data set
      achieved values up to 0.79. Estimates of marker effects were different across
      environmental conditions, indicating that genotype * environment interaction is
      an important component of genetic variability. These results indicate that GS in
      plant breeding can be an effective strategy for selecting among lines whose
      phenotypes have yet to be observed.

PMID- 20813883
TI  - Lambda red recombineering in Escherichia coli occurs through a fully single
      stranded intermediate.
AB  - The phage lambda-derived Red recombination system is a powerful tool for making
      targeted genetic changes in Escherichia coli, providing a simple and versatile
      method for generating insertion, deletion, and point mutations on chromosomal,
      plasmid, or BAC targets. However, despite the common use of this system, the
      detailed mechanism by which lambda Red mediates double-stranded DNA recombination
      remains uncertain. Current mechanisms posit a recombination intermediate in which
      both 5' ends of double-stranded DNA are recessed by lambda exonuclease, leaving
      behind 3' overhangs. Here, we propose an alternative in which lambda exonuclease
      entirely degrades one strand, while leaving the other strand intact as single
      stranded DNA. This single-stranded intermediate then recombines via beta
      recombinase-catalyzed annealing at the replication fork. We support this by
      showing that single-stranded gene insertion cassettes are recombinogenic and that
      these cassettes preferentially target the lagging strand during DNA replication.
      Furthermore, a double-stranded DNA cassette containing multiple internal
      mismatches shows strand-specific mutations cosegregating roughly 80% of the time.
      These observations are more consistent with our model than with previously
      proposed models. Finally, by using phosphorothioate linkages to protect the
      lagging-targeting strand of a double-stranded DNA cassette, we illustrate how our
      new mechanistic knowledge can be used to enhance lambda Red recombination
      frequency. The mechanistic insights revealed by this work may facilitate further
      improvements to the versatility of lambda Red recombination.

PMID- 20813884
TI  - Sex differences in mortality and clinical expressions of patients with chronic
      obstructive pulmonary disease. The TORCH experience.
AB  - RATIONALE: There is limited knowledge regarding sex differences and outcomes in
      patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES: Determine
      sex differences in survival, causes of death, and patient-centered outcomes in
      the 3-year Toward a Revolution in COPD Health (TORCH) study. METHODS: A total of
      1,481 women and 4,631 men with COPD were enrolled in TORCH, a trial comparing
      salmeterol, 50 MUg, plus fluticasone propionate, 500 MUg, twice a day and each
      component individually. Causes of death were determined by an endpoint committee.
      Sex differences in survival were explored using a Cox proportional hazards model
      adjusted for other baseline factors. Exacerbation rate was compared using a
      negative binomial model. Dyspnea was evaluated using the Medical Research Council
      scale and health status using the St. George's Respiratory Questionnaire.
      MEASUREMENTS AND MAIN RESULTS: At baseline, women were younger (63 vs. 66 yr),
      had higher FEV(1) (47% vs. 44% predicted), and worse St. George's Respiratory
      Questionnaire (51.3 vs. 48.7) and Medical Research Council score. During the
      study, 707 (15.3%) men and 168 (11.3%) women died. After adjusting for
      differences in baseline factors, the risk of dying was 16% higher in men than in
      women; however, this was not statistically significant (hazard ratio 1.16 [95%
      CI, 0.98-1.39]). Causes of death were similar in women and men. Exacerbation rate
      was 25% higher in women than in men. CONCLUSIONS: Women enrolled in TORCH had a
      lower mortality rate than men but similar causes of death. The risk of dying was
      similar in women and men after adjusting for important baseline variables. Women
      reported more exacerbations, and worse dyspnea and health status scores than men.
      Clinical trial registered with www.clinicaltrials.gov (NCT00268216).

PMID- 20813885
TI  - Persisting remodeling and less airway wall eosinophil activation in complete
      remission of asthma.
AB  - RATIONALE: Individuals with asthma may outgrow symptoms despite not using
      treatment, whereas others reach complete remission (CoR) with absence of airway
      obstruction and bronchial hyperresponsiveness. It is uncertain whether this
      associates with remission of all inflammatory and remodeling asthma features.
      OBJECTIVES: To compare the pathologic phenotype of individuals with asthma with
      CoR and clinical remission (ClinR) and those with active asthma, with and without
      the use of inhaled corticosteroids (ICS). METHODS: We investigated 165
      individuals known with active asthma, on reexamination having CoR (n = 18), ClinR
      (n = 44), and current asthma (CuA, n = 103, 64 with and 39 without ICS).
      MEASUREMENTS MAIN RESULTS: Inflammatory cells were measured in blood, induced
      sputum, and bronchial biopsies; histamine and ECP in sputum; and eosinophilic
      peroxidase (EPX) immunopositivity and remodeling (epithelial changes, E-cadherin
      expression, basement membrane [BM] thickening, collagen deposition) in bronchial
      biopsies. Median (range) blood eosinophils from CoR were significantly lower than
      those from CuA (0.10 [0.04-0.24] vs. 0.18 [0.02-1.16] * 109/L). Bronchial EPX
      immunopositivity was lower in CoR than in both ClinR and CuA (67 [0.5-462] vs. 95
      [8-5329] and 172 [6-5313] pixels). Other inflammatory findings were comparable.
      BM thickness was lowest in CuA, caused by lower BM thickness in those using ICS
      (CoR, 6.3 [4.7-8.4]; ClinR, 6.5 [3.8-11.7]; CuA, 5.7 [2.8-12.6]; and ICS using
      CuA, 5.3 [2.8-8.2] MUm). CONCLUSIONS: CoR is still accompanied by airway
      abnormalities because BM thickness is similar in individuals with asthma with
      CoR, ClinR, and CuA without ICS. Airway eosinophilic activation best
      differentiates these three groups, signifying their importance in the clinical
      expression and severity of bronchial hyperresponsiveness in asthma.

PMID- 20813886
TI  - Standardizing measurement of chronic obstructive pulmonary disease exacerbations.
      Reliability and validity of a patient-reported diary.
AB  - RATIONALE: Although exacerbations are an important problem in chronic obstructive
      pulmonary disease (COPD) and a target of intervention, there is no valid,
      standardized tool for assessing their frequency, severity, and duration.
      OBJECTIVES: This study tested the properties of the Exacerbations of Chronic
      Pulmonary Disease Tool (EXACT), a new patient-reported outcome diary. METHODS: A
      prospective, two-group, observational study was conducted in patients with COPD.
      The acute group (n = 222) was enrolled during a clinic visit for exacerbation
      with follow-up visits on Days 10, 29, and 60. The stable group (n = 188),
      recruited by telephone or during routine visits, was exacerbation free for at
      least 60 days. MEASUREMENTS AND MAIN RESULTS: Acute patients completed the diary
      on Days 1-29 and 60-67; stable patients for 7 days. All patients provided stable
      state spirometry and completed the St. George Respiratory Questionnaire-COPD
      (SGRQ-C). Acute patient assessments included clinician and patient global ratings
      of exacerbation severity and recovery. Mean age of the sample (n = 410) was 65
      (+/- 10) years; 48% were male; stable FEV1 was 51% predicted (+/- 20). Internal
      consistency (Pearson separation index) for the EXACT was 0.92, 1-week
      reproducibility (stable patients; intraclass correlation) was 0.77. EXACT scores
      correlated with SGRQ-C (r = 0.64; P < 0.0001) and differentiated acute and stable
      patients (P < 0.0001). In acute patients, scores improved over time (P < 0.0001)
      and differentiated between degrees of clinician-rated exacerbation severity (P <
      0.05). EXACT change scores differentiated responders and nonresponders on Day 10,
      as judged by clinicians or patients (P < 0.0001). CONCLUSIONS: Results suggest
      the EXACT is reliable, valid, and sensitive to change with exacerbation recovery.

PMID- 20813887
TI  - Rapidly progressive diaphragmatic weakness and injury during mechanical
      ventilation in humans.
AB  - RATIONALE: Diaphragmatic function is a major determinant of the ability to
      successfully wean patients from mechanical ventilation (MV). Paradoxically, MV
      itself results in a rapid loss of diaphragmatic strength in animals. However,
      very little is known about the time course or mechanistic basis for such a
      phenomenon in humans. OBJECTIVES: To determine in a prospective fashion the time
      course for development of diaphragmatic weakness during MV; and the relationship
      between MV duration and diaphragmatic injury or atrophy, and the status of
      candidate cellular pathways implicated in these phenomena. METHODS: Airway
      occlusion pressure (TwPtr) generated by the diaphragm during phrenic nerve
      stimulation was measured in short-term (0.5 h; n = 6) and long-term (>5 d; n = 6)
      MV groups. Diaphragmatic biopsies obtained during thoracic surgery (MV for 2-3 h;
      n = 10) and from brain-dead organ donors (MV for 24-249 h; n = 15) were analyzed
      for ultrastructural injury, atrophy, and expression of proteolysis-related
      proteins (ubiquitin, nuclear factor-kappaB, and calpains). MEASUREMENTS AND MAIN
      RESULTS: TwPtr decreased progressively during MV, with a mean reduction of 32 +/-
      6% after 6 days. Longer periods of MV were associated with significantly greater
      ultrastructural fiber injury (26.2 +/- 4.8 vs. 4.7 +/- 0.6% area), decreased
      cross-sectional area of muscle fibers (1,904 +/- 220 vs. 3,100 +/- 329 MUm2), an
      increase of ubiquitinated proteins (+19%), higher expression of p65 nuclear
      factor-kappaB (+77%), and greater levels of the calcium-activated proteases
      calpain-1, -2, and -3 (+104%, +432%, and +266%, respectively) in the diaphragm.
      CONCLUSIONS: Diaphragmatic weakness, injury, and atrophy occur rapidly in
      critically ill patients during MV, and are significantly correlated with the
      duration of ventilator support.

PMID- 20813888
TI  - Physical activity and right ventricular structure and function. The MESA-Right
      Ventricle Study.
AB  - RATIONALE: Intense exercise in elite athletes is associated with increased left
      ventricular (LV) and right ventricular (RV) mass and volumes. However, the effect
      of physical activity on the RV in an older community-based population is unknown.
      OBJECTIVES: We studied the association between levels of physical activity in
      adults and RV mass and volumes. METHODS: The Multi-Ethnic Study of
      Atherosclerosis (MESA) performed cardiac magnetic resonance imaging on community
      based participants without clinical cardiovascular disease. RV volumes were
      determined from manually contoured endocardial margins. RV mass was determined
      from the difference between epicardial and endocardial volumes multiplied by the
      specific gravity of myocardium. Metabolic equivalent-minutes/day were calculated
      from the self-reported frequency, duration, and intensity of physical activity.
      MEASUREMENTS AND MAIN RESULTS: The study sample (n = 1,867) was aged 61.8 +/- 10
      years, 48% male, 44% white, 27% African American, 20% Hispanic, and 9% Chinese.
      Higher levels of moderate and vigorous physical activity were linearly associated
      with higher RV mass (P = 0.02) after adjusting for demographics, anthropometrics,
      smoking, cholesterol, diabetes mellitus, hypertension, and LV mass. Higher levels
      of intentional exercise (physical activity done for the sole purpose of
      conditioning or fitness) were nonlinearly associated with RV mass independent of
      LV mass (P = 0.03). There were similar associations between higher levels of
      physical activity and larger RV volumes. CONCLUSIONS: Higher levels of physical
      activity in adults were associated with greater RV mass independent of the
      associations with LV mass; similar results were found for RV volumes. Exercise
      associated RV remodeling may have important clinical implications.

PMID- 20813889
TI  - Genetic variation in the FAS gene and associations with acute lung injury.
AB  - RATIONALE: Fas (CD95) modulates apoptosis and inflammation and is believed to
      play an important role in lung injury. OBJECTIVES: To determine if common genetic
      variation in FAS is associated with acute lung injury (ALI) susceptibility, risk
      of death, and FAS gene expression. METHODS: We genotyped 14 single nucleotide
      polymorphisms (tagSNPS) in FAS in samples from healthy white volunteers (control
      subjects, n = 294) and patients with ALI (cases, n = 324) from the ARDSnet Fluid
      and Catheter Treatment Trial (FACTT). FAS genotypes associated with ALI in the
      discovery study were confirmed in a nested case-control validation study of
      critically ill patients at risk for ALI (n = 657). We also tested for
      associations between selected tagSNPS and FAS mRNA levels in whole blood from
      healthy control subjects exposed to media alone or LPS ex vivo. MEASUREMENTS AND
      MAIN RESULTS: We identified associations between four tagSNPs in FAS (FAS(
      11341A>T) [rs17447140], FAS(9325G>A) [rs2147420], FAS(21541C>T) [rs2234978], and
      FAS(24484A>T) [rs1051070]) and ALI case status. Haplotype-based analyses
      suggested that three of the tagSNPs (FAS(9325G>A), FAS(21541C>T), and
      FAS(24484A>T)) function as a unit. The association with this haplotype and ALI
      was validated in a nested case-control study of at-risk subjects (P = 0.05). This
      haplotype was also associated with increased FAS mRNA levels in response to LPS
      stimulation. There was no association between FAS polymorphisms and risk of death
      among ALI cases. CONCLUSIONS: Common genetic variants in FAS are associated with
      ALI susceptibility. This is the first genetic evidence supporting a role for FAS
      in ALI.

PMID- 20813890
TI  - Mast cell phenotype, location, and activation in severe asthma. Data from the
      Severe Asthma Research Program.
AB  - RATIONALE: Severe asthma (SA) remains poorly understood. Mast cells (MC) are
      implicated in asthma pathogenesis, but it remains unknown how their phenotype,
      location, and activation relate to asthma severity. OBJECTIVES: To compare MC
      related markers measured in bronchoscopically obtained samples with clinically
      relevant parameters between normal subjects and subjects with asthma to clarify
      their pathobiologic importance. METHODS: Endobronchial biopsies, epithelial
      brushings, and bronchoalveolar lavage were obtained from subjects with asthma and
      normal subjects from the Severe Asthma Research Program (N = 199). Tryptase,
      chymase, and carboxypeptidase A (CPA)3 were used to identify total MC (MC(Tot))
      and the MC(TC) subset (MCs positive for both tryptase and chymase) using
      immunostaining and quantitative real-time polymerase chain reaction. Lavage was
      analyzed for tryptase and prostaglandin D2 (PGD2) by ELISA. MEASUREMENTS AND MAIN
      RESULTS: Submucosal MC(Tot) (tryptase-positive by immunostaining) numbers were
      highest in "mild asthma/no inhaled corticosteroid (ICS) therapy" subjects and
      decreased with greater asthma severity (P = 0.002). In contrast, MC(TC) (chymase
      positive by immunostaining) were the predominant (MC(TC)/MC(Tot) > 50%) MC
      phenotype in SA (overall P = 0.005). Epithelial MC(Tot) were also highest in mild
      asthma/no ICS, but were not lower in SA. Instead, they persisted and were
      predominantly MC(TC). Epithelial CPA3 and tryptase mRNA supported the
      immunostaining data (overall P = 0.008 and P = 0.02, respectively). Lavage PGD2
      was higher in SA than in other steroid-treated groups (overall P = 0.02), whereas
      tryptase did not differentiate the groups. In statistical models, PGD2 and
      MC(TC)/MC(Tot) predicted SA. CONCLUSIONS: Severe asthma is associated with a
      predominance of MC(TC) in the airway submucosa and epithelium. Activation of
      those MC(TC) may contribute to the increases in PGD2 levels. The data suggest an
      altered and active MC population contributes to SA pathology.

PMID- 20813892
TI  - Diabetic retinopathy screening using tele-ophthalmology in a primary care
      setting.
AB  - We evaluated tele-ophthalmology for diabetic retinopathy screening in a primary
      care setting. Four general practitioners (GPs) were taught to assess non
      mydriatic retinography images of patients with diabetes. After training, a total
      of 1223 patients were screened using this method: 926 (76%) did not have diabetic
      retinopathy and 297 (24%) were referred for an ophthalmologic assessment. Of the
      297 patients, 186 (15%) did not have diabetic retinopathy and were considered to
      be false positives, 85 (7%) had diabetic retinopathy and in 26 cases (2%) the
      retinography images were unreadable. The specificity of GPs for detecting
      diabetic retinopathy by non-mydriatic retinography was 83%. Ophthalmologists also
      assessed 120 patients who had been diagnosed as normal to detect false negatives.
      Ten patients (8.3%) had mild non-proliferative diabetic retinopathy with small
      isolated retinal hemorrhages. Only one patient (0.8%) had treatable diabetic
      retinopathy with hard exudates and microaneurysms. The sensitivity of GPs for
      detecting diabetic retinopathy was 90.9%; the sensitivity for detecting treatable
      lesions was 99.2%. We concluded that adequately trained GPs can screen for
      treatable lesions of diabetic retinopathy with a very high level of reliability
      using non-mydriatic retinography.

PMID- 20813893
TI  - Telehealth in palliative care in the UK: a review of the evidence.
AB  - We reviewed telehealth applications which were being used in palliative care
      settings in the UK. Electronic database searches (Medline, CINAHL, PsychInfo and
      Embase), searches of the grey literature and cited author searches were
      conducted. In total, 111 papers were identified and 21 documents were included in
      the review. Telehealth was being used by a range of health professionals in
      oncology care settings that included specialist palliative care, hospices,
      primary care settings, nursing homes and hospitals as well as patients and
      carers. The most common applications were: out-of-hours telephone support, advice
      services for palliative care patients, carers and health professionals,
      videoconferencing for interactive case discussions, consultations and
      assessments, and training and education of palliative care and other health-care
      staff. The review suggests that current technology is usable and acceptable to
      patients and health professionals in palliative care settings. However, there are
      several challenges in integrating telehealth into routine practice.

PMID- 20813891
TI  - Decreased neprilysin and pulmonary vascular remodeling in chronic obstructive
      pulmonary disease.
AB  - RATIONALE: Studies with genetically engineered mice showed that decreased
      expression of the transmembrane peptidase neprilysin (NEP) increases
      susceptibility to hypoxic pulmonary vascular remodeling and hypertension; in
      hypoxic wild-type mice, expression is decreased early in distal pulmonary
      arteries, where prominent vascular remodeling occurs. Therefore, in humans with
      smoke- and hypoxia-induced vascular remodeling, as in chronic obstructive
      pulmonary disease (COPD), pulmonary activity/expression of NEP may likewise be
      decreased. OBJECTIVES: To test whether NEP activity and expression are reduced in
      COPD lungs and pulmonary arterial smooth muscle cells (SMCs) exposed to cigarette
      smoke extract or hypoxia and begin to investigate mechanisms involved. METHODS:
      Control and advanced COPD lung lysates (n = 13-14) were analyzed for NEP activity
      and protein and mRNA expression. As a control, dipeptidyl peptidase IV activity
      was analyzed. Lung sections were assessed for vascular remodeling and oxidant
      damage. Human pulmonary arterial SMCs were exposed to cigarette smoke extract,
      hypoxia, or H2O2, and incubated with antioxidants or lysosomal/proteasomal
      inhibitors. MEASUREMENTS AND MAIN RESULTS: COPD lungs demonstrated areas of
      vascular rarification, distal muscularization, and variable intimal and prominent
      medial/adventitial thickening. NEP activity was reduced by 76%; NEP protein
      expression was decreased in alveolar walls and distal vessels; mRNA expression
      was also decreased. In SMCs exposed to cigarette smoke extract, hypoxia, and
      H2O2, NEP activity and expression were also reduced. Reactive oxygen species
      inactivated NEP activity; NEP protein degradation appeared to be substantially
      induced. CONCLUSIONS: Mechanisms responsible for reduced NEP activity and protein
      expression include oxidative reactions and protein degradation. Maintaining or
      increasing lung NEP may protect against pulmonary vascular remodeling in response
      to chronic smoke and hypoxia.

PMID- 20813894
TI  - The reach of a hepatitis B vaccination programme among men who have sex with men.
AB  - BACKGROUND: Homosexual contact is a major risk factor for acute hepatitis B
      infection. This study explores how many and which men who have sex with men (MSM)
      are reached by the ongoing hepatitis B vaccination programme in The Netherlands
      (started in 2002), and investigate reasons for non-participation and non
      compliance. METHODS: In this cross-sectional study, on the basis of ethnographic
      mapping and targeted sampling, 320 MSM were interviewed at different venues in
      three regions in The Netherlands. RESULTS: Of the sample, 74% reported to be
      aware of the opportunity to obtain free hepatitis B vaccination, and 50% reported
      to be vaccinated (received at least one injection). Compliance with the three
      dose vaccination schedule was 84%. The most important reason for non
      participation in the vaccination programme was a low perceived risk of getting
      infected with the virus. A personal approach by STD-prevention workers, the
      recruitment region and having sex with casual partners were positively associated
      with vaccination uptake. Being bisexual was negatively associated with, and
      visiting gay bars/discos was positively associated with, awareness of the
      opportunity to obtain free hepatitis B vaccination. CONCLUSION: This study shows
      a large proportion of MSM is aware that they could opt for free hepatitis B
      vaccination. Future vaccination programmes should focus on a personal approach,
      since the use of STD prevention workers was shown to be a successful tool for
      participation in the vaccination programme. The personal information should focus
      on perceived risk of infection, since this was a major reason for vaccine
      refusal.

PMID- 20813895
TI  - The validity of the mortality to incidence ratio as a proxy for site-specific
      cancer survival.
AB  - BACKGROUND: The complement of the cancer mortality to incidence ratio [1-(M/I)]
      has been suggested as a valid proxy for 5-year relative survival. Whether this
      suggestion holds true for all types of cancer has not yet been adequately
      evaluated. METHODS: We used publicly available databases of cancer incidence,
      cancer mortality and relative survival to correlate relative survival estimates
      and 1-(M/I) estimates from Denmark, Finland, Iceland, Norway, Sweden, the USA and
      the Netherlands. We visually examined for which tumour sites 5-year relative
      survival cannot simply be predicted by the 1-(M/I) and evaluated similarities
      between countries. RESULTS: Country-specific linear regression analyses show that
      there is no systematic bias in predicting 5-year relative survival by 1-(M/I) in
      five countries. There is a small but significant systematic underestimation of
      survival from prognostically poor tumour sites in two countries. Furthermore, the
      1-(M/I) overestimates survival from oral cavity and liver cancer with >10% in at
      least two of the seven countries. By contrast, the proxy underestimates survival
      from soft tissue, bone, breast, prostate and oesophageal cancer, multiple myeloma
      and leukaemia with >10% in at least two of the seven countries. CONCLUSION: The 1
      (M/I) is a good approximation of the 5-year relative survival for most but not
      all tumour sites.

PMID- 20813896
TI  - Antibody targeting KIT as pretransplantation conditioning in immunocompetent
      mice.
AB  - Inherited hematologic defects that lack an in vivo selective advantage following
      gene correction may benefit from effective yet minimally toxic cytoreduction of
      endogenous hematopoietic stem cells (HSCs) prior to transplantation of gene
      modified HSCs. We studied the efficacy of administering a novel sequential
      treatment of parenteral ACK2, an antibody that blocks KIT, followed by low-dose
      irradiation (LD-IR) for conditioning of wild-type and X-linked chronic
      granulomatous disease (X-CGD) mice. In wild-type mice, combining ACK2 and LD-IR
      profoundly decreased endogenous competitive long-term HSC repopulating activity,
      and permitted efficient and durable donor-derived HSC engraftment after congenic
      transplantation. ACK2 alone was ineffective. The combination of ACK2 and LD-IR
      was also effective conditioning in X-CGD mice for engraftment of X-CGD donor HSCs
      transduced ex vivo with a lentiviral vector. We conclude that combining ACK2 with
      LD-IR is a promising approach to effectively deplete endogenous HSCs and
      facilitate engraftment of transplanted donor HSCs.

PMID- 20813897
TI  - AIDS-related Burkitt lymphoma in the United States: what do age and CD4
      lymphocyte patterns tell us about etiology and/or biology?
AB  - Trimodal or bimodal age-specific incidence rates for Burkitt lymphoma (BL) were
      observed in the United States general population, but the role of
      immunosuppression could not be excluded. Incidence rates, rate ratios, and 95%
      confidence intervals for BL and other non-Hodgkin lymphoma (NHL), by age and CD4
      lymphocyte count categories, were estimated using Poisson regression models using
      data from the United States HIV/AIDS Cancer Match study (1980-2005). BL incidence
      was 22 cases per 100 000 person-years and 586 for non-BL NHL. Adjusted BL
      incidence rate ratio among males was 1.6* that among females and among non
      Hispanic blacks, 0.4* that among non-Hispanic whites, but unrelated to HIV
      transmission category. Non-BL NHL incidence increased from childhood to
      adulthood; in contrast, 2 age-specific incidence peaks during the pediatric and
      adult/geriatric years were observed for BL. Non-BL NHL incidence rose steadily
      with decreasing CD4 lymphocyte counts; in contrast, BL incidence was lowest among
      people with <= 50 CD4 lymphocytes/MUL versus those with >= 250 CD4
      lymphocytes/MUL (incidence rate ratio 0.3 [95% confidence interval = 0.2-0.6]).
      The bimodal peaks for BL, in contrast to non-BL NHL, suggest effects of
      noncumulative risk factors at different ages. Underascertainment or biological
      reasons may account for BL deficit at low CD4 lymphocyte counts.

PMID- 20813898
TI  - Nogo-B receptor is essential for angiogenesis in zebrafish via Akt pathway.
AB  - Our previous work has shown that axon guidance gene family Nogo-B and its
      receptor (NgBR) are essential for chemotaxis and morphogenesis of endothelial
      cells in vitro. To investigate NogoB-NgBR function in vivo, we cloned the
      zebrafish ortholog of both genes and studied loss of function in vivo using
      morpholino antisense technology. Zebrafish ortholog of Nogo-B is expressed in
      somite while expression of zebrafish NgBR is localized in intersomitic vessel
      (ISV) and axial dorsal aorta during embryonic development. NgBR or Nogo-B
      knockdown embryos show defects in ISV sprouting in the zebrafish trunk.
      Mechanistically, we found that NgBR knockdown not only abolished its ligand Nogo
      B-stimulated endothelial cell migration but also reduced the vascular endothelial
      growth factor (VEGF)-stimulated phosphorylation of Akt and vascular endothelial
      growth factor-induced chemotaxis and morphogenesis of human umbilical vein
      endothelial cells. Further, constitutively activated Akt (myristoylated [myr]Akt)
      or human NgBR can rescue the NgBR knockdown umbilical vein endothelial cell
      migration defects in vitro or NgBR morpholino-caused ISV defects in vivo. These
      data place Akt at the downstream of NgBR in both Nogo-B- and VEGF-coordinated
      sprouting of ISVs. In summary, this study identifies the in vivo functional role
      for Nogo-B and its receptor (NgBR) in angiogenesis in zebrafish.

PMID- 20813899
TI  - Role for vitamin D receptor in the neuronal control of the hematopoietic stem
      cell niche.
AB  - Hematopoietic stem/progenitor cells (HSPCs) are released from the bone marrow to
      the circulation by the cytokine, granulocyte colony-stimulating factor, via
      sympathetic nervous system (SNS)-mediated osteoblast suppression. Because the
      orientation of HSPCs in their osteoblastic niche is reported to be guided by
      [Ca(2+)], we speculated on a cooperation between the calcium-regulating hormones
      and SNS in the regulation of HSPC trafficking. Here, we present the severe
      impairment of granulocyte colony-stimulating factor-induced osteoblast
      suppression and subsequent HSPC mobilization in vitamin D receptor (VDR)
      deficient mice. In osteoblasts, functional VDR possessing, at least in part, a
      transcriptional activity, was specifically induced by beta2-adrenergic receptor
      (AR) agonists. While beta2-AR agonists transiently increased mRNA expression of
      Vdr and its downstream gene, Rankl, 1alpha,25-dihydroxyvitamin-D(3) sustained the
      beta2-AR-induced Rankl expression at high level by stabilizing VDR protein. These
      data suggest that VDR is essential for durable beta2-AR signaling in the stem
      cell niche. Our study demonstrates not only a novel function of VDR as a critical
      modulator of HSPC trafficking, but also the presence of a SNS-mediated, bone
      remodeling mechanism through VDR. VDR contributes to brain-bone-blood integration
      in an unanticipated way distinct from other classical calcium-regulating
      hormones.

PMID- 20813900
TI  - A role for proapoptotic Bax and Bak in T-cell differentiation and transformation.
AB  - Proapoptotic Bax and Bak are the key B-cell lymphoma-2 family members mediating
      apoptosis through the intrinsic pathway. Cells doubly deficient for Bax and Bak
      are profoundly resistant to apoptotic stimuli originating from multiple stimuli.
      Here we describe mice in which Bax and Bak have been deleted specifically in T
      cells using Lck-Cre. In these T cell-specific BaxBak-deficient mice, early T-cell
      progenitors accumulate in the thymus, with relative depletion of more mature T
      cells. In addition, bone marrow progenitor cells fail to progress to the double
      positive stage when cultured on OP9 stromal cells expressing the Notch ligand
      Delta-like 1, consistent with a critical role for Bax and Bak in early T-cell
      development. Over time, T cell-specific BaxBak-deficient mice progress to an
      aggressive T-cell lymphoblastic leukemia/lymphoma. Interestingly, quantitative
      real-time polymerase chain reaction analysis of BaxBak-deficient T-cell lymphomas
      does not display amplification of the Notch signal transduction pathway, commonly
      activated in T-cell leukemia in both mouse and man. Bax and Bak, key regulators
      of the intrinsic pathway of apoptosis, are thus required to prevent T-cell
      malignancy, and for normal T-cell differentiation, regulating early T-cell
      development at the stage of early T-lineage progenitor cells.

PMID- 20813902
TI  - Antivascular combo therapy: up-and-coming.

PMID- 20813901
TI  - PtdIns3P and Rac direct the assembly of the NADPH oxidase on a novel, pre
      phagosomal compartment during FcR-mediated phagocytosis in primary mouse
      neutrophils.
AB  - The generation of reactive oxygen species (ROS) by the nicotinamide adenine
      dinucleotide phosphate oxidase is an important mechanism by which neutrophils
      kill pathogens. The oxidase is composed of a membrane-bound cytochrome and 4
      soluble proteins (p67(phox), p40(phox), p47(phox), and GTP-Rac). These components
      form an active complex at the correct time and subcellular location through a
      series of incompletely understood mutual interactions, regulated, in part, by
      GTP/GDP exchange on Rac, protein phosphorylation, and binding to lipid
      messengers. We have used a variety of assays to follow the spatiotemporal
      assembly of the oxidase in genetically engineered primary mouse neutrophils,
      during phagocytosis of both serum- and immunoglobulin G-opsonized targets. The
      oxidase assembles directly on serum-Staphylococcus aureus-containing phagosomes
      within seconds of phagosome formation; this process is only partially dependent
      (~ 30%) on PtdIns3P binding to p40(phox), but totally dependent on Rac1/2 binding
      to p67(phox). In contrast, in response to immunoglobulin G-targets, the oxidase
      first assembles on a tubulovesicular compartment that develops at sites of
      granule fusion to the base of the emerging phagosome; oxidase assembly and
      activation is highly dependent on both PtdIns3P-p40(phox) and Rac2-p67(phox)
      interactions and delivery to the phagosome is regulated by Rab27a. These results
      define a novel pathway for oxidase assembly downstream of FcR-activation.

PMID- 20813903
TI  - Balancing act for elderly myeloma.

PMID- 20813904
TI  - JAK2 impairs stem cell function?

PMID- 20813905
TI  - NOX-free inflammasome activation.

PMID- 20813906
TI  - Sometimes a cigar is just a cigar.

PMID- 20813907
TI  - Comparative analysis of pistil transcriptomes reveals conserved and novel genes
      expressed in dry, wet, and semidry stigmas.
AB  - Fertilization in angiosperms depends on a complex cellular "courtship" between
      haploid pollen and diploid pistil. These pollen-pistil interactions are regulated
      by a diversity of molecules, many of which remain to be identified and
      characterized. Thus, it is unclear to what extent these processes are conserved
      among angiosperms, a fact confounded by limited sampling across taxa. Here, we
      report the analysis of pistil-expressed genes in Senecio squalidus (Asteraceae),
      a species from euasterid II, a major clade for which there are currently no data
      on pistil-expressed genes. Species from the Asteraceae characteristically have a
      "semidry stigma," intermediate between the "wet" and "dry" stigmas typical of the
      majority of angiosperms. Construction of pistil-enriched cDNA libraries for S.
      squalidus allowed us to address two hypotheses: (1) stigmas of S. squalidus will
      express genes common to wet and dry stigmas and genes specific to the semidry
      stigma characteristic of the Asteraceae; and (2) genes potentially essential for
      pistil function will be conserved between diverse angiosperm groups and therefore
      common to all currently available pistil transcriptome data sets, including S.
      squalidus. Our data support both these hypotheses. The S. squalidus pistil
      transcriptome contains novel genes and genes previously identified in pistils of
      species with dry stigmas and wet stigmas. Comparative analysis of the five pistil
      transcriptomes currently available (Oryza sativa, Crocus sativus, Arabidopsis
      thaliana, Nicotiana tabacum, and S. squalidus), representing four major
      angiosperm clades and the three stigma states, identified novel genes and
      conserved genes potentially regulating pollen-pistil interaction pathways common
      to monocots and eudicots.

PMID- 20813908
TI  - Nucleus-independent control of the rubisco operon by the plastid-encoded
      transcription factor Ycf30 in the red alga Cyanidioschyzon merolae.
AB  - Chloroplasts originated from a cyanobacterium, which was engulfed by a primitive
      eukaryotic host cell. During evolution, chloroplasts have largely lost their
      autonomy due to the loss of many genes from their own genomes. Consequently,
      expression of genes encoded in the chloroplast genome is mainly controlled by the
      factors transferred from the cytosol to chloroplasts. However, chloroplast
      genomes of glaucophytes and red algae have retained some transcription factors
      (hypothetical chloroplast open reading frame 27 to 30 [Ycf27-Ycf30]) that are
      absent from green algae and land plants. Here, we show that the red algal
      chloroplast up-regulates transcription of the Rubisco operon rbcLS-cbbX via Ycf30
      independently of nuclear control. Light-induced transcriptional activation of the
      Rubisco operon was observed in chloroplasts isolated from the red alga
      Cyanidioschyzon merolae. The activation was suppressed by 3-(3,4-dichlorophenyl)
      1,1-dimethylurea. These results suggest that chloroplast autonomously regulates
      transcription of the Rubisco operon in response to the activation of
      photosynthesis driven by the light. Transcriptional activation of the Rubisco
      operon was specifically repressed by the addition of anti-Ycf30 antibodies.
      Furthermore, reduced NADP, ribulose-1,5-bisphosphate, and 3-phosphoglyceric acid
      triggered the up-regulation of Rubisco transcription in the dark, and the
      activation was dependent on Ycf30. Thus, red algal chloroplasts have retained a
      nucleus-independent transcriptional regulation of the Rubisco operon to respond
      to environmental changes. The autonomous system would have been necessary for the
      initial fixation of cyanobacterial photosynthesis in the ancient
      nonphotosynthetic eukaryotic host. It has remained functional in the red algal
      chloroplast over evolutionary time.

PMID- 20813909
TI  - FIBRILLIN4 is required for plastoglobule development and stress resistance in
      apple and Arabidopsis.
AB  - The fibrillins are a large family of chloroplast proteins that have been linked
      with stress tolerance and disease resistance. FIBRILLIN4 (FIB4) is found
      associated with the photosystem II light-harvesting complex, thylakoids, and
      plastoglobules, which are chloroplast compartments rich in lipophilic
      antioxidants. For this study, FIB4 expression was knocked down in apple (Malus 3
      domestica) using RNA interference. Plastoglobule osmiophilicity was decreased in
      fib4 knockdown (fib4 KD) tree chloroplasts compared with the wild type, while
      total plastoglobule number was unchanged. Compared with the wild type, net
      photosynthetic CO(2) fixation in fib4 KD trees was decreased at high light
      intensity but was increased at low light intensity. Furthermore, fib4 KD trees
      produced more anthocyanins than the wild type when transferred from low to high
      light intensity, indicating greater sensitivity to high light stress. Relative to
      the wild type, fib4 KD apples were more sensitive to methyl viologen and had
      higher superoxide levels during methyl viologen treatment. Arabidopsis
      (Arabidopsis thaliana) fib4 mutants and fib4 KD apples were more susceptible than
      their wild-type counterparts to the bacterial pathogens Pseudomonas syringae
      pathovar tomato and Erwinia amylovora, respectively, and were more sensitive to
      ozone-induced tissue damage. Following ozone stress, plastoglobule osmiophilicity
      decreased in wild-type apple and remained low in fib4 KD trees; total
      plastoglobule number increased in fib4 KD apples but not in the wild type. These
      results indicate that FIB4 is required for plastoglobule development and
      resistance to multiple stresses. This study suggests that FIB4 is involved in
      regulating plastoglobule content and that defective regulation of plastoglobule
      content leads to broad stress sensitivity and altered photosynthetic activity.

PMID- 20813911
TI  - COOH-terminal isoleucine of lysosome-associated membrane protein-1 is optimal for
      its efficient targeting to dense secondary lysosomes.
AB  - Lysosome-associated membrane protein-1 (LAMP-1) consists of a highly glycosylated
      luminal domain, a single-transmembrane domain and a short cytoplasmic tail that
      possesses a lysosome-targeting signal (GYQTI(382)) at the COOH terminus. It is
      hypothesized that the COOH-terminal isoleucine, I(382), could be substituted with
      any other bulky hydrophobic amino acid residue for LAMP-1 to exclusively localize
      in lysosomes. In order to test this hypothesis, we compared subcellular
      distribution of four substitution mutants with phenylalanine, leucine, methionine
      and valine at the COOH-terminus (termed I382F, I382L, I382M and I382V,
      respectively) with that of wild-type (WT)-LAMP-1. Double-labelled
      immunofluorescence analyses showed that these substitution mutants were localized
      as significantly to late endocytic organelles as WT-LAMP-1. However, the
      quantitative subcellular fractionation study revealed different distribution of
      WT-LAMP-1 and these four COOH-terminal mutants in late endosomes and dense
      secondary lysosomes. WT-LAMP-1 was accumulated three to six times more in the
      dense lysosomal fraction than the four mutants. The level of WT-LAMP-1 in late
      endosomal fraction was comparable to those of I382F, I382M and I382V. Conversely,
      I382L in the late endosomal fraction was approximately three times more abundant
      than WT-LAMP-1. These findings define the presence of isoleucine residue at the
      COOH-terminus of LAMP-1 as critical in governing its efficient delivery to
      secondary lysosomes and its ratio of lysosomes to late endosomes.

PMID- 20813910
TI  - Topographic studies of the GroEL-GroES chaperonin complex by chemical cross
      linking using diformyl ethynylbenzene: the power of high resolution electron
      transfer dissociation for determination of both peptide sequences and their
      attachment sites.
AB  - Many essential cellular processes depend upon the self-assembly of stable
      multiprotein entities. The architectures of the vast majority of these protein
      machines remain unknown because these structures are difficult to obtain by
      biophysical techniques alone. However, recent progress in defining the
      architecture of protein complexes has resulted from integrating information from
      all available biochemical and biophysical sources to generate computational
      models. Chemical cross-linking is a technique that holds exceptional promise
      toward achieving this goal by providing distance constraints that reflect the
      topography of protein complexes. Combined with the available structural data,
      these constraints can yield three-dimensional models of higher order molecular
      machines. However, thus far the utility of cross-linking has been thwarted by
      insufficient yields of cross-linked products and tandem mass spectrometry methods
      that are unable to unambiguously establish the identity of the covalently labeled
      peptides and their sites of modification. We report the cross-linking of amino
      moieties by 1,3-diformyl-5-ethynylbenzene (DEB) with analysis by high resolution
      electron transfer dissociation. This new reagent coupled with this new energy
      deposition technique addresses these obstacles by generating cross-linked
      peptides containing two additional sites of protonation relative to conventional
      cross-linking reagents. In addition to excellent coverage of sequence ions by
      electron transfer dissociation, DEB cross-linking produces gas-phase precursor
      ions in the 4+, 5+, or 6+ charge states that are readily segregated from
      unmodified and dead-end modified peptides using charge-dependent precursor
      selection of only quadruply and higher charge state ions. Furthermore, electron
      transfer induces dissociation of the DEB-peptide bonds to yield diagnostic ion
      signals that reveal the "molecular ions" of the unmodified peptides. We
      demonstrate the power of this strategy by cross-linking analysis of the 21
      protein, ADP-bound GroEL-GroES chaperonin complex. Twenty-five unique sites of
      cross-linking were determined.

PMID- 20813913
TI  - Role of microsomal prostaglandin E synthase-1 in the facilitation of angiogenesis
      and the healing of gastric ulcers.
AB  - The importance of prostaglandin E(2) in various pathophysiological events
      emphasizes the necessity of understanding the role of PGE synthases (PGESs) in
      vivo. However, there has been no report on the functional relevance of microsomal
      PGES-1 (mPGES-1) to the physiological healing processes of gastric ulcers, or to
      angiogenesis, which is indispensable to the healing processes. In this report, we
      tested whether mPGES-1 plays a role in the healing of gastric ulcers and in the
      enhancement of angiogenesis using mPGES-1 knockout mice (mPGES-1 KO mice) and
      their wild-type (WT) counterparts. Gastric ulcers were induced by the serosal
      application of 100% acetic acid, and the areas of the ulcers were measured
      thereafter. mPGES-1 together with cyclooxygenase-2 were induced in the
      granulation tissues compared with normal stomach tissues. The healing of acetic
      acid-induced ulcers was significantly delayed in mPGES-1 KO mice compared with
      WT. This was accompanied with reduced angiogenesis in ulcer granulation tissues,
      as estimated by CD31 mRNA levels determined by real-time PCR and the microvessel
      density in granulation tissues. The mRNA levels of proangiogenic growth factors,
      such as transforming growth factor-beta, basic fibroblast growth factor, and
      connective tissue growth factor in ulcer granulation tissues determined were
      reduced in mPGES-1 KO mice compared with WT. The present results suggest that
      mPGES-1 enhances the ulcer-healing processes and the angiogenesis indispensable
      to ulcer healing, and that a selective mPGES-1 inhibitor should be used with care
      in patients with gastric ulcers.

PMID- 20813914
TI  - Role of EP4 receptor and prostaglandin transporter in prostaglandin E2-induced
      alteration in colonic epithelial barrier integrity.
AB  - Prostaglandin E(2) (PGE(2)) is a proinflammatory lipid mediator produced in
      excess in inflammatory bowel disease (IBD). PGE(2) couples to and signals via
      four different E-prostanoid (EP) receptors, namely EP1, EP2, EP3, and EP4. In
      this study, we determined a role for PGE(2) and EP4 receptors in altering colonic
      epithelial barrier integrity. In healthy colonic mucosa, EP4 receptors were
      localized on apical plasma membrane of epithelial cells at the tip of mucosal
      folds, whereas, in patients with IBD and in rats with dextran sodium sulfate
      (DSS)-induced colitis, they were diffusely overexpressed throughout the mucosa.
      Similarly, expression of EP4 receptor was polarized in T84 colonic epithelial
      monolayer and mimics the normal epithelium. Apical exposure of T84 monolayer with
      high levels of PGE(2) decreased barrier integrity, which was abrogated by an EP4
      receptor antagonist. To reveal the mechanism of vectorial transport of basally
      produced PGE(2) toward apical EP4 receptors, we identified prostaglandin
      transporters (PGT) in human colonic epithelia. PGT were least expressed on
      epithelial cells at the colonic mucosal folds of control subjects but
      overexpressed in epithelial cells of patients with IBD or animals with DSS
      induced colitis. T84 monolayer also expressed PGT, which increased twofold
      following stimulation with TNF-alpha. Importantly, in T84 monolayer stimulated
      with TNF-alpha, there was a corresponding increase in the uptake and vectorial
      transport of (3)H-PGE(2) to the apical surface. Knockdown or pharmacological
      inhibition of PGT significantly decreased vectorial transport of (3)H-PGE(2).
      These studies unravel a mechanism whereby EP4 receptor and PGT play a role in
      PGE(2)-induced alteration of epithelial barrier integrity in colitis.

PMID- 20813912
TI  - Cytodifferentiation of the postnatal mouse stomach in normal and Huntingtin
      interacting protein 1-related-deficient mice.
AB  - Huntingtin-interacting protein 1-related (Hip1r) is highly expressed in gastric
      parietal cells, where it participates in vesicular trafficking associated with
      acid secretion. Hip1r-deficient mice have a progressive remodeling of the mucosa,
      including apoptotic loss of parietal cells, glandular hypertrophy, mucous cell
      metaplasia, and reduced numbers of zymogenic cells. In this study, we
      characterized gastric gland development in wild-type and Hip1r-deficient mice to
      define normal development, as well as the timing and sequence of the cellular
      transformation events in the mutant stomach. Postnatal (newborn to 8-wk-old)
      stomachs were examined by histological and gene expression analysis. At birth,
      gastric glands in wild-type and mutant mice were rudimentary and mature gastric
      epithelial cells were not apparent, although marker expression was detected for
      most cell lineages. Interestingly, newborns exhibited unusual cell types,
      including a novel surface cell filled with lipid and cells that coexpressed
      markers of mature mucous neck and zymogenic cells. Glandular morphogenesis
      proceeded rapidly in both genotypes, with gastric glands formed by weaning at 3
      wk of age. In the Hip1r-deficient stomach, epithelial cell remodeling developed
      in a progressive manner. Initially, in the perinatal stomach, cellular changes
      were limited to parietal cell apoptosis. Other epithelial cell changes, including
      apoptotic loss of zymogenic cells and expansion of metaplastic mucous cells,
      emerged several weeks later when the glands were morphologically mature. Thus,
      parietal cell loss appeared to be the initiating event in Hip1r-deficient mice,
      with secondary remodeling of the other gastric epithelial cells.

PMID- 20813915
TI  - Isolation of periportal, midlobular, and centrilobular rat liver sinusoidal
      endothelial cells enables study of zonated drug toxicity.
AB  - Many liver sinusoidal endothelial cell (LSEC)-dependent processes, including drug
      induced liver injury, ischemia-reperfusion injury, acute and chronic rejection,
      fibrosis, and the HELLP (hemolytic anemia, elevated liver enzymes, low platelet
      count) syndrome, may have a lobular distribution. Studies of the mechanism of
      this distribution would benefit from a reliable method to isolate LSEC
      populations from different regions. We established and verified a simple method
      to isolate periportal, midlobular, and centrilobular LSEC. Three subpopulations
      of LSEC were isolated by immunomagnetic separation on the basis of CD45
      expression. Flow cytometry showed that 78.2 +/- 2.3% of LSEC were CD45 positive
      and that LSEC could be divided into CD45 bright (28.6 +/- 2.7% of total
      population), dim (49.6 +/- 1.0%), and negative populations (21.8 +/- 2.3%).
      Immunohistochemistry confirmed that in vivo expression of CD45 in LSEC had a
      lobular distribution with enhanced CD45 staining in periportal LSEC. Cell
      diameter, fenestral diameter, number of fenestrae per sieve plate and per cell,
      porosity, and lectin uptake were significantly different in the subpopulations,
      consistent with the literature. Endocytosis of low concentrations of the LSEC
      specific substrate, formaldehyde-treated serum albumin, was restricted to CD45
      bright and dim LSEC. Acetaminophen was more toxic to the CD45 dim and negative
      populations than to the CD45 bright population. In conclusion, CD45 is highly
      expressed in periportal LSEC, low in midlobular LSEC, and negative in
      centrilobular LSEC, and this provides an easy separation method to isolate LSEC
      from the three different hepatic regions. The LSEC subpopulations obtained by
      this method are adequate for functional studies and drug toxicity testing.

PMID- 20813916
TI  - Epigenetics of programmed obesity: alteration in IUGR rat hepatic IGF1 mRNA
      expression and histone structure in rapid vs. delayed postnatal catch-up growth.
AB  - Maternal food restriction (FR) during pregnancy results in intrauterine growth
      restricted (IUGR) offspring that show rapid catch-up growth and develop metabolic
      syndrome and adult obesity. However, continued nutrient restriction during
      nursing delays catch-up growth and prevents development of obesity. Epigenetic
      regulation of IGF1, which modulates growth and is synthesized and secreted by the
      liver, may play a role in the development of these morbidities. Control (AdLib)
      pregnant rats received ad libitum food through gestation and lactation, and FR
      dams were exposed to 50% food restriction from days 10 to 21. FR pups were nursed
      by either ad libitum-fed control dams (FR/AdLib) or FR dams (FR/FR). All pups
      were weaned to ad libitum feed. Maternal FR resulted in IUGR newborns with
      significantly lower liver weight and, with the use of chromatin
      immunoprecipitation, decreased dimethylation at H3K4 in the IGF1 region was
      observed. Obese adult FR/AdLib males had decreased dimethylation and increased
      trimethylation of H3K4 in the IGF1 region. This corresponded to an increase in
      mRNA expression of IGF1-A (134 +/- 5%), IGF1-B (165 +/- 6%), IGF1 exon 1 (149 +/-
      6%), and IGF1 exon 2 (146 +/- 7%) in the FR/AdLib compared with the AdLib/AdLib
      control group. In contrast, nonobese FR/FR had significantly higher IGF1-B mRNA
      levels (147 +/- 19%) than controls with no difference in IGF1-A, exon 1 or exon
      2. Modulation of the rate of IUGR newborn catch-up growth may thus protect
      against IGF1 epigenetic modifications and, consequently, obesity and associated
      metabolic abnormalities.

PMID- 20813917
TI  - Midregional pro-atrial natriuretic peptide for the diagnosis of cardiac-related
      dyspnea according to renal function in the emergency department: a comparison
      with B-type natriuretic peptide (BNP) and N-terminal proBNP.
AB  - BACKGROUND: Although renal dysfunction influences the threshold values of B-type
      natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in diagnosis of
      cardiac-related dyspnea (CRD), its effects on midregional pro-atrial natriuretic
      peptide (MR-proANP) threshold values are unknown. We evaluated the impact of
      renal function on MR-proANP concentrations and compared our results to those of
      BNP and NT-proBNP. METHODS: MR-proANP, BNP, and NT-proBNP concentrations were
      measured in blood samples collected routinely from dyspneic patients admitted to
      the emergency department. Patients were subdivided into tertiles based on their
      estimated glomerular filtration rate [eGFR, in mL . min(-1) . (1.73 m(2))(-1)]:
      tertiles 1 (<44.3), 2 (44.3-58.5), and 3 (>=58.6). RESULTS: Of 378 patients
      studied, 69% (n = 260) had impaired renal function [<60 mL . min(-1) . (1.73
      m(2))(-1)] and 30% (n = 114) had CRD. MR-proANP, BNP, and NT-proBNP
      concentrations were significantly increased in patients with impaired renal
      function. In each tertile, all peptides remained significantly increased in CRD
      patients by comparison with non-CRD patients. By ROC analysis, MR-proANP, BNP,
      and NT-proBNP threshold values for the diagnosis of CRD increased as eGFR
      decreased from tertile 3 to tertile 1. Areas under the ROC curve for all peptides
      were significantly lower in tertile 1. Using adapted thresholds, MR-proANP, BNP,
      and NT-proBNP remained independently predictive of CRD, even in tertile 1
      patients. CONCLUSIONS: Renal function influences optimum cutoff points of MR
      proANP for the diagnosis of CRD. With use of an optimum threshold value adapted
      to the eGFR category, MR-proANP remains as effective as BNP and NT-proBNP in
      independently predicting a diagnosis of CRD in the emergency department.

PMID- 20813918
TI  - The genetic and molecular basis for sunscreen biosynthesis in cyanobacteria.
AB  - Ultraviolet UV-A and UV-B radiation is harmful to living systems, causing damage
      to biological macromolecules. An important strategy for dealing with UV exposure
      is the biosynthesis of small-molecule sunscreens. Among such metabolites, the
      mycosporine and mycosporine-like amino acids (MAAs) are remarkable for their wide
      phylogenetic distribution and their unique chemical structures. Here, we report
      the identification of a MAA biosynthetic gene cluster in a cyanobacterium and the
      discovery of analogous pathways in other sequenced organisms. We have expressed
      the cluster in a heterologous bacterial host and characterized all four
      biosynthetic enzymes in vitro. In addition to clarifying the origin of the MAAs,
      these efforts have revealed two unprecedented enzymatic strategies for imine
      formation.

PMID- 20813919
TI  - A critical role for LTA4H in limiting chronic pulmonary neutrophilic
      inflammation.
AB  - Leukotriene A(4) hydrolase (LTA(4)H) is a proinflammatory enzyme that generates
      the inflammatory mediator leukotriene B(4) (LTB(4)). LTA(4)H also possesses
      aminopeptidase activity with unknown substrate and physiological importance; we
      identified the neutrophil chemoattractant proline-glycine-proline (PGP) as this
      physiological substrate. PGP is a biomarker for chronic obstructive pulmonary
      disease (COPD) and is implicated in neutrophil persistence in the lung. In acute
      neutrophil-driven inflammation, PGP was degraded by LTA(4)H, which facilitated
      the resolution of inflammation. In contrast, cigarette smoke, a major risk factor
      for the development of COPD, selectively inhibited LTA(4)H aminopeptidase
      activity, which led to the accumulation of PGP and neutrophils. These studies
      imply that therapeutic strategies inhibiting LTA(4)H to prevent LTB(4) generation
      may not reduce neutrophil recruitment because of elevated levels of PGP.

PMID- 20813921
TI  - Observing supernova 1987A with the refurbished Hubble Space Telescope.
AB  - Observations with the Hubble Space Telescope (HST), conducted since 1990, now
      offer an unprecedented glimpse into fast astrophysical shocks in the young
      remnant of supernova 1987A. Comparing observations taken in 2010 with the use of
      the refurbished instruments on HST with data taken in 2004, just before the Space
      Telescope Imaging Spectrograph failed, we find that the Lyalpha and Halpha lines
      from shock emission continue to brighten, whereas their maximum velocities
      continue to decrease. We observe broad, blueshifted Lyalpha, which we attribute
      to resonant scattering of photons emitted from hot spots on the equatorial ring.
      We also detect N v lambdalambda1239, 1243 angstrom line emission, but only to the
      red of Lyalpha. The profiles of the N v lines differ markedly from that of
      Halpha, suggesting that the N4+ ions are scattered and accelerated by turbulent
      electromagnetic fields that isotropize the ions in the collisionless shock.

PMID- 20813920
TI  - Piezo1 and Piezo2 are essential components of distinct mechanically activated
      cation channels.
AB  - Mechanical stimuli drive many physiological processes, including touch and pain
      sensation, hearing, and blood pressure regulation. Mechanically activated (MA)
      cation channel activities have been recorded in many cells, but the responsible
      molecules have not been identified. We characterized a rapidly adapting MA
      current in a mouse neuroblastoma cell line. Expression profiling and RNA
      interference knockdown of candidate genes identified Piezo1 (Fam38A) to be
      required for MA currents in these cells. Piezo1 and related Piezo2 (Fam38B) are
      vertebrate multipass transmembrane proteins with homologs in invertebrates,
      plants, and protozoa. Overexpression of mouse Piezo1 or Piezo2 induced two
      kinetically distinct MA currents. Piezos are expressed in several tissues, and
      knockdown of Piezo2 in dorsal root ganglia neurons specifically reduced rapidly
      adapting MA currents. We propose that Piezos are components of MA cation
      channels.

PMID- 20813922
TI  - A new mixing diagnostic and Gulf oil spill movement.
AB  - Chaotic advection has served as the paradigm for mixing in fluid flows with
      simple time dependence. Its skeletal structure is based on analysis of invariant
      attracting and repelling manifolds in fluid flows. Here we develop a finite-time
      theory for two-dimensional incompressible fluid flows with arbitrary time
      dependence and introduce a new mixing diagnostic based on it. Besides stretching
      events around attracting and repelling manifolds, this allows us to detect
      hyperbolic mixing zones. We used the new diagnostic to forecast the spatial
      location and timing of oil washing ashore in Plaquemines Parish and Grand Isle,
      Louisiana, and Pensacola, Florida, in May 2010 and the flow of oil toward Panama
      City Beach, Florida, in June 2010.

PMID- 20813923
TI  - China's research culture.

PMID- 20813924
TI  - Embryonic stem cells. Controversial ruling throws U.S. research into a tailspin.

PMID- 20813925
TI  - Climate change. Panel faults IPCC leadership but praises its conclusions.

PMID- 20813926
TI  - Antarctica. In ground-based astronomy's final frontier, China aims for new
      heights.

PMID- 20813928
TI  - Energy innovation. Novel grant promises greener buildings, regional growth.

PMID- 20813930
TI  - Newsmaker interview: Frank Gannon. Ireland's departing research chief on Irish
      and European science. Interview by John Travis.

PMID- 20813931
TI  - Mammoth-killer impact flunks out.

PMID- 20813932
TI  - Profile: Francois Nosten. The dour Frenchman on malaria's frontier.

PMID- 20813933
TI  - Astrophysics. An unsettled debate about the chemistry of the sun.

PMID- 20813934
TI  - Methane from the East Siberian Arctic Shelf.

PMID- 20813935
TI  - Give beach ecosystems their day in the sun.

PMID- 20813938
TI  - Candidate gene approach's missing link.

PMID- 20813939
TI  - Science education. Growing roles for science education in community colleges.

PMID- 20813940
TI  - Microbiology. Is the tide turning for new malaria medicines?

PMID- 20813941
TI  - Immunology. CAR'ing for the skin.

PMID- 20813942
TI  - Paleontology. Marine biodiversity dynamics over deep time.

PMID- 20813943
TI  - Chemistry. Just add water.

PMID- 20813944
TI  - Transcription. Targeting the core of transcription.

PMID- 20813945
TI  - Astronomy. Fullerenes and cosmic carbon.

PMID- 20813946
TI  - Heavy fermions and quantum phase transitions.
AB  - Quantum phase transitions arise in many-body systems because of competing
      interactions that promote rivaling ground states. Recent years have seen the
      identification of continuous quantum phase transitions, or quantum critical
      points, in a host of antiferromagnetic heavy-fermion compounds. Studies of the
      interplay between the various effects have revealed new classes of quantum
      critical points and are uncovering a plethora of new quantum phases. At the same
      time, quantum criticality has provided fresh insights into the electronic,
      magnetic, and superconducting properties of the heavy-fermion metals. We review
      these developments, discuss the open issues, and outline some directions for
      future research.

PMID- 20813947
TI  - Chlorine isotope fractionation in the stratosphere.
AB  - Chlorinated organic compounds are important contributors to the anthropogenic
      enhancement of stratospheric ozone depletion. We report measurements of
      stratospheric isotope fractionation in such a compound. Stratospheric and
      tropospheric difluorodichloromethane (CF2Cl2) were found to have the largest
      relative 37Cl/35Cl isotope ratio difference ever measured for a natural compound.
      The increase of the relative isotope ratio difference with altitude was tightly
      correlated to the corresponding decrease in the CF2Cl2 mixing ratio. The observed
      relationship has a high potential to provide new insights into atmospheric
      chemistry and transport processes.

PMID- 20813949
TI  - Real-time dynamics of single vortex lines and vortex dipoles in a Bose-Einstein
      condensate.
AB  - Understanding the behavior of quantized vortices is essential to gaining insight
      into diverse superfluid phenomena, from critical-current densities in
      superconductors to quantum turbulence in superfluids. We observe the real-time
      dynamics of quantized vortices in trapped dilute-gas Bose-Einstein condensates by
      repeatedly imaging the vortex cores. The precession frequency of a single vortex
      is measured by explicitly observing its time dependence and is found to be in
      good agreement with theory. We further characterize the dynamics of vortex
      dipoles in two distinct configurations: (i) an asymmetric configuration, in which
      the vortex trajectories are dynamic and nontrivial, and (ii) a stable, symmetric
      configuration, in which the dipole is stationary.

PMID- 20813948
TI  - Spiroindolones, a potent compound class for the treatment of malaria.
AB  - Recent reports of increased tolerance to artemisinin derivatives--the most
      recently adopted class of antimalarials--have prompted a need for new treatments.
      The spirotetrahydro-beta-carbolines, or spiroindolones, are potent drugs that
      kill the blood stages of Plasmodium falciparum and Plasmodium vivax clinical
      isolates at low nanomolar concentration. Spiroindolones rapidly inhibit protein
      synthesis in P. falciparum, an effect that is ablated in parasites bearing
      nonsynonymous mutations in the gene encoding the P-type cation-transporter
      ATPase4 (PfATP4). The optimized spiroindolone NITD609 shows pharmacokinetic
      properties compatible with once-daily oral dosing and has single-dose efficacy in
      a rodent malaria model.

PMID- 20813950
TI  - Graphene visualizes the first water adlayers on mica at ambient conditions.
AB  - The dynamic nature of the first water adlayers on solid surfaces at room
      temperature has made the direct detection of their microscopic structure
      challenging. We used graphene as an atomically flat coating for atomic force
      microscopy to determine the structure of the water adlayers on mica at room
      temperature as a function of relative humidity. Water adlayers grew epitaxially
      on the mica substrate in a layer-by-layer fashion. Submonolayers form atomically
      flat, faceted islands of height 0.37 +/- 0.02 nanometers, in agreement with the
      height of a monolayer of ice. The second adlayers, observed at higher relative
      humidity, also appear icelike, and thicker layers appear liquidlike. Our results
      also indicate nanometer-scale surface defects serve as nucleation centers for the
      formation of both the first and the second adlayers.

PMID- 20813951
TI  - The shifting balance of diversity among major marine animal groups.
AB  - The fossil record demonstrates that each major taxonomic group has a consistent
      net rate of diversification and a limit to its species richness. It has been
      thought that long-term changes in the dominance of major taxonomic groups can be
      predicted from these characteristics. However, new analyses show that diversity
      limits may rise or fall in response to adaptive radiations or extinctions. These
      changes are idiosyncratic and occur at different times in each taxa. For example,
      the end-Permian mass extinction permanently reduced the diversity of important,
      previously dominant groups such as brachiopods and crinoids. The current global
      crisis may therefore permanently alter the biosphere's taxonomic composition by
      changing the rules of evolution.

PMID- 20813952
TI  - The spread of behavior in an online social network experiment.
AB  - How do social networks affect the spread of behavior? A popular hypothesis states
      that networks with many clustered ties and a high degree of separation will be
      less effective for behavioral diffusion than networks in which locally redundant
      ties are rewired to provide shortcuts across the social space. A competing
      hypothesis argues that when behaviors require social reinforcement, a network
      with more clustering may be more advantageous, even if the network as a whole has
      a larger diameter. I investigated the effects of network structure on diffusion
      by studying the spread of health behavior through artificially structured online
      communities. Individual adoption was much more likely when participants received
      social reinforcement from multiple neighbors in the social network. The behavior
      spread farther and faster across clustered-lattice networks than across
      corresponding random networks.

PMID- 20813953
TI  - Human-restricted bacterial pathogens block shedding of epithelial cells by
      stimulating integrin activation.
AB  - Colonization of mucosal surfaces is the key initial step in most bacterial
      infections. One mechanism protecting the mucosa is the rapid shedding of
      epithelial cells, also termed exfoliation, but it is unclear how pathogens
      counteract this process. We found that carcinoembryonic antigen (CEA)-binding
      bacteria colonized the urogenital tract of CEA transgenic mice, but not of wild
      type mice, by suppressing exfoliation of mucosal cells. CEA binding triggered de
      novo expression of the transforming growth factor receptor CD105, changing focal
      adhesion composition and activating beta1 integrins. This manipulation of
      integrin inside-out signaling promotes efficient mucosal colonization and
      represents a potential target to prevent or cure bacterial infections.

PMID- 20813954
TI  - The junctional adhesion molecule JAML is a costimulatory receptor for epithelial
      gammadelta T cell activation.
AB  - Gammadelta T cells present in epithelial tissues provide a crucial first line of
      defense against environmental insults, including infection, trauma, and
      malignancy, yet the molecular events surrounding their activation remain poorly
      defined. Here we identify an epithelial gammadelta T cell-specific costimulatory
      molecule, junctional adhesion molecule-like protein (JAML). Binding of JAML to
      its ligand Coxsackie and adenovirus receptor (CAR) provides costimulation leading
      to cellular proliferation and cytokine and growth factor production. Inhibition
      of JAML costimulation leads to diminished gammadelta T cell activation and
      delayed wound closure akin to that seen in the absence of gammadelta T cells. Our
      results identify JAML as a crucial component of epithelial gammadelta T cell
      biology and have broader implications for CAR and JAML in tissue homeostasis and
      repair.

PMID- 20813955
TI  - The molecular interaction of CAR and JAML recruits the central cell signal
      transducer PI3K.
AB  - Coxsackie and adenovirus receptor (CAR) is the primary cellular receptor for
      group B coxsackieviruses and most adenovirus serotypes and plays a crucial role
      in adenoviral gene therapy. Recent discovery of the interaction between
      junctional adhesion molecule-like protein (JAML) and CAR uncovered important
      functional roles in immunity, inflammation, and tissue homeostasis. Crystal
      structures of JAML ectodomain (2.2 angstroms) and its complex with CAR (2.8
      angstroms) reveal an unusual immunoglobulin-domain assembly for JAML and a
      charged interface that confers high specificity. Biochemical and mutagenesis
      studies illustrate how CAR-mediated clustering of JAML recruits phosphoinositide
      3-kinase (P13K) to a JAML intracellular sequence motif as delineated for the
      alphabeta T cell costimulatory receptor CD28. Thus, CAR and JAML are cell
      signaling receptors of the immune system with implications for asthma, cancer,
      and chronic nonhealing wounds.

PMID- 20813957
TI  - Proteomic analyses identify a diverse array of nuclear processes affected by
      small ubiquitin-like modifier conjugation in Arabidopsis.
AB  - The covalent attachment of SUMO (small ubiquitin-like modifier) to other
      intracellular proteins affects a broad range of nuclear processes in yeast and
      animals, including chromatin maintenance, transcription, and transport across the
      nuclear envelope, as well as protects proteins from ubiquitin addition.
      Substantial increases in SUMOylated proteins upon various stresses have also
      implicated this modification in the general stress response. To help understand
      the role(s) of SUMOylation in plants, we developed a stringent method to isolate
      SUMO-protein conjugates from Arabidopsis thaliana that exploits a tagged SUMO1
      variant that faithfully replaces the wild-type protein. Following purification
      under denaturing conditions, SUMOylated proteins were identified by tandem mass
      spectrometry from both nonstressed plants and those exposed to heat and oxidative
      stress. The list of targets is enriched for factors that direct SUMOylation and
      for nuclear proteins involved in chromatin remodeling/repair, transcription, RNA
      metabolism, and protein trafficking. Targets of particular interest include
      histone H2B, components in the LEUNIG/TOPLESS corepressor complexes, and proteins
      that control histone acetylation and DNA methylation, which affect genome-wide
      transcription. SUMO attachment site(s) were identified in a subset of targets,
      including SUMO1 itself to confirm the assembly of poly-SUMO chains. SUMO1 also
      becomes conjugated with ubiquitin during heat stress, thus connecting these two
      posttranslational modifications in plants. Taken together, we propose that
      SUMOylation represents a rapid and global mechanism for reversibly manipulating
      plant chromosomal functions, especially during environmental stress.

PMID- 20813958
TI  - Distribution of resting and ligand-bound ErbB1 and ErbB2 receptor tyrosine
      kinases in living cells using number and brightness analysis.
AB  - Ligand-driven dimerizations of ErbB receptor subunits fulfill a fundamental role
      in their activation. We have used the number and brightness analysis technique to
      investigate the existence of preformed ligand-independent dimers and clusters and
      to characterize the initial steps in the activation of ErbB1 and ErbB2. In cells
      expressing 50,000-200,000 receptors, ErbB1 was monomeric in the absence of ligand
      stimulation, whereas in CHO cells with receptor levels >500,000 as much as 30% of
      ErbB1 was present as preformed dimers. EGF induced the formation of ErbB1 dimers
      as well as larger clusters (up to pentamers) that colocalized with clathrin
      coated pits. The distribution of unstimulated ErbB2 in cells expressing 3.10(5)
      10(6) receptors was fundamentally different, in that this receptor was present in
      preformed homoassociated aggregates containing 5-10 molecules. These constitutive
      ErbB2 homoclusters colocalized with caveolae, increased in size at
      subphysiological temperatures, but decreased in size upon EGF stimulation. We
      conclude that these ErbB2 clusters are promoted primarily by membrane-mediated
      interactions and are dispersed upon ligand stimulation.

PMID- 20813959
TI  - Neural inhibition enables selection during language processing.
AB  - Whether grocery shopping or choosing words to express a thought, selecting
      between options can be challenging, especially for people with anxiety. We
      investigate the neural mechanisms supporting selection during language processing
      and its breakdown in anxiety. Our neural network simulations demonstrate a
      critical role for competitive, inhibitory dynamics supported by GABAergic
      interneurons. As predicted by our model, we find that anxiety (associated with
      reduced neural inhibition) impairs selection among options and associated
      prefrontal cortical activity, even in a simple, nonaffective verb-generation
      task, and the GABA agonist midazolam (which increases neural inhibition) improves
      selection, whereas retrieval from semantic memory is unaffected when selection
      demands are low. Neural inhibition is key to choosing our words.

PMID- 20813960
TI  - Novel lipid mediators and resolution mechanisms in acute inflammation: to resolve
      or not?
AB  - Because inflammation is appreciated as a unifying basis of many widely occurring
      diseases, the mechanisms involved in its natural resolution are of considerable
      interest. Using contained, self-limited inflammatory exudates and a systems
      approach, novel lipid-derived mediators and pathways were uncovered in the
      resolution of inflammatory exudates. These new families of local mediators
      control both the duration and magnitude of acute inflammation as well as the
      return of the site to homeostasis in the process of catabasis. This new genus of
      specialized proresolving mediators (SPM) includes essential fatty acid-derived
      lipoxins, resolvins, protectins, and, most recently, maresins. These families
      were named based on their unique structures and potent stereoselective actions.
      The temporally initiated biosynthesis of SPM and their direct impact on leukocyte
      trafficking and macrophage-directed clearance mechanisms provide clear evidence
      that resolution is an active, programmed response at the tissue level. Moreover,
      SPM that possess anti-inflammatory (ie, limiting PMN infiltration) and
      proresolving (enhance macrophage uptake and clearance of apoptotic PMN and
      microbial particles) actions as well as stimulating mucosal antimicrobial
      responses demonstrate that anti-inflammation and proresolution are different
      responses of the host and novel defining properties of these molecules. The
      mapping of new resolution circuits has opened the possibility for understanding
      mechanisms that lead from acute to chronic inflammation, or to the resolution
      thereof, as well as to potential, resolution-based immunopharmacological
      therapies.

PMID- 20813961
TI  - Tuberin regulates E-cadherin localization: implications in epithelial-mesenchymal
      transition.
AB  - The tuberous sclerosis complex 2 (TSC2) gene encodes the protein tuberin, which
      functions as a key negative regulator of both mammalian target of rapamycin
      (mTOR) C1-dependent cell growth and proliferation. Loss-of-function mutations of
      TSC2 result in mTORC1 hyperactivity and predispose individuals to both tuberous
      sclerosis and lymphangioleiomyomatosis. These overlapping diseases have in common
      the abnormal proliferation of smooth muscle-like cells. Although the origin of
      these cells is unknown, accumulating evidence suggests that a metastatic
      mechanism may be involved, but the means by which the mTOR pathway contributes to
      this disease process remain poorly understood. In this study, we show that
      tuberin regulates the localization of E-cadherin via an Akt/mTORC1/CLIP170
      dependent, rapamycin-sensitive pathway. Consequently, Tsc2(-/-) epithelial cells
      display a loss of plasma membrane E-cadherin that leads to reduced cell-cell
      adhesion. Under confluent conditions, these cells detach, grow in suspension, and
      undergo epithelial-mesenchymal transition (EMT) that is marked by reduced
      expression levels of both E-cadherin and occludin and increased expression levels
      of both Snail and smooth muscle actin. Functionally, the Tsc2(-/-) cells
      demonstrate anchorage-independent growth, cell scattering, and anoikis
      resistance. Human renal angiomyolipomas and lymphangioleiomyomatosis also express
      markers of EMT and exhibit an invasive phenotype that can be interpreted as
      consistent with EMT. Together, these results suggest a novel relationship between
      TSC2/mTORC1 and the E-cadherin pathways and implicate EMT in the pathogenesis of
      tuberous sclerosis complex-related diseases.

PMID- 20813962
TI  - Increase in viral load, viral integration, and gain of telomerase genes during
      uterine cervical carcinogenesis can be simultaneously assessed by the HPV 16/18
      MLPA-assay.
AB  - Oncogenic human papillomavirus (HPV) infection is the most important risk factor
      in cervical carcinogenesis cases; high viral loads, viral integration into the
      host genome, and gain of the telomerase-related genes, TERT and TERC, are all
      factors associated with progression to cancer. A recently developed
      multiparameter HPV 16/18 multiplex ligation-dependent probe amplification (MLPA)
      assay, which allows the simultaneous assessment of these factors, was applied to
      a series of 67 normal and (pre)malignant frozen uterine cervical samples, as well
      as to 91 cytological preparations, to test the ability of the MLPA assay to
      identify high-risk lesions on the basis of these factors. Validation was
      performed using quantitative PCR, the PapilloCheck and fluorescence in situ
      hybridization. Only 5 out of 37 normal tissue samples or low-grade cervical
      lesions (ie, CIN1 and condyloma) showed either an HPV16 viral load higher than 25
      copies per cell, viral integration, and/or gain of one of the telomerase-related
      genes, whereas for the high-grade cervical lesions, one or more of these risk
      factors was found in 25 of 30 cases. The HPV MLPA assay showed a sensitivity of
      83% and a specificity of 86% in frozen cervical specimens. Furthermore, the
      feasibility of the MLPA assay was shown for cytological samples, where in 57% of
      high-grade squamous intraepithelial lesion cases, the high-risk factors were
      detected using this assay.

PMID- 20813963
TI  - Site-dependent E-cadherin cleavage and nuclear translocation in a metastatic
      colorectal cancer model.
AB  - Metastases are frequently found during colorectal cancer diagnoses and are the
      main determinants of clinical outcome. The lack of reliable models of metastases
      has precluded their mechanistic understanding and our capacity to improve
      outcome. We studied the effect of E-cadherin and Snail1 expression on
      metastagenesis in a colorectal cancer model. We microinjected SW480-ADH human
      colorectal cancer cells, transfected with an empty vector (Mock) or
      overexpressing Snail1 (Snail1(OE)) or E-cadherin (E-cadherin(OE)), in the ceca of
      nude mice (eight per group) and analyzed tumor growth, dissemination, and Snail1,
      E-cadherin, beta-catenin, and Presenilin1 (PS1) expression in local tumors and/or
      metastatic foci. Snail1(OE) cells disseminated only to lymph nodes, whereas Mock
      or E-cadherin(OE) cells spread to lymph nodes and peritoneums. Peritoneal tumor
      foci developed by E-cadherin(OE) cells presented an increase in E-cadherin
      proteolysis and nuclear translocation, and enhanced expression of proteolytically
      active PS1, which was linked to increased tumor growth and shortened mouse
      survival. Interestingly, local and lymph node tumors in mice bearing E
      cadherin(OE) cells overexpressed E-cadherin, but they did not show E-cadherin
      proteolysis or nuclear translocation. Remarkably, E-cadherin nuclear
      translocation and enhanced expression of active PS1 were found in a patient with
      colorectal signet-ring cell carcinoma. In conclusion, we have established a
      colorectal cancer metastasis model in which E-cadherin proteolyis and nuclear
      translocation associates with aggressive foci growth only in the peritoneal
      microenvironment.

PMID- 20813964
TI  - alphaB-crystallin is elevated in highly infiltrative apoptosis-resistant
      glioblastoma cells.
AB  - We have previously established two distinct glioma phenotypes by serial
      xenotransplantation of human glioblastoma (GBM) biopsies in nude rats. These
      tumors undergo a gradual transition from a highly invasive nonangiogenic to a
      less-invasive angiogenic phenotype. In a protein screen to identify molecular
      markers associated with the infiltrative phenotype, we identified alpha-basic
      crystallin (alphaBc), a small heat-shock protein with cytoprotective properties.
      Its increased expression in the infiltrative phenotype was validated by
      immunohistochemistry and Western blots, confirming its identity to be tumor
      derived and not from the host. Stereotactic human GBM biopsies taken from MRI
      defined areas verified stronger alphaBc expression in the infiltrative edge
      compared to the tumor core. Cell migration assays and immunofluorescence staining
      showed alphaBc to be expressed by migrating cells in vitro. To determine alphaBc
      function, we altered its expression levels. alphaBc siRNA depletion caused a loss
      of migrating tumor cells from biopsy spheroids and delayed monolayer wound
      closure. In contrast, glioma cell migration in a Boyden chamber assay was
      unaffected by either alphaBc knockdown or overexpression, indicating that alphaBc
      is not functionally linked to the cell migration machinery. However, after siRNA
      alphaBc depletion, a significant sensitization of cells to various apoptotic
      inducers was observed (actinomycin, tumor necrosis factor alpha, and TNF-related
      apoptosis-inducing ligand [TRAIL]). In conclusion, alphaBc is overexpressed by
      highly migratory glioma cells where it plays a functional role in apoptosis
      resistance.

PMID- 20813965
TI  - Adiponectin lowers glucose production by increasing SOGA.
AB  - Adiponectin is a hormone that lowers glucose production by increasing liver
      insulin sensitivity. Insulin blocks the generation of biochemical intermediates
      for glucose production by inhibiting autophagy. However, autophagy is stimulated
      by an essential mediator of adiponectin action, AMPK. This deadlock led to our
      hypothesis that adiponectin inhibits autophagy through a novel mediator. Mass
      spectrometry revealed a novel protein that we call suppressor of glucose by
      autophagy (SOGA) in adiponectin-treated hepatoma cells. Adiponectin increased
      SOGA in hepatocytes, and siRNA knockdown of SOGA blocked adiponectin inhibition
      of glucose production. Furthermore, knockdown of SOGA increased late
      autophagosome and lysosome staining and the secretion of valine, an amino acid
      that cannot be synthesized or metabolized by liver cells, suggesting that SOGA
      inhibits autophagy. SOGA decreased in response to AICAR, an activator of AMPK,
      and LY294002, an inhibitor of the insulin signaling intermediate, PI3K. AICAR
      reduction of SOGA was blocked by adiponectin; however, adiponectin did not
      increase SOGA during PI3K inhibition, suggesting that adiponectin increases SOGA
      through the insulin signaling pathway. SOGA contains an internal signal peptide
      that enables the secretion of a circulating fragment of SOGA, providing a
      surrogate marker for intracellular SOGA levels. Circulating SOGA increased in
      parallel with adiponectin and insulin activity in both humans and mice. These
      results suggest that adiponectin-mediated increases in SOGA contribute to the
      inhibition of glucose production.

PMID- 20813966
TI  - The physiological deadlock between AMPK and gluconeogenesis: SOGA, a novel
      protein, may provide the key.
AB  - This Commentary discusses how suppressor of glucose by autophagy (SOGA)
      contributes to adiponectin-mediated insulin-dependent inhibition of autophagy
      during the activation of adenosine monophosphate kinase (AMPK).

PMID- 20813967
TI  - Braak staging in mouse models of Alzheimer's disease.
AB  - In the present paper by David E. Hurtado and colleagues report on a new mouse
      model for AD bearing Abeta and MAPT pathology by crossing PS19 and PDAPP Tg mice.
      Here, we tried to highlight the importance and necessity of the critical and
      systematic analysis of models such as the Braak like staging in AD mouse models.

PMID- 20813968
TI  - Disparate cellular basis of improved liver repair in beta-catenin-overexpressing
      mice after long-term exposure to 3,5-diethoxycarbonyl-1,4-dihydrocollidine.
AB  - Administration of a hepatotoxic diet containing 0.1% 3,5-diethoxycarbonyl-1,4
      dihydrocollidine (DDC) induces biliary damage followed by hepatocyte injury,
      which is repaired through atypical ductular proliferation and oval cells and
      their subsequent differentiation to bile duct cells and hepatocytes. In this
      study, we examine whether excess beta-catenin in transgenic (TG) mice would
      provide any reparative advantage in response to DDC. No differences in appearance
      or numbers of total A6-positive oval cells were observed after DDC
      administration. However, an increase in A6-positive "atypical hepatocytes" in the
      TG livers was observed after 14 and 28 days, coinciding with an increase in
      proliferating cell nuclear antigen-positive hepatocytes. Intriguingly, after
      chronic DDC administration for 150 days, a further increase in atypical
      hepatocytes was evident in TG mice, with higher numbers of proliferating cell
      nuclear antigen-positive hepatocytes exhibiting cytoplasmic/nuclear beta-catenin
      and alpha-fetoprotein but not CK19, HNF1beta, or Trop-2. Coincidently, we
      observed an improvement in intrahepatic cholestasis as seen by decreases in both
      serum bilirubin and alkaline phosphatase levels in TG mice, indicating an overall
      improvement in hepatic repair. TG mice exposed to DDC for 4 weeks followed by 2
      days of normal chow showed decreases in alkaline phosphatase, atypical ductular
      proliferation, and periportal inflammation compared with wild-type animals,
      verifying improved biliary repair in TG livers. Thus, we report a potential role
      of beta-catenin in liver repair, especially in enhancing the resolution of
      intrahepatic cholestasis after DDC injury.

PMID- 20813969
TI  - Lin- cells mediate tissue repair by regulating MCP-1/CCL-2.
AB  - Exogenous bone marrow-derived cells (BMDCs) are promising therapeutic agents for
      the treatment of tissue ischemia and traumatic injury. However, until we identify
      the molecular mechanisms that underlie their actions, there can be no rational
      basis for the design of therapeutic strategies using BMDCs. The pro-healing
      effects of BMDCs are apparent very shortly after treatment, which suggests that
      they may exert their effects by the modulation of acute inflammation. We
      investigated this hypothesis by taking advantage of the fact that BMDCs from
      healthy, young, but not obese, diabetic mice stimulate vascular growth. By
      comparing both in vitro secretion and in vivo local induction of acute phase
      inflammatory cytokines by these cells, we identified monocyte chemoattractant
      factor 1 and tumor necrosis factor alpha as potential mediators of BMDC-induced
      tissue repair. In vivo analysis of BMDC-treated ischemic limbs and cutaneous
      wounds revealed that the production of monocyte chemoattractant factor 1 by
      exogenous and endogenous BMDCs is essential for BMDC-mediated vascular growth and
      tissue healing, while the inability of BMDCs to produce tumor necrosis factor
      alpha appears to play a lesser but still meaningful role. Thus, measurements of
      the secretion of cytokines by BMDCs may allow us to identify a priori individuals
      who would or would not be good candidates for BMDC-based therapies.

PMID- 20813970
TI  - PTEN, PIK3CA, p-AKT, and p-p70S6K status: association with trastuzumab response
      and survival in patients with HER2-positive metastatic breast cancer.
AB  - Phosphatase and tensin homolog (PTEN) is a key modulator of trastuzumab
      sensitivity in HER2-overexpressing breast cancer. Because PTEN opposes the
      downstream signaling of phosphoinositide 3-kinase (PI3K), we investigated the
      role of PTEN and other components of the PI3K pathway in trastuzumab resistance.
      We analyzed the status of PTEN, p-AKT-Ser473, and p-p70S6K-Thr389 using
      immunohistochemistry. PIK3CA mutation status was analyzed by direct sequencing.
      Primary tumor tissue was available from 137 patients with HER2-overexpressing
      metastatic breast cancer who had received trastuzumab-based chemotherapy. We
      observed that each of the four biomarkers alone did not significantly correlate
      with trastuzumab response, whereas PTEN loss alone significantly correlated with
      shorter survival times (P = 0.023). PI3K pathway activation, defined as PTEN loss
      and/or PIK3CA mutation, was associated with a poor response to trastuzumab (P =
      0.047) and a shorter survival time (P = 0.015). PTEN loss was significantly
      associated with a poor response to trastuzumab (P = 0.028) and shorter survival
      time (P = 0.008) in patients who had received first-line trastuzumab and in
      patients with estrogen receptor- (P = 0.029) and progesterone receptor-negative
      tumors (P = 0.033). p-AKT-Ser473 and p-p70S6K-Thr389 each had a limited
      correlation with trastuzumab response. When these markers were combined with PTEN
      loss, an increased correlation with patient outcome was observed. In conclusion,
      PI3K pathway activation plays a pivotal role in trastuzumab resistance. Our
      findings may facilitate the evaluation of tumor response to trastuzumab-based and
      targeted therapies.

PMID- 20813971
TI  - Role of ocular complement factor H in a murine model of choroidal
      neovascularization.
AB  - The objective of this study was to explore the relationship between local (ie,
      ocular) complement factor H (CFH) and choroidal neovascularization (CNV)
      associated with wet age-related macular degeneration (AMD), a leading cause of
      irreversible blindness, in laser-treated C57BL/6 mice. Immunohistochemical and RT
      PCR analysis of retinal pigmented epithelium (RPE)-choroid sclera revealed that
      the expression of CFH was down-regulated on day 1 with a dramatic increase on
      days 5 and 7 postlaser injury. Flat mount and Western blot analysis further
      revealed that membrane attack complex (MAC) expression was up-regulated on days 1
      and 3 postlaser injury; however, MAC was down-regulated on days 5 and 7
      postinjury but was still higher than in non-injured mice. Similar patterns for
      CFH and MAC were observed for RPE cells when serial paraffin sections of the
      laser spots were analyzed. Subretinal injection of siRNA directed against CFH
      resulted in a threefold suppression of CFH in the RPE and choroid without
      affecting either CFH levels in the liver or the functional activity of the
      alternative pathway in the peripheral blood. Ocular knock-down of CFH resulted in
      increased MAC deposition, which leads to the early onset as well as exacerbation
      of laser-induced CNV. In conclusion, our findings provide evidence that CFH
      present on RPE and choroid regulates local MAC formation that is critical for the
      development of laser-induced CNV.

PMID- 20813972
TI  - Rapid formation of extended processes and engagement of Theiler's virus-infected
      neurons by CNS-infiltrating CD8 T cells.
AB  - A fundamental question in neuroimmunology is the extent to which CD8 T cells
      actively engage virus-infected neurons. In the Theiler's murine encephalomyelitis
      virus (TMEV) model of multiple sclerosis, an effective central nervous system
      (CNS)-infiltrating antiviral CD8 T cell response offers protection from this
      demyelinating disease. However, the specific CNS cell types engaged by these
      protective CD8 T cells in TMEV-resistant strains remains unknown. We used
      confocal microscopy to visualize the morphology, migration, and specific cellular
      interactions between adoptively transferred CD8 T cells and specific CNS cell
      types. Adoptively transferred GFP+ CD8+ splenocytes migrated to the brain and
      became 93% specific for the immunodominant virus epitope D(b):VP2(121-130). These
      CD8 T cells also polarized T cell receptor, CD8 protein, and granzyme B toward
      target neurons. Furthermore, we observed CD8 T cells forming cytoplasmic
      processes up to 45 MUm in length. Using live tissue imaging, we determined that
      these T cell-extended processes (TCEPs) could be rapidly formed and were
      associated with migratory behavior through CNS tissues. These studies provide
      evidence that antiviral CD8 T cells have the capacity to engage virus-infected
      neurons in vivo and are the first to document and measure the rapid formation of
      TCEPs on these brain-infiltrating lymphocytes using live tissue imaging.

PMID- 20813973
TI  - No haploinsufficiency but loss of heterozygosity for EXT in multiple
      osteochondromas.
AB  - Multiple osteochondromas (MO) is an autosomal dominant disorder caused by
      germline mutations in EXT1 and/or EXT2. In contrast, solitary osteochondroma (SO)
      is nonhereditary. Products of the EXT gene are involved in heparan sulfate (HS)
      biosynthesis. In this study, we investigated whether osteochondromas arise via
      either loss of heterozygosity (2 hits) or haploinsufficiency. An in vitro three
      dimensional chondrogenic pellet model was used to compare heterozygous bone
      marrow-derived mesenchymal stem cells (MSCs EXT(wt/-)) of MO patients with normal
      MSCs and the corresponding tumor specimens (presumed EXT(-/-)). We demonstrated a
      second hit in EXT in five of eight osteochondromas. HS chain length and
      structure, in vitro chondrogenesis, and EXT expression levels were identical in
      both EXT(wt/-) and normal MSCs. Immunohistochemistry for HS, HS proteoglycans,
      and HS-dependent signaling pathways (eg, TGF-beta/BMP, Wnt, and PTHLH) also
      showed no differences. The cartilaginous cap of osteochondroma contained a
      mixture of HS-positive and HS-negative cells. Because a heterozygous EXT mutation
      does not affect chondrogenesis, EXT, HS, or downstream signaling pathways in
      MSCs, our results refute the haploinsufficiency theory. We found a second hit in
      63% of analyzed osteochondromas, supporting the hypothesis that osteochondromas
      arise via loss of heterozygosity. The detection of the second hit may depend on
      the ratio of HS-positive (normal) versus HS-negative (mutated) cells in the
      cartilaginous cap of the osteochondroma.

PMID- 20813974
TI  - Allometry of the mammalian intracellular pulmonary surfactant system.
AB  - Alveolar epithelial (AE) surface area is closely correlated with body mass (BM)
      in mammals. The AE is covered by a surfactant layer produced by alveolar
      epithelial type II (AE2) cells. We hypothesized that the total number of AE2
      cells and the volume of intracellular surfactant-storing lamellar bodies (Lb) are
      correlated with BM with a similar slope as AE surface area. We used light and
      electron microscopic stereology to estimate the number and mean volume of AE2
      cells and the total volume of Lb in 12 mammalian species ranging from 2 to 3 g
      (Etruscan shrew) to 400-500 kg (horse) BM. The mean size of Lb was evaluated
      using the volume-weighted mean volume and the volume-to-surface ratio of Lb. The
      mean volume of AE2 cells was 500-600 MUm(3) in most species, but was higher in
      Etruscan shrew, guinea pig, and human lung. The mean volume of Lb per AE2 cell
      was 80-100 MUm(3) in most species, with the same exceptions as above. However,
      the total number of AE2 cells and the total volume of Lb were closely correlated
      with BM and exhibited an allometric relationship similar to the slope of AE
      surface area. The mean size of Lb was similar in all investigated species. In
      conclusion, the mean volume of AE2 cells and their Lb are independent of BM but
      show some interspecific variations. The adaptation of the intracellular
      surfactant pool size to BM is obtained by the variation of the number of AE2
      cells in the lung.

PMID- 20813975
TI  - High incidence of venous and arterial gas emboli at rest after trimix diving
      without protocol violations.
AB  - SCUBA diving is associated with generation of gas emboli due to gas release from
      the supersaturated tissues during decompression. Gas emboli arise mostly on the
      venous side of circulation, and they are usually eliminated as they pass through
      the lung vessels. Arterialization of venous gas emboli (VGE) is seldom reported,
      and it is potentially related to neurological damage and development of
      decompression sickness. The goal of the present study was to evaluate the
      generation of VGE in a group of divers using a mixture of compressed oxygen,
      helium, and nitrogen (trimix) and to probe for their potential appearance in
      arterial circulation. Seven experienced male divers performed three dives in
      consecutive days according to trimix diving and decompression protocols generated
      by V-planner, a software program based on the Varying Permeability Model. The
      occurrence of VGE was monitored ultrasonographically for up to 90 min after
      surfacing, and the images were graded on a scale from 0 to 5. The performed
      diving activities resulted in a substantial amount of VGE detected in the right
      cardiac chambers and their frequent passage to the arterial side, in 9 of 21
      total dives (42%) and in 5 of 7 divers (71%). Concomitant measurement of mean
      pulmonary artery pressure revealed a nearly twofold augmentation, from 13.6 +/-
      2.8, 19.2 +/- 9.2, and 14.7 +/- 3.3 mmHg assessed before the first, second, and
      the third dive, respectively, to 26.1 +/- 5.4, 27.5 +/- 7.3, and 27.4 +/- 5.9
      mmHg detected after surfacing. No acute decompression-related disorders were
      identified. The observed high gas bubble loads and repeated microemboli in
      systemic circulation raise questions about the possibility of long-term adverse
      effects and warrant further investigation.

PMID- 20813976
TI  - Posttranslational modifications in histones underlie heat acclimation-mediated
      cytoprotective memory.
AB  - We have demonstrated that heat acclimation (AC) causes selective, long-lasting,
      transcriptional changes in cytoprotective and chromatin remodeling-associated
      genes, which maintain their AC transcriptome profile, despite the loss of the AC
      phenotype (Tetievsky et al. Physiol Genomics 34: 78-87, 2008). We postulated that
      AC memory involves upstream epigenetic information, which predisposes to rapid
      reacclimation (ReAC) and cytoprotective memory. Here we tested the hypothesis
      that posttranslational histone modifications are linked to this process. Rats
      subjected to AC (34 degrees C for 2 or 30 days), deacclimation (DeAC; 24 degrees
      C, 30 days), and ReAC (34 degrees C, 2 days), and untreated controls were used.
      Histone H4 lysine acetylation and histone H3 acetylation and phosphorylation in
      the heat shock element (HSE) of the promoters of heat shock protein-70 (hsp70)
      and -90 (hsp90) genes were examined. Histone acetyltransferase recruitment of
      TIP60 (60-kDa histone acetyltransferase-interactive protein), the catalytic
      subunit of NuH4, was used to validate acetylation. Heat shock factor-1 (HSF-1)
      HSE binding to the hsp70 and hsp90 genes was measured to confirm HSF-1 binding to
      euchromatin. Our results indicate that, while histone H3Ser10 phosphorylation
      occurred during the AC 2-day phase, AC constitutively elevated histone H4
      acetylation in the HSE of hsp70 and hsp90 promoters. HSF-1-HSE binding was
      detected in the hsp70 gene throughout AC-DeAC-ReAC. The hsp90 gene lacked HSF-1
      binding during DeAC, but resumed a high binding level upon ReAC. HSP-90 is a
      critical cytoprotective protein, and the HSF-1-hsp90 binding profile matched
      levels of this protein. We conclude that, while early histone H3 phosphorylation
      is probably required for subsequent histone H4 acetylation, the constitutively
      acetylated histone H4 and the preserved euchromatin state throughout AC-DeAC-ReAC
      predispose to rapid cytoprotective acclimatory memory.

PMID- 20813977
TI  - Optimizing heat dissipation for every environment: the cool ability of the skin
      to locally regulate sweating.

PMID- 20813978
TI  - Fluctuations and determinism of respiratory impedance in asthma and chronic
      obstructive pulmonary disease.
AB  - Asthma and COPD are chronic respiratory diseases that fluctuate widely with
      regard to clinical symptoms and airway obstruction, complicating treatment and
      prediction of exacerbations. Time series of respiratory impedance obtained by the
      forced oscillation technique are a convenient tool to study the respiratory
      system with high temporal resolution. In previous studies it was suggested that
      power-law-like fluctuations exist also in the healthy lung and that respiratory
      system impedance variability differs in asthma. In this study we elucidate such
      differences in a population of well-characterized subjects with asthma (n = 13,
      GINA 1+2), COPD (n = 12, GOLD I+II), and controls (n = 10) from time series at
      single frequency (12 min, f = 8 Hz). Maximum likelihood estimation did not rule
      out power-law behavior, accepting the null hypothesis in 17/35 cases (P > 0.05)
      and with significant differences in exponents for COPD (P < 0.03). Detrended
      fluctuation analysis exhibited scaling exponents close to 0.5, indicating few
      correlations, with no differences between groups (P > 0.14). In a second
      approach, we considered asthma and COPD as dynamic diseases, corresponding to
      changes of unknown parameters in a deterministic system. The similarity in shape
      between the combined probability distributions of normalized resistance and
      reactance was quantified by Wasserstein distances and reliably distinguished the
      two diseases (cross-validated predictive accuracy 0.80; sensitivity 0.83,
      specificity 0.77 for COPD). Wasserstein distances between 3+3 dimensional phase
      space reconstructions resulted in marginally better classification (accuracy
      0.84, sensitivity 0.83, specificity 0.85). These latter findings suggest that the
      dynamics of respiratory impedance contain valuable information for the diagnosis
      and monitoring of patients with asthma and COPD, whereas the value of the
      stochastic approach is not clear presently.

PMID- 20813979
TI  - Effect of graded hypoxia on supraspinal contributions to fatigue with unilateral
      knee-extensor contractions.
AB  - Supraspinal fatigue, defined as an exercise-induced decline in force caused by
      suboptimal output from the motor cortex, accounts for over one-quarter of the
      force loss after fatiguing contractions of the knee extensors in normoxia. We
      tested the hypothesis that the relative contribution of supraspinal fatigue would
      be elevated with increasing severities of acute hypoxia. On separate days, 11
      healthy men performed sets of intermittent, isometric, quadriceps contractions at
      60% maximal voluntary contraction to task failure in normoxia (inspired O(2)
      fraction/arterial O(2) saturation = 0.21/98%), mild hypoxia (0.16/93%), moderate
      hypoxia (0.13/85%), and severe hypoxia (0.10/74%). Electrical stimulation of the
      femoral nerve was performed to assess neuromuscular transmission and contractile
      properties of muscle fibers. Transcranial magnetic stimulation was delivered to
      the motor cortex to quantify corticospinal excitability and voluntary activation.
      After 10 min of breathing the test gas, neuromuscular function and cortical
      voluntary activation prefatigue were unaffected in any condition. The fatigue
      protocol resulted in ~ 30% declines in maximal voluntary contraction force in all
      conditions, despite differences in time-to-task failure (24.7 min in normoxia vs.
      15.9 min in severe hypoxia, P < 0.05). Potentiated quadriceps twitch force
      declined in all conditions, but the decline in severe hypoxia was less than that
      in normoxia (P < 0.05). Cortical voluntary activation also declined in all
      conditions, but the deficit in severe hypoxia exceeded that in normoxia (P <
      0.05). The additional central fatigue in severe hypoxia was not due to altered
      corticospinal excitability, as electromyographic responses to transcranial
      magnetic stimulation were unchanged. Results indicate that peripheral mechanisms
      of fatigue contribute relatively more to the reduction in force-generating
      capacity of the knee extensors following submaximal intermittent isometric
      contractions in normoxia and mild to moderate hypoxia, whereas supraspinal
      fatigue plays a greater role in severe hypoxia.

PMID- 20813981
TI  - Concomitant ventilatory and circulatory functions of the diaphragm and abdominal
      muscles.
AB  - Expulsive maneuvers (EMs) caused by simultaneous contraction of diaphragm and
      abdominal muscles shift substantial quantities of blood from the splanchnic
      circulation to the extremities. This suggests that the diaphragm assisted by
      abdominal muscles might accomplish ventilation and circulation simultaneously by
      repeated EMs. We tested this hypothesis in normal subjects by measuring changes
      (Delta) in body volume (Vb) by whole body plethysmography simultaneously with
      changes in trunk volume (Vtr) by optoelectronic plethysmography, which measures
      the same parameters as whole body plethysmography plus the volume of blood shifts
      (Vbs) between trunk and extremities: Vbs = DeltaVtr-DeltaVb. We also measured
      abdominal pressure, pleural pressure, the arterial pressure wave, and cardiac
      output (Qc). EMs with abdominal pressure ~100 cmH(2)O for 1 s, followed by 2-s
      relaxations, repeated over 90 s, produced a "stroke volume" from the splanchnic
      bed of 0.35 +/- 0.07 (SD) liter, an output of 6.84 +/- 0.75 l/min compared with a
      resting Qc of 5.59 +/- 1.14 l/min. Refilling during relaxation was complete, and
      the splanchnic bed did not progressively empty. Diastolic pressure increased by
      25 mmHg during each EM. Between EMs, Qc increased to 7.09 +/- 1.14 l/min due to
      increased stroke volume and heart rate. The circulatory function of the diaphragm
      assisted by simultaneous contractions of abdominal muscles with appropriate
      pressure and duration at 20 min(-1) can produce a circulatory output as great as
      resting Qc, as well as ventilation. These combined functions of the diaphragm
      have potential for cardiopulmonary resuscitation. The abdominal circulatory pump
      can act as an auxiliary heart.

PMID- 20813980
TI  - Tissue oxidative metabolism after extreme hemodilution with PEG-conjugated
      hemoglobin.
AB  - NADH-localized fluorometry was used as a noninvasive technique to monitor changes
      in the energy state of intact tissue (muscle and connective tissue), without
      anesthesia, as a function of blood plasma O(2)-carrying capacity in the hamster
      window chamber model. Acute moderate isovolemic hemodilution was induced by two
      isovolemic hemodilution steps: in the first step, 6% 70-kDa dextran (Dex70) was
      used to induce an acute anemic state (18% Hct); in the second step, exchange
      transfusion of polyethylene glycol (PEG) maleimide-conjugated Hb (4 g/dl, PEG-Hb)
      or Dex70 (6 g/dl) was used to reduce erythrocytes to 75% of baseline (11% Hct).
      PEG-Hb had six copies of PEG (5 kDa) conjugated to each human Hb (0.48 g PEG/g
      Hb) through extension arm-facilitated chemistry. Systemic parameters,
      microvascular perfusion, functional capillary density, intravascular and
      interstitial Po(2), and intracellular NADH fluorescence were monitored. Mean
      arterial blood pressure after extreme hemodilution was statistically
      significantly reduced for Dex70 compared with PEG-Hb. The presence of PEG-Hb in
      the circulation maintained positive acid-base balance. While microvascular blood
      flows were not different, functional capillary density was significantly higher
      for PEG-Hb than Dex70. Arteriolar Po(2) was higher in the presence of PEG-Hb than
      Dex70, but tissue and venular Po(2) were not different. Cellular energy
      metabolism (intracellular O(2)) in the tissues was improved with PEG-Hb. Moderate
      hemodilution to 18% Hct (6.4 g Hb/dl) brings tissue O(2) delivery to the verge of
      inadequacy. Extreme hemodilution to 11% Hct (3.7 g Hb/dl) produces tissue anoxia,
      and high-O(2)-affinity PEG-Hb (Po(2) at which blood is 50% saturated with O(2) =
      4 Torr, 1.1 g Hb/dl) only partially decreases anaerobic metabolism without
      increasing tissue Po(2).

PMID- 20813982
TI  - The complement component C5a is present in human coronary lesions in vivo and
      induces the expression of MMP-1 and MMP-9 in human macrophages in vitro.
AB  - The complement component C5a is formed during activation of the complement
      cascade and exerts chemotactic and proinflammatory effects. Macrophages, which
      are localized in the rupture-prone shoulder regions of coronary plaques, are
      thought to play a major role in plaque destabilization and rupture through the
      production of matrix metalloproteinases (MMPs). When human monocyte-derived
      macrophages were stimulated in vitro with C5a, MMP-1 and MMP-9 mRNA levels were
      significantly increased. Furthermore, C5a up-regulated MMP-1 and MMP-9 antigens
      and activity, as determined by ELISA and specific activity assays. These effects
      were blocked by antibodies against the receptor C5aR/CD88. In addition, blocking
      experiments revealed that MMP-1 expression was mediated by activation of the
      transcription factor AP-1, and MMP-9 expression was induced by activation of NF
      kappaB and AP-1. Immunohistochemical analysis of human coronary plaques
      demonstrated the colocalization of C5a, MMP-1, and MMP-9 in vivo. Together, these
      observations indicate that activation of the complement cascade and formation of
      C5a may play a role in the onset of acute coronary events by induction of MMPs in
      atherosclerotic lesions.

PMID- 20813983
TI  - Ligand field theory and the origin of life as an emergent feature of the periodic
      table of elements.
AB  - The assumption that all biological catalysts are either proteins or ribozymes
      leads to an outstanding enigma of biogenesis-how to determine the synthetic
      pathways to the monomers for the efficient formation of catalytic macromolecules
      in the absence of any such macromolecules. The last 60 years have witnessed
      chemists developing an understanding of organocatalysis and ligand field theory,
      both of which give demonstrable low-molecular-weight catalysts. We assume that
      transition-metal-ligand complexes are likely to have occurred in the deep ocean
      trenches by the combination of naturally occurring oceanic metals and ligands
      synthesized from the emergent CO(2), H(2), NH(3), H(2)S, and H(3)PO(4). We are
      now in a position to investigate experimentally the metal-ligand complexes, their
      catalytic function, and the reaction networks that could have played a role in
      the development of metabolism and life itself.

PMID- 20813984
TI  - New molluscan larval form: brooding and development in a hydrothermal vent
      gastropod, Ifremeria nautilei (Provannidae).
AB  - Despite extreme differences between some shallow and deep-sea habitats, the
      developmental modes and larval forms of deep-sea animals are typically similar to
      those of their shallow-water relatives. Here we report one of the first
      documented exceptions to this general rule. The hydrothermal vent snail Ifremeria
      nautilei displays two novel life-history traits: (1) an unusual uniformly
      ciliated larva that we here name Waren's larva, and (2) internal brood protection
      in a modified metapodial pedal gland. Waren's larva emerges from the internal
      brood pouch as a fully ciliated lecithotrophic larva with a unique external
      cuticle. The larvae swim with their posterior end forward and metamorphose into
      typical veliger larvae after 15 days at room temperature. Waren's larva is the
      only known example of a free-swimming pre-veliger larval stage in the higher
      gastropods and is the first new gastropod larval form to be described in more
      than 100 years.

PMID- 20813985
TI  - Morphological maturation level of the esophagus is associated with the number of
      circumesophageal muscle fibers during archenteron formation in the starfish
      Patiria (Asterina) pectinifera.
AB  - In echinoderms, the circumesophageal muscle is mesodermal in origin. Several
      studies of sea urchins have reported that the molecular events of myogenesis
      occur during the differentiation of the circumesophageal muscle in early
      embryogenesis. In contrast, few detailed reports have examined the
      differentiation of the circumesophageal muscle in larval starfish. Here, we
      examined the temporal-numeric distribution and differentiation of esophagus
      circular muscle fibers in the starfish Patiria pectinifera by using rhodamine
      phalloidin staining. Muscle fibers were not detected in mouth-forming larvae, but
      a mean of about 10 muscle fibers was observed in 48-h larvae, and about 26
      bundles were observed after 60 h. During the next 12 h, the number of muscle
      fiber bundles increased slightly to about 31 bundles and was stable until 96 h.

PMID- 20813986
TI  - Molecular phylogeny of the sacoglossa, with a discussion of gain and loss of
      kleptoplasty in the evolution of the group.
AB  - Sacoglossan sea slugs retain the chloroplasts from food algae in their cells
      (kleptoplasty) and obtain the photosynthetic products, but the capability of
      kleptoplasty differs among species. One evolutionary hypothesis for kleptoplasty
      is that the family Volvatellidae is the ancestral sacoglossan lineage in which
      kleptoplasty arose, but this is based on ambiguous phylogenetic relationships. To
      test this hypothesis, we analyzed sacoglossan phylogeny for concatenated
      sequences (approximately 4000 bp) of nuclear (18S rRNA) and mitochondrial (CO1,
      trnV, and 16S rRNA) genes of 18 sacoglossan species, using neighbor-joining,
      maximum parsimony, maximum likelihood, and Bayesian methods. The resultant
      phylogenetic trees clearly revealed monophyly of the order Sacoglossa (including
      the debatable genus Cylindrobulla), which contained two sister clades: the
      shelled sacoglossan group (Oxynoacea + Cylindrobulla) and the non-shelled group
      (Plakobranchacea). The family Volvatellidae was in a derived position within the
      Oxynoacea. The most parsimonious rearrangement of the character states of
      kleptoplasty on the phylogenetic tree suggested that (1) kleptoplasty was
      acquired at the basal position of the Sacoglossa (including Cylindrobulla) as non
      functional kleptoplasty, (2) functional kleptoplasty was gained in the
      Plakobranchacea clade, and (3) non-functional kleptoplasty was lost in the
      Volvatellidae lineage in the Oxynoacea clade.

PMID- 20813987
TI  - Effects of selfing on offspring survival and reproduction in a colonial
      simultaneous hermaphrodite (Bugula stolonifera, Bryozoa).
AB  - Understanding the consequences of selfing in simultaneous hermaphrodites requires
      investigating potential deleterious effects on fitness at all stages of life. In
      this study, I examined the effects of selfing throughout the life cycle of the
      marine bryozoan Bugula stolonifera, a colonial simultaneous hermaphrodite. In
      2008, larvae from field-collected colonies were cultured through metamorphosis to
      reproductively mature colonies either in the presence of one other colony, the
      paired treatment, or alone, the solitary treatment. Results demonstrated that
      selfing in this species is possible, in that colonies in the solitary treatment
      produced viable larvae that successfully completed metamorphosis. On average,
      however, these colonies released significantly fewer larvae, which experienced
      reduced rates of metamorphic initiation and completion compared to the paired
      treatment. These experiments were extended in 2009, when metamorphs from colonies
      reared in the solitary (n = 58) and paired (n = 61) treatments were transferred
      to the field for growth to reproductive maturity and then brought back to the
      laboratory for larval collection. Results revealed additional deleterious effects
      associated with selfing, as no viable larvae were recovered from colonies
      deriving from the solitary treatment. In contrast, offspring from the paired
      treatment released 1030 larvae and 99% initiated metamorphosis, 97% of which
      completed metamorphosis. Overall, selfed larvae not only had significantly
      decreased chances of survival, but those that did survive did not successfully
      reproduce.

PMID- 20813988
TI  - Abrupt change in food environment induces cloning in plutei of Dendraster
      excentricus.
AB  - Asexual reproduction, or cloning, of planktonic echinoderm larvae has been
      observed in the laboratory and in nature, but little is known about its ecology.
      Here we examine the effects of algal food density and of a change in food density
      on the incidence of cloning in larvae of the sand dollar Dendraster excentricus.
      Results indicate that a change in food concentration can induce cloning in
      plutei. Cultures transferred from a low to a high algal ration at the time when
      primary larvae were developing the third (posterodorsal) pair of larval arms
      showed decreased postoral arm length, unusual morphologies, and increased larval
      density in culture. These dense cultures of smaller plutei were produced within
      48 h of the food pulse. The result is consistent with the occurrence of a burst
      of cloning, possibly through anterior autotomization. A second feeding experiment
      demonstrated that anterior autotomization does occur in 4- to 6-arm plutei.
      Rather than constituting a developmental rarity, cloning may happen early and
      often in D. excentricus cohorts when environmental conditions favor rapid growth.

PMID- 20813989
TI  - Role of epicellular molecules in the selection of particles by the blue mussel,
      Mytilus edulis.
AB  - This study provides evidence that the suspension-feeding blue mussel, Mytilus
      edulis, uses biochemical cues to recognize its food. We identified lectins in
      mucus from the gills and labial palps, two pallial organs involved in the feeding
      process. These compounds were able to agglutinate rabbit and horse erythrocytes
      (RBC) and several species of marine microalgae representing different families.
      Additionally, the agglutination of RBC and microalgae was inhibited by several
      carbohydrates (fetuin, lipopolysaccharide (LPS), and mannose-related residues),
      suggesting that a suite of lectins may be present in mucus from the gills and
      labial palps. Results from feeding experiments, using microspheres with tailored
      surfaces, demonstrated that mussels preferentially ingested microspheres coated
      with the neoglycoproteins glucosamide-BSA and mannopyranosylphenyl-BSA but
      rejected in pseudofeces microspheres coated with BSA alone. The positive
      selection for neoglycoprotein-coated microspheres was inhibited when mussels were
      pre-incubated in seawater containing a solution of the same neoglycoprotein. Two
      surface properties of the microspheres, charge and wettability, had little effect
      on the observed selection process. Our results, along with our previous findings
      for oysters, suggest a new concept for the mechanism of particle selection in
      bivalves and perhaps other suspension-feeding organisms. Specifically, the
      selection of particles involves interactions between epiparticulate carbohydrates
      and lectins in the mucus produced by feeding organs.

PMID- 20813990
TI  - In vivo effects of brown tide on the feeding function of the gill of the northern
      quahog Mercenaria mercenaria (Bivalvia: Veneridae).
AB  - The in vivo response of adult northern quahogs, Mercenaria mercenaria, to
      Aureococcus anophagefferens (brown tide) at the level of the gill was determined
      using video-endoscopy. Feeding activity, particle-approach velocities, and
      ventral-groove-transport velocities were documented after the quahogs were
      exposed to Isochryis galbana (baseline observations) supplemented with either
      toxic or nontoxic A. anophagefferens at two bloom concentrations (8 x 10(5) or 2
      x 10(6) cells ml(-1)). Externally, there was no evidence of adverse effects of
      brown tide on feeding, as siphons remained extended and dilated. Toxic brown tide
      at both concentrations elicited gill muscular contractions, intermittent
      cessation of water flow, and decreased particle loading within the pallial
      cavity. The 8 x 10(5) cell ml(-1) toxic treatment had no significant effect on
      approach velocities or ventral-groove-transport velocities after 2 h, although
      time-averaging showed significant reduction of the latter during the last 30 min
      of exposure. The higher concentration of toxic brown tide caused a significant
      decrease in these velocities after only 1 h. Nontoxic brown tide produced none of
      these effects. Thus, A. anophagefferens compromised quahog feeding by stimulating
      contractions of the branchial musculature and interfering with lateral and
      ventral groove ciliary beating. These effects were both time- and concentration
      dependent and could be caused by either a dopaminergic or a serotonergic toxic
      factor.

PMID- 20813991
TI  - Photoresponses of the compound eye of the sandhopper Talitrus saltator
      (Crustacea, Amphipoda) in the ultraviolet-blue range.
AB  - The semi-terrestrial sandhopper Talitrus saltator uses celestial visual cues to
      orient along the sea-land axis of the beach. Previous spectral-filtering
      experiments suggested that it perceives directional information from wavelengths
      in the ultraviolet (UV)-blue range. Binary choice experiments between dark and UV
      (380-nm) light carried out on dark-adapted individuals of T. saltator showed
      photopositive movement to UV. Morphologically, each ommatidium in the eye
      consists of five retinula cells, four large and one small. In electroretinogram
      experiments, sensitivity of the dark-adapted eye is dominated by a receptor
      maximally sensitive at about 390-450 nm and secondarily sensitive at about 500
      550 nm. Selective light-adaptation experiments at 580 nm showed the apparent
      sensitivity decreasing at around the secondary sensitive range, thus disclosing
      the existence of UV-blue photoreceptor cells. Here the existence of UV-blue
      detection is confirmed, and evidence is provided that green and UV-blue visual
      pigments are located in the large and small retinula cells, respectively.

PMID- 20813992
TI  - Monocyte chemoattractant protein-1 released from alveolar macrophages mediates
      the systemic inflammation of acute alveolar hypoxia.
AB  - Alveolar hypoxia produces rapid systemic inflammation in rats. Several lines of
      evidence suggest that the inflammation is not initiated by low systemic tissue
      partial pressure of oxygen (Po(2)) but by a mediator released into the
      circulation by hypoxic alveolar macrophages. The mediator activates tissue mast
      cells to initiate inflammation. Monocyte chemoattractant protein-1/Chemokine (C-C
      motif) ligand 2 (MCP-1/CCL2) is rapidly released by hypoxic alveolar macrophages.
      This study investigated whether MCP-1 is the mediator of the systemic
      inflammation of alveolar hypoxia. Experiments in rats and in alveolar macrophages
      and peritoneal mast cells led to several results. (1) Alveolar hypoxia (10% O(2)
      breathing, 60 minutes) produced a rapid (5-minute) increase in plasma MCP-1
      concentrations in conscious intact rats but not in alveolar macrophage-depleted
      rats. (2) Degranulation occurred when mast cells were immersed in the plasma of
      hypoxic intact rats but not in the plasma of alveolar macrophage-depleted rats.
      (3) MCP-1 added to normoxic rat plasma and the supernatant of normoxic alveolar
      macrophages produced a concentration-dependent degranulation of immersed mast
      cells. (4) MCP-1 applied to the mesentery of normoxic intact rats replicated the
      inflammation of alveolar hypoxia. (5) The CCR2b receptor antagonist RS-102895
      prevented the mesenteric inflammation of alveolar hypoxia in intact rats.
      Additional data suggest that a cofactor constitutively generated in alveolar
      macrophages and present in normoxic body fluids is necessary for MCP-1 to
      activate mast cells at biologically relevant concentrations. We conclude that
      alveolar macrophage-borne MCP-1 is a key agent in the initiation of the systemic
      inflammation of alveolar hypoxia.

PMID- 20813993
TI  - Perivascular T-cell infiltration leads to sustained pulmonary artery remodeling
      after endothelial cell damage.
AB  - Pulmonary hypertension is a vascular proliferative disease characterized by
      pulmonary artery remodeling because of dysregulated endothelial and smooth muscle
      cell proliferation. Although the role of inflammation in the development of the
      disease is not well-defined, plexogenic lesions in human disease are
      characterized by perivascular inflammation composed, in part, of T cells. We
      explored the role of T-cell infiltration on pulmonary vascular remodeling after
      endothelial cell damage. We induced endothelial cell damage using monocrotaline
      and isolated the role of T cells by using Rag1(tm1Mom) mice and performing
      adoptive T-cell transfer. We found that monocrotaline causes pulmonary vascular
      endothelial cell injury followed by a perivascular inflammatory response. The
      infiltration of inflammatory cells primarily involves CD4(+) T cells and leads to
      the progressive muscularization of small (<30 MUm) arterioles. Pulmonary vascular
      proliferative changes were accompanied by progressive and persistent elevations
      in right ventricular pressure and right ventricular hypertrophy. Supporting the
      central role of CD4(+) T cells in the inflammatory response, Rag1(tm1Mom) (Rag1(
      /-)) mice, which are devoid of T and B cells, were protected from the development
      of vascular injury when exposed to monocrotaline. The introduction of T cells
      from control mice into Rag1(-/-) mice reproduced the vascular injury phenotype.
      These data indicate that after endothelial cell damage, CD4(+) T-cell
      infiltration participates in pulmonary vascular remodeling. This finding suggests
      that a CD4(+) T-cell immune response may contribute to the pathogenesis of
      inflammatory vascular lesions seen in some forms of pulmonary hypertension.

PMID- 20813994
TI  - Endovascular treatment or neurosurgical clipping of ruptured intracranial
      aneurysms: effect on angiographic vasospasm, delayed ischemic neurological
      deficit, cerebral infarction, and clinical outcome.
AB  - BACKGROUND AND PURPOSE: The effects of aneurysm treatment modality (clipping or
      coiling) on the incidence of cerebral vasospasm and infarction after subarachnoid
      hemorrhage have not been clearly defined. We hypothesized that there may be a
      difference in angiographic and clinical vasospasm, cerebral infarction, and
      clinical outcome between patients undergoing clipping compared to coiling.
      METHODS: A retrospective, exploratory analysis of 413 patients randomized into
      the CONSCIOUS-1 trial was conducted. Patients underwent baseline and follow-up
      catheter angiography and computed tomography, as well as clinical assessments.
      Radiology end points were adjudicated by central blinded review, and angiographic
      vasospasm was quantified by measurements of arterial diameters on catheter
      angiography. The effect of method of aneurysm treatment (clipping [n=199] or
      coiling [n=214]) on angiographic vasospasm, delayed ischemic neurological
      deficit, cerebral infarction, and clinical outcome was analyzed using univariate
      and multivariate logistic regression. Propensity matching was used to adjust for
      differences in baseline risk factors between clipped and coiled patients.
      RESULTS: In all patients and the propensity-matched subset, aneurysm coiling was
      associated with a significantly reduced risk of angiographic vasospasm and
      delayed ischemic neurological deficit compared to clipping. Cerebral infarction
      and clinical outcome were not associated with clipping or coiling. CONCLUSIONS:
      In this exploratory analysis, aneurysm coiling was associated with less
      angiographic vasospasm and delayed ischemic neurological deficit than surgical
      clipping, whereas no effect on cerebral infarction or clinical outcome was
      observed. Whether this is attributable to differences in baseline risk factors
      between clipped and coiled patients or a true difference cannot be proven here.

PMID- 20813995
TI  - Comprehensive overview of nursing and interdisciplinary rehabilitation care of
      the stroke patient: a scientific statement from the American Heart Association.

PMID- 20813996
TI  - Neuroprotective effect of isoflurane and N-methyl-D-aspartate receptors in
      ischemic brain injury.

PMID- 20813997
TI  - Striking rural-urban disparities observed in acute stroke care capacity and
      services in the pacific northwest: implications and recommendations.
AB  - BACKGROUND AND PURPOSE: The age-adjusted stroke death rate in adults aged >=45
      years is significantly higher in the Northwest region than in the rest of the
      United States. Alaska, Idaho, Montana, Oregon, and Washington have substantial
      rural and frontier areas with unique characteristics and complexities that pose
      challenges to timely acute stroke care and ultimately affect the patient.
      METHODS: A regional needs assessment was conducted to assess acute stroke care
      capacity and services in the Northwest region. Hospitals with an emergency
      department were surveyed with a standardized online tool based on the Brain
      Attack Coalition recommendations and developed by stroke neurologists, emergency
      medical services leaders, state public health professionals, and American Stroke
      Association members. RESULTS: Approximately 76% of hospitals completed the
      questionnaire. Striking rural-urban differences were seen with rural hospitals
      having a much lower capacity to adequately care for patients with stroke. Two
      thirds lacked the necessary personnel, one third lacked necessary neuroimaging
      equipment, and one fourth were functioning without written emergency department
      and tissue plasminogen activator stroke protocols. CONCLUSIONS: This survey
      represents the first comprehensive regional assessment of stroke care capacity
      and services both in the Northwest region and the whole United States. The
      findings have confirmed the need to focus on strengthening stroke personnel,
      increasing access to care, and promoting written protocols, especially in rural
      settings. Additionally, promoting stroke center certification, increasing the
      number of stroke registries throughout the region, encouraging use of inpatient
      stroke care protocols in rural hospitals, and conducting ongoing stroke care
      capacity and services surveys is highly recommended.

PMID- 20813998
TI  - Differential associations of cortical and subcortical cerebral atrophy with
      retinal vascular signs in patients with acute stroke.
AB  - BACKGROUND AND PURPOSE: The relationship of cortical and subcortical cerebral
      atrophy to cerebral microvascular disease is unclear. We aimed to assess the
      associations of retinal vascular signs with cortical and subcortical atrophy in
      patients with acute stroke. METHODS: In the Multi-Centre Retinal Stroke Study,
      1360 patients with acute stroke admitted to 2 Australian and 1 Singaporean
      tertiary hospital during 2005 to 2007 underwent neuroimaging and retinal
      photography. Cortical and subcortical cerebral atrophy were graded based on
      standard CT scans. A masked assessment of retinal photographs identified focal
      retinal vascular signs, including retinopathy and retinal arteriolar wall signs
      (ie, focal arteriolar narrowing, arteriovenous nicking, arteriolar wall light
      reflex) and measured quantitative signs (retinal arteriolar and venular caliber).
      RESULTS: After adjusting for age, gender, study site, hypertension,
      hypercholesterolemia, diabetes, and smoking status, none of the retinal vascular
      signs assessed were associated with cortical atrophy, whereas retinopathy (OR,
      1.9; CI, 1.2 to 3.0) and enhanced arteriolar light reflex (OR, 2.0; CI, 1.2 to
      3.2) were significantly associated with subcortical atrophy. CONCLUSIONS: Our
      finding that certain retinal vascular signs are associated with subcortical but
      not cortical atrophy, suggests a differential pathophysiology between these 2
      cerebral atrophy subtypes and a potential role for small vessel disease
      underlying subcortical cerebral atrophy.

PMID- 20813999
TI  - The spot sign is more common in the absence of multiple prior microbleeds.
AB  - BACKGROUND AND PURPOSE: Mural thickening and permeability changes in patients
      with amyloid angiopathy (CAA) and chronic hypertension are implicated in the
      pathophysiology of multiple, chronic subclinical microbleeds. The Spot sign,
      contrast extravasation on CT angiography, predicts hematoma expansion and is
      presumed to represent acute vessel damage. We hypothesize that the Spot sign is
      more common in patients without multiple prior chronic microbleeds. METHODS: A
      retrospective study was conducted of 59 patients presenting within 6 hours of
      primary intracranial hemorrhage onset undergoing CT angiography and MRI. CT
      angiography spot sign presence was documented blinded to MRI. Hematoma expansion
      was defined as >6 mL or 30% enlargement. The Boston criteria were applied to
      microbleed interpretation dichotomizing subjects into probable and negative CAA.
      Basal ganglia, thalamic, and brain stem microbleed location were interpreted as
      chronic hypertensive pattern. Univariate logistic regression and ordinal logistic
      regression analysis identified significant predictive factors between spot
      positive and -negative patients or microbleed pattern. RESULTS: The incidence of
      spot positivity was 42%, 22%, and 0% for CAA-negative, chronic hypertensive, and
      CAA-positive patients, respectively (P=0.01). CAA-negative patients had higher
      baseline National Institutes of Health Stroke Scale (P=0.039), larger follow-up
      hematoma volume (P=0.02), and poorer Rankin score (P=0.049) than chronic
      hypertensive or CAA-positive patients. After age adjustment, spot-positive
      (P=0.023), age-related white matter change (P=0.041), number of microbleeds
      (P<0.0001), and modified Rankin score (P=0.027) remained significantly different
      between groups. CONCLUSIONS: Boston criteria-defined CAA-negative status
      demonstrates the highest risk of spot positivity compared with patients with
      probable CAA and chronic hypertension.

PMID- 20814000
TI  - Strokes with minor symptoms: an exploratory analysis of the National Institute of
      Neurological Disorders and Stroke recombinant tissue plasminogen activator
      trials.
AB  - BACKGROUND AND PURPOSE: The pivotal National Institute of Neurological Disorders
      and Stroke recombinant tissue plasminogen activator trials excluded patients with
      ischemic stroke with specific minor presentations or rapidly improving symptoms.
      The recombinant tissue plasminogen activator product label notes that its use for
      minor neurological deficit or rapidly improving stroke symptoms has not been
      evaluated. As a result, patients with low National Institutes of Health Stroke
      Scale scores are not commonly treated in clinical practice. We sought to further
      characterize the patients with minor stroke who were included in the National
      Institute of Neurological Disorders and Stroke trials. METHODS: Minor strokes
      were defined as National Institutes of Health Stroke Scale score <= 5 at baseline
      for this retrospective analysis, because this subgroup is most commonly excluded
      from treatment in clinical practice and trials. Clinical stroke syndromes were
      defined based on prespecified National Institutes of Health Stroke Scale item
      score clusters. Clinical outcomes were reviewed generally and within these
      cluster subgroups. RESULTS: Only 58 cases had National Institutes of Health
      Stroke Scale scores of 0 to 5 in the National Institute of Neurological Disorders
      and Stroke trials (42 recombinant tissue plasminogen activator and 16 placebo),
      and 2971 patients were excluded from the trials due to "rapidly improving" or
      "minor symptoms" as the primary reason. No patients were enrolled with isolated
      motor symptoms, isolated facial droop, isolated ataxia, dysarthria, isolated
      sensory symptoms, or with only symptoms/signs not captured by the National
      Institutes of Health Stroke Scale score (ie, National Institutes of Health Stroke
      Scale=0). There were <= 3 patients with each of the other isolated deficits
      enrolled in the trial. CONCLUSIONS: The National Institute of Neurological
      Disorders and Stroke trials excluded a substantial number of strokes with minor
      presentations, those that were included were small in number, and conclusions
      about outcomes based on specific syndromes cannot be drawn. Further prospective,
      systematic study of this subgroup is needed.

PMID- 20814001
TI  - Validity of movement pattern kinematics as measures of arm motor impairment
      poststroke.
AB  - BACKGROUND AND PURPOSE: Upper limb motor impairment poststroke is commonly
      evaluated using clinical outcome measures such as the Fugl-Meyer Assessment.
      However, most clinical measures provide little information about motor patterns
      and compensations (eg, trunk displacement) used for task performance. Such
      information is obtained using movement quality kinematic variables (joint ranges,
      trunk displacement). Evaluation of movement quality may also help distinguish
      between levels of motor impairment severity in individuals poststroke. Our
      objective was to estimate concurrent and discriminant validity of movement
      quality kinematic variables for pointing and reach-to-grasp tasks. METHODS: A
      retrospective study of kinematic data (sagittal trunk displacement, shoulder
      flexion, shoulder horizontal adduction, elbow extension) and Fugl-Meyer
      Assessment scores from 86 subjects (subacute to chronic stroke) performing
      pointing and reaching tasks was done. Multiple and logistic regression analyses
      were used to estimate concurrent and discriminant validity respectively. Cutoff
      points for distinguishing between levels of upper limb motor impairment severity
      (mild, moderate to severe) were estimated using sensitivity/specificity decision
      plots. The criterion measure used was the Fugl-Meyer Assessment (upper limb
      section). RESULTS: The majority of variance in Fugl-Meyer Assessment scores was
      explained by a combination of trunk displacement and shoulder flexion (51%) for
      the pointing task and by trunk displacement alone (52%) for the reach-to-grasp
      task. Trunk displacement was the only variable that distinguished between levels
      of motor impairment severity. Cutoff points were 4.8 cm for pointing and 10.2 cm
      for reach-to-grasp movements. CONCLUSIONS: Movement quality kinematic variables
      are valid measures of arm motor impairment levels poststroke. Their use in
      regular clinical practice and research is justified.

PMID- 20814002
TI  - Common carotid intima-media thickness and framingham risk score predict incident
      carotid atherosclerotic plaque formation: longitudinal results from the study of
      health in Pomerania.
AB  - BACKGROUND AND PURPOSE: Cross-sectional studies describe a positive association
      between common carotid artery intima-media thickness (CCA-IMT) and carotid
      plaques (CP). However, longitudinal data on the predictive value of CCA-IMT for
      occurrence of CP are limited. Therefore, the role of increasing CCA-IMT in the
      atherosclerotic process is still discussed controversially. METHODS: We
      investigated the predictive value of CCA-IMT and the Framingham risk score (FRS)
      for incident CP formation in a population-based longitudinal study of 1922
      subjects aged 45 to 81 years who underwent ultrasonography of both carotid
      arteries and received vascular risk factor assessment at baseline and after 5
      years. CP was defined as any protruding focal thickening of the intima-media
      complex. Incident CP formation during follow-up was defined as the appearance of
      at least 1 CP in a previously plaque-free arterial segment (right and left
      common, internal, and external carotid arteries and carotid bifurcation).
      RESULTS: Among the 636 subjects without CP at baseline, 418 (66%) had at least 1
      incident CP during follow-up. In a multivariable negative binominal regression
      model adjusted for age, gender, and the FRS, the number of arterial segments
      affected by incident CP was 1.53-fold higher (CI, 1.12-2.07; P<0.01) for subjects
      in the highest quartile of the overall CCA-IMT distribution compared to those in
      the lowest quartile. CONCLUSIONS: Both CCA-IMT and FRS independently predict
      incident CP formation. The risk of CP formation may actually be underestimated in
      subjects with low FRS and high IMT.

PMID- 20814003
TI  - Receptor activity-modifying protein-1 augments cerebrovascular responses to
      calcitonin gene-related peptide and inhibits angiotensin II-induced vascular
      dysfunction.
AB  - BACKGROUND AND PURPOSE: Receptors for calcitonin gene-related peptide (CGRP) are
      composed of the calcitonin-like receptor in association with receptor activity
      modifying protein-1 (RAMP1). CGRP is an extremely potent vasodilator and may
      protect against vascular disease through other mechanisms. METHODS: We tested the
      hypothesis that overexpression of RAMP1 enhances vascular effects of CGRP using
      transgenic mice with ubiquitous expression of human RAMP1. Because angiotensin II
      (Ang II) is a key mediator of vascular disease, we also tested the hypothesis
      that RAMP1 protects against Ang II-induced vascular dysfunction. RESULTS:
      Responses to CGRP in carotid and basilar arteries in vitro as well as cerebral
      arterioles in vivo were selectively enhanced in human RAMP1 transgenic mice
      compared to littermate controls (P<0.05), and this effect was prevented by a CGRP
      receptor antagonist (P<0.05). Thus, vascular responses to CGRP are normally RAMP1
      limited. Responses of carotid arteries were examined in vitro after overnight
      incubation with vehicle or Ang II. In arteries from control mice, Ang II
      selectively impaired responses to the endothelium-dependent agonist acetylcholine
      by ~50% (P<0.05) via a superoxide-mediated mechanism. In contrast, Ang II did not
      impair responses to acetylcholine in human RAMP1 transgenic mice. CONCLUSIONS:
      RAMP1 overexpression increases CGRP-induced vasodilation and protects against Ang
      II-induced endothelial dysfunction. These findings suggest that RAMP1 may be a
      new therapeutic target to regulate CGRP-mediated effects during disease including
      pathophysiological states in which Ang II plays a major role.

PMID- 20814004
TI  - Generalizations about general anesthesia: the unsubstantiated condemnation of
      general anesthesia for patients undergoing intra-arterial therapy for anterior
      circulation stroke.

PMID- 20814006
TI  - Estimation of the onset time of cerebral ischemia using T1rho and T2 MRI in rats.
AB  - BACKGROUND AND PURPOSE: Time of ischemia onset is the most critical factor for
      patient selection for available drug treatment strategies. The purpose of this
      study was to evaluate the abilities of the absolute longitudinal rotating frame
      (T(1rho)) and transverse (T(2)) MR relaxation times to estimate the onset time of
      ischemia in rats. METHODS: Permanent middle cerebral artery occlusion in rats was
      used to induce focal cerebral ischemia and animals were imaged with
      multiparametric MRI at several time points up to 7 hours postischemia. Ischemic
      parenchyma was defined as tissue with apparent diffusion coefficient of water
      <70% from that in the contralateral nonischemic brain. RESULTS: The difference in
      the absolute T(1rho) and T(2) between ischemic and contralateral nonischemic
      striatum increased linearly within the first 6 hours of middle cerebral artery
      occlusion. The slopes for T(1rho) and T(2) fits for both tissue types were
      similar; however, the time offsets were significantly longer for both MR
      parameters in the cortex than in the striatum. CONCLUSIONS: T(1rho) and T(2) MRI
      provide estimates for the onset time of cerebral ischemia requiring regional
      calibration curves from ischemic brain. Assuming that patients with suspected
      ischemic stroke are scanned by MRI within this timeframe, these MRI techniques
      may constitute unbiased tools for stroke onset time evaluation potentially aiding
      the decision-making for drug treatment strategies.

PMID- 20814005
TI  - The EXCITE stroke trial: comparing early and delayed constraint-induced movement
      therapy.
AB  - BACKGROUND AND PURPOSE: Although constraint-induced movement therapy (CIMT) has
      been shown to improve upper extremity function in stroke survivors at both early
      and late stages after stroke, the comparison between participants within the same
      cohort but receiving the intervention at different time points has not been
      undertaken. Therefore, the purpose of this study was to compare functional
      improvements between stroke participants randomized to receive this intervention
      within 3 to 9 months (early group) to participants randomized on recruitment to
      receive the identical intervention 15 to 21 months after stroke (delayed group).
      METHODS: Two weeks of CIMT was delivered to participants immediately after
      randomization (early group) or 1 year later (delayed group). Evaluators blinded
      to group designation administered primary (Wolf Motor Function Test, Motor
      Activity Log) and secondary (Stroke Impact Scale) outcome measures among the 106
      early participants and 86 delayed participants before delivery of CIMT, 2 weeks
      thereafter, and 4, 8, and 12 months later. RESULTS: Although both groups showed
      significant improvements from pretreatment to 12 months after treatment, the
      earlier CIMT group showed greater improvement than the delayed CIMT group in Wolf
      Motor Function Test Performance Time and the Motor Activity Log (P<0.0001), as
      well as in Stroke Impact Scale Hand and Activities domains (P<0.0009 and 0.0214,
      respectively). Early and delayed group comparison of scores on these measures 24
      months after enrollment showed no statistically significant differences between
      groups. CONCLUSIONS: CIMT can be delivered to eligible patients 3 to 9 months or
      15 to 21 months after stroke. Both patient groups achieved approximately the same
      level of significant arm motor function 24 months after enrollment. Clinical
      Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT00057018.

PMID- 20814007
TI  - Histological features of symptomatic carotid plaques in relation to age and
      smoking: the oxford plaque study.
AB  - BACKGROUND AND PURPOSE: Rates of incident and recurrent cardiovascular events
      rise steadily with age, due partly to more extensive atherosclerotic burden.
      However, in patients with similarly severe symptomatic carotid stenosis,
      increasing age is associated with a greater risk of ipsilateral ischemic stroke.
      This effect may be due to age-related differences in the pathology of symptomatic
      carotid plaques. However, previous studies of plaque pathology in relation to age
      have not accounted for potential confounders, particularly smoking, which is
      often less prevalent in the elderly population undergoing endarterectomy. Method
      We related patient age (<55, 55 to 64, 65 to 74, 75+ years) and smoking habit
      (never, exsmoker, recent smoker, and current smoker; and number of cigarettes
      smoked per day) to detailed histological assessments of 526 carotid plaques from
      consecutive patients undergoing carotid endarterectomy for symptomatic carotid
      stenosis. RESULTS: Three hundred seventy-nine (72.1%) patients were male (mean/SD
      age 66.6/8.7). Current/recent smokers were on average 7 years younger at carotid
      endarterectomy than ex-/never smokers (P<0.001), and age at carotid
      endarterectomy decreased with increasing number of cigarettes smoked per day (P
      trend=0.005). Plaques from current/recent smokers had a lower prevalence of
      intraplaque hemorrhage (P -trend=0.01), but histology was otherwise similar to
      that in ex-/never smokers, and both groups showed similar changes with age. With
      increasing age, plaque calcification and large lipid core increased (P<0.001 and
      P=0.01, respectively) and fibrous tissue (P=0.01) decreased, but lymphocyte
      infiltration of the plaque (P=0.03) and cap (P=0.002) and overall plaque
      inflammation (P=0.03) also decreased such that overall plaque instability was
      unrelated to age. CONCLUSIONS: Smoking is associated with a lower age at carotid
      endarterectomy suggesting that it may accelerate the development and/or
      progression of atherosclerosis. However, the mechanisms of plaque instability
      seem largely unrelated to smoking. Plaques from younger patients had greater
      inflammatory cell infiltration, whereas those from older patients had a larger
      lipid core, but there were no age trends in overall plaque instability suggesting
      the increased risk of stroke in the elderly with symptomatic carotid stenosis is
      due to other factors.

PMID- 20814008
TI  - Impaired cerebral autoregulation in acute mountain sickness: incidental yet
      adaptive?

PMID- 20814009
TI  - Cellular microparticles as a marker for cerebral vasospasm in spontaneous
      subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Spontaneous subarachnoid hemorrhage (SAH) still has a
      high risk for poor outcome that is frequently attributable to symptomatic
      cerebral vasospasm (CVS). We hypothesize that cellular microparticles (MP) play a
      role in the pathogenesis of CVS and may serve as biomarkers for CVS. METHODS: In
      20 consecutive SAH patients, endothelial, leukocyte, platelet, and erythrocyte MP
      were measured during 15 days after ictus. CVS was detected by transcranial
      Doppler sonography. Twenty matched volunteers served as healthy controls.
      RESULTS: Endothelial, leukocyte, and erythrocyte MP were elevated in SAH patients
      compared to healthy controls. CD105(+) and CD62e(+) endothelial MP were
      significantly higher in SAH patients with Doppler sonographic CVS. CD105(+)
      endothelial MP were especially increased on the days of Doppler sonographic CVS
      onset. In patients experiencing cerebral infarction attributable to vasospasm,
      CD41(+) platelet MP were elevated in addition to endothelial MP. CD41(+) platelet
      MP were significantly higher in patients with any level of disability (modified
      Rankin Scale score >=1) compared to those who made a full recovery (modified
      Rankin Scale score=0) on discharge from hospital. CONCLUSIONS: Endothelial MP
      were elevated in patients with SAH. This elevation coincided with the occurrence
      of Doppler sonographic CVS and therefore could be a novel biomarker for CVS.
      Platelet MP might be involved in the pathogenesis of cerebral infarction
      attributable to vasospasm, resulting in neurological morbidity.

PMID- 20814010
TI  - Recovery of upper limb function after cerebellar stroke: lesion symptom mapping
      and arm kinematics.
AB  - BACKGROUND AND PURPOSE: Loss of movement coordination is the main postacute
      symptom after cerebellar infarction. Although the course of motor recovery has
      been described previously, detailed kinematic descriptions of acute stage ataxia
      are rare and no attempt has been made to link improvements in motor function to
      measures of neural recovery and lesion location. This study provides a
      comprehensive assessment of how lesion site and arm dysfunction are associated in
      the acute stage and outlines the course of upper limb motor recovery for the
      first 4 months after the infarction. METHODS: Sixteen adult patients with
      cerebellar stroke and 11 age-matched healthy controls participated. Kinematics of
      goal-directed and unconstrained finger-pointing movements were measured at the
      acute stage and in 2-week and 3-month follow-ups. MRI data were obtained for the
      acute and 3-month follow-up sessions. A voxel-based lesion map subtraction
      analysis was performed to examine the effect of ischemic lesion sites on
      kinematic performance. RESULTS: In the acute stage, nearly 70% of patients
      exhibited motor slowing with hand velocity and acceleration maxima below the
      range of the control group. MRI analysis revealed that in patients with impaired
      motor performance, lesions were more common in paravermal lobules IV/V and
      affected the deep cerebellar nuclei. Stroke affecting the superior cerebellar
      artery led to lower motor performance than infractions of the posterior
      cerebellar artery. By the 2-week-follow-up, hand kinematics had improved
      dramatically (gains in acceleration up to 86%). Improvements between the 2-week
      and the 3-month-follow-ups were less pronounced. CONCLUSIONS: In the acute stage,
      arm movements were mainly characterized by abnormal slowness (bradykinesia) and
      not dyscoordination (ataxia). The motor signs were associated with lesions in
      paravermal regions of lobules IV/V and the deep cerebellar nuclei. Motor recovery
      was fast, with the majority of gains in upper limb function occurring in the
      first 2 weeks after the acute phase.

PMID- 20814011
TI  - Prediction of major vascular events in patients with transient ischemic attack or
      ischemic stroke: a comparison of 7 models.
AB  - BACKGROUND AND PURPOSE: In patients with a recent TIA or minor stroke, prediction
      of long-term risk of major vascular events is important, but difficult. We aimed
      to study the external validity of currently available prediction models. METHODS:
      We validated predictions from 3 population-based models (Framingham, SCORE, and
      INDIANA project) and 4 stroke cohort-based models (Stroke Prognosis Instrument
      II, Oxford TIA, Dutch TIA study, and the ABCD(2) study) in an independent cohort
      of patients with a recent TIA or minor stroke. The validation cohort consisted of
      592 patients with TIA or minor stroke, with a mean follow-up of 2 years. The
      primary outcome was the 2-year risk of the composite outcome event of nonfatal
      stroke, myocardial infarction, or vascular death. We used calibration graphs and
      c-statistics to evaluate the 7 models. RESULTS: The 2-year risk of the primary
      outcome event was 12%. Calibration was adequate for stroke population-based
      studies. After adjustment for baseline risk and for prevalence of risk factors,
      calibration was adequate for the Dutch TIA, the ABCD(2), and Stroke Prognosis
      Instrument II models. Discrimination ranged from 0.61 to 0.68. CONCLUSIONS:
      Discrimination was poor for all currently available risk prediction models for
      patients with a recent TIA or minor stroke, indicating the need for stronger
      predictors. Clinical usefulness may be best for the ABCD(2) model, which had a
      limited number of easily obtainable variables, a reasonable c-statistic (0.64),
      and good calibration.

PMID- 20814012
TI  - Transient global amnesia and jugular vein incompetence.

PMID- 20814013
TI  - An oxidized extracellular oxidation-reduction state increases Nox1 expression and
      proliferation in vascular smooth muscle cells via epidermal growth factor
      receptor activation.
AB  - OBJECTIVE: To examine the effect of an oxidized extracellular oxidation-reduction
      (redox) state (E(h)) on the expression of NADPH oxidases in vascular cells.
      METHODS AND RESULTS: The generation of reactive oxygen species by NADPH oxidase
      (Nox)-based NADPH oxidases activates redox-dependent signaling pathways and
      contributes to the development of "oxidative stress" in vascular disease. An
      oxidized plasma redox state is associated with cardiovascular disease in humans;
      however, the cellular mechanisms by which the extracellular redox state may cause
      disease are not known. Aortic segments and cultured aortic smooth muscle cells
      were exposed to E(h) between -150 mV (reduced) and 0 mV (oxidized) by altering
      the concentration of cysteine and its disulfide, cystine, the predominant redox
      couple in plasma. A more oxidized E(h) increased the expression of Nox1 and
      resulted in Nox1-dependent proliferation of smooth muscle cells. Oxidized E(h)
      rapidly induced epidermal growth factor receptor phosphorylation via shedding of
      epidermal growth factor-like ligands from the plasma membrane and caused
      extracellular signal-regulated kinase 1/2-dependent phosphorylation of the
      transcription factors activating transcription factor-1 and cAMP-response element
      binding protein. Inhibition of epidermal growth factor receptor or extracellular
      signal-regulated kinase 1/2 activation, or addition of small interference RNA to
      activating transcription factor-1, prevented the increase in Nox1 expression.
      CONCLUSIONS: Our results identify a novel mechanism by which extracellular
      oxidative stress increases expression and activity of Nox1 NADPH oxidase and
      contributes to vascular disease.

PMID- 20814014
TI  - Coronary and aortic endothelial function affected by feedback between adiponectin
      and tumor necrosis factor alpha in type 2 diabetic mice.
AB  - OBJECTIVE: To verify that adiponectin and tumor necrosis factor (TNF)-alpha
      reciprocally regulate their expression, thereby synergistically affecting both
      coronary and aortic endothelial dysfunction in type 2 diabetic mice. METHODS AND
      RESULTS: We examined endothelium-dependent and endothelium-independent
      vasodilation/vasorelaxation of coronary arterioles and aortas in control mice,
      diabetic mice (Lepr(db)), and Lepr(db) treated with adiponectin or neutralizing
      antibody to TNF-alpha (anti-TNF-alpha). Endothelium-dependent vasodilation to
      acetylcholine in both coronary arterioles and aortas was blunted in Lepr(db)
      compared with control mice. Endothelium-independent vasodilation to sodium
      nitroprusside was comparable. Adiponectin and anti-TNF-alpha improved
      acetylcholine-induced vasodilation of coronary arterioles and aortas in Lepr(db)
      without affecting dilator response to sodium nitroprusside. Adiponectin protein
      expression was significantly reduced, and TNF-alpha protein expression was
      significantly greater, in coronary arterioles and aortas of Lepr(db) compared
      with control mice. Immunofluorescence staining results indicate that adiponectin
      was colocalized with endothelial cells. Anti-TNF-alpha treatment upregulated
      adiponectin protein expression in Lepr(db) coronary arterioles and aortas.
      Adiponectin administration reduced TNF-alpha protein expression in Lepr(db).
      Although adiponectin receptor 1 protein expression in coronary arterioles and
      aortas was similar between control and diabetic mice, adiponectin receptor 2
      protein expression was significantly reduced in Lepr(db). Both adiponectin and
      anti-TNF-alpha inhibited IkappaBalpha phosphorylation and nuclear factor kappaB
      protein expression in Lepr(db), suggesting that adiponectin and TNF-alpha
      signaling may converge on nuclear factor kappaB to reciprocally regulate their
      expression. CONCLUSIONS: A reciprocal suppression occurs between adiponectin and
      TNF-alpha that fundamentally affects the regulation of coronary and aortic
      endothelial function in type 2 diabetic mice.

PMID- 20814015
TI  - Cholesterol intake modulates plasma triglyceride levels in
      glycosylphosphatidylinositol HDL-binding protein 1-deficient mice.
AB  - OBJECTIVE: To determine whether plasma triglyceride levels in adult
      Glycosylphosphatidylinositol HDL-binding protein 1 (GPIHBP1)-deficient (Gpihbp1(
      /-)) mice would be sensitive to cholesterol intake. METHODS AND RESULTS: Gpihbp1(
      /-) mice were fed a Western diet containing 0.15% cholesterol. After 4 to 8
      weeks, their plasma triglyceride levels were 113 to 135 mmol/L. When 0.005%
      ezetimibe was added to the diet to block cholesterol absorption, Lpl expression
      in the liver was reduced significantly, and the plasma triglyceride levels were
      significantly higher (>170 mmol/L). We also assessed plasma triglyceride levels
      in Gpihbp1(-/-) mice fed Western diets containing either high (1.3%) or low
      (0.05%) amounts of cholesterol. The high-cholesterol diet significantly increased
      Lpl expression in the liver and lowered plasma triglyceride levels. CONCLUSIONS:
      Treatment of Gpihbp1(-/-) mice with ezetimibe lowers Lpl expression in the liver
      and increases plasma triglyceride levels. A high-cholesterol diet had the
      opposite effects. Thus, cholesterol intake modulates plasma triglyceride levels
      in Gpihbp1(-/-) mice.

PMID- 20814016
TI  - Selective reduction in the sphingomyelin content of atherogenic lipoproteins
      inhibits their retention in murine aortas and the subsequent development of
      atherosclerosis.
AB  - OBJECTIVE: We used the sphingomyelin (SM) synthase 2 (Sms2) gene knockout (KO)
      approach to test our hypothesis that selectively decreasing plasma lipoprotein SM
      can play an important role in preventing atherosclerosis. METHODS AND RESULTS:
      The sphingolipid de novo synthesis pathway is considered a promising target for
      pharmacological intervention in atherosclerosis. However, its potential is
      hampered because the substance's atherogenic mechanism is not completely
      understood. We prepared Sms2 and apolipoprotein E (Apoe) double-KO mice. They
      showed a significant decrease in plasma lipoprotein SM levels (35%, P<0.01) and a
      significant increase in ceramide and dihydroceramide levels (87.5% and 27%,
      respectively; P<0.01) but no significant changes in other tested sphingolipids,
      cholesterol, and triglyceride. Non-high-density lipoproteins from the double-KO
      mice showed a reduction of SM, but not cholesterol, and displayed less tendency
      toward aortic sphingomyelinase-mediated lipoprotein aggregation in vitro and
      retention in aortas in vivo when compared with controls. More important, at the
      age of 19 weeks, Sms2 KO/Apoe KO mice showed a significant reduction in
      atherosclerotic lesions of the aortic arch and root (52%, P<0.01) compared with
      controls. The Sms2 KO/Apoe KO brachiocephalic artery contained significantly less
      SM, ceramide, free cholesterol, and cholesteryl ester (35%, 32%, 58%, and 60%,
      respectively; P<0.01) than that of the Apoe KO brachiocephalic artery.
      CONCLUSIONS: Decreasing plasma SM levels through decreasing SMS2 activity could
      become a promising treatment for atherosclerosis.

PMID- 20814017
TI  - A disintegrin and metalloprotease 10 is a novel mediator of vascular endothelial
      growth factor-induced endothelial cell function in angiogenesis and is associated
      with atherosclerosis.
AB  - OBJECTIVE: To elucidate the downstream mechanisms of vascular endothelial growth
      factor receptor 2 (VEGFR2), a key receptor in angiogenesis, which has been
      associated with atherosclerotic plaque growth and instability. METHODS AND
      RESULTS: By using a yeast-2-hybrid assay, we identified A Disintegrin And
      Metalloprotease 10 (ADAM10) as a novel binding partner of VEGFR2. ADAM10 is a
      metalloprotease with sheddase activity involved in cell migration; however, its
      exact function in endothelial cells (ECs), angiogenesis, and atherosclerosis is
      largely unknown. For the first time to our knowledge, we show ADAM10 expression
      in human atherosclerotic lesions, associated with plaque progression and
      neovascularization. We demonstrate ADAM10 expression and activity in ECs to be
      induced by VEGF; also, ADAM10 mediates the ectodomain shedding of VEGFR2.
      Furthermore, VEGF induces ADAM10-mediated cleavage of vascular endothelium (VE)
      cadherin, which could increase vascular permeability and facilitate EC migration.
      Indeed, VEGF increases vascular permeability in an ADAM10- and ADAM17-dependent
      way; inhibition of ADAM10 reduces EC migration and chemotaxis. CONCLUSIONS: These
      data provide the first evidence of ADAM10 expression in atherosclerosis and
      neovascularization. ADAM10 plays a functional role in VEGF-induced EC function.
      These data open perspectives for novel therapeutic interventions in vascular
      diseases.

PMID- 20814018
TI  - Risk factor differences for aortic versus coronary calcified atherosclerosis: the
      multiethnic study of atherosclerosis.
AB  - OBJECTIVE: The goal of this study was to compare and contrast coronary artery
      calcium (CAC) with abdominal aortic calcium (AAC) in terms of their associations
      with traditional and novel cardiovascular disease (CVD) risk factors. METHODS AND
      RESULTS: We measured both AAC and CAC using computed tomography scans in 1974 men
      and women aged 45 to 84 years from a multiethnic cohort. Traditional and novel
      CVD risk factors were examined separately in relation to AAC and CAC, using
      logistic regression for qualitative categorical comparisons and multiple linear
      regression for quantitative continuous comparisons. AAC was significantly
      associated with cigarette smoking and dyslipidemia and showed no gender
      difference. In contrast, CAC showed much weaker associations with smoking and
      dyslipidemia and a strong male predominance. Age and hypertension were associated
      similarly and significantly with AAC and CAC. Novel risk factors generally showed
      no independent association with either calcium measure, although in subset
      analyses, phosphorus, but not calcium, was related to CAC. The receiver operating
      characteristic curves for the qualitative results and the r(2) values for the
      quantitative analyses were both much higher for AAC than for CAC. CONCLUSIONS:
      AAC showed stronger correlations with most CVD risk factors than did CAC. The
      predictive value of AAC compared with CAC for incident CVD events remains to be
      evaluated.

PMID- 20814019
TI  - Transcriptional upregulation of brain-derived neurotrophic factor in rostral
      ventrolateral medulla by angiotensin II: significance in superoxide homeostasis
      and neural regulation of arterial pressure.
AB  - RATIONALE: Oxidative stress in rostral ventrolateral medulla (RVLM), where
      sympathetic premotor neurons for the maintenance of neurogenic vasomotor tone are
      located, contributes to neural mechanisms of hypertension. Emerging evidence
      suggests that brain-derived neurotrophic factor (BDNF) manifests "nontrophic"
      actions. OBJECTIVE: We assessed the hypothesis that BDNF plays an active role in
      oxidative stress-associated neurogenic hypertension by maintaining superoxide
      anion (O-(.)2) homeostasis in RVLM. METHODS AND RESULTS: In Wistar-Kyoto rats,
      microinjection of angiotensin II (Ang II) bilaterally into RVLM upregulated BDNF
      mRNA and protein and induced cAMP response element binding protein (CREB)
      phosphorylation. The Ang II-induced BDNF upregulation in RVLM was attenuated by
      coadministration of the NADPH oxidase inhibitor apocynin; the superoxide
      dismutase mimetic tempol; or an antisense oligonucleotide against CREB.
      Intracisternal infusion of Ang II elicited phosphorylation of p47(phox) subunit
      of NADPH oxidase, suppression of mitochondrial electron coupling capacity, and
      augmentation in mitochondrial uncoupling protein (UCP)2 expression in RVLM. The
      former 2 cellular events were enhanced, whereas UCP2 upregulation was attenuated
      by gene knockdown of BDNF or depletion of tropomyosin receptor kinase (Trk)B
      ligands with recombinant human TrkB-Fc fusion protein. The same treatments also
      significantly potentiated both Ang II-induced (O-(.)2) production in RVLM and
      chronic pressor response. CONCLUSIONS: Ang II induces (O-(.)2) -dependent
      upregulation of BDNF in RVLM via phosphorylation of CREB. The Ang II-activated
      BDNF/TrkB signaling, in turn, exerts negative-feedback regulation on tissue (O
      (.)2) level in RVLM through inhibition of p47(phox) phosphorylation, preservation
      of mitochondrial electron transport capacity, and upregulation of mitochondrial
      UCP2, resulting in protection against Ang II-induced oxidative stress and long
      term pressor response.

PMID- 20814020
TI  - Differential regulation of proteasome function in isoproterenol-induced cardiac
      hypertrophy.
AB  - RATIONALE: Proteasomal degradation is altered in many disease phenotypes
      including cardiac hypertrophy, a prevalent condition leading to heart failure.
      Our recent investigations identified heterogeneous subpopulations of proteasome
      complexes in the heart and implicated multiple mechanisms for their regulation.
      OBJECTIVE: The study aimed at identification of molecular mechanisms changing
      proteasome function in the hypertrophic heart. METHOD AND RESULTS: Proteasome
      function, expression, and assembly were analyzed during the development of
      cardiac hypertrophy induced by beta-adrenergic stimulation. The analysis
      revealed, for the first time, divergent regulation of proteasome function in
      cardiac hypertrophy. Proteasome complexes have 3 different proteolytic
      activities, which are ATP-dependent for 26S complexes (19S assembled with 20S)
      and ATP-independent for 20S core particles. The 26S activities were enhanced in
      hypertrophic hearts, partially because of increased expression and assembly of
      19S subunits with 20S core complexes. In contrast, caspase- and trypsin-like 20S
      activities were significantly decreased. Activation of endogenous cAMP-dependent
      protein kinase (PKA) rescued the depressed 20S functions, supporting the notion
      that PKA signaling is a positive regulator of protein degradation in the heart.
      Chymotrypsin-like 20S activity was stably maintained during cardiac remodeling,
      indicating a switch in proteasome subpopulations, which was supported by altered
      expression and incorporation of inducible beta subunits. CONCLUSIONS: Three novel
      mechanisms for the regulation of proteasome activities were discovered in the
      development of cardiac hypertrophy: (1) increased incorporation of inducible
      subunits in 20S proteasomes; (2) enhanced 20S sensitivity to PKA activation; and
      (3) increased 26S assembly. PKA modulation of proteasome complexes may provide a
      novel therapeutic avenue for restoration of cardiac function in the diseased
      myocardium.

PMID- 20814021
TI  - Interleukin-17-dependent autoimmunity to collagen type V in atherosclerosis.
AB  - RATIONALE: Considerable evidence shows atherosclerosis to be a chronic
      inflammatory disease in which immunity to self-antigens contributes to disease
      progression. We recently identified the collagen type V [col(V)] alpha1(V) chain
      as a key autoantigen driving the Th17-dependent cellular immunity underlying
      another chronic inflammatory disease, obliterative bronchiolitis. Because
      specific induction of alpha1(V) chains has previously been reported in human
      atheromas, we postulated involvement of col(V) autoimmunity in atherosclerosis.
      OBJECTIVE: To determine whether col(V) autoimmunity may be involved in the
      pathogenesis of atherosclerosis. METHODS AND RESULTS: Here, we demonstrate Th17
      dependent anti-col(V) immunity to be characteristic of atherosclerosis in human
      coronary artery disease (CAD) patients and in apolipoprotein E-null (ApoE(-/-))
      atherosclerotic mice. Responses were alpha1(V)-specific in CAD with variable Th1
      pathway involvement. In early atherosclerosis in ApoE(-/-) mice, anti-col(V)
      immunity was tempered by an interleukin (IL)-10-dependent mechanism. In support
      of a causal role for col(V) autoimmunity in the pathogenesis of atherosclerosis,
      col(V) sensitization of ApoE(-/-) mice on a regular chow diet overcame IL-10
      mediated inhibition of col(V) autoimmunity, leading to increased atherosclerotic
      burden in these mice and local accumulation of IL-17-producing cells,
      particularly in the col(V)-rich adventitia subjacent to the atheromas.
      CONCLUSIONS: These findings establish col(V) as an autoantigen in human CAD and
      show col(V) autoimmunity to be a consistent feature in atherosclerosis in humans
      and mice. Furthermore, data are consistent with a causative role for col(V) in
      the pathogenesis of atherosclerosis.

PMID- 20814022
TI  - Level of G protein-coupled receptor kinase-2 determines myocardial
      ischemia/reperfusion injury via pro- and anti-apoptotic mechanisms.
AB  - RATIONALE: Activation of prosurvival kinases and subsequent nitric oxide (NO)
      production by certain G protein-coupled receptors (GPCRs) protects myocardium in
      ischemia/reperfusion injury (I/R) models. GPCR signaling pathways are regulated
      by GPCR kinases (GRKs), and GRK2 has been shown to be a critical molecule in
      normal and pathological cardiac function. OBJECTIVE: A loss of cardiac GRK2
      activity is known to arrest progression of heart failure (HF), at least in part
      by normalization of cardiac beta-adrenergic receptor (betaAR) signaling. Chronic
      HF studies have been performed with GRK2 knockout mice, as well as expression of
      the betaARKct, a peptide inhibitor of GRK2 activity. This study was conducted to
      examine the role of GRK2 and its activity during acute myocardial ischemic injury
      using an I/R model. METHODS AND RESULTS: We demonstrate, using cardiac-specific
      GRK2 and betaARKct-expressing transgenic mice, a deleterious effect of GRK2 on in
      vivo myocardial I/R injury with betaARKct imparting cardioprotection. Post-I/R
      infarct size was greater in GRK2-overexpressing mice (45.0+/-2.8% versus 31.3+/
      2.3% in controls) and significantly smaller in betaARKct mice (16.8+/-1.3%,
      P<0.05). Importantly, in vivo apoptosis was found to be consistent with these
      reciprocal effects on post-I/R myocardial injury when levels of GRK2 activity
      were altered. Moreover, these results were reflected by higher Akt activation and
      induction of NO production via betaARKct, and these antiapoptotic/survival
      effects could be recapitulated in vitro. Interestingly, selective antagonism of
      beta(2)ARs abolished betaARKct-mediated cardioprotection, suggesting that
      enhanced GRK2 activity on this GPCR is deleterious to cardiac myocyte survival.
      CONCLUSION: The novel effect of reducing acute ischemic myocardial injury via
      increased Akt activity and NO production adds significantly to the therapeutic
      potential of GRK2 inhibition with the betaARKct not only in chronic HF but also
      potentially in acute ischemic injury conditions.

PMID- 20814023
TI  - Inhibition of elevated Ca2+/calmodulin-dependent protein kinase II improves
      contractility in human failing myocardium.
AB  - RATIONALE: Heart failure (HF) is known to be associated with increased
      Ca(2+)/calmodulin-dependent protein kinase (CaMK)II expression and activity.
      There is still controversial discussion about the functional role of CaMKII in
      HF. Moreover, CaMKII inhibition has never been investigated in human myocardium.
      OBJECTIVE: We sought to investigate detailed CaMKIIdelta expression in end-stage
      failing human hearts (dilated and ischemic cardiomyopathy) and the functional
      effects of CaMKII inhibition on contractility. METHODS AND RESULTS: Expression
      analysis revealed that CaMKIIdelta, both cytosolic delta(C) and nuclear delta(B)
      splice variants, were significantly increased in both right and left ventricles
      from patients with dilated or ischemic cardiomyopathy versus nonfailing.
      Experiments with isometrically twitching trabeculae revealed significantly
      improved force frequency relationships in the presence of CaMKII inhibitors (KN
      93 and AIP). Increased postrest twitches after CaMKII inhibition indicated an
      improved sarcoplasmic reticulum (SR) Ca(2+) loading. This was confirmed in
      isolated myocytes by a reduced SR Ca(2+) spark frequency and hence SR Ca(2+)
      leak, resulting in increased SR Ca(2+) load when inhibiting CaMKII. Ryanodine
      receptor type 2 phosphorylation at Ser2815, which is known to be phosphorylated
      by CaMKII thereby contributing to SR Ca(2+) leak, was found to be markedly
      reduced in KN-93-treated trabeculae. Interestingly, CaMKII inhibition did not
      influence contractility in nonfailing sheep trabeculae. CONCLUSIONS: The present
      study shows for the first time that CaMKII inhibition acutely improves
      contractility in human HF where CaMKIIdelta expression is increased. The
      mechanism proposed consists of a reduced SR Ca(2+) leak and consequently
      increased SR Ca(2+) load. Thus, CaMKII inhibition appears to be a possible
      therapeutic option for patients with HF and merits further investigation.

PMID- 20814025
TI  - Thanks be to zebrafish.

PMID- 20814026
TI  - Circulating microRNAs as potential biomarkers of coronary artery disease: a
      promise to be fulfilled?

PMID- 20814027
TI  - Making muscle: overview to "Cardiovascular lineage commitment during development
      and regeneration" series.

PMID- 20814028
TI  - Endoplasmic reticulum stress and inflammation in obesity and diabetes.
AB  - Obesity is a major problem worldwide that increases risk for a wide range of
      diseases, including diabetes and heart disease. As such, it is increasingly
      important to understand how excess adiposity can perturb normal metabolic
      functions. It is now clear that this disruption involves not only pathways
      controlling lipid and glucose homeostasis but also integration of metabolic and
      immune response pathways. Under conditions of nutritional excess, this
      integration can result in a metabolically driven, low-grade, chronic inflammatory
      state, referred to as "metaflammation," that targets metabolically critical
      organs and tissues to adversely affect systemic homeostasis. Endoplasmic
      reticulum dysfunction is another important feature of chronic metabolic disease
      that is also linked to both metabolic and immune regulation. A thorough
      understanding of how these pathways intersect to maintain metabolic homeostasis,
      as well as how this integration is altered under conditions of nutrient excess,
      is important to fully understand, and subsequently treat, chronic metabolic
      diseases.

PMID- 20814029
TI  - Plasticity and heterogeneity in the generation of memory B cells and long-lived
      plasma cells: the influence of germinal center interactions and dynamics.
AB  - In the humoral response, short-lived plasmablasts generate an early burst of Ab
      that probably plays an initial protective role. Simultaneously, another arm of
      the response is often triggered that leads to delayed effector function but long
      term protection. This arm comprises the germinal center response and its
      products: long-lived memory B (B(mem)) cells and plasma cells (PCs). The factors
      that control the differentiation of PCs and B(mem) cells, as well as the
      composition and function of the memory compartment--how it self-renews while
      generating rapid secondary effector function--are poorly understood. Recent work
      in mice and humans is beginning to illuminate these issues. We review this
      progress, with emphasis on events in the germinal center, especially B-T
      interactions, which influence the development of memory and PC compartments and
      on B(mem) cell heterogeneity that may underlie flexibility and self-renewal of
      long-lived humoral immunity.

PMID- 20814030
TI  - Domain structure of virulence-associated response regulator PhoP of Mycobacterium
      tuberculosis: role of the linker region in regulator-promoter interaction(s).
AB  - The PhoP and PhoR proteins from Mycobacterium tuberculosis form a highly specific
      two-component system that controls expression of genes involved in complex lipid
      biosynthesis and regulation of unknown virulence determinants. The several
      functions of PhoP are apportioned between a C-terminal effector domain (PhoPC)
      and an N-terminal receiver domain (PhoPN), phosphorylation of which regulates
      activation of the effector domain. Here we show that PhoPN, on its own,
      demonstrates PhoR-dependent phosphorylation. PhoPC, the truncated variant bearing
      the DNA binding domain, binds in vitro to the target site with affinity similar
      to that of the full-length protein. To complement the finding that residues
      spanning Met(1) to Arg(138) of PhoP constitute the minimal functional PhoPN, we
      identified Arg(150) as the first residue of the distal PhoPC domain capable of
      DNA binding on its own, thereby identifying an interdomain linker. However,
      coupling of two functional domains together in a single polypeptide chain is
      essential for phosphorylation-coupled DNA binding by PhoP. We discuss
      consequences of tethering of two domains on DNA binding and demonstrate that
      linker length and not individual residues of the newly identified linker plays a
      critical role in regulating interdomain interactions. Together, these results
      have implications for the molecular mechanism of transmission of conformation
      change associated with phosphorylation of PhoP that results in the altered DNA
      recognition by the C-terminal domain.

PMID- 20814031
TI  - Adolescent biological maturity and physical activity: biology meets behavior.
AB  - The decline in physical activity (PA) across adolescence is well established but
      influence of biological maturity on the process has been largely overlooked. This
      paper reviews the limited number of studies which examine the relationship
      between timing of biological maturity and PA. Results are generally inconsistent
      among studies. Other health-related behaviors are also considered in an effort to
      highlight the complexity of relationships between biological maturation and
      behavior and to provide future research directions.

PMID- 20814032
TI  - Insights into developmental muscle metabolism through the use of 31P-magnetic
      resonance spectroscopy: a review.
AB  - (31)phosphorous-magnetic resonance spectroscopy ((31)P-MRS) has become an
      extremely valuable technique to investigate changes in muscle metabolism
      noninvasively and in vivo. The purpose of this article is to critically review
      how (31)P-MRS has contributed to current understanding of muscle metabolic
      function in healthy children and adolescents. In addition, an overview of the
      basic principles of (31)P-MRS and its application to the study of muscle
      metabolism is provided and discussed in relation to child-specific methodological
      concerns when using this technique.

PMID- 20814033
TI  - Maternal prepregnancy overweight and offspring fatness and blood pressure: role
      of physical activity.
AB  - The purpose of this study was to examine if offspring physical activity may
      affect the relationship between maternal overweight and offspring fatness and
      blood pressure (BP). Subjects included 144 maternal-child pairs (n = 74 boys and
      70 girls, mean age = 7.3 yrs). Maternal prepregnancy BMI was determined by self
      report. Offspring characteristics included resting systolic and diastolic BP,
      body fatness by dual energy x-ray absorbtiometry, and moderate-to-vigorous
      physical activity (MVPA) using the Actigraph accelerometer. Children whose
      mothers were overweight or obese prepregnancy (Prepreg OW) were significantly
      larger and fatter than children from mothers with a normal prepregnancy BMI
      (Prepreg NORM). Prepreg OW children also had higher mean arterial pressure than
      Prepreg NORM children. BP values were not different across maternal Prepreg BMI/
      MVPA groups. Percent fat was significantly different across Prepreg BMI/MVPA
      groups. Prepreg OW children that did not meet the daily recommended value of MVPA
      were the fattest. Prepreg OW children that attained (3)60 min of MVPA/ day had a
      mean percent body fat that was similar to Prepreg NORM children of either MVPA
      group.

PMID- 20814034
TI  - Modeling the links between young swimmers' performance: energetic and biomechanic
      profiles.
AB  - The aim was to develop a path-flow analysis model for young swimmers' performance
      based on biomechanical and energetic parameters, using structural equation
      modeling. Thirty-eight male young swimmers served as subjects. Performance was
      assessed by the 200-m freestyle event. For biomechanical assessment the stroke
      length, the stroke frequency and the swimming velocity were analyzed. Energetics
      assessment included the critical velocity, the stroke index and the propulsive
      efficiency. The confirmatory model explained 79% of swimming performance after
      deleting the stroke index-performance path, which was nonsignificant (SRMR =
      0.06). As a conclusion, the model is appropriate to explain performance in young
      swimmers.

PMID- 20814035
TI  - Describing patterns of physical activity in adolescents using global positioning
      systems and accelerometry.
AB  - This study aimed to describe the location and intensity of free-living physical
      activity in New Zealand adolescents during weekdays and weekend days using Global
      Positioning Systems (GPS), accelerometry, and Geographical Information Systems
      (GIS). Participants (n = 79) aged 12-17 years (M = 14.5, SD 1.6) recruited from
      two large metropolitan high schools each wore a GPS watch and an accelerometer
      for four consecutive days. GPS and accelerometer data were integrated with GIS
      software to map the main locations of each participant's episodes of moderate
      vigorous physical activity. On average participants performed 74 (SD 36) minutes
      of moderate and 7.5 (SD 8) minutes of vigorous activity per day, which on
      weekdays was most likely to occur within a 1 km radius of their school or 150
      meters of their home environment. On weekends physical activity patterns were
      more disparate and took place outside of the home environment. Example maps were
      generated to display the location of moderate to vigorous activity for weekdays
      and weekends.

PMID- 20814036
TI  - A validation study of assessing physical activity and sedentary behavior in
      children aged 3 to 5 years.
AB  - Assessing young children's physical activity and sedentary behavior can be
      challenging and costly. This study aimed to assess the validity of a brief survey
      about activity preferences as a proxy of physical activity and of a 7-day
      activity diary, both completed by the parents and using accelerometers as a
      reference measure. Thirty-four parents and their children (aged 3-5 years) who
      attended childcare centers in Sydney (Australia) were recruited for the study.
      Parents were asked to complete a 9-item brief survey about activity preferences
      of their child and a 7-day diary recording the child's physical activity and
      sedentary behaviors. Both measures were compared with accelerometer data
      collected from the child over the same period as the diary survey. The findings
      suggest that parent completed diaries have acceptable correlation coefficients
      with accelerometer measures and could be considered in future research assessing
      physical activity and sedentary behavior of children aged 3-5 years.

PMID- 20814037
TI  - Bone speed of sound, bone turnover and IGF-I in adolescent synchronized swimmers.
AB  - This pilot study compared bone speed of sound (SOS), bone turnover and insulin
      like growth factor 1 (IGF-1) between 20 Caucasian, postmenarcheal, adolescent
      synchronized swimmers (SS) and 20 aged- and maturity-matched nonswimmers (NS).
      Daily dietary intake and physical activity levels were also assessed. Bone SOS
      was measured by quantitative ultrasound. Blood samples were analyzed for
      osteocalcin, cross-linked N-teleopeptide of type I collagen (NTx), IGF-I and 25
      OH vitamin D. Although no differences in bone SOS or turnover markers were
      observed between groups, the lower IGF-1 and vitamin D intake found in
      synchronized swimmers, in combination with their higher strenuous activity
      levels, should be further explored.

PMID- 20814038
TI  - Oxygen uptake efficiency slope in healthy children.
AB  - The objective of this study was to investigate the characteristics of the
      submaximal Oxygen Uptake Efficiency Slope (OUES) in a healthy pediatric
      population. Bicycle ergometry exercise tests with gas-analyses were performed in
      46 healthy children aged 7-17 years. Maximal OUES, submaximal OUES, VO(2)peak,
      V(E)peak, and ventilatory threshold (VT) were determined. The submaximal OUES
      correlated highly with VO(2)peak, V(E)peak, and VT. Strong correlations were
      found with basic anthropometric variables. The submaximal OUES could provide an
      objective, independent measure of cardiorespiratory function in children,
      reflecting efficiency of ventilation. We recommend expressing OUES values
      relative to Body Surface Area (BSA) or Fat Free Mass (FFM).

PMID- 20814039
TI  - Confounding effect of biologic maturation on sex differences in physical activity
      and sedentary behavior in adolescents.
AB  - Sex differences in physical activity (PA) through pubertal maturation and the
      growth spurt are often attributed to changing interests. The contribution of sex
      differences in biological maturation to the adolescent decline has received
      limited attention. This study examined the contribution of somatic maturation to
      sex differences in objective assessments of sedentary behavior and PA in
      Portuguese adolescents (N = 302, aged 13-16 years). Maturation was estimated from
      the percentage of predicted mature stature and physically active and inactive
      behaviors assessed with Actigraph GT1M accelerometers. The influence of age, sex
      and their interaction on body size, maturation and physical behaviors were
      examined using factorial ANOVA and, subsequently, ANCOVA (controlling for
      maturation) tested the effect of sex. Males spent more time in MVPA and less time
      in sedentary behavior than females. However, sex differences were attenuated when
      maturation was controlled; thus suggesting that maturity may play an important
      role in adolescent behaviors.

PMID- 20814040
TI  - Assessment of child-specific aerobic fitness and anaerobic capacity by the use of
      the power-time relationships constants.
AB  - This study first aimed to compare critical power (CP) and anaerobic work capacity
      (AWC), to laboratory standard evaluation methods such as maximal oxygen uptake
      (VO(2)max) and maximal accumulated oxygen deficit (MAOD). Secondly, this study
      compared child and adult CP and AWC values. Subjects performed a maximal graded
      test to determine VO(2)max and maximal aerobic power (MAP); and four constant
      load exercises. In children, CP (W * kg(-1)) was related to VO(2)max (ml * kg(-1)
      * min(-1); r = .68; p = .004). AWC (J * kg(-1) in children was related to MAOD (r
      = .58; p = .018). Children presented lower AWC (J * kg(-1); p = .001) than
      adults, but similar CP (%MAP) values. CP (%MAP and W * kg(-1) and AWC (J * kg(-1)
      were significantly related to laboratory standard evaluation methods but low
      correlation indicated that they cannot be used interchangeably. CP (%MAP) was
      similar in children and adults, but AWC (J * kg(-1) was significantly lower in
      children. These conclusions support existing knowledge related to child-adults
      characteristics.

PMID- 20814041
TI  - Linking young people's knowledge of public health guidelines to physical activity
      levels in England.
AB  - Using the 2007 Health Survey for England, we examine whether knowledge of
      guidelines is linked to physical activity levels for 1,954 children aged 11-15,
      and the correlates of adhering to the guidelines. For girls, knowing the
      guidelines was associated with meeting them, but was weak among boys, for whom
      only white ethnicity was associated with meeting the guidelines. For girls, being
      younger, white, and from a manual social class background was associated with
      meeting the guidelines. Findings support the call for physical activity-promoting
      policy and programs aimed at specific groups of children who are prone to lower
      levels of activity.

PMID- 20814042
TI  - Physical training of 9- to 10-year-old children with obesity to lactate threshold
      intensity.
AB  - The purpose of this study was to apply the lactate threshold concept to develop a
      more evidence-informed exercise program for obese children. 60 obese children (26
      girls and 34 boys, age: 9-10 years, BMI: 25.4 +/- 2.2kg/m(2)) were recruited and
      half of them were randomly selected to be trained for eight weeks with a
      controlled exercise intensity at lactate threshold. The trained children achieved
      significant improvements on their body composition and functional capacity
      compared with the control group. The findings suggested that the training program
      with intensity at lactate threshold is effective and safe for 9-10 year old
      children with obesity.

PMID- 20814043
TI  - Low rate of conversion to transfemoral approach when attempting both radial
      arteries for coronary angiography and percutaneous coronary intervention: a study
      of 1,826 consecutive procedures.
AB  - AIMS: Despite a proven safety profile, the transradial approach (TRA) for
      coronary procedures is regarded by many as complicated and the second-choice
      arterial access, with a high conversion rate to transfemoral access (TFA). This
      study reports causes of failure and the contemporary success rate of TRA when
      both radial arteries are attempted first before converting to TFA. METHODS: This
      prospective, single-center study included 1,826 consecutive patients referred for
      cardiac catheterization, which was performed by two trained operators between
      January 2005 and June 2007. Procedural data were reported in a specific database.
      RESULTS: The procedural success rate through TRA (attempting one or both radial
      arteries) was 98.8%. One hundred and thirty-five radial attempts failed.
      Inability to puncture or to wire the artery accounted for 52.6% of failures,
      inability to reach coronary or graft ostia accounted for 20.7% and the remaining
      failures were related to the inability to reach a contralateral mammary graft. By
      multivariate analysis, the best predictors for failures were peripheral artery
      disease (PAD) (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.1-2.8; p =
      0.016), bedside clinical assessment of either a "small radial artery" size (OR
      2.6, 95% CI 1.4 to 5.0; p = 0.003) or a "difficult access" (OR 2.5, 95% CI 1.3
      4.9; p = 0.006). The number of failed attempts regresses annually by about 40%
      (OR 0.6, 95% CI 0.4-0.8; p < 0.001), thus demonstrating a continuous learning
      curve. Although rare, hematoma combined with swelling (3.8%) arises more
      frequently in females (OR 2.4, 95% CI 1.4-3.9; p = 0.001) and elderly patients
      (OR 1.9, 95% CI 1.0- 3.7; p = 0.040). CONCLUSION: The TRA can be safely proposed
      for all patients, with a low conversion rate to TFA when an attempt on both
      radial arteries is considered first.

PMID- 20814044
TI  - Left or right, transradial access for all.

PMID- 20814045
TI  - Right ventricular endocardial thermography in transplanted and coronary artery
      disease patients: first human application.
AB  - BACKGROUND: We sought to evaluate for the first time in humans the safety and
      feasibility of right ventricular (RV) thermography in patients with coronary
      artery disease (CAD) and in patients after heart transplantation (Tx), in
      comparison to subjects without structural heart disease (controls). METHODS:
      Ninety-one RV thermography procedures were performed in 16 patients with CAD, 19
      hearttransplant recipients and 6 patients without structural heart disease. We
      recorded the temperature of the RV intracavitary blood and RV endocardial septum,
      and calculated their difference using a dedicated commercially available
      thermography catheter. RESULTS: No complications were observed. CAD patients had
      a significantly higher temperature difference (0.19 +/- 0.11 degrees C) compared
      to both Tx patients (0.10 +/- 0.06 degrees C) and controls (0.07 +/- 0.04 degrees
      C) (p < 0.0001 and p = 0.003, respectively), whereas there was no significant
      difference between the Tx patients and controls (p = 0.65). CONCLUSION: RV
      thermography in humans is feasible and safe. Patients with stable CAD present a
      significantly higher temperature difference in the RV endocardium compared to
      controls; clinically stable transplant recipients have temperatures similar to
      controls. This novel method corroborates previous findings supporting the
      inflammatory hypothesis of coronary atherosclerosis.

PMID- 20814046
TI  - Parallel cholesterol crystals: a sign of impending plaque rupture?
AB  - BACKGROUND: Currently, there are no available methods that can reliably predict
      when or if an atheroma will rupture. Recent reports suggest cholesterol crystals
      (CCs), present within the necrotic core, are sharp and can penetrate and disrupt
      the fibrous cap, contributing to plaque rupture. Our aim is to show CC, normally
      distributed at random within the necrotic core, often develop a parallel
      configuration at the site of plaque disruption (PD) which may be a sign of
      impending plaque rupture. METHODS AND RESULTS: The coronary arteries of 83
      patients who died of acute coronary disease (ACD) were injected with a colored
      barium gelatin mass. The arteries were dissected, decalcified, cut at 2-3 mm
      intervals, and all segments mounted for microscopic study. All segments were
      reviewed to identify PDs and to determine the frequency of parallel cholesterol
      crystals (P-CCs) at the site of these PDs. There were 215 separate PDs in 83
      patients, with 64 (77%) patients showing more than one PD. P-CCs were present in
      126 (59%) of all PDs regardless of plaque size or the severity of luminal
      stenosis and were present with or without luminal thrombosis. Luminal thrombosis
      was present in 105 PDs (49%), primarily in those segments showing significant
      luminal stenosis. There was no significant difference in the frequency of luminal
      thrombosis in those PDs with or without P-CCs. CONCLUSIONS: P-CCs are commonly
      present at the site of PD and may contribute to PD by penetrating and disrupting
      the fibrous cap. The ability to recognize this parallel configuration may help to
      identify plaques with impending plaque rupture.

PMID- 20814047
TI  - Impact of measuring fractional flow reserve on decision-making in the cath lab in
      a cohort of patients being considered for coronary revascularization.
AB  - BACKGROUND: Fractional flow reserve (FFR) is an accepted standard to detect the
      functional significance of coronary stenoses. Recent trials suggest that
      revascularization of moderate coronary stenoses can be safely deferred if the FFR
      is > or = 0.75 and FFR can be used to guide therapy in multivessel disease. AIM:
      In a cohort of patients with moderate angiographic coronary disease, we sought to
      examine the influence of FFR on lesion revascularization and the impact of
      multivessel FFR assessment on revascularization strategy. METHODS AND RESULTS:
      Patients with FFR measurements taken between April 2005 to October 2007 were
      included. Out of 300 cases performed in this time, 264 patients were included.
      Patients were 62 +/- 11 years and 1.3 +/- 0.54 vessels were examined per case.
      92.7% of lesions with a FFR < 0.75 underwent revascularizati on an d 93% of
      lesions with a FFR > or = 0.75 had intervention deferred. FFR was 0.71 +/- 0.07
      in the revascularization group (9 coronary artery bypass graft surgery, 64
      percutaneous coronary interventions) and 0.86 +/- 0.06 in the deferred group (p <
      0.001). Overall, 75% of patients avoided revascularization of at least one vessel
      on the basis of the FFR. CONCLUSIONS: Measurement of FFR is clinically useful
      with a high impact on clinical decision-making in the catheterization laboratory.
      FFR can be used to reclassify patients with multivessel stenoses, reducing the
      need for revascularization in the majority of cases.

PMID- 20814048
TI  - Anatomy is destiny, but physiology is here today.

PMID- 20814049
TI  - The Angio-Seal Evolution registry: outcomes of a novel automated Angio-Seal
      vascular closure device.
AB  - OBJECTIVES: The objective of the study was to assess the efficacy and safety of a
      novel vascular closure device, the Angio-Seal Evolution (EVCD), in patients
      undergoing routine cardiac catheterization (CATH) and intervention (PCI) via a
      retrograde femoral artery access. BACKGROUND: Successful use of current
      generation vascular closure devices is highly dependent on operator methodology.
      To reduce dependence on operator technique, the EVCD was modified to automate the
      closure process, specifically the compaction of the extravascular collagen sponge
      that creates a sandwich under pressure against the intra-arterial anchor.
      METHODS: This was a prospective ten-site registry including 1,004 patients
      undergoing 1,010 procedures with in-laboratory closure using the EVCD after CATH
      and PCI. The primary outcome measure was the rate of major vascular
      complications, and secondary outcomes were deployment success, time to hemostasis
      and in-hospital rates of minor vascular complications through 30 days. Clinical
      trial identifier NCT 00817349. RESULTS: There were 575 CATH (56.9%) and 435 PCI
      (43.1%) closures. Overall deployment success was 99.7%; 99.8% for CATH and 99.5%
      for PCI. Major vascular complications occurred in 0.4% including 0.2% in CATH and
      0.7% in PCI. Minor vascular complications occurred in 2.4%, with 0.5% for CATH
      and 4.9% for PCI. CONCLUSIONS: Automation of the anchor-collagen closure of
      femoral artery access sites with the Angio-Seal ECVD resulted in excellent
      efficacy and safety after routine cardiac catheterization and intervention.

PMID- 20814050
TI  - An initiative to minimize amount of contrast media utilizing a novel rotational
      coronary sinus occlusive venography technique with ordinary cath-lab X-ray
      machine during CRT implantation.
AB  - BACKGROUND: Rotational angiography is one of the latest angiographic modalities
      to map the coronary venous tree anatomy. It provides a significant reduction in
      both contrast agent usage and radiation dose (up to 30%), without compromising
      the clinical utility of images. Hence, the present study was conducted to
      describe a new technique to minimize the amount of contrast media used during
      cardiac resynchronization therapy (CRT) implantation. METHOD: The SL3 sheath was
      inserted into the right atrium via the femoral vein followed by withdrawal of the
      dilator. The tip of the sheath was manipulated to the vicinity of the coronary
      sinus (CS) ostium (OS). The CS was entered using a deflated balloon catheter. The
      sheath was then advanced gently beyond the CS OS. Occlusive venography was
      performed using 5-8 ml of contrast media in a rotational view starting from 45
      degrees LAO to 0 degrees AP while holding the inflated balloon for a few seconds.
      RESULT: Data from 30 consecutive patients who underwent CRT implantation were
      analyzed. The feasibility of rotational angiography, while occluding the CS with
      a specialized long, preshaped sheath and using an ordinary cath-lab imaging
      machine, was supported by the correctly delineated CS anatomy of all patients
      without any complications and death related to the placement of the CS catheters
      or sheaths. The mean contrast dose used for the entire procedure in all patients
      undergoing CRT was 14.76 +/- 6.8 ml. CONCLUSION: Use of rotational CS occlusive
      venography utilizing an ordinary cath-lab X-ray machine minimizes the use of
      contrast media during CRT implantation without compromising the visualized
      anatomy.

PMID- 20814051
TI  - Preventing the unpreventable? Rotational angiography for the prevention of
      contrast-induced nephropathy.

PMID- 20814053
TI  - Tips and tricks for stenting of bifurcation coronary lesions.
AB  - Although the provisional stenting technique to treat coronary bifurcation lesions
      is the preferred method, many bifurcation lesions still require a two-stent
      technique to optimize the result and clinical outcome. This manuscript summarizes
      the tips and tricks of bifurcation stenting with cases illustrations. As
      interventionists are encountering more complex and difficult cases, one may find
      the tips and tricks in this manuscript helpful in daily practice.

PMID- 20814052
TI  - Comparison of acute vessel wall injury after self-expanding stent and
      conventional balloon-expandable stent implantation: a study with optical
      coherence tomography.
AB  - BACKGROUND: The acute impact in vivo from a selfexpanding stent on the vessel
      wall has not been sufficiently evaluated. OBJECTIVES: We sought to compare acute
      in vivo injury on the vessel wall and the clinical impact between a self
      expanding coronary stent and conventional balloon-expandable stents immediately
      after stent implantation. METHODS: We included 40 patients (45 vessels) with
      stable or unstable angina who were assigned to either the self-expanding stent
      (vProtect Luminal Shield) group (n = 9; Group 1) or the conventional balloon
      expandable stent group (n = 36; Group 2). Optical coherence tomography (OCT) was
      performed after stent deployment, as were qualitative and quantitative
      assessments of tissue prolapse, intrastent dissection, edge dissection and
      incomplete stent apposition. RESULTS: Tissue prolapse was visible in all vessels
      in both groups. The corrected tissue prolapse area by stent length was larger in
      Group 2 than in Group 1 (0.06 +/- 0.06 vs. 0.02 +/- 0.01 mm(2); p < 0.001).
      Intrastent dissection was more frequently seen in Group 2 (33/36 vs. 4/9 vessels;
      p = 0.004) and the mean length of the dissection flap was greater in Group 2 than
      in Group 1 (277.6 +/- 110.0 vs. 76.9 +/- 103.7 microm; p < 0.001). Although edge
      dissection was not detected in Group 1, it was visible in 19/36 vessels (52.8%)
      in Group 2. The frequency of incomplete stent apposition was not significantly
      different between Group 2 and Group 1 (23/36 vs. 7/9 vessels, p = 0.7), but the
      mean depth of incomplete stent apposition was greater in Group 2 than in Group 1
      (268.2 +/- 72.1 vs. 178.2 +/- 156.7 microm, p = 0.03). CONCLUSIONS: A
      selfexpanding stent was associated with less intrastent dissection and edge
      dissection than conventional balloon-expandable stents with OCT.

PMID- 20814054
TI  - Use of the venture wire control catheter for subintimal coronary dissection and
      reentry in chronic total occlusions.
AB  - Antegrade wiring of chronic total occlusions (CTO) may fail due to subintimal
      wire entry and inability to reenter the true lumen. We report the use of the
      Venture wire control catheter to reenter the true lumen after subintimal entry in
      a long right coronary artery CTO.

PMID- 20814055
TI  - Small balloon inflation over a jailed wire as a bailout technique in a case of
      abrupt side branch occlusion during provisional stenting.
AB  - During provisional stenting of a bifurcation lesion, recrossing into the side
      branch (SB) can be sometimes difficult or even impossible, especially when the SB
      lumen is compromised by a dissection. This report describes a rescue technique
      that can help to restore flow and regain access to the SB lumen in case of total
      SB occlusion after main vessel stent placement.

PMID- 20814056
TI  - Optical coherence tomography assessment of a coronary bare cobalt chromium stent
      deformed by the removal of an entrapped "jailed" guidewire.
AB  - A 64-year-old male with an ongoing acute coronary syndrome was treated
      percutaneously for a subtotal occlusion of a first diagonal branch. After
      predilatation of the diagonal, an important secondary branch was evident at the
      level of the subocclusion. A jailed wire was placed in this vessel, and stenting
      of the main diagonal branch was performed with a last-generation thin-strut bare
      cobalt-chromium stent. Conventional retrieval of the jailed wire was impossible,
      as the distal tip of the wire remained entrapped at the level of the stent. The
      strong pulling of the wire led only to a deep intubation of the guiding catheter
      with possible risk of dissection. Retrieval of the wire was finally possible with
      the support of an over-the-wire microcatheter. However, the stent, though still
      patent, appeared deformed. At a scheduled control angiogram 4 months later (while
      the patient was still asymptomatic), an optical coherence tomography (OCT)
      investigation of the stented segment confirmed the deformation of the stent. OCT
      showed a complete lack of stent struts on the side of origin of the secondary
      branch and an "overlap" or "accumulation" of several layers of stent struts on
      the other side. There were no signs of uncovered struts overall nor
      malapposition, and even the sites where multiple stent layers were visible were
      completely covered by neointimal hyperplasia. Despite the multiple layers of
      metal, the neointimal reaction was moderate and did not lead to a flow-limiting
      stenosis, thus the patient was further treated medically without the need for a
      new intervention.

PMID- 20814057
TI  - Fibrosing mediastinitis causing acute ostial left main myocardial infarction.
AB  - This report describes an unusual etiology of acute coronary syndrome. A 48-year
      old female presented with anginal chest discomfort and was found to have evidence
      of acute pulmonary edema requiring mechanical ventilation. She underwent
      emergency coronary angiography and stenting of the culprit left-main artery
      ostial discrete stenosis. Subsequent echocardiography and magnetic resonance
      imaging revealed severe aortic regurgitation and periaortic valve tissue
      infiltrates. Pericardiectomy and mediastinal mass biopsy were performed which
      indicated the pathology of fibrosing mediastinitis.

PMID- 20814058
TI  - The coronary anomaly: right coronary artery originates from the mid left anterior
      descending artery.
AB  - The most common coronary anomaly is the left circumflex artery (LCX) arising from
      the proximal right coronary artery (RCA). This variant is benign. The anomalous
      RCA often originates from the left sinus or from the proximal of the left main
      coronary artery. This case report presents a single coronary artery that is the
      RCA originating from the mid left anterior descending artery. The case is rare.
      We discuss how to make a accurate diagnosis and how to administer appropriate
      treatment.

PMID- 20814059
TI  - Two-stent telescoping technique for securing an atrially embolized venous stent.
AB  - Coronary sinus stenosis or atresia is a rare problem in congenital heart disease.
      It is sometimes associated with ventricular dysfunction. In this setting, relief
      of the obstruction may improve myocardial perfusion and contractility. During
      percutaneous stent deployment within the coronary sinus, distal embolization of
      the stent into the atrial chambers occurred. The patient had double inlet left
      ventricle, severe ventricular dysfunction, interrupted IVC, mechanical aortic
      valve, and a Fontan circulation. The intervention was performed as a rescue
      procedure prior to transplantation referral. In this report we describe use of
      telescoping technique, i.e., deploying the distal end of a long stent within the
      embolized stent while traversing its proximal end across the stenosed coronary
      sinus ostium. This secured the embolized stent and at the same time relieved the
      coronary sinus stenosis.

PMID- 20814060
TI  - Use of endovascular stent-graft repair for type B aortic dissection in polycystic
      kidney disease.
AB  - Aortic dissection (AD) is a life-threatening medical urgency with autosomal
      dominant polycystic kidney disease (ADPKD) being one of its major risk factors.
      Even though endovascular stentgraft repair has better outcomes in complicated
      Type B AD, its use in a patient with ADPKD has not been reported previously. This
      case involves a 44-year-old female with a history of ADPKD, hypertension and
      chronic low back pain presented with severe pain in the interscapular region. She
      was diagnosed with Type B AD by a computed tomographic (CT) scan of her chest and
      was managed medically. She was readmitted 9 days after discharge with worsening
      pain due to the proximal extension of AD. She was treated, with endovascular
      stentgraft repair sealing the dissection flap with significant subsequent
      reduction of the false lumen index and symptoms. We are reporting the first case
      of a complicated Type B AD in a patient with ADPKD managed with endovascular
      stent-graft repair.

PMID- 20814061
TI  - Successful intervention of an anomalous right coronary artery arising from the
      posterior left sinus of Valsalva.
AB  - Percutaneous coronary intervention (PCI) in an anomalous right coronary artery
      (RCA) arising from the left sinus of Valsalva can be technically difficult
      because selective cannulation of the vessel may not be easy. We present a case of
      two consecutive successful stent implantations in an anomalous RCA arising from
      the posterior left sinus of Valsalva. We used a Judkins left 5 guiding catheter,
      which provided excellent angiographic visualization and guide support for stent
      delivery throughout the procedure.

PMID- 20814062
TI  - Intravascular ultrasound images as an essential tool to assist left main
      operating strategy.
AB  - Intravascular ultrasound (IVUS) remains the only tool to understand, plan and
      evaluate complex lesions in percutaneous coronary intervention (PCI). Despite the
      evidence for left main intervention, 1 it is routinely used mainly to validate
      the final results in terms of optimal expansion of the stent. In this case
      report, we wish to highlight the role of IVUS guidance in the decision-making
      process throughout the PCI procedure.

PMID- 20814063
TI  - "Rendezvous in coronary" technique with the retrograde approach for chronic total
      occlusion.
AB  - Percutaneous coronary intervention (PCI) was performed for a chronic total
      occlusion (CTO) of the right coronary artery (RCA) in a 77-year-old male patient.
      A guidewire could not be passed through the vessel using the antegrade approach,
      so we tried the retrograde approach via a collateral septal channel. A Fielder FC
      guidewire (Asahi Intecc Co. Ltd., Aichi, Japan) was passed through the septal
      channel, and a Corsair catheter (Asahi Intecc) was advanced to the distal side of
      the CTO in the RCA. However, the guidewire could not be advanced from the false
      lumen to the true lumen using the kissing-wire technique (KWT) or the reverse
      controlled antegrade retrograde tracking (CART) technique. Therefore, we
      retracted the Corsair channel dilator for a #4PD and tried to advance the
      antegrade Conquest Pro guidewire (Asahi Intecc) from a straight subintimal site
      into the retrograde channel dilator catheter. After several attempts, the
      antegrade Conquest guidewire successfully entered the retrograde channel dilator
      catheter. Subsequently, a Cypher stent (Cordis Corp., Miami Lakes, Florida) was
      successfully placed. The "rendezvous in coronary" technique was useful for this
      CTO patient, in whom it was difficult to advance a guidewire into the true lumen
      by the KWT and CART techniques during the retrograde approach.

PMID- 20814064
TI  - Superoxide is a potential culprit of caspase-3 dependent endothelial cell death
      induced by lysophosphatidylcholine.
AB  - Oxidative stress in the vascular wall has intimately been implicated in the
      apoptosis of human umbilical vein endothelial cells (HUVECs) by
      lysophosphatidylcholine (LPC). However, the major type of reactive oxygen species
      (ROS) in this apoptotic signaling pathway remains to be clarified. In this study,
      we report that superoxide mediate LPC-induced caspase-3 dependent apoptosis in
      cultured HUVECs. The stimulation of HUVECs with LPC evoked apoptosis and ROS
      generation, and inhibited nitric oxide (NO) production in a dose-dependent
      manner. The classical caspase-3 dependent apoptosis was determined after 16 hours
      treatment by Western blotting using an antibody against cleaved caspase-3. The
      caspase-3 activation induced by LPC was prominently inhibited by antioxidants or
      NO donors and enhanced by NO inhibitors. Especially, LPC-induced caspase-3
      activation was inhibited by superoxide dismutase (SOD) and enhanced by ammonium
      tetrathiomolybdate, SOD inhibitor. Additionally, xanthine/xanthine oxidase
      mixture increased the caspase-3 activation but catalase failed to reduce this
      superoxide-induced caspase-3 activation. These findings indicate that the
      superoxide generation caused by LPC activates the caspase-3 which results in
      HUVECs death. This study reveals some evidences linking superoxide with caspase-3
      activation and provides a new dimension to superoxide-mediated caspase-3
      activation in developing the endothelial dysfunction and atherosclerosis.

PMID- 20814065
TI  - Ghrelin signaling in human mesenteric arteries.
AB  - The hypothesis is that the ghrelin signal pathway consists of new participants
      including a local second mediator in human mesenteric arteries. The contractile
      force of isometric artery preparations was measured using a wire-myograph. Whole
      cell patch clamp experiments were performed on freshly isolated single smooth
      muscle cells from the same tissue. After the addition of ghrelin (100 nmol) the
      outward potassium currents conducted through iberiotoxin-sensitive calcium
      activated potassium channels with a large conductance were almost entirely
      abolished. The effect of ghrelin on potassium currents was insensitive to
      selective inhibitors of cAMP-dependent protein kinase and soluble guanylate
      cyclase, but was eliminated in the presence of des-octanoyl ghrelin and O
      (octahydro-4,7-methano-1H-inden-5-yl) carbonopotassium dithioate (D-609). Ghrelin
      dose-dependently increased the force of contraction of native, endothelium
      denuded and mostly of endothelium-denuded and treated with tetrodotoxin human
      mesenteric arteries preconstricted with 1 nmol endothelin-1. This effect of
      ghrelin was blocked when the bath solution contained 1,4-diamino-2,3-dicyano-1,4
      bis(2-aminophenylthio)butadiene (U0126), 4-amino-5-(4-methylphenyl)-7-(t-butyl)
      pyrazolo[3,4-d] pyrimidine (PP2), D-609, 2-[1-(3-dimethylaminopropyl)indol-3-yl]
      3-(indol-3-yl) maleimide (GF109203x), pertussis toxin, 2-aminoethyl
      diphenylborinate (2-APB), indomethacin, (5Z,13E)-(9S,11S,15R)-9,15,Dihydroxy-11
      fluoro-15-(2-indanyl)-16,17,18,19,20,pentanor-5,13-prostadienoic acid (AL-8810) -
      a non-selective prostanoid receptor antagonist, 5-(4-Chlorophenyl)-1-(4
      methoxyphenyl)-3-trifluoromethyl pyrazolo (SC-560) - a selective cyclooxygenase 1
      inhibitor, ozagrel - a selective thromboxane A(2) synthase inhibitor or T
      prostanoid receptor antagonist GR32191B. It is concluded that ghrelin increases
      the force of contraction of human mesenteric arteries by a novel mechanism that
      involves Src kinase, mitogen-activated protein kinase kinase (MEK),
      cyclooxygenase 1 and T prostanoid receptor agonist, most probably thromboxane
      A(2).

PMID- 20814066
TI  - The alpha2-adrenoceptors do not modify the activity of tyrosine hydroxylase,
      corticoliberine, and neuropeptide Y producing hypothalamic magnocellular neurons
      ion the Long Evans and Brattleboro rats.
AB  - The hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei are activated
      by body salt-fluid variations. Stimulation of alpha(2)-adrenoceptors by an
      agonist-xylazine (XYL) activates oxytocinergic but not vasopressinergic
      magnocellular neurons. In this study, tyrosine hydroxylase (TH), corticoliberine
      (CRH), and neuropeptide Y(NPY) magnocellular phenotypes, were analysed in
      response to alpha(2)-adrenoceptor manipulations and sustained hyperosmolality in
      vasopressin deficient homozygous Brattleboro (di/di) rats. Saline (0.9% NaCl, 0.1
      ml/100g/bw), XYL (10 mg/kg/bw), atipamezole (ATIP, alpha(2)-adrenoceptors
      antagonist, 1 mg/kg/bw), and ATIP 5 min later followed by XYL, were applied
      intraperitoneally. Presence of immunolabeled Fos peptide signalized the neuronal
      activity. Ninety minutes after injections, the rats were anesthesized and
      sacrificed by transcardial perfusion with fixative. Coronal sections of 30 mum
      thickness double immunolabeled with Fos/neuropeptide were evaluated under light
      microscope. Under basal conditions, di/di in comparison with control Long Evans
      rats, displayed significantly higher number of TH, CRH, and NPY immunoreactive
      neurons in the SON and PVN (except NPY cells in PVN) and more than 90%, 75%, and
      86% of TH, NPY, and CRH neurons, respectively, displayed also Fos signal in the
      SON. XYL did not further increase the number of Fos in the PVN and SON and ATIP
      failed to reduce the stimulatory effect of hypertonic saline in all neuronal
      phenotypes studied. Our data indicate that hyperosmotic conditions significantly
      influence the activity of TH, CRH, and NPY magnocellular neuronal phenotypes, but
      alpha(2)-adrenoceptors do not play substantial role in their regulation during
      osmotic challenge induced by AVP deficiency.

PMID- 20814068
TI  - Cyclooxygenase-2 (COX-2) is the key event in pathophysiology of Barrett's
      esophagus. Lesson from experimental animal model and human subjects.
AB  - Mixed reflux of the gastroduodenal contents induces the esophageal mucosal damage
      and inflammation progressing chronic esophagitis and premalignant Barrett's
      esophagus (BE). The role of cyclooxygenase-2 (COX-2) and chronic inflammation in
      the progression of BE toward adenocarcinoma of the esophagus has not been
      extensively studied in experimental models of BE in animals and in human
      subjects. We evaluated the expression of COX-2 in rat model of BE and examined
      the usefulness of COX-2 expression in determining the risk of malignant
      transformation in patients with BE treated with argon plasma coagulation (APC)
      that allows for effective ablation of metaplastic mucosa (group A) without or
      with proton pump inhibitors (PPI). In addition, the group B of patients was
      subjected to laparoscopic Nissen's fundoplication and group K that served as
      control, received PPI treatment only. Expression of COX-2 was evaluated in fresh
      frozen biopsy specimens obtained from the distal esophagus in all 60 patients
      before and 12 months after treatment. In experimental studies, eighty rats were
      surgically prepared with esophagogastroduodenal anastomosis (EGDA) resulting in
      chronic esophagitis. At 4 months, the esophageal damage in EGDA rats was
      evaluated by macroscopic and histological index score, the plasma IL-1beta and
      TNF-alpha levels was determined by ELISA and the mucosal expression of COX-2 mRNA
      and COX-2 protein were assessed by RT-PCR and Western Blot, respectively. Chronic
      esophagitis was developed in all EGDA animals followed by the rise in the plasma
      TNF-alpha and IL-1beta levels. Histology revealed extensive esophageal
      ulcerations with development of columnar epithelium, formation of mucus glands in
      squamous epithelium, intestinal metaplasia distant to anastomosis consisting of
      goblet cells, infiltration of inflammatory cells including plasma cells and
      lymphocytes. COX-2 mRNA was absent in the esophageal mucosa of sham-control
      animals but strongly upregulated in metaplastic Barrett's epithelium. In BE
      patients, the overexpression of COX-2 was documented in patients with dysplasia.
      After APC (group A) or Nissen's fundoplication (group B), the expression of COX-2
      mRNA was markedly reduced and these effects were positively correlated with
      histopathological findings. Controls failed to show significant alterations in
      COX-2 expression. We conclude that 1) EGDA rats serve as the suitable model of
      the chronic esophagitis by the gastrointestinal refluxate resembling many
      features of those observed in human Barrett's esophagus, as confirmed by severe
      morphology changes, excessive release of proinflammatory cytokines TNF-alpha and
      IL-1beta and overexpression of COX-2, and 2) the significant correlation of the
      degree of COX-2 overexpression with histopathological findings indicates the
      usefulness of this inducible biomarker as a valuable indicator of the risk of
      malignant transformation in patients with BE.

PMID- 20814067
TI  - Selective central activation of somatostatin receptor 2 increases food intake,
      grooming behavior and rectal temperature in rats.
AB  - The consequences of selective activation of brain somatostatin receptor-2 (sst2)
      were assessed using the sst2 agonist, des-AA(1,4-6,11-13)
      [DPhe(2),Aph7(Cbm),DTrp(8)]-Cbm-SST-Thr-NH2. Food intake (FI) was monitored in ad
      libitum fed rats chronically implanted with an intracerebroventricular (i.c.v.)
      cannula. The sst(2) agonist injected i.c.v. at 0.1 and 1 microg/rat dose
      dependently increased light phase FI from 2 to 6 hours post injection (2.3+/-0.5
      and 7.5+/-1.2 respectively vs. vehicle: 0.2+/-0.2 g/300 g bw, P<0.001). Peptide
      action was reversed by i.c.v. injection of the sst2 antagonist, des-AA(1,4-6,11
      13)-[pNO(2)-Phe(2),DCys(3),Tyr(7),DAph(Cbm)8]-SST-2Nal-NH(2) and not reproduced
      by intraperitoneal injection (30 microg/rat). The sst(2) antagonist alone i.c.v.
      significantly decreased the cumulative 14-hours dark phase FI by 29.5%. Other
      behaviors, namely grooming, drinking and locomotor activity were also increased
      by the sst(2) agonist (1 microg/rat, i.c.v.) as monitored during the 2(nd) hour
      post injection while gastric emptying of solid food was unaltered. Rectal
      temperature rose 1 hour after the sst(2) agonist (1 microg/rat, i.c.v.) with a
      maximal response maintained from 1 to 4 hours post injection. These data show
      that selective activation of the brain sst(2) receptor induces a feeding response
      in the light phase not associated with changes in gastric emptying. The food
      intake reduction following sst(2) receptor blockade suggests a role of this
      receptor in the orexigenic drive during the dark phase.

PMID- 20814069
TI  - Therapeutic effect of ghrelin in the course of cerulein-induced acute
      pancreatitis in rats.
AB  - Recent studies have shown that pretreatment with ghrelin exhibits protective
      effect in the gut. Administration of ghrelin reduces gastric mucosal damage, as
      well as inhibits the development of experimental pancreatitis. However, this
      protective effect requires administration of ghrelin before gastric or pancreatic
      damage and thus has a limited clinical value. The aim of present study was to
      assess the influence of ghrelin administered after development of acute
      pancreatitis on the course of this disease. Acute pancreatitis was induced by
      cerulein. Ghrelin was administered twice a day for 1, 2, 4, 6 or 9 days at the
      dose of 4, 8 or 16 nmol/kg/dose. The first dose of ghrelin was given 24 hours
      after last injection of cerulein. The severity of acute pancreatitis was assessed
      between 0 h and 10 days after cessation of cerulein administration.
      Administration of caerulein led to the development of acute edematous
      pancreatitis and maximal severity of this disease was observed 24 hours after
      induction of pancreatitis. Treatment with ghrelin reduced morphological signs of
      pancreatic damage such as pancreatic edema, leukocyte infiltration and
      vacuolization of acinar cells, and led to earlier regeneration of the pancreas.
      Also biochemical indexes of the severity of acute pancreatitis, serum activity of
      lipase and amylase were significantly reduced in animals treated with ghrelin.
      These effects were accompanied by an increase in the pancreatic DNA synthesis and
      a decrease in serum level of pro-inflammatory interleukin-1b. Administration of
      ghrelin improved pancreatic blood flow in rats with acute pancreatitis. We
      conclude that: (1) treatment with ghrelin exhibits therapeutic effect in
      caerulein-induced experimental acute pancreatitis; (2) this effect is related, at
      least in part, to the improvement of pancreatic blood flow, reduction in
      proinflammatory interleukin-1beta and stimulation of pancreatic cell
      proliferation.

PMID- 20814070
TI  - Gastric ulcer healing and stress-lesion preventive properties of pioglitazone are
      attenuated in diabetic rats.
AB  - Diabetes mellitus increases susceptibility to acute gastric injury and impairs
      ulcer healing. Pioglitazone as an agonist of peroxisome proliferator-activated
      receptor gamma (PPARgamma) is used as anti-diabetic drug and has additionally
      gastroprotective activities. However, the effect of pioglitazone on the
      protection and healing of gastric mucosa under diabetic conditions is poorly
      understood. The aim of the present study was: 1) to compare the effects of
      treatment with PPARg ligand (pioglitazone) on healing of acetic acid-induced
      gastric ulcers and prevention of acute water immersion and restraint stress (WRS)
      induced gastric lesions in normal rats and those with streptozotocin (STZ)
      induced diabetes mellitus; 2) to assess the effects of pioglitazone on the mRNA
      expression of cyclooxygenase-2 (COX-2), c-NOS, interleukin-1beta and hypoxia
      inducible factor-1 alpha (HIF-1alpha) in the gastric mucosa of rats with or
      without STZ-induced diabetes mellitus; 3) to investigate the involvement of
      endogenous NO and proinflammatory cytokines (IL-1beta, TNF-alpha) in healing of
      chronic gastric ulcers and in prevention of acute stress lesions by pioglitazone
      in rats with or without STZ-induced diabetes mellitus. Diabetes was induced in
      rats by single injection of STZ (70 mg/kg i.p.) four weeks prior to production of
      gastric ulcers by acetic acid method or induction of stress lesions by 3.5 hours
      of WRS. Non-diabetic rats were used as controls. Two major animal groups (A and
      B) were tested; A) diabetic and non-diabetic rats with chronic gastric ulcers
      treated with 1) pioglitazone (40 mg/kg-d i.g.), 2) pioglitazone in combination of
      blocker of NO synthase (L-NNA 20 mg/kg-d i.p.), and 3) saline (vehicle-control);
      and B) diabetic and non-diabetic rats exposed to 3.5 hours of WRS and pretreated
      with 1) pioglitazone (40 mg/kg i.g.), 2) pioglitazone in combination of blocker
      of NO synthase (L-NNA 20 mg/kg i.p.), and 3) saline (vehicle-control). The
      gastric mucosal blood flow was assessed by H(2)-gas clearance method. The area of
      chronic acetic acid ulcers and number of acute WRS-induced gastric lesions were
      assessed by planimetry or by counting of number of lesions, respectively. In rats
      with chronic ulcers, the mRNA expression of HIF-1alpha, IL-1beta and COX-2 was
      assessed by RT-PCR and protein expression of platelet endothelial cell adhesion
      molecule-1 (PECAM-1), COX-2 and cNOS was examined by Western blot. In rats with
      stress lesions, the protein expression of COX-2, cNOS, catalase, PPAR and heat
      shock protein 70 (HSP70) was examined by Western blot. In diabetic rats, a marked
      delay in ulcer healing and increased susceptibility to WRS lesions were observed
      and these effects were accompanied by a significant decrease in GBF. Pioglitazone
      significantly increased healing of chronic gastric ulcers and exerted a strong
      protective effect against WRS-induced lesions, but these effects were attenuated
      by NO-inhibition with L-NNA. Interestingly, the ulcer healing and
      gastroprotective effects of pioglitazone were weak under diabetic conditions, and
      this effect on ulcer healing was accompanied by impaired angiogenesis due to
      decreased PECAM-1 expression, attenuated expression of COX-2 and the increased
      expression of proinflammatory cytokines compared to those in diabetic rats
      treated with vehicle. We conclude that: 1) experimental diabetes in rats impairs
      healing of chronic ulcers and enhances acute stress lesions due to an increase in
      the expression and release of proinflammatory cytokines such as TNF-alpha and IL
      1beta; 2) the ulcer healing effect of pioglitazone, which is, at least in part,
      mediated by endogenous NO, is significantly attenuated by L-NNA in diabetic rats
      despite increased COX-2 expression at the ulcer edge; 3) the formation of acute
      gastric lesions induced by WRS is also attenuated by pretreatment with
      pioglitazone due to increased GBF probably mediated by NO, as the administration
      of L-NNA reversed, in part, the preventive action induced by this PPARgamma
      ligand, and 4) pioglitazone is effective both in healing of chronic ulcers and
      protection against WRS lesions though its action under diabetic conditions seems
      to be attenuated, possibly due to reduction in NOS-NO system, angiogenesis and
      increased expression and release of proinflammatory cytokines.

PMID- 20814071
TI  - Helicobacter pylori lipopolysaccharide activity in human peripheral blood
      mononuclear leukocyte cultures.
AB  - Helicobacter pylori (H. pylori) have been recognized as a major cause of chronic
      gastritis, gastric and duodenal ulcers and gastric cancer. Macrophages are the
      targets of lipopolysaccharide (LPS), which is a constituent of the outer membrane
      of Gram-negative rods. In this study we focused on a potential role of
      macrophages in the proliferation of human peripheral blood mononuclear leukocytes
      (PBML) in the milieu of H. pylori LPS and standard E. coli LPS. First, we found
      that H. pylori and E. coli LPS induced proliferation of total PBML (tPBML) from 5
      out 21 healthy blood donors (LPS responders). In the LPS milieu, tPBML from the
      majority of volunteers (LPS non-responders) showed a significant decrease in the
      [(3)H]-thymidine incorporation as compared to tPBML in medium alone. The
      decreased cell proliferation was associated with a diminished metabolic activity
      of non-adherent lymphocytes. Then, non-adherent lymphocytes were stimulated with
      autologous macrophages pulsed with bacterial LPS. Still, the lymphocytes from the
      non-responders did not proliferate in the cultures with LPS exposed macrophages.
      In the group of LPS responders, the macrophages pulsed with H. pylori LPS
      significantly reduced the proliferation of non-adherent lymphocytes. The possible
      mechanism regulating the responses of PBML to bacterial LPS with an implication
      for the outcome of H. pylori infections is discussed.

PMID- 20814072
TI  - Importance of ghrelin in hypothalamus-pituitary axis on growth hormone release
      during normal pregnancy in the rat.
AB  - Ghrelin is a hormone mainly produced in the stomach and its first discovered
      action was connected with regulating growth hormone secretion. It was found that
      ghrelin injection increases growth hormone release and that this action is dose
      dependent. Ghrelin may influence growth hormone secretion both by central and
      peripheral action. Ghrelin acts via its receptors named growth hormone
      secretagogue receptors (GHSR). Ghrelin receptors were found in almost all tissues
      including the central nervous system. Besides influence on growth hormone
      secretion, ghrelin also regulates food intake and energy metabolism centrally as
      well as peripherally. In our study, active ghrelin and growth hormone levels in
      serum were measured. We also investigated gene expression of proghrelin, growth
      hormone releasing hormone (GHRH) and growth hormone receptor (GH-R) in the
      hypothalamus and the active form of ghrelin receptor (GHSR-1a) in hypothalamus
      and pituitary. Expression of growth hormone and growth hormone releasing hormone
      receptor (GHRH-R) in the pituitary were also measured. The results of our study
      indicate that active ghrelin and growth hormone levels in serum increased during
      pregnancy. Expression of ghrelin in hypothalamus and its receptor also increased
      in hypothalamus and pituitary during pregnancy. We also observed that growth
      hormone gene expression rose in pituitary, while its receptor mRNA level in
      hypothalamus decreased. Additionally, growth hormone expression in placenta
      decreased during pregnancy. Moreover, GHRH in hypothalamus and its receptor in
      pituitary showed reduced levels during pregnancy. Our results may indicate that
      ghrelin is a important factor influencing growth hormone release during
      pregnancy.

PMID- 20814073
TI  - ERK 1/2 and PI-3 kinase pathways as a potential mechanism of ghrelin action on
      cell proliferation and apoptosis in the porcine ovarian follicular cells.
AB  - Recently, we reported the stimulatory effect of ghrelin on ovarian cell
      proliferation in parallel with the inhibitory action of ghrelin on cell
      apoptosis. The aim of the presented data propose local activation of
      extracellular signal-regulated protein kinase 1 and 2 (ERK 1/2) and
      phosphoinositide-3 (PI-3) kinase pathways as a mechanism of ghrelin effect in the
      porcine ovary. To test this hypothesis, action of ghrelin on levels of ERK 1/2
      with PI-3 kinase activity and protein expression using ELISA and western blot
      analysis, respectively, was examined. Additionally, to determine which pathways
      (ERK 1/2 or PI-3 kinase) are the potential signals of ghrelin-mediated cell
      proliferation and apoptosis in ovarian cells, we used PD098059 (50 microM) and
      wortmannin (200 microM), well-known inhibitors of these kinases. Treatment of
      ovarian coculture cells with ghrelin (100, 250, 500 and 1000 pg/ml) showed
      stimulation of phospho-ERK 1/2 levels and PI-3 kinase activity, with the maximum
      effect observed after 15 min of cell incubation. Additionally, western blot
      analysis indicated that ghrelin increased expression of both kinases. Moreover,
      ghrelin used in combination with PD098059 or wortmannin significantly decreased
      cell proliferation, which was measured by the Alamar Blue assay and increased
      apoptosis, which was measured by caspase - 3 activity and DNA fragmentation. In
      conclusion, these results suggest that the ERK 1/2 and PI-3 kinase pathways may
      be potential signals of ghrelin mediate the cell proliferation and apoptosis of
      ovary cells.

PMID- 20814074
TI  - Vasopressin release from the rat hypothalamo-neurohypophysial system: effects of
      gonadotrophin-releasing hormone (GnRH), its analogues and melatonin.
AB  - The influence of gonadotrophin-releasing hormone (GnRH) and its analogues (i.e.,
      agonist and antagonist) on vasopressin (VP) release from the rat hypothalamo
      neurohypophysial (H-N) system was studied both in vitro and in vivo.
      Additionally, it was determined whether the possible response of vasopressinergic
      neurones to these peptides could be modified by melatonin through a cAMP
      dependent mechanism. In this study we demonstrate, for the first time, that the
      highly selective GnRH agonist (i.e., [Des-Gly(10),D-His(Bzl)(6),Pro-NHEt(9)]
      LHRH; histrelin) stimulates the release of VP from the rat H-N system, while
      native GnRH and its antagonist remain inactive in modifying this process in
      vitro. Melatonin significantly inhibited basal and histrelin-induced release of
      VP in vitro, but displayed no significant influence on VP secretion when GnRH or
      its antagonist were present in a medium. Melatonin fully suppressed forskolin
      stimulated VP release from the rat H-N system. On the other hand, addition of
      forskolin to a medium containing both histrelin and melatonin did not further
      alter the inhibitory influence of melatonin on the histrelin-dependent release of
      VP in vitro. After intracerebroventricular (i.c.v.) infusion of native GnRH or
      its agonist, blood plasma VP concentration was significantly higher than in
      control animals, which was accompanied by decreased content of the hormone in the
      neurohypophysis. Intravenous (i.v.) injection of melatonin did not change, in any
      subgroup, blood plasma VP concentration, when compared to the vehicle-injected
      rats. However, the neurohypophysial levels of the hormone were significantly
      higher after melatonin injection in control, GnRH- and histrelin-infused animals.
      Our present results suggest that activation of the GnRH receptor in the
      hypothalamus is involved in stimulation of VP secretion from the rat H-N system.
      We have also shown that melatonin, at a concentration close to its physiological
      level in the blood, significantly reduces the in vitro response of
      vasopressinergic neurones to a GnRH agonist - histrelin; this effect of melatonin
      could be mediated through intracellular processes that involve, among others, the
      cAMP-dependent mechanism.

PMID- 20814075
TI  - Sesbania grandiflora diminishes oxidative stress and ameliorates antioxidant
      capacity in liver and kidney of rats exposed to cigarette smoke.
AB  - Cigarette smoke is a major risk factor for many chronic diseases. However, it may
      be possible to relieve the smoke-induced damage by increasing the defensive
      system. In this study, we planned to evaluate the protective mechanism of
      Sesbania grandiflora (S. grandiflora) leaves against cigarette smoke-induced
      oxidative damage in liver and kidney of rats. Adult male Wistar-Kyoto rats were
      exposed to cigarette smoke for a period of 90 days and consecutively treated with
      S. grandiflora aqueous suspension (SGAS, 1000 mg/kg body weight per day by oral
      gavage) for a period of 3 weeks. Hepatic marker enzymes like aspartate
      aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase
      (ALP), as well as renal markers such as urea and creatinine were analysed in
      serum. Lipid peroxidation marker mainly thiobarbituric acid reactive substances
      (TBARS) and antioxidant enzymes namely superoxide dismutase (SOD), catalase
      (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S
      transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH) activities and
      non-enzymatic antioxidants such as reduced glutathione, ascorbic acid and alpha
      tocopherol levels were studied. In addition, micronutrients mainly copper (Cu),
      zinc (Zn), manganese (Mn) and selenium (Se) levels were analyzed in liver and
      kidney of rats exposed to cigarette smoke. The results indicated that SGAS
      significantly decreased the elevated hepatic, renal and lipid peroxidation
      markers and ameliorated the diminished antioxidant levels while restored the
      hepatic and renal architecture in cigarette smoke-exposed rats. This study
      concludes that S. grandiflora leaves restrain cigarette smoke-induced oxidative
      damage in liver and kidney of rats.

PMID- 20814076
TI  - Functional, histological structure and mastocytes alterations in rat urinary
      bladders following acute and [corrected] chronic cyclophosphamide treatment.
AB  - Neurogenic inflammation is linked to urinary bladder overactivity development.
      Cyclophosphamide (CYP) damages all mucosal defence lines of urinary bladder and
      induces cystitis with overactivity. The aim of this study was to estimate the
      effect of CYP on rat urinary bladder function, histological structure and
      mastocytes numbers following acute and chronic CYP treatment. Fourty two female
      rats were divided into four groups: I (control), II (acute cystitis), III
      (chronic cystitis), IV (sham group). Acute and chronic cystitis were induced by
      CYP in single dose and four doses (1(st), 3(rd), 5(th), 7(th) day), respectively.
      In group I-III the cystometric evaluation was performed. Sections of the bladder
      were stained with HE and toluidine blue for the detection of mastocytes. The
      severity of inflammation was examined according to mucosal abrasion, haemorrhage,
      leukocyte infiltration and oedema. Acute and chronic CYP treatment caused
      inflammatory macroscopic and microscopic changes (mucosal abrasion, haemorrhage,
      oedema) and increased infiltration of inflammatory cells in urinary bladder.
      Acute treatment induced the infiltration of mastocytes within bladder wall
      contrary to chronic one decrement. Acute treatment caused more severe mucosal
      abrasion, whereas chronic one revealed more developed haemorrhage changes.
      Additionally, cystometric evaluation revealed urinary bladder overactivity
      development in both types of cystitis. Basal pressure and detrusor overactivity
      index after acute treatment increased considerably in comparison with the
      increase obtained after chronic one. Our results proved that acute model of CYP
      induced cystitis in rats is more credible for further evaluation of neurogenic
      inflammation response in pathogenesis of overactive bladder as compared to
      chronic one.

PMID- 20814077
TI  - Systemically active human opiorphin is a potent yet non-addictive analgesic
      without drug tolerance effects.
AB  - Human opiorphin QRFSR-peptide protects enkephalins from degradation by human
      neutral endopeptidase (hNEP) and aminopeptidase-N (hAP-N) and inhibits pain
      perception in a behavioral model of mechanical acute pain (1). Here, using two
      other pain rat models, the tail-flick and the formalin tests, we assess the
      potency and duration of the antinociceptive action of opiorphin with reference to
      morphine. The occurrence of adverse effects with emphasis on the side-effect
      profile at equi-analgesic doses was compared. We demonstrate that opiorphin
      elicits minimal adverse morphine-associated effects, at doses (1-2 mg/kg, i.v.)
      that produce a comparable analgesic potency in both spinally controlled thermal
      induced acute and peripheral chemical-induced tonic nociception. The analgesic
      response induced by opiorphin in the formalin-induced pain model preferentially
      requires activation of endogenous mu-opioid pathways. However, in contrast to
      exogenous mu-opioid agonists such as morphine, opiorphin, does not develop
      significant abuse liability or antinociceptive drug tolerance after subchronic
      treatment. In addition, anti-peristaltism was not observed. We conclude that
      opiorphin, by inhibiting the destruction of endogenous enkephalins, which are
      released according to the painful stimulus, activates restricted opioid pathways
      specifically involved in pain control, thus contributing to a greater balance
      between analgesia and side-effects than found with morphine. Therefore, opiorphin
      could give rise to new analgesics endowed with potencies similar to morphine but
      with fewer adverse effects than opioid agonists. Its chemical optimization, to
      generate functional derivatives endowed with better bioavailability properties
      than the native peptide, could lead to a potent class of physiological type
      analgesics.

PMID- 20814078
TI  - Adenosine 5'-triphosphate is the predominant source of peripheral adenosine in
      human B lymphoblasts.
AB  - Adenosine 5'-triphosphate (ATP) and adenosine are the crucial endogenous
      signaling molecules in immunity and inflammation. In this study we identified the
      source of extracellular adenosine in human B lymphoblasts, and evaluate the ATP
      release and metabolism. We observed that the B cells continuously released
      substantial quantities of ATP (35 pmol/10(6) cells) when subjected to slow motion
      in the incubation medium. The adenosine level in the B cell incubation medium was
      very low, and increased (5-fold) upon inhibition of adenosine deaminase activity
      with 10 muM of 2-deoxycoformycin (DCF). Inclusion of an inhibitor of equilibrate
      nucleoside transport (nitrobenzylthioinosine) in the incubation medium in the
      presence of DCF resulted in the elevation of adenosine level by 9-fold.
      Inhibition of ecto-ATPase activity with 100 muM of ARL67156 was associated with a
      2-fold increase of the extracellular ATP level and a 3-fold decrease of adenosine
      concentration in the cell culture media. Inclusion of alpha,alpha
      methyleneadenosine 5'-diphosphate, a selective inhibitor of ecto-5'-nucleotidase
      in the incubation medium resulted in a significant decrease (7-fold) the
      adenosine concentration. In conclusion, our results indicate that ATP released
      from the B cell is the primary source of peripheral adenosine, and that the
      activities of ecto enzymes and the efficiency of Ado uptake through the
      nucleoside transporters determine the Ado level on the B cell surface.

PMID- 20814079
TI  - GABAergic and glutamatergic currents in hippocampal slices and neuronal cultures
      show profound differences: a clue to a potent homeostatic modulation.
AB  - Acute hippocampal slices and primary neuronal cultures are often used with a
      tacit assumption that basic characteristics of the two models closely resemble
      each other. The use of the cell cultures, however, may raise controversies
      because of non-physiological conditions resulting from e.g. glial cells deficit,
      random neuronal sprouting, lack of specificity in the synaptic connections,
      impaired homeostasis, etc. Importantly, alteration in neuronal environment,
      especially when occurring over a prolonged period of time, may give rise to a
      profound homeostatic modulation. In the present study we have compared the
      properties of GABAergic and glutamatergic (non-NMDA) currents in pyramidal
      neurons from hippocampal slices and neuronal cell culture. We show that, most
      strikingly, amplitude ratio of currents elicited by ultrafast applications of
      saturating GABA and glutamate was nearly one order of magnitude larger in
      cultured neurons than that in slices. Miniature IPSCs and EPSCs also showed
      substantial differences between these two models. In particular, mEPSC amplitudes
      were larger and more frequent in cultured neurons but their time duration was
      longer in slices. Miniature IPSCs did not show differences in amplitude when
      comparing slices and cultures but their time duration was faster and occurrence
      more frequent in slices. In conclusion, we provide evidence that expression
      pattern of GABA(A) and glutamate receptors as well as synaptic current properties
      in the neuronal cell culture show profound differences with respect to that in
      the physiological conditions.

PMID- 20814080
TI  - Comparative analyses of different surfactants on matrix-assisted laser
      desorption/ionization mass spectrometry peptide analysis.
AB  - Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been
      extensively used for proteomics and peptidomics analysis. Nevertheless, these
      analyses, when focused on low molecular mass proteins, show some limitation due
      to background interference from surfactant ions. Surfactants are routinely used
      as a solubilizing or denaturing agents for proteins and peptides. In this report,
      an evaluation and further comparison of the effects of an ionic surfactant,
      sodium dodecyl sulfate (SDS), and a non-ionic surfactant, tergitol, on MALDI-MS
      analyses of the amphipathic peptides, angiotensin and bradykinin, were carried
      out. At concentrations > or = 10 mmol L(-1), SDS deteriorates the MALDI spectral
      quality by reducing the signal and intensity of the analyte ions. In particular,
      it affects the hydrophobic peptide where the signal of surfactant-interfering
      ions suppresses the analyte ion signal. Whereas, the non-ionic surfactant,
      tergitol, improves the MALDI-MS analysis of peptide mixtures or hydrophobic
      peptides by reducing interference from the surfactant itself in positive ion mode
      analysis. Three-dimensional molecular modeling of two different peptides in
      complex to tergitol NP-40 and SDS were conducted in order to explain the
      molecular effects of both agents. In summary, while SDS must be removed from the
      sample solution to avoid interference of ions from SDS and suppression of analyte
      ion signal, tergitol at low concentrations may be used as an additive with sample
      solution for MALDI-MS analysis of peptides. Finally, molecular modeling analyses
      associated with docking were used in order to explain experimental biochemical
      data.

PMID- 20814081
TI  - Cytidine-Ag+-purine base complexes as studied by electrospray ionization mass
      spectrometry.
AB  - The complexes of cytidine (C) with Ag(+) and adenosine (A), guanosine (G),
      inosine (In) and caffeine (Caf) were studied by electrospray ionization mass
      spectrometry (ESI-MS). Both collision-induced dissociation (CID) "in- source" and
      CID MS/MS experiments were performed. The stability of [C + G + Ag](+) and [C +
      In + Ag](+) ions in the gas phase was found to be much higher than that of [C + A
      + Ag](+) and [C + Caf + Ag](+) ions. It is reasonable to conclude that guanosine
      and inosine form bidentate complex with silver cation, by N7 atom and O=C6 oxygen
      atom, whereas adenosine and caffeine form monodentate complexes, by N3 atom of
      adenine and N9 atom of caffeine.

PMID- 20814082
TI  - Comparison of humic substances isolated from thermal water and surface water by
      electrospray ionization Fourier transform ion cyclotron resonance mass
      spectrometry.
AB  - Characterization of humic substances isolated from thermal water and surface
      water was carried out by elemental analysis and electrospray ionization Fourier
      transform ion cyclotron resonance mass spectrometry. Atomic ratios derived from
      elemental analysis represented compositional differences of humic substances.
      Hydrogen-to-carbon and oxygen-to-carbon atomic ratios were also calculated from
      molecular formulae determined by ultra high-resolution mass spectrometry. The van
      Krevelen diagram was used to illustrate the bias between the atomic ratios from
      elemental analysis and mass spectrometry.

PMID- 20814083
TI  - Ion trajectory simulations in a high-pressure cylindrical ion trap.
AB  - We present the simulation of a cylindrical ion trap (CIT) at high pressure (5-25
      Torr range). SIMION 7.0 software was used for the simulations. The effect of
      pressure, RF frequency and trap dimensions has been investigated. The shape of
      stability diagrams at non-zero pressure is drastically different from the one
      observed in vacuum. Preliminary experimental results are shown, using a r = z = 3
      mm-long CIT at 12 Torr for trapping peptide and protein ions.

PMID- 20814084
TI  - Unexpected formation of complexes between protonated organic ligand and neutral
      salt molecule studied by electrospray ionization mass spectrometry.
AB  - Protonated organic ligands containing pyridine moieties form complexes with
      undissociated salt molecules present in solution, especially with ZnCl(2), as
      proved by electrospray ionization mass spectrometry. In the gas phase, the ions
      observed, for example [L1H + ZnCl(2)](+), lose an HCl molecule producing ions [L1
      + ZnCl](+) (L1 = 1,1,3,3-Tetramethyl-1,3-bis(3-(3-(2
      pyridyl)propoxy)propyl)disiloxane). The use of other zinc salts (for example
      ZnI(2)), also yielded the complexes of between protonated ligands and neutral
      salt molecules (for example, [L1H + ZnI(2)](+)), but losses of respective acid
      molecules (for example, HI), proceeded with higher efficiencies than the loss of
      HCl molecule. An increase in solvent polarity, namely the use of water instead of
      methanol, led to the substantial lowering of [L1H + ZnCl(2)](+) ion abundances,
      since fewer undissociated species (for example, ZnCl(2)) were present in the
      solution. Ligand L2 (1,3,5,7-tetramethyl-1,3,5,7-tetrakis(3-(3-(2-
      pyridyl)propoxy)propyl)cyclotetrasiloxane, larger than L1), forms doubly charged
      ions containing one and two ZnCl(2) molecules, for example [L1H(2) +
      ZnCl(2)](+2).

PMID- 20814085
TI  - Structural characterisation of degradation products formed upon di-n-butyl
      phthalate radiolysis by high-performance liquid chromatography electrospray
      tandem mass spectrometry.
AB  - Structural characterisation of 15 degradation products, formed upon di-n-butyl
      phthalate (DBP) radiolysis, has been achieved using a high-performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS/MS) coupling. The dissociation
      behaviour of protonated DBP was first established to be further used to
      characterise structural deviation in the degradation products. Based on accurate
      mass measurements, compounds shown by HPLC-MS analysis were all found to be DBP
      oxidation products, amongst which various sets of isomers could be distinguished.
      Collision-induced dissociation experiments performed on each electrosprayed
      molecule first allowed unambiguous definition of the location of the additional
      oxygen atoms; that is, in the alkyl branch or on the aromatic ring. Although
      location of the oxygen atom in the alkyl branches could not always be precisely
      determined, relative abundances of some product ions allowed oxygenated functions
      to be identified.

PMID- 20814086
TI  - Comparison of electron capture-atmospheric pressure chemical ionization and
      electrospray ionization for the analysis of gambogic acid and its main
      circulating metabolite in dog plasma.
AB  - Gambogic acid (GA), a promising anticancer candidate, is a polyprenylated
      xanthone abundant in the resin of Garcinia morella and Garcinia hanburyi.
      Electron capture-atmospheric pressure chemical ionization (EC- APCI) and
      electrospray ionization (ESI) techniques, both in the negative ion mode, were
      evaluated regarding ionization, fragmentation patterns and sensitivity for
      simultaneous liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis
      of GA and its main circulating metabolite, 10-hydroxygambogic acid (10-OHGA) in
      dog plasma. Both analytes underwent extensive in-source fragmentation in EC-APCI,
      which was not desirable for reliable quantification of these analytes, whereas
      the substitution of ESI for EC-APCI almost eliminated the source instability of
      both analytes. Negative ion ESI was, therefore, chosen for the development of an
      LC-MS/MS method for simultaneous determination of these analytes. After protein
      precipitation by acetonitrile, all analytes were separated on a Luna C18 HST
      column (50 x 2.0 mm i.d., 2.5 microm) with a mobile phase of 20 mmol L(-1)
      ammonium acetate water solution containing 0.2% acetic acid:acetonitrile (18:82,
      v/v). The detection was performed on a tandem mass spectrometer using selective
      reaction monitoring mode. Calibration curves were linear over the range of 10
      6000 ng mL(-1) for GA and 3-2000 ng mL(-1) for 10-OHGA. The method was
      successfully applied to the pharmacokinetics study of GA injection in six beagle
      dogs.

PMID- 20814087
TI  - Serum pattern profiling for analyzing different types of stress by protein chip
      technology: a preliminary study.
AB  - ProteinChip is a widely accepted tool for exploring serum pattern profile to
      evaluate the risk of somatic diseases from different stressors. In this study, by
      using surface-enhanced laser desorption/ionization time-of-flight mass
      spectrometry (SELDI-ToF), the serum proteome from mice under restraint and
      thermal stresses were profiled in detail and compared with the control group.
      Around 150 characteristic peaks were detected in all three groups, with m/z
      ranging from 1500 to 50,000, with most peaks being within the 2000 m/z to 20,000
      m/z range. Compared with the control group, three significant protein peaks with
      m/z values of 2780, 3303 and 3450 appeared specifically in the restrained stress
      group and four other peaks with m/z values of 7500, 7811, 29,950 and 38,565 in
      the thermal stress group. Unexpectedly, no universal positive stress peaks were
      detected. These preliminary results clearly suggested that there might not be a
      common mechanism shared by various psychophysiological disorders under different
      stressors. By fast serum proteomics profiling, SELDI-ToF may be a convenient tool
      for evaluating the risk of stress-induced illness.

PMID- 20814089
TI  - Adhesion of fibroblasts on micro- and nanostructured surfaces prepared by
      chemical vapor deposition and pulsed laser treatment.
AB  - The development of micro- and nanostructured surfaces which improve the cell
      substrate interaction is of great interest in today's implant applications. In
      this regard, Al/Al2O3 bi-phasic nanowires were synthesized by chemical vapor
      deposition of the molecular precursor (tBuOAlH2)2. Heat treatment of such bi
      phasic nanowires with short laser pulses leads to micro- and nanostructured Al2O3
      surfaces. Such surfaces were characterized by scanning electron microscopy (SEM),
      electron dispersive spectroscopy and x-ray photoelectron spectroscopy. Following
      the detailed material characterization, the prepared surfaces were tested for
      their cell compatibility using normal human dermal fibroblasts. While the cells
      cultivated on Al/Al2O3 bi-phasic nanowires showed an unusual morphology, cells
      cultivated on nanowires treated with one and two laser pulses exhibited
      morphologies similar to those observed on the control substrate. The highest cell
      density was observed on surfaces treated with one laser pulse. The interaction of
      the cells with the nano- and microstructures was investigated by SEM analysis in
      detail. Laser treatment of Al/Al2O3 bi-phasic nanowires is a fast and easy method
      to fabricate nano- and microstructured Al2O3-surfaces for studying cell-surface
      interactions. It is our goal to develop a biocompatible Al2O3-surface which could
      be used as a coating material for medical implants exhibiting a cell selective
      response because of its specific physical landscape and especially because it
      promotes the adhesion of osteoblasts while minimizing the adhesion of
      fibroblasts.

PMID- 20814088
TI  - Laser-based direct-write techniques for cell printing.
AB  - Fabrication of cellular constructs with spatial control of cell location (+/-5
      microm) is essential to the advancement of a wide range of applications including
      tissue engineering, stem cell and cancer research. Precise cell placement,
      especially of multiple cell types in co- or multi-cultures and in three
      dimensions, can enable research possibilities otherwise impossible, such as the
      cell-by-cell assembly of complex cellular constructs. Laser-based direct writing,
      a printing technique first utilized in electronics applications, has been adapted
      to transfer living cells and other biological materials (e.g., enzymes, proteins
      and bioceramics). Many different cell types have been printed using laser-based
      direct writing, and this technique offers significant improvements when compared
      to conventional cell patterning techniques. The predominance of work to date has
      not been in application of the technique, but rather focused on demonstrating the
      ability of direct writing to pattern living cells, in a spatially precise manner,
      while maintaining cellular viability. This paper reviews laser-based additive
      direct-write techniques for cell printing, and the various cell types
      successfully laser direct-written that have applications in tissue engineering,
      stem cell and cancer research are highlighted. A particular focus is paid to
      process dynamics modeling and process-induced cell injury during laser-based cell
      direct writing.

PMID- 20814090
TI  - Redetermination of Na(3)TaF(8).
AB  - The crystal structure of trisodium octafluoridotantalate, Na(3)TaF(8), has been
      redetermined using diffractometer data collected at 153 K, resulting in more
      accurate bond distances and angles than obtained from a previous structure
      determination based on film data. The structure is built from layers running
      along [101], which are formed by distorted [TaF(8)] antiprisms and [NaF(6)]
      rectangular bipyramids sharing edges and corners. The individual layers are
      separated by eight-coordinated Na ions. Two atoms in the asymmetric unit are in
      special positions: the Ta atom is on a twofold axis in Wyckoff position 4e and
      one of the Na ions lies on an inversion centre in Wyckoff site 4d.

PMID- 20814091
TI  - Redetermination of iron dialuminide, FeAl(2).
AB  - The crystal structure of iron dialuminide [Corby & Black (1973). Acta Cryst. B29,
      2669-2677] has been redetermined on a single crystal synthesized from the
      elements by arc melting. The compound crystallizes in the triclinic space group P
      1 with 19 atoms per unit cell, one Fe site being on an inversion centre. The
      crystal structure can be described as an inclusion-plus-deformation derivative of
      the orthorhombic YPd(2)Si structure type.

PMID- 20814092
TI  - Poly[[aqua(mu(7)-ethylenediaminetetraacetato)dicadmium(II)] monohydrate].
AB  - The title compound, {[Cd(2)(C(10)H(12)N(2)O(8))(H(2)O)].H(2)O}(n), consists of
      two crystallographically independent Cd(II) cations, one
      ethylenediaminetetraacetate (edta) tetraanion, one coordinated water molecule and
      one solvent water molecule. The coordination of one of the Cd atoms, Cd1, is
      composed of five O atoms and two N atoms from two tetraanionic edta ligands in a
      distorted pentagonal-bipyramidal coordination geometry. The other Cd atom, Cd2,
      is six-coordinated by five carboxylate O atoms from five edta ligands and one
      water molecule in a distorted octahedral geometry. Two neighbouring Cd1 atoms are
      bridged by a pair of carboxylate O atoms to form a centrosymmetric
      [Cd(2)(edta)(2)](4-) unit located on the inversion centre, which is further
      extended into a two-dimensional layered structure through Cd2-O bonds. There are
      hydrogen bonds between the coordinated water molecules and carboxylate O atoms
      within the layer. The solvent water molecules occupy the space between the layers
      and interact with the host layers through O-H...O and C-H...O interactions.

PMID- 20814093
TI  - Ferrocene compounds: methyl 1'-aminoferrocene-1-carboxylate.
AB  - The title compund, [Fe(C(5)H(6)N)(C(7)H(7)O(2))], features one strong
      intermolecular hydrogen bond of the type N-H...O=C [N...O = 3.028 (2) A] between
      the amine group and the carbonyl group of a neighbouring molecule, and vice
      versa, to form a centrosymmetric dimer. Furthermore, the carbonyl group acts as a
      double H-atom acceptor in the formation of a second, weaker, hydrogen bond of the
      type C-H...O=C [C...O = 3.283 (2) A] with the methyl group of the ester group of
      a second neighbouring molecule at (x, -y - 1/2, z - 1/2). The methyl group also
      acts as a weak hydrogen-bond donor, symmetry-related to the latter described C
      H...O=C interaction, to a third molecule at (x, -y - 1/2, z + 1/2) to form a two
      dimensional network. The cyclopentadienyl rings of the ferrocene unit are
      parallel to each other within 0.33 (3) degrees and show an almost eclipsed 1,1'
      conformation, with a relative twist angle of 9.32 (12) degrees . The ester group
      is twisted slightly [11.33 (8) degrees ] relative to the cylopentadienyl plane
      due to the above-mentioned intermolecular hydrogen bonds of the carbonyl group.
      The N atom shows pyramidal coordination geometry, with the sum of the X-N-Y
      angles being 340 (3) degrees .

PMID- 20814094
TI  - Coordination polymers and hydrogen-bonded assemblies of 2,2'-[2,5
      bis(carboxymethoxy)-1,4-phenylene]diacetic acid with ammonium, lanthanum and zinc
      cations.
AB  - We report the synthesis of the 2,2'-[2,5-bis(carboxymethoxy)-1,4
      phenylene]diacetic acid (TALH(4)) ligand and the structures of its adducts with
      ammonium, namely diammonium 2,2'-[2,5-bis(carboxymethyl)-1,4
      phenylenedioxy]diacetate, 2NH(4)(+).C(14)H(12)O(10)(2-), (I), lanthanum, namely
      poly[[aquabis[mu(4)-2,2'-(2-carboxylatomethyl-5-carboxymethyl-1,4
      phenylenedioxy)diacetato]dilanthanum(III)] monohydrate],
      {[La(2)(C(14)H(11)O(10))(2)(H(2)O)].H(2)O}(n), (II), and zinc cations, namely
      poly[[{mu(4)-2,2'-[2,5-bis(carboxymethyl)-1,4-phenylenedioxy]diacetato}zinc(II)]
      trihydrate], {[Zn(C(14)H(12)O(10))].3H(2)O}(n), (III), and poly[[diaqua(mu(2)
      4,4'-bipyridyl){mu(4)-2,2'-[2,5-bis(carboxymethyl)-1,4
      phenylenedioxy]diacetato}dizinc(II)] dihydrate],
      {[Zn(2)(C(14)H(10)O(10))(C(10)H(8)N(2))(H(2)O)(2)].2H(2)O}(n), (IV), the
      formation of all four being associated with deprotonation of TALH(4). Adduct (I)
      is a diammonium salt of TALH(2)(2-), with the ions located on centres of
      crystallographic inversion. Its crystal structure reveals a three-dimensional
      hydrogen-bonded assembly of the component species. Reaction of TALH(4) with
      lanthanum trinitrate hexahydrate yielded a two-dimensional double-layer
      coordination polymer, (II), in which the La(III) cations are nine-coordinate.
      With zinc dinitrate hexahydrate, TALH(4) forms 1:1 two-dimensional coordination
      polymers, in which every Zn(II) cation is linked to four neighbouring TALH(2)(2-)
      anions and each unit of the organic ligand is coordinated to four different
      tetrahedral Zn(II) cation connectors. The crystal structure of this compound
      accommodates molecules of disordered water at the interface between adjacent
      polymeric layers to give (III), and it has been determined with low precision.
      Another polymer assembly, (IV), was obtained when zinc dinitrate hexahydrate was
      reacted with TALH(4) in the presence of an additional 4,4'-bipyridyl ligand. In
      the crystal structure of (IV), the bipyridyl and TAL(4-) entities are located on
      two different inversion centres. The ternary coordination polymers form layered
      arrays with corrugated surfaces, with the Zn(II) cation connectors revealing a
      tetrahedral coordination environment. The two-dimensional polymers in (II)-(IV)
      are interconnected with each other by hydrogen bonds involving the metal
      coordinated and noncoordinated molecules of water. TALH(4) is doubly
      deprotonated, TALH(2)(2-), in (I) and (III), triply deprotonated, viz. TALH(3-),
      in (II), and quadruply deprotonated, viz. TAL(4-), in (IV). This report provides
      the first structural characterization of TALH(4) (in deprotonated form) and its
      various supramolecular adducts. It also confirms the potential utility of this
      tetraacid ligand in the formulation of coordination polymers with metal cations.

PMID- 20814095
TI  - Poly[bis(mu-benzene-1,4-dicarboxylato)bis[mu-6-(4-pyridyl)-5H-imidazolo[4,5
      f][1,10]phenanthroline]dilead(II)]: an interpenetrating alpha-Po net.
AB  - The asymmetric unit of the title compound,
      [Pb(2)(C(8)H(4)O(4))(2)(C(18)H(11)N(5))(2)](n), contains two Pb(II) atoms, two
      benzene-1,4-dicarboxylate (1,4-bdc) dianions and two 6-(4-pyridyl)-5H
      imidazolo[4,5-f][1,10]phenanthroline (L) ligands. Each Pb(II) atom is eight
      coordinated by three N atoms from two different L ligands and five carboxylate O
      atoms from three different 1,4-bdc dianions. The two 1,4-bdc dianions (1,4-bdc(1)
      and 1,4-bdc(2)) show different coordination modes. Each 1,4-bdc(1) coordinates to
      two Pb(II) atoms in a chelating bis-bidentate mode. Each carboxylate group of the
      1,4-bdc(2) anion connects two Pb(II) atoms in a chelating-bridging tridentate
      mode to form a dinuclear unit. Neighbouring dinuclear units are connected
      together by the aromatic backbone of the 1,4-bdc dianions and the L ligands into
      a three-dimensional six-connected alpha-polonium framework. The most striking
      feature is that two identical three-dimensional single alpha-polonium nets are
      interlocked with each other, thus leading directly to the formation of a twofold
      interpenetrated three-dimensional alpha-polonium architecture. The framework is
      held together in part by strong N-H...O hydrogen bonds between the imidazole NH
      groups of the L ligands and the carboxylate O atoms of 1,4-bdc dianions within
      different alpha-polonium nets.

PMID- 20814096
TI  - A mixed-valence chair-like tetranuclear copper(I,II) cluster with three linking
      modes of the 3,5-bis(2-pyridyl)-1,2,4-triazole ligand.
AB  - In the tetranuclear copper complex tetrakis[mu-3,5-bis(2-pyridyl)-1,2,4
      triazolido]bis[3,5-bis(2-pyridyl)-1,2,4-triazolido]dicopper(I)dicopper(II)
      dihydrate, [Cu(I)(2)Cu(II)(2)(C(12)H(8)N(5))(6)].2H(2)O, the asymmetric unit is
      composed of one Cu(I) center, one Cu(II) center, three anionic 3,5-bis(2-pyridyl)
      1,2,4-triazole (2-BPT) ligands and one solvent water molecule. The Cu(I) and
      Cu(II) centers exhibit [Cu(I)N(4)] tetrahedral and [Cu(II)N(6)] octahedral
      coordination environments, respectively. The three independent 2-BPT ligands
      adopt different chelating modes, which link the copper centers to generate a
      chair-like tetranuclear metallomacrocycle with metal-metal distances of about 4.4
      x 6.2 A disposed about a crystallographic inversion center. Furthermore, strong
      pi-pi stacking interactions and O-H...N hydrogen-bonding systems link the
      tetracopper clusters into a two-dimensional supramolecular network.

PMID- 20814097
TI  - [Cr(8)(PhCO(2))(16)O(4)].4CH(3)CN.2H(2)O: structural origin of magnetic
      anisotropy in a molecular spin cluster.
AB  - The Cr(4)O(4) hetero-cubane-centered octachromium(III) cluster
      [Cr(8)(PhCO(2))(16)O(4)] crystallizes from fluorobenzene-acetonitrile as dodeca
      mu(2)-benzoato-tetrabenzoatotetra-mu(4)-oxido-octachromium(III) acetonitrile
      tetrasolvate dihydrate, [Cr(8)(C(7)H(5)O(2))(16)O(4)].4C(2)H(3)N.2H(2)O, (I).
      Crystals produced by this method are significantly more stable than the
      originally published dichloromethane pentasolvate,
      [Cr(8)(PhCO(2))(16)O(4)].5CH(2)Cl(2) [Atkinson et al. (1999). Chem. Commun. pp.
      285-286], leading to a significantly higher quality structure and allowing the
      production of large quantities of high-quality nondeuterated and deuterated
      material suitable for inelastic neutron scattering (INS) measurements. Compound
      (I) reveals a higher symmetry structure in which the cluster sits on a twofold
      rotation axis, and is based on an asymmetric unit containing four
      crystallographically independent Cr positions, two oxide ligands, eight benzoate
      ligands, two acetonitrile solvent molecules and one disordered water molecule.
      All the Cr atoms are six-coordinate, with an octahedral geometry for the inner
      cubane and a more highly distorted coordination environment in the outer
      positions. Despite the higher symmetry, the coordination geometries observed in
      (I) are largely similar to the dichloromethane pentasolvate structure, indicating
      that crystal-packing effects have little influence on the molecular structure of
      [Cr(8)(PhCO(2))(16)O(4)]. Close structural analysis reveals that the high
      magnetic anisotropy observed in the INS measurements is a consequence of the
      distorted coordination geometry of the four outer Cr atoms.

PMID- 20814098
TI  - Two cobalt(III) mono-dimethylglyoximates isolated from one reaction.
AB  - The reaction of cobalt(II) nitrate hexahydrate with dimethylglyoxime (DMGH(2))
      and 1,10-phenanthroline (phen) in a 1:1:2 molar ratio results in two Co(III) mono
      dimethylglyoximates having two chelating phen ligands in cis positions and the
      Co(III) atom coordinated by six N atoms in a distorted octahedral coordination
      geometry. The isolated products differ in the deprotonation state of the DMGH(2)
      ligand. In [mu-hydrogen bis(N,N'-dioxidobutane-2,3-diimine)]tetrakis(1,10
      phenanthroline)cobalt(III) trinitrate ethanol disolvate 1.87-hydrate,
      [Co(2)(C(4)H(6)N(2)O(2))(C(4)H(7)N(2)O(2))(C(12)H(8)N(2))(4)](NO(3))(3).2C(2)H(6)
      .1.87H(2)O, (I), the C(2)-symmetric cation is formed with the coordination
      [Co(DMG)(phen)(2)](+) cations aggregating via a very strong O(-)...H(+)...O(-)
      hydrogen bond with an O...O distance of 2.409 (4) A. Crystals of (I) exhibit
      extensive disorder of the solvent molecules, the nitrate anions and one of the
      phen ligands. Compound (I) is a kinetic product, not isolated previously from
      similar systems, that transforms slowly into (N-hydroxy-N'-oxidobutane-2,3
      diimine)bis(1,10-phenanthroline)cobalt(III) dinitrate ethanol monosolvate 0.4
      hydrate, [Co(C(4)H(7)N(2)O(2))(C(12)H(8)N(2))(2)](NO(3))(2).C(2)H(6)O.0.40H(2)O,
      (II), with the DMGH(-) ligand hydrogen bonded to one of the nitrate anions. In
      (II), the solvent molecules and one of the nitrate anions are disordered.

PMID- 20814099
TI  - Hexaaquanickel(II) disulfato(1,4,8,11-tetraazacyclotetradecane)nickelate(II)
      dihydrate.
AB  - The title compound, [Ni(H(2)O)(6)][Ni(SO(4))(2)(C(10)H(24)N(4))].2H(2)O, is an
      unusual compound in that it is composed of a hexaaqua complex, formally a
      dication, and a mixed-donor complex (four N and two O atoms), formally a dianion,
      with substantial charge separation between the two nickel centres (6.536 A). The
      homoleptic dication complex consists of the weaker-field ligands, whilst the
      dianion retains the coordination of all the higher-field donors. Both nickel ions
      are located at centres of symmetry. This rare compound is placed in the context
      of previously reported structures which emphasizes its peculiarity.

PMID- 20814100
TI  - Poly[diaquabis(mu(3)-hexamethylenetetramine)[mu(2)-2,2'-(piperazine-1,4
      diyl)bis(ethanesulfonato)]disilver(I)]: a three-dimensional pillared-layer
      framework encapsulating a water chain of (H(2)O)(12) clusters.
AB  - The title compound,
      {[Ag(2)(C(8)H(16)N(2)O(6)S(2))(C(6)H(12)N(4))(2)(H(2)O)(2)].12H(2)O}(n), consists
      of a two-dimensional Ag(I)-hexamethylenetetramine (6,3) net pillared by the 2,2'
      (piperazine-1,4-diyl)bis(ethanesulfonate) ligand, which lies across a centre of
      inversion. This compound can also be viewed as a (3,4)-connected topology by
      considering the hexamethylenetetramine ligand and the Ag(I) ion as the three- and
      four-connected nodes, respectively. There is a one-dimensional channel along the
      a axis accommodating a water chain assembled by the (H(2)O)(12) clusters.

PMID- 20814101
TI  - A three-dimensional heterometallic Cu(I)/V(IV) 1,2-bis(1,2,4-triazol-4-yl)ethane
      framework: a new insight into the structure of vanadium oxyfluoride coordination
      hybrids.
AB  - The bitopic ligand 1,2-bis(1,2,4-triazol-4-yl)ethane (tr(2)eth) provides an
      unprecedented short-distance N(1):N(2)-triazole bridging of Cu(I) and V(IV) ions
      in poly[bis[mu(4)-1,2-bis(1,2,4-triazol-4-yl)ethane]di-mu(2)-fluorido
      tetrafluoridodi-mu(2)-oxido-dicopper(I)divanadium(IV)],
      [Cu(2)V(2)F(6)O(2)(C(6)H(8)N(6))(2)](n). The Cu(I) ions and tr(2)eth linkers
      afford a two-dimensional square-grid topology involving centrosymmetric (tr)Cu(mu
      tr)(2)Cu(tr) [tr is triazole; Cu-N = 1.9525 (16)-2.0768 (18) A] binuclear net
      nodes, which are expanded in a third dimension by centrosymmetric
      [V(2)O(2)F(6)](2-) pillars. The concerted mu-tr and mu-O bridging between the
      Cu(I) and V(IV) ions allows a multi-centre accommodation of the vanadium
      oxyfluoride moiety on a cationic Cu/tr(2)eth matrix [Cu-O = 2.1979 (15) A and V-N
      = 2.1929 (17) A]. The distorted octahedral coordination of [VONF(4)] is completed
      by two terminal and two bridging F(-) ions [V-F = 1.8874 (14)-1.8928 (13) and
      2.0017 (13)-2.1192 (12) A, respectively]. The resulting three-dimensional
      framework has a primitive cubic net topology and adopts a threefold
      interpenetration.

PMID- 20814102
TI  - Green chemistry synthesis: 2-amino-3-[(E)-(2-pyridyl)methylideneamino]but-2
      enedinitrile monohydrate and 5-cyano-2-(2-pyridyl)-1-(2-pyridylmethyl)-1H
      imidazole-4-carboxamide.
AB  - The title compounds, C(10)H(9)N(5)O.H(2)O (L1.H(2)O) and C(16)H(12)N(6)O (L2),
      were synthesized by solvent-free aldol condensation at room temperature. L1,
      prepared by grinding picolinaldehyde with 2,3-diamino-3-isocyanoacrylonitrile in
      a 1:1 molar ratio, crystallized as a monohydrate. L2 was prepared by grinding
      picolinaldehyde with 2,3-diamino-3-isocyanoacrylonitrile in a 2:1 molar ratio. By
      varying the conditions of crystallization it was possible to obtain two
      polymorphs, viz. L2-I and L2-II; both crystallized in the monoclinic space group
      P2(1)/c. They differ in the orientation of one pyridine ring with respect to the
      plane of the imidazole ring. In L2-I, this ring is oriented towards and above the
      imidazole ring, while in L2-II it is rotated away from and below the imidazole
      ring. In all three molecules, there is a short intramolecular N-H...N contact
      inherent to the planarity of the systems. In L1.H(2)O, this involves an amino H
      atom and the C=N N atom, while in L2 it involves an amino H atom and an imidazole
      N atom. In the crystal structure of L1.H(2)O, there are N-H...O and O-H...O
      intermolecular hydrogen bonds which link the molecules to form two-dimensional
      networks which stack along [001]. These networks are further linked via
      intermolecular N-H...N(cyano) hydrogen bonds to form an extended three
      dimensional network. In the crystal structure of L2-I, symmetry-related molecules
      are linked via N-H...N hydrogen bonds, leading to the formation of dimers centred
      about inversion centres. These dimers are further linked via N-H...O hydrogen
      bonds involving the amide group, also centred about inversion centres, to form a
      one-dimensional arrangement propagating in [100]. In the crystal structure of L2
      II, the presence of intermolecular N-H...O hydrogen bonds involving the amide
      group results in the formation of dimers centred about inversion centres. These
      are linked via N-H...N hydrogen bonds involving the second amide H atom and the
      cyano N atom, to form two-dimensional networks in the bc plane. In L2-I and L2
      II, C-H...pi and pi-pi interactions are also present.

PMID- 20814103
TI  - Supramolecular interactions in the 2,6-bis(benzimidazol-2-yl)pyridine
      terephthalic acid-water (2/1/4) cocrystal.
AB  - In the title compound, 2C(19)H(13)N(5).C(8)H(6)O(4).4H(2)O, the terephthalic acid
      molecule lies on a crystallographic inversion centre and the H atoms of one water
      molecule exhibit disorder. The maximum deviation of any atom from the mean plane
      through the C and N atoms of the 2,6-bis(benzimidazol-2-yl)pyridine molecule is
      only 0.161 (4) A. In the crystal structure, the water molecules play an important
      role in linking the other molecules via hydrogen bonding. The structure forms a
      three-dimensional framework via strong intermolecular hydrogen bonding. In
      addition, there are pi-pi stacking interactions between the imidazole, pyridine
      and benzene rings.

PMID- 20814105
TI  - Dimeric supramolecular motifs of two carboxylate-guanidinium compounds.
AB  - The structures of N-benzyl-N'-{6-[(4-carboxylatobenzyl)aminocarbonyl]-2
      pyridylmethyl}guanidinium, C(23)H(23)N(5)O(3), (I), and N-[2
      (benzylaminocarbonyl)ethyl]-N'-{6-[(4-carboxylatobenzyl)aminocarbonyl]-2
      pyridylmethyl}guanidinium monohydrate, C(26)H(28)N(6)O(4).H(2)O, (II), both form
      three-dimensional supramolecular hydrogen-bonded networks based on a dimeric
      primary synthon involving carboxylate-guanidinium linkages. The differences in
      the geometries and hydrogen-bonding connectivities are driven by the additional
      methylpropionamide group and water of crystallization of (II).

PMID- 20814104
TI  - Halogen, hydrogen and electrostatic interactions in 2-amino-5-chloro-1,3
      benzoxazol-3-ium nitrate and 2-amino-5-chloro-1,3-benzoxazol-3-ium perchlorate.
AB  - In the title compounds, C(7)H(6)ClN(2)O(+).NO(3)(-) and
      C(7)H(6)ClN(2)O(+).ClO(4)(-), the ions are connected by N-H...O hydrogen bonds
      and halogen interactions. Additionally, in the first compound, co-operative pi-pi
      stacking and halogen...pi interactions are observed. The energies of the observed
      interactions range from a value typical for very weak interactions (1.80 kJ mol(
      1)) to one typical for mildly strong interactions (53.01 kJ mol(-1)). The iminium
      cations exist in an equilibrium form intermediate between exo- and endocyclic.
      This study provides structural insights relevant to the biochemical activity of 2
      amino-5-chloro-1,3-benzoxazole compounds.

PMID- 20814106
TI  - Monothioindigo, determined by microcrystal structure analysis.
AB  - Indigo and thioindigo pigments are used for a wide range of applications. The
      crystal structure of the mixed compound monothioindigo [systematic name: (E)-2-(3
      oxo-2,3-dihydro-1-benzothiophen-2-ylidene)-2,3-dihydro-1H-indol-3-one],
      C(16)H(9)NO(2)S, has been determined by microcrystal structure analysis from a
      crystal with a size of just 1 x 2 x 10 microm. The crystal structure of
      monothioindigo resembles those of indigo and thioindigo. The molecules show
      orientational disorder, with site-occupation factors of 0.962 (2) and 0.038 (2)
      for the major and minor disorder components, respectively. The indigo fragment
      donates an intermolecular hydrogen bond, leading to a criss-cross arrangement of
      molecules similar to that in indigo, whereas the thioindigo fragment exhibits
      only van der Waals interactions and molecular stacking, similar to that in
      thioindigo.

PMID- 20814107
TI  - A monohydrate pseudopolymorph of 3,4-dihydroxybenzophenone and the role of water
      in the crystal assembly of benzophenones.
AB  - During a polymorphism screening of hydroxybenzophenone derivatives, a monohydrate
      pseudopolymorph of (3,4-dihydroxyphenyl)(phenyl)methanone, C(13)H(10)O(3).H(2)O,
      (I), was obtained. Structural relationships and the role of water in crystal
      assembly were established on the basis of the known anhydrous form [Cox,
      Kechagias & Kelly (2008). Acta Cryst. B64, 206-216]. The crystal packing of (I)
      is stabilized by classical intermolecular O-H...O hydrogen bonds, generating a
      three-dimensional network.

PMID- 20814108
TI  - S-(4-Nitrophenyl) 4-nitrobenzenethiosulfonate.
AB  - The title compound, C(12)H(8)N(2)O(6)S(2), (I), is a positional isomer of S-(2
      nitrophenyl) 2-nitrobenzenethiosulfonate [Glidewell, Low & Wardell (2000). Acta
      Cryst. B56, 893-905], (II). The most obvious difference between the two isomers
      is the rotation of the nitro groups with respect to the planes of the adjacent
      aryl rings. In (I), the nitro groups are only slightly rotated out of the plane
      of the adjacent aryl ring [2.4 (6) and 6.7 (7) degrees ], while in (II) the nitro
      groups are rotated by between 37 and 52 degrees , in every case associated with S
      S-C-C torsion angles close to 90 degrees . Other important differences between
      the isomers are the C-S-S(O(2))-C torsion angle [78.39 (2) degrees for (I) and
      69.8 (3) degrees for (II) (mean)] and the dihedral angles between the aromatic
      rings [12.3 (3) degrees for (I) and 28.6 (3) degrees for (II) (mean)]. There are
      two types of C-H...O hydrogen bond in the structure [C...O = 3.262 (7) A and C
      H...O = 144 degrees ; C...O = 3.447 (7) A and C-H...O = 166 degrees ] and these
      link the molecules into a two-dimensional framework. The hydrogen-bond-acceptor
      properties differ between the two isomers.

PMID- 20814109
TI  - 10-Benzyl-4-oxo-2,3,4,10-tetrahydropyrimido[4,5-b]quinolin-2-iminium chloride
      sesquihydrate: a polarized electronic structure within a complex hydrogen-bonded
      sheet structure.
AB  - In the title compound, C(18)H(15)N(4)O(+).Cl(-).1.5H(2)O, one water site is fully
      ordered with unit occupancy while the other, which lies close to an inversion
      centre in the space group C2/c, has only 0.5 occupancy. The cation exhibits bond
      fixation in the fused carbocyclic ring and electronic polarization in the
      terminal heterocyclic ring. The components are linked into complex sheets by a
      combination of N-H...O, N-H...Cl, O-H...O, O-H...Cl and C-H...O hydrogen bonds.

PMID- 20814110
TI  - A tetrahydropentaleno[1,6a-a]naphthalen-4(2H)-one of defined relative
      stereochemistry for use towards Agariblazeispirol C.
AB  - Towards the synthesis of the novel natural product Agariblazeispirol C,
      (5aR*,11bR*)-9-methoxy-3,8,11b-trimethyl-5,6,7,11b-tetrahydro-1H-pentaleno[1,6a
      a]naphthalen-4(2H)-one, C(20)H(24)O(2), has been prepared at a key stage of the
      preparative programme. The structure shows the desired stereochemical outcome of
      the central cyclization protocol, viz. a syn-relationship between the aliphatic
      methyl group on the 11b-position and the methylene group on the 5a-position [C-C
      C-C = -34.57 (18) degrees ].

PMID- 20814111
TI  - 2,2,2-Trifluoro-N-(1a,2,7,7a-tetrahydronaphtho[2,3-b]oxiren-3-yl)acetamide by X
      ray powder diffraction.
AB  - The title compound, C(12)H(10)F(3)NO(2), an important precursor in the
      preparation of benzovesamicol analogues for the diagnosis of Alzheimer's disease,
      was prepared by the epoxidation of 5,8-dihydronaphthalen-1-amine using 3
      chloroperoxybenzoic acid. The structure was determined by X-ray powder
      diffraction, multinuclear NMR spectroscopy and FT-IR spectroscopy. A pair of
      molecules form intermolecular N-H...O hydrogen bonds, involving the amino and
      oxirene groups, to produce a dimer.

PMID- 20814112
TI  - Powder X-ray studies of meso-hexamethyl propylene amine oxime (meso-HMPAO) in two
      different phases.
AB  - Two different forms of meso-3,3'-[2,2-dimethylpropane-1,3
      diylbis(azanediyl)]dibutan-2-one dioxime, commonly called meso-hexamethyl
      propylene amine oxime (HMPAO), C(13)H(28)N(4)O(2), designated alpha and beta,
      were isolated by fractional crystallization and their crystal structures were
      determined by powder X-ray diffraction using the direct-space method with the
      parallel tempering algorithm. The alpha form was first crystallized from
      acetonitrile solution, while the beta form was obtained by recrystallization of
      the alpha phase from diethyl ether. The alpha form crystallizes in the triclinic
      system (space group P-1), with one molecule in the asymmetric unit, while the
      crystal of the beta form is monoclinic (space group P2(1)/n), with one molecule
      in the asymmetric unit. In both phases, the molecules have similar conformations
      and RS/EE geometric isomerism. The crystal packing of the two phases is dominated
      by intermolecular hydrogen-bonding interactions between the two O-H oxime groups
      of an individual molecule and the amine N atoms of two different adjacent
      molecules, which lead to segregation of extended poly(meso-HMPAO) one-dimensional
      chains along the c direction. The structures of the two phases are primarily
      different due to the different orientations of the molecules in the chains.

PMID- 20814113
TI  - Methyl beta-D-galactopyranosyl-(1-->4)-beta-D-allopyranoside tetrahydrate.
AB  - The title compound, C(13)H(24)O(11).4H(2)O, (I), crystallized from water, has an
      internal glycosidic linkage conformation having phi' (O5(Gal)-C1(Gal)-O1(Gal)
      C4(All)) = -96.40 (12) degrees and psi' (C1(Gal)-O1(Gal)-C4(All)-C5(All)) = 
      160.93 (10) degrees , where ring-atom numbering conforms to the convention in
      which C1 denotes the anomeric C atom, C5 the ring atom bearing the exocyclic
      hydroxymethyl group, and C6 the exocyclic hydroxymethyl (CH(2)OH) C atom in the
      betaGalp and betaAllp residues. Internal linkage conformations in the crystal
      structures of the structurally related disaccharides methyl beta-lactoside
      [methyl beta-D-galactopyranosyl-(1-->4)-beta-D-glucopyranoside] methanol solvate
      [Stenutz, Shang & Serianni (1999). Acta Cryst. C55, 1719-1721], (II), and methyl
      beta-cellobioside [methyl beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranoside]
      methanol solvate [Ham & Williams (1970). Acta Cryst. B26, 1373-1383], (III), are
      characterized by phi' = -88.4 (2) degrees and psi' = -161.3 (2) degrees , and
      phi' = -91.1 degrees and psi' = -160.7 degrees , respectively. Inter-residue
      hydrogen bonding is observed between O3(Glc) and O5(Gal/Glc) in the crystal
      structures of (II) and (III), suggesting a role in determining their preferred
      linkage conformations. An analogous inter-residue hydrogen bond does not exist in
      (I) due to the axial orientation of O3(All), yet its internal linkage
      conformation is very similar to those of (II) and (III).

PMID- 20814114
TI  - 1,3,4-Triphenyl-7-trifluoromethyl-1H-pyrazolo[3,4-b]quinoline at 293 and 100 K.
AB  - In the structure of the title compound, C(29)H(18)F(3)N(3), belonging to the
      space group P6(5) (or P6(1)), three symmetry-independent molecules are arranged
      in two chains, with two molecules alternating along the 3(2) axes, whereas the
      remaining molecule forms a chain along [0001] due to the 6(5) screw axis. The
      conformation of each of the molecules is stabilized by an intramolecular C-H...N
      hydrogen bond, with C...N distances in the range 2.964 (6)-3.069 (5) A at room
      temperature (293 K) and 2.943 (4)-3.084 (4) A at low temperature (100 K). One
      molecule has its -CF(3) group ordered even at 293 K, which can be explained only
      by considering its involvement in two weak intermolecular C-H...F interactions,
      with C...F distances in the range 3.084 (6)-3.302 (5) A at 293 K and 3.070 (3)
      3.196 (3) A at 100 K, and also a C-F...N interaction, with a C...N distance of
      3.823 (5) A at 293 K and 3.722 (4) A at 100 K. The trifluoromethyl groups in the
      two remaining molecules are disordered at 293 K, whereas at 100 K the continuous
      (dynamic) positional disorder of one of the -CF(3) groups (of the molecule
      forming the chain along [0001]) is totally eliminated while the -CF(3) group
      disorder remains for the third molecule.

PMID- 20814115
TI  - Epidemiology and transmission of hepatitis G virus infection in dialysis
      patients.
AB  - Hepatitis G virus (HGV) or GB-virus type C (GBV-C) is distributed globally and is
      present in the volunteer blood donor population. For epidemiological studies, HGV
      is of interest in hemodialysis patients who are at risk of parenterally
      transmitted infections. The role of HGV in producing illness and hepatic disease
      has yet to be determined. A review of literature was performed in 2009 to
      summarize scientific reports on epidemiology and pathogenesis of the HGV
      infection and its exposure through hemodialysis.

PMID- 20814116
TI  - Chronic kidney disease in older people; disease or dilemma?
AB  - The majority of patients diagnosed with chronic kidney disease (CKD) are elderly
      and CKD is linked with poor cardiovascular, cognitive, and disability outcomes in
      these people. Only a minority of these patients will progress to end stage renal
      disease (ESRD) while the majority will die due to cardiovascular disease. Thus,
      only a small number of these patients with CKD will benefit from specialist
      nephrologist assessment. The priority for the remainder should be cardiovascular
      disease prevention. We have reviewed specific issues relevant to older people to
      determine high-risk groups with CKD that are likely to benefit from a more
      intensive risk reduction intervention and to allow identification of clinically
      relevant renal disease.

PMID- 20814117
TI  - Post-transplantation diabetes mellitus; frequency and related risk factors: a
      single center study.
AB  - Post-transplantation diabetes mellitus (PTDM) is a serious complication after
      organ transplantation, which could lead to cardiovascular morbidity and
      mortality. The rate of PTDM increased in recent years, probably due to new
      immunosuppressive drugs such as Tacrolimus. In this study, we retrospectively
      evaluated the frequency of PTDM and related risk factors in 644 non diabetic
      patients who underwent renal transplantation. Data was analyzed by chi-square and
      Fisher's exact test in SPSS software ver11.5. Among 644 patients PTDM developed
      in 10.2% similar to literature. PTDM was significantly correlated to age (P value
      = 0.000), positive familial history (P= 0.003) and HBV infection (P= 0.046). In
      conclusion, PTDM is not uncommon in Iranian patients and a positive family
      history of diabetes, HBV infection and older age increases the likelihood to
      develop PTDM.

PMID- 20814118
TI  - Malnutrition predicting factors in hemodialysis patients.
AB  - Malnutrition is a predictor of increased mortality in chronic hemodialysis (HD)
      patients. Various factors may contribute to malnutrition in these patients
      including energy and protein intake, inflammation, and comorbidity. To determine
      the importance of these factors in malnutrition of chronic HD patients, we
      studied 112 chronic HD patients in two centers was evaluated with the Dialysis
      Malnutrition Score (DMS) and anthropometric and biochemical indices. Seventy six
      (67.8%) patients were classified as malnourished. According to DMS score, poor
      protein intake (r= -0.34, P< 0.01), comorbidities (r= -0.24, P< 0.05), poor
      energy intake (r= - 0.18, P< 0.005), and inflammation (r= -0.16, P< 0.05) were
      significant predictors of malnutrition in descending order of importance.
      Multiple regression analysis showed that only poor protein intake was the
      explanatory variable of anthropometric measurements decline including body mass
      index, triceps skin fold thick-ness, mid arm circumference, mid arm muscle
      circumference, fat free mass, fat mass, albumin, creatinine and transferrine.
      None of the mentioned factors predicted the decrease of biochemical markers. We
      conclude that the frequency of malnutrition is high in our population and poor
      protein intake is the primary contributing factor for this condition. Therefore,
      providing enough protein may be a simple and effective way in preventing
      malnutrition in these patients.

PMID- 20814120
TI  - Interrupting connection of superficial and deep veins of the upper extremity at
      the elbow for creation of hemodialysis arteriovenous fistulas.
AB  - We hypothesized that interrupting the connection between superficial and deep
      veins of the upper extremity at the elbow for creation of hemodialysis
      arteriovenous fistulas (AVFs), in addition to adequate dilation of the elbow
      veins, will reduce the risk of steal syndrome and venous hypertension. In this
      prospective study over a period of one year, patients who were candidates for
      creation of elbow AVFs based on Doppler ultrasound findings and physical
      examination, were enrolled into the study. For creation of AVFs, based on the
      anatomy of the vessels, side-to-side or end-to-side anastomosis between the
      brachial artery and either cephalic or median antecubital or basilic veins was
      performed. In some cases, Gracz AVF was created. For interrupting the connection
      between superficial and deep veins, the perforating vein was either ligated or
      used for anastomosis. The patients were then followed-up regarding patency rate
      of the AVF and complications. AVFs were created in 50 patients and the duration
      of follow-up varied from one to eight months. About 56% (n = 28) of the patients
      had history of failed AVF or arteriovenous graft and 48% (n = 24) of them had
      history of insertion of a dual-lumen catheter for hemodialysis. Neuromuscular
      problem (n=1) and infection (n=1) were the observed complications. None of the
      patients developed steal syndrome or venous hypertension. At the end of the
      study, 47 AVFs (94%) were patent and adequate. Our study suggests that
      interrupting the connection between the superficial and deep venous systems of
      the upper extremity can reduce the risk of development of steal syndrome and
      venous hypertension despite side-to-side anastomosis. These techniques provided
      acceptable patency rate for elbow AVFs.

PMID- 20814119
TI  - Oxidative stress in hemodialysis patients receiving intravenous iron therapy and
      the role of N-acetylcysteine in preventing oxidative stress.
AB  - To determine the contribution of injectable iron administered to hemodialysis
      (HD) patients in causing oxidative stress and the beneficial effect of N
      acetylcysteine (NAC) in reducing it, we studied in a prospective, double blinded,
      randomized controlled, cross over trial 14 adult HD patients who were randomized
      into two groups; one group received NAC in a dose of 600 mgs twice daily for 10
      days prior to intravenous iron therapy and the other group received placebo. Both
      the groups were subjected to intravenous iron therapy, 100 mg of iron sucrose in
      100 mL of normal saline given over a period of one hour. Blood samples for the
      markers of oxidative stress were taken before and after iron therapy. After the
      allowance of a week of wash out period for the effect of N-acetylcysteine we
      crossed over the patients to the opposite regimen. We measured the lipid
      peroxidation marker, malondiaaldehyde (MDA), to evaluate the oxidative stress and
      total anti-oxidant capacity (TAC) for the antioxidant level in addition to the
      highly sensitive C-reactive protein (HsCRP). Non-invasive assessment of
      endothelial dysfunction was measured by digital plethysmography before and after
      intravenous iron therapy. There was an increase of MDA (21.97 + 3.65% vs 7.06 +
      3.65%) and highly sensitive C-reactive protein (HsCRP) (11.19 + 24.63% vs 13.19 +
      7.7%) after iron administration both in the placebo and the NAC groups. NAC
      reduced the baseline acute systemic generation of oxidative stress when compared
      to placebo, which was statistically significant with MDA (12.76 + 4.4% vs 9.37 +
      4.40%: P = 0.032) but not with HsCRP though there was a declining trend (2.85 +
      22.75 % vs 8.93 + 5.19%: P = 0.112). Pre-treatment with NAC reduced the
      endothelial dysfunction when compared to placebo, but it was not statistically
      significant, except for reflection index (RI). We conclude that in our HD
      patients NAC reduced the oxidative stress before and after the administration of
      intravenous iron therapy in addition to the endothelial dysfunction induced by
      this treatment.

PMID- 20814121
TI  - Hyperhomocysteinemia and cardiovascular risks in hemodialysis patients.
AB  - The risk of premature and progressive occlusive vascular disease is high in
      chronic uremic patients, and it accounts for more than 40% of the mortality in
      dialysis patients. End stage renal failure (ESRF) patients exhibit elevated
      plasma homocystein levels, about four fold as much as those in the controls, and
      it is now considered as a causative factor for increased risk of cardiovascular
      death among these patients. The aim of this study was to evaluate the
      relationship of total plasma homocysteine level and echocardiographic
      abnormalities as a surrogate of cardiac disease outcome in hemodialysis patients.
      123 adult patients on maintenance hemodialysis and having echocardiography done
      during January till November 2006 were enrolled in this cross-sectional study.
      Plasma homocysteine level was directly related to the presence of aortic
      regurgitation r= 0.27 P= 0.009. There were negative correlations between ejection
      fraction (EF), left ventricular systolic dimension (LV.S) (r= - 0.71, P= 0.0001),
      left ventricular diastolic dimension (LV.D) (r= -0.23 p= 0.01) and age (r= -
      0.021 P= 0.02). In conclusion we did not find the paradoxical reverse
      epidemiology in our patients and plasma total homocysteine level was in direct
      correlation with cardiac risk factors such as left ventricular mass index and
      aortic regurgitation.

PMID- 20814122
TI  - Cinacalcet effect on severe hyperparathyroidism.
AB  - To determine the efficacy and safety of cinacalcet, a calcimimetic drug that
      suppress parathyroid hormone (PTH) production, we studied its effect on 20
      patients (13 males) on maintenance hemodialysis (HD), 80% of them have persistent
      high PTH levels (i.e. more than 80 pmol/L), the remaining patients had PTH levels
      more than 60 pmol/L. Five of 20 (25%) patients dropped out from the study (2
      because of severe GIT upset, one showed severe myalgia and arthralgia, one
      patient due to non compliance and one died at home due to cardiac arrest). The
      remaining 15 patients (10 males) had a mean age of 40 +/- 12.86 years and
      dialysis duration of 29.13 +/- 18.27 months. The follow-up period on cinacalcet
      was 4 months with a single daily oral dose started with 30 mg/day and increased
      gradually according to the PTH levels. Nine (60%) patients were on concomitant
      active vitamin D during the study period with a mean dose of 7.33 +/- 3.39
      MUg/week. There was a significant decrease in the serum PTH levels at the end the
      study compared to that at the start (46.4 +/- 4.7 pmol/L versus 93.3 +/- 25.6
      pmol/L, respectively, P< 0.000), and the target PTH level (< 31.6 pmol/L) was
      achieved in 54% of patients. No significant changes in serum Ca and phosphorous
      levels were observed. We conclude that cinacalcet is an effective therapy to
      suppress the serum PTH levels and allows favorable management of the serum
      calcium and phosphorus levels in HD patients. The drug was well tolerated;
      however, GIT discomfort is a significant side effect that may necessitate drug
      withdrawal in some patients.

PMID- 20814123
TI  - Surrogate markers of subtle renal injury in patients with visceral leishmaniasis.
AB  - Sudanese visceral leishmaniasis (VL) is a disease of children that is
      characterized by fever, hepatosplenomegaly, lymphadenopathy, pancytopenia, and
      renal injury. Microalbuminuria (MA) and urinary retinol binding protein (urRBP)
      are useful markers for glomerular and tubular dysfunctions, respectively. We
      report the prevalence of subtle renal injury in 88 parasitologically confirmed VL
      patients in a cross-sectional and hospital-based study. Blood and urine were
      collected before treatment for hematological, biochemical profiles in addition to
      MA and urRBP measurement using competitive solid phase, sandwich enzyme-linked
      immune sorbent assay (ELISA), and immunoturbidometry. All the patients had normal
      serum urea and creatinine levels and no detectable urRBP. However, 40% of the
      patients had MA detected by ELISA, and 42% were reactive with turbidometry. The
      sensitivity, specificity, positive and negative predictive values for MA
      turbidometric technique were calculated as 100%; 96%; 95% and 100%, respectively.
      In conclusion; subtle renal injury in VL is mainly glomerular. Turbidometry for
      MA measurement is a simple, inexpensive, sensitive, and specific technique with
      high predictive values.

PMID- 20814124
TI  - Urinary tract infections in the era of newer immunosuppressant agents: a tertiary
      care center study.
AB  - We studied the incidence and the risk factors predisposing to post
      transplantation urinary tract infection (UTI) and the association with use of
      different immunosuppressive regimens. We performed a retrospective analysis of
      152 recipients of renal transplantation over a period of two years. Seventy one
      (46.71%) patients had culture positive UTI, Escherichia coli (45.1%) being the
      commonest. Thirty four (22.39%) patients had acute rejection and 14.4% of those
      had suffered UTI in the early post transplant period. Immunosuppression included
      induction with various antibodies and maintenance on antirejection medications.
      Trimethoprim-sulphamethoxazole was given as prophylaxis throughout the period.
      The UTI was treated according to microbiological sensitivity. 2.8% died due to
      urosepsis. In our retrospective analysis renal transplant recipients under the
      age of 45, female gender and diabetics suffered more UTI. Combination therapy
      with micro-emulsion form of cyclosporine A, prednisolone and azathioprine
      developed more UTI (P= 0.0418).

PMID- 20814125
TI  - Management of superficial bladder carcinoma: time to rethink the treatment
      strategies in the era of orthotopic neo-bladder.
AB  - The objective of this study was to evaluate the recurrence and progression, on
      long-term follow-up, of patients with superficial bladder cancer managed with
      bladder sparing approach. A total of 48 patients with superficial bladder cancer,
      initially treated with bladder sparing approach between 1990 and 1992, were
      available for long-term follow-up ranging between 10 and 15 years; the remaining
      patients were lost to follow-up. All patients had undergone transurethral
      resection and adjuvant intravesical therapy. Recurrence was treated with
      resection and adjuvant therapy or radical cystectomy in cases of progression. Out
      of 48 study subjects, 11 had T1G1, 23 had T1G2 and 14 had T1G3 tumor. In the T1G1
      group, 45.5% had recurrence. Four had single recurrence managed successfully with
      TURBT and intravesical therapy. One had multiple recurrences and underwent
      radiotherapy after the fifth recurrence. In the T1G2 group, 82.6% had recurrence
      and majority (60.8%) had multiple recurrences. Out of 14 cases with multiple
      recurrences, eight patients ultimately progressed to invasive bladder carcinoma
      and underwent radical cystectomy. Majority of these underwent ileal conduit
      because ileal neobladder could not be created due to severe fibrosis. All 14
      patients with T1G3 had recurrence, of whom three (21.4%) had single recurrence.
      Out of the 11 other patients (78.6%) who had multiple recurrences, nine developed
      invasive bladder carcinoma and underwent radical cystectomy. Orthotopic neo
      bladder could be performed only in one patient and the remaining had ileal
      conduit or Mainz pouch. We conclude that in the era of orthotopic neo-bladder
      offering good quality of life, radical cystectomy should be considered at the
      earliest opportunity in patients with aggressive superficial bladder cancer.

PMID- 20814126
TI  - Glomerular malondialdehyde levels in patients with focal and segmental
      glomerulosclerosis and minimal change disease.
AB  - Minimal change disease (MCD) and focal and segmental glomerulosclerosis (FSGS)
      are often studied together, because both present with heavy proteinuria and the
      nephrotic syndrome. The precise distinction between MCD and FSGS is sometimes
      difficult because of inadequate number of glomeruli for definite diagnosis. Some
      evidence suggests that markers of lipid peroxidation, such as malondialdehyde
      (MDA) is an index of free radical mediated injury and may be involved in the
      pathogenesis of FSGS. In this study, we assessed the immunoreactivity of MDA, the
      end product of lipid peroxidation in glomeruli of patients with idiopathic FSGS,
      MCD as well as normal controls (NC). Our results showed that the immunostaining
      level of MDA was significantly higher in patients with FSGS (mean = 1.5) than in
      either patients with MCD (mean = 0.16) or normal controls (mean = 0.11) with P
      value < 0.001. Glomerular MDA level correlated well with the degree of
      glomerulosclerosis in patients with idiopathic FSGS. Our data demonstrates that
      the glomerular level of MDA is higher in idiopathic FSGS than MCD. We suggest
      that MDA immunostaining can be helpful in differentiating between FSGS and MCD in
      problematic cases and when we do not have enough glomeruli for definite and
      correct diagnosis.

PMID- 20814127
TI  - Are elderly end-stage renal disease patients more susceptible for drug resistant
      organisms in their sputum?
AB  - End stage renal disease (ESRD) patients are at risk for pneumonia in view of
      their impaired immune status. Similar empiric antibiotic regimens are used in
      elderly as well as young ESRD patients with respiratory tract infections. We
      conducted an observational, cross sectional study between June 2007 and June 2008
      in 100 ESRD patients half being > 65 yrs. All patients had positive sputum
      culture and chest X-ray findings of pneumonia Streptococcus pneumoniae was the
      commonest in younger while Klebsiella pneumoniae in > 65 yrs old patients.
      Elderly patients had significant resistance to common antibiotics. Ceftrioxone
      was the most suitable antibiotic in the younger patients while a combination of
      piperacillin with gentamycin was the best choice in the geriatric age group. In
      conclusion, organisms cultured from sputum in ESRD patients with pneumonia were
      different in the ESRD patients of more than and less than 65 years of age as well
      as the drug susceptibility. We should probably redefine the management of
      pneumonia according to the sensitivities in our local populations to better treat
      these patients.

PMID- 20814128
TI  - Fasting Ramadan in chronic kidney disease patients: clinical and biochemical
      effects.
AB  - Fasting of the month of Ramadan is a pillar of Islam. Muslim patients with
      chronic kidney disease (CKD) usually fast this month. To determine the effects of
      fasting on renal function in CKD patients, we prospectively studied 31 (19 males
      and mean age 54 +/- 14.2 years) CKD patients during the month of Ramadan 1426
      Hijra (4th October - 4th November 2005); 14 patients were in stage III CKD, 12
      had stage IV and 5 had stage V. The mean estimated glomerular filtration rate (e
      GFR) was 29 +/- 16.3 mL/min. Diabetes was the main cause of CKD (19 (61%)
      patients), and hypertension was present in 22 (71%) patients. Clinical assessment
      and renal function tests were performed one month prior to fasting then during
      and a month later. Medications were taken in two divided doses at sunset (time of
      breaking the fast) and pre dawn (before starting the fast). All patients fasted
      the whole month of Ramadan with a good tolerance, tendency to weight reduction,
      and lower systolic and diastolic blood pressure. eGFR showed a significant
      improvement during the fast and the month after. The blood sugar was high during
      fasting with an increment in the Hb A1c. There was better lipid profile,
      reduction of the proteinuria and urinary sodium. We conclude that this study
      demonstrates a good tolerance and safety of fasting Ramadan in CKD patients.

PMID- 20814129
TI  - Proteinuria in adult Saudi patients with sickle cell disease is not associated
      with identifiable risk factors.
AB  - Renal involvement in patients with sickle cell disease (SCD) is associated with
      significant morbidity and mortality. Proteinuria is common in patients with SCD
      and is a risk factor for future development of renal failure. We sought to
      identify risk factors, if any, associated with proteinuria in adult Saudi
      patients with SCD. We studied 67 patients with SCD followed-up at the King Khalid
      University Hospital, Riyadh, Saudi Arabia. All patients underwent 24-hour urine
      collection to measure creatinine clearance and to quantify proteinuria. In
      addition, blood was examined for evaluation of hematological and biochemical
      parameters. Clinical information was gathered from review of the patients'
      charts. A urine protein level of more than 0.150 grams/24 hours was considered
      abnormal. Urine protein was correlated with various clinical and laboratory
      parameters. Thirty-one males and 36 females were evaluated. The mean age of the
      cohort was 23.8 (+/- 7.2) years. Twenty-seven patients (40.3%) had proteinuria of
      more than 0.150 grams/24 hours. The study group had a mean hemoglobin level of
      8.5 (+/- 2.8) g/dL and mean fetal hemoglobin (HbF) level of 14.4% (+/- 7.3%).
      Majority of the patients (61) had hemoglobin SS genotype and six patients had S
      beta0 thalassemia. None of the parameters evaluated correlated with proteinuria
      although there was a borderline association with older age and higher systolic
      blood pressure (P = 0.073 and 0.061 respectively). Hydroxyurea use for more than
      a year was not beneficial. In conclusion, our study suggests that proteinuria in
      adult Saudi patients is not associated with any clear identifiable risk factors.

PMID- 20814130
TI  - Methods used to reduce the prevalence of hepatitis C in a dialysis unit.
AB  - In the present study, we report on the follow-up of the epidemiology of hepatitis
      C viremia in our dialysis unit after our previous report, over the period from
      July 1, 2003 to December 31, 2005. The methods to reduce the prevalence of
      hepatitis C viremia in our center included: strict adherence to universal
      infection control precautions, separation of hepatitis C virus (HCV) positive
      patients from the negative patients and using specially designated machines for
      them, and from July 2003, periodic testing of all patients for HCV-RNA. Following
      the application of the above mentioned methods, we have not had, since 31
      December 2005, any case of sero-conversion from HCV-negative to HCV-positive in
      our dialysis unit and the only HCV-positive patients present were those who were
      already positive at entry. The overall prevalence of HCV-RNA positive patients in
      our unit has presently come down to 6.5%. Although isolation and use of
      designated machines for HCV-RNA positive patients is not recommended following
      the latest guidelines of "Kidney Disease: Improving Global Outcomes" (KDIGO,
      2008), the present study supports previous reports that these measures might be
      beneficial, when there is a high prevalence of HCV-RNA positive patients, and in
      units where due to understaffing or other causes, break in infection control
      procedures is likely to occur.

PMID- 20814131
TI  - Disseminated invasive aspergillosis successfully treated with micafungin in a
      renal transplant recipient.
AB  - Earlier experience with micafungin demonstrated a successful outcome in treating
      pulmonary aspergillosis in leukemic patients. We report a case of renal
      transplant recipient (RTR) who developed disseminated invasive aspergillosis. The
      patient was treated with micafungin with complete clinical and radiological
      response.

PMID- 20814132
TI  - Porphyria cutanea tarda in a chronic hemodialysis patient.
AB  - End-stage renal failure and long-term hemodialysis (HD) treatment promote the
      development of genetically conditioned porphyria cutanea tarda (PCT). Iron
      overload is often associated with this disease and is thought to play a role in
      its pathogenesis. We report a case of HD-related PCT, which improved with
      deferoxamine treatment. A 33-year-old woman, with end-stage renal failure on HD
      since 1998, presented with a history of blisters on the face and dorsum of the
      hands, of several months duration. Laboratory analysis showed: hemoglobin 10.4
      g/dL; a moderate hepatic cytolysis; ferritin 1300 MUg/L (Nl: 8-120 MUg/L) and
      negative serology for HIV, HBV and HCV. Porphyrin analyses showed a PCT pattern.
      Skin biopsy findings and direct immunofluorescence were consistent with PCT. The
      patient received deferoxamine (40 mg/kg intravenously every week for 6 weeks)
      which led to dramatic improvement of the symptoms. Several treatments are
      proposed in the management of dialysis-related PCT. This case confirms that
      deferoxamine can induce rapid and prolonged remission.

PMID- 20814133
TI  - Metformin induced severe hypophosphatemia in a patient on hemodialysis.
AB  - A 67-year-old diabetic and hypertensive woman presented to us with very low serum
      phosphate levels (PO4- =1.1 mg/dL) about 40 days after initiation of hemodialysis
      (HD). The phosphate binders were discontinued, because they were thought to be
      the cause of hypophosphatemia. However, the serum phosphate levels continued to
      remain low during subsequent follow-up visits over one month (PO4--- = 0.7 and
      0.6 mg/dL respectively). The patient had been started on metformin hydrochloride
      (850 mg thrice a day) about 18 days after the beginning of HD. The drug was
      stopped immediately (approximately 50 days after it was started) and the serum
      phosphate levels increased progressively, reaching 4.3 mg/dL. During the period
      with hypophosphatemia, the patient suffered from very intense fatigue and
      weakness (she was unable to walk), anorexia, diarrhea and tenesmus. There were no
      features suggestive of rhabdomyolysis, hemolysis, low blood pressure or
      hypoglycemia; she had low white blood cell and platelet counts. The patient was
      in good clinical condition 2-3 days after the discontinuation of metformin and
      she recovered totally 15 days later. This case is presented due to its rarity as
      well as the observation that despite the patient having severe hypophosphatemia,
      she showed only side effects of metformin. Hypophosphatemia caused only intense
      fatigue and no other symptoms.

PMID- 20814134
TI  - Liposarcoma scroti: A rare tumor.
AB  - Malignant extratesticular tumors (EXTT) are rare. Majority of EXTT are benign;
      lipoma being the commonest. Most of the malignant tumors are solid and have
      nonspecific features on ultrasonography (US). Computed tomography (CT) and
      magnetic resonance imaging (MRI) are more helpful. The authors report a rare case
      of liposarcoma of scrotum that was suspected on ultrasonography and computed
      tomography and confirmed on histopathology.

PMID- 20814135
TI  - Plasmacytoma of the kidney.
AB  - Extramedullary plasmacytoma is a rare malignant neoplasm typically arising
      outside the bone marrow of patients who show no clinical evidence of multiple
      myeloma. Kidney is a rare site for plasmacytoma. We present here a case of
      primary renal plasmacytoma confirmed on histopathology of the specimen and immuno
      histochemistry studies. Patient was treated with radical nephrectomy followed by
      radiotherapy. The case is presented due to its rarity.

PMID- 20814136
TI  - Goodpasture's syndrome in children.
AB  - Goodpasture's syndrome is an autoimmune disease that has rarely been described in
      children, and only 21 cases have been reported till now. Here is a case of a 9
      year-old boy who was diagnosed to have Goodpasture's syndrome.

PMID- 20814137
TI  - Frank hematuria as the presentation feature of acute leukemia.
AB  - Muco-cutaneous bleeding is a common presenting feature of acute leukemias.
      Mucosal bleeding usually manifests as gum bleeding and/or epistaxis but may occur
      in any mucosal surface of the body. Hematuria as an isolated or main presenting
      feature of acute leukemia is rare. We describe two cases of acute leukemia, a 19
      year old male with acute lymphoblastic leukemia and a 52 year old male with acute
      myeloid leukemia, both presenting with gross hematuria. There was no demonstrable
      leukemic infiltration of the urinary tract on imaging studies. Hematuria in these
      patients was likely to be due to occult leukemic infiltration of the urinary
      system, aggravated by thrombocytopenia, as it subsided after starting
      chemotherapy. Our cases highlight that hematuria should be remembered as a rare
      presenting feature of acute leukemia.

PMID- 20814138
TI  - Lupus cystitis in an Omani girl.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by
      multiple organs involvement. Bladder involvement (Lupus cystitis) is a rare
      manifestation of SLE, and occurs in association with gastrointestinal
      manifestations. We report a case of lupus interstitial cystitis with bladder
      irritation and bilateral hydroureteronephrosis in an adolescent female who was
      treated with intravenous methylprednisolone pulse therapy followed by oral
      prednisolone and mycofenolate mofetil (MMF). Her symptoms ameliorated, and the
      hydroureteronephrosis improved. She was presented again with systemic flare up of
      the disease together with hydrouretronephrosis, but without bladder irritation
      symptoms. The diagnosis of lupus cystitis was confirmed by radiographic
      abnormalities, cystoscopy and bladder biopsy.

PMID- 20814139
TI  - Effects of cryoanalgesia on post nephrectomy pain in kidney donors.

PMID- 20814140
TI  - Protein-to-creatinine ratio: a valid estimate and alternative to 24 hour
      proteinuria.

PMID- 20814141
TI  - Persistent headache in a child with the nephrotic syndrome.

PMID- 20814142
TI  - Th-17 lymphocytes.

PMID- 20814143
TI  - Posterior reversible encephalopathy syndrome.

PMID- 20814144
TI  - Hypercalcemia with renal failure in a patient with immunoblastic variant of non
      Hodgkins lymphoma of the bone.

PMID- 20814145
TI  - Urinary tract infection in Iraqi children.

PMID- 20814146
TI  - Associations of various histological morphologies of renal involvement in
      hepatitis B infection: analysis of 118 subjects.

PMID- 20814147
TI  - Profile of living related kidney donors: a single center experience.
AB  - The living related donor still represents the unique source for renal
      transplantation in Morocco. Since 1986, 127 living related potential donors have
      been evaluated and 100 patients have been transplanted at the Ibn Rochd UHC in
      Casablanca. We retrospectively studied the potential donors and determined their
      profile and the exclusion criteria. The mean age at the time of donation was 37
      +/- 11 years (range 18-66 years) and 60% of donors were women. The predominant
      sources of donors were sisters, brothers and mothers of recipients in 34%, 31%
      and 24% respectively. Forty three percent of them were married, 20% housewives
      and 17% unemployed. In addition, 37% were illiterate, 45% school graduates, and
      18% university graduates. Donors and recipients were incomplete HLA match in
      72.7%, identical in 19% and different in 8.3%. The cross matching test was
      negative in all cases. The mean plasma creatinine was 0.8 +/- 0.1 mg/dL with mean
      creatinine clearance of 103.16 +/- 18.18 mL/min.

PMID- 20814148
TI  - Ethical disputes in living donor kidney transplantation: what should we do to
      save lives?
AB  - Living donor kidney transplantation has strong opposition and proponents.
      Opponents argue that this would exploit poor and female while proponents discuss
      the high mortality rate of ESRD patients and the low risk of a living donation.
      In this debate, we reviewed disputes in ethical aspects of living donor kidney
      transplantation to reach to a good overview of the current concepts on the issue.

PMID- 20814149
TI  - Prevalence of central vein stenosis following catheterization in patients with
      end-stage renal disease.
AB  - To determine prevalence of central vein stenosis following catheterization with
      double-lumen temporary catheters, we performed color Doppler sonography in 100
      consecutive patients. We detected central vein stenosis in 18 cases; 11 patients
      in subclavian vein (SCV), 4 patients in internal jugular vein (IJV) and SCV, 2
      patients in SCV and brachiocephalic vein, and 2 patients in IJV stenosis. There
      were statistical difference between groups with and without stenosis regarding
      time from discontinuation of catheters and use of aspirin (ASA). We could not
      find any statistical difference between these two groups regarding age, sex,
      duration of having chronic kidney disease (CKD), and duration of catheter
      remaining in place. We also found that there was a high proportion of stenosis in
      patients who still had catheter in their veins (15 from 44 patients, 34%) in
      comparison with patients who had already the catheters removed from their veins
      (3 from 56 patients, 5%). We conclude that stenosis of central veins can result
      from long indwelling time of central catheter used for hemodialysis. Aspirin may
      have a protective role against stenosis.

PMID- 20814150
TI  - Childhood idiopathic steroid resistant nephrotic syndrome in Southwestern
      Nigeria.
AB  - Clinical charts of 23 Nigerian children diagnosed with idiopathic steroid
      resistant nephrotic syndrome (iSRNS) between January 2001 and December 2007 were
      retrospectively reviewed to determine their clinicopathologic characteristics and
      outcome. iSRNS (54.8%) was primary in 19 patients (83%) and secondary in four
      (17%). The mean age at diagnosis was 8.3 +/- 3.5 years (2.1-13 years).
      Histopathology revealed membranoproliferative glomerulonephritis (MPGN) in 43.5%,
      focal and segmental glomerulosclerosis (FSGS) in 39.1% and mesangial
      proliferative glomerulonephritis in 8.7% of the patients while minimal change
      disease (MCD) and membranous nephropathy accounted for 4.35% each. Routine
      treatment protocol comprised pulse intravenous (i.v.) cylophosphamide infusion
      and i.v. dexamethasone lisinopril or spironolactone. Cumulative Complete
      Remission (CR) rate was 57.12%. The overall median time to CR from start of
      steroid sparing agents in 12/21 treated patients was 4.5 weeks. CR was better
      achieved in MPGN than FSGS (P = 0.0186). Five patients had eight relapses with
      the overall median relapse-free duration being four months. Cumulative renal
      survival at 36 months was 41.8%. The median follow-up duration was eight months.
      Our study revealed that there was a high prevalence of iSRNS and preponderance of
      non-MCD lesions, with MPGN and FSGS being the major morphologic lesions. The
      outcome with steroid and cyclophosphamide-based treatment for iSRNS was further
      enhanced with addition of either lisinopril or spironolactone.

PMID- 20814151
TI  - The globalization of JSSX and DMPK and progress in research.

PMID- 20814152
TI  - Molecular mechanisms of biliary excretion of cefditoren and the effects of
      cefditoren on the expression levels of hepatic transporters.
AB  - Cefditoren, a third generation cephalosporin antibiotics, has been used in
      clinics extensively. Previous results have indicated that cefditoren is excreted
      into bile as unchanged form. To investigate whether canalicular membrane
      transporters of hepatocytes were involved in the biliary excretion of cefditoren,
      we examined the hepatobiliary disposition of cefditoren using probenecid,
      novobiocin and verapamil as inhibitors of Mrp2, Bcrp and P-gp respectively in
      perfused rat livers. The values for the hepatic extraction ratio had no
      statistical significance, whereas cumulative biliary excretion rates of
      cefditoren were significantly reduced to 43.8% and 79.5% over 25 min in the
      perfused probenecid and novobiocin rats, respectively. We further investigated
      the effects of cefditoren on the expression of hepatic transporters by RT-PCR and
      Western blot after oral administration of cefditoren one week. The expression
      levels of Mrp2, Bcrp, Oat2 mRNA were markedly increased, while P-gp and Oct1 mRNA
      were decreased. In concordance with RT-PCR results, Mrp2 expression level
      increased by Western blotting. These results indicate that Mrp2 and Bcrp may be
      involved in the biliary excretion of cefditoren. Cefditoren can up-regulate the
      expression levels of Mrp2, Bcrp and Oat2, and down-regulate P-gp and Oct1 mRNA
      expression. These results provide important data for drug-drug interactions.

PMID- 20814153
TI  - Elevated systemic elimination of cimetidine in rats with acute biliary
      obstruction: the role of renal organic cation transporter OCT2.
AB  - Renal tubular secretion of cationic drugs is dominated by two classes of organic
      cation transporters, OCT2/SLC22A2 and MATE1/SLC47A1, localized to the basolateral
      and brush-border membranes of the renal tubular epithelial cells, respectively.
      However, little is known about the expression and function of these transporters
      in acute cholestasis. Systemic clearance of cimetidine was significantly higher
      in rats with bile duct ligation (BDL) for 24 hours than in sham-operated rats,
      with no significant changes in the volume of distribution between the groups. In
      addition, net tubular secretory clearance of cimetidine was significantly higher
      in the BDL rats compared with the sham rats, with no significant changes in the
      glomerular filtration rate. Moreover, the renal tissue-to-plasma concentration
      ratio of cimetidine was elevated in BDL rats, although the renal tissue-to-urine
      clearance ratio of cimetidine was not different between the two groups. The
      expression level of basolateral organic cation transporter rOCT2 protein in the
      kidney cortex was markedly higher in BDL rats than that in the sham rats, but
      that of H+/organic cation antiporter rMATE1 protein in the brush-border membranes
      was not significantly different between the two groups. These results demonstrate
      that the renal tubular secretion of cimetidine was increased by acute
      cholestasis, and this increase was attributable to elevated expression levels of
      rOCT2 but not of rMATE1 in the rat.

PMID- 20814154
TI  - Consideration of reliable concentrations for prediction of change in enzyme
      activity by mechanism-based inactivation using physiologically-based
      pharmacokinetic model simulations.
AB  - Using physiologically-based pharmacokinetic model simulations with the assumption
      that elimination of inactivator is not altered by mechanism-based inactivation
      (MBI) of the target enzyme, we examined at what concentrations the influence of
      MBI could be accurately and simply predicted. The method utilizing maximum
      unbound systemic concentration as the inactivator concentration (method 1) tended
      to overestimate this influence, and accuracy expressed as the ratio of estimated
      and exact fold decrease in enzyme activity ranged from 0.80 to 8.41. In addition,
      when the volume of distribution was large or the absorption rate constant was
      small, method 1 provided relatively precise estimation, with the ratio of nearly
      1. We propose use of two concentrations, the steady-state average unbound liver
      concentration and maximum limit of steady-state average unbound liver
      concentration, to predict the effects of MBI. The accuracy of prediction of MBI
      using these two concentrations ranged from 0.90 to 1.04 and 0.92 to 2.96,
      respectively, and was higher than that with method 1. These two concentrations
      can be obtained early in the drug development process, and estimated results can
      be expected to contribute to determination of the effects of MBI.

PMID- 20814155
TI  - Effects of CYP2C9*3 and CYP2C9*13 on Diclofenac Metabolism and Inhibition-based
      Drug-Drug Interactions.
AB  - Cytochrome P450 2C9 (CYP2C9) is a polymorphic enzyme responsible for the
      metabolism of many important drugs, including diclofenac. CYP2C9*3 and CYP2C9*13
      are the principal variant alleles found in the Chinese population. CYP2C9*3 has
      been reported to reduce the metabolism of diclofenac and alter the extent of drug
      drug interactions (DDIs). The effects of CYP2C9*13 on diclofenac metabolism are
      not well studied, and the influences of CYP2C9*13 on DDIs between diclofenac and
      clinical drugs are still unknown. In this study, CYP2C9.1 (the wildtype enzyme),
      CYP2C9.3 and CYP2C9.13 were expressed in yeast, and their metabolic kinetics for
      diclofenac 4'-hydroxylation were examined. From the in vitro data, we predicted a
      decrease in the ratio of diclofenac oral clearance (the ratio of oral clearance
      in subjects with variant CYP2C9 alleles to that in wildtype subjects (CL(oral)R))
      in subjects carrying CYP2C9*3 or CYP2C9*13 alleles. Furthermore, we investigated
      the effects of these two alleles on diclofenac-drug interactions. The potentials
      of nine clinically used drugs to inhibit diclofenac 4'-hydroxylation catalyzed by
      the alleles were compared. Our results indicated that CYP2C9.3 and CYP2C9.13 can
      alter the CYP-inhibitory potencies of some tested drugs. In particular, CYP2C9.13
      significantly weakened the inhibitory potencies of sulfaphenazole, fluvastatin,
      fluvoxamine and tranylcypromine. These data provide helpful guidelines for co
      administration of diclofenac with other drugs in individuals carrying CYP2C9*3
      and CYP2C9*13 alleles.

PMID- 20814156
TI  - Human erythrocyte nucleoside transporter ENT1 functions at ice-cold temperatures.
AB  - The functionality of human erythrocyte nucleoside transporter ENT1 was examined
      at ice-cold temperatures (ICT; measured temperature, 0.5-0.7 degrees C) using
      rightside-out membrane vesicles (ROVs). The uptake of uridine, an ENT1 substrate,
      showed saturation kinetics and was inhibited by S-(4-nitrobenzyl)-6-thioinosine
      (NBMPR), a specific ENT1 inhibitor, at both 23 degrees C and ICT. [3H]Uridine
      uptake was markedly trans-stimulated by preloading ROVs with unlabeled uridine or
      ribavirin, another ENT1 substrate, and the overshoot phenomenon was observed at
      ICT. Similarly, [3H]ribavirin uptake was markedly trans-stimulated by unlabeled
      ribavirin or uridine at ICT. The trans-stimulated uptake of [3H]uridine at ICT
      was inhibited by ENT1 inhibitors/substrates such as NBMPR, dipyridamole,
      adenosine, and ribavirin in a concentration-dependent manner. The inhibition of
      [3H]uridine uptake by NBMPR and dipyridamole at ICT was also observed in intact
      red blood cells. Like uridine uptake, [3H]D-glucose uptake by ROVs, which is
      mediated by facilitative glucose transporter GLUT1, was trans-stimulated by
      unlabeled D-glucose at ICT, and the overshoot phenomenon was observed. In
      contrast, the ability of ATP-dependent transport of 5-(and-6)-carboxy-2',7'
      dichlorofluorescein via multidrug resistance-associated protein 5 in inside-out
      membrane vesicles disappeared at ICT. These results clearly indicate that human
      erythrocyte transporters such as ENT1 function even at very low temperatures near
      0 degrees C. The significance of these findings in transporter research is
      discussed.

PMID- 20814157
TI  - Kinetics of 6-thioxanthine metabolism by allelic variants of xanthine oxidase.
AB  - Our previous studies show that 10 xanthine oxidase (XO) variants (Arg149Cys,
      Pro555Ser, Arg607Gln, Thr623Ile, Ile703Val Asn909Lys, Thr910Lys, Pro1150Arg,
      His1221Arg, and Cys1318Tyr) exhibit altered activity toward the endogenous
      substrate xanthine. This study investigates whether these variants also exhibit
      altered kinetics for the exogenous substrate 6-thioxanthine (6-TX). To
      investigate the kinetics of wild-type XO and these variants, expression
      constructs were transfected into mammalian COS-7 cells. S-9 fractions containing
      the expressed proteins were used to determine their kinetic parameters, i.e.,
      K(m), V(max), and intrinsic clearance (CL(int)), for the substrate 6-TX.
      Functional characterization of the 10 XO variants revealed that 4 of the variants
      (Arg149Cys, Asn909Lys, Thr910Lys, and Pro1150Arg) were inactive, 2 (Arg607Gln,
      and Cys1318Tyr) had reduced activity (CL(int), 55.5% and 64.7% less than that of
      wild-type XO, respectively). This study provides comprehensive data regarding how
      genetic variation in XO affects its activity toward 6-TX. We found that the in
      vitro activity of 8 of the XO variants toward 6-TX was functionally affected.
      These results suggeste that polymorphism in the gene encoding XO may increase the
      toxicity of thiopurine drugs such as 6-mercaputopurine.

PMID- 20814158
TI  - Prediction of interindividual variability in pharmacokinetics for CYP3A4
      substrates in humans.
AB  - A method for predicting the interindividual variability of human exposure for
      CYP3A4 substrates using Monte Carlo simulation was developed based on relevant
      factors. The coefficient of variation (CV) values for CYP3A4 content in human
      liver microsomes, hepatic blood flow, liver volume and body weight, and the
      unbound blood fraction were collected from the published literature. The parallel
      tube and dispersion models were found to be appropriate mathematical models to
      describe the pharmacokinetics (PK). Simulation results using 33% as the CV for
      CYP3A4 content reflected reported CV values of the area under the curve (AUC) for
      40 CYP3A4 substrates for both intravenous and oral administration. We also
      successfully predicted the clearance of midazolam in Japanese and in European
      American subjects. In all cases, the simulated mean and SD values reflected the
      reported values. Thus, the interindividual variability of the AUC of CYP3A4
      substrates was predictable for both intravenous and oral administration.

PMID- 20814159
TI  - Deconjugation kinetics of glucuronidated phase II flavonoid metabolites by beta
      glucuronidase from neutrophils.
AB  - Flavonoids are inactivated by phase II metabolism and occur in the body as
      glucuronides. Mammalian beta-glucuronidase released from neutrophils at
      inflammatory sites may be able to deconjugate and thus activate flavonoid
      glucuronides. We have studied deconjugation kinetics and pH optimum for four
      sources of beta-glucuronidase (human neutrophil, human recombinant, myeloid PLB
      985 cells, Helix pomatia) with five flavonoid glucuronides (quercetin-3
      glucuronide, quercetin-3'-glucuronide, quercetin-4'-glucuronide, quercetin-7
      glucuronide, 3'-methylquercetin-3-glucuronide), 4-methylumbelliferyl-beta-D
      glucuronide, and para-nitrophenol-glucuronide. All substrate-enzyme combinations
      tested exhibited first order kinetics. The optimum pH for hydrolysis was between
      3.5-5, with appreciable hydrolysis activities up to pH 5.5. At pH 4, the K(m)
      ranged 44-fold from 22 microM for quercetin-4'-glucuronide with Helix pomatia
      beta-glucuronidase, to 981 microM for para-nitrophenol-glucuronide with
      recombinant beta-glucuronidase. V(max) (range: 0.735-24.012 micromol x min(-1) x
      unit(-1) [1 unit is defined as the release of 1 microM 4-methylumbelliferyl-beta
      D-glucuronide per min]) and the reaction rate constants at low substrate
      concentrations (k) (range: 0.002-0.062 min(-1) x (unit/L)(-1) were similar for
      all substrates-enzyme combinations tested. In conclusion, we show that beta
      glucuronidase from four different sources, including human neutrophils, is able
      to deconjugate flavonoid glucuronides and non-flavonoid substrates at fairly
      similar kinetic rates. At inflammatory sites in vivo the pH, neutrophil and
      flavonoid glucuronide concentrations seem favorable for deconjugation. However,
      it remains to be confirmed whether this is actually the case.

PMID- 20814160
TI  - Comparison of cytochrome P450 3A enzymes in cynomolgus monkeys and humans.
AB  - Drug metabolizing activities of cytochromes P450 (P450s, or CYPs) 3A4 and 3A5 in
      liver microsomes from the cynomolgus monkey [Macaca fascicularis (mf)] were
      investigated and compared with those of human P450 3A enzymes. Low activities for
      dealkylation of ethoxyresorufin and pentoxyresorufin were seen in recombinant
      monkey mfCYP3A4 and mfCYP3A5 and in recombinant human CYP3A4 and CYP3A5 expressed
      in bacterial membranes. Hydroxylation activities of mfCYP3A4 and mfCYP3A5 toward
      coumarin, paclitaxel, diclofenac, flurbiprofen, and S-mephenytoin were below
      detectable levels, as was also true for CYP3A4 and CYP3A5. Monkey mfCYP3A5 and
      mfCYP3A4 were highly active in bufuralol 1'-hydroxylation. mfCYP3A5 was efficient
      at dextromethorphan O-demethylation, although human CYP3A5 was unable to catalyze
      this reaction. Apparent bufuralol 1'-hydroxylation and dextromethorphan O
      demethylation activities of monkey liver microsomes were higher than those of
      human liver microsomes, possibly because of contributions of mfCYP3A5 to these
      P450 2D-dependent drug oxidations. mfCYP3A5 and CYP3A5 catalyzed midazolam 1'
      hydroxylation at a low substrate concentration more efficiently than the
      corresponding CYP3A4. mfCYP3A5 had higher testosterone 6beta-hydroxylase activity
      than mfCYP3A4, but the reverse relationship was observed in oxidation of
      nifedipine and hydroxylation of dexamethasone. These results demonstrate that
      monkey P450 3A enzymes have similar substrate selectivity to that of human P450
      3A enzymes, but exhibit wider substrate selectivity toward P450 2D substrates.

PMID- 20814161
TI  - Increased expression of hepatic organic cation transporter 1 and hepatic
      distribution of metformin in high-fat diet-induced obese mice.
AB  - Although the effect of obesity on drug disposition remains an important issue for
      clinicians, little is known about the effects of obesity on organic cation
      transporter 1 (OCT1) expression and activity. Here, we show that hepatic OCT1
      expression was higher in mice fed a high-fat (HF) diet for 19 weeks compared with
      mice fed a control diet. Since HF diet-induced obese mice exhibited elevation of
      plasma proinflammatory cytokines, leptin, and insulin levels, we evaluated the
      effect of leptin, insulin, and tumor necrosis factor-alpha (TNF-alpha) on OCT1
      mRNA expression in HepG2 cells. Both leptin and insulin significantly increased
      OCT1 mRNA expression in HepG2 cells, but TNF-alpha did not. This finding was
      consistent with in vivo results. Using the OCT1 substrate metformin, we further
      measured the extent of hepatic uptake of metformin in obese and lean mice using
      the ratio of hepatic concentration to plasma concentration of metformin at 1 h
      after administration. The hepatic uptake of metformin was significantly higher in
      mice fed a HF diet compared with lean mice. In conclusion, our results suggest,
      at least in part, that obesity might have an effect on the absorption or
      distribution pharmacokinetics of metformin through an increase in hepatic OCT1
      expression.

PMID- 20814162
TI  - Genetic variations in UDP-glucuronosyltransferase 2B7 gene (UGT2B7) in a Korean
      population.
AB  - Glucuronidation by UDP-glucuronosyltransferase 2B7 (UGT2B7) has been identified
      as an important pathway for the elimination of its substrate drugs in humans.
      Alterations in UGT2B7 function or expression may influence individual variations
      in drug responses. In an effort to screen for UGT2B7 single nucleotide
      polymorphisms (SNPs) in Koreans, the UGT2B7 gene was directly sequenced in 50
      normal subjects. A total of 19 genetic variations were found: seven in exons,
      eight in introns, and four in the 5'-untranslated region. The order of the
      frequency distribution of UGT2B7 variations was: -900A>G, -327G>A, -161C>T,
      10539A>G, 10711G>C and 10806T>A (40%); 2099T>A, 2100C>T, 2283A>G and 2316A>G
      (39%); 12029T>A (37%); 10928C>A (33%); 10541G>A (28%); 10897insA (24%); 372A>G
      (13%) and 211G>T (12%), as well as other minor alleles with less than 10%
      frequency. Nineteen variations were used to characterize linkage disequilibrium
      (LD) structures at the UGT2B7 locus. Eight tagging SNPs in UGT2B7 were
      determined. Identification of UGT2B7 SNPs with LD and the tagging SNPs lays the
      foundation for investigating UGT2B7-related genotype/phenotype association
      studies for Koreans as well as other populations.

PMID- 20814163
TI  - Six novel single nucleotide polymorphisms of the steroid sulfatase gene in a
      Japanese population.
AB  - Steroid sulfatase (STS) is a microsomal enzyme responsible for the formation of
      3beta-hydroxysteroid from the corresponding sulfate conjugates. Screening of all
      exons, exon-intron boundaries and the 5'-flanking region of the STS gene in 93
      healthy Japanese individuals was carried out. Among seven single nucleotide
      polymorphisms (SNPs) identified in this study, six were novel, including one in
      the untranslated region of exon 1, one in exon 10, and four in the 5'-flanking
      region. The nonsynonymous SNP (1647G>A) in exon 10 caused amino-acid replacement,
      Val476Met, with a frequency of 0.014. The allele frequencies of the other SNPs
      were 0.071 for 155G>A, 0.007 for -21G>A, 0.014 for -1117T>C, 0.106 for -1588G>A,
      0.007 for -2427G>A and 0.007 for -2837T>C.

PMID- 20814164
TI  - Characteristics and validity of a web-based Kawasaki disease surveillance system
      in Japan.
AB  - BACKGROUND: Although regular nationwide surveys of Kawasaki disease (KD) are
      conducted in Japan, there is no system for detecting the real-time epidemic
      status of this disease. METHODS: A web-based surveillance system for KD was
      developed. After consideration of the number of patients reported by prefecture
      to the 19th nationwide survey, 355 pediatric departments were asked to
      participate in the surveillance, and 225 agreed. Since January 2008,
      pediatricians in these 225 hospitals have reported KD patient data immediately
      after diagnosis. The daily numbers of patients are available to the public via
      the internet at http://www.kawasaki-disease.net/kawasakidata/. The validity of
      the data in 2008 was evaluated using the Japanese 20th nationwide survey of KD as
      the gold standard. RESULTS: A total of 3376 patients were reported to the web
      based surveillance system from the 1st week through 52nd week of 2008. The number
      of patients reported to the nationwide survey during the same period was 11 680:
      a total of 4950 patients from the hospitals participating in the web-based
      surveillance and 6730 from other hospitals. The epidemic curves were similar, and
      the correlation coefficient between the web-based surveillance and the total
      numbers in the nationwide survey was 0.806 (P < 0.01). CONCLUSIONS: The web-based
      surveillance system for Kawasaki disease in Japan demonstrated good validity.

PMID- 20814165
TI  - Ambulance transport of the oldest old in Tokyo: a population-based study.
AB  - BACKGROUND: Few studies have investigated ambulance utilization in people aged 85
      years or older, ie, the oldest old. METHODS: We conducted a 1-year population
      based observational study of patients transported by ambulance to emergency
      departments in Tokyo, Japan, which has a population of about 12 million.
      Demographic data, symptoms/events associated with ambulance transport, and the
      proportion of hospital admissions were recorded. Transport rates by age and sex
      were calculated using data for the background population and ambulance
      transports, and the 10 most frequent symptoms/events requiring transport were
      compared between the oldest old and those aged 65 to 84 years. RESULTS: Of the
      642,764 patients who were transported to hospitals by ambulances, 59 570 (9%)
      were aged >= 85 years; 64% were women. The annual ambulance transport rate for
      this population was 250 per 1000/year and was significantly greater than the rate
      (90 per 1000/year) for those aged 65 to 84 years. The highest rate was for men
      aged 85 to 99 years (292 per 1000/year). Among the oldest old, the most frequent
      reason for ambulance transport was fall (38.5 per 1000/year), and the symptom
      most likely to result in hospital admission was dyspnea. CONCLUSIONS: The
      ambulance transport rate for the oldest old was high, particularly among men aged
      >= 95 years. To reduce the need for ambulance transport among the oldest old,
      preventive care is needed to reduce falls and acute exacerbations of cardiac and
      respiratory disorders.

PMID- 20814166
TI  - Birth weight, maternal body mass index, and early childhood growth: a prospective
      birth cohort study in China.
AB  - BACKGROUND: The relations of birth weight and maternal body mass index (BMI) to
      overweight remain unresolved. We prospectively examined the relations of birth
      weight with various anthropometric measures at age 3 to 6 years, the effect of
      maternal BMI, and the patterns of these relations in an analysis using 9 birth
      weight categories. METHODS: The subjects were 210 172 singleton infants born
      alive with a gestational age >= 28 weeks between October 1993 and December 1996;
      the subjects were followed up in 2000. Birth weight, maternal height and weight,
      and other relevant information were measured or collected prospectively.
      Overweight and underweight were defined by using National Center for Health
      Statistics/World Health Organization reference data. Logistic regression models
      were used to estimate relative risks. Analyses stratified by quartile of maternal
      BMI were performed to examine the effects of maternal BMI on the associations of
      birth weight with overweight and underweight. RESULTS: Birth weight was linearly
      associated with height, weight, and BMI at age 3-6 years. Adjustment for maternal
      BMI did not alter this association. Birth weight was positively associated with
      overweight and negatively associated with underweight. The relation curves for
      both overweight and underweight resembled half of a flat parabolic curve. The
      associations for overweight and underweight were slightly stronger for the
      highest and lowest quartiles of maternal BMI, respectively. CONCLUSIONS: Higher
      birth weight is associated with an increased risk for childhood overweight, and
      lower birth weight with an increased risk for underweight. The associations
      between birth weight and early childhood anthropometric growth measures could not
      explained by maternal BMI.

PMID- 20814167
TI  - Inhibition of the ubiquitin-proteasome system leads to delay of the onset of ZGA
      gene expression.
AB  - In mammalian oocytes, the ubiquitin-proteasome system (UPS) is suggested to play
      important roles in oocyte meiosis resumption, spindle assembly, polar body
      emission and pronuclear formation by regulating cyclin B1 degradation. However,
      little is known about the direct relationship between zygotic gene activation
      (ZGA) and degradation of maternal proteins. Here, we investigated the role of the
      UPS in the onset of ZGA in early mouse embryos. First, we found degradation of
      cyclin B1 protein in fertilized oocytes at 1 hpi by western blot analysis and
      used these oocytes throughout this study. Subsequently, we determined optimal
      experimental conditions for transient inhibition of proteasomal activity by
      specific and reversible proteasomal inhibitor MG132 in the G1 phase of the first
      cell cycle. Under the selected optimal conditions, we subjected transient MG132
      treated embryos to reverse transcription (RT)-PCR analysis of expression of four
      ZGA genes, i.e., the hsp70.1, MuERV-L, eif-1a and zscan4d genes. As a result, we
      found that onset of expression of the four examined ZGA genes was delayed in both
      normally developed 2-cell embryos and arrested 1-cell embryos. Our results
      indicate that proteasomal degradation of proteins by the UPS plays a pivotal role
      in the molecular mechanisms of ZGA in early mouse embryos.

PMID- 20814168
TI  - Time-lapse videomicrographic observations of blastocyst hatching in cattle.
AB  - Morphological changes of cultured bovine blastocysts during hatching were
      observed using time-lapse videomicrography in order to investigate the patterns
      of the hatching process that occurred in the blastocysts and to determine whether
      the hatching patterns differed between blastocysts developed from fresh and
      cryopreserved embryos. Compacted morulae (CMs) were collected from superovulation
      treated Japanese Black and Holstein dairy cattle and cultured in a medium in a
      CO(2) culture chamber equipped with an inverted microscope at 38.5 C. Images of
      resultant blastocysts during the period from blastocoel formation to completion
      of hatching were taken at 4-sec intervals by a CCD color camera connected to an
      inverted microscope and recorded by a time-lapse video cassette recorder. In
      blastocysts developed from fresh CMs, hatching was found to begin with protrusion
      of trophectoderm cells from zonae pellucidae at the expanded stage. Protrusion of
      the cells occurred in any site of the trophectoderm. After protrusion, a large or
      small slit was formed in the zona pellucida in all blastocysts as a result of
      blastocyst expansion or enlargement of the protrusion. Then, blastocysts
      completely escaped from the zona pellucida through the slit in the state of
      expansion. From these findings, the hatching patterns of cattle blastocysts could
      be classified into 5 types. In blastocysts developed from frozen-thawed CMs, the
      hatching pattern and length of time needed for hatching are similar to those in
      blastocysts developed from fresh CMs. In addition, the pregnancy rate of
      recipients following transfer of frozen-thawed CMs (52.4%) did not differ from
      that of recipients following transfer with fresh CMs (58.3%). These results
      suggested that the quality of frozen-thawed cattle embryos is comparable to that
      of fresh embryos and that there could be a relationship between the hatching
      pattern of blastocysts and the viability of embryos after transfer.

PMID- 20814169
TI  - Effect of steroids on HOXA10 mRNA and protein expression and prostaglandin
      production in the porcine endometrium.
AB  - The homeobox A (HOXA) family of genes is responsible for segmental development of
      the female reproductive tract during embryogenesis. However, HOXA10 has been
      shown to be essential not only for uterus development, but also for implantation.
      Persistent expression and steroid-dependent regulation of this gene has been
      demonstrated in adult human, primate, murine and canine uteri. Moreover, HOXA10
      dependent expression of prostaglandin H synthase-2 (PGHS-2), a key enzyme in
      prostaglandin production, has been previously detected. The role of the HOXA10
      gene in the porcine uterus is not well established. Therefore, the present
      studies were undertaken to 1) examine the effect of E(2) and P(4) on HOXA10 mRNA
      and protein content in the endometrium collected on day 9 of the estrous cycle
      and 2) determine the PGHS-2 protein expression and PGE(2) and PGF(2alpha)
      secretion from endometrial tissue in response to steroid treatment. Endometrial
      explants collected from mature gilts on day 9 of the estrous cycle were incubated
      with E(2) (1-100 nM), P(4) (10-1000 nM) or E(2) (10 nM) and P(4) (100 nM) for 24
      h. E(2) alone or E(2) in the presence of P(4) increased HOXA10 mRNA expression in
      the endometrium (P<0.05). The HOXA10 protein level was upregulated in response to
      E(2), P(4) and both steroids administered simultaneously (P<0.05). Moreover, E(2)
      and P(4) stimulated PGHS-2 protein expression in cultured endometrial explants.
      PGE(2), but not PGF(2alpha), secretion increased in the presence of E(2)
      (P<0.05). However, the release of both prostaglandins was decreased after
      treatment of endometrial explants with the highest dose of P(4) (P<0.01). These
      results demonstrate that E(2) and P(4) are important regulators of HOXA10 gene
      expression in the adult porcine endometrium during the mid-luteal phase of the
      estrous cycle. Additionally, the similar profiles of endometrial HOXA10 and PGHS
      2 expression in the presence of E(2) and P(4) indicate that both genes are
      simultaneously regulated by steroids in the porcine uterus.

PMID- 20814170
TI  - Prediction of fetal sex by amplification of fetal DNA present in cow plasma.
AB  - The aim of the present study was to predict fetal sex at different time points of
      gestation in cattle by detecting the fetal SRY gene in cow plasma. Plasma DNA was
      extracted from the blood samples of 110 pregnant cows during the gestational
      period of 30 to 242 days. Nested PCR was employed to detect the fetal SRY, which
      the male fetus carries exclusively, in cow plasma. The cows positive for SRY were
      predicted to carry male fetuses. The results showed that the fetal DNA from cow
      plasma was successfully amplified and that fetuses could be sexed with an overall
      accuracy rate of 100% (43/43) for males and 91.0% (61/67) for females and with
      accuracy rates of 100% (3/3) for males and 85.7% (12/14) for females at 30 EN 59
      days of gestation and 100% (40/40) for males and 92.5% (49/53) for females at
      more than 2 months of gestation, respectively. This suggests that the molecular
      method developed here could be used in sex prediction for fetuses.

PMID- 20814171
TI  - Production of genetically modified porcine blastocysts by somatic cell nuclear
      transfer: preliminary results toward production of xenograft-competent miniature
      pigs.
AB  - Galalpha1-3Gal (alpha-Gal epitope) is the major xenoantigenic epitope responsible
      for hyperacute rejection upon pig-to-human xenotransplantation. Endo-beta
      galactosidase C (EndoGalC) from Clostridium perfringens can digest the alpha-Gal
      epitope. In this study, gene-engineered primary cultured porcine embryonic
      fibroblasts (PEF) expressing EndoGalC were obtained and subjected to somatic cell
      nuclear transfer (SCNT) to test whether xenograft-competent pigs can be created.
      The EndoGalC-expressing PEF clones exhibited highly reduced expression of alpha
      Gal epitope, as revealed by cytochemical staining with BS-I-B(4) isolectin, a
      lectin that specifically binds to alpha-Gal epitope, and FACS analysis. The
      pattern of low level of alpha-Gal epitope expression continued for at least 6
      months (more than 10 generations) after isolation. SCNT of nuclei from these
      cells resulted in the generation of blastocysts that displayed nearly complete
      loss of alpha-Gal epitope from their cell surface. This is the first study to
      demonstrate that SCNT using EndoGalC-expressing PEFs as donors would be useful
      for production of genetically modified cloned pigs suitable for
      xenotransplantation.

PMID- 20814172
TI  - Involvement of DNA-PK and ATM in radiation- and heat-induced DNA damage
      recognition and apoptotic cell death.
AB  - Exposure to ionizing radiation and hyperthermia results in important biological
      consequences, e.g. cell death, chromosomal aberrations, mutations, and DNA strand
      breaks. There is good evidence that the nucleus, specifically cellular DNA, is
      the principal target for radiation-induced cell lethality. DNA double-strand
      breaks (DSBs) are considered to be the most serious type of DNA damage induced by
      ionizing radiation. On the other hand, verifiable mechanisms which can lead to
      heat-induced cell death are damage to the plasma membrane and/or inactivation of
      heat-labile proteins caused by protein denaturation and subsequent aggregation.
      Recently, several reports have suggested that DSBs can be induced after
      hyperthermia because heat-induced phosphorylated histone H2AX (gamma-H2AX) foci
      formation can be observed in several mammalian cell lines. In mammalian cells,
      DSBs are repaired primarily through two distinct and complementary mechanisms:
      non-homologous end joining (NHEJ), and homologous recombination (HR) or homology
      directed repair (HDR). DNA-dependent protein kinase (DNA-PK) and ataxia
      telangiectasia mutated (ATM) are key players in the initiation of DSB repair and
      phosphorylate and/or activate many substrates, including themselves. These
      phosphorylated substrates have important roles in the functioning of cell cycle
      checkpoints and in cell death, as well as in DSB repair. Apoptotic cell death is
      a crucial cell suicide mechanism during development and in the defense of
      homeostasis. If DSBs are unrepaired or misrepaired, apoptosis is a very important
      system which can protect an organism against carcinogenesis. This paper reviews
      recently obtained results and current topics concerning the role of DNA-PK and
      ATM in heat- or radiation-induced apoptotic cell death.

PMID- 20814173
TI  - Effects of Ginkgo biloba extract on promotion of neurogenesis in the hippocampal
      dentate gyrus in C57BL/6 mice.
AB  - Ginkgo biloba leaf extract (Gb) has been known to improve blood flow and preclude
      the tissue from free radical damage. Effects of Gb were examined by using Ki67, a
      specific proliferative marker for cellular proliferation, and doublecortin (DCX),
      a marker for immature neurons, indicating degree of neuroblast differentiation in
      the hippocampal dentate gyrus (DG) of adult C57BL/6 mice. The mice were fed with
      Gb at 40 and 100 mg/kg once daily for 28 days. The increase of Ki67- and DCX
      immunoreactive cells in the DG was increased in a dose-dependent manner.
      Especially, the group having 100 mg/kg Gb showed a significant increase of DCX
      immunoreactive neuroblasts with well-developed tertiary dendrites. Expression of
      DCX protein in the Gb groups was also significantly increased upon compared with
      the vehicle group. The results suggested that repeated intake of Gb would enhance
      cell proliferation and neuroblast differentiation in the mouse DG.

PMID- 20814174
TI  - Social mobility and psychiatric disabilities: an assessment of the social
      causation and social selection hypotheses.
AB  - Social mobility is the movement of individuals, families and groups from one
      social position to another. Researchers indicate that people with psychiatric
      disabilities tend to come from lower socioeconomic status groups, and that the
      causal relationship between lower socioeconomic status and mental illness occurs
      through social mobility process. The purpose of this study was to examine the
      occupational social mobility process of a sample of self-identified
      psychiatrically disabled individuals who have been active members of the labor
      force for most of their adult lives. A total of 200 participants were recruited
      from the customers of a One-Stop Career Center in Gloucester County, New Jersey.
      The social mobility pattern of persons with psychiatric disabilities was compared
      to that of persons without psychiatric disabilities (n = 100 for each group).
      That is, the social selection and the social causation hypotheses were applied to
      the social mobility patterns of people with psychiatric disabilities. It was
      revealed that the social class distribution for fathers of people with
      psychiatric disabilities was not different from that of people without
      psychiatric disabilities and also there was no significant social mobility
      difference between the two groups. These findings do not support the social
      causation and the social selection hypotheses. Specifically, the findings
      demonstrate that occupational capabilities and skills of people with psychiatric
      disabilities have been stabilized and are similar to those of people without
      psychiatric disabilities. Furthermore, these results may dispute several biases
      and prejudices with regard to social mobility process of persons with psychiatric
      disabilities.

PMID- 20814175
TI  - Cryptococcosis in the central nervous system in a 36-year-old Japanese man: an
      autopsy study.
AB  - Cryptococcus neoformans is present in our surroundings, and is particularly
      common in bird feces, such as pigeon droppings. Autopsy cases of cryptoccocal
      meningoencephalitis in young individuals are very rare. The aim of this study is
      to describe the autopsy findings of cryptococcal meningoencephalitis of the brain
      and spinal cord in a young man who presented no apparent immunosuppression. A 36
      year-old Japanese man presented with hemoptysis and admitted to our hospital.
      Chest X-ray revealed a small cavity in the left lung. He soon developed
      somnolence, neck stiffness, positive abnormal neurological reactions, and
      increased muscular tonus. Cryptococcus neoformans was detected in the
      cerebrospinal fluid. Despite appropriate chemotherapy (amphotericin B), he died
      18 days after the admission. Autopsy revealed clouding of the leptomeninges of
      the brain and spinal cord. The brain (1,830 g, normal 1,300-1,500 g) showed
      marked edema and bilateral tonsillar herniation. The lung revealed a cavity in
      the left lower lobe. Microscopically, the leptomeninges were diffusely
      infiltrated with numerous cryptococcus fungi and mononuclear cells. Cryptococcus
      fungi were also present in the parenchyma of the brain and spinal cord, in which
      mild gliosis and vascular proliferation were recognized. The lung cavity revealed
      a presence of Cryptococcus neoformans and gram-positive bacteria with
      granulomatous tissue reactions. The cryptococcal granulomas were also recognized
      in the liver and spleen. The cause of death was thought to be tonsillar
      herniation. The present study indicates that severe cryptococcosis involving
      leptomeninges and parenchyma of the brain and spinal cord may occur in an
      otherwise healthy individual.

PMID- 20814176
TI  - Sunitinib-induced thyrotoxicosis followed by persistent hypothyroidism with
      shrinkage of thyroid volume.
AB  - Sunitinib, a tyrosine kinase inhibitor, has been approved for the treatment of
      cancers, such as advanced renal cell carcinoma (RCC). On the other hand,
      sunitinib treatment is known to induce thyroid dysfunction in a substantial
      proportion of patients treated for advanced RCC; in fact, hypothyroidism is a
      frequent complication. However, little is known about sunitinib-induced
      thyrotoxicosis and destructive thyroiditis. Here, we report a patient with RCC
      who developed transient overt thyrotoxicosis followed by hypothyroidism due to
      sunitinib treatment. A 58-year-old woman, who had been treated with chronic
      thyroiditis, was diagnosed as having left RCC with bone metastasis to the rib.
      The patient underwent resection of the left kidney and the bone metastasis
      lesion. However, 3 months later, bone metastasis to the rib recurred, and
      sunitinib treatment was started. At 6 weeks of sunitinib therapy, the patient
      developed transient thyrotoxicosis, followed by persistent hypothyroidism. In the
      thyrotoxic phase, the patient was diagnosed as having destructive thyroiditis
      based on an increased thyroglobulin level, a low radioactive iodine uptake,
      increased free thyroxine level, and suppressed thyroid-stimulating hormone level.
      The thyroid volume in the hypothyroid phase was 68% of that in the thyrotoxic
      phase. In conclusion, the present report suggests that sunitinib-induced
      persistent hypothyroidism may be a consequence of preceding destructive
      thyroiditis with transient thyrotoxicosis. The decreased volume of the thyroid
      during the hypothyroid phase indicates irreversible organ damage in the present
      patient, thereby resulting in persistent hypothyroidism. Thus, periodic
      surveillance of thyroid function is mandatory during sunitinib therapy.

PMID- 20814177
TI  - Connective tissue growth factor cooperates with fibronectin in enhancing
      attachment and migration of corneal epithelial cells.
AB  - Corneal wound healing is a complex process involving the integrated actions of
      various growth factors, cytokines and extracellular matrix produced by corneal
      cells and inflammatory cells. Connective tissue growth factor (CTGF) has been
      linked to wound healing, and fibronectin (FN) is a major component of the
      extracellular matrix. However, the functions of CTGF and FN in corneal epithelial
      cells are not well understood. We therefore investigated the coordinated function
      of CTGF and FN in the attachment and migration of corneal epithelial cells.
      Treatment of human corneal epithelial cells (HCECs) with transforming growth
      factor (TGF) beta1 up-regulated the expression of CTGF, but did not noticeably
      affect FN expression, as judged by immunoblot analysis of cell lysates. In
      contrast, the amount of FN accumulated in the cultured media was increased in a
      time-dependent manner, but CTGF was undetectable in the cultured media. The
      expression level of FN was decreased by the knockdown of CTGF expression with a
      specific short hairpin RNA, indicating that CTGF acts as an upstream mediator of
      FN expression. CTGF augmented the FN-mediated increase in the attachment of HCEC
      by about twofold, although CTGF alone did not influence the attachment. Moreover,
      the migration assay with rabbit corneal blocks revealed that CTGF (390 nM) alone
      or in combination of FN (10 microg/mL) promoted corneal epithelial migration; the
      mean migration distances of control, CTGF, and CTGF + FN were 272, 325, and 626,
      microm, respectively. In conclusion, CTGF cooperates with FN in enhancing the
      attachment and migration of corneal epithelial cells.

PMID- 20814179
TI  - Establishment of a novel xenograft model for human uterine leiomyoma in
      immunodeficient mice.
AB  - Uterine leiomyomas are the most common gynecological benign tumor and greatly
      affect reproductive health and wellbeing, but the pathophysiology and
      epidemiology of uterine leiomyoma are poorly understood. One of the major reasons
      for the slow progress in leiomyoma research is the lack of a good in vivo model
      system. We therefore aimed to develop a novel model by transplanting human
      uterine leiomyoma xenografts in an immunodeficient mouse strain (NOD/SCID/gammac
      null: NOG). Human uterine leiomyoma tissues were cut into small pieces and
      inserted subcutaneously into the right and left flanks of NOG mice. Estrogen
      supplementation was needed to maintain the features of uterine leiomyoma in
      xenografted tissues. After 4 weeks or 8 weeks of transplantation, xenografted
      tissues were harvested and analyzed regarding tissue morphology, collagen
      content, and proliferation and apoptosis of uterine leiomyoma smooth muscle
      cells. The xenografts that were harvested after 4 weeks and 8 weeks retained the
      histological architecture of original uterine leiomyoma tissue both in cellular
      and collagen components. The expression profiles of key markers of uterine
      leiomyoma were also maintained, including estrogen receptor, progesterone
      receptor, and alpha-smooth muscle actin, as judged by immunohistochemical
      staining. The proportion of proliferating cells was significantly increased (1.5
      fold) in the xenografts after 8 weeks of transplantation, whereas that of the
      apoptotic cells remained unchanged. Importantly, the reproducible results were
      obtained with the tumor tissues derived from six patients. The present in vivo
      model may provide a useful tool for development of novel therapeutic strategies
      for uterine leiomyoma.

PMID- 20814178
TI  - Octreotide, a somatostatin analogue, in the treatment of chylothorax associated
      with idiopathic fibrosing mediastinitis.
AB  - Fibrosing mediastinitis (FM) is a rare benign disorder that is characterized by
      excessive fibrotic reactions in the mediastinum. FM is associated with various
      diseases, including Histoplasma capsulatum infection and IgG4-related disease,
      and may compromise the airways, great vessels, and other mediastinal structures.
      Chylothorax is not a common manifestation of FM, and there is no standard
      treatment for FM or chylothorax. Recently, however, somatostatin and octreotide,
      a somatostatin analogue, were successfully used for the treatment of chylothorax
      due to various causes, and they are considered as putative therapeutic
      interventions for chylothorax. Here, we present a 28-year-old Japanese man with
      chylothorax due to idiopathic FM, who was successfully treated with octreotide.
      The patient visited our hospital because of dyspnea on exertion. On admission,
      chest computed tomography revealed pericardial effusion, bilateral pleural
      effusion, and a mass in the mediastinum. The right pleural effusion appeared
      chylous, with the triglyceride level of 253 mg/dl. The biopsy specimen from the
      mediastinal mass showed collagenous fibers and fibroblasts with moderate
      infiltration of lymphocytes. Neither fungi nor bacteria were cultured from the
      biopsy specimen. Steroid therapy was not effective. The patient was then treated
      with subcutaneous octreotide (100 microg three times daily). Five days after
      starting the treatment, the drained pleural fluid was decreased to approximately
      150 ml/day from approximately 1,000 ml/day. The mediastinal mass decreased in
      size 2 weeks after the initiation of octreotide treatment. After discharge, the
      patient has received octreotide treatment for 6 months without serious adverse
      events. We suggest octreotide as a treatment option for FM.

PMID- 20814180
TI  - Piwi-like 2 mediates fibroblast growth factor signaling during gastrulation of
      zebrafish embryo.
AB  - Piwi (P-element-induced wimpy testis) proteins have been shown to play important
      roles in maintenance of germ line stem cells, germ cell proliferation and
      differentiation, and control of Piwi-interacting RNAs (PiRNAs). PiRNAs comprise a
      broad class of small noncoding RNAs that function as an endogenous defense system
      against transposable elements. Fibroblast growth factor (Fgf) signals, mediated
      partly by no tail gene (ntl), are responsible for patterning embryo and mesoderm
      formation. To understand the function of Piwi proteins, we used zebrafish as a
      model system. In zebrafish, piwi-like 2 gene (piwil2) is also required for germ
      cell differentiation and meiosis. Here we report that piwil2 knockdown is able to
      inhibit the expression of fibroblast growth factor 8a (fgf8a). In contrast,
      injection with piwil2 mRNA enhances fgf8a expression. Knockdown of piwil2 reduces
      the inductive effect of fgf8a on dorsalized phenotype, in which embryos extend to
      an oval shape at the end of epiboly stage. Coinjection with fgf8a and piwil2
      mRNAs led to more seriously dorsalized phenotype than coinjection with fgf8a mRNA
      and piwil2-cMO. In addition, knockdown of piwil2 inhibits the inductive effect of
      fgf8a on ntl, whereas overexpression of piwil2 enhances the inductive effect of
      fgf8a on ntl. We also demonstrate that piwil2 positively regulates ntl expression
      at bud stage, while piwil2 negatively regulates ntl expression at 24 hours post
      fertilization. Thus, the functional consequences of piwil2 expression vary during
      early development of zebrafish embryo. Taken together, we suggest that zebrafish
      piwil2 is a mediator of Fgf signals in gastrula period.

PMID- 20814181
TI  - Emphysematous pyelonephritis: tertiary care center experience in management and
      review of the literature.
AB  - INTRODUCTION: In recent years there have been changes in management modality and
      a lower mortality with conservative management. We analyzed the result of
      emphysematous pyelonephritis (EPN) management by a review of the literature.
      MATERIAL AND METHODS: We made a retrospective study for the period from August
      2005 to July 2009. Patients were evaluated by CT and subclassified based on CT.
      The patients managed in different modalities and their outcomes were compared.
      RESULTS: A total of 28 patients were admitted with the diagnosis of EPN. The age
      range was 22-70 years. Five patients were managed conservatively, 17 patients
      underwent minimally invasive modalities (double J stent, pigtail drainage). Open
      drainage of the abscess was conducted in 2 patients, and 4 patients required
      emergency nephrectomy. Emergency nephrectomy is associated with a high mortality
      (75%). CONCLUSIONS: In the majority of cases, EPN was successfully treated by
      resuscitation and minimally invasive modalities. Percutaneous drainage should be
      part of the initial management strategy. This strategy is associated with a lower
      mortality than emergency nephrectomy.

PMID- 20814183
TI  - Are we making a real difference? Update on 'hidden mortality' in the management
      of congenital diaphragmatic hernia.
AB  - Reports of improved survival rates for cases of congenital diaphragmatic hernia
      (CDH) patients have prevailed in the literature over the past 10 years. These
      improvements have been attributed to advances in medical management in the
      postnatal period. However, further inquiries into the true survival of CDH
      patients through population-based studies have revealed that the reported
      increase in survival outcomes, which are often single institution-based reports,
      are confounded by case selection bias which fails to consider those CDH patients
      who do not reach the referral centers. This apparent discrepancy between
      population-based and institution-based statistics raises the question of 'hidden
      mortality' and the role it plays in both research and clinical medicine. In this
      review we will examine the reported survival outcomes of CDH from both
      institution- and population-based perspectives and explore the presence and
      implications of hidden mortality on research methodology and clinical practice.

PMID- 20814184
TI  - Sexual impairment in women undergoing laparoscopic surgery for genital prolapse:
      a hospital-based cohort study.
AB  - INTRODUCTION: No data regarding sexuality following laparoscopic prolapse surgery
      are available to date. Our hypothesis is that laparoscopic sacropexy does not
      influence sexuality negatively, whereas concomitant (vaginal) surgery negatively
      influences sexuality. METHODS: Participants were 132 patients who underwent
      laparoscopic sacropexy. We compared pre- and postoperative sexual scores by 2
      validated questionnaires. RESULTS: The response rate was 84% (111/132). No change
      in sexual activity was reported after surgery. In the sexually active group
      (56.8%; 63/111) the impairment of sexuality was significantly reduced in all age
      groups independently of concomitant vaginal surgery. In the sexually inactive
      group, only 4.3% (2/48) were inactive because of vaginal symptoms before
      operation. After the operation these patients stayed inactive; however, 1
      reported reasons unrelated to prolapse. CONCLUSIONS: Laparoscopic prolapse
      surgery reduces sexual impairment in sexually active patients. There appears to
      be no benefit for patients who are not sexually active for reasons related to the
      prolapse. Concomitant surgery does not affect sexual activity.

PMID- 20814185
TI  - Associations of progesterone receptor polymorphisms with age at menarche and
      menstrual cycle length.
AB  - BACKGROUND: Age at menarche and menstrual cycle characteristics are indicators of
      endocrine function and may be risk factors for diseases such as reproductive
      cancers. The progesterone receptor gene (PGR) has been identified as a candidate
      gene for age at menarche and menstrual function. METHODS: Women office workers
      ages 19-41 self-reported age at menarche and participated in a prospective study
      of menstrual function and fertility. First-morning urine was used as the DNA
      source. 444 women were genotyped for a functional variant in PGR, rs1042838
      (Val660Leu), and 264 women were also genotyped for 29 other SNPs across the
      extended gene region. RESULTS: Genetic variation across PGR was associated with
      age at menarche using a global score statistic (p = 0.03 among non-Hispanic
      whites). Women carrying two copies of the Val660Leu variant experienced menarche
      1 year later than women carrying one or no copies of the variant (13.6 +/- 0.5
      vs. 12.6 +/- 0.1; p = 0.03). The Val660Leu variant was also associated with
      decreased odds of short menstrual cycles (17-24 days) (OR, 95% CI: 0.54 [0.36,
      0.80]; p = 0.002). CONCLUSION: Genetic variation in PGR was associated with age
      at menarche and menstrual cycle length in this population. Further investigation
      of these associations in a replication dataset is warranted.

PMID- 20814186
TI  - Parameters governing invasive disease propensity of non-M1 serotype group A
      streptococci.
AB  - Group A Streptococcus (GAS) causes rare but life-threatening syndromes of
      necrotizing fasciitis and toxic shock-like syndrome in humans. The GAS serotype
      M1T1 clone has globally disseminated, and mutations in the control of virulence
      regulatory sensor kinase (covRS) operon correlate with severe invasive disease.
      Here, a cohort of non-M1 GAS was screened to determine whether mutation in covRS
      triggers systemic dissemination in divergent M serotypes. A GAS disease model
      defining parameters governing invasive propensity of differing M types is
      proposed. The vast majority of GAS infection is benign. Nonetheless, many
      divergent M types possess limited capacity to cause invasive infection. M1T1 GAS
      readily switch to a covRS mutant form that is neutrophil resistant and frequently
      associated with systemic infection. Whilst non-M1 GAS are shown in this study to
      less frequently accumulate covRS mutations in vivo, such mutants are isolated
      from invasive infections and exhibit neutrophil resistance and enhanced
      virulence. The reduced capacity of non-M1 GAS to switch to the hypervirulent
      covRS mutant form provides an explanation for the comparatively less frequent
      isolation of non-M1 serotypes from invasive human infections.

PMID- 20814187
TI  - Streptococcal inhibitor of complement promotes innate immune resistance
      phenotypes of invasive M1T1 group A Streptococcus.
AB  - Streptococcal inhibitor of complement (SIC) is a highly polymorphic extracellular
      protein and putative virulence factor secreted by M1 and M57 strains of group A
      Streptococcus (GAS). The sic gene is highly upregulated in invasive M1T1 GAS
      isolates following selection of mutations in the covR/S regulatory locus in vivo.
      Previous work has shown that SIC (allelic form 1.01) binds to and inactivates
      complement C5b67 and human cathelicidin LL-37. We examined the contribution of
      SIC to innate immune resistance phenotypes of GAS in the intact organism, using
      (1) targeted deletion of sic in wild-type and animal-passaged (covS mutant) M1T1
      GAS harboring the sic 1.84 allele and (2) heterologous expression of sic in M49
      GAS, which does not possess the sic genein its genome. We find that M1T1 SIC
      production is strongly upregulated upon covS mutation but that the sic gene is
      not required for generation and selection of covS mutants in vivo. SIC 1.84 bound
      both human and murine cathelicidins and was necessary and sufficient to promote
      covS mutant M1T1 GAS resistance to LL-37, growth in human whole blood and
      virulence in a murine model of systemic infection. Finally, the sic knockout
      mutant M1T1 GAS strain was deficient in growth in human serum and intracellular
      macrophage survival. We conclude that SIC contributes to M1T1 GAS immune
      resistance and virulence phenotypes.

PMID- 20814188
TI  - National audit of patient choice in pediatric GH therapy.
AB  - BACKGROUND: To assess free patient choice for pediatric patients commencing
      growth hormone (GH) therapy within the UK and Republic of Ireland. METHODS: A
      semistructured questionnaire was sent to all members of the British Society for
      Paediatric Endocrinology and Diabetes. RESULTS: Of 55 units responding, three do
      not commence patients on GH. The remaining 52 units included 21 from (all)
      historic growth centres, 13 from other tertiary centres, and 18 from district
      general hospitals. 46/52 units (89%) offer free patient choice, involving:
      demonstration of devices (n = 15), instructional DVDs (6), a combination of both
      (20), or other (3). Median (range) time spent choosing the GH device was 60 (25
      150) min. Device demonstration involved: dialling up doses (39 units),
      assembling/dissembling (38), GH reconstitution (33), considering facilities
      provided by manufacturer (25), injecting patient (19), injecting parent (17),
      showing additional material (11), and cost consideration (4). Median (range)
      number of steps shown per unit was 5 (1-8), with correlation between numbers of
      manufacturers/devices and new patients commenced on GH per unit (R = 0.62 and
      0.61, both p < 0.01), but not with time spent showing devices (R = 0.12 and 0.22,
      p > 0.05). CONCLUSION: Most units now offer some form of patient choice for new
      patients commencing GH therapy, although this involves several different methods,
      with larger units offering more manufacturers and more devices.

PMID- 20814189
TI  - Effect of oxandrolone on glucose metabolism in growth hormone-treated girls with
      Turner syndrome.
AB  - BACKGROUND: The weak androgen oxandrolone (Ox) may increase height but may also
      affect glucose metabolism in girls with Turner syndrome (TS). METHODS: In a
      randomized, placebo-controlled, double-blind study, we assessed the effect of Ox
      at a dosage of either 0.06 or 0.03 mg/kg/day on glucose metabolism in 133 growth
      hormone (GH)-treated girls with TS. Patients were treated with GH (1.33
      mg/m(2)/day) from baseline, combined with placebo (Pl) or Ox from the age of 8,
      and estrogens from the age of 12. Oral glucose tolerance tests (OGTT) were
      performed, and HbA1c levels were measured before, during, and after discontinuing
      Ox/Pl therapy. RESULTS: Insulin sensitivity, assessed by the whole-body insulin
      sensitivity index (WBISI) decreased during GH+Ox/Pl (p = 0.003) without
      significant differences between the dosage groups. Values returned to pre
      treatment levels after discontinuing GH+Ox/Pl. On GH+Ox, fasting glucose was less
      frequently impaired (Ox 0.03, p = 0.001; Ox 0.06, p = 0.02) and HbA1c levels
      decreased more (p = 0.03 and p = 0.001, respectively) than on GH+Pl. CONCLUSIONS:
      We conclude that in GH-treated girls with TS, Ox at a dosage of 0.03 or 0.06
      mg/kg/day does not significantly affect insulin sensitivity. Insulin sensitivity
      decreases during GH therapy, to return to a pre-treatment level after
      discontinuing therapy.

PMID- 20814190
TI  - Natural history of idiopathic advanced bone age diagnosed in childhood: pattern
      of growth and puberty.
AB  - BACKGROUND: Significant idiopathic bone age (BA) advancement is defined as BA >2
      SD above the mean chronological age (CA) with no underlying etiology. BA
      advancement due to endocrinopathies is associated with early puberty and
      compromised adult height (AHt), necessitating treatment. The natural history of
      idiopathic BA advancement is not well-established. AIM: to determine the pattern
      of growth and puberty, and validity of AHt prediction in idiopathic BA
      advancement. METHODS: fifty-five prepubertal patients (20 boys aged 6.7 +/- 2.2
      years, 35 girls aged 6.4 +/- 2.0 years) evaluated between 1985 and 2008 were
      found to have idiopathic BA advancement. Assessed during follow-up were: BA,
      height (Ht), weight (Wt), pubertal course and predicted AHt (PAHt). Attained AHt
      was compared to PAHt and to midparental Ht (MPHt). RESULTS: throughout follow-up,
      BA-SDS (SD score) significantly declined (p < 0.001), Ht-SDS significantly
      decreased (p = 0.006) and Wt-SDS did not change. Pubertal onset, duration and
      growth were within the normal range. Attained AHts did not differ significantly
      from MPHts (boys: 172 +/- 6.7 vs. 171 +/- 6.1 cm; girls: 160.5 +/- 6.5 vs. 159.0
      +/- 6.8 cm). PAHts using the 'accelerated' tables of Bayley and Pinneau were
      accurate. CONCLUSION: idiopathic BA advancement differs from BA advancement with
      underlying endocrinopathy in evolution of BA progression (decline in BA-SDS),
      growth pattern, validity of AHt prediction and uncompromised AHt. This indicates
      that it requires minimal clinical monitoring and usually does not mandate
      treatment.

PMID- 20814191
TI  - Time to recurrence after nephrectomy as a predictor of cancer-specific survival
      in localized clear-cell renal cell carcinoma.
AB  - OBJECTIVE: To evaluate the prognostic impact of early recurrence (within 12
      months) after surgery on cancer-specific survival (CSS) of patients with
      localized clear-cell renal cell carcinoma (ccRCC). METHODS: Patients with
      surgically treated localized ccRCC were studied. Using the Kaplan-Meier method,
      we calculated CSS; by univariate and multivariate models we analyzed the
      association of early recurrence with cancer-related mortality. RESULTS: We
      identified 259 patients with pT1-4/NX/0M0 ccRCC treated between February 1981 and
      September 2009; of 66 (25.5%) with disease recurrence, 29 (43.9%) had early
      relapse. Overall, 43 patients (16.6%) died from ccRCC. The 5- and 10-year CSS for
      those without, late and early recurrence was 98.5 and 96.5%, 53 and 39.8%, and 23
      and 23%, respectively (p < 0.0001). In the multivariate Cox model, pT stage (p =
      0.01) and early recurrence (p < 0.0001) independently predicted CSS. CONCLUSIONS:
      Recurrent disease after localized ccRCC confers a poor prognosis, especially if
      detected within 12 months after surgery. Thus, this criterion should be included
      as an independent risk factor for cancer-related mortality.

PMID- 20814192
TI  - Bladder diverticulum robotic surgery: systematic review of case reports.
AB  - INTRODUCTION: We report one case of robot-assisted transperitoneal bladder
      diverticulectomy and perform a systematic review of published experience. PATIENT
      AND METHODS: Our patient was a 64-year-old male with a history of lower urinary
      tract symptoms secondary to benign prostatic enlargement for 6 years with
      recurrent urinary tract infection. Ultrasound and voiding cystourethrogram showed
      a 7-cm diverticulum in the posterior bladder wall. After bibliographic search in
      PubMed/Medline, 17 articles on laparoscopic diverticulectomy and 8 on robotic
      diverticulectomy were selected. RESULTS: Transperitoneal robot-assisted
      diverticulectomy was performed with the Da Vinci 4-arm system (Intuitive Surgical
      Inc., Sunnyvale, Calif., USA) without perioperative complications. Operative time
      was 80 min and blood loss less than 100 ml. Transurethral prostatic resection
      combined with Greenlight laser vaporization was performed in a second step.
      CONCLUSIONS: Robot-assisted bladder diverticulectomy is safe, effective,
      reproducible and minimally invasive. Cost is higher than for laparoscopic surgery
      and access to this technology is limited.

PMID- 20814193
TI  - Debate: PRO Position. People with chronic kidney disease should have a blood
      pressure lower than 130/80 mm Hg.

PMID- 20814194
TI  - Debate: CON Position. People with chronic kidney disease should have a blood
      pressure lower than 130/80 mm Hg.

PMID- 20814197
TI  - Editorial perspective. The low down on down low.

PMID- 20814198
TI  - Sesame oil accelerates kidney healing following gentamicin-induced kidney injury
      in rats.
AB  - BACKGROUND/AIMS: We investigated the therapeutic effect of a single dose of
      sesame oil against gentamicin-induced renal damage in rats. METHODS: Experimental
      rats were subcutaneously injected with gentamicin (100 mg/kg/day for 7 days) to
      induce renal injury. Sesame oil (1, 2 or 4 ml/kg) was given orally 24 h after the
      last dose of gentamicin. Control rats were treated with saline only. Renal
      injury, histopathological examination, histochemical staining, osteopontin
      expression, superoxide anion, nitric oxide, peroxynitrite radical and lipid
      peroxidation were assessed 24 h after sesame oil administration. RESULTS: Serum
      blood urea nitrogen and creatinine as well as renal osteopontin expression,
      superoxide anion, nitric oxide, peroxynitrite radical and lipid peroxidation
      levels were higher in gentamicin-treated rats than in control rats. Sesame oil
      significantly decreased all the tested parameters compared with gentamicin-alone
      rats. Furthermore, histopathological and histochemical staining showed that renal
      tubules had recovered and regenerated in the sesame oil-treated rats. CONCLUSION:
      We hypothesize that a single dose of sesame oil inhibits oxidative stress to
      shorten the recovery period and allow the regeneration of renal tubules after the
      onset of gentamicin-induced renal injury in rats.

PMID- 20814199
TI  - Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone prevents
      albuminuria but not glomerulosclerosis in experimental diabetes.
AB  - BACKGROUNDS/AIMS: Renal inflammation and nephrin downregulation contribute to
      albuminuria in diabetes. We studied, in streptozotocin-induced diabetic rats, the
      effect of rosiglitazone (RSG), a peroxisome proliferator-activated receptor-gamma
      agonist, on renal macrophage infiltration, MCP1, and nephrin expression in
      relation to albuminuria. METHODS: We investigated control and diabetic rats
      treated or untreated with RSG. Animals were sacrificed at 1, 3, and 9 months.
      Renal MCP1 and nephrin expression were studied by immunoblotting, renal
      macrophage infiltration by immunohistochemistry, and albuminuria by ELISA.
      Electron microscopy was used to assess glomerular ultrastructural morphology. In
      vitro experiments were conducted in isolated cultured rat glomeruli. RESULTS:
      Glycaemic control was similar in diabetic rats treated and untreated with RSG,
      and blood pressure was comparable in all groups. RSG prevented diabetes-induced
      albuminuria at 9 months, and renal macrophage infiltration and MCP1 upregulation
      at 3 and 9 months. Diabetes-mediated nephrin downregulation was abolished by RSG.
      Diabetes-induced glomerulosclerosis, glomerular basement membrane thickening, and
      foot process fusion were not affected by RSG. In isolated glomeruli, MCP1
      directly induced nephrin downregulation and this was prevented by RSG. RSG had no
      effect on nephrin expression. CONCLUSION: RSG prevents albuminuria and nephrin
      downregulation in experimental diabetes independently of glycaemic and blood
      pressure control. This effect likely occurs via correction of diabetes-induced
      inflammatory processes.

PMID- 20814201
TI  - Interaction between tumor necrosis factor-alpha gene -308G/A promoter and leptin
      receptor gene Lys656Asn single-nucleotide polymorphisms: effect on serum leptin
      concentrations.
AB  - BACKGROUND AND OBJECTIVE: The aim of our study was to investigate the interaction
      between the tumor necrosis factor-alpha (TNF-alpha) gene -308G/A promoter and the
      leptin receptor (LEPR) gene Lys656Asn polymorphisms and their effects on serum
      leptin levels in obese subjects. DESIGN: A population of 237 obese patients was
      analyzed prospectively. Bipolar electrical bioimpedance, a biochemical analysis
      and serum concentrations of leptin and TNF-alpha were assessed. RESULTS: The
      number of subjects with both mutations was 21 (8.86%). Subjects carrying the
      mutant LEPR genotype had higher concentrations of leptin than those with the wild
      type LEPR genotype only when they also carried the mutant TNF-alpha genotype
      (G308A or A308A) (82.7 +/- 63 vs. 147.6 +/- 89 ng/ml; p < 0.05). In subjects with
      TNF-alpha G308G, multivariate analysis with leptin as a dependent variable
      revealed fat mass as an independent predictor in the model (F = 15.4; p < 0.05),
      with an increase of 4.1 ng/ml (95% CI 2.5-5.6) per kilogram of fat mass. The same
      was seen in subjects with TNF-alpha G308A and A308A genotypes, with an increase
      in leptin levels of 3.56 ng/ml (95% CI 1.8-5.3) per kilogram fat mass.
      CONCLUSION: There is an interaction between TNF-alpha gene G308A promoter and
      LEPR gene Lys656Asn polymorphisms, with higher concentrations of leptin in the
      G308A and A308A genotypes combined with the mutant LEPR genotype.

PMID- 20814200
TI  - Association of cumulatively low or high serum calcium levels with mortality in
      long-term hemodialysis patients.
AB  - BACKGROUND: The outcome-predictability of baseline and instantaneously changing
      serum calcium in hemodialysis patients has been examined. We investigated the
      mortality-predictability of time-averaged calcium values to reflect the
      'cumulative' effect of calcium burden over time. METHODS: We employed a Cox model
      using up-to-5-year (7/2001-6/2006) time-averaged values to examine the mortality
      predictability of cumulative serum calcium levels in 107,200 hemodialysis
      patients prior to the use of calcimimetics, but during the time where other
      calcium-lowering interventions, including lower dialysate calcium, were employed.
      RESULTS: Both low (<9.0 mg/dl) and high (>10.0 mg/dl) calcium levels were
      associated with increased mortality (reference: 9.0 to <9.5 mg/dl). Whereas
      mortality of hypercalcemia was consistent, hypocalcemia mortality was most
      prominent with higher serum phosphorus (>3.5 mg/dl) and PTH levels (>150 pg/ml).
      Higher paricalcitol doses shifted the calcium range associated with the greatest
      survival to the right, i.e. from 9.0 to <9.5 to 9.5 to <10.0 mg/dl. African
      Americans exhibited the highest death hazard ratio of hypocalcemia <8.5 mg/dl,
      being 1.35 (95% CI: 1.22-1.49). Both a rise and drop in serum calcium over 6
      months were associated with increased mortality compared to the stable group.
      CONCLUSIONS: Whereas in hemodialysis patients cumulatively high or low calcium
      levels are associated with higher death risk, subtle but meaningful interactions
      with phosphorus, PTH, paricalcitol dose and race exist.

PMID- 20814202
TI  - Resistance to acidic environments of caries-associated bacteria: Bifidobacterium
      dentium and Bifidobacterium longum.
AB  - Oral Bifidobacteriaceae, Bifidobacterium dentium and Bifidobacterium longum, are
      known to be isolated together with mutans streptococci and lactobacilli from
      caries lesions, suggesting that these Bifidobacteriaceae are caries associated
      and acid resistant. This study aimed to investigate effects of acidification on
      B. dentium and B. longum, and to compare them with those on Streptococcus mutans,
      Streptococcus sanguinis and Lactobacillus paracasei. Effects of acidification,
      growth ability in a complex medium at a pH of 4.0-8.0, cell viability in 2
      morpholinoethanesulfonic acid monohydrate (MES)-KOH buffer at pH 4.0, as well as
      stability of intracellular pH (pH(in)) at an extracellular pH of 3.5-8.0
      estimated using a fluorescent dye, 5(6)-carboxyfluorescein diacetate N
      succinimidyl ester in MES-KOH, 3-(N-morpholino)propanesulfonic acid-KOH or N,N
      bis(2-hydroxyethyl)glycine-KOH buffer, were investigated. B. longum grew as well
      as Streptococcus strains over a wide pH range, whereas B. dentium grew best in
      the narrow pH range around neutral. The cell viability of B. dentium decreased
      significantly after 2 h of acidification at a pH of 4.0, but this was
      significantly less than that of the Streptococcus and Lactobacillus species,
      whereas B. longum maintained almost 100% viability. The pH(in) was close to the
      extracellular pH at pH of 5.5-7.5 in the Bifidobacterium and Streptococcus
      strains, while at a pH of <5.0, the pH(in) was higher than the extracellular pH
      in all the strains, but the pH(in) maintenance ability of Bifidobacterium strains
      was higher than that of the Streptococcus strains. The high survival rate and
      pH(in) maintenance ability of bifidobacteria comparable to that of S. mutans in
      the acidic environment may account for why bifidobacteria exist as stable species
      in acidic caries lesions together with mutans streptococci.

PMID- 20814203
TI  - Preface. Diagnosis and therapy of pancreatic diseases is still a
      gastroenterological challenge.

PMID- 20814204
TI  - Rational therapy of acute pancreatitis.
AB  - Management of acute pancreatitis represents a challenging aspect of everyday
      clinical practice that requires a multimodal and interdisciplinary approach. Mild
      cases of acute pancreatitis are usually self-limiting and treated with fluid
      resuscitation, analgesics, oxygen administration, and antiemetics. In addition to
      this, the role of nutritional support has been established for patients with
      severe acute pancreatitis with more evidence demonstrating its beneficial
      effects. Antibiotic prophylaxis, even though widely studied and often
      administrated, does not seem to have an effect on the development of
      complications and mortality. Patients who develop infected necrosis of the
      pancreatic tissue require surgical assistance. Various techniques of necrosectomy
      and drainage are accepted as promising methods in the management of severe acute
      pancreatitis.

PMID- 20814205
TI  - Role of imaging methods in diagnosis of acute pancreatitis.
AB  - Diagnosis and treatment of acute pancreatitis is a complex interdisciplinary team
      problem. Without knowledge of classification and the current opinion of other
      experts on this disease, the radiologist cannot be an adequate partner in this
      team. Nonetheless, the radiologist has a very important position, primarily
      'thanks to' computed tomography (CT) in diagnosis and fading of the disease and
      the possibilities offered by minimally invasive treatment of early and late
      complications of this disease. A turning point from the viewpoint of diagnosing
      acute pancreatitis was first marked by Balthazar's classification and then
      establishing the CTSI (severity index for the disease based on CT findings),
      proposed by Balthazar as well. Radiologists' increasingly more active approach to
      drainage of acute fluid collections and pseudocysts in patients with acute
      pancreatitis as well as some possibilities for percutaneous treatment of necroses
      has led to a reassessment of surgeons' attitudes. A persistent problem is the
      correct indication and timing of CT scans and the drainage itself. In their
      concise communication, the authors present data from the literature and summarize
      their own experience. They highlight the most common mistakes, especially in the
      indication and timing of individual methods. Finally, they present their views on
      a practical approach to the use of CT and percutaneous drainage in these
      patients.

PMID- 20814206
TI  - Advances in the etiology of chronic pancreatitis.
AB  - In the past, chronic pancreatitis has been regarded as a fairly uniform and
      largely untreatable disorder that most commonly affects patients who both lack
      gainful employment or adequate insurance coverage and have a tendency to smoke
      and drink. Large clinical trials suggest that this perception is not only
      misguided and discriminatory but also not based on facts. We forgot that the
      perception of chronic liver disease was similar before World War II, and just
      like liver cirrhosis the fibrosis and cirrhosis of the pancreas--i.e. chronic
      pancreatitis--is the end result of a range of environmental, inflammatory,
      infectious and genetic disorders. A growing number of these have only recently
      been recognized as a distinct entity and several of which are becoming truly
      treatable. A large proportion of the risk for developing pancreatitis is conveyed
      by genetic risk factors, and we estimate that less than half of those have been
      identified so far. The same holds true for protective factors that can prevent
      pancreatitis, even in the face of excessive alcohol abuse. Various gene mutations
      and polymorphisms appear to determine an individual's susceptibility for
      developing pancreatic disease, for the severity of the disease, and for the
      disease progression. The spectrum of genotype/phenotype associations ranges from
      straightforward autosomal dominant traits with near-complete penetrance, as for
      the most common mutations in the cationic trypsinogen gene (PRSS1), to moderate
      risks factors without mendelian inheritance patterns, as for SPINK1 and CFTR
      mutations, to very subtle risk associations and disease modifiers that can only
      be identified in large cohort studies, as for the chymotrypsin C, calcium-sensing
      receptor and the anionic trypsin (PRSS2) mutations. Only a better understanding
      of the disease mechanisms that underlie these changes will make an individualized
      therapy of pancreatic disorders a realistic option.

PMID- 20814207
TI  - Classification of chronic pancreatitis.
AB  - Chronic pancreatitis (CP), defined as a continuing inflammatory disease of the
      pancreas characterized by irreversible morphological changes which typically
      cause abdominal pain and/or permanent impairment of pancreatic function, has
      proved resistant to categorization. The disease may present clinically either
      with an individual symptom or a combination of symptoms associated with loss of
      pancreatic function. The single most frequent symptom of CP is pain, either in
      the form of intermittent episodes or in a more chronic or persistent pattern. The
      natural history of CP is usually characterized by progression of tissue damage
      and various degrees of exocrine and endocrine pancreatic insufficiency, which
      will become apparent over time. The main reason for the lack of guided strategies
      in the therapeutic management of CP is the absence of a clinically applicable
      classification of CP. In the past, several classifications have certainly
      contributed to a better understanding of the pathogenesis and pathophysiology of
      CP. The meetings in Marseilles (1963 and 1984), Cambridge (1984) and in Rome
      (1985) added a great deal of information to our knowledge of the pathogenesis and
      evolution of CP. More recent work on understanding the temporal course of CP led
      to the Zurich international classification which has been used to define patient
      cohorts in recent studies of patients undergoing surgery for CP. In order to
      combine clinical experience in the field of CP with progress in diagnostic
      methods and new molecular technologies for the assessment of CP, a classification
      of CP based on key clinical aspects is crucial. A new classification should first
      be validated to determine whether it can be applied to the majority of patients
      with CP, and then the value of such a classification needs to be tested in our
      understanding of the natural course in different etiologies (progression, arrest,
      regression) and most importantly, to study the clinical outcome when different
      therapeutic strategies are applied.

PMID- 20814208
TI  - Autoimmune pancreatitis--recent advances.
AB  - Autoimmune pancreatitis (AIP) is recognized as a distinct clinical entity,
      identified as a chronic inflammatory process of the pancreas in which the
      autoimmune mechanism is involved. Clinically and histologically, AIP has two
      subsets: type 1--lymphoplasmatic sclerosing pancreatitis with abundant
      infiltration of the pancreas and other affected organs with immunoglobulin G4
      positive plasma cells, and type 2--duct centric fibrosis, characterized by
      granulocyte epithelial lesions in the pancreas without systemic involvement. In
      the diagnosis of AIP, two diagnostic criterions are used--the HISORt criteria and
      Asian Diagnostic Criteria. In the differential diagnosis, the pancreatic cancer
      must be excluded by endosonographically guided pancreatic biopsy. Typical signs
      of AIP are concomitant disorders in other organs (kidney, liver, biliary tract,
      salivary glands, colon, retroperitoneum, prostate). Novel clinicopathological
      entity was proposed as an 'IgG4-related sclerosing disease' (IgG4-RSC). Extensive
      IgG4-positive plasma cells and T lymphocyte infiltration is a common
      characteristics of this disease. Recently, IgG4-RSC syndrome was extended to a
      new entity, characterized by IgG4 hypergammaglobulinemia and IgG4-positive plasma
      cell infiltration, this being considered an expression of a lymphoproliferative
      disease, 'IgG4-positive multiorgan lymphoproliferative syndrome'. This syndrome
      includes Mikulicz's disease, mediastinal fibrosis, autoimmune hypophysitis, and
      inflammatory pseudotumor--lung, liver, breast. In the therapy of AIP, steroids
      constitute first-choice treatment. High response to the corticosteroid therapy is
      an important diagnostic criterion. In the literature, there are no case-control
      studies that determine if AIP predisposes to pancreatic cancer. Undoubtedly, AIP
      is currently a hot topic in pancreatology.

PMID- 20814209
TI  - Pancreatic exocrine insufficiency: diagnostic evaluation and replacement therapy
      with pancreatic enzymes.
AB  - In chronic pancreatitis over a course of years to decades, pancreatic parenchyma
      is gradually lost and pain is gradually decreasing as signs and symptoms of
      malabsorption appear. Appearance of calcifications is a late sign and in many
      cases coincides with appearance of steatorrhea. Decreasing output of insulin and
      glucagon results in diabetes mellitus, which is characterized by a high risk of
      hypoglycemias ('brittle' diabetes). In most instances, measurement of fecal
      concentration of elastase may be sufficient to diagnose exocrine pancreatic
      insufficiency. Fecal fat analysis is useful to establish malabsorption and to
      monitor pancreatic enzyme replacement therapy. Components essential to the
      optimal management of chronic pancreatitis are control of pain, improvement of
      maldigestion, management of diabetes and of complications like cysts or
      strictures, and alcohol and nicotine abstinence. Patients with pain are evaluated
      for structural abnormalities which can be treated endoscopically or surgically.
      Conservative treatment of pain includes fat-reduced diet, nonnarcotic analgesics,
      alcohol and smoking cessation, and, if not successful, an 8-week trial of high
      dose pancreatic enzymes. Pancreatic enzymes are used for the treatment of
      maldigestion. Digestion of fat is the determining factor in pancreatic
      insufficiency. Treatment success is defined clinically by improved body weight
      and consistency of feces. Modern pancreatin preparations are engineered as acid
      resistant, pH-sensitive microspheres. Using such preparations, most patients will
      reduce their steatorrhea to <15 g fat per day during supplementation of 25,000
      40,000 IU of lipase per meal, but in selected cases larger doses may be needed,
      depending on size of the meal and severity of the disease. Efficacy of enzyme
      replacement therapy is influenced by denaturation of lipase by gastric acid,
      improper timing of enzymes, coexisting small-intestinal mucosal disease, rapid
      intestinal transit and effects of diabetes. This review focuses on
      pathophysiology, diagnosis and treatment of pancreatic steatorrhea.

PMID- 20814210
TI  - Indications for endoscopic or surgical treatment of chronic pancreatitis.
AB  - In patients suffering from chronic pancreatitis, pain as the predominant symptom
      remains a therapeutic challenge which often cannot be tackled conservatively.
      Since pancreatic duct obstruction - frequently within the pancreatic head - is an
      important etiological factor, treatment in these cases aims at decompressing the
      duct either endoscopically or surgically. Endoscopic drainage includes
      sphincterotomy, dilation of strictures, removal of stones, and insertion of a
      stent; it has a success rate of 30-100%. Surgical treatment may be accomplished
      by drainage or resection procedures. Drainage procedures (such as the
      longitudinal opening of the pancreatic duct followed by a pancreaticojejunostomy)
      can be performed with a low rate of postoperative complications (6-30%) and
      mortality (0-2%), and can achieve long-term pain relief in 65-85% of the cases.
      Furthermore, there are a variety of resection procedures such as
      pancreaticoduodenenectomy (Whipple procedure), pylorus-preserving
      pancreaticoduodenenectomy, different types of the duodenum-preserving pancreatic
      head resection (i.e. Beger, Frey, or Buchler procedures), segmentectomy, and V
      shaped excision of the pancreatic duct. However, the surgical procedure of choice
      is controversially discussed. While it has been shown that parenchyma-preserving
      surgery is superior to more extensive resections, it remains unclear which of the
      modifications of the parenchyma-sparing procedures is suited best for which case.
      Recently, two randomized controlled trials have demonstrated that surgical
      treatment is superior to endotherapy in long-term pain reduction, physical health
      score results, and the number of reinterventions. Thus, in patients with chronic
      pancreatitis refractory to conservative medical treatment, surgery rather than
      endotherapy is the standard of care. Parenchyma-preserving resections should
      preferably be performed because they ensure lower morbidity and mortality,
      preserve endocrine function, and improve quality of life.

PMID- 20814211
TI  - Thrombotic complications of pancreatic cancer: classical knowledge revisited.
AB  - This paper is an updated review of a classical clinical subject: the association
      between deep vein thrombosis and pancreatic cancer. Recent epidemiological data
      support the empirical observation of Trousseau that digestive cancer may induce
      deep vein thrombosis. Pancreatic cancer is among the most common malignancies
      associated with thrombosis, due to the fact that cancer may induce the activation
      of the coagulation. There are genetic factors linked to this association. Cancer
      patients carrying the factor V Leiden mutation and the prothrombin 20210A
      mutation have increased risk to develop thrombosis. Reciprocally, it has been
      speculated that deep vein thrombosis or pulmonary embolism could represent a
      warning sign for a latent cancer. The practical question about this association
      is: shall we recommend searching for pancreatic and other cancers in all patients
      with thrombosis? Present data show that the strategy to look for such
      malignancies in patients with thrombosis on a routine base is not cost-effective.
      Oncological screening should be limited to patients at risk to develop cancer.
      Patients with pancreatic cancer, as with other visceral cancers, should be
      submitted to a prophylactic strategy to prevent thrombosis: therapy with low
      molecular-weight heparin for several weeks was beneficial in several trials.

PMID- 20814212
TI  - Pancreatic cancer: epidemiology and risk factors.
AB  - Ductal adenocarcinoma of the pancreas has an incidence of approximately 10 per
      100,000 population per year. This number pertains to Europe, North America and
      parts of South America (Argentina). Men are more often afflicted than women
      (female:male ratio of about 1:1.5, though reports vary). There has been a very
      small but steady increase in the incidence over the last 50 years. Unfortunately,
      numbers for incidence and mortality are still practically identical for this
      cancer. The peak of incidence is between 60 and 80 years of age. In absolute
      numbers, there are 8,000 cases diagnosed annually in Germany, and 33,000 in the
      US. Pancreatic cancer at <40 years of age is extremely rare (2 cases per million
      per year), but among 80-year-olds, the incidence is about 200 new cases per
      100,000 population per year. In men, carcinoma of the pancreas is the fourth most
      common cause of cancer death after lung, prostate and colorectal cancer. In
      women, it is the fifth most common cause of cancer death. Risk factors for
      pancreatic cancer include high-fat diet, smoking, chronic pancreatitis, primary
      sclerosing cholangitis, hereditary pancreatitis, family history of pancreatic
      cancer and diabetes mellitus. In chronic pancreatitis, the risk for pancreatic
      cancer is increased 20-fold, in hereditary pancreatitis it is 60-fold higher than
      in the general population. In a kindred with 2 first-degree relatives with
      pancreatic cancer, the risk for pancreatic cancer for other members of that
      kindred is 7-fold higher.

PMID- 20814213
TI  - Diagnosis of chronic pancreatitis.
AB  - The diagnosis of chronic pancreatitis is based on a typical history with
      recurrent flares of acute inflammation, imaging procedures and some laboratory
      tests. Using imaging procedures (abdominal ultrasound, computed tomography or
      magnetic resonance imaging), a diagnosis can only be made when alterations in
      size (enlargement or atrophy) or shape of the pancreas or changes in
      intrapancreatic structure (dilation, obstruction of ducts), calcifications, or
      changes in peripancreatic organs have occurred. Tests of exocrine pancreatic
      function are not essential for making a diagnosis of chronic pancreatitis.

PMID- 20814214
TI  - Causes and mechanisms in acute pancreatitis.
AB  - Acute pancreatitis (AP) presents clinically with either mild or severe clinical
      course. There are no effective specific drugs for treatment of AP today. Basic
      knowledge about pathophysiological processes is the key for the development of
      novel therapeutic principles. This article provides a review on the
      pathophysiological mechanisms involved in the early phase of AP.

PMID- 20814215
TI  - Effect of procainhydrochloride on phospholipase A2 catalytic activity in sodium
      taurocholate-induced acute experimental pancreatitis in rats.
AB  - BACKGROUND: In human acute pancreatitis (AP) the local anaesthetic
      procainhydrochloride (procain-HCl) is given intravenously for pain treatment.
      Procain has been shown to inhibit catalytic activity of pancreatic (group I)
      phospholipase A2 (PLA2) and non-pancreatic (group II) PLA2. Both enzymes are
      important mediators for the local and systemic inflammatory process in AP. To
      determine the effect of procain, we examined serum and tissue levels of both
      types of PLA2 activity in the experimental rodent taurocholate model of AP.
      METHODS: In 60 rats, severe pancreatitis was induced by taurocholate. Forty rats
      were treated with procain-HCl intravenously at a dosage of 2 mg/kg body weight/h
      either at or 1 h after induction of pancreatitis. Twenty rats served as controls.
      We measured catalytic activities of group I and group II PLA2 in serum and tissue
      samples of lung and pancreas. RESULTS: Serum group II PLA2 catalytic activity was
      significantly reduced 3 and 6 h after AP induction in rats treated with procain
      HCl (p < 0.001) in both treatment groups. In pancreatic and lung tissue, group II
      PLA2 catalytic activity was significantly reduced compared with normal values (p
      < 0.001). CONCLUSION: Procain-HCl given intravenously either at or 1 h after
      induction of necrotizing pancreatitis significantly inhibits group II PLA2
      catalytic activity in serum and tissues.

PMID- 20814216
TI  - Involvement of the basilar artery in diabetes mellitus: an MRI study of brainstem
      infarctions.
AB  - The relationships among diabetes mellitus (DM), brainstem infarctions (BSIs) and
      involvement of the basilar artery (BA) were investigated in 254 patients with
      acute cerebral infarctions detected on magnetic resonance (MR) imaging.
      Radiological findings included lesion topography and size (mm(2)) of BSIs on MR
      images, and the extent of BA stenosis measured by MR angiography. Adjusted
      logistic regression analyses showed that DM (OR 4.018; p = 0.0006) and BA
      stenosis (OR 1.003 per 1 mm; p < 0.0001) had an independent association with the
      incidence of BSIs, but the lesion size of the BSIs was only associated with BA
      stenosis (beta coefficient 0.280; p < 0.0001). Diabetic patients showed
      significantly more frequent isolated pontine infarctions and a lesser degree of
      BA stenosis (p < 0.005) compared to non-diabetic patients. Preferential
      involvement of the pons and smaller vessels may be characteristics of diabetic
      patients.

PMID- 20814217
TI  - Effects of a platelet gel on early graft revascularization after anterior
      cruciate ligament reconstruction: a prospective, randomized, double-blind,
      clinical trial.
AB  - BACKGROUND: Slow graft healing in bone tunnels and a slow graft ligamentization
      process after anterior cruciate ligament (ACL) reconstruction are some of the
      reasons for prolonged rehabilitation. AIMS: The purpose of this study was to
      determine if the use of platelet gel (PG) accelerates early graft
      revascularization after ACL reconstruction. METHODS: PG was produced from
      autologous platelet-rich plasma and applied locally. We quantitatively evaluated
      the revascularization process in the osteoligamentous interface zone in the bone
      tunnels and in the intra-articular part of the graft by means of contrast
      enhanced magnetic resonance imaging (MRI). RESULTS: After 4-6 weeks, the PG
      treated group demonstrated a significantly higher level of vascularization in the
      osteoligamentous interface (0.33 +/- 0.09) than the control group (0.16 +/- 0.09,
      p < 0.001). In the intra-articular part of the graft, we found no evidence of
      revascularization in either group. CONCLUSION: Locally applied PG enhanced early
      revascularization of the graft in the osteoligamentous interface zone after ACL
      reconstruction.

PMID- 20814218
TI  - Macrophages and dendritic cells for treating kidney disease.
AB  - Based on new understanding of the diverse biological functions of macrophages and
      dendritic cells (DC), the focus of studies on these cells has been expanded from
      their pathogenic role in renal diseases to include their potential to regulate
      inflammation and restore renal architecture and function. By exploiting their
      regulatory function, macrophages or DC have been used to treat experimental renal
      disease following their adoptive transfer. This review summarizes current
      progress in the therapeutic use of macrophages and DC in renal diseases. Key
      issues for ongoing research are discussed.

PMID- 20814219
TI  - Suppression of Par-4 protects human renal proximal tubule cells from apoptosis
      induced by oxidative stress.
AB  - BACKGROUND: Oxidative stress is an important inducer of cell apoptosis and plays
      a key role in the development of renal inflammation. The prostate apoptosis
      response factor-4 (Par-4) gene was originally identified in prostate cells
      undergoing apoptosis. Subsequently, Par-4 was found to possess potent pro
      apoptotic activity in various cellular systems. However, it remains unclear
      whether Par-4 is involved in oxidant injury of renal tubular epithelial cells.
      AIMS: To determine the role of Par-4 in renal proximal tubular cell apoptosis
      induced by oxidative stress. METHODS: Par-4 gene expression was silenced by small
      interfering RNA. Renal proximal tubular cells were then exposed to hydrogen
      peroxide and the effect of Par-4 silencing on apoptosis and expression of
      phosphorylated Akt and vascular endothelial growth factor was determined.
      RESULTS: Hydrogen peroxide induced apoptosis and increased Par-4 expression in
      human renal proximal tubular epithelial cells. Par-4 silencing significantly
      protected renal proximal tubular cells from apoptosis via activating the PI3K/Akt
      signaling pathway as Akt phosphorylation was enhanced. Par-4 silencing also
      ameliorated the downregulation of vascular endothelial growth factor expression
      induced by oxidative stress. CONCLUSION: Par-4 gene silencing resulted in
      PI3K/Akt signaling-dependent inhibition of renal proximal tubular cell apoptosis
      following oxidative stress.

PMID- 20814220
TI  - High glucose upregulates upstream stimulatory factor 2 in human renal proximal
      tubular cells through angiotensin II-dependent activation of CREB.
AB  - BACKGROUND/AIMS: We have previously demonstrated that a transcription factor,
      upstream stimulatory factor 2 (USF2), regulates glucose-induced thrombospondin 1
      expression and transforming growth factor-beta activity in mesangial cells, and
      plays an important role in diabetic glomerulopathy. In this study, we determined
      whether USF2 expression in renal proximal tubular cells is regulated by glucose
      and contributes to diabetic tubulointerstitial fibrosis. METHODS: Human renal
      proximal tubular cells (HK-2 cells) were treated with normal- or high-glucose
      medium for 24 h. After treatment, real-time PCR or immunoblotting was used to
      determine the expression of USF2 and other components of the renin-angiotensin
      system in HK-2 cells. RESULTS: High glucose upregulated USF2 expression and
      increased extracellular matrix accumulation in HK-2 cells; both were inhibited by
      siRNA-mediated USF2 knockdown. In addition, high glucose stimulated
      angiotensinogen and renin expression, increased renin activity, and resulted in
      increased angiotensin II formation. Treatment of HK-2 cells with an angiotensin
      II receptor 1 (AT1) blocker--losartan--prevented high-glucose-induced USF2
      expression and high-glucose-enhanced phosphorylation of CREB (cAMP response
      element-binding protein). CONCLUSION: Our data established that high glucose
      stimulated USF2 expression in HK-2 cells, at least in part, through angiotensin
      II-AT1-dependent activation of CREB, which can contribute to diabetic
      tubulointerstitial fibrosis.

PMID- 20814221
TI  - Transient receptor potential melastatin 6 knockout mice are lethal whereas
      heterozygous deletion results in mild hypomagnesemia.
AB  - BACKGROUND: Hypomagnesemia with secondary hypocalcemia is due to disturbed renal
      and intestinal magnesium (Mg(2+)) (re)absorption. The underlying defect is a
      mutation in the transient receptor potential melastatin type 6 (TRPM6), a Mg(2+)
      permeable ion channel expressed in the kidney and intestine. Our aim was to
      characterize homozygous (-/-) and heterozygous (+/-) TRPM6 knockout mice with
      respect to Mg(2+) homeostasis. METHODS: TRPM6(+/-) mice were bred on a normal
      (0.19% wt/wt Mg(2+)) and high (0.48% wt/wt Mg(2+)) Mg(2+) diet. In the offspring,
      24-hour urinary Mg(2+) and calcium excretion as well as serum concentrations of
      both were determined. TRPM6 mRNA expression in the kidney and colon was measured.
      RESULTS: On the regular diet, 30% of the offspring were TRPM6 wild-type ((+/+)),
      70% were TRPM6(+/-), and none were TRPM6(-/-). The genotypic distribution of the
      litters remained the same on the 0.48% Mg(2+) diet. In TRPM6(+/-) mice on both
      diets, serum Mg(2+) levels were significantly lower, and renal and intestinal
      TRPM6 mRNA expression was reduced. Urinary Mg(2+) excretion was unaffected.
      CONCLUSIONS: Homozygous TRPM6 deletion is embryonic lethal in mice. Heterozygous
      deletion of TRPM6 results in a mild hypomagnesemia. The Mg(2+)-enriched diet
      could not compensate for either embryonic lethality or hypomagnesemia caused by
      TRPM6 deficiency.

PMID- 20814222
TI  - Expression of HGF/c-Met is dynamically regulated in the dorsal root ganglions and
      spinal cord of adult rats following sciatic nerve ligation.
AB  - Hepatocyte growth factor (HGF) and its receptor c-Met play pivotal roles in post
      traumatic regeneration of the nervous system. However, following peripheral nerve
      injury, the role and regulation of the HGF/c-Met system is less clear. Therefore,
      using a sciatic nerve ligation (SNL) model, spatiotemporal changes in HGF and c
      Met expression were detected in the dorsal root ganglions (DRGs) and lumbar
      spinal cords of adult rats. HGF expression following SNL was found to be
      significantly decreased in ipsilateral L4-L5 DRGs from day 3 to day 14, with the
      lowest levels of expression detected on days 5 and 7. In contrast, no significant
      change in HGF expression was detected in the lumbar spinal cords. c-Met
      expression in ipsilateral L4-L5 DRGs and within the ipsilateral dorsal horn was
      found to be significantly up-regulated following SNL, particularly from day 5 to
      day 14, with peak levels of expression detected on days 7 and 14. In contrast, c
      Met levels following SNL consistently remained stable in the spinal ventral horn.
      These findings suggest that the HGF/c-Met system is spatiotemporally regulated by
      a unique pattern of signaling pathways induced by peripheral nerve injury, and
      these pathways have a role in promoting the survival of injured neurons,
      especially adult DRG sensory neurons.

PMID- 20814223
TI  - A comparison of the short-term outcome in patients with acute low-tone
      sensorineural hearing loss.
AB  - PURPOSE OF THE STUDY: We aimed to compare the short-term outcome of patients with
      acute low-tone sensorineural hearing loss (ALHL) treated with steroid alone,
      diuretics alone or combination treatment. PROCEDURES: Between April 2000 and
      March 2009, we retrospectively reviewed the medical records of 156 patients with
      a diagnosis of ALHL. All patients were followed up until improvement or for 8
      weeks from the initial examination. Patients were treated with steroid alone (n =
      49), diuretics alone (n = 40), combination treatment (n = 46) or they received
      neither steroid nor diuretics (n = 21). RESULTS: The steroid-diuretic combination
      therapy for ALHL showed significantly better results than the steroid or diuretic
      treatments alone (p < 0.05). There were no clinically significant differences in
      the outcome between the steroid- and diuretic-alone treatments. CONCLUSION AND
      MESSAGE: The etiology of ALHL is described as both an endolymphatic hydrops and
      an autoimmunological mechanism so that, as expected, the steroid-diuretic
      combination therapy was more effective than the steroid or diuretic treatments
      alone.

PMID- 20814224
TI  - Theophylline and cardiac stress in patients with dyspnea: an observational study.
AB  - BACKGROUND/AIMS: Appreciation of the anti-inflammatory actions of theophylline at
      low serum concentrations has revived the interest in this drug, but its cardiac
      side effects remain a concern. The serum level of N-terminal probrain natriuretic
      peptide (NT-proBNP) is a marker for cardiac stress. This study examined the
      association between theophylline intake and NT-proBNP. METHODS: The effect of
      theophylline on NT-proBNP was prospectively evaluated by multiple regression
      analysis in 753 outpatients referred for pulmonary evaluation of dyspnea.
      RESULTS: Of 548 patients with asthma, chronic obstructive pulmonary disease or
      respiratory muscle weakness, 107 were taking theophylline (median serum
      concentration 8.1 MUg/ml). The theophylline users were older (mean 64.5 +/- 11.6
      vs. 56.5 +/- 16.8 years, p < 0.01), had severer airway obstruction (p < 0.01) and
      had a higher prevalence of heart disease (33.6 vs. 23.1%, p = 0.02) than the
      patients not taking theophylline. Among the patients with heart disease (n =
      138), the adjusted levels of NT-proBNP were lower (p < 0.01) in the theophylline
      treated patients (n = 36) than in the patients not using theophylline (median
      144.5 vs. 236.4 pg/ml). Theophylline had no effect on NT-proBNP in patients
      without heart disease. CONCLUSION: The results of this observational study call
      into question the traditional view that even low-dose theophylline therapy may be
      detrimental in patients with coexisting heart disease.

PMID- 20814225
TI  - Delivering the goods: Activity-induced exocytosis and AMPA receptor insertion
      within a post-synaptic membrane compartment depends on syntaxin 4.

PMID- 20814226
TI  - Fat: Love it to death!

PMID- 20814227
TI  - Molecular basis for an attenuated cytoplasmic dsRNA response in human embryonic
      stem cells.
AB  - The introduction of double stranded RNA (dsRNA) into the cytoplasm of mammalian
      cells usually leads to a potent antiviral response resulting in the rapid
      induction of interferon beta (IFNbeta). This response can be mediated by a number
      of dsRNA sensors, including TLR3, MDA5, RIG-I and PKR. We show here that
      pluripotent human cells (human embryonic stem (hES) cells and induced pluripotent
      (iPS) cells) do not induce interferon in response to cytoplasmic dsRNA, and we
      have used a variety of approaches to learn the underlying basis for this
      phenomenon. Two major cytoplasmic dsRNA sensors, TLR3 and MDA5, are not expressed
      in hES cells and iPS cells. PKR is expressed in hES cells, but is not activated
      by transfected dsRNA. In addition, RIG-I is expressed, but fails to respond to
      dsRNA because its signaling adapter, MITA/STING, is not expressed. Finally, the
      interferon-inducible RNAse L and oligoadenylate synthetase enzymes are also
      expressed at very low levels. Upon differentiation of hES cells into
      trophoblasts, cells acquire the ability to respond to dsRNA and this correlates
      with a significant induction of expression of TLR3 and its adaptor protein TICAM
      1/TRIF. Taken together, our results reveal that the lack of an interferon
      response may be a general characteristic of pluripotency and that this results
      from the systematic downregulation of a number of genes involved in cytoplasmic
      dsRNA signaling.

PMID- 20814229
TI  - tRNA trafficking along the TOR pathway.

PMID- 20814228
TI  - Signaling pathways in renal cell carcinoma.
AB  - Renal cell carcinoma (RCC), the most lethal type of genitourinary cancer, is
      generally resistant to chemotherapy and radiation therapy. Surgical excision of
      the tumor at a localized stage remains the mainstay for curative therapy. A
      number of drugs developed in recent years have shown limited to significant
      efficacy in treating RCC. These drugs act by blocking critical signaling pathways
      associated with RCC tumor growth and survival, and angiogenesis. Beyond well
      validated signaling targets such as VHL, VEGFR and mTOR, additional pathways
      including HGF/c-MET and Wnt/beta-catenin have emerged as important to RCC
      pathogenesis. Mutations in one or more components of these signaling networks may
      affect tumor response to therapy. This review summarizes the state of knowledge
      about signaling pathways in RCC and discusses the known genetic and epigenetic
      alterations that underlie dysregulation of these pathways.

PMID- 20814230
TI  - A role for ATM kinase activity and Mre11 in microhomology-mediated end-joining.

PMID- 20814231
TI  - The flap about ATM & MRE11.

PMID- 20814232
TI  - p16Ink4A, not only a G1 inhibitor?

PMID- 20814233
TI  - Autophagy-independent LC3 function in vesicular traffic.
AB  - As protein folding is an imperfect process, the endoplasmic reticulum (ER)
      contains folding as well as ER-associated degradation (ERAD) machineries. In
      order to prevent premature interruption of folding, ERAD regulators and effectors
      such as EDEM1 and OS-9 are selectively cleared from the ER in so-called
      EDEMosomes to downregulate the degradative activity. The mechanism by which EDEM1
      and OS-9 are subjected to rapid turnover, also known as ERAD tuning, shows
      similarities with, but is clearly distinct from, macroautophagy. Positive strand
      RNA coronaviruses (CoVs) such as the severe acute respiratory syndrome (SARS)-CoV
      and mouse hepatitis virus (MHV), induce in infected cells the formation of
      autophagosome-like, double-membrane vesicles (DMVs) to which their replication
      and transcription complexes are anchored. While it seems clear that CoVs hijack
      ER-derived host cell membranes for replication, the mechanism by which these DMVs
      are assembled has remained completely mysterious.

PMID- 20814234
TI  - Mechanisms of non-apoptotic programmed cell death in diabetes and heart failure.
AB  - Programmed cell elimination is an important pathological mediator of disease.
      Multiple pathways to programmed cell death have been delineated, including
      apoptosis, autophagy and programmed necrosis. Cross-talk between the signaling
      pathways mediating each process has made it difficult to define specific
      mechanisms of in vivo programmed cell death. For this reason, many "apoptotic"
      diseases may involve other death signaling pathways. Recent advances in genetic
      complementation using mouse knock-out models are helping to dissect apoptotic and
      necrotic cell death in different pathological states. The current state of
      research in this area is reviewed, focusing upon new findings describing the role
      of programmed necrosis induced by the mitochondrial permeability transition in
      mouse models of heart failure and diabetes.

PMID- 20814236
TI  - The Norse god of autophagy. Interviewed by Daniel J Klionsky.

PMID- 20814235
TI  - Glucocorticoids downregulate Fyn and inhibit IP(3)-mediated calcium signaling to
      promote autophagy in T lymphocytes.
AB  - T cell receptor activation induces inositol 1,4,5 trisphosphate (IP(3))-mediated
      calcium signaling that is essential for cell metabolism and survival. Moreover,
      inhibitors of IP(3) or pharmacological agents that disrupt calcium homeostasis
      readily induce autophagy. Using a glucocorticoid-sensitive CD4/CD8 positive T
      cell line, we found that dexamethasone prevented both IP(3)-mediated and
      spontaneous calcium signals within a timeframe that correlated with the induction
      of autophagy. We determined that this loss in IP(3)-mediated calcium signaling
      was dependent upon the downregulation of the Src kinase Fyn at the mRNA and
      protein level. Because it has previously been shown that Fyn positively regulates
      IP(3)-mediated calcium release by phosphorylating Type I IP(3) receptors
      (IP(3)R1), we investigated the effect of glucocorticoids on IP(3)R1
      phosphorylation at Tyr353. Accordingly, glucocorticoid-mediated downregulation of
      Fyn prevented IP(3)R1 phosphorylation at Tyr353. Moreover, selective knockdown of
      Fyn or treatment with a Src inhibitor also attenuated IP(3)-mediated calcium
      release and induced autophagy. Collectively, these data indicate that
      glucocorticoids promote autophagy by inhibiting IP(3)-dependent calcium signals.
      These findings carry important therapeutic implications given the widespread use
      of dexamethasone as both a chemotherapeutic and immunosuppressive agent.

PMID- 20814237
TI  - Association of 5'-CpG island hypermethylation of the FHIT gene with lung cancer
      in southern-central Chinese population.
AB  - The promoter methylation of the FHIT gene has been associated with susceptibility
      to different cancers, including a role in the early pathogenesis of lung cancer.
      We investigated the aberrant promoter methylation of FHIT in lung cancer in the
      Han population of southern-central China. Blood samples from 123 lung cancer
      patients of different clinical stage and histological grading and 105 healthy
      control samples were collected. Methylation-specific polymerase chain reaction
      (MSP ) was performed to analyze the methylation status of FHIT. Aberrant promoter
      methylation of the FHIT gene was 34.15% (42/123) in cancer patients, but in none
      of the 105 controls. Significant association was found between the lung cancer
      cases and controls (OR=2.296; 95% CI=1.95-2.705; p < 0.01). Furthermore, we found
      that aberrant promoter methylation of the FHIT gene showed a highly significant
      association with clinical stage I and not with clinical stage IV in lung cancer
      (p < 0.05). These findings suggest FHIT methylation is associated with a higher
      susceptibility and has a prognostic significance in early stage lung cancer in
      the Han population of southern-central China and may represent a marker for
      progressive disease.

PMID- 20814238
TI  - Smac mimetic reverses resistance to TRAIL and chemotherapy in human urothelial
      cancer cells.
AB  - PURPOSE: inhibitors of apoptosis proteins (IAPs) have been shown to contribute to
      resistance of neoplastic cells to chemotherapy and to biologic antineoplastic
      agents. Consequently, new agents are being developed targeting this family of
      proteins. In a panel of bladder cancer cell lines, we evaluated a Smac mimetic
      that antagonizes several IAPs for its suitability for bladder cancer therapy.
      Experimental design: A panel of seven bladder cancer cell lines were evaluated
      for sensitivity to the Smac mimetic compound-A alone, TRAIL alone, chemotherapy
      alone, compound-A plus TRAIL, and compound-A plus chemotherapy by DNA
      fragmentation analysis. IAP levels and caspase activation were examined by
      western blotting. Release of caspase-3 from X-linked inhibitor of apoptosis
      protein (XIAP), the most effective IAP, was assessed by immunoprecipitation and
      western blotting. Finally, siRNA knockdown of XIAP was correlated with the
      sensitivity of cells to apoptosis induced by compound-A plus TRAIL by DNA
      fragmentation and western blotting. RESULTS: single-agent compound-A had little
      effect, but compound-A augmented TRAIL- and chemotherapy-induced apoptosis.
      Immunoblotting showed that combination treatment with compound-A and TRAIL
      resulted in cleavage of procaspase-3 and procaspase-7, activation of which
      irreversibly commits cells to apoptosis. Immunoprecipitation of XIAP showed
      displacement of active caspase-3 fragments from XIAP, supporting the proposed
      mechanism of action. Furthermore, siRNA-mediated silencing of XIAP similarly
      sensitized these cells to apoptosis. EXPERIMENTAL DESIGN: a panel of seven
      bladder cancer cell lines were evaluated for sensitivity to the Smac mimetic
      compound-Alone, TRAIL alone, Chemotherapy alone, compound-A plus TRAIL and
      compound-A plus chemotherapy by DNA fragmentation analysis. IAP levels and
      caspase activation were examined by western blotting. Release of caspase-3 from X
      linked inhibitor of apoptosis protein (XIAP), the most effective IAP, was
      assessed by immunoprecipitation and western blotting. Finally siRNA knockdown of
      XIAP was correlated with the sensitivity of cells to apoptosis induced by
      compound-A plus TRAIL by DNA fragmentation and western blotting. CONCLUSION: our
      results suggest that targeting of XIAP with the Smac mimetic compound-A has the
      potential to augment the effects of a variety of chemotherapeutic and biologic
      therapies in bladder cancer.

PMID- 20814240
TI  - Processing of human telomeres by the Werner syndrome protein.

PMID- 20814241
TI  - Are the conspicuous interdependences of fecundity, longevity and cognitive
      abilities in humans caused in part by p53?
AB  - Recent discoveries indicate that the answers to the questions whether we will
      have children, and if so, how many; for how long we can expect to live; and how
      fast we are at solving complex intellectual problems, may not be independent of
      one another but correlated. Although the influence of the environment on
      fecundity, longevity and cognitive function is, for most of their parts, well
      documented, it is undisputed that genetic factors impact these issues as well. In
      the following I have tried to compile some evidence in support of the suggestion
      that the transcriptional regulator p53 could be one of the molecular
      underpinnings of the chain of causation that must underlie these correlations.

PMID- 20814239
TI  - Oxidative stress in cancer associated fibroblasts drives tumor-stroma co
      evolution: A new paradigm for understanding tumor metabolism, the field effect
      and genomic instability in cancer cells.
AB  - Loss of stromal fibroblast caveolin-1 (Cav-1) is a powerful single independent
      predictor of poor prognosis in human breast cancer patients, and is associated
      with early tumor recurrence, lymph node metastasis and tamoxifen-resistance. We
      developed a novel co-culture system to understand the mechanism(s) by which a
      loss of stromal fibroblast Cav-1 induces a "lethal tumor micro-environment."
      Here, we propose a new paradigm to explain the powerful prognostic value of
      stromal Cav-1. In this model, cancer cells induce oxidative stress in cancer
      associated fibroblasts, which then acts as a "metabolic" and "mutagenic" motor to
      drive tumor-stroma co-evolution, DNA damage and aneuploidy in cancer cells. More
      specifically, we show that an acute loss of Cav-1 expression leads to
      mitochondrial dysfunction, oxidative stress and aerobic glycolysis in cancer
      associated fibroblasts. Also, we propose that defective mitochondria are removed
      from cancer-associated fibroblasts by autophagy/mitophagy that is induced by
      oxidative stress. As a consequence, cancer associated fibroblasts provide
      nutrients (such as lactate) to stimulate mitochondrial biogenesis and oxidative
      metabolism in adjacent cancer cells (the "Reverse Warburg Effect"). We provide
      evidence that oxidative stress in cancer-associated fibroblasts is sufficient to
      induce genomic instability in adjacent cancer cells, via a bystander effect,
      potentially increasing their aggressive behavior. Finally, we directly
      demonstrate that nitric oxide (NO) over-production, secondary to Cav-1 loss, is
      the root cause for mitochondrial dysfunction in cancer associated fibroblasts. In
      support of this notion, treatment with anti-oxidants (such as N-acetyl-cysteine,
      metformin and quercetin) or NO inhibitors (L-NAME) was sufficient to reverse many
      of the cancer-associated fibroblast phenotypes that we describe. Thus, cancer
      cells use "oxidative stress" in adjacent fibroblasts (i) as an "engine" to fuel
      their own survival via the stromal production of nutrients and (ii) to drive
      their own mutagenic evolution towards a more aggressive phenotype, by promoting
      genomic instability. We also present evidence that the "field effect" in cancer
      biology could also be related to the stromal production of ROS and NO species.
      eNOS-expressing fibroblasts have the ability to downregulate Cav-1 and induce
      mitochondrial dysfunction in adjacent fibroblasts that do not express eNOS. As
      such, the effects of stromal oxidative stress can be laterally propagated,
      amplified and are effectively "contagious"--spread from cell-to-cell like a virus
      -creating an "oncogenic/mutagenic" field promoting widespread DNA damage.

PMID- 20814242
TI  - Stem cell pluripotency: alternative modes of transcription regulation.

PMID- 20814243
TI  - The oncogenic role of the ETS transcription factors MEF and ERG.
AB  - Several ETS transcription factors, including MEF/ELF4 and ERG, can function as
      oncogenes and are overexpressed in human cancer. MEF cooperates in tumorigenesis
      in retroviral insertional mutagenesis-based mouse models of cancer and MEF is
      overexpressed in human lymphoma and ovarian cancer tissues via unknown
      mechanisms. ERG (Ets related gene) overexpression or increased activity has been
      found in various human cancers, including sarcomas, acute myeloid leukemia and
      prostate cancer, where the ERG gene is rearranged due to chromosomal
      translocations. We have been examining how MEF functions as an oncogene and
      recently showed that MEF can cooperate with H-Ras(G12V) and can inhibit both p53
      and p16 expression thereby promoting transformation. In fact, in cells lacking
      p53, the absence of Mef abrogates H-Ras(G12V)-induced transformation of mouse
      embryonic fibroblasts, at least in part due to increased p16 expression. We
      discuss the known mechanisms by which the ETS transcription factors MEF and ERG
      contribute to the malignant transformation of cells.

PMID- 20814244
TI  - AKT-ing via microRNA.
AB  - MicroRNAs are involved in almost every aspect of a mammalian cell's
      functionality, from stem cell differentiation to aging and pathogenesis; however,
      their role in immediate cell signaling is less defined. This has been recently
      demonstrated by the rapid increase or decrease of miR-21's abundance within
      minutes of activation or inhibition of the AKT pathway, respectively, which
      mediates its regulation of Fas ligand (FasL) and phosphatase and tensin homologue
      deleted on chromosome 10 (PTEN) expression, among other targets. Conversely, AKT
      induces rapid downregulation of miR-199a-5p to effect upregulation of hypoxia
      inducible factor 1alpha Hif-1alpha and sirtuin 1 (Sirt1). This suggests that
      posttranscriptional mechanisms regulate miRNAs' processing and/or stability to
      induce the rapid fluctuation in their levels. In support, a growing number of
      studies are showing specific posttranscriptional regulation of miRNAs. The data
      potentially explain how AKT, and plausibly other signaling pathways, can
      specifically and promptly modulate a gene's translation while circumventing the
      need for transcription during transient signaling events. In this article we
      present our views regarding cell signaling via miRNAs.

PMID- 20814245
TI  - Gli3 mediates cell survival and sensitivity to cyclopamine in pancreatic cancer.
AB  - Activation of the hedgehog (HH) pathway plays a critical role in the development
      and continued growth of pancreatic adenocarcinoma (PAC). Cyclopamine, a HH
      pathway inhibitor, has been shown to suppress PAC cell proliferation in vitro and
      in vivo. However, the molecular basis of response to cyclopamine has not been
      fully elucidated nor have genes that predict sensitivity to this compound been
      identified. To better understand these features of HH pathway inhibition, we
      evaluated the biological and molecular effects of cyclopamine in vitro. The
      viability of 9 human PAC cell lines following cyclopamine exposure was determined
      using MTS assay. Proliferation and induction of apoptosis in treated cells were
      examined by bromo-deoxyuridine incorporation, caspase activation, and
      mitochondrial membrane potential. Gene expression before and after cyclopamine
      treatment was determined using Taqman real-time quantitative polymerase chain
      reaction (RTQ-PCR) and Taqman low-density array (TLDA). Among the cell lines
      examined, cyclopamine IC50 values ranged from 8.79 to >30 uM. Response to
      cyclopamine included reduced cell proliferation and induction of apoptosis with
      and without mitochondrial membrane depolarization. Regression analysis revealed
      that GLI3 expression significantly correlated with cyclopamine resistance (r =
      0.80; p = 0.0102). Knockdown of GLI3 using siRNAs increased sensitivity to
      cyclopamine. In addition, GLI3 siRNAs decreased PAC cell viability and reduced
      expression of genes involved in HH signaling (Patched 1 and GLI1) and cell
      proliferation, similar to cyclopamine. These effects were not observed in PAC
      cells with undetectable GLI3 expression. These data suggest that Gli3 mediates
      cell survival and sensitivity to cyclopamine in pancreatic cancer.

PMID- 20814246
TI  - Four metazoan autophagy genes regulate cargo recognition, autophagosome formation
      and autolysosomal degradation.
AB  - The mechanism responsible for induction and maturation of autophagosomes in
      multicellular organisms is poorly understood. We performed genetic screens in C.
      elegans and identified three essential autophagy genes, epg-3, -4 and -5, which
      have highly conserved homologs in mammals, but are absent in yeast. We also
      identified a nematode-specific gene, epg-2, that is required for degradation of
      components of the specialized protein aggregates, called PGL granules. epg-2, -3,
      -4 and -5 define discrete genetic steps of the autophagy pathway. We further
      demonstrated that mammalian homologs of EPG-3, -4 and -5 are essential for
      starvation-induced autophagy. Our study establishes C. elegans as a model to
      identify components of the basal autophagy pathway specific to higher eukaryotes
      and to further assemble these genes into genetic pathways.

PMID- 20814247
TI  - Small-molecule inducer of cancer cell polyploidy promotes apoptosis or
      senescence: Implications for therapy.
AB  - Polyploidy results from deregulated cell division and has been considered an
      undesirable event leading to increased mutation rate and cancer development.
      However, polyploidy may also render cancer cells more vulnerable to chemotherapy.
      Here, we identify a small-molecule inducer of polyploidy, R1530, which interferes
      with tubulin polymerization and mitotic checkpoint function in cancer cells,
      leading to abortive mitosis, endoreduplication and polyploidy. In the presence of
      R1530, polyploid cancer cells underwent apoptosis or became senescent which
      translated into potent in vitro and in vivo efficacy. Normal proliferating cells
      were resistant to R1530-induced polyploidy thus supporting the rationale for
      cancer therapy by induced polyploidy. Mitotic checkpoint kinase BubR1 was found
      downregulated during R1530-induced exit from mitosis, a likely consequence of
      PLK4 inhibition. BubR1 knockdown in the presence of nocodazole induced an R1530
      like phenotype, suggesting that BubR1 plays a key role in polyploidy induction by
      R1530 and could be exploited as a target for designing more specific polyploidy
      inducers.

PMID- 20814248
TI  - The angiogenic profile of colorectal cancer patients following open or
      laparoscopic colectomy.

PMID- 20814249
TI  - Autophagic receptors Nbr1 and p62 coregulate skeletal remodeling.
AB  - Skeletal remodeling is an ongoing process requiring the coordinated action of
      different cell types to maintain homeostatic control of bone synthesis and
      degradation. Mutations in p62/SQSTM1 are associated with sporadic and 5q35-linked
      Paget Disease of Bone (PDB), characterized by focal increased bone turnover.
      These mutations cluster in the ubiquitin associated (UBA) domain and are thought
      to lead to enhancement of NFkappaB pathway activation involved in
      osteoclastogenesis and hyper-responsiveness to receptor activator of nuclear
      factorkappaB ligand (RANKL). The structurally similar selective autophagic
      receptor, Nbr1, binds to LC3 and p62 and is sequestered into autophagosomes,
      whereas it accumulates in autophagic-deficient tissues. We have shown that
      truncation of Nbr1 in a murine model, where it can still interact with p62 but
      not LC3, leads to increased osteoblast differentiation and activity in vivo. This
      results in an age-dependent increase in bone mass and bone mineral density. This
      is a molecular consequence of loss of autophagy receptor function via deletion of
      its C-terminal UBA domain, and/or modulation of the p38 MAPK cellular signaling
      pathway.

PMID- 20814251
TI  - Introduction. Genetics of developmental and behavioral disorders in children.

PMID- 20814250
TI  - No association between XRCC1 polymorphisms and survival in non-small-cell lung
      cancer patients treated with platinum-based chemotherapy.
AB  - PURPOSE: genetic polymorphisms in DNA repair genes are thought to represent
      important determinants of platinum drug efficacy. The current study investigated
      whether single nucleotide polymorphisms (SNPs) in the X-ray repair cross
      complementing protein 1 (XRCC1) gene are associated with survival in non-small
      cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy.
      EXPERIMENTAL DESIGN: a total of 199 platinum-treated patients with stage III-IV
      NSCLC were recruited. Overall survival (OS) and progression-free survival (PFS)
      according to genotypes and haplotypes were analyzed using Kaplan-Meier method and
      assessed by log-rank test. Hazard ratios (HRs) were calculated using Cox
      proportional hazards models by adjusting for clinical factors. RESULTS: during
      the median 26.5 months of follow-up, 159 deaths occurred. Regarding XRCC1
      Arg194Trp, Arg280His, and Arg399Gln genotypes, no significant effects on survival
      were observed, although the 280Arg/His genotype was associated with a borderline
      significant higher median survival time (20.0 months for Arg/His versus 16.0
      months for Arg/Arg; P = 0.131). Moreover, no significant association of
      haplotypes with survival was found. CONCLUSIONS: this study showed no influence
      of the XRCC1 Arg194Trp, Arg280His, and Arg399Gln polymorphisms on survival in
      advanced NSCLC patients with platinum-based chemotherapy.

PMID- 20814252
TI  - Behavioral genetic approach to the study of dyslexia.
AB  - OBJECTIVE: Dyslexia is a prominent focus of practitioners, educators, and
      researchers because of the myriad consequences of failing to read proficiently.
      The aim of this study was to provide a brief overview of how twin studies can
      offer insight on the cause of many human behaviors and disorders including
      dyslexia, discuss common misconceptions regarding findings from behavioral
      genetic studies, briefly review the evidence on the relationship between genes,
      environment, and dyslexia, and finally present some findings from a large-scale
      twin study on reading and dyslexia. METHOD: Participants were twins from a large
      ethnically and socioeconomically diverse twin sample in an ongoing longitudinal
      study of reading and dyslexia. Heritabilities of reading ability and dyslexia
      were calculated for 1,024 first grade twins on a standardized reading measure.
      Children were identified as dyslexic if they scored at the 15th percentile or
      below on a reading measure. RESULTS: Relatively high heritabilities were observed
      for both reading ability and dyslexia indicating substantial genetic influences.
      Further, results indicated some overlap of genetic factors influencing reading
      ability and dyslexia. CONCLUSIONS: Behavioral genetic studies offer a means of
      understanding the cause of dyslexia. This study extended research to a more
      diverse sample than extant studies and found lower heritability estimates of
      reading ability and dyslexia, but a similar pattern of results indicating
      possible genetic overlap. Twin studies provide perspective for discoveries of
      specific genes involved in dyslexia by quantifying the amount of variance waiting
      to be accounted for by genes while simultaneously providing an impetus to
      continue working on efforts for environmental intervention.

PMID- 20814254
TI  - Understanding the complex etiologies of developmental disorders: behavioral and
      molecular genetic approaches.
AB  - OBJECTIVE: This article has 2 primary goals. First, a brief tutorial on
      behavioral and molecular genetic methods is provided for readers without
      extensive training in these areas. To illustrate the application of these
      approaches to developmental disorders, etiologically informative studies of
      reading disability (RD), math disability (MD), and attention-deficit
      hyperactivity disorder (ADHD) are then reviewed. Implications of the results for
      these specific disorders and for developmental disabilities as a whole are
      discussed, and novel directions for future research are highlighted. METHOD:
      Previous family and twin studies of RD, MD, and ADHD are reviewed systematically,
      and the extensive molecular genetic literatures on each disorder are summarized.
      To illustrate 4 novel extensions of these etiologically informative approaches,
      new data are presented from the Colorado Learning Disabilities Research Center,
      an ongoing twin study of the etiology of RD, ADHD, MD, and related disorders.
      CONCLUSIONS: RD, MD, and ADHD are familial and heritable, and co-occur more
      frequently than expected by chance. Molecular genetic studies suggest that all 3
      disorders have complex etiologies, with multiple genetic and environmental risk
      factors each contributing to overall risk for each disorder. Neuropsychological
      analyses indicate that the 3 disorders are each associated with multiple
      neuropsychological weaknesses, and initial evidence suggests that comorbidity
      between the 3 disorders is due to common genetic risk factors that lead to slow
      processing speed.

PMID- 20814255
TI  - Etiologies and molecular mechanisms of communication disorders.
AB  - Quantitative behavioral genetic studies have made it clear that communication
      disorders such as reading disability, language impairment, and autism spectrum
      disorders follow some basic principles: (1) complex disorders have complex
      causes, in which each clinical disorder is influenced by a number of separate
      genes; and (2) at least some behaviorally related disorders are influenced by the
      same genes. Recent advances in molecular and statistical methods have confirmed
      these principles and are now leading to an understanding of the genes that may be
      involved in these disorders and how their disruption may affect the development
      of the brain. The prospect is that the genes involved in these disorders will
      define a network of interacting neurologic functions and that perturbations of
      different elements of this network will produce susceptibilities for different
      disorders. Such knowledge would clarify the underlying deficits in these
      disorders and could lead to revised diagnostic conceptions. However, these goals
      are still in the future. Identifying the individual genes in such a network is
      painstaking, and there have been seemingly contradictory studies along the way.
      Improvements in study design and additional functional analysis of genes are
      gradually clarifying many of these issues. When combined with careful phenotypic
      studies, molecular genetic studies have the potential to refine the clinical
      definitions of communication disorders and influence their remediation.

PMID- 20814257
TI  - Epigenetics, copy number variation, and other molecular mechanisms underlying
      neurodevelopmental disabilities: new insights and diagnostic approaches.
AB  - The diagnostic evaluation of children with intellectual disability (ID) and other
      neurodevelopmental disabilities (NDD) has become increasingly complex in recent
      years owing to a number of newly recognized genetic mechanisms and sophisticated
      methods to diagnose them. Previous studies have attempted to address the
      diagnostic yield of finding a genetic cause in ID. The results have varied widely
      from 10% to 81%, with the highest percentage being found in studies using new
      array comparative genomic hybridization methodology especially in autism.
      Although many cases of ID/NDD result from chromosomal aneuploidy or structural
      rearrangements, single gene disorders and new categories of genome modification,
      including epigenetics and copy number variation play an increasingly important
      role in diagnosis and testing. Epigenetic mechanisms, such as DNA methylation and
      modifications to histone proteins, regulate high-order DNA structure and gene
      expression. Aberrant epigenetic and copy number variation mechanisms are involved
      in several neurodevelopmental and neurodegenerative disorders including Rett
      syndrome, fragile X syndrome, and microdeletion syndromes. This review will
      describe a number of the molecular genetic mechanisms that play a role in
      disorders leading to ID/NDD and will discuss the categories and technologies for
      diagnostic testing of these conditions.

PMID- 20814258
TI  - Behavior, brain, and genome in genomic disorders: finding the correspondences.
AB  - OBJECTIVE: Within the last decade or so, there has been an acceleration of
      research attempting to connect specific genetic lesions to the patterns of brain
      structure and activation. This article comments on observations that have been
      made based on these recent data and discusses their importance for the field of
      investigations into developmental disorders. METHODS: In making these
      observations, the authors focus on one specific genomic lesion, the well-studied,
      yet still incompletely understood, 22q11.2 deletion syndrome. RESULTS: The
      authors demonstrate the degree of variability in the phenotype that occurs at
      both the brain and behavioral levels of genomic disorders and describe how this
      variability is, on close inspection, represented at the genomic level.
      CONCLUSION: The authors emphasize the importance of combining genetic/genomic
      analyses and neuroimaging for research and for future clinical diagnostic
      purposes and for the purposes of developing individualized, patient-tailored
      treatment and remediation approaches.

PMID- 20814260
TI  - An overview of newborn screening.
AB  - This review of newborn screening examines the beginning of screening with the
      story of phenylketonuria and explores the principles of screening and the
      criteria with which disorders were added to newborn screening panels. The
      explosion of tests that are screened for followed the adoption of tandem mass
      spectrometry (MS-MS) technology. The inequity of state newborn screening panels
      was brought to the forefront with an American Academy of Pediatrics task force
      report in 2000 that called for a national panel. The American College of Medical
      Genetics convened an expert panel to produce such a panel. In 2006, they
      published their panel of disorders, recommending a panel of 29 core disorders and
      25 additional secondary targets. Ethical arguments about newborn screening have
      resurfaced with the recent expansion of testing that include arguments about
      consent, mandatory participation, benefits to those screened, and cost-both to
      the individual and society. Finally, the future direction of screening is
      discussed. Newborn screening is undergoing rapid expansion. The addition of tests
      involves ethical, financial, and social pressures.

PMID- 20814256
TI  - Emerging pharmacotherapies for neurodevelopmental disorders.
AB  - A growing and interdisciplinary translational neuroscience research effort for
      neurodevelopmental disorders (NDDs) is investigating the mechanisms of
      dysfunction and testing effective treatment strategies in animal models and, when
      possible, in the clinic. NDDs with a genetic basis have received particular
      attention. Transgenic animals that mimic genetic insults responsible for disease
      in man have provided insight about mechanisms of dysfunction, and, surprisingly,
      have shown that cognitive deficits can be addressed in adult animals. This review
      will present recent translational research based on animal models of genetic
      NDDs, as well as pharmacotherapeutic strategies under development to address
      deficits of brain function for Down syndrome, fragile X syndrome, Rett syndrome,
      neurofibromatosis-1, tuberous sclerosis, and autism. Although these disorders
      vary in underlying causes and clinical presentation, common pathways and
      mechanisms for dysfunction have been observed. These include abnormal gene
      dosage, imbalance among neurotransmitter systems, and deficits in the
      development, maintenance and plasticity of neuronal circuits. NDDs affect
      multiple brain systems and behaviors that may be amenable to drug therapies that
      target distinct deficits. A primary goal of translational research is to replace
      symptomatic and supportive drug therapies with pharmacotherapies based on a
      principled understanding of the causes of dysfunction. Based on this principle,
      several recently developed therapeutic strategies offer clear promise for
      clinical development in man.

PMID- 20814263
TI  - Serendipity in science: a disappearing element?

PMID- 20814261
TI  - Autistic spectrum disorder in a 9-year-old girl with macrocephaly.
AB  - CASE: A 9-year-old girl was brought for consultation due to autism and a large
      head circumference. Her birth weight was 6 pounds after a 37-week gestation to a
      healthy G3P1SAb 2 mother. She had been a healthy child with the exception of the
      development of a lipomatous lesion on the left thigh, requiring surgical removal
      at age 3(1/2) years. Autism was diagnosed at age 5 yr by a developmental
      pediatrician. She did not have cognitive disabilities or a history of seizures.
      The family history was notable for maternal infertility with no history of
      developmental disabilities, large body or head size, or malignancy in close
      relatives.On physical examination, she was a mildly obese girl with a large head.
      Her weight was 50.4 kg (>95%), height was 142 cm (90%), and head circumference
      was 60.3 cm (significantly >95%; 4SDs above the mean). Examination of her skin
      was notable for a 2 x 6 cm scar on her left thigh and three cafe au lait macules
      on her trunk. She was Tanner Stage I. Mild hypotonia with normal deep tendon
      reflexes was observed; the remainder of the neurological examination was
      normal.Laboratory studies included high-resolution chromosomes, fragile X,
      metabolic screens, and methylation for Prader Willie Syndrome and Angelman
      Syndrome; all these studies were normal. Molecular testing of the PTEN gene
      (phosphatase and tensin homolog protein) revealed a R355X mutation, consistent
      with the diagnosis of Bannayan-Riley-Ruvalcaba Syndrome (BRRS). In parents and
      siblings, PTEN test results were negative for mutations.Endocrine evaluation
      revealed an abnormal thyroid nodule on ultrasound. Computed tomography and
      positron emission tomography scans raised suspicion of malignancy. She underwent
      a total thyroidectomy; the pathology report revealed a thyroid adenoma with
      Hurthle cells. She was treated with thyroid hormone replacement therapy.

PMID- 20814259
TI  - Neurodevelopmental manifestations of mitochondrial disease.
AB  - Mitochondrial disease is an increasingly recognized but widely heterogeneous
      group of multisystemic disorders that commonly involve severe neurodevelopmental
      manifestations in childhood. This review explores the presentation, genetic
      basis, and diagnostic evaluation of primary mitochondrial disease. Emphasis is
      placed on neurodevelopmental findings that may be encountered by a Developmental
      Pediatrician that should provoke consideration of a mitochondrial disorder. The
      inheritance patterns and mechanisms by which mutations in genes located in either
      the nuclear or mitochondrial genomes can cause mitochondrial diseases are
      discussed. A general overview of the current diagnostic evaluation that can be
      readily initiated by the Developmental Pediatrician is provided, along with a
      summary of currently available treatment options.

PMID- 20814265
TI  - Fall.

PMID- 20814268
TI  - Bringing comfort to Haiti.
AB  - On January 12, 2010, a devastating earthquake ravaged one of the poorest nations
      in the western hemisphere. A week later, the U.S. Naval Ship Comfort was anchored
      off Port-au-Prince to perform a mission of mercy for hundreds of critically
      injured victims of this disaster. The staff of the U.S. Naval Ship Comfort
      included military as well as civilian volunteer healthcare professionals, working
      as a team day and night under adverse conditions to save lives and optimize
      outcomes for the survivors.

PMID- 20814270
TI  - The ethical dilemmas of aesthetic medicine: what every provider should consider.
AB  - The purpose of aesthetic medicine is embellishment and enhancement. As these
      procedures are elective in nature, media messages and misleading advertisements
      do influence those consumers seeking to improve or enhance their appearance. The
      role of provider demands that prudent guide these treatment options and not only
      succumb to patient demands. This article discusses the ethical principles of
      autonomy, beneficence, nonmaleficence, and justice, and presents a framework to
      guide practice to enhance resolution of ethical dilemmas confronting the provider
      of aesthetic medicine.

PMID- 20814272
TI  - Wound care for the plastic surgery nurse.
AB  - The plastic surgery nurse is often confronted with various acute and chronic
      wounds. Appropriate wound care can facilitate healing, improve quality of life,
      decrease pain, and improve cosmesis. Yet, with more than 5,000 products on the
      market today, it can be difficult to choose the appropriate product. This article
      reviews some of the basic principles of wound healing and patient assessment and
      then presents a framework from which to develop a plan of care using appropriate
      wound care products. Appropriate product selection based on patient assessment
      and clearly defined wound-healing goals can lead to improved healing and saved
      health care resources.

PMID- 20814274
TI  - Local complications after cosmetic breast augmentation: results from the Danish
      Registry for Plastic Surgery of the Breast.
AB  - BACKGROUND: Prospective long-term data on the occurrence of complications
      following breast augmentation are sparse and the reported frequencies differ
      substantially. METHODS: The Danish Registry for Plastic Surgery of the Breast has
      prospectively registered preoperative, perioperative, and postoperative data for
      women undergoing breast augmentation in Denmark since 1999. From the Registry,
      the authors identified 5373 women with a primary cosmetic breast augmentation
      between 1999 and 2007. The authors calculated incidence proportions of adverse
      clinical outcomes within three time intervals (0 to 30 days, 0 to 3 years, and 0
      to 5 years) after primary implantation. Outcomes of primary interest were
      capsular contracture, asymmetry/ displacement of the implant, hematoma, and
      infection. RESULTS: During the entire follow-up period (mean, 3.8 years; range,
      0.1 to 8.7 years), 16.7 percent of the women were registered with an adverse
      event and 4.8 percent of the women were registered with a surgery-requiring
      complication. The most common adverse events within 30 days were hematoma (1.1
      percent) and infections (1.2 percent), whereas the most common adverse events
      within 5 years were change of tactile sense (8.7 percent) and asymmetry/
      displacement of implant (5.2 percent). Within 5 years, 1.7 percent of the women
      had a record of severe capsular contracture. Displacement/asymmetry and capsular
      contracture were the most frequent indications for reoperation with removal or
      exchange of the implant. CONCLUSIONS: Population-based complication frequencies
      among women with cosmetic breast augmentation in a Danish nationwide implant
      registry were generally lower than those reported in other studies, although
      frequencies of complications increased with length of follow-up.

PMID- 20814275
TI  - Psychosocial predictors of an interest in cosmetic surgery among young Norwegian
      women: a population-based study.
AB  - BACKGROUND: The present study investigated psychosocial factors expected to
      predict an interest in cosmetic surgery. It was hypothesized that body dysmorphic
      disorder-like symptoms, personality, interpersonal attachment insecurity, low
      self-esteem, poor body image, dissatisfaction with sexual life, distorted eating
      behavior, emotional distress, low education, poor relationship with parents and
      friends, teasing history, social acceptance of cosmetic surgery, and low level of
      physical activity would relate to an interest in cosmetic surgery. METHODS:
      Questionnaire data were obtained from 1880 participants who responded to a survey
      distributed to a representative sample of 3500 Norwegian women between 18 and 35
      years of age living in the two northernmost counties. Data were analyzed by
      univariate and multiple logistic regression analyses. RESULTS: Multiple
      regression analyses showed that an interest in cosmetic surgery was positively
      related to body dysmorphic disorder-like symptoms, body image orientation, having
      children, been teased for appearance, knowing someone who has had cosmetic
      surgery, and being recommended cosmetic surgery. Agreeability, body image
      evaluation, education, and quality of relationship with parents were negatively
      related to an interest in cosmetic surgery. CONCLUSIONS: The study gives new
      insights into psychosocial factors predicting an interest in cosmetic surgery. In
      addition to previously known predictors, having been teased for appearance and
      having children were positive predictors, whereas education and quality of
      relationship with parents were negative predictors of an interest in cosmetic
      surgery. The results may contribute to a better understanding of the various
      factors that may motivate an individual to undergo cosmetic surgery.

PMID- 20814276
TI  - Hot topic: medical tourism.

PMID- 20814277
TI  - Commentary: alternative burn care in Israel: and it is spreading to the States.
AB  - This article outlines effective at-home therapies for burn care, both first aid
      and post-hospital. Therapies for reducing the need for grafts and pressure
      dressings are proposed. The practice of rubbing the burn wound is challenged.
      This article is based on the author's firsthand experiences and proposes that
      alternative therapies be introduced into the hospital and home setting.

PMID- 20814278
TI  - Calciphylaxis: a review.

PMID- 20814280
TI  - Comparison of bupivacaine, ropivacaine, and levobupivacaine in an equal dose and
      concentration for sympathetic block in dogs.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to compare the potency of
      bupivacaine, ropivacaine, and levobupivacaine in an equal dose and concentration
      for sympathetic block. METHODS: We measured mean arterial pressure, heart rate
      (HR), and right and left brachial artery blood flow (BABF) before and after
      cervicothoracic sympathetic block in 24 dogs. The experimental protocol was
      designed as follows: (1) left cervicothoracic sympathetic block with 1.0 mL of
      0.25% bupivacaine (n = 8), (2) left cervicothoracic sympathetic block with 1.0 mL
      of 0.25% ropivacaine (n = 8), and (3) left cervicothoracic sympathetic block with
      1.0 mL of 0.25% levobupivacaine (n = 8). RESULTS: Mean arterial pressure and
      heart rate did not change significantly throughout the study in either group.
      Left cervicothoracic sympathetic block with 0.25% bupivacaine increased left BABF
      significantly from 5 to 100 mins after the block (baseline, 100%; peak at 20 mins
      after the block, 218% +/- 48%; P < 0.01). Left cervicothoracic sympathetic block
      with 0.25% ropivacaine increased left BABF significantly from 5 to 100 mins after
      the block (baseline, 100%; peak at 10 mins after the block, 254 +/- 38%; P <
      0.01). Left cervicothoracic sympathetic block with 0.25% levobupivacaine
      increased left BABF significantly from 5 to 80 mins after the block (baseline,
      100%; peak at 20 mins after the block, 183% +/- 38%; P < 0.01). CONCLUSIONS:
      Ropivacaine may induce a greater increase in vasodilation than bupivacaine and
      levobupivacaine at the same dose and concentration for sympathetic block in dogs.

PMID- 20814282
TI  - Dexamethasone added to mepivacaine prolongs the duration of analgesia after
      supraclavicular brachial plexus blockade.
AB  - BACKGROUND AND OBJECTIVES: Corticosteroids have been used successfully to prolong
      the duration of local anesthetic action after peripheral nerve and epidural
      blockade. We hypothesized that the addition of dexamethasone to mepivacaine would
      prolong the duration of analgesia after ultrasound-guided supraclavicular
      brachial plexus block for patients undergoing upper-limb surgery. METHODS: After
      Federal Health Department and institutional review board approval, 45 adult
      patients undergoing elective hand or forearm surgery under supraclavicular
      brachial plexus blockade were randomized to receive either 30 mL mepivacaine 1.5%
      plus dexamethasone 8 mg (4 mg/mL), or 30 mL mepivacaine 1.5% plus 2 mL normal
      saline. The primary outcome measure was duration of analgesia. Secondary outcomes
      included onset times of sensory and motor blockade, pain and satisfaction scores,
      analgesic consumption, and block-related complications. RESULTS: Patient
      characteristics were similar between groups. The median duration of analgesia was
      significantly prolonged in the Dexamethasone group (332 mins; interquartile
      range, 225-448 mins) compared with the Normal Saline group (228 mins;
      interquartile range, 207-263 mins; P = 0.008). The onset times of sensory and
      motor block were similar between the groups. Complications were minor and
      transient and did not differ between groups at 2 weeks postoperatively.
      CONCLUSIONS: The addition of dexamethasone to mepivacaine prolongs the duration
      of analgesia but does not reduce the onset of sensory and motor blockade after
      ultrasound-guided supraclavicular block compared with mepivacaine alone.

PMID- 20814281
TI  - Perioperative pulmonary circulatory changes during bilateral total hip
      arthroplasty under regional anesthesia.
AB  - BACKGROUND AND OBJECTIVES: The transient and rarely clinically relevant effect of
      bone and cement embolization during unilateral joint arthroplasty is a known
      phenomenon. However, available studies do not address events surrounding
      bilateral total hip arthroplasties, during which embolic load is presumably
      doubled. To elucidate events surrounding this increasingly used procedure and
      assess the effect on the pulmonary hemodynamics in the intraoperative and
      postoperative periods, we studied 24 subjects undergoing cemented bilateral total
      hip arthroplasty during the same anesthetic session. MATERIALS: Twenty-four
      patients without previous pulmonary history undergoing cemented bilateral total
      hip arthroplasty under controlled epidural hypotension were enrolled. Pulmonary
      artery catheters were inserted and hemodynamic variables were recorded at
      baseline, 5 mins after the implantation of each hip joint, 1 hr and 1 day after
      surgery. Mixed venous blood gases and complete blood counts were analyzed at
      every time point. RESULTS: An increase in pulmonary vascular resistance was
      observed after the second but not the first hip implantation when compared with
      values at incision. Pulmonary vascular resistance remained elevated 1 hr after
      surgery. Pulmonary artery pressures were significantly elevated on postoperative
      day 1 compared with those at baseline. The white blood cell count increased in
      response to the second hip implantation but not the first compared with incision.
      CONCLUSIONS: The embolization of material during bilateral total hip arthroplasty
      is associated with prolonged increases in pulmonary artery pressures and vascular
      resistance, particularly after completion of the second side. Performance of
      bilateral procedures should be cautiously considered in patients with diseases
      suggesting decreased right ventricular reserve.

PMID- 20814284
TI  - Experience with 724 epidurograms for epidural catheter placement in pediatric
      anesthesia.
AB  - INTRODUCTION: Epidural analgesia via continuous catheters, placed either via the
      caudal approach or directly at the desired level, is a commonly used technique in
      children. It is particularly important that these catheters are placed correctly
      because most are placed under general anesthesia and require deep sedation or
      repeat general anesthesia for replacement if malfunctioning. Ideally, correct
      placement should be confirmed at the time of insertion. METHODS: We combined the
      experience of 2 academic teaching hospitals that both perform routine
      epidurography for the placement of epidural catheters in children. The data from
      2 quality assurance regional anesthesia databases were screened for unrecognized
      misplacements of epidural catheters. RESULTS: Of a total of 724 epidurograms,
      45.8% were caudal catheters, 9.6% were lumbar catheters, and 32.3% were thoracic
      catheters. Epidurograms detected 12 (1.6%) unexpected misplacements: 4 were
      intrathecal, 3 were intravenous, and 3 were intraperitoneal. CONCLUSIONS: Our
      experiments suggest that confirmation of epidural catheter placement via
      epidurogram is highly efficacious. Epidurography is the only currently available
      technique that accomplishes all of the following: (a) confirms correct placement,
      (b) rules out incorrect anatomic space, and (c) predicts analgesic coverage.

PMID- 20814283
TI  - Perineural dexmedetomidine provides an increased duration of analgesia to a
      thermal stimulus when compared with a systemic control in a rat sciatic nerve
      block.
AB  - BACKGROUND AND OBJECTIVES: The present study was designed to test the hypothesis
      that perineural dexmedetomidine provides a longer duration of analgesia than the
      same dose given subcutaneously in a peripheral nerve block in rats. METHODS:
      Fifty-four rats received unilateral sciatic nerve blocks along with a
      subcutaneous injection at the base of the neck by a blinded investigator assigned
      at random. Combinations were as follows: perineural ropivacaine alone and
      subcutaneous (SQ) saline, perineural ropivacaine plus dexmedetomidine and SQ
      saline, perineural ropivacaine and SQ dexmedetomidine, perineural dexmedetomidine
      alone and SQ saline, and perineural saline and SQ dexmedetomidine. The
      ropivacaine concentration was fixed at 0.5%, and the dose of dexmedetomidine was
      20.0 microg/kg (119.3 micromol/L). Sensory analgesia was assessed by paw
      withdrawal latency (PWL) to a thermal stimulus every 30 mins after the block for
      a minimum of 240 mins or until the return of normal sensory function. The
      unblocked paw served as the control for assessment of systemic, centrally
      mediated analgesia. Between-group and within-group comparisons of PWL were
      obtained for measures from operative and control paws. RESULTS: The analgesic
      effect of perineural dexmedetomidine was superior to that of subcutaneous
      dexmedetomidine in ropivacaine sciatic nerve blocks from time points 120 to 210
      mins (P < 0.017). Perineural dexmedetomidine also showed less systemic effect as
      measured by the unblocked control paw at multiple time points (P < 0.05).
      Perineural dexmedetomidine alone provided a brief, partial sensory block.
      CONCLUSIONS: Sensory analgesia provided by dexmedetomidine added to ropivacaine
      for peripheral nerve blocks in rat is a peripherally mediated effect.

PMID- 20814285
TI  - Correlation among ultrasound, cross-sectional anatomy, and histology of the
      sciatic nerve: a review.
AB  - BACKGROUND AND OBJECTIVES: Efficient identification of the sciatic nerve (SN)
      requires a thorough knowledge of its topography in relation to the surrounding
      structures. Anatomic cross sections in similar oblique planes as observed during
      SN ultrasonography are lacking. A survey of sonoanatomy matched with ultrasound
      views of the major SN block sites will be helpful in pattern recognition,
      especially when combined with images that show the internal architecture of the
      nerve. METHODS: From 1 cadaver, consecutive parts of the upper leg corresponding
      to the 4 major blocks sites were sectioned and deeply frozen. Using
      cryomicrotomy, consecutive transverse sections were acquired and photographed at
      78-microm intervals, along with histologic sections at 5-mm intervals.
      Multiplanar reformatting was done to reconstruct the optimal planes for an
      accurate comparison of ultrasonography and gross anatomy. The anatomic and
      histologic images were matched with ultrasound images that were obtained from 2
      healthy volunteers. RESULTS: By simulating the exact position and angulation as
      in the ultrasonographic images, detailed anatomic overviews of SN and adjacent
      structures were reconstructed in the gluteal, subgluteal, midfemoral, and
      popliteal regions. Throughout its trajectory, SN contains numerous fascicles with
      connective and adipose tissues. CONCLUSIONS: In this study, we provide an optimal
      matching between histology, anatomic cross sections, and short-axis ultrasound
      images of SN. Reconstructing ultrasonographic planes with this high-resolution
      digitized anatomy not only enables an overview but also shows detailed views of
      the architecture of internal SN. The undulating course of the nerve fascicles
      within SN may explain its varying echogenic appearance during probe manipulation.

PMID- 20814286
TI  - Subepineurial injection in ultrasound-guided interscalene needle tip placement.
AB  - INTRODUCTION: The neural elements of the brachial plexus between the anterior and
      middle scalene muscles are readily visible by ultrasound. However, the epineurium
      of these nerve structures is difficult to discern on ultrasound imaging because
      of the proximity of the scalene muscles to the nerve elements, and this may lead
      to unintentional subepineurial injection (SEI). To evaluate whether typical
      needle tip placement under ultrasound guidance results in SEI, as opposed to
      extraneural injection, we undertook this cadaver study. MATERIALS AND METHODS:
      Six nonpreserved cadavers served as subjects for 10 injections. After imaging
      revealed the hypoechoic fascicles of the brachial plexus at the interscalene
      level, the tip of a 22-gauge, 5-cm short-bevel needle was inserted into a
      position adjacent to one of the fascicles by ultrasound guidance. At this point,
      0.1 to 0.2 mL of india ink solution was injected. The brachial plexus at this
      level was then dissected and removed. The nerve elements discolored by the ink
      were removed, fixed, and stained for histologic analysis and were then examined
      for evidence of subepineurial ink deposition. Four nerve segments, which were
      unaffected by the injected ink, served as controls. These were subjected to
      topical india ink application for a 60-min period and were then washed, fixed,
      and stained for histologic analysis. RESULTS: In all 10 interscalene sites,
      ultrasonography revealed multiple hypoechoic nodules that could be traced
      proximally to the spine, as in live subjects. On gross analysis after dissection,
      the superficial nerve elements of the brachial plexus appeared to be stained by
      the ink. On histologic examination, 5 of 10 nerve specimens revealed ink within
      the epineurium (subepineurial), whereas in the other 5, it had not penetrated
      this barrier. The india ink did not penetrate the perineurium in any of the
      specimens. Among control specimens, none had evidence of subepineurial ink.
      CONCLUSIONS: In a cadaver model of needle tip placement for ultrasound-guided
      interscalene block, we found that SEI occurred more frequently than expected.

PMID- 20814288
TI  - "Minor" shoulder surgery--worth a peripheral nerve catheter, or not?

PMID- 20814289
TI  - Pig carcass spine phantom--a model to learn ultrasound-guided neuraxial
      interventions.

PMID- 20814291
TI  - Supraclavicular blocks and phrenic nerve paresis.

PMID- 20814292
TI  - Peripheral nerve blockade may be safer in 2010 than in 2000.

PMID- 20814293
TI  - Is a selective brachial plexus block at the axilla possible when using a nerve
      stimulator and large volumes of local anesthetic?

PMID- 20814294
TI  - Brachial plexus blockade as a result of aberrant anatomy after superficial
      cervical plexus block.

PMID- 20814295
TI  - Electrocardiogram artifact caused by peripheral nerve stimulation during regional
      anesthesia.

PMID- 20814296
TI  - Clinical importance of study results.

PMID- 20814297
TI  - Does a 2-dimensional picture compensate for lacking anatomic knowledge?

PMID- 20814298
TI  - The up-down methodology and practical peripheral nerve blockade.

PMID- 20814299
TI  - Minimum volume, meticulous method.

PMID- 20814301
TI  - Trichosporon surgical wound infection in a renal allograft recipient successfully
      treated with voriconazole.

PMID- 20814302
TI  - Influence of the F12 -4 C>T polymorphism on hemostatic tests.
AB  - The common F12 -4 C>T polymorphism significantly regulates plasma levels of FXII,
      the first element of the intrinsic pathway of coagulation. Due to the robust
      effects that this pathway has on blood coagulation in vitro, the objective of our
      study was to evaluate the influence of this polymorphism on different hemostatic
      tests. We studied 46 hemostatic parameters in 566 participants: 280 patients with
      mucocutaneous bleeding and 286 controls. The F12 -4T allele, associated with
      reduced levels of FXII (P < 0.001), also significantly delayed the activated
      partial thromboplastin time (aPTT) expressed as aPTTr (ratio sample plasma/normal
      pooled plasma). Thus, both patients and controls carrying the T allele had higher
      aPTTr than C/C homozygous individuals (P < 0.001). Interestingly, 92% of healthy
      controls who had prolonged aPTTr carried the F12 -4T allele. Moreover,
      individuals with the F12 -4T allele also had less thrombin generation (assessed
      by endogenous thrombin potential, thrombin peak and time to achieve the peak of
      thrombin) using a test with low tissue factor concentration and explicit contact
      phase activation. Finally, both patients and controls carrying the F12 -4T allele
      also displayed significantly lower FIXc and FVIIc levels than C/C individuals (P
      < 0.01). For all associations except for FVIIc, a gene-dosage effect was
      observed, and homozygous TT individuals had the farthest values. Our study
      reveals a significant effect of the F12 -4 C>T polymorphism on hemostatic tests
      widely used in routine clinical practice.

PMID- 20814303
TI  - Encouraging healthy beverage intake in child care and school settings.
AB  - PURPOSE OF REVIEW: Inappropriate intake of sugar-sweetened beverages, fruit
      juice, and whole milk is associated with obesity and obesity-related
      comorbidities. As numerous children spend many hours in schools and child care,
      these settings provide a potential means for general pediatricians to reach
      children and their parents with interventions to encourage intake of guideline
      recommended beverages. This review describes the beverages currently offered
      within child care facilities and schools and summarizes school and child care
      based interventions and policies to encourage healthy beverage intake. RECENT
      FINDINGS: The major sources of beverages available in schools and child care
      include beverages provided through federal programs, competitive beverages (e.g.,
      beverages for purchase through vending machines), water from drinking fountains,
      and beverages brought into facilities. Policies governing the types of beverages
      available in schools and child care settings have increased, but still vary in
      scope and jurisdiction. Although there are no child care-based interventions that
      exclusively target beverage intake, there are examples of school-based
      interventions to encourage healthy beverage consumption. SUMMARY: Although
      interventions and policies to encourage healthy beverage intake in schools and
      child care are increasing, there is a need for additional research, programs, and
      policies to guide beverage availability and intake in these settings.

PMID- 20814304
TI  - Psychotherapeutic options for traumatized children.
AB  - PURPOSE OF REVIEW: This review addresses two issues. First, it updates readers on
      new treatments for traumatized children. Second, it examines the breadth of
      target problems that current evidence-based treatments for child posttraumatic
      stress disorder (PTSD) effectively address in the context of current diagnostic
      uncertainty. Specifically, changes have been proposed to the Diagnostic and
      Statistical Manual for Mental Disorders Fourth Edition (DSM-IV) diagnostic
      criteria for PTSD and a proposal has been submitted to add a new developmental
      trauma disorder to optimally describe the range of outcomes experienced by
      traumatized children. RECENT FINDINGS: Three recently completed treatment studies
      are described. A review of five established child trauma treatments for PTSD,
      child-parent psychotherapy, cognitive behavioral interventions for trauma in
      schools, cognitive behavioral therapy for PTSD, structured psychotherapy for
      adolescents responding to chronic stress, and trauma-focused cognitive behavioral
      therapy documents that these treatments effectively resolve problems in multiple
      domains beyond the current PTSD diagnostic criteria. These domains include
      affective dysregulation, behavioral dysregulation, cognitive dysregulation, and
      relational dysregulation. SUMMARY: New treatments for children are promising for
      treating PTSD and some other symptoms. Current evidence-based child trauma
      treatments address a broad array of trauma-related difficulties.

PMID- 20814305
TI  - The genetics of obstructive sleep apnoea.
AB  - PURPOSE OF REVIEW: Obstructive sleep apnoea syndrome (OSAS) is a highly prevalent
      disorder associated with reduced quality of life and adverse cardiovascular and
      metabolic sequelae. Recent years have seen an intensification of the research
      effort to establish the genetic contribution to the development of OSAS and its
      sequelae. This review explores emerging evidence in this field. RECENT FINDINGS:
      A genetic basis for sleep-disordered breathing has been demonstrated for discrete
      disorders such as Treacher-Collins and Down syndromes, but the picture is less
      clear in so-called idiopathic OSAS. A degree of heritability appears likely in
      some of the intermediate phenotypes that lead to OSAS, particularly craniofacial
      morphology. However, only sparse and often contradictory evidence exists
      regarding the role of specific polymorphisms in causing OSAS in the general
      population. Similarly, investigations of the cardiovascular sequelae of OSAS have
      in general failed to consistently find single causative genetic mutations.
      Nonetheless, evidence suggests a role for tumour necrosis factor-alpha
      polymorphisms in particular, and large-scale family studies have suggested shared
      pathogenetic pathways for the development of obesity and OSAS. SUMMARY: As with
      other common disorders, OSAS is likely to result from multiple gene-gene
      interactions occurring in a suitable environment. The application of modern
      genetic investigative techniques, such as genome-wide association studies, may
      facilitate new discoveries in this field.

PMID- 20814306
TI  - Aminoglycoside use in cystic fibrosis: therapeutic strategies and toxicity.
AB  - PURPOSE OF REVIEW: This review summarizes the recent literature regarding the
      uses for and toxicity of aminoglycosides in cystic fibrosis (CF). RECENT
      FINDINGS: Aminoglycosides are indicated in the management of acute exacerbations
      of CF, to control chronic infection, and to eradicate Pseudomonas aeruginosa
      after recent acquisition. Intravenous gentamicin is associated with increased
      risk of acute kidney injury, whereas intravenous tobramycin is less so. Studies
      regarding chronic kidney disease related to cumulative aminoglycoside exposure
      are currently conflicting, but a prevalence of up to 42% has been reported. A
      single daily dose of intravenous tobramycin is as effective as a thrice-daily
      regimen and is less nephrotoxic. A large paediatric series has recently reported
      a prevalence of hearing impairment of 4.5%, and a small adult cohort has found a
      30% rate of vestibulotoxicity. Neither appears to be related to cumulative
      exposure. SUMMARY: In recent years, the well known toxicities of aminoglycosides
      have been investigated in CF populations. It appears that intravenous tobramycin
      is well tolerated in the kidneys compared with gentamicin, and that cumulative
      exposure may result in chronic kidney disease. Hearing loss and vestibulotoxicity
      are also prevalent. These important epidemiological studies lay the groundwork to
      design interventional studies to reduce toxicity.

PMID- 20814307
TI  - Prader-Willi syndrome: sorting out the relationships between obesity,
      hypersomnia, and sleep apnea.
AB  - PURPOSE OF REVIEW: Although several studies in the last years have evaluated
      obesity, obstructive sleep apnea (OSAS), and excessive daytime sleepiness (EDS)
      in patients with Prader-Willi syndrome (PWS), their pathophysiologies and
      interactions and the role of treatment with growth hormone are not completely
      understood. The present review analyzes the contributing role of obesity, OSAS,
      and sleep structure abnormalities in determining the EDS and the role of specific
      treatment in improving the clinical outcome. RECENT FINDINGS: The studies on
      sleep structure of PWS patients show abnormalities of rapid eye movement (REM)
      sleep and a decrease in non-REM sleep instability, corroborating the hypothesis
      of the presence of a primary disorder of vigilance and the similarities with
      narcolepsy. These sleep alterations might also be linked to the action of
      mediators of inflammation (i.e. adiponectin or cytokines) determined by obesity.
      Obesity and hypothalamic dysfunction could be responsible for the primary
      abnormalities of ventilation during sleep that, in turn, might contribute to EDS.
      Although EDS seems to resemble narcolepsy, PWS patients do not present the other
      typical symptoms of narcolepsy. SUMMARY: The most consistent hypothesis for
      linking the three different symptoms of PWS is a primary central hypothalamic
      dysfunction. Further research is needed to evaluate the contribution of the upper
      airway resistance syndrome in the pathogenesis of EDS, the role of the
      alterations of sleep microstructure, the relationships between PWS and
      narcoleptic phenotype, the involvement of orexin/hypocretin, and the effects of
      drugs acting on REM sleep and/or wakefulness.

PMID- 20814308
TI  - Emerging issues in cystic fibrosis newborn screening.
AB  - PURPOSE OF REVIEW: There has been a rise in the introduction of cystic fibrosis
      (CF) newborn screening (NBS) programs in recent years. Despite many long running
      and successful programs with established protocols, new strategies are being
      developed in an effort to improve sensitivity and specificity. In light of the
      emerging issues of NBS, new algorithms have been implemented and are reviewed
      here. RECENT FINDINGS: The increase in mixing of populations affects both
      immunoreactive trypsinogen values and sensitivity of genetic analysis in NBS.
      Adjustments to the mutation panel are not always possible. Algorithms adding
      nongenetic tiers may prove to be an alternative. The interpretation of the sweat
      test in neonates has been changing too, and there is now agreement that the upper
      limit of a normal sweat chloride is 29 mmol/l. Infants identified by NBS with a
      sweat chloride of 30-59 mmol/l and no evidence of two CF-causing mutations
      require further evaluation and often a long clinical follow-up before CF may be
      confirmed or excluded. Some NBS programs have reported a steady reduction in the
      incidence of CF, traceable to prenatal diagnosis on subsequent pregnancies and
      population-based carrier screening. SUMMARY: Although there is not one universal
      CF NBS protocol that will suit the heterogeneous needs of diverse regions, many
      options for adjusting algorithms to local conditions are now available.

PMID- 20814309
TI  - Update on cystic fibrosis-related diabetes.
AB  - PURPOSE OF REVIEW: The aim is to provide a detailed review of recent publications
      on cystic fibrosis-related diabetes (CFRD) with a particular focus on the
      interplay between cystic fibrosis (CF) lung disease and diabetes. RECENT
      FINDINGS: CFRD is a form of diabetes that is distinct from type 1 or type 2
      diabetes. CFRD remains very common and increases in prevalence with increasing
      age so that one in two middle-aged CF persons have CFRD. People with CFRD have
      lower lung function, worse nutrition, more frequent hospitalization, and worse
      mortality than CF people without diabetes. The excess mortality previously noted
      in women with CFRD compared with CF women without diabetes or CF men is much less
      apparent. CFRD is due to insulin deficiency and peripheral insulin resistance is
      much less a factor. Genetic susceptibility and oxidant stress are key risk
      factors for developing CFRD. The lung is the prime end organ target in CFRD and
      mortality is due to respiratory failure, not vascular complications. Insulin is
      the mainstay of therapy and early recognition and institution of therapy appear
      to improve health outcomes. SUMMARY: CFRD remains one of the most important co
      morbidities in CF. Early recognition of the disease and therapeutic intervention
      may diminish the negative impact that diabetes has on lung health in CF. Although
      a clearer understanding of the role of oxidant stress and genetics in the
      pathogenesis of CFRD is being elucidated, much needs to be learned before more
      targeted, specific therapies can be developed for this distinct form of diabetes.

PMID- 20814310
TI  - A prediction model for left ventricular mass in patients at high cardiovascular
      risk.
AB  - BACKGROUND: Left ventricular (LV) mass has a continuous relation with
      cardiovascular risk, and regression of LV mass induced by pharmacological
      treatment is associated with improved prognosis. Therefore, early identification
      of patients with a large LV mass is desired. We developed a model to predict LV
      mass in individual hypertensives at high cardiovascular risk. DESIGN AND METHODS:
      We analyzed data of 536 hypertensives with symptomatic extracardiac
      atherosclerotic disease or marked risk factors for atherosclerosis from a cross
      sectional study in a tertiary referral center. LV mass was measured by cardiac
      MRI. We developed the prediction rule with multivariable linear regression
      analysis and stepwise backward elimination. Internal validation was assessed with
      bootstrap sampling to obtain an estimate of model performance (R2) that may be
      expected for new patients. RESULTS: Important predictors for LV mass included
      sex, height, body mass index, systolic blood pressure, and previous aneurysm of
      the abdominal aorta. R2 of the prediction model was 45% after internal
      validation, which was considerably higher than the R2 of previously reported
      models (range 1-38%). Addition of electrocardiography data showed limited
      improvement of the model performance (R2=47%). CONCLUSION: We present a
      prediction model for LV mass in hypertensives at high cardiovascular risk. After
      external validation, this model may be used in clinical practice to estimate LV
      mass for early identification of large LV mass. The predictions of the model may
      support appropriate medical care in the prevention of cardiovascular disease.

PMID- 20814311
TI  - Heart in heart.

PMID- 20814312
TI  - Heart failure and personalized medicine.
AB  - Personalized medicine is a form of medicine that uses the patient's genomic
      information to improve diagnosis, prevention and therapy. In this review we
      discuss the personalized management of heart failure, from monogenic disorders,
      to modifier genes and pharmacogenomics. Monogenic disorders causing heart failure
      are cardiomyopathies. In this disease, recent guidelines assist the clinician in
      molecular diagnostics, genetic counseling and therapeutic choices. Several lines
      of evidence suggest the existence of common polymorphic variants of genes that
      modify the susceptibility to heart failure (modifier genes). A candidate gene
      approach has shown that common genetic variants of the renin-angiotensin
      adrenergic pathway can also influence heart failure and may be associated with
      different outcomes. However, still little is known regarding this and it is
      expected that more advanced high throughput technologies will allow the discovery
      of a number of novel modifier genes that could be used for prognostic profiling
      and development of novel therapeutics. Finally, pharmacogenomics of heart failure
      appears very promising. Common genetic variants of beta-adrenergic receptors,
      alpha-adrenergic receptors and endothelin receptors, among others, significantly
      alter the response to heart failure therapy. This knowledge could be used to
      personalize and optimize heart failure therapy based on the patient's genetic
      profile. Whereas the advances in technologies will continue to transition
      personalized medicine from research to the clinical setting, physicians, and in
      particular cardiologists, need to reshape clinical diagnostics paradigms, learn
      how to use new genomic information to change management decisions, and provide
      the patients with appropriate education and management recommendations.

PMID- 20814313
TI  - Long-term outcomes with cobalt-chromium bare-metal vs. drug-eluting stents: the
      REgistro regionale AngiopLastiche dell'Emilia-Romagna registry.
AB  - OBJECTIVE: To compare the long-term efficacy of cobalt-chromium bare-metal stents
      (CCSs) with that of first-generation drug-eluting stents (DESs) in patients
      within a large real-world multicentre registry. METHODS: The incidence of major
      adverse cardiac events [death, acute myocardial infarction, and target-vessel
      revascularization (TVR)] and angiographic stent thrombosis were assessed in
      consecutive patients undergoing percutaneous coronary intervention with CCS (n =
      1103) or DES (n = 5195) during 2-year follow-up. Propensity score-adjusted
      outcomes, overall and in patients with low (<= 10%), intermediate (10-15%), and
      high (>15%) 1-year restenosis risk, were estimated. RESULTS: DES-treated patients
      had significantly higher rates of diabetes, longer lesions, and smaller vessel
      diameters than CCS-treated patients (all P < 0.0001). However, CCS patients were
      older and presented a higher rate of hypertension, previous myocardial
      infarction, and heart failure (all P < 0.01). At 2 years, adjusted rates of
      myocardial infarction, death, and cumulative-stent thrombosis were similar for
      DES and CCS. DES provided statistically significant (P < 0.01) reductions in TVR
      and adjusted major adverse cardiac event rates (9.7 and 17.2%, respectively)
      compared with CCS (13.2 and 21.2%, respectively). In patients at highest and
      intermediate risk of restenosis, adjusted TVR rates were significantly (P < 0.01)
      lower with DES (12.2 and 8.9%, respectively) than CCS (19.9 and 17.1%,
      respectively), but rates were similar in low-risk patients. CONCLUSION: DESs were
      more effective than CCSs in lowering TVR rates in patients with an intermediate
      high baseline restenosis risk.

PMID- 20814314
TI  - Triage and management of pericardial effusion.
AB  - Pericardial effusion may be detected as an incidental finding during
      echocardiography or following a diagnostic imaging study for a symptomatic
      patient. When a pericardial effusion is detected the first step is to assess its
      size, hemodynamic importance, and possible associated diseases. The more common
      causes of pericardial effusions include infections (viral, bacterial, especially
      tuberculosis), cancer, connective tissue diseases, pericardial injury syndromes,
      metabolic causes (i.e. hypothyroidism), myopericardial and aortic diseases. The
      relative frequency of different causes depends on the local epidemiology, the
      hospital setting and the diagnostic protocol that has been adopted. Many cases
      still remain idiopathic in developed countries, whereas tuberculosis is the
      dominant cause in developing countries. Specific testing should be performed
      according to clinical suspicion. The presence of elevated inflammatory markers
      and other criteria (chest pain, pericardial rubs, ECG changes) suggest
      pericarditis and management should be directed accordingly. Treatment should be
      targeted at the etiology as much as possible. Nevertheless, when diagnosis is
      still unclear, or idiopathic and inflammatory markers are elevated, empiric anti
      inflammatory therapy may be worthwhile. A true isolated effusion may not require
      a specific treatment if the patient is asymptomatic, but large ones have a
      theoretical risk of progression to cardiac tamponade (up to one-third) if
      subacute with signs of right-sided collapse, and especially chronic (>3 months).
      Pericardiocentesis alone may be curative for large effusions but recurrences are
      also common and pericardiectomy or less invasive options (i.e. pericardial
      window) should be considered whenever fluid re-accumulates (especially with
      tamponade), becomes loculated, or biopsy material is required.

PMID- 20814315
TI  - A randomized, double-blind comparison of risperidone versus low-dose risperidone
      plus low-dose haloperidol in treating schizophrenia.
AB  - Monotherapy is recommended for schizophrenia treatment, but the risk-benefit
      issue of antipsychotic drug combination (except for clozapine) remains unclear.
      Risperidone, an atypical antipsychotic drug, has a lower incidence of
      extrapyramidal syndrome but higher risks of prolactinemia and metabolic syndrome
      than haloperidol, a typical agent. This study compared efficacy and safety of
      risperidone monotherapy versus low-dose risperidone plus low-dose haloperidol in
      schizophrenia. In this 6-week, double-blind study, patients were randomized to
      the combination group (2-mg/d risperidone plus 2-mg/d haloperidol, n = 46) or the
      monotherapy group (4-mg/d risperidone, n = 42). Efficacy assessments included
      Clinical Global Impression-Severity, Positive and Negative Syndrome Scale and
      subscales, Calgary Depression Scale, Global Assessment of Functioning, and
      Medical Outcomes Study Short-Form 36. Safety was rigorously monitored. Response
      was defined as 30% reduction in the Positive and Negative Syndrome Scale total
      score. The 2 treatment groups were similar in (1) demographic and clinical
      characteristics at baseline, (2) response rate, and (3) improvement in various
      psychopathological measures and quality of life at end point. The monotherapy
      group had a higher increase in prolactin levels (P = 0.04) and Simpson-Angus
      Scale scores (P = 0.04) and a higher percentage of biperiden use (P = 0.045).
      There were no significant between-group difference in changes in weight, vital
      signs, corrected QT interval, liver/renal function, fasting glucose level, and
      lipid profiles. The findings suggest that risperidone monotherapy may yield
      higher prolactin levels than a combination of low-dose risperidone plus low-dose
      haloperidol. The 2 treatment groups are similar in efficacy, life quality, and
      other safety profiles. Future long-term studies are warranted.

PMID- 20814316
TI  - Quetiapine and norquetiapine in plasma and cerebrospinal fluid of schizophrenic
      patients treated with quetiapine: correlations to clinical outcome and HVA, 5
      HIAA, and MHPG in CSF.
AB  - This study investigated concentrations of quetiapine and norquetiapine in plasma
      and cerebrospinal fluid (CSF) in 22 schizophrenic patients after 4-week treatment
      with quetiapine (600 mg/d), which was preceded by a 3-week washout period. Blood
      and CSF samples were obtained on days 1 and 28, and CSF levels of homovanillic
      acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4
      hydroxyphenylglycol (MHPG) concentrations were measured at baseline and after 4
      weeks of quetiapine, allowing calculations of differences in HVA (DeltaHVA), 5
      HIAA (Delta5-HIAA), and MHPG (DeltaMHPG) concentrations. Patients were assessed
      clinically, using the Positive and Negative Syndrome Scale (PANSS) and Clinical
      Global Impression Scale at baseline and then at weekly intervals. Plasma levels
      of quetiapine and norquetiapine were 1110 +/- 608 and 444 +/- 226 ng/mL, and the
      corresponding CSF levels were 29 +/- 18 and 5 +/- 2 ng/mL, respectively. After
      the treatment, the levels of HVA, 5-HIAA, and MHPG were increased by 33%, 35%,
      and 33%, respectively (P < 0.001). A negative correlation was found between the
      decrease in PANSS positive subscale scores and CSF DeltaHVA (r(rho) = -0.690, P <
      0.01), and the decrease in PANSS negative subscale scores both with CSF Delta5
      HIAA (r(rho) = -0.619, P = 0.02) and DeltaMHPG (r(rho) = -0.484, P = 0.038).
      Because, unfortunately, schizophrenic patients experience relapses even with the
      best available treatments, monitoring of CSF drug and metabolite levels might
      prove to be useful in tailoring individually adjusted treatments.

PMID- 20814317
TI  - A pilot, 8-week, placebo lead-in trial of quetiapine extended release for
      depression in midlife women: impact on mood and menopause-related symptoms.
AB  - Perimenopausal and early postmenopausal women have shown an increased risk for
      developing depression (new onset or recurrent); concomitant vasomotor and other
      menopause-related complaints significantly affect quality of life and overall
      functioning. This study examined the effects of quetiapine extended release (XR)
      in midlife women with major depressive disorder who also reported significant
      menopause-related symptoms. Forty eligible women with major depressive disorder
      entered a 2-week, placebo lead-in phase, followed by an 8-week open trial with
      quetiapine XR, flexible dose, 150-300 mg/d. The primary outcome measure
      (depressive symptoms) was assessed using the Montgomery-Asberg Depression Rating
      Scale (MADRS) scores. Other measures included menopause symptoms (Greene
      Climacteric Scale total scores and subscores) and the impact of hot flashes on
      functioning (Hot Flash-Related Daily Interference Scale). Weight, cholesterol,
      triglycerides, and glucose levels were monitored. Data from 24 subjects (modified
      intent-to-treat, last observation carried forward; quetiapine XR mean dose, 191
      [SD, 55] mg/d) showed improvement in depressive and menopause-related symptoms,
      that is, reduction in MADRS, GCS, and Hot Flash-Related Daily Interference Scale
      scores (P < 0.01 for all comparisons). Seventeen subjects were considered
      responders (>50% reduction in MADRS scores); 15 achieved remission (MADRS<10).
      Main adverse effects included drowsiness and dry mouth. Based on these
      preliminary results, quetiapine XR should be further examined in larger,
      controlled trials for the management of depressed, symptomatic midlife women.

PMID- 20814318
TI  - Esquire trial: efficacy and adverse effects of quetiapine versus risperidone in
      first-episode schizophrenia.
AB  - OBJECTIVE: To compare the efficacy and adverse effect profiles of 2 widely used
      atypical antipsychotics in the short-term phase of first-episode schizophrenia in
      patients who were treatment-naive. A secondary objective was to establish the
      effective dose of these drugs in this context. METHODS: A total of 72 patients
      with a first episode of schizophreniform psychosis (schizophrenia spectrum
      disorder) with less than 2 weeks of exposure to antipsychotic medication were
      randomized to quetiapine or risperidone in a single-blind 12-week controlled
      trial. Psychopathologic diagnoses and adverse effects were assessed by blinded
      raters at 4 weekly intervals. Medication was administered by a specialized
      clinical team following dosing guidelines. Data were analyzed using an intention
      to-treat paradigm. RESULTS: Both quetiapine and risperidone were associated with
      a reduction in immediate symptoms and relatively few adverse effects other than
      weight gain. There was no statistically significant difference between the 2
      compounds in adverse effects, relative efficacies, or adherence to treatment. The
      median (SD) time to cessation for patients randomized to quetiapine was 65.3
      (41.85) days and that for risperidone was 82.5 (44.88) days. There was no
      statistically significant difference between time to discontinuation for the 2
      compounds. The mean daily doses prescribed were 375 mg of quetiapine and 2.72 mg
      of risperidone. CONCLUSIONS: Quetiapine and risperidone are both effective
      treatments in first-episode schizophrenia at doses lower than those used in
      patients with long-term schizophrenia and are similar in efficacy and the
      incidence of adverse effects.

PMID- 20814319
TI  - Treatment options for bipolar depression: a systematic review of randomized,
      controlled trials.
AB  - This meta-analysis examined the effectiveness of treatments of bipolar
      depression. Trials were identified using the MEDLINE, EMBASE,
      http://www.clinicaltrials.gov, and Cochrane databases (1993 to July 2008). The
      outcome measures included mean change in Montgomery-Asberg Depression Rating
      Scale (MADRS) or Hamilton Depression Rating Scale (HAM-D) total scores, and rates
      of response and remission. Overall, 19 publications were included. Medications
      included quetiapine, lamotrigine, paroxetine, lithium, olanzapine, aripiprazole,
      phenelzine, and divalproex. The most trials were identified for quetiapine (5)
      and lamotrigine (6). Not all medications were associated with symptomatic
      improvement (significant reduction in MADRS/HAM-D total scores vs placebo), with
      lamotrigine, paroxetine, aripiprazole, and lithium not being different from
      placebo. Highest reductions in MADRS scores versus placebo were reported for the
      olanzapine-fluoxetine combination (1 trial: -6.6; 95% confidence interval [CI], 
      9.59 to -3.61; P = 0.000) and quetiapine monotherapy (5 trials: for 300 mg/d, 
      4.8; 95% CI, -6.18 to -3.49; P = 0.000; for 600 mg/d, -4.8; 95% CI, -6.22 to 
      3.28; P = 0.000), with quetiapine monotherapy also showing the highest reduction
      in HAM-D scores (4 trials: -4.0; 95% CI, -5.0 to -2.9; P = 0.000). All
      medications except paroxetine, lithium, aripiprazole, and phenelzine
      significantly improved the ratio of probabilities of response (overall rate,
      1.31; 95% CI, 1.22-1.40) and remission (1.32; 95% CI, 1.20-1.45) versus placebo.
      Variability in efficacy exists between treatments of bipolar depression.
      Quetiapine and the olanzapine-fluoxetine combination showed the greatest
      symptomatic improvement. Efficacy considerations will need to be balanced against
      safety and tolerability of the individual agents.

PMID- 20814320
TI  - Incidence of extrapyramidal symptoms and tardive dyskinesia in schizophrenia:
      thirty-six-month results from the European schizophrenia outpatient health
      outcomes study.
AB  - The incidence of treatment-emergent extrapyramidal symptoms (EPSs) and tardive
      dyskinesia (TD) in schizophrenic patients, and the clinical characteristics
      associated with an increased risk of developing EPSs and TD were examined.
      Patients (N = 7728) in the 3-year, prospective, observational Schizophrenia
      Outpatient Health Outcomes study were examined according to baseline
      antipsychotic drug exposure. At baseline, 4893 patients (63.3%) had no EPS, and
      6921 (89.6%) had no TD. Extrapyramidal symptoms and TD were assessed separately
      during follow-up: frequency and time to appearance from Kaplan-Meier survival
      curves and factors associated with time to appearance using Cox proportional
      hazard regression models. The cumulative incidence of EPS ranged from 7.7%
      (olanzapine) to 32.8% (depot typical drugs). Compared with olanzapine, patients
      taking depot typical drugs, oral typical drugs, risperidone, and amisulpride had
      a significantly higher risk of developing EPS. Differences from clozapine were
      marginally significant. High baseline clinical severity was associated with a
      significantly higher risk of developing EPS. The incidence of TD ranged from 2.8%
      (olanzapine) to 11.1% (depot typical agent). Compared with olanzapine, patients
      taking depot typical agents, oral typical agents, and risperidone had a
      significantly higher risk of developing TD. Baseline factors associated with a
      significantly higher risk of developing TD were age, EPS, a higher negative
      Clinical Global Impression score, and presence of gynecomastia. In summary,
      patients treated with typical antipsychotic agents (oral and depot) and
      risperidone had a higher risk of developing EPS and TD than patients treated with
      olanzapine. Higher baseline clinical severity was associated with EPS
      development, whereas age, presence of EPS, a higher negative Clinical Global
      Impression score, and presence of gynecomastia were associated with TD
      development.

PMID- 20814321
TI  - Psychotropic drugs on in vitro brain-derived neurotrophic factor production in
      whole blood cell cultures from healthy subjects.
AB  - The aim of this study was to evaluate the effects of certain antidepressant and
      antipsychotic drugs on the in vitro production of brain-derived neurotrophic
      factor (BDNF) in whole blood cell culture from healthy volunteers. Whole blood
      cells from 41 healthy volunteers were stimulated with or without
      phytohemagglutinin and lipopolysaccharides with treatments of amitriptyline,
      paroxetine, mirtazapine, and venlafaxine, which are antidepressant drugs, and
      haloperidol and clozapine, which are antipsychotic drugs. Brain-derived
      neurotrophic factor levels were measured in supernatants of unstimulated and
      stimulated whole blood cell cultures. When the effects of each antidepressant
      agent at the therapeutic concentration were compared with the effects in control
      subjects using the Wilcoxon test, the in vitro BDNF production was significantly
      enhanced in the stimulated cultures treated with amitriptyline (P = 0.021). When
      analyzing the change in the BDNF productions by each of the drugs using the
      Friedman test, amitriptyline significantly increased the BDNF production in
      stimulated cultures (P = 0.002), whereas paroxetine, mirtazapine, and venlafaxine
      did not stimulate the BDNF production (P > 0.05). However, BDNF production by
      amitriptyline was only increased by 12% to 17%. Haloperidol and clozapine at
      therapeutic concentrations did not significantly alter the BDNF production in
      unstimulated and stimulated whole blood cells (P > 0.05). Our study suggests that
      some antidepressant and antipsychotic agents do not have a direct effect on
      increasing the BDNF production in whole blood cells during immediate treatment.
      Thus, the level of BDNF production in human blood cells may not influence the
      plasma or serum BDNF levels of subjects in clinical studies.

PMID- 20814322
TI  - What is a geriatric psychopharmacologist to do?

PMID- 20814323
TI  - Antipsychotic drug use and the risk of venous thromboembolism in elderly
      patients.
AB  - OBJECTIVE: Our aim was to investigate the relationship between exposure to
      antipsychotic drugs and the risk of venous thromboembolism (VTE) in elderly
      patients. METHODS: A time-matched case-control analysis nested within a cohort of
      111,818 patients with at least 1 antipsychotic drug prescription during 1998 to
      2008. Data were used from the PHARMO institute's database, which contains drug
      dispensing data from community pharmacies and hospital admission data. The index
      date was for the cases defined as the date of hospital admission for VTE (deep
      venous thrombosis [DVT] or pulmonary embolism) or, for outpatient cases, the
      start of therapeutic dose low-molecular weight heparin therapy. For each case, 4
      controls matched by age and sex were randomly sampled from the cohort.
      MEASUREMENTS: Two measures were used to evaluate the temporal relationship
      between antipsychotic drug use and the occurrence of VTE: being a current,
      recent, or past user and the duration of use up to the index date. The strength
      of the association was expressed as odds ratios with 95% confidence intervals,
      taking into account potential confounders. RESULTS: We identified 367 cases of
      hospital admission for DVT, 342 cases of hospital admission for PE, and 323 cases
      of outpatient treatment of DVT. Current exposure to antipsychotic drugs was not
      associated with an increased risk of VTE, compared with nonusers (odds ratio,
      0.9; 95% confidence interval, 0.7-1.1). We found no association between dosage,
      the duration of use, or the type of antipsychotic drug and the risk of VTE.
      CONCLUSIONS: We found no evidence of an increased risk of VTE in elderly patients
      using antipsychotic drugs.

PMID- 20814324
TI  - Acute nicotine alteration of sensory memory impairment in smokers with
      schizophrenia.
AB  - CONTEXT: Patients with schizophrenia have a high rate of cigarette smoking and
      also exhibit profound deficits in sensory processing, which may in part be
      ameliorated by the acute actions of smoke-inhaled nicotine. The mismatch
      negativity (MMN), a preattentive event-related potential index of auditory
      sensory memory, is diminished in schizophrenia. The MMN is increased in healthy
      controls with acute nicotine. OBJECTIVE: To utilize the MMN to compare auditory
      sensory memory in minimally tobacco-deprived (3 hours) patients and matched
      tobacco-deprived smoking controls and to assess the effects of acute nicotine on
      MMN-indexed sensory memory processing in the patients. DESIGN: Event-related
      potentials were recorded in 2 auditory oddball paradigms, one involving tone
      frequency changes (frequency MMN) and one involving tone duration changes
      (duration MMN). Controls were assessed once under nontreatment conditions, and
      patients were assessed twice under randomized double-blind treatment conditions
      involving placebo and nicotine (8 mg) gum. SETTING: Outpatient mental health
      center. PATIENTS: Twelve smokers with schizophrenia and twelve control smokers.
      RESULTS: Compared with the controls, the patients showed reduced frequency-MMN (P
      < 0.001) and duration-MMN (P < 0.04) amplitudes. In addition to prolonging peak
      latency in duration MMN (P < 0.01), nicotine, relative to placebo, increased the
      amplitude of the patients' duration MMN (P < 0.01), but not their frequency MMN,
      to a level comparable with that seen in the controls. CONCLUSIONS: These
      preliminary findings demonstrate for the first time that acute nicotine can
      normalize temporal aspects of sensory memory processing in patients with
      schizophrenia, an effect that may be mediated by activation of alpha7 nicotinic
      acetylcholine receptors, the function of which is diminished in schizophrenia.
      These ameliorating actions of nicotine may have implications for understanding
      the close relationship between tobacco smoking and schizophrenia and for
      developing nicotinic pharmacotherapies to alleviate sensory memory impairments in
      schizophrenia.

PMID- 20814325
TI  - Single- and multiple-dose pharmacokinetics of methylphenidate administered as
      methylphenidate transdermal system or osmotic-release oral system methylphenidate
      to children and adolescents with attention deficit hyperactivity disorder.
AB  - This was a 1-month, multicenter, open-label, randomized study to determine single
      and multiple-dose pharmacokinetics of d,l-methylphenidate (MPH) after MPH
      transdermal system (MTS) and osmotic-release oral system MPH (OROS MPH) dosing in
      children (6-12 years) and adolescents (13-17 years) who had a diagnosis of
      attention deficit hyperactivity disorder. The pharmacokinetic population
      consisted of 33 children and 31 adolescents. Accumulation of d-MPH was 34% in
      children and 57% in adolescents after multiple fixed doses of MTS for 7 days and
      76% and 94%, respectively, after 28 days of dosing. After 7 days of OROS MPH
      dosing, accumulation was 16% in children and 19% in adolescents; fixed doses of
      OROS MPH were not studied beyond 7 days. After escalating the doses to 30 mg per
      9 hours for MTS, accumulation was 73% in children and 83% in adolescents after
      allowing for dose escalation. Corresponding values for OROS MPH after dose
      escalation to 54 mg were 33% in both age groups. Plasma l-MPH concentrations were
      approximately half those of d-MPH for MTS and negligible for OROS MPH. Overall,
      MTS accumulation was above that expected for single-dose pharmacokinetics of MTS
      and OROS MPH in both age groups. As a result of accumulation, systemic exposure
      to d-MPH in children after multiple escalating doses was 1.4- to 1.6-fold higher
      for MTS compared with OROS MPH, but similar in adolescents for both formulations.
      After all dosing, systemic exposure was greater in children compared with
      adolescents, consistent with lower body weight in children. Adverse events were
      mild to moderate for both formulations, and MTS dermal responses were mild.

PMID- 20814326
TI  - Magnitude of rater differences in assessment scales for schizophrenia.
AB  - The magnitude of rater differences, instead of interrater reliability, in the
      assessment scales of schizophrenia has rarely been investigated and was therefore
      addressed in this study. Thirty-six patients with schizophrenia were
      independently assessed by 4 expert physicians, using clinical rating scales
      including the Positive and Negative Syndrome Scale (PANSS). The scores obtained
      by the physician in charge (PIC), who had a long close contact with the patients,
      served as the referent answer for the purpose of this study. The scores rated by
      the other 3 non-PIC psychiatrists, who had a first formal examination with them,
      were evaluated for percentage deviance from the referent answer. The results
      showed that the PIC raters endorsed the numerically highest score in 20 (56%) of
      the 36 patients, whereas they rated the lowest in only 2 (6%) in the PANSS total
      score. The non-PIC assessors on the average underrated the PANSS total score by
      10%, and such a tendency of underestimating the severity was noted across other
      clinical scales. Furthermore, the PANSS total score by one of the non-PIC
      physicians was deviant from the referent answer by at least 20% in 15 (42%) of 36
      instances. Importantly, this magnitude of deviance was noted in the context of an
      intraclass correlation coefficient of 0.92. This unique investigation disclosed
      clinically pertinent differences among raters, even under an excellent interrater
      reliability. The magnitude of differences described herein seems to be an
      underestimation, and the baseline scores by the independent new raters might need
      to be corrected for those by the PICs.

PMID- 20814327
TI  - Prevalence, predictors, and consequences of long-term refusal of antipsychotic
      treatment in first-episode psychosis.
AB  - OBJECTIVE: Studies investigating medication adherence in psychosis are limited by
      the need of a certain degree of medication adherence and the inclusion of mostly
      multiple-episode patients. By contrast, noninformed consent, epidemiological
      studies in first-episode psychosis (FEP) allow the assessment of an important
      subgroup of patients who persistently refuse antipsychotic medication and thereby
      never receive an adequate antipsychotic trial. The present study aims to assess
      the prevalence and predictors of such a "medication refusal" subgroup and its
      association with illness outcome. METHODS: The present file audit study assessed
      medication adherence in an epidemiological cohort of 605 FEP patients who were
      treated within the Early Psychosis Prevention and Intervention Centre for up to
      18 months. Medication adherence was categorized into full adherence,
      nonadherence, and persistent medication refusal. Predictors were analyzed using
      logistic regression models. RESULTS: During the 18-month treatment period, 204
      patients (33.7%) were fully adherent, 287 (47.4%) displayed at least 1 phase of
      nonadherence, and 114 patients (18.8%) were persistent medication refusers. Poor
      premorbid functioning, comorbid substance use, and poor insight predicted both
      medication refusal and nonadherence; a forensic history and no previous contact
      to psychiatric care were specifically predictive of medication refusal. With
      respect to illness outcome, nonadherent patients were worse off when compared
      with fully adherent patients, and medication refusers were even worse off
      compared with nonadherent patients. CONCLUSIONS: Within a nonselected
      epidemiological FEP cohort, almost 20% of patients are persistent medication
      refusers. The found predictors may help to identify the individual risk of
      persistent medication refusal and may enable an early (preventive) treatment
      adaptation.

PMID- 20814328
TI  - C825T polymorphism of the GNB3 gene on valproate-related metabolic abnormalities
      in bipolar disorder patients.
AB  - BACKGROUND: Valproate (VPA) is a mood stabilizer for treating patients with
      bipolar disorder (BD). It may cause metabolic abnormalities in certain bipolar
      patients. However, the genetic factors that influence the susceptibility remain
      unclear. Genetic polymorphism of the G-protein beta3 subunit (GNB3) is reported
      to be associated with metabolic phenotypes. In the current study, we investigated
      the possible associations between the GNB3 variation and VPA-induced metabolic
      abnormalities. METHODS: Subjects (n = 96) who met the Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition criteria for BD were recruited from
      the National Cheng Kung University Hospital. Their metabolic indices were
      measured. RESULTS: The variation of GNB3 C825T showed an association with higher
      plasma total cholesterol (P = 0.037), triglyceride (P = 0.014), and leptin (P <
      0.001) levels in BD patients treated with VPA. After adjusting for age, sex,
      types of BDs, and serum concentration of VPA, the variation of GNB3 C825T
      remained significantly associated with the levels of serum leptin and body mass
      index (BMI; P < 0.001 and P = 0.030, respectively). In addition, the GNB3 C825T
      showed significant drug-single-nucleotide polymorphism interactions with insulin
      levels (P = 0.033), triglyceride levels (P = 0.013), leptin levels (P = 0.013),
      and BMI (P = 0.018). These results indicated that the T allele may be associated
      with lower serum leptin levels and BMI in BD patients treated with VPA.
      CONCLUSIONS: The current study provides evidence that BD patients who are T
      allele carriers of the GNB3 C825T polymorphism have a lower risk for VPA-induced
      metabolic abnormalities. Further studies about the underlying mechanisms of G
      protein in VPA-induced metabolic abnormalities are warranted.

PMID- 20814329
TI  - Clozapine mobilizes CD34+ hematopoietic stem and progenitor cells and increases
      plasma concentration of interleukin 6 in patients with schizophrenia.
AB  - The blood of 8 European patients with schizophrenia without manifest comorbidity
      was studied whether the classical atypical antipsychotic drug clozapine altered
      the amount of circulating CD34(+) hematopoietic cells. As assessed by flow
      cytometry, the number of CD34(+) cells increased by 433% (from 1.49 +/- 1.07 *
      10(6)/L, mean +/- SD pretreatment, to a peak of 6.45 +/- 3.47 * 10(6)/L)
      following first-time therapy with clozapine for 12 weeks. The increase of CD34(+)
      cell, neutrophil, and leukocyte counts was statistically significant (P = 0.012).
      A transversal investigation of 23 long-term patients and 58 controls showed
      elevated neutrophil counts in the clozapine-monotreated group, whereas CD34(+)
      cell numbers were unaltered. A transversal investigation of 12 clozapine
      monotreated long-term patients and 10 controls revealed a 1.3-fold elevation of
      plasma interleukin 6 levels in patients on clozapine (P = 0.017). In conclusion,
      clozapine treatment results in an initial mobilization of CD34(+) stem and
      progenitor cells into the peripheral blood and in a slight long-term elevation of
      interleukin 6.

PMID- 20814330
TI  - Paliperidone extended-release in schizoaffective disorder: a randomized,
      controlled study comparing a flexible dose with placebo in patients treated with
      and without antidepressants and/or mood stabilizers.
AB  - This 6-week, double-blind, placebo-controlled study evaluated paliperidone
      extended-release (ER) as both monotherapy and adjunctive therapy to mood
      stabilizers and/or antidepressants (MS/ADs) for schizoaffective disorder.
      Included subjects had a schizoaffective disorder diagnosis; a Positive and
      Negative Syndrome Scale (PANSS) total score of 60 or higher; a score of 4 or
      higher on 2 or more of the PANSS items for hostility, excitement, tension,
      uncooperativeness, or poor impulse control; and prominent mood symptoms (>=16 on
      the Young Mania Rating Scale and/or the 21-item Hamilton Rating Scale for
      Depression). Subjects were randomized to 6 mg/d paliperidone ER or placebo with
      flexible dosing (3-12 mg/d) until day 15. Randomization was stratified by use of
      MS/AD and study site. The primary analysis outcome was change in PANSS total
      score at week 6 last observation carried forward end point. A total of 311
      subjects received paliperidone ER (n = 216) or placebo (n = 95); 52.0% received
      MS/AD. The mean (SD) modal dose of paliperidone ER was 8.6 (2.5) mg/d. Greater
      improvement was observed with paliperidone ER than placebo on mean (SE) PANSS
      total scores: -20.0 (1.3) and -10.8 (1.9), respectively. Subjects with prominent
      manic or depressive symptoms showed greater improvement with paliperidone ER
      versus placebo: mean (SE) Young Mania Rating Scale (-10.6 [0.9] vs -5.7 [1.2],
      respectively) and 21-item Hamilton Rating Scale for Depression (-10.2 [0.7] vs 
      6.2 [1.1], respectively). The most common adverse events with paliperidone ER
      were headache, akathisia, dizziness, insomnia, and dyspepsia. Paliperidone ER
      improved psychotic and affective symptoms both as monotherapy and as an adjunct
      to MS/AD. No new safety findings were observed in this population.

PMID- 20814331
TI  - Effects of CYP2D6 genotype on the pharmacokinetics, pharmacodynamics, and safety
      of risperidone in healthy volunteers.
AB  - The objective of this study was to analyze the relationship between CYP2D6
      genotype and pharmacokinetics and pharmacodynamics of risperidone. Seventy-one
      healthy volunteers (36 women and 35 men) received a 1-mg single oral dose of
      risperidone. Six major CYP2D6 polymorphisms (CYP2D6*3, *4, *5, *6, *7, and *9)
      and the duplication were detected. Subjects were classified into 4 phenotypic
      groups: 6 ultrarapid (UMs), 34 extensive (EMs), 25 intermediate (IMs), and 6 poor
      metabolizers (PMs). There was a clear relationship between the number of active
      alleles and the pharmacokinetic parameters for risperidone and 9
      hydroxyrisperidone, but there were no differences for total active moiety. Area
      under the curve and half-life of risperidone were significantly higher in PMs and
      IMs compared with EMs and UMs, which showed higher area under the curve of 9
      hydroxyrisperidone. Risperidone produced a small decrease in blood pressure, a
      mild increase in QTc and a quick increase in prolactin, without significant
      differences between groups. Surprisingly, the incidence of adverse reactions was
      lower in PMs (50%) than in other subjects (78%). In conclusion, metabolism of
      risperidone depends on the number of active CYP2D6 alleles. So, PM subjects show
      higher concentrations of risperidone and very low concentrations of 9
      hydroxyrisperidone. On the contrary, EM and UM subjects show low concentrations
      of risperidone and high concentrations of 9-hydroxyrisperidone. However, no major
      pharmacodynamic differences are observed between CYP2D6 genotypes, presumably
      because of the similar pharmacological activity of parent drug and metabolite.

PMID- 20814332
TI  - A randomized, 3-phase, 34-week, double-blind, long-term efficacy study of osmotic
      release oral system-methylphenidate in adults with attention
      deficit/hyperactivity disorder.
AB  - We conducted a 3-phase, double-blind, placebo-controlled, parallel study design
      of osmotic-release oral system (OROS)-methylphenidate (MPH) in adults (19-60
      years of age) with attention deficit/hyperactivity disorder as classified by the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Phase 1 of
      the study was a 6-week, acute efficacy trial (n = 223), phase 2 was a 24-week,
      double-blind continuation study of responders (n = 96), and phase 3 was a double
      blind, placebo-controlled, 4-week discontinuation study (n = 23). The mean daily
      dosage at phase 1 endpoint was 78.4 +/- 31.7 mg (0.97 +/- 0.32 mg/kg) OROS-MPH
      and 96.6 +/- 26.5 mg (1.16 +/- 0.19 mg/kg) placebo (P < 0.0001). Clinical
      response at phase 1 endpoint was significantly greater in the OROS-MPH group
      (62%, n = 67 vs 37%, n = 41; P < 0.001) and was maintained throughout 24 weeks of
      double-blind treatment. With double-blind, placebo-controlled discontinuation,
      however, there was no statistically significant difference in the rate of relapse
      between OROS-MPH responders randomized to placebo and those randomized to
      continue active treatment (18%, n = 2 vs 0%, n = 0; P = 0.1). As expected,
      decreased appetite, insomnia, being tense/jittery, mucosal dryness, and
      neurological symptoms were statistically significantly associated with OROS-MPH
      treatment. More work is needed to be conducted with larger samples being followed
      to study completion to better understand the long-lasting impact of
      pharmacotherapy for adult attention-deficit/hyperactivity disorder.

PMID- 20814333
TI  - Dose-dependent effects of adjunctive treatment with aripiprazole on
      hyperprolactinemia induced by risperidone in female patients with schizophrenia.
AB  - Hyperprolactinemia is a frequent consequence of treatment with risperidone.
      Recent studies have suggested that aripiprazole, a partial dopamine agonist,
      reduces the prolactin response to antipsychotics. Thus, we examined the dose
      effects of adjunctive treatment with aripiprazole on the plasma concentration of
      prolactin in patients who had elevated prolactin levels because of risperidone
      treatment. Aripiprazole was concomitantly administrated to 16 female patients
      with schizophrenia receiving 2 to 15 mg/d of risperidone. Dosages of aripiprazole
      were gradually increased from 3 to 12 mg/d with 2- to 4-week intervals. Sample
      collections for prolactin were conducted before aripiprazole administration
      (baseline) and 2 to 4 weeks after the dose escalation of aripiprazole and just
      before next dose escalation. The samples were taken just before the morning dose.
      The plasma concentration of prolactin during aripiprazole administration (3, 6,
      9, or 12 mg/d) was significantly lower than that at baseline. The mean (+/-SD)
      percent reductions at 3, 6, 9, and 12 mg/d were 35% +/- 14%, 54% +/- 17%, 57% +/-
      19%, and 63% +/- 17%, respectively. However, neither the plasma concentration of
      prolactin nor the reduction ratio differed among the dosages of 6, 9, and 12 mg/d
      of aripiprazole. Three out of 8 patients with amenorrhea improved after 12 mg/d
      of aripiprazole. The present study suggests that adjunctive treatment with
      aripiprazole reduces the prolactin concentration that had been increased because
      of risperidone treatment. The effect occurs even when a low dosage (3 mg/d) of
      aripiprazole was used and achieves a plateau at dosages beyond 6 mg/d.

PMID- 20814334
TI  - Venlafaxine-associated serotonin syndrome causing severe rhabdomyolysis and acute
      renal failure in a patient with idiopathic Parkinson disease.
AB  - A 43-year-old male patient with idiopathic Parkinson disease, on dopaminergic
      therapy, was admitted with confusion and agitation, diaphoresis, and hyperkinesia
      after the commencement of the serotonin-noradrenaline reuptake inhibitor
      venlafaxine 2 weeks prior for depression. He was found to have severe
      rhabdomyolysis and developed acute renal failure. The most likely diagnosis was
      serotonin syndrome induced by venlafaxine, although neuroleptic malignant
      syndrome was also considered. The differential diagnosis, atypical features in
      this presentation, and possible mechanisms are discussed.

PMID- 20814335
TI  - Effects of 2 adenosine antagonists, quercetin and caffeine, on vigilance and
      mood.
AB  - Quercetin, a phenolic flavonoid found in small quantities in some fruits and
      vegetables, is an adenosine receptor antagonist in vitro marketed as a dietary
      supplement for purported caffeine-like effects. A double-blind, placebo
      controlled, between-subjects study was conducted to compare the behavioral
      effects of quercetin to a central adenosine receptor antagonist, caffeine. Fifty
      seven volunteers received either 2000 mg of quercetin dihydrate (a dose estimated
      based on in vitro receptor binding to be equivalent in potency to 200 mg of
      caffeine), placebo, or 200 mg of caffeine. One hour later, a 45-minute visual
      vigilance task was administered. The Profile of Mood States questionnaire was
      completed before treatment and immediately after vigilance testing. On the
      vigilance task, caffeine increased the number of stimuli detected (P < 0.02) and
      decreased the reaction time (P = 0.001). Caffeine increased self-reported vigor
      and reduced fatigue and total mood disturbance Profile of Mood States scores
      compared with placebo. Quercetin did not significantly alter any parameter, but
      values were typically intermediate between caffeine and placebo on those tests
      affected by caffeine. Quercetin is unlikely to have any effects when consumed by
      humans in quantities present in the diet or in dietary supplements. Caffeine (200
      mg) administration resulted in the expected effects on vigilance and mood.

PMID- 20814336
TI  - Antidepressant pharmacotherapy failure and response to subsequent
      electroconvulsive therapy: a meta-analysis.
AB  - Failure to respond to antidepressants probably is the most common indication for
      electroconvulsive therapy (ECT). The literature seems to be divided as to whether
      medication resistance has a negative influence on the efficacy of subsequent ECT.
      Therefore, we performed a systematic review to investigate the effect of previous
      pharmacotherapy failure on the efficacy of ECT. Relevant cohort studies were
      identified from systematic search of the PubMed electronic database. Seven
      studies were included in this meta-analysis: the overall remission rate amounts
      to 48.0% (281/585) for patients with and 64.9% (242/373) for patients without
      previous pharmacotherapy failure. An exact analysis with the Mantel-Haenszel
      method (fixed effect model) shows a reduced efficacy of ECT in patients that
      received previous pharmacotherapy (OR, 0.52; 95% confidence interval [CI], 0.39
      0.69). In conclusion, the efficacy of ECT is significantly superior in patients
      without previous pharmacotherapy failure as compared with medication-resistant
      patients. Because this finding is based on observational studies, it might be
      caused by a confounding factor, for example, the presence of psychotic features
      or the duration of the index episode. Electroconvulsive therapy seems to be an
      effective treatment for severely depressed patients as well as for patients with
      previous pharmacotherapy failure.

PMID- 20814337
TI  - A pilot study comparing traumatic stress symptoms by child and parent report
      across pediatric chronic illness groups.
AB  - OBJECTIVE: Researchers have recently used a framework of traumatic stress to
      describe the psychological functioning of children experiencing a chronic illness
      and their families; however, few studies are available directly comparing
      symptoms across disease groups. This study compared traumatic stress symptoms of
      youth being considered for solid organ and bone marrow transplantation, youth
      diagnosed with human immunodeficiency virus, youth diagnosed with sickle cell
      disease and their parents. Correlates of traumatic stress across these
      populations were also examined. METHOD: Participants included 64 youth and
      caregiver dyads with previously scheduled appointments at 1 of 3 specialty
      clinics. Parents completed measures of family demographics, traumatic stress
      symptoms, and child functional status. Youth (n = 45) and parents each completed
      self-report and parent-proxy measures of youth traumatic stress symptoms.
      RESULTS: Ten percent of youth by self-report, 18% of youth by parent-proxy
      report, and 13% of caregivers described symptoms suggestive of posttraumatic
      stress disorder. Parents of pediatric transplant self-reported greater symptoms
      than caregivers of youth with human immunodeficiency virus and sickle cell
      disease (p < .05). Although child functional impairment did not predict child
      symptoms, a trend was found where parents experiencing more traumatic stress
      symptoms themselves reported their children experienced greater symptoms by
      parent-proxy report (p =.07). CONCLUSION: Findings suggest that although most
      children and parents across disease groups report subclinical levels of traumatic
      stress symptoms, traumatic stress symptoms may be especially salient for families
      of pediatric transplant candidates. Although interventions are currently
      available to treat posttraumatic stress disorder symptoms, they will likely need
      to be individualized to meet the needs of specific disease groups.

PMID- 20814338
TI  - Evaluation of a brief parenting discussion group for parents of young children.
AB  - OBJECTIVE: Although behavioral parenting programs are effective at treating child
      behavioral problems, a significant number of parents experiencing these problems
      do not receive help, and briefer, more cost-effective parenting interventions are
      lacking. This study aimed to evaluate the efficacy of a brief parenting
      discussion group. METHOD: Sixty-seven parents were randomly assigned to either an
      intervention or waitlist control condition. Parents in the intervention condition
      took part in a 2-hour discussion group in which they were taught positive
      parenting strategies to prevent and manage their child's disobedience, and they
      received 2 follow-up telephone calls after the discussion group. RESULTS: Results
      showed that after intervention, there were reductions in child behavior problems
      and use of dysfunctional parenting and improvements in parental self-efficacy and
      the parenting experience for parents. These effects were maintained at 6-month
      follow-up. CONCLUSION: The results are promising because they show that a brief
      intervention can be minimally sufficient to improve child and parent outcomes for
      parents experiencing high levels of child behavior problems.

PMID- 20814339
TI  - Course of depressive symptoms in overweight youth participating in a lifestyle
      intervention: associations with weight reduction.
AB  - OBJECTIVE: The study investigates whether preintervention depressive symptoms
      predict weight loss and whether an increase in depressive symptoms during a group
      based lifestyle intervention of 1 year's duration is associated with failure in
      weight reduction while controlling for the influence of psychosocial risks.
      METHOD: Participants were 136 overweight and obese children and adolescents
      between 7 and 15 years, who had been referred for weight reduction treatment by
      local pediatric practices. Depressive symptoms in the child/adolescent were
      screened by a German version of the Children's Depression Inventory, in
      accordance with DSM-IV criteria, at baseline and conclusion of the program.
      Family adversity was assessed using the Psychosocial Risk Index at baseline.
      Preintervention maternal depression was assessed using the Center for
      Epidemiological Studies Depression Scale. RESULTS: Preintervention depressive
      symptoms in the child/adolescent did not predict reduction in body mass index
      standard deviation score. High number of psychosocial risks predicted an increase
      in depressive symptoms. Independently of this association, failure to reduce
      weight within the 1-year duration of the program was significantly associated
      with an increase in depressive symptoms. CONCLUSION: It is necessary to identify
      cases at risk to offer further and more specific support.

PMID- 20814342
TI  - Introduction: Reports from the 12th Symposium on Cochlear Implants in Children.

PMID- 20814340
TI  - Associations between sleep and inattentive/hyperactive problem behavior among
      foster and community children.
AB  - OBJECTIVE: Sleep disruption has been linked to numerous neural regulatory
      problems and problems with social emotional and behavioral functioning, and
      researchers have shown that sleep disruption is prominent in children with
      symptoms of attention-deficit hyperactivity disorder. These issues are germane to
      foster children, who have numerous disparities in areas of self-regulation and
      psychopathology but for whom there has been very little examination of sleep
      quality or the associations between poor sleep quality and
      physiological/behavioral dysregulation. METHOD: Actigraphy measures were used to
      examine associations between sleep duration/quality and inattentive/hyperactive
      problem behavior in a sample of 79 children (aged 5-7 years): 32 foster children
      and 47 nonmaltreated community children. RESULTS: Of the sleep variables
      examined, only sleep duration was significantly associated with
      inattentive/hyperactive problem behavior. These associations were more
      significant in foster children compared to community children and in boys
      compared to girls. CONCLUSION: The results have several implications for
      prevention and intervention research.

PMID- 20814343
TI  - Speech perception in congenitally deaf children receiving cochlear implants in
      the first year of life.
AB  - OBJECTIVE: To investigate whether children implanted in the first year of life
      show higher levels of speech perception than later-implanted children, when
      compared at the same ages and to investigate the time course of sensitive periods
      for developing speech perception skills. More specifically, to determine whether
      faster gains in speech perception are made by children implanted before 1 year
      old relative to those implanted at 2 or 3 years. STUDY DESIGN: Retrospective
      cohort study. SETTING: Tertiary academic referral center. PATIENTS: 117 children
      with congenital profound bilateral sensorineural hearing loss, with no additional
      identified disabilities. INTERVENTION: Cochlear implantation in the first,
      second, or third year of life. MAIN OUTCOME MEASURE: Development curves showing
      Lexical Neighborhood Test (LNT) word identification scores as a function of age.
      RESULTS: Children implanted within the first year of life have a mean advantage
      of 8.2% LNT-easy word scores over those implanted in the second year (p < 0.001)
      and a 16.8% advantage in LNT-easy word scores over those implanted in the third
      year of life (p < 0.001). These advantages remained statistically significant
      after accounting for sex, residual hearing, and bilateral cochlear implant use.
      When speech perception scores were expressed as a function of "hearing age"
      rather than chronological age, however, there were no significant differences
      among the 3 groups. CONCLUSION: There is a clear speech perception advantage for
      earlier-implanted children over later-implanted children when compared at the
      same age but not when compared at the same time after implantation. Thus, the
      sensitive period for developing word identification seems to extend at least
      until age 3 years.

PMID- 20814344
TI  - Cochlear implants in otosclerosis.

PMID- 20814345
TI  - Force of cochlear implant electrode insertion performed by a robotic insertion
      tool: comparison of traditional versus Advance Off-Stylet techniques.
AB  - OBJECTIVE: Robotic cochlear implant electrode array insertion offers substantial
      potential advantages, namely repeatability and minimization of insertion forces,
      leading to decreased intracochlear trauma. Using such a robotic insertion tool,
      we sought to analyze force profiles during deployment of stylet-containing
      electrode arrays using either traditional insertion, in which the stylet is
      withdrawn after complete insertion of the electrode, or Advance Off-Stylet (AOS)
      insertion, in which the stylet is withdrawn simultaneous with electrode array
      insertion. STUDY DESIGN: Prospective. SETTING: Tertiary referral center.
      INTERVENTIONS: A robotic cochlear implant insertion tool coupled with a force
      sensing carriage was used to perform electrode array insertions into an
      anatomically correct, three-dimensional scala tympani model during either
      straight insertion (n = 4) or AOS insertion (n = 4). MAIN OUTCOME MEASURES: Both
      insertion techniques begin with a 7-mm straight insertion during which forces
      were similar averaging approximately 0.006 N. For insertion from 7 to 17 mm,
      traditional insertion forces averaged 0.046 +/- 0.027 N, with a peak of 0.093 N,
      and AOS insertion forces averaged 0.008 +/- 0.006 N, with a peak of 0.034 N.
      Beyond 9.74 mm, the difference between traditional and AOS insertion forces was
      highly significant. CONCLUSION: With the use of a robotic insertion tool, which
      minimizes operator variability and maximizes repeatability, we have shown that
      cochlear implant electrode insertion via AOS is associated with lower average and
      maximum insertion forces compared with traditional insertion. These findings
      support the use of AOS over traditional, straight insertion.

PMID- 20814346
TI  - Dutch Cochlear Implant Group (CI-ON) consensus protocol on postmeningitis hearing
      evaluation and treatment.
AB  - OBJECTIVE: One of the most devastating sequelae of bacterial meningitis is
      profound hearing loss or even deafness. Although cochlear implantation is able to
      restore (some) hearing abilities, obliteration due to fibrosis and especially
      calcification of the cochlea in the postmeningitis period is limiting the success
      rate of an implantation. A national consensus assembled in a postmeningitis
      follow-up protocol has to increase awareness and thus the chances of an early
      detection and possible intervention when profound hearing loss occurs. SETTING:
      All cochlear implant (CI) centers of The Netherlands located in the 8 academic
      otorhinolaryngology and audiology departments of The Netherlands, gathered in the
      Dutch Cochlear Implant Group (CI-ON, Cochlear Implant Overleg Nederland).
      INTERVENTION: A protocol proposed by 3 centers was sent to all other CI centers
      in The Netherlands to review and agree on. MAIN OUTCOME MEASURES: The CI centers
      agreed on the need for, and use of, the proposed protocol. Keystones of the
      protocol are treatment with dexamethasone before start of antibiotics, early
      magnetic resonance imaging and repeated audiological follow-up, and urgent
      referral to a CI center in all cases with greater than 30 dB SNHL. CONCLUSION:
      The Cochlear Implant Centers in The Netherlands (CI-ON) have agreed on a
      protocolized follow-up after bacterial meningitis to increase the chances of an
      early detection and possible intervention should profound hearing loss occur.

PMID- 20814347
TI  - Effective gas exchange in paralyzed juvenile rabbits using simple, inexpensive
      respiratory support devices.
AB  - We have developed two devices: a high-amplitude bubble continuous positive airway
      pressure (HAB-CPAP) and an inexpensive bubble intermittent mandatory ventilator
      (B-IMV) to test the hypotheses that simple, inexpensive devices can provide gas
      exchange similar to that of bubble CPAP (B-CPAP) and conventional mechanical
      ventilation (CMV). Twelve paralyzed juvenile rabbits were intubated, stabilized
      on CMV, and then switched to CPAP. On identical mean airway pressures (MAPs),
      animals were unable to maintain pulse oximeter oxygen saturation (SpO2) >80% on
      conventional B-CPAP, but all animals oxygenated well (97.3 +/- 2.1%) on HAB-CPAP.
      In fact, arterial partial pressures of O2 (Pao2) were higher during HAB-CPAP than
      during CMV (p = 0.01). After repeated lung lavages, arterial partial pressures of
      CO2 (Paco2) were lower with B-IMV than with CMV (p < 0.0001), despite identical
      ventilator settings. In lavaged animals, when HAB-CPAP was compared with CMV at
      the same MAP and 100% O2, no differences were observed in Pao2, but Paco2 levels
      were higher with HAB-CPAP (70 +/- 7 versus 50 +/- 5 mm Hg; p < 0.05). Arterial
      blood pressures were not impaired by HAB-CPAP or B-IMV. The results confirm that
      simple inexpensive devices can provide respiratory support in the face of severe
      lung disease and could extend the use of respiratory support for preterm infants
      into severely resource-limited settings.

PMID- 20814348
TI  - Urinary excretion of vitamin K metabolites in term and preterm infants:
      relationship to vitamin K status and prophylaxis.
AB  - Little is known about the metabolic turnover and excretion of vitamin K in
      healthy newborn infants and the metabolic consequences of prophylactic regimens
      designed to protect against vitamin K deficiency bleeding (VKDB). We measured the
      excretion of two urinary metabolites (<= 24 h) of vitamin K (5C- and 7C
      aglycones) in term infants before (n = 11) and after (n = 5) a 1000 MUg i.m. dose
      of vitamin K1 (K1) and in preterm infants after 200 MUg i.m. (n = 4), 500 MUg
      i.m. (n = 4), or 200 MUg i.v. (n = 5). In preterm infants, we also measured serum
      K1, vitamin K1 2,3-epoxide, and PIVKA-II at 5 d postpartum. Before prophylaxis,
      the rate of 5C- and 7C-aglycone excretion was 25 times lower than adults,
      reflecting low vitamin K stores at birth. After prophylaxis, the excretion rate
      correlated to K1 dose (r = 0.6) but was two orders of magnitude lower than that
      in adults, probably reflecting the immaturity of neonatal catabolism. All term
      and 10 of 13 preterm infants mainly excreted 5C-aglycone. We present evidence
      that increased excretion of the 7C-aglycone was associated with metabolic
      overload because of the exposure to high-tissue K1 concentrations. Measurement of
      the 5C- and 7C-aglycones may facilitate longitudinal studies of vitamin K status
      in neonates and aid the development of improved prophylactic regimens.

PMID- 20814349
TI  - Analytical toxicology of emerging drugs of abuse.
AB  - The emergence of ever new drugs of abuse on the illicit drug market is an ongoing
      challenge for analytical toxicologists. Because most of these new drugs or drug
      classes are not detected by established analytical methods targeting classic
      drugs of abuse, analytical procedures must be adapted or new procedures must be
      developed to cover these new compounds. This review summarizes the analytical
      toxicology of the following classes of emerging drugs of abuse: piperazines,
      phenethylamines (2Cs and FLYs), 4-substituted amphetamines, beta-keto
      amphetamines, 2,5-dimethoxy-amphetamines, pyrrolidinophenones, and synthetic
      cannabinoids.

PMID- 20814350
TI  - Pharmacokinetics of cocaine and metabolites in human oral fluid and correlation
      with plasma concentrations after controlled administration.
AB  - Oral fluid is an attractive alternative matrix for drug testing with a
      noninvasive and directly observed collection, but there are few controlled
      cocaine administration studies to guide interpretation. MATERIALS AND METHODS:
      While residing on a closed research unit for up to 10 weeks under constant
      medical supervision, 19 participants were administered 75 mg/70 kg subcutaneous
      cocaine and 14 received 150 mg/70 kg. The disposition of cocaine, benzoylecgonine
      (BE), and ecgonine methyl ester (EME) into oral fluid was determined by gas
      chromatography-mass spectrometry for 0.08 to 48 hours after administration.
      RESULTS: In oral fluid collected by citric acid candy-stimulated expectoration,
      cocaine first appeared in oral fluid 0.08 to 0.32 hours after dosing and was
      rapidly eliminated with half-lives of 1.1 to 3.8 hours. BE and EME were first
      detected 0.08 to 1.0 hours after dosing with longer half-lives of 3.4 to 13.8
      (BE) and 2.4 to 15.5 hours (EME) (P < 0.05). Oral fluid and plasma concentrations
      were significantly correlated for cocaine, BE, and EME (P < 0.0001). There were
      no significant differences (P > 0.05) in first and last detection times with the
      8-MUg/L cutoff proposed by the Substance Abuse and Mental Health Services
      Administration or the 10-MUg/L cutoff from the European initiative, Driving Under
      the Influence of Drugs, Alcohol and Medicines. Metabolite:cocaine ratios
      increased after cocaine administration, potentially helpful for interpreting time
      of last use. Comparison of oral fluid collection through citric acid candy
      stimulated expectoration, citric acid-treated Salivette, and neutral cotton
      Salivette devices did not reveal significant differences between devices for
      areas under the curve for cocaine, BE, or EME (P > 0.05). DISCUSSION AND
      CONCLUSION: These results provide additional evidence for interpreting cocaine
      and metabolite concentrations in oral fluid and oral fluid's usefulness as an
      alternative matrix for drug testing.

PMID- 20814351
TI  - Establishment of high-performance liquid chromatography and enzyme multiplied
      immunoassay technology methods for determination of free mycophenolic acid and
      its application in Chinese liver transplant recipients.
AB  - The objective of this study is to investigate the correlation between methods of
      high-performance liquid chromatography (HPLC) and enzyme multiplied immunoassay
      technology (EMIT) for determination of total mycophenolic acid (tMPA) and free
      (fMPA) concentration and to study pharmacokinetics of fMPA in Chinese liver
      transplant recipients. An HPLC method with fluorometric detection and an EMIT
      assay were established to determine fMPA in plasma ultrafiltrates.
      Pharmacokinetic parameters of tMPA and fMPA in 51 patients were estimated. The
      calibration range of fMPA was 0.0025 to 1.0 MUg/mL for the HPLC method and 0.0050
      to 0.50 MUg/mL for the EMIT method. Mean recovery of the two methods was 98.0%
      and 97.1%, respectively. The intraday and interday coefficient of variations were
      0.93% to 3.1% and 1.6% to 2.9% for HPLC and 4.51% to 15.8% and 5.83% to 19.5% for
      EMIT, respectively. The relationship of the two methods was EMIT = 1.074 * HPLC +
      0.582 (r2 = 0.918, n = 470, P < 0.05) for tMPA and EMIT = 1.068 * HPLC + 0.004
      (r2 = 0.945, n = 297, P < 0.05) for fMPA. There was a positive mean bias of EMIT
      for tMPA (27.0%) and fMPA (23.3%). The AUC0-12 of tMPA and fMPA obtained by HPLC
      in 51 patients was 34.7 +/- 11.1 and 0.72 +/- 0.38 MUg.h/mL, respectively. The
      free fraction of MPA was 1.60 +/- 1.21% (Median:1.36%, interquartile: 0.72,
      2.22), [corrected] which was significantly correlated with 7-O-glucuronide
      conjugate of MPA AUC0-12 (r2 = 0.705, P < 0.001), albumin (r2 = -0.529, P <
      0.001), and the clearance of creatinine (r2 = -0.417, r2 = 0.005). Both HPLC and
      EMIT assay are suitable for the determination of fMPA. A considerable
      interindividual variability exists in pharmacokinetics of fMPA among Chinese
      liver transplant recipients. 7-O-Glucuronide conjugate of MPA and albumin
      concentrations are two factors correlated to fMPA variance.

PMID- 20814352
TI  - Biomarkers as a tool for management of immunosuppression in transplant patients.
AB  - Therapeutic drug monitoring is a well-established approach in transplantation
      medicine to guide immunosuppressive therapy. However, it cannot always predict
      the effects of immunosuppressive drugs on immune cells, because it does not
      reflect any aspect of an individual patient's immune system. Pharmacodynamic
      monitoring is a more recent strategy to provide information about the biologic
      effect of a specific drug or drug combination on the individual transplant
      patient. Currently, there is a large number of different biomarkers that either
      directly (specific markers) or indirectly (global markers) relate to the
      pharmacodynamic effects of immunosuppressive drugs and are under investigation as
      potential candidates to be introduced in clinical practice. Such biomarkers may
      be useful to identify patients at risk of developing acute rejection, infection,
      or cancer as well as patients who are suitable for minimization of
      immunosuppressant therapy and may be helpful to manage the timing and rate of
      immunosuppressant weaning. Serial longitudinal monitoring may allow maintenance
      of an individualized immunosuppressive regimen. Thus, biomarker monitoring is a
      potential complementary tool to therapeutic drug monitoring. This review
      summarizes the current state of knowledge about the use of a number of global or
      drug-specific pharmacodynamic biomarkers. It is not a comprehensive overview of
      the literature available, but rather an evidence-based reflection by experts who
      are intensively involved in scientific work in this field.

PMID- 20814353
TI  - Intermediate-term outcomes associated with kidney transplantation in recipients
      80 years and older: an analysis of the OPTN/UNOS database.
AB  - BACKGROUND: An increasing number of patients 80 years and older have received a
      kidney transplant in the United States, but their outcomes are not well
      described. Using Organ Procurement and Transplantation Network/United Network of
      Organ Sharing data, outcomes of recipients 80 years and older were evaluated.
      METHODS: Thirty-one thousand one hundred seventy-nine elderly recipients defined
      by age 60 years and older receiving kidney transplants from 2000 to 2008 were
      stratified: ages 60 to 69 years (n=24,877), 70 to 79 years (n=6,103), and 80
      years and older (n=199). Cox regression models were used to compare patient,
      graft, and death-censored graft survival. RESULTS: The majority of recipients 80
      years and older was male (82.9%), white (87.9%), and less likely to have diabetes
      or coronary artery disease. More expanded criteria donor (ECD) but fewer living
      donor transplants were performed among 80 years and older compared with those
      younger than 80 years. Perioperative mortality, defined as death within 30 days
      posttransplant, was rare (60-69 years: 1.4%; 70-79 years: 1.5%; and >=80 years:
      2.5%) but tended to be higher among those 80 years and older compared with
      recipients 60 to 69 years (hazard ratio [HR] 1.67; 95% confidence interval [CI]
      0.69-4.05). At 2 years, survival was lower for 80 years and older (73%; HR 2.42;
      95% CI 1.91-3.06) and 70 to 79 years (86%; HR: 1.42; 95% CI: 1.34-1.51) compared
      with recipients 60 to 69 years (89%). There was a greater risk of graft loss
      among recipients 80 years and older compared with those 60 to 69 years (HR 1.78;
      95% CI 1.42-2.23); however, no difference in death-censored graft survival was
      observed (0.89; 0.57-1.39). Among recipients 80 years and older, no difference in
      survival was observed between standard criteria donor and ECD recipients.
      CONCLUSION: Although perioperative mortality was uncommon among elderly
      recipients (1.5%), a trend toward higher perioperative mortality was observed in
      recipients 80 years and older. There was no difference in survival among standard
      criteria donor and ECD recipients.

PMID- 20814354
TI  - Granulocyte colony-stimulating factor induced acute and chronic graft-versus-host
      disease.
AB  - BACKGROUND: A recent experimental study in mice shed new light on the controversy
      as to whether granulocyte colony-stimulating factor (G-CSF) increases graft
      versus-host disease (GVHD). Total body irradiation and bone marrow were found to
      be prerequisites for acute GVHD. This study encouraged us to perform a
      retrospective clinical study. METHODS: We compared 260 patients given G-CSF
      prophylaxis after allogeneic hematopoietic stem-cell transplantation with 205
      controls transplanted between 1993 and 2003. RESULTS: G-CSF hastened the
      engraftment of neutrophils, but that of platelets was delayed (P<0.0001). The
      proportion of acute GVHD of grades II to IV was 29% in the G-CSF group and 19% in
      the controls (P<0.01) and that of chronic GVHD was 54% and 43%, respectively
      (P=0.019). G-CSF increased acute and chronic GVHD in patients preferentially
      conditioned with chemotherapy. Unexpectedly, it exacerbated acute GVHD in
      recipients of peripheral blood stem cells and enhanced chronic GVHD in bone
      marrow recipients. A multivariable analysis showed that acute GVHD (hazards
      ratio=1.52, P=0.03) and chronic GVHD (hazards ratio=1.51, P=0.004) were
      associated with G-CSF. There was no significant difference between study groups
      regarding nonrelapse mortality, relapse, or survival. CONCLUSION: G-CSF increased
      acute and chronic GVHD in patients treated with chemotherapy but did not affect
      relapse or survival.

PMID- 20814355
TI  - Pandemic (H1N1) 2009 infection in adult solid organ transplant recipients in
      Singapore.
AB  - BACKGROUND: Influenza can produce significant complications in immunocompromised
      persons. METHODS: We studied the effects of the pandemic (H1N1) 2009 (pH1N1)
      infection on solid organ transplant recipients in our hospital, with emphasis on
      clinical information, duration of viral culture positivity, polymerase chain
      reaction positivity, effects of oseltamivir therapy, and graft status at 6 months
      of follow-up. RESULTS: Twenty-two cases of pH1N1 infection involving 18 renal,
      two lung, one heart, and one liver transplant recipients were seen from July 14
      to September 8, 2009. Their median age was 50.5 years (range 20-70 years); 64%
      were women, and median time posttransplant was 40 months (range 6-204 months).
      Common symptoms were fever (86%), cough (77%), sore throat (55%), phlegm (32%),
      and myalgia (27%). The median duration of symptoms (n=21) and duration of
      polymerase chain reaction positivity (n=15) were 7 (range 4-13 days) and 8 days
      (range 4-16 days), respectively. Mean (+/- SD) duration of symptom resolution
      (7.4 +/- 3.0 vs. 7.8 +/- 3.0 days, P=0.76) and viral culture positivity (5.3 +/-
      2.8 vs. 4.3 +/- 3.2 days, P=0.65) did not differ between those who received a 5
      day (n=9) or 10-day (n=12) course of oseltamivir. Five patients (22.7%) developed
      pneumonia with three needing intensive care. Mortality rate was 4.5% (1/22). At 6
      months, three graft rejections involving two renal and one lung developed.
      CONCLUSIONS: Our findings indicate that the pH1N1 infection in solid organ
      transplant recipients is associated with some degree of morbidity and may affect
      the function of the transplanted organ. In this nonrandomized comparison,
      patients treated with 5 days of oseltamivir did not fare worse compared with
      those who received 10 days.

PMID- 20814357
TI  - [Radiological demography].

PMID- 20814356
TI  - Expression of soluble HLA-G identifies favorable outcomes in liver transplant
      recipients.
AB  - BACKGROUND: Human leukocyte antigen (HLA)-G displays immunotolerogenic properties
      toward the main effector cells involved in graft rejection through inhibition of
      natural killer cell- and cytotoxic T-lymphocyte-mediated cytolysis, and CD4 T
      cell alloproliferation. An increase in serum and graft levels of HLA-G has been
      noted in transplant patients with improved allograft survival. However, the
      clinical relevance of soluble serum HLA-G molecules in tolerant pediatric and
      young adult liver transplant patients remains to be studied. METHODS: We examined
      the serum HLA-G levels in 42 pediatric and young adult liver transplant patients
      with a mean age of 15 years; 13 patients had operational tolerance (TOL), with
      complete immunosuppression withdrawal for 2.3 to 13.2 years. RESULTS: Median HLA
      G level in patients with acute rejection (AR) was similar to the level in
      pediatric healthy volunteers (9.9 vs. 4.2 U/mL, P=0.13). HLA-G was higher in
      patients with stable liver function on immunosuppression (54.6 U/mL) than in
      patients with AR (P=0.01) and healthy volunteers (P=0.003), but almost 6-fold
      lower than in TOL patients (325.4 U/mL). HLA-G did not correlate with clinical
      confounders or a history of posttransplant lymphoproliferative disease or Epstein
      Barr virus; although levels in the TOL group were negatively correlated with time
      after immunosuppression withdrawal (r=-0.75, P=0.003). In rejectors, HLA-G levels
      trended to negatively correlate with a higher number (r=-0.58) and greater
      severity of AR episodes (r=-0.56) after 1 year posttransplantation. CONCLUSIONS:
      Increased serum HLA-G levels track with operational tolerance of liver grafts and
      support favorable outcomes in pediatric and young adult recipients.

PMID- 20814358
TI  - [Mechanisms of delayed myocardial enhancement and value of MR and CT contrast
      materials in the evaluation of myocardial viability].
AB  - The purpose of this article is to present a brief theoretical review of the
      models characterizing delayed myocardial enhancement applicable to both MR and CT
      imaging, review the different characteristics of commercially available
      gadolinium-based and iodinated contrast materials, and summarize the literature
      on the potential value of dedicated MR imaging contrast currently in development
      for the diagnosis of myocardial viability. The intensity of myocardial
      enhancement following infarction is related to two factors: expansion of the
      interstitial volume (15+/-2% in normal myocardium and 80+/-3% within necrosis)
      secondary to cell necrosis and perfusion abnormalities due to the absence of
      revascularization or lesions to the microcirculation. A kinetic model of contrast
      material properties within myocardium could be constructed from Kety's equation
      with regards to enhancement within the different myocardial tissues (viable
      myocardium, necrotic myocardium, fibrosis, no-reflow zones, stunned or
      hibernating myocardium). This model can be applied to both CT and MR since
      clinically available contrast agents are extracellular, inert and kinetically
      comparable. The development of dedicated contrast agents for viability and
      necrosis or molecular contrast agents open new horizons for preclinical research.

PMID- 20814360
TI  - [Left and right ventricular volumetry and ejection fraction with MRI:
      segmentation criteria and interobserver reproducibility].
AB  - PURPOSE: To propose and validate anatomical criteria for the manual segmentation
      of right and left ventricles on cardiac MRI, to evaluate the interobserver
      reproducibility and tho evaluate the ease of implementation. MATERIALS AND
      METHODS: Criteria for the segmentation and the choice of the basal slices were
      defined based on a review of the literature and cardiac anatomy. Cardiac
      volumetric measurements obtained from 20 consecutive patients using these
      criteria were compared to measurements obtained in reference to the orthogonal
      planes, and to those obtained with the classical criteria described in the
      literature. The interobserver reproducibility was statistically assessed for 6
      observers (3 experts and 3 residents with no experience in cardiac imaging). The
      ease of implementation was determined by the post-processing time. RESULTS: Using
      orthogonal planes as a reference, the new criteria for the selection of the basal
      slice resulted in improved interobserver agreement and correlation compared to
      the classical criteria. Interobserver agreement was excellent (intra-class
      coefficient>0.93 for the left ventricle,>0.86 for the right ventricle). The mean
      post-processing time was similar or inferior to results from the literature.
      CONCLUSION: The proposed criteria allow easy volumetric assessment of both
      ventricles, while providing reproducible measurements.

PMID- 20814359
TI  - [Liver calcifications in adults: the KUB stars are too frequently neglected in
      the CT era].
AB  - Liver calcifications have been extensively described on plain radiographs, either
      from KUB or angiography examinations. On the other hand, their characteristics
      are seldom reported on cross-sectional imaging: they are frequently considered as
      non-specific compared to multiple other imaging features. However, clinical
      practice demonstrates that in specific situations (such as parasitic infections
      and calcified metastases), the presence of calcifications may be a determining
      factor in avoiding misdiagnosis with potential deleterious effects to the
      patient. Both CT and US can detect a large number of "benign" calcifications
      without associated focal lesion and knowledge of their imaging features is useful
      to avoid unnecessary additional imaging work-up. A review of the literature and a
      series of 100 cases of liver calcifications on CT are presented to review the
      imaging features of calcified liver lesions and isolated liver calcifications
      without associated focal lesion.

PMID- 20814361
TI  - [Dose reduction at CT of the lumbar spine using a 320-detector row scanner:
      initial results].
AB  - PURPOSE: To compare radiation dose and image quality for CT of the lumbar spine
      between helical CT and wide volume mode scanning with a 320-detector row CT.
      PATIENTS AND METHODS: Monocenter prospective study on 20 consecutive patients
      divided into two groups. All 20 patients underwent lumbar spine CT on the 320
      detector row scanner (Aquilion One, Toshiba). The CT examinations for group 1
      were performed using the wide volume mode with 320 detector rows while the CT
      examinations for group 2 were performed using a 64-detector row helical CT mode.
      The acquisition length and delivered dose corresponding to the DLPe (extended
      dose length product) as well as qualitative and quantitative image quality were
      compared between both groups. RESULTS: The mean acquisition length was comparable
      between both groups. There was a significant dose reduction of about 35% for
      group 1 compared to group 2 (mean DLPe of 970 mGy.cm for group 1 compared to 1503
      mGy.cm for group 2, p<0.028) when using the wide volume mode acquisition at 320
      detector row CT compared to the 64-detector row helical CT mode. No significant
      difference was noted for image quality between both groups. CONCLUSION: The
      acquisition of lumbar CT using the wide volume mode at 320-detector row CT allows
      significant dose reduction to patients compared to the 64-detector row helical CT
      mode while preserving image quality.

PMID- 20814362
TI  - [Venous infarction of the neonate].
AB  - PURPOSE: To determine the imaging features of hemorrhagic infarction in neonates.
      PATIENTS AND METHODS: Retrospective study (1998-2008) of 19 children (17
      premature and 2 term deliveries) with early lobar hyperechogenicity on
      transfontanel US (TFUS). Group I: 11 born infants with clinical as well as TFUS
      and MRI follow-up. Group II: 8 premature infants deceased within a week from
      multisystem pathology, with neuropathological study available in 3 cases.
      RESULTS: Group I (n=11): periventricular hyperechogenicity in a frontal (7),
      frontoparietal (2), parietooccipital (1) and temporoparietal (1) distribution
      with developing cavitary change (n=6). MRI showed a cortex sparing
      intraparenchymal hematoma. Group II (n=8): periventricular hyperechogenicity in a
      frontal (4), frontoparietal or parietal (3) and occipital (1) with developing
      cavitary change (3). Neuropathological examination showed characteristic lesions
      of venous hemorrhagic infarction. Clinical outcome was generally favorable for
      the surviving infants with contralateral motor deficit (n=5) non-correlated to
      the extent of the initial lesions. CONCLUSION: Venous hemorrhagic infarction
      mainly affetcs premature infants and typically involves the periventricular
      frontal white matter. Prognosis is generally favorable. It is thus important to
      differentiate this entity from asymmetrical cystic periventricular leukomalacia
      with much different prognosis.

PMID- 20814363
TI  - [Hydatid cyst of the pancreas presenting with acute pancreatitis].

PMID- 20814364
TI  - [Von Recklinghausen disease presenting with rectal bleeding].

PMID- 20814365
TI  - [Erdheim-Chester disease with mesenteric involvement].

PMID- 20814366
TI  - [Pseudoaneurysm of the breast following percutaneous biopsy].

PMID- 20814367
TI  - [Hepatitis C virus infection revealed by an acute acalculous cholecystitis].

PMID- 20814368
TI  - [Scoliosis, Chiari I and syringomyelia: a triad to never forget].

PMID- 20814369
TI  - [State of the art: interventional radiology management of renovascular
      hypertension].
AB  - The management of renal artery stenosis (RAS) has been the subject of numerous
      clinical studies and recommendations, most frequently with regards to
      atherosclerotic RAS. We present the current recommendations from the French
      Society of Cardiac and Vascular Imaging updated from a recent literature review
      (April 2008) with regards to medical, endovascular and surgical management of
      atheroscletotic and non-atherosclerotic RAS. The evidence-based recommendations
      are ranked by level.

PMID- 20814370
TI  - [Answer to June e-quid de June. Inverted Meckel's diverticulum].

PMID- 20814372
TI  - [Characterization of a cluster of microcalcifications on digital mammography:
      back to basic concepts].

PMID- 20814373
TI  - [Infrapatellar fat pad: anterior crossroads of the knee].
AB  - The infrapatellar fat pad or Hoffa's fat pad is a cylindrical extrasynovial
      collection of fat located in the infrapatellar region. Anatomical, biomechanical
      and imaging data show that the infrapatellar fat pad constitutes a true
      crossroads between patella, femur and tibia and helps in understanding if not
      describing regional pathology. Intrinsic lesions (with abnormal signal on MRI)
      such as hoffitis, anterolateral impingement, plica syndrome, post-arthroscopic
      changes, trauma, patellar dislocation and extrasynovial tumors are less frequent.
      On the other hand, extrinsic lesions are more frequent and may affect the
      synovium, patellar ligament, vascular structures, and bursae. Mucoid and
      parameniscal cysts may develop in the infrapatellar fat pad. In this article, the
      anatomical and imaging features of the infrapatellar fat pad will be summarized
      and the most common lesions will be illustrated.

PMID- 20814374
TI  - [Cardiac tumors: CT and MR imaging features].
AB  - The CT and MR imaging features of the main cardiac tumors will be reviewed. Cross
      sectional imaging features may help differentiate between cardiac tumors and
      pseudotumoral lesions and identify malignant features. Based on clinical
      features, imaging findings are helpful to further characterize the nature of the
      lesion. CT and MR imaging can demonstrate the relationship of the tumor with
      adjacent anatomical structures and are invaluable in the presurgical work-up and
      postsurgical follow-up.

PMID- 20814375
TI  - [Comparison between electronic zoom and geometric magnification of clusters of
      microcalcifications on digital mammography].
AB  - PURPOSE: With the advent of digital mammography with electronic zoom
      capabilities, we have sought to determine the need for geometric magnification
      for the evaluation of clusters of microcalcifications. PATIENTS AND METHODS:
      Eighty-eight clusters of microcalcifications were reviewed by two experienced
      radiologists using electronic zoom (ZOOM) and geometric magnification (MAG). The
      following criteria were evaluated: image quality, shape and number of
      microcalcifications, size and shape of the clusters. The clusters were classified
      based on malignancy risk using the BI-RADS criteria. Histological results from
      macrobiopsy or surgery as well as 2 year follow-up were used as reference for
      statistical analysis. RESULTS: Sensitivity (100% for MAG and 90% for ZOOM),
      specificity (52% versus 39%), positive predictive value (51% versus 44%) and
      negative predictive value (100% versus 88%) were superior for geometric
      magnification compared to electronic zoom irrespective of the reviewer but
      without reaching statistical significance. However, image quality was
      significantly superior with geometric magnification (p<<0.05). In addition,
      reviewers were more confident in their interpretation of geometric magnification
      images. CONCLUSION: Geometric magnification remains necessary in routine clinical
      practice for the characterization of microcalcifications and BI-RADS
      classification.

PMID- 20814376
TI  - [Thermal ablation: tolerance and efficacy in a population mostly composed of
      primary lung cancers].
AB  - PURPOSE: Radiofrequency thermal ablation (TA) of lung tumors currently is
      considered an alternative to surgical management for early primary lung cancers
      and non-surgical lung metastases. The purpose of this study was to determine the
      tolerability and efficacy of this treatment in 29 consecutive patients, most of
      which with primary lung cancers, managed in our center. MATERIALS AND METHODS:
      Twenty-nine patients with 32 lung tumors less than 35 mm in diameter underwent
      radiofrequency thermal ablation between May 2004 and July 2008. The CT
      examinations performed during and after the ablation were reviewed to determine
      lesion characteristics, complications, treatment, local recurrence rate and
      survival rate. RESULTS: Sixty-nine percent of our population consisted of primary
      lung cancer. The incidence of pneumothorax was 72% with 10% requiring drainage.
      The rate of complete response was 81%. The survival rate at 1 year was 79%.
      CONCLUSION: Radiofrequency thermal ablation of lung tumors is a minimally
      invasive technique with high rate of complete response. It can be considered in
      non-surgical patients with primary or metastatic lung tumors less than 35 mm in
      diameter.

PMID- 20814378
TI  - [Transabdominal percutaneous embolization of a type 2B endoleak in a patient with
      covered abdominal aortic endoprosthesis].

PMID- 20814377
TI  - [Embolization of intracranial aneurysms: reimbursement and perspectives].
AB  - PURPOSE: To determine the costs related to the embolization of intracranial
      aneurysms compared to "rates per activity" (T2A) reimbursements. MATERIALS AND
      METHODS: The hospital admissions of patients with intracranial aneurysms treated
      with embolization and classified under diagnosis-related group (DRG) 01K02Z in
      2007 were included. The costs related to the single-use devices,
      neurointerventional suite and hospital stay were calculated by analytical
      accounting. Revenues were calculated based on DRG-based medical information
      system (PMSI) and medical data using the diagnosis-related groups and
      reimbursements from 2007 (V10 of DRG) and 2009 (V11). RESULTS: Fifty-seven
      patients were included. The total cost was 932.278 euro and hospital revenues
      were 655.648 euro in 2007 and would have been 825.211 euro in 2009. The financial
      loss was on average 4.853 euro per admission in 2007 and 1.878 euro in 2009, and
      even more in two cases of ruptured aneurysm. CONCLUSION: In 2001, embolization of
      intracranial aneurysms, the treatment of choice for this pathology, results in a
      financial loss for the hospital, larger for ruptured aneurysms compared to non
      ruptured aneurysms. The updated DRG, while improving the situation, remains
      insufficient.

PMID- 20814379
TI  - [Life-threatening hemoretroperitoneum after percutaneous radiofrequency ablation
      of a renal tumor: treatment by emergency transcatheter arterial embolization].

PMID- 20814380
TI  - [Generalized cystic lymphangiomatosis of bone with splenic involvement: minor
      variant of a systemic disease].

PMID- 20814381
TI  - [Embolization of a Rasmussen's aneurysm complicating active tuberculosis].

PMID- 20814382
TI  - [Common mesentery presenting with left-sided perforated appendicitis].

PMID- 20814384
TI  - [Answer to July-August e-quid. Breast filariasis].

PMID- 20814383
TI  - [Multiple ovarian fibromas in a patient with Gorlin syndrome: US and MR imaging
      features with pathological correlation].
AB  - We report a case of multiple ovarian fibromas in a 23 year old woman with Gorlin
      syndrome. We describe the US and MR imaging features with pathological
      correlation. The fibrous component of the tumors were hypoechoic and attenuating
      on US with corresponding T2W hypointensity whereas myxoid components were
      hypoechoic with increased through transmission on US with corresponding T2W
      hyperintensity.

PMID- 20814386
TI  - [From bone marrow to spinal cord].

PMID- 20814387
TI  - [MR imaging patterns of bone marrow].
AB  - The marrow contains a variable amount of yellow or fatty marrow and red or
      cellular marrow creating the signal intensity observed on MRI. Marrow replacement
      (by cells not normally present in bone marrow) typically is T1W hypointense.
      Marrow proliferation (by cells normally present in bone marrow) may be T1W
      hypointense (pseudo marrow replacement) or show intermediate T1W signal intensity
      due to red marrow redistribution. Marrow edema (reaction to an external process)
      show intermediate T1W hypointensity (mixture of water and marrow). Location will
      allow correct diagnosis. Bone marrow ischemia usually results in a necrotic
      fragment surrounded by a thin T1W hypointense rim.

PMID- 20814388
TI  - [The spinal canal: from imaging anatomy to diagnosis].
AB  - The spinal canal is divided into epidural, subdural and subarachnoid spaces.
      Intraspinal processes should be correctly placed into their space of origin. MRI
      is the best imaging modality to achieve this task. Accurate determination of the
      space of origin routinely requires the acquisition of two different pulse
      sequences, typically T1W and T2W images, in two orthogonal planes, usually axial
      and sagittal. Simple imaging features can assist in determining the site of
      origin: changes to the epidural fat, compression or widening of subarachnoid
      spaces. The epidural space, bordered medially by dura, contains fat and vascular
      structures. The subdural space is a virtual space in between the dura and
      arachnoid membrane. The subarachnoid space is home to the CSF, spinal cord and
      nerve rootlets. An epidural process replaces the epidural fat, displaces the dura
      and narrows the subarachnoid space. A subarachnoid process widens the
      subarachnoid space and spares the epidural fat. Epidural processes usually are
      infectious or tumoral, either primary or secondary to spinal involvement.
      Subarachnoid processes include primary tumors, leptomeningeal metastases,
      arachnoiditis and hemorrhage. Nerve sheath tumors and meningiomas are the most
      frequent intradural extramedullary tumors.

PMID- 20814389
TI  - [Imaging of non-traumatic and non-tumoral cord lesions].
AB  - There is a wide range of spinal cord pathologies (vascular, inflammatory,
      infectious, metabolic, degenerative). They present clinically as acute partial or
      complete cord syndromes, or chronic myelopathies (more than 4 weeks in duration).
      MRI examination should be undertaken with a very strict protocol. Spinal cord
      lesions should be evaluated with regards to their T1W and T2W signal
      characteristics, involvement of grey and/or white matter, axial and sagittal
      extension, cord volume changes, contrast uptake and associated lesions
      (perimedullary, radicular or brain). The correlation of MR imaging features with
      clinical and biological data (blood and CSF) should suggest a differential
      diagnosis.

PMID- 20814390
TI  - [Intramedullary tumours and pseudotumours].
AB  - Swelling of the spinal cord and/or enhancement after intravenous gadolinium
      administration are not always specific features of intramedullary tumour. These
      may also be seen in association with several diseases of inflammatory,
      infectious, granulomatous or vascular origin. A tumour is characterized by its
      sagittal location, axial topography: central, lateral or exophytic, its size and
      size of the spinal canal, macroscopic components: calcium, fat, methemoglobin,
      melanin, hemosiderin, vascular pedicle, cystic component, enhancement after
      intravenous gadolinium administration, effect on the spinal cord tracts and
      edema. Characteristics: astrocytoma is lateral and infiltrative, ependymoma is
      central with white matter tract displacement and hemosiderin cap,
      hemangioblastoma is postero-lateral and shows enhancement with a vascular
      pedicle, metastases are very edematous or leptomeningeal in location.

PMID- 20814391
TI  - [Imaging of acute spinal injury].
AB  - The mechanism location and type of injury varies according to patient age and
      severity of trauma. The imaging work-up with radiographs, CT and MRI must be
      adapted to each individual case. In the setting of minor trauma, standard
      radiographs are obtained when clinically indicated. In all other cases of high
      energy trauma, spinal trauma with neurological deficit or incomplete or difficult
      standard radiographic evaluation, CT will be indicated for osseous injuries while
      MRI will provide optimal evaluation of soft tissues. Dislocations require
      immediate treatment. The imaging work-up should by no means delay management.
      Significant sprains are rare. Several diagnostic pitfalls occur at both
      extremities of life.

PMID- 20814392
TI  - [Traumatic cord and nerve root injuries: imaging features at the acute and
      chronic phases].
AB  - Cord injuries are frequent and severe lesions resulting in significant
      disability, most frequently in younger subjects. The area of cord injured results
      in clinical syndromes (Brown-Sequard, motor and/or sensory deficit...). Cord and
      rootlet injuries are best depicted on MRI. Diffusion tensor imaging with
      tractography enables depiction of the most severe cord lesions and some
      prediction of tissue viability which may provide an idea of the potential
      functional prognosis and patient recovery. MRI is optimal to demonstrate areas of
      cord hemorrhage or compression, partial or complete cord transsection, nerve root
      avulsion...

PMID- 20814393
TI  - [Imaging of the postsurgical spine].
AB  - Some early complications (hematoma, spondylodiscitis, pseudomeningocele) can
      occur with all types of surgery while late complications vary with the type of
      surgery. After discectomy, postsurgical changes (osseous and ligamentous defects,
      scar tissue, granulation tissue) should be distinguished from postsurgical
      complications or recurrent disease (recurrent disc herniation, arachnoiditis,
      spondylodiscitis). Following spinal decompression and fusion procedures, standard
      radiographs and CT can confirm the adequate position of the fusion devices, the
      presence of fusion, and the development of late osseous complications:
      pseudarthrosis, instability and recurrent stenosis.

PMID- 20814394
TI  - [Imaging of the fused spine].
AB  - Imaging interpretation of the fused spine requires adequate knowledge of
      instrumentation and fusion techniques. Familiarity with the normal imaging
      features is needed in order to detect complications. While such complications are
      relatively rare, their presence is clinically significant and may lead to repeat
      surgery. Mechanical complications related to instrumentation and fusion (improper
      device placement, pseudarthrosis, progression of disease at the adjacent non
      fused segments) are distinguished from non-mechanical complications (infection,
      postoperative hematoma, pseudo-meningocele) that usually occur sooner. The
      different complications will be illustrated with focus on the optimal imaging
      work-up (radiographs, CT, MRI).

PMID- 20814395
TI  - [Spinal infections: typical and atypical imaging features].
AB  - While the imaging features of established spondylodiscitis are well known, other
      presentations may be misleading. The purpose of this article is to review the
      typical imaging features of spondylodiscitis as well as some more atypical and
      unusual imaging features (early spondylodiscitis, sceptic spondylitis, septic
      arthritis of facet joints, primary epidural abscess, unusual germs, neonate).

PMID- 20814396
TI  - [Spondyloarthropathy: MR imaging features].
AB  - The new diagnostic criteria for ankylosing spondylitis include MRI. MRI
      frequently allows early diagnosis of inflammatory lesions in patients with normal
      plain films. In addition, MRI is useful for the detection and quantification of
      inflammatory and structural lesions, and to assess disease activity.

PMID- 20814397
TI  - [Vertebral involvement in SAPHO syndrome].
AB  - SAPHO syndrome (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis) is
      characterized by a great variety of radiographic findings, including sclerosing
      osteitis, ivory vertebra, hyperostosis with paravertebral ossification,
      spondylodiscitis and even vertebral compression fractures. On the other hand, the
      MR imaging features are quite stereotypical with presence of entesopathy at the
      anterior vertebral corner similar to other spondyloarthropathies. In about 15% of
      cases, the entesophytes are limited to the anterior vertebral corner. In all
      other cases, it extends to involve the adjacent vertebral endplate, the anterior
      vertebral cortex or the adjacent vertebral corner through the disc annulus. As
      such, involvement of at least two adjacent vertebrae is present in about 30% of
      cases. The intervertebral disc may be narrowed, and, in 10% of cases, show
      intense T2W signal and postcontrast enhancement, simulating infections
      spondylodiscitis. The pseudo-infectious appearance is further increased in about
      one third of cases by the presence of an enhancing mass in the adjacent soft
      tissues. Therefore, these lesions may sometimes be difficult to differentiate
      from infectious spondylodiscitis and even tumors. An important differential
      diagnostic feature is the presence of lesions of varying ages on adjacent
      vertebral segments, with presence of characteristic entesopathy of a vertebral
      corner.

PMID- 20814398
TI  - [Lumbar epidural and foraminal injections: update].
AB  - A fluoroscopy-guided lumbar spine injection procedure may be complicated by
      immediate paralysis. Twelve cases (five recent and seven published) that occurred
      between 2002 and 2008 were reviewed (history of lumbar surgery, route of
      injection, image-guidance, injection of contrast, type of steroid, level of
      paraplegia, MR imaging features). MRI showed cord ischemia from arterial origin.
      The high number of patients with prior lumbar spine surgery suggests that the
      presence of scar tissue could increase the risk of paraplegia. A transforaminal
      approach was used in all patients without history of lumbar surgery while
      transforaminal, interlaminar and juxta-zygapophyseal approaches were used in
      patients with prior lumbar surgery. The high number of cases in France could be
      explained by the exclusive use of prednisolone acetate which has a higher rate of
      macro-aggregate formation that could lead to embolization in medullary arteries.

PMID- 20814399
TI  - [Lumbar transforaminal epidural injections: evaluation of potential risks and
      complications].

PMID- 20814400
TI  - New treatments for metastic prostate cancer.
AB  - The FDA has approved 2 new treatments for castration-resistant (formerly called
      hormone-refractory) prostate cancer. Sipuleucel-T (Provenge - Dendreon) s the
      first immunotherapy approved for treatment of prostate cancer. Cabazitaxel
      (Jevtana - Sanofi-Aventis) is approved for second-line treatment of metastatic
      castration-resistant prostate cancer previously treated with docetaxel
      (Taxotere).

PMID- 20814401
TI  - In brief: propoxyphene toxicity.

PMID- 20814402
TI  - Tribenzor for hypertension.
AB  - Many patients with hypertension require more than one drug to control their blood
      pressure.1 Tribenzor (Daiichi Sankyo), recently approved by the FDA for treatment
      of hypertension, combines the calcium channel blocker amlodipine (Norvasc, and
      others), the angiotensin receptor blocker (ARB) olmesartan (Benicar) and the most
      commonly prescribed diuretic, hydrochlorothiazide (HCTZ). Tribenzor is not
      approved for initial therapy, but is recommended for patients not adequately
      controlled on any 2-drug combination of a calcium channel blocker, an ARB or a
      diuretic.

PMID- 20814403
TI  - Natazia--a new oral contraceptive.

PMID- 20814404
TI  - Multiple-serotype Salmonella gastroenteritis outbreak after a reception ---
      Connecticut, 2009.
AB  - In September 2009, the Connecticut Department of Public Health (DPH) identified
      an outbreak of Salmonella gastroenteritis among attendees at a reception. A case
      control study and environmental and laboratory investigations were conducted.
      Nine case-patients and 14 control subjects were identified. Potato salad
      consumption was strongly associated with illness (odds ratio [OR] = 84.0). During
      the investigation, food service workers were observed to have bare-handed contact
      with ready-to-eat food. Five case-patients and one asymptomatic food service
      worker had stool samples positive for Salmonella species. Two Salmonella
      serotypes were identified, Salmonella enterica serovar Schwarzengrund and
      Salmonella enterica serovar Typhimurium variant O:5--, including coinfection in
      one case-patient and one food service worker. The isolates of each respective
      serotype (S. Schwarzengrund and S. Typhimurium variant O:5--) had
      indistinguishable pulsed-field gel electrophoresis (PFGE) patterns. Potato salad
      was the likely source of the outbreak but the contamination mechanism is unclear.
      Control measures included exclusion of the food service worker with Salmonella
      positive stool from the restaurant until two consecutive stool samples yielded no
      bacterial growth. Standard public health laboratory practices in Connecticut and
      testing techniques used specifically during this investigation led to the rapid
      identification of the two serotypes. Multiple-serotype Salmonella outbreaks might
      occur more frequently than recognized; knowledge of all Salmonella serotypes
      involved in an outbreak might help implicate the outbreak source, define the
      scope of the outbreak, and determine the selection of appropriate control
      measures.

PMID- 20814405
TI  - Use of a self-assessment questionnaire for food safety education in the home
      kitchen --- Los Angeles County, California, 2006-2008.
AB  - Foodborne diseases remain an important cause of morbidity in the United States
      among all age groups. A potentially important contributor to this morbidity is
      improper food handling and preparation practices in kitchens at restaurants and
      in private homes. In 1998, the Los Angeles County Department of Public Health
      (LACDPH) established numeric scores for restaurant inspections and posted grades
      for these inspections publicly; by the end of 1998 this initiative was credited
      with helping to reduce by 13.1% (compared with 1997) the number of
      hospitalizations for foodborne infections from nontyphoidal Salmonella,
      Campylobacter, and Escherichia coli in the region. In the spring of 2006, the
      LACDPH Environmental Health Program launched the Home Kitchen Self-Inspection
      Program, a voluntary self-inspection and education program, to promote safer food
      hygiene practices at home. This report describes the implementation of this
      program and the results from its web-based self-assessment questionnaire, the
      Food Safety Quiz, for the initial program period of 2006--2008. Overall,
      approximately 13,000 adults completed the quiz; 34% received an A rating, 27% a
      B, 25% a C, and 14% received a numeric score because they scored lower than 70%
      on the self-assessment. Use of interactive, online learning tools such as the
      Food Safety Quiz can be used to promote home food safety in the community.
      Further research is needed to evaluate and improve the program content and to
      assess its effect on changing food handling and preparation practices in the home
      kitchen.

PMID- 20814406
TI  - Updated recommendations for prevention of invasive pneumococcal disease among
      adults using the 23-valent pneumococcal polysaccharide vaccine (PPSV23).
AB  - Invasive disease from Streptococcus pneumoniae (pneumococcus) is a major cause of
      illness and death in the United States, with an estimated 43,500 cases and 5,000
      deaths among persons of all ages in 2009. This report provides updated
      recommendations from the Advisory Committee on Immunization Practices (ACIP) for
      prevention of invasive pneumococcal disease (IPD) (i.e., bacteremia, meningitis,
      or infection of other normally sterile sites) through use of the 23-valent
      pneumococcal polysaccharide vaccine (PPSV23) among all adults aged >or=65 years
      and those adults aged 19-64 years with underlying medical conditions that put
      them at greater risk for serious pneumococcal infection. The new recommendations
      include the following changes from 1997 ACIP recommendations: 1) the indications
      for which PPSV23 vaccination is recommended now include smoking and asthma, and
      2) routine use of PPSV23 is no longer recommended for Alaska Natives or American
      Indians aged <65 years unless they have medical or other indications for PPSV23.
      ACIP recommendations for revaccination with PPSV23 among the adult patient groups
      at greatest risk for IPD (i.e., persons with functional or anatomic asplenia and
      persons with immunocompromising conditions) remain unchanged. ACIP
      recommendations for prevention of pneumococcal disease among infants and youths
      aged <or=18 years using the 13-valent pneumococcal conjugate vaccine (PCV13) and
      PPSV23 are published separately.

PMID- 20814407
TI  - Human dopamine beta-hydroxylase promoter variant alters transcription in
      chromaffin cells, enzyme secretion, and blood pressure.
AB  - BACKGROUND: Dopamine beta-hydroxylase (DBH) plays an indispensable role in
      catecholamine synthesis by converting dopamine into norepinephrine. Here, we
      characterized a DBH promoter polymorphism (C-2073T; rs1989787; minor allele
      frequency ~16%) that influences not only gene transcription but also enzyme
      secretion and blood pressure (BP) in vivo. METHODS: Plasma DBH activity was
      measured spectrophotometrically. DBH genetic effects on BP were tested in
      subjects with the most extreme BP values in a large primary care population.
      Functional effects of promoter variants were studied by site-directed mutagenesis
      in DBH promoter haplotype/luciferase reporter plasmids transfected into
      chromaffin cells. Sequence motifs were predicted from position weight matrices,
      and endogenous transcription factor binding was probed by Chromatin
      ImmunoPrecipitation (ChIP). RESULTS: The T-allele of common promoter variant C
      2073T was contained in a promoter haplotype that associated with plasma DBH
      activity, a trait also predicted by that variant itself. Promoter haplotypes
      including C-2073T predicted BP in the population, and the effect was also
      referable to C-2073T itself. Computationally, C-2073 disrupted a predicted match
      for transcription factor c-FOS. Site-directed mutagenesis at C-2073T altered not
      only basal promoter activity, but also transactivation by c-FOS, as well as the
      chromaffin cell secretory stimuli nicotine or pituitary adenylate cyclase
      activating polypeptide (PACAP). Endogenous c-FOS bound to the motif in chromatin.
      CONCLUSIONS: These results suggest that DBH promoter variant C-2073T is
      functional in vivo: this promoter variant seems to initiate a cascade of
      transcriptional and biochemical changes including augmented DBH secretion,
      eventuating in elevation of basal BP, and hence cardiovascular risk. The
      observations suggest new strategies for probing the pathophysiology, risk, and
      treatment of hypertension.

PMID- 20814408
TI  - Morbidity and mortality of orthostatic hypotension: implications for management
      of cardiovascular disease.
AB  - Orthostatic hypotension (OH) is the failure of cardiovascular reflexes to
      maintain blood pressure on standing from a supine or sitting position. Although
      OH may cause symptoms of dizziness or syncope, asymptomatic OH (AOH) is far more
      common and is an independent risk factor for mortality and cardiovascular disease
      (CVD). The prevalence of AOH increases with age, the presence of hypertension or
      diabetes and the use of antihypertensive or other medications. The implications
      of AOH for the treatment of CVD and hypertension are not well defined. This
      review provides an overview of the current information on this topic and
      recommends the more frequent assessment of OH in clinical practice and in future
      clinical trials.

PMID- 20814409
TI  - Higher blood pressure is associated with higher handgrip strength in the oldest
      old.
AB  - BACKGROUND: Aging is associated with progressive loss of muscle strength. Muscle
      tissue is vascularized by an elaborate vascular network. There is evidence that
      blood pressure (BP) is associated with muscle function in middle age. It is
      unknown how BP associates with muscle function in oldest old people. We studied
      the association between BP and handgrip strength in middle and old age. METHOD:
      BP was measured automatically in middle-aged subjects and with a mercury
      sphygmomanometer in the oldest old. Handgrip strength was measured with a
      handgrip strength dynamometer. Cross-sectional measurements of handgrip strength
      and BP were available for 670 middle-aged subjects (mean 63.2 +/- 6.6 years) and
      550 oldest old subjects (all 85 years). Prospective data were available for
      oldest old subjects only with a 4-year follow-up at 89 years. The association
      between BP and handgrip strength was analyzed by linear regression analysis.
      RESULTS: In middle-aged subjects, BP and handgrip strength were not statistically
      significantly associated. In oldest old subjects, higher systolic BP (SBP), mean
      arterial pressure (MAP), and pulse pressure (PP) were associated with higher
      handgrip strength after adjusting for comorbidity and medication use (all P <
      0.02). Furthermore, in oldest old subjects, changes in SBP, MAP, and PP after 4
      years was associated with declining handgrip strength (all, P < 0.05).
      CONCLUSION: In oldest old, higher BP is associated with better muscle strength.
      Further study is necessary to investigate whether BP is a potential modifiable
      risk factor for prevention of age-associated decline in muscle strength.

PMID- 20814410
TI  - The short-term effect of diacylglycerol oil consumption on total and dietary fat
      utilization in overweight women.
AB  - Diacylglycerol (DAG) is a natural component of edible oils with metabolic
      characteristics distinct from those of triacylglycerol (TAG). Consumption of DAG
      oil (containing > 80% DAG) induces greater fat oxidation than consumption of TAG
      oil. We compared the effects of 4 days of DAG oil consumption with those of TAG
      oil consumption on total and dietary fat oxidation over 24 h in overweight women
      using a whole-room respiratory chamber. Overweight (BMI (kg/m2) >= 25) females
      participated in this double-blind, crossover-controlled trial. The subjects
      consumed test diets containing either TAG or DAG oil as 15% of their total
      caloric intake (mean test oil intake was 33.0 +/- 3.1 g/day) during each 4-day
      treatment. Fat oxidation and energy expenditure were measured in a respiratory
      chamber on the 4th day of each treatment. Compared with TAG oil, DAG oil
      consumption significantly increased total fat oxidation and dietary fat oxidation
      in overweight subjects. Total energy expenditure (TEE) and carbohydrate (CHO)
      oxidation did not significantly differ between DAG oil and TAG oil consumption in
      overweight subjects. Compared with TAG oil, DAG oil consumption enhanced total
      fat oxidation and dietary fat oxidation in overweight subjects. The enhanced fat
      metabolism in overweight subjects that consumed DAG oil partly explains the
      greater loss of body weight and body fat related to DAG oil consumption in weight
      loss studies.

PMID- 20814412
TI  - Food supplements for body weight reduction: a systematic review of systematic
      reviews.

PMID- 20814411
TI  - Eicosapentaenoic acid and rosiglitazone increase adiponectin in an additive and
      PPARgamma-dependent manner in human adipocytes.
AB  - Adiponectin, an anti-inflammatory and insulin-sensitizing protein secreted from
      adipose tissue, may be modulated by dietary fatty acids, although the mechanism
      is not fully known. Our objective was to investigate the effect of long-chain n-3
      polyunsaturated fatty acids (PUFAs) on adiponectin in cultured human adipocytes,
      and to elucidate the role of peroxisome proliferator-activated receptor-gamma
      (PPARgamma) in this regulation. Isolated human adipocytes were cultured for 48 h
      with 100 umol/l eicosapentaenoic acid (C20:5n-3, EPA), docosahexaenoic acid
      (C22:6n-3, DHA), palmitic acid (C16:0), 100 umol/l EPA plus 100 umol/l DHA, or
      bovine serum albumin (control). Additionally, adipocytes were treated for 48 h
      with a PPARgamma antagonist (BADGE) or agonist (rosiglitazone) in isolation or in
      conjunction with either EPA or DHA. At 48 h, EPA and DHA increased (P < 0.05)
      adiponectin secretion by 88 and 47%, respectively, while EPA, but not DHA, also
      increased (136%, P < 0.001) cellular adiponectin protein. Interestingly,
      PPARgamma antagonism completely abolished the DHA-mediated increase in secreted
      adiponectin, but only partially attenuated the EPA-mediated response. Thus, EPA's
      effects on adiponectin do not appear to be entirely PPARgamma mediated.
      Rosiglitazone increased (P < 0.001) the secreted and cellular adiponectin protein
      (90 and 582%, respectively). Finally, the effects of EPA and rosiglitazone on
      adiponectin secretion were additive (+230% at 48 h combined, compared to 121 and
      124% by EPA or rosiglitazone alone, respectively). Overall, our findings
      emphasize the therapeutic importance of long-chain n-3 PUFA alone, or in
      combination with a PPARgamma agonist, as a stimulator of adiponectin, a key
      adipokine involved in obesity and related diseases.

PMID- 20814413
TI  - Transient increase in HDL-cholesterol during weight gain by hyperalimentation in
      healthy subjects.
AB  - Determination of lipid levels is fundamental in cardiovascular risk assessment.
      We studied the short-term effects of fast food-based hyperalimentation on lipid
      levels in healthy subjects. Twelve healthy men and six healthy women with a mean
      age of 26 +/- 6.6 years and an aged-matched control group were recruited for this
      prospective interventional study. Subjects in the intervention group aimed for a
      body weight increase of 5-15% by doubling the baseline caloric intake by eating
      at least two fast food-based meals a day in combination with adoption of a
      sedentary lifestyle for 4 weeks. This protocol induced a weight gain from 67.6 +/
      9.1 kg to 74.0 +/- 11 kg (P < 0.001). A numerical increase in the levels of high
      density lipoprotein (HDL)-cholesterol occurred in all subjects during the study
      and this was apparent already at the first week in 16/18 subjects (mean increase
      at week 1: +22.0 +/- 16%, range from -7 to +50%), whereas the highest level of
      HDL during the study as compared with baseline values varied from +6% to +58%
      (mean +31.6 +/- 15%). The intake of saturated fat in the early phase of the trial
      related positively with the HDL-cholesterol-increase in the second week (r =
      0.53, P = 0.028). Although the levels of insulin doubled at week 2, the increase
      in low-density lipoprotein (LDL)-cholesterol was only +12 +/- 17%, and there was
      no statistically significant changes in fasting serum triglycerides. We conclude
      that hyperalimentation can induce a fast but transient increase in HDL
      cholesterol that is of clinical interest when estimating cardiovascular risk
      based on serum lipid levels.

PMID- 20814414
TI  - Chefs' opinions about reducing the calorie content of menu items in restaurants.
AB  - Modifying the energy content of foods, particularly foods eaten away from home,
      is important in addressing the obesity epidemic. Chefs in the restaurant industry
      are uniquely placed to influence the provision of reduced-calorie foods, but
      little is known about their opinions on this issue. A survey was conducted among
      chefs attending US culinary meetings about strategies for creating reduced
      calorie foods and opportunities for introducing such items on restaurant menus.
      The 432 respondents were from a wide variety of employment positions and the
      majority had been in the restaurant industry for >= 20 years. Nearly all chefs
      (93%) thought that the calories in menu items could be reduced by 10-25% without
      customers noticing. To decrease the calories in two specific foods, respondents
      were more likely to select strategies for reducing energy density than for
      reducing portion size (P < 0.004). Low consumer demand was identified as the
      greatest barrier to including reduced-calorie items on the menu by 38% of chefs,
      followed by the need for staff skills and training (24%), and high ingredient
      cost (18%). The majority of respondents (71%) ranked taste as the most
      influential factor in the success of reduced-calorie items (P < 0.0001). The
      results of this survey indicate that opportunities exist for reducing the energy
      content of restaurant items. Ongoing collaboration is needed between chefs and
      public health professionals to ensure that appealing reduced-calorie menu items
      are more widely available in restaurants and that research is directed toward
      effective ways to develop and promote these items.

PMID- 20814415
TI  - Insulin sensitivity as a mediator of the relationship between BMI and working
      memory-related brain activation.
AB  - Midlife obesity is associated with cognitive deficits and cerebral atrophy in
      older age. However, little is known about the early signs of these deleterious
      brain effects or the physiological mechanisms that underlie them. Functional
      magnetic resonance imaging (fMRI) allows us to detect early changes in brain
      response to cognitive challenges while behavioral performance is still intact.
      Accordingly, we examined the impact of obesity on functional activation during a
      2-Back task in 32 cognitively normal middle-aged adults, who were classified into
      normal, overweight, and obese groups according to BMI. Additionally, we examined
      insulin sensitivity as a potential mediator of the relationship between BMI and
      brain activation. Insulin sensitivity is of special interest because insulin is
      strongly associated with both obesity and central nervous system functioning.
      Group differences in task-related brain activation were examined in a priori
      regions of interest (ROIs) using ANOVA. The obese BMI group displayed
      significantly lower task-related activation in the right parietal cortex, BA
      40/7, (F(2,29) = 5.26, P = 0.011) than the normal (P = 0.016) and overweight (P =
      0.047) BMI groups. Linear regression and bootstrapping methods for assessing
      indirect effects indicated that insulin sensitivity fully mediated the
      relationship between task-related activation in the right parietal cortex and BMI
      ((F(3,28) = 9.03, P = 0.000), beta = 0.611, P = 0.001, 95% confidence interval: 
      2.548 to -0.468). In conclusion, obesity in middle age was related to alterations
      in brain activation during a cognitive challenge and this association appeared to
      be mediated by insulin sensitivity.

PMID- 20814416
TI  - Higher adiponectin levels predict greater weight gain in healthy women in the
      Nurses' Health Study.
AB  - Adiponectin and resistin's possible roles in weight regulation have received
      little attention. We tested the hypothesis that adipokine levels predict future
      weight gain in women in the Nurses' Health Study. Among women who provided blood
      samples in 1990, we studied 1,063 women who did not develop diabetes ("healthy")
      and 984 women who subsequently developed diabetes. Total and high-molecular
      weight (HMW) adiponectin and resistin levels were measured using enzyme-linked
      immunosorbent assay. Women who did not developed diabetes had a mean BMI of 26.3
      +/- 6.0 kg/m(2) at baseline and gained 2.0 +/- 6.1 kg over 4 years. Women who
      developed diabetes had a mean BMI of 30.1 +/- 5.4 kg/m(2) at baseline, and gained
      2.4 +/- 7.1 kg over 4 years. In women who did not developed diabetes, higher
      baseline levels of total and HMW adiponectin were associated with significantly
      greater weight gain after adjustment for age, BMI, physical activity, diet, and
      other covariates: women in the highest quintile of total adiponectin gained 3.18
      kg compared to women in the lowest quintile who gained 0.80 kg (fully adjusted; P
      for trend <0.0001). Adiponectin was not significantly associated with weight gain
      in women who subsequently developed diabetes. Resistin levels were not associated
      with weight gain in either women who did or did not develop diabetes during the
      follow-up. We conclude that elevated adiponectin levels are associated with
      higher weight gain in healthy women, independent of confounding risk factors.
      High adiponectin production by adipocytes might be a sign of "healthy" adipose
      tissue with further capacity to store fat.

PMID- 20814417
TI  - Resting heart rate as a predictor of body weight gain in the early stage of
      hypertension.
AB  - We did a prospective study to investigate whether clinic heart rate (HR) and 24-h
      ambulatory HR were independent predictors of subsequent increase in body weight
      (BW) in young subjects screened for stage 1 hypertension. The study was conducted
      in 1,008 subjects from the Hypertension and Ambulatory Recording Venetia Study
      (HARVEST) followed for an average of 7 years. Ambulatory HR was obtained in 701
      subjects. Data were adjusted for lifestyle factors and several confounders.
      During the follow-up BW increased by 2.1 +/- 7.2 kg in the whole cohort. Both
      baseline clinic HR (P = 0.007) and 24-h HR (P = 0.013) were independent
      predictors of BMI at study end. In addition, changes in HR during the follow-up
      either measured in the clinic (P = 0.036) or with 24-h recording (P = 0.009) were
      independent associates of final BMI. In a multivariable Cox regression, baseline
      BMI (P < 0.001), male gender (P < 0.001), systolic blood pressure (BP) (P =
      0.01), baseline clinic HR (P = 0.02), and follow-up changes in clinic HR (P <
      0.001) were independent predictors of overweight (Ov) or obesity (Ob) at the end
      of the follow-up. Follow-up changes in ambulatory HR (P = 0.01) were also
      independent predictors of Ov or Ob. However, when both clinic and ambulatory HRs
      were included in the same Cox model, only baseline clinic HR and its change
      during the follow-up were independent predictors of outcome. In conclusion,
      baseline clinic HR and HR changes during the follow-up are independent predictors
      of BW gain in young persons screened for stage 1 hypertension suggesting that
      sympathetic nervous system activity may play a role in the development of Ob in
      hypertension.

PMID- 20814418
TI  - Functional effects of adiponectin on endothelial progenitor cells.
AB  - Adiponectin is an adipokine whose plasma levels are inversely correlated to
      metabolic syndrome components. Adiponectin protects against atherosclerosis and
      decreases risks in myocardial infarction. Endothelial progenitor cells (EPCs) are
      a heterogeneous population of circulating cells involved in vascular repair and
      neovascularization. EPCs number is reduced in patients with cardiovascular
      disease. We hypothesize that the positive effects of adiponectin against
      atherosclerosis are explained in part by its interactions with EPCs. Cells were
      obtained from healthy volunteers' blood by mononuclear cell isolation and plating
      on collagen-coated dishes. Three sub-populations of EPCs were identified and
      characterized using flow cytometry. EPCs' expression of adiponectin receptors,
      AdipoR1, and AdipoR2 was evaluated by quantitative PCR. The effects of
      recombinant adiponectin on EPCs' susceptibility to apoptosis were assessed.
      Finally, expression of neutrophil elastase by EPCs and activity of this enzyme on
      adiponectin processing were assessed. Quantitative PCR analysis of EPCs mRNAs
      showed that AdipoR1 mRNA is expressed at higher levels than AdipoR2. Expression
      of AdipoR1 protein was confirmed by western blot. Adiponectin significantly
      increased survival of two sub-populations of EPCs in conditions of serum
      deprivation. Such effect could not be demonstrated in the third EPCs sub
      population. We also demonstrated that EPCs, particularly one sub-population,
      express neutrophil elastase. Neutrophil elastase activity was confirmed in EPCs'
      conditioned media. Adiponectin protects some EPCs sub-populations against
      apoptosis and therefore could modulate EPCs ability to induce repair of vascular
      damage. Neutrophil elastase activity of EPCs could locally modulate adiponectin
      activity by its involvement in the generation of the globular form of
      adiponectin.

PMID- 20814419
TI  - Human-IAPP disrupts the autophagy/lysosomal pathway in pancreatic beta-cells:
      protective role of p62-positive cytoplasmic inclusions.
AB  - In type II diabetes (T2DM), there is a deficit in beta-cells, increased beta-cell
      apoptosis and formation of intracellular membrane-permeant oligomers of islet
      amyloid polypeptide (IAPP). Human-IAPP (h-IAPP) is an amyloidogenic protein co
      expressed with insulin by beta-cells. IAPP expression is increased with obesity,
      the major risk factor for T2DM. In this study we report that increased expression
      of human-IAPP led to impaired autophagy, due at least in part to the disruption
      of lysosome-dependent degradation. This action of IAPP to alter lysosomal
      clearance in vivo depends on its propensity to form toxic oligomers and is
      independent of the confounding effect of hyperglycemia. We report that the
      scaffold protein p62 that delivers polyubiquitinated proteins to autophagy may
      have a protective role against human-IAPP-induced apoptosis, apparently by
      sequestrating protein targets for degradation. Finally, we found that inhibition
      of lysosomal degradation increases vulnerability of beta-cells to h-IAPP-induced
      toxicity and, conversely, stimulation of autophagy protects beta-cells from h
      IAPP-induced apoptosis. Collectively, these data imply an important role for the
      p62/autophagy/lysosomal degradation system in protection against toxic oligomer
      induced apoptosis.

PMID- 20814420
TI  - Cancer: an old disease, a new disease or something in between?
AB  - In industrialized societies, cancer is second only to cardiovascular disease as a
      cause of death. The history of this disorder has the potential to improve our
      understanding of disease prevention, aetiology, pathogenesis and treatment. A
      striking rarity of malignancies in ancient physical remains might indicate that
      cancer was rare in antiquity, and so poses questions about the role of
      carcinogenic environmental factors in modern societies. Although the rarity of
      cancer in antiquity remains undisputed, the first published histological
      diagnosis of cancer in an Egyptian mummy demonstrates that new evidence is still
      forthcoming.

PMID- 20814422
TI  - A genetic system to assess in vivo the functions of histones and histone
      modifications in higher eukaryotes.
AB  - Despite the fundamental role of canonical histones in nucleosome structure, there
      is no experimental system for higher eukaryotes in which basic questions about
      histone function can be directly addressed. We developed a new genetic tool for
      Drosophila melanogaster in which the canonical histone complement can be replaced
      with multiple copies of experimentally modified histone transgenes. This new
      histone-replacement system provides a well-defined and direct cellular assay
      system for histone function with which to critically test models in chromatin
      biology dealing with chromatin assembly, variant histone functions and the
      biological significance of distinct histone modifications in a multicellular
      organism.

PMID- 20814423
TI  - Helicobacter pylori HtrA is a new secreted virulence factor that cleaves E
      cadherin to disrupt intercellular adhesion.
AB  - Mammalian and prokaryotic high-temperature requirement A (HtrA) proteins are
      chaperones and serine proteases with important roles in protein quality control.
      Here, we describe an entirely new function of HtrA and identify it as a new
      secreted virulence factor from Helicobacter pylori, which cleaves the ectodomain
      of the cell-adhesion protein E-cadherin. E-cadherin shedding disrupts epithelial
      barrier functions allowing H. pylori designed to access the intercellular space.
      We then designed a small-molecule inhibitor that efficiently blocks HtrA
      activity, E-cadherin cleavage and intercellular entry of H. pylori.

PMID- 20814421
TI  - KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal
      adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is characterized by near-universal
      mutations in KRAS and frequent deregulation of crucial embryonic signalling
      pathways, including the Hedgehog (Hh) and Wnt-beta-catenin cascades. The creation
      of mouse models that closely resemble the human disease has provided a platform
      to better understand when and in which cell types these pathways are misregulated
      during PDAC development. Here we examine the central part that KRAS plays in the
      biology of PDAC, and how the timing and location of Hh and Wnt-beta-catenin
      signalling dictate the specification and oncogenic properties of PDAC.

PMID- 20814424
TI  - Role of the RNA/DNA kinase Grc3 in transcription termination by RNA polymerase I.
AB  - Transcription termination by RNA polymerase I in Saccharomyces cerevisiae is
      mediated by a 'torpedo' mechanism: co-transcriptional RNA cleavage by Rnt1 at the
      ribosomal DNA 3'-region generates a 5'-end that is recognized by the 5'-3'
      exonuclease Rat1; this degrades the downstream transcript and eventually causes
      termination. In this study, we identify Grc3 as a new factor involved in this
      process. We demonstrate that GRC3, an essential gene of previously unknown
      function, encodes a polynucleotide kinase that is required for efficient
      termination by RNA polymerase I. We propose that it controls the phosphorylation
      status of the downstream Rnt1 cleavage product and thereby regulates its
      accessibility to the torpedo Rat1.

PMID- 20814425
TI  - Green with underappreciation.
AB  - "What do cells, genes, transposons, telomeres, RNA silencing and DNA
      recombination have in common? They were all discovered in plants." This is how
      Rob Martienssen emphasizes the contributions of plant research. We asked plant
      scientists whether their field is getting adequate support and proper recognition
      and heard a resounding "no."

PMID- 20814428
TI  - A general model for multilocus epistatic interactions in case-control studies.
AB  - BACKGROUND: Epistasis, i.e., the interaction of alleles at different loci, is
      thought to play a central role in the formation and progression of complex
      diseases. The complexity of disease expression should arise from a complex
      network of epistatic interactions involving multiple genes. METHODOLOGY: We
      develop a general model for testing high-order epistatic interactions for a
      complex disease in a case-control study. We incorporate the quantitative genetic
      theory of high-order epistasis into the setting of cases and controls sampled
      from a natural population. The new model allows the identification and testing of
      epistasis and its various genetic components. CONCLUSIONS: Simulation studies
      were used to examine the power and false positive rates of the model under
      different sampling strategies. The model was used to detect epistasis in a case
      control study of inflammatory bowel disease, in which five SNPs at a candidate
      gene were typed, leading to the identification of a significant three-locus
      epistasis.

PMID- 20814427
TI  - Polymorphic nucleic Acid binding of bioactive isoquinoline alkaloids and their
      role in cancer.
AB  - Bioactive alkaloids occupy an important position in applied chemistry and play an
      indispensable role in medicinal chemistry. Amongst them, isoquinoline alkaloids
      like berberine, palmatine and coralyne of protoberberine group, sanguinarine of
      the benzophenanthridine group, and their derivatives represent an important class
      of molecules for their broad range of clinical and pharmacological utility. In
      view of their extensive occurrence in various plant species and significantly low
      toxicities, prospective development and use of these alkaloids as effective
      anticancer agents are matters of great current interest. This review has focused
      on the interaction of these alkaloids with polymorphic nucleic acid structures (B
      form, A-form, Z-form, H(L)-form, triple helical form, quadruplex form) and their
      topoisomerase inhibitory activity reported by several research groups using
      various biophysical techniques like spectrophotometry, spectrofluorimetry,
      thermal melting, circular dichroism, NMR spectroscopy, electrospray ionization
      mass spectroscopy, viscosity, isothermal titration calorimetry, differential
      scanning calorimetry, molecular modeling studies, and so forth, to elucidate
      their mode and mechanism of action for structure-activity relationships. The DNA
      binding of the planar sanguinarine and coralyne are found to be stronger and
      thermodynamically more favoured compared to the buckled structure of berberine
      and palmatine and correlate well with the intercalative mechanism of sanguinarine
      and coralyne and the partial intercalation by berberine and palmatine. Nucleic
      acid binding properties are also interpreted in relation to their anticancer
      activity.

PMID- 20814429
TI  - Innate immune function in placenta and cord blood of hepatitis C--seropositive
      mother-infant dyads.
AB  - Vertical transmission accounts for the majority of pediatric cases of hepatitis C
      viral (HCV) infection. In contrast to the adult population who develop persistent
      viremia in approximately 80% of cases following exposure, the rate of mother-to
      child transmission (2-6%) is strikingly low. Protection from vertical
      transmission likely requires the coordination of multiple components of the
      immune system. Placenta and decidua provide a direct connection between mother
      and infant. We hypothesized that innate immune responses would differ across the
      three compartments (decidua, placenta and cord blood) and that hepatitis C
      exposure would modify innate immunity in these tissues. The study was comprised
      of HCV-infected and healthy control mother and infant pairs from whom cord blood,
      placenta and decidua were collected with isolation of mononuclear cells.
      Multiparameter flow cytometry was performed to assess the phenotype,
      intracellular cytokine production and cytotoxicity of the cells. In keeping with
      a model where the maternal-fetal interface provides antiviral protection, we
      found a gradient in proportional frequencies of NKT and gammadelta-T cells being
      higher in placenta than cord blood. Cytotoxicity of NK and NKT cells was enhanced
      in placenta and placental NKT cytotoxicity was further increased by HCV
      infection. HCV exposure had multiple effects on innate cells including a decrease
      in activation markers (CD69, TRAIL and NKp44) on NK cells and a decrease in
      plasmacytoid dendritic cells in both placenta and cord blood of exposed infants.
      In summary, the placenta represents an active innate immunological organ that
      provides antiviral protection against HCV transmission in the majority of cases;
      the increased incidence in preterm labor previously described in HCV-seropositive
      mothers may be related to enhanced cytotoxicity of NKT cells.

PMID- 20814432
TI  - PPARgamma Ligand as a Promising Candidate for Colorectal Cancer Chemoprevention:
      A Pilot Study.
AB  - Activating synthetic ligands for peroxisome proliferator-activated receptor gamma
      (PPARgamma), such as pioglitazone, are commonly used to treat persons with
      diabetes mellitus with improvement of insulin resistance. Several reports have
      clearly demonstrated that PPARgamma ligands could inhibit colorectal cancer cell
      growth and induce apoptosis. Meanwhile, aberrant crypt foci (ACF) have come to be
      established as a biomarker of the risk of CRC in azoxymethane-treated mice and
      rats. In humans, ACF can be detected using magnifying colonoscopy. Previously,
      CRC and adenoma were used as a target for chemopreventive agents, but it needs a
      long time to evaluate, however, ACF can be a surrogate marker of CRC even for a
      brief period. In this clinical study, we investigated the chemopreventive effect
      of pioglitazone on the development of human ACF as a surrogate marker of CRC.
      Twenty-nine patients were divided into two groups, 20 were in the endoscopically
      normal control group and 9 were in the pioglitazone (15 mg/day) group, and ACF
      and adenoma were examined before and after 1-month treatment. The number of ACF
      was significantly decreased (5.8 +/- 1.1 to 3.3 +/- 2.3) after 1 month of
      pioglitazone treatment, however, there was no significant change in the number of
      crypts/ACF or in the number and size of adenomas. Pioglitazone may have a
      clinical application as a cancer-preventive drug. This investigation is just a
      pilot study, therefore, further clinical studies are needed to show that the
      PPARgamma ligand may be a promising candidate as a chemopreventive agent for
      colorectal carcinogenesis.

PMID- 20814433
TI  - PPARs: Nuclear Receptors Controlled by, and Controlling, Nutrient Handling
      through Nuclear and Cytosolic Signaling.
AB  - Peroxisome proliferator-activated receptors (PPARs), which are known to regulate
      lipid homeostasis, are tightly controlled by nutrient availability, and they
      control nutrient handling. In this paper, we focus on how nutrients control the
      expression and action of PPARs and how cellular signaling events regulate the
      action of PPARs in metabolically active tissues (e.g., liver, skeletal muscle,
      heart, and white adipose tissue). We address the structure and function of the
      PPARs, and their interaction with other nuclear receptors, including PPAR cross
      talk. We further discuss the roles played by different kinase pathways, including
      the extracellular signal-regulated kinases/mitogen-activated protein kinase (ERK
      MAPK), AMP-activated protein kinase (AMPK), Akt/protein kinase B (Akt/PKB), and
      the NAD+-regulated protein deacetylase SIRT1, serving to control the activity of
      the PPARs themselves as well as that of a key nutrient-related PPAR coactivator,
      PPARgamma coactivator-1alpha (PGC-1alpha). We also highlight how currently
      applied nutrigenomic strategies will increase our understanding on how nutrients
      regulate metabolic homeostasis through PPAR signaling.

PMID- 20814434
TI  - The number of grafted fragments affects the outcome of testis tissue xenografting
      from piglets into recipient mice.
AB  - To optimize the procedure for testis tissue xenografting, we grafted 2, 4, 8, or
      16 small fragments of immature porcine testis tissue under the back skin of
      immunodeficient castrated mice (n = 10 mice/group). At 8 months post grafting,
      the graft recovery rate did not differ between groups; however, not only the
      total but also the average graft weights were higher (by approximately 12-fold
      and approximately 2.5-fold, resp.) in mice receiving 16 fragments than those
      receiving 2 fragments (P < .05). The recipient mice with 16 fragments had the
      largest vesicular glands (indicators of testosterone release by the grafts)
      compared with those with 2 fragments (P = .007). The grafts in the group of 16
      fragments also had more (P < .05) percentage of tubules with round spermatids
      than those of the group of mice receiving 2 fragments. Therefore, recipient mice
      can be grafted with at least 16 testis tissue fragments for optimal results.

PMID- 20814435
TI  - Practical applications of sperm selection techniques as a tool for improving
      reproductive efficiency.
AB  - Modern biotechnologies are used extensively in the animal breeding industry
      today. Therefore, it is essential that sperm handling procedures do not modulate
      the normal physiological mechanisms occurring in the female reproductive tract.
      In this paper, the different selection mechanisms occurring in vivo are described
      briefly, together with their relevance to artificial insemination, followed by a
      detailed description of the different selection processes used in reproductive
      biotechnologies. These selection methods included fractionated semen collection,
      cryopreservation, biomimetic sperm selection, selection based on hyaluronic acid
      binding, and last, but not least, sperm sex selection. Biomimetic sperm selection
      for AI or for cryopreservation could improve pregnancy rates and help to reverse
      the decline in fertility seen in several domestic species over the recent
      decades. Similarly, selection for hyaluronic acid binding sites may enable the
      most mature spermatozoa to be selected for IVF or ICSI.

PMID- 20814436
TI  - Encoding Dissimilarity Data for Statistical Model Building.
AB  - We summarize, review and comment upon three papers which discuss the use of
      discrete, noisy, incomplete, scattered pairwise dissimilarity data in statistical
      model building. Convex cone optimization codes are used to embed the objects into
      a Euclidean space which respects the dissimilarity information while controlling
      the dimension of the space. A "newbie" algorithm is provided for embedding new
      objects into this space. This allows the dissimilarity information to be
      incorporated into a Smoothing Spline ANOVA penalized likelihood model, a Support
      Vector Machine, or any model that will admit Reproducing Kernel Hilbert Space
      components, for nonparametric regression, supervised learning, or semi-supervised
      learning. Future work and open questions are discussed. The papers are: F. Lu, S.
      Keles, S. Wright and G. Wahba 2005. A framework for kernel regularization with
      application to protein clustering. Proceedings of the National Academy of
      Sciences 102, 12332-1233.G. Corrada Bravo, G. Wahba, K. Lee, B. Klein, R. Klein
      and S. Iyengar 2009. Examining the relative influence of familial, genetic and
      environmental covariate information in flexible risk models. Proceedings of the
      National Academy of Sciences 106, 8128-8133F. Lu, Y. Lin and G. Wahba. Robust
      manifold unfolding with kernel regularization. TR 1008, Department of Statistics,
      University of Wisconsin-Madison.

PMID- 20814437
TI  - Opposing effects of omega-3 and omega-6 long chain polyunsaturated Fatty acids on
      the expression of lipogenic genes in omental and retroperitoneal adipose depots
      in the rat.
AB  - This study aimed to determine the effect of varying dietary intake of the major n
      3 PUFA in human diets, alpha-linolenic acid (ALA; 18 : 3n-3), on expression of
      lipogenic genes in adipose tissue. Rats were fed diets containing from 0.095%en
      to 6.3%en ALA and a constant n-6 PUFA level for 3 weeks. Samples from distinct
      adipose depots (omental and retroperitoneal) were collected and mRNA expression
      of the pro-lipogenic transcription factors Sterol-Retinoid-Element-Binding
      Protein1c (SREBP1c) and Peroxisome Proliferator Activated Receptor-gamma
      (PPARgamma), lipogenic enzymes Sterol-coenzyme Desaturase1 (SCD-1), Fatty Acid
      Synthase (FAS), lipoprotein lipase (LPL) and glycerol-3-phosphate dehydrogenase
      (G3PDH) and adipokines leptin and adiponectin determined by qRT-PCR. Increasing
      dietary ALA content resulted in altered expression of SREBP1c, FAS and G3PDH mRNA
      in both adipose depots. SREBP1c mRNA expression was related directly to n-6 PUFA
      concentrations (omental, r(2) = .71; P < .001; Retroperitoneal, r(2) = .20; P <
      .002), and inversely to n-3 PUFA concentrations (omental, r(2) = .59; P < .001;
      Retroperitoneal, r(2) = .19; P < .005) independent of diet. The relationship
      between total n-6 PUFA and SREBP1c mRNA expression persisted when the effects of
      n-3 PUFA were controlled for. Altering red blood cell concentrations of n-3 PUFA
      is thus associated with altered expression of lipogenic genes in a depot-specific
      manner and this effect is modulated by prevailing n-6 PUFA concentrations.

PMID- 20814438
TI  - Efficacy of tuohy needle in oocytes collection from excised mare ovaries.
AB  - TWO METHODS HAVE BEEN DESCRIBED TO RECOVER OOCYTES FROM EQUINE FOLLICLES IN
      EXCISED OVARIES: aspiration and scraping. Aim of this work was to develop an
      effective method for collecting equine oocytes using Tuohy needle and comparing
      this technique to aspiration and scraping, with or without tunica albuginea
      removal. This hollow hypodermic needle, usually employed for inserting epidural
      catheters, is designed with a slightly curved tip, shaped similar to a small
      curette. In unpeeled ovaries, the recovery rates of Tuohy needle group was higher
      (P < .05) than in the 16 g needle aspiration and in the scraped ovaries (57%
      versus 36% and 47%) while the rate of cumulus-intact oocytes was higher than
      aspiration (46.9% versus 39.36%) but lower than scraping (46.97%) (P < .001). In
      unpeeled ovaries there was significant difference in maturation rate of oocytes
      recovered by Tuohy needle in respect to peeled ovaries (58.54% versus 50.17%,
      resp.). Combination of aspiration and scraping by Tuohy needle allows a faster
      and reliable collection of oocytes suitable for horse IVM.

PMID- 20814440
TI  - Epigenetic regulatory mechanisms associated with infertility.
AB  - Infertility is a complex human condition and is known to be caused by numerous
      factors including genetic alterations and abnormalities. Increasing evidence from
      studies has associated perturbed epigenetic mechanisms with spermatogenesis and
      infertility. However, there has been no consensus on whether one or a collective
      of these altered states is responsible for the onset of infertility. Epigenetic
      alterations involve changes in factors that regulate gene expression without
      altering the physical sequence of DNA. Understanding these altered epigenetic
      states at the genomic level along with higher order organisation of chromatin in
      genes associated with infertility and pericentromeric regions of chromosomes,
      particularly 9 and Y, could further identify causes of idiopathic infertility.
      Determining the association between DNA methylation, chromatin state, and
      noncoding RNAs with the phenotype could further determine what possible
      mechanisms are involved. This paper reviews certain mechanisms of epigenetic
      regulation with particular emphasis on their possible role in infertility.

PMID- 20814442
TI  - Thymic epithelial tumor with heart metastasis in a horse.
AB  - Thymic malignancy is rare in horses. Thymic epithelial tumor was diagnosed in an
      18-year-old mare with invasion and metastasis to the pericardium and heart. At
      necropsy, the cranial thoracic cavity was obliterated by a large mass located in
      the thymic region and the right atrium was also expanded and effaced by a similar
      mass. Histologically, the neoplasm was composed of sheets of spindle cells with
      intraparenchymal Hassall's corpuscles and formation of pseudorosettes around
      blood vessels compatible with type A thymic epithelial tumor according to World
      Health Organization classification. The neoplastic cells were diffusely
      immunoreactive for cytokeratin and negative for vimentin, S100, neuron specific
      enolase, glial fibrillar acidic protein, chromogranin A, synaptophysin, CD3 and
      CD79a markers. To the authors' knowledge, cardiac invasion and distinct
      histological pattern of pseudorosette formation have not been described in equine
      thymic epithelial tumors previously.

PMID- 20814441
TI  - AMPK-Dependent Metabolic Regulation by PPAR Agonists.
AB  - Comprehensive studies support the notion that the peroxisome proliferator
      activated receptors, (PPARs), PPARalpha, PPARbeta/delta, and PPARgamma, regulate
      cell growth, morphogenesis, differentiation, and homeostasis. Agonists of each
      PPAR subtype exert their effects similarly or distinctly in different tissues
      such as liver, muscle, fat, and vessels. It is noteworthy that PPARalpha or
      PPARgamma agonists have pharmacological effects by modulating the activity of
      AMPK, which is a key cellular energy sensor. However, the role of AMPK in the
      metabolic effects of PPAR agonists has not been thoroughly focused. Moreover,
      AMPK activation by PPAR agonists seems to be independent of the receptor
      activation. This intriguing action of PPAR agonists may account in part for the
      mechanistic basis of the therapeutics in the treatment of metabolic disease. In
      this paper, the effects of PPAR agonists on metabolic functions were summarized
      with particular reference to their AMPK activity regulation.

PMID- 20814439
TI  - Coactivators in PPAR-Regulated Gene Expression.
AB  - Peroxisome proliferator-activated receptor (PPAR)alpha, beta (also known as
      delta), and gamma function as sensors for fatty acids and fatty acid derivatives
      and control important metabolic pathways involved in the maintenance of energy
      balance. PPARs also regulate other diverse biological processes such as
      development, differentiation, inflammation, and neoplasia. In the nucleus, PPARs
      exist as heterodimers with retinoid X receptor-alpha bound to DNA with
      corepressor molecules. Upon ligand activation, PPARs undergo conformational
      changes that facilitate the dissociation of corepressor molecules and invoke a
      spatiotemporally orchestrated recruitment of transcription cofactors including
      coactivators and coactivator-associated proteins. While a given nuclear receptor
      regulates the expression of a prescribed set of target genes, coactivators are
      likely to influence the functioning of many regulators and thus affect the
      transcription of many genes. Evidence suggests that some of the coactivators such
      as PPAR-binding protein (PBP/PPARBP), thyroid hormone receptor-associated protein
      220 (TRAP220), and mediator complex subunit 1 (MED1) may exert a broader
      influence on the functions of several nuclear receptors and their target genes.
      Investigations into the role of coactivators in the function of PPARs should
      strengthen our understanding of the complexities of metabolic diseases associated
      with energy metabolism.

PMID- 20814443
TI  - Hypermethylation of SOX2 Promoter in Endometrial Carcinogenesis.
AB  - This paper aimed at investigating the expression and methylation profiles of
      SOX2, a gene coding for the stem cell-related transcription factor SOX2, in
      endometrial carcinomas. By methylation-specific polymerase chain reaction (MS
      PCR), the methylation status of SOX2 promoter region in 72 endometrial carcinomas
      and 12 normal endometrial samples was examined. Methylated allele was found in
      37.5% (27/72) of endometrial carcinomas but only in 8.3% (1/12) of normal
      endometrial, significantly more frequent in cancers (P = .0472). SOX2 mRNA level
      was significantly reduced in endometrial carcinoma compared with nonneoplastic
      endometrium (P = .045). A significant correlation between SOX2 mRNA expression
      and hypermethylation of SOX2 was found (P = .024). Hypermethylation of SOX2
      tended to be more frequently found in type II serous or clear cell
      adenocarcinoma. SOX2 methylation was also significantly correlated with shorter
      survival of patients (P = .046). In conclusion, epigenetic mechanisms may play a
      crucial role on the transcriptional regulation of SOX2 and loss of SOX2
      expression may be related to endometrial carcinogenesis.

PMID- 20814444
TI  - Effects of oral, vaginal, and transdermal hormonal contraception on serum levels
      of coenzyme q(10), vitamin e, and total antioxidant activity.
AB  - The use of the transdermal contraceptive patch is associated with greater
      bioavailability of ethinyl estradiol (EE) compared with contraceptive vaginal
      ring or oral contraceptives (OC). We compared the influences of three
      contraceptive methods (OC, vaginal ring, and transdermal patch) on serum levels
      of coenzyme Q(10), alpha-tocopherol, gamma-tocopherol and total antioxidant
      capacity in premenopausal women. Blood samples from 30 premenopausal women who
      used hormonal contraception for at least 4 months were collected. Forty subjects
      who did not use any contraception were studied as control. Serum levels of
      coenzyme Q(10), alpha-tocopherol and gamma-tocopherol were measured by high
      pressure liquid chromatography. Serum samples were also assayed for total
      antioxidant capacity (TAOC). Serum levels of coenzyme Q(10) and alpha-tocopherol
      were found to be significantly lower (P < .05) in all three contraceptive users
      compared with controls. Contraceptive patch users had the lowest levels of
      coenzyme Q(10) levels compared with normal subjects. Serum TAOC levels were
      significantly lower (P < .05) among the contraceptive user groups. Alterations in
      coenzyme Q(10) and alpha-tocopherol induced by hormonal contraception and the
      potential effect(s) of exogenous ovarian hormones should be taken into
      consideration in future antioxidant research.

PMID- 20814445
TI  - Local Water Dynamics in Coacervated Polyelectrolytes Monitored Through Dynamic
      Nuclear Polarization-Enhanced H NMR.
AB  - We present the first study of quantifying the diffusion coefficient of
      interfacial water on polyelectrolyte surfaces of systems fully dispersed in bulk
      water under ambient conditions. Such measurements were made possible through the
      implementation of a recently introduced Dynamic Nuclear Polarization (DNP)
      technique to selectively amplify the nuclear magnetic resonance (NMR) signal of
      hydration water that is interacting with specifically located spin labels on
      polyelectrolyte surfaces. The merit of this novel capability is demonstrated in
      this report through the measurement of solvent microvisosity on the surface of
      two types of oppositely charged polyelectrolytes, when freely dissolved versus
      when complexed to form a liquid-liquid colloidal phase called complex
      coacervates. These complex coacervates were formed through electrostatic
      complexation between the imidazole-based cationic homopolymer poly(N
      vinylimidazole) (PVIm), and anionic polypeptide polyaspartate (PAsp) in the pH
      range of 4.5 - 6.0, under which conditions the coacervate droplets are highly
      fluidic yet densely packed with polyelectrolytes. We also investigated the
      rotational diffusion coefficients of the spin labels covalently bound to the
      polyelectrolyte chains for both PVIm and PAsp, showing a 5 fold change in the
      rotational correlation time as well as anisotropy parameter upon coacervation,
      which represents a surprisingly small decrease given the high polymer
      concentration inside the dense microdroplets. For both DNP and ESR experiments,
      the polymers were covalently tagged with stable nitroxide radical spin labels (~1
      wt %) to probe the local solvent and polymer segment dynamics. We found that the
      surface water diffusion coefficients near uncomplexed PVIm and PAsp at pH 8
      differ, and are around D~1.3*10(-9)m(2) / s. In contrast, inside the complex
      coacervate phase, the water diffusion coefficient in the immediate vicinity of
      either polyelectrolyte was D~ 0.25*10(-9)m(2) / s, which is about an order of
      magnitude smaller than the bulk water self diffusion coefficient, and yet orders
      of magnitude greater than that of associated, bound, hydration water. This
      observation suggests the existence of measurable water inside complex coacervates
      with relatively high diffusion and exchange dynamics, implying that water moves
      in nanometer-scale pore spaces as opposed to being structurally bound or even
      absent. We infer from our observation that the PVIm and PAsp chains are
      undergoing roughly pairwise association, so that largely charge neutralized
      species compose the concentrated, yet fluidic and partially hydrated coacervate
      cores.

PMID- 20814446
TI  - Impact of Moderate Calorie Restriction on the Reproductive Neuroendocrine Axis of
      Male Rhesus Macaques.
AB  - The impact of moderate calorie restriction on reproductive neuroendocrine
      function was investigated in young adult male rhesus macaques (Macaca mulatta).
      The animals were subjected to either 30% calorie restriction (CR; n=5), or were
      fed a standard control diet (CON; n=5), starting during their peripubertal
      period. Plasma LH and testosterone concentrations were examined after 7 years of
      differential dietary treatment, and were found to be similar in both groups, both
      during the day and during the night. Microarray profiling of pituitary gland and
      testicular gene expression was performed after 8 years of treatment, using
      GeneChip(r) Rhesus Macaque Genome Arrays (Affymetrix), and showed very little
      effect of caloric restriction. Using a 1.5-fold difference threshold, our
      microarray analysis revealed differential expression of only 145 probesets in the
      pituitary gland and 260 in the testes, out of a total of >54,000. Semi
      quantitative RT-PCR performed on pituitary gland mRNA corroborated the microarray
      findings for selected modulated genes, including TSH receptor (TSHR) and sperm
      specific antigen 2 (SSFA2). Most notably, significantly lower expression of TSH
      receptor mRNA was observed in the pituitary of CR compared to CON animals. Also,
      significantly lower expression of the glycoprotein hormone alpha subunit (CGA)
      was observed in CR animals, and this finding was further corroborated using
      quantitative real-time RT-PCR. No significant diet-induced changes were detected
      in the testis for genes associated with reproduction, circadian clocks, or
      oxidative stress. There is mounting evidence that CR may promote health and
      longevity in a wide range of organisms, including nonhuman primates. Importantly,
      our data suggest that moderate CR has no obvious lasting detrimental effect on
      the reproductive neuroendocrine axis of long-lived primates, and has only a
      modest influence on pituitary and testicular gene expression.

PMID- 20814447
TI  - How HIV treatment could result in effective prevention.
AB  - As the number of HIV infections continues to surpass treatment capacity, new HIV
      prevention strategies are imperative. Beyond individual clinical benefits, by
      rendering an individual less infectious, expanding access to highly active
      antiretroviral therapy (HAART) could also have a larger public health impact of
      curbing new HIV infections. Recent guidelines have moved towards initiating HAART
      at higher CD4 cell counts, thus increasing the number of individuals in need of
      treatment. A new treatment strategy is wanting that can simultaneously curb the
      epidemic and provide necessary treatment to those most in need. A recent debate
      has centered on whether an expansion of free and universal treatment, regardless
      of CD4 cell count, could be a means of HIV prevention. In light of the growing
      access to HAART in resource-limited settings and increasing evidence suggesting
      the clinical and prevention benefits of initiating treatment at higher CD4 cell
      counts, it is conceivable that, in the future, HAART will be an integral part of
      both individual-level clinical treatment programs as well as public health-based
      HIV prevention interventions.

PMID- 20814448
TI  - Noroviruses - State of the Art.
AB  - Noroviruses are a common cause of both endemic and epidemic gastroenteritis.
      These highly infectious viruses usually cause self-limited disease, but chronic
      infections occur in highly immunocompromised patients and unusual manifestations
      are also being described in some populations. Histoblood-group antigen expression
      is now recognized as an important susceptibility factor for many norovirus
      strains, but a correlate of acquired immunity to infection or illness has not yet
      been identified. Currently, treatment and prevention strategies rely on non
      specific measures. However, virus-like particles containing capsid antigens are
      undergoing evaluation as a vaccine candidate for illness prevention. This article
      reviews the biologic properties, epidemiology, clinical features, host
      susceptibility, diagnosis, and treatment and prevention of norovirus infection.

PMID- 20814449
TI  - Background Surface and Horizon Effects in the Perception of Relative Size and
      Distance.
AB  - The projected height of an object in a scene relative to a ground surface
      influences its perceived size and distance, but the effect of height should
      change when the object is moved above the horizon. In four experiments, observers
      judged relative size or relative distance for pairs of objects varying in height
      with respect to the horizon. Higher objects equal in projected size were judged
      larger below the horizon, but the relative size effect was reversed either when
      one object was on the horizon and one was above the horizon or when both objects
      were above the horizon. With the real horizon not explicitly present in the
      display, relative size judgments were affected both by the boundary of the
      visible surface and the vanishing point implied by the converging lines. For
      relative distance judgments, the higher object was judged more distant regardless
      of the height of the objects relative to the perceptual horizon, resulting in a
      reversal of the relation between size and distance judgments for objects above
      the horizon.

PMID- 20814450
TI  - Frequency-Offset Cartesian Feedback Based on Polyphase Difference Amplifiers.
AB  - A modified Cartesian feedback method called "frequency-offset Cartesian feedback"
      and based on polyphase difference amplifiers is described that significantly
      reduces the problems associated with quadrature errors and DC-offsets in classic
      Cartesian feedback power amplifier control systems.In this method, the reference
      input and feedback signals are down-converted and compared at a low intermediate
      frequency (IF) instead of at DC. The polyphase difference amplifiers create a
      complex control bandwidth centered at this low IF, which is typically offset from
      DC by 200-1500 kHz. Consequently, the loop gain peak does not overlap DC where
      voltage offsets, drift, and local oscillator leakage create errors. Moreover,
      quadrature mismatch errors are significantly attenuated in the control bandwidth.
      Since the polyphase amplifiers selectively amplify the complex signals
      characterized by a +90 degrees  phase relationship representing positive
      frequency signals, the control system operates somewhat like single sideband
      (SSB) modulation. However, the approach still allows the same modulation
      bandwidth control as classic Cartesian feedback.In this paper, the behavior of
      the polyphase difference amplifier is described through both the results of
      simulations, based on a theoretical analysis of their architecture, and
      experiments. We then describe our first printed circuit board prototype of a
      frequency-offset Cartesian feedback transmitter and its performance in open and
      closed loop configuration. This approach should be especially useful in magnetic
      resonance imaging transmit array systems.

PMID- 20814451
TI  - Thermodynamic study of (anthracene + benzo[a]pyrene) solid mixtures.
AB  - To characterize better the thermodynamic behavior of a binary polycyclic aromatic
      hydrocarbon mixture, thermochemical and vapor pressure experiments were used to
      examine the phase behavior of the {anthracene (1) + benzo[a]pyrene (2)} system. A
      solid-liquid phase diagram was mapped for the mixture. A eutectic point occurs at
      x(1) = 0.26. The eutectic mixture is an amorphous solid that lacks organized
      crystal structure and melts between T = (414 and 420) K. For mixtures that
      contain 0.10 < x(1) < 0.90, the enthalpy of fusion is dominated by that of the
      eutectic. Solid-vapor equilibrium studies show that mixtures of anthracene and
      benzo[a]pyrene at x(1) < 0.10 sublime at the vapor pressure of pure
      benzo[a]pyrene. These results suggest that the solid-vapor equilibrium of
      benzo[a]pyrene is not significantly influenced by moderate levels of anthracene
      in the crystal structure.

PMID- 20814452
TI  - Improved Resolution in Dipolar NMR Spectra Using Constant Time Evolution PISEMA
      Experiment.
AB  - The atomic structure of small molecules and polypeptides can be attained from
      anisotropic NMR parameters such as dipolar couplings (DC) and chemical shifts
      (CS). Separated local field experiments resolve DC and CS correlations into two
      dimensions. However, crowded NMR spectra represent a significant obstacle for the
      complete resolution of these anisotropic parameters. Using the PISEMA
      (Polarization Inversion Spin Exchange at the Magic Angle) experiment as a
      foundation, we designed new pulse schemes that use a constant time evolution in
      the dipolar (indirect) dimension to measure DC and CS correlations at high
      resolution. We demonstrated this approach on a 4-pentyl-4'-cyanobiphenyl (5CB)
      liquid crystal sample, achieving a resolution enhancement ranging from 30 to 60 %
      for the resonances in the dipolar dimension. These new experiments open the
      possibility of obtaining significant resolution enhancement for multidimensional
      NMR experiments carried out on oriented liquid crystalline samples as well as
      oriented membrane proteins.

PMID- 20814453
TI  - Taking psychiatry to the public in the Third World: Potential and pitfalls.

PMID- 20814454
TI  - REM sleep latency and neurocognitive dysfunction in schizophrenia.
AB  - BACKGROUND: Cognitive deficits-the hallmark of schizophrenic deterioration-still
      remain elusive as far as their pathophysiology is concerned. Various
      neurotransmitter systems have been implicated to explain these deficits.
      Abnormalities in cholinergic neurotransmission in the brain are one of the
      postulations; acetylcholine has also been postulated to regulate rapid eye
      movement (REM) sleep, especially REM latency. Thus, REM latency in patients with
      schizophrenia might provide a non-invasive window to look into the cholinergic
      functions of the brain. AIM: To study REM sleep measures and neurocognitive
      function in schizophrenia, and the changes occurring in these parameters
      following pharmacological treatment. METHODS: Thirty subjects (15 with
      schizophrenia and 15 normal non-relative controls) were evaluated in this study.
      Most patients with schizophrenia had prominent negative symptoms and deficits in
      the performance in neurocognitive tests battery. They were treated with
      antipsychotics for a variable period of time and post-treatment evaluation was
      done using the same battery of neurocognitive tests and polysomnography. Patients
      were either drug-naive or kept drug-free for at least two weeks both at baseline
      as well as at the post-treatment stage. RESULTS: A positive correlation between
      the severity of negative symptoms and neurocognitive deficits (especially on the
      Wisconsin Card Sorting), and a negative correlation between these two parameters
      and REM latency was observed. CONCLUSION: It can be hypothesized that the
      acetylcholine deficit model of dementia cannot be applied to schizophrenic
      dementia, rather a hypercholinergic state results. This state warrants
      anticholinergic medication as a treatment option for negative symptoms of
      schizophrenia.

PMID- 20814455
TI  - Cognitive dysfunction and associated factors in patients with chronic
      schizophrenia.
AB  - BACKGROUND: Deficits in neurocognitive function are a hallmark of schizophrenia.
      They are associated with clinical manifestations and the course of the illness. A
      study of cognitive dysfunction in Indian patients with schizophrenia is of
      significance in view of a more benign course and outcome of the illness in this
      region. AIM: To study cognitive deficits and associated factors in patients with
      chronic schizophrenia and compare them with those in the normal population.
      METHODS: We compared 100 patients with chronic schizophrenia with 100 matched
      normal controls on multiple measures of attention, executive function and memory.
      RESULTS: Compared to normal individuals, patients with schizophrenia performed
      poorly in all cognitive tests. Cognitive deficits in patients were related to
      gender, education, age, duration of illness, and presence of positive and
      negative symptoms. CONCLUSION: The neurocognitive profile of Indian patients with
      chronic schizophrenia resembles those of patients in developed countries.

PMID- 20814456
TI  - Stress and anxiety in parents of mentally retarded children.
AB  - BACKGROUND: Studies comparing the stress perceived by parents of mentally
      retarded and normal children are limited. AIM: (i) To find whether there exists a
      difference in the perceived stress between both the parents of mentally retarded
      children, (ii) to study whether these stresses occur more frequently in parents
      of mentally retarded children compared with those of normal children, and (iii)
      to find any correlation between the severity of perceived stressors and the
      anxiety state of these parents. METHODS: This study was conducted in the Child
      Guidance Clinic of a tertiary care psychiatry hospital. The study sample,
      comprising 180 subjects, was categorized as: group A (60 parents of profound to
      moderately mentally retarded children), group B (60 parents of mild to borderline
      mentally retarded children) and group C (60 parents of children with normal
      intelligence), which served as the control group. Each parent was evaluated using
      the Family Interview for Stress and Coping (FISC) in Mental Retardation, and the
      Hamilton Anxiety Rating Scale (HARS). RESULTS: Parents in group A had a
      significantly higher frequency of stressors and level of anxiety as compared to
      those in groups B and C. A positive correlation was found between the level of
      anxiety and stressors. CONCLUSION: Multifaceted factors made parents in groups A
      and B more vulnerable to stress compared with parents in the control group.

PMID- 20814457
TI  - Perception of burden by caregivers of patients with schizophrenia.
AB  - BACKGROUND: There is a dearth of studies assessing the burden of caregivers of
      patients with schizophrenia and illness-related variables such as age, sex,
      duration of illness, domicile, martial status, education, employment and previous
      hospitalization. AIM: The study was conducted to measure the perception of burden
      by caregivers of patients with schizophrenia and its correlation with nine
      factors on the Burden Assessment Schedule (BAS) related to spouse, physical and
      mental health, external support, caregiver's routines, support to patient,
      responsibility-taking, other relatives, patient's behaviour and caregiver's
      strategy. METHODS: Using BAS, we assessed the burden in a sample of caregivers of
      34 patients with schizophrenia taken from the OPD of the Institute of Mental
      Health and Hospital, Agra. RESULTS: A low positive correlation was found between
      urban domicile and support of the patient; of domicile Agra and effect on other
      relations; and domicile Agra and effect on the caregiver's routine. There was a
      low positive correlation between age less than 30 years and the physical and
      mental health of the caregiver, and with taking responsibility. The t test for
      population correlation was significant up to 5% probability level (p<0.05) for
      correlation between urban domicile and support of the patient; between domicile
      Agra and effect on other relations; between domicile Agra and the effect on the
      caregiver's routine; between age less than 30 years and the physical and mental
      health of the caregiver; and between age less than 30 years and taking
      responsibility. CONCLUSION: Further studies in this field are required including
      one with a non-linear correlation analytic design.

PMID- 20814458
TI  - Group meetings of caretakers of patients with schizophrenia and bipolar mood
      disorders.
AB  - BACKGROUND: In India, there is a paucity of trained professionals to execute
      psychosocial interventions. Families are thus assigned the role of primary
      caretakers of individuals with chronic mental illness. AIM: To assess the
      perceived benefits and difficulties of group meetings among caregivers of persons
      with schizophrenia and bipolar mood disorders, and to evaluate the utilization
      pattern of general hospital psychiatric unit (GHPU) services by caregivers who
      regularly attend such group meetings. METHODS: Persons with schizophrenia and
      those with bipolar mood disorders with associated psychosocial problems and on
      maintenance medication were identified at the Psychiatric Rehabilitation Unit of
      the Department of Psychiatry, Father Muller Medical College. Significant
      caregivers of the identified patients were informed about the group meeting.
      Group meetings were conducted for about 45 minutes once a month for caregivers of
      patients with schizophrenia and bipolar mood disorders. Data regarding the
      psychosocial aspects of caregivers were collected before entry to the meeting and
      after 17 months of their participation. Participants who attended the meetings
      irregularly were excluded from the study. RESULTS: The group meetings led to
      effective monitoring of the functioning of individuals, a reduction in the
      subjective family burden and family distress, a better support system with
      adequate coping skills and good compliance with treatment programmes. CONCLUSION:
      Conducting regular group meetings for a homogeneous population at a GHPU is
      feasible and beneficial.

PMID- 20814459
TI  - Assessment of the domains of quality of life in the geriatric population.
AB  - BACKGROUND: The number of studies from India on geriatric health problems,
      particularly mental health disorders and quality of life, is limited. AIM: This
      cross-sectional study was carried out in the geriatric population visiting the Dr
      T.M.A. Pai Rotary Hospital, Karkala, Karnataka. It examined the different domains
      of quality of life according to sociodemographic variables. METHODS: We studied
      70 individuals in the geriatric age group (>/=60 years) who visited the hospital
      over a period of two months from March 2003 to April 2003. The results were
      expressed in terms of mean and SE of mean. Z-test and one-way ANOVA test were
      applied to compare the mean scores of different variables under the four domains.
      A p value <0.05 was considered significant. RESULTS: The total mean score, as
      well as the mean scores in each of the four domains studied were similar in men
      and women as well as literates and illiterates. The mean scores of subjects in
      various age groups differed significantly in the domains of physical,
      psychological and social relations, while single and married subjects differed
      significantly in the domains of environmental and social relations. Overall well
      being was significantly affected in those who were single (unmarried/widowed) or
      in the age group of 60-69 years.

PMID- 20814460
TI  - Family support group in psychosocial rehabilitation.
AB  - BACKGROUND: Support groups for families of persons with mental illness are
      emerging as significant components in psychosocial rehabilitation programmes.
      AIM: To ascertain the expectations of family members who attend family support
      group meetings and to find out the efficacy of such programmes. METHODS: The data
      were collected from support group members using a semi-structured interview
      schedule. The study sample (n=20) was drawn from family members who attended the
      support group meetings regularly for a minimum period of 6 months. Data analysis
      was done using percentile. RESULTS: Analysis of the data revealed that members
      attending the support group meetings expected to get more information about the
      illness, develop skills to cope with problems at home and learn skills to deal
      with the ill person. An important finding of the study was that the members
      developed a 'feeling of togetherness' as a result of being a member of a group
      with common aims. CONCLUSION: Participation in a support group meeting positively
      affects key variables in the participant's adaptation to mental illness in a
      relative.

PMID- 20814461
TI  - Folie a deux.
AB  - Folie a deux is defined as an identical or similar mental disorder affecting two
      or more individuals, usually the members of a close family. Two case reports of
      this condition are presented with a brief review of the literature. Prompt
      recognition of this condition is an essential step in the management. The
      majority of patients with folie a deux require multiple treatments including
      separation, antipsychotics, individual and group psychotherapy, and family
      therapy.

PMID- 20814462
TI  - Paroxetine overdose.
AB  - Paroxetine is a commonly used antidepressant with a safe side-effect profile. A
      case of paroxetine overdose (560 mg) is reported in an 18-year-old female who
      attempted suicide and recovered without any sequelae, requiring only supportive
      treatment. This report highlights a case of pure paroxetine overdose and the
      safety profile of paroxetine in overdose.

PMID- 20814463
TI  - Factitious schizophrenia.
AB  - Factitious disorder is a challenging phenomenon in clinical practice. An
      inconsistent clinical picture and the presence of symptoms that do not respond to
      the seemingly appropriate treatment should alert the clinician about the
      possibility of such a diagnosis. A case of factitious psychological symptoms
      suggestive of schizophrenia is reported, and the issues of diagnosis and
      management are discussed in the light of the available literature.

PMID- 20814464
TI  - Convulsions in the treatment of obsessive-compulsive disorder.
AB  - Obsessive-compulsive disorder (OCD) and epilepsy tend to share a close
      association. However, the exact relationship between OCD symptoms and epileptic
      convulsions is not well known. A case of OCD who improved remarkably following
      drug-induced seizures is described, implicating a role for convulsion as an
      alternative therapeutic modality in OCD.

PMID- 20814465
TI  - Obsessive-compulsive disorder: An interface with possible psychotic features.

PMID- 20814466
TI  - Sexual dysfunction in India.

PMID- 20814467
TI  - Who is a good psychiatrist?-A collective view.

PMID- 20814468
TI  - Patients, doctors and the medical industry.

PMID- 20814469
TI  - Electrocardiogram interpretation skills in pediatric residents.
AB  - OBJECTIVE: The primary objective of this study was to evaluate pediatric
      residents' ability to correctly identify electrocardiogram (ECG) findings and
      pair them to a corresponding cardiac diagnosis. METHODS: Forty-six pediatric
      residents from the Johns Hopkins Children's Center were surveyed to evaluate
      their ability to interpret ECGs and factors affecting that ability. Included in
      the survey was a packet of 10 patient vignettes each accompanied by a 12-lead
      ECG. The primary outcome variable was the resident's score of correctly paired
      ECG findings with the appropriate cardiac diagnosis. One point was given for each
      pair correctly identified for a maximum of 10 points. Simple and multiple linear
      regression was used to estimate the magnitude and significance of any association
      between score of correct responses and resident year, completion of a pediatric
      cardiology rotation, self-rated ability to read ECGs, and training received in
      reading ECGs. RESULTS: The mean number of correct ECG findings and cardiac
      diagnosis pairings out of 10 for the PGY 1 group was 4.1 +/- 3, PGY 2 group 4.9
      +/- 2.9, PGY 3 group 6.6 +/- 2, and the PGY 4 group 6.8 +/- 1.7. In the
      unadjusted linear regression model, the PGY 3 group correctly identified 2.4 more
      pairings compared to the PGY 1 group (P =0.02). Those who completed a pediatric
      cardiology rotation correctly identified 2.5 more pairings compared to those who
      did not complete a rotation (P=0.001). CONCLUSIONS: ECG interpretation
      significantly improved from PGY 1 to PGY 3. Educational programs involving ECG
      interpretation should target those diagnoses with high clinical severity and
      average to poor resident knowledge.

PMID- 20814470
TI  - Veno-venous shunt-assisted cavopulmonary anastomosis.
AB  - OBJECTIVE: The bidirectional Glenn shunt is commonly performed under
      cardiopulmonary bypass for conditions that lead to a single ventricle repair. We
      report our experience of bidirectional Glenn shunt done without cardiopulmonary
      bypass. METHODS: Between June 2007 and May 2009, 186 consecutive patients
      underwent off-pump bidirectional Glenn shunt for a variety of complex cyanotic
      congenital heart defects. Age ranged from four months to six years and the median
      weight was 11.17 kg (range 4.3 - 18). After systemic heparinization, the
      procedure was done by creating a temporary shunt between the innominate vein and
      the right atrium connected across a three way connector for de-airing. Fifty one
      patients had bilateral cavae. All cases underwent complete clinical neurological
      examination. RESULTS: No case required conversion onto cardiopulmonary bypass.
      Four patients (2.14%) died in the immediate postoperative period. The mean
      internal jugular venous pressure on clamping the decompressed superior vena cava
      was 24.69 +/- 1.81 mm Hg. There was no intra-operative hemodynamic instability
      and oxygen saturation was maintained at more than 70% throughout. Post Glenn
      shunt, the saturations improved to mid 80s. Seventy four cases had documented
      forward flow across the pulmonary valve. The mean duration of ventilation was
      10.17 +/- 8.96 hours and there were no neurological complications. Six patients
      (3.22%) developed pleural effusions, 4 patients (2.15%) had nodal rhythm and 9
      patients (4.83%) had superficial sternal wound infection. CONCLUSIONS: Our
      results show that off-pump bidirectional Glenn shunt can be done safely in
      patients not requiring associated intra-cardiac correction. It avoids
      cardiopulmonary bypass and its related complications, is economical and
      associated with excellent results. In our opinion, this is the largest series of
      off-pump bidirectional Glenn shunt in the literature.

PMID- 20814471
TI  - Clinico-morphological correlations in the categorization of holes between the
      ventricles.
AB  - Controversy still exists in the categorization of holes between the ventricles,
      although they are the most common congenital cardiac malformation. Advanced
      imaging techniques such as three-dimensional echocardiography and computed
      tomographic angiography offer superb anatomical details of these defects. In this
      review, we have sought to collate the features highlighted in different
      categorizations and identify their similarities, but also emphasize their
      differences. We hope that an analysis of this type, now achievable during life,
      using advanced imaging, might lead to the appearance of a unified system for
      diagnosis and description of holes between the ventricles.

PMID- 20814472
TI  - Transhepatic approach for rehabilitation of stenosed pulmonary arteries.
AB  - Transhepatic cardiac catheterization and intervention is used in selected cases
      in our institution. A retrospective review of transcatheter interventions for the
      pulmonary artery was conducted. Forty-five transhepatic procedures were
      performed. Thirteen involved intervention, to rehabilitate the branch pulmonary
      arteries. The median weight of the patients was 9.9 Kg +/- 3.4. The patients' age
      ranged from eight months to 86 months (median 23 months). The largest sheath used
      was 7F. All the patients underwent success intervention with no complication
      related either to the transhepatic approach or the intervention. The branch
      pulmonary artery diameter increased from 4.5 +/- 2.2 mm to 7 +/- 3 mm. Most of
      the procedures were performed under conscious sedation / deep sedation protocol.
      Hemostasis was achieved in all patients by gradual sheath withdrawal, followed by
      application of upward pressure on the tract from the subcostal area. In the
      absence of patent femoral veins the transhepatic approach can be used to perform
      successful and safe interventions, to rehabilitate the pulmonary artery system.
      It may offer the additional advantage of using larger sheaths than would be felt
      appropriate for the femoral veins.

PMID- 20814473
TI  - Oral anticoagulants in pediatric cardiac practice: A systematic review of the
      literature.
AB  - Recent advances in the pediatric heart surgery, especially the Fontan procedure,
      has necessitated an increased use of oral anticoagulants in pediatric cardiac
      patients. Warfarin is the standard agent used for most pediatric indications,
      though there are very few randomized control studies in children regarding its
      use. This review summarizes the current indications and evidence base regarding
      the use of oral anticoagulants in the pediatric age group.

PMID- 20814474
TI  - Patent foramen ovale closure.

PMID- 20814475
TI  - Establishing a pediatric cardiac intensive care unit - Special considerations in
      a limited resources environment.
AB  - Pediatric cardiac intensive care has evolved as a distinct discipline in well
      established pediatric cardiac programs in developed nations. With increasing
      demand for pediatric heart surgery in emerging economies, a number of new
      programs are being established. The development of robust pediatric cardiac
      intensive care units (PCICU) is critical to the success of these programs.
      Because of substantial resource limitations existing models of PCICU care cannot
      be applied in their existing forms and structure. A number of challenges need to
      be addressed to deliver pediatric cardiac intensive care in the developing world.
      Limitations in infrastructure, human, and material resources call for a number of
      innovations and adaptations. Additionally, a variety of strategies are required
      to minimize costs of care to the individual patient. This review provides a
      framework for the establishment of a new PCICU program in face of resource
      limitations typically encountered in the developing world and emerging economies.

PMID- 20814476
TI  - Diaphragmatic palsy after cardiac surgical procedures in patients with congenital
      heart.
AB  - Paralysis of diaphragm on one or, exceptionally, both sides is a common cause of
      delayed recovery and excessive morbidity following pediatric cardiac surgery. The
      consequences of this complication after all forms of congenital heart surgery in
      newborns and young infants can be potentially serious. The impact of
      diaphragmatic palsy on the physiology after single ventricle palliations is
      particularly significant. It is necessary for all professionals taking care of
      children with heart disease to be familiar with the etiology, diagnosis, and
      management of this condition. Early recognition and prompt management of
      diaphragmatic palsy can potentially reduce the duration of mechanical ventilation
      and intensive care in those who develop this complication. This review summarizes
      the anatomy of the phrenic nerves, reasons behind the occurrence of diaphragmatic
      palsy, and suggests practical guidelines for management.

PMID- 20814477
TI  - Pleural effusions in children undergoing cardiac surgery.
AB  - Persistent pleural effusions are a source of significant morbidity and mortality
      following surgery in congenital heart disease. In this review, we discuss the
      etiology, pathophysiology, and management of this common complication.

PMID- 20814478
TI  - Multiple coil closure of isolated aortopulmonary collateral.
AB  - A 7-month-old girl was diagnosed to have large aortopulmonary collateral during
      evaluation for congestive heart failure. There was no other evidence of
      cardiopulmonary disease. The collateral was successfully closed with multiple
      coils delivered sequentially. We describe the issues associated during closure of
      the aortopulmonary collateral in this case. To the best of our knowledge, this is
      the first reported case of large aortopulmonary collateral presenting with heart
      failure in an otherwise structurally normal heart that was closed successfully
      with multiple coils delivered sequentially.

PMID- 20814479
TI  - Hybrid management of a large atrial septal defect and a patent ductus arteriosus
      in an infant with chronic lung disease.
AB  - We report a case wherein a dysmorphic four-month-old infant (weighing 4.5 kgs)
      with an 8 mm atrial septal defect (ASD), a 1.5 mm patent ductus arteriosus (PDA),
      a 2 mm mid-muscular ventricular septal defect (VSD) associated with chronic lung
      disease, and severe pulmonary hypertension, was successfully managed using a
      hybrid approach, without the use of cardiopulmonary bypass (CPB). Through a
      median sternotomy, the PDA was ligated and the ASD was closed with a 9 mm
      Amplatzer septal occluder implanted through peratrial access. The VSD was left
      untouched. Serial echocardiograms showed complete closure of the ASD and PDA,
      with progressive normalization of the pulmonary artery (PA) pressures within
      three months. The child rapidly gained weight and was weaned from sildenafil and
      oxygen administration. After 12 months, the VSD closed spontaneously and the
      child remained well, with normal PA pressures. A hybrid approach without the use
      of CPB should be considered in the management of infants with congenital heart
      disease, associated with chronic lung disease and pulmonary hypertension.

PMID- 20814480
TI  - Hybrid palliation of interrupted aortic arch in a high-risk neonate.
AB  - We report a case of a high-risk neonate with interrupted aortic arch (IAA) and
      ventricular septal defect who underwent a successful hybrid palliative procedure
      using a ductal stent and bilateral branch pulmonary artery banding. This case
      represents not only a successful use of hybrid approach in high-risk neonates
      with IAA, but also introduces an alternative and safe access for ductal stent
      insertion through the right ventricular infundibulum.

PMID- 20814481
TI  - Balloon atrial septostomy through internal jugular vein in a 45-day-old child
      with transposition of great arteries.
AB  - Balloon atrial septostomy is a common palliative procedure in D-transposition of
      great arteries. It is technically easy before 2-3 weeks of age when the septum
      primum is thin. Femoral vein or umbilical vein, when available, is the common
      access used for this procedure. In situations when these accesses are not
      available or in case of inferior vena cava interruption, trans-hepatic access is
      used. Internal jugular vein (IJV) access is not used as it is difficult to enter
      the left atrium through this route. We describe a case of successful Balloon
      atrial septostomy done through IJV in a 45-day-old child with emphasis on the
      technique, hardware and precautions necessary during the procedure.

PMID- 20814482
TI  - Ductal aneurysm masquerading as nonresolving pneumonia: A challenging
      differential!
AB  - We report here, the case of a six-and-a-half-month-old boy investigated for
      persistent respiratory distress and homogeneous opacity in the left upper lobe.
      Echocardiography revealed a giant ductal aneurysm compressing the left pulmonary
      artery and upper lobe division of the left bronchus. Computerized tomography
      angiogram delineated the exact anatomy and prompt surgical resection provided a
      successful cure to this lesser known entity.

PMID- 20814483
TI  - Successful retrieval of migrated Amplatzer septal occluder.
AB  - Migration and embolization of the Amplatzer septal occluder (ASO) have been
      reported. However, there is only limited information on the methods of systematic
      retrieval of these devices. In this report, we describe the a case of a 4 year
      old girl who underwent closure of her atrial septal defect (ASD) using a 17 mm
      ASO. The device migrated in to the right atrium an anteroposterior plane 24 hours
      later with a resultant residual shunt. The device was successfully retrieved
      percutaneously and the ASD was closed using a 20 mm ASO.

PMID- 20814484
TI  - A rare case of double orifice mitral valve with perimembranous ventricular septal
      defect: Application of three-dimensional echocardiography for clinical decision
      making.
AB  - Double orifice mitral valve (DOMV) is an uncommon anomaly of surgical importance
      characterized by a mitral valve with a single fibrous annulus with two orifices
      opening into the left ventricle (LV). Subvalvular structures, especially the
      tensor apparatus, invariably show various degrees of abnormality. Associated
      congenital heart defects are common, though DOMV can occur as an isolated
      anomaly. Two-dimensional echocardiography is useful for diagnosis but combining
      it with real-time three-dimensional echocardiography helps in a more detailed
      evaluation of mitral valve and subvalvular structures as is shown in this case
      description.

PMID- 20814485
TI  - Pulmonary edema following transcatheter closure of atrial septal defect.
AB  - Pulmonary edema after device closure of atrial septal defect (ASD) is a rare
      complication. We present illustrative images of a case of pulmonary edema after
      device closure of ASD in a 53 year old adult. Older patients undergoing ASD
      closure can benefit from their left atrial and left ventricular end diastolic
      pressures measurement before and after temporary balloon occlusion of ASD.

PMID- 20814486
TI  - Klippel Feil syndrome with isolated hypokinesia of the left ventricle: A rare
      association.

PMID- 20814487
TI  - Cardiac Candida krusei infection.

PMID- 20814488
TI  - Genomics, genetic engineering and artificial cells.

PMID- 20814489
TI  - The role of infections in the pathogenesis and course of multiple sclerosis.
AB  - Interplay between susceptibility genes and environmental factors is considered
      important player in the genesis of multiple sclerosis (MS). Among environmental
      factors, a role for an infectious pathogen has long been considered central to
      the disease process. This opinion has support both from epidemiological data and
      the findings of immunological abnormalities in spinal fluid that reflect an
      immune response to an as yet undetermined antigen, possibly a pathogen, in the
      cerebrospinal fluid. Our review will outline the current understanding of the
      role of infection in the causation and progression of MS. We will review the data
      that point to an infectious cause of MS and consider the specific agents
      Chlamydophila (Chlamydia) pneumoniae, Human Herpes Virus 6, and Epstein-Barr
      Virus, that are implicated in either the development or progression of MS.

PMID- 20814490
TI  - Epilepsy surgery: recommendations for India.
AB  - The following article recommends guidelines for epilepsy surgery for India. This
      article reviews the indications, the various surgical options available and the
      outcome of surgery for drug resistant epilepsy based on current evidence.
      Epilepsy surgery is a well-established option for patients who have been
      diagnosed to have drug resistant epilepsy (DRE) (on at least two appropriate,
      adequate anti-epileptic drugs (AEDs) (either in monotherapy or in combination)
      with continuing seizures), where the presurgical work-up has shown concordance of
      structural imaging (magnetic resonance imaging) and electrical mapping data
      (electroencephalography (EEG), video EEG). There may be a requirement of
      functional imaging techniques in a certain number of DRE like positron emission
      tomography (PET), single photon emission tomography, (SPECT)). Invasive
      monitoring should be restricted to a few when all noninvasive investigations are
      inconclusive, there is a dual pathology or there is a discordance of noninvasive
      data. The types of surgery could be curative (resective surgeries: amygdalo
      hippocampectomy, lesionectomy and multilobar resections; functional surgeries:
      hemispherotomy) and palliative (multiple subpial transaction, corpus callosotomy,
      vagal nerve stimulation). Epilepsy surgery in indicated cases has a success range
      from 50 to 86% in achieving seizure freedom as compared with <5% success rate
      with AEDs only in persons with DRE. Centers performing surgery should be
      categorized into Level I and Level II.

PMID- 20814491
TI  - Diagnosis and treatment of chronic insomnia.
AB  - Insomnia is a disorder characterized by inability to sleep or a total lack of
      sleep, prevalence of which ranges from 10 to 15% among the general population
      with increased rates seen among older ages, female gender, White population and
      presence of medical or psychiatric illness. Yet this condition is still under
      recognized, under-diagnosed, and under-treated. This article aims to review the
      operational definitions and management of chronic insomnia. A computerized search
      on PubMed carried from 1980 to January 2009 led to the summarization of the
      results. There are several strategies to manage chronic insomnia. To initiate
      treatment, it is necessary to define it and differentiate it from other co-morbid
      psychiatric disorders. Non-pharmacologic strategies such as stimulus control
      therapy and relaxation and cognitive therapies have the best effect sizes
      followed by sleep restriction, paradoxical intention and sleep hygiene education
      which have modest to less than modest effect sizes. Among pharmacotherapeutic
      agents, non-benzodiazepine hypnotics are the first line of management followed by
      benzodiazepines, amitryptiline and antihistaminics. However, adequate trials of
      combined behavior therapy and pharmacotherapy are the best course of management.

PMID- 20814492
TI  - Psychomotor seizures, Penfield, Gibbs, Bailey and the development of anterior
      temporal lobectomy: a historical vignette.
AB  - Psychomotor seizures, referred to as limbic or partial complex seizures, have had
      an interesting evolution in diagnosis and treatment. Hughlings Jackson was the
      first to clearly relate the clinical syndrome and likely etiology to lesions in
      the uncinate region of the medial temporal lobe. With the application of
      electroencephalography (EEG) to the study of human epilepsy as early as 1934 by
      Gibbs, Lennox, and Davis in Boston, electrical recordings have significantly
      advanced the study of epilepsy. In 1937, Gibbs and Lennox proposed the term
      "psychomotor epilepsy" to describe a characteristic EEG pattern of seizures
      accompanied by mental, emotional, motor, and autonomic phenomena. Concurrently,
      typical psychomotor auras and dreamy states were produced by electrical
      stimulation of medial temporal structures during epilepsy surgery by Penfield in
      Montreal. In 1937, Jasper joined Penfield, EEG was introduced and negative
      surgical explorations became less frequent. Nevertheless, Penfield preferred to
      operate only on space occupying lesions. A milestone in psychomotor seizure
      diagnosis was in the year 1946 when Gibbs, at the Illinois Neuropsychiatric
      Institute, Chicago, reported that the patient falling asleep during EEG was a
      major activator of the psychomotor discharges and electrographic ictal episodes
      becoming more prominently recorded. Working with Percival Bailey, Gibbs was
      proactive in applying EEG to define surgical excision of the focus in patients
      with intractable psychomotor seizures. By early 1950s, the Montreal group began
      to clearly delineate causative medial temporal lesions such as hippocampal
      sclerosis and tumors in the production of psychomotor seizures.

PMID- 20814493
TI  - Neuropsychiatric manifestations of systemic lupus erythematosus: Iranian
      experience.
AB  - AIMS: To evaluate the prevalence and characteristics of different neurological
      and psychiatric presentations in patients admitted to hospital with systemic
      lupus erythematosus (SLE). MATERIALS AND METHODS: In this retrospective hospital
      based study, we examined the medical records of patients with SLE who were
      referred to the hospitals affiliated to Shiraz University of Medical Sciences
      from 1995 to 2005. All patients of SLE who had clinical neurological or
      psychiatric features were included in this study. The patients demographic data,
      findings on general examination, neuropsychiatric manifestations, and the results
      of laboratory investigations and imaging studies were recorded. Clinical
      manifestations were classified according to the American College of Rheumatology
      (ACR) case definitions. RESULTS: Of the 407 study patients, 11.3% had
      neuropsychiatric complications. The most frequent findings were seizure (63%),
      headache (60%), and decreased level of consciousness (50%). Cerebrovascular
      disease (28.3%), seizure disorder (26.5%), and acute confusional state (19.6%)
      were the most prevalent syndromes. CONCLUSION: The prevalence and nature of
      different neurological presentations of SLE in Iranian patients has some
      similarities to that seen in other populations, as well as some differences.
      Ethnic and environmental factors may contribute to these differences.

PMID- 20814494
TI  - Fungal infections of the central nervous system in HIV-negative patients:
      experience from a tertiary referral center of South India.
AB  - OBJECTIVE: To describe the clinical, radiological, and cerebrovascular fluid
      (CSF) findings and the outcome of microbiologically or histopathologically proven
      fungal infections of the central nervous system (CNS) in HIV-negative patients.
      METHODOLOGY AND RESULTS: We identified definite cases of CNS mycosis by screening
      the medical records of our institute for the period 2000-2008. The clinical and
      imaging details and the outcome were abstracted from the medical records and
      entered in a structured proforma. There were 12 patients with CNS mycosis (i.e.,
      2.7% of all CNS infections treated in this hospital); six (50%) had cryptococcal
      infection, three (25%) had mucormycosis, and two had unclassified fungal
      infection. Four (33%) of them had diabetes as a predisposing factor. The common
      presentations were meningoencephalitis (58%) and polycranial neuritis (41%).
      Magnetic resonance imaging revealed hydrocephalus in 41% and meningeal
      enhancement in 25%, as well as some unusual findings such as subdural hematoma in
      the bulbocervical region, carpeting lesion of the base of the skull, and
      enhancing lesion in the cerebellopontine angle. The CSF showed pleocytosis (66%),
      hypoglycorrhachia (83%), and elevated protein levels (100%). The diagnosis was
      confirmed by meningocortical biopsy (in three cases), paranasal sinus biopsy (in
      four cases), CSF culture (in three cases), India ink preparation (in four cases),
      or by cryptococcal polysaccharide antigen test (in three cases). Out of the ten
      patients for whom follow-up details were available, six patients recovered with
      antifungal medications (amphotericin B, 1 mg/kg/day for the minimum period of 6
      weeks) and/or surgical treatment. Four patients expired (only one of them had
      received antifungal therapy). CONCLUSIONS: Most patients with CNS mycosis recover
      with appropriate therapy, but the diagnosis and management of these rare
      infections remains a challenge to clinicians.

PMID- 20814495
TI  - Qualitative aspects of learning, recall, and recognition in dementia.
AB  - OBJECTIVE: To determine whether learning and serial position effect (SPE) differs
      qualitatively and quantitatively among different types of dementia and between
      dementia patients and controls; we also wished to find out whether interference
      affects it. MATERIALS AND METHODS: We administered the Malayalam version of the
      Rey Auditory Verbal Learning Test (RAVLT) to 30 cognitively unimpaired controls
      and 80 dementia patients [30 with Alzheimer's disease (AD), 30 with vascular
      dementia (VaD), and 20 with frontotemporal dementia (FTD)] with mild severity on
      the Clinical Dementia Rating Scale. RESULTS: All groups were comparable on
      education and age, except the FTD group, who were younger. Qualitatively, the
      learning pattern and SPE (with primacy and recency being superior to
      intermediate) was retained in the AD, VaD, and control groups. On SPE in free
      recall, recency was superior to intermediate in the FTD group (P < 0.01 using
      Bonferroni correction). On recognition, the AD and VaD groups had more misses (P
      < 0.01), while the FTD group had more false positives (P < 0.01). CONCLUSION:
      Quantitative learning is affected by dementia. The pattern of qualitative
      learning remains unaltered in dementia in the early stages.

PMID- 20814497
TI  - Role of the BACTEC radiometric method in the evaluation of patients with
      clinically probable tuberculous meningitis.
AB  - BACKGROUND: Confirmation of tuberculous meningitis (TBM) and initiation of
      treatment are often delayed due to limitations in isolating Mycobacterium
      tuberculosis from cerebrospinal fluid (CSF). OBJECTIVES: To evaluate the role of
      the BACTEC radiometric method in a clinical setting for the early diagnosis of
      TBM. MATERIALS AND METHODS: Patients meeting criteria for clinically probable TBM
      over a 3 year period were included. Clinical features, results of CSF
      investigations (protein, glucose, cell count, Ziehl-Neelsen staining, culture in
      Lowenstein-Jensen (LJ) medium and BACTEC) and brain CT imaging were reviewed.
      Drug sensitivity was tested using BACTEC. Patients were started on standard
      treatment and functional outcome, and response at discharge and follow-up were
      assessed. Patients were divided according to whether or not M. tuberculosis was
      isolated by BACTEC and the clinical, radiological, and laboratory features
      compared. RESULTS: Sixty patients were evaluated. The mean age was 30 years +/-
      11.7 years. Headache and fever were the most common symptoms and the mean
      duration was 26 days. CT findings were hydrocephalus (n=21), basal exudates
      (n=16), and tuberculoma (n=14). In 40 patients, M. tuberculosis was isolated by
      BACTEC and average 15 days was required for detection, whereas it was 30 days in
      LJ medium. Results of drug-sensitivity testing (n=32) were obtained average 7
      days after isolation. Patients from whom M. tuberculosis had been isolated by
      BACTEC more often had tuberculomas in CT imaging (P=0.018). CONCLUSION: Use of
      the BACTEC method allows early confirmation in patients with clinically probable
      TBM. It can guide clinicians in the rational use of anti-tuberculosis treatment
      by confirming diagnosis and identifying drug- sensitivity.

PMID- 20814496
TI  - Post-stroke depression: prevalence and relationship with disability in chronic
      stroke survivors.
AB  - OBJECTIVES: To evaluate (1) the prevalence of operationally defined depressive
      disorder (ICD-10) in chronic stroke subjects and (2) the relationship of post
      stroke depression (PSD) with disability. DESIGN: Cross-sectional, descriptive
      study. SETTING: Neurological rehabilitation unit of a tertiary care university
      research center. MATERIALS AND METHODS: Participants were those with first
      episode of supratentorial stroke of more than 3 months' duration with impaired
      balance and gait who had been referred for rehabilitation. Data were collected on
      demographic data, stroke data (side and type of lesion and post-stroke duration),
      cognition (mini mental state examination), depressive ideation (Hamilton
      Depression Rating Scale - HRDS), impairment (Scandinavian Stroke Scale), balance
      (Berg Balance Scale), ambulatory status (Functional Ambulation Category), walking
      ability (speed), and independence in activities of daily living (Barthel Index).
      Statistical analysis was done using SPSS 13.0. We carried out the chi-square test
      for ordinal variables and the independent t test for continuous variables.
      RESULTS: Fifty-one patients (M:F: 41:10) of mean age 46.06 +/- 11.19 years and
      mean post-stroke duration of 467.33 +/- 436.39 days) were included in the study.
      Eighteen of the 51 participants (35.29%) met the criteria for depression.
      Demographic variables like male gender, being married, living in a nuclear
      family, urban background, and higher HRDS score were significantly correlated
      with PSD (P < 0.05). Depression was related to functional disability after stroke
      but to a statistically insignificant level (P > 0.05) and was unrelated to lesion
      related parameters. CONCLUSION: Depression occurs in one-third of chronic stroke
      survivors and is prevalent in subjects referred for rehabilitation. PSD is
      related primarily to demographic variables and only to a lesser extent to
      functional disability following stroke.

PMID- 20814498
TI  - Beta-interferons in multiple sclerosis: a single center experience in India.
AB  - BACKGROUND: Indian-Asian multiple sclerosis behaves somewhat differently from
      Western disease. It is not known if the response to beta-interferon is also
      different. AIM: To demonstrate the decrease in relapses with beta-interferon in
      Indian patients with multiple sclerosis. PATIENTS AND METHODS: Patients with
      relapsing-remitting or secondary progressive multiple sclerosis with at least two
      relapses were started on beta-interferon. RESULTS: Sixteen patients were followed
      up for a period of 1-3 years. Fifteen had relapsing-remitting multiple sclerosis
      (MS). The mean number of relapses in these patients before interferons were
      started was 3.4. The mean yearly relapse rate was 1.3. The mean Kurtzke Expanded
      Disability Status Scale (EDSS) at the start of beta-interferon therapy in
      relapsing-remitting MS was 1.7. Ten of these patients were on Avonex((R))
      (interferon beta1a) and six (including the patient with secondary progressive MS)
      were on Betaferon((R)) (interferon beta1b). On follow-up, three patients (two on
      Avonex((R)) and one on Betaferon((R)) ) had relapses. The respective beta
      interferon being received by these patients was continued, with no further
      relapses. The remaining patients had no relapse or clinical or MRI progression
      after starting the drug. The side effect profile of the drug in these patients
      was favorable; although nearly all developed fever on the first day of the
      injection, only 50% of the patients continued to have fever after 3 months. Two
      patients developed psychiatric symptoms, requiring discontinuation of the drug.
      CONCLUSION: Our prospective follow-up study shows that beta-interferons are safe
      and effective in Indian patients with relapsing-remitting or secondary
      progressive MS.

PMID- 20814499
TI  - Idiopathic CD4 lymphocytopenia presenting as refractory cryptococcal meningitis.
AB  - Idiopathic CD4 T-lymphocytopenia (ICL) is a syndrome characterized by depletion
      of CD4 T-cells without evidence of human immunodeficiency virus (HIV) infection.
      There are a few reported cases of ICL associated with different diseases and
      clinical conditions, most commonly the opportunistic infections like
      Tuberculosis, fungal and parasitic diseases which are also seen in HIV-positive
      patients. We report a case without risk factors or laboratory evidence of HIV
      infection who presented with refractory cryptococcal meningitis and was found to
      have ICL.

PMID- 20814500
TI  - Repetitive compound muscle action potentials in electrophysiological diagnosis of
      congenital myasthenic syndromes: a case report and review of literature.
AB  - Congenital myasthenic syndromes (CMSs) are a heterogeneous group of disorders,
      characterized by dysfunction of neuromuscular junction (NMJ) transmission. These
      syndromes are genetically inherited and are present since birth. Some have
      characteristic clinical or electrodiagnostic features but in many cases
      determination of the specific form requires genetic studies or specialized
      morphological and electrophysiological studies on muscle tissue. We report a case
      of a 4-year-old boy with progressive ptosis and limitation of ocular movements
      who was diagnosed as slow-channel CMS based on the characteristic
      electrodiagnostic features. Repetitive compound muscle action potentials (R
      CMAPs) were recorded after single nerve stimulus, with decremental response after
      repetitive trains performed at 3 Hz. CMSs are at times clinically difficult to
      distinguish from acquired myasthenia. The characteristic clinical and
      electrodiagnostic features help in the diagnosis and enable rational therapy. In
      this article we discuss the characteristics of synaptic R-CMAPs.

PMID- 20814501
TI  - Familial amyloidotic polyneuropathy with muscle, vitreous, leptomeningeal, and
      cardiac involvement: phenotypic, pathological, and MRI description.
AB  - Familial amyloidotic polyneuropathy (FAN type 1) is a rare systemic disease that
      causes severe and disabling peripheral neuropathy. We describe the phenotypic,
      radiological, and pathological characteristics of a patient with familial amyloid
      polyneuropathy type 1 who had evidence of motor-sensory-autonomic neuropathy,
      ocular vitreous deposits, diffuse leptomeningeal involvement, and hypertrophic
      cardiomyopathy. Muscle involvement, an infrequently reported feature, was also
      observed. Early recognition of the disease has significant therapeutic
      implications.

PMID- 20814502
TI  - Valproate-induced hyperammonemic encephalopathy enhanced by topiramate and
      phenobarbitone: a case report and an update.
AB  - Although sodium valproate (VPA)-induced hepatic encephalopathy is a well
      recognized entity, VPA can occasionally produce encephalopathy secondary to
      hyperammonemia in the presence of normal hepatic function, namely valproate
      induced non-hepatic hyperammonemic encephalopathy (VNHE). Known risk factors
      include therapy with multiple antiepileptic drugs, especially when topiramate is
      one of the drugs; presence of underlying inborn errors of metabolism; febrile
      states; and insufficient nutritional intake. We describe a 5-year-old male child
      who developed VNHE while on polypharmacy with topiramate and phenobarbitone; the
      child also had poor nutritional intake. The encephalopathy reversed with
      withdrawal of VPA and treatment with L-carnitine. We emphasize the need for early
      recognition, investigation, and treatment of this potentially life-threatening
      condition. We also recommend that VPA, topiramate, and phenobarbitone should not
      be given in combination.

PMID- 20814503
TI  - Internal carotid artery dissection: an unusual cause of occipital infarction.

PMID- 20814504
TI  - Hemi-capsulo-rhombencephalic demyelination.

PMID- 20814506
TI  - Immunoglobulins as steroid sparing agents in chronic relapsing inflammatory optic
      neuropathy.

PMID- 20814508
TI  - Ergonomics in laparoscopic surgery.
AB  - Laparoscopic surgery provides patients with less painful surgery but is more
      demanding for the surgeon. The increased technological complexity and sometimes
      poorly adapted equipment have led to increased complaints of surgeon fatigue and
      discomfort during laparoscopic surgery. Ergonomic integration and suitable
      laparoscopic operating room environment are essential to improve efficiency,
      safety, and comfort for the operating team. Understanding ergonomics can not only
      make life of surgeon comfortable in the operating room but also reduce physical
      strains on surgeon.

PMID- 20814509
TI  - 'Stepped procedure' in laparoscopic cyst decortication during the learning period
      of laparoscopic surgery: Detailed evaluation of initial experiences.
AB  - BACKGROUND: We evaluated the importance and efficacy of 'stepped procedure' in
      laparoscopic cyst decortication as an initial experience in it. MATERIALS AND
      METHODS: A 36 renal cyst cases were included. The stepped retroperitonoscopic
      cyst excision divided into three groups. First step, doing the incisions to place
      the ports and expanding the retroperitoneal space with balloon distension, second
      step, placement of trocars and reach to the cyst, third step, aspiration and
      decortication of the cyst. The difficulty of the sessions was measured with the
      Visual Analog Scale (VAS) scoring system. Score was determined according to the
      difficulty of the surgical step ranging from '0' to '10', '0', too easy, '10' too
      difficult'. The durations were measured. One-way ANOVA test was used for
      statistical analysis. RESULTS: The mean age was 52.0 (20-75) years. The mean
      operation time was 52.0 min. The mean duration of the first step was 12.5,
      second, 26.0 and third, 22.5 min. The mean VAS of first step, 3.2, second, 6.0
      and third, 3.6 There were only significant differences in duration time and VAS
      score for second step among the surgeons (P<0.05). CONCLUSIONS: Laparoscopic cyst
      decortication may provide gaining experience to approach the kidney
      laparoscopically. The side, size and localization of cysts were not found
      associated with the difficulty of the method.

PMID- 20814510
TI  - Retrospective evaluation of patients of gastroesophageal reflux disease treated
      with laparoscopic Nissen's fundoplication.
AB  - AIMS: To evaluate retrospectively the outcome of laparoscopic fundoplication in a
      cohort of patients with typical symptoms of gastroesophageal reflux disease
      (GERD). MATERIALS AND METHODS: Forty-two patients with typical symptoms of GERD,
      who were operated for laparoscopic Nissen's fundoplication from March 2001 to
      August 2008, were studied. The study was limited to patients with positive
      findings on upper gastrointestinal (GI) endoscopy done by us and "typical"
      symptoms (heartburn, regurgitation, and dysphagia) of GERD. Laparoscopic Nissen's
      fundoplication was performed when clinical assessment suggested adequate
      oesophageal motility and length. Only one patient who had negative endoscopic
      findings underwent a 24-h pH monitoring before surgery. Outcome measures included
      assessment of the relief of the primary symptom responsible for surgery in the
      early postoperative period; the patient's evaluation of outcome, and quality of
      life after surgery. RESULTS: Relief of the primary symptom responsible for
      surgery was achieved in 95.24% of patients at a mean follow-up of 28 months.
      Thirty-five patients were asymptomatic, two had minor gastrointestinal symptoms
      not requiring medical therapy, three patients had gastrointestinal symptoms
      requiring medical therapy/Proton Pump Inhibitors (PPI) and in two patients the
      symptoms worsened after surgery. There were no deaths. Clinically significant
      complications occurred in six patients. Median hospital stay was 3 days,
      decreasing from 6 days in the first 10 patients to 3 days in the last 10
      patients. CONCLUSIONS: Laparoscopic Nissen's fundoplication is the choice of
      operation for clinically symptomatic GERD patients.

PMID- 20814511
TI  - Laparoscopic Heller's cardiomyotomy in cirrhosis with oesophageal varices.
AB  - Surgical intervention in cirrhosis of liver with portal hypertension is
      associated with increased morbidity and mortality. This is attributed to liver
      decompensation, intra-operative bleeding, prolonged operative time, wound related
      and anaesthesia complications. Laparoscopic surgery in cirrhosis is advantageous
      but is associated with technical challenges. We report one such case of hepatitis
      C cirrhosis with oesophageal varices and symptomatic achalasia cardia, who was
      successfully treated by laparoscopic cardiomyotomy after thorough preoperative
      workup and planning. In the review of literature on pubmed, no such case is
      reported.

PMID- 20814512
TI  - Urinary ascites secondary to delayed diagnosis of laparoscopic bladder injury.
AB  - We present a case of urinary ascites in a young woman secondary to unrecognized
      bladder injury during gynaecologic laparoscopic surgery. Delayed diagnosis
      occurred due to the absence of expected changes in serum biochemistry, which made
      the diagnosis of urinoma less likely. High suspicion of bladder injury following
      laparoscopic surgery should be present in patients with ill-defined symptoms even
      if no biochemical changes are seen. The case demonstrates important points in
      relation to the consequences of delayed diagnosis as well as overview on
      detection and prevention of such injury.

PMID- 20814513
TI  - Laparoscopic transperitoneal pyelopyelostomy and ureteroureterostomy of
      retrocaval ureter: Report of two cases and review of the literature.
AB  - We report two cases of retrocaval ureter that were successfully treated by a
      laparoscopic transperitoneal approach. Presentation of both these cases was with
      flank pain. Ureteroureterostomy using an intracorporeal suture technique was
      performed for one, and pyelopyelostomy for the other case. Operative time was 120
      min and 110 min, respectively. Pyelopyelostomy was technically easier to perform
      than ureteroureterostomy that required an extra fourth port insertion to
      facilitate dissection. With increasing experience with the intracorporeal
      suturing laparoscopic technique of either pyelopyelostomy or ureteroureterostomy
      should be the first choice for retrocaval ureter.

PMID- 20814514
TI  - Concomitant laparoscopic urological procedures - Does it contribute to morbidity?

PMID- 20814516
TI  - Editorial.

PMID- 20814515
TI  - Concomitant laparoscopic procedures can be done for urological diseases.

PMID- 20814517
TI  - Exploring larger evidence-base for contemporary Ayurveda.

PMID- 20814518
TI  - A comparative pharmacological investigation of three samples of 'Guduchi ghrita'
      for adaptogenic activity against forced swimming induced gastric ulceration and
      hematological changes in albino rats.
AB  - This study was undertaken to investigate the impact of formulation factors and
      adjuvants on the expression of biological activity of Tinospora cordifolia
      (Willd.) Miers. The adaptogenic effect of three samples of Guduchi ghrita,
      prepared using plain ghee (clarified butter) obtained from three different
      sources was studied in albino rats and compared with expressed juice of stem of
      Guduchi. The test preparations were evaluated against forced-swimming induced
      hypothermia, gastric ulceration and changes in the hematological parameters. The
      test drug given in the form of 'ghrita' produced better effect in comparison to
      the expressed juice. Among the three 'ghrita' preparations evaluated, only the
      'Solapur Guduchi ghrita' (SGG) was found to produce significant inhibition of
      stress hypothermia and gastric ulceration. The other two preparations 'Nanded
      Guduchi ghrita' (NGG), and 'Wardha Guduchi ghrita' (WGG) could produce only a
      marginal effect. In hematological parameters 'Guduchi' juice produced better
      reversal of the stress-induced changes in comparison to the test 'ghrita'
      preparations. The present study provides evidence highlighting the importance of
      formulation factors for the expression of biological activity.

PMID- 20814519
TI  - A comparative study of Barron's rubber band ligation with Kshar Sutra ligation in
      hemorrhoids.
AB  - Despite a long medical history of identification and treatment, hemorrhoids still
      pose a challenge to the medical fraternity in terms of finding satisfactory cure
      of the disease. In this study, Kshar Sutra Ligation (KSL), a modality of
      treatment described in Ayurveda, was compared with Barron's Rubber Band Ligation
      (RBL) for grade II and grade III hemorrhoids. This study was conducted in 20
      adult patients of either sex with grade II and grade III hemorrhoids at two
      different hospitals. Patients were randomly allotted to two groups of 10 patients
      each. Group I patients underwent RBL, whereas patients of group II underwent KSL.
      Guggul-based Apamarga Kshar Sutra was prepared according to the principles laid
      down in ancient Ayurvedic texts and methodology standardized by IIIM, Jammu and
      CDRI, Lucknow. Comparative assessment of RBL and KSL was done according to 16
      criteria. Although the two procedures were compared on 15 criteria, treatment
      outcome of grade II and grade III hemorrhoids was decided chiefly on the basis of
      patient satisfaction index (subjective criterion) and ability of each procedure
      to deal with prolapse of internal hemorrhoidal masses (objective criterion):
      Findings in each case were recorded over a follow-up of four weeks (postoperative
      days 1, 3, 7, 15 and 30). Statistical analysis was done using Student's t test
      for parametric data and Chi square test & Mann-Whitney test for non-parametric
      data. P < 0.05 was considered significant. RBL had the advantages of being an OPD
      procedure requiring no anesthesia and was attended by significantly lesser
      postoperative recumbency (P < 0.001 ) and significantly lesser pain (P < 0.005 on
      day 1) as compared to KSL. However, Group II (KSL) scored better in terms of
      treatment outcome. In Group II, there was significantly high (P < 0.05) patient
      satisfaction index as compared to Group I. Group II reported 100% 'cure' (absence
      of hemorrhoidal masses even on proctoscopy) of internal hemorrhoidal prolapse as
      against 80% in Group I (RBL); however, this difference was statistically
      insignificant (P > 0.05). Both the groups were comparable statistically on all
      other grounds. Kshar Sutra Ligation is a useful form of treatment for Grades II
      and III internal hemorrhoids.

PMID- 20814520
TI  - Physicochemical characterization of Ayurvedic bhasma (Swarna makshika bhasma): An
      approach to standardization.
AB  - Swarna makshika [SM], a mineral having various therapeutic uses, has been used
      since long in Ayurveda. The present study was conducted to generate a fingerprint
      for raw and processed SM using techniques which can be used by pharmacies.
      Powdered SM was heated in an iron pan by adding lemon juice for 3 days, till
      liberation of sulfur fumes stopped. Bhasma of this shuddha SM was obtained by
      triturating it withit with shuddha gandhaka and lemon juice. It was then
      subjected to heat in 09* putas, and for firing in each puta, 4 kg cow dung cakes
      were used. To assure the quality of bhasma, rasa shastra quality control tests
      like nischandratva, varitara, amla pariksha, etc., were used. After the bhasma
      complied with these tests, the bhasma was analyzed using X-ray Diffraction (XRD)
      analysis of raw SM and SM bhasma revealed that raw SM contains CuFeS(2), and SM
      bhasma contains Fe(2)O(3), FeS(2), CuS and SiO(2). Scanning Electron Microscope
      (SEM) studies showed that the grains in SM bhasma were uniformly arranged in
      agglomerates of size 1-2 microns as compared to the raw SM which showed a
      scattered arrangement of grains of size 6-8 microns. It may be concluded that raw
      SM is a complex compound which gets converted into a mixture of simple compounds
      having very small particle size after the particular process of marana. This is
      the first report of fingerprinting of SM bhasma prepared using this particular
      method.

PMID- 20814521
TI  - Effect of hydroalcoholic extract of Sphaeranthus indicus against experimentally
      induced anxiety, depression and convulsions in rodents.
AB  - To investigate the effects of a hydroalcoholic extract of the Sphaeranthus
      indicus (SIE) against experimentally induced anxiety, depression and convulsions
      in rodents. The SIE (100, 200, 500 mg/kg, p.o.) was used in elevated plus maze,
      open field, forced swimming, and tail suspension tests in mice. The same doses
      were also used to evaluate its anticonvulsant effect on pentylenetetrazole (PTZ)
      induced convulsions in mice and maximal electroshock (MES)-induced convulsions in
      rats. SIE was found to increase the number of entries and the time spent in the
      open arms of the maze at a dose of 100 mg/kg, p.o., indicating its anxiolytic
      activity. On the other hand, higher doses of SIE (200 and 500 mg/kg, p.o.)
      decreased open arm entries and time spent in the open arms of the maze in the
      elevated plus maze test indicating an absence of anxiolytic activity. However,
      this effect could have been related to a decrease in the locomotor activity of
      the mice and not to an anxiogenic effect, as indicated by the reduction in the
      total number of entries in the elevated plus maze. SIE also (at doses of 200 and
      500 mg/kg, p.o.) decreased locomotor activity but did not affect emotional
      activity parameters in the open field test, suggesting a possible central nervous
      depressant activity. SIE also increased the immobility time in the forced
      swimming test at an oral dose of 500 mg/kg but did not significantly modify the
      activity in the tail suspension test. SIE protected rats against MES-induced
      convulsions and mice against PTZ-induced convulsions. Sphaeranthus indicus
      demonstrated anxiolytic, central nervous depressant, and anticonvulsant
      activities in rodents, thus supporting the folk medicinal use of this plant in
      nervous disorders.

PMID- 20814522
TI  - Effect of Triphala mouthwash on the caries status.
AB  - Nearly 60-70% of the child Indian population suffers from dental caries. Mouth
      rinsing is the most cost effective method of preventing dental caries. 'Triphala'
      has been a classic Ayurveda remedy, probably the best known among all Ayurvedic
      compounds. This study was conducted on 1501 students in the age group of 8-12
      years with the aim of determining the effect of Triphala mouthwash on prevention
      of dental caries (manifest caries) as well as incipient carious lesions, and also
      comparing the effect of Triphala and chlorhexidine mouthwashes. The incipient
      caries was recorded at 3, 6, 9 months intervals and manifest caries at 9 months
      interval. No significant increase in the DMFS scores was found at the end of 9
      months. Also, there was no significant increase in the incipient caries score
      towards the conclusion of the study. It was concluded that there was no
      significant difference between the Triphala and the chlorhexidine mouthwashes.

PMID- 20814523
TI  - Effect of the insulin plant (Costus igneus) leaves on dexamethasone-induced
      hyperglycemia.
AB  - Costus igneus, commonly known as insulin plant in India, belongs to the family
      Costaceae. Consumption of the leaves are believed to lower blood glucose levels,
      and diabetics who consumed the leaves of this plant did report a fall in their
      blood glucose levels. OBJECTIVES: The present study was planned to evaluate the
      effect of the leaves of Costus igeus on dexamethasone-induced hyperglycemia in
      male Wistar rats. Four groups of male Wistar rats (n= 6) were treated with 10
      mg/kg/day of dexamethasone subcutaneously for 20 days. From day 11 to day 20,
      different groups received 100, 250 or 500 mg/kg/day of powdered leaves of Costus
      igeus in distilled water orally or Glibenclamide 500 microg/kg orally. On the
      20th day, after overnight fasting, a retro-orbital puncture was performed for
      obtaining blood samples to estimate the fasting blood glucose level, and the same
      procedure was followed on the other eye 1 hour after a glucose load of 2.5 g/kg
      orally for estimation of post-glucose load blood glucose levels. Fasting blood
      sugar and postglucose load blood sugar levels were raised in the group that
      received dexamethasone when compared to normal controls (P < 0.001), whereas 250
      and 500 mg/kg powdered leaf of Costus igeus and Glibenclamide 500 microg/kg
      decreased the dexamethasone-induced hyperglycemia (P < 0.01). The leaves of
      Costus igeus reduced the fasting and postprandial blood sugar levels, bringing
      them towards normal, in dexamethasone-induced hyperglycemia in rats.

PMID- 20814524
TI  - Pharmacognostical studies of Hymenodictyon orixence (Roxb.) Mabb. leaf.
AB  - Hymenodictyon orixence is medicinally important plant found in India, Malaysia
      and Africa. Due to overexploitation the population of this species has decreased
      very rapidly. The present study includes pharmacognostical examination of this
      species. It includes morphological, anatomical, chemical and chromo
      fingerprinting characters of Hymenodictyon orixence leaf.

PMID- 20814525
TI  - A new glycosidic flavonoid from Jwarhar mahakashay (antipyretic) Ayurvedic
      preparation.
AB  - The aqueous extract of Jwarhar mahakashay Ayurvedic preparation (from the roots
      of Hemidesmus indicus R. Br., Rubia cordifolia L., Cissampelos pareira L.; fruits
      of Terminalia chebula Retz., Emblica officinalis Gaertn., Terminalia bellirica
      Roxb., Vitis vinifera L., Grewia asiatica L., Salvadora persica L. and granules
      of Saccharum officinarum L.) has been used as a traditional antipyretic.
      Experimental studies confirmed its antipyretic-analgesic effect with very low
      ulcerogenicity and toxicity. Flavonoids, glycosides and tannins were later found
      to be present in the extract. Detailed chemical investigations were undertaken
      after hydrolysis of extract using spectroscopic and chromatography methods to
      determine its active chemical constituent. UV-Visible spectroscopy showed
      absorbance maxima at 220 and 276 nm, while fourier transform infra-red
      investigations indicated an end carboxylic O-H structure at 2940 cm(-1)
      suggesting the presence of glycoside-linked flavonoids. Thin layer chromatography
      and high performance liquid chromatography also confirmed the possibility of at
      least one major and two minor compounds in this abstract. Detailed examination
      using gas chromatography-mass spectrometry led to the identification of the
      principal component as 2-(1-oxopropyl)-benzoic acid, which is quite similar to
      the active compound found in the standard drug Aspirin (2-acetyl-oxybenzoic
      acid).

PMID- 20814527
TI  - Management of pilonidal sinus by Kshar Sutra, a minimally invasive treatment.
AB  - A Pilonidal sinus (PNS) occurs in the cleavage between the buttocks (natal cleft)
      and can cause discomfort, embarrassment and absence from work. It is more common
      in men (as they have more hair) than in women. The most commonly used surgical
      techniques for this disorder include excision and primary closure and excision
      with reconstructive flap. However, the risk of recurrence or of developing an
      infection of the wound after the operation is high. Also, the patient requires
      longer hospitalization, and the procedure is expensive. There is a similarity
      between Shalyaj Nadi Vran described in Sushruta Samhita and Pilonidal sinus.
      Sushruta has advocated a minimally invasive para-surgical treatment, viz., Kshar
      Sutra procedure, for nadi vran. Hence this therapy was tried in Pilonidal sinus,
      and is described in this case report. Kshar Sutra treatment not only minimizes
      complications and recurrence but also enables the patient to resume work quicker
      and with less discomfort, impact upon body image and self-esteem as well as
      reduced cost.

PMID- 20814526
TI  - Tinospora cordifolia (Willd.) Hook. f. and Thoms. (Guduchi) - validation of the
      Ayurvedic pharmacology through experimental and clinical studies.
AB  - T. cordifolia (Guduchi) is a large, glabrous, perennial, deciduous, climbing
      shrub of weak and fleshy stem found throughout India. It is a widely used plant
      in folk and Ayurvedic systems of medicine. The chemical constituents reported
      from this shrub belong to different classes, such as alkaloids, diterpenoid
      lactones, glycosides, steroids, sesquiterpenoid, phenolics, aliphatic compounds
      and polysaccharides. Various properties of T. cordifolia, described in ancient
      texts of Ayurveda, like Rasayana, Sangrahi, Balya, Agnideepana, Tridoshshamaka,
      Dahnashaka, Mehnashaka, Kasa-swasahara, Pandunashaka, Kamla-Kushta
      Vataraktanashaka, Jwarhara, Krimihara, Prameha, Arshnashaka, Kricch
      Hridroganashak, etc., are acquiring scientific validity through modern research
      adopting "reverse pharmacological" approach. Potential medicinal properties
      reported by scientific research include anti-diabetic, antipyretic,
      antispasmodic, anti-inflammatory, anti-arthritic, antioxidant, anti-allergic,
      anti-stress, anti-leprotic, antimalarial, hepato-protective, immuno-modulatory
      and anti-neoplastic activities. This review brings together various properties
      and medicinal uses of T. cordifolia described in Ayurveda, along with
      phytochemical and pharmacological reports.

PMID- 20814528
TI  - Ayurveda education: A student's perspective.

PMID- 20814529
TI  - Study designs.

PMID- 20814530
TI  - Microbial content in Ayurvedic medicine.

PMID- 20814531
TI  - Sample size calculation.

PMID- 20814532
TI  - Author's reply.

PMID- 20814533
TI  - Global challenges of graduate level Ayurvedic education.

PMID- 20814534
TI  - Subacute thyroiditis following ginger (Zingiber officinale) consumption.

PMID- 20814535
TI  - Author's reply.

PMID- 20814536
TI  - A metabonomic approach to analyze the dexamethasone-induced cleft palate in mice.
AB  - Mice models are an important way to understand the relation between the fetus
      with cleft palate and changes of maternal biofluid. This paper aims to develop a
      metabonomics approach to analyze dexamethasone-induced cleft palate in pregnant
      C57BL/6J mice and to study the relationship between the change of endogenous
      small molecular metabolites in maternal plasma and the incidence of cleft palate.
      To do so, pregnant mice were randomly divided into two groups. The one group was
      injected with dexamethasone. On E17.5th day, the incident rates of cleft palate
      from embryos in two groups were calculated. The (1)H-NMR spectra from the
      metabolites in plasma in two groups was collected at same time. Then the data
      were analyzed using metabonomics methods (PCA and SIMCA). The results showed that
      the data from the two groups displayed distinctive characters, and the incidence
      of cleft palate were significantly different (P < .005). To conclude, this study
      demonstrates that the metabonomics approach is a powerful and effective method in
      detecting the abnormal metabolites from mother in the earlier period of embryos,
      and supports the idea that a change from dexamethasone induced in maternal
      metabolites plays an important role in the incidence of cleft palate.

PMID- 20814537
TI  - Metabolomics reveals relationship between plasma inositols and birth weight:
      possible markers for fetal programming of type 2 diabetes.
AB  - Epidemiological studies in man and with experimental animal models have shown
      that intrauterine growth restriction (IUGR) resulting in low birth weight is
      associated with higher risk of programming welfare diseases in later life. In the
      pig, severe IUGR occurs naturally and contribute substantially to a large
      intralitter variation in birth weight and may therefore be a good model for man.
      In the present paper the natural form of IUGR in pigs was studied close to term
      by nuclear magnetic resonance (NMR-)based metabolomics. The NMR-based
      investigations revealed different metabolic profiles of plasma samples from low
      birth weight (LW) and high-birth weight (HW) piglets, respectively, and
      differences were assigned to levels of glucose and myo-inositol. Further studies
      by GC-MS revealed that LW piglets had a significant higher concentration of
      myoinositol and D-chiro-inositol in plasma compared to larger littermates. Myo
      inositol and D-chiro-inositol have been coupled with glucose intolerance and
      insulin resistance in adults, and the present paper therefore suggests that IUGR
      is related to impaired glucose metabolism during fetal development, which may
      cause type 2 diabetes in adulthood.

PMID- 20814538
TI  - Vascular Complications of Systemic Sclerosis during Pregnancy.
AB  - Systemic sclerosis (SSc) is a chronic autoimmune disorder characterized by
      progressive fibrosis of the skin and visceral tissues as well as a
      noninflammatory vasculopathy. Vascular disease in systemic sclerosis is a major
      cause of morbidity and mortality among nonpregnant patients with SSc and is even
      a bigger concern in the pregnant SSc patient, as the underlying vasculopathy may
      prevent the required hemodynamic changes necessary to support a growing
      pregnancy. Vascular manifestations including scleroderma renal crisis and
      pulmonary arterial hypertension should be considered relative contraindications
      against pregnancy due to the high associations of both maternal and fetal
      morbidity and mortality. In contrast, Raynaud's phenomenon may actually improve
      somewhat during pregnancy. Women with SSc who are considering a pregnancy or
      discover they are pregnant require evaluation for the presence and extent of
      underlying vasculopathy. In the absence of significant visceral vasculopathy,
      most women with SSc can expect to have reasonable pregnancy outcomes.

PMID- 20814539
TI  - Adaptive radiation for lung cancer.
AB  - The challenges of lung cancer radiotherapy are intra/inter-fraction tumor/organ
      anatomy/motion changes and the need to spare surrounding critical structures.
      Evolving radiotherapy technologies, such as four-dimensional (4D) image-based
      motion management, daily on-board imaging and adaptive radiotherapy based on
      volumetric images over the course of radiotherapy, have enabled us to deliver
      higher dose to target while minimizing normal tissue toxicities. The image-guided
      radiotherapy adapted to changes of motion and anatomy has made the radiotherapy
      more precise and allowed ablative dose delivered to the target using novel
      treatment approaches such as intensity-modulated radiation therapy, stereotactic
      body radiation therapy, and proton therapy in lung cancer, techniques used to be
      considered very sensitive to motion change. Future clinical trials using real
      time tracking and biological adaptive radiotherapy based on functional images are
      proposed.

PMID- 20814540
TI  - Adnexal Torsion during Pregnancy after Oocyte In Vitro Maturation and
      Intracytoplasmic Sperm Injection Cycle.
AB  - We report a case of right adnexal torsion during pregnancy after an oocyte in
      vitro maturation and intracitoplasmic sperm injection cycle in patient with
      polycystic ovary syndrome. A 31-year-old woman with a typical clinical disorder
      of polycystic ovarian syndrome was included in an oocyte in vitro maturation
      program. Right adnexal torsion occurred two days after embryo transfer, and
      laparoscopy detorsion was successfully performed with preservation of adnexa. The
      patient had a full-term pregnancy and delivered a healthy infant at 40 weeks of
      gestation. To our knowledge this is the first report of adnexal torsion after an
      oocyte in vitro maturation and intracitoplasmic sperm injection program.

PMID- 20814541
TI  - Short-term exercise approaches on menopausal symptoms, psychological health, and
      quality of life in postmenopausal women.
AB  - Objective. This study was designed to determine the effects of different short
      term exercise programs on menopausal symptoms, psychological health, and quality
      of life in postmenopausal women. Material and Methods. Forty-two women were
      chosen from volunteering postmenopausal women presenting to the Department of
      Obstetrics and Gynecology of Bayindir Hospital between March and December 2009.
      The women aged 45-60 years and experiencing menopause naturally were included in
      the study. They were randomly divided into aerobic (n = 18) and resistance (n =
      18) exercise groups. The women exercised 3 days per week for 8 weeks under the
      supervision of a physiotherapist. Aerobic exercise training was performed through
      a bicycle ergometer. Before and after the training, lipid profiles were measured
      and menopausal symptoms, psychological health, depression, and the quality of
      life were assessed through questionnaires. Results. In both exercise groups, no
      significant changes in lipid profiles were observed. In the resistance exercise
      group, excluding the urogenital complaints, there were significant improvements
      in all subscales of Menopausal Rating Scale (MRS). In the resistance exercise
      group, excluding the phobic anxiety, there were significant improvements in all
      subscales of The Symptom Checklist. Depression levels significantly decreased in
      both groups. Improvements were observed in all subscales of menopause-specific
      quality of life questionnaire in both groups except for sexual symptoms.
      Conclusion. Resistance exercise and aerobic exercise were found to have a
      positive impact on menopausal symptoms, psychological health, depression, and
      quality of life.

PMID- 20814543
TI  - Epidemiological investigation of bovine ephemeral Fever outbreaks in Israel.
AB  - Outbreaks of bovine ephemeral fever (BEF) occurred in Israel in 1990, 1999, and
      2004. The main patterns of BEF spread were similar in the 1990 and in 1999
      epidemics, and the BEF virus was probably carried in vectors transported by air
      streams across the Rift Valley and the Red Sea. In the 2004 outbreak, the primary
      focus of the disease was the southern Mediterranean coastal plain and the disease
      agent was apparently brought by infected mosquitoes carried from their breeding
      site in the Nile Delta by the south-western winds. The disease broke out under
      optimal ecological conditions, among a vulnerable cattle population and spread
      rapidly; it showed essentially a spring-summer herd incidence and terminated soon
      after the night average ambient temperature fell below 16 degrees C in late
      autumn. The herd incidence of the disease reached 78.4%, 97.7%, and 100% in 1990,
      1999, and 2004, respectively. The highest herd incidence, morbidity, and case
      fatality rates were noted in dairy cattle herds in the Jordan Valley, with
      morbidity of 20%, 38.6%, and 22.2%, and case fatality rate among affected animals
      of 2%, 8.6%, and 5.4% in 1990, 1999, and 2004, respectively. The average sero
      positivity to BEF in 1999 was 39.5%, which matched the morbidity rate. Comparison
      among the various age groups showed that the lowest morbidity rates were observed
      in the youngest age group, that is, heifers up to 1 year, with 3.2%, 3.6%, and
      4.2% in 1990, 1999, and 2004, respectively. In heifers from 1 year to calving,
      the morbidity rates were 13.8%, 14.9%, and 28%, respectively, in first calvers
      30.8%, 31.6%, and 28.3%, respectively, and in cows 34.3%, 35.7%, and 27.2%,
      respectively. All affected cattle were over the age of 3 months. It is
      hypothesized that mosquitoes and not Culicoides spp. are the vectors of the BEF
      virus in Israel.

PMID- 20814542
TI  - Therapeutic Implications of PPARgamma in Cardiovascular Diseases.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) is the members of
      the nuclear receptor superfamily as a master transcriptional factor that promotes
      differentiation of preadipocytes by activating adipose-specific gene expression.
      Although PPARgamma is expressed predominantly in adipose tissue and associated
      with adipocyte differentiation and glucose homeostasis, PPARgamma is also present
      in a variety of cell types including vascular cells and cardiomyocytes.
      Activation of PPARgamma suppresses production of inflammatory cytokines, and
      there is accumulating data that PPARgamma ligands exert antihypertrophy of
      cardiomyocytes and anti-inflammatory, antioxidative, and antiproliferative
      effects on vascular wall cells and cardiomyocytes. In addition, activation of
      PPARgamma is implicated in the regulation of endothelial function, proliferation
      and migration of vascular smooth muscle cells, and activation of macrophages.
      Many studies suggest that PPARgamma ligands not only ameliorate insulin
      sensitivity, but also have pleiotropic effects on the pathophysiology of
      atherosclerosis, cardiac hypertrophy, ischemic heart, and myocarditis.

PMID- 20814544
TI  - G-quadruplex nucleic acids.

PMID- 20814547
TI  - Pathology of macular foveoschisis associated with degenerative myopia.
AB  - This is a clinicopathological paper on the histologic findings in myopia
      associated macular foveoschisis. The findings on ophthalmic pathological study of
      a 73-year-old woman with high myopia are reviewed. Multiple retinoschisis
      cavities involving both the macula and retinal periphery were disclosed. Our
      paper offers tissue evidence and supports recent ocular coherence tomography
      reports of eyes with high myopia and associated macular foveoschisis.

PMID- 20814545
TI  - TLR4 and Insulin Resistance.
AB  - Chronic inflammation is a key feature of insulin resistance and obesity. Toll
      Like Receptor 4 (TLR4), involved in modulating innate immunity, is an important
      mediator of insulin resistance and its comorbidities. TLR4 contributes to the
      development of insulin resistance and inflammation through its activation by
      elevated exogenous ligands (e.g., dietary fatty acids and enteric
      lipopolysaccharide) and endogenous ligands (e.g., free fatty acids) which are
      elevated in obese states. TLR4, expressed in insulin target tissues, activates
      proinflammatory kinases JNK, IKK, and p38 that impair insulin signal transduction
      directly through inhibitory phosphorylation of insulin receptor substrate (IRS)
      on serine residues. TLR4 activation also leads to increased transcription of pro
      inflammatory genes, resulting in elevation of cytokine, chemokine, reactive
      oxygen species, and eicosanoid levels that promote further insulin
      desensitization within the target cell itself and in other cells via paracrine
      and systemic effects. Increased understanding of cell type-specific TLR4-mediated
      effects on insulin action present the opportunity and challenge of developing
      related therapeutic approaches for improving insulin sensitivity while preserving
      innate immunity.

PMID- 20814546
TI  - Tumor microenvironment and immune effects of antineoplastic therapy in
      lymphoproliferative syndromes.
AB  - Lymphomas represent a wide group of heterogenic diseases with different
      biological and clinical behavior. The underlying microenvironment-specific
      composition seems to play an essential role in this scenario, harboring the
      ability to develop successful immune responses or, on the contrary, leading to
      immune evasion and even promotion of tumor growth. Depending on surrounding
      lymphoid infiltrates, lymphomas may have different prognosis. Moreover, recent
      evidences have emerged that confer a significant impact of main lymphoma's
      treatment over microenvironment, with clinical consequences. In this review, we
      summarize these concepts from a pathological and clinical perspective. Also, the
      state of the art of lymphoma's anti-idiotype vaccine development is revised,
      highlighting the situations where this strategy has proven to be successful and
      eventual clues to obtain better results in the future.

PMID- 20814548
TI  - Insulin-induced electrophysiology changes in human pleura are mediated via its
      receptor.
AB  - BACKGROUND: Insulin directly changes the sheep pleural electrophysiology. The aim
      of this study was to investigate whether insulin induces similar effects in human
      pleura, to clarify insulin receptor's involvement, and to demonstrate if
      glibenclamide (hypoglycemic agent) reverses this effect. METHODS: Human parietal
      pleural specimens were mounted in Ussing chambers. Solutions containing insulin
      or glibenclamide and insulin with anti-insulin antibody, anti-insulin receptor
      antibody, and glibenclamide were used. The transmesothelial resistance (R(TM))
      was determined. Immunohistochemistry for the presence of Insulin Receptors (IRa,
      IRb) was also performed. RESULTS: Insulin increased R(TM) within 1st min (P =
      .016), when added mesothelially which was inhibited by the anti-insulin and anti
      insulin receptor antibodies. Glibenclamide also eliminated the insulin-induced
      changes. Immunohistochemistry verified the presence of IRa and IRb. CONCLUSION:
      Insulin induces electrochemical changes in humans as in sheep via interaction
      with its receptor. This effect is abolished by glibenclamide.

PMID- 20814549
TI  - Ileocecal adenocarcinoma and ureteral transitional cell carcinoma with multiple
      sebaceous tumors and keratoacanthomas in a case of muir-torre syndrome.
AB  - Cutaneous neoplasms including sebaceous tumors, keratoacanthomas, and basal cell
      carcinomas with sebaceous differentiation can be markers of internal malignancy
      associated with the Muir-Torre Syndrome (MTS). We report a 56-year-old man with a
      diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) and ureteral
      transitional cell carcinoma who subsequently developed two sebaceous gland
      neoplasms and several keratoacanthomas, leading to the diagnosis of MTS. Our case
      highlights the clinical advantages of immunohistochemistry (IHC) in identifying
      mutations in the mismatch repair (MMR) genes responsible for both HNPCC and MTS.
      The importance of continued clinical suspicion in the dermatological assessment
      of patients with sebaceous neoplasms is emphasized.

PMID- 20814550
TI  - Anesthesia for pediatric deep brain stimulation.
AB  - In patients refractory to medical therapy, deep brain stimulations (DBSs) have
      emerged as the treatment of movement disorders particularly Parkinson's disease.
      Their use has also been extended in pediatric and adult patients to treat
      epileptogenic foci. We here performed a retrospective chart review of anesthesia
      records from 28 pediatric cases of patients who underwent DBS implantation for
      dystonia using combinations of dexmedetomidine and propofol-based anesthesia.
      Complications with anesthetic techniques including airway and cardiovascular
      difficulties were analyzed.

PMID- 20814551
TI  - A case of supplement-induced hepatotoxicity.
AB  - A 45-year-old Caucasian male presented with a two-week history of jaundice and
      right-upper quadrant (RUQ) abdominal pain. Transaminases and biliary enzymes were
      markedly elevated with hyperferritinemia and mildly elevated INR. Imaging tests
      showed no significant abnormality. He denied prescription or over-the-counter
      (OTC) medication use, but he had been taking at least 9 dietary supplements for
      12 months. Other causes of liver disease were excluded. His supplements were
      discontinued, and his liver-associated enzymes significantly markedly improved
      over the next 6 weeks and remained normal after one year suggesting supplement
      induced hepatotoxicity. Due to the number of supplements, no specific agent could
      be identified as the primary cause of his liver injury. This case illustrates the
      importance of inquiring and educating patients of the potential harmful risks of
      over-the-counter medications and supplements.

PMID- 20814552
TI  - The vascular microenvironment and systemic sclerosis.
AB  - The role of the vascular microenvironment in the pathogenesis Systemic Sclerosis
      (SSc) is appreciated clinically as Raynaud's syndrome with capillary nail bed
      change. This manifestation of vasculopathy is used diagnostically in both limited
      and diffuse cutaneous subsets of SSc, and is thought to precede fibrosis. The
      degree of subsequent fibrosis may also be determined by the vascular
      microenvironment. This paper describes why the vascular microenvironment might
      determine the degree of end-organ damage that occurs in SSc, with a focus on
      vascular cell senescence, endothelial progenitor cells (EPC) including
      multipotential mesenchymal stem cells (MSC), pericytes, and angiogenic monocytes.
      An explanation of the role of EPC, pericytes, and angiogenic monocytes is
      important to an understanding of SSc pathogenesis. An evolving understanding of
      the vascular microenvironment in SSc may allow directed treatment.

PMID- 20814554
TI  - Successful magnetic resonance imaging-guided focused ultrasound surgery for
      recurrent uterine fibroid previously treated with uterine artery embolization.
AB  - A 45-year-old premenopausal woman was referred to our clinic due to recurring
      symptoms of uterine fibroids, nine years after a uterine artery embolization
      (UAE). At the time of screening, the patient presented with bilateral impairment
      and narrowing of the uterine arteries, which increased the risk of arterial
      perforation during repeated UAE procedures. The patient was subsequently referred
      for magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS)
      treatment. Following the treatment, the patient experienced a significant
      improvement in symptoms (symptom severity score was reduced from 47 to 12 by 1
      year post-treatment). MR images at 3 months showed a 49% decrease in fibroid
      volume. There were no adverse events during the treatment or the follow-up
      period. This case suggests that MRgFUS can be an effective treatment option for
      patients with recurrent fibroids following previous UAE treatment.

PMID- 20814553
TI  - Rat strain differences in susceptibility to alcohol-induced chronic liver injury
      and hepatic insulin resistance.
AB  - The finding of more severe steatohepatitis in alcohol fed Long Evans (LE)
      compared with Sprague Dawley (SD) and Fisher 344 (FS) rats prompted us to
      determine whether host factors related to alcohol metabolism, inflammation, and
      insulin/IGF signaling predict proneness to alcohol-mediated liver injury. Adult
      FS, SD, and LE rats were fed liquid diets containing 0% or 37% (calories) ethanol
      for 8 weeks. Among controls, LE rats had significantly higher ALT and reduced
      GAPDH relative to SD and FS rats. Among ethanol-fed rats, despite similar blood
      alcohol levels, LE rats had more pronounced steatohepatitis and fibrosis, higher
      levels of ALT, DNA damage, pro-inflammatory cytokines, ADH, ALDH, catalase, GFAP,
      desmin, and collagen expression, and reduced insulin receptor binding relative to
      FS rats. Ethanol-exposed SD rats had intermediate degrees of steatohepatitis,
      increased ALT, ADH and profibrogenesis gene expression, and suppressed insulin
      receptor binding and GAPDH expression, while pro-inflammatory cytokines were
      similarly increased as in LE rats. Ethanol feeding in FS rats only reduced IL-6,
      ALDH1-3, CYP2E1, and GAPDH expression in liver. In conclusion, susceptibility to
      chronic steatohepatitis may be driven by factors related to efficiency of ethanol
      metabolism and degree to which ethanol exposure causes hepatic insulin resistance
      and cytokine activation.

PMID- 20814555
TI  - An abdominal presentation of churg-strauss syndrome.
AB  - Churg-Strauss syndrome is a small and medium vessel vasculitis that is also known
      as allergic granulomatous angiitis. It most commonly presents with an asthma like
      symptoms. It was first described in Mount Siani Hospital, New York in 1951 by
      Jacob Churg and Lotte Stauss and was recognised after the study of a series of 13
      patients who had asthma, eosinophilia, granulomatous inflammation necrotising
      systemic vasculitis and necrotising glomerulonephritis. We describe a case of
      Churg-Strauss syndrome presenting with abdominal pain and later during the
      hospital admission a mono-neuritis multiplex syndrome affecting the lower limbs.
      The patient presented in such an atypical fashion with abdominal signs and
      symptoms that they required laparotomy and the diagnosis was made after
      histological examination of tissue taken at the time of surgery. Treatment with
      immunosuppression and aggressive rehabilitation achieved a progressive recovery
      which continued on discharge from hospital.

PMID- 20814556
TI  - Rapid-Onset Acute Respiratory Distress Syndrome (ARDS) in a Patient Undergoing
      Metastatic Liver Resection: A Case Report and Review of the Literature.
AB  - Metastatic liver resection following cytoreductive chemotherapy is an accepted
      treatment for oligometastatic tumor diseases. Although pulmonary complications
      are frequently reported in patients undergoing liver surgery including liver
      transplantation, life-threatening acute respiratory failures in the absence of
      aspiration, embolism, transfusion-related acute lung injury (TRALI), pulmonary
      infection, or an obvious source of systemic sepsis are rare. We performed an
      extensive clinical review of a patient undergoing metastatic liver resection who
      had a clinical course compatible to an acute respiratory distress syndrome (ARDS)
      without an obvious cause except for the surgical procedure and multiple
      preoperative chemotherapies. We hypothesize that either the surgical procedure
      mediated by cytokines and tumor necrosis factor or possible toxic effects of
      oxygen applied during general anesthesia were associated with life-threatening
      respiratory failure in the patient. Discrete and subclinical inflammated alveoli
      (probably due to multiple preoperative chemotherapies with substances at
      potential risk for interstitial pneumonitis as well as chest radiation) might
      therefore be considered as risk factors.

PMID- 20814557
TI  - The Prognostic Impact of Protein Expression of E-Cadherin-Catenin Complexes
      Differs between Rectal and Colon Carcinoma.
AB  - The E-cadherin-catenin complex provides cell-cell adhesion. In order for a
      carcinoma to metastasize, cancer cells must let go of their hold of neighboring
      cells in the primary tumor. The presence of components of the E-cadherin-catenin
      complex in 246 rectal adenocarcinomas was examined by immunohistochemistry and
      compared to their presence in 219 colon carcinomas. The expression data were
      correlated to clinical information from the patients' records. There were
      statistically significant differences in protein expression between the rectal
      and the colon carcinomas regarding membranous beta-catenin, gamma-catenin, p120
      catenin, and E-cadherin, as well as nuclear beta-catenin. In the rectal
      carcinomas, there was a significant inverse association between the expression of
      p120-catenin in cell membranes of the primary tumors and the occurrence of local
      recurrence, while membranous protein expression of beta-catenin was inversely
      related to distant metastases.

PMID- 20814558
TI  - Pancreatic anastomosis disruption seven years postpancreaticoduodenectomy.
AB  - We are reporting a case of a 22 year-old female patient, who underwent a
      pancreaticoduodenectomy previously for a solid-pseudopapillary neoplasm of the
      pancreas and was re-admitted seven years later with a pancreatic leak following
      disruption of the pancreatico-jejunal anastomosis. Exploratory laparotomy
      revealed a large collection at the level of the pancreatic anastomosis with major
      disruption of the pancreatico-jejunal anastomosis. The pancreatic stump was
      refreshed as well as the jejunal site and a duct to mucosa anastomosis was
      performed. She remains well with a follow up of 18 months.

PMID- 20814559
TI  - Levosimendan as treatment option in severe verapamil intoxication: a case report
      and review of the literature.
AB  - Cardiovascular shock due to verapamil intoxication is often refractory to
      standard resuscitation methods. Recommended therapy includes prevention of
      further absorption of the drug, inotropic therapy, calcium gluconate, and
      hyperinsulinemia/euglycemia therapy. Often further measures are needed such as
      ventricular pacing or mechanical circulatory support. Still, mortality remains
      high. Levosimendan, an inotropic agent, that enhances myofilament response to
      calcium, increases myocardial contraction and could therefore be beneficial in
      verapamil intoxication. Here, we report the case of a 60-year-old patient with
      clinically severe verapamil poisoning who presented with shock, bradycardia, and
      sopor. Standard therapy including high-dose inotropes failed to ameliorate the
      signs of intoxication. But additional therapy with levosimendan led to rapid
      improvement. Based on this observation, the literature is reviewed focusing on
      utilization of levosimendan in the treatment of calcium channel blocker overdose.
      We suggest to consider levosimendan as additional treatment option in patients
      with cardiovascular shock due to verapamil intoxication that are refractory to
      standard management.

PMID- 20814560
TI  - Incidental detection of internal jugular vein thrombosis secondary to undiagnosed
      benign substernal goiter.
AB  - Internal jugular vein thrombosis is a serious event with potentially fatal
      outcome, where the clinical symptoms may be vague or absent. This paper refers to
      a rare case where routine carotid Doppler ultrasound prior to coronary artery
      bypass grafting (CABG) and aortic valve replacement (AVR) in a 76-year-old man,
      incidentally revealed thrombosis of the right internal jugular vein. Thoracic CT
      demonstrated an underlying, large, benign substernal multinodular goiter, mainly
      involving the right lobe, causing compression and displacement of the great
      vessels. A successful, one-stage operation including ligation of the internal
      jugular vein to avoid pulmonary embolism and hemithyroidectomy, combined with the
      scheduled CABG and AVR, was performed. This case illustrates that benign
      substernal goiter may be associated with asymptomatic internal jugular vein
      thrombosis. Carotid Doppler ultrasound should involve evaluation of the internal
      jugular vein concerning thrombosis as its presence may reveal space-occupying
      lesions in the thorax.

PMID- 20814561
TI  - Femoral hernia with a twist.

PMID- 20814562
TI  - The Khmer 'Weak Heart' Syndrome: Fear of Death from Palpitations.
AB  - According to the Khmer conception, a person suffering 'weak heart' (khsaoy beh
      daung) has episodes of palpitations on slight provocation (e.g. triggered by
      orthostasis, anger, a noise, worry, an odor or exercise) and runs the risk of
      dying of heart arrest during these periods of palpitations; too, the sufferer
      typically has other symptoms attributed to the purported cardiac dysfunction:
      fatigue, shortness of breath, and orthostatic dizziness. Many Khmer refugees
      suffer this cultural syndrome, an anxious-dysphoria ontology, most probably of
      French colonial provenance. The syndrome demonstrates considerable overlap with
      those Western illness categories that feature panic attacks, in particular post
      traumatic stress disorder (PTSD) and panic disorder. In a psychiatric clinic
      survey, 60 percent (60/100) of those assessed believed themselves to currently
      suffer 'weak heart'; 90 percent (54/60) of those considering themselves to suffer
      from 'weak heart' thought that palpitations (e.g., those resulting from a loud
      noise or orthostasis) might result in death. The article illustrates the
      profoundly culturally constructed nature of 'cardiac sensations,' located in a
      specific historical trajectory and episteme; too, the article suggests that
      trauma may result more in panic disorder than 'PTSD' when autonomic arousal
      symptoms (in the present case, palpitations) are considered potentially life
      threatening.

PMID- 20814563
TI  - Small Bowel Obstruction due to Mesodiverticular Band of Meckel's Diverticulum: A
      Case Report.
AB  - Meckel's diverticulum is the most common congenital anomaly of the small
      intestine. Common complications related to a Meckel's diverticulum include
      haemorrhage, intestinal obstruction, and inflammation. Small bowel obstruction
      due to mesodiverticular band of Meckel's diverticulum is a rare complication.
      Herein, we report the diagnosis and management of a small bowel obstruction
      occurring due to mesodiverticular band of a Meckel's diverticulum.

PMID- 20814564
TI  - Kikuchi-fujimoto disease associated with myasthenia gravis: a case report.
AB  - Kikuchi-Fujimoto disease is a self-limited benign condition of unknown etiology
      characterized by cervical lymphadenopathy, fever, and leucopenia. An autoimmune
      hypothesis has been suggested and an association with systemic lupus
      erythematosus, Sjogren's disease, and antiphospholipid syndrome has been noted.
      We report a 27-year-old male who presented for evaluation of weakness and he was
      diagnosed with seropositive generalized myasthenia gravis and underwent a
      thymectomy. He was stable until five months post-thymectomy, when he developed a
      high fever associated with nontender cervical lymphadenopathy, chills, and night
      sweats. Histopathology of a cervical lymph gland biopsy was compatible with
      Kikuchi-Fujimoto lymphadenitis. He improved spontaneously and was asymptomatic at
      the followup six months later. Our case expands the association of Kikuchi
      Fujimoto disease with autoimmune disorders to include myasthenia gravis.

PMID- 20814566
TI  - THE EFFECT OF BEREAVEMENT DUE TO SUICIDE ON SURVIVORS' DEPRESSION: A STUDY OF
      CHINESE SAMPLES.
AB  - The affective effect of suicide on people around is assessed with the Center for
      Epidemiologic Studies Depression Scale (CES-D), and some correlates are examined
      to identify characteristics of the bereaved individuals who score high on
      depression. We used the informants of 66 suicides as subjects for study and the
      informants of 66 living people as the control group. For each suicide and living
      person, we interviewed two informants: one family member and one friend. Data
      collection was accomplished in China in the summer of 2003. Results indicate that
      the bereaved people (informants of the suicides) are more likely to experience
      depression than those people in the control group. The closer the relationship to
      the suicide, the higher the degree of depression. While the survivor's education
      and income are negatively correlated with his or her depression level, neither
      age nor gender is a predictor of depression in the sample. Given the strong
      relationship between suicide and depression, the bereaved survivors of suicide
      could be a high risk group of suicide. Further and larger study is warranted to
      investigate more details of the high risk group so as to recommend prevention
      measures.

PMID- 20814565
TI  - Neural signatures of intransitive preferences.
AB  - It is often assumed that decisions are made by rank-ordering and thus comparing
      the available choice options based on their subjective values. Rank-ordering
      requires that the alternatives' subjective values are mentally represented at
      least on an ordinal scale. Because one alternative cannot be at the same time
      better and worse than another alternative, choices should satisfy transitivity
      (if alternative A is preferred over B, and B is preferred over C, A should be
      preferred over C). Yet, individuals often demonstrate striking violations of
      transitivity (preferring C over A). We used functional magnetic resonance imaging
      to study the neural correlates of intransitive choices between gambles varying in
      magnitude and probability of financial gains. Behavioral intransitivities were
      common. They occurred because participants did not evaluate the gambles
      independently, but in comparison with the alternative gamble presented. Neural
      value signals in prefrontal and parietal cortex were not ordinal-scaled and
      transitive, but reflected fluctuations in the gambles' local, pairing-dependent
      preference-ranks. Detailed behavioral analysis of gamble preferences showed that,
      depending on the difference in the offered gambles' attributes, participants gave
      variable priority to magnitude or probability and thus shifted between preferring
      richer or safer gambles. The variable, context-dependent priority given to
      magnitude and probability was tracked by insula (magnitude) and posterior
      cingulate (probability). Their activation-balance may reflect the individual
      decision rules leading to intransitivities. Thus, the phenomenon of
      intransitivity is reflected in the organization of the neural systems involved in
      risky decision-making.

PMID- 20814567
TI  - Isolated abdominal wall actinomycosis associated with an intrauterine
      contraceptive device: a case report and review of the relevant literature.
AB  - Isolated abdominal wall actinomycosis in the presence of an intrauterine
      contraceptive device (IUCD) is extremely rare and only six such cases have been
      reported in the literature. We report a case where clinical and radiological
      examinations revealed a pseudotumor within the anterior abdominal wall. After
      being lost to follow-up, the patient presented two years later with the
      enlargement of the mass. The mass including the affected anterior abdominal wall
      was completely excised. The diagnosis of actinomycosis was established
      postoperatively by histopathological examination. Further questioning concerning
      her gynecological history revealed long-term use of the same IUCD. Surgical
      excision of the actinomycotic pseudotumour and removal of the IUCD followed by
      antibiotic therapy resulted in the full recovery of the patient.

PMID- 20814568
TI  - DIFFEOMORPHIC ACTIVE CONTOURS.
AB  - In this study we present a geometric flow approach to the segmentation of three
      dimensional medical images obtained from magnetic resonance imaging (MRI) or
      computed tomography (CT) scan methods, by minimizing a cost function. This energy
      term is based on the intensity of the original image and its minimum is found
      following a gradient descent curve in an infinite-dimensional space of
      diffeomorphisms (Diff) to preserve topology. The general framework is reminiscent
      of variational shape optimization methods, but remains closer to general
      developments on deformable template theory of geometric flows. In our case, the
      metric that provides the gradient is defined as a right invariant inner product
      on the tangent space (??) at the identity of the group of diffeomorphisms,
      following the general Lie group approach suggested by Arnold [2]. To avoid local
      solutions of the optimization problem and to mitigate the influence of several
      sources of noise, a finite set of control points is defined on the boundary of
      the template binary images, yielding a projected gradient descent on Diff.

PMID- 20814569
TI  - TNF inhibits Notch-1 in skeletal muscle cells by Ezh2 and DNA methylation
      mediated repression: implications in duchenne muscular dystrophy.
AB  - BACKGROUND: Classical NF-kappaB signaling functions as a negative regulator of
      skeletal myogenesis through potentially multiple mechanisms. The inhibitory
      actions of TNFalpha on skeletal muscle differentiation are mediated in part
      through sustained NF-kappaB activity. In dystrophic muscles, NF-kappaB activity
      is compartmentalized to myofibers to inhibit regeneration by limiting the number
      of myogenic progenitor cells. This regulation coincides with elevated levels of
      muscle derived TNFalpha that is also under IKKbeta and NF-kappaB control.
      METHODOLOGY/PRINCIPAL FINDINGS: Based on these findings we speculated that in
      DMD, TNFalpha secreted from myotubes inhibits regeneration by directly acting on
      satellite cells. Analysis of several satellite cell regulators revealed that
      TNFalpha is capable of inhibiting Notch-1 in satellite cells and C2C12 myoblasts,
      which was also found to be dependent on NF-kappaB. Notch-1 inhibition occurred at
      the mRNA level suggesting a transcriptional repression mechanism. Unlike its
      classical mode of action, TNFalpha stimulated the recruitment of Ezh2 and Dnmt-3b
      to coordinate histone and DNA methylation, respectively. Dnmt-3b recruitment was
      dependent on Ezh2. CONCLUSIONS/SIGNIFICANCE: We propose that in dystrophic
      muscles, elevated levels of TNFalpha and NF-kappaB inhibit the regenerative
      potential of satellite cells via epigenetic silencing of the Notch-1 gene.

PMID- 20814570
TI  - Prioritizing land and sea conservation investments to protect coral reefs.
AB  - BACKGROUND: Coral reefs have exceptional biodiversity, support the livelihoods of
      millions of people, and are threatened by multiple human activities on land (e.g.
      farming) and in the sea (e.g. overfishing). Most conservation efforts occur at
      local scales and, when effective, can increase the resilience of coral reefs to
      global threats such as climate change (e.g. warming water and ocean
      acidification). Limited resources for conservation require that we efficiently
      prioritize where and how to best sustain coral reef ecosystems.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we develop the first prioritization approach
      that can guide regional-scale conservation investments in land- and sea-based
      conservation actions that cost-effectively mitigate threats to coral reefs, and
      apply it to the Coral Triangle, an area of significant global attention and
      funding. Using information on threats to marine ecosystems, effectiveness of
      management actions at abating threats, and the management and opportunity costs
      of actions, we calculate the rate of return on investment in two conservation
      actions in sixteen ecoregions. We discover that marine conservation almost always
      trumps terrestrial conservation within any ecoregion, but terrestrial
      conservation in one ecoregion can be a better investment than marine conservation
      in another. We show how these results could be used to allocate a limited budget
      for conservation and compare them to priorities based on individual criteria.
      CONCLUSIONS/SIGNIFICANCE: Previous prioritization approaches do not consider both
      land and sea-based threats or the socioeconomic costs of conserving coral reefs.
      A simple and transparent approach like ours is essential to support effective
      coral reef conservation decisions in a large and diverse region like the Coral
      Triangle, but can be applied at any scale and to other marine ecosystems.

PMID- 20814571
TI  - Role of JNK in a Trp53-dependent mouse model of breast cancer.
AB  - The cJun NH2-terminal kinase (JNK) signal transduction pathway has been
      implicated in mammary carcinogenesis. To test the role of JNK, we examined the
      effect of ablation of the Jnk1 and Jnk2 genes in a Trp53-dependent model of
      breast cancer using BALB/c mice. We detected no defects in mammary gland
      development in virgin mice or during lactation and involution in control studies
      of Jnk1(-/-) and Jnk2(-/-) mice. In a Trp53(-/+) genetic background, mammary
      carcinomas were detected in 43% of control mice, 70% of Jnk1(-/-) mice, and 53%
      of Jnk2(-/-) mice. These data indicate that JNK1 and JNK2 are not essential for
      mammary carcinoma development in the Trp53(-/+) BALB/c model of breast cancer. In
      contrast, this analysis suggests that JNK may partially contribute to tumor
      suppression. This conclusion is consistent with the finding that tumor-free
      survival of JNK-deficient Trp53(-/+) mice was significantly reduced compared with
      control Trp53(-/+) mice. We conclude that JNK1 and JNK2 can act as suppressors of
      mammary tumor development.

PMID- 20814572
TI  - APPL proteins FRET at the BAR: direct observation of APPL1 and APPL2 BAR domain
      mediated interactions on cell membranes using FRET microscopy.
AB  - BACKGROUND: Human APPL1 and APPL2 are homologous RAB5 effectors whose binding
      partners include a diverse set of transmembrane receptors, signaling proteins,
      and phosphoinositides. APPL proteins associate dynamically with endosomal
      membranes and are proposed to function in endosome-mediated signaling pathways
      linking the cell surface to the cell nucleus. APPL proteins contain an N-terminal
      Bin/Amphiphysin/Rvs (BAR) domain, a central pleckstrin homology (PH) domain, and
      a C-terminal phosphotyrosine binding (PTB) domain. Previous structural and
      biochemical studies have shown that the APPL BAR domains mediate homotypic and
      heterotypic APPL-APPL interactions and that the APPL1 BAR domain forms crescent
      shaped dimers. Although previous studies have shown that APPL minimal BAR domains
      associate with curved cell membranes, direct interaction between APPL BAR domains
      on cell membranes in vivo has not been reported. METHODOLOGY: Herein, we used a
      laser-scanning confocal microscope equipped with a spectral detector to carry out
      fluorescence resonance energy transfer (FRET) experiments with cyan fluorescent
      protein/yellow fluorescent protein (CFP/YFP) FRET donor/acceptor pairs to examine
      interactions between APPL minimal BAR domains at the subcellular level. This
      comprehensive approach enabled us to evaluate FRET levels in a single cell using
      three methods: sensitized emission, standard acceptor photobleaching, and
      sequential acceptor photobleaching. We also analyzed emission spectra to address
      an outstanding controversy regarding the use of CFP donor/YFP acceptor pairs in
      FRET acceptor photobleaching experiments, based on reports that photobleaching of
      YFP converts it into a CFP-like species. CONCLUSIONS: All three methods
      consistently showed significant FRET between APPL minimal BAR domain FRET pairs,
      indicating that they interact directly in a homotypic (i.e., APPL1-APPL1 and
      APPL2-APPL2) and heterotypic (i.e., APPL1-APPL2) manner on curved cell membranes.
      Furthermore, the results of our experiments did not show photoconversion of YFP
      into a CFP-like species following photobleaching, supporting the use of CFP
      donor/YFP acceptor FRET pairs in acceptor photobleaching studies.

PMID- 20814573
TI  - Stretch-induced stress fiber remodeling and the activations of JNK and ERK depend
      on mechanical strain rate, but not FAK.
AB  - BACKGROUND: Cells within tissues are subjected to mechanical forces caused by
      extracellular matrix deformation. Cells sense and dynamically respond to
      stretching of the matrix by reorienting their actin stress fibers and by
      activating intracellular signaling proteins, including focal adhesion kinase
      (FAK) and the mitogen-activated proteins kinases (MAPKs). Theoretical analyses
      predict that stress fibers can relax perturbations in tension depending on the
      rate of matrix strain. Thus, we hypothesized stress fiber organization and MAPK
      activities are altered to an extent dependent on stretch frequency. PRINCIPAL
      FINDINGS: Bovine aortic endothelial cells and human osteosarcoma cells expressing
      GFP-actin were cultured on elastic membranes and subjected to various patterns of
      stretch. Cyclic stretching resulted in strain rate-dependent increases in stress
      fiber alignment, cell retraction, and the phosphorylation of the MAPKs JNK, ERK
      and p38. Transient step changes in strain rate caused proportional transient
      changes in the levels of JNK and ERK phosphorylations without affecting stress
      fiber organization. Disrupting stress fiber contractile function with
      cytochalasin D or Y27632 decreased the levels of JNK and ERK phosphorylation.
      Previous studies indicate that FAK is required for stretch-induced cell alignment
      and MAPK activations. However, cyclic uniaxial stretching induced stress fiber
      alignment and the phosphorylation of JNK, ERK and p38 to comparable levels in FAK
      null and FAK-expressing mouse embryonic fibroblasts. CONCLUSIONS: These results
      indicate that cyclic stretch-induced stress fiber alignment, cell retraction, and
      MAPK activations occur as a consequence of perturbations in fiber strain. These
      findings thus shed new light into the roles of stress fiber relaxation and
      reorganization in maintenance of tensional homeostasis in a dynamic mechanical
      environment.

PMID- 20814574
TI  - Archaeological support for the three-stage expansion of modern humans across
      northeastern Eurasia and into the Americas.
AB  - BACKGROUND: Understanding the dynamics of the human range expansion across
      northeastern Eurasia during the late Pleistocene is central to establishing
      empirical temporal constraints on the colonization of the Americas. Opinions vary
      widely on how and when the Americas were colonized, with advocates supporting
      either a pre- or post- last glacial maximum (LGM) colonization, via either a land
      bridge across Beringia, a sea-faring Pacific Rim coastal route, a trans-Arctic
      route, or a trans-Atlantic oceanic route. Here we analyze a large sample of
      radiocarbon dates from the northeast Eurasian Upper Paleolithic to identify the
      origin of this expansion, and estimate the velocity of colonization wave as it
      moved across northern Eurasia and into the Americas. METHODOLOGY/PRINCIPAL
      FINDINGS: We use diffusion models to quantify these dynamics. Our results show
      the expansion originated in the Altai region of southern Siberia approximately
      46kBP , and from there expanded across northern Eurasia at an average velocity of
      0.16 km per year. However, the movement of the colonizing wave was not continuous
      but underwent three distinct phases: 1) an initial expansion from 47-32k calBP;
      2) a hiatus from approximately 32-16k calBP, and 3) a second expansion after the
      LGM approximately 16k calBP. These results provide archaeological support for the
      recently proposed three-stage model of the colonization of the Americas. Our
      results falsify the hypothesis of a pre-LGM terrestrial colonization of the
      Americas and we discuss the importance of these empirical results in the light of
      alternative models. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that the
      radiocarbon record of Upper Paleolithic northeastern Eurasia supports a post-LGM
      terrestrial colonization of the Americas falsifying the proposed pre-LGM
      terrestrial colonization of the Americas. We show that this expansion was not a
      simple process, but proceeded in three phases, consistent with genetic data,
      largely in response to the variable climatic conditions of late Pleistocene
      northeast Eurasia. Further, the constraints imposed by the spatiotemporal
      gradient in the empirical radiocarbon record across this entire region suggests
      that North America cannot have been colonized much before the existing Clovis
      radiocarbon record suggests.

PMID- 20814575
TI  - Serological response in RT-PCR confirmed H1N1-2009 influenza a by
      hemagglutination inhibition and virus neutralization assays: an observational
      study.
AB  - BACKGROUND: We describe the serological response following H1N1-2009 influenza A
      infections confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR).
      METHODOLOGY AND PRINCIPAL FINDINGS: The study included patients admitted to
      hospital, subjects of a seroepidemiologic cohort study, and participants
      identified from outbreak studies in Singapore. Baseline (first available blood
      sample) and follow-up blood samples were analyzed for antibody titers to H1N1
      2009 and recently circulating seasonal influenza A virus strains by
      hemagglutination inhibition (HI) and virus micro-neutralization (VM) assays. 267
      samples from 118 cases of H1N1-2009 were analyzed. Geometric mean titers by HI
      peaked at 123 (95% confidence interval, CI 43-356) between days 30 to 39. The
      chance of observing seroconversion (four-fold or greater increase of antibodies)
      was maximized when restricting analysis to 45 participants with baseline sera
      collected within 5 days of onset and follow-up sera collected 15 or more days
      after onset; for these participants, 82% and 89% seroconverted to
      A/California/7/2009 H1N1 by HI and VM respectively. A four-fold or greater
      increase in cross-reactive antibody titers to seasonal A/Brisbane/59/2007 H1N1,
      A/Brisbane/10/2007 H3N2 and A/Wisconsin/15/2009 H3N2 occurred in 20%, 18% and 16%
      of participants respectively. CONCLUSIONS AND SIGNIFICANCE: Appropriately timed
      paired serology detects 80-90% RT-PCR confirmed H1N1-2009; Antibodies from
      infection with H1N1-2009 cross-reacted with seasonal influenza viruses.

PMID- 20814576
TI  - In macrophages, caspase-1 activation by SopE and the type III secretion system-1
      of S. typhimurium can proceed in the absence of flagellin.
AB  - The innate immune system is of vital importance for protection against infectious
      pathogens. Inflammasome mediated caspase-1 activation and subsequent release of
      pro-inflammatory cytokines like IL-1beta and IL-18 is an important arm of the
      innate immune system. Salmonella enterica subspecies 1 serovar Typhimurium (S.
      Typhimurium, SL1344) is an enteropathogenic bacterium causing diarrheal diseases.
      Different reports have shown that in macrophages, S. Typhimurium may activate
      caspase-1 by at least three different types of stimuli: flagellin, the type III
      secretion system 1 (T1) and the T1 effector protein SopE. However, the relative
      importance and interdependence of the different factors in caspase-1 activation
      is still a matter of debate. Here, we have analyzed their relative contributions
      to caspase-1 activation in LPS-pretreated RAW264.7 macrophages. Using flagellar
      mutants (fliGHI, flgK) and centrifugation to mediate pathogen-host cell contact,
      we show that flagellins account for a small part of the caspase-1 activation in
      RAW264.7 cells. In addition, functional flagella are of key importance for
      motility and host cell attachment which is a prerequisite for mediating caspase-1
      activation via these three stimuli. Using site directed mutants lacking several
      T1 effector proteins and flagellin expression, we found that SopE elicits caspase
      1 activation even when flagellins are absent. In contrast, disruption of
      essential genes of the T1 protein injection system (invG, sipB) completely
      abolished caspase-1 activation. However, a robust level of caspase-1 activation
      is retained by the T1 system (or unidentified T1 effectors) in the absence of
      flagellin and SopE. T1-mediated inflammasome activation is in line with recent
      work by others and suggests that the T1 system itself may represent the basic
      caspase-1 activating stimulus in RAW264.7 macrophages which is further enhanced
      independently by SopE and/or flagellin.

PMID- 20814577
TI  - Abundance and diversity of dockerin-containing proteins in the fiber-degrading
      rumen bacterium, Ruminococcus flavefaciens FD-1.
AB  - BACKGROUND: The cellulosome is a multi-enzyme machine, which plays a key role in
      the breakdown of plant cell walls in many anaerobic cellulose-degrading
      microorganisms. Ruminococcus flavefaciens FD-1, a major fiber-degrading bacterium
      present in the gut of herbivores, has the most intricate cellulosomal
      organization thus far described. Cellulosome complexes are assembled through high
      affinity cohesin-dockerin interactions. More than two-hundred dockerin-containing
      proteins have been identified in the R. flavefaciens genome, yet the reason for
      the expansion of these crucial cellulosomal components is yet unknown.
      METHODOLOGY/PRINCIPAL FINDINGS: We have explored the full spectrum of 222
      dockerin-containing proteins potentially involved in the assembly of cellulosome
      like complexes of R. flavefaciens. Bioinformatic analysis of the various dockerin
      modules showed distinctive conservation patterns within their two Ca(2+)-binding
      repeats and their flanking regions. Thus, we established the conceptual framework
      for six major groups of dockerin types, according to their unique sequence
      features. Within this framework, the modular architecture of the parent proteins,
      some of which are multi-functional proteins, was evaluated together with their
      gene expression levels. Specific dockerin types were found to be associated with
      selected groups of functional components, such as carbohydrate-binding modules,
      numerous peptidases, and/or carbohydrate-active enzymes. In addition, members of
      other dockerin groups were linked to structural proteins, e.g., cohesin
      containing proteins, belonging to the scaffoldins. CONCLUSIONS/SIGNIFICANCE: This
      report profiles the abundance and sequence diversity of the R. flavefaciens FD-1
      dockerins, and provides the molecular basis for future understanding of the
      potential for a wide array of cohesin-dockerin specificities. Conserved
      differences between dockerins may be reflected in their stability, function or
      expression within the context of the parent protein, in response to their role in
      the rumen environment.

PMID- 20814578
TI  - A mechanistic model of PCR for accurate quantification of quantitative PCR data.
AB  - BACKGROUND: Quantitative PCR (qPCR) is a workhorse laboratory technique for
      measuring the concentration of a target DNA sequence with high accuracy over a
      wide dynamic range. The gold standard method for estimating DNA concentrations
      via qPCR is quantification cycle () standard curve quantification, which requires
      the time- and labor-intensive construction of a standard curve. In theory, the
      shape of a qPCR data curve can be used to directly quantify DNA concentration by
      fitting a model to data; however, current empirical model-based quantification
      methods are not as reliable as standard curve quantification. PRINCIPAL FINDINGS:
      We have developed a two-parameter mass action kinetic model of PCR (MAK2) that
      can be fitted to qPCR data in order to quantify target concentration from a
      single qPCR assay. To compare the accuracy of MAK2-fitting to other qPCR
      quantification methods, we have applied quantification methods to qPCR dilution
      series data generated in three independent laboratories using different target
      sequences. Quantification accuracy was assessed by analyzing the reliability of
      concentration predictions for targets at known concentrations. Our results
      indicate that quantification by MAK2-fitting is as reliable as standard curve
      quantification for a variety of DNA targets and a wide range of concentrations.
      SIGNIFICANCE: We anticipate that MAK2 quantification will have a profound effect
      on the way qPCR experiments are designed and analyzed. In particular, MAK2
      enables accurate quantification of portable qPCR assays with limited sample
      throughput, where construction of a standard curve is impractical.

PMID- 20814579
TI  - CD8+ T cells cause disability and axon loss in a mouse model of multiple
      sclerosis.
AB  - BACKGROUND: The objective of this study was to test the hypothesis that CD8+ T
      cells directly mediate motor disability and axon injury in the demyelinated
      central nervous system. We have previously observed that genetic deletion of the
      CD8+ T cell effector molecule perforin leads to preservation of motor function
      and preservation of spinal axons in chronically demyelinated mice.
      METHODOLOGY/PRINCIPAL FINDINGS: To determine if CD8+ T cells are necessary and
      sufficient to directly injure demyelinated axons, we adoptively transferred
      purified perforin-competent CD8+ spinal cord-infiltrating T cells into profoundly
      demyelinated but functionally preserved perforin-deficient host mice. Transfer of
      CD8+ spinal cord-infiltrating T cells rapidly and irreversibly impaired motor
      function, disrupted spinal cord motor conduction, and reduced the number of
      medium- and large-caliber spinal axons. Likewise, immunodepletion of CD8+ T cells
      from chronically demyelinated wildtype mice preserved motor function and limited
      axon loss without altering other disease parameters. CONCLUSIONS/SIGNIFICANCE: In
      multiple sclerosis patients, CD8+ T cells outnumber CD4+ T cells in active
      lesions and the number of CD8+ T cells correlates with the extent of ongoing axon
      injury and functional disability. Our findings suggest that CD8+ T cells may
      directly injure demyelinated axons and are therefore a viable therapeutic target
      to protect axons and motor function in patients with multiple sclerosis.

PMID- 20814580
TI  - Fire, fuel composition and resilience threshold in subalpine ecosystem.
AB  - BACKGROUND: Forecasting the effects of global changes on high altitude ecosystems
      requires an understanding of the long-term relationships between biota and
      forcing factors to identify resilience thresholds. Fire is a crucial forcing
      factor: both fuel build-up from land-abandonment in European mountains, and more
      droughts linked to global warming are likely to increase fire risks. METHODS: To
      assess the vegetation response to fire on a millennium time-scale, we analyzed
      evidence of stand-to-local vegetation dynamics derived from sedimentary plant
      macroremains from two subalpine lakes. Paleobotanical reconstructions at high
      temporal resolution, together with a fire frequency reconstruction inferred from
      sedimentary charcoal, were analyzed by Superposed Epoch Analysis to model plant
      behavior before, during and after fire events. PRINCIPAL FINDINGS: We show that
      fuel build-up from arolla pine (Pinus cembra) always precedes fires, which is
      immediately followed by a rapid increase of birch (Betula sp.), then by
      ericaceous species after 25-75 years, and by herbs after 50-100 years. European
      larch (Larix decidua), which is the natural co-dominant species of subalpine
      forests with Pinus cembra, is not sensitive to fire, while the abundance of Pinus
      cembra is altered within a 150-year period after fires. A long-term trend in
      vegetation dynamics is apparent, wherein species that abound later in succession
      are the functional drivers, loading the environment with fuel for fires. This
      system can only be functional if fires are mainly driven by external factors
      (e.g. climate), with the mean interval between fires being longer than the
      minimum time required to reach the late successional stage, here 150 years.
      CONCLUSION: Current global warming conditions which increase drought occurrences,
      combined with the abandonment of land in European mountain areas, creates ideal
      ecological conditions for the ignition and the spread of fire. A fire return
      interval of less than 150 years would threaten the dominant species and might
      override the resilience of subalpine forests.

PMID- 20814581
TI  - VASP: a volumetric analysis of surface properties yields insights into protein
      ligand binding specificity.
AB  - Many algorithms that compare protein structures can reveal similarities that
      suggest related biological functions, even at great evolutionary distances.
      Proteins with related function often exhibit differences in binding specificity,
      but few algorithms identify structural variations that effect specificity. To
      address this problem, we describe the Volumetric Analysis of Surface Properties
      (VASP), a novel volumetric analysis tool for the comparison of binding sites in
      aligned protein structures. VASP uses solid volumes to represent protein shape
      and the shape of surface cavities, clefts and tunnels that are defined with other
      methods. Our approach, inspired by techniques from constructive solid geometry,
      enables the isolation of volumetrically conserved and variable regions within
      three dimensionally superposed volumes. We applied VASP to compute a comparative
      volumetric analysis of the ligand binding sites formed by members of the
      steroidogenic acute regulatory protein (StAR)-related lipid transfer (START)
      domains and the serine proteases. Within both families, VASP isolated individual
      amino acids that create structural differences between ligand binding cavities
      that are known to influence differences in binding specificity. Also, VASP
      isolated cavity subregions that differ between ligand binding cavities which are
      essential for differences in binding specificity. As such, VASP should prove a
      valuable tool in the study of protein-ligand binding specificity.

PMID- 20814582
TI  - Plasticity of intermediate filament subunits.
AB  - Intermediate filaments (IFs) assembled in vitro from recombinantly expressed
      proteins have a diameter of 8-12 nm and can reach several micrometers in length.
      IFs assemble from a soluble pool of subunits, tetramers in the case of vimentin.
      Upon salt addition, the subunits form first unit length filaments (ULFs) within
      seconds and then assembly proceeds further by end-to-end fusion of ULFs and short
      filaments. So far, IF subunits have mainly been observed by electron microscopy
      of glycerol sprayed and rotary metal shadowed specimens. Due to the shear forces
      during spraying the IF subunits appear generally as straight thin rods. In this
      study, we used atomic force microscopy (AFM), cryo-electron microscopy (cryo-EM)
      combined with molecular modeling to investigate the conformation of the subunits
      of vimentin, desmin and keratin K5/K14 IFs in various conditions. Due to their
      anisotropic shape the subunits are difficult to image at high resolution by cryo
      EM. In order to enhance contrast we used a cryo-negative staining approach. The
      subunits were clearly identified as thin, slightly curved rods. However the
      staining agent also forced the subunits to aggregate into two-dimensional
      networks of dot-like structures. To test this conformational change further, we
      imaged dried unfixed subunits on mica by AFM revealing a mixture of extended and
      dot-like conformations. The use of divalent ions such as calcium and magnesium,
      as well as glutaraldehyde exposure favored compact conformations over elongated
      ones. These experimental results as well as coarse-grained molecular dynamics
      simulations of a vimentin tetramer highlight the plasticity of IF subunits.

PMID- 20814583
TI  - Intracellular DNA damage by lysine-acetylene conjugates.
AB  - Previously, we reported the design and properties of alkyne C-lysine conjugates,
      a powerful and tunable family of DNA cleaving reagents. We also reported that,
      upon photoactivation, these molecules are capable of inducing cancer cells death.
      To prove that the cell death stems from DNA cleavage by the conjugates, we
      investigated intracellular DNA damage induced by these molecules in LNCap cancer
      cells using single cell gel electrophoresis (SCGE) assays. The observation of
      highly efficient DNA damage confirmed that lysine acetylene conjugate is capable
      of cleaving the densely compacted intracellular DNA. This result provides a key
      mechanistic link between efficient DNA cleavage and cytotoxicity towards cancer
      cells for this family of light-activated anticancer agents.

PMID- 20814584
TI  - Nonparametric Mixture Models for Supervised Image Parcellation.
AB  - We present a nonparametric, probabilistic mixture model for the supervised
      parcellation of images. The proposed model yields segmentation algorithms
      conceptually similar to the recently developed label fusion methods, which
      register a new image with each training image separately. Segmentation is
      achieved via the fusion of transferred manual labels. We show that in our
      framework various settings of a model parameter yield algorithms that use image
      intensity information differently in determining the weight of a training subject
      during fusion. One particular setting computes a single, global weight per
      training subject, whereas another setting uses locally varying weights when
      fusing the training data. The proposed nonparametric parcellation approach
      capitalizes on recently developed fast and robust pairwise image alignment tools.
      The use of multiple registrations allows the algorithm to be robust to occasional
      registration failures. We report experiments on 39 volumetric brain MRI scans
      with expert manual labels for the white matter, cerebral cortex, ventricles and
      subcortical structures. The results demonstrate that the proposed nonparametric
      segmentation framework yields significantly better segmentation than state-of-the
      art algorithms.

PMID- 20814585
TI  - Convolution-Based Forced Detection Monte Carlo Simulation Incorporating Septal
      Penetration Modeling.
AB  - In SPECT imaging, photon transport effects such as scatter, attenuation and
      septal penetration can negatively affect the quality of the reconstructed image
      and the accuracy of quantitation estimation. As such, it is useful to model these
      effects as carefully as possible during the image reconstruction process. Many of
      these effects can be included in Monte Carlo (MC) based image reconstruction
      using convolution-based forced detection (CFD). With CFD Monte Carlo (CFD-MC),
      often only the geometric response of the collimator is modeled, thereby making
      the assumption that the collimator materials are thick enough to completely
      absorb photons. However, in order to retain high collimator sensitivity and high
      spatial resolution, it is required that the septa be as thin as possible, thus
      resulting in a significant amount of septal penetration for high energy
      radionuclides. A method for modeling the effects of both collimator septal
      penetration and geometric response using ray tracing (RT) techniques has been
      performed and included into a CFD-MC program. Two look-up tables are pre
      calculated based on the specific collimator parameters and radionuclides, and
      subsequently incorporated into the SIMIND MC program. One table consists of the
      cumulative septal thickness between any point on the collimator and the center
      location of the collimator. The other table presents the resultant collimator
      response for a point source at different distances from the collimator and for
      various energies. A series of RT simulations have been compared to experimental
      data for different radionuclides and collimators. Results of the RT technique
      matches experimental data of collimator response very well, producing correlation
      coefficients higher than 0.995. Reasonable values of the parameters in the lookup
      table and computation speed are discussed in order to achieve high accuracy while
      using minimal storage space for the look-up tables. In order to achieve noise
      free projection images from MC, it is seen that the inclusion of the RT
      implementation for septal penetration increases the speed of the simulation by a
      factor of about 7,500 compared to the conventional SIMIND MC program.

PMID- 20814586
TI  - Limitations in the Use of Fluorescein Diacetate/Propidium Iodide (FDA/PI) and
      Cell Permeable Nucleic Acid Stains for Viability Measurements of Isolated Islets
      of Langerhans.
AB  - BACKGROUND: A review of current literature shows that the combined use of the
      cell permeable esterase-substrate fluorescein diacetate (FDA) and the cell
      impermeant nucleic acid stain propidium iodide (PI) to be one of the most common
      fluorescence-based methods to assess the viability of isolated islets of
      Langerhans, and it is currently used for islet product release prior to
      transplantation in humans. However, results from this assay do not correlate with
      islet viability and function or islet transplantation success in animals or
      humans (Eckhard et al. 2004; Ricordi et al. 2001). This may be in part attributed
      to considerable differences as well as discrepancies in the use of these reagents
      on islets. We critically surveyed the literature and evaluated the impact of a
      number of variables associated with the use of FDA/PI to determine their
      reliability in assessing islet cell viability. In addition, we evaluated other
      fluorescent stains, such as SYTO(R)13, SYTO(R)24 and SYBR(R)14 as possible
      alternatives to FDA. RESULTS: We found that the stability of stains in storage
      and stock solutions, the number of islets stained, concentration of stains,
      staining incubation time, the buffer/media used, and the method of examining
      islets were significant in the final scoring of viability. For archival file
      photos, the exposure time and camera/software settings can also impact
      interpretation of viability. Although our results show that FDA does detect
      intracellular esterase activity and staining with PI does assess cell membrane
      integrity, the results obtained from using these stains did not correlate
      directly with expected islet function and viability per transplantation into
      diabetic athymic nude mice (Papas et al. 2007). In addition, the use of two
      nucleic acid stains, such as SYTO(R)13 and PI, for live/dead scoring exhibited
      staining anomalies which limit their accuracy in assessing islet viability.
      CONCLUSIONS: From a review of the literature and from our observations on the
      impact of reagent handling and various staining and imaging parameters used to
      visually evaluate islets, consistent interpretation of islet cell membrane
      integrity and viability is dependent upon a number of factors. We discuss the
      utility and limitations of these reagents in evaluating islet cell membrane
      integrity and viability.

PMID- 20814587
TI  - Chronicle of a Myth Foretold: The Washington Consensus in Latin America.

PMID- 20814589
TI  - The Geography of Undocumented Mexican Migration.
AB  - Using data from Mexico's Matricula Consular program, we analyze the geographic
      organization of undocumented Mexican migration to the United States. We show that
      emigration has moved beyond its historical origins in west-central Mexico into
      the central region and, to a lesser extent, the southeast and border regions. In
      the United States, traditional gateways continue to dominate, but a variety of
      new destinations have emerged. California, in particular, has lost its
      overwhelming dominance. Although the geographic structure of Mexico-U.S.
      migration is relatively stable, it has nonetheless continued to evolve and change
      over time.

PMID- 20814588
TI  - Existence of seven human IL-1R1 promoters.
AB  - Previous studies have reported the existence of three promoters for the human
      type I interleukin-1 receptor (hIL-1R1) gene. These promoters were discovered by
      identifying discrete transcription start sites (TSS) from limited human cell
      lines. In this study, we examined the TSSs of hIL-1R1 mRNA from 24 different
      tissues and identified several novel TSSs in hIL-1R1 that suggest the existence
      of seven hIL-1R1 promoters: three of them are the same as those reported
      previously and four are putative novel promoters. Using a promoter-reporter
      assay, we show here that these promoters can drive the transcription of the
      reporter gene. In addition, these promoters exhibit cell type specific expression
      patterns and they can be regulated by enhancer elements in a cell type specific
      manner. Only one of the promoters was found to be sensitive to the stimulation by
      glucocorticoids. Similar to our recent report on murine IL-1R1, two of the hIL
      1R1 promoters appear to be the dominant promoters, one of which was published
      previously and the other is identified in the present study. We also found an
      internal promoter that drives the expression of IL-1R1 after the conventional
      translation start codon, suggesting that a truncated hIL-1R1 may be expressed by
      this promoter. These results provide additional information regarding the
      transcription of hIL-1R1.

PMID- 20814590
TI  - Racial Formation in Theory and Practice: The Case of Mexicans in the United
      States.
AB  - Mechanisms of social stratification require the categorical definition of an out
      group to that can be excluded and exploited. Historically, in the United States,
      African Americans have been the subject of a systematic process of racial
      formation to define socially in this fashion. Beginning in the 1970s, however,
      and accelerating in the 1980s and 1990s, Mexicans were increasingly subject to
      processes of racialization that have rendered them more exploitable and
      excludable than ever before. Over the past decade, Mexican Americans moved
      steadily away from their middle position in the socioeconomic hierarchy and
      gravitated toward the bottom. This paper describes the basic mechanisms of
      stratification in the United States and how Mexicans have steadily been
      racialized to label them socially as a dehumanized and vulnerable out-group.

PMID- 20814591
TI  - New World Orders: Continuities and Changes in Latin American Migration.
AB  - Although migration from Mexico to the United States is more than a century old,
      until recently most other countries in Latin America did not send out significant
      numbers of migrants to foreign destinations. Over the past thirty years, however,
      emigration has emerged as an important demographic force throughout the region.
      This article outlines trends in the volume and composition of the migrant
      outflows emanating from various countries in Latin America, highlighting their
      diversity with respect to country of destination; multiplicity of destinations;
      legal auspices of entry; gender and class composition; racial, ethnic, and
      national origins; and the mode of insertion into the receiving society. The
      review underscores the broadening of international migration away from
      unidirectional flows toward the United States to new streams going to Europe,
      Canada, Australia, and Japan, as well as to other countries in Latin America
      itself.

PMID- 20814592
TI  - The role of constitutively activated STAT3 in B16 melanoma cells.
AB  - Constitutively activated STAT3 is found frequently in a wide variety of human
      tumors, including melanoma. Moreover, constitutive STAT3 activation actively
      participates in tumor formation and progression, making STAT3 an attractive
      target for cancer therapy. We report here that in murine B16 melanoma cells,
      which have been previously shown to express constitutively active STAT3, the
      expression of a mutant form of STAT3 with the canonical tyrosine phosphorylation
      site (residue 705) mutated to phenylanaine has dominant-negative properties
      (STAT3-DN). STAT3-DN inhibits STAT3 tyrosine phosphorylation and STAT3-dependent
      DNA binding activity. Most importantly, STAT3-DN expression in B16 cells inhibits
      their invasiveness, as well as their melanogenesis by down-regulation of
      tyrosinase mRNA and protein expression as well as tyrosinase activity. These
      results suggest that STAT3 signaling plays a critical role in regulating melanoma
      behavior, and may represent a druggable target for melanoma therapy.

PMID- 20814593
TI  - Performance of a Whole-Blood Interferon-Gamma Release Assay with Mycobacterium
      RD1-Specific Antigens among HIV-Infected Persons.
AB  - OBJECTIVE: To evaluate the usefulness of one of IGRAs, QuantiFERON-TB Gold (QFT
      G), in human immunodeficiency virus- (HIV-) infected patients with various CD4(+)
      T cell counts. METHODS: The QFT-G assay was performed using QFT-G kits among 107
      HIV-infected patients including 9 cases with active tuberculosis (TB). RESULTS:
      In HIV-infected patients with CD4(+) > 50/microL, QFT-G positive rate for active
      TB patients was 5/6 (sensitivity = 83%), and that for those without active
      disease was 1/69 (specificity = 99%). The frequency of indeterminate QFT-G test
      was significantly higher in those with CD4(+) less than 50/microL (P < .0001). At
      the same time there was a proportional relationship between CD4(+) and interferon
      gamma response to mitogen (positive control) in QFT-G test (P = .0001).
      Conclusions. Our data suggested that QFT-G had high sensitivity and specificity
      in HIV-infected populations with CD4(+) greater than 50/microL. However, QFT-G
      did not perform well in HIV-positive patients with CD4(+) less than 50/microL.

PMID- 20814594
TI  - Telemedical support in patients with chronic heart failure: experience from
      different projects in Germany.
AB  - The great epidemiological significance and costs associated with chronic heart
      failure pose a challenge to health systems in Western industrial countries. In
      the past few years, controlled randomised studies have shown that patients with
      chronic heart failure benefit from telemedical monitoring; specifically,
      telemonitoring of various vital parameters combined with a review of the
      symptoms, drug compliance and patient education. In Germany, various telemedical
      monitoring projects for patients with chronic heart failure have been initiated
      in the past few years; seven of them are presented here. Currently 7220 patients
      are being monitored in the seven selected projects. Most patients (51.1%) are in
      NYHA stage II, 26.3% in NYHA stage III, 14.5% in NYHA stage I and only 6.6% in
      NYHA stage IV respectively. Most projects are primarily regional. Their structure
      of telemedical monitoring tends to be modular and uses stratification according
      to the NYHA stages. All projects include medical or health economics assessments.
      The future of telemedical monitoring projects for patients with chronic heart
      failure will depend on the outcome of these assessments. Only of there is
      statistical evidence for medical benefit to the individual patient as well as
      cost savings will these projects continue.

PMID- 20814595
TI  - Acute adrenal crisis in an asthmatic child treated with inhaled fluticasone
      proprionate.
AB  - Adrenal suppression secondary to prolonged inhaled corticosteroid use is usually
      limited to biochemical abnormalities, with no obvious clinical effects. Acute
      adrenal crisis is much rarer event but has been reported with increasing
      frequency. We report a case of a 7-year-old asthmatic child who presented with an
      acute history of lethargy after a respiratory infection. He was maintained on 220
      mug/day of fluticasone propionate for several years. Initial evaluation revealed
      severe adrenal suppression, with undetectable cortisol levels and minimal
      response after stimulation with ACTH. After fluticasone was discontinued, a
      gradual recovery of the adrenal axis was seen. This case shows that acute adrenal
      crisis may be a consequence even at the usual prescribed doses, stressing the
      importance of using the lowest dose of inhaled steroids needed to control
      symptoms and having an increased awareness of this complication.

PMID- 20814596
TI  - Postdural puncture headache.
AB  - Postdural puncture headache (PDPH) has been a problem for patients, following
      dural puncture, since August Bier reported the first case in 1898. His paper
      discussed the pathophysiology of low-pressure headache resulting from leakage of
      cerebrospinal fluid (CSF) from the subarachnoid to the epidural space. Clinical
      and laboratory research over the last 30 years has shown that use of small-gauge
      needles, particularly of the pencil-point design, is associated with a lower risk
      of PDPH than traditional cutting point needle tips (Quincke-point needle). A
      careful history can rule out other causes of headache. A postural component of
      headache is the sine qua non of PDPH. In high-risk patients , for example, age <
      50 years, postpartum, large-gauge needle puncture, epidural blood patch should be
      performed within 24-48 h of dural puncture. The optimum volume of blood has been
      shown to be 12-20 mL for adult patients. Complications of AEBP are rare.

PMID- 20814597
TI  - Short-term cardiac and noncardiac mortality following liver transplantation.
AB  - Objectives. To determine the importance of acute cardiac events as a cause of
      mortality compared to non-cardiac events in the four month period following liver
      transplantation (LT) using current preoperative cardiac screening strategies.
      Patients and Methods. We retrospectively reviewed timing, type, and outcome of
      adverse cardiac events, and all cause mortality in the 4 month postoperative
      period in 393 consecutive LT patients from October 1999 to February 2008.
      Results. Of 30 total deaths (7.6% overall mortality rate), 27 (90%) were due to
      surgical or medical complications and 3 (10%) were primary cardiac deaths (0.8%
      cardiac mortality rate). Acute cardiac events occurred in 26 patients (6.6%),
      including 13 arrhythmias (50%), 7 new onset heart failures (27%), and 6
      myocardial infarctions (23%). Twelve of 13 intraoperative events were arrhythmias
      (92%) including two of three cardiac deaths. Conclusions. Using current
      preoperative screening recommendations, deaths from primary cardiac events within
      four months of LT are very uncommon (0.8%), especially compared with deaths
      related to medical and surgical complications (6.9%).

PMID- 20814598
TI  - Immediate implants and immediate loading in periodontally compromised patients-a
      3-year prospective clinical study.
AB  - To avoid the necessity of a removable provisional prosthesis, and therefore
      preserve the patient's functional outcome, esthetics, and quality of life, a
      clinical protocol was developed to approach periodontally compromised patients
      presenting a full-arch irreversibly lost dentition: full-arch extraction and
      immediate replacement with a provisional acrylic resin implant-supported fixed
      partial denture (FPD). A total of 23 periodontally compromised patients (11
      women, 12 men; 4 smokers, 4 controlled diabetics) were included in this study.
      Pretreatment casts were taken and vertical dimension of occlusion was determined.
      In most patients, 6 Straumann implants were distributed along the arch according
      to the surgical guide or bone availability, with the most distal ones in the
      maxilla slightly tilted so they could emerge more distally. A total of 168
      implants (146 Straumann, 10 Nobel Biocare, 8 Biomet 3i, and 4 Lifecore) were
      placed (83 in the maxilla, 85 in the mandible). Of those in the maxilla, 74 were
      loaded immediately (implant stability quotient mentor [ISQm] > 70) and 9 placed
      with delayed loading (ISQm =/< 70). Of the 85 implants placed in the mandible,
      all were loaded immediately (ISQm > 70). If an FPD had not been fabricated
      already, impressions were taken during surgery to do so. The prosthesis was then
      adapted (cemented or screwed) to the 6 implants within the first 48 hours
      postsurgery. After 2 months, definitive impressions were taken, and a definitive
      porcelain-fused-to-metal implant-supported 12-element FPD was fabricated and
      cemented or screwed to all 6 implants. Of the 168 implants, 108 were immediate
      implants and 159 immediately loaded. Only 2 implants (1 in the mandible, 1 in the
      maxilla) did not osseointegrate. This yields a 3-year cumulative survival rate of
      98.74% (98.65% in the maxilla, 98.82% in the mandible). From a total of 26
      immediately loaded prostheses (12 in the maxilla, 14 in the mandible), 6 were
      cemented and 20 screw-retained. The 3-year cumulative survival rate was 100%.
      Immediate loading in mandibular and maxillary periodontally compromised patients
      presents itself as a predictable technique with a 100% cumulative survival rate
      for provisional and definitive prosthetic rehabilitations.

PMID- 20814599
TI  - A pilot experimental lateral ridge augmentation study using bone morphogenetic
      protein 2 in dogs.
AB  - The loss of multiple teeth in the posterior mandible often results in deficient
      ridge width for prosthetic tooth rehabilitation. Multiple approaches have been
      used to regenerate lost bone; however, the outcomes are highly variable. Several
      approaches use combination therapy to make the procedure more predictable. In
      this experimental study in dogs, a chronic defect was created and then treated
      with one of four therapies: (1) autograft, (2) recombinant human bone
      morphogenetic protein 2 (rhBMP-2) in absorbable collagen sponge (ACS), (3) ACS
      wrapped around a collagen-ceramic matrix, and (4) rhBMP-2 in ACS around the
      collagen-ceramic matrix. Two metal screws were used for space maintenance. After
      2 months, the metal pins were removed and an endosseous dental implant was placed
      in the regenerated bone. Two months later, the animals were sacrificed and
      specimens prepared for histologic evaluation. Only five animals were used, with
      each condition evaluated in each animal. With this low number of animals and with
      the observed variability, no quantitative differences were found between each of
      the four conditions evaluated. All conditions resulted in new bone growth. Dense
      native bone was found in the autograft sites and the sites treated with rhBMP-2
      and ACS. Sites treated with the collagen-ceramic matrix with and without rhBMP-2
      in the ACS had residual ceramic and large porous areas. Bone was found in varying
      degrees along the implant surfaces. These results suggest that multiple
      approaches can be used to augment bone horizontally in the posterior mandible of
      dogs. Interestingly, rhBMP-2 combined with a non-space maintaining collagen
      carrier yielded new bone densities similar to the autograft in this model.

PMID- 20814600
TI  - Proximal contact areas of the maxillary anterior dentition.
AB  - The goal of this study was to quantify the apicoincisal extent of the proximal
      contact area (PCA) between the eight maxillary anterior teeth. A total of 140 PCA
      sites and 160 crown lengths were measured in 20 healthy patients. The percentage
      ratio of PCA to clinical crown length was computed and defined as the proximal
      contact area proportion (PCAP). Mean PCA dimensions between central incisors
      (CI/CI), central and lateral incisors (CI/LI), lateral incisors and canines
      (LI/CA), and canines and first premolars (CA/PM) were 4.2, 2.9, 2.0, and 1.5 mm,
      respectively. Mesial mean PCAPs were 41%, 32%, 20%, and 18%, respectively. The
      paired sample t test demonstrated significant differences between all PCAs (P <
      .0001), except for CA/PM sites (P = .24). Contact areas, not contact points, were
      observed between neighboring maxillary anterior teeth. Natural PCAPs emerged as
      well defined in the maxillary anterior dentition bilaterally. Therefore, PCAPs
      should be taken into consideration for clinical anterior restorations since they
      determine the papillary and incisal embrasures.

PMID- 20814601
TI  - Subpapillary continuous sling suturing method for soft tissue grafting with the
      tunneling technique.
AB  - This paper describes a new suturing method, the subpapillary continuous sling
      suture, for use with soft tissue grafts in tunnel procedures to treat gingival
      recession. This method combines the graft suture and the sutures used to advance
      the pouch margins over the graft into a single continuous sling suture. It is
      indicated particularly for sites with shallow recessions and those treated for
      augmentation rather than root coverage because of a lack of graft access for
      standard suture placement. The single-suture method may also be used for sites
      with moderate to severe recession. The advantages of this method include
      elimination of the need to place additional sutures for coronal advancement of
      the pouch, resulting in reduced suturing time and reduced opportunity to
      inadvertently cut the continuous suture with the needle when suturing the pouch.

PMID- 20814602
TI  - Rapid treatment of Class II malocclusion with piezocision: two case reports.
AB  - An increasing number of adult patients are seeking orthodontic treatment to
      enhance their smile or their masticatory function. In this fast-paced and self
      conscious society, time and esthetics have become increasingly important. One of
      the biggest challenges an adult orthodontic patient faces is the time spent
      wearing brackets. Over the years, several surgical techniques have been developed
      to address this issue and reduce overall treatment time. Although very effective,
      these techniques have proven to be quite invasive. A new, minimally invasive
      procedure (piezocision) is presented that combines microincisions and localized
      piezoelectric surgery to achieve similar results rapidly and with minimal trauma.

PMID- 20814603
TI  - The controlled assisted ridge expansion technique for implant placement in the
      anterior maxilla: a technical note.
AB  - This technical report describes the simple and valuable technique of controlled
      assisted ridge expansion (CARE) for the esthetic zone of the anterior maxilla.
      Atrophic bone and narrow alveolar crests make implant bed preparation difficult.
      The highly predictable surgical technique of CARE for alveolar expansion uses
      periosteal containment and subperiosteal intrabony vertical releasing incisions
      efficiently. This allows for the expansion of narrow, anatomically limiting
      edentulous ridges. The precise and conservative use of Piezosurgery and assisted
      manipulation of the labialized bony pedicle by horizontal spreaders and rotary
      osteocondensers affords a highly predictable surgical procedure, which allows
      implants to be placed at the time of surgery, reducing patient treatment time,
      morbidity, functional losses, and overall cost, as well as increasing the native
      bone volume in the atrophic maxillary ridge.

PMID- 20814604
TI  - Three-dimensional bone and soft tissue requirements for optimizing esthetic
      results in compromised cases with multiple implants.
AB  - Achieving an esthetic outcome in tooth replacement and implant treatment requires
      a proper tooth shape and stable surrounding soft tissue profiles. Bone
      augmentation is considered vital to support the esthetic soft tissue profile
      around definitive restorations. To prevent recession of the peri-implant soft
      tissue in cases with multiple implants, buccal bone augmentation of more than 2
      mm from the implant platform is necessary to overcome the normal pattern of bone
      remodeling. Drawing an imaginary horizontal line spanning the space between the
      remaining healthy interproximal bone peaks is the most reliable vertical
      augmentation target to create esthetic papillae around an implant prosthesis.
      Provided that the adjacent bone peaks are at an ideal height and the bone is
      augmented vertically up to this line, the accepted general guideline of 2 to 3 mm
      of interproximal vertical bone augmentation from ideally placed implant platforms
      will invariably also be achieved. In addition, placing pontics in strategic
      positions to avoid consecutively placed implants has been suggested to facilitate
      vertical bone height preservation after bone augmentation. Even with esthetically
      successful results, there have been very few long-term studies on compromised
      cases with multiple implants. This will become more and more critical over time
      and must be remedied.

PMID- 20814605
TI  - A modified tensionless gingival grafting technique using acellular dermal matrix.
AB  - Conventional surgical procedures designed for autogenous tissue material may not
      be appropriate when using acellular dermal matrix (ADM) for the treatment of
      gingival recessions. This article describes a new surgical technique that
      addresses the unique and sensitive aspects of ADM specifically to improve
      esthetic outcomes and gain increased clinical predictability when treating Miller
      Class I and II gingival recession defects. In this paper, a root coverage case is
      described and the specific steps and rationale for this new technique are
      explained. This technique has been predictable clinically, with results
      comparable to those achieved using autogenous tissue.

PMID- 20814606
TI  - An interarch alveolar ridge relationship classification.
AB  - Alveolar ridge defects resulting from tooth loss, trauma, periodontal disease, or
      congenital lesions often require correction prior to dental implant therapy.
      Numerous classifications proposed to describe alveolar ridge defects have been
      limited to describe intra-arch relationships. To provide sufficient jaw-to-jaw
      alveolar ridge (interarch) relationship information for both restorative and
      surgical treatment decision-making, this article introduces a new interarch
      alveolar ridge relationship classification system. This article also discusses
      cone beam computed tomography and multidisciplinary treatment planning options
      for approaching each classification.

PMID- 20814615
TI  - In this issue: Reverse translation.

PMID- 20814616
TI  - In this issue: Comments on the proposed term pleomorphic ichthyosis.

PMID- 20814617
TI  - In this issue: Rapid categorization of mild types of autosomal recessive
      congenital ichthyosis undergoing a phenotypic shift: should it be called
      "pleomorphic ichthyosis" or "congenital ichthyosis with mild scaling (CIMS)"?

PMID- 20814618
TI  - Pleomorphic ichthyosis: proposed name for a heterogeneous group of congenital
      ichthyoses with phenotypic shifting and mild residual scaling.
AB  - Congenital ichthyosis is often associated with typical neonatal phenotypes,
      "Collodion baby" and "Harlequin foetus", later transforming into severe lamellar
      or erythrodermic ichthyosis. However, in a minority of cases the skin condition
      will improve spontaneously after birth, although slight scaling, xerosis,
      hypohidrosis and keratoderma usually persist. Some of these patients will
      eventually be diagnosed as suffering from self-improving collodion ichthyosis,
      ichthyosis prematurity syndrome, or other, even rarer, forms of ichthyosis also
      characterized by a phenotypic shift in early childhood. This paper summarizes
      newly described aetiologies for some of these diseases and discusses difficulties
      encountered when trying to distinguish them clinically from other types of
      autosomal recessive congenital ichthyosis. To remind health providers about this
      heterogeneous group of partially transient disorders of cornification, a new
      umbrella term, "pleomorphic ichthyosis", is proposed.

PMID- 20814619
TI  - Guidelines for the laboratory diagnosis of mycoplasma genitalium infections in
      East European countries.
AB  - The present guidelines aim to provide comprehensive information regarding
      laboratory diagnosis of Mycoplasma genitalium infections in East European
      countries. These guidelines are intended primarily for laboratory professionals
      testing specimens from patients at sexual health care clinics, but may also be
      useful for community-based screening programmes. Diagnosis of M. genitalium
      infection is performed exclusively using nucleic acid amplification tests
      (NAATs), owing to the poor and slow growth of the bacterium in culture. Because
      no internationally validated and approved commercial NAAT for M. genitalium
      detection is presently available, it is necessary that laboratories performing M.
      genitalium diagnostics not only carefully evaluate and validate their in-house
      PCRs before using them routinely, but also use comprehensive internal controls
      and take part in external quality assessment programmes. The guidelines were
      elaborated as a consensus document of the Eastern European Sexual and
      Reproductive Health (EE SRH) Network, and comprise one element of a series of
      guidelines aimed at optimizing, standardizing, and providing guidance on quality
      laboratory testing for reproductive tract infections.

PMID- 20814620
TI  - In vitro propagation and dynamics of T cells from skin biopsies by methods using
      interleukins-2 and -4 or anti-CD3/CD28 antibody-coated microbeads.
AB  - In order to explore the mechanisms of inflammatory skin disorders, we established
      two methods of expanding skin-derived lymphocytes, one using high levels of
      interleukin (IL)-2 and IL-4 (method A) and the other using low levels of
      cytokines and anti-CD3/CD28 microbeads (method B). Both methods provide
      advantages for functional studies. With either of these two, we could obtain more
      than 10(7) cells/ from a 3 mm skin biopsy in 21 days from 23 out of 26 biopsies
      of various skin diseases. The relevance of these cells was confirmed by shifted T
      cell receptor beta chain variable region (TCR-Vbeta) repertoire and antigen
      dependent proliferation in antigen-driven skin disorders. The propagation of skin
      resident lymphocytes, seen especially in method A, seems to be mediated by a
      functional defect of regulatory T cells residing in skin sequentially expanding
      under the conditions of our methods.

PMID- 20814622
TI  - Routine diagnostic patch-testing with formaldehyde 2.0% (0.6 mg/cm2) may be an
      advantage compared to 1.0%.
AB  - Our clinical experience has suggested that the presently recommended patch-test
      concentration (1.0%) for formaldehyde in the baseline series might be too low.
      Therefore, consecutively patch-tested dermatitis patients were tested
      simultaneously with formaldehyde 1.0% and 2.0% (w/v) in aqua. Formaldehyde 1.0%
      and 2.0% were applied with a micro-pipette (15 microl) to filter paper discs in
      Finn Chambers (0.30 mg/cm(2) and 0.60 mg/cm(2), respectively). A total of 1397
      patients with dermatitis were patch-tested. In all, 68 (4.9%) patients reacted
      positively to formaldehyde; 37 reacted only to 2.0%, 29 reacted to both
      concentrations, and 2 reacted only to 1.0%. Significantly more patients were thus
      diagnosed with contact allergy to formaldehyde 2.0% compared with 1.0% (p <
      0.001). We detected 0.1%, 0.4%, and 29.6% irritant reactions to 1.0%, 2.0%, and
      3.0% formaldehyde, respectively. We conclude that, with an optimized patch-test
      technique, doubling the dose per area detects significantly more contact
      allergies to formaldehyde, but an even higher test concentration causes too many
      irritant reactions to be usable.

PMID- 20814621
TI  - Skin cancer risk among solid organ recipients: a nationwide cohort study in
      Denmark.
AB  - This study assessed the risk of skin cancer following transplantation of 4 types
      of solid organs, and the risk of skin cancer in patients with chronic diseases
      that lead to organ transplantations. A population-based cohort of 5279 Danish
      patients who underwent heart, lung, renal and liver transplantation, and 77,782
      patients with chronic heart, lung, renal and liver diseases during 1977-2006 were
      included in the study. Linkage to the Danish Cancer Registry allowed complete
      follow-up for basal cell carcinoma, squamous cell carcinoma and malignant
      melanoma. Standardized incidence ratios (SIR) and 95% confidence intervals (CI)
      were calculated. The SIR for squamous cell carcinoma was highest among heart (SIR
      = 113; 95% CI: 74-166), then renal (SIR = 81; 95% CI: 68-96), lung (SIR = 65; 95%
      CI: 28-128) and liver (SIR = 60; 95% CI: 27-113) recipients. SIR for squamous
      cell carcinoma was 4.8 (95% CI: 2.2-9.0) among renal failure patients, but not
      greatly elevated among patients with the other chronic diseases studied. Organ
      transplantation is a risk factor for squamous cell carcinoma, with
      immunosuppressive treatments being the most likely explanation for the
      association.

PMID- 20814623
TI  - A comparative study of dyslipidaemia in men and woman with androgenic alopecia.
AB  - Several studies have analyzed the relationship between androgenetic alopecia and
      cardiovascular disease (mainly heart disease). However few studies have analyzed
      lipid values in men and women separately. This case-control study included 300
      patients consecutively admitted to an outpatient clinic, 150 with early onset
      androgenetic alopecia (80 males and 70 females) and 150 controls (80 males and 70
      females) with other skin diseases. Female patients with androgenic alopecia
      showed significant higher triglycerides values (123.8 vs 89.43 mg/dl, p = 0.006),
      total cholesterol values (196.1 vs 182.3 mg/dl, p = 0.014), LDL-C values (114.1
      vs 98.8 mg/dl, p = 0.0006) and lower HDL-C values (56.8 vs 67.7 mg/dl, p <0.0001)
      versus controls respectively. Men with androgenic alopecia showed significant
      higher triglycerides values (159.7 vs 128.7 mg/dl, p = 0.04) total cholesterol
      values (198.3 vs 181.4 mg/dl, p = 0.006) and LDL-C values (124.3 vs 106.2, p =
      0.0013) versus non-alopecic men. A higher prevalence of dyslipidemia in women and
      men with androgenic alopecia has been found. The elevated lipid values in these
      patients may contribute, alongside other mechanisms, to the development of
      cardiovascular disease in patient with androgenic alopecia.

PMID- 20814624
TI  - High body mass index in adolescent girls precedes psoriasis hospitalization.
AB  - Psoriasis is associated with being overweight, but the temporal relationship is
      not known. This historical cohort study tested whether severe psoriasis resulting
      in hospitalization in adulthood was preceded by excess increase in age-adjusted
      body mass index, a known risk factor in childhood for being overweight in
      adulthood. The study cohort was based on the Copenhagen School Health Records
      Register, birth years 1930 to 1984 (309,152 schoolchildren). Cases were found
      through the Danish National Patient Register for the period 1977 to 2001. A total
      of 1074 (0.36%) of the schoolchildren were identified as having psoriasis, with
      at least one hospital admission. Multivariate analysis demonstrated an
      association between excess increase in body mass index and psoriasis in females
      only. Being overweight in adolescence was the main factor behind this
      observation. The female group showed a significant association between psoriasis
      and body mass index at ages 12 (p = 0.028) and 13 years (p = 0.010). This was not
      the case for males or for body mass index measured at ages 11 years and below.

PMID- 20814625
TI  - Not all intravenous immunoglobulin preparations are equally well tolerated.
AB  - Intravenous immunoglobulin (IVIG) is used for many indications beyond the
      original substitution in primary antibody deficiency. Whereas many reports
      mention adverse reactions, no comparative data exist concerning the incidence of
      side-effects among the different brands of IVIG. We describe here our experience
      with the use of different IVIG formulations and their tolerability in a select
      cohort of 40 patients. The IVIG dose ranged from 0.4 to 3 g/kg/day and was given
      for 1-2742 days. Fourteen patients (35%) experienced mild to severe adverse
      reactions during or within 48 h of administration of standard IVIG preparation,
      which did not recur after switching to an alternative preparation. Adverse
      reactions included headache, fever, chills, nausea, emesis, hypotension and
      muscle cramps. One patient experienced a severe adverse reaction; he had a 3-day
      headache following IVIG infusion. Among the 16 patients who received alternative
      preparation initially, none experienced adverse reactions. In conclusion, this
      study shows that IVIG preparations are not all equally well tolerated in
      patients. The data suggest that, perhaps to a comparable extent to the
      preparation itself, the infusion rate has a major effect. If a reduction in the
      infusion rate does not minimize side-effects, one should consider switching the
      IVIG formulation.

PMID- 20814626
TI  - Hydroa vacciniforme with mucosal involvement and recalcitrant periodontitis and
      multiple virus re-activators after sun-exposure.
AB  - An 8-year-old boy presented with hydroa vacciniforme with recurrent oral mucosal
      ulcers and treatment-resistant gingivitis/periodontitis. Symptoms of oral mucosal
      involvement and gingivitis/periodontitis mirrored the severity of the skin
      lesions in sun-exposed areas. Although Epstein-Barr virus was negative in the
      skin lesions, Epstein-Barr virus DNA was detected in the gingival lesions when
      skin disease activity increased. Human herpes viruses-6 and -7 were also positive
      in the gingival lesions. Notably, human parvovirus B19 DNA was detected in both
      skin and gingival lesions. Impairment of systemic immunity was not detected. This
      report describes a rare case of hydroa vacciniforme with mucosal involvement and
      periodontal disease accompanied by multiple local virus re-activation.

PMID- 20814627
TI  - Ectopic extramammary Paget's disease: case report and literature review.
AB  - Extramammary Paget's disease that occurs in non-apocrine-bearing regions is
      referred to as ectopic and has been rarely reported. A 62-year-old man presented
      with a slowly progressive, asymptomatic light-brown plaque on his back.
      Histopathological examination revealed the presence of large pale cells with
      prominent nuclei, which proliferated diffusely and focally in the epidermis.
      Immuno-histochemically the tumour cells were positive for CK7, GCDFP-15, CEA, and
      p63. Based on these findings, we diagnosed the tumour as ectopic extramammary
      Paget's disease. We reviewed the English and Japanese literature and found 29
      previously reported cases of ectopic extramammary Paget's disease, including our
      case, with a predominance of occurrence in the Asian population. The germinative
      milk line is known to be a possible site where extramammary Paget's disease
      occurs. Like-wise, some germinative apocrine-differentiating cells might exist on
      the trunk preferentially in Asians. Attention should be paid to the development
      of ectopic as well as triple or quadruple EMPD in Asians.

PMID- 20814628
TI  - The overall agreement of proposed definitions of mucopurulent cervicitis in women
      at high risk of Chlamydia infection.
AB  - The overall agreement between different criteria for cervicitis in women infected
      with Chlamydia trachomatis and/or Mycoplasma genitalium, and in women who tested
      negative was examined. Women attending a clinic for sexually transmitted diseases
      were enrolled because of sexual partners' suspected chlamydia infection. M.
      genitalium was tested in a sample of first-catch urine and an endocervical
      specimen, whereas specimens from four different sites were used for detection of
      C. trachomatis. Signs of friability and purulent endocervical discharge were
      documented at gynaecological examination. Specimens for microscopy were taken
      from the endocervix and urethra as well as the vaginal discharge, and bacterial
      vaginosis was examined for. The criteria being evaluated included cervical
      friability and/or pus; polymorphonuclear leukocytes (PMNL)/epithelium cell ratio
      in the vaginal discharge; and more than 30 PMNL per high-power field in the
      endocervical smear. The overall agreement of the indicators of cervicitis in
      women infected with C. trachomatis and/or M. genitalium was 40.5% (15/37), and
      for those women with negative tests 35.3% (12/34). The criteria for cervicitis
      require further evaluation, including study of a control group of women at low
      risk of having a sexually transmitted infection.

PMID- 20814630
TI  - Delusional parasitosis and the matchbox sign revisited: the international
      perspective.

PMID- 20814629
TI  - Hepatocellular carcinoma in variegate porphyria: a serious complication.
AB  - Variegate porphyria is an acute hepatic porphyria resulting from a partial
      deficiency of protoporphyrinogen oxidase, the penultimate enzyme in haem
      biosynthesis. Cutaneous symptoms and acute neurovisceral attacks are well-known
      clinical characteristics of the disease. Less studied, however, is the risk of
      developing hepatocellular carcinoma, an aggressive type of liver cancer. We
      describe here two Swiss patients with variegate porphyria and this serious
      complication. Common risk factors, including alcohol over-consumption or chronic
      hepatitis, were absent in both patients. Interestingly, one patient carried
      mutation 1082-1083insC in the PPOX gene, a prevalent sequence deviation in the
      Swiss variegate porphyria population, which was also found in a French patient
      with variegate porphyria and hepatocellular carcinoma. Recent studies indicate
      that individuals with acute hepatic porphyria have a 36- to 61-fold increased
      risk of manifesting hepatocellular carcinoma. The incidence rate ratio in the
      Swiss population was estimated to be 34, comparable with those found in the
      French and Finnish populations. Because this tumour is associated with a rising
      mortality, we suggest regular screening for hepatocellular carcinoma in all
      patients with variegate porphyria.

PMID- 20814631
TI  - Primary cutaneous aspergillosis.

PMID- 20814632
TI  - Valsartan-induced drug eruption followed by CD30+ pseudolymphomatous eruption.

PMID- 20814633
TI  - Oral alitretinoin in lichen planus: two case reports.

PMID- 20814634
TI  - CD8+ CD56+ mycosis fungoides with an indolent clinical behaviour: case report and
      literature review.

PMID- 20814635
TI  - Labial melanotic macule after application of topical tacrolimus: two case
      reports.

PMID- 20814636
TI  - Filaggrin null-mutations may be associated with a distinct subtype of atopic hand
      eczema.

PMID- 20814637
TI  - Development and progression of a periorbital sebaceous gland carcinoma in situ.

PMID- 20814638
TI  - SAPHO syndrome with unusual cutaneous manifestations treated successfully with
      etanercept.

PMID- 20814639
TI  - Cryosurgery during imiquimod cream treatment ("immunocryosurgery") for Bowen's
      disease of the skin: a case series.

PMID- 20814640
TI  - Tufted angioma associated with Kasabach-Merritt phenomenon: a therapeutic
      challenge.

PMID- 20814641
TI  - Lipoblastoma-like tumour of the lip in an adult woman.

PMID- 20814642
TI  - Squamous cell carcinoma in a chronic genital ulcer in Behcet's disease.

PMID- 20814643
TI  - A case of suppurative granuloma induced by insulin injection.

PMID- 20814644
TI  - Epstein-Barr virus-associated oral papulosis in graft-versus-host disease.

PMID- 20814645
TI  - Acute perniosis in elderly people: a predictive sign of systemic disease?

PMID- 20814646
TI  - Photosensitization induced by exposure to colour cathode ray tube monitor
      following topical 5-aminolaevulinic acid-based photodynamic therapy: a case
      report.

PMID- 20814647
TI  - Cutaneous presentation of mantle cell lymphoma.

PMID- 20814648
TI  - Toxic epidermal necrolysis induced by ofloxacin.

PMID- 20814649
TI  - Orificial tuberculosis in an immunocompetent careworker.

PMID- 20814650
TI  - Persistent shoe dermatitis caused by dimethyl fumarate.

PMID- 20814651
TI  - Asymptomatic brownish reticulate patch on the left thigh.

PMID- 20814652
TI  - A bluish pigmented cystic lesion of the nose.

PMID- 20814653
TI  - Multiple brownish macules on child's cheeks.

PMID- 20814654
TI  - Comparison of sequential left internal thoracic artery grafting and separate left
      internal thoracic artery and venous grafting : A 5-year follow-up.
AB  - OBJECTIVES: The superiority of left internal thoracic artery (LITA) grafting to
      the left anterior descending artery (LAD) is well established. Patency rates of
      80%-90% have been reported at 10-year follow-up. However, the superiority of
      sequential LITA grafting has not been proven. Our aim was to compare patency
      rates after sequential LITA grafting to a diagonal branch and the LAD with
      patency rates of LITA grafting to the LAD and separate vein grafting to a
      diagonal branch. METHODS: A total of 58 coronary artery bypass graft (CABG)
      patients, operated on between 01/2000 and 12/2002, underwent multi-slice computed
      tomography (MSCT) between 2006 and 2008. Of these patients, 29 had undergone
      sequential LITA grafting to a diagonal branch and to the LAD ("Sequential"
      Group), while in 29 the LAD and a diagonal branch were separately grafted with
      LITA and vein ("Separate" Group). Patencies of all anastomoses were investigated.
      RESULTS: Mean follow-up was 1958+/-208 days. The patency rate of the LAD
      anastomosis was 100% in the Sequential Group and 93% in the Separate Group
      (p=0.04). The patency rate of the diagonal branch anastomosis was 100% in the
      Sequential Group and 89% in the Separate Group (p=0.04). Mean intraoperative flow
      on LITA graft was not different between groups (69+/-8ml/min in the Sequential
      Group and 68+/-9ml/min in the Separate Group, p=n.s.). CONCLUSION: Patency rates
      of both the LAD and the diagonal branch anastomoses were higher after sequential
      arterial grafting compared with separate arterial and venous grafting at 5-year
      follow-up. This indicates that, with regard to the antero-lateral wall of the
      left ventricle, there is an advantage to sequential arterial grafting compared
      with separate arterial and venous grafting.

PMID- 20814655
TI  - [Analysis of mortality and convergence tendencies in inpatient care of stroke and
      myocardial infarction].
AB  - BACKGROUND: An increase in the convergence of medical services toward specialized
      hospitals with high case numbers as well as the effects on quality of care are
      often assumed to be the result of diagnosis-related groups (DRGs; case-based lump
      sum reimbursement). Estimates of the extent to which these effects occur in
      emergency diagnoses are not available. METHODS: Claims data relating to
      approximately 23.6 million insured within the period 2004-2007 (inclusive) were
      analyzed. All cases with the main diagnosis of stroke (ICD-10: I63 and I64) and
      myocardial infarction (ICD-10: I21) were included in the study. RESULTS:
      Increasing case numbers could be observed for all entities within the period
      studied (myocardial infarction: +12.71%; stroke: +1.73%). The absolute increase
      in case numbers seems to affect those hospitals with case numbers >100 per year,
      whereas case numbers of hospital groups including hospitals with low case numbers
      per year remain unchanged or grow slower. No absolute trend in mortality could be
      seen. However, a disproportionate rate of mortality in hospitals with low case
      numbers per year for both diagnoses was observed. CONCLUSION: The convergence of
      emergency treatment in a few specialized centers has not yet been accelerated by
      the implementation of DRGs. Essentially, relative changes can be seen due to case
      number increases in large centers rather than because of service cutbacks and
      shifts from smaller hospitals. The reason for this could be the need to maintain
      emergency care in rural regions, while specialized centers are increasingly built
      in urban areas.

PMID- 20814656
TI  - [Sexual dysfunction and its consequences in patients with cardiovascular
      diseases].
AB  - PURPOSE: Due to the high prevalence of sexual disorders in men and women with
      cardiovascular disease, the associations between sexual dysfunction, depression,
      anxiety, quality of life and partnership were investigated. Studies examining
      impairments to certain aspects of psychological health and interpersonal life in
      cardiac patients are still lacking. The SPARK (Sexuality of Patients in
      Rehabilitation of Cardiovascular Diseases) investigation is the first study which
      explores these relevant associations in German rehabilitation patients. METHODS:
      Five rehabilitation centers for cardiovascular diseases took part in our cross
      sectional study. Associations between sexual dysfunction and depression, anxiety,
      quality of life and partnership were tested using z-tests (resulting parameter
      prevalence rate ratio, PRR) and via multiple binary logistic regressions
      controlling for age and severity of cardiovascular disease as possible
      confounders (resulting parameter odds ratio, OR). RESULTS: Sexual function could
      be assessed in 261 men and 75 women (sexual activity during the previous month;
      for detailed flow chart see Fig. 1). In total, 43.1% of female patients reported
      a sexual dysfunction, while 20.2% of male patients stated to have at least
      moderate erectile dysfunction (ED). The proportion of self-assessed sexual
      problems is shown in Fig. 2. Women with a sexual dysfunction were impaired to a
      significantly higher extent compared to women without sexual dysfunction with
      regard to their quality of partnership (PRR 13.0; p=0.019; OR 25.42, confidence
      interval, CI, 2.5-254.9), anxiety (PRR 3.2; p=0.053; OR 4.43, CI 1.2-16.4) and
      psychological quality of life (PRR 2.4; p=0.115; OR 6.08, CI 1.6-22.9). Men with
      ED reported significantly stronger depression (PRR 3.6; p=0.003; OR 3.63, CI 1.5
      8.8) and anxiety (PRR 2.4; p=0.008; OR 2.88, CI 1.4-5.9) compared to men without
      ED. For detailed information see Tables 1 and 2. CONCLUSION: Due to the high
      proportion of men and women with cardiovascular disease reporting sexual
      disorders, depression and anxiety, screening for these disorders should be an
      integral part of comprehensive rehabilitation programs. In particular, the
      diagnosis and treatment of psychiatric comorbidity seem to be necessary from a
      tertiary preventive perspective.

PMID- 20814657
TI  - [Interventional, intramyocardial stem cell therapy in ischemic cardiomyopathy:
      update 2010].
AB  - BACKGROUND: The intracoronary application of autologous bone marrow cells has
      proven hitherto to be safe but not sufficiently effective in patients with
      ischemic cardiomyopathy. The interventional application of cells injected
      directly into the myocardium represents one possible approach to improve
      effectiveness. TECHNIQUES: The NOGA method is based on the CARTO technique, which
      has been evaluated extensively for safety and feasibility in patients with heart
      failure. In a first step, an electrically and anatomically exact map of the left
      ventricle is obtained. Guided by this three-dimensional map direct injection of
      the cells into the ischemic area can be easily performed. CLINICAL STUDIES: Since
      its introduction in 2002 many studies have proven the safety, feasibility and
      effectiveness of NOGA-guided regenerative therapy to the left ventricle. While
      several studies also suggest effectiveness regarding various parameters of left
      ventricular function, no larger multicenter study is available to date. Such
      studies with also clinical endpoints are currently ongoing. CONCLUSION: The
      currently available data support, but do not yet prove, the hypothesis that
      intramyocardial stem cell therapy using NOGA-guided injection into the myocardium
      is safe and feasible in both acute and chronic ischemic cardiomyopathy. Ongoing
      trials will reveal whether this approach will become the standard form for
      applying cell therapy to the heart.

PMID- 20814659
TI  - Brachial plexopathy after chemoradiotherapy for head and neck squamous cell
      carcinoma.
AB  - PURPOSE: To evaluate late brachial plexopathy after primary chemoradiotherapy for
      locally advanced head and neck squamous cell carcinoma. PATIENTS AND METHODS:
      Consecutive 43 disease-free patients were evaluated by a specifically developed
      26-item questionnaire. Retrospectively, the brachial plexus was delineated and
      the dose-volume histograms were calculated. RESULTS: After a median follow-up of
      24 months, no radiation-induced brachial plexopathy was reported in these 43
      patients. CONCLUSION: No radiation-induced brachial plexopathy was seen in the
      patient group, although 72.1% of the brachial plexuses received doses > 60 Gy.
      These findings should prompt further prospective studies and also stress the
      importance of trying to keep the doses to the brachial plexus as low as possible
      while covering the target volumes well.

PMID- 20814658
TI  - The use of FDG-PET to target tumors by radiotherapy.
AB  - Fluorodeoxyglucose positron emission tomography (FDG-PET) plays an increasingly
      important role in radiotherapy, beyond staging and selection of patients.
      Especially for non-small cell lung cancer, FDG-PET has, in the majority of the
      patients, led to the safe decrease of radiotherapy volumes, enabling radiation
      dose escalation and, experimentally, redistribution of radiation doses within the
      tumor. In limited-disease small cell lung cancer, the role of FDG-PET is
      emerging. For primary brain tumors, PET based on amino acid tracers is currently
      the best choice, including high-grade glioma. This is especially true for low
      grade gliomas, where most data are available for the use of (11)C-MET
      (methionine) in radiation treatment planning. For esophageal cancer, the main
      advantage of FDG-PET is the detection of otherwise unrecognized lymph node
      metastases. In Hodgkin's disease, FDG-PET is essential for involved-node
      irradiation and leads to decreased irradiation volumes while also decreasing
      geographic miss. FDG-PET's major role in the treatment of cervical cancer with
      radiation lies in the detection of para-aortic nodes that can be encompassed in
      radiation fields. Besides for staging purposes, FDG-PET is not recommended for
      routine radiotherapy delineation purposes. It should be emphasized that using PET
      is only safe when adhering to strictly standardized protocols.

PMID- 20814660
TI  - [TRT and psychotherapy in the treatment of tinnitus].
AB  - Basic requirements and results of tinnitus retraining therapy (TRT) as well as
      other habituation therapies with psychotherapeutic approaches in the treatment of
      tinnitus are examined closely in this literature review. In German-speaking
      countries experts generally aim for involvement of psychotherapists beyond the
      classic TRT developed by Jastreboff and Hazell. On the basis of a validated
      diagnostic test such as the Tinnitus Questionnaire according to Hiller and Goebel
      (1998), such a therapy regime is more effective than the "classic" procedure.
      Under different treatment approaches, cognitive behavioural therapy elements have
      been proven to be effective-even as a component of the TRT-as well as integrated
      variants in psychodynamic therapies. We have to give consideration to the fact
      that in all studies about the selection and inclusion criteria selective test
      conditions were established which suggest that in each case diverse patient
      groups were studied. In the overall picture it becomes apparent that depending on
      the severity of the tinnitus and accompanying hearing problems a dysfunction
      oriented and staged approach makes sense.

PMID- 20814661
TI  - Probing forces of menisci: what levels are safe for arthroscopic surgery.
AB  - PURPOSE: to facilitate effective learning, feedback on performance during
      arthroscopic training is essential. Less attention has been paid to feedback on
      monitoring safe handling of delicate tissues such as meniscus. The goal is to
      measure in vitro probing forces of menisci and compare them with a theoretical
      maximum probing force (TMPF). METHOD: menisci samples of ten cadavers were
      mounted on force platforms to measure probing forces up to 20 N in three
      directions. Nineteen subjects participated: six novices (experience <60
      arthroscopies), ten intermediates (>60 arthroscopies), and three faculty (>250 a
      year). All had to perform three tasks on each meniscus sample with an
      arthroscopic probe: push three times on the superior meniscal surface, perform
      one continuous run on the superior meniscal surface, and push three times on the
      inferior meniscal surface. The absolute maximum probing force (AMPF) was
      determined for each condition. A multivariable linear regression analysis was
      performed to assess the influence of experience on the force magnitude (P <
      0.05). AMPFs were compared to the TMPF (estimated to be 8.5 N). RESULTS: the AMPF
      of the push task was on average 2.8 N (standard deviation (SD) of 0.8 N), of the
      continuous run task 2.5 N (SD 0.9 N), and of the pull task 3.9 N (SD 2.0 N).
      Significant difference was present between experts and novices (P < 0.05). The
      AMPFs are in the same order of magnitude as the TMPF. CONCLUSION: the results
      indicate the necessity of using a safety level for tissue manipulation when
      training arthroscopy and a value for is magnitude.

PMID- 20814662
TI  - Double-bundle ACL reconstruction demonstrated superior clinical stability to
      single-bundle ACL reconstruction: a matched-pairs analysis of instrumented tests
      of tibial anterior translation and internal rotation laxity.
AB  - PURPOSE: To compare objective measures of in vivo joint laxity between patients
      treated with single-bundle (SB) or double-bundle (DB) anterior cruciate ligament
      (ACL) reconstructions. METHODS: Sixty-four patients matched by age, height,
      weight, and that had undergone unilateral SB or DB hamstring ACL reconstruction
      participated in this study. Bilateral anterior tibial translation (ATT) was
      recorded using the KT1000 arthrometer, and a robotic testing system was used to
      assess side-to-side differences in rotational characteristics. Each
      reconstruction was evaluated to determine how well it mimicked the
      anteroposterior (AP) and rotational biomechanics of the normal knee. A
      reconstruction was defined as mimicking the normal knee if ATT and internal
      rotation (IR) were within 3 mm and 3.5 degrees , respectively. RESULTS: Side-to
      side differences in ATT were significantly higher for the SB group (2.2 +/- 1.4
      mm) than the DB group (1.1 +/- 1.0 mm, P = 0.001). While relative side-to-side
      differences in IR did not differ between the SB (1.3 degrees ) and DB groups (1.1
      degrees , P = 0.82), absolute IR differences were significantly less with the DB
      reconstruction (2.1 degrees  vs. 4.7 degrees , P = 0.001). A significantly
      greater percentage of DB patients (81%, P = 0.0003) had both ATT and IR similar
      to the normal knee, compared to 34% of the SB patients; however, IKDC subjective
      scores did not differ between groups. Regardless of technique, patients with the
      greatest rotational laxity of their non-operative knee demonstrated significantly
      worse IKDC scores. CONCLUSION: DB reconstruction resulted in reduced side-to-side
      differences in both ATT and IR. The DB technique more consistently reproduced the
      biomechanical profile of the uninjured limb than did the SB technique without
      increasing the risk of over-constraining the knee.

PMID- 20814663
TI  - Anatomical placement of double femoral tunnels in anterior cruciate ligament
      reconstruction: anteromedial tunnel first or posterolateral tunnel first?
AB  - PURPOSE: The purpose of this study was to know which tunnel--the anteromedial
      (AM) bundle or the posterolateral (PL) bundle--should be prepared first to create
      the 2 femoral tunnels accurately in anatomic double-bundle (DB) anterior cruciate
      ligament (ACL) reconstruction. METHODS: Thirty-four patients were divided into 2
      groups of 17 depending on the sequence of preparation of the 2 femoral tunnels.
      In group A, the AM tunnel was prepared first, whereas the PL tunnel was prepared
      first in group P. ACL reconstruction was performed using a three-dimensional (3
      D) fluoroscopy-based navigation system to place the double femoral tunnels
      through an accessory medial portal. The double femoral socket positioning was
      evaluated by 3-D computed tomography (CT) scan image. RESULTS: The non-anatomical
      placement of the femoral sockets occurred in 5 patients (29%) in group A, whereas
      the 2 sockets were placed anatomically in all patients in group P (P < 0.05).
      Evaluation of the AM and the PL socket location on the 3-D CT images using the
      quadrant method showed more similar values to the laboratory data in a literature
      in group P than in group A. No complication occurred in group A, whereas
      complications such as socket communications or back wall blowout occurred in 5
      patients (29%) in group P (P < 0.05). CONCLUSION: The sequence of creating 2
      femoral tunnels through accessory medial portal affected the resultant location
      of the sockets and the rate of the complications. When femoral tunnels are
      prepared with a transportal technique, PL tunnel first technique seems to be
      superior to AM first technique regarding anatomic placement. However, PL tunnel
      first technique accompanies the risk of socket communication.

PMID- 20814664
TI  - Shed blood re-transfusion provides no benefit in computer-assisted primary total
      knee arthroplasty.
AB  - PURPOSE: This matched case-cohort retrospective study examined the effectiveness
      of shed blood re-transfusion in reducing the need for allogeneic blood
      transfusion in computer-assisted primary cemented total knee arthroplasty (TKA).
      METHODS: The shed blood re-transfusion system used was the cell saver system.
      Data from 146 cases were analyzed (73 patients with cell saver, 73 patients
      without cell saver). RESULTS: The ABT rate was similar in each group. The mean
      allogenic blood transfusion volume was similar for each group (CS=214+/-453 ml,
      non-CS=288+/-447 ml). The only factors correlated with allogenic blood
      transfusion use were low preoperative hemoglobin and low body mass index. Two
      patients in cell saver group experienced shivering after re-transfusion.
      CONCLUSION: Shed blood re-transfusion provided no blood management benefits in
      computer-assisted primary TKA and is therefore recommended only for selected
      patients with low hemoglobin levels and low body mass index.

PMID- 20814666
TI  - DNA sensor by using electrochemiluminescence of acridinium ester initiated by
      tripropylamine.
AB  - It was found that tripropylamine (TPA) could be used as a coreactant to initiate
      the electrochemiluminescence (ECL) of acridinium NHS ester (AE NHS) labels
      attached to DNA. The radicals generated in the electro-oxidation process of TPA
      reacted with AE NHS to form the excited N-methylacridone, giving rise to light
      emission. The AE/TPA ECL system was for the first time used as the detection
      system for developing an ECL-based DNA sensor. In the protocol, streptavidin
      modified gold nanoparticles were firstly immobilized onto a thiol-treated gold
      electrode. The streptavidin could specifically interact with the biontinylated
      capture DNA. Afterwards, the target DNA and the AE-labeled report DNA were
      conjugated onto the electrode step by step due to the hybridization reactions,
      and a sandwich-type sensor was fabricated. The ECL signals of the sensor were
      obtained under pulse potential condition in alkaline solution containing 50.0
      mmol L(-1) TPA. Under optimized experimental conditions, the linear range of the
      DNA sensor for the determination of the target DNA was from 5.0 * 10(-15) to 5.0
      * 10(-12) mol L(-1). The detection limit (S/N = 3) was 3.0 * 10(-15) mol L(-1).
      Moreover, the sensor could specifically recognize the target DNA against one base
      pair mismatched sequences, two base-pair mismatched sequences, and the
      noncomplementary sequences. It is of great application potential in clinic
      analysis.

PMID- 20814665
TI  - Evidence for an additional effect of whole-body vibration above resistive
      exercise alone in preventing bone loss during prolonged bed rest.
AB  - SUMMARY: The addition of whole-body vibration to high-load resistive exercise may
      provide a better stimulus for the reduction of bone loss during prolonged bed
      rest (spaceflight simulation) than high-load resistive exercise alone.
      INTRODUCTION: Prior work suggests that the addition of whole-body vibration to
      high-load resistive exercise (RVE) may be more effective in preventing bone loss
      in spaceflight and its simulation (bed rest) than resistive exercise alone (RE),
      though this hypothesis has not been tested in humans. METHODS: Twenty-four male
      subjects as part of the 2nd Berlin Bed Rest Study performed RVE (n = 7), RE (n =
      8) or no exercise (control, n = 9) during 60-day head-down tilt bed rest. Whole
      body, spine and total hip dual X-ray absorptiometry (DXA) measurements as well as
      peripheral quantitative computed tomography measurements of the tibia were
      conducted during bed rest and up to 90 days afterwards. RESULTS: A better
      retention of bone mass in RVE than RE was seen at the tibial diaphysis and
      proximal femur (p <= 0.024). Compared to control, RVE retained bone mass at the
      distal tibia and DXA leg sub-region (p <= 0.020), but with no significant
      difference to RE (p >= 0.10). RE impacted significantly (p = 0.038) on DXA leg
      sub-region bone mass only. Calf muscle size was impacted similarly by both RVE
      and RE. On lumbar spine DXA, whole-body DXA and calcium excretion measures, few
      differences between the groups were observed. CONCLUSIONS: Whilst further
      countermeasure optimisation is required, the results provide evidence that (1)
      combining whole-body vibration and high-load resistance exercise may be more
      efficient than high-load resistive exercise alone in preventing bone loss at some
      skeletal sites during and after prolonged bed rest and (2) the effects of
      exercise during bed rest impact upon bone recovery up to 3 months afterwards.

PMID- 20814667
TI  - NMR methods to monitor the enzymatic depolymerization of heparin.
AB  - Heparin and the related glycosaminoglycan, heparan sulfate, are polydisperse
      linear polysaccharides that mediate numerous biological processes due to their
      interaction with proteins. Because of the structural complexity and heterogeneity
      of heparin and heparan sulfate, digestion to produce smaller oligosaccharides is
      commonly performed prior to separation and analysis. Current techniques used to
      monitor the extent of heparin depolymerization include UV absorption to follow
      product formation and size exclusion or strong anion exchange chromatography to
      monitor the size distribution of the components in the digest solution. In this
      study, we used (1)H nuclear magnetic resonance (NMR) survey spectra and NMR
      diffusion experiments in conjunction with UV absorption measurements to monitor
      heparin depolymerization using the enzyme heparinase I. Diffusion NMR does not
      require the physical separation of the components in the reaction mixture and
      instead can be used to monitor the reaction solution directly in the NMR tube.
      Using diffusion NMR, the enzymatic reaction can be stopped at the desired time
      point, maximizing the abundance of larger oligosaccharides for protein-binding
      studies or completion of the reaction if the goal of the study is exhaustive
      digestion for characterization of the disaccharide composition. In this study,
      porcine intestinal mucosa heparin was depolymerized using the enzyme heparinase
      I. The unsaturated bond formed by enzymatic cleavage serves as a UV chromophore
      that can be used to monitor the progress of the depolymerization and for the
      detection and quantification of oligosaccharides in subsequent separations. The
      double bond also introduces a unique multiplet with peaks at 5.973, 5.981, 5.990,
      and 5.998 ppm in the (1)H-NMR spectrum downfield of the anomeric region. This
      multiplet is produced by the proton of the C-4 double bond of the non-reducing
      end uronic acid at the cleavage site. Changes in this resonance were used to
      monitor the progression of the enzymatic digestion and compared to the profile
      obtained from UV absorbance measurements. In addition, in situ NMR diffusion
      measurements were explored for their ability to profile the different-sized
      components generated over the course of the digestion.

PMID- 20814669
TI  - Automating a 96-well microtiter plate assay for identification of AGEs inhibitors
      or inducers: application to the screening of a small natural compounds library.
AB  - Advanced glycation end-products (AGEs) are involved in the pathogenesis of
      numerous affections such as diabetes and neurological diseases. AGEs are also
      implied in various changes in tissues and organs. Therefore, compounds able to
      break them or inhibit their formation may be considered as potential drugs,
      dietary supplements, or bioactive additives. In this study, we have developed a
      rapid and reliable (Z' factor calculation) anti-AGEs activity screening based on
      the overall fluorescence of AGEs. This method was successfully evaluated on known
      AGEs inhibitors and on a small library of natural compounds, yielding coherent
      results when compared with literature data.

PMID- 20814668
TI  - Analysis and characterization of heparin impurities.
AB  - This review discusses recent developments in analytical methods available for the
      sensitive separation, detection and structural characterization of heparin
      contaminants. The adulteration of raw heparin with oversulfated chondroitin
      sulfate (OSCS) in 2007-2008 spawned a global crisis resulting in extensive
      revisions to the pharmacopeia monographs on heparin and prompting the FDA to
      recommend the development of additional physicochemical methods for the analysis
      of heparin purity. The analytical chemistry community quickly responded to this
      challenge, developing a wide variety of innovative approaches, several of which
      are reported in this special issue. This review provides an overview of methods
      of heparin isolation and digestion, discusses known heparin contaminants,
      including OSCS, and summarizes recent publications on heparin impurity analysis
      using sensors, near-IR, Raman, and NMR spectroscopy, as well as electrophoretic
      and chromatographic separations.

PMID- 20814670
TI  - Evaluation of compressive strength index of the femoral neck in Caucasians and
      chinese.
AB  - Compressive strength index (CSI) of the femoral neck is a parameter that
      integrates the information of bone mineral density (BMD), femoral neck width
      (FNW), and body weight. CSI is considered to have the potential to improve the
      performance of assessment for hip fracture risk. However, studies on CSI have
      been rare. In particular, few studies have evaluated the performance of CSI, in
      comparison with BMD, FNW, and bending geometry, for assessment of hip fracture
      risk. We studied two large populations, including 1683 unrelated U.S. Caucasians
      and 2758 unrelated Chinese adults. For all the study subjects, CSI, femoral neck
      BMD (FN_BMD), FNW, and bending geometry (section modulus [Z]) of the samples were
      obtained from dual-energy X-ray absorptiometry scans. We investigated the age
      related trends of these bone phenotypes and potential sex and ethnic differences.
      We further evaluated the performance of these four phenotypes for assessment of
      hip fracture risk by logistic regression models. Chinese had significantly lower
      FN_BMD, FNW, and Z, but higher CSI than sex-matched Caucasians. Logistic
      regression analysis showed that higher CSI was significantly associated with
      lower risk of hip fracture, and the significance remained after adjusting for
      covariates of age, sex, and height. Each standard deviation (SD) increment in CSI
      was associated with odds ratios of 0.765 (95% confidence interval, 0.634, 0.992)
      and 0.724 (95% confidence interval, 0.569, 0.921) for hip fracture risk in
      Caucasians and Chinese, respectively. The higher CSI in Chinese may partially
      help explain the lower incidence of hip fractures in this population compared to
      Caucasians. Further studies in larger cohorts and/or longitudinal observations
      are necessary to confirm our findings.

PMID- 20814671
TI  - Role of vegetation in a constructed wetland on nutrient-pesticide mixture
      toxicity to Hyalella azteca.
AB  - The toxicity of a nutrient-pesticide mixture in nonvegetated and vegetated
      sections of a constructed wetland (882 m2 each) was assessed using Hyalella
      azteca 48-h aqueous whole-effluent toxicity bioassays. Both sections were amended
      with a mixture of sodium nitrate, triple superphosphate, diazinon, and permethrin
      simulating storm-event agricultural runoff. Aqueous samples were collected at
      inflow, middle, and outflow points within each section 5 h, 24 h, 72 h, 7 days,
      14 days, and 21 days postamendment. Nutrients and pesticides were detected
      throughout both wetland sections with concentrations longitudinally decreasing
      more in vegetated than nonvegetated section within 24 h. Survival effluent
      dilution point estimates-NOECs, LOECs, and LC50s-indicated greatest differences
      in toxicity between nonvegetated and vegetated sections at 5 h. Associations of
      nutrient and pesticide concentrations with NOECs indicated that earlier toxicity
      (5-72 h) was from permethrin and diazinon, whereas later toxicity (7-21 days) was
      primarily from diazinon. Nutrient-pesticide mixture concentration-response
      assessment using toxic unit models indicated that H. azteca toxicity was due
      primarily to the pesticides diazinon and permethrin. Results show that the
      effects of vegetation versus no vegetation on nutrient-pesticide mixture toxicity
      are not evident after 5 h and a 21-day retention time is necessary to improve H.
      azteca survival to >=90% in constructed wetlands of this size.

PMID- 20814672
TI  - Pulmonary metastases in children with osteosarcoma: characteristics and impact on
      patient survival.
AB  - BACKGROUND: Approximately 15-20% of patients with osteosarcoma present with
      detectable metastatic disease and the majority of whom (85%) have pulmonary
      lesions as the sole site of metastasis. Previous studies have shown that the
      overall survival rate among patients with localized osteosarcoma without
      metastatic disease is approximately 60-70% whereas survival rate reduces to 10
      30% in patients with metastatic disease. OBJECTIVE: To determine the incidence
      and characteristic features of pulmonary metastases in a group of osteosarcoma
      patients and correlate the findings with the prognostic outcome/survival.
      MATERIALS AND METHODS: Seventy-seven cases of histologically confirmed
      osteosarcoma were reviewed (47 male, 30 female, mean age 10.9). The site and size
      of the primary tumour and degrees of chemonecrosis were recorded. Lung metastases
      were analyzed according to their size, number, distribution and interval from
      diagnosis. The Kaplan-Meier method was used to analyze the survival probability
      curve. Significant differences (P < 0.05) were evaluated with the log-rank test
      for univariate analyses. RESULTS: Seventeen patients had synchronous and 11 had
      metachronous lung metastases. Sixteen (57%) underwent pulmonary metastasectomy.
      Nine of sixteen (56%) patients with metastasectomy and 10/12 (83%) patients
      without metastasectomy died. Poor chemonecrosis was associated with a worse
      outcome. Number, distribution and timing of lung metastases, but not the size of
      lung metastases, were of prognostic value for survival. CONCLUSION: Radiological
      detection of lung metastases is clinically important as it indicates a worse
      prognosis.

PMID- 20814673
TI  - Microbial 2,4,6-trinitrotoluene degradation: could we learn from (bio)chemistry
      for bioremediation and vice versa?
AB  - 2,4,6-Trinitrotoluene (TNT) is released in nature from manufacturing or
      demilitarization facilities but also after munitions firing/detonation or leakage
      from explosive remnants of war. Due to its toxicity and recalcitrance, life cycle
      of TNT-containing products and bioremediation are critical issues. As TNT is a
      strongly electron-deficient aromatic with a positive molecular quadrupole moment
      and three electrophilic nitro groups, its environmental fate is contingent upon
      specific sorptive electron donor-acceptor interactions and nucleophilic,
      reductive (bio)transformations. The microbial degradation of TNT is governed by
      cometabolism and therefore depends on the growth substrate(s) available in
      contaminated environments. Long considered an ecotoxicological safety endpoint,
      the immobilization of TNT metabolites derived from nitro moiety reduction in soil
      is controversial because they preferentially bind to the dissolved soil organic
      matter which can be released into surface and groundwaters. The ever-growing
      biochemical knowledge of TNT degradation has made bioaugmentation and
      phytoremediation attractive alternatives. While the discovery and engineering of
      microorganisms with novel/improved degradative abilities are very challenging,
      the deciphering of the physiological roles of promiscuous enzymes involved in TNT
      biodegradation, such as type II hydride transferases of the Old Yellow Enzyme
      family, opens new perspectives for bioremediation. Finally, transgenic plants
      have enabled effective phytoremediation at the field scale, which is emerging as
      the preferable in situ option to rehabilitate TNT-contaminated sites.

PMID- 20814674
TI  - Detection and quantification of remote microglial activation in rodent models of
      focal ischaemia using the TSPO radioligand CLINDE.
AB  - PURPOSE: Neuroinflammation is involved in stroke pathophysiology and might be
      imaged using radioligands targeting the 18 kDa translocator protein (TSPO).
      METHODS: We studied microglial reaction in brain areas remote from the primary
      lesion site in two rodent models of focal cerebral ischaemia (permanent or
      transient) using [125I]-CLINDE, a promising TSPO single photon emission computed
      tomography radioligand. RESULTS: In a mouse model of permanent middle cerebral
      artery occlusion (MCAO), ex vivo autoradiographic studies demonstrated, besides
      in the ischaemic territory, accumulation of [125I]-CLINDE in the ipsilateral
      thalamus with a binding that progressed up to 3 weeks after MCAO. [125I]-CLINDE
      binding markedly decreased in animals pre-injected with either unlabelled CLINDE
      or PK11195, while no change was observed with flumazenil pre-treatment,
      demonstrating TSPO specificity. In rats subjected to transient MCAO, [125I]
      CLINDE binding in the ipsilateral thalamus and substantia nigra pars reticulata
      (SNr) was significantly higher than that in contralateral tissue. Moreover,
      [125I]-CLINDE binding in the thalamus and SNr was quantitatively correlated to
      the ischaemic volume assessed by MRI in the cortex and striatum, respectively.
      CONCLUSION: Clinical consequences of secondary neuronal degeneration in stroke
      might be better treated thanks to the discrimination of neuronal processes using
      in vivo molecular imaging and potent TSPO radioligands like CLINDE to guide
      therapeutic interventions.

PMID- 20814675
TI  - In acute myeloid leukemia, B7-H1 (PD-L1) protection of blasts from cytotoxic T
      cells is induced by TLR ligands and interferon-gamma and can be reversed using
      MEK inhibitors.
AB  - B7-H1 (PD-L1) is a B7-related protein that inhibits T-cell responses. B7-H1
      participates in the immunoescape of cancer cells and is also involved in the long
      term persistence of leukemic cells in a mouse model of leukemia. B7-H1 can be
      constitutively expressed by cancer cells, but is also induced by various stimuli.
      Therefore, we examined the constitutive and inducible expression of B7-H1 and the
      consequences of this expression in human acute myeloid leukemia (AML). We
      analyzed B7-H1 expression in a cohort of 79 patients with AML. In addition, we
      studied blast cells after incubation with interferon-gamma or toll-like receptors
      (TLR) ligands. Finally, we evaluated functionality of cytotoxic T-cell activity
      against blast cells. Expression of B7-H1 upon diagnosis was high in 18% of
      patients. Expression of TLR2, 4 and 9 was detected in one-third of AML samples.
      Expression of TLR2 and TLR4 ligands or IFN-gamma induced by B7-H1 was found to
      protect AML cells from CTL-mediated lysis. Spontaneous B7-H1 expression was also
      found to be enhanced upon relapse in some patients. MEK inhibitors, including
      UO126 and AZD6244, reduced B7-H1 expression and restored CTL-mediated lysis of
      blast cells. In AML, B7-H1 expression by blasts represents a possible immune
      escape mechanism. The inducibility of B7-H1 expression by IFN-gamma or TLR
      ligands suggests that various stimuli, either produced during the immune response
      against leukemia cells or released by infectious microorganisms, could protect
      leukemic cells from T cells. The efficacy of MEK inhibitors against B7-H1
      mediated inhibition of CTLs suggests a possible cancer immunotherapy strategy
      using targeted drugs.

PMID- 20814676
TI  - Twenty-year results of the cementless Corail stem.
AB  - The concept of an extensive hydroxyapatite (HA) coating for the fixation of a
      tapered femoral stem (Corail(r)) was introduced 25 years ago in the hope that we
      could achieve durable biological fixation while preserving normal periprosthetic
      bone activity. The value of uncemented fixation using HA-coated implants is now
      widely admitted. However, the characteristics of implant coating and more
      specifically its extent still remain a subject of debate or even controversy.
      This prospective study conducted over a 20-year period has greatly contributed to
      demonstrating the reliability of the Corail(r) prosthesis, in terms of functional
      abilities, radiographic evidence and global survivorship. A full HA coating
      applied on a straight and proximally flared stem induces substantial short-, mid-
      and long-term benefits without any deleterious effects reported. Modifications of
      the bone pattern have been strictly limited: slight resorption at the calcar
      level, absence of cortical hypertrophy and alleged stress shielding. The
      radiological "silence" is one of the paramount facts clearly demonstrated.

PMID- 20814677
TI  - Applying the ecosystem approach to select priority areas for forest landscape
      restoration in the Yungas, Northwestern Argentina.
AB  - This paper proposes a method to select forest restoration priority areas
      consistently with the key principles of the Ecosystem Approach (EA) and the
      Forest Landscape Restoration (FLR) framework. The methodology is based on the
      principles shared by the two approaches: acting at ecosystem scale, involving
      stakeholders, and evaluating alternatives. It proposes the involvement of social
      actors which have a stake in forest management through multicriteria analysis
      sessions aimed at identifying the most suitable forest restoration intervention.
      The method was applied to a study area in the native forests of Northern
      Argentina (the Yungas). Stakeholders were asked to identify alternative
      restoration actions, i.e. potential areas implementing FLR. Ten alternative
      fincas-estates derived from the Spanish land tenure system-differing in relation
      to ownership, management, land use, land tenure, and size were evaluated. Twenty
      criteria were selected and classified into four groups: biophysical, social,
      economic and political. Finca Ledesma was the closest to the economic, social,
      environmental and political goals, according to the values and views of the
      actors involved in the decision. This study represented the first attempt to
      apply EA principles to forest restoration at landscape scale in the Yungas
      region. The benefits obtained by the application of the method were twofold: on
      one hand, researchers and local actors were forced to conceive the Yungas as a
      complex net of rights rather than as a sum of personal interests. On the other
      hand, the participatory multicriteria approach provided a structured process for
      collective decision-making in an area where it has never been implemented.

PMID- 20814678
TI  - Adhesion awareness: a national survey of surgeons.
AB  - BACKGROUND: Postoperative adhesions are the most frequent complication of
      abdominal surgery, leading to high morbidity, mortality, and costs. However, the
      problem seems to be neglected by surgeons for largely unknown reasons. METHODS: A
      survey assessing knowledge and personal opinion about the extent and impact of
      adhesions was sent to all Dutch surgeons and surgical trainees. The informed
      consent process and application of antiadhesive agents were questioned in
      addition. RESULTS: The response rate was 34.4%. Two thirds of all respondents
      (67.7%) agreed that adhesions exert a clinically relevant, negative effect. A
      negative perception of adhesions correlated with a positive attitude regarding
      adhesion prevention (rho = 0.182, p < 0.001). However, underestimation of the
      extent and impact of adhesions resulted in low knowledge scores (mean test score
      37.6%). Lower scores correlated with more uncertainty about indications for
      antiadhesive agents which, in turn, correlated with never having used any of
      these agents (rho = 0.140, p = 0.002; rho = 0.095, p = 0.035; respectively). Four
      in 10 respondents (40.9%) indicated that they never inform patients on adhesions
      and only 9.8% informed patients routinely. A majority of surgeons (55.9%) used
      antiadhesive agents in the past, but only a minority (13.4%) did in the previous
      year. Of trainees, 82.1% foresaw an increase in the use of antiadhesive agents
      compared to 64.5% of surgeons (p < 0.001). CONCLUSIONS: The magnitude of the
      problem of postoperative adhesions is underestimated and informed consent is
      provided inadequately by Dutch surgeons. Exerting adhesion prevention is related
      to the perception of and knowledge about adhesions.

PMID- 20814679
TI  - Reflections of the Hippocratic Oath in modern medicine.
AB  - Hippocratic Oath indicates a prevailing ethos rather than a professional
      approach, and it is still regarded as the cornerstone and foundation of the
      medical profession. Medicine in Ancient Greece was strongly influenced by the
      values of classical philosophy as introduced by its main representatives: Plato
      and Aristotle. Hippocrates himself has been recognized not only as a pioneering
      physician, but also as an outstanding philosopher. In his writings, he claimed
      that "the physician must insert wisdom in medicine" and denounced the
      technocratic aspect of the medical profession. The Hippocratic Oath constitutes a
      synopsis of the moral code of Ancient Greek medicine and contributes to the
      stabilization of the tri-part relationship among the physician, the patient, and
      the illness, as described by Hippocrates. The harmony of this interactive
      triangle has been deranged by several factors, such as technological evolution,
      public media, and cost-effective modalities with multiple consequences. In these
      terms, the reevaluation of the Hippocratic Oath and its time-enduring messages
      seems essential to reinstate the relationship between the physician and the
      patient under a new philosophico-medical prism.

PMID- 20814680
TI  - Pseudomonas seleniipraecipitatus sp. nov.: a selenite reducing gamma
      proteobacteria isolated from soil.
AB  - A Gram-negative, yellow pigmented bacterium designated strain CA5(T) that reduced
      selenite to elemental red selenium was isolated from soil. 16S rRNA gene sequence
      alignment identified the isolate as a novel Pseudomonas species with P.
      argentinensis, P. flavescens, and P. straminea as its closest relatives. Sequence
      alignments show that the 16S rRNA gene of strain CA5(T) differed from that of P.
      argentinensis, P. flavescens, and P. straminea by 1.3, 1.5, and 1.7%,
      respectively. The G+C content was 62.8 mol%, similar to the 62.7-63 mol% reported
      for P. flavescens but slightly higher than the 62.5-62.6 mol% of P. straminea and
      significantly higher than the 57.5-58.0 mol% of P. argentinensis. The major
      cellular fatty acids present in the CA5(T) strain were C18:1 omega7c (41.1%),
      C16:1 omega6c and C16:1 omega7c (25.7%), C16:1 (12.0%), C12:0 (8.0%), C12:0 3-OH
      (4.4%), and C10:0 3-OH (2.9%). The cellular fatty acid profile, GC content,
      phenotypic properties, and biochemical characteristics were consistent with its
      placement within the genus Pseudomonas. The name P. seleniipraecipitatus is
      proposed for these bacteria.

PMID- 20814681
TI  - Desulfovibrio legallis sp. nov.: a moderately halophilic, sulfate-reducing
      bacterium isolated from a wastewater digestor in Tunisia.
AB  - A new moderately halophilic sulfate-reducing bacterium (strain H1(T) ) was
      enriched and isolated from a wastewater digestor in Tunisia. Cells were curved,
      motile rods (2-3 x 0.5 MUm). Strain H1(T) grew at temperatures between 22 and 43
      degrees C (optimum 35 degrees C), and at pH between 5.0 and 9.2 (optimum 7.3
      7.5). Strain H1(T) required salt for growth (1-45 g of NaCl/l), with an optimum
      at 20-30 g/l. Sulfate, sulfite, thiosulfate, and elemental sulfur were used as
      terminal electron acceptors but not nitrate and nitrite. Strain H1(T) utilized
      lactate, pyruvate, succinate, fumarate, ethanol, and hydrogen (in the presence of
      acetate and CO2) as electron donors in the presence of sulfate as electron
      acceptor. The main end-products from lactate oxidation were acetate with H2 and
      CO2. The G + C content of the genomic DNA was 55%. The predominant fatty acids of
      strain H1(T) were C(15:0) iso (38.8%), C(16:0) (19%), and C(14:0) iso 3OH
      (12.2%), and menaquinone MK-6 was the major respiratory quinone. Phylogenetic
      analysis of the small-subunit (SSU) ribosomal RNA (rRNA) gene sequence indicated
      that strain H1(T) was affiliated to the genus Desulfovibrio. On the basis of SSU
      rRNA gene sequence comparisons and physiological characteristics, strain H1(T) is
      proposed to be assigned to a novel species of sulfate reducers of the genus
      Desulfovibrio, Desulfovibrio legallis sp. nov. (= DSM 19129(T) = CCUG 54389(T)).

PMID- 20814683
TI  - Simultaneous assessment of liver volume and whole liver fat content: a step
      towards one-stop shop preoperative MRI protocol.
AB  - OBJECTIVE: The purpose of this study was to evaluate the ability of a whole liver
      volume (WLV) segmentation algorithm to measure fat fraction (FF). METHODS: Twenty
      consecutive patients with histologically proven fatty liver disease underwent
      dual-echo in-phase/out-of-phase MRI and magnetic resonance spectroscopy (MRS) at
      1.5 T. Two readers independently performed semiautomatic 3D liver segmentation on
      the out-of-phase sequences using an active contour model. FF was calculated for
      voxels, segments and WLV. Segmentation inter-observer reproducibility was
      assessed by intra-class correlation coefficient (ICC) for WLV and FF. Fat
      fraction correlation and agreement as determined by histology, MRS and MRI were
      determined. RESULTS: ICC was 0.999 (95% CI: 0.999-1, P < 0.001) for WLV FF
      calculation and 0.996 (95% CI: 0.990-0.998, P < 0.001) for whole liver volume
      calculations. Strong correlations were found between FF measured by histology,
      MRS and WLV-MRI. A Bland-Altman analysis showed a good agreement between FF
      measured by MRS and WLV-MRI. No systematic variations of FF was found between
      segments when analyzed by ANOVA (F = 1.78, P = 0.096). CONCLUSION: This study
      shows that a reproducible whole liver volume segmentation method to measure fat
      fraction can be performed. This strategy may be integrated to a "one-stop shop"
      protocol in liver surgery planning.

PMID- 20814684
TI  - [Canaloplasty. A new way in glaucoma surgery?].
AB  - Evaluation of the surgical treatment of open angle glaucoma depends on values,
      such as target pressure, success rates and complication rates. Canaloplasty is a
      new non-penetrating method for glaucoma surgery and the aim of this article is to
      present the surgical approach, indications, results and post-operative therapy.
      During the operation a viscocanalostomy according to Robert Stegmann is
      performed. Subsequently a microcatheter with an outer diameter of 200 MU is used
      to circumferentially dilate Schlemm's canal. During the dilation microvolumes of
      a high viscosity ophthalmic viscosurgical device (OVD) (sodium hyaluronate) are
      injected. After successful dilation the catheter is retracted and at the same
      time a 10.0 Prolene suture is placed in the canal and closed tightly to apply
      permanent tension to the trabecular meshwork.

PMID- 20814685
TI  - Mechanistic characterization of gastric copper transport in rainbow trout.
AB  - An in vitro gut-sac technique and (64)Cu as a radiotracer were used to
      characterize gastric copper (Cu) transport. Cu transport was stimulated by low
      luminal pH (4.0 vs. 7.4), to a greater extent than explained by the increased
      availability of the free Cu(2+) ion. At pH = 4.0, uptake kinetics were indicative
      of a low affinity (K (m) = 525 MUmol L(-1)), saturable carrier-mediated component
      superimposed on a large linear (diffusive and/or convective) component, with
      about 50% occurring by each pathway at Cu = 50 MUmol L(-1). Osmotic gradient
      experiments showed that solvent drag via fluid transport may play a role in Cu
      uptake via the stomach, in contrast to the intestine. Also unlike the intestine,
      neither the Na(+) gradient, high Ag, nor phenamil had any influence on gastric Cu
      transport, and a tenfold excess of Fe and Zn failed to inhibit Cu uptake. These
      findings indicate that neither Na(+)-dependent pathways nor DMT1 are likely
      candidates for carrier-mediated Cu transport in the stomach. We have cloned a
      partial cDNA sequence for the copper transporter Ctr1, and show its mRNA
      expression in all segments of the trout gastrointestinal tract, including the
      stomach. Based on the fact that this transporter is functional at low pH
      conventionally found in the stomach lumen, we suggest Ctr1 is a pathway for
      gastric Cu transport in trout. Extreme hypoxia inhibited Cu uptake. High P(CO2)
      levels (7.5 torr) increased Cu uptake and acetazolamide (100 MUmol L(-1))
      significantly inhibited Cu uptake, indicating carbonic anhydrase activity was
      involved in gastric Cu transport. Transport of Cu was insensitive to bafilomycin
      (10 MUmol L(-1)) suggesting a V-ATPase did not play a direct role in the process.
      Expression (mRNA) of H (+) , K (+)-ATPase, carbonic anhydrase 2, and the alpha-3
      isoform of Na (+)-K (+)-ATPase were observed in the stomach. We suggest these
      enzymes facilitate Cu transport in the stomach indirectly as part of a
      physiological mechanism exporting H(+) to the cell exterior. However, pre
      treatment with the H (+) , K (+)-ATPase proton pump blocker omeprazole did not
      affect gastric Cu transport, suggesting that other mechanisms must also be
      involved.

PMID- 20814686
TI  - Influence of pregnancy and smoking on brachial artery flow-mediated dilation
      values and time until maximum response.
AB  - PURPOSE: To evaluate the effect of pregnancy and smoking on endothelial function
      using brachial artery flow-mediated dilation (FMD) and to determine the time
      necessary until the occurrence of maximum brachial artery dilation after
      stimulus. METHODS: This study was an observational study evaluating 133 women,
      who were grouped as follows: non-smoking pregnant women (N = 47), smoking
      pregnant women (N = 33), non-smoking women (N = 34), and smoking pregnant women
      (N = 19). The diameter of the brachial artery was measured at baseline and at 30,
      60, 90 and 120 s after stimulus. The relative change of brachial artery was
      determined for each of these four moments. FMD measured at 60 s after stimulus
      was compared between the groups. RESULTS: The maximum FMD was observed at 60 s
      after cuff release in all groups. FMD was greater among non-smoking pregnant
      women compared to smoking pregnant women (11.50 +/- 5.77 vs. 8.74 +/- 4.83; p =
      0.03) and also between non-smoking non-pregnant women compared to smoking non
      pregnant women (10.52 +/- 4.76 vs. 7.21 +/- 5.57; p = 0.03). CONCLUSIONS: Maximum
      FMD was observed approximately 60 s after stimulus in all groups regardless of
      smoking and pregnancy status. The smoking habit seems to lead to endothelial
      dysfunction both in pregnant and non-pregnant women, as demonstrated by the lower
      FMD in smokers.

PMID- 20814687
TI  - Antibiotic chemotherapy during pregnancy and lactation period: aspects for
      consideration.
AB  - BACKGROUND: Infections during gestation, delivery and the postnatal period can
      jeopardise not only the mother, but also the child. Along with chromosomal
      abnormalities and immunological diseases, infection in early pregnancy represents
      the most important reason for abortion. During the second and third trimester,
      infections are the principal cause for preterm labour, premature membrane
      rupture, premature delivery and the resultant complications in the newborn child.
      Many pregnant women are very cautious about taking antibiotics due to primarily
      potentially detrimental effects on the unborn child. However, there are no
      contraindications for antibiotic treatment during pregnancy in the event of a
      serious infectious disease of the mother. MATERIALS AND METHODS: In this review
      the indications and contraindications of the administration of antibiotics during
      pregnancy are being reviewed. RESULTS: Penicillins are a first-line antibiotic
      treatment during pregnancy, with the exception of cases in which there is a
      maternal allergy to penicillin. Cephalosporins are another first-line antibiotic
      used during pregnancy. In principle, more commonly used cephalosporins should be
      given priority. Owing to associated nephrotoxicity and ototoxicity,
      aminoglycosides should not be prescribed at any time during pregnancy. Systematic
      use of aminoglycosides should be considered solely in the event of life
      threatening infections with gram-negative pathogens and/or treatment failure of
      recommended antibiotics during pregnancy. The use of metronidazole is also
      permitted during pregnancy, provided the indications for its use have been
      strictly verified. Lincosamides should be used only if penicillins,
      cephalosporins and erythromycin have failed to eradicate infection. Sulfonamides,
      trimethoprim and cotrimoxazole are second-line agents for the use during
      pregnancy. Tetracyclines should not be administered to pregnant women after the
      fifth week of pregnancy, and are deemed contraindicated. As a precautionary
      measure, gyrase inhibitors are also contraindicated for pregnant women, children
      and young adolescents. CONCLUSION: On the basis of our current state of
      knowledge, the vast majority of antibiotics do not cause serious harm to the
      unborn child if used properly and at the appropriate doses during pregnancy. The
      treatment with an antibiotic that is contraindicated does not justify termination
      of pregnancy. However, ultimately no medicine, including antibiotics, can be
      described as absolutely safe.

PMID- 20814688
TI  - Reactive oxygen species measurement in neat and washed semen: comparative
      analysis and its significance in male infertility assessment.
AB  - PURPOSE: Oxidative stress (OS) is a major concern in idiopathic male infertility
      as elevated levels of reactive oxygen species (ROS) in the semen is believed to
      adversely affect sperm functional competence and damage both nuclear and
      mitochondrial DNA. Therefore, identifying infertile men with seminal OS may be
      used as a valuable tool in the assessment of male infertility. Semen is a complex
      mixture of spermatozoa and seminal plasma which is rich in enzymatic and non
      enzymatic antioxidants. However, the measurement of ROS in the semen and its
      application in male infertility assessment is poorly understood. METHODS: The aim
      of the present study was to compare the significance of ROS measurement in washed
      and neat semen. The study included 65 infertile men with abnormal semen (SA)
      parameters, 17 infertile men with normal semen (NS) parameters and 43 fertile
      controls (FC). ROS levels in both washed and neat semen were measured by luminol
      dependent chemiluminescence assay and the values were expressed as 10(4 )RLU per
      minute per 20 million spermatozoa. RESULTS: The levels of ROS in both washed and
      neat semen were found to be significantly higher (P < 0.0001) in infertile men
      with abnormal and normal semen parameters as compared with FC (P < 0.0001). The
      lowest median level of ROS was found in FC (neat semen 0.03, washed semen 0.24),
      whereas infertile men with SA group had the highest median ROS level (neat semen
      3.44, washed semen 27.42). In all subjects, ROS levels were found to be higher in
      washed semen than in neat semen. A strong positive correlation (r = 0.847, P <
      0.0001) of ROS levels between neat and washed semen was observed. CONCLUSION:
      Measurement of ROS in neat semen reflects the original oxidative status in the
      actual sperm microenvironment and is an easy, simple, inexpensive and rapid
      method compared with ROS measurement from washed semen. ROS measurement in washed
      semen is done to assess ROS levels following sperm processing as in cases opting
      for assisted conception. As both ROS values in neat and washed show a positive
      correlation, neat semen may be used as a valuable tool for identifying infertile
      men with seminal OS. ROS levels are elevated in nearly 70% men with idiopathic
      infertility. Hence, ROS analysis in neat semen has both good diagnostic and
      prognostic value in male infertility assessment.

PMID- 20814689
TI  - Endonasal phototherapy significantly alleviates symptoms of allergic rhinitis,
      but has a limited impact on the nasal mucosal immune cells.
AB  - The literature documents the fact that UV irradiation of cutaneous Langerhans
      cells (LC) in vivo prevents the development of contact allergy and produces long
      lasting immunosuppression. However, not much is known about the effect of UV
      irradiation on the LC of the nasal mucosa and their connection with clinical
      scores. Local antigen presentation may be necessary for both primary and recall T
      cell responses to birch pollen in patients with hay fever. Endonasal phototherapy
      combination of UVB (5%), UVA (25%) and visible light (70%) utilises the
      immunosuppressive effects of UV irradiation. The aim of this study was to
      correlate clinical symptom scores with possible changes in the LC of the nasal
      mucosa induced by UV radiation. The clinical effectiveness of this form of
      treatment is discussed. Nasal biopsies were obtained from ten birch pollen
      sensitive patients with seasonal rhinitis before and after endonasal
      phototherapy. All patients showed a significant clinical benefit post-treatment
      as assessed by standardised instruments, including total nasal symptom score,
      nasal congestion score, nasal itching score, sneezing score, nasal secretion
      score and impairment-to-health score. However, we found no significant
      morphological changes, to, or quantitative differences in, the CD1a+, CD4, CD8 or
      CD31 cells before and 14 days after treatment. Despite the positive clinical
      effect, the study revealed no effect of UV irradiation on the LC and other
      analysed cells of the nasal mucosa immune system. Possible reasons for this are
      discussed.

PMID- 20814690
TI  - Role of 18F-FDG PET in detecting primary site in the patient with primary unknown
      carcinoma.
AB  - The aim of this study was to verify the effectiveness of positron emission
      tomography (PET) in detecting primary sites in carcinoma of unknown primary (CUP)
      patients. In this study, CUP represented a group of heterogeneous tumors that
      shared the clinical manifestation of metastatic carcinoma with no obvious primary
      site at the time of first diagnosis, which included clinical investigations,
      computed tomography, magnetic resonance imaging and panendoscopy. We reviewed the
      records of 24 patients with CUP between January 1995 and December 2009. The
      patients who demonstrated additional tracer uptake sites other than previously
      known metastatic lesions by PET scan were done direct biopsies for the sites of
      accumulation. Patients who had a negative PET scan or for whom the primary site
      could not be identified by direct biopsies underwent examination under anesthesia
      of the at-risk occult tumor sites. PET scan demonstrated focal accumulation
      suspicious for primary tumor in 12 (50.0%) of 24 patients: tonsil 5, nasopharynx
      3, hypopharynx 1, tongue 1, larynx 1, and maxillary sinus 1. A subsequent biopsy
      of these sites revealed primary cancer in 9 (37.5%) of 24 patients: tonsil 5,
      nasopharynx 1, hypopharynx 1, tongue 1, and maxillary sinus 1. In the remaining
      three patients, no malignant cells were found by the biopsy of the accumulated
      area: nasopharynx 2, larynx 1. PET scans increase the yield of primary tumor by
      37.5%. The sensitivity, specificity for PET scan were 80.8, 76.9%, respectively.
      PET scanning is useful in detecting primary cancer of CUP patients.

PMID- 20814691
TI  - Sex discrimination from the glenoid cavity in black South Africans: morphometric
      analysis of digital photographs.
AB  - Given that skeletal material recovered from medicolegal contexts is often
      incomplete or damaged, forensic anthropologists need to have a variety of
      techniques at their disposal in order to correctly determine the sex of
      unidentified human remains. The purpose of the present study, therefore, was to
      produce practical standards for discriminating the sex of black South Africans
      using measurements of the glenoid cavity of the scapula. Standardized digital
      photographs of the left glenoid fossa were taken for 60 males and 60 females
      drawn from the Pretoria Bone Collection. An image analysis software program was
      then used to collect height, breadth, area, and perimeter data from each digital
      photograph. All four dimensions of the glenoid cavity were highly sexually
      dimorphic in this population group (p < 0.0001). Univariate logistic regression
      analysis yielded overall sex prediction success rates ranging from 88.3% for area
      of the glenoid fossa to 85.8% for glenoid fossa breadth. Multivariate procedures
      did not provide increased accuracy over those using only a single variable.
      Classification sex biases were below 5.0% for all equations. These results
      demonstrate that the analysis of glenoid cavity size provides a highly accurate
      method for discriminating the sex of black South Africans.

PMID- 20814692
TI  - Similarity and match rates of the human dentition in three dimensions: relevance
      to bitemark analysis.
AB  - Uniqueness of the human dentition is a fundamental premise in bitemark analysis.
      Despite the importance of this key aspect of bitemark methodology, systematic
      studies of large populations have been limited. Furthermore, there have been no
      investigations of the significance of the third dimension with regard to dental
      uniqueness. One hundred digitally scanned mandibular models were analyzed in both
      2D and three dimension (3D) using Landmark software. Additionally, 500 3D
      maxillary and mandibular sets were investigated for determining dental match
      rate. Statistical analysis was performed with geometric morphometric methods.
      Results show that measurements in 3D preserve more information about the
      dentition, reducing but not eliminating random matches in a sample population of
      100 mandibular dentitions. Examination of pairs of maxillary and mandibular
      dentitions showed a substantial number of random matches (197 maxillary, 51
      mandibular, one of both maxillary and mandibular). Conclusions indicate that a
      zero match rate cannot be claimed for the population studied.

PMID- 20814693
TI  - Positional nystagmus reversing from geotropic to apogeotropic: a new central
      vestibular syndrome.

PMID- 20814694
TI  - Determination of absolute size of fundus objects.
AB  - BACKGROUND: Creating multiple beam interference fringes on the retina using the
      "retina fringe projector" (RFP) provides us with a scale which can be used to
      determine the absolute size of objects at the fundus. METHODS: The procedure is
      tested on an model eye, the optical parameters of which are varied in order to
      simulate different refraction conditions. The RFP was used to determine the size
      of a known object at the model fundus; the result was then checked against the
      real value of the object. In a second series of measurements, the RFP fringes
      were included in fundus photos of 52 patients with varying levels of ametropia,
      taken at the University Eye Clinic in Jena using the FF450 fundus camera
      (manufacturer: Carl Zeiss Meditec AG) for diagnostic purposes. The distance
      between the fringes was determined using both the RFP and the Littmann method.
      RESULTS: The differences to the real value of the fundus size of a known object
      deviated on average by 1 to 2%, and always remained under 3% in the model eye. A
      very good correlation between RFP and Littmann methods results could be found in
      the clinical part of the study. The resulting deviations are below 2.5%.
      CONCLUSION: Integration of a RFP in a fundus camera permits measurement of
      absolute values of the retina, regardless of the type of observation or
      documentation. Knowing the real size of fundus objects holds a potential in many
      clinical classification scales of fundus objects such as drusen or vessels, or in
      optimizing photodynamic therapy spot size measurement.

PMID- 20814695
TI  - Long-term follow-up of a supradescemetic keratoprosthesis in rabbits: an
      immunofluorescence study.
AB  - OBJECTIVE: To evaluate the long-term clinical and immunohistological outcome of
      two different non-penetrating keratoprosthesis (KPro) implanted in non-injured
      rabbit corneas. MATERIALS AND METHODS: Three rabbits underwent implantation of a
      pHEMA-MMA(34) synthetic cornea in the supradescemetic space, and PMMA synthetic
      corneas in the supradescemetic space and within the central stroma. Animals were
      followed for at least 24 months before euthanasia. Periodic evaluation was
      performed with slit-lamp examination and photography. At the end of the follow
      up, histological examination including hematoxylin eosin staining and
      immunocharacterization against collagen IV, alpha smooth muscle actin (alpha-SMA)
      and macrophages was performed. RESULTS: The pHEMA-MMA(34) implant was not
      extruded, and remained transparent until the end of follow-up. This material did
      not induce any cell infiltration, corneal scarring or tissue remodeling in the
      surrounding stroma as shown by immunofluorescence. In contrast, synthetic corneas
      made of PMMA-induced myofibroblast differentiation, stromal remodeling and
      macrophage infiltration. This reaction was even more significant in the rabbit
      with the PMMA implant within the corneal stroma. CONCLUSION: pHEMA-MMA(34) was
      clinically biocompatible, and did not induce any inflammatory reaction or
      scarring when implanted in the supradescemetic space. This material showed more
      promising biocompatibility results than for PMMA, whether implanted within the
      central cornea stroma or in the supradescemetic space.

PMID- 20814696
TI  - Transcutaneous bilirubin nomogram for predicting neonatal hyperbilirubinemia in
      healthy term and late-preterm Chinese infants.
AB  - Identifying infants that will develop significant hyperbilirubinemia with the
      risk of kernicterus, and planning appropriate follow-up strategies, is
      particularly challenging. In this study, 36,921 transcutaneous bilirubin (TcB)
      measurements were obtained from 6,035 healthy neonates (gestational age >= 35
      weeks and birth weight >= 2,000 g) between January 1 and December 31, 2009. All
      measurements were performed with the JM-103 bilirubinometer at designated times
      between 0 and 168 postnatal hours. TcB percentiles were calculated and used to
      develop an hour-specific nomogram. The rate of increase in TcB was higher during
      the first 72 h of age, after which levels declined to a plateau by 72-108 h of
      age. We constructed a TcB nomogram by using the 40th, 75th, and 95th percentile
      values of TcB for every 12 h of the studied interval. The 75th percentile curve
      of the nomogram may be an ideal cutoff point for intensive follow-up of the
      neonate for hyperbilirubinemia as it carries very high sensitivity (78.7%) and
      negative predictive value (98.5%). The specificity (45.7%) and positive
      predictive value (15.5%) decreased to reach their lowest levels at the 40th
      percentile. Of the neonates in the high-risk zone, 167 (48.8%) infants had
      persistent subsequent hyperbilirubinemia post-discharge, compared with 292
      (27.0%) infants in the high-intermediate-risk zone at discharge. One-hundred and
      seventeen (5.5%) infants in the low-intermediate-risk zone moved into the high
      risk zone during follow-up. No newborn infants in the low-risk zone became high
      risk during follow-up. We provide an hour-specific TcB nomogram to predict
      neonatal hyperbilirubinemia in healthy term and late-preterm Chinese infants.

PMID- 20814697
TI  - Individual and social predictors of screen-viewing among Spanish school children.
AB  - Many children exceed suggested screen-viewing guidelines and this is likely to be
      a risk factor for obesity. Understanding the predictors of screen-viewing may be
      the first step in designing interventions that target these behaviours, but there
      is lack of information on predictors among Spanish children. This study examined
      associations between individual, friend and family based social variables and
      screen-viewing behaviours, and how these associations differ by age and gender in
      a sample of Spanish children. Participants were 247 primary school-aged and 256
      secondary school-aged children and their parents. Children reported time spent in
      screen-viewing and information about individual and friend and family based
      social variables. Body mass index was assessed and children were classified using
      International Obesity Task Force cut-off points. Parents reported
      sociodemographic characteristics and family co-viewing practices. Lower self
      efficacy for reducing screen-viewing (console playing p < 0.05; overall p <
      0.01), stronger sedentary group-norms (TV p < 0.001; console playing p < 0.05;
      overall p < 0.05) and stronger social reasons (console playing p < 0.05) were
      associated with higher screen-viewing. For younger children, parental screen
      viewing rules appeared to be significant predictors while family co-viewing
      practices were significant predictors for older children. Older children (TV p <
      0.001; console playing p < 0.01; overall p < 0.001) and males (TV p < 0.01;
      console playing p < 0.001; overall p < 0.01) were likely to spend more time
      screen-viewing. Individual and social factors influence children's screen-viewing
      and operate differently during childhood. Increasing self-efficacy may be
      important for screen-viewing based behaviour changes. Friends and parents play a
      central role, therefore understanding the dynamics of friends and targeting
      family influences may be critical to the success of interventions to reduce
      screen-viewing.

PMID- 20814698
TI  - Induced changes in island fox (Urocyon littoralis) activity do not mitigate the
      extinction threat posed by a novel predator.
AB  - Prey response to novel predators influences the impacts on prey populations of
      introduced predators, bio-control efforts, and predator range expansion.
      Predicting the impacts of novel predators on native prey requires an
      understanding of both predator avoidance strategies and their potential to reduce
      predation risk. We examine the response of island foxes (Urocyon littoralis) to
      invasion by golden eagles (Aquila chrysaetos). Foxes reduced daytime activity and
      increased night time activity relative to eagle-naive foxes. Individual foxes
      reverted toward diurnal tendencies following eagle removal efforts. We quantified
      the potential population impact of reduced diurnality by modeling island fox
      population dynamics. Our model predicted an annual population decline similar to
      what was observed following golden eagle invasion and predicted that the observed
      11% reduction in daytime activity would not reduce predation risk sufficiently to
      reduce extinction risk. The limited effect of this behaviorally plastic predator
      avoidance strategy highlights the importance of linking behavioral change to
      population dynamics for predicting the impact of novel predators on resident prey
      populations.

PMID- 20814699
TI  - On the causes of variability in amounts of airborne grass pollen in Melbourne,
      Australia.
AB  - In Melbourne, Australia, airborne grass pollen is the predominant cause of hay
      fever (seasonal rhinitis) during late spring and early summer, with levels of
      airborne grass pollen also influencing hospital admissions for asthma. In order
      to improve predictions of conditions that are potentially hazardous to
      susceptible individuals, we have sought to better understand the causes of
      diurnal, intra-seasonal and inter-seasonal variability of atmospheric grass
      pollen concentrations (APC) by analysing grass pollen count data for Melbourne
      for 16 grass pollen seasons from 1991 to 2008 (except 1994 and 1995). Some of
      notable features identified in this analysis were that on days when either
      extreme (>100 pollen grains m(-3)) or high (50-100 pollen grains m(-3)) levels of
      grass pollen were recorded the winds were of continental origin. In contrast, on
      days with a low (<20 pollen grains m(-3)) concentration of grass pollen, winds
      were of maritime origin. On extreme and high grass pollen days, a peak in APC
      occurred on average around 1730 hours, probably due to a reduction in surface
      boundary layer turbulence. The sum of daily APC for each grass pollen season was
      highly correlated (r = 0.79) with spring rainfall in Melbourne for that year,
      with about 60% of a declining linear trend across the study period being
      attributable to a reduction of meat cattle and sheep (and hence grazing land) in
      rural areas around Melbourne. Finally, all of the ten extreme pollen events (3
      days or more with APC > 100 pollen grains m(-3)) during the study period were
      characterised by an average downward vertical wind anomaly in the surface
      boundary layer over Melbourne. Together these findings form a basis for a fine
      resolution atmospheric general circulation model for grass pollen in Melbourne's
      air that can be used to predict daily (and hourly) APC. This information will be
      useful to those sectors of Melbourne's population that suffer from allergic
      problems.

PMID- 20814700
TI  - Development of the Psychosocial Distress Questionnaire-Breast Cancer (PDQ-BC): a
      breast cancer-specific screening instrument for psychosocial problems.
AB  - PURPOSE: The aim of the present study was to develop a short, easy-to-use, and
      acceptable psychosocial screening instrument specific for breast cancer patients.
      METHODS: Before the start of adjuvant chemotherapy, 164 (98.8%) women completed
      the Psychosocial Distress Questionnaire-Breast Cancer (PDQ-BC) as part of routine
      care. The PDQ-BC consists of questions about psychological risk factors (i.e.,
      trait anxiety and (lack of) social support), psychosocial problems (i.e., state
      anxiety and depressive symptoms), social problems, physical problems, body image,
      financial problems, sexual problems, clinical factors (type of surgery, adjuvant
      treatment other than chemotherapy and psychiatric morbidity), and demographic
      factors (marital status, age, and age of children). RESULTS: On average, patients
      indicated that they needed 5 min to complete the PDQ-BC. All subscales were
      significantly correlated with each other, except the correlations of social
      support with physical problems and body image. Confirmatory factor analysis
      supported the internal structure of the PDQ-BC (comparative fit index = 0.95
      (chi(2)(24) = 43.3), p = 0.009; non-normed fit index = 0.91; root mean square
      error of approximation = 0.073). The internal consistency (Cronbach's alphas) of
      the subscales trait anxiety, state anxiety, depressive symptoms, body image,
      social problems, and physical problems were 0.88, 0.85, 0.86, 0.79, 0.42, and
      0.69, respectively. CONCLUSION: The PDQ-BC is an easy-to-complete, acceptable,
      non-burdensome, and short screening instrument for routine use in breast cancer
      patient care. This instrument facilitates a greater awareness of the concerns and
      needs for breast cancer patients care during treatment with chemotherapy and the
      follow-up. It is linked to a good referral system to guide allocation to the
      different levels of psychosocial care providers.

PMID- 20814701
TI  - Diagnostic procedures for IgG4-related sclerosing cholangitis.
AB  - BACKGROUND/PURPOSE: IgG4-related sclerosing cholangitis (IgG4-SC) is one of
      several diseases associated with autoimmune pancreatitis (AIP). However, diffuse
      cholangraphic abnormalities seen in association with AIP may resemble those seen
      in primary sclerosing cholangitis (PSC), and the presence of segmental stenosis
      suggests cholangiocarcinoma. IgG4-SC responds well to steroid therapy, whereas in
      contrast, liver transplantation is the only effective therapy for PSC, and
      surgical intervention is also needed for cholangiocarcinoma. The aim of this
      review was to establish the diagnostic procedures for IgG4-SC. METHODS: A
      literature search was conducted, covering English-language articles dealing with
      IgG4-SC published between 1991 and March 2010. As clinical data on IgG4-SC are
      limited, the author also took into consideration his own clinical experience with
      the treatment of IgG4-SC over a period of more than 19 years. RESULTS: When
      intrapancreatic stenosis is detected, pancreatic cancer should be ruled out. If
      multiple intrahepatic stenosis is evident, PSC should be discriminated on the
      basis of cholangiographic findings and liver biopsy with IgG4 immunostaining. An
      association with inflammatory bowel disease (IBD) is suggestive of PSC. If
      stenosis is demonstrated in the hepatic hilar region, cholangiocarcinoma should
      be discriminated by US, EUS, IDUS, and bile duct biopsy. CONCLUSION: For
      diagnosis of IgG4-SC, coexistence of AIP is the most useful finding. However, the
      most important consideration for clinicians is to be aware of IgG4-SC when
      encountering patients with obstructive jaundice.

PMID- 20814702
TI  - Letter to the editor concerning "nucleus pulposus deformation in response to
      lumbar spine lateral flexion: an in vivo MRI investigation" by Fazey PJ et al.
      (2010) Eur Spine J 19:1115-1120.

PMID- 20814703
TI  - Chlorophyll fluorescence imaging of plant-pathogen interactions.
AB  - Chlorophyll fluorescence imaging provides a noninvasive, non-destructive method
      with which to measure heterogenous changes in photosynthetic metabolism in plants
      infected by pathogens. The availability of commercial imaging fluorimeters has
      helped make this technique available to the wider scientific community, but
      considerable care is needed, both in experimental design and in the
      interpretation of results, to make the most of this powerful analytical tool. The
      origins of changes in chlorophyll fluorescence yield are discussed and the use of
      conventional and novel combinatorial imaging approaches explored, together with
      complementary techniques such as thermal imaging. This review examines the use of
      chlorophyll fluorescence imaging as a method for the early detection of viral,
      bacterial and fungal infection, before symptoms are visible by eye, and also as a
      means with which to probe underlying pathogen-induced changes in host physiology
      in both compatible and incompatible interactions. The use of chlorophyll
      fluorescence imaging to study host physiology is greatly enhanced when the
      atmosphere around the leaf is manipulated and simultaneous measurements of gas
      exchange made: The cost to the host plant of different resistance mechanisms can
      be calculated, the fate of the products of photosynthetic electron transport
      determined and localised alterations in the source-sink status of host tissue
      visualised.

PMID- 20814705
TI  - Epidemiology of hip fractures in Okinawa, Japan.
AB  - This study investigated the current incidence of hip fractures in Okinawa
      prefecture and compared the data with those obtained in our previous study, which
      was conducted using similar methods in 1987/1988. All patients, aged 50 years or
      older and residing in Okinawa, admitted to Okinawa hospitals in 2004 for a fresh
      hip fracture were identified from hospital registries. Details were obtained from
      the medical records and radiographs of all patients and classified according to
      fracture type (cervical or trochanteric), age, sex, and fracture location.
      Subtrochanteric fractures and pathological fractures were excluded. A total of
      1,349 patients (242 men and 1,107 women) were admitted for a fresh hip fracture
      in 2004. Their average age was 76.9 years for men and 82.4 years for women. There
      were 671 cervical fractures, 654 trochanteric fractures, and 24 unclassified
      proximal femoral fractures. Comparing the data from 1987/1988 to those from 2004,
      the total number of hip fractures increased by 188%, from 469 to 1,349. The age
      adjusted incidence rates per 100,000, standardized to the 2000 US population,
      were 75.7 and 296.1 in 1987/1988 and 123.6 and 420 in 2004 for men and women,
      respectively. The incidence rates in all age groups (at 5-year intervals) were
      higher in 2004 than in 1987/1988, indicating that people 50 years of age or older
      became more susceptible to hip fractures. Accordingly, the accretion of the hip
      fracture incidence rate was greater than that which could be explained purely by
      changes in population size and structure.

PMID- 20814706
TI  - Attention-deficit/hyperactivity disorder in perspective.

PMID- 20814704
TI  - Endocytosis in plant-microbe interactions.
AB  - Plants encounter throughout their life all kinds of microorganisms, such as
      bacteria, fungi, or oomycetes, with either friendly or unfriendly intentions.
      During evolution, plants have developed a wide range of defense mechanisms
      against attackers. In return, adapted microbes have developed strategies to
      overcome the plant lines of defense, some of these microbes engaging in
      mutualistic or parasitic endosymbioses. By sensing microbe presence and
      activating signaling cascades, the plasma membrane through its dynamics plays a
      crucial role in the ongoing molecular dialogue between plants and microbes. This
      review describes the contribution of endocytosis to different aspects of plant
      microbe interactions, microbe recognition and development of a basal immune
      response, and colonization of plant cells by endosymbionts. The putative
      endocytic routes for the entry of microbe molecules or microbes themselves are
      explored with a special emphasis on clathrin-mediated endocytosis. Finally, we
      evaluate recent findings that suggest a link between the compartmentalization of
      plant plasma membrane into microdomains and endocytosis.

PMID- 20814707
TI  - Prevalence of bullying and aggressive behavior and their relationship to mental
      health problems among 12- to 15-year-old Norwegian adolescents.
AB  - The aim of this study was to examine the relationships between being bullied and
      aggressive behavior and self-reported mental health problems among young
      adolescents. A representative population sample of 2,464 young Norwegian
      adolescents (50.8% girls) aged 12-15 years was assessed. Being bullied was
      measured using three items concerning teasing, exclusion, and physical assault.
      Self-esteem was assessed by Harter's self-perception profile for adolescents.
      Emotional and behavioral problems were measured by the Moods and Feelings
      Questionnaire (MFQ) and the youth self-report (YSR). Aggressive behavior was
      measured by four items from the YSR. One-tenth of the adolescents reported being
      bullied, and 5% reported having been aggressive toward others during the past 6
      months. More of the students being bullied and students being aggressive toward
      others reported parental divorce, and they showed higher scores on all YSR
      subscales and on the MFQ questions, and lower scores on the global self-worth
      subscale (Harter) than students not being bullied or aggressive. A few
      differences emerged between the two groups being bullied or being aggressive
      toward others: those who were aggressive showed higher total YSR scores, higher
      aggression and delinquency scores, and lower social problems scores, and reported
      higher scores on the social acceptance subscale (Harter) than bullied students.
      However, because social problems were demonstrated in both the involved groups,
      interventions designed to improve social competence and interaction skills should
      be integrated in antibullying programs.

PMID- 20814708
TI  - A PM6 study of Rhodopseudomonas Acidophila light harvesting center II B800
      bacteriochlorophylls in representative protein environment.
AB  - Bacterial light-harvesting II (LH-II) centers contain two types of
      Bacteriochlorophylls (Bchl). One is named B800 and found as a single molecule
      within one monomer of the complex while the other named B850 is found as a dimer.
      Their names indicate their peak of UV absorbance around red spectrum. Both types
      of molecules are attached to the protein chain via ligation of their central
      Magnesium atom to an either Histidine or Deoxymethionine amino acid. They are
      also coordinated by peripheral hydrogen bonds that they accept with their
      carboxyl side group. Both the ligation and the hydrogen bonding are thought to
      have an effect on electronic structure of the Bchl hence its UV absorbance and
      energy transfer rate. Experiments and theoretic studies performed on this subject
      support the above idea. This theoretical molecular modeling study case aims to
      mimic the experimental mutations performed on certain amino acids in silico and
      study its effects on the electronic structure of Bchl. By comparison with
      experimental results it was observed that the likely place for the nearby
      Arginine is not below the plane of the Bchl as in the X-ray crystallographic
      structure but above the plane defined by the four nitrogen atoms and their rings.
      It was also seen that the coordination of the acetyl group is very sensitive to
      changes in ligation of the Bchl molecule.

PMID- 20814709
TI  - Molecular analysis of linezolid resistance in clinical Enterococcus faecium
      isolates by polymerase chain reaction and pyrosequencing.
AB  - Resistance to linezolid has been associated with a G2576T mutation in the 23 S
      rRNA gene. Clinical isolates of linezolid-sensitive and linezolid-resistant
      vancomycin-resistant Enterococcus faecium of a liver transplant patient have been
      analysed for the G2576T mutation by polymerase chain reaction restriction
      fragment length polymorphism (PCR-RFLP), conventional sequencing and
      pyrosequencing. A clear association between the number of mutated 23 S rRNA genes
      and the level of linezolid resistance has been demonstrated. Linezolid
      susceptibility re-emerged after cessation of linezolid therapy; however, the re
      initiation of linezolid therapy resulted in the re-emergence of linezolid
      resistant strains. Pyrosequencing rapidly detected the number of mutated alleles
      and is superior to conventional PCR-RFLP for the detection of heterozygous
      mutations.

PMID- 20814710
TI  - Diagnostic accuracy of quantitative real-time PCR assay versus clinical and Gram
      stain identification of bacterial vaginosis.
AB  - The purpose of this investigation was to determine the diagnostic accuracy of
      quantitative real-time polymerase chain reaction (PCR) assay in diagnosing
      bacterial vaginosis versus the standard methods, the Amsel criteria and the
      Nugent score. The Amsel criteria, the Nugent score, and results from the
      molecular tool were obtained independently from vaginal samples of 163 pregnant
      women who reported abnormal vaginal symptoms before 20 weeks gestation. To
      determine the performance of the molecular tool, we calculated the kappa value,
      sensitivity, specificity, and positive and negative predictive values. Either or
      both of the Amsel criteria (>=3 criteria) and the Nugent score (score >=7)
      indicated that 25 women (15%) had bacterial vaginosis, and the remaining 138
      women did not. DNA levels of Gardnerella vaginalis or Atopobium vaginae exceeded
      10(9) copies/mL or 10(8) copies/mL, respectively, in 34 (21%) of the 163 samples.
      Complete agreement between both reference methods and high concentrations of G.
      vaginalis and A. vaginae was found in 94.5% of women (154/163 samples, kappa
      value = 0.81, 95% confidence interval 0.70-0.81). The nine samples with
      discordant results were categorized as intermediate flora by the Nugent score.
      The molecular tool predicted bacterial vaginosis with a sensitivity of 100%, a
      specificity of 93%, a positive predictive value of 73%, and a negative predictive
      value of 100%. The quantitative real-time PCR assay shows excellent agreement
      with the results of both reference methods for the diagnosis of bacterial
      vaginosis.

PMID- 20814711
TI  - Virulence factors profile of drug-resistant Escherichia coli isolates from
      urinary tract infections in Punjab, Pakistan.
AB  - Escherichia coli is considered to be the main causative agent of urinary tract
      infections (UTIs). The primary objective of this study was to investigate the
      spectrum of five virulence factors among drug-resistant clinical E. coli isolates
      associated with pyelonephritis and cystitis. A total of 101 samples were positive
      for E. coli (42 from pyelonephritis cases and 59 from cystitis cases) out of 457
      urine samples of patients. Among toxins, haemolysin and secreted autotransporter
      toxin are found more frequently in isolates causing pyelonephritis (p < 0.020)
      than cystitis (p < 0.083). The frequent occurrence of P-pili, S-fimbria and
      protein involved in intestinal colonisation was noted among E. coli isolates
      associated with pyelonephritis. Overall, the study suggests that clinical
      isolates associated with pyelonephritis are more virulent than those associated
      with cystitis and diversified association with various antimicrobial resistance
      phenotypes was noted.

PMID- 20814712
TI  - Frequency-domain near-infrared spectroscopy of the uterine cervix during regular
      pregnancies.
AB  - Preterm labor is a common obstetric complication. Clinical evaluation of cervical
      ripening to predict preterm labor is very inaccurate. We used frequency-domain
      near-infrared spectroscopy (FD-NIRS) to non-invasively investigate the changes of
      the optical properties (i.e., absorption and scattering of light) in the uterine
      cervix during regular pregnancies. Optical properties of uterine cervices were
      measured in 13 patients at various time points of regular pregnancies. For each
      gestational trimester, mean values with 95% confidence intervals were calculated
      for oxy-, deoxy-, and total hemoglobin concentration (O(2)Hb, HHb, tHb), tissue
      oxygen saturation and water content and statistically significant differences
      between the trimesters were determined. The wavelength-dependent scattering
      (scatter power) was calculated by an exponential fit. O(2)Hb, and tHb and the
      scatter power showed an increase as a function of the gestational age.
      Differences between the second and the third trimester were statistically
      significant. HHb and the water content showed no significant change over time.
      Our results show that FD-NIRS is a promising diagnostic tool for providing
      information about cervical content of hemoglobin, water, and extracellular matrix
      proteins. We propose this technology to assess the cervical ripening and
      eventually to predict preterm labor.

PMID- 20814713
TI  - Measuring antimicrobial susceptibility of Pseudomonas aeruginosa using Poloxamer
      407 gel.
AB  - Pseudomonas aeruginosa is a Gram-negative bacterium that causes various
      opportunistic infections. Chronic and intractable infections with P. aeruginosa
      are closely related to the high levels of resistance displayed by this organism
      to antimicrobial agents and its ability to form biofilms. Although the standard
      method for examining antimicrobial resistance involves susceptibility testing
      using Mueller-Hinton agar or broth, this method does not take into account the
      influence of biofilm formation on antimicrobial susceptibility. Poloxamer 407 is
      a hydrophilic, nonionic surfactant of the more general class of copolymers that
      can be used to culture bacteria with similar properties as cells in a biofilm
      environment. Therefore, the aim of this study was to compare the antimicrobial
      susceptibility of bacteria cultured in Poloxamer 407 gel to those grown on
      Mueller-Hinton agar using the Kirby-Bauer disk diffusion method with 24 strains
      of P. aeruginosa. Antimicrobial sensibility differed between the two mediums,
      with >60% of the strains displaying increased resistance to beta-lactams when
      cultured on Poloxamer 407 gel. In addition, scanning electron microscopy revealed
      that typical biofilm formation and extracellular polymeric substance production
      was only observed with bacteria grown on Poloxamer 407 gel. Therefore,
      antimicrobial susceptibility test using Poloxamer 407 gel may provide more
      accurate information and allow the selection of suitable antimicrobial agents for
      treating patients infected with biofilm-forming pathogens.

PMID- 20814714
TI  - Periurethral abscess complicating gonococcal urethritis: case report and
      literature review.

PMID- 20814715
TI  - Reflections on community-based population health intervention and evaluation for
      obesity and chronic disease prevention: the Healthy Alberta Communities project.
AB  - OBJECTIVES: To reflect upon a population health intervention for obesity and
      chronic disease prevention, with specific attention to the processes of change
      and developing, implementing and evaluating an intervention in a community
      university-government partnership context. METHODS: To capture the value, process
      and context of our interventions, we employed a multi-layered, mixed methods
      research and evaluation design. Guided by assumptions of community-based
      participatory research, and using a validated capacity-building tool, the
      investigators described and reflected critically upon the level and nature of
      capacity built (for both research and intervention) as indicators of the process
      and contextual influences on intervention success. RESULTS: Capacity was built in
      communities through collaborative approaches. We captured complexity of change in
      social context to advance understanding of how to intervene to transform
      environments. Developing novel community evaluation strategies can help to
      advance understanding of how environmental interventions affect health before
      health outcomes data demonstrate change. CONCLUSIONS: Our experience provides an
      example of operationalizing an ecological framework. As a community-university
      government partnership, Healthy Alberta Communities provides an opportunity for
      developing promising practices for the health of communities, as well as a unique
      research platform for evaluating the process and establishing effectiveness of
      population health interventions.

PMID- 20814716
TI  - Production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) by Cupriavidus necator
      from waste rapeseed oil using propanol as a precursor of 3-hydroxyvalerate.
AB  - Waste rapeseed oil is a useful substrate for polyhydroxyalkanoates (PHA)
      production employing Cupriavidus necator H16. In fed-batch mode, we obtained
      biomass and PHA yields of 138 and 105 g l(-1), respectively. Yield coefficient
      and volumetric productivity were 0.83 g PHA per g oil and 1.46 g l(-1) h(-1),
      respectively. Propanol at 1% (v/v) enhanced both PHA and biomass formation
      significantly and, furthermore, resulted in incorporation of 3-hydroxyvalerate
      units into PHA structure. Thus, propanol can be used as an effective precursor of
      3-hydroxyvalarete for production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate)
      copolymer. During the fed-batch cultivation, propanol concentration was
      maintained at 1% which resulted in 8% content of 3-hydroxyvalerate in copolymer.

PMID- 20814717
TI  - Trainable structure-activity relationship model for virtual screening of CYP3A4
      inhibition.
AB  - A new structure-activity relationship model predicting the probability for a
      compound to inhibit human cytochrome P450 3A4 has been developed using data for
      >800 compounds from various literature sources and tested on PubChem screening
      data. Novel GALAS (Global, Adjusted Locally According to Similarity) modeling
      methodology has been used, which is a combination of baseline global QSAR model
      and local similarity based corrections. GALAS modeling method allows forecasting
      the reliability of prediction thus defining the model applicability domain. For
      compounds within this domain the statistical results of the final model approach
      the data consistency between experimental data from literature and PubChem
      datasets with the overall accuracy of 89%. However, the original model is
      applicable only for less than a half of PubChem database. Since the similarity
      correction procedure of GALAS modeling method allows straightforward model
      training, the possibility to expand the applicability domain has been
      investigated. Experimental data from PubChem dataset served as an example of in
      house high-throughput screening data. The model successfully adapted itself to
      both data classified using the same and different IC50 threshold compared with
      the training set. In addition, adjustment of the CYP3A4 inhibition model to
      compounds with a novel chemical scaffold has been demonstrated. The reported
      GALAS model is proposed as a useful tool for virtual screening of compounds for
      possible drug-drug interactions even prior to the actual synthesis.

PMID- 20814718
TI  - Proteomic analysis of lanthanum citrate-induced apoptosis in human cervical
      carcinoma SiHa cells.
AB  - Lanthanides possess diverse biological effect and have been shown to promote cell
      proliferation and induce apoptosis. Our previous studies showing that lanthanide
      citrate complex has significant antitumor activity in human cervical cancer HeLa
      cells. This study aims at determining if [LaCit(2)](3-) have the activity against
      another type of human cervical cancer cell line SiHa and the changes in protein
      expression that contribute to the mechanism(s) of [LaCit(2)](3-)-mediated
      apoptosis in SiHa cells. Cell growth inhibition was measured by MTT method, and
      apoptosis was detected by means of Hoechst 33258 staining and flow cytometry
      analysis. After [LaCit(2)](3-)-treatment the results show that the growth of SiHa
      cells was inhibited, the cells displayed typical apoptosis morphological changes,
      and increase in the rates of apoptosis. Using proteomics approaches, a variety of
      differentially expressed proteins were identified in SiHa cells before and after
      treatment with [LaCit(2)](3-). There were profound changes in 10 proteins
      relating to mitochondrial function and oxidative stress, suggesting that
      mitochondrial dysfunction plays a key role in [LaCit(2)](3-)-induced apoptosis.
      This was confirmed by a decrease in the mitochondrial transmembrane potential
      (Deltapsi(m)), and increases in H(2)O(2) generation in [LaCit(2)](3-)-treated
      cells. Among them the alerted proteins, Prx I, ANXA1 and TRAF5 were validated by
      western blotting analyses. These results suggest that there is an intrinsic
      molecular pathway of cell apoptosis in [LaCit(2)](3-)-treated SiHa cells. This
      observation is in accordance with our previous reports about the effects of
      [LaCit(2)](3-) and [YbCit(2)](3-) on HeLa cells and it provide a molecular
      mechanism underlying lanthanide citrate complex-mediated cell apoptosis.

PMID- 20814719
TI  - Expression of tenascin-C and its isoforms in the breast.
AB  - Tenascin-C (TNC) is an extracellular matrix glycoprotein which is frequently up
      regulated in a variety of pathological conditions including chronic inflammation
      and cancer. TNC has been implicated in the modulation of cell migration,
      proliferation, invasion and angiogenesis. Multiple isoforms of TNC can be
      generated through the alternative splicing of nine exons located in the
      fibronectin type III region of the molecule. The profile of isoforms expressed
      differs between cancers and normal breast, with the fully truncated TNC isoform
      being predominant in normal and benign tissues and higher molecular weight
      isoforms induced predominantly in cancer. The addition of extra domains within
      the fibronectin type III repeat domain greatly affects TNC function with multiple
      exon combinations available for splicing. Exons 14 and 16 are considered to be
      tumour-associated and have been shown to affect breast cell line invasion and
      growth in vitro to a greater extent than the full-length TNC isoform. This mini
      review will provide a summary of the literature to date regarding the expression
      of TNC isoforms in the breast and also discuss more recent developments in the
      field regarding exon AD1.

PMID- 20814720
TI  - Nanotechnology-based cancer therapeutics--promise and challenge--lessons learned
      through the NCI Alliance for Nanotechnology in Cancer.
AB  - The new generation of nanotechnology-based drug formulations is challenging the
      accepted ways of cancer treatment. Multi-functional nanomaterial constructs have
      the capability to be delivered directly to the tumor site and eradicate cancer
      cells selectively, while sparing healthy cells. Tailoring of the nano-construct
      design can result in enhanced drug efficacy at lower doses as compared to free
      drug treatment, wider therapeutic window, and lower side effects. Nanoparticle
      carriers can also address several drug delivery problems which could not be
      effectively solved in the past and include reduction of multi-drug resistance
      effects, delivery of siRNA, and penetration of the blood-brain-barrier. Although
      challenges in understanding toxicity, biodistribution, and paving an effective
      regulatory path must be met, nanoscale devices carry a formidable promise to
      change ways cancer is diagnosed and treated. This article summarizes current
      developments in nanotechnology-based drug delivery and discusses path forward in
      this field. The discussion is done in context of research and development
      occurring within the NCI Alliance for Nanotechnology in Cancer program.

PMID- 20814721
TI  - Economic and quality scheduling for effective utilization of operating rooms.
AB  - Under the constraints of limited medical resources and severe competition among
      hospitals, administrators have begun to pay attention to the opportunities of
      cost reduction and quality improvement in hospital management, in order to find
      methods to increase hospital revenue and improve service quality. The operating
      room should be one of the most important sources of hospital income, yet it is
      both costly to run and constrictive to inpatient flow. Successful hospital
      management necessitates the construction of cost-effective and quality operating
      room scheduling. This paper attempts to model the scheduling problem in the form
      of mathematical programming with the objective being to minimize the deviation
      between the total operation time and the total available time in operating rooms.
      Urgent revisions to the model in consideration of such factors as doctor's
      availability, outpatient consulting hours and unfavorable surgery hours can be
      achieved in a timely manner. With the present approach, surgical procedures can
      start punctually, inpatient waiting time for surgery and length of stay can be
      reduced, and staff morale can be enhanced. These improvements will result in cost
      reduction, and increased hospital revenue without sacrificing the quality of
      medical care.

PMID- 20814722
TI  - Multi-feature characterization of epileptic activity for construction of an
      automated internet-based annotated classification.
AB  - Continuous monitoring of EEG is essential for the neurologist to detect the
      epileptic seizures that occur at various intervals. Since large volume of data
      need to be analyzed, visual analysis has been proven to be time consuming and
      subsequently automated detection techniques have gained importance in the recent
      years. For the biomedical research community, the major challenge lies in
      providing a solution to neurologists in terms of diagnosis and EEG database
      management. This paper discusses the automated detection of epileptic seizure
      using frequency domain and entropy parameters which helps in the construction of
      epileptic database for handling EEG data. Experimental study indicates that the
      suggested mode of operation can be used for internet based framework which
      contains pure epileptic patterns in the server. This can be retrieved and
      analyzed for detection and annotation of epileptic spikes in extensive EEG
      recordings.

PMID- 20814723
TI  - Distinct photoacidity of honokiol from magnolol.
AB  - Honokiol, 5,5'-diallyl-2,4'-dihydroxy- biphenyl, by comparison with its isomer
      magnolol, 5,5'-diallyl- 2,2'-dihydroxy- biphenyl, has been characterized by
      steady-state and time-resolved spectroscopy as well as (1)H NMR. Honokiol shows
      more complex pH dependence of absorption and fluorescence characteristics
      compared with magnolol. Honokiol possesses much weaker acidity than magnolol both
      in the ground and excited states. Its weak photoacidity is similar to that of 4
      hydroxy- biphenyl or 4, 4'-dihydroxy- biphenyl rather than 2-hydroxy- biphenyl or
      2, 2'-hydroxy- biphenyl. The electron effect and geometry configuration of
      substitution has been discussed.

PMID- 20814724
TI  - Semisynthesis of a protein with cholesterol at the C-terminal, targeted to the
      cell membrane of live cells.
AB  - Various proteins are modified post-translationally to localize them at the cell
      membrane. Among them, hedgehog-family proteins are modified by cholesterol at the
      C-terminal. In this study, green fluorescent protein (GFP) modified with
      cholesterol (GFP-Chol) at the C-terminal was prepared semisynthetically and
      investigated. This semi-synthesis was performed using the following native
      chemical ligation: GFP-Calpha-thioester was prepared using the intein-mediated
      thioester exchange reaction and was ligated to Cys-NH-diethylene glycol-NHCO
      cholesterol in the presence of a detergent. After removal of the detergent, the
      GFP-Chol was applied to mouse live cells. Confocal laser fluorescent microscopy
      confirmed localization of GFP-Chol at the cell membrane. The findings suggest
      that modifying proteins with cholesterol at the C-terminal is useful for
      targeting the proteins to the cell membrane of live cells.

PMID- 20814725
TI  - Purification and characterization of thermophilic xylanase isolated from the
      xerophytic-Cereus pterogonus sp.
AB  - A thermo stable xylanase was purified and characterized from the cladodes of
      Cereus pterogonus plant species. The enzyme was purified to homogeneity by
      ammonium sulfate (80%) fractionation, ion exchange and size exclusion
      chromatography. The enzyme showed a final specific activity of 216.2 U/mg and the
      molecular mass of the protein was 80 KDa. The optimum pH and temperature for
      xylanase activity were 5.0 and 80  degrees C, respectively. With oat spelt xylan
      as a substrate the enzyme yielded a Km value of 2.24 mg/mL and a Vmax of 5.8
      MUmol min(-1) mg(-1). In the presence of metal ions (1 mM) such as Co(2+),Mn(2+),
      Ni(2+), Ca(2+) and Fe(3+) the activity of the enzyme increased, where as strong
      inhibition of the enzyme activity was observed with the use of Hg(2+), Cd(2+),
      Cu(2+), while partial inhibition was noted with Zn(2+) and Mg(2+). The substrate
      specificity of the xylanase yielded maximum activity with oat spelt xylan.

PMID- 20814726
TI  - A community engagement process for families with children with disabilities:
      lessons in leadership and policy.
AB  - This article examines a community engagement process developed as part of
      leadership training for clinical trainees in the Oregon Leadership Education for
      Neurodevelopmental and Related Disabilities (LEND) Program in a complex community
      with diverse families who have children with disabilities. The goal is to examine
      the process and lessons learned for clinical trainees and their mentors from such
      a process. This is a case study conducted as community-engaged action research by
      participant-observers involved in the Cornelius community for the past 4 years.
      The authors include faculty members and clinical trainees of the Oregon LEND
      Program at the Oregon Health & Science University, families with children with
      disabilities in the community, and city officials. It is a critical case study in
      that it studied a community engagement process in one of the poorest communities
      in the region, with an unusually high population of children with disabilities,
      and in a community that is over half Latino residents. Lessons learned here can
      be helpful in a variety of settings. Community engagement forum, community
      engagement processes, a debriefing using a seven-element feasibility framework,
      and trainee evaluations are key elements. A community engagement forum is a
      meeting to which community members and stakeholders from pertinent agencies are
      invited. Community engagement processes used include a steering committee made up
      of, and guided by community members which meets on a regular basis to prioritize
      and carry out responses to problems. Trainee evaluations are based on a set of
      questions to trigger open-ended responses. Lessons learned are based on
      assessments of initial and long-term outcomes of the community engagement
      processes in which families, community members, local officials and LEND trainees
      and faculty participate as well as by trainee participant-observations, end of
      year evaluations and trainee debriefings at the time of the initial community
      assessment forum. The thesis that emerges is that community engagement processes
      can afford significant opportunities for clinicians in training to develop their
      leadership skills toward improving maternal and child health for minority
      families with children with disabilities while building capacity in families for
      advocacy and facilitating change in the community.

PMID- 20814727
TI  - Impact of biological control agents on fusaric acid secreted from Fusarium
      oxysporum f. sp. gladioli (Massey) Snyder and Hansen in Gladiolus grandiflorus
      corms.
AB  - Fusaric acid (FA) (5-n-butylpuridine 2-carboxyl acid), a highly toxic secondary
      metabolite produced by Fusarium oxysporum strains, plays a significant role in
      disease development. The abilities of three F. oxysporum f. sp. gladioli (Massey)
      Snyder and Hansen isolates (G010; 649-91; and 160-57) to produce FA in infected
      Gladiolus corm tissues was evaluated in vitro in relation to the presence of two
      biological control agents, Trichoderma harzianum T22, and Aneurinobacillus
      migulanus. Pathogenicity tests were used to differentiate between the abilities
      of the F. oxysporum strains to secrete FA. FA was identified using LC/MS and
      quantified using HPLC. Isolate G010 was significantly more virulent (P < 0.01) on
      Gladiolus grandiflorus corms; it secretes 1.8 MUM FA/g fresh weight corm into
      inoculated Gladiolus. Moreover, G010 was the only isolate that produced FA among
      the three examined isolates. There was a correlation between the corm lesion area
      and the FA secretion ability of F. oxysporum f. sp. gladioli (P < 0.001; r (2) =
      0.96). No FA was detected in PDA cultures of F.oxysporum f. sp. gladioli
      isolates. The presence of T. harzianum T22 appeared to prevent FA secretion into
      the corms. In the presence of A. migulanus, however, the amount of FA secreted
      into the corm tissues increased. These results support the use of T. harzianum as
      an effective biological control agent against F. oxysporum f. sp. gladioli.

PMID- 20814728
TI  - Use of interdelta polymorphisms of Saccharomyces cerevisiae strains to monitor
      population evolution during wine fermentation.
AB  - The industrial use of starter cultures containing a consortium of different
      strains from the same species is nowadays seen as a possible strategy to enhance
      the organoleptic complexity of wines. To assess the relative contribution of each
      strain to the final product it is essential to quantify population evolution
      during the wine fermentation process, which requires strain-specific methods to
      identify and differentiate each strain. In the present study, a molecular method
      based on analysis of the polymorphisms exhibited by the PCR-amplification of the
      delta regions of three Saccharomyces cerevisiae strains was developed. A set of
      three pairs of primers (delta1-delta2, delta12-delta2, delta12-delta21) was used
      for each strain, and analysis of the resulting polymorphism patterns showed that
      the delta12-delta2 primer pair exhibited the highest resolution and
      discriminatory power. Thus, this pair of primers was selected to monitor the
      population evolution of a laboratory-scale wine fermentation performed in
      synthetic grape juice that was inoculated with similar amounts of each strain.
      The results showed that all strains grew together during the exponential growth
      phase (2-3 days) and maintained high cell density values (10(6)-10(7) cfu ml(-1))
      throughout the stationary growth phase without significantly changing their
      relative population proportion, thus indicating that each strain can influence
      the chemical composition and final flavor of wine, albeit at different levels.
      This study also showed that PCR-amplification of DNA delta sequences of S.
      cerevisiae strains is a reproducible, strain-specific and simple method that can
      be used successfully to monitor yeast strain population dynamics during wine
      fermentations.

PMID- 20814729
TI  - Growth kinetics of biopigment production by Thai isolated Monascus purpureus in a
      stirred tank bioreactor.
AB  - Monascus purpureus is a biopigment-producing fungi whose pigments can be used in
      many biotechnological and food industries. The growth kinetics of biopigment
      production were investigated in a liquid fermentation medium in a 5-l stirred
      tank bioreactor at 30 degrees C, pH 7, for 8 days with 100 rpm agitation and 1.38
      * 10(5) N/m(2) aeration. Thai Monascus purpureus strains TISTR 3002, 3180, 3090
      and 3385 were studied for color production, growth kinetics and productivity.
      Citrinin as a toxic metabolite was measured from the Monascus fermentation broth.
      The biopigment productions were detected from fermentation broth by scanning
      spectra of each strain produced. Results showed a mixture of yellow, orange and
      red pigments with absorption peaks of pigments occurring at different wavelengths
      for the four strains. It was found that for each pigment color, the color
      production from the strains increased in the order TISTR 3002, 3180, 3090, 3385
      with 3385 production being approximately 10 times that of 3002. Similar results
      were found for growth kinetics and productivity. HPLC results showed that
      citrinin was not produced under the culture conditions of this study. The L*, a*
      and b* values of the CIELAB color system were also obtained for the yellow,
      orange and red pigments produced from the TISTR 3002, 3180, 3090 and 3385
      strains. The colors of the pigments ranged from burnt umber to deep red.

PMID- 20814730
TI  - Enhancement of extracellular purine nucleoside accumulation by Bacillus strains
      through genetic modifications of genes involved in nucleoside export.
AB  - Using a simple method to introduce genetic modifications into the chromosome of
      naturally nontransformable Bacillus, a set of marker-free inosine-producing and 5
      aminoimidazole-4-carboxamide (AICA) ribonucleoside-producing Bacillus
      amyloliquefaciens strains has been constructed. These strains differ in
      expression levels of the genes responsible for nucleoside export. Overexpression
      of B. amyloliquefaciens pbuE and heterologous expression of Escherichia coli
      nepI, which encode nucleoside efflux transporters, each notably enhanced inosine
      production by a B. amyloliquefaciens nucleoside-producing strain. pbuE
      overexpression was found to increase AICA ribonucleoside accumulation, indicating
      that the substrate specificity of the PbuE pump extends to this nucleoside. These
      results demonstrate that identifying genes whose products facilitate transport of
      a desired nucleoside out of cells and enhancing their expression can improve the
      performance of strains used for industrial production.

PMID- 20814731
TI  - 3beta-acetyl tormentic acid induces apoptosis of resistant leukemia cells
      independently of P-gp/ABCB1 activity or expression.
AB  - Chronic myeloid leukemia (CML) is a potentially fatal stem-cell cancer. P
      glycoprotein (P-gp/ABCB1) activity has been described as a relevant factor in the
      chemotherapeutic failure and correlated to a poor prognosis in these
      malignancies. In the present study, we investigated the mechanism of the
      antineoplastic activity of 3beta-acetyl tormentic acid (3ATA), a triterpene
      isolated from C. lyratiloba, on Lucena-1, an MDR leukemia cell line, that
      overexpressed P-gp/ABCB1. Results showing that this triterpene induced DNA
      fragmentation, activation of caspase-3 and cytochrome c release indicated that
      its activity is mediated by the activation of the intrinsic pathway of apoptosis.
      Interestingly, this triterpene did not interfere with P-gp/ABCB1 expression or
      activity, indicating that induction of death is not mediated by any effect on
      this protein. Moreover, the results show that none of the others triterpenes from
      C. lyratiloba were able to modulate the activity of P-gp/ABCB1. Together these
      results suggest 3ATA and the other triterpenes as a promising material for the
      development of anti-neoplastic drugs for leukemia and other tumors independent of
      P-gp/ABCB1 activity or expression.

PMID- 20814732
TI  - 17alpha-alkynyl 3alpha, 17beta-androstanediol non-clinical and clinical
      pharmacology, pharmacokinetics and metabolism.
AB  - 17alpha-ethynyl-5alpha-androstane-3alpha, 17beta-diol (HE3235, Apoptone) is an
      orally bioavailable synthetic analogue of 3beta-androstanediol, that is active in
      rodent models of prostate and breast cancer, and is in Phase IIa clinical trials
      for the treatment of early- and late-stage prostate cancer. In preparation for
      clinical studies, nuclear hormone receptor and P450 interactions for HE3235 and
      major metabolites were characterized in vitro, and pharmacokinetics and
      metabolite profiles were studied in rodents, dogs, and monkeys. Four-week safety
      studies conducted in rats and dogs indicated a substantial margin of safety for
      clinical use, and no evidence of electrocardiographic or neurological effects,
      although anorexia, thrombocytopenia, and hypokalemia were identified as
      potentially dose-limiting toxicities at superpharmacological exposures.
      Pharmacokinetics and drug metabolism have been studied in prostate cancer
      patients.

PMID- 20814733
TI  - Radiofrequency ablation of coronary sinus-dependent atrial flutter guided by
      fractionated mid-diastolic coronary sinus potentials.
AB  - BACKGROUND: The efficacy of radiofrequency (RF) ablation of an uncommon coronary
      sinus (CS)-dependent atrial flutter (AFL) was evaluated using conventional
      electrophysiological criteria in a highly selected subset of patients with
      typical and atypical AFL. METHODS: Fourteen patients with atrial flutter (11
      males, mean age 69 +/- 9 years) without previous right or left atrial RF ablation
      were included. Heart disease was present in eight patients. Baseline ECG
      suggested typical AFL in 12 patients and atypical AFL in two. Mean AFL cycle
      length was 324 +/- 64 ms at the time of RF ablation in the CS. Lateral right
      atrium activation was counterclockwise (CCW) in 13 patients and clockwise in one.
      CS activation was CCW in all. Criteria for CS ablation included the presence of
      CS mid-diastolic fractionated atrial potentials (APs) associated with concealed
      entrainment with a postpacing interval within 20 ms. Success was defined as
      termination of AFL and subsequent noninducibility. RESULTS: The initial target
      for ablation was the cavotricuspid isthmus (CTI) in 11 patients and the CS with
      further CTI ablation in three. AP duration at the CS target site was 122 +/- 33
      ms, spanning 40 +/- 12% of the AFL cycle length. CS ablation site was located 1-4
      cm from the CS ostium. Ablation was successful in all patients. Mean time to AFL
      termination during CS ablation was 39 +/- 52 s (<20 s in eight patients). No
      recurrence of ablated arrhythmia occurred during a follow-up of 18 +/- 8 months.
      CONCLUSIONS: The CS musculature is a critical part of some AFL circuits in
      patients with typical and atypical AFL. AFL can be terminated in patients with CS
      or CTI/CS AFL reentrant circuits by targeting CS mid-diastolic fragmented APs.

PMID- 20814734
TI  - Cytochrome P450 pathway contributes to methanandamide-induced vasorelaxation in
      rat aorta.
AB  - PURPOSE: The generation of hyperpolarising vasorelaxant endothelial cytochrome
      P450 epoxygenase (CYP)-derived metabolites of arachidonic may provide beneficial
      effects for the treatment of cardiovascular diseases in which the bioavailability
      of NO is impaired. The cannabinoid methanandamide has vasodilatory properties
      linked to hyperpolarisation. The aim of the present work was to investigate the
      vasorelaxant effects of methanandamide in rat aorta, focusing on the role of
      cytochrome P450 pathway. METHODS: Changes in isometric tension in response to a
      cumulative concentration-response curve of methanandamide (1 nM-100 MUM) were
      recorded in aortic rings from male Wistar rats. The involvement of cannabinoid
      receptors, endothelial nitric oxide (NO)-, prostacyclin- and some hyperpolarising
      mediated pathways were investigated. The activation of large-conductance Ca(2+)
      activated K(+) (BKCa) channels have also been evaluated. RESULTS: Methanandamide
      provoked an endothelium-dependent vasorelaxation in rat aorta, reaching a maximal
      effect (Rmax) of 67% +/- 2.6%. This vasorelaxation was clearly inhibited by the
      combination of CB(1) and CB(2) cannabinoid antagonists (Rmax: 21.6% +/- 1.3%) and
      by the combination of guanylate cyclase and CYP inhibitors (Rmax: 16.7% +/-
      1.1%). The blockade induced separately by guanylate cyclase (31.3% +/- 2.8%) or
      CYP (36.3% +/- 6.6%) inhibitors on methanandamide vasorelaxation was not
      significantly modified by either CB(1) or CB(2) inhibition. BKCa channels
      inhibition caused a partial and significant inhibition of the methanandamide
      vasorelaxation (Rmax: 39.9% +/- 3.3%). CONCLUSIONS: Methanandamide endothelium
      dependent vasorelaxation is mediated by CB(1) and CB(2) cannabinoid receptors.
      The NO- and CYP-mediated pathways contribute in a concurrent manner in this
      vascular effect. Stimulation of both cannabinoid receptor subtypes is
      indistinctly linked to NO or CYP routes to cause vasorelaxation.

PMID- 20814735
TI  - Patient and program predictors of 12-month outcomes for homeless veterans
      following discharge from time-limited residential treatment.
AB  - The U.S. Department of Veterans Affairs provides transitional residential
      treatment to homeless veterans through three types of programs: VA-staffed
      Domiciliary care, and two types of community-based treatment (one funded through
      locally managed contracts and the other through national grants). This study
      compared treatment process and outcomes in these three programs and also sought
      to identify differences in outcome between dually diagnosed veterans, veterans
      with substance abuse problems or psychiatric problems alone, and those with no
      psychiatric diagnoses. Altogether, 1,338 veterans admitted to the 3 types of
      program were recruited to participate in a prospective naturalistic study which
      evaluated housing, clinical and community adjustment outcomes during the year
      following discharge. Data on 1,003 veterans for whom psychiatric diagnostic,
      social climate and length of stay data were available were used to compare
      participants in the three program types at baseline. Regression models were used
      to compare outcomes across program and diagnostic types net of baseline
      differences between study participants, and of differences in social climate and
      length of stay. The overall follow-up rate across all time points was 72%.
      Significant differences across programs were observed on only 2 baseline measures
      as well as on several baseline values of the outcome measures, length of stay and
      a measure of social climate. Adjusting for veteran baseline differences alone
      there were no differences in outcomes by program after correction for multiple
      comparisons. Dually diagnosed veterans had poorer mental health and overall
      quality of life outcomes. Longer length of stay and more positive social climate
      were associated with superior outcomes on several measures. The adjusted mean
      estimate of the proportion of veterans housed at 12 months follow-up was 78%,
      similar to published outcomes for supported housing. Length of stay, rather than
      program funding configuration or diagnostic group, was the strongest predictor of
      outcomes in time-limited residential treatment programs in which 1-year housing
      was similar to those in direct-placement supported housing programs.

PMID- 20814736
TI  - Recreational physical activity, anthropometric factors, and risk of ductal
      carcinoma in situ of the breast in a cohort of postmenopausal women.
AB  - OBJECTIVE: To assess the association of recreational physical activity and
      anthropometric factors in relation to risk of ductal carcinoma in situ (DCIS) of
      the breast. METHODS: The association was examined in a cohort of 58,055
      postmenopausal women participating in the Women's Health Initiative (WHI)
      clinical trials, among whom 450 cases of DCIS were ascertained after a median
      follow-up of 8.0 years. Cox proportional hazard models were used to estimate
      hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS: After
      adjustment for covariates, the hazard ratio for DCIS among women with >= 20
      metabolic equivalent task-hours per week (MET-h/week) of total recreational
      physical activity compared to women who did not engage in any recreational
      physical activity (0 MET-h/week) was 0.97 (95% CI 0.70-1.34). Neither body mass
      index nor waist circumference was associated with risk. In addition, physical
      activity and anthropometric factors were not associated with risk of either high
      grade or low-/moderate-grade DCIS. CONCLUSIONS: Recreational physical activity
      and anthropometric factors showed no association with risk of DCIS in
      postmenopausal women in the WHI clinical trial.

PMID- 20814737
TI  - Psychopathic traits of Dutch adolescents in residential care: identifying
      subgroups.
AB  - The present study examined whether a sample of 214 (52.8% male, M age = 15.76, SD
      = 1.29) institutionalized adolescents could be classified into subgroups based on
      psychopathic traits. Confirmatory Factor Analyses revealed a relationship between
      the subscales of the Youth Psychopathic traits Inventory (YPI) and the three
      latent constructs of the original model on which it is based. Latent Class
      Analyses showed that adolescents showing psychopathic traits could be classified
      into three subgroups. The first group showed low scores on the
      grandiose/manipulative dimension, the callous/unemotional dimension, and the
      impulsive/irresponsible dimension (normal group). The second group scored
      moderate on the grandiose/manipulative dimension and the callous/unemotional
      dimension and high on the impulsive/irresponsible dimension (impulsive, non
      psychopathic-like group). The third group scored high on all three dimensions
      (psychopathy-like group). The findings revealed that the impulsive, non
      psychopathic like group scored significantly higher on internalizing problem
      behavior compared to the normal group, while the psychopathy-like and the
      impulsive, non-psychopathic-like group both scored higher on externalizing
      problem behavior compared to the normal group. Based on a self-report delinquency
      measure, it appeared that the psychopathy-like group had the highest delinquency
      rates, except for vandalism. Both the impulsive and psychopathy-like group had
      the highest scores on the use of soft drugs.

PMID- 20814738
TI  - Bioassay as monitoring system for lead phytoremediation through Crinum asiaticum
      L.
AB  - Toxicity of lead in soil is well documented and established. Phytoremediation has
      gained attention as a cheap, easily applicable, and eco-friendly clean-up
      technology. Chemical methods are used to assess exact levels and type of
      pollutants but heavy metal content in soil can also be evaluated indirectly by
      estimation of phytotoxicity levels using bioassays. Plant bioassays through fast
      germinating cereals can indicate not only the level of pollution and its effects
      on growth and survival but also the progress of phytoremediation process. The
      performance of barley Hordeum vulgare L. seedlings as bioassay for assessment of
      changes in the levels of lead (Pb) at three concentrations, i.e., 300 (T(1)), 600
      (T(2)), and 1,200 ppm (T(3)) in the soil was evaluated while testing the
      efficiency of Crinum asiaticum L. as a phytoremedial tool. At the first
      assessment, i.e., 30 DAT (days after treatment) shoot and root lengths of
      seedlings decreased with increasing concentrations of Pb. As the study
      progressed, a decrease in levels of Pb was accompanied by better germinability
      and growth of barley. At 120 DAT seedling growth in all the treatments were
      comparable to control. In T(1), T(2), and T(3) soils, 74.5%, 83.7%, and 91.2%
      reduction in lead content was observed at 120 DAT. Highly significant
      correlations between decreasing pollutant (Pb) content in the soil, seed
      germination, and seedling growth of barley H. vulgare were found. The differences
      in root and shoot length as well as overall growth pattern are indicative of the
      suitability of barley as a bio-monitoring tool.

PMID- 20814739
TI  - Review of PSR framework and development of a DPSIR model to assess greenhouse
      effect in Taiwan.
AB  - In dealing with the complex issues of greenhouse gas (GHG) emission and climate
      change mitigation, many interrelated factors such as cost, level of technology
      development, supply and demand of energy, structure of industry, and expenditures
      on research and development exist. Using indicators to monitor environmental
      impacts and evaluate the efficacies of policies and regulations has been
      practiced for a long time, and it can serve as a useful tool for decision making
      and for comparison between different countries. Although numerous indicators have
      been developed for relevant subjects, integrated approaches that consider
      individual changes, dynamic interaction, and multi-dimensions of indicators are
      scarce. This paper aimed to develop a Driving Force-Pressure-State-Impact
      Response (DPSIR) framework to assess the problems. This DPSIR model is mainly
      related to energy consumption, environmental impacts, and policy responses. The
      objectives of the paper were: (1) conduct a literature review on the indicators
      that have been used in GHG-related studies; (2) develop a DPSIR model that
      incorporates GHG-related indicators and evaluate their relationships using a
      cause-effect chain of GHG emission; and (3) develop a calculative method that can
      be used to explain the dynamic correlation among the interdependent indicators.
      Taiwan is a significant source of global GHG emissions. A case study, using the
      developed framework and Taiwan's actual data of the past two decades, was
      conducted. The results indicate that regulatory strategies for pollution control
      are inadequate in terms of ensuring environmental quality, and the nature does
      not have the capability to revert the impacts from the existing level of
      pollution.

PMID- 20814740
TI  - Alpha-lipoic acid modulates GFAP, vimentin, nestin, cyclin D1 and MAP-kinase
      expression in astroglial cell cultures.
AB  - In the present study, we evaluated the expression of some proliferation and
      differentiation markers in 15 DIV astrocyte cultures pretreated or not with 0.5
      mM glutamate for 24 h and than maintained under chronic or acute treatment with
      50 MUM R(+)enantiomer or raceme alpha-lipoic acid (ALA). GFAP expression
      significantly increased after (R+)enantiomer acute-treatment and also in
      glutamate-pretreated ones. Vimentin expression increased after R(+)enantiomer
      acute-treatment, but it decreased after raceme acute-treatment. Nestin expression
      drastically increased after acute raceme-treatment in glutamate-pretreated or not
      cultures, but significantly decreased after (R+)enantiomer acute and chronic
      treatments. Cyclin D1 expression increased in raceme acute-treated cultures
      pretreated with glutamate. MAP-kinase expression slightly increased after
      (R+)enantiomer acute treatment in glutamate-pretreated or unpretreated ones.
      These preliminary findings may better clarify antioxidant and metabolic role
      played by ALA in proliferating and differentiating astrocyte cultures suggesting
      an interactive cross-talk between glial and neuronal cells, after brain lesions
      or damages.

PMID- 20814741
TI  - Detection of reaginic antibodies against Faenia rectivirgula from the serum of
      horses affected with Recurrent Airway Obstruction by an in vitro bioassay.
AB  - Reaginic antibodies, mainly of the IgE and some IgG subclasses, play an important
      role in the induction of type I immediate hypersensitivity reactions. These
      antibodies bind through their Fc fragment to high affinity receptors
      (FcepsilonRI) present in the membrane of mast cells and basophils. Previously,
      several studies have investigated the role of reaginic antibodies in the
      pathogenesis of RAO. However, whereas immunological aspects of RAO have been
      extensively studied, the precise sequence of events is still not well understood
      and role of IgE in this disease still remains controversial. Therefore, in this
      study a bioassay was developed for reaginic antibody determination in serum from
      RAO-affected horses in order to determine the etiology of disease. The technique
      involves measuring in vitro calcium mobilization in RBL-2H3 cells following
      incubation with horse serum from RAO-affected or unaffected horses and one of the
      RAO antigens (Faenia rectivirgula). Results demonstrated that 15% of samples from
      the RAO-affected horses reacted positively in this in vitro bioassay, whereas the
      samples from unaffected horses did not. This bioassay indicates that reaginic
      antibodies could be involved in the immunological mechanism leading to RAO; and
      this technique may facilitate future research in other allergic diseases in
      horses.

PMID- 20814742
TI  - Social value of supported employment for psychosocial program participants.
AB  - Members of a psychiatric psychosocial program designed to provide both supported
      employment and peer support were surveyed about their current social activities,
      sources of social support, and social life improvement since joining the program.
      Survey respondents who worked a mainstream job (n=17) reported greater peer
      contact in community locations, and correspondingly greater social life
      improvement, than those who remained unemployed or worked volunteer jobs (n=45).
      Results of a hierarchical regression analysis (N=62) that explored this positive
      correlation between mainstream work, community-based peer contact, and social
      life satisfaction suggest that working a job in an integrated setting that paid
      at least minimum wage encouraged program participants to meet and interact in
      community locations, thereby strengthening peer mutual support while furthering
      social integration. This unique pattern of findings requires replication, and we
      recommend that other psychosocial programs conduct similar quality improvement
      studies to provide further insights into the relationship between peer support
      and community integration.

PMID- 20814743
TI  - Amorphous manganese-calcium oxides as a possible evolutionary origin for the
      CaMn4 cluster in photosystem II.
AB  - In this paper a few calcium-manganese oxides and calcium-manganese minerals are
      studied as catalysts for water oxidation. The natural mineral marokite is also
      studied as a catalyst for water oxidation for the first time. Marokite is made up
      of edge-sharing Mn(3+) in a distorted octahedral environment and eight-coordinate
      Ca(2+) centered polyhedral layers. The structure is similar to recent models of
      the oxygen evolving complex in photosystem II. Thus, the oxygen evolving complex
      in photosystem II does not have an unusual structure and could be synthesized
      hydrothermally. Also in this paper, oxygen evolution is studied with marokite
      (CaMn2O4), pyrolusite (MnO2) and compared with hollandite
      (Ba(0.2)Ca(0.15)K(0.3)Mn(6.9)Al(0.2)Si(0.3)O(16)), hausmannite (Mn3O4),
      Mn2O3.H2O, Ca Mn3O6.H2O, CaMn4O8.H2O, CaMn2O4.H2O and synthetic marokite
      (CaMn2O4). I propose that the origin of the oxygen evolving complex in
      photosystem II resulted from absorption of calcium and manganese ions that were
      precipitated together in the archean oceans by protocyanobacteria because of
      changing pH from ~5 to ~8-10. As reported in this paper, amorphous calcium
      manganese oxides with different ratios of manganese and calcium are effective
      catalysts for water oxidation. The bond types and lengths of the calcium and
      manganese ions in the calcium-manganese oxides are directly comparable to those
      in the OEC. This primitive structure of these amorphous calcium-manganese
      compounds could be changed and modified by environmental groups (amino acids) to
      form the oxygen evolving complex in photosystem II.

PMID- 20814744
TI  - Opuntia humifusa partitioned extracts inhibit the growth of U87MG human
      glioblastoma cells.
AB  - Opuntia humifusa, a member of the Cactaceae family widely distributed in the
      southern regions of the Korean peninsula, has potential bioactive functions and
      medicinal benefits. In the present study, we investigated the effect of hexane,
      ethyl acetate extracts and water partitioned fraction of O. humifusa on
      proliferation, G1 arrest and apoptosis in U87MG human glioblastoma cells.
      Glioblastoma cellular proliferation was evaluated using the MTT (3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and the effects of
      O. humifusa partitioned extracts on cell cycle and apoptosis were analyzed by
      flow cytometry. Our results revealed that when U87MG cells were treated with
      hexane extracts and water partitioned fraction of O. humifusa, the number of
      viable cells decreased in a concentration-dependent manner. In addition, water
      partitioned fractions of O. humifusa induced G1 arrest and non-apoptotic cell
      death as well as significant increases in ROS production in U87MG cells. In
      conclusion, water partitioned fractions of O. humifusa induce G1 arrest and
      inhibit U87MG human glioblastoma cell proliferation.

PMID- 20814745
TI  - A mesofluidic multiplex immunosensor for detection of circulating cytokeratin
      positive cells in the blood of breast cancer patients.
AB  - We have recently reported the analytical performance of an immunosensor
      comprising one mm-scale parallel plate laminar flow chamber and applied to
      capture MCF7 breast cancer cells (Ehrhart et al., Biosens. Bioelectr. 24, 467,
      2008). Herein we present a new multiplex immunosensor embodying four parallel
      plate laminar flow chambers that fit onto a standard, functionalized, microscopy
      glass slide. The four surfaces are coated with long alkyl chain spacers of 21
      aminohenicosyl trichlorosilane (AHTS) and then grafted with a monoclonal anti
      human epithelial cell adhesion molecule (EpCAM) antibody specific of target cells
      to immobilize. We first demonstrate a significantly (P < 0.01) improved capacity
      of each of the four flow chambers of the multiplex immunosensor to capture MCF7
      cells compared to the previous single chamber device. Second, in addition to an
      increase of cell immobilization, the multiplex device offers a versatile tool
      easily grafted with various purified antibodies onto the four surfaces. Third, we
      obtained high cell capture rate and efficiency of various numbers of MCF7 cells
      spiked in buffer containing an equal number of background leukocytes. And fourth,
      we demonstrate isolation efficiency of circulating tumor cells (CTCs) from
      peripheral blood drawn from a small cohort of patients with localized or
      metastatic breast cancer. This new multiplex immunosensor could be tested for its
      potential to capture different subpopulations of CTCs.

PMID- 20814746
TI  - Comments on: Improving breast cancer surgery: a classification and quadrant per
      quadrant atlas for oncoplastic surgery (Clough KB, Kaufman GJ, et al. ASO DOI
      10.1245/s10434-009-0792-y).

PMID- 20814747
TI  - p21 WAF1 is involved in interferon-beta-induced attenuation of telomerase
      activity and human telomerase reverse transcriptase (hTERT) expression in ovarian
      cancer.
AB  - Telomerase activation is a key step in the development of human cancers.
      Interferon-beta (IFN-beta) signaling induces growth arrest in many tumors but the
      anticancer mechanism of IFN-beta is poorly understood. In the present study, we
      show that IFN-beta signaling represses telomerase activity and human telomerase
      reverse transcriptase (hTERT) transcription in ovarian cancer and suggest that
      this signaling is mediated by p21(WAF1). IFN-beta triggered down-regulation of
      telomerase activity and hTERT mRNA expression and also induced p21 expression,
      independently of p53 induction. Ectopic expression of p21 attenuated hTERT
      promoter activity. Murine embryonic fibroblasts (MEFs) genetically deficient in
      p21 (p21-/-) showed elevated (> 15 times) hTERT promoter activity compared to
      wild-type MEFs. Overexpression of p21 reduced the hTERT promoter activity of p21
      /- MEFs and hTERT mRNA expression in HCT119 p21(WAF1) null cell. These findings
      provide evidence that p21 is a potential mediator of IFN-beta-induced attenuation
      of telomerase activity and tumor suppression.

PMID- 20814748
TI  - The expression profile and function of Satb2 in zebrafish embryonic development.
AB  - The present study shows the expression profile and function of the homeobox gene,
      satb2 during zebrafish embryonic development. Satb2 was ubiquitously expressed
      from the 1 cell stage to the 10-somite stage in zebrafish embryos. Satb2 showed
      stage-specific expression profiles such as in the pronephric duct at 24 hpf, the
      branchial arches at 36 hpf, and the ganglion cell layer of the retina and fins at
      48 hpf. Additionally, satb2 knockdown embryos were arrested at 50-60% epiboly,
      and transplantation experiments with satb2 knockdown cells showed migration
      defects. Interestingly, satb2 knockdown cells also exhibited down-regulation of
      dynamin II and VAMP4, which are involved in exocytosis and endocytosis,
      respectively. Furthermore, satb2 knockdown cells have a disorganized actin
      distribution and an underdeveloped external yolk syncytial layer, both of which
      are involved in epiboly. These results suggest that satb2 has a functional role
      in epiboly. This role may potentially be the regulation of endo-exocytic vesicle
      transport-dependent cell migration and/or the regulation of the development of
      the yolk syncytial layer.

PMID- 20814749
TI  - The neural stem cell fate determinant TLX promotes tumorigenesis and genesis of
      cells resembling glioma stem cells.
AB  - A growing body of evidence indicates that deregulation of stem cell fate
      determinants is a hallmark of many types of malignancies. The neural stem cell
      fate determinant TLX plays a pivotal role in neurogenesis in the adult brain by
      maintaining neural stem cells. Here, we report a tumorigenic role of TLX in brain
      tumor initiation and progression. Increased TLX expression was observed in a
      number of glioma cells and glioma stem cells, and correlated with poor survival
      of patients with gliomas. Ectopic expression of TLX in the U87MG glioma cell line
      and Ink4a/Arf-deficient mouse astrocytes (Ink4a/Arf(-/-) astrocytes) induced cell
      proliferation with a concomitant increase in cyclin D expression, and accelerated
      foci formation in soft agar and tumor formation in in vivo transplantation
      assays. Furthermore, overexpression of TLX in Ink4a/Arf(-/-) astrocytes inhibited
      cell migration and invasion and promoted neurosphere formation and Nestin
      expression, which are hallmark characteristics of glioma stem cells, under stem
      cell culture conditions. Our results indicate that TLX is involved in glioma stem
      cell genesis and represents a potential therapeutic target for this type of
      malignancy.

PMID- 20814750
TI  - Overexpression of ornithine decarboxylase suppresses thapsigargin-induced
      apoptosis.
AB  - Ornithine decarboxylase (ODC), the key enzyme of polyamine biosynthesis, has
      paradoxical roles in apoptosis. Our published papers show overexpression of ODC
      prevents the apoptosis induced by many cytotoxic drugs. Thapsigargin (TG) is an
      inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca(2+) ATPase (SERCA)
      pumps and causes ER stress-induced apoptosis. We used ODC overexpressing cell
      lines to examine whether overexpression of ODC inhibits TG-induced apoptosis. Our
      results indicated overexpression of ODC attenuated TG-induced apoptosis.
      Overexpression of ODC blocked procaspase-4 cleavage and phosphorylation of
      protein kinase-like ER-resident kinase (PERK), triggered by TG. It also
      attenuated the increase in CAAT/enhancer binding protein homologous protein
      (CHOP). Cells with overexpressed ODC had greater Bcl-2 expression. Overexpression
      of ODC preserved the expression of Bcl-2, inhibited the increase in Bak and
      stabilized mitochondrial membrane potential without the influences of TG.
      Cytochrome c release and down-stream caspase activation were blocked. That is,
      overexpression of ODC inhibits the mitochondria-mediated apoptotic pathway,
      induced by TG. Finally, overexpression of ODC maintains the protein and mRNA
      expression of SERCA. In conclusion, overexpression of ODC suppresses TG-induced
      apoptosis by blocking caspase-4 activation and PERK phosphorylation, attenuating
      CHOP expression and inhibiting the mitochondria-mediated apoptotic pathway.

PMID- 20814752
TI  - Seven new dammarane triterpenes from the floral spikes of Betula platyphylla var.
      japonica.
AB  - Seven new dammarane-type triterpenoids, including two 20(S)-hydroxy-25-methoxy
      dammar-23-enes (1 and 2), two 20(S),24(R)-epoxydammaranes (3 and 4), a
      cabralealactone (5), and two 20(S),25-epoxydammaranes (6 and 7), together with
      seven known triterpenes (8-14), were isolated from the floral spikes of Betula
      platyphylla var. japonica. The structures for all compounds were elucidated by
      the analyses of extensive spectroscopic data, as well as chemical examinations.

PMID- 20814751
TI  - Accelerated immune senescence and reduced response to vaccination in
      ovariectomized female rhesus macaques.
AB  - Aging is associated with a general dysregulation in immune function, commonly
      referred to as "immune senescence". Several studies have shown that female sex
      steroids can modulate the immune response. However, the impact of menopause
      associated loss of estrogen and progestins on immune senescence remains poorly
      understood. To help answer this question, we examined the effect of ovariectomy
      on T-cell homeostasis and function in adult and aged female rhesus macaques. Our
      data show that in adult female rhesus macaques, ovariectomy increased the
      frequency of naive CD4 T cells. In contrast, ovariectomized (ovx) aged female
      rhesus macaques had increased frequency of terminally differentiated CD4 effector
      memory T cells and inflammatory cytokine-secreting memory T cells. Moreover,
      ovariectomy reduced the immune response (T-cell cytokine and IgG production)
      following vaccination with modified vaccinia ankara in both adult and aged female
      rhesus macaques compared to ovary-intact age-matched controls. Interestingly,
      hormone therapy (estradiol alone or in conjunction with progesterone) partially
      improved the T-cell response to vaccination in aged ovariectomized female rhesus
      macaques. These data suggest that the loss of ovarian steroids, notably estradiol
      and progesterone, may contribute to reduced immune function in post-menopausal
      women and that hormone therapy may improve immune response to vaccination in this
      growing segment of the population.

PMID- 20814753
TI  - Antiobesity effects of Kaempferia parviflora in spontaneously obese type II
      diabetic mice.
AB  - Kaempferia parviflora Wall. Ex Baker (KP) has been used as a folk medicine in
      Laos and Thailand to lower blood glucose levels, improve blood flow, and increase
      vitality. This study investigated the preventive effects of KP on obesity and its
      downstream symptoms (various metabolic disorders) using Tsumura, Suzuki, Obese
      Diabetes (TSOD) mice, a multifactorial genetic disease animal model in which
      metabolic diseases develop spontaneously, similar to metabolic syndrome in
      humans, and Tsumura, Suzuki, Non-Obesity (TSNO) mice as the corresponding control
      mice. When feed that was mixed with KP (1 or 3%) was given ad libitum to TSOD and
      TSNO mice for 8 weeks, body weight increase, visceral fat accumulation, lipid
      metabolism abnormalities, hyperinsulinemia, glucose intolerance, insulin
      resistance, hypertension, and peripheral neuropathy were suppressed in TSOD mice,
      but no marked differences were observed in TSNO mice. Because KP had preventive
      effects on metabolic diseases, including antiobesity effects, only in obese
      animals, we propose that KP will be extremely valuable as a medicine or component
      of food in alternative health care.

PMID- 20814754
TI  - Prenylated flavonoid glucoside and two aliphatic alcohol glycosides from the
      leaves of Euodia meliaefolia (Hance) Benth.
AB  - A new prenylated flavonoid (1) and two new aliphatic glycosides (2, 3) have been
      isolated from leaves of Euodia meliaefolia (Hance) Benth., together with three
      known compounds, (2R,3R)-5,7,4'-trihydroxy-8-(3-methylbut-2-enyl)dihydroflavonol
      7-O-beta-D: -glucopyranoside (phellamurin) (4), (2R,3R)-dihydroquercetin 3'-O
      beta-D: -glucopyranoside (5), and (7R,8S)-dihydrodiconiferyl alcohol 4-O-beta-D: 
      glucopyranoside (6). Their structures were determined on the basis of the results
      of spectroscopic analysis.

PMID- 20814755
TI  - Effect of Curcuma comosa and estradiol on the spatial memory and hippocampal
      estrogen receptor in the post-training ovariectomized rats.
AB  - Curcuma comosa was reported to have uterotrophic effects in ovariectomized (OVX)
      rats. The present study aims to investigate the plant estrogenic-like effects of
      C. comosa hexane extract on spatial memory and estrogen receptors (ER) in the
      hippocampus. Female rats received 5 days' Morris water maze training before the
      ovariectomy, followed by the daily intraperitoneal administration of C. comosa
      hexane extract at a dose of 250 and 500 mg/kg body weight for 4 weeks. Estradiol
      (10 MUg/kg body weight) was used as the positive control. OVX significantly
      increased the latency of the animal to the platform, while estradiol and both
      doses of C. comosa hexane extract reversed the memory impairments. By using the
      reverse transcription polymerase chain reaction technique, C. comosa hexane
      extract was shown to produce a selective increase of the ER alpha subtype but not
      beta subtype in hippocampus, while estradiol increased both of them. C. comosa
      did not affect spatial memory, learning ability, and ER mRNA levels in the sham
      OVX rats. In conclusion, C. comosa hexane extract improved the spatial memory of
      the OVX rats, which was similar to estrogen. The influence on the memory changes
      might be selectively related to ER alpha in the hippocampus.

PMID- 20814756
TI  - Ginkgo biloba extract enhances glucose tolerance in hyperinsulinism-induced
      hepatic cells.
AB  - Ginkgo biloba, an herbal medication, is capable of lowering glucose, fat, and
      lipid peroxide in diabetic patients. In the current study, we tested the
      hypothesis that Ginkgo biloba extract (GBE) prevented hyperinsulinism-induced
      glucose intolerance in hepatocytes. We investigated the effects of GBE on glucose
      consumption, glucokinase activity, and mRNA levels of key genes in glucose
      metabolism and the insulin signaling pathway. To better show its efficacy, we
      included a control group that was treated with rosiglitazone, a type of
      thiazolidinedione (TZD). The data indicated that GBE repressed glucose uptake
      under normal conditions, while it dramatically improved glucose tolerance under
      insulin-resistant conditions. Furthermore, after analyzing gene expression, we
      suggest that GBE chiefly exerts its effects by stimulating IRS-2 transcription.
      It should be noted that, unlike rosiglitazone, GBE did not stimulate excessive
      glucose uptake as it improved glucose tolerance. It is said that GBE treatment
      could avoid drug-induced obesity. Our data suggest that GBE has the potential to
      prevent insulin resistance and is a promising anti-diabetic drug.

PMID- 20814757
TI  - Relationships of land use mix with walking for transport: do land uses and
      geographical scale matter?
AB  - Physical activity and public health recommendations now emphasize the creation of
      activity-friendly neighborhoods. Mixed land use in a neighborhood is important in
      this regard, as it reflects the availability of destinations to which residents
      can walk or ride bicycles, and thus is likely to contribute to residents' active
      lifestyles that in turn will influence their overall health. Relationships
      between land use mix (LUM) and physical activity have not been apparent in some
      studies, which may be because geographical scale and the specificity of
      hypothesized environment-behavior associations are not taken into account. We
      compared the strength of association of four Geographic Information Systems
      derived LUM measures with walking for transport and perceived proximity to
      destinations. We assessed physical activity behaviors of 2,506 adults in 154
      Census Collection Districts (CCDs) in Adelaide, Australia, for which ''original''
      LUM measures were calculated, and then refined by either: accounting for the
      geographic scale of measurement; including only the most-relevant land uses; or,
      both. The refined (but not the ''original'') LUM measures had significant
      associations with the frequency of walking for transport (p < 0.05) and area
      corrected measures had significant associations with the duration of walking for
      transport. All LUM measures had significant associations with perceived proximity
      to destinations, but stronger associations were seen when using the refined
      measures compared with the original LUM. Identifying the LUM attributes most
      strongly associated with walking for transport is a priority and can inform
      environmental and policy initiatives that are needed to promote health-enhancing
      physical activity.

PMID- 20814758
TI  - Boundary estimation of fiber bundles derived from diffusion tensor images.
AB  - PURPOSE: Diffusion tensor imaging (DTI) is a non-invasive imaging technique that
      allows estimating the location of white matter tracts based on the measurement of
      water diffusion properties. Using DTI data, the fiber bundle boundary can be
      determined to gain information about eloquent structures, which is of major
      interest for neurosurgical interventions. In this paper, a novel approach for
      boundary estimation is presented. METHODS: DTI in combination with diverse
      segmentation algorithms allows estimating the position and course of fiber tracts
      in the human brain. For additional information about the expansion of the fiber
      bundle, the introduced iterative approach uses the centerline of a tracked fiber
      bundle between two regions of interest (ROI). After sampling along this
      centerline, rays are sent out radially, discrete 2D contours are calculated, and
      the fiber bundle boundary is estimated in a stepwise manner. For this purpose,
      each ray is analyzed using several criteria, including anisotropy parameters and
      angle parameters, to find the boundary point. RESULTS: The novel method for
      automatically calculating the boundaries has been applied to several artificially
      generated DTI datasets. Multiple parameters were varied: number of rays per
      plane, sampling rate and sampled points along the rays. For the DTI data used in
      the experiments, the method yielded a dice similarity coefficient (DSC) between
      74.7 and 91.5%. CONCLUSIONS: In this paper, a novel approach to retrieve
      significant information about the fiber bundle boundary from DTI data is
      presented. The method is a contribution to gather important knowledge about high
      risk structures in neurosurgical interventions.

PMID- 20814760
TI  - Determinants of hyperhomocysteinemia after gastric bypass surgery in obese
      subjects.
AB  - BACKGROUND: Effectiveness of gastric bypass (GBP) on reduction of vascular risk
      factors is well established, but GBP induces nutritional deficits that could
      reduce the cardiovascular benefit of weight loss. Particularly,
      hyperhomocysteinemia, now clearly identified as a vascular risk factor, has been
      described after GBP. The aim of this study was to clarify the factors associated
      with increased homocysteine concentration after GBP. METHODS: Homocysteine
      concentration and multiple nutritional parameters were measured in 213
      consecutive subjects. One hundred and eight subjects were studied before surgery
      (control (CT)), 115 one to 6 years after GBP, and 41 both before and 6 months
      after GBP. RESULTS: Homocysteine concentration did not differ before and after
      GBP (9.1 +/- 3.2 vs 8.6 +/- 3.4 MUmol/l), but 94% of subjects had been
      supplemented with a multivitamin preparation after surgery. The nutritional
      parameters best correlated with homocysteine concentration both before and after
      GBP were folate and creatinine concentrations (p < 0.0001). In contrast, vitamin
      B12 and metabolic parameters (including glucose, insulin, lipids and C-reactive
      protein) were not associated with homocysteine concentration. After GBP,
      homocysteine concentration was significantly lower in subjects taking a
      multivitamin supplementation containing a high dose of folate than those who did
      not (7.7 +/- 2.8 vs 10.1 +/- 3.9 MUmol/l, p < 0.0001). CONCLUSIONS: The main
      determinants of homocysteine concentration identified in this study are folate
      and serum creatinine. Multivitamin supplementation with a high dose of folate
      prevents hyperhomocysteinemia after GBP.

PMID- 20814761
TI  - The OTSC(r)-clip in revisional endoscopy against weight gain after bariatric
      gastric bypass surgery.
AB  - The maintenance of the restrictive component of the Fobi pouch gastric bypass is
      essential for permanent weight control. Dilatation of the pouch-outlet and of the
      pouch itself is responsible for substantial weight gain by an increased volume
      per meal and binge-eating due to the rapid emptying. An endoscopic over-the-scope
      clip (OTSC(r); Ovesco AG, Tubingen, Germany) was applied in 94 patients following
      gastric bypass and unintended weight gain by dilated gastro-jejunostomy to narrow
      the pouch-outlet. The OTSC(r)-clip application was safe and efficient to reduce
      the pouch-outlet in all cases. Best clinical results were obtained by narrowing
      the gastro-jejunostomy by placing two clips at opposite sites, hence reducing the
      outlet of more than 80%. Preferably, the clip approximated the whole thickness of
      the wall to avoid further dilatation of the anastomosis. Between surgery and
      OTSC(r)-clip application the mean BMI dropped from 45.8 (+/-3.6) to 32.8 (+/
      1.9). At the first follow-up about 3 months (mean 118 days, +/-46 days) after
      OTSC(r)-clip application the mean BMI was 29.7 (+/-1.8). At the second follow-up
      about 1 year (mean 352 days, +/-66 days) after OTSC(r)-clip application the mean
      BMI was 27.4 (+/-3.8). The OTSC(r)-clip for revisional endoscopy after gastric
      bypass is reliable and effective in treating weight gain due to a dilated pouch
      outlet with favorable short- and midterm results.

PMID- 20814762
TI  - Clear cell carcinoid of the appendix: an uncommon variant of lipid-rich
      neuroendocrine tumor with a broad differential diagnosis.
AB  - The designation of clear cell/lipid-rich refers to an unusual variant of
      neuroendocrine tumor ("carcinoid") described in several organs, but only recently
      observed in the appendix. In this study, we report the morphologic,
      immunohistochemical, and ultrastructural features of an incidentally discovered
      appendiceal clear cell/lipid-rich carcinoid in a 32-year-old man without any
      evidence of von Hippel-Lindau disease. Differential diagnosis with mimicking
      neoplastic and non-tumor lesions, epidemiology, and clinical behavior of this
      exceedingly rare variant of carcinoid of the appendix are also discussed.

PMID- 20814763
TI  - Treatment for non-dysplastic Barrett's oesophagus: a well-informed, demanding
      patient.

PMID- 20814764
TI  - Stereotactic radiosurgery alone for patients with 1-4 radioresistant brain
      metastases.
AB  - Brain metastases from radioresistant histologies are perceived to be less
      responsive to WBRT compared to other histologies, and stereotactic radiosurgery
      (SRS) may provide better local control. The aim of this study was to examine the
      outcomes of patients with 1-4 brain metastasis from radioresistant histologies
      (renal cell carcinoma and melanoma) treated with SRS alone. Thirty-eight patients
      with 1-4 radioresistant brain metastases (66 lesions) were treated with SRS
      alone. The median age was 55 years. Fourteen and 24 patients had renal cell
      carcinoma (RCC) and melanoma brain metastases, respectively. Distribution of
      number of lesions was as follows: one lesion, 22 patients; 2 lesions, 8 patients;
      3 lesions, 5 patients; and 4 lesions, 3 patients. Distribution of RTOG recursive
      partitioning analysis (RPA) classes was as follows: II, 37 patients and III, 1
      patient. The median marginal dose was 20 Gy. The median follow-up was 6.1 months.
      The 3-, 6-, 9-, 12-, and 18-month local control (LC) rates were 87.9, 81.4, 67.9,
      67.9, and 60.3%, respectively. The corresponding free-from-distant-brain failure
      (FFDBF) rates were 71.3, 58.1, 49.8, 40.2, and 27.6%. The corresponding
      progression-free survival (PFS) rates were 55.3, 41.9, 33, 23.3, and 13.3%. RCC
      histology was associated with better LC (P = 0.0055). Although SRS alone could
      yield reasonable LC in patients with 1-4 radioresistant brain metastases, the
      risk of distant brain failure was substantial. The approach of routine omission
      of WBRT outside of a trial setting should be used judiciously.

PMID- 20814765
TI  - Alcohol and HIV disease progression: weighing the evidence.
AB  - Heavy alcohol use is commonplace among HIV-infected individuals; however, the
      extent that alcohol use adversely impacts HIV disease progression has not been
      fully elucidated. Fairly strong evidence suggests that heavy alcohol consumption
      results in behavioral and biological processes that likely increase HIV disease
      progression, and experimental evidence of the biological effect of heavy alcohol
      on simian immunodeficiency virus in macaques is quite suggestive. However,
      several observational studies of the effect of heavy alcohol consumption on HIV
      progression conducted in the 1990s found no association of heavy alcohol
      consumption with time to AIDS diagnosis, while some more recent studies showed
      associations of heavy alcohol consumption with declines of CD4 cell counts and
      nonsuppression of HIV viral load. We discuss several plausible biological and
      behavioral mechanisms by which alcohol may cause HIV disease progression,
      evidence from prospective observational human studies, and suggest future
      research to further illuminate this important issue.

PMID- 20814767
TI  - Complete 1H, 13C and 15N NMR assignments for donor-strand complemented AafA, the
      major pilin of aggregative adherence fimbriae (AAF/II) from enteroaggregative E.
      coli.
AB  - Aggregative adherence fimbriae (AAF) are the primary adhesive factors of
      enteroaggregative Escherichia coli (EAEC) and are required for intestinal
      colonization. They mediate binding to extracellular matrix proteins of the
      enteric mucosa and display proinflammatory effects on epithelial cells in vitro.
      Among the simplest of bacterial fimbriae, these passive hairlike appendages are
      composed primarily of a single 16-kDa structural and adhesive subunit, AafA.
      Oligomerization occurs by incorporating the N-terminal strand of each AafA
      subunit into an otherwise incomplete beta-sheet of an adjacent AafA subunit. We
      have engineered a highly soluble AafA monomer by positioning the N-terminal
      "donor strand" at the C-terminus, following a turn and short linker that were
      introduced to allow access of the donor strand to the recipient cleft of the same
      subunit. The resulting "donor-strand complemented" AafA subunit, or AafA-dsc
      folds autonomously, is monodisperse in solution, and yields high quality NMR
      spectral data. Here, we report the (1)H, (13)C, and (15)N chemical shift
      assignments for AafA-dsc.

PMID- 20814766
TI  - Alpha-linolenic acid: is it essential to cardiovascular health?
AB  - There is a large body of scientific evidence that has been confirmed in
      randomized controlled trials indicating a cardioprotective effect for omega-3
      fatty acids from fish. For alpha-linolenic acid (ALA), which is the omega-3 fatty
      acid from plants, the relation to cardiovascular health is less clear. We
      reviewed the recent literature on dietary ALA intake, ALA tissue concentrations,
      and cardiovascular health in humans. Short-term trials (6-12 weeks) in generally
      healthy participants mostly showed no or inconsistent effects of ALA intake (1.2
      3.6 g/d) on blood lipids, low-density lipoprotein oxidation, lipoprotein(a), and
      apolipoproteins A-I and B. Studies of ALA in relation to inflammatory markers and
      glucose metabolism yielded conflicting results. With regard to clinical
      cardiovascular outcomes, there is observational evidence for a protective effect
      against nonfatal myocardial infarction. However, no protective associations were
      observed between ALA status and risk of heart failure, atrial fibrillation, and
      sudden death. Findings from long-term trials of ALA supplementation are awaited
      to answer the question whether food-based or higher doses of ALA could be
      important for cardiovascular health in cardiac patients and the general
      population.

PMID- 20814768
TI  - Predicting individual differences in reading comprehension: a twin study.
AB  - We examined the Simple View of reading from a behavioral genetic perspective. Two
      aspects of word decoding (phonological decoding and word recognition), two
      aspects of oral language skill (listening comprehension and vocabulary), and
      reading comprehension were assessed in a twin sample at age 9. Using latent
      factor models, we found that overlap among phonological decoding, word
      recognition, listening comprehension, vocabulary, and reading comprehension was
      primarily due to genetic influences. Shared environmental influences accounted
      for associations among word recognition, listening comprehension, vocabulary, and
      reading comprehension. Independent of phonological decoding and word recognition,
      there was a separate genetic link between listening comprehension, vocabulary,
      and reading comprehension and a specific shared environmental link between
      vocabulary and reading comprehension. There were no residual genetic or
      environmental influences on reading comprehension. The findings provide evidence
      for a genetic basis to the "Simple View" of reading.

PMID- 20814770
TI  - Estimation of anxiety and depression in patients with early stage breast cancer
      before and after radiation therapy.
AB  - BACKGROUND: Most previous studies about anxiety and depression in patients
      undergoing radiotherapy have only measured the quantity of general depression and
      anxiety and have not studied specific periods of involvement. The aim of this
      study was to assess anxiety and depression among early breast cancer patients,
      and the anxiety experienced immediately before and after radiotherapy. METHODS:
      Women who started radiotherapy for stage I or II breast cancer (n = 172) were
      asked to answer two questionnaires: the Hospital Anxiety and Depression Scale
      (HADS) and Radiotherapy Categorical Anxiety Scale immediately before and after
      radiation therapy. RESULTS: The results showed that the mean scores of anxiety
      and depression (HADS and Radiotherapy Categorical Anxiety Scale) decreased after
      radiotherapy. The mean score of depression (HAD-D) in the group receiving
      conventional radiotherapy was higher than in those receiving hypofractionated
      radiotherapy before and after radiotherapy. The mean scores of anxiety and
      depression (HADS) in the endocrine therapy group were lower than in the group
      without endocrine therapy before treatment. However, the scores after treatment
      of both groups were not significant. CONCLUSION: Some intervention may be needed
      to decrease the temporary anxiety and depression raised during radiotherapy for
      early stage breast cancer patients. This is especially so for patients who do not
      receive concurrent endocrine therapy and choose the conventional radiotherapy
      course.

PMID- 20814769
TI  - The skeletal subsystem as an integrative physiology paradigm.
AB  - Homeostatic bone remodeling depends on precise regulation of osteoblast
      osteoclast coupling through intricate endocrine, immune, neuronal, and mechanical
      factors. The osteoblast-osteoclast model of bone physiology with layers of
      regulatory complexity can be investigated as a component of a local skeletal
      subsystem or as a part of a complete whole-body system. In this review, we flip
      the traditional investigative paradigm of scientific experimentation ("bottom-top
      research") to a "top-bottom" approach using systems biology. We first establish
      the intricacies of the two-cell model at the molecular signaling level. We then
      provide, on a systems level, an integrative physiologic approach involving many
      recognized organ-level subsystems having direct and/or indirect effects on bone
      remodeling. Lastly, a hypothetical model of bone remodeling based on frequency
      and amplitude regulatory mechanisms is presented. It is hoped that by providing a
      thorough model of skeletal homeostasis, future progress can be made in
      researching and treating skeletal morbidities.

PMID- 20814771
TI  - Bilateral necrotizing fasciitis of the breast following quadrantectomy.
AB  - Necrotizing fasciitis (NF) is a rare and highly lethal soft-tissue infection that
      involves the skin, subcutaneous tissue, and fascia. Although it can affect any
      part of the body, the breast is seldom involved. We describe a case of bilateral
      NF of the breast following elective quadrantectomy, successfully treated with
      antibiotics, bilateral mastectomy, and a vacuum-assisted wound closure system. 

PMID- 20814772
TI  - What is the evidence for total knee arthroplasty in young patients?: a systematic
      review of the literature.
AB  - BACKGROUND: TKA is commonly performed to treat advanced inflammatory and
      degenerative knee arthritis. With increasing use in younger patients, it is
      important to define the best practices to enhance clinical performance and
      implant longevity. QUESTIONS/PURPOSES: We systematically reviewed the literature
      to assess: (1) how TKAs perform in young patients; (2) whether the TKA is a
      durable procedure for young patients, and (3) what guidance the literature
      outlines for TKA in young patients. METHODS: We searched the literature between
      1950 and 2009 for all studies reporting on TKAs for patients younger than 55
      years that documented clinical and radiographic assessments with a minimum 2-year
      followup. Thirteen studies, reporting on 908 TKAs performed for 671 patients, met
      these criteria. RESULTS: Mean Knee Society clinical and functional scores
      increased by 47 and 37 points, respectively. Implant survivorship was reported
      between 90.6% and 99% during the first decade and between 85% and 96.5% during
      the second decade of followup. The literature does not direct specific techniques
      for TKA for young patients. CONCLUSIONS: TKA provides surgeon-measured clinical
      and functional improvements with a moderate increase in second-decade implant
      failures. Improvements in study design and reporting will be beneficial to guide
      decisions regarding implant selection and surgical technique. LEVEL OF EVIDENCE:
      Level IV, therapeutic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 20814774
TI  - Bleeding due to slippage of elastic band during variceal ligation: successful use
      of Ankaferd blood stopper.
AB  - Ankaferd blood stopper (ABS) is a hemostatic agent that induces clot formation by
      a special protein network which mainly causes powerful erythrocyte aggregation.
      The use of topical ABS as a hemostatic agent has been approved in Turkey for the
      management of dermal, external post-surgical and post-dental surgery bleeding.
      ABS has been successfully used in Dieulafoy lesion and bleeding from
      gastrointestinal neoplasms. We present a patient with alcoholic cirrhosis who
      developed severe bleeding during an elective endoscopic variceal ligation (EVL)
      session due to immediate band slippage, in whom endoscopic topical application of
      ABS was associated with cessation of bleeding. The major advantages of ABS appear
      to be ease of use and lack of side effect.

PMID- 20814773
TI  - In vivo normal knee kinematics: is ethnicity or gender an influencing factor?
AB  - BACKGROUND: In vivo studies have suggested Caucasians achieve lower average knee
      flexion than non-Western populations. Some previous studies have also suggested
      gender may influence condylar AP translation and axial rotation, while others
      report an absence of such an influence. QUESTIONS/PURPOSES: We determined whether
      different ethnic and gender groups residing in the United States had different
      knee translations and rotations. METHODS: Three-dimensional knee rotations and
      translations were determined for 72 healthy subjects (24 Caucasian men, 24
      Caucasian women, 13 Japanese men, 11 Japanese women) from full extension to
      maximum flexion using a fluoroscopic technique, under in vivo, weightbearing
      conditions. RESULTS: Although we observed substantial variability in all groups,
      small differences between groups were found, especially in deep flexion. Japanese
      women and men and Caucasian women achieved higher maximum flexion (153 degrees ,
      151 degrees , and 152 degrees , respectively) than Caucasian men (146 degrees ).
      External rotation was higher for these three groups than for Caucasian men. The
      medial condyle remained more anterior for Caucasian women and all Japanese
      subjects than for Caucasian men, possibly leading to greater axial rotation and
      flexion, observed for these three groups. CONCLUSION: We identified small
      differences in maximum flexion between genders and ethnic groups. While no
      differences were identified in the lateral condyle translation, the medial
      condyle remained more stationary and more anterior for the groups that achieved
      highest (and similar) maximum flexion. Therefore, it may be important for future
      implant designs to incorporate these characteristics, such that only the lateral
      condyle experiences greater posterior femoral rollback, while the medial condyle
      remains more stationary throughout flexion.

PMID- 20814775
TI  - Polymerase chain reaction confirmation of diagnosis of intestinal amebiasis in
      Puducherry.
AB  - BACKGROUND: Stool microscopy, the commonly used test for diagnosis of intestinal
      amebiasis, is unreliable as it does not differentiate Entamoeba histolytica, the
      causative agent for amebiasis, from non-pathogenic Entamoeba dispar and Entamoeba
      moshkovskii. METHODS: Two hundred and forty-six stool samples collected between
      January to February 2009, were examined microscopically for E. histolytica/E.
      dispar/E. moshkovskii complex cysts and trophozoites. Nested multiplex PCR
      targeting a 16 S-like rRNA gene for differential detection of all the three
      morphologically similar forms of E. histolytica, E. moshkovskii and E. dispar
      simultaneously was done on all microscopy positive stool samples. RESULTS: Forty
      nine stool samples were positive for Entamoeba spp. by microscopy. Nested
      multiplex PCR for E. histolytica, E. moshkovskii and E. dispar was positive in
      only 19 of these samples, and only 6 of the 19 samples were positive for E.
      histolytica. CONCLUSION: Stool microscopy grossly over-diagnosed intestinal
      amebiasis and is likely to result in unnecessary treatment with anti-protozoal
      drugs.

PMID- 20814776
TI  - [Stability and durability].

PMID- 20814777
TI  - [Early melanoma as opposed to a benign nevus, nevus-associated melanoma, or halo
      nevus with regression?].
AB  - A 43-year-old woman, in whom a melanoma associated with a melanocytic nevus had
      been removed 2 years previously, came for a follow-up examination presenting with
      two light brown to medium brown maculae measuring approximately 7x5 mm with a
      flat papular center. One of the lesions was surrounded by a large white halo
      about 2 mm in size. The differential diagnosis on clinical grounds included a
      halo nevus with a second common nevus, a nevus with regression, and a melanoma
      associated with a nevus. Under the dermatoscope, an unremarkable
      homogeneous/reticular pattern could be seen and in one portion hallmarks of
      regression, namely gray tones and distinct gray-black dots. The diagnosis based
      on histopathological analysis was that of an atypical congenital nevus with
      regression.

PMID- 20814778
TI  - [Andrology].
AB  - Andrology deals with male infertility, erectile dysfunction, loss of libido,
      ejaculatory disorders, hypogonadism, delayed puberty, male contraception,
      gynecomastia and aspects of the aging male. New trends in reproductive medicine
      have influenced the evaluation of andrological patients in recent years. Even
      loss of ejaculated spermatozoa does not necessarily exclude paternity since
      testicular sperm extraction has been established in men with obstructive or non
      obstructive azoospermia. The most important new aspect in andrology is the
      publication of the World Health Organization laboratory manual for semen analysis
      in 2010. Dramatic changes concerning sperm motility and morphology must now be
      considered for the interpretation of standard semen parameters.

PMID- 20814780
TI  - [Limited portal carpal tunnel release. An alternative to classic open release?].
AB  - The aim of this study was to determine the significance of limited portal carpal
      tunnel release compared to the classic open approach. We present a retrospective
      comparative clinical trial including 161 patients (105 open release and 56
      limited portal release). Special interest was directed towards postoperative
      functionality, disorders and quality of life. Significant advantages could be
      demonstrated for the limited portal carpal tunnel release: rapid ability to
      return to work as well as to routine tasks of daily living and high patient
      satisfaction. In the hands of trained surgeons, limited portal carpal tunnel
      release represents a rewarding alternative to the classic open release.

PMID- 20814781
TI  - Effects of acute pramipexole on preference for gambling-like schedules of
      reinforcement in rats.
AB  - RATIONALE: Pramipexole and other direct dopamine agonist medications have been
      implicated in the development of impulsive behavior such as pathological gambling
      among those taking the drug to control symptoms of Parkinson's disease or
      restless leg syndrome. Few laboratory studies examining pramipexole's effects on
      gambling-like behavior have been conducted. OBJECTIVES: The present study used a
      rodent model approximating some aspects of human gambling to examine within
      subject effects of acute pramipexole (0.03, 0.1, 0.18, and 0.3 mg/kg) on rat's
      choices to earn food reinforcement by completing variable-ratio (VR; i.e.,
      gambling-like) or fixed-ratio (FR) response requirements. RESULTS: In a condition
      in which the VR alternative was rarely selected, all but the lowest dose of
      pramipexole significantly increased choice of the VR alternative (an average of
      15% above saline). The same doses did not affect choice significantly in a
      control condition designed to evaluate the involvement of nonspecific drug
      effects. Pramipexole increased latencies to initiate trials (+9.12 s) and to
      begin response runs on forced-choice trials (VR = +0.21 s; FR = +0.88 s), but did
      not affect measures of response perseveration (conditional probabilities of
      "staying"). CONCLUSIONS: The findings are consistent with clinical reports
      linking pramipexole to the expression of increased gambling in humans. Results
      are discussed in the context of neurobehavioral evidence suggesting that dopamine
      agonists increase sensitivity to reward delay and disrupt appropriate feedback
      from negative outcomes.

PMID- 20814782
TI  - Blockade of nucleus accumbens 5-HT2A and 5-HT2C receptors prevents the expression
      of cocaine-induced behavioral and neurochemical sensitization in rats.
AB  - RATIONALE: The serotonin 5-HT(2A) and 5-HT(2C) receptors regulate the capacity of
      acute cocaine to augment behavior and monoamine levels within the nucleus
      accumbens (NAC), a brain region involved in cocaine's addictive and psychotogenic
      properties. OBJECTIVES: In the present study, we tested the hypothesis that NAC 5
      HT(2A) and 5-HT(2C) receptor activation is involved in the expression of cocaine
      induced neuroplasticity following protracted withdrawal from a sensitizing
      repeated cocaine regimen (days 1 and 7, 15 mg/kg; days 2-6, 30 mg/kg, i.p.).
      METHODS: The effects of intra-NAC infusions of the 5-HT(2A) antagonist R-(+)
      alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine methanol
      (MDL 100907; 0, 50, 100, 500 nM) or the 5-HT(2C) antagonist [6-chloro-5-methyl-1
      (6-(2-methylpiridin-3-yloxy)pyridine-3-yl carbamoyl] inodoline dihydrochloride
      (SB 242084; 0, 50, 100, 500 nM) were first assessed upon the expression of
      locomotor activity elicited by a 15-mg/kg cocaine challenge injection
      administered at 3-week withdrawal. A follow-up in vivo microdialysis experiment
      then compared the effects of the local perfusion of 0, 50, or 100 nM of each
      antagonist upon cocaine-induced dopamine and glutamate sensitization in the NAC.
      RESULTS: Although neither MDL 100907 nor SB 242084 altered acute cocaine-induced
      locomotion, SB 242084 reduced acute cocaine-elevated NAC dopamine and glutamate
      levels. Intra-NAC perfusion with either compound blocked the expression of
      cocaine-induced locomotor and glutamate sensitization, but only MDL 100907
      pretreatment prevented the expression of cocaine-induced dopamine sensitization.
      CONCLUSIONS: These data provide the first evidence that NAC 5-HT(2A) and 5-HT(2C)
      receptors are critical for the expression of cocaine-induced neuroplasticity
      following protracted withdrawal, which has relevance for their therapeutic
      utility in the treatment of addiction.

PMID- 20814783
TI  - Refractory idiopathic ventricular tachycardia in a newborn treated successfully
      with phenytoin: old therapies are still effective in the current era.

PMID- 20814784
TI  - Age-related clinical characteristics of isolated congenital unilateral absence of
      a pulmonary artery.
AB  - Unilateral absence of a pulmonary artery (UAPA) is a rare anomaly. Although UAPA
      has been reported previously, its age-related pathogenesis and symptoms remain
      unclear. This retrospective cohort study included cases of UAPA reported in Japan
      at medical meetings or in the literature from 1990 through 2009. Patients with
      other congenital cardiac defects were excluded from the study. Clinical status
      was assessed according to age, and the clinical course of patients with isolated
      UAPA was compared with that of patients who had UAPA with a patent ductus
      arteriosus (PDA). Of the 92 patients with UAPA identified, 78 had isolated UAPA
      (14 with PDA). Hemoptysis and collateral arteries were observed in 0 and 13% of
      patients with isolated UAPA who were younger than 1 year, as compared with 24 and
      50% of those 20 years of age or older, respectively. Pulmonary hypertension was
      present in 5% of the patients aged 1 to 19 years. Among patients 20 years or
      older, however, 32% had pulmonary hypertension, and 8% died. Compared with
      isolated UAPA, UAPA with PDA was associated with an earlier diagnosis (median
      age, 20 vs. 0 years; p = 0.002), a higher prevalence of pulmonary hypertension
      (22% vs. 86%; p < 0.0001), and a higher mortality rate (4% vs. 21%; p = 0.046).
      Collateral artery formation and pulmonary hypertension progress with age in
      patients with UAPA. Early diagnosis and revascularization may prevent the age
      related progression of UAPA.

PMID- 20814785
TI  - Effects of remifentanil anesthesia on cardiac electrophysiologic properties in
      children undergoing catheter ablation of supraventricular tachycardia.
AB  - Remifentanil is commonly used during anesthesia in pediatric electrophysiologic
      studies (EPS). The purpose of this study is to determine the effects of
      remifentanil on the cardiac electrophysiologic properties of children undergoing
      ablation of supraventricular tachycardia (SVT). A prospective study was performed
      in patients undergoing EPS before ablation of SVT. Each patient received two
      different anesthetic protocols: protocol 1 = propofol (200 mcg/kg/min) and
      protocol 2 = propofol (120 mcg/kg/min) plus remifentanil (0.3 mcg/kg/min). EPS
      data were measured during the steady state of each protocol. Paired Student t
      test was performed for analysis of continuous data. All p values <0.05 were
      considered statistically significant. Fifteen patients were enrolled between
      April 2005 and January 2006. The mean age was 13.3 +/- 2.9 years (range 6.7 to
      17.7). Seven patients had atrioventricular (AV) nodal re-entry tachycardia; 5
      patients had Wolff-Parkinson-White syndrome; 2 patients had a concealed accessory
      pathway; and 1 patient was not inducible. Of the 14 patients who underwent
      ablation, 13 (93%) achieved successful. The baseline sinus cycle length extended
      from 884 +/- 141 ms during protocol 1 to 980 +/- 165 ms during protocol 2 (p =
      0.01), and the Wenckebach cycle length lengthened from 377 +/- 96 ms to 406 +/-
      109 ms (p = 0.01). No other variables measured (atrial-His (AH) and His
      ventricular (HV) interval, atrioventricular node (AVN), and atrial, ventricular,
      and accessory pathway effective refractory periods) changed significantly between
      the two different protocols. In pediatric patients undergoing EPS before ablation
      of SVT, remifentanil appears to slow both sinus and AV nodal function. These
      effects should be taken into consideration when performing EPS.

PMID- 20814786
TI  - In vivo precision of a depth-specific topographic mapping technique in the CT
      analysis of osteoarthritic and normal proximal tibial subchondral bone density.
AB  - OBJECTIVE: To test the in vivo precision of a depth-specific topographic mapping
      technique (CT-TOMASD, computed tomography topographic mapping of subchondral
      density) for the 3D assessment of subchondral cortical and trabecular bone
      density in normal and osteoarthritic (OA) human tibiae. METHODS: Fourteen
      participants were recruited (3 men:11 women; mean age: 49.9, SD: 11.9 years) and
      categorized as normal (n = 7) or OA (n = 7). Each participant was scanned using
      clinical quantitative CT (QCT) three times over 2 days. We assessed average
      subchondral bone mineral density (BMD) across three layers (0-2.5 mm, 2.5-5 mm
      and 5-10 mm) measured in relation to depth from the subchondral surface. Regional
      analyses included: medial plateau BMD; lateral plateau BMD;
      anterior/central/posterior compartment BMD; medial:lateral (M:L) BMD ratio; and
      average BMD of a 10-mm diameter "focal spot," which searched each medial and
      lateral plateau for the highest focal densities present within each plateau.
      Precision was assessed using root mean square coefficients of variation
      (CV%(RMS)) and intraclass correlation coefficients (ICC). RESULTS: Average
      CV%(RMS) precision errors for BMD measures were 2.3%, reaching a maximum CV%(RMS)
      of 3.9%. ICC showed high repeatability above 0.98. CONCLUSIONS: CT-TOMASD offered
      precise 3D measures of subchondral BMD. This method has the potential to identify
      and quantify changes in subchondral BMD associated with OA in vivo.

PMID- 20814788
TI  - Safe and effective one-session fractional skin resurfacing using a carbon dioxide
      laser device in super-pulse mode: a clinical and histologic study.
AB  - Carbon dioxide (CO(2)) laser ablative fractional resurfacing produces skin
      damage, with removal of the epidermis and variable portions of the dermis as well
      as associated residual heating, resulting in new collagen formation and skin
      tightening. The nonresurfaced epidermis helps tissue to heal rapidly, with short
      term postoperative erythema. The results for 40 patients (8 men and 32 women)
      after a single session of a fractional CO(2) resurfacing mode were studied. The
      treatments included resurfacing of the full face, periocular upper lip, and
      residual acne scars. The patients had skin prototypes 2 to 4 and wrinkle degrees
      1 to 3. The histologic effects, efficacy, and treatment safety in various
      clinical conditions and for different phototypes are discussed. The CO(2) laser
      for fractional treatment is used in super-pulse mode. The beam is split by a lens
      into several microbeams, and super-pulse repetition is limited by the pulse
      width. The laser needs a power adaptation to meet the set fluence per microbeam.
      Laser pulsing can operate repeatedly on the same spot or be moved randomly over
      the skin, using several passes to achieve a desired residual thermal effect. Low,
      medium, and high settings are preprogrammed in the device, and they indicate the
      strength of resurfacing. A single treatment was given with the patient under
      topical anesthesia. However, the anesthesia was injected on areas of scar tissue.
      Medium settings (2 Hz, 30 W, 60 mJ) were used, and two passes were made for dark
      skins and degree 1 wrinkles. High settings (2 Hz, 60 W, 120 mJ) were used, and
      three passes were made for degree 3 wrinkles and scar tissue. Postoperatively,
      resurfaced areas were treated with an ointment of gentamycin, Retinol Palmitate,
      and DL-methionine (Novartis; Farmaceutics, S.A., Barcelona, Spain). Once
      epithelialization was achieved, antipigment and sun protection agents were
      recommended. Evaluations were performed 15 days and 2 months after treatment by
      both patients and clinicians. Treatment improved wrinkle aspect and scar
      condition, and no patient reported adverse effects or complications, irrespective
      of skin type, except for plaques of erythema in areas that received extra laser
      passes, which were not seen at the 2-month assessment. The results evaluated by
      clinicians were very much in correlation with those of patients. Immediately
      after treatment, vaporization was produced by stacked pulses, with clear ablation
      and collateral heat coagulation. An increased number of random pulses removed
      more epidermis, and with denser pulses per area, a thermal deposit was noted
      histologically. At 2 months, a thicker, multicelluar epidermis and an evident
      increase in collagen were observed. Fractional CO(2) laser permits a variety of
      resurfacing settings that obtain safe, effective skin rejuvenation and correct
      scar tissue in a single treatment.

PMID- 20814789
TI  - The small-molecule tyrosine kinase inhibitor nilotinib is a potent noncompetitive
      inhibitor of the SN-38 glucuronidation by human UGT1A1.
AB  - PURPOSE: Inhibition of the UDP-glucuronosyltransferase (UGT) 1A1 by nilotinib was
      examined in vitro with SN-38 as a substrate, to estimate the possibility of drug
      drug interaction of nilotinib with other medicines predominantly detoxified by
      UGT1A1. METHODS: Inhibition of UGT1A1-catalyzed SN-38 glucuronidation by
      nilotinib was examined with human liver microsomes (HLM) and recombinant human
      UGT1A1 as enzyme sources. Inhibition constants (K(i)) were estimated with kinetic
      analysis. RESULTS: Nilotinib potently inhibited the SN-38 glucuronidation by
      human liver microsomal UGT1A1 and recombinant UGT1A1 in a noncompetitive manner,
      with K(i) values of 0.286 +/- 0.0094 and 0.079 +/- 0.0029 MUM, respectively. If a
      drug that serves as a substrate of UGT1A1 is administered with nilotinib, the
      area under the plasma concentration-time curve of a drug estimated by using these
      K(i) values would be two times or higher than that without nilotinib, suggesting
      drug-drug interactions involving UGT1A1. These in vitro data and the prediction
      of drug-drug interaction are helpful for the clinical management of the nilotinib
      use. CONCLUSION: We found that nilotinib is a potent noncompetitive inhibitor of
      human UGT1A1 activity.

PMID- 20814790
TI  - Interleukin-1 receptor antagonist attenuates cyclophosphamide-induced mucositis
      in a murine model.
AB  - PURPOSE: Cyclophosphamide is a cytotoxic chemotherapy drug that causes severe
      damages to hematopoietic and gastrointestinal systems. The aim of this study is
      to evaluate the protective effects of recombinant human interleukin-1 receptor
      antagonist (rhIL-1Ra) on chemotherapy-induced mucositis (CIM) in a murine model
      of cyclophosphamide chemotherapy. METHODS: In single chemotherapy models, equal
      numbers of gender-matched Balb/c mice were administered intraperitoneal
      injections of rhIL-1Ra at a dose of 1 mg/kg/day or vehicle for 5 continuous days,
      followed by single intraperitoneal injection of cyclophosphamide at doses of 100,
      300, 400 or 550 mg/kg. In multiple cycles of chemotherapy models, mice were
      administered rhIL-1Ra or vehicle for 5 days, followed by cyclophosphamide
      injection at a dose of 300 mg/kg. The course has been repeated for 2 or 3 times
      with a 1-month break in between. In continuous chemotherapy models, mice were
      administered rhIL-1Ra or vehicle for 5 days, followed by cyclophosphamide
      injections at doses of 150 or 200 mg/kg/day for 3 days. Body weight and diarrhea
      were observed in each model. Intestinal morphology was observed in mice received
      300 or 400 mg/kg cyclophosphamide chemotherapy. RESULTS: CIM was induced by
      cyclophosphamide in a dose-dependent manner. RhIL-1Ra attenuated CIM with reduced
      body weight loss, diarrhea, intestinal injuries and mortality after CY
      chemotherapy. CONCLUSIONS: The pretreatment with rhIL-1Ra effectively protected
      murine gastrointestinal system from clinically relevant cyclophosphamide
      regimens. The identification of these protective effects of rhIL-1Ra highlights
      clinical values of this protein for the prevention of CIM.

PMID- 20814791
TI  - Selective degradation of p62 by autophagy.
AB  - The autophagy-lysosome pathway is a highly conserved bulk degradation system in
      eukaryotes. During starvation, cytoplasmic constituents are non-selectively
      degraded by autophagy, and the resulting amino acids are utilized for cell
      survival. By taking advantage of mouse genetics, many physiological functions of
      mammalian autophagy have been uncovered. Growing lines of evidences have revealed
      the essential role of constitutive (or basal) autophagy in cellular homeostasis
      through its selectivity. p62, one of the selective substrates for autophagy,
      plays a key role in the formation of cytoplasmic proteinaceous inclusion, a
      hallmark of conformational diseases such as Alzheimer's disease, Parkinson's
      disease, and various chronic liver disorders. In this review, we discuss the
      physiological roles of the selective turnover of p62 by autophagy and their
      molecular mechanisms.

PMID- 20814792
TI  - Selecting genetic transformants of indica and indica-derived rice cultivars using
      bispyribac sodium and a mutated ALS gene.
AB  - Bispyribac sodium (BS), a pyrimidinyl carboxy herbicide, is a well-known
      inhibitor of acetolactate synthase (ALS) activity. ALS is an enzyme in the
      biosynthetic pathway for branched-chain amino acids. A mutant form of rice ALS
      (OsmALS [W548L/S627I]) that confers resistance to BS can be used as an in vitro
      selection marker gene for plant transformation. Since indica and indica-derived
      cultivars are thought to have lower BS sensitivity than japonica rice, the
      application of BS as a selectable reagent for genetic transformation in indica
      and indica-derived cultivars is more challenging than for japonica cultivars. In
      this study, callus and seedlings of eight different rice cultivars (five indica
      derived cultivars, two indica cultivars and one japonica cultivar) were tested
      for BS sensitivity. Our study indicates for the first time that callus shows a
      higher sensitivity to BS than seedlings in indica and indica-derived cultivars.
      We used BS with OsmALS [W548L/S627I] to select transformed calli, and transgenic
      rice plants from indica and indica-derived cultivars were successfully obtained.

PMID- 20814793
TI  - Meiotic behavior of pollen mother cells in relation to ploidy level of somatic
      hybrids between Solanum tuberosum and S. chacoense.
AB  - Potato somatic hybrids obtained by protoplast fusion between Solanum tuberosum
      (4x) and Solanum chacoense (2x) were investigated for genome stability and
      meiotic behavior associated with the pollen viability in order to elucidate the
      mechanism influencing the fertility of the somatic hybrids. The ploidy level
      detections conducted in 2004 and 2007 demonstrated that 68 out of 108 somatic
      hybrids had their ploidy level changed to be uniform and euploidy after
      successive in vitro subcultures, which mainly occurred in octaploids, aneuploids,
      and mixoploids, while 74% hexaploids were still stable in their genome dosage in
      2007. Different types of abnormal meiotic behavior were observed during the
      development of pollen mother cells (PMCs) including the formation of univalents,
      multivalents, laggard chromosomes, and chromosomal bridges, as well as triads and
      polyads. A higher proportion of abnormal meiosis seemed to be accompanied with a
      genome dosage higher than the hexaploids expected in this study. A significant
      positive correlation between defective PMCs and the number of small pollen grains
      and negative correlation between number of small pollen grains and pollen
      viability strongly suggested that abnormal meiosis could be a causal factor
      influencing the fertility of the somatic hybrids. The hexaploids with stable
      genome dosage and a certain level of fertility will have great potential in a
      potato breeding program.

PMID- 20814794
TI  - Evaluation of an ergonomically modified bed to enhance mobilization in geriatric
      rehabilitation. A pilot study.
AB  - The number of older patients with decreased capacity to independently perform a
      sit-to-stand transfer will increase during the next decade. It was hypothesized
      that an ergonomically modified bed prototype would either allow patients to stand
      up from the prototype independently or with reduced impact on the lower
      extremities. Standing up from the prototype was examined by force plate
      measurements in 30 patients of a geriatric rehabilitation hospital (median age
      83.5 years). Nine of the patients were not able to stand up from the bed without
      arm rests, but were able to stand up with the help of arm rests. In those 21
      patients, able to stand up even without arm rests, the use of arm rests caused a
      lower maximum vertical ground reaction force (p=0.03). No differences in quality
      concerning using or not using the armrests were documented neither for the time
      to stand up nor for symmetry of ground reaction force. In summary, the study
      shows that an ergonomically modified bed adds increased independency during the
      sit-to-stand transfer in selected patients. The reduction of peak vertical ground
      reaction force by using arm rests could be beneficial for certain patient groups.

PMID- 20814795
TI  - Satisfaction and use of personal emergency response systems.
AB  - BACKGROUND: Despite a wide distribution, little is known about the relationship
      between subscriber satisfaction and the extent of use or non-use of personal
      emergency response systems (PERS). OBJECTIVES: To examine the degree of
      satisfaction with PERS, the wearing time and its use in case of a fall. STUDY
      DESIGN AND SETTING: Telephone and face-to-face interviews were conducted with 52
      elderly community-dwelling PERS users. RESULTS: PERS subscribers were very
      satisfied with their device; however, 24% of the participants reported that they
      never wear the alarm button, and only 14% wear it 24 hours each day. After falls
      PERS was not activated by 83% (n=11) of the subscribers who fell alone and lay on
      the floor longer than 5 minutes. None of the five different satisfaction measures
      and only the subscriber's estimation of relevance of the PERS showed to be a
      significant predictor of PERS use in daily life. CONCLUSIONS: High rates of non
      use of PERS in everyday life and after falls can be found. Subscribers'
      estimation of relevance but not satisfaction predicts the usage of PERS in
      everyday life. Further research is needed to better understand the reasons not
      using a PERS.

PMID- 20814796
TI  - [Evaluation of new technologies by residents and staff in an institutional
      setting. Findings of the BETAGT project].
AB  - BACKGROUND: The aim of the substudy that was conducted as part of the project
      "Bewertung neuer Technologien durch Bewohner und Personal im Altenzentrum
      Grafenau der Paul Wilhelm von Keppler-Stiftung und Prufung des Transfers ins
      hausliche Wohnen" (BETAGT) was to have residents and staff members in nursing
      homes with limited technological equipment complete a questionnaire about their
      life-long technological experiences and their general technological attitude.
      Furthermore, specific technological devices and systems were evaluated in terms
      of their potential with respect to safety, privacy, or help in decreasing burden.
      Data were collected using a newly developed brief questionnaire. SAMPLE AND
      METHODS: A total of 84 residents and 109 staff members sampled from 11 different
      institutions were asked about their life-long technology experiences, general
      attitudes towards technology as well as attitudes towards specific technological
      devices. Residents' opinions were assessed via brief structured interviews; a
      structured questionnaire was given to the staff members to complete. The
      technological devices to be evaluated were introduced via pictured descriptions.
      RESULTS: Residents and staff members showed a positive attitude towards
      technology. With regard to the potential of new technologies, residents and staff
      members expect different effects on several dimensions of quality of life. Both
      groups rated the potential of the dimension of safety to be highest. CONCLUSION:
      Contrary to widely held opinion, older adults living in institutions do not, in
      general, seem to be too critical about new technology. From the staff members'
      point of view, modern technology can be integrated into daily care routines of a
      nursing home, but the potentials of new technologies are considered in a very
      differential manner.

PMID- 20814797
TI  - Improvement of balance after audio-biofeedback. A 6-week intervention study in
      patients with progressive supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is a neurodegenerative disease with no
      sufficient treatment options to date. The most devastating symptom is the loss of
      balance with consecutive falls. Based on the observation that postural control
      improved in patients with vestibular dysfunction after audio-biofeedback
      training, we tested the effects of this training in PSP patients. Eight PSP
      patients were included into an uncontrolled 6-week intervention trial. The focus
      of the training was the improvement of posture and dynamic balance by using audio
      biofeedback. The device was well accepted. No adverse events occurred. A
      significant improvement in the Berg Balance Scale was observed (T2 vs. T1,
      p=0.016), which remained significant at the 4-week follow-up (T3 vs. T1,
      p=0.008). Significant improvement of the Parkinson's disease questionnaire was
      demonstrated. No significant changes were found in the Timed Up-and-Go Test, the
      Five Chair Rise Test, and in specific clinical scales. To our knowledge, the
      present study is the first to demonstrate that audio-biofeedback training with
      PSP patients is associated with improvements of balance and psychosocial aspects.

PMID- 20814798
TI  - Use of virtual reality technique for the training of motor control in the
      elderly. Some theoretical considerations.
AB  - Virtual augmented exercise, an emerging technology that can help to promote
      physical activity and combine the strengths of indoor and outdoor exercise, has
      recently been proposed as having the potential to increase exercise behavior in
      older adults. By creating a strong presence in a virtual, interactive
      environment, distraction can be taken to greater levels while maintaining the
      benefits of indoor exercises which may result in a shift from negative to
      positive thoughts about exercise. Recent findings on young participants show that
      virtual reality training enhances mood, thus, increasing enjoyment and energy.
      For older adults virtual, interactive environments can influence postural control
      and fall events by stimulating the sensory cues that are responsible in
      maintaining balance and orientation. However, the potential of virtual reality
      training has yet to be explored for older adults. This manuscript describes the
      potential of dance pad training protocols in the elderly and reports on the
      theoretical rationale of combining physical game-like exercises with sensory and
      cognitive challenges in a virtual environment.

PMID- 20814799
TI  - [Functional capabilities of users of mobility devices after femoral hip fracture.
      A comparison study].
AB  - BACKGROUND: The present study investigates the functional skills and capabilities
      of a sample of 105 patients treated at the Lutheran Geriatric Center Berlin after
      a hip fracture during a period of two years between 2004 and 2006. PATIENTS AND
      METHODS: Geriatric assessment instruments (Barthel index, Instrumental Activities
      of Daily Living Scale (IADL), Timed Up & Go (TUG), Tinetti, grip strength,
      Geriatric Depression Scale (GDS)) were implemented to measure the functional
      capabilities in this prospective study. The subjects were divided into three
      groups, characterized by the type of mobility device they used: crutches, a four
      wheeled walker, or a wheel chair. Furthermore, the data were measured at three
      test intervals (t(0:): baseline before discharge, t(1): 4 weeks after discharge,
      t(2): 4 months after discharge). RESULTS: The results of the study differ
      significantly for each of the three groups at the different test intervals
      (Barthel index, IADL, TUG, Tinetti, grip strength, all p<0.000, ANOVA). The
      results of our investigation demonstrate a substantial difference in increase,
      stagnation or deterioration of capabilities for patients in all three groups.
      However, from t(1) to t(2) only the group using crutches as a mobility device
      demonstrated the highest increase of their capabilities in this specific areas
      (Tinetti, grip strength, IADL, TUG, p<=0.05, general linear model). The results
      of the study differ significantly for each of the three groups at the different
      test intervals (Barthel index, IADL, TUG, Tinetti, grip strength, all p <0.000,
      ANOVA). The results of our investigation demonstrate substantial differences in
      all three groups with respect to increase, stagnation, or deterioration of
      capabilities. However, from t(1) to t(2) only the group using crutches as a
      mobility device demonstrated the highest increase of their capabilities in these
      specific areas (Tinetti, grip strength, IADL, TUG, p<=0.001, general linear
      model) CONCLUSION: A group-specific approach, based on the mobility devices used,
      allowed for better differentiation of functional capabilities after femoral hip
      fracture.

PMID- 20814800
TI  - Alteration of mtDNA copy number, mitochondrial gene expression and extracellular
      DNA content in mice after irradiation at lethal dose.
AB  - High steady-state transcriptional activity is essential for normal mitochondrial
      function. The requisite transcription rate is satisfied in part by high copy
      number of mitochondrial DNA (mtDNA). In the present study, we analyze mtDNA copy
      number by real-time PCR in nucleated blood cells from control mice and mice
      exposed to 1- or 10-Gy X-radiation. Transcription of the oxidative
      phosphorylation-associated genes cytb, atp6, nd4, nd2 and d-loop region was
      monitored in these nucleated blood cells similarly by real-time PCR. We observed
      a 50% decrease in the ratio of mitochondrial to nuclear DNA (mtDNA/nDNA) in blood
      cells, while the mtDNA/nDNA ratio in serum increased. After a lethal 10-Gy dose
      of X-irradiation, we observed an 80% decrease in the number of circulating
      lymphocytes. In response to a 10-Gy radiation dose, we observed transiently
      increased mtDNA/nDNA ratio and transcription within the initial 5 h post
      treatment. At 24-72 h, the mtDNA/nDNA ratio in surviving cells was reduced to the
      level observed in blood cells irradiated with 1 Gy. We observed a decrease in the
      serum mtDNA/nDNA ratio due to an increase in nDNA content rather than a decrease
      in mtDNA. Taken together, results presented herein suggest that the mtDNA/nDNA
      ratio may be of clinical value potentially as a diagnostic tool, particularly in
      oncology patients undergoing radiation therapy.

PMID- 20814801
TI  - Test-retest reliability of the nociceptive withdrawal reflex and electrical pain
      thresholds after single and repeated stimulation in patients with chronic low
      back pain.
AB  - Recent studies have shown that the nociceptive withdrawal reflex threshold (NWR
      T) and the electrical pain threshold (EP-T) are reliable measures in pain-free
      populations. However, it is necessary to investigate the reliability of these
      measures in patients with chronic pain in order to translate these techniques
      from laboratory to clinic. The aims of this study were to determine the test
      retest reliability of the NWR-T and EP-T after single and repeated (temporal
      summation) electrical stimulation in a group of patients with chronic low back
      pain, and to investigate the association between the NWR-T and the EP-T. To this
      end, 25 patients with chronic pain participated in three identical sessions,
      separated by 1 week in average, in which the NWR-T and the EP-T to single and
      repeated stimulation were measured. Test-retest reliability was assessed using
      intra-class correlation coefficient (ICC), coefficient of variation (CV), and
      Bland-Altman analysis. The association between the thresholds was assessed using
      the coefficient of determination (r (2)). The results showed good-to-excellent
      reliability for both NWR-T and EP-T in all cases, with average ICC values ranging
      0.76-0.90 and average CV values ranging 12.0-17.7%. The association between
      thresholds was better after repeated stimulation than after single stimulation,
      with average r (2) values of 0.83 and 0.56, respectively. In conclusion, the NWR
      T and the EP-T are reliable assessment tools for assessing the sensitivity of
      spinal nociceptive pathways in patients with chronic pain.

PMID- 20814805
TI  - Big brains are not enough: performance of three parrot species in the trap-tube
      paradigm.
AB  - The trap-tube task has become a benchmark test for investigating physical
      causality in vertebrates. In this task, subjects have to retrieve food out of a
      horizontal tube using a tool and avoiding a trap hole in the tube. Great apes and
      corvids succeeded in this task. Parrots with relative brain volumes comparable to
      those of corvids and primates also demonstrate high cognitive abilities. We
      therefore tested macaws, a cockatoo, and keas on the trap-tube paradigm. All nine
      parrots failed to solve the task. In a simplified task, trap tubes with a slot
      inserted along the top were offered. The slot allowed the birds to move the
      reward directly with their bills. All but one individual solved this task by
      lifting the food over the trap. However, the parrots failed again when they were
      prevented from lifting the reward, although they anticipated that food will be
      lost when moved into the trap. We do not think that the demanding use of an
      external object is the main reason for the parrots' failure. Moreover, we suppose
      these parrots fail to consider the trap's position in the beginning of a trial
      and were not able to stop their behaviour and move the reward in the trap's
      opposite direction.

PMID- 20814804
TI  - Increased liver elasticity in patients with biliary obstruction.
AB  - BACKGROUND: Transient elastography (with the FibroScan(r) apparatus) is a
      recently developed method for evaluating the severity of liver fibrosis by
      measuring liver elasticity. Liver elasticity may differ from the normal level in
      patients with obstructive jaundice because the retained bile may expand the
      liver. Because little is known about liver elasticity in patients with
      obstructive jaundice, we evaluated this feature in these patients. METHODS:
      Between April 2007 and April 2008, 178 patients with biliary or pancreatic
      disease underwent transient elastography at the University of Tokyo Hospital. We
      excluded 77 patients because of concomitant cirrhotic liver disease, liver
      tumors, or a history of abdominal surgery. The remaining 101 patients were
      included in the study and were divided into obstructive jaundice (OJ; n = 43) and
      nonobstructive jaundice (NJ; n = 58) groups. RESULTS: The basic patient
      characteristics did not differ significantly between the two groups, except for
      the causative diseases. The mean liver elasticity was significantly higher in the
      OJ group than in the NJ group (12.0 vs. 6.2 kPa, p < 0.01). In 24 patients from
      the OJ group, transient elastography was performed before and after biliary
      drainage; there was a marked reduction in the elasticity after the procedure in
      these patients (p < 0.01). CONCLUSIONS: Liver elasticity increases in patients
      with biliary obstruction. This increase is reduced after biliary drainage,
      implying that the increased FibroScan(r) values before drainage are not due to
      liver fibrosis, but to temporarily increased elasticity.

PMID- 20814803
TI  - Sensory input pathways and mechanisms in swallowing: a review.
AB  - Over the past 20 years, research on the physiology of swallowing has confirmed
      that the oropharyngeal swallowing process can be modulated, both volitionally and
      in response to different sensory stimuli. In this review we identify what is
      known regarding the sensory pathways and mechanisms that are now thought to
      influence swallowing motor control and evoke its response. By synthesizing the
      current state of research evidence and knowledge, we identify continuing gaps in
      our knowledge of these mechanisms and pose questions for future research.

PMID- 20814806
TI  - Acute kidney injury in a child with MCNS during cyclosporine A and acyclovir
      treatment.

PMID- 20814807
TI  - Three-year extension study of lanthanum carbonate therapy in Japanese
      hemodialysis patients.
AB  - BACKGROUND: Lanthanum carbonate is a non-aluminum, non-calcium phosphate binder.
      Its efficacy and its safety profile up to 1 year have been reported in Japanese
      hemodialysis patients. METHODS: The present study was an extension of the earlier
      study. One hundred and forty-five patients were enrolled in the original 1 year
      observational Phase III study. After 1 year of treatment, 63 patients continued
      with further lanthanum treatment. Lanthanum carbonate was administered at 750
      4,500 mg/day for up to 156 weeks (3 years). The reduction in serum phosphate was
      used to evaluate efficacy, and laboratory markers of bone turnover were
      monitored. RESULTS: The serum phosphate level was maintained at a significantly
      lower level (P < 0.05) than the baseline level during the 3-year study period.
      Most of the drug-related adverse events were mild and were mainly
      gastrointestinal disorders. The safety profile of lanthanum during 3 years of
      treatment was similar to that seen in the previous study. There were no
      clinically relevant changes in vital signs or the electrocardiogram. Bone
      turnover markers, such as osteocalcin, bone-specific alkaline phosphatase, and
      crosslinked N-telopeptide of type I collagen, showed no clinically relevant
      changes. CONCLUSION: Lanthanum therapy was able to reduce and maintain the serum
      phosphate level within the K/DOQI and JSDT guideline ranges in Japanese dialysis
      patients for 3 years.

PMID- 20814808
TI  - (E)-N-[(3,4-dimethoxyphenethyl)]-N-methyl-3-(3-pyridyl)-2-propenamide (TJN-331)
      inhibits mesangial expansion in experimental IgA nephropathy in ddY mice.
AB  - BACKGROUND: TJN-331 is an inhibitor of transforming growth factor beta1 (TGF
      beta1) production that has similar structural features to the natural product
      acteoside. This study was performed to examine the antinephritic effects of TJN
      331 in a mouse model of experimental IgA nephropathy. MATERIALS AND METHODS: IgA
      nephropathy was induced in ddY mice by oral administration of bovine gamma
      globulin, followed by reticuloendothelial blocking by colloidal carbon injection
      and heminephrectomy. Effects of TJN-331 were examined over oral administration
      periods from 10 to 15 weeks after the third colloidal carbon injection.
      Intravenous administration of a TGF-beta1-neutralizing antibody was used to
      investigate the role of TGF-beta1 in IgA nephropathy. RESULTS: Administration of
      TJN-331 or captopril prevented elevation of serum creatinine. Histopathological
      examination after both experimental periods showed that TJN-331 inhibited
      increases in the mesangial matrix index and the number of nuclei per glomerular
      cross-section, compared with in untreated ddY mice with IgA nephropathy. TJN-331
      prevented increase in glomerular TGF-beta1 staining without affecting IgA. In the
      in vitro study, TJN-331 prevented total TGF-beta1 production from splenocytes
      stimulated with concanavalin A. A neutralizing antibody against TGF-beta1
      prevented increase in the mesangial matrix index and the number of glomerular
      cells per cross-sectional area. CONCLUSION: These results suggest that TJN-331 is
      effective against IgA nephropathy in ddY mice and acts via suppression of TGF
      beta1 production in glomeruli.

PMID- 20814809
TI  - De novo malignant craniopharyngioma: case report and literature review.
AB  - Malignant or anaplastic craniopharyngioma, first described in 1987 by Akachi and
      coworkers, is a rare occurring craniopharyngioma characterized by cytologic
      atypia and poor prognosis. Fifteen cases have been previously reported, two of
      which have been defined de novo, i.e. not developing from a previously treated
      benign craniopharyngioma; both these patients died in the early post-operative
      period. Herein we describe the case of a 66-year-old female who presented with
      visual disturbance and radiological evidence of a sellar and suprasellar tumor.
      The patient underwent trans-sphenoidal biopsy followed by pterional craniotomy
      with partial tumor removal. Histological diagnosis documented a malignant
      adamantinomatous type craniopharyngioma. The patient received adjuvant
      radiotherapy with a significant tumor reduction. She remained in good clinical
      conditions for 10 months; she deteriorated and died, due to tumor progression, 15
      months after diagnosis. Malignant craniopharyngioma is a rare primary malignant
      tumor of the sellar region. This is the first case of de novo malignant
      craniopharyngioma with significant follow-up.

PMID- 20814810
TI  - Acquired thrombotic thrombocytopenic purpura: puzzles, curiosities and
      conundrums.
AB  - We report a case of acquired thrombotic thrombocytopenic purpura (TTP) in a 34
      year old patient with a prior diagnosis of systemic lupus erythematosis (SLE) who
      was recently started on hydroxychloroquine. Presenting symptoms included fevers,
      sore throat and productive cough with progressive weakness, dyspnea on exertion,
      hemoptysis and dark urine. Initial laboratory abnormalities were consistent with
      an acute microangiopathic hemolytic anemia and severe thrombocytopenia. At the
      time of admission, the patient's lupus was highly active as evident by his high
      SLE Disease Activity Index (SLEDAI) score. He was later also found to have
      severely reduced ADAMTS-13 levels and a positive antibody assay. This case
      highlights the occasional difficulty in pinpointing the exact etiology of TTP as
      well as establishes a possible novel drug association between hydroxychloroquine
      and TTP development.

PMID- 20814811
TI  - Effect of pheromone dispenser density on timing and duration of approaches by
      peachtree borer.
AB  - The timing and duration of approaches by male peachtree borer Synanthedon
      exitiosa Say (Lepidoptera: Sesiidae) to commercial pheromone dispensers placed
      singly or at high density in peach orchards was determined by using field
      deployed video cameras and digital video recorders. Cameras were trained on one
      dispenser, and one standard lure was placed in a peach orchard, and on 12
      dispensers in a separate orchard where dispensers for mating disruption had been
      placed at 371 per hectare. Male moth approaches were video recorded at the peak
      of peachtree borer annual flight, from 13 to 18 August 2009. The mean approach
      timing (h:min:sec+/-SD) during the study period was 11:33:12 +/- 00:46:43,
      11:43:52 +/- 00:45:58, and 11:41:21 +/- 00:45:54 AM with the single dispenser,
      high-density dispensers, and lure, respectively. Day-to-day variability in
      approach timings suggested that there were no biologically significant
      differences among treatments. The frequency distribution of approach durations
      varied among treatments, as the high-density dispensers had mostly short
      approaches, while the distribution of approaches to the single dispenser and lure
      was wider. The median (interquartile range) approach duration was 3 (2-4), 1 (1
      2), and 4 (2-6) seconds with the single dispenser, high-density dispensers, and
      lure, respectively. The relative rank of median approach durations was constant
      throughout the period, indicating differences among treatments. This study showed
      that the presence of pheromone dispensers for mating disruption did not cause an
      advancement of peachtree borer diel rhythm of response. Shorter approaches to
      dispensers placed at high density than singly suggest that dispenser
      retentiveness is not constant with peachtree borer, which may bias estimates of
      disruption activity as a function of dispenser density.

PMID- 20814812
TI  - Immunochemical studies on catechol-estrogen modified plasmid: possible role in
      rheumatoid arthritis.
AB  - INTRODUCTION: Increased concentrations of estrogen metabolites
      (catecholestrogens) have been found in rheumatoid arthritis (RA) but the exact
      patho-etiology remains elusive. METHODS: The binding of antibodies from the sera
      of RA patients and control subjects to native and modified DNA was studied by
      direct binding and inhibition ELISA, quantitative precipitin titration.
      Experimentally induced antibodies were also checked to detect oxidative lesions
      in the DNA as well as for the estimation of 8-hydroxy-2'-deoxyguanosine (8-OHdG)
      levels in different fluids of RA. RESULTS: Anti-DNA IgG from RA sera, exhibited
      increased recognition of modified DNA than native DNA (nDNA; P < 0.001). The
      relative affinity of anti-DNA antibodies for modified and nDNA was in the order
      of 1.85 * 10(-7), 1.23 * 10(-7), and 1.2 * 10(-6). Samples of DNA from RA
      patients showed a significant inhibition in the induced antibody activity in
      comparison to DNA isolates from controls (P < 0.001). The concentration of 8-OHdG
      evaluated by induced antibody in RA patients was found to be significantly higher
      than controls ((P < 0.0001, P < 0.01, P < 0.05). CONCLUSION: High binding of
      modified DNA with the IgG from RA patient might explain possible antigenic role
      of 4-OHE(2)-modified DNA in the production of anti-DNA antibodies. In addition,
      the induced antibodies have been shown to represent an alternative immunochemical
      probe to detect oxidative lesions in DNA as well as for the estimation of 8-OHdG
      levels in different body fluid of RA patients, which may be used as marker in the
      diagnosis of the disease.

PMID- 20814813
TI  - Beneficial effect of Eucommia polysaccharides on systemic lupus erythematosus
      like syndrome induced by Campylobacter jejuni in BALB/c mice.
AB  - The stem bark of Eucommia ulmoides Oliv. is commonly used for the treatment of
      hypertension, rheumatoid arthritis, lumbago, and ischialgia in traditional
      Chinese medicine. This study was to determine whether the crude polysaccharides
      (EUPs) isolated from the stem bark of E. ulmoides had beneficial effects on lupus
      like syndrome in mice. BALB/c mice were immunized with CJ-S(131) in Freund's
      complete adjuvant on day 0, and then boosted on day 14. EUPs 15 or 30 mg kg(
      1).day(-1), or prednisone 5 mg kg(-1).day(-1) was given to BALB/c mice
      intragastrically from day 0 to 34. Treatment with EUPs 15 or 30 mg kg(-1).day(-1)
      for 35 days protected kidney from glomerular injury with reduced immunoglobulin
      deposition and lowered proteinuria. The increased production of serum
      autoantibodies and total immunoglobulin G (IgG) was also inhibited. These
      findings suggested that Eucommia polysaccharides had a beneficial effect on
      systemic lupus erythematosus-like syndrome induced by CJ-S(131) in BALB/c mice.

PMID- 20814814
TI  - Effect of facial self-resemblance on the startle response and subjective ratings
      of erotic stimuli in heterosexual men.
AB  - Cues of kinship are predicted to increase prosocial behavior due to the benefits
      of inclusive fitness, but to decrease approach motivation due to the potential
      costs of inbreeding. Previous studies have shown that facial resemblance, a
      putative cue of kinship, increases prosocial behavior. However, the effects of
      facial resemblance on mating preferences are equivocal, with some studies finding
      that facial resemblance decreases sexual attractiveness ratings, while other
      studies show that individuals choose mates partly on the basis of similarity. To
      further investigate this issue, a psychophysiological measure of affective
      processing, the startle response, was used in this study, assuming that
      differences in approach motivation to erotic pictures will modulate startle. Male
      volunteers (n = 30) viewed 30 pictures of erotic female nudes while startle
      eyeblink responses were elicited by acoustic noise probes. The female nude
      pictures were digitally altered so that the face either resembled the male
      participant or another participant, or were not altered. Non-nude neutral
      pictures were also included. Importantly, the digital alteration was undetected
      by the participants. Erotic pictures were rated as being pleasant and clearly
      reduced startle eyeblink magnitude as compared to neutral pictures. Participants
      showed greater startle inhibition to self-resembling than to other-resembling or
      non-manipulated female nude pictures, but subjective pleasure and arousal ratings
      did not differ among the three erotic picture categories. Our data suggest that
      visual facial resemblance of opposite-sex nudes increases approach motivation in
      men, and that this effect was not due to their conscious evaluation of the erotic
      stimuli.

PMID- 20814815
TI  - Phase II, double-blind, randomized trial of capecitabine plus enzastaurin versus
      capecitabine plus placebo in patients with metastatic or recurrent breast cancer
      after prior anthracycline and taxane therapy.
AB  - Capecitabine is frequently used in the treatment of recurrent/progressive
      metastatic breast cancer (MBC) after prior anthracycline and taxane therapy. With
      the intention of improving the efficacy of single agent capecitabine, we
      initiated a randomized, double-blind, placebo-controlled Phase II study of the
      novel serine/threonine kinase inhibitor enzastaurin in combination with
      capecitabine in a heavily pretreated patient population. Patients received
      capecitabine 1,250 mg/m(2) twice daily plus enzastaurin 500 mg/day, or
      capecitabine plus placebo. The capecitabine was administered for the first 14
      days of each 21 day cycle. The primary outcome was progression-free survival
      (PFS) using the log-rank test (1-sided significance level of 0.20). Of 109
      patients assessed for eligibility, 85 were enrolled, randomized, and treated (42
      and 43 patients in each respective treatment group). The study was terminated
      early following a preplanned futility analysis. Median PFS (95% CI) was 2.8 (2.1
      4.6) months with capecitabine plus enzastaurin versus 4.3 (2.9-6.2) months with
      capecitabine plus placebo (adjusted hazard ratio: 1.728 [1.00-2.97]; P = 0.048).
      Median overall survival (95% CI) was lower with capecitabine plus enzastaurin
      than with capecitabine plus placebo (9.9 [7.0-16.6] months vs 14.9 [9.9-19.3]
      months, P = 0.181). Grade 3/4 adverse events were more frequent with capecitabine
      plus enzastaurin (42.9% vs 32.6%). Given the lack of PFS benefit, capecitabine
      plus enzastaurin is unsuitable as therapy for patients with recurrent/progressive
      MBC after prior anthracycline and taxane therapy. This trial is registered on
      www.clinicaltrials.gov (identifier: NCT00437294).

PMID- 20814816
TI  - Clinical significance of high focal adhesion kinase gene copy number and
      overexpression in invasive breast cancer.
AB  - Increased expression and activation of focal adhesion kinase (FAK) was reported
      to be an unfavorable factor in various human cancers, including breast cancer. In
      order to study FAK gene status as a prognostic factor, we evaluated FAK gene copy
      number and FAK protein expression in invasive breast cancer. Tumors from 435
      patients with invasive breast cancer were evaluated for FAK gene status using
      fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) based on
      tissue array method. Survival analyses were performed using the Kaplan-Meier
      method in 267 patients. 42 out of 362 evaluable cases (11.6%) showed high
      polysomy and 22 cases (6.1%) had gene amplification by FISH. 108 out of 393
      evaluable cases (27.5%) showed FAK overexpression by IHC. FAK FISH positivity was
      significantly associated with higher histologic grade, higher T stage, negative
      estrogen receptor expression, negative progesterone receptor expression and
      triple-negative phenotype; FAK overexpression with higher histologic grade and
      triple-negative phenotype. FAK overexpression was noted in 57.8% (37 of 64) of
      FAK FISH+ cases. The concordance of FISH and IHC results for FAK gene was
      observed in 74.9% (271 of 362). Survival analyses revealed the patients with FAK
      FISH+ breast cancer had significantly shorter overall survival and relapse-free
      survival compared to those with FISH- breast cancer. In node-positive breast
      cancer patients who received postoperative systemic treatment, the patients with
      FAK FISH+ showed significantly shorter 5-year survival rates. Despite of high
      significant concordance between the results of FISH and IHC for FAK gene in
      invasive breast cancer, only FAK FISH positivity was an unfavorable prognostic
      factor.

PMID- 20814818
TI  - High-resolution analyses of gene copy number reveal new insights into the
      prognosis and progression of breast cancers.

PMID- 20814817
TI  - Family history of breast cancer in first-degree relatives and triple-negative
      breast cancer risk.
AB  - Triple-negative breast cancer accounts for less than 20% of breast cancers
      overall, but is the predominant subtype among carriers of mutations in BRCA1.
      However, few studies have assessed the association between breast cancer family
      history and risk of triple-negative breast cancer. We examined the relationship
      between having a family history of breast cancer in first-degree relatives and
      risk of triple-negative breast cancer, and risk of two other breast cancer
      subtypes defined by tumor marker expression. We evaluated data collected by the
      Breast Cancer Surveillance Consortium from 2,599,946 mammograms on 1,054,466
      women, among whom 15% reported a first-degree family history of breast cancer.
      Using Cox regression in this cohort, we evaluated subtype-specific associations
      between family history and risk of triple-negative (N = 705), estrogen receptor
      positive (ER+, N = 10,026), and hormone receptor-negative/HER2-expressing (ER-/PR
      /HER2+, N = 308) breast cancer among women aged 40-84 years. First-degree family
      history was similarly and significantly associated with an increased risk of all
      the subtypes [hazard ratio (HR) = 1.73, 95% confidence interval (CI): 1.43-2.09,
      HR = 1.62, 95% CI: 1.54-1.70, and HR = 1.56, 95% CI: 1.15-2.13, for triple
      negative, ER+, and ER-/PR-/HER2+, respectively]. Risk of all the subtypes was
      most pronounced among women with at least two affected first-degree relatives
      (versus women with no affected first-degree relatives, HR(triple-negative) =
      2.66, 95% CI: 1.66-4.27, HR(ER+) = 2.05, 95% CI: 1.79-2.36, HR(ER)-(/PR)-(/HER2+)
      = 2.25, 95% CI: 0.99-5.08). Having a first-degree family history of breast cancer
      was associated with an increased risk of triple-negative breast cancer with a
      magnitude of association similar to that for the predominant ER+ subtype and ER
      /PR-/HER2+ breast cancer.

PMID- 20814819
TI  - The association between biological subtype and locoregional recurrence in newly
      diagnosed breast cancer.
AB  - We investigated the association between the risk of locoregional recurrence (LRR)
      and biological subtypes defined by hormonal receptors (HR) and HER-2 status in
      women with invasive breast cancer (BC). A total of 618 newly diagnosed BC
      patients were identified from a cancer registry within a single institution with
      standardized methods of tumor assessment for estrogen receptor (ER), progesterone
      receptor (PR), and HER-2. Patients were stratified based on surgical treatment,
      breast-conserving therapy (BCT) versus modified radical mastectomy (MRM), as well
      as biological subtypes: HR+/HER-2- (ER-positive or PR-positive, HER-2-negative),
      HR+/HER-2+ (ER-positive or PR-positive, HER-2-positive), HR-/HER-2+ (ER-negative
      and PR-negative, HER-2-positive) and TN (ER-negative, PR-negative and HER-2
      negative). The association between clinicopathological factors, biological
      subtype and LRR was evaluated with univariate and multivariate Cox analysis. With
      a median follow-up of 4.8 years, the rate of LRR was 7.5%. On multivariate
      analysis, TN, tumor size >=2 cm and lymph node (LN) positivity were associated
      with increased risk of LRR (P = 0.023, P = 0.048, and P = 0.0034, respectively).
      In BCT group, HR-/HER-2+ and LN positivity were associated with increased risk of
      LRR (HR 11.13; 95% CI 2.78-44.53; P = 0.0007 and HR 5.40; 95% CI 1.67-17.43; P =
      0.0048, respectively). In MRM group, TN subtype and LN positivity were associated
      with increased risk of LRR (HR 4.72; 95% CI 1.53-14.52; P = 0.0069 and HR 3.23;
      95% CI 1.44-7.29; P = 0.0047, respectively). Compared to HR+/HER-2-, HR-/HER-2+
      treated by BCT and TN treated by MRM showed a significant decrease of 5-year LRR
      free survival (P = 0.0002 and P = 0.002, respectively). Tumor profiling using ER,
      PR, and HER-2 biomarkers is a promising tool to identify patients at high risk of
      LRR based on surgical treatment. Our findings suggest a different follow-up and
      locoregional treatment for patients with HR-/HER-2+ and TN subtypes.

PMID- 20814820
TI  - Distinct function of androgen receptor coactivator ARA70alpha and ARA70beta in
      mammary gland development, and in breast cancer.
AB  - Steroid receptor coactivators are important in regulating the function of the
      receptors in endocrine organ development and in cancers, including breast.
      Androgen receptor (AR) coactivator ARA70, was first identified as a gene fused to
      the ret oncogene and later characterized as an AR coactivator. We previously
      reported that the full length ARA70alpha functions as a tumor suppressor gene and
      that ARA70beta functions as an oncogene in prostate cancer. Here we show that
      both ARA70alpha and ARA70beta function as AR and estrogen receptor (ER)
      coactivators in breast cancer cells. However, ARA70alpha and ARA70beta serve
      different functions in mammary gland development and breast cancer tumorigenesis.
      We observed hypoplastic development of mammary glands in MMTV driven ARA70alpha
      transgenic mice and overgrowth of mammary glands in ARA70beta transgenic mice at
      virgin and pregnant stages. We determined that ARA70alpha inhibited cell
      proliferation, and that ARA70beta promotes proliferation in MCF7 breast cancer
      cells. These effects were observed in hormone-free media, or in media with
      androgen or estrogen, though to varying degrees. Additionally, we observed that
      ARA70beta strongly enhanced the invasive ability of MCF7 breast cancer cells in
      in vitro Matrigel assays. Significantly, decreased ARA70alpha expression is
      associated with increased tendency of breast cancer metastasis. In summary,
      ARA70alpha and ARA70beta have distinct effects in mammary gland development and
      in the progression of breast cancer.

PMID- 20814821
TI  - Novel coumarin-based tyrosinase inhibitors discovered by OECD principles
      validated QSAR approach from an enlarged, balanced database.
AB  - The present work is devoted to the development and application of a multi-agent
      Quantitative Structure-Activity Relationship (QSAR) classification system for
      tyrosinase inhibitor identification, in which the individual QSAR outputs are the
      inputs of a fusion approach based on the voting mechanism. The individual models
      are based on TOMOCOMD-CARDD (TOpological Molecular COMputational Design-Computer
      Aided Rational Drug Design) atom-based bilinear descriptors and Linear
      Discriminant Analysis (LDA) on a novel enlarged, balanced database of 1,429
      compounds within 701 greatly dissimilar molecules presenting anti-tyrosinase
      activity. A total of 21 adequate models are obtained taking into account the
      requirements of the Organization for Economic Cooperation and Development (OECD)
      principles for QSAR validation and present global accuracies (Q) above 84.50 and
      79.27% in the training and test sets, respectively. The resulted fusion system is
      used for the in silico identification of synthesized coumarin derivatives as
      novel tyrosinase inhibitors. The 7-hydroxycoumarin (compound C07) shows potent
      activity for the inhibition of monophenolase activity of mushroom tyrosinase
      giving a value of inhibition percentage close to 100% in vitro assays, by means
      of spectrophotometric analysis. The current report could help to shed some clues
      in the identification of new chemicals that inhibit tyrosinase enzyme, for
      entering in the pipeline of drug discovery development.

PMID- 20814822
TI  - A diversity-oriented synthesis of pyrazolo[4,3-f]quinoline derivatives with
      potential bioactivities via microwave-assisted multi-component reactions.
AB  - Six new series of pyrazolo[4,3-f]quinoline derivatives with potential
      bioactivities were synthesized by the three-component reactions of aromatic
      aldehydes, 5-aminoindazole, and various cyclic 1,3-dicarbonyl compounds under
      microwave irradiation. This protocol has the valuable features of structural
      diversity of products, broader substrate scope, operational simplicity, high
      yields, and short reaction time. Moreover, the structure of compound 88a was
      confirmed by an X-ray crystallographic analysis and attested to the
      chemoselectivity of reaction where 1-methyl barbituric acid participated.

PMID- 20814823
TI  - A comprehensive HADHA c.1528G>C frequency study reveals high prevalence of long
      chain 3-hydroxyacyl-CoA dehydrogenase deficiency in Poland.
AB  - Isolated long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is
      associated with c.1528G>C substitution in the HADHA gene, since most patients
      have the prevalent mutation on at least one allele. As it is known that the
      disease is relatively frequent in Europe, especially around the Baltic Sea, and
      that the majority of Polish LCHADD patients originate from the coastal Pomeranian
      province, partly inhabited by an ancient ethnic group, the Kashubians, we aimed
      to determine the carrier frequency of the prevalent HADHA mutation in various
      districts of Poland with special focus on the Kashubian district. A total of
      6,854 neonatal dried blood samples from the entire country, including 2,976
      Pomeranian neonates of Kashubian origin, were c.1528G>C genotyped. Fifty-nine
      heterozygous carriers for the prevalent c.1528G>C substitution (41 Pomeranian
      children) were detected in the studied group. Our data reveal a geographically
      skewed distribution of the c.1528C allele in the Polish population; in the
      northern Pomeranian province the carrier frequency is 1:73, which is the highest
      frequency ever reported, whereas in the remaining regions it is 1:217. Hence, the
      incidence of LCHADD in Poland is predicted to be 1:118,336 versus 1:16,900 in the
      Pomeranian district. Despite the relative rarity of the disease, screening for
      LCHADD in neonates born in the northern part of Poland, especially those of
      Kashubian origin, is justified. Our data allow us to suggest a probable Kashubian
      origin of the prevalent c.1528G>C mutation. 

PMID- 20814824
TI  - The genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy due to
      mutations in ALDH7A1.
AB  - Pyridoxine-dependent epilepsy is a disorder associated with severe seizures that
      may be caused by deficient activity of alpha-aminoadipic semialdehyde
      dehydrogenase, encoded by the ALDH7A1 gene, with accumulation of alpha
      aminoadipic semialdehyde and piperideine-6-carboxylic acid. The latter reacts
      with pyridoxal-phosphate, explaining the effective treatment with pyridoxine. We
      report the clinical phenotype of three patients, their mutations and those of 12
      additional patients identified in our clinical molecular laboratory. There were
      six missense, one nonsense, and five splice-site mutations, and two small
      deletions. Mutations c.1217_1218delAT, I431F, IVS-1(+2)T > G, IVS-2(+1)G > A, and
      IVS-12(+1)G > A are novel. Some disease alleles were recurring: E399Q (eight
      times), G477R (six times), R82X (two times), and c.1217_1218delAT (two times). A
      systematic review of mutations from the literature indicates that missense
      mutations cluster around exons 14, 15, and 16. Nine mutations represent 61% of
      alleles. Molecular modeling of missense mutations allows classification into
      three groups: those that affect NAD+ binding or catalysis, those that affect the
      substrate binding site, and those that affect multimerization. There are three
      clinical phenotypes: patients with complete seizure control with pyridoxine and
      normal developmental outcome (group 1) including our first patient; patients with
      complete seizure control with pyridoxine but with developmental delay (group 2),
      including our other two patients; and patients with persistent seizures despite
      pyridoxine treatment and with developmental delay (group 3). There is preliminary
      evidence for a genotype-phenotype correlation with patients from group 1 having
      mutations with residual activity. There is evidence from patients with similar
      genotypes for nongenetic factors contributing to the phenotypic spectrum.

PMID- 20814825
TI  - Neurocognitive functioning in school-aged cystinosis patients.
AB  - INTRODUCTION: Cystinosis is an autosomal recessive disorder leading to
      intralysosomal cystine accumulation in various tissues. It causes renal Fanconi
      syndrome and end stage renal failure around the age of 10 years if not treated
      with cysteamine. Children with cystinosis seem to have a normal intelligence but
      frequently show learning difficulties. These problems may be due to specific
      neurocognitive deficits rather than impaired renal function. Whether cysteamine
      treatment can improve cognitive functioning of cystinosis patients is thus far
      unknown. We aim to analyze neurocognitive functioning of school-aged cystinosis
      patients treated with cysteamine in order to identify specific deficits that can
      lead to learning difficulties. PATIENTS AND METHODS: Fourteen Dutch and Belgian
      school-aged cystinosis patients were included. Glomerular filtration rate was
      estimated using the Schwartz formula. Children were tested for general
      intelligence, visual-motor integration, inhibition, interference, sustained
      attention, accuracy, planning, visual memory, processing speed, motor planning,
      fluency and speed, and behavioural and emotional functioning using standardized
      methods. RESULTS: Glomerular filtration rate ranged from 22 to 120 ml min(-1)
      1.73 m(-2). Median full-scale intelligence was below the average of a normal
      population (87, range 60-132), with a discrepancy between verbal (median 95,
      range 60-125) and performance (median 87, range 65-130) intelligence. Over 50% of
      the patients scored poorly on visual-motor integration, sustained attention,
      visual memory, planning, or motor speed. The other tested areas showed no
      differences between patients' and normal values. CONCLUSION: Neurocognitive
      diagnostics are indicated in cystinosis patients. Early recognition of specific
      deficits and supervision from special education services might reduce learning
      difficulties and improve school careers.

PMID- 20814826
TI  - FSH isoform pattern in classic galactosemia.
AB  - Female classic galactosemia patients suffer from primary ovarian insufficiency
      (POI). The cause for this long-term complication is not fully understood. One of
      the proposed mechanisms is that hypoglycosylation of complex molecules, a known
      secondary phenomenon of galactosemia, leads to FSH dysfunction. An earlier study
      showed less acidic isoforms of FSH in serum samples of two classic galactosemia
      patients compared to controls, indicating hypoglycosylation. In this study, FSH
      isoform patterns of five classic galactosemia patients with POI were compared to
      the pattern obtained in two patients with a primary glycosylation disorder
      (phosphomannomutase-2-deficient congenital disorders of glycosylation, PMM2-CDG)
      and POI, and in five postmenopausal women as controls. We used FPLC
      chromatofocussing with measurement of FSH concentration per fraction, and
      discovered that there were no significant differences between galactosemia
      patients, PMM2-CDG patients and postmenopausal controls. Our results do not
      support that FSH dysfunction due to a less acidic isoform pattern because of
      hypoglycosylation is a key mechanism of POI in this disease.

PMID- 20814827
TI  - Overview of homocysteine and folate metabolism. With special references to
      cardiovascular disease and neural tube defects.
AB  - This overview addresses homocysteine and folate metabolism. Its functions and
      complexity are described, leading to explanations why disturbed homocysteine and
      folate metabolism is implicated in many different diseases, including congenital
      birth defects like congenital heart disease, cleft lip and palate, late pregnancy
      complications, different kinds of neurodegenerative and psychiatric diseases,
      osteoporosis and cancer. In addition, the inborn errors leading to
      hyperhomocysteinemia and homocystinuria are described. These extreme human
      hyperhomocysteinemia models provide knowledge about which part of the
      homocysteine and folate pathways are linked to which disease. For example, the
      very high risk for arterial and venous occlusive disease in patients with severe
      hyperhomocysteinemia irrespective of the location of the defect in remethylation
      or transsulphuration indicates that homocysteine itself or one of its "direct"
      derivatives is considered toxic for the cardiovascular system. Finally, common
      diseases associated with elevated homocysteine are discussed with the focus on
      cardiovascular disease and neural tube defects.

PMID- 20814828
TI  - Compromized geranylgeranylation of RhoA and Rac1 in mevalonate kinase deficiency.
AB  - Mevalonate kinase deficiency (MKD) is an autoinflammatory disorder caused by
      mutations in the MVK gene resulting in decreased activity of the enzyme
      mevalonate kinase (MK). Although MK is required for biosynthesis of all
      isoprenoids, in MKD, in particular, the timely synthesis of geranylgeranyl
      pyrophosphate appears to be compromised. Because small guanosine triphosphatases
      (GTPases) depend on geranylgeranylation for their proper signaling function, we
      studied the effect of MK deficiency on geranylgeranylation and activation of the
      two small GTPases, RhoA and Rac1. We demonstrate that both geranylgeranylation
      and activation of the two GTPases are more easily disturbed in MKD cells than in
      control cells when the flux though the isoprenoid biosynthesis pathway is
      suppressed by low concentrations of simvastatin. The limited capacity of
      geranylgeranylation in MKD cells readily leads to markedly increased levels of
      nonisoprenylated and activated GTPases, which will affect proper signaling by
      these GTPases.

PMID- 20814829
TI  - Targeting head and neck squamous cell carcinoma using a novel fusion toxin
      diphtheria toxin/HN-1.
AB  - The current treatment strategies, chemotherapy and radiation therapy being used
      for the management of cancer are deficient in targeted approach leading to
      treatment related toxicities and relapse. Contrarily, fusion toxins exhibit
      remarkable tumor specificity thus emerging as an alternative therapy for the
      treatment of cancer. Diphtheria toxin-HN-1 peptide (DT/HN-1) is a fusion toxin
      designed to target the head and neck squamous cell carcinoma (HNSCC). The aim of
      this study was to construct, characterize, and evaluate the cytotoxicity and
      specificity of DT/HN-1 fusion toxin against the HNSCC cells. The purified DT/HN-1
      fusion toxin was characterized by SDS-PAGE and western blotting. Refolding of
      purified fusion toxins was monitored by fluorescence spectra and circular
      dichroism spectra. The activity of DT/HN-1 fusion toxin was demonstrated on
      various HNSCC cell lines by cell viability assay, cell proliferation assay,
      protein synthesis inhibition assay, apoptosis and cell cycle analysis. The fusion
      toxin DT/HN-1 demonstrated remarkably high degree of cytotoxicity specific to the
      HNSCC cells. The IC(50) of DT/HN-1 fusion toxin was ~1 to 5 nM in all the three
      HNSCC cell lines. The percentage apoptotic cells in DT/HN-1 treated UMB-SCC-745
      cells are 16% compared to 4% in untreated. To further demonstrate the specific
      toxicity of DT/HN-1 fusion toxin towards the HNSCC cells we constructed,
      characterized and evaluated the efficacy of DT protein. The DT protein coding for
      only a fragment of diphtheria toxin without its native receptor binding domain
      failed to exhibit any cytotoxicity on all the cell lines used in this study thus
      establishing the importance of a ligand in achieving targeted toxicity. To
      evaluate the translocation ability of HN-1 peptide, an additional construct
      DTDeltaT/HN-1 was constructed, characterized and evaluated for its cytotoxic
      activity. The fusion toxin DTDeltaT/HN-1 deficient of the translocation domain of
      diphtheria toxin showed no cytotoxicity on all the cell lines clearly indicating
      the inability of HN-1 peptide to translocate catalytic domain of the toxin into
      the cytosol.

PMID- 20814830
TI  - Study of the uncertainty in NO2 chemiluminescence measurements due to the NO-O3
      reaction in sampling lines.
AB  - INTRODUCTION: The change in light intensity that takes place when an ambient air
      sample is drawn into the detection chamber of a chemiluminescence monitor
      generates changes in the concentrations of several species, such as NO(2), NO and
      O(3). Although this phenomenon has been known for several decades, there is still
      no commonly accepted approach on when or how to correct for it in NO(2) and O(3)
      readings. DISCUSSION: In this work, we have assessed the expanded uncertainty of
      two chemiluminescence NO( x ) analysers commercially available according to EN
      14211:2005, with the aim of establishing the maximum allowable standard
      uncertainty due to the reaction between NO and O(3) in the sampling system.
      CONCLUSION: Although this maximum allowable uncertainty cannot be a universal
      value-as it will depend on the performance of each analyser-our results have led
      us to propose the conservative value of 2%. We have also proposed a methodology
      for improving data quality which could be easily implemented by those responsible
      for air quality data validation.

PMID- 20814831
TI  - From medical home to health home.

PMID- 20814832
TI  - Interference microscopy in cell biophysics. 2. Visualization of individual cells
      and energy-transducing organelles.
AB  - The coherent phase microscopy (CPM) provides a convenient and non-invasive tool
      for imaging cells and intracellular organelles. In this article, we consider the
      applications of the CPM method to imaging different cells and energy-transducing
      intracellular organelles (mitochondria and chloroplasts). Experimental data
      presented below demonstrate that the optical path length difference of the
      object, which is the basic optical parameter measured by the CPM method, can
      serve as an indicator of metabolic states of different biological objects at
      cellular and subcellular levels of structural organization.

PMID- 20814833
TI  - Vertical transmission of HIV-an update.
AB  - One of the greatest successes in AIDS research to date has by far been the
      discovery of successful interventions that interrupt the transmission of HIV from
      mother to child. It is however important to note that these successes have
      occurred largely in countries with great resources and the least burden of
      perinatal transmission of HIV. In the developing world wherein currently 95% of
      vertical transmission of HIV occurs, it is highly condemnable that still every
      minute an infected infant is said to be born in spite of the fact that vertical
      transmission is largely preventable, mainly because translating knowledge into
      practice is not always possible or feasible; This has led to a continuous growing
      numbers of children with HIV, thereby making pediatric HIV a looming problem
      rapidly draining the already burdened health care system of these countries. It
      is the need of the hour to appropriately address the challenges to achieve zero
      percent transmission of HIV from an infected mother to her child thereby giving a
      hope for an AIDS-free new generation worldwide.

PMID- 20814834
TI  - Differential diagnosis of hereditary nephrogenic diabetes insipidus with
      desmopressin infusion test.
AB  - PURPOSE: The causes of hereditary nephrogenic diabetes insipidus (HNDI) are the
      mutations in the arginine vasopressin V2 receptor gene (AVPR2) (90%) and
      aquaporin 2 gene (AQP2) (10%). Although it is possible to perform mutation
      analysis where available, differentional diagnosis at clinical bases remains
      valuable. METHODS: In this report we present two cases of HNDI diagnosed at
      clinical bases with a desmopressin infusion test as AQP2 gene mutations. The
      results were verified by genetic analysis to stress that a desmopressin infusion
      test is valuable for differential diagnosis of HNDI. RESULTS: With a desmopressin
      infusion test, factor VIII levels were increased up to 219% and 214%
      respectively, establishing the presence of V2 receptor. With direct sequencing of
      the AQP2 gene, a previously described splicing mutation in a new codon (380) and
      a new frameshift mutation were determined in case 1 and case 2 respectively.
      CONCLUSION: It is concluded that the desmopressin infusion test is a simple and
      reliable method for the diagnosis and differential diagnosis of HNDI in early
      childhood.

PMID- 20814835
TI  - Predictors of intubation in children.
AB  - OBJECTIVE: To estimate the relation of mentohyoid, thyromental and sternomental
      distances to height, weight and age of children with normal airway. METHODS: We
      carried out a prospective, double blind pilot study in 400 children posted for
      elective surgery to measure mentohyoid, thyromental and sternomental distances
      pre-operatively followed by intra-op evaluation of intubation using Cormack and
      Lehane grading. RESULTS: On assessing the contribution of age, height and weight
      to predict mentohyoid, thyromental and sternomental distances in children, the
      best predictor was found to be height (p=0.001)followed by age (p=0.04)of the
      patient. CONCLUSION: We have derived simple formulae to predict mentohyoid,
      thyromental and sternomental distances relevant to airway based on height and age
      of children.

PMID- 20814836
TI  - Community acquired methicillin resistant Staphylococcus aureus: a rare
      presentation.
AB  - INTRODUCTION: Incidence of community acquired methicillin resistant
      staphylococcus aureus (CA-MRSA) is increasing. Toxic shock syndrome (TSS),
      Necrotizing fasciitis (NF), Symmetrical peripheral gangrene (SPG) as a
      manifestation of CA-MRSA are rare in pediatrics. CASE PRESENTATION: We report a
      young boy who presented with TSS, NF and SPG by CA-MRSA following trauma.
      CONCLUSION: CA-MRSA should be taken into consideration as an etiology for these
      type of clinical presentations. Early and aggressive surgical and medical
      intervention are the cornerstone for successful management.

PMID- 20814837
TI  - The prevalence and effects of Pectus Excavatum and Pectus Carinatum on the
      respiratory function in children between 7-14 years old.
AB  - The study involved 1342 primary school students aged 7-14 years who applied to
      Ankara, a primary care center for general health check-up between 2006 and 2007.
      Forty-three students, 35 of whom had PE and 8 of whom had PC, were subjected to
      thorax measurement. All 43 students underwent pulmonary function tests (PFT).The
      prevalence rate of PC was 0.6%, and of PE, 2.6%. The thorax widths of the groups
      were similar (P = 0.273). The thorax circumference and depth of PE group were
      lower than those of the controls (P < 0.05). The probability rate of abnormality
      in PFT scores of PE group was statistically significantly higher than that of the
      controls (P = 0.022) whereas absence of normal PFT scores the difference between
      PC group and the controls was not statistically significant (p = 0.095). The
      results indicate that more than half of the individuals with pectus deformity do
      not have any physical complaints and do not have statistically significant
      differences in their PFT parameters.

PMID- 20814838
TI  - Neonates investigated for influenza-like illness during the outbreak of pandemic
      H1N1 2009: trivial infections but major triage implications.
AB  - We report eight cases of neonates (from birth to 25 days) admitted to the
      neonatal service of a teaching hospital with influenza-like illness during the
      outbreak of pandemic H1N1 2009, and discuss their management and infection
      control issues. Empirical antibiotics were often promptly initiated and timely
      stopped when sepsis was ruled out. Also, there was no pandemic H1N1-09 but
      influenza A (H3N2, n = 1), parainfluenza (type 3, n = 3) and respiratory
      syncytial virus (n = 1) have been isolated. The infants recovered spontaneously
      without any antiviral therapy. There was no outbreak of the respiratory
      infections in the neonatal service during the admissions. Respiratory viral
      infections can occur in neonates although the clinical course may be milder and
      nonspecific. Emergency room and frontline staff must be vigilant of the non
      specific clinical features of infections with respiratory viruses in the neonates
      so that prompt triage and isolation can be implemented to avoid outbreaks in the
      neonatal service.

PMID- 20814839
TI  - Neurodevelopmental and behavioral outcome of very low birth weight babies at
      corrected age of 2 years.
AB  - OBJECTIVE: Neurodevelopmental and behavioral assessment of very low birth weight
      babies (VLBW) at corrected age (CA) of 2 years. METHODS: 127, 110, 99 and 101
      babies <=34 weeks and <=1500 g were followed at CA of 3, 6, 9, 12 months
      respectively for developmental and neurological assessment. DASII (Developmental
      assessment scale for Indian infants) was used at CA of 18 months and preschool
      behavioural checklist (PBCL) at CA 2 years. RESULTS: Of 101 VLBW babies available
      for follow up at CA 1 year, 3 (3%) babies had Cerebral Palsy (CP) and 3% (n = 3)
      had suspect abnormality (mild hypotonia), 11% (n = 11) had gross motor and 8% (n
      = 8) had language abnormality. Their mean mental (MeDQ) and motor (MoDQ)
      quotients were 80.4 +/- 10.7 and 77.2 +/- 13.3 and a score of < 70 was found in
      17% (MeDQ) and 25.7% (MoDQ) VLBW babies. High PBCL score (mean 16.8 +/- 5.4) was
      seen in 84%VLBW babies. On subgroup analysis, 2 babies (5%) in subgroup1 ( n =
      54, <=1200 g,) and 1 (1.6%) in subgroup 2 (n = 78, 1201-1500 g) had CP. Twelve
      (29%) in subgroup 1 had significant language delay (p = 0.004) as compared to 4
      (15%) in subgroup 2 at 1 year. BSID and PBCL scores were comparable. Amongst ELBW
      babies (<1000 g), 6.6% (n = 1) had CP, 25% (n = 3) and 42% (n = 5) had low MeDQ
      and MoDQ respectively and all of them had high PBCL score. AGA and SGA had
      similar outcome. CONCLUSION: VLBW babies need close and longer follow up due to
      high risk of neurodevelopmental and behavioral abnormality.

PMID- 20814840
TI  - Superior mediastinal syndrome due to intrathoracic tuberculosis.
AB  - A 5-year-old boy presented with fever, cough, breathlessness and facial swelling.
      He was pale with distended veins over neck and chest, cervical and axillary
      lymphadenopathy and bilateral expiratory wheeze. Chest radiographs showed
      superior mediastinal widening. A computed tomography scan of the chest revealed
      mediastinal lymph nodes compressing superior vena cava and trachea. Bronchoscopy
      revealed nodular lesions in trachea and bronchi and compression of trachea.
      Broncho-alveolar lavage revealed acid fast bacilli. Diagnosis of superior
      mediastinal syndrome (SMS) secondary to tuberculosis was made and child was
      treated with antitubercular treatment along with oral prednisolone with good
      response.

PMID- 20814841
TI  - The place of pediatric rheumatology in India.
AB  - Rheumatology is a relatively new specialty in the field of Pediatrics in India
      where there are only a few centres of excellence. Awareness about these
      conditions in childhood is lacking and patients are often referred late resulting
      in poor long term outcomes. This article highlights the needs of the paediatric
      rheumatology patients which are complex and should encompass both acute and
      chronic care and also plan a smooth transition to the adult rheumatology world.
      In the year 2010, attaining remission is the goal for every child with a
      rheumatologic disorder, which is seldom achieved for the Indian pediatric
      rheumatologic patient. The article discusses the reasons for poor awareness, the
      current outcome for these patients and details the burden of disease in India.
      The health care delivery system and finally the way forward have been discussed.

PMID- 20814842
TI  - Iron deficiency: beyond anemia.
AB  - Iron deficiency is the most common nutritional disorder affecting at least one
      third of world's population. Though anemia is common manifestation of iron
      deficiency, other effects of iron deficiency on various tissues, organs and
      systems are usually under recognized. Impaired brain development and cognitive,
      behavioural and psychomotor impairment are most worrisome manifestations of iron
      deficiency. Studies have demonstrated that some of these changes occurring during
      period of brain growth spurt (<2 years age) may be irreversible. Association of
      iron deficiency with febrile seizures, pica, breath holding spells, restless leg
      syndrome and thrombosis is increasingly being recognized. Impaired cell-mediated
      immunity and bactericidal function are generally noted in iron-deficient persons;
      however, the findings are inconsistent. Despite proven reversible functional
      immunological defects in vitro studies, a clinically important relationship
      between states of iron deficiency and susceptibility to infections remains
      controversial. Studies from malaria endemic regions have reported increased
      incidence of malaria in association with iron supplementation. These and some
      other aspects of iron deficiency are reviewed in this article.

PMID- 20814843
TI  - Evaluation of a mass measles vaccination campaign among school children aged 7-14
      years old in Denizli, Turkey.
AB  - OBJECTIVE: To determine the pre-campaign level of measles seropositivity and to
      evaluate the effect of a mass measles vaccination campaign on measles
      seroposivity among primary school children in Denizli, Turkey. METHODS: The study
      was completed in two socioeconomically different areas of Denizli, Turkey, with a
      sample size of 520 students. One primary school from each area and one classroom
      from each grade were randomly included in the sample. Before and 2-months after
      the measles mass vaccinations, blood samples were collected from the students and
      measles specific IgGs were studied. RESULTS: The pre-campaign overall
      seropositivity was 74.7%. Post-campaign overall seropositivity increased to
      96.5%. Pre-campaign seropositivity among 8-graders was significantly lower than
      that in other grades (57.5%, p<0.001) and the difference was explained by the
      number of vaccinations 8-graders received. Except for the number of vaccination
      doses, other factors did not have any effect on seropositivity. CONCLUSIONS: The
      mass measles vaccination programs have a potential to control measles for
      developing countries. In addition, more than one dose of measles vaccination is
      required for developing countries.

PMID- 20814844
TI  - Effects of prefeeding oral stimulation on feeding performance of preterm infants.
AB  - OBJECTIVE: To investigate the effects of a prefeeding oral stimulation program on
      the feeding performance of preterm infants. METHODS: A crossover design was used.
      Nineteen preterm infants who were in the transitional time to full oral feeding
      served as their own controls. A 5-min oral stimulation program was applied to
      infants prior to feeding in two of 4 feedings on two consecutive days. Feeding,
      behavioral state, and physiological parameters of infants in the intervention and
      control feeding conditions were compared using SPSS software. RESULTS: There were
      two significant findings: (1) Compared to the control condition, infants in the
      intervention condition achieved a greater intake rate in the initial 5 min of the
      feeding (P = 0.021). (2) After receiving oral stimulation, a higher percentage of
      infants moved to the drowsy or quiet alert state from sleep or restlessness
      before feeding, both on Day 1 (P= 0.016) as well as Day 2 (P = 0.016). No
      significant differences were found in other feeding parameters, feeding-induced
      physiological changes (peripheral oxygen saturation levels and pulse rate) and
      behavioral states between two feeding conditions. CONCLUSIONS: Oral stimulation
      had a modulating effect on the prefeeding behavioral states and short-lived
      beneficial effects on the feeding efficiency of preterm infants.

PMID- 20814846
TI  - Overactive bladder and mixed incontinence.
AB  - Mixed urinary incontinence (MUI) is a complex problem and a difficult one to
      treat. Successful outcome associated with treatment depends on alleviation of not
      one, but two symptoms. This review addresses the definition, etiology, workup,
      and treatment of MUI. It encompasses conservative, pharmacological, and surgical
      therapies along with their outcomes in these complicated patients.

PMID- 20814845
TI  - Cognitive reserve and brain volumes in pediatric acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is associated with long-term, progressive
      cognitive deficits and white matter injury. We measured global and regional white
      and gray matter as well as cognitive function and examined relationships between
      these variables and cognitive reserve, as indicated by maternal education level,
      in 28 young survivors of ALL and 31 healthy controls. Results indicated
      significantly reduced white matter volumes and cognitive testing scores in the
      ALL group compared to controls. Maternal education was inversely related to both
      global and regional white matter and directly related to gray matter in ALL and
      was directly related to both gray and white matter in controls, consistent with
      the cognitive reserve hypothesis. Cognitive performance was associated with
      different brain regions in ALL compared to controls. Maternal education was
      significantly positively correlated with working and verbal memory in ALL as well
      as processing speed and verbal memory in controls, improving models of cognitive
      outcome over medical and/or demographic predictors. Our findings suggest that
      cognitive reserve may be an important factor in brain injury and cognitive
      outcome in ALL. Additionally, children with ALL may experience some neural
      reorganization related to cognitive outcome.

PMID- 20814848
TI  - Different effects of aliskiren and losartan on fibrinolysis and insulin
      sensitivity in hypertensive patients with metabolic syndrome.
AB  - The aim of this study was to compare the effect of aliskiren and losartan on
      fibrinolysis and insulin sensitivity (IS) in hypertensive patients with metabolic
      syndrome. After 2-week placebo period, 76 outpatients with mild to moderate
      hypertension and metabolic syndrome were randomized to aliskiren 300 mg od or
      losartan 100 mg od for 12 weeks. Clinic blood pressure (BP), plasma PAI-1
      antigen, and tPA activity were evaluated after 2, 4, 8, and 12 weeks of
      treatment. At the end of each treatment period patients performed an euglycemic
      hyperinsulinemic clamp and IS was assessed by glucose infusion rate (GIR). Both
      aliskiren and losartan induced a significant and similar SBP/DBP reduction (
      15.6/10.7 mmHg and -15.5/10.5 mmHg, p<0.001 vs. baseline, respectively). Both
      drugs decreased PAI-1 antigen and activity after 2 weeks of treatment;
      subsequently, only the decreasing effect of aliskiren was sustained throughout
      the 12 weeks [-7.5 ng/ml (-31%) p<0.05 vs. baseline], while with losartan PAI-1
      increased at week 12 [+3.6 ng/ml (+15%), p<0.05 vs. baseline and p<0.01 vs.
      aliskiren)]. The tPA activity showed no significant change with aliskiren and a
      decrease with losartan [-0.04 IU/ml (-8%), p<0.05 vs. baseline and p<0.01 vs.
      aliskiren]. Aliskiren significantly increased GIR [+1.4 mg/min/kg (+28%), p<0.01
      vs. baseline] while losartan did not change it [+0.2 mg/min/kg (+4%), NS vs.
      baseline, p<0.05 vs. aliskiren)]. These results indicated that in this type of
      patients, despite similar BP reduction, aliskiren improved the fibrinolytic
      balance as well as IS, while losartan worsened the fibrinolytic balance and did
      not affect IS. The clinical relevance of these different effects remains to be
      clarified.

PMID- 20814849
TI  - Tick-borne meningoencephalitis in a 4.5-month-old infant.
AB  - BACKGROUND: The course of tick-borne encephalitis (TBE) in children is supposed
      to be mild though severe neurological sequelae have been reported. Only
      occasionally infants are affected. PATIENTS AND METHODS: Case report, review of
      literature. RESULTS: We describe the first case of tick-borne encephalitis in a
      4.5-month-old male infant in Germany. 11 days after a tick-bite he developed
      acute illness with fever, focal and generalized seizures. Meningoencephalitis
      caused by the TBE virus was diagnosed by cerebrospinal fluid (CSF) pleocytosis
      and detection of TBE-RNA in the CSF. Neurological follow-up showed no
      abnormalities. CONCLUSIONS: The acute meningoencephalitis in the present case and
      the neurological short and long term morbidity of 3 additional published cases of
      TBE suggest the considerable burden of this disease in infancy. As parents can
      transmit the tick to their infant informations about exposure-prophylactic
      measurements are recommended.

PMID- 20814850
TI  - Re-introduction of kava (Piper methysticum) to the EU: is there a way forward?
AB  - Kava (Piper methysticum) is an effective anxiolytic that has been withdrawn from
      various consumer markets in European countries due to concerns over its
      hepatotoxicity. It is plausible that the reported hepatotoxicity may be due in
      part to plant substitution, or an incorrect cultivar, or plant parts being used
      (such as leaves or bark); thus both the plant chemotype and the plant part used
      may be critical factors. If re-institution of kava in the EU is to occur, more
      evidence is required to determine its safety and efficacy. Furthermore, according
      to current evidence, the study of traditional water soluble rhizome extracts
      using a noble cultivar of kava may be advised. The Kava Anxiety-Lowering
      Medication (KALM) project is due to start in late 2010 to address these
      considerations. The KALM project uses an aqueous rhizome extract of a noble
      cultivar of kava in participants with generalised anxiety and Generalised Anxiety
      Disorder (GAD). The project comprises of 1) an acute RCT, kava (180 mg of
      kavalactones) versus oxazepam and placebo in 20 anxious people, testing effects
      on cognition, mood, anxiety, and driving; 2) an 8-week RCT comparing kava (120 mg
      kavalactones) versus placebo in 100 patients with GAD. To assess differences
      between dosages, non-responders at 3 weeks will be titrated to 240 mg of
      kavalactones. The project will also assess the effects of kava on liver function
      tests and its side effects profile. A novel component of the project is the
      pharmacogenomic exploration of phenotypical responses (GABA system and cytochrome
      P450 markers). The results of the study may be of benefit to sufferers of anxiety
      and the future economy of the Pacific islands, potentially providing an important
      step in the way forward with kava.

PMID- 20814851
TI  - Plasma and brain levels of terpene trilactones in rats after an oral single dose
      of standardized Ginkgo biloba extract EGb 761(r).
AB  - Several studies indicate that the terpene trilactones (TTL) of EGb 761(r) are
      responsible for most of its pharmacological action in the brain . Therefore, we
      investigated the ability of the TTL to cross the blood brain barrier in rats
      after a single oral administration (600 mg/kg) of EGb 761(r) and compared it with
      the plasma levels. In addition, we checked the pharmacokinetic characteristics of
      an application of EGb 761(r) against a similar amount of pure substances. For
      this purpose, we developed a sensitive HPLC-(APCI)-MS method for the
      determination of the Ginkgo biloba TTL (ginkgolide A [GA], B [GB], C [GC] and
      bilobalide [Bb]) in plasma as well as in brain tissue. The following animal study
      shows that the oral application of 600 mg/kg EGb 761(r) results in significant
      GA, GB, and Bb concentrations in plasma as well as in the CNS of the rodents,
      while the GC concentration was below the detection limit of the analytical method
      in both matrices. GA, GB, and Bb brain concentrations showed a rapid increase up
      to 55 ng/g, 40 ng/g, and 98 ng/g with no difference of the characteristic after
      extract or pure substance application. Regarding the plasma levels, significant
      higher C(max) and AUC values were detected after application of the extract EGb
      761(r). These results allow for the first time a discussion of pharmacological
      effects with the knowledge of the pharmacokinetic behavior of the TTL in target
      tissues.

PMID- 20814852
TI  - Hypopigmenting activity of bisabolangelone isolated from Angelica koreana Maxim.
      in alpha-melanocyte stimulating hormone-activated B16 or melan-a cells.
AB  - Tyrosinase is a key enzyme in the biosynthetic pathway of melanin pigments.
      Abnormal accumulation of melanin pigments causes melasma, freckles, and senile
      lentigo, which can be substantially ameliorated by treatment with arbutin or
      other tyrosinase inhibitors. In this study, roots of Angelica koreana Maxim.
      (Umbelliferae) inhibited melanin production in alpha-melanocyte stimulating
      hormone ( alpha-MSH)-activated B16 melanoma cells or melan-a melanocytes. To
      elucidate the hypopigmenting principle of A. koreana, the plant extracts were
      subjected to bioassay-guided phytochemical analysis, resulting in the
      identification of bisabolangelone. Bisabolangelone dose-dependently inhibited
      alpha-MSH-induced melanin production in B16 or melan-a cells with IC(15) values
      of 9-17 uM. The positive control arbutin also inhibited melanin production in B16
      cells with an IC(50) value of 317 uM. Bisabolangelone suppressed alpha-MSH
      inducible protein levels of tyrosinase in B16 cells but could not significantly
      inhibit the catalytic activity of cell-free tyrosinase. Taken together, this
      study indicates that bisabolangelone is the primary hypopigmenting principle of
      A. koreana and may have pharmacological potential in the melanin-associated
      hyperpigmentation disorders.

PMID- 20814853
TI  - Suppression of intracellular calcium levels and inhibition of degranulation in
      RBL-2H3 mast cells by the sesquiterpene lactone parthenolide.
AB  - Pretreatment with parthenolide for 60 min inhibited the antigen-induced
      degranulation of RBL-2H3 mast cells; the IC(50) value being 4.5 +/- 0.4 uM. The
      inhibition was not due to suppression of the phosphatidylinositol 3-kinase
      pathway because the antigen-induced phosphorylation of Akt was not inhibited by
      parthenolide. The antigen-induced increase in intracellular calcium levels was
      prevented by parthenolide, suggesting that parthenolide inhibited the antigen
      induced degranulation by suppressing an increase in intracellular calcium levels.
      In support of this, parthenolide was found to prevent ionomycin-induced
      degranulation by inhibiting an increase in intracellular calcium levels.
      Therefore, parthenolide inhibits the degranulation of mast cells by preventing an
      increase in intracellular calcium levels.

PMID- 20814854
TI  - Chaetoglocins A-D, four new metabolites from the endophytic fungus Chaetomium
      globosum.
AB  - Chaetoglocins A-D (1- 4), four new secondary metabolites, were isolated from the
      solid-fermentation culture of Chaetomium globosum (strain no. IFB-E036), an
      endophytic fungus residing inside the root of Cynodon dactylon. The structures of
      these compounds were elucidated on the basis of detailed spectroscopic evidence
      and by comparing spectroscopic data with those in the literature. Compounds 1 and
      2 displayed antimicrobial activity against the gram-positive bacteria with
      minimum inhibitory concentrations (MIC) between 8 and 32 ug/mL.

PMID- 20814855
TI  - [Evidence-based medicine--principles and impact on plastic surgery].
AB  - The increasing importance of evidence-based medicine (EBM) is the result of an
      increasing demand for a rational decision-making process in healthcare. It has
      been demonstrated that 15-40% of decisions made in healthcare do not have a solid
      scientific basis. This is particularly problematic in times of limited financial
      resources, when reimbursement increasingly depends on how "evidence-based" a
      particular treatment is. Application of EBM principles in plastic surgery is
      therefore no longer an option. This, however, requires a basic understanding of
      the existing levels of evidence. In the present article, principles of EBM will
      be presented. The importance of randomized controlled trials and systematic
      reviews for plastic surgery will be highlighted along with a discussion of the
      quality of the plastic surgical literature based on results of recent systematic
      analyses. The plastic surgical community has appreciated the need for higher
      quality clinical studies. Improvement of the quality of reporting is, however,
      critical.

PMID- 20814856
TI  - [Mechanical ventilation in toxic epidermal necrolysis].
AB  - INTRODUCTION: Toxic epidermal necrolysis (TEN) is associated with a high
      mortality. The need for mechanical ventilation is associated with an increased
      mortality in TEN patients. This study investigates the impact of the timing of
      initiation of the mechanical ventilation on the survival of TEN patients.
      PATIENTS, MATERIALS AND METHODS: A retrospective study of 26 TEN patients was
      carried out. Primary (on admission (group A) and secondary ventilation (>1 day
      after admission (group B) were analysed for an association with mortality.
      RESULTS: 8 patients did not require mechanical ventilation. 18 patients needed
      mechanical ventilation. In group A 8 patients with an epidermolytic body surface
      area (BSA) of 73 +/- 16% and a mean SCORTEN of 3.2 +/- 1.1 were analysed. In
      group B 10 patients with an epidermolytic BSA of 76 +/- 19% and a mean SCORTEN of
      3.8 +/- 0.9 were evaluated. Statistical analysis showed an increased mortality in
      all mechanically ventilated compared with non-ventilated TEN patients (Odds
      ratio: 2.0; 95% CI: 1.26-3.17 p = 0.013). CONCLUSIONS: Mechanical ventilation in
      TEN patients is associated with an increased mortality rate, but the timing of
      initiation of mechanical ventilation does not affect the patient survival rates.

PMID- 20814857
TI  - [Implementation of the interferon-gamma release assay for contact tracing: a 2
      year project in lower Saxony, Germany].

PMID- 20814858
TI  - [Vaccination as a supporting measure to control animal disease outbreaks in
      Europe: Findings for Switzerland].
AB  - Switzerland and the European Union have a non-vaccination policy for many animal
      diseases relevant for trade. Because of the relatively low animal density,
      disease control measures in Switzerland focus on the immediate culling of
      infected animals. However, the use of vaccines as a supporting measure can
      represent an effective option to promptly contain an epidemic and to reduce the
      number of animals to be killed. A prerequisite for the success of vaccination is
      its early, rapid and purposeful implementation. Vaccinations can be cost
      intensive and can entail restrictions in international trade. For the choice of
      the appropriate control measure it is therefore important to thoroughly assess
      the epidemiology, the economic consequences of the control measures and the
      acceptance of these measures by the environment. Because of their special
      epidemiology, vaccination has clear advantages as a preventive measure for vector
      borne diseases.

PMID- 20814859
TI  - [Benefit of clinical and laboratory parameters for the diagnosis of endometritis
      in dairy cows].
AB  - The goal of this work was to answer the question of whether or not there are
      significant differences between cows with abnormal vaginal discharge and cows
      with the diagnosis of puerperal or chronic endometritis, using blood and urine
      parameters. In addition, cows with and without vaginal discharge were examined
      for significant bacteriological differences in uterine mucous samples. The
      question of false positive and false negatives from the diagnosis of endometritis
      was also investigated. A total of 35 matched-pairs (+/-vaginal discharge) from 27
      stables was examined 21 to 63 days post partum. The examination consisted of a
      rectal and vaginal exam, urine and blood samples as well as vaginal swab from the
      corpus uteri using a Folmer-Nielsen-Catheter. Based on the history vaginal
      discharge occurred more frequently in dystocia and retentio secundinarium. Cows
      with a history of distocia and retentio secundinarium showed significantly more
      vaginal discharge. Gammaglutamyltransferase (GGT; p=0.01) and cholesterine
      (p=0.04) were different in cows with endometritis. The bacteriology results
      showed a statistically significant difference (p<0.01) only for Escherichia coli
      and Arcanobacterium pyogenes. The Folmer-Nielsen smears/endometritis showed a
      significant difference between the two groups (p<0.01). In a multivariate
      analysis with final step-back procedure regarding endometritis
      Gammaglutamyltransferase (GGT) and Betahydroxybutteracid (BHB) were significant
      different (p=0.02). The hypothesis vaginal discharge alike endometritis showed
      that 34 % of the clinical suspicious cases were recorded as false negatives. In
      the non-suspicious cases 20 % were diagnosed as false negative.

PMID- 20814860
TI  - [Diagnostic workup of chronic inflammatory bowel disease in the horse].
AB  - The present retrospective study describes the diagnostic workup and collected
      findings in 7 horses with chronic inflammatory bowel disease over the years 2000
      2006. The diagnosis could be confirmed histologically with biopsies taken during
      laparoscopy or laparotomy or during post mortem examination. Weight loss and
      chronic diarrhoea were the most commonly reported clinical findings. Among
      ancillary examinations (fecal analysis, gastroscopy, abdominal ultrasonography,
      rectal mucosal biopsy) the D-xylose absorption test provided the most useful
      information. Although clinical signs and laboratory findings are helpful
      diagnostic tools, a definitive diagnosis is only possible by histological
      analysis of the intestinal segment.

PMID- 20814861
TI  - Prevalence of Campylobacter jejuni, Campylobacter coli and enteric Helicobacter
      in domestic and free living birds in North-Western Italy.
AB  - In order to investigate the prevalence of some thermophilic Campylobacter (C.
      jejuni and C. coli) and enteric Helicobacter (H. pullorum and H. canadensis) in
      domestic and wild birds, a total of 278 bird caecal samples were analyzed over a
      2 year period in North-Western Italy. Samples were collected from poultry raised
      in intensive farming at the slaughterhouse (n=102, group A) and in small scale
      rural farms (n=60, group B) as well as from wild birds (n=116, group C). PCR
      amplifications were carried out on DNA extracted from caecal samples. Molecular
      assays targeted the hipO gene for C. jejuni, the asp gene for C. coli and the 16S
      rRNA gene of H. pullorum/H. canadensis. To differentiate H. pullorum from H.
      canadensis, PCR products were subjected to an ApaLI digestion assay. Prevalence
      of thermophilic Campylobacter and enteric Helicobacter was significantly
      different among groups (p<0.0001). Campylobacter infections were detected in all
      three bird groups (78.4% group A, 18.3% group B and 38.8% group C, respectively),
      Helicobacter infections were only detected in poultry, with H. pullorum infecting
      68.6% of group A and 21.7% of group B birds. H. canadensis was detected in Guinea
      fowls (group A) and for the first time in pheasants (group B). Mixed infections
      by enteric Campylobacter and Helicobacter were shown in 53.9% of group A and in
      5.0 % of group B. Our results show that both microorganisms commonly infect
      poultry, especially intensive farming animals. Only hooded crows among the wild
      bird group (group C), proved to be highly sensitive to Campylobacter infection.

PMID- 20814862
TI  - [Severe inflammation of the muzzle caused by a nose ring in a breeding bull].
AB  - This report describes the findings in a bull with severe inflammation of the
      muzzle and nose attributable to a nose ring. The most striking finding was that
      the bull continually licked the right side of the upper lip. The muzzle and right
      upper lip were swollen, hard, reddened and partially depigmented. Mucopurulent
      nasal discharge and salivation were also noted, and palpation of the right upper
      lip was extremely painful. Based on the findings, purulent infection of the right
      side of the muzzle, right naris and external nasal passage was diagnosed. After
      removing the nose ring the affected areas were washed daily for four days with a
      camomile-containing solution after which a chlorhexidine and dexpanthenol salve
      was applied. The bull also received ceftiofur and ketoprofen. The general
      condition and appetite of the bull normalised within a few days, and the
      inflammatory lesions resolved with the exception of the areas of depigmentation.
      After ten days of treatment, the bull was considered healthy and discharged from
      the clinic.

PMID- 20814866
TI  - [Conclusion of work relations].

PMID- 20814867
TI  - [Veterinary medicine societies have fused. The roads that begin from this are
      whatever people give them (Franz Kafka)].

PMID- 20814869
TI  - Analysis of peptides and proteins in their binding to GroEL.
AB  - The GroEL-GroES is an essential molecular chaperon system that assists protein
      folding in cell. Binding of various substrate proteins to GroEL is one of the key
      aspects in GroEL-assisted protein folding. Small peptides may mimic segments of
      the substrate proteins in contact with GroEL and allow detailed structural
      analysis of the interactions. A model peptide SBP has been shown to bind to a
      region in GroEL that is important for binding of substrate proteins. Here, we
      investigated whether the observed GroEL-SBP interaction represented those of
      GroEL-substrate proteins, and whether SBP was able to mimic various aspects of
      substrate proteins in GroE-assisted protein folding cycle. We found that SBP
      competed with substrate proteins, including alpha-lactalbumin, rhodanese, and
      malate dehydrogenase, in binding to GroEL. SBP stimulated GroEL ATP hydrolysis
      rate in a manner similar to that of alpha-lactalbumin. SBP did not prevent GroES
      from binding to GroEL, and GroES association reduced the ATPase rates of
      GroEL/SBP and GroEL/alpha-lactalbumin to a comparable extent. Binding of both SBP
      and alpha-lactalbumin to apo GroEL was dominated by hydrophobic interaction.
      Interestingly, association of alpha-lactalbumin to GroEL/GroES was
      thermodynamically distinct from that to GroEL with reduced affinity and decreased
      contribution from hydrophobic interaction. However, SBP did not display such
      differential binding behaviors to apo GroEL and GroEL/GroES, likely due to the
      lack of a contiguous polypeptide chain that links all of the bound peptide
      fragments. Nevertheless, studies using peptides provide valuable information on
      the nature of GroEL-substrate protein interaction, which is central to understand
      the mechanism of GroEL-assisted protein folding.

PMID- 20814870
TI  - Introducing haptic capabilities to a bone-mounted robot for intra-operative
      surface scanning.
AB  - BACKGROUND: Bone-mounted robots for orthopaedic surgery are small, cost-effective
      and could reduce invasiveness. Preoperative planning requires imaging (e.g. X
      ray, CT, MRI) and a registration procedure, which introduces error. Accuracy
      might be improved by building an intraoperative anatomical model in the robot's
      own coordinate system, utilizing the rigid bone-robot connection. METHODS: Haptic
      capabilities were added to MBARS and user tests were conducted to help design the
      haptic control loop. The accuracy of a 3D physical scan was tested on a femur
      model. RESULTS: Indication for force scaling and mode switching was found.
      Average distance error of collected points from the surface scanned by the robot
      was 0.3 mm. CONCLUSIONS: It is suggested that haptic control of bone-mounted
      robots should be non-linear and not necessarily transparent. Haptic surface
      acquisition can be used to generate an accurate intraoperative model of a joint
      surface.

PMID- 20814871
TI  - Functional assessment of a surgical robot for reduction of lower limb fractures.
AB  - BACKGROUND: This paper presents a novel robot designed for reduction of lower
      limb fractures, with the additional features of automatic controlled flexion of
      the knee joint, individual traction of thigh and leg, and foot rotation. The aim
      of this design is to assist the orthopaedic surgeon to perform better fracture
      reduction through motor control, in contrast to current manual control, and the
      results of assessments of its functions on normal subjects are presented in this
      paper. METHODS: The robot was designed to be mounted onto the operation table,
      and was controlled through open switch relay. Functional assessments were
      conducted on six healthy volunteers in terms of knee joint motion and lower limb
      traction; measurement of angle and distance was calculated from data obtained by
      a 3D ultrasonic motion system (Zebris((r)) ). RESULTS: The results showed a good
      correlation of the flexion angle between the robot and the subjects at the knee
      joint. In the traction tests, a steady lengthening of the proximal as well as the
      distal segment of the robot was observed, and a slight increase in subjects' limb
      length was also recorded, which might be due to distraction in the joint space.
      CONCLUSION: This automatic control fracture table has distinct features compared
      with the conventional ones, and it is believed to be of assistance to surgeons
      when performing fracture fixations.

PMID- 20814872
TI  - Intrapartum translabial three-dimensional ultrasound visualization of levator
      trauma.
AB  - OBJECTIVES: The aim of this study was to visualize levator trauma by three
      dimensional (3D) ultrasound performed during labor and soon after the crowning of
      the fetal head and to determine how often levator trauma occurs. METHODS: This
      was a prospective, observational study of 66 women enrolled during the first
      stage of labor. The women underwent intrapartum 3D transperineal ultrasound
      examination during the first and second stages of labor and within 12 h after
      delivery. Volume datasets were acquired and analyzed to determine the presence of
      levator trauma. RESULTS: Data from 10 of the 66 women were excluded from analysis
      nine because they underwent Cesarean section in the first or second stage of
      labor and one because she underwent hysterectomy and no postpartum volumes were
      collected. Thus our study group comprised 56 women-35 nulliparous and 21 parous.
      A total of 504 volumes were collected in the 56 women (three volumes for each
      stage of labor). One hundred and twenty levator volumes were excluded from
      analysis, but volumes of acceptable quality were available for all three stages
      of labor in all women. Eleven (31.4%) of the 35 nulliparae had levator lesions
      detected postpartum and none of them had levator lesions before delivery. Five
      (23.8%) of the 21 parous women had a levator tear detected in their postpartum
      volumes. In two of these five women the levator tear was also present in both
      volumes taken during labor. CONCLUSIONS: Visualization of the levator ani during
      labor by 3D ultrasound examination is feasible. Comparison of volumes obtained
      during labor and within the first 2 h after delivery supports the theory that
      crowning of the head is the immediate cause of avulsion of the levator ani
      muscle.

PMID- 20814873
TI  - Semi-automated adjusted measurement of nuchal translucency: feasibility and
      reproducibility.
AB  - OBJECTIVE: The variability of nuchal translucency thickness (NT) measurements in
      the first trimester appears to be associated in part with caliper placement.
      Methods for obtaining semi-automated adjusted measurements (SAAMs) can provide
      several NT values (maximum, minimum, mean and median) automatically within a
      manually set frame in the zone of interest. This study sought to assess the
      feasibility and reproducibility of these SAAM-NTs. METHODS: Three readers, two
      experts and one less experienced, examined archive images of 160 patients and
      obtained SAAM-NTs from them, on two separate occasions. The intra- and
      interobserver reproducibility were assessed by calculating the intraclass
      correlation coefficients (ICCs) for maximum, mean and median SAAM-NTs, and Bland
      Altman plots were constructed. RESULTS: SAAM-NTs were technically feasible for
      all 160 images. The range of ICCs for intraobserver reproducibility was 0.76-0.93
      for mean SAAM-NT, 0.76-0.95 for median SAAM-NT and 0.74-0.95 for maximum SAAM-NT.
      Interobserver ICCs were 0.85, 0.85 and 0.84 for mean SAAM-NT, median SAAM-NT and
      maximum SAAM-NT, respectively. There were no significant differences for intra-
      and interobserver reproducibility of median, mean and maximum SAAM-NTs.
      CONCLUSIONS: SAAM-NT is feasible with a high level of intra- and interobserver
      reproducibility. This easy-to-use method has the potential to simplify screening
      during the first trimester. It should be evaluated further and compared with the
      manual measurement method.

PMID- 20814874
TI  - State of the art: an integrated approach to pelvic floor ultrasonography.
AB  - Surgical management of pelvic floor disorders depends on a comprehensive
      understanding of the structural integrity and function of the pelvic floor. For
      visualizing this region, ultrasonography has emerged as a procedure that is
      relatively easy to perform, cost-effective and widely available. In this review,
      pelvic floor ultrasonography, including two-dimensional (2D), three-dimensional
      (3D) and 4D imaging as well as transvaginal, endoanal and transperineal
      techniques, is discussed from a global and multicompartmental perspective, rather
      than using a compartmentalized approach. The role of the different sonographic
      modalities in the major disorders of the pelvic floor-urinary and fecal
      incontinence, pelvic organ prolapse and obstructed defecation syndrome-is
      evaluated critically.

PMID- 20814875
TI  - Temporal and spatial performance of vector velocity imaging in the human fetal
      heart.
AB  - OBJECTIVES: To assess the spatial and temporal performance of fetal myocardial
      speckle tracking, using high-frame-rate (HFR) storing and Lagrangian strain
      analysis. METHODS: Dummy electrocardiographic signaling permitted DICOM HFR in
      124 normal fetuses and paired low-frame-rate (LFR) video storing at 25 Hz in 93
      of them. Vector velocity imaging (VVI) tracking co-ordinates were used to compare
      time and spatial domain measures. We compared tracking success, Lagrangian
      strain, peak diastolic velocity and positive strain rate values in HFR vs. LFR
      video storing. Further comparisons within an HFR subset included Lagrangian vs.
      natural strain, VVI vs. M-mode annular displacement, and VVI vs. pulsed-wave
      tissue Doppler imaging (TDI) peak velocities. RESULTS: HFR (average 79.4 Hz)
      tracking was more successful than LFR (86 vs. 76%, P = 0.024). Lagrangian and
      natural HFR strain correlated highly (left ventricle (LV): r = 0.883, P < 0.001;
      right ventricle (RV): r = 0.792, P < 0.001) but natural strain gave 20% lower
      values, suggesting reduced reliability of measurement. Lagrangian HFR strain was
      similar in LV and RV and decreased with gestation (P = 0.015 and P < 0.001,
      respectively). LV Lagrangian LFR strain was significantly lower than the values
      for the RV (P < 0.001) and those using paired LV-HFR recordings (P = 0.007).
      Annular displacement methods correlated highly (LV = 1.046, r = 0.90, P < 0.001;
      RV = 1.170, r = 0.88, P < 0.001). Early diastolic waves were visible in 95% of
      TDI, but in only 26% of HFR and 0% of LFR recordings, and HFR-VVI velocities were
      significantly lower than those for TDI (P < 0.001). CONCLUSIONS: Doppler
      estimation of velocities remains superior to VVI but image gating and use of
      original co-ordinates should improve offline VVI assessment of fetal myocardial
      function.

PMID- 20814876
TI  - Defining the fetal cardiac axis between 11 + 0 and 14 + 6 weeks of gestation:
      experience with 100 consecutive pregnancies.
AB  - OBJECTIVE: The purpose of this study was to establish normal fetal cardiac axis
      values during the first and early second trimesters of pregnancy. METHODS: This
      was a prospective observational cohort study in which the fetal cardiac axis was
      assessed during ultrasound examinations in 100 consecutive fetuses between 11 + 0
      and 14 + 6 weeks of gestation. Transabdominal, and, when indicated, transvaginal,
      approaches were used. Intraobserver and interobserver reproducibility were
      calculated. RESULTS: The cardiac axis ranged from 34.5 to 56.8 degrees  (mean
      (SD) 47.6 +/- 5.6 degrees ) in 94 fetuses with normal cardiac anatomy. The fetal
      cardiac axis tended to be significantly higher in fetuses at 11 + 0 to 11 + 6
      weeks of gestation than in fetuses at 12 + 0 to 14 + 6 weeks of gestation.
      Congenital heart defects were found in six out of 100 fetuses, four of which had
      abnormal cardiac axis values at 11 + 0 to 14 + 6 weeks of gestation. CONCLUSION:
      Cardiac axis measurement is possible in the first and early second trimesters of
      pregnancy. The assessment of cardiac axis at an early gestational age may help to
      identify pregnancies at high risk for congenital heart defects. Copyright

PMID- 20814877
TI  - Accuracy of fetal gender determination in the first trimester using three
      dimensional ultrasound.
AB  - OBJECTIVES: To evaluate the accuracy of three-dimensional (3D) ultrasound in
      fetal gender assignment in the first trimester. METHODS: A series of pregnant
      women attending at 11 to 13 + 6 weeks for the nuchal translucency (NT) scan were
      enrolled into the study. An ultrasound volume of each fetus was obtained and
      stored for offline analysis. On the reconstructed mid-sagittal plane, the angle
      between the genital tubercle and an imaginary line passing tangentially through
      the fetal back (genital angle) was estimated and a receiver-operating
      characteristics (ROC) curve was constructed to determine the best cut-off for
      genital angle in fetal male gender determination. Fetal gender was subsequently
      ascertained in all cases. To calculate the interobserver variability, a second
      operator repeated the measurements. RESULTS: There were 85 cases included in the
      study. The genital angle in males was significantly higher than that in females
      (51.2 +/- 11.3 degrees  (n = 36) vs. 18.9 +/- 4.1 (n = 49), P < 0.001). The ROC
      curve revealed the estimated genital angle to have a high degree of accuracy in
      fetal gender determination (area under the curve +/- SE = 1.000 +/- 0.001). The
      best cut-off for male gender determination was found to be between 27 degrees 
      and 29 degrees  (sensitivity, 100%; specificity, 98.0%). There was a high degree
      of correlation between the two operators (r(2) = 0.998; coefficient of variation
      = 5.4%). CONCLUSIONS: 3D ultrasound is a highly accurate and reproducible tool
      for fetal gender assignment prior to 14 weeks of gestation.

PMID- 20814878
TI  - Improving the preoperative classification of adnexal masses as benign or
      malignant by second-stage tests.
AB  - OBJECTIVE: The aim of this study was to establish when a second-stage diagnostic
      test may be of value in cases where a primary diagnostic test has given an
      uncertain diagnosis of the benign or malignant nature of an adnexal mass.
      METHODS: The diagnostic performance with regard to discrimination between benign
      and malignant adnexal masses for mathematical models including ultrasound
      variables and for subjective evaluation of ultrasound findings by an experienced
      ultrasound examiner was expressed as area under the receiver-operating
      characteristics curve (AUC), sensitivity and specificity. These were calculated
      for the total study population of 1938 patients with an adnexal mass as well as
      for subpopulations defined by the certainty with which the diagnosis of benignity
      or malignancy was made. The effect of applying a second-stage test to the tumors
      where risk estimation was uncertain was determined. RESULTS: The best
      mathematical model (LR1) had an AUC of 0.95, sensitivity of 92% and specificity
      of 84% when applied to all tumors. When model LR1 was applied to the 10% of
      tumors in which the calculated risk fell closest to the risk cut-off of the
      model, the AUC was 0.59, sensitivity 90% and specificity 21%. A strategy where
      subjective evaluation was used to classify these 10% of tumors for which LR1
      performed poorly and where LR1 was used in the other 90% of tumors resulted in a
      sensitivity of 91% and specificity of 90%. Applying subjective evaluation to all
      tumors yielded an AUC of 0.95, sensitivity of 90% and specificity of 93%.
      Sensitivity was 81% and specificity 47% for those patients where the ultrasound
      examiner was uncertain about the diagnosis (n = 115; 5.9%). No mathematical model
      performed better than did subjective evaluation among the 115 tumors where the
      ultrasound examiner was uncertain. CONCLUSION: When model LR1 is used as a
      primary test for discriminating between benign and malignant adnexal masses, the
      use of subjective evaluation of ultrasound findings by an experienced examiner as
      a second-stage test in the 10% of cases for which the model yields a risk of
      malignancy closest to its risk cut-off will improve specificity without
      substantially decreasing sensitivity. However, none of the models tested proved
      suitable as a second-stage test in tumors where subjective evaluation yielded an
      uncertain result.

PMID- 20814879
TI  - Likelihood ratio-based quality control for nuchal translucency measurements at 11
      14 weeks of gestation.
AB  - OBJECTIVE: To develop a quantitative quality control process of nuchal
      translucency (NT) measurement at 11-14 weeks of gestation based on the mixture
      model, characterized by analysis of the corresponding distribution of the
      likelihood ratio (LR). METHODS: Based on the published mixture model for NT
      measurement in the first trimester, we simulated the expected distribution of NT
      and the corresponding LR. This approach was then tested for the quality control
      of 15 048 NT measurements performed by four operators trained and certified by
      The Fetal Medicine Foundation. The new quality control approach based on LR was
      compared with existing processes based on NT plots, multiples of the median
      (MoMs) and analysis of the 95(th) centile. RESULTS: Each operator contributed
      2176-4730 examinations. Median, 5(th) and 95(th) centile of NT values ranged from
      1.4 to 1.6, 1.0 to 1.0 and 2.2 to 2.6 mm, respectively. Median of NT-MoM values
      ranged from 0.83 to 0.95. Analysis of the distribution of NT measurements
      confirmed departure from the assumptions of the delta-NT and NT-MoM models.
      Analysis of LR distributions demonstrated a significant difference between
      observed and expected distributions for all operators (P < 10(-4) ). CONCLUSION:
      An LR-based quality control process is feasible at 11-14 weeks of gestation.
      Because it is more sensitive to measurement bias around the critical area of the
      95(th) centile, its use should be encouraged.

PMID- 20814880
TI  - An intron in the cytochrome b gene of Monilinia fructicola mitigates the risk of
      resistance development to QoI fungicides.
AB  - BACKGROUND: The cytochrome b (Cyt b) gene is a key genetic determinant for
      quinone outside inhibitor (QoI) fungicide resistance in plant pathogenic fungi. A
      mutation at amino acid position G143 can cause qualitative resistance unless it
      is part of the recognition site for a self-splicing intron. The objective of this
      study was to clone and sequence the Cyt b gene from Monilinia fructicola (Wint.)
      Honey, the causal agent of brown rot of stone fruits, and to assess the risk for
      the development of a mutation at position 143. RESULTS: The Cyt b gene of M.
      fructicola was 11 927 bp in size and contained seven introns located at cDNA
      positions (5'-3') 204, 395, 430, 491, 507, 780 and 812 with sizes of 1592, 1318,
      1166, 1252, 1065, 2131 and 2227 bp respectively. Sequence analysis revealed that
      the above-mentioned 1166 bp intron, a self-splicing group I intron, was located
      just downstream of the G143 codon. The Cyt b gene region covering the G143
      location and the adjacent 1166 bp intron was PCR amplified and sequenced from
      Chinese and US isolates, indicating that the intron may be omnipresent in M.
      fructicola. CONCLUSION: This is the first complete Cyt b gene sequence published
      for M. fructicola or any other Monilinia species, forming the basis for molecular
      analysis of QoI fungicide resistance. Sequence analysis revealed that the G143A
      mutation responsible for high levels of QoI fungicide resistance in many plant
      pathogenic fungi may not develop in M. fructicola unless genotypes emerge that
      lack the 1166 bp intron.

PMID- 20814881
TI  - Nutrition facts and functional potential of quinoa (Chenopodium quinoa willd.),
      an ancient Andean grain: a review.
AB  - Quinoa, Chenopodium quinoa Willd., is an Amaranthacean, stress-tolerant plant
      cultivated along the Andes for the last 7000 years, challenging highly different
      environmental conditions ranging from Bolivia, up to 4.500 m of altitude, to sea
      level, in Chile. Its grains have higher nutritive value than traditional cereals
      and it is a promising worldwide cultivar for human consumption and nutrition. The
      quinoa has been called a pseudo-cereal for botanical reasons but also because of
      its unusual composition and exceptional balance between oil, protein and fat. The
      quinoa is an excellent example of 'functional food' that aims at lowering the
      risk of various diseases. Functional properties are given also by minerals,
      vitamins, fatty acids and antioxidants that can make a strong contribution to
      human nutrition, particularly to protect cell membranes, with proven good results
      in brain neuronal functions. Its minerals work as cofactors in antioxidant
      enzymes, adding higher value to its rich proteins. Quinoa also contains
      phytohormones, which offer an advantage over other plant foods for human
      nutrition.

PMID- 20814882
TI  - Effect of storage conditions on sensory properties of Bierzo roasted pepper.
AB  - BACKGROUND: Roasted pepper is marketed with the European recognition of Protected
      Geographical Indication 'Pimiento Asado del Bierzo'. The industry needs to
      prolong the period in which fresh pepper received from farmers is available to be
      processed, without deteriorating the sensory quality of roasted pepper. The
      objective of this study was to analyse how different storage conditions affect
      the sensory quality of roasted pepper. RESULTS: Differences in weight loss among
      storage conditions did not affect roast yield. Descriptors juice quality,
      bitterness and spiciness were not influenced by storage conditions in 2006 or
      2007, whereas uniformity, skin surface, cohesiveness and smokiness were
      influenced by storage conditions in both years. Overall quality was better when
      pepper was stored for 5 days at 18  degrees C or for 10 days at 8  degrees C.
      CONCLUSION: The quality of roasted pepper was affected positively by storage
      conditions in terms of colour and uniformity, which were improved, and hardness,
      which was reduced. Newly roasted samples, on the other hand, obtained the lowest
      quality values. Therefore storage of pepper for up to 10 days was useful not only
      to extend the time of roasted pepper processing for companies but also to improve
      the sensory quality of roasted pepper without decreasing the roast yield of
      processed pepper.

PMID- 20814883
TI  - Effect of storage on chemical and sensory profiles of peanut pastes prepared with
      high-oleic and normal peanuts.
AB  - BACKGROUND: Peanut paste and peanut butter have high oil contents and are thus
      susceptible to developing rancidity and off-flavours through lipid oxidation.
      Preservation of the chemical and sensory quality of these products is one of the
      main problems in the peanut industry. The purpose of this study was to compare
      the chemical and sensory stability of peanut paste prepared with high-oleic
      peanuts (cv. Granoleico, GO-P) with that of peanut paste prepared with normal
      peanuts (cv. Tegua, T-P) from Argentina. RESULTS: Chemical (peroxide and p
      anisidine values and conjugated dienes) and sensory (roasted peanutty, oxidised
      and cardboard flavours) indicators of lipid oxidation were measured in peanut
      pastes stored at 4, 23 and 40  degrees C. Chemical indicator values and oxidised
      and cardboard flavours showed lower increments in GO-P than in T-P during
      storage. T-P had significantly higher peroxide value than GO-P. Roasted peanutty
      flavour showed a lower decrease in GO-P. Peanut paste prepared with high-oleic
      peanuts had four (at 4  degrees C), two (at 23  degrees C) and three (at 40 
      degrees C) times longer shelf-life than peanut paste prepared with normal
      peanuts. CONCLUSION: These results indicate that high-oleic Granoleico kernels
      provide peanut paste with higher protection against lipid oxidation.

PMID- 20814884
TI  - The snake venom peptide Bj-PRO-7a is a M1 muscarinic acetylcholine receptor
      agonist.
AB  - Proline-rich peptides from Bothrops jararaca venom (Bj-PRO) were characterized
      based on the capability to inhibit the somatic angiotensin-converting enzyme. The
      pharmacological action of these peptides resulted in the development of
      Captopril, one of the best examples of a target-driven drug discovery for
      treatment of hypertension. However, biochemical and biological properties of Bj
      PROs were not completely elucidated yet, and many recent studies have suggested
      that their activity relies on angiotensin-converting enzyme-independent
      mechanisms. Here, we show that Bj-PRO-7a (<EDGPIPP) specifically activates
      [Ca(2+)](i) transients in CHO-M1 cells expressing heterologous rat M1 muscarinic
      subtype. The activation curve established by microfluorimetry in CHO-M1 cells
      using increasing concentrations of Bj-PRO-7a reached the maximum response in the
      presence of 3 MUM Bj-PRO-7a (EC(50) = 0.25 +/- 0.07 MUM). The variation observed
      by calcium imaging in these cells ranged from 52 to 1218 nM (EC(50) = 0.31 +/-
      0.12 MUM). [Ca(2+)](i) responses in CHO-M1 cells were largely inhibited by
      pirenzepine, a specific M1 antagonist. Neural-differentiated P19 cells expressing
      endogenous M1 receptors were also responsive to Bj-PRO-7a application, whereas no
      such response was observed in undifferentiated P19 cells not expressing
      muscarinic receptors. As further support for its specific action on M1 receptors,
      the peptide did not activate M3 subtypes in transfected CHO cells. Our findings
      provide a novel M1 muscarinic receptor agonist that could be used for basic
      research and even for pharmacological applications.

PMID- 20814885
TI  - Synthesis and proteasome inhibition of N-allyl vinyl ester-based peptides.
AB  - Inhibition of the proteasome, the multicatalytic protease complex responsible for
      the turnover of many cellular proteins, represents an attractive target in the
      development of new drug therapies, proteasome inhibitors being potentially useful
      tools for the treatment of pathologies such as cancer, as well as inflammatory,
      immune and neurodegenerative diseases. Based on our previous development of a new
      class of inhibitors bearing a C-terminal VE cluster able to interact with
      catalytic threonine, we report herein the synthesis and activity of new VE-based
      peptide analogs bearing an additional allyl pharmacophore unit at the C- or N
      terminal position of the pseudotripeptide sequence. In the new series, the
      structural modification carried out to the prototype determine a decrease of
      proteasome inhibition.

PMID- 20814886
TI  - Correlation of product ion profiles with molecular structures of androgenic and
      anabolic steroids in ESI MS/MS.
AB  - Androgenic and anabolic steroids (AASs) are a class of chemical substances
      closely related to testosterone in molecular structure. They can be abused to
      enhance performances in human and equine athletes, and are banned by the sports
      authorities. To assist with method development for doping analyses of AASs,
      investigations were conducted to correlate their product ion profiles with the
      molecular structures. Although very similar in chemical structure, AASs generated
      noticeably different product ion profiles from collision-induced dissociation
      (CID). On the basis of both outlines of the product ion profiles and molecular
      structures, AASs studied were classified into six subclasses. In each subclass,
      the product ion profiles were identical or similar. However, the product ion
      profiles in one subclass were remarkably different from those in another. The
      classification reveals that the position and number of double bond(s) in
      conjugation with the 3-carbonyl group in the molecular structure of an AAS have
      significant effects on product ion profile. The presence or absence of the 19
      methyl group in an AAS also has a remarkable influence on its product ion
      profile. A substitution in the A-, B- or D-ring of an AAS may cause a shift in
      mass value of the product ions. The correlation of product ion profiles with
      molecular structures of AASs has the implication that each AAS can be
      characterized by a combination of its [M + H](+) ion and product ion profile and
      as a result be identified with specificity. The classified product ion pattern
      may be useful in the identification of unknown AASs.

PMID- 20814887
TI  - Competitive mass spectrometry binding assay for characterization of three binding
      sites of tubulin.
AB  - Tubulin is an attractive and established target for anticancer therapy. To date,
      the only method to determine the binding of inhibitor to tubulin has been
      competitive radioligand binding assays. We developed a non-radioactive mass
      spectrometry (MS) binding assay to study the tubulin binding of colchicine,
      vinblastine and paclitaxel and to identify which of these three binding sites
      that a novel inhibitor binds. The method involves a very simple step of
      separating the unbound ligand from macromolecules using ultrafiltration. The
      unbound ligand in the filtrate can be accurately determined using highly
      sensitive and specific liquid chromatography tandem mass spectrometry (LC-MS/MS)
      method using multiple reaction monitoring (MRM) mode. The assay was validated
      using podophyllotoxin, vincristine and docetaxel, drugs that compete to the
      colchicine-, vinblastine- and paclitaxel-binding sites in tubulin, respectively.
      This competitive binding assay allowed the reliable detection of interactions of
      these drugs with three binding sites on tubulin. This method was subsequently
      applied to determine the tubulin-binding site of 4-substituted methoxylbenzoyl
      aryl-thiazoles (SMART-H), a potent antitubulin agent developed in our laboratory.
      The results indicated that SMART-H specifically and reversibly bound only to the
      colchicine-binding site, but not to vinblastine- or paclitaxel sites. This new
      non-radioligand binding method to determine the binding site on tubulin will
      function as a useful tool to study the binding sites of tubulin inhibitors.

PMID- 20814888
TI  - Probing protein function by chemical modification.
AB  - Labeling proteins with synthetic probes, such as fluorophores, affinity tags, and
      other functional labels is enormously useful for characterizing protein function
      in vitro, in live cells, or in whole organisms. Recent advancements of chemical
      methods have substantially expanded the tools that are applicable to modify
      proteins. In this review, we discuss some important chemical methods for site
      specific protein modification and highlight the application of established
      techniques to tackle biological questions.

PMID- 20814889
TI  - Interactions of amyloid Abeta(1-42) peptide with self-assembled peptide
      nanospheres.
AB  - In this work we have probed the interactions of the amyloid Abeta(1-42) peptide
      with self-assembled nanospheres. The nanospheres were formed by self-assembly of
      a newly developed bolaamphiphile bis(N-alpha-amido-methionine)-1,8 octane
      dicarboxylate under aqueous conditions. It was found that the interactions of the
      Abeta(1-42) peptide with the nanospheres were concentration as well as pH
      dependent and the peptide largely adopts a random coil structure upon interacting
      with the nanospheres. Further, upon incorporation with the nanospheres, we
      observed a relative diminution in the aggregation of Abeta(1-42) at low
      concentrations of Abeta(1-42). The interactions between the nanospheres and the
      Abeta(1-42) peptide were investigated by atomic force microscopy, transmission
      electron microscopy, circular dichroism, FTIR and fluorescence spectroscopy, and
      the degree of fibrillation in the presence and absence of nanospheres was
      monitored by the Thioflavine T assay. We believe that the outcome from this work
      will help further elucidate the binding properties of Abeta peptide as well as
      designing nanostructures as templates for further investigating the nucleation
      and fibrillation process of Abeta-like peptides.

PMID- 20814890
TI  - Nanopore analysis of tethered peptides.
AB  - Peptides of 12 amino acids were tethered via a terminal cysteine to mono-, di-,
      tri-, and tetrabromomethyl-substituted benzene to produce bundles of one to four
      peptide strands (CY12-T1 to CY12-T4, respectively). The interaction of the
      bundles with the alpha-hemolysin pore was assessed by measuring the blockade
      currents (I) and times (T) at an applied potential of - 50, - 100, and - 150 mV.
      Three types of events could be distinguished: bumping events, with small I and
      short T where the molecule transiently interacts with the pore before diffusing
      away; translocation events, where the molecule threads through the pore with
      large I and the value of T decreases with increasing voltage; and intercalation
      events, where the molecule transiently enters the pore but does not translocate
      with large I and the value of T increases with increasing voltage. CY12-T1 and
      CY12-T2 gave only bumping and translocation events; CY12-T3 and CY12-T4 also gave
      intercalation events, some of which were of very long duration. The results
      suggest that three uncoiled peptide strands cannot simultaneously thread through
      the alpha-hemolysin pore and that proteins must completely unfold in order to
      translocate.

PMID- 20814891
TI  - Single cell phospho-specific flow cytometry can detect dynamic changes of phospho
      Stat1 level in lung cancer cells.
AB  - Single cell phospho-specific flow cytometry (SCPFC) enables the investigation of
      signaling network interactions and the categorization of disease outcome. While
      this method has been successfully used to study hematologic disorders, its
      application on solid tumors has not been examined. This study aimed to
      demonstrate the ability of SCPFC to detect dynamic changes of Tyrosine phospho
      Stat1 (pStat1) in solid tumor models and in human tumor samples. In the human
      lung cancer cell line PC14PE6/AS2, the fluorescence intensity changes of pStat1
      after IFN-gamma stimulation were compatible to results obtained by Western blot
      analysis. In metastatic animal models, cancer cells from subcutaneous tumors,
      malignant ascites, and peritoneal tumors responded to IFN-gamma. The pStat1 was
      activated in these cells after IFN-gamma stimulation, with a 1.5- to 2.5-fold
      increase in fluorescence intensity compared to the unstimulated control. To
      examine the potential clinical application of SCPFC, cancer cells were collected
      from malignant pleural effusions (MPEs) of lung cancer patients to observe the
      activation of pStat1 after IFN-gamma stimulation. Cell apoptosis after cisplatin
      treatment was evaluated by Annexin V staining, which showed that MPE cancer cells
      with higher pStat1 changes after IFN-gamma stimulation were more resistant to
      cisplatin. In conclusion, there is a preliminary application of SCPFC to solid
      tumors and links to drug sensitivity are promising.

PMID- 20814892
TI  - Smoking is associated with histological severity in nonalcoholic steatohepatitis.

PMID- 20814893
TI  - Is this really the end of beta-blockers in patients with cirrhosis and refractory
      ascites?

PMID- 20814894
TI  - Drug therapy: rifaximin.

PMID- 20814895
TI  - Fructose at the center of necroinflammation and fibrosis in nonalcoholic
      steatohepatitis.

PMID- 20814896
TI  - A phase 1/2, dose-escalation trial of deferasirox for the treatment of iron
      overload in HFE-related hereditary hemochromatosis.
AB  - Hereditary hemochromatosis (HH) is characterized by increased intestinal iron
      absorption that may result in iron overload. Although phlebotomy is widely
      practiced, it is poorly tolerated or contraindicated in patients with anemias,
      severe heart disease, or poor venous access, and compliance can vary. The once
      daily, oral iron chelator, deferasirox (Exjade) may provide an alternative
      treatment option. Patients with HH carrying the HFE gene who were homozygous for
      the Cys282Tyr mutation, serum ferritin levels of 300-2000 ng/mL, transferrin
      saturation >= 45%, and no known history of cirrhosis were enrolled in this dose
      escalation study to characterize the safety and efficacy of deferasirox,
      comprising a core and an extension phase (each 24 weeks). Forty-nine patients
      were enrolled and received starting deferasirox doses of 5 (n = 11), 10 (n = 15),
      or 15 (n = 23) mg/kg/day. Adverse events were generally dose-dependent, the most
      common being diarrhea, headache, and nausea (n = 18, n = 10, and n = 8 in the
      core and n = 1, n = 1, and n = 0 in the extension, respectively). More patients
      in the 15 mg/kg/day than in the 5 or 10 mg/kg/day cohorts experienced increases
      in alanine aminotransferase and serum creatinine levels during the 48-week
      treatment period; six patients had alanine aminotransferase > 3 * baseline and
      greater than the upper limit of normal range, and eight patients had serum
      creatinine > 33% above baseline and greater than upper limit of normal on two
      consecutive occasions. After receiving deferasirox for 48 weeks, median serum
      ferritin levels decreased by 63.5%, 74.8%, and 74.1% in the 5, 10, and 15
      mg/kg/day cohorts, respectively. In all cohorts, median serum ferritin decreased
      to < 250 ng/mL. CONCLUSION: Deferasirox doses of 5, 10, and 15 mg/kg/day can
      reduce iron burden in patients with HH. Based on the safety and efficacy results,
      starting deferasirox at 10 mg/kg/day appears to be most appropriate for further
      study in this patient population.

PMID- 20814897
TI  - Hepatitis B virus-DNA level and basal core promoter A1762T/G1764A mutation in
      liver tissue independently predict postoperative survival in hepatocellular
      carcinoma.
AB  - Hepatitis B virus (HBV) is a major etiological factor of hepatocellular carcinoma
      (HCC). However, the postoperative prognostic value of the virological factors
      assayed directly from liver tissue has never been investigated. To address this
      issue, 185 liver samples obtained from the noncancerous part of surgically
      removed HBV-associated HCC tissues were subjected to virological analysis.
      Assayed factors included the amount of HBV-DNA in the liver tissues; genotype;
      and the presence of the HBV precore stop codon G1896A mutation, basal core
      promoter A1762T/G1764A mutation, and pre-S deletions/stop codon mutation. All
      virological factors and clinicopathological factors were subjected to Cox
      proportional hazard model analysis to estimate postoperative survival. It was
      found that an HBV-DNA level >3.0 * 10(7) copies/g of liver tissue and the
      presence of the basal core promoter mutation independently predicted disease-free
      (adjusted hazard ratio 1.641 [95% confidence interval (CI) 1.010-2.667] and 2.075
      [95% CI 1.203-3.579], respectively) and overall (adjusted hazard ratio 2.807 [95%
      CI 1.000-7.880] and 5.697 [95% CI 1.678-19.342], respectively) survival. Kaplan
      Meier survival analysis indicated that in-frame, short stretch (<100 bp) pre-S
      deletions, but not large fragment (>100 bp) pre-S deletions, were significantly
      associated with poorer disease-free (P = 0.005) and overall (P = 0.020) survival.
      A hot deletion region located between codons 107 and 141 of the pre-S sequence
      was identified for the short stretch pre-S deletion mutants. CONCLUSION: The
      amount of HBV-DNA in liver tissue and the presence of the basal core promoter
      mutation were two independent predictors for postoperative survival in HCC. A
      short stretch pre-S deletion located between codons 107 and 141 was strongly
      associated with a poorer postoperative prognosis.

PMID- 20814898
TI  - Retrograde salvage approach to treat tibial artery perforation during attempted
      revascularization of a chronically occluded artery.
AB  - Arterial perforation is a well-recognized complication of attempted percutaneous
      revascularization of a chronic totally occluded tibial artery and typically
      necessitates termination of the procedure. This report describes a step-by-step
      approach on how to perform a direct posterior tibial artery puncture and a
      sheathless wire introduction, to salvage a case of tibial artery perforation
      induced during attempted anterograde recanalization of an occluded tibial artery.
      After control of blood loss, retrograde wire passage and balloon inflation can
      facilitate relocation of the anterograde wire in the true lumen allowing
      uneventful completion of the procedure. (c) 2010 Wiley-Liss, Inc.

PMID- 20814899
TI  - Covered stent to treat saphenous venous graft perforation--a case report.
AB  - This case report shows the immediate and long-term clinical result of
      percutaneous coronary intervention in a patient with total occlusion of saphenous
      venous graft. The case also highlights the management of venous graft perforation
      during percutaneous intervention using a covered stent.

PMID- 20814900
TI  - Endostatin inhibits tumour lymphangiogenesis and lymphatic metastasis via cell
      surface nucleolin on lymphangiogenic endothelial cells.
AB  - Endostatin has potent anti-endothelial and anti-angiogenic functions. Endostatin
      was reported to reduce lymphangiogenesis by down-regulating the level of VEGF-C
      in tumour tissues. However, there is little evidence for the direct function of
      endostatin on lymphangiogenic endothelial cells and lymphangiogenic vessels.
      Here, we report that cell surface nucleolin, which was reported as an endostatin
      receptor mediating its anti-angiogenic and anti-tumour functions, is also
      selectively expressed on the cell surface of lymphangiogenic endothelial cells
      both in vitro and in vivo. Treatment of primary mouse lymphatic endothelial cells
      (mLECs) by endostatin inhibits mLEC migration, tubule formation, and activation
      of the Erk pathway in mLECs, while neutralization of cell surface nucleolin or
      nucleolin knockdown results in loss of the anti-lymphatic endothelial activities
      of endostatin. Also, anti-nucleolin antibody or lentivirus delivered nucleolin
      siRNA abolishes the anti-lymphangiogenic function of endostatin in the Matrigel
      plug assay. Endostatin remarkably inhibits tumour-associated lymphangiogenesis,
      leading to reduced lymphatic metastasis. Systemic blockade of nucleolin notably
      abolishes the anti-lymphangiogenic and anti-lymphatic metastatic functions of
      endostatin. Importantly, endostatin does not affect quiescent lymphatics in
      normal organs, which is consistent with the lack of expression of cell surface
      nucleolin in quiescent lymphatics. Taken together, our results demonstrate that
      endostatin directly acts on lymphangiogenic endothelial cells via cell surface
      nucleolin, which provides a novel mechanism for the inhibition of tumour
      lymphangiogenesis and lymphatic metastasis by endostatin.

PMID- 20814901
TI  - Oestrogen-induced epithelial-mesenchymal transition of endometrial epithelial
      cells contributes to the development of adenomyosis.
AB  - Adenomyosis is an oestrogen-dependent disease caused by a downward extension of
      the endometrium into the uterine myometrium. Epithelial-mesenchymal transition
      (EMT) endows cells with migratory and invasive properties and can be induced by
      oestrogen. We hypothesized that oestrogen-induced EMT is critical in the
      pathogenesis of adenomyosis. We first investigated whether EMT occurred in
      adenomyotic lesions and whether it correlated with serum 17beta-oestradiol (E2)
      levels. Immunohistochemistry was performed on adenomyotic lesions and
      corresponding eutopic endometrium samples from women with adenomyosis. Endometria
      from women without endometrial disorders were used as a control. In the
      epithelial component of adenomyotic lesions, vimentin expression was up-regulated
      and E-cadherin expression was down-regulated compared to the eutopic endometrium,
      suggesting that EMT occurs in adenomyosis. In adenomyosis, the serum E2 level was
      negatively correlated with E-cadherin expression in the epithelial components of
      the eutopic endometrium and adenomyotic lesions, suggesting the involvement of
      oestrogen-induced EMT in endometrial cells. In oestrogen receptor-positive
      Ishikawa endometrial epithelial cells, oestrogen induced a morphological change
      to a fibroblast-like phenotype, a shift from epithelial marker expression to
      mesenchymal marker expression, increased migration and invasion, and up
      regulation of the EMT regulator Slug. Raloxifene, a selective oestrogen receptor
      modulator, abrogated these effects. To determine the role of oestrogen-induced
      EMT in the implantation of ectopic endometrium, we xenotransplanted eutopic
      endometrium or adenomyotic lesions from adenomyosis patients into ovariectomized
      SCID mice. The implantation of endometrium was oestrogen-dependent and was
      suppressed by raloxifene. Collectively, these data highlight the crucial role of
      oestrogen-induced EMT in the development of adenomyosis and suggest that
      raloxifene may be a potential therapeutic agent for adenomyosis patients.

PMID- 20814903
TI  - Progressive renal distortion by multiple cysts in transgenic mice expressing
      artificial microRNAs against Pkd1.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common
      life-threatening inherited diseases, and the PKD1 gene is responsible for most
      cases of this disease. Previous efforts to establish a mouse model that
      recapitulates the phenotypic characteristics of ADPKD, which have used
      conventional or conditional knockout of the mouse orthologue Pkd1, have been
      unsuccessful or unreliable. In a previous study, we described the generation of a
      novel Pkd1 hypomorphic allele, in which Pkd1 expression was significantly reduced
      but not totally blocked. These Pkd1 homozygous mutant mice rapidly developed
      renal cystic disease, supporting the hypothesis that 'haploinsufficiency'
      explains development of the ADPKD phenotype. In the present study, we further
      investigated the Pkd1 haploinsufficiency effect by generating Pkd1 knockdown
      transgenic mice with co-cistronic expression of two miRNA hairpins specific to
      Pkd1 transcript and an Emerald GFP reporter driven by a human ubiquitin B
      promoter. Two transgenic lines which had ~60-70% reduction of Pkd1 expression
      developed severe renal cystic disease at a rate similar to that of human ADPKD.
      These results further support the haploinsufficiency hypothesis, and suggest that
      the onset and progression of the renal cystic diseases are correlated with the
      level of Pkd1 expression. The two novel mutant lines of mice appear to be ideal
      models for the study of ADPKD.

PMID- 20814902
TI  - Aberrant expression of LMO4 induces centrosome amplification and mitotic spindle
      abnormalities in breast cancer cells.
AB  - The LIM-only protein, LMO4, is a transcriptional modulator overexpressed in
      breast cancer. It is oncogenic in murine mammary epithelium and is required for
      G2/M progression of ErbB2-dependent cells as well as growth and invasion of other
      breast cancer cell types. However, the mechanisms underlying the oncogenic
      activity of LMO4 remain unclear. Herein, we show that LMO4 is expressed in all
      breast cancer subtypes examined and its expression level correlates with the
      degree of proliferation of such tumours. In addition, we have determined that
      LMO4 silencing induces G2/M arrest in cells from various breast cancer subtypes,
      suggesting that LMO4 action in the cell cycle is not restricted to a single
      breast cancer subtype. This arrest was accompanied by increased cell death,
      amplification of centrosomes, and formation of abnormal mitotic spindles.
      Consistent with its ability to positively and negatively regulate the formation
      of active transcription complexes, overexpression of LMO4 also resulted in an
      increase in centrosome number. Centrosome amplification has been shown to prolong
      the G2/M phase of the cell cycle and induce apoptosis; thus, we conclude that
      supernumerary centrosomes mediate the G2/M arrest and cell death in LMO4
      deficient cells. Furthermore, the correlation of centrosome amplification with
      genomic instability suggests that the impact of dysregulated LMO4 on the
      centrosome cycle may promote LMO4-induced tumour formation.

PMID- 20814904
TI  - Trace detection of the chlorohydrins of epoxidized soybean oil in foodstuffs by
      UPLC-ESI-MS/MS.
AB  - Epoxidized soybean oil (ESBO) is used as an authorized plasticizer and a
      stabilizer for plastic polymers such as poly(vinyl chloride) (PVC). Recently,
      however, there has been a concrete effort devoted to its substitution for other
      plasticizers such as polyadipates. ESBO is exploited particularly in food closure
      gaskets for metal lids used to seal glass jars and bottles. The closure gaskets
      form an airtight seal necessary to prevent microbiological contamination. Thus,
      there are potential uses for food sterilization and storage. Additionally, the
      main pathway of PVC degradation involves the elimination of HCl, which can react
      with the epoxy groups of ESBO to give mono-, polychlorohydrins and/or other
      cyclic derivatives. The European Food Safety Authority noted that not enough
      analytical and toxicological data exist to express a formal opinion on the
      significance for the health effects of such derivatives. At present in the
      scientific literature, there are only a few indicative results of direct
      measurements of ESBO derivatives and there are no official analytical methods
      available for the determination of chlorohydrins directly from foodstuffs. This
      study presents the first example of the analysis of commercial food sauces for
      the detection of ESBO-chlorohydrins (as methyl esters). The results are obtained
      by a dedicated development of an ultraperformance liquid chromatography
      electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) method. Sample
      preparation was based on the following main steps: organic extraction,
      transesterification and solid-phase extraction clean up. In particular, four
      isomers for 18-E-OHCl chlorohydrin and eight isomers for 18-2OHCl chlorohydrin
      were separated and identified. Different food sauces samples closed in glass jars
      with twist-off caps were subjected to qualitative determination, which yielded
      positive results for 18-E-OHCl, whereas no traces of 18-2OHCl were found.

PMID- 20814905
TI  - Simultaneous determination of deoxynivalenol, zearalenone, T-2 and HT-2 toxins in
      breakfast cereals and baby food by high-performance liquid chromatography and
      tandem mass spectrometry.
AB  - In this study, the simultaneous determination of deoxynivalenol (DON),
      zearalenone (ZEA), T-2 and HT-2 toxins in foodstuff was investigated. A new kind
      of multi-mycotoxin immunoaffinity columns (IACs) available on the market (DZT MS
      PREP((r))) was tested. A sensitive, selective and accurate method by high
      performance liquid chromatography and tandem mass spectrometry was developed,
      with electrospray ionization mass spectrometer operating in multiple reaction
      monitoring (MRM) mode, with negative-positive-negative ion switching. The method
      was used for the analysis of samples marked in Italy, in the frame of official
      monitoring plans. The advantages of combining IACs and LC-MS/MS technique are as
      follows: efficient removal of matrix interferences, simple chromatographic
      outline, high selectivity, low detection limits (DLs) and separation of a wide
      range of molecules with different physico-chemical properties in a single run.
      The method was studied on two different matrices, breakfast cereal and baby food,
      at contamination levels close to Regulation limits (EC) 1126/2007. The recoveries
      obtained (60-100%) fulfil the performance criteria required by Regulation (EC)
      401/2006. The DL is 60 ug/kg for DON and 10 ug/kg for ZEA, T-2 and HT-2.
      Linearity range of the calibration curves is suitable for adult and baby food.

PMID- 20814906
TI  - Simultaneous HPLC-DAD-MS (ESI+) determination of structural and geometrical
      isomers of carotenoids in mature grapes.
AB  - Carotenoids are uniquely functional polyene pigments ubiquitous in nature; aside
      from being responsible for the color of a wide variety of vegetables, interest is
      being focused on food carotenoids due to their likely health benefits. From
      analytical point of view, it is important to unequivocally identify individual
      carotenoid compounds in many food stuffs. Therefore, isolation of standards from
      natural sources must be encouraged for accurate identifications. Like many
      fruits, mature grape berries contain numerous carotenoid compounds, mostly found
      in the skin at levels two to three times higher than in the pulp. Carotenoid
      compounds in a typical wine grape variety (Negroamaro) grown in Apulian region
      were investigated by reversed-phase C(30) (RP-30) HPLC-DAD-MS (ESI(+)) analysis.
      As a consequence of an unusual ionization process of carotenoids, their mass
      spectra registered in the positive ion mode comprised both protonated molecules
      and molecular ion radicals with little fragmentation. Additionally, selective
      collision-induced dissociation (CID) experiments, together with fine structures
      of the UV-vis spectra, were used to differentiate structural and geometrical
      isomers. This technique allowed the simultaneous determination of regio- and cis
      isomers of lutein (zeaxanthin, 9Z and 9'Z-lutein) and a cis-isomer of beta
      carotene (9Z- beta-carotene), 5,6-epoxy xanthophylls (violaxanthin, (9'Z)
      neoxanthin, lutein-5,6-epoxide) and 5,8-epoxy xanthophylls diasteroisomers
      (neochrome, auroxanthin, luteoxanthin, flavoxanthin, chrysanthemaxanthin).

PMID- 20814907
TI  - Optimization of oxidative folding methods for cysteine-rich peptides: a study of
      conotoxins containing three disulfide bridges.
AB  - The oxidative folding of small, cysteine-rich peptides to selectively achieve the
      native disulfide bond connectivities is critical for discovery and structure
      function studies of many bioactive peptides. As the propensity to acquire the
      native conformation greatly depends on the peptide sequence, numerous empirical
      oxidation methods are employed. The context-dependent optimization of these
      methods has thus far precluded a generalized oxidative folding protocol, in
      particular for peptides containing more than two disulfides. Herein, we compare
      the efficacy of optimized solution-phase and polymer-supported oxidation methods
      using three disulfide-bridged conotoxins, namely u-SIIIA, u-KIIIA and omega-GVIA.
      The use of diselenide bridges as proxies for disulfide bridges is also evaluated.
      We propose the ClearOx-assisted oxidation of selenopeptides as a fairly
      generalized oxidative folding protocol.

PMID- 20814908
TI  - Native chemical ligation of hydrophobic peptides in organic solvents.
AB  - The application of chemistry to hydrophobic peptides and membrane-spanning
      helices is hampered by the fact that they are only poorly soluble in aqueous
      buffers and that they have a tendency for aggregation. These properties lead to
      difficulties when purifying them after chemical synthesis and particularly
      interfere with native chemical ligation. Here, we describe native chemical
      ligation of model peptides in the organic solvent dimethylformamide (DMF) under
      anhydrous conditions. Best results concerning yields and complete solubility are
      obtained if thiophenole is used in the presence of LiCl. These conditions might
      be applicable also for the ligation of transmembrane helices.

PMID- 20814909
TI  - Segmentation and tracking of cytoskeletal filaments using open active contours.
AB  - We use open active contours to quantify cytoskeletal structures imaged by
      fluorescence microscopy in two and three dimensions. We developed an interactive
      software tool for segmentation, tracking, and visualization of individual fibers.
      Open active contours are parametric curves that deform to minimize the sum of an
      external energy derived from the image and an internal bending and stretching
      energy. The external energy generates (i) forces that attract the contour toward
      the central bright line of a filament in the image, and (ii) forces that stretch
      the active contour toward the ends of bright ridges. Images of simulated
      semiflexible polymers with known bending and torsional rigidity are analyzed to
      validate the method. We apply our methods to quantify the conformations and
      dynamics of actin in two examples: actin filaments imaged by TIRF microscopy in
      vitro, and actin cables in fission yeast imaged by spinning disk confocal
      microscopy.

PMID- 20814911
TI  - Ontogenetic changes in the epiphyseal cartilage of Rana (Pelophylax) caralitana
      (Anura: Ranidae).
AB  - We document histological changes through ontogeny in the epiphyseal cartilage of
      the third phalanx of Rana caralitana from Turkey and provide an assessment of the
      maturation of the epiphysis from newly metamorphosed froglets to 10-year-old
      individuals. The epiphysis of R. caralitana is compared to other Rana taxa
      previously studied, and we report on novel histological data pertaining to later
      stages of epiphyseal growth in this taxon. In addition, we document the
      development of endochondral ossification in late stages of ontogeny in R.
      caralitana. Our results suggest a correlation between the long lifespan of R.
      caralitana and the developmental changes and maturation of the epiphyseal
      cartilage in this taxon. This study also provides a quantitative assessment of
      the different regions of the epiphyseal cartilage in the epiphysis of Rana
      through ontogeny, and has therefore permitted quantifiable deductions about the
      relative maturation and differentiation of the chondrocytes of the epiphysis
      through time.

PMID- 20814910
TI  - Coupling between microtubule sliding, plus-end growth and spindle length revealed
      by kinesin-8 depletion.
AB  - Mitotic spindle length control requires coordination between microtubule (MT)
      dynamics and motor-generated forces. To investigate how MT plus-end
      polymerization contributes to spindle length in Drosophila embryos, we studied
      the dynamics of the MT plus-end depolymerase, kinesin-8, and the effects of
      kinesin-8 inhibition using mutants and antibody microinjection. As expected,
      kinesin-8 was found to contribute to anaphase A. Furthermore, kinesin-8 depletion
      caused: (i) excessive polymerization of interpolar (ip) MT plus ends, which
      "overgrow" to penetrate distal half spindles; (ii) an increase in the poleward
      ipMT sliding rate that is coupled to MT plus-end polymerization; (iii) premature
      spindle elongation during metaphase/anaphase A; and (iv) an increase in the
      anaphase B spindle elongation rate which correlates linearly with the MT sliding
      rate. This is best explained by a revised "ipMT sliding/minus-end
      depolymerization" model for spindle length control which incorporates a coupling
      between ipMT plus end dynamics and the outward ipMT sliding that drives poleward
      flux and spindle elongation.

PMID- 20814912
TI  - The role of medical museums in contemporary medical education.
AB  - From the early 19th century until the most recent two decades, open-space and
      satellite museums featuring anatomy and pathology collections (collectively
      referred to as "medical museums") had leading roles in medical education.
      However, many factors have caused these roles to diminish dramatically in recent
      years. Chief among these are the great advances in information technology and web
      based learning that are currently at play in every level of medical training.
      Some medical schools have abandoned their museums while others have gradually
      given away their museums' contents to devote former museum space to new
      classrooms, lecture halls, and laboratories. These trends have accelerated as
      medical school enrollment has increased and as increasing interest in biological
      and biomedical research activities have caused medical schools to convert museum
      space into research facilities. A few medical schools, however, have considered
      the contents of their museums as irreplaceable resources for modern medicine and
      medical education and the space these occupy as great environments for
      independent and self-directed learning. Consequently, some medical schools have
      updated their medical museums and equipped them with new technologies. The
      Anatomical Museum of Leiden University Medical Center in The Netherlands and the
      Medical Museum of Kawasaki Medical School in Kurashiki, Okayama, Japan, are two
      examples of such upgraded museums. Student surveys at Leiden University have
      indicated that all students (100%) found audio-guided museum tours to be useful
      for learning and majorities of them found guided tours to be clinically relevant
      (87%). However, 69% of students felt that museum visits should be optional rather
      than compulsory within the medical training curriculum.

PMID- 20814913
TI  - Student-centered integrated anatomy resource sessions at Alfaisal University.
AB  - Alfaisal University is a new medical school in Riyadh, Kingdom of Saudi Arabia
      that matriculates eligible students directly from high school and requires them
      to participate in a hybrid problem-based learning (PBL) curriculum. PBL is a well
      established student-centered approach, and the authors have sought to examine if
      a student-centered, integrated approach to learn human structures leads to
      positive perceptions of learning outcomes. Ten students were divided into four
      groups to rotate through wet and dry laboratory stations (integrated resource
      sessions, IRSs) that engaged them in imaging techniques, embryology, histology,
      gross anatomy (dissections and prosections), surface anatomy, and self-directed
      learning questions. All IRSs were primarily directed by students. During two
      second-semester organ system blocks, forty students responded to a structured
      questionnaire designed to poll students' perceptions of changes in their
      knowledge, skills, and attitudes as a result of IRS. The majority (60%) of
      students felt that the student-centered approach to learning enhanced their
      medical knowledge. Most students also felt that the IRS approach was advantageous
      for formulating clear learning objectives (55%) and in preparing for examinations
      (65%). Despite their positive feelings toward IRS, students did not view this
      learning approach as an adequate replacement for the knowledge gained from
      lectures and textbooks. Students' performance on objective structured practical
      examinations improved significantly for the two curricular blocks that included
      IRS compared with earlier non-IRS blocks. A student-centered approach to teach
      human structure in a hybrid PBL curriculum may enhance understanding of the basic
      sciences in first-year medical students.

PMID- 20814914
TI  - The use of self-learning modules to facilitate learning of basic science concepts
      in an integrated medical curriculum.
AB  - This study used qualitative and quantitative approaches to evaluate the
      effectiveness of self-learning modules (SLMs) developed to facilitate and
      individualize students' learning of basic medical sciences. Twenty physiology and
      nineteen microanatomy SLMs were designed with interactive images, animations,
      narrations, and self-assessments. Of 41 medical students, 40 students voluntarily
      completed a questionnaire with open-ended and closed-ended items to evaluate
      students' attitudes and perspectives on the learning value of SLMs. Closed-ended
      items were assessed on a five-point Likert scale (5 = high score) and the data
      were expressed as mean +/- standard deviation. Open-ended questions further
      evaluated students' perspectives on the effectiveness of SLMs; student responses
      to open-ended questions were analyzed to identify shared patterns or themes in
      their experience using SLMs. The results of the midterm examination were also
      analyzed to compare student performance on items related to SLMs and traditional
      sessions. Students positively evaluated their experience using the SLMs with an
      overall mean score of 4.25 (SD +/- 0.84). Most students (97%) indicated that the
      SLMs improved understanding and facilitated learning basic science concepts. SLMs
      were reported to allow learner control, to help in preparation for subsequent in
      class discussion, and to improve understanding and retention. A significant
      difference in students' performance was observed when comparing SLM-related items
      with non-SLM items in the midterm examination (P < 0.05). In conclusion, the use
      of SLMs in an integrated basic science curriculum has the potential to
      individualize the teaching and improve the learning of basic sciences.

PMID- 20814915
TI  - Demonstration of pelvic anatomy by modified midline transection that maintains
      intact internal pelvic organs.
AB  - Gross dissection for demonstrating anatomy of the human pelvis has traditionally
      involved one of two approaches, each with advantages and disadvantages. Classic
      hemisection in the median plane through the pelvic ring transects the visceral
      organs but maintains two symmetric pelvic halves. An alternative paramedial
      transection compromises one side of the bony pelvis but leaves the internal
      organs intact. The authors propose a modified technique that combines advantages
      of both classical dissections. This novel approach involves dividing the pubic
      symphysis and sacrum in the median plane after shifting all internal organs to
      one side. The hemipelvis without internal organs is immediately available for
      further dissection of the lower limb. The hemipelvis with intact internal organs
      is ideal for showing the complex spatial relationships of the pelvic organs and
      vessels relative to the intact pelvic floor.

PMID- 20814916
TI  - Design considerations for plasmonic photovoltaics.
AB  - This paper reviews the recent research progress in the incorporation of plasmonic
      nanostructures with photovoltaic devices and the potential for surface plasmon
      enhanced absorption. We first outline a variety of cell architectures
      incorporating metal nanostructures. We then review the experimental fabrication
      methods and measurements to date, as well as systematic theoretical studies of
      the optimal nanostructure shapes. Finally we discuss photovoltaic absorber
      materials that could benefit from surface plasmon enhanced absorption.

PMID- 20814917
TI  - Enhancement in light emission efficiency of a silicon nanocrystal light-emitting
      diode by multiple-luminescent structures.

PMID- 20814918
TI  - Surface wrinkling: a versatile platform for measuring thin-film properties.
AB  - Surface instabilities in soft matter have been the subject of increasingly
      innovative research aimed at better understanding the physics of their formation
      and their utility in patterning, organizing, and measuring materials properties
      on the micro and nanoscale. The focus of this Review is on a type of instability
      pattern known as surface wrinkling, covering the general concepts of this
      phenomenon and several recent applications involving the measurement of thin-film
      properties. The ability of surface wrinkling to yield new insights into
      particularly challenging materials systems such as ultrathin films, polymer
      brushes, polyelectrolyte multilayer assemblies, ultrasoft materials, and
      nanoscale structured materials is highlighted. A perspective on the future
      directions of this maturing field, including the prospects for advanced thin-film
      metrology methods, facile surface patterning, and the control of topology
      sensitive phenomena, such as wetting and adhesion, is also presented.

PMID- 20814919
TI  - Diverse 3D microarchitectures made by capillary forming of carbon nanotubes.
AB  - A new technology called capillary forming enables transformation of vertically
      aligned nanoscale filaments into complex three-dimensional microarchitectures. We
      demonstrate capillary forming of carbon nanotubes into diverse forms having
      intricate bends, twists, and multidirectional textures. In addition to their
      novel geometries, these structures have mechanical stiffness exceeding that of
      microfabrication polymers, and can be used as masters for replica molding

PMID- 20814920
TI  - Novel MOF-membrane for molecular sieving predicted by IR-diffusion studies and
      molecular modeling.

PMID- 20814921
TI  - Nanosensors: does crystal shape matter?

PMID- 20814922
TI  - Anatase mesoporous TiO2 nanofibers with high surface area for solid-state dye
      sensitized solar cells.
AB  - Mesoporous nanofibers (NFs) with a high surface area of 112 m(2)/g have been
      prepared by electrospinning technique. The structures of mesoporous NFs and
      regular NFs are characterized and compared through scanning electron microscope
      (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and
      selected area electron diffraction (SAED) studies. Using mesoporous TiO(2) NFs as
      the photoelectrode, solid-state dye-sensitized solar cells (SDSCs) have been
      fabricated employing D131 as the sensitizer and P3HT as the hole transporting
      material to yield an energy conversion efficiency (eta) of 1.82%. A J(sc) of
      3.979 mA cm(-2) is obtained for mesoporous NF-based devices, which is 3-fold
      higher than that (0.973 mA cm(-2)) for regular NF-based devices fabricated under
      the same condition (eta = 0.42%). Incident photon-to-current conversion
      efficiency (IPCE) and dye-desorption test demonstrate that the increase in J(sc)
      is mainly due to greatly improved dye adsorption for mesoporous NFs as compared
      to that for regular NFs. In addition, intensity modulated photocurrent
      spectroscopy (IMPS) and intensity modulated photovoltage spectroscopy (IMVS)
      measurements indicate that the mesopores on NF surface have very minor effects on
      charge transport and collection. Initial aging test proves good stability of the
      fabricated devices, which indicates the promise of mesoporous NFs as
      photoelectrode for low-cost SDSCs.

PMID- 20814924
TI  - Fusion and fission control of picoliter-sized microdroplets for changing the
      solution concentration of microreactors.

PMID- 20814923
TI  - Magnetic luminescent porous silicon microparticles for localized delivery of
      molecular drug payloads.
AB  - Magnetic manipulation, fluorescent tracking, and localized delivery of a drug
      payload to cancer cells in vitro is demonstrated, using nanostructured porous
      silicon microparticles as a carrier. The multifunctional microparticles are
      prepared by electrochemical porosification of a silicon wafer in a hydrofluoric
      acid-containing electrolyte, followed by removal and fracture of the porous layer
      into particles using ultrasound. The intrinsically luminescent particles are
      loaded with superparamagnetic iron oxide nanoparticles and the anti-cancer drug
      doxorubicin. The drug-containing particles are delivered to human cervical cancer
      (HeLa) cells in vitro, under the guidance of a magnetic field. The high
      concentration of particles in the proximity of the magnetic field results in a
      high concentration of drug being released in that region of the Petri dish, and
      localized cell death is confirmed by cellular viability assay (Calcein AM).

PMID- 20814925
TI  - Quantum-dot-encoded silica nanospheres for nucleic acid hybridization.

PMID- 20814926
TI  - Porous graphene as an atmospheric nanofilter.
AB  - The fabrication of nanoscale membranes exhibiting high selectivity is an emerging
      field of research. The possibility to use bottom-up approaches to fabricate a
      filter with porous graphene and analyze its functionality with first principle
      calculations is investigated. Here, the porous network is produced by self
      assembly of the hexaiodo-substituted macrocycle cyclohexa-m-phenylene (CHP). The
      resulting porous network exhibits an extremely high selectivity in favor of H(2)
      and He among other atmospheric gases, such as Ne, O(2), N(2), CO, CO(2), NH(3),
      and Ar. The presented membrane is superior to traditional filters using polymers
      or silica and could have great potential for further technological applications
      such as gas sensors or fuel cells.

PMID- 20814927
TI  - Spatially controlled amyloid reactions using organic electronics.
AB  - Abnormal protein aggregates, so called amyloid fibrils, are mainly known as
      pathological hallmarks of a wide range of diseases, but in addition these robust
      well-ordered self-assembled natural nanostructures can also be utilized for
      creating distinct nanomaterials for bioelectronic devices. However, current
      methods for producing amyloid fibrils in vitro offer no spatial control. Herein,
      we demonstrate a new way to produce and spatially control the assembly of amyloid
      like structures using an organic electronic ion pump (OEIP) to pump distinct
      cations to a reservoir containing a negatively charged polypeptide. The
      morphology and kinetics of the created proteinaceous nanomaterials depends on the
      ion and current used, which we leveraged to create layers incorporating different
      conjugated thiophene derivatives, one fluorescent (p-FTAA) and one conducting
      (PEDOT-S). We anticipate that this new application for the OEIP will be useful
      for both biological studies of amyloid assembly and fibrillogenesis as well as
      for creating new bioelectronic nanomaterials and devices.

PMID- 20814928
TI  - Cardiac function in trisomy 21 fetuses.
AB  - OBJECTIVES: Trisomy 21 is associated with an increased nuchal translucency
      thickness (NT), abnormal ductus venosus (DV) flow at 11-14 weeks' gestation and
      congenital heart defects (CHD), and cardiac dysfunction has been hypothesized as
      the link between them. We therefore aimed to investigate whether cardiac function
      is altered in trisomy 21 fetuses. METHODS: Between December 2003 and June 2009,
      we performed echocardiography on 46 trisomy 21 fetuses (28 with structurally
      normal heart and 18 with CHD) and on 191 chromosomally/phenotypically normal
      fetuses with a confirmed normal heart (87 with normal NT and 104 with NT >=
      95(th) percentile), between 11 and 35 weeks' gestation. Measurements included: E-
      and A-wave peak velocity, E/A velocity ratio and E/time velocity integral (TVI)
      ratio over atrioventricular valves; myocardial performance index (MPI); semilunar
      valve peak velocity and acceleration time; stroke volume (SV); cardiac output;
      and DV pulsatility index for veins (PIV) at 11-14 weeks' gestation. Data were
      categorized into three different age groups for analysis (11 to 13 + 6, 14 to 21
      + 6 and 22 to 35 weeks' gestation). RESULTS: The tricuspid valve (TV) A-wave
      velocity and aortic valve peak velocity were significantly reduced in trisomy 21
      compared with normal fetuses. Other highly significant differences found in
      trisomy 21 fetuses at 11-14 weeks' were increased TV-E/A ratio and DV-PIV, and
      decreased pulmonary valve peak velocity. We also observed evidence of left
      ventricular (LV) systolic dysfunction, reduced SV and increased MPI. After 14
      weeks' gestation, the mitral valve A-wave peak velocity and E/TVI ratio were
      significantly reduced in the trisomy 21 fetuses with normal hearts compared with
      the controls with increased NT. CONCLUSIONS: In comparison with controls with
      normal or increased NT, cardiac function in trisomy 21 fetuses is abnormal
      irrespective of the presence of CHD. Evidence for cardiac loading (increased
      preload and afterload) and LV systolic (in the first trimester) and later
      diastolic dysfunction was observed.

PMID- 20814929
TI  - Application of dynamic light scattering in protein crystallization.
AB  - Success in determining the three-dimensional structure of a macromolecule by X
      ray diffraction methods depends critically on the ability to obtain well ordered
      crystals of the macromolecule in question. Predisposition to crystallization
      correlates with the homogeneity of the molecules in solution. Dynamic light
      scattering (DLS) is particularly well suited for evaluating protein homogeneity
      under multiple conditions and at concentrations commensurate with crystallization
      conditions. This unit presents a typical protocol for DLS measurements of a
      protein sample, and describes approaches to improve protein homogeneity in
      solution.

PMID- 20814930
TI  - The STINT-NMR method for studying in-cell protein-protein interactions.
AB  - This unit describes critical components and considerations required to study
      protein-protein structural interactions inside a living cell by using NMR
      spectroscopy (STINT-NMR). STINT-NMR entails sequentially expressing two (or more)
      proteins within a single bacterial cell in a time-controlled manner and
      monitoring their interactions using in-cell NMR spectroscopy. The resulting
      spectra provide a complete titration of the interaction and define structural
      details of the interacting surfaces at the level of single amino acid residues.
      The advantages and limitations of STINT-NMR are discussed, along with the
      differences between studying macromolecular interactions in vitro and in vivo (in
      cell). Also described are considerations in the design of STINT-NMR experiments,
      focusing on selecting appropriate overexpression plasmid vectors, sample
      requirements and instrumentation, and the analysis of STINT-NMR data, with
      specific examples drawn from published works. Applications of STINT-NMR,
      including an in-cell methodology to post-translationally modify interactor
      proteins and an in-cell NMR assay for screening small molecule interactor
      libraries (SMILI-NMR) are presented.

PMID- 20814931
TI  - Combinatorial recombination of gene fragments to construct a library of chimeras.
AB  - Recombination of distantly related and nonrelated genes is difficult using
      traditional PCR-based techniques, and truncation-based methods result in a large
      proportion of nonviable sequences due to frame shifts, deletions, and insertions.
      This unit describes a method for creating libraries of chimeras through
      combinatorial assembly of gene fragments. It allows the experimenter to recombine
      genes of any identity and to select the sites where recombination takes place.
      Combinatorial recombination is achieved by generating gene fragments with
      specific overhangs, or sticky ends. The overhangs permit the fragments to be
      ligated in the correct order while allowing independent assortment of blocks with
      identical overhangs. Genes of any identity can be recombined so long as they
      share 3 to 5 base pairs of identity at the desired recombination sites. Simple
      adaptations of the method allow incorporation of specific gene fragments.

PMID- 20814932
TI  - Strategies to optimize protein expression in E. coli.
AB  - Recombinant protein expression in Escherichia coli (E. coli) is simple, fast,
      inexpensive, and robust, with the expressed protein comprising up to 50 percent
      of the total cellular protein. However, it also has disadvantages. For example,
      the rapidity of bacterial protein expression often results in unfolded/misfolded
      proteins, especially for heterologous proteins that require longer times and/or
      molecular chaperones to fold correctly. In addition, the highly reductive
      environment of the bacterial cytosol and the inability of E. coli to perform
      several eukaryotic post-translational modifications results in the insoluble
      expression of proteins that require these modifications for folding and activity.
      Fortunately, multiple, novel reagents and techniques have been developed that
      allow for the efficient, soluble production of a diverse range of heterologous
      proteins in E. coli. This overview describes variables at each stage of a protein
      expression experiment that can influence solubility and offers a summary of
      strategies used to optimize soluble expression in E. coli.

PMID- 20814933
TI  - Elastin-like polypeptides as a purification tag for recombinant proteins.
AB  - This unit presents a recombinant protein purification method that employs an
      elastin-like polypeptide (ELP) as a purification tag. ELPs undergo a sharp and
      reversible phase transition when heated above their lower critical solution
      temperature. ELPs retain this behavior when they are fused to a protein, and
      thereby provide a simple method to isolate a recombinant ELP fusion protein from
      cell contaminants by cycling the solution through the insoluble and soluble phase
      of the ELP fusion protein using a procedure that is termed Inverse Transition
      Cycling. This method does not require the use of chromatography, so it is cost
      effective, easy to scale up, and easy to multiplex.

PMID- 20814934
TI  - Reversed-phase High Performance Liquid Chromatography of proteins.
AB  - Reversed-phase HPLC (RP-HPLC) is one of most important techniques for protein
      separations and the method of choice for peptide separation. RP-HPLC has been
      applied on the nano, micro, and analytical scale, and has also been scaled up for
      preparative purifications, to large industrial scale. Because of its
      compatibility with mass spectrometry, RP-HPLC is an indispensable tool in
      proteomic research. With modern instrumentation and columns, complex mixtures of
      peptides and proteins can be separated at attomolar levels for further analysis.
      In addition, preparative RP-HPLC is often used for large-scale purification of
      proteins. This unit provides protocols for packing and testing a column, protein
      separation by use of gradient or step elution, desalting of protein solutions,
      and separation of enzymatic digests before mass spectrometric analyses. A
      protocol is also provided for cleaning, regenerating, and storing reversed-phase
      chromatography columns.

PMID- 20814935
TI  - Clump passaging and expansion of human embryonic and induced pluripotent stem
      cells on mouse embryonic fibroblast feeder cells.
AB  - The ability of human embryonic stem cells (hESCs) to differentiate into
      essentially all somatic cell types has made them a valuable tool for studying
      human development and has positioned them for broad applications in toxicology,
      regenerative medicine, and drug discovery. This unit describes a protocol for the
      large-scale expansion and maintenance of hESCs in vitro. hESC cultures must
      maintain a balance between the cellular states of pluripotency and
      differentiation; thus, researchers must use care when growing these technically
      demanding cells. The culture system is based largely on the use of a proprietary
      serum-replacement product and basic fibroblast growth factor (bFGF), with mouse
      embryonic fibroblasts as a feeder layer. These conditions provide the basis for
      relatively inexpensive maintenance and expansion of hESCs, as well as their
      engineered counterparts, human induced pluripotent stem cells (hiPSCs).

PMID- 20814936
TI  - Expansion of human embryonic stem cells on cellulose microcarriers.
AB  - This unit describes the routine maintenance and expansion of undifferentiated
      human embryonic stem cells (hESC) on cellulose microcarriers. Conventionally,
      hESCs have been maintained on feeder cells or extracellular matrix-coated two
      dimensional tissue culture plates. The expansion of hESC on a tissue culture
      platform is limited by the available surface area and the requirement of
      repetitive subculturing to reach the required cell yield. Here, we show that
      expansion of hESC can be carried out in a three-dimensional suspension culture
      using Matrigel-coated cellulose microcarriers. hESCs from a tissue culture plate
      can be seeded directly onto the microcarriers; hESC microcarrier culture is
      passaged and expanded by mechanical dissociation of the cells without enzyme.
      Expansion of the culture in a 100-ml spinner flask is also described. Long-term
      culture of hESC on the microcarriers maintains typical pluripotent markers (OCT
      4, Tra-1-60, and SSEA-4) and stable karyotype. Spontaneous differentiations of
      microcarrier-maintained hESCs in vitro (embryoid body formation) and in vivo
      (teratoma formation in SCID mouse) have demonstrated formation of the three germ
      layers. These protocols can also be applied equally well to human induced
      pluripotent stem cells.

PMID- 20814937
TI  - Isolation and functional characterization of pluripotent stem cell-derived
      cardiac progenitor cells.
AB  - The use of transgenic markers in pluripotent stem cells allows the facile
      isolation of transient cell populations that appear at certain phases of
      embryonic development. Here, we describe a procedure for deriving cardiac
      progenitors from mouse pluripotent stem cells carrying a GFP reporter under the
      control of an Nkx2.5 enhancer sequence. The cells are propagated under standard
      conditions and are differentiated using the hanging-droplet method with medium
      optimized for commitment to the cardiac lineage. Cardiac progenitors are isolated
      from the differentiation culture using fluorescence-activated cell sorting (FACS)
      and can be cultured further for functional characterization and experimentation.
      The protocols described here can be applied to both embryonic and induced
      pluripotent stem cells and can easily be adapted to transgenic lines carrying
      other cardiac cell lineage reporters.

PMID- 20814938
TI  - Preparation of hematopoietic stem and progenitor cells from the human placenta.
AB  - This unit describes a protocol to isolate hematopoietic progenitors and stem
      cells from human placentae isolated at different time points in development and
      at the full-term gestational stage. The placenta is extensively washed to
      eliminate blood contamination on its surface and inside the villi (the vascular
      compartments of the placenta). The placenta is then mechanically minced into
      pieces, which are subsequently digested with an enzyme cocktail. After
      dissociation and filtration, placental cells are available for further phenotypic
      and functional analyses.

PMID- 20814939
TI  - Signal transduction during activation and inhibition of natural killer cells.
AB  - Natural killer (NK) cells are important for early immune responses to viral
      infections and cancer. Upon activation, NK cells secrete cytokines and
      chemokines, and kill sensitive target cells by releasing the content of cytolytic
      granules. This unit is focused on the signal transduction pathways that regulate
      NK cell activities in response to contact with other cells. We will highlight
      signals regulating NK cell adhesion to target cells and describe the induction of
      cellular cytotoxicity by the engagement of different NK cell activation
      receptors. Negative signaling induced by inhibitory receptors opposes NK cell
      activation and provides an important safeguard from NK cell reactivity toward
      normal, healthy cells. We will discuss the complex integration of the different
      signals that occur during interaction of NK cells with target cells.

PMID- 20814940
TI  - Isolation and functional use of human NKT cells.
AB  - This unit details methods for the isolation, in vitro expansion, and functional
      characterization of human iNKT cells. The term iNKT derives from the fact that a
      large fraction of murine NKT cells recognize the MHC class I-like CD1d protein,
      are CD4+ or CD4-CD8- (double negative), and use an identical "invariant" TCRalpha
      chain, which is generated by precise Valpha14 and Jalpha281 (now renamed
      Jalpha18) rearrangements with either no N-region diversity or subsequent trimming
      to nearly identical amino-acid sequence (hence, 'iNKT'). Basic Protocol 1 and
      Alternate Protocol 1 use multi-color FACS analysis to identify and quantitate
      rare iNKT cells from human samples. Basic Protocol 2 describes iNKT cell
      purification. Alternate Protocol 2 describes a method for high-speed FACS sorting
      of iNKT cells. Alternate Protocol 3 employs a cell sorting approach to isolate
      iNKT cell clones. A Support Protocol for secondary stimulation and rapid
      expansion of iNKT cells is also included. Basic Protocol 3 explains functional
      analysis of iNKT.

PMID- 20814941
TI  - Isolation of tissue mast cells.
AB  - Located primarily in tissues, mast cells are one of the principal effector cells
      in allergic inflammation. Mast cells derive from mononuclear precursor cells
      which undergo their final phase of differentiation in the tissues. Mast cells
      express a unique set of proteases and display functional diversity depending on
      the tissue in which they differentiate--a phenomenon often referred to as mast
      cell heterogeneity. Enzymatic digestion and density centrifugation have often
      been used to isolate human mast cells from tissues such as lung and skin,
      frequently resulting in cells with low viability and purity. Here, we describe a
      protocol that combines gentle enzymatic digestion with positive selection
      techniques to isolate reasonably viable and substantially enriched preparations
      of tissue mast cells.

PMID- 20814942
TI  - Generation, isolation, and maintenance of human mast cells and mast cell lines
      derived from peripheral blood or cord blood.
AB  - Antigen-mediated mast cell activation is a pivotal step in the initiation of
      allergic disorders including anaphylaxis and atopy. To date, studies aimed at
      investigating the mechanisms regulating these responses, and studies designed to
      identify potential ways to prevent them, have primarily been conducted in rodent
      mast cells. However, to understand how these responses pertain to human disease,
      and to investigate and develop novel therapies for the treatment of human mast
      cell-driven disease, human mast cell models may have greater relevance. Recently,
      a number of systems have been developed to allow investigators to readily obtain
      sufficient quantities of human mast cells to conduct these studies. These mast
      cells release the appropriate suite of inflammatory mediators in response to
      known mast cell activators including antigen. These systems have also been
      employed to examine the signaling events regulating these responses. Proof of
      principle studies has also demonstrated utility of these systems for the
      identification of potential inhibitors of mast cell activation and growth. In
      this unit, techniques for the development and culture of human mast cells from
      their progenitors and the culture of human mast cell lines are described. The
      relative merits and drawbacks of each model are also described.

PMID- 20814943
TI  - Epitope mapping using gram-positive surface display.
AB  - Antibodies have proven to be invaluable tools for a vast number of applications
      during the last decades, including protein purification and characterization,
      medical diagnosis and imaging, and treatment using therapeutic antibiotics. No
      matter what the aims of the application are, the antibody's binding
      characteristics will still be the main features determining the assay's
      reliability. Here, we describe a protocol for determination of antibody-binding
      epitopes using an antigen-focused, library-based approach where library members
      are generated by fragmentation of antigen DNA and presented as cloned peptides on
      the cell surface of the Gram-positive bacterium Staphylococcus carnosus. The
      rigid cell structure of this organism allows for multivalent expression and
      permits rapid library analysis and sorting of antibody-binding cells using flow
      sorting devices. Epitopes are determined by DNA sequencing of the sorted cells
      and alignment back to the antigen sequence. The protocol described here has been
      shown useful for mapping of both monoclonal and polyclonal binders with varying
      epitope lengths.

PMID- 20814944
TI  - Synthesis of new nonclassical acridines, quinolines, and quinazolines derived
      from dimedone for biological evaluation.
AB  - New nonclassical acridines, quinolines, and quinazolines were prepared starting
      from cyclic beta-diketones, namely dimedone, through application of Hantzsch
      addition, Michael addition, and Mannich reactions, respectively. The
      antimicrobial activity revealed that decahydroacridin-1,8-dione 2e bearing a 3
      nitrophenyl group and hexahydroquinoline 4e having a 2,4-dichlorophenyl moiety
      were the most active compounds against both Gram-positive and -negative bacteria
      based upon using the disc diffusion method. Cytotoxic activity studies for
      decahydroacridin-1,8-diones 2a-e against liver carcinoma cells (HepG(2)) using
      the MTT cell viability assay revealed that decahydroacridin-1,8-dione bearing a 4
      methylphenyl moiety 2d showed a higher cytotoxic activity (IC(50) = 4.42 ug/mL)
      than the other derivatives.

PMID- 20814945
TI  - Marie Unna hereditary hypotrichosis: a Turkish family with loss of eyebrows and a
      U2HR mutation.
AB  - We report a family with Marie Unna hereditary hypotrichosis (MUHH) from Turkey.
      MUHH is a distinct form of scalp and body hair loss characterized by the absence
      or scarcity of scalp hair, eyebrows, and eyelashes at birth. Coarse wiry hair
      begins to grow during childhood. Around puberty, progressive hair loss occurs in
      the affected patients. Recently, mutations were identified in U2HR, an inhibitory
      upstream open reading frame in the 5'-untranslated region of the human hairless
      gene (HR) as the underlying cause of MUHH. We are presenting hair loss of
      eyebrows in a Turkish family comprising eight affected and seven unaffected
      individuals. The pedigree is compatible with autosomal dominant inheritance.
      Linkage and haplotype analyses confirmed linkage of this family to the MUHH locus
      at cytoband 8p21. By sequencing U2HR, we identified the mutation c.2T>C (M1T) in
      all affected family members. We concluded that there may be considerable clinical
      variations in MUHH, and that eyebrow loss is an important clue for accurate
      diagnosis.

PMID- 20814946
TI  - Tissue-limited mosaicism for monosomy 13.
AB  - Karyotypic discordance between different tissues in an individual is uncommon. We
      report on a patient with multiple congenital anomalies and mosaicism for monosomy
      13 limited to fibroblasts. Findings include microcephaly, agenesis of the corpus
      callosum, bilateral posterior colobomas, cataract and optic nerve dysplasia,
      patent foramen ovale, renal hypoplasia, hypospadias and unilateral inguinal
      hernia, unilateral hypoplasia of the lower limb, sparse and patchy hair, subtle
      pigmentary mosaicism, and global developmental delay. The lymphocyte karyotype
      was normal, whereas the fibroblast karyotype showed mosaicism for a del(13)(q11
      >ter). Review of the literature identified three previous reports of similar
      patients with multiple congenital anomalies, normal lymphocyte karyotype, and
      subsequent, diagnostic fibroblast karyotyping. Comparison of the previously
      reported patients with the patient reported here defines a common phenotype for
      tissue-limited mosaicism for monosomy 13 consisting of prenatal-onset growth
      deficiency; microcephaly; facial abnormalities including prominent nasal bridge,
      hypertelorism, ptosis, epicanthal folds, microphthalmia, coloboma,
      retinoblastoma, prominent maxilla, micrognathia, and low-set ears; limb
      abnormalities including small to absent thumbs, clinodactyly of fifth finger,
      fused metacarpal bones 4 and 5, talipes equinovarus, and short first toe; cardiac
      defect; renal anomalies; and genitalia abnormalities including hypospadias and
      cryptorchidism. In conclusion, this case further emphasizes that fibroblast
      karyotyping should be employed when the diagnosis remains unclear, especially in
      the presence of pigmentary mosaicism or segmental hypoplasia.

PMID- 20814947
TI  - Adermatoglyphia, previously unrecognized manifestation in ADULT syndrome.

PMID- 20814948
TI  - Characterization of a complex cryptic mosaicism for an sSMC derived from the X
      chromosome present in a boy with congenital malformations.

PMID- 20814949
TI  - Folic acid flour fortification: impact on the frequencies of 52 congenital
      anomaly types in three South American countries.
AB  - The aim of the present investigation was to search for a reduction in birth
      prevalence estimates of 52 selected types of congenital anomalies, associated
      with folic acid fortification programs in Chile, Argentina, and Brazil. The
      material included 3,347,559 total births in 77 hospitals of the three countries
      during the 1982-2007 period: 596,704 births (17 hospitals) in Chile, 1,643,341
      (41 hospitals) in Argentina, and 1,107,514 (19 hospitals) in Brazil. We compared
      pre- and post-fortification rates within each hospital and the resulting
      Prevalence Rate Ratios (PRRs) were pooled by country. Statistically significant
      reductions in birth prevalence estimates after fortification were observed for
      neural tube defects (NTDs), septal heart defects, transverse limb deficiencies,
      and subluxation of the hip. However, only the reduction of NTDs appeared to be
      associated with folic acid fortification and not due to other factors, because of
      its consistency among the three countries, as well as with previously published
      reports, and its strong statistical significance. Among the NTDs, the maximum
      prevalence reduction was observed for isolated cephalic (cervical-thoracic) spina
      bifida, followed by caudal (lumbo-sacral) spina bifida, anencephaly, and
      cephalocele. This observation suggests etiologic and pathogenetic heterogeneity
      among different levels of spina bifida, as well as among different NTD subtypes.
      We concluded that food fortification with folic acid prevents NTDs but not other
      types of congenital anomalies.

PMID- 20814950
TI  - Early onset mandibuloacral dysplasia due to compound heterozygous mutations in
      ZMPSTE24.
AB  - Mandibuloacral dysplasia (MAD) is an autosomal recessive disorder characterized
      by hypoplasia of the mandible and clavicles, acro-osteolysis, and lipodystrophy
      due to mutations in LMNA or ZMPSTE24. Only six MAD patients are reported so far
      with ZMPSTE24 mutations and limited phenotypic data are available for them. Here,
      we report on two brothers (4 years and 9-month old) with early onset MAD due to
      ZMPSTE24 mutations in whom thin skin was noted as early as 5 months of age. Both
      had micrognathia, mottled hyperpigmentation, and enlarged fontanelles but little
      evidence of lipodystrophy. There was no delay of mental development. The older
      brother had small pinched nose, short clavicles, acro-osteolysis, stunted growth,
      joint stiffness, and repeated fractures. There was no evidence of renal disease.
      Both patients were compound heterozygotes harboring a previously reported
      missense ZMPSTE24 mutation, p.Pro248Leu, and a novel null mutation, p.Trp450stop.
      These patients and the review of literature reveal that compared to MAD patients
      with LMNA mutations, those with ZMPSTE24 mutations develop manifestations earlier
      in life. Other distinguishing features in MAD due to ZMPSTE24 mutations may
      include premature birth, renal disease, calcified skin nodules, and lack of
      acanthosis nigricans. We conclude that in patients with MAD due to ZMPSTE24
      mutations, the onset of disease manifestations such as thin skin and micrognathia
      occurs as early as 5 months of age. In these patients, skeletal phenotype
      presents earlier whereas lipodystrophy and renal disease may occur later in life.

PMID- 20814951
TI  - Craniosynostosis in pycnodysostosis: broadening the spectrum of the cranial flat
      bone abnormalities.
AB  - Pycnodysostosis is a rare autosomal recessive skeletal dysplasia caused by the
      absence of active cathepsin K, which is a lysosomal cysteine protease that plays
      a role in degrading the organic matrix of bones, acting in bone resorption and
      bone remodeling. The disease is primarily characterized by osteosclerosis, bone
      fragility, short stature, acro-osteolysis, and delayed closure of the cranial
      sutures. A differing feature, cranial synostosis, has occasionally been described
      in this disorder. We reviewed six unrelated patients with pycnodysostosis (mean
      age of 10 years and 4 months) in order to evaluate the presence of
      craniosynostosis. In addition to the typical findings of the condition, they all
      presented premature fusion of the coronal suture. Although none of them showed
      signs of cranial hypertension, one patient had had the craniosynostosis
      surgically corrected previously. These data suggest that the cranial sutures in
      pycnodysostosis can display contradictory features: wide cranial sutures, which
      are commonly described, and craniosynostosis. The clinical impact of this latter
      finding still remains to be elucidated. Further studies are necessary to address
      more precisely the role of cathepsin K in suture patency.

PMID- 20814952
TI  - Questions regarding conclusions reached in "age dependence of femoral strength in
      white women and men".

PMID- 20814954
TI  - Trends in incidence of subtrochanteric fragility fractures and bisphosphonate use
      among the US elderly, 1996-2007.
AB  - Increasing numbers of atypical hip fractures have been reported among patients
      with bisphosphonate use. However, the nature and extent of the problem are
      unknown despite recent investigations. To analyze national trends in hip
      fractures and medication use in the elderly US population, we respectively used
      the Nationwide Inpatient Sample (NIS) and the Medical Expenditure Panel Survey
      (MEPS) from 1996 to 2007. In NIS, subtrochanteric fragility fractures were
      compared with typical hip fractures in femoral neck and intertrochanteric
      regions. Between 1996 and 2007, age-adjusted rates for typical hip fractures
      decreased by 31.6% among women (from 1020.5 to 697.4 per 100,000 population) and
      20.5% among men (from 424.9 to 337.6 per 100,000 population). In contrast,
      overall trends in age-adjusted rates for subtrochanteric fragility fractures
      remained unchanged among men (p = .34) but increased 20.4% among women from 28.4
      (95% confidence interval [CI] 27.7-29.1) in 1999 to 34.2 (95% CI 33.4-34.9) per
      100,000 population in 2007. The annual percentage increase was 2.1% (95% CI 1.3
      2.8, p < .001) based on joinpoint regression analysis. In MEPS, bisphosphonate
      use increased predominantly in women (from 3.5% in 1996 to 16.6% in 2007)
      compared with men (2.3% in 2007). In the context of declining typical hip
      fractures among the US elderly, we observed small but significant increases in
      the incidence of subtrochanteric fragility fractures from 1999 among
      postmenopausal women. Using age-adjusted rates, we estimated that for every 100
      or so reduction in typical femoral neck or intertrochanteric fractures, there was
      an increase of one subtrochanteric fragility fracture.

PMID- 20814955
TI  - BMI and fracture risk in older men: the osteoporotic fractures in men study
      (MrOS).
AB  - Low body mass index (BMI) is a risk factor for fracture, but little is known
      about the association between high BMI and fracture risk. We evaluated the
      association between BMI and fracture in the Osteoporotic Fractures in Men Study
      (MrOS), a cohort of 5995 US men 65 years of age and older. Standardized measures
      included weight, height, and hip bone mineral density (BMD) by dual-energy X-ray
      absorptiometry (DXA); medical history; lifestyle; and physical performance. Only
      6 men (0.1%) were underweight (<18.5 kg/m(2)); therefore, men in this category
      were excluded. Also, 27% of men had normal BMI (18.5 to 24.9 kg/m(2)), 52% were
      overweight (25 to 29.9 kg/m(2)), 18% were obese I (30 to 34.9 kg/m(2)), and 3%
      were obese II (35 to 39.9 kg/m(2)). Overall, nonspine fracture incidence was 16.1
      per 1000 person-years, and hip fracture incidence was 3.1 per 1000 person-years.
      In age-, race-, and BMD-adjusted models, compared with normal weight, the hazard
      ratio (HR) for nonspine fracture was 1.04 [95% confidence interval (CI) 0.87
      1.25] for overweight, 1.29 (95% CI 1.00-1.67) for obese I, and 1.94 (95% CI 1.25
      3.02) for obese II. Associations were weaker and not statistically significant
      after adjustment for mobility limitations and walking pace (HR = 1.02, 95% CI
      0.84-1.23, for overweight; HR = 1.12, 95% CI 0.86-1.46, for obese I, and HR =
      1.44, 95% CI 0.90-2.28, for obese II). Obesity is common among older men, and
      when BMD is held constant, it is associated with an increased risk of fracture.
      This association is at least partially explained by worse physical function in
      obese men.

PMID- 20814956
TI  - Protein tyrosine phosphatase 1B inhibitors: a molecular level legitimate approach
      for the management of diabetes mellitus.
AB  - Diabetes mellitus is a systemic disease responsible for morbidity in the western
      world and is gradually becoming prevalent in developing countries too. The
      prevalence of diabetes is rapidly increasing in industrialized countries and type
      2 diabetes accounts for 90% of the disease. Insulin resistance is a major
      pathophysiological factor in the development of type 2 diabetes, occurring mainly
      in muscle, adipose tissues, and liver leading to reduced glucose uptake and
      utilization and increased glucose production. The prevalence and rising incidence
      of diabetes emphasized the need to explore new molecular targets and strategies
      to develop novel antihyperglycemic agents. Protein Tyrosine Phosphatase 1B (PTP
      1B) has recently emerged as a promising molecular level legitimate therapeutic
      target in the effective management of type 2 diabetes. PTP 1B, a cytosolic
      nonreceptor PTPase, has been implicated as a negative regulator of insulin signal
      transduction. Therefore, PTP 1B inhibitors would increase insulin sensitivity by
      blocking the PTP 1B-mediated negative insulin signaling pathway and might be an
      attractive target for type 2 diabetes mellitus and obesity. With X-ray
      crystallography and NMR-based fragment screening, the binding interactions of
      several classes of inhibitors have been elucidated, which could help the design
      of future PTP 1B inhibitors. The drug discovery research in PTP 1B is a
      challenging area to work with and many pharmaceutical organizations and academic
      research laboratories are focusing their research toward the development of
      potential PTP 1B inhibitors which would prove to be a milestone for the
      management of diabetes.

PMID- 20814957
TI  - Peptide-mediated targeted drug delivery.
AB  - Targeted drug delivery to specific group of cells offers an attractive strategy
      to minimize the undesirable side effects and achieve the therapeutic effect with
      a lower dose. Both linear and cyclic peptides have been explored as trafficking
      moiety due to ease of synthesis, structural simplicity, and low probability of
      undesirable immunogenicity. Peptides derived from sequence of cell surface
      proteins, such as intercellular adhesion molecule-1 (ICAM-1), LHRH, Bombesin, and
      LFA-1, have shown potent binding affinity to the target cell surface receptors.
      Moreover, peptides derived from ICAM-1 receptor can be internalized by the
      leukemic T-cells along with the conjugated moiety offering the promise to
      selectively treat cancers and autoimmune diseases. Systematic analyses have
      revealed that physicochemical properties of the drug-peptide conjugates and their
      mechanism of receptor-mediated cellular internalization are important controlling
      factors for developing a successful targeting system. This review is focused on
      understanding the factors involved in the development of an effective drug
      peptide conjugate with an emphasis on the chemistry and biology of the
      conjugates. Reported results on several promising drug-peptide conjugates have
      been critically evaluated. The approaches and results presented here will serve
      as a guide to systematically approach targeted delivery of cytotoxic drug
      molecules using peptides for treatment of several diseases.

PMID- 20814958
TI  - Insights into the targeted elimination of BRCA1-defective cancer stem cells.
AB  - BRCA1 expression is involved in normal embryonic development, mammary stem cell
      differentiation, and prostate cancer development. Inactivation of BRCA1 plays an
      important role in cancer stem cells and also leads to the development of high
      grade, basal-like tumor. This review discusses why BRCA1-defective cancer stem
      cells need a prospective analysis, how ER alpha could influence BRCA1-defective
      tumor progression, phenotype of BRCA1-defective cancers, role of BRCA1 in other
      cancers and finally at what perspective BRCA1-defective cancers can be targeted
      for better therapeutic outcome.

PMID- 20814959
TI  - Discovering the somatotopic organization of the motor areas of the medial wall
      using low-frequency BOLD fluctuations.
AB  - This study explored the somatotopy of the motor areas of the medial wall of the
      cerebral hemisphere, in the human brain. In a sample of 16 healthy participants,
      we drew 9 regions of interest (ROI) over the primary motor area (M1), each
      corresponding to a well-known somatic representation. Using functional magnetic
      resonance imaging, we investigated the resting state functional connectivity
      between each selected ROI and the motor areas of the medial wall. The main
      finding was the identification of a rostrocaudal gradient of connectivity in
      which the more we move from cranial to caudal body representation areas in M1,
      the more the corresponding connected area in the medial wall is shifted
      rostrocaudally, confirming the somatotopic schema found in the SMA. We also
      reanalyzed data obtained in a previous experiment, we performed using hand and
      foot motor tasks; the reanalysis consisted in traditional BOLD and functional
      connectivity analyses. Finally, we performed a meta-analysis of 28 studies of
      hand and foot motor tasks, mapping their cerebral representations using the tools
      provided by the Brainmap database. All data converge in confirming a somatotopic
      representation of the medial wall motor areas, with hand representation placed
      more rostrally and ventrally than that of the foot.

PMID- 20814961
TI  - Dynamic changes in functional cerebral connectivity of spatial cognition during
      the menstrual cycle.
AB  - Functional cerebral asymmetries (FCAs) in women have been shown to vary with
      changing levels of sex hormones during the menstrual cycle. Previous studies have
      suggested that interhemispheric interaction forms a key component in generating
      FCAs and it has been shown behaviorally and by functional imaging that
      interhemispheric interaction changes during the menstrual cycle, at least for a
      left hemisphere dominant task. We used functional MRI and an analysis of
      functional connectivity to examine whether changes in right hemisphere advantage
      for a figure comparison task as found in behavioral studies, are based on
      comparable mechanisms like those identified for the verbal task. Women were
      examined three times during the menstrual cycle, during the menstrual, follicular
      and luteal phases. The behavioral data confirmed the right hemisphere advantage
      for the figure comparison task as well as changes of the right hemisphere
      advantage during the menstrual cycle. Imaging data showed cycle phase-related
      changes in lateralized brain activation within the task-dominant hemisphere and
      changes in connectivity between nonhomotopic areas of both hemispheres,
      suggesting that changes in functional brain organization in women during the
      menstrual cycle are not only restricted to hormone-related changes of
      interhemispheric inhibition between homotopic areas, as has been proposed
      earlier, but might additionally apply to changes of neuronal processes within the
      hemispheres which seem to be modulated by heterotopic functional connectivity
      between hemispheres.

PMID- 20814962
TI  - Spectral loudness summation takes place in the primary auditory cortex.
AB  - Auditory functional magnetic resonance imaging (fMRI) was used to assess neural
      activation in the human auditory brainstem (AB) and cortex (AC) as a function of
      bandwidth (BW). We recorded brain activation of 22 normal hearing listeners
      induced by band pass filtered pink noise stimuli with equal sound pressure level
      of 70 dB SPL. Tested bandwidths were 50, 500, 1,500, 3,000, 6,000, and 8,000 Hz.
      The center frequency was 4,000 Hz. Categorical loudness scaling had been
      performed in a silent booth with all of these stimuli. Loudness as a function of
      bandwidth followed a concave-shaped curve which reflected the influence of
      spectral loudness summation (SLS) for higher BW and the influence of large
      amplitude fluctuations for very low BW, which itself could be explained by peak
      listening. While neural activation of the AB, as measured by the percent signal
      change from baseline (PSC), was tuned to the physical BW of the stimuli in a
      straight linear fashion, the trend of perceived loudness as a function of BW was
      reflected in several aspects by corresponding neural activation in the primary
      auditory cortex (PAC). Finally, from the absolute differences of the PSC between
      PAC and AB, gains in perceived loudness associated with SLS and the effect of
      large amplitude fluctuations could be predicted with an accuracy of 1-2 dB for
      the whole group of participants.

PMID- 20814960
TI  - Regional and hemispheric determinants of language laterality: implications for
      preoperative fMRI.
AB  - Language is typically a function of the left hemisphere but the right hemisphere
      is also essential in some healthy individuals and patients. This inter-subject
      variability necessitates the localization of language function, at the individual
      level, prior to neurosurgical intervention. Such assessments are typically made
      by comparing left and right hemisphere language function to determine "language
      lateralization" using clinical tests or fMRI. Here, we show that language
      function needs to be assessed at the region and hemisphere specific level,
      because laterality measures can be misleading. Using fMRI data from 82 healthy
      participants, we investigated the degree to which activation for a semantic word
      matching task was lateralized in 50 different brain regions and across the entire
      cortex. This revealed two novel findings. First, the degree to which language is
      lateralized across brain regions and between subjects was primarily driven by
      differences in right hemisphere activation rather than differences in left
      hemisphere activation. Second, we found that healthy subjects who have relatively
      high left lateralization in the angular gyrus also have relatively low left
      lateralization in the ventral precentral gyrus. These findings illustrate spatial
      heterogeneity in language lateralization that is lost when global laterality
      measures are considered. It is likely that the complex spatial variability we
      observed in healthy controls is more exaggerated in patients with brain damage.
      We therefore highlight the importance of investigating within hemisphere regional
      variations in fMRI activation, prior to neuro-surgical intervention, to determine
      how each hemisphere and each region contributes to language processing.

PMID- 20814963
TI  - Repetition suppression in occipitotemporal cortex despite negligible visual
      similarity: evidence for postperceptual processing?
AB  - The reduced neural response in certain brain regions when a task-relevant
      stimulus is repeated ("repetition suppression", RS) is often attributed to
      facilitation of the cognitive processes performed in those regions. Repetition of
      visual objects is associated with RS in the ventral and lateral
      occipital/temporal regions, and is typically attributed to facilitation of visual
      processes, ranging from the extraction of shape to the perceptual identification
      of objects. In two fMRI experiments using a semantic classification task, we
      found RS in a left lateral occipital/inferior temporal region to a picture of an
      object when the name of that object had previously been presented in a separate
      session. In other words, we found RS despite negligible visual similarity between
      the initial and repeated occurrences of an object identity. There was no evidence
      that this RS was driven by the learning of task-specific responses to an object
      identity ("S-R learning"). We consider several explanations of this
      occipitotemporal RS, such as phonological retrieval, semantic retrieval, and
      visual imagery. Although no explanation if fully satisfactory, it is proposed
      that such effects most plausibly relate to the extraction of task-relevant
      information relating to object size, either through the extraction of sensory
      specific semantic information or through visual imagery processes. Our findings
      serve to emphasize the potential complexity of processing within traditionally
      visual regions, at least as measured by fMRI.

PMID- 20814964
TI  - fMRI functional networks for EEG source imaging.
AB  - The brain exhibits temporally coherent networks (TCNs) involving numerous
      cortical and sub-cortical regions both during the rest state and during the
      performance of cognitive tasks. TCNs represent the interactions between different
      brain areas, and understanding such networks may facilitate
      electroencephalography (EEG) source estimation. We propose a new method for
      examining TCNs using scalp EEG in conjunction with data obtained by functional
      magnetic resonance imaging (fMRI). In this approach, termed NEtwork based SOurce
      Imaging (NESOI), multiple TCNs derived from fMRI with independent component
      analysis (ICA) are used as the covariance priors of the EEG source reconstruction
      using Parametric Empirical Bayesian (PEB). In contrast to previous applications
      of PEB in EEG source imaging with smoothness or sparseness priors, TCNs play a
      fundamental role among the priors used by NESOI. NESOI achieves an efficient
      integration of the high temporal resolution EEG and TCN derived from the high
      spatial resolution fMRI. Using synthetic and real data, we directly compared the
      performance of NESOI with other distributed source inversion methods, with and
      without the use of fMRI priors. Our results indicated that NESOI is a potentially
      useful approach for EEG source imaging.

PMID- 20814965
TI  - Simple questionnaire for assessing core outcomes in inguinal hernia repair.
AB  - BACKGROUND: Patient-oriented questionnaires are indispensable in the assessment
      of surgical outcome. The psychometric properties of a brief multidimensional
      instrument were examined in patients with inguinal hernia undergoing surgery.
      METHODS: Fifty-one patients (mean(s.d.) age 50.6(17.4) years; 48 men)
      participated. The following questionnaire properties were assessed for the Core
      Outcome Measures Index adapted for patients with hernia (COMI-hernia) and the
      EuroQol: practicability, floor and ceiling effects, test-retest reliability (over
      2 weeks), construct validity (by comparison with other relevant scales) and
      responsiveness 9 months after surgery as standardized response mean (SRM).
      RESULTS: The questionnaires were easy to implement and well accepted by the
      patients. Ceiling effects at baseline were 2 per cent for the COMI-hernia, 8 per
      cent for EuroQol-visual analogue scale (EQ-VAS) and 35 per cent for EuroQol-Five
      Dimensions (EQ-5D); no instrument showed floor effects. The reproducibility of
      individual COMI-hernia items was good, with test-retest differences within one
      grade ranging from 41 of 45 for 'social/work disability' to 44 of 45 for 'general
      quality of life'. The intraclass correlation coefficients were moderately high
      for COMI-hernia (0.74) and EQ-VAS (0.77), but low for EQ-5D (0.43). COMI-hernia
      scores correlated in the expected manner with related scales (r = 0.42-0.72, P <
      0.050). COMI-hernia was the most responsive instrument (SRM 1.42). CONCLUSION:
      The COMI-hernia and EQ-VAS general health scale represent reliable, valid and
      sensitive tools for assessing multidimensional outcome in patients with inguinal
      hernia undergoing surgical treatment.

PMID- 20814966
TI  - Finite element modelling of maxillofacial surgery and facial expressions--a
      preliminary study.
AB  - BACKGROUND: Recent advances in diagnostic imaging and associated software have
      enabled the transformation of anatomical structures into finite element (FE)
      models facilitating computerized facial modelling. The work presented employs
      personalized imaging data of facial anatomical structures for use in planning and
      predicting the outcome of maxillofacial surgery. The current process relies on
      either freehand planning and/or commercial two-dimensional (2D) and three
      dimensional (3D) surgical planning software packages, but the validity of these
      software packages has been questioned. In this paper, the finite element
      technique was used to predict the outcome of maxillofacial surgery. METHODS: A
      finite element facial model was created, based on patient specific bone and skin
      image data, combined with generic muscle data. The model was used for two
      distinct purposes: simulation of the maxillofacial surgery and simulation of
      facial expressions pre- and post-surgery. This combination allowed for an
      improved prediction of surgery outcome. Commercial software was used for creating
      the FE facial model from the original image data, and LS-DYNA((r)) was the
      analysis code used for the purpose of the FE simulation. RESULTS: The results
      from the simulation of maxillofacial surgery showed an overall agreement of 85%
      with the patient data at 6 months post-surgery and the error was generally
      contained within a +/- 2 mm threshold. CONCLUSIONS: The results show that the
      approach of using commercial FE software tools to create a detailed and
      anatomically accurate patient specific model for simulation of maxillofacial
      surgery, as well as facial expressions, can be applied in facial surgery
      planning. As the study was based on data collected from one patient, further work
      is needed in which additional subjects can be assessed.

PMID- 20814967
TI  - Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1
      34)] in postmenopausal osteoporosis.
AB  - Clinical data suggest concomitant therapy with bisphosphonates and parathyroid
      hormone (PTH) may blunt the anabolic effect of PTH; rodent models suggest that
      infrequently administered bisphosphonates may interact differently. To evaluate
      the effects of combination therapy with an intravenous infusion of zoledronic
      acid 5 mg and daily subcutaneous recombinant human (rh)PTH(1-34) (teriparatide)
      20 ug versus either agent alone on bone mineral density (BMD) and bone turnover
      markers, we conducted a 1-year multicenter, multinational, randomized, partial
      double-blinded, controlled trial. 412 postmenopausal women with osteoporosis
      (mean age 65 +/- 9 years) were randomized to a single infusion of zoledronic acid
      5 mg plus daily subcutaneous teriparatide 20 ug (n = 137), zoledronic acid alone
      (n = 137), or teriparatide alone (n = 138). The primary endpoint was percentage
      increase in lumbar spine BMD (assessed by dual-energy X-ray absorptiometry [DXA])
      at 52 weeks versus baseline. Secondary endpoints included change in BMD at the
      spine at earlier time points and at the total hip, trochanter, and femoral neck
      at all time points. At week 52, lumbar spine BMD had increased 7.5%, 7.0%, and
      4.4% in the combination, teriparatide, and zoledronic acid groups, respectively
      (p < .001 for combination and teriparatide versus zoledronic acid). In the
      combination group, spine BMD increased more rapidly than with either agent alone
      (p < .001 versus both teriparatide and zoledronic acid at 13 and 26 weeks).
      Combination therapy increased total-hip BMD more than teriparatide alone at all
      times (all p < .01) and more than zoledronic acid at 13 weeks (p < .05), with
      final 52-week increments of 2.3%, 1.1%, and 2.2% in the combination,
      teriparatide, and zoledronic acid groups, respectively. With combination therapy,
      bone formation (assessed by serum N-terminal propeptide of type I collagen
      [PINP]) increased from 0 to 4 weeks, declined minimally from 4 to 8 weeks, and
      then rose throughout the trial, with levels above baseline from 6 to 12 months.
      Bone resorption (assessed by serum beta-C-telopeptide of type I collagen [beta
      CTX]) was markedly reduced with combination therapy from 0 to 8 weeks (a
      reduction of similar magnitude to that seen with zoledronic acid alone), followed
      by a gradual increase after week 8, with levels remaining above baseline for the
      latter half of the year. Levels for both markers were significantly lower with
      combination therapy versus teriparatide alone (p < .002). Limitations of the
      study included its short duration, lack of endpoints beyond DXA-based BMD (e.g.,
      quantitative computed tomography and finite-element modeling for bone strength),
      lack of teriparatide placebo, and insufficient power for fracture outcomes. We
      conclude that while teriparatide increases spine BMD more than zoledronic acid
      and zoledronic acid increases hip BMD more than teriparatide, combination therapy
      provides the largest, most rapid increments when both spine and hip sites are
      considered.

PMID- 20814968
TI  - Calpain-6, a target molecule of glucocorticoids, regulates osteoclastic bone
      resorption via cytoskeletal organization and microtubule acetylation.
AB  - Glucocorticoids (GCs) inhibit the resorptive capacity of the osteoclast by
      disrupting its cytoskeleton. We find that calpain-6 (Capn6), a unique,
      nonproteolytic member of its family, is suppressed 12-fold by dexamethasone (DEX)
      in the bone-degrading cell. While Capn6 abundance parallels commitment of naive
      bone marrow macrophages (BMMs) to the osteoclast phenotype, its excess or
      deletion does not affect the cell's differentiation. On the other hand, Capn6
      localizes to the sealing zone, and its overexpression promotes osteoclast
      spreading and large actin ring formation, eventuating in stimulated bone
      degradation. Conversely, Capn6 knockdown impairs cytoskeletal organization and
      the cell's resorptive capacity. Capn6 complexes with tubulin, and its absence
      inhibits microtubule acetylation and stability in the osteoclast. Knockdown of
      Capn6 also reduces beta(3)-integrin subunit protein, another essential regulator
      of osteoclast cytoskeletal function. Reflecting Capn6 as a target molecule of
      GCs, microtubule stability and acetylation, as well as the expression of beta(3)
      integrin protein, are similarly suppressed in DEX-treated osteoclasts. Moreover,
      overexpression of Capn6 rescues GC-mediated disruption of osteoclast
      cytoskeleton. Thus Capn6 promotes cytoskeletal organization and microtubule
      stability in osteoclasts, and its inhibition may mediate the resorption-arresting
      properties of GCs.

PMID- 20814969
TI  - Perlecan/Hspg2 deficiency alters the pericellular space of the lacunocanalicular
      system surrounding osteocytic processes in cortical bone.
AB  - Osteocytes project long, slender processes throughout the mineralized matrix of
      bone, where they connect and communicate with effector cells. The interconnected
      cellular projections form the functional lacunocanalicular system, allowing fluid
      to pass for cell-to-cell communication and nutrient and waste exchange.
      Prevention of mineralization in the pericellular space of the lacunocanalicular
      pericellular space is crucial for uninhibited interstitial fluid movement.
      Factors contributing to the ability of the pericellular space of the
      lacunocanalicular system to remain open and unmineralized are unclear.
      Immunofluorescence and immunogold localization by transmission electron
      microscopy demonstrated perlecan/Hspg2 signal localized to the osteocyte
      lacunocanalicular system of cortical bone, and this proteoglycan was found in the
      pericellular space of the lacunocanalicular system. In this study we examined
      osteocyte lacunocanalicular morphology in mice deficient in the large heparan
      sulfate proteoglycan perlecan/Hspg2 in this tissue. Ultrastructural measurements
      with electron microscopy of perlecan/Hspg2-deficient mice demonstrated diminished
      osteocyte canalicular pericellular area, resulting from a reduction in the total
      canalicular area. Additionally, perlecan/Hspg2-deficient mice showed decreased
      canalicular density and a reduced number of transverse tethering elements per
      canaliculus. These data indicated that perlecan/Hspg2 contributed to the
      integrity of the osteocyte lacunocanalicular system by maintaining the size of
      the pericellular space, an essential task to promote uninhibited interstitial
      fluid movement in this mechanosensitive environment. This work thus identified a
      new barrier function for perlecan/Hspg2 in murine cortical bone.

PMID- 20814970
TI  - Comparison of intravenous and intramuscular neridronate regimens for the
      treatment of Paget disease of bone.
AB  - Aminobisphosphonates actually represent the most common treatment for Paget
      disease of bone (PDB). In a previous study we demonstrated that either zoledronic
      acid (4 mg) or neridronate (200 mg) given as a single intravenous infusion showed
      a similar short-term efficacy in achieving biochemical remission in up to 90% of
      patient nonresponders to pamidronate. In this study we compared the long-term (36
      months) effects of a same neridronate dose (200 mg) given as an intravenous (100
      mg infusion for 2 consecutive days) or intramuscular (25-mg injection weekly for
      2 months) regimen in 56 patients with active PDB. All patients were advised to
      receive calcium plus vitamin D supplementation throughout the study period. At 6
      months, 92.6% and 96.5% of patients receiving intravenous and intramuscular
      neridronate, respectively, achieved a therapeutic response [defined as
      normalization of alkaline phosphatase (ALP) levels or a reduction of at least 75%
      in total ALP excess]. The response to treatment was significantly correlated with
      baseline ALP and 25-hydroxyvitamin D [25(OH)D] levels at 6 months. The decrease
      in ALP levels was highest in patients with higher baseline total or bone-specific
      ALP levels and with higher 25(OH)D levels at 6 months. Response rates were
      maintained at 12 months but decreased progressively at 24 and 36 months without
      significant differences between the two neridronate regimens. Both regimens were
      well tolerated. The only relevant side effect was an acute-phase response
      occurring in 14% of the patients. In conclusion, these results indicate that a
      200-mg intramuscular neridronate course has a similar efficacy as an intravenous
      infusion of the same dose for the treatment of PDB and might be of particular
      value for patients intolerant to oral bisphosphonates and unwilling or unable to
      undergo intravenous infusions.

PMID- 20814971
TI  - Abnormal bone remodeling in patients with spontaneous painful vertebral fracture.
AB  - The application of tetracycline-based iliac bone histomorphometry to the study of
      the pathogenesis of osteoporosis has given conflicting results. Accordingly, we
      performed this procedure in 78 postmenopausal white women with one or more
      vertebral fractures identified according to rigorous criteria that excluded other
      causes of vertebral deformity and 66 healthy postmenopausal white women recruited
      from the same geographic region; the groups did not differ in age or weight. In
      each subject, measurements were made separately on the cancellous (Cn),
      endocortical (Ec), and intracortical (Ct) subdivisions of the endosteal envelope.
      In the fracture patients, osteoblast surface was reduced substantially on each
      subdivision, most markedly on the Cn surface, where about 25% of the deficit was
      in cuboidal (type II) osteoblasts, suggesting impaired recruitment; the remaining
      75% of the deficit was in intermediate (type III) cells, suggesting earlier
      transition from type III to type IV (flat) cells. On the Ec and Ct surfaces, the
      deficit was exclusively in type III cells. Mean bone formation rate was reduced
      by about 18% on the Cn but not on the Ec or Ct surfaces. The deficit was more
      significant in subjects matched for Cn BV/TV when adjusted for the inverse
      regression on osteocyte density and after logarithmic transformation. The
      difference in bone formation rate resulted from a corresponding reduction in wall
      thickness without a change in activation frequency. The frequency distribution of
      bone formation rate was more skewed to the left in the fracture patients than in
      the controls. Osteoclast surface was significantly lower on each subdivision. The
      variation in osteoblast surface, bone formation rate, and osteoclast surface was
      significantly greater in the fracture patients than in the controls, with more
      abnormally low and abnormally high values. The data suggest the following
      conclusions: (1) The histologic heterogeneity of postmenopausal osteoporosis is
      reaffirmed; (2) the different subdivisions of the endosteal envelope, although in
      continuity, behave differently in health and disease; (3) a combination of
      defective osteoblast recruitment and premature osteoblast apoptosis would account
      for the deficit in type II and III cells and the reductions in wall thickness and
      bone formation rate on the Cn surface and the previously reported osteocyte
      deficiency in Cn bone; (4) premature disaggregation of multinuclear to
      mononuclear resorbing cells could account for the osteoclast deficit; and (5)
      some patients with vertebral fracture have one or another disorder of bone
      remodeling that at present cannot be identified by noninvasive means.

PMID- 20814973
TI  - Prosocial/hostile roles and emotion comprehension in preschoolers.
AB  - Bullying occurs at approximately the same rate in kindergarten as in elementary
      school, but few studies inquired into preschool years [Alsaker and Nagele, 2008;
      Stassen Berger, 2007]. This study aimed at: (1) verifying the presence in
      preschoolers of two additional participant roles (Consoler and Mediator), besides
      the six traditional roles detected by Salmivalli et al. [1996], grouped in four
      latent macroroles, by means of teacher report version of the Eight Participant
      Roles Questionnaire (PRQ) [Belacchi, 2008]; (2) linking prosocial and hostile
      behaviors to age and gender; and (3) investigating the relationship between roles
      and emotion understanding. Two hundred and nineteen children (54% boys; aged 3-6
      years: mean age 4;10) were administered the Italian version of the Test of
      Emotion Comprehension [Albanese and Molina, 2008]; 20 teachers (2 for each class)
      filled in the questionnaire, attributing frequency scores on 24 items (3 for each
      role) to each pupil. A confirmatory analysis supported the fit of the hetero
      report version of the Eight PRQ, revealing four macroroles: Hostile Roles (Bully,
      Reinforcer and Assistant), Prosocial Roles (Defender, Consoler, and Mediator),
      Victim, and Outsider. Satisfactory interteachers agreement not only confirms the
      macroroles hypothized, but also their expected distribution for gender and age.
      Moreover, the Prosocial roles presented a significant positive correlation with
      all subdimensions of emotion comprehension (External, Mental, and Reflective).
      The Victim and Outsider roles negatively correlated only with the External
      subdimension. The implications of these results for prevention and intervention
      purposes are discussed.

PMID- 20814972
TI  - Maslinic acid suppresses osteoclastogenesis and prevents ovariectomy-induced bone
      loss by regulating RANKL-mediated NF-kappaB and MAPK signaling pathways.
AB  - Activation of NF-kappaB and MAPK/activator protein 1 (AP-1) signaling pathways by
      receptor activator NF-kappaB ligand (RANKL) is essential for osteoclast activity.
      Targeting NF-kappaB and MAPK/AP-1 signaling to modulate osteoclast activity has
      been a promising strategy for osteoclast-related diseases. In this study we
      examined the effects of maslinic acid (MA), a pentacyclic triterpene acid that is
      widely present in dietary plants, on RANKL-induced osteoclastogenesis, osteoclast
      function, and signaling pathways by in vitro and in vivo assay systems. In mouse
      bone marrow monocytes (BMMs) and RAW264.7 cells, MA inhibited RANKL-induced
      osteoclastogenesis in a dose-dependent manner within nongrowth inhibitory
      concentration, and MA decreased osteoclastogenesis-related marker gene
      expression, including TRACP, MMP9, c-Src, CTR, and cathepsin K. Specifically, MA
      suppressed osteoclastogenesis and actin ring formation at early stage. In
      ovariectomized mice, administration of MA prevented ovariectomy-induced bone loss
      by inhibiting osteoclast activity. At molecular levels, MA abrogated the
      phosphorylation of MAPKs and AP-1 activity, inhibited the IkappaBalpha
      phosphorylation and degradation, blocked NF-kappaB/p65 phosphorylation, nuclear
      translocation, and DNA-binding activity by downregulating RANK expression and
      blocking RANK interaction with TRAF6. Together our data demonstrate that MA
      suppresses RANKL-induced osteoclastogenesis through NF-kappaB and MAPK/AP-1
      signaling pathways and that MA is a promising agent in the treatment of
      osteoclast-related diseases such as osteoporosis.

PMID- 20814974
TI  - Memory-efficient calculation of the isotopic mass states of a molecule.
AB  - Our previous work postulated a transition concept among different isotopic mass
      states (i.e., isotopic species) of a molecule, and developed a hierarchical
      algorithm for accurately calculating their masses and abundances. A theoretical
      mass spectrum can be generated by convoluting a peak shape function to these
      discrete mass states. This approach suffers from limited memory if a level in the
      hierarchical structure has too many mass states. Here we present a memory
      efficient divide-and-recursively-combine algorithm to do the calculation, which
      also improves the truncation method used in the previous hierarchical algorithm.
      Instead of treating all of the elements in a molecule as a whole, the new
      algorithm first 'strips' each element one by one. For the mass states of each
      element, a hierarchical structure is established and kept in the memory. This
      process reduces the memory usage by orders of magnitude (e.g., for bovine
      insulin, memory can be reduced from gigabytes to kilobytes). Next, a recursive
      algorithm is applied to combine mass states of elements to mass states of the
      whole molecule. The algorithm described above has been implemented as a computer
      program called Isotope Calculator, which was written in C++. It is freely
      available under the GNU Lesser General Public License from
      http://www.cs.brandeis.edu/~hong/software.html or
      http://people.brandeis.edu/~agar.

PMID- 20814975
TI  - Error propagation in normalization of stable isotope data: a Monte Carlo
      analysis.
AB  - A higher analytical precision of a stable isotope ratio mass spectrometer does
      not automatically guarantee accurate determination of the true isotope
      composition (delta-value) of samples, since estimates of true delta-values are
      obtained from the normalization of raw isotope data. We performed both Monte
      Carlo simulations and laboratory experiments to investigate aspects of error
      propagation during the normalization of carbon stable isotope data. We found that
      increasing both the number of different reference standards and the number of
      repetitions of each of these standards reduces the normalization error. A 50%
      reduction in the normalization error can be achieved over the two-point
      normalization by either analyzing two standards four times each, or four
      standards two times each. If the true delta-value of a sample is approximately
      known a priori, the normalization error may then be reduced through a targeted
      choice of locally optimal standards. However, the difference in improvement is
      minimal and, therefore, a more practical strategy is to use two or more standards
      covering the whole stable isotope scale. The selection of different sets of
      standards by different laboratories or for different batches of samples in the
      same laboratory may lead to significant differences in the normalized delta
      values of the same samples, leading to inconsistent results. Hence, the same set
      of standards should always be used for a particular element and a particular
      stable isotope analytical technique.

PMID- 20814976
TI  - Toxicological determination and in vitro metabolism of the designer drug
      methylenedioxypyrovalerone (MDPV) by gas chromatography/mass spectrometry and
      liquid chromatography/quadrupole time-of-flight mass spectrometry.
AB  - A method for the toxicological screening of the new designer drug
      methylenedioxypyrovalerone (MDPV) is described; with an emphasis on its
      application for anti-doping analysis. The metabolism of MDPV was evaluated in
      vitro using human liver microsomes and S9 cellular fractions for CYP450 phase I
      and uridine 5'-diphosphoglucuronosyltransferase (UGT) and sulfotransferase (SULT)
      phase II metabolism studies. The resulting metabolites were subsequently
      liquid/liquid extracted and analyzed using gas chromatography/mass spectrometry
      (GC/MS) as trimethylsilyl (TMS) derivatives. The structures of the metabolites
      were further confirmed by accurate mass measurement using a liquid
      chromatography/quadrupole time-of-flight (LC/QTOF) mass spectrometer. The studies
      demonstrated that the main metabolites of MDPV are catechol and methyl catechol
      pyrovalerone, which are in turn sulfated and glucuronated. The method for the
      determination of MDPV in urine has been fully validated by assessing the limits
      of detection and quantification, linearity, repeatability, and accuracy. This
      validation demonstrates the suitability for screening of this stimulant substance
      for anti-doping and forensic toxicology purposes.

PMID- 20814977
TI  - Marked difference in fragmentation between collision-induced excitation and chemi
      excitation of keto esters produced from dioxetanes bearing a 4-(benzothiazol-2
      yl)-3-hydroxyphenyl moiety in negative-mode matrix-assisted laser
      desorption/ionization time-of-flight tandem mass spectrometry.
AB  - A dioxetane bearing a hydroxyphenyl group produces an unstable oxidoaryl anion by
      deprotonation which rapidly decomposes with accompanying emission of light
      effectively by the intramolecular charge-transfer-induced decomposition (CTID)
      mechanism. Although several mechanisms have been proposed to explain chemi
      excitation in CTID, strong experimental evidence is still lacking. In the course
      of our investigation to clarify the chemi-excitation process, negative-mode
      matrix-assisted laser desorption/ionization time-of-flight collision-induced
      dissociation tandem mass spectrometry (MALDI-TOF-CID-MS/MS) was used to
      investigate the decomposition of bicyclic dioxetanes bearing a 4-(benzothiazol-2
      yl)-3-hydroxyphenyl moiety 1 and their related keto esters 2 in a gas phase.
      Dioxetanes 1 decomposed to give 2 in an electronically excited state, which
      underwent alpha-cleavage of a ketone moiety, while authentic 2 (ground state)
      hardly showed fragmentation in MS. On the other hand, 2 displayed fragment ions
      in CID-MS/MS, though the fragmentation pattern was significantly different
      between 2a (R = tert-butyl) and 2b-2d (R = isopropyl, ethyl and methyl,
      respectively): 2a exhibited mainly alpha-cleavage of a ketone moiety, while 2b-2d
      showed beta-cleavage of the aromatic ester moiety. The marked difference in
      fragmentation between 2 (electronically excited state) produced directly from 1
      and authentic 2 under CID was most likely due to the difference in the excitation
      processes: chemi-excitation of 2 by CTID of 1 versus vibrational excitation of 2
      induced by collision in MS/MS.

PMID- 20814978
TI  - Application of imaging mass spectrometry for the analysis of Oryza sativa rice.
AB  - Rice is one of the most important food crops in the world and new varieties have
      been bred for specific purposes, such as the development of drought-resistance,
      or the enrichment of functional food factors. The localization and composition of
      metabolites in such new varieties must be investigated because all artificial
      interventions are expected to change the metabolites of rice. Imaging mass
      spectrometry using matrix-assisted laser desorption/ionization (MALDI-IMS) is a
      suitable tool for investigating the localization and composition of metabolites;
      however, suitable methodologies for the MALDI-IMS analysis of rice have not yet
      been established. In this study, we optimized the methods for analyzing rice
      grains by MALDI-IMS using adhesive film and found the characteristic distribution
      of metabolites in rice. Lysophosphatidylcholine (LPC) was localized in the
      endosperm. Phosphatidylcholine (PC), gamma-oryzanol and phytic acid were
      localized in the bran (germ and seed coat), and alpha-tocopherol was distributed
      in the germ (especially in the scutellum). In addition, MALDI-IMS revealed the
      LPC and PC composition of the rice samples. The LPC composition, LPC (1-acyl
      16:0), LPC (1-acyl 18:2), LPC (1-acyl 18:1) and LPC (1-acyl 18:0), was 59.4 +/-
      4.5%, 19.6 +/- 2.5%, 14.2 +/- 4.5% and 6.8 +/- 1.4%. The PC composition, PC
      (diacyl 16:0/18:2), PC (diacyl 16:0/18:1), PC (diacyl 18:1/18:3), PC (diacyl
      18:1/18:2) and PC (diacyl 18:1/18:2), was 19.6 +/- 1.0%, 21.0 +/- 1.0%, 15.0 +/-
      1.4%, 26.7 +/- 0.7% and 17.8 +/- 1.9%. This approach can be applied to the
      assessment of metabolites not only in rice, but also in other foods for which the
      preparation of sections is a challenging task.

PMID- 20814979
TI  - Metal displacement and stoichiometry of protein-metal complexes under native
      conditions using capillary electrophoresis/mass spectrometry.
AB  - Increases in the study of protein-metal complexes, as well as in metal
      displacement in protein-metal complexes under native conditions for optimum
      catalytic properties in drug research and catalyst design, demands a
      separation/detection technology that can accurately measure metal displacement
      and stoichiometry in protein-metal complexes. Both nuclear magnetic resonance
      (NMR) and X-ray diffraction techniques have been used for this purpose; however,
      these techniques lack sensitivity. Electrospray ionization mass spectrometry (ESI
      MS) using direct infusion offers higher sensitivity than the former techniques
      and provides molecular distribution of various protein-metal complexes. However,
      since protein-metal complexes under native conditions usually are dissolved in
      salt solutions, their direct ESI-MS analysis requires off-line sample clean-up
      prior to MS analysis to avoid sample suppression during ESI. Moreover, direct
      infusion of the salty solution promotes non-specific salt adduct formation by the
      protein-metal complexes under ESI-MS, which complicates the identification and
      stoichiometry measurements of the protein-metal complexes. Because of the high
      mass of protein-metal complexes and lack of sufficient resolution by most mass
      spectrometers to separate non-specific from specific metal-protein complexes,
      accurate protein-metal stoichiometry measurements require some form of sample
      clean up prior to ESI-MS analysis. In this study, we demonstrate that capillary
      electrophoresis/electrospray ionization in conjunction with a medium-resolution
      (approximately 10,000) mass spectrometer is an efficient and fast method for the
      measurement of the stoichiometry of the protein-metal complexes under
      physiological conditions (pH approximately 7). The metal displacement of Co(2+)
      to Cd(2+), two metal ions necessary for activation in the monomeric AHL lactonase
      produced by B. thuringiensis, has been used as a proof of concept.

PMID- 20814981
TI  - Quantitative analysis of positional isomers of triacylglycerols via electrospray
      ionization tandem mass spectrometry of sodiated adducts.
AB  - Herein we report a reversed-phase high-performance liquid chromatography tandem
      mass spectrometry (RP-HPLC/MS/MS) method for the analysis of positional isomers
      of triacylglycerols (TAGs) in vegetable oils. The fragmentation behavior of [M +
      X](+) ions (X = NH(4), Li, Na or Ag) was studied on a quadrupole-time-of-flight
      (Q-TOF) mass spectrometer under low-energy collision-induced dissociation (CID)
      conditions. Mass spectra that were dependent on the X(+) ion and the nature and
      position of the acyl substituents were observed for four pairs of 'AAB/ABA'-type
      TAGs, namely PPO/POP, OOP/OPO, LLO/LOL and OOL/OLO (where P is 16:0, palmitic
      acid; O is 18:1, oleic acid; and L is 18:2, linoleic acid). For the majority of
      [M + X](+) adducts, the loss of the fatty acid in the outer positions (sn-1 or sn
      3) was favored over the loss in the central position (sn-2), which enabled the
      determination of the fractional abundance of the isomers. Ratios of the intensity
      of fragment ions at various AAB/ABA compositions produced linear calibration
      curves with positive slopes, comparable to those obtained traditionally by ESI
      MS/MS of [M + NH(4)](+) adducts. The only exceptions were the [M + Ag](+) adducts
      of the PPO/POP system, which produced calibration curves with negative slopes.
      Sodium adducts provided the most consistent level of isomeric discrimination for
      the TAGs studied and also offered the most convenience in that they required no
      additive to the mobile phase. Therefore, calibration curve data derived from [M +
      Na](+) adducts were applied to the quantification of TAG regioisomers in
      sunflower and olive oils. The regiospecific analysis showed that palmitic acid
      was typically located at positions sn-1 or sn-3, whereas unsaturated fatty acids,
      oleic and linoleic acids were mostly found at the sn-2 position.

PMID- 20814980
TI  - Complex palytoxin-like profile of Ostreopsis ovata. Identification of four new
      ovatoxins by high-resolution liquid chromatography/mass spectrometry.
AB  - Over the past decades, Italian coastlines have been plagued by recurring presence
      of the benthic dinoflagellate Ostreopsis ovata. Such an alga has caused severe
      sanitary emergencies and economic losses due to its production of palytoxin-like
      compounds. Previous studies have confirmed the presence of ovatoxin-a (OVTX-a) as
      the major toxin of the algal toxin profile together with small amounts of
      putative palytoxin (PLTX). In our ongoing research on O. ovata toxins we report
      herein on in-depth investigation of an O. ovata culture carried out by high
      resolution (HR) liquid chromatography/mass spectrometry (LC/MS) and tandem mass
      spectrometry (MS(2)). Particularly, the presence of putative PLTX and OVTX-a was
      confirmed and the occurrence in the extract of four new palytoxin-like compounds,
      OVTX-b, -c, -d, and -e, was highlighted. Elemental formulae have been assigned to
      the new ovatoxins and information has been gained about their structural
      features. A quantitative study of the O. ovata culture extract indicated that the
      whole of the new ovatoxins represents about 46% of the total toxin content and,
      thus, their presence has to be taken into account when LC/MS-based monitoring
      programs of either plankton or contaminated seafood are carried out.

PMID- 20814982
TI  - Role of the UV absorber as a matrix in matrix-assisted laser
      desorption/ionization mass spectrometric analysis of a mixture of a UV absorber
      and a stabilizer.
AB  - A mixture of a UV absorber (Tinuvin 234 or Tinuvin 329) and a UV stabilizer
      (Tinuvin 770) was analyzed using matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS) without any matrix. Fragmentation patterns of the UV
      absorbers and stabilizer were also investigated. The mass spectra showed the
      [M+H](+) ions and some fragment ions. Tinuvin 234, Tinuvin 329, and Tinuvin 770
      generated three (m/z 119, 370, 432), one (m/z 252), and two (m/z 124 and 140)
      fragment ions, respectively. These fragment ions can be used to identify the
      chemical structures of the UV absorbers and stabilizer. Since the UV absorber
      performed a role as the matrix, the ion abundance of the UV stabilizer was
      enhanced by mixing with the UV absorber. When organic materials extracted from
      polypropylene (PP) containing the UV absorber and stabilizer were directly
      analyzed using MALDI-MS without any matrix, the protonated molecule of the UV
      stabilizer was detected in abundance but the product ions of the UV absorber were
      not observed. When 2,5-dihydroxybenzoic acid was used as a matrix, the protonated
      molecule of the UV absorber was observed.

PMID- 20814983
TI  - Online coupling of thin layer chromatography with matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry: synthesis and application
      of a new material for the identification of carbohydrates by thin layer
      chromatography/matrix free material enhanced laser desorption/ionization mass
      spectrometry.
AB  - This article describes the online hyphenation of thin layer chromatography with
      matrix free material enhanced laser desorption/ionization mass spectrometry (mf
      MELDI-MS), the preparation of new material for MELDI and application of this
      newly synthesized material using TLC/MELDI-MS for the analysis of carbohydrate
      reference standards and plant extracts. Samples included within these analyses
      are standard solutions of glucose, sucrose, raffinose and a plant extract of
      Quercus robur, which is used for its anti-inflammatory, anti-viral and
      anthelminitc properties in phytomedicine. A new material for mf-MELDI-MS is
      prepared by immobilizing bradykinin--a peptide, on silica gel coupled to 4-(3
      triethoxysilylpropylureido)azobenzene. This modification enables the absorption
      of laser energy sufficient for desorption and ionization of low molecular weight
      molecules like carbohydrates and amino acids. The newly synthesized material
      delivered excellent results in respect to signal-to-noise (S/N) ratio (S/N ratio:
      >9/1) and sensitivity (limit of detection (LOD): lower to ng/microL). Hyphenation
      of TLC to MELDI-MS employing the novel developed material simultaneously as
      chromatographic and mass spectrometric sorbent was shown for the first time for
      the analysis of low molecular weight molecules like mono- and oligosaccharides.

PMID- 20814984
TI  - Gas chromatography/time-of-flight mass spectrometry-based metabonomics of
      hepatocarcinoma in rats with lung metastasis: elucidation of the metabolic
      characteristics of hepatocarcinoma at formation and metastasis.
AB  - Hepatocarcinoma (HCC) has a very high mortality rate and the high recurrence and
      metastasis rates contribute to the poor prognosis of HCC patients. To understand
      HCC formation and metastasis, we assessed the metabonomics of rat HCC and HCC
      with lung metastasis (HLM). The HLM rat model was established by exposure to
      diethylnitrosamine (DEN). Levels of serum and urine metabolites were quantified
      with gas chromatography/time-of-flight mass spectrometry (GC/TOFMS), and data
      were analyzed with partial least-squares discrimination analysis (PLS-DA). Serum
      and urine levels of some metabolites differed significantly between the control,
      HCC, and HLM groups. The products and intermediates from glycolysis and glutamate
      metabolism were elevated, while the tricarboxylic acid (TCA) cycle was inhibited,
      in both HCC and HLM. HLM samples revealed enhanced metabolism of nucleic acids,
      amino acids and glucuronic acid. PLS-DA indicated that principal component
      weighting was greatest for serum serine, phenylalanine, lactic acid, tyrosine and
      glucuronic acid, and urine glycine, serine, 5-oxyproline, malate, hippuric acid
      and uric acid. These data provide novel information that will improve
      understanding of the pathophysiological processes involved in HCC and HLM, and
      revealed potential metabolic markers for HCC invasion and metastasis.

PMID- 20814985
TI  - Diastereomeric differentiation of two pairs of glycal derivatives by electrospray
      ionization tandem mass spectrometry.

PMID- 20814986
TI  - Investigation on fragmentation pathways of rutaecarpine and its two derivatives
      using electrospray ionization ion-trap time-of-flight tandem mass spectrometry.

PMID- 20814987
TI  - iTRAQ-coupled two-dimensional liquid chromatography/tandem mass spectrometric
      analysis of protein profile in Escherichia coli incubated with human neutrophil
      peptide 1--potential in antimicrobial strategy.

PMID- 20814988
TI  - Double disruption of alpha2A- and alpha2C-adrenoceptors results in sympathetic
      hyperactivity and high-bone-mass phenotype.
AB  - Evidence demonstrates that sympathetic nervous system (SNS) activation causes
      osteopenia via beta(2)-adrenoceptor (beta2-AR) signaling. Here we show that
      female mice with chronic sympathetic hyperactivity owing to double knockout of
      adrenoceptors that negatively regulate norepinephrine release, alpha(2A)-AR and
      alpha(2C)-AR (alpha(2A) /alpha(2C)-ARKO), present an unexpected and generalized
      phenotype of high bone mass with decreased bone resorption and increased
      formation. In alpha(2A) /alpha(2C)-ARKO versus wild-type (WT) mice, micro
      computed tomographic (uCT) analysis showed increased, better connected, and more
      plate-shaped trabeculae in the femur and vertebra and increased cortical
      thickness in the vertebra, whereas biomechanical analysis showed increased tibial
      and femoral strength. Tibial mRNA expression of tartrate-resistant acid
      phosphatase (TRACP) and receptor activator of NF-kappaB (RANK), which are
      osteoclast-related factors, was lower in knockout (KO) mice. Plasma leptin and
      brain mRNA levels of cocaine amphetamine-regulated transcript (CART), which are
      factors that centrally affect bone turnover, and serum levels of estradiol were
      similar between mice strains. Tibial beta(2)-AR mRNA expression also was similar
      in KO and WT littermates, whereas alpha(2A)-, alpha(2B)- and alpha(2C)-AR mRNAs
      were detected in the tibia of WT mice and in osteoblast-like MC3T3-E1 cells. By
      immunohistochemistry, we detected alpha(2A)-, alpha(2B)-, alpha(2C)- and beta(2)
      ARs in osteoblasts, osteoclasts, and chondrocytes of 18.5-day-old mouse fetuses
      and 35-day-old mice. Finally, we showed that isolated osteoclasts in culture are
      responsive to the selective alpha(2)-AR agonist clonidine and to the nonspecific
      alpha-AR antagonist phentolamine. These findings suggest that beta(2)-AR is not
      the single adrenoceptor involved in bone turnover regulation and show that
      alpha(2)-AR signaling also may mediate the SNS actions in the skeleton.

PMID- 20814990
TI  - Energy digestibility of giant pandas on bamboo-only and on supplemented diets.
AB  - Endangered giant pandas (Ailuropoda melanoleuca) are bears (Family Ursidae),
      within the order Carnivora. They specialize on an herbivorous diet of bamboo yet
      retain a gastrointestinal tract typical of their carnivorous ancestry. The
      evolutionary constraints of their digestive tract result in a low extraction
      efficiency from bamboo (<40% in reported studies). The goal of this study was to
      determine the energy digestibility of bamboo by giant pandas used in
      digestibility trials and through subsequent analyses with bomb calorimetry. Seven
      digestibility trials were conducted (three with bamboo-only diets and four with
      supplemental diets). Energy digestibilities ranged from 7.5-38.9% for mixed diets
      and 9.2-34.0% for bamboo-only diets. The bamboo-only trials summarized here
      represent, to our knowledge, the first empirical data available for energy
      digestibility on a bamboo diet for giant pandas.

PMID- 20814991
TI  - Modeling anhydrobiosis: activation of the mitogen-activated protein kinase ERK by
      dehydration in both human cells and nematodes.
AB  - Anhydrobiosis ("life without water") is the state of suspended animation that
      certain organisms, including some nematodes, tardigrades, and bdelloid rotifers,
      enter during desiccation. Extreme water loss imposes considerable stress on
      biomolecules, cells, and tissues, and must require specific sensing and response
      mechanisms for survival. However, these mechanisms are poorly understood, in part
      owing to the lack of amenable model systems. We have, therefore, begun to develop
      mammalian cell lines as tools for investigating the eukaryotic response to
      desiccation, and have an additional long-term goal of generating a desiccation
      tolerant mammalian cell. Here, we investigate the role of the mitogen-activated
      protein kinases (MAPKs) in controlling gene expression in response to evaporative
      water loss. We report that the ERK MAPK pathway inhibitor U0126 can almost
      completely block induction of desiccation early response genes in a human cell
      line, suggesting a role for the ERK signal transduction pathway in the stress
      response. Accordingly, ERK is activated by phosphorylation during desiccation of
      human cells. Importantly, nematodes also activate ERK on drying, showing that the
      mammalian cell model behaves similarly to invertebrates experiencing similar
      stress conditions. We further reveal that, in response to desiccation, human
      cells can rapidly initiate complex stress signaling networks involving all three
      MAPK pathways, with transient activation of ERK and sustained activation of JNK
      and p38. These results are consistent with a role for MAPK pathways in
      anhydrobiotic adaptation and suggest that non-anhydrobiotes are able to sense
      and, at least to some extent, respond appropriately to evaporative water loss.

PMID- 20814992
TI  - A fluorescent rosamine compound selectively stains pluripotent stem cells.

PMID- 20814993
TI  - The bicorannulenyl dianion: a charged overcrowded ethylene.

PMID- 20814994
TI  - Pharmaceutical nano-cocrystals: sonochemical synthesis by solvent selection and
      use of a surfactant.

PMID- 20814995
TI  - An octanuclear [Cr(III)4Dy(III)4] 3d-4f single-molecule magnet.

PMID- 20814996
TI  - Surface-tension-induced synthesis of complex particles using confined polymeric
      fluids.

PMID- 20814998
TI  - Fluorous biphase synthesis of a poly(p-phenyleneethynylene) and its fluorescent
      aqueous fluorous-phase emulsion.

PMID- 20814997
TI  - Selective modulation of DNA polymerase activity by fixed-conformation nucleoside
      analogues.

PMID- 20814999
TI  - Entropy-controlled catalytic asymmetric 1,4-type Friedel-Crafts reaction of
      phenols using conformationally flexible guanidine/bisthiourea organocatalyst.

PMID- 20815000
TI  - Azidohomoalanine: a conformationally sensitive IR probe of protein folding,
      protein structure, and electrostatics.

PMID- 20815001
TI  - Efficient organic-dye-sensitized solar cells based on an iodine-free electrolyte.

PMID- 20815002
TI  - Total chemical synthesis of di-ubiquitin chains.

PMID- 20815003
TI  - Competition between orbitals and stress in mechanochemistry.

PMID- 20815004
TI  - Dichlorocyclodibismadiazane.

PMID- 20815005
TI  - [Fe]-hydrogenase models featuring acylmethylpyridinyl ligands.

PMID- 20815006
TI  - Proteomic analysis of the acid-soluble nacre matrix of the bivalve Unio pictorum:
      detection of novel carbonic anhydrase and putative protease inhibitor proteins.
AB  - The matrix extracted from mollusc shell nacre is a mixture of proteins and
      glycoproteins that is thought to play a major role in controlling biomineral
      synthesis and in increasing its mechanical properties. We investigated the
      nacreous shell of the freshwater mussel Unio pictorum, to which we applied a
      proteomics approach adapted to mollusc shell proteins. On one hand, the acid
      soluble nacre matrix was fractionated by SDS-PAGE and the five main protein bands
      (P95, P50, P29, P16, and P12) were digested with trypsin and analyzed by nanoLC
      MS/MS followed by de novo sequencing. On the other hand, the acid-soluble nacre
      matrix was analyzed in a similar manner, without any preliminary fractionation.
      In total, we obtained about 140 peptides, of between 9 and 21 residues, as well
      as several shorter peptides. Interestingly, it appears that the different protein
      bands share several identical peptides; this has implications for the underlying
      genetic machinery that synthesizes nacre proteins. Homology searches against
      sequences in the Swiss-Prot protein database and the 800,000 mollusc expressed
      sequence tag database were performed, but surprisingly, only a few obvious
      homologies were established. Among the peptides that match with known sequences,
      some from P50 and P16/P12 proteins align with carbonic anhydrase (CA) and with
      the protease inhibitor, respectively. The evolutionary implications of our
      findings are discussed.

PMID- 20815007
TI  - The influence of surface composition of nanoparticles on their interactions with
      serum albumin.
AB  - Interactions between differently functionalised silver and gold nanoparticles
      (NPs) as well as polystyrene nanoparticles with bovine serum albumin (BSA) are
      studied using circular dichroism (CD) spectroscopy. It is found that the addition
      of NPs to the protein solution destroys part of the helical secondary structure
      of the protein as a result of surface adsorption. From the loss of free protein
      and hence the extent of their structural change adsorption equilibrium constants
      are derived. The results reveal that citrate-coated gold and silver NPs exhibit
      much stronger interactions with BSA than polymeric or polymer-coated metallic
      NPs. It is therefore concluded that for the particles considered, the influence
      of surface composition on the interaction behaviour dominates that of the core.

PMID- 20815008
TI  - Unimolecular reactions of peroxy radicals in atmospheric chemistry and
      combustion.
AB  - Peroxy radicals can undergo isomerisation and dissociation reactions in
      competition with reactions with NO and with other peroxy radicals. Such a
      competition is central to the recently proposed mechanism for OH regeneration in
      the atmospheric oxidation of isoprene. The occurrence of peroxy radical
      isomerisation reactions in both combustion and atmospheric chemistry is
      discussed, and exemplified by reference to the peroxy radicals formed from the
      C(2)H(5), CH(3)CO, HO-C(2)H(2) and HO-C(6)H(6) radicals. The discussion is based
      on the use of electronic structure and master equation calculations to interpret
      experimental results.

PMID- 20815009
TI  - Conformational properties of arenicins: from the bulk to the air-water interface.
AB  - The structures of two antimicrobial peptides (arenicin Ar-1 and its linear
      derivative C/S-Ar-1) are studied in different solutions and at the air-water
      interface using spectroscopic methods such as circular dichroism (CD) and
      infrared reflection absorption spectroscopy (IRRAS) as well as grazing incidence
      X-ray diffraction (GIXD) and specular X-ray reflectivity (XR). Both peptides
      exhibit similar structures in solution. In the buffer used for most of the
      experiments the main secondary structure elements are 22 % beta-turn, 38 % beta
      sheet and 38 % random coil. The amphiphilic peptides are surface-active and form
      a Gibbs monolayer at the air-buffer interface. The surface activity is
      drastically increased by increasing the ionic strength of the subphase. The beta
      sheet layer is quite stable and can be compressed to higher surface pressures.
      This adsorption layer is very crystalline. Bragg peaks corresponding to an
      interstrand distance of 4.78 A and to an end-to-end distance have been observed.
      This end-to-end distance can be connected with the observed differences in the
      layer thickness leading to the assumption that the peptides form a hairpin which
      is bended depending on the interactions with the counterions.

PMID- 20815010
TI  - A universal ultracentrifuge spectrometer visualizes CNT-intercalant-surfactant
      complexes.

PMID- 20815011
TI  - Design and synthesis of selective and potent orally active S1P5 agonists.

PMID- 20815012
TI  - Understanding the key factors that control the inhibition of type II
      dehydroquinase by (2R)-2-benzyl-3-dehydroquinic acids.
AB  - The binding mode of several substrate analogues, (2R)-2-benzyl-3-dehydroquinic
      acids 4, which are potent reversible competitive inhibitors of type II
      dehydroquinase (DHQ2), the third enzyme of the shikimic acid pathway, has been
      investigated by structural and computational studies. The crystal structures of
      Mycobacterium tuberculosis and Helicobacter pylori DHQ2 in complex with one of
      the most potent inhibitor, p-methoxybenzyl derivative 4 a, have been solved at
      2.40 A and 2.75 A, respectively. This has allowed the resolution of the M.
      tuberculosis DHQ2 loop containing residues 20-25 for the first time. These
      structures show the key interactions of the aromatic ring in the active site of
      both enzymes and additionally reveal an important change in the conformation and
      flexibility of the loop that closes over substrate binding. The loop conformation
      and the binding mode of compounds 4 b-d has been also studied by molecular
      dynamics simulations, which suggest that the benzyl group of inhibitors 4 prevent
      appropriate orientation of the catalytic tyrosine of the loop for proton
      abstraction and disrupts its basicity.

PMID- 20815013
TI  - How many species of woolly monkeys inhabit Colombian forests?
AB  - There is a controversy regarding how many species the genus Lagothrix contains,
      since the Lagothrix lagothricha subspecies have been recently proposed to be
      actual species. Clarification of species status is of particular importance in
      the case of L. l. lugens, because it is the most endangered and its distribution
      is restricted to the Colombian Andes, a highly deforested region. Using
      cytogenetic and molecular markers, we obtained evidence indicating that the
      subspecies status is appropriate for the two taxa occurring in this country. We
      also report high levels of intraspecific variability in the karyotype. We find
      evidence for a late Pleistocene separation of the subspecies, and we propose it
      is the limited area of contact between the taxa that allowed for them to
      partially differentiate.

PMID- 20815014
TI  - Hepatitis C treatment in an urban population.

PMID- 20815016
TI  - Does cardiac dysfunction explain deleterious effects of beta-blockers in
      cirrhosis and refractory ascites?

PMID- 20815017
TI  - Phosphoinositide 3-kinase/protein kinase B signaling pathway is involved in
      estradiol 17beta-D-glucuronide-induced cholestasis: complementarity with
      classical protein kinase C.
AB  - Estradiol 17beta-D-glucuronide (E(2)17G) is an endogenous, cholestatic metabolite
      that induces endocytic internalization of the canalicular transporters relevant
      to bile secretion: bile salt export pump (Bsep) and multidrug resistance
      associated protein 2 (Mrp2). We assessed whether phosphoinositide 3-kinase (PI3K)
      is involved in E(2)17G-induced cholestasis. E(2)17G activated PI3K according to
      an assessment of the phosphorylation of the final PI3K effector, protein kinase B
      (Akt). When the PI3K inhibitor wortmannin (WM) was preadministered to isolated
      rat hepatocyte couplets (IRHCs), it partially prevented the reduction induced by
      E(2)17G in the proportion of IRHCs secreting fluorescent Bsep and Mrp2 substrates
      (cholyl lysyl fluorescein and glutathione methylfluorescein, respectively). 2
      Morpholin-4-yl-8-phenylchromen-4-one, another PI3K inhibitor, and an Akt
      inhibitor (Calbiochem 124005) showed similar protective effects. IRHC
      immunostaining and confocal microscopy analysis revealed that endocytic
      internalization of Bsep and Mrp2 induced by E(2)17G was extensively prevented by
      WM; this effect was fully blocked by the microtubule-disrupting agent colchicine.
      The protection of WM was additive to that afforded by the classical protein
      kinase C (cPKC) inhibitor 5,6,7,13-tetrahydro-13-methyl-5-oxo-12H-indolo[2,3
      a]pyrrolo[3,4-c]carbazole-12-propanenitrile (Go6976); this suggested differential
      and complementary involvement of the PI3K and cPKC signaling pathways in E(2)17G
      induced cholestasis. In isolated perfused rat liver, an intraportal injection of
      E(2)17G triggered endocytosis of Bsep and Mrp2, and this was accompanied by a
      sustained decrease in the bile flow and the biliary excretion of the Bsep and
      Mrp2 substrates [(3)H]taurocholate and glutathione until the end of the perfusion
      period. Unlike Go6976, WM did not prevent the initial decay, but it greatly
      accelerated the recovery to normality of these parameters and the reinsertion of
      Bsep and Mrp2 into the canalicular membrane in a microtubule-dependent manner.
      CONCLUSION: The PI3K/Akt signaling pathway is involved in the biliary secretory
      failure induced by E(2)17G through sustained internalization of canalicular
      transporters endocytosed via cPKC.

PMID- 20815018
TI  - Treatment response in patients with autoimmune hepatitis.

PMID- 20815019
TI  - Activation of LKB1-Akt pathway independent of phosphoinositide 3-kinase plays a
      critical role in the proliferation of hepatocellular carcinoma from nonalcoholic
      steatohepatitis.
AB  - LKB1, originally considered a tumor suppressor, plays an important role in
      hepatocyte proliferation and liver regeneration. Mice lacking the methionine
      adenosyltransferase (MAT) gene MAT1A exhibit a chronic reduction in hepatic S
      adenosylmethionine (SAMe) levels, basal activation of LKB1, and spontaneous
      development of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma
      (HCC). These results are relevant for human health because patients with liver
      cirrhosis, who are at risk to develop HCC, have a marked reduction in hepatic
      MAT1A expression and SAMe synthesis. In this study, we isolated a cell line (SAMe
      deficient [SAMe-D]) from MAT1A knockout (MAT1A-KO) mouse HCC to examine the role
      of LKB1 in the development of liver tumors derived from metabolic disorders. We
      found that LKB1 is required for cell survival in SAMe-D cells. LKB1 regulates Akt
      mediated survival independent of phosphoinositide 3-kinase, adenosine
      monophosphate protein-activated kinase (AMPK), and mammalian target of rapamycin
      complex (mTORC2). In addition, LKB1 controls the apoptotic response through
      phosphorylation and retention of p53 in the cytoplasm and the regulation of
      herpesvirus-associated ubiquitin-specific protease (HAUSP) and Hu antigen R (HuR)
      nucleocytoplasmic shuttling. We identified HAUSP as a target of HuR. Finally, we
      observed cytoplasmic staining of p53 and p-LKB1(Ser428) in a NASH-HCC animal
      model (from MAT1A-KO mice) and in liver biopsies obtained from human HCC derived
      from both alcoholic steatohepatitis and NASH. CONCLUSION: The SAMe-D cell line is
      a relevant model of HCC derived from NASH disease in which LKB1 is the principal
      conductor of a new regulatory mechanism and could be a practical tool for
      uncovering new therapeutic strategies.

PMID- 20815020
TI  - Programmed death-1/B7-H1 negative costimulation protects mouse liver against
      ischemia and reperfusion injury.
AB  - Programmed death-1 (PD-1)/B7-H1 costimulation acts as a negative regulator of
      host alloimmune responses. Although CD4 T cells mediate innate immunity-dominated
      ischemia and reperfusion injury (IRI) in the liver, the underlying mechanisms
      remain to be elucidated. This study focused on the role of PD-1/B7-H1 negative
      signaling in liver IRI. We used an established mouse model of partial liver warm
      ischemia (90 minutes) followed by reperfusion (6 hours). Although disruption of
      PD-1 signaling after anti-B7-H1 monoclonal antibody treatment augmented
      hepatocellular damage, its stimulation following B7-H1 immunoglobulin (B7-H1Ig)
      fusion protected livers from IRI, as evidenced by low serum alanine
      aminotransferase levels and well-preserved liver architecture. The therapeutic
      potential of B7-H1 engagement was evident by diminished intrahepatic T
      lymphocyte, neutrophil, and macrophage infiltration/activation; reduced cell
      necrosis/apoptosis but enhanced anti-necrotic/apoptotic Bcl-2/Bcl-xl; and
      decreased proinflammatory chemokine/cytokine gene expression in parallel with
      selectively increased interleukin (IL)-10. Neutralization of IL-10 re-created
      liver IRI and rendered B7-H1Ig-treated hosts susceptible to IRI. These findings
      were confirmed in T cell-macrophage in vitro coculture in which B7-H1Ig
      diminished tumor necrosis factor-alpha/IL-6 levels in an IL-10-dependent manner.
      Our novel findings document the essential role of the PD-1/B7-H1 pathway in liver
      IRI. CONCLUSION: This study is the first to demonstrate that stimulating PD-1
      signals ameliorated liver IRI by inhibiting T cell activation and Kupffer
      cell/macrophage function. Harnessing mechanisms of negative costimulation by PD-1
      upon T cell-Kupffer cell cross-talk may be instrumental in the maintenance of
      hepatic homeostasis by minimizing organ damage and promoting IL-10-dependent
      cytoprotection.

PMID- 20815021
TI  - Use of sirolimus in liver transplant recipients with renal insufficiency: a
      systematic review and meta-analysis.
AB  - Sirolimus is used in patients with renal insufficiency after liver
      transplantation (LT) and especially in those with calcineurin inhibitor (CNI)
      associated nephrotoxicity. We conducted a systematic review of all randomized
      controlled trials and observational studies to test the hypothesis that the use
      of sirolimus is associated with an improvement in renal function at 1 year in LT
      recipients with renal insufficiency [glomerular filtration rate (GFR) < 60
      mL/minute or creatinine level >= 1.5 mg/dL]. We performed a search of all major
      databases, conference proceedings, and relevant journals through December 2009
      and contacted content experts, corresponding authors, and the pharmaceutical
      manufacturer. A random effects model was used to determine the pooled estimate of
      the change in renal function and pooled risk estimates of adverse events that may
      be associated with sirolimus-based therapy at 1 year. Eleven studies (three
      randomized controlled trials and eight observational studies) met the final
      inclusion criteria. A nonsignificant improvement of 3.38 mL/minute [95%
      confidence interval (CI) = -2.93 to 9.69] was observed in methodologically sound
      observational studies and controlled trials reporting the primary outcome. In
      controlled trials, baseline GFR >50 mL/min sirolimus use was associated with an
      improvement of 10.35 mL/minute (95% CI = 3.98-16.77) in GFR or creatinine
      clearance. Sirolimus was not significantly associated with death [relative risk
      (RR) = 1.12, 95% CI = 0.66-1.88] or graft failure (RR = 0.80, 95% CI = 0.45
      1.41), although reporting was incomplete. It was associated with a statistically
      significant risk of infection (RR = 2.47, 95% CI = 1.14-5.36), rash (RR = 7.57,
      95% CI = 1.75-32.70), ulcers (RR = 7.44, 95% CI = 2.03-27.28), and
      discontinuation of therapy (RR = 3.61, 95% CI = 1.32-9.89). CONCLUSION:
      Conversion to sirolimus from CNIs is associated with a nonsignificant improvement
      in renal function in LT recipients with renal insufficiency, although the results
      are limited by heterogeneity, a risk of bias, and a lack of standardized
      reporting.

PMID- 20815022
TI  - Cellular phone-based photoplethysmographic imaging.
AB  - We present study results on visible light reflection photoplethysmographic (PPG)
      imaging with a mobile cellular phone operated in video imaging mode. PPG signal
      components around 0.1 Hz attributed to the sympathetic component of the heart
      rate, 1 Hz as the heart rate and 2 Hz as heart rate high order harmonic were
      quantified on the index finger of a healthy volunteer. The green channel reported
      PPG signals throughout the sampled area. The blue and red channel returned
      plethysmographic information, but the signal strength was highly position
      specific. Our results obtained with a cellular phone as the data acquisition
      device are encouraging, especially in the broad context of personal or home-based
      care and the role of cellular phone technology in medical imaging.

PMID- 20815023
TI  - Effect of SDS on human hair: Study on the molecular structure and morphology.
AB  - This paper presents a model study to understand the effect of surfactants on the
      physicochemical properties of human hair. FT-IR ATR spectroscopy has been
      employed to understand the chemical changes induced by sodium dodecyl sulfate
      (SDS) on human scalp hair. In particular, the SDS induced changes in the
      secondary structure of protein present in the outer protective layer of hair,
      i.e. cuticle, have been investigated. Conformational changes in the secondary
      structure of protein were studied by curve fitting of the amide I band after
      every phase of SDS treatment. It has been found that SDS brings rearrangements in
      the protein backbone conformations by transforming beta -sheet structure to
      random coil and beta -turn. Additionally, AFM and SEM studies were carried out to
      understand the morphological changes induced on the hair surface. SEM and AFM
      images demonstrated the rupture and partial erosion of cuticle sublayers.

PMID- 20815024
TI  - Second-harmonic generation voltage imaging at subcellular resolution in rat
      hippocampal slices.
AB  - Action potential (AP) is a major signaling mechanism in the neuronal networks.
      Dendritic AP propagation is important for information processing within the
      individual neurons. Due to limitations of electrode-based techniques most
      research on subcellular AP propagation has been restricted to soma and proximal
      parts of the primary dendrites. Development of voltage-sensitive dyes (VSD) has
      opened up a possibility to measure voltage changes in the oblique dendrites and
      the spines. Membrane-bound organic VSD can be used both for fluorescent imaging
      and imaging of second-harmonic generation (SHG). Both phenomena are voltage
      dependent and can be used for measuring membrane potential changes. However,
      changes in SHG are linear to the change in the local membrane potential and its
      slope is constant across different compartments of cells. Although SHG
      demonstrates reasonable change with membrane voltage (over 10% per 100 mV), the
      signal-to-noise (S/N) ratio is currently lower in SHG measurement than in
      fluorescent methods.

PMID- 20815025
TI  - Impact of hepatitis B virus surface protein mutations on the diagnosis of occult
      hepatitis B virus infection.
AB  - Genotype D occult hepatitis B virus (HBV) infections (OBIs) have a high frequency
      of amino acid substitutions in the major hydrophilic region of the small surface
      protein (S protein). This possibly reflects an escape mutation mechanism to evade
      detection by the host immune system. Mutations may also impact the detection of
      hepatitis B surface antigen (HBsAg) by commercial assays. To test these
      hypotheses, 20 recombinant HBV genotype D surface proteins from OBI carriers with
      or without antibody to hepatitis B surface antigen (anti-HBs) were expressed in
      yeast. Recombinant surface protein (rS protein) variants were nonreactive with
      autologous anti-HBs but reacted weakly with vaccine-induced anti-HBs supporting
      an immune escape mechanism. rS protein variants tested with a wide range of HBs
      antibodies, and HBsAg commercial assays showed significantly lower antigenic
      reactivity in anti-HBs carriers than in donors with antibody to hepatitis B core
      antigen (anti-HBc) only. Eight out of 10 recombinant variants from anti-HBs
      carriers reacted weakly or were nonreactive with antibodies to HBs as well as
      with qualitative and quantitative commercial HBsAg assays, whereas eight out of
      10 anti-HBc-only plasmas were fully reactive. rS proteins with substitutions of
      wild-type cysteine at positions 121, 124, and 137 were nonreactive or showed poor
      reactivity. However, mutation of cysteine 147 did not alter reactivity compared
      with controls. Restoration of cysteines 124 and 137 by site-directed mutagenesis
      improved antigenic reactivity. CONCLUSION: Escape mutation is a mechanism
      associated with OBI, which also leads to decreased reactivity in HBsAg detection
      assays. Performance of commercial assays would be improved by the incorporation
      of OBI mutants in reagent development.

PMID- 20815027
TI  - Memorial: Roy Reed Peterson (1924 -2010), Emeritus Professor of Anatomy at
      Washington University School of Medicine.

PMID- 20815028
TI  - Mullerian cyst of the mesentery: A case report of an unusual location.
AB  - Mullerian cysts or paramesonephric cysts arise from the fused embryonic ducts,
      which typically regress in the uterus. These cysts are usually located
      paravertebrally. We present an unusual case of a Mullerian cyst developing within
      the mesentery of the ileocecum that was successfully resected. The patient
      presented to our surgical unit with abdominal pain and swelling. She underwent
      all the necessary tests to rule out other pathologies before she underwent right
      hemicolectomy. The patient was discharged without complications. Histopathology
      confirmed the presence of female reproductive tract epithelium, which was
      conclusive of a Mullerian cyst or paramesonephric cyst. Mullerian cysts are
      rarely malignant, and they are usually treated surgically. The incidence of
      Mullerian cysts is one in 105,000, with almost equal sex distribution. Their
      unusual intraperitoneal location further demonstrates their uncommon
      presentation.

PMID- 20815029
TI  - Familial concordance of breast cancer pathology as an indicator of genotype in
      multiple-case families.
AB  - The heterogeneity of multiple case breast cancer families that do not carry
      mutations in BRCA1 or BRCA2 (non-BRCA1/2 families) poses a challenge to the
      identification of breast cancer susceptibility genes. The aim of this study was
      to determine whether intrafamilial concordance in breast cancer pathology could
      identify subgroups of non-BRCA1/2 families with consistent genotypic features.
      Invasive breast cancers were reviewed from 84 individuals belonging to 30
      multiple-case families; BRCA1 (n = 9), BRCA2 (n = 10), and non-BRCA1/2 (n = 11).
      Hierarchical cluster analysis based on histopathology and age at first diagnosis
      was then used to specify three subgroups designated Clusters 1-3. The genomic
      features of non-BRCA1/2 families were examined by genome wide linkage and FGFR2
      SNP genotyping, according to whether they showed cluster-concordant or cluster
      mixed familial pathology. The majority of pathogenic BRCA1 mutation carriers
      (80%) fell into a single cluster. In contrast pathogenic BRCA2 mutation carriers
      were distributed across all three clusters and within families, cluster groups
      were also generally mixed. Most non-BRCA1/2 mutation carriers belonged to Cluster
      3 (71%). Genome wide linkage data from five non-BRCA1/2 Cluster 3-concordant
      families were compared with four mixed cluster non-BRCA1/2 families. This
      revealed a number of distinct linkage peaks, including some regions previously
      associated with breast cancer susceptibility. The distribution of low risk
      alleles in FGFR2 was not different between these two subgroups (P = 0.237). The
      pattern of breast cancer pathology concordance amongst family members may assist
      the investigation of breast cancer susceptibility in multiple case families.

PMID- 20815030
TI  - Evaluation of multiplex ligation-dependent probe amplification as a method for
      the detection of copy number abnormalities in B-cell precursor acute
      lymphoblastic leukemia.
AB  - Recent genomic studies have shown that copy number abnormalities (CNA) of genes
      involved in lymphoid differentiation and cell cycle control are common in B-cell
      precursor acute lymphoblastic leukemia (BCP-ALL). We have evaluated Multiplex
      Ligation-dependent Probe Amplification (MLPA) on 43 BCP-ALL patients for the
      detection of the most common deletions among these genes and compared the results
      to those obtained by fluorescence in situ hybridization (FISH) and genomic
      quantitative PCR (qPCR). There was good correlation between methods for CDKN2A/B,
      IKZF1, and PAX5 deletions in the majority of cases and MLPA confirmed the
      presence of deletions within the PAR1 region in two of three cases identified by
      FISH. Small intragenic aberrations detected by MLPA, which were below the
      resolution of FISH for CDKN2A/B (n = 7), IKZF1 (n = 3), and PAX5 (n = 3) were
      confirmed by qPCR. MLPA and qPCR were unable to detect populations present at a
      low level (<20%) by FISH. In addition, although MLPA identified the presence of a
      deletion, it was unable to discern the presence of mixed cell populations which
      had been identified by FISH: CDKN2A/B (n = 3), IKZF1 (n = 1), PAX5 (n = 2), and
      PAR1 deletion (n = 1). Nevertheless, this study has demonstrated that MLPA is a
      robust technique for the reliable detection of CNA involving multiple targets in
      a single test and thus is ideal for rapid high throughput testing of large
      cohorts with a view to establishing incidence and prognostic significance.

PMID- 20815031
TI  - A novel mutation in the fatty acid transport protein 4 gene in a patient
      initially described as affected by self-healing congenital verruciform
      hyperkeratosis.

PMID- 20815032
TI  - EWSR1-POU5F1 fusion in soft tissue myoepithelial tumors. A molecular analysis of
      sixty-six cases, including soft tissue, bone, and visceral lesions, showing
      common involvement of the EWSR1 gene.
AB  - The diagnosis of myoepithelial (ME) tumors outside salivary glands remains
      challenging, especially in unusual clinical presentations, such as bone or
      visceral locations. A few reports have indicated EWSR1 gene rearrangement in soft
      tissue ME tumors, and, in one case each, the fusion partner was identified as
      either PBX1 or ZNF444. However, larger studies to investigate whether these
      genetic abnormalities are recurrent or restricted to tumors in soft tissue
      locations are lacking. Sixty-six ME tumors mainly from soft tissue (71%), but
      also from skin, bone, and visceral locations, characterized by classic
      morphological features and supporting immunoprofile were studied. Gene
      rearrangements in EWSR1, FUS, PBX1, and ZNF444 were investigated by fluorescence
      in situ hybridization. EWSR1 gene rearrangement was detected in 45% of the cases.
      A EWSR1-POU5F1 fusion was identified in a pediatric soft tissue tumor by 3'Rapid
      Amplification of cDNA Euds (RACE) and subsequently confirmed in four additional
      soft tissue tumors in children and young adults. An EWSR1-PBX1 fusion was seen in
      five cases, whereas EWSR1-ZNF444 and FUS gene rearrangement was noted in one
      pulmonary tumor each. In conclusion, EWSR1 gene rearrangement is a common event
      in ME tumors arising outside salivary glands, irrespective of anatomical
      location. EWSR1-negative tumors were more often benign, superficially located,
      and showed ductal differentiation, suggesting the possibility of genetically
      distinct groups. A subset of soft tissue ME tumors with clear cell morphology
      harbor an EWSR1-POU5F1 fusion, which can be used as a molecular diagnostic test
      in difficult cases. These findings do not support a pathogenetic relationship
      between soft tissue ME tumors and their salivary gland counterparts.

PMID- 20815033
TI  - R75Q dominant mutation in GJB2 gene silenced by the in Cis recessive mutation
      c.35delG.

PMID- 20815034
TI  - Examining the evidence for vascular pathogenesis of selected birth defects.
AB  - Vascular mechanisms have been proposed to be involved in the pathogenesis of a
      number of defects, including transverse-limb defects, intestinal atresias,
      gastroschisis, hydranencephaly, porencephaly, oromandibular-limb hypogenesis
      sequence, and oculoauriculovertebral spectrum (OAVS). Here, we examine the
      available clinical, epidemiologic, and experimental evidence for four defects
      (transverse-limb defects, intestinal atresias, gastroschisis, and OAVS) for which
      vascular pathogenesis has been hypothesized. Based on our review, transverse-limb
      defects appear to sometimes be due to vascular events related to placental
      vascular abnormalities, hypoperfusion, abnormal development of blood vessels,
      intrauterine compression, hemoglobinopathies, or exposure to vasoactive agents,
      although epidemiological studies have not consistently demonstrated the latter
      association. However, transverse-limb defects can also be due to abnormal
      developmental events, such as aberrant molecular signaling in the apical
      ectodermal ridge. Some intestinal atresias may have a vascular origin, with the
      hypothesis supported by experiments in canines. However, evidence is accumulating
      that a more common mechanism might be related to improper molecular signaling
      related to gut specification early in development. In contrast, evidence to
      support vascular pathogenesis for gastroschisis and OAVS is less compelling.
      Instead, these defects probably arise from interference with basic developmental
      events [e.g., body wall closure (gastroschisis) and neural crest cell development
      (OAVS)]. These conclusions are important for counseling parents of children with
      these defects and for guiding the design of future epidemiological studies and
      experiments to further characterize the causes of these defects.

PMID- 20815035
TI  - Mucinous cystadenoma of ovary in a patient with juvenile polyposis due to 10q23
      microdeletion: expansion of phenotype.
AB  - Juvenile polyposis syndrome (JPS) is a hereditary condition characterized by
      development of gastrointestinal polyps, and caused by mutations in SMAD4 or
      BMPR1A genes. Juvenile polyps can also be found in a related group of syndromes
      with multisystemic involvement including Cowden disease, Lhermitte-Duclos
      disease, Bannayan-Riley-Ruvalcaba syndrome, and Proteus-like syndrome, all
      grouped as PTEN hamartoma tumor syndromes (PHTS). In all these conditions
      including JPS, polyps manifest in older childhood or early adulthood. Infantile
      juvenile polyposis (JPI) is a rare entity, presenting in the first year of life
      with severe gastrointestinal symptoms. Many of these patients have associated
      macrocephaly, hypotonia, and congenital anomalies. It was recently recognized
      that patients with infantile polyposis have a 10q23 microdeletion, involving both
      BMPR1A and PTEN genes. There is a major risk for gastrointestinal malignancies in
      these patients, but the risk for development of other tumors is not known. We
      describe a patient with a history of infantile polyposis, macrocephaly,
      developmental delay, hypotonia, and a 10q23 microdeletion. At age 14 she
      presented with bilateral mucinous cystadenoma of the ovary. This type of tumor
      was not previously reported in association with JPS, 10q23 microdeletion
      syndrome, or infantile polyposis. We believe that ovarian cystadenomas may be
      another neoplastic complication of infantile polyposis, and that our report
      widens the spectrum of the 10q23 microdeletion phenotype.

PMID- 20815036
TI  - Atypical presentations and specific genotypes are associated with a delay in
      diagnosis in females with Rett syndrome.
AB  - There is often delay between onset of Rett syndrome symptoms and its diagnosis,
      possibly related to symptom presentation or socio-demographic factors. We
      hypothesized that girls with an atypical presentation or whose family had a lower
      socio-economic status would receive a later diagnosis. Female subjects with a
      confirmed diagnosis of Rett syndrome were sourced from the Australian Rett
      Syndrome and InterRett Databases. Variables analyzed included timing and
      development of symptoms; MECP2 mutation type; parental occupation and education;
      maternal age and birth order. Residential location and socio-economic status were
      also analyzed for the Australian cases. Linear regression was used to determine
      relationships between these factors and age at diagnosis. A total of 909 cases
      were included. An older age of diagnosis was associated with later loss of hand
      function and speech, later onset of hand stereotypies and the presence of the
      p.R133C or p.R294X MECP2 mutation. Socio-economic factors did not predict age of
      diagnosis for Australian families. For families participating in the InterRett
      database, a younger age of diagnosis was associated with higher levels of
      parental education or occupation. A clinical picture consistent with the classic
      presentation of Rett syndrome is associated with an earlier diagnosis. Clinicians
      need to be alerted to the variable presentation of Rett syndrome including the
      milder phenotypes of cases with the p.R133C or p.R294X mutation. Educational
      resources to assist this understanding including guidance on when to request
      genetic testing could be useful to streamline the process of diagnosis in Rett
      syndrome.

PMID- 20815037
TI  - Immunohistochemical study of vesicle monoamine transporter 2 in the hippocampal
      region of genetic animal model of schizophrenia.
AB  - Recent research in the etiology of schizophrenia revealed that there may be some
      neurodevelopmental failures such as neuronal network incompetence in the brain of
      this disease, and neurotransmitters cannot function accurately or adequately.
      But, it is unknown precisely what kinds of deficit in neurotransmission may be
      existed histopathologically. We investigated the expression of vesicle monoamine
      transporter 2 (VMAT2), which has a significant role in neurotransmission, in the
      hippocampal formation of the animal model of schizophrenia, 14-3-3 epsilon hetero
      knockout (KO) mouse, using an immunohistochemical staining technique to clarify
      the neuronal abnormalities in the model animal. As a result, the expression of
      VMAT2 was increased significantly in the hippocampal formation of 14-3-3 epsilon
      hetero KO mice compared to that of the wild-type littermates. In conclusion,
      these findings might be related the pathophysiology of this disease includes a
      monoaminergic transmission abnormality, based on the investigation in a
      genetically-modified mouse as schizophrenic model.

PMID- 20815038
TI  - Detection of Mycobacterium avium subsp. paratuberculosis (MAP)-specific IS900 DNA
      and antibodies against MAP peptides and lysate in the blood of Crohn's disease
      patients.

PMID- 20815039
TI  - Development of a fast LC-MS/MS method for quantification of rilmenidine in human
      serum: elucidation of fragmentation pathways by HRMS.
AB  - Rilmenidine is an alpha 2 adrenoreceptor agonist used in the treatment of mild
      and moderate hypertension. In this study, a fast and accurate liquid
      chromatographic method with tandem mass spectrometric detection has been
      validated in order to assure quantification of rilmenidine in human serum. The
      fragmentation pathway of protonated rilmenidine was studied using high-resolution
      mass spectrometry (HRMS). This study compared selectivity, linearity, accuracy,
      precision, extraction efficiency, matrix effect and sensitivity using common
      liquid-liquid extraction (LLE) and solid-phase extraction (SPE) procedures. The
      limit of quantitation for both extraction techniques was 0.1 ng/ml. Several
      differences between the LLE and SPE have been observed in terms of linearity,
      accuracy, precision and matrix effect. Additionally, the advantages of SPE
      included less manual work load and increased recovery of rilmenidine in human
      serum to approximately 80% (LLE, 57%). The developed method involving SPE was
      found to be accurate (relative error (RE) < 5%), reproducible (relative standard
      deviation, RSD < 7%), robust and suitable for quantitative analysis of
      rilmenidine in serum samples obtained from patients under antihypertensive
      treatment.

PMID- 20815040
TI  - Conformational and thermal properties of phaseolin, the major storage protein of
      red kidney bean (Phaseolus vulgaris L.).
AB  - BACKGROUND: A previous study of various functional and physicochemical properties
      of phaseolin indicated good potential of phaseolin for application in food
      formulations in view of its excellent functional properties. The aim of the
      present study was to explore the conformational and thermal properties of
      phaseolin in the presence of protein structural perturbants by intrinsic
      fluorescence emission spectroscopy and differential scanning calorimetry. Raman
      spectroscopy was also used to characterise the secondary structures of phaseolin.
      RESULTS: The Raman spectrum of phaseolin indicated that beta-sheets and random
      coils were the major secondary structures. Intrinsic fluorescence emission
      spectroscopy confirmed the structural peculiarity and compactness of phaseolin,
      as evidenced by the absence of any shift in emission maximum (lambda(max)) in the
      presence of structural perturbants such as sodium dodecyl sulfate (SDS),
      guanidine hydrochloride, urea and dithiothreitol (DTT). Increasing NaCl
      concentration enhanced the thermal stability of phaseolin. Addition of chaotropic
      salts (1 mol L(-1)) caused progressive decreases in thermal stability following
      the lyotropic series of anions. Decreases in thermal denaturation temperature
      (T(d)) and enthalpy change (DeltaH) were observed in the presence of protein
      perturbants such as SDS, urea and ethylene glycol, indicating partial
      denaturation and a decrease in thermal stability. DTT and N-ethylmaleimide had
      little effect on the thermal properties of phaseolin, confirming that phaseolin,
      a 7S globulin, is devoid of inter-polypeptide disulfide bonds. CONCLUSION: The
      data presented here demonstrate the contributions of hydrophobic and
      electrostatic interactions and hydrogen bonding to the conformational stability
      of phaseolin.

PMID- 20815041
TI  - Exploitation of dietary tannins to improve rumen metabolism and ruminant
      nutrition.
AB  - Tannins (hydrolysable and condensed tannin) are polyphenolic polymers of
      relatively high molecular weight with the capacity to form complexes mainly with
      proteins due to the presence of a large number of phenolic hydroxyl groups. They
      are widely distributed in nutritionally important forage trees, shrubs and
      legumes, cereals and grains, which are considered as anti-nutritional compounds
      due to their adverse effects on intake and animal performance. However, tannins
      have been recognised to modulate rumen fermentation favourably such as reducing
      protein degradation in the rumen, prevention of bloat, inhibition of
      methanogenesis and increasing conjugated linoleic acid concentrations in ruminant
      derived foods. The inclusion of tannins in diets has been shown to improve body
      weight and wool growth, milk yields and reproductive performance. However, the
      beneficial effects on rumen modulation and animal performance have not been
      consistently observed. This review discusses the effects of tannins on nitrogen
      metabolism in the rumen and intestine, and microbial populations (bacteria,
      protozoa, fungi and archaea), metabolism of tannins, microbial tolerance
      mechanisms to tannins, inhibition of methanogenesis, ruminal biohydrogenation
      processes and performance of animals. The discrepancies of responses of tannins
      among different studies are attributed to the different chemical structures
      (degree of polymerisation, procyanidins to propdelphinidins, stereochemistry and
      C-C bonding) and concentrations of tannins, and type of diets. An establishment
      of structure-activity relationship would be required to explain differences among
      studies and obtain consistent beneficial tannin effects.

PMID- 20815042
TI  - Immunohistochemical expression of CDX2, beta-catenin, and TP53 in inflammatory
      bowel disease-associated colorectal cancer.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) exposes patients to an increased
      risk of colorectal cancer (i-CRC) and differences between i-CRC and sporadic
      colorectal cancer (s-CRC) pathogenesis were reported. In s-CRC, studies indicate
      abnormalities in the tumor-suppressor gene Cdx2. This study compared CDX2, beta
      catenin, and TP53 expression in i-CRC, s-CRC, noncancer IBD, and normal control
      colonic mucosa. METHODS: Expression was investigated by immunohistochemistry in
      10 normal, 20 s-CRC, 11 noncancer colonic IBD and 30 i-CRC samples, and in four
      samples of Crohn's disease (CD)-associated small bowel adenocarcinoma (i-SBA).
      RESULTS: In normal and noncancer IBD samples, CDX2 was confined to the
      colonocytes nuclei. CDX2 expression was normal in 90% of i-CRC, regardless of
      tumor differentiation or inflammation intensity. By contrast, CDX2 expression was
      altered in 45% s-CRC, particularly at the front of invasion in undifferentiated
      tumors. beta-Catenin was restricted to cell membrane in all controls, in 91%
      noncancer IBD, and in 84% i-CRC samples, whereas 35% s-CRC showed cytoplasmic
      redistribution and exclusive nuclear staining at the front of invasion. TP53 was
      strongly and homogeneously expressed in i-CRC nuclei compared to normal control
      or s-CRC, and increases with inflammation intensity. Nested or diffuse TP53 was
      found in 81.8% of noncancer IBD samples with a higher proportion of TP53
      expressing cells in the most inflamed samples. CDX2, beta-catenin, and TP53
      expression in CD-associated SBA appears similar to that of i-CRC. Neither Cdx2
      nor beta-catenin alterations are prominent features of i-CRC. CONCLUSIONS: In i
      CRC and CD-associated SBA, carcinogenesis is associated early with p53 mutations
      and to inflammation intensity.

PMID- 20815043
TI  - Sex-specific outcomes following revascularization with zotarolimus-eluting
      stents: comparison of angiographic and late-term clinical results.
AB  - OBJECTIVES: We examined angiographic and late-term clinical outcomes according to
      sex in recent percutaneous coronary intervention (PCI) trials involving
      zotarolimus-eluting stents (ZES). BACKGROUND: Differences in outcome between men
      and women undergoing PCI have been inconsistently described with bare metal and
      first-generation drug-eluting stents. METHODS: Clinical and angiographic outcomes
      among ZES-treated patients were evaluated by sex using propensity score modeling
      in a patient-level systematic overview of six trials and were also compared to
      patients receiving bare metal stents (BMS). RESULTS: Among 2,132 patients, 608
      were female (28.5%). Compared to men, women were older and more frequently had
      diabetes, hypertension, and a smaller reference vessel diameter (P < 0.05 for
      all). For both sexes, the relative reductions in 8-month angiographic binary
      restenosis and late lumen loss were statistically significant and of similar
      extent with ZES compared to BMS. By 2 years, treatment with ZES resulted in
      significantly lower target vessel revascularization (TVR) and target vessel
      failure (TVF; 10.0% vs. 21.5%, P = 0.0003) among women that paralleled risk
      reductions for men. However, among ZES-treated patients, 2-year rates of TVR
      (8.2% vs. 10.4%, P = 0.005) and TVF (9.9% vs. 12.8%, P = 0.004) were
      significantly lower among women, although rates of death and myocardial
      infarction were similar. CONCLUSIONS: Despite greater baseline clinical and
      angiographic risk than men, women undergoing PCI with ZES compared to BMS
      experienced significant reductions in angiographic restenosis and repeat
      revascularization yet similar safety. Among all patients treated with ZES, late
      term safety and efficacy outcomes are similar, if not lower, among women compared
      to men.

PMID- 20815044
TI  - Trans-catheter closure of patent ductus arteriosus-What is the best device?
AB  - BACKGROUND: Over the past three decades, transcatheter occlusion of patent ductus
      arteriosus (PDA) has evolved to be the procedure of choice. Gianturco and Flipper
      coils are the most commonly used coils in the United States for closure of small
      and moderate size PDAs. For larger PDAs, interventionalists in the United States
      commonly use the Amplatzer Duct Occluder (ADO) and those in Europe use the ADO or
      the Nit-Occlud Coils (NOC). A comparison between Gianturco coils, Flipper coils,
      ADO, and NOC has never been made. OBJECTIVE: To compare the success and
      complication rate associated with the four different devices used for
      transcatheter closure of PDA. Success was defined as complete closure of PDA with
      absence of a residual shunt (R.S.) at six months follow-up. METHODS: Two
      institutions collaborated in combining their data to evaluate the results of
      transcatheter closure of PDA. RESULTS: Totally, 546 patients underwent successful
      PDA occlusion at both institutions. Gianturco and Flipper coils were used in 120
      (22%) and 119 (22%) patients respectively. A total of 152 (28%) patients received
      ADO and 155 (28%) patients received NOC. Immediate R.S. were noted in 226 (41.4%)
      patients in the entire study group with the NOC group having the highest
      percentage of R.S. (80/155, 51.6%, P = 0.004). Of the 484 patients with follow-up
      echocardiograms at 6 months, 35 (7.2%) patients had persistent R.S. The NOC
      (3/143, 2.1%) and ADO (5/150, 3.3%) groups had the least R.S. at six months
      follow-up. CONCLUSION: Per our definition of success, the Nit-Occlud coils and
      the Amplatzer duct-occluder devices had significantly higher success rate for PDA
      occlusion versus the coils. (c) 2010 Wiley-Liss, Inc.

PMID- 20815045
TI  - Comparison of three-year clinical outcomes between sirolimus-versus paclitaxel
      eluting stents in diabetic patients: prospective randomized multicenter trial.
AB  - BACKGROUND: Three-year follow-up of major adverse cardiovascular event (MACE)
      (death, nonfatal myocardial infarction, target lesion revascularization) and the
      predictors of MACEs in diabetic patients after sirolimus-eluting stent (SES) or
      paclitaxel-eluting stent (PES) implantation have not been reported. METHODS:
      Diabetic patients with de novo coronary lesions (169 patients with 190 lesions)
      were randomly assigned prospectively to either SES or PES. RESULTS: Baseline
      characteristics were similar between the two groups. The rates of MACEs [5.9% (n
      = 5) in the SES vs. 9.5% (n = 8) in the PES Group, P = 0.374] and definite stent
      thrombosis [1.2% (n = 1) in the SES vs. 3.6% (n = 3) in the PES Group, P = 0.368]
      were similar in the two groups during the three-year follow-up. Multivariate
      logistic analysis showed that insulin treatment was the only independent
      predictor of MACE [odds ratio (OR) 8.60, 95% confidence interval (CI) 3.25-22.76,
      P < 0.001] and target vessel revascularization (TVR) (OR 9.50, 95% CI 3.07-29.44,
      P < 0.001) during the three-year follow-up. CONCLUSIONS: The rates of MACEs, TVR,
      and stent thrombosis during the three-year follow-up were similar in the SES and
      PES Groups. Insulin treatment was a main predictor of MACEs and TVR during the
      three-year follow-up after either SES or PES implantation.

PMID- 20815046
TI  - Mucinous carcinoma of the breast is genomically distinct from invasive ductal
      carcinomas of no special type.
AB  - Mucinous carcinomas are a rare entity accounting for up to 2% of all breast
      cancers, which have been shown to display a gene expression profile distinct from
      that of invasive ductal carcinomas of no special type (IDC-NSTs). Here, we have
      defined the genomic aberrations that are characteristic of this special type of
      breast cancer and have investigated whether mucinous carcinomas might constitute
      a genomic entity distinct from IDC-NSTs. Thirty-five pure and 11 mixed mucinous
      breast carcinomas were assessed by immunohistochemistry using antibodies against
      oestrogen receptor (ER), progesterone receptor, HER2, Ki67, cyclin D1, cortactin,
      Bcl-2, p53, E-cadherin, basal markers, neuroendocrine markers, and WT1. Fifteen
      pure mucinous carcinomas and 30 grade- and ER-matched IDC-NSTs were
      microdissected and subjected to high-resolution microarray-based comparative
      genomic hybridization (aCGH). In addition, the distinct components of seven mixed
      mucinous carcinomas were microdissected separately and subjected to aCGH. Pure
      mucinous carcinomas consistently expressed ER (100%), lacked HER2 expression
      (97.1%), and showed a relatively low level of genetic instability. Unsupervised
      hierarchical cluster analysis revealed that pure mucinous carcinomas were
      homogeneous and preferentially clustered together, separately from IDC-NSTs. They
      less frequently harboured gains of 1q and 16p and losses of 16q and 22q than
      grade- and ER-matched IDC-NSTs, and no pure mucinous carcinoma displayed
      concurrent 1q gain and 16q loss, a hallmark genetic feature of low-grade IDC
      NSTs. Finally, both components of all but one mixed mucinous carcinoma displayed
      similar patterns of genetic aberrations and preferentially clustered together
      with pure mucinous carcinomas on unsupervised clustering analysis. Our results
      demonstrate that mucinous carcinomas are more homogeneous between themselves at
      the genetic level than IDC-NSTs. Both components of mixed mucinous tumours are
      remarkably similar at the molecular level to pure mucinous cancers, suggesting
      that mixed mucinous carcinomas may be best classified as variants of mucinous
      cancers rather than of IDC-NSTs.

PMID- 20815047
TI  - Analysis of alpha hemoglobin stabilizing protein overexpression in murine beta
      thalassemia.
AB  - Excess free alpha-globin is cytotoxic and contributes to the pathophysiology of b
      thalassemia. Alpha hemoglobin stabilizing protein (AHSP) is a molecular chaperone
      that binds free alpha-globin to promote its folding and inhibit its ability to
      produce damaging reactive oxygen species. Reduced AHSP levels correlate with
      increased severity of b-thalassemia in some human cohorts, but causal mechanistic
      relationships are not established for these associations. We used transgenic and
      lentiviral gene transfer methods to investigate whether supraphysiologic AHSP
      levels could mitigate the severity of b-thalassemia intermedia by providing an
      increased sink for the excess pool of alpha-globin chains. We tested wild-type
      AHSP and two mutant versions with amino acid substitutions that confer 3- or 13
      fold higher affinity for alpha-globin. Erythroid overexpression of these AHSP
      proteins up to 11-fold beyond endogenous levels had no major effects on
      hematologic parameters in b-thalassemic animals. Our results demonstrate that
      endogenous AHSP is not limiting for a-globin detoxification in a murine model of
      b-thalassemia.

PMID- 20815050
TI  - Common data elements in radiologic imaging of traumatic brain injury.
AB  - Traumatic brain injury (TBI) has a poorly understood pathology. Patients suffer
      from a variety of physical and cognitive effects that worsen as the type of
      trauma worsens. Some noninvasive insights into the pathophysiology of TBI are
      possible using magnetic resonance imaging (MRI), computed tomography (CT), and
      many other forms of imaging as well. A recent workshop was convened to evaluate
      the common data elements (CDEs) that cut across the imaging field and given the
      charge to review the contributions of the various imaging modalities to TBI and
      to prepare an overview of the various clinical manifestations of TBI and their
      interpretation. Technical details regarding state-of-the-art protocols for both
      MRI and CT are also presented with the hope of guiding current and future
      research efforts as to what is possible in the field. Stress was also placed on
      the potential to create a database of CDEs as a means to best record information
      from a given patient from the reading of the images.

PMID- 20815049
TI  - Imaging biomarkers of cardiovascular disease.
AB  - Cardiovascular disease (CVD) is a leading cause of morbidity and mortality
      worldwide. Current clinical techniques that rely on stenosis measurement alone
      appear to be insufficient for risk prediction in atherosclerosis patients. Many
      novel imaging methods have been developed to study atherosclerosis progression
      and to identify new features that can predict future clinical risk. MRI of
      atherosclerotic vessel walls is one such method. It has the ability to
      noninvasively evaluate multiple biomarkers of the disease such as luminal
      stenosis, plaque burden, tissue composition and plaque activity. In addition, the
      accuracy of in vivo MRI has been validated against histology with high
      reproducibility, thus paving the way for application to epidemiological studies
      of disease pathogenesis and, by serial MRI, in monitoring the efficacy of
      therapeutic intervention. In this review, we describe the various MR techniques
      used to evaluate aspects of plaque progression, discuss imaging-based
      measurements (imaging biomarkers), and also detail their validation. The
      application of plaque MRI in clinical trials as well as emerging imaging
      techniques used to evaluate plaque compositional features and biological
      activities are also discussed.

PMID- 20815051
TI  - Non-invasive visualization of basilar artery perforators with 7T MR angiography.
AB  - PURPOSE: To visualize the perforating arteries originating from basilar artery
      (BA) by using ultra-high resolution 7T MR angiography (MRA) and optimizing MR
      parameters as well as radio frequency (RF) coils, which may provide important
      information for neurosurgery and understanding diseases of the pons, but was
      unable to clearly visualize with conventional MRA techniques. MATERIALS AND
      METHODS: Seven healthy volunteers (five males and two females, age [mean +/- SD]
      = 28.71 +/- 7.54 years) were scanned using optimized MR parameters to obtain
      images of pontine arteries (PAs) originating from the main trunk of BA. Two
      different volume coils and a phased array coil were designed and compared for
      this study. The images obtained at 7T MRA were compared with those at 1.5T and 3T
      MRA. RESULTS: The results showed that PA imaging at 7T MRI consistently provided
      clearly identifiable vessels, which were difficult to visualize in MR angiograms
      obtained at 1.5T and 3T MRIs. Volume RF coils had higher sensitivity for the
      center of the brain, which enhanced PA imaging compared to phased array coil. The
      average number of PA branches in all seven subjects observable by 7T MRA was 7.14
      +/- 2.79, and the visualized PA branches were found to mainly propagating on the
      surface of the pons. CONCLUSION: We have demonstrated that ultra-high resolution
      7T MRA could delineate the PAs using optimized imaging parameters and volume RF
      coils compared to commercially available 1.5T and 3T MRIs.

PMID- 20815052
TI  - Manganese transport in the rat optic nerve evaluated with spatial- and time
      resolved magnetic resonance imaging.
AB  - PURPOSE: 1) To evaluate a novel theoretical model for in vivo axonal Mn(2+)
      transport with MRI data from the rat optic nerve (ON); and 2) to compare
      predictions from the new model with previously reported experimental data.
      MATERIALS AND METHODS: Time-resolved in vivo T(1)-weighted magnetic resonance
      imaging (MRI) of adult female Sprague-Dawley rat (n = 9) ON was obtained at
      different timepoints after intravitreal MnCl(2) injection. A concentration
      dependent and a rate-dependent function for the Mn(2+) retinal ganglion cell
      (RGC) axon entrance was convolved with three different transport functions and
      each model system was optimized to fit the ON data. RESULTS: The rate-limited
      input function gave a better fit to the data than the concentration-limited
      input. Simulations showed that the rate-limited input leads to a semilogarithmic
      relationship between injected dose and Mn(2+) concentration in the ON, which is
      in agreement with previously reported in vivo experiments. A random walk
      transport model and an anterograde predominant slow model gave a similar fit to
      the data, both better than an anterograde predominant fast model. CONCLUSION: The
      results indicate that Mn(2+) input into RGC axons is limited by a maximum
      entrance rate into the axons. Also, a wide range of apparent Mn(2+) transport
      rates seems to be involved, different from synaptic vesicle transport rates,
      meaning that manganese does not depict synaptic vesicle transport rates directly.

PMID- 20815053
TI  - Correlation of putative iron content as represented by changes in R2* and phase
      with age in deep gray matter of healthy adults.
AB  - PURPOSE: To establish a correlation between putative iron content using
      susceptibility weighted imaging (SWI) phase and T2* weighted magnitude values in
      the basal ganglia and the thalamus as a function of age in healthy human brains.
      MATERIALS AND METHODS: One hundred healthy adults (range, 20-69 years; mean, 43
      years) were evaluated for this study using a gradient echo sequence. The original
      magnitude and high pass filtered phase data were analyzed as proxy variables for
      iron content in the substantia nigra, red nucleus, globus pallidus, putamen,
      caudate nucleus, thalamus, and pulvinar thalamus. Each structure was broken into
      two parts, a high iron content region and a low iron content region. RESULTS:
      Both magnitude and phase data showed an increase in putative iron content with
      age. However, the high iron content region revealed two new pieces of
      information: both the average iron content per pixel and the area of high iron
      increased with age. Furthermore, significant increase in iron uptake as a
      function of age was found past the age of 40. CONCLUSION: A two region of
      interest analysis of iron is a much more sensitive means to evaluate iron content
      change over time. Contrary to the current belief that iron content increases
      level off with age, the putative iron deposition in the high iron content region
      is seen to increase with age.

PMID- 20815054
TI  - In vivo magnetic resonance elastography of human brain at 7 T and 1.5 T.
AB  - PURPOSE: To investigate the feasibility of quantitative in vivo ultrahigh field
      magnetic resonance elastography (MRE) of the human brain in a broad range of low
      frequency mechanical vibrations. MATERIALS AND METHODS: Mechanical vibrations
      were coupled into the brain of a healthy volunteer using a coil-driven actuator
      that either oscillated harmonically at single frequencies between 25 and 62.5 Hz
      or performed a superimposed motion consisting of multiple harmonics. Using a
      motion sensitive single-shot spin-echo echo planar imaging sequence shear wave
      displacements in the brain were measured at 1.5 and 7 T in whole-body MR
      scanners. Spatially averaged complex shear moduli were calculated applying
      Helmholtz inversion. RESULTS: Viscoelastic properties of brain tissue could be
      reliably determined in vivo at 1.5 and 7 T using both single-frequency and
      multifrequency wave excitation. The deduced dispersion of the complex modulus was
      consistent within different experimental settings of this study for the measured
      frequency range and agreed well with literature data. CONCLUSION: MRE of the
      human brain is feasible at 7 T. Superposition of multiple harmonics yields
      consistent results as compared to standard single-frequency based MRE. As such,
      MRE is a system-independent modality for measuring the complex shear modulus of
      in vivo human brain in a wide dynamic range.

PMID- 20815055
TI  - Functional connectivity in blood oxygenation level-dependent and cerebral blood
      volume-weighted resting state functional magnetic resonance imaging in the rat
      brain.
AB  - PURPOSE: To directly compare functional connectivity and spatiotemporal dynamics
      acquired with blood oxygenation level-dependent (BOLD) and cerebral blood volume
      (CBV)-weighted functional magnetic resonance imaging (fMRI) in anesthetized rats.
      MATERIALS AND METHODS: A series of BOLD images were acquired in 10 rats followed
      by CBV-weighted images created by injection of ultrasmall iron oxide particles.
      Functional connectivity, spectral information, and spatiotemporal dynamics were
      compared for the BOLD and CBV-weighted resting state scans. RESULTS: BOLD scans
      exhibited higher cross-correlation values compared to CBV-weighted scans, but the
      spatial patterns of correlation were similar. The BOLD spectrum contains power
      evenly distributed throughout the low-frequency range while the CBV power
      spectrum exhibited a high power peak localized to approximately 0.2 Hz. Both BOLD
      and CBV resting state scans showed similar propagating waves of activity along
      the cortex from the SII toward MI; however, these waves were detected more often
      in BOLD scans than in CBV scans. CONCLUSION: While the power spectrum of the CBV
      signal is different from that of the BOLD signal, both connectivity maps and
      spatiotemporal dynamics are similar for the two modalities. Further experiments
      should address the relationship between spontaneous neural activity, local
      changes in metabolism, and hemodynamic fluctuations to elucidate the origins of
      the BOLD and CBV signals.

PMID- 20815056
TI  - Association between contrast-enhanced MR images and blood-brain barrier
      disruption following transcranial focused ultrasound.
AB  - PURPOSE: To investigate the correlation between the contrast-enhanced magnetic
      resonance imaging (MRI) signal and the duration of blood-brain barrier (BBB)
      disruption induced by focused ultrasound (FUS). MATERIALS AND METHODS: FUS was
      applied to 45 rat brains in the presence of microbubbles, and these rats were
      scanned on a 3T MRI system at several timepoints. The rat brains were then
      studied using contrast-enhanced spin echo T1-weighted images. At the same time,
      BBB disruption was evaluated based on Evans blue (EB) extravasation. The
      relationship between the normalized signal intensity change of the MRI and EB
      extravasation was analyzed by least-squares linear regression and the calculation
      of correlation coefficients. RESULTS: When MRI enhancement was quantitatively
      evaluated by EB extravasation, a strong correlation between the normalized signal
      intensity change of the MRI and EB extravasation was identified during BBB
      disruption after sonication. However, the correlation coefficient decreased as
      BBB closure occurred after sonication ended. CONCLUSION: The contrast-enhanced
      MRI signal can potentially be used to evaluate the amount of chemotherapeutic
      agents entering the targeted tissue, but the accuracy of the assessment will be
      affected by the time interval since sonication.

PMID- 20815057
TI  - Effect of the extracranial deep brain stimulation lead on radiofrequency heating
      at 9.4 Tesla (400.2 MHz).
AB  - PURPOSE: To study the effect of the extracranial portion of a deep brain
      stimulation (DBS) lead on radiofrequency (RF) heating with a transmit and receive
      9.4 Tesla head coil. MATERIALS AND METHODS: The RF heating was studied in four
      excised porcine heads (mean animal head weight = 5.46 +/- 0.14 kg) for each of
      the following two extracranial DBS lead orientations: one, parallel to the coil
      axial direction; two, perpendicular to the coil axial direction (i.e.,
      azimuthal). Temperatures were measured using fluoroptic probes at four locations:
      one, scalp; two, near the second DBS lead electrode-brain contact; three, near
      the distal tip of the DBS lead; and four, air surrounding the head. A continuous
      wave RF power was delivered to each head for 15 min using the coil. Net,
      delivered RF power was measured at the coil (mean whole head average specific
      absorption rate = 2.94 +/- 0.08 W/kg). RESULTS: RF heating was significantly
      reduced when the extracranial DBS lead was placed in the axial direction
      (temperature change = 0-5 degrees C) compared with the azimuthal direction
      (temperature change = 1-27 degrees C). CONCLUSION: Development of protocols seems
      feasible to keep RF heating near DBS electrodes clinically safe during ultra-high
      field head imaging.

PMID- 20815058
TI  - Quantification of myocardial strain at early systole in mouse heart: restoration
      of undeformed tagging grid with single-point HARP.
AB  - PURPOSE: To develop accurate strain and torsion quantification method for the
      assessment of myocardial contraction in mice by MRI tagging. MATERIALS AND
      METHODS: Ventricular wall motion at baseline and during beta-adrenergic
      stimulation was assessed in mice using MRI tagging. Myocardial strain and torsion
      were quantified using finite element analysis method. A harmonic phase (HARP)
      based method was developed for the restoration of undeformed taglines for more
      accurate calculation of myocardial wall strain and torsion. RESULTS: Myocardial
      deformation was observed at early systole (<20 msec after QRS) both at baseline
      and during beta-adrenergic stimulation. The HARP-based method allowed robust
      restoration of undeformed taglines that can be used as the reference in finite
      element analysis of the tagged images. Without such correction for myocardial
      deformation in the reference image, inaccuracy in strain quantification
      underestimated significant strain development at early systole in dobutamine
      stimulated hearts. CONCLUSION: The HARP-based method developed in the current
      study enabled automated restoration of undeformed taglines in mouse hearts,
      leading to more accurate calculation of myocardial wall strain and torsion during
      dobutamine stimulation.

PMID- 20815059
TI  - Negative predictive value of normal adenosine-stress cardiac MRI in the
      assessment of coronary artery disease and correlation with semiquantitative
      perfusion analysis.
AB  - PURPOSE: To prospectively determine the negative predictive value of normal
      adenosine stress cardiac MR (CMR) in routine patients referred for evaluation of
      coronary artery disease (CAD), predominantly with intermediate to high pretest
      risk. MATERIALS AND METHODS: Consecutive patients referred for coronary
      angiography were examined in a 1.5 Tesla whole-body scanner before
      catheterization. A total of 158 patients with normal CMR on qualitative
      assessment were included, and semiquantitative perfusion analysis was performed.
      Significant CAD was regarded as luminal narrowing of >or=70% in coronary
      angiography. RESULTS: In the 158 study patients, negative predictive value of
      normal adenosine-stress CMR for significant CAD was 96.2% (for stenosis >or=90%:
      98.1%). True-negative and false-negative patients were comparable regarding
      clinical presentation, risk factors, and CMR findings. Semiquantitative perfusion
      analysis gave significantly prolonged arrival time index and peak time index in
      the false-negative group. Using cutoff values >1.8 for arrival time index or >1.2
      for peak time index, the CMR negative predictive value increased to 98.7% (for
      stenosis >or=90%: to 100%). CONCLUSION: The very high negative predictive value
      for CAD supports CMR-based decision making for the indication to coronary
      angiography. Semiquantitative perfusion analysis seems promising to identify the
      small group of CAD patients not detectable by qualitative CMR assessment.

PMID- 20815060
TI  - Multiple-bolus dynamic contrast-enhanced MRI in the pancreas during a glucose
      challenge.
AB  - PURPOSE: To assess the feasibility of multiple-bolus dynamic contrast-enhanced
      (DCE) magnetic resonance imaging (MRI) in the pancreas; to optimize the analysis;
      and to investigate application of the method to a glucose challenge in type 2
      diabetes. MATERIALS AND METHODS: A 4-bolus DCE-MRI protocol was performed on five
      patients with type 2 diabetes and 11 healthy volunteers during free-breathing.
      Motion during the dynamic time series was corrected for using a model-driven
      nonlinear registration. A glucose challenge was administered intravenously
      between the first and second DCE-MRI acquisition in all patients and in seven of
      the healthy controls. RESULTS: Image registration improved the reproducibility of
      the DCE-MRI model parameters across the repeated bolus-acquisitions in the
      healthy controls with no glucose challenge (eg, coefficient of variation for
      K(trans) improved from 38% to 28%). Native tissue T(1) was significantly lower in
      patients (374 +/- 68 msec) compared with volunteers (519 +/- 41 msec) but there
      was no significant difference in any of the baseline DCE-MRI parameters. No
      effect of glucose challenge was observed in either the patients or healthy
      volunteers. CONCLUSION: Multiple bolus DCE-MRI is feasible in the pancreas and is
      improved by nonlinear image registration but is not sensitive to the effects of
      an intravenous glucose challenge.

PMID- 20815061
TI  - Gadoxetic acid-enhanced MRI versus multiphase multidetector row computed
      tomography for evaluating the viable tumor of hepatocellular carcinomas treated
      with image-guided tumor therapy.
AB  - PURPOSE: To compare the diagnostic performance of gadoxetic acid-enhanced MRI
      with that of multi-phase 40- or 64-multidetector row computed tomography (MDCT)
      to evaluate viable tumors of hepatocellular carcinomas (HCCs) treated with image
      guided tumor therapy. MATERIALS AND METHODS: A total of 108 patients with 162
      HCCs (56 lesions with viable tumor and 106 without viable tumor) treated by means
      of transcatheter arterial chemoembolization or radiofrequency ablation were
      retrospectively included in this study. All patients underwent multi-phase CT at
      40- or 64-MDCT and gadoxetic acid-enhanced MRI using 3.0 Tesla (T). Two observers
      independently and randomly reviewed the CT and MR images of the treated lesions.
      The diagnostic performance of two techniques for the evaluation of the viable
      tumors in the treated lesions was assessed with a receiver operating
      characteristic (ROC) analysis. RESULTS: For each observer, the areas under the
      ROC curve were 0.953 and 0.969 for MRI, and 0.870 and 0.888 for MDCT (P < 0.05).
      The diagnostic accuracies (96.3% for each observer) and sensitivities (92.9% and
      96.4%) of MRI in two observers were significantly higher than those (82.7% and
      80.9%, 53.6% for each observer, respectively) of MDCT (P < 0.001). The negative
      predictive values (96.3% and 98.1%) of MRI in two observers were significantly
      higher than those (80.0% and 79.5%) of MDCT (P < 0.001). For each observer,
      specificities and positive predictive values did not differ significantly between
      the two techniques (P > 0.05). CONCLUSION: Gadoxetic acid-enhanced MRI shows
      better diagnostic performance than that of MDCT for evaluating the viable tumors
      of HCCs treated with image-guided tumor therapy.

PMID- 20815062
TI  - MRI quantification of splenic iron concentration in mouse.
AB  - PURPOSE: To quantify hepatic and splenic iron load, which is a critical issue for
      iron overload disease diagnosis. MRI is useful to noninvasively determine liver
      iron concentration, but not proven to be adequate for robust evaluation of
      splenic iron load. We evaluated the usefulness of MRI-derived parameters to
      determine splenic iron concentration in mice. MATERIALS AND METHODS: A mouse
      model of experimental iron load was used. Multi-echo spin-echo images of liver
      and spleen were acquired at 4.7 Tesla. The parameters were tested at all echoes
      with and without an external reference. Splenic and hepatic iron concentrations
      were determined using biochemical assay as the gold standard. RESULTS: Our
      results show that (i) use of an internal or external reference is essential; (ii)
      optimal echo times were TE = 19.5 ms and TE = 32.5 ms for the liver and spleen,
      respectively; (iii) in the liver, the relationship between biochemical and MRI
      iron concentration determinations is logarithmic; (iv) in the spleen, the best
      relationship is an inverse function. CONCLUSION: A single spin-echo sequence
      allows robust estimation of hepatic and splenic iron content. Parameters
      classically used for hepatic iron concentration cannot be applied to splenic iron
      determination, which requires both the specific sequence and the adapted fitting
      function.

PMID- 20815063
TI  - Interobserver and intraobserver variability of the apparent diffusion coefficient
      in treated malignant hepatic lesions on a 3.0T machine: measurements in the whole
      lesion versus in the area with the most restricted diffusion.
AB  - PURPOSE: To assess the inter/intraobserver variability of apparent diffusion
      coefficient (ADC) measurements in treated hepatic lesions and to compare ADC
      measurements in the whole lesion and in the area with the most restricted
      diffusion (MRDA). MATERIALS AND METHODS: Twenty-five patients with treated
      malignant liver lesions were examined on a 3.0T machine. After agreeing on the
      best ADC image, two readers independently measured the ADC values in the whole
      lesion and in the MRDA. These measurements were repeated 1 month later. The Bland
      Altman method, Spearman correlation coefficients, and the Wilcoxon signed-rank
      test were used to evaluate the measurements. RESULTS: Interobserver variability
      for ADC measurements in the whole lesion and in the MRDA was 0.17 x 10(-3)
      mm(2)/s [-0.17, +0.17] and 0.43 x 10(-3) mm(2)/s [-0.45, +0.41], respectively.
      Intraobserver limits of agreement could be as low as [-0.10, +0.12] 10(-3)
      mm(2)/s and [-0.20, +0.33] 10(-3) mm(2)/s for measurements in the whole lesion
      and in the MRDA, respectively. CONCLUSION: A limited variability in ADC
      measurements does exist, and it should be considered when interpreting ADC values
      of hepatic malignancies. This is especially true for the measurements of the
      minimal ADC.

PMID- 20815064
TI  - Post-processing correction of the endorectal coil reception effects in MR
      spectroscopic imaging of the prostate.
AB  - PURPOSE: To develop and validate a post-processing correction algorithm to remove
      the effect of the inhomogeneous reception profile of the endorectal coil on MR
      spectroscopic imaging (MRSI) data. MATERIALS AND METHODS: A post-processing
      algorithm to correct for the endorectal coil reception effects on MRSI data was
      developed based upon theoretical modeling of the endorectal coil reception
      profile and of the spatial saturation pulse profiles. This algorithm was
      evaluated on three-dimensional (3D) MRSI data acquired at 3T from a uniform
      phantom and from 18 patients with known or suspected prostate cancer. RESULTS:
      For the phantom data, the coefficient of variation of metabolite peak areas
      decreased 16% to 46% and the peak area distributions became more Gaussian with
      correction, as demonstrated by higher Q-Q plot linear correlations (R(2) = 0.98
      +/- 0.007 vs. R(2) = 0.89 +/- 0.066). Across the 18 patients, the mean
      coefficient of variation for suppressed water decreased significantly, from 0.95
      +/- 0.18, to 0.66 +/- 0.11, (P < 10(-6), paired t-test) and the linear
      correlations of the Q-Q plots for the suppressed water increased from R(2) = 0.91
      to R(2) = 0.95 (P = 0.0083, paired t-test) with correction. CONCLUSION: An
      algorithm for reducing the effect of the inhomogeneous reception profile in
      endorectal coil acquired 3D MRSI prostate data was demonstrated, illustrating
      increased homogeneity and more Gaussian peak area distributions.

PMID- 20815065
TI  - Susceptibility mapping as a means to visualize veins and quantify oxygen
      saturation.
AB  - PURPOSE: To create an orientation-independent, 3D reconstruction of the veins in
      the brain using susceptibility mapping. MATERIALS AND METHODS: High-resolution,
      high-pass filtered phase images usually used for susceptibility weighted imaging
      (SWI) were used as a source for local magnetic field behavior. These images were
      subsequently postprocessed using an inverse procedure to generate susceptibility
      maps of the veins. Regularization and interpolation of the data in k-space of the
      phase images were used to reduce reconstruction artifacts. To understand the
      effects of artifacts, and to fine-tune the methodology, simulations of blood
      vessels were performed with and without noise. RESULTS: With sufficient
      resolution, major veins in the brain could be visualized with this approach. The
      usual geometry-dependent phase dipole effects are removed by this processing,
      leaving basically images of the veins. Different sized vessels show a different
      level of contrast depending on their partial volume effects. Vessels that are 8
      mm or 16 mm in size show quantitative values expected for normal oxygen
      saturation levels. Smaller vessels show smaller values due to errors in the
      methodology and due to partial volume effects. Larger vessels show a bias toward
      a reduced susceptibility approaching 90% of the expected value. Limitations of
      the method and artifacts related to different sources of errors are demonstrated.
      CONCLUSION: Susceptibility maps can successfully create venograms of the brain
      with varying levels of contrast-to-noise depending on the size of the vessel.
      Partial volume effects render this approach more useful as an imaging tool or a
      visualization tool, although certain larger vessels have measured
      susceptibilities close to expected values associated with normal blood oxygen
      saturation levels.

PMID- 20815066
TI  - Flow-sensitive four-dimensional cine magnetic resonance imaging for offline blood
      flow quantification in multiple vessels: a validation study.
AB  - PURPOSE: To further validate the quantitative use of flow-sensitive four
      dimensional velocity encoded cine magnetic resonance imaging (4D VEC MRI) for
      simultaneously acquired venous and arterial blood flow in healthy volunteers and
      for abnormal flow in patients with congenital heart disease. MATERIALS AND
      METHODS: Stroke volumes (SV) obtained in arterial and venous thoracic vessels
      were compared between standard two-dimensional (2D), 4D VEC MRI with and without
      respiratory navigator gating (gated/nongated) in volunteers (n = 7). In addition,
      SV and regurgitation fractions (RF) measured in aorta or pulmonary trunk of
      patients with malformed and/or insufficient valves (n = 10) were compared between
      2D and nongated 4D VEC MRI methods. RESULTS: In volunteers and patients, Bland
      Altman tests showed excellent agreement between 2D, gated, and nongated 4D VEC
      MRI obtained quantitative blood flow measurements. The bias between 2D and gated
      4D VEC MRI was <0.5 mL for SV; between 2D and nongated 4D VEC MRI the bias was
      <0.7 mL for SV and <1% for RF. CONCLUSION: Blood flow can be quantified
      accurately in arterial, venous, and pathological flow conditions using 4D VEC
      MRI. Nongated 4D VEC MRI has the potential to be suited for clinical use in
      patients with congenital heart disease who require flow acquisitions in multiple
      vessels.

PMID- 20815067
TI  - Pyrolytic graphite foam: a passive magnetic susceptibility matching material.
AB  - PURPOSE: To evaluate a novel soft, lightweight cushion that can match the
      magnetic susceptibility of human tissue. The magnetic susceptibility difference
      between air and tissue produces field inhomogeneities in the B(0) field, which
      leads to susceptibility artifacts in magnetic resonance imaging (MRI) studies.
      MATERIALS AND METHODS: Pyrolytic graphite (PG) microparticles were uniformly
      embedded into a foam cushion to reduce or eliminate field inhomogeneities at
      accessible air and tissue interfaces. 3T MR images and field maps of an
      air/water/PG foam phantom were acquired. Q measurements on a 4T tuned head coil
      and pulse sequence heating tests at 3T were also performed. RESULTS: The PG foam
      improved susceptibility matching, reduced the field perturbations in phantoms,
      does not heat, and is nonconductive. CONCLUSION: The susceptibility matched PG
      foam is lightweight, safe for patient use, adds no noise or MRI artifacts, is
      compatible with radiofrequency coil arrays, and improves B(0) homogeneity, which
      enables more robust MR studies.

PMID- 20815068
TI  - Lymphoepithelial cysts in the pancreas: MRI of two cases with emphasis of
      diffusion-weighted imaging characteristics.
AB  - Pancreatic lymphoepithelial cysts (LECs) are rare pancreatic cystic lesions
      filled with keratinized material, lined by mature, keratinizing squamous
      epithelium and surrounded by lymphoid tissue containing few lymphoid follicles.
      We report two cases of surgically confirmed pancreatic LECs showing a profound
      restriction of water molecules on diffusion-weighted (DWI) magnetic resonance
      imaging (MRI). For pancreatic cystic lesions showing lack of molecular motion on
      DWI with or without thin marginal enhancement on contrast material-enhanced
      imaging, LECs consisting of internally keratinized materials with restricted
      diffusion should be considered in differential diagnoses even though they cannot
      always be easy to distinguish from other focal pancreatic lesions containing
      mucin, blood clot, or nonliquefactive necrosis.

PMID- 20815069
TI  - Sealed-off spontaneous perforation of a pyometra diagnosed preoperatively by
      magnetic resonance imaging: a case report.
AB  - Spontaneous perforation is a very rare complication of pyometra. The clinical
      findings of perforated pyometra usually mimic perforation of the gastrointestinal
      tract. In most cases a correct diagnosis can be made only by laparotomy. In our
      case, the patient's pyometra was sealed and she complained only of mild abdominal
      pain and showed no signs of peritonitis. Ultrasonography and computed tomography
      (CT) findings were not suggestive of uterine rupture. However, T2-weighted
      magnetic resonance imaging (MRI) demonstrated a full thickness defect of the
      myometrium. We discuss the CT and MRI findings that confirmed a correct diagnosis
      of perforated pyometra.

PMID- 20815070
TI  - Use of time resolved magnetic resonance imaging in the diagnosis of pelvic
      congestion syndrome.
AB  - We describe the efficacy of time-resolved MR angiography in diagnosing a case of
      pelvic congestion syndrome (PCS). MR angiography, using four-dimensional (4D)
      TRAK (Time-Resolved Angiography using Keyhole) technique was used in an 81-year
      old woman presenting with low backache, pelvic pain, and left pelvic fullness.
      Dynamic images were obtained in multiple vascular phases including arterial,
      arteriovenous, and venous phases. The high temporal resolution of 4D TRAK could
      demonstrate early retrograde left ovarian vein filling as well as multiple
      dilated pelvic varices, allowing the prospective diagnosis of PCS to be made.
      Although uncommon in this age group, the diagnosis was subsequently confirmed on
      conventional catheter venography with symptomatic relief after successful
      embolization of the incompetent left ovarian vein. The MRA and correlative
      catheter venography images are presented in this case report.

PMID- 20815071
TI  - Real-time noise cancellation for speech acquired in interactive functional
      magnetic resonance imaging studies.
AB  - PURPOSE: To present online scanner noise cancellation for speech acquired in
      functional magnetic resonance imaging (fMRI) studies. MATERIALS AND METHODS: An
      online active noise cancellation method for speech acquired in fMRI studies was
      developed. The approach consists of two automated steps: 1) creation of an MR
      noise template in a short "test" fMRI scan; 2) application of the template for
      automatic recognition and subtraction of the MR noise from the acquired
      microphone signal during an fMRI study. The method was applied in an experimental
      paradigm where a subject and an investigator communicated in an interactive
      verbal generation task during fMRI. RESULTS: By applying online active noise
      cancellation, the quality of the subject's speech was substantially improved. The
      present approach was found to be flexible, reliable, and easy to implement,
      providing a method for fMRI studies that investigate the neural correlates of
      interactive speech communication. CONCLUSION: Using online noise cancellation it
      is possible to improve the quality of acquired speech in fMRI. This approach may
      be recommended for interactive fMRI studies.

PMID- 20815072
TI  - Evaluation of intraneural ganglion cysts using three-dimensional fast spin echo
      cube.
AB  - PURPOSE: To compare conventional two-dimensional fast spin echo (FSE) MRI
      sequences with a three-dimensional FSE extended echo train acquisition method,
      known as Cube, in the evaluation of intraneural ganglion cysts. Also, to
      demonstrate that Cube enables the consistent identification and thorough
      characterization of the cystic joint connection, and therefore improves patient
      care by superior preoperative planning. MATERIALS AND METHODS: Six patients with
      intraneural ganglia in the knee region (five involving the peroneal and one the
      tibial nerve) were evaluated using both conventional FSE MR sequences and the
      Cube sequence. Studies were interpreted by the consensus of three board certified
      musculoskeletal radiologists and one peripheral nerve neurosurgeon. Surgical
      correlation was available in five of the six cases. RESULTS: Both imaging methods
      demonstrated the cysts and at least part of their joint connections after
      variable amount of postprocessing. Cube proved superior to conventional imaging
      in its ability to acquire isotropic data that could easily be reconstructed in
      any plane and its ability to resolve fine anatomical details. CONCLUSION: Cube is
      a new MR pulse sequence that enables the consistent identification of the
      intraneural ganglion cyst joint connection. We believe that improved
      visualization and characterization of the entire cyst will improve patient
      outcomes by facilitating more accurate surgical intervention.

PMID- 20815073
TI  - Comparison between areas with Gd-EOB-DTPA uptake and without in hepatocellular
      carcinomas on Gd-EOB-DTPA-enhanced hepatobiliary-phase MR imaging: pathological
      correlation.
AB  - PURPOSE: To determine histological and MR imaging differences between areas with
      Gd-EOB-DTPA (gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid) uptake
      and without in hepatocellular carcinomas (HCCs) as seen on Gd-EOB-DTPA-enhanced
      hepatobiliary-phase MR images. MATERIALS AND METHODS: This study included nine
      patients with nine histopathologically proven HCCs (mean size, 1.9 cm) that
      consisted of two portions of a non-hypointense (Gd-EOB-DTPA uptake) and
      hypointense area (no Gd-EOB-DTPA uptake) in one tumor as depicted on
      hepatobiliary-phase MR images. Two radiologists and one pathologist compared the
      histological and MR finding differences between the two portions in consensus.
      RESULTS: In eight specimens, non-hypointense areas of six specimens showed a
      green color and two specimens did not show a green color. Microscopically, two of
      nine showed a higher percentage of bile pigments in the non-hypointense area as
      compared to the hypointense area and the remaining seven showed no difference.
      Six were homogeneous Edmondson-Steiner grade II, and one was grade I. In two, non
      hypointense areas were grade II and hypointense areas were grade I. No difference
      between the two portions was found for necrosis, hemorrhage, fibrosis, and a
      fibrous capsule. Seven on T1/T2-weighted images and eight on arterial and portal
      phase images showed no different signal intensity between the two portions.
      CONCLUSION: Although macroscopically, a non-hypointense area of an HCC seen on GD
      EOB-DTPA-enhanced hepatobiliary-phase images may be associated with the area with
      a green color, no definite microscopic and MR imaging findings that could
      discriminate a non-hypointense from a hypointense area of an HCC was found.

PMID- 20815074
TI  - Respiratory motion compensated MR cholangiopancreatography at 3.0 Tesla.
AB  - PURPOSE: To reduce irregular respiratory motion-induced artifacts in free
      breathing prospective navigator-triggered three-dimensional (3D) MR
      cholangiopancreatography (MRCP). MATERIALS AND METHODS: A reference respiration
      model was estimated from the first-five respiration periods during the initial
      navigator scan. With the navigator information acquired before and after
      triggering, the un-acquired diaphragm position during the actual imaging was
      interpolated using the amplitude-scaled reference model. Craniocaudal
      translational motion during imaging was retrospectively corrected using the
      estimated diaphragm position. T2-weighted 3D MRCP data were acquired from 17
      healthy volunteers. For quantitative analysis, contrast-to-noise ratio (CNR) and
      relative contrast (RC) of the biliary tree and gallbladder were compared using
      the paired t-test. RESULTS: The CNR and RC of the biliary tree and gallbladder
      were significantly higher (P < 0.05) in the maximum intensity projection images
      after motion compensation. CONCLUSION: The proposed algorithm can be an effective
      tool to reduce the irregular respiratory motion-induced artifacts in 3D MRCP
      imaging.

PMID- 20815075
TI  - Reversed laminar appearance of articular cartilage by T1-weighting in 3D fat
      suppressed spoiled gradient recalled echo (SPGR) imaging.
AB  - PURPOSE: To investigate the reversed intensity pattern in the laminar appearance
      of articular cartilage by 3D fat-suppressed spoiled gradient recalled echo (FS
      SPGR) imaging in magnetic resonance imaging (MRI). MATERIALS AND METHODS: The 3D
      SPGR experiments were carried out on canine articular cartilage with an echo time
      (TE) of 2.12 msec, a repetition time (TR) of 60 msec, and various flip angles (5
      degrees to 80 degrees ). In addition, T1, T2, and T2* in cartilage were imaged
      and used to explain the laminar appearance in SPGR imaging. RESULTS: The profiles
      of T2 and T2* in cartilage were similar in shape. However, the T2 values from the
      multigradient-echo imaging sequence were about 1/3 of those from single spin-echo
      sequences at a pixel resolution of 26 mum. While the laminar appearance of
      cartilage in spin-echo imaging is caused mostly by T2-weighting, the laminar
      appearance of cartilage in fast imaging (ie, short TR) at the magic angle can
      have a reversed intensity pattern, which is caused mostly by T1-weighting.
      CONCLUSION: The laminar appearance of articular cartilage can have opposite
      intensity patterns in the deep part of the tissue, depending on whether the image
      is T1-weighted or T2-weighted. The underlying molecular structure and
      experimental protocols should both be considered when one examines cartilage
      images in MRI.

PMID- 20815076
TI  - Feasibility of FAIR imaging for evaluating tumor perfusion.
AB  - PURPOSE: To evaluate the feasibility of flow-sensitive alternating inversion
      recovery (FAIR) for measuring blood flow in tumor models. MATERIALS AND METHODS:
      In eight mice tumor models, FAIR and dynamic contrast-enhanced magnetic resonance
      imaging (DCE-MRI) was performed. The reliability for measuring blood flow on FAIR
      was evaluated using the coefficient of variation of blood flow on psoas muscle.
      Three regions of interest (ROIs) were drawn in the peripheral, intermediate, and
      central portions within each tumor. The location of ROI was the same on FAIR and
      DCE-MR images. The correlation between the blood flow on FAIR and perfusion
      related parameters on DCE-MRI was evaluated using the Pearson correlation
      coefficient. RESULTS: The coefficient of variation for measuring blood flow was
      9.8%. Blood flow on FAIR showed a strong correlation with Kep (r = 0.77), percent
      relative enhancement (r = 0.73), and percent enhancement ratio (r = 0.81). The
      mean values of blood flow (mL/100 g/min) (358 vs. 207), Kep (sec(-) (1)) (7.46
      vs. 1.31), percent relative enhancement (179% vs. 134%), and percent enhancement
      ratio (42% vs. 26%) were greater in the peripheral portion than in the central
      portion (P < 0.01). CONCLUSION: As blood flow measurement on FAIR is reliable and
      closely related with that on DCE-MR, FAIR is feasible for measuring tumor blood
      flow.

PMID- 20815078
TI  - Pseudothrombocytopenia after changing insulin therapy in a case with insulin
      dependent diabetes mellitus: a first case report.

PMID- 20815077
TI  - T(2)-weighted 3D fast spin echo imaging with water-fat separation in a single
      acquisition.
AB  - PURPOSE: To develop a robust 3D fast spin echo (FSE) T(2)-weighted imaging method
      with uniform water and fat separation in a single acquisition, amenable to high
      quality multiplanar reformations. MATERIALS AND METHODS: The Iterative
      Decomposition of water and fat with Echo Asymmetry and Least squares estimation
      (IDEAL) method was integrated with modulated refocusing flip angle 3D-FSE. Echoes
      required for IDEAL processing were acquired by shifting the readout gradient with
      respect to the Carr-Purcell-Meiboom-Gill echo. To reduce the scan time, an
      alternative data acquisition using two gradient echoes per repetition was
      implemented. Using the latter approach, a total of four gradient echoes were
      acquired in two repetitions and used in the modified IDEAL reconstruction.
      RESULTS: 3D-FSE T(2)-weighted images with uniform water-fat separation were
      successfully acquired in various anatomies including breast, abdomen, knee, and
      ankle in clinically feasible scan times, ranging from 5:30-8:30 minutes. Using
      water-only and fat-only images, in-phase and out-of-phase images were
      reconstructed. CONCLUSION: 3D-FSE-IDEAL provides volumetric T(2)-weighted images
      with uniform water and fat separation in a single acquisition. High-resolution
      images with multiple contrasts can be reformatted to any orientation from a
      single acquisition. This could potentially replace 2D-FSE acquisitions with and
      without fat suppression and in multiple planes, thus improving overall imaging
      efficiency.

PMID- 20815079
TI  - Incidence of myelodysplastic syndromes within a nonprofit healthcare system in
      western Washington state, 2005-2006.
AB  - Myelodysplastic syndromes (MDS) incidence is unclear because of historical lack
      of population-based registration and possibly because of underdiagnosis. We
      conducted a study to evaluate completeness of MDS registration in the Seattle
      Puget Sound region of the Surveillance, Epidemiology, and End Results (SEER)
      program-which has reported the highest rates among the SEER registries since
      mandatory reporting of MDS began in 2001. We identified incident MDS cases of any
      age that occurred within a nonprofit healthcare system in western Washington
      State in 2005 or 2006 through the local SEER registry or by relevant diagnostic
      code followed by medical chart review to classify these patients as unlikely,
      possible, or definite/probable MDS. We calculated age-standardized incidence
      rates for all identified MDS cases and for case groups based on identification
      method, and we summarized medical histories of the MDS patients. MDS incidence in
      our study population was estimated as 7.0 per 100,000 person-years in 2005-2006
      when combining MDS cases identified by SEER and definite/probable cases
      identified by chart review, which was similar to the rate of 6.9 reported by our
      local SEER registry. The addition of possible MDS cases identified from chart
      review increased the rate to 10.2 per 100,000. MDS patients frequently had
      previous cancer diagnoses (25%) and comorbidities such as high blood pressure and
      diabetes. Our investigation suggests that although reporting of confirmed MDS
      diagnoses in our region appears complete, MDS incidence is likely underestimated
      because of omission of cases who are symptomatic but do not receive definitive
      diagnoses.

PMID- 20815080
TI  - Which steroids should we choose for the treatment of adult acute lymphoblastic
      leukemia?
AB  - Corticosteroids are essential and one of the mainstays in the treatment of acute
      lymphoblastic leukemia (ALL). In vitro assays show that dexamethasone(DXM) is
      five to six times more cytotoxic to leukemic lymphoblasts than prednisolone (PDN)
      [1], and the use of DXM as an alternative drug for PDN is an important issue in
      the treatment of childhood ALL. The current randomized comparisons in childhood
      ALL indicated a statistically significant and clinically important decrease in
      rate of isolated central nervous system (CNS) relapses and an increase in event
      free survival (EFS) with DXM. However, the data were limited in adult ALL.
      Recently, Labar et al. [2] reported their first investigation in comparison of
      the antileukemic activity and toxicity between DXM and PDN for adult patients
      with ALL and lymphoblastic lymphoma (LBL) through a randomized clinical trial
      (the ALL-4 trial of the EORTC Leukemia Group), and the author concluded that DXM
      as a steroid therapy for adult patients with ALL/LBL did not show any benefit
      compared with PDN, which did not support the experience from several other
      pediatric studies. In Labar's observation, about 70% of adult patients were high
      risk (HR) ALL. Most of the patients in pediatric trials were standard risk (SR)
      ALL. In our study, we also evaluate the role of DXM compared with PDN during
      induction or subsequent phases of therapy in adult ALL with emphasis on SR group.

PMID- 20815081
TI  - Understanding the terahertz spectra of crystalline pharmaceuticals: terahertz
      spectroscopy and solid-state density functional theory study of (S)-(+)-ibuprofen
      and (RS)-ibuprofen.
AB  - The potential applications of terahertz (THz) spectroscopy in the analysis of
      pharmaceutical products in their crystalline state have prompted the need for a
      more thorough understanding of the fundamental vibrational motions contributing
      to the THz spectra. The detection of variations in crystal structure and the
      reliable assignment of observed THz absorption features can be aided by the use
      of solid-state density functional theory (DFT). In this study, solid-state DFT
      with periodic boundary conditions was used to simulate the crystalline structure
      and assign the experimental THz spectra (10-90 cm(-1)) of the enantiomerically
      pure and racemic forms of the common pharmaceutical compound ibuprofen. The
      results clearly demonstrate the capabilities of DFT methodologies to accurately
      reproduce the THz spectra of large complicated molecular systems and provide
      insight into the internal and external vibrational motions that form the basis of
      THz spectroscopy.

PMID- 20815082
TI  - Theophylline-loaded compritol microspheres prepared by ultrasound-assisted
      atomization.
AB  - Nine solid dispersions were prepared by the melting method in the form of
      particles containing theophylline at 10%, 20%, and 30% (w/w) in three Compritols
      (Compritol 888 ATO, HD5 ATO, E ATO) to compare their efficiency in controlling
      theophylline release. After solidification the mass was ground and granules were
      evaluated by thermal [differential scanning calorimetry, hot stage microscopy
      (HSM)] and spectroscopic [Fourier transform infrared (FTIR), Raman, X-ray powder
      diffraction (XRD)] analysis and the solubility parameters. Another nine samples
      of the same composition were obtained as microspheres by ultrasound-assisted (US)
      atomization. XRD confirmed the presence of crystalline theophylline inside the
      solid dispersions. FTIR and Raman microspectroscopy revealed that crystals of the
      drug were present on the granule surface. On the contrary, the surface of the
      final microspheres did not present free drug crystals. The granules do not work
      so efficiently as microspheres in controlling the release of theophylline: 888
      ATO ~ HD5 ATO > E ATO represents the order of the ability of the Compritols to
      control the theophylline release from microspheres. HSM revealed that, on aging,
      the dissolved drug crystallizes, considerably modifying the granule formulation
      and that US vibration, speeding up the crystallization of the drug during the
      preparation of microspheres, greatly reduces the changes associated with aging.

PMID- 20815083
TI  - Single chain Fv fragment specific for human GM-CSF: selection and expression
      using a bacterial expression library.
AB  - Single chain antibodies (scFvs) are replacing whole antibody molecules since they
      are easy to produce on large scale and amenable to genetic modifications. Here we
      report the development of an anti-human granulocyte macrophage colony-stimulating
      factor (hGM-CSF) scFv as an immunoassay bio-reagent, utilizing an easily scalable
      bacterial expression system. For this, the V(H) and V(L) gene repertoires were
      amplified from the immunoglobulin complementary DNA, derived from total RNA of
      mice splenocytes, pre-sensitized with the antigen. The scFv library was expressed
      under the strong T7 promoter in BL21 (DE3) Escherichia coli cells. Preliminary
      screening led to the selection of four potential candidates, which were later
      subjected to light chain shuffling. Cross-reactivity analysis involving the
      original and shuffled candidates resulted in the selection of one scFv (scFv196)
      with no cross-reactivity against E. coli antigens. The binding affinity of the
      scFv196 for hGM-CSF, measured by surface plasmon resonance, was found to be
      within the physiological range (K(D) =1.5 MUM). The refolded scFv was also shown
      to recognize and bind the glycosylated antigen, a closer mimic of the
      physiological GM-CSF, potentiating its use in immunoassays. Expression studies
      using shake flasks suggested periplasmic export of the scFv196 protein.

PMID- 20815084
TI  - Phosphoglycerate mutase knock-out mutant Saccharomyces cerevisiae: physiological
      investigation and transcriptome analysis.
AB  - The yeast Saccharomyces cerevisiae is able to adapt its metabolism to grow on
      different carbon sources and to shift to non-fermentative growth on C2 or C3
      carbon sources (ethanol, acetate, or glycerol) through the activation of
      gluconeogenesis. Here, we studied the response to the deletion of the glycolytic
      and gluconeogenic gene GPM1, encoding for phosphoglycerate mutase. It was
      previously shown that a S. cerevisiae strain with non-functional copies of GPM1
      can only grow when glycerol and ethanol are both present as carbon sources,
      whilst addition of glucose was shown to strongly inhibit growth. It was suggested
      that glycerol is needed to feed gluconeogenesis whilst ethanol is required for
      respiration. Here, we studied the physiological response of the GPM1 knock-out
      mutant through fermentation and transcriptome analysis. Furthermore, we compared
      the physiological results with those obtained through simulations using a genome
      scale metabolic model, showing that glycerol is only needed in small amounts for
      growth. Our findings strongly suggest a severely impaired growth ability of the
      knock-out mutant, which presents increased transcript levels of genes involved in
      the pentose phosphate pathway and in the glyoxylate shunt. These results indicate
      an attempt to compensate for the energy imbalance caused by the deletion of the
      glycolytic/gluconeogenic gene within the mutant.

PMID- 20815085
TI  - Daunomycin interaction with DNA: microcalorimetric studies of the thermodynamics
      and binding mechanism.
AB  - Nucleic acids are an important target for many therapeutics. Small molecules that
      bind to nucleic acids are important in many aspects of medicines, particularly in
      cancer chemotherapy. In recent years, many studies have utilized polynucleic
      acids with various sequences to demonstrate the binding mechanism of daunomycin,
      a potent anticancer drug. This study describes that isothermal titration
      calorimetry is a useful tool for studying the fundamental binding mechanism
      systemically. The results suggest that the binding free energy is more favorable
      when the temperature is increased. The binding entropy contributes to this
      effect. Furthermore, the amine group on daunomycin contributes electrostatic
      interaction that induces the binding process. In addition, enthalpy-entropy
      compensation is also exhibited in the daunomycin-DNA binding mechanism. This
      study used an easy, convenient method of performing a systemic study in a
      recognition system. The results from this study provide additional information
      about microscopic mechanisms for molecular design and molecular recognition.

PMID- 20815086
TI  - Retention time prediction using the model of liquid chromatography of
      biomacromolecules at critical conditions in LC-MS phosphopeptide analysis.
AB  - LC combined with MS/MS analysis of complex mixtures of protein digests is a
      reliable and sensitive method for characterization of protein phosphorylation.
      Peptide retention times (RTs) measured during an LC-MS/MS run depend on both the
      peptide sequence and the location of modified amino acids. These RTs can be
      predicted using the LC of biomacromolecules at critical conditions model
      (BioLCCC). Comparing the observed RTs to those obtained from the BioLCCC model
      can provide additional validation of MS/MS-based peptide identifications to
      reduce the false discovery rate and to improve the reliability of phosphoproteome
      profiling. In this study, energies of interaction between phosphorylated residues
      and the surface of RP separation media for both "classic" alkyl C18 and polar
      embedded C18 stationary phases were experimentally determined and included in the
      BioLCCC model extended for phosphopeptide analysis. The RTs for phosphorylated
      peptides and their nonphosphorylated analogs were predicted using the extended
      BioLCCC model and compared with their experimental RTs. The extended model was
      evaluated using literary data and a complex phosphoproteome data set distributed
      through the Association of Biomolecular Resource Facilities Proteome Informatics
      Research Group 2010 study. The reported results demonstrate the capability of the
      extended BioLCCC model to predict RTs which may lead to improved sensitivity and
      reliability of LC-MS/MS-based phosphoproteome profiling.

PMID- 20815089
TI  - Why people hear voices.

PMID- 20815088
TI  - Proteomic analysis of testis biopsies in men treated with transient scrotal
      hyperthermia reveals the potential targets for contraceptive development.
AB  - Mild testicular heating safely and reversibly suppresses spermatogenesis. In this
      study, we attempted to clarify the underlying molecular mechanism(s) involved in
      heat-induced spermatogenesis suppression in human testis. We conducted global
      proteomic analyses of human testicular biopsies before, and at 2 and 9 wk after
      heat treatment. Thirty-one and Twenty-six known proteins were identified with
      significant differential expression at 2 and 9 wk after heat treatment,
      respectively. These were used to characterize the cellular and molecular events
      in the testes when seminiferous epithelia became damaged (2 wk) and recovered (9
      wk). At 2 wk post-treatment, the changed expression of a series of proteins could
      promote apoptosis or suppress proliferation and cell survival. At 9 wk post
      treatment, the changed expression of proteins mainly promoted cell proliferation,
      differentiation and survival, but resisted cell apoptosis. Among those heat
      regulated proteins, HNRNPH1 was selected for the further functional study. We
      found that HNRNPH1 was an anti-apoptosis protein that could regulate the
      expression of other heat-induced proteins. In conclusion, heat-induced reversible
      suppression of spermatogenesis occurred by modulating the expression of proteins
      related to proliferation, differentiation, apoptosis and cell survival pathways.
      These differentially expressed proteins were found to be key molecular targets
      affecting spermatogenesis after heat treatment.

PMID- 20815087
TI  - Characterization of the proteomes associating with three distinct membrane raft
      sub-types in murine sperm.
AB  - Mammalian sperm are transcriptionally and translationally inactive. To meet
      changing needs in the epididymis and female tract, they rely heavily on post
      translational modifications and protein acquisition/degradation. Membrane rafts
      are sterol and sphingolipid-enriched micro-domains that organize and regulate
      various pathways. Rafts have significance in sperm by transducing the stimulus of
      sterol efflux into changes in intracellular signaling that confer fertilization
      competence. We recently characterized three biochemically distinct sub-types of
      sperm rafts, and now present profiles for proteins targeting to and associating
      with these sub-types, along with a fraction largely comprised of "non-raft"
      domains. Proteomics analysis using a gel-based LC-MS/MS approach identified 190
      strictly validated proteins in the raft sub-types. Interestingly, many of these
      are known to be expressed in the epididymis, where sperm membrane composition
      matures. To investigate potential roles for rafts in epididymal protein
      acquisition, we compared the expression and localization of two different sterol
      interacting proteins, apolipoprotein-A1 (apoA1) and prominin-1 (prom1) in sperm
      from different zones. We found that apoA1 was gradually added to the plasma
      membrane overlying the acrosome, whereas prom1 was not, suggesting different
      mechanisms for raft protein acquisition. Our results define raft-associating
      proteins, demonstrate functional similarities and differences among raft sub
      types, and provide insights into raft-mediated epididymal protein acquisition.

PMID- 20815090
TI  - Generic ARBs are coming.

PMID- 20815091
TI  - Ask the doctor. After I had and abnormal electrocardiogram,my doctor wants me to
      have a nuclear stress test to check my arteries for any blockages. (I also have a
      left side bundle block.) What noninvasive test would give as much information (or
      almost as much) as a nuclear stress test? I have had many scans, for this and
      that, so I would like to limit my exposure to radiation if possible.

PMID- 20815092
TI  - Meta-analysis confirms relationship between eGFR, albuminuria and risk of
      mortality.

PMID- 20815093
TI  - Hypertension development in normotensive adolescents.

PMID- 20815095
TI  - Serial speckle tracking and successful post-STEMI percutaneous coronary
      intervention: incremental value versus visual wall motion analysis.
AB  - The present clinical case shows that assessment of longitudinal strain in the
      coronary care unit using speckle tracking echocardiography can help to quantify
      myocardial damage in the context of acute coronary syndromes and detect changes
      otherwise not visible with semi-quantitative evaluation of wall motion.

PMID- 20815094
TI  - Sensitivity of urinary mesothelin in patients with malignant mesothelioma.
AB  - INTRODUCTION: Malignant mesothelioma (MM) is an aggressive, uniformly fatal tumor
      usually caused by exposure to asbestos. Soluble mesothelin has been intensively
      investigated in the serum as a biomarker for this disease. As urine is less
      complex and less invasive to collect than serum and may be a more acceptable
      specimen for large-scale screening studies of asbestos-exposed individuals, we
      determined whether the sensitivity and specificity for MM could be improved by
      measuring soluble mesothelin in the urine. METHODS: Soluble mesothelin
      concentrations were determined using the MESOMARK assay in concurrent serum and
      urine samples from 70 patients with pleural MM, 111 patients with asbestos
      related lung or pleural disease, and 45 patients with benign nonasbestos-related
      lung and pleural disease. Only patients with serum creatinine levels within the
      normal range were included in the study. Sensitivities were determined and
      receiver operator characteristic curves were generated to compare the diagnostic
      accuracy of mesothelin in the serum and urine. RESULTS: At a specificity of 95%
      relative to individuals with benign lung or pleural disease, serum mesothelin had
      a sensitivity of 66% and area under the curve of 0.882, whereas urinary
      mesothelin corrected for urine creatinine concentration had a sensitivity of 53%
      and area under the curve of 0.787. CONCLUSIONS: The sensitivity of urinary
      mesothelin does not warrant the use of urine as a biomarker specimen for MM
      diagnosis.

PMID- 20815096
TI  - Comparison of central corneal thickness measurements using Pentacam and
      ultrasonic pachymetry in post-LASIK eyes for myopia.
AB  - PURPOSE: To compare central corneal thickness (CCT) measurements obtained using
      the Pentacam Scheimpflug system with those obtained using DGH ultrasound
      pachymetry (UP) in post-laser in situ keratomileusis (LASIK) eyes for myopia.
      METHODS: In a prospective study, measurement agreement was assessed in 143 eyes
      of 72 post-LASIK patients using both the Pentacam and UP at the Eye Consultants
      Center in Riyadh, Saudi Arabia. RESULTS: The mean CCT was 522 +/- 42.2 microm
      with the Oculus Pentacam and 516.2 +/- 40.6 microm with UP. The Bland-Altman plot
      showed that the mean +/- SD for the differences between the 2 devices was 5.8 +/-
      13.6 microm, with 95% confidence interval limits ranging from -20.9 microm to
      32.6 microm. A test of statistical significance indicated that the mean
      differences of 5.8 +/- 13.6 microm differed significantly from zero (p<0.001;
      Wilcoxon signed-rank test), thus indicating that the Pentacam measurements tended
      to overestimate CCT compared with UP. Analysis of regression showed a high
      correlation between the values obtained with both devices (r=0.947, p<0.001).
      CONCLUSIONS: In post-LASIK myopic eyes, although a high correlation has been
      shown between Pentacam and UP measurements, Pentacam tends to overestimate CCT
      compared to UP. Pentacam probably cannot be used interchangeably with UP in post
      LASIK eyes for myopia.

PMID- 20815097
TI  - Gerard Fleer: straightforward on random walks.

PMID- 20815098
TI  - Climacteric commentaries. Should we kill them all?

PMID- 20815099
TI  - Climacteric commentaries. Women's Health Initiative, osteoporosis prescribing and
      fracture incidence.

PMID- 20815101
TI  - Climacteric commentaries. Symptoms of depression among pre-, peri- and
      postmenopausal women in Turkey.

PMID- 20815100
TI  - Climacteric commentaries. Endogenous estradiol and coronary calcifications in
      postmenopausal women.

PMID- 20815102
TI  - Climacteric commentaries. The search for an effective non-hormonal treatment for
      hot flushes continues.

PMID- 20815103
TI  - Climacteric commentaries. The fragile-bone dispute.

PMID- 20815104
TI  - What to advise patients about hernias.

PMID- 20815105
TI  - [Abstracts of the IV Congress of Epidemiology and the XVI Current Events of
      Pharo, organized by the Association of French Language Epidemiologists and the
      Association for the Development of Epidemiology. September 15-17, 2010.
      Marseille, France].

PMID- 20815106
TI  - A course in basic surgical techniques improves medical student confidence in key
      skills.

PMID- 20815107
TI  - Web-based training package for HEEADSSS assessment and motivational interviewing
      techniques: a multi-professional evaluation survey.

PMID- 20815109
TI  - [Reimbursement for certificates?].

PMID- 20815108
TI  - Trial results finally show potential for microbicidal HIV gel.

PMID- 20815110
TI  - Atorvastatin for reduction of myocardial damage during angioplasty trials.

PMID- 20815111
TI  - Comments on the article "Reintroducing the Tzanck Smear".

PMID- 20815112
TI  - The real cost of counterfeit medicines.

PMID- 20815113
TI  - Mechanism of dissociation of human apolipoproteins A-I, A-11, and C from
      complexes with dimyristoylphosphatidylcholine as studied by thermal denaturation.
AB  - The effect of temperature on the structure of human apolipoprotein A-I (apo A-I),
      apo A-11, and the combined apo C fraction in the absence and presence of
      dimyristoylphosphatidylcholine(DMPC) has been investigated.The thermal
      denaturation of the apolipoproteins was monitored by circular dichroism
      spectroscopy. In the absence of lipid,the apolipoproteins A-I and A-I1 denature
      over a wide temperature range, giving van't Hoff enthalpies of 33 +/- 4 kcal/mol
      of apo A-I and 17.8 +/- 0.2 kcal/mol of apo A-11. These enthalpies are
      independent of the protein concentration, although a decrease in molar
      ellipticity was observed on increasing the protein concentration from 0.01 to 1
      mg/mL. No effect of temperature could be observed on the combined apoC fraction
      because at 0.01 and 1 mg/mL the apo C's were essentially random coiled. In the
      presence of DMPC, thermal denaturation could be measured for apo A-I above 70-75
      "C and for apo A-I1 and apo C above about 45 OC. In general,the denaturations
      were biphasic reactions for all apolipoproteins tested, with only a third, minor
      intermediate phase for apo A-I/DMPC denaturation. The two major kinetic phases
      are identified as an unfolding reaction of the apolipoprotein bound to the
      complex followed by a desorption step.The relaxation times (tau) associated with
      the latter step are dependent on the molecular weight of the apoprotein: when the
      temperature is increased from 70 to 90 OC, tau decreases from 400 to 1 min for
      apo A-I, while for apo A-I1 and apoC as the temperature is increased from 50 to
      70 OC, tau decreases from 15 to l min. The activation energies for the desorption
      of apoprotein decrease with decreasing molecular weight: the values are 71 +/- 2
      kcal/mol of apo A-I, 28 +/- 3 kcal/mol of apo A-11, and 22 +/- 3 kcal/mol of apo
      C. The thermal denaturation of apo A-I/DMPC is a thermodynamically irreversible
      process whereas the denaturations of apoA-II/DMPC and apo C/DMPC complexes are
      reversible with midpoints of 71 and 54 "C, respectively. The van't Hoff
      enthalpies are 16.8 +/- 0.6 kcal/mol of apo A-I1 (T < 70 "C),86 +/- 2 kcal/mol of
      apo A-I1 (T > 70 "C), and 22.3 +/- 0.8 kcal/mol of apo C. On the basis of the
      above findings, a model to describe the association and dissociation of
      apolipoproteins with DMPC has been derived. It is assumed that, on a molecular
      level, the association reaction is determined by two parameters: (1) the
      intrinsic rate constant describing the insertion of an apolipoprotein into a
      "vacancy" in the phospholipid matrix ("on rate") and (2) the probability of the
      colliding apoprotein molecule encountering a vacancy in the phospholipid bilayer.
      Alterations in either of these two parameters change the macroscopic rate
      constant of association.Desorption ("off rate") involves the protein leaving from
      a constant phospholipid environment because the perturbed adjacent lipid
      molecules render this process insensitive to the physical state of the remainder
      of the bilayer. The similarities in the van't Hoff enthalpies associated with the
      reversible desorption of apo A-I1 and apo C to literature values for the
      calorimetric enthalpies of association of these proteins with DMPC suggest that
      the desorption is a two-state process.

PMID- 20815114
TI  - Dominance of women in veterinary science.

PMID- 20815115
TI  - Re: Sheba - an ethical dilemma.

PMID- 20815116
TI  - Variant mitoses in lower eukaryotes: indicators of the evolution of mitosis.

PMID- 20815117
TI  - The centriolar complex.

PMID- 20815118
TI  - The structural organization of mammalian retinal disc membrane.

PMID- 20815119
TI  - The roles of transport and phosphorylation in nutrient uptake in cultured animal
      cells.

PMID- 20815120
TI  - The contractile apparatus of smooth muscle.

PMID- 20815121
TI  - Cytophysiology of the adrenal zona glomerulosa.

PMID- 20815122
TI  - A collective remembrance of George Clinton Andrews, Jr (1891-1978).

PMID- 20815123
TI  - [Respiratory health and the National Institute of Respiratory Diseases].

PMID- 20815124
TI  - [Is a calcineurin inhibitor required as part of the immunosuppression scheme in
      kidney transplant recipients that share 2-haplotypes with their donors?].
AB  - INTRODUCTION: The recipients of HLA-identical live-donors grafts (RKT 2HP) have a
      low immunologic risk, and it is common to use immunosuppressive regimen with two
      medicaments excluding the calcineurin inhibitor. This study compares the long
      term outcomes of the double immunosuppressive therapy versus the triple therapy
      in RKT 2HP. MATERIALS AND METHODS: This study is a retrolective cohort. The
      patients were divided in two groups: (1) RKT 2HP who receive double
      immunosupresive therapy and (2) RKT 2HP with triple immunosupresive therapy. The
      outcomes evaluated were: renal function, acute rejection rate, lost of renal
      allograft, death rate, infections and hospitalization, change in the
      immunosupresive therapy and its causes. RESULTS: We analyzed 85 kidney transplant
      recipients who share two haplotypes, 60 in the group 1 and 25 in the group 2. The
      median of time of follow-up in the group 1 was 138 months (min 23 and max 302)
      and 55 months (min 12 and max 106) in the group 2. There were four cellular acute
      rejection and nine allograft lost in patients of the group 1. There wasn't any
      significant difference between the allograft outcome and the renal function at 60
      months of follow out between the groups. 23 patients had change in the
      immunosuppressive therapy, 12 (53%) in the group 1 and 11 (47%) in the group 2.
      The major cause of change of therapy in the group 1 was leucopenia by azatioprin
      (five patients); and in the group 2 was nephrotoxicity for calcineurin inhibitor
      (six patients). DISCUSSION: Despite the evident nephrotoxicity, the use of
      calcineurin inhibitor is useful even in patients with low immunologic risk.
      According to the time of follow-up between the groups, even when the allograft
      survival was superior in group 2, the difference wasn't significative, it might
      be because the lower number of patients in group 1.

PMID- 20815125
TI  - [Epidemiologic study on dental caries and treatment needs in schoolchildren aged
      six to twelve years from San Luis Potosi].
AB  - OBJECTIVE: To determine the experience, prevalence and severity of dental caries,
      as well as the Significant Caries Index (SiC) and the treatment needs (TN) in
      schoolchildren aged six to twelve years. Equally, to estimate the effect of
      caries in primary dentition on caries in permanent dentition. MATERIAL AND
      METHODS: A cross-sectional study was realized in 3865 schoolchildren from San
      Luis Potosi City, Mexico. Subjects were clinically evaluated by three
      standardized examiners (kappa > 0.85). For detection of caries was employed the
      WHO's criteria for primary (dmft) and permanent (DMFT) dentitions. In the
      statistical analyzes non-parametric test and logistic regression were used.
      RESULTS: Mean of age was 8.69 +/- 1.79 and 51.3% were women. In the primary
      dentition: dmft index was 1.88 +/- 2.34 and the caries prevalence (dmft >0) of
      56.8%. In account to severity 22.0% and 5.6% have dmft >3 and dmft >6,
      respectively. In children of six years, the caries prevalence was 56.0% and the
      SiC of 5.45. In the permanent dentition: DMFT index was 1.11 +/- 2.03 and the
      caries prevalence (DMFT >0) of 36.8%. In account to severity 11.8% and 2.8% have
      DMFT >3 and DMFT >6, respectively. In children of twelve years, the DMFT index
      caries 4.14 +/- 4.15 and the SiC of 9.15. The TN index was of 88.5% for primary
      dentition and 93.6% for the permanent. In logistic regression we observed
      associated to caries prevalence in permanent dentition; presence of caries in
      primary dentition (OR = 6.37; p < 0.001), female sex (OR = 1.33; p < 0.001) and
      higher age (OR = 1.69; p < 0.001). CONCLUSIONS: Caries prevalence to six years
      old and DMFT index to twelve years old were highest to values established by WHO.
      Caries severity in the primary dentition was two times than observed in the
      permanent dentition. High TN in both dentitions was observed. Presence of caries
      in primary dentition was a strong risk indicator for to present caries in
      permanent dentition.

PMID- 20815126
TI  - Right and left partial iatrogenic injuries of the biliary tree. Therapeutic
      options.
AB  - BACKGROUND: Bile duct injuries (BDI) have a wide array of presentation. Left
      partial injuries (Strasberg D) of the hepatic duct are the result of excessive
      traction, which dissects the hepatic hilum and provokes medial perforations
      without continuity loss. Right partial injuries (Strasberg A, B and C) are
      produced by direct damage to the hepatic duct or isolated injury to the right and
      accessory ducts. It is important to determine frequency, spectrum and treatment
      outcome of this BDI in the surgical scenario. METHODS: Patients with BDI who
      underwent surgical treatment in our hospital were reviewed, right and left
      partial injuries were selected. Demographic, clinical and therapeutic data were
      analyzed. RESULTS: In a 16-year period, 405 patients underwent surgical treatment
      of BDI. 31 (8%) were classified as a left partial injury (Strasberg D): 23
      injuries at the common hepatic duct treated with a Hepatojejunostomy (HJ); four
      at the confluence level which received a HJ with neoconfluence construction; two
      partial injuries in the left hepatic duct underwent a selective left HJ; and two
      complete occlusions of the left hepatic duct, one treated with a partial
      hepatectomy and the last case underwent a partial HJ. Right partial injuries
      (Strasberg A, B or C) were identified in 21 cases (5%), their treatment was
      tailored according to the type of BDI (conservative, selective HJ, or
      hepatectomy). CONCLUSIONS: In our series the frequency of left and right partial
      BDI injuries was 8% and 5%, respectively. The spectrum of analyzed injuries
      included four subtypes for the left partial and eight for the right partial
      lesions. Most BDI in the two analyzed groups presented concomitant
      devascularization of the extra-hepatic ducts, therefore receiving surgical
      treatment rather than endoscopic treatment was done.

PMID- 20815127
TI  - [Experimental model of canine oleic acid-induced acute lung injury: establishment
      of a working model].
AB  - INTRODUCTION: There are several experimental model of acute lung injury induced
      by oleic acid (OA); however, there are few studies that show how this injury
      develops. OBJECTIVE: This study seeks to detail the x-ray, hemodynamic,
      gasometrical, gravimetrical, macroscopic and microscopic alterations developed in
      an experimental model of canine OA-induced acute lung injury (ALI). MATERIAL AND
      METHODS: Twelve dogs were divided in 2 study groups: Group I (n=6): Control group
      without ALI. Group II (n=6); OA-induced ALI. All dogs were submitted to X-ray,
      hemodynamic and gasometric evaluation before ALI induction, and later every 15
      minutes during 150 minutes. At the end of the study, the animals were
      euthanatized and were evaluated the changes gravimetric, macroscopic and
      microscopic in injured lungs. RESULTS: All the animals survived through the
      study. In group II, 100% of the animals developed x-ray (p < 0.003 Wilcoxon),
      hemodynamic, gasometrical and gravimetric (p < 0.5 ANOVA, Tukey), macroscopically
      and microscopically (p < 0.001 Wilcoxon) ALI. CONCLUSIONS: The OA-induced ALI is
      a model in which dogs develop X-ray, hemodynamic, gasometrical, gravimetrical,
      macroscopically and microscopically injuries of the exudative phase that lung
      with ALI injury presents.

PMID- 20815128
TI  - [Optic neuritis in systemic lupus erythematosus: report of 12 cases].
AB  - OBJECTIVE: To review the cases of optic neuritis in the population of patients
      with Systemic Lupus Erythematosus (SLE) who attends to the Instituto Nacional de
      Ciencias Medicas y Nutricion Salvador Zubiran. MATERIAL AND METHODS: We included
      12 patients with optic neuritis who fulfilled the ACR SLE criteria. Age, gender,
      previous treatment, unilateral or bilateral involvement, recurrence, other
      concomitant neurologic symptoms, SLE activity, anticardiolipin antibodies and
      visual outcome were recorded. RESULTS: The female:male ratio was 5:1. The mean
      age of the study group was 33 +/- 13 years. In two patients the optic neuritis
      antedated the SLE diagnosis, in one the event presented at the same time of lupus
      onset, and in the rest of the patients the optic neuritis postdated the diagnosis
      of SLE. The median SLE duration was three years (1-12). At the optic neuritis
      onset, four of the patients also presented other lupus manifestations whereas the
      rest of them were in remission. The event was bilateral in 33% and recurrent in
      three patients (median two events 2-6). In three cases an event of transverse
      myelitis was also documented. Only one of the patients had an established
      diagnosis of antiphospholipid syndrome, however eight were positive for
      anticardiolipin antibodies. Besides treatment with steroids and in two cases with
      cyclophosphamide, five of the patients had blindness and only four regained
      normal visual acuity. CONCLUSION: Although optic neuritis is a rare manifestation
      in SLE patients, it is a cause of blindness.

PMID- 20815129
TI  - [Adherence to a medical nutrition therapy program in pregnant women with
      diabetes, measured by three methods, and its association with glycemic control].
AB  - INTRODUCTION: The measurement of adherence to nutrition therapy is essential to
      evaluate if the outcomes are related to given recommendations. MATERIAL AND
      METHODS: The aim of this study was to describe adherence to a Medical Nutrition
      Therapy Program in Mexican pregnant women with diabetes, using three different
      methods; and evaluate its association with glycemic control. Adherence was
      measured with a questionnaire (0-100%), women's self-perception (0-100%) and
      energy intake adequacy by multiple pass 24 hour recall (85-115% of
      recommendation). Women were randomly assigned to two different dietary
      strategies. Glycemic control was determined by capillary glucose self-monitoring.
      RESULTS: Women analyzed in this study (n=69) had an age range of 22-42 years;
      47.8% had type 2 diabetes (DM2) and 52.2% had gestational diabetes (GDM). Energy
      intake adequacy was higher in women with GDM (41.9% vs. 37.7%, p = 0.001).
      Average adherence measured with the questionnaire was 55%; no differences were
      found by type of diabetes. Self-perception was higher in women with DM2 (84%)
      when compared to women with GDM (70%) (p = 0.039). No differences were found in
      the three methods by study group. Optimal glycemic control was observed in 50% of
      women; no association was found with adherence measured with any of the three
      methods studied. CONCLUSIONS: The observed differences in adherences suggest that
      it may be recommendable to combine different measurement methods and include
      social and psychological factors that affect behavioral change.

PMID- 20815130
TI  - [Prevalence and associated factors to allergic rhinitis in school children of
      ciudad Guzman, Mexico].
AB  - INTRODUCTION: A considerable amount of risk factors have been proposed to explain
      the increase in the frequency of allergic rhinitis; some of them are atopy,
      cigarette smoking of parents, birthweight, type of feeding at the time of birth
      and the nutritional state, but the results have been inconsistent. The present
      study seeks to investigate the role played by these risk factors in the
      development of allergic rhinitis in a sample of school children. MATERIAL AND
      METHODS: The data was gathered from 6-12 year old school children. Their parents
      filled out the questionary which was validated by means of the International
      Study on Asthma and Allergies in Childhood. Further questioning included
      background regarding atopy, breastfeeding, birthweight and type of delivery;
      weight and height were used to calculate the body mass index. RESULTS: Among 740
      children in this study, the frequency of allergic rhinitis was 5.5%; the past
      history of allergic disease in the father (OR = 3.1; CI 95%, 1.2-8.1, p = 0.018)
      or in the mother (OR = 3.2; CI 95%, 1.5-6.6, p = 0.002) was importantly
      associated to the development of allergic rhinitis. We did not find association
      with the rest of the variables under study. CONCLUSION: These results indicate
      that the prevalence of allergic rhinitis is similar to the one reported in
      previous studies. The only risk factor associated to allergic rhinitis was the
      past history of atopic disease in their parents.

PMID- 20815131
TI  - [The two leading hypothesis regarding the molecular mechanisms and etiology of
      preeclampsia, and the Mexican experience in the world context].
AB  - Preeclampsia (PE) is one of the most severe complications of pregnancy. PE is
      responsible for the highest rates of morbidity and mortality for both pregnant
      women and the neonate. In this review, we first address general aspects of PE and
      its diagnosis, along with some epidemiological aspects of this disease in the
      mexican population, in particular the experience from the Instituto Mexicano del
      Seguro Social. Even though over the last 20 years a great deal of evidence has
      accumulated regarding PE's pathophysiology, an exact mechanism to explain its
      etiology has not been established. This review aims to cover the status of two of
      the most important hypotheses in the etiology of PE: the immunological and the
      placental ischemia hypotheses. Recent data suggest that Natural Killer cells (NK)
      play a major role in the decidual spiral arteriole remodeling and in normal
      placental development. In genetic studies, KIR receptors present in NK cells have
      been involved in the susceptibility for the disease. In this review, we discuss
      data of our group regarding the presence of NK cells in the decidua, at the end
      of pregnancy and the genotypes of KIR receptors in normal and preeclamptic
      Mexican population. PE is characterized by abnormal placentation and hypoxia with
      an increase of anti-angiogenic factors; the Hypoxia-inducible factor 1-alfa (HIF1
      alfa) is over expressed in PE. In this review, we also included some of our
      results concerning the polymorphisms and regulation of HIF in preeclamptic women.

PMID- 20815132
TI  - [Hypertrophic ostearthropathy: causes, lineage and texture].

PMID- 20815133
TI  - [Biology and biochemical aspects of long-chains polyunsaturated fatty acid during
      gestation].
AB  - During pregnancy, the mother must provide the nutrients necessary for proper
      differentiation, maturation and growth of fetal organs and systems. During this
      period, the mother adapts her metabolism to address the continuing demand for
      substrates to be transferred to the fetus through the placenta. Essential fatty
      acids cannot be synthesized by humans, therefore, should be consumed as part of
      the diet. Its derivates, long-chain polyunsaturated fatty acids (LC-PUFAs) from
      biosynthesis in the maternal liver during pregnancy and lactation are compounds
      that will form part of the cell membranes of the brain, retina, and liver, fetal
      and newborn heart, thereby enabling the smooth, activation and regulation of
      cellular functions. Therefore, adequate nutritional status of the mother during
      pregnancy and lactation is necessary to ensure adequate product development. This
      article aims to review some aspects of the adaptive mechanisms of maternal lipid
      metabolism, mainly from LC-PUFAs compensating energy expenditure and allow the
      proper development of the product.

PMID- 20815134
TI  - Strategy to establish a cut-off point for hyperinsulinemia.

PMID- 20815135
TI  - [Thrombosis of double inferior vena cava with a thrombosis-in-transit and
      insertion of two filters].

PMID- 20815136
TI  - Infant mortality statistics from the 2006 period linked birth/infant death data
      set.
AB  - OBJECTIVES: This report presents 2006 period infant mortality statistics from the
      linked birth/infant death data set (linked file) by a variety of maternal and
      infant characteristics. The linked file differs from the mortality file, which is
      based entirely on death certificate data. METHODS: Descriptive tabulations of
      data are presented and interpreted. RESULTS: The U.S. infant mortality rate was
      6.68 infant deaths per 1,000 live births in 2006, a 3 percent decline from 6.86
      in 2005. Infant mortality rates ranged from 4.52 per 1,000 live births for
      Central and South American mothers to 13.35 for non-Hispanic black mothers.
      Infant mortality rates were higher for those infants whose mothers were born in
      the 50 states or the District of Columbia, were unmarried, or were born in
      multiple deliveries. Infant mortality was also higher for male infants and
      infants born preterm or at low birthweight. The neonatal mortality rate was
      essentially unchanged in 2006 (4.46) from 2005 (4.54). The postneonatal mortality
      rate decreased 4 percent, from 2.32 in 2005 to 2.22 in 2006. Infants born at the
      lowest gestational ages and birthweights have a large impact on overall U.S.
      infant mortality. For example, more than half of all infant deaths in the United
      States in 2006 (54 percent) occurred to the 2 percent of infants born very
      preterm (less than 32 weeks of gestation). Still, infant mortality rates for late
      preterm infants (34-36 weeks of gestation) were three times those for term
      infants (37-41 weeks). The three leading causes of infant death--congenital
      malformations, low birthweight, and sudden infant death syndrome--taken together
      accounted for 46 percent of all infant deaths. The percentage of infant deaths
      that were "preterm-related" was 36.1 percent in 2006. The preterm-related infant
      mortality rate for non-Hispanic black mothers was 3.4 times higher and the rate
      for Puerto Rican mothers was 84 percent higher than for non-Hispanic white
      mothers.

PMID- 20815137
TI  - Genome-wide functional annotation by integrating multiple microarray datasets
      using meta-analysis.
AB  - Tremendous amounts of microarray data for various organisms have provided a rich
      opportunity for computational analyses of gene products. Integrating these data
      can help inferring biological knowledge effectively. We present a new statistical
      method of integrating multiple microarray datasets for gene function prediction.
      We tested the performance of our model using yeast and human datasets. Our
      results show that combining multiple datasets improves the accuracy over the best
      function prediction of any single dataset significantly. We also compared
      performance of the meta p-value and meta correlation methods for function
      prediction. Supplementary results and code are available at
      http://digbio.missouri.edu/metaanalyses.

PMID- 20815138
TI  - Synthetic gene design with a large number of hidden stops.
AB  - Hidden stops are nucleotide triples TAA, TAG and TGA that appear on the second
      and third reading frames of a protein coding gene. Recent studies suggested the
      important role of hidden stops in preventing misread of mRNA. We study the
      problem of designing protein-encoding genes with large number of hidden stops
      under several biological constraints. With simple constraints, redesigned genes
      have provable maximal number of hidden stops. With more complex constraints,
      redesigned genes still have many more hidden stops than wild-type genes. We
      showed that redesigned genes have a distinct positional advantage in assisting
      early termination of frame-shifts.

PMID- 20815139
TI  - Detecting duplicate biological entities using Shortest Path Edit Distance.
AB  - Duplicate entity detection in biological data is an important research task. In
      this paper, we propose a novel and context-sensitive Shortest Path Edit Distance
      (SPED) extending and supplementing our previous work on Markov Random Field-based
      Edit Distance (MRFED). SPED transforms the edit distance computational problem to
      the calculation of the shortest path among two selected vertices of a graph. We
      produce several modifications of SPED by applying Levenshtein, arithmetic mean,
      histogram difference and TFIDF techniques to solve subtasks. We compare SPED
      performance to other well-known distance algorithms for biological entity
      matching. The experimental results show that SPED produces competitive outcomes.

PMID- 20815140
TI  - Prediction of alternatively spliced exons using support vector machines.
AB  - Alternative splicing is a mechanism for generating different gene transcripts
      (called isoforms) from the same genomic sequence. In this paper, we explore the
      predictive power of a large set of diverse gene features that have been
      experimentally shown to have effect on alternative splicing. We use such features
      to build support vector machine classifiers for predicting alternatively spliced
      exons. Experimental results show that classifiers built from the diverse set of
      features give better results than those that consider only basic sequence
      features. Furthermore, we use feature selection methods to identify the most
      informative features for the prediction problem at hand.

PMID- 20815141
TI  - A data mining approach to dinoflagellate clustering according to sterol
      composition: correlations with evolutionary history.
AB  - This study examined the sterol compositions of 102 dinoflagellates using
      clustering and cluster validation techniques, as a means of determining the
      relatedness of the organisms. In addition, dinoflagellate sterol-based
      relationships were compared statistically to 18S rDNA-based phylogenetic
      relationships using the Mantel test. Our results indicated that the examined
      dinoflagellates formed six clusters based on sterol composition and that several,
      but not all, dinoflagellate genera, which formed discrete clusters in the 18S
      rDNA-based phylogeny, shared similar sterol compositions. This and other
      correspondences suggest that the sterol compositions of dinoflagellates are
      explained, to a certain extent, by the evolutionary history of this lineage.

PMID- 20815142
TI  - Towards site-based protein functional annotations.
AB  - The exact relationship between protein active centres and protein functions is
      unclear even after decades of intensive study. To improve functional prediction
      ability based on the local structures, we proposed three different methods. 1. We
      used Markov Random Field (MRF) to describe protein active region. 2. We developed
      filtering method that considers the local environment around the active sites. 3.
      We created multiple structure motifs by extending the motif to neighbouring
      residues. Our experiment results with enzyme families < 40% sequence identity
      demonstrated that our methods reduced random matches and could improve up to 70%
      of the functional annotation ability (using area under curve).

PMID- 20815143
TI  - Robust QTL analysis by minimum beta-divergence method.
AB  - Robustness has received too little attention in Quantitative Trait Loci (QTL)
      analysis in experimental crosses. This paper discusses a robust QTL mapping
      algorithm based on Composite Interval Mapping (CIM) model by minimising beta
      divergence using the EM like algorithm. We investigate the robustness performance
      of the proposed method in a comparison of Interval Mapping (IM) and CIM
      algorithms using both synthetic and real datasets. Experimental results show that
      the proposed method significantly improves the performance over the traditional
      IM and CIM methods for QTL analysis in presence of outliers; otherwise, it keeps
      equal performance.

PMID- 20815144
TI  - [Present situation of crime in Japan].
AB  - Recently, it has been said that public safety has changed for the worse in Japan.
      After a peak in 1994, the total number of crimes gradually decreased, but it
      still remains at a higher level when compared to that in 1989. In addition to the
      persistent increase in the number of child abuse and drug abuse/dependence cases
      as well as stalking, indiscriminate crime by an unknown assailant is now
      increasing in Japan, particularly this year. The present criminal tendency seems
      to be based on the rapid change from an equal to unequal societal status, the
      ease of access to personal computers/the Internet, and the increase of crime
      committed by foreigners.

PMID- 20815145
TI  - [Death inquiry system in Japan].
AB  - In Japan, there are two different systems of death investigation: criminal
      inspection and judicial autopsy from a criminal justice standpoint and, from a
      public health standpoint, administrative inspection and either autopsy on consent
      or administrative one. As a result, reason for the death inquiry is often
      obscure. One aim of death inquiry is to prevent any future loss of life under
      similar circumstances, which the Japanese system does not consider. The
      systematic reform of the Japanese death inquiry system is thought to be
      necessary.

PMID- 20815146
TI  - [Occupational poisoning and biological exposure monitoring].
AB  - Biological exposure monitoring is available for detecting occupational toxic
      chemicals. It is possible to evaluate the exposure and adverse effects induced
      such the occupational toxic chemicals with biological exposure monitoring. It is
      used in health examination, for the recommendation of occupational exposure
      limits based on biological exposure monitoring, and for biological exposure
      indices of the American Conference of Governmental Industrial Hygienists (ACGIH).

PMID- 20815147
TI  - [Suicide due to carbon monoxide poisoning-trends and preventive measures].
AB  - To lessen the number of suicide is a nationwide problem in Japan. Recently,
      suicide due to carbon monoxide poisoning with charcoal burning is increased. The
      information on this method seems to have spread via suicide-related websites. In
      addition, there are concerns about drugs and illegal substances that can be
      bought obtained via the internet. In Japan, the establishment of a voluntary
      internet guideline in 2005 was effective to save the lives of the persons with
      suicidal ideations.

PMID- 20815148
TI  - [Roles of pathological autopsy for analyzing causes of death].
AB  - The system for death certification is essential for maintaining the nation's
      safety. The rate of performing autopsy in Japan is the lowest among the developed
      countries. One of the reasons is the serious shortage of both anatomical and
      forensic pathologists, just 2000 and 120 personnel in number, respectively. In
      order to overcome the present insufficiency, Japan needs not only to establish
      new laws for death certification, but also to revise the present medical
      residency system for the training of autopsy-performing medical doctors.

PMID- 20815149
TI  - [Death investigation and postmortem imaging].
AB  - Our department has employed postmortem computed tomography (CT) for the last 4
      years. When CT is combined with autopsy, it is very helpful. However, there are
      some demerits. CT cannot identify death due to intoxication. In only about 30% of
      cases can CT determine the cause of death. CT sometimes overlooks injuries such
      as cervical spinal injury. If a doctor is to determine the cause of death only
      from CT and not report the case to the police, which can provide information
      about the scene or personal history, even a homicide may be mistaken as a disease
      related death. Without reforms of the death investigation system, the budget for
      postmortem CT cannot be relied upon. To employ postmortem CT efficiently, reform
      of the death investigation system is necessary.

PMID- 20815150
TI  - [DNA examination for criminal investigation].
AB  - The main purpose of DNA examination in a criminal investigation is identification
      from biological specimen material (sample). Occasionally, DNA genotyping of the
      sample in which decomposition, pollution, mixture, degeneration, etc., have
      progressed is requested for identification. In addition, in cases of a small
      amount of sample, it is not possible to conduct checks many times. The Police
      Agency in Japan introduced the multiplex PCR system that can detect 15 kinds of
      STR genotyping and perform sex determination simultaneously using only a small
      amount of DNA.

PMID- 20815151
TI  - [Human influence on the emerging and re-emerging viral diseases].
AB  - It has been described some causes that promote the emergency or re-emergency of
      viral infections. A fundamental factor is the property of viruses to accumulate
      mutations which may help them to escape from the host immunological system,
      increasing their virulence or inducing resistance to antivirals. Nevertheless,
      there exist factors inherent to the human activity that play important roles in
      the emergency or re-emergency of viruses. These activities are related with
      traffic of exotic animals, deforestation, migration, introduction or development
      of human communities in unexplored areas and the climatic changes. Due to the
      great significance of emerging viruses as a public health concern, it is
      necessary to know different aspects of these phenomena, to take the necessary
      steps to prevent or control epidemics or pandemics.

PMID- 20815152
TI  - [Distal renal tubular dysfunction in seriously undernourished pediatric
      patients].
AB  - Seriously undernourished patients have a bigger tendency to metabolic acidosis
      than euthrophic individuals. The objective of the present work was to realize a
      study of the renal tubular function in 30 severely undernourished children. The
      investigation was a prospective, descriptive and transversal study. A test of
      overload with 5% sodium bicarbonate was realized to 30 seriously undernourished
      children whose primari etiology was marasmus, kwashiorkor or with mixed
      conditions, with ages of 6 months to 5 years, from both sexes, hemodynamically
      stable, with metabolic acidosis, hiperchloremia and positive urinary anion gap.
      The relation calcium/creatinine and the index uric acid/creatinine were
      determined. The absolute and relatives frequencies, average values and standard
      deviations were calculated. Infants represented 80% of the evaluated patients.
      The clinical forms kwashiorkor and mixed forms, of chronic evolution prevailed.
      Distal tubular renal acidosis was observed in 12 patients (40%) after the test
      overload with 5% bicarbonate. The average values of the relation
      calcium/creatinine of children <2 years was 0.362 +/- 0.414 and of children >2
      years was 0.265 +/- 0.222. The uric acid/creatinine index was 0.57 +/- 0.28.
      Metabolic acidosis is frequent in serious infantile undernourishment, which,
      according to the results observed, obeys to distal renal tubular dysfunction. The
      interpretation of the relation calcium/creatinine and the uric acid/creatinine
      index is difficult, becoming necessary to increase the investigations in these
      patients.

PMID- 20815153
TI  - [APOE-219g/T polymorphism related to serum lipid levels in atherosclerotic
      patients from Argentina].
AB  - APOE epsilon4 allele is associated with increased risk for Coronary Artery
      Disease and higher concentrations of total-cholesterol and low-density
      lipoprotein-cholesterol; however, some studies could not reproduce these results.
      This fact suggests that other genetic or environmental factors are acting on
      these associations. Quantitative variations of gene expression, conferred by
      polymorphisms in the promoter area, as -219G/T, could play also a role as a risk
      factor for CAD. Since, in a previous study, we found an association between the
      APOE epsilon4 allele and atherosclerotic lesions in males of our population, we
      investigated now whether the APOE promoter polymorphism -219 G/T is also
      associated with the presence of atherosclerotic lesions and plasma lipid levels.
      Genotypes were obtained from 380 DNA samples from patients undergoing an
      angiography study. Logistic regression analysis showed no significant
      associations between T allele, or G allele, and the presence of atherosclerotic
      lesions. Lineal regression analysis showed association between G allele and
      higher TC (p = 0.002) and LDL-c (p = 0.022) levels. After stratified by sex: TC
      (p = 0.001) and LDL-c (p = 0.020) for males, females showed no significant
      differences. For cases and controls groups, the allele G has still been
      associated with higher levels of TC (p = 0.007, p = 0.048 respectively). No
      associations for T allele were observed. We conclude that G allele of
      polymorphism -219 on the promoter of APOE gene is associated with higher TC and
      LDL-c levels in males, but this polymorphism is not acting as a risk factor of
      CAD in our population.

PMID- 20815154
TI  - Presence of human papillomavirus infection determined by hybrid capture assay in
      cervical lesions in a Venezuelan population.
AB  - The aim of this study was to establish the presence of HPV infection in cervical
      lesions in a Venezuelan population, by Hybrid Capture Assay II (HCA II), and its
      association with cytological diagnosis. The study included 1483 cervical samples
      analysed at Laboratorios CITOMED, Caracas, Venezuela, from 2005 to 2007. The
      woman age range was between 20 and 58 years, and the mean age was 28.8. HPV
      infection was determined using HCA II. The cytological diagnosis of the smears
      showed LSIL in 1120/1483 samples (75.5%), HSIL in 354/1483 (23.9%) and ASC-US, in
      9/1483 (0.6%). The positivity of HPV DNA detected by HCA II was 54.6% (811/1483).
      Of the positives cases, 138/811 (17%) presented HPV DNA of low oncogenic risk and
      673/811 (82.9%) had high-risk HPV. There were significant differences in the low
      and high oncogenic HPV type frequencies of the evaluated samples (p > 0.0001).
      Low risk HPV types were detected in 127 cases of LSIL, 9 of HSIL and 2 of ASC-US.
      High-risk HPV was detected in most of the cases: 361 LSIL, 308 HSIL and 4 ASC-US.
      Our study showed a high presence of cervical infection by human papillomavirus of
      a high risk genotype. Our results contribute to the epidemiological data that
      report diversity in the prevalence rates in different countries.

PMID- 20815155
TI  - [Nutritional evaluation, micronutrient deficiencies and anemia among female
      adolescents in an urban and a rural zone from Zulia state, Venezuela].
AB  - Female adolescents in reproductive age are a susceptible group to anemia and
      micronutrient deficiencies. The objective of this study was to know the
      nutritional, anthropometric and dietetic status, the prevalence of anemia,
      depletion of iron deposits (FeD) and Vitamin A deficiency (VAD) in female
      adolescents. Seventy-eight not pregnant female adolescents (15.9 +/- 1.1 years
      old), from an urban and a periurban zone of Maracaibo, and a rural zone near this
      city, without infectious and inflammatory processes, were analyzed. Anemia in
      adolescents was considered when Hb < 120 g/L; FeD: ferritin < 12 microg/L; VAD
      serum retinol <20 microg/dL; risk of VAD (RVAD) 20-30 microg/dL. The data were
      analyzed with the SAS program and expressed as Means +/- Standard Deviations,
      statistical significance was considered when p < 0.05. The percentage of caloric
      and protean adjustment in all groups was below the daily requirements.
      Adolescents from the rural zone showed significant lower values of weight (p =
      0.0024), height (p = 0.0027), body mass index BMI (p = 0.0487), fatty area (p =
      0.0183), MCV (p = 0.0241), MCH (p = 0.0488), MHCC (p = 0.0228), and the highest
      prevalence of anemia (66.67%), anemia+FeD (33.33%), and anemia+FeD+RVAD (5.56%),
      with respect to adolescents from the urban zone. Although, anemic adolescents
      from the rural zone showed a non significant decrease of the iron percentage
      adjustment. Iron requirements are increased during adolescence, reaching a
      maximum at the peak of growth and remaining almost as high in girls after
      menarche, to replace menstrual losses. The low iron status among adolescents from
      the rural zone determine that this is a high risk group to anemia and FeD and
      they require prevention, control and suplementation strategies.

PMID- 20815156
TI  - [Vasoconstriction is required for edema of contralateral lung after reperfusion
      injury of one lung].
AB  - Ischemia-reperfusion (IR) lung injury is a significant cause of morbidity and
      mortality in certain clinical scenarios that include transplantation,
      thromboendarterectomy and reexpansion injury of the lung. Edema of the
      contralateral lung after IR injury of one lung has been reported and this study
      was aimed to clarify the pathophysiology of this phenomenon. One-lung
      ischemia/hypoxia followed by reperfusion with either blood or an acellular plasma
      substitute was achieved in an isolated rabbit lung model by hilum clamping. After
      reperfusion, we studied the isolated effects of vasoconstriction and inflammation
      on contralateral lung injury by using papaverine or hydrocortisone as vasodilator
      and anti-inflammatory, respectively. We observed that IR of one lung induces
      edema of the contralateral lung. Absence of leukocytes and platelets in the
      perfusate or use of hydrocortisone completely inhibits IR injury. Moreover,
      papaverine suppresses edema of the contralateral, but not that of the reperfused
      lung. We concluded that IR of one lung produces edema in the contralateral lung
      that requires vasoconstriction of the latter.

PMID- 20815157
TI  - [C-reactive protein is asociated to carotid intima media thickness in patients
      with isolated hypercholesterolemia].
AB  - Studies have shown that high concentrations of total cholesterol at the expense
      of LDL cholesterol and markers of inflammation are linked with subclinical
      atherosclerosis. This study was aimed to associate the carotid intima media
      thickness (IMT) and high-sensitivity C-reactive protein (hs-CRP) in patients with
      isolated hypercholesterolemia. The investigation was descriptive, transverse and
      included 100 patients divided into a control group (normocholesterolemic) and a
      study group (hypercholesterolemic). There were no significant differences in age
      and gender distribution among the groups. The body mass index, waist
      circumference, total cholesterol and its fractions, IMT and hs-CRP were
      significantly elevated in the study group. Only in the hypercholesterolemic
      group, the IMT was significantly associated with hsCRP. In the study group, the
      mean IMT rose by quartiles of hs-CRP, reaching its highest level in the fourth
      quartile. The multiple linear regression analysis identified LDL cholesterol and
      hs-CRP as predictors of IMT only in the study group. The findings support other
      data suggesting that not only the LDL cholesterol but also hs-CRP could be an
      important factor for early atherosclerotic changes in the carotid artery of
      patients with isolated hypercholesterolemia.

PMID- 20815158
TI  - Cardiovascular drugs in human mechanical nociception: digoxin, amlodipine,
      propranolol, pindolol and atenolol.
AB  - Calcium channel blockers, beta adrenergic receptor blockers and Na/K ATPase
      inhibitors are widely used drugs, mainly for cardiovascular diseases. Their
      pharmacological targets are not restricted to the cardivascular tissue,
      nociceptive system structures also express similar targets, which strongly
      suggests a direct effect on pain sensation. To evaluate the pain intensity
      changes in outpatient groups, who receive these drugs as a therapy, a cross
      sectional sampled, randomized patient groups receiving the calcium channel
      blocker amlodipine for blood hypertension (n=45), beta adrenergic receptor
      blockers (propranolol, atenolol or pindolol; n=40) for blood hypertension, or
      digoxin (n=40) for heart failure, were compared to an aparently healthy
      volunteers control group (n=60). A calibrated noxious pressure of 890 g/mm2 was
      applied for 5 seconds on the patient's sternum. Subjective pain intensity was
      reported by the visual analog scale (VAS, 0 to 10). Pain modulation system was
      evaluated by the application of a second stimulus with a 5 minutes delay. The
      analgesic effect of the beta blockers group (propanolol, atenolol, pindolol) was
      dosage-dependant (-36.8%; P = 0.0000003), without differences among them. The
      calcium channel blocker amlodipine showed lower pain scores (-50.6%; P =
      0.0000003) than beta-receptor blockers (P = 0.0000003). Digoxin presented the
      highest pain scores (+56.5%; P = 0.0000003). All pain scores for the second
      stimulus were lower than the first stimulus and were differentially affected by
      beta-blockers (atenolol, pindolol and propanolol) and calcium channel blocker
      (amlodipine), but not by digoxin. These results suggest the influence of widely
      clinically used cardiovascular drugs on nociception.

PMID- 20815159
TI  - [Evaluation of the quality of the human spermatozoon: comparison between
      spermatic DNA integrity and semen variables].
AB  - Semen analysis does not have an absolute predictive value on fertility, however
      it is a reflection of male fertility potential, which is related to its
      spermatozoa quality and other semen variables. Great variability in human semen
      parameters has been demonstrated within a single individual, an observation that
      could explain why a male with low semen quality can successfully fertilize an
      egg. Although conventional semen analysis, such as sperm concentration, motility
      and morphology, provide important information about the clinical status of male
      fertility, new procedures to predict the sperm functional capability have been
      developed in the last decade, such as analysis of nuclear DNA integrity, which
      have improved considerably the clinical diagnosis of male infertility, and
      increased the knowledge about spermatozoa function. DNA fragmentation consist in
      interruptions, both in single and double DNA strains, that frequently occur in
      sperm samples from infertile patients. We have conducted a clinical study in
      semen samples from patients who have attended the Andrology laboratory of the
      University of Los Andes, between March 2007 and March 2009. The aim of this study
      was to compare sperm DNA integrity, analyzed by flow cytometry, with traditional
      semen parameters. Our results show remarkable correlations between conventional
      human semen variables and sperm chromatin integrity, contributing to asses an
      integral evaluation of sperm quality allowing the analysis of its fertilizing
      potential in clinical studies.

PMID- 20815160
TI  - An inexpensive antigen for serodiagnosis of Chagas' disease.
AB  - In this prospective study we evaluated the performance characteristics of a
      specific and sensitive antigen preparation (AgA) used in an enzyme-linked
      immunosorbent assay (ELISA) for the detection of anti-Trypanosoma cruzi
      antibodies in serum samples, for Chagas' disease diagnosis. The antigen
      production was achieved by combination of nutritional stress and autoclaving the
      parasites. Specificity and sensitivity were evaluated in two separate tests,
      using 152 sera from healthy individuals and 175 sera from Chagas' patients (70 by
      xenodiagnosis). Cross-reactivity was tested using 289 sera from patients who had
      a parasitological diagnosis of a disease known to induce antigenic responses
      towards T. cruzi. All of these sera were tested with our AgA-ELISA and with 3
      commercial diagnosis kits. To evaluate the agreement of results between our AgA
      ELISA and a "gold standard" test for Chagas, we tested 566 sera from an endemic
      area. RESULTS: sensitivity and specificity were 100%; cross-reactivity was the
      lowest compared with commercial kits. Overall agreement with the gold standard
      test was excellent (kappa = 0.92). AgA-ELISA exhibits levels of sensitivity,
      specificity and cross-reactivity comparable or superior to those shown, obtained
      with the commercial kits used in our country, while being at least 10 times less
      expensive. This balance between diagnostic accuracy and cost makes AgA-ELISA
      useful for blood bank screening in poor regions of the world suffering from
      Chagas' disease. Further validations of this antigenic formulation in other
      countries are necessary.

PMID- 20815161
TI  - Association of free fatty acids with the insulin-resistant state but not with
      central obesity in individuals from Venezuela.
AB  - Individuals with insulin resistance (IR) usually have upper body obesity
      phenotype, often accompanied by an increase in plasma free fatty acids (FFA).
      Since the Venezuelan population has a high frequency of IR and central obesity,
      the purpose of this work was to determine FFA levels in 47 Venezuelan
      individuals, men and women, 24-58 years old, and analyze their relationship with
      central obesity and parameters of carbohydrate and lipid metabolism. Basal
      concentrations of TG, total cholesterol, LDL-C, and HDL-C were measured, and FFA,
      glucose and insulin, at basal state and at different times after a glucose load.
      Eighteen individuals presented insulin resistance (HOMA-IR > 2.7) and 29 were non
      insulin resistant (non-IR). Insulin resistant individuals (IR) had higher waist
      circumference, BMI and basal concentrations of FFA than the non-IR. No
      differences were observed in skin folds and other basal lipids studied. The
      increased FFA seemed to be related to the IR associated to BMI and not to central
      obesity, since the difference between IR and non-IR disappeared when they were
      matched for waist circumference. After a glucose load, FFA decreased in both
      groups, but remained significantly elevated in IR subjects. This effect
      disappeared after matching for BMI or waist circumference, inferring that it was
      independent of anthropometries. FFA were positively associated with HOMA-IR,
      glucose and TG levels; however, there was.no association with BMI or waist
      circumference. These findings, and the lack of elements to support the presence
      of hepatic IR, common to increased visceral lipolysis, might suggest that the IR
      present in the obese individuals studied, might be due to an increase in
      subcutaneous fat.

PMID- 20815162
TI  - Description of envenomation by the "gusano-pollo" caterpillar (Megalopyge
      opercularis) in Venezuela.
AB  - Lepidoptera is a large order of insects, with more than 180,000 species word
      wide, showing larval stages of butterflies and moths known as wormlike
      caterpillars. Almost 12 families of butterflies around the world are capable of
      causing severe human injuries, varying from dermatitis, renal failure, hemostatic
      alterations, respiratory failure and neurotoxic symptoms. These caterpillars are
      coated in long, hair-like setae containing venom to protect themselves against
      aggressive predators. The setae cause a painful reaction, upon contact, due to
      presence of neurotoxins. These caterpillars are extensively dispersed all through
      North America and often, during the dry and wet seasons in tropical regions,
      being able to sustain two annual larval generations. There exist several species
      of Megalopyge caterpillars; however, Megalopyge opercularis is the most widely
      distributed species in Latin America and the United States. This work reports, to
      our knowledge, the first case of envenomation by the "gusano-pollo" (Megalopyge
      opercularis), a stinging caterpillar, described in Venezuela. The patient in this
      report presented severe symptoms, including systemic reactions such as intense
      hand pain irradiated to the upper arm, restricted swelling, headache, dizziness,
      serious chest distress and shock-like symptoms that required hospitalization.
      Symptoms improved upon treatment with opiaceous analgesic drugs.

PMID- 20815163
TI  - [Indications for the procedure for transvenous removing of electrodes based on
      the guidelines of U.S. societies].
AB  - The number of implanted the cardiovascular implantable electronic device(s)
      (CIED(s))--pacemakers (PM) and implantable cardioverters defibrillators (ICD)-
      increases each year. The number of CIED(s) exchange procedures as well as changes
      in models of stimulation (upgrade to dual chamber pacemakers or three chamber
      cardiac resynchronization therapy devices) also grows. Also increases the
      inactive electrode left in the cardiovascular system. The risk of infection is
      higher during the exchange of devices than with their implantation. Treatments
      for patients with multiple electrode systems are becoming a potential source of
      infection. The incidence of damage defibrillator is greater than pacemaker leads.
      Intracardiac electrodes causes the growth of connective tissue, fibrosis in the
      venous system and may cause obstruction subclavian vein or brachiocephalic
      preventing implantation needed a new electrode. Damaged and broken electrodes may
      migrate to the cavities of the heart. This increases the risk of thrombosis,
      pulmonary embolism, tricuspid valve dysfunction and serious arrhythmias. All
      these facts presented lead to the conclusion that the growing need to remove the
      electrodes (both infected and inactive) pacemaker or cardioverter defibrillator.
      There are two classes of indications to remove the electrodes. Procedures for
      removing the benefits must outweigh the risks. Should be considered for each
      patient individually and take into account the experience of the operator and its
      results. Class I indications are: lead dependent endocarditis, sepsis,
      arrhythmias or embolism secondary to the presence of lead, venous occlusion
      prevents the implantation of new electrodes, interference between the electrodes,
      an implantable device infection box. Class II includes: chronic pain in the area
      and inactive pacemaker electrodes in young people. After removal must be
      individually examined whether there is a need to implant the new layout. It
      should not be implanted in a place that has previously been infected. The
      preferred area is the opposite, iliac vein, reaching epicardial implantation.

PMID- 20815164
TI  - [Assessment of time to stimulate the function of the type of AAI in the distant
      observation in patients with sick sinus syndrome].
AB  - For the first time in 1966 vestibular stimulation has been applied. This idea is
      implemented in a patient with sinus node dysfunction and normal AV conduction.
      The aim of the study was to evaluate the time of AAI stimulation until the first
      reimplantation of stimulating system and to determine the cause of it. MATERIAL
      AND METHODS: Work is retrospective in nature. The analysis included 251 patients
      who were subjected to AAI pacemaker implantation in the period from December 1988
      to January 2009. The group consisted of 150 women and 101 men. The average age of
      patients at the time of implantation of 62.0 +/- 13.3 years (17.3 -90.2). The
      median follow-up was 7.6 +/- 4.8 years (maximum 20.1 years). For each patient,
      Wenckebach point was above 130/min. Of the 251 patients, 98 were undergoing
      treatment reimplantation of stimulating system. RESULTS: The median time to
      stimulate the function of the type of AAI was 8.69 +/- 2.4 years. The main cause
      was the exhaustion of the battery replacement--91.8% of cases, but sometimes less
      damage to the electrodes--7.1% of cases. Duration does not depend on the gender
      of the patient, or to his age at the time of implantation. CONCLUSIONS: The most
      common cause of reimplantation is battery exhausted. AAI stimulation is very
      effective treatment in the test group of patients.

PMID- 20815165
TI  - [Analysis of changes in peripheral and central nervous system in irregularly
      treated adult patients with primary congenital hypothyroidism].
AB  - Lack of thyroid hormones in the womb and the first years of life causes changes
      in the nervous system and mental retardation. The aim of the study was to assess
      changes in peripheral and central nervous system in 29 adult patients with
      primary congenital hypothyroidism (PCH) depending on the cause of the disease and
      systematic treatment of L-thyroxine. MATERIAL AND METHODS: The analysis was
      performed in 29 adult patients with PCH (16 women, 13 men) on the basis of the
      results of neurological examination, EEG, SPECT (Computer tomography single
      photon emission) of the brain. RESULTS: Changes in the nervous system were found
      in 72% of respondents. Patients who had implemented replacement therapy L
      thyroxine after completing 12 months of age showed the most neurological
      disorders. There were variations in the cranial nerves III, IX, IV and VI. In 34%
      of respondents revealed paraneoplastic cerebellar symptoms, while the pyramid,
      and extrapyramidal symptoms in 10% and 3% of the people. EEG showed changes in
      brain bioelectrical activity in the entire study group. In the 83% found a
      significant asymmetry in regional cerebral blood flow (rCBF). Hypoperfusion
      outbreak occurred mainly in the stands and leading occipital. The relationship
      between time of initiation of treatment, and the presence of a systematic change
      in the nervous system was inversely proportional. In turn, analyzing the causes
      of most PCH deviations were found in the nervous system in patients with
      athyreosis. Brain SPECT study in these patients confirmed the organic changes in
      brain development. CONCLUSIONS. The presence and extent of changes in peripheral
      and central nervous system depends on the cause PCH, pending the implementation
      of L-thyroxine treatment and systematic. Studies of brain SPECT and EEG confirmed
      the existence of developmental changes of the brain in patients with PCH.

PMID- 20815166
TI  - [Environmental conditions and family prevalence of obesity in children].
AB  - Obesity, which is a chronic systemic disease, is one the main health problems in
      contemporary society. Prevalence of obesity in childhood obesity and promotes the
      occurrence of many chronic diseases into adulthood. The aim of the study was to
      assess the relationship between obesity and child obesity, and lifestyle
      conditions in the family. MATERIAL AND METHODS: The study group included 100
      children aged 4-18 years, with a body mass index (BMI) above 97 centile.
      Respondents (44 girls and 56 boys) were selected from among children treated in
      the period from April 2008 to May 2009, the Department of Pediatric Surgery and
      Urology with general diseases, scheduled treatments not associated with obesity.
      In each patient, based on a prepared questionnaire, has been interviewed for
      dietary habits, family history in the direction of obesity and other
      comorbidities. The measurements of height and weight and abdominal circumference
      and waist were also made. RESULTS: The studies show that obesity is most common
      in children aged 9-13 years. The majority of obese children has errors habits. In
      the study group found the relationship between the prevalence of obesity in
      children and obesity occurring in the immediate family. It was observed that, in
      the oldest patients (14-18 years) most attempts to treat obesity. CONCLUSIONS:
      The percentage of obesity in children and their parents were similar and remained
      tied with overweight and obesity in the family. Therapeutic interventions are
      undertaken mainly in older children. In addition, children aged 9-13 years
      usually reach for foods with a fast food, which can negatively associated with
      rarely undertaken interventions aimed at weight loss.

PMID- 20815167
TI  - [Differences in cognitive functioning of men and women with a diagnosis of
      depression].
AB  - Every year about 100 million people around the world, manifested symptoms of
      depression. The prevalence of depressive disorders concern for at least 15% of
      adult women and 10% of men. The aim of the study was to evaluate the
      effectiveness of selected cognitive processes in a group of men and women with
      recurrent depressive disorders. MATERIAL AND METHODS: The survey involved 30
      people (age: 23-62 years, mean age = 50.46 years, SD = 8.97): 16 women (53.33%;
      age: 23-59 years, mean age = 51.16 years, SD = 4.74) and 14 men (46.67%,
      respectively, age: 23-62 years, mean age = 51.41 years, SD = 12.07) hospitalized
      in Department of Adult Psychiatry, Medical University of Lodz. The study used
      psychological tests designed to assess the effectiveness of cognitive processes
      (learning curve Luria, a test plot away, Stroop test, verbal test fluencji by
      Lucki) and Hamilton depression rating scale (HDRS, consists of 21-items).
      RESULTS: Observed no statistically significant differences between treatment
      groups in the trials conducted. Women in the study group obtained better results
      compared to men in the learning curve Luria, Stroop test and verbal fluency test
      by Lucki. Men came out better in the test plot of the road. There were no
      differences between treatment groups in severity of depression measured HDRS.
      CONCLUSIONS: The results showed no statistically significant differences between
      men and women in the trials conducted evaluating the effectiveness of cognitive
      functioning. Women in the study group obtained better results compared to men in
      the trials evaluating the effectiveness of short-and long-term verbal memory,
      verbal memory and verbal fluidity. Men in the test group proved better than women
      in tests assessing visual-motor coordination and visual-spatial memory
      operational.

PMID- 20815168
TI  - [Knowledge of patients from the rural environment on the risk factors and
      prevention of cardiovascular diseases].
AB  - Cardiovascular diseases (CVDs) are the leading cause of death in Poland. The aim
      of the study was to assess the knowledge of patients from the rural environment
      on the risk factors and prevention CVDs. MATERIAL AND METHODS: In the period from
      January to February 2006. one hundred and twenty patients [69 (57.5%) females and
      51 (42.5%) males] from Primary Care Practice in Zabludow living in rural areas in
      the vicinity of Bialystok were interviewed using questionnaires developed by the
      authors of the work. It contained questions on demographic data (gender, age,
      education and residence), health status and level of knowledge about risk factors
      and prevention CVDs. RESULTS: The vast majority of patients had a thorough
      understanding of risk factors CVDs. The least known factor is diabetes--just as
      the second test (55.8%) believe that it contributes to the formation of CVDs. As
      prophylaxis 77.5% of respondents reported a diet low in salt, and 75%--regular
      physical activity. Advancing our knowledge about the disease as an existing
      preventive recognized 70.8% of respondents. Comparing knowledge of patients with
      the knowledge of healthy CVDs participating in the survey stated that they know
      more about risk factors and prevention CVDs than the differences are
      statistically significant (p < 0.05). Better educated person knows more about
      risk factors and prevention of CVDs than the less educated people. These
      differences were statistically significant (p < 0.05). CONCLUSIONS: Examined
      patients living in rural areas have a wide knowledge on risk factors and
      prevention CVDs. This applies especially to people with higher education or with
      known cardiovascular diseases. People with lower education require more attention
      and education. Emphasis should be given to promoting information on the impact of
      diabetes on the development of CVDs.

PMID- 20815169
TI  - [How can we establish hospital ethics committees?].
AB  - The necessity of establishing hospital ethics committees (HEC) in Poland is
      obvious. Limitations of such initiatives are related with lack of standards,
      financial support, legal provisions and well trained and educated candidates on
      members of HECs. HECs should: protect patient's rights and their beneficience,
      facilitate ethics education for doctors and other health professionals and
      provide ethics advice in individual cases. Members of HECs should present a broad
      range of disciplines and backgrounds. They should provide a comprehensive and
      reliable opinion in which all medical, legal and ethical aspects should be
      mentioned. All members should have a basic knowledge of medical ethics, related
      legal provisions and Medical Code of Ethics. Different models of ethics support
      should be provided. Ethical consultation of single specialist and committee or
      subcommittee debates are possible choices. It is necessary to prepare operating
      procedures for HECs which will provide standard and unified formalities for all
      referred cases. Hospital management who is interested in establishing HEC should
      provide adequate financial support. Members of HECs should be encouraged to
      upgrade their skills and knowledge.

PMID- 20815170
TI  - [TA90--new neoplastic marker].
AB  - TA90 is a glycoprotein, occurring on the cell surface of many types of cancer.
      Determination of its concentration in human serum appears to be a good screening
      test in the direction of many cancers, and also can act as a monitoring index of
      disease, particularly in respect of melanoma. Further clinical studies are
      necessary in order to obtain accurate data on the TA90, and after that its
      determination might be made to everyday clinical practice in oncology.

PMID- 20815171
TI  - [Application scintigraphy in evaluation of salivary gland function].
AB  - The salivary glands belong to the exocrine glands. There are tree main pairs of
      salivary glands: parotid, submandibular, sublingual. Several modalities are used
      for salivary gland imaging, such as sonography, computer tomography and magnetic
      resonance imaging. The aim of these methods is mainly to present morphological
      impairment. Parenchymal function and excretion function of all salivary glands
      can be quantified by scintigraphy. After single intravenous injection of 99mTc
      pertechnetate sequential images are acquired up to 25-40 minutes. Usually about
      fifteen minutes postinjection 3 ml of lemon juice are administered intraorally as
      sialogogue. Salivary scintigraphy can estimate the severity of salivary gland
      involvement and function disorders, which may not be accurately reflected by the
      morphological damage. The clinical impact of scintigraphy has been reported in
      multiple salivary glands diseases, such as Sjogren's syndrome, sialolithiasis
      with or without parenchymal damage, iatrogenic irradiation of the salivary glands
      for therapy of head and neck tumors or radioiodine treatment of thyroid cancer.
      No other method can give so much information about function of salivary glands.
      Scintigraphy is noninvasive examination, easy to perform, reproducible and well
      tolerated by the patient.

PMID- 20815172
TI  - [Usefulness of endothelin-1 determinations in the diagnosis of cardiovascular
      diseases].
AB  - Factor involved in the pathogenesis of cardiovascular diseases, especially
      coronary heart disease is the endothelium. The balance between endothelial
      substances originating from the action, and narrowed the extension is the essence
      of vascular hemostasis. The main dish is shrinking substances endothelin-1 (ET
      1). The aim of the study was to determine the role of signs ET-1 levels in the
      diagnosis of cardiovascular diseases, especially coronary heart disease. In
      numerous reports described the impact of increased blood pressure, caused by the
      press on blood vessels. Most authors reported higher concentrations of ET-1 in
      serum of patients with ischemic heart disease, particularly its unstable
      character. High values were observed in patients with myocardial infarction. ET-1
      level in the blood is markedly increased in patients with heart failure,
      correlating with NYHA functional class. High concentrations of ET-1 in many
      disease entities, and thus its low specificity makes the need for further
      research on the importance of this substance in the diagnosis of cardiovascular
      diseases.

PMID- 20815173
TI  - [Etiology of colorectal cancer and antioxidant barrier of the organism].
AB  - Colorectal cancer is a serious medical and economic problem in Poland, as the
      detection and results of its treatment are very low. Due to this fact, medical
      research is still conducted in order to find out the symptoms of this tumor and
      proper preventive measures. According to one hypothesis of carcinogenesis, the
      process of creating the tumor begins and develops when the balance between the
      production of reactive oxygen species (ROS) and their deactivation by the
      "antioxidant protective barrier of the organism" is disturbed. As a result of
      this theory, it has been decided to examine the plasma concentration of the
      dietary minerals which work as antioxidants. The results entailed conclusions
      which prove the free radicals theory of carcinogenesis. They also confirm the
      part which the antioxidant protective barrier plays in the defence against ROS
      and their carcinogenic consequences.

PMID- 20815174
TI  - [Advanced oxidation protein products. Part II. The significance of oxidation
      protein products in the pathomechanism of diabetes and its complications].
AB  - Advanced oxidation protein products (AOPP) are derivatives of oxidation-modified
      albumin which are formed in conditions of intensified oxidative stress. In
      diabetes the formation of AOPP is induced by intensified glycooxidation
      processes, oxidant-antioxidant imbalance, and coexisting inflammation. On the
      other hand, AOPP intensify the metabolic disturbances in diabetes and the
      progression of its vascular complications. Concentrations of AOPP is
      significantly higher in diabetes, especially type 2 (about twice) in comparison
      to healthy people. Changes in AOPP level are connected with poor glycemic
      control, the chronic state of the disease, dyslipidemia, and diabetic
      complications, particularly nephropathy. AOPP level is useful marker for
      monitoring development of diabetic disorders and can be helpful in monitoring of
      applied therapy.

PMID- 20815175
TI  - [Sirtuins--modulation of their activity as a novel therapeutic target].
AB  - Sirtuins are a NAD(+)-dependent deacetylases involved in several cellular
      processes like e.g. transcriptional silencing, regulation of apoptosis, fat
      homeostasis and aging. Mammalian sirtuins are located in cytoplasm, nucleus as
      well as mitochondria. The sirtuins exhibit a number of intriguing biological
      properties and increase of their activity was correlated with several important
      physiological functions including regulation of glucose level, impact on
      angiogenesis and neuroprotection. On the other hand, results of research carried
      out on the sirtuins activity suggest that their overexpression could be related
      to Parkinson's disease, or some kind of cancer, however it was also shown that
      sirtuin inhibitors could be useful for the treatment of cancers by inhibition the
      formation of tumours and induction of apoptosis. Life span-prolonging effects
      have also been observed in yeast cells, nematodes and flies upon the
      overexpression of Sirtuin-1. Although sirtuins appeared as a Janus-faced enzymes
      selective modulators of their activity could be helpful in treatment of several
      age-related diseases.

PMID- 20815176
TI  - [The importance of vitamin B12 in psychiatry].
AB  - The article drew attention to the construction of a vitamin B12 deficiency and
      its importance in the human body. Emphasizes the role of cobalamin as a
      structural element involved, among others cobamides in such reactions as the
      synthesis of purine and pyrimidine biosynthesis or choline. Two metabolically
      active forms of cobalamin: methylcobalamin and adenosylcobalamin and their
      importance to the human body were presented. The process of absorption of vitamin
      B12 and methionine in revealing the importance of the neurological symptoms was
      described. The chemical importance and cause vitamin B12 deficiency was stressed.
      The attention was paid upon the role of acid in methylomalon determination of
      vitamin B12 deficiency in the human body. Disclosure reports analyzed the
      relationship of vitamin B12 from the emergence of psychotic symptoms. Particular
      attention is given to teams which binds to the vitamin B12 deficiency-
      depressive, delusional and manic. Based on case reports were analyzed cases with
      deficiency symptoms associated with a deficit of vitamin B12. Also points to the
      possibility of diagnosing cobalamin deficiency even before the onset of clinical
      symptoms.

PMID- 20815177
TI  - [Anxiety and depression in ulcerative colitis and Lesniovsky-Crohn's disease].
AB  - Ulcerative colitis and Lesniovsky-Crohn's disease are classified as idiopathic
      diseases. The study highlighted the role of the immune system, environmental and
      behavioral factors. Lists of infectious agents relevant to the development of
      ulcerative colitis and morbus Crohni, indicating the importance of the
      NOD2/CARD15 mutations. Quoted the results of studies on the effect of stress and
      immune response in patients with diagnosed ulcerative colitis. Discusses the
      implications arising from somatic mental patients, having regard to the causes of
      social isolation of patients and their rejection of social support. The study
      examined the results of research on quality of life of patients treated for
      ulcerative colitis and Crohn's disease. Stressed the importance of depression and
      anxiety in the development of idiopathic inflammatory bowel diseases. The results
      of studies showing the treatment of depression and anxiety as predictors of
      development idiopathic intestinal diseases were cited. The possibility of
      increased incidence of schizophrenia was excluded among people living with
      inflammatory nonspecific bowel disease.

PMID- 20815178
TI  - [Professional burnout among psychiatrists].
AB  - Article focuses on the problem of burnout, which affects the medical community.
      Approximates the three most common definitions of burnout, particularly analyzing
      the components of a three-dimensional theory of C. Maslach burnout (emotional
      exhaustion, depersonalization, reduced sense of personal achievement). The author
      lists the characteristics of socially useful occupations, which may facilitate
      the emergence of team burnout, among others, lack of professional success, the
      requirement to engage in group work. The article drew attention to certain
      personality traits that may predispose to disclose the team burnout--to cope with
      stress in a passive manner, avoiding, with the personality traits neurotic,
      assessment of the situation in terms of risk. Brought closer the results of
      several studies, including environmental health, noting the psychiatrists. Sought
      to draw attention to the factors that protect against the occurrence of team
      burnout. It was observed that job satisfaction served as a protective role. They
      also highlighted the consequences of team burnout among medical staff--frequent
      changes of jobs, the increasing violence against patients, withdrawal from
      medical practice, for reasons of sickness absenteeism, conflicts in family life.

PMID- 20815179
TI  - [Metabolic syndrome in dialyzed patients. Advanced glycation end-products,
      adipocytokines, and principles of treatment].
AB  - Metabolic syndrome (MeS) in dialyzed patients, especially in peritoneal dialysis,
      runs with increased serum concentration of adipocytokines and intensified the
      process of advanced glycation end-product formation and its consequences.
      Treatment of MeS in dialyzed patients is as difficult as in general population.
      Attention was paid for therapeutic aspects, associated with treatment of end
      stage renal disease and with dialysis procedure, which may influence the course
      of MeS.

PMID- 20815180
TI  - Assessing fatigue in multiple sclerosis: shedding light on the elephant in the
      dark.

PMID- 20815181
TI  - Expanding the clinical spectrum of OSA--an association with pulmonary embolism?

PMID- 20815182
TI  - Neurobehavioral dynamics following chronic sleep restriction: dose-response
      effects of one night for recovery.
AB  - OBJECTIVE: Establish the dose-response relationship between increasing sleep
      durations in a single night and recovery of neurobehavioral functions following
      chronic sleep restriction. DESIGN: Intent-to-treat design in which subjects were
      randomized to 1 of 6 recovery sleep doses (0, 2, 4, 6, 8, or 10 h TIB) for 1
      night following 5 nights of sleep restriction to 4 h TIB. SETTING: Twelve
      consecutive days in a controlled laboratory environment. PARTICIPANTS: N = 159
      healthy adults (aged 22-45 y), median = 29 y). INTERVENTIONS: Following a week of
      home monitoring with actigraphy and 2 baseline nights of 10 h TIB, subjects were
      randomized to either sleep restriction to 4 h TIB per night for 5 nights followed
      by randomization to 1 of 6 nocturnal acute recovery sleep conditions (N = 142),
      or to a control condition involving 10 h TIB on all nights (N = 17). MEASUREMENTS
      AND RESULTS: Primary neurobehavioral outcomes included lapses on the Psychomotor
      Vigilance Test (PVT), subjective sleepiness from the Karolinska Sleepiness Scale
      (KSS), and physiological sleepiness from a modified Maintenance of Wakefulness
      Test (MWT). Secondary outcomes included psychomotor and cognitive speed as
      measured by PVT fastest RTs and number correct on the Digit Symbol Substitution
      Task (DSST), respectively, and subjective fatigue from the Profile of Mood States
      (POMS). The dynamics of neurobehavioral outcomes following acute recovery sleep
      were statistically modeled across the 0 h-10 h recovery sleep doses. While TST,
      stage 2, REM sleep and NREM slow wave energy (SWE) increased linearly across
      recovery sleep doses, best-fitting neurobehavioral recovery functions were
      exponential across recovery sleep doses for PVT and KSS outcomes, and linear for
      the MWT. Analyses based on return to baseline and on estimated intersection with
      control condition means revealed recovery was incomplete at the 10 h TIB (8.96 h
      TST) for PVT performance, KSS sleepiness, and POMS fatigue. Both TST and SWE were
      elevated above baseline at the maximum recovery dose of 10 h TIB. CONCLUSIONS:
      Neurobehavioral deficits induced by 5 nights of sleep restricted to 4 h improved
      monotonically as acute recovery sleep dose increased, but some deficits remained
      after 10 h TIB for recovery. Complete recovery from such sleep restriction may
      require a longer sleep period during 1 night, and/or multiple nights of recovery
      sleep. It appears that acute recovery from chronic sleep restriction occurs as a
      result of elevated sleep pressure evident in both increased SWE and TST.

PMID- 20815183
TI  - Effects of modafinil on the sleep EEG depend on Val158Met genotype of COMT.
AB  - STUDY OBJECTIVES: Modafinil may promote wakefulness by increasing cerebral
      dopaminergic neurotransmission, which importantly depends on activity of catechol
      O-methyltransferase (COMT) in prefrontal cortex. The effects of modafinil on
      sleep homeostasis in humans are unknown. Employing a novel sleep-pharmacogenetic
      approach, we investigated the interaction of modafinil with sleep deprivation to
      study dopaminergic mechanisms of sleep homeostasis. DESIGN: Placebo-controlled,
      double-blind, randomized crossover study. SETTING: Sleep laboratory in temporal
      isolation unit. PARTICIPANTS: 22 healthy young men (23.4 +/- 0.5 years)
      prospectively enrolled based on genotype of the functional Val158Met polymorphism
      of COMT(10 Val/Val and 12 Met/Met homozygotes). INTERVENTIONS: 2 x 100 mg
      modafinil and placebo administered at 11 and 23 hours during 40 hours prolonged
      wakefulness. MEASUREMENTS AND RESULTS: Subjective sleepiness and EEG markers of
      sleep homeostasis in wakefulness and sleep were equally affected by sleep
      deprivation in Val/Val and Met/Met allele carriers (placebo condition). Modafinil
      attenuated the evolution of sleepiness and EEG 5-8 Hz activity during sleep
      deprivation in both genotypes. In contrast to caffeine, modafinil did not reduce
      EEG slow wave activity (0.75-4.5 Hz) in recovery sleep, yet specifically
      increased 3.0-6.75 Hz and > 16.75 Hz activity in NREM sleep in the Val/Val
      genotype of COMT. CONCLUSIONS: The Val158Met polymorphism of COMT modulates the
      effects of modafinil on the NREM sleep EEG in recovery sleep after prolonged
      wakefulness. The sleep EEG changes induced by modafinil markedly differ from
      those of caffeine, showing that pharmacological interference with dopaminergic
      and adenosinergic neurotransmission during sleep deprivation differently affects
      sleep homeostasis.

PMID- 20815184
TI  - Sleep duration and cardiovascular disease: results from the National Health
      Interview Survey.
AB  - BACKGROUND: Previous studies have shown that both short and long sleep durations
      are related to increased likelihood of diabetes and hypertension. However, the
      relation between sleep duration and cardiovascular disease (CVD) is not clear. We
      examined the hypothesis that compared with sleep duration of 7 hours, shorter and
      longer sleep durations are independently related to CVD. METHODS: We conducted a
      cross-sectional study of 30,397 National Health Interview Survey 2005
      participants > or = 18 years of age (57.1% women). Sleep duration was categorized
      as < or = 5 hours, 6 hours, 7 hours, 8 hours, and > or = 9 hours. The main
      outcome of interest was the presence of any CVD (n = 2146), including myocardial
      infarction, angina, and stroke. RESULTS: We found both short and long sleep
      durations to be independently associated with CVD, independent of age, sex, race
      ethnicity, smoking, alcohol intake, body mass index, physical activity, diabetes
      mellitus, hypertension, and depression. Compared with a sleep duration of 7 h
      (referent), the multivariate odds ratio (95% confidence interval) of CVD was 2.20
      (1.78, 2.71), 1.33 (1.13, 1.57), 1.23 (1.06, 1.41), and 1.57 (1.31, 1.89) for
      sleep duration < or = 5 h, 6 h, 8 h, and > or = 9 h. This association persisted
      in subgroup analyses by gender, race-ethnicity, and body mass index categories.
      Also, similar associations were observed when we examined myocardial infarction
      and stroke separately. CONCLUSION: Compared with sleep duration of 7 h, there was
      a positive association between both shorter and longer sleep durations and CVD in
      a representative sample of US adults. These results suggest that sleep duration
      may be an important marker of CVD.

PMID- 20815185
TI  - Effects of reducing or eliminating resident work shifts over 16 hours: a
      systematic review.
AB  - STUDY OBJECTIVES: The Institute of Medicine (IOM) has called for the elimination
      of resident work shifts exceeding 16 hours without sleep. We sought to
      comprehensively evaluate the effects of eliminating or reducing shifts over 16
      hours. DESIGN AND OUTCOME MEASURES: We performed a systematic review of published
      and unpublished studies (1950-2008) to synthesize data on all intervention
      studies that have reduced or eliminated U.S. residents' extended shifts. A total
      of 2,984 citations were identified initially, which were independently reviewed
      by two authors to determine their eligibility for inclusion. All outcomes
      relevant to quality of life, education, and safety were collected. Study quality
      was rated using the U.S. Preventive Services Task Force methodology. MEASUREMENTS
      AND RESULTS: Twenty-three studies met inclusion criteria (kappa = 0.88 [95% CI,
      0.77-0.94] for inclusion decisions). Following reduction or elimination of
      extended shifts, 8 of 8 studies measuring resident quality of life found
      improvements. Four of 14 studies that assessed educational outcomes found
      improvements, 9 found no significant changes, and one found education worsened.
      Seven of 11 identified statistically significant improvements in patient safety
      or quality of care; no studies found that safety or care quality worsened.
      CONCLUSIONS: In a systematic review, we found that reduction or elimination of
      resident work shifts exceeding 16 hours did not adversely affect resident
      education, and was associated with improvements in patient safety and resident
      quality of life in most studies. Further multi-center studies are needed to
      substantiate these findings, and definitively measure the effects of eliminating
      extended shifts on patient outcomes.

PMID- 20815186
TI  - Sleeping like a baby--does gender influence infant arousability?
AB  - INTRODUCTION: Victims of the sudden infant death syndrome (SIDS) may have
      preexisting abnormalities in their arousal pathways, inhibiting the progression
      of subcortical activation (SCA) to full cortical arousal (CA). Approximately 60%
      of SIDS victims are male, and it has been suggested that male infants have
      delayed cortical maturation compared to females. We hypothesized that CA
      frequency would be lower and CA threshold would be higher in male infants during
      both active (AS) and quiet (QS) sleep. METHODS: 50 healthy term infants (21 male,
      29 female) were studied with daytime polysomnography at 2-4 weeks and 2-3 months
      after birth. Arousal from sleep was induced using a pulsatile air-jet to the
      nostrils at increasing pressures. RESULTS: At 2-4 weeks, arousability from AS was
      similar in males and females, however during QS, male infants required a lower
      stimulus to induce SCA and CA. This gender difference in arousal threshold was
      not observed at 2-3 months. CA frequencies were similar between genders during
      both sleep states at both ages, though overall, CA was more frequent in AS than
      in QS. CONCLUSIONS: This study demonstrated that at 2-4 weeks, male infants were
      easier to arouse than female infants during QS. There were no significant effects
      of gender on total arousability or SCA and CA frequencies at 2-3 months, the age
      of peak SIDS incidence. Thus, although male infants are at greater risk of SIDS
      than female infants, this difference is unlikely to be associated with gender
      differences in CA threshold or frequency.

PMID- 20815187
TI  - Fatigue in multiple sclerosis: mechanisms, evaluation, and treatment.
AB  - Among patients with multiple sclerosis (MS), fatigue is the most commonly
      reported symptom, and one of the most debilitating. Despite its high prevalence
      and significant impact, fatigue is still poorly understood and often under
      emphasized because of its complexity and subjective nature. In recent years, an
      abundance of literature from specialists in sleep medicine, neurology,
      psychiatry, psychology, physical medicine and rehabilitation, and radiology have
      shed light on the potential causes, impact, and treatment of MS-related fatigue.
      Though such a diversity of contributions clearly has advantages, few recent
      articles have attempted to synthesize this literature, and existing overviews
      have focused primarily on potential causes of fatigue rather than clinical
      evaluation or treatment. The aims of this review are to examine, in particular
      for sleep specialists, the most commonly proposed primary and secondary
      mechanisms of fatigue in MS, tools for assessment of fatigue in this setting, and
      available treatment approaches to a most common and challenging problem.

PMID- 20815188
TI  - Snoring and the risk of obstructive sleep apnea in patients with pulmonary
      embolism.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is associated with prothrombotic
      effects that could lead to venous thromboembolic disease. We performed a
      prospective cross-sectional study to determine the prevalence of snoring and risk
      of OSA in patients with acute pulmonary embolism (PE). METHODS: We evaluated 270
      consecutive patients who underwent a computed tomographic angiogram for suspected
      PE. Patients without PE served as a control group. Demographic and clinical
      characteristics were analyzed. The Berlin Questionnaire was used to determine the
      presence of snoring and the risk of OSA. A subset of patients also underwent
      formal nocturnal polysomnography. RESULTS: PE was present in 71 (26%) of the 270
      patients who underwent a computed tomographic angiogram. When compared with
      patients without PE, patients with PE had a significantly higher prevalence of
      snoring (75% vs 50%, odds ratio = 2.91, 95% confidence interval: 1.60, 5.33, P =
      0.001) and an increased risk of having OSA, as defined by the Berlin
      Questionnaire (65% vs 36%, odds ratio = 3.25, confidence interval: 1.84, 5.72, P
      < 0.001). Results from the multivariate analysis showed that PE was independently
      associated with risk of OSA (OR = 2.78, P = 0.001). CONCLUSIONS: We found a
      higher prevalence of snoring and high risk of OSA in patients diagnosed with
      acute PE, in comparison with patients in whom PE was suspected but ruled out.
      This association might be independent of other risks factors common to both OSA
      and PE. Therefore, OSA may represent a risk factor for the development of PE.

PMID- 20815189
TI  - Differences in craniofacial structures and obesity in Caucasian and Chinese
      patients with obstructive sleep apnea.
AB  - STUDY OBJECTIVES: To explore differences in craniofacial structures and obesity
      between Caucasian and Chinese patients with obstructive sleep apnea (OSA).
      DESIGN: Inter-ethnic comparison study. SETTING: Two sleep disorder clinics in
      Australia and Hong Kong. PATIENTS: 150 patients with OSA (74 Caucasian, 76
      Chinese). INTERVENTIONS: Anthropometry, cephalometry, and polysomnography were
      performed and compared. Subgroup analyses after matching for: (1) body mass index
      (BMI); (2) OSA severity. MEASUREMENTS AND RESULTS: The mean age and BMI were
      similar between the ethnic groups. Chinese patients had more severe OSA (AHI 35.3
      vs 25.2 events/h, P = 0.005). They also had more craniofacial bony restriction,
      including a shorter cranial base (63.6 +/- 3.3 vs 77.5 +/- 6.7 mm, P < 0.001),
      maxilla (50.7 +/- 3.7 vs 58.8 +/- 4.3 mm, P < 0.001) and mandible length (65.4 +/
      4.2 vs 77.9 +/- 9.4 mm, P < 0.001). These findings remained after correction for
      differences in body height. Similar results were shown in the BMI-matched
      analysis (n = 66). When matched for OSA severity (n = 52), Chinese patients had
      more craniofacial bony restriction, but Caucasian patients were more overweight
      (BMI 30.7 vs 28.4 kg/m2, P = 0.03) and had a larger neck circumference (40.8 vs
      39.1 cm, P = 0.004); however, the ratios of BMI to the mandible or maxilla size
      were similar. CONCLUSIONS: Craniofacial factors and obesity contribute
      differentially to OSA in Caucasian and Chinese patients. For the same degree of
      OSA severity, Caucasians were more overweight, whereas Chinese exhibited more
      craniofacial bony restriction.

PMID- 20815190
TI  - The effects of sleep-disordered breathing on arterial stiffness are modulated by
      age.
AB  - STUDY OBJECTIVES: To identify associations between sleep-disordered breathing
      (SDB) and arterial stiffness. SETTING: Nested cross-sectional study.
      PARTICIPANTS: One hundred fifty-three participants (ages 45-77 years, 43% women)
      in the population-based Wisconsin Sleep Cohort. Eighty-three had SDB and were not
      using continuous positive airway pressure therapy. INTERVENTIONS: Measurement of
      aortic pulse wave velocity (PWV) by arterial tonometry. Nocturnal
      polysomnography. MEASUREMENTS AND RESULTS: SDB was defined as an apnea-hypopnea
      index (AHI) > or = 5 events/hour of sleep. By study design those with SDB had
      higher mean (SD) AHI (17.6 [16.2] vs 2.2 [1.3] events/h), as well as lower
      average nocturnal O2 saturation (91.5 [2.1] vs 93.0 [1.4] %, P < 0.001) and
      larger waist circumference (102.5 [13.2] vs 92.5 [12.5] cm, P < 0.001), but they
      had similar central aortic systolic (122.8 [15.1] vs 119.1 [11.8] mm Hg, P =
      0.100) and diastolic blood pressures (77.1 [9.4] vs 77.4 [8.6] mm Hg, P = 0.834),
      and PWV (9.06 [2.15] vs 8.51 [1.88] m/s; all P > 0.10). Markers of SDB that were
      correlated with PWV were nocturnal O2 saturation (r = -0.24, P = 0.004) and AHI
      (r = 0.18, P = 0.032); however, these associations were not statistically
      significant after adjustment. In subjects not on antihypertensive medications, a
      significant interaction between nocturnal O2 saturation and age was identified
      (beta = -0.019, P = 0.039), such that the effect of nocturnal oxygen O2 on PWV
      increased with age (adjusted R2 = 0.468). CONCLUSIONS: Adverse effects of
      nocturnal oxygen desaturation on PWV are seen among normotensive individuals and
      are amplified with aging. Integrated assessment of SDB is necessary to
      characterize its effects on arterial stiffness.

PMID- 20815191
TI  - The impact of partial sleep deprivation on moral reasoning in military officers.
AB  - STUDY OBJECTIVES: The present study explores the impact of long-term partial
      sleep deprivation on the activation of moral justice schemas, which are suggested
      to play a prominent role in moral reasoning and the formation of moral judgments
      and behavior. DESIGN: Participants judged 5 dilemmas in rested and partially
      sleep deprived condition, in a counterbalanced design. SETTING: In classroom and
      field exercises at the Norwegian Naval Academy and the Norwegian Army Academy.
      PARTICIPANTS: Seventy-one Norwegian naval and army officer cadets. MEASUREMENTS
      AND RESULTS: The results showed that the officers' ability to conduct mature and
      principally oriented moral reasoning was severely impaired during partial sleep
      deprivation compared to the rested state. At the same time, the officers became
      substantially more rules-oriented in the sleep deprived condition, while self
      oriented moral reasoning did not change. Interaction effects showed that those
      officers who displayed high levels of mature moral reasoning (n = 24) in the
      rested condition, lost much of this capacity during sleep deprivation in favor of
      a strong increase in rules-oriented moral reasoning as well as self-orientation.
      Conversely, officers at low levels of mature moral reasoning in rested condition
      (n = 23) were unaffected by sleep deprivation. CONCLUSIONS: The present data show
      that long-term partial sleep deprivation has an impact on the activation of moral
      justice schemas, and consequently on the ability to make moral justice judgments.

PMID- 20815192
TI  - A descriptive analysis of neck myoclonus during routine polysomnography.
AB  - STUDY OBJECTIVES: Although episodes of neck myoclonus (head jerks) in REM sleep
      have a characteristic appearance, they have so far not been described
      systematically in video-polysomnography. This study assesses the occurrence,
      frequency, and characteristics of neck myoclonus in REM sleep in a prospective
      sleep disorder cohort, and investigates clinical correlates and associations with
      medication. SETTING: University hospital sleep disorders center. PARTICIPANTS:
      Two-hundred twenty-eight mixed sleep disorder patients. INTERVENTIONS: Not
      applicable. MEASUREMENTS AND RESULTS: REM sleep was screened visually for short
      "stripe-shaped" movement-induced artifacts visible vertically over the EEG leads
      in polysomnographic registration. If such artifact was present, the synchronized
      video was inspected for the presence of neck myoclonus. Out of 205 patients,
      54.6% (n = 112) had neck myoclonus during REM sleep. The mean neck myoclonus
      index was 1.0 +/- 2.7/h REM sleep. Younger patients had a higher neck myoclonus
      index than older patients (< 45 years versus 45-60 years versus > 60 years: 1.8
      +/- 4.2 versus 0.6 +/- 1.1 versus 0.5 +/- 1.1; P = 0.004). Ninety-five percent of
      subjects < 45 years had a neck myoclonus index between 0 and 9.4/h; 95% of
      subjects > 45 years had a neck myoclonus index between 0 and 2.7/h. Patients on
      benzodiazepine treatment had no neck myoclonus (0/112 vs. 13/93; P < 0.001). In
      23 patients, additional surface neck EMG was performed. EMG activation associated
      with neck myoclonus had a mean duration of 0.6 +/- 0.4 sec. Correlation between
      duration of neck EMG activation and movement-induced EEG artifact duration was
      very high (rho = 0.96; P < 0.001). CONCLUSIONS: Neck myoclonus is common during
      REM sleep and more frequent in younger individuals. This could indicate that neck
      myoclonus during REM sleep is a physiological phenomenon. If there is a cut-off
      distinguishing normal from excessive has to be investigated in further studies.

PMID- 20815193
TI  - The utility of single-channel nasal airflow pressure transducer in the diagnosis
      of OSA at home.
AB  - RATIONALE: Given the high prevalence of obstructive sleep apnea (OSA) and the
      demand on polysomnography (PSG), there is a need for low cost accurate simple
      diagnostic modalities that can be easily deployed in primary care to improve
      access to diagnosis. STUDY OBJECTIVES: The aim was to examine the utility of
      single-channel nasal airflow monitoring using a pressure transducer at home in
      patients with suspected OSA. DESIGN: Cross-sectional study SETTING: Laboratory
      and home PARTICIPANTS: The study was conducted in two populations. Consecutive
      patients with suspected OSA were recruited from the sleep disorders clinic at a
      tertiary referral center and from 6 local metropolitan primary care centers.
      INTERVENTIONS: All patients answered questionnaires and had laboratory PSG. Nasal
      airflow was monitored for 3 consecutive nights at home in random order either
      before or after PSG. RESULTS: Atotal of 193 patients participated (105 sleep
      clinic patients and 88 from primary care). The mean bias PSG apnea hypopnea index
      (AHI) minus nasal flow respiratory disturbance index (NF RDI) was -4.9 events per
      hour with limits of agreement (2 SD) of 27.8. NF RDI monitored over 3 nights had
      high accuracy for diagnosing both severe OSA (defined as PSG AHI > 30 events per
      hour) with area under the receiver operating characteristic curve (AUC) 0.92 (95%
      confidence interval (CI) 0.88-0.96) and any OSA (PSG AHI > 5), AUC 0.87 (95% CI
      0.80-0.94). CONCLUSIONS: Single-channel nasal airflow can be implemented as an
      accurate diagnostic tool for OSA at home in both primary care and sleep clinic
      populations.

PMID- 20815194
TI  - Comparison between a single-channel nasal airflow device and oximetry for the
      diagnosis of obstructive sleep apnea.
AB  - RATIONALE: The most common single channel devices used for obstructive sleep
      apnea (OSA) screening are nasal airflow and oximetry. No studies have directly
      compared their role in diagnosing OSA at home. STUDY OBJECTIVES: To prospectively
      compare the diagnostic utility of home-based nasal airflow and oximetry to
      attended polysomnography (PSG) and to assess the diagnostic value of adding
      oximetry to nasal airflow for OSA. DESIGN: Cross-sectional study. SETTING:
      Laboratory and home. PARTICIPANTS: Sleep clinic patients with suspected OSA.
      INTERVENTIONS: All patients had laboratory PSG and 2 sets of 3 consecutive nights
      on each device; nasal airflow (Flow Wizard, DiagnoselT, Australia) and oximetry
      (Radical Set, Masimo, USA) at home in random order. RESULTS: Ninety-eight of the
      105 patients enrolled completed home monitoring. The accuracy of nasal airflow
      respiratory disturbance index (NF RDI) was not different from oximetry (ODI 3%)
      for diagnosing OSA (area under the ROC curve (AUC) difference, 0.04; 95% CI of
      difference -0.05 to 0.12; P = 0.43) over 3 nights of at-home recording. The
      accuracy of NF RDI was higher after 3 nights compared to one night (AUC
      difference, 0.05; 95% CI of difference, 0.01 to 0.08; P = 0.04). Addition of
      oximetry to nasal airflow did not increase the accuracy for predicting OSA
      compared to nasal airflow alone (P > 0.1). CONCLUSIONS: Nasal flow and oximetry
      have equivalent accuracy for diagnosing OSA in the home setting. Choice of device
      for home screening of sleep apnea may depend on logistical and service delivery
      issues.

PMID- 20815195
TI  - Changes in serum TSH and free T4 during human sleep restriction.
AB  - STUDY OBJECTIVES: To examine whether recurrent sleep restriction is accompanied
      by changes in measures of thyroid function. DESIGN: Two-period crossover
      intervention study. SETTING: University clinical research center and sleep
      laboratory. PARTICIPANTS: 11 healthy volunteers (5F/6M) with a mean (+/- SD) age
      of 39 +/- 5 y and BMI 26.5 +/- 1.5 kg/m2. INTERVENTION: Randomized exposure to 14
      days of sedentary living with ad libitum food intake and 5.5- vs. 8.5-h overnight
      sleep opportunity. MEASUREMENTS AND RESULTS: Serum thyroid-stimulating hormone
      (TSH) and free thyroxine (T4) were measured at the end of each intervention.
      Partial sleep restriction was accompanied by a modest but statistically
      significant reduction in TSH and free T4, seen mainly in the female participants
      of the study. CONCLUSIONS: Compared to the well-known rise in TSH and thyroid
      hormone concentrations during acute sleep loss, tests obtained after 14 days of
      partial sleep restriction did not show a similar activation of the human thyroid
      axis.

PMID- 20815196
TI  - [Genetic diversity of Polygonum capitatum from Guizhou populations by ISSR
      markers].
AB  - OBJECTIVE: To detect genetic diversity of 48 population of Polygonum capitatum in
      Guizhou province. METHOD: The genetic diversity of 48 representational
      populations of P. capitatum including 240 individuals had been investigated by
      ISSR marker technique. RESULT: The genetic diversity had been revealed as follow:
      A total of 8 293 bands were produced in 240 individuals, of which 7 962 bands
      were common in the 48 population. The value of the average percentage of
      polymorphic bands (PPB) was 79.09%, Nei's genetic diversity index (H(e)) was
      0.245 8, Shannon's information index (I) was 0.396 2, and genetic differentiation
      index (G(st)) was 0.238 0 at population level, respectively. The genetic
      differentiation index (G(st)) was 0.072 2, genetic differentiation coefficient by
      Shannon's diversity (I(st)) was 0.044 2 within the population levels. Groups
      cluster analysis based on the UPGMA method indicated that although the 48
      populations could be divided into 3 groups and the P. capitatum seed sources. The
      groups cluster showed that a cross clustering of P. capitatum between the
      southwest and southeast populations in Guizhou province, and no significant
      correlation was found between geographical and genetic distance among them.
      CONCLUSION: The genetic diversity of P. capitatum is relatively high at the
      population levels, while low within the population levels, a significant degree
      of genetic differentiation occurs among the populations. The groups cluster
      analysis indicated they has not apparent genetic variation in regional pattern
      between the place of origin populations and the migrate populations.

PMID- 20815197
TI  - [Numerical taxonamy of Paris plants].
AB  - Numerical taxonomic studies were carried out in order to elucidate the taxonomic
      relationship among 17 species belonging to Paris. Eighteen characters including
      10 morphological, 4 pollen morphological, 2 cytotalonomical and 2 habitat
      characters were used for the analysis. On basis of UPGMA clustering analysis, two
      subgenus and seven groups were recognized. The classification of the two subgenus
      was different from the opinion of subgenus Daiswa and subgenus Paris by Li Heng.
      The classification of sect. Dunnianae, sect. Axiparis and sect. Paris was
      correspondence with the classification of Li Heng. But sect. Fargesianae, sect.
      Marmoratae and sect. Thibeticae which were established based on the especially
      characters by Li Heng were put into cluster 2, cluster 3 and cluster 4.

PMID- 20815198
TI  - [Effects of different storage methods on germination and physiological indexes of
      seed-stem of Pinellia ternata from Sichuan].
AB  - OBJECTIVE: To study the optimum storage methods of Pinellia ternata from Sichuan.
      METHOD: Nine methods were used to overwintering storage of the seed-stem of P.
      ternata from Sichuan. The germination of seed-stem was observed through the
      following year after planting, then the germination percentage, vigor of
      germination and germination index were calculated. At the seedling stage, the
      physiological indexes like rooting number, root length, root activity,
      chlorophyll content and catalase activity etc. were determined. RESULT: Under the
      different storage conditions, all the tested indexes of P. ternata from Sichuan
      were significantly different between each other (P < 0.05), except the
      chlorophyll content. CONCLUSION: The seed-stem of P. ternata from Sichuan should
      be preserved in the wet sand (or in soil) in a greenhouse or 4 degrees C
      refrigerator. Under these conditions, the germinating vigor and growth activity
      of seed-stem performed the best.

PMID- 20815199
TI  - [Changes of total RNA and mRNA differential expressions in leaves of Pinellia
      ternata under high temperature stress].
AB  - OBJECTIVE: To study the total RNA and mRNA differential expression in leaves of
      Pinellia ternata under high temperature, provide more information of the
      molecular mechanism of the sprout tumble. METHOD: The total RNA and mRNA
      differential expression in leaves of P. ternata at different stress time was
      analyzed. RESULT: The results showed that the trend of total RNA content was
      divided into three descending stages and two ascending stages, the total RNA
      content was the highest at 0, 6 h, but it was the lowest at and 42 h, as well as
      when the sprout tumbled. The differential display showed that the polymorphism
      and type of bands of the sample at 6 h were similar to those at 0 h. But the
      bands numbers at other time were far less than those at 0, 6 h. And there were
      some different mRNA differential expression bands between the different samples.
      CONCLUSION: In the process of the sprout tumble caused by high temperature
      stress, the RNA and mRNA differential expression in leaves of P. ternata changed.

PMID- 20815200
TI  - [Research and investigation in germplasm resource of Dendrobium chrysotoxum].
AB  - Collected and preserved germplasm resource of Dendrobium chrysotoxum to lay the
      foundation for screening fine germplasm. Through refering literatures, visiting
      and field survey to investigate the distribution, botanic characters and apply
      status of D. chrysotoxum, furthermore to collect the germplasm resource. The
      result show that wild germplasm resource of D. chrysotoxum has obvious
      differences in stem characters, leaf shape as well as flower color aspects. In
      addition, in recent ten years, the reserves of D. chrysotoxum germplasm resource
      seriously descended. Through this study, we can draw a conclusion that D.
      chrysotoxum germplasm resource exist diversity in biology. In these germplasm
      resource, there are high yield and good quality variety.

PMID- 20815201
TI  - [Effects of nitrogen application levels on yield and active composition content
      of Desmodium styracifolium].
AB  - OBJECTIVE: To find out the optimal nitrogen application level of Desmodium
      styracifolium. METHOD: A field experiment using randomized block design was
      carried out to study the effects of 5 nitrogen application levels (150, 187.5,
      225.0, 262.5 and 300.0 kg x hm(-2)) on yield and active component content of D.
      styracifolium. RESULT: Nitrogen application could increase the yield and contents
      of polysaccharide, total flavonoides and total saponins of D. styracifolium.
      However, the enhancing extent of the active component content and the yield were
      not always significant with the increase of nitrogen level. In which, the yield
      were not significantly different among the nitrogen application levels of 225.0,
      262.5, 300.0 kg x hm(-2) the polysaccharide content was no significantly
      difference among the nitrogen application levels of 225.0, 262. 5 and 300.0 kg x
      hm(-2), the total flavonoides content under the nitrogen level of 300.0 kg x hm(
      2) was significantly lower than that of 150.0 kg hm(-2) (P < 0.01), and the total
      saponins content under the nitrogen level of 300.0 kg x hm(-2) was no significant
      difference compared with that of 262.5 kg x hm(-2). CONCLUSION: The optimal
      nitrogen application level of D. styracifolium was 225.0-262.5 kg x hm(-2).

PMID- 20815202
TI  - [Sequence analysis of rDNA-ITS of Bai Shouwu from different species].
AB  - OBJECTIVE: To study the genetic diversity of rDNA ITS sequences in different
      species of Bai Shouwu, utilize the molecular diversity of ITS sequences to
      authenticate the different species of Bai Shouwu. METHOD: Firstly, total DNA was
      extracted from the different species of Bai Shouwu. Secondly, the ITS sequence
      was amplified by PCR with universal primer of ITS and sequenced after cloning and
      purification. RESULT: From four species the complete sequence of ITS and 5.8 S
      rDNA, the partial sequences of 18S rDNA and 26S rDNA were obtained. The rDNA ITS
      sequences of Cynanchum bungei (sign in No. GU198970 and No. GU479037) were
      obtained. Ten variable sites among the sequences were found. CONCLUSION: ITS
      sequence could be used to authenticate the species. The method could be used to
      identify germplasm resources and authenticate.

PMID- 20815203
TI  - [Comparative study on dissolution of Xianlinggubao capsules prepared by different
      processes].
AB  - OBJECTIVE: To study the dissolution characteristics of seven active components of
      Xianlinggubao capsules in vitro, and compare the dissolution of Xianlinggubao
      capsules prepared by different processes. METHOD: The dissolution of
      Xianlinggubao capsules was determined by small cup method with the rotating speed
      of 100 r x min(-1) and phosphate buffer (pH 6.8) as dissolution medium. The
      different dissolution rates in vitro of seven kinds of active components
      (icariin, epimedin C, asperosaponin VI, psoralen, isopsoralen, salvianolic acid B
      and tanshinone IIA) of Xianlinggubao capsules were investigated. The contents of
      active components were determined by HPLC. The accumulative dissolution
      percentages were calculated, and the resemblance of release curves were compared
      by similarity factors (f2). RESULT: The results of determination showed that the
      similarity factor values (f2) of the dissolution curves of seven active
      components after different preparation processes were all less than 50.
      CONCLUSION: There is significant difference in dissolution of active components
      between Xianlinggubao capsules of different preparation processes. The
      accumulative dissolution percentages of the active components in new
      Xianlinggubao capsules are higher than that of Xianlinggubao capsules.

PMID- 20815204
TI  - [HPLC fingerprint spectrum of honey-fried Radix Glycyrrhizae].
AB  - OBJECTIVE: To establish the HPLC fingerprint of the pieces of honey-fried Radix
      Glycyrrhizae. METHOD: Using the reverse-performance liquid chromatography, method
      was performed on a Hyperclone ODS C18 column (4.6 mm x 250 mm, 5 microm) and
      acetonitrile-0.1% phosphoric acid was selected as mobile phase gradient elution
      were adopted. RESULT: Established HPLC fingerprint of Radix et Rhizoma
      glycyrrhizae pieces were established, and the results of methodological study met
      the technical requirements for fingerprinting. CONCLUSION: The HPLC method is
      stable, accurate, and reliable to provide a scientific basis of quality control
      standard for the honey-fried Radix et Rhizoma glycyrrhizae.

PMID- 20815205
TI  - [Quality control and discrimination of angelica different processed products
      based on HPLC fingerprints combined chemometrics methods].
AB  - OBJECTIVE: To establish a chemical fingerprint method for reorganizing and
      validating angelica different processed products. METHOD: A high-performance
      liquid chromatographic method was developed to establish the fingerprint.
      Principal component analysis, hierarchical cluster analysis and discriminate
      analysis were applied to study HPLC finger printing and chemical pattern
      reorganization. RESULT: There were difference of characteristic peaks and its
      relative peak area of HPLC fingerprints between different processed products.
      Fish's discriminate functions were generated by using six selected predictor
      variables, the tested samples of different processed products were classified
      with 100% accuracy, and discriminate analysis plots for the five groups were well
      resolved. CONCLUSION: The developed HPLC finger print, combined with
      chemometrics, can accurately identify and validate angelica different processed
      products, the research provide theoretical basis for the processing mechanism and
      quality assess of angelica different processed products.

PMID- 20815207
TI  - New isoprenylated flavonoid from Morus alba.
AB  - Sanggenol P (1), a new isoprenylated flavonoid, together with nine known ones,
      cyclomorusin (2), morusin (3), mulberrofuran G (4), sanggenol A (5), sanggenol L
      (6), sanggenol N (7), cyclomulberrin (8), cyclocommunol (9) and ursolic acid (10)
      was isolated from Morus alba L. Sanggenol P (1) was characterized based on
      extensive IR, UV, 1D and 2D NMR spectroscopic analysis. Compounds 5, 6, 7 and 9
      were obtained from this plant for the first time.

PMID- 20815206
TI  - [Processing mechanism of calamine].
AB  - OBJECTIVE: The aim of this study is to analyze the processing mechanism of
      calamine. METHOD: XRD, TEM and IR were adopted to analyze the structures and the
      components of original and calcined calamine. Their antibacterial activities were
      also determined. RESULT: The results indicated that zinc carbonate in original
      calamine was decomposed into zinc oxide after processing at 700 degrees C for 1
      hour using original calamine of 40 mesh, and the particle size was smaller than
      before processing. All of ZnO, ZnCO3 and Zn5 (CO3) 2 (OH) 6 had antibacterial
      activitives. CONCLUSION: Original calamine is deposed to ZnO after being calcined
      for 1 h at 700 degrees C and wet milling. The content of ZnO and antibacterial
      activity of calcined calamine are better than those of original calamine,
      moreover, the particle size diminishes and become dimensional uniformity, and the
      contents of dissolved impurities is decreased. The antibacterial activitives of
      original and calcined calamine are decided by zinc.

PMID- 20815208
TI  - [Glycosides of roasted seeds of Cassia obtusifolia].
AB  - OBJECTIVE: To study the chemical constituents of the roasted seeds of Cassia
      obtusifolia, and to illuminate the change of its effective components before and
      after being roasted. METHOD: The compounds were isolated and repeatedly purified
      by macroporous resin, silica gel column chromatography. Their structures were
      elucidated by physical and chemical properties and NMR data. RESULT: Three
      components were obtained from ethanol extract, and the structures were identified
      as nor-rubrofusarin-6-O-beta-D-(6'-O-acetyl) -glucopyranoside (1), 1-desmethyl-
      aurantio-obtusin-2-O-beta-D-glucopyranoside (2), obtusin (3). CONCLUSION:
      Compounds 1 and 2 were isolated from the roasted seeds of C. obtusifolia for the
      first time, and compound 1 was a new compound.

PMID- 20815209
TI  - [Chemical constituents of roots of Saposhnikovia divaricata].
AB  - OBJECTIVE: To study the chemical constituents in the dried roots of Saposhnikovia
      divaricata. METHOD: The chemical constituents were isolated by various column
      chromatographic methods and structurally elucidated by IR, UV, MS and NMR
      evidences. RESULT: Eighteen compounds were obtained and identified as 3'-O
      angeloylhamaudol (1), isobergapten (2), imperatorin (3), pentacosane acid (4),
      anomalin (5), decursin (6), 5-methoxy-7-(3,3-dimethylallyl- oxy)coumarin (7),
      decursinol angelate (8), xanthotoxin (9), bergapten (10), tectochrysin (11),
      scopoletin (12), hamaudol (13), ledebouriellol (14), cimifugin (15), sec-O
      glucosylhamaudol (16), 4'-O-beta-D-glucosyl-5-O-methylvisamminol (17), and prim-O
      glucosylcimifugin (18). CONCLUSION: Compounds 2, 6-8, and 11 were isolated from
      the roots of S. divaricata for the first time. Compounds 1 and 13-18 were
      chromones, 2, 3, 5-10 and 12 were coumarins, 4 was fatty acid, and 11 was
      flavonoid.

PMID- 20815210
TI  - [Chemical constituents from Parthenocissus quinquefolia].
AB  - The chemical constituents of Parthenocissus quinque were investigated. The
      chemical constituents were isolated by column chromatography on silical gel and
      sephadex LH-20. Their structures were elucidated on the basis of spectral
      analysis and of comparison of physical constant. Nine compounds were isolated
      from this plant and the structures of them were identified as 3,4,5-trihydroxy-
      benzoic acid (1), piceatannol (2), resveratrol (3), resveratrol trans
      dehydrodimer (4), cyphoste mmin B (5), pallidol (6), cyphostemmin A (7),
      quercetin-3-O-alpha-L-rhamnoside (8), myricetin-3-O-alpha-L-rhamnoside (9),
      respectively. Compounds 1, 4-9 were isolated from this plant for the first time.

PMID- 20815211
TI  - [Xanthones of Comastoma pedunlulatum].
AB  - The xanthones in the ethyl acetate extract of Comastoma pedunlulatum were
      investigated. The chromatographic and spectroscopic techniques were used to
      isolate and identify the constituents. Nine xanthones were isolated from the
      active parts of the ethyl acetate portion of the 70% ethanolic extract of C.
      Pedunlulatum, which possess the protective activity against hepatocyte damage
      caused by DL-GalN, and identified as 1,8-dihydroxy-2,6-dimethoxyxanthone (1), 8
      hydroxy-1,2,6-trimethoxyxanthone (2), 1,6,8-trihydroxy-2-methoxyxanthone (3), 1,8
      dihydroxy-3,5-dimethoxyxanthone (4), 1-hydroxy-3,5,8-trimethoxyxanthone (5), 1 
      hydroxy-3,7-dimethoxyxanthone (6), 1,2,6,8-tetrahydroxyxanthone (7), 1,3,7
      trihydroxy4- methoxyxanthone (8), 6,8-dihydroxy-1, 2-dimethoxyxanthone (9). Among
      them, compounds 6-9 were isolated from the genus Comastoma for the fist time.

PMID- 20815212
TI  - [UPLC-Q-TOF-MS analysis of naringin and naringenin and its metabolites in rat
      plasma after intragastrical administration of alcohol extract of exocarpium Citri
      grandis].
AB  - OBJECTIVE: To analyze naringin, naringenin and its metabolites in rat plasma
      after intragastric administration of exocarpium Citri grandis alcohol extract.
      METHOD: Rat blood samples were collected 1.0 hour after oral administration of 50
      g x kg(-1) exocarpium Citri grandis alcohol extract and analyzed by UPLC-Q-TOF
      with MS(E) function. The post-acquisition data were processed using Metabolynx.
      RESULT: Naringin (M1), naringenin (M2), naringin-5-O-glucuronide (M3), naringin-4
      O-glucuronide (M4), glucuronide conjugate of naringenin (M5), naringin-4-O
      sulfate (M6), methylated conjugate of hydroxylated naringenin (M7), glucuronide
      and sulfate conjugate of naringenin (M8), glucuronide conjugate of hydroxylated
      naringenin (M9) in rat plasma were detected. M3, M4, M6 were first reported as
      the metabolites of naringin. M7, M9 were first reported as the metabolites of
      naringenin. CONCLUSION: The results indicated that naringin, naringenin can be
      metabolited as the forms of glucuronidation, sulfation and naringenin can also be
      metabolited as the forms of methylation with hydroxylation and glucuronidation
      with hydroxylation in vivo after administration.

PMID- 20815213
TI  - [Experiment study about effect of Yinqiao detoxifcation oral liquid on natural
      killer cells and TNF-alpha, TGF-beta1 of BALB/C nude mouse infected by influenza
      virus].
AB  - OBJECTIVE: To explore the effect of Yinqiao detoxifcation oral liquid on activity
      of natural killer cells (NK) and serum content of TNF-alpha, TGF-beta1 of BALB/C
      nude mouse infected by influenza virus. METHOD: To establish infected mice model
      by FM1 followed by intragastric administration of Yinqiao detoxifcation oral
      liquid for treatment. LDH method was used to observe NK cells. ELISA method was
      used to determine the levels of TNF-alpha, TGF-beta1, in serum on 1st, 3rd, 5th,
      7th days after infection. RESULT: Comparing to the normal group, the NK activity
      of the model group was significantly increased on 1 dpi (day post infection), and
      significantly decreased on 3, 5, 7 dpi. The NK activity of three dosage groups
      (5, 10, 20 g x kg(-1)) of Yinqiao detoxifcation oral liquid were respectively
      higher than that of the model on 3, 5, 7 dpi, especially with high dose (P <
      0.01). The serum level of TNF-alpha and TGF-beta1 of model group is higher than
      that of normal group on 1, 3, 5, 7 d. Compared with model group, the serum level
      of Yinqiao detoxifcation oral liquid groups (5, 10, 20 g x kg(-1)) were decreased
      in different degree on every time point, especially the serum level of the higher
      dose of Yinqiao detoxifcation oral liquid decreased on 3 dpi (P < 0.05), Yinqiao
      detoxifcation oral liquid inhibit the serum level of TGF-beta1 in a dose
      dependent manner. CONCLUSION: Yinqiao detoxifcation oral liquid could enhance the
      activity of NK cell and decrease the serum level of TNF-alpha and TGF-beta1 of
      the mice infected by influenza virus.

PMID- 20815214
TI  - [Adjustment effects of Herba epimedii, Fructus ligustrilucidi on NO/ET, HPA axis
      in asthmatic rats].
AB  - OBJECTIVE: To study the neuro-endocrine adjustment effects of Herba Epimedii and
      Fructus Ligustrilucidi on the asthmatic rats. METHOD: Rat asthma model was
      duplicated by OVA (ovalbumin) through sensitizing and challenging. Fifty male
      rats were randomly divided into normal group, model group, adjustment group of
      Herba Epimedii and Fructus Ligustrilucidi, Peibenfang group and Asimei capsule
      group. Investigating levels of ET (Endothelin), NO, iNOS (inducible NOS ), and
      cNOS (constitutive NOS) in blood serum and BALF (bronchoalveolar lavage fluid ),
      CORT (corticotrophin) in serum, ACTH (adrenocorticotropin hormone) in plasma, CHR
      (corticotropin release hormone) in hypothalamus, protein expression of GCR
      (glucocorticoid receptor) in lung tissue. RESULT: The adjustment of Herba
      Epimedii and Fructus Ligustrilucidi could inhibit ET and NO content in BALF (all
      P < 0.05), decrease the level of iNOS in serum and BALF (P < 0.01 or P < 0.05),
      and increase the level of cNOS in serum and BALF (P < 0.01 or P < 0.05), raise
      the concentration of serum CORT (P < 0.01), enhance the protein expression of GCR
      in lung tissue (P < 0.05). CONCLUSION: The preventive and therapeutic effect of
      Herba Epimedii and Fructus Ligustrilucidi on asthma relates to their adjustment
      effect on ET/NO and HPA axis.

PMID- 20815216
TI  - [Expression changes of age-related genes in different aging stages of
      Caenorhabiditis elegans and the regulating effects of Chuanxiong extract].
AB  - OBJECTIVE: To explore the expression changes of age-related genes in different
      stages of aging and the regulating effects of Chuanxiong extract on it. METHOD:
      According to the different stages of aging, the experiments were tested at two
      time points of 2 d and 6 d. Using realtime RT-PCR (qRT-PCR) to test the
      expression change of aging-related genes among the groups. RESULT: Compared with
      the 2 d control group, the expression of age-1, daf-2, let-363 were up-regulated
      in the 6 d control group (P < 0.05) while the expression of ins-18, let-60, sir
      2.1, sod-3 were down-regulated (P < 0.05). Compared with the 2 d administration
      group, the expression of age-1, daf-2, let-363 were significantly up-regulated (P
      < 0.01) in the 6 d administration group after treated with CXE while the
      expression of ins-18, let-60, sir-2.1, sod-3 were significantly down-regulated (P
      < 0.01). CONCLUSION: In the progress of aging, the expression of age-1, daf-2,
      let-363 increased, functioning as aging-promoting genes; while the expression of
      ins-18, let-60, sir-2.1, sod-3 decreased, functioning as longevity genes; CXE
      extended the lifespan through inhibiting the expression of these aging-promoting
      genes and increasing the expression of longevity genes, which would be the
      molecular mechaniSm of anti-aging of traditional Chinese medicine that can
      promote Qi and activate blood.

PMID- 20815217
TI  - [Material and mechanisms induced pseudo allergic reactions of Yuxingcao
      injection].
AB  - OBJECTIVE: To investigate the characteristics, sensitizin and the mechanism of
      pseudo allergic reaction induced by Yuxingcao injection. METHOD: Beagle dogs were
      randomly assigned to control group, 0.5% tween 80 group, Yuxingcao injection
      without tween 80 group, Yuxingcao injection included 0.5% tween 80 group. The
      animals in control group were intravenously injected with saline. The other group
      were intravenously injected with the corresponding test substances. Observe
      pseudo anaphylaxis of Beagle dogs within 30 min after administration. Blood
      pressure and respiration rate of Beagle dogs were measured before and after
      injection drugs 10 min and 30 min respectively. The pseudo allergic reactions
      were scored at same time points, and the sera of animals were collected to
      determine the HIS, CH50 and C5b-9 concentration using ELISA. RESULT: The scores
      of allergic reaction in 0.5% tween 80 group and Yuxingcao injection included 0.5%
      tween 80 group was evidently higher than that in control group in 2-5 min after
      administration. Animals of above two groups showed the symptoms of red swelling
      on ear part, pruritus, throwing the head, nausea, lapping the tongue, dysphoria
      and bradykinesia. Some of them had behaved with repose, urination, defecation,
      cyanosis, the frequency of breathes accelerating and blood pressure decreasing.
      The rate of pseudo allergic reactions was 100%. Serum CH50 concentration of 0.5%
      tween 80 group decreased 10 min after injection, while C5b-9 concentration
      increased. No obvious differences were observed 30 min after injection. There was
      no significant difference in HIS concentration between control group and
      treatment groups. CONCLUSION: The pseudo allergic reactions appeared after
      intravenous 0.5% tween 80 and Yuxingcao injection when mixed with tween 80.
      Furthermore, Yuxingcao injection without tween 80 did not induce pseudo allergic
      reactions. It was suggested that the pseudo allergic reactions of Yu Xing Cao
      Injection was related to the cosolvent tween 80. The pseudo allergic reactions of
      tween 80 may relate to the activation of complement.

PMID- 20815215
TI  - [Effects of ingredients from Chinese herbs with nature of cold or hot on
      expression of TRPV1 and TRPM8].
AB  - OBJECTIVE: To study the effects of the ingredients from Chinese herbs with the
      nature of cold or hot on the expression of TRPV1 and TRPM8. METHOD: The effects
      of ingredients from herbs on primary culture DRG neurons are observed in vitro.
      The expression quantity of gene is detected by the method of real time PCR. the 2
      (-deltadeltaCT) method is applied to analyze the data. RESULT: Ingredients from
      herbs with the nature of cold up-regulate the expression level of TRPV1 and down
      regulate that of TRPM8, especially under the temperature condition of 39 degrees
      C; while ingredients from herbs with the nature of hot up-regulate the expression
      level of TRPM8 and down-regulated that of TRPV1, which is more significant under
      the temperature condition of 19 degrees C. CONCLUSION: The regulatory changes of
      TRPV1 and TRPM8 mRNA expression induced by the chemical ingredients might be
      related to the cold and hot natures of the herbs from which the ingredients are
      extracted. And this could be one of the therapeutic mechanisms for the treatment
      of Chinese herbal medicines to cold- and heat-related diseases.

PMID- 20815218
TI  - [Inhibitory effect on estrogen production and its influence on invasive ability
      of human endometrial cells of endometriosis by medicated serum of SLW].
AB  - OBJECTIVE: To study the inhibitory effect of medicated serum of SLW on estrogen
      production and to approach on the key mechanism of SLW in inhibiting the invasion
      ability of endometrial cells of endometriosis. METHOD: First, the model of
      eutopic primary cultured endometrial cells of endometriosis and hysteromyoma in
      vitro was successfully established. Taking that of endometrial cells of
      hysteromyoma as control, the secretion level of E2 of endometrial cells in the
      culture media supernatant at different time point with the treatment of high,
      middle and low dose of SLW serum was detected by electrochemiluminescence
      immunoassay, the activities of matrix metalloproteinase-2, 9 (MMP-2, 9) were
      detected by gelatinase zymography assay, and the expression of tissue inhibitor
      of metalloproteinase-1, 2 (TIMP-1, 2) protein was observed by immunofluorescence.
      After the optimal time for SLW to inhibit invasion ability of endometrial cells
      was identified based on time-effect relationship, another endometrial cells were
      divided into six groups: hysteromyoma endometrium group, eutopic endometrium of
      endometriosis group, eutopic endometrium of endometriosis + middle dose of SLW
      serum group, eutopic endometrium of endometriosis + middle dose of SLW serum + E2
      group, eutopic endometrium of endometriosis + anastrozole serum group , and
      eutopic endometrium of endometriosis + E2 group. The activities of MMP-2, 9 and
      the expression of TIMP-1, 2 protein were detected according to the optimal time
      point. RESULT: The secretion level of E2 of eutopic endometrium in endometriosis
      could be decreased by SLW, which showed the dependence of time and concentration.
      The result of gelatinase zymography assay and immunofluorescence respectively
      showed that along with the time the activities of MMP-2, 9 of eutopic endometrial
      cells of endometriosis were significantly higher than those of hysteromyoma at
      the same time point (P < 0.01). After 48 hours, with the treatment of middle dose
      of SLW serum, the activities of MMP-2, 9 of eutopic endometrial cells of
      endometriosis could be decreased (P < 0.01) while the expression of TIMP-1, 2
      protein could be increased obviously (P < 0.01). The malignant invasion ability
      improved by SLW of eutopic endometrial cells of endometriosis was partly
      recruited by add-back E2 treatment. There was no significant difference in the
      activity of MMP-2 and the expression of TIMP-1, 2 protein between eutopic
      endometrium of endometriosis + middle dose of SLW serum + E2group and untreated
      group. The behavior of invasion of endometrial cells of endometriosis could be
      deteriorated treated by E2 as contrast to anastrozole, a specific aromatase
      inhibitor. CONCLUSION: SLW could decrease the secretion of E2 so as to inhibit
      the invasion of the eutopic endometrial cells of endometriosis.

PMID- 20815219
TI  - [Effects of Panax notoginseng saponins on immune-neuroendocrine network of SD
      rats in experimental navigation and intensive exercise].
AB  - OBJECTIVE: The present study aims to study the influences experimental navigation
      and intensive exercise on immune-neuroendocrine network of the male rats and the
      effects of PNS to this influence. METHOD: Thirty 6-week Sprague-Dawley male rats
      (SD rats) were randomly located into three groups: Quiescent control (QC) group,
      training control (TC) group and Panax notoginseng saponins (PNS) group. Rats from
      QC group were not given any stimuli, and samples were taken after 7-day
      intragastric administration of saline. Rats from TC group underwent 10-day run
      training of increasing load on treadmill and received 7-day intragastric
      administration of saline. PNS group were subjected to the same procedure of run
      training as group TC, and received intragastric administration of PNS at the dose
      of 0.2 g x kg(-1). Blood samples were immediately obtained at the end of the
      tests to determine the serum levels of corticosterone (Cort), adrenocorticotropic
      hormone (ACTH), beta-endorphin (beta-EP), Neuropeptide Y (NPY) and interleukin
      1beta (IL-1beta), interleukin-6 (IL-6) by RIA. Expressions of Pituitary ACTH, NPY
      were observed use the immunohistochemistry method and correlation analyses
      conducted. And the ultrastructural changes of the pituitaries and the adrenal
      cortex cells were examined by electron microscope meanwhile. RESULT: The serum
      beta-EP and Cort levels in TC group were significantly increased compared to the
      QC group; whereas Expression levels of pituitary ACTH, NPY were markedly higher
      after experimental navigation and intensive exercise. In Group PNS, the plasma
      Cort, ACTH and NPY levels decreased significantly compared to Group TC. Meanwhile
      we found expression levels of pituitary ACTH, NPY also lower than group TC. There
      was no significant difference about the ultrastructure of anterior pituitary and
      adrenal cortex of QC and PNS group. However, a obvious change of ultrastructure
      occurred to TC group rats. CONCLUSION: These results suggest that immune
      neuroendocrine network function of rats were confused by negative psychological
      stresses and intensive exercise. PNS therapy may exert regulation effects to the
      network.

PMID- 20815220
TI  - [Effect of Chaihu Shugan Tang on excitability in different brain regions of
      pentylenetetrazole-kindled chronic epileptic rats].
AB  - OBJECTIVE: To study the effect of the Chinese compound prescription Chaihu Shugan
      Tang (CHSGT) on the excitability in the cerebral cortex and hippocampus
      (different brain regions) of pentetrazole (PTZ)-kindled chronic epileptic rats.
      METHOD: To establish the model of chronic kindling rats intraperitoneal injected
      with pentylenetet. Fully kindled rats were randomized into control and
      experimental groups for intragastric administration of normal saline (control,
      model), Sodium Valproate and CHSGT at the high, medium and low doses for 4
      consecutive weeks. The content of 2-NBDG, the glutamate (Glu) and the aspartate
      (Asp) in different brain regions of rats were detected by fluorescence imaging
      techniques and HPLC assay respectively. RESULT: CHSGT at the high, medium and low
      doses all significantly decreased the content of 2-NBDG, the Glu and the Asp in
      different brain regions of chronic epileptic rats (P < 0.01). CONCLUSION: CHSGT
      can inhibit the excitability in different brain regions of PTZ-induced epileptic
      rats, by decreasing the level of excitatory neurotransmitter maybe one of its
      antiepileptic mechanisms.

PMID- 20815221
TI  - [Effect of Ruiqi tablet on mitochondrion activities in cerebral cortex neurons of
      fetal rats].
AB  - OBJECTIVE: To explore the effect of Ruiqi tablet on mitochondrion activities in
      the cerebral cortex neurons of fetal mice. METHOD: The cerebral cortex of fetal
      Wistar rats after 16- 17 gestation days were collected and randomized into Ruiqi
      tablet group and blank control group after 4-5 days' culture. Laser scanning
      confocal microscope was adopted to determine the changes in the mitochondrion
      activities of the primary cultured cerebral cortex neurons of fetal rats after
      addition of Ruiqi tablet solution. RESULT: Ruiqi tablet can increase the
      mitochondrion activities of the cerebral cortex neurons. No significant change in
      the mitochondrion activities of the cerebral cortex neurons was found in the
      blank control group. CONCLUSION: Ruiqi tablet can increase the mitochondrion
      activities of the neurons and it has certain application prospects in treatment
      of some neurodegenerative diseases such as Alzheimer's disease, vascular
      dementia, Parkinson's disease and so on.

PMID- 20815222
TI  - [Ingredients of Shuanghuanglian injection powder permeation through placental
      barrier of rat in pregnancy].
AB  - OBJECTIVE: Use HPLC to study the permeation of ingredients of Shuanghuanglian
      injection powder (SHL) through placental barriers of rats at different stages of
      pregnancy. METHOD: The pregnant rats were administered SHL for 5 d through
      caudalis vena at different stages of pregnancy. Plasma and embryonic tissues were
      obtained 12 h after the final administration of SHL. The componds in biological
      specimen were identified by HPLC. RESULT: Baicalin, luteolin and wogonoside were
      the main compounds in plasma. Wogonoside retained in first trimester embryonic
      tissues, and baicalin retained in the embryonic tissues of different pregnant
      stages. CONCLUSION: Baicalin is the main compound of SHL through placental
      barriers of rats. Embryotoxicity of baicalin should be considered as the key
      point to evaluate the safety of SHL.

PMID- 20815223
TI  - [Textual study of ginseng in Wupu Bencao].
AB  - In the study of materia medica literature, we found of ginseng in Wupu Bencao
      that "Leaf is a little sharp, root is black and stem is pilous" had been ignored
      by its subsequent literatures. In this study, the variety of ginseng in Wupu
      Bencao was researched. We believed the remaining records of ginseng in Wupu
      Bencao referred to Oplopanax elatus instead of Panax ginseng. The origin of this
      species was in Handan during the period of three-kingdom dynasty, but distributed
      in the area of Changbai mountain nowadays.

PMID- 20815224
TI  - [Development of alpha-glucosidase inhibitor from medicinal herbs].
AB  - Alpha-glucosidase inhibitor can reduce the postprandial hyperglycemia and have
      good effect on preventing and treating the diabetes and diabetic complication.
      Along with the application of acarbose which is a kind of alpha-glucosidase
      inhibitor, many research groups pay attention to the crude alpha-glucosidase
      inhibitor screened from the medicinal herbs in order to find new, safe, and
      effective medicine. The development of alpha-glucosidase inhibitor screened from
      the medicinal herbs and its evaluation in vivo and vitro as well as the varieties
      of the medicinal herbs that contain alpha-glucosidase inhibitor in recent 30
      years were summarized in this paper.

PMID- 20815225
TI  - [Thought on several problems of clinical revaluation of post-marketing herb
      research].
AB  - The revaluation of post-marketing herb is a complex research work, which concerns
      widely content and difficult to put it into practice. The starting of our
      country's revaluation post-marketing herb was comparatively late. It should
      profect it both in laws and regulations mechanism as well as technological
      specification. This article is try to focus on some attention problems in
      revaluation of postmarketing herb process. Such as the laws and regulations
      demand, the basement and the subject of revaluation of post-marketing herb.

PMID- 20815226
TI  - [Technical standards of traditional Chinese medicine industry].
AB  - Basing on the basic theory of traditional Chinese medicine (TCM), the technical
      standards of TCM industry is such a Link that it is to clarify the internal
      relations between the basic theory of TCM and developing of TCM industry. This
      article analyzed several problems of technical standards of TCM industry, such as
      basic theory of TCM and standardization problem of TCM industry. Technical
      standards of TCM industry must receive the guidance of basic theory of TCM, so
      that it will promote the process of modernization and internationalization of TCM
      industry.

PMID- 20815227
TI  - [A diterpenoid quinone from Periploca forrestii].
AB  - Tanshinone II A, which was known unique to the salvia, was separated and purified
      by silica gel column chromatography and recrystallisation from an ethyl acetate
      soluble portion (the anti-inflammatory active portion) of ethanol extract of
      Periploca forrestii. The diterpenoid quinone was obtained from the Periploca for
      the first time.

PMID- 20815228
TI  - [Taxonomy and pathogenic mechanism of Cronobacter (Enterobacter sakazakii)--a
      review].
AB  - Enterobacter sakazakii is an important food-borne pathogen that causes life
      threatening meningitis and necrotizing colitis in neonates and children. In 2008,
      Enterobacter sakazakii has been reclassified as five species in a new genus,
      Cronobacter gen. nov. within the Enterobacteriaceae. There is the variation in
      virulence between species in the new genus. OmpA of Cronobacter gen. nov. plays a
      critical role in attachment to their host cell and persistence within
      macrophages. Disruption of the tight junction significantly enhances the
      efficiency of invasion. Specific probiotic strains and their combinations
      counteract adhesion of Cronobacter gen. nov to intestinal mucus. At present, very
      limited information is available regarding the pathogenesis of Cronobacter gen.
      nov. Further detailed mechanism studies on the pathogenicity are warranted.

PMID- 20815229
TI  - [Progress of research on the microbial fuel cells in the application of
      environment pollution treatment--a review].
AB  - Microbial fuel cells (MFCs) are bio-electrochemical reactors that have the
      capacity to convert chemical energy of biodegradable organic chemicals to
      electrical energy, and developed rapidly in the past few years. With an
      increasing concern for energy crisis and environment pollution, MFCs has became a
      promising technology in the researches of environment pollution treatments and
      biology electricity. In this paper, we offered a comprehensive review of the
      recent research progress of MFCs in environment pollution treatment, includes
      denitrification, desufurization, organic pollutants degradation, heavy metal
      reduction and landfill leachate treatment. Also, we pointed out the challenges
      and problems which were bottle necks for a wide application of MFCs and the
      potential future development.

PMID- 20815230
TI  - [Screening and identification of plant growth-promoting rhizobacteria].
AB  - OBJECTIVE: The interaction between plant growth promoting rhizobacteria (PGPR)
      and plants can be unstable, PGPR with PGP activities may be well adapted to
      particular soil environment. Based on this, we isolated and identified PGPRs from
      different rhizosphere soils according to their multiple mechanisms. METHODS:
      Preliminary screening of PGPRs under the premises of PGPR may having the
      abilities of N2-fixing, phosphate and potassium solubilization, and resistance
      against six common pathogenic fungi as well as rhizosphere colonization. After
      that, multiple PGP activities were detected in vitro. Finally, PGPRs were
      classified and identified by combining physiological and biochemical tests and
      16S rRNA gene sequence analysis. RESULTS: Fourteen strains having various
      mechanisms of PGP activities such as NH3, IAA, HCN, siderophore, antibiotics
      production, phosphate and potassium solubilization, and N2-fixing were isolated
      from different rhizosphere soils in Yangzhou and Yancheng, Jiangsu province.
      These 14 isolates could be identified as Pseudomonas (7 isolates), Paenibacillus
      (3 isolates), Bacillus (2 isolates), Burkholderia (1 isolate) and Erwinia (1
      isolate). CONCLUSION: Isolates with multiple PGP activities can also be
      rhizospheric competent, able to survive and colonize in the rhizosphere,
      providing promising isolates for PGPRs combination to resolve the challenges in
      field application of PGPR.

PMID- 20815231
TI  - [Actinobacterial diversity of marine sediment samples from Chile].
AB  - OBJECTIVE: The aim of this study was to investigate actinobacterial diversity in
      Chilean marine sediments. METHODS: Actinobacterial diversity in these sediments
      was investigated by selective isolation method, culture-independent method and
      phylogenetic analysis based on 16S rRNA gene sequences. Six selective media were
      used to isolate actinomycetes from sediment samples. The primers for the class
      Actinobacteria were used for Actinobacterial 16S rRNA gene amplification and then
      a clone library was constructed for the sediment sample btt. Twenty-two strains
      with different culture characteristics and 59 clones from sample btt were
      selected for 16S rRNA gene sequences analysis. To determine requirement for
      seawater each strain was grown on oatmeal agar prepared with deionized water and
      with seawater, respectively. Strains were screened for antibiotic activity
      against bacteria and fungi. RESULTS: In total 328 actinomycetes were obtained.
      Twenty-two strains which were selected belonged to Streptomyces, Micromonospora,
      Polymorphospora, Aeromicrobium and Brachybacterium. Fifty-nine clones (40 OTUs)
      were sequenced, and 60% OTUs belonged to Actinobacteridae, Acidimicrobidae and
      Rubrobacteridae. The other 40% OTUs, which formed several distinct clades in
      phylogenetic tree among phylum Actinobacteria may represent new taxonomical
      groups. 50% of the 47 sea water dependant strains and nineteen strains out of the
      above 22 strains exhibited antimicrobial activity. CONCLUSION: There was abundant
      actinobacterial diversity in the marine sediments of Chile, and the result
      implied that there were large numbers of unknown actinobacterial groups in the
      sediments. Actinomycetes from Chilean marine sediments had the potential of
      producing bioactive secondary metabolites.

PMID- 20815232
TI  - [Screening of three straw-cellulose degrading microorganism].
AB  - OBJECTIVE: The aim of this study was to screen straw-cellulose degrading
      microorganisms and to investigate their degradation ability of straw-cellulose.
      METHODS: The methods used to screen the high effect straw-cellulose degrading
      microorganism included the traditional isolation methods of straw-cellulose
      degrading microorganism such as holes observation method on filter paper sheet,
      disintegration test of filter paper scrip, hydrolysis spot diameter measurement
      method of CMC-Na, weight lose assay method of straw, measurement method of
      cellulose decomposition rate, measurement method of extracellular enzyme
      activity. RESULTS: We isolated 3 fungi with cellulose degrading ability, of which
      98MJ was identified as Penicillium oxalicum, W3 as Trichoderma sp., and W4 as
      Penicillium expansum. Strain W4 possessed high straw-cellulose degrading ability
      with straw-cellulose degrading rate of 56.3%, cellulose 59.06%, hemicellulose
      78.75% and lignin 33.79% in 10 days. CONCLUSION: Strain W4 was a cellulase
      producing strain with broad development potential.

PMID- 20815233
TI  - [Correlation between endogenous hydrogen peroxide and mesosome formation in
      cellular injured bacteria].
AB  - OBJECTIVE: Ultrastructural alteration and hydrogen peroxide (H2O2) localization
      were examined in Xanthomonas under cellular injury using transmission electron
      microscopy. METHODS: Histochemical methods were used in the present study.
      RESULTS: Intriguingly, the injury led to presence of an additional location of
      H2O2 accumulation within the cells. There was an association between the
      frequency and size of the additional location of H2O2 accumulation and the
      degrees of injury. Furthermore, an additional ultrastructure, mesosomes, was also
      present in injured cells. The frequency and size of mesosomes also increased with
      the increasing degrees of injury. CONCLUSION: Result of multiple linear
      regression showed that the size of mesosome plays as a key factor in the quantity
      of excess H2O2 accumulation in bacteria under cellular injury. Linear correlation
      was confirmed between quantity of excess H2O2 accumulation and the size of
      mesosome in injured cells. This finding intensely indicated that mesosomes are
      just the additional location of H2O2 accumulation in cells under cellular injury.
      The excess H2O2 accumulation in mesosomes should be a positive regulatory
      mechanism in bacteria under cellular injury.

PMID- 20815234
TI  - [Identification, culture optimization and biotransformation of a stevioside
      degrading bacterium].
AB  - OBJECTIVE: Our study aimed at screening and identifying a specific bacterium
      capable of degrading stevioside. We also studied the conditions of enzyme
      production and stevioside conversion. METHODS: Taxonomic group of the strain was
      confirmed by physical characterization and phylogenetic analysis by 16S rRNA gene
      sequence analysis and phylogenetic tree construction of the strain. The optimum
      conditions of enzyme producing and stevioside degrading were studied by single
      factor and multi-factor statistical analysis. Degradation product was detected
      and identified via liquid chromatography-mass spectrometry. RESULTS: Based on the
      result of 16S rRNA gene sequence analysis, the strain named J2 shares 100%
      sequence identity with the sequence of the Bacillus megaterium. The activity of
      beta-Glucosidase produced by this Bacillus megaterium strain was up to 779.68
      U/ml with 4% maize starch, 1% defatted soybean, 0.04% MgSO4 and 0.2% stevioside
      as culture medium when fermented under the condition of pH 7.0, 37 degrees C, 220
      r/min and 10% inoculum for 36 h. The results of conversion showed that 10 mg/ml
      stevioside can be converted to steviolbioside by 74% after 3 days which has been
      identified by LC-MS. The ratio of rebaudioside A and stevioside was increased to
      0.99 compared to original solution 0.38, which lead to 160.5% increasement of
      rebaudioside A in the relative amount. Stevioside can be converted completely
      after 5 days. CONCLUSION: The isolated strain J2 was identified as Bacillus
      megaterium. It was a novel and safe strain with high, specific conversion
      stevioside to steviolbioside ability.

PMID- 20815235
TI  - [Cloning, expression and characterization of a novel esterase from marine
      sediment microbial metagenomic library].
AB  - OBJECTIVE: To clone, express and characterize a novel esterase from marine
      sediment microbial metagenomic library. METHODS: Using esterase segregation agar
      containing tributyrin, we obtained esterase positive fosmid clone FL10 from
      marine sediment microbial metagenomic library. This fosmid was partially digested
      with Sau3A I to construct the sublibrary, from which the esterase positive
      subclone pFLS10 was obtained. The full length of the esterase gene was amplified
      and cloned into the expressing vector pET28a, and the recombinant plasmid was
      transformed into E. coli BL21 cells. We analyse the enzyme activity and study the
      characterization of the esterase after its expression and purification. RESULTS:
      An ORF (Open Reading Frame) of 924 bp was identified from the subclone pFLS10.
      Sequence analysis indicated that it showed 71% amino acid identity to esterase
      (ADA70030) from a marine sediment metagenomic library. The esterase is a novel
      low-temperature-active esterase and had highest lipolytic activity to the
      substrate of 4-nitrophenyl butyrate (C4). The optimum temperature of the esterase
      was 20 degrees C, the optimum pH was 7.5. The esterase in this study had good
      thermostability at 20 degrees C and good pH stability at pH8 -10. Significant
      increase in lipolytic activity was observed with addition of K+ and Mg2+, while
      decrease with Mn2+ etc. CONCLUSION: We obtained the novel esterase gene fls10
      from the marine sediment microbial metagenomic library. The esterase had good
      thermostability and high lipolytic activity at low temperature and under basic
      conditions, which laid a basis for industrial application.

PMID- 20815236
TI  - [Cloning and expression of prenyl transferase gene of Metarhizium ansopliae].
AB  - OBJECTIVE: To clone and identify prenyl transferase gene from Metarhizium
      anisopliae and to understand the gene structure and expression. METHODS: Using
      Switching Mechanism At 5' end of RNA Transcript (SMART) method, we isolated the
      full length cDNA sequence and DNA sequence. Then we used quantitative RT-PCR
      analysis of the gene expression levels at different stages of colonization of
      host hemolymph by M. anisopliae. RESULTS: The Mpt gene had two exons and one
      intron and the CDS was 1026 bp which encoded a protein with 341 amino acid
      residues; qRT-PCR analysis showed that the gene expression levels were
      significantly different, especially highly up-regulated at the late stages.
      CONCLUSION: The Mpt gene was successfully cloned from M. anisopliae for the first
      time and the gene had the characteristic of high expression levels at the late
      stages.

PMID- 20815237
TI  - [Scl1 of M41-type group A streptococcus binds low-density lipoprotein].
AB  - OBJECTIVE: To study the interaction of streptococcal collagen-like protein 1
      (Scl1) of M41-type group A streptococcus (GAS) ATCC12373 with low-density
      lipoprotein (LDL). METHODS: We cloned, expressed and purified the recombinant
      proteins rScl1 and its V region rScl1-V, designated as C176 and C176V, derived
      from Scl1. 41 of M41-type GAS. The binding of rScl1 to LDL was detected with
      affinity chromatography-binding assay, Western blot analysis and enzyme-linked
      immunosorbent assay (ELISA), and whole cell binding assays were used to detect
      the interactions of whole GAS cells with LDL. RESULTS: The results demonstrated
      that C176 and C176V could specifically bind purified LDL, and M41-type GAS cells
      expressing native Sell could bind LDL whereas M6-type GAS could not. CONCLUSION:
      The Sell of M41-type GAS specifically binds LDL.

PMID- 20815238
TI  - [Diversity of bacteria associated with pine wood nematode revealed by
      metagenome].
AB  - OBJECTIVE: The pine wood nematode (PWN), Bursaphlenchus xylophilus, which
      collaborates with its associated bacteria to form ecosystem and has interaction
      among them, is the pathogen of pine wilt disease. This study focused on revealing
      the bacterial diversity of ecosystem of pine wood nematode and its associated
      bacteria. METHODS: The metagenome of ecosystem of bacteria associated with the
      PWN was analyzed by 16S rRNA gene library and 454 sequencing. RESULTS: The
      results showed that 25 OTUs (Operational Taxonomic Units) were obtained from the
      library according to sequences similarity of 97%, which affiliated to
      Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria and Bacteroidetes.
      The dominant bacteria were belonged to Gammaproteobacteria, especially
      Stenotrophomonas maltophilia in this class dominated the library. In terms of
      dominant bacteria, the results revealed by metagenome were similar to that of 16S
      rRNA gene library. CONCLUSION: The diversity of bacteria associated with the PWN
      is high and these bacteria maybe have ecological role to the PWN.

PMID- 20815239
TI  - [Flocculating activity of Penicillium purpurogenum EL-02 and its flocculating
      activity].
AB  - OBJECTIVE: To isolate, identify and characterize a fungus with flocculating
      activity. METHODS: We used gradient dilution, plaque distribution and 18S rDNA
      analysis to isolate and identify a fungus with flocculating activity. We used
      high-speed centrifugation, ultrasonication and qualitative test to determine the
      nature of flocculating active substances. RESULTS: We isolated a flocculating
      active fungi and identified it as Penicillium purpurogenum. Ultrasonication test
      confirmed that the flocculating activity was primarily in the fermentation
      supernatant. We explored the flocculating activity curve and found that 4 days
      was the optimum fermentation time for accumulating flocculating active
      substances. The strain flocculating activity remains unchanged when pH varied
      from 2 to 11 and temperature varied from -70 degrees C to 100 degrees C. We
      finally identified the flocculating active substances as saccharides. CONCLUSION:
      We isolated a flocculating active strain P. purpurogenum EL-02, and identified
      its flocculating active products as saccharides.

PMID- 20815240
TI  - [Analysis of microbial community structure in mangrove sediments by PCR-DGGE
      technique].
AB  - OBJECTIVE: To understand the microbial community in mangrove sediments. METHODS:
      Sixteen stations were established in the Fugong mangrove area of Jiulong River
      Estuary, Fujian, China. Microbial community structure in this area was evaluated
      by PCR-DGGE method. The genetic diversity of microorganisms was analyzed based on
      the DGGE fingerprint. RESULTS: There were significant differences among the
      Shannon-wiener index, Richness and evenness. The possible reason might due to
      distinct location of samples from different stations. Bacterial diversity was
      higher in the mangrove areas than that in non-mangrove areas. Similarity analysis
      of bacterial communities in different station showed certain trends in similarity
      coefficients, and bacterial community structure similarity of the same transect
      was much higher than others. According to the results of sequence analysis of
      DGGE dominant bands, all of them were phylogenetically close to Proteobacteria,
      Acidobacteria and Chlorobia which belonged to uncultured microbes from coastal
      sediments in the estuary. CONCLUSION: There are abundant microbial diversity and
      a large number of unknown microbial resources in mangrove sediments which need
      further research.

PMID- 20815241
TI  - [Expression, purification, and characterization Mycobacterium tuberculosis
      Rv1168c].
AB  - OBJECTIVE: To express and purify the Pro-Pro-Glu (PPE) family protein Rv1168c of
      Mycobacterium tuberculosis in E. coli. and to study the structure of Rv1168c.
      METHODS: The Rv1168c gene was amplified by PCR from Mycobacterium tuberculosis
      H37Rv strain genomic DNA and cloned into a prokaryotic expression vector pET32a
      The resulting recombinant expression plasmid pET32a-Rv1168c was then transformed
      into the E. coli strain DH5alpha and a high-level expression E. coli BL21(DE3)
      was established after induction with Isopropyl-beta-D-thiogalactopyranoside
      (IPTG). SDS-PAGE and mass spectrum analysis determined the relative molecular
      weight of this recombinant Rv1168c protein. It's secondary and 3D structures were
      determined by circular dichroism and homologous modeling. RESULTS: The
      Mycobacterium tuberculosis Rv1168c gene (971bp) and high purified recombinant
      Rv1168c protein was obtained. The relative molecular weight of recombinant
      Rv1168c protein was determined to be 51.5 kDa (vector included). Secondary
      structure of Rv1168c had about 34.4% alpha helix, 33.7%, beta tune, 31.9% random
      coil at 25 delta C. Homologous modeling shows Rv1168c as (beta/alpha)5 protein.
      CONCLUSION: This study obtained purified recombinant Rv1168c protein and laid the
      foundation for exploration of the relationship between the structure and function
      of Rv1168c in the tuberculosis.

PMID- 20815242
TI  - [Detection and sequences analysis of sheep hepatitis E virus RNA in Xinjiang
      autonomous region].
AB  - OBJECTIVE: To understand whether hepatitis E virus (HEV) was infectious in sheep
      in Xinjiang. METHODS: We used reverse transcription-nested polymerase chain
      reaction(RT-nPCR) to detect HEVRNA in feces. The feces were collected from sheep
      with positive anti-HEV antibodies in a sheep farm in Xinjiang Autonomous Region.
      RESULTS: Six of 54 (11.11%) sheep were positive for HEV RNA. PCR amplification
      products were cloned, sequenced and analyzed. The homology among HEV of the 6
      sheep HEV ORF2 189bp nucleotide amplification sequences was 99.38%-100%. They
      should belong to the same genotype. They were respectively compared with HEV
      genotype I, II, III and IV corresponding 189bp nucleotide sequences. The average
      homology was 78.67%-85.33%, 81.33%-82.67%, 78.67%-84.00% and 84.67%-95.36%. The
      maximum homology between 6 nucleotide amplification sequences and one sequence of
      genotype IV was 94.04%-95.36%. Based on sequence of the nucleic acid fragments, a
      phylogenetic tree was constructed. Six sheep HEV ORF2 189bp nucleotide
      amplification sequences in this study and bovine HEV, swine HEV and human HEV
      locate the same evolutionary vine and belong to genotype IV. CONCLUSION: The
      finding suggested that infection of HEV probably exists in the sheep group in
      Xinjiang Autonomous Region and the sheep may be a new animal host except swine in
      origins of HEV infection.

PMID- 20815243
TI  - [Evaluation the immuno-protective effect of an infectious clone of meq- deleted
      Marek's disease virus].
AB  - OBJECTIVE: To evaluate the immuno-protective effect of GX0101 deltameq-BAC
      containing an infectious meq-null Marek's disease virus genome. METHOD: One-day
      old SPF birds were reared separately in isolators with positive filtered air. On
      day 1 of age, chickens immunized with 101 microg of GX0101A deltameq-BAC
      suspended in PBS, challenge infection with 500PFU very virulent rMD5 was
      performed at day 5 and 12 post-immunization separately. During 90 days after
      challenge, all bird were recorded and checked for necropsy. The samples of heart
      and liver were collected for histo-sections. RESULTS: The protective index of the
      two vaccines used was 87 and 33 for CVI988/Rispens and GX0101 deltameq-BAC,
      respectively, after challenged with the very virulent virus rMd5 at day 5 post
      immunization. When challenged with rMd5 at day 12 post-immunization, the
      protection index of GX0101 deltameq-BAC increased to 53%. CONCLUSION: Except that
      GX0101 deltameq-BAC can confer protection against very virulent Marek's disease
      virus, a delay in the development of Marek's disease could be observed in some
      chickens vaccinated with GX0101 deltameq-BAC. On the other hand, compared with
      CVI988/Rispens, the reconstruction of GX0101 deltameq-BAC in the body is a
      prerequisite for access to protection. Therefore, there is a blank period after
      immunization, which provides a chance for infection with the wild Marek's disease
      virus.

PMID- 20815244
TI  - [Effect of polyethylene glycol as adjuvant on hepatitis B virus DNA vaccine in
      vitro].
AB  - OBJECTIVE: To explore whether polyethylene glycol (PEG) as adjuvant could enhance
      the humoral and cellular immune responses on hepatitis B virus DNA vaccine.
      METHODS: C57BL/6J mice were immunized with PEG and pVAX-S2 or alone pVAX-S2.
      After these mice were finally immunized for 14 days, the anti-HBs IgG, T cell
      proliferation, the expression of cytokines and CTL in vivo were detected.
      RESULTS: Compared to mice immunized with alone pVAX-S2, PEG as adjuvant could
      increase the production of anti-HBs IgG and HBsAg specific T cell proliferation.
      In addition, the expression of IL-4, IFN-gamma in CD4+ T cells and IFN-gamma in
      CD8+ T cells was higher than control groups. The PEG/ pVAX-S2 groups could elicit
      significantly in vivo HBsAg specific CTL responses. CONCLUSIONS: PEG as adjuvant
      could enhance humoral and cellular immune responses, as well as in vivo CTL
      activity.

PMID- 20815245
TI  - [Effect of different culture conditions on carbonic anhydrase from Bacillus
      mucilaginosus inducing calcium carbonate crystal formation].
AB  - OBJECTIVE: Effect of various culture conditions on the morphology, amount and
      carbonic anhydrase (CA) activity of Bacillus mucilaginosus were examined, as well
      as the effect on calcium carbonate crystal forming, shape and amount. METHODS:
      The strain was inoculated in N-free or N-containing medium, and the bacterial
      morphology, number and CA activity were compared under different culture
      conditions. By collecting different cultures and adding them to the system of
      calcium carbonate crystallization we studied the relationship between the
      bacteria and the formation of calcium carbonate crystals. RESULTS: A small number
      of cell, capsular hypertrophy, lower CA activity in bacterial culture were
      obtained under N-free culture condition. In contrast, more biomass quantity, thin
      capsule, and high CA activity were got in the nitrogen-containing culture. In the
      calcium carbonate crystal system, adding N-free culture of bacteria produced a
      smooth surface of calcium carbonate crystals, larger volume but small density,
      the addition N-containing culture of bacteria formed rough surface, bigger
      density but smaller volume of calcium carbonate crystals. CONCLUSION: Different
      culture conditions can cause significant differences in bacterial amounts,
      capsular thickness and CA activity, and then influence the crystal growth and
      form of calcium carbonate.

PMID- 20815246
TI  - [Cloning and transcriptional profiling of PsNCS1 from Puccinia striiformis f. sp.
      tritici].
AB  - OBJECTIVE: We cloned PsNCS1 encoding neuronal calcium sensor from Pst and
      analyzed its transcriptional profile. METHODS: A full-length cDNA of PsNCS1 was
      cloned by using RT-PCR in combination with cDNA library screening, the sequence
      was analyzed with different bioinformatic tools and the gene expression pattern
      was characterized via real-time RT-PCR. RESULTS: PsNCS1 (Genbank accession no.
      GU134621) encoded 190 amino acids, with a molecular weight of 22.17 KDa and a pI
      of 4.96. PsNCS1 contained four conserved EF-hand domains and was N-terminally
      myristoylated. Phylogenetic analysis indicated that PsNCS1 was highly similar to
      the NCS from Basidiomycetes and the highest similarity was with that from
      Puccinia graminis (96%). Real-time RT-PCR analysis indicated the amount of PsNCS1
      transcripts of urediospores and of germinated urediospores were doubled or more
      comparing with those of fungal bodies at other different developmental stages.
      CONCLUSION: PsNCS1 might be involved in the process of urediospore formation and
      germ tube elongation. The present results may provide basic data for further
      analysis of the role of PsCNS1 in pathogenesis process and calcium signaling.

PMID- 20815247
TI  - [Gene cloning, codon optimization and functional expression of Yarrawia
      lipolytica lipase Lip1].
AB  - OBJECTIVE: To implement inducible and constitutive over-expression of Yarrowia
      lipolytica lipase gene lipl in Pichia pastoris using codon optimization. METHODS:
      We cloned Y. lipolytica lipase gene lip1 according to codon bias of P. pastoris,
      and optimized lipl using overlap extension PCR synthesis. Then, we cloned the
      original and optimized genes into the induced vector pPIC9K and newly built
      constitutive carrier pGAP9K, and electrotransformated the resultant expression
      plasmids into P. pastoris GS115. Through G418 resistance screening, high copy
      transformatants were selected and fermented in shake flasks. P-nitrophenyl
      palmitate (pNPP) was used as substrates for assay the activities of the expressed
      lipase, and the characteristics of the lipase were further examined. RESULTS: We
      successfully cloned lipase gene lip1 from Y. lipolytica, nucleotide sequence
      revealed that the open reading frame (ORF) had 1461 nucleotides, encoding 486
      amino acids, without any intron or any signal peptide. SDS-PAGE analysis and
      fermentation result showed that the optimized gene had a higher expression level
      than the original one, and the constitutive expression was superior to the
      inducible expression. Preliminary analysis showed that the optimal substrate of
      Lipl was p-nitrophenyl butyrate (C4), the optimum temperature and pH was 45
      degrees C and 8.5, respectively. CONCLUSION: Y. lipolytica lipase gene lip1 can
      be over-expressed through both inducible and constitutive expressions using codon
      optimization, which lays a solid foundation to further study Y. lipolytica lipase
      family, and also provides an important prerequisite for scale production and
      industrial application of the lipase.

PMID- 20815248
TI  - [From human genome to man-made life: J. Craig Venter leads the life sciences].
AB  - For the first time ever, the scientists of J. Craig Venter team have created
      actual self-replicating synthetic life. The research was just published in the
      Journal of Science on May 20, 2010. Although this news immediately brings the
      worry about the possible potential threat to biosecurity and biosafety as well as
      the ethical disputes, it yet indicates that mankind have made a new step forward
      in synthetic biology. In the time of post-genome era, we believe the advancement
      of synthetic biology that might affect or change the future life of human being
      will be widely used in energy, environment, materials, medication and many other
      fields.

PMID- 20815249
TI  - [Progress in application of targeting viral vector regulated by microRNA in gene
      therapy: a review].
AB  - A safe and effective targeting viral vector is the key factor for successful
      clinical gene therapy. microRNA, a class of small, single-stranded endogenous
      RNAs, act as post-transcriptional regulators of gene expression. The discovery of
      these kind regulatory elements provides a new approach to regulate gene
      expression more accurately. In this review, we elucidated the principle of
      microRNA in regulation of targeting viral vector. The applications of microRNA in
      the fields of elimination contamination from replication competent virus,
      reduction of transgene-specific immunity, promotion of cancer-targeted gene
      therapy and development of live attenuated vaccines were also discussed.

PMID- 20815250
TI  - [Structure and function of heavy metal transporter P(1B)-ATPase in plant: a
      review].
AB  - The regulation of the heavy-metal accumulation in vivo for plant survival is very
      complex. The metal cation transporter plays key roles in the metabolic process.
      P(1B)-ATPases are the only subgroup of P-ATPases that contribute to heavy metal
      homeostasis presented in most organisms. Arabidopsis thaliana contains eight
      genes encoding P(1B)-ATPases. The current reports show that the functions of
      P(1B)-ATPases are involved in maintaining metal homeostasis, transporting and
      detoxification in plants. P(1B)-ATPases not only mediated metal ion mobilization
      and uptake in roots, but also contribute to the metal transport, storage and
      tolerance in shoots, especially in heavy metal hyperaccumulators. In this paper,
      we reviewed and discussed the evolution, classification, structure and function
      of P(1B)-ATPases in plants. HMAs-transgenic manipulation could be a feasible
      approach for phytoremediation and mineral nutrition fortification.

PMID- 20815251
TI  - [Recent advances in bacterial biodegradation of naphthalene, phenanthrene by
      bacteria: a review].
AB  - Polycyclic aromatic hydrocarbons (PAHs) are toxic pollutants that exist
      extensively in the environment. Microbial degradation is the main pathway of PAHs
      eradication in natural environment and therefore is of importance to investigate.
      Advancement has been made in recent years regarding the PAHs molecular
      degradation mechanisms in bacteria. In this review, we summarized some of the
      research progresses in microbial PAHs biodegradation pathways (including
      salicylate pathway and protocatechuate pathway), key enzymes (nah-like, phn, phd,
      nid and nag) and genes involved. Emphasis was given on naphthalene and
      phenanthrene which were often used as the representatives of PAHs. It is likely
      that the new information will promote further research and applications of
      microbial PAHs biodegradation technology.

PMID- 20815252
TI  - [Improving fatty acid composition and increasing triacylglycerol content in
      plants by gene engineering: a review].
AB  - This article reviewed key genes that involved in fatty acid synthesis and
      triacylglycerol assembly pathway. The transcription factors which play important
      roles in seed development and oil content were also reviewed. We summarized the
      achievement in modifying fatty acid composition and increase oil content in plant
      by gene engineering using these genes.

PMID- 20815253
TI  - [Effect of ascorbic acid, epidermal growth factor and follicle stimulating
      hormone on in vitro culture of sheep ovarian cortical tissue].
AB  - In this study, we evaluated the effects of ascorbic acid (VC), epidermal growth
      factor (EGF) and follicle stimulating hormone (FSH) on in vitro culture of sheep
      ovarian cortical tissue. Using 2 x 2 x 2 factor experimental design, we cultured
      sheep ovarian cortex fragments in 8 media with MEM (control), MEM+VC (50
      microg/mL), MEM +EGF (100 ng/mL), MEM+FSH (50 ng/mL), MEM+VC+EGF, MEM+VC+FSH,
      MEM+EGF+FSH, MEM+VC+EGF+FSH. After 0 (non-cultured control), 2, 6, 12 days of
      culture, the pieces of ovarian cortex were proceed to histological and
      proliferating cell nuclear antigen (PCNA) examination, or observed by
      transmission electron microscopy (TEM). The percentages of developing follicles
      were increased (P < 0.05) and the percentages of healthy follicles were reduced
      (P < 0.05). When compared to the MEM group, the addition of FSH with VC or EGF
      promoted a significant increase of follicles diameter and follicles survival rate
      (P < 0.05), and stimulated the proliferation of granulosa cells. After 12 days of
      culture, medium supplemented with MEM+VC+EGF resulted the lowest proportion of
      developing follicles (49.3% +/- 3.2%), follicles diameter((32.3 +/- 2.3) microm),
      follicles survival rate (41.6% +/- 3.1%) and the proportion of PCNA stained
      follicles (26.4% +/- 1.2%, P < 0.05). In contrast, MEM+VC+EGF+FSH resulted the
      highest follicles diameter ((42.5 +/- 5.1) microm), follicles survival rate
      (59.7% +/- 6.1%) and proportion of PCNA stained follicles (43.5% +/- 4.1%, P <
      0.05). Ultrastructural analysis confirmed the integrity of follicles cultured in
      VC+EGF+FSH group, while follicles cultured in MEM+VC+EGF groups showed more
      degeneration characters. In conclusion, the addition of VC and EGF to culture
      medium inhibited follicular development, VC+EGF+FSH was the most effective
      treatment to maintain follicular integrity and promote sheep primordial
      follicular activation and growth during in vitro culture.

PMID- 20815254
TI  - [Preparation and characterization of specific monoclonal antibodies against
      mercury ions].
AB  - The environmental pollution by heavy metals such as mercury, cadmium and lead has
      become a worldwide public health hazard. To rapidly and inexpensively monitor
      environmental heavy metals is a prerequisite for minimizing human and animal
      exposure. The development of immunoassays to detect mercury ion residues has been
      a promising trend with the advantage of rapid and cheap operation. We reported
      the isolation and characterization of mercury-specific monoclonal antibodies.
      Because Hg2+ ions are too small to elicit an immune response, the metal was
      coupled to protein carrier (keyhole limpet, KLH) using a chelator
      (diethylenetriamine pentaacetic acid, DTPA). After the synthesis of antigen and
      characterization, monoclonal antibodies against mercury ions were generated by
      immunizing BALB/c mice with mercury conjugated antigen (Hg-DTPA-KLH). The stable
      hybridoma cell lines were produced by fusion of murine splenocytes and SP2/0
      myeloma cells. The hybridoma cells were subcloned by the limiting dilution and
      screened by ELISA, two hybridoma cell lines producing stably specific monoclonal
      antibodies (MAbs) against mercury ions were obtained, named H2H5 and H1H8. The
      ascites fluid was produced in BABL/c mice by intraperitoneal injection of 1 x
      10(7) H2H5 and H1H8 cells, respectively. The titers of ascites were all above
      1:51 200. The isotyping of secrete antibodies from two hybridoma cell lines was
      IgG1, kappa type. These data laid a potency of establishing immunoassays methods
      of determining Hg2+ ion residues and had the realistic significance for improving
      the efficiency and quality of risk assessment.

PMID- 20815255
TI  - [Characterization of the functional domain of STT3a of oligosaccharyltransferase
      from Dunaliella salina].
AB  - To investigate the function of STT3a gene in salt adaptation and flagellar
      regeneration of Dunaliella salina (D. salina), a pair of degenerate primers was
      designed according to conserved homologous amino acid sequences of VCVFTA and
      DVDYVL of STT3a from Chlamydomonas, Arabidopsis thaliana and other organisms. A
      cDNA sequence of 1 650 bp encoding a whole functional domain of STT3a was
      amplified from D. salina by RT-PCR and 3' Rapid Amplification of cDNA Ends
      (RACE), which shared homology with Chlamydomonas (48%), Arabidopsis thaliana
      (50%), Homo sapiens (46%), etc. Real-time fluorescence quantitative PCR (real
      time Q-PCR) demonstrated that the STT3a mRNAs from D. salina were induced by
      increased concentration of NaCl, and increased to 11-fold higher by 3.5 mol/L
      NaCl than that by 1.5 mol/L NaCl (P < 0.01). Also, STT3a mRNA of D. salina
      maintained at a higher level in the process of flagellar regeneration with than
      without experiencing deflagellar treatment. In conclusion, the findings of this
      study demonstrate that the high expression of the STT3a gene enhances the
      capability of salt adaptation and flagellar regeneration in D. salina.

PMID- 20815256
TI  - [Cloning of keratinocyte growth factor 2 gene (KGF2) and its transformation to
      Brassica napus L].
AB  - Recently, more research about the plant bioreactor expressing genes encoding
      human proteins was reported. In the present study, the cDNA of the human gene
      keratinocyte growth factor 2 (KGF2) was replaced with plant preferred codons by
      PCR, and the modified full-length cDNA was cloned into the plant expression
      vector pCAMBIA-YO containing the oil-body promoter. The fusion construct pCAMBIA
      YO-KGF2 was transformed into Brassica napus by Agrobacterium tumefacien-mediated
      cotyledon transformation method. The transgenic seedlings were identified by PCR,
      Southern and western blot analysis all showed that KGF2 gene was successfully
      expressed in in transgenic Brassica napus.

PMID- 20815257
TI  - [Polyethylenimine and minicircle DNA based gene transfer].
AB  - Polyethylenimine (PEI) is one of the most characterized non-viral vectors. It can
      condense DNA in a good manner and achieve high transfection efficiency.
      Minicircle DNA (mc-DNA) is a novel kind of supercoiled DNA which is devoid of
      bacterial backbone. mc-DNA is superior to conventional DNA for its higher
      transfection efficiency and longer time-span. In this study, we combined PEI and
      mc-DNA in gene delivery system. We investigated the physicochemical and
      biochemical effects of this non-viral system and further explore its potential in
      tumor gene therapy. mc-DNA was obtained by recombination of parental plasmid in
      the presence of L-arabinose, and complexed with PEI. The results of transmission
      electron microscopy and scanning electron microscopy showed that the particles
      were spherical and homogeneous. Through gel retardation assay and MTT assay, we
      found that there were no obvious differences in binding capability of PEI to mc
      DNA and plasmid DNA, as well as in cytotoxicity. The results of dynamic light
      scattering showed that the size of PEI/mc-DNA was about 68 nm, a slight larger
      than that of PEI/plasmid DNA. Furthermore, the tumor cells transfected with mc
      GFP showed higher GFP expression level than that of conventional plasmid. The
      same results were achieved in the cells treated with tumor-suppressor gene pten,
      assayed by RT-PCR and Western blot. It indicates that the system of
      PEI/minicircle DNA is promising in gene transfer.

PMID- 20815258
TI  - Enhanced antitumor effect of combining interferon beta with TRAIL mediated by
      tumor-targeting adeno-associated virus vector on A549 lung cancer xenograft.
AB  - Interferon beta (IFN-beta) and TNF-related apoptosis-inducing ligand (TRAIL) are
      effective anticancer agents. Adeno-associated virus (AAV) is one of the current
      most promising gene delivery vectors. Previously, we constructed tumor-targeting
      AAV-hTERT-IFN-beta and AAV-hTERT-TRAIL by inserting IFN-beta or TRAIL gene into
      AAV controlled by hTERT promoter. The studies showed that either single IFN-beta
      or TRAIL gene therapy exhibited a certain extent anticancer effect. Here, we
      report their inhibitory effects on A549 lung cancer cell growth in vitro and in
      vivo by combined AAV-hTERT-IFN-beta and AAV-hTERT-TRAIL. Expression of secreted
      IFN-beta in lung cancer A549 cells infected by AAV-hTERT-IFN-beta was detected by
      enzyme-linked immunosorbent assay (ELISA). The growth-suppressing effect of AAV
      hTERT-IFN-beta in combination with AAV-hTERT-TRAIL on several cancer cell lines
      was assessed by MTT assay. Apoptosis of A549 cancer cells infected by AAV-hTERT
      IFN-beta alone, AAV-hTERT-TRAIL alone, and their combination was evaluated by
      apoptotic cell staining and flow cytometry (FCM), respectively. The antitumor
      effect of the combination of AAV-hTERT-IFN-beta with AAV-hTERT-TRAIL in vivo was
      further evaluated through A549 lung cancer xenograft in nude mice. The results
      showed that the combinational treatment was superior to any alone and presented
      intensified tumor cytotoxic and apoptotic effect on A549 cancer cells. Most
      importantly, the combination of AAV-hTERT-IFN-beta with AAV-hTERT-TRAIL exhibited
      significant antitumor effect and eliminated all tumor masses in nude mice, which
      lay a foundation for exploring the molecular mechanisms of combined IFN-beta and
      TRAIL anti-tumor activity.

PMID- 20815259
TI  - [Improving infection efficiency of adult cynomolgus monkey mesenchymal stem cells
      with lentiviral vectors].
AB  - Mesenchymal stem cells (MSCs) have received considerable attention for various
      therapeutic approaches in recent years. MSCs are also easy to genetically modify
      to express therapeutic genes by using lentiviral vectors. Because of the
      similarities in genetics, physiology and metabolism between non-human primates
      (NHPs) and humans, NHPs models are invaluable for researching human disorders and
      for developing therapeutic strategies. Therefore, MSCs derived from NHPs could be
      a powerful tool for cell therapy and genetic engineering. Studies from captive
      and free-ranging adult NHPs show that up to 100% were infected with simian foamy
      virus (SFV). In this study, we found that all cultured MSCs derived from adult
      cynomolgus monkey were infected with SFV by RT-PCR. Therefore, antiviral drugs
      must be added in MSCs culture. However, because of SFV infection and additive
      antiviral drugs, the infection efficiency of the lentiviral vectors reduced
      significantly. In this study, we improved the infection efficiency by disabled
      antiviral drugs before lentiviral infection. It might be provide technical
      assistance for the culture of adult cynomolgus monkey MSCs as genetically
      engineered cells applied to clinical and experimental research.

PMID- 20815261
TI  - [Transformation of Didymella bryoniae mediated by Agrobacterium tumefaciens].
AB  - Gummy stem blight, a plant disease caused by Didymella bryoniae, is one of the
      major diseases in melon. The disease can seriously reduce melon yield and
      quality. However, little information is available on the genetics and functional
      genomics of the fungal pathogen. In this study, we developed an Agrobacterium
      mediated transformation system for D. bryoniae by using a universal pathogenic
      isolate DB11 and the Agrobacterium tumefaciens strain C58C1 carrying plasmid
      pBIG2RHPH2 harboring the hygromycin B phosphotransferase gene (hph). Total 45
      transformants could be obtained per 1 x 10(5) spores when 1 x 10(6) spores per
      milliliter of D. bryoniae spore suspension were cocultivated with Agrobacterium
      cells at OD600 = 0.15 for 48 h in the presence of induction medium (pH 5.2)
      containing acetosyringone at 200 microg/mL and selection medium contained 100
      microg/mL of hygromycin B and 200 microg/mL of cefotaxime sodium, ampicillin and
      tetracycline, respectively. The transformants were stable when grown on PDA
      medium without hygromycin B for five times and were verified by PCR amplification
      with the hph primers and by Southern blot analysis with the hph probe. The
      transformation system will be useful for further studies of functional genes in
      D. bryoniae.

PMID- 20815260
TI  - [Preparation and verification of antibodies for five rice receptor-like kinases].
AB  - Receptor-like kinase involves self-incompatibility, male sterility, stress
      responses, and disease resistance. To better understand the physiological
      function and biological characteristics of rice receptor-like kinase, we cloned
      five predicted epitope fragments of rice receptor-like kinase. The purified
      fusion protein was used as antigen to immunize rabbit to get specific polyclonal
      antibodies. Western blotting analysis shows that the five receptor-like kinases
      were expressed in rice leaves.

PMID- 20815262
TI  - [A novel method for monitoring miRNA activity by expression changes of secreted
      luciferase gene in live cells].
AB  - We developed a method for monitoring of miRNA activity in live cells by a
      secreted luciferase gene based plasmid sensor named as Gsensor. Firstly, we
      constructed pAAV2neo-Gluc-MCS-polyA as "empty Gsensor", which contained multiple
      cloning sites (MCS) for miRNA target inserted. To detect miR142-3p activity,
      miR142-3p Gsensor and miR142-3p Gsensor-3 were constructed by inserting one or
      three complementary miR142-3p targets into pAAV2neo-Gluc-MCS-ployA. Subsequently,
      miR142-3p Gsensor and miR142-3p Gsensor-3 were respectively transfected into U937
      cells and Gluc activity was assayed in the supernatant 48 h post transfection.
      Results showed that both of them effectively indicated miR142-3p activity of
      inhibiting Gluc expression compared with empty Gsensor. Simultaneously, miR142-3p
      Gsensor also demonstrated the inhibition of miR142-3p activity by Anti-miR142
      when they were cotransfected into U937 cells. This implied one copy of miRNA
      target in Gsensor was sensitive enough for investigation of miRNA activity. We
      further analyzed factors affecting Gsensor function including time and dose, and
      found that miR142-3p activity sensed by miR142-3p Gsensor rose within 48 h post
      transfection and approached stable thereafter. Transfected dose varying among
      0.001-0.05 pg/cell had little effect on its function. Using miR142-3p Gsensor, we
      further detected miR142-3p activity in HEK293, U937, K562, SP2/0 and P815 cells.
      Results suggested that miR142-3p activity was high in U937, K562, SP2/0 and P815
      cells and almost negative in HEK293. miR142-3p activity was positively correlated
      with its relative copies in HEK293, U937 and K562 detected by QRT-PCR. In
      conclusion, Gsensor proved to be an effective tool for monitoring of miRNA
      activity in live cells, and provide a new method for monitoring miRNA activity in
      vitro.

PMID- 20815263
TI  - [SYBR green I real-time polymerase chain reaction for detection of Norovirus II
      in the shellfish].
AB  - We set up an SYBR Green I real-time RT-PCR method for the detection of genogroup
      II Norovirus, and this method's primers were encompassed the conservative region
      of Norovirus II. The limit of the detection was 10(2) copies. The standard
      curve's linear range was 10(2)-10(6) copies, correlation coefficient was 0.9952,
      the slope was -2.982, and the intercept was 35.84. This method possessed
      specificity for genogroup II Norovirus, without any cross-reaction with
      rotavirus, adenovirus, hepatitis A virus or astrovirus. The coefficients of
      variation (CV) of the C(t) values of the standard plasmid were 0.95%-1.69% (n =
      5) in intra-assay and 0.87%-1.24% (n = 3) in inter-assay. We used this method to
      detect 30 shellfish samples, and found 3 samples were positive. This method is
      sensitive, specific and reliable for Norovirus II. It can be used to detect the
      Norovirus II in the shellfish rapidly.

PMID- 20815264
TI  - [Detection of bovine, goat, pig and chicken derived ingredients in animal
      products with universal PCR-microarray method].
AB  - We analyzed the sequence of vertebrate molecular marker genes, then we selected
      the mitochondrial DNA (mtDNA) 16S rRNA gene as marker gene. In order to detect
      four kinds of animal-derived ingredients, which including bovine, goat, pig and
      chicken. We utilized a pair of universal primers, designed four sets of species
      specific microarray probes and two pairs of quality control probes. We optimized
      the PCR amplifications and hybridization conditions, therefore these four kinds
      of animal-derived ingredients could be rapid and accurate detected by this
      approach. The detection limits were all reaches 1 pg. We established the
      detection platform of these four kinds of animal-derived ingredients. This
      universal PCR-microarray assay provides a new method for the identification of
      animal-derived ingredients in the import-export field.

PMID- 20815265
TI  - [Expression of hGM-CSF in transformed silkworm BmN cells mediated by non
      transposon vector].
AB  - To develop the stable transformants of the silkworm (Bombyx mori) BmN cells that
      could continuously express the exogenous gene based on a non-transposon vector,
      an expression cassette containing human granucyto-macrophage colony-stimulating
      factor (hGM-CSF) gene driven by ie-1 promoter from B. mori nucleopolyhedrovirus
      was inserted into pIZT-V5-His to form a recombinant vector pIZT-IE-hGM-CSF,
      followed by transfecting the constructant into BmN cells, the stable ie-hGM-CSF
      cell lines were obtained after being selected with Zeocin. PCR result using the
      genomic DNA of the transformed BmN cells as template illustrated a specific
      fragment of ie-hGM-CSF, and Western blotting analysis using an antibody against
      hGM-CSF demonstrated a specific band with a molecular weight of 22 kDa in the
      transformed cells, meanwhile, the expression level of hGM-CSF determined by ELISA
      was about 2 814.7 pg in 10(6) transformed BmN cells.

PMID- 20815266
TI  - [Expression and characterization of soluble recombinant Ulp1p with glutathione S
      transferase tag in Escherichia coli].
AB  - The aim of the study is to obtain an efficient expression of recombinant
      ubiquitin-like specific protease 1 (Ulp1) by gene engineering. We cloned the
      Ulp1p, active fragment (403 aa-621 aa) of Ulp1, from Saccharomyces cerevisia, and
      subcloned into pGEX/Rosetta (DE3) to form an expression plasmid, pGEX-Ulp1p-His6.
      In order to enhance the solubility of GST-Ulp1p-His6, we purified the fusion
      protein GST-Ulp1p-His6 by either glutathione S-transferase agarose or Ni-NTA
      resin chromatography, the purity was up to 98%. We utilized the protein to cleave
      the SUMO fusions, and the specific activity of GST-Ulp1p-His6 was 1.375 x 10(4)
      U/mg. This study showed that the recombinant protein GST-Ulp1p-His6 displayed
      high specificity and activity.

PMID- 20815267
TI  - [Constitution of knowledge theory system of integrative medicine for disease
      syndrome coupling].

PMID- 20815268
TI  - [Effect of yiqi bushen granule on the peripheral CD4+ CD8high T-lymphocyte and
      natural killer cell in patients with minimal residual leukemia].
AB  - OBJECTIVE: To explore the effect of Yiqi Bushen Granule (YBG) on CD4+ CD8high T
      lymphocyte in patients with minimal residual leukemia (MRL) and to probe its
      prognosis after treatment. METHODS: The changes of CD4+ CD8high T lymphocyte
      subgroup and natural killer (NK) cells in 36 patients (16 males and 20 females)
      received long-term (> 3 months) YBG therapy before and after treatment were
      analyzed using multi-parameter flow cytometry and controlled by those in 34
      healthy persons (19 males and 15 females). RESULTS: The 3-year and 5-year
      complete remission rates in MRL patients were 75.0% and 63.9%; their 3-year and 5
      year survival rates were 80.5% and 72.2%, respectively; as compared with the
      baseline, the absolute value and percentage of CD4+ CD8high T lymphocyte and NK
      cells were all significantly raised after treatment (P < 0.05 or P < 0.01).
      CONCLUSION: YBG could prolong the disease-free survival in MRL patients by way of
      regulating the immune function of organism, elevating the amount of CD4+ CD8high
      T lymphocyte and NK cells to kill or suppress the residual leukemic cell in body.

PMID- 20815269
TI  - [Study on the effect of Yiqi Yangyin Recipe and its different assembling on
      expressions of Flt3 and N-ras in acute myeloid leukemic cells].
AB  - OBJECTIVE: To study the action mechanism of Yiqi Yangyin Recipe (YYR) in treating
      leukemia by observing the effects of YYR and its different assembling, energy
      supporting part (P1) and evil dispelling part (P2) on expressions of Flt3 and N
      ras gene in acute myeloid leukemic (AML) cells. METHODS: The mononuclear cells
      collected from bone marrow of 60 AML patients were assigned to four groups: the
      blank was untreated for control and the three tested groups were treated with
      YYR, P1 and P2, respectively. The effects on Flt3 and N-ras gene expressions and
      FLT3 protein expression were observed by RT-PCR and Western bloting. RESULTS: RT
      PCR test showed the expression of Flt3 in the control, YYR, P1 and P2, group was
      90.78% +/- 6.92%, 38.18% +/- 4.50%, 65.57% +/- 5.55% and 61.35% +/- 6.39%,
      respectively; and that of N-ras in them 93.28% +/- 5.54%, 34.38% +/- 6.69%,
      59.42% +/- 7.35% and 65.28% +/- 7.64%, respectively, both showed significant
      difference as compared the data in the tested groups with those in the control
      group (P < 0.05). Western bloting test showed the FLT3 protein gray value in the
      four groups was 0.8127 +/- 0.0284, 0.4265 +/- 0.0353, 0.5396 +/- 0.0274 and
      0.5473 +/- 0.0282, respectively, also showed significant difference between the
      control and the tested groups (P < 0.01). CONCLUSION: YYR can inhibit the colonic
      proliferation of AML cells, decrease the expressions of FLT3 and N-ras in cells,
      therefore shows a therapeutic effect on AML.

PMID- 20815270
TI  - [Detection and analysis on plasma metabolomics in patient with coronary heart
      disease of Xin-blood stasis syndrome pattern].
AB  - OBJECTIVE: To research the plasmic metabolites and metabolic pathway of Xin-blood
      stasis syndrome (XBSS). METHODS: Plasma metabolic products in patients of
      coronary heart disease (CHD) with XBSS or non-XBSS and subjects in the control
      group were identified by gas chromatographic mass spectrometry (GC-MS) type
      QP2010, the changes of their main elements in different groups were analyzed by
      principal components analysis (PCA) and partial least squares (PLS) analysis.
      RESULTS: PCA showed that as compared with that in the control group, in the CHD
      XBSS group, contents of lactic acid, beta-hydroxy butanoic acid, urea, oleic
      acid, octadecanoic acid and arachidonic acid were higher and that of citric acid
      was lower. PLS analysis showed significant difference between the control group
      and the other two groups, and the latter two groups tend to be of a same
      category. The occurrence of XBSS was positively correlated with octadecanoic
      acid, arachidonic acid, urea, lactic acid and beta-hydroxy, butanoic acid
      contents, and negatively correlated with oleic acid, L-proline, glycine, and
      citric acid contents. According to VIP, the degree of correlation between
      variables with drug interven- tion, from high to low, were ranked as arachidonic
      acid, octadecanoic acid, lactic acid, urea, beta-hydroxy butanoic acid, linoleic
      acid, glucose, alanine, oleic acid and proline. Discrepancy analysis on 11
      changeful metabolites showed that the contents of arachidonic acid, octadecanoic
      acid, lactic acid, urea, beta-hydroxy butanoic acid and oleic acid increased in
      CHD patients, especially in those with XBSS (P < 0.01). In CHD patients, contents
      of lactic acid, beta-hydroxy butanoic acid, linoleic acid and glucose in patients
      of XBSS pattern were higher than in non-XBSS pattern (P < 0.01); content of
      linoleic acid, glucose, alanine and proline decreased in non-XBSS pattern while
      increased in XBSS pattern. Content of glucose in CHD-XBSS patients was
      significantly higher than that in the healthy control (P < 0.01). Content of
      citric acid was lower in CHD patients, and showed significant difference between
      that in CHD-XBSS patients and healthy control (P < 0.01). CONCLUSIONS: The major
      plasmic metabolites in CHD-XBSS patients are arachidonic acid, octadecanoic acid,
      lactic acid, urea, citric acid, beta-hydroxybutyric acid, oleic acid, glucose,
      and alanine. Analyzed from plasmic metabolite spectrum view, CHD-XBSS is related
      with lipid metabolism and glyco-metabolism, also with the stress induced by
      hypoxia and agonia.

PMID- 20815271
TI  - [Using Delphi method to establish diagnostic standard for Xin-blood stasis
      syndrome].
AB  - OBJECTIVE: To provide a reference for quantitative diagnosis of Xin-blood stasis
      syndrome (XBSS) by way of collecting experiences from experts, screening out the
      diagnostic indices and evaluating their significance. METHODS: With Delphi method
      adopted, two rounds of questionnaire survey were carried out in 20 experts, the
      feedback data were statistically analyzed in terms of concentricity, coordination
      and authority using SPSS software. RESULTS: The recovery rates of the two round
      survey were all 100%; the coordinate coefficient was 0.658 in the first round and
      0.622 in the second. And results passed the Chi-square test with P < 0.05, Chi2 =
      189.544 in first round and 235.232 in second round. The average degree of
      expert's authority was 85%. CONCLUSIONS: The enthusiasm and speciality of the 20
      experts were high, and their opinions are of high reliability with great
      coordination. The information entries, including chest pain, stabbing pain, pain
      on a relatively fixed position, chest stuffiness, ecchymosis or petechia on
      tongue, dark-purplish lip and unsmooth pulse, can be taken as the diagnostic
      indices for XBSS sydrome.

PMID- 20815272
TI  - [Effects of Gutuo Qingfu Decoction via gastro-enteric perfusion on 16SrRNA in
      blood of severe multitraumatic patients].
AB  - OBJECTIVE: To observe the effects of Gutuo Qingfu Decoction (GQD) via gastro
      enteric perfusion on blood level of bacterial 16S rRNA gene in severe multi
      traumatic (SMT) patients at early stage. METHODS: Sixty SMT patients were
      assigned to two groups, the 33 in the treated group and the 27 in the control
      group. They were treated with the same conventional treatment, but different in
      the gastro-enteric infusion with GOD for the former and saline for the latter.
      Blood 16SrRNA gene, body temperature, leukocyte count, C-reactive protein (CRP),
      and blood bacterial culture positive rate on the 3, 6, 9 post-trauma days were
      detected, and incidences of infective complication and mortality were observed.
      RESULTS: Body temperature on day 9 in the treated group was significantly lower
      than in the control group (37.6 +/- 0.12 degrees C vs 38.1 +/- 0.15 degrees C, P
      < 0.05); so did the CRP level on day 6 (52.4 +/- 6.3 mg/L vs 104.3 +/- 20.1 mg/L,
      P < 0.05) and day 9 (42.9 + 7.5 mg/L vs 92.5 +/- 17.1 mg/L, P < 0.05), as well as
      the positive rates of blood 16SrRNA gene on day 6 and 9 (33.3% vs 59.3% and 30.3%
      vs 77.8%, P < 0.05 and P < 0.01, respectively). However, the positive rates of
      blood culture were insignificantly different between the two groups ( P > 0.05).
      Besides, incidence of infective complication in the treated group was
      significantly lower than in the control group (30.3% vs 59.3%, P < 0.05).
      CONCLUSION: Early stage gastrointestinal administration of GQD is likely to have
      benefits for the improvement of intestinal mucosa barrier and reduction of
      enteric bacterial translocation in SMT patients, and it may also reduce the
      incidence of infective complication in these patients.

PMID- 20815273
TI  - [Clinical curative effect of Shenxiong Bushen Capsule and its effect on the
      quality of life of patients with Vascular dementia].
AB  - OBJECTIVE: To observe clinical curative effect of Shenxiong Bushen Capsule for
      the treatment of mild vascular dementia (VaD), and probe the partial mechanism.
      METHODS: With a block random, double-blinded and controled clinical research
      method adopted, seventy patients with VaD were randomly assigned to two groups in
      a ratio of 5:2, including 50 cases in the trial group and 20 cases in the control
      group. The patients in the trial group were given the Shenxiong Bushen Capsule (5
      tablets, thrice a day), while those in the control group were given Piracetam (5
      tablets, twice a day). All patients of the two groups were treated for 2 months,
      and one third cases were follow-up surveyed for 1 month. The cognitive ability,
      the activities of daily living, Chinese medicine syndrome of VaD, and the quality
      of life were measured respectively before and after the treatment. RESULTS:
      According to the Mini-Mental State Examination, the clinical effects of patients
      showed that there was insignificant difference between the trial group (total
      effective rate was 74.46% and 80.85%, respectively) and the control group (total
      effective rate was 68.42% and 78.95%, respectively) on the cognitive ability and
      the activities of daily living (P > 0.05), while the curative effect of the trial
      group (total effective rate was 85.11%) was superior to that of the control group
      (total effective rate was 63.16%) on Chinese medicine syndrome of VaD, and had
      significant difference between the two groups (P < 0.05). The results measured by
      WHOQOL-SF36 indicated that the total scores and the scores of each field in both
      the trial group and the control group after treatment increased more than those
      of before treatment (P < 0.01, P < 0.05), except physical function (PF) field and
      role physical (RP) field of the control group (P > 0.05). The scores of the trial
      group about total body, PF field, RP field and vitality (VT) field increased more
      than those of the control group (P < 0.05); while no difference was shown between
      the trial group and control group in the scores of bodily pain field, role
      emotional field, general health field, social function field and mental health
      field (P > 0.05). CONCLUSION: Shenxiong Bushen Capsule has a definite curative
      effect on mild VaD, and it can improve the quality of life of patients. Adopting
      the SF36 Scale to evalute the quality of life of patients with VaD has
      significance and avaibility to some extent.

PMID- 20815274
TI  - [Effect of tripterygium glycosides on serum interleukin-1beta, interleukin-2,
      tumor necrosis factor alpha, and interferon-gamma levels in patients with
      Behcet's disease].
AB  - OBJECTIVE: To investigate the possible mechanism of action of tripterygium
      glycosides (TG) for treatment of Behcet's disease (BD) through observing its
      effect on serum levels of interleukin-1beta (IL-1beta), interleukin-2 (IL-2),
      tumor necrosis factor alpha (TNF-alpha) and interferon-gamma (IFN-gamma).
      METHODS: Thirty primarily treated BD patients (BD group) were treated with TG 30
      mg/d orally for 3 months, and a control group consisting of 30 healthy persons
      was set up. Serum levels of IL-1beta, IL-2, TNF-alpha and IFN-gamma were detected
      by radio-immunosorbent assay (RIA) before and after treatment respectively. And
      the outcomes were analyzed in combining with the clinical status of patients as
      well as related indices as erythrocyte sedimentation (ESR) and C-reactive protein
      (CRP). RESULTS: Serum levels of IL-1beta, TNF-alpha, IFN-gamma in the BD group
      were evidently higher (P < 0.05) than those in the control group, they all
      lowered significantly after 3-month TG treatment, from 10.72 +/- 1.84 microg/L,
      6.64 +/- 1.05 microg/L and 8.93 +/- 1.23 microg/L to 5.71 +/- 1.04 microg/L, 4.27
      +/- 0.76 microg/L and 3.44 +/- 0.72 microg/L, respectively (P < 0.05), while
      level of IL-2 in the BD group was insignificantly different before treatment to
      that in the control (though showed an increasing trend) and was unchanged after
      treatment (P > 0.05). TG treatment showed the effectiveness of markedly effective
      in 10, effective in 16 and ineffective in 4 BD patients, with the total effective
      rate of 86.6%. Besides, ESR and CRP levels were evidently decreased in BD
      patients after treatment (P < 0.05). CONCLUSION: TG may treat BD by way of
      regulating the levels of IL-1beta,TNF-alpha and IFN-gamma.

PMID- 20815275
TI  - [Mechanism of Chinese herbal compound Zilongjin for antagonizing multi-drug
      resistance of tumor cells].
AB  - OBJECTIVE: To explore the mechanism of action of Zilongjin (ZLJ) in antagonizing
      multi-drug resistance (MDR) of tumor cells. METHODS: MDR tumor cells, including
      human breast cancer cell line MCF-7 and MCF-7/DOX, and human oral epithelial
      cancer cells KB and KBV200, were treated with ZLJ. The inhibition of ZLJ on cell
      proliferation was determined with MTT assay; cell cycle and fluorescence dye
      Rhodamine 123 intensity were detected by flow cytometry; and the expression of
      related proteins was examined by Western blot. RESULTS: IC50 values in MDR cells
      after ZLJ treatment were similar to those in sensitive cells; MDR cells showed no
      cross resistance to ZLJ. Flow cytometric analysis showed that the cell cycles of
      either sensitive or MDR cells were arrested at S phase after exposure to ZLJ.
      Using ZLJ singly showed a weak inhibition on MDR of MCF-7/ DOX and KBV200 cells,
      but when used in combining with doxorubicin or vincistine, it evidently increased
      their cytotoxicity. Expression of P-glycoprotein in MCF-7/DOX cells decreased
      after ZLJ treatment in a time-dependent manner. Western blot showed that ZLJ
      could cause the apoptosis marker protein PARP cleavage to initiate the apoptotic
      pathway. CONCLUSIONS: The proliferation of tumor cells with MDR could be
      inhibited by ZLJ and they show no cross resistance to ZLJ. The inhibitory effect
      is related to the activation of apoptotic pathway and the decrease of P
      glycoprotein expression.

PMID- 20815276
TI  - [Apoptosis inducing effect of Hechanpian on human lung adenocarcinoma A549
      cells].
AB  - OBJECTIVE: To study the apoptosis inducing effects of Hechanpian (HCP) on human
      lung adenocarcinoma A549 cells. METHODS: HCP containing rat serum was prepared
      and applied on A549 cells. The cell growth inhibition rate was tested by MTT
      assay; the effect of HCP on cell apoptosis was observed with Propidium iodide
      (PI) staining and flow cytometry analysis; the mRNA expression of epidermal
      growth factor receptor (EGFR) was detected through RT-PCR. RESULTS: The growth of
      A549 cells was obviously inhibited after being treated by HCP containing serum,
      and the cells presented an apoptotic change. The cell apoptosis rate after
      treated by serum containing 10% and 20% HCP was 20.5% and 33.2%, respectively,
      significantly higher than that in the control (6.1% in cells didn't treated with
      HCP, P < 0.05). Compared with control, EGFR mRNA expression in HCP treated cells
      was significantly lower (P < 0.05). CONCLUSION: HCP has apoptosis inducing effect
      on A549 cell, and its molecular mechanism is probably correlated with the
      inhibition of EGFR gene transcription.

PMID- 20815277
TI  - [Effect of Bushen Yiqi Huoxue Recipe on placental trophoblast apoptosis in fetal
      growth restricted pregnant rat].
AB  - OBJECTIVE: To observe the effect of Bushen Yiqi Huoxue Recipe (BYHR, a Chinese
      medical prescription for reinforcing Shen, replenishing qi and promoting blood
      circulation) on placental trophoblast apoptosis in fetal growth restricted (FGR)
      pregnant rat for the sake of explore its mechanism of action in treating FGR.
      METHODS: FGR animal model was established by passive smoking, 32 pregnant rats
      were divided into four groups at random: the normal group, the model group, the
      Chinese medicine (CM) group (model rats treated by BYHR) and the Western medicine
      (WM) group (model rats treated by arginine). The histological change of placenta
      was examined with HE stain, the trophoblast apoptosis was detected by TUNEL and
      RT-PCR, and the expressions of Bcl-2 and Bax in the placenta were detected by
      immunohistochemical method. RESULTS: Blood stasis and villous ischemia were seen
      in placenta of FGR model rats. Placental microcirculation was significantly
      improved in the CM group, but in the WM group only partially improved. The median
      apoptotic index of syncytial trophoblast cells in the four groups, in normal,
      model, CM, and WM order, was 45%, 75%, 57% and 70%, as compared with the model
      group, it was much lower in the normal group and the CM group (P < 0.01), but a
      similar level was shown in the WM group. No significant difference in mRNA and
      protein expressions of Bcl-2 and Bax was found among the four groups. CONCLUSION:
      BYHR can improve the placental microcirculation in FGR rats to prevent excessive
      apoptosis through a mechanism other than the classical Bax/Bcl-2 apoptotic
      pathway, which needs further exploring.

PMID- 20815278
TI  - [Study on the mechanism of action of total flavonoids of Litsea coreana for
      reducing blood glucose level in rat with type 2 diabetes mellitus].
AB  - OBJECTIVE: To explore the possible mechanism of total flavonoids of Litsea
      coreana (TFLC) on reducing blood glucose level in rat with type 2 diabetes
      mellitus (T2DM). METHODS: Male SD rats of T2DM allocated in two groups were
      treated with 400 mg/kg TFLC or metformin respectively via gastrogavage for 6
      weeks. Blood routine biochemical indices in rats were measured; pathology of
      rats' liver was examined with HE stain under transmission electron microscopy;
      levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in liver
      homogenate were determined, and the expression of protein tyrosine phosphatase 1B
      (PTP1B) in liver was detected using RT-PCR at the terminal of the experiment.
      RESULTS: Biochemical measuring showed that the glucose tolerance of rats after
      treatment was markedly improved in both groups. Meantime, levels of fast blood
      glucose (FBG), glycohemoglobin (HbA1c), fast blood insulin (FINS), free fatty
      acid (FFA), total cholesterol (TC), triglyceride (TG) and low density lipoprotein
      cholesterol (LDL-C), as well as MDA level in liver were decreased, while levels
      of high density lipoprotein-cholesterol (HDL-C) in blood and SOD in liver were
      significantly increased in both groups after treatment, showing insignificant
      difference between two treatment groups. Light microscopic examination showed
      markedly fatty degeneration of liver, and electron microscopic examination found
      mitochondria swelling and endoplasmic reticulum breakage in liver of T2DM rats,
      but these changes were ameliorated to some extent after treatment. The elevated
      PTP1B expression in liver of T2DM rats was decreased in the TFLC treated group,
      but unchanged in the metformin treated group. CONCLUSION: TFLC can significantly
      decrease the blood levels of glucose and lipid and ameliorate oxidation stress in
      liver; its mechanism of action in improving insulin resistance might be related
      with its suppression on PTP1B expression in rat's liver to enhance the insulin
      signaling pathway.

PMID- 20815279
TI  - [Effects of different assemblages with components of Shengmai Powder on
      glucocorticoid receptor in liver of thermal injured rat].
AB  - OBJECTIVE: To study the effects of different assemblages formed by components of
      Shengmai Powder (SMP) on glucocorticoid receptor (GR) in liver of thermal injured
      rat to find the optimal ratio of assembling for GR regulation. METHODS: With a
      orthogonal design adopted, the dosage of each component of SMP, including the
      total saponins of Ginseng (G), the water extract of lilyturf root (L), and the
      water extract of schisandra fruit (S), was ranked in three levels, namely, no
      participating, low dosage (G 7.1 mg, L 17.2 mg, S 9.6 mg), high dosage (G 14.2
      mg, L 34.4 mg, S 19.2 mg). The components were assigned by L9(3(4)) orthogonal
      table and grouped, the best assembling ratio was determined through direct and
      variance analysis. RESULTS: After being acted by the different assemblages, the
      maximum binding volume of GR in rat's liver cell suspension was 161 +/- 26
      fmol/mg protein in group 1, 271 +/- 40 fmol/mg protein in group 2, 166 66 fmol/mg
      protein in group 3, 222 +/- 45 fmol/mg protein in group 4, 192 +/- 26 fmol/mg
      protein in group 5, 194 +/- 23 fmol/mg protein in group 6, 166 +/- 15 fmol/mg
      protein in group 7, 165 +/- 47 fmol/mg protein in group 8 and 211 +/- 79 fmol/mg
      protein in group 9. The optimal GR level appeared during the dosage of G, L and S
      was 7.1 mg, 17.2 mg and 19.2 mg, respectively. CONCLUSION: The best assembling
      ratio of SMP for regulating GR in the liver of thermal injured rat was G:L:S =
      3:3:4.

PMID- 20815280
TI  - [Protective effect of musk extract on rat's cerebral cortical neurons with
      inflammatory injury].
AB  - OBJECTIVE: To investigate the protective effects of musk extract (ME) and its
      possible mechanism on rat's cerebral cortical neurons with inflammatory injury
      induced by lipopolysaccharide (LPS). METHODS: Neurons and astrocytes from newborn
      rat cerebral cortex were cultured in vitro respectively, and the astrocyte
      conditioned medium (ACM), obtained by treating astrocytes with 10 mg/L LPS and
      different concentrations of ME for 24 h, was added in the culture fluid of
      neurons. The survival rate and apoptotic rate of neurons were measured by MTT
      method and AO/EB stain; and the changes of inflammatory factors in the ACM were
      determined by ELISA. RESULTS: The survival rate (%) of neurons treated by ACM
      with ME in concentrations of 18 mg/L, 36 mg/L, 72 mg/L and 144 mg/L was 52.55 +/-
      3.52, 55.77 +/- 2.36, 64.89 +/- 3.45 and 73.67 +/- 1.80, respectively,
      significantly higher than that in the model neurons (43.62 +/- 4. 51, P < 0.05),
      while the apoptotic rate (%) in them, 68.11 +/- 2.16, 44.27 +/- 3.68, 32.56 +/-
      2.14 and 21.89 +/- 2.46, respectively, was significantly lower than that in model
      neurons (71.33 +/- 3.25, P < 0.05 or P < 0.01). Level of IL-6 was decreasing
      along with the raising of ME concentration in the ACM, showing a concentration
      dependent state. CONCLUSION: ME shows apparent protective effect on neurons
      against inflammatory injury, especially in a high concentration (144 mg/L), which
      may be associated with the reduction of IL-6 secreted by astrocytes.

PMID- 20815281
TI  - [Effect of depside salt from salvia miltiorrhizae in repairing advanced glycation
      end products-induced late endothelial progenitor cell dysfunction and its
      molecular mechanism].
AB  - OBJECTIVE: To investigate the effects of depside salt from salvia miltiorrhizae
      (DSSM) in repairing advanced glycation end products (AGE)-induced late
      endothelial progenitor cell (EPC) dysfunction, and its possible molecular
      mechanism. METHODS: Mononuclear cells (MNCs) were separated using density
      gradient centrifugation from human umbilical cord blood, and cultured with EGM-2
      MV culture fluid to late EPCs. Then the EPCs were divided into 5 groups: Group A
      incubated with 200 microg/mL AGE-modified bovine serum albumin (AGE-albumin)
      alone (A), Groups B, C and D with equal dosage of AGE-albumin plus DSSM at
      different dosages (0.1 microg/mL, 1 microg/mL, and 10 microg/mL), Group E with
      200 microg/mL of unmodified-AGE. The late EPCs apoptosis was detected by Annexin
      V+/PI double-stain, angiogenic capacity was detected by ECMatrix-gel, mRNA
      expressions of the receptor for AGE (RAGE) and endothelial nitric oxide synthase
      (eNOS) were measured by reverse-transcriptase polymerase chain reaction (RT-PCR),
      and the protein expressions of RAGE, eNOS and protein kinase (Akt) were measured
      by Western blot. RESULTS: Compared with Group E, in Group A, the Annexin V+/PI-
      ratio and expression of RAGE in EPCs increased, the angiogenic capacity, mRNA and
      protein expressions of eNOS, and protein expression of Akt decreased
      significantly. These abnormal changes in Groups C and D were significantly
      smaller than those in Group A (P < 0.05 or P < 0.01). And all the indices in
      Group D were adjacent to those in Group E, showing insignificant difference
      between the two groups (P > 0.05). CONCLUSIONS: AGE could injure the function of
      EPCs, revealing increase of cell apoptosis and migration, deprivation of
      angiogenic capacity in vitro. DSSM could repair the EPCs dysfunction induced by
      AGE-albumin. Up-regulation of eNOS and Akt in these cells may be involved in the
      mechanism.

PMID- 20815282
TI  - [Effects of control-releasing arsenic trioxide-eluting stent on intimal smooth
      muscle cells and type III collagen in canine coronary artery post-stent model].
AB  - OBJECTIVE: To study the safety and efficacy of control-releasing arsenic trioxide
      (As2O3)-eluting stent on intimal smooth muscle cells (SMC) and type III collagen
      (CIII) in canine coronary artery post-stent model. METHODS: Twenty-four
      experimental canines were equally divided into 4 groups, the three tested groups
      were deployed by stents with different dosage of As2O3 (1.6 microg/mm2, 2.4
      microg/mm2 and 3.2 microg/mm2 in low, median and high dose groups, respectively)
      and coated with polybutyl methacrylate/nano silica and poly-lactide-coglycolide
      in mild oversizing (stent/vessel ratio of 1.3:1) in left anterior descending
      (LAD) or circumflex coronary arteries (LCX), while the control group only by
      simple coated stent without As2O3. The effect was assessed 4 weeks after stent
      implantation in terms of vascular histomorphology, and changes of SMC and C III
      expressions were detected using immunohistochemical analysis. RESULTS: Subintimal
      hemorrhage, medial/adventitial necrosis, thrombosis and inflammatory cell
      infiltration were not found and integral endothelium could be seen under
      screening electron microscopy in all groups. Positive expression of SMC and CIII
      in the tested groups, especial in the high dose As2O3 group, was more weaker than
      that in control group. Histo-morphological analysis showed that the neo-genetic
      intimal area and vascular stenosis were lower, but the mean luminal diameter was
      larger in the three tested groups than that in the control group (P < 0.01).
      Comparisons of various indices between tested groups treated by different doses
      of As2O3 showed that the difference between high/median dose vs. low dose was
      significant (P < 0.01), but that between high dose vs. median dose was
      insignificant (P > 0.05). CONCLUSION: Control-releasing As2O3-eluting stent shows
      a reliable and safe effect in preventing and treating post-stent restenosis by
      its dose-dependent inhibition on expressions of SMC and CIII to suppress the neo
      genesis of intimal hyperplasia.

PMID- 20815283
TI  - [Effect of Shenqi compound on PTEN/PI3K signal transduction in GK rats with
      diabetes mellitus macroangiopathy].
AB  - OBJECTIVE: To research the effects and mechanism of Shenqi compound (SQC) on
      PTEN/ PI3K signal transducing path and angiogenesis in Goto-Kakizaki (GK) rats
      with diabetes mellitus type 2 (DM2) caused macroangiopathy. METHOD: GK rats with
      blood sugar > or = 11.1 mmol/L were divided into 4 groups, the GK group, the
      model group, the Western medicine (WM) group treated by atorvastatin 1.5 mg/(kg x
      d) and the Chinese medicine (CM) group treated with SQC 1.44 g/(kg x d). All were
      fed 35 days with high fatty diet, but to the latter three groups, N omega-nitriyl
      L-arginine methyl ester 0.1 mg/mL was added into their drinking water for
      macroangiopathy model establishing. Besides, a group of normal Wistar rats fed
      with ordinary forage was set for control. Rat's blood glucose and lipids were
      measured, morphology of abdominal aorta wall tissue was observed with HE
      staining, and mRNA expressions of PTEN and PI3Kp85 in aortic wall were detected
      by Real-time PCR. RESULTS: General condition, gluco-lipid metabolism and aortic
      morphology in the CM group were significantly better than those in the model
      group. PTEN mRNA expression in the CM group (1.10 +/- 0.48) was significantly
      higher than that in the GK group (0.63 +/- 0.16) and the model group (0.17 +/-
      0.07, both P < 0.01), but near to that in the WM group (1.11 +/- 0.46), while the
      PI3Kp85 mRNA expression in the TCM group (0.19 +/- 0.05) was lower than that in
      the GK group (1.38 +/- 0.43, P < 0.01), but near to that in the model group (0.33
      +/- 0.09) and the WM group (0.11 +/- 0.06, both P > 0.05). CONCLUSION: SQC could
      increase the PTEN mRNA expression and restrain the PI3Kp85 mRNA expression in
      aorta, which is possibly the partial mechanisms of action of the remedy in
      inhibiting angiogenesis and preventing diabetic macroangiopathy.

PMID- 20815284
TI  - [Progress of research on aspirin resistance and its related course of integrative
      medical research].
AB  - Aspirin is the most classic anti-platelet drug, plays its important role in
      preventing and treating cardio- and cerebro-vascular diseases for its excellent
      potency ratio; however, there exists individual difference in its anti-platelet
      effect, aspirin resistance (AR) presented in about 25%-40% of patients, which
      seriously influences the intervention effect of aspirin. So AR has become a
      clinical problem that attached more attention. In this paper, the authors put
      forward a new thinking for clinical studying and inventing new effective Chinese
      drugs on AR by means of screen out AR suffered from cardio/cerebro-vascular
      patients long-term received aspirin; find their gene difference sites from MtSNP
      to establish a foundation for AR predication and reasonable strategy formation;
      meantime, through platelet intervention in vitro adopting uniform design
      optimization method to explore the best compatibility and matching relationship
      of anti-platelet Chinese medicine for AR prevention and treatment, so as to fully
      display the multi-target intervening effects of Chinese drug-therapy.

PMID- 20815285
TI  - [Significance of anti-inflammation and immune regulation in the treatment of
      diabetic nephropathy].
AB  - The pathogenesis of diabetic nephropathy is influenced by multiple factors, among
      them, the pivotal action of inflammation on the development process of diabetic
      nephropathy has been proven with more and more evidences. In this article, the
      role of inflammation in the pathogenesis of diabetic nephropathy, the progress on
      researches of anti-inflammation and immune regulation, as well as the Chinese
      medicine therapy against diabetic nephropathy are introduced.

PMID- 20815286
TI  - [English translation of Chinese medicine on the translation of Xu and Shi in
      Chinese medicine].

PMID- 20815287
TI  - [English translation of Chinese medicine term "Shenming"].

PMID- 20815288
TI  - [Toll-like receptor and its pathway: a possible effect target of immune
      reconstitution in HIV/AIDS patients treated by Chinese medicine].

PMID- 20815289
TI  - [Progress of integrative medical treatment of recurrent natural abortion induced
      by immune factor].

PMID- 20815290
TI  - Depression and emotional disorders in patients with physical illnesses:
      scientific knowledge and interventions that innovate practice.

PMID- 20815291
TI  - Psychological and biological mechanisms of cytokine induced depression.
AB  - Depression is frequently seen in patients with medical illnesses yet the link
      between medical illnesses and depression remains unclear. There is increasing
      data to suggest that the array of depressive symptoms experienced by the
      medically-ill may involve inflammation. The activation of the immune system and
      the subsequent release of innate immune products such as cytokines can have
      important effects on behaviour. The treatment of choice for chronic viral
      hepatitis C, interferon-alpha IFN-alpha, acutely induces the production and
      release of other innate immune cytokines, and has been indicated to cause
      clinically significant depression in 30% of patients receiving treatment. This in
      turn can impair quality of life and affect treatment compliance. We and others
      use IFN-alpha induced depression as a model to identify alterations in
      psychological and biological pathways that predispose to depression in the
      medically-ill, and thus provide an explanatory link between inflammation and the
      subsequent behavioural changes. In this editorial, we aim to describe the main
      biological pathways involved in IFN-induced depression and to discuss
      psychological, clinical and biological factors that have been found to predict
      those who will develop more severe psychiatric symptoms during treatment with IFN
      alpha. Among these, particular attention would be given to psychological traits,
      genetic polymorphisms regulating inflammation and serotonergic function, and
      changes in plasma levels of pro-inflammatory cytokines.

PMID- 20815292
TI  - Diagnosis and treatment of depression in patients with advanced illness.
AB  - This article reviews common sources of suffering in patients with advanced
      illness, identifies challenges in appropriately diagnosing and treating
      depression in this setting, and examines the relationship between depression and
      other key clinical outcomes in the setting of advanced disease. A systematic
      literature review was conducted. Most of the existing research on patients with
      advanced illness has been conducted with cancer patients. Approximately 18
      percent of patients with advanced illness meet criteria for major or minor
      depression; multiple psychiatric co-morbidities occur frequently. Prevalence
      rates increase as patients become sicker. However, depression is frequently
      underdiagnosed and undertreated in the setting of advanced illness. One of the
      key clinical challenges is differentiating depression from grief. Both
      psychosocial and psychopharmacologic interventions have been shown to be
      effective in treating depression in patients with advanced cancer. In conclusion,
      depression is a regular complication of advanced illness, reduces quality of
      life, compromises family member function, interferes with treatment decisions,
      and may shorten survival. However, numerous effective treatment approaches,
      including both medications and psychotherapy, exist and can be used to alleviate
      depression.

PMID- 20815293
TI  - Depression and treatment nonadherence in type 2 diabetes: assessment issues and
      an integrative treatment approach.
AB  - Research has found that depression is more common among individuals with diabetes
      and is associated with worse diabetes outcomes including treatment nonadherence,
      worse glycemic control, higher risk of diabetes complications, greater functional
      impairment, and increased risk of mortality. These patterns of association have
      led to an increase in research investigating the relationship between diabetes
      and depression. There remain important questions about the relationship between
      depression and diabetes and an unmet need for treatment approaches that are
      successful in ameliorating depression and improving diabetes outcomes. The
      current commentary discusses several conceptual issues related to the measurement
      of depression in diabetes, argues for the importance of health behavior and
      treatment adherence in approaching the problem of depression in diabetes, and
      provides an example of a treatment approach that incorporates the treatment of
      depression with strategies aimed at improving treatment adherence in order to
      maximize effects on diabetes outcomes.

PMID- 20815294
TI  - What is a clinical trial protocol?
AB  - Trial protocols are documents that describe the objectives, design, methodology,
      statistical considerations and aspects related to the organization of clinical
      trials. Trial protocols provide the background and rationale for conducting a
      study, highlighting specific research questions that are addressed, and taking
      into consideration ethical issues. Trial protocols must meet a standard that
      adheres to the principles of Good Clinical Practice, and are used to obtain
      ethics approval by local Ethics Committees or Institutional Review Boards.

PMID- 20815295
TI  - The potential role of the parietal lobe in schizophrenia.
AB  - Although the anatomy of the parietal lobe has been under-investigated in
      schizophrenia, some magnetic resonance imaging studies have shown decreased
      volumes, suggesting its possible implication for the pathophysiology of the
      disease.

PMID- 20815296
TI  - Mechanisms of impulsivity in bipolar disorder and related illness.
AB  - AIMS: Impulsivity is a multifaceted aspect of behavior that is prominent in
      psychiatric disorders and has serious behavioral consequences. This paper reviews
      studies integrating behavioral and physiological mechanisms in impulsivity and
      their role in severity and course of bipolar and related disorders. METHODS: This
      is a review of work that used questionnaire, human behavioral laboratory, and
      neurophysiological measurements of impulsivity or related aspects of behavior.
      Subjects included individuals with bipolar disorder, substance-use disorders,
      antisocial personality disorder, and healthy controls. RESULTS: Models of
      impulsivity include rapid-response impulsivity, with inability to reflect or to
      evaluate a stimulus adequately before responding, and reward-based impulsivity,
      with inability to delay response for a reward. In normal subjects, rapid-response
      impulsivity is increased by yohimbine, which increases norepinephrine release.
      Impulsivity is increased in bipolar disorder, whether measured by questionnaire,
      by measures of rapid-response impulsivity, or by measures of ability to delay
      reward. While affective state has differential effects on impulsivity,
      impulsivity is increased in bipolar disorder regardless of affective state or
      treatment. Impulsivity, especially rapid-response, is more severe with a highly
      recurrent course of illness or with comorbid substance-use disorder, and with
      history of medically severe suicide attempt. In antisocial personality disorder,
      rapid-response impulsivity is increased, but reward-based impulsivity is not. In
      general, impulsivity is increased more in bipolar disorder than in antisocial
      personality disorder. In combined bipolar disorder and antisocial personality
      disorder, increased impulsivity is associated with substance-use disorders and
      suicide attempts. CONCLUSIONS: Impulsivity is associated with severe behavioral
      complications of bipolar disorder, antisocial personality disorder, and substance
      use disorders.

PMID- 20815297
TI  - The economic impact of initiatives to reduce stigma: demonstration of a modelling
      approach.
AB  - AIMS: This paper seeks to provide a methodology to assess the cost-effectiveness
      of anti-stigma campaigns for people with mental health problems. METHODS: The
      costs of running a national campaign in Scotland were obtained and combined with
      the number of adults in the Scottish population and the estimated number of
      people with improved attitudes towards people with mental health problems. A
      decision model was constructed to estimate the economic impact of a campaign in
      terms of increased use of services by people with depression and increased work
      time. RESULTS: If the campaign caused 10% of changed attitudes then it was
      estimated to cost pound 35 per one less person who felt that people with mental
      health problems were dangerous and pound 186 per one less person who felt the
      public needs protection from people with mental health problems. The decision
      model suggested extra economic benefits (employment gains minus service costs) as
      a result of an anti-stigma campaign compared to the absence of a campaign.
      CONCLUSIONS: Data on the economic impact of anti-stigma campaigns are scarce and
      evaluation is intrinsically difficult. We have demonstrated a method to conduct
      such analyses. The model proposed here should be tested further as data become
      available.

PMID- 20815298
TI  - Service user perspectives on the impact of a mental illness diagnosis.
AB  - AIM: To provide a conceptual and practical analysis of the impacts of mental
      health diagnoses on consumers and to consider how service users might contribute
      to the new psychiatric classifications currently being drawn up. METHODS: A
      search was carried out revealing a very sparse literature on this topic.
      Consultations with service users were conducted and the views of experts sought.
      RESULTS: Diagnosis is important as it marks the formal status of psychiatric
      patient being conferred. Consumers react differently, and often, negatively to
      this. Stigma can follow from a diagnosis. The process of giving a diagnosis can
      range from one of negotiation and taking the person's strengths into account to
      the blunt allocation of an unwanted label. Consumers can be reduced to their
      diagnosis so it becomes their whole personhood and this can have an effect on
      their sense of self. However, consumers are not passive victims and have their
      own strategies for dealing with these issues. CONCLUSION: Consumers can use these
      experiences to make contributions to the new diagnostic classification systems
      and to future research.

PMID- 20815299
TI  - Delinquency in context; neighbourhood and gender interactions among adolescents.
AB  - AIM: Delinquency among adolescents and antecedent conduct disorder among children
      has been recognized as a growing public mental health problem in contemporary
      societies. The contribution of the neighbourhood environment to delinquent
      behaviour was examined in a cohort of Dutch adolescents (aged approximately 11
      years at baseline; n = 394). METHODS: Multilevel regression analyses estimated
      associations between baseline neighbourhood socioeconomic status and social
      capital, and delinquent behaviour two years later controlling for individual
      level variables. RESULTS: A significant interaction effect was found between
      neighbourhood environment variables and gender in models of delinquency,
      indicating that associations between neighbourhood environment variables and
      delinquency were apparent, for the most part, in girls only. However, higher
      level of neighbourhood informal social control was associated with increased
      delinquency rates in boys. CONCLUSION: In girls there is a longitudinal
      association between neighbourhood characteristics and delinquency, suggesting
      complex gender differences in the way the wider social environment impacts on
      behavioural outcomes.

PMID- 20815300
TI  - The need for closure in caregivers of people with psychosis.
AB  - AIM: The aim of the study was to determine how carer need for closure relates to
      expressed emotion. It also examined the links between carer need for closure and
      patient functioning including patient need for closure. METHODS: In a cross
      sectional study, 70 caregivers of patients with psychosis completed the Need for
      Closure Scale (NFCS), the Camberwell Family Interview (CFI) and measures of
      distress, burden, coping and social network. The NFCS was assessed in terms of
      its two primary dimensions: a need for simple structure (NFSS) and Decisiveness.
      Patients also completed measures of psychotic symptoms and affect, and in 50
      matched caregiver patient dyads, direct comparisons were undertaken between
      caregiver and patient NFCS scores. RESULTS: No links were found between caregiver
      NFC and EE in this predominately low EE sample. More decisive carers had higher
      levels of self esteem, were less distressed, and resorted less to avoidant
      coping. The need for simple structure was greater in carers who lacked a
      confidante. As predicted, patients reported significantly higher NFSS and lower
      Decisiveness scores than carers, but no relationship was observed between
      caregiver NFC and patient symptoms of psychosis. CONCLUSIONS: Carers reporting
      confident decision making were also more likely to report adaptive functioning in
      terms of having lower levels of avoidant coping and distress, and higher levels
      of self esteem. The results suggest that this style of thinking might be a
      helpful way of coping with some of the difficulties involved in caring for
      someone with psychosis. D

PMID- 20815301
TI  - A predictive model to allocate frequent service users of community-based mental
      health services to different packages of care.
AB  - AIM: To develop predictive models to allocate patients into frequent and low
      service users groups within the Italian Community-based Mental Health Services
      (CMHSs). To allocate frequent users to different packages of care, identifying
      the costs of these packages. METHODS: Socio-demographic and clinical data and GAF
      scores at baseline were collected for 1250 users attending five CMHSs. All
      psychiatric contacts made by these patients during six months were recorded. A
      logistic regression identified frequent service users predictive variables.
      Multinomial logistic regression identified variables able to predict the most
      appropriate package of care. A cost function was utilised to estimate costs.
      RESULTS: Frequent service users were 49%, using nearly 90% of all contacts. The
      model classified correctly 80% of users in the frequent and low users groups.
      Three packages of care were identified: Basic Community Treatment (4,133 Euro per
      six months); Intensive Community Treatment (6,180 Euro) and Rehabilitative
      Community Treatment (11,984 Euro) for 83%, 6% and 11% of frequent service users
      respectively. The model was found to be accurate for 85% of users. CONCLUSION: It
      is possible to develop predictive models to identify frequent service users and
      to assign them to pre-defined packages of care, and to use these models to inform
      the funding of psychiatric care.

PMID- 20815302
TI  - Development and validation of a Stress-related Vulnerability Scale.

PMID- 20815303
TI  - [Family members' assessment of community mental health services: a survey in four
      Italian regions].

PMID- 20815304
TI  - Sublingual immunotherapy in polysensitized patients: effect on quality of life.
AB  - BACKGROUND: Quality of life (QOL) is an important issue in allergic rhinitis and
      has been evaluated in a number of studies that have shown how it is impaired in
      untreated patients and improved by effective treatment. However, there are no
      data concerning QOL after sublingual immunotherapy (SLIT) in polysensitized
      patients. OBJECTIVE: To evaluate the effect, in real-life clinical practice, of
      SLIT on QOL in a population of polysensitized patients with allergic rhinitis.
      METHODS: We prospectively evaluated 167 consecutively enrolled polysensitized
      patients with allergic rhinitis. QOL was measured in all cases with the
      Rhinoconjunctivitis Quality of Life Questionnaire at baseline and after 1 year of
      SLIT (performed in approximately 70% of cases using single allergen extracts
      provided by the same manufacturer). RESULTS: The most frequent causes of
      sensitization were grass pollen, Parietaria, and house dust mites. The mean
      number of sensitizations per patient was 3.65. SLIT was performed with 1 extract
      in 123 patients (73.6%), with 2 extracts in 31 patients (18.6%), and with more
      than 2 extracts in 13 patients (7.8%). The mean values of all the QOL items
      improved significantly (P < .01 in all cases), with the following reductions
      noted: activities, 3.96 to 2.89; sleep, 2.07 to 1.56; general problems, 2.16 to
      1.5; practical problems, 3.69 to 2.58; nasal symptoms, 3.57 to 2.50; eye
      symptoms, 2.92 to 1.83; and emotional aspects, 2.2 to 1.44. CONCLUSIONS: This
      study provides evidence that QOL can be improved in polysensitized patients
      treated with SLIT, and that the use of just 1 or 2 allergen extracts seems to be
      sufficient and effective in terms of improving QOL.

PMID- 20815305
TI  - Extent and burden of allergic diseases in elementary schoolchildren: a national
      multicenter study.
AB  - BACKGROUND: Scarcity of standardized, comparable data on allergic diseases in
      schoolchildren in Turkey requires further multicenter studies based on the use of
      objective tools in addition to parent-completed questionnaires to improve the
      validity and reliability of results. METHODS: Using International Study of Asthma
      and Allergies in Children (ISAAC) Phase II tools, elementary schoolchildren aged
      9 to 11 years were surveyed in 5 city centers in different regions of Turkey.
      RESULTS: We surveyed 6963 children from 70 schools and found that 35% had had at
      least 1 symptom of allergic diseases in the past year. Based on parental reports,
      the overall prevalence rates for wheezing, rhinoconjunctivitis, and eczema in the
      past year were 15.8%, 23.5%, and 8.1%, respectively. The overall frequencies of
      atopy, flexural dermatitis, and bronchial hyperreactivity were 18.9%, 3.6%, and
      24.2%, respectively. There were large variations in the prevalence of both
      symptoms and objective signs between study centers. Absence from school for at
      least 1 day was reported for 34.2% of children with a diagnosis of asthma or
      allergic rhinitis. CONCLUSIONS: Approximately one third of elementary
      schoolchildren reported symptoms compatible with allergic diseases in the past
      year. The interregional differences in both symptoms and objective test results
      are possibly due to differences in environmental conditions. Unfortunately,
      serious problems are still encountered in the timely and proper diagnosis and
      treatment of allergic diseases.

PMID- 20815306
TI  - Peanut allergy: is maternal transmission of antigens during pregnancy and
      breastfeeding a risk factor?
AB  - BACKGROUND: Peanut allergy is an important public health problem in western
      countries. However, the risk factors associated with this allergy remain
      uncertain. OBJECTIVE: To determine whether the consumption of peanuts during
      pregnancy and breastfeeding is a risk factor for peanut allergy in infants.
      METHODS: We enrolled 403 infants in a case-control study. The cases were infants
      aged 18 months or less with a diagnosis of peanut allergy based on a history of
      clinical reaction after exposure to peanuts and the presence of peanut-specific
      immunoglobulin E. Controls were age-matched infants with no known clinical
      history or signs of atopic disease. The mothers of the children filled out a
      detailed questionnaire about maternal diet during pregnancy and breastfeeding,
      the infant's diet, the presence of peanut products in the infant's environment,
      and family history of atopy. RESULTS: The mean (SD) age of cases was 1.23 (0.03)
      years. The groups were comparable in terms of the rate and duration of
      breastfeeding. However, the reported consumption of peanuts during pregnancy and
      breastfeeding was higher in the case group and associated with an increased risk
      of peanut allergy in offspring (odds ratio [OR], 4.22 [95% confidence interval
      [CI], 1.57-11.30 and OR, 2.28 [95% CI, 1.31-3.97] for pregnancy and
      breastfeeding, respectively). Overall, the infants with peanut allergy did not
      seem to be more exposed to peanut products in their environment than the
      controls. CONCLUSION: Early exposure to peanut allergens, whether in utero or
      through human breast milk, seems to increase the risk of developing peanut
      allergy.

PMID- 20815308
TI  - Clinical correlates and determinants of airway inflammation in pediatric asthma.
AB  - BACKGROUND: Airway inflammation is a key component in the pathophysiology of
      asthma. However, neither its role in the clinical features of asthma nor the
      factors affecting the degree of inflammation have been fully defined. METHODS: We
      determined the fractional exhaled nitric oxide concentration (FE(NO)) using a
      portable device (NIOX-MINO, Aerocrine, Solna, Sweden) in a consecutive sample of
      149 asthmatic children aged 6 to 14 years. In order to establish an association
      with FE(NO), we analyzed symptoms, spirometric parameters before and after a
      bronchodilator test, and the impact of asthma on quality of life during the
      previous 4 weeks. We also investigated how clinical variables that regulate
      inflammation affected FE(NO). RESULTS: In patients not treated with inhaled
      corticosteroids (ICs), FE(NO) was higher when specific symptoms (wheeze and
      cough) had been present during the previous 4 weeks; however, we were unable to
      establish a relationship with symptom frequency, bronchodilator use, asthma
      crises, hospital admissions, limitation of daily activities, or spirometry
      results. In patients treated with ICs, FE(NO) was not related to the clinical
      expression of asthma, except for a reduced ratio of forced expiratory volume in 1
      second to forced vital capacity, both before and after bronchodilation. The main
      determinant of FE level in untreated patients was sensitization to house dust
      mite. In patients treated with ICs, FE(NO) was only associated with adherence to
      therapy. CONCLUSION: Airway inflammation, as determined by FE(NO), is only weakly
      associated with the clinical expression of asthma and spirometry results.
      Adherence to treatment is the main determinant of the degree of inflammation in
      patients taking ICs.

PMID- 20815307
TI  - Grass pollen, aeroallergens, and clinical symptoms in Ciudad Real, Spain.
AB  - BACKGROUND: In allergic individuals, onset of symptoms is related to atmospheric
      pollen grain counts and aeroallergen concentrations. However, this relationship
      is not always clear. OBJECTIVES: To analyze the correlation between grass pollen
      grain and aeroallergen concentrations in Ciudad Real, Spain, during the year 2004
      and establish their association with symptoms in patients with allergic asthma,
      rhinitis, or both. METHODS: Two different samplers were used to assess allergen
      exposure: a Burkard spore trap to collect pollen grains and a high-volume air
      sampler to collect airborne particles. Individual filters were extracted daily in
      phosphate-buffered serum and analyzed by enzyme-linked immunosorbent assay based
      on serum containing high titers of specific immunoglobulin (Ig) E to grasses. The
      study population comprised 27 grass-allergic patients whose symptoms and
      medication were recorded daily. RESULTS: Grass pollens were detected between
      April 28 and July 18. There was a positive correlation between pollen grain
      counts and symptoms (r = 0.62; P > .001). Grass aeroallergens were detected not
      only during the grass pollination period, but also before and after this period.
      There was also a very significant correlation between aeroallergen levels and
      symptoms (r = 0.76; P < .0001). The threshold level for grass pollen was 35
      grains/m3. CONCLUSIONS: Grass-related allergenic activity is present throughout
      the year, demonstrating the existence of aeroallergens outside the pollen season.
      Symptoms in allergic patients may be related to airborne particle concentrations.
      This fact should be taken into account in the clinical follow-up and management
      of allergic patients.

PMID- 20815310
TI  - Effects of cigarette smoke extract and nicotine on bronchial tone and
      acetylcholine-induced airway contraction in mouse lung slices.
AB  - BACKGROUND: Tobacco smoke is a key risk factor for chronic obstructive pulmonary
      disease, but it may also alter the pathophysiology of asthma. In the present
      study, we analyzed whether tobacco smoke has acute or chronic effects on
      bronchial tone and whether it alters bronchial reactivity in vitro. METHODS:
      Airways in murine lung slices were digitally recorded and the change in cross
      sectional area with time was quantified. T-bet KO mice served as a model for
      bronchial hyperreactivity. T-bet KO mice show a shift towards type 2 helper T
      lymphocytes and display histological as well as functional characteristics of
      asthma. Cigarette smoke extract (CSE) was obtained using commercially available
      cigarettes (Gauloise Blondes) by drawing cigarette smoke slowly through a water
      pump into a tube containing 10 mL of DMEM culture medium. RESULTS: Acute exposure
      to CSE led to relaxation of the airway. Acute exposure to nicotine resulted in a
      minor relaxation of the airway in Balb/C mice and in nonsignificant relaxation of
      the airway in T-bet KO mice. The nicotinic acetylcholine-receptor hexamethonium
      partially inhibited CSE-induced airway relaxation. Airway contraction in response
      to acetylcholine was stronger in T-bet KO mice than in Balb/C mice. After
      exposure to CSE or nicotine for 48 hours, acetylcholine-induced airway
      contraction was no longer different between the 2 types of mice. CONCLUSIONS: Our
      data indicate that acute exposure to CSE leads to airway relaxation, which is
      partially mediated by nicotine. Chronic exposure to CSE reverses bronchial
      hyperreactivity in the airways of T-bet KO mice; this effect can be mimicked by
      chronic exposure to nicotine.

PMID- 20815309
TI  - Prevalence of symptoms of eczema in Latin America: results of the International
      Study of Asthma and Allergies in Childhood (ISAAC) Phase 3.
AB  - BACKGROUND: The aim of the International Study of Asthma and Allergies in
      Childhood (ISAAC) was to evaluate the prevalence of symptoms of eczema among
      children living in different parts of Latin America. Data were from centers that
      participated in ISAAC Phase 3. METHODS: This was a cross-sectional questionnaire
      survey of 93,851 schoolchildren (6 to 7 years old) from 35 centers in 14 Latin
      American countries and 165,917 adolescents (13 to 14 years old) from 56 centers
      in 17 Latin American countries. RESULTS: The mean prevalence of current flexural
      eczema in schoolchildren was 11.3%, ranging from 3.2% in Ciudad Victoria (Mexico)
      to 25.0% in Barranquilla (Colombia). For adolescents, the prevalence varied from
      3.4% in Santo Andre (Brazil) to 30.2% in Barranquilla (mean prevalence, 10.6%).
      The mean prevalence of current symptoms of severe eczema among schoolchildren was
      1.5%, ranging from 0.3% in Ciudad Victoria, Toluca, and Cuernavaca (Mexico) to
      4.9% in La Habana (Cuba). For adolescents, the mean prevalence was 1.4%, ranging
      from 0.1% in Mexicali Valley (Mexico) to 4.2% in Santa Cruz (Bolivia). These
      prevalence values are among the highest observed during ISAAC Phase 3. In
      general, the prevalence of current symptoms of eczema was higher among the
      Spanish-speaking centers for both schoolchildren and adolescents. CONCLUSION:
      Environmental risk factors must be evaluated in order to identify potential
      causes for the differences observed, even in centers from the same country.

PMID- 20815311
TI  - Identification of clinically relevant cross-sensitization between Soliadgo
      virgaurea (goldenrod) and Hevea brasiliensis (natural rubber latex).
AB  - BACKGROUND: Solidago virgaurea (goldenrod) is a perennial weed from which no
      allergens have been identified. A high latex content in its leaves has been
      reported. Although not an airborne allergen, it may be an important occupational
      sensitizer. OBJECTIVE: To identify allergenic proteins in goldenrod and to
      determine whether they cross-react with Hevea brasiliensis latex. METHODS:
      Potential cross-reactive allergens in latex and goldenrod were investigated by
      immunoblot inhibition and ImmunoCAP inhibition analyses using serum from patients
      with clinically evident goldenrod and/or latex allergy. Cross reactivity between
      latex allergens and goldenrod proteins was studied using recombinant Hev b 1, 3,
      4, 5, 6.01, 6.02, 8, 9, or 11 in ImmunoCAP inhibition analyses. RESULTS:
      Immunoglobulin (Ig) E antibodies from individuals with goldenrod allergy bound
      extracted goldenrod proteins ranging from 20 kDa to 130 kDa in Western blots.
      Evidence for latex and goldenrod cross reactivity was identified by ImmunoCAP and
      immunoblot inhibition experiments using serum from patients with strongly
      positive concomitant latex and goldenrod-specific IgE antibody responses.
      Observed latex-goldenrod cross reactivity could not be ascribed to any of the
      recombinant major latex allergens evaluated. CONCLUSIONS: H brasiliensis latex
      and goldenrod contain cross-reactive and unique allergenic proteins. Exposure to
      goldenrod may sensitize patients to latex and vice versa.

PMID- 20815312
TI  - Polymorphisms in the toll-like receptor 2 subfamily and risk of asthma: a case
      control analysis in a Chinese population.
AB  - BACKGROUND AND OBJECTIVE: Cell activation through toll-like receptors (TLRs) has
      robust bipolar effects on host immunity and the pathogenesis of asthma. The TLR2
      subfamily is a pivotal member of the TLR family. We sought to determine whether
      mutations in TLR2 subfamily genes affect the risk of asthma. METHODS: A total of
      318 asthmatic patients and 352 nonasthmatic controls were recruited. Eight single
      nucleotide polymorphisms in TLR2 subfamily genes were detected using GenomeLab
      SNPstream (Beckman Coulter, Fullerton, California, USA). RESULTS: We found that
      patients with the TLR2/rs7656411 TT variant homozygote had a significantly
      reduced risk of asthma when compared with those with the GG wild-type homozygote
      (adjusted odds ratio [OR], 0.63; 95% confidence interval (CI], 0.41-0.98; P =
      .036). Furthermore, a positive association was observed between the T allele of
      rs2381289 in TLR6 and allergic rhinitis in asthma (OR, 1.79; 95% CI, 1.10-2.91; P
      = .025), while the A allele of rs11466651 in TLRIO was negatively associated with
      allergic rhinitis (OR, 0.49; 95% CI, 0.26-0.95; P = .046). CONCLUSION: Our
      results indicate that a genetic variant in the TLR2 subfamily may play a role in
      susceptibility to asthma.

PMID- 20815313
TI  - Anaphylactic reaction due to cyclopentolate in a 4-year-old child.
AB  - Ophthalmologists frequently use mydriatics both for diagnosis (retinal
      exploration, refraction tests) and for treatment. Cyclopentolate is used to
      induce quick and successful mydriasis for pediatric eye examination.
      Hypersensitivity reaction to cyclopentolate is very uncommon, especially in
      children. We report the case of a child who experienced a hypersensitivity
      reaction to cyclopentolate during preparation for an eye examination under
      cycloplegia.

PMID- 20815314
TI  - Occupational asthma caused by turbot allergy in 3 fish-farm workers.
AB  - We report 3 patients (26, 31, and 33 years) who worked at the same fish farm for
      several years. They experienced symptoms of rhinoconjunctivitis and bronchial
      asthma while classifying fish by size. Their asthma gradually worsened to the
      extent that it became persistent and required daily medication with inhaled
      corticosteroids and bronchodilators. Symptoms improved during weekends and
      holidays. All 3 patients could eat turbot. Our study showed that the patients
      were allergic and that sensitization was probably by inhalation. The allergens
      were parvalbumin in 1 case and a different allergen in the remaining 2 patients.

PMID- 20815315
TI  - Anaphylaxis due to Pachycondyla goeldii ant: a case report.

PMID- 20815316
TI  - A hidden cause of perioperative anaphylaxis.

PMID- 20815317
TI  - 2-phenoxyethanol-induced contact urticaria and anaphylaxis.

PMID- 20815318
TI  - Garlic-induced severe anaphylaxis in a nonatopic patient.

PMID- 20815319
TI  - Duration of breastfeeding and the risk of childhood asthma in children living in
      urban areas.

PMID- 20815320
TI  - Selective immunoglobulin M deficiency in a patient with refractory giardiasis.

PMID- 20815321
TI  - Immunoglobulin E-mediated anaphylaxis to rabeprazole.

PMID- 20815322
TI  - Exposure to risky concentrations of Dermatophagoides allergens in a high-altitude
      population (Quito, 2800 m above sea level in the Andean Mountains).

PMID- 20815323
TI  - Fungal colonization in nasal polyposis.

PMID- 20815324
TI  - Susceptibility of black bullhead Ameiurus melas to a panel of ranavirus isolates.
AB  - Ranaviruses are considered a serious threat to lower vertebrates, including fish,
      amphibians and reptiles. However, epidemiological data on these agents are
      lacking, and further investigations are needed to understand the role of carriers
      and to update the list of susceptible hosts. We carried out various experimental
      infections under controlled conditions to contribute to the current knowledge on
      the susceptibility of black bullhead Ameiurus melas to European catfish virus
      (ECV) and other ranaviruses. A panel of 7 ranavirus isolates was used to
      challenge duplicate groups of A. melas juveniles maintained in aquaria supplied
      with running dechlorinated tap water. The experiments were performed at 15 and 25
      degrees C. The results confirmed the high susceptibility of A. melas to ECV
      infection. Furthermore, a significant mortality associated with the typical signs
      of systemic viral infections was observed in groups challenged with Epizootic
      haematopoietic necrosis virus (EHNV) at 25 degrees C, and to a lesser extent, at
      15 degrees C. No significant mortality was recorded in fish challenged with
      European sheatfish virus (ESV), Frog virus 3 (FV3), Rana esculenta virus-like
      (REV-like), Bohle iridovirus (BIV) or short-finned eel virus (SERV).

PMID- 20815325
TI  - Interactions of virulent and avirulent Yersinia ruckeri strains with isolated
      gill arches and intestinal explants of rainbow trout Oncorhynchus mykiss.
AB  - Yersinia ruckeri is the causative agent of enteric redmouth disease leading to
      significant losses in salmonid aquaculture worldwide. Little information is
      available on the pathogenesis of this disease. Basic steps in the establishment
      of an infection include attachment to the epithelium followed by invasion at the
      portal of entry. In this study, the interactions of Y. ruckeri with the gills and
      the gut of rainbow trout Oncorhynchus mykiss (Walbaum, 1792) were studied using
      standardized perfusion models. Virulent and avirulent Y ruckeri isolates appeared
      to adhere to and invade both tissues without significant differences. For the
      first time, the gill and gut perfusion models are shown to be suitable to study
      bacterial invasiveness.

PMID- 20815326
TI  - Low prevalence of splenic mycobacteriosis in migratory striped bass Morone
      saxatilis from North Carolina and Chesapeake Bay, U.S.A.
AB  - Mycobacteriosis is a chronic bacterial disease causing an ongoing epizootic in
      striped bass Morone saxatilis in Chesapeake Bay, U.S.A. Prevalence of disease is
      high in pre-migratory fish, and multiple species of Mycobacterium spp. have been
      isolated. However, prevalence of mycobacteriosis in the coastal migratory
      population is unknown and is of concern to multiple coastal states, as disease
      related mortality may impact the long-term health of the population. Histological
      examinations of spleens collected from fish caught by recreational anglers during
      the winter fishery in coastal North Carolina (2005-2006, n=249) and during the
      spring fishery in Chesapeake Bay (2006, n=120) indicated a low prevalence of
      mycobacteriosis (6.8% of all fish examined) in comparison to smaller, pre
      migratory Chesapeake Bay fish. Genus-level PCR and subsequent sequencing of the
      16-23S intergenic transcribed spacer (ITS) region revealed that all bacteria were
      phylogenetically related, but species is unknown. Location of survey, gender of
      fish, and total length of fish had no significant effect on prevalence of
      mycobacteriosis, parasitic granulomas, or the density of splenic granulomas (p >
      0.05). These results may indicate that either granulomas resolve after Chesapeake
      Bay fish enter the coastal migratory population, or that there is disease-related
      mortality among pre-migratory Chesapeake Bay fish.

PMID- 20815327
TI  - Histopathological and ultrastructural studies on a novel pathological condition
      in Solea senegalensis.
AB  - A new parasitic disease affecting cultured sole Solea senegalensis (Kaup, 1858)
      is characterised by the presence of external protuberances in the skin of the
      affected fish. These lesions correspond to nodules in the muscular tissue showing
      an abscess-like aspect. Similar lesions were found in the kidney, heart, liver
      and digestive tract. Histological sections of these nodules revealed the presence
      of a large core formed mainly of necrotic tissue surrounded with fibroblasts and
      macrophages. Round-shaped plasmodial organisms were found in the external layer
      of the nodules and usually inside macrophages or fibroblasts. These organisms
      were also observed in the intestinal mucosa inside phagocytic cells or
      parasitophorous vacuoles within the enterocytes. The morphological and
      ultrastructural characteristics of these organisms are similar to the morphology
      of some groups of parasites described as fish pathogens. The main features
      suggest that these organisms could be amoebae or parasites with an amoeboid or
      plasmodial form in their developmental cycle.

PMID- 20815328
TI  - Tetracapsuloides bryosalmonae (Myxozoa: Malacosporea) portal of entry into the
      fish host.
AB  - The portal of entry and the penetration process of the myxozoan parasite
      Tetracapsuloides bryosalmonae are still poorly understood. In the present study,
      spores of T. bryosalmonae derived from the bryozoan host (malacospores) were
      activated chemically and mechanically to investigate their reaction after
      attachment to the fish host in vitro. Amoeboid movement of both sporoplasms was
      shown for the first time. The morphology of malacospores was assessed using
      scanning electron microscopy (SEM). Openings of the polar capsules and released
      polar filaments were visible. One sporoplasm was observed leaving the spore
      shell. Laboratory exposure experiments of juvenile rainbow trout Oncorhynchus
      mykiss to spores of T. bryosalmonae were also conducted. Single fish were
      incubated with 1000 to 2000 spores in 100 ml of water for 5 to 60 min.
      Immunohistochemically stained sections of skin and gills were examined using
      light microscopy, as well as ultra thin sections using transmission electron
      microscopy (TEM), to investigate attachment and early penetration. Whole fish and
      excised gills of fish exposed to a spore suspension were fixed and prepared for
      scanning electron microscopy. Attached and penetrating stages were found only on
      or in the gills, and not in the skin. Due to the low overall number of spores,
      only a few spores were found adjacent to the gill epithelium in TEM. No parasite
      stages were found on the samples used for SEM. These results indicate that the
      gills are the preferred entry loci for the amoeboid sporoplasms of T.
      bryosalmonae into the fish host.

PMID- 20815329
TI  - Ultrastructural characteristics and histological impacts of Myxobolus naffari
      (Myxozoa: Myxosporea) infecting Nile labeo Labeo niloticus (Osteichthyes:
      Cichlidae).
AB  - We describe the ultrastructural characteristics and histological impacts of
      Myxobolus naffari Abdel-Ghaffar et al., 1998, which infects the Nile fish Labeo
      niloticus. The prevalence of infection was 65%, with the maximum rate occurring
      during winter and a lower rate during summer. The histological impacts were
      manifested as a fusion of the gill epithelia, hyperplasia at the ends of the
      plasmodia, and atrophy of the external surface of the plasmodia. The
      ultrastructural study revealed that the plasmodial wall was composed of a single
      unit membrane and bound externally by a thick layer of collagen fibers. The
      earliest recognizable stage was the disporous pansporoblast. The development of
      the parasite was asynchronous, with mature and immature spores randomly
      distributed throughout the plasmodium.

PMID- 20815330
TI  - Expression of mutant protein p53 and Hsp70 and Hsp90 chaperones in cockles
      Cerastoderma edule affected by neoplasia.
AB  - High prevalence of disseminated neoplasia has been found in cockles Cerastoderma
      edule of Galicia (NW Spain). Disseminated neoplasia has been associated with high
      mortalities of various bivalve species. In vertebrates, proteins such as p53 and
      heat shock proteins (HSPs) play important roles in carcinogenesis. The protein
      p53 has been detected in neoplastic cells of bivalve molluscs such as Mytilus
      edulis, Mytilus trossulus, Mya arenaria, Spisula solidissima, Crassostrea
      rhizophorae and Crassostrea gigas. In this study, western blotting analyses were
      used to test the expression of Hsp70, Hsp90 and mutant p53 proteins in the cells
      and plasma of the haemolymph of cockles showing various intensities of neoplasia.
      Disseminated neoplasia was previously diagnosed by examination of stained
      haemolymph monolayers with light microscopy. In the present study, mutant p53 was
      detected in haemolymph cells of cockles diagnosed as affected by moderate and
      heavy neoplasia intensity, whereas it was not detected in cockles with either no
      or light neoplasia. The higher the neoplasia intensity, the higher the levels of
      Hsp70 and Hsp90. These proteins were not found in plasma. The results reveal the
      possible association between p53 and HSPs in neoplastic cells of cockles, which
      could prevent p53 from carrying out its functions, as occurs in human cancers.

PMID- 20815331
TI  - Mass mortality of cultured ascidians Halocynthia roretzi associated with
      softening of the tunic and flagellate-like cells.
AB  - Since 2007, mass mortalities of cultured ascidians Halocynthia roretzi (Drasche)
      have occurred in Miyagi Prefecture, Japan. The mortalities occur from November
      through August, and the tunics of affected animals become abnormally weak and
      soft. The number of farming areas where mass mortalities have occurred has
      increased rapidly: 3 in 2007, 6 in 2008, and 14 in 2009. When an outbreak of the
      disease occurred, mortality reached 17 to 100%. Prominent histopathological
      changes in the diseased ascidians were found in the tunics; the tunics of
      affected animals were usually much thinner than those of healthy individuals, and
      the tunic matrix showed marked disintegration with irregular arrangements of
      fiber layers or the presence of hollow spaces. In addition, flagellate-like cells
      (10-14 microm x 2-3 microm) stained with hematoxylin were observed in the tunics
      of 31 out of 36 diseased animals (86%), but not in apparently healthy animals
      (n=38). Experimental infection with the disease was successfully conducted by
      immersing small pieces of tunic samples from diseased ascidians into aquaria with
      healthy ascidians. The flagellate-like cells were confirmed in the tunics of all
      the experimentally infected animals. These results indicate that the mass
      mortalities of ascidians accompanied by abnormally softened tunics were caused by
      an infectious agent, and suggest the involvement of the flagellate-like cells in
      the disease.

PMID- 20815332
TI  - Detection of megalocytivirus from imported tropical ornamental fish, paradise
      fish Macropodus opercularis.
AB  - Megalocytivirus was detected from paradise fish Macropodus opercularis imported
      from Indonesia. Four of 11 fish (36%) in 2006 and 40 of 117 fish (34%) in 2008
      were found to be PCR-positive for megalocytivirus. Phylogenetic analysis based on
      partial major capsid protein (MCP) gene nucleotide sequences revealed that the
      sequences detected in paradise fish were classified as Genotype II, which
      includes freshwater fish isolates from Southeast Asian countries, closely related
      to infectious spleen and kidney necrosis virus (ISKNV), Murray cod iridovirus
      (MCIV), and dwarf gourami iridovirus (DGIV-2004). Paradise fish was added as a
      new host for megalocytivirus based on this study.

PMID- 20815333
TI  - Diphenyl(1-naphthyl)phosphine ancillary for assembling of red and orange-emitting
      Ir(III) based phosphors; strategic synthesis, photophysics, and organic light
      emitting diode fabrication.
AB  - Treatment of a series of dinuclear Ir(III) complexes [(fnazo)(2)Ir(MU-Cl](2),
      [(fpiq)(2)Ir(MU-Cl](2), and [(fppy)(2)Ir(MU-Cl](2) with diphenyl(1
      naphthyl)phosphine (dpnH) in decalin at 100  degrees C afforded the simple
      adducts, trans-N,N'-[(fnazo)(2)Ir(dpnH)Cl] (1a), trans-N,N'-[(fpiq)(2)Ir(dpnH)Cl]
      (1b), and trans-N,N'-[(fppy)(2)Ir(dpnH)Cl] (1c), for which the C(?)N
      cyclometalating reagents, that is, fnazoH, fpiqH and fppyH, stands for 4-(4
      fluorophenyl)quinazoline, 1-(4-fluorophenyl)isoquinoline and 4
      fluorophenylpyridine, respectively. Single crystal X-ray diffraction study on 1a
      revealed existence of two trans-N,N' cyclometalates, with both chloride and dpnH
      donors located at the positions opposite to the phenyl substituents. Subsequent
      heating of 1a-1c at higher temperature afforded the second isomer (2a-2c),
      showing formation of cis-N,N' orientation for the aforementioned cyclometalates.
      Further thermolysis of either trans or cis-Ir(III) complexes 1 or 2 in presence
      of sodium acetate, which serves as both activator and chloride scavenger, gave
      successful isolation of a mixture of two fully cyclometalated Ir(III) complexes
      trans-N,N'-[(C(?)N)(2)Ir(dpn)] (3a-3c) and cis-N,N'-[(C(?)N)(2)Ir(dpn)] (4a-4c).
      Structural and photophysical properties of complexes 3a-3c and 4a-4c were
      measured and compared. Time-dependent density functional theory (DFT) studies
      suggested that, upon changing the C(?)N cyclometalates from quinazolinyl,
      isoquinolinyl, and, finally, to pyridyl fragment, the lowest unoccupied molecular
      orbitals (LUMOs) are gradually shifted from the cyclometalating nitrogen
      heterocycles to the 1-naphthyl group of the phosphine chelate and, concomitantly
      altered the photophysical properties. An organic light-emitting diode (OLED)
      using orange-red phosphors 4a and 4b has been successfully fabricated. At the
      practical brightness of 500 cd.m(-2), decent external quantum efficiency of 10.6%
      and 12.5% could be reached for 4a and 4b, respectively, revealing the usefulness
      of relevant molecular architecture in designing triplet OLED emitters.

PMID- 20815334
TI  - Sub-100 nm channel length graphene transistors.
AB  - Here we report high-performance sub-100 nm channel length graphene transistors
      fabricated using a self-aligned approach. The graphene transistors are fabricated
      using a highly doped GaN nanowire as the local gate with the source and drain
      electrodes defined through a self-aligned process and the channel length defined
      by the nanowire size. This fabrication approach allows the preservation of the
      high carrier mobility in graphene and ensures nearly perfect alignment between
      source, drain, and gate electrodes. It therefore affords transistor performance
      not previously possible. Graphene transistors with 45-100 nm channel lengths have
      been fabricated with the scaled transconductance exceeding 2 mS/MUm, comparable
      to the best performed high electron mobility transistors with similar channel
      lengths. Analysis of and the device characteristics gives a transit time of 120
      220 fs and the projected intrinsic cutoff frequency (f(T)) reaching 700-1400 GHz.
      This study demonstrates the exciting potential of graphene based electronics in
      terahertz electronics.

PMID- 20815335
TI  - Supramolecular isomerism in honeycomb metal-organic frameworks driven by CH...pi
      interactions: homochiral crystallization from an achiral ligand through chiral
      inducement.
AB  - The solvothermal reaction of Zn(NO(3))(2).6H(2)O and 4,4',4''-(2,4,6
      trimethylbenzene-1,3,5-triyl)tribenzoic acid (H(3)TMTA) in N,N'-diethylformamide
      or N,N-dimethylacetamide gave rise to two layered honeycomb frameworks. The
      different stacking arrangements of the 2D layers generate achiral (alpha-1) and
      chiral (beta-1) architectures, which are supramolecular isomers. The homochiral
      crystallization of beta-1 can be achieved through chiral inducement, which is
      confirmed by circular dichroism spectra.

PMID- 20815336
TI  - Aptamer-based electrochemical biosensor for interferon gamma detection.
AB  - In this paper, we describe the development of an electrochemical DNA aptamer
      based biosensor for detection of interferon (IFN)-gamma. A DNA hairpin containing
      IFN-gamma-binding aptamer was thiolated, conjugated with methylene blue (MB)
      redox tag, and immobilized on a gold electrode by self-assembly. Binding of IFN
      gamma caused the aptamer hairpin to unfold, pushing MB redox molecules away from
      the electrode and decreasing electron-transfer efficiency. The change in redox
      current was quantified using square wave voltammetry (SWV) and was found to be
      highly sensitive to IFN-gamma concentration. The limit of detection for optimized
      biosensor was 0.06 nM with linear response extending to 10 nM. This aptasensor
      was specific to IFN-gamma in the presence of overabundant serum proteins.
      Importantly, the same aptasensor could be regenerated by disrupting aptamer-IFN
      gamma complex in urea buffer and reused multiple times. Unlike standard sandwich
      immunoassays, the aptasensor described here allowed one to detect IFN-gamma
      binding directly without the need for multiple washing steps and reagents. An
      electrochemical biosensor for simple and sensitive detection of IFN-gamma
      demonstrated in this paper will have future applications in immunology, cancer
      research, and infectious disease monitoring.

PMID- 20815337
TI  - Development and characterization of a GC-enabled QLT-Orbitrap for high-resolution
      and high-mass accuracy GC/MS.
AB  - We detail the development and characterization of a GC/QLT-Orbitrap hybrid mass
      spectrometer capable of high resolution (up to 100,000 at m/z 400) and sub-parts
      per-million mass accuracy GC/MS. A high-duty cycle, innovative scan type, the
      nested scan, was implemented to synchronize the Orbitrap acquisition rate and the
      time scale of gas chromatography (up to 6.5 Hz at resolution 7500). We benchmark
      this instrument's key figures of merit, including resolution, mass accuracy,
      linear dynamic range, and spectral accuracy, and demonstrate its performance for
      two challenging applications: the determination of polychlorinated dibenzo-p
      dioxins (PCDD) and dibenzofurans (PCDF) in environmental samples and the
      profiling of primary metabolites in Arabidopsis thaliana extracts.

PMID- 20815338
TI  - Quenched substrates for live-cell labeling of SNAP-tagged fusion proteins with
      improved fluorescent background.
AB  - Recent developments in fluorescence microscopy raise the demands for bright and
      photostable fluorescent tags for specific and background free labeling in living
      cells. Aside from fluorescent proteins and other tagging methods, labeling of
      SNAP-tagged proteins has become available thereby increasing the pool of
      potentially applicable fluorescent dyes for specific labeling of proteins. Here,
      we report on novel conjugates of benzylguanine (BG) which are quenched in their
      fluorescence and become highly fluorescent upon labeling of the SNAP-tag, the
      commercial variant of the human O(6)-alkylguanosyltransferase (hAGT). We
      identified four conjugates showing a strong increase, i.e., >10-fold, in
      fluorescence intensity upon labeling of SNAP-tag in vitro. Moreover, we screened
      a subset of nine BG-dye conjugates in living Escherichia coli and found them all
      suited for labeling of the SNAP-tag. Here, quenched BG-dye conjugates yield a
      higher specificity due to reduced contribution from excess conjugate to the
      fluorescence signal. We further extended the application of these conjugates by
      labeling a SNAP-tag fusion of the Tar chemoreceptor in live E. coli cells and the
      eukaryotic transcription factor STAT5b in NIH 3T3 mouse fibroblast cells. Aside
      from the labeling efficiency and specificity in living cells, we discuss possible
      mechanisms that might be responsible for the changes in fluorescence emission
      upon labeling of the SNAP-tag, as well as problems we encountered with
      nonspecific labeling with certain conjugates in eukaryotic cells.

PMID- 20815339
TI  - A biosensor study indicating that entropy, electrostatics, and receptor
      glycosylation drive the binding interaction between interleukin-7 and its
      receptor.
AB  - The interaction between interleukin-7 (IL-7) and its alpha-receptor, IL-7Ralpha,
      plays fundamental roles in the development, survival, and homeostasis of B- and T
      cells. N-Linked glycosylation of human IL-7Ralpha enhances its binding affinity
      for human IL-7 300-fold versus that of the nonglycosylated receptor through an
      allosteric mechanism. The N-glycans of IL-7Ralpha do not participate directly in
      the binding interface with IL-7. This biophysical study involves dissection of
      the properties of binding of IL-7 to both nonglycosylated and glycosylated forms
      of the IL-7Ralpha extracellular domain (ECD) as functions of salt, pH, and
      temperature using surface plasmon resonance (SPR) spectroscopy. Interactions of
      IL-7 with both IL-7Ralpha variants display weaker binding affinities with
      increasing salt concentrations primarily reflected by changes in the first on
      rates of a two-step reaction pathway. The electrostatic parameter of the IL-7-IL
      7Ralpha interaction is not driven by complementary charge interactions through
      residues at the binding interface or N-glycan composition of IL-7Ralpha, but
      presumably by favorable global charges of the two proteins. van't Hoff analysis
      indicates both IL-7-IL-7Ralpha interactions are driven by large favorable entropy
      changes and smaller unfavorable (nonglycosylated complex) and favorable
      (glycosylated complex) enthalpy changes. Eyring analysis of the IL-7-IL-7Ralpha
      interactions reveals different reaction pathways and barriers for the transition
      state thermodynamics with the enthalpy and entropy changes of IL-7 binding to
      nonglycosylated and glycosylated IL-7Ralpha. There were no discernible heat
      capacity changes for the equilibrium or transition-state binding thermodynamics
      of the IL-7-IL-7Ralpha interactions. The results suggest that the unbound
      nonglycosylated IL-7Ralpha samples an extensive conformational landscape relative
      to the unbound glycosylated IL-7Ralpha, potentially explaining the switch from a
      "conformationally controlled" reaction (k(1) ~ 10(2) M(-1) s(-1)) for the
      nonglycosylated interaction to a "diffusion-controlled" reaction (k(1) ~ 10(6) M(
      1) s(-1)) for the glycosylated interaction. Thus, a large favorable entropy
      change, a global favorable electrostatic component, and glycosylation of the
      receptor, albeit not at the interface, contribute significantly to the
      interaction between IL-7 and the IL-7Ralpha ECD.

PMID- 20815340
TI  - Isotopic effect on ion mobility and separation of isotopomers by high-field ion
      mobility spectrometry.
AB  - Distinguishing and separating isotopic molecular variants is important across
      many scientific fields. However, discerning such variants, especially those
      producing no net mass difference, has been challenging. For example, single-stage
      mass spectrometry is broadly employed to analyze isotopes but is blind to
      isotopic isomers (isotopomers) and, except at very high resolution, species of
      the same nominal mass (isobars). Here, we report separation of isotopic ions,
      including isotopomers and isobars, using ion mobility spectrometry (IMS),
      specifically, the field asymmetric waveform IMS (FAIMS). The effect is not based
      on the different reduced masses of ion-gas molecule pairs previously theorized to
      cause isotopic separations in conventional IMS, but appears related to the
      details of energetic ion-molecule collisions in strong electric fields. The
      observed separation qualitatively depends on the gas composition and may be
      improved using gas mixtures. Isotopic shifts depend on the position of the
      labeled site, which allows its localization and contains information about the
      ion geometry, potentially enabling a new approach to molecular structure
      characterization.

PMID- 20815341
TI  - Identification of a new antidepressant and its glucuronide metabolite in water
      samples using liquid chromatography/quadrupole time-of-flight mass spectrometry.
AB  - This paper reports the first detections of an antidepressant, lamotrigine, and
      its major metabolite (2-N-glucuronide), in environmental water samples using a
      new chlorine mass-filter technique with accurate mass and high resolution. A
      quantitative method is described using solid phase extraction (SPE) followed by
      liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/Q-TOF-MS)
      for the simultaneous analysis of both compounds in aqueous samples, including
      drinking water, groundwater, surface water, and wastewater collected from sewage
      treatment plants. The recoveries of the analytes ranged from 75 to 99%, depending
      on the type of water extracted. The method detection limits were 1 and 5 ng/L for
      lamotrigine and its metabolite, respectively. The method was validated with more
      than a hundred aqueous samples analyzed and lamotrigine and its 2-N-glucuronide
      metabolite were mostly detected in both wastewater and surface water impacted
      sites at mean concentrations of 488 and 209 ng/L, respectively. Lamotrigine was
      detected in 94% of all the wastewater samples analyzed. Two detections for
      lamotrigine occurred in drinking water. To our knowledge, this is the first
      report of water samples containing lamotrigine, a relatively new drug used for
      the treatment of epilepsy and type I bipolar syndrome. It is also the first
      report of a glucuronide of an antidepressant surviving wastewater treatment plant
      operations and becoming a ground and surface water contaminant.

PMID- 20815342
TI  - Proteomic analysis of heat shock-induced protection in acute pancreatitis.
AB  - Acute pancreatitis is an inflammatory disease of the pancreas, which can result
      in serious morbidity or death. Acute pancreatitis severity can be reduced in
      experimental models by preconditioning animals with a short hyperthermia prior to
      disease induction. Heat shock proteins 27 and 70 are key effectors of this
      protective effect. In this study, we performed a comparative proteomic analysis
      using a combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      analysis and isobaric tagging to investigate changes in pancreatic proteins
      expression that were associated with thermal stress, both in healthy rats and in
      a model of caerulein-induced pancreatitis. In agreement with previous studies, we
      observed modulation of heat shock and inflammatory proteins expression in
      response to heat stress or pancreatitis induction. We also identified numerous
      other proteins, whose pancreatic level changed following pancreatitis induction,
      when acute pancreatitis severity was reduced by prior thermal stress, or in
      healthy rats in response to hyperthermia. Interestingly, we showed that the
      expression of various proteins associated with the secretory pathway was modified
      in the different experimental models, suggesting that modulation of this process
      is involved in the protective effect against pancreatic tissue damage.

PMID- 20815343
TI  - Nickel-catalyzed alkenylative cross-coupling reaction of alkyl sulfides.
AB  - A novel cross-coupling reaction of alkyl aryl sulfides with aryl Grignard
      reagents has been achieved to produce the alkenyl-aryl coupling products in high
      yields by using catalytic Ni(cod)(2) and a bulky N-heterocyclic carbene ligand,
      SIPr.

PMID- 20815344
TI  - In-water truly monodisperse aggregation of gear-shaped amphiphiles based on
      hydrophobic surface engineering.
AB  - Exactly six gear-shaped amphiphiles self-assemble into a highly stable, water
      soluble, box-shaped capsule, in which indented hydrophobic surfaces of the
      components mesh with each other like gears. A water-soluble, tetrahedron-shaped
      capsule was also constructed from four gear-shaped amphiphiles with a template
      guest. These findings provide a guideline for creating aggregates with a given
      number of amphiphiles based on hydrophobic surface engineering.

PMID- 20815345
TI  - Hydroxyapatite foam as a catalyst for formaldehyde combustion at room
      temperature.
AB  - The excellent performance of hydroxyapatite, a novel non-precious metal catalyst,
      for formaldehyde (HCHO) combustion at room temperature is reported. Temperature
      programmed surface reaction results indicated that hydroxyl groups bonded with
      the channel Ca(2+) may be responsible for adsorption/activation of HCHO.

PMID- 20815346
TI  - Pneumatically pumping fluids radially inward on centrifugal microfluidic
      platforms in motion.
AB  - This paper describes a pumping technique applicable to centrifugal microfluidic
      platforms, involving the use of a regulated stream of compressed gas to pump
      liquid radially inward and toward the center of the platform while spinning. This
      technique provides a noncontact method for pumping fluids and is highly
      efficient, requiring only approximately 60 s to reach completion. This pumping
      operation can be attained with an applied gas flow rate of 58.8 L min(-1), while
      the platform is rotated at frequencies less than 180 rpm (3.0 Hz).

PMID- 20815347
TI  - Survey of materials for nanoskiving and influence of the cutting process on the
      nanostructures produced.
AB  - This paper examines the factors that influence the quality of nanostructures
      fabricated by sectioning thin films with an ultramicrotome ("nanoskiving"). It
      surveys different materials (metals, ceramics, semiconductors, and conjugated
      polymers), deposition techniques (evaporation, sputter deposition, electroless
      deposition, chemical-vapor deposition, solution-phase synthesis, and spin
      coating), and geometries (nanowires or two-dimensional arrays of rings and
      crescents). It then correlates the extent of fragmentation of the nanostructures
      with the composition of the thin films, the methods used to deposit them, and the
      parameters used for sectioning. There are four major conclusions. (i) Films of
      soft and compliant metals (those that have bulk values of hardness less than or
      equal to those of palladium, or <=500 MPa) tend to remain intact upon sectioning,
      whereas hard and stiff metals (those that have values of hardness greater than or
      equal to those of platinum, or >=500 MPa) tend to fragment. (ii) All conjugated
      polymers tested form intact nanostructures. (iii) The extent of fragmentation is
      lowest when the direction of cutting is perpendicular to the exposed edge of the
      embedded film. (iv) The speed of cutting-from 0.1 to 8 mm/s-has no effect on the
      frequency of defects. Defects generated during sectioning include scoring from
      defects in the knife, delamination of the film from the matrix, and compression
      of the matrix. The materials tested were: aluminum, titanium, nickel, copper,
      palladium, silver, platinum, gold, lead, bismuth, germanium, silicon dioxide
      (SiO2), alumina (Al2O3), tin-doped indium oxide (ITO), lead sulfide nanocrystals,
      the semiconducting polymers poly(2-methoxy-5-(2'-ethyl-hexyloxy)-1,4-phenylene
      vinylene) (MEH-PPV), poly(3-hexylthiophene) (P3HT), and
      poly(benzimidazobenzophenanthroline ladder) (BBL), and the conductive polymer
      poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS).

PMID- 20815348
TI  - Water: nature's reaction enforcer--comparative effects for organic synthesis "in
      water" and "on-water".

PMID- 20815349
TI  - Production, stability, and antioxidative and antimicrobial activities of two L
      ascorbate analogues from phycomyces blakesleeanus: D-erythroascorbate and D
      erythroascorbate glucoside.
AB  - D-erythroascorbate (D-EAA), a five-carbon analogue of L-ascorbate (L-AA), and D
      erythroascorbate monoglucoside (D-EAAG) are accumulated in Phycomyces
      blakesleeanus grown on glucose (99.5 and 1084 MUg/g mycelial dry weight,
      respectively) and also excreted into the culture medium. Both compounds showed UV
      spectral properties and ionization constants similar to those of L-AA. D-EAAG was
      much more stable to aerobic oxidation than D-EAA and L-AA at acidic pH. D-EAAG is
      synthesized from D-erythroascorbate by a mycelial glucosyltransferase activity
      that uses UDP-glucose as glucose substrate donor with K(m) = 2.5 mM and 41.3 MUM
      for D-EAA. This glucosyltransferase activity was maximal in the stationary growth
      phase in parallel with maximal production of D-EAAG. The presence of D-arabinose
      or D-arabinono-1,4-lactone in the culture medium produces the maximal
      accumulation of D-EAA and D-EAAG (about 30- and 4-fold with respect to that
      obtained in glucose culture). Both compounds showed greater antioxidant activity
      than L-AA and other standard antioxidants, with a capacity similar to that of L
      AA to inhibit the growth of Escherichia coli.

PMID- 20815350
TI  - Sensitive DNA-based electrochemical strategy for trace bleomycin detection.
AB  - Bleomycins (BLMs) are widely used in combination with chemotherapy for the
      treatment of a variety of cancers. The clinical application of BLMs is featured
      by the occurrence of sometimes fatal side effects, such as renal and lung
      toxicity, and the potential dose-limiting side effect of pulmonary fibrosis.
      Therefore, it is highly desirable to develop a sensitive method to quantitatively
      determine the BLM content in both pharmaceutical analysis and clinical samples,
      to make full use of therapeutic efficacy and to weaken its toxicity. Here, we
      proposed a simple, rapid, and convenient electrochemical assay for trace BLM
      detection. A reported DNA motif, as substrate for BLMs, is prepared to self
      assemble onto the gold electrode to fabricate an electrochemical DNA (E-DNA)
      sensor, with a terminus tethered on the electrode surface and the other terminus
      labeled with ferrocenyl moiety as a signal reporter to form a stem-loop
      structure, giving an arise of remarkable faradaic current. In the presence of
      Fe(II).BLM, the E-DNA sensor undergoes the irreversible cleavage event, which can
      be transduced into a significant decrease in current peak. This proposed sensor
      reveals an impressive sensitivity as low as 100 pM BLMs and exhibits a good
      performance as well as in serum sample. Considering the high sensitivity and
      specificity of this proposed sensor, as well as the cost-effective and simple-to
      implement features of the electrochemical technique, we believe that this method
      shows distinct advantages over conventional methods and it is a promising
      alternative for the determination of trace amounts of BLMs in clinical samples.

PMID- 20815351
TI  - The influence of environment on terahertz spectra of biological molecules.
AB  - The variability of molecular vibrations and low terahertz spectra of biological
      molecules depending on the three-dimensional structure of molecular clusters,
      chemical bonding, and molecular concentration in the surrounding media is studied
      using computer simulations. The resonant terahertz spectra of biological
      molecules and their associations are described within the framework of molecular
      mechanics using an all-atom molecular mechanical force field for proteins and
      nucleic acids. Both the absolute values of absorption coefficients and their
      spectral properties are considered for murein-lipoprotein and thioredoxin of E.
      coli and models of bacterial DNAs using energy minimization and molecular
      dynamics. The obtained results indicate that structural changes introduced by
      chemical reactions and molecule associations can strongly affect terahertz
      spectra, causing significant changes in absorption peak intensities and shifts in
      peak positions. Terahertz light absorption intensities of studied proteins are
      predicted to be strongly affected by solvents.

PMID- 20815352
TI  - Morton lentil extract attenuated angiotensin II-induced cardiomyocyte hypertrophy
      via inhibition of intracellular reactive oxygen species levels in vitro.
AB  - The objective was to investigate whether a lentil (Morton) extract had any
      protective effect on cardiac hypertrophy, which is one of the most significant
      sequelae of cardiovascular diseases. High phenolic compounds (43.4 mg of GAE/g),
      including thirteen phenolic acid and two flavonoids, were detected in the
      acetone/water/acetic acid lentil extract. The extract showed strong antioxidant
      ability (105 MUmol of TE/g). The effect of lentil extract on angiotensin (Ang) II
      induced cardiac hypertrophy was examined. Results showed that pretreatment with
      lentil extract (25, 50, 100 MUg/mL) significantly attenuated Ang II (0.1 MUM)
      induced hypertrophy by 18, 28, and 36% in rat cardiomycytes, respectively; lentil
      extract (12.5, 25, 50 MUg/mL) attenuated Ang II (0.1 MUM)-induced hypertrophy by
      9, 17, and 25% in human cardiomycytes, respectively. Intracellular reactive
      oxygen species (ROS) levels were enhanced by Ang II treatment, and this
      stimulatory action was significantly attenuated (33% inhibition) by lentil
      extract (100 MUg/mL) in rat cardiomyocytes and attenuated by 22% by 50 MUg/mL
      lentil extract in human cardiomyocytes. In conclusion, Morton lentil extracts
      attenuated Ang II-induced rat and human cardiomyocytes hypertrophy via decreasing
      intracellular ROS levels.

PMID- 20815353
TI  - Purification and characterization of novel glucanases from Trichoderma harzianum
      ETS 323.
AB  - Trichoderma harzianum ETS 323 secretes two glucanases, a 23.5 kDa endoglucanase
      (EG Th1) and a 61 kDa exoglucanase (ExG Th1). They were identified by their
      hydrolysis products and were purified to homogeneity. The optimal temperature and
      pH for both EG Th1 (7.3-fold purification, 5.0% yield) and ExG Th1 (33.7-fold
      purification, 0.15% yield) were 50  degrees C and pH 4.5, respectively. The
      kinetic parameters of EG Th1 (K(m) = 23 mg mL(-1), V(max) = 294 MUM min(-1),
      specific activity = 7.4 U mg(-1)) and ExG Th1 (K(m) = 85 mg mL(-1), V(max) = 385
      MUM min(-1), specific activity = 24.6 U mg(-1)) toward carboxymethyl cellulose
      were determined. Both enzymes favored CMC and maintained 100% activity for 10
      days at 38  degrees C. KCl, MgCl(2), HgCl(2), and FeCl(3) showed approximately
      30% inhibition against EG Th1 but not ExG Th1. They catalyzed transglycosylation
      of glucose in the presence of cellobiose, but ExG Th1 exhibited better activity
      and higher product diversity.

PMID- 20815354
TI  - Structural dynamics of clamshell rotation during the incipient relaxation process
      of photodissociated carbonmonoxy myoglobin: statistical analysis by the
      perturbation ensemble method.
AB  - The structural dynamics of the clamshell rotation of photodissociated
      carbonmonoxy myoglobin, which is expected to be important for hemoglobin
      allostery, is investigated by the perturbation ensemble method. In this method,
      many pairs of perturbed and unperturbed molecular dynamics trajectories are
      ensemble-averaged to cancel out thermal noises and to detect subtle changes. The
      number of MD trajectory pairs, in this work 2000 pairs, should be determined to
      obtain physical properties of interest with statistically meaningful precisions.
      The calculated structural changes after 20 ps of the photodissociation are
      consistent with those by time-resolved X-ray diffraction at 100 ps delay time. In
      the heme proximal side region including the F and H helices, both helices
      displaced in the proximal direction. Meanwhile, in the heme distal side region
      including E and A helices, both helices moved toward the heme group after
      photodissociation. These proximal and distal side displacements occur on a fast
      time scale (almost complete within 3 ps) and are consistent with the clamshell
      rotation. Moreover, it was found that the ensemble-averaged structural dynamics
      of the photodissociated MbCO is independent of the amount of initial excess
      vibrational energy of the heme, or the difference of excitation photon
      wavelength. These results provide atomistic details on the functionally important
      dynamics of the clamshell rotation. Application of the present methodology to Hb
      will give new insight into the incipient stereochemical mechanism of hemoglobin
      allostery.

PMID- 20815355
TI  - Triacetone triperoxide (TATP): hapten design and development of antibodies.
AB  - Triacetone triperoxide (TATP), an improvised explosive, is a potential security
      threat because of its cost-efficient synthesis and the difficulty in detecting
      it. A highly selective antibody could provide the necessary specificity to the
      detection process. To obtain antibodies, a hapten made from acetone, hydrogen
      peroxide, and 7-oxooctanoic acid has been designed, synthesized, and confirmed by
      NMR that displays the utmost similarity to the analyte. The single-crystal X-ray
      structures of the solvated species TATP.methanol (1:1) and the TATP derivate were
      determined. In both compounds, the molecules exhibit D(3) symmetry and adopt a
      twisted boat-chair conformation. The hapten was coupled to bovine serum albumin,
      and mice were immunized. An immune response against TATP was elicited, and
      selective antibodies were detected in the mouse serum, which should be very
      useful for the development of a TATP biosensor system. An ELISA with a limit of
      detection for TATP of 65 MUg L(-1) is shown.

PMID- 20815356
TI  - Comparing contact angle measurements and surface tension assessments of solid
      surfaces.
AB  - Four types of contact angles (receding, most stable, advancing, and "static")
      were measured by two independent laboratories for a large number of solid
      surfaces, spanning a large range of surface tensions. It is shown that the most
      stable contact angle, which is theoretically required for calculating the Young
      contact angle, is a practical, useful tool for wettability characterization of
      solid surfaces. In addition, it is shown that the experimentally measured most
      stable contact angle may not always be approximated by an average angle
      calculated from the advancing and receding contact angles. The "static" CA is
      shown in many cases to be very different from the most stable one. The measured
      contact angles were used for calculating the surface tensions of the solid
      samples by five methods. Meaningful differences exist among the surface tensions
      calculated using four previously known methods (Owens-Wendt, Wu, acid-base, and
      equation of state). A recently developed, Gibbsian-based correlation between
      interfacial tensions and individual surface tensions was used to calculate the
      surface tensions of the solid surfaces from the most stable contact angle of
      water. This calculation yielded in most cases higher values than calculated with
      the other four methods. On the basis of some low surface energy samples, the
      higher values appear to be justified.

PMID- 20815358
TI  - Inhibition by CO and polarization in Pd-based membranes: a novel permeation
      reduction coefficient.
AB  - In this Article, a novel permeation reduction coefficient (PRC) is defined and
      used to take into account the presence of both inhibition by CO and concentration
      polarization in hydrogen permeation through Pd-based membranes. The usefulness of
      this coefficient consists in the possibility of describing simply, but at the
      same time powerfully, the behavior of the membrane subject to the combined effect
      of inhibition and polarization. According to this approach, the effective
      permeance, which is generally unknown because it depends on these two phenomena,
      can be directly evaluated by multiplying the "clean" intrinsic membrane Sieverts
      permeance (measurable by simple pure hydrogen permeation tests) by a PRC
      function, that is, [effective permeance] = (1-PRC) [clean Sieverts permeance].
      The values of PRC are evaluated by means of a complex model that takes into
      account the several elementary permeation steps, in which the inhibitory effect
      of CO is also considered as well as the concentration polarization. The membrane
      behavior is evaluated in terms of some "performance maps", where PRC and other
      two coefficients (concentration polarization coefficient (CPC) and inhibition
      coefficient (IC)) are reported as functions of several operating conditions
      (hydrogen molar fraction, CO partial pressure, and upstream total pressures).
      Therefore, these maps provide a useful tool to estimate directly the main design
      parameter (the overall permeance) in situations where complex transport and
      kinetic phenomena affect the membrane performances, allowing the membrane
      performance to be estimated much better and the separation equipment to be better
      designed.

PMID- 20815359
TI  - BODIPY-based chain transfer agent: reversibly thermoswitchable luminescent gold
      nanoparticle stabilized by BODIPY-terminated water-soluble polymer.
AB  - Well-defined poly(N-isopropylacrylamide)s (PNIPAMs) with boron dipyrromethene
      (BODIPY) in the terminal end were prepared by reversible addition-fragmentation
      chain transfer (RAFT) polymerization of NIPAM with BODIPY-chain transfer agent
      (CTA), which was synthesized by the reaction of pyrrole and BODIPY derivative
      having benzyl chloride in the meso position. The controlled character of the
      polymerization of NIPAM was confirmed by the formation of the narrow molecular
      weight distribution products and linear increase of molecular weight with the
      feed ratios of [NIPAM]/[CTA]. The RAFT-prepared PNIPAM exhibited strong green
      luminescence with emission maxima at 558 nm upon excitation with the absorption
      maxima at 526 nm and was used for the aqueous synthesis of stabilized gold
      nanoparticles (AuNPs). The in situ reduction of the RAFT-prepared polymers and
      HAuCl(4) resulted in the formation of stable modified AuNPs with size
      distributions of ~10 nm in water solution. Temperature-dependent change in
      photoluminescence (PL) spectra (excited at 526 nm) of the RAFT-prepared polymers
      measured in water showed an increase in emission intensity with the rise at
      temperature (20 -> 40  degrees C). On the contrary, AuNPs exhibited a decrease in
      emission intensity with increasing of temperature, resulting that shrinking of
      the distance between BODIPY units and Au core in the AuNP across border LCST
      gives rise to both quenching of emission of BODIPY unit by Forster resonance
      energy transfer (FRET) and dye quenching of aggregated BODIPY units. The
      emission/quenching of AuNP occurs reversibly and efficiently, regardless of the
      heating and cooling cycle.

PMID- 20815357
TI  - The role of Zn2+ on the structure and stability of murine adenosine deaminase.
AB  - Adenosine deaminase (ADA) is a key enzyme in purine metabolism and crucial for
      normal immune competence. It is a 40 kDa monomeric TIM-barrel protein containing
      a tightly bound Zn(2+), which is required for activity. In this study, we have
      investigated the role of Zn(2+) with respect to ADA structure and stability.
      After removing Zn(2+), the crystallographic structure of the protein remains
      highly ordered and similar to that of the holo protein with structural changes
      limited to regions capping the active site pocket. The stability of the protein,
      however, is decreased significantly in the absence of Zn(2+). Denaturation with
      urea shows the midpoint to be about 3.5 M for the apo enzyme, compared with 6.4 M
      for the holo enzyme. ADA contains four tryptophan residues distant from the
      Zn(2+) site. (19)F NMR studies in the presence and absence of Zn(2+) were carried
      out after incorporation of 6-(19)F-tryptophan. Chemical shift differences were
      observed for three of the four tryptophan residues, suggesting that, in contrast
      to the X-ray data, Zn(2+)-induced structural changes are propagated throughout
      the protein. Changes throughout the structure as suggested by the NMR data may
      explain the lower stability of the Zn(2+)-free protein. Real-time (19)F NMR
      spectroscopy measuring the loss of Zn(2+) showed that structural changes
      correlated with the loss of enzymatic activity.

PMID- 20815360
TI  - Ultrafast excited-state dynamics and photolysis in base-off B12 coenzymes and
      analogues: absence of the trans-nitrogenous ligand opens a channel for rapid
      nonradiative decay.
AB  - Ultrafast transient absorption spectroscopy was used to investigate the
      photochemistry of adenosylcobalamin (AdoCbl), methylcobalamin (MeCbl), and n
      propylcobalamin (PrCbl) at pH 2 where the axial nitrogenous ligand is replaced by
      a water molecule. The evolution of the difference spectrum reveals the internal
      conversion process and spectral characteristics of the S(1) excited state. The
      photolysis yield in the base-off cobalamins is controlled by competition between
      internal conversion and bond homolysis. This is in direct contrast to the process
      in most base-on alkylcobalamins where primary photolysis occurs with near unit
      quantum yield and the photolysis yield is controlled by competition between
      diffusive separation of the radical pair and geminate recombination. The absence
      of the axial nitrogenous ligand in the base-off cobalamins modifies the
      electronic structure and opens a channel for fast nonradiative decay. This
      channel competes effectively with the channel for bond dissociation, dropping the
      quantum yield for primary radical pair formation from unity in base-on PrCbl and
      AdoCbl to 0.2 +/- 0.1 and 0.12 +/- 0.06 in base-off PrCbl and AdoCbl,
      respectively. The photolysis of base-off MeCbl is similar to that of base-off
      AdoCbl and PrCbl with competition between rapid nonradiative decay leading to
      ground state recovery and formation of a radical pair following bond homolysis.

PMID- 20815361
TI  - Progress toward the total synthesis of (+/-)-havellockate.
AB  - Havellockate (1) was isolated from the soft coral Sinularia granosa located on
      the Havellock island in the Indian Ocean. This highly compact and polyoxygenated
      marine diterpene bears a cis-fused hydrindane core that contains eight
      stereogenic centers as well as a spiro-lactone. To the best of our knowledge, no
      syntheses of 1 have been reported yet. Herein, we describe the synthesis of the
      all-carbon framework of havellockate (1) in 18 chemical operations. Our approach
      highlights the efficiency and utility of the hydroxy-directed Diels-Alder (HDDA)
      reaction to quickly access the cis-fused hydrindane core and securing the correct
      stereochemistry at C6 and C7. Moreover, six of the eight stereogenic centers have
      been installed in the correct stereochemistry.

PMID- 20815362
TI  - Mixed-valence dinitrogen-bridged Fe(0)/Fe(II) complex.
AB  - The reactions of a dinitrogen-bridged Fe(II)/Fe(II) complex [(FeH(PP(3)))(2)(MU
      N(2))](2+) (3) (PP(3) = P(CH(2)CH(2)PMe(2))(3)) with base were investigated using
      (15)N labeling techniques to enhance characterization. In the presence of base, 3
      is initially deprotonated to the Fe(II)/Fe(0) dinitrogen-bridged complex
      [(FeH(PP(3)))(MU-N(2))(Fe(PP(3)))](+) (4) and then to the symmetrical Fe(0)/Fe(0)
      dinitrogen-bridged complex (Fe(PP(3)))(2)(MU-N(2)) (5). [(FeH(PP(3)))(MU
      N(2))(Fe(PP(3)))](+) (4) exhibits unusual long-range (31)P-(31)P NMR coupling
      through the bridging dinitrogen ligand from the phosphines at the Fe(0) center
      and those at the Fe(II) center. Reaction of 4 with base under an atmosphere of
      argon resulted in the known dinitrogen Fe(0) complex Fe(N(2))(PP(3)) (6) and a
      solvent C-H activation product. Complexes 3, 4, and 5 were fully characterized by
      multinuclear NMR spectroscopy, and complexes 3 and 4 by X-ray crystallography.

PMID- 20815364
TI  - Patterning of self-assembled pentacene nanolayers by extreme ultraviolet-induced
      three-dimensional polymerization.
AB  - Most researchers expect extreme ultraviolet lithography (EUVL) to be used to
      create patterns below 32 nm in semiconductor devices. An ultrathin EUV
      photoresist (PR) layer a few nanometers thick is required to further reduce the
      minimum feature size. Here, we show for the first time that pentacene molecular
      layers can be employed as a new EUV resist. Nanometer-scale dots and lines have
      been successfully realized using the new molecular resist. We clearly show the
      mechanism that forms the nanopatterns using a scanning photoemission microscope,
      EUV interference lithography, an atomic force microscope, and photoemission
      spectroscopy. The molecular PR has several advantages over traditional polymer
      EUV PRs. For example, it has high thermal/chemical stability, negligible
      outgassing, the ability to control the height and width on the nanometer scale,
      fewer residuals, no need for a chemical development process and thus a reduction
      of chemical waste when making nanopatterns. Besides, it can be applied to any
      substrate to which pentacene bonds chemically, such as SiO2, SiN, and SiON, which
      are important films in the semiconductor device industry.

PMID- 20815363
TI  - Structures of cytochrome P450 2B4 complexed with the antiplatelet drugs
      ticlopidine and clopidogrel .
AB  - Prior X-ray crystal structures of rabbit cytochrome P450 2B4 (2B4) in complexes
      with various imidazoles have demonstrated markedly different enzyme conformations
      depending on the size of the inhibitor occupying the active site. In this study,
      structures of 2B4 were determined with the antiplatelet drugs clopidogrel and
      ticlopidine, which were expected to have greater freedom of movement in the
      binding pocket. Ticlopidine could be modeled into the electron density maps in
      two distinct orientations, both of which are consistent with metabolic data
      gathered with other mammalian P450 enzymes. Results of ligand docking and heme
      induced NMR relaxation of drug protons showed that ticlopidine was preferentially
      oriented with the chlorophenyl group closest to the heme. Because of its
      stereocenter, clopidogrel was easier to fit in the electron density and exhibited
      a single orientation, which points the chlorophenyl ring toward the heme. The
      C(alpha) traces of both complexes aligned very well with each other and revealed
      a compact, closed structure that resembles the conformation observed in two
      previously determined 2B4 structures with the small molecule inhibitors 4-(4
      chlorophenyl)imidazole and 1-(4-chlorophenyl)imidazole. The 2B4 active site is
      able to accommodate small ligands by moving only a small number of side chains,
      suggesting that ligand reorientation is energetically favored over protein
      conformational changes for binding of these similarly sized molecules. Adjusting
      both protein conformation and ligand orientation in the active site gives 2B4 the
      flexibility to bind to the widest range of molecules, while also being
      energetically favorable.

PMID- 20815365
TI  - Structural characterization and antimicrobial activity of the Zn(II) complex with
      P113 (demegen), a derivative of histatin 5.
AB  - Zinc binding to P113 (or demegen), a 12 amino acid (AKRHHGYKRKFH-NH(2)) fragment
      of histatin 5, was investigated by means of NMR and CD techniques, yielding
      delineation of the metal binding site and the 3D structure of the complex in
      water and in DMSO as well. The three His imidazole and the N-terminus nitrogens
      were found to act as the zinc coordinating atoms. A comparison with the
      previously reported Cu(II)-P113 complex disclosed that the two structures were
      rather diverse, in spite of an identical donor set. The two complexes were also
      tested for their antimicrobial activity in vitro against seven bacteria and two
      yeast strains: a minor activity of both complexes vs that of free ligand was
      given evidence, suggesting both metal ions may possibly play a negative role in
      vivo.

PMID- 20815366
TI  - Anthraquinone, cyclopentanone, and naphthoquinone derivatives from the sea fan
      derived fungi Fusarium spp. PSU-F14 and PSU-F135.
AB  - Five new metabolites, fusaranthraquinone (1), fusarnaphthoquinones A-C (2-4), and
      fusarone (5), were isolated from the sea fan-derived fungi Fusarium spp. PSU-F14
      and PSU-F135 along with 18 known compounds. The structures were elucidated on the
      basis of spectroscopic evidence. Their antibacterial, antifungal,
      antimycobacterial, antimalarial, and cytotoxic activities were examined.

PMID- 20815367
TI  - Second-sphere tethering of rare-earth ions to cucurbit[6]uril by iminodiacetic
      acid involving carboxylic group encapsulation.
AB  - The reaction of rare-earth nitrates with iminodiacetic acid (H(2)IDA) in the
      presence of cucurbit[6]uril (CB6) in water at room temperature yields a family of
      isomorphous complexes, [M(H(2)IDA)(NO(3))(H(2)O)(6)](NO(3))(2).CB6.14H(2)O with M
      = Y (1), Ce (2), Nd (3), Eu (4), Dy (5), Er (6), Tm (7), and Yb (8). In these
      compounds, the trivalent metal ion is bound to one nitrate ion, six water
      molecules, and one zwitterionic H(2)IDA molecule. The latter is further partly
      included in the CB6 cavity, with the ammonium group forming two hydrogen bonds
      with oxygen atoms of one portal. The uncoordinated carboxylic group is thus
      encapsulated in CB6 and hydrogen-bonded to the other portal via a water molecule.
      CB6 is a second-sphere ligand in these complexes, but direct bonding of the metal
      ion to CB6 can be enforced by using a ligand more deeply imbedded in the cavity,
      such as 2-pyridylacetate (PA) in [Eu(PA)(CB6)(NO(3))(H(2)O)(5)](NO(3)).10H(2)O
      (11). When the reaction with H(2)IDA is performed with Lu(III) or Cu(II), no
      metal complex is isolated, but the inclusion compounds
      [(H(3)IDA)(2)(CB6)](NO(3))(2).xH(2)O with x = 6 (9) or 8 (10) are obtained
      instead, in which the two H(3)IDA(+) cations are attached to the CB6 portals by
      ammonium-carbonyl hydrogen bonds and are linked to one another inside the cavity
      by hydrogen bonding between the carboxylic groups. These complexes are compared
      to that comprising a dicarboxylic acid devoid of an ammonium functionality,
      [(H(2)AZ)(CB6)].6H(2)O (12), where H(2)AZ is azelaic acid. The metal ion
      complexes 1-8 and the organic complexes 9 and 10 display the unprecedented
      feature of inclusion of carboxylic groups inside the CB6 cavity, with the
      CB6/acid stoichiometry and the finer details of the host-guest interactions being
      dependent on the presence of the metal ion.

PMID- 20815368
TI  - Efficient preparation of large-area graphene oxide sheets for transparent
      conductive films.
AB  - Large-area sheets are highly desirable for fundamental research and technological
      applications of graphene. Here we introduce a modified chemical exfoliation
      technique to prepare large-area graphene oxide (GO) sheets. The maximum area of
      the GO sheets obtained can reach ~40000 MUm(2). We found that the GO area is
      strongly correlated with the C-O content of the graphite oxide, which enables the
      area of the synthesized GO sheets to be controlled. By simply changing oxidation
      conditions, GO sheets with an average area of ca. 100-300, ca. 1000-3000, and
      ~7000 MUm(2) were selectively synthesized. For transparent conductive film
      applications, thin GO films were fabricated by self-assembly on a liquid/air
      interface and reduced by HI acid. We found that the sheet resistance of the
      reduced GO (rGO) films decreases with increasing sheet area at the same
      transmittance because of the decrease in the number of intersheet tunneling
      barriers. The rGO film made from GO sheets with an average area of ~7000 MUm(2)
      shows a sheet resistance of 840 Omega/sq at 78% transmittance, which is much
      lower than that (19.1 kOmega/sq at 79% transmittance) of a rGO film made from
      small-area GO sheets of ca. 100-300 MUm(2), and comparable to that of graphene
      films grown on Ni by chemical vapor deposition.

PMID- 20815371
TI  - Molecular-scale change in the surface properties of silica and copper in pure
      water with time.
AB  - We aimed to understand one of the fundamentals of how silica and copper surfaces
      are flattened on the molecular scale by the chemical mechanical polishing (CMP)
      method, which is used in the fabrication of semiconductors. In particular, we
      examined whether even pure water affects the properties of silica and copper
      surfaces. This study used the atomic force microscope to detect how the
      morphologies, normal interaction, and friction forces of the silica and copper
      surfaces changed with their exposure time to water. We found that the surface
      properties of even the silica surfaces changed on the molecular scale when the
      surfaces were exposed to water for a sufficiently long time. In the case of
      copper, the surface properties were observed to undergo rapid changes. Gel-like
      layers were detected on the copper surface within a few minutes, even though
      copper surfaces oxidized by ambient air are considered to be rather stable to
      water.

PMID- 20815370
TI  - Lactone pathway to statins utilizing the Wittig reaction. The synthesis of
      rosuvastatin.
AB  - The first entry to statins via lactonized side chain is reported, exemplified by
      the synthesis of rosuvastatin. The key step is Wittig coupling of (2S,4R)-4-(tert
      butyldimethylsilyloxy)-6-oxotetrahydro-2H-pyran-2-carbaldehyde and phosphonium
      salt of an appropriately functionalized pyrimidine heterocycle. One-pot
      deprotection and hydrolysis of the resulting 4-O-TBS rosuvastatin lactone
      provided rosuvastatin in high yield.

PMID- 20815369
TI  - Intramolecular heme ligation of the cytochrome P450 2C9 R108H mutant demonstrates
      pronounced conformational flexibility of the B-C loop region: implications for
      substrate binding.
AB  - A previous study [Dickmann, L., et al. (2004) Mol. Pharmacol. 65, 842-850]
      revealed some unusual properties of the R108H mutant of cytochrome P450 2C9
      (CYP2C9), including elevated thermostability relative to that of CYP2C9, as well
      as a UV-visible absorbance spectrum that was indicative of nitrogenous ligation
      to the heme iron. In our study, size-exclusion chromatography and UV-visible
      absorbance spectroscopy of CYP2C9 R108H monomers demonstrated that nitrogen
      ligation is indeed intramolecular. Pulsed electron paramagnetic resonance of
      CYP2C9 R108H monomers showed that a histidine is most likely bound to the heme as
      previously hypothesized. An energy-minimized model of the R108H mutant maintained
      a CYP fold, despite substantial movement of several loop regions of the mutant,
      and, therefore, represents an extreme example of a closed conformation of the
      enzyme. Molecular dynamics (MD) simulations of CYP2C9 were performed to study the
      range of energetically accessible CYP2C9 conformations. These in silico studies
      showed that the B-C loop region of CYP2C9 moves away from the heme to a position
      resembling the putative open conformation described for rabbit CYP2B4. A model
      involving the movement of the B-C loop region and R108 between the open and
      closed conformations of CYP2C9 is presented, which helps to explain the enzyme's
      ability to regio- and stereospecifically metabolize some ligands while
      allosterically activating others.

PMID- 20815372
TI  - Enantioselective and protecting group-free synthesis of 1-deoxythionojirimycin, 1
      deoxythiomannojirimycin, and 1-deoxythiotalonojirimycin.
AB  - 1-Deoxythioglyconojirimycins were synthesized by using a protecting group-free
      strategy, starting from readily available carbohydrates, in good overall yield.
      Use of benzyltriethylammonium tetrathiomolybdate, [BnEt(3)N](2)MoS(4), as a
      sulfur transfer reagent and borohydride exchange resin (BER) reduction of a
      lactone enabled the efficient synthesis of the title compounds.

PMID- 20815373
TI  - Palladium-catalyzed cross-coupling of cyclopropylmagnesium bromide with aryl
      bromides mediated by zinc halide additives.
AB  - The key Pd-catalyzed cross-coupling of aryl bromides or triflates and
      cyclopropylmagnesium bromide in the presence of substoichiometric amounts of zinc
      bromide produces cyclopropyl arenes in good to excellent yields. The cross
      coupling of other alkyl, cycloalkyl, and aryl Grignard reagents with aryl
      bromides under the same conditions gives the corresponding substituted arenes in
      good yields.

PMID- 20815374
TI  - Enhanced photoassisted water electrolysis using vertically oriented anodically
      fabricated Ti-Nb-Zr-O mixed oxide nanotube arrays.
AB  - Self-ordered, highly oriented arrays of titanium-niobium-zirconium mixed oxide
      nanotube films were fabricated by the anodization of Ti(35)Nb(5)Zr alloy in
      aqueous and formamide electrolytes containing NH(4)F at room temperature. The
      nanostructure topology was found to depend on the nature of the electrolyte and
      the applied voltage. Our results demonstrate the possibility to grow mixed oxide
      nanotube array films possessing several-micrometer-thick layers by a simple and
      straightforward electrochemical route. The fabricated Ti-Nb-Zr-O nanotubes showed
      a ~17.5% increase in the photoelectrochemical water oxidation efficiency as
      compared to that measured for pure TiO(2) nanotubes under UV illumination (100
      mW/cm(2), 320-400 nm, 1 M KOH). This enhancement could be related to a
      combination of the effect of the thin wall of the fabricated Ti-Nb-Zr-O nanotubes
      (10 +/- 2 nm) and the formation of Zr oxide and Nb oxide layers on the nanotube
      surface, which seems to slow down the electron-hole recombination in a way
      similar to that reported for Gratzel solar cells.

PMID- 20815375
TI  - Very contracted to extended co-conformations with or without oscillations in two-
      and three-station [c2]daisy chains.
AB  - The syntheses of various two- and three-station mannosyl [c2]daisy chains, based
      on a dibenzo-24-crown-8 macrocyclic moiety and an ammonium, a triazolium, and a
      mono- or disubstituted pyridinium amide station, are reported. The ability of
      these molecules to act as molecular machine based mimetics has been further
      studied by (1)H NMR studies. In all the protonated ammonium states, the
      interwoven rotaxane dimers adopt an extended co-conformation. However,
      carbamoylation of the ammonium station led to many different other [c2]daisy
      chain co-conformations, depending on the other molecular stations belonging to
      the axle. In the two-station [c2]daisy chains containing an ammonium and a mono-
      or disubstituted pyridinium amide station, two large-amplitude relative movements
      of the interwoven components were noticed and afforded either an extended and a
      contracted or very contracted state with, in the latter case, an impressive
      chairlike conformational flipping of the mannopyranose from (1)C(4) to (4)C(1).
      In the case of the three-station-based [c2]daisy chains containing an ammonium, a
      triazolium, and disubstituted pyridinium amide, an extended and a half-contracted
      molecular state could be obtained because of the stronger affinity of the dibenzo
      24-crown-8 part for, respectively, the ammonium, the triazolium, and the
      disubstituted pyridinium amide. Eventually, with axles comprising an ammonium, a
      triazolium, and a monosubstituted pyridinium amide, an extended conformation was
      noticed in the protonated state whereas a continuous oscillation between half
      contracted and contracted states, in fast-exchange on the NMR time scale, was
      triggered by carbamoylation. Variations of the solvent or the temperature allow
      the modification of the population of each co-conformer. Thermodynamic data
      provided a small free Gibbs energy DeltaG of 2.1 kJ.mol(-1) between the two
      translational isomers at 298 K.

PMID- 20815376
TI  - Primary tumor xenografts of human lung adeno and squamous cell carcinoma express
      distinct proteomic signatures.
AB  - Nonsmall cell lung carcinoma (NSCLC) accounts for 80% of lung cancers. The most
      prevalent subtypes of NSCLC are adenocarcinoma (ADC) and squamous cell carcinoma
      (SCC), which combined account for approximately 90%. Ten resected NSCLC patient
      tumors (5 ADC and 5 SCC) were directly introduced into severely immune deficient
      (NOD-SCID) mice, and the resulting xenograft tumors were analyzed by standard
      histology and immunohistochemistry (IHC) and by proteomics profiling. Mass
      spectrometry (MS) methods involving 1- and 2-dimensional LC-MS/MS, and
      multiplexed selective reaction monitoring (SRM, or MRM), were applied to identify
      and quantify the xenograft proteomes. Hierarchical clustering of protein profiles
      distinguished between the ADC and SCC subtypes. The differential expression of
      178 proteins, including a comprehensive panel of intermediate filament keratin
      proteins, was found to constitute a distinctive proteomic signature associated
      with the NSCLC subtypes. Epidermal growth factor receptor (EGFR) was expressed in
      ADC and SCC xenografts, and EGFR network activation was assessed by
      phosphotyrosine profiling by Western blot analysis and SRM measurement of EGFR
      levels, and mutation analysis. A multiplexed SRM/MRM method provided relative
      quantification of several keratin proteins, EGFR and plakophilin-1 in single LC
      MS/MS runs. The protein quantifications by SRM and MS/MS spectral counting were
      associated with superior dynamic range and reproducibility but were otherwise
      consistent with orthogonal methods including IHC and Western immuno blotting.
      These findings illustrate the potential to develop a comprehensive MS-based
      platform in oncologic pathology for better classification and potentially
      treatment of NSCLC patients.

PMID- 20815377
TI  - Molecular details of the yeast frataxin-Isu1 interaction during mitochondrial Fe
      S cluster assembly.
AB  - Frataxin, a conserved nuclear-encoded mitochondrial protein, plays a direct role
      in iron-sulfur cluster biosynthesis within the ISC assembly pathway. Humans with
      frataxin deficiency have Friedreich's ataxia, a neurodegenerative disorder
      characterized by mitochondrial iron overload and disruption in Fe-S cluster
      synthesis. Biochemical and genetic studies have shown frataxin interacts with the
      iron-sulfur cluster assembly scaffold protein (in yeast, there are two, Isu1 and
      Isu2), indicating frataxin plays a direct role in cluster assembly, possibly by
      serving as an iron chaperone in the assembly pathway. Here we provide molecular
      details of how yeast frataxin (Yfh1) interacts with Isu1 as a structural module
      to improve our understanding of the multiprotein complex assembly that completes
      Fe-S cluster assembly; this complex also includes the cysteine desulfurase (Nfs1
      in yeast) and the accessory protein (Isd11), together in the mitochondria.
      Thermodynamic binding parameters for protein partner and iron binding were
      measured for the yeast orthologs using isothermal titration calorimetry. Nuclear
      magnetic resonance spectroscopy was used to provide the molecular details to
      understand how Yfh1 interacts with Isu1. X-ray absorption studies were used to
      electronically and structurally characterize how iron is transferred to Isu1 and
      then incorporated into an Fe-S cluster. These results were combined with
      previously published data to generate a structural model for how the Fe-S cluster
      protein assembly complex can come together to accomplish Fe-S cluster assembly.

PMID- 20815378
TI  - Sequential aeration of membrane-aerated biofilm reactors for high-rate
      autotrophic nitrogen removal: experimental demonstration.
AB  - One-stage autotrophic nitrogen (N) removal, requiring the simultaneous activity
      of aerobic and anaerobic ammonium oxidizing bacteria (AOB and AnAOB), can be
      obtained in spatially redox-stratified biofilms. However, previous experience
      with Membrane-Aerated Biofilm Reactors (MABRs) has revealed a difficulty in
      reducing the abundance and activity of nitrite oxidizing bacteria (NOB), which
      drastically lowers process efficiency. Here we show how sequential aeration is an
      effective strategy to attain autotrophic N removal in MABRs: Two separate MABRs,
      which displayed limited or no N removal under continuous aeration, could remove
      more than 5.5 g N/m(2)/day (at loads up to 8 g N/m(2)/day) by controlled
      variation of sequential aeration regimes. Daily averaged ratios of the surficial
      loads of O(2) (oxygen) to NH(4)(+) (ammonium) (L(O(2))/L(NH(4))) were close to
      1.73 at this optimum. Real-time quantitative PCR based on 16S rRNA gene confirmed
      that sequential aeration, even at elevated average O(2) loads, stimulated the
      abundance of AnAOB and AOB and prevented the increase in NOB. Nitrous oxide
      (N(2)O) emissions were 100-fold lower compared to other anaerobic ammonium
      oxidation (Anammox)-nitritation systems. Hence, by applying periodic aeration to
      MABRs, one-stage autotrophic N removal biofilm reactors can be easily obtained,
      displaying very competitive removal rates, and negligible N(2)O emissions.

PMID- 20815379
TI  - Dioxins: an overview and history.

PMID- 20815380
TI  - Environmental persistence of a highly pathogenic avian influenza (H5N1) virus.
AB  - Human cases of disease caused by highly pathogenic avian influenza (HPAI) viruses
      of the H5N1 subtype are rare, yet characterized with a mortality rate of
      approximately 60%. Tests were conducted to determine the environmental
      persistence of an HPAI (H5N1) virus on four materials (glass, wood, galvanized
      metal, and topsoil) that could act as fomites or harbor the virus. Test coupons
      were inoculated with the virus and exposed to one of five environmental
      conditions that included changes in temperature, relative humidity, and simulated
      sunlight. At time periods up to 13 days, the virus was extracted from each
      coupon, and quantified via cytopathic effects on Madin-Darby canine kidney cells.
      The virus was most persistent under the low temperature condition, with less than
      1 log reduction on glass and steel after 13 days at low relative humidity. Thus,
      at these conditions, the virus would be expected to persist appreciably beyond 13
      days.

PMID- 20815381
TI  - Chemical synthesis of fully biomass-based poly(butylene succinate) from inedible
      biomass-based furfural and evaluation of its biomass carbon ratio.
AB  - We have produced fully biomass-based poly(butylene succinate) (PBS) from furfural
      produced from inedible agricultural cellulosic waste. Furfural was oxidized to
      give fumaric acid. Fumaric acid was hydrogenated under high pressure with a
      palladium-rhenium/carbon catalyst to give 1,4-butanediol, and with a
      palladium/carbon catalyst to give succinic acid. Dimethyl succinate was
      synthesized from fumaric acid by esterification and hydrogenation under normal
      pressure. Fully biomass-based PBS was obtained by polycondensation of biomass
      based 1,4-butanediol and biomass-based succinic acid or dimethyl succinate. The
      biomass carbon ratio calculated from (14)C concentrations measured by accelerator
      mass spectroscopy (AMS) verified that the PBS obtained in this study contained
      only biomass carbon. The polycondensation of biomass-based 1,4-butanediol and
      petroleum-based terephthalic acid or dimethyl terephthalate gave partially
      biomass-based poly(butylene terephthalate), which is an engineering plastic.

PMID- 20815382
TI  - Structure and dynamics of [3.3]paracyclophane as studied by nuclear magnetic
      resonance and density functional theory calculations.
AB  - Strained cyclophanes with small (-CH(2)-)(n) bridges connecting two benzene rings
      are interesting objects of basic research, mostly because of the nonplanarity of
      the rings and of interference of pi-electrons of the latter. For title
      [3.3]paracyclophane, in solutions occurring in two interconverting cis and trans
      conformers, the published nuclear magnetic resonance (NMR) data are incomplete
      and involve its partially deuterated isotopomers. In this paper, variable
      temperature NMR studies of its perprotio isotopomer combined with DFT quantum
      chemical calculations provide a complete characterization of the solution
      structure, NMR parameters, and interconversion of the cis and trans isomers of
      the title compound. Using advanced methods of spectral analysis, total
      quantitative interpretation of its proton NMR spectra in both the static and
      dynamic regimes is conducted. In particular, not only the geminal but also all of
      the vicinal J(HH) values for the bridge protons are determined, and for the first
      time, complete Arrhenius data for the interconversion process are reported. The
      experimental proton and carbon chemical shifts and the (n)J(HH), (1)J(CH), and
      (1)J(CC) coupling constants are satisfactorily reproduced theoretically by the
      values obtained from the density functional theory calculations.

PMID- 20815383
TI  - NMR crystallography of campho[2,3-c]pyrazole (Z' = 6): combining high-resolution
      1H-13C solid-state MAS NMR spectroscopy and GIPAW chemical-shift calculations.
AB  - (1)H-(13)C two-dimensional magic-angle spinning (MAS) solid-state NMR correlation
      spectra, recorded with the MAS-J-HMQC experiment, are presented for campho[2,3
      c]pyrazole. For each (13)C moiety, there are six resonances associated with the
      six distinct molecules in the asymmetric unit cell (Z' = 6). The one-bond C-H
      correlations observed in the 2D (1)H-(13)C MAS-J-HMQC spectra allow the
      experimental determination of the (1)H and (13)C chemical shifts associated with
      the separate CH, CH(2), and CH(3) groups. (1)H and (13)C chemical shifts
      calculated by using the GIPAW (Gauge Including Projector Augmented Waves) plane
      wave pseudopotential approach are presented. Calculations for the whole unit cell
      (12 * 29 = 348 atoms, with geometry optimization of all atoms) allow the
      assignment of the experimental (1)H and (13)C chemical shifts to the six distinct
      molecules. The calculated chemical shifts for the full crystal structure are
      compared with those for isolated molecules as extracted from the geometry
      optimized crystal structure. In this way, the effect of intermolecular
      interactions on the observed chemical shifts is quantified. In particular, the
      calculations are sufficiently precise to differentiate the small (<1 ppm)
      differences between the (1)H chemical shifts of the six resonances associated
      with each distinct CH or CH(2) moiety.

PMID- 20815384
TI  - Mechanism of racemization of chiral alcohols mediated by 16-electron ruthenium
      complexes.
AB  - Experimental and computational analyses provide support for the existence of a
      metal-hydride-based mechanism for the ruthenium-mediated racemization of chiral
      alcohols.

PMID- 20815385
TI  - Cyano Diels-Alder and cyano ene reactions. Applications in a formal [2 + 2 + 2]
      cycloaddition strategy for the synthesis of pyridines.
AB  - Two metal-free, formal [2 + 2 + 2] cycloaddition strategies for the construction
      of polycyclic pyridine derivatives are described that proceed via pericyclic
      cascade mechanisms featuring the participation of unactivated cyano groups as
      enophile and dienophile cycloaddition partners.

PMID- 20815386
TI  - Relating n-pentane isomerization activity to the tungsten surface density of
      WO(x)/ZrO2.
AB  - Zirconia-supported tungsten oxide (WO(x)/ZrO(2)) is considered an important
      supported metal oxide model acid catalyst, for which structure-property
      relationships have been studied for numerous acid-catalyzed reactions. The
      catalytic activity for xylene isomerization, alcohol dehydration, and aromatic
      acylation follows a volcano-shape dependence on tungsten surface density.
      However, WO(x)/ZrO(2) has not been studied for more acid-demanding reactions,
      like n-pentane isomerization, with regard to surface density dependence. In this
      work, WO(x)/ZrO(2) was synthesized using commercially available amorphous
      ZrO(x)(OH)(4-2x) and model crystalline ZrO(2) as support precursors. They were
      analyzed for n-pentane isomerization activity and selectivity as a function of
      tungsten surface density, catalyst support type, and calcination temperature.
      Amorphous ZrO(x)(OH)(4-2x) led to WO(x)/ZrO(2) (WZrOH) that exhibited maximum
      isomerization activity at ~5.2 W.nm(-2), and the crystalline ZrO(2) led to a
      material (WZrO(2)) nearly inactive at all surface densities. Increasing the
      calcination temperature from 773 to 973 K increased the formation of 0.8-1 nm Zr
      WO(x) clusters detected through direct imaging on an aberration-corrected high
      resolution scanning transmission electron microscope (STEM). Calcination
      temperature further increased catalytic activity by at least two times. Bronsted
      acidity was not affected but Lewis acidity decreased in number, as quantified via
      pyridine adsorption infrared spectroscopy. WO(x)/ZrO(2) exhibited isomerization
      activity that peaked within the first 2 h time-on-stream, which may be due to Zr
      WO(x) clusters undergoing an activation process.

PMID- 20815388
TI  - Noncationic dipeptide mimic oligomers as cell penetrating nonpeptides (CPNP).
AB  - Small oligomers of constrained dipeptide mimics have been synthesized as new
      vectors for intracellular delivery. They are highly internalized by cells and
      delivered to the lysosomes by an energy-dependent pathway. This new class of
      vectors referred to as cell penetrating nonpeptides (CPNP) possess the
      distinctive feature of being noncationic.

PMID- 20815389
TI  - Evaluating the potential of native ureolytic microbes to remediate a 90Sr
      contaminated environment.
AB  - This study was a preliminary evaluation of ureolytically driven calcite
      precipitation and strontium coprecipitation for remediating (90)Sr contamination
      at the Hanford 100-N Area in Washington; in particular the approach is suitable
      for treating sorbed (90)Sr that could otherwise be a long-term source for
      groundwater contamination. Geochemical conditions at the site are compatible with
      long-term calcite stability, and therefore groundwater and sediment samples were
      examined to assess the ureolytic capabilities of the native microbiota.
      Quantitative assays detected up to 2 * 10(4) putative ureC gene copies mL(-1) in
      water and up to 9 * 10(5) copies g(-1) in sediment. The ureC assays and
      laboratory-based estimates of ureolytic activity indicated that the distribution
      of in situ ureolytic potential was very heterogeneous with depth and also that
      the ureolytic activity was predominantly associated with attached organisms. A
      mixed kinetic-equilibrium model was developed for the 100-N site to simulate urea
      treatment and predict strontium removal. Together, the microbial characterization
      data and modeling suggest that the site has the requisite biogeochemical
      characteristics for application of the calcite precipitation remediation approach
      for (90)Sr.

PMID- 20815390
TI  - Structures of metallosupramolecular coordination assemblies can be obtained by
      ion mobility spectrometry-mass spectrometry.
AB  - Rigid rectangular, triangular, and prismatic supramolecular assemblies,
      cyclobis[(2,9-bis[trans-Pt(PEt(3))(2)(PF(6))]anthracene)(4,4'-dipyridyl)],
      cyclotris[(2,9-bis[trans-Pt(PEt(3))(2)(PF(6))]phenanthrene)(4,4'-dipyridyl)], and
      cyclotris[bis[cis-Pt(PEt(3))(2)(CF(3)SO(3))(2)]tetrakis(4
      pyridyl)cyclobutadienecyclopentadienylcobalt(I)], respectively, based on
      dipyridyl ligands and square planar platinum coordination, have been investigated
      by ion mobility spectrometry-mass spectrometry (IMS-MS). Electrospray ionization
      quadrupole and time-of-flight spectra have been obtained and fragmentation
      pathways assigned. Ion mobility studies give cross sections that compare very
      well with cross sections of the supramolecular rectangle and triangle species on
      the basis of X-ray bond distances. For the larger prism structures, agreement of
      experimental and calculated cross sections from molecular modeling is very good,
      indicating IMS-MS methods can be used to characterize complex self-assembled
      structures where X-ray or other spectroscopic structures are not available.

PMID- 20815391
TI  - Potentials of mean force and permeabilities for carbon dioxide, ammonia, and
      water flux across a Rhesus protein channel and lipid membranes.
AB  - As a member of the ubiquitous ammonium transporter/methylamine permease/Rhesus
      (Amt/MEP/Rh) family of membrane protein channels, the 50 kDa Rhesus channel
      (Rh50) has been implicated in ammonia (NH(3)) and, more recently, also in carbon
      dioxide (CO(2)) transport. Here we present molecular dynamics simulations of
      spontaneous full permeation events of ammonia and carbon dioxide across Rh50 from
      Nitrosomonas europaea. The simulations show that Rh50 is functional in its
      crystallographic conformation, without the requirement for a major conformational
      change or the action of a protein partner. To assess the physiological relevance
      of NH(3) and CO(2) permeation across Rh50, we have computed potentials of mean
      force (PMFs) and permeabilities for NH(3) and CO(2) flux across Rh50 and compare
      them to permeation through a wide range of lipid membranes, either composed of
      pure lipids or composed of lipids plus an increasing cholesterol content.
      According to the PMFs, Rh50 is expected to enhance NH(3) flux across dense
      membranes, such as membranes with a substantial cholesterol content. Although
      cholesterol reduces the intrinsic CO(2) permeability of lipid membranes, the
      CO(2) permeabilities of all membranes studied here are too high to allow
      significant Rh50-mediated CO(2) flux. The increased barrier in the PMF for water
      permeation across Rh50 shows that Rh50 discriminates 40-fold between water and
      NH(3). Thus, Rh50 channels complement aquaporins, allowing the cell to regulate
      water and NH(3) flux independently. The PMFs for methylamine and NH(3) are
      virtually identical, suggesting that methylamine provides an excellent model for
      NH(3) in functional experiments.

PMID- 20815392
TI  - Exploration of organic acid chain length on water-soluble silicon quantum dot
      surfaces.
AB  - Surface functionalization of silicon quantum dots influences oxidation of the
      silicon core while affording control of physical properties and maintaining
      optical stability. An effective method for surface modification is photochemical
      hydrosilylation in which the hydride-terminated Si surface is reacted with an
      unsaturated C-C bond resulting in a covalent Si-C bond at the surface. The
      physical properties (e.g., reactivity and solvent compatibility) of the
      nanocrystals are thus dictated by those of the pendant functional group. Water
      soluble nanoparticles can be produced by extending polar functional groups, such
      as carboxylic acids, from the surface. Previous literature reports have shown
      acrylic acid to be an attractive starting material for creating water-soluble Si
      nanocrystals. To date, a detailed study of the effects of differing surface
      groups (i.e., carboxylic acids of varying carbon chain lengths) has not been
      offered. Here, we investigate the effects of carboxylic acid surface moieties
      with increasing carbon chain length on various silicon nanocrystal properties.
      Oxidative and optical stability was improved by increasing the length of the
      carbon spacer between the silicon surface and the polar carboxylic acid group. As
      well, increased chain length was found to enhance nanocrystal dispersibility in
      polar solvents. Of important note, however, the use of acrylic acid as a
      precursor led to poly(acrylic acid) formation under the reaction conditions
      studied, leading to anomalous behavior compared to precursors with longer carbon
      chains.

PMID- 20815393
TI  - Synthesis, structure, and reactivity of N-benzoyl iminophosphoranes ortho
      lithiated at the benzoyl group.
AB  - Ortho lithiation of N-benzamido-P,P,P-triaryliminophosphoranes through
      deprotonation with alkyllithium bases was achieved with ortho-C?O and ortho-P?N
      chemoselectivity. However, the synthetic scope of these processes was rather
      limited. Ortho-lithiated N-benzamido-P,P,P-triphenyliminophosphorane 8 was
      efficiently prepared via lithium/halogen exchange of the corresponding ortho
      brominated precursor with s-BuLi in THF at -90  degrees C. The reaction of 8 with
      a variety of electrophiles provides an easy and mild method for the
      regioselective synthesis of ortho-modified iminophosphoranes via C-C (alkylation
      and hydroxyalkylation) and C-X (X = I, Si, P, Sn, and Hg) bond-forming reactions.
      NMR characterization of 8 in THF solution showed that 8 exists as an equilibrium
      mixture of one monomer and two dimers. The Li atoms of these species become
      members of five-membered rings through chelation by the ortho-metalated carbon
      and the carbonyl oxygen. The dimers differ in the relative orientation of the two
      chelates with respect to the plane defined by the C(2)Li(2) core. The equilibrium
      between all species is established by splitting the dimers into monomers and
      subsequent recombination with formation of a different dimer.

PMID- 20815394
TI  - Noninjection gram-scale synthesis of monodisperse pyramidal CuInS2 nanocrystals
      and their size-dependent properties.
AB  - CuInS2 nanocrystals are viewed as very good candidates for solar harvesting and
      light emitting applications. Here we report an optimized noninjection method for
      the synthesis of monodisperse pyramidal CuInS2 nanocrystals with sizes ranging
      from 3 to 8 nm. This synthetic route is able to yield large amounts of high
      quality nanoparticles, usually in the gram scale for one batch experiment. The
      structure and surface studies showed that the resulting nanocrystals are pyramids
      of CuInS2 tetragonal phase with well-defined facets, while their surface is
      functionalized with dodecanethiol capping ligands. Spectroscopic and
      electrochemical measurements revealed size-dependent optical and electrical
      properties of CuInS2 nanocrystals, demonstrating quantum confinement effects in
      these systems. The size-dependent optical bandgaps of CuInS2 nanocrystals were
      found to be consistent with the finite-depth well effective mass approximation
      (EMA) calculations, which provide a convenient method to estimate the diameter of
      CuInS2 pyramids. Additionally we have also determined some important physical
      parameters, including bandgaps and energy levels, for this system, which are
      crucial for the integration of CuInS2 nanocrystals in potential device
      applications.

PMID- 20815395
TI  - Reactivity of anhydrous keggin-type heteropolyacids with alkylsilanes: synthesis
      and characterization.
AB  - Anhydrous tungstic heteropolyacids react with alkylsilanes in the absence of
      solvent, leading to the evolution of hydrogen and the formation of a new kind of
      species where silicon is only weakly interacting with the polyoxometalate. The
      resulting material was characterized by various physicochemical methods including
      NMR, IR, and Raman spectroscopy. The most interesting feature is the unusual
      chemical shift of the (29)Si nuclei (ca. +50 ppm), which confirms the formation
      of a quasi-ionic bond between the organic and inorganic moieties. The weakness of
      this bond was also evidenced by chemical reactivity with nBu(4)NCl (leading to
      the formation of R(3)SiCl species) and oxygen. This new kind of structure can be
      of great interest in the field of microelectronics. Indeed the reactivity
      described in this article can be used and transferred easily in heterogeneous
      conditions to introduce defects in semiconductors.

PMID- 20815396
TI  - Biosynthesis and characterization of organosoluble conjugated poly(2
      aminofluorene) with the pyrazine bridged.
AB  - In this paper, the results on horseradish peroxidase (HRP)-catalyzed oxidative
      polymerization of amine-functionalized fluorene monomer, 2-amino fluorene (AF),
      are reported. The resulting polymer exhibits an exciting molecular structure and
      spectral properties. FT-IR and NMR studies show that the two fluorene units come
      together by forming an intermediate six-membered pyrazine ring and these formed
      dimeric units are linked to the each other through C-C couplings to produce fully
      conjugated polymer structure (AFP). Further characterizations were performed by
      means of GPC, TGA, DSC, SEM, CV (cyclic voltammetry), fluorescence analyses, and
      solubility tests. Optical band gaps of this electroactive polymer was found to be
      2.60 eV. AFP emits red light and its emission maxima is drastically affected by
      the kind of the solvents used. In addition, obtained polymer is soluble in common
      polar and apolar organic solvents.

PMID- 20815397
TI  - Amphoteric agmatine containing polyamidoamines as carriers for plasmid DNA in
      vitro and in vivo delivery.
AB  - In this paper we report on the investigation, as DNA nonviral carriers, of three
      samples of an amphoteric polyamidoamine bearing 4-aminobutylguanidine deriving
      units, AGMA5, AGMA10, and AGMA20, characterized by different molecular weights
      (M(w) 5100, 10100, and 20500, respectively). All samples condensed DNA in
      spherical, positively charged nanoparticles and protected it against enzymatic
      degradation. AGMA10 and AGMA20 polyplexes had average diameters lower than 100
      nm. AGMA5 polyplexes were larger. All polyplexes showed negligible cytotoxicity
      and were internalized in cells. AGMA10 and AGMA20 performed differently from
      AGMA5 as nucleic acid carriers in vitro. AGMA10 and AGMA20 effectively promoted
      transfection, whereas AGMA5 was ineffective. FITC-labeled AGMA10 was prepared and
      the intracellular trafficking of its DNA polyplex was studied. DNA/AGMA10
      polyplex was largely localized inside the nucleus, while AGMA10 concentrated in
      the perinuclear region. DNA/AGMA10 polyplex intravenously administered to mice
      promoted gene expression in liver but not in other organs without detectable
      toxic side effects.

PMID- 20815398
TI  - Genetics of flavonoid, carotenoid, and chlorophyll pigments in melon fruit rinds.
AB  - External color has profound effects on acceptability of agricultural products by
      consumers. Carotenoids and chlorophylls are known to be the major pigments of
      melon (Cucumis melo L.) rinds. Flavonoids (especially chalcones and anthocyanins)
      are also prominent in other fruits but have not been reported to occur in melons
      fruit. We analyzed the pigments accumulating in rinds of different melon
      genotypes during fruit development. We found that melon rind color is based on
      different combinations of chlorophyll, carotenoids, and flavonoids according to
      the cultivar tested and their ratios changed during fruit maturation. Moreover,
      in "canary yellow" type melons, naringenin chalcone, a yellow flavonoid pigment
      previously unknown to occur in melons, has been identified as the major fruit
      colorant in mature rinds. Naringenin chalcone is also prominent in other melon
      types, occurring together with carotenoids (mainly beta-carotene) and
      chlorophyll. Both chlorophyll and carotenoid pigments segregate jointly in an
      F(2) population originating from a cross between a yellow canary line and a line
      with green rind. In contrast, the content of naringenin chalcone segregates as a
      monogenic trait independently to carotenoids and chlorophyll. Transcription
      patterns of key structural phenylpropanoid and flavonoid biosynthetic pathway
      genes were monitored in attempts to explain naringenin chalcone accumulation in
      melon rinds. The transcript levels of CHI were low in both parental lines, but
      C4H, C4L, and CHS transcripts were upregulated in "Noy Amid", the parental line
      that accumulates naringenin chalcone. Our results indicate that naringenin
      chalcone accumulates independently from carotenoids and chlorophyll pigments in
      melon rinds and gives an insight into the molecular mechanism for the
      accumulation of naringenin chalcone in melon rinds.

PMID- 20815399
TI  - Biocompatible, detachable, and free-standing polyelectrolyte multilayer films.
AB  - Self-assembled polyelectrolyte multilayers have gained tremendous popularity over
      the past decade and have been incorporated in diverse applications. However, the
      fabrication of detachable and free-standing polyelectrolyte multilayers (PEMs)
      has proven to be difficult. We report the design of detachable, free-standing,
      and biocompatible PEMs comprised of hyaluronic acid (anionic PE) and chitosan
      (cationic PE). These PEMs can be detached from an underlying inert substrate
      without any postprocessing steps. Our approach enables the fabrication of
      detachable PEMs from a wide range of polyelectrolytes. Cross-linked PEMs
      exhibited greater than 95% weight retention when maintained in phosphate buffered
      saline at 37  degrees C over a seven day period. The PEM thickness was
      approximately 3 MUm for dried films and increased 2-fold under hydration. A
      unique feature of the detachable, free-standing PEMs is their optical
      transparency in the 400-900 nm range under hydrated conditions. The Young's
      modulus of the cross-linked films ranged from 300-400 MPa, rendering these
      detachable free-standing multilayers ideal for biomaterial applications. BALB/c
      3T3 fibroblasts adhered on the PEMs and colonized the entire surface over a six
      day period. The cellular responses, as well as the physical properties,
      demonstrate that the detachable PEM films exhibit tremendous potential for
      applications in biomaterials and tissue engineering.

PMID- 20815400
TI  - Thiourea as a template for photodimerization of azastilbenes.
AB  - In this study we have explored the potential of thiourea (TU) as a template to
      preorient stilbazoles and bispyridylethylenes (azastilbenes) in the crystalline
      state. TU is able to preorient eleven azastilbenes toward dimerization in the
      crystalline state. While cocrystals of these eleven olefins photodimerized to a
      single dimer expected based on crystal packing, pure crystals of these olefins
      either were nonreactive or gave a mixture of dimers. The differential
      photobehavior of the pure crystals and cocrystals highlights the importance of TU
      in templating the olefins in a photoreactive orientation in the crystalline
      state. X-ray crystallographic and photochemical studies have identified a few
      azastilbenes that photodimerize in spite of not being arranged in an ideal
      orientation in the crystalline state. These as well as a few examples already
      reported in the literature suggest that it is important to recognize that
      molecules could experience large amplitude motions in the crystalline state,
      especially when energized by light. Short-term lattice instability caused by
      photoexcitation can be effective in driving a photochemical reaction. Thus one
      should view the crystalline arrangement of molecules upon light exposure as
      "dynamic" rather than "static" as determined from X-ray structure analysis.

PMID- 20815401
TI  - Property-structure relationship of nanoscale ionic materials based on multiwalled
      carbon nanotubes.
AB  - Two categories of nanoscale ionic materials (NIMs) based on multiwalled carbon
      nanotubes (MWCNTs) were obtained. According to the nature of organic modifier and
      the type of interaction, these NIMs can be divided into two categories referred
      to as A-MWCNTs-Fs and I-MWCNTs-Fs, respectively. These MWCNT derivatives were
      virtually solvent-free and showed good flowability even at room temperature. The
      liquidlike manner of these MWCNT derivatives was from their relatively high
      organic content and continual departing-recombining motion of the large organic
      ions as suggested by the comparison of rheological response of the two categories
      of MWCNT-based NIMs. Thermal property and temperature-dependent and strain
      dependent viscoelasticity of MWCNT derivatives were related to the microscopic
      structure of their coating layer and subsequently related to the configuration,
      chemistry, and molecular dimension of modifying molecules to establish the
      property-structure relationship of MWCNT-based NIMs, which could guide our future
      work on NIMs to appropriate and promising applications based on their tunable and
      controllable physical properties.

PMID- 20815402
TI  - Core/shell structured hollow mesoporous nanocapsules: a potential platform for
      simultaneous cell imaging and anticancer drug delivery.
AB  - A potential platform for simultaneous anticancer drug delivery and MRI cell
      imaging has been demonstrated by uniform hollow inorganic core/shell structured
      multifunctional mesoporous nanocapsules, which are composed of functional
      inorganic (Fe(3)O(4), Au, etc.) nanocrystals as cores, a thin mesoporous silica
      shell, and a huge cavity in between. The synthetic strategy for the creation of
      huge cavities between functional core and mesoporous silica shell is based on a
      structural difference based selective etching method, by which solid silica
      middle layer of Fe(2)O(3)@SiO(2)@mSiO(2) (or Au@SiO(2)@mSiO(2)) composite
      nanostructures was selectively etched away while the mesoporous silica shell
      could be kept relatively intact. The excellent biocompatibility of obtained
      multifunctional nanocapsules (Fe(3)O(4)@mSiO(2)) was demonstrated by very low
      cytotoxicity against various cell lines, low hemolyticity against human blood red
      cells and no significant coagulation effect against blood plasma. The cancer cell
      uptake and intracellular location of the nanocapsules were observed by confocal
      laser scanning microscopy and bio-TEM. Importantly, the prepared multifunctional
      inorganic mesoporous nanocapsules show both high loading capacity (20%) and
      efficiency (up to 100%) for doxorubicin simultaneously because of the formation
      of the cavity, enhanced surface area/pore volume and the electrostatic
      interaction between DOX molecules and mesoporous silica surface. Besides, the
      capability of Fe(3)O(4)@mSiO(2) nanocapsules as contrast agents of MRI was
      demonstrated both in vitro and in vivo, indicating the simultaneous imaging and
      therapeutic multifunctionalities of the composite nanocapsules. Moreover, the
      concept of multifunctional inorganic nanocapsules was extended to design and
      prepare Gd-Si-DTPA grafted Au@mSiO(2) nanocapsules for nanomedical applications,
      further demonstrating the generality of this strategy for the preparation of
      various multifunctional mesoporous nanocapsules.

PMID- 20815403
TI  - Synthesis, X-ray structure, magnetic resonance, and DFT analysis of a soluble
      copper(II) phthalocyanine lacking C-H bonds.
AB  - The synthesis, crystal structure, and electronic properties of perfluoro
      isopropyl-substituted perfluorophthalocyanine bearing a copper atom in the
      central cavity (F(64)PcCu) are reported. While most halogenated phthalocyanines
      do not exhibit long-term order sufficient to form large single crystals, this is
      not the case for F(64)PcCu. Its crystal structure was determined by X-ray
      analysis and linked to the electronic properties determined by electron
      paramagnetic resonance (EPR). The findings are corroborated by density functional
      theory (DFT) computations, which agree well with the experiment. X-band
      continuous-wave EPR spectra of undiluted F(64)PcCu powder, indicate the existence
      of isolated metal centers. The electron-withdrawing effect of the perfluoroalkyl
      (R(f)) groups significantly enhances the complexes solubility in organic solvents
      like alcohols, including via their axial coordination. This coordination is
      confirmed by X-band (1)H HYSCORE experiments and is also seen in the solid state
      via the X-ray structure. Detailed X-band CW-EPR, X-band Davies and Mims ENDOR,
      and W-band electron spin-echo-detected EPR studies of F(64)PcCu in ethanol allow
      the determination of the principal g values and the hyperfine couplings of the
      metal, nitrogen, and fluorine nuclei. Comparison of the g and metal hyperfine
      values of F(64)PcCu and other PcCu complexes in different matrices reveals a
      dominant effect of the matrix on these EPR parameters, while variations in the
      ring substituents have only a secondary effect. The relatively strong axial
      coordination occurs despite the diminished covalency of the C-N bonds and
      potentially weakening Jahn-Teller effects. Surprisingly, natural abundance (13)C
      HYSCORE signals could be observed for a frozen ethanol solution of F(64)PcCu. The
      (13)C nuclei contributing to the HYSCORE spectra could be identified as the
      pyrrole carbons by means of DFT. Finally, (19)F ENDOR and easily observable
      paramagnetic NMR were found to relate well to the DFT computations, revealing
      negligible isotropic hyperfine (Fermi contact) contributions. The single-site
      isolation in solution and solid state and the relatively strong coordination of
      axial ligands, both attributed to the introduction of R(f) groups, are features
      important for materials and catalyst design.

PMID- 20815404
TI  - Noninvasive neuron pinning with nanopillar arrays.
AB  - Cell migration in a cultured neuronal network presents an obstacle to selectively
      measuring the activity of the same neuron over a long period of time. Here we
      report the use of nanopillar arrays to pin the position of neurons in a
      noninvasive manner. Vertical nanopillars protruding from the surface serve as
      geometrically better focal adhesion points for cell attachment than a flat
      surface. The cell body mobility is significantly reduced from 57.8 MUm on a flat
      surface to 3.9 MUm on nanopillars over a 5 day period. Yet, neurons growing on
      nanopillar arrays show a growth pattern that does not differ in any significant
      way from that seen on a flat substrate. Notably, while the cell bodies of neurons
      are efficiently anchored by the nanopillars, the axons and dendrites are free to
      grow and elongate into the surrounding area to develop a neuronal network, which
      opens up opportunities for long-term study of the same neurons in connected
      networks.

PMID- 20815405
TI  - Bipolar electrodes: a useful tool for concentration, separation, and detection of
      analytes in microelectrochemical systems.
AB  - Over the past decade, bipolar electrochemistry has emerged from relative
      obscurity to provide a promising new means for integrating electrochemistry into
      lab-on-a-chip systems. This article describes the fundamental operating
      principles of bipolar electrodes, as well as several interesting applications. 

PMID- 20815406
TI  - Optical properties of crystalline-amorphous core-shell silicon nanowires.
AB  - The optical absorption in a nanowire heterostructure consisting of a crystalline
      silicon core surrounded by a conformal shell of amorphous silicon is studied. We
      show that they exhibit extremely high absorption of 95% at short wavelengths
      (lambda < 550 nm) and a concomitant very low absorption of down to less than 2%
      at long wavelengths (lambda > 780 nm). These results indicate that our nanowires
      do not have optically active energy levels in the band gap. The absorption edge
      of silicon nanowires arrays is observed to shift to longer wavelengths as a
      function of the overall nanowire diameter. The near-infrared absorption of the
      nanowire array is significantly better than that of thin film amorphous silicon.
      These properties indicate potential use in large area optoelectronic and
      photovoltaic applications.

PMID- 20815407
TI  - Entropy-driven formation of binary semiconductor-nanocrystal superlattices.
AB  - One of the main reasons for the current interest in colloidal nanocrystals is
      their propensity to form superlattices, systems in which (different) nanocrystals
      are in close contact in a well-ordered three-dimensional (3D) geometry resulting
      in novel material properties. However, the principles underlying the formation of
      binary nanocrystal superlattices are not well understood. Here, we present a
      study of the driving forces for the formation of binary nanocrystal superlattices
      by comparing the formed structures with full free energy calculations. The nature
      (metallic or semiconducting) and the size-ratio of the two nanocrystals are
      varied systematically. With semiconductor nanocrystals, self-organization at high
      temperature leads to superlattices (AlB(2), NaZn(13), MgZn(2)) in accordance with
      the phase diagrams for binary hard-sphere mixtures; hence entropy increase is the
      dominant driving force. A slight change of the conditions results in structures
      that are energetically stabilized. This study provides rules for the rational
      design of 3D nanostructured binary semiconductors, materials with promises in
      thermoelectrics and photovoltaics and which cannot be reached by any other
      technology.

PMID- 20815408
TI  - Patterning of polymer brushes. A direct approach to complex, sub-surface
      structures.
AB  - We report a unique method to directly fabricate complex polymer brush structures
      with nanometer scale features by means of electron beam lithography. Polymer
      brushes for direct patterning were grown from surface-anchored initiator sites
      using atom transfer radical polymerization. Selected monomers (poly(2
      hydroxyethyl methacrylate) and poly(methyl methacrylate)) were used based on
      their ability to readily scission when exposed to radiation. Single step direct
      patterning of polymer brushes is attractive as this eliminates many process
      steps, reducing the possibility of contamination and possibly improving
      resolution. In addition, we report a method to form subsurface polymer brush
      channels with nanometer-scale features. With the chains tethered to a surface, a
      diblock copolymer brush with a negative tone upper layer (polystyrene) and a
      positive tone under layer (poly(methyl methacrylate)) or (poly(2-hydroxyethyl
      methacrylate) were patterned to create channels. In the work presented, the
      direct electron beam patterning behavior of the brushes was studied and
      fabrication of nanochannels was demonstrated. Imaging of the nanopatterned
      surfaces was carried out using atomic force microscopy and fluorescence
      microscopy.

PMID- 20815409
TI  - Time-dependent proteomic iTRAQ analysis of nasal lavage of hairdressers
      challenged by persulfate.
AB  - Hairdressers are frequently exposed to bleaching powder containing persulfates, a
      group of compounds that may induce hypersensitivity in the airways. The mechanism
      causing this reaction is not clear. The aim of this study was to identify changes
      in the nasal lavage fluid proteome after challenge with potassium persulfate in
      hairdressers with bleaching powder-associated rhinitis. Furthermore, we aimed to
      compare their response to that of hairdressers without nasal symptoms, and atopic
      subjects with pollen-associated nasal symptoms. To study the pathogenesis of
      persulfate-associated rhinitis, the response in protein expression from the upper
      airway was assessed by time-dependent proteomic expression analysis of nasal
      lavage fluids. Samples were prepared by pooling nasal lavage fluids from the
      groups at different time points after challenge. Samples were depleted of high
      abundant proteins, labeled with iTRAQ and analyzed by online 2D-nanoLC-MS/MS.
      Differences in the protein pattern between the three groups were observed. Most
      proteins with differentially expressed levels were involved in pathways of lipid
      transportation and antimicrobial activities. The major finding was increased
      abundance of apolipoprotein A-1, 20 min postchallenge, detected solely in the
      group of symptomatic hairdressers. Our results suggest there may be differences
      between the mechanisms responsible for the rhinitis in the symptomatic and atopic
      group.

PMID- 20815410
TI  - An informatics-assisted label-free quantitation strategy that depicts
      phosphoproteomic profiles in lung cancer cell invasion.
AB  - Aberrant protein phosphorylation plays important roles in cancer-related cell
      signaling. With the goal of achieving multiplexed, comprehensive, and fully
      automated relative quantitation of site-specific phosphorylation, we present a
      simple label-free strategy combining an automated pH/acid-controlled IMAC
      procedure and informatics-assisted SEMI (sequence, elution time, mass-to-charge,
      and internal standard) algorithm. The SEMI strategy effectively increased the
      number of quantifiable peptides more than 4-fold in replicate experiments (from
      262 to 1171, p < 0.05, false discovery rate = 0.46%) by using a fragmental
      regression algorithm for elution time alignment followed by peptide cross
      assignment in all LC-MS/MS runs. In addition, the strategy demonstrated good
      quantitation accuracy (10-12%) for standard phosphoprotein and variation less
      than 1.9 fold (within 99% confidence range) in proteome scale and reliable linear
      quantitation correlation (R(2) = 0.99) with 4000-fold dynamic concentrations,
      which was attributed to our reproducible experimental procedure and informatics
      assisted peptide alignment tool to minimize system variations. In an attempt to
      explore metastasis-associated phosphoproteomic alterations in lung cancer, this
      approach was used to delineate differential phosphoproteomic profiles of a lung
      cancer metastasis model. Without sample fractionation, the SEMI algorithm enabled
      quantification of 1796 unique phosphopeptides (false discovery rate = 0.56%)
      corresponding to 854 phosphoproteins from a series of non-small cell lung cancer
      lines with varying degrees of in vivo invasiveness. Nearly 40% of the
      phosphopeptides showed >2-fold change in highly invasive cells; validation of
      phosphoprotein subsets by Western blotting not only demonstrated the consistency
      of data obtained by our SEMI strategy but also revealed that such dramatic
      changes in the phosphoproteome result mostly from translational or post
      translational regulation. Mapping of these differentially expressed
      phosphoproteins in multiple cellular pathways related to cancer invasion and
      metastasis suggests that the site and degree of phosphorylation might have
      distinct patterns or functions in the complex process of cancer progression.

PMID- 20815411
TI  - The oxygen-tolerant hydrogenase I from Aquifex aeolicus weakly interacts with
      carbon monoxide: an electrochemical and time-resolved FTIR study.
AB  - The [NiFe] hydrogenase (Hase I) involved in the aerobic respiration of the
      hyperthermophilic bacterium Aquifex aeolicus shows increased oxygen tolerance and
      thermostability and can form very stable films on pyrolytic graphite electrodes.
      Oxygen-tolerant enzymes, like the ones from A. aeolicus and Ralstonia eutropha,
      are reported to be insensitive to CO inhibition. This is in contrast to known and
      well-characterized (oxygen-sensitive) hydrogenases, for which carbon monoxide is
      a competitive inhibitor. In this study, the interaction of Hase I from A.
      aeolicus with CO is examined using in situ infrared electrochemistry and time
      resolved FTIR spectroscopy. We could observe the formation of a CO adduct state,
      a finding that set the grounds to investigate the affinity of an O(2)-tolerant
      enzyme for binding CO as well as the reversibility of this process. In the case
      of A. aeolicus, this extrinsic CO is shown to be weakly attached and the adduct
      state is light-sensitive at low temperatures. The energetic parameters for the
      rebinding of CO at the active site were estimated from the rate constants of this
      process after photolysis and the results compared to those obtained for standard
      hydrogenases. Formation of a weak Ni-CO bond in the active site of Hase I most
      likely results from the different interaction of this enzyme with inhibitors
      and/or different active site electronic properties to which non standard amino
      acid residues in the vicinity of the active site might contribute.

PMID- 20815412
TI  - Proteomic analysis of the plant-virus interaction in cucumber mosaic virus (CMV)
      resistant transgenic tomato.
AB  - Cucumber mosaic virus (CMV), a member of the Cucumovirus genus, is the causal
      agent of several plant diseases in a wide range of host species, causing
      important economic losses in agriculture. Because of the lack of natural
      resistance genes in most crops, different genetic engineering strategies have
      been adopted to obtain virus-resistant plants. In a previous study, we described
      the engineering of transgenic tomato plants expressing a single-chain variable
      fragment antibody (scFv G4) that are specifically protected from CMV infection.
      In this work, we characterized the leaf proteome expressed during compatible
      plant-virus interaction in wild type and transgenic tomato. Protein changes in
      both inoculated and apical leaves were revealed using two-dimensional gel
      electrophoresis (2-DE) coupled to differential in gel electrophoresis (DIGE)
      technology. A total of 2084 spots were detected, and 50 differentially expressed
      proteins were identified by nanoscale liquid chromatographic-electrospray
      ionization-ion trap-tandem mass spectrometry (nLC-ESI-IT-MS/MS). The majority of
      these proteins were related to photosynthesis (38%), primary metabolism (18%),
      and defense activity (14%) and demonstrated to be actively down regulated by CMV
      in infected leaves. Moreover, our analysis revealed that asymptomatic apical
      leaves of transgenic inoculated plants had no protein profile alteration as
      compared to control wild type uninfected plants demonstrating that virus
      infection is confined to the inoculated leaves and systemic spread is hindered by
      the CMV coat protein (CP)-specific scFv G4 molecules. Our work is the first
      comparative study on compatible plant-virus interactions between engineered
      immunoprotected and susceptible wild type tomato plants, contributing to the
      understanding of antibody-mediated disease resistance mechanisms.

PMID- 20815413
TI  - Nuclear magnetic resonance (NMR) study of the effect of cisplatin on the
      metabolic profile of MG-63 osteosarcoma cells.
AB  - In the present study, (1)H HRMAS NMR spectroscopy was used to assess the changes
      in the intracellular metabolic profile of MG-63 human osteosarcoma (OS) cells
      induced by the chemotherapy agent cisplatin (CDDP) at different times of
      exposure. Multivariate analysis was applied to the cells spectra, enabling
      consistent variation patterns to be detected and drug-specific metabolic effects
      to be identified. Statistical recoupling of variables (SRV) analysis and spectral
      integration enabled the most relevant spectral changes to be evaluated, revealing
      significant time-dependent alterations in lipids, choline-containing compounds,
      some amino acids, polyalcohols, and nitrogenated bases. The metabolic relevance
      of these compounds in the response of MG-63 cells to CDDP treatment is discussed.

PMID- 20815414
TI  - CyberKnife robotic stereotactic radiosurgery.

PMID- 20815415
TI  - The CyberKnife Robotic Radiosurgery System in 2010.
AB  - This review provides a complete technical description of the CyberKnife VSI
      System, the latest addition to the CyberKnife product family, which was released
      in September 2009. This review updates the previous technical reviews of the
      original system version published in the late 1990s. Technical developments over
      the last decade have impacted virtually every aspect of the CyberKnife System.
      These developments have increased the geometric accuracy of the system and have
      enhanced the dosimetric accuracy and quality of treatment, with advanced inverse
      treatment planning algorithms, rapid Monte Carlo dose calculation, and post
      processing tools that allow trade-offs between treatment efficiency and
      dosimetric quality to be explored. This review provides a system overview with
      detailed descriptions of key subsystems. A detailed review of studies of
      geometric accuracy is also included, reporting a wide range of experiments
      involving phantom tests and patient data. Finally, the relationship between
      technical developments and the greatly increased range of clinical applications
      they have allowed is reviewed briefly.

PMID- 20815416
TI  - A pilot study of intensity modulated radiation therapy with hypofractionated
      stereotactic body radiation therapy (SBRT) boost in the treatment of intermediate
      to high-risk prostate cancer.
AB  - Clinical data suggest that large radiation fractions are biologically superior to
      smaller fraction sizes in prostate cancer radiotherapy. The CyberKnife is an
      appealing delivery system for hypofractionated radiosurgery due to its ability to
      deliver highly conformal radiation and to track and adjust for prostate motion in
      real-time. We report our early experience using the CyberKnife to deliver a
      hypofractionated stereotactic body radiation therapy (SBRT) boost to patients
      with intermediate- to high-risk prostate cancer. Twenty-four patients were
      treated with hypofractionated SBRT and supplemental external radiation therapy
      plus or minus androgen deprivation therapy (ADT). Patients were treated with SBRT
      to a dose of 19.5 Gy in 3 fractions followed by intensity modulated radiation
      therapy (IMRT) to a dose of 50.4 Gy in 28 fractions. Quality of life data were
      collected with American Urological Association (AUA) symptom score and Expanded
      Prostate Cancer Index Composite (EPIC) questionnaires before and after treatment.
      PSA responses were monitored; acute urinary and rectal toxicities were assessed
      using Common Toxicity Criteria (CTC) v3. All 24 patients completed the planned
      treatment with an average follow-up of 9.3 months. For patients who did not
      receive ADT, the median pre-treatment PSA was 10.6 ng/ml and decreased in all
      patients to a median of 1.5 ng/ml by 6 months post-treatment. Acute effects
      associated with treatment included Grade 2 urinary and gastrointestinal toxicity
      but no patient experienced acute Grade 3 or greater toxicity. AUA and EPIC scores
      returned to baseline by six months post-treatment. Hypofractionated SBRT combined
      with IMRT offers radiobiological benefits of a large fraction boost for dose
      escalation and is a well tolerated treatment option for men with intermediate- to
      high-risk prostate cancer. Early results are encouraging with biochemical
      response and acceptable toxicity. These data provide a basis for the design of a
      phase II clinical trial.

PMID- 20815417
TI  - CyberKnife radiosurgery for prostate cancer.
AB  - Treatment of prostate cancer with SBRT is an area of significant controversy for
      many in the radiation oncology community despite radiobiologic data that strongly
      suggest the prostate would be an excellent SBRT target. Recently, new data have
      emerged that show promising outcomes with minimal toxicity for CyberKnife SBRT of
      prostate cancer. In the following we present the motivating factors for prostate
      cancer SBRT followed by a critical evaluation of the current literature and
      discussion of the future of prostate cancer treatment with SBRT.

PMID- 20815418
TI  - Image-guided stereotactic body radiation therapy for clinically localized
      prostate cancer: preliminary clinical results.
AB  - Stereotactic body radiotherapy (SBRT) is a new treatment modality for prostate
      cancer. The current study evaluates CyberKnife SBRT and reports toxicity and
      early Prostate-Specific Antigen (PSA) kinetics. From June 2006 to August 2009, 45
      low-and intermediate-risk prostate cancer patients received Cyberknife SBRT of 35
      Gy in five fractions with 95% minimum target coverage. Median follow-up was 20
      months (range 6-42-months). Seventeen patients received androgen-deprivation
      therapy also. Acute complications were mild, short-lived and no greater than
      Grade 2 by RTOG scale. Late toxicities consisted of one patient (2.2%)
      experiencing Grade 2 rectal, one patient (2.2%) Grade 3 and four patients (8.8%)
      with Grade 1 urinary toxicity. PSA in all patients progressively declined from a
      mean 4.7 ng/ml baseline to 1.48 ng/ml at three months, to 0.68 ng/ml at 12 months
      and to 0, 35 ng/ml at 24 months. The 28 hormon-naive patients had the mean PSA
      value of 1.1 ng/ml at one year from a mean 6.65 ng/ml baseline. There was a
      significant PSA value reduction in 11 hormone therapy patients with low baseline
      PSA value (< or = 1 ng/ml) from 0.37 down 0.14 ng/ml (p value 0.0068) at one
      year. Moreover, 14 low risk patients gave better results of mean PSA value than
      17 Intermediate risk patients 0.43 ng/ml vs. 0.93 ng/ml (p value 0.02) at one
      year. No patient had biochemical failure at last follow-up. Hypofractionated SBRT
      appears to have potential against prostate cancer. Low toxicity and encouraging
      biochemical control support its use in early-stage prostate cancer. Results
      encourage further follow-up and larger studies.

PMID- 20815419
TI  - Stereotactic radiotherapy of hepatocellular carcinoma: preliminary results.
AB  - Stereotactic radiotherapy (SRT) offers a treatment option for hepatocellular
      carcinoma (HCC) patients that are not eligible for surgery, embolization,
      chemotherapy, or radiofrequency ablation. We have evaluated the feasibility,
      tolerance and toxicity of SRT for 25 HCC patients who were not eligible for these
      other modalities. The patients (6 women and 19 men) were treated with CyberKnife
      stereotactic radiotherapy using respiratory motion tracking. All patients had
      liver cirrhosis with an Eastern Cooperative Oncology Group (ECOG) performance
      score of less than 2 and pre-treatment Child scores ranging from A5 to B9. A
      total dose of 45 Gy in three fractions of 15 Gy each was prescribed to the 80%
      isodose line (95% of the PTV received 45 Gy) and delivered to the target volume
      over 10 to 12 days. Overall the treatment was well tolerated with two Grade 3
      acute toxicities and no acute Grade 4 toxicities. Late toxicity was minimal with
      all observed late toxicities occurring within the first six months of follow-up.
      Three hepatic recurrences at a distance from the target and one metastasis were
      observed. The actuarial 1- and 2-year local control rate was 95% (95% CI: 69
      95%). At a median overall follow-up of 12,7 months (range, 1-24 months), six of
      the twenty-five (24%) patients have died. Overall actuarial survival at 1- and 2
      years was 79% (95% CI: 52-92%) and 52% (95% CI: 19-78%), respectively. Our
      results suggest promising therapeutic efficacy and good clinical tolerance to
      CyberKnife SRT treatment for HCC patients not eligible for other treatment
      modalities.

PMID- 20815420
TI  - Combined endoscopic endonasal surgery and fractionated stereotactic radiosurgery
      (fSRS) for complex cranial base tumors-early clinical outcomes.
AB  - Endoscopic endonasal surgery (EES) has been shown to be a feasible approach to
      cranial base tumors while reducing post-operative morbidity. Using the endoscopic
      endonasal approach alone or in combination with open approaches may provide
      advantages over conventional approaches. However, the balance between maximal
      resection and minimal injury to neurovascular structures frequently precludes
      gross total resection (GTR). Consequently, adjuvant radiation therapy may be an
      important option to improve local control (LC) of residual disease. In this
      retrospective series, we report clinical outcomes, morbidity, and LC of 40
      patients with cranial base tumors treated with EES +/- combined open approach
      followed by fSRS (CyberKnife, Accuray Inc.). 26 patients had benign disease, 7
      had newly diagnosed malignant disease, and 7 had previously resected malignant
      disease. Surgical outcomes were evaluable in all patients. LC after fSRS was
      evaluable in 39 patients and defined as no evidence of regrowth by MRI, CT, &
      physical examination. GTR was achieved in 12/40. Median post-operative length of
      stay (LOS) was 3 days. In multivariable analysis controlling for anatomic
      location and malignant histology, post-operative complications (n = 10) were
      significantly associated with patients having combined open and EES (p < 0.01, OR
      = 16.9). SRS was delivered in 1-5 sessions to a median marginal dose of 24.9 Gy.
      Median follow-up was 24.7 months (range, 1.5 to 61 months). LC was achieved in
      89.7% (35/39) of evaluable patients. LC was achieved in 11/12 patients who had
      GTR. Median progression-free survival was 19.7 months (21.0 months for benign
      tumors (n = 26), 5.8 months for previously resected malignant disease (n = 7),
      and 21.2 months for newly diagnosed malignant disease (n = 7). Of the 31 patients
      who had symptomatic disease at presentation, 18 (58%) reported complete symptom
      resolution, 9 partial, and 4 no improvement. One patient who received two prior
      courses of radiation therapy developed osteosclerosis (grade III). Other adverse
      events were erythema (grade I, n = 5), nausea (grade II, n = 2), conjunctivitis
      (grade II, n = 1). EES followed by fSRS is a safe and effective management
      strategy for selected cranial base tumors. EES combined with an open surgical
      approach may result in increased complications. However, initial follow-up offers
      encouraging results indicating shorter time to recovery, acceptable LC rates
      compared to conventional approaches, and similar median time to progression for
      benign and newly diagnosed malignant disease.

PMID- 20815421
TI  - Hypofractionated stereotactic radiotherapy for brain metastases: a dosimetric and
      treatment efficiency comparison between volumetric modulated arc therapy and
      intensity modulated radiotherapy.
AB  - A treatment planning comparison study was performed to evaluate the dosimetric
      characteristic and treatment efficiency of volumetric modulated arc therapy with
      step-and-shoot intensity modulated radiotherapy (IMRT) for the hypofractionated
      stereotactic radiotherapy (HFSRT) in patients with multiple brain metastases. CT
      datasets of 10 patients with two to four brain metastases were selected for the
      comparison. Three plans were generated for each case: seven-field step-and-shoot
      IMRT, single (RA1) and double (RA2) arcs with RapidArc technique (RA, Varian
      Medical System). The prescribed dose was 50 Gy in 10 fractions and plans were all
      normalized to the mean dose to the PTV. For PTV, plans aim to achieve at least
      98% of PTV was covered with the 95% of prescription dose, at least 95% of PTV was
      encompassed by the prescription dose, and an over-dosage of 110% of the
      prescription dose was allowed to 5% volume of the PTV. The plans generated using
      three techniques were clinically acceptable. The target conformity and
      homogeneity were improved slightly with RA2 compared to IMRT and RA1. The Paddick
      CI was 0.868 (IMRT), 0.863 (RA1) and 0.895 (RA2), and HI was 7.7 (IMRT), 7.5
      (RA1) and 6.5 (RA2), respectively. Compared with IMRT, the maximum dose in RA2
      plans to the brainstem, left and right optic nerves, left and right lens was
      reduced by 1.6 Gy, 6 Gy, 3 Gy, 1.5 Gy, 1.3 Gy, respectively. The percentage of
      healthy tissue volume receiving 5 Gy was larger with RA1 (56.7%) and RA2 (57.1%)
      than with IMRT (52.9%), while the percentages of volume receiving 15 Gy and 20 Gy
      were smaller with RA1 (27.1%, 18.7%) and RA2 (25%, 16.3%) than with IMRT (28.8%,
      19.1%). No significant difference was observed between RA1 and RA2. The mean
      number of MU per fraction of 5 Gy was 1944 +/- 374 (IMRT), 1199 +/- 173 (RA1) and
      1387 +/- 186 (RA2), respectively. Compared with IMRT, the MUs were reduced by
      36.8% and 27.2% with RA1 and RA2. The pure beam-on time needed per fraction was
      6.5 +/- 1.2 min (IMRT), 1.25 min (RA1) and 2.5 min (RA2), respectively. The beam
      on time for RA1 and RA2 was approximately 80% and 40% less compared to IMRT. In
      conclusion, RA, single arc or double arcs, is a feasible technique with highly
      conformal dose distribution for the HFSRT in patients with oligo brain
      metastases. Compared with IMRT, RA1 provides similar plan quality, while RA2
      achieves slight improvements in PTV coverage and sparing of organs at risk. The
      treatment efficiency, using less monitor units and shorter treatment delivery
      time, is the most obvious advantage.

PMID- 20815422
TI  - Hypofractionated extracranial stereotactic radiotherapy boost for gynecologic
      tumors: a promising alternative to high-dose rate brachytherapy.
AB  - The purpose of this study is to report toxicity and outcome results in patients
      with gynaecological tumours treated with a final boost using extra-cranial
      stereotactic radiotherapy (SRT) with a linac-based micro-multileaf collimator
      technique as an alternative to high-dose rate brachytherapy (HDR-BT). Since
      January 2002, 26 patients with either endometrial (n = 17) or cervical (n = 9)
      cancer were treated according to this protocol: 45-50.4 Gy external radiotherapy
      (RT) to the pelvic +/- para-aortic regions followed by a final SRT boost of 2 x 7
      Gy to the vaginal vault (4-7 day interval between fractions). Median age was 62
      years (37-74 range). Fifteen patients were diagnosed with adenocarcinoma, 7 with
      squamous-cell carcinoma, and 4 with sarcoma. FIGO stage I (n = 17), stage II (n =
      7), and stage III (n = 2). Toxicity was scored according to RTOG/EORTC criteria.
      No severe (> grade-3) acute urinary or low-gastrointestinal (GI) toxicity was
      observed during treatment and up to 3 months after treatment completion. Moderate
      (grade < or = 3) acute urinary or low-GI toxicity was observed in 23% and 35% of
      patients, respectively. After a median follow-up of 47 months (4-77, range), late
      urinary, low-GI, and sexual > or = grade-2 (worst score) has been reported in 4%,
      12% and 29.4% of patients, respectively. The 3-year loco-regional failure-free
      and overall survival rates were 96% and 95%, respectively. Preliminary results on
      feasibility, tolerance, and outcome with SRT are encouraging and may be
      considered a sound alternative to HDR-BT for gynecologic tumors.

PMID- 20815423
TI  - Sensitivity study to evaluate the dosimetric impact of off-axis ratio profiles
      misalignment on TomoTherapy second dose validation.
AB  - Accurate dose planning and delivery are very important in the intensity modulated
      radiation therapy. For helical TomoTherapy dose validation, a TomoTherapy second
      check software, called MU-Tomo, has been developed using archived patient
      documents, initial coordinates and planned dose of the point of calculation, and
      common dosimetric functions. Based on this software, sensitivity studies on 50
      patient cases have been evaluated to show the impact of off-axis ratio profile
      misalignment on point dose calculation. Off-axis ratio is defined as the dose
      profile normalized to its maximum dose value. Sensitivity studies were done for
      three scenarios: oscillating the fluctuation regions of two off-axis profiles,
      shifting the profiles, and rotating the profiles. The result of the oscillation
      trial is linear along the change of longitudinal off-axis ratio (OARy), while
      oscillating the lateral off-axis ratio (OARx) has little influence on the dose
      calculation. For shifting, the variation in the percentage difference from the
      non-shifting value is about 15 times larger in OARy modification than in OARx
      modification. Rotating OARx by +/- 6' gave less than 1.5% +/- 0.20% difference
      compared to the non-rotating value. Rotating OARy by +/- 1' changes the result
      more than 5% +/- 2.69%. Therefore, for helical TomoTherapy dose validation,
      commissioned OARy profiles are more sensitive than OARx to oscillation, shifting
      and rotating. As a result, different tolerances for OARx and OARy may be required
      for annual quality assurance.

PMID- 20815424
TI  - Toolkit for determination of dose-response relations, validation of
      radiobiological parameters and treatment plan optimization based on
      radiobiological measures.
AB  - Accurately determined dose-response relations of the different tumors and normal
      tissues should be estimated and used in the clinic. The aim of this study is to
      demonstrate developed tools that are necessary for determining the dose-response
      parameters of tumors and normal tissues, for clinically verifying already
      published parameter sets using local patient materials and for making use of all
      this information in the optimization and comparison of different treatment plans
      and radiation techniques. One of the software modules (the Parameter
      Determination Module) is designed to determine the dose-response parameters of
      tumors and normal tissues. This is accomplished by performing a maximum
      likelihood fitting to calculate the best estimates and confidence intervals of
      the parameters used by different radiobiological models. Another module of this
      software (the Parameter Validation Module) concerns the validation and
      compatibility of external or reported dose-response parameters describing tumor
      control and normal tissue complications. This is accomplished by associating the
      expected response rates, which are calculated using different models and
      published parameter sets, with the clinical follow-up records of the local
      patient population. Finally, the last module of the software (the Radiobiological
      Plan Evaluation Module) is used for estimating and optimizing the effectiveness a
      treatment plan in terms of complication-free tumor control, P(+). The use of the
      Parameter Determination Module is demonstrated by deriving the dose-response
      relation of proximal esophagus from head and neck cancer radiotherapy. The
      application of the Parameter Validation Module is illustrated by verifying the
      clinical compatibility of those dose-response parameters with the examined
      treatment methodologies. The Radiobiological Plan Evaluation Module is
      demonstrated by evaluating and optimizing the effectiveness of head and neck
      cancer treatment plans. The results of the radiobiological evaluation are
      compared against dosimetric criteria. The presented toolkit appears to be very
      convenient and efficient for clinical implementation of radiobiological modeling.
      It can also be used for the development of a clinical data and health information
      database for assisting the performance of epidemiological studies and the
      collaboration between different institutions within research and clinical
      frameworks.

PMID- 20815425
TI  - Vowel identification by younger and older listeners: relative effectiveness of
      vowel edges and vowel centers.
AB  - Young normal-hearing (YNH) and older normal-hearing (ONH) listeners identified
      vowels in naturally produced /bVb/ syllables and in modified syllables that
      consisted of variable portions of the vowel edges (silent-center [SC] stimuli) or
      vowel center (center-only [CO] stimuli). Listeners achieved high levels of
      performance for all but the shortest stimuli, indicating that they were able to
      access vowel cues throughout the syllable. ONH listeners performed similarly to
      YNH listeners for most stimuli, but performed more poorly for the shortest CO
      stimuli. SC and CO stimuli were equally effective in supporting vowel
      identification except when acoustic information was limited to 20 ms.

PMID- 20815426
TI  - Three-dimensional source tracking in an uncertain environment via Bayesian
      marginalization.
AB  - This paper develops a non-linear Bayesian marginalization approach for three
      dimensional source tracking in shallow water with uncertain environmental
      properties. The algorithm integrates the posterior probability density via a
      combination of Metropolis-Hastings sampling over environmental and bearing model
      parameters and Gibbs sampling over source range/depth, with track constraints on
      source velocity applied. Marginal distributions for source range/depth and source
      bearing are derived, with source position uncertainties estimated from the
      distributions. The Viterbi algorithm is applied to obtain the most probable three
      dimensional track. The approach is applied to experimental narrowband data
      recorded on a bottom-moored horizontal line array in the Barents Sea.

PMID- 20815427
TI  - Perception of longitudinal components in piano string vibrations.
AB  - This paper investigates the audibility of longitudinal components in piano string
      vibrations with listening tests. The recorded fortissimo sounds of two grand and
      one upright pianos have been resynthesized with and without longitudinal
      components and used in ABX type listening tests. Results suggest that the
      longitudinal components are audible up to note C(5). However, a second test
      seeking the importance of the difference shows that the effect of longitudinal
      components for the range A(3)-C(5) is subtle. This means that modeling the
      phenomenon up to around note A(3) only is acceptable for sound synthesis
      applications.

PMID- 20815428
TI  - Flow-induced vibratory response of idealized versus magnetic resonance imaging
      based synthetic vocal fold models.
AB  - Recent vocal fold vibration studies have used models defined using idealized
      geometry. Although these models exhibit important similarities with human vocal
      fold vibration, some aspects of their motion are less than realistic. In this
      report it is demonstrated that more realistic motion may be obtained when using
      geometry derived from magnetic resonance imaging (MRI) data. The dynamic response
      of both idealized and MRI-based synthetic vocal fold models are presented. MRI
      based model improvements include evidence of mucosal wave-like motion and less
      vertical movement. Limitations of the MRI-based model are discussed and
      suggestions for further synthetic model development are offered.

PMID- 20815429
TI  - Modeling deep ocean shipping noise in varying acidity conditions.
AB  - Possible future changes of ambient shipping noise at 0.1-1 kHz in the North
      Pacific caused by changing seawater chemistry conditions are analyzed with a
      simplified propagation model. Probable decreases of pH would cause meaningful
      reduction of the sound absorption coefficient in near-surface ocean water for
      these frequencies. The results show that a few decibels of increase may occur in
      100 years in some very quiet areas very far from noise sources, with small
      effects closer to noise sources. The use of ray physics allows sound energy
      attenuated via volume absorption and by the seafloor to be compared.

PMID- 20815430
TI  - Ocean acidification and its impact on ocean noise: phenomenology and analysis.
AB  - Ocean acidification has been observed since the beginning of the industrial era
      and is expected to further reduce ocean pH in the future. A significant increase
      in ocean noise has been suggested based upon the percentage change in acoustic
      absorption coefficient at low frequencies. Presented here is an analysis using
      transmission loss models of all relevant loss mechanisms for three environments
      experiencing a significant near-surface pH reduction of 8.1-7.4. Results show no
      observable change in the shallow water and surface duct environments, and a
      statistically insignificant change of less than 0.5 dB for all frequencies in the
      deep water environment.

PMID- 20815431
TI  - A computational assessment of the sensitivity of ambient noise level to ocean
      acidification.
AB  - Low-frequency sound propagating through the ocean is partly attenuated by the pH
      dependent boric acid relaxation process. Thus, the uptake of increased levels of
      atmospheric CO(2) by seawater, leading to reduced pH, has potential to change
      ambient noise levels. An important question is: By how much? Here, changes in
      ambient noise level due to hypothetical changes in seawater pH have been
      calculated at three receiver locations for years 1960 and 2250. The calculations
      used a range dependent propagation model that was applied to realistic
      environments based on climatology. Model results indicate changes in noise levels
      less than 0.21 dB are anticipated.

PMID- 20815432
TI  - Automatic identification of individual killer whales.
AB  - Following the successful use of HMM and GMM models for classification of a set of
      75 calls of northern resident killer whales into call types [Brown, J. C., and
      Smaragdis, P., J. Acoust. Soc. Am. 125, 221-224 (2009)], the use of these same
      methods has been explored for the identification of vocalizations from the same
      call type N2 of four individual killer whales. With an average of 20
      vocalizations from each of the individuals the pairwise comparisons have an
      extremely high success rate of 80 to 100% and the identifications within the
      entire group yield around 78%.

PMID- 20815433
TI  - Convolutional modeling of diffraction effects in pulse-echo ultrasound imaging.
AB  - A model is presented for pulse-echo imaging of three-dimensional, linear, weakly
      scattering continuum media by ultrasound array transducers. The model accounts
      for the diffracted fields of focused array subapertures in both transmit and
      receive modes, multiple transmit and receive focal zones, frequency-dependent
      attenuation, and aberration caused by mismatched medium and beamformer sound
      speeds. For a given medium reflectivity function, computation of a B-scan
      requires evaluation of a depth-dependent transmit/receive beam product, followed
      by two one-dimensional convolutions and a one-dimensional summation. Numerical
      results obtained using analytic expressions for transmit and receive beams agree
      favorably with measured B-scan images and speckle statistics.

PMID- 20815434
TI  - Phase-coherent communications without explicit phase tracking.
AB  - Phase-coherent communications typically requires a reliable phase-tracking
      algorithm. An initial phase estimate with training symbols allows a receiver to
      compensate for a motion-induced Doppler shift. Following the training period,
      however, explicit phase tracking can be avoided in time reversal communications
      that has been implemented on a block-by-block basis to accommodate time-varying
      channels. This is accomplished by a smaller block size and adaptive channel
      estimation using previously detected symbols on a symbol-by-symbol basis. The
      proposed time reversal approach without explicit phase tracking is demonstrated
      using experimental data (12-20 kHz) in shallow water.

PMID- 20815435
TI  - Diffraction from the edge of a thin elastic half plane and implications for panel
      measurements.
AB  - Solutions for the diffraction of a plane wave from the edge of a semi-infinite,
      thin elastic plate are presented. A thin plate formulation that takes into
      account the coupling into both symmetric and antisymmetric waves on the plate is
      used. The symmetric contributions are found to be small for steel in water but
      can be significant for plastic plates. Expansions in terms of the fluid loading
      parameter are used in the far field of the edge to explore the effect of the
      diffraction from a single edge on transmission measurements. Examples for steel
      and polymethylmethacrylate in water are presented.

PMID- 20815436
TI  - Experimental demonstration of the utility of pressure sensitivity kernels in time
      reversal.
AB  - Pressure sensitivity kernels were recently applied to time-reversal acoustics in
      an attempt to explain the enhanced stability of the time-reversal focal spot
      [Raghukumar et al., J. Acoust. Soc. Am. 124, 98-112 (2008)]. The theoretical
      framework developed was also used to derive optimized source functions, closely
      related to the inverse filter. The use of these optimized source functions
      results in an inverse filter-like focal spot which is more robust to medium sound
      speed fluctuations than both time-reversal and the inverse filter. In this paper
      the theory is applied to experimental data gathered during the Focused Acoustic
      Fields experiment, conducted in 2005, north of Elba Island in Italy. Sensitivity
      kernels are calculated using a range-independent sound-speed profile, for a
      geometry identical to that used in the experiment, and path sensitivities are
      identified with observed arrivals. The validity of the kernels in tracking time
      evolving Green's functions is studied, along with limitations that result from a
      linearized analysis. An internal wave model is used to generate an ensemble of
      sound speed profiles, which are then used along with the calculated sensitivity
      kernels to derive optimized source functions. Focal spots obtained using the
      observed Green's functions with these optimized source functions are then
      compared to those obtained using time-reversal and the inverse-filter. It is
      shown that these functions are able to provide a focal spot superior to time
      reversal while being more robust to sound speed fluctuations than the inverse
      filter or time-reversal.

PMID- 20815437
TI  - A generalized approach for efficient finite element modeling of elastodynamic
      scattering in two and three dimensions.
AB  - A robust and efficient technique for predicting the far-field scattering behavior
      for an arbitrarily-shaped defect in a generally anisotropic medium is presented
      that can be implemented in a commercial FE package. The spatial size of the
      modeling domain around the defect is as small as possible to minimize
      computational expense and a minimum number of models are executed. The method is
      based on an integral representation of a wave field in a homogeneous anisotropic
      medium. A plane incident mode is excited by applying suitable forces at nodes on
      a surface that encloses the scatterer. The scattered wave field is measured at
      monitoring nodes on a concentric surface and then decomposed into far-field
      scattering amplitudes of different modes in different directions. Example results
      for 2D and 3D bulk wave scattering in isotropic material and guided wave
      scattering are presented. Modeling accuracy is examined in various ways,
      including a comparison with the analytical solutions and calculation of the
      energy balance.

PMID- 20815438
TI  - Low sidelobe limited diffraction beams in the nonlinear regime.
AB  - In linear propagation, sidelobe levels of Bessel limited diffraction beams are
      only about 8 dB down relative to the mainlobe. In the nonlinear regime, these
      beams will have a region near the source where the side-lobe level of the second
      harmonic is 16 dB down, but this region has usually been considered to be so
      small that it is of little practical interest. In this paper it is shown that
      when there are only 1 to 3 sidelobes in a finite aperture Bessel beam, the second
      harmonic field will have low sidelobes for distances up to half of the depth of
      field. This result is backed up by simulations. In a medium with absorption,
      previous theory has shown that the sidelobes of the Bessel beam will also be
      reduced but only for absorption that was too high to be of practical use.
      Simulations presented here show that for breast tissue, which only has about 10%
      of the absorption of previous criteria, one will still get sidelobes which are
      comparable to that of a rectangular aperture even when the sidelobes would be
      high in a non-absorbing medium.

PMID- 20815439
TI  - A micro-machined piezoelectric flexural-mode hydrophone with air backing: a
      hydrostatic pressure-balancing mechanism for integrity preservation.
AB  - Although an air-backed thin plate is an effective sound receiver structure, it is
      easily damaged via pressure unbalance caused by external hydrostatic pressure. To
      overcome this difficulty, a simple pressure-balancing module is proposed. Despite
      its small size and relative simplicity, with proper design and operation, micro
      channel structure provides a solution to the pressure-balancing problem. If the
      channel size is sufficiently small, the gas-liquid interface may move back and
      forth without breach by the hydrostatic pressure since the surface tension can
      retain the interface surface continuously. One input port of the device is opened
      to an intermediate liquid, while the other port is connected to the air-backing
      chamber. As the hydrostatic pressure increases, the liquid in the micro-channel
      compresses the air, and the pressure in the backing chamber is then equalized to
      match the external hydrostatic pressure. To validate the performance of the
      proposed mechanism, a micro-channel prototype is designed and integrated with the
      piezoelectric micro-machined flexural sensor developed in our previous work. The
      working principle of the mechanism is experimentally verified. In addition, the
      effect of hydrostatic pressure on receiving sensitivity is evaluated and compared
      with predicted behavior.

PMID- 20815440
TI  - A micro-machined piezoelectric flexural-mode hydrophone with air backing: benefit
      of air backing for enhancing sensitivity.
AB  - A micro-machined underwater acoustic receiver that utilizes the flexural
      vibration mode of a silicon thin plate and piezoelectric transduction material
      was investigated. In particular, air was used as the backing material for the
      hydrophone in order to improve sensitivity in the audible frequency range. To
      evaluate the effects of air backing on receiving sensitivity, a transduction
      model incorporating mechanical/electrical/acoustical design parameters was used
      in designing a piezoelectric micro-machined hydrophone. The sensitivity and
      displacement responses of the sensor were simulated using the model for air
      backing and water backing cases, and the benefit of using air backing to enhance
      sensitivity was confirmed. The micro-machined piezoelectric transducer was
      fabricated, assembled in the shape of a hydrophone, and tested to ascertain its
      characteristics as an underwater sensor. These characteristics, such as frequency
      response and sensitivity, were measured and compared with the simulated results.

PMID- 20815441
TI  - Objective evaluation of the sweet spot size in spatial sound reproduction using
      elevated loudspeakers.
AB  - In a previous study, three crosstalk cancellation techniques were evaluated and
      compared under different conditions. Least-squares approximations in the
      frequency and time domain were evaluated along with a method based on minimum
      phase decomposition and a frequency independent delay. In general, the least
      squares methods outperformed the method based on the minimum-phase decomposition.
      However, the evaluation was only done for the best-case scenario, where the
      transfer functions used to design the filters correspond to the listener's
      transfer functions and his/her location and orientation relative to the
      loudspeakers. This paper presents a follow-up evaluation of the performance of
      the three inversion techniques when the above mentioned conditions are relaxed. A
      setup to measure the sweet spot of different loudspeaker arrangements is
      described. The sweet spot was measured for 21 different loudspeaker
      configurations, including two- and four-channel setups. Lateral and frontal
      displacement were measured along with head rotations. The setups were evaluated
      at different elevation angles. The results suggest that when the loudspeakers are
      placed at elevated positions, a wider effective area is obtained. Additionally,
      the two-channel configurations showed to be more robust to head misalignments
      than the four-channel configurations.

PMID- 20815442
TI  - Experimental validation of alternate integral-formulation method for predicting
      acoustic radiation based on particle velocity measurements.
AB  - This paper presents experimental validation of an alternate integral-formulation
      method (AIM) for predicting acoustic radiation from an arbitrary structure based
      on the particle velocities specified on a hypothetical surface enclosing the
      target source. Both the normal and tangential components of the particle velocity
      on this hypothetical surface are measured and taken as the input to AIM codes to
      predict the acoustic pressures in both exterior and interior regions. The results
      obtained are compared with the benchmark values measured by microphones at the
      same locations. To gain some insight into practical applications of AIM, laser
      Doppler anemometer (LDA) and double hotwire sensor (DHS) are used as measurement
      devices to collect the particle velocities in the air. Measurement limitations of
      using LDA and DHS are discussed.

PMID- 20815443
TI  - Vibration of elliptic cylindrical shells: higher order shell theory.
AB  - The equations for the free vibration of an elliptic cylindrical shell of constant
      thickness were derived using a Ritz approach. A higher order shell theory is
      employed that includes the effects of shear deformation, rotary inertia, and
      symmetric and antisymmetric thickness stretch deformations. The frequency
      wavenumber spectrum has seven branches: flexural, extensional, torsional, two
      thickness shear, and two thickness stretch. The resulting seven coupled algebraic
      equations are symmetric and positive definite. The shell has a constant
      thickness, h, finite length, L, and is "simply supported" at its ends, (z=0,L),
      where z is the axial coordinate. The elliptic cross-section is defined by the
      shape parameter, a, and the half-length of the major axis, l. The modal solutions
      are expanded in a doubly infinite series of comparison functions in terms of
      circular functions in the angular and axial coordinates. Numerical results for
      the natural frequencies were obtained for two values of h/l and L/l, and various
      shape parameters, including the limiting case of a simply supported cylindrical
      shell (a approximately 100).

PMID- 20815444
TI  - Expansions of reflected-transmitted signals to estimate the slow wave strength in
      fluid-saturated porous layers.
AB  - A method for estimating the strength of the slow wave in the modes propagating in
      porous layers is presented. It is based upon expansions on transition terms which
      are linear combinations of the reflection and transmission coefficients. Suitable
      forms of these coefficients are needed and it is shown how they can be obtained.
      Both open pore and sealed pore boundary conditions are investigated. It is shown
      that the zeroth-order and the first-order terms of the expansions suffice to
      describe accurately the modes and to estimate the strength of the slow wave.
      Approximations of the absorption coefficient by the porous layer can be deduced.
      Angles of incidence above and below the critical angle of the shear wave are
      considered. Comparisons between theory and experiments for the two types of
      boundary conditions are presented at normal incidence for the transition terms.

PMID- 20815445
TI  - Hertzian impact: experimental study of the force pulse and resulting stress
      waves.
AB  - Ball impact has long been used as a repeatable source of stress waves in solids.
      The amplitude and frequency content of the waves are a function of the force-time
      history, or force pulse, that the ball imposes on the massive body. In this
      study, Glaser-type conical piezoelectric sensors are used to measure vibrations
      induced by a ball colliding with a massive plate. These measurements are compared
      with theoretical estimates derived from a marriage of Hertz theory and elastic
      wave propagation. The match between experiment and theory is so close that it not
      only facilitates the absolute calibration the sensors but it also allows the
      limits of Hertz theory to be probed. Glass, ruby and hardened steel balls 0.4 to
      2.5 mm in diameter were dropped onto steel, glass, aluminum, and
      polymethylmethacrylate plates at a wide range of approach velocities, delivering
      frequencies up to 1.5 MHz into these materials. Effects of surface properties and
      yielding of the plate material were analyzed via the resulting stress waves and
      simultaneous measurements of the ball's coefficient of restitution. The sensors
      are sensitive to surface normal displacements down to about +/-1 pm in the
      frequency range of 20 kHz to over 1 MHz.

PMID- 20815446
TI  - Analytical modeling of sound transmission across finite aeroelastic panels in
      convicted fluids.
AB  - An analytical approach is formulated to account for the effects of mean flow on
      sound transmission across a simply supported rectangular aeroelastic panel. The
      application of the convected wave equation and the displacement continuity
      condition at the fluid-panel interfaces ensures the exact handling of the complex
      aeroelastic coupling between panel vibration and fluid disturbances. To explore
      the mean flow effects on sound transmission, three different cases (i.e., mean
      flow on incident side only, on radiating side only, and on both sides) are
      separately considered in terms of refraction angular relations and sound
      transmission loss (STL) plots. Obtained results show that the influence of the
      incident side mean flow upon sound penetration is significantly different from
      that of the transmitted side mean flow. The contour plot of refraction angle
      versus incident angle for the case when the mean flow is on the transmitted side
      is just a reverse of that when the mean flow is on the incident side. The
      aerodynamic damping effects on the transmission of sound are well captured by
      plotting the STL as a function of frequency for varying Mach numbers. However, as
      the Mach number is increased, the coincidence dip frequency increases when the
      flow is on the incident side but remains unchanged when in the flow is on the
      radiating side. In the most general case when the fluids on both sides of the
      panel are convecting, the refraction angular relations are significantly
      different from those when the fluid on one side of the panel is moving and that
      on the other side is at rest.

PMID- 20815447
TI  - Double panel with skyhook active damping control units for control of sound
      radiation.
AB  - This paper presents an experimental study on decentralized velocity feedback
      control on a double panel consisting of an external aluminum panel and a
      honeycomb trim panel. The decentralized feedback loops are formed by a 3x3 array
      of coil-magnet electrodynamic actuators that react off the trim panel and a
      lightweight stiff frame structure located in the air gap between the two panels.
      Microelectromechanical systems (MEMS) accelerometers are located on the opposite
      side of the trim panel in correspondence to the electrodynamic actuators. The
      grid structure is designed to provide an inertial reference to the actuators. In
      this way the velocity feedback control loops produce skyhook active damping on
      the double panel, which minimizes the vibrational response and sound radiation of
      the trim panel at low audio frequencies. Two configurations are considered where
      the grid structure is either weakly coupled or strongly coupled to the external
      panel. Both stability and control performance of the two configurations are
      analyzed experimentally. The study shows that the control configuration with the
      weakly coupled grid structure enables the implementation of larger stable
      feedback control gains, which lead to reductions of the sound radiated by the
      trim panel between 10 and 30 dB for the first seven resonance peaks.

PMID- 20815448
TI  - Noise prediction of a subsonic turbulent round jet using the lattice-Boltzmann
      method.
AB  - The lattice-Boltzmann method (LBM) was used to study the far-field noise
      generated from a Mach, M(j)=0.4, unheated turbulent axisymmetric jet. A
      commercial code based on the LBM kernel was used to simulate the turbulent flow
      exhausting from a pipe which is 10 jet radii in length. Near-field flow results
      such as jet centerline velocity decay rates and turbulence intensities were in
      agreement with experimental results and results from comparable LES studies. The
      predicted far field sound pressure levels were within 2 dB from published
      experimental results. Weak unphysical tones were present at high frequency in the
      computed radiated sound pressure spectra. These tones are believed to be due to
      spurious sound wave reflections at boundaries between regions of varying voxel
      resolution. These "VR tones" did not appear to bias the underlying broadband
      noise spectrum, and they did not affect the overall levels significantly. The LBM
      appears to be a viable approach, comparable in accuracy to large eddy
      simulations, for the problem considered. The main advantages of this approach
      over Navier-Stokes based finite difference schemes may be a reduced computational
      cost, ease of including the nozzle in the computational domain, and ease of
      investigating nozzles with complex shapes.

PMID- 20815449
TI  - Annoyance from industrial noise: indicators for a wide variety of industrial
      sources.
AB  - In the study of noises generated by industrial sources, one issue is the variety
      of industrial noise sources and consequently the complexity of noises generated.
      Therefore, characterizing the environmental impact of an industrial plant
      requires better understanding of the noise annoyance caused by industrial noise
      sources. To deal with the variety of industrial sources, the proposed approach is
      set up by type of spectral features and based on a perceptive typology of steady
      and permanent industrial noises comprising six categories. For each perceptive
      category, listening tests based on acoustical factors are performed on noise
      annoyance. Various indicators are necessary to predict noise annoyance due to
      various industrial noise sources. Depending on the spectral features of the
      industrial noise sources, noise annoyance indicators are thus assessed. In case
      of industrial noise sources without main spectral features such as broadband
      noise, noise annoyance is predicted by the A-weighted sound pressure level L(Aeq)
      or the loudness level L(N). For industrial noises with spectral components such
      as low-frequency noises with a main component at 100 Hz or noises with spectral
      components in middle frequencies, indicators are proposed here that allow good
      prediction of noise annoyance by taking into account spectral features.

PMID- 20815450
TI  - A theoretical framework for quantitatively characterizing sound field diffusion
      based on scattering coefficient and absorption coefficient of walls.
AB  - This paper describes the development of a theoretical framework for
      quantitatively characterizing sound field diffusion based on scattering
      coefficient and absorption coefficient of walls. The concepts of equivalent
      scattering area, equivalent scatter reflection area, average scattering
      coefficient and average scatter reflection coefficient are introduced in order to
      express all walls' capability of scatter in a room. Using these concepts and the
      mean free path, scatter-to-absorption ratio, mean scatter time and diffusion time
      are defined in order to evaluate degree of diffusion of a space. Furthermore the
      effect of spatial scattering objects to sound field diffusion is formulated. In
      addition the time variation of specular and scattered components in a room
      impulse response is formulated. The verification of these characterization
      methods was performed with computer simulations based on the sound ray tracing
      method. The results supported that the ideas presented are basically valid.

PMID- 20815451
TI  - Diffusive benefits of cylinders in front of a Schroeder diffuser.
AB  - A numerical investigation is performed into the diffusive effects of cylinders
      positioned in front of a Schroeder diffuser. A regular line of cylinders is shown
      to offer notable improvements to diffusion from a periodic Schroeder device,
      provided lateral cylinder spacing is incommensurable with the Schroeder period
      width. Further investigation considers angular dependence and low frequency
      results in greater detail, as well as the effects on narrowband and modulated
      Schroeder devices. An optimization procedure is subsequently performed to
      investigate the effects of an irregular cylinder arrangement, which provides
      further diffusive benefits.

PMID- 20815452
TI  - Room volume classification from room impulse response using statistical pattern
      recognition and feature selection.
AB  - Classification of the room volume from the room impulse response (RIR) can be
      useful in acoustic scene analysis applications, using RIR that is provided
      directly, or estimated from audio recordings. Current methods for estimating the
      room volume from the RIR require the source-to-receiver distance, and may be
      sensitive to differences in absorption. A room volume classification method is
      presented that does not require the source-to-receiver distance, and which is
      potentially robust to differences in absorption. Room volume features are defined
      that are related to the room volume and may be extracted from the RIR. Gaussian
      mixture models are trained to model room volume classes. Room volume is
      classified according to a maximum likelihood criterion that is normalized with a
      background model. Feature selection is performed with different classification
      error criteria. Both simulated and measured RIRs were examined, achieving an
      equal error rate of 0.1% and 19.1%, respectively.

PMID- 20815453
TI  - Ototoxicity risk assessment combining distortion product otoacoustic emissions
      with a cisplatin dose model.
AB  - An objective method for identifying ototoxic hearing loss among patients
      receiving cisplatin is necessary since the ability of patients to take a
      behavioral test may change over the course of treatment. Data from 56 monitoring
      visits by 19 Veterans taking cisplatin were used to identify combinations of
      distortion-product otoacoustic emission (DPOAE) metrics and ototoxicity risk
      factors that best identified ototoxic hearing loss. Models were tested that
      incorporated DPOAE metrics generated statistically using partial least-squares
      analysis. Models were also tested that incorporated a priori DPOAE change
      criteria, such as a minimum DPOAE level shift of 6 dB. Receiver Operating
      Characteristic analysis was used to compare the accuracy of these models. The
      best performing model incorporated weighted combinations of pre-treatment
      hearing, cumulative cisplatin dose and DPOAE metrics that were determined using
      partial least-squares and evaluated over a quarter octave range near each
      subjects' high frequency DPOAE limit. Using this model and the DPOAE recording
      methods described herein, the chance of ototoxic hearing change can be determined
      at any given observed change in DPOAE level. This approach appears to provide an
      accurate and rapid ototoxicity risk assessment (ORA) that once validated can be
      used clinically.

PMID- 20815454
TI  - The interplay between active hair bundle motility and electromotility in the
      cochlea.
AB  - The cochlear amplifier is a nonlinear active process providing the mammalian ear
      with its extraordinary sensitivity, large dynamic range and sharp frequency
      tuning. While there is much evidence that amplification results from active force
      generation by mechanosensory hair cells, there is debate about the cellular
      processes behind nonlinear amplification. Outer hair cell electromotility has
      been suggested to underlie the cochlear amplifier. However, it has been shown in
      frog and turtle that spontaneous movements of hair bundles endow them with a
      nonlinear response with increased sensitivity that could be the basis of
      amplification. The present work shows that the properties of the cochlear
      amplifier could be understood as resulting from the combination of both hair
      bundle motility and electromotility in an integrated system that couples these
      processes through the geometric arrangement of hair cells embedded in the
      cochlear partition. In this scenario, the cochlear partition can become a dynamic
      oscillator which in the vicinity of a Hopf bifurcation exhibits all the key
      properties of the cochlear amplifier. The oscillatory behavior and the
      nonlinearity are provided by active hair bundles. Electromotility is largely
      linear but produces an additional feedback that allows hair bundle movements to
      couple to basilar membrane vibrations.

PMID- 20815455
TI  - Different models of the active cochlea, and how to implement them in the state
      space formalism.
AB  - The state-space formalism [Elliott S. J., et al. (2007). J. Acoust. Soc. Am. 122,
      2759-2771] allows one to discretize cochlear models in a straightforward matrix
      form and to modify the main physical properties of the cochlear model by changing
      the position and functional form of a few matrix elements. Feed-forward and feed
      backward properties can be obtained by simply introducing off-diagonal terms in
      the matrixes expressing the coupling between the dynamical variables and the
      additional active pressure on the basilar membrane. Some theoretical issues
      related to different cochlear modeling choices, their implementation in a state
      space scheme, and their physical consequences on the cochlear phenomenology, as
      predicted by numerical simulations, are discussed. Different schematizations of
      the active term describing the behavior of the outer hair cell's feedback
      mechanism, including nonlinear and nonlocal dependences on either pressure or
      basilar membrane displacement, are also discussed, showing their effect on some
      measurable cochlear properties.

PMID- 20815456
TI  - The time course of cochlear gain reduction measured using a more efficient
      psychophysical technique.
AB  - In a previous study it was shown that an on-frequency precursor intended to
      activate the medial olivocochlear reflex (MOCR) at the signal frequency reduces
      the gain estimated from growth-of-masking (GOM) functions. This is called the
      temporal effect (TE). In Expt. 1 a shorter method of measuring this change in
      gain is established. GOM functions were measured with an on- and off-frequency
      precursor presented before the masker and signal, and used to estimate
      Input/Output functions. The change in gain estimated in this way was very similar
      to that estimated from comparing two points measured with a single fixed masker
      level on the lower legs of the GOM functions. In Expt. 2, the TE was measured as
      a function of precursor duration and signal delay. For short precursor durations
      and short delays the TE increased (buildup) or remained constant as delay
      increased, then decreased. The TE also increased with precursor duration for the
      shortest delay. The results were fitted with a model based on the time course of
      the MOCR. The model fitted the data well, and predicted the buildup. This buildup
      is not consistent with exponential decay predicted by neural adaptation or
      persistence of excitation.

PMID- 20815457
TI  - Encoding pitch contours using current steering.
AB  - This study investigated cochlear implant (CI) users' ability to perceive pitch
      cues from time-varying virtual channels (VCs) to identify pitch contours. Seven
      CI users were tested on apical, medial, and basal electrode pairs with stimulus
      durations from 100 to 1000 ms. In one stimulus set, 9 pitch contours were created
      by steering current between the component electrodes and the VC halfway between
      the electrodes. Another stimulus set only contained 3 pitch contours (flat,
      falling, and rising). VC discrimination was also tested on the same electrodes.
      The total current level of dual-electrode stimuli was linearly interpolated
      between those of single-electrode stimuli to minimize loudness changes. The
      results showed that pitch contour identification (PCI) scores were similar across
      electrode locations, and significantly improved at longer durations. For
      durations longer than 300 ms, 2 subjects had nearly perfect 9-contour
      identification, and 5 subjects perfectly identified the 3 basic contours. Both
      PCI and VC discrimination varied greatly across subjects. Cumulative d(') values
      for VC discrimination were significantly correlated with 100-, 200-, and 500-ms
      PCI scores. These results verify the feasibility of encoding pitch contours using
      current steering, and suggest that identification of such pitch contours strongly
      relies on CI users' sensitivity to VCs.

PMID- 20815458
TI  - Accounting quantitatively for sensitivity to envelope-based interaural temporal
      disparities at high frequencies.
AB  - Bernstein and Trahiotis [(2009). J. Acoust. Soc. Am. 125, 3234-3242] reported
      threshold interaural temporal disparities (ITDs) conveyed by the envelopes of 4
      kHz-centered "raised-sine" stimuli. A raised-sine stimulus consists of a carrier
      modulated by a sinusoid raised to an exponent. Such stimuli permitted Bernstein
      and Trahiotis to vary, independently, stimulus modulation frequency, modulation
      depth, and "relative peakedness/deadtime." An interaural correlation-based model
      that included stages mimicking peripheral auditory processing captured most of
      the data save for an overestimation of threshold ITDs obtained when the depth of
      modulation was 25% and the raised-sine exponent was 8.0. The purpose of the
      present study was: (1) to present a quantitative evaluation of how well other
      measures, including normalized envelope fourth moment, envelope peakwidth, and
      envelope "deadtime" might also account for the data reported by Bernstein and
      Trahiotis and (2) to present new threshold ITDs measured while varying,
      factorially, depth of modulation, raised-sine exponent, and modulation frequency.
      Quantitative analyses of both the prior and the new data showed that the
      normalized interaural correlation, computed subsequent to peripheral auditory
      processing, provided the most accurate predictions. Importantly, the
      overestimation of threshold ITDs did not occur when it was assumed that listeners
      can employ information within "off-frequency" auditory filters.

PMID- 20815459
TI  - Extracting binaural information from simultaneous targets and distractors:
      effects of amplitude modulation and asynchronous envelopes.
AB  - When different components of a stimulus carry different binaural information,
      processing of binaural information in a target component is often affected. The
      present experiments examine whether such interference is affected by amplitude
      modulation and the relative phase of modulation of the target and distractors. In
      all experiments, listeners attempted to discriminate interaural time differences
      of a target stimulus in the presence of distractor stimuli with ITD=0. In
      Experiment 1, modulation of the distractors but not the target reduced
      interference between components. In Experiment 2, synthesized musical notes
      exhibited little binaural interference when there were slight asynchronies
      between different streams of notes (31 or 62 ms). The remaining experiments
      suggested that the reduction in binaural interference in the previous experiments
      was due neither to the complex spectra of the synthesized notes nor to greater
      detectability of the target in the presence of modulated distractors. These data
      suggest that this interference is reduced when components are modulated in ways
      that result in the target appearing briefly in isolation, not because of
      segregation cues. These data also suggest that modulation and asynchronies
      between modulators that might be encountered in real-world listening situations
      are adequate to reduce binaural interference to inconsequential levels.

PMID- 20815460
TI  - Evaluation of feedback reduction techniques in hearing aids based on physical
      performance measures.
AB  - This paper presents a physical evaluation of four feedback cancellation
      techniques in commercial hearing aids and two implementations of a recently
      developed feedback cancellation algorithm. Based on physical measures for
      detecting instability, oscillations and distortion, three performance aspects
      were measured: 1) the added stable gain compared to the hearing aid operating
      without feedback reduction for white noise as well as for spectrally colored
      input signals in two static acoustic conditions, 2) the amount of feedback,
      oscillations and distortion at gain values below the maximum stable gain, 3) the
      ability to track feedback path changes. Added stable gains between 3 dB and 26 dB
      were identified. Five of the six techniques achieve worse feedback reduction for
      a tonal opera input signal than for a speech input signal. Preventing the
      feedback canceller to drift away from an initial feedback path measurement
      results in improved performance for tonal signals at the expense of a worse
      feedback reduction in the acoustic conditions that differ from the condition for
      which the initialization was performed, as well as a worse tracking of feedback
      path changes. Repeated measures indicated that the reproducibility of the test
      set-up is crucial, in particular when the hearing aid operates close to
      instability.

PMID- 20815461
TI  - Masking release and the contribution of obstruent consonants on speech
      recognition in noise by cochlear implant users.
AB  - Cochlear implant (CI) users are unable to receive masking release and the reasons
      are unclear. The present study examines the hypothesis that when listening to
      speech in fluctuating maskers, CI users cannot fuse the pieces of the message
      over temporal gaps because they are not able to perceive reliably the information
      carried by obstruent consonants (e.g., stops). To test this hypothesis, CI users
      were presented with sentences containing clean obstruent segments, but corrupted
      sonorant segments (e.g., vowels). Results indicated that CI users received
      masking release at low signal-to-noise ratio levels. Experiment 2 assessed the
      contribution of acoustic landmarks alone by presenting to CI users noise
      corrupted stimuli which had clearly marked vowel/consonant boundaries, but
      lacking clean obstruent consonant information. These stimuli were created using
      noise-corrupted envelopes processed using logarithmic compression during sonorant
      segments and a weakly-compressive mapping function during obstruent segments.
      Results indicated that the use of segment-dependent compression yielded
      significant improvements in intelligibility, but no masking release. The results
      from these experiments suggest that in order for CI users to receive masking
      release, it is necessary to perceive reliably not only the presence and location
      of acoustic landmarks (i.e., vowel/consonant boundaries) but also the information
      carried by obstruent consonants.

PMID- 20815462
TI  - Shifting fundamental frequency in simulated electric-acoustic listening.
AB  - Previous experiments have shown significant improvement in speech intelligibility
      under both simulated [Brown, C. A., and Bacon, S. P. (2009a). J. Acoust. Soc. Am.
      125, 1658-1665; Brown, C. A., and Bacon, S. P. (2010). Hear. Res. 266, 52-59] and
      real [Brown, C. A., and Bacon, S. P. (2009b). Ear Hear. 30, 489-493] electric
      acoustic stimulation when the target speech in the low-frequency region was
      replaced with a tone modulated in frequency to track the changes in the target
      talker's fundamental frequency (F0), and in amplitude with the amplitude envelope
      of the target speech. The present study examined the effects in simulation of
      applying these cues to a tone lower in frequency than the mean F0 of the target
      talker. Results showed that shifting the frequency of the tonal carrier downward
      by as much as 75 Hz had no negative impact on the benefit to intelligibility due
      to the tone, and that even a shift of 100 Hz resulted in a significant benefit
      over simulated electric-only stimulation when the sensation level of the tone was
      comparable to that of the tones shifted by lesser amounts.

PMID- 20815463
TI  - Effects of introducing low-frequency harmonics in the perception of vocoded
      telephone speech.
AB  - Several studies have demonstrated that telephone use presents a challenge for
      most cochlear implant (CI) users, and this is attributed mainly to the narrow
      bandwidth (300-3400 Hz) introduced by the telephone network. The present study
      focuses on answering the question whether telephone speech recognition in noise
      can be improved by introducing, prior to vocoder processing, low-frequency
      harmonic information encompassing the missing (due to the telephone network)
      information residing in the 0-300 Hz band. Experiment 1 regenerates the main
      harmonics and adjacent partials within the 0-600 Hz range in corrupted (by steady
      noise) telephone speech which has been vocoded to simulate electric-acoustic
      stimulation (EAS). Results indicated that introducing the main harmonics alone
      did not produce any benefits in intelligibility. Substantial benefit (20%) was
      observed, however, when both main harmonics and adjacent partials were
      regenerated in the acoustic portion of EAS-vocoded telephone speech. A similar
      benefit was noted in Experiment 2 when low-frequency harmonic information was
      introduced prior to processing noise-corrupted telephone speech using an eight
      channel vocoder. The gain in telephone speech intelligibility in noise obtained
      when low-frequency harmonic information was introduced can be attributed to the
      listeners having more reliable access to a combination of F0, glimpsing and
      lexical segmentation cues.

PMID- 20815464
TI  - Production of French vowels by American-English learners of French: language
      experience, consonantal context, and the perception-production relationship.
AB  - Second-language (L2) speech perception studies have demonstrated effects of
      language background and consonantal context on categorization and discrimination
      of vowels. The present study examined the effects of language experience and
      consonantal context on the production of Parisian French (PF) vowels by American
      English (AE) learners of French. Native AE speakers repeated PF vowels /i-y-u-oe
      a/ in bilabial /bVp/ and alveolar /dVt/ contexts embedded in the phrase /raCVCa/.
      Three AE groups participated: speakers without French experience (NoExp),
      speakers with formal French experience (ModExp), and speakers with formal-plus
      immersion experience (HiExp). Production accuracy was assessed by native PF
      listeners' judgments and by acoustic analysis. PF listeners identified L2
      learners' productions more accurately when the learners had extensive language
      experience, although /y-u-oe/ by even HiExp speakers were frequently
      misidentified. A consonantal context effect was evident, including /u/ produced
      by ModExp misidentified more often in alveolar context than in bilabial, and /y/
      misidentified more often in bilabial than in alveolar context, suggesting cross
      language transfer of coarticulatory rules. Overall, groups distinguished front
      rounded /y/ from /u/ in production, but often in a non-native manner, e.g.,
      producing /y/ as /(j)u/. Examination of perceptual data from the same individuals
      revealed a modest, yet complex, perception-production link for L2 vowels.

PMID- 20815465
TI  - Auditory feedback control of voice fundamental frequency in school children.
AB  - The present study was intended to address how the online control of voice
      fundamental frequency (F(0)) during vocalization develops from school children to
      young adults. Nineteen school children (7-12 years old) and twenty-one young
      adults (19-27 years old) participated in this experiment. They were asked to
      sustain a vowel sound /u/ while their voice pitch feedback was randomly shifted
      (+/-50, +/-100, +/-200, and +/-500 cents) and fed back to them instantaneously
      over headphones. Results showed that school children produced significantly
      larger but slower compensatory responses to voice pitch feedback perturbations
      than young adults. Response latencies became longer with the increase in pitch
      perturbation magnitude, but no systematic changes were found as a function of
      stimulus direction. In addition, the number of responses "following" the stimulus
      direction across different stimulus magnitudes for school children was greater
      than for young adults. These findings demonstrate developmental changes of vocal
      responses to pitch feedback perturbations during vocalization from school
      children to young adults, and suggest that vocal responses can serve as an
      objective index of the maturation of the audio-vocal system.

PMID- 20815466
TI  - Phonetic tone signals phonological quantity and word structure.
AB  - Many languages exploit suprasegmental devices in signaling word meaning. Tone
      languages exploit fundamental frequency whereas quantity languages rely on
      segmental durations to distinguish otherwise similar words. Traditionally,
      duration and tone have been taken as mutually exclusive. However, some evidence
      suggests that, in addition to durational cues, phonological quantity is
      associated with and co-signaled by changes in fundamental frequency in quantity
      languages such as Finnish, Estonian, and Serbo-Croat. The results from the
      present experiment show that the structure of disyllabic word stems in Finnish
      are indeed signaled tonally and that the phonological length of the stressed
      syllable is further tonally distinguished within the disyllabic sequence. The
      results further indicate that the observed association of tone and duration in
      perception is systematically exploited in speech production in Finnish.

PMID- 20815467
TI  - Beyond arousal: valence and potency/control cues in the vocal expression of
      emotion.
AB  - The important role of arousal in determining vocal parameters in the expression
      of emotion is well established. There is less evidence for the contribution of
      emotion dimensions such as valence and potency/control to vocal emotion
      expression. Here, an acoustic analysis of the newly developed Geneva Multimodal
      Emotional Portrayals corpus, is presented to examine the role of dimensions other
      than arousal. This corpus contains twelve emotions that systematically vary with
      respect to valence, arousal, and potency/control. The emotions were portrayed by
      professional actors coached by a stage director. The extracted acoustic
      parameters were first compared with those obtained from a similar corpus [Banse
      and Scherer (1996). J. Pers. Soc. Psychol. 70, 614-636] and shown to largely
      replicate the earlier findings. Based on a principal component analysis, seven
      composite scores were calculated and were used to determine the relative
      contribution of the respective vocal parameters to the emotional dimensions
      arousal, valence, and potency/control. The results show that although arousal
      dominates for many vocal parameters, it is possible to identify parameters, in
      particular spectral balance and spectral noise, that are specifically related to
      valence and potency/control.

PMID- 20815468
TI  - Prosodic predictors of upcoming positive or negative content in spoken messages.
AB  - This article examines potential prosodic predictors of emotional speech in
      utterances perceived as conveying that good or bad news is about to be delivered.
      Speakers were asked to call an experimental confederate to inform her about
      whether or not she had been given a job she had applied for. A perception study
      was then performed in which initial fragments of the recorded utterances, not
      containing any explicit lexical cues to emotional content, were presented to
      listeners who had to rate whether good or bad news would follow the utterance.
      The utterances were then examined to discover acoustic and prosodic features that
      distinguished between good and bad news. It was found that speakers in the
      production study were not simply reflecting their own positive or negative mood
      during the experiment, but rather appeared to be influenced by the valence of the
      positive or negative message they were preparing to deliver. Positive and
      negative utterances appeared to be judged differently with respect to a number of
      perceived attributes of the speakers' voices (like sounding hesitant or nervous).
      These attributes correlated with a number of automatically obtained acoustic
      features.

PMID- 20815469
TI  - Language-specific realizations of syllable structure and vowel-to-vowel
      coarticulation.
AB  - This paper investigates the effects of syllable structure on vowel-to-vowel (V-to
      V) coarticulation using Thai and English data. Languages differ in syllable
      complexity and their realizations of syllable structure. It was hypothesized that
      languages with complex syllable structure (English) would allow more V-to-V
      coarticulation than languages with simple syllable structure (Thai). Onset and
      coda consonants are different acoustically, articulatorily, typologically and
      perceptually. Onsets are generally 'stronger' and more stable than codas because
      they are longer, louder, and involve tighter articulatory constrictions. It was
      hypothesized that closed syllables (that end in a consonant C, i.e., VC#V) would
      allow more V-to-V coarticulation than open syllables (V#CV). /C(1)V(1)#C(2)V(2)/
      and /C(1)V(1)C(2)#V(2)t/ sequences were recorded from six native speakers in Thai
      and six in English. First and second formant frequencies were measured. Results
      show that English allows more V-to-V coarticulation than Thai regardless of the
      intervocalic duration and vowel quality difference, but open and closed syllables
      only affect V-to-V coarticulation minimally. In addition to syllable structure,
      other possible factors contributing to the language difference in V-to-V
      coarticulation are discussed.

PMID- 20815470
TI  - Talker-listener accent interactions in speech-in-noise recognition: effects of
      prosodic manipulation as a function of language experience.
AB  - Previous work has shown that accents affect speech recognition accuracy in noise,
      with intelligibility being modulated by the similarity between the talkers' and
      listeners' accents, particularly in the case where they have different L1s. The
      present study examined the contribution of prosody to recognizing native (L1) and
      non-native (L2) speech in noise, and how this is affected by the listener's L2
      experience. A group of monolingual English listeners and two groups of French
      listeners with varying L2 English experience were presented with English
      sentences produced by L1 and L2 (French) speakers. The stimuli were digitally
      processed to exchange the pitch and segment durations between recordings of the
      same sentences produced by different speakers (e.g., imposing a French-accented
      prosody onto recordings made from English speakers). The results revealed that
      English listeners were more accurate at recognizing L1 English with English
      prosody, the French inexperienced listeners were more accurate at recognizing
      French-accented speech with French prosody, and the French experienced listeners
      varied in the cues that they used depending on the noise level, showing more
      flexibility of processing. The use of prosodic cues in noise thus appears to be
      modulated by language experience and varies according to listening context.

PMID- 20815471
TI  - Acoustic fidelity of internet bandwidths for measures used in speech and voice
      disorders.
AB  - The purpose of this study was to explore the impact of different bandwidths on
      acoustic measures when using low-cost internet technology of teletherapy in the
      field of speech and language rehabilitation. Normal speech and voice samples were
      collected at a clinic and a remote place by connecting the computers to Skype and
      VoiceEmotion software, while the disordered speech samples were collected through
      teaching CD samples from a quality voice textbook. Pure tones at 200 and 1000 Hz
      were also collected. The acoustic parameters: average fundamental frequency (F0),
      jitter percent, shimmer percent and noise-to-harmonic ratio (NHR) were used for
      fidelity analysis. The average F0 increased across all samples and bandwidths.
      There was greater increase and variability on the disordered voice samples.
      Speaking F0 was shown to both increase and decrease in no identifiable pattern
      with the different bandwidths. Jitter, shimmer and NHR were significantly
      different on pre- and post-transmission trials. The study provided preliminary
      pilot data on the fidelity effect of internet transmission on acoustic variables
      for voice and speech. Cautious suggestions were also provided to speech and
      language therapists who would consider using teletherapy for speech and voice
      diagnosis and treatment.

PMID- 20815472
TI  - Analyzing phonetic confusions using formal concept analysis.
AB  - Confusion matrices have been used as a tool for the analysis of speech perception
      or human speech recognition (HSR) for decades. However, they are rarely employed
      in automatic speech recognition (ASR) mainly due to the lack of a systematic
      procedure for their exploration. The generalization of formal concept analysis
      employed in this paper provides a conceptual interpretation of confusion matrices
      that enables the analysis of the structure of confusions for both human and
      machine performances. Generalized formal concept analysis transforms confusion
      matrices into ordered lattices of confusion events, supporting classic results in
      HSR that identify a hierarchy of virtual articulatory-acoustic channels.
      Translating this technique into ASR, a detailed map of the relationships among
      the speech units employed in the system can be traced to make different sources
      of confusions apparent: the influence of the lexicon, segmentation errors,
      dialectal variations or limitations of the feature extraction procedures, among
      others.

PMID- 20815473
TI  - A hybrid scheme for bore design optimization of a brass instrument.
AB  - This paper presents how the shape of a brass instrument can be optimized with
      respect to its intonation properties. The instrument is modeled using a hybrid
      method between a lossy one-dimensional transmission line analogy for the slowly
      flaring part of the instrument, and a two-dimensional finite element model for
      the rapidly flaring part. The optimization employs gradient-based algorithms, and
      allows for a large number of design variables. Through the use of an appropriate
      choice of design variables, the algorithm is capable of rapidly finding horn
      profiles that are optimal subject to various geometric constraints, such as
      increasing or convex bell flares. It is found that under a convexity constraint,
      brass wind bells that are optimal with respect to an intonation condition can be
      constructed of piecewise conical sections.

PMID- 20815474
TI  - The psychomechanics of simulated sound sources: material properties of impacted
      thin plates.
AB  - Sounds convey information about the materials composing an object. Stimuli were
      synthesized using a computer model of impacted plates that varied their material
      properties: viscoelastic and thermoelastic damping and wave velocity (related to
      elasticity and mass density). The range of damping properties represented a
      continuum between materials with predominant viscoelastic and thermoelastic
      damping (glass and aluminum, respectively). The perceptual structure of the
      sounds was inferred from multidimensional scaling of dissimilarity judgments and
      from their categorization as glass or aluminum. Dissimilarity ratings revealed
      dimensions that were closely related to mechanical properties: a wave-velocity
      related dimension associated with pitch and a damping-related dimension
      associated with timbre and duration. When asked to categorize sounds, however,
      listeners ignored the cues related to wave velocity and focused on cues related
      to damping. In both dissimilarity-rating and identification experiments, the
      results were independent of the material of the mallet striking the plate (rubber
      or wood). Listeners thus appear to select acoustical information that is reliable
      for a given perceptual task. Because the frequency changes responsible for
      detecting changes in wave velocity can also be due to changes in geometry, they
      are not as reliable for material identification as are damping cues.

PMID- 20815475
TI  - Numerical analysis of biosonar beamforming mechanisms and strategies in bats.
AB  - Beamforming is critical to the function of most sonar systems. The conspicuous
      noseleaf and pinna shapes in bats suggest that beamforming mechanisms based on
      diffraction of the outgoing and incoming ultrasonic waves play a major role in
      bat biosonar. Numerical methods can be used to investigate the relationships
      between baffle geometry, acoustic mechanisms, and resulting beampatterns. Key
      advantages of numerical approaches are: efficient, high-resolution estimation of
      beampatterns, spatially dense predictions of near-field amplitudes, and the
      malleability of the underlying shape representations. A numerical approach that
      combines near-field predictions based on a finite-element formulation for
      harmonic solutions to the Helmholtz equation with a free-field projection based
      on the Kirchhoff integral to obtain estimates of the far-field beampattern is
      reviewed. This method has been used to predict physical beamforming mechanisms
      such as frequency-dependent beamforming with half-open resonance cavities in the
      noseleaf of horseshoe bats and beam narrowing through extension of the pinna
      aperture with skin folds in false vampire bats. The fine structure of biosonar
      beampatterns is discussed for the case of the Chinese noctule and methods for
      assessing the spatial information conveyed by beampatterns are demonstrated for
      the brown long-eared bat.

PMID- 20815476
TI  - The acoustic field on the forehead of echolocating Atlantic bottlenose dolphins
      (Tursiops truncatus).
AB  - Arrays of up to six broadband suction cup hydrophones were placed on the forehead
      of two bottlenose dolphins to determine the location where the beam axis emerges
      and to examine how signals in the acoustic near-field relate to signals in the
      far-field. Four different array geometries were used; a linear one with
      hydrophones arranged along the midline of the forehead, and two around the front
      of the melon at 1.4 and 4.2 cm above the rostrum insertion, and one across the
      melon in certain locations not measured by other configurations. The beam axis
      was found to be close to the midline of the melon, approximately 5.4 cm above the
      rostrum insert for both animals. The signal path coincided with the low-density,
      low-velocity core of the melon; however, the data suggest that the signals are
      focused mainly by the air sacs. Slight asymmetry in the signals were found with
      higher amplitudes on the right side of the forehead. Although the signal waveform
      measured on the melon appeared distorted, when they are mathematically summed in
      the far-field, taking into account the relative time of arrival of the signals,
      the resultant waveform matched that measured by the hydrophone located at 1 m.

PMID- 20815477
TI  - Density estimation of Yangtze finless porpoises using passive acoustic sensors
      and automated click train detection.
AB  - A method is presented to estimate the density of finless porpoises using
      stationed passive acoustic monitoring. The number of click trains detected by
      stereo acoustic data loggers (A-tag) was converted to an estimate of the density
      of porpoises. First, an automated off-line filter was developed to detect a click
      train among noise, and the detection and false-alarm rates were calculated.
      Second, a density estimation model was proposed. The cue-production rate was
      measured by biologging experiments. The probability of detecting a cue and the
      area size were calculated from the source level, beam patterns, and a sound
      propagation model. The effect of group size on the cue-detection rate was
      examined. Third, the proposed model was applied to estimate the density of
      finless porpoises at four locations from the Yangtze River to the inside of
      Poyang Lake. The estimated mean density of porpoises in a day decreased from the
      main stream to the lake. Long-term monitoring during 466 days from June 2007 to
      May 2009 showed variation in the density 0-4.79. However, the density was fewer
      than 1 porpoise/km(2) during 94% of the period. These results suggest a potential
      gap and seasonal migration of the population in the bottleneck of Poyang Lake.

PMID- 20815478
TI  - Experience-dependent development of vocalization selectivity in the auditory
      cortex.
AB  - Vocalization-selective neurons are present in the auditory systems of several
      vertebrate groups. Vocalization selectivity is influenced by developmental
      experience, but the underlying mechanisms are only beginning to be understood.
      Evidence is presented in this review for the hypothesis that plasticity of timing
      and strength of inhibition is a mechanism for plasticity of vocalization
      selectivity. The pallid bat echolocates using downward frequency modulated (FM)
      sweeps. Nearly 70% of neurons with tuning in the echolocation frequency range in
      its auditory cortex respond selectively to the direction and rate of change of
      frequencies present in the echolocation call. During development, FM rate
      selectivity matures early, while direction selectivity emerges later. Based on
      the time course of development it was hypothesized that FM direction, but not
      rate, selectivity is experience-dependent. This hypothesis was tested by altering
      echolocation experience during development. The results show that normal
      echolocation experience is required for both refinement and maintenance of
      direction selectivity. Interestingly, experience is required for the maintenance
      of rate selectivity, but not for initial development. Across all ages and
      experimental groups, the timing relationship between inhibitory and excitatory
      inputs explains sweep selectivity. These experiments suggest that inhibitory
      plasticity is a substrate for experience-dependent changes in vocalization
      selectivity.

PMID- 20815479
TI  - Frequency tuning and latency organization of responses in the inferior colliculus
      of Japanese house bat, Pipistrellus abramus.
AB  - Pipistrellus abramus emits quasi-constant frequency pulses during search, which
      extend the end frequency portion of the downward frequency-modulated sweep
      (terminal frequency; TF). If the narrowed frequency range is important for
      detecting a small frequency change caused by insect fluttering, the bats may need
      much finer frequency resolution at the TF. To test this hypothesis, the
      distribution of the best frequencies (BFs) in the inferior colliculus (IC) was
      electrophysiologically measured. The TF of the echolocation pulse was 41.44+/
      2.62 kHz. The frequency range of 35-45 kHz was overrepresented in the IC
      (n=50/105; 48%), and a faint second peak was seen at 75-85 kHz (the second
      harmonic of the TF) in the BF distribution. The BF increased as a function of
      recording depth along the dorsoventral axis, except for the BFs of 35-45 and 75
      85 kHz, which were found at a wide range of depths. The response latency ranged
      between 3.7 and 23.2 ms for the BFs of 35-45 kHz, and the maximum target range
      was estimated to be 3.3 m from the delay line observed in the IC. These
      electrophysiological measures suggest the importance of a target distance within
      approximately 3 m, which is consistent with behavioral measures during foraging
      in this species.

PMID- 20815480
TI  - Relationship of blood flow and metabolism to acoustic processing centers of the
      dolphin brain.
AB  - Odontocete brain tissues associated with auditory processing are hypertrophied
      and modified relative to their terrestrial counterparts. The relationship between
      the functional demand on these tissues and metabolic substrate requirements is
      unknown. Using positron emission tomography (PET), relative cerebral blood flow
      was measured in a bottlenose dolphin. Approximately 60 mCi (13)NH(3) was
      administered to the dolphin via a catheter inserted into the hepatic vein and
      threaded proximate to the vena cava. Radiolabel initially appeared as distributed
      focal points in the cerebellum. Increasing scan time resulted in an increase in
      the number of focal regions and in the diffusivity of label activity throughout
      the brain. The time course and spatial distribution of radiolabel was consistent
      with a cerebral blood supply dominated by the spinal meningeal arteries. Blood
      flow was predominantly observed in the cerebellum and neocortex, particularly the
      auditory and visual cortex. Differential brain glucose uptake, previously
      measured in a separate dolphin, showed good agreement with the differential
      supply of blood to brain tissues. Rates of blood supply and glucose uptake in the
      auditory cortex, inferior colliculus, and cerebellum are consistent with a high
      metabolic demand of tissues which are important to the integration of auditory
      and other sensory inputs.

PMID- 20815481
TI  - Sonar detection of jittering real targets in a free-flying bat.
AB  - The auditory system measures time with exceptional precision. Echolocating bats
      evaluate the time delay between call and echo to measure object range. An extreme
      and disputed result on ranging acuity was found in the virtual delay jitter
      experiments. In these studies, echoes with alternating delays were played back to
      bats, which detected a jitter down to 10 ns, corresponding to a ranging acuity of
      1.7 microm. The current study was designed to measure the ranging acuity of the
      nectarivorous bat Glossophaga soricina under semi-natural conditions. Three free
      flying bats were trained to discriminate between a stationary loudspeaker
      membrane and a membrane sinusoidally vibrating at 10 Hz. At detection threshold,
      the average peak-to-peak displacement of the vibrating membrane was 13 mm,
      corresponding to an echo delay jitter of 75 micros. The perceived jitter from
      call to call, which depends on the pulse interval and the call emission time
      relative to the membrane phase, was simulated for comparison with the virtual
      jitter experiments. This call-to-call jitter was between 20 to 25 micros (ca. 4
      mm ranging acuity). These thresholds between 20 and 75 micros (4-13 mm) fall
      within both ecologically and physiologically plausible ranges, allowing for
      sufficiently precise navigation and foraging.

PMID- 20815482
TI  - Widespread passive acoustic detection of Yangtze finless porpoise using miniature
      stereo acoustic data-loggers: a review.
AB  - Data on distribution, abundance, ecology, and behavior are essential for
      conservation and management of endangered animals in the wild. Yangtze finless
      porpoise (Neophocaena phocaenoides asiaeorientalis) is an endangered small
      odontocete species, living exclusively in the Yangtze River and its connecting
      Poyang and Dongting Lakes. Frequent production of high-frequency bio-sonar
      signals allows the animal to be detectable using passive acoustic methods.
      Recently, a stereo acoustic event data-logger (A-tag) has been used extensively
      to detect the animal by using both fixed and mobile platforms. The passive
      acoustic monitoring methods were not only successful in detecting the presence of
      animals, but also in counting, localizing, and tracking phonating individuals.
      Underwater behavior observed acoustically helped to assess possible effects of
      vessels on the animals during acoustic surveys.

PMID- 20815483
TI  - A method to enable a bottlenose dolphin (Tursiops truncatus) to echolocate while
      out of water.
AB  - The study of site-specific brain activity associated with dolphin echolocation
      has been hampered by the difficulties inherent in administering radiolabels and
      performing medical imaging while a dolphin echolocates in an aquatic environment.
      To overcome these limitations, a system has been developed to allow a bottlenose
      dolphin to echolocate while out of the water. The system relies on a "phantom
      echo generator" (PEG) consisting of a Texas Instruments C6713 digital signal
      processor with an analog input/output daughtercard. Echolocation clicks produced
      by the dolphin are detected with a hydrophone embedded in a suction cup on the
      melon, then digitized within the PEG. Clicks exceeding a user-defined threshold
      are convolved with a target impulse response, delayed, and scaled before being
      converted to analog and transmitted through a sound projector embedded in a
      suction cup attached to the dolphin's lower jaw. Dolphin in-air echolocation
      behavior, inter-click intervals, and overall performance were analogous to those
      observed during comparable underwater testing with physical targets,
      demonstrating that the dolphin was indeed performing an echolocation task while
      out of water.

PMID- 20815484
TI  - Pattern-matching analysis of fine echo delays by the spectrogram correlation and
      transformation receiver.
AB  - Among a few previous attempts to model the outstanding echolocation capability of
      bats, the work by Saillant et al. [J. Acoust. Soc. Am. 94, 2691-2712 (1993)] is,
      arguably, one of the most frequently referenced studies in which the predictions
      of spectrogram correlation and transformation (SCAT) model were compared to the
      results of relevant behavioral experiments. The SCAT model consists of cochlear,
      spectrogram correlation and spectrogram transformation blocks, where the latter
      two processes estimate the overall and the fine time delays between the animal's
      call and the echoes, given the neural representation of the acoustic signals
      generated by the cochlear block. This paper first provides a rigorous account of
      the spectrogram transformation (ST) block. By approximating the neural signals in
      analytic forms, many aspects of the ST block are explained and discussed in
      relation to the predictive scope of the model. Furthermore, based on these
      analytical arguments, the ST block is investigated from a different point of
      view, interpreted as a pattern-matching process which may operate at the high
      level of the animal's auditory pathway.

PMID- 20815485
TI  - Stereotypic vocalizations in harvest mice (Reithrodontomys): Harmonic structure
      contains prominent and distinctive audible, ultrasonic, and non-linear elements.
AB  - Reports of audible vocalizations are rare in adult muroid rodents, animals
      generally very small in body size and under strong predation pressure. By
      contrast, communication using high, often ultrasonic vocal frequencies is
      relatively common. There are anecdotal reports of audible vocalizations for some
      harvest mice (genus Reithrodontomys), however none have been recorded or
      analyzed. Several species of harvest mice are studied, representing the subgenera
      Reithrodontomys (R. fulvescens, R. sumichrasti) and Aporodon (R. creper, R.
      mexicanus, R. spp.), as part of a larger phylogenetic analysis of stereotypical
      vocal communication. Only R. mexicanus produced stereotyped vocalizations on a
      regular basis. Acoustic signals of R. mexicanus contain prominent harmonics
      bridging both the audible and ultrasonic range, with evidence of non-linear
      distribution of energy within and between notes of an individual call. Harmonic
      emphasis varies, making the carrier frequency difficult to locate. These
      Reithrodontomys vocalizations are compared with members of their phylogenetic
      sister group Onychomys+Peromyscus, genera whose stereotypic calls exclusively
      occupy the audible or ultrasonic spectrum, respectively. It is hypothesized that
      the stereotypic signals of harvest mice represent announcement calls. Given the
      number of anecdotal reports of stereotyped 1, 2, and 3-note calls among
      Reithrodontomys species, further interspecific comparisons are warranted.

PMID- 20815550
TI  - Communication: Mass-analyzed velocity map imaging of thermal photofragments from
      C60.
AB  - The velocity distributions of the fragments produced by dissociative
      photoionization of C(60) have been measured in the extreme UV region for the
      first time, by using a flight-time resolved velocity map imaging technique
      combined with a high-temperature molecular beam and synchrotron radiation. Values
      of the average kinetic energy release were estimated at six different photon
      energies with respect to five reaction steps of sequential C(2) ejection,
      starting from C(60)(2+)-->C(58)(2+)+C(2) to C(52)(2+)-->C(50)(2+)+C(2). The
      translational temperatures of the fragment ions were found to be lower than those
      obtained by laser multiphoton absorption of C(60). The kinetic energies released
      in the first to fourth steps increase with increasing hnu and reach 0.35-0.5 eV
      at hnu=102 eV, reflecting statistical redistribution of the excess energy in the
      transition state, whereas that in the fifth step leading to C(50)(2+) was
      exceptionally small.

PMID- 20815486
TI  - A model for the dynamics of ultrasound contrast agents in vivo.
AB  - The Rayleigh-Plesset (RP) equation for a clean gas bubble in an incompressible
      and infinite liquid has previously been applied to approximately simulate the
      behavior of ultrasound contrast agents (UCA) in vivo, and extended RP equations
      have been proposed to account for the effects of the UCA shell or surrounding
      soft tissue. These models produce results that are consistent with experimental
      measurements for low acoustic pressure scenarios. For applications of UCAs in
      therapeutic medicine, the transmitted acoustic pulse can have a peak negative
      pressure (PNP) up to a few megapascals, resulting in discrepancies between
      measurements and predictions using these extended RP equations. Here, a model was
      developed to describe the dynamics of UCAs in vivo while taking account of the
      effects of liquid compressibility, the shell and the surrounding tissue. Liquid
      compressibility is approximated to first order and the shell is treated either as
      a Voigt viscoelastic solid or a Newtonian viscous liquid. Finite deformation of
      the shell and tissue is derived. Dynamics of UCAs with a shell of lipid, polymer,
      albumin and liquid are investigated for typical therapeutic ultrasound pulses.
      The effects of liquid compressibility and shell and tissue parameters are
      analyzed.

PMID- 20815551
TI  - Communication: Mode-selective vibrational excitation induced by nonequilibrium
      transport processes in single-molecule junctions.
AB  - In a nanoscale molecular junction at finite bias voltage, the intramolecular
      distribution of vibrational energy can strongly deviate from the thermal
      equilibrium distribution and specific vibrational modes can be selectively
      excited in a controllable way, regardless of the corresponding mode frequency.
      This is demonstrated for generic models of asymmetric molecular junctions with
      localized electronic states, employing a master equation as well as a
      nonequilibrium Green's function approach. It is shown that the applied bias
      voltage controls the excitation of specific vibrational modes by tuning the
      efficiency of vibrational cooling processes due to energy exchange with the
      leads.

PMID- 20815552
TI  - Communication: Feshbach resonances in the water molecule revealed by state
      selective spectroscopy.
AB  - We employ triple-resonance vibrational overtone excitation to access quasibound
      states of water from several fully characterized bound states of the molecule.
      Comparison of the measured dissociation spectra allows a rigorous assignment of
      rotational quantum numbers J, nuclear spin and parity, and a tentative
      vibrational characterization of the observed resonances. Their asymmetrical
      shapes (Fano profiles) reflect interference of dipole moments for transitions to
      these resonances with that to the dissociative continuum. The assignments and
      Fano profile parameters of the resonances stand as a benchmark for the extension
      of accurate quantum-mechanical calculations to activated complexes of water. The
      narrow widths of some of these resonances indicate that water molecules may
      survive for as long as up to 60 ps in states above the dissociation threshold. We
      consider the possible implication of such long-lived states for the kinetics of
      water dissociation and the OH+H association reaction.

PMID- 20815553
TI  - Communication: An extended model of liquid bridging.
AB  - Recent phenomenological studies have drawn attention to an appealing effect,
      observed for the first time in 1893, today known as water-bridge. The phenomenon
      has been ascribed to unknown properties of water. We report some experimental
      results showing that, contrary to a widely common belief, the phenomenon is not
      to be related with water neither with a property of hydrogen bonded networks.
      Using a very simple model, we show that the liquid bridge phenomenon is
      originated by electrostatic effects and can be reproduced in any dense fluid with
      no respect of its peculiar molecular properties. This basic approach is able to
      reproduce many of the experimentally observed features of the bridge formation.
      In perspective of future investigations, the possible phenomena responsible of
      the bridge stability, after its formation, are briefly discussed.

PMID- 20815554
TI  - Mimicking coarse-grained simulations without coarse-graining: enhanced sampling
      by damping short-range interactions.
AB  - The damped-short-range-interaction (DSRI) method is proposed to mimic coarse
      grained simulations by propagating an atomistic scale system on a smoothed
      potential energy surface. The DSRI method has the benefit of enhanced sampling
      provided by a typical coarse-grained simulation without the need to perform
      coarse-graining. Our method was used to simulate liquid water, alanine dipeptide
      folding, and the self-assembly of dimyristoylphosphatidylcholine lipid. In each
      case, our method appreciably accelerated the dynamics without significantly
      changing the free energy surface. Additional insights from DSRI simulations and
      the promise of coupling our DSRI method with Hamiltonian replica-exchange
      molecular dynamics are discussed.

PMID- 20815555
TI  - Time-dependent auxiliary density perturbation theory.
AB  - The recently developed auxiliary density perturbation theory is extended to time
      dependent perturbations. As its static counterpart, it is based on auxiliary
      density functional theory in which the Coulomb and exchange-correlation
      potentials are expressed through one auxiliary function density. As in the case
      of static perturbations a noniterative alternative to the corresponding coupled
      perturbed Kohn-Sham method is formulated. The new methodology is validated by
      local and gradient corrected dynamical polarizability calculations. Comparison
      with experiment indicates that for low frequencies reliable dynamical
      polarizabilities are obtained. Our discussion also shows that the computational
      performance of time-dependent auxiliary density perturbation theory is similar to
      the previously described static approach. In order to demonstrate the potential
      of this new methodology, dynamic polarizabilities of C(60), C(180), and C(240)
      are calculated.

PMID- 20815556
TI  - Exact nonadditive kinetic potentials for embedded density functional theory.
AB  - We describe an embedded density functional theory (DFT) protocol in which the
      nonadditive kinetic energy component of the embedding potential is treated
      exactly. At each iteration of the Kohn-Sham equations for constrained electron
      density, the Zhao-Morrison-Parr constrained search method for constructing Kohn
      Sham orbitals is combined with the King-Handy expression for the exact kinetic
      potential. We use this formally exact embedding protocol to calculate ionization
      energies for a series of three- and four-electron atomic systems, and the results
      are compared to embedded DFT calculations that utilize the Thomas-Fermi (TF) and
      the Thomas-Fermi-von Weisacker approximations to the kinetic energy functional.
      These calculations illustrate the expected breakdown due to the TF approximation
      for the nonadditive kinetic potential, with errors of 30%-80% in the calculated
      ionization energies; by contrast, the exact protocol is found to be accurate and
      stable. To significantly improve the convergence of the new protocol, we
      introduce a density-based switching function to map between the exact nonadditive
      kinetic potential and the TF approximation in the region of the nuclear cusp, and
      we demonstrate that this approximation has little effect on the accuracy of the
      calculated ionization energies. Finally, we describe possible extensions of the
      exact protocol to perform accurate embedded DFT calculations in large systems
      with strongly overlapping subsystem densities.

PMID- 20815557
TI  - Alchemical derivatives of reaction energetics.
AB  - Based on molecular grand canonical ensemble density functional theory, we present
      a theoretical description of how reaction barriers and enthalpies change as atoms
      in the system are subjected to alchemical transformations, from one element into
      another. The change in the energy barrier for the umbrella inversion of ammonia
      is calculated along an alchemical path in which the molecule is transformed into
      water, and the change in the enthalpy of protonation for methane is calculated as
      the molecule is transformed into a neon atom via ammonia, water, and hydrogen
      fluoride. Alchemical derivatives are calculated analytically from the
      electrostatic potential in the unperturbed system, and compared to numerical
      derivatives calculated with finite difference interpolation of the
      pseudopotentials for the atoms being transformed. Good agreement is found between
      the analytical and numerical derivatives. Alchemical derivatives are also shown
      to be predictive for integer changes in atomic numbers for oxygen binding to a 79
      atom palladium nanoparticle, illustrating their potential use in gradient-based
      optimization algorithms for the rational design of catalysts.

PMID- 20815558
TI  - Molecular dynamics simulation with weak coupling to heat and material baths.
AB  - A method for performing molecular dynamics simulation in the grand canonical
      ensemble is developed. The molecular dynamics, with coupling to an external bath,
      simulation method of [Berendsen et al., J. Chem. Phys. 81, 3684 (1984)] is
      extended for this purpose. Here the physical system of interest consists of real
      indistinguishable particles plus one fractional particle, whose potential energy
      of interaction with the rest of particles is scaled by a coupling parameter,
      ranging dynamically between zero and one. This coupling changes the number of
      particles in the system gradually and dynamically, depending on the target values
      of the excess chemical potential, temperature, and volume. A nonlinear scaling
      scheme has been adopted to scale the potential energy of interaction of the
      fractional particle with the rest of the system. The method has been employed to
      predict the density of compressed Lennard-Jones fluid, compatible with the target
      values of temperature and the excess chemical potential, over a wide range of
      temperatures and densities. The method has further been applied to do molecular
      dynamics simulation in the grand canonical ensemble for water and to predict its
      vapor-liquid phase coexistence point. The results obtained using this method are
      in complete agreement with previously reported results in the literature.

PMID- 20815559
TI  - Vapor-liquid nucleation of argon: exploration of various intermolecular
      potentials.
AB  - The homogeneous vapor-liquid nucleation of argon has been explored at T=70 and 90
      K using classical nucleation theory, semiempirical density functional theory, and
      Monte Carlo simulations using the aggregation-volume-bias algorithm with umbrella
      sampling and histogram-reweighting. In contrast with previous simulation studies,
      which employed only the Lennard-Jones intermolecular potential, the current
      studies were carried out using various pair potentials including the Lennard
      Jones potential, a modified Buckingham exponential-six potential, the Barker
      Fisher-Watts pair potential, and a recent ab initio potential developed using the
      method of effective diameters. It was found that the differences in the free
      energy of formation of the critical nuclei between the potentials cannot be
      explained solely in terms of the difference in macroscopic properties of the
      potentials, which gives a possible reason for the failure of classical nucleation
      theory.

PMID- 20815560
TI  - Renner-Teller intersections along the collinear axes of polyatomic molecules:
      H2CN as a case study.
AB  - The tetra-atomic C(2)H(2)(+) cation is known to form Renner-Teller-type
      intersections along its collinear axis. Not too long ago, we studied the
      nonadiabatic coupling terms (NACTs) of this molecule [G. J. Halasz et al., J.
      Chem. Phys. 126, 154309 (2007)] and revealed two kinds of intersections. (i) By
      employing one of the hydrogens as a test particle, we revealed the fact that
      indeed the corresponding (angular) NACTs produce topological (Berry) phases that
      are equal to 2pi, which is a result anticipated in the case of Renner-Teller
      intersections. (ii) However, to our big surprise, repeating this study when one
      of the atoms (in this case a hydrogen) is shifted from the collinear arrangement
      yields for the corresponding topological phase a value that equals pi (and not
      2pi). In other words, shifting (even slightly) one of the atoms from the
      collinear arrangement causes the intersection to change its character and become
      a Jahn-Teller intersection. This somewhat unexpected novel result was later
      further analyzed and confirmed by other groups [e.g., T. Vertesi and R. Englman,
      J. Phys. B 41, 025102 (2008)]. The present article is devoted to another tetra
      atomic molecule, namely, the H(2)CN molecule, which just like the C(2)H(2)(+)
      ion, is characterized by Renner-Teller intersections along its collinear axis.
      Indeed, we revealed the existence of Renner-Teller intersections along the
      collinear axis, but in contrast to the C(2)H(2)(+) case a shift of one atom from
      the collinear arrangement did not form Jahn-Teller intersections. What we found
      instead is that the noncollinear molecule was not affected by the shift and kept
      its Renner-Teller character. Another issue treated in this article is the
      extension of (the two-state) Berry (topological) phase to situations with
      numerous strongly interacting states. So far the relevance of the Berry phase was
      tested for systems characterized by two isolated interacting states, although it
      is defined for any number of interacting states [M. V. Berry, Proc. R. Soc.
      London, Ser. A 392, 45 (1984)]. We intend to show how to overcome this limitation
      and get a valid, fully justified definition of a Berry phase for an isolated
      system of any number of interacting states (as is expected).

PMID- 20815561
TI  - Global and local Voronoi analysis of solvation shells of proteins.
AB  - This paper presents the structure and dynamics of hydration shells for the three
      proteins: ubiquitin, calbindin, and phospholipase. The raw data derived from
      molecular dynamics simulations are analyzed on the basis of fully atomistic
      Delaunay tesselations. In order to cope with the high numerical effort for the
      computation of these Voronoi shells, we have implemented and optimized an
      intrinsically periodic algorithm. Based on this highly efficient Voronoi
      decomposition, a variety of properties is presented: three dimensional water and
      ion nuclear densities as well as the geometrical packing of water molecules are
      discussed. Thereby, we develop Voronoi interface surface area, the Voronoi analog
      of the well known solvent accessible surface area. The traditional radial
      distribution functions are resolved into Voronoi shells as a transient device to
      the new concept of shell-grained orientational order. Thus, we analyze the donor
      acceptor property as well as the amount of dielectric screening. Shell dynamics
      is described in terms of mean residence times. In this way, a retardation factor
      for different shells can be derived and was compared to experimental values. All
      these results and properties are presented both at the global protein level as
      well as at the local residue level.

PMID- 20815562
TI  - Dynamical effects in ab initio NMR calculations: classical force fields fitted to
      quantum forces.
AB  - NMR chemical shifts for an L-alanine molecular crystal are calculated using ab
      initio plane wave density functional theory. Dynamical effects including
      anharmonicity may be included by averaging chemical shifts over an ensemble of
      structural configurations generated using molecular dynamics (MD). The time
      scales required mean that ab initio MD is prohibitively expensive. Yet the
      sensitivity of chemical shifts to structural details requires that the
      methodologies for performing MD and calculating NMR shifts be consistent. This
      work resolves these previously competing requirements by fitting classical force
      fields to reproduce ab initio forces. This methodology is first validated by
      reproducing the averaged chemical shifts found using ab initio molecular
      dynamics. Study of a supercell of L-alanine demonstrates that finite size effects
      can be significant when accounting for dynamics.

PMID- 20815563
TI  - Comparing modeling and measurements of the output power in chemical oxygen-iodine
      lasers: a stringent test of I2 dissociation mechanisms.
AB  - A parametric study of the output power of supersonic chemical oxygen-iodine
      lasers (COILs) is carried out, applying a kinetic-fluid dynamics model
      calculations as well as an analytical model and comparing the results to
      experimental studies. The I(2) dissociation mechanism recently suggested by
      Azyazov et al. [J. Chem. Phys. 130, 104306 (2009)], which was previously used for
      comparison of model calculations to measurements of the small signal gain [K.
      Waichman et al., J. Appl. Phys. 106, 063108 (2009)], is applied here for a
      similar, but more sensitive, comparison of the laser output power. The dependence
      of the power on iodine flow rate and on mirror transmission is studied for low
      and high pressure COILs, respectively. Good agreement between the calculated and
      measured power is obtained for both low and high pressure COILs only when the
      processes suggested by Azyazov et al. are included in the calculations. This is
      different from the situation for the gain where for high pressure COILs, the
      calculated values were insensitive to the assumed dissociation mechanism,
      although for low pressure the measurements were reproduced only by applying the
      Azyazov et al. mechanism. We believe that the results of the present work
      strongly support the application of this mechanism for modeling the COIL
      operation.

PMID- 20815564
TI  - Photoionization of iodine atoms: angular distributions and relative partial
      photoionization cross-sections in the energy region 11.0-23.0 eV.
AB  - Relative partial photoionization cross-sections and angular distribution
      parameters, beta, have been measured for the first, I(+)((3)P(2))<--I((2)P(3/2)),
      and fourth, I(+)((1)D(2))<--I((2)P(3/2)), (5p)(-1) photoelectron (PE) bands of
      atomic iodine, by performing angle-resolved constant-ionic-state (CIS)
      measurements on these PE bands in the photon energy range 11.0-23.0 eV. Three
      Rydberg series, two ns and one nd series, which converge to the I(+) (3)P(1)
      limit at 11.33 eV and four Rydberg series, two ns and two nd series, which
      converge to the I(+) (1)D(2) limit at 12.15 eV were observed in the first PE band
      CIS spectra. The fourth band CIS spectrum showed structure in the 12.9-14.1 eV
      photon energy range, which is also seen in the first band CIS spectra. This
      structure arises from excitation to ns and nd Rydberg states that are parts of
      series converging to the I(+) (1)S(0) limit we reported on earlier, as well as 5s
      ->5p excitations in the photon energy range 17.5-22.5 eV. These atomic iodine CIS
      spectra show reasonably good agreement with the equivalent spectra obtained for
      atomic bromine. The beta-plots for the first PE band recorded up to the I(+)
      (3)P(1) and I(+) (1)D(2) limits only show resonances corresponding to some of the
      5p-->nd excitations observed in the first band CIS spectra scanned to the I(+)
      (1)D(2) limit (12.15 eV). These plots are interpreted in terms of an angular
      momentum transfer model with the positive values of beta obtained on resonances
      corresponding to parity allowed j(t)=1 and 3 channels and the off-resonance
      negative beta values corresponding to parity unfavored channels, where j(t) is
      the quantum number for angular momentum transfer between the molecule, and the
      ion and photoelectron. The beta-plots recorded for iodine are significantly
      different from those obtained for atomic bromine. Comparison of the experimental
      CIS spectra and beta-plots with available theoretical results highlights the need
      for higher level calculations which include factors such as configuration
      interaction in the initial and final states, relativistic effects including spin
      orbit interaction, and autoionization via resonant Rydberg states.

PMID- 20815566
TI  - Photophysics of fluorinated benzene. I. Quantum chemistry.
AB  - The electronic structure of energetically low-lying excited singlet states of
      fluorobenzene molecules is investigated here. Increasing fluorine substitution
      alters the nature of the excited electronic states and the so-called perfluoro
      effect is observed for penta- and hexafluorobenzene. Detailed quantum chemistry
      calculations are carried out at the equation-of-motion coupled-cluster singles
      and doubles level of theory to establish the potential energy surfaces of the low
      lying electronic states of mono-, di- (ortho- and meta-), and pentafluorobenzene
      molecules. A sequence of low-energy conical intersections among the electronic
      potential energy surfaces is established. It is found that increasing fluorine
      substitution lowers the energy of the pisigma* electronic state and leads to
      conical intersections between the S(1) and S(2) electronic states of
      pentafluorobenzene. Existence of numerous conical intersections among the excited
      electronic states of these molecules forms the mechanistic details underlying
      their nonradiative internal conversion. In particular, the slow and biexponential
      fluorescence emission in pentafluorobenzene is attributed to the existence of low
      lying S(1)-S(2) conical intersections. The electronic structure data are analyzed
      in detail and the coupling mechanism among various electronic excited states of
      mono-, di-, and pentafluorobenzene molecules is established.

PMID- 20815565
TI  - Negative ion photoelectron spectroscopy of the copper-aspartic acid anion and its
      hydrated complexes.
AB  - Negative ions of copper-aspartic acid Cu(Asp)(-) and its hydrated complexes have
      been produced in the gas phase and studied by anion photoelectron spectroscopy.
      The vertical detachment energies (VDE) of Cu(Asp)(-) and Cu(Asp)(-)(H(2)O)(1,2)
      were determined to be 1.6, 1.95, and 2.20 eV, respectively. The spectral profiles
      of Cu(Asp)(-)(H(2)O)(1) and Cu(Asp)(-)(H(2)O)(2) closely resembled that of
      Cu(Asp)(-), indicating that hydration had not changed the structure of Cu(Asp)(-)
      significantly. The successive shifts to higher electron binding energies by the
      spectra of the hydrated species provided measures of their stepwise solvation
      energies. Density functional calculations were performed on anionic Cu(Asp)(-)
      and on its corresponding neutral. The agreement between the calculated and
      measured VDE values implied that the structure of the Cu(Asp)(-) complex
      originated with a zwitterionic form of aspartic acid in which a copper atom had
      inserted into the N-H bond.

PMID- 20815567
TI  - Photophysics of fluorinated benzene. II. Quantum dynamics.
AB  - Nuclear dynamics in the coupled electronic states of mono-, di-(ortho and meta),
      and pentafluorobenzene molecules is investigated here. Attempts are specifically
      made to understand the complexity and broadening of the recorded gas phase
      electronic absorption spectra of these molecules. Justification is also provided
      for the low quantum yield of fluorescence emission with increasing number of
      fluorine substitutions. The nuclear dynamics is simulated from first principles
      both by time-independent and time-dependent quantum mechanical methods. Potential
      energy surfaces of the low-lying excited electronic states of these molecules
      constructed in Paper I [Mondal and Mahapatra, J. Chem. Phys. 133, 084304 (2010)]
      are employed for the purpose. Theoretical results presented in this paper are
      compared with the available experimental data and the agreement between the two
      is found to be excellent. While structured electronic absorption bands are
      observed for the S(1) state of mono- and difluorobenzene molecules, the same for
      the pentafluorobenzene is broad and structureless. Occurrence of S(1)-S(2)
      conical intersections in pentafluorobenzene leads to a nonradiative internal
      conversion of the S(1) state in approximately 165 fs and contributes to the
      broadening of the S(1)<--S(0) absorption band and a biexponential decay of its
      fluorescence emission.

PMID- 20815568
TI  - Absorption in the Q-band region by isolated ferric heme+ and heme+(histidine) in
      vacuo.
AB  - Absorption by heme proteins is determined by the heme microenvironment that is
      often vacuumlike (hydrophobic pocket). Here we provide absorption spectra in the
      Q-band region of isolated ferric heme(+) and heme(+)(histidine) ions in vacuo to
      be used as references in protein biospectroscopy. Ions were photoexcited in an
      electrostatic storage ring and their decay monitored in time. Both ions display a
      triple band structure with maxima at 500, 518, and 530 nm. Previous attempts to
      study four-coordinate Fe(III)-heme(+) were hampered by the strong affinity of
      Fe(3+) for water and anions. Absorption at higher wavelengths is also measured,
      which is ascribed to charge-transfer transitions from the porphyrin to the iron.
      Finally, our data serve to benchmark theoretical calculations.

PMID- 20815569
TI  - Magnetostructural relations from a combined ab initio and ligand field analysis
      for the nonintuitive zero-field splitting in Mn(III) complexes.
AB  - The zero-field splitting (ZFS) of a model monometallic Mn(III) complex is
      theoretically studied as function of a systematic symmetry lowering. First, we
      treat the octahedral case for which the standard S.D.S model Hamiltonian cannot
      be applied due to a zero-field splitting in the absence of anisotropy induced by
      the spin-orbit coupling between the two spatial components of the (5)E(g) state
      at second-order of perturbation. Next, the symmetry is lowered to D(4h) and D(2h)
      and the anisotropic spin Hamiltonian is extracted using effective Hamiltonian
      theory. A simple relation is derived between the ratio E//D/ and the applied
      rhombic and axial distortions. Moreover, it is shown that close to O(h) symmetry,
      the orbital mixing due to spin-orbit coupling can be accurately described with
      Stevens fourth-order operators. The calculated tendencies are interpreted within
      a refined Racah plus ligand field model and it is shown that the ZFS parameters
      in Mn(III) complexes follow special rules that are nonintuitive compared to other
      d(n) configurations. Finally, some angular distortions are applied to study their
      effect on the anisotropy.

PMID- 20815570
TI  - The van der Waals potential of the magnesium dimer.
AB  - The ground state van der Waals potential of the magnesium dimer is described by
      the Tang-Toennies potential model, which requires five essential parameters.
      Among them, the three dispersion coefficients C(6), C(8), and C(10) are available
      from accurate ab initio calculations. The other two are the Born-Mayer parameters
      in A exp(-bR). In this paper, we show that A and b can be determined from the
      self-consistent Hartree-Fock calculations and the experimental dissociation
      energy D(0). The predicted well depth D(e) and equilibrium distance R(e) are in
      nearly perfect agreement with the experiment. In fact, the entire potential
      energy curve, which is given by a single analytic function, is in excellent
      agreement with the pointwise potential energies constructed from the
      spectroscopic measurements in the interval of 6a(0)-14a(0) and in good agreement
      with the experimental repulsive potential determined from Franck-Condon factors
      of the bound-free transitions for R less than 6a(0). The reduced potential of
      Mg(2) is analyzed in terms of its components, and the number of terms in the
      dispersion series necessary for convergence is investigated.

PMID- 20815571
TI  - HY...N2 and HXeY...N2 complexes in solid xenon (Y=Cl and Br): unexpected
      suppression of the complex formation for deposition at higher temperature.
AB  - The 1:1 complexes of HY and HXeY (Y=Cl and Br) with nitrogen are characterized by
      FTIR spectroscopy in a Xe matrix. These complexes show small blue shifts of the
      HY and H-Xe stretching frequencies with respect to the monomers (ca. +10 cm(-1)).
      In the HXeY...N(2) synthesis procedure, a HY/N(2)/Xe matrix with HY...N(2)
      complexes is first photolyzed at 193 nm to yield isolated H and Y...N(2)
      fragments. At the second step, annealing at ca. 40 K activates mobility of H
      atoms and promotes the H+Xe+Y...N(2) reaction. It is quite remarkable that the
      HY...N(2) and consequently HXeY...N(2) complexes are observed in Xe matrices
      deposited at relatively low temperature (below ca. 35 K). For Xe matrices
      deposited above ca. 40 K, HY molecules do not form a complex with nitrogen and
      the HXeY...N(2) complex does not appear after photolysis and annealing; however,
      this observation is not explained in this article.

PMID- 20815572
TI  - Electronic-resonance-enhanced coherent anti-Stokes Raman scattering of nitric
      oxide: saturation and Stark effects.
AB  - A theoretical analysis of electronic-resonance-enhanced (ERE) coherent anti
      Stokes Raman scattering (CARS) of NO is described. The time-dependent density
      matrix equations for the nonlinear ERE-CARS process are derived and manipulated
      into a form suitable for direct numerical integration. In the ERE-CARS
      configuration considered in this paper, the pump and Stokes beams are far from
      electronic-resonance. The visible 532 and 591 nm laser beams are used to excite Q
      branch Raman resonances in the vibrational bands of the X (2)Pi electronic state
      of NO. An ultraviolet probe beam at 236 nm is used to excite P-, Q-, or R-branch
      transitions in the (v'=0, v"=1) band of the A (2)Sigma(+)-X (2)Pi electronic
      system of NO molecule. Experimental spectra are obtained either by scanning the
      ultraviolet probe beam while keeping the Stokes frequency fixed (probe scans) or
      by scanning the Stokes frequency while keeping the probe frequency fixed (Stokes
      scans). The calculated NO ERE-CARS spectra are compared with experimental
      spectra, and good agreement is observed between theory and experiment in terms of
      spectral peak locations and relative intensities. The effects of saturation of
      the two-photon Raman-resonant Q-branch transitions, the saturation of a one
      photon electronic-resonant P-, Q-, or R-branch transitions in the A (2)Sigma(+)-X
      (2)Pi electronic system, and the coupling of these saturation processes are
      investigated. The coupling of the saturation processes for the probe and Raman
      transitions is complex and exhibits behavior similar to that observed in the
      electromagnetic induced transparency process. The probe scan spectra are
      significantly affected by Stark broadening due to the interaction of the pump and
      Stokes radiation with single-photon resonances between the upper vibration
      rotation probe level in the A (2)Sigma(+) electronic levels and vibration
      rotation levels in higher lying electronic levels. The ERE-CARS signal intensity
      is found to be much less sensitive to variations in the collisional dephasing
      rates under saturation conditions.

PMID- 20815573
TI  - Photodissociation of nitromethane cluster anions.
AB  - Three types of anionic fragments are observed in the photodissociation of
      nitromethane cluster anions, (CH(3)NO(2))(n)(-), n=1-6, at 355 nm: NO(2)(
      )(CH(3)NO(2))(k), (CH(3)NO(2))(k)(-), and OH(-) (k<n). The fragmentation trends
      are consistent with the parent clusters containing a monomer-anion core,
      CH(3)NO(2)(-), solvated by n-1 neutral nitromethane molecules. The NO(2)(
      )(CH(3)NO(2))(k) and OH(-) fragments formed from these clusters are described as
      core-dissociation products, while the (CH(3)NO(2))(k)(-) fragments are attributed
      to energy transfer from excited CH(3)NO(2)(-) into the solvent network or a core
      dissociation-recombination (caging) mechanism. As with other cluster families,
      the fraction of caged photofragments shows an overall increase with increasing
      cluster size. The low-lying A(2)A' and/or B(2)A' electronic states of CH(3)NO(2)(
      ) are believed responsible for photoabsorption leading to dissociation to NO(2)(
      ) based fragments, while the C(2)A" state is a candidate for the OH(-) pathway.
      Compared to neutral nitromethane, the photodissociation of CH(3)NO(2)(-) requires
      lower energy photons because the photochemically active electron occupies a high
      energy pi* orbital (which is vacant in the neutral). Although the electronic
      states in the photodissociation of CH(3)NO(2) and CH(3)NO(2)(-) are different,
      the major fragments, CH(3)+NO(2) and CH(3)+NO(2)(-), respectively, both form via
      C-N bond cleavage.

PMID- 20815574
TI  - Melting of Sn at high pressure: comparisons with Pb.
AB  - Measurements for Sn, made using the laser-heated diamond cell, are reported that
      extend the melting curve to 68 GPa and 2300 K. Initially the melting temperature
      of Sn increases linearly with increasing pressure (dT/dP approximately 40 K/GPa)
      and near 38 GPa (2200 K) the melting curve flattens (dT/dP approximately 0),
      indicating a zero volume phase change at melting. The results are in good
      agreement with previously reported shock melting studies. In comparison to Sn the
      melting curve of Pb is relatively linear to 100 GPa, the highest pressure at
      which measurements have been made.

PMID- 20815575
TI  - Quantum-classical description of environmental effects on electronic dynamics at
      conical intersections.
AB  - Quantum-classical Liouville theory is used to simulate the dynamics of systems
      containing conical intersections. In particular quantum dynamical effects on the
      electronic population transfer and coherence in a quantum subsystem that arise
      from the presence of an environment are studied. The environment, in turn, is
      partitioned into an immediate environment representing, say, local molecular
      vibrations, and a bath representing other degrees of freedom. Population transfer
      may be enhanced or suppressed, depending on the relative values of the
      characteristic frequencies of the immediate environment and bath. Electronic
      decoherence and the destruction of geometric phase effects were observed for bath
      frequencies that are large relative to the molecular vibrations. The dynamics at
      higher dimensional conical intersections was found to be very sensitive to the
      environmental coupling. When a single collective solvent coordinate couples
      directly to the electronic subsystem, the characteristic frequency of the new
      coordinate, relative to that of the nuclear vibrational modes, has a strong
      effect on the population dynamics. The results also serve as a test of the QCL
      dynamical scheme for future applications to more detailed molecular descriptions
      of condensed phase environments for conical intersection dynamics.

PMID- 20815576
TI  - Meir-Wingreen formula for heat transport in a spin-boson nanojunction model.
AB  - An analog of the Meir-Wingreen formula for the steady-state heat current through
      a model molecular junction is derived. The expression relates the heat current to
      correlation functions of operators acting only on the degrees of freedom of the
      molecular junction. As a result, the macroscopic heat reservoirs are not treated
      explicitly. This allows one to exploit methods based on a reduced description of
      the dynamics of a relatively small part of the overall system to evaluate the
      heat current through a molecular junction. The derived expression is applied to
      calculate the steady-state heat current in the weak coupling limit, where the
      Redfield theory is used to describe the reduced dynamics of the molecular
      junction. The results are compared with those of previously developed approximate
      and numerically exact methods.

PMID- 20815577
TI  - Studies on electrostatic interactions of colloidal particles in two dimensions: a
      modeling approach.
AB  - We study the effective electrostatic interactions between a pair of charged
      colloidal particles without salt ions while the system is confined in two
      dimensions. In particular, we use a simplified model to elucidate the effects of
      rotational fluctuations in counterion distribution. The results exhibit effective
      colloidal attractions under appropriate conditions. Meanwhile, long-range
      repulsions persist over most of our studied cases. The repulsive forces arise
      from the fact that in two dimensions, the charged colloids cannot be perfectly
      screened by counterions, as the residual quadrupole moments contribute to the
      repulsions at longer range. By applying multiple expansions, we find that the
      attractive forces observed at short range are mainly contributed by electrostatic
      interactions among higher-order electric moments. We argue that the scenario for
      attractive interactions discussed in this work is applicable to systems of
      charged nanoparticles or colloidal solutions with macroions.

PMID- 20815578
TI  - A parameter-free prediction of simulated crystal nucleation times in the Lennard
      Jones system: from the steady-state nucleation to the transient time regime.
AB  - Large scale simulations of crystal nucleation from the liquid are performed using
      the Lennard-Jones potential to determine the time required for nucleation. By
      considering both transient and finite-size effects, we for the first time
      successfully predict the nucleation time without any parameter fitting in the
      Lennard-Jones system. All necessary parameters are derived from separate,
      equilibrium simulations. At small undercoolings, large system size effects are
      observed. The required system size is not only determined by the size of the
      critical nuclei, but also the characteristic spacing between them. Two distinct
      nucleation regions are predicted by theory and observed by the simulations, which
      are dominated by the transient time and the steady-state nucleation time,
      respectively.

PMID- 20815579
TI  - On the proton kinetic energy in H2O and in nanotube water.
AB  - We calculated the kinetic energies of the H-atom in ice Ih between 5 and 269 K
      and in water in the range 293-673 K. To do so we used the literature optical
      vibration frequencies of ice and water of the different phases assuming the
      harmonic approximation and decoupling between the degrees of freedom of
      translation, rotation (libration), and internal vibrations. Apart for ice at 269
      K, good agreement was obtained with published experimental values for both cases.
      Similar agreement with experiment was found for the case of water confined in 14
      A diameter carbon nanotubes at 268 K. However, serious deviations from measured
      values were found in nanotube water in the range 5-230 K. Possible reasons for
      those deviations are discussed.

PMID- 20815580
TI  - Softness dependence of the anomalies for the continuous shouldered well
      potential.
AB  - By molecular dynamic simulations we study a system of particles interacting
      through a continuous isotropic pairwise core-softened potential consisting of a
      repulsive shoulder and an attractive well. The model displays a phase diagram
      with three fluid phases: a gas-liquid critical point, a liquid-liquid critical
      point, and anomalies in density, diffusion, and structure. The hierarchy of the
      anomalies is the same as for water. Here we study in a systematic way the effect
      on the anomalies of varying the softness of the potential. We find that, making
      the soft-core steeper and more penetrable, the regions of density and diffusion
      anomalies contract in the T-rho plane, while the region of structural anomaly is
      weakly affected. Therefore, a liquid can have anomalous structural behavior
      without having density or diffusion anomalies. We show that, by considering as
      effective distances those corresponding to the maxima of the first two peaks of
      the radial distribution function g(r) in the high-density liquid, we can
      generalize to continuous two-scale potentials a criterion for the occurrence of
      the anomalies of density and diffusion, originally proposed for discontinuous
      potentials. However, we observe that the knowledge of the structural behavior
      within the first two coordination shells of the liquid is not enough to
      establish, in general, the occurrence of the anomalies. By introducing the
      density derivative of the cumulative order integral of the excess entropy,
      measuring shell by shell the amount of order in the liquid, we show that the
      anomalous behavior is regulated by the structural order at distances as large as
      the fourth coordination shell. By comparing the results for different softness of
      the potential, we conclude that the disappearance of the density and diffusion
      anomalies for the steeper potentials is due to a more structured short-range
      order. All these results increase our understanding on how, knowing the
      interaction potential, we can evaluate the possible presence of anomalies for a
      liquid.

PMID- 20815581
TI  - An exciton scattering model for carrier multiplication in semiconductor
      nanocrystals: theory.
AB  - The effect of carrier multiplication (CM) in semiconductor nanocrystals is
      systematically treated by employing an exciton scattering approach. Using
      projection operators, we reduce the Coulomb coupled multiexciton dynamics to
      scattering dynamics in the space spanning both single- and biexciton states. We
      derive a closed set of equations determining the scattering matrix elements. This
      allows us to interpret CM dynamics as a series of odd-order interband scattering
      events. Using the time-dependent density matrix formalism, we provide a rigorous
      description of the CM dynamics induced by a finite-time pump pulse. Within this
      approach, both processes of single- and biexciton photogeneration and the
      consequent population relaxation are treated on the same footing. This approach
      provides a framework for numerical calculations and for comparisons of the
      quantum efficiencies associated with each process. For applications, the limit of
      weak interband Coulomb coupling is considered. Finally, we demonstrate that three
      previously used theoretical models can be recovered as limiting cases of our
      exciton scattering model.

PMID- 20815582
TI  - A kinetic Ising model study of dynamical correlations in confined fluids:
      emergence of both fast and slow time scales.
AB  - Experiments and computer simulation studies have revealed existence of rich
      dynamics in the orientational relaxation of molecules in confined systems such as
      water in reverse micelles, cyclodextrin cavities, and nanotubes. Here we
      introduce a novel finite length one dimensional Ising model to investigate the
      propagation and the annihilation of dynamical correlations in finite systems and
      to understand the intriguing shortening of the orientational relaxation time that
      has been reported for small sized reverse micelles. In our finite sized model,
      the two spins at the two end cells are oriented in the opposite directions to
      mimic the effects of surface that in real system fixes water orientation in the
      opposite directions. This produces opposite polarizations to propagate inside
      from the surface and to produce bulklike condition at the center. This model can
      be solved analytically for short chains. For long chains, we solve the model
      numerically with Glauber spin flip dynamics (and also with Metropolis single-spin
      flip Monte Carlo algorithm). We show that model nicely reproduces many of the
      features observed in experiments. Due to the destructive interference among
      correlations that propagate from the surface to the core, one of the rotational
      relaxation time components decays faster than the bulk. In general, the
      relaxation of spins is nonexponential due to the interplay between various
      interactions. In the limit of strong coupling between the spins or in the limit
      of low temperature, the nature of relaxation of the spins undergoes a qualitative
      change with the emergence of a homogeneous dynamics where decay is predominantly
      exponential, again in agreement with experiments.

PMID- 20815583
TI  - Dissociation of water over Ti-decorated C60.
AB  - Using first-principles calculations we have studied the reactions of water over
      Ti-decorated C(60) in order to assess the possibility of using this system as a
      catalyst for water dissociation. Our results show that a single water molecule
      dissociates exothermically with a small energy barrier on a single Ti atom
      adsorbed on C(60). After dissociation, both H(+) and OH(-) ions bind strongly to
      the Ti atom, which serves as an effective reactive center that facilitates
      further water splitting. When a second water molecule is introduced, we observe
      the formation of a hydrogen molecule with a comparably small activation barrier.
      When the coverage of Ti on C(60) is increased, the formation of Ti dimer does not
      change the catalytic effect of TiC(60) complex very much. Our results provide
      fundamental insights into the mechanisms of water dissociation on such a
      prototypical nanostructure and suggest that Ti-decorated C(60) could be exploited
      as a catalyst for water splitting to generate hydrogen.

PMID- 20815584
TI  - Freezing of mixtures confined in silica nanopores: experiment and molecular
      simulation.
AB  - Freezing of mixtures confined in silica nanopores is investigated by means of
      experiment and molecular simulation. The experiments consist of differential
      scanning calorimetry and dielectric relaxation spectroscopy measurements for
      CCl(4)/C(6)H(5)Br mixtures confined in Vycor having pores with a mean diameter of
      about D=4.2 nm. Molecular simulations consist of grand canonical Monte Carlo
      simulations combined with the parallel tempering technique for Lennard-Jones
      Ar/Kr mixtures confined in a silica cylindrical nanopore with a diameter of D=3.2
      nm. The experimental and molecular simulation data provide a consistent picture
      of freezing of mixtures in cylindrical silica nanopores having a size smaller
      than ten times the size of the confined molecules. No sharp change in the
      properties of the confined mixture occurs upon melting, which suggests that the
      confined system does not crystallize. In the case of the molecular simulations,
      this result is confirmed by the fact that except for the contact layer, the
      percentage of crystal-like atoms is less than 6% (whatever the temperature). The
      molecular simulations also show that the composition of the mixture is shifted,
      upon confinement, toward the component having the strongest wall/fluid
      attraction.

PMID- 20815585
TI  - Multiple localized states and magnetic orderings in partially open zigzag carbon
      nanotube superlattices: an ab initio study.
AB  - Using ab initio calculations, we examine the electronic and magnetic properties
      of partially open (unzipped) zigzag carbon nanotube (CNT) superlattices. It is
      found that depending on their opening degree, these superlattices can exhibit
      multiple localized states around the Fermi energy. More importantly, some
      electronic states confined in some parts of the structure even have special
      magnetic orderings. We demonstrate that, as a proof of principle, some partially
      open zigzag CNT superlattices are by themselves giant (100%) magnetoresistive
      devices. Furthermore, the localized (and spin-polarized) states as well as the
      band gaps of the superlattices could be further modulated by external electric
      fields perpendicular to the tube axis. We believe that these results will open
      the way to the production of novel nanoscale electronic and spintronic devices.

PMID- 20815586
TI  - Molecular dynamics simulation of O2 sticking on Pt(111) using the ab initio based
      ReaxFF reactive force field.
AB  - The molecular dynamics technique with the ab initio based classical reactive
      force field ReaxFF is used to study the adsorption dynamics of O(2) on Pt(111)
      for both normal and oblique impacts. Overall, good quantitative agreement with
      the experimental data is found at low incident energies. Specifically, our
      simulations reproduce the characteristic minimum of the trapping probability at
      kinetic incident energies around 0.1 eV. This feature is determined by the
      presence of a physisorption well in the ReaxFF potential energy surface (PES) and
      the progressive suppression of a steering mechanism when increasing the
      translational kinetic energy (or the molecule's rotational energy) because of
      steric hindrance. In the energy range between 0.1 and 0.4 eV, the sticking
      probability increases, similar to molecular beam sticking data. For very
      energetic impacts (above 0.4 eV), ReaxFF predicts sticking probabilities lower
      than experimental sticking data by almost a factor of 3 due to an overall less
      attractive ReaxFF PES compared to experiments and density functional theory. For
      oblique impacts, the trapping probability is reduced by the nonzero parallel
      momentum because of the PES corrugation and does not scale with the total
      incident kinetic energy. Furthermore, our simulations predict quasispecular
      (slightly supraspecular) distributions of angles of reflection, in accordance
      with molecular beam experiments. Increasing the beam energy (between 1.2 and 1.7
      eV) causes the angular distributions to broaden and to exhibit a tail toward the
      surface normal because molecules have enough momentum to get very near the
      surface and thus probe more corrugated repulsive regions of the PES.

PMID- 20815587
TI  - CO oxidation on PdO surfaces.
AB  - Density functional calculations were performed in order to investigate CO
      oxidation on two of the most stable bulk PdO surfaces. The most stable PdO(100)
      surface, with oxygen excess, is inert against CO adsorption, whereas strong
      adsorption on the stoichiometric PdO(101) surface leads to favorable oxidation
      via the Langmuir-Hinshelwood mechanism. The reaction with a surface oxygen atom
      has an activation energy of 0.66 eV, which is comparable to the lowest activation
      energies observed on metallic surfaces. However, the reaction rate may be limited
      by the coverage of molecular oxygen. Actually, the reaction with the site
      blocking molecular oxygen is slightly more favorable, enabling also possible
      formation of carbonate surface species at low temperatures. The extreme activity
      of strongly bonded surface oxygen atoms is more greatly emphasized on the
      PdO(100)-O surface. The direct reaction without adsorption, following the Eley
      Rideal mechanism and taking advantage of the reaction tunnel provided by the
      adjacent palladium atom, has an activation energy of only 0.24 eV. The reaction
      mechanism and activation energy for the palladium activated CO oxidation on the
      most stable PdO(100)-O surface are in good agreement with experimental
      observations.

PMID- 20815588
TI  - Clustering in polar media.
AB  - Clustering prevails in water-soluble polymers and biological macromolecules. It
      has also been observed in polar solvent mixtures. The possible causes of
      clustering are discussed. A systematic investigation of clustering in
      poly(ethylene oxide)/d-water solutions has been undertaken using the small-angle
      neutron scattering method. The poly(ethylene oxide) monomer is formed of an
      oxygen atom and an ethylene group. Using the random phase approximation, partial
      Flory-Huggins interaction parameters for the three pairs (oxygen/d-water,
      ethylene/d-water, and oxygen/ethylene) are derived. Results show that the first
      two (oxygen/d-water and ethylene/d-water) are characterized by a lower critical
      solution temperature phase behavior (whereby phase separation occurs upon
      heating), while the third one (oxygen/ethylene) is characterized by an upper
      critical solution temperature phase diagram (whereby phase separation occurs upon
      cooling). It is argued that clustering is caused by the increasing repulsive
      interaction between oxygen and ethylene for decreasing temperature and increasing
      polymer volume fraction. This leads to increasing attractive interactions between
      ethylene groups that stick together.

PMID- 20815589
TI  - Fluids density functional theory studies of supramolecular polymers at a hard
      surface.
AB  - We have applied a fluids density functional theory based on that of Yu and Wu [J.
      Chem. Phys. 116, 7094 (2002)] to treat reversible supramolecular polymers near a
      hard surface. This approach combines a hard-sphere fluids density functional
      theory with the first-order thermodynamic perturbation theory of Wertheim. The
      supramolecular polymers are represented in the theory by hard-spheres with two
      associating sites. We explore the effects of the bonding scheme, monomer
      concentration, and association energy upon the equilibrium chain sizes and the
      depletion lengths. This study is performed on simple systems containing two-site
      monomers and binary mixtures of two-site monomers combined with end stopper
      monomers which have only a single association site. Our model has correct
      behavior in the dilute and overlap regimes and the bulk results can be easily
      connected to simpler random-flight models. We find that there is a nonmonotonic
      behavior of the depletion length of the polymers as a function of concentration
      and that this depletion length can be controlled through the concentration of end
      stoppers. These results are applicable to the study of colloidal dispersions in
      supramolecular polymer solutions.

PMID- 20815590
TI  - Quantum chemistry and molecular dynamics studies of the entropic elasticity of
      localized molecular kinks in polyisoprene chains.
AB  - We investigate the thermodynamic consequences of the distribution of rotational
      conformations of polyisoprene on the elastic response of a network chain. In
      contrast to the classical theory of rubber elasticity, which associates the
      elastic force with the distribution of end-to-end distances, we find that the
      distribution of chain contour lengths provides a simple mechanism for an elastic
      force. Entropic force constants were determined for small contour length
      extensions of chains constructed as a series of localized kinks, with each kink
      containing between one and five cis-1,4-isoprene units. The probability
      distributions for the kink end-to-end distances were computed by two methods: (1)
      by constructing a Boltzmann distribution from the lengths corresponding to the
      minimum energy dihedral rotational conformations, obtained by optimizing isoprene
      using first principles density functional theory, and (2) by sampling the
      trajectories of molecular dynamics simulations of an isolated molecule composed
      of five isoprene units. Analogous to the well-known tube model of elasticity, we
      make the assumption that, for small strains, the chain is constrained by its
      surrounding tube, and can only move, by a process of reptation, along the
      primitive path of the contour. Assuming that the chain entropy is Boltzmann's
      constant times the logarithm of the contour length distribution, we compute the
      tensile force constants for chain contour length extension as the change in
      entropy times the temperature. For a chain length typical of moderately
      crosslinked rubber networks (78 isoprene units), the force constants range
      between 0.004 and 0.033 N/m, depending on the kink size. For a cross-linked
      network, these force constants predict an initial tensile modulus of between 3
      and 8 MPa, which is comparable to the experimental value of 1 MPa. This mechanism
      is also consistent with other thermodynamic phenomenology.

PMID- 20815591
TI  - A molecular dynamics study on the transport of a charged biomolecule in a
      polymeric adsorbent medium and its adsorption onto a charged ligand.
AB  - The transport of a charged adsorbate biomolecule in a porous polymeric adsorbent
      medium and its adsorption onto the covalently immobilized ligands have been
      modeled and investigated using molecular dynamics modeling and simulations as the
      third part of a novel fundamental methodology developed for studying ion-exchange
      chromatography based bioseparations. To overcome computational challenges, a
      novel simulation approach is devised where appropriate atomistic and coarse grain
      models are employed simultaneously and the transport of the adsorbate is
      characterized through a number of locations representative of the progress of the
      transport process. The adsorbate biomolecule for the system studied in this work
      changes shape, orientation, and lateral position in order to proceed toward the
      site where adsorption occurs and exhibits decreased mass transport coefficients
      as it approaches closer to the immobilized ligand. Furthermore, because the
      ligands are surrounded by counterions carrying the same type of charge as the
      adsorbate biomolecule, it takes the biomolecule repeated attempts to approach
      toward a ligand in order to displace the counterions in the proximity of the
      ligand and to finally become adsorbed. The formed adsorbate-ligand complex
      interacts with the counterions and polymeric molecules and is found to evolve
      slowly and continuously from one-site (monovalent) interaction to multisite
      (multivalent) interactions. Such a transition of the nature of adsorption reduces
      the overall adsorption capacity of the ligands in the adsorbent medium and
      results in a type of surface exclusion effect. Also, the adsorption of the
      biomolecule also presents certain volume exclusion effects by not only directly
      reducing the pore volume and the availability of the ligands in the adjacent
      regions, but also causing the polymeric molecules to change to more compact
      structures that could further shield certain ligands from being accessible to
      subsequent adsorbate molecules. These findings have significant practical
      implications to the design and construction of polymeric porous adsorbent media
      for effective bioseparations and to the synthesis and operation of processes
      employed in the separation of biomolecules. The modeling and analysis methods
      presented in this work could also be suitable for the study of biocatalysis where
      an enzyme is immobilized on the surface of the pores of a porous medium.

PMID- 20815592
TI  - Kinetics of hexagonal cylinders to face-centered cubic spheres transition of
      triblock copolymer in selective solvent: Brownian dynamics simulation.
AB  - The kinetics of the transformation from the hexagonal packed cylinder (hex) phase
      to the face-centered-cubic (fcc) phase was simulated using Brownian dynamics for
      an ABA triblock copolymer in a selective solvent for the A block. The kinetics
      was obtained by instantaneously changing either the temperature of the system or
      the well-depth of the Lennard-Jones potential. Detailed analysis showed that the
      transformation occurred via a rippling mechanism. The simulation results
      indicated that the order-order transformation was a nucleation and growth process
      when the temperature of the system instantly jumped from 0.8 to 0.5. The time
      evolution of the structure factor obtained by Fourier transformation showed that
      the peak intensities of the hex and fcc phases could be fit well by an Avrami
      equation.

PMID- 20815593
TI  - High-frequency viscosity of concentrated porous particles suspensions.
AB  - We determine the high-frequency limiting shear viscosity, eta(infinity), in
      colloidal suspensions of rigid, uniformly porous spheres of radius a as a
      function of volume fraction phi and (inverse) porosity parameter x. Our study
      covers the complete fluid-state regime. The flow inside the spheres is modeled by
      the Debye-Bueche-Brinkman equation using the boundary condition that fluid
      velocity and stress change continuously across the sphere surfaces. The many
      sphere hydrodynamic interactions in concentrated systems are fully accounted for
      by a precise hydrodynamic multipole method encoded in our HYDROMULTIPOLE program
      extended to porous particles. A truncated virial expansion is used to derive an
      accurate and easy-to-use generalized Saito; formula for eta(infinity). The
      simulation data are used to test the performance of two simplifying effective
      particle models. The first model describes the effective particle as a nonporous
      sphere characterized by a single effective radius a(eff)(x)<a. In the more
      refined second model, the porous spheres are modeled as spherical annulus
      particles with an inner hydrodynamic radius a(eff)(x) defining the nonporous dry
      core and characterizing hydrodynamic interactions, and an outer excluded volume
      radius a characterizing the unchanged direct interactions. Only the second model
      is in a satisfactory agreement with the simulation data.

PMID- 20815594
TI  - Depth dependent dynamics in the hydration shell of a protein.
AB  - We study the dynamics of hydration water/protein association in folded proteins
      using lysozyme and myoglobin as examples. Extensive molecular dynamics
      simulations are performed to identify underlying mechanisms of the dynamical
      transition that corresponds to the onset of amplified atomic fluctuations in
      proteins. The results indicate that the number of water molecules within a cutoff
      distance of each residue scales linearly with protein depth index and is not
      affected by the local dynamics of the backbone. Keeping track of the water
      molecules within the cutoff sphere, we observe an effective residence time,
      scaling inversely with depth index at physiological temperatures while the
      diffusive escape is highly reduced below the transition. A depth independent
      orientational memory loss is obtained for the average dipole vector of the water
      molecules within the sphere when the protein is functional. While below the
      transition temperature, the solvent is in a glassy state, acting as a solid crust
      around the protein, inhibiting any large scale conformational fluctuations. At
      the transition, most of the hydration shell unfreezes and water molecules
      collectively make the protein more flexible.

PMID- 20815595
TI  - The role of stochasticity on compactness of the native state of protein peptide
      backbone.
AB  - A restricted angular random-walk model to build up polypeptide structures, which
      encompasses properties of the dihedral-angle Ramachandran map of folded proteins,
      is proposed to study the role of stochasticity on the compactness of the native
      state of proteins. Sample structures will be built with lengths ranging from 125
      up to 400 amino acids for the different fractions of secondary structure motifs,
      from which dihedral angles were randomly chosen according to narrow Gaussian
      probability distributions. Physical properties of these polypeptide protein
      backbones such as the radius of gyration, the compactness parameter, the number
      of contacts, and the associated energy were computed and analyzed from an
      ensemble of thousands of realizations of protein peptide chains built with
      different rates of alpha-helix or beta-strand motifs. Such geometric and physical
      parameters are compared to data from several globular proteins extracted from the
      Protein Data Bank indicating that a certain (small fraction) randomness is an
      essential ingredient for achieving the folded state of proteins, suggesting that
      they are neither driven by deterministic nor random-walk processes.

PMID- 20815596
TI  - Invited review article: IceCube: an instrument for neutrino astronomy.
AB  - Neutrino astronomy beyond the Sun was first imagined in the late 1950s; by the
      1970s, it was realized that kilometer-scale neutrino detectors were required. The
      first such instrument, IceCube, is near completion and taking data. The IceCube
      project transforms 1 km(3) of deep and ultratransparent Antarctic ice into a
      particle detector. A total of 5160 optical sensors is embedded into a gigaton of
      Antarctic ice to detect the Cherenkov light emitted by secondary particles
      produced when neutrinos interact with nuclei in the ice. Each optical sensor is a
      complete data acquisition system including a phototube, digitization electronics,
      control and trigger systems, and light-emitting diodes for calibration. The light
      patterns reveal the type (flavor) of neutrino interaction and the energy and
      direction of the neutrino, making neutrino astronomy possible. The scientific
      missions of IceCube include such varied tasks as the search for sources of cosmic
      rays, the observation of galactic supernova explosions, the search for dark
      matter, and the study of the neutrinos themselves. These reach energies well
      beyond those produced with accelerator beams. The outline of this review is as
      follows: neutrino astronomy and kilometer-scale detectors, high-energy neutrino
      telescopes: methodologies of neutrino detection, IceCube hardware, high-energy
      neutrino telescopes: beyond astronomy, and future projects.

PMID- 20815597
TI  - Optical coherence tomography monitoring of angioplasty balloon inflation in a
      deployment tester.
AB  - We present an innovative integration of an intravascular optical coherence
      tomography probe into a computerized balloon deployment system to monitor the
      balloon inflation process. The high-resolution intraluminal imaging of the
      balloon provides a detailed assessment of the balloon quality and, consequently,
      a technique to improve the balloon manufacturing process. A custom-built swept
      source optical coherence tomography system is used for real-time imaging. A
      semicompliant balloon with a nominal diameter of 4 mm is fabricated for the
      experiments. Imaging results correspond to balloon deployment in air and inside
      an artery phantom. A characterization of the balloon diameter, wall thickness,
      compliance, and elastic modulus is provided, based on image segmentation. Using
      the images obtained from the probe pullback, a three-dimensional visualization of
      the inflated balloon is presented.

PMID- 20815598
TI  - A lightweight near-infrared spectrometer for the detection of trace atmospheric
      species.
AB  - This paper describes the development and deployment of a lightweight in situ near
      infrared tunable diode laser absorption spectrometer (TDLAS) for balloon-borne
      measurements of trace species such as methane in the upper troposphere and
      stratosphere. The key feature of the instrument design is its ability to provide
      high sensitivity measurements with better than 1 part in 10(6) Hz(-1/2) optical
      sensitivity in a lightweight package weighing as little as 6 kg, and maintaining
      this level of performance over the wide range of conditions experienced during
      field measurements. The absolute accuracy for methane measurements is
      approximately 10% limited by uncertainties in determining the gas temperature in
      the measurement volume. The high sensitivity and high temporal resolution (2.3 s
      measurement period) enables details of the fine-scale structure in the atmosphere
      to be measured. The TDLAS instrument has been used on a number of major
      international measurement campaigns. Intercomparison with other instruments
      during these campaigns have confirmed the comparability of the results from this
      instrument with measurements made by a range of other techniques, and
      demonstrated the instruments suitability for studies of atmospheric dynamics,
      transport, and mixing processes.

PMID- 20815599
TI  - System for time resolved spectral studies of pulsed atmospheric discharges in the
      visible to vacuum ultraviolet range.
AB  - Vacuum ultraviolet (VUV) emission is believed to play a major role in the
      development of plasma streamers in pulsed atmospheric discharges, but detection
      of VUV light is difficult in pulsed experiments at atmospheric pressures. Since
      VUV light is absorbed in most standard optical materials as well, careful
      attention must be given to the selection of the lens and mirror optics used in
      these studies. Of highest interest is the VUV emission during the initial stage
      of pulsed atmospheric discharges, which has a typical duration in the nanosecond
      regime. An experiment was designed to study this fast initial stage of VUV
      emission coupled with fast optical imaging of streamer propagation, both with
      temporal resolution on the order of nanoseconds. A repetitive solid-state high
      voltage pulser was constructed which produces triggered flashover discharges with
      low jitter and consistent pulse amplitude. VUV emission is captured utilizing
      both photomultiplier and intensified charge-coupled device detectors during the
      fast stage of streamer propagation. These results are discussed in context with
      the streamer formation photographed in the visible wavelength regime with 3 ns
      exposure time.

PMID- 20815600
TI  - Design and characterization of 2.45 GHz electron cyclotron resonance plasma
      source with magnetron magnetic field configuration for high flux of hyperthermal
      neutral beam.
AB  - A 2.45 GHz electron cyclotron resonance (ECR) source with a magnetron magnetic
      field configuration was developed to meet the demand of a hyperthermal neutral
      beam (HNB) flux on a substrate of more than 1x10(15) cm(-2) s(-1) for industrial
      applications. The parameters of the operating pressure, ion density, electron
      temperature, and distance between the neutralization plate and the substrate for
      the HNB source are specified in a theoretical analysis. The electron temperature
      and the ion density are measured to characterize the ECR HNB source using a
      Langmuir probe and optical emission spectroscopy. The parameters of the ECR HNB
      source are in good agreement with the theoretically specified parameters.

PMID- 20815601
TI  - High homogeneity 25 cm low-energy rf ion source with inherent electron
      compensation.
AB  - A 25 cm single-grid low-energy rf ion source with inherent electron compensation
      is described and characterized. Measurements were carried out using Ar and CF(4)
      filling gas. The dependence of the ion beam current to the target as well as the
      current partition between the beam fast and slow ions on the rf discharge
      pressure for both filling gases is discussed. The unique ability of generation of
      coinciding ion and electron flows is demonstrated and the measured ion and
      electron energy distribution functions are presented as well. The developed broad
      ion beam source is able of providing 0.5-5 mA/cm(2) current density in the low
      ion energy range of 50-250 eV, with possibility of independent current density
      and energy control. It is shown that complementing the rf plasma source with a
      profiling electrode allows for CF(4) ion source operation attaining +/-5% ion
      beam uniformity over 250 mm in diameter. The presented CF(4) etching test results
      exhibit the possibility of highly directional anisotropic Si and SiO(2) etching
      utilizing the developed single grid rf ion source.

PMID- 20815602
TI  - Low voltage operation of plasma focus.
AB  - Plasma foci of compact sizes and operating with low energies (from tens of joules
      to few hundred joules) have found application in recent years and have attracted
      plasma-physics scientists and engineers for research in this direction. We are
      presenting a low energy and miniature plasma focus which operates from a
      capacitor bank of 8.4 muF capacity, charged at 4.2-4.3 kV and delivering
      approximately 52 kA peak current at approximately 60 nH calculated circuit
      inductance. The total circuit inductance includes the plasma focus inductance.
      The reported plasma focus operates at the lowest voltage among all reported
      plasma foci so far. Moreover the cost of capacitor bank used for plasma focus is
      nearly 20 U.S. dollars making it very cheap. At low voltage operation of plasma
      focus, the initial breakdown mechanism becomes important for operation of plasma
      focus. The quartz glass tube is used as insulator and breakdown initiation is
      done on its surface. The total energy of the plasma focus is approximately 75 J.
      The plasma focus system is made compact and the switching of capacitor bank
      energy is done by manual operating switch. The focus is operated with hydrogen
      and deuterium filled at 1-2 mbar.

PMID- 20815603
TI  - Polycrystalline diamond based detector for Z-pinch plasma diagnosis.
AB  - A detector setup based on polycrystalline chemical-vapor-deposition diamond film
      is developed with great characteristics: low dark current (lower than 60 pA
      within 3 V/mum), fast pulsed response time (rise time: 2-3 ns), flat spectral
      response (3-5 keV), easy acquisition, low cost, and relative large sensitive
      area. The characterizing data on Qiangguang-I accelerator show that this detector
      can satisfy the practical requirements in Z-pinch plasma diagnosis very well,
      which offers a promising prototype for the x-ray detection in Z-pinch diagnosis.

PMID- 20815604
TI  - A new large area lanthanum hexaboride plasma source.
AB  - A new 18x18 cm(2) active area lanthanum hexaboride (LaB(6)) plasma source for use
      in a dc discharge has been developed at UCLA. The cathode consists of four tiled
      LaB(6) pieces indirectly heated to electron emission (1750 degrees C) by a
      graphite heater. A molybdenum mesh anode 33 cm in front of the LaB(6) accelerates
      the electrons, ionizing a fill gas to create a 20x20 cm(2) nearly square plasma.
      The source is run in pulsed operation with the anode biased up to +400 V dc with
      respect to the cathode for up to 100 ms at a 1 Hz repetition rate. Both the
      cathode and anode "float" electrically with respect to the chamber walls. The
      source is placed in a toroidal chamber 2 m wide and 3 m tall with a major radius
      of 5 m. Toroidal and vertical magnetic fields confine the current-free plasma
      which follows the field in a helix. The plasma starts on the bottom of the
      machine and spirals around it up to four times (120 m) and can be configured to
      terminate either on the top wall or on the neutral gas itself. The source
      typically operates with a discharge current up to 250 A in helium making plasmas
      with T(e)<30 eV, T(i)<16 eV, and n(e)<3x10(13) cm(-3) in a background field of
      100 G<B(o)<320 G, giving a magnetized plasma with 0.1<beta<1.

PMID- 20815605
TI  - Compact lanthanum hexaboride hollow cathode.
AB  - A compact lanthanum hexaboride hollow cathode has been developed for space
      applications where size and mass are important and research and industrial
      applications where access for implementation might be limited. The cathode design
      features a refractory metal cathode tube that is easily manufactured,
      mechanically captured orifice and end plates to eliminate expensive e-beam
      welding, graphite sleeves to provide a diffusion boundary to protect the LaB6
      insert from chemical reactions with the refractory metal tube, and several heater
      designs to provide long life. The compact LaB(6) hollow cathode assembly
      including emitter, support tube, heater, and keeper electrode is less than 2 cm
      in diameter and has been fabricated in lengths of 6-15 cm for different
      applications. The cathode has been operated continuously at discharge currents of
      5-60 A in xenon. Slightly larger diameter versions of this design have operated
      at up to 100 A of discharge current.

PMID- 20815606
TI  - Absolute measurements of fast neutrons using yttrium.
AB  - Yttrium is presented as an absolute neutron detector for pulsed neutron sources.
      It has high sensitivity for detecting fast neutrons. Yttrium has the property of
      generating a monoenergetic secondary radiation in the form of a 909 keV gamma-ray
      caused by inelastic neutron interaction. It was calibrated numerically using
      MCNPX and does not need periodic recalibration. The total yttrium efficiency for
      detecting 2.45 MeV neutrons was determined to be f(n) approximately 4.1x10(-4)
      with an uncertainty of about 0.27%. The yttrium detector was employed in the NX2
      plasma focus experiments and showed the neutron yield of the order of 10(8)
      neutrons per discharge.

PMID- 20815607
TI  - High-resolution friction force microscopy under electrochemical control.
AB  - We report the design and development of a friction force microscope for high
      resolution studies in electrochemical environments. The design choices are
      motivated by the experimental requirements of atomic-scale friction measurements
      in liquids. The noise of the system is analyzed based on a methodology for the
      quantification of all the noise sources. The quantitative contribution of each
      noise source is analyzed in a series of lateral force measurements. Normal force
      detection is demonstrated in a study of the solvation potential in a confined
      liquid, octamethylcyclotetrasiloxane. The limitations of the timing resolution of
      the instrument are discussed in the context of an atomic stick-slip measurement.
      The instrument is capable of studying the atomic friction contrast between a bare
      Au(111) surface and a copper monolayer deposited at underpotential conditions in
      perchloric acid.

PMID- 20815608
TI  - Electrostatic actuator probe with curved electrodes for time-of-flight scanning
      force microscopy.
AB  - In this study, we fabricated an electrostatic actuator probe having curved
      electrodes and evaluated its applicability for use in time-of-flight scanning
      force microscopy. In this probe, the end position of a cantilever with a tip is
      switched through electrostatic pull-in effect; the measurement modes can be
      changed between mass analysis and scanning force microscopy (SFM) modes. We
      achieved a large displacement of 400 microm for changing working modes. To
      prevent electrical shortage of the probe and curved electrodes, stoppers were
      formed along the curved electrodes. Because of the pull-in effect, the spring
      constant and resonance frequency increased through stiction of the cantilever to
      the stoppers. Using the fabricated probe, the SFM imaging of a sample featuring a
      2-microm-pitch Au grid was demonstrated.

PMID- 20815609
TI  - An experimental methodology to relate local strain to microstructural texture.
AB  - This paper introduces an experimental methodology for obtaining high resolution
      full-field strain measurements in polycrystalline metals. The (sub)grain level
      resolution of these measurements was indispensable for relating measured strain
      fields to observed microstructure in the material. Microstructural information
      was obtained through electron backscatter diffraction and the optical technique
      of digital image correlation (DIC) was used to acquire full-field deformation
      measurements. By spatially overlaying both sets of results, the effects of
      different microstructural features such as orientation, grain boundary character,
      misorientation between grains, and twin boundaries on material response can be
      quantitatively studied. To obtain the necessary resolution for such measurements,
      the images used in DIC had to be captured at high magnifications. This necessity
      reduces the field of view and constrains the area of interest that can be
      monitored. To address this issue, results from adjacent measurement areas are
      combined together to create a data set with high spatial strain resolution over a
      larger region than can otherwise be observed. The procedure for performing this
      technique is outlined here, along with benefits, drawbacks, possible
      modifications, and example applications of the technique to cyclic plasticity and
      fatigue crack growth.

PMID- 20815610
TI  - A versatile high resolution scanning tunneling potentiometry implementation.
AB  - We have developed a new scanning tunneling potentiometry technique which can-with
      only minor changes of the electronic setup-be easily added to any standard
      scanning tunneling microscope (STM). This extension can be combined with common
      STM techniques such as constant current imaging or scanning tunneling
      spectroscopy. It is capable of performing measurements of the electrochemical
      potential with microvolt resolution. Two examples demonstrate the versatile
      application. First of all, we have determined local variations of the
      electrochemical potential due to charge transport of biased samples down to
      angstrom length scales. Second, with tip and sample at different temperatures we
      investigated the locally varying thermovoltage occurring at the tunneling
      junction. Aside from its use in determining the chemical identity of substances
      at the sample surface our method provides a controlled way to eliminate the
      influence of laterally varying thermovoltages on low-bias constant current
      topographies.

PMID- 20815611
TI  - Single-molecule binding experiments on long time scales.
AB  - We describe an approach for performing single-molecule binding experiments on
      time scales from hours to days, allowing for the observation of slower kinetics
      than have been previously investigated by single-molecule techniques. Total
      internal reflection fluorescence microscopy is used to image the binding of
      labeled ligand to molecules specifically coupled to the surface of an optically
      transparent flow cell. Long-duration experiments are enabled by ensuring
      sufficient positional, chemical, thermal, and image stability. Principal
      components of this experimental stability include illumination timing, solution
      replacement, and chemical treatment of solution to reduce photodamage and
      photobleaching; and autofocusing to correct for spatial drift.

PMID- 20815612
TI  - Fiber optic based system for polarization sensitive spectroscopy of semiconductor
      quantum structures.
AB  - We describe an optical fiber based setup for performing polarization resolved
      magneto-optical spectroscopy measurements under low temperatures ( approximately
      4 K) and high magnetic fields ( approximately 8 T). The measurements are
      performed in a windowless helium Dewar. Circularly polarized light is produced
      inside the Dewar by inserting the polarizing elements between the fiber end and
      the sample. Photoconductivity spectra of a GaAs/AlGaAs multiquantum-well sample
      have been measured over the photon energy range of 1.5-1.7 eV in left and right
      circularly polarized light under crossed magnetic and electric fields. It is
      shown that reversing the direction of magnetic field produces the same spectral
      changes as caused by changing the direction of circular polarization with the
      optical components.

PMID- 20815613
TI  - Nanosecond x-ray Laue diffraction apparatus suitable for laser shock compression
      experiments.
AB  - We have used nanosecond bursts of x-rays emitted from a laser-produced plasma,
      comprised of a mixture of mid-Z elements, to produce a quasiwhite-light spectrum
      suitable for performing Laue diffraction from single crystals. The laser-produced
      plasma emits x-rays ranging in energy from 3 to in excess of 10 keV, and is
      sufficiently bright for single shot nanosecond diffraction patterns to be
      recorded. The geometry is suitable for the study of laser-shocked crystals, and
      single-shot diffraction patterns from both unshocked and shocked silicon crystals
      are presented.

PMID- 20815614
TI  - Simultaneous measurement of circular dichroism and Faraday rotation at terahertz
      frequencies utilizing electric field sensitive detection via polarization
      modulation.
AB  - A far-infrared system measures the full complex Faraday angle, the rotation as
      well as the ellipticity, with an unprecedented accuracy of 10 microrad/T. The
      system operates on several far-infrared laser lines in the spectral range from
      0.3 to 6 THz and produces results as a continuous function of temperature from 10
      to 310 K and applied fields between +/-8 T. Performance of the instrument is
      demonstrated by measurements on a GaAs two-dimensional electron gas
      heterostructure and Bi(2)Sr(2)CaCu(2)O(8+x) single crystal.

PMID- 20815615
TI  - Identification of a deuterated alkanethiol inserted in a hydrogenated alkanethiol
      self-assembled monolayer by mapping of an inelastic tunneling signal.
AB  - We show an experimental technique for visualizing distributions of vibrational
      modes of molecules through mapping of an inelastic tunneling signal with a
      scanning tunneling microscope. A topographic information and d(2)I/dV(2) signal
      processed by a lock-in amplifier were simultaneously imaged, where the feedback
      loop for the tunneling gap was engaged and a modulation voltage was superimposed
      to the gap voltage. The current signal used for the tunneling gap control was
      tuned by the filtering in order to minimize the response of the feedback loop
      caused by the modulation voltage. The effectiveness of this technique was
      demonstrated for a self-assembled monolayer composed of a mixture of normal and
      deuterated hexanethiol molecules, where both molecules have the same molecular
      length and the former was embedded in the matrix of the latter. Two types of
      molecules were successfully discriminated by chemical properties.

PMID- 20815616
TI  - A pair of concentric capillaries as an interface for gas chromatography and
      supersonic jet/multiphoton ionization/mass spectrometry.
AB  - A pair of concentric capillaries was developed to mix helium, which was used as
      the carrier gas for gas chromatography, with argon for efficient molecular
      cooling by supersonic jet expansion. A simple instrument was constructed for the
      evaluation of nozzle diameter using the Hagen-Poiseuille equation. The effects of
      nozzle diameter, type of expansion gas, flow rate, and the distance from the
      nozzle to the observation region were investigated. Mixing argon gas with the
      carrier gas helium resulted in efficient molecular cooling from 30 to 10 K and
      the complete disappearance of the background signal from the multiphoton
      ionization spectrum. Consequently, the spectral selectivity was significantly
      improved and the nozzle was successfully applied to isomer-selective analysis of
      dichlorotoluenes. Since the dead volume in the nozzle was negligible, it was
      suitable as an interface for gas chromatography and supersonic jet/multiphoton
      ionization/mass spectrometry.

PMID- 20815617
TI  - Microbial population dynamics by digital in-line holographic microscopy.
AB  - Measurements of population dynamics are ubiquitous in experiments with
      microorganisms. Studies with microbes elucidating adaptation, selection, and
      competition rely on measurements of changing populations in time. Despite this
      importance, quantitative methods for measuring population dynamics
      microscopically, with high time resolution, across many replicates remain
      limited. Here we present a new noninvasive method to precisely measure microbial
      spatiotemporal population dynamics based on digital in-line holographic (DIH)
      microscopy. Our inexpensive, replicate DIH microscopes imaged hundreds of
      swimming algae in three dimensions within a volume of several microliters on a
      time scale of minutes over periods of weeks.

PMID- 20815618
TI  - Design of a standalone-type beryllium vessel for high-pressure protein
      crystallography.
AB  - A standalone-type beryllium (Be) high-pressure crystallography vessel has been
      developed. Using a coupler-joint unit and a pressure valve, we could keep the
      pressure in the vessel constant at 100+/-1 MPa for more than 24 h without
      connecting to a pressure-generating apparatus. Diffraction spots of a glucose
      isomerase (GI) crystal under 100 MPa were collected using the vessel and a
      rotating copper-anode in-house x-ray generator (0.8 kW). We successfully
      collected a 2.0 A resolution data set of a 0.5 mm size GI crystal in an aqueous
      solution at 100 MPa.

PMID- 20815619
TI  - New portable sensor system for rotational seismic motion measurements.
AB  - A new mechanical sensor system for recording the rotation of ground velocity has
      been constructed. It is based on measurements of differential motions between
      paired sensors mounted along the perimeter of a rigid (undeformable) disk. The
      elementary sensors creating the pairs are sensitive low-frequency geophones
      currently used in seismic exploration to record translational motions. The main
      features of the new rotational seismic sensor system are flat characteristics in
      the wide frequency range from 1 to 200 Hz and sensitivity limit of the order of
      10(-8) rad/s. Notable advantages are small dimensions, portability, easy
      installation and operation in the field, and the possibility of calibrating the
      geophones in situ simultaneously with the measurement. An important feature of
      the instrument is that it provides records of translational seismic motions
      together with rotations, which allows many important seismological applications.
      We have used the new sensor system to record the vertical rotation velocity due
      to a small earthquake of M(L)=2.2, which occurred within the earthquake swarm in
      Western Bohemia in autumn 2008. We found good agreement of the rotation record
      with the transverse acceleration as predicted by theory. This measurement
      demonstrates that this device has a much wider application than just to
      prospecting measurements, for which it was originally designed.

PMID- 20815620
TI  - On the magnetic field near the center of Helmholtz coils.
AB  - We develop a series expansion for the calculation of the magnetic field near the
      center of Helmholtz coils and apply the result to a magnet of our design. Our
      analysis considers geometric details of the coils, the magnetic properties of the
      form and windings, conductor insulation effects, and several winding
      imperfections. We also consider the relaxation of coil symmetry which happens
      when the mean radius of each coil and the coil midplane separation distance are
      unequal. We compute the field uniformity near the coil's center for three cases,
      including one where axial symmetry remains but geometric imperfections of the
      order of 10(-3) of the coil "radius" exist.

PMID- 20815621
TI  - Time domain characterization of magnetoelastic sensors: A pulse method for
      resonance frequency determination.
AB  - This paper presents a pulse method for determination of resonance frequency of
      magnetoelastic sensors. The method eliminates the bias field that is necessary in
      previous methods and also allows fast and accurate detection. The stability tests
      of the system show an average standard deviation of 129 Hz and an average drift
      of -10.4 Hz/h. This system allows simultaneous detection of two sensors. A
      simulation of the operation of one and two sensors was shown to be very similar
      to the real data plots from the test system. Real tests have shown that adding a
      second sensor does not affect the resonance frequency of the first sensor. The
      effect of pulse magnetic field on the characteristics of the resonance signal,
      including resonance frequency, amplitude, and Q-value of frequency domain signal,
      has been studied and real time detection using magnetoelastic sensors was
      demonstrated in a flowing system.

PMID- 20815622
TI  - Dynamic ellipsometry study on curved thin films at pendent droplet surfaces.
AB  - This paper describes the construction of an apparatus that detects the dynamic
      thickness/reflective-index changes of the curved thin films on the pendent
      droplet surfaces. The apparatus was constructed by integrating two well
      established techniques: null ellipsometry and the pendent drop shape analysis
      system. The shape analysis system is used to precisely control the height of the
      objective pendent droplets. This allows the laser beam of ellipsometry to be
      continually locked in the exact bottom position of the pendent droplets. Such an
      arrangement facilitates the dynamic investigation of the film thickness as well
      as the continual monitoring of the surface tension.

PMID- 20815623
TI  - Portable high pressure sapphire anvil cell for gas hydrates research.
AB  - A sapphire anvil cell, a portable system having a sample volume of about 400
      mm(3) (Phi8x8 mm), has been developed for gas hydrates research under high
      pressure. As both pressure and temperature of the sample can be precisely
      monitored in real time, the system has significant advantages for gas hydrates
      research at the pressure range of 1-40 MPa and temperature range of 250-350 K. We
      have applied this sapphire anvil cell system to carry out experiments for
      investigating the formation and dissociation of CO(2) hydrate. In addition, the
      developed sapphire anvil cell can be used for in situ thermal, electric,
      ultrasonic, visible light, Raman, and IR measurements.

PMID- 20815624
TI  - Helium cryostat for experimental study of natural turbulent convection.
AB  - Published experiments on natural turbulent convection in cryogenic (4)He gas show
      contradictory results in the values of Rayleigh number (Ra) higher than 10(11).
      This paper describes a new helium cryostat with a cylindrical cell designed for
      the study of the dependence of the Nusselt number (Nu) on the Rayleigh number (up
      to Ra approximately 10(15)) in order to help resolve the existing controversy
      among published experimental results. The main part of the cryostat is a
      cylindrical convection cell of 300 mm in diameter and up to 300 mm in height. The
      cell is designed for measurement of heat transfer by natural convection at
      pressures ranging from 100 Pa to 250 kPa and at temperatures between 4.2 and 12
      K. Parasitic heat fluxes into the convection medium are minimized by using thin
      sidewalls of the bottom and top parts of the cell. The exchangeable central part
      of the cell enables one to modify the cell geometry.

PMID- 20815625
TI  - High-speed tracking control of piezoelectric actuators using an ellipse-based
      hysteresis model.
AB  - In this paper, an ellipse-based mathematic model is developed to characterize the
      rate-dependent hysteresis in piezoelectric actuators. Based on the proposed
      model, an expanded input space is constructed to describe the multivalued
      hysteresis function H[u](t) by a multiple input single output (MISO) mapping
      Gamma:R(2)-->R. Subsequently, the inverse MISO mapping Gamma(
      1)(H[u](t),H[u](t);u(t)) is proposed for real-time hysteresis compensation. In
      controller design, a hybrid control strategy combining a model-based feedforward
      controller and a proportional integral differential (PID) feedback loop is used
      for high-accuracy and high-speed tracking control of piezoelectric actuators. The
      real-time feedforward controller is developed to cancel the rate-dependent
      hysteresis based on the inverse hysteresis model, while the PID controller is
      used to compensate for the creep, modeling errors, and parameter uncertainties.
      Finally, experiments with and without hysteresis compensation are conducted and
      the experimental results are compared. The experimental results show that the
      hysteresis compensation in the feedforward path can reduce the hysteresis-caused
      error by up to 88% and the tracking performance of the hybrid controller is
      greatly improved in high-speed tracking control applications, e.g., the root-mean
      square tracking error is reduced to only 0.34% of the displacement range under
      the input frequency of 100 Hz.

PMID- 20815626
TI  - Contactless measurement of critical current of high temperature superconductor
      tape by magnetic circuit.
AB  - A method based on the principle of the magnetic circuit is proposed and realized
      for contactless measurement of critical current (I(c)) of high temperature
      superconductor tapes. This method has two unique features: first, it eliminates
      noises caused by mechanical fluctuations and thus makes high speed and high
      stability measurement possible and second, adapts for both
      Bi(2)Si(2)Ca(2)Cu(3)O(x) (Bi2223) and YBa(2)Cu(3)O(7-x) (YBCO) tape, which even
      has a magnetic substrate. Theoretical analysis is given and an apparatus for the
      reel-to-reel measurement has been constructed, by which continuous inspection of
      I(c) uniformity of YBCO and Bi2223 tapes measured at different speeds is
      reported.

PMID- 20815627
TI  - Design of microcontroller based system for automation of streak camera.
AB  - A microcontroller based system has been developed for automation of the S-20
      optical streak camera, which is used as a diagnostic tool to measure ultrafast
      light phenomenon. An 8 bit MCS family microcontroller is employed to generate all
      control signals for the streak camera. All biasing voltages required for various
      electrodes of the tubes are generated using dc-to-dc converters. A high voltage
      ramp signal is generated through a step generator unit followed by an integrator
      circuit and is applied to the camera's deflecting plates. The slope of the ramp
      can be changed by varying values of the capacitor and inductor. A programmable
      digital delay generator has been developed for synchronization of ramp signal
      with the optical signal. An independent hardwired interlock circuit has been
      developed for machine safety. A LABVIEW based graphical user interface has been
      developed which enables the user to program the settings of the camera and
      capture the image. The image is displayed with intensity profiles along
      horizontal and vertical axes. The streak camera was calibrated using nanosecond
      and femtosecond lasers.

PMID- 20815628
TI  - Core level photoionization on free sub-10-nm nanoparticles using synchrotron
      radiation.
AB  - A novel instrument is presented, which permits studies on singly charged free
      nanoparticles in the diameter range from 1 to 30 nm using synchrotron radiation
      in the soft x-ray regime. It consists of a high pressure nanoparticle source, a
      high efficiency nanoparticle beam inlet, and an electron time-of-flight
      spectrometer suitable for probing surface and bulk properties of free, levitated
      nanoparticles. We show results from x-ray photoelectron spectroscopy study near
      the Si L(3,2)-edge on 8.2 nm SiO(2) particles prepared in a nanoparticle beam.
      The possible use of this apparatus regarding chemical reactions on the surface of
      nanometer-sized particles is highlighted. This approach has the potential to be
      exploited for process studies on heterogeneous atmospheric chemistry.

PMID- 20815629
TI  - Development of an x-ray prism for analyzer based imaging systems.
AB  - Analyzer crystal based imaging techniques such as diffraction enhanced imaging
      (DEI) and multiple imaging radiography (MIR) utilize the Bragg peak of perfect
      crystal diffraction to convert angular changes into intensity changes. These x
      ray techniques extend the capability of conventional radiography, which derives
      image contrast from absorption, by providing large intensity changes for small
      angle changes introduced from the x-ray beam traversing the sample. Objects that
      have very little absorption contrast may have considerable refraction and
      ultrasmall angle x-ray scattering contrast improving visualization and extending
      the utility of x-ray imaging. To improve on the current DEI technique an x-ray
      prism (XRP) was designed and included in the imaging system. The XRP allows the
      analyzer crystal to be aligned anywhere on the rocking curve without physically
      moving the analyzer from the Bragg angle. By using the XRP to set the rocking
      curve alignment rather than moving the analyzer crystal physically the needed
      angle sensitivity is changed from submicroradians for direct mechanical movement
      of the analyzer crystal to tens of milliradians for movement of the XRP angle.
      However, this improvement in angle positioning comes at the cost of absorption
      loss in the XRP and depends on the x-ray energy. In addition to using an XRP for
      crystal alignment it has the potential for scanning quickly through the entire
      rocking curve. This has the benefit of collecting all the required data for image
      reconstruction in a single measurement thereby removing some problems with motion
      artifacts which remain a concern in current DEI/MIR systems especially for living
      animals.

PMID- 20815630
TI  - Note: Multiscale scanning probe microscopy.
AB  - Combining the nanoscopic and macroscopic worlds is a serious challenge common to
      numerous scientific fields, from physics to biology. In this paper, we
      demonstrate nanometric resolution over a millimeter range by means of atomic
      force microscopy using metrological stage. Nanometric repeatability and
      millimeter range open up the possibility of probing components and materials
      combining multiscale properties i.e., engineered nanomaterials. Multiscale
      probing is not limited to atomic-force microscopy and can be extended to any type
      of scanning probe technique in nanotechnology, including piezoforce microscopy,
      electrostatic-force microscopy, and scanning near-field optical microscopy.

PMID- 20815631
TI  - Note: Dead time causes and correction method for single photon avalanche diode
      devices.
AB  - Single photon avalanche diode (SPAD) is the new generation of Geiger-Muller (GM)
      detectors, developed with semiconductor technology, and able to detect single
      photons, mainly in visible range. In this work we study the signal generation
      process and the dead time (DT) mechanisms of the device under a constant light
      regime. According to our results, it is possible to discriminate low rate signals
      from afterpulse and noise production and, moreover, to overcome the saturation
      effect due to the dead time losses. Starting from hybrid DT model [S. H. Lee and
      R. P. Gardner, Appl. Radiat. Isot. 53, 731 (2000)] we have been able to evaluate
      the real amount of incident photon rate up to 10(7) cps using a passive quenched
      device with 0.97 mus total dead time. In this way the passive quenched SPAD
      achieves the same performance of the active quenched one showing that relatively
      complex data analysis and complex device implementation are comparable solutions
      for constant light measurement. We also analyze some effects, lacking in GM
      counter, which should be introduced in the analysis of semiconductor device, as
      afterpulse, reduced photon detection efficiency, and noise production.

PMID- 20815632
TI  - Note: A modular and robust continuous supersonic expansion discharge source.
AB  - A direct current discharge has been coupled with a continuous supersonic
      expansion to provide a source of rotationally cold molecular ions for gas phase
      spectroscopy. Constructed primarily of machinable ceramic and stainless steel,
      this source design is modular, customizable, and robust. Its performance has been
      assessed by recording transitions within the nu(2) fundamental band of H(3) (+)
      using cavity ringdown spectroscopy to determine the rotational temperature of
      ions produced in the free-jet expansion. Temperature and column density were
      recorded as a function of discharge current as the source was operated over a
      period of 200 h. Observed temperatures ranged between 50-110 K, and the ion
      column densities between 8x10(10) and 2x10(12) cm(-2).

PMID- 20815633
TI  - Note: Fixture for characterizing electrochemical devices in-operando in
      traditional vacuum systems.
AB  - We describe a fixture that allows electrochemical devices to be studied under
      electrical bias in the type of vacuum systems commonly used in surface science.
      Three spring-loaded probes provide independent contacts for device operation and
      the characterization in vacuum or under in situ conditions with reactive gases.
      We document the robustness of the electrical contacts over large temperature
      changes and their reliability for conventional electrochemical measurements such
      as impedance spectroscopy. The optical access provided to the device enables the
      analysis by many techniques, as we demonstrate using x-ray photoelectron
      spectroscopy to measure local electrical potentials on a solid-oxide electrolyte
      device operating at high temperature in near-ambient pressure.

PMID- 20815635
TI  - A biomechanical investigation of ankle injury under excessive external foot
      rotation in the human cadaver.
AB  - Numerous studies on the mechanisms of ankle injury deal with injuries to the
      syndesmosis and anterior ligamentous structures but a previous sectioning study
      also describes the important role of the posterior talofibular ligament (PTaFL)
      in the ankle's resistance to external rotation of the foot. It was hypothesized
      that failure level external rotation of the foot would lead to injury of the
      PTaFL. Ten ankles were tested by externally rotating the foot until gross injury.
      Two different frequencies of rotation were used in this study, 0.5 Hz and 2 Hz.
      The mean failure torque of the ankles was 69.5+/-11.7 Nm with a mean failure
      angle of 40.7+/-7.3 degrees . No effects of rotation frequency or flexion angle
      were noted. The most commonly injured structure was the PTaFL. Visible damage to
      the syndesmosis only occurred in combination with fibular fracture in these
      experiments. The constraint of the subtalar joint in the current study may have
      affected the mechanics of the foot and led to the resultant strain in the PTaFL.
      In the real world, talus rotations may be affected by athletic footwear that may
      influence the location and potential for an ankle injury under external rotation
      of the foot.

PMID- 20815636
TI  - Anatomical study of the radius and center of curvature of the distal femoral
      condyle.
AB  - In this anatomical study, the anteroposterior curvature of the surface of 16
      cadaveric distal femurs was examined in terms of radii and center point. Those
      two parameters attract high interest due to their significance for total knee
      arthroplasty. Basically, two different conclusions have been drawn in foregoing
      studies: (1) The curvature shows a constant radius and (2) the curvature shows a
      variable radius. The investigations were based on a new method combining three
      dimensional laser-scanning and planar geometrical analyses. This method is aimed
      at providing high accuracy and high local resolution. The high-precision laser
      scanning enables the exact reproduction of the distal femurs-including their
      cartilage tissue-as a three-dimensional computer model. The surface curvature was
      investigated on intersection planes that were oriented perpendicularly to the
      surgical epicondylar line. Three planes were placed at the central part of each
      condyle. The intersection of either plane with the femur model was approximated
      with the help of a b-spline, yielding three b-splines on each condyle. The radii
      and center points of the circles, approximating the local curvature of the b
      splines, were then evaluated. The results from all three b-splines were averaged
      in order to increase the reliability of the method. The results show the
      variation in the surface curvatures of the investigated samples of condyles.
      These variations are expressed in the pattern of the center points and the radii
      of the curvatures. The standard deviations of the radii for a 90 deg arc on the
      posterior condyle range from 0.6 mm up to 5.1 mm, with an average of 2.4 mm
      laterally and 2.2 mm medially. No correlation was found between the curvature of
      the lateral and medial condyles. Within the range of the investigated 16 samples,
      the conclusion can be drawn that the condyle surface curvature is not constant
      and different for all specimens when viewed along the surgical epicondylar axis.
      For the portion of the condylar surface that articulates with the tibia during
      knee flexion-extension, the determined center points approximate the location of
      the centers of rotation. The results suggest that the concept of a fixed flexion
      extension axis is not applicable for every specimen.

PMID- 20815637
TI  - Nonthermal irreversible electroporation for tissue decellularization.
AB  - Tissue scaffolding is a key component for tissue engineering, and the
      extracellular matrix (ECM) is nature's ideal scaffold material. A conceptually
      different method is reported here for producing tissue scaffolds by
      decellularization of living tissues using nonthermal irreversible electroporation
      (NTIRE) pulsed electrical fields to cause nanoscale irreversible damage to the
      cell membrane in the targeted tissue while sparing the ECM and utilizing the
      body's host response for decellularization. This study demonstrates that the
      method preserves the native tissue ECM and produces a scaffold that is functional
      and facilitates recellularization. A two-dimensional transient finite element
      solution of the Laplace and heat conduction equations was used to ensure that the
      electrical parameters used would not cause any thermal damage to the tissue
      scaffold. By performing NTIRE in vivo on the carotid artery, it is shown that in
      3 days post NTIRE the immune system decellularizes the irreversible
      electroporated tissue and leaves behind a functional scaffold. In 7 days, there
      is evidence of endothelial regrowth, indicating that the artery scaffold
      maintained its function throughout the procedure and normal recellularization is
      taking place.

PMID- 20815638
TI  - Effects of anterior shear displacement rate on the structural properties of the
      porcine cervical spine.
AB  - While the individual tissues of the vertebral joint demonstrate viscoelastic
      properties, the global viscoelastic properties of the lumbar vertebral joint are
      not well established. This study investigated how changes in displacement rate
      influenced the mechanical response of the porcine cervical spine (a surrogate or
      model for the human lumbar spine) exposed to acute anterior shear failure
      loading. Thirty porcine cervical spine specimens (15 C3-C4 and 15 C5-C6) were
      placed under a 1600 N compressive load and subsequently loaded in anterior shear
      to failure at one of three randomly assigned displacement rates (1 mm/s, 4 mm/s,
      or 16 mm/s). Ultimate anterior shear force, ultimate displacement, average
      stiffness, and energy stored until failure were calculated. Load rate in the
      elastic region was also calculated to compare the load rates used in this study
      to those used in previous studies. Changes in displacement rate affected the C3
      C4 and C5-C6 specimens differently. C5-C6 specimens tested at 16 mm/s had an
      ultimate force that was 28% and 23% higher than at 1 (p=0.0215) and 4 mm/s
      (p=0.0461), respectively. The average stiffness to failure of the C5-C6 specimens
      tested at 16 mm/s was 52% higher than at 4 mm/s (p=0.0289). No such differences
      were found for the C3-C4 specimens. An increase in the anterior shear
      displacement rate did not necessarily demonstrate viscoelasticity of the
      vertebral joint. Specimen intervertebral levels were affected differently by
      changes in anterior shear displacement rate, which may have been a result of
      anatomical and postural differences between the two levels. Future studies should
      further investigate the effect of displacement rate on the spine and the
      inconsistencies between different specimen levels.

PMID- 20815639
TI  - Outflow conditions for image-based hemodynamic models of the carotid bifurcation:
      implications for indicators of abnormal flow.
AB  - Computational fluid dynamics (CFD) models have become very effective tools for
      predicting the flow field within the carotid bifurcation, and for understanding
      the relationship between local hemodynamics, and the initiation and progression
      of vascular wall pathologies. As prescribing proper boundary conditions can
      affect the solutions of the equations governing blood flow, in this study, we
      investigated the influence to assumptions regarding the outflow boundary
      conditions in an image-based CFD model of human carotid bifurcation. Four
      simulations were conducted with identical geometry, inlet flow rate, and fluid
      parameters. In the first case, a physiological time-varying flow rate partition
      at branches along the cardiac cycle was obtained by coupling the 3D model of the
      carotid bifurcation at outlets with a lumped-parameter model of the downstream
      vascular network. Results from the coupled model were compared with those
      obtained by imposing three fixed flow rate divisions (50/50, 60/40, and 70/30)
      between the two branches of the isolated 3D model of the carotid bifurcation.
      Three hemodynamic wall parameters were considered as indicators of vascular wall
      dysfunction. Our findings underscore that the overall effect of the assumptions
      done in order to simulate blood flow within the carotid bifurcation is mainly in
      the hot-spot modulation of the hemodynamic descriptors of atherosusceptible
      areas, rather than in their distribution. In particular, the more physiological,
      time-varying flow rate division deriving from the coupled simulation has the
      effect of damping wall shear stress (WSS) oscillations (differences among the
      coupled and the three fixed flow partition models are up to 37.3% for the
      oscillating shear index). In conclusion, we recommend to adopt more realistic
      constraints, for example, by coupling models at different scales, as in this
      study, when the objective is the outcome prediction of alternate therapeutic
      interventions for individual patients, or to test hypotheses related to the role
      of local fluid dynamics and other biomechanical factors in vascular diseases.

PMID- 20815640
TI  - A neurogenetic approach to a multiobjective design optimization of spinal pedicle
      screws.
AB  - A pedicle screw fixation has been widely used to treat spinal diseases. Clinical
      reports have shown that the weakest part of the spinal fixator is the pedicle
      screw. However, previous studies have only focused on either screw breakage or
      screw loosening. There have been no studies that have addressed the
      multiobjective design optimization of the pedicle screws. The multiobjective
      optimization methodology was applied and it consisted of finite element method,
      Taguchi method, artificial neural networks, and genetic algorithms. Three
      dimensional finite element models for both the bending strength and the pullout
      strength of the pedicle screw were first developed and arranged on an L(25)
      orthogonal array. Then, artificial neural networks were used to create two
      objective functions. Finally, the optimum solutions of the pedicle screws were
      obtained by genetic algorithms. The results showed that the optimum designs had
      higher bending and pullout strengths compared with commercially available screws.
      The optimum designs of pedicle screw revealed excellent biomechanical
      performances. The neurogenetic approach has effectively decreased the time and
      effort required for searching for the optimal designs of pedicle screws and has
      directly provided the selection information to surgeons.

PMID- 20815641
TI  - Acute recovery of patellar tendon from heat-induced shrinkage and its inhibition
      by cross-linking.
AB  - There are two important factors that accompany heat-induced shrinkage of
      collagenous tissues: mechanical property degradation and partial recovery from
      the shrunken length (elongation) upon returning to room temperature (defined here
      as acute recovery). These undesirable factors reduce the efficacy of thermal
      therapies. We applied chemical cross-linking adjuvant to thermal treatment on New
      Zealand White rabbit patellar tendon complexes to explore the feasibility of
      reducing the impact of these undesirable side-effects. Our results have shown
      that with exposure to 0.5% w/v glutaraldehyde solution during heating, the
      recovery response of the patellar tendon tissue was decreased, and the mechanical
      properties of the tissue were significantly improved.

PMID- 20815642
TI  - Elasticity of the porcine lens capsule as measured by osmotic swelling.
AB  - As an alternative to purely mechanical methods, optical tracking of passive
      osmotic swelling was used to assess mechanical properties of the porcine lens
      capsule. A simple model was developed accounting for the permeability of the lens
      fiber cells and capsule to water, the concentration of fixed charges in the fiber
      cells, and the capsule's resistance to the swelling of fiber cells. Fitting the
      model solution to experimental data provided an estimate of the elastic modulus
      of the lens capsule under the assumption of linear isotropic elasticity. The
      calculated elastic modulus at a fixed charge density of 20 mol m(-3) was 2.0+/
      0.5 MPa (mean+/-95% confidence interval; n=15) for 0.1% saline solution, 0.64+/
      0.3 MPa (n=10) for 0.2% saline solution, and 0.28+/-0.5 MPa (n=6) for 0.5% saline
      solution. These values are comparable to previously reported moduli of elasticity
      for the porcine lens capsule at small strains (<10%), and the slight increase
      with hypotonicity is consistent with the nonlinear mechanical behavior of the
      lens capsule. Although limited by being a single measurement on a heterogeneous
      tissue, osmotic swelling provides a quantitative assessment of the stiffness of
      the lens capsule without requiring dissection or manipulation of the lens. Thus,
      the new method could be useful for small animal models.

PMID- 20815643
TI  - Sensitivity of CFD based hemodynamic results in rabbit aneurysm models to
      idealizations in surrounding vasculature.
AB  - Computational fluid dynamics (CFD) studies provide a valuable tool for evaluating
      the role of hemodynamics in vascular diseases such as cerebral aneurysms and
      atherosclerosis. However, such models necessarily only include isolated segments
      of the vasculature. In this work, we evaluate the influence of geometric
      approximations in vascular anatomy on hemodynamics in elastase induced saccular
      aneurysms in rabbits. One representative high aspect ratio (AR-height/neck width)
      aneurysm and one low AR aneurysm were created at the origin of the right common
      carotid artery in two New Zealand white rabbits. Three-dimensional (3D)
      reconstructions of the aneurysm and surrounding arteries were created using 3D
      rotational angiographic data. Five models with varying extents of neighboring
      vasculature were created for both the high and low AR cases. A reference model
      included the aneurysm sac, left common carotid artery (LCCA), aortic arch, and
      downstream trifurcation/quadrification. Three-dimensional, pulsatile CFD studies
      were performed and streamlines, wall shear stress (WSS), oscillatory shear index,
      and cross sectional velocity were compared between the models. The influence of
      the vascular domain on intra-aneurysmal hemodynamics varied between the low and
      high AR cases. For the high AR case, even a simple model including only the
      aneurysm, a small section of neighboring vasculature, and simple extensions
      captured the main features of the steamline and WSS distribution predicted by the
      reference model. However, the WSS distribution in the low AR case was more
      strongly influenced by the extent of vasculature. In particular, it was necessary
      to include the downstream quadrification and upstream LCCA to obtain good
      predictions of WSS. The findings in this work demonstrate the accuracy of CFD
      results can be compromised if insufficient neighboring vessels are included in
      studies of hemodynamics in elastase induced rabbit aneurysms. Consideration of
      aspect ratio, hemodynamic parameters of interest, and acceptable magnitude of
      error when selecting the vascular domain will increase reliability of the results
      while decreasing computational time.

PMID- 20815644
TI  - An examination of the influence of strain rate on subfailure mechanical
      properties of the annulus fibrosus.
AB  - Disk herniation is often considered a cumulative injury in that repetitive stress
      on the posterior annulus can result in the nucleus pulposus penetrating the
      annulus fibrosus and eventually extruding posteriorly. Further, it has been
      documented that the nucleus pulposus works its way through the annulus through
      clefts, which form as a result of repetitive tensile strain. The annulus fibrosus
      is viscoelastic in nature and therefore could express different mechanical
      responses to applied strain at varying rates. Other viscoelastic tissues,
      including tendons and ligaments, have shown altered mechanical responses to
      different rates of applied strain, but the response of the annulus to varying
      rates of strain is largely unknown. The present study examined the mechanical
      properties of 20 two-layered samples of porcine annulus fibrosus tissue at three
      distinct rates of applied 20% biaxial strain (20% strain over 20 s (slow), over
      10 s (medium), and over 5 s (fast)); these three rates are considered applicable
      to nontraumatic loading. No differences in the stiffness or maximum stress in
      each of the two directions of applied strain were observed between the three
      strain rates. Specifically, the average (standard deviation) moduli calculated at
      the fast, medium, and slow rates, respectively, in the axial direction were 7.42
      MPa (6.06), 7.77 MPa (6.61), and 7.63 MPa (6.67) and 8.22 MPa (8.4), 8.63 MPa
      (9.00), and 8.49 MPa (8.69) in the circumferential direction. The maximum stress
      values reached during the fast, medium, and slow rates, respectively, in the
      axial direction were 0.40 (0.36) MPa, 0.40 (0.36) MPa, and 0.39 (0.35) MPa and
      0.45 (0.47) MPa, 0.44 (0.46) MPa, and 0.43 (0.46) MPa in the circumferential
      direction. At submaximal strain magnitudes over a range of nontraumatic rates
      likely to result in clefts in the annulus and potentially leading to disk
      herniation, any strain rate dependence is not significant.

PMID- 20815645
TI  - Numerical modeling of stress in stenotic arteries with microcalcifications: a
      micromechanical approximation.
AB  - Most finite element models of atherosclerotic arteries do not account for the
      heterogeneity of the plaque constituents at the microscale. Failure of plaque
      lesions has been shown to be a local event, linked to stress concentrations
      caused by cap thinning, inflammation, macroscopic heterogeneity, and recently,
      the presence of microcalcifications. There is growing evidence that
      microcalcifications exist in the fibrous cap of plaque lesions. However, their
      role is not yet fully understood. The goal of the present work is to investigate
      the effects of localized regions of microcalcifications on the stress field of
      atherosclerotic plaque caps in a section of carotid artery. This is achieved by
      performing finite element simulations of three-dimensional fluid-structure
      interaction models. The material response in the region of microcalcification is
      modeled using a combination of finite elements, homogenization theory, and a
      stress concentration function that approximates the average local stresses in the
      fibrous tissue and microcalcification phases. The results indicate that the
      circumferential stress in the fibrous tissue phase increases as the volume
      fraction of microcalcifications is increased, and that the stress exceeds a
      critical threshold when the fibrous cap thickness is decreased. Furthermore, the
      presence of the microcalcifications significantly influences the distribution of
      stress by shifting the maximum circumferential stress away from the cap
      shoulders, where failure is most common when the effective region of
      microcalcification is located at the center of the cap. This is a possible
      explanation of why 40% of plaque ruptures occur away from the shoulder region of
      the cap.

PMID- 20815646
TI  - Quantifying ligament cross-sectional area via molding and casting.
AB  - Ligament cross-sectional areas are difficult to determine because ligaments are
      soft tissues, can be very short, and may be deep between bones. However, accurate
      measurements are required for determining the material properties from mechanical
      testing. Many techniques have been tried, but most suffer from one or more of the
      following: tissue deformation, tissue destruction, submersion of the tissue in
      saline, the need for a clear line of site, the inability to detect concavities,
      or poorly defined cross-sectional perimeters. Molding techniques have been used
      but have been limited by material issues such as large shrinkages, the inability
      to capture small detail, or the need to destroy the mold to remove the ligament.
      In this study, we developed a suitable molding and casting technique without
      systematic shrinkage that could accurately capture the odd shapes and concavities
      of foot and ankle ligaments with small clearances between bones. Metal rods of
      1.62 mm, 2.90 mm, 3.18 mm, and 9.43 mm in diameter were molded using a liquid
      silicone rubber and cast with polyurethane. The effect of cutting the mold for
      specimen removal was investigated, and similar tests were done in the presence of
      saline. Image analysis software was used to determine the cross-sectional areas
      from photographs of cut castings. In addition, four different ligaments (each
      n=5) were dissected, molded, and cast. The cross-sectional area of each ligament
      was obtained. The maximum difference in area for all cases was 2.00%, with the
      majority being less than 1.00%; the overall root mean square error was 0.334
      mm(2) or 0.97%. Neither cutting the mold for specimen removal nor the presence of
      saline affected the cross-sectional area of the castings. Various representative
      foot and ankle ligaments were also molded and cast to capture fine detail of the
      ligament midsubstance including concavities. We have developed a method of
      measuring ligament cross-sectional area that can overcome the limitations of
      other area measurement techniques, while accounting for the complicated anatomy
      of the bones of the foot. The method was validated using metal rods of known
      diameters, and a representative set foot ligaments (N=20) was analyzed.

PMID- 20815647
TI  - Viscoelastic and biomechanical properties of osteochondral tissue constructs
      generated from graded polycaprolactone and beta-tricalcium phosphate composites.
AB  - The complex micro-/nanostructure of native cartilage-to-bone insertion exhibits
      gradations in extracellular matrix components, leading to variations in the
      viscoelastic and biomechanical properties along its thickness to allow for smooth
      transition of loads under physiological movements. Engineering a realistic tissue
      for osteochondral interface would, therefore, depend on the ability to develop
      scaffolds with properly graded physical and chemical properties to facilitate the
      mimicry of the complex elegance of native tissue. In this study, polycaprolactone
      nanofiber scaffolds with spatially controlled concentrations of beta-tricalcium
      phosphate nanoparticles were fabricated using twin-screw extrusion
      electrospinning process and seeded with MC3T3-E1 cells to form osteochondral
      tissue constructs. The objective of the study was to evaluate the linear
      viscoelastic and compressive properties of the native bovine osteochondral tissue
      and the tissue constructs formed in terms of their small-amplitude oscillatory
      shear, unconfined compression, and stress relaxation behavior. The native tissue,
      engineered tissue constructs, and unseeded scaffolds exhibited linear
      viscoelastic behavior for strain amplitudes less than 0.1%. Both native tissue
      and engineered tissue constructs demonstrated qualitatively similar gel-like
      behavior as determined using linear viscoelastic material functions. The normal
      stresses in compression determined at 10% strain for the unseeded scaffold, the
      tissue constructs cultured for four weeks, and the native tissue were 0.87+/-0.08
      kPa, 3.59+/-0.34 kPa, and 210.80+/-8.93 kPa, respectively. Viscoelastic and
      biomechanical properties of the engineered tissue constructs were observed to
      increase with culture time reflecting the development of a tissuelike structure.
      These experimental findings suggest that viscoelastic material functions of the
      tissue constructs can provide valuable inputs for the stages of in vitro tissue
      development.

PMID- 20815649
TI  - The contribution of the perichondrium to the structural mechanical behavior of
      the costal-cartilage.
AB  - The costal-cartilage in the human ribcage is a composite structure consisting of
      a cartilage substance surrounded by a fibrous, tendon-like perichondrium. Current
      computational models of the human ribcage represent the costal-cartilage as a
      homogeneous material, with no consideration for the mechanical contributions of
      the perichondrium. This study sought to investigate the role of the perichondrium
      in the structural mechanical behavior of the costal-cartilage. Twenty-two
      specimens of postmortem human costal-cartilage were subjected to cantilevered
      like loading both with the perichondrium intact and with the perichondrium
      removed. The test method was chosen to approximate the cartilage loading that
      occurs when a concentrated, posteriorly directed load is applied to the
      midsternum. The removal of the perichondrium resulted in a statistically
      significant (two-tailed Student's t-test, p< or =0.05) decrease of approximately
      47% (95% C.I. of 35-58%) in the peak anterior-posterior reaction forces generated
      during the tests. When tested with the perichondrium removed, the specimens also
      exhibited failure in the cartilage substance in the regions that experienced
      tension from bending. These results suggest that the perichondrium does
      contribute significantly to the stiffness and strength of the costal-cartilage
      structure under this type loading, and should be accounted for in computational
      models of the thorax and ribcage.

PMID- 20815648
TI  - Fiber optic microneedles for transdermal light delivery: ex vivo porcine skin
      penetration experiments.
AB  - Shallow light penetration in tissue has been a technical barrier to the
      development of light-based methods for in vivo diagnosis and treatment of
      epithelial carcinomas. This problem can potentially be solved by utilizing
      minimally invasive probes to deliver light directly to target areas. To develop
      this solution, fiber optic microneedles capable of delivering light for either
      imaging or therapy were manufactured by tapering step-index silica-based optical
      fibers employing a melt-drawing process. Some of the microneedles were
      manufactured to have sharper tips by changing the heat source during the melt
      drawing process. All of the microneedles were individually inserted into ex vivo
      pig skin samples to demonstrate the feasibility of their application in human
      tissues. The force on each microneedle was measured during insertion in order to
      determine the effects of sharper tips on the peak force and the steadiness of the
      increase in force. Skin penetration experiments showed that sharp fiber optic
      microneedles that are 3 mm long penetrate through 2 mm of ex vivo pig skin
      specimens. These sharp microneedles had a minimum average diameter of 73 mum and
      a maximum tip diameter of 8 mum. Flat microneedles, which had larger tip
      diameters, required a minimum average diameter of 125 mum in order to penetrate
      through pig skin samples. Force versus displacement plots showed that a sharp tip
      on a fiber optic microneedle decreased the skin's resistance during insertion.
      Also, the force acting on a sharp microneedle increased more steadily compared
      with a microneedle with a flat tip. However, many of the sharp microneedles
      sustained damage during skin penetration. Two designs that did not accrue damage
      were identified and will provide a basis of more robust microneedles. Developing
      resilient microneedles with smaller diameters will lead to transformative, novel
      modes of transdermal imaging and treatment that are less invasive and less
      painful for the patient.

PMID- 20815650
TI  - In situ microindentation for determining local subchondral bone compressive
      modulus.
AB  - Alterations to joint tissues, including subchondral bone, occur with
      osteoarthritis. A microindentation technique was developed to determine the local
      compressive modulus of subchondral bone. This test, in conjunction with a
      cartilage indentation test at the same location, could evaluate changes of these
      material properties in both tissues. The accuracy of the technique was determined
      by applying it to materials of known moduli. The technique was then applied to
      rat tibial plateaus to characterize the local moduli of the subchondral bone. An
      established nanoindentation method was adopted to determine the modulus of
      subchondral bone following penetration of the overlying articular cartilage.
      Three cycles of repeated loadings were applied (2.452 N, 30 s hold). The slope of
      the load-displacement response during the unloading portion of the third cycle
      was used to measure the stiffness. Indentation tests were performed on two
      polyurethane foams and polymethyl-methacrylate for validation (n=15). Regression
      analysis was used to compare the moduli with reference values. Subchondral bone
      moduli of tibial plateaus from Sprague-Dawley rats (n=5) were measured for
      central and posterior locations of medial and lateral compartments. An analysis
      of variance was used to analyze the effects of compartment and test location. The
      measured moduli of the validation materials correlated with the reference values
      (R(2)=0.993, p=0.05). In rat tibial plateaus, the modulus of the posterior
      location was significantly greater than the center location (4.03+/-1.00 GPa and
      3.35+/-1.16 GPa respectively, p=0.03). The medial compartment was not different
      from the lateral compartment. This method for measuring the subchondral bone in
      the same location as articular cartilage allows studies of the changes in these
      material properties with the onset and progression of osteoarthritis.

PMID- 20815651
TI  - Design of a free-floating polycarbonate-urethane meniscal implant using finite
      element modeling and experimental validation.
AB  - The development of a synthetic meniscal implant that does not require surgical
      attachment but still provides the biomechanical function necessary for joint
      preservation would have important advantages. We present a computational
      experimental approach for the design optimization of a free-floating
      polycarbonate-urethane (PCU) meniscal implant. Validated 3D finite element (FE)
      models of the knee and PCU-based implant were analyzed under physiological loads.
      The model was validated by comparing calculated pressures, determined from FE
      analysis to tibial plateau contact pressures measured in a cadaveric knee in
      vitro. Several models of the implant, some including embedded reinforcement
      fibers, were tested. An optimal implant configuration was then selected based on
      the ability to restore pressure distribution in the knee, manufacturability, and
      long-term safety. The optimal implant design entailed a PCU meniscus embedded
      with circumferential reinforcement made of polyethylene fibers. This selected
      design can be manufactured in various sizes, without risking its integrity under
      joint loads. Importantly, it produces an optimal pressure distribution, similar
      in shape and values to that of natural meniscus. We have shown that a fiber
      reinforced, free-floating PCU meniscal implant can redistribute joint loads in a
      similar pattern to natural meniscus, without risking the integrity of the implant
      materials.

PMID- 20815652
TI  - Writing it down: an introduction.

PMID- 20815653
TI  - Community engagement: a key to successful rural clinical education.
AB  - Evaluation of rural clinical attachments has demonstrated that the rural setting
      provides a high-quality clinical learning environment that is of potential value
      to all medical students. Specifically, rural clinical education provides more
      'hands on' experience for students in which they are exposed to a wide range of
      common health problems and develop a high level of clinical competence. Northern
      Ontario in Canada is a large rural region that has a chronic shortage of
      healthcare providers. The Northern Ontario School of Medicine (NOSM) was
      established with a social accountability mandate to contribute to improving the
      health of the people and communities of Northern Ontario, and is a joint
      initiative of Laurentian University, Sudbury, and Lakehead University, Thunder
      Bay, which are over 1000 km apart. The NOSM has developed a distinctive model of
      medical education known as distributed community engaged learning (DCEL), which
      weaves together various recent trends in medical education including case-based
      learning, community-based medical education, electronic distance education and
      rural-based medical education (including the preceptor model). The NOSM
      curriculum is grounded in Northern Ontario and relies heavily on electronic
      communications to support DCEL. In the classroom and in clinical settings,
      students explore cases from the perspective of doctors in Northern Ontario. In
      addition, DCEL involves community engagement through which communities actively
      participate in hosting students and contribute to their learning.This paper
      explores the conceptual and practical issues of community engagement, with
      specific focus on successful rural clinical education. Community engagement takes
      the notion of 'community' in health sciences education beyond being simply
      community based in that the community actively contributes to hosting the
      students and enhancing their learning experiences. This is consistent with the
      focus on social accountability in medical education. Implementing community
      engagement is quite challenging; however; its potential benefits are substantial
      and include the improved recruitment and retention of healthcare providers who
      are responsive to cultural diversity and community needs and are collaborating
      members of the whole health team.

PMID- 20815654
TI  - Building capacity for acute care in developing countries.
AB  - The article provides a 'short journey' to neighbours in the Australasian region
      to highlight some innovation in health policy, rural health education, and
      professional teams, in developing countries. The innovations are described and
      challenges discussed.

PMID- 20815655
TI  - Referral patterns of patients presenting with chest pain at two rural emergency
      departments in Western Australia.
AB  - INTRODUCTION: Coronary heart disease is the largest single cause of death in
      Australia. In Western Australia invasive diagnostics and therapies for acute
      coronary syndromes are only provided in the metropolitan hospitals of Perth.
      Patients in rural hospitals who need invasive cardiac care have to be transferred
      to Perth. The aim of our research was to determine which patient factors are
      associated with referral to advanced cardiac care at metropolitan level and how
      this compares to Australian guidelines for the management of acute coronary
      syndromes. METHOD: Data was collected from patients presenting with chest pain to
      the rural emergency department, who were at least 18 years old and had given
      their consent. Exclusion criteria were chest pain accompanied or precipitated by
      significant co morbidity and prior enrolment in this study protocol.
      Socioeconomic and medical information of patients was collected from their
      medical records. Data was analysed using chi(2) tests, independent sample t-tests
      and multivariable logistic-regression models (stepwise backwards procedure).
      RESULTS: The study included 115 rural patients with chest pain with a mean age of
      58 years: 66 (57%) men, 12 (10%) indigenous Australians and 38 (33%) transferred
      patients. Of all transferred patients 19 (50%) had a positive peak troponin-T, 13
      (36%) a high peak creatine kinase (CK) and 12 (32%) persistent ST-elevation on
      their electrocardiogram, compared with 10 (14%), 12 (17%) and 11 (14%)
      respectively for non-transferred patients. Chi-square-tests showed significant
      differences between transfer groups in all three essential initial cardiac
      investigations and known dyslipidaemia. In multivariate analyses the positive
      peak troponin-T increased odds of transfer (OR6.40; 95% CI 2.55-16.08). This
      effect increased after adjustment for gender, serum creatinine and known
      dyslipidaemia (OR27.61; 95% CI 6.41-119.04). When adjusted for the peak troponin
      T, neither ECG with persistent ST-elevation nor high peak CK remained
      significant. Known dyslipidaemia remained significant and serum creatinine became
      significant. Gender became significant when adjusted for troponin-T, known
      dyslipidaemia and serum creatinine. CONCLUSIONS: Peak troponin-T is an
      independent determinant associated with the transfer to advanced care at
      metropolitan level, but ECG with persistent ST-elevation and peak CK (other
      essential initial cardiac investigations) are not. Further investigation of the
      available and provided cardiac care in rural Western Australia is required.

PMID- 20815656
TI  - How safe is GP obstetrics? An assessment of antenatal risk factors and perinatal
      outcomes in one rural practice.
AB  - INTRODUCTION: Approximately one-fifth of Western Australian women deliver their
      babies in rural and remote regions of the state. The medical workforce caring for
      these women is predominantly non-specialist GP obstetricians. This article
      explores how safe is rural GP obstetrics. It reviews one rural obstetric practice
      in detail. In particular it asks these questions: What are the antenatal risk
      factors? What are the obstetric outcomes for the mother? What are the obstetric
      outcomes for the baby? METHODS: This study is an audit of the author's obstetric
      practice over a two-year period from July 2007 to June 2009. The audit criteria
      included all obstetric patients managed by the author through to delivery and
      immediate post-partum care. Hospital and practice notes for 195 singleton
      pregnancies were reviewed. Antenatal risk factors, intrapartum events and
      immediate post-partum events for all patients cared for by the author through to
      delivery were recorded and compared with averages for Western Australia from
      published 2007 figures. RESULTS: The maternal population had mean age of 28.5
      years, 2.1% were Aboriginal. Body mass index (BMI) at booking was a mean of 27.1
      (range 18-40). Those with a BMI > 40 were referred elsewhere. Significant
      antenatal risks included smoking (14.9%), previous caesarean section (14.4%),
      hypertension (13.3%), pre-eclampsia (5.1%) and gestational diabetes (8.2%).
      Intrapartum there were high rates of induction (33.5%), epidural/spinal (34.7%)
      and shoulder dystocia (3.6%). Type of delivery was predominantly spontaneous
      vaginal (65.6%), vacuum (14.9%), forceps (2.6%), elective caesarean (9.7%) and
      non-elective caesarean (8.7%). Post-partum events included post-partum
      haemorrhage (10.3%), transfusion (1.5%), retained placenta (2.1%), neonatal
      jaundice (21.1%), neonatal seizures (1.5%) neonatal sepsis (1.5%) and neonatal
      special care or intensive care (SCU/NICU) admission (9.8%). CONCLUSIONS: The
      audit population was a group of relatively low risk pregnant women. Despite
      referral of more complicated patients to specialist services either in Kalgoorlie
      or to Perth, there remained a significant number of women who developed antenatal
      risk factors. There was a high rate of induction of labour, which reflected the
      high rates of hypertension and diabetes, both relative indicators for induction
      at term. There was a reassuringly high rate of spontaneous vaginal delivery and
      low rates of elective and non-elective caesarian section. Post-partum clinically
      significant events still occurred for mother and baby, although not at rates
      higher than expected elsewhere. The results of this audit show that in a rural
      setting where options for referral may be less than in an urban setting, it is
      still possible to practice obstetrics safely. These results support the
      hypothesis that it is safe to practice GP obstetrics particularly in a rural
      setting. An unexpected result in this audit was the high rate of gestational
      diabetes, which is significantly greater than the average published for Western
      Australia. Further investigation of rates of gestational diabetes in other rural
      populations is warranted to explore this further.

PMID- 20815657
TI  - Surfactant protein D modulates pulmonary clearance of pollen starch granules.
AB  - Pollen starch granules (PSGs) are allergen particles that get into contact with
      pulmonary surfactant and phagocytes in the terminal airways. In this study, the
      effects of surfactant protein D (SP-D) on the interaction of PSGs with phagocytes
      and on the pulmonary clearance of PSGs were determined. Fluorescently labeled
      PSGs were incubated in vitro with murine lung macrophages or dendritic cells
      (DCs) +/- recombinant rat SP-D (rrSP-D). In addition, the effect of SP-D on
      uptake of PSGs by lung macrophages and DCs was studied in vivo. Furthermore, PSGs
      were instilled in Balb/c mice and the effects of SP-D on total lung clearance
      were assessed by optical imaging. SP-D treatment increased the number of PSG
      positive macrophages and DCs in vitro. Furthermore, SP-D accelerated
      uptake/binding by alveolar macrophages and reduced the number of PSG-positive
      tissue macrophages and DCs at 24 hours. However, SP-D did not affect total lung
      clearance of PSGs and it did not enhance the T-cell proliferation induced by PSG
      positive DCs. In conclusion, SP-D increased PSG-positive cells in vitro and
      accelerated PSG binding/uptake in vivo. The observed effects were limited to
      cellular clearance mechanisms and did not affect the total clearance of PSGs from
      the lung.

PMID- 20815658
TI  - Characterization of peptide fragments from lung elastin degradation in chronic
      obstructive pulmonary disease.
AB  - This study presents a method for detecting and characterizing peptides of elastin
      that result from lung matrix injury in chronic obstructive pulmonary disease
      (COPD). Lung elastin degradation was studied by two representative in vivo
      elastases, human neutrophil elastase (HNE) and macrophage metalloproteinase
      (MMP12). The resulting peptide mixtures were analyzed by high-performance liquid
      chromatography/electrospray tandem mass spectrometry (LC/MSMS) to characterize 40
      elastin-derived peptides (EDPs), 24 from HNE and 16 from MMP12 digestions. The
      peptides constitute major EDPs that are solubilized by the enzymatic digestion.
      Using the selected reaction monitoring (SRM) from LC/MSMS analysis, the
      transition ions of the peptides were used to investigate the presence of the
      peptides in selected body fluids of chronic obstructive pulmonary disease (COPD)
      patients. Four peptides, GYPI, APGVGV, GLGAFPA, and VGVLPGVPT, were detected in
      plasma or sputum of some COPD patients but not in normal controls. A hexapeptide
      VGVAPG, which had been widely studied for its chemotactic activity for a possible
      pathogenic role in COPD, was not detected in lung EDPs by HNE or MMP12 digestion,
      but only by porcine pancreatic elastase (PPE) digestion. This study demonstrates
      a practical methodology to study peptides from matrix degradations in pulmonary
      disease and a means of investigating their pathogenesis.

PMID- 20815660
TI  - A clinical and health economic review of a prefilled insulin pen.
AB  - OBJECTIVE: Several different durable or disposable insulin pen delivery devices
      are currently available, and newer, improved devices are being introduced. One
      prefilled insulin device, FlexPen (FP), has recently been improved (known as the
      Next Generation FlexPen (NGFP) in Europe or the improved FlexPen in the United
      States). The aim of this review is to summarize the clinical and health economic
      data of FP and its modified version. METHODS: Relevant clinical and health
      economic terms relating to insulin pens were used to search Medline for studies
      and other publications involving FP and NGFP. RESULTS: Sixteen publications
      investigating FP and/or the NGFP were identified. Patients prefer FP and are more
      confident with its use in comparison to vial/syringe insulin administration: in a
      study of 105 patients with type 1 or type 2 diabetes, 85% of patients found FP to
      be more discreet for use in public than a syringe, 74% of patients found FP to be
      easier to use overall and 82% of patients had more confidence with setting the
      correct dose with FP. Four publications investigated the dosing accuracy of FP or
      NGFP: all studies found the study doses for both were within ISO-specified
      limits. Pharmacoeconomic issues with insulin pen devices were identified in four
      papers, and switching to FP from vial/syringe was found to increase treatment
      adherence from 59% to 68% (p < 0.01), as measured by medication possession ratio.
      Switching to FP is also a cost-effective option for patients. Mean all-cause
      annual treatment (-$1748/patient, p < 0.01), hypoglycaemia-attributable costs (
      $908/patient, p < 0.01), and other diabetes-attributable costs (-$643/patient, p
      < 0.01) were reduced following the switch from vial/syringe. CONCLUSIONS: Some
      limitations of traditional insulin administration devices can be overcome with
      insulin pen devices. FP is a prefilled disposable pen that has been modified to
      further improve characteristics beneficial to patient insulin administration.

PMID- 20815659
TI  - Regulation of cytokine-induced prostanoid and nitric oxide synthesis by
      extracellular signal&#x2013;regulated kinase 1/2 in lung epithelial cells.
AB  - The inflammatory cytokines tumor necrosis factor alpha (TNFalpha) and interferon
      gamma (IFNgamma) stimulate production of the inflammatory mediators prostaglandin
      E2 (PGEgamma), prostacyclin (PGIgamma), and nitric oxide (NO) in cultured lung
      epithelial cells. Pretreatment of these cells with the selective MEK1/2 (mitogen
      activated protein kinase/extracellular signal-regulated kinase [ERK] kinase 1/2)
      inhibitor U0126 blocked ERK1/2 activation and inhibited cytokine-induced
      production of these inflammatory mediators. Primary bronchiolar epithelial Clara
      cells treated with TNFalpha and IFNgamma also produced increased PGE2, PGI2, and
      NO, and PG and NO production was decreased by MEK inhibition. U0126
      differentially affected cyclooxygenase (COX)-1, COX-2, and inducible NO synthase
      (iNOS) expression in cell lines, however, suggesting that MEK1/2 regulates
      prostanoid and NO production by means other than inducing their biosynthetic
      enzymes. Functionally, inhibition of MEK1/2 caused G1 cell cycle arrest and
      decreased cyclin D1 expression, but these effects were not related to decreased
      prostanoid production. These results indicate separate proinflammatory and
      proliferative roles for ERK1/2 in lung epithelial cells. During lung tumor
      formation in vivo, ERK1/2 phosphorylation increased as lung tumors progressed.
      Since tumor-derived cells were more sensitive than nontumorigenic cells to the
      antiproliferative effects of U0126, MEK1/2 inhibition may serve as an attractive
      chemotherapeutic target.

PMID- 20815661
TI  - Adherence to controller therapy for chronic obstructive pulmonary disease: a
      review.
AB  - OBJECTIVE: While several studies have examined adherence to controller
      medications for the treatment of COPD, few systematic reviews have taken the
      translational step to identifying important and necessary areas for further
      research. The objective of this study was to review data on the outcomes of
      adherence to various controller therapies in patients with COPD in an effort to
      help prescribers understand adherence properties for each therapy. RESEARCH
      DESIGN AND METHODS: This is a systematic review of studies investigating
      adherence to an array of controller pharmaceutical regimens. The studies were
      obtained from PubMed during 2008 and 2009 using the following key words: chronic
      obstructive pulmonary disease, COPD, adherence, controller medication, and
      persistence. Only articles encompassing adherence or persistence data to
      controller medications and published after 1990 were utilized. RESULTS: After the
      search results were filtered for only the articles that pertained to adherence or
      persistence measurements in COPD, 35 articles remained; and finally, discounting
      those articles not published in English, articles which did not compare
      treatments for COPD, as well as those which were review articles, ten applicable
      articles remained. Each of these found low levels of medication adherence and/or
      persistence among patients receiving medications for COPD. Patients receiving
      fluticasone/salmeterol (FSC) and tiotropium (TIO) for treatment showed the
      highest adherence among all controller medications. Patients who were married,
      older, and white were more likely to adhere to their medications. CONCLUSION:
      Characteristics of the medication used (i.e. dosing schedule, formulation, etc.)
      as well as patient characteristics affect the adherence/persistence to
      medications for the treatment of COPD. Further patient education is necessary in
      order to effectively improve disease management and patient outcomes in COPD.
      There is a need for future research and educational efforts to improve adherence
      in COPD and more clearly identify specific behavioral and treatment
      characteristics associated with specific COPD medications that can facilitate
      adherence.

PMID- 20815662
TI  - How to reduce alcohol-related problems in adolescents: what can parents do and
      what can the government do?

PMID- 20815663
TI  - Parenting factors associated with reduced adolescent alcohol use: a systematic
      review of longitudinal studies.
AB  - OBJECTIVE: To identify parenting strategies associated with adolescent alcohol
      consumption that parents can use to implement new national guidelines regarding
      alcohol consumption by people under the age of 18. METHODS: A systematic search
      of academic literature employing the PRISMA method identified 77 relevant
      articles. Inclusion criteria for the review were (i) longitudinal cohort studies;
      (ii) measurement of one or more parenting factors during adolescence or pre
      adolescence (between the ages of 8 and 17) as a predictor (iii) outcome
      measurement of any alcohol use and/or alcohol related problems during adolescence
      at least one time point after the initial parenting factor was measured, and/or
      problem drinking in adulthood. Studies were excluded if alcohol use was combined
      with other substance use or problem behaviour as an outcome variable, or if
      different parenting factors were combined as a single predictor variable for
      analysis. Stouffer's method of combining p values was used to determine whether
      associations between variables were reliable. RESULTS: Twelve parenting variables
      were investigated in these studies: parental modelling, provision of alcohol,
      alcohol-specific communication, disapproval of adolescent drinking, general
      discipline, rules about alcohol, parental monitoring, parent-child relationship
      quality, family conflict, parental support, parental involvement, and general
      communication. We found that delayed alcohol initiation was predicted by:
      parental modelling, limiting availability of alcohol to the child, parental
      monitoring, parent-child relationship quality, parental involvement and general
      communication. Reduced levels of later drinking by adolescents were predicted by:
      parental modelling, limiting availability of alcohol to the child, disapproval of
      adolescent drinking, general discipline, parental monitoring, parent-child
      relationship quality, parental support and general communication. CONCLUSIONS: A
      number of parenting strategies were identified that parents can use to reduce
      their adolescent's alcohol consumption. These could be promoted to parents to
      help them implement new national guidelines on alcohol use.

PMID- 20815664
TI  - The effect of the draft DSM-5 criteria for GAD on prevalence and severity.
AB  - OBJECTIVE: Options for revising the DSM-IV Generalized Anxiety Disorder (GAD)
      diagnostic criteria have been made by the DSM-5 Anxiety, Obsessive-Compulsive,
      Post-traumatic and Dissociative Disorders Work Group. It has been proposed that
      renaming the disorder Generalized Worry Disorder, clarifying criterion A to
      emphasize the primacy of worry, reducing the duration required, altering the list
      of associated symptoms to reflect the concomitants of worry that are specific to
      GAD, and adding behavioural criteria could clarify the concept of chronic worry
      for clinicians and enhance the reliability of the diagnosis. The influence of the
      proposed changes on the prevalence and severity of cases is examined. METHOD:
      Data from a national survey and from a clinical data set were used to quantify
      the effect of the proposed changes. RESULTS: Reducing the duration from 6 to 3
      months and removing the clinical significance criterion raised the prevalence of
      GAD, whereas revising the associated symptoms and adding behavioural symptoms
      reduced the prevalence. With all the new options implemented, although the
      prevalence of the diagnosis rose by 9%, it was associated with similar levels of
      distress and impairment as DSM-IV cases. CONCLUSIONS: There is preliminary
      evidence that the proposals may increase the prevalence of GAD but may not
      influence the severity of cases. The clinical utility, reliability and validity
      of the diagnosis remains to be established.

PMID- 20815665
TI  - Psychometric validation of the Growth and Empowerment Measure (GEM) applied with
      Indigenous Australians.
AB  - OBJECTIVE: Empowerment is a complex process of psychological, social,
      organizational and structural change. It allows individuals and groups to achieve
      positive growth and effectively address the social and psychological impacts of
      historical oppression, marginalization and disadvantage. The Growth and
      Empowerment Measure (GEM) was developed to measure change in dimensions of
      empowerment as defined and described by Aboriginal Australians who participated
      in the Family Well Being programme. METHOD: The GEM has two components: a 14-item
      Emotional Empowerment Scale (EES14) and 12 Scenarios (12S). It is accompanied by
      the Kessler 6 Psychological Distress Scale (K6), supplemented by two questions
      assessing frequency of happy and angry feelings. For validation, the measure was
      applied with 184 Indigenous Australian participants involved in personal and/or
      organizational social health activities. RESULTS: Psychometric analyses of the
      new instruments support their validity and reliability and indicate two-component
      structures for both the EES (Self-capacity; Inner peace) and the 12S (Healing and
      enabling growth, Connection and purpose). Strong correlations were observed
      across the scales and subscales. Participants who scored higher on the newly
      developed scales showed lower distress on the K6, particularly when the two
      additional questions were included. However, exploratory factor analyses
      demonstrated that GEM subscales are separable from the Kessler distress measure.
      CONCLUSION: The GEM shows promise in enabling measurement and enhancing
      understanding of both process and outcome of psychological and social empowerment
      within an Australian Indigenous context.

PMID- 20815666
TI  - Neurological soft signs in individuals with schizotypal personality features.
AB  - OBJECTIVE: The current study attempted to examine the prevalence of neurological
      soft signs and their relationships with schizotypal traits in individuals with
      psychometrically defined schizotypal personality disorder (SPD) features. METHOD:
      Sixty-four individuals with SPD-proneness and 51 without SPD-proneness were
      recruited for the present study. The soft signs subscales of the Cambridge
      Neurological Inventory were administered to all participants; the Schizotypal
      Personality Questionnaire (SPQ) was administered to SPD-proneness and non-SPD
      proneness participants. RESULTS: The SPD-proneness participants demonstrated
      significantly higher prevalence of soft signs than those without SPD-proneness.
      SPQ subscales were significantly associated with ratings of motor coordination,
      sensory integration and total soft signs. CONCLUSION: These findings suggest that
      neurological soft signs are trait markers of schizophrenia.

PMID- 20815667
TI  - Smoking status, mental disorders and emotional and behavioural problems in young
      people: child and adolescent component of the National Survey of Mental Health
      and Wellbeing.
AB  - OBJECTIVE: To examine the relationship between smoking behaviour, mental
      disorders and emotional and behavioural problems in a nationally representative
      sample of young people. METHOD: Data were taken from the child and adolescent
      component of the National Survey of Mental Health and Wellbeing which assessed
      mental health problems in two main ways: using a fully structured interview (the
      Diagnostic Interview Schedule for Children) and using the Child Behaviour
      Checklist and the Youth Self Report, which assess emotional and behavioural
      problems on a dimensional scale. The relationship between smoking and mental
      health problems was assessed using logistic regression. RESULTS: Among young
      people with conduct disorder 72% had smoked in the last 30 days, 46% of young
      people with depressive disorder, and 38% among young people with attention
      deficit hyperactivity disorder. This compared with 21% of young people with none
      of these disorders. Odds ratios (OR) for current smoking were consistently
      elevated for young people with mental health problems after adjusting for
      demographic and socio-economic factors across all measures of mental health used.
      The OR for current smoking in young people with parent-reported externalizing
      behaviours in the clinical range was 4.5 (95%CI: 3.1-6.8), and for young people
      with parent-reported internalizing problems in the clinical range the OR was 2.7
      (95%CI: 1.8-4.0). Young people with mental health problems started smoking on
      average at a younger age, were more likely to progress to current smoking, and
      smoked on average a higher number of cigarettes per day. CONCLUSIONS: After
      adjusting for demographic and socio-economic factors, young people with mental
      health problems were more likely to start smoking, progress to daily smoking, and
      smoke more heavily. Mental illness is an important issue to consider in tobacco
      control in young people.

PMID- 20815668
TI  - Accuracy of official suicide mortality data in Queensland.
AB  - OBJECTIVE: The purpose is to answer the following research question: are the time
      series data published by the Australian Bureau of Statistics for Queensland
      statistically the same as those of the Queensland Suicide Register? METHOD: This
      question was answered by first modelling statistically, for males and females,
      the time series suicide data from these two sources for the period of data
      availability, 1994 to 2007 (14 observations). Fitted values were then derived
      from the 'best fit' equations, after rigorous diagnostic testing. The outliers in
      these data sets were addressed with pulse dummy variables. Finally, by applying
      the Wald test to determine whether or not the fitted values are the same, we
      determined whether, for males and females, these two data sets are the same or
      different. RESULTS: The study showed that the Queensland suicide rate, based on
      Queensland Suicide Register data, was greater than that based on Australian
      Bureau of Statistics data. Further statistical testing showed that the
      differences between the two data sets are statistically significant for 24 of the
      28 pair-wise comparisons. CONCLUSIONS: The quality of Australia's official
      suicide data is affected by various practices in data collection. This study
      provides a unique test of the accuracy of published suicide data by the
      Australian Bureau of Statistics. The Queensland Suicide Register's definition of
      suicide applies a more suicidological, or medical/health, conception of suicide,
      and applies different practices of coding suicide cases, timing of data
      collection processes, etc. The study shows that 'difference' between the two data
      sets predominates, and is statistically significant; thus the extent of the under
      reporting of suicide is not trivial. Given that official suicide data are used
      for many purposes, including policy evaluation of suicide prevention programmes,
      it is suggested that the system used in Queensland should be adopted by the rest
      of Australia too.

PMID- 20815669
TI  - Prevalence of self-management versus formal service use for common mental
      disorders in Australia: findings from the 2007 National Survey of Mental Health
      and Wellbeing.
AB  - OBJECTIVE: To determine the proportion of Australian adults who use non
      practitioner led support services and self-management strategies for common
      mental disorders. METHOD: Data were drawn from the 2007 National Survey of Mental
      Health and Wellbeing, a representative survey of 8841 Australian adults aged 16
      to 85 years. This survey included the Composite International Diagnostic
      Instrument to obtain diagnosis of International Classification of Diseases
      (Version 10; ICD-10) mental disorders. Information about consultations with
      health professionals for mental health problems and the use of support services
      and self-management strategies was also collected. RESULTS: Half of all adults
      who met the criteria for an affective or anxiety disorder in the last 12 months
      reported using non-practitioner led support services and/or self-management
      strategies for their mental health problems. Six per cent used support services,
      including Internet and non-online support groups and telephone counselling, and
      51.9% used self-management strategies such as doing 'more of the things you
      enjoy' to 'help deal with' their mental health problems. Of people with a 12
      month common mental disorder, 24% used support services and/or self-management
      strategies without additional formal services; 29.3% used both. Of adults with a
      12-month affective or anxiety disorder, 37% used neither formal services nor self
      management strategies. A substantial proportion of people who reported using self
      management strategies for their mental health did not have a diagnosable
      affective or anxiety disorder. CONCLUSIONS: The use of non-practitioner led
      support services and self-management strategies for mental health problems, with
      and without adjunct use of formal health services, is widespread in Australia.
      Future research is needed to investigate why people may select these strategies
      over formal services, or whether self-management reflects the presence of
      barriers to use of formal services.

PMID- 20815670
TI  - Do dispositional rumination and/or mindfulness moderate the relationship between
      life hassles and psychological dysfunction in adolescents?
AB  - OBJECTIVE: This study examined the moderating effects of dispositional rumination
      and mindfulness on the relationship between recent life hassles and adolescent
      mental health (operationalized as symptoms of depression, anxiety and stress).
      METHOD: Data collected from a sample of 317 Australian high school students
      comprised an inventory of recent life hassles, measures of dispositional
      rumination and dispositional mindfulness and an assessment of current symptoms of
      depression, anxiety and stress. RESULTS: An increased incidence of recent life
      hassles was reliably associated with increased depressive symptoms, anxiety and
      stress. However, moderation analyses revealed that dispositional rumination
      exacerbated the relationship between life hassles and symptoms of depression and
      anxiety, whereas dispositional mindfulness attenuated the relationship between
      life hassles and symptoms of depression, anxiety and stress. CONCLUSIONS:
      Interventions to increase dispositional mindfulness in childhood are proposed as
      a method of protecting the psychological well-being of adolescents confronted by
      inevitable everyday life stress.

PMID- 20815671
TI  - Development and psychometric evaluation of a measure to assess distress in
      partners of Australian combat veterans.
AB  - OBJECTIVE: The aim of the present study was to develop and evaluate a
      multidimensional measure of distress experienced by partners of Australian combat
      veterans. METHOD: The Partners of Veterans Distress Scale (POV-DS) was developed
      using factor analysis on a sample of 665 female members of Partners of Veterans
      Association of Australia. Content validity for the scale was established by using
      focus groups and expert feedback during item development phase. In addition, two
      self-report inventories were administered to assess physical/mental health, and
      satisfaction with life. RESULTS: Following principal-axis factoring, 45 items
      were retained, loading on seven distinct but correlated factors: Sleep problems,
      Hyper-vigilance, Social isolation, Financial problems, Intimacy problems,
      Exhaustion, and Negative affect. The factor structure was cross-validated using
      confirmatory factor analysis on a hold-out sample. The distress subscales all
      exhibited excellent internal consistency (alphas ranged from 0.84 to 0.95).
      Validation analyses revealed subscales derived from the seven-factor model
      explained 31% to 45% of the variance in partners' physical health, mental health,
      and satisfaction with life. CONCLUSIONS: The study found that the POV-DS is a
      reliable and valid tool for assessing distress in partners of Australian combat
      veterans.

PMID- 20815672
TI  - Mental health workers' views on addressing tobacco use.
AB  - OBJECTIVE: The aims of this study were to assess mental health workers' attitudes
      to addressing tobacco dependence with patients, to identify barriers that may
      prevent people with mental illness from receiving support, and determine workers'
      recommendations for tobacco policy and practice change. METHOD: Questionnaires
      were sent to government and non-government mental health services in Adelaide,
      South Australia. The questionnaires asked workers to rate on a Likert rating
      scale their attitudes to addressing tobacco use with patients and to respond to
      qualitative questions about managing tobacco use within mental health services.
      Quantitative data were analysed using SPSS version 15.0 and qualitative data was
      coded by three researchers into categories or themes and then analysed. RESULTS:
      Questionnaires (324) were received from staff across 45 organizations providing
      clinical and psychosocial services. More than two thirds of the participants felt
      it was important for mental health services to be involved in assisting patients
      to quit smoking; however, only 26% said they raised the issue of tobacco use with
      patients, often or as part of the assessment. Respondents on average felt
      approximately one third of their patients could quit or reduce tobacco use if
      they received nicotine replacement therapy, information and support. Most workers
      suggested changes to policy and practice within mental health services including
      smoke free areas and the provision of information and support. DISCUSSION: The
      rate of tobacco use amongst people with mental illness is still very high with
      serious social and health consequences. Mental health workers are uniquely placed
      to assist patients to quit or reduce tobacco use. This study has shown many
      workers believe that it is important to address tobacco use with their patients
      as part of routine care and that mental health services should implement
      significant tobacco policy and practice change.

PMID- 20815673
TI  - Association between abnormal psychosocial situations in childhood, generalized
      anxiety disorder and oppositional defiant disorder.
AB  - OBJECTIVE: Psychosocial stressors are important in the pathogenesis of most
      mental disorders. However, little is known about the way psychosocial stressors
      uniquely combine to create risk for different expressions of child and adolescent
      psychopathology. The purpose of this study was to determine whether core
      dimensions of stressful psychosocial situations are differentially associated
      with childhood generalized anxiety disorder and oppositional defiant disorder.
      METHOD: A case-control design conducted in Trondheim (Norway) from 2002 to 2004
      comparing exposure to ICD-10-defined abnormal psychosocial situations (Z-codes)
      among 21 children with oppositional defiant disorder (ODD) and 22 children with
      generalized anxiety disorder (GAD) recruited from a university outpatient clinic
      with 42 non-patient school controls. RESULTS: Multigroup discriminant analysis
      extracted two significant dimensions within the psychosocial variables assessed.
      Function 1 was characterized by overprotection, parental pressures and acute life
      events and was associated with GAD. Function 2 was characterized by parental
      abuse/hostility and interpersonal stress and was associated with ODD. Both
      dimensions were able to correctly classify 89.7% of the cases, compared to 35.9%
      by chance. CONCLUSIONS: The results indicate that specific psychosocial
      dimensions are differentially related to childhood GAD and ODD. This may be
      useful in targeting at-risk populations for preventive intervention as well as
      informing more accurate alignment of psychosocial resources for treatment.

PMID- 20815674
TI  - Shared obsessive-compulsive disorder: broadening the concept of shared psychotic
      disorder.
AB  - OBJECTIVE: Folie a deux (shared psychotic disorder) is often described in the
      context of schizophrenia. In this article we present this syndrome in a non
      psychotic context. METHOD: We report a case of induced obsessive-compulsive
      disorder (OCD) in a married couple. Six months after the deterioration in the
      patient's OCD, his wife developed the same symptoms with no preceding history of
      an Axis I disorder. Neither spouse demonstrated psychotic symptomatology. The
      husband was successfully treated on an outpatient basis with Citalopram and
      Clonazepam. His wife's OCD spontaneously resolved without medication in parallel
      with the resolution of her husband's OCD. RESULTS: We highlight the uncommon
      phenomenon of shared psychiatric disorder occurring in the context of OCD. In the
      current psychiatric diagnostic nomenclature, (DSM IV and ICD10), there is no
      category for a non-psychotic shared psychiatric disorder. We raise the question
      of broadening the concept of shared disorder so as to include shared OCD and
      perhaps other shared psychiatric syndromes. CONCLUSIONS: More controlled studies
      are required in order to better understand the psychopathology and mechanisms of
      psychotic and non-psychotic shared disorders in psychiatry. We believe there are
      important treatment implications of such an understanding.

PMID- 20815675
TI  - Delirium as a symptom of tricyclic antidepressant withdrawal.

PMID- 20815676
TI  - Neonatal growth outcomes and in utero exposure to antidepressants: biological or
      social?

PMID- 20815677
TI  - Indications for antidepressant medication use in Australian general practice
      patients.

PMID- 20815679
TI  - 11th Australasian Schizophrenia Conference, Sydney, Australia, 22-24 September
      2010. Abstracts.

PMID- 20815678
TI  - Aggression and restraint in child inpatient units.

PMID- 20815687
TI  - Abstracts of the 22nd International Conference of the Society for Medical
      Innovation and Technology (SMIT). September 2-4, 2010. Trondheim, Norway.

PMID- 20815688
TI  - The societal impact of pain in the European Union: health-related quality of life
      and healthcare resource utilization.
AB  - OBJECTIVES: This paper reports on the results of a series of quantitative
      assessments of the association of severe and frequent pain with health-related
      quality of life and healthcare resource utilization in five European countries.
      METHODS: The analysis contrasts the contribution of the increasing severity and
      frequency of pain reported against respondents reporting no pain in the previous
      month. The data are taken from the 2008 National Health and Wellness Survey.
      Single-equation generalized linear regression models are used to evaluate the
      association of pain with the physical and mental component scores of the SF-12
      questionnaire as well as health utilities generated from the SF-6D. In addition,
      the role of pain is assessed in its association with healthcare provider visits,
      emergency room visits and hospitalizations. RESULTS: The results indicate that
      the experience of pain, notably severe and frequent pain, is substantial and is
      significantly associated with the SF-12 physical component scores, health
      utilities and all aspects of healthcare resource utilization, which far outweighs
      the role of demographic and socioeconomic variables, health risk factors (in
      particular body mass index) and the presence of comorbidities. In the case of
      severe daily pain, the marginal contribution of the SF-12 physical component
      score is a deficit of -17.86 compared to those reporting no pain (population
      average score 46.49), while persons who are morbidly obese report a deficit of
      only -6.63 compared to those who are normal weight. The corresponding association
      with health utilities is equally dramatic with a severe daily pain deficit of 
      0.19 compared to those reporting no pain (average population utility 0.71).
      CONCLUSIONS: For the five largest EU countries, the societal burden of pain is
      considerable. The experience of pain far outweighs the contribution of more
      traditional explanations of HRQoL deficits as well as being the primary factor
      associated with increased provider visits, emergency room visits and
      hospitalizations.

PMID- 20815689
TI  - New pre-analytical approach for the deep proteome analysis of sera from
      pancreatitis and pancreas cancer patients.
AB  - The presence of high-abundance proteins and the wide dynamic range of protein
      distribution complicates the proteome analysis of crude serum. The aim was to
      establish a new preanalytical protocol for analysis of the deep serum-proteome
      for biomarker discovery. METHODS: We investigated the stability and functionality
      of ProteoMinerTM and tested the new protocol by SELDI-TOF-MS profiling with serum
      samples obtained from patients with different pancreatic diseases. RESULTS: We
      developed a high-throughput protocol and proved the convenience of ProteoMinerTM
      in the 96-well format to provide insights into the deep serum proteome and
      facilitate the detection of novel serum biomarkers. Serum samples spiked with
      defined amounts of insulin, processed with ProteoMinerTM and analyzed by SELDI
      TOF-MS revealed that the concentration of the spiked insulin was not altered by
      ProteoMinerTM treatment. CONCLUSION: ProteoMinerTM technology is robust
      preanalytical step and can be used in a high-throughput format for analysis of
      low-abundant proteins in serum.

PMID- 20815690
TI  - Interface pressure distribution of elderly Japanese people in the sitting
      position.
AB  - AIM: To investigate the characteristics of elderly Japanese people sitting in a
      wheelchair using pressure mapping and an objective method to classify sitting
      patterns. METHOD: This descriptive observational study was conducted in a senior
      care facility and a geriatric hospital, with 107 elderly subjects (37 group A
      (house-bound), 34 group B (chair-bound) and 36 group C (bed-bound)) and 36 able
      bodied. Maximum pressure, total support area, distance from backrest to coccyx
      and sitting pattern were collected by using a pressure mapping system. RESULTS:
      Maximum pressure was significantly lower for able-bodied than groups B and C (p <
      0.001 and p = 0.024, respectively). Total support area was significantly larger
      for able-bodied than each elderly group (group A p = 0.014, group B p = 0.021,
      and group C p < 0.001). Distance from backrest to coccyx was significantly longer
      for group C than able-bodied (p < 0.001). The occurrence of proper sitting
      pattern significantly decreased as the degree of independence reduced (p <
      0.001). CONCLUSION: Elderly people with disabilities have high interface pressure
      on a small support area, malposition, which is confirmed by longitudinal and
      lateral supporting balance indices, and imbalance in a wheelchair. The following
      concepts for developing cushions should be considered: low interface pressure
      with large support area, individual adjustment of sitting position and stability
      of body trunk.

PMID- 20815691
TI  - Looking ahead: planning for the first human intracortical visual prosthesis by
      using pilot data from focus groups of potential users.
AB  - In planning for our research team's first human implant of a technologically
      advanced intracortical visual prosthesis we have conducted three focus groups
      with blind persons from a pool of likely participants. Guided by the principles
      of the Independent Living movement and Participatory Action Research (PAR), we
      asked the participants to share their thoughts and concerns about the procedure.
      The preliminary results reveal that achievement of the desired highest ethical of
      informed consent will require extensive pre-operative learning opportunities,
      such as those provided by these focus groups. Persons who are blind may be
      motivated to participate in research like this based on a need to know,
      understand, and explore ones environment, to leave a legacy, and to experience
      some restored perception.

PMID- 20815692
TI  - Agreement between parents and clinicians for the motor functional classification
      systems of children with cerebral palsy.
AB  - PURPOSE: This study aimed to evaluate whether parental ratings of expanded and
      revised Gross Motor Function Classification System (GMFCS E&R) and Manual Ability
      Classification System (MACS) had agreement with clinicians' ratings when
      classifying children with CP to these two well-known classifications of motor
      functioning and hereby to evaluate intertester reliability of the classification
      systems between clinicians and parents. METHOD: The process of study was designed
      to collect data from parents using the GMFCS E&R and MACS. The total participants
      consisted of 100 children with CP and their parents. The overall agreement
      between the parents and physiotherapist GMFCS and MACS scores was analysed using
      intraclass correlation coefficient (ICC). RESULTS: The ICC value between parents
      and physiotherapist was 0.96 (95% confidence interval [CI] 0.95-0.97) for GMFCS
      and 0.96 (95% CI 0.94-0.97) for MACS and indicated excellent agreement.
      CONCLUSIONS: The excellent agreement between parents and clinicians indicated
      that parents and clinicians can talk in the same language for the motor
      functional classification systems of children with CP if careful administrations
      are provided.

PMID- 20815693
TI  - Essential oil from rhizomes of Ligusticum chuanxiong induces apoptosis in
      hypertrophic scar fibroblasts.
AB  - CONTEXT: Hypertrophic scarring following surgical procedures, trauma and
      especially burns can lead to severe functional and cosmetic impairment, causing a
      decrease in the quality of life. Although a wide choice of treatments is offered,
      few therapeutic methods are universally accepted because of their side effects.
      OBJECTIVE: The effects of the essential oil (EO) extracted from rhizomes of
      Ligusticum chuanxiong Hort. (Umbelliferae) in human hypertrophic scar fibroblasts
      (HSFs) are investigated for the first time. MATERIALS AND METHODS: Chemical
      composition of hydrodistilled EO obtained from rhizomes of Ligusticum chuanxiong
      was analyzed by gas chromatography-mass spectrometry (GC-MS). The effects of EO
      on cell viability, apoptosis rate, mitochondrial membrane potential (MMP),
      lactate dehydrogenase (LDH), reactive oxygen species (ROS) and caspase-3 in HSFs
      were investigated. RESULTS: The experimental results showed that EO significantly
      inhibited cell viability, elicited morphological changes and induced apoptosis in
      HSFs. EO also evidently increased the loss of MMP, the levels of LDH release and
      cellular ROS production, and the activity of caspase-3. DISCUSSION AND
      CONCLUSION: EO-induced apoptosis was at least partially carried out via
      destruction of the intracellular antioxidant system and elicitation of excessive
      ROS accumulation in HSFs, which impaired mitochondrial membranes and elicited
      caspase-3 activation. EO could be an effective cure for human hypertrophic scar.

PMID- 20815694
TI  - Venous thromboembolism: deep venous thrombosis and pulmonary embolism in a
      neurosurgical population.
AB  - OBJECT: Venous thromboembolism (VTE), a combination of deep venous thrombosis
      (DVT) and pulmonary embolism (PE), is a major cause of morbidity and death in
      neurosurgical patients. This study evaluates 1) the risk of developing lower
      extremity DVT following a neurosurgical procedure; 2) the timing of initiation of
      pharmacological DVT prophylaxis upon the occurrence of VTE; and 3) the
      relationship between DVT and PE as related to VTE prophylaxis in neurosurgical
      patients. METHODS: The records of all neurosurgical patients between January 2006
      and December 2008 (2638 total) were reviewed for clinical documentation of VTE.
      As part of a quality improvement initiative, a subgroup of 1638 patients was
      studied during the implementation of pharmacological prophylaxis. A high-risk
      group of 555 neurosurgical patients in the intensive care unit underwent
      surveillance venous lower-extremity duplex ultrasonography studies twice weekly.
      All patients throughout the review received mechanical DVT prophylaxis.
      Pharmacological DVT prophylaxis, consisting of 5000 U of subcutaneous heparin
      twice daily (initially started within 48 hours of a neurosurgical procedure and
      subsequently within 24 hours of a procedure) was implemented in combination with
      mechanical prophylaxis. The DVT and PE rates were calculated for each group.
      RESULTS: In the surveillance group (555 patients), 84% of the DVTs occurred
      within 1 week and 92% within 2 weeks of a neurosurgical procedure. There was a
      linear correlation between the duration of surgery and DVT development. The use
      of subcutaneous heparin reduced the rate of DVT from 16% to 9% when medication
      was given at either 24 or 48 hours postoperatively, without any increase in
      hemorrhagic complications. In the overall group (2638 patients), there were 94
      patients who exhibited clinical signs of a possible PE and therefore underwent
      spiral CT; 22 of these patients (0.8%) had radiological confirmation of PE. There
      was no correlation between the use of pharmacological prophylaxis at either time
      point and the occurrence of PE, despite a 43% reduction in the lower-extremity
      DVT rate with pharmacological intervention. CONCLUSIONS: The majority of DVTs
      occurred within the first week after a neurosurgical procedure. There was a
      linear correlation between the duration of surgery and DVT occurrence. Use of
      early subcutaneous heparin (at either 24 or 48 hours) was associated with a 43%
      reduction of developing a lower-extremity DVT, without an increase in surgical
      site hemorrhage. There was no association of pharmacological prophylaxis with
      overall PE occurrence.

PMID- 20815695
TI  - Prophylactic correction of the international normalized ratio in neurosurgery: a
      brief review of a brief literature.
AB  - Prophylactic fresh-frozen plasma (FFP) transfusion is often undertaken in
      hemodynamically stable patients with a minimally elevated international
      normalized ratio (INR) prior to invasive procedures, despite little evidence in
      support of this practice. The authors review the current literature in an attempt
      to clarify best clinical practice with regard to this issue. Although the
      activated partial thromboplastin time and prothrombin time-INR are useful
      laboratory tests to measure specific clotting factors in the coagulation cascade,
      in the absence of active bleeding or a preexisting coagulopathy, their utility as
      predictors of overall bleeding risk is limited. Several studies have shown an
      imperfect correlation between mild elevations in the INR and subsequent bleeding
      tendency. Furthermore, FFP transfusion is not always sufficient to achieve normal
      INR values in patients who have mild elevations (< 2) to begin with. Finally,
      there are risks associated with FFP transfusion, including potential transfusion
      associated [disease] exposures as well as the time delay imposed by laboratory
      testing and transfusion administration prior to initiation of procedures. The
      authors propose that the current concept of a "normal" INR value warrants
      redefinition to make it a more meaningful clinical tool. Based on their review of
      the literature, the authors suggest that in a hemodynamically stable patient
      population there is a range of mildly prolonged INR values for which FFP
      transfusion is not beneficial, and is potentially harmful.

PMID- 20815696
TI  - International normalized ratio.

PMID- 20815697
TI  - Transfusion.

PMID- 20815698
TI  - Defining the "edge of the envelope": patient selection in treating complex sellar
      based neoplasms via transsphenoidal versus open craniotomy.
AB  - OBJECT: Endonasal approaches have become the gold standard intervention for many
      anterior and middle skull base tumors. The authors aimed to define some of the
      existing limitations of these approaches by reviewing their experience with
      complex sellar region tumors that were initially considered for both
      transsphenoidal and open skull base approaches and were thus deemed tumors at
      "the edge of the envelope." METHODS: Between April 2008 and April 2010, 250
      transsphenoidal operations were performed at Brigham and Women's Hospital. All
      cases were retrospectively reviewed to identify patients with complex sellar
      region tumors that were initially considered for, or soon thereafter required, an
      open craniotomy as the definitive treatment. The anatomical tumor characteristics
      that posed limitations to performing safe and effective endonasal skull base
      operations were reviewed. RESULTS: Thirteen cases exemplifying some of the
      existing limitations to achieving optimal surgical outcomes via transsphenoidal
      based approaches are presented. The following 8 factors are separately discussed
      that repeatedly limited the extent of resection, increased the risk of the
      operation, and contributed to perioperative complications: significant
      suprasellar extension, lateral extension, retrosellar extension, brain invasion
      with edema, firm tumor consistency, involvement or vasospasm of the arteries of
      the circle of Willis, and encasement of the optic apparatus or invasion of the
      optic foramina. CONCLUSIONS: Although the ability to approach and resect complex
      tumors using endonasal skull base techniques has evolved dramatically in recent
      years, several inherent tumor characteristics mandate extensive preoperative
      consideration. In selected cases these characteristics may lend support to
      selecting an open craniotomy as the initial operation.

PMID- 20815699
TI  - Coagulation factor levels in neurosurgical patients with mild prolongation of
      prothrombin time: effect on plasma transfusion therapy.
AB  - OBJECT: Neurosurgical patients often have mildly prolonged prothrombin time (PT)
      or international normalized ratio (INR). In the absence of liver disease this
      mild prolongation appears to be due to the use of very sensitive PT reagents.
      Therefore, the authors performed relevant coagulation factor assays to assess
      coagulopathy in such patients. They also compared plasma transfusion practices in
      their hospital before and after the study. METHODS: The authors tested 30 plasma
      specimens from 25 patients with an INR of 1.3-1.7 for coagulation factors II,
      VII, and VIII. They also evaluated plasma orders during the 5-month study period
      and compared them with similar poststudy periods following changes in plasma
      transfusion guidelines based on the study results. RESULTS: At the time of plasma
      orders the median INR was 1.35 (range 1.3-1.7, normal reference range 0.9-1.2)
      with a corresponding median PT of 13.6 seconds (range 12.8-17.6 seconds). All
      partial thromboplastin times were normal (median 29.0 seconds, range 19.3-33.7
      seconds). The median factor VII level was 57% (range 25%-124%), whereas the
      hemostatic levels recommended for major surgery are 15%-25%. Factors II and VIII
      levels were also within the hemostatic range (median 72% and 118%, respectively).
      Based on these scientific data, plasma transfusion guidelines were modified and
      resulted in a 75%-85% reduction in plasma orders for mildly prolonged INR over
      the next 2 years. CONCLUSIONS: Neurosurgical patients with a mild prolongation of
      INR (up to 1.7) have hemostatically normal levels of important coagulation
      factors, and the authors recommend that plasma not be transfused to simply
      correct this abnormal laboratory value.

PMID- 20815700
TI  - Antioxidant and drug detoxification potential of aqueous extract of Annona
      senegalensis leaves in carbon tetrachloride-induced hepatocellular damage.
AB  - CONTEXT:  Despite the myriad uses of Annona senegalensis Pers. (Annonaceae)
      leaves in folklore medicine of Nigeria, the basis is yet to be substantiated by
      scientific investigations. OBJECTIVES:  To investigate the antioxidant (in vitro
      and in vivo) and drug detoxification potential of aqueous extract of A.
      senegalensis leaves in CCl4-induced hepatocellular damage. MATERIALS AND METHODS:
      In vitro antioxidant activity of the aqueous extract of A. senegalensis leaves
      was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), H2O2, superoxide ion,
      2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate) (ABTS) and ferric ion models
      while in vivo antioxidant and drug detoxification activities of the extract at
      100, 200, and 400 mg/kg body weight were done by assaying the levels of enzymic
      and non-enzymic indices in CCl4-induced hepatocellular damage. RESULTS:  The
      extract at 1 mg/mL scavenged DPPH, H2O2, superoxide ion, and ABTS radicals,
      whereas ferric ion was significantly (P <0.05) reduced. The levels of alkaline
      and acid phosphatases, alanine and aspartate aminotransferases, superoxide
      dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6
      phosphate dehydrogenase, reduced glutathione, vitamins C and E, glutathione S
      transferase, nicotinamide adenine dinucleotide (reduced):Quinone oxidoreductase,
      uridyl diphosphoglucuronyl transferase, malondialdehyde, and lipid hydroperoxide
      that decreased in CCl4 treated animals were significantly attenuated by the
      extract in a manner similar to the animals treated with the reference drug.
      DISCUSSION AND CONCLUSION:  The ability of the aqueous extract of A. senegalensis
      leaves to scavenge free radicals in vitro and reversal of CCl4-induced
      hepatocellular damage in rats suggest antioxidant and drug detoxification
      activities. Overall, this study has justified the rationale behind some of the
      medicinal uses of the plant in folklore medicine of Nigeria.

PMID- 20815701
TI  - Antidiabetic effect of Dodonaea viscosa aerial parts in high fat diet and low
      dose streptozotocin-induced type 2 diabetic rats: a mechanistic approach.
AB  - CONTEXT: High fat diet (HFD) and low-dose streptozotocin (STZ) is an ideal model
      for type 2 diabetes mellitus (T2DM) that would closely reflect the natural
      history and metabolic characteristics of human T2DM and is also suitable for
      pharmacological screening. OBJECTIVE: The present study was designed to
      investigate the effect of the water extract (DVW) and the polar fraction of
      ethanol extract (DVE-4) of Dodonaea viscosa (L). Jacq. (Sapindaceae) on
      biochemical parameters in type 2 diabetes induced by a standardized HFD and low
      dose streptozotocin (25 mg/kg) in rats. Further, to elucidate the mode of action
      we evaluated its effects on a battery of targets involved in glucose homeostasis
      (in vitro studies). MATERIALS AND METHODS: Different doses of DVW and DVE-4 were
      administered once daily for two weeks to HFD + STZ diabetic rats. Quantification
      of biomarker quercetin was done using HPLC. RESULTS AND DISCUSSION: Both DVW and
      DVE-4 dose-dependently reduced blood glucose, serum insulin, homeostatic model
      assessment (HOMA), lipid profiles, and significantly improved glucose tolerance
      and HDL-c levels. In addition, the extract and fraction also decreased oxidative
      stress by improving endogenous antioxidants. In different, bioassays, DVW and DVE
      4 showed inhibition of PTP-1B and at a concentration of 10 MUg/mL showed 60 and
      54.2% binding to PPARgamma, respectively. Both extract/fraction exhibited
      stimulation of glucose uptake by skeletal muscles. CONCLUSION: Taken together,
      these results suggest that DVW and DVE-4 inhibits HFD + STZ-induced insulin
      resistance, lipid abnormalities and oxidative stress indicating that these
      effects may be mediated by interacting with multiple targets operating in
      diabetes mellitus.

PMID- 20815702
TI  - Anti-inflammatory activities of essential oils and their constituents from
      different provenances of indigenous cinnamon (Cinnamomum osmophloeum) leaves.
AB  - CONTEXT: Cinnamomum osmophloeum Kaneh. (Lauraceae) is one of the indigenous tree
      species in Taiwan. This tree species has been of interest to researchers because
      the chemical constituents of its essential oil are similar to those of Cinnamomum
      cassia Presl. bark oil, known as cinnamon oil, which is commonly used in foods
      and beverages. OBJECTIVE: The anti-inflammatory activities of the leaf essential
      oils and their major compounds from seven provenances of C. osmophloeum are
      investigated here for the first time. MATERIALS AND METHODS: Chemical
      compositions of hydrodistilled essential oils obtained from C. osmophloeum leaves
      were analyzed by gas chromatography-mass spectrometry (GC-MS), and the effects of
      essential oils on nitric oxide (NO) production in lipopolysaccharide (LPS)
      activated RAW 264.7 macrophages were investigated. RESULTS: The leaf essential
      oils of cinnamaldehyde type and mixed type strongly inhibited NO production, with
      IC(50) values ranging from 9.7-15.5 MUg/mL. Furthermore, trans-cinnamaldehyde is
      responsible for the inhibitory activity of cinnamaldehyde type, and T-cadinol and
      alpha-cadinol are responsible for the inhibitory activity of mixed type.
      DISCUSSION AND CONCLUSION: These findings demonstrate that the leaf essential
      oils and their constituents of C. osmophloeum have excellent anti-inflammatory
      activities and thus have great potential as a source for natural health products.

PMID- 20815703
TI  - Serological correlate of protection against norovirus-induced gastroenteritis.
AB  - BACKGROUND: Norovirus infection is the leading cause of acute nonbacterial
      gastroenteritis. Histoblood group antigens (HBGAs) are host susceptibility
      determinants for Norwalk virus (NV) infection. We hypothesized that antibodies
      that block NV-HBGA binding are associated with protection from clinical illness
      following NV exposure. METHODS: We developed an HBGA blocking assay to examine
      the ability of human serum to block the interaction of NV viruslike particles
      with H type 1 and H type 3 glycans. Serum samples from persons who were
      experimentally challenged with NV were evaluated. RESULTS: There was a high
      correlation between the H type 1 and H type 3 synthetic glycan assays (r = 0.977;
      P < .001); the H type 1 assay had higher quantitative sensitivity (P < .001).
      Among 18 infected secretor-positive individuals, blocking titers peaked by day 28
      after challenge and were higher for individuals who did not develop
      gastroenteritis than for those who developed gastroenteritis on days 0, 14, 28,
      and 180 (P < .05 for each). In addition, 6 of 6 subjects without gastroenteritis
      had measurable prechallenge blocking titers (>25), compared with 2 of 12 subjects
      with gastroenteritis (P = .002). CONCLUSIONS: Blocking antibodies correlate with
      protection against clinical NV gastroenteritis. This knowledge will help guide
      the evaluation of new vaccine strategies and the elucidation of the nature of
      immunity to the virus. Trial registration. ClinicalTrials.gov identifier:
      NCT00138476.

PMID- 20815705
TI  - Pediatric epstein-barr virus carriers with or without tonsillar enlargement may
      substantially contribute to spreading of the virus.
AB  - BACKGROUND: Human-to-human transmission of the persistent infection establishing
      Epstein-Barr virus (EBV) occurs via saliva. Tonsils act as important portal of
      entry and exit of EBV. The contagiousness of pediatric EBV carriers and the role
      played by tonsillar enlargement (TE) are not known. METHODS: We compared EBV
      shedding in mouthwash samples from pediatric EBV carriers with or without TE to
      that in mouthwash samples from pediatric patients with infectious mononucleosis
      (IM), the symptomatic form of primary infection if delayed after the age of 5
      years. EBV DNA was quantified by polymerase chain reaction, and contagiousness
      was assessed using the cord lymphocyte transformation assay. RESULTS: EBV
      carriers with TE shed EBV DNA at an almost similar frequency (although in lower
      amounts) as pediatric patients with acute IM but more frequently (P <.001) and in
      higher amounts (P = .038) than EBV carriers without TE. EBV DNA levels in
      mouthwash samples from EBV carriers with TE mirrored levels in tonsils and
      gradually declined after tonsillectomy. Almost half of the mouthwash samples from
      pediatric EBV carriers contained infectious EBV. CONCLUSIONS: Pediatric EBV
      carriers--in particular, those with TE-may considerably contribute to the
      spreading of EBV in industrialized countries.

PMID- 20815704
TI  - Mice lacking both TNF and IL-1 receptors exhibit reduced lung inflammation and
      delay in onset of death following infection with a highly virulent H5N1 virus.
AB  - BACKGROUND: Highly pathogenic avian influenza viruses of the H5N1 subtype
      continue to cross the species barrier to infect humans and cause severe disease.
      It has been suggested that an exaggerated immune response contributes to the
      pathogenesis of H5N1 virus infection in mammals. In particular, H5N1 virus
      infections are associated with a high expression of the proinflammatory
      cytokines, including interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF
      alpha). METHODS: We investigated the compounding affects of both cytokines on the
      outcome of H5N1 virus disease by using triple mutant mice deficient in 3
      signaling receptors, TNF-R1, TNF-R2, and IL-1-RI. RESULTS: Triple mutant mice
      exhibited reduced morbidity and a significant delay in mortality following lethal
      challenge with a lethal H5N1 virus, whereas no such differences were observed
      with the less virulent A/PR/8/34 (H1N1) virus. H5N1-infected triple mutant mice
      displayed diminished cytokine production in lung tissue and a quantifiable
      decrease of macrophages and neutrophils in the lungs postinfection. Moreover,
      morphometric analysis of airway sections revealed less extensive inflammation in
      H5N1-infected triple mutant mice, compared with infected wild-type mice.
      CONCLUSIONS: The combined signaling from the TNF or IL-1 receptors promotes
      maximal lung inflammation that may contribute to the severity of disease caused
      by H5N1 virus infection.

PMID- 20815707
TI  - Videofluoroscopic and nasendoscopic correlates of speech in velopharyngeal
      dysfunction.
AB  - OBJECTIVE: To compare videonasendoscopy, lateral videofluoroscopy, and perceptual
      speech examination in the assessment of velopharyngeal dysfunction. DESIGN:
      Retrospective observational. SETTING: Multidisciplinary cleft palate team at a
      tertiary academic institution. PATIENTS, PARTICIPANTS: Patients who had undergone
      videonasendoscopy and lateral videofluoroscopy for suspected velopharyngeal
      dysfunction at our center were evaluated. Inclusion required that
      videonasendoscopy, lateral videofluoroscopy, and the perceptual speech exam were
      performed on the same day. A total of 88 patients were analyzed. MAIN OUTCOME
      MEASURE(S): Primary outcome measures included percent closure on
      videonasendoscopy, percent closure on lateral videofluoroscopy, and quantitative
      scores for hypernasal resonance, nasal emission, and facial grimace. Additional
      outcome measures included linear and angular anatomic measurements obtained from
      lateral videofluoroscopy. RESULTS: Moderately strong correlation was found
      between closure estimates of videonasendoscopy and lateral videofluoroscopy (rho
      = .583; p < .001). Lateral videofluoroscopy estimates of closure averaged 11.7%
      higher than videonasendoscopy. Closure correlated moderately with overall speech
      severity (rho = .304; p = .005); whereas, a stronger correlation was seen with
      hypernasal resonance (rho = -.479; p < .001). Patients exhibiting grimace had
      worse closure than those without (79.1% versus 70.7%; p = .035). Movement angle
      of the velum and change in genu angle correlated significantly with closure
      function (rho = -.304; p = .034 and rho = -.395; p < .001, respectively).
      CONCLUSIONS: Videonasendoscopy and lateral videofluoroscopy closure estimates
      correlated moderately. Lateral videofluoroscopy tended to give smaller gap
      estimates. Hypernasal resonance and facial grimace are useful clinical indicators
      of large gap size. Velar movement angle and change in genu angle were identified
      as anatomical correlates of closure function.

PMID- 20815706
TI  - Intracranial volume and whole brain volume in infants with unicoronal
      craniosynostosis.
AB  - OBJECTIVE: Craniosynostosis has been hypothesized to result in alterations of the
      brain and cerebral blood flow due to reduced intracranial volume, potentially
      leading to cognitive deficits. In this study we test the hypothesis that
      intracranial volume and whole brain volume in infants with unilateral coronal
      synostosis differs from those in unaffected infants. DESIGN: Our study sample
      consists of magnetic resonance images acquired from 7- to 72-week-old infants
      with right unilateral coronal synostosis prior to surgery (n  =  10) and age
      matched unaffected infants (n  =  10). We used Analyze 9.0 software to collect
      three cranial volume measurements. We used nonparametric tests to determine
      whether the three measures differ between the two groups. Correlations were
      calculated between age and the three volume measures in each group to determine
      whether the growth trajectory of the measurements differ between children with
      right unicoronal synostosis and unaffected infants. RESULTS: Our results show
      that the three volume measurements are not reduced in infants with right
      unicoronal synostosis relative to unaffected children. Correlation analyses
      between age and various volume measures show similar correlations in infants with
      right unicoronal synostosis compared with unaffected children. CONCLUSIONS: Our
      results show that the relationship between brain size and intracranial size in
      infants with right unicoronal synostosis is similar to that in unaffected
      children, suggesting that reduced intracranial volume is not responsible for
      alterations of the brain in craniosynostosis.

PMID- 20815708
TI  - Prenatal assessment of the antero-posterior jaw relationship in human fetuses:
      from anatomical to ultrasound cephalometric analysis.
AB  - OBJECTIVES: We wished to develop an ultrasound cephalometric analysis,
      particularly of the antero-posterior jaw relationship, to increase the accuracy
      of prenatal diagnosis of retrognathism during the routine midterm test. METHODS:
      Anatomical cephalometric analysis was performed in 18 formalin-fixed human
      fetuses (between 16 and 39 gestational weeks), and ultrasound cephalometry was
      prospectively carried out in 52 pregnant women (21 to 25 gestational weeks). The
      same landmarks were used in the anatomical and ultrasound median sagittal planes
      for comparison. Four cephalometric angles were measured relative to the anterior
      cranial base: alveolar projection of the maxilla and the mandible, chin
      projection, and facial angle. The antero-posterior jaw discrepancy was
      calculated. RESULTS: The projection of the maxilla was similar in the two
      cephalometric analyses (IC [-3.39, 0.23]), whereas the values of the projection
      of the mandible were lower in the ultrasound sample. The slope of the regression
      line of the antero-posterior jaw discrepancy on fetuses' age did not show
      significant differences (IC [-0.05, 1.54]) between anatomical and ultrasound
      cephalometry, although a difference of 3.23 degrees  +/- 0.78 degrees  (IC [1.69,
      4.77]) was observed. Despite this variability, the projections of mandible and
      chin were well determined by the projection of the maxilla both in the anatomical
      and ultrasound sample. CONCLUSIONS: Cephalometric analysis by prenatal sonography
      can be performed to study the antero-posterior jaw relationship. We think that
      this procedure could be useful to improve prenatal diagnosis of retrognathism in
      high-risk pregnancies. Further studies should address the reproducibility and
      accuracy of such analysis.

PMID- 20815709
TI  - Prevalence and severity of obstructive sleep apnea and snoring in infants with
      Pierre Robin sequence.
AB  - OBJECTIVE: To evaluate the prevalence and severity of obstructive sleep apnea in
      infants with Pierre Robin sequence prior to airway intervention and determine
      whether snoring correlates with the presence of obstructive sleep apnea in this
      population. DESIGN: Retrospective case series. SETTING: Urban tertiary care
      teaching hospital. PARTICIPANTS/METHODS: Review of infants with Pierre Robin
      sequence who underwent polysomnography in the first year of life from 2002 to
      2007. Only results from the initial polysomnography were analyzed. A subgroup of
      consecutive prospectively tested patients was also evaluated. RESULTS: A total of
      33 infants with Pierre Robin sequence were identified. Of these, 13 (39%), 11
      girls and two boys, underwent polysomnography in the first year of life. The mean
      age at evaluation was 48 days (range, 7 to 214 days). Seven nonconsecutive and
      six consecutive patients were included, and no significant differences were seen
      between groups. Obstructive sleep apnea was identified in 11 of 13 (85%) infants.
      The mean obstructive apnea-hypopnea index was 33.5 (range, 0 to 85.7).
      Obstructive sleep apnea severity was mild in 2 of 11 (18%), moderate in 3 of 11
      (27%), and severe in 6 of 11 (55%). Mean end-tidal Pco(2) measurements were
      elevated at 59 mm Hg (range, 47 to 76 mm Hg). Mean oxygen saturation nadir was
      decreased at 80% (range, 68% to 93%). Snoring occurred in only 7 of 13 (54%). Of
      the subjects with obstructive sleep apnea, snoring occurred in 6 of 11 (55%).
      CONCLUSION: The high incidence of obstructive sleep apnea in this group suggests
      that polysomnography should be promptly performed in children with Pierre Robin
      sequence. Although snoring was seen in the majority, the absence of snoring did
      not exclude the presence of obstructive sleep apnea.

PMID- 20815710
TI  - Histology and function: analyzing the uvular muscle.
AB  - OBJECTIVE: Virtual surgery and virtual patients necessitate quantitative data on
      the area of interest. The study was conducted to exactly describe the embryonic
      and fetal uvular muscle (MU), relevant for clinical as well as virtual surgery
      and virtual patient generation. METHOD: Serially sectioned viscerocrania of 10
      aborted embryos and fetuses underwent three-dimensional reconstruction to obtain
      detailed anatomic data and perform finite element analyses. RESULTS: The MU was
      paired in 80% of cases, while 20% allowed no clear-cut distinction. The MU merged
      with the levator muscle beneath the palatal aponeurosis without a hard palate
      insertion. Superior longitudinal central fibers ran below the nasal mucosa, and
      few circular peripheral fibers crossed in the central third to the contralateral
      side. This was seen in 30% of the paired muscles and in all cases when no
      differentiation was possible; about 40% to 80% MU fibers crossed to the
      ipsilateral and contralateral palatopharyngeus muscle behind the levator loop. MU
      fibers inserted 60% nasal and 40% oral to the basal membrane at the middle third
      of the macroscopic uvula, made of loose connective tissue and salivary glands.
      The results of the finite element simulation of the uvula showed no distinct
      patterns or distributions of local stress. CONCLUSIONS: Detailed anatomical study
      supported the concept of mediocranial MU repositioning during corrective surgery,
      although the impact is minor to the levator muscle's action. Future mathematical
      models describing effects of such a maneuver should integrate surrounding
      structures.

PMID- 20815711
TI  - Three-dimensional assessment of early surgical outcome in repaired unilateral
      cleft lip and palate: Part 1. Nasal changes.
AB  - OBJECTIVE: To evaluate three-dimensional nasal morphology following primary
      reconstruction in children with unilateral cleft lip and palate relative to
      contemporaneous noncleft data. DESIGN: Prospective, cross-sectional, controlled
      study. SETTING: Glasgow Dental Hospital and School, Faculty of Medicine, Glasgow
      University. PATIENTS AND PARTICIPANTS: Two groups of 3-year-old children (21 with
      unilateral cleft lip and palate and 96 controls) with facial images taken using a
      three-dimensional, vision-based capture technique. METHODS: Three-dimensional
      images of the face were reflected so the cleft was on the left side to create a
      homogeneous group for statistical analysis. Three-dimensional coordinates of
      anthropometric landmarks were extracted from facial images by a single operator.
      A set of linear measurements was used to compare cleft and control subjects on
      right and left sides, adjusting for sex differences. RESULTS: The mean nasal base
      width and the width of the nostril floor on right and left sides differed
      significantly between control and unilateral cleft lip and palate groups. The
      measurements were greater in children with unilateral cleft lip and palate. The
      differences in the mean nasal height and mean nasal projection between the groups
      were not statistically significant. Mean columellar lengths were different
      between the left and right sides in children with unilateral cleft lip and
      palate. CONCLUSIONS: There were significant nasal deformities following the
      surgical repair of unilateral cleft lip and palate.

PMID- 20815712
TI  - The psychosocial effects of cleft lip and palate in non-Anglo populations: a
      cross-cultural meta-analysis.
AB  - OBJECTIVE: A meta-analytic study was conducted to examine the cross-cultural
      psychosocial impact of cleft lip and/or palate in non-Anglo populations. DESIGN:
      A total of 333 citations were initially identified for review using electronic
      and hand-search strategies. Of the six studies that met inclusion criteria, two
      were later excluded due to insufficient data. The four remaining studies
      represented a combined sample size of 2276 adolescents and adults with cleft lip
      and/or palate from China, Hong Kong, Taiwan, and Norway. MAIN OUTCOME MEASURES:
      Effect size using Cohen's d and confidence intervals were estimated using data
      from four studies of empirical, controlled study designs. RESULTS: The magnitude
      of effect sizes indicated that men (d = -0.75) with cleft lip and/or palate in
      non-Anglo cultures are more prone to psychosocial issues than women (d = -0.33).
      Adults (d = -0.50) are more impacted than adolescents (d = -0.04). Overall,
      regardless of age, gender, or culture, individuals with cleft lip and/or palate
      have lower psychosocial development than individuals without cleft lip and/or
      palate (d = -0.42). CONCLUSION: The effects for the cross-cultural comparisons
      were moderated by the age group and gender of the participants; however, most
      studies resulted in negative effect sizes. Health care teams for cleft lip and/or
      palate should recognize the importance of psychological intervention and family
      support in the treatment of all patients with cleft lip and/or palate throughout
      the life span.

PMID- 20815713
TI  - Achieving low cleft palate fistula rates: surgical results and techniques.
AB  - OBJECTIVES: To prospectively evaluate and reduce fistula rate after primary cleft
      palate repair in an academic setting. METHODS: After noting an institutional
      palate fistula rate of 35.8%, when a majority of palatoplasties were performed
      using the Furlow double-opposing Z-plasty, the decision was made to re-evaluate
      the surgical techniques used for palate repair. As part of our re-evaluation,
      Furlow and von Langenbeck repairs were limited to clefts less than 8 mm in width.
      Wider clefts were repaired early in the series with Veau-Wardill-Kilner and later
      with Bardach two-flap palatoplasties. Half of each palate repair was performed by
      the residents. SETTING: Multidisciplinary follow-up was obtained at the
      University of North Carolina Craniofacial Center. RESULTS: A palate fistula was
      noted in 2 (1.6%) out of 126 cleft palate repairs (both fistulas were located at
      the anterior hard palate). A split uvula was identified in 2 of 59 patients where
      the status of the uvula was reported (3.4%). CONCLUSION: This study summarizes
      one of the lowest overall fistula rates reported in the literature. In a tertiary
      care academic setting, plastic surgery residents can actively contribute to
      palatoplasty with a very low fistula rate. Technical keys to achieving low
      fistula rate include skeletonization of the vascular pedicle for medialization of
      the mucoperiosteal flaps, aggressive posterior repositioning of the levator
      muscle, and meticulous two-layer mattress-suture closure. We recommend Furlow
      repair for narrower clefts (less than 8 mm wide at the posterior border of the
      hard palate) and the Bardach two-flap palatoplasty for wider clefts.

PMID- 20815714
TI  - The use of the 5-year-olds' index: comparison between study models and intraoral
      photographs.
AB  - OBJECTIVE: To determine if photographs may be used instead of dental study models
      to assess the outcome of primary surgery in 5- to 6-year-olds who were born with
      complete unilateral cleft lip and palate. DESIGN: Retrospective method comparison
      study. SETTING: Five U.K. cleft units. SUBJECTS: Records of 96 children born with
      complete unilateral cleft lip and palate. METHOD: Dental study models and
      photographs including an overjet measurement taken from both the most prominent
      and retrusive tooth in each case were scored using the 5-year-olds' index.
      RESULTS: There was moderate to very good agreement between the methods of using
      study models or photographs. Intraexaminer agreement was moderate to very good
      for study models. For the photographs it was good to very good. Overall
      interexaminer agreement was moderate for both study models and photographs.
      CONCLUSIONS: When impressions are difficult to obtain, intraoral photographs with
      clinically recorded overjet measurements may be used for the 5-year-olds' index.

PMID- 20815715
TI  - Congenital anomalies associated with cleft lip and palate-an analysis of 1623
      consecutive patients.
AB  - OBJECTIVE: To document the frequency and nature of associated anomalies in cleft
      lip and/or palate patients from a craniofacial center in India. SETTING:
      Craniofacial Surgery & Research Centre, SDM College of Dental Sciences &
      Hospital, Dharwad, India. PATIENTS/PARTICIPANTS: A total of 1623 consecutive
      patients with cleft lip and/or cleft palate treated in a 40-month period. MAIN
      OUTCOME MEASURE: Frequency and nature of associated anomalies, analyzed according
      to the cleft type and principal organ system and/or area affected. RESULTS: The
      overall male to female ratio was 1.8?1. Unilateral cleft lip with cleft palate
      (41%) was the most frequent cleft subtype, followed by cleft lip and/or cleft
      alveolus (33%); isolated submucous cleft palate (1%) was the least frequent. A
      total of 240 (14.8%) patients had associated anomalies, and these were more
      frequent in males (M?F  =  1.4?1). Per patient, anomalies were most frequent in
      the submucous cleft group (mean, 0.53) and least common in the cleft lip with or
      without cleft alveolus (mean, 0.14). Anomalies were most frequent in the facial
      region (21%), followed by the ocular (17%), central nervous (15%),
      gastrointestinal (3%), and urogenital (2%) systems. Thirty-four patients (2%) had
      recognized nonchromosomal syndromes; this was more common in the cleft palate
      group. CONCLUSIONS: Associated anomalies are not uncommon in patients with cleft
      lip and/or palate, though the frequency varies with the cleft type and organ
      system affected.

PMID- 20815716
TI  - Nasopharyngeal airway for management of airway obstruction in infants with
      micrognathia.
AB  - OBJECTIVE: Describe airway management using nasopharyngeal airway in infants.
      DESIGN: Retrospective case series (1996 to 2006). SETTING: Tertiary pediatric
      hospital. PATIENTS, PARTICIPANTS: The craniofacial database of Seattle Children's
      Hospital was searched to identify patients with one of the following diagnoses:
      micrognathia, secondary cleft palate, branchial arch anomalies, Pierre Robin
      sequence (PRS), or velocardiofacial syndrome. Thirty-five (10.9%) of the 320
      infants born between January 1, 1996, and March 31, 2006, identified using the
      criteria listed above were managed with nasopharyngeal airway (NPA) during
      infancy. INTERVENTIONS: Use of NPA. MAIN OUTCOME MEASURE: Summary statistics
      describing the distribution of the infants' demographic characteristics,
      duration, and timing of their NPA placement, need for tracheotomy, feeding
      interventions, and death. RESULTS: Of the 35 patients included in this case
      series, 60% (21) were male. Eighteen (51.4%) patients had the diagnosis of PRS,
      13 (37.1%) had secondary cleft palate and other craniofacial anomalies, and four
      (11.4%) had branchial anomalies and micrognathia (nonsyndromic or syndromic).
      Thirty-one children (88.6%) were born at term. Mean and median age at initial NPA
      placement was 3.2 and 1.3 weeks, respectively; median duration of NPA was 8.0
      weeks. Nine children received tracheotomies. Feeding tubes were required in 85.7%
      of patients. Two children died; however, neither death was attributed to airway
      obstruction or the use of NPA. CONCLUSIONS: NPA is one option in the management
      of patients with craniofacial anomalies and airway obstruction. The majority of
      nonsyndromic PRS patients treated with NPA during infancy did not require airway
      intervention beyond NPA.

PMID- 20815717
TI  - Magnetic resonance imaging for detection of brain abnormalities in fetuses with
      cleft lip and/or cleft palate.
AB  - OBJECTIVE: To determine the prevalence of brain abnormalities identified by
      prenatal imaging of fetuses with cleft lip with or without cleft palate (CL/P) or
      cleft palate only (CP) and to compare with postnatal imaging and neurologic
      evaluation. DESIGN: This was a retrospective review of radiologic images
      (magnetic resonance imaging [MRI] and sonography) of fetuses diagnosed with CL/P
      or CP at the Advanced Fetal Care Center at Children's Hospital Boston between
      2002 and 2008. Images were reviewed for possible brain abnormalities by a
      pediatric radiologist who specializes in this field. Postnatal imaging was also
      assessed whenever available and correlated with clinical findings. SETTING: A
      large, tertiary-care, academic pediatric hospital. POPULATION: One hundred twenty
      six fetuses and 105 corresponding infants. RESULTS: Brain abnormalities were
      found in 8 of 126 fetuses (6.3%) by prenatal MRI. The malformations were corpus
      callosal dysgenesis (n = 3), encephalocele (n = 1), hypoplasia of the cerebellar
      hemispheres or vermis (n = 3), and white matter neuronal migration anomaly (n =
      1). An additional 2 patients were diagnosed with brain abnormalities postnatally
      that had not been detected on prenatal imaging. CONCLUSIONS: The possibility of
      brain anomalies should be assessed in a fetus found to have CL/P or CP by
      sonography and/or MRI. Central nervous system imaging and careful
      neurodevelopmental follow-up is indicated in these infants.

PMID- 20815718
TI  - Orthopedic and orthodontic treatment in central giant cell granuloma treated with
      calcitonin.
AB  - Central giant cell granuloma of the jaw is a benign lesion of unknown etiology
      that occurs with very low frequency. It mainly occurs in children and young
      adults and is more common in the mandible. The most common treatment is surgical
      removal; however, alternative therapies (intralesional injections of
      corticosteroids, interferon alpha, and calcitonin) have been used in order to
      avoid undesirable damage to the jaws and teeth. The lesion may cause root
      resorption, tooth germ displacement, and other dental problems, as well as
      malocclusion that must be treated orthodontically. The orthodontic, orthopedic,
      and calcitonin-based treatments of one of these cases is presented.

PMID- 20815719
TI  - Postoperative wound management after cleft lip surgery.
AB  - OBJECTIVE: Our aim was to describe the postoperative management and wound care
      protocol after primary cleft lip closure, as it has been used in the Bruges Cleft
      and Craniofacial Center at the supraregional teaching hospital AZ St. Jan,
      Bruges, between June 1, 1991, and July 1, 2009. MATERIALS: The postoperative
      management and wound care included the use of a Logan bow, long-acting local
      anesthetic, elbow restraints, antibiotic therapy, crust removal with normal
      saline solution, and a special local wound ointment that was prepared at our
      center. RESULTS: During the last 19 years, 199 unilateral and 103 bilateral cleft
      lip patients have been repaired. 2.6% showed postoperative infection and/or
      dehiscence. One percent required readmission for reoperation. In 1.6%,
      inflammatory reaction was treated with oral antibiotics. CONCLUSION: The specific
      wound dressing ointment, as it is prepared in our department, could meet the
      requirements of primary wound management after cleft lip closure.

PMID- 20815720
TI  - Early consonant production in Swedish infants with and without unilateral cleft
      lip and palate and two-stage palatal repair.
AB  - OBJECTIVE: To investigate consonant production at 12 and 18 months of age
      following early soft palate repair in infants with unilateral cleft lip and
      palate (UCLP), and to compare it with typically developing children without
      clefts. DESIGN: Randomized study with comparison group. PARTICIPANTS: Twenty
      Swedish infants born with UCLP and 21 without clefts (COMP) were included in a
      randomized trial of palatal surgery (Scandcleft project). Soft palate closure was
      completed at age 5 months; hard palate closure was performed in 11 of the infants
      with UCLP at 1 year of age (HPC) and was left open in nine (HPO). METHOD: Audio
      recordings at 12 months (UCLP  =  9, COMP  =  21) and at 18 months (UCLP  =  18,
      COMP  =  21) were phonetically transcribed. Consonant inventory, frequency of
      manner and place of articulation, true canonical babbling (TCB), and impact of
      hearing status were analyzed. RESULTS: At 12 months of age, all children had
      reached the stage of TCB. Mild hearing impairment was significantly correlated
      with fewer consonant types. A lower frequency of dentals and oral stops was found
      in the UCLP group than in the COMP group. However, the number of oral stops was
      high compared with what has been previously reported. CONCLUSIONS: Early soft
      palate closure seems to give a relatively high number of oral stops even with the
      hard palate unrepaired, although with significantly fewer dentals/alveolars than
      are seen in peers without clefts. Differences in consonant inventory were
      correlated with hearing function.

PMID- 20815721
TI  - The relationship between early reading skills and speech and language performance
      in young children with cleft lip and palate.
AB  - OBJECTIVE: To examine the early reading skills of young children with cleft lip
      and palate and to examine the relationship between early reading skills and
      speech and language performance. PARTICIPANTS: A total of 56 children
      participated in the study: 28 children with cleft lip and palate and 28 noncleft
      children matched for age (mean age, 5 years 7 months), gender, and months of
      formal schooling. MAIN OUTCOME MEASURES: The two groups of children were compared
      (t tests) on the Test of Early Reading-3. Pearson product moment correlations
      were performed to examine separately the relationship between early reading
      skills and speech production abilities and between early reading skills and
      receptive and expressive language abilities for the two groups. RESULTS:
      Statistically significant group differences were noted on the Test of Early
      Reading-3. The mean score of 99 obtained by the group of children with cleft lip
      and palate was within normal limits compared with the norms for the Test of Early
      Reading-3; however, 14% of the children with cleft lip and palate scored outside
      the normal range on the Test of Early Reading-3. Statistically significant
      correlations were obtained between early reading skills and speech production
      abilities and between early reading skills and language abilities. CONCLUSIONS:
      Children with cleft lip and palate differed from noncleft peers in speech and
      early reading skills. Children with the most severe speech problems were the
      children with the poorest performance on the Test of Early Reading-3. Management
      of children with cleft lip and palate should include early identification of and
      intervention for delays in speech, language, and reading.

PMID- 20815722
TI  - Prosthetic rehabilitation of a patient with bilateral cleft lip and palate using
      osseointegrated implants and extracoronal resilient attachments: a case report.
AB  - This case study reports on the prosthetic rehabilitation of a patient with an
      unrepaired bilateral cleft lip and palate using osseointegrated implants,
      extracoronal resilient attachments, a combination of metal-ceramic cement
      retained fixed partial restorations, and removable prosthesis. Preoperative
      clinical examination of a 32-year-old woman with bilateral cleft lip and palate
      revealed a large oronasal communication, hyperplastic soft tissue surrounding the
      hard palate defect, and a severely resorbed alveolar ridge. A maxillary obturator
      prosthesis supported by implants and retained with an extracoronal resilient
      attachment was designed to cover the oronasal communication in the hard palate
      and fulfill the patient's functional and aesthetic requirements. The patient has
      been wearing the prosthesis for 1 year. Her speech quality has greatly improved,
      and her aesthetic and functional expectations have been met.

PMID- 20815725
TI  - Submucous cleft palate and velopharyngeal insufficiency: comparison of speech
      outcomes using three operative techniques by one surgeon.
AB  - OBJECTIVE: Our purpose was to compare speech outcomes among three primary
      procedures for symptomatic submucous cleft palate (SMCP): two-flap palatoplasty
      with muscular retropositioning, double-opposing Z-palatoplasty, or pharyngeal
      flap. DESIGN: Retrospective review. SETTING: Tertiary hospital. PATIENTS,
      PARTICIPANTS: All children with SMCP treated by the senior author between 1984
      and 2008. INTERVENTIONS: One of three primary procedures: two-flap palatoplasty
      with muscular retropositioning, double-opposing Z-palatoplasty, or pharyngeal
      flap. MAIN OUTCOME MEASURES: Speech outcome and need for a secondary operation
      were analyzed among procedures. Success was defined as normal or borderline
      competent velopharyngeal function. Failure was defined as persistent borderline
      insufficiency or velopharyngeal insufficiency with recommendation for a secondary
      operation. RESULTS: We identified 58 patients with SMCP who were treated for
      velopharyngeal insufficiency. We found significant differences in median age at
      operation among the procedures (p < .001). Two-flap palatoplasty with muscular
      retropositioning (n = 24), double-opposing Z-palatoplasty (n = 19), and
      pharyngeal flap (n = 15) were performed at a median of 2.5, 3.6, and 9.5 years,
      respectively. There were significant differences in success among procedures (p =
      .018). Normal or borderline competent function was achieved in 6/20 (30%)
      patients who underwent two-flap palatoplasty, 10/15 (67%) following double
      opposing Z-palatoplasty, and 11/12 (92%) following pharyngeal flap. Among
      patients treated with palatoplasty, success was independent of age at operation
      (p = .16). CONCLUSIONS: Double-opposing Z-palatoplasty is more effective than two
      flap palatoplasty with muscular retropositioning. For children older than 4
      years, primary pharyngeal flap is also highly successful but equally so as a
      secondary operation and can be reserved, if necessary, following double-opposing
      Z-palatoplasty.

PMID- 20815726
TI  - Moraxella catarrhalis: an unrecognized pathogen of the oral cavity?
AB  - OBJECTIVE: We investigated the effect of the bacterial flora of the nose and
      throat on the outcome of the initial repairs of the cleft palate in the presence
      of prophylactic antibiotics. DESIGN: A retrospective review of 90 procedures in
      66 patients who had cleft palate repair between April 2005 and June 2007 was
      conducted at Booth Hall Children's Hospital, Manchester, U.K. Both isolated cleft
      palate and cleft lip and palate patients were included. Exclusion criteria
      included syndromic cases, other medical disorders, and revisions of previous
      cleft palate repairs. Nose and throat swabs were taken on admission. Benzyl
      penicillin and flucloxacillin were given perioperatively. The occurrence of
      oronasal fistulas was correlated with the bacteria grown on culture. RESULTS: The
      oronasal fistula rate was 15.9%. The highest fistula rate in procedures with
      positive swabs was seen with Moraxella catarrhalis. CONCLUSIONS: M. catarrhalis
      has not been previously recognized as a pathogen in cleft palate repairs. This
      study demonstrates a higher fistula rate in procedures positive for M.
      catarrhalis. Other factors that may have contributed to the fistula formation
      include the severity of the initial cleft and technical factors. Further study is
      required before a definitive link can be established.

PMID- 20815724
TI  - CRISPLD2 variants including a C471T silent mutation may contribute to
      nonsyndromic cleft lip with or without cleft palate.
AB  - OBJECTIVE: To assess the association between nonsyndromic (NS) cleft lip with or
      without cleft palate (CL(P)) and single-nucleotide polymorphisms (SNPs) within
      the CRISPLD2 gene (cysteine-rich secretory protein LCCL domain containing 2).
      DESIGN: Four SNPs within the CRISPLD2 gene domain (rs1546124, rs8061351,
      rs2326398, rs4783099) were genotyped to test for association via family-based
      association methods. PARTICIPANTS: A total of 5826 individuals from 1331 families
      in which one or more family member is affected with CL(P). RESULTS: Evidence of
      association was seen for SNP rs1546124 in U.S. (p  =  .02) and Brazilian (p  = 
      .04) Caucasian cohorts. We also found association of SNP rs1546124 with cleft
      palate alone (CP) in South Americans (Guatemala and ECLAMC) and combined
      Hispanics (Guatemala, ECLAMC, and Texas Hispanics; p  =  .03 for both
      comparisons) and with both cleft lip with cleft palate (CLP; p  =  .04) and CL(P)
      (p  =  .02) in North Americans. Strong evidence of association was found for SNP
      rs2326398 with CP in Asian populations (p  =  .003) and with CL(P) in Hispanics
      (p  =  .03) and also with bilateral CL(P) in Brazilians (p  =  .004). In
      Brazilians, SNP rs8061351 showed association with cleft subgroups incomplete
      CL(P) (p  =  .004) and unilateral incomplete CL(P) (p  =  .003). Prediction of
      SNP functionality revealed that the C allele in the C471T silent mutation
      (overrepresented in cases with CL(P) presents two putative exonic splicing
      enhancer motifs and creates a binding site AP-2 alpha, a transcription factor
      involved in craniofacial development. CONCLUSIONS: Our results support the
      hypothesis that variants in the CRISPLD2 gene may be involved in the etiology of
      NS CL(P).

PMID- 20815727
TI  - Prevention of retinoic acid-induced early craniofacial abnormalities by vitamin
      B12 in mice.
AB  - OBJECTIVE: The purpose of the present study was to identify the potential effect
      of prenatal vitamin B12 administration on retinoic acid (RA)-induced early
      craniofacial abnormalities in mice and to investigate the possible mechanisms by
      which vitamin B12 reduces malformations. DESIGN: In our study, whole embryo
      culture was used to explore the effect of vitamin B12 on mouse embryos during the
      critical period of organogenesis. All embryos were exposed to 0.4 uM RA and
      different concentrations of vitamin B12 and scored for their growth in the
      branchial region at the end of a 48-hour culture period. The endothelin-1 (ET
      1)/dHAND protein expression levels in the first branchial arch were investigated
      using an immunohistochemical method. RESULTS: In the whole embryo culture, 100
      and 10 uM vitamin B12 dose-dependently prevented branchial region malformations
      and decreased craniofacial defects by 90.5% and 77.3%, respectively. ET-1 and
      dHAND protein levels were significantly increased in vitamin B12-supplemented
      embryos compared to the RA-exposed group in embryonic branchial region.
      CONCLUSIONS: These results suggest that vitamin B12 may prevent RA-induced
      craniofacial abnormalities via prevention of an RA-induced decrease of ET-1 and
      dHAND protein levels in the branchial region during the organogenic period. This
      study may shed new light on preventing craniofacial abnormalities.

PMID- 20815728
TI  - Oral synechia with epithelial cyst in neonate with cleft palate: a case report.
AB  - Cleft palate with oral synechia is a rare congenital deformity that is
      represented in the literature by only a handful of cases. Midline synechia is
      less common than lateral. Failure to recognize and appropriately treat this
      condition has serious implications for neonatal airway management and feeding. We
      present a case of cleft palate with midline subglossopalatal synechia that was
      transferred from an outside institution after a prolonged period of nonsurgical
      management in which the patient ultimately required intubation for respiratory
      distress. Release of the synechia was performed without complications. We review
      the current literature and discuss diagnosis and surgical management of this rare
      condition.

PMID- 20815730
TI  - Primary correction of nasal septal deformity in unilateral clefts during lip
      repair-a long-term study.
AB  - OBJECTIVE: The aim of this study was to assess the long-term effect of primary
      septal correction carried out during lip closure on the nasal septum. MATERIALS,
      SUBJECTS, AND METHODS: Before primary septal correction was introduced, specimens
      from the septal cartilage and the anterior nasal spine of 10 deceased newborns
      and infants were analyzed with the aid of a light microscope to verify the
      presence of any growth zone. The study group comprised 91 children with
      unilateral clefts who had undergone primary lip repair with septal correction.
      The control group comprised 29 children with unilateral clefts operated on
      without primary septal correction. The appearance of the nasal septum was
      assessed on extraoral photographs in the second week of life and then 10 to 14
      years postoperatively. RESULTS: Morphologic examination revealed fibrous
      connective tissue with no signs of growth between the cartilaginous septum and
      bone. At long-term examination, the study group was found to have a nasal septum
      that was straight in 75 (83%), moderately deviated in 14 (15%), and severely
      deviated in two (2%) patients, whereas in the control group, the septum was
      considered straight in four (14%) children, moderately deviated in 11 (38%), and
      severely deviated in 14 (48%). CONCLUSIONS: Primary septal correction may be
      considered safe because no growth zone exists between the septal cartilage and
      the anterior nasal spine. Careful primary nasal septal correction improves nose
      shape in a way that allows normal growth.

PMID- 20815729
TI  - Mothers' and fathers' reports of stress in families of infants with and without
      single-suture craniosynostosis.
AB  - OBJECTIVE: To compare relative levels of stress reported by mothers and fathers
      in families containing infants with and without single-suture craniosynostosis.
      DESIGN: Case-control study. PARTICIPANTS: Mothers and fathers of 246 infants with
      recently diagnosed single-suture craniosynostosis and 253 frequency-matched
      control infants completed the Parenting Stress Index just prior to their infant's
      cranioplastic surgery. Family demographic information and mothers' ratings of the
      severity of their child's single-suture craniosynostosis were obtained. RESULTS:
      Average Parent Domain scores for parents of infants with single-suture
      craniosynostosis differed little from those reported by parents of control
      infants; however, Child Domain scores among parents of infants with single-suture
      craniosynostosis were higher on some subscales, primarily related to unexpected
      infant health and appearance issues. In both groups, fathers reported higher
      Child Domain stress than mothers, and mothers reported higher Parent Domain
      stress than fathers. Case mothers reported greater stress if they perceived their
      child's condition as more noticeable to others. CONCLUSIONS: Prior to cases'
      cranioplastic surgery, parents of children with and without single-suture
      craniosynostosis reported similar levels of stress in relation to their parenting
      roles and the behavioral characteristics of their infants. Visibility of
      condition should be considered a risk for increased stress for mothers of infants
      with single-suture craniosynostosis. Stress differences between mothers and
      fathers were far more discernible than those associated with the presence or
      absence of single-suture craniosynostosis.

PMID- 20815731
TI  - 3D assessment of lip scarring and residual dysmorphology following surgical
      repair of cleft lip and palate: a preliminary study.
AB  - OBJECTIVE: To evaluate lip scarring and the three-dimensional (3D) lip morphology
      following primary reconstruction in children with unilateral cleft lip and palate
      (UCLP) relative to contemporaneous noncleft data. DESIGN: Retrospective, cross
      sectional, controlled study. SETTING: Glasgow Dental Hospital and School,
      University of Glasgow, U.K. PATIENTS AND PARTICIPANTS: Three groups of 10-year
      old children: 51 with UCLP, 43 UCL (unilateral cleft lip), and 68 controls.
      METHODS: Three-dimensional images of the face were recorded using stereo cameras
      on a two-pod capture station, and 3D coordinates of anthropometric landmarks were
      extracted from the facial images. A novel method was applied to quantify residual
      scarring and the associated lip dysmorphologies. The relationships among outcome
      measures were investigated. RESULTS: Residual lip dysmorphologies were more
      pronounced in UCLP cases. The width of the Cupid's bow was increased due to
      lateral displacement of the christa philteri left (cphL) in both UCL and UCLP
      patients. In the upper part of the lip, the nostril base was significantly wider
      in UCLP cases when compared with UCL cases and controls. Scar redness was more
      pronounced in UCL than in UCLP cases. No relationship could be identified between
      lip scarring and other measurements of lip dysmorphology. CONCLUSIONS:
      Stereophotogrammetry, together with associated image analysis, allow early
      detection of residual dysmorphology following cleft repair.

PMID- 20815732
TI  - beta-TCP versus autologous bone for repair of alveolar clefts in a goat model.
AB  - OBJECTIVE: The aim of this study in goats was to test the hypothesis that a novel
      synthetic bone substitute beta tricalcium phosphate (beta-TCP) can work as well
      as autologous bone harvested from the iliac crest for grafting and repair of
      alveolar clefts. DESIGN: Ten adult Dutch milk goats (Capra hircus) were used in a
      split-mouth study design. MAIN OUTCOME MEASURES: Volumetric histologic assessment
      of new bone formation and radiographic measurement of orthodontic movement of
      teeth in a formerly created alveolar cleft. CONCLUSIONS: The synthetic bone
      substitute beta-TCP was shown to result in bone healing similar to that of iliac
      crest bone. The surgical, orthodontic, and histologic results now warrant the
      testing of beta-TCP in the human cleft situation.

PMID- 20815733
TI  - Differential activity for animals and manipulable objects in the anterior
      temporal lobes.
AB  - Neuropsychological evidence has highlighted the role of the anterior temporal
      lobes in the processing of conceptual knowledge. That putative role is only
      beginning to be investigated with fMRI as methodological advances are able to
      compensate for well-known susceptibility artifacts that affect the quality of the
      BOLD signal. In this article, we described differential BOLD activation for
      pictures of animals and manipulable objects in the anterior temporal lobes,
      consistent with previous neuropsychological findings. Furthermore, we found that
      the pattern of BOLD signal in the anterior temporal lobes is qualitatively
      different from that in the fusiform gyri. The latter regions are activated to
      different extents but always above baseline by images of the preferred and of the
      nonpreferred categories, whereas the anterior temporal lobes tend to be activated
      by images of the preferred category and deactivated (BOLD below baseline) by
      images of the nonpreferred category. In our experimental design, we also
      manipulated the decision that participants made over stimuli from the different
      semantic categories. We found that in the right temporal pole, the BOLD signal
      shows some evidence of being modulated by the task that participants were asked
      to perform, whereas BOLD activity in more posterior regions (e.g., the fusiform
      gyri) is not modulated by the task. These results reconcile the fMRI literature
      with the neuropsychological findings of deficits for animals after damage to the
      right temporal pole and suggest that anterior and posterior regions within the
      temporal lobes involved in object processing perform qualitatively different
      computations.

PMID- 20815735
TI  - Factors associated with the occurrence of hearing loss after pneumococcal
      meningitis.
AB  - BACKGROUND: On the basis of a nationwide registration during a 5-year period
      (1999-2003), the frequency and severity of hearing loss was investigated
      retrospectively in 343 consecutive Danish patients who survived pneumococcal
      meningitis, to identify important risk factors (including the pneumococcal
      serotype) for development of hearing loss. METHODS: Results of blood and
      cerebrospinal fluid (CSF) biochemistry, bacterial serotyping, follow-up
      audiological examinations, and medical records were collected, and disease
      related risk factors for hearing loss were identified. The mean pure-tone hearing
      threshold levels were compared with normative data. RESULTS: Of 240 patients
      examined by use of audiometry, 129 (54%) had a hearing deficit, and 50 (39%) of
      these 129 patients were not suspected of hearing loss at discharge from hospital.
      Of the 240 patients, 16 (7%) had profound unilateral hearing loss, and another 16
      (7%) had bilateral profound hearing loss. Significant risk factors for hearing
      loss were advanced age, the presence of comorbidity, severity of meningitis, a
      low CSF glucose level, a high CSF protein level, and a certain pneumococcal
      serotype (P < .05). By applying multivariate logistic regression analysis, we
      found that advanced age, female sex, and a certain serotype were significant risk
      factors, because fewer patients with serotype 6B had hearing loss than did
      patients with serotype 12F (P = .03), which was the most commonly occurring
      serotype. CONCLUSION: Hearing loss is common after pneumococcal meningitis, and
      audiometry should be performed on all those who survive pneumococcal meningitis.
      Important risk factors for hearing loss are advanced age, female sex, severity of
      meningitis, and bacterial serotype.

PMID- 20815734
TI  - Comparison of incidence of bloodstream infection with methicillin-resistant
      Staphylococcus aureus between England and United States, 2006-2007.
AB  - We compared incidence of methicillin-resistant Staphylococcus aureus (MRSA)
      bloodstream infection (BSI) in the United States and England by using population
      based surveillance. The incidence of community-onset MRSA BSI was 6.3-fold higher
      in the United States than in England, whereas the incidence of hospital-onset
      MRSA BSI was similar between the 2 countries.

PMID- 20815736
TI  - Early oseltamivir treatment of influenza in children 1-3 years of age: a
      randomized controlled trial.
AB  - BACKGROUND: Oseltamivir provides modest clinical benefits to children with
      influenza when started within 48 hours of symptom onset. The effectiveness of
      oseltamivir could be substantially greater if the treatment were started earlier
      during the course of the illness. METHODS: We carried out a randomized, double
      blind, placebo-controlled trial of the efficacy of oseltamivir started within 24
      hours of symptom onset in children 1-3 years of age with laboratory-confirmed
      influenza during the seasons of 2007-2008 and 2008-2009. Eligible children
      received either orally administered oseltamivir suspension or a matching placebo
      twice daily for 5 days. The children received clinical examinations, and the
      parents filled out detailed symptom diaries for 21 days. RESULTS: Of 408
      randomized children who received the study drug (oseltamivir, 203, and placebo,
      205), 98 had laboratory-confirmed influenza (influenza A, 79, and influenza B,
      19). When started within 12 hours of the onset of symptoms, oseltamivir decreased
      the incidence of acute otitis media by 85% (95% confidence interval, 25%-97%),
      but no significant reduction was observed with treatment started within 24 hours.
      Among children with influenza A, oseltamivir treatment started within 24 hours
      shortened the median time to resolution of illness by 3.5 days (3.0 vs 6.5 days;
      P = .006) in all children and by 4.0 days (3.4 vs 7.3; P = .006) in unvaccinated
      children and reduced parental work absenteeism by 3.0 days. No efficacy was
      demonstrated against influenza B infections. CONCLUSIONS: Oseltamivir treatment
      started within 24 hours of symptom onset provides substantial benefits to
      children with influenza A infection. Clinical trials registration.
      ClinicalTrials.gov identifier: NCT00593502.

PMID- 20815737
TI  - Influences on human papillomavirus vaccination status among female college
      students.
AB  - OBJECTIVE: In 2006, the Food and Drug Administration (FDA) approved the human
      papillomavirus (HPV) vaccine Gardasil(r) (Merck) for girls and women aged 9-26
      years. Although the vaccine is ideally administered to 11 and 12 year olds,
      college-aged women may be uniquely at risk for HPV due to high rates of sexual
      activity and, thus, serve as an important catch-up population for the HPV
      vaccine. The purpose of this study is to examine factors associated with HPV
      vaccination status among college women. METHODS: In fall 2008, a convenience
      sample of 256 undergraduate women enrolled in an introductory social science
      course at a large, public, urban university in the southeastern United States was
      surveyed. The 30-item paper-and-pencil questionnaire asked for demographic
      information, HPV knowledge, HPV vaccine beliefs, and HPV vaccination status. The
      overall survey response rate was 89.6%. RESULTS: Most women were unmarried/single
      (91.7%), with a mean age of 18.9 years (range 17-42). Race/ethnicity status
      included 73.0% white, 17.5% Hispanic, and 7.7% black/African American. One
      hundred eleven (40.5%) women reported receiving the vaccine. Nonvaccinated women
      were less likely to have heard of the vaccine through a healthcare provider (odds
      ratio [OR] 0.12, 95% confidence interval [CI] 0.04-0.35) or from a family member
      (OR 0.33, 95% CI 0.16-0.68) and more likely to consider a healthcare provider
      recommendation as being only somewhat important (OR 2.91, 95% CI 1.32-6.41) or
      not important at all (OR 5.61, 95% CI 0.44-71.87) vs. very important.
      CONCLUSIONS: Findings suggest that healthcare providers have an important role in
      encouraging HPV vaccination. Continuing education for providers who see
      preadolescent girls in conjunction with a parent or who treat women of college
      age may be a worthwhile endeavor.

PMID- 20815738
TI  - Predicting obstructive sleep apnea among women candidates for bariatric surgery.
AB  - BACKGROUND: More women than men pursue bariatric surgery for treatment of
      obesity. Untreated obstructive sleep apnea (OSA) in bariatric patients increases
      perioperative morbidity and mortality, and, therefore, most bariatric surgeons
      screen for OSA with polysomnography (PSG). We sought to develop a model for
      predicting OSA in women seeking bariatric surgery in order to use this diagnostic
      resource most efficiently. METHODS: We identified 296 women who had PSG in
      preparation for bariatric surgery. Regression and logistic regression analyses
      were used to assess the relationship between history and physical examination
      findings and OSA severity. After developing best statistical models, we
      constructed a summary index to identify patients exceeding clinical thresholds
      for mild (apnea-hypopnea index [AHI] >= 5) and moderate to severe disease (AHI >=
      15). RESULTS: In our sample, most women (86%) had OSA, and more than half (53%)
      had moderate to severe disease. Multiple logistic regression showed that age,
      body mass index (BMI), neck circumference, hypertension, witnessed apneas, and
      snoring predicted AHI. Diabetes mellitus and daytime sleepiness measured with the
      Epworth Sleepiness Scale (ESS) were not significant predictors of OSA. Prediction
      models were statistically significant but had poor specificity for predicting OSA
      severity. CONCLUSIONS: OSA is highly prevalent in symptomatic and asymptomatic
      women planning bariatric surgery for obesity. Best prediction models based on
      clinical characteristics did not predict disease severity under conditions
      superior to those in which they might be applied. In light of the perioperative
      risks associated with OSA in bariatric patients, all women considering bariatric
      surgery for obesity should be evaluated for OSA with PSG.

PMID- 20815739
TI  - Barrier removal in increasing physical activity levels in obese African American
      women with disabilities.
AB  - BACKGROUND: This pilot study examined the effectiveness of a telephone-based
      intervention to increase physical activity in obese African American women with
      mobility disabilities by targeting the removal of barriers to participation.
      METHODS: Severely obese (mean body mass index [BMI] = 49.1 kg.m2) African
      American women (n = 33) with mobility disabilities completed a 6-month telephone
      based physical activity coaching intervention. RESULTS: The major
      environmental/facility barriers at preintervention were cost of the program
      (66.7%), lack of transportation (48.5%), not aware of fitness center in the area
      (45.5%), and lack of accessible facilities (45.5%). The major personal barriers
      were pain (63.6%), don't know how to exercise (45.5%), health concerns (39.4%),
      don't know where to exercise (39.4%), and lack of energy (36.4%). Despite only
      two personal barriers being significantly lower at posttest (don't know where to
      exercise and don't know how to exercise) (p < 0.01), total exercise time
      increased from < 6 minutes/day to 27 minutes/day at posttest (p < 0.001), and
      total physical activity time (structured exercise, leisure, indoor and outdoor
      household activity) increased from 26 minutes/day to 89 minutes/day at posttest
      (p < 0.001). CONCLUSIONS: Interventions aimed at increasing physical activity
      participation among obese African American women with mobility disabilities
      should start with increasing their awareness/knowledge on where and how to
      exercise. Other reported barriers (e.g., cost, transportation, finding an
      accessible facility, health concerns, pain) may not be as critical to
      alter/remove as identifying where participants can exercise (i.e., home,
      outdoors, gym) and providing them with a variety of routines that can be
      performed safely in their desired setting.

PMID- 20815740
TI  - Get on board the medical data train--it is leaving the station: destination 2014.

PMID- 20815742
TI  - User-generated care: the integration of internet-based health information.

PMID- 20815743
TI  - Teleneurology: beyond stroke care.

PMID- 20815744
TI  - Satisfaction with a distance continuing education program for health
      professionals.
AB  - This study assessed differences in program satisfaction among health
      professionals participating in a distance continuing education program by gender,
      ethnicity, discipline, and community size. A one-group posttest design was used
      with a sample of 45,996 participants in the University of Arkansas for Medical
      Sciences, Rural Hospital, Distance Continuing Medical Education Program during
      1995-2007. This program provided 2,219 continuing education programs for
      physicians (n = 7,047), nurses (n = 21,264), allied health (n = 3,230) and dental
      (n = 305) professionals, pharmacists (n = 4,088), administrators (n = 1,211), and
      marketing/finance/human resources professionals (n = 343). These programs were
      provided in Arkansas hospitals, clinics, and area health education centers.
      Interactive video technology and the Internet were used to deliver these
      programs. The program satisfaction instrument demonstrated adequate internal
      consistency reliability (Cronbach's alpha = 0.91) and construct validity.
      Participants had high levels of satisfaction regarding knowledge and skills, use
      of information to enhance patient care, program quality, and convenience of the
      technology (mean total satisfaction score = 4.44, range: 1-5). Results from the t
      test for independent samples and one-way analysis of variance indicated that men
      (p = 0.01), African-Americans and Hispanics (p < 0.01), dental professionals (p <
      0.01), and participants in larger urban communities (population of 75,001
      185,000) (p < 0.01) had significantly greater satisfaction. Nurses and physicians
      had significantly greater satisfaction regarding the use of information in
      practice to enhance patient care (p < 0.01). Results suggest that socioeconomic
      and demographic factors can affect satisfaction with distance continuing
      education programs.

PMID- 20815745
TI  - E-health applications and services for patient empowerment: directions for best
      practices in The Netherlands.
AB  - OBJECTIVE: E-health may enable the empowerment process for patients, particularly
      the chronically ill. However, e-health is not always designed with the
      requirements of patient empowerment in mind. Drawing on evidence-based e-health
      studies, we propose directions for best practices to develop e-health that
      promotes patient empowerment. METHODS: The concept of patient empowerment in the
      Dutch setting is discussed first. The prerequisites for patient empowerment are
      then described and translated into empowerment areas relevant to e-health.
      MATERIALS: We reviewed Dutch e-health studies that provide insights into what
      works, and what does not, in e-health. RESULTS: On the basis of the lessons
      learned from the studies, we propose directions for best practices to develop e
      health that promotes patient empowerment. These directions cover various aspects,
      such as the design and implementation of e-health, its information content and
      usability, awareness, and acceptance. The studies also indicate the difficulty of
      establishing that e-health is really dedicated to patient empowerment.
      CONCLUSIONS: Despite the body of knowledge about patient empowerment, as well as
      the technological visibility of e-health, evidence for best practices in general
      and for patient empowerment in particular is scarce. We call for a more
      systematic evaluation of e-health for patient empowerment and more reliable
      evidence. Beyond the organizational and technical issues involved in e-health,
      there is also a need to demonstrate its practical benefits to patients. The
      Netherlands is active in developing sustainable e-health. National initiatives
      are now in place to support the processes with the aim of establishing the
      required evidence-based best practices.

PMID- 20815746
TI  - The use of transtelephonic loop recorders for the assessment of symptoms and
      arrhythmia recurrence after radiofrequency catheter ablation.
AB  - Radiofrequency catheter ablation (RFA) is an effective treatment of arrhythmias.
      However, patients often remain symptomatic after the procedure. We aimed to
      assess the arrhythmia recurrence after successful RFA in relation to patients'
      symptoms using transtelephonic loop recorders. Thirty-six consecutive patients
      (age 50 +/- 14 years, 17 males/19 females) were enrolled after successful RFA for
      atrioventricular (AV) nodal reentrant tachycardia (n = 21), AV reentrant
      tachycardia (n = 8), atrial tachycardia (n = 2), atrial fibrillation/flutter (n =
      4), and ventricular tachycardia (n = 1). During 23 +/- 6 days of follow-up, 679
      events were recorded, 246 of which were true arrhythmic events, mostly (56%)
      asymptomatic. The vast majority of these true arrhythmic events were due to
      trivial arrhythmias (extrasystoles or sinus tachycardia), equally distributed
      among symptomatic and asymptomatic episodes. Arrhythmia relapse was shown in four
      patients, who had a total of nine episodes, eight of which were symptomatic. No
      high degree AV block was detected. Overall, symptom recurrence had low
      sensitivity (44%) and high specificity (95%) for the detection of any arrhythmia,
      and high sensitivity (89%) but low specificity (58%) for the detection of
      relapse. In conclusion, transtelephonic monitoring was a useful tool for the
      assessment of symptoms after RFA and its use may be reserved for the most
      symptomatic patients to detect a relapse or to reassure them for the benign
      nature of their symptoms.

PMID- 20815747
TI  - Evaluation of data display for patient-oriented electronic record of
      anticoagulant therapy.
AB  - OBJECTIVE: Our aim was to evaluate visualization methods for specific tasks
      performed with personal healthcare e-record systems for lay adults and older
      patients. We investigated common visualization methods for data entry and follow
      up of personal and clinical information for self-control of blood coagulation
      functions. METHODS: Twenty-five old (72.2 +/- 5.5 years) and 25 young (30.4 +/-
      4.9 years) participants completed tasks based on common scenarios, on
      experimental Web sites with hidden tracking programs. Functional parameters
      (time, accuracy), subjective parameters (preference, satisfaction), and
      physiological parameters (heart rate, skin temperature, sweat, respiratory rate,
      and muscle tension) monitored with miniature sensors were used. RESULTS: Total
      time for data entry and information follow-up were significantly longer for older
      compared with younger participants, with no significant differences in accuracy
      (errors), in stress-related physiological parameters, in preferences, or in
      satisfaction between age group. The Menu display was the significantly preferred
      configuration for data entry in both age groups, based on functional,
      physiological, and subjective criteria (p < 0.05, Duncan test). The Calendar
      configuration was significantly preferred for mixed tasks of follow-up and
      information retrieval, in both age groups, based on functional, physiological,
      and subjective criteria (p < 0.05, Duncan test). CONCLUSIONS: Our study supports
      equal capabilities of old and young people to use interactive healthcare systems
      for management of chronic diseases and further encourages using physiological,
      functional, and subjective methods for evaluating personal healthcare records.

PMID- 20815748
TI  - An agile enterprise regulation architecture for health information security
      management.
AB  - Information security management for healthcare enterprises is complex as well as
      mission critical. Information technology requests from clinical users are of such
      urgency that the information office should do its best to achieve as many user
      requests as possible at a high service level using swift security policies. This
      research proposes the Agile Enterprise Regulation Architecture (AERA) of
      information security management for healthcare enterprises to implement as part
      of the electronic health record process. Survey outcomes and evidential
      experiences from a sample of medical center users proved that AERA encourages the
      information officials and enterprise administrators to overcome the challenges
      faced within an electronically equipped hospital.

PMID- 20815749
TI  - A literature review of transmission effectiveness and electromagnetic
      compatibility in home telemedicine environments to evaluate safety and security.
AB  - OBJECTIVE: The objective of this study was to determine already reported cases of
      transmission/reception failure and interferences to evaluate the safety and
      security of the new mobile home telemedicine systems. MATERIALS AND METHODS: The
      literature published in the last 10 years (1998-2009) has been reviewed, by
      searching in several databases. Searches on transmission effectiveness and
      electromagnetic compatibility were made manually through journals, conference
      proceedings, and also the healthcare technology assessment agencies' Web pages.
      RESULTS: Search strategies developed through electronic databases and manual
      search identified a total of 886 references, with 44 finally being included in
      the results. They have been divided by technology in the transmission/reception
      effectiveness studies, and according to the type of medical device in the case of
      electromagnetic interferences studies. CONCLUSIONS: The study reveals that there
      are numerous publications on telemedicine and home-monitoring systems using
      wireless networks. However, literature on effectiveness in terms of connectivity
      and transmission problems and electromagnetic interferences is limited. From the
      collected studies, it can be concluded that there are transmission failures, low
      coverage areas, errors in the transmission of packets, and so on. Moreover, cases
      of serious interferences in medical instruments have also been reported. These
      facts highlight the lack of studies and specific recommendations to be followed
      in the implementation of biomonitoring systems in domestic environments using
      wireless networks.

PMID- 20815750
TI  - Development of short message service application for patient-provider
      communication in clinical psychiatry.
AB  - This prospective study is the first one of its kind carried out in Finland, in
      which a simple technological platform was developed to merge traditional text
      messaging with an electronic patient information database. The technology has
      been tested for relaying two-way treatment messages in psychiatry provided by a
      central hospital offering secondary healthcare. Text messaging was found to be
      particularly well suited for young people who have to travel to the outpatient
      clinic over long distances or who face the risk of social exclusion. According to
      clinicians, the text message reminders sent between the visits, which take place
      every 1-2 months, can encourage the young people in question to stay in touch
      more frequently, which will help to improve their relationship with the hospital
      staff. The project is still in the pilot stage, and so far the most important
      results concern the development of the operating culture and, surprisingly
      enough, legal aspects. From the legal point of view, the hospital had to equate
      text messages with phone communications. For this reason, it was not possible to
      put the text messages into a separate register and they have not been archived
      either. The success or failure of the new innovative healthcare solution may,
      therefore, depend on both technological aspects and legal factors.

PMID- 20815751
TI  - Impact of blood pressure telemonitoring on hypertension outcomes: a literature
      review.
AB  - We searched five databases (PubMed, CINAHL, PsycINFO, EMBASE, and ProQuest) from
      1995 to September 2009 to collect evidence on the impact of blood pressure (BP)
      telemonitoring on BP control and other outcomes in telemonitoring studies
      targeting patients with hypertension as a primary diagnosis. Fifteen articles met
      our review criteria. We found that BP telemonitoring resulted in reduction of BP
      in all but two studies; systolic BP declined by 3.9 to 13.0 mm Hg and diastolic
      BP declined by 2.0 to 8.0 mm Hg across these studies. These magnitudes of effect
      are comparable to those observed in efficacy trials of some antihypertensive
      drugs. Although BP control was the primary outcome of these studies, some
      included secondary outcomes such as healthcare utilization and cost. Evidence of
      the benefits of BP telemonitoring on these secondary outcomes is less robust.
      Compliance with BP telemonitoring among patients was favorable, but compliance
      among participating healthcare providers was not well documented. The potential
      role of BP telemonitoring in the reduction of BP is discussed and suggestions on
      priority populations that can benefit from this technology are presented.

PMID- 20815752
TI  - Recruitment challenges and strategies in a home-based telehealth study.
AB  - The difficulty in recruiting subjects for home-based telehealth research is well
      documented. This article shares the recruitment statistics and experiences in the
      Assessment of Caregivers for Team Intervention via Videophone Encounters pilot
      study, a home-based telehealth intervention. The study obtained 83% of the
      desired sample. Challenges included issues with initial inclusion criteria,
      weather-related problems, timely referrals and follow-up, the enrollment process,
      the need for multiple visits, and unforeseen cases of multiple caregivers.
      Detailed monitoring and tracking of recruitment statistics and immediate response
      to overcome challenges were critical to the eventual recruitment success.
      Strategies included the reallocation of resources to add a second research site,
      adjustments in inclusion criteria, process improvement with the hospice
      admissions process, and strategies to address staff gate-keeping. Recruitment
      continues to be an important barrier to home-based telehealth research and the
      sharing of recruitment statistics, challenges, and strategies can be beneficial.
      Gathering of recruitment data is a critical component of pilot studies, which
      assists in the development of successful randomized clinical trials for future
      home-based telehealth research.

PMID- 20815755
TI  - Public partnerships for a vision for women's health research in 2020.

PMID- 20815756
TI  - Earlier stage at diagnosis and improved survival among Medicare HMO patients with
      breast cancer.
AB  - OBJECTIVE: We sought to evaluate differences in the stage at diagnosis and the
      survival of breast cancer patients enrolled in two different Medicare healthcare
      delivery systems: fee for service (FFS) and health maintenance organizations
      (HMO). METHODS: We used a linkage of two national databases, the Medicare
      database from the Centers for Medicare and Medicaid Services (CMS), and the
      National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results
      (SEER) program database, to evaluate differences in demographic data, stage at
      diagnosis, and survival in patients with breast cancers over the period 1985
      2001. RESULTS: Medicare patients enrolled in HMOs were diagnosed at an earlier
      stage of diagnosis than FFS patients. HMO patients diagnosed with breast cancer
      had improved survival, and these differences remained even after controlling for
      potential confounders. Specifically, breast cancer patients enrolled in HMOs had
      9% increased probability of survival (hazard ratio [HR] 0.91, 95% confidence
      interval [CI] 0.88-0.93) than their counterparts enrolled in FFS. These findings
      persisted even when patients had a cancer diagnosis before their breast cancer.
      CONCLUSIONS: Improved survival among breast cancer patients in HMOs compared with
      FFS is likely due to a combination of factors, including but not limited to
      earlier stage at the time of diagnosis.

PMID- 20815757
TI  - Totally tubeless percutaneous nephrolithotomy: is it safe and effective in
      preschool children?
AB  - BACKGROUND AND PURPOSE: After the introduction of tubeless percutaneous
      nephrolithotomy (PNL), many studies conducted in adult patients have confirmed
      its efficacy and safety. There are limited studies reporting that tubeless PNL
      can be safely applied in children, however. Furthermore, there are no reports
      that evaluate the use of totally tubeless PNL in children. The present study
      evaluates the results of totally tubeless PNL in preschool children. PATIENTS AND
      METHODS: The data of children seen in our clinic who were considered suitable for
      totally tubeless PNL were analyzed. Of 16 children, 8 patients underwent totally
      tubeless PNL (group 1) and 8 standard PNL (group 2). The two groups of patients
      were compared with regard to length of hospitalization, analgesic requirements,
      transfusion rates, hemoglobin (Hb) decrease, and immediate, early, and late
      complications. RESULTS: The mean ages of the patients were 56.6 months (9-84 mos)
      and 56.0 months (5-84 mos), and the mean follow-up was 21.5 months (3-44 mos) and
      43.4 months (36-54 mos) in groups 1 and 2, respectively. Both groups were similar
      with regard to age, stone size, Hb change, and complications. Although operation
      duration, hospitalization period, and analgesic requirement were less in the
      totally tubeless PNL group, these differences were not statistically significant.
      CONCLUSIONS: The latest application of PNL, totally tubeless PNL, is also a safe
      and effective procedure in very small children if they are selected properly and
      if the surgeon has sufficient experience with the procedure. More studies with a
      higher number of participants are needed, however, to confirm that totally
      tubeless PNL increases the comfort of pediatric patients, decreases their
      hospitalization period, and is more economical.

PMID- 20815758
TI  - Glycopeptide vs. non-glycopeptide antibiotics for prophylaxis of surgical site
      infections: a systematic review.
AB  - BACKGROUND: Patients receive prophylactic antibiotics against surgical site
      infections (SSIs) before or during many procedures. Glycopeptide antibiotics are
      effective against most strains of methicillin-resistant Staphylococcus aureus
      (MRSA), but their wider use risks increasing resistance. Our objective was to
      review the evidence for clinical effectiveness that might help to determine
      whether there is a threshold of MRSA prevalence at which switching from non
      glycopeptide to glycopeptide antibiotic prophylaxis might be justified. METHODS:
      We performed a systematic review of randomized trials comparing a glycopeptide
      with an alternative antibiotic regimen for SSI prophylaxis in adults undergoing
      clean or clean-contaminated surgical procedures. The evidence was used to inform
      development of a decision-analytic model. We subsequently updated the review to
      May 2008. RESULTS: Fourteen studies were identified that provided evidence
      concerning clinical effectiveness. The studies were too heterogeneous clinically
      for meta-analysis. Only one of 12 trials found that glycopeptides reduced SSIs
      significantly at 30 days compared with non-glycopeptide antibiotics. Of the two
      trials that reported on MRSA infection, neither found a significant difference
      between glycopeptide and comparator drugs. CONCLUSIONS: This systematic review
      did not find any evidence to support the use of glycopeptides in preference to
      other antibiotics for the prevention of MRSA infections and SSIs. The limitations
      of the evidence make it difficult to identify a threshold at which a switch from
      non-glycopeptide to glycopeptide prophylaxis should be recommended. Given the
      difficulties of addressing this issue through randomized trials, further research
      should focus on hospital infection control policies, MRSA screening, and the
      isolation and treatment of anyone infected with MRSA prior to surgery.

PMID- 20815759
TI  - Novel in vitro model for assessing susceptibility of synthetic hernia repair
      meshes to Staphylococcus aureus infection using green fluorescent protein-labeled
      bacteria and modern imaging techniques.
AB  - BACKGROUND: Mesh infection complicating hernia repair is a major cause of patient
      morbidity and results in substantial healthcare expenditures. The various
      constructs of prosthetic mesh may alter the ability of bacteria to attach and
      form a biofilm. Few data exist evaluating biofilm formation. Using the Maestro in
      Vivo Imaging System (CRi, Inc., Woburn, MA) to detect green fluorescent protein
      (GFP)-expressing Staphylococcus aureus, we studied the ability of synthetic mesh
      to withstand bacterial biofilm formation in an in vitro model. METHODS: We
      included four meshes: Polypropylene (PP), polypropylene/expanded PTFE (PX),
      compressed PTFE (cPTFE), and polyester/polyethylene glycol and collagen hydrogel
      (PE). Five samples of each mesh were exposed to GFP-expressing S. aureus for 18 h
      at 37 degrees C. Next, green fluorescence was measured using the Maestro Imaging
      System, with the results expressed in relative fluorescence units (RFU),
      subtracting the fluorescence of uninfected mesh (control). Each mesh subsequently
      underwent sonication and quantitative culture of the released bacteria, with the
      results expressed in colony-forming units (CFU). Analysis of variance was
      performed to compare the mean values for the different meshes. RESULTS: There was
      a statistically significant difference in bacterial fluorescence for the four
      meshes: PE (49.9 +/- 25.5 [standard deviation] RFU), PX (30.8 +/- 9.4 RFU), cPTFE
      (10.1 +/- 4.0 RFU), and PP (5.8 +/- 7.5 RFU)(p = 0.001). Bacterial counts also
      were significantly different: PE (2.2 * 10(8) CFU), PX (8.6 * 10(7) CFU), cPTFE
      (3.7 * 10(7) CFU), and PP (9.1 * 10(7) CFU)(p < 0.001). CONCLUSION: Using novel
      imaging technology, this study documented significantly different amounts of S.
      aureus biofilm formation and proliferation on different mesh constructs, with
      good agreement between imaging and culture results. A multifilament woven mesh
      (PE) had the highest degree of biofilm formation. These findings are being
      evaluated in a clinical infection model.

PMID- 20815760
TI  - Diversity in antibody-based approaches to non-Hodgkin lymphoma.
AB  - Non-Hodgkin lymphoma (NHL) remains one of the most common cancers in the US, with
      survival dependent on the type and stage of disease. B-cell lymphomas account for
      approximately 85% of all cases of NHL, and are commonly treated with
      chemotherapy, or monoclonal antibodies (mAbs) that target CD20 antigens on the
      surface of malignant tumors. The use of mAbs, either as single agents or in
      combination with chemotherapy, has made a huge impact on NHL survival rates.
      Rituximab remains the most commonly used and established mAb, and is used in a
      wide range of NHLs, but does not produce an effective therapeutic response in all
      patients. Novel therapeutics with enhanced binding affinity or alternative
      antigen targets are currently in development and in some cases have demonstrated
      improved efficacy over currently available treatments. Radioimmunotherapy has
      been included in transplant conditioning regimens to improve long-term disease
      control while limiting toxicity. These regimens have been safe, effective, and
      feasible, and are therefore promising for patients who cannot tolerate high-dose
      chemotherapy and/or total body irradiation.

PMID- 20815761
TI  - Targeting the microenvironment.
AB  - The microenvironment in which cancer arises plays a critical role in
      tumorigenesis. Although previously regarded as an innocent bystander, evidence
      has accumulated over the past 10 years that the microenvironment contributes to
      tumor growth and progression by providing nutrients and survival signals, and
      protecting the tumor from normal immune responses and anticancer drugs. Exactly
      how normal stromal cells, whose function should be to suppress malignant growth,
      become co-opted into facilitating tumor development is only just beginning to be
      understood, but a complex story is emerging wherein tumor and stromal cells
      appear to co-evolve. A better understanding of tumor-stromal interactions and the
      molecular alterations that result in stromal dysfunction may help to identify
      patients who will benefit from either more aggressive or risk-adapted therapy
      regimens, and/or novel compounds that disrupt the tumor microenvironment and re
      establishing normal control mechanisms.

PMID- 20815762
TI  - Differential relationships between anthropometry measures and cardiovascular risk
      factors in boys and girls.
AB  - OBJECTIVES: The aim of the study was to compare commonly used anthropometry for
      cardiovascular risk factors in 14-year-olds. METHODS: A total of 1 149 children
      of an Australian pregnancy (Raine) cohort with recruitment 1989-1991 were
      assessed for anthropometry and fasting lipids, insulin, and blood pressure.
      RESULTS: There were significant distinctions in the associations between
      anthropometry and groups of cardiovascular risk factors. These distinctions
      differed by gender. Insulin resistance, triglycerides, C-reactive protein levels,
      low density lipoprotein (LDH)/high density lipoprotein (HDL) and total/HDL
      cholesterol ratios had the strongest association with waist, waist/height ratio
      and body mass index. By contrast, in boys, height was the strongest independent
      predictor (in a negative direction) of total and LDL-cholesterol. Blood pressure
      and uric acid was most strongly correlated with body weight and height (heavier
      and taller boys). Taller male adolescents had highest blood pressures and lowest
      cholesterol levels. CONCLUSIONS: No single adolescent anthropometric measure best
      predicted all cardiovascular risk factors. Each measure showed distinct
      relationships with specific groups of risk factors. Contrasting associations may
      reflect different pathogenesis by which gender, puberty, and adiposity affect
      metabolic risk. No single anthropometric measurement in childhood would appear to
      be superior or sufficient when investigating the developmental origins of
      cardiovascular health and related metabolic disease.

PMID- 20815763
TI  - Breast milk and complementary food intake in Brazilian infants according to socio
      economic position.
AB  - OBJECTIVE: (a) To compare breast milk and complementary food intake between
      breast-fed infants from high and low socio-economic status (SES) aged 8 months of
      age; (b) To compare these intakes with PAHO/WHO recommendations. METHODS: Cross
      sectional, community-based study in Pelotas, Brazil. Breast milk and
      complementary food intake were compared between 8-month-old infants from high
      (n=35) and low SES (n=30). Breast milk intake was measured using the 'dose-to-the
      mother' deuterium-oxide turnover method; complementary food intake was assessed
      using a questionnaire and by 24 hours food weighing. RESULTS: Energy intake from
      breast milk (51.1 +/- 26.4 kcal/kg/d) was not different between social groups,
      being in line with current recommendations. However, energy intake from
      complementary foods (34.5 +/- 22.7 kcal/kg/d) and from milk, including breast
      milk, cow's milk and formula (60.1 +/- 19.6 kcal/kg/d), were significantly higher
      than recommendations. Total energy intake was 20% higher than recommended (93.3
      +/- 24.4 versus 77.3 kcal/kg/day, p<0.001). This was mainly due to a high intake
      of complementary foods and addition of cow's milk to breast milk. Introduction of
      complementary foods before 6 months was common. In the high SES group, more
      infants consumed vegetables (p=0.005) and fruit (p=0.020), whereas fats and sugar
      tended to be consumed less frequently (p=0.05 and p=0.17, respectively).
      CONCLUSIONS: Feeding habits deviate from PAHO/WHO recommendations, especially for
      infants of lower SES. Of main concern are the high-energy intake and early
      introduction of cow's milk and complementary foods. This may be important in view
      of metabolic programming and the development of obesity and associated diseases
      later in life.

PMID- 20815764
TI  - Recent advances in hydrogen research as a therapeutic medical gas.
AB  - Recent basic and clinical research has revealed that hydrogen is an important
      physiological regulatory factor with antioxidant, anti-inflammatory and anti
      apoptotic protective effects on cells and organs. Therapeutic hydrogen has been
      applied by different delivery methods including straightforward inhalation,
      drinking hydrogen dissolved in water and injection with hydrogen-saturated
      saline. This review summarizes currently available data regarding the protective
      role of hydrogen, provides an outline of recent advances in research on the use
      of hydrogen as a therapeutic medical gas in diverse models of disease and
      discusses the feasibility of hydrogen as a therapeutic strategy. It is not an
      overstatement to say that hydrogen's impact on therapeutic and preventive
      medicine could be enormous in the future.

PMID- 20815765
TI  - Endothelial NOS-derived nitric oxide prevents injury resulting from reoxygenation
      in the hypoxic lung.
AB  - To date, the role that NO derived from endothelial NO synthase (eNOS) plays in
      the development of the injuries occurring under hypoxia/reoxygenation (H/R) in
      the lung remains unknown and thus constitutes the subject of the present work. A
      follow-up study was conducted in Wistar rats submitted to H/R (hypoxia for 30
      min; reoxygenation of 0 h, 48 h and 5 days), with or without prior treatment
      using the eNOS inhibitor L-NIO (20 mg/kg). Lipid peroxidation, apoptosis, protein
      nitration and NO production (NOx) were analysed. The results showed that L-NIO
      administration lowered NOx levels in all the experimental groups. Contrarily, the
      lipid peroxidation level and the percentage of apoptotic cells rose, implying
      that eNOS-derived NO may have a protective effect against the injuries occurring
      during H/R in the lung. These findings could open the possibility of future
      studies to design new therapies for this type of hypoxia based on NO
      pharmacology.

PMID- 20815766
TI  - A novel analytical method to evaluate directly catalase activity of
      microorganisms and mammalian cells by ESR oximetry.
AB  - Electron spin resonance (ESR) oximetry technique was applied for analysis of
      catalase activity in the present study. Catalase activity was evaluated by
      measuring oxygen from the reaction between hydrogen peroxide (H(2)O(2)) and
      catalase-positive cells. It was demonstrated that the ESR spectra of spin-label
      probes, 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL), 4-oxo-2,2,6,6
      tetramethyl-1-piperidinyloxy (4-oxo-TEMPO) and 4-maleimido-2,2,6,6-tetramethyl-1
      piperidinyloxy (4-maleimido-TEMPO) in the presence of H(2)O(2) were broadened
      with the concentrations of catalase. It was possible to make a calibration curve
      for catalase activity by peak widths of the spectra of each spin-label probe,
      which are broadened dependently on catalase concentrations. The broadened ESR
      spectra were also observed when the catalase-positive micro-organisms or the
      mammalian cells originally from circulating monocytes/macrophages were mixed with
      TEMPOL and H(2)O(2). Meanwhile, catalase-negative micro-organisms caused no
      broadening change of ESR spectra. The present study indicates that it is possible
      to evaluate directly the catalase activity of various micro-organisms and
      mammalian cells by using an ESR oximetry technique.

PMID- 20815767
TI  - Molecular mechanisms of Id2 down-regulation in rat liver after acetaminophen
      overdose. Protection by N-acetyl-L-cysteine.
AB  - Id2 is a pleiotropic protein whose function depends on its expression levels. Id2
      deficient cells show increased cell death. This study explored the molecular
      mechanisms for the modulation of Id2 expression elicited by GSH and oxidative
      stress in the liver of acetaminophen (APAP)-intoxicated rats. APAP-overdose
      induced GSH depletion, Id2 promoter hypoacetylation, RNApol-II released and,
      therefore, Id2 down-regulation. Id2 expression depends on c-Myc binding to its
      promoter. APAP-overdose decreased c-Myc content and binding to Id2 promoter.
      Reduction of c-Myc was not accompanied by decreased c-myc mRNA, suggesting a
      mechanism dependent on protein stability. Administration of N-acetyl-cysteine
      prior to APAP-overload prevented GSH depletion and c-Myc degradation.
      Consistently, c-Myc was recruited to Id2 promoter, histone-H3 was
      hyperacetylated, RNApol II was bound to Id2 coding region and Id2 repression
      prevented. The results suggest a novel transcriptional-dependent mechanism of Id2
      regulation by GSH and oxidative stress induced by APAP-overdose through the
      indirect modulation of the proteasome pathway.

PMID- 20815768
TI  - Characterization of hydrophobic interaction and antioxidant properties of the
      phenothiazine nucleus in mitochondrial and model membranes.
AB  - The antioxidant properties of the phenothiazine nucleus (PHT) associated with
      mitochondrial membranes and liposomes were investigated. PHT exhibited
      hydrophobic interaction with lipid bilayers, as shown by the quenching of excited
      states of 1-palmitoyl-2[10-pyran-1-yl)]-decanoyl-sn-glycero-3-phophocholine
      (PPDPC) incorporated in phosphatidylcholine/phosphatidylethanolamine/cardiolipin
      liposomes, observed even in high ionic strength; and by the spectral changes of
      PHT following the addition of mitochondrial membranes. Inserted into bilayers, 5
      microM PHT was able to protect lipids and cytochrome c against pro-oxidant agents
      and exhibited spectral changes suggestive of oxidative modifications promoted by
      the trapping of the reactive species. In this regard, PHT exhibited the ability
      to scavenge DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) free radical. PHT was
      also able to protect rat liver mitochondria against peroxide- and iron-induced
      oxidative damage and consequent swelling. At the concentration range in which the
      antioxidant properties were observed, PHT did not cause alterations in the
      membrane structure and function. This study contributes to the comprehension of
      the correlation structure and function of phenothiazines and antioxidant
      properties.

PMID- 20815769
TI  - Does radiotherapy increase oxidative stress? A study with nasopharyngeal cancer
      patients revealing anomalies in isoprostanes measurements.
AB  - This study aimed to examine if exposure to ionizing radiation during clinical
      radiotherapy (RT) causes increased oxidative damage. Seven patients with
      nasopharyngeal cancer (NPC) who underwent RT took part in this controlled-trial
      study. Blood and urine samples were obtained for F(2)-isoprostanes (F(2)-IsoPs)
      measurement. Urinary F(2)-IsoPs levels were elevated pre-treatment and remained
      high (but did not increase) during treatment, but decreased to the normal range
      after treatment. Plasma F(2)-IsoPs decreased significantly after the start of
      treatment before rising midway through treatment. Levels decreased significantly
      to below baseline following treatment. However, the patients were observed to
      have substantially lower levels of plasma esterified arachidonic acid (AA)
      residues than controls. The data shows that NPC is associated with elevated F(2)
      isoprostanes in urine and in plasma after correction for decreased AA levels. RT
      did not increase these levels and, indeed, was associated with falls in F(2)
      IsoPs. The validity and usefulness of correction of plasma F(2)-IsoPs for lowered
      AA levels is discussed.

PMID- 20815770
TI  - Novel polyhydroxylated fullerene suppresses intracellular oxidative stress
      together with repression of intracellular lipid accumulation during the
      differentiation of OP9 preadipocytes into adipocytes.
AB  - Along with differentiation of mouse stromal preadipocytes OP9 into adipocytes,
      intracellular ROS, especially superoxide anion radicals detected by NBT reduction
      assay, were found to appreciably increase, mainly in cytoplasmic area,
      parallelling with increases in intracellular lipid-droplet accumulation, whereas
      undifferentiated OP9 cells kept lower levels of ROS and lipid-droplets. beta
      Carotene bleaching assay showed that super-highly hydroxylated fullerene (SHH-F;
      C(60) (OH)(44)) exerted higher antioxidant ability than highly hydroxylated
      fullerene (HH-F; C(60) (OH)(32-34)) or lowly hydroxylated fullerene (LH-F; C(60)
      (OH)(6-12)). Differentiation-dependent lipid-droplet accumulation was suppressed
      by SHH-F or HH-F more efficiently than LH-F. Furthermore, SHH-F significantly
      repressed intracellular ROS generation accompanied by adipocyte differentiation.
      Thus, lipid-droplet accumulation was shown to positively correlate with ROS upon
      the differentiation of OP9 preadipocytes into adipocytes and SHH-F significantly
      suppressed intracellular ROS together with repression of intracellular lipid
      accumulation.

PMID- 20815771
TI  - The antioxidant edaravone attenuates ER-stress-mediated cardiac apoptosis and
      dysfunction in rats with autoimmune myocarditis.
AB  - Experimental autoimmune myocarditis (EAM) is mediated by myocardial infiltration
      by myosin-specific T-cells secreting inflammatory cytokines. In this study, rat
      models of EAM were prepared by injection with porcine cardiac myosin. One week
      after immunization, edaravone was administered intraperitoneally at 3 or 10
      mg/kg/day to rats for 2 weeks. Cardiac function was measured by haemodynamic and
      echocardiographic studies and TUNEL assay was performed. Left ventricular (LV)
      expression of NADPH oxidase sub-units (p47(phox) and p67(phox)), pro-inflammatory
      cytokines (TNF-alpha), endoplasmic reticulum (ER) stress signalling proteins
      (GRP78, caspase-12 and GADD153) and mitogen-activated protein kinase (MAPK)
      family proteins (phospho-p38 MAPK and phospho-JNK) were measured by western
      blotting. Edaravone improved LV function in a dose-dependent manner. Central
      venous pressure was significantly low and LV ejection fraction and fractional
      shortening was significantly high in edaravone groups compared with those in the
      vehicle group. In addition, edaravone treatment down-regulated LV expressions of
      p47(phox), TNF-alpha, GADD153, phospho-p38 MAPK and phospho-JNK. Furthermore, the
      LV expressions of p67(phox), GRP78, caspase-12 and TUNEL-positive cells of rats
      with EAM treated with edaravone were significantly low compared with those of the
      vehicle group. These findings suggest that edaravone ameliorated the progression
      of EAM by inhibiting oxidative and ER stress and, subsequently, cardiac
      apoptosis.

PMID- 20815772
TI  - Reactive oxygen species (ROS) reduce the expression of BRAK/CXCL14 in human head
      and neck squamous cell carcinoma cells.
AB  - The present study investigated the effects of oxidative stress induced by
      reactive oxygen species (ROS), such as hydrogen peroxide (H(2)O(2)) and hydroxyl
      radical (HO(*)), on the expression of both BRAK , which is also known as non-ELR
      motif angiostatic CXC chemokine ligand 14 (CXCL14), in head and neck squamous
      cell carcinoma (HNSCC) cells. When HNSCC cells were cultured in the presence of
      ROS, the expression of BRAK was significantly decreased whereas that of IL-8 was
      increased. Interestingly, the effects on the expression of both genes in HNSCC
      cells were much greater with HO(blacksquare, square, filled) than with H(2)O(2).
      The effects of ROS on both BRAK and IL-8 expression were attenuated by pre
      treatment with N-acetyl-L-cysteine (NAC), epidermal growth factor receptor
      (EGFR), and mitogen-activated protein kinase (MAPK) inhibitors. These results
      indicate that oxidative stress induced by H(2)O(2) or HO(*) stimulates
      angiogenesis and tumuor progression by altering the gene expression of BRAK and
      IL-8 via the EGFR/MEK/ERK pathway in human HNSCC cells.

PMID- 20815773
TI  - Methyleugenol reduces cerebral ischemic injury by suppression of oxidative injury
      and inflammation.
AB  - The present study tested the cytoprotective effect of methyleugenol in an in vivo
      ischemia model (i.e. middle cerebral artery occlusion (MCAO) for 1.5 h and
      subsequent reperfusion for 24 h) and further investigated its mechanism of action
      in in vitro cerebral ischemic models. When applied shortly after reperfusion,
      methyleugenol largely reduced cerebral ischemic injury. Methyleugenol decreased
      the caspase-3 activation and death of cultured cerebral cortical neurons caused
      by oxygen-glucose deprivation (OGD) for 1 h and subsequent re-oxygenation for 24
      h. Methyleugenol markedly reduced superoxide generation in the ischemic brain and
      decreased the intracellular oxidative stress caused by OGD/re-oxygenation. It was
      found that methyleugenol elevated the activities of superoxide dismutase and
      catalase. Further, methyleugenol inhibited the production of nitric oxide and
      decreased the protein expression of inducible nitric oxide synthase.
      Methyleugenol down-regulated the production of pro-inflammatory cytokines in the
      ischemic brain as well as in immunostimulated mixed glial cells. The results
      indicate that methyleugenol could be useful for the treatment of
      ischemia/inflammation-related diseases.

PMID- 20815775
TI  - Dietary modulation of oxidative stress in chronic obstructive pulmonary disease
      patients.
AB  - A total of 267 clinically stable chronic obstructive pulmonary disease (COPD)
      patients provided complete data about diet and oxidative stress markers in order
      to assess the relationship between antioxidant rich food groups and nutrients,
      and serum markers of oxidative stress in COPD. Dietary data of the last 2 years
      was assessed using a validated food frequency questionnaire (122 items). Levels
      of carbonyls, nitrotyrosine, malondialdehyde and reduced glutathione (GSH) were
      measured in serum. Vitamin E intake was inversely associated with levels of
      carbonyls (p = 0.05) and olive oil was positively associated with GSH levels (p =
      0.01), in active smokers. Intake of vegetables was related to a decrease of
      malondialdehyde levels (p = 0.04) in former smokers. No statistically significant
      associations were found between remaining dietary antioxidants and serum
      oxidative stress markers. These results provide new data for a potential dietary
      modulation of systemic oxidative stress in COPD patients, particularly in those
      that continue smoking.

PMID- 20815774
TI  - Overcoming platinum resistance in ovarian carcinoma.
AB  - IMPORTANCE OF THE FIELD: Ovarian cancer remains a deadly malignancy because most
      patients develop recurrent disease that is resistant to chemotherapy, including
      platinum. Because response rates for current treatment regimens are relatively
      similar and unfortunately low, no standard chemotherapy for platinum-resistant
      ovarian cancer exists. AREAS COVERED IN THIS REVIEW: A systematic literature
      review of clinical studies published between January 2005 and March 2010 was
      conducted using search engines, PubMed and MEDLINE with the entry keywords
      'ovarian cancer' and 'platinum resistance'. This search revealed 40 clinical
      trials (1793 patients). WHAT THE READER WILL GAIN: Gemcitabine was the most
      common drug used in clinical trials reporting higher response rates, >= +1 SD of
      overall response rate (5 out of 8). Gemcitabine-based combination therapy showed
      an average response rate of 27.2% (95% CI, 22.4-32.0). Combination of gemcitabine
      and pegylated liposomal doxorubicin (PLD) was the most common regimen (n = 3) and
      was associated with possible additive effects in platinum-resistant ovarian
      cancer patients: response rate, gemcitabine alone 6.1%, PLD alone 19.8%, and
      gemcitabine with PLD 28.7% (95% CI, 20.4-37.0), respectively. TAKE HOME MESSAGE:
      Analysis of recent clinical trials showed that gemcitabine-based combination
      chemotherapy was associated with the highest antitumor effects in platinum
      resistant ovarian cancer patients during the study period.

PMID- 20815776
TI  - Palmitate protects hepatocytes from oxidative stress and triacylglyceride
      accumulation by stimulation of nitric oxide synthesis in the presence of high
      glucose and insulin concentration.
AB  - Excessive flux of free fatty acids (FFA) into the liver contributes to liver
      impairment in non-alcoholic fatty liver disease (NAFLD). It remains unclear how
      FFA contribute to impairment of hepatocytes. This study treated hepatocytes with
      linoleic acid and palmitate to investigate the early event triggering FFA
      mediated impairment. It determined cell viability, content of nitrite/nitrate and
      triacylglycerides (TG), inducible nitric oxide synthase (iNOS) protein, oxidation
      of cardiolipin (CL) as well as formation of F(2)-isoprostanes in the presence of
      insulin and glucose. Linoleic acid caused significant decrease in cell viability.
      It is shown that palmitate caused induction of iNOS resulting in increased
      nitrite/nitrate concentration and slight increase in TG content. Linoleic acid
      led to a decrease in nitrite/nitrate concentration parallelled by massive TG
      accumulation in combination with increased oxidation of CL and increased F(2)
      isoprostane levels. It is concluded that nitric oxide (NO) concentration
      regulates FFA-dependent TG accumulation and oxidative stress in rat hepatocytes.

PMID- 20815777
TI  - Peroxynitrite-mediated oxidative modifications of myosin and implications on
      structure and function.
AB  - Abstract The peroxynitrite-induced functional impairment of myosin was studied in
      different reaction conditions, known to alter the oxidative chemistry of
      peroxynitrite, to better understand the molecular mechanisms of this interaction.
      It is shown that peroxynitrite is able to enhance the basal MgATPase activity up
      to 2-fold while inhibiting the actin-stimulated ATPase activity of myosin and
      that the extent of these functional alterations is dependent on the reaction
      medium. The observed changes in the stimulation of the MgATPase activity
      correlate with the extent of carbonyl formation in myosin. The enzyme inhibition
      is more potent in conditions where the efficiency of tyrosine nitration and
      peroxynitrite reactivity towards sulphydryls are lower. Together with the
      observation that reversion of sulphydryl oxidation did not lead to the recovery
      of myosin functional and structural impairments, these results point out to the
      importance of protein carbonylation as a post-translational modification in the
      peroxynitrite-induced myosin functional impairment.

PMID- 20815778
TI  - Beneficial effects of angiotensin II receptor blocker, olmesartan, in limiting
      the cardiotoxic effect of daunorubicin in rats.
AB  - The aim was to evaluate the role of the combination of olmesartan, an angiotensin
      II (Ang II) receptor blocker (ARB), with daunorubicin (DNR) in reducing cardiac
      toxicity in rats. DNR was administered at a dose of 3 mg/kg/day every other day
      for 12 days. Olmesartan was administered orally every day for 12 days. Rats
      treated with DNR alone showed cardiac toxicity as evidenced by worsening cardiac
      function, elevation of malondialdehyde level in heart tissue and decreased in the
      level of total glutathione peroxidase activity; treatment with ARB reversed these
      changes. Furthermore, ARB treatment down-regulated matrix metalloproteinase-2
      expression, myocardial expression of Ang II, attenuated the increased protein
      expressions of p67phox and Nox4 and reduced oxidative stress-induced DNA damage
      evaluated by expression of 8-hydroxydeoxyguanosine. In conclusion, the result
      demonstrated that Ang II and oxidative stress play a key role in anthracycline
      induced cardiotoxicity and that treatment with ARB will be beneficial against DNR
      induced cardiotoxicity.

PMID- 20815779
TI  - Ubiquinol-10 and ubiquinone-10 levels in umbilical cord blood of healthy foetuses
      and the venous blood of their mothers.
AB  - Despite their being good markers of oxidative stress for clinical use, little is
      known about ubiquinol-10 (reduced coenzyme Q10) and ubiquinone-10 (oxidized
      coenzyme Q10) levels in foetuses and their mothers. This study investigates
      oxidative stress in 10 healthy maternal venous, umbilical arterial and venous
      bloods after vaginal delivery by measuring ubiquinol-10 and ubiquinone-10 levels.
      Serum ubiquinol-10 and ubiquinone-10 levels were measured by HPLC with a highly
      sensitive electrochemical detector. Maternal venous ubiquinol-10 and ubiquinone
      10 levels were significantly higher than umbilical arterial and venous levels
      (all p < 0.001). However, the ubiquinone-10/total coenzyme Q10 (CoQ10) ratio,
      which reflects the redox status, was significantly higher in umbilical arterial
      and umbilical venous blood compared to maternal venous blood (all p < 0.001). The
      ubiquinone-10/total CoQ10 ratio was higher in umbilical arterial than in
      umbilical venous blood (p < 0.01). The present study demonstrated that foetuses
      were under higher oxidative stress than their mothers.

PMID- 20815780
TI  - Iron enhances generation of free radicals by Artemisinin causing a caspase
      independent, apoptotic death in Leishmania donovani promastigotes.
AB  - An increasing incidence of unresponsiveness to antimonials in Leishmaniasis has
      led to identification of plant-derived anti-leishmanial compounds like
      Artemisinin. Since iron-mediated generation of free radicals sustains the anti
      malarial activity of Artemisinin, this study investigated whether similar
      mechanisms accounted for its activity in Leishmania promastigotes. Artemisinin
      effectively disrupted the redox potential via an increased generation of free
      radicals along with a decrease in levels of non-protein thiols. Attenuation of
      its IC50 by a free radical scavenger N-acetyl L-cysteine and an iron chelator
      desferoxamine established the pivotal role of free radicals and of the
      potentiating effect of iron. An enhanced Fluo-4 fluorescence reflected
      Artemisinin-induced mobilization of intracellular calcium, which triggered
      apoptosis. However, the absence of any detectable caspase activity indicated that
      the leishmanicidal activity of Artemisinin is mediated by an iron-dependent
      generation of reactive intermediates, terminating in a caspase-independent,
      apoptotic mode of cell death.

PMID- 20815781
TI  - Oxidative stress enhances granulocytic differentiation in HL 60 cells, an acute
      promyelocytic leukemia cell line.
AB  - This paper studied the effects of physiologically available oxidants on HL 60
      differentiation induced by all-trans retinoic acid (ATRA) or dimethyl sulfoxide
      (DMSO). Hydrogen peroxide (15 MUM) and taurine chloramine (200 MUM) induced HL 60
      differentiation, which was detected by CD11b expression and superoxide
      production. Cd11b and p67phox mRNA expression was also augmented by these
      oxidants. In contrast, reducing chemicals, such as dithiothreitol, 2,3-dimercapto
      1-propanol and N-acetylcysteine inhibited CD11b expression. Notably, DMSO
      inhibited methionine sulfoxide reductase activity, induced heme oxygenase-1 (ho
      1) mRNA and enhanced oxidant-induced cell death, which indicated that DMSO
      intensified oxidative stress. After the addition of oxidants, ho-1 expression
      preceded the cd11b expression. Vicinal dithiol-reactive phenylarsine oxide (50
      nM) also increased CD11b expression induced by DMSO or ATRA. These observations
      suggested that oxidative stress enhanced granulocytic differentiation of HL 60
      cells and that leukaemic cell differentiation was affected by cellular redox
      status.

PMID- 20815782
TI  - Effects of cypermethrin on monoamine transporters, xenobiotic metabolizing
      enzymes and lipid peroxidation in the rat nigrostriatal system.
AB  - Long-term exposure to cypermethrin induces the nigrostriatal dopaminergic
      neurodegeneration in adult rats and its pre-exposure in the critical periods of
      brain development enhances the susceptibility during adulthood. Monoamine
      transporters, xenobiotic metabolizing enzymes and oxidative stress play critical
      roles in the nigrostriatal dopaminergic neurodegeneration. The study was
      undertaken to investigate the effects of cypermethrin on DAT, VMAT 2, CYP2E1, GST
      Ya, GST Yc and GSTA4-4 expressions, CYP2E1 and GST activities and lipid
      peroxidation in the nigrostriatal system of adult rats with/without post-natal
      exposure to cypermethrin. Cypermethrin reduced VMAT 2 and increased CYP2E1
      expressions without causing significant change in DAT. Although GSTA4-4 mRNA
      expression and lipid peroxidation were increased, no significant changes were
      observed in GST Ya and GST Yc expressions and total GST activity. The results
      obtained demonstrate that long-term exposure to cypermethrin modulates VMAT 2,
      CYP2E1, GSTA4-4 expressions and lipid peroxidation, which could contribute to the
      nigrostriatal dopaminergic neurodegeneration.

PMID- 20815783
TI  - The mechanism of action of MPTP-induced neuroinflammation and its modulation by
      melatonin in rat astrocytoma cells, C6.
AB  - The 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine (MPTP) induces reactive
      astrogliosis, the cellular manifestation of neuroinflammation, in various models
      of Parkinson's disease (PD), but its mechanism of action on astrocytes is not
      understood. The effect of melatonin on MPTP-induced neuroinflammation in
      astrocytes is also not known. The present study demonstrated that MPTP treatment
      of rat astrocytoma cells, C6 for 24 h significantly increased nitrative and
      oxidative stress and intracellular calcium (Ca2++) level. MPTP also activated
      phosphorylated p38 mitogen activated protein kinase (P-p38 MAPK) and up-regulated
      expressions of inflammatory proteins. Moreover, MPTP modulated mRNA expressions
      of pro-inflammatory cytokine genes via activating nuclear factor kappa-B (NF-kB)
      translocation. Treatment of melatonin with MPTP reversed all these MPTP-induced
      changes. Study with deprenyl demonstrates that MPTP is inducing neuroinflammation
      in astrocytoma cells. The present findings elucidated the molecular mechanism of
      MPTP-induced neuroinflammation and its modulation by melatonin in astrocytoma
      cells (C6).

PMID- 20815784
TI  - S-glutathiolation in life and death decisions of the cell.
AB  - Reversible S-glutathiolation of specific proteins at sensitive cysteines provides
      a powerful mechanism for the dynamic, post-translational regulation of many
      cellular processes, including apoptosis. Critical in ascribing any regulatory
      function to S-glutathiolation is its reversibility, mainly regulated by
      glutaredoxins. Apoptosis is a controlled form of cell death that plays
      fundamental roles during embryonic development, tissue homeostasis and some
      diseases. Much of what happens during the demolition phase of apoptosis is
      orchestrated primarily by caspases, the final executioners of cell death. Recent
      findings support an essential role for S-glutathiolation in apoptosis, often at
      the level of caspases or their inactive precursors, and several studies have
      demonstrated the importance of glutaredoxins in protecting against apoptosis.
      These observations have contributed to recent advances in apoptosis research.
      However, the effective relevance of protein S-glutathiolation and the precise
      molecular targets in apoptotic signalling remain unresolved and a key challenge
      for future research.

PMID- 20815786
TI  - Nitrosylation and nitration of mitochondrial complex I in Parkinson's disease.
AB  - Impairment of the mitochondrial electron transport chain has been suggested to be
      a critical factor in the neuropathogenesis of Parkinson's disease (PD), as
      inhibition of mitochondrial complex I (CI) activity is consistently detected in
      PD patients as well as in mitochondrial toxin models of the disorder. Increased
      levels of various reactive oxygen and nitrogen species appear to contribute to CI
      inhibition and mitochondrial dysfunction in PD. Reactive nitrogen species (RNS)
      such as nitric oxide (NO) and its metabolite peroxynitrite (PN) may inhibit CI
      activity via several different mechanisms including S-nitrosylation, nitration,
      and protein thiol formation. Studies using various cell and animal PD models have
      demonstrated that selective mitochondrial CI inhibition in dopaminergic cells may
      be due to both NO-mediated S-nitrosylation and nitration of CI sub-units.
      Strategies to modulate mitochondrial NO levels will therefore likely be a
      promising approach to enhance mitochondrial function and protect dopaminergic
      neurons against oxidative or nitrosative insult.

PMID- 20815787
TI  - Trypanosoma cruzi dihydrolipoamide dehydrogenase as target of reactive
      metabolites generated by cytochrome c/hydrogen peroxide (or linoleic acid
      hydroperoxide)/phenol systems.
AB  - This study determines that cytochrome c (cyt c) catalyses the oxidation of phenol
      compounds (Phen) in the presence of H2O2 or linoleic acid hydroperoxide (LOOH),
      generating Phen-derived free radicals or other reactive metabolites. These
      products irreversibly inactivated the dihydrolipoamide dehydrogenase from
      Trypanosoma cruzi (T cruzi LADH), depending on: the Phen structure, peroxide
      type, activated cyt c, incubation time and presence of an antioxidant.
      Nordihydroguaiaretic acid (NDGA) and caffeic acid (CAFF) with cyt c/H2O2 or cyt
      c/LOOH were the most effective inhibitors of T cruzi LADH. The comparison of
      inactivation values for T cruzi and mammalian heart enzymes demonstrated a
      greater sensitivity of T cruzi LADH to Phen. GSH, N-acetylcysteine, NAD(P)H,
      ascorbate and trolox, prevented T cruzi LADH inactivation by acetaminophen. The
      role of the Phen as potential trypanocidal systems is discussed.

PMID- 20815785
TI  - Protein oxidative modifications in the ageing brain: consequence for the onset of
      neurodegenerative disease.
AB  - The free radical theory of ageing proposes the accumulation of altered, less
      active and toxic molecules of DNA, RNA, proteins and lipids caused by reactive
      oxygen species and reactive nitrogen species. Neurodegenerative disorders are
      characterized by an abnormal accumulation of oxidatively damaged macromolecules
      inside cells and in the extracellular space. Proteins involved in the formation
      of aggregates are beta-amyloid, tau, alpha-synuclein, parkin, prion proteins and
      proteins containing polyglutamine. These abnormal aggregated proteins influence
      normal cellular metabolism. Additionally, deposition of abnormal proteins induces
      oxidative stress and proteasomal as well as mitochondrial dysfunction that
      ultimately lead to neuronal cell death. This review focuses on the impact of
      oxidative and nitrative stress in the ageing brain and, consequently, on the
      generation of modified proteins, as these post-translational modifications are
      assumed to play an important role in the development of neurodegenerative
      diseases.

PMID- 20815788
TI  - Generation of reactive oxygen species in sperms of rats as an earlier marker for
      evaluating the toxicity of endocrine-disrupting chemicals.
AB  - Bisphenol A (BPA) and diethylstilbestrol (DES) have been reported to cause sperm
      toxicity. To identify an earlier marker of toxicity of environmental substances
      or food additives, this study determined whether the levels of reactive oxygen
      species (ROS) in sperms could serve as indices for the prediction of sperm
      toxicity and quality. Male Wistar rats were given drinking water containing
      various doses of BPA or DES for 8 weeks. Some rats were treated with 0.45% N
      acetyl cysteine (NAC) for 2 days prior to the administration of DES or BPA.
      Administration of BPA or DES to rats for 1 week dose-dependently increased the
      production of ROS, even at doses and time points which had no effect on sperm
      motility. 4-Hydroxy-2-nonenal modified proteins increased in sperms 8 weeks after
      BPA or DES treatment. NAC reversed oxidative stress and prevented the loss of
      sperm function in the DES or BPA-treated group. During observation, changes in
      the sperm motility, sperm count and morphology were not correlated to the
      increase in ROS levels. These results suggest that ROS levels may be used as an
      early indicator of sperm count and quality decreases which result from chronic
      toxicity.

PMID- 20815789
TI  - Nrf2-ARE stress response mechanism: a control point in oxidative stress-mediated
      dysfunctions and chronic inflammatory diseases.
AB  - Nrf2, a redox sensitive transcription factor, plays a pivotal role in redox
      homeostasis during oxidative stress. Nrf2 is sequestered in cytosol by an
      inhibitory protein Keap1 which causes its proteasomal degradation. In response to
      electrophilic and oxidative stress, Nrf2 is activated, translocates to nucleus,
      binds to antioxidant response element (ARE), thus upregulates a battery of
      antioxidant and detoxifying genes. This function of Nrf2 can be significant in
      the treatment of diseases, such as cancer, neurodegenerative, cardiovascular and
      pulmonary complications, where oxidative stress causes Nrf2 derangement. Nrf2
      upregulating potential of phytochemicals has been explored, in facilitating cure
      for various ailments while, in cancer cells, Nrf2 upregulation causes
      chemoresistance. Therefore, Nrf2 emerges as a key regulator in oxidative stress
      mediated diseases and Nrf2 silencing can open avenues in cancer treatment. This
      review summarizes Nrf2-ARE stress response mechanism and its role as a control
      point in oxidative stress-induced cellular dysfunctions including chronic
      inflammatory diseases.

PMID- 20815790
TI  - Increased nitration and diminished activity of copper/zinc superoxide dismutase
      in placentas from diabetic rats.
AB  - Nitration-induced protein damage in the placenta leads to impaired blood flow and
      deficient feto-placental exchange in diabetic pregnancies. This work studied the
      effect of nitric oxide and peroxynitrite on Cu/Zn SOD activity in rat placentas
      and evaluated whether Cu/Zn SOD is nitrated in the placenta from diabetic rats at
      mid-gestation. Protein nitration was evaluated by EIA, Cu/Zn SOD activity by
      inhibition of the epinephrine auto-oxidation, Cu/Zn SOD expression by western
      blot and specific nitration by immunoprecipitation. This study found higher
      levels of protein nitration (p < 0.001), diminished Cu/Zn SOD activity and
      enhanced protein expression (p < 0.01) in placentas from diabetic rats. Placental
      Cu/Zn SOD activity was inhibited by peroxynitrite (p < 0.01). Besides, nitration
      of Cu/Zn SOD was elevated in placentas from diabetic rats (p < 0.01). These
      results show that rat Cu/Zn SOD can be nitrated, a modification that could lead
      to the depressed activity of this enzyme found in placentas from diabetic rats.

PMID- 20815792
TI  - Efficient drug delivery to lung epithelial lining fluid by aerosolization of
      ciprofloxacin incorporated into PEGylated liposomes for treatment of respiratory
      infections.
AB  - PURPOSE: The efficacy of aerosolization of ciprofloxacin (CPFX) incorporated into
      PEGylated liposomes (PEGylated CPFX-liposomes) for the treatment of respiratory
      infections was evaluated. METHOD: PEGylated CPFX-liposomes with 1,2-distearoyl-sn
      glycero-3-phosphoethanolamine-n-[methoxy(polyethylene glycol)-2000] (particle
      size: 100 nm) were prepared, and the drug distribution characteristics in lung
      epithelial lining fluid (ELF) following aerosolization of PEGylated CPFX
      liposomes were examined in rats. Furthermore, the antibacterial effects of
      PEGylated CPFX-liposomes in ELF were evaluated by pharmacokinetic/pharmacodynamic
      analysis. RESULTS: The elimination rate of CPFX from ELF following aerosolization
      of PEGylated CPFX-liposomes was significantly slower than that of CPFX
      incorporated into unmodified liposomes (unmodified CPFX-liposomes; particle size:
      100 nm). According to pharmacokinetic/pharmacodynamic analysis, the PEGylated
      CPFX-liposomes exhibited potent antibacterial effects against pathogenic
      microorganisms in ELF. CONCLUSION: This study shows that PEGylated CPFX-liposomes
      are a useful aerosol-based pulmonary drug delivery system for the treatment of
      respiratory infections.

PMID- 20815791
TI  - Ascorbic acid prevents increased endothelial permeability caused by oxidized low
      density lipoprotein.
AB  - Abstract Mildly oxidized low density lipoprotein (mLDL) acutely increases the
      permeability of the vascular endothelium to molecules that would not otherwise
      cross the barrier. This study has shown that ascorbic acid tightens the
      permeability barrier in the endothelial barrier in cells, so this work tested
      whether it might prevent the increase in endothelial permeability due to mLDL.
      Treatment of EA.hy926 endothelial cells with mLDL decreased intracellular GSH and
      activated the cells to further oxidize the mLDL. mLDL also increased endothelial
      permeability over 2 h to both inulin and ascorbate in cells cultured on semi
      permeable filters. This effect was blocked by microtubule and microfilament
      inhibitors, but not by chelation of intracellular calcium. Intracellular
      ascorbate both prevented and reversed the mLDL-induced increase in endothelial
      permeability, an effect mimicked by other cell-penetrant antioxidants. These
      results suggest a role for endothelial cell ascorbate in ameliorating an
      important facet of endothelial dysfunction caused by mLDL.

PMID- 20815793
TI  - The effect of spray drying on the compaction properties of hypromellose acetate
      succinate.
AB  - BACKGROUND: The aim of this study was to evaluate the compaction behavior of a
      model two-component amorphous spray-dried dispersion system compared with the
      unprocessed excipients, using simulated rotary tablet press production
      conditions. METHOD: In this study, the stabilizing polymer, hypromellose acetate
      succinate (HPMCAS), was solubilized and spray dried with and without sodium
      lauryl sulfate (SLS). The impact of compression force and speed on the tabletting
      process was quantified by means of tablet tensile strength, compaction energy,
      and Heckel analysis. RESULTS: Addition of the surfactant SLS, spray dried or as a
      physical mix, reduced the tablet strength. However, a lesser impact on the
      unprocessed excipients was observed in comparison with the spray-dried
      excipients. In the presence of 1% (w/w) SLS, tablets displayed a tendency to cap
      when compressed at higher speeds, supported by high elastic energy values
      indicating high uniaxial stress upon decompression. In the presence of 3% (w/w)
      SLS, tablets could not be produced at high speeds. Heckel analysis revealed a
      greater strain rate sensitivity of HPMCAS when spray dried in the presence of
      surfactant. Exposure of samples to a range of relative humidities before
      compaction had no effect on tablet strength. CONCLUSION: This study has shown
      that spray drying of HPMCAS in the presence of a surfactant affects the
      compressibility of the material, resulting in decreased tablet strength,
      increased elastic deformation, and capping.

PMID- 20815794
TI  - Enthalpy relaxation studies of two structurally related amorphous drugs and their
      binary dispersions.
AB  - OBJECTIVE: The purpose of the current study was to evaluate the enthalpy
      relaxation behavior of valdecoxib (VLB) and etoricoxib (ETB) and their binary
      dispersions to derive relaxation constants and to understand their molecular
      mobilities. METHODS: Solid dispersions of VLB and ETB were prepared with 1%, 2%,
      5%, 10%, 15%, and 20% (w/w) concentrations of polyvinylpyrrolidone (PVP) in situ
      using differential scanning calorimetry (DSC). Enthalpy relaxation studies were
      carried out with isothermal storage periods of 1, 2, 4, 6, 16, and 24 hours at 40
      degrees C and 0% relative humidity (RH). RESULTS: PVP increased the glass
      transition temperature (T(g)) and decreased the enthalpy relaxation. Significant
      differences between two drugs were observed with respect to their relaxation
      behavior which may be due to differences in intermolecular interactions as
      predicted by Couchman-Karasz equation and molecular mobility. Kohlrausch-Williams
      Watts equation was found to be inadequate in describing complex molecular
      relaxations in binary dispersions. The enthalpy relaxation behavior of VLB and
      ETB was found to be significantly different. PVP stabilized VLB significantly;
      however, its effect on ETB was negligible. The extent of enthalpy relaxation was
      found to correlate with hydrogen bonding tendency of the drug molecules.
      CONCLUSION: The outcome can help in rational designing of amorphous systems with
      optimal performance.

PMID- 20815795
TI  - Role of continuous moisture profile monitoring by inline NIR spectroscopy during
      fluid bed granulation of an Enalapril formulation.
AB  - BACKGROUND: Granulation and tableting are closely related process steps in the
      supply chain of pharmaceutical products. Even today, these steps are still
      optimized independently by trial and error. On the framework of a process
      analytical technology approach, these processes were evaluated in an integrated
      approach. Enalapril maleate is a low-dose drug substance with poor granulating
      and tableting behavior. In order to verify how granulation influences tableting
      properties, different granulation experiments were performed. METHODS:
      Granulation experiments with fast spraying rate and fast drying as well as fast
      spraying rate and slow drying, and also combinations of both were run. The
      obtained granules were then promptly compressed into tablets in a rotary press
      and subjected to hardness testing. The progress of spraying and drying was
      controlled by a continuous near-infrared spectroscopic measuring setup. This
      study confirms that the tablet characteristics. RESULT/CONCLUSION: after
      compression of the granules in comparison to placebo granules are dependent not
      only on the residual moisture content of the granules but also on the moisture
      profiles during the entire fluid bed granulation process.

PMID- 20815796
TI  - Influence of the inlet air temperature in a fluid bed coating process on drug
      release from shellac-coated pellets.
AB  - CONTEXT: Since the introduction of aqueous ammoniacal solutions, shellac regained
      importance for pharmaceutical applications. However, as shellac is a material
      obtained from natural resources, its quality and thus its physicochemical
      properties may vary depending on its origin and the type of refining. OBJECTIVE:
      In this study theophylline pellets were coated with aqueous solutions of three
      different commercially available shellac types. The inlet air temperature of the
      coating process was varied, and its influence on drug release from the coated
      pellet formulations was investigated. Film formation was correlated to the
      physicochemical and mechanical properties of the investigated shellac types.
      RESULTS: Pellets coated at lower temperatures showed distinct cracks in the
      coating film resulting in a loss of the barrier function during dissolution
      testing. These cracks were nonreversible by additional curing. The
      physicochemical and mechanical properties of the investigated shellac types
      varied significantly and could hardly be related to the drug release performance
      of the investigated formulations. CONCLUSION: Obviously, with shellac a minimum
      inlet air temperature must be exceeded to achieve a coherent coating film. This
      temperature was dependent on the investigated shellac type.

PMID- 20815797
TI  - Role of humic acid on oral drug delivery of an antiepileptic drug.
AB  - CONTEXT: Humic acid (HA) is omnipresent in natural organic matter that is a
      macromolecular, negatively charged polyelectrolyte that contains a hydrophobic
      core. It is also present in a significant amount in Shilajit (used frequently in
      traditional medicines), which is used in this study as a source of extraction. HA
      is evaluated for the oral drug delivery of carbamazepine (CBZ). OBJECTIVE: HA is
      used in this study to increase the dissolution, intestinal permeation, and
      pharmacodynamic response of CBZ (bio pharmaceutics classification system (BCS)
      II) by the technique of complexation and other related mechanism reported with
      humic substances. METHODS: Different complexation techniques were explored in
      this study for the entrapment of CBZ, which was authenticated by molecular
      modeling and conformational analysis. These were further characterized using
      differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy
      (FT-IR), and X-ray diffraction (XRD). Solubility analysis and dissolution release
      profile were carried out to access the in vitro parameters. For ex vivo studies,
      rat gut intestinal permeability was done. And finally pharmacodynamic evaluation
      (maximal electroshock method) was carried out for optimized complexes. RESULTS:
      Molecular modeling approach and instrumental analysis (DSC, XRD, and FT-IR)
      confirmed the entrapment of CBZ inside the complexing agent. Increased solubility
      (~1742%), sustained release (~78%), better permeability (~3.5 times), and
      enhanced pharmacodynamic responses conferred the best to 1:2 freeze dried (FD)
      and then 1:2 kneading (KD) complexes compared with pure CBZ. CONCLUSION: Now it
      could be concluded that HA may be tried as a complexing agent for antiepileptic
      drug and other classes of low water-soluble drug.

PMID- 20815798
TI  - [Genetic constitution analysis of idiopathic sudden hearing loss].
AB  - OBJECTIVES: The purpose of this research is to understand the etiology of sudden
      hearing loss due to genetic factors in Turkish people. Determination of these
      genetic factors and better understanding of molecular pathogenesis may guide more
      realistic planning and treatment recommendations. PATIENTS AND METHODS: Forty
      patients (Group 1; 19 males, 21 females; mean age 37.9+/-15.6 years; range 9 to
      76 years) who presented with sudden hearing loss to the Ear, Nose and Throat
      Clinic of Medical Faculty Hospital of Cumhuriyet University between January 2008
      and June 2009, and were diagnosed with sudden hearing loss through history,
      physical examination and review of audiometric findings, and 20 healthy
      volunteers (Group 2; 14 males, 6 females; mean age 31.7+/-4.4 years; range 24 to
      43 years) for the control group were included in this study. All Patients were
      evaluated by the genetic clinic for the GJB2, GJB3, GJB6 and WFS1 gene using
      multiplex ligation-dependent probe amplification (MLPA) method mutation analysis.
      RESULTS: No difference was found in the peripheral blood sample analyses of the
      two groups at WFS1 exon 8 and connexin 26, 30 and 31 gene zones using the MLPA
      method with respect to heterozygous mutation (p=0.291, p>0.05). In four patients
      in group 1 heterozygous mutation was detected at the target gene zone.
      Heterozygous mutation was in the WFS1 exon 8 zone in two patients; and in the
      WFS1 exon 1 zone in other two patients. CONCLUSION: Sudden hearing loss studies
      in the future should include connexin 26, connexin 30 and other gene mutations
      that may affect the function of the gap-junction located in the region of the
      cochlea stria vascularis (stV), basal membrane (BM), spiral limbus (Li) and
      spiral ligament (SL). These studies should be performed on larger series, and
      should include family members of patients with sudden hearing loss.

PMID- 20815799
TI  - The use of the latissimus dorsi myocutaneous flap in the reconstruction of
      complex head and neck defects.
AB  - OBJECTIVES: To compare and contrast the use of the latissimus dorsi myocutaneous
      flap in complex head and neck defects requiring major reconstructive surgery with
      respect to the other reconstruction techniques, and to emphasize the importance
      of this flap as an life and surgeon-saving reconstruction modality. PATIENTS AND
      METHODS: In this study, 20 cases (17 males, 3 females; mean age 58.5 years; range
      48 to 72 years) of major head and neck operations reconstructed with a latissimus
      dorsi myocutaneous flap in Istanbul University, Istanbul Medical Faculty, Ear,
      Nose and Throat Clinic between October 2004 and November 2006 were
      retrospectively examined. The latissimus dorsi myocutaneous flap was preferred as
      a primary reconstructive modality in eight of the cases and a secondary
      reconstructive modality in the remaining 12 cases. The reasons for choosing the
      latissimus dorsi myocutaneous flap as the reconstructive modality were examined
      in this study and compared with other reconstruction techniques. RESULTS: Partial
      flap necrosis was observed in four of the 20 cases. In two of these unsuccessful
      cases, minor intervention was sufficient to achieve functionally satisfactory
      results. However, one case with partial flap necrosis was lost due to the
      uncontrollable primary disease. In the one remaining case who had undergone
      cranioplasty, partial necrosis of the flap developed after the completion of
      radiotherapy in the 4th postoperative month. No total flap necrosis was
      encountered in any of the cases. CONCLUSION: The latissimus dorsi myocutaneous
      flap is a reconstructive modality with a high success rate and should be
      considered among reconstruction alternatives.

PMID- 20815800
TI  - [Ophthalmic complications of paranasal sinus mucoceles].
AB  - OBJECTIVES: This study aimed to describe ophthalmic complications of paranasal
      sinus mucoceles and principles of treatment. PATIENTS AND METHODS: The medical
      records of 25 paranasal sinus mucoceles patients (18 males, 7 females; mean age
      35 years; range 20 to 62 years) that had been treated in two different ear, nose
      and throat clinics between the years January 2004 and June 2009 were evaluated
      retrospectively. Out of 22 patients of who had developed internal mucoceles in
      anterior paranasal sinuses, diplopia was observed in five, proptosis in four and
      partial loss of sight in one. Out of three patients with posterior paranasal
      sinus mucoceles, two developed diplopia and one developed proptosis, with loss of
      sight in all three. Eight patients were treated using osteoplastic flap technique
      and the remaining 17 were treated using endoscopic sinus surgery. RESULTS: In
      only one patient was loss of sight permanent whereas, in all the other patients
      eye complications resolved. CONCLUSION: In mucoceles that involve the posterior
      ethmoid and sphenoid sinuses loss of sight can be observed often because of their
      adjacency to the optic nerves, and loss can be permanent in advanced disease. It
      is possible to obtain good results in most patients treated in time with
      endoscopic sinus surgery and osteoplastic flep techniques.

PMID- 20815801
TI  - [Management of recurrent lower lip carcinomas].
AB  - OBJECTIVES: In this study patients who had locoregional recurrence of lower lip
      carcinomas after therapies such as surgery, electrocoagulation, cryotherapy or
      traditional local therapies are discussed. PATIENTS AND METHODS: The records of
      16 cases (1 female, 15 males; mean age 58 years; range 30 to 83 years) with
      recurrent lower lip carcinoma admitted between March 2002 and September 2007 to
      Dr. Abdurrahman Yurtarslan Oncology Training and Research Hospital, Ear, Nose and
      Throat Department were retrospectively reviewed. RESULTS: Fourteen patients had
      been treated in other institutions, while two had been treated in our center.
      Four of the patients had recurrence in the lip, four patients had recurrence only
      in the neck, and the remaining eight patients had both lip and neck recurrence.
      Ten patients received modified radical or radical neck dissection because of
      their palpable lymphadenopathies, three patients received supraomohyoid neck
      dissection due to non palpable lymphadenopathies, and the remaining three
      patients did not have neck dissection because of co-morbid diseases. Seven
      patients (43%) died in the first postoperative year because of lower lip
      carcinomas and three patients died because of other reasons. Six patients
      survived for the first two years without any evidence of disease. CONCLUSION:
      Patient survival will be affected by the applied treatment. For patients with
      primary lower lip cancers, otolaryngologists experienced in oncology must plan
      surgery rather than local treatments. In case of locoregional recurrence,
      immediate treatment should be planned.

PMID- 20815802
TI  - [Revision surgery for chronic otitis media: evaluation of indications and
      results].
AB  - OBJECTIVES: In patients who underwent primary and revision surgery for chronic
      otitis media, the types of revision surgery, most frequently observed regions of
      cholesteatoma, hearing results and the status of graft membrane were evaluated.
      PATIENTS AND METHODS: Forty-three of 495 patients (21 males, 22 females; mean age
      38.4+/-15.2 years; range 15 to 76 years) with chronic otitis media who underwent
      revision surgery in our clinic between May 2003 and March 2009 were evaluated
      retrospectively. Indications for revision surgery were recurrence of the disease
      in 32 patients (74.4%) and reconstruction of hearing in 11 patients (25.6%).
      Forty patients (93.0%) underwent revision surgery once and three patients (7.0%)
      underwent revision twice. Over an average of 3.2 (range 1 to 6) years follow-up
      after primary and revision surgery, the types of revision surgery, the most
      frequently observed regions of cholesteatoma, hearing results and the status of
      graft membrane were assessed. RESULTS: Recurrence of cholesteatoma in revision
      surgery was seen in 28 patients (65.1%). Out of 27 patients, 23 patients (85.1%)
      showed intact graft membranes and four patients (14.8%) showed perforated graft
      membranes. CONCLUSION: In revision surgery, the first goal is to eliminate the
      disease. The management of chronic otitis media with cholesteatoma is surgery.
      Because of high postoperative recurrence rates, long-term follow-up is necessary.

PMID- 20815803
TI  - [Patterns of cervical metastasis from squamous cell carcinoma of the head and
      neck].
AB  - OBJECTIVES: In this study, the existence, distribution and characteristics of
      cervical lymph nodes metastases in patients with laryngeal, hypopharyngeal and
      intraoral squamous cell cancer were investigated. PATIENTS AND METHODS: A
      retrospective review of the charts of 81 laryngeal, hypopharyngeal and intraoral
      cancer patients (10 females, 71 males; mean age 55.9 years; range 30 and 81
      years) surgically treated and followed up in Haseki Training and Research
      Hospital Ear, Nose and Throat Clinic between January 2004 and October 2007 was
      evaluated. The demographic data of the patients, tumor localization sites,
      surgical techniques, TNM stages and regional neck metastases were evaluated.
      RESULTS: In laryngeal cancer patients, metastatic lymph nodes were found in 36 of
      83 (43%) neck specimens. Patients with intraoral tumors had metastases in six
      (36.4%) of 20 neck specimens. In hypopharynx tumor patients in six of seven
      (85.7%) showed metastasis. CONCLUSION: These results suggest that elective neck
      treatment in patients with head and neck squamous cell cancers, should include
      neck levels I, II, III, IV and V. Upper aerodigestive system squamous cell
      cancers have specific patterns of invasion in cervical region. According to the
      localization of the primary tumor, high risk sites of metastases were detected.
      Selective neck dissections were planned according to these invasion patterns of
      tumors.

PMID- 20815804
TI  - [The healing effects of vitamin E with corticosteroid and vitamin E alone on
      nerve healing in rats with traumatic facial palsy].
AB  - OBJECTIVES: We aimed to document the effects of vitamin E and vitamin E plus
      corticosteroid on nerve healing in rats. MATERIALS AND METHODS: Twenty-four
      Wistar Albino type female rats were used in the study. The rats were divided in
      to three groups, each with eight rats. Group 1 was given methylprednisolone and
      Vitamin E, group 2 was given Vitamin E alone and group 3 was the control group.
      The buccal branch of the facial nerve was found under anesthesia in all rats.
      After nerve identification, the stimulation thresholds were assessed by Xomed
      Trace Nerve Integrity Monitor NIM-2. The buccal branch of each facial nerve in
      group 1 and 2 was traumatized by a vascular clamp for an hour. After trauma the
      stimulus thresholds were identified again. The nerve was not traumatized in group
      3. Group 1 was given 0.1 mg/kg/day vitamin E intramuscular (i.m) and 1 mg/kg/day
      methylprednisolone i.m for one month, group 2 was given 0.1 mg/kg/day vitamin E
      i.m for one month and the control group was given 2 cc 0.09% NaCl subcutaneously
      every other day for one month. At the end of a month the stimulus thresholds were
      measured again and compared statistically. RESULTS: Mean stimulus threshold was
      0.12 mA for all of the groups at the beginning of the experiment. After trauma
      mean stimulus threshold was 0.48 mA for the group 1 and 2. At the end of one
      month stimulus threshold was 0.22 mA for the group 1 and 0.33 mA for the group 2.
      The stimulus threshold in the control group was measured as 0.12 mA. CONCLUSION:
      We concluded that the vitamin E has a positive effect on nerve healing and
      corticosteroid enhances its effect.

PMID- 20815805
TI  - Pulsatile oropharyngeal and neck mass caused by bilateral tortuous internal
      carotid artery: a case report.
AB  - The cervical course of the internal carotid artery is almost straight in contrast
      to the intracranial portions which are highly tortuous. The incidence of
      variations in the cervical course of the internal carotid artery of the
      population is approximately 10-40 percent. In this case report, a 76-year-old
      female patient with a pulsatile mass at the posterior oropharyngeal wall and
      anterior neck was presented. Physical examination revealed a pulsatile anterior
      neck mass, and a pulsatile mass at the right posterior wall of the oropharynx.
      Imaging revealed a bilateral tortuous internal carotid artery and segmental left
      internal carotid arterectomy and distal internal carotid artery - lateral common
      carotid artery anastamosis were performed with no postoperative complications.

PMID- 20815806
TI  - Adenolipoma of the nose: a case report.
AB  - Adenolipoma is a rare benign neoplasm composed of both mature adipose tissue and
      glandular elements. In this article we report a case of 19-year-old woman, who
      had nasal blockage and deformity. On examination, a round, soft, nonpulsatile
      submucosal mass in the cartilagenous vault of the right nasal cavity was found.
      There was also alar rim notching, nostril asymmetry on the right side and septal
      deviation towards the opposite side. Computed tomography revealed a clearly
      demarcated dense mass located at the right submucopericondrial level obstructing
      the nasal passage. An open septorhinoplasty approach was preferred to remove the
      mass and also to correct the deformities caused by the mass. The histopathologic
      examination was reported as an adenolipoma. No recurrence was observed during
      postoperative two year follow-up. To our knowledge, this is the first case report
      of an adenolipoma of the nose in the English literature.

PMID- 20815807
TI  - Ganglioglioma in the nasal cavity: a case report.
AB  - Ganglioglioma is a tumor containing both astrocytic and neuronal components. It
      may occur any where in the central nervous system and spinal cord but is only
      encountered rarely. Nasal glial heterotopia (also known as ''nasal glioma''), is
      a rare developmental abnormality seen in a wide age group. Gangliogliomas may
      also manifest as a nasal glial heterotopia, and neurogenic tumors should be
      considered in the presence of a nasal mass. In this article, we present a case of
      ganglioglioma located in the right-nasal cavity. The mass was excised totally
      through an endoscopic approach. The ganglioglioma developed on a nasal glial
      heterotopia base. To our knowledge, a ganglioglioma arising from the nasal cavity
      has not been described previously in the literature.

PMID- 20815808
TI  - Serum microRNA characterization identifies miR-885-5p as a potential marker for
      detecting liver pathologies.
AB  - Circulating miRNAs (microRNAs) are emerging as promising biomarkers for several
      pathological conditions, and the aim of this study was to investigate the
      feasibility of using serum miRNAs as biomarkers for liver pathologies. Real-time
      qPCR (quantitative PCR)-based TaqMan MicroRNA arrays were first employed to
      profile miRNAs in serum pools from patients with HCC (hepatocellular carcinoma)
      or LC (liver cirrhosis) and from healthy controls. Five miRNAs (i.e. miR-885-5p,
      miR-574-3p, miR-224, miR-215 and miR-146a) that were up-regulated in the HCC and
      LC serum pools were selected and further quantified using real-time qPCR in
      patients with HCC, LC, CHB (chronic hepatitis B) or GC (gastric cancer) and in
      normal controls. The present study revealed that more than 110 miRNA species in
      the serum samples and wide distribution ranges of serum miRNAs were observed. The
      levels of miR-885-5p were significantly higher in sera from patients with HCC, LC
      and CHB than in healthy controls or GC patients. miR-885-5p yielded an AUC [the
      area under the ROC (receiver operating characteristic) curve] of 0.904 [95% CI
      (confidence interval), 0.837-0.951, P<0.0001) with 90.53% sensitivity and 79.17%
      specificity in discriminating liver pathologies from healthy controls, using a
      cut off value of 1.06 (normalized). No correlations between increased miR-885-5p
      and liver function parameters [AFP (alpha-fetoprotein), ALT (alanine
      aminotransferase), AST (aspartate aminotransferase) and GGT (gamma-glutamyl
      transpeptidase)] were observed in patients with liver pathologies. In summary,
      miR-885-5p is significantly elevated in the sera of patients with liver
      pathologies, and our data suggest that serum miRNAs could serve as novel
      complementary biomarkers for the detection and assessment of liver pathologies.

PMID- 20815809
TI  - Magnetic resonance imaging of myocardial injury and ventricular torsion after
      marathon running.
AB  - Recent reports provide indirect evidence of myocardial injury and ventricular
      dysfunction after prolonged exercise. However, existing data is conflicting and
      lacks direct verification of functional myocardial alterations by CMR [cardiac MR
      (magnetic resonance)]. The present study sought to examine structural myocardial
      damage and modification of LV (left ventricular) wall motion by CMR imaging
      directly after a marathon. Analysis of cTnT (cardiac troponin T) and NT-proBNP (N
      terminal pro-brain natriuretic peptide) serum levels, echocardiography [pulsed
      wave and TD (tissue Doppler)] and CMR were performed before and after amateur
      marathon races in 28 healthy males aged 41 +/- 5 years. CMR included LGE (late
      gadolinium enhancement) and myocardial tagging to assess myocardial injury and
      ventricular motion patterns. Echocardiography indicated alterations of diastolic
      filling [decrease in E/A (early transmitral diastolic filling velocity/late
      transmitral diastolic filling velocity) ratio and E' (tissue Doppler early
      transmitral diastolic filling velocity)] postmarathon. All participants had a
      significant increase in NT-proBNP and/or cTnT levels. However, we found no
      evidence of LV LGE. MR tagging demonstrated unaltered radial shortening,
      circumferential and longitudinal strain. Myocardial rotation analysis, however,
      revealed an increase of maximal torsion by 18.3% (13.1 +/- 3.8 to 15.5 +/- 3.6 
      degrees ; P=0.002) and maximal torsion velocity by 35% (6.8 +/- 1.6 to 9.2 +/-
      2.5  degrees .s-1; P<0.001). Apical rotation velocity during diastolic filling
      was increased by 1.23 +/- 0.33  degrees .s-1 after marathon (P<0.001) in a
      multivariate analysis adjusted for heart rate, whereas peak untwist rate showed
      no relevant changes. Although marathon running leads to a transient increase of
      cardiac biomarkers, no detectable myocardial necrosis was observed as evidenced
      by LGE MRI (MR imaging). Endurance exercise induces an augmented systolic
      wringing motion of the myocardium and increased diastolic filling velocities. The
      stress of marathon running seems to be better described as a burden of myocardial
      overstimulation rather than cardiac injury.

PMID- 20815810
TI  - Gender differences in vascular function and insulin sensitivity in young adults.
AB  - To examine influence of insulin resistance and other clinical risk factors for
      the MetS (metabolic syndrome) on vascular structure and function in young adults.
      This cross-sectional study was conducted in a cohort of young adults (mean age 22
      years) and their siblings participating in a longitudinal study of cardiovascular
      risk (n=370). Insulin sensitivity was determined by euglycaemic insulin clamp.
      EDD (endothelium-dependent dilation) was determined by flow-mediated dilation
      using high-resolution ultrasound imaging of the brachial artery. EID (endothelium
      independent dilation) was determined by NTG (nitroglycerine)-mediated dilation.
      The diameter and cIMT (intima-media thickness) of the carotid artery were also
      measured. There was no significant difference between males and females for age
      or body mass index. However, males had significantly higher glucose and
      triacylglycerol (triglyceride) levels, while the females had significantly higher
      HDL-C (high-density lipoprotein-cholesterol) and insulin sensitivity (13.00 +/-
      0.33 compared with 10.71 +/- 0.31 mg.kg-1 of lean body mass.min-1, P<0.0001).
      Although peak EDD was significantly lower (6.28 +/- 0.26 compared with 8.50 +/-
      0.28%, P<0.0001) in males than females, this difference was largely explained by
      adjustment for brachial artery diameter (P=0.15). Peak EID also was significantly
      lower in males than females (20.26 +/- 0.44 compared with 28.64 +/- 0.47%,
      P<0.0001), a difference that remained significantly lower after adjustment for
      brachial artery diameter. Males had a significantly greater cIMT compared with
      females (females 0.420 +/- 0.004 compared with males 0.444 +/- 0.004 mm, P=0.01),
      but when adjusted for carotid diameter, there was no significant difference
      (P=0.163). Although there were gender differences in vascular function and
      structure in the young adult population examined in this study, many of the
      differences were eliminated simply by adjusting for artery diameter. However, the
      lower EID observed in males could not be explained by artery diameter. Future
      studies need to continue to examine influence of gender on EID and other measures
      of vascular function.

PMID- 20815811
TI  - Aberrant methylation of hMLH1 and p16INK4a in Tunisian patients with sporadic
      colorectal adenocarcinoma.
AB  - The methylation of CpG islands in the promoters is associated with loss of
      protein via repression of gene transcription. Several studies have demonstrated
      that tumour suppressor and DNA repair genes are often aberrantly hypermethylated
      in colorectal cancer. The present study was conducted to examine whether the
      methylation profile of p16INK4a and hMLH1 (human mutL homologue 1) promoters was
      associated with clinical features and patients' survival in CRC (colorectal
      carcinoma). Aberrant methylation of p16INK4a and hMLH1 promoters was found in
      47.2 and 53.4% of tumours respectively. For adjacent non-tumoral mucosa, p16INK4a
      was fully unmethylated in 30% of the cases, whereas hMLH1 was predominantly
      unmethylated (76%). Methylation of p16INK4a correlated with gender and tumour
      size (P=0.005 and 0.035 respectively), whereas those of hMLH1 significantly
      correlated with overall survival (P log rank=0.007). Concomitant methylation of
      p16INK4a and hMLH1 was associated with TNM (tumour, lymph node and metastases)
      stage and tumour size (P=0.024 and 0.021 respectively). Our data show that loss
      of hMLH1 expression through aberrant methylation could be used as a marker of
      poor prognosis in CRC.

PMID- 20815812
TI  - Curcumin regulates miR-21 expression and inhibits invasion and metastasis in
      colorectal cancer.
AB  - Curcumin has promising potential in cancer prevention and therapy by interacting
      with proteins and modifying their expression and activity, which includes
      transcription factors, inflammatory cytokines and factors of cell survival,
      proliferation and angiogenesis. miR-21 is overexpressed in many tumours,
      promoting progression and metastasis. In the present study, we examined the
      potential of curcumin to regulate miR-21, tumour growth, invasion and in vivo
      metastasis in colorectal cancer. In Rko and HCT116 cells, we identified two new
      transcriptional start sites of the miR-21 gene and delineated its promoter
      region. PMA stimulation induced miR-21 expression via motifs bound with AP-1
      (activator protein 1) transcription factors. Curcumin treatment reduced miR-21
      promoter activity and expression in a dose-dependent manner by inhibiting AP-1
      binding to the promoter, and induced the expression of the tumour suppressor
      Pdcd4 (programmed cell death protein 4), which is a target of miR-21. Curcumin
      treated Rko and HCT116 cells were arrested in the G2/M phase with increasing
      concentrations. Furthermore, curcumin inhibited tumour growth, invasion and in
      vivo metastasis in the chicken-embryo-metastasis assay [CAM (chorionallantoic
      membrane) assay]. Additionally, curcumin significantly inhibited miR-21
      expression in primary tumours generated in vivo in the CAM assay by Rko and
      HCT116 cells (P<0.00006 and P<0.035 respectively). Taken together, this is the
      first paper to show that curcumin inhibits the transcriptional regulation of miR
      21 via AP-1, suppresses cell proliferation, tumour growth, invasion and in vivo
      metastasis, and stabilizes the expression of the tumour suppressor Pdcd4 in
      colorectal cancer.

PMID- 20815813
TI  - Regulation of the tumour suppressor Fbw7alpha by PKC-dependent phosphorylation
      and cancer-associated mutations.
AB  - Fbw7 (F-box WD40 protein 7) is a major tumour suppressor, which mediates the
      degradation of several potent oncogenes. PKC (protein kinase C) comprises a
      serine/threonine kinase family that can promote transformation when dysregulated.
      In the present study, we investigated the relationship between Fbw7 and PKC.
      Multiple members of the PKC superfamily interact with the substrate-binding
      domain of Fbw7. However, we find no evidence for Fbw7-mediated degradation of
      PKC. Instead, we demonstrate that Fbw7 is a novel substrate for PKC. Two residues
      within the isoform-specific N-terminus of Fbw7alpha are phosphorylated in a PKC
      dependent manner, both in vitro and in mammalian cells (Ser10 and Ser18).
      Mutational analyses reveal that phosphorylation of Fbw7alpha at Ser10 can
      regulate its nuclear localization. Cancer-associated mutations in nearby residues
      (K11R and the addition of a proline residue at position 16) influence Fbw7alpha
      localization in a comparable manner, suggesting that mislocalization of this
      protein may be of pathological significance. Together these results provide
      evidence for both physical and functional interactions between the PKC and Fbw7
      families, and yield insights into the isoform-specific regulation of Fbw7alpha.

PMID- 20815814
TI  - Functional domains of yeast hexokinase 2.
AB  - Hkx2 (hexokinase 2) from Saccharomyces cerevisiae was one of the first metabolic
      enzymes described as a multifunctional protein. Hxk2 has a double subcellular
      localization: it functions as a glycolytic enzyme in the cytoplasm and as a
      regulator of gene transcription of several Mig1-regulated genes in the nucleus.
      To get more insights into the structure-function relationships of the Hxk2
      protein, we followed two different approaches. In the first, we deleted the last
      eight amino acids of Hxk2 and replaced Ser304 with phenylalanine to generate
      Hxk2(wca). Analysis of this mutant demonstrated that these domains play an
      essential role in the catalytic activity of yeast Hxk2, but has no effect on the
      regulatory function of this protein. In the second, we analysed whether amino
      acids from Lys6 to Met15 of Hxk2 (Hxk2(wrf)) are essential for the regulatory
      role of Hxk2 and whether there is an effect on the hexose kinase activity of this
      protein. In the present paper, we report that the Hxk2(wca) mutant protein
      interacts with the Mig1 transcriptional repressor and the Snf1 protein kinase in
      the nucleus at the level of the SUC2-Mig1 repressor complex. We have demonstrated
      that Hxk2(wca) maintained full regulatory function because the glucose-repression
      signalling of the wild-type machinery is maintained. We also report that the
      Hxk2(wrf) mutant allele is incapable of glucose repression signalling because it
      does not interact with Mig1 at the level of the SUC2-Mig1 repressor complex. The
      two mutants, Hxk2(wca) and Hxk2(wrf) retain single functions, as a
      transcriptional factor or as an enzyme with hexose-phosphorylating activity, but
      have lost the original bifunctionality of Hxk2.

PMID- 20815815
TI  - Functional dissection of the N-terminal degron of human thymidylate synthase.
AB  - Human thymidylate synthase (hTS; EC 2.1.1.45) is one of a small group of
      proteasomal substrates whose intracellular degradation occurs in a ubiquitin
      independent manner. Previous studies have shown that proteolytic breakdown of the
      hTS polypeptide is directed by an intrinsically disordered 27-residue domain at
      the N-terminal end of the molecule. This domain, in co-operation with an alpha
      helix spanning amino acids 31-45, functions as a degron, in that it has the
      ability to destabilize a heterologous polypeptide to which it is attached. In the
      present study, we provide evidence indicating that it is the 26S isoform of the
      proteasome that is responsible for intracellular degradation of the hTS
      polypeptide. In addition, we have used targeted in vitro mutagenesis to show that
      an Arg-Arg motif at residues 10-11 is required for proteolysis, an observation
      that was confirmed by functional analysis of the TS N-terminus from other
      mammalian species. The effects of stabilizing mutations on hTS degradation are
      maintained when the enzyme is provided with an alternative means of proteasome
      association; thus such mutations perturb one or more post-docking steps in the
      degradation pathway. Surprisingly, deletion mutants missing large segments of the
      disordered domain still function as proteasomal substrates; however, degradation
      of such mutants occurs by a mechanism that is distinct from that for the wild
      type protein. Taken together, our results provide information on the roles of
      specific subregions within the intrinsically disordered N-terminal domain of hTS
      in regulation of degradation, leading to a deeper understanding of mechanisms
      underlying the ubiquitin-independent proteasomal degradation pathway.

PMID- 20815816
TI  - Peptidoglycan derived from Staphylococcus epidermidis induces Connexin43
      hemichannel activity with consequences on the innate immune response in
      endothelial cells.
AB  - Gram-positive bacterial cell wall components including PGN (peptidoglycan) elicit
      a potent pro-inflammatory response in diverse cell types, including endothelial
      cells, by activating TLR2 (Toll-like receptor 2) signalling. The functional
      integrity of the endothelium is under the influence of a network of gap junction
      intercellular communication channels composed of Cxs (connexins) that also form
      hemichannels, signalling conduits that are implicated in ATP release and
      purinergic signalling. PGN modulates Cx expression in a variety of cell types,
      yet effects in endothelial cells remain unresolved. Using the endothelial cell
      line b.End5, a 6 h challenge with PGN induced IL-6 (interleukin 6), TLR2 and Cx43
      mRNA expression that was associated with enhanced Cx43 protein expression and gap
      junction coupling. Cx43 hemichannel activity, measured by ATP release from the
      cells, was induced following 15 min of exposure to PGN. Inhibition of hemichannel
      activity with carbenoxolone or apyrase prevented induction of IL-6 and TLR2 mRNA
      expression by PGN, but had no effect on Cx43 mRNA expression levels. In contrast,
      knockdown of TLR2 expression had no effect on PGN-induced hemichannel activity,
      but reduced the level of TLR2 and Cx43 mRNA expression following 6 h of PGN
      challenge. PGN also acutely induced hemichannel activity in HeLa cells
      transfected to express Cx43, but had no effect in Cx43-deficient HeLa OHIO cells.
      All ATP responses were blocked with Cx-specific channel blockers. We conclude
      that acute Cx43 hemichannel signalling plays a role in the initiation of early
      innate immune responses in the endothelium.

PMID- 20815817
TI  - Site-specific modification of calmodulin Ca2(+) affinity tunes the skeletal
      muscle ryanodine receptor activation profile.
AB  - The skeletal muscle isoform of the ryanodine receptor Ca2(+)-release channel
      (RyR1) is regulated by Ca2(+) and CaM (calmodulin). CaM shifts the biphasic
      Ca2(+)-dependence of RyR1 activation leftward, effectively increasing channel
      opening at low Ca2(+) and decreasing channel opening at high Ca2(+). The
      conversion of CaM from a RyR1 activator into an inhibitor is due to the binding
      of Ca2(+) to CaM; however, which of CaM's four Ca2(+)-binding sites serves as the
      switch for this conversion is unclear. We engineered a series of mutant CaMs
      designed to individually increase the Ca2(+) affinity of each of CaM's EF-hands
      by increasing the number of acidic residues in Ca2(+)-chelating positions. Domain
      specific Ca2(+) affinities of each CaM variant were determined by equilibrium
      fluorescence titration. Mutations in sites I (T26D) or II (N60D) in CaM's N
      terminal domain had little effect on CaM Ca2(+) affinity and regulation of RyR1.
      However, the site III mutation N97D increased the Ca2(+)-binding affinity of
      CaM's C-terminal domain and caused CaM to inhibit RyR1 at a lower Ca2(+)
      concentration than wild-type CaM. Conversely, the site IV mutation Q135D
      decreased the Ca2(+)-binding affinity of CaM's C-terminal domain and caused CaM
      to inhibit RyR1 at higher Ca2(+) concentrations. These results support the
      hypothesis that Ca2(+) binding to CaM's C-terminal acts as the switch converting
      CaM from a RyR1 activator into a channel inhibitor. These results indicate
      further that targeting CaM's Ca2(+) affinity may be a valid strategy to tune the
      activation profile of CaM-regulated ion channels.

PMID- 20815818
TI  - Resolution of disulfide heterogeneity in Nogo receptor I fusion proteins by
      molecular engineering.
AB  - NgRI (Nogo-66 receptor) is part of a signalling complex that inhibits axon
      regeneration in the central nervous system. Truncated soluble versions of NgRI
      have been used successfully to promote axon regeneration in animal models of
      spinal-cord injury, raising interest in this protein as a potential therapeutic
      target. The LRR (leucine-rich repeat) regions in NgRI are flanked by N- and C
      terminal disulfide-containing 'cap' domains (LRRNT and LRRCT respectively). In
      the present work we show that, although functionally active, the NgRI(310)-Fc
      fusion protein contains mislinked and heterogeneous disulfide patterns in the
      LRRCT domain, and we report the generation of a series of variant molecules
      specifically designed to prevent this heterogeneity. Using these variants we
      explored the effects of modifying the NgRI truncation site or the spacing between
      the NgRI and Fc domains, or replacing cysteines within the NgRI or IgG hinge
      regions. One variant, which incorporates replacements of Cys266 and Cys309 with
      alanine residues, completely eliminated disulfide scrambling while maintaining
      functional in vitro and in vivo efficacy. This modified NgRI-Fc molecule
      represents a significantly improved candidate for further pharmaceutical
      development, and may serve as a useful model for the optimization of other IgG
      fusion proteins made from LRR proteins.

PMID- 20815819
TI  - Glucosinolate-accumulating S-cells in Arabidopsis leaves and flower stalks
      undergo programmed cell death at early stages of differentiation.
AB  - The plant secondary metabolites glucosinolates (GSL) have important functions in
      plant resistance to herbivores and pathogens. We identified all major GSL that
      accumulated in S-cells in Arabidopsis by MALDI-TOF MS, and estimated by LC-MS
      that the total GSL concentration in these cells is >130 mM. The precise locations
      of the S-cells outside phloem bundles in rosette and cauline leaves and in flower
      stalks were visualised using sulphur mapping by cryo-SEM/energy-dispersive X-ray
      analysis. S-cells contain up to 40% of the total sulphur in flower stalk tissues.
      S-cells in emerging flower stalks and developing leaf tissues show typical signs
      of programmed cell death (PCD) or apoptosis, such as chromatin condensation in
      the nucleus and blebbing of the membranes. TUNEL staining for DNA double-strand
      breaks confirmed the occurrence of PCD in S-cells in post-meristematic tissues in
      the flower stalk as well as in the leaf. Our results indicate that S-cells in
      post-meristematic tissues show an extreme degree of metabolic specialisation in
      addition to PCD. Accumulation and maintenance of a high concentration of GSL in
      these cells are accompanied by degradation of a number of cell organelles. The
      substantial changes in cell composition during S-cell differentiation indicate
      the importance of this particular GSL-based phloem defence system. The specific
      anatomy of the S-cells and the ability to accumulate specialised secondary
      metabolites is similar to that of the non-articulated laticifer cells in latex
      plants, suggesting a common evolutionary origin.

PMID- 20815820
TI  - Tn10/IS10 transposition is downregulated at the level of transposase expression
      by the RNA-binding protein Hfq.
AB  - We show in this work that disruption of the hfq gene in Escherichia coli causes a
      large increase in IS10 transposition when IS10 is present on a multi-copy
      plasmid. Hfq is an RNA-binding protein that regulates the expression of a large
      number of genes at the post-transcriptional level by promoting the pairing of
      mRNAs with partially complementary short RNAs. As the translation of IS10
      transposase mRNA (RNA-IN) is inhibited by an IS10-encoded anti-sense RNA (RNA
      OUT), it seemed likely that Hfq would negatively regulate Tn10/IS10 transposition
      by promoting anti-sense inhibition of RNA-IN translation. Consistent with this,
      we show that Hfq promotes pairing of RNA-IN and RNA-OUT in vitro and
      downregulates RNA-IN expression in vivo. However, we also show that Hfq
      negatively regulates Tn10 transposition when no functional anti-sense RNA is
      produced. Taken together, the results suggest that Hfq acts at two distinct steps
      to inhibit Tn10/IS10 transposition. This is the first example of Hfq regulating a
      bacterial transposition reaction.

PMID- 20815821
TI  - Mapping the pinhole formation pathway of S21.
AB  - Phage holins are small, lethal membrane proteins of two general types: canonical
      holins, like lambda S105, which oligomerizes and forms large membrane holes of
      unprecedented size; and pinholins, like S(21) 68 of lambdoid phage 21, which
      forms homo-heptameric channels, or pinholes, with a lumen of <2 nm. Pinholes
      depolarize the membrane, leading to activation of secreted endolysins and murein
      degradation. S(21) 68 has two transmembrane domains, TMD1 and TMD2. TMD2 alone
      lines the pinhole, making heterotypic interactions involving two surfaces, A and
      B. Mutational analysis on S(21) 68 suggested that S(21) 68 initially forms
      inactive dimer, with TMD1 inhibiting TMD2 both in cis and trans. When TMD1 exits
      the membrane to the periplasm, it liberates TMD2 to participate in the pathway to
      pinhole formation. In this study, further mutational analysis suggests a refined
      pinhole formation pathway, with the existence of at least two intermediate
      states. We propose that the pathway begins in the activated dimer state, with a
      homotypic TMD2 interface involving the A surface. Evidence is presented for a
      further oligomeric state involving a heterotypic A:B interaction. Moreover, the
      data suggest that a glycine-zipper motif present in the A interface of TMD2 is
      involved in every stage downstream of the inactive dimer.

PMID- 20815823
TI  - Vibrio fischeri flavohaemoglobin protects against nitric oxide during initiation
      of the squid-Vibrio symbiosis.
AB  - Nitric oxide (NO) is implicated in a wide range of biological processes,
      including innate immunity against pathogens, signal transduction and protection
      against oxidative stress. However, its possible roles in beneficial host-microbe
      associations are less well recognized. During the early stages of the squid
      vibrio symbiosis, the bacterial symbiont Vibrio fischeri encounters host-derived
      NO, which has been hypothesized to serve as a specificity determinant. We
      demonstrate here that the flavohaemoglobin, Hmp, of V. fischeri protects against
      NO, both in culture and during colonization of the squid host. Transcriptional
      analyses indicate that hmp expression is highly responsive to NO, principally
      through the repressor, NsrR. Hmp protects V. fischeri from NO inhibition of
      aerobic respiration, and removes NO under both oxic and anoxic conditions. A
      Deltahmp mutant of V. fischeri initiates squid colonization less effectively than
      wild type, but is rescued by the presence of an NO synthase inhibitor. The hmp
      promoter is activated during the initial stage of colonization, during which the
      Deltahmp strain fails to form normal-sized aggregates of colonizing cells. Taken
      together, these results suggest that the sensing of host-derived NO by NsrR, and
      the subsequent removal of NO by Hmp, influence aggregate size and, thereby, V.
      fischeri colonization efficiency.

PMID- 20815822
TI  - Identification and function of the RNA chaperone Hfq in the Lyme disease
      spirochete Borrelia burgdorferi.
AB  - Hfq is a global regulatory RNA-binding protein. We have identified and
      characterized an atypical Hfq required for gene regulation and infectivity in the
      Lyme disease spirochete Borrelia burgdorferi. Sequence analyses of the putative
      B. burgdorferi Hfq protein revealed only a modest level of similarity with the
      Hfq from Escherichia coli, although a few key residues are retained and the
      predicted tertiary structure is similar. Several lines of evidence suggest that
      the B. burgdorferi bb0268 gene encodes a functional Hfq homologue. First, the
      hfq(Bb) gene (bb0268) restores the efficient translation of an rpoS::lacZ fusion
      in an E. coli hfq null mutant. Second, the Hfq from B. burgdorferi binds to the
      small RNA DsrA(Bb) and the rpoS mRNA. Third, a B. burgdorferi hfq null mutant was
      generated and has a pleiotropic phenotype that includes increased cell length and
      decreased growth rate, as found in hfq mutants in other bacteria. The hfq(Bb)
      mutant phenotype is complemented in trans with the hfq gene from either B.
      burgdorferi or, surprisingly, E. coli. This is the first example of a
      heterologous bacterial gene complementing a B. burgdorferi mutant. The
      alternative sigma factor RpoS and the outer membrane lipoprotein OspC, which are
      induced by increased temperature and required for mammalian infection, are not
      upregulated in the hfq mutant. Consequently, the hfq mutant is not infectious by
      needle inoculation in the murine model. These data suggest that Hfq plays a key
      role in the regulation of pathogenicity factors in B. burgdorferi and we
      hypothesize that the spirochete has a complex Hfq-dependent sRNA network.

PMID- 20815824
TI  - C-terminal amino acid residues of the trimeric autotransporter adhesin YadA of
      Yersinia enterocolitica are decisive for its recognition and assembly by BamA.
AB  - The Bam complex is a highly conserved multiprotein machine essential for the
      assembly of beta-barrel outer membrane proteins. It is composed of the essential
      outer membrane protein BamA and four outer membrane associated lipoproteins BamB
      E. The Yersinia enterocolitica Adhesin A (YadA) is the prototype of trimeric
      auotransporter adhesins (TAAs), consisting of a head, stalk and a beta-barrel
      membrane anchor. To investigate the role of BamA in biogenesis of TAAs, we
      expressed YadA in a BamA-depleted strain of Escherichia coli, which resulted in
      degradation of YadA. Yeast-two-hybrid experiments and immunofluorescence studies
      revealed that BamA and YadA interact directly and colocalize. As BamA recognizes
      the C-terminus of OMPs, we exchanged the nine most C-terminal amino acids of
      YadA. Substitution of the amino acids in position 1, 3 or 5 from the C-terminus
      with glycine resulted in DegP-dependent degradation of YadA. Despite degradation
      all YadA proteins assembled in the outer membrane. In summary we demonstrate that
      (i) BamA is essential for biogenesis of the TAA YadA, (ii) BamA interacts
      directly with YadA, (iii) the C-terminal amino acid motif of YadA is important
      for the BamA-dependent assembly and differs slightly compared with other OMPs,
      and (iv) BamA and YadA colocalize.

PMID- 20815826
TI  - Vitamin B6 biosynthesis is essential for survival and virulence of Mycobacterium
      tuberculosis.
AB  - With 500000 cases of multidrug-resistant tuberculosis there is an urgent need for
      attractive targets to enable the discovery of novel antimycobacterials. The
      biosynthesis of essential cofactors is of particular interest as these pathways
      are absent in man and their inhibition is expected to affect the metabolism of
      Mycobacterium tuberculosis at multiple sites. Our data demonstrate that the
      pathogen synthesizes pyridoxal 5-phosphate (PLP), the bioactive form of vitamin
      B6, by a heteromeric PLP synthase composed of Pdx1 (Rv2606c) and Pdx2 (Rv2604c).
      Disruption of the pdx1 gene generated a strictly B6 auxotrophic M. tuberculosis
      mutant, Deltapdx1. Removal of the cofactor during exponential growth or
      stationary phase demonstrated the essentiality of vitamin B6 biosynthesis for
      growth and survival of the pathogen in culture. In a tuberculosis dormancy model
      based on gradual oxygen depletion, de novo biosynthesis of PLP was required for
      regrowth of the bacillus after direct oxygen exposure. The Deltapdx1 mutant
      showed a severe growth defect in immunocompetent mice: bacilli applied
      intranasally failed to persist in host tissues and were quickly cleared. We
      conclude that vitamin B6 biosynthesis is required for survival of M. tuberculosis
      in vivo and thus might represent a candidate pathway for the development of new
      antitubercular agents.

PMID- 20815827
TI  - Post-translational control of Bacillus subtilis biofilm formation mediated by
      tyrosine phosphorylation.
AB  - A biofilm is a complex community of cells enveloped in a self-produced polymeric
      matrix. Entry into a biofilm is exquisitely controlled at the level of
      transcription and in the Gram-positive organism Bacillus subtilis it requires the
      concerted efforts of three major transcription factors. Here, we demonstrate that
      in addition to transcriptional control, B. subtilis utilizes post-translational
      modifications to control biofilm formation; specifically through phosphorylation
      of tyrosine residues. Through our work we have assigned novel roles during
      biofilm formation to two proteins; the protein tyrosine kinase PtkA and the
      protein tyrosine phosphatase PtpZ. Furthermore by introducing amino acid point
      mutations within the catalytic domains of PtkA and PtpZ we have identified that
      the kinase and phosphatase activities, respectively, are essential for function.
      PtkA contains a conserved C-terminal tyrosine cluster that is the site of
      autophosphorylation; however, our in vivo analysis demonstrates that this domain
      is not required during biofilm formation. With the aim of identifying the
      target(s) of PtkA controlled during biofilm formation we used a systematic
      mutagenesis approach but, despite extensive efforts, it remained elusive. Our
      findings highlight the complexity of biofilm development by revealing an
      additional level of regulation in the form of protein tyrosine phosphorylation.

PMID- 20815825
TI  - High-order oligomerization is required for the function of the H-NS family member
      MvaT in Pseudomonas aeruginosa.
AB  - H-NS is an abundant DNA-binding protein that has been implicated in the silencing
      of foreign DNA in several different bacteria. The ability of H-NS dimers to form
      higher-order oligomers is thought to aid the polymerization of the protein across
      AT-rich stretches of DNA and facilitate gene silencing. Although the
      oligomerization of H-NS from enteric bacteria has been the subject of intense
      investigation, little is known regarding the oligomerization of H-NS family
      members from bacteria outside of the enterobacteriaceae, many of which share
      little sequence similarity with their enteric counterparts. Here we show that
      MvaT, a member of the H-NS family of proteins from Pseudomonas aeruginosa, can
      form both dimers and higher-order oligomers, and we identify a region within MvaT
      that mediates higher-order oligomer formation. Using genetic assays we identify
      mutants of MvaT that are defective for higher-order oligomer formation. We
      present evidence that these mutants are functionally impaired and exhibit DNA
      binding defects because of their inability to form higher-order oligomers. Our
      findings support a model in which the ability of MvaT to bind efficiently to the
      DNA depends upon protein-protein interactions between MvaT dimers and suggest
      that the ability to form higher-order oligomers is a conserved and essential
      feature of H-NS family members.

PMID- 20815828
TI  - A M23B family metallopeptidase of Helicobacter pylori required for cell shape,
      pole formation and virulence.
AB  - The molecular basis of the regulation of specific shapes and their role for the
      bacterial fitness remain largely unknown. We focused in this study on the Gram
      negative and spiral-shaped Helicobacter pylori. To colonize its unique niche, H.
      pylori needs to reach quickly the human gastric mucosa, by swimming to and
      through the mucus layer. For that reason, the specific shape of H. pylori is
      predicted to be necessary for optimal motility in vivo, and consequently for its
      colonization ability. Here, we describe the involvement of a PG-modifying enzyme,
      HdpA (HP0506), in the mouse colonization ability of this bacterium, by regulating
      its shape. Indeed, the inactivation of the hp0506 gene led to a stocky and
      branched phenotype, affecting H. pylori colonization capacity despite a normal
      motility phenotype in vitro. In contrast, the overexpression of the hp0506 gene
      induced the transformation of H. pylori from rod to dividing cocci shaped
      bacteria. Furthermore, we demonstrated by PG analysis and enzymology, that HdpA
      carried both d,d-carboxypeptidase and d,d-endopeptidase activities. Thus, HdpA is
      the first enzyme belonging to the M23-peptidase family able to perform the d,d
      carboxypeptidation and regulate cell shape.

PMID- 20815829
TI  - Duloxetine hepatotoxicity: a case-series from the drug-induced liver injury
      network.
AB  - BACKGROUND: Case reports suggest that duloxetine hepatotoxicity may arise, but
      risk factors, presenting features and clinical course are not well-described.
      AIM: To describe the presenting features and outcomes of seven well-characterized
      patients with suspected duloxetine hepatotoxicity. METHODS: Patients enrolled in
      the Drug-Induced Liver Injury Network Prospective Study underwent an extensive
      laboratory and clinical evaluation to exclude competing aetiologies of liver
      injury as well as a standardized assessment for causality and disease severity.
      RESULTS: Between 1/2006 and 9/2009, six of the seven cases of DILI attributed to
      duloxetine were assessed as definite or very likely. Median patient age was 49
      years, six (86%) were women and the median latency from drug initiation to DILI
      onset was 50 days. Six patients developed jaundice and the median peak alanine
      aminotransferase in the five patients with acute hepatocellular injury was 1633
      IU/L. Ascites developed in one patient and acute renal dysfunction in two others
      (29%). All patients recovered without liver transplantation even though three had
      pre-existing chronic liver disease. Liver histology in four cases demonstrated
      varying patterns of liver injury. CONCLUSIONS: Duloxetine hepatotoxicity
      developed within 2 months of drug intake and led to clinically significant liver
      injury. A spectrum of laboratory, histological and extra-hepatic features were
      noted at presentation.

PMID- 20815830
TI  - Letters to the Editors: Bowel preparation: which meta-analysis is right? Like the
      cleansing methods, they are all still imperfect.

PMID- 20815832
TI  - Letters to the Editors: Potential pitfalls on the validation of liver stiffness
      measurement by Fibroscan with histological staging in chronic hepatitis B.

PMID- 20815833
TI  - Review article: understanding adherence to medication in ulcerative colitis -
      innovative thinking and evolving concepts.
AB  - BACKGROUND: Non-adherence to medication is an important challenge in the
      treatment of ulcerative colitis (UC). Epidemiological studies have demonstrated
      that non-adherence affects 40-60% of UC patients, and has a substantial impact on
      the course of the disease. In one study, non-adherence was associated with a five
      fold increase in the risk of relapse. AIM: We review factors contributing to non
      adherence to UC therapy, and emerging concepts in addressing the problem.
      METHODS: A search of the published literature on adherence to medication,
      combined with the authors' knowledge of the field. RESULTS: Adherence is a
      complex, multifactorial issue, with factors varying between patients and changing
      over time. Identifying patients at risk of non-adherence is a key first step in
      targeting interventions to improve adherence. However, investigations of single
      factors that affect adherence have provided conflicting evidence. Evaluating
      physical and perceptual barriers to adherence, and acknowledging the role of
      patients' beliefs and concerns regarding treatment provide valuable insights into
      the causes of non-adherence. This allows development of targeted interventions to
      improve adherence to UC therapy. Clinical tools to identify patients at risk of
      non-adherence are being developed to facilitate this approach. CONCLUSIONS: To
      help patients adhere better to maintenance therapy for UC, it is vital to
      consider patients' beliefs and concerns, and to evaluate and address both
      physical and perceptual barriers to adherence.

PMID- 20815837
TI  - Raising the age pension eligibility age and its (dis)contents.

PMID- 20815838
TI  - Increasing the age of eligibility for receipt of aged pension in Australia:
      Potential impact on older people.

PMID- 20815839
TI  - Minimising harm to older Victorians from heatwaves: A qualitative study of the
      role of community-based health profession and carer organisations.
AB  - AIM: To investigate the role of community-based health profession and carer
      organisations in Victoria in minimising harm to older people from heatwaves.
      METHODS: A qualitative study based on semistructured interviews was conducted in
      Victoria, Australia. Twelve people were interviewed, representing four
      professional groups that support the health of older Victorians who reside at
      home. RESULTS: None of the health profession and carer organisations studied had
      formalised heatwave strategies; however, their staff conduct a range of
      activities before and during heatwaves that may reduce harm to older clients.
      Interviewees discussed roles their organisations could play in a heatwave
      response plan, including coordination, identification of high-risk individuals
      and education. All saw a need for extra resources and training if responses to
      heatwaves were required more frequently. CONCLUSION: It may be feasible to
      utilise the existing services and infrastructure of community-based health
      profession and carer organisations operating in Victoria within a State-wide
      Heatwave Response plan; however, this will require extra resources, training and
      coordination.

PMID- 20815840
TI  - Modelling the impact of modifying lifestyle risk factors on dementia prevalence
      in Australian population aged 45 years and over, 2006-2051.
AB  - AIM: To model impact of modifiable risk behaviour on dementia prevalence among
      the Australian population aged 45 years and over. METHODS: A group-based computer
      model was constructed to estimate the impact of modifying risk behaviour on
      dementia prevalence. RESULTS: Based on population ageing, the number of people
      aged 45 years and over living with dementia is expected to triple from 187 000 in
      2006 to 650 000 by 2051. A drop in proportion ever smokers by 5% every 5 years
      would lower population with dementia by 2% in 2051. If obesity rate drops by 5%,
      dementia prevalence would be lower by 6%. A decline in physical inactivity rate
      by 5% would reduce dementia by 11%. Persistence of the growing trend in obesity
      and physical inactivity would result in a larger than expected dementia epidemic.
      CONCLUSION: Improving the risk behaviours has potential to make a substantial
      reduction in the number of people with dementia.

PMID- 20815841
TI  - Age differences in fall-related injury hospitalisations and trauma presentations.
AB  - AIM: To examine fall-related hospitalised morbidity in New South Wales (NSW) and
      to describe the pattern of fall-related major trauma presentations at a Level 1
      Trauma Centre in NSW for younger and older fallers. METHODS: Fall-related
      injuries were identified in the NSW Admitted Patients Data Collection during 1
      July 1999-30 June 2008 and the trauma registry of the NSW St George Public
      Hospital during 1 January 2006-6 December 2008. RESULTS: There were 434 138
      hospitalisations and 862 fall-related trauma presentations. Older fallers had a
      higher incidence of hospitalisation, being more likely to fall on the same level
      during general activities at home, injuring their hip or thigh. Older fallers
      were also more likely to have an Injury Severity Score > 9, undergo physiotherapy
      and stay in hospital for >1 day than younger fallers. CONCLUSION: Falls,
      particularly for older individuals, are an important cause of serious injury,
      representing a considerable burden in terms of hospitalised morbidity.

PMID- 20815842
TI  - The Eden model: Innovation in Australian aged care?
AB  - AIM: The Eden model of care is part of discourse associated with innovation in
      aged care. There is, however, limited rigorous research to identify its essential
      claims. This paper examines the implementation of the Eden model in one
      integrated health service in rural Australia. METHODS: Data are derived from a
      small qualitative study that explored the views of staff. RESULTS: Findings
      highlight that while the discourse of the Eden model is accessible to all staff
      within aged care and is linked to person-centred care, there is tension with this
      practice of aged care within the Australian context. CONCLUSION: It is
      appropriate to ask if this form of care is innovative; what constitutes
      innovation and the importance of accounting for wider contextual factors. There
      is a need to build on this exploratory study with dialogue and research of not
      only the Eden model, but innovation in aged care within Australia.

PMID- 20815843
TI  - Australian baby boomers talk about the global financial crisis.
AB  - AIM: The aim of this qualitative study was to explore baby boomers' views and
      plans in the early days of the global financial crisis (GFC) in 2008. METHODS:
      Informants from National Seniors Australia were interviewed in 15 focus groups
      conducted nationally. Transcripts were analysed by themes from semi-structured
      questions. RESULTS: The GFC was found to shake the confidence and plans of
      boomers. Many workers decided to delay retirement and save longer following
      losses in superannuation. Those retired on market-linked superannuation felt
      forced to reduce expenses and restrain lifestyles. Those on full pensions were
      relatively unaffected. CONCLUSION: The GFC called into question boomers'
      expectations for retirement. While financial markets are showing signs of
      recovery, the GFC had precipitated a decision to work longer and to draw
      conservatively on retirement savings that may take many years to recover. The
      volatility of financial and employment markets underscores the value of the Age
      pension.

PMID- 20815844
TI  - Hoarding in older people: The role of the Aged Care Assessment Service.

PMID- 20815845
TI  - Teaching geriatric medicine in Vietnam: Introduction of an interactive learning
      module for medical students.

PMID- 20815846
TI  - Australian and New Zealand Society for Geriatric Medicine position statement
      driving and dementia.

PMID- 20815851
TI  - How should single-access or natural orifice cholecystectomy be introduced?

PMID- 20815852
TI  - Ischaemic preconditioning of the graft in adult living related right lobe liver
      transplantation: impact on ischaemia-reperfusion injury and clinical relevance.
AB  - BACKGROUND: Ischaemic preconditioning (IPC) of the right liver graft in the donor
      has not been studied in adult-to-adult living related liver transplantation
      (LRLT). OBJECTIVE: To assess the IPC effect of the graft on ischaemia reperfusion
      injury in the recipient and compare recipient and donor outcomes with and without
      preconditioned grafts. PATIENTS AND METHODS: Alternate patients were transplanted
      with right lobe grafts that were (n = 22; Group (Precond)) or were not (n = 22;
      Group (Control)) subjected to IPC in the living donor. Liver ischaemia
      reperfusion injury, liver/kidney function, morbidity/mortality rates and outcomes
      were compared. Univariate and multivariate analyses were performed to identify
      factors predictive of the aspartate aminotransferase (AST) peak and minimum
      prothrombin time. RESULTS: Both groups had similar length of hospital stay,
      morbidity/mortality, primary non-function and acute rejection rates. Post
      operative AST (P = 0.8) and alanine aminotransferase (ALT) peaks (P = 0.6) were
      similar in both groups (307 +/- 189 and 437 +/- 302 vs. 290 +/- 146 and 496 +/-
      343, respectively). In univariate analysis, only pre-operative AST and warm
      ischemia time (WIT) were significantly associated with post-operative AST peak
      (in recipients). In multivariate analysis, the graft/recipient weight ratio (P =
      0.003) and pre-operative bilirubin concentration (P = 0.004) were significantly
      predictive of minimum prothrombin time post-transplantation. CONCLUSIONS: Graft
      IPC in the living related donor is not associated with any benefit for the
      recipient or the donor and its clinical value remains uncertain.

PMID- 20815853
TI  - Invasive intraductal papillary mucinous neoplasm: predictors of survival and role
      of adjuvant therapy.
AB  - BACKGROUND: Adjuvant treatment for pancreatic adenocarcinoma has been shown to
      improve survival. An increasingly recognized 'subtype' of pancreatic
      adenocarcinoma is invasive intraductal papillary mucinous neoplasm (IPMN). It is
      unclear whether adjuvant treatment for invasive IPMN improves survival. This
      study aimed to determine the impact of adjuvant treatment in invasive IPMN.
      METHODS: We conducted a retrospective analysis of merged clinical databases
      including 412 patients undergoing resection for IPMN at two academic institutions
      between 1989 and 2006. RESULTS: Of 412 patients with IPMN who underwent
      pancreatectomy, 98 had invasive carcinoma. Median survival in invasive IPMN was
      32 months. Adjuvant treatment did not affect median survival in node-positive or
      node-negative invasive IPMN. Biopsy-proven recurrence of invasive IPMN occurred
      in 45 patients (46%). The median disease-free interval from resection to
      recurrence was 27 months. Treatment of recurrences with chemotherapy or radiation
      therapy was not associated with a difference in survival; however, a subgroup of
      patients with recurrence in the remnant pancreas who underwent re-resection
      appeared to have more favourable outcomes. CONCLUSIONS: An invasive component
      measuring >2 cm and lymph node involvement are associated with poorer prognosis.
      Adjuvant therapy in invasive IPMN appears to confer no survival benefit. In
      selected patients with recurrence of invasive IPMN in the remnant pancreas, re
      resection should be considered.

PMID- 20815854
TI  - Model for end-stage liver disease-based allocation system for liver
      transplantation in Argentina: does it work outside the United States?
AB  - BACKGROUND: In July 2005, Argentina was the first country after the United States
      to adopt the MELD system. The purpose of the present study was to analyse the
      impact of this new system on the adult liver waiting list (WL). METHODS: Between
      2005 and 2009, 1773 adult patients were listed for liver transplantation: 150
      emergencies and 1623 electives. Elective patients were categorized using the MELD
      system. A prospective database was used to analyse mortality and probability to
      be transplanted (PTBT) on the WL. RESULTS: The waiting time increased inversely
      with the MELD score and PTBT positively correlated with MELD score. With scores
      >/= 18 the PTBT remained over 50%. However, the largest MELD subgroup with <10
      points (n = 433) had the lower PTBT (3%). In contrast, patients with T(2)
      hepatocellular carcinoma benefited excessively with the highest PTBT (84.2%) and
      the lowest mortality rate (5.4%). The WL mortality increased after MELD adoption
      (10% vs. 14.8% vs. P < 0.01). Patients with <10 MELD points had >fourfold
      probability of dying on the WL than PTBT (14.3% vs. 3%; P < 0.0001). CONCLUSIONS:
      After MELD implementation, WL mortality increased and most patients who died had
      a low MELD score. A comprehensive revision of the MELD system must be performed
      to include cultural and socio-economical variables that could affect each country
      individually.

PMID- 20815855
TI  - Peri-operative blood transfusion and operative time are quality indicators for
      pancreatoduodenectomy.
AB  - BACKGROUND: Minimization of blood loss during pancreatoduodenectomy requires
      careful surgical technique and specific preventative measures. Therefore, red
      blood cell (RBC) transfusions and operative time are potential surgical quality
      indicators. The aim of the present study was to compare peri-operative RBC
      transfusion and operative time with 30-day morbidity/mortality after
      pancreatoduodenectomy. METHODS: All pancreatoduodenectomies (2005 to 2008) were
      identified using the American College of Surgeons-National Surgical Quality
      Improvement Program (ACS-NSQIP). RBC transfusions and operative time were
      correlated with 30-day morbidity/mortality. RESULTS: Pancreatoduodenectomy was
      completed in 4817 patients. RBC transfusions were given to 1559 (32%) patients (1
      35 units). Overall morbidity and mortality rates were 37% and 3.0%, respectively.
      Overall 30-day morbidity increased in a stepwise manner with the number of RBC
      transfusions (R = 0.69, P < 0.01). Although RBC transfusions and operative times
      were not statistically linked (P = 0.87), longer operative times were linearly
      associated with increased 30-day morbidity (R = 0.79, P < 0.001) and mortality (R
      = 0.65, P < 0.01). Patients who were not transfused also displayed less morbidity
      (33%) and mortality (1.9%) (P < 0.05). DISCUSSION: Peri-operative RBC transfusion
      after pancreatoduodenectomy is linearly associated with 30-day morbidity. Longer
      operative time also correlates with increased morbidity and mortality. Therefore,
      blood transfusions and prolonged operative time should be considered quality
      indicators for pancreatoduodenectomy.

PMID- 20815856
TI  - Drain data to predict clinically relevant pancreatic fistula.
AB  - BACKGROUND: Post-operative pancreatic fistula (POPF) is a common and potentially
      devastating complication of pancreas resection. Management of this complication
      is important to the pancreas surgeon. OBJECTIVE: The aim of the present study was
      to evaluate whether drain data accurately predicts clinically significant POPF.
      METHODS: A prospectively maintained database with daily drain amylase
      concentrations and output volumes from 177 consecutive pancreatic resections was
      analysed. Drain data, demographic and operative data were correlated with POPF
      (ISGPF Grade: A--clinically silent, B--clinically evident, C--severe) to
      determine predictive factors. RESULTS: Twenty-six (46.4%) out of 56 patients who
      underwent distal pancreatectomy and 52 (43.0%) out of 121 patients who underwent
      a Whipple procedure developed a POPF (Grade A-C). POPFs were classified as A (24,
      42.9%) and C (2, 3.6%) after distal pancreatectomy whereas they were graded as A
      (35, 28.9%), B (15, 12.4%) and C (2, 1.7%) after Whipple procedures. Drain data
      analysis was limited to Whipple procedures because only two patients developed a
      clinically significant leak after distal pancreatectomy. The daily total drain
      output did not differ between patients with a clinical leak (Grades B/C) and
      patients without a clinical leak (no leak and Grade A) on post-operative day
      (POD) 1 to 7. Although the median amylase concentration was significantly higher
      in patients with a clinical leak on POD 1-6, there was no day that amylase
      concentration predicted a clinical leak better than simply classifying all
      patients as 'no leak' (maximum accuracy = 86.1% on POD 1, expected accuracy by
      chance = 85.6%, kappa = 10.2%). CONCLUSION: Drain amylase data in the early post
      operative period are not a sensitive or specific predictor of which patients will
      develop clinically significant POPF after pancreas resection.

PMID- 20815857
TI  - The inconsistent nature of symptomatic pancreatico-jejunostomy anastomotic
      strictures.
AB  - BACKGROUND: Pancreatico-jejunostomy strictures (PJS) after
      pancreatiocoduodenectomy (PD) are poorly understood. METHODS: Patients treated
      for PJS were identified from all PDs (n = 357) performed for all indications in
      our practice (2002 to 2009). Technical aspects of the original operation, as well
      as the presentation, management and outcomes of the resultant stricture were
      assessed. RESULTS: Seven patients developed a symptomatic PJS for an incidence of
      2%. 'Soft' glands and small ducts (</=3 mm) were each present in 3/7 of the
      original anastomoses. Pancreatic fistula occurred in 6/7. The latency period to
      stricture presentation averaged 41 months. Diagnosis of PJS was confirmed by
      secretin magnetic resonance cholangio-pancreatography (MRCP). Therapeutic
      endoscopic retrograde cholangiopancreatography (ERCP) was attempted--each
      unsuccessfully--in four patients. All patients required operative correction of
      their PJS by takedown/revision of the original pancreatico-jejunal anastomoses
      (PJA) (n= 4) +/- a modified Puestow (n= 2). One patient's PJS was completely
      inaccessible due to dense adhesions. Another patient's stricture recurred and was
      successfully revised with a stricturoplasty. At a mean follow-up of 25 months,
      all are alive, but only 4/7 are pain free. CONCLUSION: A symptomatic PJS appears
      to be independent of original pathological, glandular or technical features but
      pancreatic fistulae may contribute. Secretin MRCP is diagnostically useful,
      whereas ERCP has been proven to be therapeutically ineffective. Durable
      resolution of symptoms after surgical revision is unpredictable.

PMID- 20815858
TI  - Pancreatectomy risk calculator: an ACS-NSQIP resource.
AB  - BACKGROUND: The morbidity of pancreatoduodenectomy remains high and the mortality
      may be significantly increased in high-risk patients. However, a method to
      predict post-operative adverse outcomes based on readily available clinical data
      has not been available. Therefore, the objective was to create a 'Pancreatectomy
      Risk Calculator' using the American College of Surgeons-National Surgical Quality
      Improvement Program (ACS-NSQIP) database. METHODS: The 2005-2008 ACS-NSQIP data
      on 7571 patients undergoing proximal (n = 4621), distal (n = 2552) or total
      pancreatectomy (n = 177) as well as enucleation (n = 221) were analysed. Pre
      operative variables (n = 31) were assessed for prediction of post-operative
      mortality, serious morbidity and overall morbidity using a logistic regression
      model. Statistically significant variables were ranked and weighted to create a
      common set of predictors for risk models for all three outcomes. RESULTS: Twenty
      pre-operative variables were statistically significant predictors of post
      operative mortality (2.5%), serious morbidity (21%) or overall morbidity (32%).
      Ten out of 20 significant pre-operative variables were employed to produce the
      three mortality and morbidity risk models. The risk factors included age, gender,
      obesity, sepsis, functional status, American Society of Anesthesiologists (ASA)
      class, coronary heart disease, dyspnoea, bleeding disorder and extent of surgery.
      CONCLUSION: The ACS-NSQIP 'Pancreatectomy Risk Calculator' employs 10 easily
      assessable clinical parameters to assist patients and surgeons in making an
      informed decision regarding the risks and benefits of undergoing pancreatic
      resection. A risk calculator based on this prototype will become available in the
      future as on online ACS-NSQIP resource.

PMID- 20815860
TI  - Abstracts of the Stroke Society of Australasia 21st Annual Scientific Meeting,
      Melbourne, Australia, 1-3 September 2010.

PMID- 20815861
TI  - Review: bringing patient safety to the forefront through structured
      computerisation during clinical handover.
AB  - AIMS AND OBJECTIVES: This review aims to examine critically, the methods and
      modes of delivery of handover used in contemporary health care settings and
      explore the feasibility of a computerised handover system for improving patient
      safety. BACKGROUND: Clinicians play a critical role in promoting patient safety,
      and the handover ritual is recognised as important in exchanging information and
      planning patient care. Communication failures have been identified as an
      important cause of adverse incidents in hospitals. DESIGN: Integrative literature
      review. METHODS: Search of multiple electronic databases using terms: nursing
      handover, handoff, shift-to-shift reporting and change of shift report.
      DISCUSSION: To date, the focus of research has primarily been on the vehicle of
      the handover, rather than the content and processes involved in ensuring the
      reliability and quality of clinical information. Employing a computerised
      handover system in the clinical arena has the potential to improve the quality
      and safety of clinical care. CONCLUSIONS: Whilst the handover performed from
      shift-to-shift is a valuable communication strategy, ambiguities and incomplete
      information can increase the risks of adverse events. Given the importance of
      effective communication, its key link to patient safety and the frequency of
      nursing handover, it is imperative that clinical handover undergo increased
      scrutiny, development and research. RELEVANCE TO CLINICAL PRACTICE: This review
      underscores the challenge in clinical handover and recommends the use of
      technological solutions to improve communication strategies.

PMID- 20815859
TI  - The role of transforming growth factor-beta in suppression of hepatic metastasis
      from colon cancer.
AB  - BACKGROUND: The role of transforming growth factor-beta (TGF-beta) in the
      development of hepatic metastasis from colon cancer is not clearly elucidated.
      The aim of this study was to determine the role of TGF-beta in the development of
      such metastasis. METHODS: Two human colon cancer cell lines were utilized: FET
      alpha cells (intact TGF-beta inhibitory response), and CBS cells (defects in TGF
      beta inhibitory response caused by a deficiency in type II receptor activity).
      The ability of these cell lines to metastasize was analysed in an orthotopic
      colon cancer mouse model. RESULTS: FET-alpha cells did not metastasize to the
      liver, but showed lung metastasis in 10% of the animals, whereas CBS cells gave
      rise to metastasis in 65%. Following the elimination of TGF-beta activity by
      transfection and overexpression of dominant negative type II receptor, FET-alpha
      cells demonstrated liver and lung metastasis in 70% of the animals. Similarly,
      after the restoration of type II receptor activity by ectopic expression, CBS
      cells formed metastasis in fewer (10%) animals. CONCLUSIONS: The results of our
      study demonstrate for the first time that TGF-beta displays selective metastasis
      suppressor activity. These abnormal pathways can serve as selective targets for
      future development of targeted therapies.

PMID- 20815862
TI  - 'The hard work starts now': a glimpse into the lives of carers of community
      dwelling stroke survivors.
AB  - AIMS AND OBJECTIVES: To explore the personal experiences of carers of stroke
      survivors and to elicit their views and opinions of what constitute the major
      issues and concerns of people in their situation. BACKGROUND: The unexpected
      nature of stroke can propel people into the role of carer with little or no
      warning. Some carers of stroke survivors suffer from considerable stress and a
      range of psychological and physical disorders. DESIGN: A small-scale qualitative
      study of experienced carers of stroke survivors. METHOD: Ten carers with
      experience of caring for a stroke survivor were recruited to the study through
      community stroke staff. Data were collected using semi-structured interviews and
      a focus group. RESULTS: The women's main concerns were focused around the need
      for information and support, including the need for some preparation and training
      in the necessary skills of caring. CONCLUSIONS: To understand fully the lives
      that carers lead, it is necessary to explore what carers want to do, and expect
      to do, for the care-recipient. There is a need to develop an understanding of
      factors that appear to be protective against stress, to identify how they can be
      enhanced and to develop ways to minimise the impact of those factors that have a
      detrimental impact on the well-being of carers and on those for whom they care.
      RELEVANCE TO CLINICAL PRACTICE: Health professionals need to ensure that
      appropriate information is clearly provided for carers. Communication between
      health professionals to ensure the 'joined up' provision of therapeutic services
      is another area for continual development. Carers expressed the wish to be better
      prepared to take on the caring role in the home and would have welcomed some
      training in this area.

PMID- 20815863
TI  - Abstract presentations from the AABB Annual Meeting and CTTXPO, Baltimore,
      Maryland, USA, October 9-12, 2010.

PMID- 20815864
TI  - Cross-cultural validity of four quality of life scales in persons with spinal
      cord injury.
AB  - BACKGROUND: Quality of life (QoL) in persons with spinal cord injury (SCI) has
      been found to differ across countries. However, comparability of measurement
      results between countries depends on the cross-cultural validity of the applied
      instruments. The study examined the metric quality and cross-cultural validity of
      the Satisfaction with Life Scale (SWLS), the Life Satisfaction Questionnaire
      (LISAT-9), the Personal Well-Being Index (PWI) and the 5-item World Health
      Organization Quality of Life Assessment (WHOQoL-5) across six countries in a
      sample of persons with spinal cord injury (SCI). METHODS: A cross-sectional multi
      centre study was conducted and the data of 243 out-patients with SCI from study
      centers in Australia, Brazil, Canada, Israel, South Africa, and the United States
      were analyzed using Rasch-based methods. RESULTS: The analyses showed high
      reliability for all 4 instruments (person reliability index .78-.92).
      Unidimensionality of measurement was supported for the WHOQoL-5 (Chi2 = 16.43, df
      = 10, p = .088), partially supported for the PWI (Chi2 = 15.62, df = 16, p =
      .480), but rejected for the LISAT-9 (Chi2 = 50.60, df = 18, p = .000) and the
      SWLS (Chi2 = 78.54, df = 10, p = .000) based on overall and item-wise Chi2 tests,
      principal components analyses and independent t-tests. The response scales showed
      the expected ordering for the WHOQoL-5 and the PWI, but not for the other two
      instruments. Using differential item functioning (DIF) analyses potential cross
      country bias was found in two items of the SWLS and the WHOQoL-5, three items of
      the LISAT-9 and four items of the PWI. However, applying Rasch-based statistical
      methods, especially subtest analyses, it was possible to identify optimal
      strategies to enhance the metric properties and the cross-country equivalence of
      the instruments post-hoc. Following the post-hoc procedures the WHOQOL-5 and the
      PWI worked in a consistent and expected way in all countries. CONCLUSIONS: QoL
      assessment using the summary scores of the WHOQOL-5 and the PWI appeared cross
      culturally valid in persons with SCI. In contrast, summary scores of the LISAT-9
      and the SWLS have to be interpreted with caution. The findings of the current
      study can be especially helpful to select instruments for international research
      projects in SCI.

PMID- 20815865
TI  - Photoperiodic diapause under the control of circadian clock genes in an insect.
AB  - BACKGROUND: Most organisms have evolved a circadian clock in order to anticipate
      daily environmental changes and many of these organisms are also capable of
      sophisticated measurement of daylength (photoperiodism) that is used to regulate
      seasonal events such as diapause, migration and polymorphism. It has been
      generally accepted that the same elements are involved in both circadian (daily)
      and seasonal (annual) rhythms because both rely upon daily light-dark cycles.
      However, as reasonable as this sounds, there remains no conclusive evidence of
      such a molecular machinery in insects. We have approached this issue by using RNA
      interference (RNAi) in Riptortus pedestris. RESULTS: The cuticle deposition
      rhythm exhibited the major properties of circadian rhythms, indicating that the
      rhythm is regulated by a circadian clock. RNAi directed against the circadian
      clock genes of period and cycle, which are negative and positive regulators in
      the circadian clock, respectively, disrupted the cuticle deposition rhythm and
      distinct cuticle layers were produced by these RNAi. Simultaneously, period RNAi
      caused the insect to avert diapause under a diapause-inducing photoperiod whereas
      cycle RNAi induced diapause under a diapause-averting photoperiod. The expression
      patterns of juvenile hormone-regulated genes and the application of juvenile
      hormone analogue suggested that neither ovarian development itself nor a
      downstream cascade of juvenile hormone secretion, were disturbed by period and
      cycle RNAi. CONCLUSIONS: This study revealed that the circadian clock genes are
      crucial not only for daily rhythms but also for photoperiodic diapause. RNAi
      directed against period and cycle had opposite effects not only in the circadian
      cuticle deposition rhythm but also in the photoperiodic diapause. These RNAi also
      had opposite effects on juvenile hormone-regulated gene expression. It is still
      possible that the circadian clock genes pleiotropically affect ovarian
      development but, based on these results, we suggest that the circadian clock
      operated by the circadian clock genes, period and cycle, governs seasonal timing
      as well as the daily rhythms.

PMID- 20815866
TI  - Simulated effect of pneumococcal vaccination in the Netherlands on existing rules
      constructed in a non-vaccinated cohort predicting sequelae after bacterial
      meningitis.
AB  - BACKGROUND: Previously two prediction rules identifying children at risk of
      hearing loss and academic or behavioral limitations after bacterial meningitis
      were developed. Streptococcus pneumoniae as causative pathogen was an important
      risk factor in both. Since 2006 Dutch children receive seven-valent conjugate
      vaccination against S. pneumoniae. The presumed effect of vaccination was
      simulated by excluding all children infected by S. pneumoniae with the serotypes
      included in the vaccine, from both previous collected cohorts (between 1990
      1995). METHODS: Children infected by one of the vaccine serotypes were excluded
      from both original cohorts (hearing loss: 70 of 628 children; academic or
      behavioral limitations: 26 of 182 children). All identified risk factors were
      included in multivariate logistic regression models. The discriminative ability
      of both new models was calculated. RESULTS: The same risk factors as in the
      original models were significant. The discriminative ability of the original
      hearing loss model was 0.84 and of the new model 0.87. In the academic or
      behavioral limitations model it was 0.83 and 0.84 respectively. CONCLUSION: It
      can be assumed that the prediction rules will also be applicable on a vaccinated
      population. However, vaccination does not provide 100% coverage and evidence is
      available that serotype replacement will occur. The impact of vaccination on
      serotype replacement needs to be investigated, and the prediction rules must be
      validated externally.

PMID- 20815867
TI  - Spatial heterogeneity and temporal evolution of malaria transmission risk in
      Dakar, Senegal, according to remotely sensed environmental data.
AB  - BACKGROUND: The United Nations forecasts that by 2050, more than 60% of the
      African population will live in cities. Thus, urban malaria is considered an
      important emerging health problem in that continent. Remote sensing (RS) and
      geographic information systems (GIS) are useful tools for addressing the
      challenge of assessing, understanding and spatially focusing malaria control
      activities. The objectives of the present study were to use high spatial
      resolution SPOT (Satellite Pour l'Observation de la Terre) satellite images to
      identify some urban environmental factors in Dakar associated with Anopheles
      arabiensis densities, to assess the persistence of these associations and to
      describe spatial changes in at-risk environments using a decadal time scale.
      METHODS: Two SPOT images from the 1996 and 2007 rainy seasons in Dakar were
      processed to extract environmental factors, using supervised classification of
      land use and land cover, and a calculation of NDVI (Normalized Difference
      Vegetation Index) and distance to vegetation. Linear regressions were fitted to
      identify the ecological factors associated with An. arabiensis aggressiveness
      measured in 1994-97 in the South and centre districts of Dakar. Risk maps for
      populated areas were computed and compared for 1996 and 2007 using the results of
      the statistical models. RESULTS: Almost 60% of the variability in anopheline
      aggressiveness measured in 1994-97 was explained with only one variable: the
      built-up area in a 300-m radius buffer around the catching points. This
      association remained stable between 1996 and 2007. Risk maps were drawn by
      inverting the statistical association. The total increase of the built-up areas
      in Dakar was about 30% between 1996 and 2007. In proportion to the total
      population of the city, the population at high risk for malaria fell from 32% to
      20%, whereas the low-risk population rose from 29 to 41%. CONCLUSIONS:
      Environmental data retrieved from high spatial resolution SPOT satellite images
      were associated with An. arabiensis densities in Dakar urban setting, which
      allowed to generate malaria transmission risk maps. The evolution of the risk was
      quantified, and the results indicated there are benefits of urbanization in
      Dakar, since the proportion of the low risk population increased while
      urbanization progressed.

PMID- 20815869
TI  - Cost-effectiveness of tailored print communication, telephone motivational
      interviewing, and a combination of the two: results of an economic evaluation
      alongside the Vitalum randomized controlled trial.
AB  - BACKGROUND: The aim of the present study was to evaluate the cost-effectiveness
      of tailored print communication (TPC), telephone motivational interviewing (TMI),
      a combination of the two, and no intervention on two outcomes in adults aged 45
      to 70, half of them having hypertension: increasing the number of public health
      guidelines met for three behaviors (physical activity and fruit and vegetable
      consumption), and impact on quality adjusted life years (QALYs). METHODS:
      Participants (n = 1,629) from 23 Dutch general practices were randomized into one
      of four groups, which received 4 TPCs, 4 TMIs, 2 of each (combined), or no
      intervention (control), respectively. The self-reported outcomes, measured at
      baseline and 73 weeks follow-up (7 months after the last intervention component),
      were difference in total number of guidelines met at follow-up compared to
      baseline, and number of QALYs experienced over 73 weeks. The costs of
      implementing the intervention were estimated using a bottom-up approach. RESULTS:
      At 73 weeks follow-up participants showed increased adherence with 0.62 (TPC),
      0.40 (TMI), 0.50 (combined), and 0.26 (control) guidelines compared to baseline,
      and experienced 1.09, 1.08, 1.08, and 1.07 QALYs, respectively. The costs for the
      control group were considered to be zero. TMI was more expensive (?107 per
      person) than both the combined intervention (?80) and TPC (?57). The control
      condition was most cost-effective for lower ceiling ratios, while TPC had the
      highest probability of being most cost-effective for higher ceiling ratios (more
      than ?160 per additional guideline met, and ?2,851 for each individual QALY).
      CONCLUSIONS: For low society's willingness to pay, the control group was most
      cost-effective for the number of QALYs experienced over 73 weeks. This also
      applied to the increase in the number of guidelines met at lower ceiling ratios,
      whereas at higher ceiling ratios, TPC had a higher probability of being more cost
      effective than the TMI, combined or control conditions. This also seemed to apply
      for QALYs experienced over 73 weeks. More research is needed on the long-term
      efficacy of both TPC and TMI, as well as on how to increase their cost
      effectiveness. TRIAL REGISTRATION: Dutch Trial Register NTR1068.

PMID- 20815870
TI  - Insomnia and its correlates in a representative sample of the Greek population.
AB  - BACKGROUND: Insomnia is a major public health concern affecting about 10% of the
      general population in its chronic form. Furthermore, epidemiological surveys
      demonstrate that poor sleep and sleep dissatisfaction are even more frequent
      problems (10-48%) in the community. This is the first report on the prevalence of
      insomnia in Greece, a southeastern European country which differs in several
      socio-cultural and climatic aspects from the rest of European Community members.
      Data obtained from a national household survey (n = 1005) were used to assess the
      relationship between insomnia symptoms and a variety of sociodemographic
      variables, life habits, and health-related factors. METHODS: A self-administered
      questionnaire with questions pertaining to general health and related issues was
      given to the participants. The Short Form-36 (Mental Health subscale), the Athens
      Insomnia Scale (AIS) as a measure of insomnia-related symptoms, and the
      International Physical Activity Questionnaire (IPAQ) were also used for the
      assessment. RESULTS: The prevalence of insomnia in the total sample was 25.3% (n
      = 254); insomnia was more frequent in women than men (30.7% vs. 19.5%) and
      increased with age. Multiple regression analysis revealed a significant
      association of insomnia with low socio-economical status and educational level,
      physical inactivity, existence of a chronic physical or mental disease and
      increased number of hospitalizations in the previous year. CONCLUSIONS: The
      present study confirms most findings reported from other developed countries
      around the world regarding the high prevalence of insomnia problems in the
      general population and their association with several sociodemographic and health
      related predisposing factors. These results further indicate the need for more
      active interventions on the part of physicians who should suspect and
      specifically ask about such symptoms.

PMID- 20815871
TI  - Combination of diffusion tensor and functional magnetic resonance imaging during
      recovery from the vegetative state.
AB  - BACKGROUND: The rate of recovery from the vegetative state (VS) is low.
      Currently, little is known of the mechanisms and cerebral changes that accompany
      those relatively rare cases of good recovery. Here, we combined functional
      magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to study the
      evolution of one VS patient at one month post-ictus and again twelve months later
      when he had recovered consciousness. METHODS: fMRI was used to investigate
      cortical responses to passive language stimulation as well as task-induced
      deactivations related to the default-mode network. DTI was used to assess the
      integrity of the global white matter and the arcuate fasciculus. We also
      performed a neuropsychological assessment at the time of the second MRI
      examination in order to characterize the profile of cognitive deficits. RESULTS:
      fMRI analysis revealed anatomically appropriate activation to speech in both the
      first and the second scans but a reduced pattern of task-induced deactivations in
      the first scan. In the second scan, following the recovery of consciousness, this
      pattern became more similar to that classically described for the default-mode
      network. DTI analysis revealed relative preservation of the arcuate fasciculus
      and of the global normal-appearing white matter at both time points. The
      neuropsychological assessment revealed recovery of receptive linguistic
      functioning by 12-months post-ictus. CONCLUSIONS: These results suggest that the
      combination of different structural and functional imaging modalities may provide
      a powerful means for assessing the mechanisms involved in the recovery from the
      VS.

PMID- 20815872
TI  - Systematic evaluation of implementation fidelity of complex interventions in
      health and social care.
AB  - BACKGROUND: Evaluation of an implementation process and its fidelity can give
      insight into the 'black box' of interventions. However, a lack of standardized
      methods for studying fidelity and implementation process have been reported,
      which might be one reason for the fact that few prior studies in the field of
      health service research have systematically evaluated interventions'
      implementation processes.The aim of this project is to systematically evaluate
      implementation fidelity and possible factors influencing fidelity of complex
      interventions in health and social care. METHODS: A modified version of The
      Conceptual Framework for Implementation Fidelity will be used as a conceptual
      model for the evaluation. The modification implies two additional moderating
      factors: context and recruitment. A systematic evaluation process was developed.
      Multiple case study method is used to investigate implementation of three complex
      health service interventions. Each case will be investigated in depth and
      longitudinally, using both quantitative and qualitative methods. DISCUSSION: This
      study is the first attempt to empirically test The Conceptual Framework for
      Implementation Fidelity. The study can highlight mechanism and factors of
      importance when implementing complex interventions. Especially the role of the
      moderating factors on implementation fidelity can be clarified. TRIAL
      REGISTRATION: Supported Employment, SE, among people with severe mental illness -
      a randomized controlled trial: NCT00960024.

PMID- 20815868
TI  - European consensus statement on diagnosis and treatment of adult ADHD: The
      European Network Adult ADHD.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is among the most
      common psychiatric disorders of childhood that persists into adulthood in the
      majority of cases. The evidence on persistence poses several difficulties for
      adult psychiatry considering the lack of expertise for diagnostic assessment,
      limited treatment options and patient facilities across Europe. METHODS: The
      European Network Adult ADHD, founded in 2003, aims to increase awareness of this
      disorder and improve knowledge and patient care for adults with ADHD across
      Europe. This Consensus Statement is one of the actions taken by the European
      Network Adult ADHD in order to support the clinician with research evidence and
      clinical experience from 18 European countries in which ADHD in adults is
      recognised and treated. RESULTS: Besides information on the genetics and
      neurobiology of ADHD, three major questions are addressed in this statement: (1)
      What is the clinical picture of ADHD in adults? (2) How can ADHD in adults be
      properly diagnosed? (3) How should ADHD in adults be effectively treated?
      CONCLUSIONS: ADHD often presents as an impairing lifelong condition in adults,
      yet it is currently underdiagnosed and treated in many European countries,
      leading to ineffective treatment and higher costs of illness. Expertise in
      diagnostic assessment and treatment of ADHD in adults must increase in
      psychiatry. Instruments for screening and diagnosis of ADHD in adults are
      available and appropriate treatments exist, although more research is needed in
      this age group.

PMID- 20815874
TI  - T regulatory cells and attenuated bleomycin-induced fibrosis in lungs of CCR7-/-
      mice.
AB  - BACKGROUND: C-C chemokine receptor (CCR)7 is a regulator of dendritic cell and T
      cell migration, and its role in tissue wound healing has been investigated in
      various disease models. We have previously demonstrated that CCR7 and its ligand,
      chemokine (C-C motif) ligand (CCL)21, modulates wound repair in pulmonary
      fibrosis (PF) but the mechanism of this is unknown. The objective of this study
      was to investigate whether the absence of CCR7 protects against bleomycin (BLM)
      induced PF. CCR7-/- mice failed to mount a fibrotic pulmonary response as
      assessed by histologic collagen staining and quantification by hydroxyproline. We
      hypothesized that the prominent characteristics of CCR7-/- mice, including
      elevated levels of cytokine and chemokine mediators and the presence of bronchus
      associated lymphoid tissue (BALT) might be relevant to the protective phenotype.
      RESULTS: Pulmonary fibrosis was induced in CCR7+/+ and CCR7-/- mice via a single
      intratracheal injection of BLM. We found that the lung cytokine/chemokine milieu
      associated with the absence of CCR7 correlated with an increase in BALT, and
      might be attributable to regulatory T cell (Treg) homeostasis and trafficking
      within the lungs and lymph nodes. In response to BLM challenge, CCR7-/- mice
      exhibited an early, steady increase in lung CD4+ T cells and increased CD4+ CD25+
      FoxP3+ Tregs in the lungs 21 days after challenge. These findings are consistent
      with increased lung expression of interleukin-2 and indoleamine 2,3-dioxygenase
      in CCR7-/- mice, which promote Treg expansion. CONCLUSIONS: Our study
      demonstrates that the protective phenotype associated with BLM-treated CCR7-/-
      mice correlates with the presence of BALT and the anchoring of Tregs in the lungs
      of CCR7-/- mice. These data provide novel evidence to support the further
      investigation of CCR7-mediated Treg trafficking in the modulation of BLM-induced
      PF.

PMID- 20815875
TI  - Sub-national assessment of inequality trends in neonatal and child mortality in
      Brazil.
AB  - OBJECTIVE: Brazil's large socioeconomic inequalities together with the increase
      in neonatal mortality jeopardize the MDG-4 child mortality target by 2015. We
      measured inequality trends in neonatal and under five mortality across
      municipalities characterized by their socio-economic status in a period where
      major pro poor policies were implemented in Brazil to infer whether policies and
      interventions in newborn and child health have been successful in reaching the
      poor as well as the better off. METHODS: Using data from the 5,507 municipalities
      in 1991 and 2000, we developed accurate estimates of neonatal mortality at
      municipality level and used these data to investigate inequality trends in
      neonatal and under five mortality across municipalities characterized by socio
      economic status. RESULTS: Child health policies and interventions have been more
      effective in reaching the better off than the worst off. Reduction of under five
      mortality at national level has been achieved by reducing the level of under five
      mortality among the better off. Poor municipalities suffer from worse newborn and
      child health than richer municipalities and the poor/rich gaps have increased.
      CONCLUSION: Our analysis highlights the importance of monitoring progress on MDGs
      at sub-national level and measuring inequality gaps to accurately target health
      and inter-sectoral policies. Further efforts are required to improve the
      measurement and monitoring of trends in neonatal and under five mortality at sub
      national level, particularly in developing countries and countries with large
      socioeconomic inequalities.

PMID- 20815876
TI  - Modeling the airborne survival of influenza virus in a residential setting: the
      impacts of home humidification.
AB  - BACKGROUND: Laboratory research studies indicate that aerosolized influenza
      viruses survive for longer periods at low relative humidity (RH) conditions.
      Further analysis has shown that absolute humidity (AH) may be an improved
      predictor of virus survival in the environment. Maintaining airborne moisture
      levels that reduce survival of the virus in the air and on surfaces could be
      another tool for managing public health risks of influenza. METHODS: A multi-zone
      indoor air quality model was used to evaluate the ability of portable humidifiers
      to control moisture content of the air and the potential related benefit of
      decreasing survival of influenza viruses in single-family residences. We modeled
      indoor AH and influenza virus concentrations during winter months (Northeast US)
      using the CONTAM multi-zone indoor air quality model. A two-story residential
      template was used under two different ventilation conditions - forced hot air and
      radiant heating. Humidity was evaluated on a room-specific and whole house basis.
      Estimates of emission rates for influenza virus were particle-size specific and
      derived from published studies and included emissions during both tidal breathing
      and coughing events. The survival of the influenza virus was determined based on
      the established relationship between AH and virus survival. RESULTS: The presence
      of a portable humidifier with an output of 0.16 kg water per hour in the bedroom
      resulted in an increase in median sleeping hours AH/RH levels of 11 to 19%
      compared to periods without a humidifier present. The associated percent decrease
      in influenza virus survival was 17.5 - 31.6%. Distribution of water vapor through
      a residence was estimated to yield 3 to 12% increases in AH/RH and 7.8-13.9%
      reductions in influenza virus survival. CONCLUSION: This modeling analysis
      demonstrates the potential benefit of portable residential humidifiers in
      reducing the survival of aerosolized influenza virus by controlling humidity
      indoors.

PMID- 20815878
TI  - Plasma bile acids are not associated with energy metabolism in humans.
AB  - Bile acids (BA) have recently been shown to increase energy expenditure in mice,
      but this concept has not been tested in humans. Therefore, we investigated the
      relationship between plasma BA levels and energy expenditure in humans. Type 2
      diabetic (T2DM) patients (n = 12) and gender, age and BMI-matched healthy
      controls (n = 12) were studied before and after 8 weeks of treatment with a BA
      sequestrant. In addition, patients with liver cirrhosis (n = 46) were
      investigated, since these display elevated plasma BA together with increased
      energy expenditure. This group was compared to gender-, age- and BMI-matched
      healthy controls (n = 20). Fasting plasma levels of total BA and individual BA
      species as well as resting energy expenditure were determined. In response to
      treatment with the BA sequestrant, plasma deoxycholic acid (DCA) levels decreased
      in controls (-60%, p < 0.05) and T2DM (-32%, p < 0.05), while chenodeoxycholic
      acid (CDCA) decreased in controls only (-33%, p < 0.05). Energy expenditure did
      not differ between T2DM and controls at baseline and, in contrast to plasma BA
      levels, was unaffected by treatment with the BA sequestrant. Total BA as well as
      individual BA species did not correlate with energy expenditure at any time
      throughout the study. Patients with cirrhosis displayed on average an increase in
      energy expenditure of 18% compared to values predicted by the Harris-Benedict
      equation, and plasma levels of total BA (up to 12-fold) and individual BA (up to
      20-fold) were increased over a wide range. However, neither total nor individual
      plasma BA levels correlated with energy expenditure. In addition, energy
      expenditure was identical in patients with a cholestatic versus a non-cholestatic
      origin of liver disease while plasma total BA levels differed four-fold between
      the groups. In conclusion, in the various (patho)physiological conditions
      studied, plasma BA levels were not associated with changes in energy expenditure.
      Therefore, our data do not support an important role of circulating BA in the
      control of human energy metabolism.

PMID- 20815877
TI  - Cooperative and individualistic functions of the microRNAs in the miR-23a~27a~24
      2 cluster and its implication in human diseases.
AB  - The small RNA molecules of about 19-22 nucleotides in length, aptly called
      microRNAs, perform the task of gene regulation in the cell. Interestingly, till
      the early nineties very little was known about them but eventually, the microRNAs
      have become forefront in the area of research. The huge number of microRNAs plus
      each one of them targeting a vast number of related as well as unrelated genes
      makes them very interesting molecules to study. To add to the mystery of miRNAs
      is the fact that the same miRNA can have antagonizing role in two different cell
      types i.e. in one cell type; the miRNA promotes proliferation whereas in another
      cell type the same miRNA inhibits proliferation. Another remarkable aspect of the
      microRNAs is that many of them exist in clusters. In humans alone, out of 721
      microRNAs known, 247 of them occur in 64 clusters at an inter-miRNA distance of
      less than 5000 bp. The reason for this clustering of miRNAs is not fully
      understood but since the miRNA clusters are evolutionary conserved, their
      significance cannot be ruled out. The objective of this review is to summarize
      the recent progress on the functional characterization of miR-23a~27a~24-2
      cluster in humans in relation to various health and diseased conditions and to
      highlight the cooperative effects of the miRNAs of this cluster.

PMID- 20815879
TI  - Early clinical development of artemether-lumefantrine dispersible tablet:
      palatability of three flavours and bioavailability in healthy subjects.
AB  - BACKGROUND: Efforts to ease administration and enhance acceptability of the oral
      anti-malarial artemether-lumefantrine (A-L) crushed tablet to infants and
      children triggered the development of a novel dispersible tablet of A-L. During
      early development of this new formulation, two studies were performed in healthy
      subjects, one to evaluate the palatability of three flavours of A-L, and a second
      one to compare the bioavailability of active principles between the dispersible
      tablet and the tablet (administered crushed and intact). METHODS: Study 1 was
      performed in 48 healthy schoolchildren in Tanzania. Within 1 day, all subjects
      tasted a strawberry-, orange- and cherry-flavoured oral A-L suspension for 10
      seconds (without swallowing) in a randomized, single-blind, crossover fashion.
      The palatability of each formulation was rated using a visual analogue scale
      (VAS). Study 2 was an open, randomized crossover trial in 48 healthy adults given
      single doses of A-L (80 mg artemether + 480 mg lumefantrine) with food. The
      objectives were to compare the bioavailability of artemether, dihydroartemisinin
      (DHA) and lumefantrine between the dispersible tablet and the tablet administered
      crushed (primary objective) and intact (secondary objective). RESULTS: Study 1
      showed no statistically significant difference in VAS scores between the three
      flavours but cherry had the highest score in several ratings (particularly for
      overall liking). Study 2 demonstrated that the dispersible and crushed tablets
      delivered bioequivalent artemether, DHA and lumefantrine systemic exposure (area
      under the curve [AUC]); mean +/- SD AUC0-tlast were 208 +/- 113 vs 195 +/- 93
      h.ng/ml for artemether, 206 +/- 81 vs 199 +/- 84 h.ng/ml for DHA and 262 +/- 107
      vs 291 +/- 106 h x MUg/ml for lumefantrine. Bioequivalence was also shown for
      peak plasma concentrations (Cmax) of DHA and lumefantrine. Compared with the
      intact tablet, the dispersible tablet resulted in bioequivalent lumefantrine
      exposure, but AUC and Cmax values of artemether and DHA were 20-35% lower.
      CONCLUSIONS: Considering that cherry was the preferred flavour, and that the
      novel A-L dispersible tablet demonstrated similar pharmacokinetic performances to
      the tablet administered crushed, a cherry-flavoured A-L dispersible tablet
      formulation was selected for further development and testing in a large efficacy
      and safety study in African children with malaria.

PMID- 20815881
TI  - Sample size and statistical power considerations in high-dimensionality data
      settings: a comparative study of classification algorithms.
AB  - BACKGROUND: data generated using 'omics' technologies are characterized by high
      dimensionality, where the number of features measured per subject vastly exceeds
      the number of subjects in the study. In this paper, we consider issues relevant
      in the design of biomedical studies in which the goal is the discovery of a
      subset of features and an associated algorithm that can predict a binary outcome,
      such as disease status. We compare the performance of four commonly used
      classifiers (K-Nearest Neighbors, Prediction Analysis for Microarrays, Random
      Forests and Support Vector Machines) in high-dimensionality data settings. We
      evaluate the effects of varying levels of signal-to-noise ratio in the dataset,
      imbalance in class distribution and choice of metric for quantifying performance
      of the classifier. To guide study design, we present a summary of the key
      characteristics of 'omics' data profiled in several human or animal model
      experiments utilizing high-content mass spectrometry and multiplexed immunoassay
      based techniques. RESULTS: the analysis of data from seven 'omics' studies
      revealed that the average magnitude of effect size observed in human studies was
      markedly lower when compared to that in animal studies. The data measured in
      human studies were characterized by higher biological variation and the presence
      of outliers. The results from simulation studies indicated that the classifier
      Prediction Analysis for Microarrays (PAM) had the highest power when the class
      conditional feature distributions were Gaussian and outcome distributions were
      balanced. Random Forests was optimal when feature distributions were skewed and
      when class distributions were unbalanced. We provide a free open-source R
      statistical software library (MVpower) that implements the simulation strategy
      proposed in this paper. CONCLUSION: no single classifier had optimal performance
      under all settings. Simulation studies provide useful guidance for the design of
      biomedical studies involving high-dimensionality data.

PMID- 20815880
TI  - At the interface of community and healthcare systems: a longitudinal cohort study
      on evolving health and the impact of primary healthcare from the patient's
      perspective.
AB  - BACKGROUND: Massive efforts in Canada have been made to renew primary healthcare.
      However, although early evaluations of initiatives and research on certain
      aspects of the reform are promising, none have examined the link between patient
      assessments of care and health outcomes or the impacts at a population level. The
      goal of this project is to examine the effect of patient-centred and effective
      primary healthcare on the evolution of chronic illness burden and health
      functioning in a population, and in particularly vulnerable groups: the multi
      morbid and the poor. METHODS/DESIGN: A randomly selected cohort of 2000 adults
      aged 25 to 75 years will be recruited within the geographic boundaries of four
      local healthcare networks in Quebec. At recruitment, cohort members will report
      on socio-demographic information, functional health and healthcare use. Two
      weeks, 12 months and 24 months after recruitment, cohort participants will
      complete a self-administered questionnaire on current health and health
      behaviours in order to evaluate primary healthcare received in the previous
      year.The dependent variables are calculated as change over time of functional
      health status, chronic illness burden, and health behaviours. Dimensions of
      patient-centred care and clinical processes are measured using sub-scales of
      validated instruments. We will use Poisson regression modelling to estimate the
      incidence rate of chronic illness burden scores and structural equation modelling
      to explore relationships between variables and to examine the impact of
      dimensions of patient-centred care and effective primary healthcare. DISCUSSION:
      Results will provide valuable information for primary healthcare clinicians on
      the course of chronic illness over time and the impact on health outcomes of
      accessible, patient-centred and effective care. A demonstration of impact will
      contribute to the promotion of continuous quality improvement activities at a
      clinical level. While considerable advances have been made in the management of
      specific chronic illnesses, this will make a unique contribution to effective
      care for persons with multiple morbidities. Furthermore, the cohort and data
      architecture will serve as a research platform for future projects.

PMID- 20815882
TI  - Community contextual predictors of endoscopic colorectal cancer screening in the
      USA: spatial multilevel regression analysis.
AB  - BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer death
      in the United States, and endoscopic screening can both detect and prevent
      cancer, but utilization is suboptimal and varies across geographic regions. We
      use multilevel regression to examine the various predictors of individuals'
      decisions to utilize endoscopic CRC screening. Study subjects are a 100%
      population cohort of Medicare beneficiaries identified in 2001 and followed
      through 2005. The outcome variable is a binary indicator of any sigmoidoscopy or
      colonoscopy use over this period. We analyze each state separately and map the
      findings for all states together to reveal patterns in the observed heterogeneity
      across states. RESULTS: We estimate a fully adjusted model for each state, based
      on a comprehensive socio-ecological model. We focus the discussion on the
      independent contributions of each of three community contextual variables that
      are amenable to policy intervention. Prevalence of Medicare managed care in one's
      neighborhood was associated with lower probability of screening in 12 states and
      higher probability in 19 states. Prevalence of poor English language ability
      among elders in one's neighborhood was associated with lower probability of
      screening in 15 states and higher probability in 6 states. Prevalence of poverty
      in one's neighborhood was associated with lower probability of screening in 36
      states and higher probability in 5 states. CONCLUSIONS: There are considerable
      differences across states in the socio-ecological context of CRC screening by
      endoscopy, suggesting that the current decentralized configuration of state
      specific comprehensive cancer control programs is well suited to respond to the
      observed heterogeneity. We find that interventions to mediate language barriers
      are more critically needed in some states than in others. Medicare managed care
      penetration, hypothesized to affect information about and diffusion of new
      endoscopic technologies, has a positive association in only a minority of states.
      This suggests that managed care plans' promotion of this cost-increasing
      technology has been rather limited. Area poverty has a negative impact in the
      vast majority of states, but is positive in five states, suggesting there are
      some effective cancer control policies in place targeting the poor with
      supplemental resources promoting CRC screening.

PMID- 20815883
TI  - Multiple imputation for estimation of an occurrence rate in cohorts with
      attrition and discrete follow-up time points: a simulation study.
AB  - BACKGROUND: In longitudinal cohort studies, subjects may be lost to follow-up at
      any time during the study. This leads to attrition and thus to a risk of
      inaccurate and biased estimations. The purpose of this paper is to show how
      multiple imputation can take advantage of all the information collected during
      follow-up in order to estimate the cumulative probability P(E) of an event E,
      when the first occurrence of this event is observed at t successive time points
      of a longitudinal study with attrition. METHODS: We compared the performance of
      multiple imputation with that of Kaplan-Meier estimation in several simulated
      attrition scenarios. RESULTS: In missing-completely-at-random scenarios, the
      multiple imputation and Kaplan-Meier methods performed well in terms of bias
      (less than 1%) and coverage rate (range = [94.4%; 95.8%]). In missing-at-random
      scenarios, the Kaplan-Meier method was associated with a bias ranging from -5.1%
      to 7.0% and with a very poor coverage rate (as low as 0.2%). Multiple imputation
      performed much better in this situation (bias <2%, coverage rate >83.4%).
      CONCLUSIONS: Multiple imputation shows promise for estimation of an occurrence
      rate in cohorts with attrition. This study is a first step towards defining
      appropriate use of multiple imputation in longitudinal studies.

PMID- 20815884
TI  - Sub-chronic lung inflammation after airway exposures to Bacillus thuringiensis
      biopesticides in mice.
AB  - BACKGROUND: The aim of the present study was to assess possible health effects of
      airway exposures to Bacillus thuringiensis (Bt) based biopesticides in mice.
      Endpoints were lung inflammation evaluated by presence of inflammatory cells in
      bronchoalveolar lavage fluid (BALF), clearance of bacteria from the lung lumen
      and histological alterations of the lungs. Hazard identifications of the
      biopesticides were carried out using intratracheal (i.t.) instillation, followed
      by an inhalation study. The two commercial biopesticides used were based on the
      Bt. subspecies kurstaki and israelensis, respectively. Groups of BALB/c mice were
      i.t instilled with one bolus (3.5 * 105 or 3.4 * 106 colony forming units (CFU)
      per mouse) of either biopesticide. Control mice were instilled with sterile
      water. BALFs were collected and the inflammatory cells were counted and
      differentiated. The BALFs were also subjected to CFU counts. RESULTS: BALF
      cytology showed an acute inflammatory response dominated by neutrophils 24 hours
      after instillation of biopesticide. Four days after instillation, the neutrophil
      number was normalised and inflammation was dominated by lymphocytes and
      eosinophils, whereas 70 days after instillation, the inflammation was
      interstitially located with few inflammatory cells present in the lung lumen.Half
      of the instilled mice had remaining CFU recovered from BALF 70 days after
      exposure. To gain further knowledge with relevance for risk assessment, mice were
      exposed to aerosols of biopesticide one hour per day for 2 * 5 days. Each mouse
      received 1.9 * 104 CFU Bt israelensis or 2.3 * 103 CFU Bt kurstaki per exposure.
      Seventy days after end of the aerosol exposures, 3 out of 17 mice had
      interstitial lung inflammation. CFU could be recovered from 1 out of 10 mice 70
      days after exposure to aerosolised Bt kurstaki. Plethysmography showed that
      inhalation of Bt aerosol did not induce airway irritation. CONCLUSIONS: Repeated
      low dose aerosol exposures to commercial Bt based biopesticides can induce sub
      chronic lung inflammation in mice, which may be the first step in the development
      of chronic lung diseases. Inhalation of Bt aerosols does not induce airway
      irritation, which could explain why workers may be less inclined to use a filter
      mask during the application process, and are thereby less protected from exposure
      to Bt spores.

PMID- 20815885
TI  - Insertion torque is not a good predictor of pedicle screw loosening after spinal
      instrumentation: a prospective study in 8 patients.
AB  - BACKGROUND: Pedicle screw loosening is a major safety concern in instrumented
      spinal surgery due to loosening with potential pseudarthrosis and possible loss
      of correction requiring revision surgery. Several cadaver studies have compared
      insertion torque of pedicle screws with resistance to pullout or cyclic loading.
      In most of these studies, a correlation has been found between these variables.
      Clinical studies have been made, comparing insertion torque to bone mineral
      density or radiological signs of screw loosening. There are no clinical studies
      comparing insertion torque to extraction torque or other biomechanical parameters
      in vivo. This study was designed to investigate whether the insertion torque of
      pedicle screws can be used to predict the purchase of the screws. METHODS: The
      insertion torque of stainless steel pedicle screws was recorded in eight patients
      undergoing lumbar fusion surgery with four-screw constructs. Torque gauge
      manometers were used for the recordings. The implants were removed after one
      year, and the extraction torque of the screws was recorded. RESULTS: The mean
      insertion torque was 76 +/- 41 Ncm and the mean extraction torque 29 +/- 36 Ncm.
      The r value was 0.591, suggesting that there was a correlation between the
      insertion and extraction torque. However, the scattergram revealed that the
      screws could be divided into two groups, six screws with a high correlation
      between insertion and extraction torque, and 26 screws where no correlation could
      be demonstrated. CONCLUSIONS: In this unique human in-vivo study, the insertion
      torque could not be used to predict the purchase of lumbar pedicle screws one
      year after implantation. It could be demonstrated that in vivo insertion torque
      alone is of minor value to estimate pullout strength, and should be combined with
      or replaced by more accurate measures.

PMID- 20815886
TI  - Comparison of information-theoretic to statistical methods for gene-gene
      interactions in the presence of genetic heterogeneity.
AB  - BACKGROUND: Multifactorial diseases such as cancer and cardiovascular diseases
      are caused by the complex interplay between genes and environment. The detection
      of these interactions remains challenging due to computational limitations.
      Information theoretic approaches use computationally efficient directed search
      strategies and thus provide a feasible solution to this problem. However, the
      power of information theoretic methods for interaction analysis has not been
      systematically evaluated. In this work, we compare power and Type I error of an
      information-theoretic approach to existing interaction analysis methods. METHODS:
      The k-way interaction information (KWII) metric for identifying variable
      combinations involved in gene-gene interactions (GGI) was assessed using several
      simulated data sets under models of genetic heterogeneity driven by
      susceptibility increasing loci with varying allele frequency, penetrance values
      and heritability. The power and proportion of false positives of the KWII was
      compared to multifactor dimensionality reduction (MDR), restricted partitioning
      method (RPM) and logistic regression. RESULTS: The power of the KWII was
      considerably greater than MDR on all six simulation models examined. For a given
      disease prevalence at high values of heritability, the power of both RPM and KWII
      was greater than 95%. For models with low heritability and/or genetic
      heterogeneity, the power of the KWII was consistently greater than RPM; the
      improvements in power for the KWII over RPM ranged from 4.7% to 14.2% at for
      alpha = 0.001 in the three models at the lowest heritability values examined.
      KWII performed similar to logistic regression. CONCLUSIONS: Information theoretic
      models are flexible and have excellent power to detect GGI under a variety of
      conditions that characterize complex diseases.

PMID- 20815887
TI  - Tetracycline-controlled transgene activation using the ROSA26-iM2-GFP knock-in
      mouse strain permits GFP monitoring of DOX-regulated transgene-expression.
AB  - BACKGROUND: Conditional gene activation is an efficient strategy for studying
      gene function in genetically modified animals. Among the presently available gene
      switches, the tetracycline-regulated system has attracted considerable interest
      because of its unique potential for reversible and adjustable gene regulation.
      RESULTS: To investigate whether the ubiquitously expressed Gt(ROSA)26Sor locus
      enables uniform DOX-controlled gene expression, we inserted the improved
      tetracycline-regulated transcription activator iM2 together with an iM2 dependent
      GFP gene into the Gt(ROSA)26Sor locus, using gene targeting to generate ROSA26
      iM2-GFP (R26t1Delta) mice. Despite the presence of ROSA26 promoter driven iM2,
      R26t1Delta mice showed very sparse DOX-activated expression of different iM2
      responsive reporter genes in the brain, mosaic expression in peripheral tissues
      and more prominent expression in erythroid, myeloid and lymphoid lineages, in
      hematopoietic stem and progenitor cells and in olfactory neurons. CONCLUSIONS:
      The finding that gene regulation by the DOX-activated transcriptional factor iM2
      in the Gt(ROSA)26Sor locus has its limitations is of importance for future
      experimental strategies involving transgene activation from the endogenous ROSA26
      promoter. Furthermore, our ROSA26-iM2 knock-in mouse model (R26t1Delta)
      represents a useful tool for implementing gene function in vivo especially under
      circumstances requiring the side-by-side comparison of gene manipulated and wild
      type cells. Since the ROSA26-iM2 mouse allows mosaic gene activation in
      peripheral tissues and haematopoietic cells, this model will be very useful for
      uncovering previously unknown or unsuspected phenotypes.

PMID- 20815888
TI  - Pandemic influenza control in Europe and the constraints resulting from
      incoherent public health laws.
AB  - BACKGROUND: With the emergence of influenza H1N1v the world is facing its first
      21st century global pandemic. Severe Acute Respiratory Syndrome (SARS) and avian
      influenza H5N1 prompted development of pandemic preparedness plans. National
      systems of public health law are essential for public health stewardship and for
      the implementation of public health policy. International coherence will
      contribute to effective regional and global responses. However little research
      has been undertaken on how law works as a tool for disease control in Europe.
      With co-funding from the European Union, we investigated the extent to which laws
      across Europe support or constrain pandemic preparedness planning, and whether
      national differences are likely to constrain control efforts. METHODS: We
      undertook a survey of national public health laws across 32 European states using
      a questionnaire designed around a disease scenario based on pandemic influenza.
      Questionnaire results were reviewed in workshops, analysing how differences
      between national laws might support or hinder regional responses to pandemic
      influenza. Respondents examined the impact of national laws on the movements of
      information, goods, services and people across borders in a time of pandemic, the
      capacity for surveillance, case detection, case management and community control,
      the deployment of strategies of prevention, containment, mitigation and recovery
      and the identification of commonalities and disconnects across states. RESULTS:
      Results of this study show differences across Europe in the extent to which
      national pandemic policy and pandemic plans have been integrated with public
      health laws. We found significant differences in legislation and in the
      legitimacy of strategic plans. States differ in the range and the nature of
      intervention measures authorized by law, the extent to which borders could be
      closed to movement of persons and goods during a pandemic, and access to
      healthcare of non-resident persons. Some states propose use of emergency powers
      that might potentially override human rights protections while other states
      propose to limit interventions to those authorized by public health laws.
      CONCLUSION: These differences could create problems for European strategies if an
      evolving influenza pandemic results in more serious public health challenges or,
      indeed, if a novel disease other than influenza emerges with pandemic potential.
      There is insufficient understanding across Europe of the role and importance of
      law in pandemic planning. States need to build capacity in public health law to
      support disease prevention and control policies. Our research suggests that
      states would welcome further guidance from the EU on management of a pandemic,
      and guidance to assist in greater commonality of legal approaches across states.

PMID- 20815889
TI  - Prevalence of primary biliary cirrhosis in adults referring hospital for annual
      health check-up in Southern China.
AB  - BACKGROUND: Primary biliary cirrhosis (PBC) is an autoimmune liver disease
      characterized by the presence of anti-mitocondrial autoantibodies (AMA) which has
      an essential role also for diagnosis. In addition, also some anti-nuclear
      antibodies (ANA) have been shown to be highly specific PBC. The purpose of this
      study was to assess the prevalence of PBC among the adults referring hospital for
      annual health check-up in Southern China by screening sera for PBC-specific
      autoantibodies. METHODS: AMA and ANA were screened in 8,126 adults (mean age 44
      +/- 15 years, 48% females) by indirect immunofluorenscence (IIF). Positive sera
      were tested by ELISA/immunoblotting for AMA-M2, anti-sp100 and anti-gp210. A
      diagnosis of PBC was re-assessed six months after the initial testing. RESULTS:
      Out of 8,126 individuals 35 were positive for AMA and 79 positive for ANA.
      Nineteen, 4, and 3 of the subjects positive for AMA and/or ANA showed reactivity
      for AMA-M2, anti-sp100 or gp210, respectively, further tested with
      ELISA/immunoblotting. Fourteen in the 39 individuals positive for AMA at IIF, AMA
      M2, anti-gp210, or anti-sp100 had abnormal cholestatic liver functional indices.
      One definite and 3 probable PBC diagnosis could be made in 4 cases including 3
      females and 1 male after half a year. CONCLUSIONS: We found a point prevalence
      rate of PBC among Southern Chinese adults attending for yearly health check-up of
      492 cases per million (95% CI, 128 to 1,093) and 1,558 cases per million (95% CI,
      294 to 3,815) for women over 40, a finding similar to prevalence reported in
      other geographical areas.

PMID- 20815890
TI  - Comparison of the efficacy of lamivudine and telbivudine in the treatment of
      chronic hepatitis B: a systematic review.
AB  - BACKGROUND: Chronic viral hepatitis B remains a global public health concern.
      Currently, several drugs, such as lamivudine and telbivudine, are recommended for
      treatment of patients with chronic hepatitis B. However, there are no conclusive
      results on the comparison of the efficacy of lamivudine (LAM) and telbivudine
      (LdT) in the treatment of chronic hepatitis B. RESULTS: To evaluate the
      comparison of the efficacy of LAM and LdT in the treatment of chronic hepatitis B
      by a systematic review and meta-analysis of clinical trials, we searched PUBMED
      (from 1990 to April 2010), Web of Science (from 1990 to April 2010), EMBASE (from
      1990 to April 2010), CNKI (National Knowledge Infrastructure) (from 1990 to April
      2010), VIP database (from 1990 to April 2010), WANFANG database (from 1990 to
      April 2010), the Cochrane Central Register of Controlled Trials and the Cochrane
      Database of Systematic Review. At the end of one-year treatment, LdT was better
      than LAM at the biochemical response, virological response, HBeAg loss,
      therapeutic response, while less than at the viral breakthrough and viral
      resistance, but there was no significant difference in the HBeAg seroconversion
      and HBsAg response. LdT was better than LAM at the HBeAg seroconversion with
      prolonged treatment to two years. CONCLUSIONS: In summary, LdT was superior in
      inhibiting HBV replication and preventing drug resistance as compared to LAM for
      CHB patients. But LdT may cause more nonspecific adverse events and can lead to
      more CK elevation than LAM. It is thus recommended that the LdT could be used as
      an option for patients but adverse events, for example CK elevation, must be
      monitored.

PMID- 20815891
TI  - Relations of self-regulation and self-efficacy for exercise and eating and BMI
      change: A field investigation.
AB  - OBJECTIVES: This study aimed to assess relations of self-regulatory skill use
      with self-efficacy for exercise and appropriate eating, and the resulting change
      in weight associated with participation in a nutrition and exercise treatment
      supported by cognitive-behavioral methods. METHODS: Adults with severe obesity (N
      = 95; mean BMI = 40.5 +/- 3.9 kg/m2) participated in a 6-month exercise and
      nutrition treatment emphasizing self-regulatory skills. Changes in self
      regulatory skills usage, self-efficacy, overall mood, and BMI were measured.
      Relations of changes in self-regulatory skill use and self-efficacy, for both
      physical activity and appropriate eating, were assessed, as was the possibility
      of mood change being a mediator of these relationships. Indirect effects of the
      variables associated with the present treatment on BMI change were then
      estimated. RESULTS: For both exercise and appropriate eating, changes in self
      regulation were associated with self-efficacy change. Mood change partially
      mediated the relationship between changes in self-regulation for appropriate
      eating and self-efficacy for appropriate eating. Self-efficacy changes for
      physical activity and controlled eating, together, explained a significant
      portion of the variance in BMI change (R2 = 0.26, p < 0.001). The total indirect
      effect of the treatment on BMI change was 0.20. CONCLUSION: Findings suggest that
      training in self-regulation for exercise and eating may benefit self-efficacy and
      weight-loss outcomes. Thus, these variables should be considered in both the
      theory and behavioral treatment of obesity.

PMID- 20815892
TI  - Gene expression model (in)validation by Fourier analysis.
AB  - BACKGROUND: The determination of the right model structure describing a gene
      regulation network and the identification of its parameters are major goals in
      systems biology. The task is often hampered by the lack of relevant experimental
      data with sufficiently low noise level, but the subset of genes whose
      concentration levels exhibit an oscillatory behavior in time can readily be
      analyzed on the basis of their Fourier spectrum, known to turn complex signals
      into few relatively noise-free parameters. Such genes therefore offer
      opportunities of understanding gene regulation quantitatively. RESULTS: Fourier
      analysis is applied to data on gene expression levels in mouse liver cells that
      oscillate according to the circadian rhythm. Several model structures in the form
      of linear and nonlinear differential equations are matched to the data and it is
      shown that although the considered models can reproduce many features of the
      oscillatory patterns, some can be excluded on the basis of Fourier analysis
      without appeal to prior knowledge of regulatory pathways. A systematic method for
      testing models is also proposed based on measuring the effects of variations in
      gene copy-number on the expression levels of coupled genes. CONCLUSIONS: Fourier
      analysis is a technique that is well-adapted to the study of biological
      oscillators and can be used instead or in addition to conventional modeling
      techniques. Its usefulness will increase as more high-resolution data become
      available.

PMID- 20815893
TI  - Inhibitory effects on HAV IRES-mediated translation and replication by a
      combination of amantadine and interferon-alpha.
AB  - Hepatitis A virus (HAV) causes acute hepatitis and sometimes leads to fulminant
      hepatitis. Amantadine is a tricyclic symmetric amine that inhibits the
      replication of many DNA and RNA viruses. Amantadine was reported to suppress HAV
      replication, and the efficacy of amantadine was exhibited in its inhibition of
      the internal ribosomal entry site (IRES) activities of HAV. Interferon (IFN) also
      has an antiviral effect through the induction of IFN stimulated genes (ISG) and
      the degradation of viral RNA. To explore the mechanism of the suppression of HAV
      replication, we examined the effects of the combination of amantadine and IFN
      alpha on HAV IRES-mediated translation, HAV replicon replication in human
      hepatoma cell lines, and HAV KRM003 genotype IIIB strain replication in African
      green monkey kidney cell GL37. IFN-alpha seems to have no additive effect on HAV
      IRES-mediated translation inhibition by amantadine. However, suppressions of HAV
      replicon and HAV replication were stronger with the combination than with
      amantadine alone. In conclusion, amantadine, in combination of IFN-alpha, might
      have a beneficial effect in some patients with acute hepatitis A.

PMID- 20815894
TI  - Potential therapeutic strategy for non-Hodgkin lymphoma by anti
      CD20scFvFc/CD28/CD3zeta gene tranfected T cells.
AB  - BACKGROUND: Anti-CD20 monoclonal antibody treatment has not only increased
      survival and cure rates in many non-Hodgkin lymphomas, but also has prompted an
      explosion in the development of novel antibodies and biologically active
      substances with specific cellular targets in the field of malignancies treatment.
      Since the robust immune responses are elicited by the gene-modified T cells, gene
      based T cell therapy may also provide a powerful tool for cancer immunotherapy.
      METHODS: In this study, we developed a vector construction encoding a chimeric T
      cell receptor that recognizes the CD20 antigen and delivers co-stimulatory
      signals to achieve T cell activation. One non-Hodgkin lymphoma cell line Raji
      cells co-cultured with peripheral blood-derived T cells were stably transfected
      with anti-CD20scFvFc/CD28/CD3zeta gene or anti-CD20scFvFc gene. T cells
      expressing anti-CD20scFvFc/CD28/CD3zeta or anti-CD20scFvFc gene co-cultured with
      CD20 positive Raji cells for different times. Cell lysis assay was carried by
      [3H]TdR release assay. The expressions of Fas, Bcl-2 and Caspase-3 of Raji cells
      were detected by flow cytometric. The secretion of IFN-gamma and IL-2 in co
      culture medium was tested by ELISA assay. Activity of AP-1 was analyzed by EMSA.
      RESULTS: Following efficient transduction of peripheral blood-derived T cells
      with anti-CD20scFvFc/CD28/CD3zeta gene, an obvious cell lysis of Raji cells was
      observed in co-culture. T cells transduced anti-CD20scFvFc/CD28/CD3zeta gene had
      superior secretion of IFN-gamma and IL-2 compared to T cells transduced anti
      CD20scFvFc gene. Also it led to a much stronger Fas-induced apoptosis signaling
      transduction in target cancer cells. CONCLUSION: So adoptively T cells transduced
      anti-CD20scFvFc/CD28/CD3zeta gene mediates enhanced anti-tumor activities against
      CD20 positive tumor cells, suggesting a potential of gene-based immunotherapy for
      non-Hodgkin lymphoma.

PMID- 20815895
TI  - Bioaccessibility, bioavailability and toxicity of commercially relevant iron- and
      chromium-based particles: in vitro studies with an inhalation perspective.
AB  - BACKGROUND: Production of ferrochromium alloys (FeCr), master alloys for
      stainless steel manufacture, involves casting and crushing processes where
      particles inevitably become airborne and potentially inhaled. The aim of this
      study was to assess potential health hazards induced by inhalation of different
      well-characterized iron- and chromium-based particles, i.e. ferrochromium (FeCr),
      ferrosiliconchromium (FeSiCr), stainless steel (316L), iron (Fe), chromium (Cr),
      and chromium(III)oxide (Cr2O3), in different size fractions using in vitro
      methods. This was done by assessing the extent and speciation of released metals
      in synthetic biological medium and by analyzing particle reactivity and toxicity
      towards cultured human lung cells (A549). RESULTS: The amount of released metals
      normalized to the particle surface area increased with decreasing particle size
      for all alloy particles, whereas the opposite situation was valid for particles
      of the pure metals. These effects were evident in artificial lysosomal fluid
      (ALF) of pH 4.5 containing complexing agents, but not in neutral or weakly
      alkaline biological media. Chromium, iron and nickel were released to very low
      extent from all alloy particles, and from particles of Cr due to the presence of
      a Cr(III)-rich protective surface oxide. Released elements were neither
      proportional to the bulk nor to the surface composition after the investigated
      168 hours of exposure. Due to a surface oxide with less protective properties,
      significantly more iron was released from pure iron particles compared with the
      alloys. Cr was predominantly released as Cr(III) from all particles investigated
      and was strongly complexed by organic species of ALF. Cr2O3 particles showed
      hemolytic activity, but none of the alloy particles did. Fine-sized particles of
      stainless steel caused however DNA damage, measured with the comet assay after 4
      h exposure. None of the particles revealed any significant cytotoxicity in terms
      of cell death after 24 h exposure. CONCLUSION: It is evident that particle and
      alloy characteristics such as particle size and surface composition are important
      aspects to consider when assessing particle toxicity and metal release from alloy
      particles compared to pure metal particles. Generated results clearly elucidate
      that neither the low released concentrations of metals primarily as a result of
      protective and poorly soluble surface oxides, nor non-bioavailable chromium
      complexes, nor the particles themselves of occupational relevance induced
      significant acute toxic response, with exception of DNA damage from stainless
      steel.

PMID- 20815896
TI  - Wound contraction effects and antibacterial properties of Tualang honey on full
      thickness burn wounds in rats in comparison to hydrofibre.
AB  - BACKGROUND: Full-thickness burn wounds require excision and skin grafting.
      Multiple surgical procedures are inevitable in managing moderate to severe full
      thickness burns. Wound bed preparations prior to surgery are necessary in order
      to prevent wound infection and promote wound healing. Honey can be used to treat
      burn wounds. However, not all the honey is the same. This study aims to evaluate
      the wound contraction and antibacterial properties of locally-produced Tualang
      honey on managing full-thickness burn wounds in vivo. METHODS: Thirty-six female
      Sprague Dawley rats were randomly divided into three groups. Under anaesthesia,
      three full-thickness burn wounds were created on the dorsum of the rats. The full
      thickness burn wounds were inoculated with a specific organism (10(4)), namely
      Pseudomonas aeruginosa (n = 12), Klebsiella pneumoniae (n = 12), or Acinetobacter
      baumannii (n = 12). The three burn wounds were dressed with Tualang honey,
      hydrofibre and hydrofibre silver respectively. Swab samples were obtained every 3
      days (day 3, 6, 9, 12, 15, 18 and 21) for quantitative and semi-quantitative
      microbiological analyses. Clinical assessments, including observations concerning
      the appearance and wound size, were measured at the same time. RESULTS: There was
      a rapid 32.26% reduction in wound size by day 6 (p = 0.008) in the Tualang honey
      treated wounds, and 49.27% by day 15 (p = 0.005). The wounds remained smaller by
      day 18 (p < 0.032). Tualang honey-treated rats demonstrated a reduction in
      bacterial growth in Pseudomonas aeruginosa inoculated wounds (p = 0.005).
      However, hydrofibre silver and hydrofibre-treated wounds are superior to honey
      treated wounds with Acinetobacter baumannii (p = 0.035). There was no statistical
      significant of antibacterial property in Klebsiella pneumonia inoculated wounds.
      CONCLUSIONS: Tualang honey has better results with regards to its control of
      Pseudomonas aeruginosa and its wound contraction effects on full-thickness burn
      wound in vivo.

PMID- 20815897
TI  - Effect of hemodialysis and peritoneal dialysis on redox status in chronic renal
      failure patients: a comparative study.
AB  - OBJECTIVE: To investigate the effects of hemodialysis (HD) and periotoneal
      dialysis (PD) on oxidative stress in chronic renal failure patients (CRF).
      METHODS: 20 HD patients (M/F: 8/12, 36 +/- 12 years) and 20 PD patients (M/F:
      10/10, 40 +/- 8 years) were compared with 20 end stage renal failure patients
      (CRF) (M/F: 4/16, 61 +/- 13 years). RESULTS: Thiobarbituric acid reactive
      substances (TBARS) values were elevated in HD and decreased in PD compared to CRF
      (P < 0.05). TBARS-VLDL and TBARS-HDL2 were decreased in HD and PD, compared to
      CRF (p < 0.05). TBARS-LDL were higher in HD compared to CRF (p < 0.05). No
      significant difference in TBARS-HDL3 values between the three groups. Carbonyls
      were increased in HD (p < 0.05) and PD (p < 0.01) compared to CRF. Plasma
      superoxide dismutase activity (SOD) was decreased in HD compared to CRF and PD (P
      < 0.05). Glutathion peroxidase activity (GSH-Px) was decreased in HD and PD (P <
      0.005), compared to CRF. Decrease in catalase activity was noted only in PD
      compared to CRF (P < 0.05). An increase in nitric oxide was noted in HD compared
      to CRF (p < 0.05). Albumin concentrations were higher in HD and PD compared to
      CRF (P < 0.001). Whereas uric acid concentrations were decreased in HD (P <
      0.001) compared to CRF and PD. Bilirubin values were similar in all groups.
      Increased values of iron were noted in HD and PD, compared to PD (p < 0.001).
      CONCLUSION: HD and PD aggravate oxidative stress generated by uremia. HD
      accentuates lipid and protein peroxidation, while PD aggravates protein
      oxidation. However, the activity of antioxidant enzymes was altered by both
      dialysis treatments.

PMID- 20815898
TI  - Nasal continuous positive airway pressure improves myocardial perfusion reserve
      and endothelial-dependent vasodilation in patients with obstructive sleep apnea.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) has been associated with cardiovascular
      disease (CVD), but whether OSA is an independent risk factor for CVD is
      controversial. The purpose of this study is to determine if patients with OSA
      have subclinical cardiovascular disease that is detectable by multi-modality
      cardiovascular imaging and whether these abnormalities improve after nasal
      continuous positive airway pressure (nCPAP). RESULTS: Of the 35 consecutive
      subjects with newly diagnosed moderate to severe OSA recruited from the Stanford
      Sleep Disorders Clinic, 20 patients were randomized to active vs. sham nCPAP.
      Active nCPAP was titrated to pressures that would prevent sleep disordered
      breathing based on inpatient polysomnography. OSA patients had baseline vascular
      function abnormalities including decreased myocardial perfusion reserve (MPR),
      brachial flow mediated dilation (FMD) and nitroglycerin-induced coronary
      vasodilation. Patients randomized to active nCPAP had improvement of MPR (1.5 +/-
      0.5 vs. 3.0 +/- 1.3, p = 0.02) and brachial FMD (2.5% +/- 5.7% vs. 9.0% +/- 6.5%,
      p = 0.03) after treatment, but those randomized to sham nCPAP showed no
      significant improvement. There were no significant changes seen in chamber sizes,
      systolic and diastolic function, valvular function and coronary vasodilation to
      nitroglycerin. CONCLUSIONS: Patients with moderate to severe OSA had decreased
      MPR and brachial FMD that improved after 3 months of nCPAP. These findings
      suggest that relief of apnea in OSA may improve microvascular disease and
      endothelial dysfunction, which may prevent the development of overt
      cardiovascular disease. Further study in a larger patient population may be
      warranted.

PMID- 20815899
TI  - Dietary and physical activity adaptations to alternate day modified fasting:
      implications for optimal weight loss.
AB  - BACKGROUND: Alternate day modified fasting (ADMF) is an effective strategy for
      weight loss in obese adults. OBJECTIVE: The objective of this study was to
      examine the dietary and physical activity adaptations that occur during short
      term ADMF, and to determine how these modulations affect rate of weight loss.
      METHODS: Sixteen obese subjects (12 women/4 men) completed a 10-week trial
      consisting of 3 phases: 1) 2-week control phase, 2) 4-week ADMF controlled
      feeding phase, and 3) 4-week ADMF self-selected feeding phase. RESULTS: Body
      weight decreased (P < 0.001) by 5.6 +/- 1.0 kg post-treatment. Energy intake on
      the fast day was 26 +/- 3% of baseline needs (501 +/- 28 kcal/d). No hyperphagic
      response occurred on the feed day (95 +/- 6% of baseline needs consumed, 1801 +/-
      226 kcal/d). Daily energy restriction (37 +/- 7%) was correlated to rate of
      weight loss (r = 0.42, P = 0.01). Dietary fat intake decreased (36% to 33% of
      kcal, P < 0.05) with dietary counseling, and was related to rate of weight loss
      (r = 0.38, P = 0.03). Hunger on the fast day decreased (P < 0.05) by week 2, and
      remained low. Habitual physical activity was maintained throughout the study
      (fast day: 6416 +/- 851 steps/d; feed day: 6569 +/- 910 steps/d). CONCLUSION:
      These findings indicate that obese subjects quickly adapt to ADMF, and that
      changes in energy/macronutrient intake, hunger, and maintenance of physical
      activity play a role in influencing rate of weight loss by ADMF.

PMID- 20815900
TI  - Economic evaluation of pneumococcal conjugate vaccination in The Gambia.
AB  - BACKGROUND: Gambia is the second GAVI support-eligible country to introduce the 7
      valent pneumococcal conjugate vaccine (PCV7), but a country-specific cost
      effectiveness analysis of the vaccine is not available. Our objective was to
      assess the potential impact of PCVs of different valences in The Gambia. METHODS:
      We synthesized the best available epidemiological and cost data using a state
      transition model to simulate the natural histories of various pneumococcal
      diseases. For the base-case, we estimated incremental cost (in 2005 US dollars)
      per disability-adjusted life year (DALY) averted under routine vaccination using
      PCV9 compared to no vaccination. We extended the base-case results for PCV9 to
      estimate the cost-effectiveness of PCV7, PCV10, and PCV13, each compared to no
      vaccination. To explore parameter uncertainty, we performed both deterministic
      and probabilistic sensitivity analyses. We also explored the impact of vaccine
      efficacy waning, herd immunity, and serotype replacement, as a part of the
      uncertainty analyses, by assuming alternative scenarios and extrapolating
      empirical results from different settings. RESULTS: Assuming 90% coverage, a
      program using a 9-valent PCV (PCV9) would prevent approximately 630
      hospitalizations, 40 deaths, and 1000 DALYs, over the first 5 years of life of a
      birth cohort. Under base-case assumptions ($3.5 per vaccine), compared to no
      intervention, a PCV9 vaccination program would cost $670 per DALY averted in The
      Gambia. The corresponding values for PCV7, PCV10, and PCV13 were $910, $670, and
      $570 per DALY averted, respectively. Sensitivity analyses that explored the
      implications of the uncertain key parameters showed that model outcomes were most
      sensitive to vaccine price per dose, discount rate, case-fatality rate of primary
      endpoint pneumonia, and vaccine efficacy against primary endpoint pneumonia.
      CONCLUSIONS: Based on the information available now, infant PCV vaccination would
      be expected to reduce pneumococcal diseases caused by S. pneumoniae in The
      Gambia. Assuming a cost-effectiveness threshold of three times GDP per capita,
      all PCVs examined would be cost-effective at the tentative Advance Market
      Commitment (AMC) price of $3.5 per dose. Because the cost-effectiveness of a PCV
      program could be affected by potential serotype replacement or herd immunity
      effects that may not be known until after a large scale introduction, type
      specific surveillance and iterative evaluation will be critical.

PMID- 20815901
TI  - Large-scale proteomic identification of S100 proteins in breast cancer tissues.
AB  - BACKGROUND: Attempts to reduce morbidity and mortality in breast cancer is based
      on efforts to identify novel biomarkers to support prognosis and therapeutic
      choices. The present study has focussed on S100 proteins as a potentially
      promising group of markers in cancer development and progression. One reason of
      interest in this family of proteins is because the majority of the S100 genes are
      clustered on a region of human chromosome 1q21 that is prone to genomic
      rearrangements. Moreover, there is increasing evidence that S100 proteins are
      often up-regulated in many cancers, including breast, and this is frequently
      associated with tumour progression. METHODS: Samples of breast cancer tissues
      were obtained during surgical intervention, according to the bioethical
      recommendations, and cryo-preserved until used. Tissue extracts were submitted to
      proteomic preparations for 2D-IPG. Protein identification was performed by N
      terminal sequencing and/or peptide mass finger printing. RESULTS: The majority of
      the detected S100 proteins were absent, or present at very low levels, in the non
      tumoral tissues adjacent to the primary tumor. This finding strengthens the role
      of S100 proteins as putative biomarkers. The proteomic screening of 100 cryo
      preserved breast cancer tissues showed that some proteins were ubiquitously
      expressed in almost all patients while others appeared more sporadic. Most, if
      not all, of the detected S100 members appeared reciprocally correlated. Finally,
      from the perspective of biomarkers establishment, a promising finding was the
      observation that patients which developed distant metastases after a three year
      follow-up showed a general tendency of higher S100 protein expression, compared
      to the disease-free group. CONCLUSIONS: This article reports for the first time
      the comparative proteomic screening of several S100 protein members among a large
      group of breast cancer patients. The results obtained strongly support the
      hypothesis that a significant deregulation of multiple S100 protein members is
      associated with breast cancer progression, and suggest that these proteins might
      act as potential prognostic factors for patient stratification. We propose that
      this may offer a significant contribution to the knowledge and clinical
      applications of the S100 protein family to breast cancer.

PMID- 20815902
TI  - Expression of CIAPIN1 in human colorectal cancer and its correlation with
      prognosis.
AB  - BACKGROUND: The cytokine-induced anti-apoptotic molecule (CIAPIN1) had been found
      to be a differentially-expressed gene involved in a variety of cancers, and it
      was also considered as a candidate tumour suppressor gene in gastric cancer,
      renal cancer and liver cancer. However, studies on the role of CIAPIN1 in
      colorectal cancer were still unavailable. The aim of this study was to determine
      the prognostic impact of CIAPIN1 in 273 colorectal cancer (CRC) samples and to
      investigate the CIAPIN1 expression in CRC cell lines after inducing
      differentiation. METHODS: Immunohistochemical analysis was performed to detect
      the expression of CIAPIN1 in CRC samples from 273 patients. The relationship
      between CIAPIN1 expression and patients' characteristics (gender, age, location
      of cancer, UICC stage, local recurrence and tumour grade factors) was evaluated.
      In addition, these patients were followed up for five consecutive years to
      investigate the relationship between CIAPIN1 expression and the prognosis of CRC.
      We induced the differentiation of the CRC cell lines HT29 and SW480, in order to
      detect the expression of CIAPIN1 in the process of CRC cells differentiation.
      RESULTS: Results indicated that CIAPIN1 was mainly expressed in the cytoplasm and
      nucleus, and that its expression level in cancer samples was significantly lower
      than in normal tissues. The Wilcoxon-Mann-Whitney test showed a significant
      difference in the differential expression of CIAPIN1 in patients with different T
      and UICC stages, and tumour grade (P = 0.0393, 0.0297 and 0.0397, respectively).
      The Kaplan-Meier survival analysis demonstrated that the survival time of CRC
      patients with high expression of CIAPIN1 was longer than those with low
      expression during the 5-year follow up period (P = 0.0002). COX regression
      analysis indicated that low expression of CIAPIN1, cancer stage of > pT1, distant
      organ metastasis (pM1), regional lymph node metastasis (> pN1) and local
      recurrence (yes) were independent, poor prognostic factors of CRC (P = 0.012, P =
      0.032, P <0.001, P <0.001, P <0.001 respectively). Both Western blotting and RT
      PCR showed that CIAPIN1 expression was increased with the degree of
      differentiation of HT29 and SW480 cells. CONCLUSIONS: CIAPIN1 played an important
      role in the differentiation of CRC cells, and the differential expression of
      CIAPIN1 in CRC was closely related to prognosis.

PMID- 20815903
TI  - The chondrogenic response to exercise in the proximal femur of normal and mdx
      mice.
AB  - BACKGROUND: Submaximal exercise is used in the management of muscular dystrophy.
      The effects of mechanical stimulation on skeletal development are well
      understood, although its effects on cartilage growth have yet to be investigated
      in the dystrophic condition. The objective of this study was to investigate the
      chondrogenic response to voluntary exercise in dystrophin-deficient mice.
      METHODS: Control and dystrophin-deficient (mdx) mice were divided into sedentary
      and exercise-treated groups and tested for chondral histomorphometric differences
      at the proximal femur. RESULTS: Control mice ran 7 km/week further than mdx mice
      on average, but this difference was not statistically significant (P > 0.05).
      However, exercised control mice exhibited significantly enlarged femur head
      diameter, articular cartilage thickness, articular cartilage tissue area, and
      area of calcified cartilage relative to sedentary controls and exercised mdx mice
      (P < 0.05). No differences were found between other treatment groups.
      CONCLUSIONS: Mdx mice exhibit a reduced chondrogenic response to increased
      mechanical stimulation relative to controls. However, no significant reduction in
      articular dimensions was found, indicating loss of chondral tissue may not be a
      clinical concern with dystrophinopathy.

PMID- 20815904
TI  - Coordination of glioblastoma cell motility by PKCiota.
AB  - BACKGROUND: Glioblastoma is one of the deadliest forms of cancer, in part because
      of its highly invasive nature. The tumor suppressor PTEN is frequently mutated in
      glioblastoma and is known to contribute to the invasive phenotype. However the
      downstream events that promote invasion are not fully understood. PTEN loss leads
      to activation of the atypical protein kinase C, PKCiota. We have previously shown
      that PKCiota is required for glioblastoma cell invasion, primarily by enhancing
      cell motility. Here we have used time-lapse videomicroscopy to more precisely
      define the role of PKCiota in glioblastoma. RESULTS: Glioblastoma cells in which
      PKCiota was either depleted by shRNA or inhibited pharmacologically were unable
      to coordinate the formation of a single leading edge lamellipod. Instead, some
      cells generated multiple small, short-lived protrusions while others generated a
      diffuse leading edge that formed around the entire circumference of the cell.
      Confocal microscopy showed that this behavior was associated with altered
      behavior of the cytoskeletal protein Lgl, which is known to be inactivated by
      PKCiota phosphorylation. Lgl in control cells localized to the lamellipod leading
      edge and did not associate with its binding partner non-muscle myosin II,
      consistent with it being in an inactive state. In PKCiota-depleted cells, Lgl was
      concentrated at multiple sites at the periphery of the cell and remained in
      association with non-muscle myosin II. Videomicroscopy also identified a novel
      role for PKCiota in the cell cycle. Cells in which PKCiota was either depleted by
      shRNA or inhibited pharmacologically entered mitosis normally, but showed marked
      delays in completing mitosis. CONCLUSIONS: PKCiota promotes glioblastoma motility
      by coordinating the formation of a single leading edge lamellipod and has a role
      in remodeling the cytoskeleton at the lamellipod leading edge, promoting the
      dissociation of Lgl from non-muscle myosin II. In addition PKCiota is required
      for the transition of glioblastoma cells through mitosis. PKCiota therefore has a
      role in both glioblastoma invasion and proliferation, two key aspects in the
      malignant nature of this disease.

PMID- 20815905
TI  - Quantification of vestibular-induced eye movements in zebrafish larvae.
AB  - BACKGROUND: Vestibular reflexes coordinate movements or sensory input with
      changes in body or head position. Vestibular-evoked responses that involve the
      extraocular muscles include the vestibulo-ocular reflex (VOR), a compensatory eye
      movement to stabilize retinal images. Although an angular VOR attributable to
      semicircular canal stimulation was reported to be absent in free-swimming
      zebrafish larvae, recent studies reveal that vestibular-induced eye movements can
      be evoked in zebrafish larvae by both static tilts and dynamic rotations that
      tilt the head with respect to gravity. RESULTS: We have determined herein the
      basis of sensitivity of the larval eye movements with respect to vestibular
      stimulus, developmental stage, and sensory receptors of the inner ear. For our
      experiments, video recordings of larvae rotated sinusoidally at 0.25 Hz were
      analyzed to quantitate eye movements under infrared illumination. We observed a
      robust response that appeared as early as 72 hours post fertilization (hpf),
      which increased in amplitude over time. Unlike rotation about an earth horizontal
      axis, rotation about an earth vertical axis at 0.25 Hz did not evoke eye
      movements. Moreover, vestibular-induced responses were absent in mutant cdh23
      larvae and larvae lacking anterior otoliths. CONCLUSIONS: Our results provide
      evidence for a functional vestibulo-oculomotor circuit in 72 hpf zebrafish larvae
      that relies upon sensory input from anterior/utricular otolith organs.

PMID- 20815906
TI  - Revisiting Lynam's notion of the "fledgling psychopath": are HIA-CP children
      truly psychopathic-like?
AB  - BACKGROUND: In his developmental model of emerging psychopathy, Lynam proposed
      that the "fledgling psychopath" is most likely to be located within a subgroup of
      children elevated in both hyperactivity/inattention/impulsivity (HIA) and conduct
      problems (CP). This approach has garnered some empirical support. However, the
      extent to which Lynam's model captures children who resemble psychopathy with
      regard to the core affective and interpersonal features remains unclear. METHODS:
      In the present study, we investigated this issue within a large community sample
      of youth (N = 617). Four groups (non-HIA-CP, HIA-only, CP-only, and HIA-CP),
      defined on the basis of teacher reports of the Strengths and Difficulties
      Questionnaire (SDQ), were compared with respect to parent-reported psychopathic
      like traits and subjective emotional reactivity in response to unpleasant,
      emotionally-laden pictures from the International Affective Pictures System
      (IAPS). RESULTS: Results did not support Lynam's model. HIA-CP children did not
      appear most psychopathic-like on dimensions of callous-unemotional and
      narcissistic personality, nor did they report reduced emotional reactivity to the
      IAPS relative to the other children. Post-hoc regression analyses revealed a
      significant moderation such that elevated HIA weakened the association between CP
      and emotional underarousal. CONCLUSIONS: Implications of these findings with
      regard to the development of psychopathy are discussed.

PMID- 20815907
TI  - Effect of a 21 day Daniel Fast on metabolic and cardiovascular disease risk
      factors in men and women.
AB  - BACKGROUND: Dietary modification via caloric restriction is associated with
      multiple effects related to improved metabolic and cardiovascular health.
      However, a mandated reduction in kilocalories is not well-tolerated by many
      individuals, limiting the long-term application of such a plan. The Daniel Fast
      is a widely utilized fast based on the Biblical book of Daniel. It involves a 21
      day ad libitum food intake period, devoid of animal products and preservatives,
      and inclusive of fruits, vegetables, whole grains, legumes, nuts, and seeds. The
      purpose of the present study was to determine the efficacy of the Daniel Fast to
      improve markers of metabolic and cardiovascular disease risk. METHODS: 43
      subjects (13 men; 30 women; 35 +/- 1 yrs; range: 20-62 yrs) completed a 21 day
      period of modified food intake in accordance with detailed guidelines provided by
      investigators. All subjects purchased and prepared their own food. Following
      initial screening, subjects were given one week to prepare for the fast, after
      which time they reported to the lab for their pre-intervention assessment (day
      1). After the 21 day fast, subjects reported to the lab for their post
      intervention assessment (day 22). For both visits, subjects reported in a 12 hr
      fasted state, performing no strenuous physical activity during the preceding 24
      48 hrs. At each visit, mental and physical health (SF-12 form), resting heart
      rate and blood pressure, and anthropometric variables were measured. Blood was
      collected for determination of complete blood count, metabolic panel, lipid
      panel, insulin, HOMA-IR, and C-reactive protein (CRP). Subjects' self-reported
      compliance, mood, and satiety in relation to the fast were also recorded. Diet
      records were maintained by all subjects during the 7 day period immediately prior
      to the fast (usual intake) and during the final 7 days of the fast. RESULTS:
      Subjects' compliance to the fast was 98.7 +/- 0.2% (mean +/- SEM). Using a 10
      point scale, subjects' mood and satiety were both 7.9 +/- 0.2. The following
      variables were significantly (p < 0.05) lower following the fast as compared to
      before the fast: white blood cell count (5.68 +/- 0.24 vs. 4.99 +/- 0.19 103.MUL
      1), blood urea nitrogen (13.07 +/- 0.58 vs. 10.14 +/- 0.59 mg.dL-1), blood urea
      nitrogen/creatinine (14.74 +/- 0.59 vs. 11.67 +/- 0.68), protein (6.95 +/- 0.07
      vs. 6.77 +/- 0.06 g.dL-1), total cholesterol (171.07 +/- 4.57 vs. 138.69 +/- 4.39
      mg.dL-1), LDL-C (98.38 +/- 3.89 vs. 76.07 +/- 3.53 mg.dL-1), HDL-C (55.65 +/-
      2.50 vs. 47.58 +/- 2.19 mg.dL-1), SBP (114.65 +/- 2.34 vs. 105.93 +/- 2.12 mmHg),
      and DBP (72.23 +/- 1.59 vs. 67.00 +/- 1.43 mmHg). Insulin (4.42 +/- 0.52 vs. 3.37
      +/- 0.35 MUU.mL-1; p = 0.10), HOMA-IR (0.97 +/- 0.13 vs.0.72 +/- 0.08; p = 0.10),
      and CRP (3.15 +/- 0.91 vs. 1.60 +/- 0.42 mg.L-1; p = 0.13), were lowered to a
      clinically meaningful, albeit statistically insignificant extent. No significant
      difference was noted for any anthropometric variable (p > 0.05). As expected,
      multiple differences in dietary intake were noted (p < 0.05), including a
      reduction in total kilocalorie intake (2185 +/- 94 vs. 1722 +/- 85). CONCLUSION:
      A 21 day period of modified dietary intake in accordance with the Daniel Fast is
      1) well-tolerated by men and women and 2) improves several risk factors for
      metabolic and cardiovascular disease. Larger scale, randomized studies, inclusive
      of a longer time period and possibly a slight modification in food choice in an
      attempt to maintain HDL cholesterol, are needed to extend these findings.

PMID- 20815908
TI  - "Done more for me in a fortnight than anybody done in all me life." How welfare
      rights advice can help people with cancer.
AB  - BACKGROUND: In the UK many people with cancer and their carers do not have easy
      access to the welfare benefits to which they are entitled adding further strain
      to the process of dealing with cancer. It is estimated that nine out of ten
      cancer patients' households experience loss of income as a direct result of
      cancer, which, due to its socio-economic patterning disproportionately affects
      those most likely to be financially disadvantaged. In the UK proactive welfare
      rights advice services accessed via health care settings significantly increase
      benefit entitlement among people with health problems and this paper reports on a
      qualitative study examining the impact of a welfare rights advice service
      specifically designed for people affected by cancer and their carers in County
      Durham, North East England (UK). METHODS: Twenty two men and women with cancer or
      caring for someone with cancer who were recipients of welfare rights advice aged
      between 35 and 83 were recruited from a variety of health care and community
      settings. Semi-structured interviews were undertaken and analysed using the
      Framework method. RESULTS: Most of the participants experienced financial strain
      following their cancer diagnosis. Participants accessed the welfare rights
      service in a variety of ways, but mainly through referral by other professionals.
      The additional income generated by successful benefit claims was used in a number
      of ways and included offsetting additional costs associated with cancer and
      lessening the impact of loss of earnings. Overall, receiving welfare rights
      advice eased feelings of stress over financial issues at a time when participants
      were concerned about dealing with the impact of cancer. Lack of knowledge about
      benefit entitlements was the main barrier to accessing benefits, and this
      outweighed attitudinal factors such as stigma and concerns about benefit fraud.
      CONCLUSIONS: Financial strain resulting from a cancer diagnosis is compounded in
      the UK by lack of easy access to information about benefit entitlements and
      assistance to claim. Proactive welfare rights advice services, working closely
      with health and social care professionals can assist with the practical demands
      that arise from dealing with the illness and should be considered an important
      part of a holistic approach to cancer treatment.

PMID- 20815909
TI  - Sequential algorithm for life threatening cardiac pathologies detection based on
      mean signal strength and EMD functions.
AB  - BACKGROUND: Ventricular tachycardia (VT) and ventricular fibrillation (VF) are
      the most serious cardiac arrhythmias that require quick and accurate detection to
      save lives. Automated external defibrillators (AEDs) have been developed to
      recognize these severe cardiac arrhythmias using complex algorithms inside it and
      determine if an electric shock should in fact be delivered to reset the cardiac
      rhythm and restore spontaneous circulation. Improving AED safety and efficacy by
      devising new algorithms which can more accurately distinguish shockable from non
      shockable rhythms is a requirement of the present-day because of their uses in
      public places. METHOD: In this paper, we propose a sequential detection algorithm
      to separate these severe cardiac pathologies from other arrhythmias based on the
      mean absolute value of the signal, certain low-order intrinsic mode functions
      (IMFs) of the Empirical Mode Decomposition (EMD) analysis of the signal and a
      heart rate determination technique. First, we propose a direct waveform
      quantification based approach to separate VT plus VF from other arrhythmias. The
      quantification of the electrocardiographic waveforms is made by calculating the
      mean absolute value of the signal, called the mean signal strength. Then we use
      the IMFs, which have higher degree of similarity with the VF in comparison to VT,
      to separate VF from VTVF signals. At the last stage, a simple rate determination
      technique is used to calculate the heart rate of VT signals and the amplitude of
      the VF signals is measured to separate the coarse VF from VF. After these three
      stages of sequential detection procedure, we recognize the two components of
      shockable rhythms separately. RESULTS: The efficacy of the proposed algorithm has
      been verified and compared with other existing algorithms, e.g., HILB 1, PSR 2,
      SPEC 3, TCI 4, Count 5, using the MIT-BIH Arrhythmia Database, Creighton
      University Ventricular Tachyarrhythmia Database and MIT-BIH Malignant Ventricular
      Arrhythmia Database. Four quality parameters (e.g., sensitivity, specificity,
      positive predictivity, and accuracy) were calculated to ascertain the quality of
      the proposed and other comparing algorithms. Comparative results have been
      presented on the identification of VTVF, VF and shockable rhythms (VF + VT above
      180 bpm). CONCLUSIONS: The results show significantly improved performance of the
      proposed EMD-based novel method as compared to other reported techniques in
      detecting the life threatening cardiac arrhythmias from a set of large databases.

PMID- 20815910
TI  - On the threshold - evaluation of variability in effects of acupuncture in a
      gender perspective.
AB  - Variable results of pain alleviation in response to acupuncture have been
      reported, complicating its interpretation. Sources of variability are probably
      multi-factorial, including the contribution of gender related effects. Gender
      related variation in perceived pain has been discussed frequently, but documented
      effects of acupuncture referring to gender are sparse. Furthermore, factors such
      as operationalisation of the outcome variable and the statistical method for
      evaluation could also be sources of variability. When pain is regarded as
      subjective, the produced data should be treated as ordinal. The rank-based method
      by Svensson, taking the non-metric qualities of the ordinal data into account as
      well as the variability at the group and the individual level, is therefore an
      alternative. The present commentary aims to (1) evaluate changes in electrical
      sensory thresholds and electrical pain thresholds after low frequency electro
      acupuncture separately in healthy women and men; (2) introduce and exemplify the
      method by Svensson in a user-friendly approach. To analyze the systematic
      patterns of change in thresholds, indicating evidence of treatment on a group
      level, the relative position (RP) and relative concentration (RC), were measured.
      The variation related to the individual, the relative rank variation (RV) was
      also measured. The results were divergent between women (n = 23) and men (n =
      22), i.e. unchanged sensory threshold after acupuncture at the group level in
      women while changed in men. The assessed pain threshold after acupuncture on the
      other hand was changed towards higher levels in women and unchanged in men. The
      individual variation was apparent in both women and men but larger in women. For
      statistical analysis of the variability for both group and individual related
      effects, the rank-based method by Svensson could be used. The present study
      indicates that evaluation of sensory and pain threshold response should be
      analysed separately in women and men.

PMID- 20815911
TI  - Classification of videocapsule endoscopy image patterns: comparative analysis
      between patients with celiac disease and normal individuals.
AB  - BACKGROUND: Quantitative disease markers were developed to assess videocapsule
      images acquired from celiac disease patients with villous atrophy, and from
      control patients. METHOD: Capsule endoscopy videoclip images (576 x 576 pixels)
      were acquired at 2/second frame rate (11 celiacs, 10 controls) at regions: 1.
      bulb, 2. duodenum, 3. jejunum, 4. ileum and 5. distal ileum. Each of 200 images
      per videoclip (= 100s) were subdivided into 10 x 10 pixel subimages for which
      mean grayscale brightness level and its standard deviation (texture) were
      calculated. Pooled subimage values were grouped into low, intermediate, and high
      texture bands, and mean brightness, texture, and number of subimages in each band
      (nine features in all) were used for quantifying regions 1-5, and to determine
      the three best features for threshold and incremental learning classification.
      Classifiers were developed using 6 celiac and 5 control patients' data as
      exemplars, and tested on 5 celiacs and 5 controls. RESULTS: Pooled from all
      regions, the threshold classifier had 80% sensitivity and 96% specificity and the
      incremental classifier had 88% sensitivity and 80% specificity for predicting
      celiac versus control videoclips in the test set. Trends of increasing texture
      from regions 1 to 5 occurred in the low and high texture bands in celiacs, and
      the number of subimages in the low texture band diminished (r(2) > 0.5). No
      trends occurred in controls. CONCLUSIONS: Celiac videocapsule images have
      textural properties that vary linearly along the small intestine. Quantitative
      markers can assist in screening for celiac disease and localize extent and degree
      of pathology throughout the small intestine.

PMID- 20815912
TI  - Proposed follow up programme after curative resection for lower third oesophageal
      cancer.
AB  - The incidence of oesophageal adenocarcinoma has risen throughout the Western
      world over the last three decades. The prognosis remains poor as many patients
      are elderly and present with advanced disease. Those patients who are suitable
      for resection remain at high risk of disease recurrence. It is important that
      cancer patients take part in a follow up protocol to detect disease recurrence,
      offer psychological support, manage nutritional disorders and facilitate audit of
      surgical outcomes. Despite the recognition that regular postoperative follow up
      plays a key role in ongoing care of cancer patients, there is little consensus on
      the nature of the process. This paper reviews the published literature to
      determine the optimal timing and type of patient follow up for those after
      curative oesophageal resection.

PMID- 20815913
TI  - Eotaxin and FGF enhance signaling through an extracellular signal-related kinase
      (ERK)-dependent pathway in the pathogenesis of Eosinophilic esophagitis.
AB  - BACKGROUND: Eosinophilic esophagitis (EoE) is characterized by the inflammation
      of the esophagus and the infiltration of eosinophils into the esophagus, leading
      to symptoms such as dysphagia and stricture formation. Systemic immune indicators
      like eotaxin and fibroblast growth factor were evaluated for possible synergistic
      pathological effects. Moreover, blood cells, local tissue, and plasma from EoE
      and control subjects were studied to determine if the localized disease was
      associated with a systemic effect that correlated with presence of EoE disease.
      METHOD: Real-time polymerase chain reaction from peripheral blood mononuclear
      cells (PBMC), immunohistochemistry from local esophageal biopsies, fluid assays
      on plasma, and fluorescence-activated cell sorting on peripheral blood cells from
      subjects were used to study the systemic immune indicators in newly diagnosed EoE
      (n = 35), treated EoE (n = 9), Gastroesophageal reflux disease (GERD) (n = 8),
      ulcerative colitis (n = 5), Crohn's disease (n = 5), and healthy controls (n =
      8). RESULT: Of the transcripts tested for possible immune indicators, we found
      extracellular signal-regulated kinase (ERK), Bcl-2, bFGF (basic fibroblast growth
      factor), and eotaxin levels were highly upregulated in PBMC and associated with
      disease presence of EoE. Increased FGF detected by immunohistochemistry in
      esophageal tissues and in PBMC was correlated with low levels of pro-apoptotic
      factors (Fas, Caspase 8) in PBMC from EoE subjects. Plasma-derived bFGF was shown
      to be the most elevated and most specific in EoE subjects in comparison to
      healthy controls and disease control subjects. CONCLUSION: We describe for the
      first time a possible mechanism by which increased FGF is associated with
      inhibiting apoptosis in local esophageal tissues of EoE subjects as compared to
      controls. Eotaxin and FGF signaling pathways share activation through the ERK
      pathway; together, they could act to increase eosinophil activation and prolong
      the half-life of eosinophils in local tissues of the esophagus in EoE subjects.

PMID- 20815914
TI  - The use of 3D surface scanning for the measurement and assessment of the human
      foot.
AB  - BACKGROUND: A number of surface scanning systems with the ability to quickly and
      easily obtain 3D digital representations of the foot are now commercially
      available. This review aims to present a summary of the reported use of these
      technologies in footwear development, the design of customised orthotics, and
      investigations for other ergonomic purposes related to the foot. METHODS: The
      PubMed and ScienceDirect databases were searched. Reference lists and experts in
      the field were also consulted to identify additional articles. Studies in English
      which had 3D surface scanning of the foot as an integral element of their
      protocol were included in the review. RESULTS: Thirty-eight articles meeting the
      search criteria were included. Advantages and disadvantages of using 3D surface
      scanning systems are highlighted. A meta-analysis of studies using scanners to
      investigate the changes in foot dimensions during varying levels of weight
      bearing was carried out. CONCLUSIONS: Modern 3D surface scanning systems can
      obtain accurate and repeatable digital representations of the foot shape and have
      been successfully used in medical, ergonomic and footwear development
      applications. The increasing affordability of these systems presents
      opportunities for researchers investigating the foot and for manufacturers of
      foot related apparel and devices, particularly those interested in producing
      items that are customised to the individual. Suggestions are made for future
      areas of research and for the standardization of the protocols used to produce
      foot scans.

PMID- 20815915
TI  - Expression and clinical significance of multidrug resistance proteins in brain
      tumors.
AB  - BACKGROUND: To investigate the mechanisms of multidrug resistance of brain
      tumors, to identify the site of cellular expression of P-gp in human brains in
      situ and to morphologically determine whether an association may exist between P
      gp and caveolin-1. METHODS: Immunohistochemistry was used to detect the
      expression and location of P-glycoprotein (P-gp), multidrug resistance-associated
      protein (MDR), lung resistance-related protein (LRP), topoisomerase II (Topo II)
      and glutathione-S-pi (GST-pi) in 30 patient tumor tissues and 5 normal brain
      tissues. The sections were subjected to double labeling for P-gp (TRITC labeled)
      and caveolin-1 (FITC labeled). The location and characteristics of expression of
      the two proteins in the blood brain barrier(BBB) was observed using a laser
      scanning microscope. RESULTS: High expression of P-gp was detected in vessel
      walls and the tissue surrounding the vessels. However, expression of P-gp was low
      in tumor cells. The expression of the other 4 multidrug resistance proteins was
      not observed in the vessel walls. Laser scanning microscopy showed P-gp and
      caveolin-1 co-expression: the two proteins co-localized either in the luminal
      endothelial compartment or at the border of the luminal/abluminal compartments.
      CONCLUSION: Chemotherapeutics drugs are interrupted in the end-feet of
      neuroepithelial cells of the BBB by P-gp, which weakens the chemotherapeutic
      effect. P-gp marks the BBB, and the transporter is localized in the luminal
      endothelial compartment where it co-localizes with caveolin-1.

PMID- 20815916
TI  - Mtmr8 is essential for vasculature development in zebrafish embryos.
AB  - BACKGROUND: Embryonic morphogenesis of vascular and muscular systems is tightly
      coordinated, and a functional cooperation of Mtmr8 with PI3K in actin filament
      modeling and muscle development has been revealed in zebrafish. Here, we attempt
      to explore the function of Mtmr8 in vasculature development parallel to its
      function in muscle development. RESULTS: During early stage of somitogenesis,
      mtmr8 expression was detected in both somitic mesodem and ventral mesoderm.
      Knockdown of mtmr8 by morpholino impairs arterial endothelial marker expression,
      and results in endothelial cell reduction and vasculogenesis defects, such as
      retardation in intersegmental vessel development and interruption of trunk dorsal
      aorta. Moreover, mtmr8 morphants show loss of arterial endothelial cell identity
      in dorsal aorta, which is effectively rescued by low concentration of PI3K
      inhibitor, and by over-expression of dnPKA mRNA or vegf mRNA. Interestingly,
      mtmr8 expression is up-regulated when zebrafish embryos are treated with specific
      inhibitor of Hedgehog pathway that abolishes arterial marker expression.
      CONCLUSION: These data indicate that Mtmr8 is essential for vasculature
      development in zebrafish embryos, and may play a role in arterial specification
      through repressing PI3K activity. It is suggested that Mtmr8 should represent a
      novel element of the Hedgehog/PI3K/VEGF signaling cascade that controls arterial
      specification.

PMID- 20815917
TI  - The first Irish genome and ways of improving sequence accuracy.
AB  - Whole-genome sequencing of an Irish person reveals hundreds of thousands of novel
      genomic variants. Imputation using previous known information improves the
      accuracy of low-read-depth sequencing.

PMID- 20815919
TI  - A new tool for detection of type I interferon activation in systemic lupus
      erythematosus.
AB  - The IFN-I pathway is activated in systemic lupus erythematosus (SLE) and appears
      to be important in the pathogenesis of the disease. As a result, several clinical
      trials of anti-IFN monoclonal antibodies, which hold promise to control the
      disease, have been launched. Additionally, activation of IFN-I might be important
      in the prognosis and activity assessment of the disease. Therefore, new
      biomarkers that reflect activity of the IFN-I pathway and are simple to measure,
      such as the monocyte CD64 receptor, are expected to have a great impact on the
      management of SLE, if properly validated.

PMID- 20815918
TI  - New developments in osteoarthritis. Prevention of injury-related knee
      osteoarthritis: opportunities for the primary and secondary prevention of knee
      osteoarthritis.
AB  - Where risk factors have been identified in knee and hip osteoarthritis (OA), with
      few exceptions, no prevention strategies have proven beneficial. The major risk
      factors for knee OA are advanced age, injury and obesity. However, there is
      limited or no evidence that they are modifiable or to what degree modifying them
      is effective in preventing development of knee OA or in preventing symptoms and
      progressive disease in persons with early OA. The notable exception is the
      growing epidemic of (sports) injury related knee OA. This review details the
      biological and clinical data indicating the efficacy of interventions targeting
      neuromuscular and biomechanical factors that make this subset of OA an attractive
      public health target, and highlights research opportunities for the future.

PMID- 20815920
TI  - Epigenetics of renal cell carcinoma: the path towards new diagnostics and
      therapeutics.
AB  - Aberrant DNA methylation, in particular promoter hypermethylation and
      transcriptional silencing of tumor suppressor genes, has an important role in the
      development of many human cancers, including renal cell carcinoma (RCC). Indeed,
      apart from mutations in the well studied von Hippel-Lindau gene (VHL), the
      mutation frequency rates of known tumor suppressor genes in RCC are generally
      low, but the number of genes found to show frequent inactivation by promoter
      methylation in RCC continues to grow. Here, we review the genes identified as
      epigenetically silenced in RCC and their relationship to pathways of tumor
      development. Increased understanding of RCC epigenetics provides new insights
      into the molecular pathogenesis of RCC and opportunities for developing novel
      strategies for the diagnosis, prognosis and management of RCC.

PMID- 20815921
TI  - An exploratory study of Muslim adolescents' views on sexuality: Implications for
      sex education and prevention.
AB  - BACKGROUND: This paper describes the results of an exploratory qualitative study
      on Muslim adolescents' views on sexuality in the Netherlands. METHODS: Data were
      gathered from an Internet forum on which 44 Muslim and 33 non-Muslim adolescents
      discussed sexuality as it relates to Islam. These discussions were subsequently
      analyzed for content using Nvivo 2.0. RESULTS: Our analysis revealed several
      issues that are relevant for the design of future sex education programs
      targeting Muslim youth. Apart from some expected outcomes regarding, for example,
      taboos on sexuality, sex outside marriage, abortion, homosexuality and
      conservative gender roles, our analyses showed that in cases of disputes 1)
      discussions were polarized, 2) opponents used the same Qur'anic passages to
      support their views, and 3) the authority of an Imam was questioned when his
      interpretation of Qur'anic passages was not in line with the views of
      participants. CONCLUSIONS: Our findings show that current approaches to sex
      education among Muslim youth are likely to be unsuccessful given the rigidity of
      sexual norms in Muslim society. In addition, we also identified new barriers to
      sex education among Muslim youth (e.g. lack of respect for an Imam who opposes a
      youth's views on sexuality).

PMID- 20815922
TI  - Expression of tryptophan 2,3-dioxygenase in mature granule cells of the adult
      mouse dentate gyrus.
AB  - New granule cells are continuously generated in the dentate gyrus of the adult
      hippocampus. During granule cell maturation, the mechanisms that differentiate
      new cells not only describe the degree of cell differentiation, but also
      crucially regulate the progression of cell differentiation. Here, we describe a
      gene, tryptophan 2,3-dioxygenase (TDO), whose expression distinguishes stem cells
      from more differentiated cells among the granule cells of the adult mouse dentate
      gyrus. The use of markers for proliferation, neural progenitors, and immature and
      mature granule cells indicated that TDO was expressed in mature cells and in some
      immature cells. In mice heterozygous for the alpha-isoform of calcium/calmodulin
      dependent protein kinase II, in which dentate gyrus granule cells fail to mature
      normally, TDO immunoreactivity was substantially downregulated in the dentate
      gyrus granule cells. Moreover, a 5-bromo-2'-deoxyuridine labeling experiment
      revealed that new neurons began to express TDO between 2 and 4 wk after the
      neurons were generated, when the axons and dendrites of the granule cells
      developed and synaptogenesis occurred. These findings indicate that TDO might be
      required at a late-stage of granule cell development, such as during axonal and
      dendritic growth, synaptogenesis and its maturation.

PMID- 20815923
TI  - Towards the simplification of MHC typing protocols: targeting classical MHC class
      II genes in a passerine, the pied flycatcher Ficedula hypoleuca.
AB  - BACKGROUND: Major Histocompatibility Complex (MHC) has drawn the attention of
      evolutionary biologists due to its importance in crucial biological processes,
      such as sexual selection and immune response in jawed vertebrates. However, the
      characterization of classical MHC genes subjected to the effects of natural
      selection still remains elusive in many vertebrate groups. Here, we have tested
      the suitability of flanking intron sequences to guide the selective exploration
      of classical MHC genes driving the co-evolutionary dynamics between pathogens and
      their passerine (Aves, Order Passeriformes) hosts. FINDINGS: Intronic sequences
      flanking the usually polymorphic exon 2 were isolated from different species
      using primers sitting on conserved coding regions of MHC class II genes (beta
      chain). Taking the pied flycatcher Ficedula hypoleuca as an example, we
      demonstrate that careful primer design can evade non-classical MHC gene and
      pseudogene amplification. At least four polymorphic and expressed loci were co
      replicated using a single pair of primers in five non-related individuals (N = 28
      alleles). The cross-amplification and preliminary inspection of similar MHC
      fragments in eight unrelated songbird taxa suggests that similar approaches can
      also be applied to other species. CONCLUSIONS: Intron sequences flanking the
      usually polymorphic exon 2 may assist the specific investigation of classical MHC
      class II B genes in species characterized by extensive gene duplication and
      pseudogenization. Importantly, the evasion of non-classical MHC genes with a more
      specific function and non-functional pseudogenes may accelerate data collection
      and diminish lab costs. Comprehensive knowledge of gene structure, polymorphism
      and expression profiles may be useful not only for the selective examination of
      evolutionarily relevant genes but also to restrict chimera formation by
      minimizing the number of co-amplifying loci.

PMID- 20815924
TI  - Conflicting results of prenatal FISH with different probes for Down's Syndrome
      critical regions associated with mosaicism for a de novo del(21)(q22)
      characterised by molecular karyotyping: Case report.
AB  - For the rapid detection of common aneuploidies either PCR or Fluorescence in
      situ hybridisation (FISH) on uncultured amniotic fluid cells are widely used.
      There are different commercial suppliers providing FISH assays for the detection
      of trisomies affecting the Down's syndrome critical regions (DSCR) in 21q22. We
      present a case in which rapid FISH screening with different commercial probes for
      the DSCR yielded conflicting results. Chromosome analysis revealed a deletion of
      one chromosome 21 in q22 which explained the findings. Prenatally an additional
      small supernumerary marker chromosome (sSMC) was discovered as well, which could
      not be characterised. Postnatal chromosome analysis in lymphocytes of the infant
      revealed complex mosaicism with four cell lines. By arrayCGH the sSMC was
      provisionally described as derivative chromosome 21 which was confirmed by
      targeted FISH experiments.

PMID- 20815925
TI  - Harvest: an open-source tool for the validation and improvement of peptide
      identification metrics and fragmentation exploration.
AB  - BACKGROUND: Protein identification using mass spectrometry is an important tool
      in many areas of the life sciences, and in proteomics research in particular.
      Increasing the number of proteins correctly identified is dependent on the
      ability to include new knowledge about the mass spectrometry fragmentation
      process, into computational algorithms designed to separate true matches of
      peptides to unidentified mass spectra from spurious matches. This discrimination
      is achieved by computing a function of the various features of the potential
      match between the observed and theoretical spectra to give a numerical
      approximation of their similarity. It is these underlying "metrics" that
      determine the ability of a protein identification package to maximise correct
      identifications while limiting false discovery rates. There is currently no
      software available specifically for the simple implementation and analysis of
      arbitrary novel metrics for peptide matching and for the exploration of
      fragmentation patterns for a given dataset. RESULTS: We present Harvest: an open
      source software tool for analysing fragmentation patterns and assessing the power
      of a new piece of information about the MS/MS fragmentation process to more
      clearly differentiate between correct and random peptide assignments. We
      demonstrate this functionality using data metrics derived from the properties of
      individual datasets in a peptide identification context. Using Harvest, we
      demonstrate how the development of such metrics may improve correct peptide
      assignment confidence in the context of a high-throughput proteomics experiment
      and characterise properties of peptide fragmentation. CONCLUSIONS: Harvest
      provides a simple framework in C++ for analysing and prototyping metrics for
      peptide matching, the core of the protein identification problem. It is not a
      protein identification package and answers a different research question to
      packages such as Sequest, Mascot, X!Tandem, and other protein identification
      packages. It does not aim to maximise the number of assigned peptides from a set
      of unknown spectra, but instead provides a method by which researchers can
      explore fragmentation properties and assess the power of novel metrics for
      peptide matching in the context of a given experiment. Metrics developed using
      Harvest may then become candidates for later integration into protein
      identification packages.

PMID- 20815927
TI  - Sequencing bias: comparison of different protocols of microRNA library
      construction.
AB  - BACKGROUND: MicroRNAs(miRNAs) are 18-25 nt small RNAs playing critical roles in
      many biological processes. The majority of known miRNAs were discovered by
      conventional cloning and a Sanger sequencing approach. The next-generation
      sequencing (NGS) technologies enable in-depth characterization of the global
      repertoire of miRNAs, and different protocols for miRNA library construction have
      been developed. However, the possible bias between the relative expression levels
      and sequences introduced by different protocols of library preparation have
      rarely been explored. RESULTS: We assessed three different miRNA library
      preparation protocols, SOLiD, Illumina versions 1 and 1.5, using cloning or SBS
      sequencing of total RNA samples extracted from skeletal muscles from Hu sheep and
      Dorper sheep, and then validated 9 miRNAs by qRT-PCR. Our results show that SBS
      sequencing data highly correlate with Illumina cloning data. The SOLiD data, when
      compared to Illumina's, indicate more dispersed distribution of length, higher
      frequency variation for nucleotides near the 3'- and 5'-ends, higher frequency
      occurrence for reads containing end secondary structure (ESS), and higher
      frequency for reads that do not map to known miRNAs. qRT-PCR results showed the
      best correlation with SOLiD cloning data. Fold difference of Hu sheep and Dorper
      sheep between qRT-PCR result and SBS sequencing data correlated well (r = 0.937),
      and fold difference of miR-1 and miR-206 among SOLiD cloning data, qRT-PCR and
      SBS sequencing data was similar. CONCLUSIONS: The sequencing depth can influence
      the quantitative measurement of miRNA abundance, but the discrepancy caused by it
      was not statistically significant as high correlation was observed between
      Illumina cloning and SBS sequencing data. Bias of length distribution, sequence
      variation, and ESS was observed between data obtained with the different
      protocols. SOLiD cloning data differ from Illumina cloning data mainly because of
      distinct methods of adapter ligation. The good correlation between qRT-PCR result
      and SOLiD data might be due to the similarities of the hybridization-based
      methods. The fold difference analysis indicated that methods based on
      hybridization may be superior for quantitative measurement of miRNA abundance.
      Because of the genome sequence of the sheep is not available, our data may not
      explain how the entire miRNA bias in the natural miRNAs in sheep or other mammal
      miRNA expression, unbiased artificially synthesized miRNA will help on evaluating
      the methodology of miRNA library preparation.

PMID- 20815926
TI  - Beneficial effect of agmatine on brain apoptosis, astrogliosis, and edema after
      rat transient cerebral ischemia.
AB  - BACKGROUND: Although agmatine therapy in a mouse model of transient focal
      cerebral ischemia is highly protective against neurological injury, the
      mechanisms underlying the protective effects of agmatine are not fully
      elucidated. This study aimed to investigate the effects of agmatine on brain
      apoptosis, astrogliosis and edema in the rats with transient cerebral ischemia.
      METHODS: Following surgical induction of middle cerebral artery occlusion (MCAO)
      for 90 min, agmatine (100 mg/kg, i.p.) was injected 5 min after beginning of
      reperfusion and again once daily for the next 3 post-operative days. Four days
      after reperfusion, both motor and proprioception functions were assessed and then
      all rats were sacrificed for determination of brain infarct volume (2, 3, 5
      triphenyltetrazolium chloride staining), apoptosis (TUNEL staining), edema (both
      cerebral water content and amounts of aquaporin-4 positive cells), gliosis (glial
      fibrillary acidic protein [GFAP]-positive cells), and neurotoxicity (inducible
      nitric oxide synthase [iNOS] expression). RESULTS: The results showed that
      agmatine treatment was found to accelerate recovery of motor (from 55 degrees to
      62 degrees) and proprioception (from 54% maximal possible effect to 10% maximal
      possible effect) deficits and to prevent brain infarction (from 370 mm3 to 50
      mm3), gliosis (from 80 GFAP-positive cells to 30 GFAP-positive cells), edema
      (cerebral water contents decreased from 82.5% to 79.4%; AQP4 positive cells
      decreased from 140 to 84 per section), apoptosis (neuronal apoptotic cells
      decreased from 100 to 20 per section), and neurotoxicity (iNOS expression cells
      decreased from 64 to 7 per section) during MCAO ischemic injury in rats.
      CONCLUSIONS: The data suggest that agmatine may improve outcomes of transient
      cerebral ischemia in rats by reducing brain apoptosis, astrogliosis and edema.

PMID- 20815928
TI  - Dynamics of HEV viremia, fecal shedding and its relationship with transaminases
      and antibody response in patients with sporadic acute hepatitis E.
AB  - BACKGROUND: There is paucity of data regarding duration of fecal excretion and
      viremia on sequential samples from individual patients and its correlation with
      serum transaminases and antibody responses in patients with acute hepatitis E.
      This prospective study was undertaken at a tertiary care center in Northern India
      over 15 months. Only those patients of sporadic acute hepatitis E who were in
      their first week of illness and followed up weekly for liver function tests, IgM
      anti HEV antibody and HEV RNA in sera and stool were included. HEV RNA was done
      by RT - nPCR using two pairs of primers from RdRp region of ORF 1 of the HEV
      genome. RESULTS: Over a period of 15 months 60 patients met the inclusion
      criterion and were enrolled for the final analysis. The mean age of the patients
      was 29.2 +/- 8.92 years, there were 39 males. The positivity of IgM anti HEV was
      80% at diagnosis and 18.3% at 7th week, HEV RNA 85% at diagnosis and 6.6% at 7th
      week and fecal RNA 70% at the time of diagnosis and 20% at 4th week. The maximum
      duration of viremia detected was 42 days and fecal viral shedding was 28 days
      after the onset of illness. CONCLUSION: Present study reported HEV RNA positivity
      in sera after normalization of transaminases. Fecal shedding was not seen beyond
      normalization of transaminases. However, viremia lasted beyond normalization of
      transaminases suggesting that liver injury is independent of viral replication.

PMID- 20815929
TI  - Combining ketamine with astrocytic inhibitor as a potential analgesic strategy
      for neuropathic pain ketamine, astrocytic inhibitor and pain.
AB  - BACKGROUND: Neuropathic pain is an intractable clinical problem. Intrathecal
      ketamine, a noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist, is
      reported to be useful for treating neuropathic pain in clinic by inhibiting the
      activity of spinal neurons. Nevertheless, emerging studies have disclosed that
      spinal astrocytes played a critical role in the initiation and maintenance of
      neuropathic pain. However, the present clinical therapeutics is still just
      concerning about neuronal participation. Therefore, the present study is to
      validate the coadministration effects of a neuronal noncompetitive N-methyl-D
      aspartate receptor (NMDAR) antagonist ketamine and astrocytic cytotoxin L-alpha
      aminoadipate (LAA) on spinal nerve ligation (SNL)-induced neuropathic pain.
      RESULTS: Intrathecal ketamine (10, 100, 1000 MUg/kg) or LAA (10, 50, 100 nmol)
      alleviated SNL-induced mechanical allodynia in a dose-dependent manner
      respectively. Phosphorylated NR1 (pNR1) or glial fibrillary acidic protein (GFAP)
      expression was down-regulated by intrathecal ketamine (100, 1000 MUg/kg) or LAA
      (50, 100 nmol) respectively. The combination of ketamine (100 MUg/kg) with LAA
      (50 nmol) showed superadditive effects on neuropathic pain compared with that of
      intrathecal administration of either ketamine or LAA alone. Combined
      administration obviously relieved mechanical allodynia in a quick and stable
      manner. Moreover, down-regulation of pNR1 and GFAP expression were also enhanced
      by drugs coadministration. CONCLUSIONS: These results suggest that combining
      NMDAR antagonist ketamine with an astrocytic inhibitor or cytotoxin, which is
      suitable for clinical use once synthesized, might be a potential strategy for
      clinical management of neuropathic pain.

PMID- 20815930
TI  - Adequacy and quality of abdominal echographies requested by primary care
      professionals.
AB  - BACKGROUND: The value of abdominal echography in primary care is great because it
      is innocuous, inexpensive, easy to perform and provides a great deal of
      information making this the first examination to be requested in cases of
      probable abdominal disease. However, too many abdominal echographies are probably
      requested overcrowding the Departments of Radiodiagnosis with not always
      justified petitions or with repetition of tests based on little clinical
      criteria. METHODS/DESIGN: The aim of the study is to evaluate the adequacy and
      quality of abdominal echographies requested by primary care physicians in the
      Maresme County (North of Barcelona), develop guidelines for indicating
      echographies and reevaluate this adequacy after implementing these guidelines.We
      will perform a two-phase study: the first descriptive, and retrospective
      evaluating the adequacy and quality of petitions for abdominal echographies, and
      in the second phase we will evaluate the impact of recommendations for indicating
      abdominal echographies for PC physicians on the adequacy and quality of
      echography petitions thereafter.This study will be carried out in 10 primary care
      centres in the Maresme (Barcelona).1067 abdominal echographies requested by
      primary care physicians from the above mentioned centres from January 2007 to
      April 2010 and referred to the Department of Radiology and the same number of
      applications after the intervention.All the petitions for abdominal echographies
      requested will be analysed and the clinical histories will be obtained to
      determine demographic variables, the reason for the visit and for the echography
      petition and diagnostic orientation, clinical and echographic data, evaluation of
      the echographies according to the quality and variables characterising the
      professionals requesting the echographies including: age, sex, laboral situation,
      length of time in work post, formation, etc.To achieve a consensus of the
      adequacy of abdominal echography, a work group including gastroenterologists,
      radiologists and general practitioners will be created following the nominal
      group. This will allow the design of guidelines for the indication of abdominal
      echography and posterior evaluation of their impact among physicians by diffusion
      and posterior reevaluation of the adequacy of the petitions.

PMID- 20815931
TI  - Self-reported sexually transmitted infections and their correlates among men who
      have sex with men in Norway: an Internet-based cross-sectional survey.
AB  - BACKGROUND: The incidences of reportable sexually transmitted infections (STI)
      among men who have sex with men (MSM) have increased since the late 1990 s in
      Norway. The objectives of our study were to assess factors, associated with
      recent selected STI among MSM, living in Norway in order to guide prevention
      measures. METHODS: We conducted a cross-sectional Internet-based survey during 1
      19 October 2007 among members of a MSM-oriented Norwegian website using an
      anonymous questionnaire on demographics, sexual behaviour, drug and alcohol use,
      and STI. The studied outcomes were gonorrhoea, syphilis, HIV or Chlamydia
      infection in the previous 12 months. Associations between self-reported selected
      STI and their correlates were analysed by multivariable Poisson regression. P
      value for trend (p-trend), adjusted prevalence ratios (PR) with 95% confidence
      intervals [] were calculated. RESULTS: Among 2430 eligible 16-74 years old
      respondents, 184 (8%) reported having had one of the following: syphilis (n =
      17), gonorrhoea (n = 35), HIV (n = 42) or Chlamydia (n = 126) diagnosed in the
      past 12 months. Reporting Chlamydia was associated with non-western background
      (PR 2.8 [1.4-5.7]), number of lifetime male partners (p-trend < 0.001), unsafe
      sex under the influence of alcohol (PR 1.8 [1.1-2.9]) and with younger age (p
      trend = 0.002). Reporting gonorrhoea was associated with unrevealed background
      (PR 5.9 [1.3-26.3]), having more than 50 lifetime male partners (PR 4.5 [1.3
      15.6]) and more than 5 partners in the past 6 months (PR 3.1 [1.1-8.8]), while
      mid-range income was protective (PR 0.1 [0.0-0.6]). Reporting HIV was associated
      with residing in Oslo or Akershus county (PR 2.3 [1.2-4.6]), non-western
      background (PR 5.4 [1.9-15.3]), unrevealed income (PR 10.4 [1.5-71.4]), number of
      lifetime male partners (p-trend < 0.001) and being under the influence of
      selected drugs during sex in the past 12 months (PR 5.2 [2.7-11.4]). In addition,
      the frequency of feeling drunk was reversibly associated with HIV. CONCLUSIONS:
      Our study demonstrates different associations of demographic and behavioural
      factors with different STI outcomes in the study population. Number of lifetime
      male partners was the most important potential predictor for Chlamydia and HIV.
      The STI prevention efforts among MSM should focus on Oslo and Akershus, promote
      safe sex practices and tackle sex-related drug and alcohol use.

PMID- 20815932
TI  - Infant feeding counselling in Uganda in a changing environment with focus on the
      general population and HIV-positive mothers - a mixed method approach.
AB  - BACKGROUND: Health workers' counselling practices are essential to improve infant
      feeding practices. This paper will assess how infant feeding counselling was done
      and experienced by counsellors and mothers in Eastern Uganda in the context of
      previous guidelines. This has implications for implementation of the new infant
      feeding guidelines from 2009. METHODS: This paper combines qualitative and
      quantitative data from Mbale District in Eastern Uganda. Data was collected from
      2003 to 2005 in a mixed methods approach. This includes: key-informant interviews
      among eighteen health workers in the public hospital, health clinics and non
      governmental organisations working with people living with HIV, fifteen focus
      group discussions in the general population and among clients from an HIV clinic,
      two cross-sectional surveys including 727 mothers from the general population and
      235 HIV-positive mothers. RESULTS: The counselling sessions were often
      improvised. Health workers frequently had pragmatic approaches to infant feeding
      as many clients struggled with poverty, stigma and non-disclosure of HIV. The
      feasibility of the infant feeding recommendations was perceived as challenging
      among health workers, both for HIV-positive mothers and in the general
      population. Group counselling with large groups was common in the public health
      service. Some extra infant feeding teaching capacities were mobilised for care
      takers of undernourished children. A tendency to simplify messages giving one
      sided information was seen. Different health workers presented contradicting
      simplified perspectives in some cases. Outdated training was a common concern
      with many health workers not being given courses or seminars on infant feeding
      since professional graduation. Other problems were minimal staffing, lack of
      resources, and programs being started and subsequently stopped abruptly. Many of
      the HIV-counsellors in the non-governmental organisations got extended training
      in counselling which seemed to be beneficial. CONCLUSIONS: Health workers were
      faced with challenges related to workload, resources, scientific updating, and
      also a need to adjust to frequent changes in programs, recommendations and
      guidelines. The clients were faced with difficult choices, poverty, lack of
      education and stigma. Feasibility of the recommendations was a major concern.
      Systematic approaches to update health workers should be a priority.

PMID- 20815933
TI  - A brief intervention is sufficient for many adolescents seeking help from low
      threshold adolescent psychiatric services.
AB  - BACKGROUND: There has been a considerable increase in the need for psychiatric
      services for adolescents. Primary health care practitioners have a major role in
      detecting, screening and helping these adolescents. An intervention entitled
      SCREEN is described in this article. The SCREEN intervention was developed to
      help practitioners to detect and screen adolescent needs, to care for adolescents
      at the primary health care level and to facilitate the referral of adolescents to
      secondary care services in collaboration between primary and secondary health
      care. Secondly, the article presents the background and clinical characteristics
      of youths seeking help from the SCREEN services, and compares the background
      factors and clinical characteristics of those patients referred and not referred
      to secondary care services. METHODS: The SCREEN intervention consisted of 1 to 5
      sessions, including assessment by a semi-structured anamnesis interview, the
      structured Global Assessment Scale, and by a structured priority rating scale, as
      well as a brief intervention for each adolescent's chosen problem. Parents took
      part in the assessment in 39% of cases involving girls and 50% involving boys.
      During 34 months, 2071 adolescents (69% females) entered the intervention and 70%
      completed it. The mean age was 17.1 years for boys and 17.3 years for girls.
      RESULTS: For 69% of adolescents, this was the first contact with psychiatric
      services. The most common reasons for seeking services were depressive symptoms
      (31%). Self-harming behaviour had occurred in 25% of girls and 16% of boys. The
      intervention was sufficient for 37% of those who completed it. Psychosocial
      functioning improved during the intervention. Factors associated with referral
      for further treatment were female gender, anxiety as the main complaint, previous
      psychiatric treatment, self-harming behaviour, a previous need for child welfare
      services, poor psychosocial functioning and a high score in the priority rating
      scale. CONCLUSIONS: A brief intervention carried out by a team including
      professionals from both primary and secondary level services was sufficient for a
      considerable proportion of adolescents seeking help for their psychiatric
      problems. Referral practices and counselling in special level services can be
      standardized. In the future, it will be important to develop and assess
      psychiatric services for adolescents using randomised controlled trials.

PMID- 20815934
TI  - Partial motor status epilepticus as a clinical manifestation of carotid stenosis.
AB  - Limb shaking (LS) is often confused with focal motor seizures. Distinguishing
      between both is crucial, because LS may represent an indicator of severe carotid
      occlusive disease and patients are at high risk of stroke. We report the case of
      a patient with occlusive carotid stenosis without definite stroke who develops
      partial motor status epilepticus (SE). Clinical, neuroimaging and
      electroencephalographic findings are provided. We conclude that focal motor
      seizures should be distinguished from LS based on clinical and
      electroencephalographic findings.

PMID- 20815935
TI  - Evidence of D-phenylglycine as delivering tool for improving L-dopa absorption.
AB  - BACKGROUND: L-dopa has been used for Parkinson's disease management for a long
      time. However, its wide variety in the rate and the extent of absorption remained
      challenge in designing suitable therapeutic regime. We report here a design of
      using D-phenylglycine to guard L-dopa for better absorption in the intestine via
      intestinal peptide transporter I (PepT1). METHODS: D-phenylglycine was chemically
      attached on L-dopa to form D-phenylglycine-L-dopa as a dipeptide prodrug of L
      dopa. The cross-membrane transport of this dipeptide and L-dopa via PepT1 was
      compared in brush-boarder membrane vesicle (BBMV) prepared from rat intestine.
      The intestinal absorption was compared by in situ jejunal perfusion in rats. The
      pharmacokinetics after i.v. and p.o. administration of both compounds were also
      compared in Wistar rats. The striatal dopamine released after i.v. administration
      of D-phenylglycine-L-dopa was collected by brain microdialysis and monitored by
      HPLC. Anti-Parkinsonism effect was determined by counting the rotation of 6-OHDA
      treated unilateral striatal lesioned rats elicited rotation with (+)
      methamphetamine (MA). RESULTS: The BBMV uptake of D-phenylglycine-L-dopa was
      inhibited by Gly-Pro, Gly-Phe and cephradine, the typical PepT1 substrates, but
      not by amino acids Phe or L-dopa. The cross-membrane permeability (Pm*)
      determined in rat jejunal perfusion of D-phenylglycine-L-dopa was higher than
      that of L-dopa (2.58 +/- 0.14 vs. 0.94 +/- 0.10). The oral bioavailability of D
      phenylglycine-L-dopa was 31.7 times higher than that of L-dopa in rats. A
      sustained releasing profile of striatal dopamine was demonstrated after i. v.
      injection of D-phenylglycine-L-dopa (50 mg/kg), indicated that D-phenylglycine-L
      dopa might be a prodrug of dopamine. D-phenylglycine-L-dopa was more efficient
      than L-dopa in lowering the rotation of unilateral striatal lesioned rats (19.1
      +/- 1.7% vs. 9.9 +/- 1.4%). CONCLUSION: The BBMV uptake studies indicated that D
      phenylglycine facilitated the transport of L-dopa through the intestinal PepT1
      transporter. The higher jejunal permeability and the improved systemic
      bioavailability of D-phenylglycine-L-dopa in comparison to that of l-dopa
      suggested that D-phenylglycine is an effective delivery tool for improving the
      oral absorption of drugs like L-dopa with unsatisfactory pharmacokinetics. The
      gradual release of dopamine in brain striatum rendered this dipeptide as a
      potential dopamine sustained-releasing prodrug.

PMID- 20815936
TI  - Functional characterization of the protein C A267T mutation: evidence for
      impaired secretion due to defective intracellular transport.
AB  - BACKGROUND: Activated protein C (PC) is a serine protease that regulates blood
      coagulation by inactivating coagulation factors Va and VIIIa. PC deficiency is an
      autosomally inherited disorder associated with a high risk of recurrent venous
      thrombosis. The aim of the study was to explore the mechanisms responsible for
      severe PC deficiency in a patient with the protein C A267T mutation by in-vitro
      expression studies. RESULTS: Huh7 and CHO-K1 cells were transiently transfected
      with expression vectors containing wild-type (WT PC) and mutated PC (A267T PC)
      cDNAs. PC mRNA levels were assessed by qRT-PCR and the PC protein levels were
      measured by ELISA. The mRNA levels of WT PC and A267T PC were similar, while the
      intracellular protein level of A267T PC was moderately decreased compared to WT
      PC. The secretion of A267T PC into the medium was severely impaired. No
      differences in molecular weights were observed between WT and A267T PC before and
      after treatment with endo-beta-N-acetylglucosaminidase. Proteasomal and lysosomal
      degradations were examined using lactacystin and bafilomycin, respectively, and
      revealed that A267T PC was slightly more susceptible for proteasomal degradation
      than WT PC. Intracellular co-localization analysis indicated that A267T PC was
      mainly located in the endoplasmic reticulum (ER), whereas WT PC was observed in
      both ER and Golgi. CONCLUSIONS: In contrast to what has been reported for other
      PC mutants, intracellular degradation of A267T PC was not the main/dominant
      mechanism underlying the reduced intracellular and secretion levels of PC. Our
      results indicate that the A267T mutation most likely caused misfolding of PC,
      which might lead to increased retention of the mutated PC in ER.

PMID- 20815937
TI  - Depression as a predictor of work resumption following myocardial infarction
      (MI): a review of recent research evidence.
AB  - BACKGROUND: Depression often coexists with myocardial infarction (MI) and has
      been found to impede recovery through reduced functioning in key areas of life
      such as work. In an era of improved survival rates and extended working lives, we
      review whether depression remains a predictor of poorer work outcomes following
      MI by systematically reviewing literature from the past 15 years. METHODS:
      Articles were identified using medical, health, occupational and social science
      databases, including PubMed, OVID, Medline, Proquest, CINAHL plus, CCOHS, SCOPUS,
      Web of Knowledge, and the following pre-determined criteria were applied: (i)
      collection of depression measures (as distinct from 'psychological distress') and
      work status at baseline, (ii) examination and statistical analysis of predictors
      of work outcomes, (iii) inclusion of cohorts with patients exhibiting symptoms
      consistent with Acute Coronary Syndrome (ACS), (iv) follow-up of work-specific
      and depression specific outcomes at minimum 6 months, (v) published in English
      over the past 15 years. Results from included articles were then evaluated for
      quality and analysed by comparing effect size. RESULTS: Of the 12 articles
      meeting criteria, depression significantly predicted reduced likelihood of return
      to work (RTW) in the majority of studies (n = 7). Further, there was a trend
      suggesting that increased depression severity was associated with poorer RTW
      outcomes 6 to 12 months after a cardiac event. Other common significant
      predictors of RTW were age and patient perceptions of their illness and work
      performance. CONCLUSION: Depression is a predictor of work resumption post-MI. As
      work is a major component of Quality of Life (QOL), this finding has clinical,
      social, public health and economic implications in the modern era. Targeted
      depression interventions could facilitate RTW post-MI.

PMID- 20815938
TI  - Overview of research activities associated with the World Health Organization:
      results of a survey covering 2006/07.
AB  - BACKGROUND: This paper presents the first comprehensive effort to provide an
      overview of the research associated with the World Health Organization (WHO)
      headquarters in 2006/07. METHODS: Information was obtained by questionnaire and
      interviews with senior staff operating at WHO headquarters in Geneva. Research
      type, purpose and resources (both financial and staff) were defined and compared
      for each of the 37 departments identified and a comparative analysis was made
      with the global burden of disease as expressed by Disability Adjusted Life Years
      (DALY). RESULTS: Research expenditure in 2006/07 was estimated at US$215 million.
      WHO is involved in more than 60 research networks/partnerships and often WHO
      itself is the network host.Using the DALY model, 84% of the funding WHO allocates
      to research goes to DALY Type I diseases (communicable, maternal, perinatal and
      nutritional diseases) which represents 40% of DALY. 4% is allocated to Daly Type
      II (non-communicable diseases) which contributes to 48% of DALY.45% of WHO
      permanent staff are involved with health research and the WHO's approach to
      research is predominantly focused on policy, advocacy, health systems and
      population based research. The Organization principally undertakes secondary
      research using published data and commissions others to conduct this work through
      contracts or research grants. This approach is broadly in line with the stated
      strategy of the Organization. CONCLUSIONS: The difficulty in undertaking this
      survey highlights the complexity of obtaining an Organization-wide assessment of
      research activity in the absence of common standards for research classification,
      methods for priority setting and a mechanism across WHO, or within the governance
      of global health research more generally, for managing a research portfolio.This
      paper presents a strategic birds-eye view of the WHO research portfolio using
      methodologies that, with further development, may provide the strategic
      information required if there is to be balancing of research efforts between
      communicable disease, non-communicable disease and other pressing public health
      needs. As the rollout of the WHO strategy on research for health proceeds we
      would hope to see similar exercises undertaken at the WHO Regional Offices and in
      support of capacity building of national health research systems within Member
      States.

PMID- 20815940
TI  - Constraints to estimating the prevalence of trypanosome infections in East
      African zebu cattle.
AB  - BACKGROUND: In East Africa, animal trypanosomiasis is caused by many tsetse
      transmitted protozoan parasites including Trypanosoma vivax, T. congolense and
      subspecies of T. brucei s.l. (T. b. brucei and zoonotic human infective T. b.
      rhodesiense) that may co-circulate in domestic and wild animals. Accurate species
      specific prevalence measurements of these parasites in animal populations are
      complicated by mixed infections of trypanosomes within individual hosts, low
      parasite densities and difficulties in conducting field studies. Many Polymerase
      Chain Reaction (PCR) based diagnostic tools are available to characterise and
      quantify infection in animals. These are important for assessing the contribution
      of infections in animal reservoirs and the risk posed to humans from zoonotic
      trypanosome species. New matrices for DNA capture have simplified large scale
      field PCR analyses but few studies have examined the impact of these techniques
      on prevalence estimations. RESULTS: The Whatman FTA matrix has been evaluated
      using a random sample of 35 village zebu cattle from a population naturally
      exposed to trypanosome infection. Using a generic trypanosome-specific PCR,
      prevalence was systematically evaluated. Multiple PCR samples taken from single
      FTA cards demonstrated that a single punch from an FTA card is not sufficient to
      confirm the infectivity status of an individual animal as parasite DNA is
      unevenly distributed across the card. At low parasite densities in the host, this
      stochastic sampling effect results in underestimation of prevalence based on
      single punch PCR testing. Repeated testing increased the estimated prevalence of
      all Trypanosoma spp. from 9.7% to 86%. Using repeat testing, a very high
      prevalence of pathogenic trypanosomes was detected in these local village cattle:
      T. brucei (34.3%), T. congolense (42.9%) and T. vivax (22.9%). CONCLUSIONS: These
      results show that, despite the convenience of Whatman FTA cards and specific PCR
      based detection tools, the chronically low parasitaemias in indigenous African
      zebu cattle make it difficult to establish true prevalence. Although this study
      specifically applies to FTA cards, a similar effect would be experienced with
      other approaches using blood samples containing low parasite densities. For
      example, using blood film microscopy or PCR detection from liquid samples where
      the probability of detecting a parasite or DNA molecule, in the required number
      of fields of view or PCR reaction, is less than one.

PMID- 20815941
TI  - Chromosome spreading of associated transposable elements and ribosomal DNA in the
      fish Erythrinus erythrinus. Implications for genome change and karyoevolution in
      fish.
AB  - BACKGROUND: The fish, Erythrinus erythrinus, shows an interpopulation diversity,
      with four karyomorphs differing by chromosomal number, chromosomal morphology and
      heteromorphic sex chromosomes. Karyomorph A has a diploid number of 2n = 54 and
      does not have differentiated sex chromosomes. Karyomorph D has 2n = 52
      chromosomes in females and 2n = 51 in males, and it is most likely derived from
      karyomorph A by the differentiation of a multiple X1X2Y sex chromosome system. In
      this study, we analyzed karyomorphs A and D by means of cytogenetic approaches to
      evaluate their evolutionary relationship. RESULTS: Conspicuous differences in the
      distribution of the 5S rDNA and Rex3 non-LTR retrotransposon were found between
      the two karyomorphs, while no changes in the heterochromatin and 18S rDNA
      patterns were found between them. Rex3 was interstitially dispersed in most
      chromosomes. It had a compartmentalized distribution in the centromeric regions
      of only two acrocentric chromosomes in karyomorph A. In comparison, in karyomorph
      D, Rex3 was found in 22 acrocentric chromosomes in females and 21 in males. All
      5S rDNA sites co-localized with Rex3, suggesting that these are associated in the
      genome. In addition, the origin of the large metacentric Y chromosome in
      karyomorph D by centric fusion was highlighted by the presence of internal
      telomeric sites and 5S rDNA/Rex3 sites on this chromosome. CONCLUSION: We
      demonstrated that some repetitive DNAs (5S rDNA, Rex3 retroelement and (TTAGGG)n
      telomeric repeats) were crucial for the evolutionary divergence inside E.
      erythrinus. These elements were strongly associated with the karyomorphic
      evolution of this species. Our results indicate that chromosomal rearrangements
      and genomic modifications were significant events during the course of evolution
      of this fish. We detected centric fusions that were associated with the
      differentiation of the multiple sex chromosomes in karyomorph D, as well as a
      surprising increase of associated 5S rDNA/Rex3 loci, in contrast to karyomorph A.
      In this sense, E. erythrinus emerges as an excellent model system for better
      understanding the evolutionary mechanisms underlying the huge genome diversity in
      fish. This organism can also contribute to understanding vertebrate genome
      evolution as a whole.

PMID- 20815942
TI  - Molecular mechanistic associations of human diseases.
AB  - BACKGROUND: The study of relationships between human diseases provides new
      possibilities for biomedical research. Recent achievements on human genetic
      diseases have stimulated interest to derive methods to identify disease
      associations in order to gain further insight into the network of human diseases
      and to predict disease genes. RESULTS: Using about 10000 manually collected
      causal disease/gene associations, we developed a statistical approach to infer
      meaningful associations between human morbidities. The derived method clustered
      cardiometabolic and endocrine disorders, immune system-related diseases, solid
      tissue neoplasms and neurodegenerative pathologies into prominent disease groups.
      Analysis of biological functions confirmed characteristic features of
      corresponding disease clusters. Inference of disease associations was further
      employed as a starting point for prediction of disease genes. Efforts were made
      to underpin the validity of results by relevant literature evidence.
      Interestingly, many inferred disease relationships correspond to known clinical
      associations and comorbidities, and several predicted disease genes were subjects
      of therapeutic target research. CONCLUSIONS: Causal molecular mechanisms present
      a unifying principle to derive methods for disease classification, analysis of
      clinical disorder associations, and prediction of disease genes. According to the
      definition of causal disease genes applied in this study, these results are not
      restricted to genetic disease/gene relationships. This may be particularly useful
      for the study of long-term or chronic illnesses, where pathological derangement
      due to environmental or as part of sequel conditions is of importance and may not
      be fully explained by genetic background.

PMID- 20815939
TI  - Early identification and delay to treatment in myocardial infarction and stroke:
      differences and similarities.
AB  - BACKGROUND: The two major complications of atherosclerosis are acute myocardial
      infarction (AMI) and acute ischemic stroke. Both are life-threatening conditions
      characterised by the abrupt cessation of blood flow to respective organs,
      resulting in an infarction. Depending on the extent of the infarction, loss of
      organ function varies considerably. In both conditions, it is possible to limit
      the extent of infarction with early intervention. In both conditions, minutes
      count. This article aims to describe differences and similarities with regard to
      the way patients, bystanders and health care providers act in the acute phase of
      the two diseases with the emphasis on the pre-hospital phase. METHOD: A
      literature search was performed on the PubMed, Embase (Ovid SP) and Cochrane
      Library databases. RESULTS: In both conditions, symptoms vary considerably.
      Patients appear to suspect AMI more frequently than stroke and, in the former,
      there is a gender gap (men suspect AMI more frequently than women).With regard to
      detection of AMI and stroke at dispatch centre and in Emergency Medical Service
      (EMS) there is room for improvement in both conditions. The use of EMS appears to
      be higher in stroke but the overall delay to hospital admission is shorter in
      AMI. In both conditions, the fast track concept has been shown to influence the
      delay to treatment considerably. In terms of diagnostic evaluation by the EMS,
      more supported instruments are available in AMI than in stroke. Knowledge of the
      importance of early treatment has been reported to influence delays in both AMI
      and stroke. CONCLUSION: Both in AMI and stroke minutes count and therefore the
      fast track concept has been introduced. Time to treatment still appears to be
      longer in stroke than in AMI. In the future improvement in the early detection as
      well as further shortening to start of treatment will be in focus in both
      conditions. A collaboration between cardiologists and neurologists and also
      between pre-hospital and in-hospital care might be fruitful.

PMID- 20815943
TI  - Distinct alpha subunit variations of the hypothalamic GABAA receptor triplets
      (alphabetagamma) are linked to hibernating state in hamsters.
AB  - BACKGROUND: The structural arrangement of the gamma-aminobutyric acid type A
      receptor (GABAAR) is known to be crucial for the maintenance of cerebral
      dependent homeostatic mechanisms during the promotion of highly adaptive
      neurophysiological events of the permissive hibernating rodent, i.e the Syrian
      golden hamster. In this study, in vitro quantitative autoradiography and in situ
      hybridization were assessed in major hypothalamic nuclei. Reverse Transcription
      Reaction-Polymerase chain reaction (RT-PCR) tests were performed for specific
      GABAAR receptor subunit gene primers synthases of non-hibernating (NHIB) and
      hibernating (HIB) hamsters. Attempts were made to identify the type of
      alphabetagamma subunit combinations operating during the switching ON/OFF of
      neuronal activities in some hypothalamic nuclei of hibernators. RESULTS: Both
      autoradiography and molecular analysis supplied distinct expression patterns of
      all alpha subunits considered as shown by a strong (p < 0.01) prevalence of
      alpha1 ratio (over total alpha subunits considered in the present study) in the
      medial preoptic area (MPOA) and arcuate nucleus (Arc) of NHIBs with respect to
      HIBs. At the same time alpha2 subunit levels proved to be typical of
      periventricular nucleus (Pe) and Arc of HIB, while strong alpha4 expression
      levels were detected during awakening state in the key circadian hypothalamic
      station, i.e. the suprachiasmatic nucleus (Sch; 60%). Regarding the other two
      subunits (beta and gamma), elevated beta3 and gamma3 mRNAs levels mostly
      characterized MPOA of HIBs, while prevalently elevated expression concentrations
      of the same subunits were also typical of Sch, even though this time during the
      awakening state. In the case of Arc, notably elevated levels were obtained for
      beta3 and gamma2 during hibernating conditions. CONCLUSION: We conclude that
      different alphabetagamma subunits are operating as major elements either at the
      onset of torpor or during induction of the arousal state in the Syrian golden
      hamster. The identification of a brain regional distribution pattern of distinct
      GABAAR subunit combinations may prove to be very useful for highlighting
      GABAergic mechanisms functioning at least during the different physiological
      states of hibernators and this may have interesting therapeutic bearings on
      neurological sleeping disorders.

PMID- 20815945
TI  - Current status of natural orifice trans-endoscopic surgery (NOTES) and
      laparoendoscopic single site surgery (LESS) in urologic surgery.
AB  - Laparoendoscopic single site surgery (LESS) and natural orifice transluminal
      endoscopic surgery (NOTES) represent novel approaches in urological surgery. To
      perform a review of the literature in order describe the current status of LESS
      and NOTES in Urology. References for this manuscript were obtained by performing
      a review of the available literature in PubMed from 01-01-02 to 15-05-09. Search
      terms included single port, single site, NOTES, LESS and single incision. A total
      of 412 manuscripts were initially identified. Out of these, 64 manuscripts were
      selected based in their urological content. The manuscript features subheadings
      for experimental and clinical studies, as NOTES-LESS is a new surgical technique
      and its future evolution will probably rely in initial verified feasibility. A
      subheading for reviews presents information regarding common language and
      consensus for the techniques. The issue of complications published in clinical
      series and the future needs of NOTES-LESS, are also presented.

PMID- 20815946
TI  - Prostatic atrophy. Clinicopathological significance.
AB  - Prostatic atrophy is a benign lesion that may mimic adenocarcinoma histologically
      and on imaging. It is more frequent in the peripheral zone and has gained
      importance with the increasing use of needle biopsies. Diffuse atrophy occurs
      secondarily to radiotherapy and/or endocrine therapy. Inflammation and/or chronic
      local ischemia may cause focal atrophy with an increasing frequency in age.
      Atrophy may be classified morphologically into diffuse and focal. The latter may
      be partial, complete or combined. Partial focal atrophy is the most frequent
      mimicker of adenocarcinoma on needle biopsies. Complete focal atrophy may be
      subtyped into simple, sclerotic and hyperplastic (or postatrophic hyperplasia).
      Combined lesions are frequent and partial atrophy may precede complete atrophy.
      The several morphologic types of focal atrophy may represent a morphologic
      continuum and the hyperplastic (or postatrophic hyperplasia) subtype seems to be
      at the extreme end of this continuum. Chronic inflammation associated to focal
      atrophy (proliferative inflammatory atrophy) has been linked to high-grade
      prostatic intraepithelial neoplasia and/or carcinoma. This link, however, remains
      controversial in the literature. The question whether inflammation directly
      produces tissue damage and atrophy or some other insult induces atrophy directly,
      with inflammation occurring secondarily, is still unresolved. An intriguing
      finding that needs further studies is a possible association of extent of atrophy
      to serum PSA elevation.

PMID- 20815947
TI  - Gene expression profile of renal cell carcinoma clear cell type.
AB  - PURPOSE: The determination of prognosis in patients with renal cell carcinoma
      (RCC) is based, classically, on stage and histopathological aspects. The
      metastatic disease develops in one third of patients after surgery, even in
      localized tumors. There are few options for treating those patients, and even the
      new target designed drugs have shown low rates of success in controlling disease
      progression. Few studies used high throughput genomic analysis in renal cell
      carcinoma for determination of prognosis. This study is focused on the
      identification of gene expression signatures in tissues of low-risk, high-risk
      and metastatic RCC clear cell type (RCC-CCT). MATERIALS AND METHODS: We analyzed
      the expression of approximately 55,000 distinct transcripts using the Whole
      Genome microarray platform hybridized with RNA extracted from 19 patients
      submitted to surgery to treat RCC-CCT with different clinical outcomes. They were
      divided into three groups (1) low risk, characterized by pT1, Fuhrman grade 1 or
      2, no microvascular invasion RCC; (2) high risk, pT2-3, Fuhrman grade 3 or 4
      with, necrosis and microvascular invasion present and (3) metastatic RCC-CCT.
      Normal renal tissue was used as control. RESULTS: After comparison of
      differentially expressed genes among low-risk, high-risk and metastatic groups,
      we identified a group of common genes characterizing metastatic disease. Among
      them Interleukin-8 and Heat shock protein 70 were over-expressed in metastasis
      and validated by real-time polymerase chain reaction. CONCLUSION: These findings
      can be used as a starting point to generate molecular markers of RCC-CCT as well
      as a target for the development of innovative therapies.

PMID- 20815948
TI  - Endourological management of forgotten encrusted ureteral stents.
AB  - PURPOSE: To present our experience and discuss the various endourological
      approaches for treating forgotten encrusted ureteral stents associated with stone
      formation. MATERIALS AND METHODS: From July 2006 to December 2008, 14 patients
      (11 men and 3 women) with encrusted ureteral stents were analyzed. The average
      indwelling time of the stent was 4.9 years (range 1 to 12). Plain-film
      radiography was used to evaluate encrustation, stone burden, and fragmentation of
      the stents. Intravenous urogram and a Tc99m diethylene triamine penta acetic-acid
      renogram was used to assess renal function. RESULTS: In seven patients, the
      entire stent was encrusted, in three patients the encrustation was confined to
      the ureteral and lower coil part of the stent, two patients had encrustation of
      the lower coil, and minimal encrustation was observed in two patients.
      Percutaneous nephrolithotomy was performed in 5 cases and retrograde ureteroscopy
      with intra-corporeal lithotripsy in 9 patients. Cystolithotripsy was used to
      manage the distal coil of the encrusted stent in eight patients. Simple
      cystoscopic removal of the stents with minimal encrustation was carried-out in
      two cases. Looposcopy and removal of the stent was performed in one patient with
      an ileal conduit and retained stent. Only one patient required open surgical
      removal of the stent. Thirteen out of 14 patients were rendered stone and stent
      free in one session. All except two stents were removed intact and stone analysis
      of encrustation and calcification revealed calcium oxalate and calcium phosphate
      in the majority of the cases. CONCLUSION: Endourological management of forgotten
      encrusted stents is highly successful and often avoids the need for open surgical
      techniques.

PMID- 20815949
TI  - Vascular endothelial growth factor (VEGF) and prostate pathology.
AB  - PURPOSE: Previous studies suggest that vascular endothelial growth factor (VEGF)
      circulating levels might improve identification of patients with prostate cancer
      but results are conflicting. Our aim was to compare serum VEGF levels across
      different prostate pathologies (including benign prostatic hyperplasia,
      prostatitis, high grade prostate intraepithelial neoplasia and prostate cancer)
      in patients at high risk of prostate cancer. MATERIALS AND METHODS: We
      consecutively enrolled 186 subjects with abnormal digital rectal examination
      and/or total PSA (tPSA) > or = 2.5 ng/mL. Blood was collected before diagnostic
      ultrasound guided trans-rectal prostate biopsy, or any prostate oncology
      treatment, to measure PSA isoforms and VEGF. Unconditional logistic regression
      was used to compute age-, tPSA- and free/total PSA-adjusted odds ratios (OR) and
      respective 95% confidence intervals (95% CI) for the association between serum
      VEGF and different prostatic pathologies. RESULTS: Prostate biopsy main diagnoses
      were normal or benign prostatic hyperplasia (27.3%), prostatitis (16.6%), and
      prostatic cancer (55.0%). The median VEGF levels (ng/mL) in these groups were
      178.2, 261.3 and 266.4 (p = 0.029), respectively, but no significant differences
      were observed for benign vs. malignant pathologies (215.2 vs. 266.4, p = 0.551).
      No independent association was observed between VEGF (3rd vs. 1st third) and
      prostate cancer, when compared to benign conditions (adjusted OR = 1.44; CI 95%:
      0.64-3.26). CONCLUSIONS: In patients at high risk of prostate cancer, circulating
      VEGF levels have no clinical role in deciding which patients should be submitted
      to prostate biopsy. Prostatitis patients, often with higher PSA levels, also
      present high serum levels of VEGF, and their inclusion in control groups might
      explain the heterogeneous results in previous studies.

PMID- 20815950
TI  - Does tumor extent on needle prostatic biopsies influence the value of perineural
      invasion to predict pathologic stage > T2 in radical prostatectomies?
AB  - PURPOSE: Perineural invasion (PNI) on needle prostatic biopsies (NPB) has been
      controversial as a marker of extraprostatic extension and consequently for
      planning of nerve-sparing radical prostatectomy (RP). The aim of this study was
      to find whether tumor extent on NPB influences the value of PNI to predict stage
      > pT2 on RP. MATERIALS AND METHODS: This retrospective study was based on 264
      consecutive patients submitted to radical retropubic prostatectomy. Their NPB
      were matched with whole-mount processed and totally embedded surgical specimens.
      Tumor extent on NPB was evaluated as the percentage of linear tissue in mm
      containing carcinoma in all cores. Considering the median value, patients were
      stratified into 2 groups: harboring less or more extensive tumors on NPB.
      Univariate and multivariate logistic regression analyses were used to relate
      stage > pT2 to PNI and other clinical and pathological variables. RESULTS: In
      patients with more extensive tumors, PNI was predictive of stage > pT2 in
      univariate analysis but not in multivariate analysis. In less extensive tumors,
      PNI showed no association between any clinical or pathological variables studied;
      no difference in the time to biochemical progression-free status compared to
      patients without PNI; and, no predictive value for pathological stage > pT2 on
      both univariate and multivariate analyses. CONCLUSION: Tumor extent on NPB
      influences the predictive value of PNI for pathologic stage > pT2 on RP. With a
      higher number of small tumors currently detected, there is no evidence that
      perineural invasion should influence the decision on preservation of the nerve
      during radical prostatectomy.

PMID- 20815951
TI  - Transperitoneal versus extraperitoneal laparoscopic radical prostatectomy during
      the learning curve: does the surgical approach affect the complication rate?
AB  - PURPOSE: To compare the perioperative complication rate obtained with the
      transperitoneal laparoscopic radical prostatectomy (TLRP) and with the
      extraperitoneal LRP (ELRP) during the learning curve (LC). MATERIALS AND METHODS:
      Data of the initial 40 TLRP (Group 1) were retrospectively compared with the
      initial 40 ELRP (Group 2). Each Group of patients was operated by two different
      surgeons. RESULTS: The overall surgical time (175 min x 267.6 min; p < 0.001) and
      estimated blood loss (177.5 mL x 292.4 mL; p < 0.001) were statistically better
      in the Group 1. Two intraoperative complications were observed in Group 1 (5%)
      represented by one case of bleeding and one case of rectal injury, whereas four
      complications (10%) were observed in Group 2, represented by two cases of
      bleeding, one bladder and one rectal injuries (p = 0.675). Open conversion
      occurred once in each Group (2.5%). Overall postoperative complications were
      similar (52.5% x 35%; p = 0.365). Major early postoperative complications
      occurred in three and in one case in Group 1 and 2, respectively. Group 1 had two
      peritonitis (fecal and urinary), leading to one death in this group. CONCLUSIONS:
      No statistical differences in overall complication rates were observed. The
      transperitoneal approach presented more serious complications during the early
      postoperative time and this fact is attributed to the potential chance of
      intraperitoneal peritonitis not observed with the extraperitoneal route.

PMID- 20815952
TI  - Cross-cultural adaptation of the dysfunctional voiding score symptom (DVSS)
      questionnaire for Brazilian children.
AB  - PURPOSE: To translate and culturally adapt the Dysfunctional Voiding Symptom
      Score (DVSS), questionnaire into Brazilian Portuguese. MATERIALS AND METHODS: The
      10-item Dysfunctional Voiding Symptom Score (DVSS) was translated into Brazilian
      Portuguese according to a standard methodology: translation, synthesis, back
      translation, Expert Committee, and pre-testing. After the translation process the
      final version was pre-tested and patient responses were analyzed to identify
      necessary modifications. Reliability was evaluated using the test-retest method,
      and internal consistency was assessed using Cronbach's alpha. RESULTS: The
      Cronbach's alpha coefficient was calculated in the test and retest phases.
      Internal consistency was found to be satisfactory, as confirmed by a Cronbach's
      alpha coefficient of 0.76 for the test and 0.77 for the retest. A high degree of
      stability was found in the test/retest, with an intraclass correlation
      coefficient (ICC) of 0.960 (p < 0.001; 95% CI: 0.943-0.972). CONCLUSIONS: The
      cross-cultural adaptation process of the Dysfunctional Voiding Symptom Score
      questionnaire to be used on Brazilian children was successfully completed
      following internationally accepted methodologies.

PMID- 20815953
TI  - Urinary proteomics evaluation in interstitial cystitis/painful bladder syndrome:
      a pilot study.
AB  - PURPOSE: Interstitial cystitis/painful bladder syndrome (IC/PBS) is characterized
      by chronic pain, pressure and discomfort felt in the pelvis or bladder. An in
      depth shotgun proteomics study was carried out to profile the urinary proteome of
      women with IC/PBS to identify possible specific proteins and networks associated
      with IC%PBS. MATERIALS AND METHODS: Urine samples from ten female IC/PBS patients
      and ten female asymptomatic, healthy control subjects were analyzed in
      quadruplicate by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on a
      hybrid linear ion trap-orbitrap mass spectrometer. Gas-phase fractionation (GPF)
      was used to enhance protein identification. Differences in protein quantity were
      determined by peptide spectral counting. RESULTS: alpha-1B-glycoprotein (A1BG)
      and orosomucoid-1 (ORM1) were detected in all IC%PBS patients, and > or = 60% of
      these patients had elevated expression of these two proteins compared to control
      subjects. Transthyretin (TTR) and hemopexin (HPX) were detected in all control
      individuals, but > or = 60% of the IC/PBS patients had decreased expression
      levels of these two proteins. Enrichment functional analysis showed cell adhesion
      and response to stimuli were down-regulated whereas response to inflammation,
      wounding, and tissue degradation were up-regulated in IC/PBS. Activation of
      neurophysiological processes in synaptic inhibition, and lack of DNA damage
      repair may also be key components of IC%PBS. CONCLUSION: There are qualitative
      and quantitative differences between the urinary proteomes of women with and
      without IC%PBS. We identified a number of proteins as well as pathways%networks
      that might contribute to the pathology of IC%PBS or result from perturbations
      induced by this condition.

PMID- 20815954
TI  - Diminution of oxalate induced renal tubular epithelial cell injury and inhibition
      of calcium oxalate crystallization in vitro by aqueous extract of Tribulus
      terrestris.
AB  - PURPOSE: Recurrence and persistent side effects of present day treatment for
      urolithiasis restrict their use, so an alternate solution, using phytotherapy is
      being sought. The present study attempted to evaluate the antilithiatic
      properties of Tribulus terrestris commonly called as "gokhru" which is often used
      in ayurveda to treat various urinary diseases including urolithiasis. MATERIALS
      AND METHODS: The activity of Tribulus terrestris was investigated on nucleation
      and the growth of the calcium oxalate (CaOx) crystals as well as on oxalate
      induced cell injury of NRK 52E renal epithelial cells. RESULTS: Tribulus
      terrestris extract exhibited a concentration dependent inhibition of nucleation
      and the growth of CaOx crystals. When NRK-52E cells were injured by exposure to
      oxalate for 72 h, Tribulus terrestris extract prevented the injury in a dose
      dependent manner. On treatment with the different concentrations of the plant,
      the cell viability increased and lactate dehydrogenase release decreased in a
      concentration dependent manner. CONCLUSION: The current data suggests that
      Tribulus terrestris extract not only has a potential to inhibit nucleation and
      the growth of the CaOx crystals but also has a cytoprotective role. Our results
      indicate that it could be a potential candidate for phytotherapy against
      urolithiasis.

PMID- 20815955
TI  - Experimental model of human corpus cavernosum smooth muscle relaxation.
AB  - PURPOSE: To describe a technique for en bloc harvesting of the corpus cavernosum,
      cavernous artery and urethra from transplant organ donors and contraction
      relaxation experiments with corpus cavernosum smooth muscle. MATERIALS AND
      METHODS: The corpus cavernosum was dissected to the point of attachment with the
      crus penis. A 3 cm segment (corpus cavernosum and urethra) was isolated and
      placed in ice-cold sterile transportation buffer. Under magnification, the
      cavernous artery was dissected. Thus, 2 cm fragments of cavernous artery and
      corpus cavernosum were obtained. Strips measuring 3 x 3 x 8 mm(3) were then
      mounted vertically in an isolated organ bath device. Contractions were measured
      isometrically with a Narco-Biosystems force displacement transducer (model F-60,
      Narco-Biosystems, Houston, TX, USA) and recorded on a 4-channel Narco-Biosystems
      desk model polygraph. RESULTS: Phenylephrine (1 microM) was used to induce tonic
      contractions in the corpus cavernosum (3-5 g tension) and cavernous artery (0.5-1
      g tension) until reaching a plateau. After precontraction, smooth muscle
      relaxants were used to produce relaxation-response curves (10(-12) M to 10(-4)
      M). Sodium nitroprusside was used as a relaxation control. CONCLUSION: The
      harvesting technique and the smooth muscle contraction-relaxation model described
      in this study were shown to be useful instruments in the search for new drugs for
      the treatment of human erectile dysfunction.

PMID- 20815956
TI  - Re: Safety of ultrasound-guided transrectal extended prostate biopsy in patients
      receiving low-dose aspirin.

PMID- 20815973
TI  - Food nutrition labelling practice in China.
AB  - OBJECTIVE: The present study aimed to scrutinize the food nutrition labelling
      practice in China before the Chinese Food Nutrition Labeling Regulation (CFNLR)
      era. DESIGN: Nutrition information of pre-packaged foods collected from a
      supermarket between December 2007 and January 2008 was analysed and compared with
      findings from a survey conducted in Beijing. SETTING: Information collected from
      a supermarket in Shanghai. SUBJECTS: A total of 850 pre-packaged foods. RESULTS:
      In the Shanghai survey, the overall labelling rate was 30.9 %, similar to that
      found in the Beijing study (29.7 %). While only 20.5 % of the snacks in Shanghai
      had nutrition labelling, the percentage of food items labelled with SFA (8.6 %),
      trans fatty acid (4.7 %) or fibre (12.1 %) was very low. Of those food items with
      nutrition labels, a considerable proportion (7-15 %) did not label energy, fat,
      carbohydrate or protein. Food products manufactured by Taiwan and Hong Kong
      companies had a lower labelling rate (13.6 %) than those manufactured by domestic
      (31.6 %) or international manufacturers (33.8 %). CONCLUSIONS: The very low food
      nutrition labelling rate among products sold in large chain supermarkets in major
      cities of China before CFNLR emphasizes the need for such critical regulations to
      be implemented in order to reinforce industrial compliance with accurate
      nutrition labelling.

PMID- 20815974
TI  - Rostellar hook morphology of larval Echinococcus granulosus isolates from the
      Indian buffalo and Iranian sheep, cattle and camel.
AB  - Isolates of Echinococcus granulosus from the Indian buffalo and Iranian sheep,
      cattle and camels were characterized on the basis of rostellar hook morphology of
      the protoscolices. Results obtained indicated phenotypic polymorphism among
      parasites isolated from different host species. Isolates from buffalo are
      morphologically quite different from those of the more common sheep and cattle
      isolates and may represent a different strain, adapted to buffalo. In the Sari
      region of northern Iran, two morphologically distinct forms of E. granulosus, one
      in sheep and one in camels, were identified. Total length and handle length of
      both large and small hooks were considered the most variable characteristics
      which could be used not only for differentiating parasite isolates from different
      host species but also the origin of infection in the definitive host. We
      therefore suggest that larval hook morphology may be considered as a valid
      criterion for the identification of E. granulosus strains in Iran.

PMID- 20815975
TI  - Effects of Lactobacillus acidophilus NCFM on insulin sensitivity and the systemic
      inflammatory response in human subjects.
AB  - According to animal studies, intake of probiotic bacteria may improve glucose
      homeostasis. We hypothesised that probiotic bacteria improve insulin sensitivity
      by attenuating systemic inflammation. Therefore, the effects of oral
      supplementation with the probiotic bacterium Lactobacillus acidophilus NCFM on
      insulin sensitivity and the inflammatory response were investigated in subjects
      with normal or impaired insulin sensitivity. In a double-blinded, randomised
      fashion, forty-five males with type 2 diabetes, impaired or normal glucose
      tolerance were enrolled and allocated to a 4-week treatment course with either L.
      acidophilus NCFM or placebo. L. acidophilus was detected in stool samples by
      denaturating gradient gel electrophoresis and real-time PCR. Separated by the 4
      week intervention period, two hyperinsulinaemic-euglycaemic clamps were performed
      to estimate insulin sensitivity. Furthermore, the systemic inflammatory response
      was evaluated by subjecting the participants to Escherichia coli
      lipopolysaccharide injection (0.3 ng/kg) before and after the treatment course.
      L. acidophilus NCFM was detected in 75 % of the faecal samples after treatment
      with the probiotic bacterium. Insulin sensitivity was preserved among volunteers
      in the L. acidophilus NCFM group, whereas it decreased in the placebo group. Both
      baseline inflammatory markers and the systemic inflammatory response were,
      however, unaffected by the intervention. In conclusion, intake of L. acidophilus
      NCFM for 4 weeks preserved insulin sensitivity compared with placebo, but did not
      affect the systemic inflammatory response.

PMID- 20815976
TI  - Total flavonoid fraction of the Herba epimedii extract suppresses urinary calcium
      excretion and improves bone properties in ovariectomised mice.
AB  - Flavonoids are the active components of Herba epimedii (HEP), a commonly used
      herb for the management of osteoporosis in China over the centuries. The present
      study aims to characterise the in vivo effects of its total flavonoid (TF)
      fraction on bone properties and mineral metabolism as well as to study the
      mechanism involved in achieving its protective effects against ovariectomy (OVX)
      induced bone loss. TF suppressed OVX-induced increase in urinary Ca excretion as
      well as loss of bone mass and strength at the distal femur in mice in a dose
      dependent manner. The changes in urinary Ca excretion were inversely correlated
      with the expressions of renal Ca transport protein (CaBP-28K) and vitamin D
      receptor mRNA in OVX mice. TF (100 MUg/g) treatment prevented the deterioration
      of trabecular bone microarchitecture induced by OVX in mice. In addition, TF
      treatment increased the expression of type I collagen and osteocalcin mRNA and
      the ratio of osteoprotegerin/receptor activator of NF-kappaB ligand mRNA, and
      suppressed the increase in IL-6 mRNA induced by OVX in the femur of mice. The
      present results indicate that the optimal dosage of the TF fraction of HEP for
      the improvement of bone properties and mineral metabolism in OVX mice was between
      50 and 100 MUg/g. Mechanistic studies indicated that TF might increase renal Ca
      reabsorption, stimulate the process of osteoblast formation as well as suppress
      the process of osteoclastogenesis in OVX mice.

PMID- 20815977
TI  - [Changes of Foxp3 and IL-10 and TGF-beta in aging of mice].
AB  - AIM: To compare the expression levels of Foxp3 mRNA in the spleen PBMC
      (peripheral blood mononuclear cell) in the progress of aging mice and analyse the
      relevance with serum IL-10 and TGF-beta. METHODS: Healthy male BALB/c mice were
      divided into 3 groups at random (8 mice each group): 2m group with 2 months mice
      (young), 6m group with 6 months mice (middle-aged) and 15m group with 15 months
      mice (aged). The phenotype of CD4(+);CD25(+);Foxp3(+); T cells derived from
      normal murine SPL were analyzed by FCM. Real-time fluorescence quantitative RT
      PCR was used to determine the expression levels of Foxp3 mRNA in the spleen PBMC.
      ELISA was used to detect the concentration of IL-10 and TGF-beta. RESULTS: The
      subsets of CD4(+);CD25(+);Foxp3(+); T lymphocytes from murine splenocytes were
      significantly higher in 15m group than that in 2m group(P<0.01). The expression
      levels of Foxp3 mRNA in the spleen PBMC were significantly higher in 15m group
      than that in 2m group(P<0.01).The serum concentration of IL-10 and TGF-beta were
      significantly higher in 15m group than that in 2m group(P<0.01).There was no
      correlation between serum concentration of IL-10 and TGF-beta and Foxp3 mRNA
      expression levels in the spleen PBMC in 15m group. CONCLUSION: The level of the
      CD4(+);CD25(+);Foxp3(+); T cells and Foxp3 mRNA expression levels were up
      regulated and IL-10 and TGF-beta contents were increased in the progress of aging
      mice. Foxp3 and IL-10 and TGF-beta may be play a part in the process of
      immunosenescence. Quantitative detection of Foxp3 mRNA by the method of SYBR
      Green I real-time fluorescence quantitative RT-PCR is stable and reliable.

PMID- 20815978
TI  - [Effects of delta1 gene transfection on biological behaviors of rat dendritic
      cells].
AB  - AIM: To explore the effects of Delta1 gene on rat bone marrow-derived dendritic
      cells (DCs). METHODS: pcDNA3.1/delta1 plasmid was transfected into Rat DCs with
      lipofectamine gene transfection method. The expression of activation markers(Iad,
      CD80 and CD86) were examined by flow cytometry, the release of cytokines IL-12
      were examined by ELISA and the stimulatory capacity of the resulting DCs in vitro
      were examined by mixed lymphocyte reaction(MLR). RESULTS: The biological
      character of DCs in experimental group, empty vector group and control group were
      examined by electron microscope, flow cytometry and cell growth rate counting.
      There were no differences of cell cycles, ultrastructure and cell growth rate
      among these three group cells (P>0.05). It stated that delta1 gene had no effect
      on the growth of DCs. Even at the stimulation of LPS, In the delta1 transfected
      DCs, we observed no significant effects on the expression of activation
      markers(Iad, CD80 or CD86). The release of IL-12 in DCs/delta1 was reduced
      compared with control DCs(P<0.05). The levels of IFN-gamma and IL-2 of the
      DCs/delta1 were significantly lower than those of the DCs(P<0.05), and the levels
      of IL-4 and IL-10 were significantly higher than that in control DCs(P<0.05).
      CONCLUSION: Our data demonstrates that the delta1 gene transfection does not
      interfere with the differentiation or maturation of DCs, but reduce the ability
      to stimulating T cells, and the mechanism may be related to the decrease of Th1
      /Th2 ratio by impairing the production of DCs-derived IL-12.

PMID- 20815979
TI  - [Comparison the inhibitory effects of human bone marrow mesenchymal stem cells
      and human placenta mesenchymal stem cells on T cell proliferation].
AB  - AIM: To compare and study the inhibitory effects of human bone marrow mesenchymal
      stem cells (HBMSCs) and human palacenta mesenchymal stem cells (HPMSCs) on T cell
      proliferation, and the underlying mechanism. METHODS: The expression of B7H4 on
      HBMSCs or the expression of PDL1 on HPMSCs were detected by FCM. Blocking
      experiment was used to analyze the effects of B7H4 or PDL1 on HBMSCs or HPMSCs
      mediating suppression on T cell proliferation and cell cycle. RESULTS: FCM
      detection showed that HBMSCs highly expressed B7H4, while HPMSCs highly expressed
      PDL1, the negative immune molecules. Blockade B7H4 on HBMSCs with B7H4mAb
      significantly attenuated the inhibitory effects of HBMSCs on T cell
      proliferation. Likewise, blocking the expression of PDL1 on HPMSCs obviously
      weakened the suppressive effects of HPMSCs on T cell proliferation activated by
      PHA. Moreover, Blockade B7H4 on HBMSCs with B7H4mAb or PDL1 on HPMSCs with
      PDL1mAb significantly weakened the inhibitory effects of HBMSCs or HPMSCs on T
      cell cycle through down-regulating the cell number in G(0);/G(1); phase and up
      regulating the cell number in S phase. CONCLUSION: HBMSCs and HPMSCs could
      mediate the suppressive effects on T cell proliferation through expressing
      different negative immune molecules.

PMID- 20815980
TI  - [Construction of eukaryotic expression vector of mTSARG3 and establishment of its
      stable transfected cell line].
AB  - AIM: To study the function of mTSARG3, the eukaryotic expression vector of mouse
      mTSARG3 and its stable transfected GC-1 cell line was established. METHODS: The
      open reading frame (ORF) of mTSARG3 was amplified from mouse testis cDNA library
      by PCR. The products were cloned into pGEM-T Easy vectors and sequenced. Then the
      recombinant plasmid was digested by Not I and Hind III. The target cDNA fragment
      was subcloned into pcDNA3.1 Hygro(-), a eukaryotic expression vector. The
      recombined plasmid pcDNA3.1 Hygro(-)/mTSARG3 was identified and transfected into
      GC-1 spg cell. After screening culture by hygromycin, stable transfected GC-1
      cell line was established, and the expression of mTSARG3 was identified by RT-PCR
      and Western blot. The flow cytometry was adopted to observe the influence on cell
      cycle, and the apoptosis of GC-1 cells transfected with pcDNA3.1 Hygro(-)/mTSARG3
      and pcDNA3.1 Hygro(-), respectively. RESULTS: The eukaryotic expression plasmid
      of pcDNA3.1 Hygro(-)/mTSARG3 was successfully constructed and stable transfected
      GC-1 cell line was established. RT-PCR and Western blot result revealed that
      mTSARG3 was expressed successfully in GC-1 cells. The flow cytometer shows that
      the cell transfected with pcDNA3.1 Hygro(-)/mTSARG3 could accelerate the growth
      and reduce the apoptosis of GC-1 cells. CONCLUSION: The recombinant eukaryotic
      expression vector of pcDNA3.1 Hygro(-)/mTSARG3 has been constructed successfully
      and stably expressed in GC-1 cell line. The establishment of mTSARG3 stable
      transfected GC-1 spg cell line will provide a foundation for further studies on
      the function of mTSARG3 in vitro.

PMID- 20815981
TI  - [Effect of down-regulation of Id3 expression by microRNA on proliferation and
      apoptosis of A549 cells].
AB  - AIM: To investigate the effect of microRNA-mediated exogenous Id3 gene silencing
      on proliferation and apoptosis of human lung adenocarcinoma A549 cells in vitro.
      METHODS: A recombinant miRNA expression vector (pcDNA6.2-GW/EmGFPmiR-Id3,
      pcDNA/miRId3) which targets human Id3 gene was constructed. After 24 h of
      transfection, the transfection efficiency was monitored by inverted fluorescence
      microscopy.EGFP expression efficiency in A549 cells was analyzed by flow
      cytometry (FCM).Id3 expression vector pEGFP/Id3 and pcDNA/miRId3 were
      cotransfected into A549 cells by liposome-mediated method. After 24 h of
      transfection, the transfection efficiency was monitored by inverted fluorescence
      microscopy.Semi-quantitative RT-PCR and Western blot were used for identifying
      Id3 mRNA and protein expression respectively in A549 cells after transfection.
      Cell proliferation rate and apoptosis ratio were evaluated by MTT assay and
      Annexin V/7-ADD staining followed by FCM to observe the down-regulatory effect of
      Id3 expression by miRNA-mediated RNA interference (RNAi). RESULTS: pcDNA/miRId3
      and pEGFP/Id3 were successfully transfected into A549 cells. RT-PCR and Western
      blot results showed that after 24 h of cotransfection of pEGFP/Id3 and
      pcDNA/miRId3 in A549 cells, the exogenous expression of Id3 both at mRNA and
      protein levels were significantly reduced compared with the pEGFP/Id3 group. MTT
      assay and Annexin V/7-AAD staining showed that after 24 h of transfection with
      pEGFP/Id3, the proliferation rates were significantly reduced and apoptotic cell
      ratios were significantly higher than those of pEGFP-transfected cells.Whereas
      there were not any significant differences in proliferation rates or apoptotic
      cell ratios between pcDNA/miRId3+pEGFP/Id3 cotransfected group and pEGFP or miRNA
      negative controls. CONCLUSION: Exogenous expression of Id3 in A549 cells could
      inhibit proliferation and induce apoptosis of A549 cells. Cotransfection of
      pcDNA/miRId3 and pEGFP/Id3 into A549 could reverse the Id3-induced proliferation
      inhibition and apoptosis. Construction and application of Id3-targeting miRNA
      expression vector may build some foundations for investigation the mechanisms of
      Id3-induced proliferation inhibition and apoptosis in A549 cells.

PMID- 20815982
TI  - [HCV DF protein inhibits expression of p16 and p21 in HepG2 cells].
AB  - AIM: To investigate the effect of HCV DF (Double-shift F) protein on the
      expression p16 and p21 in HepG(2); cells. METHODS: DF gene was amplificated from
      the whole HCV 1b genome, and cloned into pCDNA3.0 vecter. The recombinant plasmid
      (pCDNA3.0/HCV-DF) and empty vector were transfected into HepG(2); cells.
      Screening was performed with G418. p16 and p21 mRNA were detected by semi
      quantitative RT-PCR, and protein by Western blot. RESULTS: Stable expression of
      the recombinant plasmid was found in HCV DF protein. The expression of p16 and
      p21 in HepG();2 cells transfected with pCDNA3.0/HCV-DF were lower than those with
      blank plasmid. CONCLUSION: HCV DF protein inhibits expression of p16 and p21 in
      HepG(2); cells. This suggested that HCV DF protein may participate in the
      progress of hepatocellular carcinoma.

PMID- 20815983
TI  - [Preparation of rabbit antibody against human Id3 and identification of
      intracellular localization of Id3 in tumor cells].
AB  - AIM: To express and purify the recombinant human inhibitor of differentiation 3
      (Id3) in E.coli and prepare rabbit polyclonal antibody against Id3. METHODS: The
      expression vector Id3/pET32a was transformed into E.coli BL21(DE3) and expression
      of histidine (His)-tagged Id3 fusion protein was induced with IPTG and confirmed
      by SDS-PAGE and Western blot techniques. Id3 fusion protein was purified through
      immolbilized Ni(2+); absorption chromatographic column.The purified protein was
      used to immunize rabbits.The titer and specificity of rabbit antisera were
      evaluated by immunodouble gel diffusion, ELISA and Western blot techniques. The
      collected rabbit antisera were purified with polypeptide affinity column. The
      intracellular distributions of Id3 expression in human human breast cancer cells
      (MCF7), prostate cancer cells (PC-3M) and lung adenocarcinoma cells (A549) were
      observed by indirect immunofluorescence assay(IFA). RESULTS: Id3 fusion protein
      with 6xhis-tag was successfully expressed in E.coli BL 21. The expressed Id3 with
      the relative molecular mass size of 34 kD was purified specifically through
      affinity chromatographic column and confirmed by Western blot. The titers of the
      rabbit anti-Id3 polyclonal antibodies were 1:8 by immunodouble gel diffusion and
      1:8 000 by ELISA. Western blot revealed that the prepared antisera reacted
      specifically with Id3. IFA showed that in A549 , MCF7 and PC-3M cells, Id3 was
      mainly distributed in nucleoplasm and the Id3 expression level was significantly
      higher in MCF7 and PC-3M than in A549 cells. CONCLUSION: The expression and
      purification of human Id3 protein and preparation of polyclonal antibody against
      Id3 provide useful tools for the further study of Id3.

PMID- 20815984
TI  - [Preparation of PHF10 antibody and analysis of PHF10 expression gastric cancer
      tissues].
AB  - AIM: To prepare PHF10 antibody and check the expression of PHF10 protein in the
      tissues of gastric cancer and adjacent tissue. METHODS: His-tagged PHF10 was
      expressed in E.coli BL21. Rabbit PHF10 polyclonal antiserum was generated by
      injecting the purified recombinant His-tagged PHF10 inclusion body as the
      antigen, and further separated by affinity purification. To confirm the
      specificity of the PHF10 antibody, transiently expressed Flag-PHF10 fusion
      protein was analyzed by immunoblotting with anti-flag monoclonal antibody
      control. The produced antibody Was used to check the expression of PHF10 protein
      in gastric cancer and adjacent tissues by Western blot. RESULTS: Antibodies
      specifically binding to PHF10 could be obtained by immunization, and expression
      of PHF10 was significantly higher in gastric cancerous tissues comparing with
      adjacent normal tissues and GES-1 shows more PHF10 expression than gastric cancer
      cell lines with the generated antibody. CONCLUSION: The specific anti-PHF10
      antibody is obtained and it could be used to detect the expression of PHF10
      protein in gastric cancer cell lines and tissues, in which PHF10 is unregulated
      in gastric cancer.

PMID- 20815985
TI  - [IL-2 stimulated responses of CD3(+) CD56(+) NKT cells in pulmonary tuberculosis
      patients].
AB  - AIM: To observe the activation and proliferation characteristics of IL-2
      stimulated CD3(+);CD56(+); NKT cells in pulmonary tuberculosis (PTB) patients.
      METHODS: Peripheral blood mononuclear cells (PBMCs) from PTB patients and normal
      subjects were stimulated with IL-2 and cultured for different time points. The
      CD69 expression on and amount of the CD3(+);CD56(+); NKT cells were detected by
      multi fluorescence staining and flow cytometry at different time of stimulation
      and culture. RESULTS: There was no significant difference in percentage of NKT
      cells between PTB patients and normal healthy controls before culture. When IL-2
      was used to stimulate for 0 h, 8 h, 16 h, 40 h and 64 h, the expression of CD69
      on NKT cells in normal controls and PTB patients increased significantly, but the
      CD69 expression level of NKT cells in PTB patients was significantly higher than
      that in normal persons(P<0.05). In PTB patients group, PBMCs were expanded
      significantly after stimulated by IL-2, the absolute number of NKT cells
      increased from (3.44+/-1.20)x10(4); to (323.23+/-75.98) x10(4); (P<0.01),
      expanded by 108.69+/-59.22 fold, In normal control group the absolute number of
      NKT cells increased from (5.57+/-5.16)x10(4); to (1475.05+/-868.98)x10(4);
      (P<0.01), expanded by 246.26+/-134.06 fold, the expanding efficiency in PTB group
      was significantly lower than that in normal control group (P<0.05). CONCLUSION:
      NKT cells in PTB patients present with high activation but low proliferation
      after stimulated by IL-2.

PMID- 20815986
TI  - [Inhibitor of apoptosis in lung cancer Livin perioperative clinical research].
AB  - AIM: To detect the inhibitor of apoptosis protein Livin in non-small cell lung
      cancer patients with perioperative serum levels were analyzed trends in
      perioperative period to explore the Livin in non-small cell lung cancer
      diagnosis, classification and prognosis of clinical significance. METHODS: Enzyme
      linked immunosorbent assay (ELISA) of 40 patients with non-small cell lung cancer
      patients before surgery, the serum levels of Livin expression and 20 cases of
      normal healthy human serum levels of Livin were detected. RESULTS: Non-small cell
      lung cancer patients was significantly higher than the level of serum Livin
      healthy control group. Before surgery (median 526.49 ng/L, quartile 357.93-825.57
      ng/L), postoperative (median 286.49 ng/L, quartile 157.93-515.57 ng/L), there was
      significant difference between the two groups (P<0.05).Livin the average level of
      serum with non-small cell lung cancer the relationship between pathology: I, II
      period (median 326.49 ng/L, quartile 201.54-623.19 ng/L) and stage III (median
      586.31 ng/L, quartile 411.79-965.34 ng/L) statistically significant difference
      between (P<0.05); tumor lymph node metastasis in 11 cases (median 562.03 ng/L,
      quartile 382.64-982.61 ng/L) and the 29 cases without lymph node metastasis
      (median 344.59 ng/L, quartile 167.27-646.20 ng/L) significant difference between
      (P<0.05); organization credits of: high, medium, poorly differentiated among the
      three groups without significant differences (P>0.05). CONCLUSION: Livin as a new
      inhibitor of apoptosis protein in non-small cell lung cancer diagnosis, staging
      has some clinical value.

PMID- 20815988
TI  - Mindfulness-based stress reduction for people with chronic diseases.
AB  - Mindfulness-based stress reduction (MBSR) is a structured group program that uses
      mindfulness meditation to improve well-being and alleviate suffering. This
      article reviews the impact of MBSR for people with chronic diseases. The review
      includes original research that was published in English and peer-reviewed and
      reported outcomes for adults with chronic diseases who had participated in an
      MBSR program. Fifteen studies were identified. Outcomes related to mental and
      physical health, well-being, and quality of life. The studies included different
      research designs, and used self-report and physiological outcome measures.
      Participants' clinical diagnoses included fibromyalgia, chronic pain, rheumatoid
      arthritis, type 2 diabetes, chronic fatigue syndrome, multiple chemical
      sensitivity, and cardiovascular diagnoses. All 15 studies found that
      participation in an MBSR program resulted in improvements. No negative change was
      reported between baseline and follow up. Outcomes in regard to specific variables
      were difficult to compare and equivocal. Overall, positive change predominated.
      Chronic diseases are associated with a range of unwelcome psychological and
      physical consequences. Participation in an MBSR program is likely to result in
      coping better with symptoms, improved overall well-being and quality of life, and
      enhanced health outcomes. As an adjunct to standard care, MBSR has potential for
      much wider application in Australian primary care settings.

PMID- 20815987
TI  - [Clinical significance of determination of serum B7-H4 in patients with malignant
      hematologic diseases].
AB  - AIM: To study the clinical significance of determination of serum B7-H4 in
      patients with malignant hematologic diseases. METHODS: Serum B7-H4 levels were
      determined in 65 patients with leucemia, 34 patients with lymphoma, 12 patients
      with multiple myeloma as well as in 50 healthy controls. RESULTS: The serum B7-H4
      levels in patients with lymphoma [(38.81+/-10.34) kappag/L] were significantly
      higher than healthy controls [(31.62+/-9.850) kappag/L] (P<0.01). But there are
      no significant difference of B7-H4 levels in serum among patients with leucemia,
      patients with multiple myeloma and healthy controls. CONCLUSION: These results
      suggest that the B7-H4 may correlated with lymphoma, but uncorrelated with
      leucemia and multiple myeloma. Measurement of serum B7-H4 level provide useful
      information for distinctive diagnosis of different kinds of malignant hematologic
      diseases.

PMID- 20815989
TI  - Preparing nurses for primary health care futures: how well do Australian nursing
      courses perform?
AB  - Health reform is increasingly targeted towards strengthening and expansion of
      primary health systems as care is shifted from hospitals to communities. The
      renewed emphasis on prevention and health promotion is intended to curb the tide
      of chronic disease and sustain effective chronic disease management, as well as
      address health inequities and increase affordable access to services. Given the
      scope of nurses' practice, the success of Australia's health system reforms are
      dependent on a nursing workforce that is appropriately educated and prepared for
      practice in community settings. This article reports on the results of an
      Australian national audit of all undergraduate nursing curricula to examine the
      extent of professional socialisation and educational preparation of nurses for
      primary health care. The results of the audit are compared with Australian
      nursing standards associated with competency in primary health care. The findings
      indicate that Australian nursing competencies are general in their approach to
      skills and knowledge, not specifying any particular competencies for primary
      health care, while undergraduate student preparation for practice in primary
      health and community settings is patchy and not keeping pace with reform agendas
      that promote expanded roles for nurses in primary health care, prevention and
      health promotion. The implication for nursing curriculum reform is that attention
      to achieving nursing graduate capacity for primary health care and health
      promotion is a priority.

PMID- 20815990
TI  - Climate change and the possible health effects on older Australians.
AB  - Climate change is an important issue for Australia. Climate change research
      forecasts that Australia will experience accelerated warming due to anthrogenic
      activities. Australia's aging society will face special challenges that demand
      current attention. This paper discusses two issues in relation to climate change
      and older Australians: first, pharmacology and autoregulation; and second, mental
      health among older Australians.

PMID- 20815991
TI  - Evaluating the use of Enhanced Primary Care health assessments by general
      practices in North Queensland.
AB  - The Enhanced Primary Care (EPC) program funds GPs to provide preventative health
      assessments through a specific set of Medicare item numbers. The study aimed to
      show whether patients completing these health assessments had better recorded
      screening rates than those receiving usual care. A retrospective clinical record
      audit was undertaken in north Queensland general practices by practice nurses
      from the North Queensland Practice Based Research Network. Comparisons were made
      between the recorded screening test rates for patients who completed an over-75
      years health assessment with those who did not. A questionnaire was also
      completed by practice nurses and practice principals. Screening tests were
      recorded more frequently in patients with a completed health assessment: notably
      urinalysis, visual acuity and faecal occult blood test/colonoscopy. Blood
      pressure was the most frequently recorded test with or without a health
      assessment. The questionnaires provided useful information on how health
      assessments are implemented and whether GPs believe they are useful.

PMID- 20815992
TI  - Nurse-patient encounters in general practice: patterns in general practitioner
      involvement and use of nurse-specific Medicare items.
AB  - A significant gap exists in knowledge about general practice nurses' (GPNs)
      patient care activities, despite their now strong presence in Australian general
      practice. The aim of this paper is to explore the extent of direct general
      practitioner (GP) involvement in nurse-patient consultations, and to compare
      consultations where nurse-specific Medicare items were claimable with
      consultations where they were not. Data from the Practice Nurse Work Survey, a
      national cross-sectional survey conducted between May 2007 and May 2008, were
      analysed. Of the total 5253 nurse-patient encounters, 29% did not involve any
      contact between the patient and a GP, either directly before, during or directly
      after the nurse consultation. Encounters without GP involvement were more likely
      to be indirect (e.g. by telephone) and off-site (e.g. home visits), and had
      higher rates of administrative actions such as documentation and arranging
      visits. Nurse-specific Medicare item numbers applied in less than half (42%) of
      nurse-patient encounters. Encounters where no such item applied were more likely
      to involve medical examinations, blood tests, electrical tracings, physical
      function tests, removal of sutures, test results, assisting at operations and
      preparing for procedures. These results confirm that existing data collections do
      not capture the extent and nature of GPNs' clinical work.

PMID- 20815993
TI  - The photovoice method: researching the experiences of Aboriginal health workers
      through photographs.
AB  - This paper discusses the methodological framework and perspectives that were used
      in a larger study aiming at examining the experience of working life among female
      Aboriginal health care workers. Currently, the voice of Aboriginal women who work
      in the Australian health system has not received much attention. In comparison to
      other occupations and backgrounds, there is virtually no literature on Aboriginal
      woman health care workers despite 15% of health care and social service industry
      employees in Australia being Aboriginal. In this study, we selected female
      participants because of the fact that of these 15% of health workers in the
      Victorian health system, 76% of them are women. This paper outlines some of the
      barriers in researching Indigenous communities. These barriers were overcome in
      this study by framing the research in feminist theory, decolonising theory,
      empowerment and by employing the photovoice method. The photovoice method was
      used because it is relatively unobtrusive and has the capacity to be empowering.
      All data was extrapolated from the participants' own narratives that were
      prompted by the photographs they had taken. The data produced were rich
      descriptions and narratives that were oral as well as visual. Finally, the
      article discusses the experience of using the photovoice method from the
      researcher and participants' perspective.

PMID- 20815994
TI  - 'Not the full Monty': a qualitative study of seniors' perceptions of generic
      medicines in Western Australia.
AB  - The study explored consumers' perspectives on generic medicine use in Australia.
      A qualitative methodology was used to explore the topic, including community
      participation in the form of forums, focus groups and a panel of seniors. Three
      consumer forums were held from which a seniors' panel was formed and a series of
      focus groups were conducted. Participants demonstrated considerable mistrust of
      generic medicines. Participants highlighted their uncertainty about the extent of
      pharmaceutical companies' influence on health professionals, the mistrust of
      foreign generic manufacturers and scepticism in their equivalence. In addition,
      the substitution of generic medicines and variability in packaging added to the
      overall concern and reported poor compliance. Altering consumers' beliefs and
      attitudes about generic medicines might require a more concerted effort to reduce
      consumer mistrust. Consumers' beliefs about generic medicines will strongly
      affect attempts to increase generic prescribing in Australia. Many seniors
      require multiple medications for a range of chronic conditions. Currently
      however, the lack of uniformity in information and packaging implies that closer
      monitoring, greater clarity of information and improved packaging of generic
      medicines is required. Otherwise, the widespread problems and lower uptake of
      generic medicines amongst seniors will remain.

PMID- 20815995
TI  - A picture speaks a thousand words: evaluation of a pictorial post-vaccination
      care resource in Australia.
AB  - Evaluating the 'Common Reactions to Vaccination' post-vaccination care resource
      was seen as an opportunity to contribute to the limited literature base in this
      important area, learn from the strengths and weaknesses of the resource and gain
      insight into post-vaccination care practices. Semi-structured in-depth interviews
      were conducted with 12 general practitioners and 29 practice nurses in New South
      Wales and Australian Capital Territory, Australia. Structured interview guides
      were used and data was analysed thematically. A self-administered survey was also
      distributed to parents or guardians during routine childhood vaccination visits.
      When compared with previous resources, participants felt the new resource was
      more appropriate as it had a simple layout; it was colourful, incorporated
      pictures and had basic and practical information. Information about post
      vaccination care and common reactions to vaccination must be provided in written
      form accompanied by a verbal reinforcement so that patients can revisit the
      information at a later stage if required. The 'Common Reactions to Vaccination'
      post-vaccination care resource provides comprehensive information in an easy-to
      understand pictorial way and was appreciated by both vaccination providers and
      patients.

PMID- 20815996
TI  - A response to patient-initiated aggression in general practice: Australian
      professional medical organisations face a challenge.
AB  - Little is known about the incidence, prevalence, and impact of patient-initiated
      aggression against general practice staff in Australia or how medically related
      professional organisations respond to this. The few available Australian studies
      suggest that up to about two-thirds of Australian GPs experience patient
      initiated aggression within a 12-month period. This paper reports on relevant
      professional stakeholder organisations' perceptions of and response to aggression
      perpetrated against their members working in Australian general practices.
      Thirteen organisations each nominated a representative to undertake a one-off
      semi-structured interview. Respondents informed the study findings from
      organisational, practice level, and Divisions of General Practice perspectives.
      While all professional organisations were cognisant of the presence of violence
      and aggression in Australian general practice, very few offered proactive
      measures in the management of difficult or aggressive patients, or practical
      support to their members. Organisations with fewer members involved in general
      practice were overall more supportive and proactive with regard to education,
      training, and publications than were organisations with a greater proportion of
      their membership involved in general practice settings. Respondents believed the
      current socio-political climate provided opportunity for a greater organisational
      response, but there was uncertainty regarding the appropriate response in view of
      a lack of evidence base.

PMID- 20815997
TI  - Investigating referral pathways from primary care to consumer health
      organisations.
AB  - While chronic disease places an increasing burden on Australia's primary care
      system it is unrealistic to expect GPs to meet the range of support needs
      experienced by patients managing chronic conditions. Consumer health
      organisations (CHO) have the potential to augment clinical care by providing a
      variety of supportive services; however, they are underutilised by patients and
      GPs. This qualitative study investigates GPs' knowledge and perceptions of CHO
      and their contributions to chronic disease care. The study involved semi
      structured interviews with 10 GPs. Overall, participants demonstrated clear
      understanding of the role of CHO in chronic disease management, but a critical
      finding was the way GPs' view of their own chronic care role appears to influence
      referral practices. GPs operating in a traditional role were less likely to refer
      to CHO than those who had adopted a chronic care approach. A second key finding
      related to GPs' views of Diabetes Australia. All GPs identified this organisation
      as an important referral point, providing some reassurance that CHO can be
      integrated into the primary care sector. Further research is needed to determine
      how the 'definite advantages' associated with Diabetes Australia can be used to
      extend GP referral and enhance the health system's integration of other CHO.

PMID- 20815998
TI  - Family food work: lessons learned from urban Aboriginal women about nutrition
      promotion.
AB  - This article reports on ethnographic study of urban Aboriginal family food and
      implications for nutrition promotion. Data were collected over 2 years through in
      depth interviews and participant observation in groups conducted through
      Indigenous organisations in a suburb of Brisbane. Issues when organising family
      food include affordability, keeping family members satisfied and being able to
      share food, a lack of cooking ideas, the accessibility of nutrition information,
      additional work involved in ensuring healthy eating, and a desire for
      convenience. Many different health professionals provide nutrition advice, often
      directing it towards individuals and not providing adequate guidance to
      facilitate implementation. The easiest advice to implement worked from existing
      household food practices, skills and budget. Cooking workshops helped to provide
      opportunities to experiment with recommended foods so that women could
      confidently introduce them at home. Aboriginal women are concerned about healthy
      eating for their families. Disadvantage can limit dietary change and the
      complexity of family food work is often underestimated in nutrition promotion.
      Household, rather than individual, framing of nutrition promotion can lead to
      more sustainable healthy eating changes.

PMID- 20815999
TI  - Evaluation of synthesized cross linked polyvinyl alcohol as potential
      disintegrant.
AB  - PURPOSE: The present study deals with evaluation of crosslinked poly vinyl
      alcohol (PVA) as a potential disintegrant. METHODS: Crosslinking of PVA was
      carried out using glutaraldehyde as a crosslinker, in presence of acidic
      conditions. The crosslinking reaction was optimized for a) polymer: crosslinker
      ratio; b) temperature requirement and c) reaction duration. Certain physical
      parameters of the disintegrant (including sedimentation volume, hydration
      capacity, specific surface area and bulk and tap density) were determined and
      compared to the known disintegrants. Characterization was carried out using FT
      IR, DSC, XRD, SEM and Photo microscopy studies. The developed excipient was also
      studied for acute toxicity in rats and found to be safe for oral use. RESULTS:
      Disintegration property of formed product was compared to known disintegrant (Ac
      Di-Sol) and it was found to give better results. The disintegration mechanism of
      developed disintegrant was postulated based on results obtained from various
      physical evaluations including: Study of effect of disintegrant concentration,
      fillers, and hardness, mode of incorporation and method of granulation on
      disintegration activity. CONCLUSIONS: By changing the condition parameters of
      well known crosslinking reaction of PVA, we obtained a crosslinked product which
      had excellent disintegration activity, good flow and optimal tableting
      properties.

PMID- 20816000
TI  - Improved sensitive high performance liquid chromatography assay for glucosamine
      in human and rat biological samples with fluorescence detection.
AB  - PURPOSE: An improved HPLC method with fluorescence detection was developed and
      validated for determination of glucosamine in human and rat biological samples.
      METHOD: Aliquot of 0.1 mL plasma was spiked with mannosamine HCl as the internal
      standard (IS); proteins were precipitated with acetonitrile; the clear layer was
      derivatized with 9-fluorenylmethyl chloroformate (8 mM/acetonitrile) in presence
      of borate 0.2 M buffer at 30 degrees C for 30 min. The excess derivatizing agent
      was removed with 1-aminoadamantane HCl (300 mM in acetonitrile-water 1:1).
      Chromatographic separation was achieved on a C18 (100 mm X 4.6 mm, id 3 microm)
      reversed phase column using 0.1% acetic acid/acetoniltrile gradient mobile phase
      at 1 mL/min flow rate. Glucosamine was determined in the plasma of a human and
      rats and also in rat urine. RESULTS: The analytes were detected at excitation and
      emission wavelengths of 263 and 315 nm, respectively. The assay was linear over
      the range of 0.05-20 microg/mL with a typical correlation coefficient of 0.999
      and intra-day and inter-day coefficient of variation of <15%. The lowest limit of
      quantification was set at 50 ng/mL. The recovery for glucosamine and mannosamine
      was 98 and 96%, respectively. CONCLUSION: We were able to improve glucosamine
      assay suitable to quantify glucosamine in both human and rat plasma and rat
      urine.

PMID- 20816001
TI  - Effects of stealth liposomal daunorubicin plus tamoxifen on the breast cancer and
      cancer stem cells.
AB  - PURPOSE: The cancer stem cells play an important role in the invasion, metastasis
      and relapse of cancers as they are resistant to regular chemotherapy. In the
      present study, stealth liposomal daunorubicin plus tamoxifen was developed for
      eradicating breast cancer cells together with cancer stem cells. METHODS:
      Inhibitory effects were performed on the bulk human breast cancer cells (MCF-7),
      the sorted MCF-7 cancer stem-like cells (side population, SP), and the sorted MCF
      7 cancer cells (NSP), respectively. Antitumor activity and TUNEL analysis were
      evaluated on the MCF-7 xenografts in nude mice. RESULTS: The encapsulation
      efficiencies of daunorubicin and tamoxifen were 95% and 90%, respectively. The
      mean particle size of the stealth liposomes was about 100 nm. Breast cancer stem
      cells were identified by the specific markers CD44+/CD24-, and isolated from bulk
      MCF-7 cells. When applying stealth liposomal daunorubicin plus tamoxifen, the
      inhibitory effects on both the breast cancer cells and the cancer stem cells were
      significantly increased in vitro, respectively. In the MCF-7 xenografts in mice,
      stealth liposomal daunorubicin plus tamoxifen showed the most favorable antitumor
      activity due to the passive targeting the tumor tissue and the synergistic
      effects in eliminating breast cancer cells and cancer stem cells. CONCLUSION:
      Stealth liposomal daunorubicin plus tamoxifen could have the potentials in
      eliminating both breast cancer cells and cancer stem cells.

PMID- 20816002
TI  - Reciprocal powered time model for release kinetic analysis of ibuprofen solid
      dispersions in oleaster powder, microcrystalline cellulose and crospovidone.
AB  - PURPOSE: A physically sound derivation for reciprocal power time (RPT) model for
      kinetic of drug release is given. In order to enhance ibuprofen dissolution, its
      solid dispersions (SDs) prepared by cogrinding technique using crospovidone (CP),
      microcrystalline cellulose (MC) and oleaster powder (OP) as a novel carrier and
      the model applied to the drug release data. METHODS: The drug cogrounds with the
      carriers were prepared and subjected to the dissolution studies. For elucidation
      of observed in vitro differences, FT-IR spectroscopy, X-ray diffraction patterns,
      DSC thermograms and laser particle size measurement were conducted. RESULTS: All
      drug release data fitted very well to newly derived RPT model. The efficiency of
      the carriers for dissolution enhancement was in the order of: CP>OP>MC. The
      corresponding release kinetic parameter derived from the model, t50% (time
      required for 50% dissolution) for the carrier to drug ratio 2:1 were 2.7, 10.2
      and 12.6 min, respectively. The efficiency of novel carrier, OP, was between CP
      and MC. FT-IR showed no interaction between the carriers and drug. The DSC
      thermograms and X-ray diffraction patterns revealed a slight reduced crystallinty
      in the SDs. Also grinding reduced mean particle size of drug from 150.7 to 44.4
      microm. CONCLUSIONS: An improved derivation for RPT model was provided which the
      parameter of the model, t50%, unlike to previous derivations was related to the
      most important property of the drug i.e. its solubility. The model described very
      well drug release kinetics from the solid dispersions. Cogrinding was an
      effective technique in enhancing dissolution rate of ibuprofen. Elaeagnus
      angostifolia fruit powder was suggested as a novel potential hydrophilic carrier
      in preparing solid dispersion of ibuprofen.

PMID- 20816003
TI  - Safety and efficacy of galactogogues: substances that induce, maintain and
      increase breast milk production.
AB  - Poor production of breast milk is the most frequent cause of breast lactation
      failure. Often, physician prescribe medications or other substances to solve this
      problem. The use of galactogogues should be limited to those situations in which
      reduced milk production from treatable causes has been excluded. One of the most
      frequent indication for the use of galactogogues is the diminution of milk
      production in mothers using indirect lactation, particularly in the case of
      preterm birth. The objective of this review is to analyze to the literature
      relating to the principal drugs used as galactogogues (metoclopramide,
      domperidone, chlorpromazine, sulpiride, oxytocin, growth hormone, thyrotrophin
      releasing hormone, medroxyprogesterone). Have been also analyzed galactogogues
      based on herbs and other natural substances (fenugreek, galega and milk thistle).
      We have evaluated their mechanism of action, transfer to maternal milk,
      effectiveness and potential side effects for mother and infant, suggested doses
      for galactogogic effect, and recommendation for breastfeeding.

PMID- 20816004
TI  - ASK1-P38 pathway is important for anoikis induced by microtubule-targeting aryl
      chloroethylureas.
AB  - PURPOSE: We investigated the involvement of MAPK signaling in the cell death
      mechanisms of classical microtubule interfering agents (MIA) and aryl-3-(2
      chloroethyl)ureas (CEU) acting as antimitotics, along with CEU that don't affect
      directly microtubules (non-MIA CEU). METHODS: To ascertain the activated
      signaling pathway profile of MIA and non-MIA CEU, Western blot,
      immunoprecipitation and transfection experiments were performed. RESULTS: Non-MIA
      CEU do not activate p38, as opposed to MIA, and the extent of ERK and JNK
      activation is lower than in response to MIA. The effect of MIA and non-MIA CEU on
      focal adhesion associated protein was also studied; MIA were shown to induce
      focal adhesion dismantlement associated with a sustained increase in paxillin
      phosphorylation and FAK cleavage, as opposed to non-MIA CEU. In addition, bcl-2
      phosphorylation and AKT cleavage, induced by all MIA tested, was not observed in
      response to non-MIA CEU further emphasizing the differential cell death
      mechanisms induced by MIA and non-MIA CEU. Pharmacologic and genetic approaches
      emphasize that the ASK1-p38 pathway activation contributes to the cytotoxic
      mechanism of MIA, in contrast to non-MIA CEU. ASK1-p38 is important for increased
      paxillin phosphorylation and FAK cleavage, suggesting that ASK-1-p38 is an
      upstream event of FA structure dismantlement induced by MIA. Moreover, the
      endogen inhibitor of ASK-1, thioredoxin, is released from ASK-1 in response to
      MIA as opposed to non-MIA CEU. CONCLUSION: Our study supports that ASK1-p38
      activation is an important signaling event, induced by MIA, which impairs focal
      adhesion structure and induces anchorage-dependent apoptosis or anoikis.

PMID- 20816005
TI  - The success rate of new drug development in clinical trials: Crohn's disease.
AB  - PURPOSE: To determine the risk of drug failure during clinical trial testing in
      Crohn's disease and determine what steps can be taken to improve outcomes. This
      is the first study to quantify such risk for a single disease. METHODS: Moderate
      to severe Crohn's disease was investigated by reviewing press releases from 1998
      to June 2008. Clinical trial failure causes were classified as commercial or
      clinical and compared with industry expectations. The risk of failure was also
      reviewed based on whether the compound was a small molecule drug or a biologic.
      Lastly, the role of the sponsor was examined, in determining whether the size of
      the firm involved in a drug program was predictive of the outcome of the study.
      RESULTS: More than a 120 press releases were reviewed yielding 37 drugs that met
      our search criteria. The cumulative success rate for drug development in Crohn's
      disease is 19%, from start to finish of clinical trial testing. New drug
      approvals are dominated by protein based therapeutics in this indication.
      Commercial and clinical failures both contributed substantially to the failure
      rates of new drugs. Phase I clinical testing appeared to offer little risk
      mitigation with pass rates at 95%. CONCLUSIONS: Funding intended to advance
      Crohn's disease must take into account the disease specific historical failure
      rate of drug development in forecasting any reasonable expectation of producing
      new therapies. As it currently stands, one in five drugs will be successfully
      approved that enter clinical trial testing in this indication. To manage this
      risk continued development of biologics over small molecule drugs may be
      warranted in this disease.

PMID- 20816006
TI  - Examining the role of metabolites in bioequivalence assessment.
AB  - PURPOSE: Investigate the role of metabolites in bioequivalence (BE) assessment.
      METHODS. Sets of ordinary differential equations are used to generate
      concentration - time data for both parent drug (P) and metabolite (M). The
      calculations include 24 subjects, two different formulations (Test, Reference),
      and a range of Test/Reference ratios for the fraction of dose absorbed and the
      rate of absorption. A summarized view of these results is made through the
      construction of three dimensional power curves. The criteria for the choice of
      the preferred analyte (P or M) are based on a sensitivity analysis of the
      bioequivalence measure (AUC, Cmax). The latter depends on the relative ability of
      P and M to reflect better the changes of the pharmacokinetic parameters and
      variability. RESULTS. The different sensitivity properties of P and M were
      reflected on the power curves. For AUC, the performance of metabolite is very
      similar to that of the parent drug for all scenarios and models examined. A more
      complex behaviour is evident for Cmax. In most of these cases, metabolite data
      show higher permissiveness in the percentages of acceptance. This attribute is
      more evident when P exhibits high elimination rate and/or the formation of M
      occurs rapidly. When the Test and Reference products have similar absorption
      profiles, metabolite data are preferable for the determination of bioequivalence.
      Parent drug has the advantage for detecting better the differences in the
      absorption rate of two drugs. The latter is counterbalanced by the increased
      sensitivity of P data to the variability of the data. CONCLUSIONS. Both parent
      drug and metabolite share the same ability to declare BE when AUC is used as a
      bioequivalence measure. In case of Cmax, metabolite data exhibit better
      performance when the T and R products are truly bioequivalent or the two
      formulations differ in their extent of absorption. Parent drug data are more
      sensitive to detect differences in the rate of absorption. However, in such
      cases, their information is much influenced by the increased variability.

PMID- 20816007
TI  - A new discriminative criterion for the development of Franz diffusion tests for
      transdermal pharmaceuticals.
AB  - PURPOSE: In vitro skin/membrane permeation profiling of topical pharmaceuticals
      is an important overall quality attribute in the evaluation of product
      consistency and it is also used for IVIVR (in vitro - in vivo relationship)
      purposes in product development and change control. Franz diffusion cell (FDC)
      experiments are emerging as a generally accepted methodology in this field, where
      the choice of operational conditions requires a data-supported justification
      towards the discriminating power of the test. A response function is therefore
      proposed to objectively quantify the discriminating power. METHODS: We evaluated
      the usefulness of the proposed response function by studying one of the
      operational conditions, i.e. the influence of receptor medium composition, on the
      FDC in vitro penetration behaviour of the model compound testosterone formulated
      in four different topical preparations, using both artificial membranes and
      dermatomed human skin. RESULTS: From the obtained cumulative amount of
      testosterone in the receptor fluid versus time curves, the permeability
      coefficient Kp of testosterone from each formulation was calculated. The
      evaluation of the discriminating power of the different media was performed using
      our new objective response function based upon an equal spread criterion of
      normalised Kp values. CONCLUSION: We demonstrated significant differences in
      discriminating power between the different media used, with the overall best
      results obtained with hydroxypropyl-beta-cyclodextrine (HPBCD) containing media.
      The proposed new criterion was found to be useful for the rational design of an
      in vitro diffusion test for transdermal pharmaceuticals.

PMID- 20816008
TI  - Evaluation of the protective effects of quercetin, rutin, naringenin, resveratrol
      and trolox against idarubicin-induced DNA damage.
AB  - PURPOSE: Idarubicin is a synthetic anthracycline anticancer drug widely used in
      the treatment of some hematological malignancies. The studies in our laboratory
      have clearly demonstrated that idarubicin can undergo reductive bioactivation by
      NADPH-cytochrome P450 reductase to free radicals with resulting formation of DNA
      strand breaks, which can potentially contribute to its genotoxic effects [Celik,
      H., Arinc, E., Bioreduction of idarubicin and formation of ROS responsible for
      DNA cleavage by NADPH-cytochrome P450 reductase and its potential role in the
      antitumor effect. J Pharm Pharm Sci, 11(4):68-82, 2008]. In the current study,
      our aim was to investigate the possible protective effects of several phenolic
      antioxidants, quercetin, rutin, naringenin, resveratrol and trolox, against the
      DNA-damaging effect of idarubicin originating from its P450 reductase-catalyzed
      bioactivation. METHODS: DNA damage was measured by detecting single-strand breaks
      in plasmid pBR322 DNA using a cell-free agarose gel method. RESULTS: Our results
      indicated that, among the compounds tested, quercetin was the most potent
      antioxidant in preventing DNA damage. Quercetin significantly decreased the
      extent of DNA strand breaks in a dose-dependent manner; 100 microM of quercetin
      almost completely inhibited the DNA strand breakage. Unlike quercetin, its
      glycosidated conjugate rutin, failed to provide any significant protection
      against idarubicin-induced DNA strand breaks except at the highest concentration
      tested (2 mM). The protective effects of other antioxidants were significantly
      less than that of quercetin even at high concentrations. Quercetin was found to
      be also an effective protector against DNA damage induced by mitomycin C.
      CONCLUSION: We conclude that quercetin, one of the most abundant flavonoids in
      the human diet, is highly effective in reducing the DNA damage caused by the
      antitumor agents, idarubicin and mitomycin C, following bioactivation by P450
      reductase.

PMID- 20816009
TI  - Characterization of selective TRPM8 ligands and their structure activity response
      (S.A.R) relationship.
AB  - PURPOSE: Transient receptor potential melastatin-8 (TRPM8) is an ion channel
      expressed extensively in sensory nerves, human prostate and overexpressed in a
      variety of cancers including prostate, breast, lung, colon and skin melanomas. It
      is activated by innoxious cooling and chemical stimuli. TRPM8 activation by
      cooling or chemical agonists is reported to induce profound analgesia in
      neuropathic pain conditions. Known TRPM8 agonists like menthol and icilin cross
      activate other thermo-TRP channels like TRPV3 and TRPA1 and mutually inhibit
      TRPM8. This limits the usefulness of menthol and icilin as TRPM8 ligands.
      Consequently, the identification of selective and potent ligands for TRPM8 is of
      high relevance both in basic research and for therapeutic applications. In the
      present investigation, a group of menthol derivates was characterized. These
      ligands are selective and potent agonists of TRPM8. Interestingly they do not
      activate other thermo-TRPs like TRPA1, TRPV1, TRPV2, TRPV3 and TRPV4. These ion
      channels are also nociceptors and target of many inflammatory mediators. METHODS:
      Investigations were performed in a recombinant system: Xenopus oocytes
      microinjected with cRNA of gene of interest were superfused with the test
      substances after initial responses of known standard agonists. Evoked currents
      were measured by two-electrode voltage clamp technique. RESULTS: The newly
      characterized ligands possess an up to six-fold higher potency (EC50 in low
      microM) and an up to two-fold increase in efficacy compared to the parent
      compound menthol. In addition, it is found that chemical derivatives of menthol
      like CPS-368, CPS-369, CPS-125, WS-5 and WS-12 are the most selective ligands for
      TRPM8. The enhanced activity and selectivity seems to be conferred by hexacyclic
      ring structure present in all ligands as substances like WS-23 which lack this
      functional group activate TRPM8 with much lower potency (EC50 in mM) and those
      with pentacyclcic ring structure (furanone compounds) are totally inactive.
      CONCLUSION: The new substances activate TRPM8 with a higher potency, efficacy and
      specificity than menthol and will thus be of importance for the development of
      pharmacological agents suitable for treatment and diagnosis of certain cancers
      and as analgesics. STATEMENT OF NOVELTY: The new compounds have an unmatched
      specificity for TRPM8 ion channels with additional display of high potency and
      efficacy. Thus these substances are better pharmacological tools for TRPM8
      characterization then known compounds and it is suggested that these menthol
      derivates may serve as model substances for the development of TRPM8 ligands.

PMID- 20816010
TI  - Relationship between LDL-C reduction after coronary revascularization and
      prevention of recurrence of cardiovascular events.
AB  - PURPOSE: The purpose of our study was to optimize lipid-lowering therapy in
      patients undergoing coronary revascularization and to determine whether the
      percentage change in low-density lipoprotein-cholesterol (LDL-C) level in the 3
      months after coronary revascularization could be used as a predictor of the time
      to recurrence of coronary artery disease (CAD). METHODS: Biochemical values of
      patients undergoing lipid-lowering therapy after receiving coronary
      revascularization at the Nippon Medical School Chiba Hokusoh Hospital, Japan,
      were retrospectively investigated. Recurrence of a cardiovascular event (CVE) was
      defined by death, myocardial infarction, or angina caused by coronary
      revascularization more than 3 months after the first event. RESULTS: Of 171
      patients under secondary preventive care who had at least one recurrence of a
      CVE, 75 showed evidence of objective stenotic lesions on coronary angiography.
      Among these 75 patients, exclusion of those in whom coronary revascularization
      had not been performed at disease onset, balloon dilatation had been used, serum
      lipid levels had not been measured, or coronary revascularization had been
      applied to restenosis left 44 patients suitable for inclusion in the study group.
      Although the mean value of high density lipoprotein-cholesterol did not change in
      the 3 months after coronary revascularization, that of (LDL-C) significantly
      decreased. A significant positive correlation was identified between % decrease
      in LDL-C and number of days to CVE recurrence. The average LDL-C value (102.8+/
      21.7 mg/dL) in the group of patients with no recurrence within 5 years was
      significantly lower than that (135.3+/-46.1 mg/dL) in the recurrence group (P =
      0.0088). The % of patients achieving the LDL-C target level (non-recurrence group
      vs. recurrence group: 50.0% vs. 16.7%; P = 0.032) and the % decrease in LDL-C
      (31.0%+/-12.6% vs. 9.6+/-21.0%, P = 0.0012) were significantly greater in the non
      recurrence group than in the recurrence group. CONCLUSIONS: From our present
      study, a decrease in LDL-C 3 months after revascularization surgery reduces the
      rate of CVE relapse. The % LDL-C decrease could serve as a useful predictor of
      CVE recurrence, in addition to LDL-C values and achievement of the LDL-C target
      level.

PMID- 20816011
TI  - Nasal delivery of recombinant human growth hormone: in vivo evaluation with
      Pheroid technology and N-trimethyl chitosan chloride.
AB  - PURPOSE: It was the aim of this study to investigate the possible enhancement of
      the absorption of recombinant human growth hormone (rhGH) in the nasal cavity, in
      the presence of a polymeric absorption enhancer, N-trimethyl chitosan chloride
      (TMC) and a fatty acid-based delivery system, Pheroid. METHODS: Two types of
      Pheroid formulations, Pheroid vesicles and Pheroid microsponges were
      characterized and evaluated with regard to particle size and morphology. In vivo
      bioavailability studies in rats were performed and the nasal bioavailability of
      Pheroid vesicles and Pheroid microsponges were compared relative to subcutaneous
      administration. The results were also compared with different N-trimethyl
      chitosan chloride (TMC) formulations, TMC H-L and TMC H-H, well studied
      absorption enhancers. RESULTS: Pheroid vesicles and Pheroid microsponges showed a
      size distribution of approxiamately 2-3 microm and 3-4 microm for Pheroid
      vesicles and Pheroid microsponges respectively. Using specific RIA, the relative
      bioavailability of rhGH after comparison with subcutaneous injection was
      determined to be 38.9, 128.5, 39.9, 136.3, and 8.3 % for Pheroid microsponges,
      Pheroid vesicles, TMC H-H, TMC H-L and control group (intranasal rhGH alone),
      respectively. All the enhancers showed significant absorption enhancement (P <
      0.05) with the highest effect observed with TMC H-L. CONCLUSIONS: All the
      enhancers may have promising potential as safe and effective nasal absorption
      enhancers of rhGH.

PMID- 20816012
TI  - Evaluation of protective effect of a water-in-oil microemulsion incorporating
      quercetin against UVB-induced damage in hairless mice skin.
AB  - PURPOSE: In the present study, histological aspects were considered in order to
      evaluate the in vivo photoprotective effect of a w/o microemulsion containing
      quercetin against UVB irradiation-induced dermal damages. The toxicity in cell
      culture and the potential skin irritation resulting from topical application of
      this formulation were also investigated. METHODS: Mouse dorsal surfaces were
      treated topically with 300 mg of the unloaded and quercetin-loaded (0.3%, w/w)
      microemulsions before and after exposure to UVB (2.87 J/cm2) irradiation. The
      untreated control groups irradiated and non-irradiated were also evaluated. UVB
      induced histopathological changes as well as the photoprotective effect of this
      formulation were evaluated considering the parameters of infiltration of
      inflammatory cells, epidermis thickening (basale and spinosum layers) and
      collagen and elastic fiber contents. The cytotoxicity of the reported formulation
      was evaluated in L929 mice fibroblasts by MTT assay and the skin irritation was
      investigated after topical application of both unloaded and quercetin-loaded
      microemulsions once a day for 15 days. RESULTS: The results demonstrated that the
      w/o microemulsion containing quercetin reduced the incidence of histological skin
      alterations, mainly the connective-tissue damage, induced by exposure to UVB
      irradiation, this allows the suggestion that protective effects of this
      formulation against UV-induced responses are not secondary to the interference of
      UV transmission (i.e., blocking the UVB radiation from being absorbed by the
      skin), as is usually done with UVB absorbers and sunscreens, but is instead due
      to different biological effects of this flavonoid. Furthermore, by evaluating the
      cytotoxic effect on L929 cells and histological aspects such as infiltration of
      inflammatory cells and epidermis thickness of hairless mice, the present study
      also demonstrated no toxicity of the proposed system. CONCLUSIONS: Therefore,
      based on these mouse models, a detailed characterization of the w/o microemulsion
      incorporating quercetin effects as a photochemoprotective agent on human skin is
      thus indicated.

PMID- 20816013
TI  - Influence of oleic acid on the rheology and in vitro release of lumiracoxib from
      poloxamer gels.
AB  - PURPOSE: Transdermal delivery of anti-inflammatory lumiracoxib (LM) could be an
      interesting strategy to avoid the side effects associated with systemic delivery,
      but it is ineffective due to the drug poor skin penetration. We have investigated
      the effects of oleic acid (OA), a lipid penetration enhancer, on the in vitro
      release of LM from poloxamer-based delivery systems (PBDS). The rheological
      behavior (shear rate dependent viscosity) and gelation temperature through
      measurements of optimal sol-gel transition temperatures (Tsol-gel) were also
      carried out in these systems. METHODS: In vitro release studies of LM from PBDS
      were performed using cellulose acetate as artificial membrane mounted in a
      diffusion system. The amount of LM released was divided by exposition area
      (microg/cm2) and these values were plotted as function of the time (h). The flux
      of the drug across the membrane (J) was calculated from the slope of the linear
      portion of the plot and expressed as microg/cm2. h -1. The determination of
      viscosity was carried out at different shear rates (gamma) between 0.1- 1000 S-1
      using a parallel plate rheometer. Oscillatory measurements using a cone-plate
      geometry rheometer surrounded by a double jacket with temperature varying 4-40
      degrees C, was used in order to determine Tsol-gel. RESULTS: Increase of both
      polymer and OA concentrations increases the viscosity of the gels and
      consequently reduces the in vitro LM release from the PBDS, mainly for gels
      containing OA at 10.0% compared to other concentrations of the penetration
      enhancer. Tsol-gel transition temperature was decreased by increasing viscosity;
      in some cases the formulation was already a gel at room temperature. Rheological
      studies showed a pseudoplastic behavior, which facilitates the flow and improves
      the spreading characteristics of the formulations. CONCLUSIONS: Taken together,
      the results showed that poloxamer gels are good potential delivery systems for
      LM, leading to a sustained release, and also have appropriate rheological
      characteristics. Novelty of the work: A transdermal delivery of non-steroidal
      antinflammatory drugs like lumiracoxib (LM) can be an interesting alternative to
      the oral route of this drug, since it was recently withdraw of the market due to
      the liver damage when systemically administered in tablets as dosage form. There
      are no transdermal formulations of LM and it could be an alternative to treat
      inflammation caused by arthritis or arthrosis. Then, an adequate delivery system
      to LM is necessary in order to release the drug properly from the PBDS as well as
      have good characteristics related to semi-solid preparations for transdermal
      application, which were evaluated through in vitro release studies and
      rheological behavior in this paper, respectively.

PMID- 20816014
TI  - Resveratrol protects against methotrexate-induced hepatic injury in rats.
AB  - PURPOSE: The aim of this study to investigate the possible protective effect of
      resveratrol on some liver and serum/plasma parameters in methotrexate induced
      toxicity in rats. Methotrexate is used widely to treat various neoplastic
      diseases such as acute lymphoblastic leukemia, lymphoma, solid cancers, and
      autoimmune diseases. We hypothesized that resveratrol has a potential to decrease
      the oxidant damage in MTX-induced hepatic injury. METHODS: Following a single
      dose of methotrexate (20 mg/kg, i.p.), either saline or resveratrol (10 mg/kg,
      orally) was administered for 5 days. After decapitation of the rats, trunk blood
      was obtained and the liver was removed to measure malondialdehyde and glutathione
      levels, myeloperoxidase and thromboplastic activities and collagen content.
      Aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase
      activity were measured in the serum samples, while TNF-alpha and total
      antioxidant capacity were assayed in plasma samples. RESULTS: Our results showed
      that MTX administration increased the hepatic malondialdehyde levels,
      myeloperoxidase and thromboplastic activities and collagen contents and decreased
      glutathione, while these alterations were reversed in resveratrol-treated group.
      Elevated aspartate aminotransferase and alanine aminotransferase activities and
      TNF-alpha level observed following MTX treatment was depressed with resveratrol.
      CONCLUSIONS: The present study showed that resveratrol protects against
      methotrexate-induced hepatic injury and may be of therapeutic potential in
      alleviating the systemic side effects of chemotherapeutics.

PMID- 20816015
TI  - Intravenous alpha-1 antitrypsin augmentation therapy: systematic review.
AB  - We reviewed the benefits and harms of augmentation therapy with alpha-1
      antitrypsin in patients with alpha-1 antitrypsin deficiency and lung disease. We
      searched for randomised trials comparing augmentation therapy with placebo or no
      treatment in PubMed and ClinicalTrials (7 January 2010). Two trials were included
      with a total of 140 patients. The trials ran for two to three years. Mortality
      data were not reported. There was no information on harms in the first trial; in
      the second trial, serious adverse events were reported in ten of 38 patients in
      the drug group and in 18 of 39 patients in the placebo group. Annual number of
      exacerbations and quality of life were reported in the second trial and were
      similar in the two groups. The meta-analyses showed that forced expiratory volume
      in one second deteriorated a little more in the drug group than in the placebo
      group (difference -20 ml per year; 95% confidence interval -41 to 1; p = 0.06).
      For carbon monoxide diffusion, the difference was -0.06 mmol/min./kPa per year
      (95% confidence interval -0.17 to 0.05; p = 0.31). Lung density measured by
      computed tomography deteriorated a little less in the drug group than in the
      placebo group (difference 1.14 g/l; 95% confidence interval 0.14 to 2.14; p =
      0.03) over the total course of the trials. Augmentation therapy with alpha-1
      antitrypsin cannot be recommended in view of the lack of evidence of clinical
      benefit and the cost of treatment.

PMID- 20816016
TI  - Fewer urological complications after laparoscopic inguinal hernia repair without
      indwelling catheter.
AB  - INTRODUCTION: The number of procedures involving transabdominal preperitoneal
      laparoscopic surgery for inguinal hernia (TAPP) has increased in Denmark.
      Optimized perioperative regimens are needed. MATERIAL AND METHODS: This
      retrospective, single-institution study included consecutive patients during an
      eight-year period from 1 January 2002 to 31 December 2007 (period I) and from 1
      January 2008 to 31 December 2009 (period II). In period II, perioperative
      indwelling catheter (Foley catheter) was not used routinely. Furthermore, the
      surgical technique was adjusted, a small team of dedicated TAPP surgeons was
      established, and two of the surgeons attended prearranged surgical training
      programmes. Additionally, period II patients were enrolled into structured
      patient protocols. The primary endpoint was complications within the first 30
      days after surgery, and we also registered the rate of reoperation due to
      recurrence. RESULTS: A total of 684 patients underwent TAPP surgery for 946
      inguinal hernias. From period I to II, the number of TAPP surgeons was reduced to
      a third and two surgeons received TAPP training. During period I, minor
      urological complications were observed in 5% (confidence interval (CI) 3.1-6.9%)
      compared with 1% in period II (0.0-2.5%). The overall morbidity rate was 13%.
      Serious complications were observed in 3% (CI 3.1-6.9%) of the cases in period I
      and in 2% (0.0-2.5%) of the cases in period II. For the entire eight-year study
      period, the cumulative rate of re-operation due to recurrence was 2%. CONCLUSION:
      TAPP without routine use of an indwelling catheter may reduce the risk of
      urological complications.

PMID- 20816017
TI  - Oral antibiotics for perforated appendicitis is not recommended.
AB  - In the majority of surgical departments in Denmark, the postoperative treatment
      for acute perforated appendicitis comprises three days of intravenous
      antibiotics. Recently, it has been proposed that such antibiotic regimen should
      be replaced by orally administered antibiotics. The aim of this paper was to give
      an overview of studies on acute perforated appendicitis with postoperative oral
      antibiotics. Five studies were found in a database search covering the 1966-2009
      period. There is no evidence to support a conversion of the postoperative
      antibiotic regimen from intravenous to oral administration in patients with acute
      perforated appendicitis.

PMID- 20816018
TI  - PET/CT may change diagnosis and treatment in cancer patients.
AB  - INTRODUCTION: The national focus on cancer has propelled the use of PET/CT for
      cancer imaging in Denmark. We believe that first-year experiences from a large
      PET centre may be of interest to new users. MATERIAL AND METHODS: Data from all
      scans made in the period from February 28 2006 to March 1 2007 with a single
      PET/CT scanner and 18F-fluoro-deoxyglucose (FDG) were collected prospectively
      along with information on action diagnosis, study purpose, etc. Referring
      departments indicated if PET/CT had changed or confirmed diagnosis, staging and
      treatment plan. RESULTS: A total of 970 scans were made in 826 patients, 14% had
      2-5 scans performed. Diagnostic CT was performed in 53%. In all, 792 referrals
      came from Odense University Hospital. Nearly 85% were from the specialities of
      oncology (31%), haematology (24%), surgery (14%), internal medicine (9%) and
      gynaecology (6%). PET/CT for primary diagnosis was mainly used in lung cancer and
      in cases with unknown primary tumour. In malignant lymphomas and colorectal
      cancer, the technique was mainly employed for response evaluation. Use of PET/CT
      for staging and recurrence was more evenly distributed across specialities.
      PET/CT changed the primary diagnosis in 16% and induced a change in staging and
      treatment plan in 28% to 32% of cases, respectively. CONCLUSION: FDG PET/CT was
      mainly used for diagnosis in lung cancer and in cases with an unknown primary
      tumour, and for response evaluation in lymphomas and colorectal cancer. PET/CT
      caused a change of staging and treatment plan in 25-33% of cases.

PMID- 20816019
TI  - Dendritic cell vaccination of patients with metastatic colorectal cancer.
AB  - Colorectal cancer is with more than 4000 new cases every year the third most
      common cancer in Denmark. Metastases are most often found in the liver, and 20
      25% of the patients have synchronous metastases to the liver at time of primary
      diagnosis. Other frequent sites for metastases are lungs and lymph nodes. Without
      treatment the median survival for patients with metastatic colorectal cancer is 7
      9 months. Patients receiving systemic or regional chemotherapy now have a median
      survival of approximately 20 months. Up to 40% of the patients undergoing
      intended curative surgery subsequently relapse with local or distant disease, and
      approximately 80% of the relapses appear within the first 3 years. If the cancer
      metastasises, and the chances of radical surgery are eliminated, the prognosis is
      poor. The aim of the present study was to evaluate the clinical and immunological
      effects of treating patients with disseminated colorectal cancer with a dendritic
      cell based cancer vaccine (MelCancerVac). The vaccine consisted of dendritic
      cells generated from autologous mononuclear cells pulsed with an allogeneic tumor
      cell lysate, selected for its high expression of cancer associated antigens. A
      clinical phase I study evaluating tolerability and toxicity of the treatment was
      established. Six patients with progressive disease were included and the analysis
      revealed that the treatment was well tolerated and not associated with toxicity.
      A subsequent clinical phase II study evaluating the activity of the treatment
      with CT-scan based measurements of tumors (RECIST), self reported quality of life
      (SF-36), and clinical evaluation was established. Out of twenty included patients
      with progressive disease, seventeen received intervention with the vaccine.
      Stable disease was achieved in four patients and two of these remained stable
      throughout the entire study period. Quality of life remained for most parameters
      included in the evaluation high and stable. The immunological consequences of the
      treatment were evaluated with plasma- and serum-levels of inflammatory and non
      inflammatory markers (the following 10 cytokines: GM-CSF, INF-gamma, IL-1beta, IL
      2, IL-4, IL-5, IL-6, IL-8, IL-10, and TNF-alpha, and in addition the inflammatory
      chemokines MIP-1beta, Eotaxin and IP-10) and biomarkers CEA and TIMP-1. These
      analyses showed that the vaccine induced increasing levels of Th1 cytokines such
      as GM-CSF, TNF-alpha, IFN-gamma, and IL-2 in patients achieving stable disease.
      Patients with progressive disease had increasing levels of CEA and TIMP-1, while
      patients achieving stable disease maintained relatively stable levels.
      Conclusively, treatment with this dendritic cell based cancer vaccine was non
      toxic and safe, clinical response in terms of stable disease was achieved in 24%
      of the patients, and the patients maintained a high quality of life during
      treatment. The immunological analyses indicated that the treatment resulted in
      favourable anticancer responses in the patients' immune system in terms of
      polarisation towards a Th1 dominated response potentially directed against tumor
      cells. Since no partial or complete responses were observed and since the number
      of patients was relatively low these results have to be interpreted with caution.
      Moreover, phase II study designs do not lead to final conclusions regarding
      clinical efficacy, which must be validated in larger prospective, randomised and
      controlled studies.

PMID- 20816020
TI  - Image fusion between ultrasonography and CT, MRI or PET/CT for image guidance and
      intervention - a theoretical and clinical study.
AB  - The aim of this thesis was to test the clinical application of image fusion
      involving US. The first study describes the accuracies of different methods of co
      registration in a phantom. The accuracy improved if co-registration was made from
      points or planes close to the area examined. The second study describes the
      accuracy of image-guided intervention on structures invisible to US but visible
      to CT or MRI. We measured a rate of success of biopsies in a phantom and found a
      rate of success, similar to that of conventional US-guided biopsy. In the third
      study, we found that the number of identifiable lesions by US increased by using
      the fusion-guided US, and the method was helpful as guidance for contrast
      enhanced US (CEUS) as it enabled us to focus on a specific area. In the fourth
      study we computed a program to fuse a 3D-US dataset with a PET/CT examination. We
      have presented some of the first results on accuracy of real-time image fusion
      involving US and of the application of the method to patients with liver lesions.

PMID- 20816021
TI  - Role of GLP-1 induced glucagon suppression in type 2 diabetes mellitus.
AB  - This project consisted of two parts: a biochemical part and clinical studies. The
      overall aim was to elucidate the defective regulation of glucagon secretion in
      type 2 diabetes (T2DM). The aim in the biochemical part was to develop a glucagon
      ELISA by using C- and N-terminal antibodies generated in the laboratory. Much
      effort was put into this attempt; however, we were unsuccessful and had to use an
      alternative method in our attempt to characterize the paradoxical diabetic
      glucagon response further. By using Sep-Pac and HPLC separation methods, plasma
      from patients with T2DM known to have a defective suppression of glucagon was
      analyzed using three antibodies and RIA. In this way the hyperglucagonaemia was
      found to consist mainly of authentic glucagon, rather than abnormally processed
      forms. The first clinical study included ten healthy controls matched to ten
      patients with T2DM. The aim was to investigate if GLP-1 induced glucagon
      inhibition was dose dependent and if suppression was equally potent in healthy
      controls and T2DM patients. Further, we investigated if the potency of the
      inhibition depended on the prevailing plasma glucose (PG) level. All participants
      were investigated with increasing doses of GLP-1 administered as iv-infusions and
      saline (control) during a glycaemic clamp at fasting plasma glucose (FPG) levels.
      Patients were investigated on a third occasion with GLP-1 infusions after an over
      night normalisation of PG using adjustable insulin infusions. From these
      experiments we were able to conclude that GLP-1-induced glucagon inhibition is
      dose-dependent, but surprisingly GLP-1 suppressed the alpha cell equally potently
      in patients and controls - and the suppression was independent of PG level.
      Therefore we concluded that the paradoxical glucagon response to orally ingested
      glucose is not caused by decreased potency of GLP-1 with respect to glucagon
      suppression. It may be due to the decreased secretion of this hormone reported in
      earlier studies. My second protocol aimed towards quantifying the glucose
      lowering effect of GLP-1-induced glucagon inhibition seen in patients with T2DM.
      The glucose-lowering effect of GLP-1 is due to both insulin stimulation leading
      to peripheral glucose disposal and glucagon inhibition resulting in decreased
      stimulation of hepatic glucose production. With a five-day protocol including
      both glycaemic and pancreatic clamps in ten patients with T2DM we were able to
      isolate the contribution of glucagon suppression to the increased glucose turn
      over seen during a GLP-1-glycaemic clamp, and interestingly it was equal to the
      known insulinotropic effect of GLP-1. Finally, we investigated patients with type
      1 diabetes (T1DM) and no residual beta cell function with oral glucose tolerance
      test (OGTT) and isoglycaemic intravenous glucose infusion (IIGI) in order to
      evaluate any differences in glucagon response to glucose +/- gastri-intestinal
      (GI)-stimulation. Here we found that despite a perfectly normal inhibition of
      glucagon during the IIGI in the T1DM, they had a defective glucagon suppression
      in response to orally ingested glucose and a paradoxical secretion of glucagon
      was seen as in T2DM. Hereby, we proved that glucagon suppression in response to
      hyperglycaemia does not entirely depend on intra-islet insulin effects as has
      been suggested. Therefore we conclude that GI-tract factors rather than
      intraislet dysregulation explain the paradoxical glucagon response in patients
      with diabetes.

PMID- 20816022
TI  - Genetics of dietary habits and obesity - a twin study.
AB  - Obesity has become a major health concern due to the increased risk of co
      morbidities, resulting in decreased quality of life, stigmatization, reduced
      working ability and early death. This causes a great challenge for the health
      care systems and results in increased direct costs related to treatment of
      obesity and co-morbidities, as well as increased indirect costs related to
      reduced function and withdrawal from the labour market. Both between and within
      societies, large variation in the prevalence of overweight and obesity exists.
      This variation is caused by differences in environmental exposures as well as
      genetic differences between individuals, resulting in differentiated
      susceptibility to environmental exposures. The evidence for genetic influence on
      anthropometry has previously been established and has been estimated to be 60-70%
      based on twin studies. These inter-individual differences can, however, not
      explain the increase in obesity prevalence during the past 70 years.
      Environmental factors must therefore play an important role in the obesity
      epidemic. Habitual diet is one of many environmental factors that potentially
      contribute to the inter-individual differences in body fat mass, but only limited
      evidence for associations between habitual dietary intake and anthropometry
      exists. Differences in habitual dietary intake are also partly determined by
      differences in genes influencing smell and taste preferences. But, so far, only
      few studies have investigated genetic influences on dietary intake in adults and
      the interplay between diet, genes and obesity. The focus of the thesis was to
      investigate the genetic and environmental influence on habitual diet and obesity
      as well as the association between habitual diet and anthropometry. The thesis is
      based on structural equation modelling of twin data from the Danish Twin Registry
      with special focus on the GEMINAKAR twin study that was performed in 1997-2000.
      In this study, anthropometric traits of the twin pairs were measured and habitual
      dietary intake was assessed through a food frequency questionnaire (FFQ). When
      studying body fat mass in population-based studies, the phenotype used is often
      the body mass index (BMI). This measure does, however, not specify whether excess
      body mass is due to excess fat mass and how the body fat is distributed. Studying
      the genetic and environmental correlations between the anthropometry measures in
      the GEMINAKAR sample showed that the genetic correlations between BMI, fat mass
      index (FMI) and waist circumference were high in men and that the genetic
      correlations between BMI, FMI, waist and hip circumference were high in women.
      For all anthropometric phenotypes, significant residual genetic influence
      existed. Based on information about habitual diet from the FFQ the genetic
      influence on total energy intake, macronutrient intake, as well as intake of
      energy from 20 food groups, was estimated. The proportion of variation in dietary
      intake explained by variation in genes differed between the dietary traits under
      study but for the majority of dietary variables the genetic influence was 20-50%.
      Accordingly, both diet and anthropometry is influenced by genetic variation. In
      order to control for potential confounding by genetic variation and shared
      environment on the association between habitual diet and body fat, the
      monozygotic twin pairs were selected and the associations between intrapair
      differences in dietary intake and intrapair differences in anthropometry were
      studied. For the majority of dietary traits, no associations or only weak
      associations were found. The study showed, however, consistent positive
      associations between intake of sugar-sweetened soft drink and BMI, FMI and waist
      circumference in men. Gene-environment interaction models showed that while high
      physical activity is associated with a down-regulation of genes predisposing to
      obesity, such effects were not found for protein intake. In conclusion, the
      studies included in this thesis contribute to the relatively limited existing
      literature, with insight into genetic determinants of habitual dietary intake,
      pleiotropic influences on anthropometry, and the interplay between diet, genes
      and obesity.

PMID- 20816023
TI  - Familial hemiplegic migraine.
AB  - Familial hemiplegic migraine (FHM) is a rare, dominantly inherited subtype of
      migraine with aura, where hemiplegia occurs during the aura phase. Mutation
      screening of families with FHM has revealed a range of different mutations. The
      mutated FHM genes code for ion transport proteins. Animal and cellular studies
      have associated the mutated FHM genes with disturbed ion homeostasis, altered
      cellular excitability and altered neurotransmitter release. Abnormal cortical
      excitability due to dysfunctional ion-channels might facilitate cortical
      spreading depression (CSD) and thereby migraine aura and migraine headache.
      Genotyped FHM patients offer us the chance to study the interplay between
      genotype and phenotype and may be regarded as a genetic migraine model. FHM
      studies might open for a better understanding of the molecular migraine
      pathology, and potentially help to unravel the pathogenesis of the more common
      migraine forms. We have therefore studied genotyped FHM patients to understand
      the effect of genotype on the response to migraine provoking substances. We show
      here that two known migraine triggers failed to induce more migraine aura or
      migraine headache in FHM-patients than in healthy controls, thus indicating that
      the FHM genotype does not confer hypersensitivity to these migraine triggers.
      This has implications for our understanding of the headache mechanisms and raises
      the question whether FHM share neurobiological background with the common types
      of migraine. The aims of the present thesis were to test the hypothesis that FHM
      mutations might be associated with hypersensitivity to known migraine triggers
      and, thereby, share pathophysiological pathways with the common types of
      migraine, but our results disprove this hypothesis. Thus, FHM seems very
      different from MO and MA, both genetically and pathophysiologically. The fact
      that FHM genes regulate ion homeostasis cannot be extrapolated to the common
      types of migraine.

PMID- 20816024
TI  - Health-related quality of life in early breast cancer.
AB  - The treatment of primary breast cancer usually consists of surgery often followed
      by adjuvant therapy (radiotherapy, chemotherapy, hormonal treatment, etc.) to
      reduce the risk of recurrence. The cancer diagnosis and the treatments may have
      significant impact on the patients' quality of life. This thesis deals with
      scientific aspects and clinical results of a study aimed at assessing the impact
      of breast cancer (and its treatment) on the patients' quality of life. Studies
      such as this assessing the problems and symptoms experienced by the patients are
      often referred to as health-related quality of life (HRQL) research. HRQL
      research deals with subjective experiences and raises challenging, scientific
      questions. Therefore, much attention was directed towards methodological issues
      in this clinically motivated project. The study was a prospective, longitudinal,
      questionnaire-based investigation of women with newly diagnosed breast cancer
      registered in the Danish Breast Cancer Co-operative Group's DBCG 89 Program. The
      patients were sub-divided into low-risk and high-risk patients. High-risk
      patients were offered randomisation in one of three randomised adjuvant therapy
      trials involving chemotherapy, ovarian ablation, and endocrine therapy. After a
      literature study and interviews with breast cancer patients, a questionnaire was
      composed that included two widely used standard questionnaires (EORTC QLQ-C30 and
      Hospital Anxiety and Depression (HAD) Scale) and a DBCG 89 Questionnaire
      developed for this study. A total of 1,898 eligible patients were invited by post
      to participate in the study involving six assessments over a 2-year period, and
      1,713 patients (90%) completed the first questionnaire. Furthermore, a
      questionnaire was sent to 872 women selected at random from the general
      population; 608 (70%) responded. The multi-item scales of the two standard
      questionnaires were analysed for so-called differential item functioning (DIF) in
      order to investigate whether the (summary) scale scores were adequate
      representations of the information obtained by the individual items. The DIF
      analyses identified a number of cases of DIF, which, among other things,
      contributed to detection of possible problems in the HAD Scale. It was concluded
      that DIF analyses are relevant when important analyses based on multi-item scales
      are made. A new way to evaluate the validity of questionnaires was developed. The
      results from questionnaires completed by patients were compared against results
      from open ended interviews with the same patients rated by observers. The idea
      was that if results were similar, the patients had then probably understood and
      completed the questionnaire items as intended. On the other hand, if results from
      self-assessment and interviews deviated, misunderstandings or other errors might
      have taken place, and the study would give insight into possible problems. Of 57
      breast cancer patients, 46 (81%) were successfully interviewed. In general, the
      agreement between patient-completed questionnaires and interviews was excellent,
      indicating very good validity. The median weighted kappa for the EORTC QLQ-C30
      was 0.85 (range 0.49-1.00); it was 0.79 (range 0.65-0.95) for the HAD Scale, and
      0.92 (range 0.51-1.00) for the DBCG 89 Questionnaire. However, the study
      identified a mechanism called selective reporting, which may affect results from
      most HRQL questionnaires: in order to provide correct and useful answers some
      patients do not report symptoms they believe are irrelevant to the study, e.g.,
      symptoms unrelated to cancer. This mechanism may lead to bias if results from
      patients are compared to results from populations reporting their symptoms more
      completely, e.g., general population samples. In contrast, this mechanism has
      little importance when results from different sub-groups of cancer patients are
      compared. In this study multiple variables were assessed at multiple points in
      time and we did not have a priori hypotheses for all these potential comparisons.
      Therefore, a staff survey involving experienced doctors and nurses was conducted
      in order to generate hypotheses that could be tested in the data from patients.
      We contacted 46 health care professionals and 36 (78%) responded. Overall, the
      staff survey did not prove very useful for the intended purpose. The main reason
      for this was probably that the health care professionals had limited insight into
      the patients' HRQL. A different approach to the problem of multiple hypothesis
      testing proved more useful. Hypotheses generated from the initial literature
      review were tested in the comparison of patients in chemotherapy against patients
      not in chemotherapy. The study of women selected at random from the general
      population showed that these women experienced a considerable degree of
      "morbidity" according to all three questionnaires. This shows that symptoms and
      problems reported by cancer patients may have causes other than cancer, and thus
      constitutes a good justification for the use of data from general population
      studies when interpreting data from cancer patients. The levels of anxiety and
      depression of low-risk breast cancer patients were found to be lower than those
      from the general population sample. After careful consideration we concluded that
      this finding was probably incorrect. The most important explanations were thought
      to be the wording of some HAD Scale items as well as two mechanisms that are not
      specific to the HAD Scale, the "selective reporting mechanism" found in the
      validation study, and the response-shift problem. These findings indicate - in
      contrast to the conclusion above - that the comparability of HRQL data from
      cancer patients and general population data must be questioned. However, as this
      is the first study to raise the problem, this issue needs further investigation.
      Based on the initial literature review and interviews we hypothesised that 30
      different HRQL issues would be impaired in patients undergoing CMF chemotherapy
      compared to patients not in chemotherapy; 23 of these hypotheses were confirmed.
      In addition, our study and other research suggest that other HRQL aspects may
      also be affected by chemotherapy. Thus, there is considerable evidence that
      patients in chemotherapy may experience effects on a wide spectrum of HRQL
      issues. Most other studies have assessed surprisingly few of the HRQL issues
      shown in our study to be impaired in patients receiving chemotherapy. Similarly,
      current review articles on HRQL effects of adjuvant chemotherapy mention only
      relatively few of these topics. Concerning HRQL after the treatment period, our
      main finding was that many symptoms and problems had declined or disappeared, but
      some persisted: anticipatory nausea, weight gain, endocrine effects (e.g., hot
      flushes/sweats, irregular bleedings/amenorrhea, vaginal dryness), disturbed
      sleep, and sexual dysfunction. These findings are in agreement with the
      literature. The staff study showed that experienced physicians and nurses did not
      expect many of the "scientifically well documented" consequences of chemotherapy.
      Taken together, our findings suggest that information to patients about
      chemotherapy should be more comprehensive than that which has been practised in
      most places. When compared against ovarian ablation, chemotherapy was associated
      with more impact on HRQL during the treatment period; only hot flushes/sweats
      were more pronounced in the ovarian ablation group. Thus, from an overall "HRQL
      perspective" ovarian ablation or suppression may be preferable. However, younger
      women may preserve their premenopausal status (including fertility) by having
      chemotherapy, and this may be an argument for chemotherapy or for temporary
      ovarian ablation via goserelin, rather than permanent ovarian ablation.
      Furthermore, while ovarian ablation/suppression may be preferable because of less
      impairment of HRQL, contemporary chemotherapeutic regimens may be more effective.
      These results indicate that for some patients, the HRQL data and results on
      treatment efficiency may be in conflict. There is no simple, universally correct
      solution to this dilemma. More research into patients' views and expectations to
      the health-care system in cases where medical decision-making involves complex
      trade-offs between treatment efficiency and HRQL issues is needed. Contrary to
      expectations, the analyses showed that fatigue and emotional function predicted
      the risk of recurrence and death independently of biological and clinical
      prognostic variables. In multivariate Cox regression analyses patients who were
      more fatigued or had poorer emotional function had a worse prognosis. These
      results are consistent with one small study, but are inconsistent with five
      similar studies in patients with primary breast cancer, which found no such
      associations. The reasons for these important differences are currently unknown.
      In conclusion, this study consisted of methodological and clinical investigations
      of HRQL in primary breast cancer patients. The initial questionnaire development
      resulted in a combination of questionnaires that was more comprehensive than in
      other similar studies. The results of the methodological studies generally
      supported the validity of the questionnaires but also gave important insights
      into potential scientific problems that are probably not restricted to the
      present study. These insights helped to prevent misinterpretations of the
      clinical data. The study provided the most detailed description of HRQL during
      and after breast cancer adjuvant chemotherapy to date, and compared results of
      chemotherapy against ovarian ablation. It also provided controversial results
      concerning the prognostic value of HRQL data. The combination of a large
      empirical study and several methodological sub-studies thus proved useful and
      gave new results.

PMID- 20816025
TI  - Pain inhibition is deficient in chronic widespread pain but normal in major
      depressive disorder.
AB  - BACKGROUND: Given the complex relationships between fibromyalgia and major
      depressive disorder (MDD), it has been suggested that fibromyalgia is a "masked"
      MDD. In experimental settings, fibromyalgia is associated with lowered pain
      thresholds (hyperalgesia) and deficient pain inhibition. Similarly, it has been
      recently proposed that the proneness of patients with MDD to develop chronic pain
      results from a deficit in pain inhibition. This cross-sectional study measured
      experimentally induced pain perception and inhibition in patients with MDD and
      patients with fibromyalgia. METHOD: Participants were 29 patients with
      fibromyalgia (American College of Rheumatology criteria), 26 patients with MDD
      (DSM-IV criteria), and 40 healthy controls who did not differ in age, sex, or the
      presence or absence of a menstrual cycle. Data were collected between June 2007
      and May 2008. Thermal stimuli were used to measure pain thresholds. Pain
      inhibition was elicited using a tonic thermal test (Peltier thermode)
      administered before and after activation of the diffuse noxious inhibitory
      controls (DNIC) by means of a cold pressor test. RESULTS: Thermal pain thresholds
      were higher in healthy controls compared to patients with MDD and patients with
      fibromyalgia. Pain ratings during the cold pressor test were lower in healthy
      controls and patients with MDD relative to patients with fibromyalgia. Finally,
      DNIC efficacy was stronger in healthy controls compared to patients with
      fibromyalgia, while no significant differences were found between healthy
      controls and patients with MDD. CONCLUSIONS: Our results suggest that (1)
      fibromyalgia and MDD are both associated with signs of hyperalgesia, (2)
      hyperalgesia is more pronounced in fibromyalgia, and (3) the deficit of pain
      inhibition is specific to fibromyalgia. As such, these results suggest that there
      is an overlap between fibromyalgia and MDD, but that fibromyalgia can be
      distinguished from MDD in terms of DNIC efficacy.

PMID- 20816026
TI  - A prospective study of hormone therapy and depression in community-dwelling
      elderly women: the Three City Study.
AB  - BACKGROUND: The potential benefits of hormone therapy (HT) in treating depressed
      postmenopausal women are controversial, and data on depression (re)emergence in
      the context of HT discontinuation are lacking. OBJECTIVE: To determine whether HT
      is associated with a modified risk of new-onset depressive symptoms in elderly
      women. METHOD: Current depressive symptomatology was evaluated in 4,069 community
      dwelling postmenopausal women aged 65 years and over who were randomly recruited
      from 3 French cities between 1999 and 2001. Depressive symptomatology was
      assessed using the Center for Epidemiologic Studies-Depression Scale at baseline
      and as part of the 2- and 4-year follow-up. RESULTS: Over the follow-up period,
      multivariate logistic regression analyses adjusted for sociodemographic
      variables, measures of physical health, and cognitive impairment failed to find a
      significant association between HT at baseline and the incidence of depressive
      symptoms. However further analysis indicated an increased risk of incident
      depressive symptoms for women using transdermal estradiol treatment combined with
      synthetic progestin specifically (odds ratio [OR] = 1.59; 95% CI, 1.01-2.50; P =
      .046). In addition, while women taking HT continuously over the 4-year follow-up
      did not show an increased risk of depressive symptoms, women who stopped their
      treatment early after study inclusion, had a significantly higher risk (OR =
      2.63; 95% CI, 1.52-4.55; P = .0005). CONCLUSIONS: Hormone therapy was not
      associated with a protective effect against the emergence of depressive symptoms
      in elderly postmenopausal women. However, discontinuing treatment could increase
      the risk of depressive symptoms. Data on the appropriate management of depression
      in the context of HT discontinuation among postmenopausal women require further
      investigation.

PMID- 20816027
TI  - Double-blind, placebo-controlled trial of topiramate augmentation in treatment
      resistant obsessive-compulsive disorder.
AB  - BACKGROUND: From 40% to 60% of obsessive-compulsive disorder (OCD) patients fail
      to tolerate or respond to selective serotonin reuptake inhibitors (SSRIs).
      Preclinical and neuroimaging studies have shown abnormally high glutamatergic
      concentrations in OCD patients and an association between decreased caudate
      glutamatergic concentrations and reduced OCD symptom severity after SSRI
      treatment. Topiramate inhibits glutamatergic conduction. METHOD: Thirty-six adult
      patients with DSM-IV-defined OCD were randomly assigned to topiramate (n = 18)
      and placebo (n = 18) groups in this 12-week, double-blind, placebo-controlled,
      parallel-groups trial. Subjects were taking the maximum SSRI dose they could
      tolerate for at least 12 weeks and their current dose for at least 6 weeks, which
      was maintained throughout the study. Primary outcome measures were changes in the
      Yale-Brown Obsessive Compulsive Scale (YBOCS) total score and compulsions and
      obsessions subscores. Patients were recruited and followed up between April 1,
      2003, and April 13, 2006. RESULTS: Using mixed regression models (time [weeks] *
      treatment), we found a significant treatment effect on the YBOCS compulsions (P =
      .014) subscale, but not the obsessions (P = .99) subscale or the total score (P =
      .11). Over the 12-week trial, the topiramate group (mean endpoint dose = 177.8 +/
      134.2 mg/d; range, 50-400 mg/d) showed an average linear decrease of 5.38 points
      on the compulsions subscale compared to 0.6 points in the placebo group. Thirteen
      topiramate and 14 placebo subjects completed the study. Topiramate was not well
      tolerated in this trial: 28% (5/18) of the subjects discontinued the drug for
      adverse effects, and 39% (7/18) had a dose reduction for this reason.
      CONCLUSIONS: The results of this first double-blind, placebo-controlled trial of
      topiramate augmentation for treatment-resistant OCD suggest that topiramate may
      be beneficial for compulsions, but not obsessions. Modifications in glutamatergic
      function may be responsible, at least in part, for the improved response in
      compulsions seen with topiramate. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00211744.

PMID- 20816028
TI  - Do efficacy and effectiveness samples differ in antidepressant treatment outcome?
      An analysis of eligibility criteria in randomized controlled trials.
AB  - BACKGROUND: Because of strict inclusion and exclusion criteria, results drawn
      from placebo-controlled randomized antidepressant efficacy trials may not be
      transferable to real-world patients. METHOD: This study was performed from March
      2000 to September 2005 as a prospective, multicenter follow-up. Patients were
      recruited from February 2000 to June 2005. All patients were hospitalized (N =
      1,014) and met DSM-IV criteria for major depressive episode. Assessments with the
      21-item Hamilton Depression Rating Scale were conducted biweekly until discharge.
      According to the most commonly applied exclusion criteria in randomized
      controlled antidepressant efficacy trials, patients were retrospectively divided
      into 2 groups: (1) patients not fulfilling exclusion criteria and therefore
      eligible for a randomized placebo-controlled trial, referred to as "efficacy
      sample," and (2) patients fulfilling at least 1 exclusion criterion, not being
      eligible for inclusion in an efficacy trial ("nonefficacy sample"). The efficacy
      sample was compared with the nonefficacy sample in terms of sociodemographic and
      clinical baseline variables and outcome measures, such as remission and response
      rates, 17-item Hamilton Depression Rating Scale mean scores, time to remission,
      and time to response. RESULTS: Significant differences were found, with the
      efficacy sample being older (P = .03) and being more often treated at a
      university hospital (P = .02). The efficacy sample demonstrated superior outcome
      only in significantly higher mean Global Assessment of Functioning scores at
      discharge (P = .03). There were no differences regarding remission (P = .68) and
      response (P = .06) rates, length of hospital stay (P = .49), 17-item Hamilton
      Depression Rating Scale total score at discharge (P = .13), or time to response
      (P = .39) or remission (P = .16). CONCLUSIONS: Both groups differed significantly
      in several baseline measures and final Global Assessment of Functioning scores
      but not in any other outcome measure. Challenging current beliefs, our findings
      show that results from efficacy antidepressant trials might be more generalizable
      than previously thought.

PMID- 20816029
TI  - Detection of subclinical depression in bipolar disorder: a cross-sectional, 4
      month prospective follow-up study at community mental health services (SIN
      DEPRES).
AB  - OBJECTIVE: The aim of this study was to assess the prevalence and the impact of
      depressive symptoms on the functional outcome of bipolar disorder outpatients in
      remission. METHOD: A cross-sectional, prospective 16-week study of a cohort of
      739 euthymic bipolar disorder patients (DSM-IV-TR criteria) recruited by 94
      investigators was conducted. Clinical stability was assessed at baseline and at
      week 16 with the modified Clinical Global Impressions Scale-Bipolar Version, and
      depressive symptoms were assessed at baseline with the 17-item Hamilton
      Depression Rating Scale (HDRS-17 [primary endpoint measure]), the Montgomery
      Asberg Depression Rating Scale (MADRS), and the self-applied Center for
      Epidemiologic Studies-Depression Scale (CES-D). Functional status was evaluated
      with the Social and Occupational Functioning Assessment Scale (SOFAS) and Social
      Adaptation Self-evaluation Scale (SASS). The study was conducted from April 2006
      to March 2007. RESULTS: Subclinical depressive symptoms (SDS) were detected on
      the HDRS-17 in 16.9% of the sample. In symptom-free patients, the incidence of
      new SDS after 16 weeks was 20% (MADRS score > 7). At baseline, SDS patients
      compared to non-SDS patients presented with poorer social-occupational
      performance (SOFAS score mean difference, -11.9; 95% CI, -14.2 to -9.6) and
      poorer social adjustment (SASS score mean difference, -5.6; 95% CI, -7.1 to 
      4.1). Depressive symptoms were inversely related to functional status and social
      adjustment: MADRS-SOFAS correlation coefficients, r = -0.54 (P < .0001), and
      MADRS-SASS correlation coefficients, r = -0.42 (P < .0001). The self-applied
      survey identified additional cases with depressive symptoms, showing an SDS total
      prevalence of 44.9%. CONCLUSIONS: Depressive symptoms in apparently remitted
      bipolar disorder outpatients are not rare and result in a decline in occupational
      outcome and social maladjustment.

PMID- 20816030
TI  - Representativeness of participants in a clinical trial for attention
      deficit/hyperactivity disorder? Comparison with adults from a large observational
      study.
AB  - BACKGROUND: Clinical trials have demonstrated that pharmacotherapies can safely
      treat attention-deficit/hyperactivity disorder (ADHD) in adulthood. Eligibility
      criteria in these trials may significantly limit their external validity by
      excluding a significant portion of adults with ADHD in the general population. In
      particular, exclusion criteria may frequently exclude individuals with comorbid
      mental health conditions, which are common in the adult ADHD population. METHOD:
      We addressed the representativeness of clinical trials by comparing 146 adult
      clinical trial participants with DSM-IV ADHD and a community sample composed of
      124 adults with DSM-IV ADHD and 123 non-ADHD controls. Subjects were compared on
      socioeconomic status, Hollingshead occupational code, cognitive measures,
      lifetime psychopathology, and Global Assessment of Functioning (GAF) scale
      ratings. RESULTS: Adults with ADHD in the community sample had higher rates of
      lifetime psychiatric comorbidity, lower GAF scores, and lower occupational codes
      than those in the clinical trial. The clinical trial eligibility criteria would
      have excluded 61% of community sample adults with ADHD. This excluded portion of
      the community sample had higher rates of lifetime psychiatric comorbidity and
      lower GAF scores than clinical trial participants. CONCLUSIONS: Adults with ADHD
      participating in the clinical trial had less evidence of functional impairment
      and endorsed less psychiatric comorbidity than the majority of community sample
      subjects with ADHD. This suggests that findings from clinical trials may have
      limited external validity for adults with ADHD in the general population,
      particularly for those adults with ADHD with the greatest burden of comorbid
      psychopathology.

PMID- 20816031
TI  - Treatment outcomes of patients with tardive dyskinesia and chronic schizophrenia.
AB  - OBJECTIVE: We compared the response to antipsychotic treatment between patients
      with and without tardive dyskinesia (TD) and examined the course of TD. METHOD:
      This analysis compared 200 patients with DSM-IV-defined schizophrenia and TD and
      997 patients without TD, all of whom were randomly assigned to receive one of 4
      second-generation antipsychotics. The primary clinical outcome measure was time
      to all-cause treatment discontinuation, and the primary measure for evaluating
      the course of TD was change from baseline in Abnormal Involuntary Movement Scale
      (AIMS) score. Kaplan-Meier survival analysis and Cox proportional hazards
      regression models were used to compare treatment discontinuation between groups.
      Changes in Positive and Negative Syndrome Scale (PANSS) and neurocognitive scores
      were compared using mixed models and analysis of variance. Treatment differences
      between drugs in AIMS scores and all-cause discontinuation were examined for
      those with TD at baseline. Percentages of patients meeting criteria for TD
      postbaseline or showing changes in AIMS scores were evaluated with chi(2) tests.
      Data were collected from January 2001 to December 2004. RESULTS: Time to
      treatment discontinuation for any cause was not significantly different between
      the TD and non-TD groups (chi(2)(1) = 0.11, P = .743). Changes in PANSS scores
      were not significantly different (F(1,974) = 0.82, P = .366), but patients with
      TD showed less improvement in neurocognitive scores (F(1,359) = 6.53, P = .011).
      Among patients with TD, there were no significant differences between drugs in
      the decline in AIMS scores (F(3,151) = 0.32, P = .811); 55% met criteria for TD
      at 2 consecutive visits postbaseline, 76% met criteria for TD at some or all
      postbaseline visits, 24% did not meet criteria for TD at any subsequent visit,
      32% showed a >= 50% decrease in AIMS score, and 7% showed a >= 50% increase in
      AIMS score. CONCLUSIONS: Schizophrenia patients with and without TD were similar
      in time to discontinuation of treatment for any cause and improvement in
      psychopathology, but differed in neurocognitive response. There were no
      significant differences between treatments in the course of TD, with most
      patients showing either persistence of or fluctuation in observable symptoms.
      TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00014001.

PMID- 20816032
TI  - Suicidality as rare adverse event of antidepressant medication: report from the
      AMSP multicenter drug safety surveillance project.
AB  - OBJECTIVE: Since the advent of antidepressant drug treatment, the question of
      whether these substances induce suicidal ideation and behavior has not been
      satisfactorily answered. The aim of this study is to contribute to this ongoing
      discussion by taking a heuristic case-based approach to the question. METHOD: A
      large data set from a European drug surveillance program (Arzneimittelsicherheit
      in der Psychiatrie; AMSP) performed in 85 psychiatric hospitals from 1993 until
      2008 was analyzed. A series of single cases were carefully assessed. The observed
      frequencies of adverse drug reactions (ADRs) in this sample were related to the
      total AMSP population, who used the imputed medication. RESULTS: A total of
      142,090 adult patients taking antidepressant medication were observed. Thirty
      three incidents of suicidality (12 cases of suicidal ideation, 18 attempts, and 3
      completed suicides) were documented. Fourteen cases were assumed to be probably,
      and 19 to be possibly, related to the drug. Twenty-three cases judged as suicidal
      ADRs were associated with restlessness, 10 with ego-dystonia, 9 with
      impulsiveness, and 3 with psychosis. A higher incidence of suicidal ADRs was
      observed for selective serotonin reuptake inhibitors (0.034%; 95% CI, 0.020
      0.054) and serotonin-norepinephrine reuptake inhibitors (0.034%; 95% CI, 0.015
      0.068) compared to noradrenergic and specific serotonergic antidepressants
      (0.009%; 95% CI, 0.002-0.027) and tricyclic antidepressants (0.002%; 95% CI,
      0.000-0.014). CONCLUSION: Despite the methodological limitations of this study,
      the large AMSP data set supports the assumption that antidepressant drugs rarely
      trigger suicidality.

PMID- 20816033
TI  - Pharmacotherapy for the treatment of acute bipolar II depression: current
      evidence.
AB  - OBJECTIVE: Bipolar II disorder is a common, recurrent, and disabling psychiatric
      illness, and yet little is known about how best to treat it. The pressing
      clinical need for evidence-based approaches to the treatment of bipolar II
      disorder, coupled with recent publication of pertinent studies, calls for an
      updated review of this literature. This review focuses on a critical examination
      of the evidence supporting the efficacy of treatments for acute depressive
      episodes in bipolar II disorder. DATA SOURCES: A MEDLINE (via Ovid) search of
      journals, covering the period from January 1950 to January 2009, was performed to
      identify relevant studies. Keywords used were bipolar II disorder, bipolar
      disorder, bipolar depression, and pharmacotherapy. Studies were further limited
      to those that were in adult samples, published in peer-reviewed journals, and
      written in English. STUDY SELECTION: We examined all randomized trials evaluating
      the use of pharmacotherapy in the treatment of acute bipolar II depression.
      Studies with mixed samples of bipolar I and II or bipolar II and unipolar
      depression were examined as well. Twenty-one randomized trials were identified
      and reviewed. DATA EXTRACTION: Therapeutic agents were rated according to the
      quality of evidence supporting their efficacy as treatments for bipolar II
      depression. DATA SYNTHESIS: Ninety percent of relevant trials were published
      after 2005. Quetiapine was judged as having compelling evidence supporting its
      efficacy. Lithium, antidepressants, and pramipexole were judged as having
      preliminary support for efficacy. Lamotrigine was considered to have mixed
      support. CONCLUSIONS: Although progress has been made, further research on
      bipolar II depression is warranted.

PMID- 20816035
TI  - White matter hyperintensities, medial temporal lobe atrophy, cortical atrophy,
      and response to electroconvulsive therapy in severely depressed elderly patients.
AB  - OBJECTIVE: Electroconvulsive therapy (ECT) is a valuable treatment option in
      severely depressed elderly patients. Structural abnormalities in the brain, such
      as white matter hyperintensities, medial temporal lobe atrophy (MTA), or global
      cortical atrophy, may influence therapeutic response. The respective value of
      these factors in response prediction is unclear. METHOD: In a naturalistic
      clinical cohort of 81 elderly patients diagnosed with DSM-IV major depressive
      disorder, magnetic resonance imaging (MRI) was recorded and rated before ECT
      treatment. The study was conducted at the clinic for Geriatric Psychiatry of the
      VU University Medical Center/Stichting Buitenamstel Geestgronden, Amsterdam, The
      Netherlands, over a 5-year period (2001-2006). Severity of depressive symptoms
      was measured by using the Montgomery-Asberg Depression Rating Scale (MADRS).
      Response to ECT was defined as a decrease of at least 50 percent on the MADRS,
      and remission was defined as a score below 10 points on the MADRS. RESULTS:
      Patients with moderate or severe MTA had a lower mean percentage decrease in
      MADRS scores after ECT (37.9% in those with MTA, compared to 66.2% in those
      without MTA, P = .008). Patients without MTA had a 3 times greater chance of
      remitting from their depression compared to patients with moderate or severe MTA,
      ie, the hazard ratio for remission was 3.22 (95% CI, 1.30 to 7.69, P = .01). In
      contrast, no differences in change in MADRS scores were found for white matter
      hyperintensities or global cortical atrophy. CONCLUSIONS: Medial temporal lobe
      atrophy--not white matter hyperintensities or global cortical atrophy-
      contributes to poor response to ECT in severely depressed elderly patients. These
      findings suggest that assessment of MTA in severely depressed elderly patients
      may be useful in the prediction of potential ECT response.

PMID- 20816034
TI  - Twelve-month prevalence of and risk factors for suicide attempts in the World
      Health Organization World Mental Health Surveys.
AB  - OBJECTIVE: Although suicide is a leading cause of death worldwide, clinicians and
      researchers lack a data-driven method to assess the risk of suicide attempts.
      This study reports the results of an analysis of a large cross-national
      epidemiologic survey database that estimates the 12-month prevalence of suicidal
      behaviors, identifies risk factors for suicide attempts, and combines these
      factors to create a risk index for 12-month suicide attempts separately for
      developed and developing countries. METHOD: Data come from the World Health
      Organization (WHO) World Mental Health (WMH) Surveys (conducted 2001-2007), in
      which 108,705 adults from 21 countries were interviewed using the WHO Composite
      International Diagnostic Interview. The survey assessed suicidal behaviors and
      potential risk factors across multiple domains, including sociodemographic
      characteristics, parent psychopathology, childhood adversities, DSM-IV disorders,
      and history of suicidal behavior. RESULTS: Twelve-month prevalence estimates of
      suicide ideation, plans, and attempts are 2.0%, 0.6%, and 0.3%, respectively, for
      developed countries and 2.1%, 0.7%, and 0.4%, respectively, for developing
      countries. Risk factors for suicidal behaviors in both developed and developing
      countries include female sex, younger age, lower education and income, unmarried
      status, unemployment, parent psychopathology, childhood adversities, and presence
      of diverse 12-month DSM-IV mental disorders. Combining risk factors from multiple
      domains produced risk indices that accurately predicted 12-month suicide attempts
      in both developed and developing countries (area under the receiver operating
      characteristic curve = 0.74-0.80). CONCLUSIONS: Suicidal behaviors occur at
      similar rates in both developed and developing countries. Risk indices assessing
      multiple domains can predict suicide attempts with fairly good accuracy and may
      be useful in aiding clinicians in the prediction of these behaviors.

PMID- 20816036
TI  - Health-related quality of life across the anxiety disorders: results from the
      national epidemiologic survey on alcohol and related conditions (NESARC).
AB  - OBJECTIVE: Although clinical studies have documented that specific anxiety
      disorders are associated with impaired psychosocial functioning, little is known
      regarding their comparative effects on health-related quality of life within a
      general population. The current analysis compares health-related quality of life
      in a US community-dwelling sample of adults with DSM-IV social anxiety disorder,
      generalized anxiety disorders (GAD), panic disorder, and specific phobia. METHOD:
      A face-to-face survey of a US nationally representative sample of over 43,000
      adults aged 18 years and older residing in households and group quarters was
      conducted. Prevalence of DSM-IV anxiety disorders and relative associations with
      health-related quality of life indicators were examined. The survey was conducted
      from 2001 to 2002. RESULTS: Roughly 9.8% of respondents met diagnostic criteria
      for at least 1 of 4 twelve-month DSM-IV anxiety disorders which, relative to the
      non-anxiety-disordered general population, were each associated with lower
      personal income, increased rates of 12-month physical conditions, and greater
      numbers of Axis I and Axis II DSM-IV psychiatric conditions. After adjusting for
      sociodemographic and clinical correlates, including other anxiety disorders, GAD
      was associated with significant decrements in the SF-12 mental component summary
      score. In similar models, GAD and, to a lesser extent, panic disorder were
      significantly associated with impairment in social functioning, role emotional,
      and mental health SF subscales. CONCLUSIONS: GAD, followed by panic disorder,
      appears to exact significant and independent tolls on health-related quality of
      life. Results underscore the importance of prompt and accurate clinical
      identification and improving access to effective interventions for these
      disorders.

PMID- 20816037
TI  - Orlistat in clozapine- or olanzapine-treated patients with overweight or obesity:
      a 16-week open-label extension phase and both phases of a randomized controlled
      trial.
AB  - OBJECTIVE: To explore long-term effects of orlistat in adult clozapine- or
      olanzapine-treated patients with DSM-IV-diagnosed schizophrenia and overweight or
      obesity who tolerate orlistat. METHOD: Orlistat or placebo was added to clozapine
      or olanzapine in stable doses in a 16-week randomized controlled trial. Open
      label orlistat was added to the antipsychotics during a 16-week extension phase
      for those completing the double-blind phase. No low-calorie diet or participation
      in behavioral programs was required. Body weight (primary outcome) and some
      metabolic parameters were measured prospectively. Analyses were performed for
      those completing both phases (ie, population differing from that reported
      earlier). The study was conducted from 2004 through 2005. RESULTS: During the
      open-label phase, the 44 patients experienced mean +/- SD body weight loss of 
      1.29 +/- 3.04 kg, P = .007. During both phases, men (but not women) showed a
      weight loss of -2.39 +/- 5.45 kg, P = .023. Some subgroups showed desirable
      changes in several metabolic parameters. Prolonged (32 weeks) orlistat treatment
      yielded no additional benefits as compared to short (16 weeks) treatment.
      CONCLUSIONS: In clozapine- or olanzapine-treated overweight or obese patients
      able to take orlistat on a long-term basis, the drug, with no concomitant
      hypocaloric diet or behavioral interventions, caused moderate weight loss only in
      men. However, some metabolic benefits may be achieved independently of weight
      changes. In patients who do not respond to orlistat within the first 16 weeks,
      continuation treatment may provide no additional benefits. TRIAL REGISTRATION:
      controlled-trials.com Identifier: ISRCTN65731856.

PMID- 20816039
TI  - Analysis of suicidality in pooled data from 2 double-blind, placebo-controlled
      aripiprazole adjunctive therapy trials in major depressive disorder.
AB  - OBJECTIVE: To assess the impact of adjunctive aripiprazole versus adjunctive
      placebo treatment on suicidality in patients with major depressive disorder.
      METHOD: Data were pooled from 2 identical aripiprazole augmentation studies.
      Patients with DSM-IV-TR-diagnosed major depressive disorder with an inadequate
      response to 8 weeks of prospective antidepressant treatment were randomly
      assigned to adjunctive placebo or adjunctive aripiprazole (2-20 mg/d) treatment
      for 6 weeks. Adverse events related to suicidality were identified in the adverse
      event database using the Medical Dictionary for Regulatory Activities-preferred
      term. Treatment-emergent suicidal ideation was defined using item 10
      (suicidality) of the Montgomery-Asberg Depression Rating Scale (MADRS) and item
      18 (suicidality) of the Inventory of Depressive Symptomatology (IDS). RESULTS: In
      total, 737 patients were included in the safety database (aripiprazole n = 371;
      placebo n = 366). No suicides were reported. There were no treatment-emergent,
      suicide-related adverse events in the aripiprazole group; 2 patients in the
      placebo group had >= 1 adverse event related to suicide (both suicidal ideation).
      More placebo than aripiprazole patients > 25 years old experienced a 2-point (P <
      .01) or 1-point (P < .05) worsening of MADRS item 10 scores. For this age group,
      2-point improvement in MADRS item 10 scores and 1-point improvement of IDS item
      18 scores were significantly more common in aripiprazole patients than placebo
      patients (both P < .05). CONCLUSIONS: This post hoc analysis demonstrated that
      adjunctive aripiprazole treatment in patients with depression with a history of
      an inadequate response to antidepressant medication is associated with a
      decreased rate of suicidality in a group of subjects not at significant risk.
      Prospective trials directly assessing suicidality are needed to further
      understand the benefits of an adjunctive antipsychotic in an at-risk population.
      TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT00095823 and NCT00095758.

PMID- 20816038
TI  - Lifetime prevalence of mood and anxiety disorders in fragile X premutation
      carriers.
AB  - OBJECTIVE: The authors studied the lifetime prevalence of DSM-IV-TR psychiatric
      disorders in a population of adults with the fragile X premutation. METHOD: The
      Structured Clinical Interview for DSM-IV was conducted, from 2007-2008, in 85
      individuals with the fragile X premutation, 47 with the fragile X-associated
      tremor/ataxia syndrome (FXTAS; 33 male, 14 female; mean age = 66 years) and 38
      without FXTAS (16 male, 22 female; mean age = 52 years). Lifetime prevalence for
      mood and anxiety disorders among carriers with and without FXTAS was compared to
      available age-specific population estimates from the National Comorbidity Survey
      Replication (NCS-R). RESULTS: Among participants with FXTAS, 30 (65%) met
      lifetime DSM-IV-TR criteria for a mood disorder; 24 (52%) met lifetime DSM-IV-TR
      criteria for an anxiety disorder. Among the non-FXTAS participants, there were 15
      instances of lifetime mood disorder (42%) and 18 of lifetime anxiety disorder
      (47%). When compared to age-specific NCS-R data, the lifetime prevalences of any
      mood disorder (P < .0001), major depressive disorder (P < .0001), any anxiety
      disorder (P < .0001), panic disorder (P = .006), specific phobia (P = .0003), and
      posttraumatic stress disorder (P = .004) were significantly higher in
      participants with FXTAS. The lifetime rates of social phobia in individuals with
      the premutation without FXTAS were significantly higher than NCS-R data (P =
      .001). CONCLUSIONS: This sample of carriers of the fragile X premutation had a
      notably high lifetime risk of mood and anxiety disorders. Mood and anxiety
      disorders may be part of the clinical phenotype of the fragile X premutation
      conditions, especially in carriers with FXTAS. Clinicians encountering these
      patients are advised to consider FXTAS as a neuropsychiatric syndrome as well as
      a neurologic disorder.

PMID- 20816040
TI  - Enhanced prefrontal function with pharmacotherapy on a response inhibition task
      in adolescent bipolar disorder.
AB  - OBJECTIVE: The aim of the current study is to determine whether pharmacotherapy
      normalizes cognitive circuitry function supporting voluntary behavioral
      inhibition in adolescent bipolar disorder. METHOD: Healthy controls and
      unmedicated patients with DSM-IV adolescent bipolar disorder in manic, mixed, or
      hypomanic episodes were matched on demographics and IQ (n = 13 per group; mean
      age = 14.4 +/- 2.4 years). Functional magnetic resonance imaging studies were
      performed at baseline and after 14 weeks, during which time patients with
      adolescent bipolar disorder were treated initially with second-generation
      antipsychotics (SGAs) followed by lamotrigine monotherapy. The primary outcome
      measure was a Response Inhibition Task, which involved a planned motor response,
      already "on the way" to execution, that had to be voluntarily inhibited by the
      subjects in the trials in which a stop signal was presented. There were 6 blocks,
      each with a predominant rate of either "go" or "stop" trials. The study was
      conducted from June 2006 through July 2009. RESULTS: All patients showed
      significant improvement (P < .001) in both the manic and depressive symptoms from
      baseline. Behavioral data showed that accuracy improved over 14 weeks in patients
      and healthy controls. Significant time by group interaction effects for the
      difference between stop versus go blocks showed greater increases of activation
      in prefrontal (left inferior and middle frontal gyri and medial frontal gyrus
      bilaterally) and temporal (left superior temporal gyrus and right middle temporal
      gyrus) regions and greater decreases in activation in right putamen and bilateral
      thalamus at follow-up in the adolescent bipolar disorder group than in healthy
      controls. Increased ventrolateral prefrontal cortex function was related to
      clinical treatment response. CONCLUSIONS: Treatment with SGAs followed by
      lamotrigine monotherapy enhanced prefrontal and temporal lobe activity during a
      Response Inhibition Task demonstrating the reversal of disorder-relevant neural
      circuitry dysfunction in patients with adolescent bipolar disorder. Patient
      performance was not slowed down with this treatment regimen. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00176228.

PMID- 20816041
TI  - Acute efficacy of divalproex sodium versus placebo in mood stabilizer-naive
      bipolar I or II depression: a double-blind, randomized, placebo-controlled trial.
AB  - OBJECTIVE: To conduct an exploratory evaluation of the acute efficacy of extended
      release divalproex sodium compared to placebo in patients with bipolar I or II
      depression. METHOD: Outpatients aged 18-70 years with mood stabilizer-naive
      bipolar I or II disorder experiencing a major depressive episode (DSM-IV) were
      randomly assigned to 6 weeks of divalproex sodium monotherapy or placebo. The
      primary outcome measure was mean change from baseline to week 6 on the Montgomery
      Asberg Depression Rating Scale (MADRS) total score. Secondary outcomes included
      rates of response and remission, changes in the Clinical Global Impressions
      Bipolar (CGI-BP) Severity of Illness scores, and changes in anxiety symptoms as
      measured by the Hamilton Anxiety Rating Scale. The study was conducted between
      2003 and 2007. RESULTS: Fifty-four subjects with bipolar I (n = 20) or bipolar II
      (n = 34) disorder were randomly assigned to divalproex or placebo; 67% (36 of 54)
      met DSM-IV criteria for rapid cycling. Divalproex treatment produced
      statistically significant improvement in MADRS scores compared with placebo from
      week 3 onward. The proportions of patients meeting response criteria were 38.5%
      (10 of 26) in the divalproex group versus 10.7% (3 of 28) for the placebo group
      (P = .017). The proportions of patients meeting remission criteria were 23.1% (6
      of 26) for divalproex versus 10.7% (3 of 28) for placebo (P = .208). Subgroup
      analysis revealed no separation between divalproex and placebo for those with
      bipolar II diagnoses. Nausea, increased appetite, diarrhea, dry mouth, and cramps
      were the most common side effects. CONCLUSIONS: These data suggest that
      divalproex sodium is efficacious and reasonably well tolerated in the acute
      treatment of mood stabilizer-naive patients with bipolar depression, particularly
      for those with rapid-cycling type I presentations, and that confirmatory large
      scale studies are indicated. TRIAL REGISTRATION: Clinicaltrials.gov Identifier:
      NCT00194116.

PMID- 20816042
TI  - Armodafinil as adjunctive therapy in adults with cognitive deficits associated
      with schizophrenia: a 4-week, double-blind, placebo-controlled study.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of armodafinil, the longer
      lasting isomer of modafinil, as adjunctive therapy in patients with
      schizophrenia. METHOD: This 4-week, randomized, double-blind, placebo-controlled,
      proof-of-concept study was conducted between July and December 2007. Patients had
      a history of stable schizophrenia (DSM-IV-TR criteria) for >= 8 weeks and were
      treated with oral risperidone, olanzapine, or paliperidone for >= 6 weeks at
      stable doses for >= 4 weeks. Patients were randomly assigned to once-daily
      placebo or armodafinil 50, 100, or 200 mg. The primary efficacy measure was the
      Measurement and Treatment Research to Improve Cognition in Schizophrenia
      (MATRICS) Consensus Cognitive Battery. Secondary outcome measures included the
      Positive and Negative Syndrome Scale (PANSS) and the Scale for Assessment of
      Negative Symptoms (SANS). RESULTS: Sixty patients were randomly assigned (15 in
      each group). No apparent differences between groups in the MATRICS composite
      score were observed (mean +/- SD change from baseline to final visit: armodafinil
      50 mg, 1.9 +/- 6.22; 100 mg, 2.8 +/- 7.98; 200 mg, 2.9 +/- 4.72; placebo, 2.2 +/-
      5.06). The mean +/- SD changes in PANSS total scores were -6.3 +/- 7.25 for
      armodafinil 200 mg and -1.7 +/- 4.89 for placebo at final visit (effect
      size=0.73; 95% CI, -0.08 to 1.54) and PANSS negative symptoms scores were -3.4 +/
      2.07 and 0.1 +/- 1.93 (effect size=1.69; 95% CI, 0.78 to 2.60), respectively.
      Although reductions in SANS total score were observed with both armodafinil and
      placebo at final visit, no between-group difference was shown. Armodafinil was
      generally well tolerated, with diarrhea and headache the most commonly reported
      adverse events. There was no evidence of worsening of psychosis with adjunctive
      armodafinil. CONCLUSIONS: In this 4-week study, adjunctive armodafinil was not
      associated with an improvement in cognitive measures, but armodafinil 200 mg/d
      appeared to mitigate the negative symptoms of schizophrenia. Treatment was
      generally well tolerated. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00487942.

PMID- 20816043
TI  - Contribution of long-range interactions to the secondary structure of an unfolded
      globin.
AB  - This work explores the effect of long-range tertiary contacts on the distribution
      of residual secondary structure in the unfolded state of an alpha-helical
      protein. N-terminal fragments of increasing length, in conjunction with
      multidimensional nuclear magnetic resonance, were employed. A protein
      representative of the ubiquitous globin fold was chosen as the model system. We
      found that, while most of the detectable alpha-helical population in the unfolded
      ensemble does not depend on the presence of the C-terminal region (corresponding
      to the native G and H helices), specific N-to-C long-range contacts between the H
      and A-B-C regions enhance the helical secondary structure content of the N
      terminus (A-B-C regions). The simple approach introduced here, based on the
      evaluation of N-terminal polypeptide fragments of increasing length, is of
      general applicability to identify the influence of long-range interactions in
      unfolded proteins.

PMID- 20816044
TI  - Catch-bond behavior of bacteria binding by slip bonds.
AB  - It is shown that multipili-adhering bacteria expressing helix-like pili binding
      by slip bonds can show catch-bond behavior. When exposed to an external force,
      such bacteria can mediate adhesion to their hosts by either of two limiting
      means: sequential or simultaneous pili force exposure (referring to when the pili
      mediate force in a sequential or simultaneous manner, respectively). As the force
      is increased, the pili can transition from sequential to simultaneous pili force
      exposure. Since the latter mode of adhesion gives rise to a significantly longer
      bacterial adhesion lifetime than the former, this results in a prolongation of
      the lifetime, which shows up as a catch-bond behavior. The properties and
      conditions of this effect were theoretically investigated and assessed in some
      detail for dual-pili-adhering bacteria, by both analytical means and simulations.
      The results indicate that the adhesion lifetime of such bacteria can be prolonged
      by more than an order of magnitude. This implies that the adhesion properties of
      multibinding systems cannot be directly conveyed to the individual adhesion
      receptor bonds.

PMID- 20816046
TI  - Exploring the paths of (virus) assembly.
AB  - Assembly of viruses that have hundreds of subunits or folding of proteins that
      have hundreds of amino acids-complex biological reactions-are often spontaneous
      and rapid. Here, we examine the complete set of intermediates available for the
      assembly of a hypothetical viruslike particle and the connectivity between these
      intermediates in a graph-theory-inspired study. Using a build-up procedure,
      assuming ideal geometry, we enumerated the complete set of 2,423,313 species for
      formation of an icosahedron from 30 dimeric subunits. Stability of each n-subunit
      intermediate was defined by the number of contacts between subunits. The
      probability of forming an intermediate was based on the number of paths to it
      from its precedecessors. When defining population subsets predicted to have the
      greatest impact on assembly, both stability- and probability-based criteria
      select a small group of compact and degenerate species; ergo, only a few hundred
      intermediates make a measurable contribution to assembly. Though the number of
      possible intermediates grows combinatorially with the number of subunits in the
      capsid, the number of intermediates that make a significant contribution to the
      reaction grows by a much smaller function, a result that may contribute to our
      understanding of assembly and folding reactions.

PMID- 20816045
TI  - Diffusion of particles in the extracellular matrix: the effect of repulsive
      electrostatic interactions.
AB  - Diffusive transport of macromolecules and nanoparticles in charged fibrous media
      is of interest in many biological applications, including drug delivery and
      separation processes. Experimental findings have shown that diffusion can be
      significantly hindered by electrostatic interactions between the diffusing
      particle and charged components of the extracellular matrix. The implications,
      however, have not been analyzed rigorously. Here, we present a mathematical
      framework to study the effect of charge on the diffusive transport of
      macromolecules and nanoparticles in the extracellular matrix of biological
      tissues. The model takes into account steric, hydrodynamic, and electrostatic
      interactions. We show that when the fiber size is comparable to the Debye length,
      electrostatic forces between the fibers and the particles result in slowed
      diffusion. However, as the fiber diameter increases the repulsive forces become
      less important. Our results explain the experimental observations that neutral
      particles diffuse faster than charged particles. Taken together, we conclude that
      optimal particles for delivery to tumors should be initially cationic to target
      the tumor vessels and then change to neutral charge after exiting the blood
      vessels.

PMID- 20816047
TI  - Localization microscopy reveals expression-dependent parameters of chromatin
      nanostructure.
AB  - A combined approach of 2D high-resolution localization light microscopy and
      statistical methods is presented to infer structural features and density
      fluctuations at the nuclear nanoscale. Hallmarks of nuclear nanostructure are
      found on the scale below 100 nm for both human fibroblast and HeLa cells.
      Mechanical measures were extracted as a quantitative tool from the histone
      density fluctuations inside the cell to obtain structural fluctuations on the
      scale of several micrometers. Results show that different mechanisms of
      expression of the same nuclear protein type lead to significantly different
      patterns on the nanoscale and to pronounced differences in the detected
      compressibility of chromatin. The observed fluctuations, including the
      experimental evidence for dynamic looping, are consistent with a recently
      proposed chromatin model.

PMID- 20816048
TI  - Analysis of microscopic parameters of single-particle trajectories in neurons.
AB  - We performed a comparative study of the statistical uncertainties that arise when
      calculating the velocity and diffusion coefficients from single-particle
      trajectories. We show that a method where particle mean displacement is used to
      calculate velocity and mean square fluctuation is used to calculate diffusion
      coefficient offers greater accuracy than analysis of time-dependent mean square
      displacement. Our assessment of the performance of the two analysis strategies is
      conducted in two ways. First, we apply each of the methods to simulated
      trajectories where each parameter term is known. Second, we analyze the motion of
      previously uncharacterized EphB2 receptors in the membrane of hippocampal
      neurons. We find that EphB2 receptors display different types of motion mode and
      transition between these modes. We present our data as a distribution of
      microscopic diffusion coefficients for each particle trajectory, which we refer
      to as partial distributions. Partial distributions are summed to form a
      cumulative distribution of diffusion coefficients for EphB2 receptors in
      hippocampal neurons. The structure and interpretation of the EphB2 cumulative
      distribution are discussed.

PMID- 20816049
TI  - Control of Ca2+ release by action potential configuration in normal and failing
      murine cardiomyocytes.
AB  - Cardiomyocytes from failing hearts exhibit spatially nonuniform or dyssynchronous
      sarcoplasmic reticulum (SR) Ca(2+) release. We investigated the contribution of
      action potential (AP) prolongation in mice with congestive heart failure (CHF)
      after myocardial infarction. AP recordings from CHF and control myocytes were
      included in a computational model of the dyad, which predicted more
      dyssynchronous ryanodine receptor opening during stimulation with the CHF AP.
      This prediction was confirmed in cardiomyocyte experiments, when cells were
      alternately stimulated by control and CHF AP voltage-clamp waveforms. However,
      when a train of like APs was used as the voltage stimulus, the control and CHF AP
      produced a similar Ca(2+) release pattern. In this steady-state condition,
      greater integrated Ca(2+) entry during the CHF AP lead to increased SR Ca(2+)
      content. A resulting increase in ryanodine receptor sensitivity synchronized SR
      Ca(2+) release in the mathematical model, thus offsetting the desynchronizing
      effects of reduced driving force for Ca(2+) entry. A modest nondyssynchronous
      prolongation of Ca(2+) release was nevertheless observed during the steady-state
      CHF AP, which contributed to increased time-to-peak measurements for Ca(2+)
      transients in failing cells. Thus, dyssynchronous Ca(2+) release in failing mouse
      myocytes does not result from electrical remodeling, but rather other alterations
      such as T-tubule reorganization.

PMID- 20816050
TI  - Temperature modulation of integrin-mediated cell adhesion.
AB  - In response to external stimuli, cells modulate their adhesive state by
      regulating the number and intrinsic affinity of receptor/ligand bonds. A number
      of studies have shown that cell adhesion is dramatically reduced at room or lower
      temperatures as compared with physiological temperature. However, the underlying
      mechanism that modulates adhesion is still unclear. Here, we investigated the
      adhesion of the monocytic cell line THP-1 to a surface coated with intercellular
      adhesion molecule-1 (ICAM-1) as a function of temperature. THP-1 cells express
      the integrin lymphocyte function-associated antigen-1 (LFA-1), a receptor for
      ICAM-1. Direct force measurements of cell adhesion and cell elasticity were
      carried out by atomic force microscopy. Force measurements revealed an increase
      of the work of de-adhesion with temperature that was coupled to a gradual
      decrease in cellular stiffness. Of interest, single-molecule measurements
      revealed that the rupture force of the LFA-1/ICAM-1 complex decreased with
      temperature. A detailed analysis of the force curves indicated that temperature
      modulated cell adhesion was mainly due to the enhanced ability of cells to deform
      and to form a greater number of longer membrane tethers at physiological
      temperatures. Together, these results emphasize the importance of cell mechanics
      and membrane-cytoskeleton interaction on the modulation of cell adhesion.

PMID- 20816051
TI  - Cholesterol depletion mimics the effect of cytoskeletal destabilization on
      membrane dynamics of the serotonin1A receptor: A zFCS study.
AB  - Single-point fluorescence correlation spectroscopy (FCS) of membrane-bound
      molecules suffers from a number of limitations leading to inaccurate estimation
      of diffusion parameters. To overcome such problems and with the overall goal of
      addressing membrane heterogeneities, we performed z-scan FCS (zFCS) of the
      serotonin(1A) receptor. We analyzed the results according to FCS diffusion laws
      that provide information on the organization of the diffusing species. Analysis
      of our results shows that the diffusion coefficients of the receptor and a
      fluorescently labeled phospholipid are similar when probed at length scales
      approximately 210 nm. We discuss the significance of the spatiotemporal evolution
      of dynamics of membrane-bound molecules in the overall context of membrane
      domains and heterogeneity. Importantly, our results show that the serotonin(1A)
      receptor exhibits confinement in cell membranes, possibly due to interaction with
      the actin cytoskeleton. Surprisingly, depletion of membrane cholesterol appears
      to reduce receptor confinement in a manner similar to that observed in the case
      of cytoskeletal destabilization, implying possible changes in the actin
      cytoskeleton induced upon cholesterol depletion. These results constitute the
      first report on G-protein-coupled receptor dynamics utilizing a combination of
      zFCS and the FCS diffusion laws, and present a convenient approach to explore
      cell membrane heterogeneity at the submicron level.

PMID- 20816052
TI  - So little source, so much sink: requirements for afterdepolarizations to
      propagate in tissue.
AB  - How early (EADs) and delayed afterdepolarizations (DADs) overcome electrotonic
      source-sink mismatches in tissue to trigger premature ventricular complexes
      remains incompletely understood. To study this question, we used a rabbit
      ventricular action potential model to simulate tissues in which a central area of
      contiguous myocytes susceptible to EADs or DADs was surrounded by unsusceptible
      tissue. In 1D tissue with normal longitudinal conduction velocity (0.55 m/s), the
      numbers of contiguous susceptible myocytes required for an EAD and a barely
      suprathreshold DAD to trigger a propagating action potential were 70 and 80,
      respectively. In 2D tissue, these numbers increased to 6940 and 7854, and in 3D
      tissue to 696,910 and 817,280. These numbers were significantly decreased by
      reduced gap junction conductance, simulated fibrosis, reduced repolarization
      reserve and heart failure electrical remodeling. In conclusion, the source-sink
      mismatch in well-coupled cardiac tissue powerfully protects the heart from
      arrhythmias due to sporadic afterdepolarizations. Structural and
      electrophysiological remodeling decrease these numbers significantly but still
      require synchronization mechanisms for EADs and DADs to overcome the robust
      protective effects of source-sink mismatch.

PMID- 20816053
TI  - Identification of the third Na+ site and the sequence of extracellular binding
      events in the glutamate transporter.
AB  - The transport cycle in the glutamate transporter (GlT) is catalyzed by the
      cotransport of three Na(+) ions. However, the positions of only two of these ions
      (Na1 and Na2 sites) along with the substrate have been captured in the crystal
      structures reported for both the outward-facing and the inward-facing states of
      Glt(ph). Characterizing the third ion binding site (Na3) is necessary for
      structure-function studies attempting to investigate the mechanism of transport
      in GlTs at an atomic level, particularly for the determination of the sequence of
      the binding events during the transport cycle. In this study, we report a series
      of molecular dynamics simulations performed on various bound states of Glt(ph)
      (the apo state, as well as in the presence of Na(+), the substrate, or both),
      which have been used to identify a putative Na3 site. The calculated trajectories
      have been used to determine the water accessibility of potential ion-binding
      residues in the protein, as a prerequisite for their ion binding. Combined with
      conformational analysis of the key regions in the protein in different bound
      states and several additional independent simulations in which a Na(+) ion was
      randomly introduced to the interior of the transporter, we have been able to
      characterize a putative Na3 site and propose a plausible binding sequence for the
      substrate and the three Na(+) ions to the transporter during the extracellular
      half of the transport cycle. The proposed Na3 site is formed by a set of highly
      conserved residues, namely, Asp(312), Thr(92), and Asn(310), along with a water
      molecule. Simulation of a fully bound state, including the substrate and the
      three Na(+) ions, reveals a stable structure--showing closer agreement to the
      crystal structure when compared to previous models lacking an ion in the putative
      Na3 site. The proposed sequence of binding events is in agreement with recent
      experimental models suggesting that two Na(+) ions bind before the substrate, and
      one after that. Our results, however, provide additional information about the
      sites involved in these binding events.

PMID- 20816054
TI  - Kinetics and regulation of mammalian NADH-ubiquinone oxidoreductase (Complex I).
AB  - NADH-ubiquinone oxidoreductase (Complex I, European Commission No. 1.6.5.3) is
      one of the respiratory complexes that generate the proton-motive force required
      for the synthesis of ATP in mitochondria. The catalytic mechanism of Complex I
      has not been well understood, due to the complicated structure of this enzyme.
      Here, we develop a kinetic model for Complex I that accounts for electron
      transfer from NADH to ubiquinone through protein-bound prosthetic groups, which
      is coupled to the translocation of protons across the inner mitochondrial
      membrane. The model is derived based on the tri-bi enzyme mechanism combined with
      a simple model of the conformational changes associated with proton transport. To
      study the catalytic mechanism, parameter values are estimated by analyzing
      kinetic data. The model is further validated by independent data sets from
      additional experiments, effectively explaining the effect of pH on enzyme
      activity. Results imply that matrix pH significantly affects the enzyme turnover
      processes. The overall kinetic analysis demonstrates a hybrid ping-pong rapid
      equilibrium random bi-bi mechanism, consolidating the characteristics from
      previously reported kinetic mechanisms and data.

PMID- 20816055
TI  - Characterizing single-channel behavior of GluA3 receptors.
AB  - AMPA receptors play a major role in excitatory neurotransmission in the CNS and
      are involved in numerous neurological disorders. Agonists bind to each of four
      bilobed LBDs of this tetrameric receptor, and upon binding, the lobes close to
      envelope the agonist, leading to channel activation. However, AMPA receptors
      exhibit complex activation kinetics, the mechanism of which has not yet been
      determined. We report here single-channel studies of a homomeric AMPA receptor
      (GluA3) activated by the full agonist, glutamate, and a partial agonist,
      fluorowillardiine. Both agonists activate the channel to the same three open
      conductance levels but with different open probabilities in each level. The
      closed probability (P(c)) varied within records, particularly at low agonist
      concentrations. By sorting discrete segments of the record according to P(c)
      using the X-means algorithm, we defined five modes of activity. The kinetic
      behavior could then be analyzed for both agonists over a range of agonist
      concentrations with a relatively simple model (three closed states and two open
      states for each open conductance level). The structural mechanism underlying the
      modal behavior is not clear; however, it occurs on a timescale consistent with
      hydrogen bonding across the lobe interface in the LBD.

PMID- 20816056
TI  - Influence of hydrophobic mismatch and amino acid composition on the lateral
      diffusion of transmembrane peptides.
AB  - We investigated the effect of amino acid composition and hydrophobic length of
      alpha-helical transmembrane peptides and the role of electrostatic interactions
      on the lateral diffusion of the peptides in lipid membranes. Model peptides of
      varying length and composition, and either tryptophans or lysines as flanking
      residues, were synthesized. The peptides were labeled with the fluorescent label
      Alexa Fluor 488 and incorporated into phospholipid bilayers of different
      hydrophobic thickness and composition. Giant unilamellar vesicles were formed by
      electroformation, and the lateral diffusion of the transmembrane peptides (and
      lipids) was determined by fluorescence correlation spectroscopy. In addition, we
      performed coarse-grained molecular-dynamics simulations of single peptides of
      different hydrophobic lengths embedded in planar membranes of different
      thicknesses. Both the experimental and simulation results indicate that lateral
      diffusion is sensitive to membrane thickness between the peptides and surrounding
      lipids. We did not observe a difference in the lateral diffusion of the peptides
      with respect to the presence of tryptophans or lysines as flanking residues. The
      specific lipid headgroup composition of the membrane has a much less pronounced
      impact on the diffusion of the peptides than does the hydrophobic thickness.

PMID- 20816057
TI  - Interpretation of 2H-NMR experiments on the orientation of the transmembrane
      helix WALP23 by computer simulations.
AB  - Orientation, dynamics, and packing of transmembrane helical peptides are
      important determinants of membrane protein structure, dynamics, and function.
      Because it is difficult to investigate these aspects by studying real membrane
      proteins, model transmembrane helical peptides are widely used. NMR experiments
      provide information on both orientation and dynamics of peptides, but they
      require that motional models be interpreted. Different motional models yield
      different interpretations of quadrupolar splittings (QS) in terms of helix
      orientation and dynamics. Here, we use coarse-grained (CG) molecular dynamics
      (MD) simulations to investigate the behavior of a well-known model transmembrane
      peptide, WALP23, under different hydrophobic matching/mismatching conditions. We
      compare experimental (2)H-NMR QS (directly measured in experiments), as well as
      helix tilt angle and azimuthal rotation (not directly measured), with CG MD
      simulation results. For QS, the agreement is significantly better than previously
      obtained with atomistic simulations, indicating that equilibrium sampling is more
      important than atomistic details for reproducing experimental QS. Calculations of
      helix orientation confirm that the interpretation of QS depends on the motional
      model used. Our simulations suggest that WALP23 can form dimers, which are more
      stable in an antiparallel arrangement. The origin of the preference for the
      antiparallel orientation lies not only in electrostatic interactions but also in
      better surface complementarity. In most cases, a mixture of monomers and
      antiparallel dimers provides better agreement with NMR data compared to the
      monomer and the parallel dimer. CG MD simulations allow predictions of helix
      orientation and dynamics and interpretation of QS data without requiring any
      assumption about the motional model.

PMID- 20816058
TI  - Structure and dynamics of the membrane-bound form of Pf1 coat protein:
      implications of structural rearrangement for virus assembly.
AB  - The three-dimensional structure of the membrane-bound form of the major coat
      protein of Pf1 bacteriophage was determined in phospholipid bilayers using
      orientation restraints derived from both solid-state and solution NMR
      experiments. In contrast to previous structures determined solely in detergent
      micelles, the structure in bilayers contains information about the spatial
      arrangement of the protein within the membrane, and thus provides insights to the
      bacteriophage assembly process from membrane-inserted to bacteriophage-associated
      protein. Comparisons between the membrane-bound form of the coat protein and the
      previously determined structural form found in filamentous bacteriophage
      particles demonstrate that it undergoes a significant structural rearrangement
      during the membrane-mediated virus assembly process. The rotation of the
      transmembrane helix (Q16-A46) around its long axis changes dramatically (by 160
      degrees) to obtain the proper alignment for packing in the virus particles.
      Furthermore, the N-terminal amphipathic helix (V2-G17) tilts away from the
      membrane surface and becomes parallel with the transmembrane helix to form one
      nearly continuous long helix. The spectra obtained in glass-aligned planar lipid
      bilayers, magnetically aligned lipid bilayers (bicelles), and isotropic lipid
      bicelles reflect the effects of backbone motions and enable the backbone dynamics
      of the N-terminal helix to be characterized. Only resonances from the mobile N
      terminal helix and the C-terminus (A46) are observed in the solution NMR spectra
      of the protein in isotropic q > 1 bicelles, whereas only resonances from the
      immobile transmembrane helix are observed in the solid-state (1)H/(15)N-separated
      local field spectra in magnetically aligned bicelles. The N-terminal helix and
      the hinge that connects it to the transmembrane helix are significantly more
      dynamic than the rest of the protein, thus facilitating structural rearrangement
      during bacteriophage assembly.

PMID- 20816059
TI  - Effects of beta-cyclodextrin on the structure of sphingomyelin/cholesterol model
      membranes.
AB  - The interaction of beta-cyclodextrin (beta-CD) with mixed bilayers composed of
      sphingomylein and cholesterol (Chol) above and below the accepted stable
      complexation ratio (67:33) was investigated. Membranes with the same (symmetric)
      and different (asymmetric) compositions in their inner and outer leaflets were
      deposited at surface pressures of 20, 30, and 40 mN/m at the solid-liquid
      interface. Using neutron reflectometry, membranes of various global molar ratios
      (defined as the sum of the molar ratios of the inner and outer leaflets), were
      characterized before and after beta-CD was added to the subphase. The structure
      of bilayers with global molar ratios at or above the stable complexation ratio
      was unchanged by beta-CD, indicating that beta-CD is unable to remove
      sphingomyelin or complexed Chol. However, beta-CD removed all uncomplexed Chol
      from bilayers composed of global molar ratios below the stable complexation
      ratio. The removal of Chol by beta-CD was independent of the initial structure of
      the membranes as deposited, suggesting that asymmetric membranes homogenize by
      the exchange of molecules between leaflets. The interaction of beta-CD with the
      aforementioned membranes was independent of the deposition surface pressure
      except for a symmetric 50:50 membrane deposited at 40 mN/m. The scattering from
      50:50 bilayers with higher packing densities (deposited at 40 mN/m) was
      unaffected by beta-CD, suggesting that the removal of Chol can depend on both the
      composition and packing density of the membrane.

PMID- 20816061
TI  - Two-dimensional continuum percolation threshold for diffusing particles of
      nonzero radius.
AB  - Lateral diffusion in the plasma membrane is obstructed by proteins bound to the
      cytoskeleton. The most important parameter describing obstructed diffusion is the
      percolation threshold. The thresholds are well known for point tracers, but for
      tracers of nonzero radius, the threshold depends on the excluded area, not just
      the obstacle concentration. Here thresholds are obtained for circular obstacles
      on the continuum. Random obstacle configurations are generated by Brownian
      dynamics or Monte Carlo methods, the obstacles are immobilized, and the
      percolation threshold is obtained by solving a bond percolation problem on the
      Voronoi diagram of the obstacles. The percolation threshold is expressed as the
      diameter of the largest tracer that can cross a set of immobile obstacles at a
      prescribed number density. For random overlapping obstacles, the results agree
      with the known analytical solution quantitatively. When the obstacles are soft
      disks with a 1/r(12) repulsion, the percolating diameter is approximately 20%
      lower than for overlapping obstacles. A percolation model predicts that the
      threshold is highly sensitive to the tracer radius. To our knowledge, such a
      strong dependence has so far not been reported for the plasma membrane,
      suggesting that percolation is not the factor controlling lateral diffusion. A
      definitive experiment is proposed.

PMID- 20816060
TI  - Lateral diffusion of membrane proteins: consequences of hydrophobic mismatch and
      lipid composition.
AB  - Biological membranes are composed of a large number lipid species differing in
      hydrophobic length, degree of saturation, and charge and size of the headgroup.
      We now present data on the effect of hydrocarbon chain length of the lipids and
      headgroup composition on the lateral mobility of the proteins in model membranes.
      The trimeric glutamate transporter (GltT) and the monomeric lactose transporter
      (LacY) were reconstituted in giant unilamellar vesicles composed of unsaturated
      phosphocholine lipids of varying acyl chain length (14-22 carbon atoms) and
      various ratios of DOPE/DOPG/DOPC lipids. The lateral mobility of the proteins and
      of a fluorescent lipid analog was determined as a function of the hydrophobic
      thickness of the bilayer (h) and lipid composition, using fluorescence
      correlation spectroscopy. The diffusion coefficient of LacY decreased with
      increasing thickness of the bilayer, in accordance with the continuum
      hydrodynamic model of Saffman-Delbruck. For GltT, the mobility had its maximum at
      diC18:1 PC, which is close to the hydrophobic thickness of the bilayer in vivo.
      The lateral mobility decreased linearly with the concentration of DOPE but was
      not affected by the fraction of anionic lipids from DOPG. The addition of DOPG
      and DOPE did not affect the activity of GltT. We conclude that the hydrophobic
      thickness of the bilayer is a major determinant of molecule diffusion in
      membranes, but protein-specific properties may lead to deviations from the
      Saffman-Delbruck model.

PMID- 20816062
TI  - Equivalent aqueous phase modulation of domain segregation in myelin monolayers
      and bilayer vesicles.
AB  - Purified myelin can be spread as monomolecular films at the air/aqueous
      interface. These films were visualized by fluorescence and Brewster angle
      microscopy, showing phase coexistence at low and medium surface pressures (<20-30
      mN/m). Beyond this threshold, the film becomes homogeneous or not, depending on
      the aqueous subphase composition. Pure water as well as sucrose, glycerol,
      dimethylsulfoxide, and dimethylformamide solutions (20% in water) produced
      monolayers that become homogeneous at high surface pressures; on the other hand,
      the presence of salts (NaCl, CaCl(2)) in Ringer's and physiological solution
      leads to phase domain microheterogeneity over the whole compression isotherm.
      These results show that surface heterogeneity is favored by the ionic milieu. The
      modulation of the phase-mixing behavior in monolayers is paralleled by the
      behavior of multilamellar vesicles as determined by small-angle and wide-angle x
      ray scattering. The correspondence of the behavior of monolayers and multilayers
      is achieved only at high surface pressures near the equilibrium adsorption
      surface pressure; at lower surface pressures, the correspondence breaks down. The
      equilibrium surface tension on all subphases corresponds to that of the
      air/alkane interface (27 mN/m), independently on the surface tension of the clean
      subphase.

PMID- 20816063
TI  - Designed fluorescent probes reveal interactions between amyloid-beta(1-40)
      peptides and GM1 gangliosides in micelles and lipid vesicles.
AB  - A hallmark of the common Alzheimer's disease (AD) is the pathological conversion
      of its amphiphatic amyloid-beta (Abeta) peptide into neurotoxic aggregates. In AD
      patients, these aggregates are often found to be tightly associated with neuronal
      G(M1) ganglioside lipids, suggesting an involvement of G(M1) not only in
      aggregate formation but also in neurotoxic events. Significant interactions were
      found between micelles made of newly synthesized fluorescent G(M1) gangliosides
      labeled in the polar headgroup or the hydrophobic chain and Abeta(1-40) peptide
      labeled with a BODIPY-FL-C1 fluorophore at positions 12 and 26, respectively.
      From an analysis of energy transfer between the different fluorescence labels and
      their location in the molecules, we were able to place the Abeta peptide inside
      G(M1) micelles, close to the hydrophobic-hydrophilic interface. Large unilamellar
      vesicles composed of a raftlike G(M1)/bSM/cholesterol lipid composition doped
      with labeled G(M1) at various positions also interact with labeled Abeta peptide
      tagged to amino acids 2 or 26. A faster energy transfer was observed from the
      Abeta peptide to bilayers doped with 581/591-BODIPY-C(11)-G(M1) in the nonpolar
      part of the lipid compared with 581/591-BODIPY-C(5)-G(M1) residing in the polar
      headgroup. These data are compatible with a clustering process of G(M1)
      molecules, an effect that not only increases the Abeta peptide affinity, but also
      causes a pronounced Abeta peptide penetration deeper into the lipid membrane; all
      these factors are potentially involved in Abeta peptide aggregate formation due
      to an altered ganglioside metabolism found in AD patients.

PMID- 20816064
TI  - Self-reproduction of fatty acid vesicles: a combined experimental and simulation
      study.
AB  - Dilution of a fatty acid micellar solution at basic pH toward neutrality results
      in spontaneous formation of vesicles with a broad size distribution. However,
      when vesicles of a defined size are present before dilution, the size
      distribution of the newly formed vesicles is strongly biased toward that of the
      seed vesicles. This so-called matrix effect is believed to be a key feature of
      early life. Here we reproduced this effect for oleate micelles and seed vesicles
      of either oleate or dioleoylphosphatidylcholine. Fluorescence measurements showed
      that the vesicle contents do not leak out during the replication process. We
      hypothesized that the matrix effect results from vesicle fission induced by an
      imbalance of material across both leaflets of the vesicle upon initial insertion
      of fatty acids into the outer leaflet of the seed vesicle. This was supported by
      experiments that showed a significant increase in vesicle size when the
      equilibration of oleate over both leaflets was enhanced by either slowing down
      the rate of fatty acid addition or increasing the rate of fatty acid transbilayer
      movement. Coarse-grained molecular-dynamics simulations showed excellent
      agreement with the experimental results and provided further mechanistic details
      of the replication process.

PMID- 20816065
TI  - Chemical versus mechanical perturbations on the protonation state of arginine in
      complex lipid membranes: insights from microscopic pKa calculations.
AB  - Charged amino acids such as Arginine play important roles in many membrane
      mediated biological processes such as voltage gating of ion channels and membrane
      translocation of cell penetration peptides. It is well established that local
      membrane deformation and formation of water defects are crucial to the
      stabilization of charged species in contact with the membrane, which suggests
      that mechanical properties of the membrane are relevant although a clear
      connection has not been established. As a quantitative measure, we study how
      changes in the composition and therefore mechanical properties of a lipid bilayer
      influence the pK(a) of Arg in the membrane center using free energy simulations.
      Compared to previous studies in a single-component lipid bilayer containing
      saturated lipids or lipids with a modest degree of unsaturation, substantially
      larger pK(a) shifts are observed in the presence of highly unsaturated lipid
      tails and cholesterol. Moreover, the underlying molecular mechanisms for the
      pK(a) perturbation are distinct in different systems, with the unsaturated lipid
      tails mainly destabilizing the charged state of Arg and the cholesterol
      stabilizing the neutral state of Arg. The observed behaviors in both cases are at
      odds with predictions based on mechanical considerations at a mesoscopic level-
      highlighting that, while mechanical considerations are useful for stimulating
      hypothesis, their applicability to dissecting phenomena at the molecular-length
      scale is rather limited.

PMID- 20816066
TI  - The vesicle trafficking protein Sar1 lowers lipid membrane rigidity.
AB  - The sculpting of membranes into dynamic, curved shapes is central to
      intracellular cargo trafficking. Though the generation of membrane curvature
      during trafficking necessarily involves both lipids and membrane-associated
      proteins, current mechanistic views focus primarily on the formation of rigid
      cages and curved scaffolds by protein assemblies. Here we report on a different
      mechanism for the control of membrane deformation, unrelated to the imposition of
      predefined curvature, involving modulation of membrane material properties: Sar1,
      a GTPase that regulates vesicle trafficking from the endoplasmic reticulum,
      lowers the rigidity of the lipid bilayer membrane to which it binds. In vitro
      assays in which optically trapped microspheres create controlled membrane
      deformations revealed a monotonic decline in bending modulus as a function of
      Sar1 concentration, down to nearly zero rigidity, indicating a dramatic lowering
      of the energetic cost of curvature generation. This is the first demonstration
      that a vesicle trafficking protein lowers the rigidity of its target membrane,
      leading to a new conceptual framework for vesicle biogenesis.

PMID- 20816067
TI  - The influence of myosin converter and relay domains on cross-bridge kinetics of
      Drosophila indirect flight muscle.
AB  - We are investigating the influence of the converter and relay domains on
      elementary rate constants of the actomyosin cross-bridge cycle. The converter and
      relay domains vary between Drosophila myosin heavy chain isoforms due to
      alternative mRNA splicing. Previously, we found that separate insertions of
      embryonic myosin isoform (EMB) versions of these domains into the indirect flight
      muscle (IFM) myosin isoform (IFI) both decreased Drosophila IFM power and slowed
      muscle kinetics. To determine cross-bridge mechanisms behind the changes, we
      employed sinusoidal analysis while varying phosphate and MgATP concentrations in
      skinned Drosophila IFM fibers. Based on a six-state cross-bridge model, the EMB
      converter decreased myosin rate constants associated with actin attachment and
      work production, k(4), but increased rates related to cross-bridge detachment and
      work absorption, k(2). In contrast, the EMB relay domain had little influence on
      kinetics, because only k(4) decreased. The main alteration was mechanical, in
      that work production amplitude decreased. That both domains decreased k(4)
      supports the hypothesis that these domains are critical to lever-arm-mediated
      force generation. Neither domain significantly influenced MgATP affinity. Our
      modeling suggests the converter domain is responsible for the difference in rate
      limiting cross-bridge steps between EMB and IFI myosin--i.e., a myosin
      isomerization associated with MgADP release for EMB and Pi release for IFI.

PMID- 20816068
TI  - Increased store-operated Ca2+ entry in skeletal muscle with reduced calsequestrin
      1 expression.
AB  - Store-operated Ca(2+) entry (SOCE) contributes to Ca(2+) handling in normal
      skeletal muscle function, as well as the progression of muscular dystrophy and
      sarcopenia, yet the mechanisms underlying the change in SOCE in these states
      remain unclear. Previously we showed that calsequestrin-1 (CSQ1) participated in
      retrograde regulation of SOCE in cultured skeletal myotubes. In this study, we
      used small-hairpin RNA to determine whether knockdown of CSQ1 in adult mouse
      skeletal muscle can influence SOCE activity and muscle function. Small-hairpin
      RNA against CSQ1 was introduced into flexor digitorum brevis muscles using
      electroporation. Transfected fibers were isolated for SOCE measurements using the
      Mn(2+) fluorescence-quenching method. At room temperature, the SOCE induced by
      submaximal depletion of the SR Ca(2+) store was significantly enhanced in CSQ1
      knockdown muscle fibers. When temperature of the bathing solution was increased
      to 39 degrees C, CSQ1-knockdown muscle fibers displayed a significant increase in
      Ca(2+) permeability across the surface membrane likely via the SOCE pathway, and
      a corresponding elevation in cytosolic Ca(2+) as compared to control fibers.
      Preincubation with azumolene, an analog of dantrolene used for the treatment of
      malignant hyperthermia (MH), suppressed the elevated SOCE in CSQ1-knockdown
      fibers. Because the CSQ1-knockout mice develop similar MH phenotypes, this
      inhibitory effect of azumolene on SOCE suggests that elevated extracellular
      Ca(2+) entry in skeletal muscle may be a key factor for the pathophysiological
      changes in intracellular Ca(2+) signaling in MH.

PMID- 20816069
TI  - Predicting ion binding properties for RNA tertiary structures.
AB  - Recent experiments pointed to the potential importance of ion correlation for
      multivalent ions such as Mg(2+) ions in RNA folding. In this study, we develop an
      all-atom model to predict the ion electrostatics in RNA folding. The model can
      treat ion correlation effects explicitly by considering an ensemble of discrete
      ion distributions. In contrast to the previous coarse-grained models that can
      treat ion correlation, this new model is based on all-atom nucleic acid
      structures. Thus, unlike the previous coarse-grained models, this new model
      allows us to treat complex tertiary structures such as HIV-1 DIS type RNA kissing
      complexes. Theory-experiment comparisons for a variety of tertiary structures
      indicate that the model gives improved predictions over the Poisson-Boltzmann
      theory, which underestimates the Mg(2+) binding in the competition with Na(+).
      Further systematic theory-experiment comparisons for a series of tertiary
      structures lead to a set of analytical formulas for Mg(2+)/Na(+) ion-binding to
      various RNA and DNA structures over a wide range of Mg(2+) and Na(+)
      concentrations.

PMID- 20816070
TI  - Charge state of the globular histone core controls stability of the nucleosome.
AB  - Presented here is a quantitative model of the wrapping and unwrapping of the DNA
      around the histone core of the nucleosome that suggests a mechanism by which this
      transition can be controlled: alteration of the charge state of the globular
      histone core. The mechanism is relevant to several classes of posttranslational
      modifications such as histone acetylation and phosphorylation; several specific
      scenarios consistent with recent in vivo experiments are considered. The model
      integrates a description based on an idealized geometry with one based on the
      atomistic structure of the nucleosome, and the model consistently accounts for
      both the electrostatic and nonelectrostatic contributions to the nucleosome free
      energy. Under physiological conditions, isolated nucleosomes are predicted to be
      very stable (38 +/- 7 kcal/mol). However, a decrease in the charge of the
      globular histone core by one unit charge, for example due to acetylation of a
      single lysine residue, can lead to a significant decrease in the strength of
      association with its DNA. In contrast to the globular histone core, comparable
      changes in the charge state of the histone tail regions have relatively little
      effect on the nucleosome's stability. The combination of high stability and
      sensitivity explains how the nucleosome is able to satisfy the seemingly
      contradictory requirements for thermodynamic stability while allowing quick
      access to its DNA informational content when needed by specific cellular
      processes such as transcription.

PMID- 20816071
TI  - Internal binding of halogenated phenols in dehaloperoxidase-hemoglobin inhibits
      peroxidase function.
AB  - Dehaloperoxidase (DHP) from the annelid Amphitrite ornata is a catalytically
      active hemoglobin-peroxidase that possesses a unique internal binding cavity in
      the distal pocket above the heme. The previously published crystal structure of
      DHP shows 4-iodophenol bound internally. This led to the proposal that the
      internal binding site is the active site for phenol oxidation. However, the
      native substrate for DHP is 2,4,6-tribromophenol, and all attempts to bind 2,4,6
      tribromophenol in the internal site under physiological conditions have failed.
      Herein, we show that the binding of 4-halophenols in the internal pocket inhibits
      enzymatic function. Furthermore, we demonstrate that DHP has a unique two-site
      competitive binding mechanism in which the internal and external binding sites
      communicate through two conformations of the distal histidine of the enzyme,
      resulting in nonclassical competitive inhibition. The same distal histidine
      conformations involved in DHP function regulate oxygen binding and release during
      transport and storage by hemoglobins and myoglobins. This work provides further
      support for the hypothesis that DHP possesses an external binding site for
      substrate oxidation, as is typical for the peroxidase family of enzymes.

PMID- 20816072
TI  - An unusual hydrophobic core confers extreme flexibility to HEAT repeat proteins.
AB  - Alpha-solenoid proteins are suggested to constitute highly flexible
      macromolecules, whose structural variability and large surface area is
      instrumental in many important protein-protein binding processes. By equilibrium
      and nonequilibrium molecular dynamics simulations, we show that importin-beta, an
      archetypical alpha-solenoid, displays unprecedentedly large and fully reversible
      elasticity. Our stretching molecular dynamics simulations reveal full elasticity
      over up to twofold end-to-end extensions compared to its bound state. Despite the
      absence of any long-range intramolecular contacts, the protein can return to its
      equilibrium structure to within 3 A backbone RMSD after the release of mechanical
      stress. We find that this extreme degree of flexibility is based on an unusually
      flexible hydrophobic core that differs substantially from that of structurally
      similar but more rigid globular proteins. In that respect, the core of importin
      beta resembles molten globules. The elastic behavior is dominated by nonpolar
      interactions between HEAT repeats, combined with conformational entropic effects.
      Our results suggest that alpha-solenoid structures such as importin-beta may
      bridge the molecular gap between completely structured and intrinsically
      disordered proteins.

PMID- 20816073
TI  - Conformational exchange in a membrane transport protein is altered in protein
      crystals.
AB  - Successful macromolecular crystallography requires solution conditions that may
      alter the conformational sampling of a macromolecule. Here, site-directed spin
      labeling is used to examine a conformational equilibrium within BtuB, the
      Escherichia coli outer membrane transporter for vitamin B(12). Electron
      paramagnetic resonance (EPR) spectra from a spin label placed within the N
      terminal energy coupling motif (Ton box) of BtuB indicate that this segment is in
      equilibrium between folded and unfolded forms. In bilayers, substrate binding
      shifts this equilibrium toward the unfolded form; however, EPR spectra from this
      same spin-labeled mutant indicate that this unfolding transition is blocked in
      protein crystals. Moreover, crystal structures of this spin-labeled mutant are
      consistent with the EPR result. When the free energy difference between substates
      is estimated from the EPR spectra, the crystal environment is found to alter this
      energy by 3 kcal/mol when compared to the bilayer state. Approximately half of
      this energy change is due to solutes or osmolytes in the crystallization buffer,
      and the remainder is contributed by the crystal lattice. These data provide a
      quantitative measure of how a conformational equilibrium in BtuB is modified in
      the crystal environment, and suggest that more-compact, less-hydrated substates
      will be favored in protein crystals.

PMID- 20816074
TI  - Modeling the hydration layer around proteins: HyPred.
AB  - Protein hydration plays an integral role in determining protein function and
      stability. We develop a simple method with atomic level precision for predicting
      the solvent density near the surface of a protein. A set of proximal radial
      distribution functions are defined and calculated for a series of different atom
      types in proteins using all-atom, explicit solvent molecular dynamic simulations
      for three globular proteins. A major improvement in predicting the hydration
      layer is found when the protein is held immobile during the simulations. The
      distribution functions are used to develop a model for predicting the hydration
      layer with sub-1-Angstrom resolution without the need for additional simulations.
      The model and the distribution functions for a given protein are tested in their
      ability to reproduce the hydration layer from the simulations for that protein,
      as well as those for other proteins and for simulations in which the protein
      atoms are mobile. Predictions for the density of water in the hydration shells
      are then compared with high occupancy sites observed in crystal structures. The
      accuracy of both tests demonstrates that the solvation model provides a basis for
      quantitatively understanding protein solvation and thereby predicting the
      hydration layer without additional simulations.

PMID- 20816075
TI  - Complex unfolding kinetics of single-domain proteins in the presence of force.
AB  - Single-molecule force spectroscopy is providing unique, and sometimes unexpected,
      insights into the free-energy landscapes of proteins. Despite the complexity of
      the free-energy landscapes revealed by mechanical probes, forced unfolding
      experiments are often analyzed using one-dimensional models that predict a
      logarithmic dependence of the unfolding force on the pulling velocity. We
      previously found that the unfolding force of the protein filamin at low pulling
      speed did not decrease logarithmically with the pulling speed. Here we present
      results from a large number of unfolding simulations of a coarse-grain model of
      the protein filamin under a broad range of constant forces. These show that a two
      path model is physically plausible and produces a deviation from the behavior
      predicted by one-dimensional models analogous to that observed experimentally. We
      also show that the analysis of the distributions of unfolding forces (p[F])
      contains crucial and exploitable information, and that a proper description of
      the unfolding of single-domain proteins needs to account for the intrinsic
      multidimensionality of the underlying free-energy landscape, especially when the
      applied perturbation is small.

PMID- 20816076
TI  - Refolding the engrailed homeodomain: structural basis for the accumulation of a
      folding intermediate.
AB  - The ultrafast folding pathway of the engrailed homeodomain has been exceptionally
      well characterized by experiment and simulation. Helices II and III of the three
      helix bundle protein form the native helix-turn-helix motif as an on-pathway
      intermediate within a few microseconds. The slow step is then the proper docking
      of the helices in approximately 15 mus. However, there is still the unexplained
      puzzle of why helix docking is relatively slow, which is part of the more general
      question as to why rearrangements of intermediates occur slowly. To address this
      problem, we performed 46 all-atom molecular dynamics refolding simulations in
      explicit water, for a total of 15 micros of simulation time. The simulations
      started from an intermediate state structure that was generated in an unfolding
      simulation at 498 K and was then quenched to folding-permissive temperatures. The
      protein refolded successfully in only one of the 46 simulations, and in that case
      the refolding pathway mirrored the unfolding pathway at high temperature. In the
      45 simulations in which the protein did not fully fold, nonnative salt bridges
      trapped the protein, which explains why the protein folds relatively slowly from
      the intermediate state.

PMID- 20816077
TI  - Hydrophobic core formation and dehydration in protein folding studied by
      generalized-ensemble simulations.
AB  - Despite its small size, chicken villin headpiece subdomain HP36 folds into the
      native structure with a stable hydrophobic core within several microseconds. How
      such a small protein keeps up its conformational stability and fast folding in
      solution is an important issue for understanding molecular mechanisms of protein
      folding. In this study, we performed multicanonical replica-exchange simulations
      of HP36 in explicit water, starting from a fully extended conformation. We
      observed at least five events of HP36 folding into nativelike conformations. The
      smallest backbone root mean-square deviation from the crystal structure was 1.1
      A. In the nativelike conformations, the stably formed hydrophobic core was fully
      dehydrated. Statistical analyses of the simulation trajectories show the
      following sequential events in folding of HP36: 1), Helix 3 is formed at the
      earliest stage; 2), the backbone and the side chains near the loop between
      Helices 2 and 3 take nativelike conformations; and 3), the side-chain packing at
      the hydrophobic core and the dehydration of the core side chains take place
      simultaneously at the later stage of folding. This sequence suggests that the
      initial folding nucleus is not necessarily the same as the hydrophobic core,
      consistent with a recent experimental phi-value analysis.

PMID- 20816078
TI  - A method for removing effects of nonspecific binding on the distribution of
      binding stoichiometries: application to mass spectroscopy data.
AB  - There is often an interest in knowing, for a given ligand concentration, how many
      protein molecules have one, two, three, etc. ligands bound in a specific manner.
      This is a question that cannot be addressed using conventional ensemble
      techniques. Here, a mathematical method is presented for separating specific from
      nonspecific binding in nonensemble studies. The method provides a way to
      determine the distribution of specific binding stoichiometries at any ligand
      concentration when using nonensemble (e.g., single-molecule) methods. The
      applicability of the method is demonstrated for ADP binding to creatine kinase
      using mass spectroscopy data. A major advantage of our method, which can be
      applied to any protein-ligand system, is that no previous information regarding
      the mechanism of ligand interaction is required.

PMID- 20816079
TI  - Rationale for more diverse inhibitors in competition with substrates in HIV-1
      protease.
AB  - The structural fluctuations of HIV-1 protease in interaction with its substrates
      versus inhibitors were analyzed using the anisotropic network model. The
      directions of fluctuations in the most cooperative functional modes differ mainly
      around the dynamically key regions, i.e., the hinge axes, which appear to be more
      flexible in substrate complexes. The flexibility of HIV-1 protease is likely
      optimized for the substrates' turnover, resulting in substrate complexes being
      dynamic. In contrast, in an inhibitor complex, the inhibitor should bind and lock
      down to inactivate the active site. Protease and ligands are not independent.
      Substrates are also more flexible than inhibitors and have the potential to meet
      the dynamic distributions that are inherent in the protease. This may suggest a
      rationale and guidelines for designing inhibitors that can better fit the
      ensemble of binding sites that are dynamically accessible to the protease.

PMID- 20816080
TI  - Detecting protein aggregates on untreated human tissue samples by atomic force
      microscopy recognition imaging.
AB  - We apply topography and recognition (TREC) imaging to the analysis of whole,
      untreated human tissue for what we believe to be the first time.
      Pseudoexfoliation syndrome (PEX), a well-known cause of irreversible blindness
      worldwide, is characterized by abnormal protein aggregation on the anterior lens
      capsule of the eye. However, the development of effective therapies has been
      hampered by a lack of detailed knowledge of the protein constituents in these
      pathological deposits and their distribution. Using both TREC and
      immunofluorescence, one of the proteins implicated in the PEX pathology--the
      apolipoprotein clusterin--was detected, and differences in its distribution
      pattern on the surface of untreated human lens capsule tissue in both PEX and
      normal control samples were investigated. Our study shows the potential of TREC
      imaging for the analysis of whole, untreated human tissue samples.

PMID- 20816081
TI  - Mechanics of microtubules: effects of protofilament orientation.
AB  - Microtubules are hollow cylindrical polymers of the protein tubulin that play a
      number of important dynamic and structural roles in eukaryotic cells. Both in
      vivo and in vitro microtubules can exist in several possible configurations,
      differing in the number of protofilaments, helical rise of tubulin dimers, and
      protofilament skew angle with respect to the main tube axis. Here, finite element
      modeling is applied to examine the mechanical response of several known
      microtubule types when subjected to radial deformation. The data presented here
      provide an important insight into microtubule stiffness and reveal that
      protofilament orientation does not affect radial stiffness. Rather, stiffness is
      primarily dependent on the effective Young's modulus of the polymerized material
      and the effective radius of the microtubule. These results are also directly
      correlated to atomic force microscopy nanoindentation measurements to allow a
      more detailed interpretation of previous experiments. When combined with
      experimental data that show a significant difference between microtubules
      stabilized with a slowly hydrolyzable GTP analog and microtubules stabilized with
      paclitaxel, the finite element data suggest that paclitaxel increases the overall
      radial flexibility of the microtubule wall.

PMID- 20816083
TI  - Ferrit(in)ing out new mechanisms in iron homeostasis.
AB  - Exquisite control of intestinal iron absorption prevents iron deficiency and
      toxic iron overload. Absorption is modulated by a circulating hormone, hepcidin,
      which inactivates the iron transporter ferroportin. In this issue of Cell
      Metabolism, Vanoaica and colleagues show that absorption is also regulated within
      the intestinal epithelium, through production of the iron-sequestering protein H
      ferritin.

PMID- 20816082
TI  - Probing structural transitions in the intrinsically disordered C-terminal domain
      of the measles virus nucleoprotein by vibrational spectroscopy of cyanylated
      cysteines.
AB  - Four single-cysteine variants of the intrinsically disordered C-terminal domain
      of the measles virus nucleoprotein (N(TAIL)) were cyanylated at cysteine and
      their infrared spectra in the C triple bond N stretching region were recorded
      both in the absence and in the presence of one of the physiological partners of
      N(TAIL), namely the C-terminal X domain (XD) of the viral phosphoprotein.
      Consistent with previous studies showing that XD triggers a disorder-to-order
      transition within N(TAIL), the C triple bond N stretching bands of the infrared
      probe were found to be significantly affected by XD, with this effect being
      position-dependent. When the cyanylated cysteine side chain is solvent-exposed
      throughout the structural transition, its changing linewidth reflects a local
      gain of structure. When the probe becomes partially buried due to binding, its
      frequency reports on the mean hydrophobicity of the microenvironment surrounding
      the labeled side chain of the bound form. The probe moiety is small compared to
      other common covalently attached spectroscopic probes, thereby minimizing
      possible steric hindrance/perturbation at the binding interface. These results
      show for the first time to our knowledge the suitability of site-specific
      cysteine mutagenesis followed by cyanylation and infrared spectroscopy to
      document structural transitions occurring within intrinsically disordered
      regions, with regions involved in binding and folding being identifiable at the
      residue level.

PMID- 20816084
TI  - Separating the good and evil of cardiac growth by CIB1 and calcineurin.
AB  - Ca(2+)-calcineurin-NFAT signaling plays a major role in promoting pathological
      cardiac hypertrophy. Heineke et al. (2010) show that CIB1 strongly enhances
      calcineurin activation and cardiac hypertrophy upon pathological stress, likely
      by functioning as a scaffold protein that exposes calcineurin to the L-Type
      Ca(2+) channel and the sarcolemma.

PMID- 20816085
TI  - A new role for cyclic phosphatidic acid as a PPARgamma antagonist.
AB  - A recent study in Molecular Cell (Tsukahara et al., 2010) identifies cyclic
      phosphatidic acid (CPA) as a naturally occurring PPARgamma antagonist that can be
      generated from lysophospholipids by signal-dependent activation of phospholipase
      D2. This endogenous CPA regulates PPARgamma functions required for adipogenesis,
      glucose homeostasis, and vascular wall biology.

PMID- 20816086
TI  - The long and short of fertility and longevity.
AB  - Does life span extension come with a reproductive trade-off? In a recent report
      published in Nature, Greer et al. (2010) show that in the nematode worm C.
      elegans, life span extension, as a consequence of deficiencies in histone
      methylation, requires an intact germline and ongoing fertility.

PMID- 20816087
TI  - Assembling complex I with ACAD9.
AB  - Acyl-Co dehydrogenase 9 (ACAD9) was thought to play a role in fatty acid
      oxidation. Nouws et al. (2010) reveal a novel and essential role for this enzyme
      in mitochondrial complex I assembly. A mutation in ACAD9 causes an isolated
      complex I deficiency in a subset of patients with mitochondrial disease.

PMID- 20816088
TI  - Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic
      lipoprotein export.
AB  - Recent genome-wide association studies (GWAS) have revealed strong association of
      hypercholesterolemia and myocardial infarction with SNPs on human chromosome
      1p13.3. This locus covers three genes: SORT1, CELSR2, and PSRC1. We demonstrate
      that sortilin, encoded by SORT1, is an intracellular sorting receptor for
      apolipoprotein (apo) B100. It interacts with apoB100 in the Golgi and facilitates
      the formation and hepatic export of apoB100-containing lipoproteins, thereby
      regulating plasma low-density lipoprotein (LDL) cholesterol. Absence of sortilin
      in gene-targeted mice reduces secretion of lipoproteins from the liver and
      ameliorates hypercholesterolemia and atherosclerotic lesion formation in LDL
      receptor-deficient animals. In contrast, sortilin overexpression stimulates
      hepatic release of lipoproteins and increases plasma LDL levels. Our data have
      uncovered a regulatory pathway in hepatic lipoprotein export and suggest a
      molecular explanation for the cardiovascular risk being associated with 1p13.3.

PMID- 20816089
TI  - Hepatic-specific disruption of SIRT6 in mice results in fatty liver formation due
      to enhanced glycolysis and triglyceride synthesis.
AB  - Under various conditions, mammals have the ability to maintain serum glucose
      concentration within a narrow range. SIRT1 plays an important role in regulating
      gluconeogenesis and fat metabolism; however, the underlying mechanisms remain
      elusive. Here, we show that SIRT1 forms a complex with FOXO3a and NRF1 on the
      SIRT6 promoter and positively regulates expression of SIRT6, which, in turn,
      negatively regulates glycolysis, triglyceride synthesis, and fat metabolism by
      deacetylating histone H3 lysine 9 in the promoter of many genes involved in these
      processes. Liver-specific deletion of SIRT6 in mice causes profound alterations
      in gene expression, leading to increased glycolysis, triglyceride synthesis,
      reduced beta oxidation, and fatty liver formation. Human fatty liver samples
      exhibited significantly lower levels of SIRT6 than did normal controls. Thus,
      SIRT6 plays a critical role in fat metabolism and may serve as a therapeutic
      target for treating fatty liver disease, the most common cause of liver
      dysfunction in humans.

PMID- 20816090
TI  - Interleukin-6 signaling in liver-parenchymal cells suppresses hepatic
      inflammation and improves systemic insulin action.
AB  - The contribution of interleukin (IL)-6 signaling in obesity-induced inflammation
      remains controversial. To specifically define the role of hepatic IL-6 signaling
      in insulin action and resistance, we have generated mice with hepatocyte-specific
      IL-6 receptor (IL-6R) alpha deficiency (IL-6Ralpha(L-KO) mice). These animals
      showed no alterations in body weight and fat content but exhibited a reduction in
      insulin sensitivity and glucose tolerance. Impaired glucose metabolism originated
      from attenuated insulin-stimulated glucose transport in skeletal muscle and fat.
      Surprisingly, hepatic IL-6Ralpha-disruption caused an exaggerated inflammatory
      response during euglycemic hyperinsulinemic clamp analysis, as revealed by
      increased expression of IL-6, TNF-alpha, and IL-10, as well as enhanced
      activation of inflammatory signaling such as phosphorylation of IkappaBalpha.
      Neutralization of TNF-alpha or ablation of Kupffer cells restored glucose
      tolerance in IL-6Ralpha(L-KO) mice. Thus, our results reveal an unexpected role
      for hepatic IL-6 signaling to limit hepatic inflammation and to protect from
      local and systemic insulin resistance.

PMID- 20816091
TI  - Insulin controls the spatial distribution of GLUT4 on the cell surface through
      regulation of its postfusion dispersal.
AB  - While the glucose transporter-4 (GLUT4) is fundamental to insulin-regulated
      glucose metabolism, its dynamic spatial organization in the plasma membrane (PM)
      is unclear. Here, using multicolor TIRF microscopy in transfected adipose cells,
      we demonstrate that insulin regulates not only the exocytosis of GLUT4 storage
      vesicles but also PM distribution of GLUT4 itself. In the basal state, domains
      (clusters) of GLUT4 molecules in PM are created by an exocytosis that retains
      GLUT4 at the fusion site. Surprisingly, when insulin induces a burst of GLUT4
      exocytosis, it does not merely accelerate this basal exocytosis but rather
      stimulates approximately 60-fold another mode of exocytosis that disperses GLUT4
      into PM. In contradistinction, internalization of most GLUT4, regardless of
      insulin, occurs from pre-existing clusters via the subsequent recruitment of
      clathrin. The data fit a new kinetic model that features multifunctional clusters
      as intermediates of exocytosis and endocytosis.

PMID- 20816093
TI  - Intestinal ferritin H is required for an accurate control of iron absorption.
AB  - To maintain appropriate body iron levels, iron absorption by the proximal
      duodenum is thought to be controlled by hepcidin, a polypeptide secreted by
      hepatocytes in response to high serum iron. Hepcidin limits basolateral iron
      efflux from the duodenal epithelium by binding and downregulating the intestinal
      iron exporter ferroportin. Here, we found that mice with an intestinal ferritin H
      gene deletion show increased body iron stores and transferrin saturation. As
      expected for iron-loaded animals, the ferritin H-deleted mice showed induced
      liver hepcidin mRNA levels and reduced duodenal expression of DMT1 and DcytB
      mRNA. In spite of these feedback controls, intestinal ferroportin protein and
      (59)Fe absorption were increased more than 2-fold in the deleted mice. Our
      results demonstrate that hepcidin-mediated regulation alone is insufficient to
      restrict iron absorption and that intestinal ferritin H is also required to limit
      iron efflux from intestinal cells.

PMID- 20816092
TI  - Insulin-like signaling determines survival during stress via posttranscriptional
      mechanisms in C. elegans.
AB  - The insulin-like signaling (ILS) pathway regulates metabolism and is known to
      modulate adult life span in C. elegans. Altered stress responses and resistance
      to a wide range of stressors are also associated with changes in ILS and
      contribute to enhanced longevity. The transcription factors DAF-16 and HSF-1 are
      key effectors of the longevity phenotype. We demonstrate that increased intrinsic
      thermotolerance, due to lower ILS, is not dependent on stress-induced
      transcriptional responses but instead requires active protein translation.
      Translation profiling experiments reveal genes that are posttranscriptionally
      regulated in response to altered ILS during heat shock in a DAF-16-dependent
      manner. Furthermore, several novel proteins are specifically required for ILS
      effects on thermotolerance. We propose that lowered ILS results in metabolic and
      physiological changes. These DAF-16-induced changes precondition a translational
      response under acute stress to modulate survival.

PMID- 20816096
TI  - Promoting the freedom to protect.

PMID- 20816094
TI  - Acyl-CoA dehydrogenase 9 is required for the biogenesis of oxidative
      phosphorylation complex I.
AB  - Acyl-CoA dehydrogenase 9 (ACAD9) is a recently identified member of the acyl-CoA
      dehydrogenase family. It closely resembles very long-chain acyl-CoA dehydrogenase
      (VLCAD), involved in mitochondrial beta oxidation of long-chain fatty acids.
      Contrary to its previously proposed involvement in fatty acid oxidation, we
      describe a role for ACAD9 in oxidative phosphorylation. ACAD9 binds complex I
      assembly factors NDUFAF1 and Ecsit and is specifically required for the assembly
      of complex I. Furthermore, ACAD9 mutations result in complex I deficiency and not
      in disturbed long-chain fatty acid oxidation. This strongly contrasts with its
      evolutionary ancestor VLCAD, which we show is not required for complex I assembly
      and clearly plays a role in fatty acid oxidation. Our results demonstrate that
      two closely related metabolic enzymes have diverged at the root of the vertebrate
      lineage to function in two separate mitochondrial metabolic pathways and have
      clinical implications for the diagnosis of complex I deficiency.

PMID- 20816095
TI  - Rescue of obesity-induced infertility in female mice due to a pituitary-specific
      knockout of the insulin receptor.
AB  - Obesity is associated with insulin resistance in metabolic tissues such as
      adipose, liver, and muscle, but it is unclear whether nonclassical target
      tissues, such as those of the reproductive axis, are also insulin resistant. To
      determine if the reproductive axis maintains insulin sensitivity in obesity in
      vivo, murine models of diet-induced obesity (DIO) with and without intact insulin
      signaling in pituitary gonadotrophs were created. Diet-induced obese wild-type
      female mice (WT DIO) were infertile and experienced a robust increase in
      luteinizing hormone (LH) after gonadotropin-releasing hormone (GnRH) or insulin
      stimulation. By contrast, both lean and obese mice with a pituitary-specific
      knockout of the insulin receptor (PitIRKO) exhibited reproductive competency,
      indicating that insulin signaling in the pituitary is required for the
      reproductive impairment seen in DIO and that the gonadotroph maintains insulin
      sensitivity in a setting of peripheral insulin resistance.

PMID- 20816098
TI  - Slate of candidates and new voting procedures.

PMID- 20816097
TI  - Shared cognition: reflecting, considering, deliberating.

PMID- 20816099
TI  - Award-winning clinical improvement/innovation posters: Sunday, March 14, to
      Thursday, March 18, 2010.

PMID- 20816100
TI  - Effectively conducting an advanced literature search.

PMID- 20816101
TI  - The development of a pressure ulcer risk-assessment scale for perioperative
      patients.
AB  - The high incidence of pressure ulcer development in patients in the perioperative
      setting indicates the need for improved risk assessment and the use of preventive
      measures. A clinical nurse specialist used Dever's Epidemiological Model as the
      theoretical framework to develop a perioperative pressure ulcer risk-assessment
      scale. The risk factors for the scale were based on findings from a review of the
      literature. The scale, along with a demographic questionnaire and an evaluation
      form, was distributed to 12 nurses and three anesthesiologists to obtain expert
      opinion to further the design of the scale. Twelve participants returned the
      forms. Only four of the participants had previous experience with a pressure
      ulcer risk-assessment scale. The results indicated that diabetes should be
      included as a risk factor category and that preexisting skin ulcerations,
      breakdowns, and conditions should be addressed within the scale. The participants
      unanimously agreed that moisture is an important factor to assess. Validation of
      each risk factor is essential to improve the reliability of the scale before its
      implementation.

PMID- 20816102
TI  - Reducing surgical site infections by bundling multiple risk reduction strategies
      and active surveillance.
AB  - Postoperative surgical site infections (SSIs) are serious health care-associated
      infections that contribute to higher rates of mortality. Methicillin-resistant
      Staphylococcus aureus (MRSA) is an increasingly common cause of SSIs. A quality
      improvement intervention was developed to identify surgical patients with nasal
      colonization of MRSA, treat them with mupirocin, and introduce a new preoperative
      skin antisepsis protocol using 2% chlorhexidine gluconate cloths. The total
      number of SSIs was reduced by 63%, and MRSA SSIs decreased by 78%. Preoperative
      MRSA screening and treatment and the preoperative skin antisepsis protocol were
      smoothly integrated into the facility workflow and well accepted by patients.
      This intervention saved two community hospitals an estimated $240,000.

PMID- 20816103
TI  - Perioperative care of the morbidly obese patient in the lithotomy position.
AB  - The lithotomy position is used daily in the OR to position patients for vaginal,
      rectal, and urologic procedures. Use of this position requires a careful nursing
      assessment to ensure that the patient can tolerate having his or her legs placed
      in the stirrups and to ensure that no pressure points exist for the duration of
      the surgery. Caring for a patient who is morbidly obese and who requires surgery
      in the lithotomy position can be especially challenging, and the possibility of
      injury to the patient or staff members should be considered. A case study
      involving the care of a patient who weighed almost 600 lb undergoing surgery in
      the lithotomy position demonstrates ways to provide safe care for this type of
      challenging patient.

PMID- 20816104
TI  - Measuring and improving ambulatory surgery patients' satisfaction.
AB  - The pressure on perioperative services to improve quality for health care
      consumers creates both challenges and opportunities. To make positive changes,
      many health care organizations contract with Press Ganey (PG), which processes an
      extensive database of more than 9.5 million surveys annually and provides
      benchmark reports to same-type organizations. To measure and improve ambulatory
      surgery patient satisfaction at one health care network in northeastern
      Pennsylvania, the nursing leaders in the ambulatory surgery center and OR
      undertook a quality improvement project focused on educating perioperative nurses
      on the use of PG reports. After we reviewed the PG reports and implemented
      changes with nursing staff members in perioperative areas, PG patient
      satisfaction scores improved regarding information about delays (4.1%) and center
      attractiveness (0.2%).

PMID- 20816105
TI  - Reducing the risks associated with loaner instrumentation and implants.
AB  - Surgical facilities borrow specialty surgical instrumentation and implants from
      vendors and other facilities to provide needed inventory to perform scheduled
      procedures without the burden of purchasing these items. Borrowing has many
      advantages, including reduced costs and the ability to expand services offered,
      but borrowed items must be handled and processed in a consistent way to ensure
      safe patient care. Instruments and implants must be received in time to be
      properly reprocessed by the borrowing facility. Lack of planning on the part of a
      hospital or vendor, lack of communication, lack of appropriate policies to guide
      the processing of items, increasingly complex instrumentation, and increasing
      workloads are factors that can contribute to lapses in processing requirements
      and, ultimately, risk to patients and staff members. Improving communication and
      policies and procedures can improve the quality and safety of loaner
      instrumentation and implant use.

PMID- 20816106
TI  - Using a Plan-Do-Study-Act cycle to introduce a new or service line.
AB  - In 2008, a multidisciplinary team at the Medical Center of Georgia, Macon, began
      a one-year Plan-Do-Study-Act (PDSA) cycle to implement a high-quality pediatric
      surgery service line. The PDSA team defined goals, objectives, and measurable
      performance metrics and then reviewed cases and aggregated data monthly to
      identify and improve clinical, process, instrument, and supply problems as well
      as patient transfer issues. The PDSA cycle led to improvements in team
      performance, communication, and patient transfer and decreased the number of
      problems associated with instruments, supplies, equipment, and surgeon tardiness.

PMID- 20816107
TI  - Interdisciplinary teamwork helps quality efforts reach new heights.

PMID- 20816108
TI  - Surgical smoke evacuation during laparoscopic surgery.

PMID- 20816109
TI  - Surgical sealant for preventing air leaks after pulmonary resections in patients
      with lung cancer.

PMID- 20816110
TI  - Clinical issues-September 2010.

PMID- 20816112
TI  - X-ray flip.

PMID- 20816113
TI  - Contribution of high plasma triglycerides and low high-density lipoprotein
      cholesterol to residual risk of coronary heart disease after establishment of low
      density lipoprotein cholesterol control.
AB  - To determine the relative contributions of triglycerides (TGs) and high-density
      lipoprotein (HDL) cholesterol in the residual risk of coronary heart disease
      (CHD) after the reduction of low-density lipoprotein (LDL) cholesterol to
      guideline-recommended levels, we conducted a hospital-based, case-control study
      with optimal matching in the strata of LDL cholesterol, gender, ethnicity, and
      age. The 170 cases and 175 controls were patients at Brigham and Women's Hospital
      (Boston, Massachusetts) from 2005 to 2008 who had an LDL cholesterol level <130
      mg/dl. The cases had incident CHD, and the controls had diagnoses unrelated to
      CHD. The 170 cases and 175 controls had a mean LDL cholesterol level of 73 and 87
      mg/dl, respectively. The association between TG and HDL cholesterol levels and
      CHD risk was assessed using conditional and unconditional logistic regression
      analysis. The models investigated accommodated the possibility of an interaction
      between lipid factors. The odds of CHD increased by approximately 20% per 23
      mg/dl increase in TGs and decreased by approximately 40% per 7.5-mg/dl decrease
      in HDL cholesterol. High TGs and low HDL cholesterol interacted synergistically
      to increase the odds ratio to 10 for the combined greatest TG (> or =190 mg/dl)
      and lowest HDL cholesterol quintiles (<30 mg/dl). High TG levels were more
      strongly associated with CHD when the HDL cholesterol was low than average or
      high; and low HDL cholesterol levels were more strongly associated with CHD when
      the TGs were high. TGs and HDL cholesterol were associated with CHD in patients
      with a LDL cholesterol level of < or =70 mg/dl, with a risk similar to, or
      greater than, those in the total group. In conclusion, high TG and low HDL
      cholesterol levels contribute strongly and synergistically to CHD when LDL
      cholesterol is well controlled. Thus, high TGs might have greater importance in
      patients with optimal rather than greater LDL cholesterol concentrations.

PMID- 20816114
TI  - Relation of elevated plasma renin activity at baseline to cardiac events in
      patients with angiographically proven coronary artery disease.
AB  - Plasma renin activity (PRA) is a measure of renin-angiotensin system activity and
      is associated with cardiovascular outcomes in patients with heart failure (HF).
      We conducted a prospective analysis to assess whether elevated baseline PRA is
      associated with cardiovascular outcomes in 1,165 patients with coronary artery
      disease (> or =70% stenosis on the coronary angiogram) enrolled in the
      Intermountain Heart Collaborative Study. The exclusion criteria included previous
      myocardial infarction (MI) or HF, ejection fraction < or =45%, and a discharge
      diagnosis of MI/beta-blocker treatment. Baseline PRA measurements were evaluated
      as risk categories (< or =0.50, 0.51 to 2.30, and >2.30 ng/ml/h) and as tertiles
      (< or =0.40, 0.41 to 1.90, and > or =1.90 ng/ml/h). Predefined cardiovascular
      outcomes were assessed for a minimum follow-up of 3 years (mean 6.4 +/- 3.2,
      maximum 14.6) using Cox regression analysis to adjust for the baseline
      characteristics. The mean patient age was 64.4 years; most patients were men
      (73.1%) and hypertensive (63.2%). Elevated baseline PRA (high vs low category;
      >2.30 vs < or =0.50 ng/ml/h) was associated with a significantly increased risk
      of 3-year cardiac morbidity/mortality (hazard ratio 1.96; p = 0.004), MI (hazard
      ratio 2.41; p = 0.02), HF hospitalization (hazard ratio 4.39; p = 0.03), and all
      cause death (hazard ratio 1.80; p = 0.01). Elevated baseline PRA was also
      associated with longer-term HF hospitalization (hazard ratio 2.12; p = 0.004) and
      all-cause death (hazard ratio 1.56; p = 0.002). Similar results were observed for
      the PRA tertiles. The association of PRA with outcomes was observed after
      correction for hypertension, hyperlipidemia, diabetes, a family history of
      cardiovascular events, smoking, renal failure, and the use of statins. In
      conclusion, elevated baseline PRA is associated with cardiac morbidity and
      mortality in patients with coronary artery disease but normal left ventricular
      function and no previous MI or HF.

PMID- 20816115
TI  - Usefulness of primary angioplasty in nonagenarians with acute myocardial
      infarction.
AB  - The optimal reperfusion strategy in very elderly patients with ST-segment
      elevation myocardial infarction is still a subject of debate. The aim of this
      multicenter study was to determine the medium-term outcomes of nonagenarians
      after primary percutaneous intervention for ST-segment elevation myocardial
      infarction. A systematic review of the databases of 7 Italian centers showed that
      these had performed 5,023 primary angioplasties over the previous 5 years, 100 of
      which (2%) involved patients > or =90 years old. Thirty-five subjects were in
      Killip class III or IV at time of presentation, 78 had multivessel coronary
      artery disease, and mean ejection fraction was 0.40 +/- 0.12%. In-hospital
      mortality was 19% and was significantly higher in patients with shock (58% vs
      10%, p <0.001). Survival rate after 6 months was 68%: 16% in those with Killip
      class IV at admission and 81% in the remaining patients (p <0.001). Cox
      regression analysis identified 3 independent predictors of 6-month mortality:
      cardiogenic shock at presentation (hazard ratio [HR] 10.82, 95% confidence
      interval [CI] 4.51 to 25.93, p <0.001), Thrombolysis In Myocardial Infarction
      myocardial flow after percutaneous coronary intervention (HR 0.19, 95% CI 0.07 to
      0.50, p = 0.001), and abciximab administration (HR 0.32, 95% CI 0.13 to 0.78, p =
      0.01). In conclusion, the results of this multicenter study suggest that selected
      nonagenarians with acute myocardial infarction benefit from successful primary
      angioplasty. The treatment does not affect the poor prognosis of patients
      presenting with cardiogenic shock, but the administration of abciximab seems to
      have a positive effect on 6-month mortality.

PMID- 20816116
TI  - Effect of coronary target lesion revascularization on late cardiac events after
      insertion of sirolimus-eluting or bare metal stents.
AB  - Restenosis is associated with acute myocardial infarction (MI) either at
      presentation or related to complications of target lesion revascularization
      (TLR). The cumulative late effect of TLR after drug-eluting or bare metal stent
      placement on cardiac death or MI is uncertain. Of the 1,057 patients with one
      native coronary lesion randomized to a sirolimus-eluting stent or bare metal
      stent in the Sirolimus-Eluting Stent in De Novo Native Coronary Lesions (SIRIUS)
      trial, the 983 who survived free of MI for the first 30 days were evaluated for
      the primary outcome of cardiac death or MI for 5 years. Patients with events
      occurring at or after TLR were assigned to TLR group. Cox proportional hazards
      regression analysis with TLR as a time-dependent variable and adjustment for
      baseline clinical and demographic covariates was used to assess the independent
      effect of TLR on the primary outcome. TLR occurred in 160 patients (16.3%) and
      was an independent predictor of the primary end point (hazard ratio 2.8, 95%
      confidence interval 1.7 to 4.5). This association was significant for sirolimus
      eluting stents and bare metal stents. TLR was also associated with an increased
      risk of subsequent stent thrombosis and nontarget vessel revascularization.
      Intracoronary brachytherapy in the TLR group was associated with an increased
      risk of cardiac death or MI. In conclusion, restenosis requiring TLR was
      associated with an increased risk of cardiac death or MI occurring at TLR and
      during the subsequent 5 years.

PMID- 20816117
TI  - Long-term prognostic value of cardiac troponin I and T versus creatine kinase-MB
      mass after cardiac surgery in low-risk patients with stable symptoms.
AB  - The long-term prognostic value of elevated cardiac biomarkers after elective
      cardiac surgery is not clear. The recent guidelines for diagnosing perioperative
      infarcts have advocated the use of similar thresholds for creatine kinase-MB (CK
      MB) mass and the cardiac troponins. However, few previous data are available
      comparing these biomarkers after cardiac surgery, and it is not clear whether
      postoperative elevations of the troponins can be treated the same as elevations
      of CK-MB. We sought to compare the prognostic value of the cardiac troponins
      versus the CK-MB mass after elective cardiac surgery in low-risk patients with
      stable symptoms. A total of 204 consecutive patients undergoing cardiac surgery
      were included in the final analysis. Blood samples were drawn just before and 1
      to 3 and 4 to 8 hours after the procedure, and every morning for 3 days
      thereafter. Patients with elevated baseline values were excluded. Using a cutoff
      value of 5 times the reference, patients with high and low values (controls) of
      CK-MB mass, cardiac troponin T (cTnT) and cardiac troponin I (cTnI) were
      compared. The median follow-up time was 92 months. None developed new Q-waves on
      the electrocardiogram. The incidence of the composite end point of all-cause
      mortality, readmission for acute coronary syndrome, and target vessel
      revascularization in the high CK-MB group was 41.2% compared to 21.8% in the
      controls (p = 0.004). The corresponding values for cTnT were 33.3% and 20.4% (p =
      0.075) and for cTnI were 27.0% and 34.6% (p = 0.237). The p value in the isolated
      coronary artery bypass grafting subgroup (n = 156) was p = 0.043 for CK-MB, p =
      0.137 for cTnT, and p = 0.795 for cTnI. High CK-MB (p = 0.001), ejection fraction
      (p = 0.002), and body mass index (p = 0.010) were the only variables
      independently related to reduced event-free survival. No such relation was found
      for high cTnT and cTnI. In conclusion, CK-MB was superior to the cardiac
      troponins (values > or =5 times the reference) in predicting long-term event-free
      survival after elective cardiac surgery in low-risk patients with stable symptoms
      undergoing coronary artery bypass grafting and/or valve surgery.

PMID- 20816118
TI  - Efficacy and safety of adding fenofibrate 160 mg in high-risk patients with mixed
      hyperlipidemia not controlled by pravastatin 40 mg monotherapy.
AB  - Patients with mixed hyperlipidemia and at high risk of coronary heart disease may
      not achieve recommended low-density lipoprotein (LDL) and non-high-density
      lipoprotein (non-HDL) cholesterol goals on statin monotherapy. This study was
      designed to evaluate the efficacy and safety of a fenofibrate 160 mg/pravastatin
      40 mg fixed-dose combination therapy in high-risk patients not at their LDL
      cholesterol goal on pravastatin 40 mg. In this 12-week, multicenter, randomized,
      double-blind, double-dummy, parallel-group study, after a run-in on pravastatin
      40 mg, 248 patients were randomly assigned to fenofibrate/pravastatin combination
      therapy or to pravastatin monotherapy. Combination therapy produced significantly
      greater complementary decreases in non-HDL cholesterol (primary end point) than
      pravastatin monotherapy (-14.1% vs -6.1%, p = 0.002). Significantly greater
      improvements were also observed in LDL cholesterol (-11.7% vs -5.9%, p = 0.019),
      HDL cholesterol (+6.5% vs +2.3%, p = 0.009), triglycerides (-22.6% vs -2.0%, p =
      0.006), and apolipoprotein B (-12.6% vs -3.8%, p <0.0001). Significantly more
      patients receiving the fenofibrate/pravastatin combination therapy than
      pravastatin alone achieved the LDL cholesterol (<100 mg/dl) and non-HDL
      cholesterol (<130 mg/dl) goals (p <0.01). Combination therapy was generally well
      tolerated with incidences of clinical and laboratory adverse experiences similar
      between the 2 groups. In conclusion, the fenofibrate 160 mg/pravastatin 40 mg
      fixed-dose combination therapy significantly improved the global atherogenic
      lipid profile in high-risk patients with mixed hyperlipidemia not controlled by
      pravastatin 40 mg monotherapy.

PMID- 20816119
TI  - Relation of serum phosphorus levels to carotid intima-media thickness in
      asymptomatic young adults (from the Bogalusa Heart Study).
AB  - Increased serum phosphorus has been associated with increased mortality from
      cardiovascular (CV) disease. However, information is scant regarding the
      influence of serum phosphorus within the normal range on vascular risk in
      subclinical atherosclerosis in asymptomatic young adults. Serum phosphorus and
      other CV risk factor variables were measured in 856 white and 354 black subjects
      without known CV disease or renal disease. Carotid intima-media thickness (IMT)
      was measured by B-mode ultrasonography. Significant race and gender differences
      were noted for serum phosphorus (blacks > whites) and carotid IMT (black women >
      white women; men > women). In bivariate analyses, serum phosphorus was correlated
      with carotid IMT (p <0.001), and smokers showed higher phosphorus levels than
      nonsmokers (p = 0.008). In multivariate regression analyses, carotid IMT was
      significantly associated with serum phosphorus (regression coefficient beta =
      0.028, p <0.001) and smoking (beta = 0.032, p <0.001), adjusting for other CV
      risk factors and estimated glomerular filtration rate. In addition, a significant
      interaction effect of cigarette smoking and serum phosphorus on carotid IMT was
      noted, with a greater increasing trend of carotid IMT with phosphorus in smokers
      than in nonsmokers (p = 0.019 for interaction). In conclusion, serum phosphorus
      within the normal range is an important correlate of carotid IMT in asymptomatic
      young adults, with smoking potentiating this adverse association.

PMID- 20816120
TI  - Role of vitamin D in cardiovascular health.
AB  - Observational studies strongly associate vitamin D deficiency with a variety of
      cardiovascular diseases beyond defects in bone and calcium metabolism. Vitamin D
      has multiple mechanisms that potentially may affect cardiovascular health.
      Because vitamin D deficiency is common, therapies directed at the replacement of
      vitamin D may be beneficial. To date however, studies evaluating vitamin D
      supplementation are few and have not consistently shown benefit. It is possible
      that the lack of benefit in these studies may have arisen from suboptimal levels
      of vitamin D supplementation or other unknown factors. Nevertheless, the growing
      body of observational data and consistent findings of relatively high rates of
      low vitamin D serum levels warrant further well-designed studies to investigate
      the relation between vitamin D and cardiovascular health. In conclusion, vitamin
      D is now recognized as important for cardiovascular health and its deficiency as
      a potential risk factor for several cardiovascular disease processes.

PMID- 20816121
TI  - Relation of right ventricular pacing site to left ventricular mechanical
      synchrony.
AB  - Transvenous pacing leads are regularly placed in the right ventricular (RV) apex.
      Pediatric patients can develop myopathic changes after long-term RV apical
      pacing. Left ventricular (LV) mechanical dyssynchrony, estimated with
      echocardiography, may explain the acute decrease in LV function and long-term
      histopathologic changes. Ts-4w is an established echocardiographic measurement of
      LV synchrony, using tissue Doppler imaging (TDI). The purpose of this study was
      to determine whether TDI could identify acute changes in LV synchrony during
      pacing from different RV sites. We prospectively measured Ts-4w and Doppler
      derived cardiac output after 5 minutes of pacing in 19 subjects undergoing
      catheter ablation. Each subject underwent pacing at 4 sites in random order: high
      right atrium, high RV septum (septal), RV outflow tract, and RV apex. Ts-4w was
      measured during sinus rhythm and each pacing protocol, with a value >65 ms
      defining mechanical dyssynchrony. Ts-4w during high right atrial (32.6 +/- 17.6
      ms) and septal (28.9 +/- 10.9 ms) pacing were not different from sinus rhythm
      (39.5 +/- 15.5 ms). RV apex (85.7 +/- 18.4 ms) and RV outflow tract (84.2 +/-
      20.4 ms) pacing induced mechanical dyssynchrony (p <0.0001). In conclusion, TDI
      demonstrated significant differences in LV synchrony related to pacing site. Ts
      4w may be useful to determine ideal lead placement because it correlates with
      acutely improved hemodynamics.

PMID- 20816122
TI  - Effect of amlodipine + candesartan on cardiovascular events in hypertensive
      patients with coronary artery disease (from The Heart Institute of Japan
      Candesartan Randomized Trial for Evaluation in Coronary Artery Disease [HIJ
      CREATE] Study).
AB  - Combination therapy with calcium channel blockers and angiotensin II receptor
      blockers is recommended as one of the effective therapies for hypertension.
      However, it remains unclear whether this combination reduces major adverse
      cardiovascular events (MACEs) in patients with hypertension with coronary artery
      disease (CAD). The purpose of the present study was to examine the effects of
      amlodipine plus candesartan on MACEs in patients with hypertension with CAD. The
      study population was drawn from The Heart Institute of Japan Candesartan
      Randomized Trial for Evaluation in Coronary Artery Disease (HIJ-CREATE), which
      was a multicenter, prospective, randomized controlled trial including 2,049
      patients with hypertension with angiographically documented CAD. Subgroup
      analysis was performed in patients treated with amlodipine at baseline (n = 388).
      The median follow-up period was 4.3 years. Treatment using amlodipine plus
      candesartan reduced the risk for MACEs by 39% (p = 0.015) compared to that using
      amlodipine without angiotensin II receptor blockers. Among the individual events
      constituting MACEs, the incidence of unstable angina pectoris requiring
      hospitalization was significantly lower, by 52% (p = 0.007). In conclusion,
      amlodipine plus candesartan demonstrated a more favorable effect on reducing
      cardiovascular events in patients with hypertension with CAD compared to
      amlodipine-based therapy without candesartan.

PMID- 20816123
TI  - Effectiveness of lowering blood pressure to prevent stroke versus to prevent
      coronary events.
AB  - The concept of the J-curve effect has been around for a long time and is a
      subject of contention among various investigators. The J-curve effect describes
      an inverse relation between low blood pressure (BP) and cardiovascular
      complications. Because the coronary arteries are perfused during diastole, this
      effect is seen mostly with low diastolic BP in the range of 70 to 80 mm Hg,
      depending on preexisting coronary artery disease, hypertension, or left
      ventricular hypertrophy. Although national and international guidelines recommend
      aggressive BP control to <140/90 mm Hg for uncomplicated hypertension or <130/80
      mm Hg for hypertension associated with coronary artery disease, diabetes, or
      chronic kidney disease, recent large clinical outcomes trials have observed a J
      curve effect between diastolic BP <80 mm Hg as well as systolic BP <130 mm Hg and
      have cast some doubt regarding the aggressive BP treatment, or "the lower the
      better," concept. Other recent studies have shown no benefit with respect to
      cardiovascular complications between aggressive and less aggressive BP control.
      In contrast to cardiovascular complications, no J-curve effect has been noted for
      strokes. A Medline search of English-language reports published from 1992 to 2010
      regarding this topic was conducted, and 11 reports were selected and are
      discussed in this brief review, together with collateral published research. In
      conclusion, most of the reviewed publications suggest a J-curve effect with low
      diastolic and systolic BP for cardiovascular disease complications but not stroke
      complications.

PMID- 20816124
TI  - Comparison of usefulness of each of five predictors of mortality and urgent
      transplantation in patients with advanced heart failure.
AB  - B-type natriuretic peptide (BNP), peak oxygen consumption (VO(2)), blood urea
      nitrogen (BUN), systolic blood pressure (SBP), and pulmonary capillary wedge
      pressure are all established predictors of mortality or urgent transplantation in
      patients with advanced heart failure (HF). However, their comparative predictive
      ability in estimating prognosis has not been well studied. We analyzed 1,215
      patients with advanced systolic HF referred to a university center from 1999 to
      2009. BUN, BNP, VO(2), SBP, and pulmonary capillary wedge pressure were measured
      as a part of the initial evaluation. The patients were divided into groups
      according to the best cutoffs for predicting both 1- and 2-year mortality from
      the analysis of the receiver operating characteristic curves (BNP > or =579
      pg/ml, peak VO(2) <14 ml/kg/min, BUN > or =53 mg/dl, SBP <118 mm Hg, and
      pulmonary capillary wedge pressure > or =21 mm Hg). During a 2-year follow-up,
      234 patients (19%) died, and 208 (17%) required urgent transplantation. BNP (odds
      ratio 4.3, 95% confidence interval 3.3 to 5.5) and peak VO(2) (odds ratio 4.5,
      95% confidence interval 2.6 to 7.8) were the strongest predictors for death or
      urgent transplantation. On multivariate analyses, BNP and peak VO(2) were the
      strongest predictors for both death or urgent transplantation and all-cause
      mortality. The c-statistic was 0.756 for BNP, 0.701 for VO(2), 0.659 for BUN,
      0.638 for SBP, and 0.650 for pulmonary capillary wedge pressure. In conclusion,
      of the 5 established predictors of outcomes in advanced HF, BNP was the most
      robust discriminator of risk and thus could be useful, along with other more
      traditional prognostic variables, in patient counseling regarding prognosis and
      determining the timing for heart transplantation.

PMID- 20816126
TI  - Usefulness of real-time three-dimensional echocardiography to identify right
      ventricular dysfunction in patients with congenital heart disease.
AB  - Because right ventricular (RV) dysfunction predicts a poor outcome in patients
      with congenital heart disease (CHD), regular monitoring of RV function is
      indicated. To date, cardiac magnetic resonance (CMR) imaging has been the
      reference method. A more practical, more accessible, and accurate tool would be
      preferred. We defined normality regarding RV systolic function using healthy
      controls and tested the ability of real-time 3-dimensional echocardiographic
      (RT3DE) findings to identify patients with CHD with RV dysfunction. The cutoff
      values for the RV volumes and ejection fraction (EF) were derived from the CMR
      imaging findings from 41 healthy controls (mean age 27 +/- 8 years, 56% men). In
      100 patients with varying CHDs (mean age 27 +/- 11 years, 65% men), both RT3DE
      data sets (iE33) and short-axis CMR imaging (1.5 T) were obtained within 2 hours.
      The RT3DE and CMR RV volumes and EF were calculated using commercially available
      software. Receiver operating characteristic curves were created to obtain the
      sensitivity and specificity of the RT3DE data to identify RV dysfunction.
      Applying the cutoff values derived from the healthy controls using the CMR data
      of patients with CHD, we identified 23 patients with an enlarged indexed end
      diastolic volume, 29 patients with an enlarged indexed end-systolic volume, and
      21 patients with an impaired RVEF. The best cutoff values predicting RV
      dysfunction using the RT3DE findings were identified (indexed end-diastolic
      volume >105 ml/m(2), indexed end-systolic volume >54 ml/m(2), and EF <43%). The
      RT3DE findings revealed 23 patients with impaired RVEF, with 95% sensitivity, 89%
      specificity, and a negative predictive value of 99%. In conclusion, real-time 3
      dimensional echocardiography is a very sensitive tool to identify RV dysfunction
      in patients with CHD and could be applied clinically to rule out RV dysfunction
      or to indicate additional quantitative analysis of RV function.

PMID- 20816125
TI  - Serial changes in left ventricular shape following early mitral valve repair.
AB  - Mitral valve (MV) repair has become the preferred treatment for mitral
      regurgitation associated with degenerative MV disease. Although the functional
      benefits of early MV repair are known, the associated alterations in left
      ventricular (LV) shape have not been studied. The aim of this study was to
      evaluate serial changes in LV performance and 3-dimensional (3D) shape after MV
      repair using a new analytic technique. Fifty patients (mean age 59 +/- 12 years)
      with severe asymptomatic mitral regurgitation and ejection fractions >55% who
      underwent MV repair were enrolled. Transthoracic real-time 3D echocardiography
      was performed the day before and 6 and 12 months after MV repair. An age-matched
      control group of 50 normal subjects was studied for comparison. Endocardial
      surfaces were extracted to compute 3D shape indexes of sphericity and conicity,
      which were compared in patients between different time points and versus the
      normal group. Postoperatively, LV volumes were decreased compared to presurgical
      values. Ejection fractions were slightly decreased 6 months after surgery but had
      restored by 12 months. These changes were associated with modifications in end
      diastolic LV shape: before surgery, compared to normal controls, sphericity was
      augmented and conicity was decreased; at 6 months, these shape changes were
      reversed, with no further improvements at 12 months. In conclusion, patients with
      asymptomatic mitral regurgitation and preserved LV function already exhibit
      changes in LV shape. Early MV repair leads to near normal morphology after
      surgery, indicating the benefits of this procedure. Real-time 3D echocardiography
      and novel 3D shape analysis allow detailed serial examination of the complex
      relation between LV performance and shape.

PMID- 20816127
TI  - Vascular function in children with repaired tetralogy of Fallot.
AB  - We compared the endothelial function and vascular wall characteristics of 11
      children with tetralogy of Fallot (TOF) (age 13 +/- 3 years) with the
      characteristics of 17 age-matched peers (12 +/- 2 years). Echocardiographic
      Doppler measurements were performed under standardized conditions to assess (1)
      the carotid and femoral artery diameter and intima-media thickness, (2) brachial
      artery endothelial function using flow-mediated dilation, and (3) central and
      peripheral compliance using pulsewave velocity. In addition, the physical
      activity level was assessed using a validated questionnaire. We found that the
      physical activity level of the children with TOF was lower than that of the
      controls, but the difference did not reach statistical significance (4.5 vs 5.9
      h/wk, p = 0.087). A significantly larger femoral artery intima-media thickness
      was observed in those with TOF, and the carotid and brachial artery diameter and
      intima-media thickness were comparable between groups. The children with TOF
      demonstrated a significantly lower brachial artery flow-mediated dilation than
      that of the controls. The central and peripheral compliance did not differ
      between the 2 groups. In conclusion, children with TOF demonstrated an impaired
      brachial artery endothelial function and increased intima-media thickness of the
      femoral artery compared to their healthy peers. In conclusion, our findings have,
      therefore, indicated that children with TOF, already at a young age, have changes
      in vascular function and structure.

PMID- 20816128
TI  - Effect of mirthful laughter on vascular function.
AB  - In contrast to the well-established scientific evidence linking negative
      emotional states (e.g., depression, anxiety, or anger) to increased risk for
      cardiovascular disease, much less is known about the association between positive
      emotional states (e.g., laughter, happiness) and cardiovascular health. We
      determined the effects of mirthful laughter, elicited by watching comic movies,
      on endothelial function and central artery compliance. Seventeen apparently
      healthy adults (23 to 42 years of age) watched 30 minutes of a comedy or a
      documentary (control) on separate days (crossover design). Heart rate and blood
      pressure increased significantly while watching the comedy, whereas no such
      changes were seen while watching the documentary. Ischemia-induced brachial
      artery flow-mediated vasodilation (by B-mode ultrasound imaging) increased
      significantly after watching the comedy (17%) and decreased with watching the
      documentary (-15%). Carotid arterial compliance (by simultaneous application of
      ultrasound imaging and applanation tonometry) increased (10%) significantly
      immediately after watching the comedy and returned to baseline 24 hours after the
      watching, whereas it did not change significantly throughout the documentary
      condition. Comedy-induced changes in arterial compliance were significantly
      associated with baseline flow-mediated dilation (r = 0.63). These results suggest
      that mirthful laughter elicited by comic movies induces beneficial impact on
      vascular function.

PMID- 20816129
TI  - Influence of left ventricular dysfunction (diastolic versus systolic) on long
      term prognosis in patients with versus without diabetes mellitus having elective
      peripheral arterial surgery.
AB  - Diabetes mellitus (DM) and left ventricular dysfunction (LVD) are often
      coexistent and invariably associated with increased mortality. Data on long-term
      prognosis of "isolated" diastolic LVD in diabetics are lacking; therefore, we
      evaluated these prognostic implications in patients with peripheral arterial
      disease (PAD) and DM. Using echocardiography, 1321 patients were screened for
      diastolic, systolic (ejection fraction <50%) or combined LVD. Diastolic LVD was
      diagnosed based on the ratio of early rapid filling to late filling due to atrial
      contraction, pulmonary vein flow, and deceleration time. Patients using glucose
      lowering drugs or insulin or with a fasting glucose level >6.1 mmol/L were
      diagnosed with DM. The primary end point was occurrence of cardiovascular death
      during a mean follow-up of 2.5 +/- 1.9 years. In the total population, DM was
      diagnosed in 518 patients (39%), and diastolic, systolic, or combined LVD was
      present in 356 patients (27%), 102 patients (8%), or 156 patients (12%),
      respectively. In diabetic patients, diastolic and systolic LVDs were associated
      with increased cardiovascular mortality (hazard ratio 1.8, 95% confidence
      interval 1.03 to 3.03; hazard ratio 3.1, 95% confidence interval 1.46 to 6.38).
      In nondiabetic patients, the same association between diastolic or systolic LVD
      and outcome was observed (hazard ratio 2.2, 95% confidence interval 1.30 to 3.74;
      hazard ratio 3.9, 95% confidence interval 2.00 to 7.52). Combined systolic and
      diastolic LVD had the worst prognosis. In conclusion, diabetic patients with PAD
      have an increased prevalence of isolated systolic and combined LVD. In patients
      with PAD the presence of isolated diastolic, systolic, or combined LVD was
      independently and equally associated with increased cardiovascular mortality,
      irrespective of the concomitant presence of DM.

PMID- 20816130
TI  - Usefulness of N-terminal pro-brain natriuretic peptide to predict postoperative
      cardiac complications and long-term mortality after emergency lower limb
      orthopedic surgery.
AB  - After emergency orthopedic-geriatric surgery, cardiac complications are an
      important cause of morbidity and mortality. The utility of N-terminal pro-brain
      natriuretic peptide (NT-pro-BNP) for the prediction of cardiac complications and
      mortality was evaluated. NT-pro-BNP was tested pre- and postoperatively in 89
      patients >60 years of age. They were followed for 2 years for cardiac
      complications (defined as acute myocardial infarction, congestive cardiac
      failure, atrial fibrillation or major arrhythmia) or death. Receiver operating
      characteristic curves were constructed to determine the optimal discriminatory
      level for cardiac events and death using NT-pro-BNP. Twenty-three patients
      (25.8%) sustained an in-hospital postoperative cardiac complication. Total all
      cause mortality was 3 of 89 (3.4%) in hospital, 21 of 89 (23.6%) at 1 year, and
      27 of 89 (30.3%) at 2 years. Median preoperative and postoperative NT-pro-BNP
      levels were higher in patients who had an in-hospital cardiac event compared to
      those without (387 vs 1,969 pg/ml, p <0.001; and 676 vs 7,052 pg/ml, p <0.001
      respectively). The optimal discriminatory level for preoperative NT-pro-BNP was
      842 pg/ml and that for postoperative NT-pro-BNP was 1,401 pg/ml for the
      prediction of in-hospital cardiac events and 1- and 2-year mortality.
      Preoperative NT-pro-BNP >/=842 pg/ml (odds ratio 11.6, 95% confidence interval
      2.1 to 65.0, p = 0.005) was an independent predictor of in-hospital cardiac
      complications using multivariate analysis and pre- and postoperative NT-pro-BNP
      levels were independent predictors of 2-year cardiovascular events. Patients who
      had preoperative NT-pro-BNP >/=842 pg/ml or postoperative NT-pro-BNP >/=1,401
      pg/ml had significantly worse survival using log-rank testing (p <0.001) and
      these variables independently predicted 2-year mortality. In conclusion, increase
      pre- and postoperative NT-pro-BNP levels are independent predictors of in
      hospital cardiac events and 1- and 2-year mortality in older patients undergoing
      emergency orthopedic surgery.

PMID- 20816131
TI  - AJC Editor's consensus: Selective and nonselective nonsteroidal anti-inflammatory
      drugs and cardiovascular risk.

PMID- 20816132
TI  - Analysis of the left atrial appendage by three-dimensional transesophageal
      echocardiography.
AB  - This study was designed to determine the ability and reliability of 3-dimensional
      (3D) transesophageal echocardiography (TEE) to assess the geometry and size of
      the left atrial appendage (LAA). Three-dimensional TEE may allow more accurate
      assessment of, and provide additional information on, LAA morphology compared to
      2-dimensional TEE. Validation studies for LAA morphology data derived from 3D TEE
      were performed using 10 isolated porcine LAA specimens. Of 107 enrolled patients,
      55 patients were in sinus rhythm (normal sinus rhythm), in whom 3D
      transesophageal echocardiographic images were obtained from full-volume mode
      imaging, and in 52 patients with atrial fibrillation, zoom-mode imaging was used.
      LAA orifice area, depth, and volume and the number of LAA lobes were assessed on
      reconstructed 3D imaging. Left atrial volume was calculated using 2-dimensional
      echocardiographic imaging. In experimental studies, excellent correlations (r
      >0.90, p <0.001) between the measurements by full-volume or zoom-mode imaging and
      reference data were observed in all parameters. The mean LAA orifice long
      diameter was 29.7 +/- 7.4 mm, the mean short diameter was 20.6 +/- 5.9 mm, the
      mean orifice area was 5.1 +/- 2.5 cm(2), the mean LAA depth was 38.5 +/- 8.2 mm,
      and the mean volume was 9.2 +/- 5.6 ml. The most frequent number of LAA lobes was
      2 (n = 52), followed by 3 (n = 28), 1 (n = 18), and 4 (n = 3). Left atrial volume
      was weakly correlated with LAA orifice long diameter (r = 0.33, p = 0.001), short
      diameter (r = 0.40, p <0.001), area (r = 0.39, p <0.001), LAA depth (r = 0.21, p
      = 0.03), and volume (r = 0.36, p = 0.001). In conclusion, 3D TEE is a reliable
      modality to evaluate LAA geometry and provides detailed information to quantify
      varied LAA characteristics.

PMID- 20816134
TI  - Is the present therapy for coronary artery disease the radical mastectomy of the
      twenty-first century?

PMID- 20816133
TI  - Cardiac and metabolic effects of anabolic-androgenic steroid abuse on lipids,
      blood pressure, left ventricular dimensions, and rhythm.
AB  - Recent surveys and reports suggest that many athletes and bodybuilders abuse
      anabolic-androgenic steroids (AAS). However, scientific data on the cardiac and
      metabolic complications of AAS abuse are divergent and often conflicting. A total
      of 49 studies describing 1,467 athletes were reviewed to investigate the
      cardiovascular effects of the abuse of AAS. Although studies were typically small
      and retrospective, some associated AAS abuse with unfavorable effects. Otherwise
      healthy young athletes abusing AAS may show elevated levels of low-density
      lipoprotein and low levels of high-density lipoprotein. Although data are
      conflicting, AAS have also been linked with elevated systolic and diastolic blood
      pressure and with left ventricular hypertrophy that may persist after AAS
      cessation. Finally, in small case studies, AAS abuse has been linked with acute
      myocardial infarction and fatal ventricular arrhythmias. In conclusion,
      recognition of these adverse effects may improve the education of athletes and
      increase vigilance when evaluating young athletes with cardiovascular
      abnormalities.

PMID- 20816135
TI  - Should statin therapy be allocated on the basis of global risk or on the basis of
      randomized trial evidence?
AB  - Current clinical guidelines recommend the use of a global risk assessment tool,
      such as those pioneered by the Framingham Heart Study, to determine eligibility
      for statin therapy in patients with absolute risk levels greater than a certain
      threshold. In support of this approach, several randomized trials have reported
      that patients with high absolute risk clearly benefit from statin therapy.
      Therefore, the guideline recommendations would seem intuitive and effective,
      albeit on the core assumption that the mortality and morbidity benefits
      associated with statin therapy would be greatest in those with high predicted
      absolute risk. However, if this assumption is incorrect, using predicted absolute
      risk to guide statin therapy could easily result in underuse in some groups and
      overuse in others. Herein, the authors question the utility of global risk
      assessment strategies based on the Framingham risk score for guiding statin
      therapy in light of current data that have become available from more recent and
      robust prospective randomized clinical trials since the publication of the
      National Cholesterol Education Program Adult Treatment Panel III guidelines.
      Moreover, the Adult Treatment Panel III guidelines do not support treatment of
      some patients who may benefit from statin therapy. In conclusion, the authors
      propose an alternative approach for incorporating more recent randomized trial
      data into future statin allocation algorithms and treatment guidelines.

PMID- 20816136
TI  - Heart rate variability and longevity.

PMID- 20816137
TI  - High heart rate variability, marker of healthy longevity.

PMID- 20816138
TI  - Foreword.

PMID- 20816140
TI  - The role of surgery in cancer prevention.

PMID- 20816141
TI  - Discussion: 'Scheduling the first prenatal visit' by Nettleman et al.
AB  - In the roundtable that follows, clinicians discuss a study published in this
      issue of the Journal in light of its methodology, relevance to practice, and
      implications for future research. Article discussed: Nettleman MD, Brewer J,
      Stafford M. Scheduling the first prenatal visit: office-based delays. Am J Obstet
      Gynecol 2010;203:207.e1-3.

PMID- 20816142
TI  - Squamous cell carcinoma arising from a localized vulval lesion of Hailey-Hailey
      disease after tacrolimus therapy.
AB  - Hailey-Hailey disease (HHD) is a rare, autosomal dominant intraepidermal
      blistering disorder characterized by recurrent vesicles and erosions affecting
      mostly the intertriginous areas. We report a case of HHD affecting exclusively
      the vulva from which an invasive squamous cell carcinoma developed after
      tacrolimus therapy.

PMID- 20816143
TI  - Changes.

PMID- 20816144
TI  - Using birth certificate data to determine medically indicated induction rates.

PMID- 20816145
TI  - Scheduling the first prenatal visit: a missed opportunity.

PMID- 20816146
TI  - Failure of 17-hydroxyprogesterone to reduce neonatal morbidity or prolong triplet
      pregnancy: a double-blind, randomized clinical trial.
AB  - OBJECTIVE: To test whether 17 alpha-hydroxyprogesterone caproate (17P) will
      reduce neonatal morbidity by increasing gestational age at delivery in triplet
      pregnancies. STUDY DESIGN: Double-blind, randomized clinical trial. Mothers
      carrying trichorionic-triamniotic triplets were randomly assigned (in a 2:1
      ratio) to weekly injections of 250 mg of 17P or placebo, starting at 16-22 weeks
      and continued until 34 weeks. Primary outcome was composite neonatal morbidity.
      RESULTS: Fifty-six women were randomized to 17P and 25 to placebo. Composite
      neonatal morbidity occurred with similar frequency in the 17P and placebo groups
      (38% vs 41%, respectively; P = .71). Mean gestational age at delivery was not
      affected by 17P (31.9 vs 31.8 weeks; P = .36). There were 13 midtrimester fetal
      losses with 17P vs none with placebo (P < .02). CONCLUSION: In triplet pregnancy,
      prophylactic treatment with 17P did not reduce neonatal morbidity or prolong
      gestation but was associated with increased midtrimester fetal loss.

PMID- 20816147
TI  - Cost-effective standardization of preterm labor evaluation.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of a
      standardized evidence-based protocol for preterm labor evaluation on resource use
      and obstetrics outcomes. STUDY DESIGN: We conducted a retrospective 12-month
      observational study of patients with symptoms of preterm labor at the Mayo
      Clinic. All patients underwent triage evaluation per a standardized protocol with
      a combination of cervical length measurement with contingent fetal fibronectin
      assay. RESULTS: Of 201 patients who underwent evaluation, 3 women delivered
      within 7 days, and only 1 woman delivered after a negative evaluation. Mean
      gestational age at evaluation was 29 weeks 1 day, and delivery was at 38 weeks 3
      days of gestation, with an average interval of 57.4 days until delivery. The rate
      of hospital admission was reduced by 56%, compared with the previous year; an
      estimated annual cost saving was $39,900. CONCLUSION: Implementation of a
      standardized protocol for evaluation of preterm labor reduces the rate of
      unnecessary hospital admissions for observation with consequent significant
      reduction in expenses.

PMID- 20816148
TI  - Betamethasone in pregnancy: influence of maternal body weight and multiple
      gestation on pharmacokinetics.
AB  - OBJECTIVE: The goals of the study were to estimate the pharmacokinetic parameters
      of standard dose betamethasone in a large obstetrics population and evaluate the
      effect of maternal body size and multiple gestation on the pharmacokinetic
      parameters and their observed variability. STUDY DESIGN: This was a prospective
      pharmacokinetic study. Liquid chromatography mass spectrometry was used to
      measure betamethasone plasma concentrations. Pharmacokinetic parameters and
      significant clinical covariates were estimated with mixed effect modeling.
      Bootstrap analysis confirmed validity of the model. RESULTS: Two hundred seventy
      four blood samples from 77 patients were obtained. The greatest effect on
      pharmacokinetic variability was observed with maternal lean body weight (LBW).
      The relationship between the pharmacokinetic parameters and LBW remained linear
      over a wide range of maternal body sizes. Multiple gestations did not affect the
      pharmacokinetic parameters. CONCLUSION: Individualization of betamethasone dosing
      by maternal LBW reduces variability in drug exposure. Mutiple gestations do not
      require betamethasone dosing adjustment, because pharmacokinetics are the same as
      singleton gestations.

PMID- 20816149
TI  - Cervical funneling: effect on gestational length and ultrasound-indicated
      cerclage in high-risk women.
AB  - OBJECTIVE: The purpose of this study was to assess funnel type and pregnancy
      duration in women with previous spontaneous preterm birth and cervical length <25
      mm. STUDY DESIGN: We performed a secondary analysis of a multicenter randomized
      trial of cerclage. At the randomization scan that documented short cervix, the
      presence and type of funnel (U or V) were recorded. RESULTS: One hundred forty
      seven of 301 women (49%) had funneling: V-shaped funnel, 99 women; U-shaped
      funnel, 48 women. U-shaped funnel was associated significantly with preterm birth
      at <24, <28, <35, and <37 weeks of gestation. In multivariable models that
      controlled for randomization cervical length and cerclage, women with U-shaped
      funnel delivered earlier than women with either V-shaped funnel or no funnel.
      Interaction between cerclage and U-shaped funnel was observed, and analyses that
      were stratified by cerclage showed that women with a U-shaped funnel and cerclage
      delivered at a mean of 33.8 +/- 6.6 weeks of gestation, compared with women who
      did not receive cerclage (28.9 +/- 6.9 weeks of gestation). CONCLUSION: U-shaped
      funnels in high-risk women with a short cervix are associated with earlier birth.

PMID- 20816150
TI  - Rates of labor induction without medical indication are overestimated when
      derived from birth certificate data.
AB  - OBJECTIVE: The purpose of this study was to determine the rates of late preterm
      inductions without a medical indication from birth certificate data and to
      compare them with rates that were obtained from medical charts. STUDY DESIGN: The
      Ohio Perinatal Quality Collaborative, which comprises 20 hospitals in Ohio that
      came together in 2008 for the purpose of decreasing nonmedically indicated
      scheduled deliveries, abstracted data on all scheduled births between 36 weeks
      and 38 weeks 6 days of gestation. We compared labor inductions with "elective"
      documented or no indication documented in charts to birth certificate data for
      inductions with no maternal or fetal complications recorded. RESULTS: Birth
      certificates overestimate rates of induction without medical indication compared
      with chart abstraction (11% vs 1%; P < .0001). The monthly difference between
      chart abstraction and birth certificates averages 10.1%. CONCLUSION: Birth
      certificates overestimate nonmedically indicated inductions by 11-fold. Until
      birth certificate data improve, nonmedically indicated induction rates that are
      calculated from birth certificates should be interpreted with caution.

PMID- 20816151
TI  - Gestational weight gain in consecutive pregnancies.
AB  - OBJECTIVE: The purpose of this study was to examine the association between
      gestational weight gain (GWG) in a woman's first and second pregnancies. STUDY
      DESIGN: We conducted a retrospective observational cohort study of 27,771 women
      with their first and second births in North Carolina's Pregnancy Nutrition
      Surveillance System database from 1996-2004. GWG was categorized as inadequate,
      appropriate, or excessive, according to 2009 Institute of Medicine guidelines.
      Covariate adjusted polytomous logistic regression was used to test the
      association between GWG category in the first and second pregnancy. RESULTS:
      Compared with women with appropriate GWG in their first pregnancy, women with
      excessive GWG in their first pregnancy had an odds ratio of 2.6 (95% confidence
      interval, 2.4-2.7) for excessive GWG in their second pregnancy. Women with
      inadequate GWG in their first pregnancy were similarly likely to repeat this
      category in their subsequent pregnancy. CONCLUSION: GWG category in a woman's
      first pregnancy is a significant predictor of GWG category in her subsequent
      pregnancy.

PMID- 20816152
TI  - Obesity and diabetes genetic variants associated with gestational weight gain.
AB  - OBJECTIVE: We sought to determine whether genetic variants associated with
      diabetes and obesity predict gestational weight gain. STUDY DESIGN: A total of
      960 participants in the Pregnancy, Infection, and Nutrition cohorts were
      genotyped for 27 single-nucleotide polymorphisms (SNPs) associated with diabetes
      and obesity. RESULTS: Among Caucasian and African American women (n = 960), KCNQ1
      risk allele carriage was directly associated with weight gain (P < .01). In
      Bayesian hierarchical models among Caucasian women (n = 628), we found posterior
      odds ratios >3 for inclusion of TCF2 and THADA SNPs in our models. Among African
      American women (n = 332), we found associations between risk allele carriage and
      weight gain for the THADA and INSIG2 SNPs. In Bayesian variable selection models,
      we found an interaction between the TSPAN8 risk allele and pregravid obesity,
      with lower weight gain among obese risk allele carriers. CONCLUSION: We found
      evidence that diabetes and obesity risk alleles interact with maternal pregravid
      body mass index to predict gestational weight gain.

PMID- 20816153
TI  - Randomized controlled trial of wound complication rates of subcuticular suture vs
      staples for skin closure at cesarean delivery.
AB  - OBJECTIVE: The purpose of this study was to determine the wound complication
      rates and patient satisfaction for subcuticular suture vs staples for skin
      closure at cesarean delivery. STUDY DESIGN: This was a randomized prospective
      trial. Subjects who underwent cesarean delivery were assigned randomly to
      stainless steel staples or subcuticular 4.0 Monocryl sutures. The primary
      outcomes were composite wound complication rate and patient satisfaction.
      RESULTS: A total of 435 patients were assigned randomly. Staple closure was
      associated with a 4-fold increased risk of wound separation (adjusted odds ratio
      [aOR], 4.66; 95% confidence interval [CI], 2.07-10.52; P < .001). Having a wound
      complication was associated with a 5-fold decrease in patient satisfaction (aOR,
      0.18; 95% CI, 0.09-0.37; P < .001). After confounders were controlled for, there
      was no difference in satisfaction between the treatment groups (aOR, 0.71; 95%
      CI, 0.34-1.50; P = .63). CONCLUSION: Use of staples for cesarean delivery closure
      is associated with an increased risk of wound complications. Occurrence of a
      wound complication is the most important factor that influenced patient
      satisfaction.

PMID- 20816155
TI  - Loop electrosurgical excision procedure with an intrauterine device in place.
AB  - Patients using an intrauterine device (IUD) who require a loop electrosurgical
      excision procedure (LEEP) for cervical dysplasia have traditionally had the IUD
      removed prior to the procedure. The only other options have been methods that
      lead to suboptimal sampling or risk cutting the strings. Our study suggests a
      procedure for performing the LEEP without removing the IUD, and review of the
      literature suggests that this method has not been reported before. The LEEP is
      performed using a conization electrode or a cone biopsy excisor. After noting
      that the IUD strings are of adequate length, a 0-polyglactin free tie is secured
      around the visible portion of the IUD strings without applying tension on the
      strings. A large, sterile absorbent-tipped applicator with a hollow handle
      becomes an 8 cm hollow plastic tube by removing the cotton tip with sterile
      scissors. The long end of the suture is threaded through the sterile tube.
      Without pulling on the IUD, the tube is then passed over the strings into the
      cervical canal approximately 2.5 cm to protect the strings from the excisor well
      into the cervical canal. Then, the LEEP is performed. After the specimen is
      removed, hemostasis can be obtained using a ball cautery electrode, keeping the
      protecting tube with the enclosed IUD strings out of the way. The tube is then
      carefully removed. The suture is now cut close to the polyglactin knot around the
      IUD strings, making certain not to shorten the IUD strings and making certain the
      visible length of the strings is the same as before the procedure. Ferric
      subsulfate is applied to the operative area to provide continued hemostasis.
      Follow-up for the LEEP is unchanged. This procedure may be performed on either
      levonorgestrel-releasing or copper IUDs.

PMID- 20816156
TI  - Preface. Glycobiology.

PMID- 20816157
TI  - Beta1,4-galactosyltransferase V A growth regulator in glioma.
AB  - One of the most prominent transformation-associated changes in the sugar chains
      of glycoproteins is an increase in the large N-glycans of cell surface
      glycoprotein. beta1,4-galactosyltransferase V (beta1,4GalT V) could effectively
      galactosylate the GlcNAcbeta1-->6 branch which is a marker of glioma. The
      expression of beta1,4GalT V is increased in the process of glioma development.
      beta1,4GalT V regulates the invasion, growth in vivo and in vitro of glioma
      cells. Downregulation of beta1,4GalT V expression increases the sensitivity of
      malignant glioma cells to DNA damage drugs. Furthermore, beta1,4GalT V regulates
      Ras and AKT signaling involving in glioma behaviors. Meanwhile, Ras/MAPK and
      PI3K/AKT signaling pathways are involved in the transcription regulation of
      beta1,4GalT V gene. E1AF transcription factor, a downstream target of Ras/MAPK
      and PI3K/AKT signaling pathways, regulates the transcription of beta1,4GalT V in
      cooperation with Sp1 transcription factor. The contribution of beta1,4GalT V in
      glioma development is further confirmed in glioma-initiation cells. beta1,4GalT V
      regulates the self-renewal of glioma-initiation cells. We now present evidence
      that beta1,4GalT V functions as a positive growth regulator in glioma and might
      represent a novel target in glioma therapy.

PMID- 20816159
TI  - Structural and functional analysis of chondroitin sulfate proteoglycans in the
      neural stem cell niche.
AB  - The stem cell niche plays an important role for the maintenance and
      differentiation of neural stem/progenitor cells (NSPCs). It is composed of
      distinct cell types that influence NSCPs by the release of paracrine factors, and
      a specialized extracellular matrix that structures the NSPC environment. During
      the past years, several components of the neural stem cell (NSC) niche could be
      deciphered on the molecular level. One prominent constituent is the tenascin-C
      (Tnc) glycoprotein and its isoforms that intervene in NSPC proliferation and
      differentiation. Distinct chondroitin sulfate proteoglycans (CSPGs) associate
      with Tnc in the niche territory and we could show that these have functional
      connotations in the stem cell compartment in their own rights. In this chapter,
      we give an account of the tools and methods we developed to unravel the
      structures and functions of CSPGs in the NSC niche.

PMID- 20816158
TI  - Roles of polysialic acid in migration and differentiation of neural stem cells.
AB  - Polysialic acid, a homopolymer of alpha2,8-linked sialic acid, is one of the
      carbohydrates expressed on neural precursors in the embryonic and adult brain.
      Polysialic acid, synthesized by two polysialyltransferases (ST8SiaII and
      ST8SiaIV), mainly modulates functions of the neural cell adhesion molecule
      (NCAM). Polysialic acid-deficient mice demonstrated that polysialylated NCAM
      plays crucial roles in various steps of neural development, such as cell survival
      and cell migration of neural precursors, neuronal guidance, and synapse
      formation. However, the mechanisms of the diverse phenotypes and molecules
      affected by polysialic acid remain to be defined. To study the roles of
      polysialic acid on neural stem cells, analyses of neural stem cells from
      polysialic acid-deficient and NCAM-deficient mice are useful. Here, we describe
      how to prepare neural precursor cells from mouse brain and how to analyze
      migration and differentiation of neurosphere cells in vitro.

PMID- 20816160
TI  - Transcript analysis of stem cells.
AB  - Quantitative real-time polymerase chain reaction (qRT-PCR) is a flexible and
      scalable method for analyzing transcript abundance that can be used at a single
      gene or high-throughput (>100 genes) level. Information obtained from this
      technique can be used as an indicator of potential regulation of glycosylation at
      the transcript level when combined with glycan structural or protein abundance
      data. This chapter describes detailed methods to design and perform qRT-PCR
      analyses and provides examples of information that can be obtained from the
      technique.

PMID- 20816161
TI  - Directing stem cell trafficking via GPS.
AB  - The success of stem-cell-based regenerative therapeutics critically hinges on
      delivering relevant stem/progenitor cells to sites of tissue injury. To achieve
      adequate parenchymal infiltration following intravascular administration, it is
      first necessary that circulating cells bind to target tissue endothelium with
      sufficient strength to overcome the prevailing forces of hemodynamic shear. The
      principal mediators of these shear-resistant binding interactions consist of a
      family of C-type lectins known as "selectins" that bind discrete sialofucosylated
      glycans on their respective ligands. One member of this family, E-selectin, is an
      endothelial molecule that is inducibly expressed on postcapillary venules at all
      sites of tissue injury, but is also constitutively expressed on the luminal
      surface of bone marrow and dermal microvascular endothelium. Most stem/progenitor
      cells express high levels of CD44, and, in particular, human hematopoietic stem
      cells express a specialized sialofucosylated glycoform of CD44 known as
      "hematopoietic cell E-/L-selectin ligand" (HCELL) that functions as a potent E
      selectin ligand. This chapter describes a method called "glycosyltransferase
      programmed stereosubstitution" (GPS) for custom-modifying CD44 glycans to create
      HCELL on the surface of living cells that natively lack HCELL. Ex vivo glycan
      engineering of HCELL via GPS licenses trafficking of infused cells to endothelial
      beds that express E-selectin, thereby enabling efficient vascular delivery of
      stem/progenitor cells to sites where they are needed.

PMID- 20816162
TI  - Functional assays for the molecular chaperone cosmc.
AB  - Mucin type O-glycosylation involves sequential actions of several
      glycosyltransferases in the Golgi apparatus. Among those enzymes, a single gene
      product termed core 1 beta3-galactosyltransferase (T-synthase) in vertebrates is
      the key enzyme that converts the precursor Tn antigen GalNAcalpha1-Ser/Thr to the
      core 1 structure, Galbeta1-3GalNAcalpha1-Ser/Thr, also known as T antigen. This
      represents the most common structure within typical O-glycans of membrane and
      secreted glycoproteins. Formation of the active T-synthase requires that it
      interacts with Core 1 beta3Gal-T Specific Molecular Chaperone (Cosmc), which is a
      specific molecular chaperone in the endoplasmic reticulum (ER). T-synthase
      activity is commonly measured by its ability to transfer [3H]Gal from UDP-[3H]Gal
      to an artificial acceptor GalNAcalpha-1-O-phenyl to form [3H]Galbeta1
      3GalNAcalpha-1-O-phenyl, which can then be isolated and quantified. Because the
      primary function of Cosmc is to form active T-synthase, the activity of Cosmc is
      assessed indirectly by its ability to promote formation of active T-synthase when
      it is coexpressed with T-synthase in cells lacking functional Cosmc. Such cells
      include insect cells, which constitutively lack Cosmc, and Cosmc-deficient
      mammalian cell lines. Cosmc is encoded by the X-linked Cosmc gene (Xq24 in human,
      Xc3 in mice), thus, acquired mutations in Cosmc, which have been observed in
      several human diseases, such as Tn syndrome and cancers, cause a loss of T
      synthase, and expression of the Tn antigen. The methods described here allow the
      functional activities of such mutated Cosmc (mCosmc) to be measured and compared
      to wild-type (wtCosmc).

PMID- 20816163
TI  - Core 3-derived O-glycans are essential for intestinal mucus barrier function.
AB  - O-Glycans are primary components of the intestinal mucins that form the mucus gel
      layer overlying the gut epithelium. Core 3-derived O-glycans, which are one of
      the major types of O-glycans, are primarily expressed in colon. To investigate
      the biological function of core 3-derived O-glycans, we engineered mice lacking
      core 3 beta1,3-N-acetylglucosaminyltransferase (C3GnT), an enzyme predicted to be
      important in synthesis of core 3-derived O-glycans. Disruption of the C3GnT gene
      eliminated core 3-derived O-glycans. C3GnT-deficient mice displayed a discrete,
      colon-specific reduction in Muc2 protein and increased permeability of the
      intestinal barrier. Moreover, these mice were highly susceptible to experimental
      triggers of colitis. These data reveal a requirement for core 3-derived O-glycans
      in colon mucus barrier function.

PMID- 20816164
TI  - Core3 glycan as tumor suppressor.
AB  - Recent studies demonstrated that mucin type O-glycans have important roles in
      tumorigenesis. Although several papers have been reported that increased core2 O
      glycan is detected with several cancer progression (Dalziel, et al., 2001;
      Machida, et al., 2001), very little is known about the function of core3 O-glycan
      in tumorigenesis. Core3 O-glycan is synthesized by beta1, 3-N
      acetylglucosamintraseferase 6 (core3 synthase). To understand the function of
      core3 O-glycan in cancer, ectopic expression of core3 synthase to prostate cancer
      cells were used for tumor formation assay. Since core3 expressing prostate cancer
      cells show decreased tumor formation and metastasis to lymph node through
      attenuating the maturation and heterodimerization of integrin alpha2beta1, those
      findings indicate that core3 structure acts as tumor suppressor through
      regulating the integrin functions. In this chapter, we discuss methods used to
      reveal the mechanisms how core3 glycan act as tumor suppressor.

PMID- 20816165
TI  - Characterization of mice with targeted deletion of the gene encoding core 2
      beta1,6-N-acetylglucosaminyltransferase-2.
AB  - The three glycosyltransferases of the Core 2 beta1,6-N
      acetylglucosaminyltransferase (C2GnT) family, C2GnT1, C2GnT2, and C2GnT3, are
      able to initiate the Core 2 branch of O-glycans. However, C2GnT2, which is highly
      expressed in the digestive tract, has a broader acceptor substrate specificity
      that allows it to also generate Core 4 O-glycans and I branches. We discovered
      that C2GnT2 KO mice have decreased mucosal barrier function in the digestive
      tract, reduced levels of circulating IgGs and fecal IgA, and increased
      susceptibility to experimental colitis. Mass spectrometric analyses also revealed
      that C2GnT2 KO mice had a reduction in Core 2 O-glycans in the digestive tract
      with a corresponding increase in elongated Core 1 O-glycans. Unexpectedly, we saw
      that the loss of C2GnT2 and especially the loss of all three C2GnTs resulted in
      the expression of elongated O-mannose structures in the stomach, suggesting that
      the elongation of these structures is controlled by competition for UDP-GlcNAc
      [Stone, E. L., Ismail, M. N., Lee, S. H., Luu, Y., Ramirez, K., Haslam, S. M.,
      Ho, S. B., Dell, A., Fukuda, M. and Marth, J. D. (2009). Glycosyltransferase
      function in Core 2-type protein O-glycosylation. Mol. Cell. Biol. 29, 3370-3782].

PMID- 20816166
TI  - Analyzing physiological function of polypeptide GalNAcT-1-deficient mice in
      humoral immunity.
AB  - A family of polypeptide GalNAc transferases (ppGalNAcTs) initiates protein O
      glycosylation. The ppGalNAcT gene family is large; at least 15 ppGalNAcT isozymes
      have been cloned so far and each of them may have important and distinctive
      physiologic functions. ppGalNAcT-1, which is highly expressed in many tissues and
      cell types, is the first member of the ppGalNAcT family to be cloned. In order to
      understand the physiologic role of ppGalNAcT-1, we generated and characterized
      mice lacking this isozyme. We found that ppGalNAcT-1 plays key roles in germinal
      center (GC) B lymphocyte apoptosis in the modulation of humoral immune response.
      In this chapter, in vitro and in vivo systems to assess the B lymphocyte function
      of ppGalNAcT-1-deficient mice are discussed. In addition, detailed information on
      the immunohistochemistry of GC is also described.

PMID- 20816167
TI  - Beta3GnT2 (B3GNT2), a major polylactosamine synthase: analysis of B3GNT2
      deficient mice.
AB  - The polylactosamine structure is a fundamental structure of carbohydrate chains
      and carries a lot of biofunctional carbohydrate epitopes. To investigate the
      biological function of polylactosamine chains, here we generated and analyzed
      knockout mice lacking the gene B3gnt2, which encodes a major polylactosamine
      synthase. In beta1,3-N-acetylglucosaminyltransferase (B3gnt2) B3gnt2-deficient
      (B3gnt2-/-) mice, the number of polylactosamine structures was markedly lower
      than in wild-type mice. Flow cytometry, LEL lectin-blotting, and glycan analysis
      by metabolic labeling demonstrated that the amount of polylactosamine chains on N
      glycans was greatly reduced in the tissues of B3gnt2-/- mice. We examined whether
      immunological abnormalities were present in B3gnt2-/- mice. We screened
      polylactosamine-carrying molecules of wild-type mice by lectin microarray
      analysis and found that polylactosamine was present on CD28 and CD19, two
      established immune co-stimulatory molecules. Polylactosamine levels on these
      molecules were lower in B3gnt2-/- mice than in wild-type mice. B3gnt2-/- T cells
      were more sensitive to the induction of intracellular Ca2+ flux on stimulation
      with anti-CD3epsilon/CD28 antibodies and proliferated more strongly than wild
      type T cells. B3gnt2-/- B cells also showed hyperproliferation on BCR
      stimulation. These results showed that hyperactivation of lymphocytes occurred
      due to a lack of polylactosamine on receptor molecules in B3gnt2-/- mice. This
      finding indicates that polylactosamine has an important role in immunological
      biofunctions. We can therefore attempt to identify the in vivo biological
      function of glycans using glycogene-deficient mice.

PMID- 20816168
TI  - Targeted genetic inactivation of N-acetylglucosaminyltransferase-IVa impairs
      insulin secretion from pancreatic beta cells and evokes type 2 diabetes.
AB  - The biological significance of protein N-glycosylation has been elucidated using
      a mouse model bearing a genetic mutation of N-acetylglucosaminyltransferases
      (GnTs), which initiate the formation of specific branch structures on the mannose
      core of N-glycans. These glycosylation defects evoked a variety of abnormalities
      and disorders in specific cell types, tissues, and the whole body, reflecting
      functional requirements. N-Acetylglucosaminyltransferase-IVa (GnT-IVa) initiates
      the GlcNAcbeta1-4 branch synthesis on the Manalpha1-3 arm of the N-glycan core
      thereby increasing N-glycan branch complexity. To investigate the physiological
      function of GnT-IVa, we engineered and characterized GnT-IVa-deficient mice. GnT
      IVa-deficient mice showed a metabolic disorder subsequently diagnosed as type 2
      diabetes. In this chapter, methods for characterizing GnT-IVa-deficient mice by
      physiological analyses to detect metabolic alterations and biochemical analyses
      using primary isolated pancreatic beta cells are summarized and discussed.

PMID- 20816169
TI  - The Ashwell-Morell receptor.
AB  - The Ashwell-Morell receptor (AMR) of hepatocytes, originally termed the hepatic
      asialoglycoprotein receptor, was the first cellular receptor to be identified and
      isolated and the first lectin to be detected in mammals. It is one of the
      multiple lectins of the C-type lectin family involved in recognition, binding,
      and clearance of asialoglycoproteins. We recently identified endogenous ligands
      of the AMR as desialylated prothrombotic components, including platelets and von
      Willebrand Factor [Ellies L. G., Ditto D., Levy G. G., Wahrenbrock M., Ginsburg
      D., Varki A., Le D. T., and Marth J. D. (2002). Sialyltransferase ST3Gal-IV
      operates as a dominant modifier of hemostasis by concealing asialoglycoprotein
      receptor ligands. Proc. Natl. Acad. Sci. USA 99: pp. 10042-10047; Grewal, P. K.
      Uchiyama, S., Ditto, D., Varki, N., Le, D. T., Nizet, V., Marth, J. D. (2008).
      The Ashwell receptor mitigates the lethal coagulopathy of sepsis. Nat. Medicine
      14, pp. 648-655]. Among these components, clearance by the liver's AMR is
      enhanced by exposure of terminal galactose on the glycan chains. A physiological
      role for engaging the AMR in rapid clearance was identified as mitigating
      disseminating intravascular coagulopathy in sepsis to promote survival. This
      chapter overviews the endogenous ligands of the AMR as components of the
      coagulatory system, describes clearance mechanisms of the liver, and details
      hematology and coagulation assays used in mouse coagulation studies.

PMID- 20816170
TI  - Roles of GlcNAc-6-O-sulfotransferases in lymphoid and nonlymphoid tissues.
AB  - Recent studies using sulfotransferase-deficient mice have revealed various
      physiological functions of sulfated glycans. Studies using gene-targeted mice
      deficient in both N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST)-1 and
      GlcNAc6ST-2 showed that these sulfotransferases play critical roles in lymphocyte
      homing. Recent studies indicated that GlcNAc6ST-2 is expressed not only in lymph
      node high endothelial venules but also in the colonic epithelial cells in mice,
      and that this sulfotransferase plays a critical role in GlcNAc-6-O-sulfation of
      the colonic-mucins, as revealed by liquid chromatography coupled to electrospray
      ionization tandem mass spectrometry of the colonic-mucin O-glycans from wild-type
      (WT) and GlcNAc6ST-2-deficient mice. After induction of colitis by dextran
      sulfate sodium, significantly more leukocyte infiltration was observed in the
      colon of GlcNAc6ST-2-deficient mice than in that of WT mice. These studies
      demonstrate that GlcNAc-6-O-sulfotransferases play important roles not only in
      lymphoid tissues but also in nonlymphoid tissues. This chapter describes
      experimental procedures for assessing the functions of GlcNAc-6-O
      sulfotransferases using gene-targeted mice.

PMID- 20816171
TI  - Core O-glycans required for lymphocyte homing gene knockout mice of core 1
      beta1,3-N-acetylglucosaminyltransferase and core 2 N
      acetylglucosaminyltransferase.
AB  - Mucin-type O-glycans are synthesized by sequential reaction of
      glycosyltransferases that have different substrate specificities. To know the
      significance of specific O-glycan structures, many researchers have been making
      mice deficient in corresponding enzymes for the synthesis of the O-glycan
      structures. Here we describe the analysis of gene knockout mice of core 2
      branching enzyme (core 2 N-acetylglucosaminyltransferase, Core2GlcNAcT) and core
      1 extension enzyme (core 1 beta1,3-N-acetylglucosaminyltransferase, Core1
      beta3GlcNAcT). Because mucin-type O-glycans present sialyl Lewis X (sLeX) and
      sulfated version of the glycans, which are L-selectin ligands, at the reducing
      end, the amounts of the ligands of these knockout mice would be reduced. The
      methods described here are to analyze the interaction between L-selectin and its
      ligand 6-sulfo sLeX such as lymphocyte homing assay, staining of frozen section,
      and blotting using L- and E-selectin-IgM chimeric proteins.

PMID- 20816172
TI  - Immunohistochemical analysis of carbohydrate antigens in chronic inflammatory
      gastrointestinal diseases.
AB  - Over the last four decades, immunohistochemistry (IHC) has become an invaluable
      technique to detect antigens in tissue sections. Compared to Western blotting
      analysis, IHC is advantageous in determining histological distribution and
      localization of the antigen. Another advantage, if one can access human formalin
      fixed paraffin-embedded (FFPE) blocks of disease tissues, is that IHC makes it
      possible to analyze diseases retrospectively from archived pathological tissue
      specimens. In this chapter, we describe protocols used for both conventional and
      multiple immunostainings using FFPE tissue sections, which have been used for
      quantitative analysis of high endothelial venule (HEV)-like vessels and
      lymphocyte subsets attached to HEV-like vessels in our studies of chronic
      inflammatory gastrointestinal diseases. We also describe in detail a protocol
      using an L-selectinIgM chimera in situ binding assay on FFPE tissue sections for
      functional detection of L-selectin ligand carbohydrates expressed on HEV-like
      vessels. After presenting each protocol, we provide practical examples for its
      use obtained from our studies.

PMID- 20816173
TI  - Genetic defects in muscular dystrophy.
AB  - The muscular dystrophies are a group of neuromuscular disorders associated with
      muscle weakness and wasting, which in many forms can lead to loss of ambulation
      and premature death. A number of muscular dystrophies are associated with loss of
      proteins required for the maintenance of muscle membrane integrity, in particular
      with proteins that comprise the dystrophin-associated glycoprotein (DAG) complex.
      Proper glycosylation of O-linked mannose chains on alpha-dystroglycan, a DAG
      member, is required for the binding of the extracellular matrix to dystroglycan
      and for proper DAG function. A number of congenital disorders of glycosylation
      have now been described where alpha-dystroglycan glycosylation is altered and
      where muscular dystrophy is a predominant phenotype. Glycosylation is also
      increasingly being appreciated as a genetic modifier of disease phenotypes in
      many forms of muscular dystrophy and as a target for the development of new
      therapies. Here we will review the mouse models available for the study of this
      group of diseases and outline the methodologies required to describe disease
      phenotypes.

PMID- 20816174
TI  - POMT1 is essential for protein O-mannosylation in mammals.
AB  - Over the past decade it has emerged that O-mannosyl glycans are not restricted to
      yeast and fungi but are also present in higher eukaryotes up to humans. In
      mammals, the protein O-mannosyltransferases POMT1 and POMT2 act as a heteromeric
      complex to initiate O-mannosylation in the endoplasmic reticulum. In humans,
      mutations in POMT1 and POMT2 result in hypoglycosylation of alpha-dystroglycan
      (alpha-DG) thereby abolishing its binding to extracellular matrix ligands such as
      laminin. As a consequence, POMT mutations cause a heterogeneous group of severe
      recessive congenital muscular dystrophies in humans. However, little is known
      about the function of O-mannosyl glycans in mammals apart from its crucial role
      for the ligand binding abilities of alpha-DG. In this chapter we discuss the
      methods used to analyze the expression of Pomt1 in adult mouse organs and during
      embryo development. Further, we describe the generation and immunohistochemical
      analysis of Pomt1 knockout mice.

PMID- 20816175
TI  - POMGnT1, POMT1, and POMT2 mutations in congenital muscular dystrophies.
AB  - Alpha-dystroglycanopathies are a group of rare inherited neuromuscular disorders
      characterized by reduced glycosylation of alpha-dystroglycan (alpha-DG).
      Mutations in six genes (POMT1, POMT2, POMGNT1, FKTN, FKRP, and LARGE) have been
      identified in patients with alpha-dystroglycanopathies. Due to an extremely broad
      clinical spectrum and relatively poor phenotype-genotype correlation, diagnosis
      of alpha-dystroglycanopathies is difficult and requires searching for mutations
      gene by gene. At present, of the six proteins involved on alpha
      dystroglycanopathies, the function of the gene products is only known for POMT1,
      POMT2, and POMGnT1, all responsible for the O-mannosylglycan biosynthesis. This
      chapter describes the assay protocols to diagnose patients with alpha
      dystroglycanopathy by measuring glycosyltransferase activity.

PMID- 20816176
TI  - Cellular and molecular characterization of abnormal brain development in protein
      o-mannose N-acetylglucosaminyltransferase 1 knockout mice.
AB  - Protein O-mannose N-acetylglucosaminyltransferase 1 (POMGnT1) is an enzyme that
      catalyzes the transfer of N-acetylglucosamine to O-mannose of glycoproteins. It
      is involved in posttranslational modification of alpha-dystroglycan (alpha-DG).
      POMGnT1-null mice were generated by gene trapping with a retroviral vector
      inserted into exon 2 of the POMGnT1 gene. Expression of POMGnT1 was completely
      disrupted as evidenced by absence of its mRNA expression. POMGnT1 knockout mice
      were viable but with reduced fertility and variable lifespan. The functional
      glycosylated form of alpha-DG was markedly reduced in POMGnT1 knockout mice along
      with impaired alpha-DG-laminin binding activity. Multiple developmental defects
      in muscle, brain, and eye were observed. In addition, the knockout mice exhibited
      extensive abnormalities in the neocortex, including changed neuron distribution,
      presence of ectopic fibroblasts, and GFAP-positive reactive astrocytes. Analysis
      of POMGnT1 knockout neocortex at several developmental stages revealed that these
      defects were secondary to disruptions of the pial basement membrane.

PMID- 20816177
TI  - Investigating the functions of LARGE: lessons from mutant mice.
AB  - The Large gene encodes a predicted glycosyltransferase of undefined biological
      activity. However, one important target of the protein is known, alpha
      dystroglycan. This protein is a key component of the dystrophin-associated
      glycoprotein in skeletal muscle, which links cytoskeletal actin to the
      extracellular matrix (ECM), stabilizing the muscle sarcolemmal membrane. alpha
      Dystroglycan binds to extracellular proteins such as laminin through a heavily
      glycosylated mucin-like domain. Functional Large protein is required for full
      glycosylation and ligand-binding activity of dystroglycan. The role of Large in
      this pathway was identified by positional cloning of the mutation in the
      myodystrophy mouse, an animal model of muscular dystrophy that also has defects
      in the central and peripheral nervous system and retinal abnormalities. Mice
      deficient in Large are models for a group of human disorders that have defective
      alpha-dystroglycan glycosylation.

PMID- 20816178
TI  - A tumor suppressor function of laminin-binding alpha-dystroglycan.
AB  - Interaction of epithelial cells with basement membrane (BM) is mediated by cell
      adhesion molecules, which regulate cell proliferation, motility, and
      differentiation by integrating signals from extracellular matrix and soluble
      factors. alpha-Dystroglycan (alpha-DG) is one of the most important adhesion
      molecules in epithelial cell-BM interaction. alpha-DG serves as the cell surface
      receptor for several major BM proteins, including laminin, perlecan, and agrin.
      The laminin G-like domain in all these proteins binds to a unique glycan
      structure, so-called laminin-binding glycan, attached to alpha-DG with high
      affinity. Formation of the laminin-binding glycan is required for the BM
      assembly, and loss or deficiency of the glycan causes muscular dystrophy. We
      studied the role of this alpha-DG-specific glycan modification in tumor
      development, and identified a tumor suppressor function of the laminin-binding
      alpha-DG. In this chapter, we describe methods used to isolate the cell
      populations from human prostate cancer cell line PC3 and characterize their
      potentials in tumor formation and metastasis in vitro and in vivo.

PMID- 20816179
TI  - Tumor formation assays.
AB  - Animal experiments are necessary to confirm and demonstrate the reliability of
      the results of in vitro assays and to reveal any unexpected effects in the living
      body. Tumor invasion and metastasis consist of multistep and complex cascades.
      Moreover, conflictive interactions between cancer cells and host immune system
      exist in the living body. Therefore, tumor formation assay is an essential
      technique in tumor biology. Methods used in tumor formation assay include
      injection and inoculation, and considerable skill is required to perform these
      basic techniques. Injections and inoculations are categorized according to the
      target site: intraperitoneal (IP), intravenous (IV), subcutaneous (SC), footpad
      (FP), and targeted organ inoculation. Tumor cell injections and inoculations are
      standard methods for the evaluation of the malignant potential of cancer cells.
      IP injection is a useful and uncomplicated method for drug administration, SC
      inoculation is used to evaluate tumor growth and size, FP inoculation to estimate
      lymph nodule metastasis, and IV injection into the tail vein to evaluate the
      metastatic potential for lung colonization. Using immune-deficiency mice, we can
      address possible roles of carbohydrate antigens against host immune system. In
      this chapter, we describe details of the materials and methods that can be used
      for injection (IP and IV) and inoculation (SC, FP, testis, and prostate) in mice.

PMID- 20816180
TI  - Genetics of asthma and allergy: what have we learned?
AB  - The overall purpose of this review is to present an update on genetic approaches
      to understanding the susceptibility and expression (severity) of common diseases,
      such as asthma and allergy. Five key questions are addressed in this review: (1)
      What phenotypes are being studied? Multiple disease phenotypes in carefully
      characterized patients are required. (2) Are the same genes that are important in
      disease susceptibility important in disease severity? (3) Are there racial
      differences in disease expression and genetic susceptibility? (4) Are the genes
      important in normal variation in lung function important in asthma severity? (5)
      Are the genes important in other common diseases, such as chronic inflammatory
      diseases or chronic obstructive pulmonary disease, important in asthma or
      allergy? In addition, a discussion of some of current areas of research is
      presented, including the issue that current genome-wide association study results
      do not account for a significant portion of trait variability, the potential role
      of rare variants and large genome-sequencing studies, and pharmacogenetics: is
      there a role for basing treatment decisions on the results of genetic testing?
      Finally, the potential usefulness of DNA, personalized medicine, is discussed.

PMID- 20816183
TI  - In utero smoke (IUS) exposure has been associated with increased prevalence of
      asthma and reduced lung function in healthy children.

PMID- 20816182
TI  - Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision.
AB  - BACKGROUND: Allergic rhinitis represents a global health problem affecting 10% to
      20% of the population. The Allergic Rhinitis and its Impact on Asthma (ARIA)
      guidelines have been widely used to treat the approximately 500 million affected
      patients globally. OBJECTIVE: To develop explicit, unambiguous, and transparent
      clinical recommendations systematically for treatment of allergic rhinitis on the
      basis of current best evidence. METHODS: The authors updated ARIA clinical
      recommendations in collaboration with Global Allergy and Asthma European Network
      following the approach suggested by the Grading of Recommendations Assessment,
      Development and Evaluation working group. RESULTS: This article presents
      recommendations about the prevention of allergic diseases, the use of oral and
      topical medications, allergen specific immunotherapy, and complementary
      treatments in patients with allergic rhinitis as well as patients with both
      allergic rhinitis and asthma. The guideline panel developed evidence profiles for
      each recommendation and considered health benefits and harms, burden, patient
      preferences, and resource use, when appropriate, to formulate recommendations for
      patients, clinicians, and other health care professionals. CONCLUSION: These are
      the most recent and currently the most systematically and transparently developed
      recommendations about the treatment of allergic rhinitis in adults and children.
      Patients, clinicians, and policy makers are encouraged to use these
      recommendations in their daily practice and to support their decisions.

PMID- 20816181
TI  - Environmental epigenetics of asthma: an update.
AB  - Asthma, a chronic inflammatory disorder of the airway, is influenced by interplay
      between genetic and environmental factors now known to be mediated by
      epigenetics. Aberrant DNA methylation, altered histone modifications, specific
      microRNA expression, and other chromatin alterations orchestrate a complex early
      life reprogramming of immune T-cell response, dendritic cell function, macrophage
      activation, and a breach of airway epithelial barrier that dictates asthma risk
      and severity in later life. Adult-onset asthma is under analogous regulation. The
      sharp increase in asthma prevalence over the past 2 or 3 decades and the large
      variations among populations of similar racial/ethnic background but different
      environmental exposures favors a strong contribution of environmental factors.
      This review addresses the fundamental question of whether environmental
      influences on asthma risk, severity, and steroid resistance are partly due to
      differential epigenetic modulations. Current knowledge on the epigenetic effects
      of tobacco smoke, microbial allergens, oxidants, airborne particulate matter,
      diesel exhaust particles, polycyclic aromatic hydrocarbons, dietary methyl donors
      and other nutritional factors, and dust mites is discussed. Exciting findings
      have been generated by rapid technological advances and well-designed
      experimental and population studies. The discovery and validation of epigenetic
      biomarkers linked to exposure, asthma, or both might lead to better epigenotyping
      of risk, prognosis, treatment prediction, and development of novel therapies.

PMID- 20816184
TI  - Evaluation of airway reactivity and immune characteristics as risk factors for
      wheezing early in life.
AB  - BACKGROUND: Childhood asthma is most often characterized by recurrent wheezing,
      airway hyperreactivity, and atopy; however, our understanding of these
      relationships from early in life remains unclear. Respiratory tract illnesses and
      atopic sensitization early in life might produce an interaction between innate
      and acquired immune responses, leading to airway inflammation and heightened
      airway reactivity. OBJECTIVE: We hypothesized that premorbid airway reactivity
      and immunologic characteristics of infants without prior episodes of wheezing
      would be associated with subsequent wheezing during a 1-year follow-up. METHODS:
      One hundred sixteen infants with chronic dermatitis were enrolled before episodes
      of wheezing. Airway reactivity, allergen-specific IgE levels, cytokine production
      by stimulated PBMCs, and percentages of dendritic cells were measured on entry,
      and airway reactivity was reassessed at the 1-year follow-up. Linear regression
      models were used to evaluate a predictor's effect on continuous outcomes.
      RESULTS: Milk sensitization, egg sensitization, or both were associated with
      heightened airway reactivity before wheezing and after the onset of wheezing;
      however, these factors were not associated with an increased risk of wheezing.
      There was an interaction between initial airway reactivity and wheezing as a
      determinant of airway reactivity at follow-up. In addition, cytokine production
      by stimulated PBMCs was a risk factor for wheezing, whereas increased percentages
      of conventional dendritic cells were protective against wheezing. CONCLUSION: Our
      data in a selected cohort of infants support a model with multiple risk factors
      for subsequent wheezing that are independent of initial airway reactivity;
      however, the causative factors that produce wheezing very early in life might
      contribute to heightened airway reactivity.

PMID- 20816185
TI  - Multitrigger versus episodic wheeze in toddlers: new phenotypes or severity
      markers?

PMID- 20816186
TI  - Gender differences in asthma development and remission during transition through
      puberty: the TRacking Adolescents' Individual Lives Survey (TRAILS) study.
AB  - BACKGROUND: During puberty, a gender shift in asthma prevalence occurs, with a
      preponderance of boys before puberty. The mechanisms underlying this gender shift
      are unclear. OBJECTIVES: We assessed associations of pubertal stages and
      transition through puberty with (1) the prevalence, incidence, and remission of
      asthma in male and female subjects; (2) total IgE levels; and (3) peak expiratory
      flow (PEF) fall during a shuttle run test (SRT). METHODS: In the TRacking
      Adolescents' Individual Lives Survey study (n = 2,230; 51% female subjects),
      associations between pubertal stages and the prevalence, incidence, and remission
      of asthma were tested by using logistic regression and generalized estimating
      equations at a mean age of 11.1 (SD, 0.6), 13.6 (SD, 0.5), and 16.3 (SD, 0.7)
      years. Multiple linear regression analyses were used to study log-transformed
      total IgE levels and PEF fall during a SRT dependent on early versus late
      pubertal stages at a mean age of 16.3 years. RESULTS: The prevalence of asthma
      was similar in boys (7.7%) and girls (7.4%) at a mean age of 11.1 years. The
      prevalence of asthma was significantly higher in female (6.2%) than male (4.3%)
      subjects at 16.3 years of age. There were no significant associations between
      transition of pubertal stages and the presence of asthma, either cross
      sectionally or longitudinally. Pubertal stages and log-transformed total IgE
      levels or PEF fall during a SRT at age 16.3 years were not correlated.
      CONCLUSIONS: A shift in the prevalence of asthma occurs between 11.1 and 16.3
      years, which is due to both an increased incidence and decreased remission of
      asthma in female compared with male subjects. Pubertal stages could not be proved
      to explain the gender shift in asthma prevalence.

PMID- 20816187
TI  - Randomized controlled trial of adherence with single or combination inhaled
      corticosteroid/long-acting beta-agonist inhaler therapy in asthma.
AB  - BACKGROUND: The inhaled corticosteroid (ICS)/long-acting beta-agonist (LABA)
      combination inhaler has the potential to improve adherence with ICS therapy in
      asthma. OBJECTIVE: To determine whether ICS/LABA combination inhaler therapy
      improves adherence compared with separate inhaler use. METHODS: In a 24-week
      randomized controlled parallel group study, 111 subjects were prescribed 125
      microg fluticasone dipropionate (FP) and 25 microg salmeterol, 2 actuations twice
      daily through either a combination inhaler or separate inhalers concurrently.
      Medication use was recorded by covert electronic monitors. The primary outcome
      variable was adherence during the final 6-week period, defined as the number of
      doses taken as a percentage of those prescribed. RESULTS: Complete adherence data
      from the final 6-week period were available for 49 and 54 subjects in the
      separate and combination groups, respectively. The mean (SD) adherence was 73.7%
      (36.0) for FP, 76.7% (30.5) for salmeterol, and 82.4% (24.5) for FP/salmeterol.
      There were no significant differences in adherence between FP/salmeterol and FP (
      8.7%; 95% CI, -10.6 to 3.3) and salmeterol (-5.6%; 95% CI, -16.4 to 5.1). There
      was no significant difference in overuse among the FP, salmeterol, or
      FP/salmeterol groups. In 2 (4%) of 49 subjects, salmeterol was effectively taken
      as monotherapy during a 6-week period. CONCLUSION: In the setting of a randomized
      controlled trial, use of a combination ICS/LABA inhaler does not markedly
      increase adherence above that observed with separate inhaler use. LABA
      monotherapy was observed in a small proportion of patients prescribed ICS and
      LABA therapy via separate inhalers.

PMID- 20816188
TI  - Atopic asthmatic subjects but not atopic subjects without asthma have enhanced
      inflammatory response to ozone.
AB  - BACKGROUND: Asthma is a known risk factor for acute ozone-associated respiratory
      disease. Ozone causes an immediate decrease in lung function and increased airway
      inflammation. The role of atopy and asthma in modulation of ozone-induced
      inflammation has not been determined. OBJECTIVE: We sought to determine whether
      atopic status modulates ozone response phenotypes in human subjects. METHODS:
      Fifty volunteers (25 healthy volunteers, 14 atopic nonasthmatic subjects, and 11
      atopic asthmatic subjects not requiring maintenance therapy) underwent a 0.4-ppm
      ozone exposure protocol. Ozone response was determined based on changes in lung
      function and induced sputum composition, including airway inflammatory cell
      concentration, cell-surface markers, and cytokine and hyaluronic acid
      concentrations. RESULTS: All cohorts experienced similar decreases in lung
      function after ozone. Atopic and atopic asthmatic subjects had increased sputum
      neutrophil numbers and IL-8 levels after ozone exposure; values did not
      significantly change in healthy volunteers. After ozone exposure, atopic
      asthmatic subjects had significantly increased sputum IL-6 and IL-1beta levels
      and airway macrophage Toll-like receptor 4, Fc(epsilon)RI, and CD23 expression;
      values in healthy volunteers and atopic nonasthmatic subjects showed no
      significant change. Atopic asthmatic subjects had significantly decreased IL-10
      levels at baseline compared with healthy volunteers; IL-10 levels did not
      significantly change in any group with ozone. All groups had similar levels of
      hyaluronic acid at baseline, with increased levels after ozone exposure in atopic
      and atopic asthmatic subjects. CONCLUSION: Atopic asthmatic subjects have
      increased airway inflammatory responses to ozone. Increased Toll-like receptor 4
      expression suggests a potential pathway through which ozone generates the
      inflammatory response in allergic asthmatic subjects but not in atopic subjects
      without asthma.

PMID- 20816190
TI  - Exposure to community violence is associated with asthma hospitalizations and
      emergency department visits.
AB  - BACKGROUND: Exposure to community violence (ECV) has been associated with asthma
      morbidity of children living in inner-city neighborhoods. OBJECTIVE: To examine
      with prospective longitudinal data whether ECV is independently associated with
      asthma-related health outcomes in adults. METHODS: Adults with moderate-severe
      asthma, recruited from clinics serving inner-city neighborhoods, completed
      questionnaires covering sociodemographics, asthma severity, and ECV and were
      followed for 26 weeks. Longitudinal models were used to assess unadjusted and
      adjusted associations of subsequent asthma outcomes (emergency department [ED]
      visits, hospitalizations, FEV(1), quality of life). RESULTS: A total of 397
      adults, 47 +/- 14 years old, 73% women, 70% African American, 7% Latino, mean
      FEV(1) 66% +/- 19%, 133 with hospitalizations and 222 with ED visits for asthma
      in the year before entry, were evaluated. Ninety-one reported ECV. Controlling
      for age, sex, race/ethnicity, and household income, those exposed to violence had
      2.27 (95% CI, 1.32-3.90) times more asthma-related ED visits per month and 2.49
      (95% CI, 1.11-5.60) times more asthma-related hospitalizations per month over the
      26-week study period compared with those unexposed. Violence-exposed participants
      also had 1.71 (95% CI, 1.14-2.56) times more overall ED visits per month and 1.72
      (95% CI, 0.95-3.11) times more overall hospitalizations per month from any cause.
      Asthma-related quality of life was lower in the violence-exposed participants (
      0.40; 95% CI, -0.77 to -0.025; P = .04). Effect modification by depressive
      symptoms was only statistically significant for the ECV association with overall
      ED visits and quality-of-life outcomes (P < .01). CONCLUSION: In adults, ECV is
      associated with increased asthma hospitalizations and emergency care for asthma
      or any condition and with asthma-related quality of life.

PMID- 20816191
TI  - Children with allergic and nonallergic rhinitis have a similar risk of asthma.
AB  - BACKGROUND: Both allergic and nonallergic rhinitis have been associated with
      increased prevalence of asthma. OBJECTIVE: To characterize asthma and
      intermediary asthma endpoints in young children with allergic and nonallergic
      rhinitis. METHODS: Thirty-eight 7-year-old children with allergic rhinitis, 67
      with nonallergic rhinitis, and 185 without rhinitis from the Copenhagen
      Prospective Study on Asthma in Childhood birth cohort were compared for
      prevalence of asthma, eczema, food sensitization, filaggrin null-mutations, total
      IgE, blood eosinophil count, fractional exhaled nitric oxide (FeNO), lung
      function, and bronchial responsiveness. RESULTS: Children with allergic rhinitis
      compared with asymptomatic controls had increased prevalence of asthma (21% vs
      5%; P = .002), food sensitization (47% vs 13%; P < .001), and eczema (66% vs 43%;
      P = .01) and increased total IgE (155 kU/L vs 41 kU/L; P < .001), blood
      eosinophil count (0.46 x 10(9)/L vs 0.30 x 10(9)/L; P = .01), FeNO (15.9 ppb vs
      6.6 ppb; P < .001), and bronchial hyperresponsiveness (23% vs 9%; P = .008).
      Filaggrin null-mutations were associated with allergic rhinitis (odds ratio, 3.3;
      95% CI, 1.3-8.3) but did not modify these associations. Children with nonallergic
      rhinitis also had increased asthma prevalence (20% vs 5%; P = .001) but showed no
      association with filaggrin null-mutations, eczema, food sensitization, total IgE,
      blood eosinophil count, FeNO, or bronchial responsiveness. CONCLUSION: Asthma is
      similarly associated with allergic and nonallergic rhinitis, suggesting a link
      between upper and lower airways beyond allergy associated inflammation. Only
      children with allergic rhinitis had increased bronchial responsiveness and
      elevated FeNO, suggesting different endotypes of asthma symptoms in young
      children with allergic and nonallergic rhinitis.

PMID- 20816192
TI  - Prediction of the incidence, recurrence, and persistence of atopic dermatitis in
      adolescence: a prospective cohort study.
AB  - BACKGROUND: Although it is known that atopic dermatitis (AD) can develop during
      adolescence, research on its course and predictors in this age group is thus far
      limited. OBJECTIVE: We aimed to describe the course of AD over puberty and
      prospectively determine risk factors for the incidence, recurrence, and
      persistence of AD until adolescence in a population-based cohort study. METHODS:
      German participants of the International Study of Asthma and Allergies in
      Childhood Phase II were followed prospectively. The final dataset comprised 2857
      adolescents, of whom 2433 were unaffected by AD at baseline. Bivariate and
      multivariate prediction models for the incidence, recurrence, and persistence of
      AD using early-life factors, family history of atopic diseases, and job history
      as predictors were developed. RESULTS: The incidence of AD between ages 9 to 11
      and 16 to 20 years was 1.7%, and recurrence was 2.4%. AD persisted in 47.6% of
      adolescents with AD symptoms at baseline (n = 424). High socioeconomic status,
      female sex, asthma symptoms and a positive skin prick test response at baseline,
      parental history of rhinitis/AD, and having worked in a high-risk job were
      significant predictors for the course of disease. With all the factors present,
      the probability of the incidence of AD was 21.4% (95% CI, 1.8% to 80.2%) and
      increased up to 81.7% (95% CI, 47.0% to 95.8%) for recurrence of AD and 87.6%
      (95% CI, 63.4% to 96.6%) for persistence of AD among those affected by AD. Early
      life exposures did not predict the course of AD over puberty. CONCLUSION: Genetic
      factors, early allergen sensitization, and having worked in a high-risk job seem
      to be more important for disease development in late adolescence than other early
      life exposures.

PMID- 20816189
TI  - Urinary leukotriene E4/exhaled nitric oxide ratio and montelukast response in
      childhood asthma.
AB  - BACKGROUND: A subset of children with asthma respond better to leukotriene
      receptor antagonists than to inhaled corticosteroids. Information is needed to
      identify children with these preferential responses. OBJECTIVE: We sought to
      determine whether the ratio of urinary leukotriene E(4) (LTE(4)) to fractional
      exhaled nitric oxide (FE(NO)) delineates children with preferential
      responsiveness to montelukast compared with fluticasone propionate (FP) therapy.
      METHODS: Data from 318 children with mild-to-moderate asthma enrolled in 2
      National Heart, Lung, and Blood Institute Childhood Asthma Research and Education
      Network studies (Characterizing the Response to a Leukotriene Receptor Antagonist
      and an Inhaled Corticosteroid [CLIC] and the Pediatric Asthma Controller Trial
      [PACT]) were analyzed. The association between LTE(4)/FE(NO) ratios at baseline
      and improved lung function or asthma control days (ACDs) with montelukast and FP
      therapy was determined, and phenotypic characteristics related to high ratios
      were assessed. RESULTS: LTE(4)/FE(NO) ratios were associated with a greater
      response to montelukast than FP therapy for FEV(1) measurements (2.1% increase
      per doubling of ratio, P = .001) and for ACDs per week (0.3-ACD increase, P =
      .009) in the CLIC study. In PACT the ratio was associated with greater ACD
      responsiveness to MT than FP therapy (0.6 ACD increase, P=.03) [corrected]. In a
      combined study analysis, LTE(4): FE(NO) ratios were associated with greater
      response to MT than FP therapy for FEV(1) (1.8% increase, P =.0005) and ACDs (0.4
      increase, P =.001)[corrected].Children with LTE(4)/FE(NO) ratios at or above the
      75th percentile were likely (P < .05) to be younger and female and exhibit lower
      levels of atopic markers and methacholine reactivity. CONCLUSION: LTE(4)/FE(NO)
      ratios predict a better response to montelukast than FP therapy in children with
      mild-to-moderate asthma.

PMID- 20816193
TI  - Identification of IgE sequential epitopes of lentil (Len c 1) by means of peptide
      microarray immunoassay.
AB  - BACKGROUND: Lentils are often responsible for allergic reactions to legumes in
      Mediterranean children. Although the primary sequence of the major allergen Len c
      1 is known, the location of the IgE-binding epitopes remains undefined.
      OBJECTIVE: We sought to identify IgE-binding epitopes of Len c 1 and relate
      epitope binding to clinical characteristics. METHODS: One hundred thirty-five
      peptides corresponding to the primary sequence of Len c 1 were probed with sera
      from 33 patients with lentil allergy and 15 nonatopic control subjects by means
      of microarray immunoassay. Lentil-specific IgE levels, skin prick test responses,
      and clinical reactions to lentil were determined. Epitopes were defined as
      overlapping signal above interslide and intraslide cutoffs and confirmed by using
      inhibition assays with a peptide from the respective region. Hierarchic
      clustering of microarray data was used to correlate binding patterns with
      clinical findings. RESULTS: The patients with lentil allergy specifically
      recognized IgE-binding epitopes located in the C-terminal region between peptides
      107 and 135. Inhibition experiments confirmed the specificity of IgE binding in
      this region, identifying different epitopes. Linkage of cluster results with
      clinical data and lentil-specific IgE levels displayed a positive correlation
      between lentil-specific IgE levels, epitope recognition, and respiratory
      symptoms. Modeling based on the 3-dimensional structure of a homologous soy
      vicilin suggests that the Len c 1 epitopes identified are exposed on the surface
      of the molecule. CONCLUSION: Several IgE-binding sequential epitopes of Len c 1
      have been identified. Epitopes are located in the C-terminal region and are
      predicted to be exposed on the surface of the protein. Epitope diversity is
      positively correlated with IgE levels, pointing to a more polyclonal IgE
      response.

PMID- 20816194
TI  - Diagnostic approach to the hyper-IgE syndromes: immunologic and clinical key
      findings to differentiate hyper-IgE syndromes from atopic dermatitis.
AB  - BACKGROUND: Hyper-IgE syndromes (HIES) are primary immunodeficiency disorders
      characterized by Staphylococcus aureus abscesses, recurrent pneumonia, increased
      serum IgE levels, and eczema. The association of heterozygous signal transducer
      and activator of transcription 3 (STAT3) mutations with autosomal dominant (AD)
      HIES allows the differentiation of AD-HIES from disorders associated with eczema
      and increased serum IgE levels, such as other primary immunodeficiencies and
      atopic dermatitis. OBJECTIVE: To facilitate early diagnosis of AD-HIES to
      initiate appropriate therapy. METHODS: The clinical phenotype (suggested by a
      National Institutes of Health [NIH] score of >or=40 points), STAT3 genotype, and
      T(H)17 cell counts were compared in a cohort of 78 patients suspected of having
      HIES. RESULTS: Heterozygous STAT3 missense mutations and in-frame deletions were
      identified in 48 patients, all but 2 with an NIH score >or=40 points. Patients
      with STAT3 mutations with HIES showed significantly lower T(H)17 cell counts
      compared with patients with wild-type STAT3 and control subjects. Only 1 patient
      with wild-type STAT3 had both an NIH score >or=40 points and abnormal T(H)17 cell
      counts (<or=0.2% of CD4(+) cells), with this exception being identified with a
      homozygous dedicator of cytogenesis 8 protein (DOCK8) mutation. Pathologic
      shedding of primary teeth was present in 3 patients with wild-type STAT3 and 33
      patients with STAT3 mutations. Internal abscesses and severe infections were
      exclusively seen in patients with STAT3 mutations, who also had increased
      pneumatocele formation and skeletal or connective tissue manifestations compared
      with patients with wild-type STAT3. CONCLUSION: We expanded the number of STAT3
      mutations and validated that the NIH score sensitively identifies patients with
      HIES. Based on our patient cohort, we propose key findings that, when combined
      with T(H)17 cell numbers, predict patients with AD-HIES with STAT3 mutations,
      supporting early diagnosis of AD-HIES.

PMID- 20816196
TI  - Immune mechanisms of sublingual immunotherapy: are oral Langerhans cells the
      masters of tolerance?

PMID- 20816195
TI  - Analyses of shared genetic factors between asthma and obesity in children.
AB  - BACKGROUND: Epidemiologic studies consistently show associations between asthma
      and obesity. Shared genetics might account for this association. OBJECTIVE: We
      sought to identify genetic variants associated with both asthma and obesity.
      METHODS: On the basis of a literature search, we identified genes from (1) genome
      wide association studies (GWASs) of body mass index (BMI; n = 17 genes), (2)
      GWASs of asthma (n = 14), and (3) candidate gene studies of BMI and asthma (n =
      7). We used GWAS data from the Childhood Asthma Management Program to analyze
      associations between single nucleotide polymorphisms (SNPs) in these genes and
      asthma (n = 359 subjects) and BMI (n = 537). RESULTS: One top BMI GWAS SNP from
      the literature, rs10938397 near glucosamine-6-phosphate deaminase 2 (GNPDA2), was
      associated with both BMI (P = 4 x 10(-4)) and asthma (P = .03). Of the top asthma
      GWAS SNPs and the candidate gene SNPs, none was found to be associated with both
      BMI and asthma. Gene-based analyses that included all available SNPs in each gene
      found associations (P < .05) with both phenotypes for several genes: neuronal
      growth regulator 1 (NEGR1); roundabout, axon guidance receptor, homolog 1
      (ROBO1); diacylglycerol kinase, gamma (DGKG); Fas apoptotic inhibitory molecule 2
      (FAIM2); fat mass and obesity associated (FTO); and carbohydrate (N
      acetylgalactosamine 4-0) sulfotransferase 8 (CHST8) among the BMI GWAS genes;
      interleukin 1 receptor-like 1 / interleukin 18 receptor 1 (IL1RL1/IL18R1),
      dipeptidyl-peptidase 10 (DPP10), phosphodiesterase 4D (PDE4D), V-myb
      myeloblastosis viral oncogene homolog (MYB), PDE10A, IL33, and especially protein
      tyrosine phosphatase, receptor type D (PTPRD) among the asthma GWAS genes; and
      protein kinase C, alpha (PRKCA) among the BMI and asthma candidate genes.
      CONCLUSIONS: SNPs within several genes showed associations to BMI and asthma at a
      genetic level, but none of these associations were significant after correction
      for multiple testing. Our analysis of known candidate genes reveals some evidence
      for shared genetics between asthma and obesity, but other shared genetic
      determinants are likely to be identified in novel loci.

PMID- 20816197
TI  - Transfer of maternal IgE can be a common cause of increased IgE levels in cord
      blood.
AB  - BACKGROUND: IgE in cord blood is thought to be a product of the fetus. A high
      level of total IgE is therefore used as a measure of atopic propensity in the
      newborn. We recently found strong evidence that allergen-specific IgE in cord
      blood was the result of transfer of maternal IgE to fetal blood or cord blood
      (maternofetal transfer) rather than fetal production. This also suggests that
      total IgE in cord blood might primarily be a maternal product. OBJECTIVE: We
      sought to determine to what extent increased levels of total IgE in cord blood is
      the result of maternofetal transfer of IgE. METHODS: Total IgE in cord blood was
      analyzed in a prospective birth cohort study. Maternofetal transfer of IgE was
      detected by means of high-sensitivity analyses of cord blood IgA and allergen
      specific IgE and comparison with parental IgE levels and levels at 6 months of
      age. RESULTS: Forty-six percent of cord blood samples with increased IgE levels
      (>or=0.5 IU/mL) showed indication of maternofetal transfer of IgE. Maternal
      origin of IgE in these samples was validated by showing reduced levels of IgE at
      6 months of age compared with samples with no indication of maternofetal transfer
      (geometric mean, 9.4 vs 5.4 IU/mL; P = .01). Maternofetal transfer was not
      appropriately accounted for by the conventional method of cord blood IgA
      measurement. CONCLUSIONS: Maternofetal transfer might be a common cause of
      increased cord blood IgE levels. Future studies should take potential
      maternofetal transfer into account or use other markers of atopy.

PMID- 20816198
TI  - Uncontrolled allergic rhinitis during treatment and its impact on quality of
      life: a cluster randomized trial.

PMID- 20816199
TI  - How adherent to sublingual immunotherapy prescriptions are patients? The
      manufacturers' viewpoint.

PMID- 20816200
TI  - Wheezing in preschool children is associated with increased levels of
      cytokines/chemokines in exhaled breath condensate.

PMID- 20816202
TI  - Auxiliary and autonomous proteoglycan signaling networks.
AB  - Proteoglycans represent a structurally heterogeneous family of proteins that
      typically undergo extensive posttranslational modification with sulfated sugar
      chains. Although historically believed to affect signaling pathways exclusively
      as growth factor coreceptors, proteoglycans are now understood to initiate and
      modulate signal transduction cascades independently of other receptors. From
      within the extracellular matrix, proteoglycans are able to shield protein growth
      factors from circulating proteases and establish gradients that guide cell
      migration. Extracellular proteoglycans are also critical in the maintenance of
      growth factor stores and are thus instrumental in modulating paracrine signaling.
      At the cell membrane, proteoglycans stabilize ligand-receptor interactions,
      creating potentiated ternary signaling complexes that regulate cell
      proliferation, endocytosis, migration, growth factor sensitivity, and matrix
      adhesion. In some cases, proteoglycans are able to independently activate various
      signaling cascades, attenuate the signaling of growth factors, or orchestrate
      multimeric intracellular signaling complexes. Signaling between cells is also
      modulated by proteoglycan activity at the cell membrane, as exemplified by the
      proteoglycan requirement for effective synaptogenesis between neurons. Finally,
      proteoglycans are able to regulate signaling from intracellular compartments,
      particularly in the context of storage granule formation and maintenance. These
      proteoglycans are also major determinants of exocytic vesicle fate and other
      vesicular trafficking pathways. In contrast to the mechanisms underlying
      classical ligand-receptor signaling, proteoglycan signaling is frequently
      characterized by ligand promiscuity and low-affinity binding; likewise, these
      events commonly do not exhibit the same degree of reliance on intermolecular
      structure or charge configurations as other ligand-receptor interactions. Such
      unique features often defy conventional mechanisms of signal transduction, and
      present unique challenges to the study of their indispensable roles within cell
      signaling networks.

PMID- 20816203
TI  - Dual roles of Drosophila glypican Dally-like in Wingless/Wnt signaling and
      distribution.
AB  - Heparan sulfate proteoglycans (HSPGs) are cell-surface and extracellular matrix
      (ECM) macromolecules that comprise a core protein to which heparan sulfate (HS)
      glycosaminoglycan (GAG) chains are attached. Glypican is a major family of HSPGs
      that is linked to the plasma membrane by a glycosylphosphatidylinositol (GPI)
      anchor. Over the past decade, fruit fly Drosophila has been used as a powerful
      model system to examine the functions of HSPGs in cell signaling and development.
      There are two members of Drosophila glypicans named division abnormally delayed
      (Dally) and Dally-like (Dlp). To study the functions of these two glypicans in
      development, we have generated the null mutants of dally and dlp. Here, we
      describe the methods employed to analyze their functions in development with a
      focus on Dlp in the context of Wingless signaling. Our data suggest that Dlp
      shows biphasic activity in Wingless/Wnt signaling and distribution.

PMID- 20816204
TI  - Use of a phage display antibody to measure the enzymatic activity of the Sulfs.
AB  - Sulf-1 and Sulf-2 are extracellular endoglucosamine 6-sulfatases, which
      selectively liberate the 6-O-sulfate groups on glucosamines present in N, 6-O,
      and 2-O trisulfated disaccharides of intact heparan sulfate (HS)/heparin chains.
      The Sulfs are known to regulate signaling of heparin/HS-binding protein ligands,
      such as morphogens and growth factors, presumably through their ability to
      decrease the association between the ligands and HS proteoglycans. These enzymes
      serve important roles in development and are dysregulated in many cancers. We
      previously described arylsulfatase and endoglucosamine 6-sulfatase assays for the
      Sulfs. RB4CD12 is a phage display anti-HS antibody. N-sulfation, 2-O-sulfation,
      and 6-O-sulfation are involved in its binding. In this chapter, we describe the
      application of RB4CD12 in ELISA, flow cytometry, and immunohistochemistry assays
      to measure the enzymatic activity of the Sulfs. These newly established methods
      should facilitate further investigation of the Sulfs in vitro and in vivo.

PMID- 20816205
TI  - Glycomics profiling of heparan sulfate structure and activity.
AB  - The heparan sulfate (HS) family of glycosaminoglycans are highly complex and
      structurally diverse polysaccharides with information encoded within the chains
      that imparts the ability to bind selectively to a wide range of proteins-the "HS
      interactome"-and to regulate their biological activities. However, there are two
      key questions which need to be addressed; first, the extent of structural
      variation of expressed HS structures-the "heparanome"-in specific biological
      contexts and second, the degree of functional selectivity exerted by these
      structures in regulating biological processes. There is a clear need to develop
      more systematic and high throughput approaches in order to address these
      questions. Here, we describe a cohort of protocols for profiling different
      aspects of HS structure and activity, focusing particularly on disaccharide
      building blocks and larger oligosaccharide domains, the latter representing the
      functional units of HS chains. A range of other complementary methods in the
      literature are also discussed. Together these provide a new and more
      comprehensive toolkit to investigate HS structure and activity in a higher
      throughput manner in selected biological systems. The implementation of such a
      glycomics strategy will enable development of a systems biology view of HS
      structure-function relationships and help to resolve the significant puzzle of
      the extensive interactome of HS, which remains a key question in the glycobiology
      field. We anticipate that the next decade will see major advances in our
      understanding of the complex biology of HS.

PMID- 20816206
TI  - Microbe-associated molecular patterns in innate immunity: Extraction and chemical
      analysis of gram-negative bacterial lipopolysaccharides.
AB  - Bacterial lipopolysaccharides (LPSs) are the major component of the outer
      membrane of Gram-negative bacteria. They have a structural role since they
      contribute to the cellular rigidity by increasing the strength of cell wall and
      mediating contacts with the external environment that can induce structural
      changes to allow life in different conditions. Furthermore, the low permeability
      of the outer membrane acts as a barrier to protect bacteria from host-derived
      antimicrobial compounds. They also have a very important role in the elicitation
      of the animal and plant host innate immunity since they are microbe-associated
      molecular patterns, namely, they are glycoconjugates produced only by Gram
      negative bacteria and are recognized as a molecular hallmark of invading
      microbes. LPSs are amphiphilic macromolecules generally comprising three defined
      regions distinguished by their genetics, structures, and function: the lipid A,
      the core oligosaccharide and a polysaccharide portion, the O-chain. In some Gram
      negative bacteria, LPS can terminate with the core portion to form rough-type LPS
      (R-LPS, LOS). In this chapter, we will describe the isolation of both kinds of
      LPSs and their full chemical analysis, pivotal operations in the complete
      description of the primary structure of such important glycoconjugates.

PMID- 20816207
TI  - Structural and functional analysis of glycosphingolipids of Schistosoma mansoni.
AB  - Glycosphingolipids are ubiquitous membrane components that play important roles
      in signal transduction events thereby affecting many cellular functions,
      including modulation of the immune response. Whereas many studies focus on the
      functional roles of glycosphingolipids in mammals, relatively little is known
      about the structures of glycosphingolipids of pathogenic organisms, and how such
      pathogen-derived glycosphingolipids influence immune functions of their hosts.
      Many different glycosphingolipids of the human parasitic helminth Schistosoma
      mansoni have been structurally characterized. Recent evidence indicates that
      glycosphingolipids isolated from different life-cycle stages of the parasite have
      the potential to modulate the function of human dendritic cells, a cell
      population that is crucial to regulate adaptive immunity in the host. A
      remarkable finding in this context is that glycosphingolipids derived from adult
      worms induce maturation of dendritic cells, in contrast to glycosphingolipids of
      eggs or cercariae. The glycosphingolipid-induced dendritic cell activation
      requires intact fucose residues on the glycolipids, and is induced via a
      mechanism that involves both the dendritic cell receptors TLR4 and DC-SIGN. In
      this chapter, we describe methods to extract glycosphingolipids from the
      different life-cycle stages of the parasite, techniques to separate them by thin
      layer chromatography or high-performance liquid chromatography as well as
      strategies to structurally characterize the glycan and ceramide moieties of the
      glycosphingolipids. Moreover, an overview is provided of the structural diversity
      in the glycosphingolipid-derived glycan moieties found in this helminth. Finally,
      we discuss methods used to isolate monocyte-derived dendritic cells from human
      blood and to study the modulation of dendritic cell function by these molecules.

PMID- 20816208
TI  - Biotoxicity assays for fruiting body lectins and other cytoplasmic proteins.
AB  - Recent studies suggest that a specific class of fungal lectins, commonly referred
      to as fruiting body lectins, play a role as effector molecules in the defense of
      fungi against predators and parasites. Hallmarks of these fungal lectins are
      their specific expression in reproductive structures, fruiting bodies, and/or
      sclerotia and their synthesis on free ribosomes in the cytoplasm. Fruiting body
      lectins are released upon damage of the fungal cell and bind to specific
      carbohydrate structures of predators and parasites, which leads to deterrence,
      inhibition of growth, and development or even killing of these organisms. Here,
      we describe assays to assess the toxicity of such lectins and other cytoplasmic
      proteins toward three different model organisms: the insect Aedes aegypti, the
      nematode Caenorhabditis elegans, and the amoeba Acanthamoeba castellanii. All
      three assays are based on heterologous expression of the examined proteins in the
      cytoplasm of Escherichia coli and feeding of these recombinant bacteria to
      omnivorous and bacterivorous organisms.

PMID- 20816209
TI  - Carbohydrate signaling by C-type lectin DC-SIGN affects NF-kappaB activity.
AB  - Pathogen recognition is central to the induction of adaptive immunity. Dendritic
      cells (DCs) express different pattern recognition receptors (PRRs), such as Toll
      like receptors and C-type lectins, that sense invading pathogens. Pathogens
      trigger a specific set of PRRs, leading to activation of intracellular signaling
      processes that shapes the adaptive immunity. It is becoming clear that cross talk
      between these signaling routes is crucial for pathogen-tailored immune responses.
      The C-type lectin DC-SIGN interacts with different mannose-expressing pathogens
      such as Mycobacterium tuberculosis and HIV-1. Notably, DC-SIGN triggering by
      these pathogens results in a specific Raf-1-dependent signaling pathway that
      modulates TLR-induced NF-kappaB activation. Here, we will discuss the various
      methods that we have used to identify the innate signaling by the C-type lectin
      DC-SIGN, and how to analyze the consequences on NF-kappaB activation.

PMID- 20816210
TI  - Engineered carbohydrate-recognition domains for glycoproteomic analysis of cell
      surface glycosylation and ligands for glycan-binding receptors.
AB  - Modular calcium-dependent carbohydrate-recognition domains (CRDs) of mammalian
      glycan-binding receptors (C-type lectins), engineered to have novel glycan
      binding selectivity, have been developed as tools for the study of glycans on
      cell surfaces. Structure-based specificity swapping between domains can be
      complemented by empirical characterization of ligand-binding specificity using
      glycan arrays. Both natural and modified CRDs can be used as probes for detecting
      and isolating glycoproteins that bear specific glycan epitopes and that act as
      target ligands for glycan-binding receptors. CRD-based affinity chromatography
      facilitates proteomic and glycomic analysis of such ligands.

PMID- 20816211
TI  - Mannose 6-phosphate receptor homology domain-containing lectins in mammalian
      endoplasmic reticulum-associated degradation.
AB  - Quality control of glycoproteins synthesized in the endoplasmic reticulum (ER) is
      mediated by lectins and molecular chaperones. N-linked Glc(3)Man(9)GlcNAc(2)
      oligosaccharides attached to the nascent polypeptides are processed and
      recognized by lectins in the ER. OS-9 and XTP3-B/Erlectin, mannose 6-phosphate
      receptor homology (MRH) domain-containing lectins in mammals, were recently
      identified as ER luminal glycoproteins that participate in ER-associated
      degradation (ERAD) of misfolded proteins. Frontal affinity chromatography (FAC)
      and cell-surface expressed lectin assay revealed that both OS-9 and XTP3-B
      recognize high-mannose type N-glycans that lack the terminal mannose on the C
      branch. Furthermore, these lectins associate with the HRD1-SEL1L ubiquitin ligase
      complex on the ER membrane. In this chapter, we describe the FAC methods used to
      analyze the carbohydrate-recognition specificity of OS-9 and methods to examine
      the interaction and the effect on ERAD of these proteins in vivo. We also discuss
      the structure and function of OS-9 and XTP3-B, and the effect of these lectins on
      ERAD.

PMID- 20816212
TI  - Multiple functional targets of the immunoregulatory activity of galectin-1:
      Control of immune cell trafficking, dendritic cell physiology, and T-cell fate.
AB  - In the postgenomic era, the study of the glycome-the whole repertoire of
      saccharides in cells and tissues-has enabled the association of unique glycan
      structures with specific physiological and pathological processes. The
      responsibility for deciphering this biological information belongs to endogenous
      glycan-binding proteins or lectins. Galectin-1, a prototypic member of a family
      of structurally related proteins, has demonstrated selective antiinflammatory and
      immunoregulatory effects either by controlling immune cell trafficking, "fine
      tuning" dendritic cell physiology and regulating T-cell fate. These regulatory
      functions mediated by an endogenous glycan-binding protein may contribute to
      fulfill the needs for immune cell homeostasis, including preservation of
      fetomaternal tolerance and prevention of collateral damage as a result of
      microbial invasion or autoimmune pathology. We will discuss here the conceptual
      framework which led to the study of galectin-glycan lattices as a novel paradigm
      of immune cell communication in physiological and pathological processes and will
      highlight selected methods and experimental strategies which have contributed to
      the study of the immunoregulatory activities of this multifaceted glycan-binding
      protein both in in vitro and in vivo biological settings.

PMID- 20816213
TI  - Manipulating cell surface glycoproteins by targeting N-glycan-galectin
      interactions.
AB  - The interaction of cell surface receptors and transporters with cognate ligands
      depends on their concentration, distribution, and organization at the cellular
      surface. The majority of cell surface receptors and transporters are co- and/or
      post-translationally modified with asparagine (N)-linked oligosaccharides
      (glycans). N-Glycan number and structure combine to control the concentration of
      glycoproteins at the cell surface through interactions with endogenous lectins
      such as galectins. ER/Golgi enzyme activity and hexosamine pathway supply of
      Golgi metabolites co-dependently regulate N-glycan biosynthesis and combine to
      provide adaptive control over cell growth and differentiation. Studies in mice
      and humans have revealed metabolic and genetic dysregulation of N-glycosylation
      in T-cell-mediated autoimmunity. In this chapter, we describe methods used to
      analyze N-glycan-galectin interactions in controlling the distribution and
      organization of cell surface receptors and transporters.

PMID- 20816214
TI  - Galectin-1 and HIV-1 Infection.
AB  - Initial binding of human immunodeficiency virus-1 (HIV-1) to its susceptible
      CD4(+) cells is the limiting step for the establishment of infection as the
      avidity of viral envelope gp120 for CD4 is not high and the number of viral
      envelope spikes on the surface is found to be low compared to highly infectious
      viruses. Several host factors, such as C-type lectins, are listed as being able
      to enforce or facilitate the crucial interaction of HIV-1 to the susceptible
      cell. Recent works suggest that a host soluble beta-galactoside-binding lectin,
      galectin-1, also facilitates both virion binding and the infection of target
      cells in a manner dependent on lactose but not mannose, suggesting that this
      soluble galectin can be considered as a host factor that influences HIV-1
      pathogenesis. In this chapter, we describe methods used to investigate the
      potential role of the galectin family in HIV-1-mediated disease progression.

PMID- 20816215
TI  - The glycomics of glycan glucuronylation in Drosophila melanogaster.
AB  - As glycan characterization methods increase in sensitivity, new opportunities
      arise to undertake glycomic analyses on limiting amounts of material. Developing
      systems present special challenges since the amount of available tissue can
      restrict deep glycan characterization. We have optimized mass spectrometric
      methods with the goal of obtaining full glycan profiles from small amounts of
      tissue derived from organisms of particular interest. A major target of our
      efforts has been the Drosophila embryo, allowing us to leverage the tools already
      developed in this organism to meld glycomics, genomics, and molecular genetics.
      Our analysis of the N-linked, O-linked (non-GAG), and glycosphingolipid (GSL)
      glycans of the Drosophila embryo have identified expected and unexpected glycan
      structures. We have verified previous findings regarding the predominance of high
      Man and pauci-Man N-linked glycans, but have also detected minor families of
      sialylated and glucuronylated N-linked structures. Glucuronic acid (GlcA) also
      presents itself as an abundant modification of O-linked and GSL glycans. We
      describe critical advancements in our methodology and present the broad range of
      contexts in which GlcA is found in the Drosophila embryo.

PMID- 20816216
TI  - Glycosyltransferases and transporters that contribute to proteoglycan synthesis
      in Drosophila: Identification and functional analyses using the heritable and
      inducible RNAi system.
AB  - Drosophila melanogaster is an important model organism that can be used as a
      powerful genetic tool to analyze the physiological functions of various
      molecules. Recently, many successful analyses of the function of glycans in vivo
      have been performed using Drosophila. The glycan portion of proteoglycans, namely
      glycosaminoglycans (GAGs), which include heparan sulfate (HS) and chondroitin
      sulfate (CS), is conserved structurally between Drosophila and mammals, including
      humans. The analysis of mutant and RNAi flies has demonstrated that HS
      proteoglycans play key roles in the regulation of various basic developmental
      signaling pathways, including those of fibroblast growth factor (FGF), Wingless
      (Wg)/Wnt, Hedgehog (Hh), and Decapentaplegic (Dpp, a BMP-type ligand that belongs
      to the TGFbeta family). In this chapter, I give an overview of glycosaminoglycan
      biosynthesis in Drosophila and then describe the methods that can be used to
      identify and perform functional analyses of the molecules involved in this
      process, namely glycosyltransferases, sulfotransferases, sugar-nucleotide
      transporters including PAPS transporters, and core proteins, using the heritable
      and inducible RNAi system.

PMID- 20816217
TI  - O-GlcNAc modification of the extracellular domain of Notch receptors.
AB  - Epidermal growth factor (EGF) domains are posttranslationally modified with
      unique O-linked glycans. The classical types of O-glycans on EGF domains are O
      fucose and O-glucose glycans, found on many plasma glycoproteins and signaling
      molecules, whose biological functions have been demonstrated especially in the
      context of the Notch signaling pathway. We recently discovered O-GlcNAc
      modification as a new modification of the EGF domain that occurs on the conserved
      Ser/Thr residue located between the fifth and sixth cysteine residues within the
      EGF domain of Notch receptors in Drosophila. Here, we describe the methods
      employed to detect the O-GlcNAc modification of EGF repeats of Notch receptors.
      These methods include mass spectrometric analysis, galactosyltransferase
      labeling, immunoblotting with a specific antibody, and beta-N-acetyl
      hexosaminidase digestion experiments. We also describe a method to detect O
      GlcNAc transferase activity from crude membrane fraction proteins prepared from
      cultured S2 cells.

PMID- 20816218
TI  - Regulation of notch signaling via O-glucosylation insights from Drosophila
      studies.
AB  - Recent work using Drosophila melanogaster has shown that a protein O
      glucosyltransferase called Rumi regulates Notch signaling. Studies on several
      alleles of rumi identified in a forward genetic screen indicated that Rumi is a
      temperature-sensitive regulator of Notch signaling in flies. Further genetic and
      rescue experiments demonstrated that Rumi is a general regulator of Drosophila
      Notch signaling. Biochemical analyses showed that Rumi adds glucose to specific
      EGF repeats in the extracellular domain of Notch receptor in the Drosophila S2
      cell line. Furthermore, RNAi-mediated knockdown of Rumi in this cell line
      resulted in a severe decrease in the level of O-linked glucose on Notch. In this
      chapter, we discuss the genetic and biochemical methods used to determine the
      role of Rumi in the regulation of Notch signaling in flies.

PMID- 20816219
TI  - O-fucosylation of thrombospondin type 1 repeats.
AB  - Thrombospondin type 1 repeats (TSRs) are small cysteine-rich motifs with three
      conserved disulfide bonds originally described as modules in the thrombospondins.
      Since then, TSRs have been found as tandem repeats in a wide variety of secreted
      and cell-surface proteins of diverse function. TSRs in many contexts are known to
      bind a variety of receptors and have antiangiogenic capabilities. They can be
      modified with O-linked fucose on serine/threonine found in the consensus, CX(2
      3)(S/T)CX(2)G. Here we review what is known about O-fucosylation of TSRs and
      describe in detail mass spectral methods to map sites of O-fucosylation on
      proteins containing TSRs. These methods include techniques to identify
      glycosylated peptides and the relative amounts of elongated products by
      electrospray ionization mass spectrometry of glycopeptides.

PMID- 20816220
TI  - Use of glycan microarrays to explore specificity of glycan-binding proteins.
AB  - Microarrays of defined glycans represent a high throughput approach to
      determining the specificity of lectins, or more generally glycan-binding proteins
      (GBPs). The utility of a glycan microarray is directly related to the number and
      variety of the glycans available on the printed surface for interrogation by
      GBPs. The Consortium for Functional Glycomics (CFG), funded by the National
      Institute of General Medical Sciences (NIGMS), has generated a glycan microarray
      available to the public as an investigator-driven resource, where hundreds of
      GBPs have been analyzed. Here we describe the methods generally used by the CFG
      to prepare glycan arrays and interrogate them with GBPs. We also describe our new
      approach to normalizing glycan microarray data derived from concentration
      dependent analyses of GBP binding, and the application of this approach with the
      plant lectin Sambucus nigra agglutinin (SNA-I) and human galectin-8. The use of
      glycan microarrays with this approach readily generates a prediction of the
      glycan determinants required for high affinity binding by a GBP.

PMID- 20816221
TI  - Functional roles of the bisecting GlcNAc in integrin-mediated cell adhesion.
AB  - N-acetylglucosaminyltransferase III (GnT-III) transfers N-acetylglucosamine
      (GlcNAc) from UDP-GlcNAc to core mannose with a beta1,4 linkage, so-called
      bisecting GlcNAc, in N-glycans. The bisecting GlcNAc is found in various hybrid
      and complex N-glycans. GnT-III is generally regarded as a key glycosyltransferase
      in N-glycan biosynthetic pathways. Introduction of a bisecting GlcNAc suppresses
      further processing and elongation of N-glycans catalyzed by other GlcNAc
      transferases to form branching structures, such as N
      acetylglucosaminyltransferase V (GnT-V), since GnT-V cannot utilize the bisected
      oligosaccharide as a substrate. Considering that expression of the enzyme leads
      to a remarkable structural alteration of the N-glycans on cell surface, it has
      been postulated that the enzyme is associated with various biological events such
      as cell adhesion, migration, cell growth, cell differentiation, and tumor
      invasion. Integrin is a major carrier of N-glycans. In fact, overexpression of
      GnT-III reduced the beta1,6 GlcNAc branching structures, in conjunction with the
      increase in the bisected N-glycans on integrins, and resulted in an inhibition of
      integrin-mediated cell spreading and migration, and the cellular phosphorylation
      levels. Conversely, knockdown of endogenous GnT-III expression resulted in
      increased cell migration, concomitant with an increase in beta1,6 GlcNAc-branched
      N-glycans on integrins. Thus, N-glycan could be considered as either a positive
      or negative regulator for biological functions of integrin.

PMID- 20816222
TI  - Lectin-based glycoproteomic techniques for the enrichment and identification of
      potential biomarkers.
AB  - Glycan structures on glycoproteins are controlled by several factors such as
      regulated expression of glycosyltransferases and glycosylhydrolases, as well as
      regulation of glycoprotein expression, folding, and transport through the ER and
      Golgi. In cancer, for example, the glycosylation of glycoproteins can be
      significantly altered due to changes in the expression levels of
      glycosyltransferases as a result of oncogene activated signaling pathways coupled
      with gain or loss in chromosome copy number. Cumulatively these changes result in
      glycoproteins exported to the cell surface and extracellular region with altered
      glycan structures that can lead to significant changes in cell phenotype.
      Therefore, it is advantageous to be able to capture and identify proteins that
      express particular glycans or classes of glycans. In this report, we discuss
      extraction methods and lectin capture methodology that can be used to enrich and
      identify by mass spectrometry glycoproteins that express specific glycans that
      change in response to disorders or diseases, such as the presence of
      malignancies.

PMID- 20816223
TI  - High-throughput RNAi screening for N-glycosylation dependent loci in
      Caenorhabditis elegans.
AB  - The attachment of oligosaccharides to the amide nitrogen of asparagine side
      chains on proteins is a fundamental process occurring in all metazoans. This
      process, known as N-glycosylation, is complex and is achieved by the precise
      interactions of various cellular components. The initial stage of N-glycan
      biosynthesis is preserved among eukaryotes, and defective enzymes or components
      in this pathway cause congenital disorders of glycosylation type I (CDG-I) in
      humans. This disease is rare but exceedingly life-threatening with no known cure.
      Paramount to CDG treatment and care is understanding the mechanisms of N
      glycosylation and factors that influence the pathology of the disease, both of
      which are not completely known. Here we outline a novel technique to model a CDG
      I-like condition and identify genes that are vital for healthy glycosylation in
      Caenorhabditis elegans. C. elegans is a well-established model for understanding
      the complexity of glycosylation in development and disease. Although C. elegans N
      glycan structures are dissimilar to that observed in higher eukaryotes, they
      contain over 150 gene homologs that are directly involved in glycosylation.
      Moreover, the annotated genome of C. elegans, its susceptibility to genetic
      silencing and its recognizable phenotypes, is a suitable model to dissect the
      complex phenomenon of glycosylation and identify genes that are required for N
      glycan biosynthesis.

PMID- 20816224
TI  - The acidic environment of the Golgi is critical for glycosylation and transport.
AB  - Proteins and glycolipids are modified by various modes of glycosylation in the
      endoplasmic reticulum (ER) and the Golgi apparatus. It is well known that the
      lumen of the Golgi is acidic and compromising acidification by chemical compounds
      causes impaired glycosylation and transport of proteins (Axelsson et al., 2001;
      Chapman and Munro, 1994; Palokangas et al., 1994; Presley et al., 1997; Puri et
      al., 2002; Reaves and Banting, 1994; Rivinoja et al., 2006; Tartakoff et al.,
      1978). The mechanisms by which glycosylation and transport are regulated by an
      acidic pH remain largely unknown. Recent findings that the impaired regulation of
      an acidic environment may be implicated in the pathology of several diseases
      emphasize the importance of pH regulation (Jentsch, 2007; Kasper et al., 2005;
      Kornak et al., 2001; Kornak et al., 2008; Piwon et al., 2000; Stobrawa et al.,
      2001; Teichgraber et al., 2008). We recently established a mutant cell line in
      which Golgi acidification was selectively impaired and the raised luminal Golgi
      pH caused impaired transport and glycosylation of proteins and altered Golgi
      morphology (Maeda et al., 2008). As alkalinizing compounds nonselectively affect
      all acidic organelles including lysosomes, endosomes, and the Golgi, the mutant
      cell is thought to be useful in analyzing how the acidic environment of the Golgi
      regulates glycosylation. In this chapter, we have introduced how we established
      mutant cells with impaired Golgi acidification and methods for measuring Golgi
      pH.

PMID- 20816225
TI  - Enzymatic synthesis of lacto-N-difucohexaose I which binds to Helicobacter
      pylori.
AB  - Helicobacter pylori is known to bind with sugar chains possessing Lewis b
      structure. We are trying to combine oligosaccharides containing Lewis b sugar
      chain to water insoluble polysaccharide through some linker. Lacto-N
      difucohexaose I (LNDFH I; Fucalpha1-->2Galbeta1-->3[Fucalpha1-->4]GlcNAcbeta1-
      >3Galbeta1-->4Glc) fits for that purpose, since it consists of Lewis b
      tetrasaccharide and lactose whose d-glucose residue can be utilized as a linker.
      We thus developed a method to synthesize this hexaose enzymatically. First, beta
      1,3-N-acetylglucosaminyltransferase (beta-1,3-GnT) was partially purified from
      bovine blood by an established method. Using this enzyme preparation, d-GlcNAc
      was attached to the d-galactose residue of lactose with a beta-1,3-linkage to
      produce lacto-N-triose II at 44% yield. The low yield was thought to be due to
      contaminating N-acetylglucosaminidase that would have hydrolyzed the product,
      lacto-N-triose II. Next, d-galactose was attached by transglycosylation using
      ortho-nitrophenyl beta-d-galactopyranoside as a donor with the aid of recombinant
      beta-1,3-galactosidase from Bacillus circulans to generate lacto-N-tetraose (LNT)
      at 22% yield. l-Fucose was then linked to the d-galactose residue of LNT via an
      alpha-1,2-linkage using recombinant human fucosyltransferase I (FUT1) expressed
      in a baculovirus system (71% yield). The obtained pentasaccharide was
      subsequently incubated with GDP-beta-l-fucose and commercial fucosyltransferase
      III (FUT3) to attach l-fucose to the d-GlcNAc residue of LNT with an alpha-1,4
      linkage. After purification with an activated carbon column chromatography, 1.7
      mg of LNDFH I was obtained (85% yield). We thus produced LNDFH I over four
      enzymatic steps with a yield of 6%.

PMID- 20816226
TI  - The Drosophila 7-pass transmembrane glycoprotein BOSS and metabolic regulation:
      What Drosophila can teach us about human energy metabolism.
AB  - Glucose is a key carbohydrate for the majority of living organisms. In animals,
      plasma glucose levels must be strictly regulated and maintained at proper levels.
      Abnormal upregulated glucose levels lead to various human metabolic disorders
      such as diabetes or obesity. In the diabetic state, protein glycation occurs,
      producing nonenzymatic products that are thought to be causative compounds for
      the disease. During evolution, animals developed sensing and regulatory
      mechanisms to maintain constant levels of body glucose levels. How organisms
      respond to extracellular glucose and how glucose controls nutrient homeostasis,
      however, have remained uncertain. Recently, we identified bride of sevenless
      (BOSS) in Drosophila as a glucose-responding membrane receptor. In this chapter,
      we summarize the utility of Drosophila as a model organism for studying conserved
      mechanisms of glucose and triacylglycerol (energy) homeostatic metabolism through
      the 7-pass transmembrane glycoprotein BOSS, which carries N-linked carbohydrates.

PMID- 20816227
TI  - Nuclear mechanics and genome regulation.

PMID- 20816228
TI  - Fluorescence fluctuation microscopy to reveal 3D architecture and function in the
      cell nucleus.
AB  - The three-dimensional (3D) architecture of the cell nucleus is determined not
      only by the presence of subnuclear domains, such as the nuclear envelope,
      chromosome territories, and nuclear bodies, but also by smaller domains which
      form in response to specific functions, such as RNA transcription, DNA
      replication, and DNA repair. Since both stable and dynamic structures contribute
      to nuclear morphology, it is important to study the biophysical principles of the
      formation of macromolecular assemblies within the nucleus. For this purpose, a
      variety of fluorescence fluctuation microscopy techniques can be applied. Here,
      we summarize our current knowledge on the 3D architecture of the mammalian cell
      nucleus and describe in detail how the assembly of functional nuclear protein
      complexes can be analyzed in living cells using fluorescence bleaching
      techniques, fluorescence correlation spectroscopy, raster image correlation
      spectroscopy, and mathematical modeling. In conclusion, the application of all
      these techniques in combination is a powerful tool to assess the full spectrum of
      nuclear protein dynamics and to understand the biophysical principles underlying
      nuclear structure and function.

PMID- 20816229
TI  - Studying histone modifications and their genomic functions by employing chromatin
      immunoprecipitation and immunoblotting.
AB  - Histones are one of the most abundant and highly conserved proteins in
      eukaryotes. Apart from serving as structural entities for orderly compaction of
      genomes, they play an instrumental role in the regulation of many important
      biological processes involving DNA such as transcription, DNA repair, and the
      cell cycle. Histone modifications have been implicated in maintaining the
      transcriptionally poised state of important genesin embryonic stem cells. Histone
      modifications are believed to be responsible for compartmentalization of
      chromatin into active and inactive domains. Hence, the tools and techniques
      required for studying these proteins are of utmost importance to biologists. This
      chapter provides a brief review of the posttranslational modifications of the N
      terminal tails of histones and their biological roles, followed by step-by-step
      protocols for the most common techniques employed to study them. Here, we
      describe chromatin immunoprecipitation (ChIP) for studying the genomic functions
      of the most widely studied histone modifications, namely, histone H3 lysine 9
      acetylation and histone H3 lysine 9 trimethylation that are typically associated
      with transcriptional activation and repression, respectively. Special emphasis
      has been given on the method of preparation of sonicated chromatin prior to
      immunoprecipitation since this single step affects the success of ChIP greatly
      and is often poorly described in published protocols. Protocol for histone
      isolation by acid-extraction and detection by Coomassie staining has also been
      described. We also describe the protocol for immunoblot analysis of histones
      using antibodies against key histone modifications. This chapter will serve as a
      useful resource in the study of histones and their posttranslational
      modifications.

PMID- 20816230
TI  - Dynamic organization of chromatin assembly and transcription factories in living
      cells.
AB  - The interphase nucleus is an active organelle involved in processing genetic
      information. In higher order eukaryotes, information control is compartmentalized
      - for example at the scale of inter-chromosome territories and nuclear bodies.
      Regulatory proteins, nuclear bodies and chromatin assembly are found to be highly
      dynamic within the nucleus of primary cells and through cellular differentiation
      programs. In this chapter we describe live-cell fluorescence based techniques and
      single particle tracking analysis, to probe the spatio-temporal dimension in
      nuclear function.

PMID- 20816231
TI  - Manipulation and isolation of single cells and nuclei.
AB  - The heterogeneous behavior of cells within a cell population makes measurements
      at the multicellular level insensitive to changes in single cells. Single-cell
      and single-nucleus analyses are therefore important to address this deficiency
      which will aid in the understanding of fundamental biology at both the cellular
      and subcellular levels. Recent technological advancements have enabled the
      development of new methodologies capable of handling these new challenges. This
      review highlights various techniques used in single-cell and single-nucleus
      manipulation and isolation. In particular, the applications related to
      microfluidics, electrical, optical, and physical methods will be discussed.
      Ultimately, it is hoped that these techniques will enable fundamental tests to be
      conducted on single cells and nuclei. One important potential outcome is that
      this will contribute not only towards detection and isolation of diseased cells
      but also more accurate diagnosis and prognosis of human diseases.

PMID- 20816233
TI  - Altered mechanical properties of the nucleus in disease.
AB  - In eukaryotic cells, the nucleus is the largest and most rigid organelle.
      Therefore, its physical properties contribute critically to the biomechanical
      behavior of cells, e.g., during amoeboid migration or perfusion through narrow
      capillaries. Furthermore, it has been speculated that nuclear deformations could
      directly allow cells to sense mechanical stress, e.g., by modulating the access
      of specific transcription factors to their binding sites. Defects in nuclear
      mechanics have also been reported in a variety of muscular dystrophies caused by
      mutations in nuclear envelope proteins, indicating an important role in the
      maintenance of cells in mechanically stressed tissue. These findings have
      prompted the growing field of nuclear mechanics to develop advanced experimental
      methods to study the physical properties of the nucleus as a function of nuclear
      structure and organization, and to understand its role in physiology and disease.
      These experimental techniques include micropipette aspiration, atomic force
      microscopy of isolated nuclei, cellular strain and compression experiments, and
      microneedle manipulation of intact cells. These experiments have provided
      important insights into the mechanical behavior of the nucleus under
      physiological conditions, the distinct mechanical contributions of the nuclear
      lamina and interior, and how mutations in nuclear envelope proteins associated
      with a variety of human diseases can cause distinct alterations in the physical
      properties of the nucleus and contribute to the disease mechanism. Here, we
      provide a brief overview of the most common experimental techniques and their
      application and discuss the implication of their results on our current
      understanding of nuclear mechanics.

PMID- 20816232
TI  - Beyond lamins other structural components of the nucleoskeleton.
AB  - The nucleus is bordered by a double bilayer nuclear envelope, communicates with
      the cytoplasm via embedded nuclear pore complexes, and is structurally supported
      by an underlying nucleoskeleton. The nucleoskeleton includes nuclear intermediate
      filaments formed by lamin proteins, which provide major structural and mechanical
      support to the nucleus. However, other structural proteins also contribute to the
      function of the nucleoskeleton and help connect it to the cytoskeleton. This
      chapter reviews nucleoskeletal components beyond lamins and summarizes specific
      methods and strategies useful for analyzing nuclear structural proteins including
      actin, spectrin, titin, linker of nucleoskeleton and cytoskeleton (LINC) complex
      proteins, and nuclear spindle matrix proteins. These components can localize to
      highly specific functional subdomains at the nuclear envelope or nuclear interior
      and can interact either stably or dynamically with a variety of partners. These
      components confer upon the nucleoskeleton a functional diversity and mechanical
      resilience that appears to rival the cytoskeleton. To facilitate the exploration
      of this understudied area of biology, we summarize methods useful for localizing,
      solubilizing, and immunoprecipitating nuclear structural proteins, and a state-of
      the-art method to measure a newly-recognized mechanical property of nucleus.

PMID- 20816234
TI  - Theoretical concepts and models of cellular mechanosensing.
AB  - Recent discoveries have established that mechanical properties of the cellular
      environment such as its rigidity, geometry, and external stresses play an
      important role in determining the cellular function and fate. Mechanical
      properties have been shown to influence cell shape and orientation, regulate cell
      proliferation and differentiation, and even govern the development and
      organization of tissues. In recent years, many theoretical and experimental
      investigations have been carried out to elucidate the mechanisms and consequences
      of the mechanosensitivity of cells. In this review, we discuss recent theoretical
      concepts and approaches that explain and predict cell mechanosensitivity. We
      focus on the interplay of active and passive processes that govern cell-cell and
      cell-matrix interactions and discuss the role of this interplay in the processes
      of cell adhesion, regulation of cytoskeleton mechanics and the response of cells
      to applied mechanical stresses.

PMID- 20816235
TI  - Mechanical induction of gene expression in connective tissue cells.
AB  - The extracellular matrices of mammals undergo coordinated synthesis and
      degradation, dynamic remodeling processes that enable tissue adaptations to a
      broad range of environmental factors, including applied mechanical forces. The
      soft and mineralized connective tissues of mammals also exhibit a wide repertoire
      of mechanical properties, which enable their tissue-specific functions and
      modulate cellular responses to forces. The expression of genes in response to
      applied forces are important for maintaining the support, attachment, and
      function of various organs including kidney, heart, liver, lung, joint, and
      periodontium. Several high-prevalence diseases of extracellular matrices
      including arthritis, heart failure, and periodontal diseases involve pathological
      levels of mechanical forces that impact the gene expression repertoires and
      function of bone, cartilage, and soft connective tissues. Recent work on the
      application of mechanical forces to cultured connective tissue cells and various
      in vivo force models have enabled study of the regulatory networks that control
      mechanically induced gene expression in connective tissue cells. In addition to
      the influence of mechanical forces on the expression of type 1 collagen, which is
      the most abundant protein of mammals, new work has shown that the expression of a
      wide range of matrix, signaling, and cytoskeletal proteins are regulated by
      exogenous mechanical forces and by the forces generated by cells themselves. In
      this chapter, we first discuss the fundamental nature of the extracellular matrix
      in health and the impact of mechanical forces. Next we consider the utilization
      of several, widely employed model systems for mechanical stimulation of cells.
      Finally, we consider in detail how application of tensile forces to cultured
      cardiac fibroblasts can be used for the characterization of the signaling systems
      by which mechanical forces regulate myofibroblast differentiation that is seen in
      cardiac pressure overload.

PMID- 20816236
TI  - Physical plasticity of the nucleus and its manipulation.
AB  - The genome is virtually identical in all cells within an organism, with
      epigenetic changes contributing largely to the plasticity in gene expression
      during both development and aging. These changes include covalent modifications
      of chromatin components and altered chromatin organization as well as changes in
      other nuclear components, such as nuclear envelope lamins. Given that DNA in each
      chromosome is centimeters long and dozens of chromosomes are compacted into a
      microns-diameter nucleus through non-trivial interactions with the bounding
      envelope, the polymer physics of such a structure under stress can be complex but
      perhaps systematic. We summarize micromanipulation methods for measuring the
      physical plasticity of the nucleus, with recent studies documenting the extreme
      flexibility of human embryonic stem cells and the rigidification in model aging
      of progerin-type nuclei. Lamin-A/C is a common molecular factor, and methods are
      presented for its knockdown and measurement.

PMID- 20816237
TI  - Prestressed nuclear organization in living cells.
AB  - The nucleus is maintained in a prestressed state within eukaryotic cells,
      stabilized mechanically by chromatin structure and other nuclear components on
      its inside, and cytoskeletal components on its outside. Nuclear architecture is
      emerging to be critical to the governance of chromatin assembly, regulation of
      genome function and cellular homeostasis. Elucidating the prestressed
      organization of the nucleus is thus important to understand how the nuclear
      architecture impinges on its function. In this chapter, various chemical and
      mechanical methods have been described to probe the prestressed organization of
      the nucleus.

PMID- 20816238
TI  - Nanotopography/mechanical induction of stem-cell differentiation.
AB  - The interplay of biophysical and biochemical cues in the extracellular
      microenvironment regulate and control the cell fate of stem cells. Understanding
      the interaction between stem cells and the extracellular substrate will be
      crucial in controlling stem cell differentiation for regenerative medicine
      applications. One of the biophysical properties of the microenvironment is
      substrate topology, which has been demonstrated to be an important mediator of
      stem cell lineage regulation. Biomimetic microenvironment topology can be
      engineered by chemical patterning or physical patterning. The rapid advancements
      in nanofabrication techniques have enabled versatility in patterning types with
      controlled chemistries, geometries and sizes. The chapter will focus on
      discussing the effect on physical nanotopography on stem cell differentiation and
      the current theories on the topography/ mechanical force induction of stem cell
      differentiation possibly through integrin clustering, focal adhesion,
      cytoskeleton organization and the nuclear mechanosensing to sense and integrate
      these biophysical signals from the extracellular microenvironment.

PMID- 20816239
TI  - Mechanical induction in embryonic development and tumor growth integrative cues
      through molecular to multicellular interplay and evolutionary perspectives.
AB  - Embryonic development is a coordination of multicellular biochemical patterning
      and morphogenetic movements. Last decades revealed the close control of myosin-II
      dependent biomechanical morphogenesis by patterning gene expression, with
      constant progress in the understanding of the underlying molecular mechanisms.
      Reversed control of developmental gene expression and of myosin-II patterning by
      the mechanical strains developed by morphogenetic movements was recently revealed
      at Drosophila gastrulation, through mechanotransduction processes involving the
      Armadillo/beta-catenin and the downstream of Fog Rho pathways. Here, we present
      the theoretical (simulations integrating the accumulated knowledge in the
      genetics of early embryonic development and morphogenesis) and the experimental
      (genetic and biophysical control of morphogenetic movements) tools having allowed
      the uncoupling of pure genetic inputs from pure mechanical inputs in the
      regulation of gene expression and myosin-II patterning. Specifically, we describe
      the innovative magnetic tweezers tools we have set up to measure and apply
      physiological strains and forces in vivo, from the inside of the tissue, to
      modulate and mimic morphogenetic movements in living embryos. We discuss
      mechanical induction incidence in tumor development and perspective in evolution.

PMID- 20816240
TI  - Informatics-based analysis of mechanosignaling in the laminopathies.
AB  - The A- and B-type lamins are the primary building blocks of the lamina-a
      proteinaceous meshwork underlying the nuclear envelope (NE). In the last decade,
      some 25 diseases have been linked to mutations in genes encoding proteins of the
      NE and lamina, with about half being caused by mutations in the Lamin A gene.
      Cells, either from patients or from mice carrying lamin mutations, frequently
      exhibit deformed nuclei accompanied by compromised mechanical properties in both
      the nucleus and the cytoplasm, implying that defects in the mechanical integrity
      of the nuclei and in mechanosignaling contribute to the pathology of these
      diseases. We describe a procedure to study total gene expression of mutant cells
      subjected to uniaxial mechanical strain by culturing them on a deformable
      surface. Using our procedure, enough high-quality RNA can be collected from these
      samples for microarray and informatics analysis. Such analysis may provide
      valuable information regarding the changes in gene expression and signaling
      pathways that may underlie the pathologies of the various diseases, which in turn
      may arise as a consequence of defective responses to mechanical strain.

PMID- 20816241
TI  - Autosomal dominant leukodystrophy caused by lamin B1 duplications a clinical and
      molecular case study of altered nuclear function and disease.
AB  - Autosomal dominant leukodystrophy (ADLD) is an adult-onset demyelinating disorder
      that has recently shown to be caused by duplications of the nuclear lamina gene,
      lamin B1. This chapter attempts to collate and summarize the current knowledge
      about the disease and the clinical, pathological, and radiological presentations
      of the different ADLD families described till date. It also provides an overview
      of the molecular genetics underlying the disease and the mechanisms that may
      cause the duplication mutation event. ADLD is the first disease that has ever
      been linked to lamin B1 mutations and it expands the pathological role of the
      nuclear lamia to include disorders of the brain. The chapter also speculates on
      the different mechanisms that may link an important and ubiquitous structure like
      the nuclear lamina with the complex and cell-specific functions of myelin
      formation and maintenance. Understanding these mechanisms may not only prove
      helpful in understanding ADLD pathology but can also help in identifying new
      pathways that may be involved in myelin biology that can have implications for
      common demyelinating diseases like multiple sclerosis.

PMID- 20816244
TI  - Oral administration of beta-1,3/1,6-glucan Macrogard fails to enhance the mucosal
      immune response following oral F4 fimbrial immunisation in gnotobiotic pigs.
AB  - In this study gnotobiotic animals were used to see if the F4 fimbrial antigen of
      F4ac+ Escherichia coli is as immunogenic as in conventional pigs. In addition,
      the adjuvant effect of beta-1,3/1,6-glucans was analysed for the first time in
      germ-free domestic animals. Oral F4 immunisation of F4 receptor positive (F4R(+))
      piglets was able to induce a systemic and mucosal immune response as conventional
      pigs, although less pronounced. Nevertheless, an IgA response was observed in
      Peyer's patches and mesenteric lymph nodes. Moreover, a dose dependent effect was
      observed. Oral administration of beta-glucans for 5 weeks was not able to enhance
      this F4-specific immune response. The only effect of the beta-glucan treatment we
      observed was a significantly higher IL-1 alpha mRNA expression in the spleen. No
      significant changes in total serum antibody concentrations and in the volume of
      the ileal Peyer's patches were seen.

PMID- 20816245
TI  - Steller sea lion (Eumetopias jubatus) pups undergo a decrease in circulating
      white blood cells and the ability of T cells to proliferate during early
      postnatal development.
AB  - Postnatal changes in circulating immune components and peripheral blood
      mononuclear cell (PBMC) proliferation were assessed in Steller sea lion pups
      (SSL; Eumetopias jubatus). Blood samples were collected for complete blood cell
      counts including total and differential white blood cell (WBC) counts from 46
      pups ranging in age from 5 to 38 days old. Total WBC and neutrophil counts
      decreased in association with increased age of the pups. The ability of PBMC to
      proliferate was assessed by in vitro exposure to concanavalin A (ConA) or
      lipopolysaccharide (LPS) in 21 pups ranging in age from 7 to 32 days old. All SSL
      pups responded to in vitro stimulation with ConA and LPS 055:B5 indicating
      peripheral T and B cells are capable of responding to an antigenic challenge.
      ConA-induced T cell proliferation decreased with age while there was no change in
      spontaneous proliferation of PBMC or B cells exposed to LPS. The decreases in
      total WBC, neutrophil counts and T cell proliferation indicates that SSL undergo
      a period of postnatal development in cell-mediated immune function which is
      comparatively longer than phocid pups and consistent with other otariids.

PMID- 20816246
TI  - Glaucoma screening in the real world.

PMID- 20816247
TI  - Diagnostic accuracy of the Heidelberg Retina Tomograph for glaucoma a population
      based assessment.
AB  - OBJECTIVE: To evaluate the Heidelberg Retina Tomograph II (HRTII; Heidelberg
      Engineering, Heidelberg, Germany) as a screening tool for open-angle glaucoma
      (OAG) in an older population. DESIGN: Population-based, cross-sectional study.
      PARTICIPANTS: Participants from the 10-year follow-up Blue Mountains Eye Study (n
      = 1952; 75.6% of survivors). METHODS: Participants underwent optic nerve head
      imaging performed using the HRTII; OAG was diagnosed independently from optic
      disc photographs and Humphrey 24-2 visual fields. MAIN OUTCOME MEASURES: The
      Moorfields Regression Analysis (MRA) was applied to scans using the default
      results of "normal," borderline," and "outside normal limits." Outcome
      classification was at the person level and used data from both eyes. RESULTS:
      Mean age was 73.7 years. The HRT scans could be acquired in 1644 participants,
      95.9% of those fully examined; 87.4% of scans having a topography standard
      deviation (TSD) < or =40 microm. Larger TSD was associated with older age and
      OAG. The MRA sensitivity was 64.1%, specificity 85.7%, positive predictive value
      21%, and negative predictive value 97.6% for detecting OAG. Including borderline
      results improved sensitivity (87.0%) but specificity dropped to 70.6%.
      Significant predictors of abnormal MRA included OAG (odds ratio [OR], 7.70; 95%
      confidence interval [CI] 4.79-12.35), age (OR, 1.05; 95% CI, 1.03-1.07), TSD (OR,
      1.01; 95% CI, 1.003-1.020) and disc size (OR, 3.2; 95% CI, 2.31-4.49). Diagnostic
      accuracy was improved by restricting TSD <40 microm. Further TSD restriction
      improved specificity at the expense of sensitivity. As disc size increased,
      specificity fell whereas sensitivity, OAG prevalence, and the proportion testing
      positive rose. Glaucoma prevalence, positive predictive value, and the proportion
      testing positive increased, but specificity fell with increasing age. Sensitivity
      also fell between youngest and oldest groups. Diagnostic performance improved for
      visual field mean deviation < -4.0 dB. Single eye analyses overestimated
      specificity and underestimated sensitivity compared with using data from both
      eyes. CONCLUSIONS: Diagnostic test evaluation studies of HRTII using single eye
      analyses or restrictive selection overestimate test accuracy compared with this
      population-based study. Although the specificity of the MRA was inadequate for
      use as a glaucoma screening test, the HRTII performed relatively well in an
      unselected older population with acceptable quality scans in most eyes.

PMID- 20816248
TI  - Small-gauge pars plana vitrectomy: a report by the American Academy of
      Ophthalmology.
AB  - OBJECTIVE: To review available peer-reviewed publications to evaluate the safety
      profile and visual outcomes associated with small-gauge pars plana vitrectomy.
      METHODS: Literature searches of the PubMed and the Cochrane Library databases
      were last conducted on August 5, 2009, with no date restrictions. The searches
      were limited to articles published in English. These searches retrieved 328
      articles, of which 76 were deemed topically relevant and rated according to
      strength of evidence. RESULTS: On the basis of level II and level III evidence,
      the overall safety profile of small-gauge pars plana vitrectomy is similar to
      that established for conventional 20-gauge pars plana vitrectomy and provides
      comparable visual acuity results. An increased incidence of infectious
      endophthalmitis after 25-gauge vitrectomy was reported in 2 comparative studies,
      but this was not found in multiple, larger, more recent studies, perhaps due to
      modifications in case selection and surgical technique over time. Compared with
      20-gauge vitrectomy, small-gauge vitrectomy is associated with significantly
      lower levels of patient discomfort and ocular inflammation, and the time required
      for improvement in visual acuity is shorter. CONCLUSIONS: The technological
      advances of small-gauge vitrectomy seem to afford visual benefit comparable with
      that seen with traditional 20-gauge surgery, with more rapid healing, less
      discomfort, and an acceptably low incidence of adverse events comparable with
      those observed with conventional 20-gauge vitrectomy. As surgical techniques
      evolve and clinical experience grows, continued close surveillance is necessary
      for an accurate assessment of complications.

PMID- 20816249
TI  - Combination therapy for retinal vein occlusion.

PMID- 20816250
TI  - Microplasmin for vitreomacular traction.

PMID- 20816253
TI  - Ranibizumab and stroke.

PMID- 20816254
TI  - Nerve fiber layer thickness.

PMID- 20816255
TI  - Interferon for melanoma.

PMID- 20816256
TI  - IOL tilt and decentration.

PMID- 20816257
TI  - Assessing ophthalmoscopy skills.

PMID- 20816259
TI  - Thyroid-associated orbitopathy.

PMID- 20816260
TI  - Sample stability for the measurement of hemoglobin A1c.

PMID- 20816262
TI  - Neurochemistry International. Editorial.

PMID- 20816261
TI  - Improvement of psoriatic arthritis by pioglitazone treatment in a type 2 diabetic
      patient.

PMID- 20816263
TI  - Advances in neurologic therapy. Preface.

PMID- 20816264
TI  - Neurostimulation in headache disorders.
AB  - Although headache is a common ailment, its more severe manifestations such as
      intractable migraine, and trigeminal autonomic cephalagias including cluster
      headaches have a debilitating effect on patients resulting in chronic pain and
      severe functional impairment. Neurostimulation has been explored as a possible
      treatment option in selective drug-resistant primary headache disorders, in
      conducting clinical trials involving neurostimulation of deep brain structures,
      occipital nerves, and vagal nerves as treatment methods for refractory primary
      headache disorders, the selection of patients should be strictly based on pre
      defined clinical criteria. The trials should be well designed, taking into
      account the potential risks and complications associated with such therapies.

PMID- 20816265
TI  - The selection of antiepileptic drugs for the treatment of epilepsy in children
      and adults.
AB  - In the past 2 decades, 12 new antiepileptic drugs (AED) have been approved by the
      Food and Drug Administration for the treatment of epilepsy, making the selection
      process more complex. When choosing an AED several factors are considered
      including its relative efficacy, tolerability, serious toxicity, ease of use
      (determined by the pharmacokinetic profile and the drug-drug interaction
      potential), the presence of comorbid conditions, and cost. Age and gender are
      also important considerations. The tradition of recognizing a first-choice drug
      for a certain seizure type or epilepsy syndrome is no longer a practical concept.
      With so many AED available, depending on several factors, different patients with
      a similar type of epilepsy may be prescribed entirely different AED. The newer
      AED have shown no better efficacy than the classic drugs, but they are easier to
      use, with much better pharmacokinetic profiles and fewer drug interactions. The
      list of broad-spectrum drugs has greatly expanded, a major benefit for patients
      with generalized epilepsies. The long list of available AED has also benefited
      patients with epilepsy and comorbidities, often allowing for the use of drugs
      with positive or at least no negative effects on those conditions. Some practical
      recommendations on the selection of AED are provided in this article.

PMID- 20816266
TI  - Management of status epilepticus in adults.
AB  - Status epilepticus (SE) may cause death or severe sequelae unless seizures are
      terminated promptly. Various types of SE exist, and treatment should be adjusted
      to the specific type. Yet some basic guiding principles are broadly applicable:
      (1) early treatment is most effective, (2) benzodiazepines are the best first
      line agents, (3) electroencephalography should be used to confirm the termination
      of seizures in patients who are not alert and to monitor therapy in refractory
      cases, and (4) close attention to the appearance of systemic complications (from
      the SE per se or from the medications used to treat it) is essential. This
      article expands on these principles and summarizes current knowledge on the
      definition, classification, diagnosis, and treatment of SE.

PMID- 20816267
TI  - Management of arterial blood pressure in acute ischemic and hemorrhagic stroke.
AB  - It is essential to control arterial blood pressure (BP) in both hemorrhagic and
      ischemic stroke patients to decrease morbidity following an acute event and
      decrease the long-term risk of stroke recurrence. Pathophysiology of BP control
      is dependent on understanding key relationships of cerebral blood flow and
      cerebral perfusion pressure. In the long term, hypertensive control decreases the
      rate of incident and recurrent hemorrhagic and ischemic stroke. In the acute
      setting, neither when to start antihypertensive medication nor the optimal BP
      target goals for short- and long-term control are well defined. There are several
      different drug classes available for BP control, with considerable debate as to
      which drugs are preferred for stroke patients. Medication selection and target BP
      depend on individual patient characteristics, including type of stroke, medical
      comorbidities, and timing of interventions in the context of the acute or
      postacute phases of stroke.

PMID- 20816268
TI  - Modern management of brainstem cavernous malformations.
AB  - Over the last 2 decades, there have been dramatic advancements in our
      understanding of and the ability to treat brainstem cavernous malformations
      (BCMs). Once thought untreatable, BCMs are now being more aggressively and safely
      treated microsurgically as a result of advances in monitoring and imaging
      technologies, as well as refinement of surgical techniques. BCMs deemed
      inoperable are being treated with radiosurgery, and experience with dosing and
      targeting has improved the safety of this treatment modality as well. Much work
      remains to be done, and prospective randomized trials would undoubtedly further
      existing knowledge.

PMID- 20816269
TI  - Endovascular management of intracranial dural arteriovenous fistulas.
AB  - Classification, pathophysiology, and endovascular treatment of intracranial dural
      arteriovenous fistulas are discussed. Risk for neurologic deterioration is based
      on the presence and extent of cortical venous reflux. Previous endovascular
      techniques relied heavily on transvenous coil embolization. Recent advances in
      endovascular materials have facilitated the treatment and cure of many of these
      lesions via transarterial approaches. Penetration of liquid embolic agent into
      the nidus and foot of the draining vein is crucial for long-term angiographic
      cure.

PMID- 20816270
TI  - Management of motor complications in Parkinson disease: current and emerging
      therapies.
AB  - Motor fluctuations and dyskinesias are common motor complications that manifest
      within the first few years from the initiation of therapy in patients with
      Parkinson disease. These complications negatively affect the quality of life and
      represent an important source of disability. A growing number of therapeutic
      options including treatments aimed at prolonging the efficacy of levodopa (eg,
      selective monoamine oxidase-B inhibitors and catechol-O-methyltransferase
      inhibitors), administration of longer-acting dopamine agonists (eg, rotigotine,
      sustained-release ropinirole), and continuous administration of intraduodenal
      levodopa exist or will soon become available. Patients who maintain a good
      response to levodopa but continue to experience disabling motor complications
      despite the best medical management may benefit from a regimen of subcutaneous
      apomorphine, ideally delivered by a subcutaneous pump, or deep-brain stimulation
      of the subthalamic nucleus or internal portion of the pallidum. Emerging
      therapies for motor complications are expected to further enhance continuous
      (physiologic) delivery of dopaminergic drugs and extend the reach of therapies
      beyond the dopaminergic system to influence not only the motor but also the vast
      range of nonmotor complications of this multisystemic disease.

PMID- 20816271
TI  - Therapeutic challenges in dystonia.
AB  - Because dystonia can vary in clinical presentation and etiology, proper diagnosis
      and classification of these disorders are important in making therapeutic
      decisions. In primary dystonia, treatment is generally geared toward alleviating
      symptoms rather than curing the underlying condition, therefore severity of
      contractions, pain, and functional and social impact are also factors to consider
      in determining if and how to initiate therapy. On the other hand, if a secondary
      cause is identified, then it is often appropriate to direct treatment toward the
      underlying disorder. Treatment options include physical and occupational therapy,
      oral medications, botulinum toxin, and surgery. This article briefly reviews the
      clinical features, pathophysiology, and classification of dystonia before
      reviewing current therapeutic options.

PMID- 20816273
TI  - Management of critical illness polyneuropathy and myopathy.
AB  - A syndrome of generalized weakness, areflexia, and difficulty with weaning from a
      ventilator is a common clinical presentation in the critically ill patient,
      especially in the setting of sepsis, multiorgan failure, and hyperglycemia. At
      first believed to be a manifestation of nerve (critical illness neuropathy, CIN)
      or muscle (critical illness myopathy, CIM) dysfunction, our current
      conceptualization is as a spectrum (critical illness neuromuscular abnormalities,
      CINMA) that varies in extent and site(s) of involvement, but often a similar
      clinical presentation. Signs and symptoms of CINMA must be identified early to
      foster recovery and limit morbidity and mortality. The medical history is crucial
      in excluding preexisting neuromuscular conditions and electrodiagnostic testing
      helps to establish the diagnosis and prognostication. A stepwise approach to the
      management of a patient with CINMA is outlined, but avoiding potential
      medications, and ensuring supportive care are the primary interventions to
      consider. Recently intensive insulin therapy for hyperglycemia has been shown to
      lower the risk of CINMA and decrease the time of ventilatory support, but with a
      greater risk of hypoglycemia. Future therapeutic interventions will require a
      better understanding of disease pathogenesis, but may target proinflammatory
      cytokine and free-radical pathways, muscle gene expression, ion channel function,
      or proteolytic muscle protein mechanisms. Rehabilitation is an equally essential
      component in a patient's management. Although prognosis depends on the extent of
      the underlying muscle and nerve damage, mild persistent deficits are common and
      severe disability may be persistent.

PMID- 20816272
TI  - Management of voltage-gated potassium channel antibody disorders.
AB  - Syndromes from antibodies to voltage-gated potassium channels include
      neuromyotonia (NMT), limbic encephalitis (LE) and Morvan syndrome (MVS). There
      are distinct clinical features for NMT (cramps, stiffness, fasciculations,
      myokymia, hyperhidrosis; afterdischarges and continuous motor activity on
      electromyogram), LE (encephalopathy with seizures, deficient recent memory;
      hyponatremia, temporal lobe magnetic resonance imaging and
      electroencephalographic abnormalities) and MVS (NMT plus hyperhidrosis,
      dysautonomia, encephalopathy, severe insomnia, and sleep disorders). There may be
      associated myasthenia gravis or thymoma, and rarely lung cancer (small cell or
      adenocarcinoma), mandating that chest imaging be part of the evaluation. Most
      cases respond favorably to immunosuppression with plasma exchange, intravenous
      immunoglobulin or pulse intravenous methylprednisolone, usually followed by oral
      steroids.

PMID- 20816274
TI  - What's new in the diagnosis and treatment of peripheral nerve entrapment
      neuropathies.
AB  - Entrapment neuropathies can be common conditions with the potential to cause
      significant disability. Correct diagnosis is essential for proper management.
      This article is a review of recent developments related to diagnosis and
      treatment of various common and uncommon nerve entrapment disorders. When
      combined with classical peripheral nerve examination techniques, innovations in
      imaging modalities have led to more reliable diagnoses. Moreover, innovations in
      conservative and surgical techniques have been controversial as to their effects
      on patient outcome, but randomized controlled trials have provided important
      information regarding common operative techniques. Treatment strategies for
      painful peripheral neuropathies are also reviewed.

PMID- 20816275
TI  - Treatments for neuro-ophthalmologic conditions.
AB  - Neuro-ophthalmology covers disorders that fall between the cracks of Neurology
      and Ophthalmology. Neurologists see patients with neuro-ophthalmic disorders.
      Recognition of the diagnosis is difficult enough, but treatment can be
      challenging. This article reviews several common neuro-ophthalmic disorders,
      outlining their features and treatments, from retinal vascular disorders to eye
      movements and blepharospasm.

PMID- 20816276
TI  - Management of diffuse low-grade cerebral gliomas.
AB  - World Health Organization grade II gliomas (GIIG) are diffuse, slow-growing,
      primary neuroectodermal tumors that occur in the central nervous system. They are
      generally seen in young individuals and are slightly more common in Whites and
      males. Most patients present with seizures but neurologic deficits are rare.
      Magnetic resonance imaging best detects GIIG and they are most frequently located
      in the frontal and temporal lobes. An accurate pathologic diagnosis is essential
      because the natural history of a GIIG may be unpredictable. In recent years, the
      emphasis has been on surgically removing as much tumor as safely possible to
      obtain an accurate diagnosis, improve symptoms, reduce tumor burden, and
      determine the need for adjuvant therapies. Radiation and chemotherapy are
      integral to the management of GIIG but their efficacy varies by tumor histology
      and is balanced against complications associated with them. Genetic,
      histopathologic, clinical, and radiographic changes are noted as GIIG progress to
      malignant gliomas. The risk of malignant transformation and subsequent survival
      may be predicted by pretreatment and treatment-related factors.

PMID- 20816277
TI  - Management of acute, recurrent, and chronic meningitides in adults.
AB  - Meningitis (inflammation of the pia, arachnoid, and sometimes dura) has diverse
      causes and presentations. Although viruses are the most common cause of acute
      meningitis, bacterial meningitides are more severe and important to exclude
      because morbidity and mortality are high. Chronic meningitis has a broader range
      of causes, including atypical bacteria, fungi, and noninfectious causes.
      Presentation is more insidious but, if untreated, significant damage or death may
      ensue. Recurrent meningitis has many of the same causes as chronic meningitis,
      but manifestations occur in discrete episodes. Distinguishing between acute,
      chronic, and recurrent meningitis is essential for proper diagnostic testing and
      treatment approaches.

PMID- 20816278
TI  - Treatment options for parasomnias.
AB  - Parasomnias are undesirable physical or experiential events that occur in and
      around sleep. Treatments include reassurance in some cases, various forms of
      cognitive-behavioral therapy (CBT), and pharmacologic agents. Cognitive
      restructuring, imagery rehearsal, relaxation, hypnosis, desensitization, and
      anticipatory awakenings are some of the common CBT and nonpharmacologic
      interventions. Medications that are used belong to a wide variety of
      pharmacologic classes, such as alpha-blockers (prazosin), tricyclic
      antidepressants (imipramine and clomipramine), selective serotonin reuptake
      inhibitors, benzodiazepines (diazepam and clonazepam), anticonvulsants
      (topiramate and gabapentin), desmopressin acetate, and anticholinergic agents
      (oxybutynin and tolterodine). Data on efficacy are only available from randomized
      trials on CBT and prazosin for nightmares and on pharmacologic and alarm therapy
      for enuresis. No large-scale randomized trials are available to assess the
      efficacy of the other treatments, and most data come from anecdotal case reports,
      case series, or small open-label trials.

PMID- 20816281
TI  - Financial conflicts of interest policies: From confusion to clarity.

PMID- 20816282
TI  - In the land of no evidence, is the salesman king?

PMID- 20816284
TI  - Expectations, acceptance, and preferences regarding microimplant treatment in
      orthodontic patients: A randomized controlled trial.
AB  - INTRODUCTION: In this study, we evaluated the pain and discomfort experienced by
      orthodontic patients by comparing how they rated pain associated with had
      microimplant placement, tooth extraction, and gingival tissue removal in
      preparation for implant placement. METHODS: Fifty-six microimplants were placed
      in 28 consecutive orthodontic patients for anchorage reinforcement in the maxilla
      for en-masse retraction. For all patients, extractions of maxillary, or maxillary
      and mandibular, premolars had been planned. The recruited patients were
      randomized into 2 groups according to the timing of the extractions. In group A,
      at least 1 extraction was performed during the evaluation period; the extractions
      in group B were after the evaluations. Furthermore, all patients had 2 different
      surgical procedures for placement. On 1 side, the gingival tissue was removed
      before placement. On the contralateral side, the implant was placed
      transgingivally. Each patient's perception of pain and discomfort was evaluated
      by a questionnaire before, immediately after, and 1 week after the intervention.
      RESULTS: The discomfort experienced during the extractions was described as very
      painful by 50% of the patients. It was significantly greater than during tissue
      removal and microimplant placement (P <0.05). Microimplant placement produced no
      pain in 30% of the patients and was described as the least painful procedure (P
      <0.05). Transgingival microimplant placement was significantly preferred by all
      patients (P <0.05). CONCLUSIONS: Microimplant surgery seems to be a well-accepted
      treatment option in orthodontic patients, with significantly lower pain levels
      than for tooth extractions. Furthermore, transgingival placement is clearly
      favored by patients who do not need tissue removed before placement.

PMID- 20816286
TI  - Anatomic variability in alveolar sites for skeletal anchorage.
AB  - INTRODUCTION: Because alveolar bone is used for skeletal anchorage, the
      variability and reliability of its dimensions are important. METHODS:
      Interradicular distances, cortical thicknesses, and buccolingual spaces were
      measured on computed tomography images of 22 adults (13 maxillary and 9
      mandibular). Intra-arch analyses were done with paired t tests; the interarch
      comparisons were studied with independent t tests. The intraclass correlation
      coefficient was calculated between corresponding units. RESULTS: Interradicular
      distances were greater for the molars than for the incisors, and apical distances
      were greater than cervical. The mandibular lingual cortical thickness was the
      greatest, and the maxillary buccal cortical thickness was less than the
      mandibular in the molar apical zones. The widest and narrowest buccolingual
      spaces were found at the maxillary molars and the mandibular incisors,
      respectively. The cross values of cortical bone thickness were wider than the
      axial means and they had low agreement, so they had interradicular distances on
      the right and left sides. CONCLUSIONS: Although interradicular distances must be
      carefully assessed, the molars were favorable sites for skeletal anchorage.
      Placing anchorage in anterior sites requires even more careful planning,
      including the use of computed tomography records.

PMID- 20816288
TI  - Long-term stability of surgical-orthodontic open-bite correction.
AB  - INTRODUCTION: The objective of this study was to evaluate the long-term stability
      of open-bite surgical-orthodontic correction. METHODS: Thirty-nine patients at an
      initial mean age of 20.83 years were evaluated cephalometrically at pretreatment
      (T1), immediately after treatment (T2), and at the last recall (T3), with a mean
      follow-up time of 8.22 years. The surgical protocol included single-jaw or double
      jaw surgery. Because the patients had different anteroposterior malocclusions,
      the sample was divided into a Class I and Class II (I-II) subgroup (3 Class I, 20
      Class II malocclusion patients) and a Class III subgroup (16 patients). The
      dentoskeletal characteristics of the total sample and the subgroups were compared
      at T1, T2, and T3 with dependent analysis of variance (ANOVA). RESULTS: Overbite
      relapse in the posttreatment period was statistically significant in the whole
      sample and the Class I-II subgroup. Fourteen patients of the whole sample (35.9%)
      had clinically significant open-bite relapse (negative overbite). CONCLUSIONS:
      There was a statistically significant open-bite relapse in the overall sample and
      in the Class I-II subgroup. The clinically significant values of long-term open
      bite correction stability were 64.11%, 47.82%, and 87.50% in the overall sample,
      the Class I-II subgroup, and the Class III subgroup, respectively.

PMID- 20816290
TI  - Effect of arch form on the fabrication of working archwires.
AB  - INTRODUCTION: Previous studies have shown that most practitioners plan to
      maintain intercanine and intermolar widths during orthodontic treatment with
      fixed appliances. The aim of this study was to determine whether this was put
      into practice by clinicians during the latter stages of orthodontic treatment
      with fixed appliances. METHODS: This 2-part investigation was a laboratory-based
      measurement study at Bristol Dental Hospital, United Kingdom, from 2005 to 2007.
      Using standardized maxillary and mandibular study models with identical
      intermolar and intercanine widths but with differing degrees of tooth
      misalignment, 30 clinicians were asked to fabricate final working archwires
      according to their normal clinical practice. Then the intercanine and intermolar
      widths of the archwires were measured. In the second part of the study, the same
      intra-arch dimensions were measured directly from 50 pretreatment and
      posttreatment patient study models obtained from a subsample of 10 of the
      clinicians. RESULTS: The intercanine and intermolar widths measured on the
      adapted archwires from the standardized study models showed wide variations in
      the results, even though the intercanine and intermolar widths of the models were
      identical. Data from 50 treated patients also showed that, in most, there were
      wide variations in intercanine and intermolar widths between the patients'
      pretreatment and posttreatment study models. CONCLUSIONS: Although most
      clinicians aim to maintain the pretreatment arch form, this study shows that this
      is often not transferred to clinical practice.

PMID- 20816292
TI  - A new concept of anatomic lingual arch form.
AB  - INTRODUCTION: The aim of this study was to describe a natural and anatomic
      lingual arch form obtained from subjects with normal occlusion that could be
      used, with other criteria, in the construction of personalized setups for the
      lingual straight-wire technique. METHODS: The study sample comprised 58 pairs of
      dental casts of the arches of 58 southern Europeans (37 women, 21 men) with ideal
      natural occlusions. After the reference points of the dental arches were
      identified and marked, the dental casts were scanned. The exact position of the
      models on the scanner was established by using an acetate sheet with a Cartesian
      reference system. For each image, 14 reference points (x, y) were measured and
      recorded. The measurements were processed with software to select the polynomial
      function that best described the shape of the dental arches. The ninth-degree
      polynomial function was selected to represent the lingual arch form of both
      arches. Distribution analysis of the x and y values of each tooth in each arch
      resulted in the creation of 3 groups (small, medium, and large) to verify the
      most appropriate measures of the central tendencies of our data. RESULTS:
      Statistical analysis showed no significant sex difference in the medians of the 6
      parameters used to measure depth and width in both arches. A representation of
      the variability of the lingual curve of our sample was created to document at
      least 3 sizes of the representative curve of the central tendency for our data.
      No statistically significant differences in shape were found between men and
      women, considering the medians as a measure of the central tendencies.
      CONCLUSIONS: Three lingual curves (small, medium, and large) for the maxillary
      and mandibular arches, representing the mean values of our sample, were developed
      and can be used as guides for the setup in the lingual straight-wire technique.

PMID- 20816294
TI  - Preliminary cone-beam computed tomography study evaluating dental and skeletal
      changes after treatment with a mandibular Schwarz appliance.
AB  - INTRODUCTION: The purpose of this study was to evaluate the efficacy of the
      Schwarz appliance with a new method of superimposing detailed cone-beam computed
      tomography (CBCT) images. METHODS: The subjects were 28 patients with Angle Class
      I molar relationships and crowding; they were randomly divided into 2 groups: 14
      expanded and 14 nonexpanded patients. Three-dimensional Rugle CBCT software
      (Medic Engineering, Kyoto, Japan) was used to measure 10 reference points before
      treatment (T0) and during the retention period of approximately 9 months after 6
      to 12 months of expansion (T1). Cephalometric and cast measurements were used to
      evaluate the treatments in both groups. Also, the mandibular widths of both
      groups were measured along an axial plane at 2 levels below the cementoenamel
      junction from a CBCT scan. Differences between the 2 groups at T0 and T1 were
      analyzed by using the Mann-Whitney U test. RESULTS: The dental arch (including
      tooth root apices) had expanded; however, alveolar bone expansion was only up to
      2 mm below the cementoenamel junction. There was a statistically significant (P
      <0.05) difference between the groups in terms of crown, cementoenamel junction,
      root, and upper alveolar process. However, no significant (P >0.05) differences
      were observed in the interwidths of the mandibular body, zygomatic bones,
      condylar heads, or mandibular antegonial notches. In the mandibular cast
      measurements, arch crowding and arch perimeter showed statistically significant
      changes in the expanded group. The buccal mandibular width and lingual mandibular
      width values had significant changes as measured from a point 2 mm below the
      cementoenamel junction. CONCLUSIONS: The findings suggest that the Schwarz
      appliance primarily affected the dentoalveolar complex, but it had little effect
      on either the mandibular body or any associated structures. In addition, the
      molar center of rotation was observed to be below the root apex.

PMID- 20816295
TI  - Cone-beam computed tomography evaluation of mini-implants after placement: Is
      root proximity a major risk factor for failure?
AB  - INTRODUCTION: The purposes of this study were to determine factors favoring
      successful mini-implant placement and to evaluate root proximity as a possible
      risk factor for failure of osseointegration-based mini-implants during
      orthodontic treatment. METHODS: Three-dimensional cone-beam computed tomography
      images were used to examine 50 sandblasted, large-grit, and acid-etched surface
      treated mini-implants (C-implant, Seoul, Korea) placed in 25 patients. The images
      were analyzed for 3-dimensional position of the mini-implant (placement angle and
      depth) and any contact with root surfaces or maxillary sinuses. RESULTS: There
      were no remarkable differences in horizontal placement angles in the axial plane
      and placement depths of the mini-implants, but the vertical placement angle was
      significantly higher on the left side (24.5 degrees +/- 11.0 degrees ) compared
      with the right side (11.8 degrees +/- 11.6 degrees ). The horizontal mini-implant
      placement angle had a greater inclination tendency toward the maxillary first
      molar, and 11 mini-implants with root proximity showed mesiobuccal contact with
      the maxillary first molar root. Only 1 failure in 15 mini-implants with root
      proximity and 1 failure in 35 without root proximity were observed on the images.
      CONCLUSIONS: Root proximity alone was not considered a major risk factor for
      osseointegration-based mini-implant failure.

PMID- 20816296
TI  - Long-term development of malocclusion traits in orthodontically treated and
      untreated subjects.
AB  - INTRODUCTION: The purposes of this study were to analyze long-term changes in
      malocclusion traits and to compare the development in orthodontically treated and
      untreated subjects. METHODS: The sample comprised 308 adolescents in the
      intermediate, late mixed, or early permanent dentition who were examined
      clinically at the ages of 8 to 17 years and again 25 years later. The treated
      subgroup of 58 subjects had received orthodontic treatment with fixed or
      removable appliances or both. All subjects had a full complement of teeth, except
      a subgroup of 19 who had premolar extractions as a part of their orthodontic
      treatment plan. RESULTS: The prevalence of maxillary overjet was significantly
      reduced in the untreated group and the treated subgroups. The prevalence of
      distal molar occlusion was significantly reduced in the subgroup treated without
      extractions. Comparison of treated and untreated groups in terms of changes over
      time showed that development was significantly more favorable in all treatment
      categories regarding maxillary overjet, and in the nonextraction category
      regarding distal molar occlusion. Subjects treated without extractions had less
      favorable development than did untreated subjects regarding molar crossbite.
      CONCLUSIONS: The long-term benefit of orthodontic treatment, with or without
      extractions, was confirmed regarding maxillary overjet, and the lasting effect of
      nonextraction treatment was confirmed regarding the distal molar relationship.
      The pattern of changes in treated and untreated subjects indicated that long-term
      development and individual variation can to some extent conceal the effects of a
      brief orthodontic intervention.

PMID- 20816297
TI  - Modified fluoride toothpaste technique reduces caries in orthodontic patients: A
      longitudinal, randomized clinical trial.
AB  - INTRODUCTION: The hypothesis of this study was that toothpaste slurry rinsing,
      combined with other simple postbrushing steps (the modified fluoride toothpaste
      technique [MFTT]), would reduce the number of decayed and filled tooth surfaces.
      METHODS: The study population consisted of 100 orthodontic patients randomly
      divided into 2 groups, 51 in the test group (mean age, 16.2 +/- 4 years) and 49
      in the control group (mean age, 16.9 +/- 4 years). Each patient was examined
      before starting orthodontic treatment (baseline) and shortly after debonding
      (follow-up) in a 2-year study period. At each of these 2 visits, the patients
      were examined in the following order: interviewed by using a standardized
      questionnaire, plaque index registration, intraoral clinical examination, and
      radiographic examination (bitewings). The test group patients were instructed to
      use the MFTT. The control group patients were given the same fluoridated
      toothpaste as the test group and the routine clinical oral hygiene instructions.
      RESULTS: Compared with the control group, the test group had significantly better
      plaque index scores at the end of the study. At follow-up, the clinical (P
      <0.001), radiographic (P <0.001), and clinical plus radiographic (P <0.001)
      incidences of decayed and filled surfaces were significantly reduced: 87%, 78%,
      and 83%, respectively, in the test group compared with the control group.
      CONCLUSIONS: Compared with routine oral hygiene instructions with fluoride
      toothpaste, the use of the MFTT significantly reduced the incidence of new
      carious lesions in orthodontic patients. We believe that this simple regimen
      should be considered in orthodontic clinics.

PMID- 20816298
TI  - Volumetric, planar, and linear analyses of pharyngeal airway change on computed
      tomography and cephalometry after mandibular setback surgery.
AB  - INTRODUCTION: The purpose of this study was to use lateral cephalometry and
      computed tomography (CT) to examine the volumetric, planar, and linear changes in
      the pharyngeal airway after mandibular setback surgery. METHODS: The pharyngeal
      airways of 12 subjects who underwent mandibular setback surgery at Seoul National
      University Dental Hospital were assessed linearly and volumetrically on lateral
      cephalometric radiographs and CT before surgery and 6 months after surgery. The
      pharynx, nasopharynx, and oropharynx were evaluated by volumetric analysis.
      Pharyngeal depth, airway space, pharyngeal soft-tissue thickness, and hyoid bone
      position were measured by linear analysis. The axial section area of the airway
      was measured by area analysis. RESULTS: From the linear analysis, a significant
      decrease in pharyngeal depth and a significant posterior movement of the hyoid
      bone (P <0.05) were noted. Volumetric analysis by CT showed that the oropharynx
      decreased after mandibular setback surgery. However, the volume and the axial
      section area of the airway in the CT images did not change significantly after
      mandibular setback surgery (P >0.05). CONCLUSIONS: Although the structures around
      the mandible inevitably moved backward after mandibular setback surgery on linear
      analysis, physiologic deformation could occur to preserve the airway capacity
      after sagittal compression.

PMID- 20816299
TI  - Treatment and posttreatment effects of a facial mask combined with a bite-block
      appliance in Class III malocclusion.
AB  - INTRODUCTION: In this cephalometric investigation, we analyzed the treatment and
      posttreatment effects of an orthopedic protocol for Class III malocclusion
      consisting of a facial mask combined with a removable bite-block appliance.
      METHODS: The treated sample consisted of 22 Class III patients treated with the
      facial mask and bite-block protocol before the pubertal growth spurt (mean age,
      8.9 +/- 1.5 years). Treated subjects were evaluated after facial mask and bite
      block therapy and at a posttreatment observation in absence of retention. The
      treated group was compared with a matched control group of 12 untreated Class III
      subjects. All treated and control subjects were postpubertal at the final
      observation. Significant differences between the treated and control groups were
      assessed with the Mann-Whitney U test (P <0.05). RESULTS: Both angular and linear
      sagittal measurements of the maxilla showed significant improvements during
      active treatment. Significant improvements of SNA angle, ANB angle, overjet, and
      molar relationship remained stable during the posttreatment period. No
      significant effect was found in the mandibular skeletal measures. No significant
      protraction of the maxillary incisors or retraction of the mandibular incisors
      was observed. CONCLUSIONS: A bite-block appliance in the mandibular arch with a
      facial mask enabled effective control of mandibular rotation with progressive
      closure of the gonial angle. This added to the favorable maxillary outcomes of
      the treatment protocol.

PMID- 20816300
TI  - Treatment and posttreatment skeletal effects of rapid maxillary expansion
      investigated with low-dose computed tomography in growing subjects.
AB  - INTRODUCTION: The aim of this study was to use low-dose coronal computed
      tomography (CT) scans to evaluate the treatment and postretention effects of
      rapid maxillary expansion (RME) on the maxillary central incisors, midpalatal
      suture, and nasal cavity. METHODS: Multi-slice coronal CT scans of 17 subjects (7
      boys, 10 girls; mean age, 11.2 years) were taken before RME (T0), at the end of
      active expansion phase (T1), and after the retention period of 6 months (T2).
      Measurements were made on 3 coronal scans perpendicular to the occlusal plane and
      passing through anterior nasal spine (anterior scan), the midpoint between
      anterior nasal spine and posterior nasal spine (middle scan), and posterior nasal
      spine (posterior scan). Statistical analyses were performed with analysis of
      variance (ANOVA) for repeated measures with post-hoc tests. RESULTS: The
      transverse dimensions of the midpalatal suture and nasal cavity showed
      statistically significant T0 to T1 increments in all 3 coronal scans. The roots
      of the maxillary central incisors were more divergent than the crowns at both T1
      and T2. All T0-to-T1 measurements at the sutural and nasal levels decreased from
      the anterior to the posterior measurements. Between T1 and T2, all measurements
      exhibited statistically significant decreases with the exception of nasal width
      on the middle scan. CONCLUSIONS: When analyzed on coronal CT scans, the maxillary
      halves were separated by RME in a parallel manner and not in a triangular shape.
      At T2 after RME therapy, the suture appeared reorganized, and the expansion of
      the nasal cavity was stable.

PMID- 20816301
TI  - Distally displaced premolars: A dental anomaly associated with palatally
      displaced canines.
AB  - INTRODUCTION: The aim of this study was to evaluate the significance of
      association between distally displaced premolars (DDP) and palatally displaced
      canines (PDC) in the pattern of associated phenotypes of dental developmental
      disturbance. METHODS: A sample of 2811 subjects (mean age, 9 years 7 months +/- 1
      year 3 months) was divided randomly into 2 groups. The first group of 500
      subjects was the control group. The reference prevalence rates for the examined
      parameters were calculated for this group: DDP (measured with the distal angle
      theta and the premolar-molar angle gamma); PDC; and other dental anomalies,
      specifically, aplasia of the third molars, aplasia of the contralateral
      mandibular second premolar, aplasia of the maxillary lateral incisors, and small
      maxillary lateral incisors. Of the remaining 2311 subjects, the first 100 with a
      diagnosis of DDP of at least 1 mandibular second premolar comprised experimental
      group 1 (DDP group). In addition to sex distribution, the same variables that
      were examined in the control group were analyzed. In the subgroup with the
      concurrent DDP and PDC (experimental group 2, or DDP-PDC group), the presence of
      other dental anomalies was investigated. The prevalence rate for PDC in
      experimental group 1 was compared with that in the control group. The same was
      done for the prevalence rates for the 4 other dental anomalies in the PDC-DDP
      group (experimental group 2) vs the prevalence rates for these anomalies in the
      control group. All comparisons were performed with chi-square tests with the
      Yates correction (P <0.05), as were the comparisons between the sexes in
      experimental groups 1 and 2. The values for theta and gamma angles in
      experimental group 1 were compared with the values for these angles in
      experimental group 2, as well as with those in the control group. These
      statistical comparisons were made with analysis of variance (ANOVA) with the
      Bonferroni post-hoc test (P <0.05). RESULTS: The prevalence rate for PDC in
      experimental group 1 (28%) was significantly greater than in the control group
      (4.2%) (P <0.01). Significantly greater prevalence rates for aplasia of the
      second premolars, aplasia of the maxillary lateral incisors, and small maxillary
      lateral incisors were found in the PDC-DDP group (experimental group 2) compared
      with the control group. Significant sex differences (P <0.01) were found in both
      experimental groups. CONCLUSIONS: A significant relationship between distal
      displacement of unerupted mandibular second premolars and PDC was found. Because
      DDP is diagnosed earlier than PDC, it can be a developmental risk indicator for
      displaced maxillary permanent canines.

PMID- 20816302
TI  - Clinical study of frontal chewing patterns in various crossbite malocclusions.
AB  - INTRODUCTION: The purpose of this study was to clarify the frontal chewing
      patterns of various crossbite malocclusions. METHODS: A mandibular kinesiograph
      was used to record the masticatory movements of 106 subjects (ages, 12-35 years)
      with crossbite malocclusion and 22 subjects (ages, 16-30 years) with normal
      occlusion. The chewing patterns were classified into 8 chewing types according to
      the cycle shape of the frontal incisor point movement. The crossbite subjects
      were divided into 5 groups by the anteroposterior position of the crossbite, and
      then the subjects with posterior crossbite were divided into 3 groups by the
      transverse position of the crossbite. The Mann-Whitney U test was used to compare
      the frequency of each chewing type between any crossbite group and the control
      group; and between the various crossbite groups. RESULTS: In the crossbite
      groups, normal chewing occurred much less often than in subjects with normal
      occlusion. In the posterior crossbite group, reverse chewing was greater (P =
      0.002), and normal chewing was less frequent (P = 0.001) compared with the
      anterior crossbite group. When accompanied by mandibular shift, mandibular
      prognathism, arch crossbite, in the crossbite or shift side, reverse type, and
      reverse-crossing type occurred more often than in contralateral side.
      CONCLUSIONS: In the frontal plane, patients with posterior crossbite might have
      more abnormal chewing types than those with anterior crossbite, and posterior
      crossbite could contribute to the high frequency of reverse and reverse-crossing
      chewing types, especially when accompanied by mandibular shift, mandibular
      prognathism, or arch crossbite.

PMID- 20816303
TI  - Measurement of friction forces between stainless steel wires and "reduced
      friction" self-ligating brackets.
AB  - INTRODUCTION: In this study, we assessed the friction forces between various self
      ligating brackets and stainless steel orthodontic wires, subjected to different
      shear and bending forces in the buccolingual plane. METHODS: Three kinds of self
      ligating brackets and 2 kinds of ligated controls were tested in a newly
      developed in-vitro system. Friction was tested with stainless steel orthodontic
      wire in 3 deflection states. The Bonferroni multiple comparisons test was applied
      to evaluate intergroup differences (P <0.05). Wire samples were examined with a
      scanning electron microscope before and after sliding. RESULTS: The results
      showed significant intergroup differences in friction resistance in response to
      wire deflection. In nonzero buccolingual deflections, passive self-ligating
      brackets developed higher friction forces, comparable with those in the
      conventional elastic ligation control group. The control brackets with reduced
      friction ligature had considerably lower friction forces than any other group.
      The active self-ligating bracket ranked between the self-ligating brackets and
      the reduced friction ligature group. A tribologic survey showed substantial
      surface alterations among wire samples coupled with passive self-ligating
      brackets. CONCLUSIONS: In contrast to manufacturers' claims, this study
      illustrates that, in certain clinical situations, a firm passive bracket clip can
      have a negative influence on the wire-bracket frictional characteristics.

PMID- 20816304
TI  - Applicability of the Moyers mixed dentition probability tables and new prediction
      aids for a contemporary population in India.
AB  - INTRODUCTION: The Moyers mixed dentition space analysis method is among the most
      commonly used in clinical practice for detecting tooth size-arch length
      discrepancies. In view of reported secular trends, racial, and sex differences in
      tooth sizes, the purposes of this study were to evaluate the applicability of
      Moyers probability tables in a contemporary orthodontic population of India and
      to formulate more accurate mixed dentition prediction aids. METHODS: Odontometric
      data were collected from 300 male and 300 female subjects of Indian descent, who
      had fully erupted mandibular permanent incisors and maxillary and mandibular
      canines and premolars. We measured the mesiodistal crown widths with vernier
      scale dial calipers. The odontometric values obtained were then subjected to
      statistical and linear regression analysis. RESULTS: All tooth groups showed
      significant differences (P <0.001) between mesiodistal widths of male and female
      subjects. Regression equations for the maxillary arch (males, Y = 7.15 + 0.67X;
      females, Y = 7.44 + 0.65X) and the mandibular arch (males, Y = 5.55 + 0.71X;
      females, Y = 6.15 + 0.67X) were used to develop new probability tables on the
      Moyers pattern. Significant differences (P <0.05) were found between our
      predicted widths and the Moyers tables at almost all percentile levels, including
      the recommended 75% and 50% levels. CONCLUSIONS: We believe that these new
      prediction aids could be considered for a more precise mixed dentition space
      analysis in Indian children.

PMID- 20816305
TI  - Short-root anomaly in an orthodontic patient.
AB  - Short-root anomaly is a rare condition, but it can be a problem for orthodontists
      and their patients. Our aim in this article was to report the treatment of an
      orthodontic patient with short-root anomaly, highlighting the diagnostic aspects
      involved and the strategy used.

PMID- 20816306
TI  - Mucoepidermoid carcinoma diagnosed in orthodontic patients.
AB  - A detailed clinical examination is important for early diagnosis of oral lesions
      in every dental specialty, including orthodontics, particularly because these
      patients are constantly checked during orthodontic treatment. This report
      describes 2 men receiving orthodontic treatment and who had swelling on the hard
      palate diagnosed as mucoepidermoid carcinoma. Both patients received appropriate
      treatment and had a good prognosis because of the rapid recognition of these oral
      lesions by their orthodontists.

PMID- 20816307
TI  - Multidisciplinary approach for a patient with dentinogenesis imperfecta and
      anterior trauma.
AB  - Dentinogenesis imperfecta is an inherited dentinal dysplasia involving several
      risks for orthodontic treatment. This case report describes the multidisciplinary
      treatment of a 17-year-old girl whose Class II Division 1 malocclusion was
      complicated by dentinogenesis imperfecta type II and maxillary anterior trauma.

PMID- 20816309
TI  - Litigation, legislation, and ethics: Calling it quits.

PMID- 20816308
TI  - Three-dimensional surgical simulation.
AB  - In this article, we discuss the development of methods for computer-aided jaw
      surgery, which allows us to incorporate the high level of precision necessary for
      transferring virtual plans into the operating room. We also present a complete
      computer-aided surgery system developed in close collaboration with surgeons.
      Surgery planning and simulation include construction of 3-dimensional surface
      models from cone-beam computed tomography, dynamic cephalometry, semiautomatic
      mirroring, interactive cutting of bone, and bony segment repositioning. A virtual
      setup can be used to manufacture positioning splints for intraoperative guidance.
      The system provides further intraoperative assistance with a computer display
      showing jaw positions and 3-dimensional positioning guides updated in real time
      during the surgical procedure. The computer-aided surgery system aids in dealing
      with complex cases with benefits for the patient, with surgical practice, and for
      orthodontic finishing. Advanced software tools for diagnosis and treatment
      planning allow preparation of detailed operative plans, osteotomy repositioning,
      bone reconstructions, surgical resident training, and assessing the difficulties
      of the surgical procedures before the surgery. Computer-aided surgery can make
      the elaboration of the surgical plan a more flexible process, increase the level
      of detail and accuracy of the plan, yield higher operative precision and control,
      and enhance documentation of cases.

PMID- 20816310
TI  - Introduction to the special issue on the technology of radiotherapy.

PMID- 20816311
TI  - Synergies that work: evolution, epidemiology, and new insights.

PMID- 20816312
TI  - Change in human social behavior in response to a common vaccine.
AB  - PURPOSE: The purpose of this study was to test the hypothesis that exposure to a
      directly transmitted human pathogen-flu virus-increases human social behavior
      presymptomatically. This hypothesis is grounded in empirical evidence that
      animals infected with pathogens rarely behave like uninfected animals, and in
      evolutionary theory as applied to infectious disease. Such behavioral changes
      have the potential to increase parasite transmission and/or host solicitation of
      care. METHODS: We carried out a prospective, longitudinal study that followed
      participants across a known point-source exposure to a form of influenza virus
      (immunizations), and compared social behavior before and after exposure using
      each participant as his/her own control. RESULTS: Human social behavior does,
      indeed, change with exposure. Compared to the 48 hours pre-exposure, participants
      interacted with significantly more people, and in significantly larger groups,
      during the 48 hours immediately post-exposure. CONCLUSIONS: These results show
      that there is an immediate active behavioral response to infection before the
      expected onset of symptoms or sickness behavior. Although the adaptive
      significance of this finding awaits further investigation, we anticipate it will
      advance ecological and evolutionary understanding of human-pathogen interactions,
      and will have implications for infectious disease epidemiology and prevention.

PMID- 20816313
TI  - Does self-rated health mean the same thing across socioeconomic groups? Evidence
      from biomarker data.
AB  - PURPOSE: Self-rated health (SRH) is widely used to study health inequalities by
      socioeconomic status (SES), but concern has arisen that SRH may not correspond to
      objective health in the same way for different SES groups. We test whether levels
      of biological risk differ by SES for those with the same SRH. METHODS: We
      analyzed a U.S. nationally representative sample of 13,877 adults aged 25 to 80
      years. We tested whether education modifies the association between SRH and 14
      biomarkers representing metabolic, cardiovascular, inflammatory, and organ
      function using both interaction models and models stratified by four levels of
      SRH. Estimated education coefficients in the stratified models indicated whether
      biomarker levels varied by educational attainment within a given self-rated
      health category. RESULTS: Significant variation in biological risk by education
      within the same self-rated health category was found, especially at higher levels
      of SRH. In general, respondents with more education had healthier levels of
      biomarkers for the same level of SRH. CONCLUSIONS: The results suggest that the
      relation of self-reported health to objective health, as measured by biological
      risk factors, differs by socioeconomic status. Caution should be exercised when
      using SRH to compare health risks across SES groups.

PMID- 20816314
TI  - Incorporating individual-level distributions of exposure error in epidemiologic
      analyses: an example using arsenic in drinking water and bladder cancer.
AB  - PURPOSE: Epidemiologic analyses traditionally rely on point estimates of exposure
      for assessing risk despite exposure error. We present a strategy that produces a
      range of risk estimates reflecting distributions of individual-level exposure.
      METHODS: Quantitative estimates of exposure and its associated error are used to
      create for each individual a normal distribution of exposure estimates which is
      then sampled using Monte Carlo simulation. After the exposure estimate is
      sampled, the relationship between exposure and disease is evaluated; this process
      is repeated 99 times generating a distribution of risk estimates and confidence
      intervals. This is demonstrated in a bladder cancer case-control study using
      individual-level distributions of exposure to arsenic in drinking water. RESULTS:
      Sensitivity analyses indicate similar performance for categorical or continuous
      exposure estimates, and that increases in exposure error translate into a wider
      range of risk estimates. Bladder cancer analyses yield a wide range of possible
      risk estimates, allowing quantification of exposure error in the association
      between arsenic and bladder cancer, typically ignored in conventional analyses.
      CONCLUSIONS: Incorporating distributions of individual-level exposure error
      results in a more nuanced depiction of epidemiologic findings. This approach can
      be readily adopted by epidemiologists assuming distributions of individual-level
      exposure.

PMID- 20816315
TI  - Long-term health experience of jet engine manufacturing workers: IV. A comparison
      of central nervous system cancer ascertainment using mortality and incidence
      data.
AB  - PURPOSE: To compare ascertainment of central nervous system (CNS) neoplasms with
      the use of mortality and incidence data as part of an occupational epidemiology
      study. METHODS: Deaths were identified by matching the cohort of 223,894 jet
      engine manufacturing employees to the U.S. Social Security Administration death
      files and the National Death Index. Incident cancer cases were identified by
      matching the cohort to 19 state cancer registries. RESULTS: We identified 718
      cases overall: 59% by the use of both mortality and cancer incidence tracing; 24%
      by the use of only mortality tracing, and 17% by the use of only cancer incidence
      tracing. Compared with state cancer registries, death certificates missed 38% of
      the malignant, more than six times the benign and nearly 1.5 times the
      unspecified CNS cases. The positive predictive value of death certificates, with
      cancer registry as gold standard, was 6% for unspecified, 35% for benign, and 86%
      for malignant histologies. CONCLUSIONS: Death certificates seriously
      underascertained benign and unspecified CNS tumors; analyses determined with
      mortality data would not accurately capture the true extent of disease among the
      cohort. Most state cancer registries have only collected nonmalignant CNS tumor
      information since 2004, which currently limits the usefulness of state cancer
      registries as a source of nonmalignant CNS tumor identification.
      Underascertainment of CNS deaths could seriously affect interpretation of
      results, more so if examining nonmalignant CNS.

PMID- 20816316
TI  - Computer-aided system of evaluation for population-based all-in-one service
      screening (CASE-PASS): from study design to outcome analysis with bias
      adjustment.
AB  - PURPOSE: Population-based routine service screening has gained popularity
      following an era of randomized controlled trials. The evaluation of these service
      screening programs is subject to study design, data availability, and the precise
      data analysis for adjusting bias. We developed a computer-aided system that
      allows the evaluation of population-based service screening to unify these
      aspects and facilitate and guide the program assessor to efficiently perform an
      evaluation. METHODS: This system underpins two experimental designs: the posttest
      only non-equivalent design and the one-group pretest-posttest design and
      demonstrates the type of data required at both the population and individual
      levels. Three major analyses were developed that included a cumulative mortality
      analysis, survival analysis with lead-time adjustment, and self-selection bias
      adjustment. We used SAS AF software to develop a graphic interface system with a
      pull-down menu style. RESULTS: We demonstrate the application of this system with
      data obtained from a Swedish population-based service screen and a population
      based randomized controlled trial for the screening of breast, colorectal, and
      prostate cancer, and one service screening program for cervical cancer with Pap
      smears. The system provided automated descriptive results based on the various
      sources of available data and cumulative mortality curves corresponding to the
      study designs. The comparison of cumulative survival between clinically and
      screen-detected cases without a lead-time adjustment are also demonstrated. The
      intention-to-treat and noncompliance analysis with self-selection bias
      adjustments are also shown to assess the effectiveness of the population-based
      service screening program. Model validation was composed of a comparison between
      our adjusted self-selection bias estimates and the empirical results on
      effectiveness reported in the literature. CONCLUSIONS: We demonstrate a computer
      aided system allowing the evaluation of population-based service screening
      programs with an adjustment for self-selection and lead-time bias. This is
      achieved by providing a tutorial guide from the study design to the data
      analysis, with bias adjustment.

PMID- 20816317
TI  - Imaging genetics: Progressing by leaps and bounds.

PMID- 20816318
TI  - Invited commentary.

PMID- 20816319
TI  - Preoperative thrombolysis and venoplasty affords no benefit in patency following
      first rib resection and scalenectomy for subacute and chronic subclavian vein
      thrombosis.
AB  - BACKGROUND: Axillosubclavian vein thrombosis, also known as Paget-Schroetter
      syndrome, is a rare presentation of thoracic outlet syndrome (TOS) representing
      approximately 5% of all cases. Conventional management consists of routine
      anticoagulation, operative decompression via first rib resection and scalenectomy
      (FRRS), and, recently, thrombolysis. The purpose of our study was to
      retrospectively review our experience with this condition and compare the
      effectiveness of preoperative endovascular intervention with thrombolysis and
      venoplasty to anticoagulation alone in those undergoing FRRS to preserve
      subclavian vein patency. METHODS: A retrospective review was conducted for all
      venous TOS patients from July 2003 to May 2009 from a prospectively maintained
      database. Preoperative clinic notes were reviewed to allow stratification into
      two groups. One group consisted of patients undergoing preoperative endovascular
      intervention with thrombolysis and venoplasty, while the other group consisted of
      patients managed medically with anticoagulation alone prior to FRSS. Operative
      notes, postoperative venograms, and postoperative duplex imaging results were
      reviewed for presence of recanalization, chronic nonocclusive thrombus, or
      continued occlusion. RESULTS: One hundred three patients had 110 FRRS for
      subclavian vein thrombosis (53 men, 50 women), seven of which had contralateral
      FRRS for thrombosis. The cohort averaged 31 years of age (range, 16-54 years)
      with an overall, mean follow-up time of 16 months (range, 1-52 months). Of the
      110 veins evaluated, 45 underwent endovascular intervention (thombolysis, with or
      without venoplasty) prior to FRRS, and at 1 year, 41 (91%) were patent with
      improvement of symptoms. In the 65 veins on anticoagulation alone, 59 (91%)
      ultimately were patent, with symptomatic improvement in all. Overall, 91%
      (100/110) of subclavian veins were patent in patients completing follow-up, were
      asymptomatic, and back to their previous active lifestyle. CONCLUSIONS:
      Preoperative endovascular intervention offered no benefit over simple
      anticoagulation prior to FRRS, since the use of thrombolysis prior to FRRS,
      regardless of need for postoperative venoplasty, had little impact on overall
      rates of patency. The optimal treatment algorithm may merely be routine
      anticoagulation for all effort thrombosis patients prior to FRRS followed by
      venography with venoplasty if needed. The role of thrombolysis for Paget
      Schroetter syndrome should be further investigated in randomized trials.

PMID- 20816321
TI  - Perioperative platelet and monocyte activation in patients with critical limb
      ischemia.
AB  - BACKGROUND: Patients with critical limb ischemia (CLI) have a high rate of
      adverse cardiovascular events, particularly when undergoing surgery. We sought to
      determine the effect of surgery and vascular disease on platelet and monocyte
      activation in vivo in patients with CLI. METHODS: An observational, cross
      sectional study was performed at a tertiary referral hospital in the southeast of
      Scotland. Platelet and monocyte activation were measured in whole blood in
      patients with CLI scheduled for infrainguinal bypass and compared with matched
      healthy controls, patients with chronic intermittent claudication, patients with
      acute myocardial infarction, and those undergoing arthroplasty (n = 30 per
      group). Platelet and monocyte activation were quantified using flow cytometric
      assessment of platelet-monocyte aggregation, platelet P-selectin expression,
      platelet-derived microparticles, and monocyte CD40 and CD11b expression. RESULTS:
      Compared with those with intermittent claudication, subjects with CLI had
      increased platelet-monocyte aggregates (41.7% +/- 12.2% vs 32.6% +/- 8.5%,
      respectively), platelet microparticles (178.7 +/- 106.9 vs 116.9 +/- 53.4), and
      monocyte CD40 expression (70.0% +/- 12.2% vs 52.4% +/- 15.2%; P < .001 for all).
      Indeed, these levels were equivalent (P-selectin, 4.4% +/- 2.0% vs 4.9% +/- 2.2%;
      P > .05) or higher (platelet-monocyte aggregation, 41.7% +/- 12.2% vs 33.6% +/-
      7.0%; P < .05; platelet microparticles, 178.7 +/- 106.9 vs 114.4 +/- 55.0/microL;
      P < .05) than in patients with acute myocardial infarction. All platelet and
      monocyte activation markers remained elevated throughout the perioperative period
      in patients with CLI (P < .01) but not those undergoing arthroplasty.
      CONCLUSIONS: Patients undergoing surgery for CLI have the highest level of in
      vivo platelet and monocyte activation, and these persist throughout the
      perioperative period. Additional antiplatelet therapy may be of benefit in
      protecting vascular patients with more severe disease during this period of
      increased risk.

PMID- 20816324
TI  - Regarding "long-term outcomes and resource utilization of endovascular versus
      open repair of abdominal aortic aneurysms in Ontario".

PMID- 20816325
TI  - Regarding "a closer look at meta-analyses of observational data".

PMID- 20816327
TI  - Regarding "preoperative statin therapy is associated with improved outcomes and
      resource utilization in patients undergoing aortic aneurysm repair".

PMID- 20816329
TI  - Structural and mechanistic insights into a novel non-competitive Kunitz trypsin
      inhibitor from Adenanthera pavonina L. seeds with double activity toward serine-
      and cysteine-proteinases.
AB  - Kunitz proteinase inhibitors are widely distributed in legume seeds, and some of
      them have the ability to inhibit two different classes of enzymes. In this
      report, novel insights into three-dimensional structure and action mechanism of
      ApKTI, an Adenanthera pavonina Kunitz trypsin inhibitor, were provided to shed
      some light on an unconventional non-competitive activity against trypsin and
      papain. Firstly, ApKTI was purified by two tandem-size molecular exclusion
      chromatography high resolutions, Sephacryl S-100 and Superose 12 10/300 GL.
      Purified ApTKI showed molecular mass of 22 kDa and higher affinity against
      trypsin in comparison to papain, while the bifunctional inhibitor presented lower
      inhibitory activity. Moreover, in vitro assays showed that ApKTI has two
      independent interaction sites, permitting simultaneous inhibition to both
      enzymes. Theoretical three-dimensional structures of ApTKI complexed to both
      target proteinases were constructed in order to determine interaction mode by
      using Modeller v9.6. Since the structure of no non-competitive Kunitz inhibitor
      has been elucidated, ApTKI-trypsin and ApTKI-papain docking were carried out
      using Hex v5.1. In silico experiments showed that the opposite inhibitor loop
      interacts with adjacent sites of trypsin (Arg(64), Ser(107), Arg(88) and
      Lys(108)) and papain (Gln(51), Asp(172) and Arg(173)), probably forming a ternary
      complex. Unusual residue substitutions at the proposed interface can explain the
      relative rarity of twin trypsin/papain inhibition. The predicted non-coincidence
      of trypsin and papain binding sites is completely different from that of
      previously proposed inhibitors, adding more information about mechanisms of non
      competitive plant proteinase inhibitors.

PMID- 20816330
TI  - The paradigm of life extension.

PMID- 20816331
TI  - Long-term care and the electronic medical record.

PMID- 20816332
TI  - End-of-life care in the nursing home.

PMID- 20816333
TI  - The tongue, oral hygiene, and prevention of pneumonia in the institutionalized
      elderly.

PMID- 20816334
TI  - A synopsis of phosphate disorders in the nursing home.
AB  - Elderly patients are at an increased risk of developing both hypophosphatemia and
      hyperphosphatemia. Renal insufficiency predisposes elderly patients to elevated
      serum concentrations of phosphate. On the other hand, poor dietary intake and
      loss of phosphorus in the urine can lead to deficiency states. It is well
      documented that hyperphosphatemia is correlated with an increase in morbidity and
      mortality as a result of vascular calcification. This article reviews the
      etiology, pathophysiology, symptoms, and treatment of hypophosphatemia and
      hyperphosphatemia.

PMID- 20816335
TI  - An analysis of the interactions between individual comorbidities and their
      treatments--implications for guidelines and polypharmacy.
AB  - BACKGROUND: With aging there is an increase in frailty and chronic disease
      leading to a potential increase in medication use. Most clinical trials have
      excluded old, frail individuals and have failed to take into account the effects
      of outcome interaction. METHODS AND RESULTS: In this article we provide a
      mathematical model demonstrating that comorbidities, including old age, interact
      with therapies, reducing their effectiveness. CONCLUSION: These findings question
      the validity of single disease guidelines in old persons or in persons with
      multiple chronic diseases.

PMID- 20816336
TI  - Cost, staffing and quality impact of bedside electronic medical record (EMR) in
      nursing homes.
AB  - OBJECTIVE: There is growing political pressure for nursing homes to implement the
      electronic medical record (EMR) but there is little evidence of its impact on
      resident care. The purpose of this study was to test the unique and combined
      contributions of EMR at the bedside and on-site clinical consultation by
      gerontological expert nurses on cost, staffing, and quality of care in nursing
      homes. METHODS: Eighteen nursing facilities in 3 states participated in a 4-group
      24-month comparison: Group 1 implemented bedside EMR, used nurse consultation;
      Group 2 implemented bedside EMR only; Group 3 used nurse consultation only; Group
      4 neither. Intervention sites (Groups 1 and 2) received substantial, partial
      financial support from CMS to implement EMR. Costs and staffing were measured
      from Medicaid cost reports, and staff retention from primary data collection;
      resident outcomes were measured by MDS-based quality indicators and quality
      measures. RESULTS: Total costs increased in both intervention groups that
      implemented technology; staffing and staff retention remained constant.
      Improvement trends were detected in resident outcomes of ADLs, range of motion,
      and high-risk pressure sores for both intervention groups but not in comparison
      groups. DISCUSSION: Implementation of bedside EMR is not cost neutral. There were
      increased total costs for all intervention facilities. These costs were not a
      result of increased direct care staffing or increased staff turnover.
      CONCLUSIONS: Nursing home leaders and policy makers need to be aware of on-going
      hardware and software costs as well as costs of continual technical support for
      the EMR and constant staff orientation to use the system. EMR can contribute to
      the quality of nursing home care and can be enhanced by on-site consultation by
      nurses with graduate education in nursing and expertise in gerontology.

PMID- 20816337
TI  - End-of-life care in nursing homes: the importance of CNA staff communication.
AB  - OBJECTIVE: Staff communication has been shown to influence overall nursing home
      (NH) performance. However, no empirical studies have focused specifically on the
      impact of CNA communication on end-of-life (EOL) care processes. This study
      examines the relationship between CNA communication and nursing home performance
      in EOL care processes. DESIGN: Secondary data analysis of 2 NH surveys conducted
      in 2006-2007. SETTING: One hundred seven nursing homes in New York State.
      PARTICIPANTS: Participants were 2636 CNAs and 107 directors of nursing (DON).
      MEASUREMENTS: The measures of EOL care processes-EOL assessment and care delivery
      (5-point Likert scale scores)-were obtained from survey responses provided by 107
      DONs. The measure of CNA communication was derived from survey responses obtained
      from 2636 CNAs. Other independent variables included staff education, hospice use
      intensity, staffing ratio, staff-resident ethnic overlap index, facility
      religious affiliation, and ownership. METHODS: The reliability and validity of
      the measures of EOL care processes and CNA communication were tested in the
      current study sample. Multivariate linear regression models with probability
      weights were used. The analysis was conducted at the facility level. RESULTS: We
      found better CNA communication to be significantly associated with better EOL
      assessment (P = .043) and care delivery (P = .098). Two potentially modifiable
      factors-staff education and hospice use intensity-were associated with NHs'
      performance in EOL care processes. Facilities with greater ethnic overlap between
      staff and residents demonstrated better EOL assessment (P = .051) and care
      delivery scores (P = .029). CONCLUSION: Better CNA communication was associated
      with better performance in EOL care processes. Our findings provide specific
      insights for NH leaders striving to improve EOL care processes and ultimately the
      quality of care for dying residents.

PMID- 20816338
TI  - Beyond CMS quality measure adjustments: identifying key resident and nursing home
      facility factors associated with quality measures.
AB  - OBJECTIVE: This quality improvement (QI) project was initiated to understand what
      differentiates nursing homes (NHs) that perform well on publicly reported Centers
      for Medicare and Medicaid Services (CMS) Quality Measures (QMs). The intent was
      to assist NH staff to direct QI efforts to positively impact QM rates. A key step
      was to determine if any resident or facility characteristics might account for
      some of the variability in QMs of high-risk pressure ulcers (HRPrUs), low-risk
      incontinence (LRI), and Activities of Daily Living (ADL) decline, beyond those
      already adjusted for by CMS. DESIGN: Observational Study. SETTING AND
      PARTICIPANTS: The setting was 147 NHs across 12 northeast states owned by 1 for
      profit, multifacility organization in 2006 and 2007. INTERVENTION: None
      MEASUREMENTS: Minimum Data Set (MDS), patient admission information, facility
      staffing metrics, and CMS QM data. RESULTS: Relationships of facility and
      resident characteristics to QMs were evaluated using regression analyses
      performed separately for 2006 and 2007. Among factors found consistently to be
      significant (P < or = .05) for HRPrUs were percent admissions with pressure
      ulcers and percent residents with end-stage disease. For LRI, there was
      significant association with percent residents readmitted and percent incontinent
      of bladder on admission. ADL decline showed significant associations with
      licensed nurse turnover and facilities in specific states. CONCLUSION: Several
      resident and facility factors were associated with QMs beyond those previously
      adjusted for by CMS. With introduction of MDS 3.0, we suggest further exploration
      of resident and facility factors identified in this study.

PMID- 20816339
TI  - Reflections of medical students regarding the care of geriatric patients in the
      continuing care retirement community.
AB  - OBJECTIVE: There is growing recognition that students training to provide care
      for older adults need to be trained in all settings where older adults receive
      care, including retirement communities. The purpose of this study was to allow
      medical students to see older patients living and participating in activities in
      the long-term care setting and examine the effects that this experience had on
      the students. METHODS: Medical students were assigned to write an open-ended
      reflection paper about a community health experience. Forty-eight students wrote
      their reflection papers on their experience in a continuing care retirement
      facility. Three independent reviewers examined these reflective narratives for
      common themes. RESULTS: After analyzing the students' narratives, 6 themes
      emerged: (1) The initial exposure to dementia, (2) confronting death and dying,
      (3) the diversity of care and services for the elderly, (4) the cost of care for
      the elderly, (5) seniors can lead active lives if given the opportunity, and (6)
      the rewards of the health care team-patient relationship. CONCLUSION: The
      students' reflective narratives provide valuable insights into how medical
      students view retirement communities, the physician's role in the care of
      geriatric patients, the importance of interdisciplinary health care, the cost of
      care for elderly patients, and their views on dementia and dying. Through this
      experience, students received valuable lessons about taking care of older adults
      in the community that their interactions with patients in the hospital and
      ambulatory medical offices had not provided.

PMID- 20816340
TI  - The complexity of implementing culture change practices in nursing homes.
AB  - PURPOSE: The culture change (CC) movement aims to transform the traditional
      nursing home (NH) that is institutional in design with hierarchical management
      structure into a homelike environment that empowers residents and frontline
      staff. This study examines differences in adoption of CC practices according to a
      NH's self-reported extent of CC implementation and its duration of CC adoption.
      Furthermore, it examines differences in adoption by whether a CC practice is
      considered less versus more complex, using complexity theory as the theoretical
      framework for this classification. DESIGN AND METHODS: Using data from a 2007
      Commonwealth-funded study, we analyzed a national sample of 291 US nursing homes
      that identified as being "for the most part" or "completely" CC facilities for "1
      to 3 years" or "3+ years." Also, using a complexity theory framework, we ranked
      16 practices commonly associated with CC as low, moderately, or highly complex
      based on level of agreement needed to actuate the process (number of parties
      involved) and the certainty of intended outcomes. We then examined the prevalence
      of CC-associated practices in relation to their complexity and the extent and
      duration of a NH's CC adoption. RESULTS: We found practices ranked as less
      complex were implemented more frequently in NHs with both shorter and longer
      durations of CC adoption. However, more complex CC practices were more prevalent
      among NHs reporting "complete" adoption for 3+ years versus 1 to 3 years. This
      was not observed in NHs reporting having CC "for the most part."
      CONCLUSIONS/IMPLICATIONS: Less complex practices may be more economical and
      easier to implement. These early successes may result in sufficient momentum so
      that more complex change can follow. A nursing home that more completely embraces
      the culture change movement may be more likely to attempt these complex changes.

PMID- 20816341
TI  - Psychoactive drugs as risk factors for functional decline among
      noninstitutionalized dependent elderly people.
AB  - OBJECTIVE: To analyze the association between use of psychoactive drugs and
      functional decline among noninstitutionalized dependent elderly people. DESIGN:
      Cross-sectional study. PARTICIPANTS: A total of 161 community-dwelling elderly
      people with functional dependence. MEASUREMENTS: The data were analyzed using
      logistic regression with adjustment for age models. The independent variables
      were the following: use of psychoactive drugs (antidepressants, anticonvulsants,
      anxiolytics, antipsychotics, or sedatives), cognitive decline (Mini-Mental State
      Examination score<20), and daytime sleepiness. The dependent variables were the
      following: dependence relating to activities of daily living (ADLs) and
      dependence relating to instrumental activities of daily living (IADLs). RESULTS:
      Data on 131 individuals of mean age 77.5 years were analyzed. Psychoactive drugs
      were used by 33.6%. Age-adjusted univariate analysis showed associations between
      psychoactive drug use and both ADLs and IADLs. However, in multivariate analysis,
      only ADLs showed a significant association with psychoactive drug use,
      independent of cognitive decline and daytime sleepiness (OR=2.67; 95% CI: 1.04
      6.85; P=.04). CONCLUSIONS: There is a greater risk of impairment of ADLs among
      noninstitutionalized elderly people using psychoactive drugs. These results
      indicate the need for rational use of medication groups among this population
      with greater risk of functional impairment.

PMID- 20816342
TI  - Flu in 15: a novel 15-minute education program to promote acceptance of the
      influenza vaccine among health care workers.
AB  - INTRODUCTION AND RATIONALE: A performance improvement project was undertaken to
      increase health care worker (HCW) influenza vaccination acceptance rates in the
      long-term care setting by using a novel 15-minute education intervention called
      the "Flu in 15." As a core principle, we taught that more Americans die from
      complications of influenza than hepatitis B, yet there remains individual
      reluctance and barriers to achieve high acceptance rates of influenza vaccination
      among HCWs. METHODS: During chance encounters we offered the Flu in 15 in-service
      to all HCWs at the Johns Hopkins Bayview Care Center including certified nursing
      assistants (also called geriatric nursing assistants), registered nurses,
      registered dieticians, environment staff, physical therapists, occupational
      therapists, speech therapists, respiratory therapists, social workers, and
      administrators. Of the 106 of 347 HCWs who participated in the Flu in 15 in
      service, 58 were by chance encounters selected to be surveyed based on
      convenience. We surveyed 68 of 241 HCWs who did not attend the Flu in 15 in
      service as a comparison. RESULTS: Of the 58 participants who were asked if the in
      service helped them understand why a flu vaccine is needed yearly, we found that
      15% responded "tremendously," 48% "a lot," 26% "some," 7% "a little," and 2%
      "no." We had 24% report that the program was effective in changing their behavior
      to accept the flu vaccination for the first time. We found that 49% responded
      that the in-service was effective in either changing their behavior to accept the
      flu vaccination for the first time or reaccept it if recently declined in
      previous years. With respect to motivation, 42% of the certified nursing
      assistants stated that the in-service made them think more about returning to
      school to get a license in some area of health care. Although not cause and
      effect, we observed an increase in the HCW acceptance rate of the influenza
      vaccine from 65% in 2006-2007 to 73% in 2007-2008. We noticed a decreased trend
      in patient deaths attributed to complications of influenza with 4 deaths in 2006
      2007 and no deaths in 2007-2008. CONCLUSIONS: The Flu in 15 in-service promoted a
      better understanding of the importance of the influenza vaccine and demonstrated
      an associated increase in HCW acceptance of the flu vaccine. Although we cannot
      claim cause and effect, we noted a decrease in resident mortality in the
      intervention year compared with the prior year. Now that some medical centers
      require yearly influenza vaccines among HCWs, the education component remains
      relevant to provide reason behind the mandate.

PMID- 20816343
TI  - End-of-life care in a PACE program: respecting the patient's wishes while
      supporting the caregiver.
AB  - Family caregivers play a key role at the end of life. They provide high levels of
      assistance and are often called on to make complex medical decisions. This is a
      period where there is potential for conflict, particularly when the patient lacks
      decision-making capacity. This case report describes how an interdisciplinary
      team helped an end-of-life caregiver to find closure while advocating for the
      patient's wishes to be carried out. The intervention of appropriate advanced care
      planning and frequent communication resulted in a positive outcome.

PMID- 20816344
TI  - Prevention of venous thromboembolism in long-term care: time for action?

PMID- 20816345
TI  - Mercury exposure and children's health. Foreword.

PMID- 20816347
TI  - Protein folding.

PMID- 20816348
TI  - Reevaluating obstructive sleep apnea as a risk factor for cerebrovascular
      disease.

PMID- 20816349
TI  - A cost-effectiveness analysis of carotid artery stenting compared with
      endarterectomy.
AB  - Endarterectomy and angioplasty with stenting have emerged as 2 alternative
      treatments for carotid artery stenosis. This study's objective was to determine
      the cost-effectiveness of carotid artery stenting (CAS) compared with carotid
      endarterectomy (CEA) in symptomatic subjects who are suitable for either
      intervention. A Markov analysis of these 2 revascularization procedures was
      conducted using direct Medicare costs (2007 US$) and characteristics of a
      symptomatic 70-year-old cohort over a lifetime. In the base case analysis, CAS
      produced 8.97 quality-adjusted life-years, compared with 9.64 quality-adjusted
      life-years for CEA. The incremental cost of stenting was $17,700, and thus CAS
      was dominated by CEA. Sensitivity analyses show that the long-term probabilities
      of major stroke or mortality influenced the results. In the base case analysis,
      CEA for patients with symptomatic stenosis has a greater benefit than CAS, with
      lower direct costs. With 59% probability, CEA will be the optimal intervention
      when all of the model assumptions are varied simultaneously.

PMID- 20816350
TI  - Editorial. Complications after a new surgical technique of coloured anterior
      chamber implants.

PMID- 20816346
TI  - Mercury exposure and children's health.
AB  - Acute or chronic mercury exposure can cause adverse effects during any period of
      development. Mercury is a highly toxic element; there is no known safe level of
      exposure. Ideally, neither children nor adults should have any mercury in their
      bodies because it provides no physiological benefit. Prenatal and postnatal
      mercury exposures occur frequently in many different ways. Pediatricians, nurses,
      and other health care providers should understand the scope of mercury exposures
      and health problems among children and be prepared to handle mercury exposures in
      medical practice. Prevention is the key to reducing mercury poisoning. Mercury
      exists in different chemical forms: elemental (or metallic), inorganic, and
      organic (methylmercury and ethyl mercury). Mercury exposure can cause acute and
      chronic intoxication at low levels of exposure. Mercury is neuro-, nephro-, and
      immunotoxic. The development of the child in utero and early in life is at
      particular risk. Mercury is ubiquitous and persistent. Mercury is a global
      pollutant, bio-accumulating, mainly through the aquatic food chain, resulting in
      a serious health hazard for children. This article provides an extensive review
      of mercury exposure and children's health.

PMID- 20816351
TI  - The American Surgical Education Association.

PMID- 20816352
TI  - Urgent carotid endarterectomy for crescendo transient ischemic attacks and stroke
      in-evolution: abstracted review.

PMID- 20816353
TI  - Hand-assisted laparoscopic sigmoid colectomy skills acquisition: augmented
      reality simulator versus human cadaver training models.
AB  - OBJECTIVE: The aim of this study was to compare a simulator with the human
      cadaver model for hand-assisted laparoscopic colorectal skills acquisition
      training. DESIGN: An observational prospective comparative study was conducted to
      compare the laparoscopic surgery training models. SETTING: The study took place
      during the laparoscopic colectomy training course performed at the annual
      scientific meeting of the American Society of Colon and Rectal Surgeons.
      PARTICIPANTS: Thirty four practicing surgeons performed hand-assisted
      laparoscopic sigmoid colectomy on human cadavers (n = 7) and on an augmented
      reality simulator (n = 27). Prior laparoscopic colorectal experience was
      assessed. Trainers and trainees completed independently objective structured
      assessment forms. Training models were compared by trainees' technical skills
      scores, events scores, and satisfaction. RESULTS: Prior laparoscopic experience
      was similar in both surgeon groups. Generic and specific skills scores were
      similar on both training models. Generic events scores were significantly better
      on the cadaver model. The 2 most frequent generic events occurring on the
      simulator were poor hand-eye coordination and inefficient use of retraction.
      Specific events were scored better on the simulator and reached the significance
      limit (p = 0.051) for trainers. The specific events occurring on the cadaver were
      intestinal perforation and left ureter identification difficulties. Overall
      satisfaction was better for the cadaver than for the simulator model (p = 0.009).
      CONCLUSIONS: With regard to skills scores, the augmented reality simulator had
      adequate qualities for the hand-assisted laparoscopic colectomy training.
      Nevertheless, events scores highlighted weaknesses of the anatomical replication
      on the simulator. Although improvements likely will be required to incorporate
      the simulator more routinely into the colorectal training, it may be useful in
      its current form for more junior trainees or those early on their learning curve.

PMID- 20816354
TI  - High-performance teams and the physician leader: an overview.
AB  - The complexity of health care delivery within the United States continues to
      escalate in an exponential fashion driven by an explosion of medical technology,
      an ever-expanding research enterprise, and a growing emphasis on evidence-based
      practices. The delivery of care occurs on a continuum that spans across multiple
      disciplines, now requiring complex coordination of care through the use of novel
      clinical teams. The use of teams permeates the health care industry and has done
      so for many years, but confusion about the structure and role of teams in many
      organizations contributes to limited effectiveness and suboptimal outcomes. Teams
      are an essential component of graduate medical education training programs. The
      health care industry's relative lack of focus regarding the fundamentals of
      teamwork theory has contributed to ineffective team leadership at the physician
      level. As a follow-up to our earlier manuscripts on teamwork, this article
      clarifies a model of teamwork and discusses its application to high-performance
      teams in health care organizations. Emphasized in this discussion is the role
      played by the physician leader in ensuring team effectiveness. By educating
      health care professionals on the fundamentals of high-performance teamwork, we
      hope to stimulate the development of future physician leaders who use proven
      teamwork principles to achieve the goals of trainee education and excellent
      patient care.

PMID- 20816355
TI  - Measuring surgical trainee perceptions to assess the operating room educational
      environment.
AB  - OBJECTIVE: To determine measurable differences in the perception of learning
      between junior and senior residents in the operating rooms of an obstetrics and
      gynecology (OBGYN) residency program. DESIGN, SETTING, AND PARTICIPANTS: Using a
      cross-sectional design, the Operating Room Educational Environment Measure
      (OREEM), a 40-item educational environment inventory, was administered to 28
      OBGYN residents from 1 training program, who train at 3 hospital sites. The OREEM
      measures a trainee's perceptions of the teaching surgeon, learning opportunities,
      operating room atmosphere, and workload. The primary outcome was total OREEM
      scores and secondary outcomes were OREEM subscale scores, global impression of
      education, and internal consistency and validity of the OREEM scale. Group sample
      sizes of 10 and 10 achieved 80% power to detect a 10% difference between group
      mean OREEM scores +/- 10% with a significance level of 0.05. RESULTS: Twenty-four
      residents including 11 junior (postgraduate years 1 and 2) and 13 senior
      (postgraduate years 3 and 4) residents were included in the analysis. Total OREEM
      scores, learning opportunities, and workload/support subscale scores were
      significantly lower for junior residents compared with senior residents across
      all sites. Perceptions of learning at a multispecialty tertiary referral hospital
      were lower than the community and regional hospitals. This was secondary to
      complexity of cases, subspecialty fellows, and decreased opportunities to first
      assist in the operating room. The OREEM demonstrated acceptable reliability and
      construct validity. CONCLUSIONS: There are measurable differences in perception
      of the operating room educational environment between junior and senior OBGYN
      residents using the reliable and valid Operating Room Educational Environment
      Measure.

PMID- 20816356
TI  - Teaching colorectal surgery in the laparoscopic era; is it safe?
AB  - OBJECTIVES: With the introduction of laparoscopic colorectal surgery, the
      question is raised as to whether laparoscopic colectomies can safely be performed
      by surgical registrars, when supervised by experienced laparoscopic surgeons. In
      this study we have compared surgical outcomes of surgical registrars, fellows,
      and staff surgeons in a Dutch teaching hospital. DESIGN, SETTING, AND
      PARTICIPANTS: Using a prospective database, the surgical outcomes of staff
      surgeons, fellows, and surgical registrars were compared. Pre- and postoperative
      complications were evaluated, including anastomotic failure. The percentage of
      reintervention, mortality, readmission, total hospital stay, and operating time
      were evaluated. The quality of the surgical resection was assessed by comparing
      the number of resected lymph nodes in malignant cases and the percentage of
      patients with adequate resection margins. RESULTS: Analysis was performed in 420
      patients. The majority of surgery was performed by staff surgeons. Outcomes of
      surgery for staff surgeons, fellows, and surgical registrars were comparable with
      respect to complications, percentage of conversions, and oncological adequacy.
      CONCLUSIONS: Comprehensive training as a colorectal surgeon should include
      competence in laparoscopic resections. Our results show that laparoscopic
      colorectal surgery can safely be performed by surgical registrars with no
      increase of the number of conversions to laparotomy or the number of
      complications.

PMID- 20816357
TI  - Tensile strength of a surgeon's or a square knot.
AB  - OBJECTIVE: To test the integrity of surgeon's knots and flat square knots using 4
      different suture materials. STUDY DESIGN: Chromic catgut, polyglactin 910, silk,
      and polydioxanone sutures were tied in the 2 types of knot configurations. For
      all sutures, a 0-gauge United States Pharmacopeia suture was used. Knots were
      tied by a single investigator (J.B.). The suture was soaked in 0.9% sodium
      chloride for 60 s and subsequently transferred to a tensiometer where the tails
      were cut to 3-mm length. We compared the knots, measuring knot strength with a
      tensiometer until the sutures broke or untied. RESULTS: A total of 119 throws
      were tied. We found no difference in mean tension at failure between a surgeon's
      knot (79.7 N) and a flat square knot (82.9 N). Using a chi(2) test, we did not
      find a statistically significant difference in the likelihood of knots coming
      untied between surgeon's knots (29%) and flat square knots (38%). CONCLUSIONS:
      Under laboratory conditions, surgeon's knots and flat square knots did not differ
      in tension at failure or in likelihood of untying.

PMID- 20816358
TI  - Presacral epidermoid cyst in a male: a case report and literature review.
AB  - Presacral cysts are an uncommon entity most often found incidentally in women.
      These tumors can arise from any of the 1 or more cell lines present in the
      presacral space during embryogenesis. We present a case of a 46-year-old male
      patient who was found to have a well-circumscribed presacral mass on computed
      tomography (CT) scan, which was obtained for his complaint of vague lower back
      pain. He underwent transabdominal excision, and pathology revealed a presacral
      epidermoid cyst filled with keratinaceous material. Presacral cysts are rare,
      especially in male patients. These tumors originate from an embryologic error
      during development. Because of the risk of infection and malignant
      transformation, they should be excised. Surgical options include a posterior
      approach, transabdominal approach, combined approach, or transrectal approach.
      The approach is dictated by the tumor size, location, presence of malignancy, and
      bony invasion.

PMID- 20816359
TI  - Left-handedness--a handicap for training in surgery?
AB  - BACKGROUND: Left-handedness was historically considered a disability and a social
      stigma, and teachers would make efforts to suppress it in their students. Little
      data are available on the impact of left-handedness on surgical training. This
      report reviews available data on this subject. METHODS: We did systematic
      electronic and manual literature searches using a predetermined strategy
      independently by 2 investigators, 1 left- and 1 right-handed, to identify reports
      on surgical training and left-handedness. RESULTS: The review revealed 19 studies
      on the subject of left-handedness and surgical training. Data were heterogeneous
      and based mostly on surveys. Left-handedness produced anxiety in residents and
      their trainers. There was a lack of mentoring on laterality. Surgical
      instruments, both conventional and laparoscopic, are not adapted to left-handed
      use and require ambilaterality training from the resident. There is significant
      pressure to change hand laterality during training. However, left-handedness
      might present an advantage in operations involving situs inversus or left lower
      limb operations. CONCLUSIONS: Left-handedness is a challenge both for the trainee
      and the trainer in surgery. Early laterality-related mentoring in medical school
      and during surgical residency with provision of left-handed instruments might
      reduce the inconveniences of left-handed surgeons learning.

PMID- 20816360
TI  - Trends of surgical career selection among medical students and graduates: a
      global perspective.
AB  - BACKGROUND: Declining trends in surgery have been well-researched in the North
      American region, but little is known about the international dynamics affecting
      this phenomenon. A comprehensive approach to this emerging issue is lacking.
      OBJECTIVES: Our objective in this study is to explore global trends related to
      medical student interest in surgical careers. We will also identify factors
      influencing the choice of surgery as a career and outline practical interventions
      to nurture interest in these fields, as described in the literature. DESIGN: We
      present a focused review of worldwide trends of surgical career selection among
      medical students of geographically distant and diverse sociocultural backgrounds.
      A systematic literature search was performed using PubMed. The studies were
      conducted over the last fifteen years with the study populations scattered over 6
      continents. RESULTS: North American studies have shown a declining trend for
      medical students to select surgery as a career, but a recent recovery has been
      observed. However, surgery is still the popular choice of career among Middle
      Eastern and Far-Eastern Asian men. Sociocultural variants and personal
      satisfaction are likely influential factors with financial rewards being the
      least significant. Surgery is also popular in Nigeria despite their increased
      awareness of risk of HIV/AIDS associated with surgery. A decline in surgery has
      been observed in Australia, New Zealand, and South Africa. Medical students and
      graduates of Greece, Switzerland, and the UK mostly prefer nonsurgical careers.
      Multiple extrinsic and intrinsic factors appear to play a role for such a
      phenomenon. Specific interventions are now being used to create a rebound effect
      for such a declining trend observed in most of the regions worldwide.
      CONCLUSIONS: Global trends show a variation of interest in surgery as a career
      option throughout the 6 continents. Possible factors affecting this phenomenon
      are similar among geographically distant and diverse student cultures.

PMID- 20816361
TI  - Establishment of American College of Surgeons-accredited Education Institutes:
      the dawn of a new era in surgical education and training.

PMID- 20816362
TI  - Marcia and Eugene Applebaum Surgical Learning Center.

PMID- 20816363
TI  - The Simulation and Skills Center at Beth Israel Deaconess Medical Center.

PMID- 20816364
TI  - Canadian Surgical Technologies and Advanced Robotics.

PMID- 20816365
TI  - Carolinas Simulation Center.

PMID- 20816366
TI  - Centre of Excellence For Simulation Education and Innovation (CESEI).
AB  - Simulation is becoming an integral part of medical education. The American
      College of Surgeons (ACS) was the first organization to recognize the value of
      simulation-based learning, and to award accreditation for educational
      institutions that aim to provide simulation as part of the experiential learning
      opportunity. Centre of Excellence for Simulation Education and Innovation (CESEI)
      is a multidisciplinary and interprofessional educational facility that is based
      at the University of British Columbia (UBC) and Vancouver Costal Health Authority
      (VCH). Centre of Excellence for Simulation Education and Innovation's goal is to
      provide excellence in education, research, and healthcare delivery by providing a
      technologically advanced environment and learning opportunity using simulation
      for various groups of learners including undergraduate, postgraduate, nursing,
      and allied health professionals. This article is an attempt to describe the
      infrastructure, services, and uniqueness of the Centre of Excellence for
      Simulation Education and Innovation.

PMID- 20816367
TI  - Improving access to surgery in a developing country: experience from a surgical
      collaboration in Sierra Leone.
AB  - BACKGROUND: Although surgery is increasingly recognized as an essential component
      of primary health care, there has been little documentation of surgical programs
      in low- and middle-income countries. Surgeons OverSeas (SOS) is a New York-based
      organization with a mission to save lives in developing countries by improving
      surgical care. This article highlights the surgical program in Sierra Leone as a
      possible model to improve access to surgery. METHODS: An SOS team conducted a
      needs assessment of surgical capacity in Sierra Leone in February 2008.
      Interventions were then developed and programs were implemented. A follow-up
      assessment was conducted in December 2009, which included interviews of key
      Sierra Leone hospital personnel and a review of operating room log books.
      RESULTS: Based on an initial needs assessment, a program was developed that
      included training, salary support, and the provision of surgical supplies and
      equipment. Two 3-day workshops were conducted for a total of 44 health workers,
      salary support given to over 100 staff, and 2 containers of supplies and
      equipment were donated. Access to surgery, as measured by the number of major
      operations at Connaught Hospital, increased from 460 cases in 2007 to 768 cases
      in 2009. CONCLUSIONS: The SOS program in Sierra Leone highlights a method for
      improving access to surgery that incorporates an initial needs assessment with
      minimal external support and local staff collaboration. The program functions as
      a catalyst by providing training, salary support, and supplies. The beneficial
      results of the program can then be used to advocate for additional resources for
      surgery from policy makers. This model could be beneficial in other resource-poor
      countries in which improved access to surgery is desired.

PMID- 20816368
TI  - Consensus statement on the adoption of the Committee on Publication Ethics (COPE)
      guidelines.

PMID- 20816369
TI  - When the evidence is weak, caution should be applied.

PMID- 20816370
TI  - S-1 for advanced colorectal cancer: do we need another oral fluorouracil prodrug?

PMID- 20816371
TI  - Testicular haemangiomas and vascular malformations.

PMID- 20816372
TI  - Safety of denosumab in giant-cell tumour of bone.

PMID- 20816373
TI  - Cyanine dyes in optical imaging of tumours.

PMID- 20816374
TI  - Regulation of circadian rhythms and hypothalamic-pituitary-adrenal axis: an
      overlooked interaction in cancer.

PMID- 20816375
TI  - Angiotensin-receptor blockade, cancer, and concerns.

PMID- 20816376
TI  - Angiotensin-receptor blockade, cancer, and concerns.

PMID- 20816377
TI  - Angiotensin-receptor blockade, cancer, and concerns.

PMID- 20816378
TI  - Angiotensin-receptor blockade, cancer, and concerns.

PMID- 20816379
TI  - Angiotensin-receptor blockade, cancer, and concerns.

PMID- 20816381
TI  - The sentinel-node concept: a dramatic improvement in breast-cancer surgery.

PMID- 20816382
TI  - Potential coexistence of both bacterial and eukaryotic small RNA biogenesis and
      functional related protein homologs in Archaea.
AB  - RNA silencing plays crucial roles in both bacteria and eukaryotes, yet its
      machinery appears to differ in these two kingdoms. A couple of Argonaute protein
      homologs have been reported in some archaeal species in recent years. As
      Argonaute protein is the key component of eukaryotic RNA silencing pathways, such
      findings suggested the possibility of existence of eukaryotic RNA silencing like
      pathways in Archaea, which present the life forms between prokaryotes and
      eukaryotes. To further explore such hypothesis, we systematically screened 71
      fully sequenced archaeal genomes, and identified some proteins containing
      homologous regions to the functional domains of eukaryotic RNA silencing pathway
      key proteins. The phylogenetic relationships of these proteins were analyzed. The
      conserved functional amino acids between archaeal and eukaryotic Piwi domains
      suggested their functional similarity. Our results provide new clues to the
      evolution of RNA silencing pathways.

PMID- 20816383
TI  - Epistatic effect between ACACA and FABP2 gene on abdominal fat traits in
      broilers.
AB  - Epistasis is generally defined as the interaction between two or more genes or
      their mRNA or protein products to influence a single trait. Experimental evidence
      suggested that epistasis could be important in the determination of the genetic
      architecture of complex traits in domestic animals. Acetyl-coenzyme A carboxylase
      alpha (ACACA) and fatty acid binding protein 2 (FABP2) are both key factors of
      lipogenesis and transport. They may play a crucial role in the weight variability
      of abdominal adipose tissue in the growing chicken. In this study, the
      polymorphisms of c.2292G>A in ACACA and c.-561A>C in FABP2 were detected among
      individuals from two broiler lines which were divergently selected for abdominal
      fat content. Epistasis between the two SNPs on abdominal fat weight (AFW) and
      abdominal fat percentage (AFP) was analyzed. The additive x additive epistatic
      components between these two SNPs were found significant or suggestively
      significant on both AFW and AFP in lean lines of the 9th and 10th generation;
      whereas, it was not significantly associated with either AFW or AFP in fat lines.
      At the same time, there were not any other significant epistatic components found
      in both generations or in both lines. Significant epistatic effects between these
      two SNPs found only in the lean lines could partly be due to the fact that the
      abdominal fat traits in these two experimental lines have been greatly modified
      by strong artificial selection. The results suggested that the epistasis mode may
      be different between the lean and fat chicken lines. Our results could be helpful
      in further understanding the genetic interaction between candidate genes
      contributing to phenotypic variation of abdominal fat content in broilers.

PMID- 20816384
TI  - Expression of the Tribolium castaneum (Coleoptera: Tenebrionidae) hsp83 gene and
      its relation to oogenesis during ovarian maturation.
AB  - Heat shock proteins (HSP) can protect organisms and cells from thermal damage. In
      this study, we cloned the full length cDNA encoding the HSP83 protein (the
      homologue of HSP90) of Tribolium castaneum (red flour beetle). The isolated cDNA
      contains the full coding sequence, a partial 5' untranslated region of 55 bp and
      the complete 3' untranslated region. We found the hsp83 gene is located on
      chromosome 5 of the T. castaneum genome. The predicted HSP83 protein sequence has
      a high similarity (on average 86.77%) with that of other insect species. The
      expression of the hsp83 gene in the whole body and in the ovary could be induced
      with heat stress (40 degrees for 1 h) in newly hatched (within 3 h post
      emergence) and mature (10 days post emergence) beetles. Under normal conditions,
      the hsp83 expression in the ovary is about 3-fold higher than in the whole body
      at both stages. No significant difference in hsp83 expression was observed
      between the two ovarian developmental stages regardless if the beetles were
      treated with heat shock or not. The expression of the HSP83 protein in the whole
      body could also be induced with heat stress in newly hatched and mature beetles.
      However, in the ovary, HSP83 was only expressed in the follicle cells of mature
      beetles and not in newly hatched beetles, regardless if the beetles were treated
      with heat shock or not. Furthermore, the females were not able to produce mature
      oocytes after knock-down of the hsp83 expression by injecting dsRNA. These
      results suggest that the HSP83 protein is involved in protection against heat
      stress and could be involved in oogenesis during ovarian maturation of T.
      castaneum.

PMID- 20816385
TI  - Mapping of qGL7-2, a grain length QTL on chromosome 7 of rice.
AB  - A residual heterozygous line (RHL) carrying a heterozygous segment between two
      SSR loci RM11 and RM134 on the rice chromosome 7 was selected from a set of
      recombinant inbred lines from the cross D50 (javanica)/HB277 (indica). The former
      parent produces much longer grains than the latter. Selfed progenies of this
      selection were analyzed genotypically (SSRs) and phenotypically (grain length).
      Grain length was discontinuously variable in the mapping populations, allowing
      for the placement of this QTL qGL7-2 within a approximately 4.8 cM interval
      defined by RM351 and RM234. A set of new markers within this region were
      developed, which narrowed the QTL to a 278 kb region defined by the markers
      Indel1 and RM21945. This region contains 49 predicted genes. The results also
      suggest that the novel allele for grain length will be used for the application
      of marker assisted selection for the improvement of grain length.

PMID- 20816386
TI  - Novel pleiotropic loci controlling panicle architecture across environments in
      japonica rice (Oryza sativa L.).
AB  - To identify quantitative trait loci (QTLs) controlling panicle architecture in
      japonica rice, a genetic map was constructed based on simple sequence repeat
      (SSR) markers and 254 recombinant inbred lines (RILs) derived from a cross
      between cultivars Xiushui 79 and C Bao. Seven panicle traits were investigated
      under three environments. Single marker analysis indicated that a total of 27 SSR
      markers were highly associated with panicle traits in all the three environments.
      Percentage of phenotypic variation explained by single locus varied from 2% to
      35%. Based on the mixed linear model, a total of 40 additive QTLs for seven
      panicle traits were detected by composite interval mapping, explaining 1.2%-35%
      of phenotypic variation. Among the 9 QTLs with more than 10% of explained
      phenotypic variation, two QTLs were for the number of primary branches per
      panicle (NPB), two for panicle length (PL), two for spikelet density (SD), one
      for the number of secondary branches per panicle (NSB), one for secondary branch
      distribution density (SBD), and one for the number of spikelets per panicle (NS),
      respectively. qPLSD-9-1 and qPLSD-9-2 were novel pleiotropic loci, showing
      effects on PL and SD simultaneously. qPLSD-9-1 explained 34.7% of the phenotypic
      variation for PL and 25.4% of the phenotypic variation for SD, respectively.
      qPLSD-9-2 explained 34.9% and 24.4% of the phenotypic variation for PL and SD,
      respectively. The C Bao alleles at the both QTLs showed positive effects on PL,
      and the Xiushui 79 alleles at the both QTLs showed positive effects on SD.
      Genetic variation of panicle traits are mainly attributed to additive effects.
      QTL x environment interactions were not significant for additive QTLs and
      additive x additive QTL pairs.

PMID- 20816387
TI  - Identification of genomic regions determining flower and pod numbers development
      in soybean (Glycine max L.).
AB  - Flower and pod numbers per plant are important agronomic traits underlying
      soybean yield. So far quantitative trait loci (QTL) detected for flower and pod
      related traits have mainly focused on the final stage, and might therefore have
      ignored genetic effects expressed during a specific developmental stage. Here,
      dynamic expressions of QTL for flower and pod numbers were identified using 152
      recombinant inbred lines (RILs) and a linkage map of 306 markers. Wide genetic
      variation was found among RILs; 17 unconditional and 18 conditional QTL were
      detected for the two traits at different developmental stages over two years.
      Some QTL were detected only at one stage and others across two or more stages,
      indicating that soybean flower and pod numbers development may be governed by
      time-dependent gene expression. Three main QTL (qfn-Chr18-2, qfn-Chr20-1, and qfn
      Chr19) were detected for flower number, and two main QTL (qpn-Chr11 and qpn
      Chr20) were detected for pod number. The phenotypic variation explained by them
      ranged from 6.1% to 34.7%. The markers linked to these QTL could be used in
      marker-assisted selection for increasing soybean flower and pod numbers, with the
      ultimate aim of increasing soybean yield. Comparison of the QTL regions for
      flower and pod numbers traits with the related genes reported previously showed
      that seven and four related genes were located in the QTL regions of qfn-Chr11
      and qfn-Chr19, respectively. These results provide a basis for fine mapping and
      cloning of flower and pod development-related genes.

PMID- 20816388
TI  - A special issue on immunology and cell biology of protozoa.

PMID- 20816389
TI  - [Cardiovascular morbidity and mortality and electrocardiographic criteria of left
      ventricular hypertrophy in hypertensive patients treated in primary care].
AB  - FUNDAMENTALS AND OBJECTIVE: Electrocardiographic voltage criteria are the
      preferred method for diagnosis of left ventricular hypertrophy (LVH) in Primary
      Health Care (PHC). Several of these have been described as major adverse
      cardiovascular events (MACE) predictors. The aim of this study was to analyse the
      relationship between MACE occurrence in a cohort of hypertensive subjects in PHC
      and different electrocardiographic criteria recorded. PATIENTS AND METHODS: 265
      hypertensive subjects attending PHC were randomly selected and followed up for 12
      years. Standard 12-lead electrocardiograms were recorded at the beginning of the
      study. The occurrence of ischemic heart disease, heart failure, stroke,
      peripheral vascular disease, arrhythmia or cardiovascular death was considered as
      MACE. Electrocardiographic voltage criteria recorded were: Sokolow-Lyon,
      Minnesota code 3.1, Gubner and Ungerleider, Cornell voltage and Schillaci and
      Dalfo modifications. Data were analyzed using the life-table method and Cox
      regression models. RESULTS: 14,3% of patients lost to follow-up showed no
      differences in baseline characteristics from the rest of the cohort. The median
      follow-up was 10.1 years (IQR: 5.8-12.0). The cumulative survival rate was 53.5%
      (95% CI, 45.7-61.3%). The incidence of MACE was 5.85 (95% CI, 4.73-6.97) per 100
      hypertensive patients-year. In the multivariate analysis none of the ECG criteria
      showed statistical association with the occurrence of MACE. CONCLUSIONS: No
      association has been found between different electrocardiographic LVH criteria
      and the incidence of MACE in a cohort of hypertensive patients followed-up in a
      PHC setting for 12 years.

PMID- 20816390
TI  - Current Topics in Developmental Biology. Notch signalling. Prologue.

PMID- 20816391
TI  - Notch: the past, the present, and the future.
AB  - Proliferating investigations of the Notch pathway have given rise to the Notch
      "field," which has grown exponentially over the past 30 years. This field,
      founded by investigations of embryology and genetics in Drosophila, now
      encompasses many metazoa, including humans. The increasingly diverse scope of the
      field has engendered an expanding understanding that normal Notch pathway
      function is central to most developmental decision-making in animals, and that
      pathway dysfunction is implicated in many diseases, including cancer. We provide
      a personal view of the foundations and rapid evolution of the Notch field; and we
      discuss a variety of outstanding conundrums and questions regarding Notch
      biology, for which answers will be found and refined during the next 30 years.

PMID- 20816392
TI  - Mechanistic insights into Notch receptor signaling from structural and
      biochemical studies.
AB  - Notch proteins are the receptors in a highly conserved signal transduction system
      used to communicate signals between cells that contact each other. Studies
      investigating structure-function relationships in Notch signaling have gained
      substantial momentum in recent years. Here, we summarize the current
      understanding of the molecular logic of Notch signal transduction, emphasizing
      structural and biochemical studies of Notch receptors, their ligands, and
      complexes of intracellular Notch proteins with their target transcription
      factors. Recent advances in the structure-based modulation of Notch-signaling
      activity are also discussed.

PMID- 20816394
TI  - Roles of glycosylation in Notch signaling.
AB  - Notch and the DSL Notch ligands Delta and Serrate/Jagged are glycoproteins with a
      single transmembrane domain. The extracellular domain (ECD) of both Notch
      receptors and Notch ligands contains numerous epidermal growth factor (EGF)-like
      repeats which are post-translationally modified by a variety of glycans.
      Inactivation of a subset of genes that encode glycosyltransferases which initiate
      and elongate these glycans inhibits Notch signaling. In the formation of
      developmental boundaries in Drosophila and mammals, in mouse T-cell and marginal
      zone B-cell development, and in co-culture Notch signaling assays, the regulation
      of Notch signaling by glycans is to date a cell-autonomous effect of the Notch
      expressing cell. The regulation of Notch signaling by glycans represents a new
      paradigm of signal transduction. O-fucose glycans modulate the strength of Notch
      binding to DSL Notch ligands, while O-glucose glycans facilitate juxta-membrane
      cleavage of Notch, generating the substrate for intramembrane cleavage and Notch
      activation. Identifying precisely how the addition of particular sugars at
      specific locations on Notch modifies Notch signaling is a challenge for the
      future.

PMID- 20816396
TI  - Gamma-secretase and the intramembrane proteolysis of Notch.
AB  - Gamma-secretase is the crucial proteolytic activity that releases the Notch
      intracellular domain and is therefore a central player in the canonical Notch
      signaling transduction pathway. We discuss here briefly the discovery of gamma
      secretase and what is known on its structure and function. Recent work also
      indicates that the assembly and activity of gamma-secretase might be regulated by
      novel cell biological mechanisms. Finally we explore the recent insight that
      there are several gamma-secretase complexes in mammalian and discuss
      possibilities to use gamma-secretase as a drug target in Alzheimer's disease and
      cancer.

PMID- 20816393
TI  - Canonical and non-canonical Notch ligands.
AB  - Notch signaling induced by canonical Notch ligands is critical for normal
      embryonic development and tissue homeostasis through the regulation of a variety
      of cell fate decisions and cellular processes. Activation of Notch signaling is
      normally tightly controlled by direct interactions with ligand-expressing cells,
      and dysregulated Notch signaling is associated with developmental abnormalities
      and cancer. While canonical Notch ligands are responsible for the majority of
      Notch signaling, a diverse group of structurally unrelated noncanonical ligands
      has also been identified that activate Notch and likely contribute to the
      pleiotropic effects of Notch signaling. Soluble forms of both canonical and
      noncanonical ligands have been isolated, some of which block Notch signaling and
      could serve as natural inhibitors of this pathway. Ligand activity can also be
      indirectly regulated by other signaling pathways at the level of ligand
      expression, serving to spatiotemporally compartmentalize Notch signaling activity
      and integrate Notch signaling into a molecular network that orchestrates
      developmental events. Here, we review the molecular mechanisms underlying the
      dual role of Notch ligands as activators and inhibitors of Notch signaling.
      Additionally, evidence that Notch ligands function independent of Notch is
      presented. We also discuss how ligand posttranslational modification,
      endocytosis, proteolysis, and spatiotemporal expression regulate their signaling
      activity.

PMID- 20816397
TI  - Two opposing roles of RBP-J in Notch signaling.
AB  - RBP-J/Su(H)/Lag1, the main transcriptional mediator of Notch signaling, binds DNA
      with the consensus sequence YRTGDGAD. Notch target genes can be controlled by two
      opposing activities of RBP-J. The interaction of the Notch intracellular domain
      with RBP-J induces a weak transcriptional activation and requires an additional
      tissue-specific transcriptional activator such as bHLH proteins or GATA to
      mediate strong target gene expression. For example, during Drosophila sensory
      organ precursor (SOP) cell development, proneural bHLH interacts with Da, a
      Drosophila orthologue of E2A, to form a tissue-specific activator of Su(H), the
      Drosophila orthologue of RBP-J. This complex and Su(H) act synergistically to
      promote the epidermal cell fate. In contrast, a complex of Su(H) with Hairless, a
      Drosophila functional homologue of MINT, has transcriptional repression activity
      that promotes SOP differentiation to neurons. Recent conditional loss-of-function
      studies demonstrated that transcriptional networks involving RBP-J, MINT, and E2A
      are conserved in mammalian cell differentiation, including multiple steps of
      lymphocyte development, and probably also in neuronal maturation in adult
      neurogenesis. During neurogenesis, Notch-RBP-J signaling was thought historically
      to be involved mainly in the maintenance of undifferentiated neural progenitors.
      However, the identification of a tissue-specific transcriptional activator of RBP
      J-Notch has revealed new roles of RBP-J in the promotion of neuronal maturation.
      Finally, the Notch-independent function of RBP-J was recently discovered and will
      be reviewed here.

PMID- 20816395
TI  - Endocytosis and intracellular trafficking of Notch and its ligands.
AB  - Notch signaling occurs through direct interaction between Notch, the receptor,
      and its ligands, presented on the surface of neighboring cells. Endocytosis has
      been shown to be essential for Notch signal activation in both signal-sending and
      signal-receiving cells, and numerous genes involved in vesicle trafficking have
      recently been shown to act as key regulators of the pathway. Defects in vesicle
      trafficking can lead to gain- or loss-of-function defects in a context-dependent
      manner. Here, we discuss how endocytosis and vesicle trafficking regulate Notch
      signaling in both signal-sending and signal-receiving cells. We will introduce
      the key players in different trafficking steps, and further illustrate how they
      impact the signal outcome. Some of these players act as general factors and
      modulate Notch signaling in all contexts, whereas others modulate signaling in a
      context-specific fashion. We also discuss Notch signaling during mechanosensory
      organ development in the fly to exemplify how endocytosis and vesicle trafficking
      are effectively used to determine correct cell fates. In summary, endocytosis
      plays an essential role in Notch signaling, whereas intracellular vesicle
      trafficking often plays a context-dependent or regulatory role, leading to
      divergent outcomes in different developmental contexts.

PMID- 20816398
TI  - Notch targets and their regulation.
AB  - The proteolytic cleavages elicited by activation of the Notch receptor release an
      intracellular fragment, Notch intracellular domain, which enters the nucleus to
      activate the transcription of targets. Changes in transcription are therefore a
      major output of this pathway. However, the Notch outputs clearly differ from cell
      type to cell type. In this review we discuss current understanding of Notch
      targets, the mechanisms involved in their transcriptional regulation, and what
      might underlie the activation of different sets of targets in different cell
      types.

PMID- 20816400
TI  - Ultradian oscillations in Notch signaling regulate dynamic biological events.
AB  - Notch signaling regulates many dynamic processes; accordingly, expression of
      genes in this pathway is also dynamic. In mouse embryos, one dynamic process
      regulated by Notch is somite segmentation, which occurs with a 2-h periodicity.
      This periodic event is regulated by a biological clock called the segmentation
      clock, which involves cyclic expression of the Notch effector gene Hes7. Loss of
      Hes7 expression and sustained expression of Hes7 result in identical and severe
      somite defects, suggesting that Hes7 oscillation is required for proper somite
      segmentation. Mathematical models of this oscillator have been used to generate
      and test hypothesis, helping to uncover the role of negative feedback in
      regulating the oscillator. Oscillations of another Notch effector gene, Hes1,
      plays an important role in maintenance of neural stem cells. Hes1 expression
      oscillates with a period of about 2-3h in neural stem cells, whereas sustained
      Hes1 expression inhibits proliferation and differentiation of these cells,
      suggesting that Hes1 oscillations are important for their proper activities. Hes1
      inhibits its own expression as well as the expression of the proneural gene
      Neurogenin2 and the Notch ligand Delta1, driving oscillations of these two genes.
      Delta1 oscillations in turn maintain neural stem cells by mutual activation of
      Notch signaling, which re-activates Hes1 to close the cycle. Hes1 expression also
      oscillates in embryonic stem (ES) cells. Cells expressing low and high levels of
      Hes1 tend to differentiate into neural and mesodermal cells, respectively.
      Furthermore, Hes1-null ES cells display early and uniform neural differentiation,
      indicating that Hes1 oscillations act to promote multipotency by generating
      heterogeneity in both the differentiation timing and the fate choice. Taken
      together, these results suggest that Notch signaling can drive short-period
      oscillatory expression of Hes7 and Hes1 (ultradian oscillation) and that
      ultradian oscillations are important for many biological events.

PMID- 20816399
TI  - Notch signaling in the vasculature.
AB  - Notch signaling is an evolutionarily conserved, intercellular signaling mechanism
      that plays myriad roles during vascular development and physiology in
      vertebrates. These roles include the regulation of arteriovenous specification
      and differentiation in both endothelial cells and vascular smooth muscle cells,
      regulation of blood vessel sprouting and branching during normal and pathological
      angiogenesis, and the physiological responses of vascular smooth muscle cells.
      Defects in Notch signaling also cause inherited vascular diseases, such as the
      degenerative vascular disorder cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy. This review summarizes recent
      studies that highlight the multiple roles the Notch signaling pathway plays
      during vascular development and physiology.

PMID- 20816401
TI  - Notch signaling in cardiac development and disease.
AB  - The Notch-signaling pathway is involved in multiple processes during vertebrate
      cardiac development. Cardiomyocyte differentiation, patterning of the different
      cardiac regions, valve development, ventricular trabeculation, and outflow tract
      development have all been shown to depend on the activity of specific Notch
      signaling elements. From these studies, it becomes obvious that Notch regulates
      in a cell autonomous or non-cell autonomous manner different signaling pathways,
      pointing to a role for Notch as a signal coordinator during cardiogenesis. While
      most of the research has concentrated on Notch signaling in the myocardium, the
      importance of Notch activity in the cardiac endothelium (endocardium) must not be
      overlooked. Endocardial Notch activity is crucial for valve and ventricular
      trabeculae development, two processes that illustrate the role of Notch as a
      signal coordinator. The importance of Notch signaling in human disease is evident
      from the discovery that many mutations in components of this pathway segregate in
      several inherited and acquired disorders. This reflects the fundamental roles
      that Notch performs during cardiac ontogeny. This review examines the
      experimental evidence supporting a role for Notch in cardiac development and
      adult heart homeostasis, and how dysregulated Notch signaling may lead to cardiac
      disease in the newborn and in the adult.

PMID- 20816402
TI  - Notch signaling in the regulation of stem cell self-renewal and differentiation.
AB  - Stem cells are rare and unique precursor cells that participate in the building
      and rebuilding of tissues and organs during embryogenesis, postnatal growth, and
      injury repair. Stem cells are distinctively endowed with the ability to both self
      renew and differentiate, such that they can replenish the stem cell pool while
      continuing to produce the differentiated daughter cells that are essential for
      tissue function. Stem cell self-renewal/differentiation decisions must be
      carefully controlled during organogenesis, tissue homeostasis, and regeneration,
      as failure in stem cell maintenance or activation can lead to progressive tissue
      wasting, while unchecked self-renewal is a hallmark of many cancers. Here, we
      review evidence implicating the Notch signaling pathway, an evolutionarily
      conserved cell fate determinant with widespread roles in a variety of tissues and
      organisms, as a crucial regulator of stem cell behavior. As discussed below, this
      pathway plays varied and critical roles at multiple stages of organismal
      development, in lineage-specific differentiation of pluripotent embryonic stem
      cells, and in controlling stem cell numbers and activity in the context of age
      related tissue degeneration, injury-induced tissue repair, and malignancy.

PMID- 20816403
TI  - Notch signaling in solid tumors.
AB  - In recent years a substantial body of evidence derived from not only preclinical
      but also clinical studies has accumulated in support of Notch signaling playing
      important oncogenic roles in several types of cancer. The finding that activating
      Notch mutations are frequently found in patients suffering from acute
      lymphoblastic leukemia is one of the best examples for a critical role of Notch
      signaling in cancer, a fact that motivated many researchers and clinicians to
      study the role of Notch also in solid tumors. Hence Notch signaling has gained
      increasing attention as a potential therapeutic target. In this book chapter we
      would like to discuss our current knowledge of Notch signaling within different
      types of solid cancers as well as advantages and disadvantages of potential new
      therapies that try to target the oncogenic properties of Notch signaling.

PMID- 20816404
TI  - Biodiversity and noncanonical Notch signaling.
AB  - Early genetics in flies revealed that Notch is a complex pleiotropic locus. We
      now know that Notch is a receptor that plays prominent roles during development
      and functions locally in many tissues to instruct cell fate decisions. Drosophila
      has been an excellent model to identify genetically the elements that contribute
      to the canonical Notch signaling transduction machinery defined as DSL-Notch-CSL
      MAML axis. This core pathway is required in many biological events in all
      animals. Though the canonical Notch pathway is relatively simple, and as the
      steps of the events are now more deeply understood, an increasing number of
      reports in the last decade show that many other molecules can influence Notch
      signaling, some by competing with a given element of the cascade. This may occur
      at any step bringing more diversity and plasticity to the Notch pathway. Most of
      these regulatory molecules act in a context-specific manner and/or are themselves
      key regulators in other pathways, providing increasing examples of how
      connections among distinct pathway modulate each other ("cross talk"). The
      noncanonical signals discussed in this chapter are broadly defined and correspond
      to the following: DSL-independent activations, interactions with non-DSL ligands,
      CSL-independent signaling, signal transduction without cleavage, differential
      posttranslational modifications, competition/protection for a cofactor, and cross
      talk with other signaling pathways [Wnt, bone morphogenic protein (BMP), NF
      kappaB, etc.]. Though some deemed controversial, these events may impact human
      diseases. Understanding the molecular nature of these events will allow avoidance
      of adverse effects during possible clinical treatments. In this review, we will
      focus on some noncanonical Notch activities and their in vivo significance during
      developmental and pathological processes.

PMID- 20816405
TI  - Headache. Preface.

PMID- 20816406
TI  - Headache. Foreword.

PMID- 20816407
TI  - Epidemiology of headache.
AB  - Epidemiological studies conducted in the general population point to average
      headache prevalence rates of 46% for 1-year prevalence and of 64% for lifetime
      prevalence. For migraine, most studies conducted in the adult general population
      of western Europe and North America indicate rates between 5% and 9% in men, and
      between 12% and 25% in women. Non-western countries report lower figures.
      Migraine shows no gender differences in children, while in the elderly its
      frequency appears much reduced in both genders. About one-third of migraineurs
      suffer from migraine with aura. For tension-type headache, prevalence data
      reports in the literature are few and conflicting: rates range from 11% in
      Singapore to 20-40% in the USA and over 80% in Denmark. It is worth noting that
      the highest figures are found in studies where a personal interview has been
      employed. This probably indicates that the prevalence of this headache subtype is
      particularly sensitive to the method of data collection. Cluster headache occurs
      in 1-3 per thousand of the general population, with a gender (M:F) ratio of about
      3:1. About 4% of the adult general population suffers from chronic daily
      headache.

PMID- 20816408
TI  - The social impact and burden of headache.

PMID- 20816409
TI  - Biological sciences related to headache.
AB  - Headache can occur as a result of activation of pain-sensitive cranial
      structures, such as the dura mater, vasculature, and the cranial and cervical
      muscles and ligaments, which are innervated by primary afferent neurons
      originating from the trigeminal and dorsal root ganglia of the upper cervical
      spinal nerves. Similar to general nociceptive sensation, C fibers and Adelta
      fibers are known to play an important role in headache perception. Findings from
      nerve stimulation studies indicate that C fibers transmit aching, throbbing, or
      burning pain that builds up slowly, whereas the Adelta fibers conduct sharper
      initial pain sensation. These primary afferent nerve fibers transmit nociceptive
      information from the pain-sensitive endings in the cranial structures through the
      trigeminal and first and second spinal dorsal root ganglia to the brainstem at
      the pontine level. The nociceptive fibers then project to the central pain
      conducting pathways at the spinal trigeminal nucleus. In this chapter, we discuss
      the anatomy in relation to headache, including the meninges, dural sinuses, blood
      vessels, sensory ganglia, cranial and neck muscles, and the central pain
      conducting pathways.

PMID- 20816411
TI  - Biological science of headache channels.
AB  - Several episodic neurological diseases, including familial hemiplegic migraine
      (FHM) and different types of epilepsy, are caused by mutations in ion channels,
      and hence classified as channelopathies. The classification of FHM as a
      channelopathy has introduced a new perspective in headache research and has
      strengthened the idea of migraine as a disorder of neural excitability. Here we
      review recent studies of the functional consequences of mutations in the CACNA1A
      and SCNA1A genes (encoding the pore-forming subunit of Ca(V)2.1 and Na(V)1.1
      channels) and the ATPA1A2 gene (encoding the alpha(2) subunit of the Na(+)/K(+)
      pump), responsible for FHM1, FHM3, and FHM2, respectively. These studies show
      that: (1) FHM1 mutations produce gain-of-function of the Ca(V)2.1 channel and, as
      a consequence, increased glutamate release at cortical synapses and facilitation
      of induction and propagation of cortical spreading depression (CSD); (2) FHM2
      mutations produce loss-of-function of the alpha(2) Na(+)/K(+)-ATPase; and (3) the
      FHM3 mutation accelerates recovery from fast inactivation of Na(V)1.5 channels.
      These findings are consistent with the hypothesis that FHM mutations share the
      ability to render the brain more susceptible to CSD, by causing excessive
      synaptic glutamate release (FHM1) or decreased removal of K(+) and glutamate from
      the synaptic cleft (FHM2) or excessive extracellular K(+) (FHM3).

PMID- 20816412
TI  - Genetics of headaches.
AB  - Insight into the molecular mechanisms involved in primary headaches is important
      to identify drug targets for improving treatment of patients, but essentially
      lacking. Genetic research is increasingly successful in pinpointing these
      mechanisms. Most progress has been made for Familial Hemiplegic Migraine, a rare
      subtype of migraine with aura. Three genes (CACNA1A, ATP1A2 and SCN1A) have been
      identified that all encode ion transporters. Cellular and transgenic mouse
      studies suggest that neuronal hyperexcitability and increased susceptibility to
      cortical spreading depression, the correlate of migraine aura, are important
      molecular mechanisms in migraine. Investigating monogenic diseases in which
      migraine is a prominent feature such as CADASIL, which is caused by mutations in
      the NOTCH3 gene, can help understanding the pathology of migraine. Candidate gene
      association studies and linkage studies in the common forms of migraine were less
      successful. Except for the MTHFR gene no gene variant has been identified yet.
      Convincingly demonstrated genetic findings in other primary headaches such as
      cluster headache and tension-type headache are even rarer. However, with current
      technical possibilities of massive genotyping and international efforts to
      collect large well-phenotyped patient cohorts, the first gene variants for
      various primary headache types are likely to be discovered in the coming decade.

PMID- 20816414
TI  - Experimental models of migraine.
AB  - In vitro studies on animal and human cephalic vessels allow the measurement of
      second messengers or intracellular calcium concentrations and the evaluation of
      the role of endogenous neuropeptides in perivascular nerve endings involved in
      migraine pathophysiology. In addition, in vitro human models allow the assessment
      of receptorial cranial selectivity and the collection of reliable information
      regarding the behavior of these vessels in migraine headache. The availability of
      animal models of migraine has favoured impressive advances in understanding the
      mechanisms and mediators underlying migraine attacks, as well as the development
      of new and more specific therapeutic agents. The trigeminovascular system (TVS)
      has emerged as a critical efferent component, and the mediators of its activity
      have been identified and characterized, as have some of the receptors involved.
      The similarity of the trigeminal innervation across species has made it possible
      to draw conclusions on the neurophysiological responses to electrical or chemical
      stimulation of the trigeminal fibers. Studies involving substances known to
      induce migraine-like attacks, i.e., nitric oxide (NO) donors, have provided
      interesting insights into the central nuclei probably involved in the initiation
      and repetition of migraine attacks. The neuronal and vascular effects of such
      substances might yield an increasing body of evidence for a better understanding
      of the pathophysiology of migraine attacks.

PMID- 20816413
TI  - The neurobiology of migraine.
AB  - The understanding of migraine has moved well beyond its traditional
      characterization as a "vascular headache." In considering the basic neurobiology
      of migraine, it is important to begin with the concept of migraine as not merely
      a headache, but rather a heterogeneous array of episodic symptoms. Among the
      array of phenomena experienced by migraine patients are visual disturbances,
      nausea, cognitive dysfunction, fatigue, and sensitivity to light, sound, smell,
      and touch. These symptoms may occur independently or in any combination, and in
      some patients occur even in the absence of headache. The diversity and
      variability of symptoms experienced by migraine patients belies a complex
      neurobiology, involving multiple cellular, neurochemical, and neurophysiological
      processes occurring at multiple neuroanatomical sites. Migraine is a multifaceted
      neurobiological phenomenon that involves activation of diverse neurochemical and
      cellular signaling pathways in multiple regions of the brain. Propagated waves of
      cellular activity in the cortex, possibly involving distinct glial and vascular
      signaling mechanisms, can occur along with activation of brainstem centers and
      nociceptive pathways. Whether different brain regions become involved in a linear
      sequence, or as parallel processes, is uncertain. The modulation of brain
      signaling by genetic factors, and by sex and sex hormones, provides important
      clues regarding the fundamental mechanisms by which migraine is initiated and
      sustained. Each of these mechanisms may represent distinct therapeutic targets
      for this complex and commonly disabling disorder.

PMID- 20816410
TI  - Pharmacology.
AB  - Headache treatment has been based primarily on experiences with non-specific
      drugs such as analgesics, non-steroidal anti-inflammatory drugs, or drugs that
      were originally developed to treat other diseases, such as beta-blockers and
      anticonvulsant medications. A better understanding of the basic
      pathophysiological mechanisms of migraine and other types of headache has led to
      the development over the past two decades of more target-specific drugs. Since
      activation of the trigeminovascular system and neurogenic inflammation are
      thought to play important roles in migraine pathophysiology, experimental studies
      modeling those events successfully predicted targets for selective development of
      pharmacological agents to treat migraine. Basically, there are two fundamental
      strategies for the treatment of migraine, abortive or preventive, based to a
      large degree on the frequency of attacks. The triptans, which exhibit potency
      towards selective serotonin (5-hydroxytryptamine, 5-HT) receptors expressed on
      trigeminal nerves, remain the most effective drugs for the abortive treatment of
      migraine. However, numerous preventive medications are currently available that
      modulate the excitability of the nervous system, particularly the cerebral
      cortex. In this chapter, the pharmacology of commercially available medications
      as well as drugs in development that prevent or abort headache attacks will be
      discussed.

PMID- 20816415
TI  - Management of headache patients.
AB  - Headache is a very common complaint, in both primary care and in specialist
      settings. Headache patients account for around 20% of all outpatients seen in
      neurological practices and their management, particularly when they present with
      intractable headache, or are suspected of having secondary headaches, can be a
      challenge for the clinician. All the guidelines agree that the diagnosis of
      headache is merely clinical and that testing is not recommended if the individual
      is not significantly more likely than anyone else in the general population to
      have a significant abnormality. A full history of the temporal profile of the
      headache should be gathered first: when it first started, the circumstances of
      its onset, whether it has remained the same over time, and, if not, in what way
      it has changed. The patient should be questioned carefully about the specific
      characteristics of the attacks (frequency, duration, severity of the pain,
      efficacy of the treatments). It is also necessary to establish whether there is a
      history of other diseases and to investigate gynecological and psychological
      history, and family history. History alone allows a diagnosis of probable primary
      headache. Signs of a possible secondary headache must be carefully sought in all
      patients, even in apparently clear-cut cases. The guidelines recommend careful
      investigation of new headaches or those whose features have recently changed in
      order to exclude secondary headache. Once a secondary headache has been
      reasonably ruled out, it can help the patient to investigate possible comorbid
      pathologies and suggest appropriate lifestyle changes.

PMID- 20816416
TI  - Headache diaries and calendars.
AB  - Headache is one of the most common types of pain and, in the absence of
      biological markers, headache diagnosis depends only on information obtained from
      clinical interviews and physical and neurological examinations. Headache diaries
      make it possible to record prospectively the characteristics of every attack and
      the use of headache calendars is indicated for evaluating the time pattern of
      headache, identifying aggravating factors, and evaluating the efficacy of
      preventive treatment. This may reduce the recall bias and increase accuracy in
      the description. The use of diagnostic headache diaries does have some
      limitations because the patient's general acceptance is still limited and some
      subjects are not able to fill in a diary. In this chapter, we consider diaries
      and calendars specially designed for migraine and, in particular, aim to: (1)
      determine what instruments are available in clinical practice for diagnosis and
      follow-up of treatments; and (2) describe the tools that have been developed for
      research and their main applications in the headache field. In addition, we
      include information on diaries available online and proposals for future areas of
      research.

PMID- 20816417
TI  - Implementing the International Classification of Headache Disorders, 2nd edition
      (ICHD-II).

PMID- 20816418
TI  - Triggers of migraine and tension-type headache.
AB  - Identification of trigger factors or precipitants is frequently recommended as a
      basic strategy in the treatment of migraine and tension-type headache (TTH).
      Trigger factors increase the probability of headache in the short term. Potential
      trigger factors have been examined most frequently in migraine and less often in
      TTH. Many of these factors are related to migraine as well as to TTH, but their
      prevalence may differ in the two headache types. In this chapter, we will review
      the findings of retrospective as well as of prospective and controlled studies.
      Taken together, virtually all aspects of life have been suspected to trigger
      migraine or TTH, but scientific evidence for many of these triggers is poor.
      Menstruation has a prominent unfavorable role in migraine and possibly in TTH.
      There is at least some evidence that environmental factors such as weather,
      lights, noise and odors, stress and other psychological factors, sleeping
      problems, fatigue and tiredness may play a role. In addition, intake of alcohol,
      caffeine withdrawal, skipping meals, and possibly dehydration may trigger
      migraine and TTH in some patients. Scientific evidence is lacking that any other
      food or food additive plays a relevant role as a trigger factor of headaches.

PMID- 20816419
TI  - Acute headache in the emergency department.
AB  - In the acute setting, the primary objective is to decide whether the headache is
      primary, secondary but benign (for example a headache associated with a cold), or
      secondary to a potentially life-threatening cause (subarachnoid hemorrhage (SAH),
      bacterial meningitis, intracranial hypertension). The cornerstone of headache
      diagnosis is the interview with the patient, followed by a thorough physical
      examination. These two first clinical steps determine the need for investigation,
      immediate with inpatient care or on an outpatient basis, and the treatment to
      recommend, acutely and for future attacks in the case of primary headache. The
      indication for referral to a neurologist for long-term follow-up is assessed.
      Headaches can be separated into four groups: (1) recent onset and thunderclap;
      (2) recent onset with progressive installation: (3) well known to the patient and
      episodic (attacks with headache-free periods, as in episodic migraine or cluster
      headache); and (4) chronic daily headaches (more than 3 months, more than 15 days
      of headache per month). Headaches with a recent onset and judged unusual or
      worrisome by the patient (even one with frequent headaches) must raise the
      suspicion of a secondary cause and need to be investigated. Headaches that
      continue for months or years are more often primary, but secondary causes need to
      be ruled out in certain cases.

PMID- 20816420
TI  - Therapeutic guidelines for headache.

PMID- 20816421
TI  - The role of prevention.
AB  - Daily migraine medication prevention is indicated when migraine frequency and
      disability are high. Drug selection is predicated on comorbidity in order to
      treat multiple disorders at the same time, and using the highest level of
      evidence possible. Treatment is initiated at a low dose, working up to an
      effective dose, and maintained for at least 2-3 months, with headache diary
      monitoring for outcome. Poor outcome is associated with picking the wrong drug,
      an excessive initial dose, an inadequate final dose, too short a duration of
      treatment, or unrealistic expectations. The best evidence for preventive
      medications exists for amitriptyline, propranolol, timolol, valproate, and
      topiramate.

PMID- 20816422
TI  - Managing migraine associated with sensitization.
AB  - The majority of migraineurs seeking secondary or tertiary medical care experience
      throbbing pain and cutaneous allodynia during the course of migraine. Underlying
      the origin of these symptoms are peripheral and central trigeminovascular
      neurons, whose cell bodies are located in the trigeminal ganglion and the spinal
      dorsal horn, respectively. The development of throbbing in the initial phase of
      migraine is mediated by sensitization of peripheral trigeminovascular neurons,
      whereas the development of cutaneous allodynia later in the attack is propelled
      by sensitization of central trigeminovascular neurons which, unfortunately, are
      not equipped to respond to triptans directly. Triptans appear to act
      presynaptically in the dorsal horn, such as to inhibit signal transmission from
      peripheral to central trigeminovascular neurons. Reining in the central neurons
      using triptan treatment is possible as long as their excitability remains driven
      by incoming signals from the meninges, but not after they develop autonomous
      activity. Accordingly, attacks with allodynia can be effectively terminated,
      provided that the patient vigilantly resorts to triptan therapy before or soon
      after the onset of allodynia, but not after allodynia has become firmly
      established. On the other hand, allodynic patients who missed the critical window
      for effective triptan therapy can still be rendered pain-free using an
      intravenous infusion of non-steroidal anti-inflammatory drugs.

PMID- 20816423
TI  - Botulinum neurotoxin in the treatment of headache disorders.
AB  - Botulinum neurotoxin (BoNT) has been in clinical use for the treatment of
      headaches for over 15 years. Recent double-blind placebo-controlled trials have
      confirmed the efficacy of BoNT type A (onabtoulinumtoxinA, Botox) in the
      treatment of chronic migraine. The efficacy of BoNT in the treatment of episodic
      migraine headaches, cluster headaches, and chronic tension-type headache (TTH)
      has not been examined in large controlled trials. Presumed mechanisms of action
      of BoNT in headache disorders are the reduction of afferent input induced by
      muscle relaxation and inhibition of the release of neurotransmitters, such as
      glutamate and calcitonin gene-related peptide, from peripheral sensory nerve
      terminals. Over 20 years of extensive clinical experience has established a
      remarkable safety for BoNT, particularly type A and specifically Botox or
      onabotulinumtoxinA, which has been used much longer and more widely than any
      other form or serotype of BoNT. Because BoNT is a biological product, the safety
      and efficacy of one BoNT formulation cannot be extrapolated to a different one,
      even of the same serotype.

PMID- 20816424
TI  - The approach to the difficult patient.
AB  - Specific patient and physician characteristics may contribute to a perception
      that a particular headache patient is "difficult." Headache patients with
      psychiatric pathology, multiple unexplained symptoms, substance abuse problems,
      or refractory headaches are commonly perceived as challenging to manage.
      Physicians who are younger, under more stress, and who do not use collaborative
      treatment models are more likely to find patients difficult. General principles
      that may be helpful in coping with headache patients perceived as difficult
      include: (1) evaluation for possible psychiatric or substance abuse problems with
      institution of specific treatment if found; (2) a shift in treatment philosophy
      away from a goal of cure toward a goal of management; (3) the use of written
      agreements that outline conditions of treatment, including medication amounts;
      and (4) an integrated, multimodality treatment approach including behavioral and
      non-pharmacological treatment.

PMID- 20816425
TI  - Ethical issues in headache management.

PMID- 20816426
TI  - The role of lay associations.

PMID- 20816427
TI  - Migraine general aspects.

PMID- 20816428
TI  - Pathophysiology of migraine.

PMID- 20816429
TI  - Migraine--clinical neurophysiology.
AB  - Central nervous system (CNS) dysfunction is thought to be pivotal in migraine,
      and could occur at several levels: the brain (the cortex and its connections with
      subcortical nuclei), the brainstem, and even peripheral structures (e.g.,
      trigeminal ganglion and nerve). As it is particularly suited to functional
      evaluation of various components of the nervous system, neurophysiological
      testing has become a valuable tool for investigating migraine pathophysiology and
      the effects of pharmacological treatment. However it has limited value for
      migraine diagnosis because of a high interindividual variability. In this
      chapter, we critically review and summarize the available published literature on
      neurophysiological approaches in migraine, i.e., electroencephalography, evoked
      and event-related potentials, transcranial magnetic stimulation (TMS),
      electromyography, and cerebellar testing. The most relevant techniques for
      understanding migraine pathophysiological mechanisms are highlighted.

PMID- 20816430
TI  - Migraine clinical diagnostic criteria.

PMID- 20816431
TI  - Migraine and reproductive life.
AB  - Migraine is prevalent in women during the fertile age. Indeed, both
      neuroendocrine events related to reproductive stages (menarche, pregnancy, and
      menopause) and menstrual cyclicity and the use of exogenous sex hormones, such as
      hormonal contraception and replacement therapy, may cause significant changes in
      the clinical pattern of migraine. Menstrual migraine may be more severe, long
      lasting, and refractory to both acute and prophylactic treatment and, therefore,
      requires tailored strategies. The use of headache diaries, which makes it
      possible to record prospectively the characteristics of every attack, is of
      paramount importance for evaluating the time pattern of headache and for
      identifying a clear link with menstrual cycle-related features. Estrogen
      variations are highly implicated in modulating the threshold to challenges by
      altering neuronal excitability, cerebral vasoactivity, pain sensitivity, and
      neuroendocrine axes throughout the menstrual cycle and not only at the time of
      menstruation. On the other hand, estrogen withdrawal may really constitute a
      triggering factor for migraine in women with peculiar characteristics of
      vulnerability with menstruation or following the discontinuation of exogenous
      estrogen, as happens with hormonal contraception during the fertile age or with
      hormone therapy at menopause. In addition, exogenous estrogen may contribute to
      the occurrence of neurological symptoms, such as aura. When aura occurs, hormonal
      treatment should be discontinued.

PMID- 20816432
TI  - Acute treatment of migraine.
AB  - Acute treatment of migraine has benefited first from major advances in
      pharmacological science followed in short order, sometimes preceded, by an
      improved understanding of pathogenesis, especially of headache. This chapter
      reviews the mechanisms of migraine that provide an understanding of the
      pharmacology and therapeutic targets for acute migraine medications. General
      clinical approaches to acute therapy are reviewed, and indices of acceptable
      acute therapeutic outcomes are discussed. Currently the serotonin (5-HT) 1B/1D
      agonist group of drugs, triptans, forms the mainstay of acute therapeutic
      regimens. Other approaches to acute treatment such as simple analgesics, non
      steroidal anti-inflammatory drugs (NSAIDs), ergots, and combination medications
      are reviewed. Finally, the newest acute treatments that are currently exploratory
      or under clinical investigation are discussed.

PMID- 20816433
TI  - Migraine preventive treatment.
AB  - Migraine is a chronic neurological disease. Preventive therapy is given in an
      attempt to reduce the frequency, duration, or severity of attacks. Circumstances
      that might warrant preventive treatment include recurring migraine attacks that
      significantly interfere with the patient's daily routines, despite appropriate
      acute treatment; frequent headaches; contraindication to, failure of, overuse of,
      or intolerance to acute therapies; patient preference; frequent, very long, or
      uncomfortable auras; and presence of uncommon migraine conditions. The major
      medication groups for preventive migraine treatment include beta-adrenergic
      blockers, antidepressants, calcium channel antagonists, serotonin antagonists,
      and anticonvulsants. The choice of preventive treatment depends on the individual
      drug's efficacy and adverse events, the patient's clinical features, frequency,
      and response to prior treatment, and the presence of any comorbid or coexistent
      disease.

PMID- 20816434
TI  - Tension-type headache introduction and diagnostic criteria.
AB  - Tension-type headache is the most common primary headache syndrome. Lifetime
      prevalence ranges from 35% to 80%. There is a distinction between an episodic and
      a chronic form. This distinction is important, because the chronic subtype
      strongly implies a neurobiological basis and causes both impairment of quality of
      life and a high disability score, and is comorbid with anxiety and depressive
      disorders. The episodic tension-type headache is divided into an infrequent and a
      frequent subtype. It is known that the frequent type will often be transformed
      into the chronic type. Tension-type headache often coexists with migraine without
      aura; therefore both types of headache must be diagnosed separately. Additionally
      medication overuse headache has to be taken into account when diagnosing tension
      type headache. The following chapter reflects the diagnostic criteria for tension
      type headache in the context of the revised International Classification of
      Headache Disorder of the International Headache Society.

PMID- 20816435
TI  - Tension-type headache: mechanisms.

PMID- 20816436
TI  - The clinical neurophysiology of tension-type headache.
AB  - Despite being widely investigated, the pathogenesis of tension-type headache
      (TTH) continues to be debated. Among the different approaches used to explore the
      mechanisms underlying TTH, clinical neurophysiology plays an important role.
      Studies to date have focused mainly on two areas: (1) evaluation of peripheral
      factors (i.e., by electromyography (EMG)); and (2) exploration of the role of the
      pain control system. In the second of these areas, a large number of studies have
      explored trigeminal pathways, in particular using reflexes (e.g., the
      trigeminofacial reflex, trigeminotrigeminal reflexes). More recently, the
      descending inhibitory system, known to modulate both the trigeminal and the
      spinal system, has also been investigated. In addition, several studies have
      sought to establish whether there are neurophysiological parameters that could be
      markers of this condition, but the results of these were inconclusive, since some
      abnormalities could frequently be observed in migraine too. This chapter
      critically reviews the clinical neurophysiology of TTH. It concludes that the
      majority of neurophysiological studies on TTH present serious methodological
      flaws that will have to be overcome to allow further understanding of the
      mechanisms of TTH.

PMID- 20816437
TI  - Treatment of tension-type headache.

PMID- 20816438
TI  - Cluster headache and trigeminal autonomic cephalalgias general aspects.

PMID- 20816439
TI  - Pathophysiology of cluster headache and other trigeminal autonomic cephalalgias.

PMID- 20816440
TI  - Neuroimaging and clinical neurophysiology in cluster headache and trigeminal
      autonomic cephalalgias.
AB  - Clinical neurophysiology and neuroimaging are two non-invasive approaches used to
      investigate the pathophysiological basis of primary headaches, including cluster
      headache (CH) and other trigeminal autonomic cephalalgias (TACs). Modern
      neuroimaging has revolutionized our understanding of the pathophysiology of
      primary headaches, and of TACs in particular, focusing on a cerebrovascular
      dysfunction hypothesis toward a central triggering cause. The introduction of
      single-photon emission computed tomography (SPECT), positron emission tomography
      (PET), and voxel-based morphometry has allowed us new insights into mechanisms
      underlying TACs and occurring during peripheral and/or central neuromodulation.
      The specific activation of neural structures that is observed exclusively in
      migraine and in TACs supports the hypothesis that primary headaches are driven
      predominantly by central nervous system dysfunction, and this has important
      implications from a therapeutic perspective. Neurophysiological examinations are
      of little value in the clinical setting; however, most of these tools offer vast
      potential for exploring further the pathophysiology of primary headaches and the
      effects of pharmacological treatments Trigeminofacial reflexes, the nociceptive
      flexion reflex, and evoked potentials have been used in TACs to explore the
      functional state of brainstem and spinal structures involved in pain processing,
      contributing to our understanding of the pathophysiology of these primary
      headaches.

PMID- 20816441
TI  - Cluster headache and other trigeminal autonomic cephalalgias diagnostic criteria.

PMID- 20816442
TI  - Acute and preventive treatment of cluster headache and other trigeminal autonomic
      cephalgias.
AB  - Patients with cluster headache or any of the trigeminal autonomic cephalalgias
      (TACs) are often good candidates for preventive treatment as their headaches are
      frequent and severe. While acute and symptomatic therapies must be used often,
      they do not alter the course of the cluster period or the duration of the TACs,
      and they do not usually decrease the frequency of attacks. In this chapter we
      discuss the aim and the choice of prevention. Verapamil is considered the first
      choice for prevention of cluster headache, but as with all of the medications to
      be mentioned, it has various adverse effects to be aware of. Other frequently
      used preventives for cluster include lithium carbonate, methysergide where
      available, methylergonovine, clonidine, melatonin, valproate, gabapentin,
      topiramate, and others. Several other medications can be used as bridge therapy,
      to decrease the frequency of cluster temporarily, giving time for the preventives
      to begin to work. The most commonly used bridge therapies are 7-21 days of
      prednisone at high and then tapering doses and ergots such as ergotamine tartrate
      and dihydroergotamine. Patients with chronic cluster headache who are
      unresponsive to all medical therapies can be considered for occipital nerve
      stimulation and various surgical procedures such as ganglyogliolysis of all three
      branches of the ipsilateral trigeminal nerve at the root entry zone. A somewhat
      controversial but highly successful procedure, at least as done by the
      neurosurgeons in Professor Bussone's group at the Institute of Neurology in
      Milan, has been deep-brain stimulation of the posterior hypothalamus. Other TACs,
      such as short-lasting unilateral neuralgiform headache attacks with conjunctival
      injection and tearing (SUNCT), can be hard to treat effectively with medications,
      but the paroxysmal hemicranias and cluster tic respond somewhat better to
      traditional therapies.

PMID- 20816443
TI  - Neurostimulation therapy in intractable headaches.
AB  - A proportion of chronic headache patients become refractory to medical treatment
      and severely disabled. In such patients various neurostimulation methods have
      been proposed, ranging from invasive procedures such as deep-brain stimulation to
      minimally invasive ones like occipital nerve stimulation. They have been applied
      in single cases or small series of patients affected with varying headache
      disorders: cervicogenic headache, hemicrania continua, posttraumatic headache,
      chronic migraine, and cluster headache. Although favorable results were reported
      overall, it is premature to consider neurostimulation as a treatment with
      established utility in refractory headaches. At present, the most detailed
      clinical studies have been performed in intractable chronic cluster headache
      (iCCH) patients, who represent about 1% of all chronic cluster headache (CCH)
      patients. Various lesional interventions have been attempted in these patients,
      none with lasting benefits. In recent years, non-destructive neurostimulation
      methods have raised new hope. Hypothalamic deep-brain stimulation (hDBS) acts
      rapidly and has lasting efficacy, but is not without risk. Occipital nerve
      stimulation (ONS) was studied in two trials on a total of 17 iCCH patients.
      Clinical efficacy was found to be very satisfactory by most patients and by the
      investigators. Although slightly less efficacious than hDBS, ONS has the
      advantage of being rather harmless and reversible. At this stage, it should be
      preferred as first-line invasive therapy for iCCH. Recent case reports mention
      the efficacy of supraorbital (SNS) and vagal (VNS) nerve stimulation. Whether
      these neurostimulation methods have a place in the management of iCCH patients
      remains to be determined.

PMID- 20816444
TI  - Other primary headaches--general aspects.

PMID- 20816445
TI  - Primary stabbing headache.
AB  - Primary stabbing headache is characterized by transient, cephalic ultrashort
      stabs of pain. It is a frequent complaint with a prevalence of 35.2%, a female
      preponderance, and a mean age of onset of 28 years (Vaga study). Attacks are
      generally characterized by moderate to severe, jabbing or stabbing pain, lasting
      from a fraction of a second to 3s. Attack frequency is generally low, with one or
      a few attacks per day. The paroxysms generally occur spontaneously, during
      daytime. Most patients exhibit a sporadic pattern, with an erratic, unpredictable
      alternation between symptomatic and non-symptomatic periods. Paroxysms are almost
      invariably unilateral. Temporal and fronto-ocular areas are most frequently
      affected. Attacks tend to move from one area to another, in either the same or
      the opposite hemicranium. Jabs may be accompanied by a shock-like feeling and
      even by head movement - "jolts" -or vocalization. On rare occasions, conjunctival
      hemorrhage and monocular vision loss have been described as associated features.
      Primary stabbing headache may concur, synchronously or independently, with other
      primary headaches. In contrast to what is the case in adults, in childhood it is
      not usually associated with other headaches. Treatment is rarely necessary.
      Indomethacin, 75-150 mg daily, may seem to be of some avail. Celecoxib,
      nifedipine, melatonin, and gabapentin have been reported to be effective in
      isolated cases and small series of patients. The drug studies need corroboration.

PMID- 20816446
TI  - Primary cough headache, primary exertional headache, and primary headache
      associated with sexual activity.
AB  - Activity-related headaches can be brought on by Valsalva maneuvers ("cough
      headache"), prolonged exercise ("exertional headache"), and sexual excitation
      ("orgasmic headache"). These headaches account for 1-2% of the consultations due
      to headache in a general neurological department. These entities are a
      challenging diagnostic problem as they can be primary or secondary and as their
      etiologies differ depending on the headache type. About 50% of patients with
      cough headache will show no demonstrable etiology, while the other half will be
      secondary to structural lesions, mostly a Chiari type I malformation at the
      foramen magnum level. As compared to the primary variety, secondary cough
      headache begins earlier (average 40 versus 60 years), is located posteriorly,
      lasts longer (years versus months), is associated with posterior fossa
      symptoms/signs, and does not respond to indomethacin. Patients with secondary
      cough headache show difficulties in cerebrospinal fluid circulation in the
      foramen magnum region in dynamic magnetic resonance imaging studies and
      preoperative plateau waves, which disappear after posterior fossa reconstruction.
      Headaches provoked by physical exercise and sexual headache have many points in
      common. In contrast to cough headache, secondary cases are rare, and sentinel
      subarachnoid bleeding is the most frequent etiology. The mean age at onset for
      primary headaches provoked by physical exercise and sexual activity is similar
      (40 years); they share clinical characteristics (bilateral, pulsating) and
      respond to beta-blockers. In conclusion, provoked headaches account for a low
      proportion of headache consultations. Cough headache is a different condition
      when compared to headache due to physical exercise and sexual activity, which are
      clinical variants of the same entity.

PMID- 20816447
TI  - Hypnic headache.
AB  - Hypnic headache (HH), originally described by Raskin in 1988 as a late-onset,
      "curious sleep-related headache syndrome," has also been called "alarm-clock
      headache" as it regularly awakens subjects from sleep at a set time of night. In
      general, onset of HH is late in life with a chronic course. The most important
      characteristics of HH are: occurrence exclusively during sleep, chronic pattern
      of attacks (>/=15 per month), short duration, dull pain, and absence of autonomic
      signs and symptoms. The criteria adopted by the Second Edition of the
      International Classification of Headache Disorders (ICHD-II, Headache
      Classification Subcommittee of the International Headache Society, 2004) do not
      take into account the location, duration, and intensity of the pain. This is
      probably because the pain features and patterns are quite variable. In most cases
      HH is a primary headache form, but, because it begins late in life, it is
      mandatory to exclude an underlying disorder. In particular, nocturnal headaches
      secondary to increased intracranial pressure, arterial hypertension, sleep apnea,
      or pain-killing medication overuse must be ruled out. The co-occurrence of other
      types of primary headache in the same period or in different periods of life has
      been reported in about 40% of HH patients.

PMID- 20816448
TI  - Primary thunderclap headache.
AB  - Thunderclap headache is an uncommon type of headache, but recognition and
      diagnosis are important because of the possibility of a serious underlying brain
      disorder. In this chapter, primary thunderclap headache in relation to other
      primary headache disorders and secondary, symptomatic headache disorders are
      discussed. Most importantly, subarachnoid hemorrhage should be excluded. The
      first investigation is a computed tomography (CT) scan, and, if the CT scan is
      negative, investigation of the cerebrospinal fluid. Other symptomatic vascular
      causes are intracranial hemorrhage, cerebral venous sinus thrombosis, cervical
      artery dissection, or a reversible vasoconstriction syndrome. These and other
      serious underlying intracranial disorders should be detected by magnetic
      resonance imaging or the appropriate investigations. The remaining patients with
      thunderclap headache most likely represent a primary headache disorder, including
      migraine, primary cough headache, primary exertional headache, or primary
      headache associated with sexual activity. Within the group of primary headache
      disorders, primary thunderclap headache represents a distinct clinical entity; it
      is characterized by a sudden severe headache lasting from 1h up to 10 days and
      not attributed to another disorder. The pathogenesis of primary thunderclap
      headache is still not known, but the sympathetic nervous system may play an
      important role.

PMID- 20816449
TI  - Hemicrania continua.

PMID- 20816450
TI  - New daily persistent headache.
AB  - New daily persistent headache (NDPH) is a unique form of chronic daily headache
      (CDH) which is marked by a daily headache from onset, typically occurring in
      individuals without a significant prior history of headaches. There are two
      subforms of NDPH: one which is self-limited and normally goes away without
      therapy, and a more chronic refractory form which is unresponsive to typical
      headache treatment strategies. The pathogenesis of NDPH is unknown but recent
      observations suggest a connection with cervical spine hypermobility and elevation
      of proinflammatory cytokines in the cerebrospinal fluid (CSF). Recognized
      triggers for NDPH include infection, stressful life events, and surgical
      procedures. Clinically, NDPH is characterized by continuous head pain of mild to
      severe intensity. Migrainous symptoms are common. The syndrome appears to affect
      women in their teens and 20s, while males develop NDPH later in life in their 50s
      or 60s. There are no recognized treatments for this condition, although treatment
      options will be discussed. Secondary mimics of NDPH will also be touched upon in
      this chapter.

PMID- 20816451
TI  - Secondary headaches introduction.

PMID- 20816452
TI  - Headache attributed to head or neck trauma.

PMID- 20816453
TI  - Headache attributed to stroke, TIA, intracerebral haemorrhage, or vascular
      malformation.
AB  - Headache is relatively common in patients with cerebrovascular disorders. The
      reported frequency of stroke-related headache ranges from 7% to 65% and different
      types of headache, such as onset headache, sentinel headache, or delayed
      headache, may be observed in association with stroke. Headache can be attributed
      to ischemic stroke, transient ischemic attack, or non-traumatic intracranial
      hemorrhage, including intracerebral and subarachnoid hemorrhage. Headache at
      stroke onset is more common in subarachnoid hemorrhage, most prominently
      associated with severe headache, and in intracerebral hemorrhage than in ischemic
      stroke or transient ischemic attack. The typical presentation of subarachnoid
      hemorrhage includes the sudden onset of severe headache with nausea, vomiting,
      neck pain, photophobia, and loss of consciousness. Headache is the only symptom
      in about a third of patients with subarachnoid hemorrhage. The suddenness of
      onset and not its severity is the characteristic feature of the headache in
      subarachnoid hemorrhage. Referring to unruptured vascular malformations, the
      headache can be attributed to saccular aneurysm, arteriovenous malformation,
      dural arteriovenous fistula, dural cavernous angioma, and encephalotrigeminal or
      leptomeningeal angiomatosis (Sturge-Weber syndrome). It is very important to
      recognize that in the latter forms the onset of headache may indicate an upcoming
      bleeding complication.

PMID- 20816454
TI  - Headache attributed to arteritis, cerebral venous thrombosis, and other vascular
      intracranial disturbances.
AB  - Headache with variable characteristics and associated signs and symptoms may
      occur in all forms of arteritis. Giant cell arteritis, one of the most common
      forms, involves branches of the external and, more rarely, of the internal
      carotid arteries. It occurs in patients over the age of 50 and is characterized
      by fever, new-onset headache, prominence and tenderness of the temporal artery,
      claudication of the masticatory muscles on chewing, amaurosis fugax, and visual
      loss. Headache is the initial symptom in 48% of patients and is present in 90%.
      Primary central nervous system angiitis is a rare and highly fatal disease in
      which headache is one of the most frequent symptoms despite the fact that, given
      its non-specific characteristics, it is of little diagnostic relevance. Headache
      may also be attributed to several secondary central nervous system arteritides
      such as Behcet's disease, Takayasu disease, polyarteritis nodosa, Kawasaki
      disease, Wegener's granulomatosis, systemic lupus erythematosus, and vasculitits
      caused by viruses, bacteria, fungi, rickettsiae, and protozoa. Thrombosis of the
      cerebral veins and sinuses is a distinct cerebrovascular disorder that, unlike
      arterial stroke, most often affects young adults and children. Headache is the
      most frequent but least specific symptom of venous sinus thrombosis, being
      present in more than 90% of patients. Headache can also be attributed to other
      vascular intracranial disorders such as cerebral autosomal-dominant arteriopathy
      with subcortical infarcts and leukoencephalopathy (CADASIL), mitochondrial
      encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), benign (or
      reversible) angiopathy of the central nervous system, and pituitary apoplexy.

PMID- 20816455
TI  - Headache attributed to carotid or vertebral artery pain.
AB  - Headache or pain in the face or neck attributed to the carotid or vertebral
      artery was not recognized as a special type of pain until the concept of
      carotidynia occurred in the 1960s. Carotidynia has long been assumed as an entity
      until modern imaging techniques showed that pain localized in the carotid region
      could most often be related to injury of the artery or other symptomatic causes.
      These causes include headache due to arterial dissection, which has been
      described as a true pain originating from the vessel structure itself and which
      has also been attributed to a comorbidity of migraine and cervical artery
      dissection. Furthermore, headache starting after endarterectomy, carotid
      angioplasty headache, headache attributed to intracranial endovascular
      procedures, and angiography headache have been listed among the headache and pain
      syndromes due to changes of the cervical arteries. It is still not clarified
      whether carotidynia is a specific idiopathic disease or whether the previous
      descriptions of carotidynia just resembled symptomatic causes of carotid pain.

PMID- 20816456
TI  - Headache attributed to non-vascular intracranial disorder.
AB  - This chapter deals with non-vascular intracranial disorders resulting in
      headache. Headache attributed to high or low cerebrospinal fluid pressure is
      separated into headache attributed to idiopathic intracranial hypertension (IIH),
      headache attributed to intracranial hypertension secondary to metabolic, toxic,
      or hormonal causes, headache attributed to intracranial hypertension secondary to
      hydrocephalus, post-dural puncture headache, cerebrospinal fluid (CSF) fistula
      headache, headache attributed to spontaneous (or idiopathic) low CSF pressure.
      Headache attributed to non-infectious inflammatory disease can be caused by
      neurosarcoidosis, aseptic (non-infectious) meningitis or lymphocytic
      hypophysitis. Headache attributed to intracranial neoplasm can be caused by
      increased intracranial pressure or hydrocephalus caused by neoplasm or attributed
      directly to neoplasm or carcinomatous meningitis. Other causes of headache
      include hypothalamic or pituitary hyper- or hyposecretion and intrathecal
      injection. Headache attributed to epileptic seizure is separated into hemicrania
      epileptica and post-seizure headache. Finally headache attributed to Chiari
      malformation type I (CM1) and the syndrome of transient headache and neurological
      deficits with cerebrospinal fluid lymphocytosis (HaNDL) are described.

PMID- 20816457
TI  - Headache attributed to a substance or its withdrawal.
AB  - Medication overuse, and subsequent medication overuse headache (MOH), is a
      growing and still underestimated problem worldwide. A significant number of
      recent epidemiological studies suggest that up to 4% of the general population in
      Europe, North America, and Asia overuse analgesics and other drugs for the
      treatment of pain conditions such as migraine. These studies also provide
      convincing evidence that about 1% of the general population suffers from MOH. The
      condition can be caused by almost all antiheadache drugs, including analgesics,
      ergots, triptans, and combined preparations. The clinical symptoms of MOH are
      heterogeneous and may vary from just an increase in headache attack frequency to
      a constant holocranial pain over years. The International Headache Society (IHS)
      defined MOH in its first classification in 1988 but modified the diagnostic
      criteria in its second classification in 2004 to facilitate diagnosis and the
      conduct of clinical trials. The underlying pathophysiology of MOH is not well
      understood. The only therapy is withdrawal from the overused substances. The only
      strategy to reduce the prevalence of MOH is to prevent the development of MOH in
      the first place by clear restriction of monthly doses of antiheadache drugs and
      constant education of both patients and physicians prescribing or recommending
      antiheadache drugs.

PMID- 20816458
TI  - Headache attributed to infections nosography and differential diagnosis.
AB  - Headache is a very frequent symptom of infection. It has many possible underlying
      mechanisms, of which two or more can coexist in a single patient. It can be
      caused by direct stimulation of intracranial pain-producing structures, as in the
      case of brain abscesses, by irritation of the pachy- and leptomeninges, as in
      cases of bacterial or viral meningitis, or by a state of intracranial
      hypertension, as seen in obstructive hydrocephalus. There is no doubt that
      headache is often the first or the predominant symptom of serious, sometimes life
      threatening, infectious diseases; certainly, it is a condition frequently
      encountered in all epidemiological studies. Indeed, it is estimated that over 60%
      of people have, at some point in their lives, experienced headache during an
      infection. This evidence leads to the need for a systematic approach to headache
      secondary to infection. This chapter provides some elements on pain mechanisms in
      systemic and intracranial infections and on the possible role of antimicrobial
      agents in the genesis of headache. The first section provides a detailed
      "etiology-based" description of the International Classification of Headache
      Disorders, 2nd edition (ICHD-II: Headache Classification Subcommittee of the
      International Headache Society, 2004), while the second section presents a
      "symptom-based" algorithm applicable in the first diagnostic assessment,
      according to the headache features and to the most frequently associated clinical
      manifestations during infections of the central nervous system (CNS).

PMID- 20816459
TI  - Headache attributed to disorders of homeostasis.

PMID- 20816460
TI  - Headache or facial pain attributed to disorders of cranium, neck, eyes, ears,
      nose, sinuses, teeth, mouth, or other facial or cranial structures.

PMID- 20816461
TI  - Headache attributed to psychiatric disorders.
AB  - The association between psychiatric illness and headache is widely recognized.
      "Headache attributed to psychiatric disorder" is a new category of secondary
      headache introduced in the 2004 revision of the International Classification of
      Headache Disorders (ICHD-II) (Headache Classification Subcommittee of the
      International Headache Society, 2004). It represents a new, but not conclusive,
      step toward a better systematization of the topic "headache and psychological
      factors." From the early 1990s the involvement of psychological factors in
      headache disorders has been clearly identified as "psychiatric comorbidity." The
      current conceptualization of the term implies an association, more than casual,
      but likely not causal, between an index disease or disorder and one or more
      coexisting physical or psychological pathologies. Additionally, clarifying the
      direction, meaning, and weight of comorbidities has pathophysiological,
      nosological, course, and treatment implications. However, the study of
      comorbidity may present a series of difficulties related to the current
      understanding of the etiology and pathophysiology of diseases at the center of
      our attention. Sometimes, as happens in the subject of headache, we proceed
      against a background where many issues need to be clarified. In this chapter, we
      analyze the past and current literature, tracing the line from "migraine
      personality" to "psychiatric comorbidity" to "headache attributed to psychiatric
      disorders." Questions related to etiology, pathophysiology, and treatment options
      are discussed for different headache subtypes.

PMID- 20816462
TI  - Cranial neuralgias.
AB  - After a description of the anatomical-functional organization of the human
      trigeminal system, this chapter discusses the diagnostic and therapeutic options
      for trigeminal neuralgia (TN). In about 15% of patients who present with the
      clinical picture of typical TN, this is secondary to a major neurological
      disease, i.e., benign tumors of the cerebellopontine angle or multiple sclerosis.
      Some clinical criteria that were used to distinguish between classic and
      symptomatic TN, such as age at onset, involvement of the ophthalmic division, and
      responsiveness to medical treatment, are no longer considered reliable. It is
      recommended that all patients undergo magnetic resonance imaging (MRI) or
      trigeminal reflex recording. Carbamazepine (CBZ) and oxcarbazepine (OXC) are the
      first-choice medical treatments. Although other drugs may be effective, these are
      indicated when the patient cannot reach the therapeutic dosage of CBZ/OXC because
      of adverse events. Patients unresponsive to CBZ/OXC should be made aware of the
      available surgical interventions. Surgical procedures (including percutaneous
      lesions to the ganglion/root, microvascular decompression (MVD) in the posterior
      fossa, and gamma knife radiosurgery) are extremely efficacious with relatively
      few complications: each procedure has some advantage and disadvantage with
      respect to the other. Only MVD is a non-destructive procedure. This chapter also
      describes management of glossopharyngeal neuralgia, which is often misdiagnosed,
      and some other chronic pain conditions mediated by the trigeminal system, such as
      ophthalmic postherpetic neuralgia (PHN).

PMID- 20816463
TI  - Surgical treatment of cranial neuralgias.
AB  - The most common types of cranial neuralgias amenable to surgical therapeutic
      options are trigeminal neuralgia and glossopharyngeal neuralgia, the former
      having an approximate incidence of 5/100000 cases per year and the latter of
      0.05/100000 cases per year. Surgical therapy of these pathological conditions
      encompasses several strategies, going from ablative procedures to neurovascular
      decompression, to radiosurgery. The choice of the most appropriate surgical
      option (which must be taken into account when all conservative treatments have
      proven to be unsuccessful) has to take into account many factors, the most
      important ones being neuroradiological evidence of a neurovascular conflict,
      severity of symptoms, the age and clinical history of the patient, and the
      patient's overall medical condition. In this chapter we report our experience
      with the treatment of trigeminal and glossopharyngeal neuralgia, describing the
      surgical procedures performed and reviewing the most recent aspects on this
      subject in the past literature.

PMID- 20816464
TI  - Central pain in the face and head.
AB  - All kinds of lesions in the central nervous system can induce central neuropathic
      pain (e.g., stroke, multiple sclerosis, spinal cord injury, syringobulbia,
      syringomyelia). The location is the most important feature of the lesion. In
      stroke, the onset of pain is often delayed. It is mostly constant, but it may be
      intermittent or paroxysmal. In stroke patients the pain is frequently a hemipain
      (75%), whereas in the 28% of all multiple sclerosis patients who develop central
      pain it dominates in the legs (87%) and 5% have trigeminal neuralgia caused by
      lesions in the brainstem. There is a large variation in the quality of central
      pain. Central pain is associated with abnormalities in sensitivity to temperature
      and pain. It is hypothesized that central pain is caused by lesions of the
      spinothalamic pathways, including their thalamocortical projections, but some
      other (unknown) factors appear to be crucial for the development of the pain
      because many patients with such lesions do not develop central pain. Central pain
      usually responds poorly to analgesics. The first-line treatments are tricyclic
      antidepressants and antiepileptic drugs.

PMID- 20816465
TI  - Chronobiological correlates of primary headaches.

PMID- 20816466
TI  - Headache endocrinological aspects.
AB  - In this chapter we review the current understanding of how hormones,
      neurohormones, and neurotransmitters participate in the pain modulation of
      primary headaches. Stressful conditions and hormones intimately implicated in
      headache neurobiology are also discussed. With the recent progress in
      neuroimaging techniques and the development of animal models to study headache
      mechanisms, the physiopathology of several of the primary headaches is starting
      to be better understood. Various clinical characteristics of the primary
      headaches, such as pain, autonomic disturbances, and behavioral changes, are
      linked to hypothalamic brainstem activation and hormonal influence. Headache is
      greatly influenced by the circadian circle. Over the millennia the nervous system
      has evolved to meet changing environmental conditions, including the light-dark
      cycle, in order to ensure survival and reproduction. The main elements for
      synchronization between internal biological events and the external environment
      are the pineal gland and its main secretory product, melatonin. Melatonin is
      believed to be a significant element in migraine and in other headache disorders,
      which has implications for treatment. A potential therapeutic use of melatonin
      has been considered in several headache syndromes. In short, primary headaches
      are strongly influenced by physiological hormonal fluctuations, when nociceptive
      and non-nociceptive pathways are differentially activated to modulate the
      perception of pain.

PMID- 20816467
TI  - Headache in children.
AB  - Headache is an extremely frequent symptom in childhood and adolescence, and a
      common reason for neurological consultation. The prevalence of primary headaches
      (about 85% in tertiary centers) ranges from 10% to 20% in schoolchildren, and
      increases with increasing age. No sex difference is apparent until age 11. Female
      preponderance begins about age 12; during adolescence the female-to-male ratio is
      about 2:1. A child is not a "little adult" and many developmental and individual
      factors affect headaches, pertaining to the clinical expression, diagnosis, and
      therapy of the primary headache. According to this view, several points have to
      be clarified, beginning by considering the child as a whole as regards his or her
      development, taking into account neurobiological and psychological maturational
      processes, familial, social, and environmental factors, and avoiding an adult
      focused approach to the disease. It is necessary to find key points in the
      etiology, pathogenesis, diagnosis, treatment, and outcome of headache in
      childhood and adolescence.

PMID- 20816468
TI  - Vestibular migraine.
AB  - Vestibular migraine is a chameleon among the episodic vertigo syndromes because
      considerable variation characterizes its clinical manifestation. The attacks may
      last from seconds to days. About one-third of patients presents with
      monosymptomatic attacks of vertigo or dizziness without headache or other
      migrainous symptoms. During attacks most patients show spontaneous or positional
      nystagmus and in the attack-free interval minor ocular motor and vestibular
      deficits. Women are significantly more often affected than men. Symptoms may
      begin at any time in life, with the highest prevalence in young adults and
      between the ages of 60 and 70. Over the last 10 years vestibular migraine has
      evolved into a medical entity in dizziness units. It is the most common cause of
      spontaneous recurrent episodic vertigo and accounts for approximately 10% of
      patients with vertigo and dizziness. Its broad spectrum poses a diagnostic
      problem of how to rule out Meniere's disease or vestibular paroxysmia. Vestibular
      migraine should be included in the International Headache Classification of
      Headache Disorders (ICHD) as a subcategory of migraine. It should, however, be
      kept separate and distinct from basilar-type migraine and benign paroxysmal
      vertigo of childhood. We prefer the term "vestibular migraine" to "migrainous
      vertigo," because the latter may also refer to various vestibular and non
      vestibular symptoms. Antimigrainous medication to treat the single attack and to
      prevent recurring attacks appears to be effective, but the published evidence is
      weak. A randomized, double-blind, placebo-controlled study is required to
      evaluate medical treatment of this condition.

PMID- 20816469
TI  - Pharmacological migraine provocation: a human model of migraine.
AB  - In vitro studies have contributed to the characterization of receptors in cranial
      blood vessels and the identification of possible new antimigraine agents. Animal
      models enable the study of vascular responses, neurogenic inflammation, and
      peptide release, and thus have provided leads in the search for migraine
      mechanisms. So far, however, animal models cannot predict the efficacy of new
      therapies for migraine. Because migraine attacks are fully reversible and can be
      aborted by therapy, the headache- or migraine-provoking property of naturally
      occurring signaling molecules can be tested in a human model. If a naturally
      occurring substance can provoke migraine in human patients, then it is likely,
      although not certain, that blocking its effect will be effective in the treatment
      of acute migraine attacks. To this end, a human in vivo model of experimental
      headache and migraine in humans has been developed. This model has predicted the
      efficacy of nitric oxide synthase inhibition and calcitonin gene-related peptide
      receptor blockade, and has been used to examine other endogenous signaling
      molecules as well as genetic susceptibility factors.

PMID- 20816470
TI  - Neuroimaging in headache.
AB  - The neurobiology of migraine is complex, but considerable progress has been made
      during recent decades with the aid of functional neuroimaging. Imaging studies
      have provided evidence of both abnormal brain functioning and structural changes.
      In migraine aura, the blood flow changes initially occur in V3A, an area also
      showing morphometric abnormalities. Pontine activation is also associated with
      increased volumetric changes. Similar findings are observed in the hypothalamic
      region in cluster headache. Other paroxysmal headache disorders, such as short
      lasting unilateral neuralgiform headache attacks with conjunctival injection and
      tearing (SUNCT), hemicrania paroxistica and hemicrania continua, share this
      similar pattern of activation as cluster headache, pointing to a common
      pathogenic mechanism. Further studies are required in order to determine whether
      these changes are the cause or the consequence of the disease, as well as the
      possible role they may play in the progression into a chronic disorder.

PMID- 20816471
TI  - Current and emerging therapies for migraine prevention and treatment.

PMID- 20816473
TI  - Mass spectrometric analysis of sulfated N- and O-glycans.
AB  - Sulfated N- and O-glycans carried on a myriad of cell-surface adhesion molecules
      and receptors are often not detected by current approaches in mass spectrometry
      (MS)-based glycomic mapping of cells and tissues. This is in part due to a
      natural lower abundance, compounded further by their negatively charged nature,
      which adversely disfavors their ionization and detection amid a sea of often much
      more abundant, nonsulfated, sialylated glycans. However, this particular
      limitation can actually be taken advantage of to effect highly selective
      enrichment and sensitive MS screening in negative ion mode, provided the
      ubiquitous sialic acids can first be neutralized. It has been demonstrated that
      permethylation not only fulfills this role adequately but further confers better
      MS/MS fragmentation characteristics for more efficient structural mapping and
      sequencing. Protocols and general practical considerations are described here
      which would enable one to readily prepare permethylated sulfated glycans,
      fractionate them away from the more abundant nonsulfated ones in simple steps for
      high-sensitivity MS analysis, and sensibly interpret the initial sulfoglycomic
      screening data thus obtained.

PMID- 20816474
TI  - Mass spectrometric analysis of mutant mice.
AB  - Mass spectrometry (MS) has proven to be the preeminent tool for the rapid, high
      sensitivity analysis of the primary structure of glycans derived from diverse
      biological sources including cells, fluids, secretions, tissues, and organs.
      These analyses are anchored by matrix-assisted laser desorption ionization time
      of flight (MALDI-TOF) analysis of permethylated derivatives of glycan pools
      released from the samples, to produce glycomic mass fingerprints. The application
      of complimentary techniques, such as chemical and enzymatic digestions, GC-MS
      linkage analysis, and tandem mass spectrometry (MS/MS) utilizing both
      electrospray (ES) and MALDI-TOF/TOF, together with bioinformatic tools allows the
      elucidation of incrementally more detailed structural information from the
      sample(s) of interest. The mouse as a model organism offers many advantages in
      the study of human biology, health, and disease; it is a mammal, shares 99%
      genetic homology with humans and its genome supports targeted mutagenesis in
      specific genes to produce knockouts efficiently and precisely. Glycomic analyses
      of tissues and organs from mice genetically deficient in one or more
      glycosylation gene and comparison with data collected from wild-type samples
      enables the facile identification of changes and perturbations within the
      glycome. The Consortium for Functional Glycomics (CFG) has been applying such MS
      based glycomic analyses to a range of murine tissues from both wild-type and
      glycosylation-knockout mice in order to provide a repository of structural data
      for the glycobiology community. In this chapter, we describe in detail the
      methodologies used to prepare, derivatize, purify, and analyze glycan pools from
      mouse organs and tissues by MS. We also present a summary of data produced from
      the CFG systematic structural analysis of wild-type and knockout mouse tissues,
      together with a detailed example of a glycomic analysis of the Mgat4a knockout
      mouse.

PMID- 20816475
TI  - Glycosaminoglycan characterization by electrospray ionization mass spectrometry
      including fourier transform mass spectrometry.
AB  - Electrospray ionization mass spectrometry (ESI MS) is a versatile analytical
      technique in glycomics of glycosaminoglycans (GAGs). Combined with enzymology,
      ESI MS is used for assessing changes in disaccharide composition of GAGs
      biosynthesized under different environmental or physiological conditions. ESI
      coupled with high-resolution mass analyzers such as a Fourier transform mass
      spectrometer (FTMS) permits accurate mass measurement of large oligosaccharides
      and intact GAGs as well as structural characterization of GAG oligosaccharides
      using information-rich fragmentation methods such as electron detachment
      dissociation. The first part of this chapter describes methods for disaccharide
      compositional profiling using ESI MS and the second part is dedicated to FTMS and
      tandem MS methods of GAG compositional and structural analysis.

PMID- 20816476
TI  - Large-scale glycomics for discovering cancer-associated N-glycans by integrating
      glycoblotting and mass spectrometry.
AB  - It has known that the glycosylation plays an important role in the biological
      states, such as development, aging, and diseases. Although genomic and proteomic
      approaches have been intensively studied for diagnosis and disease treatment,
      glycomics have been laggard compared to them due to the hardness of the
      purification procedure from crude biological materials. Recently, we have
      developed "glycoblotting" method, a high-throughput and quantitative technique
      for comprehensive glycomics, which enables to enrich and quantify glycans from
      crude biological materials, such as serum, tissue biopsy, and cell lysate
      [Niikura, K., Kamitani, R., Kurogochi, M., Uematsu, R., Shinohara, Y., Nakagawa,
      H., Deguchi, K., Monde, K., Kondo, H., and Nishimuram S.-I. (2005). Versatile
      glycoblotting nanoparticles for high-throughput protein glycomics. Chem. Eur. J.
      11, 3825-3834; Nishimuara, S.-I., Niikura, K., Kurogochi, M., Matsushita, T.,
      Fumoto, M., Hinou, H., Kamitani, R., Nakagawa, H., Deguchi, K., Miura, N., Monde,
      K., and Kondo, H. (2005). High-throughput protein glycomics: Combined use of
      chemoselective glycoblotting and MALDI-TOF/TOF mass spectrometry. Angew. Chem.
      Int. Ed.44, 91-96]. The automated machine for glycoblotting, "SweetBlot," fixed
      to use optimized protocol allows us to obtain quantitative profile of 40-50 kinds
      of major glycoforms from 5mul of human serum within 11h. Based on the method, we
      have detected potential differences of N-glycome between sera from hepatocellular
      carcinoma (HCC) and healthy donor [Miura, Y., Hato, M., Shinohara, Y., Kuramoto,
      H., Furukawa, J.-i, Kurogochi, M., Shimaoka, H., Tada, M., Nakanishi, K., Ozaki,
      M., Todo, S., and Nishimura, S.-I. (2008). BlotGlycoABC(TM), an integrated
      glycoblotting technique for rapid and large scale clinical glycomics. Mol. Cell.
      Proteomics7, 370-377]. The method also permitted cellular quantitative N
      glycomics to monitor the process of dynamic cellular differentiation of mouse
      embryonic stem cells into neural cells [Amano, M., Yamaguchi, M., Takegawa, Y.,
      Yamashita, T., Terashima, M., Furukawa, J.-i., Miura, Y., Shinohara, Y., Iwasaki,
      N., Minami, A., and Nishimura, S.-I. (2010). Threshold in stage-specific
      embryonic glycotypes uncovered by a full portrait of dynamic N-glycan expression
      during cell differentiation. Mol. Cell. Proteomics9, 523-537]. In this chapter,
      we will discuss glycoblotting method including the potentials not only for
      exploration of glycan-related cancer biomarker but also for detection of cellular
      differentiation.

PMID- 20816477
TI  - In vitro and in vivo enzymatic syntheses and mass spectrometric database for N
      glycans and o-glycans.
AB  - In the GlycoGene Project, we have comprehensively cloned novel human genes
      associated with the synthesis of glycans using bioinformatics technology.
      Recombinant glycosyltransferases can be expressed in various expression systems.
      Diverse glycan structures are easily and rapidly achieved using these
      glycosyltransferases in vitro. Additionally, we have developed an in vivo
      production system for mammalian mucin-type glycopeptides using a genetically
      engineered yeast strain. This system enables the generation of glycopeptides
      which are O-glycosylated on a specific position by introducing different types of
      ppGalNAc-T genes. As an application of the glycan and glycopeptide libraries to
      glycan analysis, we have constructed a multistage tandem mass (MS(n)) spectral
      database containing observed MS(n) spectra. Using the MS(n) spectral database, it
      is possible to identify glycan structures very easily and rapidly by spectral
      matching.

PMID- 20816478
TI  - Identification of fucosylated haptoglobin as a novel tumor marker for pancreatic
      cancer and its possible application for a clinical diagnostic test.
AB  - Fucosylation is one of the most important oligosaccharide modifications in cancer
      and inflammation. The fucosylation level is increased in total cellular proteins
      of cancer cells as well as in sera of patients with cancer. Recently, on AAL blot
      analysis, we found a fucosylated glycoprotein of 40 kDa in sera of patients with
      pancreatic cancer. Based on its N-terminal sequence, this protein was identified
      as haptoglobin. Fucosylated haptoglobin was increased in sera of patients with
      several kinds of cancer and the positive rate was higher in pancreatic cancer.
      The level of fucosylated haptoglobin was not correlated with total haptoglobin,
      suggesting that a factor other than inflammation could regulate the production of
      fucosylated haptoglobin. Mass spectrometry analysis revealed the detailed
      oligosaccharide structure of fucosylated haptoglobin purified from sera of
      patients with pancreatic cancer. For clinical applications, we developed a lectin
      antibody ELISA system for quantifying fucosylated haptoglobin. In this review, we
      would like to summarize the history of the identification of fucosylated
      haptoglobin as a marker for pancreatic cancer and its possible application for a
      clinical diagnostic test.

PMID- 20816479
TI  - Differential glycan profiling by lectin microarray targeting tissue specimens.
AB  - Glycome is defined by the glycosylation machinery with which each cell is
      equipped, and this differs between species. It is evident that cells show drastic
      change during cell progression and differentiation associated with tumorigenesis
      and malformation. Histochemical approaches to analyze molecular and cellular
      dynamics provide useful clues to answering questions about glycan functions
      associated with pathology. However, development of glyco-biomarker discovery will
      require differential glycan analysis in a number of clinical specimens where
      disease lesions and normal regions from the same tissue sections are compared. In
      this chapter, we describe a simple but powerful method using an ultrasensitive
      lectin microarray, which enables rapid and systematic differential glycan
      analysis targeting restricted regions of formalin-fixed tissue specimens, for
      example, one-dot sections formatted on tissue arrays. Using this advanced
      technology followed by an objective statistical analysis, we can select lectin
      probes to best fit subsequent enrichment procedures to identify target
      glycoproteins that discriminate diseased and normal regions in the tissue
      specimens.

PMID- 20816480
TI  - A versatile technology for cellular glycomics using lectin microarray.
AB  - All cells in nature are covered with a dense and complex array of glycans. The
      total glycan repertoire expressed on cells, "the cellular glycome," varies at
      every level of biological organization, and in response to intrinsic and
      extrinsic stimuli. The cellular glycome is often referred to as the "cell face,"
      which reflects the condition and type of the cell. In other words, cells can be
      discriminated in detail by characterization of their individual cellular glycome.
      Based on this concept, we describe our strategy for profiling the cellular
      glycome using lectin microarray followed by lectin-based cell discrimination
      using Chinese hamster ovary cells and their glycosylation-defective mutants
      (Lec1, Lec2, and Lec8) as models. The results add to the understanding and
      applications of "Cellular Glycomics."

PMID- 20816481
TI  - Applications of heparin and heparan sulfate microarrays.
AB  - Carbohydrate microarrays have become crucial tools for revealing the biological
      interactions and functions of glycans, primarily because the microarray format
      enables the investigation of large numbers of carbohydrates at a time. Heparan
      sulfate (HS) and heparin are the most structurally complex glycosaminoglycans
      (GAGs). In this chapter, we describe the preparation of a small library of
      HS/heparin oligosaccharides, and the fabrication of HS/heparin microarrays that
      have been used to establish HS/heparin-binding profiles. Fibroblast growth
      factors (FGFs), natural cytotoxicity receptors (NCRs), and chemokines were
      screened to illuminate the very important biological functions of these glycans.

PMID- 20816482
TI  - Measurement of glycan-based interactions by frontal affinity chromatography and
      surface plasmon resonance.
AB  - Proteins and lipids are often modified with glycan chains, which due to their
      large hydration effect and structural heterogeneity, significantly alter the
      surface physicochemical properties of proteins and biomembranes. This "glyco
      atmosphere" also serves as a field for interactions with various molecules,
      including other glycans, lipids, peptides, proteins, and small molecules such as
      neurotransmitters and drugs as well as lectins. Therefore, sensitive techniques
      for measuring these glycan-based interactions are becoming more and more
      necessary, with the appropriate method largely depending on the interacting
      molecules. In this chapter, we focus on frontal affinity chromatography (FAC) and
      surface plasmon resonance (SPR) for examining polysialic acid-involved
      interactions with neurotransmitters and neurotrophins. FAC is characterized by
      its applicability to analyze weak interactions that are difficult to measure
      using conventional methods, and by the ease of principle and experimental
      procedures. SPR is advantageous due to the availability of suitable surface
      materials and for real-time monitoring with nonlabeled analytes.

PMID- 20816483
TI  - Detection of weak-binding sugar activity using membrane-based carbohydrates.
AB  - Protein-sugar interactions underlie many biological events. Although protein
      sugar interactions are weak, they are regulated in physiological conditions
      including clustering, association with other proteins, pH condition, and so on.
      The elucidation of the precise specificities of sugar-binding proteins is
      essential for understanding their biological functions. To detect the weak
      binding activity of carbohydrate-binding proteins to sugar ligands, we studied
      lectin tetramer binding to cell-surface carbohydrates by flow cytometry.
      Tetramerization of lectins enhanced their avidity for sugar ligands, and sugar
      chains displayed on the cell surfaces were easily accessible to such soluble
      lectins. In this chapter, we describe methods to (1) prepare biotinylated soluble
      lectin, (2) obtain R-phycoerythrin-labeled lectin tetramer, and (3) measure
      tetramer binding to various lectin-resistant cell lines or cells treated with
      sugar-processing inhibitors. This approach enabled us to detect the weak sugar
      binding activity of lectins (K(a) approximately 10(4)M(-1)), especially those
      from animals, and also to elucidate their specificity for sugar ligands.

PMID- 20816484
TI  - Fluorescence-based solid-phase assays to study glycan-binding protein
      interactions with glycoconjugates.
AB  - Development of glycan microarray technologies have recently revealed many new
      features in the binding specificities of glycan-binding proteins (GBPs) including
      animal and plant lectins, antibodies, toxins, and pathogens, including viruses
      and bacteria. Printed glycan microarrays are very sensitive, robust, and require
      very small quantities of glycans and GBPs. However, glycan arrays have been
      limited mostly to chemoenzymatically synthesized oligosaccharides and N-glycans
      isolated from natural glycoproteins. O-Glycans and more complex glycoconjugates,
      such as glycopeptides or whole cells, are generally lacking from most types of
      glycan microarrays. Certain GBPs such as selectins, that have more complex
      binding specificity, require peptide components besides the glycan structure for
      high-affinity binding to the ligand. GBP binding assays on glycan microarrays
      will provide only partial information about the specificity and high-affinity
      ligands for those GBPs. Therefore, more "natural" glycoconjugate arrays are
      required to study more complex GBP-glycoconjugate interactions. We have utilized
      a simple fluorescence-based solid-phase assay on a microplate format to study GBP
      glycoconjugate interactions. The method utilizes commercial streptavidin-coated
      microplates, where various biotinylated ligands, such as glycopeptides,
      oligosaccharides, and whole cells, can be immobilized at a defined density. The
      binding of GBPs to immobilized ligands can be studied using fluorescently labeled
      GBPs or cells, or bound GBPs can be detected using fluorescently labeled anti-GBP
      antibodies. Our approach utilizing biotinylated and fixed cells in a solid-phase
      assay is a versatile method to study binding of GBPs to natural cell-surface
      glycoconjugates. Not only mammalian cells, but also microorganisms can be
      biotinylated and fixed, and adhesion of fluorescently labeled GBPs and antibodies
      to immobilized cells can be studied using standard streptavidin-coated
      microplates. Here, we present examples of fluorescence-based solid-phase assays
      to study P- and L-selectin and galectin-1 binding to immobilized glycopeptides,
      oligosaccharides, and cells. It should be noted that with the availability of
      complex glycoconjugates containing available primary amine groups, such as
      semisynthetic glycopeptides described here, that these could also be printed on
      covalent microarrays for interrogation by GBPs.

PMID- 20816486
TI  - Imaging mass spectrometry of glycolipids.
AB  - Mass spectrometry (MS) is an analytical technique that separates ionized
      molecules using differences in their mass, and can be used to determine the
      structure of the molecules. Matrix-assisted laser desorption/ionization (MALDI)
      is one of the most commonly used ionization methods for this procedure. A new
      technical method, imaging mass spectrometry (IMS), which is a two-dimensional MS,
      enables molecular imaging of tissue sections by the use of the MALDI-MS method.
      In this chapter, we briefly discuss available methods for analyzing glycolipids
      by IMS. We describe sample detection strategies, and also introduce a
      representative example of its research application.

PMID- 20816485
TI  - Multifaceted approaches including neoglycolipid oligosaccharide microarrays to
      ligand discovery for malectin.
AB  - In this chapter, we describe the key procedures for isolation of the
      oligosaccharides and the preparation of neoglycolipid probes together with
      expression of malectin that have enabled the discovery of the highly selective
      binding of this newly described protein in the endoplasmic reticulum (ER) to a
      diglucosyl high-mannose N-glycan. This is the first indication of a bioactivity
      for a diglucosyl high-mannose N-glycan of the type that occurs in the ER of
      eukaryotic cells and which is an intermediate in the early steps of the N
      glycosylation pathway of nascent proteins. The malectin story is an example of a
      powerful convergence of disciplines in biological sciences: (i) developmental
      biology, (ii) bioinformatics, (iii) recombinant protein expression, (iv) protein
      structural studies, (v) glucan biochemistry, and (vi) drug-assisted engineering
      of oligosaccharide biosynthesis, culminating in (vii) oligosaccharide "designer"
      microarrays, to clinch the remarkable selectivity of the binding of this newly
      discovered ER protein. Thus, the way is open to the identification of the role of
      malectin in the N-glycosylation pathway.

PMID- 20816487
TI  - Dynamics and interactions of glycoconjugates probed by stable-isotope-assisted
      NMR spectroscopy.
AB  - Unique advantages offered by nuclear magnetic resonance (NMR) spectroscopy
      provide high-resolution information not only on structures but also on dynamics
      and interactions of glycoconjugates in solution. These benefits are further
      enhanced by applying stable-isotope-labeling techniques, which we have developed.
      Our stable-isotope-assisted NMR analyses of immunoglobulin G-Fc glycoproteins and
      the glycopeptides derived therefrom are here presented in terms of the dynamics
      and interactions of glycoconjugates.

PMID- 20816488
TI  - Self and nonself recognition with bacterial and animal glycans, surveys by
      synthetic chemistry.
AB  - In this chapter, we describe synthetic studies on partial structures of
      lipopolysaccharide (LPS) and peptidoglycan (PGN), which work as tags for nonself
      recognition in innate immune system. Our previous studies demonstrated that lipid
      A is the endotoxic principle of LPS. The synthetic homogeneous preparations have
      enabled not only precise structure-activity relationships, but also recognition
      mechanisms of LPS with innate immune receptor complexes, including the TLR4/MD-2
      complex, to be studied. Synthetic studies of lipid A and Kdo-lipid A from
      parasitic Helicobacter pylori revealed their low inflammatory activities,
      suggesting the molecular evolution to escape from the host immune system. A
      synthetic study of the partial structures of PGN has also contributed to the
      understanding of the innate immune mechanism. The biological activities of the
      synthetic fragments have revealed that the intracellular receptor Nod2 recognizes
      partial structures containing the muramyl dipeptide (MDP) moiety. The PGN of Gram
      negative bacteria and some Gram-positive bacteria contain meso-diaminopimelic
      acid (meso-DAP), and recent studies have revealed that the intracellular receptor
      Nod1 recognizes DAP-containing peptides. We have synthesized DAP-containing PGN
      fragments, including the first chemical synthesis of tracheal cytotoxin (TCT).
      The ability of these fragments to stimulate human Nod1 as well as differences in
      Nod1 recognition for various synthesized ligand structures was elucidated. Cell
      surface glycans such as N-glycans and O-glycans on glycoproteins and
      glycoconjugates work as signaling molecules for self-recognition and control
      immune system. Our new strategy using glycan-imaging in whole-body system is
      expected to unveil the dynamics of glycans in the body. Positron emission
      tomography (PET) is a noninvasive method that visualizes the locations and levels
      of radiotracer accumulation. We developed the facile labeling of peptides and
      proteins for PET imaging. The labeled glycoproteins and glycoclusters were then
      subjected to PET imaging in order to examine their in vivo dynamics, visualizing
      the differences in the circulatory residence of glycoproteins and glycoclusters
      in the presence or absence of sialic acid residues.

PMID- 20816489
TI  - Multivalent ligands for siglecs.
AB  - Siglecs have emerged as an important family of immunomodulatory glycan-binding
      proteins that can bind sialoside ligands both on the same cell surface, in cis,
      and on other cells, in trans. Expression of siglecs varies among a variety of
      immune cells, and tools to probe siglecs on these cells are crucial to
      understanding their function. In designing synthetic ligands, competition by cis
      ligands requires the use of multivalency to achieve sufficient avidity to stably
      bind siglecs on native cells. This chapter describes the use of multivalent
      ligands to probe cell surfaces, as well as to investigate ligand binding to
      recombinant siglecs.

PMID- 20816490
TI  - Intramolecular glycan-protein interactions in glycoproteins.
AB  - Glycoproteins are a major class of glycoconjugates displaying a variety of mutual
      interactions between glycan and protein moieties that ultimately affect molecular
      organization. Modulation of the pendant glycan structures is important in tuning
      the functions of glycoproteins. Here we discuss structural aspects and some of
      the challenges to studying intramolecular interactions between carbohydrate and
      protein elements in several forms of O-linked as well as N-linked glycoproteins.
      These illustrate the importance of the relationship of context to function in
      protein glycosylation.

PMID- 20816491
TI  - Methods to study the biosynthesis of bacterial furanosides.
AB  - Carbohydrates in the thermodynamically disfavored furanose ring conformation are
      not present in mammalian glycoconjugates, but are widespread in the glycans
      produced by many bacterial pathogens. In bacteria, these furanose sugars are
      often found in cell surface glycoconjugates, and are essential for the viability
      or virulence of the organisms. As a result, the enzymes involved in the
      biosynthesis of bacterial furanosides are attractive targets as potential
      selective antimicrobial chemotherapeutics. However, before such chemotherapeutics
      can be designed, synthesized, and evaluated, more information about the activity
      and specificity of these enzymes is required. This chapter describes assays that
      have been used to study enzymes involved in the biosynthesis of one of the most
      abundant naturally occurring furanose residues, galactofuranose (Galf). In
      particular, the focus is on UDP-galactopyranose mutase and
      galactofuranosyltransferases. The assays described in this chapter require UDP
      galactofuranose (UDP-Galf); therefore, a procedure for the preparation of UDP
      Galf, as well as various UDP-Galf derivatives, using a three-enzyme
      chemoenzymatic procedure, is also described.

PMID- 20816492
TI  - The synthesis of 1,2-cis-amino containing oligosaccharides toward biological
      investigation.
AB  - 1,2-cis-Aminoglycoside structure is frequently found in bioactive
      oligosaccharide. In this chapter, the recent development of 1,2-cis
      aminoglycoside preparation is described. The interface investigations between
      biology and chemistry with using synthetic oligosaccharides are also described.

PMID- 20816493
TI  - Aminoglycosides redesign strategies for improved antibiotics and compounds for
      treatment of human genetic diseases.
AB  - Aminoglycosides are highly potent, broad-spectrum antibiotics that kill bacteria
      by binding to the ribosomal decoding site and reducing the fidelity of protein
      synthesis. The emergence of bacterial strains resistant to these drugs, as well
      as their relative toxicity, have inspired extensive searches toward the goal of
      obtaining novel molecular designs with improved antibacterial activity and
      reduced toxicity. In recent years, a new therapeutic approach that employs the
      ability of certain aminoglycosides to induce mammalian ribosomes to readthrough
      premature stop codon mutations has emerged. This new and challenging task has
      introduced fresh research avenues in the field of aminoglycosides research. In
      this chapter, our recent observations and current challenges in the design of
      aminoglycosides with improved antibacterial activity and the treatment of human
      genetic diseases are discussed.

PMID- 20816494
TI  - Solid phase synthesis of oligosaccharides.
AB  - Oligosaccharides are involved in many fundamental biological processes. However,
      relatively little is known about the precise molecular mechanism of action of
      these macromolecules, because the complexity of these structures impeded their
      synthesis by chemical methods analogous to those employed to create
      oligonucleotides and peptides. Herein, we describe recently developed techniques
      for solid-supported oligosaccharide synthesis. Several key aspects of solid phase
      synthesis are highlighted and examined, including the choice of resin and the
      challenge of real-time reaction monitoring. Recent examples of manual and
      automated solid-supported syntheses of complex oligosaccharides are given and the
      automated solid phase synthesis of the tumor-associated carbohydrate antigen
      Globo-H is highlighted.

PMID- 20816495
TI  - Novel synthesis of functional mucin glycopeptides containing both N- and O
      glycans.
AB  - Progress of synthetic methods using ligation makes it possible to access larger
      and multifunctionalized biomolecules. Recently, sortase-mediated ligation was
      used as a new and complementary technique for construction of peptide and protein
      to other ligation methods. Staphylococcus aureus Sortase A (SrtA) is a
      transpeptidase that recognizes C-terminal LPXTG motif of proteins to cleave
      between T and G, and subsequently transfers the acyl component to a nucleophile
      containing N-terminal oligo-glycines. Toward development of multi- and
      heteroglycosylated protein synthesis, we utilized SrtA-mediated ligation
      technique for preparation of MUC1-related glycopeptide analogs having both N- and
      O-glycans as model compounds. To further improve this synthetic strategy, we also
      demonstrated the merits of SrtA-mediated ligation by means of a polymer-supported
      protocol. The present strategy will facilitate rapid and large-scale synthesis of
      multiply functionalized neoglycoprotein as new types of convenient models for the
      investigation of structure-function relationship.

PMID- 20816496
TI  - Synthesis of glycopeptides.
AB  - Oligosaccharides in protein play important roles in several biological events. In
      order to investigate the functions of oligosaccharides of protein, glycoproteins
      having homogeneous oligosaccharides should be prepared. For this purpose,
      preparation methods of diverse complex-type oligosaccharides as well as synthetic
      methods of glycopeptides are essential. This report describes the recent progress
      in the synthesis of glycopeptides having homogeneous complex-type
      sialyloligosaccharides.

PMID- 20816497
TI  - Renewed synthetic approach to gangliosides exploiting versatile and powerful
      synthetic units.
AB  - It is well known that gangliosides, sialic acid-containing glycosphingolipids,
      play important roles in diverse biological processes associated with cell
      development, immune response, cancer metastasis, infection, and signal
      transduction. Synthetic chemistry of ganglioside has been promoting the
      elucidation of the ganglioside functions at the molecular level by the supply of
      homogenous gangliosides and their functional probes. For advancing further
      glycobiology, synthetic chemistry of ganglioside must be elaborated to be capable
      of producing a large supply of gangliosides. Recent innovation of sialic acid
      chemistry allowed to access to sialic acid-containing oligosaccharides. This
      chapter will focus on new approaches toward the efficient total synthesis of
      gangliosides.

PMID- 20816498
TI  - Metabolic labeling of glycoconjugates with photocrosslinking sugars.
AB  - Protein-carbohydrate interactions play essential roles in a variety of biological
      processes. This class of interactions is particularly important in development,
      immunology, infection, and carcinogenesis. However, the transient nature of
      glycan-dependent interactions hampers efforts to detect and characterize these
      complexes. Photocrosslinking is emerging as a powerful tool to discover and study
      glycan-dependent complexes. Through the use of photocrosslinking groups, UV
      irradiation can be employed to introduce a covalent bond between two transiently
      interacting molecules. Here we describe the use of metabolic oligosaccharide
      engineering to incorporate a photocrosslinkable sugar into cellular
      glycoconjugates and the use of this photocrosslinker to covalently capture glycan
      mediated interactions.

PMID- 20816499
TI  - Identification of carbohydrate-binding proteins by carbohydrate mimicry peptides.
AB  - Peptide-displaying phage technology has numerous applications. Using a
      specificity-defined monoclonal anticarbohydrate antibody, we can identify a
      series of short peptides that mimic the binding specificity of a specific
      carbohydrate. Identified peptides constitute alternatives to the use of
      carbohydrate ligands in affinity chromatography to isolate a carbohydrate-binding
      protein. In this chapter, we introduce methods for carbohydrate mimicry peptide
      affinity chromatographies and discuss their potential use in identifying yet
      undiscovered carbohydrate-binding proteins in normal and pathological conditions.

PMID- 20816500
TI  - Surgically unresectable regional melanoma metastases in a patient with renal
      failure and peripheral vascular disease: are there safe and potentially effective
      treatments?

PMID- 20816501
TI  - Mucinous adenocarcinoma of the ovary.

PMID- 20816502
TI  - Cancer Prevention II: Introduction.

PMID- 20816504
TI  - Further thoughts on preclinical animal models for cancer prevention: when is it
      best to start treatment? What are potential histopathologic endpoints?
AB  - One of the major questions in preclinical testing of potential cancer preventive
      agents is how to most closely approximate the testing protocol to be employed in
      phase III prevention trials. The nature of tumors arising in situ in animals
      allows one to initiate agent exposure from the time of tumor initiation until the
      time that preinvasive lesions already exist. The large phase III prevention
      trials have routinely followed participants for 3 to 7 years until a cancer
      endpoint, which generally implies that the timing of the intervention occurs
      further along during tumor progression. The objective of preclinical testing is
      to identify agents for large-scale phase III trials. Accordingly, initiating the
      tested intervention in preclinical studies later in the tumor progression process
      is more appropriate for any agent being proposed for phase III clinical trials.
      Furthermore, cancer, rather than advanced dysplastic lesions or other molecular
      markers (gene or protein expression), is the preferred primary endpoint. However,
      simultaneous examination of earlier designated "intermediate" endpoints
      (hyperplasias, dysplasias, or molecular markers) to determine whether their
      modulation correlates with that of the primary tumor endpoint would be useful,
      since these latter endpoints may be employed in phase II prevention trials.

PMID- 20816503
TI  - The use of animal models for cancer chemoprevention drug development.
AB  - Animal models currently are used to assess the efficacy of potential
      chemopreventive agents, including synthetic chemicals, chemical agents obtained
      from natural products, and natural product mixtures. The observations made in
      these models as well as other data are then used to prioritize agents to
      determine which are qualified to progress to clinical chemoprevention trials.
      Organ-specific animal models are employed to determine which agents or classes of
      agents are likely to be the most effective at nontoxic doses to prevent organ
      specific forms of cancer. These results are then used to target specific organs
      in high-risk populations in clinical trials. The animal models used are either
      carcinogen-induced with carcinogens specific for particular organ sites or they
      are transgenic/mutant animals with insertions, deletions, or mutations at
      targeted gene sites known to enhance cancers in a specific organ. Animal tumor
      models with characteristics favorable to chemoprevention studies are available
      for cancers of the lung, colon, skin, bladder, mammary, prostate, head and neck,
      esophagus, ovary, and pancreas. In addition to single-agent dose-response
      testing, such models are frequently used for testing combinations of agents,
      testing different routes of administration, evaluating surrogate endpoint
      biomarkers, and generating initial pharmacokinetics and toxicology data. For some
      of the more standard animal models there is significant correlation with human
      chemopreventive trial results. There are a growing number of positive human
      chemoprevention trials that have used agents or combinations that were positive
      in animal testing. There have been fewer negative human clinical trials, but
      their results again correlate with negative animal results. Clearly the
      validation of animal models to predict the efficacy of agents in human clinical
      trials will await further human data on positive and negative outcomes with
      chemopreventive agents. Whether validated or not, animal efficacy data remain
      central to the clinical trial decision-making process.

PMID- 20816505
TI  - Drug development for cancer chemoprevention: focus on molecular targets.
AB  - With biomolecular evidence accumulating at an exponential rate, there will be a
      surge in the development of targeted cancer prevention drugs and interventions in
      the next decade. Promising results from clinical treatment trials identify a
      spectrum of targeted cancer therapies in several broad categories. These include
      both small molecule inhibitors of either key receptors or enzyme binding sites,
      as well as intravenously delivered monoclonal antibodies that block a specific
      binding interaction between ligands and their receptors. These targeted
      interventions conform to a basic translational algorithm: biomarker present,
      biomarker modulated, and biomarker clinically relevant. A review of solid tumor
      targets provides a manageable list of factors that are critical to cancer cell
      survival. As such, these targets represent factors that are not only clinically
      relevant but also may play a critical role in early tumor development prior to
      the evolution of frank invasive malignancy. This possibility qualifies these
      targets for consideration in the development of cancer prevention interventions.
      Among solid tumors, the treatment of breast cancer with targeted drugs has a long
      record benchmarked by the initial US Food and Drug Administation (FDA) approval
      of tamoxifen for metastatic breast cancer treatment in 1977. Since then, the list
      of oncology drug targets has expanded to include aromatase, androgen receptor,
      the epidermal growth factor receptor (EGFR) family, and others. It is not
      surprising that tamoxifen was the first of the modern targeted therapies to be
      approved for cancer risk reduction and additional approvals are anticipated. The
      focus of this review is the pharmacologic manipulation of targets within
      epithelial tumor cells and the implication of those targets for intervening to
      suppress and eliminate premalignant cells in human tissue. Major obstacles to
      prevention drug development can be addressed by attention to two important areas.
      One of these is the refinement of early phase prevention trials to identify drug
      targets in epithelial cells that are at demonstrated risk of evolving into cancer
      cells, ie, cells from a developmental niche in cancer ontogeny. Early results
      suggest that molecular risk signatures may allow the investigational
      identification of molecular targets in premalignant tissue, with the possibility
      that chemoprevention agents can be used to eliminate the risk signature. To the
      extent that this approach can be developed, it will allow for cancer risk
      reduction in a way that is analogous to the measurement of tumor response to
      treatment. Even with improvements in the efficiency of clinical trials that come
      from using molecular risk signatures, there is an ever-growing list of
      chemoprevention agents that are candidates for evaluation. Improved prevention
      drug screening methodologies are therefore needed to prioritize agents for
      clinical testing. In addition to drug targets located in epithelial tumor cells,
      another list of malignancy-associated targets could be generated by considering
      targets in tumor-associated stromal and endothelial cells (eg, fibroblast growth
      factor [FGF], vascular endothelial growth factor [VEGF]), as well as targets
      related to a systemic reservoir of circulating cells that can be recruited to
      carcinogenic influence by inflammatory factors such as nuclear factor (NF)kappaB.
      The complementarities of target-related processes within tumors cells, in the
      tumor microenvironment, and beyond suggests that there is great potential for
      multi-targeted approaches that may be more effective than single agents and also
      less prone to resistance. Additional options, related to drug dose and schedule,
      remain to be established. As long as multiple agents can be used in combination
      for optimal effect with acceptable toxicity, the co-targeting of the epithelial
      cell compartment along with other compartments of oncogenic activity is expected
      to expand the dimensions of targeted prevention and enhance the overall
      opportunity to eliminate precancer or cells at risk of eventually transitioning
      to invasive cancer.

PMID- 20816507
TI  - Breast cancer prevention trials: large and small trials.
AB  - Breast cancer is the most common cancer among women in the United States, with
      192,870 new cases and 40,170 deaths due to this disease estimated to have
      occurred 2009. An emphasis on prevention has been increasing in view of a
      persisting high incidence of disease. Seventy percent of breast cancers are
      estrogen receptor (ER)-positive, and are therefore presumed to be hormone
      responsive and potentially treatable or preventable by anti-estrogenic agents. To
      date, the large, phase III randomized controlled breast cancer prevention trials
      have tested and are testing only hormonal drugs designed to antagonize the
      carcinogenic effect of endogenous estrogen; these agents are either selective
      estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs). The SERMs,
      tamoxifen and raloxifene, have been shown in these large trials to reduce the
      risk of ER-positive breast cancers; prevention trials of AIs are ongoing.
      Interest is now focusing on developing agents with a broader spectrum of
      preventive activity, particularly with regard to ER-negative subtypes of breast
      cancer. A number of phase I and II trials using tissue-derived surrogate endpoint
      biomarkers (SEBs) as outcomes have been implemented. These smaller trials address
      prevention not only of ER-negative but also ER-positive breast cancers, since
      approximately 50% of the latter have been shown to be resistant to the estrogen
      targeting drugs used in the large trials. Issues of importance in these smaller
      trials include choice of agent, selection of appropriate trial participants,
      trial design, method of access to breast tissue in women without cancer,
      selection and monitoring of SEBs, and monitoring of drug toxicity.

PMID- 20816506
TI  - Phase II cancer prevention clinical trials.
AB  - The development of agents to prevent cancer requires an iterative process of
      target identification, preclinical testing, and early and late phase clinical
      trials to establish efficacy and safety. Since phase III definitive efficacy
      trials with cancer endpoints require a lengthy timeframe and considerable
      resources for completion, it is critical to first optimize agent delivery and
      trial design and to determine preliminary efficacy via the conduct of phase II
      trials. Phase II trials vary considerably in their endpoints, cohorts, and
      designs due to differences in the process of carcinogenesis and ability to sample
      tissues across different target organs. However, the goal of all such trials is
      to provide evidence of interference with the development of cancer and to
      identify safety signals that would limit the benefit from interventions.

PMID- 20816508
TI  - Epidemiology of health disparities in relation to the biology of estrogen
      receptor-negative breast cancer.
AB  - Breast cancer is the most common cancer in women worldwide, accounting for just
      over 1 million new cases annually. Population-based statistics show that
      globally, when compared to whites, women of African ancestry tend to have more
      aggressive breast cancers that present more frequently as estrogen receptor
      negative (ER(-)) tumors. ER(-) tumors fail to respond to current established
      targeted therapies, whether for treatment or prevention. Subsets of the ER(-)
      phenotype include those that are also negative for the progesterone receptor (PR)
      and human epidermal growth factor receptor (HER2); these are called "triple
      negative" (TN) breast cancers. The ER(-), TN, and basal-like phenotypic
      categories are important because they carry worse prognoses than estrogen
      receptor-positive (ER(+)) tumors, in addition to lacking obvious molecular
      targets for known therapies. Furthermore, among premenopausal women, the three
      subsets occur more frequently in women of African descent compared to white women
      with breast cancer. The contribution of these three subtypes of poor-prognosis
      tumors to the higher breast cancer mortality in black women is the focus of this
      review. Epidemiologic and lifestyle risk factors such as diet and physical
      activity and ER(-) breast cancer risk are reviewed. We will attempt to clarify
      some of the issues, in terms of their contribution to that component of health
      disparities that involves biological differences in breast cancer between women
      of African ancestry and white women.

PMID- 20816509
TI  - Conducting chemoprevention clinical trials: challenges and solutions.
AB  - The clinical trials investigative team faces a number of challenges during the
      execution of a chemoprevention protocol that often depend on the phase of the
      trial. Phase II chemoprevention trials test promising agents for biomarker
      modulation in cohorts of 30 to 200 participants at greater than average risk of
      the cancer being studied who meet strict eligibility criteria. By contrast, phase
      III trials test agents for their efficacy in cancer prevention in thousands of
      participants who are generally healthy or may be at slightly elevated risk.
      Consideration must be given to accruing a very large cohort or a smaller but
      relatively rare group of participants, and to maintaining vigilance over the
      toxicity profile of the agent, which may be taken for a lengthy period of time.
      Additional considerations include clear communication to the participants of the
      risks and benefits associated with participating on the trial, as well as the
      need for their long-term commitment. In light of the layer of complexities that
      chemoprevention research adds to clinical trials, one or more team members need a
      unique set of skills and knowledge, beyond understanding the scientific aspects
      of the trial.

PMID- 20816510
TI  - The application of genetics and genomics to cancer prevention.
AB  - Advances in technology have accelerated the translation of genetics and genomics
      into the arena of cancer prevention. This provides unique opportunities to
      individualize cancer risk prediction so early intervention can either modify risk
      or allow for early diagnosis thereby potentially decreasing the morbidity and
      mortality of cancer and containing costs. While the full potential of these
      genetic/genomic discoveries have yet to be realized, many have clear clinical
      relevance such as the value of family history and/or tumor profiling to identify
      those who may harbor a mutation in a cancer susceptibility gene and are therefore
      candidates for genetic testing. Here, we provide an overview of the scope of
      genetic and genomic influences on cancer risk assessment and the entire spectrum
      of cancer prevention.

PMID- 20816511
TI  - The use of DIEAP flaps in postmastectomy breast reconstruction is a case in
      point. Preface.

PMID- 20816512
TI  - The anatomic basis of perforator flaps.
AB  - The recent enthusiasm for perforator flaps underlines the need for a detailed
      understanding of the cutaneous vasculature. The principle determinant of success
      in perforator flap surgery is the inclusion of an adequately sized cutaneous
      perforator in the flap. Therefore, the size, distribution, and variability of
      cutaneous perforators of the human body are crucial to the design and execution
      of successful perforator flap surgery. Based on numerous anatomic studies, the
      authors have found that the main source arteries supplying the skin are fairly
      constant but the individual cutaneous perforators are quite variable. Knowledge
      of the overall architecture of the vasculature and an awareness of the
      variability, combined with a flexible operative plan, will enable the perforator
      flap surgeon to take advantage of the most appropriate perforators to execute a
      successful operative plan.

PMID- 20816513
TI  - Where do perforator flaps fit in our armamentarium?
AB  - This article reviews historical aspects of flap development, leading up to the
      exciting recognition of perforator flaps. The role and use of perforator-type
      flaps in the reconstructive armamentarium is reviewed as it pertains to different
      regions of the body.

PMID- 20816514
TI  - Preoperative imaging techniques for perforator selection in abdomen-based
      microsurgical breast reconstruction.
AB  - The clinical application of perforator-based flaps for microsurgical breast
      reconstruction has increased exponentially over the past 10 years. The benefits
      of the procedure are thought to be that it produces less postoperative pain,
      lowers abdominal morbidity, and allows for better preservation of muscles at the
      donor site compared with conventional musculocutaneous flaps. The disadvantages
      of perforator flaps are that they are more difficult to harvest, which can result
      in a longer operative time and higher costs. The vascular anatomy of the deep
      inferior epigastric artery and its perforating branches in the abdominal wall
      varies greatly not only among individuals but also from one side of the abdomen
      to the other. Perforator location, number, caliber, and the intramuscular
      trajectory of the branches all impact the design and harvest of the flap. The
      creation of a presurgical map of the vessels on the abdomen can facilitate
      surgical planning and could decrease operating room time, reduce intraoperative
      complications, and lead to improved outcomes. This article reviews the available
      techniques for preoperative planning with the currently available imaging
      modalities: hand-held Doppler, color Doppler (duplex) ultrasound, CT angiography,
      and MR angiography.

PMID- 20816515
TI  - Technical tips for safe perforator vessel dissection applicable to all perforator
      flaps.
AB  - The introduction of perforator flaps by Koshima and Soeda in 1989 was met with
      much animosity in the surgical community. The flaps challenged conventional
      teaching and were often branded as being unsafe. Surgeries using perforator flaps
      are now routinely practiced all over the world, with increasing emphasis on
      minimizing donor site morbidity, and perforator flaps are becoming the current
      gold standard. The simple principles and techniques of perforator dissection can
      be applied to all perforator flaps, provided the surgeon has an intimate
      knowledge of the regional anatomy. Thus, virtually any piece of skin can be
      harvested as long as it incorporates a feeding vessel. This article highlights
      the essential techniques in planning and raising perforator flaps and the common
      pitfalls to be avoided.

PMID- 20816516
TI  - The integration of muscle perforator flaps into a community-based private
      practice.
AB  - Over the past decade, muscle perforator flaps have proven their versatility as
      another important option when a soft tissue flap is essential. Valuable as either
      local or free flaps, these are no longer a novelty, and are perhaps even becoming
      a necessity for the mainstream reconstructive surgeon. Prior microsurgical
      capabilities will unquestionably simplify the transition to harvesting the
      diminutive vascular pedicle of these flaps, while perhaps shortening the learning
      curve, but these skills are not imperative. With proper assistance and
      perseverance, as with any other aspect of surgery, muscle perforator flaps can
      become a mainstay, if not the preferred method, for soft tissue repairs even in
      the community hospital where resources tend to be less available.

PMID- 20816517
TI  - The propeller flap concept.
AB  - The propeller flap, based on a single vascular pedicle supplying a
      fasciocutaneous island of skin, is a very useful technique to reconstruct soft
      tissue defects and has wide applications throughout the body. The use of this
      unique flap is pushing the boundaries of local flap reconstruction and bringing
      up intriguing questions about our understanding of the vascular basis of
      fasciocutaneous flaps.

PMID- 20816518
TI  - Pedicled perforator flaps in the head and neck.
AB  - Perforator flaps, since their first description in 1989, have in many ways
      revolutionized reconstructive surgery. Whereas little more than a decade ago many
      surgeons were still hesitant to fully trust perforator flaps to be a reliable
      option, nowadays these flaps are often first choice. Investigators have to remain
      critical, however, of their advances and realize that not every reconstruction
      will require or benefit from a perforator flap, as previously well-established,
      nonperforator flaps still have their indication and can give excellent results.
      The most important skill in reconstructive surgery of the head and neck is not
      cutting the flap but assessing the defect, planning the reconstruction, and
      choosing wisely from the ever-increasing options available.

PMID- 20816519
TI  - Perforator flaps in breast reconstruction.
AB  - Patients are well informed and seek autogenous breast reconstruction. The
      motivating factors include a preference for autologous tissue reconstruction and
      the complementary improvement in body contour, safety concerns surrounding
      implants, and implant-related complications in the setting of previous radiation
      therapy. In this article a variety of perforator flaps from donor sites that
      include the trunk (thoracodorsal artery perforator and intercostal artery
      perforator), abdomen (deep inferior epigastric artery perforator and superficial
      inferior epigastric artery), and buttock (superior gluteal artery perforator and
      inferior gluteal artery perforator) are described. Flaps from the trunk can be
      pedicled for partial breast reconstruction, and free flaps from the other donor
      sites can completely restore a natural-looking breast. The information obtained
      from preoperative CT and MRI can direct the surgeon toward the most successful
      operative plan. However, the decision as to which flap may be most appropriate
      for an individual patient is complex. This article reviews pertinent surgical
      anatomy, preoperative planning, intraoperative decision making in flap elevation,
      and reported outcomes.

PMID- 20816520
TI  - Pedicled perforator flaps in the trunk.
AB  - Trunk defects can be approached through a multitude of regional flaps that can be
      harvested from the shoulder girdle, the epigastric axis, the paraspinal region,
      or the pelvic girdle. The aim of the reconstruction is to provide adequate and
      tension-free restoration of tissue integrity with minimal functional morbidity,
      water- and airtight closure of cavities, and coverage of exposed vital
      structures. Potential donor sites should be estimated for their tissue quality
      and anticipated donor site morbidity. The prototypical pedicled flap has a
      constant, reliable anatomy; however, the pedicled flap should have a
      configuration that is versatile and adequate for coverage and should resist
      infection. Also, the surgical technique should be uncomplicated.

PMID- 20816521
TI  - Perforator flaps in the upper extremity.
AB  - Perforator flaps are frequently used for defect coverage for the whole body.
      There are strong indications for the use of perforator flaps in the upper
      extremity. This article demonstrates the possibilities for defect coverage with
      perforator flaps as well as their anatomic and technical considerations. Lateral
      arm, posterior interosseous artery, ulnar artery, radial artery perforator flaps,
      and intrinsic hand flaps are described.

PMID- 20816522
TI  - Versatility of the pedicled anterolateral thigh flap.
AB  - The pedicled anterolateral thigh flap is a useful addition to our armamentarium.
      It provides excellent cover for defects in the lower abdomen, pelvis, and
      perineum. It also has the added advantage of not sacrificing any muscle, thereby
      minimizing the risk for donor morbidity. This article reviews the major
      applications of the proximally pedicled anterolateral thigh flap, describes the
      technique of flap harvest, and discusses techniques of flap transposition as well
      as pointing out some potential hazards.

PMID- 20816523
TI  - Perforator flaps and supermicrosurgery.
AB  - The introduction of supermicrosurgery, which allows the anastomosis of smaller
      caliber vessels and microvascular dissection of vessels ranging from 0.3 to 0.8mm
      in diameter, has led to the development of new reconstructive techniques. New
      applications of this technique are for crushed fingertip replantations with
      venule grafts, toe tip transfers for fingertip loss, partial auricular transfers
      for total tracheal and eyelid defects, and lymphaticovenular anastomoses under
      local anesthesia for lymphedema. Regarding free flaps, free perforator-to
      perforator flaps, including deep inferior epigastric perforator or paraumbilical
      perforator flaps, gluteal artery perforator flaps, thoracodorsal artery
      perforator flaps, anterolateral thigh perforator flaps, superficial circumflex
      iliac artery perforator flaps, tensor fasciae lata perforator flaps, and medial
      plantar perforator flaps, with a short pedicle, have been used for extremity and
      facial defects. The success rate is almost the same as that of usual free flap
      transfers with large and long pedicles. The advantages of these flaps are the
      simple operation and the short time needed for flap elevation, plus the fact that
      the flaps can be obtained from anywhere in concealed areas. The disadvantages are
      the need for supermicrosurgical technique and the anatomic variation of these
      perforators.

PMID- 20816524
TI  - Physician, know thyself.

PMID- 20816525
TI  - Perils of asthma research in vulnerable groups.

PMID- 20816526
TI  - Stigmatisation of problem-drug users.

PMID- 20816527
TI  - Perioperative respiratory complications in children.

PMID- 20816528
TI  - Refractory breathlessness: oxygen or room air?

PMID- 20816529
TI  - Call for withdrawal of LABA single-therapy inhaler in asthma.

PMID- 20816530
TI  - The impact of asthma guidelines.

PMID- 20816531
TI  - The year of the lung.

PMID- 20816532
TI  - Tracking radiation exposure of patients.

PMID- 20816534
TI  - Heather Zar--improving lung health for children in Africa.

PMID- 20816535
TI  - Community-associated meticillin-resistant Staphylococcus aureus.

PMID- 20816537
TI  - Community-associated meticillin-resistant Staphylococcus aureus.

PMID- 20816538
TI  - Antitrypanosomal agents: treatment or threat?

PMID- 20816540
TI  - The international study of insulin and cancer.

PMID- 20816541
TI  - Cause-of-death data to support MDG 4 progress.

PMID- 20816542
TI  - The Lancet-Palestinian Health Alliance.

PMID- 20816543
TI  - NICE guidelines on neonatal jaundice: at risk of being too nice.

PMID- 20816544
TI  - The Lancet-Palestinian Health Alliance.

PMID- 20816545
TI  - Risk assessment for respiratory complications in paediatric anaesthesia: a
      prospective cohort study.
AB  - BACKGROUND: Perioperative respiratory adverse events in children are one of the
      major causes of morbidity and mortality during paediatric anaesthesia. We aimed
      to identify associations between family history, anaesthesia management, and
      occurrence of perioperative respiratory adverse events. METHODS: We prospectively
      included all children who had general anaesthesia for surgical or medical
      interventions, elective or urgent procedures at Princess Margaret Hospital for
      Children, Perth, Australia, from Feb 1, 2007, to Jan 31, 2008. On the day of
      surgery, anaesthetists in charge of paediatric patients completed an adapted
      version of the International Study Group for Asthma and Allergies in Childhood
      questionnaire. We collected data on family medical history of asthma, atopy,
      allergy, upper respiratory tract infection, and passive smoking. Anaesthesia
      management and all perioperative respiratory adverse events were recorded.
      FINDINGS: 9297 questionnaires were available for analysis. A positive respiratory
      history (nocturnal dry cough, wheezing during exercise, wheezing more than three
      times in the past 12 months, or a history of present or past eczema) was
      associated with an increased risk for bronchospasm (relative risk [RR] 8.46, 95%
      CI 6.18-11.59; p<0.0001), laryngospasm (4.13, 3.37-5.08; p<0.0001), and
      perioperative cough, desaturation, or airway obstruction (3.05, 2.76-3.37;
      p<0.0001). Upper respiratory tract infection was associated with an increased
      risk for perioperative respiratory adverse events only when symptoms were present
      (RR 2.05, 95% CI 1.82-2.31; p<0.0001) or less than 2 weeks before the procedure
      (2.34, 2.07-2.66; p<0.0001), whereas symptoms of upper respiratory tract
      infection 2-4 weeks before the procedure significantly lowered the incidence of
      perioperative respiratory adverse events (0.66, 0.53-0.81; p<0.0001). A history
      of at least two family members having asthma, atopy, or smoking increased the
      risk for perioperative respiratory adverse events (all p<0.0001). Risk was lower
      with intravenous induction compared with inhalational induction (all p<0.0001),
      inhalational compared with intravenous maintenance of anaesthesia (all p<0.0001),
      airway management by a specialist paediatric anaesthetist compared with a
      registrar (all p<0.0001), and use of face mask compared with tracheal intubation
      (all p<0.0001). INTERPRETATION: Children at high risk for perioperative
      respiratory adverse events could be systematically identified at the
      preanaesthetic assessment and thus can benefit from a specifically targeted
      anaesthesia management. FUNDING: Department of Anaesthesia, Princess Margaret
      Hospital for Children, Swiss Foundation for Grants in Biology and Medicine, and
      the Voluntary Academic Society Basel.

PMID- 20816546
TI  - Effect of palliative oxygen versus room air in relief of breathlessness in
      patients with refractory dyspnoea: a double-blind, randomised controlled trial.
AB  - BACKGROUND: Palliative oxygen therapy is widely used for treatment of dyspnoea in
      individuals with life-limiting illness who are ineligible for long-term oxygen
      therapy. We assessed the effectiveness of oxygen compared with room air delivered
      by nasal cannula for relief of breathlessness in this population of patients.
      METHODS: Adults from outpatient clinics at nine sites in Australia, the USA, and
      the UK were eligible for enrolment in this double-blind, randomised controlled
      trial if they had life-limiting illness, refractory dyspnoea, and partial
      pressure of oxygen in arterial blood (PaO(2)) more than 7.3 kPa. Participants
      were randomly assigned in a 1:1 ratio by a central computer-generated system to
      receive oxygen or room air via a concentrator through a nasal cannula at 2 L per
      min for 7 days. Participants were instructed to use the concentrator for at least
      15 h per day. The randomisation sequence was stratified by baseline PaO(2) with
      balanced blocks of four patients. The primary outcome measure was breathlessness
      (0-10 numerical rating scale [NRS]), measured twice a day (morning and evening).
      All randomised patients who completed an assessment were included in the primary
      analysis for that data point (no data were imputed). This study is registered,
      numbers NCT00327873 and ISRCTN67448752. FINDINGS: 239 participants were randomly
      assigned to treatment (oxygen, n=120; room air, n=119). 112 (93%) patients
      assigned to receive oxygen and 99 (83%) assigned to receive room air completed
      all 7 days of assessments. From baseline to day 6, mean morning breathlessness
      changed by -0.9 points (95% CI -1.3 to -0.5) in patients assigned to receive
      oxygen and by -0.7 points (-1.2 to -0.2) in patients assigned to receive room air
      (p=0.504). Mean evening breathlessness changed by -0.3 points (-0.7 to 0.1) in
      the oxygen group and by -0.5 (-0.9 to -0.1) in the room air group (p=0.554). The
      frequency of side-effects did not differ between groups. Extreme drowsiness was
      reported by 12 (10%) of 116 patients assigned to receive oxygen compared with 14
      (13%) of 108 patients assigned to receive room air. Two (2%) patients in the
      oxygen group reported extreme symptoms of nasal irritation compared with seven
      (6%) in the room air group. One patient reported an extremely troublesome nose
      bleed (oxygen group). INTERPRETATION: Since oxygen delivered by a nasal cannula
      provides no additional symptomatic benefit for relief of refractory dyspnoea in
      patients with life-limiting illness compared with room air, less burdensome
      strategies should be considered after brief assessment of the effect of oxygen
      therapy on the individual patient. FUNDING: US National Institutes of Health,
      Australian National Health and Medical Research Council, Duke Institute for Care
      at the End of Life, and Doris Duke Charitable Foundation.

PMID- 20816547
TI  - Asthma in older adults.
AB  - Asthma in older people is common and is characterised by underdiagnosis and
      undertreatment. Ageing is associated with unique issues that modify expression,
      recognition, and treatment of the disease. In particular, asthma and chronic
      obstructive pulmonary disease (COPD) both overlap and converge in older people.
      This concurrence, together with absence of precise diagnostic methods, makes
      diagnosis complex. A multidimensional assessment that addresses airway problems,
      comorbidities, risk factors, and management skills will draw attention to key
      needs for intervention. Increased attention to the complications of asthma and
      obstructive airway disease in older people is needed, specifically to develop
      effective systems of care, appropriate clinical practice guidelines, and a
      research agenda that delivers improved health outcomes.

PMID- 20816550
TI  - The role of dendritic and epithelial cells as master regulators of allergic
      airway inflammation.
AB  - Lung dendritic cells bridge innate and adaptive immunity, integrating a variety
      of stimuli from allergens, microbial colonisation, environmental pollution, and
      innate immune cells into a signal for T lymphocytes of the adaptive immune
      system. Dendritic cells have a pivotal role in the activation of T helper (Th) 2
      cells and allergic inflammation. Lung dendritic cells can also prevent harmful
      immune responses to innocuous inhaled antigens via induction of regulatory T
      cells or Th1 cells. In our Review, we discuss how understanding the biology of
      dendritic cells is crucial for understanding the interaction between allergens,
      the environment, and genetics, and focus on how dendritic cells conspire with
      airway epithelial cells and innate pro-Th2 cells to cause allergic sensitisation
      and asthma.

PMID- 20816549
TI  - Role of viral respiratory infections in asthma and asthma exacerbations.
AB  - Viral respiratory tract infections are common and usually selflimited illnesses.
      For patients at risk of asthma, or with existing asthma, viral respiratory tract
      infections can have a profound effect on the expression of disease or loss of
      control. New evidence has shown that wheezing episodes early in life due to human
      rhinoviruses are a major risk factor for the later diagnosis of asthma at age 6
      years. For those with existing asthma, exacerbations are a major cause of
      morbidity, can need acute care, and can, albeit rarely, result in death. Viral
      respiratory tract infections, predominantly those caused by human rhinoviruses,
      are associated with asthma exacerbations. There is also evidence that
      deficiencies in antiviral activity and the integrity of the airway epithelial
      barrier could make individuals with asthma more likely to have severe viral
      respiratory infections of the lower airway, and thus increase the risk of
      exacerbation. In view of the effect of respiratory viruses on many aspects of
      asthma, efforts to understand the mechanisms and risk factors by which these
      airway infections cause changes in airway pathophysiology are a first step
      towards improved treatment.

PMID- 20816548
TI  - Management of severe asthma in children.
AB  - Children who are referred to specialist care with asthma that does not respond to
      treatment (problematic severe asthma) are a heterogeneous group, with substantial
      morbidity. The evidence base for management is sparse, and is mostly based on
      data from studies in children with mild and moderate asthma and on extrapolation
      of data from studies in adults with severe asthma. In many children with severe
      asthma, the diagnosis is wrong or adherence to treatment is poor. The first step
      is a detailed diagnostic assessment to exclude an alternative diagnosis ("not
      asthma at all"), followed by a multidisciplinary approach to exclude
      comorbidities ("asthma plus") and to assess whether the child has difficult
      asthma (improves when the basic management needs, such as adherence and inhaler
      technique, are corrected) or true, therapy-resistant asthma (still symptomatic
      even when the basic management needs are resolved). In particular, environmental
      causes of secondary steroid resistance should be identified. An individualised
      treatment plan should be devised depending on the clinical and pathophysiological
      characterisation. Licensed therapeutic approaches include high-dose inhaled
      steroids, the Symbicort maintenance and reliever (SMART) regimen (with budesonide
      and formoterol fumarate), and anti-IgE therapy. Unlicensed treatments include
      methotrexate, azathioprine, ciclosporin, and subcutaneous terbutaline infusions.
      Paediatric data are needed on cytokine-specific monoclonal antibody therapies and
      bronchial thermoplasty. However, despite the interest in innovative approaches,
      getting the basics right in children with apparently severe asthma will remain
      the foundation of management for the foreseeable future.

PMID- 20816551
TI  - Dangers in the garden.

PMID- 20816552
TI  - Environmental disasters and children.

PMID- 20816553
TI  - Parental handling of fear in children with cancer; caring in the best interests
      of the child.
AB  - The aim of this study was to gain a deeper understanding of how parents of
      children with cancer handle the fear in their children. Fifteen parents of 11
      children participated in focus-group interviews. Data were analyzed by a
      phenomenological hermeneutical method. The results suggest that the parents'
      handling was equivalent with caring in the best interests of the child. This
      included striving for the security and well-being of the child up to a certain
      point where the parents instead used their authority to maintain the child's
      physical health rather than trying to prevent or relieve the child's fear.

PMID- 20816554
TI  - "And then you'll see her in the grocery store": the working relationships of
      public health nurses and high-priority families in northern Canadian communities.
AB  - The aim of the study is to examine and articulate the nature of working
      relationships of public health nurses and high-priority families in small
      communities in northern Canada. Public health nurses working in northern, rural,
      and remote communities face unique and varied challenges. Reportedly, the hardest
      part of their job is working with families who have been deemed high priority or
      high risk. Working with these families in these contexts relies on relationships
      of reciprocity, trust, and communication. This qualitative research was guided by
      an interpretive hermeneutic inquiry; 32 families, 25 public health nurses, and
      three lay home visitors were interviewed from July 2005 through July 2006.
      Analysis was completed individually and through teamwork of the researchers.
      Findings suggest that the working relationship of public health nurses and high
      priority families in northern communities is complex and multifaceted. Nurses
      carefully negotiate the process of engaging and entering relationships,
      maintaining the relationships, and negotiating boundaries. The analysis offers
      insight into the everyday practices and problems that public health nurses and
      families encounter in providing care to a vulnerable, isolated, and often
      marginalized population while navigating the complexity of living and working in
      the same small communities.

PMID- 20816555
TI  - Family-centered pediatric nursing care: state of the science.
AB  - The purposes of this article were to summarize the development of family-centered
      pediatric care, review the current state of nursing research in this area, and
      recommend directions for future study. A literature review of 30 nursing research
      studies between 1995 and 2006 was conducted. Results revealed that evidence of
      consistent provision of family-centered pediatric care is lacking. Many areas of
      research remain undeveloped, but there is a solid foundation for moving forward
      in conducting research focused on assisting nurses in implementing this basic
      philosophy of practice in all settings and situations in which children receive
      health care.

PMID- 20816556
TI  - The effect of family routines on care for inner city children with asthma.
AB  - This article provides the results of a study utilizing baseline data from the
      School-Based Asthma Therapy Trial, an ongoing comprehensive school-based
      intervention for urban children. We examined the effect of family routines as
      measured by the Asthma Routines Questionnaire on asthma care measures of trigger
      control and medication adherence, as well as on parental quality of life. We
      found that families with more asthma routines had better adherence with
      preventive medications (r = .36) and less exposure to environmental triggers (r =
      -.22). These findings suggest that assisting families in developing routines
      around asthma care might improve preventive care for urban youth.

PMID- 20816557
TI  - Grandparent's health and functioning after a grandchild's death.
AB  - Approximately 160,000 grandparents experience the death of a grandchild each
      year; this represents a permanent, irrevocable loss for the grandparent,
      resulting in physical and emotional responses. Grandparents who lose a grandchild
      experience increased alcohol and drug use, thoughts of suicide, and pain for
      their adult child who is also grieving. Supportive resources available to
      grieving grandparents, the effects of the grandchild's death on the grandparent
      parent relationship, and the influence of race and ethnicity on grandparent
      grieving are discussed. Despite approximately 40,000 child and infant deaths each
      year, knowledge about grandparent health and functioning after the death of a
      grandchild is limited.

PMID- 20816558
TI  - Food security and dietary intake in midwest migrant farmworker children.
AB  - This article is a descriptive cross-sectional study with Latino migrant
      farmworker (MFW) families in Ohio. A demographic questionnaire, the U.S.
      Household Food Security Survey (USHFSS), and the Food Frequency Questionnaire
      were self-administered. Participants (N = 50) were primarily mothers of children
      with ages 2 to 13 years. USHFSS was 30% high, 18% marginal, 44% low, and 8% very
      low. Only 22% of the children met the minimum MyPyramid daily recommended food
      group servings for age and gender. Knowledge gained from these data will
      influence development of culturally appropriate nutrition interventions to help
      Latino MFW families achieve healthier nutrition and weight in their children.

PMID- 20816559
TI  - Content validation of the infant malnutrition and feeding checklist for
      congenital heart disease: a tool to identify risk of malnutrition and feeding
      difficulties in infants with congenital heart disease.
AB  - Infants with congenital heart disease (CHD) have a high prevalence of feeding
      difficulties and malnutrition. Early intervention decreases morbidity and long
      term developmental deficits. The purpose of this study was to develop and
      establish the content validity of a screening checklist to identify infants with
      CHD at risk of feeding difficulties or inadequate nutritional intake for timely
      referral to a feeding specialist or dietitian. The Delphi method was used, and
      expert participants reached consensus on 24 risk indicators. This study is the
      first step in establishing the validity and reliability of a screening tool for
      early intervention of feeding difficulties and inadequate nutritional intake in
      infants with CHD.

PMID- 20816560
TI  - Response to H1N1 influenza outbreak in a pediatric children's hospital:
      challenges faced and lessons learned.
AB  - In April 2009, media reports indicated an outbreak of swine flu (H1N1) resulting
      from several students from a local high school having been in Mexico. Over the
      next 6 weeks, the demand for the services of the children's hospital strained
      available resources, requiring innovative measures to care for more than 3,200
      pediatric patients and their families with influenza-like illness. The purpose of
      this analysis is to provide an overview of the established emergency response to
      disasters for hospitals, describe the chronology of events of this disaster and
      the planning improvisations needed for management, and discuss the lessons
      learned and challenges for the future.

PMID- 20816561
TI  - Adolescents as health agents and consumers: results of a pilot study of the
      health and health-related behaviors of adolescents living in a high-poverty urban
      neighborhood.
AB  - Although there is a considerable literature on how adolescents make decisions
      which lead to risky behaviors (e.g., unprotected sex, drug use) and adversely
      affect the health and well-being of youth, little is known about the routine
      behaviors youth engage in which influence their health (e.g., having permanent
      teeth extracted, discontinuing antibiotics prematurely, delaying or going without
      treatment of subacute illnesses and minor injuries) and concomitantly the factors
      which influence these behaviors. In an effort to begin to fill this gap, we have
      undertaken a study of routine health behaviors and the factors which bear on them
      in adolescents from a high-poverty urban neighborhood. In this article, we
      present the results of the pilot phase of the study in which we documented the
      behavior of 10 adolescents from Camden, New Jersey, the fifth poorest city in the
      United States, and explored with them their perceptions of the decisions they
      made and the factors that gave rise to them. We found that participants had an
      insufficient understanding of their health problems and consequences of their
      health actions, problems in understanding and being understood by health care
      professionals, and reluctance to involve parents in routine health care
      decisions. The implications of these findings are discussed in relation to
      improving the health of vulnerable youth.

PMID- 20816562
TI  - Association of changes in self-efficacy, voluntary physical activity, and risk
      factors for type 2 diabetes in a behavioral treatment for obese preadolescents: a
      pilot study.
AB  - Childhood obesity is increasing in the United States; thus, physicians, nurses,
      and other health care professionals seek to refer patients to interventions that
      will reliably improve physical activity and nutrition behaviors. The present 12
      week, two-session-per-week protocol, based on social cognitive theory, was given
      preliminary testing with 23 obese children (M(age) = 11.7 years) with risk
      factors for Type 2 diabetes. A significant within-group improvement in number of
      days per week of 60 or more minutes of voluntary physical activity was reported.
      Changes in measures of both task self-efficacy (beta = .39) and self-regulatory
      efficacy (beta = .44) significantly contributed to the significant portion of the
      variance explained in change in voluntary physical activity (R(2) = .40).
      Significant improvements in total cholesterol and body mass index (kg/m(2)) were
      also found. Correlations between changes in physical activity and changes in each
      physiological factor tested were each in the expected direction but did not reach
      statistical significance. Results suggest that replications and extensions of
      this pilot study, with greater experimental power, are warranted.

PMID- 20816563
TI  - Bisphenol a exposure: human risk and health policy.
AB  - Bisphenol A (BPA) is a chemical used extensively to manufacture commonly used
      plastics and epoxy resin liners for food and beverage cans. BPA, with properties
      similar to diethylstilbestrol, has been shown to exert endocrine-disrupting
      effects and result in behavioral changes, altered growth, and early secondary
      sexual maturation. In 2008, legislation was introduced at the state and federal
      level to ban the use of BPA in children's products. The purpose of this article
      is to provide the reader with the weight of evidence, current federal regulatory
      stance, and proposed legislation regarding the safe use of BPA.

PMID- 20816564
TI  - Nurse researchers in children's hospitals.
AB  - Little is known about the role of nurse researchers (NRs) and the structure of
      nursing research programs in children's hospitals in the United States. This
      descriptive study obtained survey data from 33 NRs. Data suggest that the NR role
      is emerging and has both commonalities and unique components when compared with
      the previous studies of NRs in adult hospitals. Most participants have been in
      their position for less than 4 years. Conducting research, having staff
      development related to research, and facilitating evidence-based practice or
      research were common responsibilities. The structure of nursing research programs
      impacts both the NRs and the program outcomes.

PMID- 20816565
TI  - African American parents'/guardians' health literacy and self-efficacy and their
      child's level of asthma control.
AB  - Nearly 1 of 10 American children has asthma. Asthma is addressed in Healthy
      People 2010 as a public health problem. This study examined the relationship
      between parents'/guardians' health literacy levels and their perceived self
      efficacy to manage their child's asthma. A four-page asthma questionnaire was
      developed to assess the self-efficacy of parents/guardians of African American
      children with asthma. There was a statistically significant relationship among
      the parents'/guardians health literacy levels and their perceived efficacy
      expectations to manage their child's asthma. There is evidence that high
      parental/guardian self-efficacy and successful asthma management contribute to a
      child with well-controlled asthma. It is necessary for patient educators to
      capitalize on physician/nurse visits and use the time for asthma education,
      particularly to increase the efficacy expectations of parents/guardians with
      limited health literacy skills.

PMID- 20816566
TI  - Siblings' perceptions of the costs and rewards of diabetes and its treatment.
AB  - This qualitative descriptive study explored the perceptions of siblings about the
      costs and rewards of diabetes and its management for the child with Type 1
      diabetes, the sibling, and the family. Twenty children were interviewed using a
      semistructured interview guide. Children attending a day camp for children with
      diabetes and their siblings made up the sample. Iterative and thematic analysis
      yielded three cost themes and two reward themes. The perspectives of siblings
      about diabetes may aid in the development of family-focused teaching programs
      with the goal to assist family adaptation to Type 1 diabetes.

PMID- 20816567
TI  - Improved nurse readiness through pediatric mock code training.

PMID- 20816568
TI  - A reevaluation of the 2000 Surgeon General's report on America's oral health:
      opportunities for health care providers.

PMID- 20816569
TI  - Technological advances in genetic testing.

PMID- 20816570
TI  - Research commentary--the integral role of families.

PMID- 20816571
TI  - Propofol.
AB  - Therapeutic Reviews aim to provide essential independent information for health
      professionals about drugs used in palliative and hospice care. The content is
      also available on www.palliativedrugs.com and will feature in future editions of
      the Hospice and Palliative Care Formulary USA and its British and Canadian
      counterparts. The series editors welcome feedback on the articles
      (hq@palliativedrugs.com).

PMID- 20816573
TI  - Genetic predisposition to cancer. Preface.

PMID- 20816574
TI  - Inherited predisposition to cancer: introduction and overview.
AB  - The past three decades have witnessed an explosion in information regarding the
      genetic mutations underlying predisposition to common malignancies. Discoveries
      are now being made regarding genomic variants associated with disease risk for,
      and outcome following, treatment for cancer. Responsible translation of these
      discoveries to medical practice requires attention to principles of clinical
      utility as well as social and ethical aspects.

PMID- 20816575
TI  - Breast cancer predisposition syndromes.
AB  - A small, but important, percentage of breast cancer cases is caused by the
      inheritance of a single copy of a mutated gene. BRCA1 and BRCA2 are the genes
      most commonly associated with inherited breast cancer; however, mutations in TP53
      and PTEN cause Li-Fraumeni syndrome and Cowden syndrome, respectively, both of
      which are associated with high lifetime risks of breast cancer. Advances in the
      field of breast cancer genetics have led to an improved understanding of
      detection and prevention strategies. More recently, strategies to target the
      underlying genetic defects in BRCA1- and BRCA2-associated breast and ovarian
      cancers are emerging and may have implications for certain types of sporadic
      breast cancer.

PMID- 20816576
TI  - Upper gastrointestinal cancer predisposition syndromes.
AB  - Malignancies of the upper gastrointestinal tract form a heterogeneous group of
      cancers characterized by unique epidemiology and biology. Despite these
      differences, survival for advanced disease remains poor across the panel of
      diseases, from cancers of the esophagus, stomach, pancreas, and, until recently,
      even gastrointestinal stromal tumors. Genetic predisposition syndromes associated
      with these diseases comprise an emerging subset of these diseases that may
      provide valuable information on cause and etiology. They may provide insight into
      molecular drivers for the disease, or disease subtypes, and also insights into
      novel gene/environment interactions. This review summarizes the current
      understanding of genetic predisposition syndromes of cancers of the upper
      gastrointestinal tract.

PMID- 20816577
TI  - Clinical genetics of hereditary colorectal cancer.
AB  - Colorectal cancer (CRC) is a common disease, and approximately 25% of patients
      have a familial component. High-penetrance singlegene germline mutations
      conferring a true hereditary susceptibility account for around 5% to 6% of all
      cases. Lynch syndrome is the most common hereditary form of colorectal cancer.
      Much of the hereditary component in the remaining familial cases of CRC is likely
      polygenic, and many of the genetic changes involved are as yet unidentified. This
      article addresses the most clinically important CRC genetic syndromes.

PMID- 20816578
TI  - Genitourinary cancer predisposition syndromes.
AB  - Despite epidemiologic data supporting a significant genetic contribution to the
      cause of genitourinary malignancies, their diagnosis rarely results in clinical
      genetics referral and the heritability of prostate, bladder, kidney, and
      testicular cancer remains poorly understood. Little of this inheritance has been
      explained by rare, high-penetrance predisposition syndromes and, although rare
      genetic variation may explain some of the remaining familial predisposition,
      recent genome-wide association studies support an important causal role for more
      common genomic variation and other structural variants. Susceptibility loci
      associated with risk of prostate, bladder, and testicular cancer have been
      identified that may improve our understanding of the cause and natural history of
      these malignancies. It remains to be seen whether this emerging knowledge of
      genetic predisposition can meaningfully contribute to the clinical management of
      genitourinary malignancies.

PMID- 20816580
TI  - Endocrine cancer predisposition syndromes: hereditary paraganglioma, multiple
      endocrine neoplasia type 1, multiple endocrine neoplasia type 2, and hereditary
      thyroid cancer.
AB  - The hereditary paraganglioma, MEN1, MEN2, and hereditary thyroid cancer syndromes
      are clinically discernable and genetically distinct. The first 3 syndromes have
      been well characterized in the past 10 to 15 years. Recognizing these 3 syndromes
      and using a multidisciplinary team approach creates valuable opportunities for
      early diagnosis, reduction of morbidity and mortality, and avoidance of surgical
      misadventures. Hereditary paraganglioma has parent-of-origin effects and gene
      environment interactions that indicate its evolution, and the syndrome sheds
      light on the role of mitochondria and energy metabolism in cancer. This article
      delineates the clinical presentation and practical management issues and
      summarizes the history, gene discovery, and molecular insights for each syndrome.

PMID- 20816581
TI  - Heritability of hematologic malignancies: from pedigrees to genomics.
AB  - Many hematologic malignancies have an underlying heritable component. Although
      not as well characterized as the acquired genetic abnormalities that define
      important prognostic and therapeutic subgroups of myeloid and lymphoid neoplasms,
      investigations are beginning to unravel the role of germline genetic variation in
      the predisposition to hematologic malignancies. Information gained from the study
      of striking family pedigrees, epidemiologic data, and candidate genes are now
      being combined with unbiased genome-wide investigations to outline the network of
      genetic abnormalities that contribute to hematologic malignancy risk. This
      article reviews the current understanding of the heritability of hematologic
      malignancies in the genomics era.

PMID- 20816579
TI  - Hereditary genodermatoses with cancer predisposition.
AB  - In this article hereditary genodermatoses with cancer predisposition are
      reviewed, including nevoid basal cell carcinoma syndrome, neurofibromatosis types
      1 and 2, tuberous sclerosis complex, xeroderma pigmentosum, and dyskeratosis
      congenita. Hereditary melanoma is also included, though it differs from the
      others in several respects. The underlying genetic aberrations causing these
      syndromes are largely known, allowing novel treatments to be developed for some
      of these disorders. Early recognition and diagnosis allows for close follow-up
      and surveillance for associated malignancies.

PMID- 20816582
TI  - Genome-wide association studies of cancer predisposition.
AB  - Genome-wide association studies (GWAS) have now been performed in nearly all
      common malignancies and have identified more than 100 common genetic risk
      variants that confer a modest increased risk of cancer. For most discovered
      germline risk variants, the per allele effect size is small (<1.5) and the
      biologic mechanism of the detected association remains unexplained. Exceptions
      are the risk variants identified in JAK2 in myeloproliferative neoplasm and in
      the KITLG gene in testicular cancer, which are each associated with nearly a 3
      fold increased risk of disease. GWAS have provided an efficient approach to
      identifying common, low-penetrance risk variants, and have implicated several
      novel cancer susceptibility loci. However, the identified low-penetrance risk
      variants explain only a small fraction of the heritability of cancer and the
      clinical usefulness of using these variants for cancer-risk prediction is to date
      limited. Studies involving more heterogeneous populations, determination of the
      causal variants, and functional studies are now necessary to further elucidate
      the potential biologic and clinical significance of the observed associations.

PMID- 20816583
TI  - Treatment of Helicobacter pylori infection: the past and the future.

PMID- 20816584
TI  - Ventilator-associated pneumonia: a review.
AB  - Ventilator-associated pneumonia (VAP) is the most frequent intensive-care-unit
      (ICU)-acquired infection, with an incidence ranging from 6 to 52% [1,2,3,4].
      Several studies have shown that critically ill patients are at high risk for
      getting such nosocomial infections [3,4]. VAP continues to be a major cause of
      morbidity, mortality and increased financial burden in ICUs [5,6,7,8]. Over the
      years there has been a significant advance in our understanding of ventilator
      associated pneumonia. This article reviews the various aspects of VAP such as
      definition, risk factors, etiological agents, diagnosis, treatment and prevention
      with emphasis on the recent advances.

PMID- 20816585
TI  - Polycystic ovary syndrome and autoimmunity.
AB  - Polycystic ovary syndrome (PCOS) is characterized by laboratory and/or clinical
      features consisting of hyperandrogenism with chronic anovulation and is currently
      one of the most common endocrinopathies in women of fertile age. PCOS is
      associated with a variety of endocrine and metabolic disturbances. It was
      demonstrated that the prevalence of autoimmune thyroiditis is high among these
      patients. Recent studies reveal a higher incidence of autoantibodies such as anti
      histone, anti-dsDNA presented in systemic autoimmune disease, however their
      clinical significance is still unknown. According to results of current research
      the syndrome could be possibly associated with some autoimmune diseases. Further
      studies are required to determine the role of organ-specific and non-specific
      autoantibodies in patients with PCOS.

PMID- 20816586
TI  - Reversible and non-reversible cardiovascular risk in patients treated with lipid
      lowering therapy: analysis of SEAS and JUPITER trials.
AB  - A number of clinical trials have confirmed that statin treatment and, more
      generally, LDL-lowering treatment, are able to reduce CHD and CVD events in a
      wide range of clinical conditions associated with increased cardiovascular risk.
      However, the most recent trials have also identified patient groups in which
      lipid-lowering treatment shows a more limited preventive potential due to the
      "non-reversibility" of part of the cardiovascular risk, which dilutes the
      observed treatment effect by events that are not directly a consequence of
      atherosclerosis. The use of lipid-lowering therapy in these patients should be
      driven not only by their absolute risk, as suggested by the most recent American
      and European guidelines, but also by their overall clinical setting and by the
      evidence of benefit obtained in controlled trials in comparable populations.

PMID- 20816587
TI  - Why management and leadership education for internists?
AB  - Around the world, there is an increasing need for more efficiency in healthcare
      alongside cost containment. Internal medicine physicians are in a pivotal
      position in this regard. In many countries, they act as bridges between
      ambulatory/continuity of care systems and hospital-based intensive care and
      sophisticated therapies. Within the medical field, they often bridge gaps between
      many specialities increasingly required to provide modern medical care. These
      skills of managing complex environments, being sensitive to health economics and
      using large amounts of information, are not normally taught or developed in
      programmes of internal medicine. While some skills are natural and acquired
      through practice, other skills would benefit from insights from the fields of
      management. On the other hand, it seems critical to have internists playing a
      leading role in the future care of aging populations, and they are the most
      likely to understand the needs of these multi-pathology cases. On a practical
      level, internists face the daily challenges of engaging and leading as many
      people as possible to provide the best care; this requires very good leadership,
      negotiation, team-working and change-management skills, all of which can be
      vastly enhanced with specific education initiatives that are targeted and
      customised to physicians' needs. Management education for internists should be
      "spiral", starting from medical school and expanding to incorporate issues as the
      physician matures into new activities and responsibilities. In practical terms,
      current internists and residents of internal medicine can be brought into contact
      with such education by a combination of workshops as well as residential and
      online courses.

PMID- 20816589
TI  - The diagnostic value of video capsule endoscopy.
AB  - BACKGROUND AND AIMS: Video capsule endoscopy (VCE) offers the best means of
      studying small bowel, but is expensive. We investigated how physicians appraise
      the value of VCE. METHODS: A questionnaire was sent to remitting physicians
      comprising questions on the value of VCE in altogether 189 adults. The follow-up
      time was at least one year. The patient history was also scrutinized in case
      records. RESULTS: The most common indications for VCE were anaemia (n=100) or
      gastrointestinal bleeding (n=21) (60%), suspicion of Crohn's disease (21%),
      abdominal pain (9%) and coeliac disease (6%). The diagnostic value of VCE was
      rated best in patients suffering from anaemia or bleeding, being decisive or
      beneficial in 33% (OR 2.3, CI=1.1-4.8 compared to all series) and helpful in
      exclusion in an additional 36%. In Crohn's disease, VCE was helpful in the
      exclusion of intestinal lesions in 50% of cases; in coeliac disease the
      corresponding percentage was 42%. When abdominal pain was the only indication for
      VCE, the examination was beneficial in one patient only. CONCLUSIONS: The
      diagnostic value of VCE was evident in patients with anaemia or gastrointestinal
      bleeding. The procedure was deemed to be helpful in exclusion also in Crohn's
      disease and in coeliac disease. Abdominal pain was a rare indication, and the
      diagnostic yield limited.

PMID- 20816588
TI  - Clinical characteristics and outcome of inpatients versus outpatients with venous
      thromboembolism: findings from the RIETE Registry.
AB  - BACKGROUND: Patients with venous thromboembolism (VTE) treated with
      anticoagulants are at risk of death from pulmonary embolism (PE) and/or bleeding.
      However, whether patients who develop VTE in hospital have a higher complication
      rate than those who develop VTE in an outpatient setting is unclear. PATIENTS AND
      METHODS: RIETE is an ongoing, prospective registry of consecutive patients with
      acute, objectively confirmed, symptomatic VTE. We compared the 3-month incidence
      of fatal PE and fatal bleeding in patients in whom the VTE had developed while in
      hospital for another medical condition (inpatients) with those who presented to
      the emergency ward because of VTE (outpatients). RESULTS: Up to April 2008,
      22,133 patients with acute VTE were enrolled: 10,461 (47%) presented with PE,
      11,672 with deep vein thrombosis. Overall, 6445 (29%) were inpatients. During the
      study period, those who developed VTE as inpatients had a significantly higher
      incidence of fatal PE (2.1% vs. 1.5%; odds ratio: 1.4; 95% CI: 1.1-1.7), overall
      death (7.0% vs. 5.4%; odds ratio: 1.3; 95% CI: 1.2-1.5), and major bleeding (2.9%
      vs. 2.1%; odds ratio: 1.4; 95% CI: 1.1-1.6) than outpatients. The incidence of
      fatal bleeding was not significantly increased (0.7% vs. 0.5%; odds ratio: 1.2;
      95% CI: 0.9-1.8). In multivariable analysis, inpatient status was significantly
      associated with a higher risk for fatal PE (odds ratio: 1.3; 95% CI: 1.1-1.7).
      CONCLUSIONS: VTE occurring in hospitalized patients carries a significantly
      higher risk for death of PE than in outpatients, underscoring the importance of
      VTE prevention strategies in the hospital setting.

PMID- 20816590
TI  - Stress-related mucosal disease: incidence of bleeding and the role of omeprazole
      in its prophylaxis.
AB  - BACKGROUND: Upper gastrointestinal bleeding is the severe complication of stress
      related mucosal disease in hospitalized patients. In intensive care units (ICU),
      risk factors are well defined and only mechanical ventilation and coagulopathy
      proved to be relevant for significant bleeding. On the contrary, in non-ICU
      settings there is no consensus about this issue. Nevertheless, omeprazole is
      still widely used in prophylaxis of bleeding. The objective of our study was to
      evaluate the relevance of stress-related mucosal disease bleeding in patients
      admitted to an internal medicine ward, and the role of omeprazole in its
      prophylaxis. METHODS: We conducted a retrospective study in which we analysed
      consecutive patients who were admitted to our ward over a year. We recorded
      demographic characteristics of the patients, potential risk factors for stress
      related mucosal disease (clinical data, laboratory, and medication),
      administration of prophylactic omeprazole, and total cost of this prophylaxis.
      Patients with active gastrointestinal bleeding on the admission were excluded. We
      recorded every upper gastrointestinal bleeding event with clinical relevance.
      RESULTS: Five hundred and thirty-five patients, mean age 70 years, mean length of
      stay 9.6+/-7.7 days; 140 (26.2%) patients were treated with 40 mg of omeprazole
      intravenously, 193 (36.1%) with 20mg of omeprazole orally, and 202 (37.8%)
      patients had no prophylaxis. There was only one episode (0.2%) of clinically
      relevant bleeding. CONCLUSION: In patients admitted to an internal medicine ward,
      incidence of upper gastrointestinal bleeding as a complication of stress-related
      mucosal disease is low. We found that there is no advantage in prophylaxis with
      omeprazole.

PMID- 20816591
TI  - The prevalence of celiac disease in patients fulfilling Rome III criteria for
      irritable bowel syndrome.
AB  - BACKGROUND AND AIMS: Celiac disease shares several symptoms which constitute some
      of the ROME criteria used for the diagnosis of irritable bowel syndrome (IBS),
      and as such many patients with underlying Celiac disease may be mistakenly
      diagnosed as having IBS. The aim of the present study was to determine the
      prevalence of Celiac disease in patients with IBS fulfilling ROME III criteria.
      MATERIALS AND METHODS: Patients who fulfilled ROME III criteria for irritable
      bowel syndrome were screened for Celiac disease using the Biocard(TM) Celiac
      Disease Stick test, and patients who tested positive had their serum samples
      analyzed for antigliadin IgA and IgG, and anti-tissue transglutaminase IgA
      antibodies. Patients with detectable antibody levels underwent endoscopic
      duodenal biopsy to confirm a diagnosis of Celiac disease. RESULTS: Two of 100
      patients who were diagnosed as having irritable bowel syndrome as per the Roma
      III criteria were found to have elevated levels of serum antigliadin IgA and IgG,
      and anti-tissue transglutaminase IgA antibodies, with histological evidence of
      Celiac disease on examination of duodenal biopsy. Both patients were started on a
      gluten-free diet, showing significant improvement in their symptoms on follow-up.
      CONCLUSIONS: Celiac disease is a common finding among patients labeled as IBS.
      Celiac disease must be considered in differential diagnosis of IBS especially in
      the therapy refractory group.

PMID- 20816592
TI  - Percutaneous treatment for symptomatic pancreatic pseudocysts: Long-term results
      in a single center.
AB  - PURPOSE: The aim of the study was to present and evaluate the long-term results
      of percutaneous catheter drainage (PCD) in the treatment of symptomatic
      pancreatic pseudocysts (PPC). METHODS: We performed a retrospective analysis of
      128 patients with 140 PPC treated by PCD from 01/01/1989 to 12/31/2008. All
      procedures were performed under ultrasound control. Surgical treatment was
      planned only in patients with failed PCD. The patients were followed up monthly
      with sonography for 12 months. The primary outcome was conversion rate to
      surgery. Secondary outcomes were disappearance of PPC, requirement for additional
      treatment, length of hospital stay, and catheter dwell time. RESULTS: During the
      follow-up, 42 of the 140 cysts (30%) recurred. 19/42 cysts were small and they
      were followed up without intervention and 23/42 cysts required further
      intervention. These patients were offered a second attempt but 5 patients
      declined it and they chose to undergo surgery. The remaining 18 patients
      underwent second PCD and 10 of them developed recurrence. All of them underwent
      third PCD and 6 of the 10 patients developed recurrences. Four and 2 of them
      necessitated surgery and follow-up, respectively. In total, 9 of the 128 patients
      (7%) underwent surgery during the study period. Medians (interquartile ranges) of
      hospital stay and catheter dwell time were 19 (14-23) and 23 (15-43) days,
      respectively. There were no complications related to the procedure. CONCLUSION:
      PCD is a safe and effective management for PPC, with low recurrence rates and
      complication rate and it can eliminate the need for surgery in majority of
      patients with PPC.

PMID- 20816593
TI  - The addition of pioglitazone in type 2 diabetics poorly controlled on insulin
      therapy: a meta-analysis.
AB  - AIM: To quantify the effect of a pioglitazone on glycemic control and lipid
      parameters, as well as the risk of adverse events when incorporated into the
      treatment regimen of patients with type 2 diabetes inadequately controlled on
      insulin. METHODS: The electronic databases PubMed, Embase and The Cochrane
      Library were searched systematically to identify randomized controlled trials
      (RCTs) of pioglitazone therapy in patients with type 2 diabetes mellitus (DM)
      inadequately controlled after treatment with insulin. Data on change of
      haemoglobin A1C (HbA1c), fasting plasma glucose (FPG), lipid parameters and risk
      of hypoglycemic, edema events were extracted from each study and pooled according
      to fixed effect model or random effect model in meta-analyses. RESULTS: Four RCTs
      including 1767 patients were included. The pooled estimate of change in HbA1c
      from baseline was 1.22% (95% CI 1.01-1.44, p<0.001 vs. baseline) and of change in
      FPG from baseline was 1.63 mmol/l (95% CI 0.75-2.50, p<0.001 vs. baseline).
      Pioglitazone significantly increased high-density lipoprotein cholesterol (HDL-c)
      level (0.2 mmol/L, 95%CI: 0.13-0.28) and low-density lipoprotein cholesterol (LDL
      c) level (0.10 mol/L, 95%CI: 0.09-0.17), and lowered triglyceride (TG) level
      (0.05 mmol/L, 95%CI: 0.01-0.09). The odds of experiencing a hypoglycemic event in
      pioglitazone-treated arms was significantly higher than comparator treatments
      (RR=1.57, 95% CI 1.12-2.20, p<0.001). The case was the same with edema (RR=2.42,
      95% CI 1.67-3.50, p<0.001). CONCLUSIONS: Our study implied that in patients with
      type 2 DM whose control is inadequate on insulin therapy, the additional
      pioglitazone could significantly improve glucose metabolism and might have a
      positive effect on important components of the lipid profile, which may have
      important implications in reducing the risk of cardiovascular disease, a major
      long-term complication in type 2 diabetes mellitus. Besides, the adverse events
      (AEs) were well tolerated.

PMID- 20816594
TI  - Impact of exercise intensity and duration on insulin sensitivity in women with
      T2D.
AB  - BACKGROUND: Clinical guidelines seldom provide in depth information about the
      most suitable type and intensity of exercise to obtain optimal benefit in
      different subgroups of T2D individuals. The aim of this study was to examine the
      effect of group exercise training on exercise capacity, insulin sensitivity and
      HbA1c in women with diabetes. METHODS: Twenty-two women with T2D participated in
      a supervised group exercise program for six months. The program combined
      endurance and resistance exercise. The duration and intensity of exercise for
      each subject was recorded. The volume of exercise was calculated as the product
      of exercise duration and intensity. Exercise capacity, insulin sensitivity and
      HbA1c were measured at baseline and after six months of training. The subjects
      were dichotomized with respect to training volume in a high training volume group
      and a low training volume group. RESULTS: Exercise capacity did not change
      significantly during the training period. Insulin sensitivity increased
      significantly and HbA1c decreased significantly from baseline in the high volume
      group but not in the low volume group. The increase in insulin sensitivity was
      explained with the intensity of exercise by 30%. The reduction in HbA1c was
      explained with exercise by 25%. CONCLUSION: Improvement in insulin sensitivity
      after six months combined supervised group training in female diabetic subjects
      is related to exercise intensity, whereas the reduction in HbA1c is related
      mainly to training volume. Metabolic effects of training may be seen in the
      absence of improved exercise capacity.

PMID- 20816595
TI  - Predictors of insulin resistance in the obese with metabolic syndrome.
AB  - BACKGROUND: In the obese, the metabolic syndrome (MetS) is assumed to reflect
      insulin resistance. OBJECTIVE: To determine the predictors of insulin resistance
      in obese subjects with MetS. DESIGN: We used the 90th percentile of the
      homeostasis model assessment (HOMA) to define insulin resistance in 4958
      nondiabetic adults evaluated in the National Health and Nutrition Examination
      Surveys, 1999-2004, and compared the 373 obese subjects who were insulin
      resistant (HOMA 9.52+/-5.73) to a control group of 373 obese who had the highest
      sensitivity to insulin (HOMA 1.79+/-0.44). MEASUREMENTS: MetS was present in 312
      (83.6%) obese with insulin resistance and in 156 (41.8%) obese from the insulin
      sensitive control group. Demographic, metabolic, and lifestyle variables were
      analyzed with logistic regression. RESULTS: In a logistic model of insulin
      resistance given the presence of MetS, the significant predictors were
      triglycerides (P=0.0021), body mass index (P=0.0096), HDL-cholesterol (P=0.0098),
      age (P=0.0242) and smoking (P=0.0366). LIMITATIONS: Cross-sectional design
      prevents elucidation of causality for the association between insulin resistance
      and MetS. CONCLUSIONS: Insulin resistance is not an obligatory correlate of MetS
      in the obese. Its likelihood can be predicted by cigarette smoking and by the
      severity of obesity and dyslipidemia.

PMID- 20816596
TI  - Renin angiotensin system polymorphisms in patients with metabolic syndrome
      (MetS).
AB  - BACKGROUND: The genes associated with hypertension could be genetic risk factors
      for metabolic syndrome (MetS). AIM: To determine the frequency of M235T and T174M
      AGT, I/D-ACE and A1166C-AGTR1 in hypertensive patients with MetS and to evaluate
      the relationship between these polymorphisms and central obesity and
      dyslipidemia, respectively. MATERIALS AND METHODS: We performed AGT, AGTR1 and
      ACE genotyping in 56 hypertensive women (24 with MetS) and 71 normotensive women
      using PCR-RFLP methods and PCR, respectively. RESULTS: Hypertensive patients
      carrying the mutated TT235, MM174 and DD genotypes had an 1.53 (p=0.56), 1.78
      (p=0.52) and 1.28 (p=0.78)-fold increased risk to develop MetS. Hypertensive
      carriers of both mutated TT235 and MM174 or TT235 and D/D or TT235 and CC+AC
      genotypes had an 8.15 (p=0.04), 4.83 (p=0.04) and 10.53 (p=0.05)-fold increased
      risk to develop MetS. Hypertensive patients with MetS and TT, D/D or CC genotypes
      had higher body mass index compared to hypertensive patients without MetS
      (p</=0.05 for all the genotypes). Hypertensive patients with MetS and TT235,
      MM174, D/D or CC1166 genotypes had higher triglyceride levels, lower HDL
      cholesterol levels and higher waist circumference compared to hypertensive
      patients without MetS (p</=0.05, except for the association between CC1166 and
      HDL-cholesterol level). CONCLUSIONS: The effect of the T174M, I/D and A1166C
      polymorphisms on MetS may depend on the M235T polymorphism. Among hypertensive
      subjects with MetS, the presence of TT235, MM174, DD and CC1166 genotypes could
      be a risk factor for central obesity and dyslipidemia.

PMID- 20816598
TI  - Prevalence of renal artery stenosis in flash pulmonary oedema: determination
      using gadolinium-enhanced MRA.
AB  - PURPOSE: The primary purpose was to determine the prevalence of renal artery
      stenosis (RAS) in patients presenting with acute ("flash") pulmonary oedema
      (FPE), without identifiable cause using contrast-enhanced magnetic resonance
      angiography (CE-MRA) of renal arteries. A secondary goal was to correlate
      clinical parameters at presentation with the presence or absence of RAS.
      MATERIALS AND METHODS: Patients presenting with acute pulmonary oedema without
      identifiable cause prospectively underwent CE-MRA. >50% renal artery stenosis was
      considered significant. Clinical parameters (blood pressure, serum creatinine,
      history of hypertension/hyperlipidaemia) were compared in patients with and
      without RAS using an unpaired t-test. Results expressed; mean (+/-SD). RESULTS:
      20 patients (4 male, 16 female, age 78.5+/-11 years) underwent CE-MRA. 9 patients
      (45%) had significant RAS (6 (30%) bilateral, 3 (15%) unilateral). Systolic BP
      was higher in patients with RAS (192+/-38 mm Hg) than those without (134+/-30 mm
      Hg) (p<.005). Diastolic BP was higher in patients with RAS (102+/-23 mm Hg) than
      those without (76+/-17 mm Hg) (p<.01). All patients with RAS and 6/11(55%)
      patients without RAS had a history of hypertension. No significant difference in
      creatinine or hyperlipidaemia history was observed. CONCLUSION: The prevalence of
      RAS in patients presenting with FPE is 45%. The diagnosis should be considered in
      patients presenting with unexplained acute pulmonary oedema, particularly if
      hypertensive at presentation.

PMID- 20816597
TI  - Diagnostic performance of adenosine deaminase activity in pleural fluid: a single
      center experience with over 2100 consecutive patients.
AB  - OBJECTIVE: To determine the diagnostic utility of adenosine deaminase (ADA) in a
      large series of pleural effusions of different etiologies. METHODS: A
      retrospective study of 2104 consecutive patients presenting with pleural effusion
      was carried out at a Spanish university hospital. ADA levels in pleural fluid
      were determined using a non-Giusti automatic kinetic assay, and a receiver
      operating characteristics curve analysis was applied to estimate their
      discriminative properties. RESULTS: Pleural tuberculosis (TB) accounted for 221
      (10.5%) effusions. Pleural fluid ADA >35U/L yielded 93% sensitivity, 90%
      specificity, a positive likelihood ratio (LR) of 10.05 and a negative LR of 0.07
      for the diagnosis of TB among lymphocytic exudates. The ADA activity was
      significantly higher in neutrophil- (111.6U/L) than in lymphocyte-rich (62.4U/L;
      p=0.002) TB effusions. Overall, more than 40% of parapneumonics and half of
      lymphomatous effusions exceeded the cutoff set for TB. These were the only causes
      of ADA activity above 250U/L. When the prevalence of TB as a cause of exudative
      effusions is low (e.g., 1%), the estimated positive predictive value of the ADA
      test may be as low as 7%, although the negative predictive value remains high
      (99.9%). CONCLUSION: Where available, pleural ADA should be routinely used to
      rule TB in or out in areas with moderate to high or low TB prevalence,
      respectively. A high ADA level is a characteristic not only of lymphocytic, but
      also of neutrophilic TB effusions. An extremely high ADA activity should raise
      suspicion of empyema or lymphoma.

PMID- 20816599
TI  - Confusion, Urea, Respiratory Rate and Shock Index or Adjusted Shock Index (CURSI
      or CURASI) criteria predict mortality in community-acquired pneumonia.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is common and associated with a
      significant mortality. Shock index, heart rate divided by systolic blood
      pressure, has been shown to be associated with outcome in sepsis. OBJECTIVE: To
      examine the usefulness of two new criteria CURSI (confusion, urea, respiratory
      rate and shock index), and CURASI where shock index is replaced by temperature
      adjusted shock index in mortality assessment of CAP. METHODS: A prospective study
      was conducted in Norfolk and Suffolk, UK. We explored the usefulness of CURSI and
      CURASI which we derived and performed mapping exercise using a different cohort.
      In this study we compared these new indices with the CURB-65 criteria in
      correctly predicting mortality in CAP. RESULTS: A total of 190 patients were
      included (males=53%). The age range was 18-101 years (median=76 years). There
      were a total of 54 deaths during a six-week follow-up. All died within 30-days.
      Sixty-five (34%) had severe pneumonia by CURB-65. Using CURSI and CURASI, 71(37%)
      and 69(36%) had severe pneumonia, respectively. The sensitivity, specificity,
      positive and negative predictive values in predicting death during six-week
      follow-up were comparable among three indices examined. The Receiver Operating
      Characteristic curve values (95%CI) for the criteria were 0.67(0.60-0.75) for
      CURB-65, 0.67(0.59-0.74) for CURSI and 0.66(0.58-0.74) for CURASI (p>0.05). There
      were strong agreements between these three indices (Kappa values > or =0.75 for
      all). Repeating analyses in those who were aged 65years and over (n=135) did not
      alter the results. CONCLUSIONS: Both CURSI and CURASI are similarly useful to
      CURB-65 in predicting deaths associated with CAP including older patients.

PMID- 20816600
TI  - Evaluation of a direct test for seasonal influenza in outpatients.
AB  - OBJECTIVE: To present our experience regarding the use of a rapid diagnostic test
      for seasonal influenza A and B. METHODS: We systematically collected and analyzed
      our data regarding the use of a rapid diagnostic test for seasonal influenza A
      and B in patients with specific respiratory symptoms that sought medical
      services, during the time period from 01/01/2009 to 30/05/2009, from a network of
      physicians (SOS Doctors) who perform house-call visits in the area of Attica,
      Greece. RESULTS: From the total of 16,335 house-call visits performed during the
      evaluated period, 3412 (20.8%) were due to respiratory/influenza symptoms; 197
      (5.8%) patients were tested for influenza. From the 184 patients with available
      data regarding the test result, 97 (52.7%) were positive for influenza.
      Significantly more oseltamivir and less antibiotic treatment were prescribed to
      patients with positive test result compared with those with a negative test
      result. Additionally, the impact of the test in the participating physicians'
      decision making was obvious, as doctors who used the test systematically
      prescribed significantly more oseltamivir and less antibiotic treatment compared
      to the doctors who didn't use the test. CONCLUSION: The use of a rapid test for
      seasonal influenza enabled the targeted treatment with oseltamivir, as well as a
      reduction in antibiotic treatment, in patients found positive for influenza in
      our clinical setting.

PMID- 20816601
TI  - Mild heart failure is a mortality marker after a non-ST-segment acute myocardial
      infarction.
AB  - BACKGROUND: The Killip classification categorizes heart failure (HF) in acute
      myocardial infarction, and has a prognostic value. Although non-ST-elevation
      myocardial infarction (NSTEMI) is increasing steadily, little information is
      available about the prognostic value of low Killip class in this scenario. Our
      aim was to assess the prognostic value of mild HF in NSTEMI. METHODS: 835
      patients with NSTEMI between 2005 and 2007 were prospectively recruited. Patients
      in Killip-1 (K1=684) or Killip-2 class (K2=113) were selected (38, with K>2,
      excluded). Clinical, angiographic, treatment strategies, and 30-day all-cause
      mortality, together with other cardiovascular outcomes were recorded. RESULTS: K2
      patients were mostly women (K1 27.9% vs K2 48.0%, p<0.001) and older (K1
      66.6years vs K2 73.8years, p<0.001) with a higher frequency of diabetes mellitus
      (p<0.001) and hypertension (p<0.001). Smoking was less frequent in the K2-group
      (p=0.003). A previous infarction/revascularization history was similar in both
      groups. The infarction size, assessed by Troponin I/Creatin kinase, did not
      differ between groups (p=0.378 and p=0.855). Multivessel coronary disease and
      revascularization procedures were less common in group K2 (p=0.015 and p=0.005 vs
      group K1, respectively). Patients in K2 had a worse prognosis in terms of maximum
      Killip class, death and major adverse cardiovascular events (p<0.001). After
      multivariate analysis, mild HF at presentation was an independent risk factor for
      mortality (OR=6.50; IC 95%: 2.48-16.95; p<0.001). CONCLUSION: Mild HF at
      presentation in NSTEMI is linked to a poor prognosis, with increased short-term
      mortality. Thus, a more aggressive approach including early cardiac
      catheterization and revascularization should be considered.

PMID- 20816602
TI  - Circulating levels of asymmetric dimethylarginine are an independent risk factor
      for left ventricular hypertrophy and predict cardiovascular events in pre
      dialysis patients with chronic kidney disease.
AB  - BACKGROUND: Several studies have related the circulating level of asymmetric
      dimethylarginine (ADMA) to cardiac remodeling and cardiovascular (CV) events in
      end-stage renal disease (ESRD) patients. Studies investigating this relationship
      in patients with pre-dialysis chronic kidney disease (CKD) are lacking. METHODS:
      We enrolled 76 CKD patients (age, 46.7+/-14.3 years, 39 females) and 15 controls
      (age, 40.1+/-18.5 years, 6 females). Clinical parameters, blood biochemistry and
      echocardiographic findings were recorded, and plasma ADMA concentrations measured
      by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Patients
      were prospectively followed up for a median of 15 (range, 6-24) months. RESULTS:
      Plasma ADMA was significantly elevated in CKD patients compared with controls
      (41.56+/-12.76 microg/mL vs 17.12+/-7.09 microg/mL, P<0.001), and correlated with
      the left ventricular mass index (LVMI) (r=0.597, P<0.001). During follow-up, 25
      patients experienced new CV events and their plasma ADMA level was significantly
      elevated (48.27+/-13.70 vs 34.91+/-6.38 in CV event-free patients, P<0.001). Cox
      regression analysis further confirmed that ADMA was an independent risk factor
      for CVD (HR=1.175, 95%CI[1.070-1.290], P=0.001). CONCLUSION: Similar to findings
      in ESRD patients, elevated circulating levels of ADMA may increase the risk of
      LVH and CV events in pre-dialysis CKD patients.

PMID- 20816604
TI  - Adverse drug reactions detected by stimulated spontaneous reporting in an
      internal medicine department in Romania.
AB  - BACKGROUND: It is generally recognized that adverse drug reactions (ADRs)
      represent a major concern of health systems in terms of early recognition, proper
      management and prevention. The aims of this study were to identify the most
      frequent ADRs recognized by the attending physicians, study their nature and
      target these ADRs in order to take future preventive measures. METHODS: A
      prospective study was conducted over a 12-month period in an internal medicine
      department using stimulated spontaneous reporting for identifying ADRs. All ADRs
      reported by physicians were followed up to the patient's discharge and evaluated
      by an independent group of pharmacologists. Causality, severity and
      preventability were assessed. RESULTS: Of the 1854 admissions, 112 ADRs in 94
      patients (5.07%) were validated from the total of 118 ADRs reported. The overall
      incidence of serious ADRs in the hospitalized patients was 4.7%. According to the
      MedDRA classification, the most frequent ADRs affected the gastrointestinal
      system, followed by metabolic and vascular systems. The drugs most frequently
      involved were cardiovascular agents, anticoagulants and NSAIDs. Drug interactions
      were responsible for 25.9% of ADRs. According to the selected preventability
      scale, 40.18% ADRs were classified as 'potentially preventable' and 9.82%
      'definitely preventable'. Most of the ADRs were 'type A' reactions and as such
      could have been avoided simply by adjusting the doses or by avoiding drug
      interactions. CONCLUSIONS: Serious ADRs in hospitalized patients are common and
      often preventable. Preventing strategies should target drug prescription.
      Adequate training regarding pharmacology and optimization of drug therapy might
      help reduce ADRs' morbidity and mortality.

PMID- 20816603
TI  - Common diagnoses in internal medicine in Europe 2009: a pan-European, multi
      centre survey.
AB  - OBJECTIVE: Information on the medical problems and diseases encountered by
      practicing Internists in the hospital environment is lacking. The aim of this
      study is to assess the prevalence of various diagnostic categories that present
      to internists in the hospital setting in Europe. DESIGN: A pan-European study
      used the Young Internists Research Network of the European Federation of Internal
      Medicine. RESULTS: Data on 1501 patients from 31 physicians in 18 European
      countries were included in the study. The patients carried an average of 2.75 (+/
      2.22) chronic medical diagnoses, ranging from 0 to 18. The most common presenting
      complaint was shortness of breath, followed by chest pain and abdominal pain. A
      cardiac condition was most common, followed by infectious disease. The complexity
      of patients averaged 2.5 (+/-1.14). CONCLUSIONS: The results of this study will
      be useful for the development of a modern internal medicine curriculum, both at
      the graduate and postgraduate level, which reflects the competencies required for
      the delivery of comprehensive patient care in internal medicine wards.

PMID- 20816605
TI  - Prevalence and routine assessment of unhealthy alcohol use in hospitalized
      patients.
AB  - OBJECTIVES: To determine the prevalence of alcohol misuse among medical
      inpatients and the methods used by medical staff to evaluate alcohol consumption.
      METHODS: Multicenter, prospective, observational, cross-sectional study performed
      at 21 hospitals in Spain. All adult patients hospitalized in internal medicine
      wards on 12 March 2008 were eligible for study. Alcohol consumption was evaluated
      with the Alcohol Use Disorders Identification Test (AUDIT-C and AUDIT) and the
      Systematic Inventory of Alcohol Consumption questionnaire. Drinking patterns were
      determined according to clinical evaluation using ICD-10 criteria. Medical
      records were reviewed to gather information on the recording of alcohol use.
      RESULTS: We assessed 1039 inpatients, of whom 123 (12%) had unhealthy alcohol
      drinking patterns. Alcohol misuse was more frequent among males (odds ratio
      5.20), younger patients (odds ratio, 14.17), median age patients (odds ratio,
      2.99), and South Region (odds ratio, 1.77). Alcohol use during hospitalization
      was recorded in 603 inpatients (59%); quantitative records were performed in 28%
      of hazardous and harmful drinkers and in 41% of dependent patients. Lack of
      alcohol use recording was more frequent among females (odds ratio 1.73), median
      and older age groups (odds ratios 1.44 and 1.73, respectively), Northwest Regions
      (odds ratios 3.46). Patients from the East Region (odds ratio 0.47) had more
      frequently assessed the question in their medical records. CONCLUSIONS:
      Prevalence of alcohol misuse was higher in hospitalized patients than in the
      general population. Adequate quantitative recording was infrequent. We stress the
      need to implement measures to increase and improve the detection and recording of
      alcohol use.

PMID- 20816606
TI  - New antiplatelet agents in acute coronary syndromes (ACS): an update.

PMID- 20816607
TI  - New anticoagulants in internal medicine: an update.

PMID- 20816608
TI  - IgA and IgG antibody testing for coeliac disease.

PMID- 20816610
TI  - Severe acute respiratory failure in patients with influenza A (H1N1) virus
      infection admitted in intensive care.

PMID- 20816611
TI  - Presence and diagnosis of amebic infestation in Turkish patients with active
      ulcerative colitis.

PMID- 20816612
TI  - Proceeding of the 2009 Society of Urologic Oncology Spring Meeting.

PMID- 20816613
TI  - Deciding whom to biopsy.
AB  - Biopsy results from the Prostate Cancer Prevention Trial (PCPT) showed that
      prostate cancer exists at all PSA levels and that a significant number of men
      with "normal" PSA levels have high grade cancer. These findings and the low
      specificity of total PSA in discriminating cancer from benign disease have added
      to the debate about how best to use PSA in selecting men for prostate biopsy.
      Lower PSA thresholds for consideration of biopsy, particularly in younger men,
      are advocated by some. PSA velocity measurements may assist in the identification
      of men most likely to harbor cancer, and lower PSA velocity thresholds may be
      more appropriate in younger men. A more individualized approach using a
      predictive model developed from PCPT biopsy results is promoted by others. While
      able to incorporate risk variables other than PSA, including new markers, this
      risk calculator does not include PSA velocity since this variable was not found
      to have independent predictive value in this model. This article will present
      differing viewpoints on selecting men for prostate biopsy, one advocating the use
      of a PSA cut-off or PSA velocity measure (Dr. Catalona) and the other arguing for
      the routine use of established risk nomograms (Dr. Klein).

PMID- 20816614
TI  - Limitations of a contemporary prostate biopsy: the blind march forward.
AB  - In an attempt to reduce morbidity, focal targeted therapies and active
      surveillance have become increasingly popular treatment choices for localized
      prostate cancer. However, these modalities rely heavily on accurate and reliable
      tumor localization information provided by a prostate biopsy. Evidence that our
      contemporary biopsy techniques can do little more than detect some prostate
      cancers is notably lacking. What is meant by the accuracy and reliability of a
      prostate biopsy and why they are such important concepts to focal therapy and
      active surveillance are discussed.

PMID- 20816615
TI  - Focal therapy for prostate cancer: fact or fiction?
AB  - Prostate cancer is the commonest male cancer diagnosed in men in the UK, and the
      treatment of organ confined prostate cancer is a subject of much debate. Focal
      therapy for prostate cancer intends to treat the cancer within the prostate,
      whilst sparing the majority of the benign prostate tissue. In addition, the
      intention is to avoid treatment effects in the surrounding structures, the damage
      of which leads to the side effects commonly associated with radical whole gland
      therapies. This relies on accurate localization of the prostate cancer by biopsy
      and imaging followed by treatment using a modality capable of delivery to a focal
      area within the prostate. Focal therapy lies between the current extremes of
      radical whole gland treatment and active surveillance. There have been many
      articles reviewing the concept of focal therapy for organ confined prostate
      cancer, but with a paucity of data available for analysis. This is being
      addressed with an increase in the published data on focal therapy, using a number
      of different modalities. In this review, we address the question of whether the
      data currently published does in fact support the further development of the
      focal therapy approach, or whether it is a concept best relegated to the realms
      of fiction.

PMID- 20816616
TI  - What is the optimal management of high risk, clinically localized prostate
      cancer?
AB  - OBJECTIVES: To summarize the presentations and debate regarding the optimal
      treatment of localized high-risk prostate cancer as presented at the 2009 Spring
      Meeting of the Society of Urologic Oncology. MATERIALS AND METHODS: The debate
      was centered on presentations arguing for radical prostatectomy (RP) or
      radiotherapy as the optimal treatment for this condition. The meeting
      presentations are summarized by their respective presenters herein. RESULTS: Dr.
      James Eastham presents the varied definitions for "high-risk" prostate cancer as
      strongly influencing which patients end up in this cohort. Based upon this,
      between 3% and 38% of patients with high-risk features could be defined as "high
      risk". Despite that, these men do not have a uniformly poor prognosis after RP,
      and attention to surgical principles as outlined improve outcomes. Disease
      specific survival at 12 years is excellent and up to one-half of these men may
      not need adjuvant or salvage therapies, depending on their specific disease
      characteristics. Adjuvant or salvage radiotherapies improve outcomes and are part
      of a sequential approach to treating these patients. Dr. Anthony Zietman
      presented radiotherapy as the gold-standard based upon large, randomized clinical
      trials of intermediate- and high-risk prostate cancer patients. Compared with
      androgen deprivation alone, the addition of radiotherapy provided a 12% cancer
      specific survival advantage and 10% overall survival advantage. Dose escalation
      seems to confer further improvements in cancer control without significant
      escalation of toxicities, with more data forthcoming. CONCLUSIONS: There are no
      randomized trials comparing RP to radiotherapy for any risk category. In high
      risk prostate cancer patients, both approaches have potential benefits and
      cumulative toxicities that must be matched to disease characteristics and patient
      expectations in selecting a treatment course.

PMID- 20816617
TI  - Impact of nephron sparing on kidney function and non-oncologic mortality.
AB  - The surgical management of kidney tumors has significantly evolved over the past
      decade. Partial nephrectomy and nephron sparing surgery have emerged as the
      treatments of choice for most newly diagnosed kidney tumors at tertiary care
      centers. The trend towards an organ sparing approach is largely due to an
      improved understanding of the global importance of kidney function as well as the
      impact that kidney surgery may have on non-oncologic morbidity and mortality. In
      addition to reviewing the methods of evaluating kidney function, this article
      discusses the effectiveness of various nephron sparing techniques in preserving
      kidney function and improving non-oncologic outcomes.

PMID- 20816623
TI  - Radiation dose: Walmart or mom and pop?

PMID- 20816624
TI  - If you can't say something nice, at least make it interesting.

PMID- 20816625
TI  - The radiologist as a physician consultant.

PMID- 20816626
TI  - Blinders off!

PMID- 20816627
TI  - ACR Appropriateness Criteria on colorectal cancer screening.
AB  - Colorectal cancer remains one of the most common causes of cancer death in this
      country. This malignancy is ideally suited for screening because the detection
      and removal of the precursor adenomatous polyp can prevent most colorectal
      cancers from ever forming. The choice of a test for screening involves
      consideration of various individual parameters, including patient age and the
      presence of risk factors for the development of colorectal cancer. Computed
      tomographic colonography (CTC) has emerged as the leading imaging technique for
      colorectal cancer screening in average-risk individuals on the basis of the
      evidence presented in this paper. The double-contrast barium enema is an
      alternative imaging test that is appropriate particularly when CTC is not
      available. In 2008, the American Cancer Society guideline for colorectal cancer
      screening was revised jointly with the US Multi-Society Task Force on Colorectal
      Cancer and the ACR to include CTC every 5 years as an option for average-risk
      individuals. Computed tomographic colonography is also the preferred test for
      colon evaluation after an incomplete colonoscopy. Imaging tests including CTC and
      the double-contrast barium enema are usually not indicated for colorectal cancer
      screening in high-risk patients with polyposis syndromes or inflammatory bowel
      disease. This paper presents the new colorectal cancer imaging test ratings and
      is the result of evidence-based consensus by the ACR Appropriateness Criteria
      Expert Panel on Gastrointestinal Imaging.

PMID- 20816628
TI  - Special communication--occupational health hazards in the interventional
      laboratory: progress report of the multispecialty occupational health group.
AB  - The Multispecialty Occupational Health Group (MSOHG), formed in 2005, is an
      informal coalition of societies representing professionals who work in or are
      concerned with interventional fluoroscopy. The group's long-term goals are to
      improve occupational health and operator and staff safety in the interventional
      laboratory while maintaining quality patient care and optimal use of the
      laboratory. MSOHG has conducted a dialogue with equipment manufacturers and has
      developed a list of specific objectives for research and development. The group
      has also represented the member societies in educating regulators, in educating
      interventionalists, and in fostering and collaborating on research into
      occupational health issues affecting interventionalists. Not least of the group's
      accomplishments, as a result of their collaboration in MSOHG, the group's members
      have developed a mutual respect that can serve as a basis for joint efforts in
      the future among interventionalists of different medical specialties.

PMID- 20816629
TI  - Financing research and education: current challenges and future solutions--a
      summary of the 2009 Intersociety Conference.
AB  - Academic radiology departments perform the majority of the educational and
      research functions that support and grow our specialty; however, these missions
      are financed heavily from the clinical revenue generated by academic
      radiologists. This financial dependence on an uncertain revenue stream places our
      academic missions at considerable risk and strains the solvency of our academic
      base. Distributing the costs of education and research across the primary
      beneficiaries of the education and research product would lessen the burden on
      our academic departments and create a more stable financial base for the future.

PMID- 20816630
TI  - The role of radiology in influenza: novel H1N1 and lessons learned from the 1918
      pandemic.
AB  - The pandemic of swine-origin H1N1 influenza that began in early 2009 has provided
      evidence that radiology can assist in the early diagnosis of severe cases,
      raising new opportunities for the further development of infectious disease
      imaging. To help define radiology's role in present and future influenza
      outbreaks, it is important to understand how radiologists have responded to past
      epidemics and how these outbreaks influenced the development of imaging science.
      The authors review the role of radiology in the most severe influenza outbreak in
      history, the "great pandemic" of 1918, which arrived only 23 years after the
      discovery of x-rays. In large part because of the coincidental increase in the
      radiologic capacity of military hospitals for World War I, the 1918 pandemic
      firmly reinforced the role of radiologists as collaborators with clinicians and
      pathologists at an early stage in radiology's development, in addition to
      producing a radical expansion of radiologic research on pulmonary infections.
      Radiology's solid foundation from the 1918 experience in medical practice and
      research now affords significant opportunities to respond to the current H1N1
      pandemic and future epidemics through similar interdisciplinary strategies that
      integrate imaging science with pathology, virology, and clinical studies. The
      broad range of current imaging capabilities will make it possible to study
      influenza at the cellular level, in animal models, and in human clinical trials
      to elucidate the pathogenesis of severe illness and improve clinical outcomes.

PMID- 20816631
TI  - Long radiology workdays reduce detection and accommodation accuracy.
AB  - PURPOSE: The aim of this study was to measure the diagnostic accuracy of fracture
      detection, visual accommodation, reading time, and subjective ratings of fatigue
      and visual strain before and after a day of clinical reading. METHODS: Forty
      attending radiologists and radiology residents viewed 60 deidentified, HIPAA
      compliant bone examinations, half with fractures, once before any clinical
      reading (early) and once after a day of clinical reading (late). Reading time was
      recorded. Visual accommodation (the ability to maintain focus) was measured
      before and after each reading session. Subjective ratings of symptoms of fatigue
      and oculomotor strain were collected. The study was approved by local
      institutional review boards. RESULTS: Diagnostic accuracy was reduced
      significantly after a day of clinical reading, with average areas under the
      receiver operating characteristic curves of 0.885 for early reading and 0.852 for
      late reading (P < .05). After a day of image interpretation, visual accommodation
      was no more variable, though error in visual accommodation was greater (P < .01),
      and subjective ratings of fatigue were higher. CONCLUSIONS: After a day of
      clinical reading, radiologists have reduced ability to focus, increased symptoms
      of fatigue and oculomotor strain, and reduced ability to detect fractures.
      Radiologists need to be aware of the effects of fatigue on diagnostic accuracy
      and take steps to mitigate these effects.

PMID- 20816632
TI  - Stability and infrequency of radiologic technologist malpractice payments: an
      analysis of the National Practitioner Data Bank.
AB  - PURPOSE: The aim of this study was to describe characteristics and trends of
      radiologic technologist (RT) malpractice payments. METHODS: National Practitioner
      Data Bank data files were analyzed for details of RT malpractice payments from
      1991 through 2008. Payment amounts, sources, and allegations were all identified
      and summarized, along with geographic and demographic data. RESULTS: Between 1991
      and 2008, a total of 155 RT malpractice payments were reported nationally,
      ranging from $750 to $11.5 million (median, $57,500; mean, $293,655 +/-
      $1,305,091), with 153 (99%) <$1 million. Adjusting for outliers and inflation,
      payments changed little over the 18-year interval. More than half of all cases
      originated in 8 states, with per capita payments most common in Louisiana and New
      Jersey. Alleged errors in diagnosis accounted for one third of all cases.
      CONCLUSION: Malpractice payments on behalf of RTs are very infrequent (on
      average, <9 nationally each year) and usually relatively small (almost half
      <$50,000). Frequency and mean adjusted payment have remained stable over nearly
      two decades, likely related in part to "deep pocket" shielding by hospitals and
      radiologists.

PMID- 20816633
TI  - PowerPoint: know your medium.
AB  - To make the most of PowerPoint in professional presentations, presenters need to
      understand some basic principles that transcend the software. These include a
      thorough grasp of the message a presenter wants to convey; the backgrounds,
      interests, and needs of the audience; and the best approaches to fitting the
      medium of delivery to the content of the material. PowerPoint is a useful tool,
      but like any tool, whether a stethoscope, a scalpel, or a CT scanner, it can be
      used well or ill. Using it to its full capabilities requires that we regard it
      less as a crutch that can compensate for our deficiencies and more as a
      springboard with which to vault our presentations higher. At its best, PowerPoint
      can serve us just as brushes and pigments serve an artist, but it can never
      substitute for a fertile imagination and a discerning eye.

PMID- 20816634
TI  - The impact of an early-morning radiologist work shift on the timeliness of
      communicating urgent imaging findings on portable chest radiography.
AB  - PURPOSE: The aim of this study was to assess the potential impact of staggered
      radiologist work shifts on the timeliness of communicating urgent imaging
      findings that are detected on portable overnight chest radiography of
      hospitalized patients. METHODS: The authors conducted a retrospective study that
      compared the interval between the acquisition and communication of urgent
      findings on portable overnight critical care chest radiography detected by an
      early-morning shift for radiologists (3 am to 11 am) with historical experience
      with a standard daytime shift (8 am to 5 pm) in the detection and communication
      of urgent findings in a similar patient population a year earlier. RESULTS:
      During a 4-month period, 6,448 portable chest radiographic studies were
      interpreted on the early-morning radiologist shift. Urgent findings requiring
      immediate communication were detected in 308 (4.8%) studies. The early-morning
      shift of radiologists, on average, communicated these findings 2 hours earlier
      compared with the historical control group (P < .001). CONCLUSION: Staggered
      radiologist work shifts that include an early-morning shift can improve the
      timeliness of reporting urgent findings on overnight portable chest radiography
      of hospitalized patients.

PMID- 20816635
TI  - Mentoring medical students in radiation oncology.
AB  - Mentoring in academic medicine has been described on a multitude of levels in
      medical literature, but seldom with respect to medical students. In fact,
      although some fields have addressed mentoring in the context of medical student
      education, radiation oncology has yet to do so in a comprehensive fashion.
      Furthermore, the projected domestic and worldwide epidemiologic trends in cancer
      cases, coupled with the frequent use of radiation-based cancer treatment
      regimens, make this an opportune moment to initiate such a discussion. Herein,
      the authors consider mentoring in the context of radiation oncology and related
      fields from the perspective of a medical student. They present a paradigm for
      promoting mentorship through traditional classroom-based and nontraditional
      socially and research-based initiatives. It is the authors' hope that both
      radiation oncology and other specialties will benefit from the initiation of this
      discussion, as well as build on the suggestions detailed here as we prepare the
      next generation of radiation oncologists.

PMID- 20816636
TI  - Your best ROI/cover your assets.

PMID- 20816637
TI  - Independent contractor or employee? Higher stakes for many medical practices.

PMID- 20816638
TI  - Radiology practice in Kuwait: ambitions and obstacles.

PMID- 20816639
TI  - Identification of retained surgical foreign objects: policy at a university
      medical center.

PMID- 20816640
TI  - Current IGRT, SBRT, and SRS procedures and reimbursement.

PMID- 20816641
TI  - John Diaconis.

PMID- 20816642
TI  - Can virtual chromoendoscopy measure up to histology in early gastric cancer?

PMID- 20816643
TI  - Study of the binding residues between ANEPII and insect sodium channel receptor.
AB  - The present study aimed at determining the functional characteristics of anti
      neuroexcitation peptide II (ANEPII). The depressant insect toxin ANEPII from the
      Chinese scorpion Buthus martensii Karsch had an effect on insect sodium channels.
      Previous studies showed that scorpion depressant toxins induce insect flaccid
      paralysis upon binding to receptor site-4, so we tried to predict the functional
      residues involved using computational techniques. In this study, three
      dimensional structure modeling of ANEPII and site-4 of the insect sodium channel
      were carried out by homology modeling, and these models were used as the starting
      point for nanosecond-duration molecular dynamics simulations. Docking studies of
      ANEPII in the sodium channel homology model were conducted, and likely ANEPII
      binding loci were investigated. Based on these analyses, the residues Tyr34,
      Trp36, Gly39, Leu40, Trp53, Asn58, Gly61 and Gly62 were predicted to interact
      with sodium channel receptor and to act as functional residues.

PMID- 20816644
TI  - Lipid components of olive oil from Tunisian Cv. Sayali: characterization and
      authenticity.
AB  - The analysis of the total lipid fraction from the Sayali variety of olive oil was
      accomplished in the present investigation. Glyceridic, unsaponifiable and flavour
      fractions of the oil were isolated and identified using several analytical
      methods. Chromatographic techniques have proven to be suitable for these
      determinations, especially capillary gas chromatography. Gas chromatography
      coupled to mass spectrometry was successfully used to identify sterols,
      triterpenes alcohols, 4-monomethylsterols, aliphatic alcohols and aroma compounds
      in our samples. Furthermore, solid phase microextraction was used to isolate
      volatiles from the total lipid fraction. Results from the quantitative
      characterization of Sayali olive oil showed that oleic acid (77.4%) and triolein
      (47.4%) were the dominant glyceridic components. However, the main compounds of
      the unsaponifiable fraction were beta-sitosterol (147.5mg/100g oil), 24-methylene
      cycloartenol (146.4mg/100g oil) and hexacosanol (49.3mg/100g oil). Moreover,
      results showed that the aldehydic compounds were the major flavours present in
      Sayali olive oil.

PMID- 20816645
TI  - [Systematic of the Gobiidae Lophogobius cyprinoides (Pallas, 1770)].
AB  - DIAGNOSIS: number of fins rays D1: VI; D2: I+9; C: 21-22; A: I+8; P: 17-18; Pv:
      10; number of scales on the lateral line Ec: 27-28; number of vertebras V: 26.
      Evidence of sexual dimorphism is shown by two different shapes of urogenital
      papilla. The lateral system was observed using scanning electron microscopy after
      2% glutaraldehyde fixation in sea water. The oculoscapular, preopercular canals,
      mucous pores are inventoried and the distribution and number of neuromasts are
      presented. The coding sequences for 18S ribosomic RNA are identified.

PMID- 20816646
TI  - Assessment of polyphenolic compounds, in vitro antioxidant and anti-inflammation
      properties of Securidaca longepedunculata root barks.
AB  - The present study was carried out to evaluate the antioxidant activities of the
      root bark extract of Securidaca longepedunculata. This plant material is commonly
      used in folk medicine in several parts in the world. The bark extracts of S.
      longepedunculata were evaluated for their total phenols, flavonoids,
      anthocyanins, tannins content and total antioxidant capacity. The compounds were
      identified and quantified both by RP-HPLC and UV spectrophotometer; the
      antioxidant capacity was assessed by ABTS and DPPH tests and expressed as IC(50).
      The total phenolic compounds determinate was 9.86mg gallic acid equivalents/g dw,
      the total flavonoid contents was 5.85mg catechin equivalents/g dw, the total
      anthocyanin contents was 0.032mg cyanidin-3-glycosyl equivalents/g dw and the
      condensed tannins content were 1.03mg catechin equivalents/g dw. The major
      compound identified using RP-HPLC was quercetin (0.98mg/ml). The IC(50) value
      reached 5.5microg/ml, revealing that the root barks of S. longepedunculata have a
      very high antioxidant and anti-inflammation properties.

PMID- 20816647
TI  - Impact of grazing on the species richness of plant communities in Mediterranean
      temporary pools (western Morocco).
AB  - The impact of grazing on the vegetation of Moroccan temporary pools has been
      studied at 2 scales: regional (inter-pools) and local (intra-pools). Half of the
      16 forest pools studied is located in a reserve and ungrazed. The other half,
      located within public forest, is grazed. Vegetation releves coupled to water
      depths measurements were carried out in each pool. The results showed a
      significant effect of grazing on both scales of analysis. This effect was found
      in the species composition of the vegetation, which differed between the 2 types
      of pools, and in the lower species richness and abundance of plant species in the
      grazed pools. These differences are interpreted as resulting from the selection
      by herbivores and the differential tolerance of species to disturbance. These
      impacts are likely to expose certain species to local extinction by reducing
      their populations.

PMID- 20816648
TI  - Morphometric analysis of six Gerbillus species (Rodentia, Gerbillinae) from
      Tunisia.
AB  - Size and shape changes in the skull of the genus Gerbillus were investigated
      using geometric morphometrics. Six species from Tunisia were studied (G.
      gerbillus, G. campestris, G. nanus, G. tarabuli, G. simoni and G. latastei).
      Statistical analyses of shape variability allowed us to discriminate three
      morphological groups which are congruent with the three groups suggested by
      previous morphological and molecular studies. However, our results contrast with
      previous molecular investigations. In fact, according to results obtained by the
      use of principal component analysis, canonical variate analysis and UPGMA, we
      found a higher degree of divergence between the subgenus Dipodillus and the other
      two subgenera Gerbillus and Hendecapleura. This fact suggests that the
      morphometric differences observed among species within the genus Gerbillus are
      not mainly related to phylogeny. To reconciliate the molecular and morphological
      approaches, we propose a hypothesis of differential rates of phenotypic evolution
      in the genus Gerbillus. In this view, the species belonging to the subgenus
      Dipodillus evolved apomorphic features of the skull likely related to a higher
      degree of habitat specialization. By contrast, the more generalist Gerbillus and
      Hendecapleura subgenera show less differentiated plesiomorphic morphology.

PMID- 20816649
TI  - Begging coordination between siblings in Black-headed Gulls.
AB  - Communication behaviours are now considered from a signallers-receivers network
      perspective. This concept seems well suited to the study of interactions between
      parents and offspring in birds, so far mainly treated as a dyadic signalling
      system involving the brood or a single chick as a signaller and the parent as a
      receiver. Family conflicts over resource allocation drive parent-offspring and
      sib-sib communication. In the Black-headed Gull Larus ridibundus, parents respond
      to the whole-brood begging intensity and siblings often synchronize their begging
      signalling thus limiting individual effort. By monitoring five nests of two-chick
      broods during the whole rearing period in the nest, we show how an intra-brood
      simultaneity of begging emerges from successive phases of solitary begging of
      junior and senior nestlings. Although this result remains preliminary due to the
      sample size, it underlines a dynamical aspect of chicks' behaviour. Because they
      always favour coordinated begging and because they elevate their response
      threshold across the rearing period, parents may play a major role in the
      plasticity of begging behaviour.

PMID- 20816650
TI  - Patterns of emblematic habitat types in Mediterranean temporary wetlands.
AB  - This article presents the floristic, structural, and syntaxonomical features of
      plant assemblages in temporary wetlands and the pattern of the corresponding
      habitat types; according to the Habitats Directive. Nine pristine temporary
      wetlands covering a wide range of shapes, elevations and substrates were
      monitored. The "within temporary wetlands" hydrological gradient was strong
      enough to drive the vegetation and habitat type patterns. Plant assemblages
      presented a spatial arrangement in three concentric belts repeatedly present in
      each site in the same relative position. The presence of the H3120 habitat type
      was recognized in the central and in the intermediate belt. The outer belt was
      the more suitable for the presence of the H3170* priority habitat. Therefore, it
      should represent the main conservation target within temporary wetlands. On the
      other hand, it was the smallest in size (only 13% of the total surface) and in
      some cases absent, inconspicuous, or severely fragmented.

PMID- 20816651
TI  - Child health policy: where are you when we need you?

PMID- 20816652
TI  - Health reform and beyond: delivering results for children.

PMID- 20816653
TI  - Individualized learning plans: basics and beyond.

PMID- 20816654
TI  - Premature infants born to adolescent mothers: health care utilization after
      initial discharge.
AB  - OBJECTIVE: Premature infants have increased health care utilization after initial
      discharge compared with term infants. Young maternal age has been shown to impact
      health care utilization among term infants, but little is known about the impact
      of maternal age on health care utilization among premature infants. We compared
      health care utilization among premature infants of adolescent (aged < or = 19
      years) and young adult (aged 20-29 years) mothers, hypothesizing that premature
      infants of adolescent mothers would have increased acute care utilization, while
      having decreased preventive care utilization. METHODS: In this retrospective
      cohort study, we analyzed health care utilization of premature infants born to
      adolescent mothers (n = 76) compared with premature infants born to young adult
      mothers (n = 587) within a cohort of premature infants born between 1998 and 2001
      in an integrated health care delivery system. RESULTS: After controlling for
      illness severity, premature infants born to adolescent mothers had significantly
      increased odds of medical rehospitalizations (odds ratio 3.57, 95% confidence
      interval, 1.81-7.05) and emergency department visits (odds ratio 3.67, 95%
      confidence interval, 2.11-6.39) during the first year after initial discharge
      compared with premature infants born to young adult mothers. Differences in
      rehospitalization rates were significant within the first 3 months after
      discharge (P < .001). Frequency of preventive care visits was not significantly
      different between the two groups. CONCLUSIONS: Despite similar severity of
      chronic illness and similar preventive care utilization, premature infants born
      to adolescent mothers had significantly increased rates of rehospitalizations and
      emergency department visits compared with premature infants born to young adult
      mothers.

PMID- 20816655
TI  - The importance of early parenting in at-risk families and children's social
      emotional adaptation to school.
AB  - OBJECTIVE: The aim of this study was to determine the specific aspects of early
      parenting in psychosocially at-risk families most strongly related to children's
      social-emotional adaptation to school. METHODS: A cohort study of families (N =
      318) identified as at risk for maltreatment of their newborns was conducted.
      Quality of early parenting was observed in the home when the child was 1 year
      old. Social-emotional adaptation to school was reported by teachers in first
      grade. Multivariable models assessed the independent influence of early parenting
      variables on social-emotional adaptation. RESULTS: Early parenting and social
      emotional adaptation to school varied greatly across families. Parental warmth
      was associated with lower teacher ratings of shyness, concentration problems, and
      peer rejection. Parental lack of hostility was associated with decreased teacher
      ratings of concentration problems and peer rejection. Parental encouragement of
      developmental advance was associated with lower ratings of aggression and peer
      rejection. Provision of materials to promote learning and literacy was associated
      with lower ratings of concentration problems. CONCLUSIONS: In this sample of
      families with multiple psychosocial risks for child maltreatment, specific
      aspects of early parenting were associated with better social-emotional
      adaptation to school in the first grade in theoretically predicted ways.
      Improving parental knowledge about positive parenting via anticipatory guidance
      should be a focus of well-child visits. Well-child visit-based interventions to
      improve the quality of early parenting, especially among at-risk families, should
      be studied for their impact on parenting behavior and on children's successful
      social-emotional adaptation to school. Primary care providers should reinforce
      complementary services, such as home visiting, that seek to promote positive
      parenting.

PMID- 20816656
TI  - Factors associated with discipline counseling for parents of infants and young
      children.
AB  - OBJECTIVE: The aim of this study was to identify and better understand the
      factors associated with discipline counseling at health visits and how parents'
      needs for discipline counseling are being met. METHODS: Cross-sectional data
      analyses from the 2000 National Survey of Early Childhood Health. Participants
      were 1216 parents of children aged between 10 and 35 months. Main outcome
      measures were parents' reports that their health care provider discussed
      discipline practices with them in the previous year, and if not, whether this
      would have been helpful (an unmet need). RESULTS: Discipline counseling was more
      common when the health care provider discussed other developmental and
      psychosocial topics, did a developmental assessment, received higher ratings of
      family centered care and provided longer visits, and when parents indicated
      having the opportunity to ask all their questions. However, parents who reported
      less support for child rearing and parents who reported greater use of spanking
      were less likely to receive discipline counseling. Spanish-speaking Hispanic
      parents and parents who reported less support were more likely to report an unmet
      need for discipline counseling. Higher income respondents were less likely to
      report an unmet need for discipline counseling. CONCLUSION: Discipline counseling
      at health visits is associated with a family-centered orientation and the
      delivery of other developmental and psychosocial services. However, many parents
      who might have benefited from discipline counseling were less likely to receive
      it and more likely to report this as an unmet need. These data suggest that
      discipline counseling may be more accurately tailored to parents most likely to
      benefit.

PMID- 20816657
TI  - Canine visceral leishmaniasis in Teresina, Brazil: Relationship between clinical
      features and infectivity for sand flies.
AB  - Leishmania chagasi is an intracellular parasite transmitted by the bite of the
      phlebotomine sand fly Lutzomyia longipalpis, which is the most important of
      American visceral leishmaniasis. In the gut of the vector, amastigoste forms of
      the parasite transform into metacyclic promastigotes, from there to the foregut,
      where they could be transmitted in the next blood meal. Xenodiagnosis is an
      important tool for the detection of Leishmania, especially when associated to
      molecular techniques, both being useful for the monitoring and evaluation of dog
      infectivity in endemic areas. In this study, direct search of Leishmania from
      material obtained through xenodiagnosis performed in dogs captured in Teresina
      (Piaui State, Brazil) identified that the predominant forms of the parasite were
      the procyclic and metacyclic forms located in the hindgut, detected between the
      5th and 6th day after the blood meal. Using polymerase chain reaction (PCR), we
      revealed that dogs with different clinical status were able to infect
      phlebotomines, the rates of sand fly infection being higher for symptomatic dogs
      (13%) as compared to asymptomatic ones (3.5%). The direct search was able to
      demonstrate infection only in phlebotomines in which the blood meal was performed
      on symptomatic dogs, with a rate of infection of 1.6%. The results underline the
      importance of using PCR and xenodiagnosis for the detection of Leishmania sp. And
      for the evaluation of infectivity of dogs in endemic areas, especially those that
      are asymptomatic.

PMID- 20816658
TI  - Usefulness of various MRI sequences in the diagnosis of viral encephalitis.
AB  - There is paucity of studies regarding the utility of various conventional MRI
      sequences in the diagnosis of viral encephalitis. The present study evaluates the
      usefulness of various MRI sequences in acute viral encephalitis. 88 consecutive
      viral encephalitis patients, aged 2-72 years were subjected to clinical
      evaluation. Consciousness was assessed by Glasgow Coma Scale (GCS). Serum or
      cerebrospinal fluid (CSF) was analyzed for dengue, Japanese encephalitis (JE),
      herpes, measles, echo, coxsackie and polio viruses using ELISA or PCR. Cranial
      MRI was done and T1, T2, FLAIR and DW images were obtained. The MRI changes were
      correlated with type of encephalitis and duration of illness. All the patients
      had altered sensorium and 37 had seizures. 22 patients had JE, 9 had dengue, 8
      had herpes simplex encephalitis (HSE), 2 had Epstein-Barr virus encephalitis
      (EBVE) and 47 had non-specific encephalitis. The median duration of MRI study
      from onset was 10 days. In JE (20/22), HSE (8/8), and EBVE (2/2), MRI
      abnormalities were more common compared to dengue (2/9) and non-specific (20/47)
      encephalitis. The MRI abnormalities were more common in FLAIR (57.1%) compared to
      T2 (52.9%), DWI (38.1%) and T1 (19.3%) sequences. The mean ADC value in JE
      patients was lower (974.0+/-110.85*10-6 mm2/s) than HSE (1024.33+/-485.76*10-6
      mm2/s). Additional MRI lesions were seen in 12.6% cases on FLAIR sequence. FLAIR
      and T2 sequences were more sensitive in revealing abnormalities in viral
      encephalitis.

PMID- 20816659
TI  - Enhancing the stability of 18O-labeled peptides through removal of immobilized
      trypsin by ZipTips.
AB  - Trypsin-catalyzed 18O labeling is increasingly used in shotgun proteomics for
      relative peptide/protein quantitation. However, precise quantitative measurements
      are often complicated by the instability of 18O-labeled peptides caused mainly by
      oxygen back-exchange. Although a number of attempts have been made to reduce or
      prevent oxygen back-exchange, there is still room for improvement. Here we
      demonstrate that the removal of immobilized trypsin by filtration using ZipTips
      can efficiently minimize oxygen back-exchange and enhance the stability of 18O
      labeled peptides under various pH conditions. The 18O-labeled peptides processed
      by the approach were successfully separated by immobilized pH gradient
      isoelectric focusing (IPG-IEF), and no marked decrease in the extent of labeling
      was observed. The results also demonstrated that there was no correlation between
      the extent of 18O labeling and molecular weight or isoelectric point (pI). The
      approach presented here is especially applicable to microscale samples. Its
      ability to generate stably 18O-labeled samples without back-exchange should
      expand the application scope of the 18O-labeling technique.

PMID- 20816660
TI  - Monitoring nonenzymatic glycation of human immunoglobulin G by methylglyoxal and
      glyoxal: A spectroscopic study.
AB  - The accumulation of dicarbonyl compounds, methylglyoxal (MG) and glyoxal (G), has
      been observed in diabetic conditions. They are formed from nonoxidative
      mechanisms in anaerobic glycolysis and lipid peroxidation, and they act as
      advanced glycation endproduct (AGE) precursors. The objective of this study was
      to monitor and characterize the AGE formation of human immunoglobulin G (hIgG) by
      MG and G using ultraviolet (UV) and fluorescence spectroscopy, circular dichroism
      (CD), and matrix-assisted laser desorption/ionization-mass spectrometry (MALDI
      MS). hIgG was incubated over time with MG and G at different concentrations.
      Formation of AGE was monitored by UV and fluorescence spectroscopy. The effect of
      AGE formation on secondary structure of hIgG was studied by CD. Comparison of AGE
      profile for MG and G was performed by MALDI-MS. Both MG and G formed AGE, with MG
      being nearly twice as reactive as G. The combination of these techniques is a
      convenient method for evaluating and characterizing the AGE proteins.

PMID- 20816661
TI  - A disposable immunosensor for Shigella flexneri based on multiwalled carbon
      nanotube/sodium alginate composite electrode.
AB  - A novel Shigella flexneri immunosensor based on horseradish peroxidase-labeled
      antibodies to S. flexneri (HRP-anti-S. flexneri) immobilized by physical
      adsorption on the multiwalled carbon nanotube (MWCNT)/sodium alginate (SA)
      composite modified screen-printed electrode surface was successfully fabricated.
      In this strategy, MWCNT/SA biocomposite acted as the matrix to adsorb and
      immobilize HRP-anti-S. flexneri. The modified electrodes were characterized with
      an atomic force microscope and cyclic voltammetry (CV). The analytical
      performance of the proposed immunosensor toward S. flexneri was investigated by
      CV. Under optimal conditions, the linear range of S. flexneri was from 104 to
      1011 cfu/ml with a detection limit of 3.1*103 cfu/ml (signal/noise=3). The
      specificity, reproducibility, stability, and accuracy of the proposed
      immunosensor were also evaluated. The proposed immunosensor showed simply
      fabricative, economical, efficient, and potential application for early
      assessment of S. flexneri.

PMID- 20816662
TI  - Production of human CD59-transgenic pigs by embryonic germ cell nuclear transfer.
AB  - This study was performed to produce transgenic pigs expressing the human
      complement regulatory protein CD59 (hCD59) using the nuclear transfer (NT) of
      embryonic germ (EG) cells, which are undifferentiated stem cells derived from
      primordial germ cells. Because EG cells can be cultured indefinitely in an
      undifferentiated state, they may provide an inexhaustible source of nuclear donor
      cells for NT to produce transgenic pigs. A total of 1980 NT embryos derived from
      hCD59-transgenic EG cells were transferred to ten recipients, resulting in the
      birth of fifteen piglets from three pregnancies. Among these offspring, ten were
      alive without overt health problems. Based on PCR analysis, all fifteen piglets
      were confirmed as hCD59 transgenic. The expression of the hCD59 transgene in the
      ten living piglets was verified by RT-PCR. Western analysis showed the expression
      of the hCD59 protein in four of the ten RT-PCR-positive piglets. These results
      demonstrate that hCD59-transgenic pigs could effectively be produced by EG cell
      NT and that such transgenic pigs may be used as organ donors in pig-to-human
      xenotransplantation.

PMID- 20816663
TI  - Modulation of the mechano-chemical properties of myosin V by drebrin-E.
AB  - The regulation of actin filament networks by various proteins has essential roles
      in the growth cone dynamics. In this study we focused on the actin-myosin
      interaction which has been suggested to be an important player in the neurite
      extension. We examined in vitro how the decoration of actin filaments with a side
      binding protein, drebrin-E, affects the motile properties of an intracellular
      transporter myosin V. Single myosin V molecules landed on the drebrin-E-decorated
      actin filaments with a lower frequency and ran over shorter distances; however,
      their velocities were normal. Furthermore, the analysis of the movement of myosin
      V molecules in the optical trap revealed that the decoration of actin filaments
      with drebrin-E markedly increased the load-sensitivity of the myosin V stepping.
      These results are attributable to the delay in the attachment of the motor's
      leading head (ADP.P(i) state) to actin, induced by the competitive binding of
      drebrin-E to actin, whereas the rate of ADP release from the trailing head (the
      rate-limiting step in the ATPase cycle of myosin V) is unaffected. Our study
      indicates that, in addition to the regulation of binding affinity of myosin V,
      drebrin-E also modulates the chemo-mechanical coupling in the motile myosin V
      molecules, presumably affecting the movement of the growth cone.

PMID- 20816664
TI  - Testosterone-induced hypertrophy of L6 myoblasts is dependent upon Erk and mTOR.
AB  - Testosterone increases the size and strength of skeletal muscle. This study
      further characterized the molecular mechanisms of the anabolic actions of
      testosterone on a rat myoblast cell line (L6 cells). Testosterone did not induce
      hypertrophy in L6 cells lacking the androgen receptor (AR). Hypertrophy was
      prevented by the AR antagonist bicalutamide and the mTOR inhibitor rapamycin.
      Testosterone induced Erk phosphorylation by 2h, and mTOR autophosphorylation was
      elevated within 20min; phosphorylation of p70S6 kinase was increased by 2h.
      Inhibitors of Erk or PI3K blocked tesotosterone-induced hypertrophy. Erk
      phosphorylation returned to baseline when media containing testosterone was
      replaced at 16h with fresh media lacking testosterone; when bicalutamide was
      added to testosterone-enriched media at 16h, Erk phosphorylation remained
      elevated. Autophosphorylation of the IGF-1 receptor was minimally altered by
      testosterone at 20min and unaffected at later time points; PI3K/PDK1-dependent
      phosphorylation of Akt was not altered by testosterone. These findings indicate
      that testosterone stimulates hypertrophy of L6 myoblasts through a mechanism that
      requires its binding to the AR and involves a signaling cascade dependent upon
      Erk and mTOR which is likely activated by substances released into the
      extracellular space which are not IGF-1 or other ligands for receptor tyrosine
      kinases.

PMID- 20816665
TI  - A novel ncRNA gene from mouse chromosome 5 trans-splices with Dmrt1 on chromosome
      19.
AB  - Dmrt1 (Dsx- and Mab3-related transcription factor-1), a conserved transcription
      factor in different phyla, is a key regulator in sex determination. Here, we
      report the novel ncRNA gene Dmr (Dmrt1-related gene), from mouse chromosome 5
      that trans-splices with Dmrt1 from chromosome 19 to generate a Dmrt1 protein that
      lacks the C-terminus. Dmr is mouse and rat specific, and the surrounding genes
      are also conserved in both species. Dmr is alternatively spliced, and three
      isoforms, Dmr a, b and c, are detected in the testis. Further, Dmr serves mainly
      as a 3' UTR, promotes trans-splicing and down-regulates the Dmrt1 protein. These
      results suggest that Dmr might play a negative regulatory role for Dmrt1 in male
      sexual development.

PMID- 20816666
TI  - Sclerostin is a direct target of osteoblast-specific transcription factor
      osterix.
AB  - Osterix (Osx) is an osteoblast-specific transcription factor required for
      osteoblast differentiation and bone formation. Osx knock-out mice lack bone
      completely. Recent findings that Osx inhibits Wnt signaling provide a feedback
      control mechanism involved in bone formation. Mechanisms of Osx inhibition on Wnt
      signaling are not fully understood. Our results in this study revealed that the
      expression of a Wnt antagonist Sclerostin (Sost) was downregulated in Osx-null
      calvaria. Overexpression of Osx in stable C2C12 mesenchymal cell line resulted in
      Sost upregulation. Transient transfection assay showed that Osx activated 1kb
      Sost promoter reporter activity in a dose-dependent manner. To define Sost
      promoter activated by Osx, we made a series of deletion mutants of Sost
      constructs, and narrowed down the minimal region to the proximal 260bp. Gel shift
      assay indicated that Osx bound to GC-rich site within this minimal region, and
      that point mutations of this binding site disrupted Osx binding. Moreover, the
      same point mutations in 260bp Sost promoter reporter disrupted the promoter
      activation by Osx, suggesting that the GC-rich binding site was responsible for
      Sost promoter activation by Osx. To further examine physical association of Osx
      with Sost promoter in vivo, Chromatin immunoprecipitation (ChIP) assays were
      performed using primary osteoblasts from mouse calvaria. Osx was found to
      associate with endogenous Sost promoter. Taken together, these findings support
      our hypothesis that Sost is a direct target of Osx. This provides a new
      additional mechanism through which Osx inhibits Wnt signaling during bone
      formation.

PMID- 20816667
TI  - Cyclic adenosine monophosphate induces plasminogen activator inhibitor-1
      expression in human mast cells.
AB  - Plaminogen activator inhibitor-1 (PAI-1), the key physiological inhibitor of the
      plasmin fibrinolytic system, plays important roles in the pathogenesis of asthma.
      Mast cells (MCs) are crucial effector cells and a major source of PAI-1 for
      asthma. Cyclic adenosine monophosphate (cAMP) is the important regulator of MCs;
      however, its effects on PAI-1 expression in MCs remain unknown. We reported
      cAMP/protein kinase A pathway positively regulates PAI-1 expression through cAMP
      response element binding protein binding to hypoxia response element-1 at -158 to
      -153bp of human PAI-1 promoter in human MCs. Moreover, cAMP synergistically
      augments PAI-1 expression with ionomycin- or IgE receptor cross-linking-mediated
      stimulation.

PMID- 20816668
TI  - Rosiglitazone induces the unfolded protein response, but has no significant
      effect on cell viability, in monocytic and vascular smooth muscle cells.
AB  - Given the safety concerns expressed over negative cardiovascular outcomes
      resulting from the clinical use of rosiglitazone, and the view that rosiglitazone
      exerts PPARgamma-independent effects alongside its insulin-sensitising PPARgamma
      dependent effects, we hypothesised that rosiglitazone may trigger Unfolded
      Protein Responses (UPRs) due to disruptions in [Ca(2+)](i) homeostasis within two
      cardiovascular cell types: monocytic (MM6) and vascular smooth muscle (A7r5)
      cells. In microsomal samples derived from both cell types, pre-incubation with
      rosiglitazone rapidly (30min) brought about concentration-dependent PPARgamma
      independent inhibition of Ca(2+)ATPase activity (IC(50) ~2MUM). Fluo-3
      fluorimetric data demonstrated in intact cells that 1h treatment with 1 or 10MUM
      rosiglitazone caused Ca(2+) ions to leak into the cytoplasm. Gene expression
      analysis showed that within 4h of rosiglitazone exposure, the UPR transcription
      factor XBP-1 was activated (likely due to corresponding ER Ca(2+) depletion), and
      the UPR target genes BiP and SERCA2b were subsequently upregulated within 24-72h.
      After 72h 1 or 10MUM rosiglitazone treatment, microsomal Ca(2+)ATPase activity
      increased to >2-fold of that seen in control microsomes, while [Ca(2+)](i)
      returned to basal, indicating that UPR-triggered SERCA2b upregulation was
      responsible for enhanced enzymatic Ca(2+) sequestration within the ER. This
      appeared to be sufficient to replenish ER Ca(2+) stores and restore normal cell
      physiology, as cell viability levels were not decreased due to rosiglitazone
      treatment throughout a 2-week study. Thus, incubation with 1-10MUM rosiglitazone
      triggers the UPR, but does not prove cytotoxic, in cells of the cardiovascular
      system. This observation provides an important contribution to the current debate
      over the use of rosiglitazone in the clinical treatment of Type-2 Diabetes.

PMID- 20816669
TI  - MHC class II-associated invariant chain (Ii) modulates dendritic cells-derived
      microvesicles (DCMV)-mediated activation of microglia.
AB  - Dendritic cells (DC) - the sentinels of the immune system - play an important
      role in the maintenance of tolerance and induction of immunity. However, in
      autoimmune diseases, DC initiate the diseases by presenting self antigens to
      autoreactive T cells, causing the immune system to mount a response against the
      body. An example is multiple sclerosis (MS) and its corresponding animal model,
      experimental autoimmune encephalomyelitis (EAE). During inflammation of the
      central nervous system (CNS), DC are recruited to activate autoreactive T cells.
      Microglia - resident mononuclear phagocytes of the brain - also play a role in
      the pathogenesis of the disease. In this study, we demonstrated that
      microvesicles derived from DC (DCMV) induced the activation of NF-kappaB in
      microglia. Furthermore, MHC class II-associated invariant chain (Ii), also known
      as CD74, was specifically recruited to DCMV and interestingly, was able to
      enhance the DCMV-mediated activation of NF-kappaB in microglia. Thus, this study
      emphasizes the role of microvesicles and Ii in the communication between DC and
      microglia.

PMID- 20816670
TI  - A novel approach for stress-induced gastritis based on paradoxical anti-oxidative
      and anti-inflammatory action of exogenous 8-hydroxydeoxyguanosine.
AB  - Reactive oxygen species (ROS) attack guanine bases in DNA and form 8
      hydroxydeoxyguanosine (8-OHdG), which has been regarded simply as an oxidative
      mutagenic by-product. On the other hand, our previous report showed paradoxically
      ROS attenuating action of generated 8-OHdG. In the current study, both in vitro
      and in vivo experiments were executed in order to document anti-oxidative and
      anti-inflammatory actions of 8-OHdG in cell model and to elucidate the
      therapeutic efficacy against water immersion restraint stress (WIRS)-induced
      gastritis animal model. Electron spin resonance measurements showed that 8-OHdG
      at >5MUg/ml completely scavenged OH(-) radicals, which was further confirmed by
      checking 2'-7'-dichlorodihydrofluorescein diacetate (DCFDA) spectroscopy. On
      molecular assay, 8-OHdG antagonized the action of GTP on Rac, a small GTP binding
      protein, without affecting Rac-guanosine exchange factor (GEF) or
      phosphoinositide 3-kinases (PI3K) activity. In Raw264.7 cells, 8-OHdG was found
      to be associated with marked attenuations of NOX1, NOXO1, and NOXA1 accompanied
      with the decreased expressions of LPS-induced inflammatory mediators including
      COX-2, iNOS, IL-1beta, and IL-6. Similarly, 8-OHdG attenuated hypoxia-induced
      angiogenesis and platelet endothelial cell adhesion molecule-1 (PECAM-1), COX-2,
      iNOS, IL-8, and VEGF expressions in HUVEC cells. At transcriptional level, 8-OHdG
      inhibited the nuclear translocation of NF-kappaB, inhibitory kappaB kinase (IKK)
      beta kinase activation, and decreased phospho-IkappaBalpha levels. 8-OHdG
      efficiently ameliorated WIRS-induced gastric mucosal injury as evidenced with
      improvement of gross lesion index and attenuation of engaging mediators. Taken
      together, exogenous 8-OHdG can be a functional molecule regulating oxidative
      stress-induced gastritis through either antagonizing Rac-GTP binding or blocking
      the signals responsible for gastric inflammatory cascade.

PMID- 20816671
TI  - Mechanisms of metformin action on glucose transport and metabolism in human
      adipocytes.
AB  - The mechanisms of metformin effects on glucose transport and metabolism were
      investigated in human adipocytes. Human preadipocytes obtained from surgical
      biopsies were differentiated in vitro into adipocytes and the effects of
      metformin on glucose uptake, glucose oxidation and the involved signaling
      pathways were analyzed. Metformin (1mM, 24h) increased glucose uptake 2.3+/-0.2
      fold (p<0.001 vs. basal) in human adipocytes, without altering cell viability and
      oxygen consumption. Metformin did not alter GLUT-1 mRNA expression and protein
      content but increased GLUT-4 mRNA expression and cellular protein content,
      leading to increased GLUT-4 protein content in the plasma membrane. Neither basal
      nor insulin-induced phosphorylation of Akt at Ser-473 and AS160 (Akt substrate of
      160kDa) at Thr-642 were enhanced by metformin. Suppression of metformin-induced
      AMP-activated protein kinase (AMPK) activity by AMPKalpha1 silencing, however,
      reduced metformin-associated GLUT-4 expression and stimulation of glucose uptake.
      In addition, metformin induced glucose oxidation. In conclusion, activation of
      AMPKalpha1 without impairment of cell respiration is crucial for metformin
      mediated increase in GLUT-4 protein content and glucose uptake in human
      adipocytes.

PMID- 20816672
TI  - Triplex forming oligonucleotides against type alpha1(I) collagen attenuates liver
      fibrosis induced by bile duct ligation.
AB  - Liver fibrosis is a consequence of chronic liver disorders which lead to the
      accumulation of extracellular matrix (ECM). Particularly, there is an increased
      accumulation of collagen in the fibrotic liver. We have therefore used a triplex
      forming oligonucleotide (TFO) against the type alpha1(I) collagen and evaluated,
      whether it can attenuate liver fibrosis induced by common bile duct ligation
      (CBDL) in rats. There was a significant decrease in hydroxyproline levels and
      Masson's trichrome staining for collagen in TFO-treated CBDL groups compared to
      non-treated CBDL group. There was over expression of type alpha1(I) collagen,
      alpha-smooth muscle actin (alpha-SMA) and TGF-beta1 expression in the CBDL group
      compared to TFO-treated CBDL group. Also, the serum alanine transaminase (ALT)
      and aspartate transaminase (AST) concentrations were less in the TFO treated
      group compared to non-treated CBDL group. There was also less neutrophils
      accumulation in TFO treated CBDL group assayed by myeloperoxidase (MPO) assay.
      These results suggests that TFO can be used to downregulate type 1 collagen gene
      expression and can alleviate liver fibrosis induced by common bile duct ligation.

PMID- 20816673
TI  - FGF-2/FGFR1 neurotrophic system expression level and its basal activation do not
      account for the age-dependent decline of precursor cell proliferation in the
      subventricular zone of rat brain.
AB  - It is largely accepted that neurogenesis in the adult brain decreases with age
      and reduced levels of local neurotrophic support is speculated to be a
      contributing factor. Among neurotrophic factors involved on neurogenesis, we
      focused our attention on the neurotrophic system fibroblast growth factor-2 (FGF
      2) and its receptor FGFR1, a potent modulator of precursor cell proliferation. In
      the present work, we aimed to analyse if potential age-dependent changes of the
      FGF-2/FGFR1 neurotrophic system may give account for the age-dependent decline of
      precursor cell proliferation in the neurogenic region of the subventricular zone
      (SVZ) in the rat brain. Using in situ hybridization and western blotting
      procedures we examined FGF-2 and FGFR1 expression levels in the SVZ of 20-month
      old rats as compared to young adult 3-month-old rats. The results showed that
      during aging the FGF-2 and its receptor expression levels, both as mRNA and
      protein, were unchanged in the SVZ. The levels of phosphorylated FGFR1 form did
      not show significant variations suggesting that also the level of receptor
      activation does not change during aging. No changes were also observed in the
      phosphorylation of two FGFR1 related proteins involved in intracellular
      signaling, the canonical extracellular signal-regulated kinase Erk1/2 and the
      phospholipase-Cgamma1. Additionally, we could show that also the proliferation
      rate of stem cells does not change during aging. Taken together, our results show
      that FGF-2/FGFR1 neurotrophic system expression level and its basal activation do
      not account for the age-dependent decline of precursor cell proliferation in the
      rat brain.

PMID- 20816674
TI  - Extracellular hydrogen peroxide contributes to oxidative glutamate toxicity.
AB  - Oxidative glutamate toxicity is characterized by the inhibition of cystine
      uptake, the depletion of intracellular glutathione, and increased levels of
      intracellular reactive oxygen species, factors that lead to neuronal injury. We
      found that the presence of extracellular catalase protected cultured neuronal
      cells, such as HT22, SH-SY5Y and PC12 cells, from glutamate-induced cytotoxicity.
      Extracellular hydrogen peroxide (H2O2) accumulated in a time- and concentration
      dependent manner in HT22 cells during prolonged exposure to glutamate. To
      investigate the involvement of NADPH oxidase in glutamate-induced H2O2
      generation, we used small interference RNA (siRNA). Knockdown of Nox2 and Nox4
      expression reduced H2O2 accumulation and increased cell survival. siRNA specific
      for Nox4 reduced the production of H2O2 by ~74% compared with control siRNA.
      Furthermore, H2O2 accumulation was also suppressed by U0126, a MEK/ERK inhibitor,
      in a concentration-dependent manner. These results suggest that glutamate
      triggers the Nox-dependent generation of extracellular H2O2 via ERK1/2
      activation, which contributes to oxidative glutamate toxicity.

PMID- 20816675
TI  - Area postrema projects to FoxP2 neurons of the pre-locus coeruleus and
      parabrachial nuclei: brainstem sites implicated in sodium appetite regulation.
AB  - The area postrema (AP) is a circumventricular organ located in the dorsal midline
      of the medulla. It functions as a chemosensor for blood-borne peptides and
      solutes, and converts this information into neural signals that are transmitted
      to the nucleus tractus solitarius (NTS) and parabrachial nucleus (PB). One of its
      NTS targets in the rat is the aldosterone-sensitive neurons which contain the
      enzyme 11 beta-hydroxysteroid dehydrogenase type 2 (HSD2). The HSD2 neurons are
      part of a central network involved in sodium appetite regulation, and they
      innervate numerous brain sites including the pre-locus coeruleus (pre-LC) and PB
      external lateral-inner (PBel-inner) cell groups of the dorsolateral pons. Both
      pontine cell groups express the transcription factor FoxP2 and become c-Fos
      activated following sodium depletion. Because the AP is a component in this
      network, we wanted to determine whether it also projects to the same sites as the
      HSD2 neurons. By using a combination of anterograde axonal and retrograde cell
      body tract-tracing techniques in individual rats, we show that the AP projects to
      FoxP2 immunoreactive neurons in the pre-LC and PBel-inner. Thus, the AP sends a
      direct projection to both the first-order medullary (HSD2 neurons of the NTS) and
      the second-order dorsolateral pontine neurons (pre-LC and PB-el inner neurons).
      All three sites transmit information related to systemic sodium depletion to
      forebrain sites and are part of the central neural circuitry that regulates the
      complex behavior of sodium appetite.

PMID- 20816676
TI  - Inhibitory effects of levetiracetam on absence seizures in a novel absence-like
      epilepsy animal model, Groggy rat.
AB  - Levetiracetam (LEV) is known to inhibit convulsive seizures and is clinically
      used for treating both partial and generalized seizures. The study was performed
      to determine whether LEV possesses an inhibitory effect on absence seizures in a
      novel genetic animal model of absence epilepsy, Groggy (GRY) rats. Single
      injections of LEV at doses ranging from 20 to 160 mg/kg i.p. markedly inhibited
      absence seizures in GRY rats. The anti-absence action of LEV was potent and the
      cumulative duration of spike and wave discharges (SWD) in GRY rats was almost
      completely suppressed even at 20 mg/kg (i.p.). When the time-course of the
      inhibitory action of LEV (80 mg/kg i.p.) was examined up to 24 h after the
      treatment, the appearance of SWD was suppressed for over 6 h after injection of
      LEV in contrast to the action of sodium valproate (200 mg/kg i.p.) which had a
      very short effect (< 2 h). The maximum level of blood concentration of LEV was
      attained within 2 h after administration, and the drug disappeared from the blood
      in 24 h with T(1/2) of 2.7 h. These results revealed that LEV displays potent and
      relatively long-lasting inhibitory effects on absence seizures in GRY rats.

PMID- 20816677
TI  - Predictive value of serum apolipoprotein B/LDL-cholesterol ratio in
      cardiometabolic risk: population-based cohort study.
AB  - OBJECTIVES: We determined the independent predictive value of serum
      apolipoprotein (apo) B/LDL-cholesterol ratio for the risk of diabetes, metabolic
      syndrome (MetS) and coronary heart disease (CHD). DESIGN AND METHODS: Prediction
      of incident cases was assessed in 2466 adults at 7 years' follow-up. RESULTS:
      ApoB/LDL ratio was independently associated log-linearly with waist
      circumference, and, only in men, with HDL-cholesterol in a multivariable
      regression model. Positive partial correlations existed with fasting insulin,
      fibrinogen and apo A-I and, only in women, with CRP. Cox regression analyses
      revealed the two highest apoB/LDL quartiles to be significant determinants of
      diabetes, at 2-fold RRs, independently of waist circumference, fasting glucose
      and other confounders. However, apoB/LDL quartiles were not independently
      associated with CHD in either gender. Only the highest apoB/LDL quartile was
      associated (RR 1.46) with the development of MetS. Serum apoB/LDL-cholesterol
      ratio, determined by insulin resistance and in women additionally by pro
      inflammatory state, is of independent predictive value for incident diabetes and
      weakly for MetS, but not for CHD.

PMID- 20816679
TI  - Acrosome reaction-related steroidal saponin, Co-ARIS, from the starfish induces
      structural changes in microdomains.
AB  - Cofactor for acrosome reaction-inducing substance (Co-ARIS) is a steroidal
      saponin from the starfish Asterias amurensis. Saponins exist in many plants and
      few animals as self-defensive chemicals, but Co-ARIS has been identified as a
      cofactor for inducing the acrosome reaction (AR). In A. amurensis, the AR is
      induced by the cooperative action of egg coat components (ARIS, Co-ARIS, and
      asterosap); however, the mechanism of action of Co-ARIS is obscure. In this study
      we elucidated the membrane dynamics involved in the action of Co-ARIS. We found
      that cholesterol specifically inhibited the Co-ARIS activity for AR induction and
      detected the binding of labeled compounds with sperm using radioisotope-labeled
      Co-ARIS. Co-ARIS treatment did not reduce the content of sperm sterols, however,
      the condition was changed and localization of GM1 ganglioside on the
      periacrosomal region disappeared. We then developed a caveola-breaking assay, a
      novel method to detect the effect of chemicals on microdomains of culture cell,
      and confirmed the disturbance of somatic cell caveolae in the presence of Co
      ARIS. Finally, by atomic force microscopy observations and surface plasmon
      resonance measurements using an artificial membrane, we revealed that Co-ARIS
      colocalized with GM1 clusters on the microdomains. Through this study, we
      revealed a capacitation-like event for AR in starfish sperm.

PMID- 20816678
TI  - The Drosophila gap gene giant regulates ecdysone production through specification
      of the PTTH-producing neurons.
AB  - In Drosophila melanogaster, hypomorphic mutations in the gap gene giant (gt) have
      long been known to affect ecdysone titers resulting in developmental delay and
      the production of large (giant) larvae, pupae and adults. However, the mechanism
      by which gt regulates ecdysone production has remained elusive. Here we show that
      hypomorphic gt mutations lead to ecdysone deficiency and developmental delay by
      affecting the specification of the PG neurons that produce prothoracicotropic
      hormone (PTTH). The gt1 hypomorphic mutation leads to random loss of PTTH
      production in one or more of the 4 PG neurons in the larval brain. In cases where
      PTTH production is lost in all four PG neurons, delayed development and giant
      larvae are produced. Since immunostaining shows no evidence for Gt expression in
      the PG neurons once PTTH production is detectable, it is unlikely that Gt
      directly regulates PTTH expression. Instead, we find that innervation of the
      prothoracic gland by the PG neurons is absent in gt hypomorphic larvae that do
      not express PTTH. In addition, PG neuron axon fasciculation is abnormal in many
      gt hypomorphic larvae. Since several other anteriorly expressed gap genes such as
      tailless and orthodenticle have previously been found to affect the fate of the
      cerebral labrum, a region of the brain that gives rise to the neuroendocrine
      cells that innervate the ring gland, we conclude that gt likely controls ecdysone
      production indirectly by contributing the peptidergic phenotype of the PTTH
      producing neurons in the embryo.

PMID- 20816680
TI  - Differential gene expression profiling of cultured neu-transformed versus
      spontaneously-transformed rat cholangiocytes and of corresponding
      cholangiocarcinomas.
AB  - Previously, we described an orthotopic cholangiocarcinoma model based on bile
      duct inoculation of spontaneously-transformed low grade malignant rat BDE1
      cholangiocytes (BDEsp cells) compared to high grade malignant erbB-2/neu-
      transformed BDE1 cholangiocytes (BDEneu cells) into the livers of syngeneic rats,
      which closely mimics clinical features of early versus advanced stages of the
      human cancer. We now used gene expression microarray together with quantitative
      real-time RT-PCR to profile genes differentially expressed in highly tumorigenic
      BDEneu cells and corresponding tumors compared to less aggressive tumorigenic
      BDEsp cells and tumors. Genes identified as being commonly overexpressed in
      parent BDEneu cells, tumors, and in a BDEneu tumor-derived cholangiocarcinoma
      cell line included Sox17, Krt20, Erbb2, and Sphk1 when respectively compared to
      BDEsp cells, tumors, and tumor-derived BDEsp cholangiocarcinoma cells. Muc1 was
      also prominently overexpressed in BDEneu cells and tumor-derived
      cholangiocarcinoma cells over that expressed in corresponding BDEsp cell lines.
      Periostin and tenascin-C, which were produced exclusively by cholangiocarcinoma
      associated fibroblastic cells, were each significantly overexpressed in BDEneu
      tumors compared to BDEsp tumors. Interestingly, amphiregulin was representative
      of a gene found to be significantly underexpressed in vitro in BDEneu cells
      compared to BDEsp cells, but significantly overexpressed in BDEneu tumors
      compared to BDEsp tumors, and correlated with BDEneu cholangiocarcinoma
      progression in vivo. Our data support a unique animal model that recapitulates
      important molecular features of human cholangiocarcinoma progression, and may
      serve as a potentially powerful preclinical platform for identifying and rapidly
      testing novel molecular targeting strategies for cholangiocarcinoma therapy
      and/or prevention.

PMID- 20816682
TI  - A spatial model of cellular molecular trafficking including active transport
      along microtubules.
AB  - We consider models of Ran-driven nuclear transport of molecules such as proteins
      in living cells. The mathematical model presented is the first to take into
      account for the active transport of molecules along the cytoplasmic microtubules.
      All parameters entering the models are thoroughly discussed. The model is tested
      by numerical simulations based on discontinuous Galerkin finite element methods.
      The numerical experiments are compared to the behavior observed experimentally.

PMID- 20816681
TI  - Analysis of molecular markers for metamorphic competency and their response to
      starvation or feeding in the mosquito, Aedes aegypti (Diptera: Culicidae).
AB  - The nutritional condition of fourth instar larvae of the yellow fever mosquito,
      Aedes aegypti, governs female longevity and egg production, both are key
      determinants of pathogen transmission. As well, nutrition provisions larval
      growth and development and attains its greatest pace in the last larval instar in
      preparation for metamorphosis to an adult. These developmental processes are
      regulated by a complex endocrine interplay of juvenile hormone, neuropeptides,
      and ecdysteroids that is nutrition sensitive. We previously determined that
      feeding for only 24h post-ecdysis was sufficient for fourth instar Ae. aegypti
      larvae to reach critical weight and accumulate sufficient nutritional stores to
      commit to metamorphosis. To understand the genetic basis of metamorphic
      commitment in Ae. aegypti, we profiled the expression of 16 genes known to be
      involved in the endocrine and nutritional regulation of insect metamorphosis in
      two ways. The first set is a developmental profile from the beginning of the
      fourth instar to early pupae, and the second set is for fourth instars starved or
      fed for up to 36 h. By comparing the two sets, we found that seven of the genes
      (AaegCYP302, AaegJHE43357, AaegBrCZ4, AaegCPF1-2, AaegCPR-7, AaegPpl, and
      AaegSlif) were expressed during metamorphic commitment in fourth instars and in
      fed but not starved larvae. Based on these results, the seven genes alone or in
      combination may serve as molecular indicators of nutritional and metamorphic
      status of fourth instar Ae. aegypti larvae and possibly other mosquito species in
      field and laboratory studies to gauge sub-lethal effects of novel and traditional
      cultural or chemical controls.

PMID- 20816683
TI  - Cascading extinctions, functional complementarity, and selection in two-trophic
      level model communities: a trait-based mechanistic approach.
AB  - The influence of diversity on ecosystem functioning and ecosystem services is now
      well established. Yet predictive mechanistic models that link species traits and
      community-level processes remain scarce, particularly for multitrophic systems.
      Here we revisit MacArthur's classical consumer resource model and develop a trait
      based approach to predict the effects of consumer diversity on cascading
      extinctions and aggregated ecosystem processes in a two-trophic-level system. We
      show that functionally redundant efficient consumers generate top-down cascading
      extinctions. This counterintuitive result reveals the limits of the functional
      redundancy concept to predict the consequences of species deletion. Our model
      also predicts that the biodiversity-ecosystem functioning relationship is
      different for different ecosystem processes and depends on the range of variation
      of consumer traits in the regional species pool, which determines the sign of
      selection effects. Lastly, competition among resources and consumer generalism
      both weaken complementarity effects, which suggests that selection effects may
      prevail at higher trophic levels. Our work emphasizes the potential of trait
      based approaches for transforming biodiversity and ecosystem functioning research
      into a more predictive science.

PMID- 20816685
TI  - Scaling of lunge feeding in rorqual whales: an integrated model of engulfment
      duration.
AB  - Rorqual whales (Balaenopteridae) obtain their food by lunge feeding, a dynamic
      process that involves the intermittent engulfment and filtering of large amounts
      of water and prey. During a lunge, whales accelerate to high speed and open their
      mouth wide, thereby exposing a highly distensible buccal cavity to the flow and
      facilitating its inflation. Unsteady hydrodynamic models suggest that the muscles
      associated with the ventral groove blubber undergo eccentric contraction in order
      to stiffen and control the inflation of the buccal cavity; in doing so the
      engulfed water mass is accelerated forward as the whale's body slows down.
      Although the basic mechanics of lunge feeding are relatively well known, the
      scaling of this process remains poorly understood, particularly with regards to
      its duration (from mouth opening to closure). Here we formulate a new theory of
      engulfment time which integrates prey escape behavior with the mechanics of the
      whale's body, including lunge speed and acceleration, gape angle dynamics, and
      the controlled inflation of the buccal cavity. Given that the complex interaction
      between these factors must be highly coordinated in order to maximize engulfment
      volume, the proposed formulation rests on the scenario of Synchronized
      Engulfment, whereby the filling of the cavity (posterior to the temporomandibular
      joint) coincides with the moment of maximum gape. When formulated specifically
      for large rorquals feeding on krill, our analysis predicts that engulfment time
      increases with body size, but in amounts dictated by the specifics of krill
      escape and avoidance kinematics. The predictions generated by the model are
      corroborated by limited empirical data on a species-specific basis, particularly
      for humpback and blue whales chasing krill. A sensitivity analysis applied to all
      possible sized fin whales also suggests that engulfment duration and lunge speed
      will increase intra-specifically with body size under a wide range of predator
      prey scenarios. This study provides the theoretical framework required to
      estimate the scaling of the mass-specific drag being generated during engulfment,
      as well as the energy expenditures incurred.

PMID- 20816686
TI  - Random discrete competing events vs. dynamic bistable switches in cell
      proliferation in differentiation.
AB  - Several recent experiments related to fundamental aspects of cell behaviour, such
      as passing of the restriction point of cell cycle, which are generally
      interpreted in accordance with the dynamic paradigm implying the use of
      differential equations operating with the concentrations of cellular components
      and rate constants of their interactions, are shown in the present paper to be
      consistent with a simple model based on discrete competing stochastic events
      interpreted as assembly of alternative complexes of transcription factors at gene
      promoters. The model conforms to the transition probability model of cell cycle
      and to the stochastic approaches to cell differentiation and integrates them with
      the restriction point concept.

PMID- 20816684
TI  - Tumour-stromal interactions in acid-mediated invasion: a mathematical model.
AB  - It is well established that the tumour microenvironment can both promote and
      suppress tumour growth and invasion, however, most mathematical models of
      invasion view the normal tissue as inhibiting tumour progression via immune
      modulation or spatial constraint. In particular, the production of acid by tumour
      cells and the subsequent creation of a low extracellular pH environment has been
      explored in several 'acid-mediated tumour invasion' models where the acidic
      environment facilitates normal cell death and permits tumour invasion. In this
      paper, we extend the acid-invasion model developed by Gatenby and Gawlinski
      (1996) to include both the competitive and cooperative interactions between
      tumour and normal cells, by incorporating the influence of extracellular matrix
      and protease production at the tumour-stroma interface. Our model predicts an
      optimal level of tumour acidity which produces both cell death and matrix
      degradation. Additionally, very aggressive tumours prevent protease production
      and matrix degradation by excessive normal cell destruction, leading to an
      acellular (but matrix filled) gap between the tumour and normal tissue, a feature
      seen in encapsulated tumours. These results suggest, counterintuitively, that
      increasing tumour acidity may, in some cases, prevent tumour invasion.

PMID- 20816687
TI  - Accuracy of calculated free testosterone differs between equations and depends on
      gender and SHBG concentration.
AB  - Serum free testosterone (fT) concentrations are often calculated, however
      different equations often yield discrepant results. This study explores the
      sources of this variability. We compared three established and two new equations
      that differed only by their testosterone association constants with isotope
      dilution equilibrium dialysis in two patient groups with different gender
      distributions. Equation components were examined to determine how they impacted
      correlation with isotope dilution equilibrium dialysis. Association constants
      derived for each patient group correlated best with isotope dilution equilibrium
      dialysis for that group and not the other set. Samples with the poorest
      correlation between isotope dilution equilibrium dialysis and calculated fT
      results had significantly higher SHBG concentrations. Regardless of equation, >=
      25% of samples showed unacceptable deviation from isotope dilution equilibrium
      dialysis. Association constants and gender makeup and SHBG concentration of the
      patient groups used to establish an equation all significantly impact correlation
      with isotope dilution equilibrium dialysis. Application of many fT equations to
      wider populations will therefore frequently yield results that differ
      substantially from isotope dilution equilibrium dialysis.

PMID- 20816688
TI  - Distribution and responsiveness of rat anti-Mullerian hormone during ovarian
      development and VCD-induced ovotoxicity.
AB  - Anti-Mullerian hormone (AMH) is produced by granulosa cells in primary to small
      antral follicles of the adult ovary and helps maintain primordial follicles in a
      dormant state. The industrial chemical, 4-vinylcyclohexene diepoxide (VCD) causes
      specific ovotoxicity in primordial and small primary follicles of mice and rats.
      Previous studies suggest that this ovotoxicity involves acceleration of
      primordial to primary follicle recruitment via interactions with the Kit/Kit
      ligand signaling pathway. Because of its accepted role in inhibiting primordial
      follicle recruitment, the present study was designed to investigate a possible
      interaction between AMH and VCD-induced ovotoxicity. Protein distribution of AMH
      was compared in neonatal and adult F344 rat ovaries. AMH protein was visualized
      by immunofluorescence microscopy in large primary and secondary follicles of the
      adult ovary, but in small primary follicles in neonatal rat ovaries. In cultured
      postnatal day (PND) 4 F344 rat ovaries, VCD exposure (30 MUM, 2-8 days) decreased
      (P<0.05) AMH mRNA (d4-8) and protein (d6-8). Recombinant AMH (100-400 mg/ml) in
      PND4 ovaries cultured 8 days+/-VCD (30 MUM) caused an increase (P<0.05) in
      primordial, and a decrease (P<0.05) in small primary follicles, supporting that
      AMH retarded primordial follicle recruitment. However, no concentration of AMH
      had an effect on VCD-induced ovotoxicity. Whereas, VCD caused a reduction in
      expression of AMH (d4-d8), it followed previously reported initial disruptions in
      Kit signaling induced by VCD (d2). Thus, collectively, these results do not
      support a mechanism whereby VCD causes ovotoxicity via generalized activation of
      primordial follicle recruitment, but instead provide further support for the
      specificity of other intracellular mechanisms involved in VCD-induced
      ovotoxicity.

PMID- 20816689
TI  - Isolation and characterization of a novel two-component hemolysin, erylysin A and
      B, from an edible mushroom, Pleurotus eryngii.
AB  - A novel two-component hemolysin, erylysin A and B (EryA and EryB), was isolated
      from an edible mushroom, Pleurotus eryngii. Hemolytic activity was exhibited only
      by the EryA and EryB mixture. EryA showed one band at 15 kDa on SDS-PAGE while
      EryB showed two bands at 15 kDa (EryB1) and 37 kDa (EryB2). MALDI-TOF MS showed
      that the molecular masses of EryA, EryB1 and EryB2 were 14,945 Da, 14,593 Da and
      37,417 Da, respectively. EryA and EryB were very similar to pleurotolysin A and B
      in terms of molecular mass, and the N-terminus and inner sequences. At pH 7.2,
      EryA exists as a homodimer whereas EryB exists as a heterodimer of B1 and B2. CD
      spectrum analysis showed T(m) values of 47  degrees C and 37  degrees C for EryA
      and EryB, respectively. EryB was particularly unstable.

PMID- 20816690
TI  - Changes in gene expression associated with aging commonly originate during
      juvenile growth.
AB  - In mammals, proliferation is rapid in many tissues during early postnatal life,
      causing rapid somatic growth. This robust proliferation is then suppressed as the
      animal approaches adult size, bringing many tissues to a quiescent state where
      proliferation occurs only as needed to replace dying cells. Recent evidence
      suggests that the mechanism responsible for this decline in proliferation
      involves a multi-organ genetic program. We hypothesized that this genetic program
      continues to progress into later adult life, eventually suppressing proliferation
      to levels below those needed for tissue renewal, thus contributing to aging. We
      therefore used expression microarray to compare the temporal changes in gene
      expression that occur in adult mouse organs during aging to those occurring as
      juvenile proliferation slows. We found that many of the changes in gene
      expression that occur during the aging process originate during the period of
      juvenile growth deceleration. Bioinformatic analyses of the genes that show
      persistent decline in expression throughout postnatal life indicated that cell
      cycle-related genes are strongly over-represented. Thus, the findings support the
      hypothesis that the genetic program that slows juvenile growth to limit body size
      persists into adulthood and thus may eventually hamper tissue maintenance and
      repair, contributing to the aging process.

PMID- 20816691
TI  - A functional single nucleotide polymorphism in promoter of ATM is associated with
      longevity.
AB  - Although the 'ataxia telangiectasia mutated' (ATM) gene plays an important role
      in physiological processes, such as sensing DNA damage, reducing oxidative stress
      and protecting telomeres length, little information about ATM and longevity is
      available. Therefore, we aim to examine the association between genetic variants
      in promoter of ATM and longevity in Chinese Nonagenarians/Centenarians.
      Genotyping was performed in 789 long-lived individuals (LLIs) and 886 ethnically
      matched control subjects. A single nucleotide polymorphism (SNP, rs189037) in the
      promoter region of ATM gene was identified, and significant association between
      CT genotype and longevity was observed. Meanwhile, the SNP was able to affect
      expression of ATM mRNA by differentially binding to AP-2alpha. The CC genotype
      strongly bound to AP-2alpha, and the TT genotype showed less binding affinity to
      AP-2alpha. The AP-2alpha strongly repressed the reporter expression in the CC
      genotype and showed less repression of the TT genotype driving expression in
      vitro assay. Accordingly, TT genotype individuals had highest ATM mRNA
      expression, CT genotype individuals had moderate ATM mRNA expression, and the CC
      genotype individuals had the lowest ATM mRNA.

PMID- 20816692
TI  - Comparison of ex vivo and in vitro human fibroblast ageing models.
AB  - Several studies have analyzed modulation of gene expression during physiological
      ageing with interesting, but often contradictory results, depending on the model
      used. In the present report we compare age-related metabolic and synthetic
      parameters in human dermal fibroblasts (HDF) isolated from young and old subjects
      (ex vivo ageing model) and cultured from early up to late cumulative population
      doublings (CPD) (in vitro ageing model) in order to distinguish changes induced
      in vivo by the aged environment and maintained in vitro, from those associated
      with cell senescence and progressive CPD. Results demonstrate that fibroblasts
      from aged donors, already at early CPD, exhibit an impaired redox balance,
      highlighting the importance of this parameter during ageing, even in the presence
      of standard environmental conditions, which are considered optimal for cell
      growth. By contrast, several proteins, as those related to heat shock response,
      or involved in endoplasmic reticulum and membrane trafficking, appeared
      differentially expressed only during in vitro ageing, suggesting that, at high
      CPD, the whole cell machinery becomes permanently altered. Finally, given the
      importance of the elastic component for a long-lasting connective tissue
      structural and functional compliance, this study focuses also on elastin and
      fibulin-5 synthesis and deposition, demonstrating a close relationship between
      fibulin-5 and ageing.

PMID- 20816693
TI  - Utility of accelerometer thresholds for classifying sitting in office workers.
AB  - OBJECTIVE: To investigate the utility of a variety of Actical accelerometer count
      thresholds for determining sitting time in a sample of office workers. METHODS:
      Data were collected from 21 participants in Auckland, New Zealand, between
      December 2009 and January 2010. Participants wore a hip-mounted Actical
      accelerometer and thigh-mounted activPAL inclinometer (criterion) for a 48-h
      period. Raw inclinometer and accelerometer data for each 15s epoch of wear time
      were matched by date and time. Candidate accelerometer count thresholds for
      sitting classification were compared with the criterion measure using receiver
      operating characteristic analyses. Agreement in sitting time classification was
      determined using Bland-Altman methodology. RESULTS: Significant differences in
      area under the curve (AUC) values by threshold criteria were found (p<0.001). A
      threshold of 0 counts provided the highest combined sensitivity and specificity
      (AUC 0.759, 95%CI 0.756, 0.761). The 95% limits of agreement for time spent
      sitting were wide, at 328min (range -30.8, 297.5). CONCLUSION: A threshold of 0
      counts/15s epoch with Actical accelerometers is likely to yield the most accurate
      quantification of sitting in office-based workers, however the wide limits of
      agreement found indicate limited utility of this threshold to accurately
      distinguish sitting time in office-based workers.

PMID- 20816694
TI  - The two suborders of chiropterans have the canonical heavy-chain immunoglobulin
      (Ig) gene repertoire of eutherian mammals.
AB  - Bats comprise 20% of all mammals, yet little is known about their immune system
      and virtually nothing about their immunoglobulin genes. We show that four
      different bat species transcribe genes encoding IgM, IgE, IgA and IgG subclasses,
      the latter which have diversified after speciation; the canonical pattern for
      eutherian mammals. IgD transcripts were only recovered from insectivorous bats
      and were comprised of CH1, CH3 and two hinge exons; the second hinge exon was
      fused to CH3. IgA in all species resembles human IgA2 with the putative cysteine
      forming the bridge to the light chain found at position 77. Sequence comparisons
      yielded no evidence for a diphyletic origin of the suborders. Bats show no close
      similarity to another mammalian order; the strongest association was with
      carnivores. Data reveal that CH diversity and VDJ and CDR3 organization are
      similar to other eutherian mammals, although the expressed VH3 family repertoire
      was unusually diverse.

PMID- 20816695
TI  - Pandemic influenza A(H1N1) 2009 and respiratory syncytial virus associated
      hospitalizations.
AB  - OBJECTIVES: To determine the contribution of influenza and respiratory syncytial
      virus (RSV) as the cause of lower respiratory tract infection (LRTI) associated
      hospitalizations during the first year of the influenza A(H1N1) 2009 pandemic and
      to assess the severity of illness during the second pandemic wave. METHODS:
      Patients admitted with LRTI from April 2009 through March 2010 were assessed for
      the presence of influenza and RSV. Pandemic influenza virus was detected by means
      of a nested RT-PCR assay and/or the CDC's real time-PCR protocol. RSV was
      detected using a one-step RT-PCR assay. The characteristics of patients admitted
      during the first and second pandemic outbreaks were compared. RESULTS: 657
      patients with LRTI were admitted during the study period. Pandemic influenza
      virus was detected in 180 and RSV in 133. Influenza was the most common cause of
      infection in adults, while RSV was more common in children. There were no
      differences in disease severity between the first and second pandemic outbreaks.
      CONCLUSIONS: Pandemic influenza virus was associated to increased numbers of
      hospitalizations and deaths; particularly in adults. The severity of the first
      and second pandemic outbreaks was similar. RSV continues to be the main pathogen
      responsible for hospitalizations in young children.

PMID- 20816696
TI  - HIV-1 matrix protein p17: a candidate antigen for therapeutic vaccines against
      AIDS.
AB  - The success in the development of anti-retroviral therapies (HAART) that contain
      human immunodeficiency virus type 1 (HIV-1) infection is challenged by the cost
      of this lifelong therapy and by its toxicity. Immune-based therapeutic strategies
      that boost the immune response against HIV-1 proteins or protein subunits have
      been recently proposed to control virus replication in order to provide
      protection from disease development, reduce virus transmission, and help limit
      the use of anti-retroviral treatments. HIV-1 matrix protein p17 is a structural
      protein that is critically involved in most stages of the life cycle of the
      retrovirus. Besides its well established role in the virus life cycle, increasing
      evidence suggests that p17 may also be active extracellularly in deregulating
      biological activities of many different immune cells that are directly or
      indirectly involved in AIDS pathogenesis. Thus, p17 might represent a promising
      target for developing a therapeutic vaccine as a contribution to combating AIDS.
      In this article we review the biological characteristics of HIV-1 matrix protein
      p17 and we describe why a synthetic peptide representative of the p17 functional
      epitope may work as a vaccine molecule capable of inducing anti-p17 neutralizing
      response against p17 derived from divergent HIV-1 strains.

PMID- 20816697
TI  - Detergent fraction of heterologous antigen to detect IgA and IgG in
      strongyloidiasis using saliva and serum paired samples.
AB  - Strongyloides stercoralis causes chronic asymptomatic infections in
      immunocompetent human hosts and systemic invasion in immunocompromised patients,
      developing into a fatal hyperinfection syndrome. IgA and IgG detection in saliva
      and serum paired samples were tested using total saline extract from
      Strongyloides venezuelensis (SE(*)) and its detergent phase (D) extracted with
      Triton X-114. Saliva and serum paired samples were obtained from: 25 patients
      with confirmed strongyloidiasis; 25 patients with other parasitoses and 20 from
      apparently healthy individuals. Sensitivity, specificity, diagnostic efficiency,
      positive and negative predictive values and likelihood ratio were calculated at
      the optimum point of reaction. Using D phase sensitivity and specificity to
      detect IgA in saliva were 76.0% and 88.9% and in serum 80.0% and 86.7%,
      respectively. To detect IgG, D phase showed sensitivity and specificity of 88.0%
      and 88.9% in saliva and 88.0% and 84.4% in serum, respectively. D phase proved to
      be specific and efficient and could be utilized as an alternative antigen for IgA
      and IgG detection in saliva and serum samples for strongyloidiasis diagnosis.

PMID- 20816698
TI  - Prevalence of BPV genotypes in a German cowshed determined by a novel multiplex
      BPV genotyping assay.
AB  - Bovine papillomaviruses (BPV) induce benign tumours of the cutaneous or mucosal
      epithelia in cattle, but are also involved in the development of cancer of the
      urinary bladder and of the upper gastrointestinal tract. Current BPV genotyping
      assays employ techniques developed originally for the detection of human
      papillomaviruses. These methods rely on consensus PCR amplification and
      subsequent sequencing and are cumbersome and limited in their analytic
      sensitivity to detect BPV, especially in multiple infections. In this study, a
      novel multiplex BPV genotyping assay is described to detect sensitively and
      specifically BPV-1 to -10 as well as BaPV-11. The assay is based on a multiplex
      PCR using novel broad-spectrum bovine papillomavirus (BSBP) primers followed by
      multiplex bovine genotyping (MBG) by Luminex xMAP technology. The detection limit
      of the assay was shown to be between 10 and 100 BPV genomes. In a first
      application, BPV was detected in 100% of wart preparations with BPV-8 being most
      prevalent, followed by types 6, 1 and 10. The majority of warts were positive for
      at least four BPV types. In conclusion, BSBP-PCR/MBG is a powerful high
      throughput method suitable for the study of the natural history of BPV and could
      be useful to veterinarians for the monitoring of the efficacy of future BPV
      vaccines.

PMID- 20816699
TI  - Quantitation of HTLV-I proviral load by a real-time PCR assay using SYBR Green:
      comparison of two methods for DNA isolation.
AB  - A real-time quantitative PCR (qPCR) assay using SYBR Green was developed to
      determine HTLV-I proviral load (pVL) in peripheral blood mononuclear cells
      (PBMCs), and its performance was evaluated with samples processed as cell lysates
      and DNA isolated by salting out. Primers targeting the pol region were
      standardized against the MT2 cell line and HTLV-I copy number was normalized to
      the amount of cellular DNA by quantitation of the albumin gene. The sensitivity,
      specificity and reproducibility of the qPCR were assessed in the two methods used
      for DNA processing. The assay had a limit of detection of 400 HTLV-I copies/10(6)
      PBMCs for both methods, with a broad range of quantitation (2.6log(10) to
      >5log(10)), and without cross-reactivity with HTLV-II or with HIV-1. The inter-
      and intra-assay coefficients of variation were less than 2.4%. HTLV-I pVL
      quantitation in seven blood donor samples processed as either cell lysates or
      isolated DNA by salting out showed a strong linear correlation and no difference
      in the calculated pVL (Fisher's exact test, p>0.05). The assay was found to be a
      low cost, robust and reproducible assay for quantifying HTLV-I pVL in samples
      processed as cell lysates or as isolated DNA.

PMID- 20816700
TI  - Amantadine resistance in relation to the evolution of influenza A(H3N2) viruses
      in Iran.
AB  - The aminoadamantanes, amantadine and rimantadine, have been used to prevent and
      treat influenza A virus infections for many years. Several reports have shown an
      increased level of resistance to these drugs, particularly among influenza
      A(H3N2) subtype viruses, during recent years. We observed an increase in
      amantadine resistance, due to a Ser31Asn mutation in the M2 channel protein,
      among A(H3N2) viruses circulating in Iran during 2005-2007. Sequence analyses of
      the haemagglutinin and neuraminidase genes as well as the M gene of these viruses
      revealed that the emergence of resistance was in general consistent with the
      progressive worldwide evolution of H3N2 viruses.

PMID- 20816701
TI  - General and social anxiety in the BTBR T+ tf/J mouse strain.
AB  - BTBR T+ tf/J (BTBR) is an inbred mouse strain that shows behavioral traits with
      analogies to the three diagnostic symptoms of autism spectrum disorder (ASD);
      deficits in social interaction, impaired communication, and repetitive behaviors
      with restricted interests. Previous findings reveal that when compared to
      C57BL/6J (B6) and other inbred strains, BTBR exhibit normal to low anxiety-like
      traits in paradigms designed to assess anxiety-related behaviors. The current
      study assessed the generality of these anxiety findings. In experiment 1, B6 and
      BTBR mice were tested in the elevated plus maze (EPM), mouse defense test battery
      (MDTB) and elevated zero-maze. BTBR mice exhibited an anxiogenic profile in the
      EPM, with a reduction in open arm time and an increase in risk assessment
      behaviors, as compared to B6. In the MDTB, BTBR showed enhanced vocalization to
      the predator, and significantly less locomotor activity than B6 in the pre-threat
      situation, but significantly more locomotion than B6 following exposure to a
      predator threat, suggesting enhanced defensiveness to the predator. In the zero
      maze, BTBR mice showed a significantly higher number of entries and time spent in
      the open segments of the apparatus, when compared to B6. In experiment 2, a three
      chambered social preference test was used to evaluate effects of the systemic
      administration of an anxiolytic compound, diazepam, on B6 and BTBR social
      approach. Diazepam consistently increased time in the compartment containing the
      social stimulus, for both B6 and BTBR mice. However, in the vehicle treated
      groups, B6 mice spent significantly more time while BTBR mice spent significantly
      less time in the social stimulus compartment; after diazepam administration both
      B6 and BTBR strains significantly preferred the social stimulus chamber. These
      results suggest that while the anxiety responses of BTBR mice to novel situations
      (EPM and zero-maze) are inconsistent, BTBR mice appear to be more defensive to
      animate threat stimuli (predator or another mouse). Reduction of anxiety by
      diazepam normalized the social preference of BTBR for a mouse stimulus in the
      three-chambered test.

PMID- 20816702
TI  - Associative cortico-cortical plasticity may affect ipsilateral finger opposition
      movements.
AB  - We have recently demonstrated that cortico-cortical paired associative
      stimulation (cc-PAS) can modulate interhemispheric inhibition (IHI) in the human
      brain. Here we further explored the after effects of cc-PAS on fine hand
      movements. Ten healthy right-handed volunteers received 90 paired transcranial
      stimuli to the right and left primary motor hand area (M1(HAND)) at an
      interstimulus interval (ISI) of 8 ms. We studied the after effects of cc-PAS on
      the performance of repetitive finger opposition movements of different complexity
      on both hands using a sensor-engineered glove. A quantitative evaluation of the
      following parameters was performed: Touch Duration (TD), Inter Tapping Interval
      (ITI) and Number of Errors (NE). We confirmed previous data by showing that left
      to-right and right-to-left cc-PAS attenuated IHI. The new finding is that both
      left-to-right and right-to-left cc-PAS were able to influence the performance of
      a simple finger opposition movement changing the duration of TD and ITI.
      Interestingly the effect on the two hands was opposite in direction. These
      results provide further insight that cc-PAS can induce associative plasticity in
      connections between the targeted cortical areas influencing motor hand
      performances. These results may be relevant for future rehabilitative
      applications.

PMID- 20816703
TI  - Maternal separation decreases adult hippocampal cell proliferation and impairs
      cognitive performance but has little effect on stress sensitivity and anxiety in
      adult Wistar rats.
AB  - Stressful events during childhood are thought to increase the risk for the
      development of adult psychopathology. A widely used animal model for early life
      stress is maternal separation (MS), which is thought to affect development and
      cause alterations in neuroendocrine stress reactivity and emotionality lasting
      into adulthood. However, results obtained with this paradigm are inconsistent.
      Here we investigated whether this variation may be related to the type of
      stressor or the tests used to assess adult stress sensitivity and behavioral
      performance. Rat pups were exposed to a 3h daily MS protocol during postnatal
      weeks 1-2. In adulthood, animals were subjected to a wide variety of stressors
      and tests to obtain a better view on the effects of MS on adult hypothalamic
      pituitary-adrenal (HPA) axis regulation, anxiety-like behavior, social
      interaction and cognition. Also, the influence of MS on adult hippocampal
      neurogenesis was studied because it might underlie changes in neuroendocrine
      regulation and behavioral performance. The results show that, independent of the
      nature of the stressor, MS did not affect the neuroendocrine response. MS did not
      influence anxiety-like behavior, explorative behavior and social interaction, but
      did affect cognitive function in an object recognition task. The amount of new
      born cells in the hippocampal dentate gyrus was significantly decreased in MS
      animals; yet, cell differentiation and survival were not altered. In conclusion,
      while interfering with the mother-infant relationship early in life did affect
      some aspects of adult neuroplasticity and cognitive function, it did not lead to
      permanent changes in stress sensitivity and emotionality.

PMID- 20816704
TI  - Survivin signaling is regulated through nuclear factor-kappa B pathway during
      glycochenodeoxycholate-induced hepatocyte apoptosis.
AB  - Hepatocytes in primary culture undergo apoptosis upon exposure to
      glycochenodeoxycholate (GCDC). The signaling mechanisms of GCDC-induced apoptosis
      remain unclear. To investigate the role of antiapoptotic genes, we compared
      apoptotic response in primary hepatocytes following GCDC treatment. The
      hepatocytes from adult Sprague-Dawley rats were cultured in collagen-coated
      dishes and treated with GCDC in varying concentrations, or the same concentration
      at different time intervals. Apoptosis was detected by the terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, DNA
      fragmentation assay, and caspase assays. Expression of apoptosis-related genes
      and proteins was evaluated by RT-PCR, quantitative real-time PCR (qRT-PCR), and
      Western blotting, respectively. The DNA-binding property of a nuclear protein was
      assessed by electrophoretic mobility shift assay (EMSA) and chromatin
      immunoprecipitation (ChIP) assay. An interesting result was that GCDC caused
      hepatocyte apoptosis to display a biphasic phenomenon at a dosage of 50MUM,
      whereas it was not found at higher dosages such as 200MUM. GCDC stimulated the
      expression of antiapoptotic Survivin, which also presented a biphasic response.
      The activation of nuclear factor-kappaB (NF-kappaB) corresponded with the up
      regulation of Survivin. The inhibitor of NF-kappaB, BAY 11-7082, suppressed the
      expression of Survivin and simultaneously eliminated the biphasic response. The
      expression of Survivin was transcriptionally mediated by the activation of NF
      kappaB, as shown by EMSA and ChIP assay. CONCLUSIONS: These results demonstrated
      that a low dosage of GCDC induced the hepatocyte apoptosis to exhibit the
      biphasic response, which was regulated by the expression of Survivin through NF
      kappaB signaling pathway.

PMID- 20816706
TI  - In vitro and in vivo model systems to study microbial biofilm formation.
AB  - Biofilm formation is often considered the underlying reason why treatment with an
      antimicrobial agent fails and as an estimated 65-80% of all human infections is
      thought to be biofilm-related, this presents a serious challenge. Biofilm model
      systems are essential to gain a better understanding of the mechanisms involved
      in biofilm formation and resistance. In this review a comprehensive overview of
      various in vitro and in vivo systems is presented, and their advantages and
      disadvantages are discussed.

PMID- 20816707
TI  - Applying and comparing two chemometric methods in absorption spectral analysis of
      photopigments from Arctic microalgae.
AB  - Pigment absorption property of two arctic microalgae species (Skeletonema marinoi
      and Chlorella sp.) cultured at three temperatures (0, 4 and 8 degrees C) was
      analyzed. Carotenoids and chlorophyll (Chl) c were positive factors to the high
      cell activities and primary productivities of S. marinoi at 4 degrees C and 0
      degrees C, respectively; whereas Chl a had a positive effect on Chlorella sp. at
      all three temperatures, and carotenoids had a relatively high effect at 0 degrees
      C. The absorption locations of photopigments were analyzed in detail using both
      fourth derivative and Symlet-6 wavelet analysis. Both methods precisely detected
      pigments with a relative large content; the fourth derivative analysis
      specifically detected the existence of a Chl a peak at about 410 nm and showed
      better differentiation of diatoxanthin, whereas the wavelet analysis
      distinctively indicated the existence of chlorophyllide a, beta-carotene, and Chl
      c. The separation limit to pigment peaks of the fourth derivative spectra (4 nm)
      was 1 nm higher than that of the wavelet high-frequency spectra (3 nm). The
      wavelet high-frequency spectra were more stable in detecting pigment locations
      and were more effective in discriminating microalgae. Small algebraic difference
      of 10(-16) between the reconstructed absorption spectra obtained by the inverse
      wavelet transform and their corresponding original spectra also showed the
      validity of Symlet-6 wavelet in the detection of pigments. Another specific
      discovery of this research is the existence of a Chl a allomer in Chlorella sp.,
      which was detected by both methods.

PMID- 20816705
TI  - Cell metabolism: an essential link between cell growth and apoptosis.
AB  - Growth factor-stimulated or cancerous cells require sufficient nutrients to meet
      the metabolic demands of cell growth and division. If nutrients are insufficient,
      metabolic checkpoints are triggered that lead to cell cycle arrest and the
      activation of the intrinsic apoptotic cascade through a process dependent on the
      Bcl-2 family of proteins. Given the connections between metabolism and apoptosis,
      the notion of targeting metabolism to induce cell death in cancer cells has
      recently garnered much attention. However, the signaling pathways by which
      metabolic stresses induce apoptosis have not as of yet been fully elucidated.
      Thus, the best approach to this promising therapeutic avenue remains unclear.
      This review will discuss the intricate links between metabolism, growth, and
      intrinsic apoptosis and will consider ways in which manipulation of metabolism
      might be exploited to promote apoptotic cell death in cancer cells. This article
      is part of a Special Issue entitled Mitochondria: the deadly organelle.

PMID- 20816709
TI  - Effects of atropine and pralidoxime on neuronal actions of paraoxon in rat
      hippocampal slices.
AB  - The actions of paraoxon, an organophosphorus cholinesterase (ChE) inhibitor, on
      central synaptic transmission and somatic excitability, and the inhibitory
      effects of atropine, a non-selective muscarinic acetylcholine receptor (mAChR)
      antagonist, and pralidoxime (PAM), an oxime, on these actions were investigated.
      From rat hippocampal slices, CA1-population spikes (PSs) and CA1-field excitatory
      postsynaptic potentials (fEPSPs) at 0.1Hz were recorded using a multi-electrode
      array (MEA) system. Statistics were performed using ANOVA with Bonferroni/Dunn
      testing (n=6 in all data). Paraoxon (1MUM) depressed fEPSPs but did not
      significantly influence PSs. The fEPSP depression was inhibited by pre-,
      simultaneous and post-treatments with atropine (10MUM, p<0.01) and pre-treatment
      with PAM (10MUM, p<0.01). The insignificance of the paraoxon-induced PS change
      was not altered by pre-, simultaneous and post-treatments with atropine or by pre
      and post-treatments with PAM; however, PSs were significantly depressed by
      simultaneous treatment with paraoxon and PAM (p<0.01). Paraoxon-induced ChE
      inhibition depresses excitatory synaptic transmission and facilitates somatic
      excitability mediated by mAChRs, and the latter counteracts influence of the
      depressed synaptic transmission on somatic action potentials. Atropine and PAM
      prevent and depress the actions of paraoxon and are more effective with earlier
      treatment.

PMID- 20816708
TI  - Relationships between pre-stimulus gamma power and subsequent P300 and reaction
      time breakdown in schizophrenia.
AB  - INTRODUCTION: Little is known about the relationship between gamma-band
      oscillations prior to the arrival of a target stimulus and subsequent sensory
      processing and response execution. Although schizophrenia has been associated
      with abnormalities in gamma-band oscillations, P300, and reaction time (RT), few
      studies have examined the possible correspondence between these three
      neurobiological and behavioral markers in schizophrenia. To characterize the
      relationship between preparatory processes, information processing, and
      subsequent behavioral performance in schizophrenia, the present study
      investigated the relationships between pre-stimulus gamma-band power, RT and P300
      amplitude. METHODS: EEG and behavioral data were collected from 18 schizophrenia
      patients and 21 healthy controls during a conventional auditory oddball task.
      RESULTS: In controls, single-trial pre-stimulus gamma power was positively
      correlated with RT, and average P300 amplitude was positively correlated with
      average pre-stimulus gamma power. DISCUSSION: We interpret these findings as
      evidence that gamma power enhancement reflects a state of greater pre-stimulus
      preparation resulting in fuller evaluation of the target stimulus and therefore
      slower RT, as proposed by Jokeit and Makeig (1994). Consistent with previous
      research, schizophrenia patients exhibited RT slowing and P300 amplitude
      reductions relative to controls. Importantly, neither RT nor P300 amplitude was
      related to pre-stimulus gamma power in schizophrenia, suggesting a breakdown in
      the preparatory brain state critical for stimulus processing and later motor
      execution. The present findings underscore the behavioral significance of gamma
      band responses, and provide an additional link between gamma-band oscillations
      and information processing abnormalities in schizophrenia.

PMID- 20816710
TI  - In vitro anticancer activity of docetaxel-loaded micelles based on poly(ethylene
      oxide)-poly(epsilon-caprolactone) block copolymers: Do nanocarrier properties
      have a role?
AB  - In this paper we have investigated the behavior of core-shell poly(ethylene
      oxide)-poly(epsilon-caprolactone) (PEO-PCL) micelles derived from copolymers with
      linear triblock (TR) and 4-arm star-diblock (ST) architectures for the delivery
      of docetaxel (DTX). DTX was loaded inside micelles (DTX-TR(m) and DTX-ST(m)) with
      high efficiency and released slowly for more than two weeks. DTX-loaded micelles
      based on both copolymers had very similar properties in terms of mean size, zeta
      potential, loading ability and release rate in buffered saline. However, the
      stability of DTX-ST(m) was very poor in aqueous media with proteins resulting in
      a strong and progressive aggregation. We studied the effect of increasing
      concentrations of free DTX or DTX-loaded micelles on growth inhibition of human
      breast MCF-7 and MDA-MB468 and prostate PC3 and DU145 adenocarcinoma cell lines.
      DTX-loaded TR micelles induced cell growth inhibition similarly to free DTX
      whereas DTX-ST(m) showed lower cytotoxicity. On the other hand, by normalizing
      IC(50) values for the actual amount of DTX released from micelles in the medium,
      DTX-loaded ST micelles became more active than free DTX in all cell lines tested.
      Both free DTX and DTX-loaded TR micelles displayed a significantly lower
      cytotoxic activity in G(2)/M phase synchronized cells, whereas cytotoxicity of
      DTX-loaded ST micelles did not change. Cytotoxicity was related to micelle
      stability, uptake and release rate in cell culture media. Our results suggest
      that for a correct interpretation of cytotoxicity of nanocarriers, the evaluation
      of their behavior in biologically relevant conditions is of utmost importance to
      select proper systems for further in vivo testing.

PMID- 20816711
TI  - Nutrient content of products served by leading Australian fast food chains.
AB  - With more consumers purchasing meals outside the home, fast food products
      contribute substantially to daily energy intakes. Improving the nutrient
      composition of fast food would have significant health benefits. Nutrient content
      data for menu items provided by nine companies representing >90% of the fast food
      market in Australia were collected. Mean nutrient levels were compared between
      product categories and compared to currently accepted criteria for healthy foods.
      The majority of fast food products did not meet criteria for healthy options.
      Breakfast items had the highest mean sugar content (7.8 g/100 g) and saturated
      fat (5.5 g/100 g), and chicken items the highest total fat (13.2 g/100 g) and
      sodium (586 mg/100 g). There was marked variation in nutrient levels between
      similar products. There was a 10-fold variation in the total fat, saturated fat
      and sugar content of sandwiches, an 8-fold variation in saturated fat in burgers
      and >20-fold variation in the sugar and total fat content of salads. Differences
      were even greater per serve. The considerable variation in the nutrient content
      of comparable products suggests significant potential for reformulation. Even
      small improvements in composition could produce important health gains if
      implemented across all product categories by all companies in unison.

PMID- 20816712
TI  - Intrahippocampal Norleucine1-Angiotensin IV mitigates scopolamine-induced spatial
      working memory deficits.
AB  - Depletion of cholinergic neurons in the hippocampus has been implicated in memory
      impairment and Alzheimer's Disease (AD). The brain angiotensin AT4 receptor is co
      localized with cholinergic neurons, and the AT4 receptor has also been implicated
      in cognitive processing. The current investigation used the spatial win-shift
      version of the radial arm maze to determine the involvement of AT4 receptors in
      spatial working memory formation. We initially established that intrahippocampal
      scopolamine significantly impaired the spatial working memory performance of
      Sprague-Dawley rats in the radial arm maze. We also demonstrated that subsequent
      intrahippocampal infusions of Norleucine1-Angiotensin IV (Nle1-AngIV)
      significantly prevented the scopolamine-induced deficit. Consistent with
      previously published data on long-term spatial memory, our findings suggest that
      activation of AT4 receptors can compensate for impaired spatial working memory
      resulting from compromised muscarinic acetylcholine receptor function. We further
      demonstrate that the hippocampus is a site of action for Nle1-AngIV-mediated
      cognitive improvement.

PMID- 20816713
TI  - Angiotensin (1-7) reduces the cell volume of swollen cardiac cells and decreases
      the swelling-dependent chloride current. Implications for cardiac arrhythmias and
      myocardial ischemia.
AB  - The influence of angiotensin II and angiotensin (1-17) on cell volume and on the
      activation of ionic channels including the swelling-dependent chloride channel
      was reviewed. Particular emphasis was given to the influence of the balance
      between the ACE-angiotensin II and of the ACE2-angiotensin (1-7)-Mas receptor
      axis on heart cell volume regulation and on the swelling-dependent chloride
      current. The implications for myocardial ischemia and cardiac arrhythmias are
      discussed.

PMID- 20816714
TI  - Characterization of regulators of G-protein signaling RGS4 and RGS10 proteins in
      the postmortem human brain.
AB  - Regulator of G-protein signaling (RGS) proteins are a large family of proteins
      that accelerate GTPase rate of the Galpha subunits and therefore, negatively
      regulate G-protein signaling. Expression of RGS4 and RGS10 proteins was
      characterized in human prefrontal cortex attending to methodological (subcellular
      localization, antibody specificity and sensitivity, postmortem delay (PMD) and
      storage conditions of the samples) and demographic issues (age and gender of the
      subjects). Anti-RGS4 (N-16) antibody revealed a unique and specific band of 38
      kDa that was highly enriched in the plasma membrane. Anti-RGS10 (C-20) antibody
      revealed two specific bands of 24 and 27kDa, corresponding to two possible
      isoforms of this protein, which were predominantly localized in the cytosol.
      Antibody dilution and protein linearity studies confirmed the sensitivity of the
      signal. A large number of samples from 58 individuals presenting well spread PMD,
      storage time, age of the subjects at the time of death, and male and female
      distribution were studied. A positive linear relationship between the age and
      RGS4 immunoreactivity was observed. There was a negative influence of PMD on the
      RGS10 27 kDa band immunoreactivity but a positive relationship emerged between
      the PMD and RGS4 immunoreactivity. Storage time of the samples did not have any
      influence on RGS4 nor on RGS10 immunoreactivity, showing their stability at -70
      degrees C. When studying the RGS4 and RGS10 protein expression density in males
      and females, no significant difference was found between groups. This study
      demonstrates that RGS4 and RGS10 proteins can be detected by immunoreactive
      techniques in postmortem human brain cortex. The study provides important
      matching conditions that should be taken into account in postmortem brain studies
      of neuropsychiatric diseases.

PMID- 20816715
TI  - Obsessive compulsive disorder and symptoms may have different effects on
      schizophrenia.
AB  - The aim of this study is to investigate the possible different effects of
      obsessive compulsive disorder (OCD) and obsessive compulsive symptoms (OCS) on
      schizophrenia illness in regard to clinical characteristics such as severity of
      symptomatology. We included 184 patients with schizophrenia on monotherapy with a
      stable dose of antipsychotics for at least three months. Severity of clinical
      symptoms was evaluated by Positive and Negative Syndrome Scale. OCS was examined
      by Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Checklist. We also assessed OCD
      by using Y-BOCS. Seventeen percent of the patients were diagnosed with current
      OCD, while 17.4% of the patients were found to have OCS without OCD. Age of onset
      for OCD group was earlier than non-OCS group (p=0.007). The rate of occupation
      was higher (p=0.001), prevalence of other comorbid psychiatric disorders was
      lower (p=0.05), number of hospitalization was lower (p=0.03), GAF score was
      higher (p=0.03) and duration of education was longer (p=0.02) in the OCS group
      than in the non-OCS group. The rate of occupation was higher (p=0.04) and that
      rate of comorbid psychiatric disorders was lower (p=0.01) in the OCS group than
      in the OCD group. We found more OCS in patients using atypical antipsychotics
      (p=0.03). Our findings suggest that OCD and OCS might have different effects on
      schizophrenia.

PMID- 20816716
TI  - The folic acid combined with 17-beta estradiol produces antidepressant-like
      actions in ovariectomized rats forced to swim.
AB  - Folic acid or 17-beta estradiol produces antidepressant effects, either alone or
      combined with several antidepressants. However, the antidepressant-like actions
      of folic acid combined with 17-beta estradiol in the forced swimming test (FST)
      have not been tested before. Thus, in the present study, ovariectomized female
      rats received folic acid (5.0 nmol/i.c.v., P<0.05; 10.0 nmol/ i.c.v., P<0.05; or
      50mg/kg, P<0.05, p.o.; 75.0; mg/kg, P<0.05, p.o.), or fluoxetine (20.0mg/kg,
      P<0.05; 25.0mg/kg, P<0.05) or 17-beta estradiol (10.0 MUg/rat, P<0.05; 20.0
      MUg/rat, P<0.05) and they displayed reduced immobility by increasing swimming
      behavior when they were tested in the FST. Combination of subthreshold doses of
      folic acid (2.5 nmol/i.c.v.; or 25.0mg/kg, p.o.) with subthreshold doses of 17
      beta estradiol (5.0 MUg/rat, P<0.05) or with subthreshold doses of fluoxetine
      (15.0mg/kg, P<0.05) produced antidepressant-like actions. Ketanserin was used to
      evaluate the participation of the drugs used in the serotonergic pathway;
      ketanserin cancelled the antidepressant-like actions of the several combinations
      used. In conclusion, folic acid alone or combined with estradiol or fluoxetine in
      the FST reduced immobility in the FST. These antidepressant-like actions probably
      were due to modifications of the serotonergic system since swimming behavior was
      increased and these effects were cancelled by ketanserin.

PMID- 20816717
TI  - Determination of volatile nitrosamines in various meat products using
      comprehensive gas chromatography-nitrogen chemiluminescence detection.
AB  - An optimized method was developed for the extraction, pre-concentration and
      analysis of nitrosamines (NAs) in various meat products. Values of
      reproducibility, linearity, limit of detection (LOD) and limit of quantitation
      (LOQ) for six NA standards (N-nitrosodimethylamine, N-nitrosodiethylamine, N
      nitrosodi-n-propylamine, N-nitrosopyrrolidine, N-nitrosopiperidine, N-nitrosodi-n
      butylamine) were determined. The LODs using this method were between 1.66-3.86
      and LOQs between 6.96-16.71 MUg L(-1). The screening of four different types of
      meat samples (sausage, salami, sucuk and doner kebab) showed that all samples
      contained levels of various NAs, identified with high confidence using
      comprehensive gas chromatography (GCxGC) and a fast responding element specific
      nitrogen chemiluminescence detector (NCD). The sum of the six NAs were highest in
      the doner kebab samples, being between 0.51-16.63 MUg kg(-1) and were lowest in
      the sausage samples at 0.45-2.93 MUg kg(-1). The described method is simple,
      rapid, selective and sensitive.

PMID- 20816718
TI  - Brain glutathione as a target for aetiological factors in neurolathyrism and
      konzo.
AB  - Both neurolathyrism and konzo are associated with the nutritional dependence of
      human populations on a single plant food. These diseases express themselves as
      chronic disorders of upper motor neurones, leading to signs and symptoms that
      characterise amyotrophic lateral sclerosis (motor neurone disease). The plant
      food associated with neurolathyrism is grass pea, which contains the neurotoxic
      beta-N-oxalyl-alpha,beta-diaminopropionic acid (beta-ODAP). The plant food
      associated with konzo is cassava, which may contain significant concentrations of
      cyanogenic glycosides and their degradation products. A monotonous diet of grass
      pea is likely to generate nutritional deficiencies; it is proposed that one of
      these, plasma methionine deficiency, may predispose neurones to the neurotoxic
      effects of beta-ODAP. Subjects suffering from konzo also have low concentrations
      of plasma methionine as a result of a dietary deficiency of this amino acid.
      However, the plasma cystine concentration is also compromised because cyanide
      released from cyanogenic glycosides in cassava probably reacts with plasma
      cystine non-enzymatically. The product of this reaction is 2-imino-4-thiazolidine
      carboxylic acid. Since both plasma methionine and cystine are used for
      glutathione synthesis it seems likely that one common feature that leads to motor
      neurone death in neurolathyrism and konzo is the depletion of glutathione in the
      central nervous system.

PMID- 20816719
TI  - Evaluation of a urinary kidney biomarker panel in rat models of acute and
      subchronic nephrotoxicity.
AB  - Several novel urinary kidney biomarkers were recently approved by the US-FDA and
      EMA for improved detection of nephrotoxicity, but few data regarding their
      performance are publicly available so far. In this study, we investigated the
      potential of some of the newly accepted makers (Kim-1, beta-2-microglobulin,
      cystatin C, clusterin) along with six additional urinary key proteins of kidney
      injury (GST-alpha, Timp-1, VEGF, calbindin, NGAL/lipocalin-2, osteopontin) to
      detect proximal tubule damage in the rat model studying either acute drug-induced
      kidney injury or subchronic nephrotoxicity. Candidate proteins were measured in
      urine samples obtained from rats treated with gentamicin (0, 60 and 120 mg/kg bw
      for 7 days), BI-3 [3-pyrrolidineacetic acid, 5-[[[4'-[imino[(methoxycarbonyl)
      amino]methyl] [1,1'-biphenyl]-4-yl]oxy]methyl]-2-oxo-, methyl ester,(3S-trans)]
      (0, 100, and 1000 mg/kg bw for up to 14 days) or with the mycotoxin ochratoxin A
      (OTA) (0, 21, 70 and 210 MUg/kg bw for up to 90 days) using a Luminex((r))
      xMAP((r)) platform. Cystatin C and NGAL appeared to be the most sensitive
      indicators of gentamicin nephrotoxicity, with significant changes occurring as
      early as day 1, and importantly before alterations in serum creatinine or blood
      urea nitrogen (BUN). Altered urinary excretion of KIM-1, clusterin, calbindin and
      Timp-1 accompanied by a rise in BUN was observed in rats with BI-3 at 1000 mg/kg
      bw for 14 days. In contrast, histopathological alterations induced by OTA, which
      preceded effects on traditional clinical parameters, were best reflected by
      changes in urinary Kim-1. Overall, our data confirm increased sensitivity of new
      markers as compared to traditional clinical chemistry parameters.

PMID- 20816720
TI  - Prediction of soman-induced cerebral damage by distortion product otoacoustic
      emissions.
AB  - The organophosphorus nerve agent soman is an irreversible cholinesterase (ChE)
      inhibitor that can produce long-lasting seizures and seizure-related brain damage
      (SRBD) in which acetylcholine and glutamate are involved. Since these
      neurotransmitters play a key-role in the auditory function, it was hypothesized
      that a hearing test may be an efficient way for detecting the central effects of
      soman intoxication. In the present study, distortion product otoacoustic
      emissions (DPOAEs), a non-invasive audiometric method, were used in rats
      administered with soman (70 MUg/kg). Four hours post-soman, DPOAE intensities
      were significantly decreased. They returned to baseline one day later. The
      amplitude of the temporary drop of the DPOAEs was well related to the severity of
      the intoxication. The greatest change was recorded in the rats that survived long
      lasting convulsions, i.e. those that showed the highest ChE inhibition in brain
      and severe encephalopathy. Furthermore, the administration, immediately after
      soman, of a three-drug therapy composed of atropine sulfate, HI-6 and avizafone
      abolished the convulsions, the transient drop of DPOAEs at 4h and the occurrence
      of SRBD at 28 h without modifying brain ChE inhibition. This showed that DPOAE
      change was not directly related to soman-induced inhibition of cerebral ChE but
      rather to its neuropathological consequences. The present findings strongly
      suggest that DPOAEs represent a promising non-invasive tool to predict SRBD
      occurrence in nerve agent poisoning and to control the efficacy of a
      neuroprotective treatment.

PMID- 20816721
TI  - Estrogens repress PGC1-alpha expression in the uterus.
AB  - PGC-1alpha is a transcriptional coactivator that is highly involved in several
      aspects of regulation of metabolism, including mitochondrial biogenesis and
      activity. Using several in vivo models, we here report that the expression of PGC
      1alpha is repressed by estrogens in the mouse specifically in the uterus. In the
      absence of estrogens, expression of PGC-1alpha target genes involved in
      mitochondrial activity is activated, but not mitochondrial biogenesis. Regulation
      of PGC-1alpha expression by estrogens also occurs in Ishikawa human uterine cells
      at the promoter level and involve modulation of c-jun expression.

PMID- 20816722
TI  - Parametric analysis of thermal preference following sleep deprivation in the rat.
AB  - A thermal preference task was used to assess the effects of sleep deprivation on
      nociceptive behavior using hot and cool stimuli. The thermal preference apparatus
      allowed male rats to move freely from a hot thermal plate (44.7 degrees C) to an
      adjacent plate at neutral (33.5 degrees C) or cold temperatures (1.3-11 degrees
      C). Investigators recorded occupancy on the colder side, frequency of movements
      between the 2 compartments, and first escape latency from the cold side.
      Parametric analysis of thermal preference indicated that behavioral allocation
      was related to temperature ranges previously associated with activation of
      thermal nociceptors. A 50% occupancy rate was determined from a stimulus-response
      function identifying 1.3 degrees C vs. 44.7 degrees C as optimal temperatures.
      This temperature combination was then used to test the effects of sleep
      deprivation for 48h using the pedestal-over-water method on response allocation
      to the 2 temperature zones. Sleep deprivation decreased time spent on the cooled
      plate. Cumulative occupancy indicated differential effects for sleep deprivation
      with the rats preferring to remain on the hot side vs. the cold side, suggesting
      that sleep deprivation increased the nociceptive properties of the cold stimulus.

PMID- 20816724
TI  - Interferon-beta treatment normalises the inhibitory effect of serum from multiple
      sclerosis patients on oligodendrocyte progenitor proliferation.
AB  - Interferon-beta (IFN-beta) is an established therapy for relapsing-remitting
      multiple sclerosis (MS). However, the mode of action and the effect on
      oligodendrocytes are not yet clear. In this study, we examined the influence of
      an IFN-beta therapy on the proliferation and differentiation of primary
      oligodendrocyte precursor cells (OPC) in mixed glial cultures. Mixed glial
      cultures were incubated for 5 days in medium supplemented with 10% of sera from
      healthy controls, untreated MS patients and IFN-beta treated MS patients.
      Proliferation and differentiation of OPC were determined by immunocytochemistry.
      Proliferation of OPC was significantly inhibited by sera from untreated MS
      patients compared to healthy controls, while this effect was almost completely
      reversed by serum from IFN-beta treated MS patients. No effect on OPC
      differentiation was observed. A prospective and longitudinal analysis of a second
      cohort of MS patients treated with IFN-beta showed that the reversal of
      inhibition of OPC proliferation was evident after 12 months of treatment but not
      during the first 6 months. Thus, our results suggest that IFN-beta treatment has
      the capacity to revert the inhibitory effect of serum from MS patients on OPC
      proliferation. It is currently not clear what this means for regenerative
      processes.

PMID- 20816723
TI  - The trafficking of Na(V)1.8.
AB  - The alpha-subunit of tetrodotoxin-resistant voltage-gated sodium channel Na(V)1.8
      is selectively expressed in sensory neurons. It has been reported that Na(V)1.8
      is involved in the transmission of nociceptive information from sensory neurons
      to the central nervous system in nociceptive [1] and neuropathic [24] pain
      conditions. Thus Na(V)1.8 has been a promising target to treat chronic pain. Here
      we discuss the recent advances in the study of trafficking mechanism of Na(V)1.8.
      These pieces of information are particularly important as such trafficking
      machinery could be new targets for painkillers.

PMID- 20816725
TI  - Isolectin B4binding in populations of rat trigeminal ganglion cells.
AB  - We have recently classified dissociated trigeminal ganglion cells into nine types
      using electrophysiological current signatures. In the present study, we
      investigated the relationship between isolectin B(4) (IB(4)) binding and the cell
      types in rat trigeminal ganglion cells. We found that IB(4) was bound to all type
      2 cells and more than 70% of cell types 1 and 13; however, it was bound to less
      than 20% of cell types 7 and 8 and did not bind at all to cell types 3-5 and 9.
      Thus, each trigeminal ganglion cell type showed high homogeneity in IB(4)
      binding. These results correspond to reported IB(4) binding profiles in the
      matched dorsal root ganglion cell types, except for types 5 and 7.

PMID- 20816726
TI  - Isolation and structural characterization of glycosides from an anti-angiogenic
      extract of Monnina obtusifolia H.B.K.
AB  - Angiogenesis, the growth of new blood vessels from the pre-existing vasculature
      is of physiological and pathological importance. Substantial data over the last
      decade has implicated uncontrolled angiogenesis with various pathological states.
      Vascular endothelial growth factors (VEGFs) play a critical role in its
      regulation, and have become one of the most interesting anti-angiogenesis
      targets. We have investigated the anti-angiogenic potential of plant extracts in
      a preliminary ELISA screening. The n-BuOH extract obtained from the leaves of
      Monnina obtusifolia (Polygalaceae) demonstrated an inhibition of VEGF-A or
      Placental Growth Factor interaction with Flt-1 (VEGF receptor 1), with an
      inhibition over 50% in particular for VEGF-A/Flt-1 interaction at a concentration
      of 500 MUg/mL. Successively fractionation of the bioactive n-BuOH extracts of M.
      obtusifolia aerial parts led to the isolation of six new compounds, 1-O-(4
      hydroxy-2-methylene-butanoic acid)-6-O-beta-D-(4-hydroxy-2-methylene-butanoyl)
      glucopyranose (1), 1-O-(isopentenyl)-6-O-beta-D-(4-hydroxy-2-methylene-butanoyl)
      glucopyranose (2), 1-O-(4-hydroxy-2-methylene-butanoic acid)-6-O-beta-D
      (isovaleroyl)-glucopyranose (3), 1-O-(3-methylbut-3enyl)-6-O-beta-D-(isovaleroyl)
      glucopyranose (4), two new sucrose esters, 3,4-O-beta-D-di-feruloyl
      fructofuranosyl-6-O-alpha-D-(p-coumaroyl)-glucopyranoside (5), and 3,4-O-beta-D
      di-feruloyl-fructofuranosyl-6-O-alpha-D-(caffeoyl)-glucopyranoside (6), together
      with known flavonoids. Their structures were established on the basis of detailed
      spectral analysis. Since none of the isolated compounds showed a relevant
      inhibition of VEGFs, the biological activity observed for the butanolic extract
      might be due to the presence of a combination of compounds acting
      synergistically.

PMID- 20816727
TI  - The full-length isoform of the mouse pleckstrin homology domain-interacting
      protein (PHIP) is required for postnatal growth.
AB  - PHIP was isolated as an insulin receptor substrate 1 (IRS-1) interacting protein.
      To date, the physiological roles of PHIP remain unknown. Here we show that mice
      lacking PHIP1, the full-length isoform of PHIP, are born at normal size but
      suffer a 40% growth deficit by weaning. PHIP1 mutant mice develop hypoglycemia
      and have an average lifespan of 4-5 weeks. PHIP1-deficient mouse embryonic
      fibroblasts (MEFs) grow markedly slower than wild-type MEFs, but exhibit normal
      AKT phosphorylation and an increased cell proliferation in response to IGF-1
      treatment. Together these results suggest that PHIP1 regulates postnatal growth
      in an IGF-1/AKT pathway-independent manner.

PMID- 20816728
TI  - Arsenite exposure in human lymphoblastoid cell lines induces autophagy and
      coordinated induction of lysosomal genes.
AB  - Chronic exposure to inorganic arsenic is associated with diverse, complex
      diseases, making the identification of the mechanism underlying arsenic-induced
      toxicity a challenge. An increasing body of literature from epidemiological and
      in vitro studies has demonstrated that arsenic is an immunotoxicant, but the
      mechanism driving arsenic-induced immunotoxicity is not well established. We have
      previously demonstrated that in human lymphoblastoid cell lines (LCLs), arsenic
      induced cell death is strongly associated with the induction of autophagy. In
      this study we utilized genome-wide gene expression analysis and functional assays
      to characterize arsenic-induced effects in seven LCLs that were exposed to an
      environmentally relevant, minimally cytotoxic, concentration of arsenite (0.75
      MUM) over an eight-day time course. Arsenic exposure resulted in inhibition of
      cellular growth and induction of autophagy (measured by expansion of acidic
      vesicles) over the eight-day exposure duration. Gene expression analysis revealed
      that arsenic exposure increased global lysosomal gene expression, which was
      associated with increased functional activity of the lysosome protease, cathepsin
      D. The arsenic-induced expansion of the lysosomal compartment in LCL represents a
      novel target that may offer insight into the immunotoxic effects of arsenic.

PMID- 20816729
TI  - Chitosan nanoparticles show rapid extrapulmonary tissue distribution and
      excretion with mild pulmonary inflammation to mice.
AB  - Pulmonary delivery of nanoparticles (NP) conjugated with therapeutic agents has
      been considered recently for both lung disorders and systemic circulation.
      Hydrophobically modified glycol chitosan (HGC) NP have previously shown excellent
      deposition to the tumor site and non-destructive intracellular release. Here, we
      evaluated the kinetics and toxicity of HGC NP by intratracheal instillation to
      mice. HGC NP showed a positive charge and average hydrodynamic size was around
      350 nm. The half-life of NP in the lung was determined as 131.97+/-50.51 h. NP
      showed rapid uptake into systemic circulation and excretion via urine which was
      peaked at 6h after instillation. Although HGC NP were distributed to several
      extrapulmonary organs, the levels were extremely low and transient. HGC NP
      induced transient neutrophilic pulmonary inflammation from 6h to day 3 after
      instillation. Expression of pro-inflammatory cytokines (IL-1beta, IL-6, and TNF
      alpha) and chemokine (MIP-1alpha) in lung showed an increase from 1h to 24h after
      instillation and recovered thereafter. Our findings suggest that HGC NP can be
      successful candidates for use as pulmonary delivery vehicles, owing to their
      excellent biocompatibility, transiency, and low pulmonary toxicity, and property
      of rapid elimination without accumulation.

PMID- 20816731
TI  - Absorption and safety of alendronate, a nitrogen-containing bisphosphonate, after
      intrapulmonary administration in rats.
AB  - Alendronate, a nitrogen-containing bisphosphonate, has been used as a first
      choice drug for the treatment of hypercalcemia and osteoporosis. In the present
      study, we examined the absorption and safety of alendronate after intrapulmonary
      administration in rats. The bioavailability (BA) of alendronate after
      intrapulmonary administration was 47% at a dose of 5 mg/kg, while the BA after
      oral administration was only 2.9% at a dose of 50 mg/kg in rats. Plasma calcium
      level, an index of the pharmacological effect of alendronate, was effectively
      reduced after intrapulmonary administration of alendronate. Furthermore,
      alendronate continuously reduced the increase in plasma calcium levels for 9 days
      after a single intrapulmonary administration in rats with 1alpha-hydroxyvitamin
      D(3)-induced hypercalcemia. Intrapulmonary administration of alendronate also
      effectively suppressed the decrease in bone mass in a rat model of osteoporosis.
      Alendronate significantly increased the activity of lactate dehydrogenase (LDH)
      in bronchoalveolar lavage fluid (BALF), indicating that pulmonary mucosal damage
      was induced by intrapulmonary administration of alendronate. However, co
      administration of superoxide dismutase (SOD) with alendronate completely
      suppressed the alendronate-induced increase in LDH activity in BALF, while
      maintaining sufficient pulmonary absorption and therapeutic effects of
      alendronate in rats with 1alpha-hydroxyvitamin-D(3)-induced hypercalcemia. These
      findings indicated that the lung is a promising, noninvasive alternative route
      for the delivery of alendronate in the treatment of bone diseases.

PMID- 20816732
TI  - Rational development of taste masked oral liquids guided by an electronic tongue.
AB  - Human taste testing is often associated with ethical concerns, organizational and
      validation issues. Electrochemical sensor array systems, so called electronic
      tongues, offer an alternative to assess the taste of multi-component liquid
      formulations. Therefore, it should be investigated how an electronic tongue can
      be implemented in the rational development of taste masked formulations. Taste
      masking of bitter tasting quinine hydrochloride (QH) in a liquid formulation was
      carried out by screening sweetening agents (sucrose, glucose, fructose, mannitol,
      sucralose, sodium saccharin, acesulfame potassium, and monoammonium
      glycyrrhizinate), strong and weak cation ion exchange (IE) resins (AmberliteTM
      IRP69, AmberliteTM IRP88, and Indion 234), and soluble complexing agents (alpha-,
      beta-, hydroxypropyl-beta-, sulfobutyl ether-beta- and gamma-cyclodextrin and
      maltodextrin). AmberliteTM IRP88 showed the best binding capacity for quinine
      (1.9 g quinine/1 g IE). The addition of sulfobutyl ether-beta-cyclodextrin (SBE
      beta-CD) could significantly reduce the bitter taste of QH (79% reduction of free
      QH). The SBE-beta-CD formulation was further improved by adding sodium saccharin
      as secondary taste masking agent. It could also be shown that presence of
      strawberry flavor and the preservative domiphen bromide does not affect
      evaluation of taste masking efficiency. The introduced stepwise approach was
      shown to be applicable to rationally develop novel taste masked formulations.

PMID- 20816730
TI  - Biological activity of heterologous murine interleukin-10 and preliminary studies
      on the use of a dextrin nanogel as a delivery system.
AB  - Interleukin-10 (IL-10) is an anti-inflammatory cytokine, which active form is a
      non-covalent homodimer with two intramolecular disulphide bonds essential for its
      biological activity. A mutated form of murine IL-10 was successfully expressed in
      E. coli, recovered and purified from inclusion bodies. Its ability to reduce
      tumor necrosis factor alpha synthesis and down-regulate class II major
      histocompatibility complex molecules expression on endotoxin-stimulated bone
      marrow-derived macrophages was confirmed, and shown to be similar to that of a
      commercially available IL-10. Given the potential of IL-10 for application in
      various medical conditions, it is essential to develop systems that can
      effectively deliver the protein. In this work it is shown that a dextrin nanogel
      effectively incorporate IL-10, stabilize, and enable the slow release of
      biologically active IL-10 over time. Altogether, these results demonstrate the
      suitability of dextrin nanogel to be used as a system for the controlled release
      of IL-10.

PMID- 20816733
TI  - Effect of force feeder on tablet strength during compression.
AB  - Mechanical strength of tablets is an important quality attribute, which depends
      on both formulation and process. In this study, the effect of process variables
      during compression on tablet tensile strength and tabletability (the ratio of
      tensile strength to compression pressure) was investigated using a model
      formulation. Increase in turret and force feeder speeds reduced tablet tensile
      strength and tabletability. Turret speed affected tabletability through changes
      in dwell time under the compression cam and the kinetics of consolidation of
      granules in the die cavity. The effect of force feeder was attributed to the
      shearing of the granulation, leading to its over-lubrication. A dimensionless
      equation was derived to estimate total shear imparted by the force feeder on the
      granulation in terms of a shear number. Scale-independence of the relationship of
      tabletability with the shear number was explored on a 6-station Korsch press, a
      16-station Betapress, and a 35-station Korsch XL-400 press. The use of this
      relationship, the exact nature of which may be formulation dependent, during
      tablet development is expected to provide guidance to the scale-up and
      interchangeability of tablet presses.

PMID- 20816734
TI  - Bone implants modified with cyclodextrin: study of drug release in bulk fluid and
      into agarose gel.
AB  - The aim of this work was to better understand the importance of the type of
      experimental setup used to monitor antibiotic release from functionalized
      hydroxyapatite implants. Microporous hydroxyapatite discs were prepared by
      sintering and subsequently functionalized with hydroxypropyl-beta-cyclodextrin
      (HPbetaCD) polymer crosslinked with butanetetracarboxylic acid. On one hand,
      polymerization was performed within the implant after its impregnation with the
      monomers (CD-HA-M implant). On the other hand, a pre-synthesized HPbetaCD polymer
      was loaded and fixed onto the HA discs (CD-HA-P implant). Both types of implants
      were soaked with ciprofloxacin hydrochloride or vancomycin hydrochloride solution
      and dried at 37 degrees C. The DSC study highlighted that the cyclodextrin
      polymer could interfere with both drugs, due to the carboxylic groups carried by
      the crosslinks. Drug release was measured into phosphate buffered saline pH 7.4
      in agitated vials, or into agarose gels to more realistically mimic in vivo
      conditions. Importantly, in all cases, drug release into agarose gels was much
      slower than into well-agitated phosphate buffer. Non-functionalized discs
      displayed faster drug release because no complex could be formed and/or due to
      the absence of the HPbetaCD polymer network hindering drug diffusion within the
      implant pores. In the case of ciprofloxacin hydrochloride, drug release from the
      CD-HA-M implants was faster than drug release from the CD-HA-P implants due to
      the different polymer structures resulting in different complexation strengths,
      whereas in the case of vancomycin hydrochloride the release patterns were similar
      because vancomycin hydrochloride was not included into the cyclodextrin. The
      agarose gel method seems more biorelevant and discriminatory than the vial method
      for drug release measurements from bone implants.

PMID- 20816735
TI  - In-line ultrasound measurement system for detecting tablet integrity.
AB  - An ultrasound measurement system for tablet defect detection is introduced. The
      measurement system was implemented in an eccentric single station tabletting
      apparatus, where ultrasound transducers were placed inside the upper and lower
      punches. These instrumented punches were then used to measure the speed of sound
      and ultrasound attenuation values in both intact and defective tablets made from
      dibasic calcium phosphate, microcrystalline cellulose and lactose monohydrate.
      Ultrasound attenuation was found to be a very sensitive method to discriminate
      defective tablets from intact ones. In addition, it was found that the determined
      ultrasound attenuation was different between all three materials used in this
      study, which indicates that different materials could be distinguished from one
      another by this detection method.

PMID- 20816736
TI  - In vitro degradation behavior of poly(lactide)-poly(ethylene glycol) block
      copolymer micelles in aqueous solution.
AB  - Self-assembling micelles were prepared from polylactide-poly(ethylene glycol)
      (PLA-PEG) block copolymer by using two different methods: direct dissolution and
      dialysis. The in vitro degradation properties of the micelles were investigated
      at 37 degrees C and monitored by using various techniques. During the
      investigated degradation time, the size of micelles by dialysis remains stable,
      while that of micelles by direct dissolution first increases, followed by a
      collapse of micellar structure. The composition of PLA-PEG copolymers greatly
      affects the degradation of micelles. Micelles with longer hydrophobic PLA blocks
      exhibit less size changes due to more compact structure. On the other hand, the
      structural integrity of L/D mixed micelles is preserved for longer time than that
      of single micelles, in agreement with the stereocomplexation effect between L-PLA
      and D-PLA blocks. As degradation proceeds, the average molar mass of copolymer
      decreases and the distribution becomes wider, especially for micelles by dialysis
      and L/D mixed micelles with a more compact structure. Additionally, the PEG
      content in the copolymer chains increases during degradation, leading to a
      decrease of glass transition and crystallization temperature of the copolymers.
      However, the residual LA fragments produced by degradation disfavors the
      crystallization of PEG blocks, thus resulting in the decrease of melting
      temperature and melting enthalpy.

PMID- 20816737
TI  - Antitumor activity of quaternized chitosan-based electrospun implants against
      Graffi myeloid tumor.
AB  - Nanofibrous implants containing quaternized chitosan (QCh), poly(L-lactide-co-D,L
      lactide) (coPLA), and the antitumor drug doxorubicin (DOX) were fabricated by
      electrospinning. The surface chemical composition and the morphology of the
      implants were characterized by XPS and SEM. In vitro cell viability studies
      demonstrated that QCh- and DOX-based implants exhibited high cytotoxicity against
      Graffi tumor cells. The implants efficiently inhibited the growth of Graffi tumor
      in hamsters with minimum weight loss. Insertion of QCh/coPLA/DOX implants in the
      place of removed tumor led to an increase in the animal survival rate and to a
      decrease in the percentage of recurrences.

PMID- 20816738
TI  - Synergistic effects between natural histone mixtures and polyethylenimine in non
      viral gene delivery in vitro.
AB  - Nanoparticles made of plasmid DNA (pDNA) and cationic polymers are promising
      strategies for non-viral gene delivery. However, many cationic polymers are toxic
      to cells when used in higher concentrations. Positively charged proteins, such as
      histones, are biodegradable and a good alternative, especially for potential in
      vivo applications. It has previously been shown that histones are able to complex
      DNA and mediate transfection of cells. To investigate possible synergistic
      effects between the different histone types and to avoid the use of recombinant
      proteins, we analysed whether natural histone mixtures would be functional as
      gene carriers. Core and linker histones from calf thymus and from chicken
      erythrocytes were used to transfect different cell lines. The protein mixtures
      efficiently complexed the pDNA, and the resulting particles entered the cells.
      However, only marginal expression of the gene encoded by the pDNA was observed.
      Transfection rates increased drastically when minimal amounts of the basic
      polymer polyethylenimine (PEI) were added to the particles. Neither PEI nor
      histones alone mediated any transfection under the conditions where a combination
      of both worked efficiently, and the combined particles were well tolerated by the
      cells. These results demonstrate that histone mixtures from natural sources in
      combination with minimal amounts of PEI can be used as gene carriers. This might
      have consequences for the development of novel gene delivery strategies, such as
      DNA vaccines, with minimal side-effects.

PMID- 20816739
TI  - Dynamic modulation of short-term synaptic plasticity in the auditory cortex: the
      role of norepinephrine.
AB  - Norepinephrine (NE) is an important modulator of neuronal activity in the
      auditory cortex. Using patch-clamp recording and a pair pulse protocol on an
      auditory cortex slice preparation we recently demonstrated that NE affects
      cortical inhibition in a layer-specific manner, by decreasing apical but
      increasing basal inhibition onto layer II/III pyramidal cell dendrites. In the
      present study we used a similar protocol to investigate the dependence of
      noradrenergic modulation of inhibition on stimulus frequency, using 1s-long train
      pulses at 5, 10, and 20 Hz. The study was conducted using pharmacologically
      isolated inhibitory postsynaptic currents (IPSCs) evoked by electrical
      stimulation of axons either in layer I (LI-eIPSCs) or in layer II/III (LII/III
      eIPSCs). We found that: 1) LI-eIPSC display less synaptic depression than LII/III
      eIPSCs at all the frequencies tested, 2) in both type of synapses depression had
      a presynaptic component which could be altered manipulating [Ca2+]0, 3) NE
      modestly altered short-term synaptic plasticity at low or intermediate (5-10 Hz)
      frequencies, but selectively enhanced synaptic facilitation in LI-eIPSCs while
      increasing synaptic depression of LII/III-eIPSCs in the latest (>250 ms) part of
      the response, at high stimulation frequency (20 Hz). We speculate that these
      mechanisms may limit the temporal window for top-down synaptic integration as
      well as the duration and intensity of stimulus-evoked gamma-oscillations
      triggered by complex auditory stimuli during alertness.

PMID- 20816740
TI  - Reference gene selection for quantitative real-time polymerase chain reaction in
      Populus.
AB  - Accurate quantification of gene expression with quantitative real-time polymerase
      chain reaction (qRT-PCR) relies on the choice of an appropriate reference gene.
      In this study, nine candidate reference genes were selected to study the
      expression stability for qRT-PCR normalization in adventitious rooting of Populus
      hardwood cuttings. geNorm, NormFinder, and BestKeeper analysis revealed that
      actin isoform B (ACT) was the most unstable gene across developmental stages,
      whereas elongation factor 1 alpha (EF1a) and 18S recombinant RNA (18S) emerged as
      the most appropriate reference genes for qRT-PCR analysis in this complex
      developmental process.

PMID- 20816741
TI  - Electrophoretic analysis of PEGylated hemoglobin-based blood substitutes.
AB  - Polyethylene glycol (PEG)-conjugated hemoglobins, a novel class of blood
      substitutes, were investigated by a combination of native and denaturing one- and
      two-dimensional polyacrylamide gel electrophoresis (PAGE) coupled with the
      microspectrophotometric characterization of single bands and the functional
      analysis of electrophoretically separated fractions. For these intrinsically
      heterogeneous products, the molecular mass, the size distribution, and the degree
      of PEGylation are strictly correlated to their side effects and, therefore, are
      crucial pieces of information to evaluate their safety and efficacy. The
      PEGylation pattern was shown to strongly depend on the quaternary conformation of
      hemoglobin during the reaction, and the degree of conjugation was shown to
      correlate with the oxygen binding properties of the individual
      electrophoretically separated fractions. Moreover, small but not negligible
      fractions of underivatized tetramers, known to be responsible for serious side
      effects, were detected even in preparations with a high average degree of
      PEGylation. Overall, this approach might be exploited to characterize other
      products of protein PEGylation, an increasingly relevant technology for the
      optimization of the pharmacokinetic properties of protein-based drugs.

PMID- 20816743
TI  - A modified plasmid vector pCMV-3Tag-LIC for rapid, reliable, ligation-independent
      cloning of polymerase chain reaction products.
AB  - Here we present a modified vector pCMV-3Taq-LIC for a rapid, simple, and
      relatively cheap method to build expression constructs. After being digested by
      Nt.BspQI and EcoRV, a lineal vector with specific 11-base single overhangs is
      obtained. Polymerase chain reaction (PCR) products with complementary overhangs
      are created by building appropriate extensions into the primers and treating them
      with T4 DNA polymerase. The annealing of the insert and the vector is performed
      in the absence of ligase by simple mixing of the DNA fragments. This process is
      very specific because only the desired products can form. Using this vector, we
      successfully constructed hnRNP K full-length complementary DNA (cDNA) expression
      plasmid.

PMID- 20816742
TI  - Coumarin-suberoylanilide hydroxamic acid as a fluorescent probe for determining
      binding affinities and off-rates of histone deacetylase inhibitors.
AB  - Histone deacetylases (HDACs) are intimately involved in epigenetic regulation
      and, thus, are one of the key therapeutic targets for cancer, and two HDAC
      inhibitors, namely suberoylanilide hydroxamic acid (SAHA) and romidepsin, have
      been recently approved for cancer treatment. Because the screening and detailed
      characterization of HDAC inhibitors has been time-consuming, we synthesized
      coumarin-SAHA (c-SAHA) as a fluorescent probe for determining the binding
      affinities (K(d)) and the dissociation off-rates (k(off)) of the enzyme-inhibitor
      complexes. The determination of the above parameters relies on the changes in the
      fluorescence emission intensity (lambda(ex)=325 nm, lambda(em)=400 nm) of c-SAHA
      due to its competitive binding against other HDAC inhibitors, and such
      determination neither requires employment of polarization accessories nor is
      dependent on the fluorescence energy transfer from the enzyme's tryptophan
      residues to the probe. Our highly sensitive and robust analytical protocol
      presented here is applicable to most of the HDAC isozymes, and it can be easily
      adopted in a high-throughput mode for screening the HDAC inhibitors as well as
      for quantitatively determining their K(d) and k(off) values.

PMID- 20816744
TI  - A high-performance liquid chromatography assay for quantification of cardiac
      myosin heavy chain isoform protein expression.
AB  - Stress signaling in the myocardium results in enhanced expression of fetal beta
      myosin heavy chain (beta-MyHC) and reduced expression of adult alpha-myosin heavy
      chain (alpha-MyHC), with the net outcome of diminished myofibrillar ATPase
      activity and impaired contractility. Pharmacological approaches aimed at
      preventing this myosin isoform "switch" could provide therapeutic benefit to
      patients with heart failure. Myosin isoform protein expression is typically
      quantified using gel electrophoresis methods, which are time-consuming and prone
      to variability. Here we describe a facile, reversed-phase high-performance liquid
      chromatography (HPLC) method for rapidly determining the relative amounts of full
      length alpha- and beta-MyHC in rat hearts. The assay was validated using cardiac
      tissues from rats in which a key transcriptional regulator of MyHC expression,
      the thyroid hormone receptor, was pharmacologically manipulated. This novel assay
      should facilitate drug discovery efforts focused on the MyHC axis.

PMID- 20816745
TI  - Effect of khat chewing on periodontal pathogens in subgingival biofilm from
      chronic periodontitis patients.
AB  - AIMS: Existing in vitro and in vivo data suggest that khat may have a favorable
      effect on periodontal microbiota. The purpose of this study was to assess the
      effect of khat chewing on major periodontal pathogens in subgingival plaque
      samples from subjects with chronic periodontitis. MATERIALS AND METHODS: 40
      subgingival plaque samples were obtained from periodontitis and healthy sites of
      10 khat chewers (40 y median age) and 10 khat non-chewers (37.5 y median age)
      with chronic periodontitis. Absolute and relative counts of 6 periodontal
      pathogens were determined in each sample using highly sensitive and specific
      Taqman real-time PCR assays. Data were analyzed using an ordinal regression
      model. RESULTS: Significantly more total bacteria were detected in samples from
      the periodontitis sites of the khat chewers (OR=20). Treponema denticola was
      present at significantly higher absolute counts at the healthy as well as
      periodontitis sites of the khat chewers (OR=3.13 and 13, respectively). However,
      the khat chewers harbored significantly lower absolute counts of Porphyromonas
      gingivalis at the healthy sites (OR=0.07). Furthermore, khat chewing was
      significantly associated with lower relative counts of Porphyromonas gingivalis,
      fusobacterium ssp., prevotella ssp. and Parvimonas micra-like species in
      subgingival plaque samples from both healthy and periodontitis sites (OR=0.11
      0.33). Only Treponema denticola was found in higher relative counts at the
      healthy sites of the khat chewers (OR=2.98). CONCLUSIONS: Overall, there was a
      lower burden of pathogens in the khat chewers. Findings from the current study
      are suggestive of a potential prebiotic effect for khat on periodontal
      microbiota.

PMID- 20816746
TI  - Structural biology of redox partner interactions in P450cam monooxygenase: a
      fresh look at an old system.
AB  - The P450cam monooxygenase system consists of three separate proteins: the FAD
      containing, NADH-dependent oxidoreductase (putidaredoxin reductase or Pdr),
      cytochrome P450cam and the 2Fe2S ferredoxin (putidaredoxin or Pdx), which
      transfers electrons from Pdr to P450cam. Over the past few years our lab has
      focused on the interaction between these redox components. It has been known for
      some time that Pdx can serve as an effector in addition to its electron shuttle
      role. The binding of Pdx to P450cam is thought to induce structural changes in
      the P450cam active site that couple electron transfer to substrate hydroxylation.
      The nature of these structural changes has remained unclear until a particular
      mutant of P450cam (Leu358Pro) was found to exhibit spectral perturbations similar
      to those observed in wild type P450cam bound to Pdx. The crystal structure of the
      L358P variant has provided some important insights on what might be happening
      when Pdx docks. In addition to these studies, many Pdx mutants have been analyzed
      to identify regions important for electron transfer. Somewhat surprisingly, we
      found that Pdx residues predicted to be at the P450cam-Pdx interface play
      different roles in the reduction of ferric P450cam and the ferrous P450-O(2)
      complex. More recently we have succeeded in obtaining the structure of a
      chemically cross-linked Pdr-Pdx complex. This fusion protein represents a valid
      model for the noncovalent Pdr-Pdx complex as it retains the redox activities of
      native Pdr and Pdx and supports monooxygenase reactions catalyzed by P450cam. The
      insights gained from these studies will be summarized in this review.

PMID- 20816747
TI  - Kinetic evidence that allosteric activation of antithrombin by heparin is
      mediated by two sequential conformational changes.
AB  - The serpin, antithrombin, requires allosteric activation by a sequence-specific
      pentasaccharide unit of heparin or heparan sulfate glycosaminoglycans to function
      as an anticoagulant regulator of blood clotting proteases. Surprisingly, X-ray
      structures have shown that the pentasaccharide produces similar induced-fit
      changes in the heparin binding site of native and latent antithrombin despite
      large differences in the heparin affinity and global conformation of these two
      forms. Here we present kinetic evidence for similar induced-fit mechanisms of
      pentasaccharide binding to native and latent antithrombins and kinetic
      simulations which together support a three-step mechanism of allosteric
      activation of native antithrombin involving two successive conformational
      changes. Equilibrium binding studies of pentasaccharide interactions with native
      and latent antithrombins and the salt dependence of these interactions suggest
      that each conformational change is associated with distinct spectroscopic changes
      and is driven by a progressively better fit of the pentasaccharide in the binding
      site. The observation that variant antithrombins that cannot undergo the second
      conformational change bind the pentasaccharide like latent antithrombin and are
      partially activated suggests that both conformational changes contribute to
      allosteric activation, in agreement with a recently proposed model of allosteric
      activation.

PMID- 20816748
TI  - C-terminal region of USP7/HAUSP is critical for deubiquitination activity and
      contains a second mdm2/p53 binding site.
AB  - USP7, also known as the hepes simplex virus associated ubiquitin-specific
      protease (HAUSP), deubiquitinates both mdm2 and p53, and plays an important role
      in regulating the level and activity of p53. Here, we report that deletion of the
      TRAF-like domain at the N-terminus of USP7, previously reported to contain the
      mdm2/p53 binding site, has no effect on USP7 mediated deubiquitination of Ub(n)
      mdm2 and Ub(n)-p53. Amino acids 208-1102 were identified to be the minimal length
      of USP7 that retains proteolytic activity, similar to full length enzyme, towards
      not only a truncated model substrate Ub-AFC, but also Ub(n)-mdm2, Ub(n)-p53. In
      contrast, the catalytic domain of USP7 (amino acids 208-560) has 50-700 fold less
      proteolytic activity towards different substrates. Moreover, inhibition of the
      catalytic domain of USP7 by Ubal is also different from the full length or TRAF
      like domain deleted proteins. Using glutathione pull-down methods, we demonstrate
      that the C-terminal domain of USP7 contains additional binding sites, a.a. 801
      1050 and a.a. 880-1050 for mdm2 and p53, respectively. The additional USP7
      binding site on mdm2 is mapped to be the C-terminal RING finger domain (a.a. 425
      491). We propose that the C-terminal domain of USP7 is responsible for
      maintaining the active conformation for catalysis and inhibitor binding, and
      contains the prime side of the proteolytic active site.

PMID- 20816750
TI  - Fibronectin and vitronectin induce AP-1-mediated matrix metalloproteinase-9
      expression through integrin alpha(5)beta(1)/alpha(v)beta(3)-dependent Akt, ERK
      and JNK signaling pathways in human umbilical vein endothelial cells.
AB  - The activity of matrix metalloproteinases (MMPs), which selectively degrades the
      extracellular matrix (ECM), is critical in angiogenesis. Conversely, changes in
      ECM composition/structure alter the expression and activity of MMPs in various
      cell types. In the present study, we examined whether changes in ECM composition
      affect MMPs expression/activity of endothelial cells and thereby alter the
      surrounding ECM structure. Among the ECM molecules examined, fibronectin (FN) and
      vitronectin (VN) increased the expression and activity of MMP-9 in human
      umbilical vein endothelial cells (HUVECs). Both alpha(5)beta(1) and
      alpha(v)beta(3) integrins were involved in FN-induced MMP-9 expression. Also, FN
      induced MMP-9 expression was found to be mediated by AP-1 transcription factors,
      including c-Jun, JunB, and JunD. Inhibitors or siRNAs specific to AP-1 activating
      signal transducers, including FAK-Src, PI3K/Akt, ERK, and JNK, abolished both FN
      induced AP-1 activation and MMP-9 expression. VN-induced AP-1 activation and MMP
      9 expression were also mediated by these AP-1 activating signal transducers in
      addition to p38 MAPK. Moreover, treatment with FN or VN resulted in increased
      degradation of collagen on HUVEC culture plates. Taken together, our data suggest
      that both fibronectin and vitronectin induce MMP-9 expression via the AP-1
      activating signaling pathways in endothelial cells, and thereby stimulate
      degradation of surrounding collagen, leading to alterations in ECM structure and
      potentially the promotion of angiogenesis.

PMID- 20816751
TI  - Over-expression of Tfam improves the mitochondrial disease phenotypes in a mouse
      model system.
AB  - The phenotypes of mitochondrial diseases caused by mutations in mitochondrial DNA
      (mtDNA) have been proposed to be strictly regulated by the proportion of wild
      type and pathogenically mutated mtDNAs. More specifically, it is thought that the
      onset of the disease phenotype occurs when cells cannot maintain the proper
      mitochondrial function because of an over-abundance of pathological mtDNA.
      Therapies that cause a decrease in the pathogenic mtDNA population have been
      proposed as a treatment for mitochondrial diseases, but these therapies are
      difficult to apply in practice. In this report, we present a novel concept: to
      improve mitochondrial disease phenotypes via an increase in the absolute copy
      number of the wild-type mtDNA population in pathogenic cells even when the
      relative proportion of mtDNA genotypes remains unchanged. We have succeeded in
      ameliorating the typical symptoms of mitochondrial disease in a model mouse line
      by the over-expression of the mitochondrial transcription factor A (Tfam)
      followed by an increase of the mtDNA copy number. This new concept should lead to
      the development of a novel therapeutic treatment for mitochondrial diseases.

PMID- 20816749
TI  - Role of sympathetic nervous system in the entrainment of circadian natural-killer
      cell function.
AB  - Previous research in our laboratory has demonstrated robust circadian variations
      of cytokines and cytolytic factors in enriched NK cells from rat spleen, strongly
      suggesting these functions may be subject to circadian regulation. The SCN
      mediates timing information to peripheral tissues by both humoral and neural
      inputs. In particular, noradrenergic (NE) sympathetic nervous system (SNS)
      terminals innervate the spleen tissue communicating information between central
      and peripheral systems. However, whether these immune factors are subject to
      timing information conveyed through neural NE innervation to the spleen remained
      unknown. Indeed, we were able to characterize a circadian rhythm of NE content in
      the spleen, supporting the role of the SNS as a conveyor of timing information to
      splenocytes. By chemically producing a local splenic sympathectomy through
      guanethidine treatment, the splenic NE rhythm was abolished or shifted as
      indicated by a blunting of the expected peak at ZT7. Consequently, the daily
      variations of cytokine, TNF-alpha, and cytolytic factors, granzyme-B and
      perforin, in NK cells and splenocytes were altered. Only time-dependent mRNA
      expression of IFN-gamma was altered in splenocytes, but not protein levels in NK
      cells, suggesting non-neural entrainment cues may be necessary to regulate
      specific immune factors. In addition, the rhythms of clock genes and proteins,
      Bmal1 and Per2, in these tissues also displayed significantly altered daily
      variations. Collectively, these results demonstrate rhythmic NE input to the
      spleen acts as an entrainment cue to modulate the molecular clock in NK cells and
      other spleen cells possibly playing a role in regulating the cytokine and
      cytolytic function of these cells.

PMID- 20816752
TI  - 2-Methoxy-4-vinylphenol can induce cell cycle arrest by blocking the hyper
      phosphorylation of retinoblastoma protein in benzo[a]pyrene-treated NIH3T3 cells.
AB  - Benzo[a]pyrene (BaP) is an environment carcinogen that can enhance cell
      proliferation by disturbing the signal transduction pathways in cell cycle
      regulation. In this study, the effects of 2M4VP on cell proliferation, cell cycle
      and cell cycle regulatory proteins were studied in BaP-treated NIH 3T3 cells to
      establish the molecular mechanisms of 2M4VP as anti-proliferative agents. 2M4VP
      exerted a dose-dependent inhibitory effect on cell growth correlated with a G1
      arrest. Analysis of G1 cell cycle regulators expression revealed 2M4VP increased
      expression of CDK inhibitor, p21Waf1/Cip1 and p15 INK4b, decreased expression of
      cyclin D1 and cyclin E, and inhibited kinase activities of CDK4 and CDK2.
      However, 2M4VP did not affect the expression of CDK4 and CDK2. Also, 2M4VP
      inhibited the hyper-phosphorylation of Rb induced by BaP. Our results suggest
      that 2M4VP induce growth arrest of BaP-treated NIH 3T3 cells by blocking the
      hyper-phosphorylation of Rb via regulating the expression of cell cycle-related
      proteins.

PMID- 20816753
TI  - AS1907417, a novel GPR119 agonist, as an insulinotropic and beta-cell
      preservative agent for the treatment of type 2 diabetes.
AB  - G-protein-coupled receptor (GPR) 119 is involved in glucose-stimulated insulin
      secretion (GSIS) and represents a promising target for the treatment of type 2
      diabetes as it is highly expressed in pancreatic beta-cells. Although a number of
      oral GPR119 agonists have been developed, their inability to adequately directly
      preserve beta-cell function limits their effectiveness. Here, we evaluated the
      therapeutic potential of a novel small-molecule GPR119 agonist, AS1907417, which
      represents a modified form of a 2,4,6-tri-substituted pyrimidine core agonist,
      AS1269574, we previously identified. The exposure of HEK293 cells expressing
      human GPR119, NIT-1 cells expressing human insulin promoter, and the pancreatic
      beta-cell line MIN-6-B1 to AS1907417, enhanced intracellular cAMP, GSIS, and
      human insulin promoter activity, respectively. In in vivo experiments involving
      fasted normal mice, a single dose of AS1907417 improved glucose tolerance, but
      did not affect plasma glucose or insulin levels. Twice-daily doses of AS1907417
      for 4weeks in diabetic db/db, aged db/db mice, ob/ob mice, and Zucker diabetic
      fatty rats reduced hemoglobin A1c levels by 1.6%, 0.8%, 1.5%, and 0.9%,
      respectively. In db/db mice, AS1907417 improved plasma glucose, plasma insulin,
      pancreatic insulin content, lipid profiles, and increased pancreatic insulin and
      pancreatic and duodenal homeobox 1 (PDX-1) mRNA levels. These data demonstrate
      that novel GPR119 agonist AS1907417 not only effectively controls glucose levels,
      but also preserves pancreatic beta-cell function. We therefore propose that
      AS1907417 represents a new type of antihyperglycemic agent with promising
      potential for the effective treatment of type 2 diabetes.

PMID- 20816754
TI  - Calcium and secondary CPK signaling in plants in response to herbivore attack.
AB  - Plant Ca(2+) signals are involved in a sizable array of intracellular signaling
      pathways after pest invasion. Upon herbivore feeding there is a dramatic Ca(2+)
      influx, followed by the activation of Ca(2+)-dependent signal transduction
      pathways that include interacting downstream networks of kinases for defense
      responses. Notably, Ca(2+)-binding sensory proteins such as Ca(2+)-dependent
      protein kinases (CPKs) have recently been documented to mediate the signaling
      following Ca(2+) influx after herbivory, in phytohormone-independent manners.
      Here, we review the sequence of signal transductions triggered by herbivory
      evoked Ca(2+) signaling leading to CPK actions for defense responses, and discuss
      in a comparative way the involvement of CPKs in the signal transduction of a
      variety of other biotic and abiotic stresses.

PMID- 20816755
TI  - Repetitive exposure to a 60-Hz time-varying magnetic field induces DNA double
      strand breaks and apoptosis in human cells.
AB  - We investigated the effects of extremely low frequency time-varying magnetic
      fields (MFs) on human normal and cancer cells. Whereas a single exposure to a 60
      Hz time-varying MF of 6mT for 30min showed no effect, repetitive exposure
      decreased cell viability. This decrease was accompanied by phosphorylation of
      gamma-H2AX, a common DNA double-strand break (DSB) marker, and checkpoint kinase
      2 (Chk2), which is critical to the DNA damage checkpoint pathway. In addition,
      repetitive exposure to a time-varying MF of 6mT for 30min every 24h for 3days led
      to p38 activation and induction of apoptosis in cancer and normal cells.
      Therefore, these results demonstrate that repetitive exposure to MF with
      extremely low frequency can induce DNA DSBs and apoptosis through p38 activation.
      These results also suggest the need for further evaluation of the effects of
      repetitive exposure to environmental time-varying MFs on human health.

PMID- 20816756
TI  - Genetic tracing of the neural pathway for bitter taste in t2r5-WGA transgenic
      mice.
AB  - To visualize the neural pathways originating from bitter taste receptor cells
      (TRCs), we generated transgenic mice expressing the transneuronal tracer wheat
      germ agglutinin (WGA) under the control of the mouse T2R5 gene promoter/enhancer
      (t2r5-WGA mice). WGA mRNA was specifically expressed in bitter TRCs. The WGA
      protein was detected in bitter TRCs and nerve processes in taste buds, but not in
      sweet, umami, or sour TRCs. The WGA protein was transferred to a subset of
      sensory neurons in the geniculate and nodose/petrosal ganglia. These results
      suggest that bitter TRCs, which are devoid of synaptic structures, are innervated
      by gustatory neurons and that bitter sensory information is directly transmitted
      to specific gustatory neurons. The t2r5-WGA mice provide a useful tool for
      identifying gustatory relay neurons in the peripheral sensory ganglia responsible
      for aversive sensations.

PMID- 20816757
TI  - Preparation and solid state characterisation of chlorothiazide sodium
      intermolecular self-assembly suprastructure.
AB  - Chlorothiazide (CTZ), unlike other thiazide diuretics, can form salts. An
      injectable formulation containing the sodium salt is available; however neither
      the physicochemical characteristics of the salt nor its solid state form have
      been previously reported. This work reports on the crystal structure of
      chlorothiazide sodium. The structure was investigated by single crystal X-ray and
      nuclear magnetic spectroscopy (NMR) analyses and compared to chlorothiazide,
      while the solid state characteristics were assessed by thermal analysis, powder X
      ray diffraction, infrared spectroscopy, dynamic moisture sorption and solubility
      analysis. The crystal structure of chlorothiazide sodium was determined to be
      triclinic; the crystal space group type was P-1. Chlorothiazide sodium presented
      a self-assembly polymeric-type suprastucture, where the unit cell comprised two
      chlorothiazide molecules bonded together with sodium cations through the water
      bridges. The coordinate centre comprised the following:
      (CTZ)(3).(H(2)O).Na(H(2)O)(2)Na.(H(2)O).(CTZ)(3). The crystalline material was
      determined to be a monosodium dihydrate, stable in the range of 10-90% relative
      humidity (RH) at 25 degrees C. Additional processing of the salt resulted in a
      crystalline anhydrous form which was stable in the range 0-20% RH at 25 degrees
      C. The aqueous solubility of the chlorothiazide sodium dihydrate at 37 degrees C
      was found to be approximately 400-fold higher than that of chlorothiazide, which
      may present biopharmaceutical advantages for the salt compared to the non-salt
      form.

PMID- 20816758
TI  - Abnormal cell patterning at the cortical gray-white matter boundary in autism
      spectrum disorders.
AB  - Previous research on neuronal spacing and columnar organization indicates the
      presence of cell patterning alterations within the cerebral cortex of individuals
      with autism spectrum disorders (ASD). These patterning abnormalities include
      irregularities at the gray-white matter boundary and may implicate early
      neurodevelopmental events such as migration in altering cortical organization in
      ASD. The present study utilized a novel method to quantify the gray-white matter
      boundary in eight ASD and eight typically developing control subjects. Digital
      photomicrographs of the gray-white matter boundary were acquired from multiple
      positions within the superior temporal gyrus (BA21), dorsolateral frontal lobe
      (BA9), and dorsal parietal lobe (BA7) of each case. A sigmoid curve was fitted to
      the transition zone between layer VI and underlying white matter (subplate), and
      the slope of the resulting curve was used as a measure of the spatial extent of
      the transition zone. For all three cortical regions examined, ASD subjects showed
      "shallower" sigmoid curves compared to neurotypicals, indicating the presence of
      an indistinct boundary between cortical layer VI and the underlying white matter.
      These results may reflect the presence of supernumerary neurons beneath the
      cortical plate that could be the result of migration deficits or failed apoptosis
      in the subplate region. Furthermore, these findings raise questions regarding the
      validity of cortical measures that rely on gray-white matter parcellation, since
      an indistinct transition zone could lead to a misplaced cortical boundary and
      errors in both thickness and volume measures.

PMID- 20816760
TI  - Multiple ways to the prior occurrence of an event: an electrophysiological
      dissociation of experimental and conceptually driven familiarity in recognition
      memory.
AB  - Recent research has shown that familiarity contributes to associative memory when
      the to-be-associated stimuli are unitized during encoding. However, the specific
      processes underlying familiarity-based recognition of unitized representations
      are still indefinite. In this study, we present electrophysiologically
      dissociable early old/new effects, presumably related to two different kinds of
      familiarity inherent in associative recognition tasks. In a study-test
      associative recognition memory paradigm, we employed encoding conditions that
      established unitized representations of two pre-experimentally unrelated words,
      e.g. vegetable-bible. We compared event-related potentials (ERP) during the
      retrieval of these unitized word pairs using different retrieval cues. Word pairs
      presented in the same order as during unitization at encoding elicited a
      parietally distributed early old/new effect which we interpret as reflecting
      conceptually driven familiarity for newly formed concepts. Conversely, word pairs
      presented in reversed order only elicited a topographically dissociable early
      effect, i.e. the mid-frontal old/new effect, the putative correlate of
      experimental familiarity. The late parietal old/new effect, the putative ERP
      correlate of recollection, was obtained irrespective of word order, though it was
      larger for words presented in same order. These results indicate that familiarity
      may not be a unitary process and that different task demands can promote the
      assessment of conceptually driven familiarity for novel unitized concepts or
      experimentally-induced increments of experimental familiarity, respectively.

PMID- 20816759
TI  - Perception of a Japanese vowel length contrast by Japanese and American English
      listeners: behavioral and electrophysiological measures.
AB  - This study examined the role of automatic selective perceptual processes in
      native and non-native listeners' perception of a Japanese vowel length contrast
      (tado vs. taado), using multiple, natural-speech tokens of each category as
      stimuli in a "categorial oddball" design. Mismatch negativity (MMN) was used to
      index discrimination of the temporally-cued vowel contrast by naive adult
      American listeners and by a native Japanese-speaking control group in two
      experiments in which attention to the auditory input was manipulated: in Exp 1
      (Visual-Attend), listeners silently counted deviants in a simultaneously
      presented visual categorial oddball shape discrimination task; in Exp 2 (Auditory
      Attend), listeners attended to the auditory input and implicitly counted target
      deviants. MMN results showed effects of language experience and attentional
      focus: MMN amplitudes were smaller for American compared to Japanese listeners in
      the Visual-Attend Condition and for the American listeners in the Visual compared
      to Auditory-Attend Condition. Subtle differences in topography were also seen,
      specifically in that the Japanese group showed more robust responses than the
      American listeners at left hemisphere scalp sites that probably index activity
      from the superior temporal gyrus. Follow-up behavioral discrimination tests
      showed that Americans discriminated the contrast well above chance, but more
      poorly than did Japanese listeners. This pattern of electrophysiological and
      behavioral results supports the conclusion that early experience with phonetic
      contrasts of a language results in changes in neural representations in the
      auditory cortex that allow for more robust automatic, phonetic processing of
      native-language speech input.

PMID- 20816761
TI  - Implantation of adult bone marrow-derived mesenchymal stem cells transfected with
      the neurotrophin-3 gene and pretreated with retinoic acid in completely
      transected spinal cord.
AB  - Implantation of marrow-derived mesenchymal stem cells (MSCs) is the most
      promising therapeutic strategy for the treatment of spinal cord injury (SCI),
      especially because of their potential for clinical application, such as the
      avoidance of immunologic rejection, their strong secretory properties, and their
      plasticity for developing into neural cells. However, the recovery from SCI after
      MSC implantation is minimal due to their limited capacity for the reduction of
      cystic cavitation, for the axonal regeneration and their uncertain neural
      plasticity in the spinal cord. We previously pretreated MSCs with all-trans
      retinoic acid (RA) in vitro. Then we genetically modified them to overexpress
      neurotrophin-3 (NT-3) via a recombinant adenoviral vector (Adv). This combined
      treatment not only permitted more neuronal differentiation of MSCs, but
      stimulated more NT-3 secretion prior to grafting, according to our previous and
      present results. When these cells were implanted into the transected spinal cord
      of rats, the animals had some improvement (both functionally and structurally),
      including the recovery of hindlimb locomotor function, shown by the highest
      Basso, Beattie, and Bresnahan (BBB) scores, as well as dramatically reduced
      cavity volume, clear axonal regeneration and more neuronal survival. In contrast,
      simple MSC implantation is not a very effective therapy for spinal transection.
      However, the neuronal differentiation of MSCs after treatment with a combination
      of Adv-mediated NT-3 gene transfer and RA was only mildly improved in vivo.

PMID- 20816762
TI  - Oxidative stress: a potential recipe for anxiety, hypertension and insulin
      resistance.
AB  - We recently reported involvement of oxidative stress in anxiety-like behavior of
      rats. Others in separate studies have demonstrated a link between oxidative
      stress and hypertension as well as with type 2 diabetes/insulin resistance. In
      the present study, we have tested a putative role of oxidative stress in anxiety
      like behavior, hypertension and insulin resistance using a rat model of oxidative
      stress. Oxidative stress in rats was produced by xanthine (0.1%; drinking water)
      and xanthine oxidase (5 U/kg; i.p.). X+XO-treated rats had increased plasma and
      urinary 8-isoprostane levels (a marker of oxidative stress) and increased
      malondialdehyde (MDA) levels in the hippocampus and amygdala as compared to
      control rats. Serum corticosterone (a systemic marker of stress and anxiety)
      levels also increased with X+XO treatment. Moreover, anxiety-like behavior
      measured via open-field and light-dark exploration behavior tests significantly
      increased in X+XO-treated rats. Mean arterial blood pressure measured in
      anesthetized rats increased in X+XO-treated compared to control rats.
      Furthermore, plasma insulin but not glucose levels together with homeostasis
      model assessment (HOMA), an index of insulin resistance, were higher in X+XO
      treated rats. Our studies suggest that oxidative stress is a common factor that
      link anxiety-like behavior, hypertension and insulin resistance in rats.

PMID- 20816763
TI  - Neural development of methyl-CpG-binding protein 2 null embryonic stem cells: a
      system for studying Rett syndrome.
AB  - Mutations in methyl-CpG-binding protein 2 (MeCP2) gene cause the
      neurodevelopmental disorder Rett syndrome (RTT). Here, we describe a new
      experimental system that efficiently elucidates the role of MeCP2 in neural
      development. MeCP2-null and control ES cells were generated by adenoviral
      conditional targeting and examined for maintenance of the undifferentiated ES
      cell state, neurogenesis, and gliogenesis during in vitro differentiation. In
      addition, dopamine release and electrophysiological features of neurons
      differentiated from these ES cells were examined. Loss of MeCP2 did not affect
      undifferentiated ES cell colony morphology and growth, or the timing or
      efficiency of neural stem cell differentiation into Nestin-, TuJ- or TH-positive
      neurons. In contrast, gliogenesis was drastically accelerated by MeCP2
      deficiency. Dopamine production and release in response to a depolarizing
      stimulus in MeCP2-null ES-derived dopaminergic neurons was intact. However, MeCP2
      null differentiated neurons showed significantly smaller voltage-dependent Na(+)
      currents and A-type K(+) currents, suggesting incomplete maturation. Thus, MeCP2
      is not essential for maintenance of the undifferentiated ES cell state,
      neurogenesis, or dopaminergic function; rather, it is principally involved in
      inhibiting gliogenesis. Altered neuronal maturity may indirectly result from
      abnormal glial development and may underlie the pathogenesis of RTT. These data
      contribute to a better understanding of the developmental roles of MeCP2 and the
      pathogenesis of RTT.

PMID- 20816764
TI  - Contributions of dorsal root reflex and axonal reflex to formalin-induced
      inflammation.
AB  - The dorsal root reflex (DRR) and the axonal reflex (AR) are antidromic activities
      in primary afferents and are involved in neurogenic inflammation. DRRs and/or ARs
      lead to release of neuropeptides calcitonin gene-related peptide (CGRP) and
      substance P (SP). CGRP causes blood vessels to dilate leading to an increase in
      blood perfusion, whereas SP causes plasma extravasation, leading to edema. Both
      DRR and AR can be evoked by noxious stimuli. The goal of this study was to
      determine the role of DRR and AR in neurogenic inflammation by examining the
      blood perfusion (BP) change in hindpaws in response to formalin injection (an
      acute inflammatory agent). Laser Doppler images were collected simultaneously in
      both hindpaws in anesthetized rats to determine the level of BP. Local lidocaine
      was applied to the left sciatic nerve to block both orthodromic signals and
      antidromic DRRs without affecting ARs. All rats then received a subcutaneous
      formalin injection to the left hindpaw. Our results showed that (1) the mean BP
      of the left paw increased significantly following formalin injection, with or
      without lidocaine; (2) application of lidocaine in the left sciatic nerve alone
      significantly increased BP ipsilaterally; (3) formalin injection following
      lidocaine application significantly increased BP more than the group without
      lidocaine; and (4) there was delayed significant BP increase in the right
      (contralateral) hindpaw following formalin injection with or without lidocaine.
      It is concluded that ARs play a more important role than DRRs in formalin-induced
      neurogenic inflammation.

PMID- 20816766
TI  - Acute MDMA administration alters the distribution and circadian rhythm of wheel
      running activity in the rat.
AB  - Ecstasy users report a number of adverse events following use including disturbed
      sleep. Previous research has suggested that MDMA affects the circadian system,
      however, the acute effects following a single, moderate dose have not been well
      characterised. The current study investigated how MDMA affected the circadian
      system, as measured by the amount and temporal distribution of wheel-running
      activity in male rats (n=90), housed individually under a 12-12 h light-dark (LD)
      cycle prior to treatment. MDMA (5 or 10 mg/kg) or saline was administered in a
      single i.p. injection during the light phase of the LD cycle and post-treatment
      activity was monitored during subsequent LD cycles (Experiment 1), or under
      constant darkness (Experiment 2). MDMA treatment disrupted wheel running activity
      in both experimental paradigms. In Experiment 1, 10 mg/kg MDMA significantly
      increased the amount of activity during the rest phase on the day of treatment
      and 1-day post treatment. This was accompanied by a change in the distribution of
      activity across the LD cycle during the first 24 h period after treatment,
      without a change in the overall daily activity level. Experiment 2 found that
      MDMA affected the circadian system as reflected by changes in the duration of the
      active phase, tau and activity offset. As a single dose of MDMA was able to
      disrupt the circadian rhythmicity of locomotor activity, this finding has
      implications for other behaviours that are under circadian control including the
      sleep/wake cycle.

PMID- 20816765
TI  - Regulation of endogenous conductances in GnRH neurons by estrogens.
AB  - 17beta-estradiol (E2) regulates the activity of the gonadotropin-releasing
      hormone (GnRH) neurons through both presynaptic and postsynaptic mechanisms, and
      this ovarian steroid hormone is essential for cyclical GnRH neuronal activity and
      secretion. E2 has significant actions to modulate the mRNA expression of numerous
      ion channels in GnRH neurons and/or to enhance (suppress) endogenous conductances
      (currents) including potassium (K(ATP), A-type) and calcium low voltage T-type
      and high voltage L-type currents. Also, it is well documented that E2 can alter
      the excitability of GnRH neurons via direct action, but the intracellular
      signaling cascades mediating these actions are not well understood. As an
      example, K(ATP) channels are critical ion channels needed for maintaining GnRH
      neurons in a hyperpolarized state for recruiting T-type calcium channels that are
      important for burst firing in GnRH neurons. E2 modulates the activity of K(ATP)
      channels via a membrane-initiated signaling pathway in GnRH neurons. Obviously
      there are other channels, including the small conductance activated K(+) (SK)
      channels, that maybe modulated by this signaling pathway, but the ensemble of mER
      , ERalpha-, and ERbeta-mediated effects both pre- and post-synaptic will
      ultimately dictate the excitability of GnRH neurons.

PMID- 20816767
TI  - Pharmacological characterization of [(125)I]CHIBA-1006 binding, a new radioligand
      for alpha7 nicotinic acetylcholine receptors, to rat brain membranes.
AB  - The alpha7 nicotinic acetylcholine receptors (nAChRs) play an important role in
      the pathophysiology of neuropsychiatric diseases such as schizophrenia and
      Alzheimer's disease. However, there are currently no suitable small molecule
      radioligands for imaging alpha7 nAChRs in the brain. In this study, we
      synthesized the novel radioligand [(125)I]4-iodophenyl 1,4
      diazaicyclo[3.2.2]nonane-4-carboxylate ([(125)I]CHIBA-1006), a iodine-derivative
      of the selective alpha7 nAChR agonist SSR180711, and studied the characterization
      of [(125)I]CHIBA-1006 binding to rat brain membranes. The assays of [(125)I]CHIBA
      1006 binding to rat brain membranes were performed at 4 degrees C. The presence
      of a single saturable high-affinity binding component for [(125)I]CHIBA-1006 in
      the rat brain was shown. Scatchard analysis revealed an apparent equilibrium
      dissociation constant (K(d)) of 88.2+/-21.4nM and a maximal number of binding
      sites (B(max)) of 65.4+/-6.8fmol/mg protein (mean+/-SEM, n=4). The specific
      binding of [(125)I]CHIBA-1006 was inhibited by a number of alpha7 nAChR-selective
      ligands (e.g., unlabeled CHIBA-1006, SSR180711, CHIBA-1001, MG624 and A844606),
      suggesting a similarity among alpha7 nAChR pharmacological profiles. In contrast,
      alpha-bungarotoxin, MLA, and nicotine showed very weak affinity for [(125)I]CHIBA
      1006 binding. The regional distribution of [(125)I]CHIBA-1006 binding to crude
      membranes from dissected regions of the rat brain was different from that of
      [(125)I]alpha-bungarotoxin binding, suggesting that [(125)I]CHIBA-1006 binding
      sites may not be identical to [(125)I]alpha-bungarotoxin binding sites in the rat
      brain. The present findings suggest that [(125)I]CHIBA-1006 would be a useful new
      small molecule radioligand for alpha7 nAChRs in the brain.

PMID- 20816768
TI  - Adolescent brain development, risk-taking and vulnerability to addiction.
AB  - Adolescents (12-18 years old) and young adults (18-25 years old), are more likely
      than older adults to drive-or agree to be driven-recklessly or while intoxicated,
      to use illicit or dangerous substances and to engage in both minor and more
      serious antisocial behaviour. Numerous factors during adolescence may lead to or
      favour initiation of drug use, such as sensation-seeking, gregariousness and
      social conformity. These aspects, however, cannot be dissociated from the
      increased sex drive and quest for an integrated self. In the separation
      individuation process, relationships with peers play many different roles: a
      field for experimentation, emotional support, a place for "projection" and
      "identification", and the possibility of finding a partner. Unsurprisingly,
      therefore, drug use generally takes place in a group setting. Despite evidence of
      heightened real-world risk-taking, laboratory studies have yet to yield
      consistent evidence that adolescents, when on their own, are more inclined
      towards risky behaviour than their elders. Moreover, their comprehension and
      reasoning abilities in risky decision-making situations are roughly equivalent to
      those of adults. Structural and functional neuroimaging studies have shown that
      neural circuitry undergoes major reorganization during adolescence, particularly
      in those regions of the brain relating to executive functions, the self and
      social cognition, and that the "emotional brain" may play a role in that
      reorganization. Age-related decreases in gray matter volume mainly reflect a
      reduction in the number of synapses and the complexity of axonal ramifications.
      By 18-20 years old, most of the subcortical white matter and association pathways
      have reached a plateau. Risk-taking behavior and novelty-seeking may provide,
      with an appropriate feed back, a mechanism to optimize brain development in
      adolescence.

PMID- 20816769
TI  - Environment, genes, and experience: lessons from behavior genetics.
AB  - The article reviews the theoretical analysis of the problems inherent in studying
      the environment within behavior genetics across several periods in the
      development of environmental studies in behavior genetics and proposes some
      possible alternatives to traditional approaches to studying the environment in
      behavior genetics. The first period (from the end of the 1920s to the end of the
      1970s), when the environment was not actually studied, is called pre
      environmental; during this time, the basic principles and theoretical models of
      understanding environmental effects in behavior genetics were developed. The
      second period is characterized by the development of studies on environmental
      influences within the traditional behavior genetics paradigm; several approaches
      to studying the environment emerged in behavior genetics during this period, from
      the beginning of the 1980s until today. At the present time, the field is
      undergoing paradigmatic changes, concerned with methodology, theory, and
      mathematical models of genotype-environment interplay; this might be the
      beginning of a third period of development of environmental studies in behavior
      genetics. In another part, the methodological problems related to environmental
      studies in behavior genetics are discussed. Although the methodology used in
      differential psychology is applicable for assessment of differences between
      individuals, it is insufficient to explain the sources of these differences. In
      addition, we stress that psychoanalytic studies of twins and their experiences,
      initiated in the 1930s and continued episodically until the 1980s, could bring an
      interesting methodology and contribute to the explanation of puzzling findings
      from environmental studies of behavior genetics. Finally, we will conclude with
      implications from the results of environmental studies in behavior genetics,
      including methodological issues.

PMID- 20816770
TI  - Towards an integrative neuroscientific and psychodynamic approach to the
      transmission of attachment.
AB  - Developed by Bowlby in 1969, the concept of attachment led to significant
      breakthroughs in the exploration of subjective and intersubjective developmental
      processes. Defined as an innate behavioral system that enables an infant to
      regulate his closeness to his mother, attachment lies at the crossroads of
      psychoanalytical and cognitive neuroscientific theories. Standardized instruments
      for assessing the quality of attachment helped to validate the hypothesis that a
      variety of attachment patterns exist in mother-infant dyads and are underpinned
      by mental representations known as Internal Working Models. Research has also
      shown that most of these attachment patterns are transmitted by the mother to the
      infant. These results increased researchers' interest in the concept of
      transgenerational transmission of attachment patterns that might be considered as
      a stepping stone of transgenerational transmission. Starting with hypotheses on
      the transmission of attachment, this article underlines that despite conceptual
      differences between the psychoanalytical and the developmental theories, they
      agree on the major mediating role of behaviors (micro-behaviors in situations of
      interaction) in the transgenerational transmission of attachment. Relying on the
      concept of mirror neurons and on research revealing their role in the embodied
      cognition of one's own and others' intentions, this article leads to a hypothesis
      regarding the biological mechanisms that are likely to be involved in the
      transmission of attachment. A two-stage transformation (from the mind to the body
      of/in the mother, then from the body to the mind of the infant) is hypothesized
      to occur through the embodied neurological imitation of the mirror neuron system
      and to facilitate the transmission of the attachment pattern through the same
      mechanism involved in the transmission of other significant mentalized
      representations.

PMID- 20816771
TI  - The homeostatic psyche: Freudian theory and somatic markers.
AB  - After years of reciprocal lack of interest, if not opposition, neuroscience and
      psychoanalysis are poised for a renewed dialogue. This article discusses some
      aspects of the Freudian metapsychology and its link with specific biological
      mechanisms. It highlights in particular how the physiological concept of
      homeostasis resonates with certain fundamental concepts of psychoanalysis.
      Similarly, the authors underline how the Freud and Damasio theories of brain
      functioning display remarkable complementarities, especially through their common
      reference to Meynert and James. Furthermore, the Freudian theory of drives is
      discussed in the light of current neurobiological evidences of neural plasticity
      and trace formation and of their relationships with the processes of homeostasis.
      The ensuing dynamics between traces and homeostasis opens novel avenues to
      consider inner life in reference to the establishment of fantasies unique to each
      subject. The lack of determinism, within a context of determinism, implied by
      plasticity and reconsolidation participates in the emergence of singularity, the
      creation of uniqueness and the unpredictable future of the subject. There is a
      gap in determinism inherent to biology itself. Uniqueness and discontinuity: this
      should today be the focus of the questions raised in neuroscience. Neuroscience
      needs to establish the new bases of a "discontinuous" biology. Psychoanalysis can
      offer to neuroscience the possibility to think of discontinuity. Neuroscience and
      psychoanalysis meet thus in an unexpected way with regard to discontinuity and
      this is a new point of convergence between them.

PMID- 20816772
TI  - Addressing, understanding and treating conduct disorders in adolescents through
      psychoanalysis and neuroscience: towards a disappearance of sex-differences.
AB  - Based on our findings showing that female adolescents in resident group homes
      exhibit externalized disorders at the same rate as male adolescents, explanatory
      hypotheses are developed from neuroscience (genetics and endocrinology) and from
      psychoanalysis (psychopathological and environmental approach). In particular,
      the place of the psychoanalytic approach in improving our understanding of such
      results is discussed with regard first to the clinical context and then to the
      research context. This article underlines that both approaches in psychoanalysis
      and neuroscience can, and maybe have to/should, coexist in child psychiatry.

PMID- 20816773
TI  - Psychodynamic-oriented psychological assessment predicts evolution to
      schizophrenia at 8-year follow-up in adolescents hospitalized for a manic/mixed
      episode: interest of an overall subjective rating.
AB  - Little is known concerning the prognostic significance of manic/mixed episodes in
      adolescents. In particular, whether the use of psychodynamic-oriented projective
      psychological testing predicts evolution to schizophrenia at follow-up has not
      been established. Eighty subjects, aged 12-20years old, consecutively
      hospitalized for a manic or mixed episode between 1994 and 2003 were recruited.
      All patients were contacted in 2005-2006 for a follow-up assessment. For the
      subgroup of adolescents (N=40) who had psychodynamic-oriented psychological
      testing (Rorschach and TAT), two scores regarding psychosocial risk and
      schizophrenia risk were computed using the clinical global impression (CGI)
      assessment based on an overall subjective rating given by a panel of expert
      psychologists who reviewed all protocols. At follow-up (average 8years), 25
      (62.5%) patients, 16 females and nine males, were assessed: 14 still had a
      diagnosis of bipolar disorder; eight changed to schizo-affective disorder and
      three to schizophrenia. Inter-rater reliability of both CGI-risk scores
      (psychosocial risk and schizophrenia risk) showed good clinical consensus with
      intraclass correlation and Kappa scores ranging from 0.53 to 0.75. Univariate
      analysis showed that CGI-psychosocial risk score (p=0.017), type of index episode
      (p=0.049) and CGI-schizophrenia risk score (p=0.09) were associated with
      transition to schizophrenia spectrum disorder at follow-up. Age, sex,
      socioeconomic status, duration of stay and the presence of psychotic features at
      index episode were not associated with the transition. We conclude that the CGI
      assessment appears to be valid to score risk of poor outcome using psychodynamic
      oriented psychological testing and that these scores may predict, in part, the
      transition to schizophrenia in adolescents with a history of manic/mixed episode.

PMID- 20816774
TI  - At the crossroads between psychoanalysis and neuroscience: the importance of
      subjectivity.
AB  - This paper will first advocate for a better understanding of the links between
      the psyche and the body, and also for the development of interdisciplinary
      perspectives that connect psychoanalysis and neuroscience but still respect and
      preserve the specificities of each discipline. In addition, cross-talk involves
      recognizing the incompleteness of any single discipline and allowing ourselves to
      be enriched by the differences with others through a complementary approach
      rather than a totalitarian one. Then, we will try to understand why today we find
      ourselves at the advent of the "all cerebral" era. One can think that brain
      imaging is reassuring because it gives concrete visible results, which seemingly
      brings objectivity. The danger is to set this brain indicator apart and to accord
      it scientific validity to localize brain processes on its own, without taking the
      necessary epistemological and methodological precautions; this could readily
      evoke a new form of phrenology... It seems more prudent, concerning brain-imaging
      results, to think in terms of bio-psycho-environmental interaction rather than
      linear causality. This will bring us to focus finally on subjectivity and the
      interests of taking subjectivity into account in our perception of behaviors that
      depends on relational dynamics, but also in our perception of the environment
      according to our emotions. Emotions play an important role in how we construct
      reality. They enable us to "set" events, like a fixing agent in the photo
      development process. Furthermore, the experience of an emotion or of sufficiently
      strong sensations (the threshold differs across individuals) can also trigger the
      construction of false memories with a conviction that they have really been
      experienced. The reality of our emotions does not always match the reality of
      factual events. This is a case of total subjectivity in the construction of
      reality, and illustrates the need to situate the subject within a bio-psycho
      environmental approach.

PMID- 20816775
TI  - Characterization of a beta-1,3-glucanase active in the alkaline midgut of
      Spodoptera frugiperda larvae and its relation to beta-glucan-binding proteins.
AB  - Spodoptera frugiperda beta-1,3-glucanase (SLam) was purified from larval midgut.
      It has a molecular mass of 37.5 kDa, an alkaline optimum pH of 9.0, is active
      against beta-1,3-glucan (laminarin), but cannot hydrolyze yeast beta-1,3-1,6
      glucan or other polysaccharides. The enzyme is an endoglucanase with low
      processivity (0.4), and is not inhibited by high concentrations of substrate. In
      contrast to other digestive beta-1,3-glucanases from insects, SLam is unable to
      lyse Saccharomyces cerevisae cells. The cDNA encoding SLam was cloned and
      sequenced, showing that the protein belongs to glycosyl hydrolase family 16 as
      other insect glucanases and glucan-binding proteins. Multiple sequence alignment
      of beta-1,3-glucanases and beta-glucan-binding protein supports the assumption
      that the beta-1,3-glucanase gene duplicated in the ancestor of mollusks and
      arthropods. One copy originated the derived beta-1,3-glucanases by the loss of an
      extended N-terminal region and the beta-glucan-binding proteins by the loss of
      the catalytic residues. SLam homology modeling suggests that E228 may affect the
      ionization of the catalytic residues, thus displacing the enzyme pH optimum. SLam
      antiserum reacts with a single protein in the insect midgut.
      Immunocytolocalization shows that the enzyme is present in secretory vesicles and
      glycocalyx from columnar cells.

PMID- 20816776
TI  - Comparative hypoglycemic and nephroprotective effects of tocotrienol rich
      fraction (TRF) from palm oil and rice bran oil against hyperglycemia induced
      nephropathy in type 1 diabetic rats.
AB  - Diabetic nephropathy (DN) is a serious complication confronted by patients with
      diabetes. Available data indicate that the development of DN is linked to
      hyperglycemia. Tocotrienol rich fraction (TRF) from palm oil (PO) and rice bran
      oil (RBO) has been shown to lower the blood glucose level in patients and
      preclinical animal models. This study was designed to investigate if TRF from PO
      and RBO could improve the renal function in DN by the virtue of their
      hypoglycemic and antioxidant activities. Male Wistar rats having an average body
      weight (bw) 250g were divided into four groups of six each .The first group
      served as diabetic control [injected with 55mg/kg bw of streptozotocin (STZ),
      intraperitoneally], while the second and third group received PO-TRF and RBO-TRF,
      respectively, by gavage at a dose of 200mg/kg bw/day, over a period of 8 weeks
      post-induction of diabetes. The fourth group comprised of age-matched male Wistar
      rats that received single intraperitoneal injection of normal saline only and
      served as control. After 8 weeks of STZ injection and TRF treatment, 24h urine
      was collected and animals were sacrificed. Fasting blood glucose, glycosylated
      hemoglobin, biochemical markers of renal function and oxidative stress were
      evaluated in serum, urine and kidney tissue. The results show that treatment with
      PO-TRF as well as RBO-TRF significantly improved the glycemic status and renal
      function in type 1 diabetic rats but PO-TRF afforded greater efficiency at
      similar dose as compared to RBO-TRF. In conclusion, PO-TRF was found to be more
      effective hypoglycemic and nephroprotective agent in DN than RBO-TRF.

PMID- 20816777
TI  - Carnosic acid: a potent chemopreventive agent against oral carcinogenesis.
AB  - The present study was aimed to investigate the chemopreventive potential of
      carnosic acid in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal
      pouch carcinogenesis. The chemopreventive potential was assessed by analyzing the
      tumor incidence, tumor volume and burden as well as by measuring the status of
      lipid peroxidation, non-enzymatic and enzymatic antioxidants and phase I and
      phase II detoxification enzymes. Oral squamous cell carcinoma was developed in
      the buccal pouch of golden Syrian hamsters by painting with 0.5% DMBA in liquid
      paraffin three times a week for 14 weeks. In the present study, 100% tumor
      formation was observed in hamsters treated with DMBA alone. Also, the status of
      lipid peroxidation, antioxidants and phase I and phase II detoxification enzymes
      were significantly altered during DMBA-induced oral carcinogenesis. Oral
      administration of carnosic acid at a dose of 10mg/kg body weight/day to DMBA
      treated animals completely prevented the tumor formation in the hamsters' buccal
      pouches. Also, carnosic acid exerted potent anti-lipid peroxidative function and
      stimulated the detoxification cascade during DMBA-induced hamster buccal pouch
      carcinogenesis. The results of the present study suggest that the chemopreventive
      potential of carnosic acid is probably due to its anti-lipid peroxidative
      potential and modulating effect on carcinogen detoxification enzymes during DMBA
      induced oral carcinogenesis.

PMID- 20816778
TI  - Anti-inflammatory effects of dietary phenolic compounds in an in vitro model of
      inflamed human intestinal epithelium.
AB  - Phenolic compounds (PCs) are considered to possess anti-inflammatory properties
      and therefore were proposed as an alternative natural approach to prevent or
      treat chronic inflammatory diseases. However their effects are not fully
      understood, particularly at the intestinal level. To further understand their
      mode of action at the molecular level during intestinal inflammation, an in vitro
      model of inflamed human intestinal epithelium was established. Different
      representative dietary PCs, i.e. resveratrol, ellagic and ferulic acids,
      curcumin, quercetin, chrysin, (-)-epigallocatechin-3-gallate (EGCG) and
      genistein, were selected. To mimic intestinal inflammation, differentiated Caco-2
      cells cultivated in bicameral inserts, in a serum-free medium, were treated with
      a cocktail of pro-inflammatory substances: interleukin (IL)-1beta, tumor necrosis
      factor-alpha, interferon-gamma and lipopolysaccharides. The inflammatory state
      was characterized by a leaky epithelial barrier (attenuation of the
      transepithelial electrical resistance) and by an over-expression at the mRNA and
      protein levels for pro-inflammatory markers, i.e. IL-6, IL-8 and monocyte
      chemoattractant protein-1 (MCP-1), quantified by ELISA and by gene expression
      analysis using a low-density array allowing the evaluation of expression level
      for 46 genes relevant of the intestinal inflammation and functional metabolism.
      Treatment with PCs, used at a realistic intestinal concentration, did not affect
      cell permeability. In inflamed cells, the incubation with genistein reduced the
      IL-6 and MCP-1 overproduction, to ca. 50% of the control, whereas EGCG provoked a
      decrease in the IL-6 and IL-8 over-secretion, by 50 and 60%, respectively. This
      occurred for both flavonoids without any concomitant inhibition of the
      corresponding mRNA expression. All the PCs generated a specific gene expression
      profile, with genistein the most efficient in the downregulation of the
      expression, or over-expression, of inflammatory genes notably those linked to the
      arachidonic metabolism pathway. In conclusion, this study provides evidence that
      genistein and EGCG downregulate the inflammatory response in inflamed intestinal
      epithelial cells by a pathway implicating largely a post-transcriptional
      regulatory mechanism.

PMID- 20816779
TI  - Casearin X exhibits cytotoxic effects in leukemia cells triggered by apoptosis.
AB  - Clerodane diterpenes have demonstrated cytotoxic, antiplasmodial and anti-ulcer
      properties. In the present work, we determined the cytotoxic effect of casearin L
      (Cas L), O (Cas O) and X (Cas X) and (-)-hardwickiic acid isolated from Casearia
      sylvestris leaves, and investigated the underlying mechanisms involved in in
      vitro cell death induced by Cas X in HL-60 leukemia cells (0.7, 1.5 and 3.0MUM).
      Cytotoxicity tests demonstrated that Cas X was the most active compound studied,
      showing greater cytotoxic effects against CEM and HL-60 lines (IC(50) of 0.4MUM)
      and human peripheral blood mononuclear cells (PBMC, IC(50) of 1.2MUM). After 24h
      exposure, Cas X caused a decrease in 5-bromo-20-deoxyuridine (BrdU) incorporation
      (36.6 and 24.5% labeling at 0.7 and 1.5MUM, respectively), reduction in
      viability, and increase in apoptotic and necrotic leukemia cells in a dose
      dependent manner evidenced by the trypan blue and AO/EB (acridine orange/ethidium
      bromide) assays. Moreover, Cas X-treated cells exhibited nuclear fragmentation
      and cytoplasmic vacuolization depending on the concentration tested. These
      characteristics of apoptosis or secondary necrosis were confirmed by flow
      cytometry which revealed DNA fragmentation, phosphatidylserine externalization,
      activation of the effector caspases 3/7 and mitochondrial depolarization. We then
      found evidence that Cas X causes cell death via apoptotic pathways, corroborating
      the potential of casearins as compounds with promising antitumor-related
      properties.

PMID- 20816781
TI  - alpha-synuclein aggregation reduces nigral myocyte enhancer factor-2D in
      idiopathic and experimental Parkinson's disease.
AB  - alpha-Synuclein is an abundant neuronal protein that has been linked to both
      normal synaptic function and neurodegenerative disease, in particular,
      Parkinson's disease (PD). Evidence from both in vitro and in vivo studies
      indicate that increased wild type or mutant alpha-synuclein can cause PD, but the
      molecular mechanisms that underlie alpha-synuclein-mediated neurotoxicity remain
      poorly understood. We reported here that myocyte enhancer factor 2D (MEF2D), a
      nuclear transcription factor known to promote neuronal survival, is down
      regulated in response alpha-synuclein accumulation and aggregation. Our data
      demonstrated that levels of cytoplasmic and nuclear MEF2D were significantly
      decreased in PD nigral neurons when compared to the nigra of age-matched controls
      and Alzheimer's disease (AD) cases. This decrease was significantly greater in
      the nigral neurons with alpha-synuclein inclusions. Viral vector-mediated
      overexpression of human alpha-synuclein in rats resulted in significantly
      decreased MEF2D in nigral neurons similar to what was seen in PD. The decline of
      MEF2D-immunoreactivity was associated with a reduction in TH-immunoreactivity.
      These results indicate that the neuronal survival factor MEF2D is decreased in
      human and experimental PD, and this decrease is specifically associated with
      alpha-synuclein accumulation and aggregation.

PMID- 20816782
TI  - 17-AAG increases autophagic removal of mutant androgen receptor in spinal and
      bulbar muscular atrophy.
AB  - Several types of motorneuron diseases are linked to neurotoxic mutant proteins.
      These acquire aberrant conformations (misfolding) that trigger deleterious
      downstream events responsible for neuronal dysfunction and degeneration. The
      pharmacological removal of misfolded proteins might thus be useful in these
      diseases. We utilized a peculiar motorneuronal disease model, spinobulbar
      muscular atrophy (SBMA), in which the neurotoxicity of the protein involved, the
      mutant androgen receptor (ARpolyQ), can be modulated by its ligand testosterone
      (T). 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) has already been proven to
      exert beneficial action in SBMA. Here we demonstrated that 17-AAG exerts its pro
      degradative activity on mutant ARpolyQ without impacting on proteasome functions.
      17-AAG removes ARpolyQ misfolded species and aggregates by activating the
      autophagic system. We next analyzed the 17-AAG effects on two proteins (SOD1 and
      TDP-43) involved in related motorneuronal diseases, such as amyotrophic lateral
      sclerosis (ALS). In these models 17-AAG was unable to counteract protein
      aggregation.

PMID- 20816783
TI  - Changes in hippocampal GABAA/cBZR density during limbic epileptogenesis:
      relationship to cell loss and mossy fibre sprouting.
AB  - Reduced GABA(A)/central benzodiazepine receptor (GABA(A)/cBZR) density, mossy
      fibre sprouting (MFS) and hippocampal cell loss are well described pathological
      features of human temporal lobe epilepsy (TLE), and animal models thereof.
      However, the temporal relationship of their development, and their roles in the
      emergence of the epilepsy, are uncertain. This was investigated in the kainic
      acid (KA)-induced post-status epilepticus (SE) model of TLE. Male Wistar rats (7
      weeks, n=53) were randomised into control and KA groups. At 24h, 2, 4 or 6 weeks
      sham and KA post-SE animals were euthanised, brains extracted and GABA(A)/cBZR
      density, neuronal loss and MFS measured in hippocampal sub-regions. GABA(A)/cBZR
      density (B(max)) was measured by saturation-binding analysis using [(3)H]
      flumazenil. At 24h post-SE GABA(A)/cBZR density was increased in almost all
      hippocampal subregions, but was decreased at the later time points with the
      exception of the dentate gyrus. There was significant neuronal loss in the CA3
      SPc region (-24 +/- 9.3%, p<0.05) at 24h, which remained stable at the later time
      points associated with an elevated GABA(A)/cBZR density per surviving neuron at
      24h post-SE (+56.4%; p<0.05) which returned to control levels by 6 weeks post-SE.
      MFS in the dentate gyrus progressively increased over the 6 weeks following SE
      (+70.6% at 6 weeks), at which time there was a significant inverse relationship
      with GABA(A)/cBZR binding (r(2)=0.87; p=0.02). The temporal evolution of
      GABA(A)/cBZR density changes post-KA-induced SE, and the relationship with
      decreases in hippocampal pyramidal cell numbers and MFS, may point to a key role
      for these changes in the pathogenesis of acquired limbic epileptogenesis.

PMID- 20816784
TI  - Valproic acid induces microglial dysfunction, not apoptosis, in human glial
      cultures.
AB  - Valproic acid (VPA) is widely used for the treatment of mood disorders and
      epilepsy, but its mechanism of action is unclear. In vivo and in vitro studies
      using rodent models have demonstrated that VPA has both neuroprotective and
      neurotrophic effects. These beneficial effects are, in part, through modulation
      of glial cell function. Recently, we and others have shown that VPA selectively
      induces caspase-3 mediated apoptosis in rodent microglial cells. However, the
      effect of VPA on human microglia has not been tested. In this study, using
      microglia derived from adult human brains, we demonstrate that VPA does not
      induce microglial apoptosis as determined by the absence of caspase-3 cleavage.
      However, VPA does partially decrease the expression of the microglial markers
      PU.1 and CD45, as well as dramatically reducing microglial phagocytosis. Due to
      the many roles of microglia in the brain, these VPA-induced alterations in
      microglial phenotype could potentially have major effects on physiological and
      pathological actions of these cells.

PMID- 20816786
TI  - A novel method of detecting mitochondrial m.1494C>T and m.1555A>G mutations in a
      single PCR reaction using base-quenched probe.

PMID- 20816785
TI  - L-type voltage-gated calcium channel blockade with isradipine as a therapeutic
      strategy for Alzheimer's disease.
AB  - There is strong evidence that intracellular calcium dysregulation plays an
      important pathological role in Alzheimer's disease, and specifically that beta
      amyloid may induce increases in intracellular calcium and lead to neuronal cell
      dysfunction and death. Here we investigated the feasibility of modifying
      Alzheimer's pathology with the L-type voltage-gated calcium channel blockers
      verapamil, diltiazem, isradipine and nimodipine. All four compounds protected
      MC65 neuroblastoma cells from amyloid beta protein precursor C-terminal fragment
      (APP CTF)-induced neurotoxicity. Isradipine was the most potent blocker,
      preventing APP CTF neurotoxicity at nanomolar concentrations. Intracellular beta
      amyloid expression was associated with increased expression of Cav 1.2 calcium
      channels and increased intracellular calcium influx from the extracellular space.
      Despite the cytoprotection afforded by calcium channel blockers, amyloid beta
      oligomer formation was not suppressed. The mechanism of cell death in MC65 cells
      is appeared to be caspase-3 independent. With the goal of determining if there is
      sufficient experimental support to move forward with animal trials of isradipine,
      we determined its bioavailability in the triple transgenic mouse model of AD.
      Subcutaneous implantation of carrier-bound isradipine (3 MUg/g/day) for 60 days
      resulted in nanomolar concentrations in both the plasma and brain. Taken
      together, our in vitro results support the theory that calcium blockers exert
      protective effects downstream of the effects of beta amyloid. Isradipine's
      neuroprotective effect at concentrations that are clinically relevant and
      achievable in vitro and in vivo suggests that this particular calcium blocking
      agent may have therapeutic value in the treatment of Alzheimer's disease.

PMID- 20816787
TI  - Total serum cholesterol determination can provide understanding of parasite
      burden in patients with visceral leishmaniasis infection.

PMID- 20816788
TI  - Dysregulation of T(H) type cytokines in the patients of Parthenium induced
      contact dermatitis.
AB  - BACKGROUND: Parthenium contact dermatitis is a major health problem caused by a
      cosmopolitan weed Parthenium hysterophorus. It is a T cell-mediated immune injury
      and disease manifests as itchy erythematous papules, papulovesicular and plaque
      lesions on exposed areas of the body. We studied the involvement of
      T(H)1/T(H)2/T(H)17/Treg type responses by assaying various cytokines in
      Parthenium dermatitis. METHODS: The study includes 50 patients of Parthenium
      dermatitis confirmed by patch testing and 50 healthy subjects. The serum levels
      of T(H)1, T(H)2, T(H)17 and Treg cytokines were estimated by high sensitivity
      sandwich ELISA and were compared statistically between groups using ANOVA.
      RESULTS: The mean concentration of T(H)1 cytokines (p<0.001) and IL-17 (p<0.001)
      were increased significantly as compared to controls. In contrast, decrease in
      levels of IL-10 (p<0.002) and TGF-beta (p<0.001) were significant and levels of
      IL-4 (p<0.262) were insignificant whereas no alterations in the total IgE
      concentrations (p<0.976) was observed. CONCLUSION: The induction of T(H)1 and
      T(H)17 cytokines reinforce the need of detailed analysis of immune dysregulation
      in Parthenium dermatitis and might add some insight in the pathogenesis,
      diagnosis and current treatment modalities of this disease.

PMID- 20816789
TI  - CLL-like monoclonal B-cell lymphocytosis: are we all bound to have it?
AB  - CLL-like monoclonal B-cell lymphocytosis (MBL) shares a unique immunophenotype
      with chronic lymphocytic leukemia (CLL), and represents the vast majority of
      clonal B-cell expansions found in the peripheral blood of otherwise healthy
      subjects. Along with the improvement of laboratory techniques and the widespread
      availability of multiparameter flow cytometry, the finding of tiny aberrant B
      cell populations became more frequent, prompting the need for clinical and
      biological definition of the nature of this condition and its relationship with
      leukemia development. MBL seems to be a melting-pot containing several entities,
      identical in terms of phenotype but with extremely different risks of leukemia
      development (from low to none) that seem to correlate with the number of B
      lymphocytes. CLL-like MBL observed in the clinical setting ("Clinical MBL"),
      usually being characterized by lymphocytosis, demonstrated a sizeable, even if
      low (1.1-1.4% per year), risk of leukemic progression, but represents a minority
      of all MBL cases. The vast majority of CLL-like MBL are detected in general
      population screenings and do not likely have a risk of CLL that is substantially
      higher than that of unaffected individuals. Interestingly, MBL frequency
      increases with age, being virtually undetectable under 40 years of age but being
      present in 50-75% of the people older than 90 years. It has been proposed that
      MBL could be interpreted as an epiphenomenon of a chronic and persistent
      antigenic stimulation. The (rare) possibility to evolve into a frank leukemia
      might then depend on biological and molecular factors insofar unknown that may
      modify the modality of cell reaction as well as the potential to acquire further
      genetic abnormalities. Therefore, the real challenge of the next years in the MBL
      research field is not to increase the sensitivity of detection, neither to
      implement screening protocols to be applied to the general population, rather to
      unravel the biologic features that, at individual level, will identify those
      (few) cases that are at risk of developing a progressive disease.

PMID- 20816790
TI  - The role of the B-cell receptor in the pathogenesis of chronic lymphocytic
      leukaemia.
AB  - The key molecule for normal B cells is the surface Ig (sIg) of the B-cell
      receptor, which influences cell behaviour, even after neoplastic transformation.
      During B-cell maturation, sIg accumulates somatic mutations in the Ig variable
      region (V) genes and tumours retain these patterns, thereby revealing the point
      of differentiation of the B cell of origin. The importance of origin is
      strikingly illustrated in CLL where the two major subsets with distinctive
      clinical behaviour express either unmutated (U) or mutated (M) V genes. Biased
      selection of VDJ genes also occurs in CLL, allowing further identification of the
      normal B-cell counterparts, with U-CLL apparently derived from circulating naive
      B cells. Surface IgM of CLL is functional, with evidence for ongoing interaction
      with antigen in vivo. Signalling connects to cell survival, proliferation and
      migration, key determinants of tumour cell behaviour. Probing of B-cell receptor
      mediated signalling pathways, either constitutively activated or open for
      activation, reveals dynamic, possibly repetitive, stimulatory events, likely to
      occur in tissue sites. Subtle differences in signal responsiveness between U-CLL
      or M-CLL subsets, together with microenvironmental factors, may explain clinical
      outcome. Knowledge of the critical signalling pathways should reveal the steps
      vulnerable to inhibition and allow development of a new range of therapeutic
      drugs, targeted particularly against the more aggressive subset, U-CLL.

PMID- 20816792
TI  - A bicistronic lentiviral vector-based method for differential transsynaptic
      tracing of neural circuits.
AB  - We developed a bicistronic HIV1-derived lentiviral vector system co-expressing
      green fluorescent protein (AcGFP1) and wheat germ agglutinin (WGA) mediated by
      picornaviral 2A peptide. This system was first applied to the analysis of the rat
      cerebellar efferent pathways. When the lentiviral vector was injected into a
      specific lobule, the local Purkinje cell population (first-order neurons) was
      efficiently infected and co-expressed both AcGFP1 and WGA protein. In the second
      order neurons in the cerebellar and vestibular nuclei, WGA but not AcGFP1 protein
      was differentially detected, demonstrating that the presence of AcGFP1 protein
      enables discrimination of first-order neurons from second-order neurons.
      Furthermore, WGA protein was detected in the contralateral ventrolateral thalamic
      nucleus (third-order nucleus). This system also successfully labeled rat cortical
      pathways from the primary somatosensory cortex and monkey cerebellar efferent
      pathways. Thus, this bicistronic lentiviral vector system is a useful tool for
      differential transsynaptic tracing of neural pathways originating from local
      brain regions.

PMID- 20816793
TI  - The effect of HSP-causing mutations in SPG3A and NIPA1 on the assembly,
      trafficking, and interaction between atlastin-1 and NIPA1.
AB  - Despite its genetic heterogeneity, hereditary spastic paraplegia (HSP) is
      characterized by similar clinical phenotypes, suggesting that a common
      biochemical pathway underlies its pathogenesis. In support of this hypothesis, we
      used a combination of immunoprecipitation, confocal microscopy, and flow
      cytometry to demonstrate that two HSP-associated proteins, atlastin-1 and NIPA1,
      are direct binding partners, and interestingly, that the endogenous expression
      and trafficking of these proteins is highly dependent upon their coexpression. In
      addition, we demonstrated that the cellular distribution of atlastin-1:NIPA1
      complexes was dramatically altered by HSP-causing mutations, as missense
      mutations in atlastin-1 (R239C and R495W) and NIPA1 (T45R and G106R) caused
      protein sequestration in the Golgi complex (GC) and endoplasmic reticulum (ER),
      respectively. Moreover, we demonstrated that HSP-causing mutations in both
      atlastin-1 and NIPA1 reduced axonal and dendritic sprouting in cultured rat
      cortical neurons. Together, these findings support the hypothesis that NIPA1 and
      atlastin-1 are members of a common biochemical pathway that supports axonal
      maintenance, which may explain in part the characteristic degeneration of long
      spinal pathways observed in patients with HSP.

PMID- 20816794
TI  - Otx2 and Otx1 protect diencephalon and mesencephalon from caudalization into
      metencephalon during early brain regionalization.
AB  - Otx2 is expressed in each step and site of head development. To dissect each Otx2
      function we have identified a series of Otx2 enhancers. The Otx2 expression in
      the anterior neuroectoderm is regulated by the AN enhancer and the subsequent
      expression in forebrain and midbrain later than E8.5 by FM1 and FM2 enhancers;
      the Otx1 expression takes place at E8.0. In telencephalon later than E9.5 Otx1
      continues to be expressed in the entire pallium, while the Otx2 expression is
      confined to the most medial pallium. To determine the Otx functions in forebrain
      and midbrain development we have generated mouse mutants that lack both FM1 and
      FM2 enhancers (DKO: Otx2(DeltaFM1DeltaFM2/DeltaFM1DeltaFM2)) and examined the TKO
      (Otx1(-/-)Otx2(DeltaFM1DeltaFM2/DeltaFM1DeltaFM2)) phenotype. The mutants develop
      normally until E8.0, but subsequently by E9.5 the diencephalon, including
      thalamic eminence and prethalamus, and the mesencephalon are caudalized into
      metencephalon consisting of isthmus and rhombomere 1; the caudalization does not
      extend to rhombomere 2 and more caudal rhombomeres. In rostral forebrain,
      neopallium, ganglionic eminences and hypothalamus in front of prethalamus
      develop; we propose that they become insensitive to the caudalization with the
      switch from the Otx2 expression under the AN enhancer to that under FM1 and FM2
      enhancers. In contrast, the medial pallium requires Otx1 and Otx2 for its
      development later than E9.5, and the Otx2 expression in diencepalon and
      mesencephalon later than E9.5 is also directed by an enhancer other than FM1 and
      FM2 enhancers.

PMID- 20816795
TI  - Increased expression of FoxM1 transcription factor in respiratory epithelium
      inhibits lung sacculation and causes Clara cell hyperplasia.
AB  - Foxm1 is a member of the Forkhead Box (Fox) family of transcription factors.
      Foxm1 (previously called Foxm1b, HFH-11B, Trident, Win, or MPP2) is expressed in
      multiple cell types and plays important roles in cellular proliferation,
      differentiation and tumorigenesis. Genetic deletion of Foxm1 from mouse
      respiratory epithelium during initial stages of lung development inhibits lung
      maturation and causes respiratory failure after birth. However, the role of Foxm1
      during postnatal lung morphogenesis remains unknown. In the present study, Foxm1
      expression was detected in epithelial cells of conducting and peripheral airways
      and changing dynamically with lung maturation. To discern the biological role of
      Foxm1 in the prenatal and postnatal lung, a novel transgenic mouse line that
      expresses a constitutively active form of FoxM1 (FoxM1 N-terminal deletion mutant
      or FoxM1-DeltaN) under the control of lung epithelial-specific SPC promoter was
      produced. Expression of the FoxM1-DeltaN transgene during embryogenesis caused
      epithelial hyperplasia, inhibited lung sacculation and expression of the type II
      epithelial marker, pro-SPC. Expression of FoxM1-DeltaN mutant during the
      postnatal period did not influence alveologenesis but caused focal airway
      hyperplasia and increased proliferation of Clara cells. Likewise, expression of
      FoxM1-DeltaN mutant in conducting airways with Scgb1a1 promoter was sufficient to
      induce Clara cell hyperplasia. Furthermore, FoxM1-DeltaN cooperated with
      activated K-Ras to induce lung tumor growth in vivo. Increased activity of Foxm1
      altered lung sacculation, induced proliferation in the respiratory epithelium and
      accelerated lung tumor growth, indicating that precise regulation of Foxm1 is
      critical for normal lung morphogenesis and development of lung cancer.

PMID- 20816796
TI  - Deletion of Akt1 causes heart defects and abnormal cardiomyocyte proliferation.
AB  - The PI3K-PDK1-PKB/Akt (PI3K, phosphoinositide-3 kinase; PDK1, phosphoinositide
      dependent protein kinase 1; PKB, protein kinase B) signaling pathway plays a
      critical role in a variety of biological processes including cell survival,
      growth and proliferation, metabolism and organogenesis. Previously, we generated
      Akt1-deficient mice and found high neonatal mortality with unknown causes. Here
      we report that histological analysis of Akt1-deficient embryos and newborns
      revealed heart defects and decreased cell proliferation. Echocardiographic study
      of Akt1-deficient mice indicated decreased heart function. Further investigation
      revealed that Akt1 deficiency caused substantial activation of p38MAPK in the
      heart. Breeding the Akt1-deficient mice to mice that were heterozygous for a null
      p38alpha partially rescued the heart defects, significantly decreased post-natal
      mortality, and restored normal patterns of cardiomyocyte proliferation. Our study
      suggests that Akt1 is essential for heart development and function, in part,
      through suppression of p38MAPK activation.

PMID- 20816797
TI  - VEGF signaling has distinct spatiotemporal roles during heart valve development.
AB  - Heart valve malformations are one of the most common types of birth defects,
      illustrating the complex nature of valve development. Vascular endothelial growth
      factor (VEGF) signaling is one pathway implicated in valve formation, however its
      specific spatial and temporal roles remain poorly defined. To decipher these
      contributions, we use two inducible dominant negative approaches in mice to
      disrupt VEGF signaling at different stages of embryogenesis. At an early step in
      valve development, VEGF signals are required for the full transformation of
      endocardial cells to mesenchymal cells (EMT) at the outflow tract (OFT) but not
      atrioventricular canal (AVC) endocardial cushions. This role likely involves
      signaling mediated by VEGF receptor 1 (VEGFR1), which is highly expressed in
      early cushion endocardium before becoming downregulated after EMT. In contrast,
      VEGFR2 does not exhibit robust cushion endocardium expression until after EMT is
      complete. At this point, VEGF signaling acts through VEGFR2 to direct the
      morphogenesis of the AVC cushions into mature, elongated valve leaflets. This
      latter role of VEGF requires the VEGF-modulating microRNA, miR-126. Thus, VEGF
      roles in the developing valves are dynamic, transitioning from a differentiation
      role directed by VEGFR1 in the OFT to a morphogenetic role through VEGFR2
      primarily in the AVC-derived valves.

PMID- 20816799
TI  - Cdx mutant axial progenitor cells are rescued by grafting to a wild type
      environment.
AB  - Cdx transcription factors are required for axial extension. Cdx genes are
      expressed in the posterior growth zone, a region that supplies new cells for
      axial elongation. Cdx2(+/-)Cdx4(-/-) (Cdx2/4) mutant embryos show abnormalities
      in axis elongation from E8.5, culminating in axial truncation at E10.5. These
      data raised the possibility that the long-term axial progenitors of Cdx mutants
      are intrinsically impaired in their ability to contribute to posterior growth. We
      investigated whether we could identify cell-autonomous defects of the axial
      progenitor cells by grafting mutant cells into a wild type growth zone
      environment. We compared the contribution of GFP labeled mutant and wild type
      progenitors grafted to unlabeled wild type recipients subsequently cultured over
      the period during which Cdx2/4 defects emerge. Descendants of grafted cells were
      scored for their contribution to differentiated tissues in the elongating axis
      and to the posterior growth zone. No difference between the contribution of
      descendants from wild type and mutant grafted progenitors was detected,
      indicating that rescue of the Cdx mutant progenitors by the wild type recipient
      growth zone is provided non-cell autonomously. Recently, we showed that premature
      axial termination of Cdx mutants can be partly rescued by stimulating canonical
      Wnt signaling in the posterior growth zone. Taken together with the data shown
      here, this suggests that Cdx genes function to maintain a signaling-dependent
      niche for the posterior axial progenitors.

PMID- 20816798
TI  - Regeneration and transdetermination: the role of wingless and its regulation.
AB  - Imaginal discs of Drosophila have the remarkable ability to regenerate. After
      fragmentation wound healing occurs, ectopic wg is induced and a blastema is
      formed. In some, but not all fragments, the blastema will replace missing
      structures and a few cells can become more plastic and transdetermine to
      structures of other discs. A series of systematic cuts through the first leg disc
      revealed that a cut must transect the dorsal-proximal disc area and that the
      fragment must also include wg-competent cells. Fragments that fail to both
      transdetermine and regenerate missing structures will do both when provided with
      exogenous Wg, demonstrating the necessity of Wg in regenerative processes. In
      intact leg discs ubiquitously expressed low levels of Wg also leads to blastema
      formation, regeneration and transdetermination. Two days after exogenous wg
      induction the endogenous gene is activated, leading to elevated levels of Wg in
      the dorsal aspect of the leg disc. We identified a wg enhancer that regulates
      ectopic wg expression. Deletion of this enhancer increases transdetermination,
      but lowers the amount of ectopic Wg. We speculate that this lessens repression of
      dpp dorsally, and thus creates a permissive condition under which the balance of
      ectopic Wg and Dpp is favorable for transdetermination.

PMID- 20816800
TI  - Protein kinase A regulates GDNF/RET-dependent but not GDNF/Ret-independent
      ureteric bud outgrowth from the Wolffian duct.
AB  - Embryonic kidney development begins with the outgrowth of the ureteric bud (UB)
      from the Wolffian duct (WD) into the adjacent metanephric mesenchyme (MM). Both a
      GDNF-dependent and GDNF-independent (Maeshima et al., 2007) pathway have been
      identified. In vivo and in vitro, the GDNF-dependent pathway is inhibited by
      BMPs, one of the factors invoked to explain the limitation of UB formation in the
      unbudded regions of the WD surrounding the UB. However, the exact mechanism
      remains unknown. Here a previously described in vitro system that models UB
      budding from the WD was utilized to study this process. Because Protein kinase A
      (PKA) activation has been shown to prevent migration, morphogenesis and
      tubulogenesis of epithelial cells (Santos et al., 1993), its activity in budded
      and non-budded portions of the GDNF-induced WD was analyzed. The level of PKA
      activity was 15-fold higher in the unbudded portions of the WD compared to budded
      portions, suggesting that PKA activity plays a key role in controlling the site
      of UB emergence. Using well-characterized PKA agonists and antagonists, we
      demonstrated that at various levels of the PKA-signaling hierarchy, PKA regulates
      UB outgrowth from the WD by suppressing budding events. This process appeared to
      be PKA-2 isoform specific, and mediated by changes in the duct rather than the
      surrounding mesenchyme. In addition, it was not due to changes in either the
      sorting of junctional proteins, cell death, or cell proliferation. Furthermore,
      the suppressive effect of cAMP on budding did not appear to be mediated by spread
      to adjacent cells via gap junctions. Conversely, antagonism of PKA activity
      stimulated UB outgrowth from the WD and resulted in both an increase in the
      number of buds per unit length of WD as well as a larger surface area per bud.
      Using microarrays, analysis of gene expression in GDNF-treated WDs in which the
      PKA pathway had been activated revealed a nearly 14-fold decrease in Ret, a
      receptor for GDNF. A smaller decrease in GFRalpha1. a co-receptor for GDNF, was
      also observed. Using Ret-null WDs, we were able to demonstrate that PKA regulated
      GDNF-dependent budding but not GDNF-independent pathway for WD budding. We also
      found that BMP2 was higher in unbudded regions of the GDNF-stimulated WD.
      Treatment of isolated WDs with BMP2 suppressed budding and resulted in a 3-fold
      increase in PKA activity. The data suggests that the suppression of budding by
      BMPs and possibly other factors in non-budded zones of the WD may be regulated in
      part by increased PKA activity, probably partially through downregulation of
      Ret/GFRalpha1 coreceptor expression.

PMID- 20816801
TI  - Tbx1 regulates progenitor cell proliferation in the dental epithelium by
      modulating Pitx2 activation of p21.
AB  - Tbx1(-/-) mice present with phenotypic effects observed in DiGeorge syndrome
      patients however, the molecular mechanisms of Tbx1 regulating craniofacial and
      tooth development are unclear. Analyses of the Tbx1 null mice reveal incisor
      microdontia, small cervical loops and BrdU labeling reveals a defect in
      epithelial cell proliferation. Furthermore, Tbx1 null mice molars are lacking
      normal cusp morphology. Interestingly, p21 (associated with cell cycle arrest) is
      up regulated in the dental epithelium of Tbx1(-/-) embryos. These data suggest
      that Tbx1 inhibits p21 expression to allow for cell proliferation in the dental
      epithelial cervical loop, however Tbx1 does not directly regulate p21 expression.
      A new molecular mechanism has been identified where Tbx1 inhibits Pitx2
      transcriptional activity and decreases the expression of Pitx2 target genes, p21,
      Lef-1 and Pitx2c. p21 protein is increased in PITX2C transgenic mouse embryo
      fibroblasts (MEF) and chromatin immunoprecipitation assays demonstrate endogenous
      Pitx2 binding to the p21 promoter. Tbx1 attenuates PITX2 activation of endogenous
      p21 expression and Tbx1 null MEFs reveal increased Pitx2a and activation of
      Pitx2c isoform expression. Tbx1 physically interacts with the PITX2 C-terminus
      and represses PITX2 transcriptional activation of the p21, LEF-1, and Pitx2c
      promoters. Tbx1(-/+)/Pitx2(-/+) double heterozygous mice present with an extra
      premolar-like tooth revealing a genetic interaction between these factors. The
      ability of Tbx1 to repress PITX2 activation of p21 may promote cell
      proliferation. In addition, PITX2 regulation of p21 reveals a new role for PITX2
      in repressing cell proliferation. These data demonstrate new functional
      mechanisms for Tbx1 in tooth morphogenesis and provide a molecular basis for
      craniofacial defects in DiGeorge syndrome patients.

PMID- 20816803
TI  - Functional analysis of two invertebrate-type lysozymes from red swamp crayfish,
      Procambarus clarkii.
AB  - Lysozyme is an important immune effector and is widely distributed in many
      organisms. In the present study, two novel invertebrate-type lysozymes (Pclysi1
      and Pclysi2) were cloned from red swamp crayfish, Procambarus clarkii. Alignment
      analysis showed that these two genes were different in catalytic residues.
      Results of RT-PCR showed that these two genes share similar tissue distribution
      patterns, and both were upregulated after bacteria challenge. The mature
      recombinant proteins were expressed in Escherichia coli system and purified.
      Activity analysis revealed that rPclysi1 had no muramidase activity and
      isopeptidase activity, but had antimicrobial activity. Meanwhile, rPclysi2 was
      muramidase-deficient and had no antimicrobial activity, but possessed
      isopeptidase activity. Above data suggest that Pclysi1 and 2 may offer different
      functions in the crayfish immunity.

PMID- 20816804
TI  - Characterization of an antiserum against Atlantic cod (Gadus morhua L.) g-type
      lysozyme.
AB  - In this study we describe the production and characterization of an antiserum
      against recombinant g-type lysozyme derived from Atlantic cod. This is also the
      first initial analyses of g-type lysozyme protein expression in tissues of
      Atlantic cod. Recombinant expression and purification of cod g-type lysozyme was
      used for immunization to rabbit and the rabbit sera were analysed for anti g-type
      lysozyme antibodies using enzyme-linked immunosorbent assay (ELISA), Western blot
      and immunohistochemistry. ELISA results showed that antibody titres were mounted
      between 12,800 and 25,600 as measured at an optical density corresponding to 50%
      of the maximal level. By Western blot analysis the rabbit immune serum detected a
      single ~23 kDa band representing the size of the injected antigen, in both spleen
      and head kidney homogenates from the Atlantic cod. Immunohistochemisrty detected
      the native folded g-type lysozyme in tissues and revealed that g-type lysozyme
      positive cells were observed in haematopoietic tissue of the head kidney and in
      red pulp of spleen. In conclusion, the rabbit anti g-type lysozyme immune sera
      was developed and is effectively utilized for ELISA, Western analysis as well as
      for immunohistochemistry. This has allowed us to obtain new knowledge about this
      protein regarding localization and distribution in cod tissue.

PMID- 20816805
TI  - Immunoglobulin M gene expression analysis of orange-spotted grouper, Epinephelus
      coioides, following heat shock and Vibrio alginolyticus challenge.
AB  - The present study aimed to examine the expression of immunoglobulin M (IgM) gene
      in orange-spotted grouper (Epinephelus coioides) following thermal stress,
      bacterial infection, and immunization with formalin-killed Vibrio alginolyticus,
      a kind of bacterial pathogen that causes septicemia. In heat shock experiments,
      twenty-five healthy orange-spotted grouper were kept in tanks with seawater at
      37+/-0.5 degrees C for one hour heat-shock treatment, and then returned to 27+/
      0.5 degrees C seawater tanks. In bacterial challenge experiments, two hundred
      healthy orange-spotted grouper were infected or immunized intraperitoneally with
      0.1 mL V. alginolyticus resuspended in PBS at 5*10(4) cells mL(-1). Blood and
      organ samples (head kidney, spleen, and thymus gland) were collected and frozen
      immediately in liquid nitrogen for subsequent real-time PCR analyses at various
      times. IgM mRNA expression decreased significantly in gill, head kidney, spleen,
      intestine, and thymus gland from the 3rd hour after heat stress (37 degrees C),
      and consistently declined until the 48th hour, but increased in blood cells from
      the 3rd hour to 48th hour. There was a significant increase of IgM gene
      transcripts in head kidney, spleen, thymus gland and blood cells of the infected
      and immunized grouper. There was a clear time-dependent expression pattern of IgM
      mRNA expression after V. alginolyticus infection and vaccination, with a
      significant increase at 2 weeks post-challenge and a peak at 4 weeks or 5 weeks
      for the infection or vaccination group, respectively. The level of IgM mRNA
      expression in the infected grouper was not only higher, but also earlier than
      that of the immunized group. These data demonstrated that IgM mRNA expression of
      the grouper was influenced by acute thermal stress and V. alginolyticus
      challenge.

PMID- 20816806
TI  - Dietary administration of the probiotic, Saccharomyces cerevisiae P13, enhanced
      the growth, innate immune responses, and disease resistance of the grouper,
      Epinephelus coioides.
AB  - The percent weight gain (PWG) and feeding efficiency (FE) of Epinephelus coioides
      were calculated. The survival of Saccharomyces cerevisiae P13 in the posterior
      intestines using a specific primer pair of YMR245w-F/YMR245w-R, non-specific
      immune parameters of grouper, and its susceptibility to Streptococcus sp. and an
      iridovirus were determined when the fish were fed diets containing S. cerevisiae
      at 0 (control), 10(3), 10(5), or 10(7) colony-forming units (cfu) kg(-1) for 4
      weeks. Results showed that grouper fed a diet containing S. cerevisiae at the
      levels of 10(3), 10(5), and 10(7) cfu kg(-1) had significantly increased PGW and
      FE especially in the 10(7) cfu kg(-1) group which were 211.6% and 1.2,
      respectively. S. cerevisiae was able to survive in the fish posterior intestines
      during the S. cerevisiae feeding period. Fish fed a diet containing S. cerevisiae
      at 10(7) cfu kg(-1) had significantly higher survival rates than those fed the
      10(3) cfu kg(-1)S. cerevisiae diet and the control diet after challenge with
      Streptococcus sp. and an iridovirus, with increased survival rates of 26.6% and
      36.6%, respectively, compared to the challenge control group. The phagocytic
      activity, respiratory burst and superoxide dismutase (SOD) level of head kidney
      leucocytes as well as serum lysozyme activity and serum alternative complement
      activity (ACH(50)) of fish fed diets containing S. cerevisiae at 10(5) and 10(7)
      cfu kg(-1) were significantly higher than those of fish fed the 10(3) cfu kg(
      1)S. cerevisiae-contained diet and the control diets after 4 weeks of feeding,
      and had increased by 20% and 20%, 27.6% and 19.7%, 30.5% and 36.2%, 205.8% and
      169.6%, and 90.8% and 80.3%, respectively, compared to the control group. We
      therefore recommend dietary S. cerevisiae administration of 10(5) and 10(7) cfu
      kg(-1) to E. coioides to promote growth and enhance immunity and resistance
      against Streptococcus sp. and an iridovirus especially in the 10(7) cfu kg(-1)
      group.

PMID- 20816807
TI  - Deep sequencing of the innate immune transcriptomic response of zebrafish embryos
      to Salmonella infection.
AB  - Salmonella enterica serovar Typhimurium (S. typhimurium) bacteria cause an
      inflammatory and lethal infection in zebrafish embryos. To characterize the
      embryonic innate host response at the transcriptome level, we have extended and
      validated previous microarray data by Illumina next-generation sequencing
      analysis. We obtained 10 million sequence reads from control and Salmonella
      infected zebrafish embryos using a tag-based sequencing method (DGE or Tag-Seq)
      and 15 million reads using whole transcript sequencing (RNA-Seq), which
      respectively mapped to circa 65% and 85% of 28,716 known Ensembl transcripts.
      Both sequencing methods showed a strong correlation of sequence read counts per
      transcript and an overlap of 241 transcripts differentially expressed in response
      to infection. A lower overlap of 165 transcripts was observed with previous
      microarray data. Based on the combined sequencing-based and microarray-based
      transcriptome data we compiled an annotated reference set of infection-responsive
      genes in zebrafish embryos, encoding transcription factors, signal transduction
      proteins, cytokines and chemokines, complement factors, proteins involved in
      apoptosis and proteolysis, proteins with anti-microbial activities, as well as
      many known or novel proteins not previously linked to the immune response.
      Furthermore, by comparison of the deep sequencing data of S. typhimurium
      infection in zebrafish embryos with previous deep sequencing data of
      Mycobacterium marinum infection in adult zebrafish we derived a common set of
      infection-responsive genes. This gene set consists of known and putative innate
      host defense genes that are expressed both in the absence and presence of a fully
      developed adaptive immune system and that provide a valuable reference for future
      studies of host-pathogen interactions using zebrafish infection models.

PMID- 20816808
TI  - Proline-rich domain of penaeidin molecule exhibits autocrine feature by
      attracting penaeidin-positive granulocytes toward the wound-induced inflammatory
      site.
AB  - Antimicrobial peptides (AMPs) are amphipathic structures of low molecular weight
      that are generally positively charged. Penaeidins are shrimp-specific AMPs that
      are synthesized and stored in granulocytes and released after stimulation.
      Penaeidin is composed of an N-terminal proline-rich domain (PRD) and a C-terminal
      cysteine-rich domain (CRD). Penaeidin and PRD were approved as a cytokine in
      vitro, but how penaeidin regulates hemocyte adhesion in vivo is unclear. The
      present study examines penaeidin immunomodulation function in the wound-induced
      inflammation response in tiger shrimp (Penaeus monodon). Both penaeidin
      transcript and protein decreased in peripheral hemocytes but increased in the
      wound tissue. The wounded tissue sections were compared in penaeidin normal and
      penaeidin knockdown shrimps. Only the shrimps at normal penaeidin expression
      level present the concentration of hemocytes phenomenon in the wounded tissue at
      2h post-wound. This phenomenon was recovered in the penaeidin knockdown shrimps
      by adding recombinant penaeidin or PRD to the wounded tissue. Penaeidin was also
      found to be simultaneous expression of integrin in vivo. Penaeidin-positive
      granulocytes decreased in the peripheral hemolymph post-wound. The hemocytes that
      concentrated in the wounded tissue were 80% penaeidin-positive granulocytes. We
      propose that penaeidin acts as a pro-inflammatory cytokine and attracts penaeidin
      positive granulocytes toward the inflammatory site by autocrine activity through
      integrin-dependent cell migration.

PMID- 20816809
TI  - Lactobacillus sakei BK19 enriched diet enhances the immunity status and disease
      resistance to streptococcosis infection in kelp grouper, Epinephelus bruneus.
AB  - The effect of Lactobacillus sakei BK19 (10(8) cells g(-1)) supplemented diet fed
      to kelp grouper, Epinephelus bruneus against streptococcosis caused by
      Streptococcus iniae and Streptococcus parauberis with reference to the innate
      immune response and disease resistance was evaluated at 1, 2, and 4 weeks.
      Maximum reduction in mortalities was observed in kelper feeding the probiotic
      diet for two weeks after challenged with the pathogens when compared to the
      infected group fed with basal diet; similarly the cellular and humoral immune
      responses such as head kidney macrophage phagocytic and peroxidase activities,
      serum lysozyme activity, and total protein levels increased significantly. The
      results reveal that, in streptococcosis infected kelp grouper feeding L. sakei
      BK19 enriched diet affords a higher level of disease protection due to
      stimulation of immune system.

PMID- 20816810
TI  - Activation of phosphatidylinositol 3-kinase/Akt signaling pathway and endogenous
      nitric oxide are needed for the antiarrhythmic effect of centrally administered
      rilmenidine.
AB  - Activation of imidazoline receptors in the central nervous system has protective
      effect on several types of arrhythmias. We demonstrated that centrally
      administered rilmenidine, a selective imidazoline receptor agonist, prevented
      adrenaline-induced arrhythmias during halothane anaesthesia. However, detailed
      myocardial signaling of the antiarrhythmic effect remains to be unexplored. The
      present study was designed to examine a role of pertussis toxin-sensitive G
      protein, phosphatidylinositol 3-kinase/Akt signaling pathway and endogenous
      nitric oxide in the antiarrhythmic effect of rilmenidine. Male Sprague-Dawley
      rats were anaesthetized with halothane and monitored continuously for arterial
      blood pressure and premature ventricular contractions. The arrhythmogenic dose of
      adrenaline was defined as the smallest dose producing 3 or more premature
      ventricular contractions within 15-s period. Firstly, we confirmed that centrally
      administered rilmenidine prevented adrenaline-induced arrhythmias during
      halothane anaesthesia and examined the effect of pertussis toxin, wortmannin (a
      phosphatidylinositol 3-kinase inhibitor), and nitro-L-arginine methyl ester (L
      NAME) (a specific nitric oxide synthesis inhibitors), on the antiarrhythmic
      effect of rilmenidine. We also performed Western blot analysis to determine
      phosphorylation of Akt and glycogen synthase kinase 3beta, a direct Akt
      downstream target, following the central administration of rilmenidine. The
      antiarrhythmic effect of rilmenidine was significantly inhibited by pertussis
      toxin, wortmannin and L-NAME. Rilmenidine increased Akt and glycogen synthase
      kinase 3beta phosphorylation (28+/-13% and 32+/-13%, respectively), and this
      action was abolished by wortmannin. The present results demonstrated that
      pertussis toxin-sensitive G protein, phosphatidylinositol 3-kinase-Akt-GSK3beta
      signaling pathway and endogenous nitric oxide may play a key role in
      antiarrhythmic effect of centrally administered rilmenidine.

PMID- 20816811
TI  - Pachymic acid stimulates glucose uptake through enhanced GLUT4 expression and
      translocation.
AB  - In an effort to investigate the effect and mechanism of Poria cocos on glucose
      uptake, six lanostane-type triterpenoids were isolated and analyzed. Among them,
      pachymic acid displayed the most significant stimulating activity on glucose
      uptake in 3T3-L1 adipocytes. The effect of pachymic acid on the expression
      profile of glucose transporters in differentiated 3T3-L1 adipocytes was also
      analyzed. Our results demonstrated that pachymic acid induced an increase in
      GLUT4, but not GLUT1, expression at both the mRNA and protein levels. The role of
      GLUT4 was further confirmed using the lentiviral vector-derived GLUT4 short
      hairpin RNA (shRNA). The stimulating activity of pachymic acid on glucose uptake
      was abolished when the endogenous GLUT4 expression was suppressed in 3T3-L1
      adipocytes. In addition to increased GLUT4 expression, pachymic acid stimulated
      GLUT4 redistribution from intracellular vesicles to the plasma membrane in
      adipocytes. Exposure of the differentiated adipocytes to pachymic acid increased
      the phosphorylation of insulin receptor substrate (IRS)-1, AKT and AMP-activated
      kinase (AMPK). The involvement of PI3K and AMPK in the action of pachymic acid
      was further confirmed as PI3K and AMPK inhibitors completely blocked the pachymic
      acid-mediated activities in adipocytes. In addition, pachymic acid was shown to
      induce triglyceride accumulation and inhibit lipolysis in differentiated
      adipocytes. Taken together, we demonstrated the insulin-like activities of this
      compound in stimulating glucose uptake, GLUT4 gene expression and translocation,
      and promoting triglyceride accumulation in adipocytes. Our study provides
      important insights into the underlying mechanism of hypoglycemic activity of P.
      cocos.

PMID- 20816812
TI  - Effect of bupivacaine on sevoflurane-induced preconditioning in isolated rat
      hearts.
AB  - Volatile anesthetics protect the heart against ischemia-reperfusion injury. As an
      adjunct to general anesthesia, local and regional application of bupivacaine is
      often used. However, systemic plasma levels of bupivacaine might be
      cardiodepressant and interfere with sevoflurane-induced cardioprotection. Effects
      of bupivacaine on sevoflurane-induced cardioprotection were assessed in isolated
      Langendorff-perfused rat hearts subjected to 35 min of global ischemia followed
      by 60 min reperfusion. Hearts (n=40) were randomized to different groups: 1.
      CONTROL; 2. Bupivacaine: addition of 0.125 or 1.0 MUg/ml bupivacaine to the
      perfusate for 40 min prior to ischemia-reperfusion; 3. Sevoflurane:
      preconditioning induced by three times 5-min episodes of sevoflurane (2.5 vol.%)
      prior to ischemia-reperfusion; 4. Bupivacaine-sevoflurane: combined application
      of bupivacaine and sevoflurane. After ischemia-reperfusion, cardioprotection was
      assessed from infarct size and recovery of ventricular function, and
      phosphorylation levels of glycogen synthase kinase 3beta (GSK3beta) and 5'AMP
      activated protein kinase (AMPK) were determined. Infarct size was reduced in the
      sevoflurane and bupivacaine-sevoflurane groups (Sevo: 23+/-7% and Bupi-Sevo: 23+/
      5% vs. CONTROL: 59+/-6%, P<0.05). In the bupivacaine group infarct size was
      reduced as well (34+/-3%). In the sevoflurane and bupivacaine-sevoflurane groups
      the recovery of left ventricular function (+dP/dt) was improved (Sevo: 59+/-2%
      and Bupi-Sevo: 59+/-2% vs. CONTROL: 47+/-3%, P<0.05), but not in the bupivacaine
      group (48+/-3%). AMPK and GSK3beta phosphorylation were increased by sevoflurane
      but not by bupivacaine. Sevoflurane-induced cardioprotection was not affected by
      bupivacaine in the non-cardiotoxic range. Bupivacaine alone also reduced infarct
      size. Both anesthetics activated different signaling kinases, indicating the
      existence of different cardioprotective intracellular signaling cascades.

PMID- 20816813
TI  - HZ08, a great regulator to reverse multidrug resistance via cycle arrest and
      apoptosis sensitization in MCF-7/ADM.
AB  - In early studies, it was demonstrated that R-HZ08, S-HZ08 and the racemate had
      strong reverse efficacy of multidrug resistance in vitro and in vivo (Yan et al.,
      2008b). The effect was supposed to have direct interaction with multidrug
      resistance-associated protein (MRP1) in MCF-7/ADM and P-glycoprotein in K562/A02.
      According to our latest study, we found HZ08 could enhance chemotherapy induced
      apoptosis by synergistic action on reactive oxygen species generation, GSH
      depletion, mitochondrial membrane potential depolarization, cytochrome c release
      and caspase activation. Moreover, the potential selective effect of HZ08 on
      resistant cells suggested that HZ08 have specific targets for resistance reversal
      via apoptosis regulation. Therefore, we traced individual influence of HZ08, not
      only on apoptosis pathway per se but also on apoptosis related intracellular
      regulation systems. Then we found HZ08 could increase cells in G(0)/G(1) phase
      and regulate apoptosis related proteins (Bcl-2, Bax) as well as upstream
      functional molecules (c-Myc and c-Fos), which are usually abnormal in malignancy
      and responsible for multidrug resistance in MCF-7/ADM. Thereby, chemotherapy
      induced apoptosis was promoted. R-HZ08 showed better effect than S-HZ08 or the
      racemate did in most of targets above. Furthermore, HZ08 did not change the
      concentration of intracellular Ca(2+) which means it would not have side effect
      as verapamil does. Considering multidrug resistance is multifactorial, HZ08,
      especially R-HZ08, which could sensitize apoptosis by multiple improvements of
      upstream malignant characters, will be a promising drug to enhance the effect of
      chemotherapy in the treatment of multidrug resistant tumor.

PMID- 20816814
TI  - Sertraline increases extracellular levels not only of serotonin, but also of
      dopamine in the nucleus accumbens and striatum of rats.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are a first-line treatment for
      depression. Recent reports in the literature describe differences in
      antidepressant effects among SSRIs. Although each SSRI apparently has different
      pharmacological actions aside from serotonin reuptake inhibition, the relations
      between antidepressant effects and unique pharmacological properties in
      respective SSRIs remain unclear. This study was designed to compare abilities of
      three systemically administered SSRIs to increase the extracellular levels of
      serotonin, dopamine, and noradrenaline acutely in three brain regions of male
      Sprague-Dawley rats. We examined effects of sertraline, fluvoxamine, and
      paroxetine on extracellular serotonin, dopamine, and noradrenaline levels in the
      medial prefrontal cortex, nucleus accumbens and striatum of rats using in vivo
      microdialysis. Dialysate samples were collected in sample vials every 20 min for
      460 min. Extracellular serotonin, dopamine, and noradrenaline levels were
      determined using high-performance liquid chromatography with electrochemical
      detection. All SSRI administrations increased extracellular serotonin levels in
      all regions. Only sertraline administration increased extracellular dopamine
      concentrations in the nucleus accumbens and striatum. All SSRI administrations
      increased extracellular noradrenaline levels in the nucleus accumbens, although
      fluvoxamine was less effective. These results suggest that neurochemical
      differences account for the differences in clinical antidepressant effects among
      SSRIs.

PMID- 20816815
TI  - Dopamine D1-like receptors play only a minor role in the increase of striatal
      dopamine induced by striatally applied SKF38393.
AB  - We studied the effects of the intra-striatal infusion of Ca(2+)-free medium on
      the intra-striatal injection of 0.5 MUg SKF38393-induced striatal dopamine
      efflux. It is discussed that the amount of extracellular, striatal dopamine seen
      after striatally applied SKF38393, is the overall result of the (a) release of
      dopamine from the alpha-methyl-para-tyrosine-sensitive and Ca(2+)-insensitive
      pool of newly synthesised dopamine, (b) release of dopamine from the reserpine
      sensitive and Ca(2+)-sensitive storage pool, (c) inhibition of uptake of dopamine
      into nerve terminals and glial cells, and (d) facilitation respectively of the
      inhibition of uptake into blood vessels: dopamine D1-like receptors play only a
      very limited role in these processes. The present study underlines our previous
      notion that the effects of SKF38393 cannot simply be ascribed to the dopamine D1
      like receptor stimulation (Saigusa et al., 2009): in fact, the present study
      clearly reveals that SKF38393 is not at all selective in that respect.

PMID- 20816816
TI  - Importance of M2-M3 loop in governing properties of genistein at the alpha7
      nicotinic acetylcholine receptor inferred from alpha7/5-HT3A chimera.
AB  - Genistein and 5-hydroxyindole (5-HI) potentiate the alpha7 nicotinic
      acetylcholine receptor current by primarily increasing peak amplitude, a property
      of type I alpha7 positive allosteric modulation. In this study, the effects of
      these two compounds were investigated at two different alpha7/5-HT(3) chimeras
      (chimera 1, comprising of extracellular alpha7 N-terminus fused to the remainder
      of 5-HT(3A), and chimera 2 containing an additional alpha7 encoded M2-M3 loop),
      and wild-type alpha7 and 5-HT(3A) receptors. Agonist-evoked responses, examined
      by expression of the chimeras in Xenopus laevis oocytes or HEK-293 cells,
      revealed that currents decayed slower and compounds {rank order: N-[(3R)-1
      azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride (PNU-282987)~2-(1,4
      diazabicyclo[3.2.2]nonan-4-yl)-5-phenyl-1,3,4-oxadiazole
      (NS6784)>acetylcholine>choline} were more potent in chimera 2 than chimera 1 or
      alpha7 receptors. In chimera 2, genistein and 5-HI potentiated agonist-evoked
      responses (EC(50): 4-5 MUM for genistein and 300-500 MUM for 5-HI) and at higher
      concentrations evoked current directly consistent with ago-allosteric modulation.
      At chimera 1 and 5-HT(3A) receptors, neither compound directly evoked any current
      and 5-HI, only at chimera 1, was able to potentiate agonist-evoked responses.
      Genistein and 5-HI did not inhibit the binding of the alpha7 agonist
      [(3)H](1S,4S)-2,2-dimethyl-5-(6-phenylpyridazin-3-yl)-5-aza-2
      azoniabicyclo[2.2.1] heptane ([(3)H]A-585539) to rat brain or chimera 2. In
      summary, this study supports the role of the M2-M3 loop being critical for the
      positive allosteric effect of genistein, but not 5-HI, and in agonist-evoked
      response fine-tuning. The identification of distinct alpha7 receptor modulatory
      sites offers unique opportunities for developing CNS therapeutics and
      understanding its pharmacology.

PMID- 20816819
TI  - Cycling exercise affects the expression of apoptosis-associated microRNAs after
      spinal cord injury in rats.
AB  - There are two major aspects to a spinal cord injury (SCI): an acute, primary
      mechanical trauma and a progressive phase of secondary tissue damage provoked by
      inflammation, excitotoxicity, apoptosis, and demyelination. MicroRNAs (miRs) are
      small, ~22 nucleotide, non-protein-coding RNAs that function at the post
      transcriptional level to regulate gene expression. They have important roles in
      homeostatic processes such as cell proliferation and programmed cell death. In
      the injured rat spinal cord we performed an expression analysis of miRs and their
      downstream targets involved in apoptotic pathways and used post-injury cycling
      exercise to test for activity-dependent plasticity of miR expression. We show
      that SCI results in increased expression of miR Let-7a and miR16 while exercise
      leads to elevated levels of miR21 and decreased levels of miR15b. These changes
      in miR expression are correlated with changes in expression of their target
      genes: pro-apoptotic (decreased PTEN, PDCD4, and RAS mRNA) and anti-apoptotic
      (increased Bcl-2 mRNA) target genes. This is accompanied by a down-regulation of
      mRNA for caspase-7 and caspase-9 and reduced levels of caspase-7 protein. These
      results indicate possible beneficial effects of exercise through action on
      multiple miRs and their targets that contribute to the functional regulation of
      apoptosis after SCI.

PMID- 20816817
TI  - Between a rock and a hard polytomy: rapid radiation in the rupicolous girdled
      lizards (Squamata: Cordylidae).
AB  - Girdled lizards (Cordylidae) are sub-Saharan Africa's only endemic squamate
      family and contain 80 nominal taxa, traditionally divided into four genera:
      Cordylus, Pseudocordylus, Chamaesaura and Platysaurus. Previous phylogenetic
      analysis revealed Chamaesaura and Pseudocordylus to be nested within Cordylus,
      and the former genera were sunk into the later. This taxonomic revision has
      received limited support due to the study's poor taxon sampling, weakly supported
      results and possible temporary nomenclatural instability. Our study analyzes
      three nuclear and three mitochondrial genes from 111 specimens, representing 51
      in-group taxa. Parsimony, likelihood and Bayesian analyses of concatenated and
      partitioned datasets consistently recovered a comb-like tree with 10, well
      supported, monophyletic lineages. Our taxonomic reassessment divides the family
      into 10 genera, corresponding to these well-supported lineages. Short internodes
      and low support between the non-platysaur lineages are consistent with a rapid
      radiation event at the base of the viviparous cordylids.

PMID- 20816818
TI  - Mesenchymal stromal cells fail to prevent acute graft-versus-host disease and
      graft rejection after dog leukocyte antigen-haploidentical bone marrow
      transplantation.
AB  - Mesenchymal stromal cells (MSCs) have been shown to have immunosuppressive
      effects in vitro. To test the hypothesis that these effects can be harnessed to
      prevent graft-versus-host disease (GVHD) and graft rejection after hematopoietic
      cell transplantation (HCT), we administered a combination of 3 different
      immortalized marrow-derived MSC lines (15-30 * 106 MSCs/kg/day, 2-5 times/week)
      or third-party primary MSC (1.0 * 106 MSCs/kg/day, 3 times/week) to canine
      recipients (n = 15) of dog leukocyte antigen-haploidentical marrow grafts
      prepared with 9.2 Gy of total body irradiation. Additional pharmacological
      immunosuppression was not given after HCT. Before their in vivo use, the MSC
      products were shown to suppress alloantigen-induced T cell proliferation in a
      dose-dependent, major histocompatibility complex-unrestricted, and cell contact
      independent fashion in vitro. Among 14 evaluable dogs, 7 (50%) rejected their
      grafts and 7 engrafted, with ensuing rapidly fatal acute GVHD (50%). These
      observations were not statistically different from outcomes obtained with
      historical controls (n = 11) not given MSC infusions (P = .69). Thus, survival
      curves for MSC-treated dogs and controls were virtually superimposable (median
      survival, 18 vs 15 days, respectively). Finally, outcomes of dogs given primary
      MSCs (n = 3) did not appear to be different from those given clonal MSCs (n =
      12). In conclusion, our data fail to demonstrate MSC-mediated protection against
      GVHD and allograft rejection in this model.

PMID- 20816820
TI  - The phrenic motor nucleus in the adult mouse.
AB  - The present study was performed to establish an anatomical context for studies of
      phrenic motor function in mouse models of central nervous system trauma and
      disease. Application of cholera toxin beta-subunit to the diaphragm of adult
      C57BL/6 mice revealed a columnar organization of phrenic motoneurons (PhMNs)
      which extended from rostral C3 to C6. Injection of Miniruby into the
      ventrolateral medulla revealed decussating, anterogradely labeled axons in the
      cervical spinal cord. In addition, application of the transneuronal tracer
      pseudorabies virus (PRV) to the right hemidiaphragm demonstrated a population of
      putative pre-phrenic interneurons at the level of the infected PhMN pool. These
      neuroanatomical features of the mouse phrenic nucleus are consistent with those
      described in other species and provide a foundation for studies of
      neuroplasticity and repair in relation to a functionally and anatomically
      identified spinal network.

PMID- 20816821
TI  - A pyrazole curcumin derivative restores membrane homeostasis disrupted after
      brain trauma.
AB  - We have assessed potential mechanisms associated with the deleterious effects of
      TBI on the integrity of plasma membranes in the hippocampus, together with
      consequences for behavioral function. In addition, we have investigated the
      efficacy of a dietary intervention based on a pyrazole curcumin derivative with
      demonstrated bioactivity and brain absorption, to re-establish membrane
      integrity. We report that moderate fluid percussion injury (FPI) increases levels
      of 4-Hydroxynonenal (HNE), an intermediary for the harmful effects of lipid
      peroxidation on neurons. A more direct action of FPI on membrane homeostasis was
      evidenced by a reduction in calcium-independent phospholipase A2 (iPLA2)
      important for metabolism of membrane phospholipids such as DHA, and an increase
      in the fatty acid transport protein (FATP) involved in translocation of long
      chain fatty acids across the membrane. A potential association between membrane
      disruption and neuronal function was suggested by reduced levels of the NR2B
      subunit of the transmembrane NMDA receptor, in association with changes in iPLA2
      and syntaxin-3 (STX-3, involved in the action of membrane DHA on synaptic
      membrane expansion). In addition, changes in iPLA2, 4-HNE, and STX-3 were
      proportional to reduced performance in a spatial learning task. In turn, the
      dietary supplementation with the curcumin derivative counteracted all the effects
      of FPI, effectively restoring parameters of membrane homeostasis. Results show
      the potential of the curcumin derivative to promote membrane homeostasis
      following TBI, which may foster a new line of non-invasive therapeutic treatments
      for TBI patients by endogenous up-regulation of molecules important for neural
      repair and plasticity.

PMID- 20816822
TI  - Deep brain stimulation of the lateral cerebellar nucleus produces frequency
      specific alterations in motor evoked potentials in the rat in vivo.
AB  - The cerebral cortex is tightly and reciprocally linked to the cerebellum and the
      ascending dentato-thalalmo-cortical pathway influences widespread cortical
      regions. Using a rodent model of middle cerebral artery stroke, we showed
      previously that chronic, 20 Hz stimulation of the contralateral lateral
      cerebellar nucleus (LCN) improved motor recovery, while 50 Hz stimulation did
      not. Using motor evoked potentials (MEP) elicited by intracortical
      microstimulation, we now show the effect of LCN stimulation on motor cortex
      excitability as a function of pulse frequency in propofol-anesthetized rats. MEPs
      were recorded serially, at 15-s intervals, with cerebellar stimulation delivered
      in 10-min blocks at rates of 20, 30, 40, 50 or 100 Hz. Stimulation at 20, 30, 40
      or 50 Hz enhanced the average MEP response across the block, with the maximal
      overall increase observed during 30 Hz stimulation. However, the effect varied as
      a function of both repeated trials within the block and LCN stimulation
      frequency, such that 40 Hz and 50 Hz stimulation showed a reduced effect over
      time. Stimulation at 100 Hz produced a transient increase in MEP amplitude in
      some animals; however the overall effect across the block was a trend towards
      reduced cortical excitability. These results suggest that direct stimulation of
      the LCN can yield frequency-dependent changes in cortical excitability and may
      provide a therapeutic approach to modulating cortical activity for the treatment
      of strokes or other focal cortical lesions, movement disorders and epilepsy.

PMID- 20816823
TI  - Two cytokine signaling molecules co-operate to promote axonal transport and
      growth.
AB  - The neuropoietic cytokines and their cytoplasmic signaling molecules contribute
      to axotomy-induced events in the nerve cell body that are beneficial to axonal
      regeneration. Previous studies have revealed a paradox in that, in vivo,
      suppressor of cytokine signaling (SOCS3) is induced in axotomized primary sensory
      neurons which are in a growth mode but, in vitro, SOCS3 strongly inhibits neurite
      growth from the same neurons. The present studies in cell lines with immuno
      precipitation and western blotting, and Forstner resonance energy transfer showed
      that SOCS3 binds to the C terminus of C-Jun N-terminal kinase-interacting protein
      1 (JIP1), increases its serine phosphorylation, and increases its binding to
      kinesin. Axonal transport was studied in vitro in adult rat primary sensory
      neurons by analyses of recovery of fluorescence after photobleaching and of the
      velocity and direction of movement of organelles. Over-expression of SOCS3 in
      addition to JIP1 had two consequences. First, recovery of fluorescence after
      photobleaching was more rapid and, second, JIP1-containing organelles moved more
      quickly and more frequently in retrograde direction. With respect to neurite
      outgrowth, SOCS3 alone was, as expected, strongly inhibitory but, in the presence
      of excess JIP1 augmented the stimulatory activity of the latter. The observations
      indicate that interactions between JIP1 and SOCS3 influence favorably axonal
      transport and growth in vitro.

PMID- 20816824
TI  - Exposure to extremely low-frequency (50 Hz) electromagnetic fields enhances adult
      hippocampal neurogenesis in C57BL/6 mice.
AB  - Throughout life, new neurons are continuously generated in the hippocampus, which
      is therefore a major site of structural plasticity in the adult brain. We
      recently demonstrated that extremely low-frequency electromagnetic fields
      (ELFEFs) promote the neuronal differentiation of neural stem cells in vitro by up
      regulating Ca(v)1-channel activity. The aim of the present study was to determine
      whether 50-Hz/1 mT ELFEF stimulation also affects adult hippocampal neurogenesis
      in vivo, and if so, to identify the molecular mechanisms underlying this action
      and its functional impact on synaptic plasticity. ELFEF exposure (1 to 7 h/day
      for 7 days) significantly enhanced neurogenesis in the dentate gyrus (DG) of
      adult mice, as documented by increased numbers of cells double-labeled for 5
      bromo-deoxyuridine (BrdU) and doublecortin. Quantitative RT-PCR analysis of
      hippocampal extracts revealed significant ELFEF exposure-induced increases in the
      transcription of pro-neuronal genes (Mash1, NeuroD2, Hes1) and genes encoding
      Ca(v)1.2 channel alpha(1C) subunits. Increased expression of NeuroD1, NeuroD2 and
      Ca(v)1 channels was also documented by Western blot analysis. Immunofluorescence
      experiments showed that, 30 days after ELFEF stimulation, roughly half of the
      newly generated immature neurons had survived and become mature dentate granule
      cells (as shown by their immunoreactivity for both BrdU and NeuN) and were
      integrated into the granule cell layer of the DG. Electrophysiological
      experiments demonstrated that the new mature neurons influenced hippocampal
      synaptic plasticity, as reflected by increased long-term potentiation. Our
      findings show that ELFEF exposure can be an effective tool for increasing in vivo
      neurogenesis, and they could lead to the development of novel therapeutic
      approaches in regenerative medicine.

PMID- 20816825
TI  - The culture of olfactory ensheathing cells (OECs)--a distinct glial cell type.
AB  - Olfactory ensheathing cells (OECs) have become a popular candidate for the
      transplant-mediated repair of the damaged CNS. In this review a description is
      made of the origins of these cells and a historical development of their
      purification and maintenance in culture. In addition, we illustrate the cellular
      and molecular characteristics of OECs and emphasise that although they share many
      properties with Schwann cells, they possess several inherent differences which
      may allow them to be more beneficial for CNS repair. In summary, OECs are
      distinct glial cells and the detailed understanding of their biological and
      molecular properties is essential in ensuring their clinical efficacy after cell
      transplantation. This article is part of a Special Issue entitled: Understanding
      olfactory ensheathing glia and their prospect for nervous system repair.

PMID- 20816826
TI  - Progesterone and allopregnanolone attenuate blood-brain barrier dysfunction
      following permanent focal ischemia by regulating the expression of matrix
      metalloproteinases.
AB  - Blood-brain barrier (BBB) breakdown after stroke is linked to the up-regulation
      of metalloproteinases (MMPs) and inflammation. This study examines the effects of
      progesterone (PROG) and its neuroactive metabolite allopregnanolone (ALLO) on BBB
      integrity following permanent middle cerebral artery occlusion (pMCAO). Rats
      underwent pMCAO by electro-coagulation and received intraperitoneal injections of
      PROG (8 mg/kg), ALLO (8 mg/kg) or vehicle at 1 h post-occlusion and then
      subcutaneous injections (8 mg/kg) at 6, 24, and 48 h. MMP activation and
      expression were analyzed by Western blot, immunohistochemistry and gelatin
      zymography 72 h post-pMCAO. Occludin1, claudin5, tumor necrosis factor-alpha (TNF
      alpha) and Interleukin-6 (IL-6) were analyzed at 72 h post-pMCAO with Western
      blots. BBB permeability was measured by Evans blue extravasation and infarct size
      was evaluated by cresyl violet at 72 h after pMCAO. Ischemic injury significantly
      (p<0.05) increased the expression of MMP-9, MMP-2, TNF-alpha and IL-6, and
      reduced the levels of occludin1 and claudin5. These changes were followed by
      increased infarct size (% contralateral hemisphere) and Evans blue extravasation
      into the brain indicating compromise of the BBB. PROG and ALLO attenuated BBB
      disruption and infarct size following pMCAO by reducing MMPs and the inflammatory
      response and by preventing the degradation of occludin1 and claudin5. We conclude
      that PROG and ALLO can help to protect BBB disruption following pMCAO.

PMID- 20816827
TI  - Species-specific control of cellular proliferation and the impact of large animal
      models for the use of olfactory ensheathing cells and Schwann cells in spinal
      cord repair.
AB  - Autologous transplantation of olfactory ensheathing cells (OECs) and Schwann
      cells (SCs) is considered a promising option to promote axonal regrowth and
      remyelination after spinal cord injury in humans. However, if the experimental
      data from the rodent model can be directly extrapolated to humans, as widely
      believed, remains to be established. While limitations of the rodent system have
      recently been discussed with regard to the distinct organization of the motor
      systems, the question whether OECs and SCs may display species-specific
      properties has not been fully addressed. Prompted by recent studies on canine and
      porcine glia, we performed a detailed analysis of the in vitro and in vivo
      properties of OECs and SCs and show that rodent but not human, monkey, porcine,
      and canine glia require mitogens for in vitro expansion, display a complex
      response to elevated intracellular cAMP, and undergo spontaneous immortalization
      upon prolonged mitogen stimulation. These data indicate fundamental inter-species
      differences of the control of cellular proliferation. Whether OECs and SCs from
      large animals and humans share growth-promoting in vivo properties with their
      rodent counterpart is not yet clear. Autologous implantation studies in humans
      did not reveal adverse effects of cell transplantation so far. However, in vivo
      studies of large animal or human glia and rodent recipients mainly focused on the
      remyelinating potential of the transplanted cells. Thus, further experimental in
      vivo studies in large animals are essential to fully define the axonal growth
      promoting potential of OECs and SCs. Based on the homology of the in vitro growth
      control between porcine, canine and human glia, it is concluded that these
      species may serve as valuable translational models for scaling up human
      procedures. This article is part of a Special Issue entitled: Understanding
      olfactory ensheathing glia and their prospect for nervous system repair.

PMID- 20816828
TI  - Atorvastatin prevents hippocampal cell death, neuroinflammation and oxidative
      stress following amyloid-beta(1-40) administration in mice: evidence for
      dissociation between cognitive deficits and neuronal damage.
AB  - The accumulation of amyloid-beta (Abeta) peptides in the brain of human and
      rodents has been associated with the activation of glial cells, neuroinflammatory
      and oxidative responses, and cognitive deficits. These oxidative changes leave
      glutamate transporters more vulnerable and may result in reduction of their
      functions, resulting in excitotoxic damage. Herein, we evaluated the effects of
      atorvastatin, a HMG-CoA reductase inhibitor, in molecular and behavioral
      alterations induced by a single intracerebroventricular injection of aggregated
      Abeta(1-40) (400 pmol) in mice. An increased glial fibrillar acidic protein
      (GFAP) expression and cyclooxygenase-2 (COX-2) levels, as well as increased lipid
      peroxidation and impairment in the glutathione antioxidant system and cell
      degeneration was found in the hippocampus of Abeta(1-40)-treated mice. Abeta(1
      40) also induced a marked decrease in glutamatergic transporters (GLAST and GLT
      1) expression and in l-[3H] glutamate uptake in mice hippocampus, in addition to
      spatial learning and memory deficits. Atorvastatin (10 mg/kg/day v.o.) was
      administered after Abeta(1-40) injection and through seven consecutive days.
      Atorvastatin treatment was neuroprotective against cell degeneration induced by
      Abeta(1-40), reducing inflammatory and oxidative responses and increasing the
      expression of glutamatergic transporters. On the other hand, atorvastatin did not
      reverse the cognitive impairments and failed to alter the hippocampal glutamate
      uptake in Abeta(1-40)-treated mice. These results reinforce and extend the notion
      of the potential neuroprotective action of atorvastatin against the neuronal
      toxicity induced by Abeta(1-40). In addition, the present findings suggest that
      the spatial learning and memory deficits induced by Abeta peptides in rodents may
      not be entirely related to neuronal damage.

PMID- 20816829
TI  - The role of HER3, the unpretentious member of the HER family, in cancer biology
      and cancer therapeutics.
AB  - Many types of human cancer are characterized by deregulation of the human
      epidermal growth factor receptor (HER) family of tyrosine kinase receptors. In
      some cancers, genomic events causing overactivity of individual HER family
      members are etiologically linked with the pathogenesis of these cancers, and
      constitute the driving signaling function underlying their tumorigenic behavior.
      HER3 stands out among this family as the only member lacking catalytic kinase
      function. Cancers with driving HER3 amplifications or mutations have not been
      found, and studies of its expression in tumors have been only weakly provocative.
      However, substantial evidence, predominantly from experimental models, now
      suggest that its non-catalytic functions are critically important in many cancers
      driven by its' HER family partners. Furthermore, new insights into the mechanism
      of activation in the HER family has provided clear evidence of functionality in
      the HER3 kinase domain. The convergence of structural, mechanistic, and
      experimental evidence highlighting HER3 functions that may be critical in
      tumorigenesis have now led to renewed efforts towards identification of cancers
      or subtypes of cancers wherein HER3 function may be important in tumor
      progression or drug resistance. It appears now that its failure to earn the
      traditional definition of an oncogene has allowed the tumor promoting functions
      of HER3 to elude the effects of cancer therapeutics. But experimental science has
      now unmasked the unpretentious role of HER3 in cancer biology, and the next
      generation of cancer therapies will undoubtedly perform much better because of
      it.

PMID- 20816830
TI  - Cross-talk between light and glucose regulation controls toxin production and
      morphogenesis in Aspergillus nidulans.
AB  - Light is a major environmental stimulus that has a broad effect on organisms,
      triggering a cellular response that results in an optimal adaptation enhancing
      fitness and survival. In fungi, light affects growth, and causes diverse
      morphological changes such as those leading to reproduction. Light can also
      affect fungal metabolism, including the biosynthesis of natural products. In this
      study we show that in Aspergillus nidulans the effect of light on the production
      of the sterigmatocystin (ST) toxin depends on the glucose concentration. In
      cultures grown with 1% glucose and exposed to light, ST production was lower than
      when grown in the dark. This lower ST production coincided with an elevated rate
      of cellular damage with partial loss of nuclear integrity and vacuolated
      cytoplasm. However, in cultures grown with 2% glucose these effects were reversed
      and light enhanced ST production. Glucose abundance also affected the light
      dependent subcellular localization of the VeA (velvet) protein, a key regulator
      necessary for normal light-dependent morphogenesis and secondary metabolism in
      Aspergilli and other fungal genera. The role of other VeA-associated proteins,
      particularly the blue-light-sensing proteins LreA and LreB (WC-1 and WC-2
      orthologs), on conidiation could also be modified by the abundance of glucose. We
      also show that LreA and LreB, as well as the phytochrome FphA, modulate not only
      the synthesis of sterigmatocystin, but also the production of the antibiotic
      penicillin.

PMID- 20816831
TI  - The conserved CXXC motif of hepatic stimulator substance is essential for its
      role in mitochondrial protection in H2O2-induced cell apoptosis.
AB  - Hepatic stimulator substance (HSS) protects liver cells from various toxins by
      alleviating lesions caused in the mitochondria. This paper demonstrates the
      necessity of the conserved CXXC catalytic motif (C62-C65) for the mitochondria
      targeted anti-apoptotic activity of HSS. Mutating the conserved CXXC motif
      eliminated the protective effects against H(2)O(2)-induced apoptosis and
      diminished the protection of the mitochondria. However, the mutation of the other
      disulfide bond C91-C108 mainly preserved the protection of mitochondria by HSS,
      implying that the conserved CXXC motif and sulfhydryl oxidase (SOX) activity are
      essential for mitochondrial protection.

PMID- 20816832
TI  - Effects of inhaled corticosteroids in stable chronic obstructive pulmonary
      disease.
AB  - Chronic obstructive pulmonary disease (COPD) has been described as a
      heterogeneous multifactorial disorder associated with an abnormal inflammatory
      response of the peripheral airways and with variable morphologic, physiologic and
      clinical phenotypes. This notion of the disease is actually poorly supported by
      data, and there are substantial discrepancies and a weak correlation between
      inflammation, structural damage, functional impairment and degree of clinical
      symptoms. This problem is compounded by a poor understanding of the complexity
      and intricacies on the inflammatory pathways in COPD. Despite the evidence for
      efficacy of inhaled corticosteroids (ICS) on selected clinical endpoints in COPD,
      we cannot assume that anti-inflammatory treatment with ICS alone or in
      combination with long-acting bronchodilators will necessarily improve the
      underlying inflammatory processes and patient relevant outcomes in COPD. Given
      the widespread use of inhaled corticosteroids (ICS) alone or in combination for
      the treatment of COPD across all severities, it is important to weigh their
      clinically proven benefits and shortcomings cautiously and critically. Reviewed
      is the current evidence-based role of ICS on inflammatory markers and patient
      relevant outcomes in COPD.

PMID- 20816833
TI  - Rapid onset of bronchodilation with formoterol/beclomethasone Modulite and
      formoterol/budesonide Turbuhaler as compared to formoterol alone in patients with
      COPD.
AB  - In the present study, we examined whether there is a difference in the onset of
      bronchodilatation between formoterol/beclomethasone 12/200 MUg Modulite and
      formoterol/budesonide 9/320 MUg Turbuhaler in patients with COPD. We enrolled 28
      patients with stable COPD. Both formoterol/beclomethasone and
      formoterol/budesonide elicited a larger mean FEV1-AUC0-15min than formoterol
      alone, whereas there was no significant difference between their FEV1-AUC0-15min.
      Also the change in FEV1 15 min after inhalation of formoterol/beclomethasone
      combination or formoterol/budesonide combination was greater than that induced by
      formoterol alone. This study confirms the rapid effect of the inhaled
      corticosteroid component when combined with formoterol and indicates that the
      onset of bronchodilation of formoterol/beclomethasone Modulite and
      formoterol/budesonide Turbuhaler are similar and greater than formoterol alone in
      patients with COPD.

PMID- 20816834
TI  - Klf4 overexpression activates epithelial cytokines and inflammation-mediated
      esophageal squamous cell cancer in mice.
AB  - BACKGROUND & AIMS: Esophageal squamous cell cancer accounts for more than 90% of
      cases of esophageal cancers. Its pathogenesis involves chronic epithelial
      irritation, although the factors involved in the inflammatory process and the
      mechanisms of carcinogenesis are unknown. We sought to develop a mouse model of
      this cancer. METHODS: We used the ED-L2 promoter of Epstein-Barr virus to
      overexpress the transcriptional regulator Kruppel-like factor 4 (Klf4) in
      esophageal epithelia of mice; we used mouse primary esophageal keratinocytes to
      examine the mechanisms by which KLF4 induces cytokine production. RESULTS: KLF4
      was an epithelial-specific mediator of inflammation; we developed a new mouse
      model of esophageal squamous dysplasia and inflammation-mediated squamous cell
      cancer. KLF4 activated a number of proinflammatory cytokines, including TNF
      alpha, CXCL5, G-CSF and IL-1alpha, within keratinocytes in an NF-kappaB-dependent
      manner. KLF4 was not detected in proliferating or cancer cells, indicating a non
      cell autonomous effect of KLF4 on proliferation and carcinogenesis. CONCLUSIONS:
      KLF4 has distinct functions in carcinogenesis; upregulation of Klf4 specifically
      in esophageal epithelial cells induces inflammation. This mouse model might be
      used to determine the molecular mechanisms of esophageal squamous cell cancer and
      inflammation-mediated carcinogenesis.

PMID- 20816835
TI  - A pyrosequencing study in twins shows that gastrointestinal microbial profiles
      vary with inflammatory bowel disease phenotypes.
AB  - BACKGROUND & AIMS: The composition of the gastrointestinal microbiota is thought
      to have an important role in the etiology of inflammatory bowel diseases (IBDs)
      such as Crohn's disease (CD) and ulcerative colitis (UC). Interindividual
      variation and an inability to detect less abundant bacteria have made it
      difficult to correlate specific bacteria with disease. METHODS: We used 454
      pyrotag sequencing to determine the compositions of microbial communities in
      feces samples collected from a cohort of 40 twin pairs who were concordant or
      discordant for CD or UC, and in mucosal samples from a subset of the cohort. The
      cohort primarily comprised patients who were in remission, but also some with
      active disease. RESULTS: The profiles of the microbial community differed with
      disease phenotypes; relative amounts of bacterial populations correlated with IBD
      phenotypes. The microbial compositions of individuals with CD differed from those
      of healthy individuals, but were similar between healthy individuals and
      individuals with UC. Profiles from individuals with CD that predominantly
      involved the ileum differed from those with CD that predominantly involved the
      colon; several bacterial populations increased or decreased with disease type.
      Changes specific to patients with ileal CD included the disappearance of core
      bacteria, such as Faecalibacterium and Roseburia, and increased amounts of
      Enterobacteriaceae and Ruminococcus gnavus. CONCLUSIONS: Bacterial populations
      differ in abundance among individuals with different phenotypes of CD. Specific
      species of bacteria are associated with ileal CD; further studies should
      investigate their role in pathogenesis.

PMID- 20816836
TI  - Induction pegylated interferon alfa-2a and high dose ribavirin do not increase
      SVR in heavy patients with HCV genotype 1 and high viral loads.
AB  - BACKGROUND & AIMS: Patients infected with hepatitis C virus (HCV) genotype 1,
      body weight >=85 kg, and high baseline viral load respond poorly to standard
      doses of pegylated interferon (peginterferon) and ribavirin. We evaluated
      intensified therapy with peginterferon alfa-2a plus ribavirin. METHODS: This
      double-blind randomized trial included HCV genotype 1-infected outpatients from
      hepatology clinics with body weight >=85 kg and HCV RNA titer >=400,000 IU/mL.
      Patients were randomized to 180 MUg/wk peginterferon alfa-2a for 48 weeks plus
      1200 mg/day ribavirin (standard of care) (group A, n = 191) or 1400/1600 mg/day
      ribavirin (group B, n = 189). Additional groups included 360 MUg/wk peginterferon
      alfa-2a for 12 weeks then 180 MUg/wk peginterferon alfa-2a for 36 weeks plus 1200
      mg/day ribavirin (group C, n = 382) or 1400/1600 mg/day ribavirin (group D, n =
      383). Follow-up lasted 24 weeks after treatment. RESULTS: Sustained virologic
      response rates (HCV RNA level <15 IU/mL at end of follow-up) in groups A, B, C,
      and D were 38%, 43%, 44%, and 41%, respectively. There were no significant
      differences among the 4 groups or between pooled peginterferon alfa-2a regimens
      (A + B vs C + D: odds ratio [OR], 1.08; 95% confidence interval [CI], 0.83-1.39;
      P = .584) or pooled ribavirin regimens (A + C vs B + D: OR, 1.00; 95% CI, 0.79
      1.28; P = .974). CONCLUSIONS: In patients infected with HCV genotype 1 who are
      difficult to treat (high viral load, body weight >=85 kg), a 12-week induction
      regimen of peginterferon alfa-2a and/or higher-dose ribavirin is not more
      effective than the standard regimen.

PMID- 20816837
TI  - Intracellular calcium release and protein kinase C activation stimulate sonic
      hedgehog gene expression during gastric acid secretion.
AB  - BACKGROUND & AIMS: Hypochlorhydria during Helicobacter pylori infection inhibits
      gastric Sonic Hedgehog (Shh) expression. We investigated whether acid-secretory
      mechanisms regulate Shh gene expression through intracellular calcium (Ca2(+)(i))
      dependent protein kinase C (PKC) or cyclic adenosine monophosphate (cAMP)
      dependent protein kinase A (PKA) activation. METHODS: We blocked Hedgehog
      signaling by transgenically overexpressing a secreted form of the Hedgehog
      interacting protein-1, a natural inhibitor of hedgehog ligands, which induced
      hypochlorhydria. Gadolinium, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'
      tetraacetic acid (EGTA) + 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic
      acid (BAPTA), PKC-overexpressing adenoviruses, and PKC inhibitors were used to
      modulate Ca(2+)(i)-release, PKC activity, and Shh gene expression in primary
      gastric cell, organ, and AGS cell line cultures. PKA hyperactivity was induced in
      the H(+)/K(+)-beta-cholera-toxin-overexpressing mice. RESULTS: Mice that
      expressed secreted hedgehog-interacting protein-1 had lower levels of gastric
      acid (hypochlorhydria), reduced production of somatostatin, and increased gastrin
      gene expression. Hypochlorhydria in these mice repressed Shh gene expression,
      similar to the levels obtained with omeprazole treatment of wild-type mice.
      However, Shh expression also was repressed in the hyperchlorhydric H(+)/K(+)-beta
      cholera-toxin model with increased cAMP, suggesting that the regulation of Shh
      was not solely acid-dependent, but pertained to specific acid-stimulatory
      signaling pathways. Based on previous reports that Ca(2+)(i) release also
      stimulates acid secretion in parietal cells, we showed that gadolinium-,
      thapsigargin-, and carbachol-mediated release of Ca(2+)(i) induced Shh
      expression. Ca(2+)-chelation with BAPTA + EGTA reduced Shh expression.
      Overexpression of PKC-alpha, -beta, and -delta (but not PKC-epsilon) induced an
      Shh gene expression. In addition, phorbol esters induced a Shh-regulated reporter
      gene. CONCLUSIONS: Secretagogues that stimulate gastric acid secretion induce Shh
      gene expression through increased Ca(2+)(i)-release and PKC activation. Shh might
      be the ligand transducing changes in gastric acidity to the regulation of G-cell
      secretion of gastrin.

PMID- 20816839
TI  - HIV-Tat-mediated delivery of an LPTS functional fragment inhibits telomerase
      activity and tumorigenicity of hepatoma cells.
AB  - BACKGROUND & AIMS: Human liver-related putative tumor suppressor (LPTS) is a gene
      that encodes a telomerase inhibitory protein that is similar to human Pin2/TRF1
      interacting protein. The LPTS protein binds directly to the telomerase catalytic
      subunit (human telomerase reverse transcriptase) and suppresses telomerase
      activity. Telomere maintenance and telomerase activity are required for long-term
      proliferation of cancer cells, so LPTS might be used in anticancer strategies.
      METHODS: The carboxy-terminal (functional) fragment of LPTS was fused to the
      transactivator of transcription of human immunodeficiency virus (Tat)-an 11-amino
      acid peptide that translocates across the cell membrane; the TAT-fused C-terminal
      of LPTS (TAT-LPTS-LC) was purified and transduced into cells. Telomerase activity
      was identified by using the telomeric repeat amplification protocol. The effects
      of the TAT-LPTS-LC protein on cell proliferation and death were evaluated by
      colorimetric tetrazolium salt and flow cytometry analyses. Tumor growth was
      analyzed in nude mice. RESULTS: The purified TAT-LPTS-LC protein was efficiently
      delivered into the cells, where it suppressed telomerase activity and shortened
      telomere length. TAT-LPTS-LC inhibited proliferation of telomerase-positive
      hepatocellular carcinoma BEL-7404 and hepatoblastoma HepG2cells and induced their
      death; however, it had no effect on telomerase-negative liver cell line L02 and
      osteosarcoma cell line Saos-2. In mice, tumor formations by BEL-7404 cells were
      suppressed by TAT-LPTS-LC treatments. CONCLUSIONS: Transduction of hepatoma cells
      with a fusion protein that contains the C-terminal, functional fragment of LPTS
      and human immunodeficiency virus Tat (TAT-LPTS-LC) causes telomere shortening,
      limits proliferation, and inhibits growth of tumors from these cells in mice. TAT
      LPTS-LC inhibits telomerase activity and might be developed as an anticancer
      agent.

PMID- 20816840
TI  - Metabolome, transcriptome and metabolic flux analysis of arabinose fermentation
      by engineered Saccharomyces cerevisiae.
AB  - One of the challenges in strain improvement by evolutionary engineering is to
      subsequently determine the molecular basis of the improved properties that were
      enriched from the natural genetic variation during the selective conditions. This
      study focuses on Saccharomyces cerevisiae IMS0002 which, after metabolic and
      evolutionary engineering, ferments the pentose sugar arabinose. Glucose- and
      arabinose-limited anaerobic chemostat cultures of IMS0002 and its non-evolved
      ancestor were subjected to transcriptome analysis, intracellular metabolite
      measurements and metabolic flux analysis. Increased expression of the GAL-regulon
      and deletion of GAL2 in IMS0002 confirmed that the galactose transporter is
      essential for growth on arabinose. Elevated intracellular concentrations of
      pentose-phosphate-pathway intermediates and upregulation of TKL2 and YGR043c
      (encoding transketolase and transaldolase isoenzymes) suggested an involvement of
      these genes in flux-controlling reactions in arabinose fermentation. Indeed,
      deletion of these genes in IMS0002 caused a 21% reduction of the maximum specific
      growth rate on arabinose.

PMID- 20816838
TI  - XBP1 controls maturation of gastric zymogenic cells by induction of MIST1 and
      expansion of the rough endoplasmic reticulum.
AB  - BACKGROUND & AIMS: The transition of gastric epithelial mucous neck cells (NCs)
      to digestive enzyme-secreting zymogenic cells (ZCs) involves an increase in rough
      endoplasmic reticulum (ER) and formation of many large secretory vesicles. The
      transcription factor MIST1 is required for granulogenesis of ZCs. The
      transcription factor XBP1 binds the Mist1 promoter and induces its expression in
      vitro and expands the ER in other cell types. We investigated whether XBP1
      activates Mist1 to regulate ZC differentiation. METHODS: Xbp1 was inducibly
      deleted in mice using a tamoxifen/Cre-loxP system; effects on ZC size and
      structure (ER and granule formation) and gastric differentiation were studied and
      quantified for up to 13 months after deletion using morphologic,
      immunofluorescence, quantitative reverse-transcriptase polymerase chain reaction,
      and immunoblot analyses. Interactions between XBP1 and the Mist1 promoter were
      studied by chromatin immunoprecipitation from mouse stomach and in XBP1
      transfected gastric cell lines. RESULTS: Tamoxifen-induced deletion of Xbp1
      (Xbp1Delta) did not affect survival of ZCs but prevented formation of their
      structure. Xbp1Delta ZCs shrank 4-fold, compared with those of wild-type mice,
      with granulogenesis and cell shape abnormalities and disrupted rough ER. XBP1 was
      required and sufficient for transcriptional activation of MIST1. ZCs that
      developed in the absence of XBP1 induced ZC markers (intrinsic factor, pepsinogen
      C) but showed abnormal retention of progenitor NC markers. CONCLUSIONS: XBP1
      controls the transcriptional regulation of ZC structural development; it expands
      the lamellar rough ER and induces MIST1 expression to regulate formation of large
      granules. XBP1 is also required for loss of mucous NC markers as ZCs form.

PMID- 20816841
TI  - Testosterone and cortisol jointly regulate dominance: evidence for a dual-hormone
      hypothesis.
AB  - Traditional theories propose that testosterone should increase dominance and
      other status-seeking behaviors, but empirical support has been inconsistent. The
      present research tested the hypothesis that testosterone's effect on dominance
      depends on cortisol, a glucocorticoid hormone implicated in psychological stress
      and social avoidance. In the domains of leadership (Study 1, mixed-sex sample)
      and competition (Study 2, male-only sample), testosterone was positively related
      to dominance, but only in individuals with low cortisol. In individuals with high
      cortisol, the relation between testosterone and dominance was blocked (Study 1)
      or reversed (Study 2). Study 2 further showed that these hormonal effects on
      dominance were especially likely to occur after social threat (social defeat).
      The present studies provide the first empirical support for the claim that the
      neuroendocrine reproductive (HPG) and stress (HPA) axes interact to regulate
      dominance. Because dominance is related to gaining and maintaining high status
      positions in social hierarchies, the findings suggest that only when cortisol is
      low should higher testosterone encourage higher status. When cortisol is high,
      higher testosterone may actually decrease dominance and in turn motivate lower
      status.

PMID- 20816842
TI  - Megakaryoblastic leukemia protein-1 (MKL1): Increasing evidence for an
      involvement in cancer progression and metastasis.
AB  - Megakaryoblastic leukemia protein-1 (MKL1), also termed MAL, MRTF-A, and BSAC,
      belongs to the MRTF family of transcription factors that share evolutionary
      conserved domains required for actin-binding, homo- and heterodimerization, high
      order chromatin organization and transcriptional activation. MKL1 regulates many
      processes, including muscle cell differentiation, cardiovascular development,
      remodeling of neuronal networks in the developing and adult brain, megakaryocytic
      differentiation and migration, modulation of cellular motile functions and
      epithelial-mesenchymal transition. Moreover, deregulation by genetic alterations
      and/or altered expression of MKL1 can contribute to a number of pathological
      processes such as coronary artery disease, sarcopenia, acute megakaryoblastic
      leukemia, and cancer. In this article, we review the structure, regulation and
      biological functions of MKL1. In addition, we discuss recent evidence that
      strongly suggests a dual role for MKL1 in oncogenic mechanisms, as a tumor
      promoting or tumor-suppressing molecule. Future studies will be necessary to
      evaluate the potential clinical implications of MKL1 expression and activation in
      cancer.

PMID- 20816844
TI  - The progression of the intra-erythrocytic cell cycle of Plasmodium falciparum and
      the role of the centriolar plaques in asynchronous mitotic division during
      schizogony.
AB  - The cell division cycle and mitosis of intra-erythrocytic (IE) Plasmodium
      falciparum are poorly understood aspects of parasite development which affect
      malaria molecular pathogenesis. Specifically, the timing of the multiple gap (G),
      DNA synthesis (S) and chromosome separation (M) phases of parasite mitosis are
      not well defined, nor whether genome divisions are immediately followed by
      cleavage of the nuclear envelope. Curiously, daughter merozoite numbers do not
      follow the geometric expansion expected from equal numbers of binary divisions,
      an outcome difficult to explain using the standard model of cell cycle
      regulation. Using controlled synchronisation techniques, confocal microscopy to
      visualise key organelles and fluorescence in situ hybridization (FISH) to follow
      the movements and replication of genes and telomeres, we have re-analysed the
      timing and progression of mitotic events. The asynchronous duplications of the P.
      falciparum centrosome equivalents, the centriolar plaques, are established and
      these are correlated with chromosome and nuclear divisions in a new model of P.
      falciparum schizogony. Our results improve the resolution of the cell cycle and
      its phases during P. falciparum IE development, showing that asynchronous,
      independent nuclear division occurs during schizogony, with the centriolar
      plaques playing a major role in regulating mitotic progression.

PMID- 20816843
TI  - Plasmodium immunomics.
AB  - The Plasmodium parasite, the causative agent of malaria, is an excellent model
      for immunomic-based approaches to vaccine development. The Plasmodium parasite
      has a complex life cycle with multiple stages and stage-specific expression of
      ~5300 putative proteins. No malaria vaccine has yet been licensed. Many believe
      that an effective vaccine will need to target several antigens and multiple
      stages, and will require the generation of both antibody and cellular immune
      responses. Vaccine efforts to date have been stage-specific and based on only a
      very limited number of proteins representing <0.5% of the genome. The recent
      availability of comprehensive genomic, proteomic and transcriptomic datasets from
      human and selected non-human primate and rodent malarias provide a foundation to
      exploit for vaccine development. This information can be mined to identify
      promising vaccine candidate antigens, by proteome-wide screening of antibody and
      T cell reactivity using specimens from individuals exposed to malaria and
      technology platforms such as protein arrays, high throughput protein production
      and epitope prediction algorithms. Such antigens could be incorporated into a
      rational vaccine development process that targets specific stages of the
      Plasmodium parasite life cycle with immune responses implicated in parasite
      elimination and control. Immunomic approaches which enable the selection of the
      best possible targets by prioritising antigens according to clinically relevant
      criteria may overcome the problem of poorly immunogenic, poorly protective
      vaccines that has plagued malaria vaccine developers for the past 25 years.
      Herein, current progress and perspectives regarding Plasmodium immunomics are
      reviewed.

PMID- 20816845
TI  - Gene deletion from Plasmodium falciparum using FLP and Cre recombinases:
      implications for applied site-specific recombination.
AB  - The ability to manipulate the genome and induce site-specific recombination using
      either Flippase (FLP) or Cre recombinase has been useful in many systems
      including Plasmodium berghei for specific deletion events or to obtain
      conditional gene expression. To test whether these recombinases are active in
      Plasmodium falciparum we constructed gene knockouts that contain sequences
      recognised as templates for site-specific recombination. We tested the ability of
      FLP and Cre recombinases, expressed conditionally in P. falciparum, to mediate
      deletion of the human dihydrofolate reductase (hdhfr) drug resistance gene. We
      show that Cre recombinase is capable of efficient removal of hdhfr by site
      specific recombination. In contrast, FLP recombinase is very inefficient, even at
      the optimum temperature of 30 degrees C for this enzyme. These results
      demonstrate that Cre recombinase can be utilised in P. falciparum for deletion of
      specific sequences such as drug resistance genes. This can be exploited for
      recycling of drug resistance cassettes and for the design of specific
      recombination events in P. falciparum.

PMID- 20816846
TI  - Reduced activity of the epithelial sodium channel in malaria-induced pulmonary
      oedema in mice.
AB  - Lung complications during malaria infection can range from coughs and impairments
      in gas transfer to the development of acute respiratory distress syndrome (ARDS).
      Infecting C57BL/6 mice with Plasmodium berghei K173 strain (PbK) resulted in
      pulmonary oedema, capillaries congested with leukocytes and infected red blood
      cells (iRBCs), and leukocyte infiltration into the lungs. This new model of
      malaria-associated lung pathology, without any accompanying cerebral
      complications, allows the investigation of mechanisms leading to the lung
      disease. The activity of the amiloride-sensitive epithelial sodium channel (ENaC)
      in alveolar epithelial cells is decreased by several respiratory tract pathogens
      and this is suggested to contribute to pulmonary oedema. We show that PbK, a
      pathogen that remains in the circulation, also decreased the activity and
      expression of ENaC, suggesting that infectious agents can have indirect effects
      on ENaC activity in lung epithelial cells. The reduced ENaC activity may
      contribute to the pulmonary oedema induced by PbK malaria.

PMID- 20816847
TI  - Genotoxic and cytotoxic effects of the formulated insecticide Aficida on
      Cnesterodon decemmaculatus (Jenyns, 1842) (Pisces: Poeciliidae).
AB  - The acute toxicity, genotoxicity, and cytotoxicity of the pirimicarb-containing
      commercial-formulation carbamate insecticide Aficida (50% pirimicarb) were
      evaluated on Cnesterodon decemmaculatus (Pisces, Poeciliidae) exposed under
      laboratory conditions. Micronucleus (MN) induction as well as alterations in the
      erythrocytes:erythroblasts ratios were employed as end-points for genotoxicity
      and cytotoxicity, respectively. Cr(VI) and cyclophosphamide were used as positive
      controls for the toxicity and geno-cytotoxicity assays, respectively. Mean values
      of 344.3 and 225.5mg Aficida((r))/L were determined for LC-50(24h) and LC
      50(96h), respectively. In 48h-exposed fish, a MN increase was found in Aficida
      treated fish in the 50-157mg/L concentration range. When fish were exposed to
      Aficida for 96h, only those animals treated at 50-100mg/L showed an increase in
      MN frequency. Cellular cytotoxicity, revealed by a decreased proportion of
      circulating erythrocytes and an enhancement of erythroblasts, was found after 48h
      of exposure in 50-157mg Aficida/L-treated fish, while, after 96h exposure, only
      100-157mg Aficida/L induced the same effect. This species provides a useful
      experimental model for the biomonitoring of aquatic ecosystems.

PMID- 20816849
TI  - Effects of insulin and clonazepam on DNA damage in diabetic rats submitted to the
      forced swimming test.
AB  - Diabetes mellitus (DM) is a chronic hyperglycemic state. DM may be associated
      with moderate cognitive deficits and neurophysiologic/structural changes in the
      brain (diabetic encephalopathy). Psychiatric manifestations seem to accompany
      this encephalopathy, since the prevalence of depression in diabetic patients is
      much higher than in the general population, and clonazepam is being used to treat
      this complication. The excessive production of oxygen free radicals that may
      occur in diabetes induces a variety of lesions in macromolecules, including DNA.
      In this work, we analyzed DNA damage in leukocytes from streptozotocin-induced
      diabetic rats submitted to the forced swimming test. The DNA damage index was
      significantly elevated (DI=61.00 +/- 4.95) in the diabetic group compared to the
      control group (34.00 +/- 1.26). Significant reductions of the damage index were
      observed in diabetic animals treated with insulin (45.00 +/- 1.82), clonazepam
      (52.00 +/- 1.22), or both agents (39.00 +/- 5.83, not significantly different
      from control levels). Insulin plus clonazepam can protect against DNA damage in
      stressed diabetic rats.

PMID- 20816848
TI  - Characterization and detection of cellular and proteomic alterations in stable
      stathmin-overexpressing, taxol-resistant BT549 breast cancer cells using offgel
      IEF/PAGE difference gel electrophoresis.
AB  - Stathmin/oncoprotein 18, a protein that regulates microtubule dynamics, is highly
      expressed in a number of tumors including leukemia, lymphoma, neuroblastoma,
      breast, ovarian, and prostate cancers. High stathmin levels have been associated
      with the development of resistance to the widely used anti-cancer drug taxol
      (((r))Taxol, paclitaxel). The mechanisms of stathmin-mediated taxol resistance
      are not well-understood at the molecular level. To better understand the role of
      stathmin in taxol resistance, we stably overexpressed stathmin twofold in BT549
      human breast cancer cells and characterized several cell processes involved in
      the mechanism of action of taxol. After stable overexpression of stathmin,
      neither the cell doubling time nor the mitotic index was altered and the
      microtubule polymer mass was reduced only modestly (by 18%). Unexpectedly,
      microtubule dynamicity was reduced by 29% after stathmin overexpression,
      resulting primarily from reduction in the catastrophe frequency. Sensitivity to
      taxol was reduced significantly (by 44%) in a clonogenic assay, and stathmin
      appeared to protect the cells from the spindle-damaging effects of taxol. The
      results suggest that in the stably stathmin-overexpressing clones, compensatory
      gene expression occurred that resulted in normal rates of cell proliferation and
      prevented the increase in catastrophe frequency expected in response to stathmin.
      Stathmin overexpression protected the cells from taxol-induced abnormal mitoses,
      and thus induced taxol resistance. Using offgel IEF/PAGE difference gel
      electrophoresis, we identified a number of proteins whose expression is reduced
      in the taxol-resistant stathmin-overexpressing cell lines, including proteins
      involved in the cytoskeleton and cell structure, the stress response, protein
      folding, glycolysis, and catalysis.

PMID- 20816851
TI  - Timing of eclosion affects diapause development, fat body consumption and
      longevity in Osmia lignaria, a univoltine, adult-wintering solitary bee.
AB  - Most insects from temperate areas enter diapause ahead of winter. Species
      diapausing in a feeding stage and accumulating metabolic reserves during
      permissive pre-wintering conditions are expected to enter diapause shortly before
      the onset of winter. In contrast, species diapausing in a non-feeding stage are
      expected to lower their metabolism as soon as possible to avoid excessive
      consumption of metabolic reserves. The solitary bee Osmia lignaria winters as a
      non-feeding adult within its cocoon, but previous studies show important weight
      losses and increased winter mortality in populations pre-wintered for extended
      periods. We measured respiration rates to assess diapause initiation and
      maintenance during pre-wintering, and tested whether timing of adult eclosion
      affected fitness by measuring fat body depletion, winter mortality and post
      winter longevity. We worked with different cohorts of a population reared under
      natural conditions, and manipulated pre-wintering duration in a population reared
      under artificial conditions. In agreement with our expectation, O. lignaria lower
      their metabolic rates within a few days of adult eclosion, but nonetheless suffer
      strong weight loss during pre-wintering. Early developing individuals suffer
      greater weight loss and fat body depletion, and have short post-winter longevity.
      Although, we found no differences in winter mortality among treatments, our
      results indicate that increased mortality may occur in years with late winter
      arrivals. We discuss fundamental ecophysiological differences between adult and
      prepupal diapause within the Megachilidae, and hypothesize that species wintering
      as adults will be more negatively affected by a situation of extended summers
      under a scenario of global warming.

PMID- 20816850
TI  - Differential expression, phosphorylation of COX subunit 1 and COX activity during
      diapause phase in the cotton bollworm, Helicoverpa armigera.
AB  - Helicoverpa armigera (Lepidoptera, Noctuidae) is an important agricultural pest
      with a pupal diapause. Cytochrome c oxidase (COX) is a key speed-limited enzyme
      of oxidative phosphorylation in mitochondria for ATP production. A differentially
      expressed cDNA fragment encoding COX subunit 1 (cox1) was cloned by differential
      display-PCR from the pupal brain at diapause termination with an injection of
      ecdysone. We then obtained the full length of H. armigera cox1 (Hea-cox1) cDNA
      which has an open reading frame of 1530 nucleotides encoding a putative protein
      of 510 amino acid residues, with CGA as a start codon. To evaluate the response
      to different energy demands during pupal development and at diapause termination,
      we assessed the expression of Hea-cox1 mRNA and protein, COX activity and its
      phosphorylation. The results show that Hea-cox1 expression at the mRNA and
      protein levels is associated with COX activity, and high levels of Hea-cox1
      expression and COX activity are present in nondiapause pupae, suggesting that low
      energy metabolism provided by oxidative phosphorylation in mitochondria in
      diapause individuals is necessary. After diapause is broken by injection of 20
      hydroxyecdysone, expression of Hea-cox1 mRNA and protein increases gradually and
      COX activity increases significantly. Furthermore, Hea-cox1 phosphorylation is
      closely correlated with COX activity, suggesting that reversible protein
      phosphorylation may play a key role in insect diapause by suppressing the rate of
      energy production.

PMID- 20816852
TI  - The Hsp70 chaperones of the Tritryps are characterized by unusual features and
      novel members.
AB  - Proteins belonging to the Hsp70 class of molecular chaperones are highly
      conserved and ubiquitous, performing an essential role in the maintenance of
      cellular homeostasis in almost all known organisms. Trypanosoma brucei,
      Trypanosoma cruzi and Leishmania major are human parasites collectively known as
      the Tritryps. The Tritryps undergo extensive morphological changes during their
      life cycles, largely triggered by the marked differences between conditions in
      their insect vector and human host. Hsp70s are synthesised in response to these
      marked changes in environment and are proposed to be required for these parasites
      to successfully transition between differentiation stages while remaining viable
      and infective. While the Tritryps Hsp70 complement consists of homologues of all
      the major eukaryotic Hsp70s, there are a number of novel members, and some unique
      structural features. This review critically evaluates the current knowledge on
      the Tritryps Hsp70 proteins with an emphasis on T. brucei, and highlights some
      novel and previously unstudied aspects of these multifaceted molecular
      chaperones.

PMID- 20816853
TI  - Zebrafish fat-free, a novel Arf effector, regulates phospholipase D to mediate
      lipid and glucose metabolism.
AB  - Zebrafish fat-free mutants (ffr) exhibit defective intestinal lipid metabolism
      and fat-free protein (Ffr) is involved in Golgi-related vesicular trafficking. In
      this study, we show that ffr mutants also display defective glucose metabolism.
      Using microarray and real-time PCR, we found that a ffr mutant with a nonsense
      mutation exhibits increased transcript level of ADP-ribosylation factor gene
      (arfs). Further analysis indicated that Ffr contains a putative Arf binding motif
      and can bind GTP-bound Arfs. In addition, ffr exhibited increased transcript and
      activity levels of the Arf downstream effector phospholipase D (PLD). Inhibition
      of PLD partially restored lipid and glucose metabolism in ffr, suggesting that
      Ffr is involved in a pathway regulating PLD activity by regulating Arfs. We
      propose that local over-production of phosphatidic acid (PA) by excess PLD
      promotes membrane curvature, which affects Golgi membrane structure and secretory
      processes, contributing to impairment of lipid and glucose metabolism.

PMID- 20816854
TI  - IL-2 induces conformational changes in its preassembled receptor core, which then
      migrates in lipid raft and binds to the cytoskeleton meshwork.
AB  - While interleukin (IL)-2 clearly initiates the sequential assembly of its soluble
      receptor fragments (sIL-2R) in vitro (with sIL-2Ralpha first, sIL-2Rbeta second,
      and sgammac last), the assembly mechanism of full-length subunits (IL-2R) at the
      surface of living lymphocytes remains to be elucidated. Here we demonstrate by
      fluorescence cross-correlated spectroscopy that native IL-2Rbeta and gammac
      assemble spontaneously at the surface of living human leukemia T cells (Kit-225
      cell line) in the absence of IL-2 and with 1:1 stoichiometry. The dissociation
      constant of the membrane-embedded IL-2Rbeta/gammac complex is measured in situ.
      Forster fluorescence resonance energy transfer analyzed by confocal microscopy of
      transfected COS-7 cells between combination pairs of various-length receptor
      chain constructions, using green fluorescent protein derivatives as cytoplasmic
      carboxy-terminal extensions, showed that IL-2Rbeta:ECFP and gammac:EYFP bind each
      other through their extracellular domains, and that IL-2 binding brings their
      transmembrane domains 30 A closer together. These observations demonstrate that
      IL-2Rbeta/gammac heterodimers are preformed and that their cytoplasmic domains,
      carrying Janus kinase (Jak) 1 and Jak3, are pulled and tethered together on
      cytokine binding, triggering signaling transduction. IL-2 binding stabilizes IL
      2/IL-2R complexes in membrane nanodomains that promote Jak1/Jak3 phosphorylation.
      The complexes then interact with the cytoskeleton, which slows receptor diffusion
      (as measured by fluorescence cross-correlated spectroscopy) and promotes STAT
      (signal transducer and activator of transcription) 5 phosphorylation. Separation
      of IL-2-activated receptors from Triton-lysed cells in detergent-resistant
      membrane nanodomains by ultracentrifugation on a sucrose gradient confirmed their
      presence in lipid rafts. The release of the IL-2-activated receptor from
      cytochalasin-treated cells and the IL-2-induced recruitment of actin and tubulin,
      analyzed by immunoprecipitation, confirmed that the activated receptor interacts
      with the cytoskeleton. Although IL-2Ralpha (the third chain that gives the IL
      2Rbeta/gammac receptor core its high affinity for IL-2) is highly expressed at
      the cell surface and mainly clustered in membrane microdomains at the surface of
      Kit-225 cells, the few free IL-2Ralpha present bind last to the IL-2/IL
      2Rbeta/gammac complex and lock IL-2 to its binding site for prolonged action,
      promoting signal amplification.

PMID- 20816855
TI  - Disambiguation in the biomedical domain: the role of ambiguity type.
AB  - Word Sense Disambiguation (WSD), the automatic identification of the meanings of
      ambiguous terms in a document, is an important stage in text processing. We
      describe a WSD system that has been developed specifically for the types of
      ambiguities found in biomedical documents. This system uses a range of knowledge
      sources. It employs both linguistic features, such as local collocations, and
      features derived from domain-specific knowledge sources, the Unified Medical
      Language System (UMLS) and Medical Subject Headings (MeSH). This system is
      applied to three types of ambiguities found in Medline abstracts: ambiguous
      terms, abbreviations with multiple expansions and names that are ambiguous
      between genes. The WSD system is applied to the standard NLM-WSD data set, which
      consists of ambiguous terms from Medline abstracts, and was found to perform well
      in comparison with previously reported results. The system's performance and the
      contribution of each knowledge source depends upon the type of lexical ambiguity.
      87.9% of the ambiguous terms are correctly disambiguated using a combination of
      linguistic features and MeSH terms, 99% of abbreviations are disambiguated by
      combining all knowledge sources, while 97.2% of ambiguous gene names are
      disambiguated using the MeSH terms alone. Analysis reveals that these differences
      are caused by the nature of each ambiguity type. These results should be taken
      into account when deciding which information to use for WSD and the level of
      performance that can be expected.

PMID- 20816856
TI  - A lubrication analysis of pharyngeal peristalsis: application to flavour release.
AB  - After eating a liquid or a semi-liquid food product, a thin film responsible for
      the dynamic profile of aroma release coats the pharyngeal mucosa. The aim of this
      article was to analyse the fluid mechanics of pharyngeal peristalsis and to
      develop a simple biomechanical model in order to understand the role of saliva
      and food bolus viscosity on the coating of pharyngeal mucosa. We began by
      analysing the physiology and the biomechanics of swallowing in order to determine
      relevant model assumptions. This analysis of the literature clarified the types
      of mechanical solicitations applied on the food bolus. Moreover, we showed that
      the pharyngeal peristalsis in the most occluded region is equivalent to a forward
      roll coating process, the originality of which is lubrication by a film of
      saliva. A model based on the lubrication theory for Newtonian liquids was
      developed in dimensionless form. The parametric study showed the strong influence
      of relative saliva thickness on the food bolus coating. A specific experimental
      device was designed that confirms the model predictions. Two sets of conditions
      that depend on the relative thickness of saliva were distinguished. The first is
      characterised by a relatively thin film of saliva: food bolus viscosity has a
      strong impact on mucosa coating. These phenomena are well represented by the
      model developed here. The second is obtained when the saliva film is relatively
      thick: hydrodynamic mixing with saliva, interdiffusion or instabilities may
      govern mucosa coating. Finally, these results were extrapolated to determine the
      influence of food bolus viscosity on the dynamic profile of flavour release
      according to physiological parameters.

PMID- 20816857
TI  - Quantifying the interaction structure and the topological importance of species
      in food webs: a signed digraph approach.
AB  - Due to the structural complexity of nature, it is not always easy to identify
      topologically importance species in an ecosystem. In the past decade, several
      studies in ecology have developed methods for measuring species importance basing
      on direct and indirect inter-specific interactions. Here, by extending a
      previously developed methodology, we present an approach that can quantify the
      interaction structure of a food web and consequently the topological importance
      of species when the food web is viewed as a signed digraph. The basic principle
      behind our approach is to determine the sign and strength of direct and indirect
      interactions for all pathways up to a predefined number of steps. Our approach
      mainly differs from the previous methodology in that we are able to quantify the
      strength of inter-specific interaction as well as in what way species interact
      with each other, as it can explicitly quantify a wide range of ecological
      interactions such as cascading effect, indirect food supply effect, apparent and
      exploitive competitions in the same framework. This then allows us to quantify
      the topological importance of a species and examine whether it is a predominately
      positive or negative interactor in a food web. Furthermore, our analysis reveals
      that positive and negative effects from one species on others eventually cancel
      each other out for longer pathways resulting in stable interaction structure.
      Applications of our methodology include providing a more informative index for
      conservation biologists, and the potential use of interaction structure derived
      from our approach in food web robustness studies is also discussed.

PMID- 20816859
TI  - Image of the month. Skin discoloration from compulsive bathing in a patient with
      hyperemesis syndrome.

PMID- 20816858
TI  - Norfloxacin therapy for hepatopulmonary syndrome: a pilot randomized controlled
      trial.
AB  - BACKGROUND & AIMS: The hepatopulmonary syndrome occurs in up to one-third of
      patients with cirrhosis. Animal models of this disease suggest that endotoxemia
      might cause nitric oxide-mediated vascular dilatation that can be inhibited by
      the antibiotic norfloxacin. We sought to test this hypothesis in humans. METHODS:
      We conducted a pilot randomized, controlled crossover trial of norfloxacin 400 mg
      twice daily for 4 weeks with a 4-week washout period to assess the feasibility of
      a larger trial. The primary clinical end point was change in alveolar-arterial
      oxygen gradient (AaDO2). RESULTS: Recruitment was challenging, and change in
      AaDO2 was highly variable. We recruited 9 adults (1 woman; age, 60 +/- 9 years;
      AaDO2, 50 +/- 22 mm Hg). AaDO2 decreased by 0.8 +/- 4.8 and 3.4 +/- 12.4 mm Hg
      while on norfloxacin and placebo, respectively (P = .59). CONCLUSIONS:
      Recruitment difficulties and variability of the primary outcome measure suggest
      the need for a multicenter clinical research network for future therapeutic
      trials in this disease. There was no major effect of norfloxacin on gas exchange
      in patients with hepatopulmonary syndrome.

PMID- 20816860
TI  - Neither long-term statin use nor atherosclerotic disease is associated with risk
      of colorectal cancer.
AB  - BACKGROUND & AIMS: Statin use has been reported to reduce risk for colorectal
      cancer (CRC) whereas atherosclerotic disease has been reported to increase risk,
      but findings have been inconsistent. We aimed to establish the association of
      statin use and coronary atherosclerosis with CRC. METHODS: We performed a
      population-based case control study of patients with a first diagnosis of CRC
      cancer between January 1, 1991, and December 31, 2008 (n = 9979), using the
      Danish National Registry of Patients. As many as 10 population controls were
      matched to each patient using risk set sampling (n = 99,790). Statin use before
      cancer diagnosis (or control index date) was determined via county prescription
      databases and evidence of coronary atherosclerosis using International
      Classification of Diseases codes. We calculated incidence rate ratios using
      conditional logistic regression, adjusted for multiple covariates. RESULTS: Among
      patients with CRC, statin use was modest (7.7%), but 23.5% of use was long term
      (>=5 years). Ever use of statins (>=2 prescriptions) slightly reduced CRC risk,
      compared with relative to never/rare use (incidence rate ratio [IRR] = 0.87, 95%
      confidence interval = 0.80-0.96). However, long-term use did not affect risk
      compared with never/rare use (IRR = 0.95, 95% 0.80-1.12). No associations were
      observed between atherosclerosis, myocardial infarction, or stroke, and CRC
      incidence. CONCLUSIONS: Although there is a weak inverse association between ever
      use of statins and CRC incidence, there was no trend with increasing duration of
      use, so statins do not appear to reduce CRC risk. We did not confirm the reported
      association between atherosclerosis and CRC risk.

PMID- 20816861
TI  - Image of the month. Fulminant hepatic failure caused by Amanita phalloides
      toxicity.

PMID- 20816862
TI  - Do all patients with documented infected necrosis require necrosectomy/drainage?

PMID- 20816863
TI  - A splenic artery aneurysm that mimics a stromal tumor and causes hematemesis.

PMID- 20816864
TI  - Gastrointestinal bleeding from Brunner gland hamartoma.

PMID- 20816865
TI  - On multistability of delayed genetic regulatory networks with multivariable
      regulation functions.
AB  - Many genetic regulatory networks (GRNs) have the capacity to reach different
      stable states. This capacity is defined as multistability which is an important
      regulation mechanism. Multiple time delays and multivariable regulation functions
      are usually inevitable in such GRNs. In this paper, multistability of GRNs is
      analyzed by applying the control theory and mathematical tools. This study is to
      provide a theoretical tool to facilitate the design of synthetic gene circuit
      with multistability in the perspective of control theory. By transforming such
      GRNs into a new and uniform mathematical formulation, we put forward a general
      sector-like regulation function that is capable of quantifying the regulation
      effects in a more precise way. By resorting to up-to-date techniques, a novel
      Lyapunov-Krasovskii functional (LKF) is introduced for achieving delay dependence
      to ensure less conservatism. New conditions are then proposed to ensure the
      multistability of a GRN in the form of linear matrix inequalities (LMIs) that are
      dependent on the delays. Our multistability conditions are applicable to several
      frequently used regulation functions especially the multivariable ones. Two
      examples are employed to illustrate the applicability and usefulness of the
      developed theoretical results.

PMID- 20816866
TI  - Analytical models approximating individual processes: a validation method.
AB  - Upscaling population models from fine to coarse resolutions, in space, time
      and/or level of description, allows the derivation of fast and tractable models
      based on a thorough knowledge of individual processes. The validity of such
      approximations is generally tested only on a limited range of parameter sets. A
      more general validation test, over a range of parameters, is proposed; this would
      estimate the error induced by the approximation, using the original model's
      stochastic variability as a reference. This method is illustrated by three
      examples taken from the field of epidemics transmitted by vectors that bite in a
      temporally cyclical pattern, that illustrate the use of the method: to estimate
      if an approximation over- or under-fits the original model; to invalidate an
      approximation; to rank possible approximations for their qualities. As a result,
      the application of the validation method to this field emphasizes the need to
      account for the vectors' biology in epidemic prediction models and to validate
      these against finer scale models.

PMID- 20816867
TI  - Mathematical modeling of monolignol biosynthesis in Populus xylem.
AB  - Recalcitrance of lignocellulosic biomass to sugar release is a central issue in
      the production of biofuel as an economically viable energy source. Among all
      contributing factors, variations in lignin content and its syringyl-guaiacyl
      monomer composition have been directly linked with the yield of fermentable
      sugars. While recent advances in genomics and metabolite profiling have
      significantly broadened our understanding of lignin biosynthesis, its regulation
      at the pathway level is yet poorly understood. During the past decade,
      computational and mathematical methods of systems biology have become effective
      tools for deciphering the structure and regulation of complex metabolic networks.
      As increasing amounts of data from various organizational levels are being
      published, the application of these methods to studying lignin biosynthesis
      appears to be very beneficial for the future development of genetically
      engineered crops with reduced recalcitrance. Here, we use techniques from flux
      balance analysis and nonlinear dynamic modeling to construct a mathematical model
      of monolignol biosynthesis in Populus xylem. Various types of experimental data
      from the literature are used to identify the statistically most significant
      parameters and to estimate their values through an ensemble approach. The thus
      generated ensemble of models yields results that are quantitatively consistent
      with several transgenic experiments, including two experiments not used in the
      model construction. Additional model results not only reveal probable substrate
      saturation at steps leading to the synthesis of sinapyl alcohol, but also suggest
      that the ratio of syringyl to guaiacyl monomers might not be affected by genetic
      modulations prior to the reactions involving coniferaldehyde. This latter model
      prediction is directly supported by data from transgenic experiments. Finally, we
      demonstrate the applicability of the model in metabolic engineering, where the
      pathway is to be optimized toward a higher yield of xylose through modification
      of the relative amounts of the two major monolignols. The results generated by
      our preliminary model of in vivo lignin biosynthesis are encouraging and
      demonstrate that mathematical modeling is poised to become an effective and
      predictive complement to traditional biotechnological and transgenic approaches,
      not just in microorganisms but also in plants.

PMID- 20816868
TI  - Designing dynamical output feedback controllers for store-operated Ca2+ entry.
AB  - Store-operated calcium entry (SOCE) has been proposed as the main process
      controlling Ca2+ entry in non-excitable cells. Although recent breakthroughs in
      experimental studies of SOCE have been made, its mathematical modeling has not
      been developed. In the present work, SOCE is viewed as a feedback control system
      subject to an extracellular agonist disturbance and an extracellular calcium
      input. We then design a dynamic output feedback controller to reject the
      disturbance and track Ca2+ resting levels in the cytosol and the endoplasmic
      reticulum (ER). The constructed feedback control system is validated by published
      experimental data and its global asymptotic stability is proved by using the
      LaSalle's invariance principle. We then simulate the dynamic responses of STIM1
      and Orai1, two major components in the operation of the store-operated channels,
      to the depletion of Ca2+ in the ER with thapsigargin, which show that: (1) Upon
      the depletion of Ca2+ in the ER, the concentrations of activated STIM1 and STIM1
      Orai1 cluster are elevated gradually, indicating that STIM1 is accumulating in
      the ER-PM junctions and that the cytosolic portion of the active STIM1 is binding
      to Orai1 and driving the opening of CRAC channels for Ca2+ entry; (2) after the
      extracellular Ca2+ addition, the concentrations of both STIM1 and STIM1-Orai1
      cluster decrease but still much higher than the original levels. We also simulate
      the system responses to the agonist disturbance, which show that, when a sequence
      of periodic agonist pulses is applied, the system returns to its equilibrium
      after each pulse. This indicates that the designed feedback controller can reject
      the disturbance and track the equilibrium.

PMID- 20816869
TI  - Dual excitation wavelength epifluorescence imaging of transmural
      electrophysiological properties in intact hearts.
AB  - BACKGROUND: Epifluorescence imaging using voltage-sensitive dyes has provided
      unique insights into cardiac electrical activity and arrhythmias. However,
      conventional dyes use blue-green excitation light, which has limited depth
      penetration. OBJECTIVE: The aim of this study was to demonstrate that combining a
      short and a long excitation wavelength using near-infrared (NIR) dyes allows for
      epifluorescence imaging of transmural electrophysiological properties in intact
      hearts. METHODS: Epifluorescence imaging was performed in rat hearts (N = 11)
      using DI-4-ANEPPS and the NIR dye DI-4-ANBDQBS. Activation and action potential
      duration (APD) patterns were investigated at 2 excitation wavelengths (530 and
      660 nm) after epicardial stimulation at various cycle lengths (160 to 70 ms).
      RESULTS: Optical action potential upstrokes acquired with 660-nm excitation of DI
      4-ANBDQBS were significantly longer than upstrokes obtained with 530-nm
      excitation of DI-4-ANEPPS (P < .001). Comparison of activation maps showed
      counterclockwise rotation of isochrones consistent with a transmural rotation of
      myofibers. Pronounced APD modulation by the activation sequence was observed at
      both excitation wavelengths. Significantly prolonged APDs (P = .016) and steeper
      APD restitution curves were found with DI-4-ANBDQBS (660-nm excitation) when
      compared with DI-4-ANEPPS (530-nm excitation). Dual excitation wavelength
      experiments using solely DI-4-ANBDQBS yielded similar results. Monophasic action
      potential recordings showed prolonged APD and steeper APD restitution curves in
      the endocardium, indicating that 660-nm excitation provides a significant
      endocardial contribution to the signal. Three-dimensional computer simulations
      confirmed our findings. CONCLUSION: Dual excitation wavelength epifluorescence
      allows detecting transmural heterogeneity in intact hearts. It therefore has the
      potential to become an important tool in experimental cardiac electrophysiology.

PMID- 20816870
TI  - Prolongation of local ventriculoatrial conduction during left lateral accessory
      pathway ablation: what is the mechanism?

PMID- 20816871
TI  - Clinicians' views regarding deactivation of cardiovascular implantable electronic
      devices in seriously ill patients.

PMID- 20816872
TI  - Implantable cardioverter defibrillator therapy for congenital long QT syndrome: a
      single-center experience.
AB  - BACKGROUND: Long QT syndrome's (LQTS) marked heterogeneity necessitates both
      evidence-based and individualized therapeutic approaches. OBJECTIVE: This study
      sought to analyze a single LQTS specialty center's experience regarding the
      relationship between risk factors and appropriate ventricular fibrillation (VF)
      terminating therapies among LQTS patients treated with an implantable
      cardioverter-defibrillator (ICD). METHODS: An internal review board-approved,
      retrospective analysis of the electronic medical records of 459 patients with
      genetically confirmed LQTS including the 51 patients (14 LQT1, 22 LQT2, and 15
      LQT3) who received an ICD from 2000 to 2010 was performed. RESULTS: Twelve
      patients (24%, 4 LQT1, 8 LQT2) experienced an appropriate, VF-terminating therapy
      with an average follow-up of 7.3 years, including 7 of 17 LQT2 female patients
      but none of the 15 LQT3 patients. Conversely, 15 (29%) patients (8 LQT3) have
      experienced an inappropriate shock. Secondary prevention indications (P = .008),
      non-LQT3 genotype (P = .02), QTc >= 500 ms (P = .0008), documented syncope (P =
      .05), documented torsades de pointes (P = .003), and a negative family history (P
      = .0001) were most predictive of an appropriate therapy. Importantly, no LQT
      related deaths have occurred among the 408 non-ICD-treated patients. CONCLUSION:
      The vast majority of LQTS patients can be treated effectively without an ICD.
      Potentially life-saving therapies were rendered at a 5% to 6% per year rate among
      those selected for ICD therapy; similar inappropriate shock frequencies were also
      noted. Secondary prevention, genotype, and QTc predicted those most likely to
      receive appropriate therapy. Although the ICD implant frequency is greatest among
      LQT3 patients, the greatest "save" rate has occurred among LQT2 women, who were
      assessed to be at high risk.

PMID- 20816873
TI  - Beat-to-beat three-dimensional ECG variability predicts ventricular arrhythmia in
      ICD recipients.
AB  - BACKGROUND: Methodological difficulties associated with QT measurements prompt
      the search for new electrocardiographic markers of repolarization heterogeneity.
      OBJECTIVE: We hypothesized that beat-to-beat 3-dimensional vectorcardiogram
      variability predicts ventricular arrhythmia (VA) in patients with structural
      heart disease, left ventricular systolic dysfunction, and implanted implantable
      cardioverter-defibrillators (ICDs). METHODS: Baseline orthogonal
      electrocardiograms were recorded in 414 patients with structural heart disease
      (mean age 59.4 +/- 12.0; 280 white [68%] and 134 black [32%]) at rest before
      implantation of ICD for primary prevention of sudden cardiac death. R and T peaks
      of 30 consecutive sinus beats were plotted in 3 dimensions to form an R peaks
      cloud and a T peaks cloud. The volume of the peaks cloud was calculated as the
      volume within the convex hull. Patients were followed up for at least 6 months;
      sustained VA with appropriate ICD therapies served as an end point. RESULTS:
      During a mean follow-up time of 18.4 +/- 12.5 months, 61 of the 414 patients
      (14.73% or 9.6% per person-year of follow-up) experienced sustained VA with
      appropriate ICD therapies: 41 of them were white and 20 were black. In the
      multivariate Cox model that included inducibility of VA and use of beta-blockers,
      the highest tertile of T/R peaks cloud volume ratio significantly predicted VA
      (hazard ratio 1.68, 95% confidence interval 1.01 to 2.80; P = .046) in all
      patients. T peaks cloud volume and T/R peaks cloud volume ratio were
      significantly smaller in black subjects (median 0.09 [interquartile range 0.04 to
      0.15] vs. median 0.11 [interquartile range 0.06 to 0.22], P = .002). CONCLUSION:
      A relatively large T peaks cloud volume is associated with increased risk of VA
      in patients with structural heart disease and systolic dysfunction.

PMID- 20816874
TI  - Highly stable, ligand-clustered "patchy" micelle nanocarriers for systemic tumor
      targeting.
AB  - A novel linear-dendritic block copolymer has been synthesized and evaluated for
      targeted delivery. The use of the dendron as the micellar exterior block in this
      architecture allows the presentation of a relatively small quantity of ligands in
      clusters for enhanced targeting, thus maintaining a long circulation time of
      these "patchy" micelles. The polypeptide linear hydrophobic block drives
      formation of micelles that carry core-loaded drugs, and their unique design gives
      them extremely high stability in vivo. We have found that these systems lead to
      extended time periods of increased accumulation in the tumor (up to 5 days)
      compared with nontargeted vehicles. We also demonstrate a fourfold increase in
      efficacy of paclitaxel when delivered in the targeted nanoparticle systems, while
      significantly decreasing in vivo toxicity of the chemotherapy treatment. FROM THE
      CLINICAL EDITOR: A micellar vehicle using dendrons as the exterior block in
      combination with a polypeptide hydrophobic block was shown to incorporate and
      deliver paclitaxel to xenograft tumors with a four-fold increase in efficacy and
      reduced toxicity.

PMID- 20816875
TI  - The binding sites for benztropines and dopamine in the dopamine transporter
      overlap.
AB  - Analogs of benztropines (BZTs) are potent inhibitors of the dopamine transporter
      (DAT) but are less effective than cocaine as behavioral stimulants. As a result,
      there have been efforts to evaluate these compounds as leads for potential
      medication for cocaine addiction. Here we use computational modeling together
      with site-directed mutagenesis to characterize the binding site for BZTs in DAT.
      Docking into molecular models based on the structure of the bacterial homolog
      LeuT supported a BZT binding site that overlaps with the substrate-binding
      pocket. In agreement, mutations of residues within the pocket, including(2)
      Val152(3.46) to Ala or Ile, Ser422(8.60) to Ala and Asn157(3.51) to Cys or Ala,
      resulted in decreased affinity for BZT and the analog JHW007, as assessed in
      [(3)H]dopamine uptake inhibition assays and/or [(3)H]CFT competition binding
      assay. A putative polar interaction of one of the phenyl ring fluorine
      substituents in JHW007 with Asn157(3.51) was used as a criterion for determining
      likely binding poses and establish a structural context for the mutagenesis
      findings. The analysis positioned the other fluorine-substituted phenyl ring of
      JHW007 in close proximity to Ala479(10.51)/Ala480(10.52) in transmembrane segment
      (TM) 10. The lack of such an interaction for BZT led to a more tilted
      orientation, as compared to JHW007, bringing one of the phenyl rings even closer
      to Ala479(10.51)/Ala480(10.52). Mutation of Ala479(10.51) and Ala480(10.52) to
      valines supported these predictions with a larger decrease in the affinity for
      BZT than for JHW007. Summarized, our data suggest that BZTs display a classical
      competitive binding mode with binding sites overlapping those of cocaine and
      dopamine.

PMID- 20816876
TI  - Somatic mutations of mitochondrial DNA in aging and cancer progression.
AB  - Mitochondria are intracellular organelles responsible for generating ATP through
      respiration and oxidative phosphorylation (OXPHOS), producing reactive oxygen
      species, and initiating and executing apoptosis. Mitochondrial dysfunction has
      been observed to be an important hallmark of aging and cancer. Because
      mitochondrial DNA (mtDNA) is important in maintaining functionally competent
      organelles, accumulation of mtDNA mutations can affect energy production,
      oxidative stress, and cell survival, which may contribute to aging and/or
      carcinogenesis. This review outlines a variety of somatic mtDNA mutations
      identified in aging tissues and human cancers, as well as recent advances in
      understanding the causal role of mtDNA mutations in the aging process and cancer
      progression. Mitochondrial dysfunction elicited by somatic mutations in mtDNA
      could induce apoptosis in aging cells and some cancer cells with severe mtDNA
      mutations. In addition, it could activate mitochondria-to-nucleus retrograde
      signaling to modulate the expression of nuclear genes involved in a metabolic
      shift from OXPHOS to glycolysis, facilitate cells to adapt to altered
      environments and develop resistance to chemotherapeutic agents, or promote
      metastatic properties of cancer cells. These findings suggest that accumulation
      of somatic mtDNA mutations is not only an important contributor to human aging
      but also plays a critical role in cancer progression.

PMID- 20816877
TI  - Experience-dependent plasticity of white-matter microstructure extends into old
      age.
AB  - Experience-dependent alterations in the human brain's white-matter microstructure
      occur in early adulthood, but it is unknown whether such plasticity extends
      throughout life. We used cognitive training, diffusion-tensor imaging (DTI), and
      structural MRI to investigate plasticity of the white-matter tracts that connect
      the left and right hemisphere of the frontal lobes. Over a period of about 180
      days, 20 younger adults and 12 older adults trained for a total of one hundred
      and one 1-h sessions on a set of three working memory, three episodic memory, and
      six perceptual speed tasks. Control groups were assessed at pre- and post-test.
      Training affected several DTI metrics and increased the area of the anterior part
      of the corpus callosum. These alterations were of similar magnitude in younger
      and older adults. The findings indicate that experience-dependent plasticity of
      white-matter microstructure extends into old age and that disruptions of
      structural interhemispheric connectivity in old age, which are pronounced in
      aging, are modifiable by experience and amenable to treatment.

PMID- 20816878
TI  - Different degrees of structural order in distinct regions of the transcriptional
      repressor HES-1.
AB  - HES-1 is a transcriptional repressor of the basic helix-loop-helix (bHLH) family
      and one of the main downstream effectors in Notch signaling. Its domain
      architecture is composed of a bHLH region, an Orange domain, and a poorly
      characterized C-terminal half. We show that different degrees of structural order
      are present in the different regions of HES-1. The isolated bHLH domain is only
      marginally stable in solution, and partially folds upon dimerization. Binding to
      DNA promotes folding, stabilization, and protection from proteolysis of the bHLH
      domain. The Orange domain, on the contrary, is well folded in all conditions,
      forms stable dimers, and greatly increases protein resistance to thermal
      denaturation. The isolated proline-rich C-terminal region is mainly disordered in
      solution, and remains unstructured also in the full length protein. Measurements
      of binding constants show that HES-1 recognizes dsDNA synthetic oligonucleotides
      corresponding to several functional DNA targets with high affinity, but with
      relatively little specificity. We propose that order/disorder transitions in the
      different domains are associated not only with binding to DNA, but also with
      protein homo- and hetero-dimerization.

PMID- 20816879
TI  - Progesterone rapidly recruits female-typical opioid-induced hyperalgesic
      mechanisms.
AB  - Continuous morphine treatment can paradoxically increase nociception (i.e.
      hyperalgesia) in male and female mice, but sex differences have been reported.
      Here, we studied progesterone modulation of these differences by assessing
      nociception on the tail-withdrawal test in male and female mice rendered
      hyperalgesic during continuous infusion of two different morphine doses (1.6 and
      40.0mg/kg/24h). Although the lower morphine infusion dose increased nociception
      in both sexes by infusion Day 4, this hyperalgesia dissipated by Day 6 in males
      and ovariectomized females, but not gonadally intact females. A single
      subcutaneous progesterone (0.0016mg/kg) injection to males and ovariectomized
      females on Day 6 caused hyperalgesia to recur within 30min and to persist for a
      minimum of 120min. The larger morphine infusion dose also increased nociception
      in both sexes on Days 4 and 6. However, the NMDA receptor antagonist MK-801
      (0.05mg/kg) reversed hyperalgesia in males and ovariectomized females but not
      gonadally intact females on infusion Day 6. Subcutaneous progesterone
      (0.0016mg/kg) injection inhibited this reversal in male and ovariectomized female
      mice but had no effect on nociception in saline-infused mice of either sex. These
      data confirm our previous findings that male and female mice utilize distinct
      hyperalgesic mechanisms, and show for the first time that a single progesterone
      bolus dose can recruit female-typical hyperalgesia in ovariectomized females and
      males.

PMID- 20816880
TI  - Protein profiling identified dissociations between growth hormone-mediated
      longitudinal growth and bone mineralization in short prepubertal children.
AB  - Growth hormone (GH) promotes longitudinal growth and bone mineralization. In this
      study, a proteomic approach was used to analyze the association between serum
      protein expression pattern and height-adjusted bone mineralization in short
      prepubertal children receiving GH treatment. Patterns of protein expression were
      compared with those associated with longitudinal bone growth. Specific protein
      expression patterns associated with changes in height-adjusted bone
      mineralization in response to GH treatment were identified. Out of the 37 peaks
      found in significant regression models, 27 were uniquely present in models
      correlated with changes in bone mineralization and 7 peaks were uniquely present
      in models correlated with changes in height. The peaks identified corresponded to
      apolipoproteins, transthyretin, serum amyloid A4 and hemoglobin beta. We conclude
      that a proteomic approach could be used to identify specific protein expression
      patterns associated with bone mineralization in response to GH treatment and that
      height-adjusted bone mineralization and longitudinal bone growth are regulated
      partly by the same and partly by different mechanisms. Protein isoforms with
      different post-translational modifications might be of importance in the
      regulation of these processes. However, further validation is needed to assess
      the clinical significance of the results.

PMID- 20816882
TI  - The early phase of a bacterial insertion sequence infection.
AB  - Bacterial insertion sequences are the simplest form of autonomous mobile DNA. It
      is unknown whether they need to have beneficial effects to infect and persist in
      bacterial populations, or whether horizontal gene transfer suffices for their
      persistence. We address this question by using branching process models to
      investigate the critical, early phase of an insertion sequence infection. We find
      that the probability of a successful infection is low and depends linearly on the
      difference between the rate of horizontal gene transfer and the fitness cost of
      the insertion sequences. Our models show that the median time to extinction of an
      insertion sequence that dies out is very short, while the median time for a
      successful infection to reach a modest population size is very long. We conclude
      that horizontal gene transfer is strong enough to allow the persistence of
      insertion sequences, although infection is an erratic and slow process.

PMID- 20816883
TI  - Preferential induction of the AhR gene battery in HepaRG cells after a single or
      repeated exposure to heterocyclic aromatic amines.
AB  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8
      dimethylimidazo[4,5-f]quinoxaline (MeIQx) are two of the most common heterocyclic
      aromatic amines (HAA) produced during cooking of meat, fish and poultry. Both HAA
      produce different tumor profiles in rodents and are suspected to be carcinogenic
      in humans. In order to better understand the molecular basis of HAA toxicity, we
      have analyzed gene expression profiles in the metabolically competent human
      HepaRG cells using pangenomic oligonucleotide microarrays, after either a single
      (24-h) or a repeated (28-day) exposure to 10 MUM PhIP or MeIQx. The most
      responsive genes to both HAA were downstream targets of the arylhydrocarbon
      receptor (AhR): CYP1A1 and CYP1A2 after both time points and CYP1B1 and ALDH3A1
      after 28 days. Accordingly, CYP1A1/1A2 induction in HAA-treated HepaRG cells was
      prevented by chemical inhibition or small interference RNA-mediated down
      regulation of the AhR. Consistently, HAA induced activity of the CYP1A1 promoter,
      which contains a consensus AhR-related xenobiotic-responsive element (XRE). In
      addition, several other genes exhibited both time-dependent and compound-specific
      expression changes with, however, a smaller magnitude than previously reported
      for the prototypical AhR target genes. These changes concerned genes mainly
      related to cell growth and proliferation, apoptosis, and cancer. In conclusion,
      these results identify the AhR gene battery as the preferential target of PhIP
      and MeIQx in HepaRG cells and further support the hypothesis that intake of HAA
      in diet might increase human cancer risk.

PMID- 20816884
TI  - Xanthine oxidase-derived reactive oxygen species mediate 4-oxo-2-nonenal-induced
      hepatocyte cell death.
AB  - Among the aldehydes derived from lipid peroxidation, there have been several
      reports concerning the toxicity of 4-hydroxy-2-nonenal (4-HNE), whereas little
      information is available about 4-oxo-2-nonenal (4-ONE). In the present study, we
      examined the effects of 4-HNE and 4-ONE on the cell viability of primary rat
      hepatocyte cultures. At concentrations of 5, 10, and 20 MUM, 4-HNE had no
      significant effect on the cell viability of primary rat hepatocytes cultures,
      whereas 4-ONE potently decreased the cell viability in a dose-dependent manner (5
      20 MUM, 23-69% inhibition). The TUNEL assay showed that 4-ONE causes apoptosis in
      the cells. 4-ONE also increased 2',7'-dichlorofluorescein-fluorescence intensity
      from 2',7'-dichlorodihydrofluorescein, an indicator of reactive oxygen species
      (ROS) generation. Allopurinol, a xanthine oxidase (XO) inhibitor, diminished the
      4-ONE-induced increase in the 2',7'-dichlorofluorescein-fluorescence intensity
      and the decrease in viability, indicating the role of XO in mediating 4-ONE
      induced cell death. These observations suggest that 4-ONE has the potential to
      induce liver cell death via XO-derived ROS generation.

PMID- 20816885
TI  - Enhancement of the predicted drug hepatotoxicity in gel entrapped hepatocytes
      within polysulfone-g-poly (ethylene glycol) modified hollow fiber.
AB  - Collagen gel-based 3D cultures of hepatocytes have been proposed for evaluation
      of drug hepatotoxicity because of their more reliability than traditional
      monolayer culture. The collagen gel entrapment of hepatocytes in hollow fibers
      has been proven to well reflect the drug hepatotoxicity in vivo but was limited
      by adsorption of hydrophobic drugs onto hollow fibers. This study aimed to
      investigate the impact of hollow fibers on hepatocyte performance and drug
      hepatotoxicity. Polysulfone-g-poly (ethylene glycol) (PSf-g-PEG) hollow fiber was
      fabricated and applied for the first time to suppress the drug adsorption. Then,
      the impact of hollow fibers was evaluated by detecting the hepatotoxicity of
      eight selected drugs to gel entrapped hepatocytes within PSf and PSf-g-PEG hollow
      fibers, or without hollow fibers. The hepatocytes in PSf-g-PEG hollow fiber
      showed the highest sensitivity to drug hepatotoxicity, while those in PSf hollow
      fiber and cylindrical gel without hollow fiber underestimated the hepatotoxicity
      due to either drug adsorption or low hepatic functions. Therefore, the 3D culture
      of gel entrapped hepatocytes within PSf-g-PEG hollow fiber would be a promising
      tool for investigation of drug hepatotoxicity in vitro.

PMID- 20816886
TI  - Comparative analysis of newborn and adult Bothrops jararaca snake venoms.
AB  - Different clinical manifestations have been reported to occur in patients bitten
      by newborn and adult Bothrops jararaca snakes. Herein, we studied the chemical
      composition and biological activities of B. jararaca venoms and their
      immunoneutralization by commercial antivenin at these ontogenetic stages.
      Important differences in protein profiles were noticed both in SDS-PAGE and two
      dimensional electrophoresis. Newborn venom showed lower proteolytic activity on
      collagen and fibrinogen, diminished hemorrhagic activity in mouse skin and hind
      paws, and lower edematogenic, ADPase and 5'-nucleotidase activities. However,
      newborn snake venom showed higher l-amino oxidase, hyaluronidase, platelet
      aggregating, procoagulant and protein C activating activities. The adult venom is
      more lethal to mice than the newborn venom. In vitro and in vivo
      immunoneutralization tests showed that commercial Bothrops sp antivenin is less
      effective at neutralizing newborn venoms. These findings indicate remarkable
      differences in biological activities of B. jararaca venom over its development.
      We suggest that not only venom from adult specimens, but also from specimens at
      other ontogenetic stages should be included in the venom pool used for raising
      antibodies. Thus, Bothrops antivenin can efficaciously neutralize proteins
      lacking in the adult venom pool, especially those that promote more intense
      hemostatic disturbances in victims of newborn snakes.

PMID- 20816887
TI  - Interactions between gaze-centered and allocentric representations of reach
      target location in the presence of spatial updating.
AB  - Numerous studies have investigated the phenomenon of egocentric spatial updating
      in gaze-centered coordinates, and some have studied the use of allocentric cues
      in visually-guided movement, but it is not known how these two mechanisms
      interact. Here, we tested whether gaze-centered and allocentric information
      combine at the time of viewing the target, or if the brain waits until the last
      possible moment. To do this, we took advantage of the well-known fact that
      pointing and reaching movements show gaze-centered 'retinal magnification' errors
      (RME) that update across saccades. During gaze fixation, we found that visual
      landmarks, and hence allocentric information, reduces RME for targets in the left
      visual hemifield but not in the right. When a saccade was made between viewing
      and reaching, this landmark-induced reduction in RME only depended on gaze at
      reach, not at encoding. Based on this finding, we argue that egocentric
      allocentric combination occurs after the intervening saccade. This is consistent
      with previous findings in healthy and brain damaged subjects suggesting that the
      brain updates early spatial representations during eye movement and combines them
      at the time of action.

PMID- 20816881
TI  - A survey of computational methods and error rate estimation procedures for
      peptide and protein identification in shotgun proteomics.
AB  - This manuscript provides a comprehensive review of the peptide and protein
      identification process using tandem mass spectrometry (MS/MS) data generated in
      shotgun proteomic experiments. The commonly used methods for assigning peptide
      sequences to MS/MS spectra are critically discussed and compared, from basic
      strategies to advanced multi-stage approaches. A particular attention is paid to
      the problem of false-positive identifications. Existing statistical approaches
      for assessing the significance of peptide to spectrum matches are surveyed,
      ranging from single-spectrum approaches such as expectation values to global
      error rate estimation procedures such as false discovery rates and posterior
      probabilities. The importance of using auxiliary discriminant information (mass
      accuracy, peptide separation coordinates, digestion properties, and etc.) is
      discussed, and advanced computational approaches for joint modeling of multiple
      sources of information are presented. This review also includes a detailed
      analysis of the issues affecting the interpretation of data at the protein level,
      including the amplification of error rates when going from peptide to protein
      level, and the ambiguities in inferring the identifies of sample proteins in the
      presence of shared peptides. Commonly used methods for computing protein-level
      confidence scores are discussed in detail. The review concludes with a discussion
      of several outstanding computational issues.

PMID- 20816888
TI  - Interaction of glutathione depletion and psychotropic drug treatment in prepulse
      inhibition in rats and mice.
AB  - Oxidative stress has been implicated in several psychiatric illnesses, including
      schizophrenia. Glutathione is the brain's primary antioxidant and decreased
      levels of brain glutathione are reported in schizophrenia. Prepulse inhibition
      (PPI) is a measure of sensory gating, and PPI is reduced in schizophrenia. This
      study aimed to investigate the effects of brain glutathione depletion on PPI
      regulation. Rats and mice were treated with the glutathione-depleting agent, 2
      cyclohexene-1-one (CHX), and tested for baseline PPI and its disruption by
      treatment with amphetamine and MK-801. Treatment with CHX caused significant
      depletion of GSH in frontal cortex and striatum of rats and mice. Baseline PPI
      and startle were not altered. However, the disruption of PPI after treatment with
      amphetamine was absent in CHX-treated rats. In contrast, the effect of MK-801 was
      not altered by CHX-treatment, nor was there any effect of CHX treatment in mice.
      These data show an interaction of glutathione depletion with the effects of
      amphetamine treatment on PPI in rats. This effect could reflect loss of
      plasticity in PPI regulation caused by the additive effects of CHX-induced
      glutathione depletion and additional oxidative stress caused by amphetamine
      induced dopamine release. The significance of these results for schizophrenia is
      discussed.

PMID- 20816889
TI  - Levo-tetrahydropalmatine attenuates cocaine self-administration under a
      progressive-ratio schedule and cocaine discrimination in rats.
AB  - Levo-tetrahydropalmatine (l-THP) is an alkaloid found in many traditional Chinese
      herbal preparations and has a unique pharmacological profile that includes
      dopamine receptor antagonism. Previously we demonstrated that l-THP attenuates
      fixed-ratio (FR) cocaine self-administration (SA) and cocaine-induced
      reinstatement in rats at doses that do not alter food-reinforced responding. This
      study examined the effects of l-THP on cocaine and food SA under progressive
      ratio (PR) schedules of reinforcement and the discriminative stimulus effects of
      cocaine. In adult male Sprague-Dawley rats self-administering cocaine (0.5 or
      1.0mg/kg/inf), l-THP significantly reduced breaking points at the 1.875, 3.75 and
      7.5mg/kg doses. l-THP also reduced the breaking point and response rate for PR SA
      of sucrose-sweetened food pellets, although the decrease was significant only at
      the 7.5mg/kg l-THP dose. In rats trained to discriminate cocaine (10mg/kg, ip)
      from saline, l-THP (1.875, 3.75 and 7.5mg/kg) produced a rightward shift in the
      dose-response curve for cocaine generalization. During generalization testing, l
      THP reduced response rate, but only at the 7.5mg/kg dose. l-THP also prevented
      substitution of the dopamine D2/D3 receptor agonist, (+/-) 7-OH-DPAT, for cocaine
      suggesting a potential role for antagonism of D2 and/or D3 receptors in the
      effects of l-THP. These data further demonstrate that l-THP attenuates the
      reinforcing and subjective effects of cocaine at doses that do not produce marked
      motor effects and provide additional evidence that l-THP may have utility for the
      management of cocaine addiction.

PMID- 20816890
TI  - Progesterone reduces the inhibitory effect of a serotonin 1B receptor agonist on
      lordosis behavior.
AB  - Ovariectomized Fischer inbred rats were hormonally primed with 10MUg estradiol
      benzoate and sesame seed oil (EO rats) or with estradiol benzoate and 500MUg
      progesterone (EP rats). Four to six hours after progesterone or oil, rats were
      pretested for sexual behavior and then infused bilaterally into the ventromedial
      nucleus of the hypothalamus with 0, 50, 100 or 200ng of the 5-HT(1B) receptor
      agonist, 1,4-dihydro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-5H-pyrrol[3,2-bi]pyridin
      5-one-dihydrochloride (CP 93129). Sexual receptivity was monitored by the
      lordosis to mount (L/M) ratio. EO rats showed a transient decline in lordosis
      behavior following infusion with the saline vehicle and this was amplified by CP
      93129. There were no effects of any infusion in EP rats. These findings are
      discussed in terms of the possible stress effect of the intracranial infusion in
      EO rats and their implications for a role of 5-HT(1B) receptors in the response
      to a mild stress.

PMID- 20816892
TI  - Litopenaeus vannamei tumor necrosis factor receptor-associated factor 6 (TRAF6)
      responds to Vibrio alginolyticus and white spot syndrome virus (WSSV) infection
      and activates antimicrobial peptide genes.
AB  - Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is a key
      signaling adaptor protein not only for the TNFR superfamily but also for the
      Interleukin-1 receptor/Toll-like receptor (IL-1/TLR) superfamily. To investigate
      TRAF6 function in invertebrate innate immune responses, Litopenaeus vannamei
      TRAF6 (LvTRAF6) was identified and characterized. The full-length cDNA of LvTRAF6
      is 2823bp long, with an open reading frame (ORF) encoding a putative protein of
      594 amino acids, including a RING-type Zinc finger, two TRAF-type Zinc fingers, a
      coiled-coil region, and a meprin and TRAF homology (MATH) domain. The overall
      amino acid sequence identity between LvTRAF6 and other known TRAF6s is 22.2
      33.3%. Dual luciferase reporter assays in Drosophila S2 cells revealed that
      LvTRAF6 could activate the promoters of antimicrobial peptide genes (AMPs),
      including Drosophila Attacin A and Drosomycin, and shrimp Penaeidins. Real-time
      quantitative PCR (qPCR) indicated that LvTRAF6 was constitutively expressed in
      various tissues of L. vannamei. After Vibrio alginolyticus and white spot
      syndrome virus (WSSV) challenge, LvTRAF6 was down-regulated, though with
      different expression patterns in the intestine compared to other tissues. After
      WSSV challenge, LvTRAF6 was up-regulated 2.7- and 2.3-fold over the control at 3h
      in gills and hepatopancreas, respectively. These results indicated that LvTRAF6
      may play a crucial role in antibacterial and antiviral responses via regulation
      of AMP gene expression.

PMID- 20816891
TI  - Tobacco dependence, the insular cortex and the hypocretin connection.
AB  - Tobacco use is a major cause of disease and premature death in the United States.
      Nicotine is considered the key component of tobacco responsible for addiction in
      human smokers. Accumulating evidence supports an important role for the
      hypocretin (orexin) neuropeptide system in regulating the reinforcing properties
      of most major drugs of abuse, including nicotine. Here, data showing that
      nicotine activates hypocretin-producing neurons in the lateral hypothalamus, and
      that disruption of hypocretin transmission decreases nicotine self-administration
      behavior in rats will be reviewed. Recent findings suggesting that plasma
      hypocretin levels may be related to the magnitude of cigarette craving in
      abstinent smokers will be discussed. Finally, the data suggesting that hypocretin
      transmission in the insular cortex may play an important role in regulating
      nicotine self-administration behavior in rats will be reviewed. This latter
      finding may provide mechanistic insight into the apparent disruption of tobacco
      addiction reported in human smokers with stroke-associated damage to the insular
      cortex.

PMID- 20816893
TI  - Possible role of phosphatidylserine-hemocyanin interaction in the innate immune
      response of Limulus polyphemus.
AB  - Phenoloxidase enzymes and the associated pro-phenoloxidase activation cascade
      play an essential role in the immune response of arthropods. Phenoloxidase
      activity can be elicited in the oxygen carrier, hemocyanin, by the addition of
      the artificial inducer, SDS. There is some evidence to support hemocyanin acting
      as a phenoloxidase in vivo; however, the identity of natural activators remains
      unclear. This study explores the role of the phospholipid, phosphatidylserine, as
      a possible natural activator of hemocyanin-derived phenoloxidase activity.
      Characterisation of the structural changes associated with activation of
      hemocyanin-derived phenoloxidase suggests that phosphatidylserine induces similar
      conformational changes to those caused by the artificial inducer, SDS. We propose
      that anionic phospholipids, in particular phosphatidylserine, may act as natural
      activators of hemocyanin-derived phenoloxidase.

PMID- 20816894
TI  - An ancient molecule with novel function: Alanine aminotransferase as a
      lipopolysaccharide binding protein with bacteriocidal activity.
AB  - Alanine aminotransaminase (ALT) has been identified from bacteria to plants to
      animals including humans. The increase in serum ALT is regarded as an index for
      clinical diagnosis of liver function in humans. However, ALT elevation is also
      reported in non-liver injury conditions and in apparently healthy people,
      suggesting it may play a fundamental role physiologically. Herein we isolated an
      alt homolog, Amphialt, from Branchiostoma japonicus, an intermediatary species
      from invertebrates to vertebrates, which encoded a polypeptide of 500 amino acids
      with more than 62 and 52% sequence identity to vertebrate and invertebrate ALT
      isoenzymes, respectively. It was constitutively expressed in many tissues
      including the hepatic caecum, the precursor of liver, and its expression in the
      caecum was significantly up-regulated by challenge with lipopolysaccharides
      (LPS). Strikingly, recombinant AmphiALT, with a specific activity of 0.114+/
      0.02U/mg, was capable of specifically binding to the Gram-negative bacteria
      Escherichia coli and Aeromonas hydrophila and to their conserved molecule LPS, as
      well as inhibiting the growth of E. coli and causing its lysis. In contrast,
      AmphiALT did not bind to the Gram-positive bacteria Staphyloccocus aureus and
      Bacillus subtilis as well as their conserved molecule LTA. In addition, a high
      homology noted between amphioxus and mammalian ALT sequences suggested a
      functional conservation of ALT evolutionarily, hinting at the clue that mammalian
      ALT may also play an antibacterial role similar to that of AmphiALT. Taken
      together, it is proposed that AmphiALT is an immune-relevant molecule capable of
      identifying LPS and causing damage to Gram-negative bacteria like E. coli and A.
      hydrophila. It also bolsters the notion that the hepatic caecum of amphioxus is
      the precursor of vertebrate liver, acting as a major tissue in acute phase
      response.

PMID- 20816895
TI  - Cholera toxin inhibits HIV-1 replication in human colorectal epithelial HT-29
      cells through adenylate cyclase activation.
AB  - Mixed feeding, combining breast milk and nonhuman milk and/or solid food, is a
      common practice in developing countries that increases the risk of vertical HIV-1
      transmission. It also enhances the risk of infection by waterborne microorganisms
      such as Vibrio cholerae, a diarrhoea-causing pathogen that frequently infects
      children below 18 months of age. Although both HIV-1 and V. cholerae affect young
      children and target intestinal epithelial cells, no information is currently
      available on possible interactions between these two pathogens. In this study, we
      show for the first time that cholera toxin (CTx), at a concentration as low as
      100 pg/ml, inhibits HIV-1 infection of HT-29, a human colorectal epithelial cell
      line. The CTx-mediated inhibitory effect does not result from a down-regulation
      of receptor/co-receptor expression or a modulation of viral transcription.
      Nevertheless, additional experiments indicate that a yet to be identified early
      step in the virus life cycle is targeted by CTx since the enterotoxin similarly
      reduces infection of HT-29 cells with AMLV-I, HTLV-I and HIV-1 pseudotyped
      viruses while exerting no effect on infection with VSV-G pseudotypes.
      Furthermore, our results indicate that the CTx-dependent suppression is not due
      to the cholera toxin subunit B but linked instead to the action of cholera toxin
      subunit A (CTA). Altogether our data indicate that the CTA subunit of CTx is
      negatively affecting an early event in HIV-1 replication in human colon cancer HT
      29 cells.

PMID- 20816896
TI  - Inhibition of nuclear factor-kappaB impairs reconsolidation of morphine reward
      memory in rats.
AB  - Drug addiction is a process associated with synaptic plasticity in which a drug
      of abuse affects the midbrain limbic system. Previous studies have indicated that
      drug abuse can be inhibited by disrupting the reconsolidation of a drug-related
      memory. Nuclear factor-kappaB (NF-kappaB) plays an important role in modulating
      different stages of memory, including reconsolidation, but its role in the
      reconsolidation of a reward memory has not been investigated. The aim of the
      present study was to examine the role of NF-kappaB in drug-related memory
      reconsolidation. We found that rats acquired morphine-induced conditioned place
      preference, which was inhibited by the NF-kappaB inhibitor SN50 administered
      after reexposure to a previously morphine-paired chamber (i.e., a memory
      retrieval process). The disruptive effect of SN50 on reward memory
      reconsolidation was reversed by systemic injections of the histone deacetylase
      inhibitor sodium butyrate. These results indicate that SN50 disrupts morphine
      related memory reconsolidation by inhibiting NF-kappaB, and this effect can be
      reversed by inhibiting histone acetylation.

PMID- 20816897
TI  - Two models for weight gain and hyperphagia as side effects of atypical
      antipsychotics in male rats: validation with olanzapine and ziprasidone.
AB  - Body weight gain is one of the most serious side effects associated with clinical
      use of antipsychotics. However, the mechanisms by which antipsychotics induce
      body weight gain are unknown, and no reliable animal models of antipsychotics
      induced weight gain have been established. The present studies were designed to
      establish male rat models of weight gain induced by chronic and acute treatment
      with antipsychotics. Six-week chronic treatment with olanzapine (5, 7.5, and
      10mg/kg/day) in male Sprague-Dawley rats fed a daily diet resembling a human
      macronutrient diet, significantly increased body weight gain and weight of fatty
      tissues. In contrast, ziprasidone (1.25, 2.5, and 5mg/kg/day) administration
      caused no observable adverse effects. We then investigated feeding behavior with
      acute antipsychotic treatment in male rats using an automated food measurement
      apparatus. Rats were allowed restricted access to normal laboratory chow
      (4h/day). With acute olanzapine (0.5, 1, and 2mg/kg, i.p.) treatment in the light
      phase, food intake volume and duration were significantly increased, while
      treatment with ziprasidone (0.3, 1, and 3mg/kg, i.p.) did not increase food
      intake volume or meal time duration. Findings from the present studies showed
      that chronic treatment with olanzapine in male rats induced body weight gain, and
      acute injection induced hyperphagia, suggesting that hyperphagia may be involved
      in the weight gain and obesity-inducing properties of chronically administered
      olanzapine. These animal models may provide useful experimental platforms for
      analysis of the mechanism of hyperphagia and evaluating the potential risk of
      novel antipsychotics to induce weight gain in humans.

PMID- 20816898
TI  - Exploring intermediate phenotypes with EEG: working memory dysfunction in
      schizophrenia.
AB  - This review brings together two strands of investigation in the neuropsychology
      and neurophysiology of schizophrenia that have been particularly productive over
      the last 20 years. We review the literature on working memory deficits,
      particularly in the visual domain, and changes in oscillatory neural activity as
      measured with electroencephalography (EEG) and magnetoencephalography (MEG). We
      argue that recent results suggest a link between these two phenomena, in that
      altered oscillations underlie some of the working memory deficits. We furthermore
      argue that early sensory mechanisms contribute more to working memory (and other)
      deficits than previously thought. The final part of our review suggests links
      between working memory, oscillations, and their alterations in schizophrenia and
      the dopamine, GABA, glutamate and acetylcholine system. These links have already
      resulted in the development of new remediation strategies, which have some
      translational potential.

PMID- 20816900
TI  - Fluoxetine reverts chronic restraint stress-induced depression-like behaviour and
      increases neuropeptide Y and galanin expression in mice.
AB  - Stressful life events and chronic stress are implicated in the development of
      depressive disorder in humans. Neuropeptide Y (NPY) and galanin have been shown
      to modulate the stress response, and exert antidepressant-like effects in
      rodents. To further investigate these neuropeptides in depression-like behaviour,
      NPY and galanin gene expression was studied in brains of mice subjected to
      chronic restraint stress (CRS) and concomitant treatment with the antidepressant
      fluoxetine (FLX). CRS caused a significant increase in depression-like behaviour
      that was associated with increased NPY mRNA levels in the medial amygdala.
      Concomitant FLX treatment reverted depression-like effects of CRS and led to
      significant increases in levels of NPY and galanin mRNA in the dentate gyrus,
      amygdala, and piriform cortex. These findings suggest that effects on NPY and
      galanin gene expression could play a role in the antidepressant effects of FLX.

PMID- 20816899
TI  - The effects of pre-pubertal gonadectomy and binge-like ethanol exposure during
      adolescence on ethanol drinking in adult male and female rats.
AB  - The pubertal surge in gonadal hormones that occurs during adolescence may impact
      the long-term effects of early alcohol exposure and sex differences in drinking
      behavior in adulthood. We investigated this hypothesis by performing sham or
      gonadectomy surgeries in Long-Evans rats around post-natal day (P) 20. From P35
      45, males and females were given saline or 3.0 g/kg ethanol using a binge-like
      model of exposure (8 injections total). As adults (P100), they were trained to
      self-administer ethanol via a sucrose-fading procedure and then given access to
      different unsweetened concentrations (5-20%, w/v) for 5 days/concentration. We
      found that during adolescence, ethanol-induced intoxication was similar in males
      and females that underwent sham surgery. In gonadectomized males and females,
      however, the level of intoxication was greater following the last injection
      compared to the first. During adulthood, females drank more sucrose per body
      weight than males and binge-like exposure to ethanol reduced sucrose consumption
      in both sexes. These effects were not seen in gonadectomized rats. Ethanol
      consumption was higher in saline-exposed females compared to males, with
      gonadectomy reversing this sex difference by increasing consumption in males and
      decreasing it in females. Exposure to ethanol during adolescence augmented
      ethanol consumption in both sexes, but this effect was statistically significant
      only in gonadectomized females. Together, these results support a role for
      gonadal hormones during puberty in the short- and long-term effects of ethanol on
      behavior and in the development of sex differences in consummatory behavior
      during adulthood.

PMID- 20816901
TI  - Vrp1p-Las17p interaction is critical for actin patch polarization but is not
      essential for growth or fluid phase endocytosis in S. cerevisiae.
AB  - Vrp1p (yeast WIP) forms a protein complex with Las17p (yeast WASP), however the
      physiological significance of the interaction has not been fully characterized.
      Vrp1p residues, (788)MPKPR(792) are essential for Vrp1p-Las17p interaction. While
      C-Vrp1p(364-817) complements all the defects of the vrp1Delta strain, C-Vrp1p(364
      817)(5A) ((788)AAAAA(792)) does not complement any of the defects, due to its
      inability to localize to cortical patches. Targeting C-Vrp1p(364-817)(5A) to
      membranes using CAAX motif (C-Vrp1p(364-817)(5A)-CAAX) rescued the growth and
      endocytosis defect but not the actin patch polarization defect of vrp1Delta.
      Vrp1p can localize to cortical patches, either by binding to Las17p through LBD
      (Las17 Binding Domain, Vrp1p(760-817)) or independent of Las17p through residues
      in N-Vrp1p(1-364). Unlike Vrp1p, Vrp1p(5A) localizes poorly to cortical patches
      and complements all the defects of vrp1Delta strain except actin patch
      polarization at elevated temperature. N-Vrp1p(1-364) complements all the defects
      of vrp1Delta strain except the actin patch polarization defect while N-Vrp1p(1
      364)-LBD fusion protein complements all the defects. Thus our results show that
      while both Vrp1p and Las17p are essential for many cellular processes, the two
      proteins do not necessarily have to bind to each other to carry out these
      cellular functions. However, Las17p-Vrp1p interaction is essential for actin
      patch polarization at elevated temperature.

PMID- 20816902
TI  - Vaccination with a modified vaccinia virus Ankara (MVA)-vectored HIV-1 immunogen
      induces modest vector-specific T cell responses in human subjects.
AB  - We investigated whether vaccination of healthy HIV-seronegative and HIV-1
      seropositive antiretroviral therapy-treated subjects with recombinant modified
      vaccinia virus Ankara expressing an HIV-1 immunogen (MVA.HIVA) induced MVA
      specific T cell responses. Using IFN-gamma Elispot assays, we observed new or
      increased responses to MVA virus in 52% of HIV-seronegative subjects and 93% HIV
      1 seropositive subjects; MVA-specific T cell frequencies were generally low and
      correlated poorly with T cell responses to the HIV-1 immunogen. In two vaccinees,
      responses were mapped to CD8+ T cell epitopes present in replication-competent
      vaccinia virus. These data support further evaluation of MVA as a viral vector
      for HIV-1 immunogens.

PMID- 20816903
TI  - Botulinum neurotoxin neutralizing activity of immune globulin (IG) purified from
      clinical volunteers vaccinated with recombinant botulinum vaccine (rBV A/B).
AB  - The basis for efficacy of the recombinant botulinum vaccine, serotypes A and B
      (rBV A/B) is that neutralizing antibodies induced by vaccination bind to
      botulinum neurotoxin complex serotype A, subtype A1 (BoNT/A1) and serotype B,
      subtype B1 (BoNT/B1) and prevent their actions at cholinergic neurons. The
      protective capacity of BoNT/A1 and BoNT/B1 neutralizing antibodies derived from
      the serum of clinical volunteers vaccinated with rBV A/B was evaluated in a
      guinea pig passive transfer model and a mouse bioassay. Guinea pigs passively
      immunized to achieve circulating neutralizing antibody concentration (NAC) levels
      representing the lowest measurable concentrations for BoNT/A1 and BoNT/B1 were
      protected against an intramuscular (IM) challenge more than 10 times the guinea
      pig IM median lethal dosage for BoNT/A1 and BoNT/B1. The passively immunized
      guinea pigs were asymptomatic during the 14-day post-challenge observation
      period. Control guinea pigs died within 48 h after challenge. Calculation of
      neutralizing efficiency of antibodies using results from a mouse bioassay
      indicated that a simple linearly proportional relationship does not exist between
      NAC level and the amount of BoNT neutralized. Based on this finding, estimates of
      level of protection must consider variability in BoNT neutralizing efficiency at
      different NAC levels. The protective capacity of human BoNT/A1 and BoNT/B1
      neutralizing antibodies induced by rBV A/B vaccination was verified in a guinea
      pig passive immunization model. Additionally, estimates of the neutralizing
      efficiency have been established for BoNT/A1 and BoNT/B1 neutralizing antibodies
      obtained from clinical volunteers vaccinated with the rBV A/B.

PMID- 20816904
TI  - Molecular design of LPS-binding peptides.
AB  - Lipopolysaccharide (LPS), a major constituent of the outer membrane of Gram
      negative bacteria, is highly toxic and can cause sepsis or septic shock.
      Therefore, detection of LPS and the ability to neutralize its toxicity is
      important. We previously obtained a strong LPS-binding peptide, Li5-001, using
      the phage display method (Matsumoto et al., 2010. J. Microbiol. Methods. 82, 54
      58). We modified the sequence the amino acid sequence of this peptide
      (KNYSSSISSIHAC), by replacing and deleting amino acids to obtain higher LPS
      binding affinity and greater resistance to protease digestion. Consequently we
      obtained a dodecapeptide, Li5-025 (K'YSSSISSIRAC', K' and C' are D-forms of K and
      C, respectively) which showed a high affinity for LPS, approximately 1000 folds
      higher affinity than Li5-001 and Kd value of 0.01 nM. By replacing both N- and C
      terminal amino acids from L-type to D-type, the peptide was rendered resistant to
      protease digestion without altering its overall binding capacity.

PMID- 20816905
TI  - A PCR-based toolbox for the culture-independent quantification of total bacterial
      abundances in plant environments.
AB  - A major obstacle in the culture-independent estimation of the abundance of
      bacteria associated with plants is contamination with plant organelles, which
      precludes the use of universal rRNA bacterial primers in quantitative PCR
      applications. We present here a PCR-based method that allows a priori
      determination of the degree of chloroplast and mitochondrial contamination in DNA
      samples from plant environments. It is based on differential digestibility of
      chloroplast, mitochondrial and bacterial small subunit rRNA gene amplicons with
      the restriction enzymes AfeI and BbvCI. Using this method, we demonstrated for
      field-grown lettuce plants that even a gentle washing protocol, designed to
      recover the microbial community and its metagenome from the leaf surface,
      resulted in substantial contamination with chloroplast DNA. This finding cautions
      against the use of universal primer pairs that do not exclude chloroplast DNA
      from amplification, because they risk overestimation of bacterial population
      sizes. In contrast, contamination with mitochondrial 18S rRNA was minor in the
      lettuce phyllosphere. These findings were confirmed by real-time PCR using primer
      sets specific for small subunit rRNA genes from bacteria, chloroplasts, and
      mitochondria. Based on these results, we propose two primer pairs (534f/783r and
      mito1345f/mito1430r) which between them offer an indirect means of faithfully
      estimating bacterial abundances on plants, by deduction of the
      mito1345f/mito1430r-based mitochondrial count from that obtained with 534f/783r,
      which amplifies both bacterial and mitochondrial DNA but excludes chloroplast. In
      this manner, we estimated the number of total bacteria on most leaves of field
      grown lettuce to be between 10(5) and 10(6) g(-1) of leaf, which was 1-3 orders
      of magnitudes higher than the number of colony-forming units that were retrieved
      from the same leaf surfaces on agar plates.

PMID- 20816907
TI  - Up-regulation of caveolin-1 and blood-brain barrier breakdown are attenuated by N
      acetylcysteine in thiamine deficiency.
AB  - Wernicke's encephalopathy is a cerebral metabolic disorder caused by thiamine
      (vitamin B1) deficiency (TD). Neuropathologic consequences of TD include region
      selective neuronal cell loss and blood-brain barrier (BBB) breakdown. Caveolin-1
      is involved in the regulation of tight junction proteins and BBB permeability,
      and is modulated by oxidative stress, a feature of vulnerable brain regions in
      TD. We hypothesized that TD-related oxidative stress alters BBB integrity via
      induction of the caveolin-1 pathway. TD was induced in C57BL6 mice by treatment
      with a thiamine-deficient diet and administration of the thiamine antagonist
      pyrithiamine, in the absence or presence of the antioxidant N-acetylcysteine
      (NAC). A significant and focal increase in both caveolin-1 gene and protein
      expression was detected in the thalamus of thiamine-deficient mice, concomitant
      with IgG extravasation. Reduction of oxidative stress by NAC, as shown by
      normalization of reduced glutathione levels and attenuation of endothelial heme
      oxygenase-1 and nitric oxide synthase expression, resulted in prevention of the
      up-regulation of caveolin-1 in TD. Normalization of caveolin-1 levels by NAC was
      accompanied by a reduction in BBB breakdown, indicated by decreased IgG
      extravasation, normalization of occludin levels and prevention of matrix
      metalloproteinase-9 up-regulation. These findings demonstrate a role for caveolin
      1 in TD pathogenesis, and suggest that oxidative stress contributes to BBB
      alterations in TD via modulation of this pathway.

PMID- 20816906
TI  - Methods to assess stem cell lineage, fate and function.
AB  - Stem cell therapy has the potential to regenerate injured tissue. For stem cells
      to achieve their full therapeutic potential, stem cells must differentiate into
      the target cell, reach the site of injury, survive, and engraft. To fully
      characterize these cells, evaluation of cell morphology, lineage specific
      markers, cell specific function, and gene expression must be performed. To
      monitor survival and engraftment, cell fate imaging is vital. Only then can organ
      specific function be evaluated to determine the effectiveness of therapy. In this
      review, we will discuss methods for evaluating the function of transplanted cells
      for restoring the heart, nervous system, and pancreas. We will also highlight the
      specific challenges facing these potential therapeutic areas.

PMID- 20816908
TI  - Familial amyotrophic lateral sclerosis (FALS)-linked SOD1 mutation accelerates
      neuronal cell death by activating cleavage of caspase-4 under ER stress in an in
      vitro model of FALS.
AB  - Recently, endoplasmic reticulum (ER) dysfunction has been implicated in the
      pathogenesis of familial amyotrophic lateral sclerosis (FALS). Although up
      regulation of caspase-12 has been reported in G93A SOD1 transgenic mice, it is
      controversial whether similar mechanisms operate in human FALS. We found that ER
      stress in cells stably expressing L84V SOD1 induces neuronal cell death and
      accelerates cleavage of caspase-4. We also detected oligomer formation of L84V
      SOD1 in L84V SOD1-expressing human neuroblastoma cells. These findings show that
      ER stress in L84V SOD1-expressing human cells causes the aggregation and
      inclusion bodies of L84V SOD1 to induce neuronal death through the accelerated
      cleavage of caspase-4.

PMID- 20816909
TI  - Predicted critical environmental concentrations for 500 pharmaceuticals.
AB  - A growing number of pharmaceuticals are found in surface waters worldwide,
      raising concerns about their effects on aquatic organisms and it is a major
      challenge to develop a rational strategy for prioritizing drugs on which to focus
      the most extensive environmental research efforts. However, in contrast to most
      other chemicals, very good understanding of the human potency of pharmaceuticals
      has been obtained through efficacy and safety testing. Assuming that a drug acts
      primarily through the same target(s) also in a non-target species, it would be
      possible to predict the likelihood for pharmacological interactions in wildlife.
      Among aquatic organisms, fish most often share drug targets with humans. In this
      study, we have calculated the predicted critical environmental concentration
      (CECs), i.e. the surface water concentration expected to cause a pharmacological
      effect in fish, for 500 pharmaceuticals, assuming equivalent pharmacological
      activity. The CECs are based on literature data on human potencies together with
      a predicted bioconcentration factor in fish for each drug based on lipophilicity.
      We propose that CECs could be used as preliminary indicators of specific drugs'
      potential to cause adverse pharmacological effects at specific water
      concentrations, used when selecting pharmaceuticals to include in screening
      campaigns and for assessing relevant detection limits.

PMID- 20816911
TI  - Sulforaphane modulates the expression of Cyp6a2 and Cyp6g1 in larvae of the ST
      and HB crosses of the Drosophila wing spot test and is genotoxic in the ST cross.
AB  - Constitutive overexpression of Cyp6g1 and Cyp6a2 genes in DDT-resistant line
      Oregon-flare of the Drosophila melanogaster wing spot test (SMART) has been
      reported. Cyp6g1 and Cyp6a2 expression levels were compared against the beta
      actin gene in the standard (ST) and high bioactivation (HB) crosses of the
      Somatic Mutation and Recombination test (SMART) treated with sulforaphane or
      phenobarbital as the control inductor. The CYP450s' enzymatic activity was
      determined by overall NADH consumption. The expression levels of both genes and
      the CYP450s activity was higher in the HB cross. The Cyp6g1 levels were higher
      than those of Cyp6a2 in both crosses, but lower than the expression of beta
      actin. Sulforaphane decreased Cyp6g1 in the HB cross and increased it in the ST
      cross; Cyp6a2 expression was inhibited in the ST cross. Sulforaphane resulted
      mutagenic in the ST cross, which could be related to the inhibition of Cyp6a2.
      Phenobarbital did not modify the Cyp6g1 levels but increased the Cyp6a2 and
      CYP450s basal activity. Although the transcript levels were always higher in the
      HB cross than in the ST, the expression of Cyp6a2 and Cyp6g1 was not constitutive
      and was independent one from the other. Sulforaphane modulated both genes in a
      differential way in each cross and, in contrast to its putative protective
      effect, it resulted to be mutagenic.

PMID- 20816912
TI  - Caffeine enhances working memory for extraverts.
AB  - Using a randomized double-blind placebo-controlled design we examined the effects
      of caffeine on working memory (WM) as a function of extraverted personality.
      Participants (N=59) received 200mg of caffeine and placebo in counterbalanced
      order over two sessions prior to completing a 'N-Back' WM paradigm. Findings
      revealed that caffeine administration relative to the placebo condition resulted
      in heightened WM performance, but only for extraverted participants. We suggest
      based on previous theory and research that dopamine function (DA) may be the most
      plausible mechanism underlying this finding.

PMID- 20816913
TI  - Motor inhibition and response expectancy: a Laplacian ERP study.
AB  - In between-hand choice reaction time tasks, the motor cortex involved in the
      required response (contralateral) has been shown to be activated while the motor
      cortex involved in the non-required response (ipsilateral) has been shown to be
      inhibited. The aim of the present study was to test the hypothesis that
      ipsilateral inhibition reflects an active mechanism aimed at preventing errors.
      To this end, the risk of committing errors in between-hand choice reaction time
      tasks was manipulated by introducing a response probability bias. The surface
      Laplacian transforms of electroencephalographic waves recorded over the motor
      cortices, contralateral and ipsilateral to the responding hand were compared.
      Results showed that contralateral activation was not modulated by the risk of
      committing errors while ipsilateral inhibition was sensitive to this risk in a
      gradual manner: the higher the risk, the stronger the inhibition.

PMID- 20816914
TI  - Chemokine (C-C) motif ligand 20 is regulated by PGF(2alpha)-F-prostanoid receptor
      signalling in endometrial adenocarcinoma and promotes cell proliferation.
AB  - Prostaglandin F(2alpha) (PGF(2alpha)) is an inflammatory mediator which signals
      through a G-protein coupled receptor, the F-prostanoid (FP) receptor. We have
      previously shown elevated FP receptor expression in endometrial adenocarcinoma, a
      common gynaecological malignancy in Western countries. In this study, the
      expression of the chemokine CC motif Ligand 20 (CCL20) was determined to be
      regulated by PGF(2alpha)-FP receptor signalling in endometrial adenocarcinoma
      explants and cell line, and expression of CCL20 and its receptor CCR6 was
      elevated in endometrial adenocarcinoma compared to non-malignant endometrium.
      Both CCL20 and CCR6 were localised to neoplastic endometrial epithelial cells.
      The induction of CCL20 expression by PGF(2alpha)-FP signalling in an endometrial
      adenocarcinoma cell line stably expressing the FP receptor (FPS cells) was found
      to be dependent on the intracellular signalling of Gq, EGFR, ERK, calcineurin and
      nuclear factor of activated T-cells (NFAT) proteins. The treatment of FPS cells
      with recombinant CCL20 caused a significant increase in proliferation. Therefore
      these data demonstrate a role for the FP receptor in regulation of the chemokine
      CCL20, which can mediate proliferation of endometrial adenocarcinoma epithelial
      cells.

PMID- 20816915
TI  - Characterization of steroid receptor coactivator in sea urchin,
      Strongylocentrotus nudus, and its involvement in embryonic development.
AB  - Ligand-bound nuclear receptors (NRs) recruit coactivators such as members of the
      p160 steroid receptor coactivator (SRC) family and cyclic AMP responsive element
      binding protein (CREB)-binding protein (CBP) to specific enhancer elements and
      activate target gene transcription. In the present study, we isolated a novel SRC
      from the sea urchin Strongylocentrotus nudus (SnSRC) by using the ligand-binding
      domain of retinoid X receptor as a bait in a yeast two-hybrid screening. The
      SnSRC and vertebrate SRCs are different in size but share the overall
      characteristic domains, such as NR interacting domain (NID), CBP-binding and
      glutamine-rich regions. SnSRC mRNA showed highest expression levels at the 32
      cell, 64-cell and pluteus larval stages. Full-length SnSRC (1992 amino acids)
      interacted with several NRs, including sea urchin estrogen receptor-related
      receptor (ERR), human and masu salmon estrogen receptors (ERalpha), mouse
      ERRgamma, rat glucocorticoid receptor alpha, and rat thyroid receptor beta. The
      SnSRC possesses two functional NIDs, both of which are dependent on their core
      LxxLL motifs. Furthermore, preferential interacting domains for ERalpha in the
      SnSRC are located in the central LxxLL motifs, revealed by the truncation and
      mutagenesis studies. Strikingly, the SnSRC has a single transcription activation
      domain, which interacts with CBP, a transcriptional integrator. In addition,
      transient knockdown of the SnSRC gene in the sea urchin embryo using morpholino
      antisense RNA induced abnormal phenotypes at gastrulation stage such as the lack
      of primary invagitation and exogastrulation. These results suggest that the SnSRC
      is a new member of the SRC family and plays an important role during early
      embryonic development.

PMID- 20816916
TI  - 2-Methoxyestradiol: new perspectives in colon carcinoma treatment.
AB  - Colon carcinoma represents a major problem in oncology, since this type of cancer
      responds poorly to conventional chemotherapy. Many groups are actively involved
      in the search of new experimental strategies to bypass this problem. We
      investigated the effects of 2-methoxyestradiol (2-ME), which derives from the
      NADPH-dependent cytochrome P450 metabolism of 17beta-estradiol. This compound has
      raised much interest in the past few decades for its inhibitory effects on the
      growth of cancer cells of different origin; however, little is known about its
      use on colon carcinoma-derived cell lines. In the present study, we investigated
      the effects of 2-ME on cell proliferation and cell cycle of two human colon
      carcinoma cell lines, namely HCT116 and SW613-B3. Our results showed a net anti
      proliferative effect of 2-ME on both cell lines, which is accompanied by cell
      cycle arrest; moreover, we demonstrated that 2-ME is able to induce apoptosis as
      well as autophagy. This body of evidence points out that 2-ME could be considered
      as a promising tool against colon carcinoma.

PMID- 20816917
TI  - Study of the origin of short- and long-latency SSEP during recovery from brain
      ischemia in a rat model.
AB  - Somatosensory evoked potentials (SSEPs) have been established as an
      electrophysiological tool for the prognostication of neurological outcome in
      patients with hypoxic-ischemic brain injury. The early and late responses in
      SSEPs reflect the sequential activation of neural structures along the
      somatosensory pathway. This study reports that the SSEP can be separated into
      early (short-latency, SL) and late (long-latency, LL) responses using independent
      component analysis (ICA), based on the assumption that these components are
      generated from different neural sources. Moreover, this source separation into
      the SL and LL components allows analysis of electrophysiological response to
      brain injury, even when the SSEPs are severely distorted and SL and LL components
      get mixed. With the help of ICA decomposition and corrected peak estimation, the
      latency of LL-SSEP is shown to be predictive of long-term neurological outcome.
      Further, it is shown that the recovery processes of SL- and LL-SSEPs follow
      different dynamics, with the SL-SSEP restored earlier than LL-SSEP. We predict
      that the SL- and LL-SSEPs reflect the timing of the progression of evoked
      response through the thalamocortical pathway and as such respond differently
      depending upon injury and recovery of the thalamic and cortical regions,
      respectively.

PMID- 20816918
TI  - Valproate attenuates the development of morphine antinociceptive tolerance.
AB  - Morphine is a potent opioid analgesic. Repeated administration of morphine
      induces tolerance, thus reducing the effectiveness of analgesic treatment.
      Although some adjuvant analgesics can increase morphine analgesia, the precise
      molecular mechanism behind their effects remains unclear. Opioids bind to the mu
      opioid receptor (MOR). Morphine tolerance may be derived from alterations in the
      intracellular signal transduction after MOR activation. Chronic morphine
      treatment activates glycogen synthase kinase 3beta (GSK3beta), whose inhibition
      diminishes morphine tolerance. Valproate is widely prescribed as an
      anticonvulsant and a mood stabilizer for bipolar disorders because it increases
      the amount of gamma-aminobutyric acid (GABA) in the central nervous system.
      Although the activation of GABAergic neurons may be responsible for the chief
      pharmacologic effect of valproate, recent studies have shown that valproate also
      suppresses GSK3beta activity. We examined the effect of valproate on the
      development of morphine antinociceptive tolerance in a mouse model of thermal
      injury. Mice were treated with morphine alone or with morphine and valproate
      twice daily for 5 days. The resulting antinociceptive effects were assessed using
      a hot plate test. While mice treated with morphine developed tolerance, co
      administration of valproate attenuated the development of tolerance and impaired
      the activation of GSK3beta in mice brains. Valproate alone did not show analgesic
      effects; nevertheless, it functioned as an adjuvant analgesic to prevent the
      development of morphine tolerance. These results suggest that the modulation of
      GSK3beta activity by valproate may be useful and may play a role in the
      prevention of morphine tolerance.

PMID- 20816919
TI  - Effect of prematurity and intrauterine growth restriction on H-reflex recovery
      cycle in neonates.
AB  - OBJECTIVE: The purpose of this work was to assess the effects of prematurity and
      intrauterine growth restriction on spinal cord synapses using H-reflex. METHODS:
      33 babies were investigated at birth. 14 were full term appropriate for
      gestational age (FT AGA), 10 were full term intrauterine growth restricted (FT
      IUGR) and 9 were preterm appropriate for gestational age (PT AGA). The maximum
      amplitude of H-reflex (Hmax), H-reflex latency (HRL), H/M ratio, H-reflex
      conduction velocity (HRCV), and H-reflex response to double stimuli (conditioning
      and test) for H-reflex recovery cycle (HRRC) were recorded in right lower limb
      (soleus muscle) in all the three groups. RESULTS: Percentage recovery values of H
      reflex were significantly higher in FT AGA and FT IUGR babies compared to PT AGA
      neonates for most of inter-stimulus intervals. No significant differences were
      observed in H-reflex parameters between FT AGA and FT IUGR groups, but HRL and
      HRCV were significantly affected in PT AGA group. CONCLUSIONS: Delayed H-reflex
      recovery in preterms may be due to a prolonged state of neurotransmitter delay in
      Ia terminals following initial activation by the conditioning stimuli. The cause
      of such prolonged depletion of neurotransmitters could be attributed to a poor
      neurotransmitter store in synaptic vesicles of spinal cord in preterm neonates.

PMID- 20816920
TI  - Mutational analysis of GIGYF2, ATP13A2 and GBA genes in Brazilian patients with
      early-onset Parkinson's disease.
AB  - In the last decade, several genes have been linked to Parkinson's disease (PD),
      including GIGYF2, ATP13A2 and GBA. To explore whether mutations in these genes
      contribute to development of PD in the Brazilian population, we screened 110
      patients with early-onset PD. No clearly pathogenic mutations were identified in
      ATP13A2 and GIGYF2. In contrast, we identified a significantly higher frequency
      of known pathogenic mutations in GBA gene among the PD cases (6/110=5.4%) when
      compared to the control group (0/155) (P=0.0047). Our results strongly support an
      association between GBA gene mutations and an increased risk of PD. Mutations in
      GIGYF2 and ATP13A2 do not seem to represent a risk factor to the development of
      PD in the Brazilian population. Considering the scarcity of studies on GIGYF2,
      ATP13A2 and GBA mutation frequency in Latin American countries, we present
      significant data about the contribution of these genes to PD susceptibility.

PMID- 20816921
TI  - Clustered K+ channel complexes in axons.
AB  - Voltage-gated K+ (Kv) channels regulate diverse neuronal properties including
      action potential threshold, amplitude, and duration, frequency of firing,
      neurotransmitter release, and resting membrane potential. In axons, Kv channels
      are clustered at a variety of functionally important sites including axon initial
      segments, juxtaparanodes of myelinated axons, nodes of Ranvier, and cerebellar
      basket cell terminals. These channels are part of larger protein complexes that
      include cell adhesion molecules and scaffolding proteins. These interacting
      proteins play important roles in recruiting K+ channels to distinct axonal
      domains. Here, I review the composition, functions, and mechanism of localization
      of these K+ channel complexes in axons.

PMID- 20816923
TI  - Adult neurogenesis is reduced in the dorsal hippocampus of rats displaying
      learned helplessness behavior.
AB  - Clinical and preclinical studies suggest that the hippocampus has a role in the
      pathophysiology of major depression. In the learned helplessness (LH) animal
      model of depression after inescapable shocks (ISs) animals that display LH
      behavior have reduced cell proliferation in the hippocampus; this effect can be
      reversed by antidepressant treatment. Using this model, we compared rats that
      displayed LH behavior and rats that did not show LH behavior (NoLH) after ISs to
      determine whether reduced hippocampal cell proliferation is associated with the
      manifestation of LH behavior or is a general response to stress. Specifically, we
      examined cell proliferation, neurogenesis, and synaptic function in dorsal and
      ventral hippocampus of LH and NoLH animals and control rats that were not
      shocked. The LH rats had showed reduced cell proliferation, neurogenesis, and
      synaptic transmission in the dorsal hippocampus, whereas no changes were seen in
      the ventral hippocampus. These changes were not observed in the NoLH animals. In
      a group of NoLH rats that received the same amount of electrical shock as the LH
      rats to control for the unequal shocks received in these two groups, we observed
      changes in Ki-67(+) cells associated with acute stress. We conclude that reduced
      hippocampal cell proliferation and neurogenesis are associated with the
      manifestation of LH behavior and that the dorsal hippocampus is the most affected
      area.

PMID- 20816922
TI  - Signaling complexes of voltage-gated sodium and calcium channels.
AB  - Membrane depolarization and intracellular Ca(2+) transients generated by
      activation of voltage-gated Na+ and Ca(2+) channels are local signals, which
      initiate physiological processes such as action potential conduction, synaptic
      transmission, and excitation-contraction coupling. Targeting of effector proteins
      and regulatory proteins to ion channels is an important mechanism to ensure
      speed, specificity, and precise regulation of signaling events in response to
      local stimuli. This article reviews experimental results showing that Na+ and
      Ca(2+) channels form local signaling complexes, in which effector proteins,
      anchoring proteins, and regulatory proteins interact directly with ion channels.
      The intracellular domains of these channels serve as signaling platforms,
      mediating their participation in intracellular signaling processes. These protein
      protein interactions are important for regulation of cellular plasticity through
      modulation of Na+ channel function in brain neurons, for short-term synaptic
      plasticity through modulation of presynaptic Ca(V)2 channels, and for the fight
      or-flight response through regulation of postsynaptic Ca(V)1 channels in skeletal
      and cardiac muscle. These localized signaling complexes are essential for normal
      function and regulation of electrical excitability, synaptic transmission, and
      excitation-contraction coupling.

PMID- 20816924
TI  - A developmental characterization of mesolimbocortical serotonergic gene
      expression changes following early immune challenge.
AB  - An immunogenic challenge during early postnatal development leads to long-term
      changes in behavioural and physiological measures reflecting enhanced
      emotionality and anxiety. Altered CNS serotonin (5-HT) signalling during the
      third postnatal week is thought to modify the developing neurocircuitry governing
      anxiety-like behaviour. Changes in 5-HT signalling during this time window may
      underlie increased emotionality reported in early immune challenge rodents. Here
      we examine both the spatial and temporal profile of 5-HT related gene expression,
      including 5HT1A, 2A, 2C receptors, the 5-HT transporter (5HTT), and tryptophan
      hydroxylase 2 (TPH2) during early development (postnatal day [P]14, P17, P21,
      P28) in mice challenged with lipopolysaccharide (LPS) during the first postnatal
      week. Expression levels were measured using in situ hybridization in regions
      associated with mediating emotive behaviours: the dorsal raphe (DR), hippocampus,
      amygdala, and prefrontal cortex (PFC). Increased TPH2 and 5HTT expression in the
      ventrolateral region of the DR of LPS-mice accompanied decreased expression of
      ventral DR 5HT1A and dorsal DR 5HTT. In the forebrain, 5HT1A and 2A receptors
      were increased, whereas 5HT2C receptors were decreased in the hippocampus.
      Decreased mRNA expression of 5HT2C was detected in the amygdala and PFC of LPS
      treated pups; 5HT1A was increased in the PFC. The majority of these changes were
      restricted to P14-21. These transient changes in 5-HT expression coincide with
      the critical time window in which 5-HT disturbance leads to permanent
      modification of anxiety-related behaviours. This suggests that alterations in CNS
      5-HT during development may underlie the enhanced emotionality associated with an
      early immune challenge.

PMID- 20816925
TI  - Pregnenolone sulfate enhances spontaneous glutamate release by inducing
      presynaptic Ca2+-induced Ca2+ release.
AB  - Pregnenolone sulfate (PS) acts as an excitatory neuromodulator and has a variety
      of neuropharmacological actions, such as memory enhancement and convulsant
      effects. In the present study, we investigated the effect of PS on glutamatergic
      spontaneous excitatory postsynaptic currents (sEPSCs) in acutely isolated dentate
      gyrus (DG) hilar neurons by use of a conventional whole-cell patch-clamp
      technique. PS significantly increased sEPSC frequency in a concentration
      dependent manner without affecting the current amplitude, suggesting that PS acts
      presynaptically to increase the probability of spontaneous glutamate release.
      However, known molecular targets of PS, such as alpha7 nicotinic ACh, NMDA,
      sigma1 receptors and voltage-dependent Ca(2+) channels, were not responsible for
      the PS-induced increase in sEPSC frequency. In contrast, the PS-induced increase
      in sEPSC frequency was completely occluded in a Ca(2+)-free external solution,
      and was significantly reduced by either the depletion of presynaptic Ca(2+)
      stores or the blockade of ryanodine receptors, suggesting that PS elicits Ca(2+)
      induced Ca(2+) release (CICR) within glutamatergic nerve terminals. In addition,
      the PS-induced increase in sEPSC frequency was completely occluded by transient
      receptor potential (TRP) channel blockers. These data suggest that PS increases
      spontaneous glutamate release onto acutely isolated hilar neurons via presynaptic
      CICR, which was triggered by the influx of Ca(2+) through presynaptic TRP
      channels. The PS-induced modulation of excitatory transmission onto hilar neurons
      could have a broad impact on the excitability of hilar neurons and affect the
      pathophysiological functions mediated by the hippocampus.

PMID- 20816926
TI  - Antipsychotic drugs dose-dependently suppress the spontaneous hyperactivity of
      the chakragati mouse.
AB  - The chakragati (ckr) mouse has been proposed as a model of aspects of
      schizophrenia. The mice, created serendipitously as a result of a transgenic
      insertional mutation, exhibit spontaneous circling, hyperactivity, hypertone of
      the dopamine system, reduced social interactions, enlarged lateral ventricles,
      deficits in pre-pulse inhibition of acoustic startle and deficits in latent
      inhibition of conditioned learning. In this study, the dose-dependent effects of
      antipsychotic drugs (haloperidol, pimozide, risperidone, clozapine, olanzapine,
      ziprasidone, quetiapine and aripiprazole) on the spontaneous hyperactivity of the
      mice were investigated. All the antipsychotic drugs tested dose-dependently
      suppressed spontaneous hyperactivity. Aripriprazole, which is known to be a
      dopamine D2 receptor partial agonist, exhibited a tri-phasic dose-response,
      initially suppressing hyperactivity at low doses, having little effect on
      hyperactivity at intermediate doses, and suppressing activity again at high
      doses. These data suggest that the spontaneous circling and hyperactivity of the
      ckr mouse may allow screening of candidate antipsychotic compounds,
      distinguishing compounds with aripriprazole-like profiles.

PMID- 20816927
TI  - Phlebotomine sand fly population dynamics in a leishmaniasis endemic peri-urban
      area in southern Italy.
AB  - A 2-year survey was carried out from May to November 2008 and 2009 to study the
      sand fly species composition, its seasonal phenology and density in Apulia region
      (southern, Italy). The study was conducted in a dog shelter located in a new
      residential urban district where Leishmania infantum is endemic. Sand flies were
      collected using sticky traps from May to November, at about 7-day intervals.
      Temperature and relative humidity were recorded daily. In December 2008, general
      environmental improvements (e.g., the ground was covered with gravel and the
      vegetation present inside the cages was removed to facilitate cleaning) were made
      in the study area. The most diffused species during the whole study period were
      Phlebotomus perniciosus (2008, n=248, 49.4%; 2009, n=254, 50.6%) followed by
      Phlebotomus neglectus (2008, n=76, 39.8%; 2009, n=115, 60.2%) and Phlebotomus
      papatasi (2008, n=5, 50.0%; 2009, n=5, 50.0%). Four specimens of Phlebotomus
      perfiliewi were collected only in the first year. The number of Sergentomyia
      minuta specimens collected increased considerably in the second (n=548, 86.2%) in
      comparison to the first year (n=88, 13.8%). The highest number of phlebotomine
      sand flies was collected in July and August when a mean temperature from 27.09 to
      28.02 degrees C and mean relative humidity from 47.28 to 56.36% were recorded.
      The variations in phlebotomine sand fly species diversity and abundance recorded
      in this study were related to climatic and environmental factors. Data here
      presented confirm that sand flies easily adapt to the urban environments and that
      the may represent a public health concern for L. infantum and other pathogen
      transmission also in similar urban environment of southern Europe.

PMID- 20816928
TI  - Influence of size and surface roughness of large lactose carrier particles in dry
      powder inhaler formulations.
AB  - The objective of this study was to determine the effect of both carrier particle
      size and surface roughness on the aerosol performance of dry powder formulations.
      Two morphologically distinct grades of lactose, anhydrous (AN) and granulated
      (GR), were fractionated into 11 discreet sizes up to 300MUm, and separately
      employed as carriers in 2% (w/w) budesonide blends. In vitro deposition studies
      were performed at 60Lmin(-1) with an Aerolizer((r)) DPI. It was found that large
      carriers can improve dispersion performance, although the effect is more
      pronounced with greater surface roughness. AN carriers exhibited minimal surface
      roughness and generally behaved as predicted from the literature, with the
      smaller carriers outperforming their larger counterparts. In contrast, GR
      carriers had a high degree of surface roughness, and the dispersion performance
      of larger carriers exceeded that of the smaller size fractions. Comparing the two
      lactose grades, AN carriers deposited a greater fraction of the total dose up to
      the 90-125MUm size range, when they were surpassed in performance by the GR
      carriers. These results suggest that the mechanism of drug detachment varies with
      the physical properties of the carrier particle population, where surface
      roughness can alter the predominant detachment mechanism to favor larger carrier
      particle diameters.

PMID- 20816929
TI  - Modeling of dispersed-drug delivery from planar polymeric systems: optimizing
      analytical solutions.
AB  - Analytical solutions for the case of controlled dispersed-drug release from
      planar non-erodible polymeric matrices, based on Refined Integral Method, are
      presented. A new adjusting equation is used for the dissolved drug concentration
      profile in the depletion zone. The set of equations match the available exact
      solution. In order to illustrate the usefulness of this model, comparisons with
      experimental profiles reported in the literature are presented. The obtained
      results show that the model can be employed in a broad range of applicability.

PMID- 20816930
TI  - Mixed backbone antisense glucosylceramide synthase oligonucleotide (MBO-asGCS)
      loaded solid lipid nanoparticles: in vitro characterization and reversal of
      multidrug resistance in NCI/ADR-RES cells.
AB  - In this study, solid lipid nanoparticles (SLN) loaded with MBO-asGCS
      oligonucleotide were prepared, characterized and evaluated for cytotoxicity
      against NCI/ADR-RES human ovary cancer cells. Two types of cetyltrimethyl
      ammonium bromide (CTAB) stabilized SLN, with or without ceramide VI, were
      prepared by mixed homogenization/ultrasonication technique. Complexes were
      characterized for size, zeta-potential, and stability in biorelevant media and
      against DNaseI activity. Binding and release studies were further confirmed by
      gel electrophoresis. Cytotoxicity of the SLN against NCI/ADR-RES cells was
      evaluated by quantizing ATP. SLN with ceramide VI had lower particle size (74.6
      nm) with improved stability in RPMI media when compared to reference SLN without
      ceramide VI (167.16 nm). Both SLN however had similar cytotoxicity profile with
      an optimum binding at CTAB to MBO-asGCS ratio of 6:1. Blank SLN, and free MBO
      asGCS in the presence and absence of free doxorubicin had insignificant effect on
      the viability of NCI/ADR-RES cells. However, when cells were concurrently treated
      with MBO-asGCS loaded SLN and free doxorubicin, cell viability significantly
      decreased to approximately 12%. These results suggested that SLN enhanced
      internalization and uptake of MBO-asGCS oligonucleotide, which led to the
      downregulation of GCS and subsequently reversing the resistance of the cells to
      doxorubicin.

PMID- 20816931
TI  - Molecular cloning of amphioxus uncoupling protein and assessment of its
      uncoupling activity using a yeast heterologous expression system.
AB  - The present study describes the molecular cloning of a novel cDNA fragment from
      amphioxus (Branchiostoma belcheri) encoding a 343-amino acid protein that is
      highly homologous to human uncoupling proteins (UCP), this protein is therefore
      named amphioxus UCP. This amphioxus UCP shares more homology with and is
      phylogenetically more related to mammalian UCP2 as compared with UCP1. To further
      assess the functional similarity of amphioxus UCP to mammalian UCP1 and -2, the
      amphioxus UCP, rat UCP1, and human UCP2 were separately expressed in
      Saccharomyces cerevisiae, and the recombinant yeast mitochondria were isolated
      and assayed for the state 4 respiration rate and proton leak, using pYES2 empty
      vector as the control. UCP1 increased the state 4 respiration rate by 2.8-fold,
      and the uncoupling activity was strongly inhibited by GDP, while UCP2 and
      amphioxus UCP only increased the state 4 respiration rate by 1.5-fold and 1.7
      fold in a GDP-insensitive manner, moreover, the proton leak kinetics of amphioxus
      UCP was very similar to UCP2, but much different from UCP1. In conclusion, the
      amphioxus UCP has a mild, unregulated uncoupling activity in the yeast system,
      which resembles mammalian UCP2, but not UCP1.

PMID- 20816932
TI  - Relative actin nucleation promotion efficiency by WASP and WAVE proteins in
      endothelial cells.
AB  - The mammalian genome encodes multiple Wiskott-Aldrich syndrome protein
      (WASP)/WASP-family Verprolin homologous (WAVE) proteins. Members of this family
      interact with the actin related protein (Arp) 2/3 complex to promote growth of a
      branched actin network near the plasma membrane or the surface of moving cargos.
      Arp2/3 mediated branching can further lead to formation of comet tails (actin
      rockets). Despite their similar domain structure, different WASP/WAVE family
      members fulfill unique functions that depend on their subcellular location and
      activity levels. We measured the relative efficiency of actin nucleation
      promotion of full-length WASP/WAVE proteins in a cytoplasmic extract from primary
      human umbilical vein endothelial cells (HUVEC). In this assay WAVE2 and WAVE3
      complexes showed higher nucleation efficiency than WAVE1 and N-WASP, indicating
      distinct cellular controls for different family members. Previously, WASP and N
      WASP were the only members that were known to stimulate comet formation. We
      observed that in addition to N-WASP, WAVE3 also induced short actin tails, and
      the other WAVEs induced formation of asymmetric actin shells. Differences in
      shape and structure of actin-based growth may reflect varying ability of
      WASP/WAVE proteins to break symmetry of the actin shell, possibly by differential
      recruitment of actin bundling or severing (pruning or debranching) factors.

PMID- 20816933
TI  - Heterologous expression of thermostable acetylxylan esterase gene from
      Thermobifida fusca and its synergistic action with xylanase for the production of
      xylooligosaccharides.
AB  - The axe gene which encodes an acetylxylan esterase from Thermobifida fusca NTU22,
      was cloned, sequenced and expressed in Escherichia coli. The gene consists of 786
      base pairs and encodes a protein of 262 amino acids. The deduced amino acid
      sequence of the acetylxylan esterase axe exhibited a high degree of similarity
      with BTA-hydrolase from T. fusca DSM43793, esterase from Thermobifida alba and
      lipase from Streptomyces albus. The optimal pH and temperature of the purified
      esterase were 7.5 and 60 degrees C, respectively. Cooperative enzymatic treatment
      of oat-spelt xylan by transformant xylanase and acetylxylan esterase
      significantly increased the xylooligosaccharides production compared with the
      xylanase or acetylxylan esterase action alone. The synergy of transformant
      acetylxylan esterase and xylanase cannot increase the production of reducing
      sugars from lignocellulolytic substrate, bagasse.

PMID- 20816934
TI  - Relationship between blood glucose levels and hepatic Fto mRNA expression in
      mice.
AB  - Common variants in the fat mass and obesity associated (FTO) gene are associated
      with obesity and type 2 diabetes. Fto-deficient mice develop hepatic insulin
      resistance, leading to the hypothesis that hepatic Fto plays a role in the
      regulation of glucose metabolism and that hepatic Fto expression is regulated by
      metabolic states. We found that hepatic Fto mRNA levels were increased by fasting
      in mice. Intraperitoneal glucose injection reduced hepatic Fto mRNA levels
      without significant changes in body weight in fasted mice. The inverse
      correlation between Fto mRNA and glucose remained significant after adjusting for
      body weight. There were positive correlations between hepatic Fto mRNA expression
      and gluconeogenic gene expression. These data support the hypothesis that hepatic
      Fto expression changes in response to metabolic states and glucose reduces
      hepatic Fto mRNA expression independently of body weight. Hepatic Fto may
      participate in the feedback regulation of glucose metabolism via gluconeogenesis.

PMID- 20816935
TI  - Cell migration-promoting and apoptosis-inhibiting activities of Bm-TFF2 require
      distinct structure basis.
AB  - Human trefoil factors (TFFs) play an important role in wound healing, epithelial
      restitution and anti-inflammatory effects in the gastrointestinal tract by
      stimulating cell migration and inhibiting cell apoptosis. In our previous study,
      Bm-TFF2, an amphibian trefoil factor, which is isolated from the skin secretions
      of frog Bombina maxima, has much stronger activities than human TFFs. We believe
      that the expression of the recombinant Bm-TFF2 in vitro is useful to decipher its
      role in amphibian skin repair. Bm-TFF2 contains 12 cysteine residues and has two
      TFF-domains. In this study, we expressed full-length of Bm-TFF2 and its single
      domain truncations (Bm-TFF2-D1 and Bm-TFF2-D2, each contains a single TFF-domain
      of Bm-TFF2). The recombinant proteins, including full-length and its single
      domain truncations of Bm-TFF2, can promote the migration of human epithelial AGS
      cells and wound healing of rat intestinal epithelial IEC-6 cells. However, only
      the full-length of Bm-TFF2, but not its single-domain truncations, can inhibit
      ceramide-induced apoptosis in AGS cells. In summary, it is the first time to use
      the recombinant Bm-TFF2 and its truncations to investigate its structure-function
      relationship. And we report that full-length and each domain of Bm-TFF2 can
      induce cell migration but only the full-length of Bm-TFF2 can suppress apoptosis,
      indicating that cell migration-promoting and apoptosis-inhibiting activities of
      Bm-TFF2 require distinct structure basis.

PMID- 20816936
TI  - Bone morphogenetic protein 6 drives both osteogenesis and chondrogenesis in
      murine adipose-derived mesenchymal cells depending on culture conditions.
AB  - Bone morphogenetic proteins (BMPs) play a dual role as a factor in both bone and
      cartilage development and correspondingly have the therapeutic potential to
      regenerate both tissues. Given this dual nature, previous in vitro research using
      BMPs has relied on distinct media formulations and culture conditions to drive
      undifferentiated cells to the osteogenic or chondrogenic lineage. To isolate the
      impact of culture conditions and to explore the effect of BMP-6 on murine adipose
      derived mesenchymal cells (ASCs), ASCs were seeded in either monolayer or pellets
      in an identical medium containing BMP-6. Results indicate that BMP-6
      differentially promotes osteogenesis and chondrogenesis in ASCs depending on
      culture conditions. BMP-6 potently induced alkaline phosphatase activity and
      mineralization in ASCs cultured in monolayer conditions. In contrast, BMP-6
      enhanced proteoglycan accumulation in ASCs seeded in chondrogenic pellet culture.
      A comparison of gene expression suggests that the differentiating effect of BMP-6
      is specific to the particular culture condition. This study highlights the
      importance of the interactions between chemical signaling and microenvironmental
      cues in directing cell fate.

PMID- 20816937
TI  - AMPA receptor-mediated miniature EPSCs have heterogeneous time courses in orexin
      neurons.
AB  - Glutamate plays a predominant role in regulating the activity of orexin neurons
      that coordinate motivated behaviors, sleep-wake cycle and autonomic functions. To
      gain more insight into the properties of excitatory transmission to orexin
      neurons, whole cell patch clamp recordings were made in rat brain slices and
      quantal analysis of pharmacologically isolated miniature excitatory postsynaptic
      currents (mEPSCs) was performed. In more than half the orexin neurons examined,
      mEPSCs showed heterogeneous time course: some mEPSCs had fast rise and decay
      (fast mEPSC), while some had longer kinetics, smaller amplitude but larger
      integrated area (slow mEPSC). Other orexin neurons showed low frequency mEPSCs
      with uniform, fast kinetics. In the former, distribution histogram of 10-90% rise
      time displayed two peaks, indicating that fast and slow mEPSCs are distinct
      subgroups. Occasionally fast and slow EPSCs would summate, suggesting that they
      arise from different pairs of active zones and postsynaptic receptor clusters. A
      large majority of mEPSCs were mediated by AMPA receptors that are sensitive to
      GYKI 52466 and DNQX. To determine whether synapses that give rise to fast and
      slow mEPSCs are differentially modulated, the D1- and D2-like agonists were
      tested on various parameters of mEPSCs. The agonists altered the frequency as
      previously reported, but had no effect on the rise, decay or area of mEPSC,
      suggesting that dopamine affects fast and slow mEPSCs equally. Given the
      potential physiological impact of EPSC time course on synaptic integration, our
      study raises an interesting possibility that distinct subset of excitatory
      synaptic inputs are processed differently by orexin neurons.

PMID- 20816938
TI  - Seson, a novel zinc finger protein, controls cilia integrity for the LR
      patterning during zebrafish embryogenesis.
AB  - In zebrafish embryos, bilateral symmetry is broken by asymmetric nodal flow
      generated in Kupffer's vesicle (KV), the transient cilia-rich organ, analogous to
      the mouse node. Asymmetric nodal flow induces the asymmetric expression of
      several genes, which are critical for the determination of correct LR body
      patterning. seson encoding three consecutive C2H2 zinc finger protein is
      predominantly expressed in the cilia-rich organs including KV. Inhibition of its
      function by the injection of a seson-specific MO inhibited the left-side biased
      expression of spaw, and resulted in randomization of the heart, gut looping and
      brain laterality. Disruption of the LR patterning in seson morphants appeared to
      be due to severe cilia defects in KV. Seson function was also required for
      ciliogenesis in other tissues such as the pronephros and olfactory organs.
      Collectively, our data suggest that Seson has critical roles in ciliogenesis and
      LR body axis patterning.

PMID- 20816939
TI  - Investigation of riboflavin sensitized degradation of purine and pyrimidine
      derivatives of DNA and RNA under UVA and UVB.
AB  - DNA and RNA undergo photodegradation in UVC (200-290nm) due to direct absorption
      by the purine and pyrimidine bases. Limited effects are observed under UVB (290
      320nm) or UVA (320-400nm). We have observed that an endogenous photosensitizer,
      riboflavin (RF), upon exposure to UVB or UVA can extensively damage the DNA and
      RNA bases. Guanine, uracil, thymine, adenine and cytosine were degraded by 100%,
      82%, 60.4%, 46.3% and 10.3% under UVA (12J) and by 100%, 54.1%, 38.9%, 42.2% and
      <1.0% under UVB (6J), respectively. Guanosine and deoxyguanosine were degraded by
      98+/-1.0% and 80+/-1.0% under UVA (4J) and UVB (12J), respectively. With an
      exception of GMP (53-82%), dGMP (51-88%) and to some extent TMP (3-4%) the
      remaining nucleosides and nucleotides were resistant to RF-induced
      photodecomposition. The photodegradation of G derivatives by RF was 2-fold higher
      than a well known photodynamic agent rose bengal. A comparison of the intensities
      of UVA and UVB sources used in this study with natural sunlight suggests that
      exposure with the latter along with an endogenous photosensitizer can have
      similar effects on DNA and RNA depending upon the duration of exposure.

PMID- 20816940
TI  - The effects of Sceletium tortuosum in an in vivo model of psychological stress.
AB  - AIM OF THE STUDY: Sceletium, and especially Sceletium tortuosum, is traditionally
      used as masticator and thought to have a sedative effect which may be beneficial
      to reduce symptoms of anxiety and/or depression. The current study evaluated the
      scientific merit of these anecdotal claims in an in vivo model of psychological
      stress. MATERIALS AND METHODS: Male Wistar rats were administered either placebo,
      5 or 20 mg/kg/day of Sceletium tortuosum extract for 17 days by daily oral
      gavage. 50% of rats were exposed to repeated restraint stress lasting 1h for the
      last 3 days of treatment. Rat behavioral changes in response to stress were
      assessed using the elevated plus maze on the last day of restraint, immediately
      after the restraint session. Rats were sacrificed 24h after the last restraint
      exposure and whole blood collected. RESULTS: Behavior indicated a limited effect
      of lower dose Sceletium to decrease restraint stress-induced self-soothing
      behavior, as well as to decrease stress-induced corticosterone levels. However,
      increased IL-1beta levels argue against the claim that the plant may act as
      selective serotonin reuptake inhibitor, while this result combined with increased
      levels of C-reactive protein and prostaglandin E(2) suggest intolerance to the
      treatment. Decreased IL-2 and increased IL-10 levels in response to Sceletium
      treatment suggest a suppressive effect on T helper 1 immune function.
      CONCLUSIONS: Although data indicates a limited positive effect of Sceletium on
      restraint-induced anxiety, numerous side-effects were evident. More research is
      required to derive an optimal therapeutic dose.

PMID- 20816941
TI  - Antidiabetic and antioxidant effects of extracts from Potentilla discolor Bunge
      on diabetic rats induced by high fat diet and streptozotocin.
AB  - AIM OF THE STUDY: Potentilla discolor Bunge, commonly found at the north
      temperate and boreal zone, has been used for diabetes in China for a long time.
      Flavonoids and triterpenoids are two major types of compounds in P. discolor.
      This study was designed primarily to investigate the effects of total flavonoids
      extract (TFE) and total triterpenoids extract (TTE) of P. discolor Bunge on blood
      glucose, lipid profiles and antioxidant parameters on diabetic rats induced by
      high fat diet and streptozotocin. MATERIALS AND METHODS: High fat diet-fed and
      streptozotocin-induced diabetic rats were treated with the TFE and TTE for 15
      days, respectively. A range of parameters were tested including fasting blood
      glucose (FBG), serum insulin (SI), blood lipid profile, malondialdehyde (MDA),
      superoxide dismutase (SOD), glutathione (GSH), glycosylated serum protein (GSP),
      and nitric oxide (NO). RESULTS: Diabetic rats treated with TFE or TTE had
      decreased concentration of FBG and GSP compared with the control group.
      Meanwhile, the levels of serum total cholesterol (TC), triglycerides (TG) and low
      density lipoprotein cholesterol (LDL-c) in the TFE or TTE treated diabetic rats
      were lower, and the high-density lipoprotein cholesterol (HDL-c) level was higher
      than in the control diabetic rats. Furthermore, the extracts treatment decreased
      the MDA and NO level, while increased SOD and GSH levels in diabetic rats.
      Histopathologic examination also showed that the extracts have protective effects
      on beta-cells in diabetic rats which are supported by the increase of SI.
      CONCLUSIONS: All these experimental results highlighted the hypoglycemic and
      hypolipidemic properties of the two extracts from Potentilla discolor Bunge on
      diabetes and its complications, possibly through a strong antioxidant activity
      and a protective action on beta-cells.

PMID- 20816942
TI  - Pregnane-X-receptor mediates the anti-inflammatory activities of rifaximin on
      detoxification pathways in intestinal epithelial cells.
AB  - The pregnane-X-receptor (PXR) is master gene overseeing detoxification of wide
      number of xenobiotics and is critical for maintenance of intestinal integrity.
      The intestinal expression of genes involved in cellular detoxification is down
      regulated in patients with inflammatory bowel diseases (IBD). Rifaximin is a non
      absorbable antibiotic endowed with a PXR agonistic activity. In the present study
      we have investigated whether rifaximin activates PXR in primary human colon
      epithelial cells and human colon biopsies and assessed whether this antibiotic
      antagonizes the effect of tumor necrosis factor (TNF)-alpha on expression of PXR
      and PXR-related genes. Present results demonstrate that primary colon epithelial
      cells express PXR and that their exposure to rifaximin induces the expression of
      genes involved in cellular detoxification. Exposure to TNFalpha reduces the
      expression of PXR mRNA as well as expression of its target genes. This inhibitory
      effect was prevented by that co-treatment with rifaximin. Knocking down the
      expression of PXR in colon epithelial cells by an anti-PXR siRNA, abrogated the
      counter-regulatory effects exerted by rifaximin on cell exposed to TNFalpha.
      Finally, ex vivo exposure of colon biopsies obtained from ulcerative colitis
      patients to rifaximin increased the expression of genes involved in xenobiotics
      metabolism. In aggregate, these data illustrate that rifaximin increases the
      expression of PXR and PXR-regulated genes involved in the metabolism and
      excretion of xenobiotics and antagonizes the effects of TNFalpha in intestinal
      epithelial cells and colon biopsies. These non-antibiotic effects of rifaximin
      could contribute to the maintenance of the intestinal barrier integrity against
      xenobiotics and products generated by luminal bacteria.

PMID- 20816943
TI  - High-value products from transgenic maize.
AB  - Maize (also known as corn) is a domesticated cereal grain that has been grown as
      food and animal feed for tens of thousands of years. It is currently the most
      widely grown crop in the world, and is used not only for food/feed but also to
      produce ethanol, industrial starches and oils. Maize is now at the beginning of a
      new agricultural revolution, where the grains are used as factories to synthesize
      high-value molecules. In this article we look at the diversity of high-value
      products from maize, recent technological advances in the field and the emerging
      regulatory framework that governs how transgenic maize plants and their products
      are grown, used and traded.

PMID- 20816944
TI  - Evidence that obesity and androgens have independent and opposing effects on
      gonadotropin production from puberty to maturity.
AB  - Optimal fat mass is necessary for normal gonadotropin levels in adults, and both
      undernutrition and overnutrition suppress gonadotropins: thus, the gonadotropin
      response to relative adipose mass is biphasic. Adult obesity is associated with
      blunted luteinizing hormone (LH) pulse amplitude that is partially attributable
      to increased LH clearance rate. Testosterone appears to have a biphasic effect on
      gonadotropin production in females. Moderate elevations of testosterone appear to
      stimulate LH production at both the hypothalamic and pituitary level, while very
      high levels of testosterone suppress LH. Thus, obesity per se appears to suppress
      gonadotropin production, and moderate hyperandrogenemia in women appears to
      stimulate LH. The ordinary hypergonadotropic hyperandrogenism of obese women
      appears to be an exception to this model because it is usually due to polycystic
      ovary syndrome (PCOS), a condition in which intrinsic functional ovarian
      hyperandrogenism and excess adiposity share a common origin that involves insulin
      resistant hyperinsulinemia. LH elevation seems to be secondary to
      hyperandrogenemia and is absent in the most obese cases. Overweight early
      pubertal girls have significant blunting of sleep-related LH production, which is
      the first hormonal change of puberty. The data are compatible with the
      possibility that excess adiposity may paradoxically subtly suppress hypothalamic
      pituitary-gonadal function in early puberty although it is known to contribute to
      the early onset of puberty.

PMID- 20816945
TI  - Impact of mutations in kisspeptin and neurokinin B signaling pathways on human
      reproduction.
AB  - The involvement of kisspeptin and neurokinin in B pathways in the reproductive
      axis was first suspected by linkage analysis in consanguineous families with
      isolated hypogonadotropic hypogonadism (IHH). Since then, several loss-of
      function mutations affecting the kisspeptin receptor and neurokinin B and its
      receptor were associated with sporadic and familial IHH without olfactory
      abnormalities or other associated developmental alterations. Clinical
      manifestations were indistinguishable in individuals with mutations affecting
      these pathways. Micropenis and cryptorchidism were common findings among male
      patients. Response to acute GnRH stimulation varied from blunted to normal, and
      many affected males and females were successfully treated for infertility with
      either exogenous gonadotropins or long term pulsatile GnRH infusion. More
      recently, rare activating mutations of the kisspeptin and its receptor were
      identified in children with idiopathic central precocious puberty, supporting the
      crucial role of this system in the human pubertal onset. Kisspeptin is a potent
      excitatory regulator of the GnRH secretion, whereas the role of neurokinin B in
      the neuroendocrine control of the reproductive axis is still poorly understood.
      Interestingly, kisspeptin and neurokinin B are coexpressed in the arcuate nucleus
      in the mammalian hypothalamus, suggesting that these systems are closely related
      and potential partners of the regulation of the reproductive axis.

PMID- 20816946
TI  - MiRNA-451 plays a role as tumor suppressor in human glioma cells.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene
      expression at the post-transcriptional and/or translational level by binding
      loosely complimentary sequences in the 3'untranslated regions (UTRs) of target
      mRNAs. Increased expressions of several miRNAs, specifically hsa-miR-21, have
      been reported to modulate glioma development. Here we report downregulation of
      miR-451 in A172, LN229 and U251 human glioblastoma cells. Increased expression of
      miR-451 by administration of miR-451 mimics oligonucleotides reversed the biology
      of each of the three cell lines, inhibiting cell growth, inducing G0/G1 phase
      arrest and increasing cell apoptosis. Further, treatment with miR-451 mimics
      oligonucleotides diminished the invasive capacity of these cells, as the number
      of cells invading through matrigel was significantly decreased. Akt1, CyclinD1,
      MMP-2, MMP-9 and Bcl-2 protein expression decreased, and p27 expression increased
      in a dose-dependent manner with miR-451 mimics oligonucleotides. Taken together,
      these studies reveal miR-451 impacts glioblastoma cell proliferation, invasion
      and apoptosis, perhaps via regulation of the PI3K/AKT signaling pathway. We
      propose an essential role for miR-451 as a tumor-suppressor of human glioma.

PMID- 20816947
TI  - Quantitative cytometry as a tool for toxicity assessment (27th annual workshop of
      the Scandinavian Society for Cell Toxicology).

PMID- 20816948
TI  - CA 15-3: uses and limitation as a biomarker for breast cancer.
AB  - CA 15-3 which detects soluble forms of MUC-1 protein is the most widely used
      serum marker in patients with breast cancer. Its main use is for monitoring
      therapy in patients with metastatic disease. In monitoring therapy in this
      setting, CA 15-3 should not be used alone but measured in conjunction with
      diagnostic imaging, clinical history and physical examination. CA 15-3 is
      particularly valuable for treatment monitoring in patients that have disease that
      cannot be evaluated using existing radiological procedures. CA 15-3 may also be
      used in the postoperative surveillance of asymptomatic women who have undergone
      surgery for invasive breast cancer. In this setting, serial determination can
      provide median lead-times of 5-6 months in the early detection of
      recurrent/metastatic breast cancer. It is unclear however, whether administering
      systemic therapy based on this lead-time improves patient outcome. Consequently,
      expert panels disagree on the utility of regularly measuring CA 15-3 in the
      postoperative surveillance of asymptomatic women following a diagnosis of breast
      cancer. The main limitation of CA 15-3 as a marker for breast cancer is that
      serum levels are rarely increased in patients with early or localized disease.

PMID- 20816949
TI  - Rapid determination of vitamin B2 (riboflavin) in plasma by HPLC.
AB  - BACKGROUND: Riboflavin (vitamin B2), as the exclusive source for the coenzymes
      flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) in humans, is a
      water-soluble vitamin critical for metabolism and energy production. In its
      coenzyme forms, riboflavin is involved in essential oxidation-reduction
      reactions. Deficiency leads to skin and mucosal disorders. Measurement of plasma
      riboflavin can be used to assess vitamin B2 status in at-risk individuals.
      METHODS: Proteins are removed from plasma by acid precipitation. An aliquot of
      the resulting supernatant is analyzed by reversed-phase HPLC. Impurities are
      separated from riboflavin isocratically and the target material is detected
      fluorometrically (excitation 450 nm; emission 520 nm). RESULTS: The method was
      validated for linearity, limit of quantification, accuracy, precision, and
      interference. The method was accurate and correlated well (R2 = 0.993) to
      expected concentrations of spiked pooled plasma samples. Imprecision was < 10%.
      Riboflavin concentrations were determined in samples obtained from self-reported
      healthy adults who were not taking vitamin supplements. The reference interval
      established by nonparametric analysis was 6.7-50.1 nmol/l. CONCLUSIONS: This HPLC
      method allows separation and measurement of riboflavin in plasma in 7 min.
      Results from the assay may be used for clinical diagnosis of deficiency and to
      monitor therapeutic vitamin supplementation regimes.

PMID- 20816950
TI  - The influence of influenza A (H1N1) virus on creatinine and cystatin C.
AB  - BACKGROUND: In March 2009, the novel 2009 influenza A (H1N1) virus was first
      reported in the southwestern USA and Mexico. It rapidly spread to China and
      worldwide. We investigated possible kidney injury in patients with the 2009
      influenza A (H1N1) virus in China. METHODS: This study was a retrospective cohort
      investigation of the potential renal injury in patients of influenza. One hundred
      and seventy-two patients confirmed to have the 2009 influenza A (H1N1) virus but
      who had different levels of severity (non-severe, severe, and critically severe)
      and 21 cases who were influenza A (H1N1)-negative but who had an influenza-like
      illness were investigated. Blood samples were obtained for the measurement of
      creatinine (Cr) and cystatin C (Cy-C). RESULTS: The influenza A (H1N1) virus
      caused more illness in middle-aged people in all groups. The patients in the non
      severe group were younger than those in the severe group (p<0.05) and the non
      influenza A (H1N1) group (p<0.01). Four subjects in the critically severe group
      died (3 due to respiratory failure, 1 heart injury). A significant difference in
      the levels of Cr and Cy-C between the groups was not observed (p>0.05).
      CONCLUSION: The 2009 influenza A (H1N1) virus did not cause severe kidney injury
      in the acute phase in adult patients.

PMID- 20816951
TI  - Mechanisms of LDL oxidation.
AB  - BACKGROUNDS: Many lines of evidence suggest that oxidized low-density lipoprotein
      (LDL) is implicated in the pathogenesis of atherosclerotic vascular diseases.
      This review summarizes a diversity of mechanisms proposed for LDL oxidation
      serving for the so-called "LDL oxidation hypothesis of atherogenesis". METHODS
      AND RESULTS: We investigated the literature and our research results related to
      mechanisms of LDL oxidation and its atherogenesis. LDL oxidation is catalyzed by
      transition metal ions and several free radicals, and LDL is also oxidized by some
      oxidizing enzymes. In this way, LDL can be converted to a form that is recognized
      specifically by and with high affinity to macrophage scavenger receptors, leading
      to foam cell formation, the defining characteristic of fatty streak lesions.
      CONCLUSIONS: Several pathways are involved in the promotion of LDL oxidation in
      vitro and in vivo, but it would appear that the physiologically relevant
      mechanisms of LDL oxidation are still imperfectly understood. The underlying
      mechanisms of LDL oxidation must be further explored to reveal appropriate ways
      for the diagnosis and treatment of atherosclerosis and its relevant diseases.

PMID- 20816952
TI  - Misinterpretation of results in medico-legal cases due to microdeletion in the Y
      chromosome.
AB  - In an alleged rape case, for one male suspect, XX genotype and deletion at four Y
      STR loci was noticed. The expressions of 18 Y-linked genes were studied to
      measure the extent of deletion. No expressions at two loci were observed that
      might have caused the misinterpretations in forensic casework.

PMID- 20816953
TI  - Chemosensitization of human leukemia K562 cells to taxol by a Vanadium-salen
      complex.
AB  - Vanadium complexes are a heterogeneous class of compounds exhibiting interesting
      biological properties. Herein, we report the effect of a vanadium-salen complex
      (VO-salen) on proliferative behavior of K562 cell line. The results revealed that
      VO-salen at 6-32 MUM inhibited K562 proliferation with no distinct alteration in
      cell morphology, extent of apoptosis and/or differentiation. Our results
      indicated that VO-salen complex has just a cytostatic effect and capable of
      arresting the affected cells in G2/M phase of cell cycle. In addition, we
      evaluated the combined effects of VO-salen complex and taxol. The cell cycle
      analyses showed that VO-salen complex enhanced taxol-induced G2/M arrest and also
      increased taxol-induced apoptosis through a decrease in the ratio of Bcl-2/Bax
      which might account for the decrease in the apoptosis threshold among the
      affected cells. These findings support that combination of VO-salen, as a
      chemosensitizer, and taxol might constitute an affective new strategy for
      leukemia therapy.

PMID- 20816954
TI  - Validated models for predicting skin penetration from different vehicles.
AB  - The permeability of a penetrant though skin is controlled by the properties of
      the penetrants and the mixture components, which in turn relates to the molecular
      structures. Despite the well-investigated models for compound permeation through
      skin, the effect of vehicles and mixture components has not received much
      attention. The aim of this Quantitative Structure Activity Relationship (QSAR)
      study was to develop a statistically validated model for the prediction of skin
      permeability coefficients of compounds dissolved in different vehicles.
      Furthermore, the model can help with the elucidation of the mechanisms involved
      in the permeation process. With this goal in mind, the skin permeability of four
      different penetrants each blended in 24 different solvent mixtures were
      determined from diffusion cell studies using porcine skin. The resulting 96 kp
      values were combined with a previous dataset of 288 kp data for QSAR analysis.
      Stepwise regression analysis was used for the selection of the most significant
      molecular descriptors and development of several regression models. The selected
      QSAR employed two penetrant descriptors of Wiener topological index and total
      lipole moment, boiling point of the solvent and the difference between the
      melting point of the penetrant and the melting point of the solvent. The QSAR was
      validated internally, using a leave-many-out procedure, giving a mean absolute
      error of 0.454 for the logkp value of the test set.

PMID- 20816955
TI  - Teladorsagia circumcincta: the transcriptomic response of a multi-drug-resistant
      isolate to ivermectin exposure in vitro.
AB  - The emergence and spread of anthelmintic resistance in parasitic nematodes is a
      serious threat to the sustainability of the livestock industry. Resistance has a
      genetic component but the underlying mechanisms and the means by which resistant
      parasites survive anthelmintic treatment are still poorly understood.
      Differential gene expression may be implicated, especially in multi-drug
      resistant parasites. In this study, we investigated the transcriptomic response
      of a triple drug-resistant isolate of Teladorsagia circumcincta to ivermectin
      exposure in vitro, using Roche 454 sequencing. The study generated ~100,000 new
      EST sequences, ~50,000 each from the ivermectin-exposed and -unexposed pools of
      parasites. Bioinformatic analysis of the expression profiles revealed
      statistically significant differences in the mean expression levels of four KEGG
      orthologous groups, namely 'translation', 'amino acid metabolism', 'carbohydrate
      metabolism' and 'xenobiotic degradation and metabolism'. Notably, candidate
      resistance genes such as p-glycoproteins and cytochrome P450s were poorly
      represented in both datasets. Clusters of sequences, containing both exposed and
      unexposed ESTs, also revealed statistically significant differences. Four
      clusters were identified as cytochrome c oxidase subunits, two of these clusters
      had a statistically significant increase in the number of exposed ESTs compared
      to unexposed ESTs. Four clusters were identified as vitellogenin; three of these
      clusters had a statistically significant decrease in number of exposed ESTs
      compared to unexposed ESTs.

PMID- 20816956
TI  - Synthesis, characterization and assessment of suitability of trehalose fatty acid
      esters as alternatives for polysorbates in protein formulation.
AB  - Nonionic polyethylene glycol-derived surfactants are today's choice as
      surfactants in protein formulations. Different groups discovered that although
      surface-induced stresses are reduced by these excipients, the long-term stability
      of different proteins decreased due to polyethylene glycol-related induction of
      oxidation processes under static storage conditions. In this paper, the potential
      of polyoxyethylene-free surfactants for protein formulation was evaluated. Three
      different sugar-based surfactants, 6-O-monocaprinoyl-alpha,alpha-trehalose, 6-O
      monolauroyl-alpha,alpha-trehalose and 6-O-monopalmitoyl-alpha,alpha-trehalose,
      were synthesized in four reaction steps. These substances lack polyethylene
      glycol residues and can be produced from renewable resources. The chemical and
      physical properties of these three surfactants were investigated and compared
      with polysorbate 20 and 80. 6-O-monopalmitoyl-alpha,alpha-trehalose was insoluble
      in water at room temperature and was hence excluded from some of the further
      tests. The critical micellar concentration of all surfactants is in a comparable
      range of approximately 0.001-0.01% (m/V). The sugar-based surfactants showed
      slightly higher hemolytic activity than the polysorbate references. The
      surfactants with shorter chain length proved to be comparable to polysorbates in
      regard to physicochemical properties. Finally for human growth hormone, the
      protein-stabilizing properties against shaking-induced stress were tested and
      compared to polysorbate-containing formulations. Whereas in the absence of
      surfactant, dramatic monomer loss and aggregate formation occurred, it was found
      that 100% monomer content was maintained when 0.1% (m/V) 6-O-monocaprinoyl
      alpha,alpha-trehalose or 6-O-monolauroyl-alpha,alpha-trehalose was added to the
      formulation. Polysorbate 80 at a concentration of 0.1% (m/V) also significantly
      stabilized the protein. Lower amounts of surfactants result in only partial
      stabilization. Furthermore, adsorption of human growth hormone to the container
      surface is reduced in the presence of the surfactants. Thus, the new sugar-based
      surfactants offer a promising alternative and have potential for application in
      protein formulations.

PMID- 20816957
TI  - Vancomycin release from poly(D,L-lactic acid) spray-coated hydroxyapatite fibers.
AB  - The influence of the poly(D,L-lactic acid) (PDLLA) coating thickness on the in
      vitro vancomycin release from a hydroxyapatite (HA) carrier was studied.
      Microporous HA fibers with a porosity of 51 v% and an average pore diameter of
      1.0 MUm were fabricated by a diffusion-induced phase separation technique. They
      were loaded with 38 mg vancomycin hydrochloride (VH)/gHA, and their cylindrical
      shape enabled the application of the spray coating technique for the deposition
      of uniform PDLLA coating thicknesses, varying from 6.5 MUm to 28 MUm. The
      resulting in vitro VH release varied from a complete release within 14 days for
      6.5 MUm coatings to a release of 23% after 28 days for 28 MUm coatings. It was
      clear that the VH release rate from a HA fiber can be adjusted by varying the
      PDLLA coating thickness. Microbiological tests of these fibers against a
      methicillin-resistant Staphylococcus aureus (MRSA) isolate pointed to the
      importance of the initial burst release and confirmed that the released
      antibiotics had the potential to interfere with S. aureus biofilm formation.

PMID- 20816958
TI  - Chitosan hollow nanospheres fabricated from biodegradable poly-D,L-lactide
      poly(ethylene glycol) nanoparticle templates.
AB  - Biodegradable chitosan hollow nanospheres were fabricated by employing uniform
      poly-D,L-lactide-poly(ethylene glycol) (PELA) nanoparticles as templates.
      Chitosan was adsorbed onto the surface of PELA nanoparticle templates through the
      electrostatic interaction between the sulphuric acid groups from sodium dodecyl
      sulfate (SDS) on the templates and the amino groups of the chitosan.
      Subsequently, the core-coated structure of chitosan-PELA nanospheres was obtained
      with the adsorbed chitosan layer being further crosslinked with glutaraldehyde.
      After the removal of the templates, PELA cores, chitosan hollow nanospheres were
      achieved. The mean size and size distribution of these nanospheres were measured
      with dynamic light scattering. The hollow structure was identified by
      transmission electron microscopy, atomic force microscopy and laser confocal
      scanning microscope. The antitumor drug model, adriamycin hydrochloride, was
      adsorbed on/into the chitosan hollow nanospheres. The drug release behaviors were
      investigated in phosphate buffered solution (PBS) at pH 7.4 and acetate buffered
      solution (ABS) at pH 4.5, respectively, at 37 degrees C, and in vitro tumor cell
      growth inhibition assay was also evaluated. The biodegradable hollow nanospheres
      possess great potential applications in nanomedicine.

PMID- 20816959
TI  - Temozolomide/PLGA microparticles plus vatalanib inhibits tumor growth and
      angiogenesis in an orthotopic glioma model.
AB  - Temozolomide (TM) has anti-tumor activity in patients with malignant glioma.
      Implantable poly (D,L-lactide-co-glycolide) (PLGA) microparticles of TM (TM-MS)
      have been developed, enhancing the cytotoxicity of TM to Glioma C6 cells.
      Vatalanib, as anti-angiogenic agent, has also shown anti-tumor activity with
      malignant gliomas. We examined the combined effects of TM-MS and vatalanib in a
      rat orthotopic glioma model and found TM-MS offered a greater tumor inhibition
      than TM, and combination treatment with both of them improved the survival time
      versus single agent therapy. The combination treatment also demonstrated an
      inhibition to rat glioma tumors, a significant decrease in cell proliferation, an
      increase in apoptosis, and a lower microvessel density within the glioma tumors.
      The results suggest that TM-MS can more effectively inhibit tumor than TM, and
      combination treatment with TM-MS and vatalanib inhibits tumor growth and
      angiogenesis and may prove to be a promising therapy for malignant gliomas.

PMID- 20816960
TI  - Biochemical characterization of the RNA-hydrolytic activity of a pumpkin 2S
      albumin.
AB  - A pumpkin 2S albumin with ribonuclease (RNase) activity was purified from pumpkin
      seeds (Cucurbita sp.) by liquid chromatographic techniques. It manifested potent
      RNase activity toward baker's yeast RNA and calf liver RNA, and some
      polyhomoribonucleotides, including poly(A), poly(U) and poly(C) but not poly(G).
      Moreover, it was able to hydrolyze total RNA of both animal and plant origins.
      Ions such as Na(+), Mg(2+), Ca(2+), and Zn(2+) inhibited its RNase activity.
      Since RNase activity has not been previously reported in 2S albumins, this work
      may shed further light on the biological importance of this group of proteins.

PMID- 20816961
TI  - MicroRNA-24 targeting RNA-binding protein DND1 in tongue squamous cell carcinoma.
AB  - Deregulations of microRNA have been frequently observed in tongue squamous cell
      carcinoma (TSCC), but their roles in tumorigenesis are not entirely clear. Here,
      we reported the up-regulation of miR-24 in TSCC. MiR-24 up-regulation reduced the
      expression of RNA-binding protein dead end 1 (DND1). Knockdown of miR-24 led to
      enhanced expression of DND1. The direct targeting of miR-24 to the DND1 mRNA was
      predicted bioinformatically and confirmed by luciferase reporter gene assays.
      Furthermore, the miR-24-mediated change in DND1 expression suppressed the
      expression of cyclin-dependent kinase inhibitor 1B (CDKN1B), and also led to
      enhanced proliferation and reduced apoptosis in TSCC cells.

PMID- 20816962
TI  - A new hypothesis on the simultaneous direct and indirect proton pump mechanisms
      in NADH-quinone oxidoreductase (complex I).
AB  - Recently, Sazanov's group reported the X-ray structure of whole complex I
      [Nature, 465, 441 (2010)], which presented a strong clue for a "piston-like"
      structure as a key element in an "indirect" proton pump. We have studied the NuoL
      subunit which has a high sequence similarity to Na(+)/H(+) antiporters, as do the
      NuoM and N subunits. We constructed 27 site-directed NuoL mutants. Our data
      suggest that the H(+)/e(-) stoichiometry seems to have decreased from (4H(+)/2e(
      )) in the wild-type to approximately (3H(+)/2e(-)) in NuoL mutants. We propose a
      revised hypothesis that each of the "direct" and the "indirect" proton pumps
      transports 2H(+) per 2e(-).

PMID- 20816963
TI  - Development of an image analysis screen for estrogen receptor alpha (ERalpha)
      ligands through measurement of nuclear translocation dynamics.
AB  - We have developed a robust high-content assay to screen for novel estrogen
      receptor alpha (ERalpha) agonists and antagonists by quantitation of cytoplasmic
      to nuclear translocation of an estrogen receptor chimera in 384-well plates. The
      screen utilizes a green fluorescent protein tagged-glucocorticoid/estrogen
      receptor (GFP-GRER) chimera which consisted of the N-terminus of the
      glucocorticoid receptor fused to the human ER ligand binding domain. The GFP-GRER
      exhibited cytoplasmic localization in the absence of ERalpha ligands, and
      translocated to the nucleus in response to stimulation with ERalpha agonists or
      antagonists. The BD Pathway 435 imaging system was used for image acquisition,
      analysis of translocation dynamics, and cytotoxicity measurements. The assay was
      validated with known ERalpha agonists and antagonists, and the Library of
      Pharmacologically Active Compounds (LOPAC 1280). Additionally, screening of crude
      natural product extracts demonstrated the robustness of the assay, and the
      ability to quantitate the effects of toxicity on nuclear translocation dynamics.
      The GFP-GRER nuclear translocation assay was very robust, with z' values >0.7,
      CVs <5%, and has been validated with known ER ligands, and inclusion of
      cytotoxicity filters will facilitate screening of natural product extracts. This
      assay has been developed for future primary screening of synthetic, pure natural
      products, and natural product extracts libraries available at the National Cancer
      Institute at Frederick.

PMID- 20816964
TI  - Extended paced mating tests induces conditioned place preference without
      affecting sexual arousal.
AB  - One way to evaluate sexual arousal is by measuring approach behavior to sexual
      incentive stimuli. In our case we measure approach behavior to an originally non
      preferred compartment which is associated with the physiological state induced by
      mating. This change of preference indicative of a positive affective (reward)
      state can be evaluated by conditioned place preference (CPP). We have shown that
      the CPP induced by paced mating is mediated by opioids. The administration of
      opioids also induces a reward state. The present study was designed to compare
      the rewarding properties of paced mating and a morphine injection. One group of
      females was allowed to pace the sexual interaction before being placed in the non
      preferred compartment. In alternate sessions they received a morphine injection
      before being placed in the preferred compartment. In another group of females,
      the treatments were reversed. Only the females placed in the originally non
      preferred compartment after paced mating changed their original preference,
      suggesting that paced mating induces a positive affective, reward, state of
      higher intensity than a morphine injection of 1mg/kg. In a second experiment we
      determined if females allowed to pace the sexual interaction for 1h would still
      developed CPP. No change in preference was observed in the females that mated for
      1h without pacing the sexual interaction. On the other hand, females that
      received between 10 and 15 paced intromissions as well as females that paced the
      sexual interaction for 1h developed a clear CPP. The second experiment
      demonstrated that pacing is rewarding even in an extended mating session in which
      the females received around 25 intromissions and several ejaculations. These
      results further demonstrate the biological relevance associated with the ability
      of the female to space coital stimulation received during mating. This positive
      affective state will contribute to increase sexual arousal the next time a rat
      finds an appropriate mate.

PMID- 20816966
TI  - Pre-experience of social exclusion suppresses cortisol response to psychosocial
      stress in women but not in men.
AB  - Lack of social support and social exclusion is associated with adverse effects
      for mental and physical health. Additionally, women appear to be more vulnerable
      to social triggers of health disturbances. The hypothalamus-pituitary
      adrenocortical-axis (HPA axis) might play a key role in this context as it has
      been shown both to relate to psychosocial conditions and health outcomes and to
      respond differentially depending on gender. In a previous experiment we found no
      effects of exclusion alone (operationalized via Cyberball) on cortisol secretion.
      Here we examine the effects of a social exclusion pre-experience on psychological
      and cortisol responses to a public speaking stressor. Subjects (33 m, 34 f) were
      randomly assigned to social exclusion (SE) or one of two control conditions
      (exclusion attributed to technical default (TD) and social inclusion (SI)).
      Afterwards salivary cortisol and psychological responses to a public speaking
      paradigm were assessed. Exclusion pre-treatment does not affect psychological
      responses to public speaking stress though with respect to cortisol significant.
      Cyberball by gender and Cyberball by gender by time interactions are found. SE
      women show a blunted cortisol stress response to public speaking while cortisol
      responses of SE-men fall between SI-men and TD-men. Pre-experience of social
      exclusion leads to a blunted cortisol response to stress in women but not in men.
      This factor might contribute to the higher vulnerability to social triggers of
      health disturbances observed in women.

PMID- 20816965
TI  - Reversible histone methylation regulates brain gene expression and behavior.
AB  - Epigenetic chromatin remodeling, including reversible histone methylation,
      regulates gene transcription in brain development and synaptic plasticity.
      Aberrant chromatin modifications due to mutant chromatin enzymes or chemical
      exposures have been associated with neurological or psychiatric disorders such as
      mental retardation, schizophrenia, depression, and drug addiction. Some chromatin
      enzymes, such as histone demethylases JARID1C and UTX, are coded by X-linked
      genes which are not X-inactivated in females. The higher expression of JARID1C
      and UTX in females could contribute to sex differences in brain development and
      behavior.

PMID- 20816967
TI  - Impact of estrogen receptor alpha and beta agonists on delayed alternation in
      middle-aged rats.
AB  - Estrogens act in the adult brain to modulate cognition, enhancing performance on
      some learning tests and impairing performance on others. Our previous research
      has revealed an impairing effect of chronic 17beta-estradiol treatment in young
      and aged rats on a prefrontally-mediated working memory task, delayed spatial
      alternation (DSA). Little is known about the mechanisms of these impairing
      effects. The current study examined the effects of selective estrogen receptor
      (ER) alpha or ERbeta activation on DSA performance in middle-aged female rats.
      Ovariectomized 12 month old Long-Evans (LE) rats were treated by subcutaneous
      injection with the ERalpha agonist propyl pyrazole triol (PPT) or the ERbeta
      agonist diarylpropionitrile (DPN) at 0.02, 0.08, or 0.20mg/kg/day, or with oil
      vehicle and tested on an operant variable delay DSA task. A 17beta-estradiol
      group (10% in cholesterol) was included as a positive control group. We
      replicated our previous finding of a 17beta-estradiol induced deficit on DSA
      performance and this effect was paralleled by low dose (0.02mg/kg/day) DPN
      treatment. Higher doses of DPN failed to produce a significant change in
      performance. The highest dose of PPT (0.20mg/kg/day) also impaired performance,
      but this effect was subtle and limited to the longest delay during the final
      block of testing. These data confirm our earlier findings that chronic 17beta
      estradiol treatment has an impairing effect on the DSA task, and suggest that
      ERbeta activation may underlie the deficit.

PMID- 20816969
TI  - On the intricate relationship between sexual motivation and arousal.
AB  - Sexual motivation and sexual arousal are widely used concepts. While there seem
      to be considerable agreement as to the meaning of sexual motivation, there is
      certain confusion about the exact meaning of sexual arousal. Some use it as a
      synonym to sexual motivation and others make it equivalent to erection or vaginal
      lubrication. An unresolved question is the relationship between sexual arousal
      and general arousal as well as that between arousal and motivation. I present
      arguments for the view that arousal refers to the general state of alertness of
      the organism. Consequently, there is no such thing as a specific sexual arousal.
      I suggest that this term should be abandoned, or if that is not feasible, to make
      it a synonym to enhanced genital blood flow. The notion of a subjective sexual
      arousal, some kind of vaguely described mental state, seems to lack all
      explanatory value. I then show that general arousal is an important determinant
      of sexual motivation, and that the execution of copulatory acts leads to
      increased general arousal. This increase leads to enhanced sexual motivation,
      making the activation of sexual reflexes requiring high levels of motivation
      possible. Examples of such reflexes may be ejaculation in males of many species,
      and perhaps the psychic state of orgasm in women.

PMID- 20816968
TI  - Female sexual arousal in amphibians.
AB  - Rather than being a static, species specific trait, reproductive behavior in
      female amphibians is variable within an individual during the breeding season
      when females are capable of reproductive activity. Changes in receptivity
      coincide with changes in circulating estrogen. Estrogen is highest at the point
      when females are ready to choose a male and lay eggs. At this time female
      receptivity (her probability of responding to a male vocal signal) is highest and
      her selectivity among conspecific calls (measured by her probability of
      responding to a degraded or otherwise usually unattractive male signal) is
      lowest. These changes occur even though females retain the ability to
      discriminate different acoustic characteristics of various conspecific calls.
      After releasing her eggs, female amphibians quickly become less receptive and
      more choosy in terms of their responses to male sexual advertisement signals.
      Male vocal signals stimulate both behavior and estrogen changes in amphibian
      females making mating more probable. The changes in female reproductive behavior
      are the same as those generally accepted as indicative of a change in female
      sexual arousal leading to copulation. They are situationally triggered, gated by
      interactions with males, and decline with the consummation of sexual reproduction
      with a chosen male. The changes can be triggered by either internal physiological
      state or by the presence of stimuli presented by males, and the same stimuli
      change both behavior and physiological (endocrine) state in such a way as to make
      acceptance of a male more likely. Thus amphibian females demonstrate many of the
      same general characteristics of changing female sexual state that in mammals
      indicate sexual arousal.

PMID- 20816970
TI  - Relationships among hormones, brain and motivated behaviors in lizards.
AB  - Lizards provide a rich opportunity for investigating the mechanisms associated
      with arousal and the display of motivated behaviors. They exhibit diverse mating
      strategies and modes of conspecific communication. This review focuses on anole
      lizards, of which green anoles (Anolis carolinensis) have been most extensively
      studied. Research from other species is discussed in that context. By considering
      mechanisms collectively, we can begin to piece together neural and endocrine
      factors mediating the stimulation of sexual and aggressive behaviors in this
      group of vertebrates.

PMID- 20816971
TI  - Single-cell analysis of sodium channel expression in dorsal root ganglion
      neurons.
AB  - Sensory neurons of the dorsal root ganglia (DRG) express multiple voltage-gated
      sodium (Na) channels that substantially differ in gating kinetics and
      pharmacology. Small-diameter (<25 MUm) neurons isolated from the rat DRG express
      a combination of fast tetrodotoxin-sensitive (TTX-S) and slow TTX-resistant (TTX
      R) Na currents while large-diameter neurons (>30 MUm) predominately express fast
      TTX-S Na current. Na channel expression was further investigated using single
      cell RT-PCR to measure the transcripts present in individually harvested DRG
      neurons. Consistent with cellular electrophysiology, the small neurons expressed
      transcripts encoding for both TTX-S (Nav1.1, Nav1.2, Nav1.6, and Nav1.7) and TTX
      R (Nav1.8 and Nav1.9) Na channels. Nav1.7, Nav1.8 and Nav1.9 were the predominant
      Na channels expressed in the small neurons. The large neurons highly expressed
      TTX-S isoforms (Nav1.1, Nav1.6, and Nav1.7) while TTX-R channels were present at
      comparatively low levels. A unique subpopulation of the large neurons was
      identified that expressed TTX-R Na current and high levels of Nav1.8 transcript.
      DRG neurons also displayed substantial differences in the expression of
      neurofilaments (NF200, peripherin) and Necl-1, a neuronal adhesion molecule
      involved in myelination. The preferential expression of NF200 and Necl-1 suggests
      that large-diameter neurons give rise to thick myelinated axons. Small-diameter
      neurons expressed peripherin, but reduced levels of NF200 and Necl-1, a pattern
      more consistent with thin unmyelinated axons. Single-cell analysis of Na channel
      transcripts indicates that TTX-S and TTX-R Na channels are differentially
      expressed in large myelinated (Nav1.1, Nav1.6, and Nav1.7) and small unmyelinated
      (Nav1.7, Nav1.8, and Nav1.9) sensory neurons.

PMID- 20816972
TI  - Differential subcellular distribution of endosomal compartments and the dopamine
      transporter in dopaminergic neurons.
AB  - Dopamine (DA) transporter (DAT) functions at the surface of dopaminergic neurons
      to clear extracellular DA. DAT surface levels are regulated by endocytosis.
      However, the endosome-lysosome system is not well characterized in dopaminergic
      neurons and the endocytic trafficking of endogenous DAT is poorly studied. Hence
      we analyzed the distribution of endocytic compartments and DAT localization in
      cultured rat embryonic and postnatal neurons using fluorescence microscopy. Early
      Rab5 and EEA.1 containing endosomes were mostly found in somatodendritic regions
      of neurons, whereas endosomes containing recycling markers were primarily found
      in axons. In axons, DAT was located mainly in recycling endosomes and plasma
      membrane whereas in cell bodies and dendrites DAT was detected in early, late and
      recycling endosomal compartments. Subcellular fractionation of adult rat striatal
      synaptosomes demonstrated that DAT is enriched in fractions containing plasma
      membrane and recycling endosomes. This pattern of DAT distribution was not
      altered upon activation of protein kinase C in postnatal DA neurons. Altogether,
      our data suggest that axonal DAT mainly shuttles between the plasma membrane and
      recycling endosomes, whereas in the somatodendritic region of neurons DAT
      traffics through all conventional endosomal pathways.

PMID- 20816974
TI  - Maturation of limbic corticostriatal activation and connectivity associated with
      developmental changes in temporal discounting.
AB  - Temporal discounting (TD) matures with age, alongside other markers of increased
      impulse control, and coherent, self-regulated behaviour. Discounting paradigms
      quantify the ability to refrain from preference of immediate rewards, in favour
      of delayed, larger rewards. As such, they measure temporal foresight and the
      ability to delay gratification, functions that develop slowly into adulthood. We
      investigated the neural maturation that accompanies the previously observed age
      related behavioural changes in discounting, from early adolescence into mid
      adulthood. We used functional magnetic resonance imaging of a hypothetical
      discounting task with monetary rewards delayed in the week to year range. We show
      that age-related reductions in choice impulsivity were associated with changes in
      activation in ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex
      (ACC), ventral striatum (VS), insula, inferior temporal gyrus, and posterior
      parietal cortex. Limbic frontostriatal activation changes were specifically
      associated with age-dependent reductions in impulsive choice, as part of a more
      extensive network of brain areas showing age-related changes in activation,
      including dorsolateral PFC, inferior parietal cortex, and subcortical areas. The
      maturational pattern of functional connectivity included strengthening in
      activation coupling between ventromedial and dorsolateral PFC, parietal and
      insular cortices during selection of delayed alternatives, and between vmPFC and
      VS during selection of immediate alternatives. We conclude that maturational
      mechanisms within limbic frontostriatal circuitry underlie the observed post
      pubertal reductions in impulsive choice with increasing age, and that this effect
      is dependent on increased activation coherence within a network of areas
      associated with discounting behaviour and inter-temporal decision-making.

PMID- 20816973
TI  - Using flow cytometry to screen patients for X-linked lymphoproliferative disease
      due to SAP deficiency and XIAP deficiency.
AB  - X-linked lymphoproliferative disease is a rare congenital immunodeficiency that
      is most often caused by mutations in SH2D1A, the gene encoding signaling
      lymphocyte activation molecule (SLAM)-associated protein (SAP). XLP caused by SAP
      deficiency is most often characterized by fulminant mononucleosis/EBV- associated
      hemophagocytic lymphohistiocytosis (HLH), lymphoma, and dysgammaglobulinemia. XLP
      has also been found to be caused by mutations in BIRC4, the gene encoding X
      linked inhibitor of apoptosis (XIAP). Patients with XIAP deficiency often present
      with HLH or recurrent HLH, which may or may not be associated with EBV. XLP is
      prematurely lethal in the majority of cases. While genetic sequencing can provide
      a genetic diagnosis of XLP, a more rapid means of diagnosis of XLP is desirable.
      Rapid diagnosis is especially important in the setting of HLH, as this may hasten
      the initiation of life-saving medical treatments and expedite preparations for
      allogeneic hematopoietic cell transplantation (HCT). Flow cytometry offers a
      means to quickly screen patients for XLP. Flow cytometry can be used to measure
      lymphocyte SAP or XIAP protein expression, and can also be used to observe
      lymphocyte phenotypes and functional defects that are unique to XLP. This review
      will give a brief overview of the clinical manifestations and molecular basis of
      SAP deficiency and XIAP deficiency, and will focus on the use of flow cytometry
      for diagnosis of XLP.

PMID- 20816975
TI  - Ecdysone signaling and transcript signature in Drosophila cells resistant against
      methoxyfenozide.
AB  - Methoxyfenozide (RH-2485) is a non-steroidal ecdysteroid agonist with a
      dibenzoylhydrazine structure, representing a group used as novel biorational
      insecticides in the control of insect pests. Here we report on the selection of
      Drosophila melanogaster S2 cells for resistance to inhibition of cell
      proliferation by methoxyfenozide by ~ 1000-fold over 4 months. Cells were exposed
      to gradually increasing concentrations of methoxyfenozide and selected out based
      on the ecdysteroid-sensitive response for cell proliferation. In the resistant
      cells, the ecdysteroid receptor (EcR/USP) complex was no longer active in the
      presence of methoxyfenozide. But when resistant cells were relaxed from pressure
      in methoxyfenozide-free medium, induction of the reporter construct was observed.
      In parallel, EcR/USP functionality was also restored when resistant cells were
      rescued by a Drosophila EcR plasmid. However, it was striking that in the
      resistant cells the ecdysteroid-sensitive response for cell proliferation was not
      restored upon methoxyfenozide withdrawal, indicating permanent changes in the
      physiology of the cells during selection. To investigate changes in gene
      expression caused by inactivation of the EcR/USP complex in resistant cells,
      Drosophila oligo 14kv1 microarrays were used and probed with cDNAs from resistant
      cells in the presence and absence of ecdysone agonist on one hand and from
      unselected sensitive cells on the other hand. A selection of 324 differentially
      expressed genes was assigned covering diverse functions as transport, enzyme
      activity, cytoskeleton organization, cell cycle machinery,
      transcription/translation and ecdysteroid signaling. Besides the identification
      of (primary and secondary) target genes of the EcR/USP signaling pathway, this
      analysis also allows to gain insights into the mechanism of resistance and on the
      crosstalk between ecdysteroid signaling and cell proliferation-linked processes.

PMID- 20816976
TI  - Attachment ability of the codling moth Cydia pomonella L. to rough substrates.
AB  - Host plant surfaces of the codling moth, Cydia pomonella L. (Lepidoptera,
      Tortricidae), vary in microtopography, which can affect its attachment,
      locomotion, and oviposition behaviour. This study was performed to investigate
      the effect of surface roughness on the attachment ability of adult insects. Using
      a centrifugal force device, friction forces of both sexes were assessed on six
      epoxy resin substrates differing only in the dimensions of their surface
      asperities, ranging from 0 MUm to 12 MUm. Surface topography significantly
      affected friction forces. Maximal force was measured on the smooth substrate
      whereas minimal force was assessed on microrough substrates with 0.3 MUm and 1.0
      MUm size of asperities. On the remaining rough substrates, friction forces were
      significantly higher but still lower than on the smooth substrate. Both sexes
      generated similar forces on the same substrate, in spite of the considerable
      difference in their body mass. Thus, it is expected that both sexes can attach
      effectively to differently structured plant substrates in their habitat. However,
      since smooth surfaces have been reported previously to be the most favorable
      substrates for ovipositing females of C. pomonella, it is possible that they use
      their attachment system to sense the substrate texture and prefer those
      substrates to which their arolia attach the best.

PMID- 20816977
TI  - Plumage patterns are good indicators of taxonomic diversity, but not of
      phylogenetic affinities, in Australian grasswrens Amytornis (Aves: Maluridae).
AB  - The grasswrens (Maluridae: Amytornis) are elusive songbirds from the arid zones
      of Australia. Although some other Australian bird genera are also largely
      restricted to arid regions, none show the level of localized taxonomic diversity
      seen in Amytornis. Furthermore, their cryptic plumage patterns provide excellent
      camouflage but make it difficult to determine whether shared patterns reflect
      phylogenetic relationships or adaptations to similar terrain. To resolve the
      systematics and patterns of ecological diversification within Amytornis, we here
      present the results of a phylogenetic analysis of mitochondrial and nuclear multi
      locus data for all recognized species and most subspecies, using traditional
      concatenation-based methods as well as a coalescent-based species-tree approach.
      Phylogenetic patterns retrieved by the species-tree approach were highly
      congruent with traditional methods, although branch support was generally higher
      in concatenation-based analysis, suggesting that species-tree methods may furnish
      more conservative results. In terms of identifying taxonomic diversity there was
      good concordance between plumage-based assessments and DNA distances. The same
      concordance was not found when comparing plumage-based and DNA-based predictions
      of phylogenetic relationships. Four primary lineages were identified: (a)
      barbatus; (b) merrotsyi; (c) the textilis complex, purnelli, ballarae, goyderi
      and housei; and (d) woodwardi, dorotheae, and the striatus complex. There was no
      robust resolution of relationships between lineages. It appears that in
      Amytornis, plumage differentiation between discrete populations is taxonomically
      significant, and not greatly influenced by ecophenotypic variation. However, at
      the deeper phylogenetic level, similar suites of plumage characters may be
      phylogenetically uninformative because of homoplasy. The study reveals higher
      levels of taxonomic diversity in Amytornis than previously recognized, with many
      taxa being highly localized. Such extensive short range endemism is mainly
      encountered in poorly-dispersing invertebrates and is unique in Australian birds.
      The identification here of the additional restricted range taxa has important
      conservation implications.

PMID- 20816978
TI  - Cyst-like lesions of the knee joint and their relation to incident knee pain and
      development of radiographic osteoarthritis: the MOST study.
AB  - OBJECTIVE: To determine whether intra- and periarticular cyst-like lesions of the
      knee are associated with incident knee pain and incident radiographic knee
      osteoarthritis (OA). DESIGN: The Multicenter Osteoarthritis (MOST) Study is a
      cohort of individuals who have or are at high risk for knee OA. Using a nested
      case-control study design, we investigated the associations of cyst-like lesions
      (Baker's, meniscal and proximal tibiofibular joint (PTFJ) cysts, and prepatellar
      and anserine bursitides) with (1) incident pain at 15- or 30-month follow-up and
      (2) incident radiographic OA at 30-month follow-up. Baseline cyst-like lesions
      were scored semiquantitatively using the Whole Organ Magnetic Resonance Imaging
      Score (WORMS). Conditional logistic regression models were used to assess the
      relation between these lesions and the outcomes, adjusting for potential
      confounding factors (i.e., cartilage loss, meniscal damage, bone marrow lesions,
      synovitis and joint effusion, which were also scored using WORMS). RESULTS:
      Incident knee pain study included 157 cases and 336 controls. Prevalence of
      meniscal and PTFJ cysts in the case group was twice that in the control group [9
      (6%) vs 9 (3%) and 9 (6%) vs 10 (3%), respectively]. Incident radiographic OA
      study included 149 cases and 298 controls. Prevalence of grade 2 Baker's cysts
      and PTFJ cysts in the case group was approximately four times that in the control
      group [16(11%) vs 9 (3%) and 6 (4%) vs 3 (1%), respectively]. However, none of
      the cyst-like lesions was associated with incident pain or radiographic OA after
      fully adjusted logistic regression analyses and correction of P-values for
      multiple comparisons. CONCLUSION: None of the analyzed lesions was an independent
      predictor of incident knee pain or radiographic OA. Intra- and periarticular cyst
      like lesions are likely to be a secondary phenomenon seen in painful or OA
      affected knees, rather than a primary trigger for incident knee pain or
      radiographic OA.

PMID- 20816979
TI  - Comparison of BLOKS and WORMS scoring systems part I. Cross sectional comparison
      of methods to assess cartilage morphology, meniscal damage and bone marrow
      lesions on knee MRI: data from the osteoarthritis initiative.
AB  - OBJECTIVE: To compare two semiquantitative scoring systems for assessing the
      prevalence and severity of morphologic cartilage lesions, meniscal damage and
      bone marrow lesions (BMLs) from Magnetic Resonance Imagings (MRIs) of knees with
      osteoarthritis (OA). METHODS: From participants in the OA Initiative (OAI), a
      sample of 115 knees with radiographic OA at high risk of cartilage loss, were
      selected based on risk factors for progression. Knee MRIs were read separately
      using both Whole Organ MR Scoring (WORMS) and Boston-Leeds OA Knee Scoring
      (BLOKS), and a subset was fed back to readers for reliability. Baseline readings
      were used for comparison of the two methods for inter-reader reliability as well
      as agreement on presence/absence and severity of MRI features at both the
      compartment level and finer anatomical subregion levels. RESULTS: Both methods
      had high inter-reader agreement for all features studied (kappa for WORMS 0.69
      1.0 and for BLOKS 0.65-1.0). Although the methods agreed well on presence and
      severity of morphological cartilage lesions (inter-method kappas from 0.66 to
      0.95), BLOKS was more sensitive for full thickness defects. The two methods gave
      equivalent results for extent (kappa 0.74-0.80) and number (Spearman's Rho=0.85)
      of BMLs, and little extra information was obtained using the more complex BLOKS
      BML scoring. Similar results were also obtained for the common types of meniscal
      damage and extrusion (inter-method kappa 0.85-0.94), but the inclusion in BLOKS
      of meniscal signal abnormality and uncommon types of tear may be an advantage if
      these prove clinically meaningful. CONCLUSION: Both WORMS and BLOKS had high
      reliability. The two methods gave similar results in this sample for prevalence
      and severity of cartilage loss, BMLs and meniscal damage. Selecting between, or
      combining, the two methods should be based on factors such as reader effort,
      appropriateness for the goals of a study, and longitudinal performance.

PMID- 20816980
TI  - Dynamic knee loading is related to cartilage defects and tibial plateau bone area
      in medial knee osteoarthritis.
AB  - OBJECTIVE: To evaluate the relationship between dynamic mechanical loading, as
      indicated by external knee adduction moment (KAM) measures during walking, and
      measures of articular cartilage morphology and subchondral bone size in people
      with medial knee osteoarthritis (OA). DESIGN: 180 individuals with radiographic
      medial tibiofemoral OA participated. Peak KAM and KAM angular impulse were
      measured by walking gait analysis. Tibial cartilage volume and plateau bone area,
      and tibiofemoral cartilage defects were determined from magnetic resonance
      imaging using validated methods. RESULTS: Both peak KAM (coefficient=0.42, 95%
      confidence interval (CI) 0.04-0.79, P=0.03) and KAM impulse (coefficient=1.79,
      95% CI 0.80-2.78, P<0.001) were positively associated with the severity of medial
      tibiofemoral cartilage defects. KAM impulse was also associated with the
      prevalence of medial tibiofemoral cartilage defects (odds ratio 4.78, 95% CI 1.10
      20.76, P=0.04). Peak KAM (B=0.05, 95% CI 0.01-0.09, P=0.02) and KAM impulse
      (B=0.16, 95% CI 0.06-0.25, P=0.002) were positively associated with
      medial:lateral tibial plateau bone area, and KAM impulse was also associated with
      medial tibial plateau bone area (B=133.7, 95% CI 4.0-263.3, P=0.04). There was no
      significant association between KAM measures and tibial cartilage volume.
      CONCLUSION: Peak KAM and KAM impulse are associated with cartilage defects and
      subchondral bone area in patients with medial knee OA, suggesting that increased
      mechanical loading may play a role in the pathological changes in articular
      cartilage and subchondral bone that occur with medial knee OA.

PMID- 20816981
TI  - Circulating levels of IL-6 and TNF-alpha are associated with knee radiographic
      osteoarthritis and knee cartilage loss in older adults.
AB  - OBJECTIVE: The role of inflammation in osteoarthritis (OA) pathogenesis is
      unclear, and the associations between inflammatory cytokines and cartilage loss
      have not been reported. We determined the associations between serum levels of
      interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha), knee radiographic
      OA (ROA) and cartilage loss over 2.9 years in older adults. METHODS: A total of
      172 randomly selected subjects (mean 63 years, range 52-78, 47% female) were
      studied at baseline and approximately 3 (range 2.6-3.3) years later. IL-6 and TNF
      alpha were assessed by radioimmunoassay. T1-weighted fat-suppressed magnetic
      resonance imaging of the right knee was performed at baseline and follow-up to
      determine knee cartilage volume. Knee ROA of both knees was assessed at baseline.
      RESULTS: At baseline, quartiles of IL-6 and TNF-alpha were associated with
      increased prevalence of medial tibiofemoral joint space narrowing (OARSI grade >=
      1) in multivariate analyses [odds ratio (OR): 1.42 and 1.47 per quartile,
      respectively, both P<0.05]. Longitudinally, baseline IL-6 predicted loss of both
      medial and lateral tibial cartilage volume (beta: -1.19% and -1.35% per annum per
      quartile, P<0.05 and P<0.01, respectively), independently of TNF-alpha. Change in
      IL-6 was associated with increased loss of medial and lateral tibial cartilage
      volume (beta: -1.18% and -1.06% per annum per quartile, both P<0.05) and change
      in TNF-alpha was also negatively associated with change in medial cartilage
      volume (beta: -1.27% per annum per quartile, P<0.05). CONCLUSIONS: Serum levels
      of IL-6 and TNF-alpha are associated with knee cartilage loss in older people
      suggesting low level inflammation plays a role in the pathogenesis of knee OA.

PMID- 20816982
TI  - Computational design of a chain-specific tetracycline repressor heterodimer.
AB  - The specificity and selectivity of protein-protein interactions are of central
      importance for many biological processes, including signal transduction and
      transcription control. We used the in-house side-chain packing program MUMBO to
      computationally design a chain-specific heterodimeric variant of the bacterial
      transcription regulator tetracycline repressor (TetR), called T-A(A)B. Our goal
      was to engineer two different TetR chain variants, A and B, that no longer
      interact as AA or BB homodimers but selectively recombine to form heterodimers.
      Although 56 residues from each chain contribute to a dimer interface as large as
      2200 A(2) in wild-type TetR, the substitution of only three residues in one chain
      and two residues in a second chain sufficed for generating specificity in a T
      A(A)B heterodimer variant. The design was corroborated in vivo by a cell-based
      transcription assay, and in vitro by CD spectroscopy and X-ray crystallography.
      Crystal structure analyses showed that while selectivity in the B chain is
      achieved entirely through van der Waals repulsion, the best selectivity in the A
      chain is obtained for the variant with the lowest number of atoms in the
      interface, thus possibly leading to underpacking of the dimer interface. This
      results in a marked decrease in thermal stability and a drastic reduction in the
      solubility of the T-A(A)A(A) homodimer in comparison to the designed T-A(A)B
      heterodimer variant.

PMID- 20816983
TI  - TolA modulates the oligomeric status of YbgF in the bacterial periplasm.
AB  - The trans-envelope Tol complex of Gram-negative bacteria is recruited to the
      septation apparatus during cell division where it is involved in stabilizing the
      outer membrane. The last gene in the tol operon, ybgF, is highly conserved, yet
      does not seem to be required for Tol function. We have addressed this anomaly by
      characterizing YbgF from Escherichia coli and its interaction with TolA, which,
      based on previous yeast two-hybrid data, is the only known physical link between
      YbgF and the Tol system. We show that the stable YbgF trimer undergoes a marked
      change in oligomeric state on binding TolA, forming a one-to-one complex with the
      Tol protein. Through a combination of pull-down assays, deletion analysis, and
      isothermal titration calorimetry, we map the TolA-YbgF interface to the C
      terminal tetratricopeptide repeat domain of YbgF and 31 residues at the C
      terminal end of TolA domain II (TolA(280-313)). We show that TolB, which binds
      TolA domain III close to the YbgF binding site, has no impact on the YbgF-TolA
      association. We also report the crystal structures of the two component domains
      of YbgF, the N-terminal coiled coil from E. coli YbgF, which forms a stable
      trimer and controls the oligomeric status of YbgF, and the monomeric
      tetratricopeptide repeat domain from Xanthomonas campestris YbgF, which is also
      able to trimerize. Although the coiled coil is not directly involved in TolA
      binding, we demonstrate that the regular hydrophilic patterning of its otherwise
      hydrophobic core is a prerequisite for the TolA-induced oligomeric-state
      transition of YbgF. We postulate that rather than YbgF affecting Tol function, it
      is the change in YbgF oligomeric status (with an accompanying change in its
      function) that likely explains the necessity for tight co-regulation of the ybgF
      and tol genes in Gram-negative bacteria.

PMID- 20816984
TI  - A structural hinge in eukaryotic MutY homologues mediates catalytic activity and
      Rad9-Rad1-Hus1 checkpoint complex interactions.
AB  - The DNA glycosylase MutY homologue (MYH or MUTYH) removes adenines
      misincorporated opposite 8-oxoguanine as part of the base excision repair
      pathway. Importantly, defects in human MYH (hMYH) activity cause the inherited
      colorectal cancer syndrome MYH-associated polyposis. A key feature of MYH
      activity is its coordination with cell cycle checkpoint via interaction with the
      Rad9-Rad1-Hus1 (9-1-1) complex. The 9-1-1 complex facilitates cell cycle
      checkpoint activity and coordinates this activity with ongoing DNA repair. The
      interdomain connector (IDC, residues 295-350) between the catalytic domain and
      the 8-oxoguanine recognition domain of hMYH is a critical element that maintains
      interactions with the 9-1-1 complex. We report the first crystal structure of a
      eukaryotic MutY protein, a fragment of hMYH (residues 65-350) that consists of
      the catalytic domain and the IDC. Our structure reveals that the IDC adopts a
      stabilized conformation projecting away from the catalytic domain to form a
      docking scaffold for 9-1-1. We further examined the role of the IDC using
      Schizosaccharomyces pombe MYH as model system. In vitro studies of S. pombe MYH
      identified residues I261 and E262 of the IDC (equivalent to V315 and E316 of the
      hMYH IDC) as critical for maintaining the MYH/9-1-1 interaction. We determined
      that the eukaryotic IDC is also required for DNA damage selection and robust
      enzymatic activity. Our studies also provide the first evidence that disruption
      of the MYH/9-1-1 interaction diminishes the repair of oxidative DNA damage in
      vivo. Thus, preserving the MYH/9-1-1 interaction contributes significantly to
      minimizing the mutagenic potential of oxidative DNA damage.

PMID- 20816986
TI  - Preformed protein-binding motifs in 7SK snRNA: structural and thermodynamic
      comparisons with retroviral TAR.
AB  - The 7SK small nuclear RNA is a highly conserved non-coding RNA that regulates
      transcriptional elongation. 7SK utilizes the HEXIM proteins to sequester the
      transcription factor P-TEFb by a mechanism similar to that used by retroviral TAR
      RNA to engage Tat and P-TEFb. Tat has also recently been shown to bind 7SK
      directly and recruit P-TEFb to TAR. We report here the solution structures of the
      free and arginine-bound forms of stem loop 4 of 7SK (7SK-SL4). Comparison of the
      7SK-SL4 and TAR structures demonstrates the presence of a common arginine
      sandwich motif. However, arginine binding to 7SK-SL4 is mechanistically distinct
      and occurs via docking into a pre-organized pocket resulting in a 1000-fold
      increased affinity. Furthermore, whereas formation of the binding pocket in TAR
      requires a critical base-triple, hydrogen-bond formation between the equivalent
      bases in 7SK-SL4 is not essential and the pocket is stabilized solely by a pseudo
      base-triple platform. In addition, this theme of preformed protein binding motifs
      also extends into the pentaloop. The configuration of the loop suggests that 7SK
      SL4 is poised to make ternary contacts with P-TEFb and HEXIM or Tat. These key
      differences between 7SK-SL4 and TAR present an opportunity to understand RNA
      structural adaptation and have implications for understanding differential
      interactions with Tat.

PMID- 20816985
TI  - Investigation of an anomalously accelerating substitution in the folding of a
      prototypical two-state protein.
AB  - The folding rates of two-state single-domain proteins are generally resistant to
      small-scale changes in amino acid sequence. For example, having surveyed here
      over 700 single-residue substitutions in 24 well-characterized two-state
      proteins, we find that the majority (55%) of these substitutions affect folding
      rates by less than a factor of 2, and that only 9% affect folding rates by more
      than a factor of 8. Among those substitutions that significantly affect folding
      rates, we find that accelerating substitutions are an order of magnitude less
      common than those that decelerate the process. One of the most extreme outliers
      in this data set, an arginine-to-phenylalanine substitution at position 48 (R48F)
      of chymotrypsin inhibitor 2 (CI2), accelerates the protein's folding rate by a
      factor of 36 relative to that of the wild-type protein and is the most
      accelerating substitution reported to date in a two-state protein. In order to
      better understand the origins of this anomalous behavior, we have characterized
      the kinetics of multiple additional substitutions at this position. We find that
      substitutions at position 48 in CI2 fall into two distinct classes. The first,
      comprising residues that ablate the charge of the wild-type arginine but retain
      the hydrophobicity of its alkane chain, accelerate folding by at least 10-fold.
      The second class, comprising all other residues, produces folding rates within a
      factor of two of the wild-type rate. A significant positive correlation between
      hydrophobicity and folding rate across all of the residues we have characterized
      at this position suggests that the hydrophobic methylene units of the wild-type
      arginine play a significant role in stabilizing the folding transition state.
      Likewise, studies of the pH dependence of the histidine substitution indicate a
      strong correlation between folding rate and charge state. Thus, mutations that
      ablate the arginine's positive charge while retaining the hydrophobic contacts of
      its methylene units tend to dramatically accelerate folding. Previous studies
      have suggested that arginine 48 plays an important functional role in CI2, which
      may explain why it is highly conserved despite the anomalously large deceleration
      it produces in the folding of this protein.

PMID- 20816987
TI  - Power law distribution defines structural disorder as a structural element
      directly linked with function.
AB  - Although intrinsically disordered proteins are prevalent and functionally
      important, it has never been asked whether structural disorder should be
      considered as a separate structural category on its own or merely as a lack of
      secondary and/or tertiary structure. We address this issue by showing that its
      length distribution in the human proteome follows a power law, with many short
      regions but also a significant incidence of very long disordered regions. This
      behavior is in sharp contrast with that of conventional secondary structural
      elements and is highly reminiscent of the distribution of tertiary structural
      units in proteins. We interpret this finding by the direct functional involvement
      of disorder, which distinguishes it from secondary structural elements and endows
      it with tertiary structural attributes.

PMID- 20816988
TI  - Distinct regions of human eIF3 are sufficient for binding to the HCV IRES and the
      40S ribosomal subunit.
AB  - Translation of the hepatitis C virus (HCV) genomic RNA initiates from an internal
      ribosome entry site (IRES) in its 5' untranslated region and requires a minimal
      subset of translation initiation factors to occur, namely eukaryotic initiation
      factor (eIF) 2 and eIF3. Low-resolution structural information has revealed how
      the HCV IRES RNA binds human eIF3 and the 40S ribosomal subunit and positions the
      start codon for initiation. However, the exact nature of the interactions between
      the HCV IRES RNA and the translational machinery remains unknown. Using limited
      proteolysis and mass spectrometry, we show that distinct regions of human eIF3
      are sufficient for binding to the HCV IRES RNA and the 40S subunit. Notably, the
      eIF3 subunit eIF3b is protected by HCV IRES RNA binding, yet is exposed in the
      complex when compared to subunits eIF3e, eIF3f, eIF3h, and eIF3l. Limited
      proteolysis reveals that eIF3 binding to the 40S ribosomal subunit occurs through
      many redundant interactions that can compensate for each other. These data
      suggest how the HCV IRES binds to specific regions of eIF3 to target the
      translational machinery to the viral genomic RNA and provide a framework for
      modeling the architecture of intact human eIF3.

PMID- 20816989
TI  - Carboxyl pK(a) values and acid denaturation of BBL.
AB  - The protein BBL undergoes structural transitions and acid denaturation between pH
      1.2 and 8.0. Using NMR spectroscopy, we measured the pK(a) values of all the
      carboxylic residues in this pH range. We employed (13)C direct-detection two
      dimensional IPAP (in-phase antiphase) CACO NMR spectroscopy to monitor the
      ionization state of different carboxylic groups and demonstrated its advantages
      over other NMR techniques in measuring pK(a) values of carboxylic residues. The
      two residues Glu161 and Asp162 had significantly lowered pK(a) values, showing
      that these residues are involved in a network of stabilizing electrostatic
      interactions, as is His166. The other carboxylates had unperturbed values. The pH
      dependence of the free energy of denaturation was described quantitatively by the
      ionizations of those three residues of perturbed pK(a), and, using thermodynamic
      cycles, we could calculate their pK(a)s in the native and denatured states as
      well as the equilibrium constants for denaturation of the different protonation
      states. We also measured (13)C(alpha) chemical shifts of individual residues as a
      function of pH. These shifts sense structural transitions rather than
      ionizations, and they titrated with pH consistent with the change in equilibrium
      constant for denaturation. Kinetic measurements of the folding of BBL E161Q
      indicated that, at pH 7, the stabilizing interactions with Glu161 are formed
      mainly in the transition state. We also found that local interactions still exist
      in the acid-denatured state of BBL, which attenuate somewhat the flexibility of
      the acid-denatured state.

PMID- 20816990
TI  - Making noise: emergent stochasticity in collective motion.
AB  - Individual-based models of self-propelled particles (SPPs) are a popular and
      promising approach to explain features of the collective motion of animal
      aggregations. Many models that capture some features of group motion have been
      suggested but a common framework has yet to emerge. Key to all of these models is
      the inclusion of "noise" or stochastic errors in the individual behaviour of the
      SPPs. Here, we present a fully stochastic SPP model in one dimension that
      demonstrates a new way of introducing noise into SPP models whilst preserving
      emergent behaviours of previous models such as coherent groups and spontaneous
      direction switching. This purely individual-to-individual, local model is related
      to previous models in the literature and can easily be extended to higher
      dimensions. Its coarse-grained behaviour qualitatively reproduces recently
      reported locust movement data. We suggest that our approach offers an alternative
      to current reasoning about model construction and has the potential to offer
      mechanistic explanations for emergent properties of animal groups in nature.

PMID- 20816991
TI  - Persistence and extinction of a stochastic single-species model under regime
      switching in a polluted environment II.
AB  - This is a continuation of our paper [Liu, M., Wang, K., 2010. Persistence and
      extinction of a stochastic single-species model under regime switching in a
      polluted environment, J. Theor. Biol. 264, 934-944]. Taking both white noise and
      colored noise into account, a stochastic single-species model under regime
      switching in a polluted environment is studied. Sufficient conditions for
      extinction, stochastic nonpersistence in the mean, stochastic weak persistence
      and stochastic permanence are established. The threshold between stochastic weak
      persistence and extinction is obtained. The results show that a different type of
      noise has a different effect on the survival results.

PMID- 20816992
TI  - Time-limited involvement of dorsal hippocampus in unimodal discriminative
      contextual conditioning.
AB  - Converging evidence examining the effects of post-training manipulations of the
      hippocampus suggests that the hippocampus may play a time-limited role in the
      maintenance of a variety of forms of memory. In particular, either lesions or
      inactivation of the dorsal hippocampus results in many cases in a time-limited
      retrograde impairment in nondiscriminative contextual conditioning paradigms.
      However, the extent to which hippocampal manipulations result in a time-limited
      retrograde amnesia for a variety of forms of learning has recently been called
      into question (reviewed in Sutherland, Sparks, & Lehmann (2010)). The present
      study examined the effect of inactivation of the dorsal hippocampus either 7, 28,
      or 42 days following training in an explicitly nonspatial, discriminative
      contextual conditioning paradigm (Otto & Poon, 2006; Parsons & Otto, 2008).
      Inactivation of the dorsal hippocampus resulted in a significant deficit in the
      expression of contextual conditioning at 7 and 28 days, but not 42 days,
      following training. Importantly, inactivation of the hippocampus did not affect
      either baseline freezing levels or conditioning to an explicit CS. Together with
      previous data exploring hippocampal contributions to discriminative unimodal
      contextual conditioning, these data suggest that the hippocampus may play a
      particularly prominent role in the temporary maintenance of memory in
      discriminative contextual paradigms.

PMID- 20816993
TI  - Dietary exposure to perfluorooctanoate or perfluorooctane sulfonate induces
      hypertrophy in centrilobular hepatocytes and alters the hepatic immune status in
      mice.
AB  - It is well established that exposure of mice to perfluorooctanoate (PFOA) or
      perfluorooctane sulfonate (PFOS) induces hepatomegaly and, concurrently,
      immunotoxicity. However, the effects of these perfluorochemicals on the histology
      and immune status of the liver have not been yet investigated and we have
      examined these issues here. Dietary treatment of male C57BL/6 mice with 0.002%
      (w/w) PFOA or 0.005% (w/w) PFOS for 10 days resulted in significant reductions in
      serum levels of cholesterol and triglycerides, a moderate increase in the serum
      activity of alkaline phosphatase (ALP) and hepatomegaly, without affecting other
      immune organs. This hepatomegaly was associated with marked hypertrophy of the
      centrilobular hepatocytes, with elevated numbers of cytoplasmic acidophilic
      granules and occasional mitosis. Furthermore, dietary exposure to PFOA or PFOS
      altered the hepatic immune status: whereas exposure to PFOA enhanced the numbers
      of total, as well as of phenotypically distinct subpopulations of intrahepatic
      immune cells (IHIC), and in particular the presumptive erythrocyte progenitor
      cells, treatment with PFOS enhanced only the numbers of hepatic cells that appear
      immunophenotypically to be erythrocyte progenitors, without affecting other types
      of IHIC. In addition, exposure to these compounds attenuated hepatic levels of
      tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and
      interleukin-4 (IL-4). Furthermore, the exposed animals exhibited a significant
      increase in hepatic levels of erythropoietin, a hormone required for
      erythropoiesis. Thus, in mice, PFOA- and PFOS-induced hepatomegaly is associated
      with significant alterations in hepatic histophysiology and immune status, as
      well as induction of hepatic erythropoiesis.

PMID- 20816994
TI  - Terbinafine stimulates the pro-inflammatory responses in human monocytic THP-1
      cells through an ERK signaling pathway.
AB  - AIMS: Oral antifungal terbinafine has been reported to cause liver injury with
      inflammatory responses in a small percentage of patients. However the underlying
      mechanism remains unknown. To examine the inflammatory reactions, we investigated
      whether terbinafine and other antifungal drugs increase the release of pro
      inflammatory cytokines using human monocytic cells. MAIN METHODS: Dose- and time
      dependent changes in the mRNA expression levels and the release of interleukin
      (IL)-8 and tumor necrosis factor (TNF)alpha from human monocytic THP-1 and HL-60
      cells with antifungal drugs were measured. Effects of terbinafine on the
      phosphorylation of extracellular signal-regulated kinase (ERK)1/2, p38 mitogen
      activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK)1/2 were
      investigated. KEY FINDINGS: The release of IL-8 and TNFalpha from THP-1 and HL-60
      cells was significantly increased by treatment with terbinafine but not by
      fluconazole, suggesting that terbinafine can stimulate monocytes and increase the
      pro-inflammatory cytokine release. Terbinafine also significantly increased the
      phosphorylation of ERK1/2 and p38 MAP kinase in THP-1 cells. Pretreatment with a
      MAP kinase/ERK kinase (MEK)1/2 inhibitor U0126 significantly suppressed the
      increase of IL-8 and TNFalpha levels by terbinafine treatment in THP-1 cells, but
      p38 MAPK inhibitor SB203580 did not. These results suggested that an ERK1/2
      pathway plays an important role in the release of IL-8 and TNFalpha in THP-1
      cells treated with terbinafine. SIGNIFICANCE: The release of inflammatory
      mediators by terbinafine might be one of the mechanisms underlying immune
      mediated liver injury. This in vitro method may be useful to predict adverse
      inflammatory reactions that lead to drug-induced liver injury.

PMID- 20816995
TI  - The increased CAR-dependent metabolism of thyroid hormones in mice with high
      cancer susceptibility.
AB  - AIM: our aim was to compare activation of the constitutive androstane receptor
      (CAR), hepatic expression of its target genes, and the serum thyroid hormone
      levels in C3H/He, C57BL/6J, and CC57BR/Mv mice following phenobarbital treatment.
      These differences, if present, could help to explain the different susceptibility
      to phenobarbital-induced liver tumor promotion among these strains of mice. MAIN
      METHODS: CAR DNA-binding activity and CAR content in nuclear protein extracts
      from mouse livers were assessed using the electrophoretic mobility shift assay
      and immunoblotting. Serum thyroid hormone concentrations were determined by
      radioimmunoassay. Real-time PCR was used to measure the hepatic expression level
      of CAR target genes. KEY FINDINGS: we found a 2.3-fold increase of CAR DNA
      binding activity in response to phenobarbital in the sensitive C3H/He mice, but
      no change in the relatively resistant C57BL/6J and CC57BR/Mv mice. Phenobarbital
      treatment caused a significant decrease in triiodothyronine and free thyroxine
      concentrations (17% and 40%, respectively) in the sensitive C3H/He mice by the
      end of 60-day treatment, while in the resistant mice, these changes were not
      observed. In the sensitive C3H/He mice only, the expression of a CAR target gene
      encoding sulfotransferase Sult2a1, the thyroid hormone inactivation enzyme,
      increased by 260-fold after phenobarbital administration. The expression of
      another CAR target gene, Mdm2, was also increased by phenobarbital treatment in
      C3H/He mice. SIGNIFICANCE: we have shown that phenobarbital activates CAR and
      increases the expression of its target genes thereby accelerating the metabolism
      of thyroid hormones only in mice susceptible to liver tumor promotion by
      phenobarbital, but not in relatively resistant animals.

PMID- 20816996
TI  - Pindolol potentiates the panicolytic effect of paroxetine in the elevated T-maze.
AB  - AIMS: the beta-adrenergic and 5-HT(1A) receptor antagonist pindolol has been used
      in combination with antidepressant drugs, to shorten the time of onset of
      clinical efficacy and/or increase the proportion of responders in depressive and
      anxiety disorders. The aim of this study was to examine the interaction between
      pindolol and the selective serotonin reuptake inhibitor (SSRI), paroxetine in
      rats submitted to the elevated T-maze (ETM). MAIN METHODS: for assessing the drug
      combination effect, rats were administered with pindolol before paroxetine, using
      oral or intraperitoneal (i.p.) routes of acute administration, and were submitted
      to the ETM model. KEY FINDINGS: the highest dose of pindolol used (15.0mg/kg,
      i.p.) increased both inhibitory avoidance and escape latencies in the ETM,
      probably due to nonspecific motor deficit, since locomotion in a circular arena
      was also significantly decreased. The highest dose of paroxetine (3.0mg/kg, i.p.)
      selectively impaired escape, considered a panicolytic effect. Combination of
      pindolol (5.0mg/kg, i.p.) with an ineffective dose of paroxetine (1.5mg/kg, i.p.)
      impaired escape, indicating a potentiation of the panicolytic effect of
      paroxetine. By the oral route, neither paroxetine (3.0mg/kg) nor pindolol
      (5.0mg/kg) alone were effective, but the combination treatment had a marked
      panicolytic effect, again indicating drug potentiation. SIGNIFICANCE: the present
      results show that the combination of the ineffective doses of pindolol and
      paroxetine significantly increased escape latency, indicating a selective
      panicolytic effect. These findings give preclinical support for the use of this
      drug combination in the treatment of panic disorder (PD).

PMID- 20816997
TI  - Bacteriophage treatment significantly reduces viable Clostridium difficile and
      prevents toxin production in an in vitro model system.
AB  - Clostridium difficile is primarily a nosocomial pathogen, causing thousands of
      cases of antibiotic-associated diarrhoea in the UK each year. In this study, we
      used a batch fermentation model of a C. difficile colonised system to evaluate
      the potential of a prophylactic and a remedial bacteriophage treatment regime to
      control the pathogen. It is shown that the prophylaxis regime was effective at
      preventing the growth of C. difficile (p = <0.001) and precluded the production
      of detectable levels of toxins A and B. The remedial treatment regime caused a
      less profound and somewhat transient decrease in the number of viable C.
      difficile cells (p = <0.0001), but still resulted in a lower level of toxin
      production relative to the control. The numbers of commensal bacteria including
      total aerobes and anaerobes, Bifidobacterium sp., Bacteroides sp., Lactobacillus
      sp., total Clostridium sp., and Enterobacteriaceae were not significantly
      decreased by this therapy, whereas significant detrimental effects were observed
      with metronidazole treatment. Our study indicates that phage therapy has
      potential to be used for the control of C. difficile; it highlights the main
      benefits of this approach, and some future challenges.

PMID- 20816998
TI  - Presence of periodontopathic bacteria in coronary arteries from patients with
      chronic periodontitis.
AB  - In this study the presence of periodontopathic pathogens in atheromatous plaques
      removed from coronary arteries of patients with chronic periodontitis and
      periodontally healthy subjects by PCR was detected. Our results indicate a
      significant association between the presence of Porphyromonas gingivalis and
      atheromas, and the periodontal bacteria in oral biofilm may find a way to reach
      arteries.

PMID- 20816999
TI  - Priors for the Bayesian star paradox.
AB  - We show that the Bayesian star paradox, first proved mathematically by Steel and
      Matsen for a specific class of prior distributions, occurs in a wider context
      including less regular, possibly discontinuous, prior distributions.

PMID- 20817000
TI  - Amino acid divergence between the CHS domain contributes to the different
      intracellular behaviour of Family II fungal chitin synthases in Saccharomyces
      cerevisiae.
AB  - Family II chitin synthases (CS), including classes IV and V enzymes, share
      conserved catalytic domains flanked by transmembrane regions. Here we addressed
      the characterization of Family II fungal CSs by heterologous expression in
      Saccharomyces cerevisiae. Full-length CSs from classes V or IV were not
      functional when expressed in S. cerevisiae and accumulated in different
      intracellular compartments. However, the exchange between different class IV, but
      not of class V, CHS domains resulted in functional proteins both in vivo and in
      vitro. The different domains afford the chimeric proteins distinct intracellular
      behaviours, ranging from endoplasmic reticulum retention to reduced endocytic
      turnover at the plasma membrane. These results allow a role in chitin synthesis
      to be assigned to all class IV enzymes, but they also highlight the involvement
      of the intracellular globular domain of these CSs, not only in enzymatic activity
      but also in the regulation of their intracellular turnover.

PMID- 20817001
TI  - Depletion of DSS1 protein disables homologous recombinational repair in human
      cells.
AB  - DSS1 is a small, highly acidic protein widely conserved among eukaryotes as a
      component of the 19S proteasome and implicated in ubiquitin-mediated proteolysis.
      The BRCA2 tumor suppressor protein functions in homologous recombinational repair
      (HRR) of DNA double-strand breaks, and does so in part through the actions of a
      carboxy-proximal region that binds DNA and several other proteins, including
      DSS1. In the unicellular eukaryote Ustilago maydis, Dss1 interacts with Brh2, a
      BRCA2-like protein, and regulates its function in mediating HRR. We used RNA
      interference to deplete DSS1 in human cells, and assayed the effects on double
      strand break repair by homologous recombination. Partial depletion of DSS1
      protein in human cells reduced the efficiency of HRR to small fractions of normal
      levels. Residual HRR activity correlated roughly with the residual level of DSS1
      expression. The results imply that mammalian DSS1 makes a critical contribution
      to the function of BRCA2 in mediating HRR, and hence to genomic stability.
      Activity of the ubiquitin-proteasome system can influence HRR. However, treatment
      with proteasome inhibitors only partially reproduced the effects of DSS1
      depletion on HRR, suggesting that the function of DSS1 in HRR involves more than
      proteolysis per se.

PMID- 20817002
TI  - Isolation, biochemical characterization, and molecular modeling of American
      lobster digestive cathepsin D1.
AB  - An aspartic proteinase was isolated from American lobster gastric fluid. The
      purified cathepsin D runs as a single band on native-PAGE displaying proteolytic
      activity on a zymogram at pH 3.0, with an isoelectric point of 4.7. Appearance of
      the protein in SDS-PAGE, depended on the conditions of the gel electrophoresis.
      SDS treatment by itself was not able to fully unfold the protein. Thus, in SDS
      PAGE the protein appeared to be heterogeneous. A few minute of boiling the sample
      in the presence of SDS was necessary to fully denature the protein that then run
      in the gel as a single band of ~50 kDa. The protein sequence of lobster cathepsin
      D1, as deduced from its mRNA sequence, lacks a 'polyproline loop' and beta
      hairpin, which are characteristic of some of its structural homologues. A
      comparison of amino acid sequences of digestive and non-digestive cathepsin D
      like enzymes from invertebrates showed that most cathepsin D enzymes involved in
      food digestion, lack the polyproline loop, whereas all non-digestive cathepsin
      Ds, including the American lobster cathepsin D2 paralog, contain the polyproline
      loop. We propose that the absence or presence of this loop may be characteristic
      of digestive and non-digestive aspartic proteinases, respectively.

PMID- 20817003
TI  - Individual differences in nonverbal number discrimination correlate with event
      related potentials and measures of probabilistic reasoning.
AB  - The current study investigated the neural activity patterns associated with
      numerical sensitivity in adults. Event-related potentials (ERPs) were recorded
      while adults observed sequentially presented display arrays (S1 and S2) of non
      symbolic numerical stimuli (dots) and made same/different judgments of these
      stimuli by pressing a button only when numerosities were the same (target
      trials). The main goals were to contrast the effects of numerical distance
      (close, medium, and far) and change direction (increasing, decreasing) between S1
      and S2, both in terms of behavior and brain activity, and to examine the
      influence of individual differences in numeracy on the effects of these
      manipulations. Neural effects of distance were found to be significant between
      360 and 600 ms after the onset of S2 (greater negativity-wave activity for closer
      numerical distances), while direction effects were found between 320 and 440 ms
      (greater negativity for decreasing direction). ERP change direction effects did
      not interact with numerical distance, suggesting that the two types of
      information are processed independently. Importantly, subjects' behavioral Weber
      fractions (w) for the same/different discrimination task correlated with distance
      related ERP-activity amplitudes. Moreover, w also correlated with a separate
      objective measure of mathematical ability. Results thus draw a clear link between
      brain and behavior measures of number discrimination, while also providing
      support for the relationship between nonverbal magnitude discrimination and
      symbolic numerical processing.

PMID- 20817004
TI  - Anion exchanger 1: Protean function and associations.
AB  - Anion exchanger 1 (AE1) is the most abundant protein on the erythrocyte membrane
      and is also present on the basolateral surface of the alpha intercalated cell in
      the distal nephron. Mutations can cause either hereditary haemolytic red cell
      diseases, or hereditary distal renal tubular acidosis. Classically it mediates
      the electroneutral exchange of chloride for bicarbonate, as well as comprising an
      important mechanical component of the red cell membrane. It is increasingly
      recognised that it plays many other roles too: alternative anion transport, such
      as sulphate transport and proton and sulphate symport, associations with other
      erythrocyte membrane proteins as part of the AE1 macrocomplex, regulation of
      glycolysis and more recently cation transport through the so-called 'leak'
      pathway. These new functions and associations are reviewed in health and disease,
      and the role of AE1 as a putative regulator of cell volume is discussed.

PMID- 20817005
TI  - BACE: Therapeutic target and potential biomarker for Alzheimer's disease.
AB  - beta-Site APP-cleaving enzyme (BACE) is a membrane-bound aspartyl protease
      involved in the production of Alzheimer's disease (AD) Abeta amyloid peptides.
      This enzyme is ubiquitously expressed, with highest levels in the brain and
      pancreas. Its cellular trafficking is tightly controlled as it recycles between
      endosomes and trans-Golgi network. BACE expression increases in response to aging
      and various stress stimuli. It is elevated in the brain cortex of AD sufferers,
      and increased levels of BACE in the cerebrospinal fluid of patients with mild
      cognitive impairment may provide an early biomarker of AD. BACE is considered as
      a rational drug target for AD therapy, and inhibitors are under development.
      Anomalies in the behaviour and biochemistry of BACE(-/-) mice have pointed to the
      role this enzyme plays in the processing of neuregulin and of voltage-gated
      sodium channel beta-subunit. A full understanding of BACE biology in health and
      disease is needed to establish a safe AD therapy based on BACE inhibitors.

PMID- 20817006
TI  - Iminosugars past, present and future: medicines for tomorrow.
AB  - Iminosugars comprise the most attractive class of carbohydrate mimetics reported
      to date and are ideally positioned to take advantage of our increasing
      understanding of glycobiology in the search for new medicines. First-generation
      iminosugar drugs suffered from lack of adequate selectivity, resulting in
      considerable side-effects in the clinic. Current efforts directed towards second
      generation compounds, encompassing a much greater range of structures and
      addressing a wider selection of biochemical targets, are enabling the
      identification and development of suitable candidates that benefit from improved
      activity and selectivity. Furthermore, second-generation compounds can address a
      variety of established targets that have previously proved refractory to other
      compound classes. This review focuses on the breadth of opportunities provided by
      second-generation leads from iminosugars (SeglinsTM).

PMID- 20817007
TI  - Chromosomal instability and telomere lengths of each chromosomal arm measured by
      Q-FISH in human fibroblast strains prior to replicative senescence.
AB  - We monitored the telomere lengths and chromosomal instability characteristics of
      fibroblasts at different population doubling levels (PDLs) to gain further
      insight into the role of telomere shortening in chromosomal instability. We used
      7 normal diploid human fibroblast strains (TIG-1, 3, 7, 103, 104, 112, and 114)
      and a quantitative fluorescence in situ hybridization method to measure telomere
      lengths of the p- and q-arms of individual chromosomes. We also enumerated
      morphologic signs of chromosomal instability, including fusion or loss of
      chromosomes, and anaphase bridges. In strains TIG-1, 3, 7, 103, and 114 at the
      late (phase 3) stage (?40PDLs), 29 (96.6%) of 30 fusions were associated with one
      or both of the chromosomal arms that bear significantly shorter telomeres in
      those populations. In TIG-1 at 62PDL, 6 fusions were associated with Xq (n=3),
      21q (n=3), and other (n=6) chromosomes. Xq and 21q had significantly shorter
      telomeres, and anaphase bridges were often associated with chromosomes X and/or
      21 (74.6%). Our results indicate that chromosomes having excessively shortened
      telomeres at late PDLs begin to show features of instability such as fusions and
      anaphase bridges.

PMID- 20817008
TI  - Interplay of cysteinyl leukotrienes and TGF-beta in the activation of hepatic
      stellate cells from Schistosoma mansoni granulomas.
AB  - Hepatic stellate cells (HSCs) have a critical role in liver physiology, and in
      the pathogenesis of liver inflammation and fibrosis. Here, we investigated the
      interplay between leukotrienes (LT) and TGF-beta in the activation mechanisms of
      HSCs from schistosomal granulomas (GR-HSCs). First, we demonstrated that GR-HSCs
      express 5-lipoxygenase (5-LO), as detected by immunolocalization in whole cells
      and confirmed in cell lysates through western blotting and by mRNA expression
      through RT-PCR. Moreover, mRNA expression of 5-LO activating protein (FLAP) and
      LTC(4)-synthase was also documented, indicating that GR-HSCs have the molecular
      machinery required for LT synthesis. Morphological analysis of osmium and Oil-Red
      O-stained HSC revealed large numbers of small lipid droplets (also known as lipid
      bodies). We observed co-localization of lipid droplet protein marker (ADRP) and 5
      LO by immunofluorescence microscopy. We demonstrated that GR-HSCs were able to
      spontaneously release cysteinyl-LTs (CysLTs), but not LTB(4,) into culture
      supernatants. CysLT production was highly enhanced after TGF-beta-stimulation.
      Moreover, the 5-LO inhibitor zileuton and 5-LO gene deletion were able to inhibit
      the TGF-beta-stimulated proliferation of GR-HSCs, suggesting a role for LTs in
      HSC activation. Here, we extend the immunoregulatory function of HSC by
      demonstrating that HSC from liver granulomas of schistosome-infected mouse are
      able to release Cys-LTs in a TGF-beta-regulated manner, potentially impacting
      pathogenesis and liver fibrosis in schistosomiasis.

PMID- 20817009
TI  - Absence of repeated-trial tolerance to the anxiolytic-like effects of
      chlordiazepoxide in the rat triple test.
AB  - The triple test, recently developed to assess anxiety-related behaviors in
      rodents, combines three widely used behavioral tests: the open field (OF),
      elevated plus maze (EPM) and light/dark box (LDB). The EPM and LDB, individually,
      are normally sensitive to the anxiolytic effects of benzodiazepines only in the
      first trial, due to the phenomenon of one-trial tolerance, which limits their use
      in longitudinal studies. The main objective of the present investigation was to
      verify whether the anxiolytic-like effects of chlordiazepoxide (CDZ), previously
      observed in naive animals submitted to the triple test, would persist after
      repeated testing. To this end, three experiments were carried out where male
      Wistar rats received CDZ (10mg/kg) 30min before the triple test for 2, 3 or 20
      consecutive days. Except for the first day of drug treatment following a previous
      test experience in an undrugged state, CDZ had enduring anxiolytic-like effects
      under all schedules, promoting an increase in the exploration of the EPM open
      arms (and in some cases of the white compartment of the LDB), without affecting
      the number of closed-arm entries. The finding that rats did not develop tolerance
      to CDZ even with chronic treatment and repeated exposures to the triple test
      suggests that this new device is a promising tool to be used in longitudinal
      studies involving pharmacological manipulations of anxiety-related behaviors.

PMID- 20817010
TI  - DNA vaccine with alpha-galactosylceramide at prime phase enhances anti-tumor
      immunity after boosting with antigen-expressing dendritic cells.
AB  - DNA vaccines contribute to a promising new approach for the generation of
      cytotoxic T lymphocytes (CTL). DNA vaccines do have several disadvantages,
      including poor immunogenicity and oncogene expression. We used the natural killer
      T-cell (NKT) ligand alpha-galactosylceramide (alpha-GalCer) as an adjuvant to
      prime initial DNA vaccination; and used the potent immune-stimulatory tumor
      antigen-expressing dendritic cells (DCs) as a booster vaccination. A DNA vaccine
      expressing human papillomavirus (HPV) type 16 E7 (pcDNA3-CRT/E7) was combined
      with alpha-GalCer at the prime phase, and generated a higher number of E7
      specific CD8(+) T-cells in vaccinated mice than vaccine used at boost phase.
      Therefore, priming with a DNA vaccine in the presence of alpha-GalCer and
      boosting with E7-pulsed DC-1 led to a significant enhancement of E7-specific
      CD8(+) effector and memory T-cells as well as significantly improved therapeutic
      and preventive effects against an E7-expressing tumor model (TC-1) in vaccinated
      mice. Our findings suggested that the potency of a DNA vaccine combined with
      alpha-GalCer could be further enhanced by boosting with an antigen-expressing DC
      based vaccine to generate anti-tumor immunity.

PMID- 20817011
TI  - Acceptance of the 2009 A(H1N1) influenza vaccine among hospital workers in two
      French cancer centers.
AB  - The aim of the study was to determine predictive factors influencing the
      acceptance of the 2009 A(H1N1) influenza vaccination among hospital workers (HW)
      in two French cancer centers. A standardized, anonymous, self-administered
      questionnaire was sent to HW of two cancer centers. The survey response rate was
      26.2% (n=506). Main reasons for A(H1N1) vaccination acceptance were "to protect
      my relatives" (30.3%), "to protect myself" (30.3%). Main reasons for A(H1N1)
      vaccination refusal were the fear of side effects (43.1%), doubt about the
      vaccine's efficacy (25.8%). Vaccinated HW were more influenced by the
      institutional campaign (p<0.001) or colleagues' advice (p<0.001) whereas non
      vaccinated HW were influenced by their family physician's advice (p=0.03),
      personal conviction (p<0.001) or the media (p<0.001). A multivariate analysis
      revealed age (>35 vs <= 35), prior seasonal influenza vaccination, professional
      category and source of information to be predictive factors of vaccination.
      Future vaccination campaigns will need to focus on young HW (<= 35-year old),
      with no prior influenza vaccination and HW who are in contact with patients and
      who reported low seasonal influenza vaccination rates.

PMID- 20817012
TI  - Tumor therapy in mice by using a tumor antigen linked to modulin peptides from
      Staphylococcus epidermidis.
AB  - Staphylococcus epidermidis releases a complex of at least four peptides, termed
      phenol-soluble modulins (PSM), which stimulate macrophages to produce
      proinflammatory cytokines via activation of TLR2 signalling pathway. We
      demonstrated that covalent linkage of PSM peptides to an antigen facilitate its
      capture by dendritic cells and, in combination with different TLR ligands, can
      favour the in vivo induction of strong and persistent antigen-specific immune
      responses. Treatment of mice grafted with HPV16-E7-expressing tumor cells (TC-1)
      with poly(I:C) and a peptide containing alphaMod linked to the H-2D(b)-restricted
      cytotoxic T-cell epitope E7(49-57) from HPV16-E7 protein allowed complete tumor
      regression in 100% of the animals. Surprisingly, this immunomodulatory property
      of modulin-derived peptides was TLR2 independent and partially dependent upon the
      EGF-receptor signalling pathway. Our results suggest that alpha or gamma modulin
      peptides may serve as a suitable antigen carrier for the development of anti
      tumoral or anti-viral vaccines.

PMID- 20817013
TI  - A clinical study to assess the immunogenicity and safety of a monovalent 2009
      influenza A (H1N1) vaccine in an area with low-level epidemics of pandemic
      influenza.
AB  - We conducted a multi-center, randomized, laboratory-blinded clinical trial in 185
      healthy adults (<60 years) and 107 elders (>60 years) to examine the
      immunogenicity and safety of different doses of an inactivated, monovalent, non
      adjuvanted, split vaccine against the 2009 pandemic influenza A (H1N1) virus. The
      186 adults were assigned to three treatment groups, i.e., one 15 MUg
      hemagglutination (HA) antigen dose, two 15 MUg or 30 MUg HA doses in 3 weeks
      apart, and the 107 elders were treated with two 15 MUg or 30 MUg doses in 3 weeks
      apart. Prior to the vaccination, 4.8% subjects had hemagglutination-inhibition
      (HAI) antibody titers of 1:40 or more. By day 21 post-vaccination of one dose of
      15 MUg HA, the seroprotective rate was 95.1% and 75.5% in subjects <60 and >65
      years of age, respectively; by day 21 post the second 15 MUg HA dose, the
      seroprotective rates were 93.2% and 73.1%, respectively. The seroprotective rates
      for recipients of 30 MUg HA antigen by day 21 were 95.2% for subjects <60 years
      and 81.1% for subjects >65 years of age, that was boosted to 98.3% and 80.4%,
      respectively with a second dose of 30 MUg HA antigen. No vaccine-related serious
      adverse events occurred. The data indicated a single 15 MUg HA dose of the
      vaccine induced a protective immune response in most adults, including the elders
      >60 years of age, and a booster dose at the third week did not render a higher
      level of antibody response.

PMID- 20817014
TI  - Physicians' opinions about critical attributes of a potential group A
      streptococcal vaccine.
AB  - A group A streptococcal (GAS) vaccine, while not currently available, offers the
      possibility of a more effective approach; however, barriers to its implementation
      are likely to exist. The objectives of this study were to describe the attitudes
      of physicians about the importance of preventing GAS-associated conditions and to
      identify potential barriers to vaccine implementation. Surveys were sent to
      randomly selected physicians from the AAP and the AAFP. The GAS conditions
      believed by respondents to be most important to prevent among pediatric patients
      were ARF (31%) followed by STSS (24%) and pharyngitis (20%). Pediatricians and
      family physicians identified similar factors that would encourage routine use of
      a GAS vaccine. Less than half of pediatricians and only a third of family
      physicians would recommend a GAS vaccine if it could not be given concurrently
      with other immunizations or if there were strong parental resistance to the
      vaccine. This descriptive study provides important information about the
      anticipated use of a GAS vaccine by primary care physicians in the United States.

PMID- 20817015
TI  - Elusive atrial substrate: complex fractionated atrial electrograms and beyond.
AB  - Most practitioners of atrial fibrillation (AF) ablation have attempted to move
      beyond pulmonary vein isolation into the realm of physiology-driven ablation for
      patients with persistent AF. This new strategy involves a combination of a common
      anatomic approach (with isolation of the pulmonary veins) and an individualized
      strategy tailored to the electrophysiologic characteristics of the atrial
      substrate present in each patient. In this review, we summarize the current
      reasoning and controversies related to this new approach. In addition, we attempt
      to unravel some of the complexities of targeting these patient-specific atrial
      electrical signals.

PMID- 20817016
TI  - Differential heart rate dynamics in transient left ventricular apical and
      midventricular ballooning.
AB  - BACKGROUND: The aim of the present study was to assess potential differences in
      cardiac autonomic nervous modulation in patients with transient left ventricular
      apical ballooning syndrome (AB) and the midventricular variant (MB) of this
      syndrome. OBJECTIVE: We hypothesized that differences in regional distribution of
      cardiac autonomic innervation in AB and MB may induce alterations in autonomic
      modulation, and we tested this assumption by using a combination of traditional
      and novel nonlinear parameters of heart rate variability (HRV). METHODS: In a
      prospective single-center study, 49 consecutive patients with transient left
      ventricular dysfunction syndrome underwent Holter electrocardiographic recording
      on the third day after admission. A total of 27 recordings of patients with AB
      and 10 recordings of patients with MB were valid for analysis of HRV, nonlinear
      dynamic measures of HRV, detrended fluctuation analysis (DFA), and phase
      rectified signal averaging (PRSA). RESULTS: There were no significant differences
      in baseline clinical characteristics between AB and MB patients. Patients with MB
      showed significantly lower values for mean RR interval (835 +/- 104 ms vs. 908 +/
      118 ms; P < .05), 1/f power law slope (-1.28 +/- 0.2 vs. -1.13 +/- 0.2; P <
      .01), and deceleration capacity (DC) (4.6 +/- 1.4 ms vs. 6.0 +/- 1.4 ms; P <
      .01), and significantly higher values for low-frequency (LF) spectral component
      (5.3 +/- 0.5 ln ms(2)/Hz vs. 4.8 +/- 0.5 ln ms(2)/Hz), LF/high-frequency (HF)
      (1.7 +/- 0.9 ms vs. 1.3 +/- 0.6 ms; P < .05), and DFA alpha1 (1.09 +/- 0.1 vs.
      0.99 +/- 0.1; P < .01) than patients with AB. There were no significant
      correlations between parameters of HRV, DFA, 1/f power law slope, and PRSA.
      CONCLUSION: There are significant differences in heart rate dynamics between AB
      and MB syndromes. Patients with MB show stronger fractal correlations of heart
      rate dynamics. Thus, inhomogeneous efferent bilateral sympathetic coactivation
      and differences in reflex autonomic regulation may be underlying
      pathophysiological mechanisms for AB and MB syndromes.

PMID- 20817018
TI  - Linear ablation of atrial fibrillation: what does it do?

PMID- 20817017
TI  - Mutations in the cardiac L-type calcium channel associated with inherited J-wave
      syndromes and sudden cardiac death.
AB  - BACKGROUND: L-type calcium channel (LTCC) mutations have been associated with
      Brugada syndrome (BrS), short QT (SQT) syndrome, and Timothy syndrome (LQT8).
      Little is known about the extent to which LTCC mutations contribute to the J-wave
      syndromes associated with sudden cardiac death. OBJECTIVE: The purpose of this
      study was to identify mutations in the alpha1, beta2, and alpha2delta subunits of
      LTCC (Ca(v)1.2) among 205 probands diagnosed with BrS, idiopathic ventricular
      fibrillation (IVF), and early repolarization syndrome (ERS). CACNA1C, CACNB2b,
      and CACNA2D1 genes of 162 probands with BrS and BrS+SQT, 19 with IVF, and 24 with
      ERS were screened by direct sequencing. METHODS/RESULTS: Overall, 23 distinct
      mutations were identified. A total of 12.3%, 5.2%, and 16% of BrS/BrS+SQT, IVF,
      and ERS probands displayed mutations in alpha1, beta2, and alpha2delta subunits
      of LTCC, respectively. When rare polymorphisms were included, the yield increased
      to 17.9%, 21%, and 29.1% for BrS/BrS+SQT, IVF, and ERS probands, respectively.
      Functional expression of two CACNA1C mutations associated with BrS and BrS+SQT
      led to loss of function in calcium channel current. BrS probands displaying a
      normal QTc had additional variations known to prolong the QT interval.
      CONCLUSION: The study results indicate that mutations in the LTCCs are detected
      in a high percentage of probands with J-wave syndromes associated with inherited
      cardiac arrhythmias, suggesting that genetic screening of Ca(v) genes may be a
      valuable diagnostic tool in identifying individuals at risk. These results are
      the first to identify CACNA2D1 as a novel BrS susceptibility gene and CACNA1C,
      CACNB2, and CACNA2D1 as possible novel ERS susceptibility genes.

PMID- 20817019
TI  - Cryoballoon versus radiofrequency catheter ablation of paroxysmal atrial
      fibrillation: biomarkers of myocardial injury, recurrence rates, and pulmonary
      vein reconnection patterns.
AB  - BACKGROUND: Cryoballoon ablation has emerged as a novel treatment strategy for
      patients with atrial fibrillation (AF). OBJECTIVE: The purpose of this study was
      to compare pulmonary vein isolation (PVI) using cryoballoon ablation versus RF
      ablation with regard to myocardial injury, pulmonary vein (PV) reconnection
      patterns, and outcome. METHODS: Fifty patients (age 59 +/- 9 years, ejection
      fraction 0.59 +/- 0.06, left atrial size 41 +/- 5 mm) with paroxysmal AF were
      studied. Twenty-five patients underwent PVI using a 28-mm cryoballoon. A control
      group of 25 patients underwent PVI using an open-irrigation RF ablation catheter.
      Myocardial injury was determined by measuring troponin T (TnT). PV reconnection
      patterns were studied in case of repeat procedures. RESULTS: Procedure duration
      was 166 +/- 32 minutes in the cryoballoon group versus 197 +/- 52 minutes in the
      RF group (P = .014), with similar ablation times (cryoballoon: 45 minutes
      [interquartile range 40-52.5 minutes]; RF: 47 minutes [interquartile range 44-65
      minutes], P = .17). Postprocedural TnT in the RF group was 1.29 +/- 0.41 MUg/L
      versus 0.76 +/- 0.55 MUg/L in the cryoballoon group (P = .002). In 12 patients
      who underwent repeat ablation, 74% of PV reconnection sites were inferiorly
      located in the cryoballoon group compared to 17% in the RF group (P = .0004).
      With 1.2 +/- 0.4 and 1.3 +/- 0.6 procedures per patient, 88% of patients in the
      cryoballoon group and 92% in the RF group were in stable sinus rhythm after
      follow-up of 12 +/- 3 months (P = NS). CONCLUSION: Differences in the extent of
      myocardial injury and patterns of PV reconnection were observed between
      cryoballoon ablation and RF ablation of paroxysmal AF.

PMID- 20817020
TI  - Tobacco smoking in an Australian university sample and implications for health
      promotion.

PMID- 20817021
TI  - Cardiovascular risk according to educational status in India.
AB  - OBJECTIVE: Influence of socioeconomic status on cardiovascular risk has not been
      well studied in low income countries. To determine risks in various educational
      status (ES) subjects we performed a study in India. METHODS: Epidemiological
      study was performed in years 1999-2003 in Jaipur (India) for coronary risk
      factors among 1280 adults 20-59 years (men 619, women 661). ES was categorized
      into low (education <=5 years); middle (6-12 years) and high (>12 years).
      Prevalence of risk factors and Framingham risk scores were determined. RESULTS:
      Low ES was in 306, middle in 436 and high in 538. In low, middle and high ES
      respectively age-adjusted prevalence (%) of smoking was 19.0, 19.3, and 11.7;
      obesity 9.5, 16.7, and 22.1, hypertension 15.3, 30.5, and 44.0;
      hypercholesterolemia >=200mg/dl 46.0, 48.4, and 54.6; low HDL cholesterol
      <40mg/dl 46.4, 56.4, and 38.3; metabolic syndrome 20.9, 25.7, and 28.6; and
      diabetes 6.9, 5.5, and 26.4. Framingham risk score was 5.7+/-4.8, 6.3+/-5.7 and
      4.7+/-5.1 and calculated cardiovascular risk probability 5.2+/-5.7, 6.8+/-7.8 and
      5.2+/-6.0 (P(trend)<0.05). Framingham risk score was significantly greater in low
      and middle ES (6.1+/-5.3) compared to high (4.7+/-5.1) (p<0.001). Adjustment for
      smoking attenuated the risk. CONCLUSION: Low and middle educational status urban
      subjects in India have greater cardiovascular risk.

PMID- 20817022
TI  - Dyslipidemia in Shanghai, China.
AB  - OBJECTIVES: To determine the prevalence of and risk factors for dyslipidemia in
      Shanghai. METHODS: A cross-sectional survey of 14,385 subjects (6150 men) with
      mean age of 49.5 (14.5) years was conducted between October 2002 and April 2003
      using randomized, stratified cluster sampling. Serum triglyceride, total
      cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) were measured.
      RESULTS: Dyslipidemia, as defined by NCEP ATP III criteria, occurred in 5255
      subjects (36.5%). The prevalences of mixed hyperlipidemia (elevated TC and
      triglycerides), isolated hypertriglyceridemia, isolated hypercholesterolemia and
      isolated low HDL-C were 3.8%, 24.9%, 3.2% and 4.7%, respectively. The prevalence
      of dyslipidemia increased with age, with the peak prevalence (43%) occurring
      after age 55. Dyslipidemia was more common in males than females (40.2% vs.
      33.8%) and in rural than urban populations (44.2% vs. 32.3%). Serum triglyceride
      and TC increased with body mass index (BMI) and waist circumference. Mean serum
      triglyceride concentrations in males and rural residents were higher than those
      in females and urban residents, respectively, whereas the reverse was true for
      HDL-C values. Multivariate analysis revealed that dyslipidemia was associated
      with age, gender, area of residence, BMI and waist circumference. CONCLUSIONS:
      There is a high prevalence of dyslipidemia, mainly hypertriglyceridemia and low
      HDL-C, in Shanghai.

PMID- 20817023
TI  - Emerging tobacco products: hookah use among New Jersey youth.
AB  - OBJECTIVE: A national surveillance system to track hookah use by adolescents does
      not exist. A growing body of evidence suggests that high school-aged students are
      experimenting with this form of tobacco. This study adds to the current
      literature by providing prevalence estimates and factors associated with hookah
      use among New Jersey high school students. METHOD: This study explores factors
      associated with hookah use using 2008 NJYTS data. The 2008 NJYTS was a self
      reported, paper-and-pencil, cross-sectional survey of a representative sample of
      3010 high school students. RESULTS: 9.7% of NJ high school students are current
      hookah users. Predictors of hookah use included those who identified as Asian,
      concurrent tobacco users, perceiving that cigars are safer than cigarettes, or
      perceiving that smoking looks cool. CONCLUSION: The prevalence of hookah use,
      higher likelihood of concurrent tobacco use among hookah users, and
      misperceptions of safety and popularity of hookah among NJ adolescents are cause
      for concern and action. The development and regular implementation of
      standardized hookah prevalence questions into our national and state surveillance
      systems, as well as targeted, state-specific youth education and prevention
      activities are essential to thwart this growing public health concern.

PMID- 20817024
TI  - Recent insights into a new hydrodynamics of the cerebrospinal fluid.
AB  - According to the traditional hypothesis, the cerebrospinal fluid (CSF) is
      secreted inside the brain ventricles and flows unidirectionally along
      subarachnoid spaces to be absorbed into venous sinuses across arachnoid villi
      and/or via paraneural sheaths of nerves into lymphatics. However, according to
      recent investigations, it appears that interstitial fluid (ISF) and CSF are
      formed by water filtration across the walls of arterial capillaries in the
      central nervous system (CNS), while plasma osmolytes are sieved (retained) so
      that capillary osmotic counterpressure is generated, which is instrumental in
      ISF/CSF water absorption into venous capillaries and postcapillary venules. This
      hypothesis is supported by experiments showing that water, which constitutes 99%
      of CSF and ISF bulk, does not flow along CSF spaces since it is rapidly absorbed
      into adjacent CNS microvessels, while distribution of other substances along CSF
      spaces depends on the rate of their removal into microvessels: faster removal
      means more limited distribution. Furthermore, the acute occlusion of aqueduct of
      Sylvius does not change CSF pressure in isolated ventricles, suggesting that the
      formation and the absorption of CSF are in balance. Multidirectional distribution
      of substances inside CSF, as well as between CSF and ISF, is caused by to-and-fro
      pulsations of these fluids and their mixing. Absorption of CSF into venous
      sinuses and/or lymphatics under the physiological pressure should be of minor
      importance due to their minute surface area in comparison to the huge absorptive
      surface area of microvessels.

PMID- 20817025
TI  - Expression of candidate markers for stem/progenitor cells in the inner ears of
      developing and adult GFAP and nestin promoter-GFP transgenic mice.
AB  - Loss of hair cells in the mammalian cochlea leads to permanent sensori-neural
      hearing loss. Hair cells degenerate and their places are taken by phalangeal
      scars formed by non-sensory supporting cells. Current data indicate that early
      postnatal post-mitotic supporting cells can proliferate and differentiate into
      hair cell-like cells in culture. In this study, we used GFAP and nestin promoter
      GFP transgenic mice in combination with other stem cell markers to characterize
      supporting cell subtypes in the postnatal day-3 (P3) and adult organs of Corti
      with potential stem/progenitor cell phenotype. In P3 organ of Corti, we show GFAP
      GFP signal in all the supporting cell subtypes while the nestin-GFP was
      restricted to the supporting cells in the inner hair cell area. At this stage,
      GFAP and selected stem/progenitor markers displayed overlapping expression
      pattern in the supporting cell population. In the adult, GFAP expression is down
      regulated from the supporting cells in the outer hair cell area and nestin
      expression is down-regulated in the supporting cells of the inner hair cell area.
      Sox2 and Jagged1 expression is maintained in the mature supporting cells, while
      Abcg2 was down-regulated in these cells. In contrast, GFAP and Abcg2 expression
      was up-regulated in the inner sulcus limbal cells outside the mature organ of
      Corti's area. Using quantitative reverse transcription-PCR, we found a decrease
      in transcripts for Jagged1 and Sox2 in adult cochleae. Our findings suggest that
      the loss of regenerative capacity of the adult organ of Corti is related to down
      regulation of stem/progenitor key-markers from the mature supporting cells.

PMID- 20817026
TI  - Developmental expression of sorting nexin 3 in the mouse central nervous system.
AB  - We previously reported that sorting nexin 3 (SNX3), a protein belonging to the
      sorting nexin family, regulates neurite outgrowth in mouse N1E-115 neuroblastoma
      cells. The snx3 gene is disrupted in patients with microcephaly, microphthalmia,
      ectrodactyly, and prognathism (MMEP) and mental retardation, demonstrating that
      SNX3 plays an important role in the genesis of these organs during development.
      The present study was designed to determine the expression pattern of snx3 mRNA,
      particularly in the mouse central nervous system (CNS), from the embryonic stage
      to adulthood. Whole mount in situ hybridization of embryonic day (E) 9.5 and 10.5
      mouse embryos revealed strong positive signals for snx3 mRNA in the forebrain,
      pharyngeal arches, eyes, and limb buds. In situ hybridization analyses of
      embryonic and neonatal brain sections revealed that snx3 mRNA is mainly expressed
      in the cerebral cortex, hippocampus, piriform cortex, cerebellum, and spinal
      cord. In adulthood, the expression of snx3 mRNA is observed in the cerebral
      cortex, hippocampus, piriform cortex, and cerebellar neurons. Thus, snx3 mRNA is
      expressed during neural development and in adult neural tissues, suggesting that
      SNX3 may play an important role in the development and function of the CNS.

PMID- 20817027
TI  - A preformed scleral search coil for measuring mouse eye movements.
AB  - Mice are excellent subjects for use of genetic-manipulation techniques to study
      the basis of pathological and normal physiology and behavior; however behavioral
      analyses of associated phenotypes is often limited. To improve the accuracy and
      specificity of repeated measurements of vestibular function, we developed a
      miniaturized, contact-lens scleral search coil to measure mouse eye movements. We
      describe the physical attributes and document its functionality by measuring
      vestibuloocular responses in normal mice. This coil should greatly improve the
      sensitivity and documentation of vestibular dysfunction in mouse models of
      pathology and dysfunction while allowing screening of significant numbers of
      subjects.

PMID- 20817028
TI  - Comparative evaluation of hypoxic-ischemic brain injury by flow cytometric
      analysis of mitochondrial membrane potential with JC-1 in neonatal rats.
AB  - We assessed the validity of monitoring changes in mitochondrial membrane
      potential (DeltaPsi) with a fluorescent probe, JC-1 (5,5',6,6'-tetrachloro
      1,1',3,3'-tetraethyl benzimidazolo-carbocyanine iodide), for the quantitative
      evaluation of neonatal hypoxic-ischemic brain injury. Seven-day-old rat pups were
      subjected to 2h of 8% oxygen following unilateral carotid artery ligation. Brain
      tissue was obtained for JC-1 staining at 24h after hypoxia ischemia (HI), and the
      results were compared with those of other simultaneous measurements such as flow
      cytometry with fluoresceinated annexin V/propidium iodide (PI), terminal
      deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL) staining,
      triphenyl tetrazolium chloride (TTC) infarct area and western blot for cytosolic
      cytochrome c. Flow cytograms of JC-1 showed two distinct sub-populations with
      different DeltaPsi, red with high DeltaPsi and green with low DeltaPsi, at 24h
      after HI. This shift of JC-1 fluorescence from red to green indicated a collapse
      of DeltaPsi. The increased percentage of low DeltaPsi with JC-1 showed a
      significant positive correlation with a simultaneous increase in annexin
      V(+)/PI(+) necrotic cells, TUNEL-positive cells, TTC infarct area and western
      blot of cytosolic cytochrome c, and negative correlation with annexin V(-)/PI(-)
      live cells. In summary, low DeltaPsi measured with JC-1 was significantly
      correlated with results from other methods used to assess the extent of brain
      damage after HI. Therefore, fluorocytometric analysis of DeltaPsi with JC-1 might
      be a sensitive and reliable technique in the quantitative evaluation of neonatal
      brain injury.

PMID- 20817030
TI  - Chimera construction using multiple-template-based sequential PCRs.
AB  - Chimera construction between different proteins is a useful method for
      investigating protein structure and function relationships. However, this
      technique, by its traditional application, has been daunting because of its
      complex procedure and low success rate. Here we describe a protocol for
      constructing chimeras between proteins that does not require the existence of
      restriction sites, or the purification of intermediate PCR products, which are
      essential in the traditional protocols. By introducing the "multiple-template"
      concept, this protocol only requires the use of two or three simple PCRs followed
      by general subcloning steps. Most importantly, the success rate is nearly 100%.

PMID- 20817029
TI  - A method for measuring brain partial pressure of oxygen in unanesthetized
      unrestrained subjects: the effect of acute and chronic hypoxia on brain tissue
      PO(2).
AB  - The level of tissue oxygenation provides information related to the balance
      between oxygen delivery, oxygen utilization, tissue reactivity and morphology
      during physiological conditions. Tissue partial pressure of oxygen (PtO(2)) is
      influenced by the use of anesthesia or restraint. These factors may impact the
      absolute level of PtO(2). In this study we present a novel fiber optic method to
      measure brain PtO(2). This method can be used in unanesthetized, unrestrained
      animals, provides absolute values for PO(2), has a stable calibration, does not
      consume oxygen and is MRI compatible. Brain PtO(2) was studied during acute
      hypoxia, as well as before and after 28 days of high altitude acclimatization. A
      sensor was chronically implanted in the frontal cortex of eight Wistar rats. It
      is comprised of a fiber optic probe with a tip containing material that
      fluoresces with an oxygen dependent lifetime. Brain PtO(2) declines by 80% and
      76% pre- and post-acclimatization, respectively, when the fraction of inspired
      oxygen declines from 0.21 to 0.08. In addition, a linear relationship between
      brain PtO(2) and inspired O(2) levels was demonstrated r(2)=0.98 and r(2)=0.99
      (pre- and post-acclimatization). Hypoxia acclimatization resulted in an increase
      in the overall brain PtO(2) by approximately 35%. This paper demonstrates the use
      of a novel chronically implanted fiber optic based sensor for measuring absolute
      PtO(2). It shows a very strong linear relationship in awake animals between
      inspired O(2) and tissue O(2), and shows that there is a proportional increase in
      PtO(2) over a range of inspired values after exposure to chronic hypoxia.

PMID- 20817031
TI  - An experimental model of focal ischemia using an internal carotid artery
      approach.
AB  - Animal models of cerebral ischemia represent an important contribution to both
      our understanding of stroke mechanism and the development of new therapies. The
      technique of MCAO (middle cerebral artery occlusion) via ECA (external carotid
      artery) occlusion is widely utilized. Disruption of the ECA and its branches
      leads to impaired mastication and oral intake, post-surgical body weight loss,
      and poor neurological recovery which can possibly confound one's interpretation
      of rats' neurological outcome. Here, we developed a novel modified technique for
      MCAO without ligation or coagulation of the ECA and its branches using an
      approach via the internal carotid artery (ICA). In our modified technique, we
      perform an additional fixation of the filament in the ICA which improves the
      stability of the model and increases the homogeneity in stroke size. Compared
      with the original MCAO technique via the ECA, our modified technique via the ICA
      demonstrated decreased variability in the percent infarcted volume and brain
      edema, as well as a decreased mortality. Additionally, we observed that with our
      modified technique, rats gained more weight after surgery and there was less
      initial weight loss after the surgical preparation. Our new approach may serve as
      an effective model for stroke, and may lead to a better understanding of stoke
      pathophysiology and to the future development of new drugs and other
      neuroprotective agents.

PMID- 20817032
TI  - Retinoid supplementation of differentiating human neural progenitors and
      embryonic stem cells leads to enhanced neurogenesis in vitro.
AB  - Retinoids are important molecules involved in the development and homeostasis of
      the nervous system. As such, various retinoid derivatives are often found in
      culture media and supplement formulations to support the growth and maintenance
      of neural cells. However, all-trans-retinoic acid (ATRA) and its associated
      derivatives are light sensitive and are highly susceptible to isomerisation. This
      can lead to variability in retinoid concentrations and the nature of the retinoid
      species present in culture solutions which in turn can influence biological
      activity and introduce inconsistency. We have previously described the
      development of the synthetic retinoid derivative, EC23, as a chemically and light
      stable alternative that does not degrade and has biological activity similar to
      ATRA. In this study we demonstrate that the addition of exogenous retinoid can
      significantly enhance neuronal differentiation of both human neuroprogenitor and
      human embryonic stem cells. In the former, both ATRA and EC23 induced increased
      maturation and stabilisation of the axonal cytoskeleton. However, EC23 was
      particularly potent at lower nanomolar concentrations resulting in significantly
      greater neurogenesis than ATRA. In ES cells enhanced motor neuron marker
      expression was also detected in response to both retinoids when incorporated into
      an established protocol for neuronal differentiation. We propose that synthetic
      retinoid EC23 represents a valuable addition to the formulation of new and
      existing culture supplements to enhance neuronal differentiation whilst enabling
      improved consistency.

PMID- 20817033
TI  - A novel algorithm for optimal image thresholding of biological data.
AB  - With the proliferation of both in vivo and in vitro microscopy techniques in the
      neurosciences, increased attention has been placed on the development of image
      analysis techniques. As experiments can produce large numbers of high bit depth
      images, automated processing methods have become necessary for handling these
      data sets. Thresholding, whereby a high bit depth image is converted into a
      binary image in order to identify a feature of interest, is one such standard
      automated technique; but the method of selecting an appropriate threshold value
      is far from standard. We present a novel algorithm, maximum correlation
      thresholding (MCT), that thresholds images accurately and efficiently without
      relying on any assumptions of the statistics of the image. As MCT produces
      thresholded images that preserve the most salient elements in the image, the
      algorithm performs as well as a trained user on a range of neurobiological data
      and in a variety of noisy conditions or when preprocessing steps preceded the
      thresholding operation. Our method will thus allow neuroscientists to automate
      image thresholding using a robust, computationally efficient algorithm,
      ultimately aiding in accurate image quantification and analysis.

PMID- 20817034
TI  - A novel system for in vivo neprilysin gene delivery using a syringe electrode.
AB  - Existing methods for in vivo gene transfer are generally inefficient and have
      several technical problems. In the present study we aimed to develop a safe,
      simple and efficient gene-delivery system for in vivo therapeutic applications.
      We focused on delivery of a plasmid encoding human neprilysin (hNEP), an enzyme
      implicated in the degradation of toxic amyloid-beta (Abeta) peptide, with
      potential application in Alzheimer's disease therapy. We report the development
      of a syringe electrode device in which DNA is injected via one of the two
      syringes and DNA uptake is stimulated by application of a brief pulsed square
      wave electrical field between the two syringe needles. Using this device,
      purified plasmid DNA encoding hNEP was injected into hindlimb skeletal muscle of
      6-week-old KunMing mice and electrostimulation (50V/cm, 6 pulses, 20ms per pulse)
      was applied to the syringe needles. hNEP protein was detected in muscle, serum
      and brain of treated mice by western blotting and ELISA at 7, 14 and 30 days post
      transfer. Importantly, hNEP levels following DNA injection alone, but without
      electrostimulation, were barely above background. Only low levels of muscle
      damage were detected following DNA injection and electrotransfer. These results
      demonstrate that DNA delivery by the syringe electrode technique can give rise to
      efficient long-term expression of the encoded polypeptide, and that the
      electrotransfer protocol is essential for effective plasmid DNA uptake and
      expression. This technique provides a safe and efficient non-viral method for in
      vivo gene delivery with potential applications in both basic research and in gene
      therapy of neuronal disease.

PMID- 20817035
TI  - High content analysis of histone acetylation in human cells and tissues.
AB  - There is increasing demand for automated image analysis of cell nuclei to be
      fast, objective and informative. Here, we have developed a high content analysis
      method for quantifying histone acetylation within any given population of cells.
      To demonstrate the utility of this method we quantified the effect of valproic
      acid (VPA) on histone H3 acetylation levels in SK-N-SH cells, a human
      neuroblastomal cell line. VPA, commonly used for treatment of bipolar disorder
      and epilepsy, has also been shown to act as a histone deacetylase inhibitor
      (HDACi), and to maintain the N-terminals of susceptible histones in an acetylated
      and transcriptionally active state. The Discovery-1TM (Molecular Devices)
      platform was used for automated image acquisition of immunolabelled cells.
      Multiple parameters of labelled nuclei were analysed in 1.82 s per image using
      the built-in count nuclei assay from MetaMorphTM (Molecular Devices) image
      analysis software. Data were presented in two forms: summary graphs or
      heterogeneity profiles using frequency distributions within GraphPad Prism
      (SmartDrawNet). Results showed that VPA increased histone H3 acetylation in a
      concentration- and time-dependent manner in SK-N-SH cells. The same analysis was
      shown to accurately quantify histone acetylation changes in human tissue sections
      also. Trichostatin A, a known HDACi was used to validate VPA action. Western
      blotting was used to validate the specificity of the antibodies. Overall these
      data demonstrate that this novel method for quantifying average treatment effects
      and the heterogeneity within any given population of cells, is fast, reproducible
      and can be applied to many different cellular contexts (immunocyto- and
      immunohisto-chemistry).

PMID- 20817036
TI  - Epileptic seizure detection using multiwavelet transform based approximate
      entropy and artificial neural networks.
AB  - Epilepsy is the most prevalent neurological disorder in humans after stroke.
      Recurrent seizure is the main characteristic of the epilepsy.
      Electroencephalogram (EEG) is the recording of brain electrical activity and it
      contains valuable information related to the different physiological states of
      the brain. Thus, EEG is considered an indispensable tool for diagnosing epilepsy
      in clinic applications. Since epileptic seizures occur irregularly and
      unpredictably, automatic seizure detection in EEG recordings is highly required.
      Multiwavelets, which contain several scaling and wavelet functions, offer
      orthogonality, symmetry and short support simultaneously, which is not possible
      for scalar wavelet. With these properties, recently multiwavelets have become
      promising in signal processing applications. Approximate entropy is a measure
      that quantifies the complexity or irregularity of the signal. This paper presents
      a novel method for automatic epileptic seizure detection, which uses approximate
      entropy features derived from multiwavelet transform and combines with an
      artificial neural network to classify the EEG signals regarding the existence or
      absence of seizure. To the best knowledge of the authors, there exists no similar
      work in the literature. A well-known public dataset was used to evaluate the
      proposed method. The high accuracy obtained for two different classification
      problems verified the success of the method.

PMID- 20817037
TI  - Characterization of the bout durations of sleep and wakefulness.
AB  - STUDY OBJECTIVES: (a) Develop a new statistical approach to describe the
      microarchitecture of wakefulness and sleep in mice; (b) evaluate differences
      among inbred strains in this microarchitecture; (c) compare results when data are
      scored in 4-s versus 10-s epochs. DESIGN: Studies in male mice of four inbred
      strains: AJ, C57BL/6, DBA and PWD. EEG/EMG were recorded for 24h and scored
      independently in 4-s and 10-s epochs. MEASUREMENTS AND RESULTS: Distribution of
      bout durations of wakefulness, NREM and REM sleep in mice has two distinct
      components, i.e., short and longer bouts. This is described as a spike (short
      bouts) and slab (longer bouts) distribution, a particular type of mixture model.
      The distribution in any state depends on the state the mouse is transitioning
      from and can be characterized by three parameters: the number of such bouts
      conditional on the previous state, the size of the spike, and the average length
      of the slab. While conventional statistics such as time spent in state, average
      bout duration, and number of bouts show some differences between inbred strains,
      this new statistical approach reveals more major differences. The major
      difference between strains is their ability to sustain long bouts of NREM sleep
      or wakefulness. Scoring mouse sleep/wake in 4-s epochs offered little new
      information when using conventional metrics but did when evaluating the
      microarchitecture based on this new approach. CONCLUSIONS: Standard statistical
      approaches do not adequately characterize the microarchitecture of mouse
      behavioral state. Approaches based on a spike-and-slab provide a quantitative
      description.

PMID- 20817038
TI  - A novel animal model of graded neuropathic pain: utility to investigate
      mechanisms of population heterogeneity.
AB  - The mechanisms underlying neuropathic pain are not well understood, resulting in
      unsatisfactory treatment outcomes for many patients. Animal models underpin much
      of the current understanding of pain mechanisms due to their perceived ability to
      mimic pain hypersensitivities; however, are limited by their binomial approach
      (pain vs. control), which does not reflect the clinical heterogeneity in
      nociceptive hypersensitivity. We modified the chronic constriction injury model
      by varying the number of sciatic nerve chromic gut sutures. Each Sprague Dawley
      rat received 4 pieces of chromic gut to control for the inflammatory challenge
      posed by the gut. Treatment groups were neuronal sutures (N), subcutaneous
      sutures (S) N0S0, N0S4, N1S3, N2S2 and N4S0. At postoperative (PO) day 29, there
      was a 'dose-response' relationship between the number of perineural sutures and
      von Frey threshold (N0S4<N1S3<N2S2<N4S0, P<0.05). This graded model was applied
      to investigate lumbar dorsal spinal cord glial activation marker expression.
      Microglial CD11b expression was positively correlated with graded allodynia in
      the ipsilateral dorsal horn (P<0.05, r(2)>0.9) and associated in the dorsolateral
      funiculus (DLF; P=0.10, r(2)>0.8) at PO day 14. Astrocyte GFAP expression was
      positively associated with graded allodynia in the ipsilateral dorsal horn
      (P=0.18, r(2)>0.6) and ipsilateral DLF (P<0.05, r(2)>0.9). DLF glial activation
      may represent a contributor to contralateral pain. Our novel graded model has a
      dynamic range, allowing sensitive detection of interactions and subtle influences
      on neuropathic pain processing.

PMID- 20817039
TI  - Tracking brain dynamics via time-dependent network analysis.
AB  - Complex network analysis is currently employed in neuroscience research to
      describe the neuron pathways in the brain with a small number of computable
      measures that have neurobiological meaning. Connections in biological neural
      networks might fluctuate over time; therefore, surveillance can provide a more
      useful picture of brain dynamics than the standard approach that relies on a
      static graph to represent functional connectivity. Using the application of well
      known measures of neural synchrony over short segments of brain activity in a
      time series, we attempted a time-dependent characterization of brain connectivity
      by investigating functional segregation and integration. In our implementation, a
      frequency-dependent time window was employed and regularly spaced (defined as
      overlapping segments), and a novel, parameter-free method was introduced to
      derive the required adjacency matrices. The resulting characterization was
      compared against conventional approaches that rely on static and time-evolving
      graphs, which are constructed from non-overlapping segments of arbitrarily
      defined durations. Our approach is demonstrated using EEG recordings during
      mental calculations. The derived consecutive values of network metrics were then
      compared with values from randomized networks. The results revealed the dynamic
      small-world character of the brain's functional connectivity, which otherwise can
      be hidden from estimators that rely on either long or stringent time-windows.
      Moreover, by involving a network-metric time series (NMTS) in a summarizing
      procedure that was based on replicator dynamics, consistent hubs that facilitated
      communication in the underlying networks were identified. Finally, the scale-free
      character of brain networks was also demonstrated based on the significant edges
      selected with the introduced approach.

PMID- 20817040
TI  - Evolution and world-wide distribution of varicella-zoster virus clades.
AB  - Varicella-zoster virus (VZV, Human herpesvirus 3), a world-wide distributed
      pathogen, is the causative agent of varicella (chickenpox) and zoster (shingles).
      Both diseases result in significant morbidity and economic burden. The
      implementation of routine varicella vaccination programs in many countries may
      reduce significantly the incidence of varicella disease. Furthermore, vaccination
      against zoster can diminish the burden of zoster considerably. Although many
      epidemiological, clinical and laboratory studies were performed in the past
      decades to reveal the clinical burden as well as epidemiological features and
      changes of the two diseases caused by VZV, a comparatively low number of
      molecular epidemiological studies have been performed to investigate and monitor
      the genetic variability and phylogenetic relationship of VZV strains throughout
      the world. To date, it is well established that VZV can be divided into five
      major clades confirmed by full-genome sequencing and two provisional clades that
      have to be confirmed. Additionally, several studies have demonstrated a regional
      dominance of specific VZV clades, most likely in dependence on environmental
      factors, evolutionary conditions and host-virus interactions and/or importation
      of viral strains. However, there are many open questions such as the alteration
      of genotype distribution through immigration or travel, the introduction of the
      varicella vaccine strain into population and the emergence of wild-type vaccine
      recombinant viruses. To increase our knowledge in this field by further
      innovative approaches, the new common nomenclature of VZV clades established
      recently will be very useful. In this review, the currently available data
      concerning the geographic distribution and evolution of VZV clades are
      summarized. Different models of VZV evolution and recombination are discussed and
      recent changes in VZV clade distribution addressed.

PMID- 20817041
TI  - Disruptive effect of amphetamines on Pavlovian to instrumental transfer.
AB  - Reward-seeking behavior can be powerfully modulated by exposure to a conditioned
      stimulus (CS) that was previously associated with that reward. This can be
      demonstrated in a Pavlovian to instrumental transfer (PIT) task where
      presentation of a CS (e.g., tone and light) previously paired with a rewarding
      unconditioned stimulus (US; e.g., food) leads to increases in a behavioral
      response, such as a lever press, that was also paired with the same US. The
      transfer effect can be enhanced in rats by exposing them repeatedly to
      amphetamine after they have undergone Pavlovian conditioning and instrumental
      training. However, it is not clear if amphetamine injections given immediately
      after Pavlovian conditioning, which are predicted to enhance memory consolidation
      for the CS-US association, would also enhance the transfer effect. We tested this
      hypothesis by giving male, Sprague-Dawley rats i.p. injections of saline or drug
      (0.5, 1.0, or 3.0 mg/kg amphetamine or methamphetamine) immediately following
      Pavlovian conditioning sessions. We found that amphetamine, but not
      methamphetamine, enhanced Pavlovian approach behavior. During a subsequent PIT
      test done under extinction conditions, we found that rats given either drug,
      particularly at the highest dose, exhibited deficits in PIT relative to saline
      treated controls. These results suggest that treatment with amphetamines after
      Pavlovian conditioning sessions, when memory consolidation of the CS-US
      association is hypothesized to occur, inhibits the ability of the CS to
      subsequently elicit reward-seeking behavior.

PMID- 20817042
TI  - Increment of hypothalamic 2-arachidonoylglycerol induces the preference for a
      high-fat diet via activation of cannabinoid 1 receptors.
AB  - The aim of the present study is to examine the relationship between preference
      for HFD and 2-arachidonoylglycerol (2-AG), endogenous cannabinoid. The 3-day HFD
      intake induced preference for HFD, which was suppressed by CB1 antagonist, O
      2050. Moreover, hypothalamic 2-AG was increased after 3-day HFD intake. Our
      results show that preference for HFD is induced by activation of CB1 receptors
      via an increment of 2-AG in hypothalamus.

PMID- 20817045
TI  - Alzheimer's disease: effects of beta-amyloid on mitochondria.
AB  - The impairment of the respiratory chain or defects in the detoxification system
      can decrease electron transfer efficiency, reduce ATP production, and increase
      reactive oxygen species (ROS) production by mitochondria. Accumulation of ROS
      results in oxidative stress, a hallmark of neurodegenerative diseases such as
      Alzheimer's disease (AD). beta-amyloid has been implicated in the pathogenesis of
      AD, and its accumulation may lead to degeneration of neuronal or non-neuronal
      cells. There is evidence that beta-amyloid interacts with mitochondria but little
      is known concerning the significance of this interaction in the physiopathology
      of AD. This review explores possible mechanisms of beta-amyloid-induced
      mitochondrial toxicity.

PMID- 20817043
TI  - Dopamine transporter genotype predicts implicit sequence learning.
AB  - Implicit learning, the non-conscious acquisition of sequential and spatial
      environmental regularities, underlies skills such as language, social intuition,
      or detecting a target in a complex scene. We examined relationships between a
      variation of the dopamine transporter (DAT1) gene (SLC6A3), which influences
      dopamine transporter expression in the striatum, and two forms of implicit
      learning that differ in the regularity to be learned and in striatal involvement.
      Participants, grouped as 9-repeat carriers or 10/10 homozygotes, completed the
      triplets learning task (TLT) and the spatial contextual cueing task (SCCT). The
      TLT assesses sequence learning, recruiting the striatal system, particularly as
      training continues. In contrast, the SCCT assesses spatial context learning,
      recruiting medial temporal brain networks. For both tasks, participants
      demonstrated learning in faster and/or more accurate responses to repeating
      patterns or spatial arrays. As predicted, TLT learning was greater for the 9
      repeat carriers than the 10/10 group (despite equal overall accuracy and response
      speed) whereas there were no significant group differences in SCCT. Thus,
      presence of the DAT1 9-repeat allele was beneficial only for implicit sequence
      learning, indicating the influence of DAT1 genotype on one form of implicit
      learning and supporting evidence that implicit learning of sequential
      dependencies and spatial layouts recruit different neural systems.

PMID- 20817044
TI  - Alterations in adult behavioral responses to cocaine and dopamine transporters
      following juvenile exposure to methamphetamine.
AB  - The present experiment assessed whether preadolescent exposure to methamphetamine
      would alter adult behavioral responses to cocaine and dopamine transporter
      immunoreactivity in the striatum of male and female rats. Juvenile rats were
      injected once daily with 0 or 2 mg/kg methamphetamine from postnatal days 21 to
      35 and tested in adulthood. Male rats, but not female rats, exposed to
      methamphetamine showed an increase in responsiveness to cocaine in the open field
      and an increase in dopamine transporter immunoreactivity in the striatum. These
      findings suggest that early exposure to methamphetamine can lead to sex specific
      altered responses to psychostimulants in adulthood, which may contribute to later
      vulnerability to drug use.

PMID- 20817046
TI  - Acquired coenzyme Q10 deficiency in children with recurrent food intolerance and
      allergies.
AB  - The current study evaluated 23 children (ages 2-16 years) with recurrent food
      intolerance and allergies for CoQ10 deficiency and mitochondrial abnormalities.
      Muscle biopsies were tested for CoQ10 levels, pathology, and mitochondrial
      respiratory chain (MRC) activities. Group 2 (age >10 years; n = 9) subjects had
      significantly decreased muscle CoQ10 than Group 1 (age <10 y; n = 14) subjects (p
      = 0.001) and 16 controls (p<0.05). MRC activities were significantly lower in
      Group 2 than in Group 1 (p<0.05). Muscle CoQ10 levels in study subjects were
      significantly correlated with duration of illness (adjusted r(2) = 0.69; p =
      0.012; n = 23). Children with recurrent food intolerance and allergies may
      acquire CoQ10 deficiency with disease progression.

PMID- 20817047
TI  - Age related changes in mitochondrial function and new approaches to study redox
      regulation in mammalian oocytes in response to age or maturation conditions.
AB  - Mammalian oocytes are long-lived cells in the human body. They initiate meiosis
      already in the embryonic ovary, arrest meiotically for long periods in dictyate
      stage, and resume meiosis only after extensive growth and a surge of luteinizing
      hormone which mediates signaling events that overcome meiotic arrest. Few
      mitochondria are initially present in the primordial germ cells while there are
      mitogenesis and structural and functional differentiation and stage-specific
      formation of functionally diverse domains of mitochondria during oogenesis.
      Mitochondria are most prominent cell organelles in oocytes and their activities
      appear essential for normal spindle formation and chromosome segregation, and
      they are one of the most important maternal contributions to early embryogenesis.
      Dysfunctional mitochondria are discussed as major factor in predisposition to
      chromosomal nondisjunction during first and second meiotic division and mitotic
      errors in embryos, and in reduced quality and developmental potential of aged
      oocytes and embryos. Several lines of evidence suggest that damage by oxidative
      stress/reactive oxygen species in dependence of age, altered antioxidative
      defence and/or altered environment and bi-directional signaling between oocyte
      and the somatic cells in the follicle contribute to reduced quality of oocytes
      and blocked or aberrant development of embryos after fertilization. The review
      provides an overview of mitogenesis during oogenesis and some recent data on
      oxidative defence systems in mammalian oocytes, and on age-related changes as
      well as novel approaches to study redox regulation in mitochondria and ooplasm.
      The latter may provide new insights into age-, environment- and cryopreservation
      induced stress and mitochondrial dysfunction in oocytes and embryos.

PMID- 20817048
TI  - Microarray analyses of mouse responses to infection by Neospora caninum
      identifies disease associated cellular pathways in the host response.
AB  - Neospora caninum is a coccidian cyst-forming parasite found in a wide range of
      host species such as mice, dogs and cattle. The development of methods such as
      vaccines to prevent abortion and fetal loss due to neosporosis would be greatly
      assisted by further knowledge on immunity and host responses to infection. In
      this study we used microarray technology to investigate the protective host
      responses occurring at 6h post infection in the spleen of mice infected with a
      prototype live N. caninum vaccine. Naive non-pregnant mice were infected with the
      NC-Nowra isolate as such infections are known to induce protective host responses
      that will prevent transplacental transmission of a challenge given using
      pregnancy. The expression data was analysed by SAM (significance of microarrays),
      ANOVA and clustering methods. Gene lists were investigated for enrichment of gene
      ontology terms by functional annotation using hypergeometric tests. The results
      show that Qs and BALB/c mice infected with NC-Nowra differ in their
      transcriptional responses to infection and these affect a wide range of
      biological and molecular processes. Transcriptional changes in the Jak-STAT
      signaling pathway (as well as Irf and other IFN-gamma regulated molecules such as
      GTPases) confirmed the influence of IFN-gamma in the mouse response to N.
      caninum. Gene ontology analyses also assigned some of the molecules involved to
      well known disease pathways associated with cancer, Parkinson's and Alzheimer's
      diseases, which were linked to the cell cycle, mitochondrial electron transport
      chain and coupled proton transport pathways amongst others. Although infection of
      mice with NC-Nowra causes little or no signs of clinical disease, the molecular
      functions, processes and pathways identified through these studies clearly
      warrant further investigation for their role in the development of protective
      immunity as well as pathogenesis. These studies therefore provide new, exciting
      leads by which to study neosporosis.

PMID- 20817049
TI  - General surgical adverse events in a UK district general hospital-lessons to
      learn.
AB  - BACKGROUND: An adverse event (AE) is defined as an unintended injury or
      complication caused by healthcare management rather than the disease process that
      may prolong admission and lead to disability or death. This study retrospectively
      assessed all reported general surgery-related AEs in a district general hospital
      in the south-east of England. METHODS: All general surgical AEs arising from
      adult inpatient admissions between 2002 and 2007, that had been reported to the
      risk management team, following completion of the standard 'Adverse Incident
      Report Form', were retrospectively reviewed. RESULTS: There were 24,185 general
      surgical admissions over the period of the study; 461 AEs were reported (1.9%
      mean annual incident rate; 95% CI, 1.3%-2.5%). The majority (85%) were near miss
      or no injury events (category I and II) while serious/serious near-miss incidents
      accounted for just 2% of events. Communicative or administrative problems were
      implicated in 54% of cases while 12% arose from theatre/surgery-related failure.
      Of 58 medico-legal claims (0.24% of admissions) that were made, 16 (27.5%)
      progressed to the law courts for formal settlement. CONCLUSION: The reported
      annual AE incident rate of approximately 2% is well below the national average:
      this may be due to pre-selection of general surgery-related AEs or represent
      under-reporting of incidents. The vast majority of AEs were related to
      administrative and communicative error. These areas must be addressed if patient
      safety and outcome is to be significantly improved.

PMID- 20817050
TI  - Size exclusion chromatography: an improved method to harvest Corynebacterium
      glutamicum cells for the analysis of cytosolic metabolites.
AB  - The efficient separation of Corynebacterium glutamicum cells from culture medium
      by size exclusion chromatography (SEC) is presented. Residue analysis
      demonstrated that this method effectively depletes extracellular compounds. For
      evaluation, SEC was compared with the common methods cold methanol treatment,
      fast centrifugation and fast filtration. For this purpose, samples of C.
      glutamicum cells from fermenter cultures were harvested and subjected to a
      metabolome analysis. In particular, the wild type strain C. glutamicum ATCC13032
      and the lysine production strain C. glutamicum DM1730 were grown in a minimal or
      in a complex medium. Comparison of metabolite pool sizes after harvesting C.
      glutamicum cells by the methods mentioned above by gas chromatography coupled to
      mass spectrometry (GC-MS) revealed that SEC is the most suitable method when
      intracellular metabolite pools are to be measured during growth in complex media
      or in the presence of significant amounts of secreted metabolites. In contrast to
      the other methods tested, the SEC method turned out to be fast and able to remove
      extracellular compounds almost completely.

PMID- 20817052
TI  - BoneJ: Free and extensible bone image analysis in ImageJ.
AB  - Bone geometry is commonly measured on computed tomographic (CT) and X-ray
      microtomographic (MUCT) images. We obtained hundreds of CT, MUCT and synchrotron
      MUCT images of bones from diverse species that needed to be analysed remote from
      scanning hardware, but found that available software solutions were expensive,
      inflexible or methodologically opaque. We implemented standard bone measurements
      in a novel ImageJ plugin, BoneJ, with which we analysed trabecular bone, whole
      bones and osteocyte lacunae. BoneJ is open source and free for anyone to
      download, use, modify and distribute.

PMID- 20817051
TI  - Hypoxia increases Annexin A2 expression in osteoblastic cells via VEGF and ERK.
AB  - Vascular endothelial growth factor (VEGF)-stimulated angiogenesis is critical for
      endochondral ossification that occurs during bone development and bone repair.
      Under these circumstances, VEGF production appears to be driven by low oxygen
      tension, under the control of the hypoxia-inducible factor-alpha family of
      transcription factors (HIF-alpha). Annexin 2 (AnxA2) a calcium-dependent
      phospholipid binding protein has been implicated in VEGF-mediated retinal
      neovascularization and is upregulated by VEGF in choroid retinal endothelial
      cells. AnxA2 is also expressed in cells of the osteoblast lineage and
      chondrocytes and may play a role in matrix mineralization. In this paper, we
      examined the effects of hypoxia (1% O(2)) and VEGF on the expression of AnxA2 in
      osteoblastic MC3T3-E1 cells. Hypoxia, desferrioxamine (hypoxia mimetic), and
      recombinant VEGF all increased AnxA2 mRNA and protein levels in osteoblastic
      cells. The hypoxia-induced increase in AnxA2 was inhibited by a blocking antibody
      to VEGF-R1; however, VEGF(120), a VEGF-R1 agonist, demonstrated no influence upon
      Anxa2 expression. This suggests that VEGF induction of Annexin A2 is not mediated
      via VEGF-R1 agonism alone but by VEGF-R1 and Neuropilin-1 or Neuropilin-2
      heterodimers. In addition, we demonstrated that VEGF-stimulated changes in AnxA2
      expression via a pathway involving Src and MEK kinase. These data demonstrate
      that AnxA2 expression in osteoblasts is under the control of VEGF, which may have
      implications for both angiogenesis and bone mineralization under low oxygen
      conditions.

PMID- 20817053
TI  - Strontium ranelate and risk of vertebral fractures in frail osteoporotic women.
AB  - AIM: Therapies to treat osteoporosis remain underutilized and minimally evaluated
      in frail elderly patients. Our study determined and compared the risk of
      vertebral fractures in frail, intermediate and robust older patients being
      treated with strontium ranelate vs. placebo. METHODS: Data were obtained from the
      SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (Treatment Of
      Peripheral Osteoporosis) studies which randomized participants to receive either
      strontium ranelate or placebo over 3 years. Frail, intermediate and robust
      patients were identified using adapted Fried's criteria. Analyses were performed
      according to the intention-to-treat principle utilizing 1- and 3-year study
      follow-up data. RESULTS: 2346 robust, 2472 intermediate and 264 frail women were
      identified. At 3 years, the risk for vertebral fractures was reduced by 30%
      (Relative Risk [RR], 0.70; 95% confidence interval [CI], 0.57-0.86) in the
      robust, by 45% (RR, 0.55; 95%CI, 0.46-0.67) in the intermediate and by 58% (RR,
      0.42; 95%CI, 0.24-0.74) in the frail patients compared to those assigned to
      placebo (p<0.01 for all three groups; p=0.11 for trend). Risk of vertebral
      fracture was significantly reduced within 1 year in all three groups. Numbers of
      subjects needed to be treated to prevent one new vertebral fracture over 3 years
      were 13, 9 and 5 in the robust, intermediate and frail groups, respectively.
      Adverse event profiles and medication compliance were similar across the 3
      groups. CONCLUSIONS: The imperative to treat osteoporosis appears to be greatest
      in frail patients since similar relative risk reductions would avert more
      fractures in frail than in non-frail elderly patients.

PMID- 20817054
TI  - Targeting antigens to an invariant epitope of the MHC Class II DR molecule
      potentiates the immune response to subunit vaccines.
AB  - Recombinant subunit and peptidic vaccines in general present a reduced
      immunogenicity in vaccinated individuals with respect to the whole pathogen from
      which they derived. The generation of strong immune responses to these vaccines
      requires the use of potent adjuvants, high antigen doses and repetitive
      vaccinations. In this report, we document the enhanced antibody response obtained
      against two recombinant subunit vaccines by means of targeting to antigen
      presenting cells by a recombinant single chain antibody. This antibody, named
      APCH1, recognizes an epitope of MHC Class II DR molecule preserved in different
      animal species, including humans. We showed that vaccinal antigens
      translationally fused to APCH1 antibody and produced by recombinant baculoviruses
      in insect larvae (Trichoplusia ni), elicited an increased antibody response in
      comparison with the same antigens alone or fused to a carrier molecule. These
      results suggest that targeting of antigens to this invariant MHC Class II epitope
      has immunopotentiating effects that could circumvent the reduced potency of
      peptidic or subunit vaccines, opening the possibility of widespread application
      of APCH1 as a new adjuvant antibody of general use.

PMID- 20817055
TI  - The Bombyx mori nucleopolyhedrovirus (BmNPV) ODV-E56 envelope protein is also a
      per os infectivity factor.
AB  - The Bombyx mori nucleopolyhedrovirus (BmNPV) odv-e56 gene is a late gene and
      encodes an occlusion-derived virus (ODV)-specific envelope protein, ODV-E56. To
      determine its role in the BmNPV life cycle, an odv-e56 null virus, BmE56D, was
      constructed through homologous recombination. A repaired virus was also
      constructed, named BmE56DR. The production of budded virion (BV) and polyhedra,
      the replication of viral DNA, and the morphological of infected BmN cells were
      analyzed, revealing no significant difference among the BmE56D, the wild-type
      (WT), and the BmE56DR virus. Larval bioassays demonstrated that injection of
      BmE56D BV into the hemocoel could kill B. mori larvae as efficiently as repaired
      and WT viruses, however BmE56D was unable to infect the B. mori larvae when
      inoculated per os. Thus, these results indicated that ODV-E56 envelope protein of
      BmNPV is also a per os infectivity factor (PIF), but is not essential for virus
      replication.

PMID- 20817056
TI  - Construction of an infectious cDNA clone for Omsk hemorrhagic fever virus, and
      characterization of mutations in NS2A and NS5.
AB  - Omsk hemorrhagic fever virus (OHFV) is a member of the tick-borne encephalitis
      serocomplex of flaviviruses, and causes hemorrhagic disease in humans. In this
      study, an infectious cDNA of OHFV was constructed to investigate the molecular
      mechanisms involved in OHFV pathogenesis for the first time. Our cDNA clone was
      capable of producing infectious virus which is genetically identical to the
      parental Guriev strain, and the recombinant virus showed similar biological
      properties to the parental virus including growth kinetics and virulence
      characteristics. While characterizing the cDNAs, fortuitous mutations at NS2A
      position 46 and NS5 position 836 were found to affect viral production. By using
      a viral replicon expressing luciferase, it was shown that both of the mutations
      produced a defect in RNA replication and that the NS5 mutation induced a
      temperature-sensitive phenotype, indicating the importance of these residues in
      RNA replication. This infectious cDNA will be a useful tool to study the
      replication and pathogenesis of OHFV.

PMID- 20817057
TI  - Molecular cloning, characterization and expression analysis of cathepsin A gene
      in Chinese mitten crab, Eriocheir sinensis.
AB  - Cathepsins, a superfamily of hydrolytic enzymes produced and enclosed within
      lysosomes, function in immune response in vertebrates; however, their function
      within the innate immune system of invertebrates remains largely unknown.
      Therefore, we investigated the immune functionality of cathepsin A (catA) in
      Chinese mitten crab (Eriocheir sinensis), a commercially important and disease
      vulnerable aquaculture species. The full length catA cDNA (2200 bp) was cloned
      via PCR based upon an initial expressed sequence tag (EST) isolated from a
      hepatopancreatic cDNA library. The catA cDNA contained a 1398 bp open reading
      frame (ORF) that encoded a putative 465 amino acid (aa) protein. Comparisons with
      other reported vertebrate cathepsins sequences revealed percent identity range
      from 48 to 51%. CatA mRNA expression in E. sinensis was (a) tissue-specific, with
      the highest expression observed in gill and (b) responsive in hemocytes to a
      Vibrio anguillarum challenge, with peak exposure observed 12 h post-injection.
      Collectively, data demonstrate the successful isolation of catA from the Chinese
      mitten crab, and its involvement in the innate immune system of an invertebrate.

PMID- 20817058
TI  - Insulin-induced gene: a new regulator in lipid metabolism.
AB  - Insulin-induced genes (Insigs) including Insig-1 and Insig-2, are proteins that
      mediate sterol regulation of sterol regulatory element-binding protein (SREBP)
      cleavage-activating protein (SCAP) and 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase (HMG-CoA reductase). Insigs perform distinct tasks in the regulation of
      these effectors: they promote the endoplasmic reticulum (ER) retention of SCAP,
      but ubiquitin-mediated degradation of HMG-CoA reductase. Through these
      activities, Insig-1 and Insig-2 influence cholesterol metabolism, lipogenesis,
      and glucose homeostasis in diverse tissues such as adipose tissue and liver. In
      this article, we focus on the functions, expression and regulation, gene
      polymorphisms of Insigs, and their deficiency with diseases.

PMID- 20817060
TI  - Rac1 activity changes are associated with neuronal pathology and spatial memory
      long-term recovery after global cerebral ischemia.
AB  - Excitotoxicity is the main event during neurological disorders producing drastic
      morphological and functional changes. Rac-GTPase is involved in cytoskeletal
      remodeling and survival. However, the role of Rac1 after cerebral ischemia has
      not been completely understood yet. In this study, we evaluated the activity of
      Rac1 and its immunoreactivity associated to neuropathological hallmarks and
      behavioral task analyses after global cerebral ischemia in an acute and long-term
      post-ischemia period. Our findings showed that during the acute phase (24h) after
      global cerebral ischemia, a decrease of the active state of Rac1 was detected in
      the hippocampus, together with a down-regulation of survival signaling. In this
      same post-ischemia time, Rac1 immunoreactivity was redistributed to cytoplasm and
      to aberrant neurites, accompanied by dendritic and actin cytoskeletal retraction
      both in vivo and in vitro in neuronal primary cultures treated with glutamate.
      Neurons transfected with the constitutively active mutant of Rac1 were recovered
      from the glutamate-induced affection in vitro. However, in the in vivo model an
      inactive state of Rac1, and its cellular localization remained one month after
      ischemia, with still decreased survival signaling, significant tauopathy, and
      learning and memory alterations. These neuropathological hallmarks were reversed
      two months post-ischemia, related with a Rac1 activity state similar to control,
      as well as a "normalization" of the learning and memory tasks in the ischemic
      rats. In summary, our data suggests that changes in Rac1 activity are involved in
      the neurodegenerative processes after cerebral ischemia, and also in its long
      term recovery.

PMID- 20817059
TI  - Cold ambient temperature reverses abdominal surgery-induced delayed gastric
      emptying and decreased plasma ghrelin levels in rats.
AB  - We investigated whether acute cold-induced vagal activation through brainstem
      thyrotropin-releasing hormone (TRH) signaling influences abdominal surgery
      induced delayed gastric emptying (GE) in fasted rats. Laparotomy and cecal
      palpation or sham (short anesthesia alone) was performed 10 min before or 30 min
      after cold exposure (4-6 degrees C) lasting 90 min. Non-nutrient GE was assessed
      during 70-90 min of cold exposure. Control groups remained at room temperature
      (RT). The stable TRH analog, RX-77368 (50 ng/rat) was injected intracisternally
      immediately before surgery and GE monitored 30-50 min postsurgery in rats
      maintained at RT. Plasma acyl (AG) and total ghrelin levels were assessed using
      the new RAPID blood processing method and radioimmunoassays. Desacyl ghrelin
      (DAG) was derived from total minus AG. In rats maintained at RT, abdominal
      surgery decreased GE by 60% compared to sham. Cold before or after surgery or RX
      77368 normalized the delayed GE. In non-fasted rats, cold exposure increased
      plasma AG and DAG levels at 2 h (2.4- and 2.7-times, respectively) and 4 h (2.2-
      and 2.0-times, respectively) compared to values in rats maintained at RT. In
      fasted rats, abdominal surgery decreased AG and DAG levels by 2.4- and 2.1-times,
      respectively, at 90 min. Cold for 90 min after surgery normalized AG and DAG
      levels to those observed in sham-treated animals kept at RT. These data indicate
      that endogenous (cold exposure) and exogenous (TRH analog) activation of
      medullary TRH vagal signaling prevent abdominal surgery-induced delayed GE. The
      restoration of circulating AG levels inhibited by abdominal surgery may
      contribute to alleviate postoperative gastric ileus.

PMID- 20817061
TI  - Prosurvival role of JAK/STAT and Akt signaling pathways in MPP+-induced apoptosis
      in neurons.
AB  - In the present study the role of JAK/STAT and Akt in apoptosis was evaluated in
      cerebellar granule cells after treatment with the mitochondrial toxin MPP(+).
      Firstly, we evaluated the role of the prosurvival Akt pathway in MPP(+)-induced
      apoptosis and found that MPP(+) rapidly reduced the phosphorylation of Akt at
      Ser473. Since PTEN is an upstream regulator of Akt, its inhibition with bpV(pic)
      (1-30 MUM) should activate Akt, however, it did not attenuate CGC cell death
      mediated by MPP(+) but protected CGC from apoptosis mediated by S/K deprivation.
      We also demonstrated that after the treatment with the complex I inhibitor, the
      expression levels of STAT1 increased and the levels of STAT3 decreased at the
      time points tested (0.5-8h). Meanwhile, pharmacological inhibition of the
      JAK/STAT pathway with AG490 (10-40 MUM) was neuroprotective, probably due to its
      antioxidant properties, the Jak2-inhibitor-II potentiated MPP(+) neurotoxicity.
      Collectively, our data indicate that the treatment of CGC with the neurotoxin
      MPP(+) decreased two prosurvival pathways: STAT3 and Akt. Meanwhile Akt
      activation, using a PTEN inhibitor, did not play a prominent role in
      neuroprotection; loss of STAT3 could be a signal pathway involved in
      neuroprotection against the Parkinsonian neurotoxin MPP(+).

PMID- 20817062
TI  - Temporal expression of P2X7 purinergic receptor during the course of experimental
      autoimmune encephalomyelitis.
AB  - Purinergic P2X(7) receptors are nucleotide-gated ion channels widely distributed
      in brain. Strong evidence suggests that they are involved in cross-talk between
      glial and neuronal cells. These receptors activated under pathological conditions
      may participate in regulation of inflammatory response and cell death. In this
      study we show the expression of P2X(7) protein and mRNA during the course of
      experimental autoimmune encephalomyelitis (EAE), an animal model of multiple
      sclerosis (MS), in different stages of the disease (4, 6, 8, 10 post
      immunization). The enhanced expression of the receptor at the level of both mRNA
      and protein was observed in the peak of neurological symptoms and was connected
      mostly with neurons. However, early overexpression of receptor protein was
      observed also in an asymptomatic phase of EAE and was tightly related to
      astrocytic pool of cells. This suggests the early involvement of this kind of
      receptor into pathological mechanisms leading for symptoms characteristic for
      EAE.

PMID- 20817063
TI  - Brain tryptophan rather than pH-value is altered as consequence of artificial
      postmortem interval and storage conditions.
AB  - Brain bank centers around the world attempt to standardize postmortem brain
      collection and quality control. Antemortem as well postmortem factors may
      influence tissue quality. Previously, we could demonstrate that increased
      tryptophan (TRP) levels significantly correlate to prolonged postmortem interval
      (PMI) and storage duration, whereas pH-value altered merely as consequence of
      prolonged agonal state and ischemic brain damage additionally to repeated freeze
      and thaw cycles. Therefore, we aimed to investigate in artificial PMI conditions,
      with three brain tissue storage temperatures (4 degrees C, room temperature and
      37 degrees C) as well as oxidizing conditions (open/close tube), whether TRP
      levels and pH-value alter. We could confirm that prolonged PMI at higher storage
      temperatures and oxidizing conditions significantly correlate to increased TRP
      levels, while pH-value did not correlate at all. In conclusion, from these
      results PMI intervals until autopsy should be kept as short as possible and
      storage until autopsy should be at 4 degrees C in order to preserve brain tissue
      quality as much as possible.

PMID- 20817064
TI  - Determining receptor-ligand interaction of human galanin receptor type 3.
AB  - Galanin is a neuropeptide found throughout the central and peripheral nervous
      systems of a wide range of species, ranging from human and mouse to frog and
      tuna. Galanin mediates its physiological roles through three receptors (GalR1-3),
      all members of the G-protein coupled receptor family. In mapping these roles,
      receptor subtype selective ligands are crucial tools. To facilitate the ligand
      design, data on receptor structure and interaction points are of great
      importance. The current study investigates the mechanism by which galanin
      interacts with GalR3. Mutated receptors were tested with competitive binding
      analysis in vitro. Our studies identify six mutagenic constructs that lost
      receptor affinity completely, despite being expressed at the cell surface.
      Mutations of the Tyr103(3.33) in transmembrane helix (TM) III, His251(6.51) in TM
      VI, Arg273(7.35) or His277(7.39) in TM VII, Phe263(6.63) or Tyr270(7.32) in the
      extracellular loop III all result in complete reduction of ligand binding. In
      addition, docking studies of an in silico model of GalR3 propose that four of the
      identified residues interact with pharmacophores situated within the galanin(2-6)
      sequence. This study provides novel insights into the interaction between ligands
      and GalR3 and highlights the requirement for correct design of targeting ligands.

PMID- 20817065
TI  - Glutamate regulates eEF1A phosphorylation and ribosomal transit time in Bergmann
      glial cells.
AB  - Glutamate, the major excitatory transmitter in the vertebrate brain, is involved
      in neuronal development and synaptic plasticity. Glutamatergic stimulation leads
      to differential gene expression patterns in neuronal and glial cells. A glutamate
      dependent transcriptional control has been established for several genes.
      However, much less is known about the molecular events that modify the
      translational machinery upon exposure to this neurotransmitter. In a glial model
      of cerebellar cultured Bergmann cells, glutamate induces a biphasic effect on
      [(35)S]-methionine incorporation into proteins that suggests that the elongation
      phase of protein biosynthesis is the target for regulation. Indeed, after a 15
      min exposure to glutamate a transient increase in elongation factor 2
      phosphorylation has been reported, an effect mediated through the activation of
      the elongation factor 2 kinase. In this contribution, we sought to characterize
      the phosphorylation status of the eukaryotic elongation factor 1A (eEF1A) and the
      ribosomal transit time under glutamate exposure. A dose-dependent increase in
      eEF1A phosphorylation was found after a 60 min glutamate treatment; this
      phenomenon is Ca(2+)/CaM dependent, blocked with Src and phosphatidyl-inositol 3
      kinase inhibitors and with rapamicyn. Concomitantly, the ribosomal transit time
      was increased with a 15 min glutamate exposure. After 60 more minutes, the
      average time used by the ribosomes to complete a polypeptide chain had almost
      returned to its initial level. These results strongly suggest that glutamate
      exerts an exquisite time-dependent translational control in glial cells, a
      process that might be critical for glia-neuron interactions.

PMID- 20817066
TI  - alpha7 nicotinic receptor agonism mitigates phencyclidine-induced changes in
      synaptophysin and Arc gene expression in the mouse prefrontal cortex.
AB  - Repeated phencyclidine (PCP) administration in mice reproduces several
      histopathological features of schizophrenia, such as reduced synaptophysin and
      parvalbumin mRNA expression in the frontal cortex. These changes can be prevented
      by co-administering the alpha7 nicotinic acetylcholine receptor (nAChR) agonist
      SSR180711 with PCP, but it is not known to what extent PCP-induced changes can be
      normalized once they have already occurred. Here we use semi-quantitative in situ
      hybridization to show that repeated administration of SSR180711 (3 mg/kg b.i.d.
      for 5 days) subsequent to repeated PCP administration (10 mg/kg/day for 10 days)
      is able to mitigate the reduction of synaptophysin mRNA expression induced by PCP
      in two prefrontal cortical regions, the medial prefrontal cortex (mPFC) and the
      ventrolateral orbitofrontal cortex (VLO). This effect is accompanied by a
      normalization of the PCP-induced increase in Arc mRNA expression in the same
      regions. In contrast, subsequent administration of SSR180711 does not affect PCP
      induced decreases in parvalbumin mRNA in the mPFC, and glutamate decarboxylase 67
      mRNA in the mPFC or VLO. These data demonstrate that it is possible to restore
      some, but not all, of the molecular dysregulations induced by repeated PCP
      administration with an alpha7 nAChR agonist. They also suggest that the
      previously demonstrated cognitive improvement with SSR180711 subsequent to PCP
      treatment does not require normalization of parvalbumin expression, but may
      instead be related to a restoration of synaptophysin and/or Arc levels in the
      frontal cortex. These data lend support to the potential for development of
      alpha7 nAChR agonists for the treatment of cognitive deficits in schizophrenia.

PMID- 20817067
TI  - Transglutaminase 2 expression induced by lipopolysaccharide stimulation together
      with NO synthase induction in cultured astrocytes.
AB  - Activation of glia has been observed in neurodegenerative diseases such as
      Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis and brain
      ischemia. Excessive production of nitric oxide (NO), as a consequence of
      increased inducible NO synthase (iNOS) in glia, contributes to neurodegeneration.
      Transglutaminase 2 (TG2) is a cross-linking enzyme, which is activated in
      neurodegenerative diseases such as PD, AD and Huntington's diseases. However,
      mechanisms contributing to the increased TG activity in neurodegenerative
      diseases remain to be clarified. In the present study, we examined the expression
      of TG2 in cultured rat hippocampal astrocytes activated with lipopolysaccharide
      (LPS), which is generally used for a stimulant of iNOS induction. The expressions
      of TG2 mRNA and protein were increased by stimulation with LPS in a dose
      dependent manner. The LPS-induced TG2 expression was diminished by ammonium
      pyrrolidine-1-carbodithioate; an inhibitor for nuclear factor (NF)-kappaB
      activation, suggesting the factors involved. Both expressions of TG2 and iNOS
      induced by LPS stimulation were suppressed by an antioxidant, ethyl pyruvate, in
      a dose-dependent manner. Furthermore, they were also suppressed by cystamine, an
      inhibitor of TG activity. These results suggest that the level of TG2 expression
      is regulated by oxidative stress and the activity of TG itself, and that the
      induction of iNOS and NO production are closely associated with TG2 expression in
      LPS-stimulated activation of astrocytes.

PMID- 20817069
TI  - Developmental consequences and biological significance of mother-infant bonding.
AB  - Mother-infant bonding is universal to all mammalian species. Here, we review how
      mutual communication between the mother and infant leads to mother-infant bonding
      in non-primate species. In rodents, mother-infant bond formation is reinforced by
      various pup stimuli, such as tactile stimuli and ultrasonic vocalizations.
      Evidence suggests that the oxytocin neural system plays a pivotal role in each
      aspect of the mother-infant bonding, although the mechanisms underlying bond
      formation in the brain of infants has not yet been clarified. Impairment of
      mother-infant bonding strongly influences offspring sociality. We describe the
      negative effects of mother-infant bonding deprivation on the neurobehavioral
      development in rodent offspring, even if weaning occurs in the later lactating
      period. We also discuss similar effects observed in pigs and dogs, which are
      usually weaned earlier than under natural conditions. The comparative
      understanding of the developmental consequences of mother-infant bonding and the
      underlying mechanisms provide insight into the biological significance of this
      bonding in mammals, and may help us to understand psychiatric disorders related
      to child abuse or childhood neglect.

PMID- 20817070
TI  - Monolayer cultivation of osteoprogenitors shortens duration of the embryonic stem
      cell test while reliably predicting developmental osteotoxicity.
AB  - Osteotoxic compounds administered during pregnancy can initiate skeletal
      congenital anomalies in the embryo. In vitro, developmental osteotoxicity of a
      compound can be predicted with the embryonic stem cell test (EST), the only in
      vitro embryotoxicity model identified to date that entirely abrogates the use of
      animals. Although the previously identified endpoint osteocalcin mRNA expression
      robustly predicts developmental osteotoxicity, it can only be assayed after 5
      weeks of in vitro culture with existing embryoid body (EB)-based differentiation
      protocols. Therefore, the goal of this study was to characterize novel earlier
      endpoints of developmental osteotoxicity for the EST. The currently used EB-based
      differentiation protocol was modified so that a monolayer culture of pre
      differentiated cells was inoculated. The expression profile of five bone-specific
      mRNAs, including osteocalcin, over the course of 30 differentiation days
      suggested an acceleration of pre-osteoblast specification in the monolayer over
      the EB-based protocol. Similarly, calcification was already visible after 14 days
      of culture in monolayer cultures. Employing image and absorption-based techniques
      to measure the degree of mineralization in these cells after compound treatment,
      the three compounds Penicillin G, 5-fluorouracil (5-FU) and all-trans retinoic
      acid (RA) were then tested after 14 days in monolayer cultures and compared to
      embryoid body-based differentiations at day 30. By modifying the culture the
      three test substances were classified correctly into non- or strong osteotoxic.
      Moreover, we were successful in shortening the assay duration from 30 to 14 days.

PMID- 20817071
TI  - Functional analysis of six human aryl hydrocarbon receptor variants in human
      breast cancer and mouse hepatoma cell lines.
AB  - The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor
      that mediates the toxic responses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
      The identification and functional analysis of AHR single nucleotide polymorphisms
      is important in understanding the functional diversity of this receptor as it
      might give rise to individuals with differing sensitivities to TCDD. In this
      study, the functional properties of six (I277V, P517S, R554K, V570I, Q666K, and
      R554K/V570I) human AHR variants were examined in human breast cancer cells (MCF-7
      AHR100) and mouse hepatoma cells (Hepa c12) deficient in AHR. CYP1A1- or CYP1B1
      regulated reporter gene assays in AHR100 or Hepa c12 cells exposed to TCDD
      revealed no significant differences in reporter gene activity among the different
      AHR variants. In contrast to previous findings describing the AHR-R554K/V570I
      variant to be transcriptionally deficient, no differences in TCDD-dependent
      increases in CYP1A1 and CYP1B1 mRNA levels were observed between AHR and AHR
      R554K/V570I after 24h or 48h of exposure. Chromatin immunoprecipitation assays
      also revealed similar recruitment patterns of AHR and AHR-R554K/V570I to the 5'
      regulatory regions of CYP1A1 and CYP1B1. Collectively, our findings show that
      none of the AHR variants examined exhibited an altered ability to regulate CYP1A1
      or CYP1B1-driven transcription in AHR100 or Hepa c12 cell lines, and that AHR
      and AHR-R554K/V570I are functionally equivalent in the two cell lines examined.

PMID- 20817068
TI  - Elucidating biological risk factors in suicide: role of protein kinase A.
AB  - Suicide is a major public health concern. Although there have been several
      studies of suicidal behavior that focused on the roles of psychosocial and
      sociocultural factors, these factors are of too little predictive value to be
      clinically useful. Therefore, research on the biological perspective of suicide
      has gained a stronghold and appears to provide a promising approach to identify
      biological risk factors associated with suicidal behavior. Recent studies
      demonstrate that an alteration in synaptic and structural plasticity is key to
      affective illnesses and suicide. Signal transduction molecules play an important
      role in such plastic events. Protein kinase A (PKA) is a crucial enzyme in the
      adenylyl cyclase signal transduction pathway and is involved in regulating gene
      transcription, cell survival, and plasticity. In this review, we critically and
      comprehensively discuss the role of PKA in suicidal behavior. Because stress is
      an important component of suicide, we also discuss whether stress affects PKA and
      how this may be associated with suicidal behavior. In addition, we also discuss
      the functional significance of the findings regarding PKA by describing the role
      of important PKA substrates (i.e., Rap1, cyclic adenosine monophosphate response
      element binding protein, and target gene brain-derived neurotrophic factor).
      These studies suggest the interesting possibility that PKA and related signaling
      molecules may serve as important neurobiological factors in suicide and may be
      relevant in target-specific therapeutic interventions for these disorders.

PMID- 20817072
TI  - Dipeptidyl peptidase 2 apoptosis assay determines the B-cell activation stage and
      predicts prognosis in chronic lymphocytic leukemia.
AB  - OBJECTIVE: Dipeptidyl peptidase 2 (DPP2/DPP7) is a regulator of quiescence as
      inhibition of DPP2 results in apoptosis of resting, but not activated
      lymphocytes. The purpose of the present study was to investigate the prognostic
      value of DPP2 inhibition and the role of DPP2 in cell cycle in chronic
      lymphocytic leukemia (CLL). MATERIALS AND METHODS: We screened 152 peripheral
      blood samples from patients with CLL in an apoptosis assay with AX8819, a DPP2
      specific inhibitor. The apoptotic response was correlated with B-cell receptor
      signaling and cell cycle and molecular prognostic factors. RESULTS: We
      categorized CLL into two prognostic subgroups. Inhibition of DPP2 induced
      apoptosis in 60% of CLL, while 40% were resistant to apoptosis. Resistance to
      apoptosis correlated with unmutated IgV(H) and increased ZAP-70 expression and
      was associated with unfavorable clinical outcomes. Sensitive CLL B cells
      expressed high p27, low c-Myc protein levels and decreased Syk phosphorylation,
      indicative of a resting phenotype. DPP2 inhibition in those cells resulted in
      apoptosis accompanied by enhanced phosphorylation of Syk, degradation of p27 and
      p130, and upregulation of c-Myc, indicative of activation and inappropriate cell
      cycle entry. Resistant CLL demonstrated baseline low p27 and high c-Myc protein
      levels and increased pSyk, indicative of an activated phenotype. Inhibition of
      heat shock protein 90 in this subset of CLL partially reversed apoptosis
      resistance. CONCLUSIONS: The DPP2 apoptosis assay provides a reliable prognostic
      factor in CLL. CLL B cells sensitive to DPP2 inhibition are in true G(0), while
      resistant CLL B-cells are partially activated. DPP2 inhibition alone or with
      concomitant inhibition of heat shock protein 90 warrants investigation as a
      therapeutic modality in CLL.

PMID- 20817073
TI  - HIV-1 infection inhibits cytokine production in human thymic macrophages.
AB  - OBJECTIVE: The thymus serves as a critical site of T-lymphocyte ontogeny and
      selection. Thymic infection by HIV-1 is known to disrupt thymocyte maturation by
      both direct and indirect means; however, the mechanism behind these effects
      remains poorly defined. Macrophages represent one of the most important
      peripheral targets of HIV-1 infection, are resident in the thymic stroma, and
      play a central role in thymocyte maturation. MATERIALS AND METHODS: Studies
      presented here define three primary features and outcomes of thymic macrophages
      (TM) and HIV-1 infection: (1) The distinctive TM phenotype (surface markers and
      cytokine production measured by immunofluorescence, fluorescence-activated cell
      sorting, and reverse transcriptase polymerase chain reaction) relative to
      macrophages from other sources (blood [monocyte-derived macrophages] and bone
      marrow); (2) infection of TM by different HIV-1 subtypes (X4, R5, and X4/R5)
      measured by enzyme-linked immunosorbent assay and polymerase chain reaction; and
      (3) consequences of HIV-1 infection on cytokine production by TM measured by
      reverse transcriptase polymerase chain reaction. RESULTS: The results demonstrate
      that TM display a distinctive phenotype of HIV-1 receptors (CD4(lo), CXCR4(lo),
      CCR5(med), CCR3(hi)), chemokine production (macrophage inflammatory protein
      1alpha(+); regulated on activation, normal T expressed and secreted(+);
      macrophage inflammatory protein-1b(-); stromal cell-derived factor -1(-)); and
      cytokine production (tumor necrosis factor-alpha(+), interleukin-8(+), macrophage
      colony-stimulating factor(+), interleukin-6(-)) relative to either monocyte
      derived macrophages or bone marrow. TM were infected in vitro with R5 and X4/R5
      tropic HIV-1 subtypes, and developed syncytia formation during long-term X4/R5
      culture. In contrast, TM supported only transient replication of X4-tropic HIV-1.
      Lastly, infection of TM with HIV-1 abolished the production of all cytokines
      tested in long-term in vitro cultures. CONCLUSIONS: Taken together, these results
      indicate that TM are a potential direct target of in situ HIV-1 infection, and
      that this infection may result in the disruption of macrophage functions that
      govern normal thymocyte maturation.

PMID- 20817074
TI  - Panic disorder and serotonergic genes (SLC6A4, HTR1A and HTR2A): Association and
      interaction with childhood trauma and parenting.
AB  - OBJECTIVE: The aim of this study is to evaluate the association between HTR1A,
      HTR2A and the 5-HTTLPR in panic disorder (PD) patients and controls. In addition,
      this study also aims to evaluate the interaction between these genes and two
      environmental factors previously associated with PD: childhood trauma and
      parental bonding. METHODS: This is a case-control candidate gene association
      study (107 PD patients and 125 controls). Genes were analyzed using a gene-based
      test in PLINK followed by single marker association tests and haplotype test only
      for genes that reached experiment-wide significance in the gene-based test in
      order to minimize multiple testing. Logistic regression was used to test the
      relationships between genotype in the additive model, trauma, optimal paternal
      parenting and optimal maternal parenting and their interactions. RESULTS: Only
      HTR1A was associated with PD in gene-based test after correction for multiple
      tests (p(corrected)=0.027) and one HTR1A haplotype comprising four SNPs was
      associated with PD (p(corrected)=0.032). In the interaction analysis, no
      significant gene-environment interaction was found with the genes evaluated.
      CONCLUSION: This study reinforces the association between HTR1A and PD. No major
      evidence of gene-environment interaction in PD with parenting or trauma was
      found. Further studies are necessary in order to confirm these findings.

PMID- 20817075
TI  - Isoform-specific and pan-channel partners regulate trafficking and plasma
      membrane stability; and alter sodium channel gating properties.
AB  - Voltage-gated sodium channels are cell membrane glycoproteins responsible for
      action potential generation and propagation in excitable cells. These large
      polypeptides which are comprised of 24 transmembrane segments organized into four
      domains require cellular factors to regulate channel maturation and sorting to
      different cellular compartments, anchoring the channels at plasma membrane, and
      modulating gating properties of these channels as effector molecules in the
      signal transduction pathway. Mutations of sodium channels or their cytosolic
      partners produce similar pathologies, providing a compelling evidence for the
      biological significance of channel complexes that form during channel biogenesis
      and following sorting to different cellular compartments and anchoring at plasma
      membrane. Genetic, biochemical and bioinformatic approaches have been utilized to
      identify sodium channel partners. Here we review the important functional role of
      pan-sodium channel and isoform-specific partners in regulating sodium current
      density and gating properties.

PMID- 20817077
TI  - Voltage-gated sodium channel organization in neurons: protein interactions and
      trafficking pathways.
AB  - In neurons, voltage-gated sodium (Nav) channels underlie the generation and
      propagation of the action potential. The proper targeting and concentration of
      Nav channels at the axon initial segment (AIS) and at the nodes of Ranvier are
      therefore vital for neuronal function. In AIS and nodes, Nav channels are part of
      specific supra-molecular complexes that include accessory proteins, adhesion
      proteins and cytoskeletal adaptors. Multiple approaches, from biochemical
      characterization of protein-protein interactions to functional studies using
      mutant mice, have addressed the mechanisms of Nav channel targeting to AIS and
      nodes. This review summarizes our current knowledge of both the intrinsic
      determinants and the role of partner proteins in Nav targeting. A few fundamental
      trafficking mechanisms, such as selective endocytosis and diffusion/retention,
      have been characterized. However, a lot of exciting questions are still open,
      such as the mechanism of differentiated Nav subtype localization and targeting,
      and the possible interplay between electrogenesis properties and Nav
      concentration at the AIS and the nodes.

PMID- 20817076
TI  - Alzheimer's secretases regulate voltage-gated sodium channels.
AB  - BACE1 and presenilin (PS)/gamma-secretase are primary proteolytic enzymes
      responsible for the generation of pathogenic amyloid beta-peptides (Abeta) in
      Alzheimer's disease. We and others have found that beta-subunits of the voltage
      gated sodium channel (Na(v)betas) also undergo sequential proteolytic cleavages
      mediated by BACE1 and PS/gamma-secretase. In a follow-up study, we reported that
      elevated BACE1 activity regulates total and surface expression of voltage-gated
      sodium channels (Na(v)1 channels) and thereby modulates sodium currents in
      neuronal cells and mouse brains. In this review, we focus on the molecular
      mechanism of how BACE1 and PS/gamma-secretase regulate Na(v)1 channels in
      neuronal cells. We will also discuss potential physiological and pathological
      roles of BACE1- and PS/gamma-secretase-mediated processing of Na(v)betas in
      relation to Na(v)1 channel function.

PMID- 20817078
TI  - Skin sensory information from the dorsum of the foot and ankle is necessary for
      kinesthesia at the ankle joint.
AB  - Previous research has shown that skin is capable of providing kinesthetic cues at
      particular joints but we are unsure how these cues are used by the central
      nervous system. The current study attempted to identify the role of skin on the
      dorsum of the ankle during a joint matching task. A 30cm patch of skin was
      anesthetized and matching accuracy in a passive joint matching task was compared
      before and after skin anesthetization. Goniometers were used to measure ankle
      angular displacement. Four target angles were used in the matching task, 7
      degrees  of dorsiflexion, 7 degrees , 14 degrees  and 21 degrees  of
      plantarflexion. We hypothesized that, based on the location of skin anesthetized,
      only the plantarflexion matching tasks would be affected. Absolute error
      (accuracy) increased significantly for all angles when the skin was anesthetized.
      Directional error indicated that overall subjects tended to undershoot the target
      angles, significantly more so for 21 degrees  of plantarflexion when the skin was
      anesthetized. Following anesthetization, variable error (measure of task
      difficulty) increased significantly at 7 degrees  of dorsiflexion and 21 degrees 
      of plantarflexion. These results indicate that the subjects were less accurate
      and more variable when skin sensation was reduced suggesting that skin
      information plays an important role in kinesthesia at the ankle.

PMID- 20817079
TI  - Cocaine selectively increases proliferation in the adult murine hippocampus.
AB  - Cocaine abuse continues to be a significant problem in the USA and elsewhere.
      Cocaine is an indirect agonist for dopamine, norepinephrine and serotonin with
      numerous potential downstream effects, including processes and signals associated
      with adult neurogenesis. Since drug addiction is associated with brain
      plasticity, we hypothesized that cocaine exposure would alter cellular
      proliferation in two adult neurogenic regions (the subventricular and subgranular
      zones). We used bromodeoxyuridine (BrdU) to track newly generated cells in the
      brains of adult mice after chronic cocaine or saline exposures. No differences
      were found in the number or migration patterns of BrdU-labeled cells in the
      forebrain neurogenic areas. However, cocaine produced a significant increase in
      the number of hippocampal BrdU-labeled cells.

PMID- 20817080
TI  - Nanogel particulates located within diffusion cell receptor phases following
      topical application demonstrates uptake into and migration across skin.
AB  - Despite growing evidence in support of nanogels as carriers in topical drug
      delivery, no empirical evidence has been forthcoming regarding a mechanism.
      Poly(N-isopropylacrylamide-copolymerized-acrylic acid) referred to as poly(NIPAM
      co-AAc) and poly(N-isopropylacrylamide) known as (polyNIPAM) nanogels were
      synthesized by a surfactant-free emulsion polymerisation method and applied to
      porcine ear skin mounted in Franz diffusion cells. After 24h the receptor phases
      were retrieved and scrutinized by transmission electron microscopy (TEM). The
      skin membranes were also recovered and re-used to determine the permeation of a
      model permeant, methotrexate (MTX). TEM images confirmed the presence of
      nanoparticulates in the receptor phases, and the relative quantities varied on
      the nature of the nanogel. Comparative MTX skin permeation data demonstrated the
      integrity of the membranes, and that delivery of nanogel or MTX was not due to
      defects in the membranes. In summary, the first direct evidence is presented
      demonstrating that nanogels are taken up by and migrate across the skin.

PMID- 20817081
TI  - Recognition of temporally interrupted and spectrally degraded sentences with
      additional unprocessed low-frequency speech.
AB  - Recognition of periodically interrupted sentences (with an interruption rate of
      1.5 Hz, 50% duty cycle) was investigated under conditions of spectral
      degradation, implemented with a noiseband vocoder, with and without additional
      unprocessed low-pass filtered speech (cutoff frequency 500 Hz). Intelligibility
      of interrupted speech decreased with increasing spectral degradation. For all
      spectral degradation conditions, however, adding the unprocessed low-pass
      filtered speech enhanced the intelligibility. The improvement at 4 and 8 channels
      was higher than the improvement at 16 and 32 channels: 19% and 8%, on average,
      respectively. The Articulation Index predicted an improvement of 0.09, in a scale
      from 0 to 1. Thus, the improvement at poorest spectral degradation conditions was
      larger than what would be expected from additional speech information. Therefore,
      the results implied that the fine temporal cues from the unprocessed low
      frequency speech, such as the additional voice pitch cues, helped perceptual
      integration of temporally interrupted and spectrally degraded speech, especially
      when the spectral degradations were severe. Considering the vocoder processing as
      a cochlear implant simulation, where implant users' performance is closest to 4
      and 8-channel vocoder performance, the results support additional benefit of low
      frequency acoustic input in combined electric-acoustic stimulation for perception
      of temporally degraded speech.

PMID- 20817082
TI  - Effects of Scutellariae radix and Aloe vera gel extracts on immunoglobulin E and
      cytokine levels in atopic dermatitis NC/Nga mice.
AB  - AIM OF THE STUDY: The present study aimed to investigate the effects of
      Scutellariae radix (SR) and Aloe vera gel (AV), alone or in combination, on
      levels of immunoglobulin E (IgE) and inflammatory cytokines in spontaneous atopic
      dermatitis(AD)-like skin lesions. MATERIALS AND METHODS: After spontaneous AD
      like skin lesion was developed by adaptation to conventional conditions, mice
      were randomly assigned to control, SR (50 mg/kg, p.o.), AV (0.8 mg/kg, p.o.) and
      SRAV (50 mg of SR and 0.8 mg of AV/kg, p.o.) groups, and were treated for 6
      weeks. RESULTS: SR and SRAV suppressed IL-5 levels compared with control, but had
      no effects on IgE levels (P<0.05). AV increased IgE levels, but decreased both IL
      5 and IL-10 compared with control (P<0.05). CONCLUSION: These results suggest
      that SR and AV modulate immunological responses in AD, mainly through influencing
      IL-5 or IL-10 levels.

PMID- 20817083
TI  - Effects of lignans extracted from Eucommia ulmoides and aldose reductase
      inhibitor epalrestat on hypertensive vascular remodeling.
AB  - AIM OF THE STUDY: To investigate the effects of lignans extracted from Eucommia
      ulmoides and epalrestat on vascular remodeling in spontaneously hypertensive
      rats. MATERIALS AND METHODS: Ten-week-old male spontaneously hypertensive rats
      were randomly divided into 3 groups (12 rats each group), and treated orally with
      100 mg/kg/d of captopril (an angiotensin-converting enzyme inhibitor), 100
      mg/kg/d of epalrestat (an aldose reductase inhibitor) and 300 mg/kg/d of lignans
      by gavage daily for 16 weeks, respectively. Sex-, age-, and number-matched
      spontaneously hypertensive rats and normotensive Wistar Kyoto rats, were treated
      with distilled water (vehicle) as controls. The rats were weighed weekly. Mean
      arterial blood pressure and heart rate were measured periodically by non-invasive
      blood pressure monitoring. They were sacrificed at the end of experiment (26-week
      old). Superior mesenteric artery and aorta were isolated for determination of
      histomorphometry and the expression of aldose reductase by immunohistochemistry.
      RESULTS: Captopril and lignans, but not epalrestat, decreased mean arterial blood
      pressure in spontaneously hypertensive rats. Vascular remodeling was improved in
      all three treated groups by histomorphometry. CONCLUSIONS: Both lignans and
      epalrestat reversed hypertensive vascular remodeling. Aldose reductase played a
      vital role in the pathologic process of hypertensive vascular remodeling rather
      than elevation of blood pressure. These data suggested that aldose reductase
      could be a new therapeutic target for the treatment of cardiovascular diseases.

PMID- 20817084
TI  - The anti-diarrhoeal properties of Breonadia salicina, Syzygium cordatum and
      Ozoroa sphaerocarpa when used in combination in Swazi traditional medicine.
AB  - AIM OF THE STUDY: The aim of the study was to determine in vitro activity of the
      bark of Ozoroa sphaerocarpa R. Fern & A. Fern (Anacardiaceae), Breonadia salicina
      (Vahl) Hepper & J.I.R. Wood (Rubiaceae) and Syzygium cordatum Hochst ex C Krauss
      (Myrtaceae) against a diarrhoea-causing pathogen, Escherichia coli; as well as
      the pharmacological interactions present in their combination. MATERIALS AND
      METHODS: In consultation with traditional healers, the plants were collected from
      the wild, dried and extracted with dichloromethane:methanol (1:1). Thereafter,
      antimicrobial activity of the individual plants and their different combinations
      was tested using a common diarrhoea pathogen, Escherichia coli by employing the
      minimum inhibitory concentration assay. RESULTS: Ozoroa sphaerocarpa was the most
      potent inhibitor of antimicrobial growth (MIC value of 1.2 mg/ml), followed by
      Syzygium cordatum (MIC value of 1.44 mgl/ml) and lastly Breonadia salicina (MIC
      value of 10.89 mg/ml). The combination between Syzygium cordatum and Ozoroa
      sphaerocarpa gave the strongest synergistic interaction (MIC value of 0.33
      mg/ml); whilst that between Syzygium cordatum and Breonadia salicina was mildly
      synergistic (MIC value of 1.00 mg/ml). The triple combination (1:1:1) was also
      very effective in inhibiting microbial growth (MIC value of 0.44 mg/ml). The
      combined effect of these plants on toxicity was predominantly synergistic except
      for the combination of Ozoroa sphaerocarpa and Syzygium cordatum which was
      predominantly antagonistic (SigmaFIC value of 1.48 +/- 0.25). The triple
      combination had a favourable toxicity profile with an IC(50) value of 155.76 +/-
      11.86 MUg/ml. CONCLUSION: This study supports the rationale by traditional
      healers to use the bark of Syzygium cordatum, Breonadia salicina and Ozoroa
      sphaerocarpa in combination for the treatment of diarrhoea.

PMID- 20817085
TI  - Ethno-veterinary uses and informants consensus factor of medicinal plants of
      Sariska region, Rajasthan, India.
AB  - AIM OF STUDY: The study was conducted in Sariska region of Rajasthan, India to
      identify the important species used for ethno-veterinary medicine; finding out
      methods for various ethno-veterinary medicine preparations, and calculate the
      informant consensus factor (ICF) in relation to medicinal plant use. MATERIALS
      AND METHODS: An ethno-veterinary survey was carried out in the Sariska region of
      Rajasthan, India. A total of 490 informants (287 men, 203 women) belonging mainly
      to families which had strong links with animal keeping activities of the area
      were interviewed using 'specimen display' method and forest walk method. RESULTS:
      The highest ICF (0.61) was scored for the digestive problems including ailments
      stomachache, indigestion, liver expansion, diarrhea, intestinal worms, and
      stomach disorder. Citrullus colocynthis is used for fever and general sickness,
      with a highest use value (UV) of 0.62. While Pedalium murex, and Ziziphus
      nummularia used for diarrhea (UV=0.57) and Azadirachta indica, used as
      antiseptic, in foot and mouth disease and prevention from diseases were reported
      with a UV 0.51. CONCLUSIONS: The documentation of this inherited rich traditional
      ethno-medicinal knowledge has provided novel information and this will not only
      provide recognition of this undocumented knowledge but will also help in
      conservation of such rare, gradually vanishing important ethno-veterinary
      species. It will also provide new pharmacological dimensions for better health
      care of the human being regarding many ailments.

PMID- 20817086
TI  - Melatonin improves inflammation processes in liver of senescence-accelerated
      prone male mice (SAMP8).
AB  - Aging is associated with an increase in oxidative stress and inflammation. The
      aim of this study was to investigate the effect of aging on various physiological
      parameters related to inflammation in livers obtained from two types of male mice
      models: Senescence-accelerated prone (SAMP8) and senescence-accelerated-resistant
      (SAMR1) mice, and to study the influence of the administration of melatonin
      (1mg/kg/day) for one month on old SAMP8 mice on these parameters. The parameters
      studied have been the mRNA expression of TNF-alpha, iNOS, IL-1beta, HO-1, HO-2,
      MCP1, NFkB1, NFkB2, NFkB protein or NKAP and IL-10. All have been measured by
      real-time reverse transcription polymerase chain reaction RT-PCR. Furthermore we
      analyzed the protein expression of TNF-alpha, iNOS, IL-1beta, HO-1, HO-2, and IL
      10 by Western-blot. Aging increased oxidative stress and inflammation especially
      in the liver of SAMP8 mice. Treatment with melatonin decreased the mRNA
      expression of TNF-alpha, IL-1beta, HO (HO-1 and HO-2), iNOS, MCP1, NFkappaB1,
      NFkappaB2 and NKAP in old male mice. The protein expression of TNF-alpha, IL
      1beta was also decreased and IL-10 increased with melatonin treatment and no
      significant differences were observed in the rest of parameters analyzed. The
      present study showed that aging was related to inflammation in livers obtained
      from old male senescence prone mice (SAMP8) and old male senescence resistant
      mice (SAMR1) being the alterations more evident in the former. Exogenous
      administration of melatonin was able to reduce inflammation.

PMID- 20817087
TI  - Olive oil improved the impairment of in vitro insulin-stimulated glucose uptake
      by diaphragm in ovariectomized female Wistar rats.
AB  - This work was carried out to examine the impact of ovariectomy in female Wistar
      rats on in vitro basal and insulin-stimulated glucose uptake by diaphragm, and
      the possible beneficial effects of olive oil supplementation in these rats.
      METHODS: we studied 21 female Wistar rats aged 12-14 months, divided into three
      groups: sham-operated control (SHAM), ovariectomized (OVX), and ovariectomized
      rats supplemented with extra-virgin olive oil (Olive-OVX) orally for 12 weeks; 4
      weeks before ovariectomy and 8 weeks after. At the end of the experiment, blood
      samples were collected for lipid profile assays. Malondialdehyde (MDA) in soleus
      muscles was assayed. The diaphragms were collected for determination of glucose
      uptake by the muscles. Soleus muscles and pancreas were processed for
      histological examination. RESULTS: ovariectomy impaired insulin-stimulated
      glucose uptake by diaphragm of female rats, induced abnormalities of lipid
      metabolism, and increased the oxidative stress marker, MDA level in soleus
      muscles. Olive oil supplementation to ovariectomized rats resulted in an
      enhancement of insulin-stimulated glucose uptake by diaphragm and a better lipid
      profile, as well as a decrease in the MDA level in soleus muscles. Histological
      study in OVX rats revealed a decrease in the size and number of islets of
      Langerhans in the pancreatic tissue, and decreases in both glycogen content, and
      in mitochondrial density in the soleus muscles. In Olive-OVX rats the size of
      islets of Langerhans was normal, and muscle glycogen, and muscle mitochondrial
      density were increased as compared to OVX rats. CONCLUSION: ovariectomy impaired
      in vitro insulin-stimulated glucose uptake by diaphragm. The improvement of this
      impairment by olive oil supplementation could be attributed to its antioxidant
      properties, its high content of monounsaturated fatty acids, as well as, its
      enhancement effect on mitochondrial density in skeletal muscles.

PMID- 20817088
TI  - Tethering antimicrobial peptides: current status and potential challenges.
AB  - Antimicrobial peptides (AMPs) are next generation antibiotics which will make
      excellent coating agents for a myriad of devices because they are far less
      susceptible to the development of pathogen resistance compared to conventional
      antibiotics, exhibit rapid and broad-spectrum killing profiles, and are effective
      at low concentrations. These advantages, however, are compromised upon AMP
      tethering to solid supports. The effects of peptide-tethering strategies in
      governing AMP orientation, surface density, flexibility, and activity are
      reviewed. Understanding AMP structure-function relationship in the tethered
      conformation will enable rational improvements of immobilisation parameters.
      Foreseeable challenges in the development of AMP-coated devices such as microbial
      accumulation on implant surface and the lack of direct biomolecular structure and
      orientation data of peptides on surfaces are also discussed, and solutions to
      address these roadblocks are also proposed.

PMID- 20817089
TI  - Hemolytic activity in Flavobacterium psychrophilum is a contact-dependent, two
      step mechanism and differently expressed in smooth and rough phenotypes.
AB  - The hemolytic activity of cells of smooth and rough phenotypic variants of the
      Gram-negative fish pathogen Flavobacterium psychrophilum was investigated in two
      different assays, a microplate and an agarose hemolysis assay, using rainbow
      trout erythrocytes. The smooth cells showed a high and the rough cells a
      negligible, concentration dependent, hemolytic activity in the microplate assay.
      Both smooth and rough cells showed a rather weak hemolytic activity, with two
      distinct hemolytic patterns, in the agarose assay. The hemolytic activity of the
      cells was not regulated by iron availability and cell-free extracellular products
      did not show any hemolytic activity. The smooth cells, in contrast to the rough
      cells, showed a high ability to agglutinate erythrocytes and both
      hemagglutination and hemolytic activity was impaired by treatment of the cells
      with sialic acid. The hemolytic activity was furthermore reduced after
      proteolytic and heat treatment of the cells. The results from the present study
      suggest that the hemolytic activity in F. psychrophilum is highly expressed in
      the smooth phenotype, and that it is a contact-dependent and two-step mechanism
      that is initiated by the binding of the bacterial cells to the erythrocytes
      through sialic acid-binding lectins and then executed by thermolabile
      proteinaceous hemolysins.

PMID- 20817090
TI  - Androgen activation of the folate receptor alpha gene through partial tethering
      of the androgen receptor by C/EBPalpha.
AB  - The folate receptor alpha (FRalpha) is critical for normal embryonic and fetal
      development. The receptor has a relatively narrow tissue specificity which
      includes the visceral endoderm and the placenta and mediates delivery of folate,
      inadequacy of which results in termination of pregnancy or developmental defects.
      We have previously reported that the FRalpha gene is negatively and directly
      regulated by estrogen and positively but indirectly by progesterone and
      glucocorticoid. To further investigate hormonal control of this gene and in view
      of the growing evidence for the importance of the androgen receptor (AR) in
      endometrial and placental functions, we examined the response of the FRalpha gene
      to androgen. Here we demonstrate that the FRalpha gene is directly activated by
      androgen. The P4 promoter of the FRalpha gene is the target of hormone-dependent
      activation by the androgen receptor (AR) in a manner that is co-activator
      dependent. The site of functional association of AR in the FRalpha gene maps to a
      35bp region occurring ~1500bp upstream of the target promoter. The functional
      elements within this region are an androgen response element (ARE) half-site and
      a non-canonical C/EBP element that cooperate to recruit AR in a manner that is
      dependent on the DNA-bound C/EBPalpha. Since the placenta is rich in C/EBPalpha,
      the findings underscore the multiplicity of mechanisms by which the FRalpha gene
      is under the exquisite control of steroid hormones.

PMID- 20817091
TI  - Retina-specific activation of a sustained hypoxia-like response leads to severe
      retinal degeneration and loss of vision.
AB  - Loss of vision and blindness in human patients is often caused by the
      degeneration of neuronal cells in the retina. In mouse models, photoreceptors can
      be protected from death by hypoxic preconditioning. Preconditioning in low oxygen
      stabilizes and activates hypoxia inducible transcription factors (HIFs), which
      play a major role in the hypoxic response of tissues including the retina. We
      show that a tissue-specific knockdown of von Hippel-Lindau protein (VHL)
      activated HIF transcription factors in normoxic conditions in the retina.
      Sustained activation of HIF1 and HIF2 was accompanied by persisting embryonic
      vasculatures in the posterior eye and the iris. Embryonic vessels persisted into
      adulthood and led to a severely abnormal mature vessel system with vessels
      penetrating the photoreceptor layer in adult mice. The sustained hypoxia-like
      response also activated the leukemia inhibitory factor (LIF)-controlled
      endogenous molecular cell survival pathway. However, this was not sufficient to
      protect the retina against massive cell death in all retinal layers of adult
      mice. Caspases 1, 3 and 8 were upregulated during the degeneration as were
      several VHL target genes connected to the extracellular matrix. Misregulation of
      these genes may influence retinal structure and may therefore facilitate growth
      of vessels into the photoreceptor layer. Thus, an early and sustained activation
      of a hypoxia-like response in retinal cells leads to abnormal vasculature and
      severe retinal degeneration in the adult mouse retina.

PMID- 20817093
TI  - Functional rescue of excitatory synaptic transmission in the developing
      hippocampus in Fmr1-KO mouse.
AB  - Pharmaceutical treatments are being developed to correct specific behavioural and
      morphological aspects of neurodevelopmental disorders such as mental retardation.
      Fragile X syndrome is an X-linked mental retardation with abnormal dendritic
      protrusions from neurons in the brain. Increased signalling via excitatory
      metabotropic glutamate receptor (mGluR) pathways is hypothesised to contribute to
      this disorder. Targeting these receptors has shown improvements in both behaviour
      and morphology with the Fmr1-KO mouse model for the syndrome. It is not known
      whether similar changes occur in excitatory synaptic activity following treatment
      with mGluR antagonists. We tested the effects of prolonged mGluR blockade on
      excitatory synaptic activity at three developmental time points in hippocampal
      slices. We observed a rescue effect of the antagonist MPEP upon spontaneous EPSC
      amplitude and charge at 2 weeks but not 1 week or 8-10 weeks of development.
      These data support the role of mGluR antagonist treatment for functional synaptic
      correction at an early developmental stage in a model for fragile X syndrome.

PMID- 20817094
TI  - Mitochondrial membrane potential decrease caused by loss of PINK1 is not due to
      proton leak, but to respiratory chain defects.
AB  - Mutations in PTEN-induced putative kinase 1 (PINK1) cause a recessive form of
      Parkinson's disease (PD). PINK1 is associated with mitochondrial quality control
      and its partial knock-down induces mitochondrial dysfunction including decreased
      membrane potential and increased vulnerability against mitochondrial toxins, but
      the exact function of PINK1 in mitochondria has not been investigated using cells
      with null expression of PINK1. Here, we show that loss of PINK1 caused
      mitochondrial dysfunction. In PINK1-deficient (PINK1(-/-)) mouse embryonic
      fibroblasts (MEFs), mitochondrial membrane potential and cellular ATP levels were
      decreased compared with those in littermate wild-type MEFs. However,
      mitochondrial proton leak, which reduces membrane potential in the absence of ATP
      synthesis, was not altered by loss of PINK1. Instead, activity of the respiratory
      chain, which produces the membrane potential by oxidizing substrates using
      oxygen, declined. H(2)O(2) production rate by PINK1(-/-) mitochondria was lower
      than PINK1(+/+) mitochondria as a consequence of decreased oxygen consumption
      rate, while the proportion (H(2)O(2) production rate per oxygen consumption rate)
      was higher. These results suggest that mitochondrial dysfunctions in PD
      pathogenesis are caused not by proton leak, but by respiratory chain defects.

PMID- 20817092
TI  - Neurophysiology of dystonia: The role of inhibition.
AB  - The pathophysiology of dystonia has been best studied in patients with focal hand
      dystonia. A loss of inhibitory function has been demonstrated at spinal,
      brainstem and cortical levels. Many cortical circuits seem to be involved. One
      consequence of the loss of inhibition is a failure of surround inhibition, and
      this appears to directly lead to overflow and unwanted muscle spasms. There are
      mild sensory abnormalities and deficits in sensorimotor integration; these also
      might be explained by a loss of inhibition. Increasing inhibition may be
      therapeutic. A possible hypothesis is that there is a genetic loss of inhibitory
      interneurons in dystonia and that this deficit is a substrate on which other
      factors can act to produce dystonia. This article is part of a Special Issue
      entitled "Advances in dystonia".

PMID- 20817095
TI  - CD38 as a molecular compass guiding topographical decisions of chronic
      lymphocytic leukemia cells.
AB  - CLL is characterized by a dynamic balance between cells proliferating in the
      lymphoid organs and circulating cells resisting programmed cell death. Regulating
      this equilibrium entails complex interactions between tumor and host, modulated
      by a set of surface molecules expressed by the CLL cell according to
      environmental conditions. The result is a constantly shifting pattern of
      resistance, apoptosis and proliferation. The CD38 surface molecule is an
      independent negative prognostic factor expressed by approximately one-third of
      CLL patients. Our view is that CD38 is crucial to tumor-host communication and
      that its signals are detrimental to clinical outcome. CD38(+) CLL cells can
      proliferate in vitro in the presence of anti-CD38 mAbs and IL-2 and are more
      sensitive to the effects of the CXCL12 chemokine. Blockage of CD38 signals
      impairs CLL cell movement from blood to lymphoid organs, as confirmed using
      animal models. One model to be explored considers CD38 a key component of the CLL
      invadosome, a still hypothetical membrane domain containing adhesion molecules,
      chemokine receptors and matrix metalloproteases. Some components of the
      invadosome are genetically polymorphic, explaining heterogeneity in functional
      response. The CD38 gene shows genetic differences in the promoter region, some of
      which represent an independent risk for Richter transformation. In addition to
      driving the clinical outcome of the disease, CD38 is thus an excellent candidate
      therapeutic target for a significant subset of CLL patients.

PMID- 20817096
TI  - Which way to go? Cytoskeletal organization and polarized transport in neurons.
AB  - To establish and maintain their polarized morphology, neurons employ active
      transport driven by cytoskeletal motor proteins to sort cargo between axons and
      dendrites. These motors can move in a specific direction over either microtubules
      (kinesins, dynein) or actin filaments (myosins). The basic traffic rules
      governing polarized transport on the neuronal cytoskeleton have long remained
      unclear, but recent work has revealed several fundamental sorting principles
      based on differences in the cytoskeletal organization in axons versus dendrites.
      We will highlight the basic characteristics of the neuronal cytoskeleton and
      review existing evidence for microtubule and actin based traffic rules in
      polarized neuronal transport. We will propose a model in which polarized sorting
      of cargo is established by recruiting or activating the proper subset of motor
      proteins, which are subsequently guided to specific directions by the polarized
      organization of the neuronal cytoskeleton.

PMID- 20817097
TI  - A three-step model for the synaptic recruitment of AMPA receptors.
AB  - The amount of AMPARs at synapses is not a fixed number but varies according to
      different factors including synaptic development, activity and disease. Because
      the number of AMPARs sets the strength of synaptic transmission, their
      trafficking is subject to fine and tight regulation. In this review, we will
      describe the different steps taken by AMPARs in order to reach the synapse. We
      propose a three-step mechanism involving exocytosis at extra/perisynaptic sites,
      lateral diffusion to synapses and a subsequent rate-limiting diffusional trapping
      step. We will describe how the different trafficking steps are regulated during
      synaptic plasticity or altered during neurodegenerative diseases such as
      Alzheimer's.

PMID- 20817098
TI  - A novel protein refolding system using lauroyl-l-glutamate as a solubilizing
      detergent and arginine as a folding assisting agent.
AB  - More than 50 detergents, including acylated amino acid derivatives, were screened
      for their ability to solubilize and refold recombinant proteins expressed as
      inclusion bodies. Two model proteins, human interleukin-6 and microbial
      transglutaminase, were solubilized by these detergents and the solubilized
      proteins were rapidly diluted for testing their solubilization and refolding
      effectiveness. Long chain-acylated amino acid derivatives having dicarboxylic
      acid moieties were found to be superior to others under the conditions tested. In
      particular, lauroyl-l-glutamate (C12-l-Glu) showed the highest recovery of the
      native proteins. The effectiveness of dilution refolding was greatly improved by
      adding aggregation suppressive arginine into the refolding solvents. To gain
      understanding how this detergent works, interactions between detergents and
      proteins were examined using spectroscopic and native gel electrophoretic
      analyses, showing ideal properties for C12-l-Glu as a solubilzing agent, i.e.
      highly reversible nature of the detergent binding to the model globular proteins
      and of the conformational changes. These properties most likely have contributed
      to the effective protein solubilzation and refolding of inclusion bodies using
      C12-l-Glu and arginine.

PMID- 20817099
TI  - A new tagged-TEV protease: construction, optimisation of production, purification
      and test activity.
AB  - The Tobacco Etch Virus (TEV) protease is frequently used in the cleavage of
      recombinant fusion proteins because of its efficiency and high specificity. In
      this work, we present a new recombinant form of TEV termed Streptag II-TEV for
      high-level production and purification of TEV protease from Escherichia coli and
      compare it to the hexahistidine (6xHis) tagged version of TEV. The effects of
      varying the host strain, the bacterial induction temperature (25, 30 and 37
      degrees C) and the IPTG inducer concentration on production and solubility of the
      two recombinant TEV proteases have been examined. Optimal Streptag II-TEV protein
      expression were obtained in the E. coli KRX strain under an induction temperature
      of 25 degrees C in the presence of IPTG at 0.5 mM. In these conditions, soluble
      Streptag II-TEV and 6xHis-TEV proteases accounted for about 25% and 18% of total
      soluble proteins, respectively. About 70% of Streptag II-TEV and 60% of 6xHis-TEV
      were detected in the supernatant. Streptag II-TEV protease purifies to near
      homogeneity (approximately 99%) via a simple, single step Strep-Tactin
      chromatography purification protocol based on the presence of Streptag II. The
      higher production of Streptag II-TEV coupled to its purification and cleavage
      efficiencies make it an attractive alternate to 6xHis-TEV.

PMID- 20817100
TI  - An approach to automated acquisition of cryoEM images from lacey carbon grids.
AB  - An approach to automated acquisition of cryoEM image data from lacey carbon grids
      using the Leginon program is described. Automated liquid nitrogen top up of the
      specimen holder dewar was used as a step towards full automation, without
      operator intervention during the course of data collection. During cryoEM studies
      of actin labelled with myosin V, we have found it necessary to work with lacey
      grids rather than Quantifoil or C-flat grids due to interaction of myosin V with
      the support film. Lacey grids have irregular holes of variable shape and size, in
      contrast to Quantifoil or C-flat grids which have a regular array of similar
      circular holes on each grid square. Other laboratories also prefer to work with
      grids with irregular holes for a variety of reasons. Therefore, it was necessary
      to develop a different strategy from normal Leginon usage for working with lacey
      grids for targeting holes for image acquisition and suitable areas for focussing
      prior to image acquisition. This approach was implemented by using the extensible
      framework provided by Leginon and by developing a new MSI application within that
      framework which includes a new Leginon node (for a novel method for finding focus
      targets).

PMID- 20817101
TI  - Replacement of dietary fish oil by vegetable oils affects humoral immunity and
      expression of pro-inflammatory cytokines genes in gilthead sea bream Sparus
      aurata.
AB  - Commercial gilthead sea bream feeds are highly energetic, fish oil traditionally
      being the main lipid source. But the decreased fish oil production together with
      the increased prices of this oil encourages its substitution by vegetable oils,
      imposing new nutritional habits to aquaculture species. Partial replacement of
      fish oil by vegetable oils in diets for marine species allows good feed
      utilization and growth but may affect fish health, since imbalances in dietary
      fatty acids may alter fish immunological status. The effect of dietary oils on
      different aspects of fish immune system has been reported for some species, but
      very little is known about the effect of dietary oils on immune-related genes
      expression in fish. Thus, the objective of this study was to elucidate the role
      of dietary oils on the expression of two pro-inflammatory cytokines, Tumor
      Necrosis Factor-alpha (TNF-alpha) and Interleukine 1beta (IL-1beta) on intestine
      and head kidney after exposure to the bacterial pathogen Photobacterium damselae
      sp. piscicida. For that purpose, 5 iso-nitrogenous and iso-lipidic diets (45%
      crude protein, 22% crude lipid content) were formulated. Anchovy oil was the only
      lipid source used in the control diet (FO), but in the other diets, fish oil was
      totally (100%) or partially (70%) substituted by linseed (rich in n-3 fatty
      acids) or soybean (rich in n-6 fatty acids) (100L, 100S, 70L, 70S). Fish were fed
      experimental diets during 80 days and after this period were exposed to an
      experimental intestinal infection with the pathogen. Serum and tissue samples
      were obtained at pre-infection and after 1, 3 and 7 days of infection. RNA was
      extracted and cDNA was synthesized by reverse transcription from intestine and
      head kidney and the level expression of TNF-alpha and IL-1beta were assayed by
      using quantitative real time PCR. The expression level of genes analysed was
      represented as relative value, using the comparative Ct method (2(
      DeltaDeltaCt)). Serum anti-bacterial activity was measured as serum bactericidal
      capacity and lysozyme activity. Reduction of FO tends to reduce basal (pre
      infection) genetic expression of both cytokines. However, complete FO replacement
      caused an over expression of both pro-inflammatory cytokines, particularly after
      3 days of induced infection in fish fed soybean oil based diets. On the other
      hand, fish fed diets with low content of n-6 fatty acids showed better serum
      bactericidal capacity after infection, suggesting that the substitution of fish
      oil by vegetable oils containing high levels of n-6 fatty acids may induce
      imbalances on fish immune response, leading to a lower potential response against
      infections.

PMID- 20817102
TI  - CNS activation maps in awake rats exposed to thermal stimuli to the dorsum of the
      hindpaw.
AB  - Imaging pain pathways in rats offers a tool to investigate CNS systems in acute
      and chronic rodent models of pain, neural plasticity associated with the latter,
      and the opportunity to evaluate pharmacological effects of analgesics on these
      systems. Furthermore, the evaluation of CNS circuits (e.g., sensory, emotional,
      endogenous analgesic) offers the potential for defining the complexity of circuit
      based behaviors that are difficult to evaluate in current preclinical behavioral
      models of pain. In these studies, we performed functional MRI in trained,
      acclimated, awake rats to define neural systems activated by noxious thermal
      stimuli. Analysis revealed activation in response to a 48 degrees C stimuli in
      cortical, subcortical and brainstem areas, known to be substrates of the pain
      pathways. Our results demonstrate the ability to characterize CNS patterns of
      activation in response to pain in rodents while avoiding the potential
      complicating effects of anesthesia.

PMID- 20817103
TI  - Network modelling methods for FMRI.
AB  - There is great interest in estimating brain "networks" from FMRI data. This is
      often attempted by identifying a set of functional "nodes" (e.g., spatial ROIs or
      ICA maps) and then conducting a connectivity analysis between the nodes, based on
      the FMRI timeseries associated with the nodes. Analysis methods range from very
      simple measures that consider just two nodes at a time (e.g., correlation between
      two nodes' timeseries) to sophisticated approaches that consider all nodes
      simultaneously and estimate one global network model (e.g., Bayes net models).
      Many different methods are being used in the literature, but almost none has been
      carefully validated or compared for use on FMRI timeseries data. In this work we
      generate rich, realistic simulated FMRI data for a wide range of underlying
      networks, experimental protocols and problematic confounds in the data, in order
      to compare different connectivity estimation approaches. Our results show that in
      general correlation-based approaches can be quite successful, methods based on
      higher-order statistics are less sensitive, and lag-based approaches perform very
      poorly. More specifically: there are several methods that can give high
      sensitivity to network connection detection on good quality FMRI data, in
      particular, partial correlation, regularised inverse covariance estimation and
      several Bayes net methods; however, accurate estimation of connection
      directionality is more difficult to achieve, though Patel's tau can be reasonably
      successful. With respect to the various confounds added to the data, the most
      striking result was that the use of functionally inaccurate ROIs (when defining
      the network nodes and extracting their associated timeseries) is extremely
      damaging to network estimation; hence, results derived from inappropriate ROI
      definition (such as via structural atlases) should be regarded with great
      caution.

PMID- 20817104
TI  - Brain atrophy correlates with functional outcome in a murine model of multiple
      sclerosis.
AB  - White matter (WM) lesions are the classic pathological hallmarks of multiple
      sclerosis (MS). However, MRI-based WM lesion load shows relatively poor
      correlation with functional outcome, resulting in the "clinico-radiological
      paradox" of MS. Unlike lesion based measures, volumetric MRI assessment of brain
      atrophy shows a strong correlation with functional outcome, and the presence of
      early atrophy predicts a worse disease course. While extensive literature exists
      describing MRI characteristics of atrophy in MS, the exact pathogenesis and the
      substrate of atrophy-gray vs. WM loss, axonal/neuronal damage vs. demyelination,
      or a combination of the above-remain unclear. Animal models of atrophy would
      allow for detailed investigations of the pathomechanism, and would contribute to
      an enhanced understanding of structural-functional connections in this complex
      disease. We now report that in the Theiler's Murine Encephalitis Virus (TMEV)
      model of MS in SJL/J mice, significant brain atrophy accompanies the development
      of the progressive MS-like disease. We conducted volumetric MRI studies in 8
      cases and 4 age, gender- and strain-matched control mice. While in controls we
      did not detect any brain atrophy, significant atrophy developed as early as 3
      months into the disease course, and reached its peak by 6 months, resulting in
      ventricular enlargement by 118% (p=0.00003). A strong correlation (r=-0.88)
      between atrophy and disability, as assessed by rotarod assay, was also
      demonstrated. We earlier reported another neurodegenerative feature in this
      model, the presence of deep gray matter T2 hypointensity in thalamic nuclei.
      Future studies utilizing this model will allow us to investigate key components
      of MRI detectable neurodegenerative feature development, their tissue
      correlations and associations with functional outcome measures. These studies are
      expected to pave the way to a better understanding of the substrate of disability
      in MS models.

PMID- 20817105
TI  - Medial prefrontal gray matter volume reductions in users of amphetamine-type
      stimulants revealed by combined tract-based spatial statistics and voxel-based
      morphometry.
AB  - Amphetamine-type stimulants (ATS) refer to a group of drugs whose principal
      members include amphetamine, methamphetamine and 3,4
      methylenedioxymethamphetamine (MDMA). Worldwide, ATS are among the most common
      illicit drugs. Therefore, understanding whether and to what extent ATS exposure
      affects brain structure and functioning in recreational users has become a
      critical public health issue. We studied gray and white matter densities in 20
      experienced users of ATS (more than 100 units MDMA and/or 50 g of amphetamine
      lifetime dose), 42 low exposure users with very limited ATS experience (less than
      5 units lifetime dose) and 16 drug-naive controls. A tract-based spatial
      statistics (TBSS) analysis of fractional anisotropy images was applied to
      diffusion magnetic resonance imaging (MRI) data. Furthermore, alignment invariant
      white matter tract representations acquired from the TBSS analysis were used as a
      reference for inter-subject brain registrations in a voxel-based morphometry
      (VBM) analysis of gray matter volume, reducing characteristic alignment
      inaccuracies associated with this voxel-wise gray matter investigation approach.
      Between-group white matter comparison revealed no significant results. However,
      compared to low exposure users, experienced users showed several regions of lower
      gray matter volume in medial frontal regions, in particular the orbital and
      medial frontal cortex. Differences are likely to reflect effects of repeated ATS
      exposure even in recreational users. However, differences in pre-existing or
      confounding factors might also account for between-group differences.

PMID- 20817106
TI  - Projecting memories: the role of the hippocampus in emotional mentalizing.
AB  - Humans have a striking tendency to use past autobiographical events to understand
      their own behavior. However, it is unknown if we use our own memories to
      understand others. To assess the role of autobiographical memory in mentalizing
      we examined the contribution of memory structures, specifically the hippocampus,
      to emotional judgment of others. Subjects were scanned while making emotional
      judgments regarding themselves, and protagonists deemed similar to or dissimilar
      from themselves. Results indicated a significant correlation between rating of
      the self and the similar protagonists, particularly for the events subjects
      recalled from their past. Furthermore, we found an interaction between similarity
      and recollection so that only for events subjects recalled from their past, the
      hippocampus reacted differently for judgments regarding the self versus
      dissimilar others, but not for self versus similar others. These results suggest
      that people actually use their own repertoire of memories and project internal
      self knowledge while making emotional judgments regarding others. It is
      speculated that mentalizing is modulated by memories of similar past events and
      depends on the protagonist we face.

PMID- 20817107
TI  - The impact of certain methodological choices on multivariate analysis of fMRI
      data with support vector machines.
AB  - Multivoxel pattern analysis of functional magnetic resonance imaging (fMRI) data
      is continuing to increase in popularity. Like all fMRI analyses, these analyses
      require extensive data processing and methodological choices, but the impact of
      these decisions on the final results is not always known. This study explores the
      impact of four methodological choices on analysis outcomes and introduces the
      technique of partitioning on random runs for characterizing temporal dependencies
      and evaluating partitioning methods. The analyses were performed on two fMRI data
      sets, which were repeatedly analyzed with support vector machines, varying the
      method of temporal compression, smoothing, voxel-wise detrending, and
      partitioning into training and testing sets. Smoothing sometimes slightly
      increased classification accuracy. Partitioning other than on the runs increased
      classification accuracy, and the random runs technique allowed us to attribute
      this improvement to the increased amount of training data, rather than to bias.
      The impact of the temporal compression and detrending methods varied so strongly
      with data set that general recommendations could not be drawn. These interactions
      suggest that, rather than searching for a universally superior set of
      methodological choices, researchers must carefully consider each choice in the
      context of each experiment.

PMID- 20817108
TI  - Population genetic structure of Cichla pleiozona (Perciformes: Cichlidae) in the
      Upper Madera basin (Bolivian Amazon): sex-biased dispersal?
AB  - This study investigates the population structure of the Tucunare (Cichla
      pleiozona) in the Bolivian Amazon (Upper Madera) by using nuclear (EPIC-PCR, 67
      individuals) and mitochondrial (Control Region, 41 published and 76 new
      sequences) DNA analyses, in relation with ecological (water quality: muddy, clear
      and mix) and geographic factors. Our analyses of both markers showed the highest
      diversity in clear waters (Yata, Middle and Upper Itenez), and the existence of
      two populations in muddy waters (Secure and Ichilo) and one in mix waters
      (Manuripi). On the other hand, mitochondrial analyses identified three
      populations in clear waters where nuclear analyses identified a panmictic
      population. The highest diversity observed in the Yata-Itenez system suggests
      that an aquatic refuge occurred during the past in this area. The possible
      explanations for the observed discrepancy between nuclear and mitochondrial
      markers are discussed, and a sex-biased dispersal seems to be the most plausible
      hypothesis in the light of the available information and field observations.

PMID- 20817109
TI  - The phylogenetic position of Neritimorpha based on the mitochondrial genome of
      Nerita melanotragus (Mollusca: Gastropoda).
AB  - This is the first report of the mitochondrial gene order and almost-complete DNA
      sequence of a representative of the Neritimorpha, the highest-ranking gastropod
      clade lacking such data. Mitochondrial gene order in Nerita is largely
      plesiomorphic. Its only difference from the cephalopod Octopus vulgaris is a tRNA
      transposition shared by Vetigastropoda and Caenogastropoda. Genome arrangements
      were not informative enough to resolve the evolutionary relationships of
      Neritimorpha, Vetigastropoda and Caenogastropoda. The sister-group taxon of
      Neritimorpha varied in sequence-based analyses. Some suggested that Neritimorpha
      is the sister group of Caenogastropoda plus Heterobranchia and some that
      Neritimorpha and Caenogastropoda are sister groups. No analysis significantly
      supported the hypothesis that Vetigastroda is more closely related to
      Caenogastropoda than is Neritimorpha.

PMID- 20817110
TI  - Towards a molecular phylogeny of Mollusks: bivalves' early evolution as revealed
      by mitochondrial genes.
AB  - Despite huge fossil, morphological and molecular data, bivalves' early
      evolutionary history is still a matter of debate: recently, established phylogeny
      has been mostly challenged by DNA studies, and little agreement has been reached
      in literature, because of a substantial lack of widely-accepted methodological
      approaches to retrieve and analyze bivalves' molecular data. Here we present a
      molecular phylogeny of the class based on four mitochondrial genes (12s, 16s,
      cox1, cytb) and a methodological pipeline that proved to be useful to obtain
      robust results. Actually, best-performing taxon sampling and alignment strategies
      were tested, and several data partitioning and molecular evolution models were
      analyzed, thus demonstrating the utility of Bayesian inference and the importance
      of molding and implementing non-trivial evolutionary models. Therefore, our
      analysis allowed to target many taxonomic questions of Bivalvia, and to obtain a
      complete time calibration of the tree depicting bivalves' earlier natural history
      main events, which mostly dated in the late Cambrian.

PMID- 20817111
TI  - Childhood obesity and outcomes after bone marrow transplantation for patients
      with severe aplastic anemia.
AB  - The prevalence of obesity in the pediatric population has increased in the last 2
      decades and represents a serious health concern, with potential impact on
      outcomes of hematopoietic cell transplantation (HCT). We studied the effect of
      weight by age-adjusted body mass index (BMI) percentile in 1,281 pediatric
      patients (age 2-19 years) with severe aplastic anemia who underwent HCT between
      1990 and 2005. The study population was divided into 5 weight groups-underweight,
      risk of underweight, normal BMI range, risk of overweight, and overweight
      according to age-adjusted BMI percentiles. Cox proportional hazards regression
      models for survival and acute graft-versus-host disease (aGVHD), performed using
      weight groups as the main effect and the normal BMI range (26th-75th percentile)
      as the baseline comparison, found higher mortality among overweight children
      (>95th percentile adjusted for age). Weight at transplantation did not increase
      the adjusted risk of grade III-IV aGVHD. The 1-year and 2-year overall survival
      rates were 60% and 59% for overweight children, compared with >70% in children
      with lower BMI at both time points (P < .001). Other significant factors
      associated with survival included race and region, donor type, conditioning
      regimens in related donor transplants, performance score, and year of
      transplantation. In conclusion, overweight children with aplastic anemia have
      worse outcomes after HCT. The impact of obesity on survival outcomes in children
      should be discussed during pretransplantation counseling.

PMID- 20817112
TI  - Molecular mechanisms in renal degenerative disease.
AB  - Chronic kidney disease (CKD) has become a major public health problem worldwide.
      Therefore, a considerable effort is currently directed to understand the
      molecular mechanisms of renal degenerative processes. Regardless of their
      initiating cause, all chronic kidney diseases (CKD) develop at some level organ
      fibrosis that interferes with kidney function. This is also true for the two most
      common inherited CKD syndromes, nephronophthitis and polycystic kidney disease,
      whose primary defects reside within the cilium of kidney epithelial cells. A
      cohort of elegant recent studies has elicited the role of the primary cilium as a
      versatile mechanosensory organelle that also might coordinate cross-talk between
      multiple signaling pathways. In addition, epigenetic mechanisms are now realized
      to be essential in the maintenance of adult renal architecture. In this review,
      we will discuss recent advances in our understanding of the signaling systems
      implicated in kidney homeostasis and repair.

PMID- 20817113
TI  - Functional analysis and subcellular location of two flavohemoglobins from
      Aspergillus oryzae.
AB  - Multiple flavohemoglobin (FHb) homolog genes are found in the genomes of
      eukaryotic microorganisms, but their functions remain unknown. In this study, two
      distinct types of FHbs (predictive cytosolic FHb1 and predictive mitochondrial
      FHb2) from the fungus Aspergillus oryzae were investigated to elucidate the
      physiological roles of these FHbs. The fhb1 gene responded to external nitric
      oxide (NO) stress at the transcriptional level, whereas the fhb2 gene did not.
      Disrupting fhb1 increased cell hypersensitivity to NO stress, whereas deficiency
      of the fhb2 gene had no effect on phenotype compared to the wild-type strain. By
      fusing GFP protein to FHbs, we determined that FHb1 and FHb2 are located in the
      cytosol and mitochondria, respectively. In the wild-type strain, the
      transcriptional level of the fhb2 gene was too low to be detected, but its
      expression was detectable in the NirK (mitochondrial copper-containing
      dissimilatory nitrite reductase) overexpression strain (AoHnirK), which showed a
      significantly higher denitrification capability than that shown by the wild-type
      strain. The induction of the fhb2 gene in the AoHnirK strain may be due to the
      abundance of NO produced by overexpressed NirK in the mitochondria. These results
      suggest that FHb1 and FHb2 may play a role in protecting cells from external and
      internal NO stress, respectively.

PMID- 20817114
TI  - Activation of the heat shock transcription factor Hsf1 is essential for the full
      virulence of the fungal pathogen Candida albicans.
AB  - The evolutionarily conserved heat shock transcription factor Hsf1 plays a central
      role in thermal adaptation in the major fungal pathogen of humans, Candida
      albicans. Hsf1 becomes hyperphosphorylated in response to heat shock and
      activates the transcription of genes with heat shock elements (HSEs) in their
      promoters, these genes contributing to thermal adaptation. However, the relevance
      of Hsf1 activation to C. albicans virulence is not clear as this pathogen is
      thought to be obligately associated with warm blooded animals, and this issue has
      not been tested because HSF1 is essential for viability in C. albicans. In this
      study, we demonstrate that the HSE regulon is active in C. albicans cells
      infecting the kidney. We also show the CE2 region of Hsf1 is required for
      activation and that the phosphorylation of specific residues in this domain
      contributes to Hsf1 activation. C. albicans HSF1 mutants that lack this CE2
      region are viable. However, they are unable to activate HSE-containing genes in
      response to heat shock, and they are thermosensitive. Using this HSF1 CE2
      deletion mutant we demonstrate that Hsf1 activation, and hence thermal
      adaptation, contributes significantly to the virulence of C. albicans.

PMID- 20817115
TI  - Characterization of the developmental regulator FlbE in Aspergillus fumigatus and
      Aspergillus nidulans.
AB  - Several upstream developmental activators control asexual development
      (conidiation) in Aspergillus. In this study, we characterize one of such
      activators called flbE in Aspergillus fumigatus and Aspergillus nidulans. The
      predicted FlbE protein is composed of 222 and 201 aa in A. fumigatus and A.
      nidulans, respectively. While flbE is transiently expressed during early phase of
      growth in A. nidulans, it is somewhat constitutively expressed during the
      lifecycle of A. fumigatus. The deletion of flbE causes reduced conidiation and
      delayed expression of brlA and vosA in both species. Moreover, FlbE is necessary
      for salt-induced development in liquid submerged culture in A. fumigatus. The A.
      nidulans flbE null mutation is fully complemented by A. fumigatus flbE,
      indicating a functional conservancy of FlbE in Aspergillus. Both the deletion and
      overexpression of flbE in A. nidulans result in developmental defects, enhanced
      autolysis, precocious cell death, and delayed expression of brlA/vosA, suggesting
      that balanced activity of FlbE is crucial for proper growth and development.
      Importantly, the N-terminal portion of FlbE exhibits the trans-activation ability
      in yeast, whereas the C-terminal half negatively affects its activity. Site
      directed mutagenesis of certain conserved N-terminal amino acids abolishes the
      ability of trans-activation, overexpression-induced autolysis, and complementing
      the null mutation. Finally, overexpression of flbD, but not flbB or flbC,
      restores conidiation in A. nidulans DeltaflbE, generally supporting the current
      genetic model for developmental regulation.

PMID- 20817116
TI  - The role of 20-hydroxyecdysone signaling in Drosophila pupal metabolism.
AB  - In holometabolous insects, the steroid hormone 20-hydroxyecdysone (20E), in
      coordination with juvenile hormone, regulates the major developmental events that
      promote larval development and the transition from the larval to the pupal stage.
      Intimately entwined with the hormonal control of development is the control of
      larval growth and the acquisition of energy stores necessary for the development
      of the non-feeding pupa and immature adult. Studies of the coordination of insect
      development and growth have suggested that the larval fat body plays a central
      role in monitoring animal size and nutritional status by integrating 20E
      signaling with the insulin signaling pathway. Previous studies have shown that
      tissue-specific loss of 20E signaling in the fat body causes pupal lethality
      (Cherbas et al., 2003). Because the fat body is the major organ responsible for
      nutrient homeostasis, we hypothesized that the observed pupal mortality is due to
      a metabolic defect. In this paper we show that disruption of 20E signaling in the
      fat body does not disrupt nutrient storage, animal size at pupariation, or
      nutrient utilization. We conclude that 20E signaling in the fat body is not
      necessary for normal pupal metabolism.

PMID- 20817117
TI  - Effects of early neonatal development and delayed feeding immediately post-hatch
      on the hepatic lipogenic program in broiler chicks.
AB  - The embryo to neonate transition is a critical period of development that has
      significant impact on broiler production. During this time important genetic
      programs governing metabolism and growth are established. The goal of this work
      was to study the effects of early post-hatch (PH) development and the time of
      initiation of feeding on activation of the genetic program regulating hepatic
      lipogenesis. A comparison of liver total RNA samples at hatch and 7 days PH was
      performed using oligonucleotide-based (Affymetrix GeneChip(r)) chicken genome
      microarrays. During the first week PH there was significant up-regulation of key
      lipogenic genes including: ATP citrate lyase (ACL), malic enzyme (ME), fatty acid
      synthase (FAS), acetyl-CoA carboxylase alpha (ACCalpha), stearoyl-CoA desaturase
      1 (SCD-1), sterol regulatory element binding protein-2 (SREBP-2) and thyroid
      hormone responsive spot 14alpha (Spot 14alpha) among others. These findings were
      confirmed using gene-specific RT-PCR assays. In a follow-up study, we
      investigated the effects of withholding feed for the first 48 h PH (delayed
      feeding, DF) on lipogenic gene expression through 8 days PH. Body weight gain was
      significantly depressed by DF. Plasma levels of the major metabolic hormones that
      regulate lipogenic gene expression (insulin, glucagon and T(3)) changed
      significantly during PH development, but were largely unaffected by DF. Plasma
      glucose was significantly lower in the DF group at 24h PH but recovered
      thereafter. In general, DF inhibited the up-regulation of lipogenic genes until
      feeding was initiated. Delayed up-regulation was also observed for the lipogenic
      transcription factor genes, SREBP-1, SREBP-2 and peroxisome proliferator
      activated receptor gamma (PPARgamma), but not for carbohydrate response element
      binding protein (ChREB) or liver X receptor (LXR). Our results offer additional
      insight into the transcriptional programming of hepatic lipogenesis in response
      to the transition from high fat (yolk) to high carbohydrate (feed) nutrition that
      occurs during early PH development.

PMID- 20817118
TI  - Isolation and cDNA cloning of type 2 sodium channel peptide toxins from three
      species of sea anemones (Cryptodendrum adhaesivum, Heterodactyla hemprichii and
      Thalassianthus aster) belonging to the family Thalassianthidae.
AB  - The crude extracts from three species of sea anemones (Cryptodendrum adhaesivum,
      Heterodactyla hemprichii and Thalassianthus aster) belonging to the family
      Thalassianthidae exhibited potent lethality to freshwater crabs (Potamon
      dehaani). Regardless of the species, high and low molecular weight toxins were
      found in gel filtration of the crude extract. Following reverse-phase HPLC of the
      low molecular weight toxin fractions, one toxin (delta-TLTX-Ca1a), two toxins
      (delta-TLTX-Hh1a and c) and one toxin (delta-TLTX-Ta1a) were isolated from C.
      adhaesivum, H. hemprichii and T. aster, respectively. Based on the determined N
      terminal amino acid sequences, the cDNAs encoding delta-TLTX-Ca1a, delta-TLTX
      Hh1x (not assignable to either delta-TLTX-Hh1a or delta-TLTX-Hh1c) and delta-TLTX
      Ta1a were successfully cloned by both 3' and 5' RACE methods. In common with the
      three toxins, the precursor is composed of a signal peptide (19 amino acid
      residues), propart (16 residues) and mature portion (49 residues), similar to
      those of many sea anemone peptide toxins. The deduced amino acid sequences showed
      that the three toxins are closely similar to one another, being all new members
      of the type 2 sea anemone sodium channel peptide toxin family.

PMID- 20817119
TI  - Interleukin-21: a multifunctional regulator of immunity to infections.
AB  - Interleukin-21 (IL-21) is a cytokine that has broad effects on both innate and
      adaptive immune responses. The roles of IL-21 in determining immunity to
      infections are currently being defined, and notably, it has been shown that IL-21
      is most critical for sustaining T cell responses during chronic viral infections.
      This article discusses our current understanding of the immunobiology of IL-21,
      as well as its known and potential roles in influencing immunity to infections.

PMID- 20817120
TI  - Loxoribine, a selective Toll-like receptor 7 agonist, induces maturation of human
      monocyte-derived dendritic cells and stimulates their Th-1- and Th-17-polarizing
      capability.
AB  - Recently, a guanosine analog, 7-allyl-7,8-dihydro-8-oxo-guanosine (loxoribine),
      has been identified as a selective Toll-like receptor (TLR)7 agonist. Bearing in
      mind the controversy regarding the expression of TLR7 by human myeloid dendritic
      cells (DCs) and its significance for functions of these cells, the goal of this
      study was to investigate the effect of loxoribine on differentiation, maturation
      and functions of human monocyte-derived (Mo)DCs. Immature MoDCs were obtained by
      cultivation of monocytes for 6 days with recombinant granulocyte macrophage
      colony stimulating factor (GM-CSF) and interleukin (IL)-4. These cells were
      stimulated with loxoribine (250 MUM) for an additional 48 h. Phenotypic
      properties of MoDCs were determined by flow cytometry, cytokine production was
      assayed by ELISA, whereas their allostimulatory capability was tested using a
      mixed leukocyte reaction. We showed that loxoribine up-regulated the expression
      of TLR7, CD40, CD54, CD80, CD83 and CCR7 and stimulated the production of IL-12,
      IL-23, IL-27 and IL-10 by MoDCs, whereas the level of interferon (IFN)-beta was
      not modulated. Allogeneic CD4(+)T cells in co-culture with loxoribine-treated
      MoDCs proliferated more strongly, at lower DC/CD4(+)T-cell ratio (1:80), and
      secreted significantly higher levels of IL-17 and IFN-gamma compared to the
      cultures with control MoDCs. The stimulatory effect of loxoribine on T helper
      (Th)1 polarization capability of MoDCs was further potentiated by ligation of
      CD40. In conclusion, our results show that loxoribine stimulated differentiation,
      maturation, allostimulatory as well as Th1 and Th17 polarization capability of
      human MoDCs and suggests that these effects might be associated with up
      regulation of TLR7 expression, but not increased IFN-beta production.

PMID- 20817121
TI  - Gene silencing in Echinococcus multilocularis protoscoleces using RNA
      interference.
AB  - We investigated the potential of gene silencing in Echinococcus multilocularis
      protoscoleces using RNA interference (RNAi). For the introduction of siRNA,
      soaking and electroporation were first examined for their effects on the
      viability of protoscoleces and their efficacy for siRNA introduction.
      Consequently, electroporation using 100 V and 800 MUF showed the optimal results.
      This electroporation procedure was then evaluated for its ability to induce RNAi
      in protoscoleces using siRNAs targeting the 14-3-3 and elp genes. It was found
      that the levels of 14-3-3 and elp mRNA in 14-3-3 siRNA- and elp siRNA-treated
      protoscoleces were reduced to 21.8 +/- 2.6 and 35.5 +/- 0.4% of those of the
      untreated control by day 3, respectively. Moreover, the target proteins
      significantly decreased in the siRNA-treated samples by day 15. In the analysis
      of viability, the untreated control, electroporation control, 14-3-3 siRNA
      treated, and elp siRNA-treated samples displayed 98.4 +/- 1.4, 83.0 +/- 2.5, 58.0
      +/- 23.0, and 55.1 +/- 14.6% viability, respectively, on day 15. In conclusion,
      we successfully demonstrated that RNAi mediated the knock-down of target gene
      expression in E. multilocularis protoscoleces at both the transcriptional and
      translational levels.

PMID- 20817122
TI  - Altered lipoprotein metabolism in P2Y(13) knockout mice.
AB  - The purinergic receptor P2Y(13) has been shown to play a role in the uptake of
      holo-HDL particles in in vitro hepatocyte experiments. In order to determine the
      role of P2Y(13) in lipoprotein metabolism in vivo, we ablated the expression of
      this gene in mice. Here we show that P2Y(13) knockout mice have lower fecal
      concentrations of neutral sterols (-27%+/-2.1% in males) as well as small
      decreases in plasma HDL (-13.1%+/-3.2% in males; -17.5%+/-4.0% in females)
      levels. In addition, significant decreases were detected in serum levels of fatty
      acids and glycerol in female P2Y(13) knockout mice. Hepatic mRNA profiling
      analyses showed increased expression of SREBP-regulated cholesterol and fatty
      acid biosynthesis genes, while fatty acid beta-oxidation genes were significantly
      decreased. Liver gene signatures also identified changes in PPARalpha-regulated
      transcript levels. With the exception of a small increase in bone area, P2Y(13)
      knockout mice do not show any additional major abnormalities, and display normal
      body weight, fat mass and lean body mass. No changes in insulin sensitivity and
      oral glucose tolerance could be detected. Taken together, our experiments assess
      a role for the purinergic receptor P2Y(13) in the regulation of lipoprotein
      metabolism and demonstrate that modulating its activity could be of benefit to
      the treatment of dyslipidemia in people.

PMID- 20817123
TI  - Characterization of nanoprobe uptake in single cells: spatial and temporal
      tracking via SERS labeling and modulation of surface charge.
AB  - A critical aspect for use of nanoprobes in biomedical research and clinical
      applications involves fundamental spatial and temporal characterization of their
      uptake and distribution in cells. Raman spectroscopy and two-dimensional Raman
      imaging were used to identify and locate nanoprobes in single cells using surface
      enhanced Raman scattering detection. To study the efficiency of cellular uptake,
      silver nanoparticles functionalized with three different positive-, negative-,
      and neutrally charged Raman labels were co-incubated with cell cultures and
      internalized via normal cellular processes. The surface charge on the
      nanoparticles was observed to modulate uptake efficiency, demonstrating a dual
      function of the surface modifications as tracking labels and as modulators of
      cell uptake. These results indicate that the functionalized nanoparticle
      construct has potential for sensing and delivery in single living cells and that
      use of surface-enhanced Raman scattering for tracking and detection is a
      practical and advantageous alternative to traditional fluorescence methods. FROM
      THE CLINICAL EDITOR: Cell labeling and tracking methods are commonly required in
      biomedical research. This paper presents specific functionalized nanoparticle
      constructs with potential for sensing and delivery in single living cells. The
      use of surface-enhanced Raman scattering enables tracking and detection of these
      cells as a practical alternative to traditional fluorescence methods.

PMID- 20817124
TI  - HSV-TK/GCV cancer suicide gene therapy by a designed recombinant multifunctional
      vector.
AB  - The objective of this research was to evaluate the efficacy of a recombinant
      nonviral vector for targeted delivery of a thymidine kinase (TK) suicide gene to
      xenograft SKOV-3 tumors. The vector was genetically engineered and used to
      condense the TK gene into particles of less than 100 nm. The nanoparticles were
      used to transfect and kill SKOV-3 cancer cells in combination with ganciclovir
      (GCV) in vitro. The results demonstrated that the vector could effectively kill
      up to 80% of the SKOV-3 cancer cells. In the next step, the ability of the vector
      to deliver the TK suicide gene to xenograft tumors of SKOV-3 was studied. The
      results demonstrated that the vector could transfect tumors and result in
      significant tumor size reduction during the period that GCV was administered.
      Administration of GCV for at least 3 weeks post transfection was of paramount
      importance. These results illustrate the therapeutic efficacy and application of
      a designed recombinant nonviral vector in cancer gene therapy. FROM THE CLINICAL
      EDITOR: A recombinant nonviral vector is used to deliver a suicide thymidine
      kinase gene under gancylovir control in vitro to SKOV-3 cancer cells with 70%
      efficiency. Follow on testing in a xenograft tumor demonstrated tumor reduction
      persisting for three weeks.

PMID- 20817125
TI  - Curcumin nanodisks: formulation and characterization.
AB  - Nanodisks (NDs) are nanoscale, disk-shaped phospholipid bilayers whose edge is
      stabilized by apolipoproteins. In the present study, NDs were formulated with the
      bioactive polyphenol curcumin at a 6:1 phospholipid-to-curcumin molar ratio.
      Atomic force microscopy revealed that curcumin-NDs are particles with diameters
      <50 nm and the thickness of a phospholipid bilayer. When formulated in NDs,
      curcumin is water soluble and gives rise to a characteristic absorbance spectrum
      with a peak centered at 420 nm. Fluorescence spectroscopy of curcumin-NDs
      provided evidence of self-quenching. Incubation of curcumin-NDs with empty NDs
      relieved the self-quenching, indicating redistribution of curcumin between
      curcumin-loaded and empty NDs. In HepG2 cells, curcumin-NDs mediated enhanced
      cell growth inhibition as compared with free curcumin. In a cell culture model of
      mantle cell lymphoma, curcumin-NDs were a more potent inducer of apoptosis than
      free curcumin. The nanoscale size of the complexes, combined with their ability
      to solubilize curcumin, indicates NDs may have in vivo therapeutic applications.
      FROM THE CLINICAL EDITOR: Nanodisks (NDs), disk-shaped phospholipid bilayers
      stabilized by apolipoproteins, are shown entrap curcumin and improve its delivery
      to HepG2 and mantle cell lymphoma cells in culture. These novel nanocomplexes
      demonstrate interesting therapeutic application potentials.

PMID- 20817126
TI  - Nanoprobing of alpha-synuclein misfolding and aggregation with atomic force
      microscopy.
AB  - Atomic force microscopy (AFM) force spectroscopy is a technique with broad
      nanomedical applications, widely used for the characterization of molecular
      interactions on the nanoscale. Here we test this technique to evaluate compounds
      for influencing the protein aggregation process. The results demonstrate that
      Zn(2+) or Al(3+) cations bring about a dramatic increase of alpha-synuclein
      interactions in unfavorable conditions for alpha-synuclein misfolding (neutral
      pH). We did not observe the effect of dopamine at favorable conditions for alpha
      synuclein misfolding (acidic pH). We also found that electrostatic interactions
      do not play a significant role at acidic pH. These findings are generally in line
      with previous studies by various techniques. The high sensitivity of AFM force
      spectroscopy as well as its ability to test compounds for the same experimental
      system makes AFM an efficient nanotool for rapid analysis of compounds inhibiting
      early protein aggregation studies and quantitative selection of potential
      therapeutics for neurodegenerative diseases. FROM THE CLINICAL EDITOR: Atomic
      force microscopy is used to interrogate the influence of cations and alpha
      synuclein on the protein aggregation process. The report illustrates an
      application of AFM to unravel the potential of novel therapeutics on early
      protein aggregation intrinsic in neurodegenerative diseases.

PMID- 20817127
TI  - Autoimmunity and chronic inflammation - two clearance-related steps in the
      etiopathogenesis of SLE.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease with very prominent
      chronic inflammatory aspects that render into multiple symptoms and clinical
      signs. The precise etiology of SLE remains elusive; however, it is known that its
      etiopathogenesis is of multifactorial nature. The production of autoantibodies
      (AAb) targeting double stranded DNA (dsDNA) and other nuclear autoantigens is the
      main characteristic of this disease. These target antigens are often modified
      and/or translocated when apoptotic cells undergo secondary necrosis as a
      consequence of the clearance deficiency in patients with SLE. In healthy
      individuals, dead and dying cells are rapidly removed by macrophages in an anti
      inflammatory context; this does not elicit immune responses. In SLE, apoptotic
      cells are often not properly cleared; autoantigens leak out, and are subsequently
      presented to B cells by follicular dendritic cells (FDC) in secondary lymphoid
      tissues. This defect challenges the peripheral self-tolerance. Autoreactive B
      cell activation and production of anti-nuclear AAb result as the first step in
      the etiopathogenesis of SLE. The second step is the formation of immune complexes
      (IC) with apoptotic cell-derived nuclear remnants either in situ or deposited in
      various tissues. Nucleic acid-containing IC may also be ingested by phagocytes,
      which subsequently produce pro-inflammatory cytokines. Both processes result in
      chronic organ and tissue damage, development and maintenance of the systemic
      autoimmune disease. In conclusion, clearance deficiency may contribute to SLE in
      two ways: first, in germinal centres it enables the affinity maturation of
      autoreactive B cells and second, in peripheral tissues it leads to the
      accumulation of accessible nuclear autoantigens. Chronic inflammation in SLE is
      consequently promoted by the persistently binding of AAb with their cognate
      autoantigens forming a binary weapon: the nucleic acid-containing IC.

PMID- 20817128
TI  - Random field assessment of nanoscopic inhomogeneity of bone.
AB  - Bone quality is significantly correlated with the inhomogeneous distribution of
      material and ultrastructural properties (e.g., modulus and mineralization) of the
      tissue. Current techniques for quantifying inhomogeneity consist of descriptive
      statistics such as mean, standard deviation and coefficient of variation.
      However, these parameters do not describe the spatial variations of bone
      properties. The objective of this study was to develop a novel statistical method
      to characterize and quantitatively describe the spatial variation of bone
      properties at ultrastructural levels. To do so, a random field defined by an
      exponential covariance function was used to represent the spatial uncertainty of
      elastic modulus by delineating the correlation of the modulus at different
      locations in bone lamellae. The correlation length, a characteristic parameter of
      the covariance function, was employed to estimate the fluctuation of the elastic
      modulus in the random field. Using this approach, two distribution maps of the
      elastic modulus within bone lamellae were generated using simulation and compared
      with those obtained experimentally by a combination of atomic force microscopy
      and nanoindentation techniques. The simulation-generated maps of elastic modulus
      were in close agreement with the experimental ones, thus validating the random
      field approach in defining the inhomogeneity of elastic modulus in lamellae of
      bone. Indeed, generation of such random fields will facilitate multi-scale
      modeling of bone in more pragmatic details.

PMID- 20817129
TI  - Calcium supplementation does not rescue the programmed adult bone deficits
      associated with perinatal growth restriction.
AB  - Low birth weight and poor childhood growth program a variety of adult diseases
      including bone disorders such as osteoporosis. We have previously reported that
      offspring born small, as a result of uteroplacental insufficiency, have shorter
      femurs, lower bone mineral content and a bone strength deficit as adults. The aim
      of this study was to determine the effects of calcium supplementation from
      adolescence on growth restricted male and female offspring which have a
      programmed bone deficit. Bilateral uterine vessel ligation (Restricted) or sham
      surgery (Control) was performed on gestational day 18 in WKY rats to induce
      uteroplacental insufficiency and growth restriction. At 2 months pups were
      allocated to one of four diet groups: diet 1-constant normal calcium diet, diet 2
      variable normal calcium diet, diet 3-constant high calcium diet, diet 4-variable
      high calcium diet. Diet groups 1 and 3 were fed their respective diets constantly
      for the duration of the study. In groups 2 and 4, rats were fed one diet for 5
      days, followed by a switch to a low calcium diet for the next 5 days. At 6 months
      Dual Energy Xray Absorptiometry (DXA) and Peripheral Quantitative Computed
      Tomography (pQCT) were performed on the right femur. Bone turnover markers were
      measured at 4 months. Male and female Restricted offspring were born 14% lighter
      compared to Controls (p<0.05). At 6 months both male and female Restricted
      offspring remained smaller and had shorter femurs compared to Controls (p<0.05).
      Restricted males and females had reduced trabecular and cortical content compared
      to Controls, regardless of diet (p<0.05). Trabecular bone density was lower in
      Restricted females only (p<0.05). A constant high calcium diet increased cortical
      BMD in Restricted male and both female groups (p<0.05). Measures of bone geometry
      indicated that Restricted offspring have narrower bones with preservation of
      absolute cortical thickness (p<0.05). Importantly, the stress strain index of
      bone bending strength was lower in male and female Restricted offspring,
      regardless of diet by up to 9.0% and 7.8%, respectively. DXA results were similar
      to pQCT results. Being born small, due to uteroplacental insufficiency, programs
      reduced adult femur length, dimensions and stress strain index. Supplementation
      with a high calcium diet from adolescence can increase adult cortical bone
      density in low birth weight males and females, and normal weight females. This
      increase in bone density was not sufficient to rescue the bone dimension and
      strength deficits which were programmed in utero, suggesting that the early life
      environment is critical for bone programming.

PMID- 20817130
TI  - Short-term activation of liver X receptors inhibits osteoblasts but long-term
      activation does not have an impact on murine bone in vivo.
AB  - Liver X receptors (LXRs) are nuclear receptors that play a crucial role in the
      transcriptional control of lipid metabolism. Pharmacological LXR activation is an
      attractive concept for the treatment of atherosclerosis. Genetic LXR deficiency
      in mice has been shown to have an effect on bone turnover and structure and LXR
      activation is known to influence the osteogenic differentiation of bone marrow
      stromal cells. Therefore, therapeutic pharmacological LXR activation may have
      relevant effects on bone. Here, using two synthetic LXR ligands, T0901317 and
      GW3965, we investigated the effect of LXR activation on murine osteoblasts and
      the influence of long-term LXR activation on bone in vivo in mice. Short term (48
      h) in vitro treatment of primary murine osteoblasts with T0901317 resulted in a
      dose-dependent decrease of osteocalcin and alkaline phosphatase mRNA and protein.
      In vivo, a 6-day treatment of C57BL/6J mice with T0901317 led to a 40% reduction
      of serum osteocalcin concentrations. Long-term (12-week) oral administration of
      T0901317 or GW3965 influenced the expression of established LXR target genes in
      liver and intestine, but did not alter trabecular and cortical bone structure or
      bone turnover as determined by total skeleton radiography, histomorphometric
      analysis of lumbar vertebral trabecular bone, micro CT analysis of femur cortical
      bone and biochemical determination of bone formation and resorption markers. We
      conclude that short-term pharmacological LXR activation has the potential to
      profoundly influence osteoblast function, but that long-term LXR activation in
      vivo has no adverse effects on the murine skeleton.

PMID- 20817131
TI  - Age of acquisition effects in vocabulary learning.
AB  - Two experiments examined whether the age of acquisition (AoA) of a concept
      influences the speed at which native English speakers are able to name pictures
      using a newly acquired second language (L2) vocabulary. In Experiment 1,
      participants were taught L2 words associated with pictures. In Experiment 2 a
      second group of participants were taught the same words associated with L1
      translations. Following training both groups performed a picture naming task in
      which they were asked to name pictures using the newly acquired words.
      Significant AoA effects were observed only in Experiment 1, in that participants
      were faster at naming pictures representing early acquired relative to late
      acquired concepts. The results suggest that the AoA of a concept can exert
      influence over processing which is independent of the AoA of the word form. The
      results also indicate that different training methods may lead to qualitative
      differences in the nature of the links formed between words and concepts during
      the earliest stages of second language learning.

PMID- 20817133
TI  - Fear generalization in humans: Impact of prior non-fearful experiences.
AB  - Fear generalization lies at the heart of many anxiety problems, and is therefore
      an important target for prevention and/or treatment. Here, we investigated
      whether fear generalization towards a specific stimulus can be weakened by prior
      non-fearful experiences with that stimulus. Using the standard human fear
      conditioning procedure, all participants received paired presentations of a
      geometric figure and an electric shock. This was followed by a test phase in
      which a similar but different figure was presented. Electrodermal responding and
      ratings of shock-expectancy measured the level of fear generalization towards
      this test stimulus. Crucially, half of the participants had been preexposed to
      that stimulus (without shock). The results show significantly less generalization
      in this group, suggesting that prior non-fearful experiences can protect against
      fear generalization. These results may inspire novel ways to prevent the
      development of clinical anxiety.

PMID- 20817132
TI  - Secondary analysis of the use of transdermal nitroglycerin for preterm labor.
AB  - OBJECTIVE: This secondary analysis of a randomized placebo-controlled trial was
      to hypothesize on mechanisms for the improved neonatal outcomes with the use of
      nitroglycerin (GTN) for preterm labor. STUDY DESIGN: Women in the original trial
      who delivered at term were excluded. A composite of severe neonatal outcomes,
      gestational age at delivery, and corticosteroid use in addition to Kaplan-Meier
      survival analysis to assess time from randomization to delivery were examined.
      RESULTS: A decrease in composite neonatal outcome (relative risk, 0.21; 95%
      confidence interval, 0.05-0.81; P = .018) with GTN (n = 39) compared with placebo
      (n = 38) was primarily due to a 23 day prolongation of pregnancy (P = .019) and a
      trend (P = .04) toward completing a course of corticosteroids in the subgroup
      randomized prior to 28 weeks' gestation. CONCLUSION: We hypothesize that GTN has
      a gestational age-dependent reduction in neonatal outcomes as a result of
      pregnancy prolongation and corticosteroid administration.

PMID- 20817134
TI  - Looking, language, and memory: bridging research from the visual world and visual
      search paradigms.
AB  - In the visual world paradigm as used in psycholinguistics, eye gaze (i.e. visual
      orienting) is measured in order to draw conclusions about linguistic processing.
      However, current theories are underspecified with respect to how visual attention
      is guided on the basis of linguistic representations. In the visual search
      paradigm as used within the area of visual attention research, investigators have
      become more and more interested in how visual orienting is affected by higher
      order representations, such as those involved in memory and language. Within this
      area more specific models of orienting on the basis of visual information exist,
      but they need to be extended with mechanisms that allow for language-mediated
      orienting. In the present paper we review the evidence from these two different -
      but highly related - research areas. We arrive at a model in which working memory
      serves as the nexus in which long-term visual as well as linguistic
      representations (i.e. types) are bound to specific locations (i.e. tokens or
      indices). The model predicts that the interaction between language and visual
      attention is subject to a number of conditions, such as the presence of the
      guiding representation in working memory, capacity limitations, and cognitive
      control mechanisms.

PMID- 20817135
TI  - Incubation of cue-induced cigarette craving during abstinence in human smokers.
AB  - BACKGROUND: Abstinent drug users remain at risk for relapse long after withdrawal
      subsides. Animal studies indicate that responses to drug-related cues not only
      persist but increase with abstinence, a phenomenon termed "incubation of drug
      craving." It is unknown whether cue-induced craving increases, decreases, or
      remains constant with abstinence in humans. We investigated effects of abstinence
      on cue-induced craving in cigarette smokers. METHODS: Eighty-six non-treatment
      seeking, adult smokers (>=10 cigarettes daily) were paid to abstain for 7 (Group
      1), 14 (Group 2), or 35 (Groups 3 and 4) days. Abstinence was verified daily.
      Groups 1, 2, and 3 underwent a single cue session on the final abstinence day (7,
      14, or 35). Group 4 viewed cues on Days 7, 14, and 35. RESULTS: Between and
      within groups, smoking-cue-induced craving increased with abstinence on some
      measures. Cue-induced craving was greater in Group 3 (35-day) compared with Group
      1 (7-day). Within Group 4, cue-induced craving was greater at 35 than 14 days.
      Cue-induced craving did not decrease with abstinence on any measure. CONCLUSIONS:
      We present initial evidence of incubation of cue-induced craving in humans. The
      observation that cue-induced craving increases with abstinence, even as
      "background" craving and withdrawal symptoms subside, might have treatment
      implications.

PMID- 20817136
TI  - Spreading and retraction as a function of drop size.
AB  - We simulate the spreading and retraction of a two-dimensional drop over a thin
      film in the small slope limit for drop heights ranging from a few nanometers to
      hundreds of nanometers. Drop motion is initiated by an impulsive change in
      surface wettability expressed in terms of disjoining pressure. Owing to the
      presence of the film, these simulations require no closure condition at the
      'apparent' contact line. Rather, we study the relationships that emerge between
      the apparent contact line velocity and dynamic contact angles. The disjoining
      pressure that we study includes stabilizing van der Waals interactions and
      destabilizing acid-base interactions. Changes in wetting conditions that promote
      spreading place the thin film surrounding the drop out of equilibrium; the drop
      spreads as the film thickens to its new equilibrium value. Changes in wetting
      conditions that promote retraction can either place the thin film out of
      equilibrium in a stable regime, or they can place the thin film in a spinodally
      unstable regime. We study drop rearrangement as a function of drop scale for
      these three cases. Small drops, with heights on the same order as the film
      thickness, are strongly influenced by disjoining pressure gradients everywhere
      beneath them. Larger drops, with heights at least an order of magnitude greater
      than the film thickness, have disjoining pressure gradients isolated near the
      apparent contact line at all times. For these larger drops, after initial
      dynamics, macroscopic behavior is recovered; drops move in agreement with
      Tanner's law. However, dynamics associated with the thin film can play a leading
      role in the ensuing drop response even after Tanner's law emerges. In particular,
      when drops retract over spinodally unstable films, retraction occurs in three
      regimes. Rims form near the apparent contact line over time scales comparable to
      the time scale for the instability. The rim geometry can be characterized in
      terms of spinodal film thicknesses. The rims then propagate toward the bulk drop.
      Finally, the rim disappears and the drop assumes a cap-like shape. Tanner's law
      is obeyed during the latter two regimes. Attempts to simulate drop rearrangements
      disregarding the thin film dynamics before Tanner's law manifests can lead to
      erroneous outcomes, as shown in simulations of drop retraction on a solid surface
      with an imposed Navier slip length.

PMID- 20817137
TI  - Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome.
AB  - Sensenbrenner syndrome/cranioectodermal dysplasia (CED) is an autosomal-recessive
      disease that is characterized by craniosynostosis and ectodermal and skeletal
      abnormalities. We sequenced the exomes of two unrelated CED patients and
      identified compound heterozygous mutations in WDR35 as the cause of the disease
      in each of the two patients independently, showing that it is possible to find
      the causative gene by sequencing the exome of a single sporadic patient. With RT
      PCR, we demonstrate that a splice-site mutation in exon 2 of WDR35 alters
      splicing of RNA on the affected allele, introducing a premature stop codon. WDR35
      is homologous to TULP4 (from the Tubby superfamily) and has previously been
      characterized as an intraflagellar transport component, confirming that
      Sensenbrenner syndrome is a ciliary disorder.

PMID- 20817138
TI  - Mutability of Y-chromosomal microsatellites: rates, characteristics, molecular
      bases, and forensic implications.
AB  - Nonrecombining Y-chromosomal microsatellites (Y-STRs) are widely used to infer
      population histories, discover genealogical relationships, and identify males for
      criminal justice purposes. Although a key requirement for their application is
      reliable mutability knowledge, empirical data are only available for a small
      number of Y-STRs thus far. To rectify this, we analyzed a large number of 186 Y
      STR markers in nearly 2000 DNA-confirmed father-son pairs, covering an overall
      number of 352,999 meiotic transfers. Following confirmation by DNA sequence
      analysis, the retrieved mutation data were modeled via a Bayesian approach,
      resulting in mutation rates from 3.78 * 10(-4) (95% credible interval [CI], 1.38
      * 10(-5) - 2.02 * 10(-3)) to 7.44 * 10(-2) (95% CI, 6.51 * 10(-2) - 9.09 * 10(
      2)) per marker per generation. With the 924 mutations at 120 Y-STR markers, a
      nonsignificant excess of repeat losses versus gains (1.16:1), as well as a strong
      and significant excess of single-repeat versus multirepeat changes (25.23:1), was
      observed. Although the total repeat number influenced Y-STR locus mutability most
      strongly, repeat complexity, the length in base pairs of the repeated motif, and
      the father's age also contributed to Y-STR mutability. To exemplify how to
      practically utilize this knowledge, we analyzed the 13 most mutable Y-STRs in an
      independent sample set and empirically proved their suitability for
      distinguishing close and distantly related males. This finding is expected to
      revolutionize Y-chromosomal applications in forensic biology, from previous male
      lineage differentiation toward future male individual identification.

PMID- 20817139
TI  - BOOST: A fast approach to detecting gene-gene interactions in genome-wide case
      control studies.
AB  - Gene-gene interactions have long been recognized to be fundamentally important
      for understanding genetic causes of complex disease traits. At present,
      identifying gene-gene interactions from genome-wide case-control studies is
      computationally and methodologically challenging. In this paper, we introduce a
      simple but powerful method, named "BOolean Operation-based Screening and Testing"
      (BOOST). For the discovery of unknown gene-gene interactions that underlie
      complex diseases, BOOST allows examination of all pairwise interactions in genome
      wide case-control studies in a remarkably fast manner. We have carried out
      interaction analyses on seven data sets from the Wellcome Trust Case Control
      Consortium (WTCCC). Each analysis took less than 60 hr to completely evaluate all
      pairs of roughly 360,000 SNPs on a standard 3.0 GHz desktop with 4G memory
      running the Windows XP system. The interaction patterns identified from the type
      1 diabetes data set display significant difference from those identified from the
      rheumatoid arthritis data set, although both data sets share a very similar hit
      region in the WTCCC report. BOOST has also identified some disease-associated
      interactions between genes in the major histocompatibility complex region in the
      type 1 diabetes data set. We believe that our method can serve as a
      computationally and statistically useful tool in the coming era of large-scale
      interaction mapping in genome-wide case-control studies.

PMID- 20817140
TI  - Homo-C-nucleoside analogs III. Studies on the base-catalyzed dehydrative
      cyclization of 4-(d-manno-pentitol-1-yl)-2-phenyl-2H-1,2,3-triazole.
AB  - Treatment of 4-(d-manno-pentitol-1-yl)-2-phenyl-2H-1,2,3-triazole with one molar
      equivalent of 2,4,6-triisopropylbenzenesulfonyl chloride (TIBSCl) in pyridine
      solution afforded the homo-C-nucleoside analog; 4-(2,5-anhydro-d-manno-pentitol-1
      yl)-2-phenyl-2H-1,2,3-triazole in 54% yield and 4-(alpha-d-arabinopyranosyl)-2
      phenyl-2H1,2,3-triazole analog in 3% yield. The 4-(5-O
      triisopropylbenzenesulfonyl)-d-manno-pentitol-1-yl)-2-phenyl-2H-1,2,3-triazole
      analog was isolated as an intermediate and identified as its tetra-O-acetyl
      derivative. The 4-(5-chloro-5-deoxy-d-manno-pentitol-1-yl)-2-phenyl-2H-1,2,3
      triazole analog was isolated as a byproduct. The structure and anomeric
      configuration of the products were determined by acylation, NMR spectroscopy, and
      mass spectrometry.

PMID- 20817141
TI  - The molecular basis for sonographic cervical shortening at term: identification
      of differentially expressed genes and the epithelial-mesenchymal transition as a
      function of cervical length.
AB  - OBJECTIVE: The purpose of this study was to determine whether cervical shortening
      of a ripe cervix at term is associated with changes in the cervical
      transcriptome. STUDY DESIGN: Sonographically measured cervical lengths and biopsy
      specimens were obtained from 19 women at term who were not in labor with a ripe
      cervix. Affymetrix HG-U133 Plus 2.0 arrays (Affymetrix Inc, Santa Clara, CA) were
      used. Gene expression was analyzed as a function of cervical length. Gene
      Ontology, pathway analyses, quantitative real-time reverse transcription
      polymerase chain reaction, and immunohistochemistry were performed. RESULTS:
      Cervical length shortening was associated with differential expression of 687
      genes. Fifty-four biologic processes, 22 molecular functions, and 9 pathways were
      enriched. Quantitative real-time reverse transcription-polymerase chain reaction
      analysis confirmed differential expression of 13 genes. Bone morphogenetic
      protein-7, claudin-1, integrin beta-6, and endometrial progesterone-induced
      protein messenger RNA, and protein expressions were down-regulated with cervical
      shortening. CONCLUSION: Sonographic cervical shortening in patients at term who
      are not in labor with a ripe cervix is associated with changes in the uterine
      cervix transcriptome. The epithelial-mesenchymal transition may participate in
      the mechanism of cervical shortening at term.

PMID- 20817142
TI  - Role of KATP and L-type Ca2+ channel activities in regulation of ovine uterine
      vascular contractility: effect of pregnancy and chronic hypoxia.
AB  - OBJECTIVE: Our objective was to determine whether the pregnancy and high altitude
      long-term hypoxia-mediated changes in uterine artery contractility were regulated
      by K(ATP) and L-type Ca(2+) channel activities. STUDY DESIGN: Uterine arteries
      were isolated from nonpregnant and near-term pregnant ewes that had been
      maintained at sea level (~300 m) or exposed to high altitude (3801 m) for 110
      days. Isometric tension was measured in a tissue bath. RESULTS: Pregnancy
      increased diazoxide, but not verapamil-induced relaxations. Long-term hypoxia
      attenuated diazoxide-induced relaxations in near-term pregnant uterine arteries,
      but enhanced verapamil-induced relaxations in nonpregnant uterine arteries.
      Diazoxide decreased the maximal response (E(max)) of phenylephrine-induced
      contractions in near-term pregnant uterin arteries but not nonpregnant uterine
      arteries in normoxic sheep. In contrast, diazoxide had no effect on phenylephrine
      induced E(max) in near-term pregnant uterine arteries but decreased it in
      nonpregnant uterine arteries in long-term hypoxia animals. Verapamil decreased
      the E(max) and pD(2) (-logEC(50)) of phenylephrine-induced contractions in both
      nonpregnant uterine arteries and near-term pregnant uterine arteries in normoxic
      and long-term hypoxia animals, except nonpregnant uterine arteries of normoxic
      animals in which verapamil showed no effect on the pD(2). CONCLUSION: The results
      suggest that pregnancy selectively increases K(ATP), but not L-type Ca(2+)
      channel activity. Long-term hypoxia decreases the K(ATP) channel activity, which
      may contribute to the enhanced uterine vascular myogenic tone observed in
      pregnant sheep at high altitude hypoxia.

PMID- 20817143
TI  - Mental health and access to services among US women of reproductive age.
AB  - OBJECTIVE: The objective of the study was to estimate prevalence of depression
      and serious psychological distress (SPD) and mental health service receipt among
      reproductive-age women. STUDY DESIGN: We used 2006-2007 nationally representative
      data to estimate the prevalence of depression and SPD among nonpregnant women
      aged 18 to 44 years. Using logistic regression, we individually examined
      predictors of depression and SPD and characteristics associated with clinical
      diagnosis and current treatment. RESULTS: More than 14% of women had current
      depression and 2.7% had current SPD. Risk factors for major depression and SPD
      included older age, less education, being unmarried, inability to
      work/unemployed, and low income. Among depressed women, 18-24 year-olds, nonwhite
      women, those with children, the employed, and urban women had lower odds of
      clinical diagnosis. Among women with SPD, Hispanic, employed, and those without
      health insurance had lower odds of receiving treatment. CONCLUSION: Mental health
      conditions are prevalent among women of reproductive age and a substantial
      proportion goes untreated.

PMID- 20817144
TI  - Evaluation of a transvaginal mesh delivery system for the correction of pelvic
      organ prolapse: subjective and objective findings at least 1 year after surgery.
AB  - OBJECTIVE: We sought to track objective and subjective outcomes >=1 year after
      transvaginal mesh system to correct prolapse. STUDY DESIGN: This was a
      retrospective cohort study of 120 women who received a transvaginal mesh
      procedure (Avaulta Solo, CR Bard Inc, Covington, GA). Outcomes were pelvic organ
      prolapse quantification values; Pelvic Floor Distress Inventory, Short Form
      20/Pelvic Floor Impact Questionnaire, Short Form 7 scores; and a surgical
      satisfaction survey. "Surgical failure" was defined as pelvic organ prolapse
      quantification point >0, and/or any reports of vaginal bulge. RESULTS: Of 120
      patients, 116 (97%) were followed up for a mean of 14.4 months (range, 12-30). In
      all, 74 patients had only anterior mesh, 21 only posterior mesh, and 21 both
      meshes. Surgical cure rate was 81%. Surgical failure was more common if
      preoperative point C >=+2 (35% vs 16%; P = .04). Mesh erosion and de novo pain
      occurred in 11.7% and 3.3%, respectively. Pelvic Floor Distress Inventory, Short
      Form 20/Pelvic Floor Impact Questionnaire, Short Form 7 scores improved (P <
      .01). CONCLUSION: Objective and subjective improvements occurred at >=1 year, yet
      failure rates were high when preoperative point C was >=+2.

PMID- 20817145
TI  - Prevention of postoperative peritoneal adhesions: a review of the literature.
AB  - BACKGROUND: postoperative adhesions are a significant health problem with major
      implications on quality of life and health care expenses. The purpose of this
      review was to investigate the efficacy of preventative techniques and adhesion
      barriers and identify those patients who are most likely to benefit from these
      strategies. METHODS: the National Library of Medicine, Medline, Embase, and
      Cochrane databases were used to identify articles related to postoperative
      adhesions. RESULTS: ileal pouch-anal anastomosis, open colectomy, and open
      gynecologic procedures are associated with the highest risk of adhesive small
      bowel obstruction (class I evidence). Based on expert opinion (class III
      evidence) intraoperative preventative principles, such as meticulous hemostasis,
      avoiding excessive tissue dissection and ischemia, and reducing remaining
      surgical material have been published. Laparoscopic techniques, with the
      exception of appendicitis, result in fewer adhesions than open techniques (class
      I evidence). Available bioabsorbable barriers, such as hyaluronic
      acid/carboxymethylcellulose and icodextrin 4% solution, have been shown to reduce
      adhesions (class I evidence). CONCLUSIONS: postoperative adhesions are a
      significant health problem with major implications on quality of life and health
      care. General intraoperative preventative techniques, laparoscopic techniques,
      and the use of bioabsorbable mechanical barriers in the appropriate cases reduce
      the incidence and severity of peritoneal adhesions.

PMID- 20817146
TI  - Hypercalcitonemia revealing a somatostatinoma.
AB  - Somatostatinoma are rare well-differentiated endocrine tumors with malignant
      behavior arising from the pancreas and duodenum. They are defined by somatostatin
      positive immunostaining of the majority of tumor cells. The main clinical
      features are diabetes, diarrhea and biliary lithiasis related to somatostatin
      production. Somatostatinoma secreting both calcitonin and somatostatin may be
      unrecognized as a small number of such observations have been published. We
      report the case of a 57- year-old woman referred for weight loss, diarrhea and
      worsening diabetes. Computer tomography scan revealed multiple hypervascular
      liver lesions suggestive of metastases. High plasma calcitonin level was
      evidenced, with normal chromogranin-A value, and high plasma somatostatin results
      lately communicated. Calcitonin secretion of extra-thyroidal origin was suspected
      leading to the identification of a pancreatic mass by further multiphase CT. The
      patient underwent left pancreatectomy with surgical hepatic resection.
      Histological and immunostaining studies confirmed definitive diagnosis of
      somatostatinoma secreting both somatostatin and calcitonin. Plasma calcitonin
      should be measured in the assessment of duodeno-pancreatic endocrine neoplasm.
      Calcitonin determination is available, more reproducible than other specific
      pancreatic endocrine markers and could be effective for diagnosis and follow-up
      of such foregut-derived endocrine neoplasia.

PMID- 20817147
TI  - Increased annual frequency of Hashimoto's thyroiditis between years 1988 and 2007
      at a cytological unit of Sicily.
AB  - Like other auto-immune diseases, Hashimoto's thyroiditis (HT) results from the
      interaction of genetic with environmental factors. Only few studies have
      evaluated the year-to-year change in frequency of HT over a wide period of time.
      The endocrine division of our Hospital has reported a great increase in the
      annual frequency of HT between 1975 and 2005, and a progressive decrease in both
      age at presentation and female to male (F/M) ratio starting in the mid-1990s.
      Between years 1988 and 2007, we have collected 8397 adequate examinations by fine
      needle aspiration cytology (FNAC) on 8397 persons referred for the evaluation of
      a solitary or dominant thyroid nodule (total FNAC and persons=8520) with a 14
      fold increase in 2007 over 1988. In this 20-year period, cases of HT, De
      Quervain's thyroiditis (DQT) and Riedel's thyroiditis (RT) were 490, 36 and two,
      respectively. HT cases were one in 1988 but 90 in 2007, with a significant upward
      temporal trend (r=0.919, P<0.001) and significant downward trend for age at FNAC
      (r=-0.466, P<0.05). In contrast, DQT cases were zero and one, respectively, with
      no significant temporal trend (r=0.29, P=0.21). The HT increase in frequency
      started in 1996 (+350% over 1995). Until 1995 there was only one man, but there
      were 22 men in 2005-2007. These FNAC data provide independent confirmation to the
      data from the endocrine division of the same hospital, further supporting the
      conclusion that only environmental modifications can explain these marked changes
      that have occurred in such a relatively short period of time.

PMID- 20817148
TI  - Group person-based cognitive therapy for distressing voices: Pilot data from nine
      groups.
AB  - The present study examines the impact of group Person-Based Cognitive Therapy
      (PBCT) for distressing voices within an uncontrolled evaluation. In particular it
      utilizes a framework of acceptance of voices and self to enhance well-being and
      reduce distress and perceived voice-control. Sixty-two participants entered one
      of nine PBCT groups conducted over 8-12 sessions. Fifty participants completed
      therapy. Measures of well-being, distress, control and relating characteristics
      were completed pre- and post-therapy and at brief follow-up. Data were subjected
      to an intention-to-treat analysis. The groups achieved significant benefits in
      terms of well-being, distress, control and dependence upon the voice. The present
      study is the first to report significant improvement in both distress and
      control. Consequently, Group PBCT for distressing voices may prove a useful
      addition to existing psychological interventions and is worthy of further
      investigation. The findings are discussed in relation to clinical implications
      and limitations.

PMID- 20817149
TI  - Distinguishing intentions from desires: contributions of the frontal and parietal
      lobes.
AB  - The ability to represent desires and intentions as two distinct mental states was
      investigated in patients with parietal (N=8) and frontal (N=6) lesions and in age
      matched controls (N=7). A task was used where the satisfaction of the desire and
      the fulfilment of the intention did not co-vary and were manipulated in a 2 * 2
      set. In two experiments we show that lesions to the frontal lobe may impair the
      ability to deal with desires when their outcome is not congruent with that of the
      intention, and that parietal damage - especially if it encompasses the left
      temporo-parietal junction - may cause severe difficulties in the processing of
      both desires and intentions. The implications of the results for the
      neuropsychological and the developmental literature are discussed.

PMID- 20817150
TI  - Power, rights, respect and data ownership in academic research with indigenous
      peoples.

PMID- 20817152
TI  - Procedural learning in schizophrenia: reconciling the discrepant findings.
AB  - BACKGROUND: Studies of procedural learning in schizophrenia have been
      inconsistent, sometimes finding it to be preserved and sometimes impaired. This
      study examined three factors that could account for the variability among
      findings: type of task, presence of general intellectual impairment, and the
      extrapyramidal side effects of neuroleptic treatment. METHODS: Forty-three
      patients with schizophrenia and 22 normal control subjects were examined with
      three different paradigms: the pursuit rotor, mirror reading, and probabilistic
      learning ("weather prediction"). A subgroup of intellectually preserved patients
      was also examined. Patients with and without tardive dyskinesia and with and
      without Parkinsonism were also compared. RESULTS: The schizophrenic patients
      showed learning comparable to the control subjects on the pursuit rotor and
      mirror reading but were impaired on the probabilistic learning task. However,
      this last difference disappeared when the subgroup of intellectually preserved
      patients was compared with a subgroup of matched control subjects. Patients with
      and without tardive dyskinesia or Parkinsonism showed similar learning on all
      three tasks, but patients with tardive dyskinesia showed poorer overall
      performance than those without. CONCLUSIONS: Procedural learning tends to be
      preserved in schizophrenia, and when impairment is found, differences in the
      overall level of intellectual function might be the determining factor.

PMID- 20817151
TI  - Oxidative stress and amyloid-beta pathology in normal individuals with a maternal
      history of Alzheimer's.
AB  - BACKGROUND: Epidemiology and imaging studies showed that cognitively normal (NL)
      individuals with a maternal history (MH) of late-onset Alzheimer's disease (LOAD)
      might be at increased risk for Alzheimer's disease (AD) compared with NL with a
      paternal history (PH) and NL with a negative family history of LOAD (NH). With a
      panel of cerebrospinal fluid (CSF) markers, this study examined whether NL MH
      showed evidence for AD pathology compared with PH and NH. METHODS: Fifty-nine 40
      80-year-old NL subjects were examined, including 23 MH and 14 PH whose parents
      had a clinician-certified diagnosis of LOAD and 22 NH. All subjects completed
      clinical neuropsychological examinations and a lumbar puncture to measure CSF
      levels of amyloid-beta (Abeta(40), Abeta(42), Abeta(42/40)), total and
      hyperphosphorylated tau (T-Tau and P-Tau(231); markers of axonal degeneration and
      neurofibrillary tangles, respectively), and F2-isoprostanes (IsoP) (a marker of
      oxidative stress). RESULTS: Groups were comparable for demographic and
      neuropsychological measures. The MH subjects showed higher IsoP and reduced
      Abeta(42/40) CSF levels compared with NH and with PH (p values <= .05), whereas
      no differences were found between NH and PH. No group differences were found for
      P-Tau(231) and T-Tau. The IsoP and Abeta(42/40) levels were correlated only
      within the MH group (R2 = .32, p = .005) and discriminated MH from the other
      subjects with 70% accuracy (relative risk = 3.7%, 95% confidence interval = 1.6
      9.7, p < .001). Results remained significant controlling for age, gender,
      education, and apolipoprotein E genotype. CONCLUSIONS: Adult children of LOAD
      affected mothers express a pathobiological phenotype characterized by Abeta
      associated oxidative stress consistent with AD, which might reflect increased
      risk for developing the disease.

PMID- 20817153
TI  - A preliminary study of D-cycloserine augmentation of cognitive-behavioral therapy
      in pediatric obsessive-compulsive disorder.
AB  - BACKGROUND: Research on the neural circuitry underlying fear extinction has led
      to the examination of D-cycloserine (DCS), a partial agonist at the N-methyl-D
      aspartate receptor in the amygdala, as a method to enhance exposure therapy
      outcome. Preliminary results have supported the use of DCS to augment exposure
      therapy in adult anxiety disorders; however, no data have been reported in any
      childhood anxiety disorder. Thus, we sought to preliminarily examine whether
      weight-adjusted DCS doses (25 or 50 mg) enhanced the overall efficacy of
      cognitive-behavioral therapy (CBT) for pediatric obsessive-compulsive disorder
      (OCD). METHOD: Participants were 30 youth (aged 8-17) with a primary diagnosis of
      OCD. The study design was a randomized, double-blinded, placebo-controlled
      augmentation trial examining CBT + DCS versus CBT + Placebo (15 youth per group).
      All patients received seven exposure and response prevention sessions paired with
      DCS or placebo taken 1 hour before sessions. RESULTS: Although not significantly
      different, compared with the CBT + Placebo group, youth in the CBT + DCS arm
      showed small-to-moderate treatment effects (d = .31-.47 on primary outcomes). No
      adverse events were recorded. CONCLUSIONS: These results complement findings in
      adult OCD and non-OCD anxiety disorders and provide initial support for a more
      extensive study of DCS augmentation of CBT among youth with OCD.

PMID- 20817154
TI  - Preparation and antimicrobial activity of scleraldehyde from Schizophyllum
      commune.
AB  - The present study investigates the antimicrobial activity of oxidized
      schizophyllan (scleraldehyde) against Gram-positive and Gram-negative bacteria by
      diffusion and tube dilution analysis. Schizophyllan is a natural polysaccharide
      produced by fungi of the genus Schizophyllum. Periodate oxidation specifically
      cleaves the vicinal glycols in scleraldehyde to form their dialdehyde
      derivatives. The antibacterial activity exhibited by scleraldehyde was defined
      using various tests such as the disc diffusion assay, minimum inhibitory
      concentration (MIC) and minimum bactericidal concentration (MBC). MIC and MBC
      values were found to be in the range of 3.0-8.0 mg/mL. Hence, the present studies
      establish that the scleraldehyde possesses effective antibacterial properties and
      can be used as a biopreservative for preservation of raw hides and skins.

PMID- 20817155
TI  - Bromodimethylsulfonium bromide (BDMS) mediated dithioacetalization of
      carbohydrates under solvent-free conditions.
AB  - A variety of diethyl dithioacetals of sugars can be prepared in very good yields
      by the reaction of various monosaccharides with ethanethiol in the presence of 3
      mol% bromodimethylsulfonium bromide (BDMS) at 0-5 degrees C. Similarly, dipropyl
      dithioacetal derivatives can also be obtained in good yields using propanethiol
      under identical reaction conditions. These dithioacetal derivatives were
      characterized by per-O-acetylation using silica gel-supported perchloric acid.
      The significant features of the present protocol are good-to-excellent yields,
      mild, clean, and solvent-free reaction conditions. This method is extremely
      suitable for the large-scale preparation of dithioacetal derivatives of various
      sugars.

PMID- 20817156
TI  - On the stereoselectivity of glycosidation of thiocyanates, thioimidates, and
      thioglycosides.
AB  - Comparative side-by-side glycosylation studies demonstrated that glycosyl
      thiocyanates, thioimidates, and thioglycosides provide comparative
      stereoselectivities in glycosylations. Very high alpha-stereoselectivity that was
      previously recorded for glycosyl thiocyanates can be achieved, but only if
      glycosyl acceptors are equipped with electron-withdrawing acyl substituents.
      Partially benzylated glycosyl acceptors provided relatively modest
      stereoselectivity, which was on a par with other common glycosyl donors.
      Accordingly, thioimidates and thioglycosides showed high stereoselectivity
      similarly to that of thiocyanates with different classes of acylated primary and
      secondary glycosyl acceptors.

PMID- 20817157
TI  - Bronchobiliary fistula: a rare complication of hepatic endometriosis.
AB  - OBJECTIVE: To report the case and surgical therapy of a patient with bilioptysis
      after vaginal delivery, caused by bronchobiliary fistula. Histologic analysis
      revealed endometrial glands embedded in the decidual stroma neighboring the liver
      and the lung. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 39
      year-old patient, 7 days after vaginal delivery, without endometrial history.
      INTERVENTION(S): Synchronous liver and lung resection of a bronchobiliary fistula
      by laparotomy and a transdiaphragmatic approach. MAIN OUTCOME MEASURE(S): For
      complicated brochobiliary fistula caused by endometriosis, radical surgical
      treatment is mandatory. RESULT(S): Histopathologic analyses confirmed the
      presence of clusters of endometrial glands embedded in the decidual stroma that
      were neighboring the liver, and perifistulous lung tissue was shown to contain
      biliary pigment absorbed by macrophages and their derivatives. CONCLUSION(S):
      Hepatic and perihepatic endometriosis can cause a bronchobiliary fistula.
      Exacerbation of the symptoms can be triggered by high estrogen levels,
      physiologically dominating the last trimester. For such a rare case, surgery is
      mandatory.

PMID- 20817158
TI  - Executive function is necessary for perspective selection, not Level-1 visual
      perspective calculation: evidence from a dual-task study of adults.
AB  - Previous research suggests that perspective-taking and other "theory of mind"
      processes may be cognitively demanding for adult participants, and may be
      disrupted by concurrent performance of a secondary task. In the current study, a
      Level-1 visual perspective task was administered to 32 adults using a dual-task
      paradigm in which the secondary task tapped executive function. Results suggested
      that the secondary task did not affect the calculation of perspective, but did
      affect the selection of the relevant (Self or Other) perspective for a given
      trial. This is the first direct evidence of a cognitively efficient process for
      "theory of mind" in adults that operates independently of executive function. The
      contrast between this and previous findings points to a distinction between
      simple perspective-taking and the more complex and cognitively demanding
      abilities more typically examined in studies of "theory of mind". It is suggested
      that these findings may provide a parsimonious explanation of the success of
      infants on 'indirect' measures of perspective-taking that do not explicitly
      require selection of the relevant perspective.

PMID- 20817159
TI  - Exploring the roles of the executive and short-term feature-binding functions in
      retrieval of retrograde autobiographical memories in severe traumatic brain
      injury.
AB  - Conway's autobiographical memory (AM) model postulates that memories are not
      stored in a crystallised form in long-term memory but are reconstructed at time
      of retrieval via executive and binding processes, to create a temporary
      multimodal representation from different AM knowledge. Traumatic brain injury
      (TBI) impairs AM recollection. However, no study has yet considered the distinct
      roles of executive and short-term feature-binding functions in the retrieval
      deficits of retrograde AMs after TBI. Examining a group of 33 TBI patients and 33
      controls, our study addresses these roles through a first-ever exploration of the
      links between performance on an AM verbal fluency evaluation that distinguishes
      four levels of representation, from semantic to episodic (lifetime periods,
      general events, specific events, specific details of a specific event), and three
      executive functions (shifting, inhibition and updating) and two short-term
      feature-binding functions (short-term formation and maintenance of multimodal
      representations). The results showed that TBI patients were impaired compared to
      controls in the retrieval of both semantic and episodic retrograde AM
      representations, but especially for the most episodic level of AM, in the three
      executive functions and the short-term maintenance of multimodal representations.
      Regression analyses indicated that the executive predictors (mainly updating)
      mediated a large proportion (over 70%) of TBI-related deficit on the retrieval of
      lifetime periods, general events and specific events, in contrast with the main
      impairment on generation of specific details which were only mildly (just 12%)
      predicted by the short-term maintenance of multimodal representations. Additional
      analyses in a subgroup of patients point to episodic memory abilities and time
      since injury in predicting the retrieval of specific events and details. In
      summary, the present study mainly emphasizes that the executive deficits in TBI
      are involved in the disruption of the first levels of AM generative processes
      that give access to the multiple episodic details recollection.

PMID- 20817160
TI  - Learning control for batch thermal sterilization of canned foods.
AB  - A control technique based on Reinforcement Learning is proposed for the thermal
      sterilization of canned foods. The proposed controller has the objective of
      ensuring a given degree of sterilization during Heating (by providing a minimum
      temperature inside the cans during a given time) and then a smooth Cooling,
      avoiding sudden pressure variations. For this, three automatic control valves are
      manipulated by the controller: a valve that regulates the admission of steam
      during Heating, and a valve that regulate the admission of air, together with a
      bleeder valve, during Cooling. As dynamical models of this kind of processes are
      too complex and involve many uncertainties, controllers based on learning are
      proposed. Thus, based on the control objectives and the constraints on input and
      output variables, the proposed controllers learn the most adequate control
      actions by looking up a certain matrix that contains the state-action mapping,
      starting from a preselected state-action space. This state-action matrix is
      constantly updated based on the performance obtained with the applied control
      actions. Experimental results at laboratory scale show the advantages of the
      proposed technique for this kind of processes.

PMID- 20817161
TI  - Paid work, domestic work, and other determinants of pregnancy outcome in Ibadan,
      southwest Nigeria.
AB  - OBJECTIVE: To identify the determinants of low birth weight (LBW), preterm birth,
      and stillbirth, and the factors associated with paid or domestic work that
      affected pregnancy outcome in Ibadan, Nigeria. METHODS: A cross-sectional study
      of women who delivered live or stillborn singleton neonates at 4 hospitals
      between February and June 2008. Participants were interviewed to obtain
      information on paid and domestic work activities during pregnancy, as well as
      obstetric history. Pregnancy outcomes and other clinical data were extracted from
      case notes. RESULTS: A total of 1504 mothers aged 20-45 years recorded 137 (9.1%)
      LBW neonates (<2.5 kg), 154 (10.2%) preterm deliveries (<37 weeks), and 56 (3.7%)
      stillbirths. There was no overall increased risk of these outcomes among working
      mothers. Multivariate logistic regression analysis of working mothers who had
      booked their deliveries revealed that lifting heavy objects at home, a clinical
      record of proteinuria, and hospital admission during pregnancy were associated
      with LBW. Predictors for preterm birth were self-reported exposure to vibration
      at work, nulliparity, history of preterm birth, 4 or fewer compared with more
      than 8 antenatal visits, and prolonged rupture of membranes. Predictors for
      stillbirth were low education and prolonged rupture of membranes. CONCLUSION: The
      results further support recommendations that physical exertion in paid and
      domestic work should be reduced during pregnancy.

PMID- 20817163
TI  - Simulated elliptical bioprosthetic valve deformation: implications for asymmetric
      transcatheter valve deployment.
AB  - The asymmetric, elliptical shape of a transcatheter aortic valve (TAV), after
      implantation into a calcified aortic root, has been clinically observed. However,
      the impact of elliptical TAV configuration on TAV leaflet stress and strain
      distribution and valve regurgitation is largely unknown. In this study, we
      developed computational models of elliptical TAVs based on a thin pericardial
      bioprosthetic valve model recently developed. Finite element and computational
      fluid dynamics simulations were performed to investigate TAV leaflet structural
      deformation and central backflow leakage, and compared with those of a nominal
      symmetric TAV. From the results, we found that for a distorted TAV with an
      elliptical eccentricity of 0.68, the peak stress increased significantly by 143%
      compared with the nominal circular TAV. When the eccentricity of an elliptical
      TAV was larger than 0.5, a central backflow leakage was likely to occur. Also,
      deployment of a TAV with a major calcified region perpendicular to leaflet
      coaptation line was likely to cause a larger valve leakage. In conclusion, the
      computational models of elliptical TAVs developed in this study could improve our
      understanding of the biomechanics involved in a TAV with an elliptical
      configuration and facilitate optimal design of next-generation TAV devices.

PMID- 20817162
TI  - Mechanisms of initial endplate failure in the human vertebral body.
AB  - Endplate failure occurs frequently in osteoporotic vertebral fractures and may be
      related to the development of high tensile strain. To determine whether the
      highest tensile strains in the vertebra occur in the endplates, and whether such
      high tensile strains are associated with the material behavior of the
      intervertebral disc, we used micro-CT-based finite element analysis to assess
      tissue-level strains in 22 elderly human vertebrae (81.5 +/- 9.6 years) that were
      compressed through simulated intervertebral discs. In each vertebra, we compared
      the highest tensile and compressive strains across the different compartments:
      endplates, cortical shell, and trabecular bone. The influence of Poisson-type
      expansion of the disc on the results was determined by compressing the vertebrae
      a second time in which we suppressed the Poisson expansion. We found that the
      highest tensile strains occurred within the endplates whereas the highest
      compressive strains occurred within the trabecular bone. The ratio of strain to
      assumed tissue-level yield strain was the highest for the endplates, indicating
      that the endplates had the greatest risk of initial failure. Suppressing the
      Poisson expansion of the disc decreased the amount of highly tensile-strained
      tissue in the endplates by 79.4 +/- 11.3%. These results indicate that the
      endplates are at the greatest risk of initial failure due to the development of
      high tensile strains, and that such high tensile strains are associated with the
      Poisson expansion of the disc. We conclude that initial failure of the vertebra
      is associated with high tensile strains in the endplates, which in turn are
      influenced by the material behavior of the disc.

PMID- 20817164
TI  - Structural and functional changes of the articular surface in a post-traumatic
      model of early osteoarthritis measured by atomic force microscopy.
AB  - The functional integrity of the articulating cartilage surface is a critical
      determinant of joint health. Although a variety of techniques exist to
      characterize the structural changes in the tissue with osteoarthritis (OA), some
      with extremely high resolution, most lack the ability to detect and monitor the
      functional changes that accompany the structural deterioration of this essential
      bearing surface. Atomic force microscopy (AFM) enables the acquisition of both
      structural and mechanical properties of the articular cartilage surface, with up
      to nanoscale resolution, making it particularly useful for evaluating the
      functional behavior of the macromolecular network forming the cartilage surface,
      which disintegrates in OA. In the present study, AFM was applied to the articular
      cartilage surfaces from six pairs of canine knee joints with post-traumatic OA.
      Microstructure (RMS roughness) and micromechanics (dynamic indentation modulus,
      E* of medial femoral condyle cartilages were compared between contralateral
      controls and cruciate-transected knee joints, which develop early signs of OA by
      three months after surgery. Results reveal a significant increase in RMS
      roughness and a significant four-fold decrease in E* in cartilages from cruciate
      transected joints versus contralateral controls. Compared to previous reports of
      changes in bulk mechanics, AFM was considerably more sensitive at detecting early
      cartilage changes due to cruciate-deficiency. The use of AFM in this study
      provides important new information on early changes in the natural history of OA
      because of its ability to sensitively detect and measure local structural and
      functional changes of the articular cartilage surface, the presumptive site of
      osteoarthritic initiation.

PMID- 20817165
TI  - Comparative study of the flavonoids of some Verbena species cultivated in Egypt
      by using high-performance liquid chromatography coupled with ultraviolet
      spectroscopy and atmospheric pressure chemical ionization mass spectrometry.
AB  - Verbena rigida L., Verbena tenera Spreng. and Verbena venosa L. were investigated
      for their flavonoid content. Analysis was carried out by high-performance liquid
      chromatography coupled to diode array UV detection (LC-UV), using different
      techniques, also using post-column addition of shift reagents, afforded precise
      structural information about the position of the free hydroxyl groups in the
      flavonoid nucleus. LC-MS using atmospheric pressure chemical ionization (APCI) in
      the positive mode provided the molecular weight, the number of hydroxyl groups,
      the number of sugars and an idea about the substitution pattern of the flavonoid.
      On-line UV and MS data demonstrated the presence of orientin, vitexin,
      isovitexin, luteolin, luteolin 7-O-glucoside, apigenin 7-O-glucoside in addition
      to luteolin, chryseriol and apigenin aglycones in the three Verbena species with
      different concentrations. Quantitative determination of flavonoid content
      revealed the presence of 69.84 mg/g dry sample, 88.26 mg/g dry sample and 85.82
      mg/g dry sample total flavonoid compounds in V. rigida L., V. tenera Spreng. and
      V. venosa L., respectively. The method developed for identification is useful for
      further chromatographic fingerprinting of plant flavonoids.

PMID- 20817166
TI  - Matrix solid-phase dispersion on column clean-up/pre-concentration as a novel
      approach for fast isolation of abuse drugs from human hair.
AB  - A simple and fast sample pre-treatment method based on matrix solid-phase
      dispersion (MSPD) for isolating cocaine, benzoylecgonine (BZE), codeine, morphine
      and 6-monoacethylmorphine (6-MAM) from human hair has been developed. The MSPD
      approach consisted of using alumina (1.80 g) as a dispersing agent and 0.6M
      hydrochloric acid (4 mL) as an extracting solvent. For a fixed hair sample mass
      of 0.050 g, the alumina mass to sample mass ratio obtained was 36. A previously
      conditioned Oasis HLB cartridge (2 mL methanol, plus 2 mL ultrapure water, plus 1
      mL of 0.2M/0.2M sodium hydroxide/boric acid buffer solution at pH 9.2) was
      attached to the end of the MSPD syringe for on column clean-up of the
      hydrochloric acid extract and for transferring the target compounds to a suitable
      solvent for gas chromatography (GC) analysis. Therefore, the adsorbed analytes
      were directly eluted from the Oasis HLB cartridges with 2 mL of 2% acetic acid in
      methanol before concentration by N(2) stream evaporation and dry extract
      derivatization with N-methyl-tert-butylsilyltrifluoroacetamide (BSTFA) and
      chlorotrimethylsilane (TMCS). The optimization/evaluation of all the factors
      affecting the MSPD and on column clean-up procedures has led to a fast sample
      treatment, and analytes extraction and pre-concentration can be finished in
      approximately 30 min. The developed method has been applied to eight hair samples
      from poli-drug abusers and measured analyte concentrations have been found to be
      statistically similar (95% confidence interval) to those obtained after a
      conventional enzymatic hydrolysis method (Pronase E).

PMID- 20817167
TI  - Hierarchical synthesis of silver nanoparticles and wires by copolymer templates
      and visible light.
AB  - Self-assembled silver wires in micro-meter scale were obtained from aqueous
      silver nitrate solution in the presence of a comb-like copolymer as the sole
      organic component. The requisite copolymer was easily prepared by the grafting
      poly(oxyethylene)-monoamine (POE-amine) onto poly(styrene-co-maleic anhydride)
      (SMA). Upon storage at ambient temperature with exposure to daylight, the aqueous
      AgNO(3)/SMA-POE solution gradually underwent a color changed from transparent
      pale-yellow to dark-violet over a period of hours, and after several months a
      solid precipitate was deposited. The formation process was monitored by
      ultraviolet-visible spectrometer, particle size analysis, scanning electron
      microscope, and transmission electron microscope. Silver wires were
      hierarchically formed by progressive transformation from the initial appearance
      of silver nanoparticles (ca. 10nm in diameter), followed by the intermediate
      rectangles (0.6-1.0MUm in width and 0.4MUm in length) in solution and ultimately
      the precipitates in micro-scale of silver wires at 1.6-6.4MUm in diameter and 100
      370MUm in length. The progressive formation of the precipitated silver wires was
      accelerated by the exposure of visible light as a photo-reducing energy source.
      The micron-scale wires have a silver content over 97.4wt.% and a sheet resistance
      of 5.5*10(1)Omega/square.

PMID- 20817168
TI  - Supporting children's counterfactual thinking with alternative modes of
      responding.
AB  - To speculate about counterfactual worlds, children need to ignore what they know
      to be true about the real world. Prior studies yielding individual differences
      data suggested that counterfactual thinking may be related to overcoming
      prepotent responses. In two experiments, we manipulated how 3- to 5-year-olds
      responded to counterfactual conditional and syllogism tasks. In Experiment 1
      (N=39), children's performance improved on both conditional and syllogism tasks
      when they responded with an arrow rather than pointing with a finger. In
      Experiment 2 (N=42), 3- and 4-year-olds benefited from both an arrow manipulation
      and, separately, the introduction of a delay before responding. We suggest that
      both manipulations help children to overcome an impulsive prepotent response to
      counterfactual questions arising from a default assumption that information about
      the past is true.

PMID- 20817169
TI  - A mutant single nucleotide polymorphism of follicle-stimulating hormone receptor
      is associated with a lower risk of endometriosis.
AB  - Six hundred thirty-seven Taiwanese Chinese women including 300 patients with
      endometriosis and 337 controls without endometriosis were enrolled to investigate
      the association between nonsynonymous single nucleotide polymorphism of the FSH
      receptor gene and the risk of endometriosis. For the A/G polymorphism of FSH
      receptor gene (Asn680Ser), a univariate analysis for women with endometriosis
      demonstrated that both the GG genotype (680Ser/Ser) and GA genotype (680Ser/Asn)
      were associated with a significantly lower risk of endometriosis.

PMID- 20817170
TI  - Improving posttransplantation survival of human ovarian tissue by treating the
      host and graft.
AB  - OBJECTIVE: To improve posttransplantation survival of frozen-thawed human ovarian
      tissue in immunodeficient mice. DESIGN: Histologic study of transplanted human
      ovaries after treating the host and graft. SETTING: Infertility unit, university
      affiliated tertiary medical center. PATIENT(S): Ovarian tissue from six
      girls/women (aged 5-23 years) who had undergone ovarian laparoscopy for fertility
      preservation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Thawed ovarian
      samples were transplanted into the back muscle of immunodeficient mice divided
      into four groups: A) no treatment; B) host treatment with vitamin E and
      gonadotropins before and after grafting; C) graft incubation with vascular
      endothelial growth factor A (VEGF-A) and vitamin E before transplantation; and D)
      host as in B, graft as in C. Ungrafted thawed samples served as control.
      Assessment of graft survival was conducted by follicle counts, apoptosis
      evaluation, immunohistochemical stainings for proliferating cell nuclear antigen
      (PCNA) and VEGF-A expression. RESULT(S): Only grafts incubated before
      transplantation (groups C and D) retained their original size. Follicle number
      was low in all grafts. PCNA expression was found in most grafts. Apoptosis was
      significantly lower in the untreated and treated grafts transplanted into treated
      hosts (groups B and D) than in ungrafted-thawed samples and group A grafts. All
      grafted groups had significantly higher expression of VEGF-A than ungrafted
      thawed samples. CONCLUSION(S): Survival of transplanted human ovarian tissue may
      be improved by treatment of the host and graft. Further studies to evaluate
      treatments with a potential benefit in human ovarian autotransplantation are
      needed.

PMID- 20817172
TI  - Adolescent parents of critically ill newborns: rights and obligations.

PMID- 20817171
TI  - Celiac autoimmunity in children with type 1 diabetes: a two-year follow-up.
AB  - OBJECTIVE: To determine the benefits of screening for celiac autoimmunity via
      immunoglobulin A transglutaminase autoantibodies (TG) in children with type 1
      diabetes (T1D). STUDY DESIGN: We followed up 79 screening-identified TG+ and 56
      matched TG- children with T1D for 2 years to evaluate growth, bone mineral
      density, nutritional status, and diabetes control. TG+ subjects self-selected to
      gluten-free or gluten-containing diet. RESULTS: Of the initial cohort, 80% were
      available for reexamination after 2 years. TG+ subjects had consistently lower
      weight z-scores and higher urine N-telopeptides than TG- subjects, but similar
      measures of bone density and diabetes outcomes. TG+ children who remained on a
      gluten-containing diet had lower insulin-like growth factor binding protein 3 z
      scores compared with TG+ subjects who reported following a gluten-free diet.
      Children who continued with high TG index throughout the study had lower bone
      mineral density z-scores, ferritin, and vitamin D 25OH levels, compared with the
      TG- group. CONCLUSIONS: No significant adverse outcomes were identified in
      children with T1D with screening-identified TG+ who delay therapy with a gluten
      free diet for 2 years. Children with persistently high levels of TG may be at
      greater risk. The optimal timing of screening and treatment for celiac disease in
      children with T1D requires further investigation.

PMID- 20817173
TI  - Pyogenic diskitis of the L5-S1 disk space following inadvertent placement of a
      sacrocolpopexy screw.

PMID- 20817174
TI  - Uterine cervical diverticulum containing a blood clot.

PMID- 20817175
TI  - Seven cases of fetal ovarian cysts.

PMID- 20817176
TI  - Prenatal anxiety associated with male child preference among expectant mothers at
      10-20 weeks of pregnancy in Xiangyun County, China.
AB  - OBJECTIVE: To examine the relationship between male child preference and maternal
      prenatal psychological distress among expectant mothers from Xiangyun County,
      Yunnan Province, China. METHODS: Child gender preference, state-trait anxiety and
      depression, relationships with the husband and mother-in-law, and self-esteem
      were measured in a sample of 198 women between 10 and 20 weeks of pregnancy.
      Multivariate logistic regression analysis was used to identify risk factors for
      prenatal anxiety. RESULTS: Prenatal anxiety was correlated with male child
      preference (r=0.15, P<0.05), maternal age (r=-0.17, P<0.05), level of education
      (r=-0.23, P<0.01), self-esteem (r=-0.36, P<0.01), relationship with mother-in-law
      (r=-0.34, P<0.01), and relationship with husband (r=-0.35, P<0.01). Significant
      relationships were maintained in multivariate analysis that included gender
      preference, maternal education, pregnancy anxiety, self-esteem, number of people
      in the household, and relationship with husband as predictors (adjusted
      r(2)=0.28, P<0.001). CONCLUSION: Male child preference was associated with
      prenatal anxiety in this sample. Younger maternal age, lower self-esteem, lower
      level of education, worse relationship with husband, and less family cohesiveness
      were also related to prenatal anxiety. Expectant mothers experienced prenatal
      anxiety when there was strong family preference for sons.

PMID- 20817177
TI  - Risk factors for perinatal mortality in a Tunisian population.

PMID- 20817178
TI  - Treatment of high-grade squamous intraepithelial lesions in an area of Thailand
      with a high incidence of cervical cancer.
AB  - OBJECTIVE: To audit the treatment of high-grade squamous intraepithelial lesions
      (HSILs) at Chiang Mai University Hospital based on 12 standard requirements of
      the National Health Service Cervical Screening Programme. METHODS: Records were
      reviewed of all women with histologically proven HSIL undergoing treatment at
      Chiang Mai University Hospital between January 2005 and May 2009. RESULTS: Four
      of the standard requirements were not met: not all women underwent colposcopy
      before definitive treatment; the rate of specimen fragmentation was high; among
      women with ectocervical lesions, the rate of tissue removal to a depth of greater
      than 7 mm was low; and among women aged over 50 years with endocervical-margin
      involvement, the rate of repeat excision was low. CONCLUSION: This audit
      highlights four treatment practices that do not meet standard requirements and
      require detailed exploration. The development of guidelines for the treatment of
      cervical precancerous lesions in Thailand is challenging and merits further
      attention.

PMID- 20817179
TI  - Clinical significance of obstructive defecatory symptoms in women with pelvic
      organ prolapse.
AB  - OBJECTIVE: To determine whether the presence of obstructive defecatory symptoms
      is associated with the site and severity of pelvic organ prolapse. METHODS: A
      cross-sectional study was performed of women with pelvic organ prolapse of grade
      2 or greater who had completed a validated questionnaire that surveyed pelvic
      floor symptoms. Associations between patient characteristics, site and severity
      of prolapse, and obstructive bowel symptoms were investigated. RESULTS: Among 260
      women with pelvic organ prolapse, women with posterior vaginal wall prolapse were
      more likely to report obstructive symptoms, such as incomplete emptying (41% vs
      21%, P=0.003), straining at defecation (39% vs 19%, P=0.002), and splinting with
      defecation (36% vs 14%, P<0.001) compared with women without posterior vaginal
      wall prolapse. There was no significant association between any bowel symptom and
      increasing severity of prolapse. CONCLUSIONS: Obstructive bowel symptoms are
      significantly associated with the presence of posterior vaginal wall prolapse,
      but not with the severity of prolapse.

PMID- 20817180
TI  - Cerebrovascular disease incidence in central Spain (NEDICES): a population-based
      prospective study.
AB  - BACKGROUND: Stroke is one of the most disabling and burdensome health conditions
      worldwide, but no prospective population-based study has been conducted in Spain.
      Our aim was to assess age- and gender incidence rates of cerebrovascular disease,
      including stroke and transient ischemic attack, in three populations in central
      Spain using data from the NEDICES (Neurological Diseases in Central Spain), a
      population-based survey of elderly participants. METHODS: Individuals were
      evaluated at baseline (1994-1995) and at follow-up (a median of 3.2 years later
      in 1997-1998). The evaluation included a screening questionnaire for stroke and a
      neurological assessment (when possible). RESULTS: Of 5278 participants evaluated
      at baseline, there were 257 prevalent stroke cases. Seventy-five incident
      patients with cerebrovascular disease (57 stroke cases and 18 transient ischemic
      attacks cases) were identified among 3914 individuals assessed at follow-up.
      Average annual incidence rate (per 1000 person-years) in the population aged 65
      to 85 and over years, adjusted to the standard European population, was 5.1 (95%
      CI, 3.7 to 6.6) for all types of cerebrovascular disease. Age-specific incidence
      rates of cerebrovascular disease increased with advancing age. Age and diabetes
      mellitus were independent risk factors for cerebrovascular disease. Number of
      vascular risk factors present at baseline showed an independent positive and
      graded association with incident cerebrovascular disease. CONCLUSIONS: In the
      NEDICES study, incidence of cerebrovascular disease increased with age beyond age
      85. Our incidence rates provide new estimates for projection of future burden of
      disease in Spain.

PMID- 20817182
TI  - Comparing the predictive ability of population-specific Mini-Nutritional
      Assessment with Subjective Global Assessment for Taiwanese patients with
      hemodialysis: a cross-sectional study.
AB  - BACKGROUND: The Mini-Nutritional Assessment (MNA) and Subjective Global
      Assessment (SGA) are two frequently used tools in nutritional assessment.
      OBJECTIVES: This study aimed to evaluate the feasibility of applying the MNA with
      population-specific anthropometric modifications and to compare the predictive
      ability of MNA with that of the SGA in patients with hemodialysis. DESIGN:
      Purposive sampling. METHODS: This study was conducted in the Hemodialysis Unit of
      E-Da Hospital in Kaohsiung, Taiwan. A total of 192 patients with hemodialysis
      were evaluated their nutritional status concomitantly with the SGA and the MNA in
      two versions-MNA Taiwan version-I adopted population-specific anthropometric cut
      points, and MNA Taiwan version-II had body mass index (BMI) omitted. RESULTS: The
      SGA graded 1% malnourished and 51% at risk of malnutrition for patients with
      hemodialysis; MNA Taiwan version-I graded 3% and 41%, respectively, whereas MNA
      Taiwan version-II graded 5% and 36%, respectively. There were significant
      differences between patterns of nutritional status predicted with the SGA and the
      MNA versions (P<0.05). The scores predicted with both tools correlated positively
      with appetite, serum albumin and creatinine levels, BMI, and mid-arm and calf
      circumferences, and negatively with number of emergency visits. However, only MNA
      versions negatively correlated with length of hospital stay (all P<0.05). Linear
      regression analysis revealed that the MNA Taiwan version-I, -II and SGA scores
      were positively associated with BMI and serum albumin level, and negatively
      associated with number of emergency visits after adjusting for confounders (all
      P<0.05). However, only MNA Taiwan version-I and -II were negatively associated
      with C-reactive protein (CRP) level (P<0.05). The associations of MNA Taiwan
      version-II with albumin and CRP levels were stronger than those obtained using
      MNA Taiwan version-I and SGA. CONCLUSIONS: The present study suggests that both
      the modified MNA versions can evaluate nutritional risk of patients with
      hemodialysis in Taiwan. The MNA Taiwan version-II which adopted population
      specific anthropometric cut values without BMI is better able to assess
      nutritional status and reflect health status of patients with hemodialysis than
      MNA Taiwan version-I and SGA.

PMID- 20817181
TI  - Protective effects of transduced PEP-1-Frataxin protein on oxidative stress
      induced neuronal cell death.
AB  - Reactive oxygen species (ROS) actively contribute to the development of a number
      of human diseases including ischemia. In response to oxidative stress, frataxin
      has a significant ability to improve cell survival though its biological function
      is unclear in relation to ischemia. To explore frataxin's role in protecting
      against ischemic cell death, we constructed PEP-1-Frataxin cell-permeable fusion
      protein. In a dose- and time-dependent manner PEP-1-Frataxin rapidly transduced
      into astrocyte cells and protected them against oxidative stress-induced cell
      death. Further, using an animal model, immunohistochemical analysis revealed that
      PEP-1-Frataxin prevented neuronal cell death in the CA1 region of the hippocampus
      induced by transient forebrain ischemia. These results demonstrate that
      transduced PEP-1-Frataxin protects against cell death in vitro and in vivo,
      suggesting that transduction of PEP-1-Frataxin could be useful as a therapeutic
      agent for various human diseases related to oxidative stress.

PMID- 20817183
TI  - Psychometric properties of pain intensity scales comparing among postoperative
      adult patients, elderly patients without and with mild cognitive impairment in
      China.
AB  - BACKGROUND: Western studies have shown that patients with mild or moderate
      cognitive impairment (CI) can use pain intensity scales to report pain reliably
      and validly, however, the qualities of pain intensity scales use in various age
      groups including elderly with CI are varied. In China, there is a lack of
      studies. OBJECTIVE: To compare psychometric properties of five evidence-supported
      pain intensity scales including the Verbal Descriptor Scale (VDS), the Numeric
      Rating Scale (NRS), the Faces Pain Scale (FPS), the Numeric Box-21 Scale (BS-21),
      and the Colored Analogue Scale (CAS) in postoperative adults varying in ages
      including elderly with mild CI. DESIGN: Descriptive comparative study. SETTING: A
      university-affiliated hospital in China. PARTICIPANTS: Two hundred surgical
      patients were recruited purposively with 50 for each group: young adults, middle
      aged adults, elderly without CI, and elderly with mild CI. METHODS: Participants
      rated the vividly remembered, current, worst, least, and average pain, and
      indicated scale preference and simplicity. Scale face validity, concurrent
      validity, convergent validity, and test-retest reliability were assessed.
      Fisher's exact tests were used to investigate whether face validity was related
      to different age groups and levels of CI. One-way ANOVA and Kruskal-Wallis test
      were used to test the differences of concurrent validity, convergent validity,
      and test-retest reliability coefficients of each pain scale among the four
      groups. RESULTS: Regarding face validity, the FPS was ranked best as nearly half
      of the patients selected it as both the most preferred and simplest scale and it
      had low errors; the VDS and the NRS were ranked following the FPS; however, the
      BS-21 and the CAS were ranked last. The concurrent validity, convergent validity,
      and test-retest reliability of all five pain scales were supported in use with
      the four groups. The differences in psychometric properties among the four groups
      were only found in face validity and test-retest reliability. CONCLUSION: The
      findings support the psychometric properties of all five pain scales for pain
      assessment in Chinese adults including elderly with mild CI. However, the FPS
      appears to be the best, followed by the VDS and the NRS.

PMID- 20817184
TI  - European Society of Biomechanics S.M. Perren Award 2010: an adaptation mechanism
      for fibrous tissue to sustained shortening.
AB  - The mechanism by which fibrous tissues adapt upon alterations in their mechanical
      environment remains unresolved. Here, we determine that periosteum in chick
      embryos resides in an identical mechanical state, irrespective of the
      developmental stage. This state is characterized by a residual tissue strain that
      corresponds to the strain in between the pliant and stiffer region of the force
      strain curve. We demonstrate that periosteum is able to regain that mechanical
      equilibrium state in vitro, within three days upon perturbation of that
      equilibrium state. This adaptation process is not dependent on protein synthesis,
      because the addition of cycloheximide did not affect the response. However, a
      functional actin filament network is required, as is illustrated by a lack of
      adaptation in the presence of cytochalasin D. This led us to hypothesize that
      cells actively reduce collagen fiber crimp after tissue shortening, i.e. that in
      time the number of recruited fibers is increased via cell contraction. Support
      for this mechanism is found by visualization of fiber crimp with multiphoton
      microscopy before the perturbation and at different time points during the
      adaptive response.

PMID- 20817185
TI  - Fluid and solid mechanics in a poroelastic network induced by ultrasound.
AB  - We made a theoretical analysis on the fluid and solid mechanics in a poroelastic
      medium induced by low-power ultrasound. Using a perturbative approach, we were
      able to linearize the governing equations and obtain analytical solutions. We
      found that ultrasound could propagate in the medium as a mechanical wave, but
      would dissipate due to frictional forces between the fluid and the solid phase.
      The amplitude of the wave depends on the ultrasonic power input. We applied this
      model to the problem of drug delivery to soft biological tissues by low-power
      ultrasound and proposed a mechanism for enhanced drug penetration. We have also
      found the coexistence of two acoustic waves under certain circumstances and
      pointed out the importance of very accurate experimental determination of the
      high-frequency properties of brain tissue.

PMID- 20817186
TI  - Attenuation of diabetic nephropathy in diabetes rats induced by streptozotocin by
      regulating the endoplasmic reticulum stress inflammatory response.
AB  - The endoplasmic reticulum (ER) is capable of sensing metabolic and stress
      parameters and integrating intra- and extracellular signals to support a
      coordinated cell response. In the present study, we verified the hypothesis that
      4-phenylbutyric acid (4-PBA), a chemical chaperone, prevented the progression of
      diabetic nephropathy (DN). Male Sprague-Dawley rats were randomly divided into 3
      groups: a normal control group, a DN group, and a DN model plus 4-PBA treatment
      group (PBA). The DN model was induced by injection of streptozotocin with
      uninephrectomy. The dosage of 4-PBA treatment was gavaged at a dose of 1 g/kg
      body weight each day for 12 weeks. The expression of the ER stress indicators
      significantly increased in the kidney of DN rats within the indicated period.
      Moreover, the expression of phosphorylated c-JUN NH(2)-terminal kinase, the
      monocyte chemoattractant protein-1, and the final fibrotic effector all elevated
      markedly in the kidney of DN rats. Urinary protein excretion rate and the
      concentration of urinary monocyte chemoattractant protein-1 were higher than
      those in the normal control group. Treatment with 4-PBA can suppress the
      expression of the glucose-regulated protein 78 and the phosphorylation of the PKR
      like ER kinase, both of which are ER stress indicators; renoinflammatory signal;
      and the expression of inflammatory cytokines and fibrosis factors. It also can
      inhibit the increase in urinary protein excretion rate and urinary monocyte
      chemoattractant protein-1. In conclusion, 4-PBA exerts a marked renoprotective
      effect possibly due to modulating ER stress and related inflammatory cascade.

PMID- 20817187
TI  - Mitochondrial dysfunction during in vitro hepatocyte steatosis is reversed by
      omega-3 fatty acid-induced up-regulation of mitofusin 2.
AB  - We examined the effects and mechanisms of omega-3 polyunsaturated fatty acid
      (PUFA) administration on mitochondrial morphology and function in an in vitro
      steatotic hepatocyte model created using HepG2 cells. Reverse transcriptase
      polymerase chain reaction and Western blot analyses were performed to determine
      the expression levels of mitofusin 2 (Mfn2), and immunofluorescent MitoTracker
      Mitochondrion-Selective Probes were used to detect changes in mitochondrial
      morphology. Adenosine triphosphate (ATP) synthesis and reactive oxygen species
      (ROS) production were measured to assess mitochondrial function. Mitofusin 2
      expression was significantly suppressed (P < .05), ATP levels were decreased (P <
      .05), ROS production was increased (P < .05), and the normal tubular network of
      mitochondria was fragmented into short rods or spheres. Model cells were
      incubated with eicosapentaenoic acid or docosahexaenoic acid at a final
      concentration of 50 MUmol/L for 1 hour. Both eicosapentaenoic acid and
      docosahexaenoic acid increased the expression of Mfn2 (P < .01) and caused an
      increase in the length of mitochondrial tubules. The omega-3 PUFAs also increased
      the levels of ATP (P < .05) and decreased the ROS production (P < .05). However,
      these changes were not seen in Mfn2-depleted steatotic HepG2 cells, created by
      RNA interference before incubation with the omega-3 PUFAs. This study
      demonstrated that, in steatotic hepatocytes, omega-3 PUFAs may change
      mitochondrial morphology and have beneficial effects on recovery of mitochondrial
      function by increasing the expression of Mfn2.

PMID- 20817188
TI  - Microwave-assisted synthesis and reversed-phase high-performance liquid
      chromatographic separation of diastereomers of (R,S)-baclofen using ten chiral
      derivatizing reagents designed from trichloro-s-triazine.
AB  - Four dichloro-s-triazine (DCT) and five monochloro-s-triazine (MCT) chiral
      derivatizing reagents (CDRs) were synthesized by incorporating amino acid amide
      moieties as chiral auxiliaries in trichloro-s-triazine and its 6-methoxy
      derivative, respectively. Another MCT reagent was synthesized by substitution of
      two chlorine atoms with two different amino acid amides in trichloro-s-triazine.
      These reagents were used for synthesis of diastereomers of (R,S)-baclofen under
      microwave irradiation (i.e. 60 s at 85% power using DCT reagents and 90 s at 85%
      power using MCT reagents). The diastereomers were separated on a reversed-phase
      C18 column using mixtures of methanol with aqueous trifluoroacetic acid (TFA)
      with UV detection at 230 nm. The separation behavior in terms of retention times
      and resolutions obtained for the two sets of diastereomers prepared with DCT and
      MCT reagents were compared among themselves and among the two groups. Longer
      retention times and better resolutions were observed with DCT reagents as
      compared to MCT reagents. The calibration curves were linear for both (R)- and
      (S)-baclofen in the concentration range 50-500 MUg/ml. The average regression was
      0.999 for both (R)- and (S)-baclofen. The RSD for (R)-baclofen was 0.40-0.86% for
      intra-day precision and 0.60-1.40% for inter-day precision and these values for
      (S)-baclofen were 0.52-0.75% and 0.64-1.32%, respectively. The recovery was 97.2
      98.9% for (R)- and 97.0-98.9% for (S)-baclofen. The limit of detection was 1.63
      ng/ml and 1.52 ng/ml for (R)- and (S)-baclofen, respectively.

PMID- 20817189
TI  - Determination of synthetic phenolic antioxidants and their metabolites in water
      samples by downscaled solid-phase extraction, silylation and gas chromatography
      mass spectrometry.
AB  - The development and performance evaluation of an analytical method dedicated to
      the comprehensive determination of the most relevant antioxidants and their
      metabolites in aqueous environmental samples is presented. This was achieved by a
      miniaturised solid-phase extraction (SPE) with 10mg Oasis HLB cartridges, which
      allow to achieve a concentration factor of 200, reducing organic solvent wastes
      (1 mL of ethyl acetate suffices for complete elution) and SPE costs and
      eliminating the need for solvent evaporation that otherwise compromises the
      recoveries of butylated hydroxytoluene (BHT) and 2,6-di-tert-butylcyclohexa-2,5
      diene-1,4-dione (BHT-Q). Analytes were then determined by gas chromatography-mass
      spectrometry (GC-MS) after derivatisation with N-methyl-N-(tert
      butyldimethylsilyl)-trifluoroacetamide (MTBSTFA) in a single run. BHT-d(7) and n
      propyl-paraben-d(4) (PrP-d(4)) were used as surrogate internal standards. These
      surrogates allowed obtaining relative recoveries in the 80-110% range for all
      analytes even with complex wastewater samples and LODs at the 2-44 ngL(-1) level
      taking into account blank issues often associated to antioxidants analysis. The
      method was applied to sewage and river waters, showing that the seven analytes
      could be detected in raw wastewater. BHT and BHT-Q were the most concentrated
      species in that type of sample (in the 275-871 ngL(-1) range). On the other hand
      two metabolites of BHT, 3,5-di-tert-butyl-4-hydroxybenzaldehyde (BHT-CHO) and 3,5
      di-tert-butyl-4-hydroxybenzoic acid (BHT-COOH) appeared to be the most ubiquitous
      species, being found in all samples in the 10-150 ngL(-1) concentration range.

PMID- 20817190
TI  - Optimization of a high-performance liquid chromatography method for the analysis
      of complex polyphenol mixtures and application for sainfoin extracts (Onobrychis
      viciifolia).
AB  - A pentafluorophenylpropyl (PFP) stationary phase was tested for the simultaneous
      determination of several classes of phenolic compounds. The chromatographic
      results were compared with those obtained by using a bifunctional phase
      constituted of octadecyl and phenylpropyl bonded silica and three conventional
      C18 columns. The elution gradient was optimized with 5% formic acid and sodium
      acetate in combination with acetic acid as additives and methanol as solvents.
      For these evaluations, a complex phenolic extract of Onobrychis viciifolia
      (sainfoin) and test mixtures containing 54 standard substances including 2 simple
      phenolic compounds, 1 amino acid, 4 hydroxybenzoic acids (HBA), 6 hydroxycinnamic
      acids (HCA), 3 flavan-3-ols, 9 anthocyanins, 2 dihydroflavonols, 1 chalcone, 4
      flavones, 1 isoflavone and 21 flavonols have been assayed. The perfluorinated
      column showed good resolution for the studied phenolic compounds which have the
      following elution order: HBA, HCA, flavan-3-ols, anthocyanins, dihydroflavonols,
      flavones, flavonols and isoflavones. Compared with other columns, it provides
      longer elution ranges for HBA, HCA and flavan-3-ols and increased retention times
      for all compound classes except anthocyanins which were similarly retained on a
      C18 column. Its selectivity is different from C18 and bifunctional phases. A high
      performance liquid chromatography (HPLC) method with diode array detection (DAD)
      and post-column derivatization with p-dimethyl-aminocinnamic aldehyde (DMACA) has
      been validated for the analysis of individual phenolic compounds from a sainfoin
      plant extract (O. viciifolia).

PMID- 20817191
TI  - Coacervative microextraction ultrasound-assisted back-extraction technique for
      determination of organophosphates pesticides in honey samples by gas
      chromatography-mass spectrometry.
AB  - Coacervative microextraction ultrasound-assisted back-extraction technique (CME
      UABE) is proposed for the first time for extracting and preconcentrating
      organophosphates pesticides (OPPs) from honey samples prior to gas chromatography
      mass spectrometry (GC-MS) analysis. The extraction/preconcentration technique is
      supported on the micellar organized medium based on non-ionic surfactant. To
      enable coupling the proposed technique with GC, it was required to back extract
      the analytes into hexane. Several variables including, surfactant type and
      concentration, equilibration temperature and time, matrix modifiers, pH and
      buffers nature were studied and optimized over the relative response of the
      analytes. The best working conditions were as follows: an aliquot of 10 mL 50 gL(
      1) honey blend solution was conditioned by adding 100 MUL 0.1 molL(-1)
      hydrochloric acid (pH 2) and finally extracted with 100 MUL Triton X-114 100 gL(
      1) at 85 degrees C for 5 min using CME technique. Under optimal experimental
      conditions, the enrichment factor (EF) was 167 and limits of detection (LODs),
      calculated as three times the signal-to-noise ratio (S/N=3), ranged between 0.03
      and 0.47 ngg(-1). The method precision was evaluated over five replicates at 1
      ngg(-1) with RSDs <= 9.5%. The calibration graphs were linear within the
      concentration range of 0.3-1000 ngg(-1) for chlorpirifos; and 1-1000 ngg(-1) for
      fenitrothion, parathion and methidathion, respectively. The coefficients of
      correlation were >= 0.9992. Validation of the methodology was performed by
      standard addition method at two concentration levels (2 and 20 ngg(-1)). The
      recoveries were >= 90%, indicating satisfactory robustness of the methodology,
      which could be successfully applied for determination of OPPs in honey samples of
      different Argentinean regions. Two of the analyzed samples showed levels of
      methidathion ranged between 1.2 and 2.3 ngg(-1).

PMID- 20817192
TI  - [Glioblastomas: gliomagenesis, genetics, angiogenesis, and microenvironment].
AB  - BACKGROUND AND PURPOSE: Glioblastomas are the most malignant gliomas of the
      central nervous system. Currently, numerous studies are attempting to decipher
      their genetic and epigenetic modifications, to identify the cells at the origin
      of gliomagenesis, and to better understand the molecular bases responsible for
      invasion and angiogenesis processes. METHODS: This article reviews recent data on
      the cellular and molecular biology of gliomas delineated by several teams
      including ours. We and others have underlined the role played by cancer stem
      cells in gliomagenesis; the Cancer Genome Atlas Network has described most
      glioblastoma genetic alterations. RESULTS: According to many studies,
      glioblastomas derive from malignant transformation of stem cells and/or glial
      precursor cells. Moreover, the topographic microenvironment is important
      regarding invasion and angiogenesis processes. Finally, it is now well
      established, thanks to IDH1 mutation identification, that primary and secondary
      glioblastomas are two different clinical and genetic entities. Interestingly,
      IDH1 mutation seems to be a very early genomic modification in astrocytoma,
      oligodendroglioma, and secondary glioblastoma tumorigenic processes. CONCLUSIONS:
      Regarding all these data, we suggest a hypothetical model of glioma initiation,
      growth, and progression. Moreover, the histomolecular glioma classification has
      been substantially revised and new therapeutic targets have been identified.

PMID- 20817193
TI  - Preparation of gold patterns on polyimide coating via layer-by-layer deposition
      of gold nanoparticles.
AB  - Gold patterns were prepared via the microcontact printing (MCP) of 3
      aminopropyltriethoxysilane (gamma-APS) on plasma etched polyimide films, followed
      by the layer-by-layer (LBL) deposition of gold nanoparticles (GNPs), O(2) plasma
      etching, and sintering. First, the polyimide film on silicon wafer was modified
      via water plasma etching, followed by the MCP of gamma-APS using a flat
      polydimethylsiloxane (PDMS) stamp. Next, the multilayer of GNPs was formed on the
      gamma-APS layer by the LBL deposition of citrate-capped GNPs and
      poly(ethyleneimine) (PEI). Then, the samples were subjected to O(2) plasma
      etching to remove PEI and citrates, and then sintering to produce metallic gold.
      Finally, gold patterns were prepared with a patterned PDMS stamp (line width of
      10MUm). The GNP multilayer was characterized by UV-vis/near-IR spectrometer,
      atomic force microscopy (AFM), optical microscopy (OM), alpha-step and electrical
      conductivity measurement by two-point probe method. Very clean gold patterns with
      electrical conductivity of 4.1*10(4)Omega(-1)cm(-1) (20-layer GNP) were obtained.

PMID- 20817194
TI  - Crystal lattice imaging of the silica and alumina faces of kaolinite using atomic
      force microscopy.
AB  - The crystal lattice images of the two faces of kaolinite (the silica face and the
      alumina face) have been obtained using contact-mode atomic force microscopy (AFM)
      under ambient conditions. Lattice resolution images reveal the hexagonal surface
      lattice of these two faces of kaolinite. Analysis of the silica face of kaolinite
      showed that the hexagonal surface lattice ring of oxygen atoms had a periodicity
      of 0.50+/-0.04nm between neighboring oxygen atoms, which is in good agreement
      with the surface lattice structure of the mica basal plane. The center of the
      hexagonal ring of oxygen atoms is vacant. Analysis of the alumina face of
      kaolinite showed that the hexagonal surface lattice ring of hydroxyls surround a
      hydroxyl in the center of the ring. The atomic spacing between neighboring
      hydroxyls was determined as 0.36+/-0.04nm. Ordering of the kaolinite particles
      for examination of the silica and alumina surfaces was accomplished using
      different substrates, a procedure previously established. Crystal lattice imaging
      supports previous results and independently confirms that the two faces of
      kaolinite have been properly identified.

PMID- 20817195
TI  - O/W emulsions stabilised by both low molecular weight surfactants and colloidal
      particles: The effect of surfactant type and concentration.
AB  - The stability against coalescence of O/W emulsions in the presence of both
      surfactants and colloidal particles was investigated. In particular the effect of
      the surfactant type and concentration in these emulsifier mixtures on the O/W
      emulsions' stability was studied. Two types of surfactants were selected; those
      that have the ability to stabilise O/W emulsions on their own (O/W surfactants)
      and those that cannot (W/O surfactants). Tween 60 and Sodium Caseinate were
      selected as the O/W surfactants and lecithin as the W/O surfactant. Oil-in-water
      emulsions prepared with both particles and any of the three surfactants were
      stable against coalescence but, depending on the type of surfactant, the
      behaviour of the systems was found to depend on surfactant concentration. The
      droplet sizes of emulsions stabilised by mixed emulsifier systems containing low
      concentrations of O/W surfactants (Tween 60 or Sodium Caseinate) were smaller
      than those solely stabilised by either the surfactant or particles alone. At
      intermediate O/W surfactants concentrations, the droplet sizes of the emulsions
      increased. Further increases in the O/W surfactants' concentration, resulted in
      the complete removal of particles from the interface with the system now behaving
      as a surfactant-only stabilised emulsion. The behaviour of emulsions stabilised
      by emulsifier mixtures containing W/O surfactants was not dependent on the
      concentration of surfactant: no removal of particles was observed.

PMID- 20817196
TI  - Dispersion of single walled carbon nanotubes in organogels by incorporation into
      organogel fibers.
AB  - We prepared hybrid organogels, where single walled carbon nanotubes (SWNTs) were
      incorporated into organogel fibers. The SWNTs were covalently functionalized with
      organic branches that had a similar structure to the organogelator. The effect of
      relative interactions between the carbon nanotubes (CNTs), organogelator, and
      solvent molecules on the hybrid organogel structure was investigated. Compounds 1
      and 2 were synthesized from 3,4,5-tris(decyloxy)benzoic acid and 1,8
      diaminooctane, as an organogelator and a functional group for SWNTs,
      respectively. Organogelator 1 showed excellent ability to gelate alkanes and
      alcohols. The pristine SWNTs were oxidized by acids to create carboxylic acid
      groups and functionalized covalently with compound 2 using thionyl chloride.
      Hybrid organogels of compound 1 with functionalized SWNTs (f-SWNTs) were prepared
      in decane and N,N-dimethylformamide (DMF). Transmission electron microscopy (TEM)
      images showed that the f-SWNTs in the hybrid organogel formed in decane were
      mainly located inside or on the surface of the organogel fibers, while the f
      SWNTs in the hybrid organogel formed in DMF were distributed evenly over the
      sample. When an organogelator had a different chemical structure to that of an
      organic functional group on the SWNT surface, SWNTs existed as large aggregates,
      or long bundles, which were not incorporated inside of the organogel fibers.

PMID- 20817197
TI  - Synthesis of hydrophilic and organophilic chemically modified graphene oxide
      sheets.
AB  - In this work, hydrophilic and organophilic chemically modified graphene oxide
      (CMGO) sheets were prepared through a two-step diimide-activated amidation. The
      hydrophilic and organophilic products were characterized by atomic force
      microscopy, transmission electron microscopy and ultraviolet-visible
      spectroscopy. The resulted dispersions are homogeneous and exhibit long-term
      stability, which will facilitate the combination of CMGO sheets with polymers to
      yield homogeneous composites.

PMID- 20817198
TI  - Dip coating of charged colloidal suspensions onto substrates with patterned
      wettability: Coating regime maps.
AB  - Aqueous dispersions of silica nanoparticles were dip coated onto Si substrates
      that contained patterned wettability. The patterns were prepared by
      photolithography and consisted of groups of hydrophilic lines (5-100MUm wide)
      separated by hydrophobic areas (5-100MUm wide). Coating were made from two
      aqueous silica dispersions: a cationic dispersion in which particles have
      positive surface charge, and an anionic dispersion in which particles have
      negative surface charge. Coating morphology, thickness, and pattern quality were
      characterized. For a pattern containing 25MUm wide hydrophilic stripes separated
      by equally wide hydrophobic spaces, coating regime maps were created to show the
      effect of process variables on pattern features and morphology. Within the map
      there is a critical concentration for both dispersions, above which uniform
      stripes are formed and below which a segregated non-uniform structure results.
      Coatings prepared at withdrawal rates of 0.1mm/s or lower resulted in a monolayer
      of coatings in the case of cationic silica and no deposition in the case of
      anionic silica. A maximum withdrawal rate was also found; above a critical speed,
      excess liquid is entrained and results in nonuniformity in the bottom of the
      pattern. The physical origin of the regimes and differences between the two types
      of particles are discussed.

PMID- 20817200
TI  - Rupture and dewetting of water films on solid surfaces.
AB  - An experimental study was conducted to observe rupture and dewetting of water
      films, 0.5-2mm thick, on solid surfaces. The effects of surface roughness,
      wettability, protrusions on surfaces, and air entrapment between films and
      surfaces were studied. Film thickness measurements were made and film rupture and
      surface dewetting photographed. Experiments showed that liquid films ruptured
      first along the highest edges of test surfaces. Placing a protrusion on the
      surface had no effect-the liquid film continued to rupture along the edges. A
      thermodynamic model was developed to show that protrusions lower the surface
      energy of the system and promote wetting. Increasing surface roughness therefore
      increases film stability by resisting rupture and dewetting. Water films could be
      punctured by introducing an air bubble that burst and created a hole. The hole
      would close if the film was thick and the solid-liquid contact angle was either
      small or large; the hole would grow larger if the film was thin and the contact
      angle was in the mid-range (~80 degrees ). An analytical model that calculates
      the difference between the surface energies of the two states can be used to
      predict whether a hole would lead to surface dewetting or not.

PMID- 20817199
TI  - Copper complexed polymer carriers for IgG adsorption.
AB  - Cost effective adsorption matrix is recently, a much sought after alternative to
      the normal and expensive forms of matrices that are being used for the separation
      and purification of therapeutic molecules like immunoglobulins. A study
      therefore, has been focussed on developing copper complexed poly (vinyl alcohol)
      [PVA] and poly (styrene allyl alcohol) [PSA] gel beads for the separation of
      immunoglobulin G (IgG) from aqueous solutions. The copper-immobilized PVA and PSA
      gel beads were prepared, characterized and the copper content was estimated using
      EDX analysis. Further compatibility tests such as erythrocyte aggregation, lyses
      and cell counting were also investigated. An increase in the IgG adsorption
      capacities was achieved with the copper immobilized micro particles, when
      compared with the unmodified particles.

PMID- 20817201
TI  - [Unusual mandibular osteolysis].

PMID- 20817202
TI  - [Leiomyosarcoma of the parotid gland].
AB  - INTRODUCTION: Primary leiomyosarcoma of the parotid gland is an extremely rare
      neoplasm, develops from smooth muscle cells. Its primary origin in the face and
      especially in the salivary glands is even more rare. CASE REPORT: A 15-year-old
      boy, with no prior history was hospitalized for swelling in the left parotid area
      having appeared 5 months before. The mass was painless and there was no facial
      paralysis. CT scan showed a tumoral process of mixed density in the left parotid
      gland. Thoracoabdominal CT scan was normal. Conservative parotidectomy was
      performed. The histological diagnosis was primary leiomyosarcoma of the parotid
      gland. DISCUSSION: Five per cent of salivary gland primitive tumors are of
      mesenchymatous origin, of which 0.3 to 1.5% are sarcoma. The diagnosis of
      leiomyosarcoma of the parotid gland is confirmed by histological and
      immunohistochemical assessment. Surgery sometimes combined to radiochemotherapy
      seems to be the treatment of choice.

PMID- 20817203
TI  - Developmental changes in multivariate neuroanatomical patterns that predict risk
      for psychosis in 22q11.2 deletion syndrome.
AB  - The primary objective of the current prospective study was to examine
      developmental patterns of voxel-by-voxel gray and white matter volumes (GMV, WMV,
      respectively) that would predict psychosis in adolescents with 22q11.2 deletion
      syndrome (22q11.2DS), the most common known genetic risk factor for
      schizophrenia. We performed a longitudinal voxel-based morphometry analysis using
      structural T1 MRI scans from 19 individuals with 22q11.2DS and 18 typically
      developing individuals. In 22q11.2DS, univariate analysis showed that greater
      reduction in left dorsal prefrontal cortical (dPFC) GMV over time predicted
      greater psychotic symptoms at Time2. This dPFC region also showed significantly
      reduced volumes in 22q11.2DS compared to typically developing individuals at
      Time1 and 2, greater reduction over time in 22q11.2DS COMT(Met) compared to
      COMT(Val), and greater reduction in those with greater decline in verbal IQ over
      time. Leave-one-out Multivariate pattern analysis results (MVPA) on the other
      hand, showed that patterns of GM and WM morphometric changes over time in regions
      including but not limited to the dPFC predicted risk for psychotic symptoms (94.7
      100% accuracy) significantly better than using univariate analysis (63.1%).
      Additional predictive brain regions included medial PFC and dorsal cingulum. This
      longitudinal prospective study shows novel evidence of morphometric spatial
      patterns predicting the development of psychotic symptoms in 22q11.2DS, and
      further elucidates the abnormal maturational processes in 22q11.2DS. The use of
      neuroimaging using MVPA may hold promise to predict outcome in a variety of
      neuropsychiatric disorders.

PMID- 20817204
TI  - NeoGemOx: Gemcitabine and oxaliplatin as neoadjuvant treatment for locally
      advanced, nonmetastasized pancreatic cancer.
AB  - BACKGROUND: Neoadjuvant chemotherapy can facilitate pancreatic resection in
      patients with initially unresectable pancreatic cancer (PC). We report the
      results of a phase II trial of gemcitabine-oxaliplatin neoadjuvant chemotherapy
      for patients with locally advanced, nonmetastatic PC. METHODS: A prospective,
      phase II clinical trial using neoadjuvant chemotherapy, consisting of gemcitabine
      (900 mg/m(2)) and oxaliplatin (60 mg/m(2)) given as intravenous infusion once a
      week at day 1 of each treatment cycle (NeoGemOx protocol). Patients received 6-9
      cycles of chemotherapy. Those patients with sufficient tumor regression
      subsequently underwent pancreatic resection and were followed postoperatively to
      assess long-term survival. RESULTS: A total of 33 patients were eligible and were
      included in the intent-to-treat and evaluable population. On centralized review
      of the imaging studies, 18 patients had unresectable disease at inclusion, and 15
      patients had borderline resectable PC. Eventually, 13 patients (39%) had a
      curative resection after neoadjuvant therapy. The R0 resection rate was 69%.
      Median overall survival of patients who underwent tumor resection was 22 months
      (95% confidence interval [CI], 14-30) compared with 12 months (95% CI, 9-15) for
      those without resection (P = .046). The median recurrence-free survival rate
      after resection was 10 months (95% CI, 4-17). CONCLUSION: Neoadjuvant gemcitabine
      plus oxaliplatin is well tolerated and safe. Substantive tumor regression occurs
      in some patients with locally advanced PC treated with this neoadjuvant protocol,
      offering the potential for curative resection and improvement in overall
      survival. Additional studies involving the NeoGemOx protocol should be considered
      to further evaluate the safety and efficacy of this combination.

PMID- 20817205
TI  - Operative treatment for metachronous pulmonary metastasis from esophageal
      carcinoma.
AB  - BACKGROUND: The clinical significance of operative treatment for metachronous
      pulmonary metastasis from esophageal carcinoma is unclear. METHODS: We
      retrospectively reviewed 23 consecutive patients who underwent operative
      resection for metachronous pulmonary metastasis from esophageal carcinoma from
      1991 to 2008. Patient baseline characteristics, survival probability, and
      prognostic factors were analyzed. The median follow-up period was 31 months for
      surviving patients. RESULTS: There were 19 men and 4 women, with a median age of
      66 years at the time of pulmonary resection. The median disease-free interval was
      15.5 months. Cervical or mediastinal lymph node metastases preceded pulmonary
      metastases in 4 patients. Seven patients (30.4%) had multiple metastases with a
      maximum number of 4. The median operative time and blood loss were 94.5 minutes
      and 18 mL, respectively. The median length of postoperative stay was 12.5 days.
      The predicted 1-, 3-, and 5-year survival rates using the Kaplan-Meier method
      were 73.9%, 43.5%, and 43.5%, respectively, with a median survival time of 28.7
      months. Univariate analysis revealed that an extrapulmonary metastasis as the
      initial recurrence site was an unfavorable prognostic factor (P = .0411).
      Multivariate analyses, however, did not identify the initial recurrence site as
      an independent prognostic factor (P = .0542). CONCLUSION: Operative resection for
      metachronous pulmonary metastasis from esophageal carcinoma is an acceptable
      treatment. This study of a limited number of patients may have created a
      constitutional selection bias. An antecedent extrapulmonary metastasis was found
      to be an unfavorable prognostic factor.

PMID- 20817206
TI  - Humoral autoimmunity in multiple sclerosis.
AB  - The important role of B cells and autoantibodies in the pathogenesis of MS is
      increasingly appreciated. The recruitment and maintenance of B cells and plasma
      cells in MS lesions is presumably based on local production of lymphoid
      chemokines and B cell activation factor of the TNF family (BAFF). The failure of
      the clinical trial with Atacicept targeting BAFF and its relative APRIL was a
      great surprise and cannot readily be explained. A role for BAFF in CNS
      physiology, e.g. via targeting of the Nogo-66 receptor might have to be
      considered. The identification of patient subgroups based on autoantibodies is a
      future challenge. Currently patients with neuromyelitis optica (NMO) can be
      identified by antibodies to aquaporin 4 and about a third of children with
      acquired demyelinating diseases have antibodies against conformationally correct
      MOG, while such antibodies are hardly found in adult MS patients. Searching for
      new targets of the autoimmune response in adult MS patients, we have identified
      two axo-glial proteins focused around the node of Ranvier, namely neurofascin and
      contactin-2/TAG-1. Testing the functional relevance of such an autoimmune
      response in animal models revealed that antibodies to neurofascin may induce
      axonal injury and that T cells specific for contactin-2/TAG-1 mediate
      preferentially gray matter injury.

PMID- 20817207
TI  - Absorbable pulmonary arterial banding: an optimal strategy for muscular or
      residual ventricular septal defects.

PMID- 20817208
TI  - Seasonality of hypoplastic left heart syndrome in the United States: a 10-year
      time-series analysis.
AB  - OBJECTIVE: Hypoplastic left heart syndrome is a major congenital heart defect and
      is associated with significant morbidity and mortality. Its etiology remains
      unknown although genetic studies imply complex inheritance. Anecdotal reports of
      cluster presentations suggest the possible involvement of an environmental
      component, although previous epidemiologic studies have been of limited scope.
      The objective of this study was to examine seasonal and temporal patterns of
      hypoplastic left heart syndrome births compared with other left-sided heart
      defects in the United States. METHODS: We conducted a retrospective analysis of
      the Pediatric Health Information System inpatient database from pediatric
      hospitals across the country from 1996 to 2006. Population and index case
      patterns were analyzed for each diagnostic category. An epidemiologic survey was
      performed through time-series analyses using Fisher's Kappa test and the Bartlett
      Kolmogorov-Smirnov test. The existence and strength of seasonality for the left
      sided heart defects was quantified by the autoregression R2. RESULTS: A seasonal
      occurrence was found in hypoplastic left heart syndrome but not other left-sided
      heart diseases. Significant seasonal differences occurred each year, with peaks
      in summer months and troughs in winter months. The seasonality inversely
      correlated with the incidence of chromosomal and extracardiac anomalies; such
      anomalies were highest in interrupted aortic arch, which had a random pattern of
      presentation. CONCLUSIONS: There is a significant seasonal pattern in the
      presentation of hypoplastic left heart syndrome, with preponderance in summer
      months, in contrast to the random pattern in other left-sided heart diseases.
      Further studies are warranted to identify the influence of potential
      environmental factor(s) in hypoplastic left heart syndrome, as seen in diseases
      with seasonal patterns.

PMID- 20817209
TI  - Comparison of the effectiveness and safety of a new de-airing technique with a
      standardized carbon dioxide insufflation technique in open left heart surgery: a
      randomized clinical trial.
AB  - OBJECTIVE: We have compared the effectiveness, time required for de-airing, and
      safety of a newly developed de-airing technique for open left heart surgery (Lund
      technique) with a standardized carbon dioxide insufflation technique. METHODS:
      Twenty patients undergoing elective open aortic valve surgery were randomized
      prospectively to the Lund technique (Lund group, n = 10) or the carbon dioxide
      insufflation technique (carbon dioxide group, n = 10). Both groups were monitored
      intraoperatively during de-airing and for 10 minutes after weaning from
      cardiopulmonary bypass by transesophageal echocardiography and online
      transcranial Doppler for the severity and the number of gas emboli, respectively.
      The systemic arterial partial pressure of carbon dioxide and pH were also
      monitored in both groups before, during, and after cardiopulmonary bypass.
      RESULTS: The severity of gas emboli observed on transesophageal echocardiography
      and the number of microembolic signals recorded by transcranial Doppler were
      significantly lower in the Lund group during the de-airing procedure (P = .00634)
      and in the first 10 minutes after weaning from cardiopulmonary bypass (P =
      .000377). Furthermore, the de-airing time was significantly shorter in the Lund
      group (9 vs 15 minutes, P = .001). The arterial pH during the cooling phase of
      cardiopulmonary bypass was significantly lower in the carbon dioxide group (P =
      .00351), corresponding to significantly higher arterial partial pressure of
      carbon dioxide (P = .005196) despite significantly higher gas flows (P = .0398)
      in the oxygenator throughout the entire period of cardiopulmonary bypass.
      CONCLUSIONS: The Lund de-airing technique is safer, simpler, and more effective
      compared with the carbon dioxide insufflation technique. The technique is also
      more cost-effective because the de-airing time is shorter and no extra expenses
      are incurred.

PMID- 20817210
TI  - Behavior of polymeric substrates in an aerobic granular sludge system.
AB  - Particulate and slowly biodegradable substrates form an important fraction of
      industrial wastewater and sewage. To study the influence of suspended solids and
      colloidal substrate on the morphology and performance of aerobic granular sludge,
      suspended and soluble starch was used as a model substrate. Degradation was
      studied using microscopy, micro-electrode measurements, batch experiments and
      long term laboratory scale reactor operation. Starch was removed by adsorption at
      the granule surface, followed by hydrolysis and consumption of the hydrolyzed
      products. Aerobic granules could be maintained on starch as sole influent carbon
      source, but their structure was filamentous and irregular. It is hypothesized
      that this is related to the low starch hydrolysis rates, leading to available
      substrate during the aeration period (extended feast period) and resulting in
      increased substrate gradients over the granules. The latter induces a less
      uniform granule development. Starch adsorbed and was consumed at the granule
      surface instead of being accumulated inside the granules as occurs for soluble
      substrates. Therefore the simultaneous denitrification efficiencies remained low.
      Moreover, many protozoa and metazoans were observed in laboratory reactors as
      well as in pilot- and full-scale Nereda((r)) reactors, indicating an important
      role in the removal of suspended solids too.

PMID- 20817211
TI  - Periodontal disease and hypertriglyceridemia in Japanese subjects: potential
      association with enhanced lipolysis.
AB  - Although periodontal disease may be associated with increased risk for
      atherosclerosis, the mechanism by which the disease causes atherosclerosis is
      still unknown. The candidates contributing to atherosclerosis in periodontal
      disease include low-grade inflammation such as C-reactive protein (CRP) and
      insulin resistance. A previous study demonstrated that periodontal therapy leads
      to an improvement in CRP as well as insulin resistance, indicating the
      relationship between periodontal disease and low-grade inflammation or insulin
      resistance. On the other hand, we previously demonstrated that serum triglyceride
      (TG) per se is independently associated with CRP or insulin resistance in
      Japanese populations with a body mass index (BMI) of 21.5 to 27.0 (midrange BMI).
      To the best of our knowledge, however, the relationship between periodontal
      disease and serum TG is not fully clarified. The first aim of the present study
      is to investigate whether periodontal disease is associated with serum TG in
      Japanese subjects with midrange BMI. If so, another aim of the study is to
      determine which mechanism is responsible for the association between periodontal
      disease and serum TG in these subjects. We have performed a periodontal
      examination in the Ogaki metabolic syndrome medical examination. One hundred
      sixty-two participants from 40 to 74 years old (56 men and 106 women; mean age,
      66.43 +/- 6.25 years) were enrolled in the study. Besides medical examination,
      oral panoramic radiograph was taken for all participants. Average bone score was
      also calculated. Periodontal bone destruction increased according to the age of
      the participants (r = 0.227, P < .004, Spearman correlation coefficient).
      Periodontal bone destruction was also associated with serum TG levels (r = 0.299,
      P = .000). This association was more evident in subjects with midrange BMI (r =
      0.332, P < .001). In subjects with midrange BMI, TG was not correlated with BMI
      or waste circumstances. Furthermore, TG was not associated with age itself in the
      midrange BMI group. We then investigated the lipolytic activity of endotoxin in
      cocultures of adipocytes and macrophages. Low-dose lipopolysaccharide dose
      dependently increased lipolytic activity in cocultures, and this activity was
      neutralized by anti-tumor necrosis factor alpha neutralizing antibodies. These
      results suggest that periodontal infection, especially bacterial endotoxinemia,
      is associated with enhanced lipolysis and subsequent up-regulation of circulating
      TG in Japanese with midrange BMI.

PMID- 20817212
TI  - Constitutively active heat shock factor 1 enhances glucose-driven insulin
      secretion.
AB  - Weak pancreatic beta-cell function is a cause of type 2 diabetes mellitus.
      Glucokinase regulates insulin secretion via phosphorylation of glucose. The
      present study focused on a system for the self-protection of pancreatic cell by
      expressing heat shock factor (HSF) and heat shock protein (HSP) to improve
      insulin secretion without inducing hypoglycemia. We previously generated a
      constitutively active form of human HSF1 (CA-hHSF1). An adenovirus expressing CA
      hHSF1 using the cytomegalovirus promoter was generated to infect mouse insulinoma
      cells (MIN6 cells). An adenovirus expressing CA-hHSF1 using a human insulin
      promoter (Ins-CA-hHSF1) was also generated to infect rats. We investigated
      whether CA-hHSF1 induces insulin secretion in MIN6 cells and whether Ins-CA-hHSF1
      can improve blood glucose and serum insulin levels in healthy Wister rats and
      type 2 diabetes mellitus model rats. CA-hHSF1 expression increased insulin
      secretion 1.27-fold compared with the overexpression of wild-type hHSF1 in MIN6
      cells via induction of HSP90 expression and subsequent activation of glucokinase.
      This mechanism is associated with activation of both glucokinase and neuronal
      nitric oxide synthase. Ins-CA-hHSF1 improved blood glucose levels in neonatal
      streptozotocin-induced diabetic rats. Furthermore, Ins-CA-hHSF1 reduced oral
      glucose tolerance testing results in healthy Wister rats because of an insulin
      spike at 15 minutes; however, it did not induce hypoglycemia. CA-hHSF1 induced
      insulin secretion both in vitro and in vivo. These findings suggest that gene
      therapy with Ins-CA-hHSF1 will be able to be used to treat patients with type 2
      diabetes mellitus and impaired glucose tolerance without causing hypoglycemia at
      fasting.

PMID- 20817213
TI  - Nonalcoholic steatohepatitis and increased risk of chronic kidney disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) share
      common features. Both are associated with visceral obesity, type 2 diabetes
      mellitus, metabolic syndrome, and insulin resistance. However, the relationship
      between NAFLD and CKD is poorly understood. We examined the prevalence of and
      risk factors for CKD in patients with NAFLD. We analyzed 174 Japanese patients
      with liver biopsy-proven NAFLD using a cross-sectional design. Chronic kidney
      disease was defined as estimated glomerular filtration rate less than 60 mL/min
      per 1.73 m(2) and/or overt proteinuria. Of 174 NAFLD patients, 92 (53%) exhibited
      histologic characteristics of nonalcoholic steatohepatitis (NASH), the
      progressive form of NAFLD; and 82 (47%) had non-NASH NAFLD. Chronic kidney
      disease was present in 24 (14%) of 174 NAFLD patients. The prevalence of CKD was
      significantly higher in NASH patients (19 of 92; 21%) than non-NASH patients (5
      of 82; 6%). The presence of CKD was associated with a higher body mass index and
      the presence of hypertension and NASH. Our results demonstrated a high prevalence
      of CKD among patients with NASH.

PMID- 20817214
TI  - Effect of collagen I and aortic carboxypeptidase-like protein on 3T3-L1 adipocyte
      differentiation.
AB  - Aortic carboxypeptidase-like protein (ACLP) is a secreted protein expressed in
      preadipocytes and down-regulated during adipogenesis. Results from previous
      studies on the influence of ACLP overexpression on adipogenesis vary from no
      effect to complete inhibition. We hypothesized that ACLP may modulate
      adipogenesis in the presence of collagen I, a protein to which it binds. We
      compared control (pLXSN) 3T3-L1 preadipocytes with 3T3-L1 preadipocytes stably
      overexpressing ACLP (pLXSN-ACLP) that were grown in standard vs collagen I-coated
      dishes. Aortic carboxypeptidase-like protein overexpression, via retroviral
      transduction, resulted in a 3.2-fold increase in ACLP cellular levels and a 2.1
      fold increase in ACLP levels released into medium. Aortic carboxypeptidase-like
      protein overexpression did not inhibit differentiation in standard dishes. In
      collagen I-coated dishes compared with standard dishes, control preadipocytes,
      when induced to differentiate, exhibited the same increase in triacylglycerol
      accumulation, but showed a significantly higher induction of fatty acid synthase
      (1.6-fold more), peroxisome proliferator-activated receptor gamma (1.4-fold
      more), and CCAAT/enhancer-binding protein alpha (1.4-fold more). Aortic
      carboxypeptidase-like protein overexpression significantly reduced this enhanced
      induction of fatty acid synthase, peroxisome proliferator-activated receptor
      gamma, and CCAAT/enhancer-binding protein alpha by 65%, 59%, and 66%,
      respectively, but had no effect on the accumulation of triacylglycerol during
      differentiation. Finally, studies on proadipogenic insulin signaling in ACLP
      overexpressing preadipocytes demonstrated that insulin-stimulated Akt
      phosphorylation was significantly decreased by 27% in cells cultured in collagen
      I-coated dishes vs standard dishes. Our data suggest that ACLP inhibits certain
      aspects of 3T3-L1 adipogenesis in a collagen I-rich environment.

PMID- 20817215
TI  - Synthesis of 3-fluoro-6-S-(2-S-pyridyl) nucleosides as potential lead cytostatic
      agents.
AB  - The 3-deoxy-3-fluoro-6-S-(2-S-pyridyl)-6-thio-beta-D-glucopyranosyl nucleoside
      analogs 7 were prepared via two facile synthetic routes. Their precursors, 3
      fluoro-6-thio-glucopyranosyl nucleosides 5a-e, were obtained by the sequence of
      deacetylation of 3-deoxy-3-fluoro-beta-D-glucopyranosyl nucleosides 2a-e,
      selective tosylation of the primary OH of 3 and finally treatment with potassium
      thioacetate. The desired thiolpyridine protected analogs 7a-c,f,g were obtained
      by the sequence of deacetylation of 5a-c followed by thiopyridinylation and/or
      condensation of the corresponding heterocyclic bases with the newly synthesized
      peracetylated 6-S-(2-S-pyridyl) sugar precursor 13, which was obtained via a
      novel synthetic route from glycosyl donor 12. None of the compounds 6 and 7
      showed antiviral activity, but the 5-fluorouracil derivative 7c and particularly
      the uracil derivative 7b were endowed with an interesting and selective
      cytostatic action against a variety of murine and human tumor cell cultures.

PMID- 20817216
TI  - Synthesis of the natural enantiomer of neplanocin B.
AB  - (-)-Neplanocin B, the natural isomer of a component of the neplanocin family was
      diasteroselectively synthesized from 2,3-O-isopropylidene-D-1,4-ribonolactone.
      However, when evaluated against several DNA and RNA viruses in cell culture
      experiments, it did not show any antiviral activity.

PMID- 20817217
TI  - [Solitary fibrous tumor of the meninges in the olfactory sulcus].

PMID- 20817218
TI  - Comparative estimation of 232Th and stable Ce (III) toxicity and detoxification
      pathways in freshwater alga Chlorella vulgaris.
AB  - The impacts of radiological and chemical toxicity from naturally occurring
      radionuclides are discussed in the context of protecting freshwater ecosystems
      from radiation exposure. The present study aimed to determine the toxicity of
      (232)Th and it stable chemical analogue Ce to the green alga Chlorella vulgaris
      Beijerinck (thermophilic strain). Parameters of the regression equation for the
      concentration-effect relationship and concomitant Effective concentration (50%),
      EC(50), showed that (232)Th was more toxic to chlorella after a 24-h exposure
      than Ce. However, the No-observable-effect concentration (NOEC) and Lowest
      observable-effect concentration (LOEC) for (232)Th were approximately equal to
      those for Ce. NOEC, LOEC and EC(50) for (232)Th were 1.6 MUM, 2.2 MUM and 15.4
      respectively. Those for Ce were 1.8, 2.1 and 35.7 MUM respectively. Consideration
      of the results obtained suggests differences in the main detoxification pathways
      of (232)Th and Ce (III). It was found that 0.02 mM caffeine (used as DNA
      metabolism disturbance reagent) has no effect on Ce toxic action, but 0.02 mM BSO
      (as a selective inhibitor of gamma-ECS, a glutathione biosynthetic pathway
      enzyme) enhanced it. In contrast, 0.02 mM caffeine significantly increased the
      toxic action of (232)Th, but 0.02 mM BSO has no effect on it. The peculiarities
      mentioned were suggested to be caused by differences in the physicochemical
      properties of the elements. The combined potential detrimental effect of (232)Th
      acting both as a radiation source (alpha-, beta- and gamma-emitter) and a
      chemically toxic element is discussed.

PMID- 20817219
TI  - Trapping of BTX compounds by SiO2, Ag-SiO2, Cu-SiO2, and Fe-SiO2 porous
      substrates.
AB  - Adsorption isotherms of BTX aromatic hydrocarbons (benzene, toluene, and p
      xylene) on pristine (SiO2) and metal-doped (Ag-SiO2, Cu-SiO2 and Fe-SiO2)
      mesoporous and microporous substrates were measured and interpreted. These
      adsorbents were synthesized by the sol-gel procedure and their BTX sorption
      isotherms were obtained by the gas chromatographic technique (GC) at several
      temperatures in the range 423-593 K. The uptake amount of these hydrocarbon
      adsorptives on SiO2, Ag-SiO2, Cu-SiO2 and Fe-SiO2 mesoporous and microporous
      substrates was temperature-dependent. Additionally, the interaction of BTX
      molecules with the pore walls was evaluated by means of the corresponding
      isosteric heat of adsorption (qst), which was found to follow the next increasing
      sequence: qst (benzene)<qst (toluene)<qst (p-xylene). In general, the isosteric
      heat of adsorption of aromatic BTX compounds on microporous silica depicted an
      increasing tendency when the amount adsorbed was raised. This was a consequence
      of the existence of cohesive interactions (adsorbate-adsorbate) besides of the
      adhesive ones (adsorbate-adsorbent). The inclusion of silver or iron atoms within
      the SiO2 structure leads to an increased adsorbed amount of BTX molecules on the
      solid surface if compared with the Cu-SiO2 adsorbent. The adsorption of benzene,
      but not of toluene and p-xylene, molecules on pristine SiO2 is facilitated by the
      pore size of this substrate since this is the highest of all materials.

PMID- 20817220
TI  - Constructing naive Bayesian classifiers for veterinary medicine: a case study in
      the clinical diagnosis of classical swine fever.
AB  - For diseases of which the clinical diagnosis is uncertain, naive Bayesian
      classifiers can be of assistance to the veterinary practitioner. These simple
      probabilistic models have proven to be very powerful for solving classification
      problems in a variety of domains, but are not yet widely applied within the
      veterinary domain. In this paper, naive Bayesian classifiers and methods for
      their construction are reviewed. We demonstrate how to construct full and
      selective classifiers from a data set and how to build such classifiers from
      information in the literature. As a case study, naive Bayesian classifiers to
      discriminate between classical swine fever (CSF)-infected and non-infected pig
      herds were constructed from data collected during the 1997/1998 CSF epidemic in
      the Netherlands. The resulting classifiers were studied in terms of their
      accuracy and compared with the optimally efficient diagnostic rule that was
      reported earlier by Elbers et al. (2002). The classifiers were found to have
      accuracies within the range of 67-70% and performed comparable to or even better
      than the diagnostic rule on the available data. In contrast with the diagnostic
      rule, the classifiers had the advantage of taking both the presence and the
      absence of particular clinical signs into account, which resulted in more
      discriminative power. These results indicate that naive Bayesian classifiers are
      promising tools for solving diagnostic problems in the veterinary field.

PMID- 20817221
TI  - Thoron (220Rn) decay products removal in poorly ventilated environments using
      unipolar ionizers: dosimetric implications.
AB  - Ionizers are proven to be effective in reducing the activity concentration of
      radon/thoron decay products in workplace environments. However, limited studies
      have been conducted on understanding the mechanism of removal and the related
      size dependency. This study demonstrates the feasibility of reducing the activity
      concentrations in small chambers and in room environments up to a factor of about
      7. Field experiments in an uncontrolled ventilation area such as a thorium
      oxalate storage shed have also shown promising results with a possible
      concentration reduction by a factor of 4. However, these reductions have been
      necessarily associated with an increase (3-5 times) in the unattached fraction of
      the decay products which is a significant contributor to the lung dose. Owing to
      this, aspersions have been cast on the capability of the ionizers in reducing the
      effective dose. An attempt has been made here to estimate the effective doses
      over a wide range of parameters such as the initial unattached fraction, activity
      reduction ratio and the change in the unattached fraction, which get altered due
      to the use of ionizers. The study proves that for realistically achievable
      activity reduction ratios of about 3-5 with the employment of ionizers, the
      inhalation dose in workplace environments can be reduced by a factor of at least
      4, as indicated by model calculations.

PMID- 20817222
TI  - The importance of biomass net uptake for a trace metal budget in a forest stand
      in north-eastern France.
AB  - The trace metal (TM: Cd, Cu, Ni, Pb and Zn) budget (stocks and annual fluxes) was
      evaluated in a forest stand (silver fir, Abies alba Miller) in north-eastern
      France. Trace metal concentrations were measured in different tree compartments
      in order to assess TM partitioning and dynamics in the trees. Inputs included
      bulk deposition, estimated dry deposition and weathering. Outputs were leaching
      and biomass exportation. Atmospheric deposition was the main input flux. The
      estimated dry deposition accounted for about 40% of the total trace metal
      deposition. The relative importance of leaching (estimated by a lumped parameter
      water balance model, BILJOU) and net biomass uptake (harvesting) for ecosystem
      exportation depended on the element. Trace metal distribution between tree
      compartments (stem wood and bark, branches and needles) indicated that Pb was
      mainly stored in the stem, whereas Zn and Ni, and to a lesser extent Cd and Cu,
      were translocated to aerial parts of the trees and cycled in the ecosystem. For
      Zn and Ni, leaching was the main output flux (>95% of the total output) and the
      plot budget (input-output) was negative, whereas for Pb the biomass net
      exportation represented 60% of the outputs and the budget was balanced. Cadmium
      and Cu had intermediate behaviours, with 18% and 30% of the total output relative
      to biomass exportation, respectively, and the budgets were negative. The net
      uptake by biomass was particularly important for Pb budgets, less so for Cd and
      Cu and not very important for Zn and Ni in such forest stands.

PMID- 20817223
TI  - [Subperiostal orbital hemorrhage induced by effort for vomiting].
AB  - Subperiostal orbital hemorrhage is a rare condition. It usually occurs as a
      result of trauma or because of a vascular disorder. We present a case of
      subperiostal orbital hemorrhage induced by effort for vomiting. CASE: A 41-year
      old pregnant patient (30 weeks of amenorrhea), with no prior history, was
      referred to the ENT emergency by her gynecologist for unilateral ptosis and
      proptosis secondary to efforts for vomiting. Clinical examination and CT scanner
      showed a subperiostal hematoma of the orbital roof. The hematoma resolved in ten
      days without sequels, under simple surveillance. DISCUSSION: Non-traumatic
      subperiostal orbital hemorrhage remains rare. Clinical examination and orbital CT
      scan allow making the diagnosis. If the optic nerve is not compressed, clinical
      surveillance during hematoma resorption is sufficient.

PMID- 20817224
TI  - [Xanthogranuloma of the parotid gland in adults].
AB  - Juvenile xanthogranuloma (JXG) is a cutaneous non-Langerhans cell histiocytosis
      affecting infants. We report the first case of JXG in the parotid gland of an
      adult. CLINICAL CASE: A 52 year-old man consulted for a painful swelling of the
      left parotid region, progressively increasing. On physical examination, the mass
      was 4 cm in diameter. A second 1.5 cm diameter tumor was found in the right
      parotid region. MRI revealed masses with heterogeneous hypodense on T1-weighted
      images and with hyper dense on T2 weighted images associated with heterogeneous
      enhancement after gadolinium injection. The superficial and deep lobes of the
      parotid gland were involved. Per-operative left-side exploration revealed a
      lipomatous degeneration of the parotid gland and facial nerve. A lower polar
      parotidectomy was performed. The histological examination identified a parotid
      xanthogranuloma. DISCUSSION: The JXG is usually revealed by cutaneous lesions. In
      fact, the morphological, immunohistochemical, and ultrastructural features of
      this affection lead to its diagnosis. Extra-cutaneous localizations are less
      frequent. The differential diagnosis is X histiocytosis.

PMID- 20817225
TI  - Postoperative radiotherapy use and patterns of care analysis for node positive or
      parametria positive cervical cancer.
AB  - OBJECTIVE: The objective of this study is to perform a patterns of care analysis
      for post-hysterectomy patients with node positive (LN+) or parametria positive
      cervical cancer. METHODS: A retrospective analysis was conducted utilizing the
      Surveillance, Epidemiology and End Results (SEER) Program from 1973 to 2006. We
      identified 2247 women with cervical carcinoma who had undergone hysterectomy and
      were found to have LN+ and/or positive parametria. RESULTS: Of the 2247
      identified, 80.1% (1800) received postoperative radiotherapy (RT) while 19.9%
      (447) did not. Of those receiving RT, a significantly greater proportion had
      worse risk factors including higher clinical stage, and nodal bulk yet cause
      specific survival (CSS) was equivalent between the two groups. RT utilization has
      increased over time from 67.2% in the cohort analyzed from 1973 to 1982 to 81.8%
      in the cohort analyzed from 2004 to 2006 (p = 0.0003). Blacks had worse CSS than
      whites (HR 1.35, 95% CI [1.05, 1.75]; p = 0.02). The proportion of those
      receiving RT was lower in blacks than whites (74.7% vs. 80.5%; p = 0.0358). From
      1973 to 1982, 87.5% of blacks received RT while 62% of whites received RT (p =
      0.0463). From 2004 to 2006, 64.4% of blacks received RT while 83.0% of whites
      received RT (p = 0.0024). CONCLUSIONS: Despite randomized data supporting the use
      of postoperative concurrent chemoradiotherapy for LN+ or parametria positive
      cervical cancer, the proportion of blacks not receiving RT is increasing over
      time. This is the largest patterns of care analysis to date of RT in patients
      with LN+ and/or parametria positive cervical cancer.

PMID- 20817227
TI  - A 2-year prospective study assessing the emotional, sexual, and quality of life
      concerns of women undergoing radical trachelectomy versus radical hysterectomy
      for treatment of early-stage cervical cancer.
AB  - OBJECTIVE: To prospectively assess and describe the emotional, sexual, and QOL
      concerns of women with early-stage cervical cancer undergoing radical surgery.
      METHODS: Seventy-one women who were consented for radical trachelectomy (RT) or
      radical hysterectomy (RH) were enrolled preoperatively in this 2-year study; 52
      women (33 RT; 19 RH) were actively followed. Patients completed self-report
      surveys composed of 4 empirical measures in addition to exploratory items. Data
      analyses for the 2 years of prospective data are presented. RESULTS: At
      preoperative assessment, women choosing RH reported greater concern about cancer
      recurrence (x=7.27 [scale from 0 to 10]) than women choosing RT (x=5.66)
      (P=0.008). Forty-eight percent undergoing RH compared to 8.6% undergoing RT
      reported having adequate "time to complete childbearing" (P<0.001). Both groups
      demonstrated scores suggestive of depression (based on the CES-D scale) and
      distress (based on the IES scale) preoperatively; over time, however, CES-D and
      IES scores generally improved. Scores on the Female Sexual Functioning Inventory
      (FSFI) for the total sample were below the mean cut-off (26.55), suggestive of
      sexual dysfunction; however, the means increased from 16.79 preoperatively to
      23.78 by 12 months and 22.20 at 24 months. CONCLUSION: Measurements of mood,
      distress, sexual function, and QOL did not differ significantly by surgical type,
      and instead reflect the challenges faced by young cervical cancer patients
      treated by RT or RH without adjuvant treatment. Points of vulnerability were
      identified in which patients may benefit from preoperative consultation or
      immediate postoperative support. Overall, patients improved during the first
      year, reaching a plateau between Year-1 and Year-2, which may reflect a new level
      of functioning in survivorship.

PMID- 20817226
TI  - MTHFR polymorphisms in relation to ovarian cancer risk.
AB  - OBJECTIVE: Folate has been hypothesized to influence carcinogenesis due to its
      dual role in DNA methylation, which regulates gene expression, and synthesis of
      purine and thymidylate, which is vital for DNA repair. Thus, we examined ovarian
      cancer risk in relation to two functional polymorphisms (C677T and A1298C) in the
      MTHFR gene. METHODS: We genotyped the C677T (rs1801133) and A1298C (rs1801131)
      MTHFR polymorphisms in 1642 cases and 2068 controls from three studies, the New
      England Case Control Study (NEC), Nurses' Health Study (NHS), and Mayo Clinic
      Ovarian Cancer Case Control Study (MAY). RESULTS: Overall, we observed no
      association between either SNP and ovarian cancer risk (pooled C677T
      p(trend)=0.59 and A1298C p(trend)=0.58). Significant associations (C677T
      p(trend)=0.001, A1298C p(trend)=0.02) between these MTHFR SNPs and serous ovarian
      cancer risk were observed in the NEC study, but were not replicated in the NHS
      and MAY studies. CONCLUSIONS: MTHFR SNPs C677T and A1298C are not associated with
      ovarian cancer risk. Our results highlight the need for validation of genetic
      findings.

PMID- 20817228
TI  - Long-term analysis of clinical outcome and complications in locally advanced
      cervical cancer patients administered concomitant chemoradiation followed by
      radical surgery.
AB  - OBJECTIVE: Preoperative chemoradiation (CT/RT) has been shown to achieve
      encouraging results in terms of clinical outcome in locally advanced cervical
      cancer (LACC). The study aims at analyzing the long-term results of this
      multimodal approach in a single institution series of 184 cases. METHODS:
      Patients underwent whole pelvic irradiation combined with cisplatin and 5
      fluorouracil. After evaluation of clinical response, patients were triaged to
      surgery. Surgical morbidity was classified according to Chassagne grading system.
      Univariate and multivariate analyses were used to assess the prognostic and
      predictive role of clinicopathological parameters. RESULTS: Clinical response was
      observed in 96.1% of cases. A total of 174 cases were submitted to radical
      surgery: 124 patients (71.3%) showed complete/microscopic pathological response.
      In multivariate analysis, clinical response, stage of disease, and histotype
      predicted response to CT/RT. With a median follow-up of 58 months, recurrence and
      death of disease were observed in 42 and 40 patients, respectively. The 5-year
      DFS was 75.5%, while the 5-year OS was 77.4%. Patients with no residual disease
      showed a significant longer DFS than patients with microscopic (p value =
      0.0128), and macroscopic (p value = 0.0001) residual tumor after treatment. In
      multivariate analysis, residual tumor and stage of disease were the two most
      relevant prognostic factors for DFS and OS. As far as long-term toxicity is
      concerned, 8 out of 22 complications were grade 3/4. CONCLUSION: Preoperative
      CT/RT is worth further investigation in LACC patients, providing encouraging
      survival outcomes and a favourable long-term toxicity profile.

PMID- 20817229
TI  - Neurogenic orthostatic hypotension of Parkinson's disease: what exploration for
      what treatment?
AB  - The aim of this short review is to illustrate, using orthostatic hypotension as
      an example, the clinical problems related to autonomic features in Parkinson's
      disease. Orthostatic hypotension is frequently encountered in Parkinson's disease
      and its diagnosis remains manometric (a fall of at least 20 and/or 10 mmHg in
      standing blood pressure). It is often associated with supine hypertension to be
      taken into account before prescribing. To distinguish between the role of disease
      and of drugs (not only antiparkinsonian drugs), a simple clinical test of
      autonomic nervous system activity (deep breathing test and standing test with
      measurement of 30/15 ratio) can be used. When diagnosis with multisystem atrophy
      is discussed, cardiac [123I]-metaiodobenzylguanidine (MIBG) scintigraphy is of
      value showing in Parkinson's disease a decreased uptake of the
      radiopharmaceutical indicating postganglionic sympathetic denervation. Concerning
      treatment, nonpharmacological methods have to be systematically used since no
      drug has been specifically evaluated for the treatment of orthostatic hypotension
      of Parkinson's disease.

PMID- 20817230
TI  - ["Red flags": when to be alerted and how to explore?].
AB  - The diagnosis of Parkinson's disease (PD) requires ruling out other causes of
      parkinsonism. Among various "other" causes of parkinsonism, neurodegenerative
      causes or "atypical parkinsonism" are the most difficult to diagnose. Most common
      diseases are "synucleinopathies": multiple system atrophy and dementia with Lewy
      bodies and "tauopathies": progressive supranuclear palsy and corticobasal
      degeneration. Unexpected or atypical signs and symptoms for PD, also called "red
      flags" along with absent or poor or short-lived levodopa response may be a clue
      for the diagnosis. Some tests may also support the diagnosis, among them,
      structural (MRI) and functional brain imaging, autonomic function tests and
      urodynamics, oculographic recordings and neuropsychological work-up, are the most
      useful.

PMID- 20817231
TI  - Emerging parkinsonian phenotypes.
AB  - There is no unique way to define Parkinson's disease (PD) clinically. "Classical
      parkinsonian features" can be found not only in sporadic idiopathic PD patients,
      but also in other parkinsonian disorders, such as genetic forms associated with
      mutations in PARK or in other genes. The present review will describe the
      parkinsonian phenotypes emerging from the new Mendelian genes which have been
      linked to PD (such as PARK9 and PARK14), the associated dystonia-parkinsonism
      disorders (such as the syndromes of neurodegeneration with brain iron
      accumulation) and the emerging data on heterozygous variants of genes which could
      influence the risk to develop PD and the PD phenotypes (like PD associated with
      glucose cerebrosidase mutations).

PMID- 20817233
TI  - Ecological transition from natural forest to tea plantations: effect on the
      dynamics of malaria vectors in the highlands of Cameroon.
AB  - From October 2002 to September 2003, an entomological survey was carried out in a
      rural forested fringed village in the highlands of Mount Cameroon region to
      determine the temporal dynamics of the anopheline population and the intensity of
      malaria transmission. A total of 2387 Anopheles spp. were collected, with A.
      funestus predominating (59.9%), followed by A. hancocki (24.4%) and A. gambiae
      s.l. (15.7%). Considerable differences were observed in the nocturnal biting
      cycles of parous mosquitoes, with peak activity in the latter part of the night.
      PCR revealed that all specimens of the A. funestus group were A. funestus s.s.
      and all specimens from the A. gambiae complex were A. gambiae s.s. of the S
      molecular form. Plasmodium falciparum sporozoite rates of 17.3% and 8.5% were
      recorded for A. funestus and A. hancocki, respectively, with an anthropophilic
      rate of 96.3%. A strong positive correlation (r=0.996) was found between the
      human-biting rate and the entomological inoculation rate (EIR). Malaria
      transmission was very high and perennial, with an estimated annual EIR of 460.1
      infective bites per person per year. These results confirm that in high
      agricultural activity areas, A. funestus can be by far the major malaria vector
      responsible for malaria transmission.

PMID- 20817232
TI  - [Parkinson's disease: Role of genetic and environment factors. Involvement in
      everyday clinical practice].
AB  - Genetics and exposure to toxins constitute the main determinants in the onset of
      Parkinson's disease (PD). At least, 13 loci and nine genes involved in familial
      and sporadic forms have been described. A significant association between
      occupational exposure to pesticides (especially insecticides) and PD has been
      confirmed recently with rare cases even being recognized as occupational disease.
      We develop in this paper a practical approach for such situations where a common
      genetic or toxic origin is suggested. Such an approach can be applied very
      broadly using case by case study then further analysis in a specialized center of
      reference in the field of genetics or occupational diseases and the environment.
      A pedigree needs to be drawn to evaluate a potential genetic factor with, if
      possible, the examination of various family members. Depending on the mode of
      inheritance, age of disease onset and phenotypic expression, genetic analysis
      will be carried out (mainly the study of parkin gene for recessive transmission
      and LRRK2 gene for dominant transmission). The evaluation of a toxic factor is
      more difficult because its direct involvement may not always be defined with
      certainty, the collection of information is more complex (product list, causal
      relationship, protection system used...). The course of action will identify the
      existence of a potential risk factor particularly in patients at risk (farmers,
      workers in a factory using heavy metals) by considering secondary specialized
      consultation with the occupational physician or pathology consultation work for
      possible development of a procedure for recognition of occupational disease.

PMID- 20817234
TI  - Partial bile duct ligation in mice: a novel model of acute cholestasis.
AB  - BACKGROUND: The standard model for research in cholestasis is the total ligation
      of the bile duct (tBDL). Because this model causes severe hepatic injury in mice,
      we developed a novel model of cholestasis using a partial bile duct ligation
      (pBDL) and evaluate different mechanisms of injury. METHODS: Male C57Bl/6 mice
      were subjected to sham operation, tBDL, or pBDL. Blood from tail veins was taken
      repeatedly until day 14 after surgery to assess markers of tissue injury
      (aspartate aminotransferase [AST]) and cholestasis (bilirubin, alkaline
      phosphatase [AP]). Also, liver samples were obtained at various time points to
      determine the histologic injury (hematoxylin and eosin) and tissue repair (Ki67).
      In addition, the biliary pressure and serum bile acids were evaluated as
      potential mechanisms of injury. RESULTS: Both models of cholestasis were equal in
      terms of bilirubin, AST, and AP serum levels during the first week of the
      experiment. Although these parameters remained constantly elevated thereafter in
      the tBDL model, all parameters normalized within the second week after pBDL.
      Moreover, pBDL resulted in significantly less necrosis formation (P = .001) and
      consequent hepatocyte proliferation (P= .01). Most important, serum bile acid
      levels (P = .04) and biliary pressures (P = .02) were significantly lower after
      pBDL than after tBDL and were the best predictors for hepatic necrosis formation.
      CONCLUSION: We established a model of acute cholestasis, which is ideal for
      research in resolved acute cholestasis (eg, surgery for Klatskin tumors).
      Moreover, biliary pressure and toxic bile acid serum levels may be better
      predictors of cholestatic liver injury than standard laboratory parameters.

PMID- 20817235
TI  - Portal vein embolization induces more liver regeneration than portal vein
      ligation in a standardized rabbit model.
AB  - BACKGROUND: Portal vein ligation (PVL) and portal vein embolization (PVE) are
      used to induce hypertrophy of the future remnant liver before major liver
      resection. The aim of our study was to compare the hypertrophy response of the
      liver after PVL versus PVE in a rabbit model. METHODS: Twenty rabbits were
      divided into an embolization group (n = 10) and a ligation group (n = 10). Both
      groups were divided in 2 subgroups of 5 rabbits that were humanely killed after
      days 7 and 14. The portal vein branches to the 3 cranial liver lobes (80% of the
      liver) were occluded. Regeneration of the caudal liver lobe was measured using
      volumetry based on computed tomography on days 3, 7, 10, and 14.
      Immunohistochemistry for Ki-67 and RAM11 was performed to quantify proliferating
      cells and macrophages. In addition, tissue tumor necrosis factor-alpha and
      interleukin-6 were assessed. RESULTS: The caudal liver volume increased over time
      in both groups (P < .001), but this increase was greater after PVE than after PVL
      (P = .001) with a mean degree of hypertrophy of 15% +/- 4% and 20% +/- 2%,
      respectively. When comparing the groups on the separate time points, a difference
      was found on days 10 and 14 (P = .008 and P = .016, respectively). These data
      were confirmed by Ki-67 staining, which showed a greater number of proliferating
      hepatocytes on day 7 after embolization (P = .016). Cytokine analysis of liver
      tissue did not show significant differences between the ligation and embolization
      groups on days 7 and 14. CONCLUSION: PVE is superior to PVL in terms of the
      extent of the hypertrophy response in this rabbit model.

PMID- 20817236
TI  - Assessing romantic competence among older adolescents.
AB  - Davila and colleagues (Davila et al., 2009) developed the Romantic Competence
      Interview to capture the potential for romantic competence during early
      adolescence. Considering that at later stages of adolescence the majority are
      likely to be involved in some kind of romantic relationship, the current paper
      adapts, extends, and examines the concept of romantic competence among older
      adolescents. Seventy two Israeli adolescent girls (mean age 17.17 years) were
      given a revised version of the RCI along with measures of quality of relationship
      with romantic partners and parents, and quality of parental marital satisfaction.
      Mothers were also interviewed and were asked to talk about their attitudes toward
      daughters' romantic behavior. Results showed that RCI scales were reliably coded
      and exhibited good construct validity. The meaning and expression of romantic
      competence among older adolescents is conceptualized and discussed within the
      framework of developmental and agency perspectives.

PMID- 20817237
TI  - Allatotropin expression during the development of the fourth instar larvae of the
      kissing-bug Triatoma infestans (Klug).
AB  - Allatotropin (AT) is a neuropeptide originally isolated from the brain of Manduca
      sexta and then characterized in several insect species. It acts as a
      neurohormone, as well as a neuromodulator. While it was primarily characterized
      on the basis of its ability to stimulate the secretion of juvenile hormones, it
      was also found that it acts as a cardioaccelerator and myostimulator. The
      presence of AT in IV instar larvae of T. infestans was previously described at
      the level of the Malpighian tubules. In the present study we report the presence
      of the peptide at the level of the brain, retrocerebral complex, as well as in
      the anterior midgut and aorta. The presence of AT at the corpora allata suggests
      that the peptide is acting on the gland during the first days of the moulting
      cycle. Neural processes at the level of the aorta and the anterior midgut
      suggests that, like in adults, the hormone is acting as a cardioaccelerator and
      myostimulator. The peptide was also found in open-type cells of the midgut.
      Finally the presence of allatotropic neurons in the optical lobe of the brain
      suggests that as in other species, the peptide is related with the control of
      circadian rhythms.

PMID- 20817238
TI  - Effects of recombinant adeno-associated viral vectors on angiopoiesis and
      osteogenesis in cultured rabbit bone marrow stem cells via co-expressing hVEGF
      and hBMP genes: a preliminary study in vitro.
AB  - OBJECTIVE: VEGF and BMP play important roles in angiogenesis and osteogenesis.
      Combining these two factors may be a promising therapeutic strategy for avascular
      necrosis of the femoral head (ANFH). METHODS: Rabbit bone marrow-derived
      mesenchymal stem cells (BMSCs) were isolated and purified by density gradient
      centrifugation combined with attachment culture methods. The purity and
      characteristics of the BMSCs were detected by cell surface antigen
      identification. The best MOI of BMSCs transfected with rAAV was detected by
      fluorescent cell counting, and cell viability was determined by MTT assay.
      Expression of the genes of interest was detected by GFP gene expression, RT-PCR
      assay, and ELISA assay. The biological activities of VEGF and BMP were detected
      by angiogenic and osteogenic assays. RESULTS: The best MOI of BMSCs transfected
      with rAAV was 5 x 10(4)v.g./cell. Cell growth curves showed vigorous cell
      viability. Expressions of the GFP, VEGF165, and BMP(7) genes were detected 1 day
      post-transfection and peaked 14 days post-transfection. Expression of the genes
      of interest was sustained over 1 month. VEGF and BMP proteins secreted from BMSCs
      transfected with rAAV-hVEGF(165)-IRES-hBMP(7) enhanced angiogenesis and
      osteogenesis in vitro. CONCLUSION: Recombinant adeno-associated viral vectors co
      expressing the hVEGF(165) and hBMP(7) genes showed efficient gene expression
      ability. The VEGF(165) and BMP(7) proteins expressed from the vector have
      efficient biological activity in vitro.

PMID- 20817239
TI  - Distribution of NADPH-diaphorase activity in the central nervous system of the
      young and adult land snail Megalobulimus abbreviatus.
AB  - Nitric oxide (NO) is a gas produced through the action of nitric oxide synthase
      that acts as a neurotransmitter in the central nervous system (CNS) of adult
      gastropod mollusks. There are no known reports of the presence of NOS-containing
      neurons and glial cells in young and adult Megalobulimus abbreviatus. Therefore,
      NADPH-d histochemistry was employed to map the nitrergic distribution in the CNS
      of young and adult snails in an attempt to identify any transient enzymatic
      activity in the developing CNS. Reaction was observed in neurons and fibers in
      all CNS ganglia of both age groups, but in the pedal and cerebral ganglia,
      positive neurons were more intense than in other ganglia, forming clusters
      symmetrically located in both paired ganglia. However, neuronal NADPH-d activity
      in the mesocerebrum and pleural ganglia decreased from young to adult animals. In
      both age groups, positive glial cells were located beneath the ganglionic
      capsule, forming a network and surrounding the neuronal somata. The
      trophospongium of large and giant neurons was only visualized in young animals.
      Our results indicate the presence of a nitrergic signaling system in young and
      adult M. abbreviatus, and the probable involvement of glial cells in NO
      production.

PMID- 20817240
TI  - Bilateral eyestalk ablation of the blue swimmer crab, Portunus pelagicus,
      produces hypertrophy of the androgenic gland and an increase of cells producing
      insulin-like androgenic gland hormone.
AB  - The androgenic glands (AG) of male decapod crustaceans produce insulin-like
      androgenic gland (IAG) hormone that controls male sex differentiation, growth and
      behavior. Functions of the AG are inhibited by gonad-inhibiting hormone
      originating from X-organ-sinus gland complex in the eyestalk. The AG, and its
      interaction with the eyestalk, had not been studied in the blue swimmer crab,
      Portunus pelagicus, so we investigated the AG structure, and then changes of the
      AG and IAG-producing cells following eyestalk ablation. The AG of P. pelagicus is
      a small endrocrine organ ensheathed in a connective tissue and attached to the
      distal part of spermatic duct and ejaculatory bulb. The gland is composed of
      several lobules, each containing two major cell types. Type I cells are located
      near the periphery of each lobule, and distinguished as small globular cells of 5
      7 MUm in diameter, with nuclei containing mostly heterochromatin. Type II cells
      are 13-15 MUm in diameter, with nuclei containing mostly euchromatin and
      prominent nucleoli. Both cell types were immunoreactive with anti-IAG. Following
      bilateral eyestalk ablation, the AG underwent hypertrophy, and at day 8 had
      increased approximately 3-fold in size. The percentage of type I cells had
      increased more than twice compared with controls, while type II cells showed a
      corresponding decrease.

PMID- 20817241
TI  - Paradoxial changes in the expression of estrogen receptor alpha in breast cancer
      multicellular spheroids.
AB  - Multicellular spheroids are excellent models for the analysis of cancer behavior.
      Just like small avascular tumors, they present a marked zonal heterogeneity which
      influences gene expression and thus, growth and response to chemotherapy. In the
      present paper, we sought to analyze the effects of three-dimensional culture in
      the expression and distribution of estrogen receptor alpha. Using MCF-7 breast
      cancer cells, we found that multicellular spheroids in estrogen-containing medium
      presented a paradoxical regulation of estrogen receptor alpha, with a decrease in
      protein expression and a marked increase in mRNA steady-state levels.
      Immunohistochemistry showed that only sparse cells in the periphery of the
      spheroid expressed estrogen receptor, in sharp contrast with progesterone
      receptor, which was more extensively expressed and HIF-alpha, which was expressed
      in the central core of the spheroid. This could mean that both hypoxia and ERA
      activation by estrogen participate in the expression heterogeneity of this
      hormone receptor in breast cancer These results are important to considerate in
      the analysis and interpretation of immunohistochemistry of ERA and downstream
      targets in samples of solid tumors.

PMID- 20817242
TI  - Fine structure of the vomeronasal organ in the grass lizard, Takydromus
      tachydromoides.
AB  - The squamates are composed of many taxa, among which there is morphological
      variation in the vomeronasal organ (VNO). To elucidate the evolution of
      chemoreception in squamate reptiles, morphological data from the VNO from a
      variety of squamate species is required. In this study, the morphology of the VNO
      of the grass lizard Takydromus tachydromoides was examined using light and
      electron microscopy. The VNO consists of a pair of dome-shaped structures, which
      communicate with the oral cavity. There are no associated glandular structures.
      Microvilli are present on the apical surfaces of receptor cells in its sensory
      epithelium, as well as on supporting cells, and there are centrioles and ciliary
      precursor bodies on the dendrites. In addition to ciliated cells and basal cells
      in the non-sensory epithelium, there is a novel type of non-ciliated cell in T.
      tachydromoides. They have constricted apical cytoplasm and microvilli instead of
      cilia, and are sparsely distributed in the epithelium. Based on these results,
      the variation in the morphology of the VNO in scincomorpha, a representative
      squamate taxon, is discussed.

PMID- 20817243
TI  - Bacteriocyte-like cells harbour Wolbachia in the ovary of Drosophila melanogaster
      (Insecta, Diptera) and Zyginidia pullula (Insecta, Hemiptera).
AB  - Wolbachia is the most widespread bacterial endosymbiont in insects. It is
      responsible for a variety of reproductive alterations of the hosts. Wolbachia is
      transmitted through the germline from mother to offspring and, in rare cases,
      between individuals. This implies that acquired properties (through symbiosis
      with Wolbachia) can become heritable. We investigated the transovarial
      inheritance of Wolbachia in two phylogenetically distant insects, Drosophila
      melanogaster and Zyginidia pullula. We detected in both systems bacteriocyte-like
      cells, densely packed with Wolbachia endosymbionts, at the tip of the ovarioles.
      Bacteriocytes are cells specialized to harbour bacteria, typical of mutualistic
      insect symbiosis. Our observations of bacteriocyte-like cells harbouring
      Wolbachia in the ovary emphasize the plasticity of the female reproductive system
      of insects, which maintains its function while some cells are densely colonized
      by bacteria. In summary, there is evidence from different insects that bacteria
      which behave as parasites of reproduction are harboured by cells resembling
      bacteriocytes, which appear to mediate transmission of the bacteria to the
      progeny. It seems a valid hypothesis that the bacteriocyte-like cells that we
      observed are not the result of a co-evolution of host and symbiont, considering
      that Wolbachia is not an obligatory symbiont in Drosophila and Zyginidia.

PMID- 20817244
TI  - Ultrastructural and functional characterization of circulating hemocytes from
      Plutella xylostella larva: cell types and their role in phagocytosis.
AB  - The hemocytes of different types encountered in the diamondback moth Plutella
      xylostella larvae of each instar and the development of the differential
      hemocytes counts were herein presented. Hemocytes classes/populations
      characterized based on their affinity with fluorescent dye (acridine orange) and
      ultrastructural differences comprised the prohemcoytes (<10-16%), plasmatocytes
      (22-65%), granulocytes (25-72%), oenocytoids (<1-9%), and spherulocytes (<1%).
      Prohemcoytes were the smallest cells with a comparatively tremendous nucleus.
      Plasmatocytes and granulocytes occupied the main proportion of total cell
      numbers. Oenocytoids were in a most stable presence, i.e. rotund in a diameter of
      10 MUm and with a nucleus deviated from the central location; however, sometimes
      with two nuclei which were adjoining with each other. Spherulocytes were rare and
      only could be observed occasionally. Ultrastructural investigation revealed that
      hemocytes in the diamondback moth larvae were of the typical model as in the
      Lepidoptera insect larvae. It is interesting to find that the cell which could
      phagocytize bacteria in vitro was granulocyte, not the other types of hemocytes,
      although plasmatocyte was usually declared to participate in this reaction in
      various previous studies.

PMID- 20817245
TI  - Is sucrose an effective analgesic for newborn babies?

PMID- 20817246
TI  - Health-systems strengthening: current and future activities.

PMID- 20817247
TI  - Oral sucrose as an analgesic drug for procedural pain in newborn infants: a
      randomised controlled trial.
AB  - BACKGROUND: Many infants admitted to hospital undergo repeated invasive
      procedures. Oral sucrose is frequently given to relieve procedural pain in
      neonates on the basis of its effect on behavioural and physiological pain scores.
      We assessed whether sucrose administration reduces pain-specific brain and spinal
      cord activity after an acute noxious procedure in newborn infants. METHODS: In
      this double-blind, randomised controlled trial, 59 newborn infants at University
      College Hospital (London, UK) were randomly assigned to receive 0.5 mL 24%
      sucrose solution or 0.5 mL sterile water 2 min before undergoing a clinically
      required heel lance. Randomisation was by a computer-generated randomisation
      code, and researchers, clinicians, participants, and parents were masked to the
      identity of the solutions. The primary outcome was pain-specific brain activity
      evoked by one time-locked heel lance, recorded with electroencephalography and
      identified by principal component analysis. Secondary measures were baseline
      behavioural and physiological measures, observational pain scores (PIPP), and
      spinal nociceptive reflex withdrawal activity. Data were analysed per protocol.
      This study is registered, number ISRCTN78390996. FINDINGS: 29 infants were
      assigned to receive sucrose and 30 to sterilised water; 20 and 24 infants,
      respectively, were included in the analysis of the primary outcome measure.
      Nociceptive brain activity after the noxious heel lance did not differ
      significantly between infants who received sucrose and those who received sterile
      water (sucrose: mean 0.10, 95% CI 0.04-0.16; sterile water: mean 0.08, 0.04-0.12;
      p=0.46). No significant difference was recorded between the sucrose and sterile
      water groups in the magnitude or latency of the spinal nociceptive reflex
      withdrawal recorded from the biceps femoris of the stimulated leg. The PIPP score
      was significantly lower in infants given sucrose than in those given sterile
      water (mean 5.8, 95% CI 3.7-7.8 vs 8.5, 7.3-9.8; p=0.02) and significantly more
      infants had no change in facial expression after sucrose administration (seven of
      20 [35%] vs none of 24; p<0.0001). INTERPRETATION: Our data suggest that oral
      sucrose does not significantly affect activity in neonatal brain or spinal cord
      nociceptive circuits, and therefore might not be an effective analgesic drug. The
      ability of sucrose to reduce clinical observational scores after noxious events
      in newborn infants should not be interpreted as pain relief. FUNDING: Medical
      Research Council.

PMID- 20817248
TI  - Fine-tuning DNA/albumin polyelectrolyte interactions to produce the efficient
      transfection agent cBSA-147.
AB  - We present the preparation and isolation of different chemically modified BSA
      species with varying numbers of primary amino groups at the surface. Highly
      cationic albumin proteins with increased numbers of amino groups were achieved
      and complex formation with plasmid DNA was carefully investigated. We compare the
      transfection results, polyelectrolyte complexes morphologies with their impact on
      complex stabilities, cytotoxicities and DNA accessibility. This knowledge-driven
      approach led to the identification of the efficient non-viral DNA delivery agent
      cBSA-147, which showed high transfection efficacies and stability.

PMID- 20817249
TI  - Portable microcontact printing device for cell culture.
AB  - In this work, we developed a portable device to perform microcontact printing in
      a safety cabinet for cell culture. The device was designed to be small and non
      bulky, easy to sterilize, while not requiring the use of electricity, and which
      requires very little manual handling. Moreover, the portable microcontact printer
      is reproducibly fabricated with a rapid prototyping system, and allows for the
      easy micropatterning of biomolecules with a resolution ranging from 20 to 500
      MUm. This opens new horizons in the direct and simple micropatterning of culture
      dishes and the mimicking and biofabrication of complex architectures of tissues.

PMID- 20817250
TI  - Beam localization in HIFU temperature measurements using thermocouples, with
      application to cooling by large blood vessels.
AB  - Experimental studies of thermal effects in high-intensity focused ultrasound
      (HIFU) procedures are often performed with the aid of fine wire thermocouples
      positioned within tissue phantoms. Thermocouple measurements are subject to
      several types of error which must be accounted for before reliable inferences can
      be made on the basis of the measurements. Thermocouple artifact due to viscous
      heating is one source of error. A second is the uncertainty regarding the
      position of the beam relative to the target location or the thermocouple
      junction, due to the error in positioning the beam at the junction. This paper
      presents a method for determining the location of the beam relative to a fixed
      pair of thermocouples. The localization technique reduces the uncertainty
      introduced by positioning errors associated with very narrow HIFU beams. The
      technique is presented in the context of an investigation into the effect of
      blood flow through large vessels on the efficacy of HIFU procedures targeted near
      the vessel. Application of the beam localization method allowed conclusions
      regarding the effects of blood flow to be drawn from previously inconclusive
      (because of localization uncertainties) data. Comparison of the position-adjusted
      transient temperature profiles for flow rates of 0 and 400ml/min showed that
      blood flow can reduce temperature elevations by more than 10%, when the HIFU
      focus is within a 2mm distance from the vessel wall. At acoustic power levels of
      17.3 and 24.8W there is a 20- to 70-fold decrease in thermal dose due to the
      convective cooling effect of blood flow, implying a shrinkage in lesion size. The
      beam-localization technique also revealed the level of thermocouple artifact as a
      function of sonication time, providing investigators with an indication of the
      quality of thermocouple data for a given exposure time. The maximum artifact was
      found to be double the measured temperature rise, during initial few seconds of
      sonication.

PMID- 20817252
TI  - Gr-1+ cells, but not neutrophils, limit virus replication and lesion development
      following flank infection of mice with herpes simplex virus type-1.
AB  - Neutrophils are prominent in epidermal and dermal layers of human herpetic
      lesions and are rapidly recruited into the skin follow epidermal abrasion and
      infection of mice with herpes simplex virus type-1 (HSV-1). Herein, we
      demonstrate that early production of neutrophil-attracting chemokines KC/MIP-2 is
      associated with transient recruitment of neutrophils into the skin of HSV-1
      infected mice in temporal association with the development of herpetic lesions.
      Treatment of HSV-1-infected mice with a Ly6G-specific mAb induced systemic
      neutropenia, but surprisingly did not alter virus replication or lesion
      development. In contrast, depletion of Gr-1(+) cells with mAb RB6-8C5 led to
      enhanced virus growth and lesion severity. Thus, while neutrophils are prominent
      in zosteriform lesions of HSV-1-infected mice, they do not appear to play a major
      role in controlling virus replication or lesion development and/or healing. In
      contrast, Gr-1(+) cells limit both virus replication and lesion development in
      the zosteriform model.

PMID- 20817251
TI  - Spontaneous and electrically evoked Ca2+ transients in cardiomyocytes of the rat
      pulmonary vein.
AB  - The pulmonary vein is surrounded by an external sleeve of cardiomyocytes that are
      widely recognised to play an important role in atrial fibrillation. While
      intracellular Ca(2+) is thought to influence the electrical activity of
      cardiomyocytes, there have been relatively few studies examining Ca(2+)
      signalling in these cells. Therefore, using fluo-4 and fluorescence imaging
      microscopy, we have investigated Ca(2+) signalling in an intact section of the
      rat pulmonary vein. Under resting conditions cardiomyocytes displayed spontaneous
      Ca(2+) transients, which were variable in amplitude and had a frequency of 1.6+/
      0.03Hz. The Ca(2+) transients were asynchronous amongst neighbouring
      cardiomyocytes and tended to propagate throughout the cell as a wave. Removing
      extracellular Ca(2+) produced a slight reduction in the amplitude and frequency
      of the spontaneous Ca(2+) transients; however, ryanodine (20MUM) had a much
      greater effect on the amplitude and reduced the frequency by 94+/-2%. Blocking
      IP(3) receptors with 2-aminoethoxydiphenyl borate (20MUM) also reduced the
      amplitude and frequency (by 73+/-11%) of these events, indicating the importance
      of Ca(2+) release from the SR. Electrical field stimulation of the pulmonary vein
      produced Ca(2+) transients in cardiomyocytes that were significantly reduced by
      either voltage-gated Ca(2+) channel blockers or ryanodine.

PMID- 20817253
TI  - Mineral recovery from inland reverse osmosis concentrate using isothermal
      evaporation.
AB  - Mineral recovery from reverse osmosis (RO) concentrate after concentration by a
      secondary sea water-type RO system with lime-soda pretreatment was the focus of
      this study. Lime-soda pretreatment removed Ca, Mg and Si allowing for the
      application of sea water-type RO resulting in a concentrate composed of sodium,
      potassium, sulfate and chloride. The overall objective was reduction in
      concentrate volume that will require disposal by evaporation while producing by
      products with potential resale value. Thermodynamic phase equilibrium
      calculations using Pitzer's correlations for 25  degrees C, accurately predicted
      the solubility and evaporation path of the sodium sulfate minerals as potential
      by-products. Bench-scale evaporation experiments verified the model predictions
      and indicated that 81-88% of the sodium sulfate by-products were Na(2)SO(4).

PMID- 20817254
TI  - Prevention of cytogenetic, histochemical and biochemical alterations in
      Oreochromis niloticus by dietary supplement of sorbent materials.
AB  - The current study was conducted to evaluate the ability of Egyptian bentonite
      (EB) and montmorillonite (EM) for the prevention of genotoxicity, histochemical
      and biochemical changes induced by aflatoxin B(1) (AFB(1)) using the micronucleus
      (MN) assay, chromosomal aberrations and DNA fragmentation analysis in Tilapia
      fish. Six groups of fish were treated for 3 weeks and included the control group,
      AFB(1)-treated group and the groups treated with EB or EM alone or in combination
      with AFB(1). At the end of experiment period, blood samples were collected for
      MN, testosterone and biochemical assays. Chromosomal aberrations were determined
      in kidney tissues, DNA fragmentation test was determined in liver and testis,
      whereas histochemical study was carried out on liver, testis and gills. The
      results indicated that a significant decrease in total protein, albumin,
      globulin, testosterone and DNA content in liver, gills and testis accompanied
      with a significant increase in number of micronucleated erythrocytes (MnRBCs),
      total chromosomal aberrations in kidney and DNA fragmentation in testis and liver
      of fish received AFB(1) alone. Fish treated with EB or EM alone were comparable
      to the control regarding the biochemical parameters except testosterone in EB
      treated group which was significantly decreased. Both clays did not induce any
      significant differences in number of MnRBCs, chromosomal aberrations in the
      kidney, DNA fragmentation in testis, but not in liver of EB-treated group. The
      combined treatment with AFB(1) and EB or EM succeeded to improve all the tested
      parameters towards the control values although it did not normalize them.
      Moreover, the improvement was pronounced in the group received EM plus AFB(1). It
      could be concluded that EB and EM have the ability to tightly bind AFB(1) in the
      gastrointestinal tract of fish resulting in decreasing its bioavailability.
      Moreover, the two tested clays were safe and can be used as potential aflatoxin
      binders in animal feed.

PMID- 20817255
TI  - Exposure assessment of dioxins and dioxin-like PCBs in pasteurised bovine milk
      using probabilistic modelling.
AB  - Quantitative exposure assessment is a useful technique to investigate the risk
      from contaminants in the food chain. The objective of this study was to develop a
      probabilistic exposure assessment model for dioxins (PCDD/Fs) and dioxin-like
      PCBs (DL-PCBs) in pasteurised bovine milk. Mean dioxins and DL-PCBs (non-ortho
      and mono-ortho PCBs) concentrations (pg WHO-TEQ g(-1)) in bovine milk were
      estimated as 0.06 +/- 0.07 pg WHO-TEQ g(-1) for dioxins and 0.08 +/- 0.07 pg WHO
      TEQ g(-1) for DL-PCBs using Monte Carlo simulation. The simulated model estimated
      mean exposure for dioxins was 0.19 +/- 0.29 pg WHO-TEQ kg(-1)bw d(-1) and 0.14 +/
      0.22 pg WHO-TEQ kg(-1) bw d(-1) and for DL-PCBs was 0.25 +/- 0.30 pg WHO-TEQ kg(
      1) bw d(-1) and 0.19 +/- 0.22 pg WHO-TEQ kg(-1) bw d(-1) for men and women,
      respectively. This study showed that the mean dioxins and DL-PCBs exposure from
      consumption of pasteurised bovine milk is below the provisional maximum tolerable
      monthly intake of 70 pg TEQ kg(-1) bw month(-1) (equivalent of 2.3 pg TEQ kg(-1)
      bw d(-1)) recommended by the Joint FAO/WHO Expert Committee on Food Additives and
      Contaminants (JECFA). Results from this study also showed that the estimated
      dioxins and DL-PCBs concentration in pasteurised bovine milk is comparable to
      those reported in previous studies.

PMID- 20817256
TI  - Insecticide survival and behavioral avoidance in the lacewings Chrysoperla
      externa and Ceraeochrysa cubana.
AB  - Insecticide impact on non-target species, such as insect predators and
      parasitoids, is an ever-growing concern in agriculture and recent studies have
      been shifting focus from lethal to sub-lethal effects since they may prevail in
      field conditions, although more difficult to assess. Synthetic insecticides are
      the main concern, but the recent spread of biopesticide use in agriculture draws
      attention, particularly the main botanical insecticide currently in use -
      azadirachtin. Here we assessed the lethal and behavioral sub-lethal response of
      predatory larvae of the lacewing species Chrysoperla externa and Ceraeochrysa
      cubana to two frequently used synthetic insecticides, malathion and permethrin,
      and to the bioinsecticide azadirachtin. The recommended field concentration of
      the synthetic insecticides led to low survival time of lacewing larvae from both
      species, in contrast with azadirachtin. However, all three compounds led to 100%
      mortality of the lacewing larvae from both species. Insecticide repellence (i.e.,
      avoidance without contact) was similar for both synthetic insecticides in both
      species, but azadirachtin was a stronger repellent for C. externa, but not C.
      cubana. In addition, insecticide irritability (i.e., avoidance after contact)
      occurred in both lacewing species to all three insecticides tested. The notion
      that natural compounds are safer than synthetic compounds to non-target species
      is refuted in the present study, which also detected significant irritability to
      all of the insecticides regardless of their origin, and species-specific
      repellence elicited particularly by azadirachtin. Therefore, bioinsecticides
      should not be exempted from risk assessment, and non-target sub-lethal effects
      should not be neglected when considering potential insecticide use in
      agriculture.

PMID- 20817257
TI  - Vulnerability of biomarkers in the indigenous mollusk Anodonta cygnea to
      spontaneous pollution in a transition country.
AB  - The aim of this study was to estimate the sensitivity of biomarkers of stress and
      exposure in the bivalve mollusk Anodonta cygnea to spontaneous anthropogenic
      activities typical for the Western Ukraine. Three sites were examined during
      spring, summer and autumn: an agricultural site (A); the cooling pond of nuclear
      power plant (N) and a forestry close to the municipal water inlet (F). Common
      temporal changes of a battery of biochemical markers in the gills and hemolymph
      and morphological characteristics were shown by discriminant functional analysis.
      Classification trees built on the basis of the screened biomarkers demonstrated
      persistent peculiarities at each site: genotoxicity (nuclear abnormalities) at
      site A and endocrine disruption (high levels of vitellogenin-like proteins (Vtg
      LP) in hemolymph) at site F. Interim local effects were best characterized by
      metallothionein (MT) concentrations, lipid peroxidation (LPO), activities of
      glutathione S-transferase and lactate dehydrogenase, and the conditional index of
      the gills. In autumn, the mollusks from the three sites revealed the highest
      differences in pollution status: the activation of antioxidant defense and
      cholinesterase were typical for site A, highest levels of MT related to high
      levels of Cu and Cd in the water at site B, and a steep increase in the level of
      Vtg-LP and the decrease of lysosomal membrane stability were recorded at the site
      selected as reference (F). The biomarker alterations recorded at site F were
      later related to an emergency event at the municipal dump located nearby. Thus,
      our case study demonstrated the reliability of using biomarkers of exposure to
      assess both long-term and accidental environmental pollution loads.

PMID- 20817258
TI  - Mineralization of isoproturon, mecoprop and acetochlor in a deep unsaturated
      limestone and sandy aquifer.
AB  - Isoproturon (N,N-dimethyl-N'-[4-(1-methylethyl)phenyl]urea), mecoprop (MCPP) (2
      (4-chloro-2-methylphenoxy)propanoic acid) and acetochlor (2-chloro-N-(2
      ethoxymethyl)-N-(2-ethyl-6-methylphenyl)acetamide) are agricultural pesticides
      that may leach through the vadose zone down to groundwater. Sediment samples were
      collected from intact sediment cores from 0 to 59 m below surface, including
      soil, unsaturated limestone and aquifer sand. In the unsaturated limestone, the
      initial pesticide concentrations (0.5-100 MUg kg(-1)) did not systematically
      affect the proportion of mineralized pesticides or the kinetics. However, in the
      aquifer, mecoprop and to some degree isoproturon mineralization was found to
      increase with increasing initial concentration (0.5-100 MUg L(-1) equivalent to 1
      220 MUg kg(-1)) demonstrating the importance of using environmentally relevant
      concentrations when predicting pesticide fate. The mineralization of isoproturon,
      mecoprop and acetochlor was studied in 40 samples at low concentrations (1-3 MUg
      L(-1)) and specific pesticide-mineralizing bacteria were enumerated using 14C
      MPN. Presence of the mineralizers documented a degradation potential of the
      pesticides within the catchment. The number of mineralizers varied from <0.18 to
      >16000 g(-1) and was not found to correlate with depth. Mecoprop, isoproturon and
      acetochlor were substantially mineralized in the soils (19-44% after 8months
      incubation at 1 MUg kg(-1)), in sub-surface unsaturated limestone samples (<=2%
      for acetochlor, <=21% for isoproturon and <=31% for mecoprop) and in aquifer
      samples (4-28% for mecoprop, <=4.7% for isoproturon and <=5.6% for acetochlor).
      The finding of isoproturon and acetochlor mineralization in deep aquifers is
      novel and important for the evaluation of the fate of these pesticides, as even
      low mineralization rates can be important in aquifers exhibiting long residence
      times.

PMID- 20817259
TI  - CYP 1A1 polymorphism and organochlorine pesticides levels in the etiology of
      prostate cancer.
AB  - Organochlorine pesticides (OCPs) and polymorphisms of xenobiotic metabolizing
      enzymes are reported to be associated with the possible risk of prostate cancer.
      OCPs are endocrine disruptors (EDs) which may act by disrupting the physiologic
      function of endogenous hormones and therefore possibly increase prostate cancer
      risk. CYP1A1 metabolizes several carcinogens and estrogens, etc. and hence
      polymorphism of this gene has been reported to be associated with prostate cancer
      risk. We studied 70 newly diagnosed prostate cancer patients and 61 age-matched
      healthy male controls. OCP levels in blood were determined by using gas
      chromatography-mass spectrometry (GC-MS) and CYP1A1 polymorphisms were analyzed
      by allele-specific PCR and RFLP-PCR methods. Significantly higher levels of beta
      HCH, gamma-HCH and p,p'-DDE were found in cases as compared to controls (p
      values=0.04, 0.008, and 0.01, respectively). Higher levels of gamma-HCH were
      observed in advanced stages of prostate cancer cases (<or=T(2) vs. >or=T(3)), (p
      value=0.04). Dieldrin was found significantly higher in cases with initial stages
      (p-value=0.03). We did not observe any correlation between prostate cancer and
      CYP1A1 polymorphisms. Hence, higher level of OCPs, especially beta-HCH, gamma-HCH
      and p,p'-DDE might be associated with prostate cancer risk.

PMID- 20817260
TI  - Sewage effluent clean-up reduces phosphorus but not phytoplankton in lowland
      chalk stream (River Kennet, UK) impacted by water mixing from adjacent canal.
AB  - Information is provided on phosphorus in the River Kennet and the adjacent Kennet
      and Avon Canal in southern England to assess their interactions and the changes
      following phosphorus reductions in sewage treatment work (STW) effluent inputs. A
      step reduction in soluble reactive phosphorus (SRP) concentration within the
      effluent (5 to 13 fold) was observed from several STWs discharging to the river
      in the mid-2000s. This translated to over halving of SRP concentrations within
      the lower Kennet. Lower Kennet SRP concentrations change from being highest under
      base-flow to highest under storm-flow conditions. This represented a major shift
      from direct effluent inputs to a within-catchment source dominated system
      characteristic of the upper part to the catchment. Average SRP concentrations in
      the lower Kennet reduced over time towards the target for good water quality.
      Critically, there was no corresponding reduction in chlorophyll-a concentration,
      the waters remaining eutrophic when set against standards for lakes. Following
      the up gradient input of the main water and SRP source (Wilton Water), SRP
      concentrations in the canal reduced down gradient to below detection limits at
      times near its junction with the Kennet downstream. However, chlorophyll
      concentrations in the canal were in an order of magnitude higher than in the
      river. This probably resulted from long water residence times and higher
      temperatures promoting progressive algal and suspended sediment generations that
      consumed SRP. The canal acted as a point source for sediment, algae and total
      phosphorus to the river especially during the summer months when boat traffic
      disturbed the canal's bottom sediments and the locks were being regularly opened.
      The short-term dynamics of this transfer was complex. For the canal and the
      supply source at Wilton Water, conditions remained hypertrophic when set against
      standards for lakes even when SRP concentrations were extremely low.

PMID- 20817261
TI  - Water body and riparian buffer strip characteristics in a vineyard area to
      support aquatic pesticide exposure assessment.
AB  - The implementation of a geodata-based probabilistic pesticide exposure assessment
      for surface waters in Germany offers the opportunity to base the exposure
      estimation on more differentiated assumptions including detailed landscape
      characteristics. Since these characteristics can only be estimated using field
      surveys, water body width and depth, hydrology, riparian buffer strip width,
      ground vegetation cover, existence of concentrated flow paths, and riparian
      vegetation were characterised at 104 water body segments in the vineyard region
      Palatinate (south-west Germany). Water body segments classified as permanent
      (n=43) had median values of water body width and depth of 0.9m and 0.06m,
      respectively, and the determined median width:depth ratio was 15. Thus, the
      deterministic water body model (width=1m; depth=0.3m) assumed in regulatory
      exposure assessment seems unsuitable for small water bodies in the study area.
      Only 25% of investigated buffer strips had a dense vegetation cover (>70%) and
      allow a laminar sheet flow as required to include them as an effective pesticide
      runoff reduction landscape characteristic. At 77 buffer strips, bordering field
      paths and erosion rills leading into the water body were present, concentrating
      pesticide runoff and consequently decreasing buffer strip efficiency. The
      vegetation type shrubbery (height>1.5m) was present at 57 (29%) investigated
      riparian buffer strips. According to their median optical vegetation density of
      75%, shrubberies may provide a spray drift reduction of 72+/-29%. Implementing
      detailed knowledge in an overall assessment revealed that exposure via drift
      might be 2.4 and via runoff up to 1.6 fold higher than assumed by the
      deterministic approach. Furthermore, considering vegetated buffer strips only by
      their width leads to an underestimation of exposure by a factor of as much as
      four. Our data highlight that the deterministic model assumptions neither
      represent worst-case nor median values and therefore cannot simply be adopted in
      a probabilistic approach.

PMID- 20817262
TI  - Monthly district level risk of dengue occurrences in Sakon Nakhon Province,
      Thailand.
AB  - The paper deals with the incidence of the Dengue Virus Infection (DVI) in the 18
      districts of Sakon Nakhon Province, Thailand, from January 2005 to December 2007.
      Using a statistical and autoregressive analysis to smooth incidence data, we have
      constructed yearly and monthly district level maps of the DVI distribution. It is
      found that the DVI incidence is very correlated with weather conditions and
      higher occurrences are observed in the three most populated districts Wanon
      Niwat, Sawang Daen Din and Mueang Sakon Nakhon, and the virus transmission period
      spans from mid-summer to mid-rainy seasons (from April to August). Employing a
      Generalized Linear Model (GLM), we found that the DVI incidences were related
      with current meteorological (monthly minimum temperature, past 2-month cumulated
      rainfall) and socio-economical (population of 0-4years old, per capita number of
      public small water wells, and proportion of villages with primary schools)
      covariates. And using the GLM under the climate change conditions (A1B scenario
      of IPCC), we found that the higher risk of DVI spreads from the three most
      populated districts to less populated ones, and the period of virus transmission
      increases from 5 to 9months to include part of winter, summer and rainy seasons
      (from March to November) during which 6%, 61% and 33% of districts will be at
      low, medium and high risk of DVI occurrences, respectively.

PMID- 20817263
TI  - Wastewater management through the ages: a history of mankind.
AB  - Although much has been written about the history of water supply systems, there
      is a lack of corresponding information on wastewater management. This is
      surprising since the lack of sanitation affects human development to the same or
      even greater extent as the lack of clean water. While there may be an added
      stigma to discussing waste treatment, sanitation is widely perceived as meriting
      a significant claim on financial and political resources as well on the evolution
      of mankind. A literature review is presented on the evolution of wastewater
      management through the ages and its concurrent impact on human health and
      environment. Hopefully this information will improve the awareness of the past
      with a view to impacting future policies and technical developments. The review
      highlights the connection of environmental contamination with the ability to
      measure it, as well as the ways pollution control has been changed by advances in
      scientific knowledge. Attention is also drawn to the effects of political and
      societal events on wastewater management. A sanitation timeline has been
      constructed pointing out significant developments in the treatment of wastewater
      and improvements in analytical environmental chemistry. This review has been
      written in the belief that historical research showing the collective experience
      and "philosophy of sanitation" can provide inspiration to face future challenges.

PMID- 20817264
TI  - Potential molecular mechanisms for combined toxicity of arsenic and alcohol.
AB  - Arsenic is a ubiquitous environmental factor that has been identified as a risk
      factor for a wide range of human diseases. Alcohol is clearly a toxic substance
      when consumed in excess. Alcohol abuse results in a variety of pathological
      effects, including damages to liver, heart, and brain, as well as other organs,
      and is associated with an increased risk of certain types of cancers. In history,
      arsenic-contaminated beers caused severe diseases. There are populations who are
      exposed to relatively high levels of arsenic in their drinking water and consume
      alcohol at the same time. In this focused review, we aim to discuss important
      molecular mechanisms responsible for arsenic toxicity and potential combined
      toxic effects of alcohol and arsenic.

PMID- 20817266
TI  - Social capital and the course of depression: six-month prospective cohort study.
AB  - BACKGROUND: Previous research has found an inverse cross-sectional relationship
      between an individual's access to social capital (defined as resources embedded
      within social networks) and depression, but this relationship has not been
      rigorously tested in prospective research. This is the first longitudinal study
      to evaluate the effect of social capital on the course of depression and
      subjective quality of life in a clinical population. METHODS: This was a six
      month prospective cohort study of people with depression in primary care
      achieving a follow-up rate of 91.3% (n=158). Depression was measured with the HAD
      D and social capital using the Resource Generator-UK. Potential confounding
      variables including socio-demographics, socio-economic status, depression
      history, social support, life events and attachment style were also measured.
      RESULTS: Social capital had no independent effect on the course of depression,
      though an interaction of access to social capital and attachment style was
      significantly related to change in quality of life alongside multiple covariates.
      LIMITATIONS: The study used a small sample; a short follow-up period; no measure
      of ecological social capital; no genetic components; and only two time points.
      CONCLUSIONS: Emotional support is important for the alleviation of depression.
      Additionally, people with depression may require a secure attachment style to
      derive the full benefit of their social capital.

PMID- 20817265
TI  - Risedronate metal complexes potentially active against Chagas disease.
AB  - In the search for new metal-based drugs for the treatment of Chagas disease, the
      most widespread Latin American parasitic disease, novel complexes of the
      bioactive ligand risedronate (Ris, (1-hydroxy-1-phosphono-2-pyridin-3-yl
      ethyl)phosphonate), [M(II)(Ris)(2)].4H(2)O, where M?Cu, Co, Mn and Ni, and
      [Ni(II)(Ris)(2)(H(2)O)(2)].H(2)O were synthesized and characterized by using
      analytical measurements, thermogravimetric analyses, cyclic voltammetry and
      infrared and Raman spectroscopies. Crystal structures of [Cu(II)(Ris)(2)].4H(2)O
      and [Ni(II)(Ris)(2)(H(2)O)(2)].H(2)O were solved by single crystal X-ray
      diffraction methods. The complexes, as well as the free ligand, were evaluated in
      vitro against epimastigotes and intracellular amastigotes of the parasite
      Trypanosoma cruzi, causative agent of Chagas disease. Results demonstrated that
      the coordination of risedronate to different metal ions improved the
      antiproliferative effect against T. cruzi, exhibiting growth inhibition values
      against the intracellular amastigotes ranging the low micromolar levels. In
      addition, this strong activity could be related to high inhibition of farnesyl
      diphosphate synthase enzyme. On the other hand, protein interaction studies
      showed that all the complexes strongly interact with albumin thus providing a
      suitable means of transporting them to tissues in vivo.

PMID- 20817267
TI  - Differential outcome of bipolar patients receiving antidepressant monotherapy
      versus combination with an antimanic drug.
AB  - INTRODUCTION: Despite antidepressants are widely used in treating bipolar
      depression, there is much debate about their utility and their potential dangers,
      involving mood switches and suicidality. Our hypothesis was that the pattern of
      initial antidepressant prescription, i.e., alone (AM) or in combination with
      stabilizers (AC) might impact the long-term outcome of patients with bipolar
      disorder (BP). We aimed to test this hypothesis and to identify outcome measures
      that could be predicted by initial AM or AC treatment in patients with BP.
      METHODS: We included 95 patients with DSM-IV BP from a pool of 138 patients
      following a BP program. Patients were rated for initial AM vs. AC treatment when
      they were first seen in primary care and subdivided into two groups accordingly.
      Differences in their clinical course were sought investigating course both
      retrospectively and prospectively (mean follow-up 10 years). Primary outcome
      measures comprised suicidality and switch rate. RESULTS: There were significantly
      more patients who switched in the AM group than in the AC group. The number of
      suicide attempts was higher in the AM group. Significance was retained after
      performing logistic regression. LIMITATIONS: Sample size was small and severe BP
      patients might be overrepresented in this sample. DISCUSSION: Initial AM
      treatment of patients subsequently diagnosed as BP may entrain a course
      characterized by higher proneness to switch and suicidal behaviour. Accurate
      initial diagnosis of bipolar depression should prompt combined treatment with
      antimanic drugs.

PMID- 20817268
TI  - Expression of Dpp6 in mouse embryonic craniofacial development.
AB  - Dipeptidyl-peptidase-like protein 6 (DPP6), a member of the dipeptidyl
      aminopeptidase family, plays distinct roles in brain development, but its
      expression in embryonic craniofacial development is unknown. The expression
      pattern of Dpp6 in the maxillofacial region during mouse embryonic craniofacial
      development was analyzed by whole-mount in situ hybridization on sections and by
      real-time PCR analysis. Dpp6 expression was detected during mouse embryonic
      craniofacial development in embryos 11-13.5 days post-coitum (dpc). Real-time PCR
      showed high Dpp6 expression present in 11.5-13.5dpc, and this then decreased as
      development of maxillofacial region progressed. The expression pattern of Dpp6
      suggests that Dpp6 may be involved in embryonic craniofacial development.

PMID- 20817269
TI  - Smoking rates among schizophrenia patients in Japan.
AB  - According to the meta-analysis performed by de Leon and Diaz, the smoking rate
      was higher among schizophrenia patients than in the general population with the
      exception of the populations of Japan and Colombia. The purpose of this study was
      to reexamine the association between schizophrenia and smoking among Japanese
      schizophrenia patients using objective measures. The sample comprised 172
      schizophrenia inpatients (mean age: 54years; 55% male). Participants were asked
      by a psychiatrist whether they currently smoked, and their answers were confirmed
      by the Fagerstrom Test for Nicotine Dependence and a measurement of the carbon
      monoxide level in expired air. Data on 7496 Japanese people obtained from the
      national survey of health were used as the control group. Seventy schizophrenia
      patients (40.7%) were identified as smokers; the smoking rate was higher among
      men in their 50s (66.7%) and among women in their 40s (54.6%). The smoking rate
      was 24.2% in the control group, and multiple logistic regression analysis showed
      that this percentage was significantly higher in the schizophrenia than in the
      control group (odds ratio: 2.17), adjusting for sex and age. The association
      between smoking rate and schizophrenia is consistent across countries, including
      Japan.

PMID- 20817270
TI  - Long-term prostate cancer survivors with low socioeconomic status reported worse
      mental health-related quality of life in a population-based study.
AB  - OBJECTIVE: To explore whether socioeconomic status (SES) was associated with
      health-related quality of life (HRQL) and health care use among long-term
      prostate cancer survivors. PATIENTS AND METHODS: Through urologists in the
      Comprehensive Cancer Center South, all 5- to 10-year prostate cancer survivors
      known in the Eindhoven Cancer Registry without disease progression were invited
      to complete the 36-item Short Form Health Survey (SF-36), the Expanded Prostate
      Cancer Index, and the Dutch sexual activities module. Multivariate linear
      regression assessed the effect of SES (based on home value and household income)
      on HRQL and health care use. RESULTS: Five-hundred eighty-four patients (response
      rate 81%) were included. Survivors with a low SES exhibited lower mental SF-36
      scores (6-16 points on a 0-100 scale), independent of sociodemographic and
      clinical characteristics (P < .05), and hardly any differences in physical SF-36
      subscales, sexual function, and urinary and bowel function and bother. Presence
      of serious comorbidity had a stronger predictive value for HRQL than SES. Health
      care use did not seem to be associated with SES. CONCLUSIONS: Prostate cancer
      survivors with a low SES exhibited a worse mental but not physical HRQL than
      those with a higher SES. Long-term health outcomes of patients with low SES may
      be maximized by paying extra attention to comorbid conditions.

PMID- 20817271
TI  - Bone-anchored sling for male stress urinary incontinence: assessment of
      complications.
AB  - OBJECTIVES: To evaluate the complications associated with the male bone-anchored
      sling (BAS) to determine the appropriate preoperative counseling for men
      considering surgery. The BAS is a surgical option for the treatment of stress
      urinary incontinence (SUI) due to intrinsic sphincter deficiency. METHODS: We
      retrospectively reviewed 119 men who had undergone 140 BAS procedures for SUI
      from May 2000 to May 2009 at our institution. All complications were recorded
      during the follow-up visits. Pad test and questionnaire results were recorded, as
      available. RESULTS: BAS was performed in 140 cases for 119 men with SUI. Mean
      patient age was 65.8 years (range 23-89). Main etiologies for SUI included
      previous treatment of prostate cancer (82.4%), neurologic dysfunction (12.6%),
      and previous transurethral resection of the prostate (3.6%). Recurrent SUI, de
      novo urge incontinence, and wound infection were the most frequent complications
      encountered (25.2%, 17.6%, and 16%, respectively). The 3 most common reasons for
      reoperation included bulking agent injection for recurrent SUI (5.9%), sling
      revision for bone screw dislodgement (5.9%), and sling revision for recurrent SUI
      (5.0%). Overall complication and reoperation rate for the index cases was 58.8%
      and 26.9%, respectively. CONCLUSIONS: The incidence of complications after male
      BAS placement might be greater than previously reported. Patient counseling
      before surgery regarding the potential complications is important. Men treated
      for prostate cancer should be informed of the risk of recurrent SUI. In
      appropriately selected patients, we believe the BAS is a reasonable surgical
      option; however, the risk of postoperative complication is not equivocal.

PMID- 20817272
TI  - The acute effects of increased intra-abdominal pressure on testicular tissue: an
      experimental study in pigs.
AB  - OBJECTIVES: To evaluate the acute effects of increased intra-abdominal pressure
      (IAP) on testicular germ cell apoptosis and the expressions of endothelial nitric
      oxide synthase (eNOS), inducible nitric-oxide synthase (iNOS), and Johnson's
      scores in testicular tissue. MATERIALS AND METHODS: Twelve male pigs weighing 52
      to 55 kg were divided into 2 groups as group 1 (n = 6; gasless [control]) and
      group 2 (n = 6; 20 mm Hg IAP with CO(2) pneumoperitoneum for 4 hours). In the
      second group, left laparoscopic nephrectomy was performed during the CO(2)
      insufflation period. The right testes of pigs were removed. Testicular germ cell
      apoptosis, expressions of eNOS and iNOS, and Johnson's scores were evaluated for
      each group. RESULTS: The control group (group 1) exhibited low apoptotic cell
      level and low iNOS and eNOS level in testes. IAP (group 2) resulted in marked
      increases in germ cell apoptosis, eNOS, and iNOS compared with the control group
      (group 1) (P <.05). However, no significant difference was noted in Johnson's
      scores between the 2 groups (P >.05). Moreover, Leydig cell hyperplasia,
      congestion, and necrosis, which were not documented in the control group, were
      seen in the study group. CONCLUSIONS: The purpose of the present study was to
      evaluate whether IAP could affect germ cell apoptosis and NOS concentrations in
      the testes after laparoscopic procedures in an animal model. In such an animal
      model simulating laparoscopic procedures, we demonstrated that high-pressure and
      long-lasting CO(2) insufflation cause testicular changes in the acute period.

PMID- 20817273
TI  - Comparison of 12-core versus 8-core prostate biopsy: multivariate analysis of
      large series of US veterans.
AB  - OBJECTIVES: To investigate the impact of additional biopsy cores on prostate
      cancer diagnosis among US veterans. The reported rate of positive biopsy results
      varies from 20% to 40%. METHODS: We analyzed 1546 consecutive initial prostate
      biopsy procedures (8-core and 12-core biopsy protocols) at the Atlanta VA Medical
      Center. Both biopsy protocols targeted the peripheral zone. Cancer detection
      rates were compared between the 2 protocols in univariate and multivariate
      analyses with results expressed as odds ratios and corresponding 95% confidence
      intervals. Characteristics of cancer detected were also compared. Sensitivity
      analyses were performed for different population subgroups. RESULTS: The overall
      positive biopsy rate was 49.9%, 51.2% in the 8-core group and 49.2% in the 12
      core group. There was no difference between the 2 biopsy groups (adjusted odds
      ratio = 0.97, 95% confidence interval = 0.76-1.25). Advanced age and high body
      mass index were significantly associated with higher likelihood of prostate
      cancer, whereas larger prostate volumes were associated with lower risk.
      CONCLUSIONS: In this large series of prostate biopsy procedures, in which the
      peripheral zone was well targeted, there was no evidence that 12-core biopsy
      improved the likelihood of prostate cancer diagnosis compared with 8-core biopsy.
      As such, the results of this cohort from a US veteran population suggest that
      targeting the peripheral zone is more important than the absolute number of
      biopsy cores. However, in certain subgroups of patients with specific clinical
      characteristics, such as those with very large prostates, more cores may be
      required. Further studies are needed to identify such characteristics.

PMID- 20817274
TI  - Reassessment of renal cell carcinoma lymph node staging: analysis of patterns of
      progression.
AB  - OBJECTIVES: To evaluate the prognostic value of lymph node (LN) metastasis and
      the therapeutic role of LN dissection (LND) in patients with renal cell
      carcinoma. METHODS: We reviewed the medical records of 1503 patients who had
      undergone nephrectomy from 1990 to 2007. The patients were stratified according
      to the number, location, and size of LN metastases. The disease-free survival,
      cancer-specific survival, and survival relative to the preoperative suspicion of
      LN metastasis were analyzed. RESULTS: Of the 1503 patients, 726 (48.3%) had Stage
      pN0, 37 (2.5%) had Stage pN+, including 16 with pN1 and 21 with pN2, and 740
      (49.2%) had Stage pNx. The average number of LNs removed was 5 (range 1-33), and
      the average size of the metastasized LNs was 2.4 cm (range 0.8-6). Of the
      patients without preoperative clinical evidence of LN metastasis, 203 underwent
      LND; all had Stage pN0. The LN stage was a significant predictor of distant
      metastasis-free survival (P = .002) and cancer-specific survival (P = .001)
      between the pNx/pN0 and pN+ groups but not between the pN1 and pN2 groups.
      Metastasized LN size (<3 vs >=3 cm) also significantly predicted for distant
      metastasis-free survival (P = .003) and cancer-specific survival (P = .001). In
      LN-positive patients, LND improved local recurrence-free survival but not distant
      metastasis-free survival or cancer-specific survival. CONCLUSIONS: The current LN
      staging system, which is dependent on the number of metastatic LNs, did not
      significantly correlate with the prognosis in patients with renal cell carcinoma.
      In contrast, LN size (<3 vs >=3 cm) better reflected the effect of this disease
      on survival. The therapeutic role of LND might be limited.

PMID- 20817275
TI  - Generation and validation of canine single chain variable fragment phage display
      libraries.
AB  - Single chain variable region fragments (scFvs) are composed of an immunoglobulin
      (Ig) variable heavy (VH) and variable light (VL) chain joined by a flexible
      serine-glycine linker. They represent the smallest antibody fragments that
      maintain antigen specificity and they hold significant potential for therapeutic
      antigen targeting in vivo. Here we report on the design and validation of a
      series of degenerate primers that amplify the recombined variable regions of
      canine Ig heavy and light chain genes from lymphocyte cDNA. We show that these VH
      and VL amplicons can be randomly combined by a flexible linker using splicing by
      overlap extension PCR to form scFv constructs that can be expressed on the
      surface of M13 bacteriophage. To demonstrate that scFvs with specificity for
      previously encountered antigens are contained within these scFv phage display
      libraries we used simple panning procedures to isolate canine parvovirus (CPV)
      specific scFvs from a library made from the splenocytes of a dog immunized
      against CPV. These studies reveal the feasibility of this approach for generating
      diverse canine scFv libraries and pave the way toward future studies to isolate
      canine antigen-specific scFv of interest that may be tested as targeting agents
      for the treatment of infectious, inflammatory and neoplastic diseases in the dog.

PMID- 20817276
TI  - The interleukin 10 response in ovine Johne's disease.
AB  - Johne's disease is an enteric mycobacterial infection of ruminants that has
      significant global economic impact. The classic host reaction is one of an early
      T-cell mediate immune response, with predominant interferon gamma (IFNgamma)
      activity; there is subsequent lowering of this response as animals reach the
      terminal stages of disease. Interleukin (IL)-10, which can suppress Th1-type and
      enhance Th2-type cytokine production, is considered to play a role in the later
      stages of Johne's disease. To determine the role of IL-10 throughout the course
      of Johne's disease we studied groups of sheep with either no Johne's disease
      (n=10), natural infection (n=30) or experimental infection (n=58). Disease status
      of the animals was comprehensively assessed by culture of Mycobacterium avium
      subsp. paratuberculosis (Mptb), histopathology and serology. Antigen-specific IL
      10 secretion in peripheral blood of sheep exposed to Mptb was significantly
      higher than in control animals (P<0.001) as early as 4 months post-inoculation,
      and increased progressively. In ileal and jejunal lymph node cells, IL-10
      secretion was also significantly higher in animals that were exposed to Mptb
      compared to controls (P<0.05). The early IL-10 response seen in peripheral blood
      cells may be a reflection of early responses at sites of Mptb infection. IL-10
      secretion from ileal and jejunal lymph node cells was significantly higher in
      exposed animals with no lesions or with paucibacillary lesions when compared to
      animals with multibacillary lesions. These novel findings demonstrate that
      increased IL-10 activity commences soon after exposure to the causative
      mycobacterium and may play a role in determining disease outcome.

PMID- 20817277
TI  - Reversal of laryngotracheal separation in paediatric patients.
AB  - OBJECTIVE: Laryngotracheal separation (LTS) is an effective and reliable
      definitive treatment for intractable aspiration. A major advantage of this
      treatment for intractable aspiration is its' potential reversibility. Should the
      underlying disorder improve, a reversal of the procedure may be attempted. This
      has been successfully achieved in the adult population. To our knowledge, no
      previous cases have been reported of successful reversal of LTS in children.
      METHODS: A retrospective review from 2003 to 2010 identified four cases of
      intractable aspiration treated with LTS in our department. Two of these patients
      displayed objective evidence of sufficient recovery of their underlying
      aspiration to consider reversal. Patient selection for reversal was dependent
      upon successful oral intake for 9 months along with videofluoroscopic evidence of
      normal or minimally impaired swallow. RESULTS: Two children who were successfully
      treated for intractable aspiration with LTS demonstrated objective evidence of
      recovery sufficient to attempt reversal. Both children underwent successful
      surgical reversal of LTS using a cricotracheal resection with end-to-end
      anastamosis, similar to that used in treatment of subglottic stenosis. Both
      children can now tolerate oral diet and their speech and language development is
      in line with their overall developmental level. CONCLUSIONS: Laryngotracheal
      separation is an effective and reliable definitive treatment for intractable
      aspiration facilitating protection of the airway and allowing safe swallowing
      with unimpeded respiration, but with the major drawback of loss of phonation. To
      our knowledge, we document the first two cases of successful LTS reversal in
      children.

PMID- 20817279
TI  - Task effects in the mid-fusiform gyrus: a comparison of orthographic,
      phonological, and semantic processing of Chinese characters.
AB  - The left mid-fusiform gyrus is repeatedly reported to be involved in visual word
      processing. Nevertheless, it is controversial whether this area responds to
      orthographic processing of reading. To examine this idea, neural activity was
      measured using functional magnetic resonance imaging in the present study while
      subjects performed phonological, semantic, and orthographic tasks with Chinese
      characters under equivalent task difficulties. One region in the left mid
      fusiform gyrus exhibited greater activity during the orthographic task than
      during the phonological and semantic tasks, which did not differ, suggesting that
      this region is involved in orthographic processing to a greater extent than
      phonological or semantic processing. In addition, a region in the right mid
      fusiform gyrus exhibited a similar effect. This right mid-fusiform activity may
      relate to the use of pictorial Chinese characters.

PMID- 20817278
TI  - Iron-export ferroxidase activity of beta-amyloid precursor protein is inhibited
      by zinc in Alzheimer's disease.
AB  - Alzheimer's Disease (AD) is complicated by pro-oxidant intraneuronal Fe(2+)
      elevation as well as extracellular Zn(2+) accumulation within amyloid plaque. We
      found that the AD beta-amyloid protein precursor (APP) possesses ferroxidase
      activity mediated by a conserved H-ferritin-like active site, which is inhibited
      specifically by Zn(2+). Like ceruloplasmin, APP catalytically oxidizes Fe(2+),
      loads Fe(3+) into transferrin, and has a major interaction with ferroportin in
      HEK293T cells (that lack ceruloplasmin) and in human cortical tissue. Ablation of
      APP in HEK293T cells and primary neurons induces marked iron retention, whereas
      increasing APP695 promotes iron export. Unlike normal mice, APP(-/-) mice are
      vulnerable to dietary iron exposure, which causes Fe(2+) accumulation and
      oxidative stress in cortical neurons. Paralleling iron accumulation, APP
      ferroxidase activity in AD postmortem neocortex is inhibited by endogenous
      Zn(2+), which we demonstrate can originate from Zn(2+)-laden amyloid aggregates
      and correlates with Abeta burden. Abnormal exchange of cortical zinc may link
      amyloid pathology with neuronal iron accumulation in AD.

PMID- 20817280
TI  - Acute coronary syndromes: finding meaning in OASIS 7.

PMID- 20817282
TI  - Conditioning of the heart: from pharmacological interventions to local and remote
      protection: possible implications for clinical practice.
AB  - Ischemic preconditioning is a natural protective mechanism by which brief
      episodes of ischemia protect the heart or other organs from the deleterious
      effects of ischemia-reperfusion injury. Ischemic preconditioning was demonstrated
      in animals more than 20 years ago, and subsequent studies in humans showed a
      dramatic protective effect on the heart. This method did not translate into
      clinical practice partially due to difficulty in application of conditioning. At
      the same time, multiple drugs were assessed, but none proved to be beneficial in
      large scale studies for myocardial protection. Although multicenter studies are
      still lacking, it was recently demonstrated in reasonable sized studies that in
      patients undergoing percutaneous coronary interventions or suffering from
      myocardial infarction, remote ischemic conditioning has beneficial protective
      effect. With more studies we may see translation into clinical practice in the
      near future.

PMID- 20817283
TI  - Aborted myocardial infarction in intracoronary compared with standard intravenous
      abciximab administration in patients undergoing primary percutaneous coronary
      intervention for ST-elevation myocardial infarction.
AB  - BACKGROUND: Abciximab reduces major adverse cardiac events (MACEs) in patients
      with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous
      coronary intervention (PCI). Intracoronary (IC) abciximab bolus application might
      be more effective than a standard intravenous (IV) bolus. So far the occurrence
      of aborted MI, a new therapeutic target of effective treatment in STEMI, has not
      been evaluated in IC versus IV abciximab administration in STEMI patients
      undergoing primary PCI. METHODS: To investigate the extent of aborted MI, 154
      patients undergoing primary PCI were randomized to either IC (n=77) or IV (n=77)
      bolus abciximab administration with subsequent 12-hour intravenous infusion. For
      assessment of infarct size and extent of microvascular obstruction, all patients
      underwent late enhancement magnetic resonance imaging (MRI). Aborted MI was
      defined by major (>= 50%) ST-segment resolution and a lack of subsequent cardiac
      enzyme rise >= 2 the upper normal limit. We also assessed the occurrence of true
      aborted MI defined as the absence of myocardial necrosis in MRI. RESULTS: The
      incidence of aborted MI was significantly higher in the IC group (p=0.04); true
      aborted MI was only observed in the IC abciximab group (p=0.01). At multivariable
      logistic regression analysis, IC abciximab application was a significant
      independent predictor of true aborted MI (p=0.03). Aborted MI patients had an
      excellent prognosis at 6-month follow-up with no MACE as compared to 24 events in
      patients with non-aborted MI. CONCLUSIONS: IC bolus application of abciximab in
      STEMI patients undergoing primary PCI results in a higher incidence of aborted MI
      and subsequent improved clinical outcome.

PMID- 20817284
TI  - Evidence-based review: quality of life following head and neck intensity
      modulated radiotherapy.
AB  - Inverse planned Intensity modulated radiotherapy (IMRT) can minimize the dose to
      normal structures and therefore can reduce long-term radiotherapy-related
      morbidity and may improve patients' long-term quality of life. Despite
      overwhelming evidence that IMRT can reduce late functional deficits in patients
      with head and neck cancer, treated with radiotherapy, a review of the published
      literature produced conflicting results with regard to quality of life outcomes.
      Following a critical appraisal of the literature, reasons for the discrepant
      outcomes are proposed.

PMID- 20817281
TI  - Double-dose versus standard-dose clopidogrel and high-dose versus low-dose
      aspirin in individuals undergoing percutaneous coronary intervention for acute
      coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial.
AB  - BACKGROUND: Clopidogrel and aspirin are the most commonly used antiplatelet
      therapies for percutaneous coronary intervention (PCI). We assessed the effect of
      various clopidogrel and aspirin regimens in prevention of major cardiovascular
      events and stent thrombosis in patients undergoing PCI. METHODS: The CURRENT
      OASIS 7 trial was undertaken in 597 centres in 39 countries. 25,086 individuals
      with acute coronary syndromes and intended early PCI were randomly assigned to
      double-dose (600 mg on day 1, 150 mg on days 2-7, then 75 mg daily) versus
      standard-dose (300 mg on day 1 then 75 mg daily) clopidogrel, and high-dose (300
      325 mg daily) versus low-dose (75-100 mg daily) aspirin. Randomisation was done
      with a 24 h computerised central automated voice response system. The clopidogrel
      dose comparison was double-blind and the aspirin dose comparison was open label
      with blinded assessment of outcomes. This prespecified analysis is of the 17,263
      individuals who underwent PCI. The primary outcome was cardiovascular death,
      myocardial infarction, or stroke at 30 days. Analyses were by intention to treat,
      adjusted for propensity to undergo PCI. This trial is registered with
      ClinicalTrials.gov, number NCT00335452. FINDINGS: 8560 patients were assigned to
      double-dose and 8703 to standard-dose clopidogrel (8558 and 8702 completed 30-day
      follow-up, respectively), and 8624 to high-dose and 8639 to low-dose aspirin
      (8622 and 8638 completed 30-day follow-up, respectively). Compared with the
      standard dose, double-dose clopidogrel reduced the rate of the primary outcome
      (330 events [3.9%] vs 392 events [4.5%]; adjusted hazard ratio 0.86, 95% CI 0.74
      0.99, p=0.039) and definite stent thrombosis (58 [0.7%] vs 111 [1.3%]; 0.54 [0.39
      0.74], p=0.0001). High-dose and low-dose aspirin did not differ for the primary
      outcome (356 [4.1%] vs 366 [4.2%]; 0.98, 0.84-1.13, p=0.76). Major bleeding was
      more common with double-dose than with standard-dose clopidogrel (139 [1.6%] vs
      99 [1.1%]; 1.41, 1.09-1.83, p=0.009) and did not differ between high-dose and low
      dose aspirin (128 [1.5%] vs 110 [1.3%]; 1.18, 0.92-1.53, p=0.20). INTERPRETATION:
      In patients undergoing PCI for acute coronary syndromes, a 7-day double-dose
      clopidogrel regimen was associated with a reduction in cardiovascular events and
      stent thrombosis compared with the standard dose. Efficacy and safety did not
      differ between high-dose and low-dose aspirin. A double-dose clopidogrel regimen
      can be considered for all patients with acute coronary syndromes treated with an
      early invasive strategy and intended early PCI. FUNDING: Sanofi-Aventis and
      Bristol-Myers Squibb.

PMID- 20817285
TI  - Searching for genetic determinants of normal tissue radiosensitivity--are we on
      the right track?

PMID- 20817286
TI  - Adaptive radiotherapy for bladder cancer reduces integral dose despite daily
      volumetric imaging.
AB  - We studied the integral radiation dose in 27 patients who had adaptive
      radiotherapy for bladder cancer using kilo voltage cone beam CT imaging. Compared
      to conventional radiotherapy the reduction in margin and choice of best plan of
      three for the day resulted in a lower total dose in most patients despite daily
      volumetric imaging.

PMID- 20817287
TI  - Efficacy and tolerance of salvage radiotherapy after radical prostatectomy, with
      emphasis on high-risk patients suited for adjuvant radiotherapy.
AB  - BACKGROUND AND PURPOSE: Goals of this study are to report the outcomes and
      tolerance of salvage radiotherapy (SRT) after prostatectomy, to identify risk
      factors for failure after SRT and to evaluate how these results compare with
      published results of immediate post-operative adjuvant radiotherapy (ART).
      MATERIAL AND METHODS: Men receiving SRT for elevated PSA levels after radical
      prostatectomy (RP) were included. Biochemical progression-free survival (bPFS),
      overall survival (OS) and disease-specific survival (DSS) were estimated. Risk
      factors for biochemical failure and death were evaluated. Late toxicity and
      quality of life were evaluated. Secondary bPFS (defined as bPFS from
      prostatectomy until progression after radiotherapy) was calculated for high-risk
      patients (pT3 and/or positive surgical margins) in order to compare SRT outcomes
      with ART. RESULTS: 197 Men were included. Five-year bPFS after SRT was 59% (95%
      CI 49-69%). Five-year OS and DSS were 90% (85-96%) and 97% (93-100%),
      respectively. Capsular perforation (pT>=T3), negative surgical margins and serum
      PSA>1 ng/ml at the start of RT were significant predictors of lower bPFS.
      Patients without any negative factors had a 5-year bPFS of 89%. No severe late
      toxicity was reported. Five-year secondary bPFS for SRT in high-risk patients was
      78% and comparable with published results for ART. CONCLUSIONS: Salvage
      radiotherapy for patients with organ-confined prostate cancer was effective and
      well tolerated. SRT outcomes were comparable with published ART results for high
      risk patients. Initially monitoring serum PSA and considering early SRT for these
      patients are not harmful and might be a valuable alternative for immediate ART.

PMID- 20817288
TI  - Validation of the Total Dysphagia Risk Score (TDRS) as a predictive measure for
      acute swallowing dysfunction induced by chemoradiotherapy for head and neck
      cancers.
AB  - BACKGROUND AND PURPOSE: Methods for predicting acute swallowing dysfunction in
      patients with head and neck cancers undergoing definitive chemoradiotherapy have
      not been established. We investigated the validity of the Total Dysphagia Risk
      Score (TDRS) as a predictive measure for this morbidity. MATERIALS AND METHODS:
      Forty-seven patients with head and neck cancers who underwent definitive
      chemoradiotherapy between December 1998 and March 2006 were reviewed
      retrospectively. Median age was 63 years (range, 16-81). Almost all patients
      underwent platinum-based concomitant chemoradiotherapy. Factors of the TDRS were
      as follows: T-classification, neck irradiation, weight loss, primary tumour site
      and treatment modality. Patients were classified into three risk groups according
      to the TDRS. RESULTS: Swallowing dysfunction was observed in 27 patients (57%) as
      RTOG grade 2 or higher acute morbidity. This classification was significantly
      associated with grade 2 or higher acute swallowing dysfunction (P<0.001). In ROC
      (receiver operator characteristic) analysis, the cut-off value of TDRS was set at
      18 (sensitivity=0.81; specificity=0.85). Prediction of severe (grade >= 3) acute
      swallowing dysfunction was similarly obtained. CONCLUSION: The TDRS is a useful
      tool to predict acute swallowing dysfunction induced by chemoradiotherapy for
      head and neck cancers.

PMID- 20817289
TI  - The relationship between external beam radiotherapy dose and chronic urinary
      dysfunction--a methodological critique.
AB  - PURPOSE: To perform a methodological critique of the literature evaluating the
      relationship between external beam radiotherapy dose/volume parameters and
      chronic urinary dysfunction to determine why consistent associations between dose
      and dysfunction have not been found. METHODS AND MATERIALS: The radiotherapy
      literature was reviewed using various electronic medical search engines with
      appropriate keywords and MeSH headings. Inclusion criteria comprised of; English
      language articles, published between 1999 and June 2009, incorporating
      megavoltage external beam photons in standard-sized daily fraction. A
      methodological critique was then performed, evaluating the factors affected in
      the quantification of radiotherapy dose and chronic urinary dysfunction. RESULTS:
      Nine of 22 eligible studies successfully identified a clinically and
      statistically significant relationship between dose and dysfunction. Accurate
      estimations of external beam radiotherapy dose were compromised by the frequent
      use of dosimetric variables which are poor surrogates for the dose received by
      the lower urinary tract tissue and do not incorporate the effect of daily
      variations in isocentre and bladder position. The precise categorization of
      chronic urinary dysfunction was obscured by reliance on subjective and aggregated
      toxicity metrics which vary over time. CONCLUSIONS: A high-level evidence-base
      for the relationship between external beam radiotherapy dose and chronic urinary
      dysfunction does not currently exist. The quantification of the actual external
      beam dose delivered to the functionally important tissues using dose accumulation
      strategies and the use of objective measures of individual manifestations of
      urinary dysfunction will assist in the identification of robust relationships
      between dose and urinary dysfunction for application in widespread clinical
      practice.

PMID- 20817290
TI  - Multivariate analysis of quality of life outcome for nasopharyngeal carcinoma
      patients after treatment.
AB  - PURPOSE: The study analyzed the prognostic factors of quality of life (QoL) for
      patients with nasopharyngeal carcinoma (NPC) after treatment, with focusing on
      the therapeutic benefits of the technological advances in radiotherapy (RT).
      MATERIALS AND METHODS: A cross-sectional investigation was conducted to assess
      the QoL of 356 NPC patients with cancer-free survival of more than 2 years. Among
      them, 106 patients were treated by two-dimensional RT (2DRT), 108 by 2DRT plus
      three-dimensional conformal RT (3DCRT) boost, 58 by 3DCRT alone, and 84 by
      intensity-modulated RT (IMRT). The QoL was assessed by the EORTC QLQ-C30
      questionnaire and QLQ-H&N35 module. The clinical difference of QoL scores between
      groups was calculated using Cohen's D coefficient. RESULTS: We found NPC
      survivors who had a higher education level or annual family income and who had
      received more advanced RT treatments had better QoL outcomes. Compared with 2DRT,
      the impact of 3DCRT was small on most scales and moderate (Cohen's D: 0.53-0.67)
      on emotional functioning, pain, and mouth opening; the impact of IMRT was
      moderate on nine scales and large (Cohen's D: 0.80-0.88) on swallowing, social
      eating, teeth, and mouth opening. CONCLUSIONS: In addition to socioeconomic
      levels, advances in RT technique played a significant role in improving QoL of
      NPC patients.

PMID- 20817291
TI  - Clinical significance of multi-leaf collimator positional errors for volumetric
      modulated arc therapy.
AB  - BACKGROUND AND PURPOSE: Multi-leaf collimator (MLC) positional errors occur
      during intensity modulated radiation therapy (IMRT) and volumetric modulated arc
      therapy (VMAT) deliveries. The impact of such errors has been evaluated for IMRT
      but not VMAT. The purpose of this work is to understand how random and systematic
      VMAT MLC positional errors affect the patient dose distribution. MATERIALS AND
      METHODS: Eight head and neck single arc (360 degrees ) VMAT treatment plans were
      created. Random and two types of systematic MLC errors were simulated for error
      magnitudes of 0.25, 0.5, 1, 2 and 5mm. The two types of systematic MLC errors
      were: (1) MLC banks are shifted in the same direction (left or right) and (2) MLC
      banks are shifted in opposing directions resulting in smaller or larger field
      shapes. The MLC errors were simulated, for all control points, on both banks of
      active MLC leaves only. RESULTS: There is a linear correlation of MLC errors with
      gEUD for all error types. The gEUD dose sensitivities with MLC error for the
      PTV70 were -0.2, -0.9, -2.8 and 1.9 Gy/mm for random, systematic shift,
      systematic close and systematic open MLC errors, respectively. The sensitivity of
      VMAT plans to MLC positional errors was similar to those of IMRT plans with less
      than 50 segments but much less than those created for a step and shoot with more
      than 50 segments or sliding-window delivery technique. To maintain the PTV70 to
      within 2% would require that MLC open/close errors be within 0.6mm. CONCLUSIONS:
      Radiation therapy centers should have adequate quality assurance programs in
      place to assess open/close MLC errors (i.e. leaf gap errors) as they tend to be
      more impactful than random or systematic MLC shift errors.

PMID- 20817292
TI  - Long-term human pluripotent stem cell self-renewal on synthetic polymer surfaces.
AB  - Realization of the full potential of human pluripotent stem cells (hPSCs) in
      regenerative medicine requires the development of well-defined culture conditions
      for their long-term growth and directed differentiation. Current practices for
      maintaining hPSCs generally utilize empirically determined combinations of feeder
      cells and other animal-based products, which are expensive, difficult to isolate,
      subject to batch-to-batch variations, and unsuitable for cell-based therapies.
      Using a high-throughput screening approach, we identified several polymers that
      can support self-renewal of hPSCs. While most of these polymers provide support
      for only a short period of time, we identified a synthetic polymer poly(methyl
      vinyl ether-alt-maleic anhydride) (PMVE-alt-MA) that supported the long-term
      attachment, proliferation and self-renewal of HUES1, HUES9, and iPSCs. The hPSCs
      cultured on PMVE-alt-MA maintained their characteristic morphology, expressed
      high levels of markers of pluripotency, and retained a normal karyotype. Such
      cost-effective, polymer-based matrices that support long-term self-renewal and
      proliferation of hPSCs will not only help to accelerate the translational
      perspectives of hPSCs, but also provide a platform to elucidate the underlying
      molecular mechanisms that regulate stem cell proliferation and differentiation.

PMID- 20817293
TI  - Osteoinductive silk-silica composite biomaterials for bone regeneration.
AB  - Osteoinductive and biodegradable composite biomaterials for bone regeneration
      were prepared by combining silk fibroin with silica particles. The influence of
      these composite systems on osteogenesis was evaluated with human mesenchymal stem
      cells (hMSCs) subjected to osteogenic differentiation. hMSCs adhered,
      proliferated, and differentiated towards osteogenic lineages on silk/silica
      films. The addition of the silica to the silk films influenced gene expression
      leading to upregulation of bone sialoprotein (BSP) and collagen type 1 (Col 1)
      osteogenic markers. Evidence for early bone formation in the form of collagen
      fibers and apatite nodules was obtained on the silk/silica films. Collagen fibers
      were closely associated with apatite deposits and overall collagen content was
      higher for the silica containing samples. Also, smaller sized silica particles
      (24 nm-2 MUm) with large surface area facilitated silica biodegradation in vitro
      through particle dissolution, leading to ~5-fold decrease in silica content over
      10 weeks. These results indicate the suitability of silk/silica composite system
      towards bone regeneration, where degradation/remodeling rates of the organic and
      inorganic components can be controlled.

PMID- 20817294
TI  - An intelligent sarco-endoplasmic reticulum Ca2+ store: release and leak channels
      have differential access to a concealed Ca2+ pool.
AB  - Simultaneous recording of cytosolic and sarco-endoplasmic reticulum (SR/ER)
      luminal free calcium concentrations ([Ca(2+)](i) and [Ca(2+)](L), respectively)
      supports the notion that release channels (RyRs and IP(3)Rs) use a concealed
      Ca(2+) source, likely to be associated with intra-SR/ER Ca(2+) binding proteins,
      whereas SR/ER Ca(2+) leak channels can only access free luminal Ca(2+). We
      hypothesize that Ca(2+) is trapped by oligomers of luminal Ca(2+)-binding
      proteins and that the opening of release channels induces the rapid liberation of
      this "concealed" Ca(2+) source associated with intra-ER Ca(2+) buffers. Our
      hypothesis may also clarify why SERCA pumps potentiate Ca(2+) release and explain
      quantal characteristics and refractory states of Ca(2+) release process.

PMID- 20817295
TI  - Effect of haptic supplementation on postural stabilization: A comparison of fixed
      and mobile support conditions.
AB  - It is well known in the literature of haptic supplementation that a "light touch"
      (LT) with the index finger on a stable surface increases postural stability. In
      view of potential application in the domain of mobility aids, it should however
      be demonstrated that haptic supplementation is effective even when provided by an
      unstable stick support. The present study aimed to explore the stabilizing effect
      of a three-digit "light grip" (LG) of different supports (fixed or mobile stick)
      in young people. Eleven participants (M=25.9 years) were tested in an upright
      standing task in six experimental conditions in which the mobility of the given
      support and its resistance in opposite direction to the body movement were
      manipulated. The RMS variability and the range of postural oscillations were
      measured. The results confirmed that the stabilizing effect of haptic
      supplementation is independent from the nature of the support (fixed or mobile)
      when sufficiently large sway-related contact forces on the fingers are provided.
      Future applications of this "mobile stick paradigm" to complex situations while
      targeting different groups of participants may help to approach everyday life
      situations in which an informational stick could potentially be of assistance to
      gain stability and mobility.

PMID- 20817296
TI  - Microarray-based genotyping of Salmonella: inter-laboratory evaluation of
      reproducibility and standardization potential.
AB  - Bacterial food-borne infections in humans caused by Salmonella spp. are
      considered a crucial food safety issue. Therefore, it is important for the risk
      assessments of Salmonella to consider the genomic variation among different
      isolates in order to control pathogen-induced infections. Microarray technology
      is a promising diagnostic tool that provides genomic information on many genes
      simultaneously. However, standardization of DNA microarray analysis is needed
      before it can be used as a routine method for characterizing Salmonella isolates
      across borders and laboratories. A comparative study was designed in which the
      agreement of data from a DNA microarray assay used for typing Salmonella spp.
      between two different labs was assessed. The study was expected to reveal the
      possibility of obtaining the same results in different labs using different
      equipment in order to evaluate the reproducibility of the microarray technique as
      a first step towards standardization. The low-density array contains 281 57-60
      mer oligonucleotide probes for detecting a wide range of specific genomic marker
      genes associated with antibiotic resistance, cell envelope structures, mobile
      genetic elements and pathogenicity. Several critical methodology parameters that
      differed between the two labs were identified. These related to printing
      facilities, choice of hybridization buffer, wash buffers used following the
      hybridization and choice of procedure for purifying genomic DNA. Critical
      parameters were randomized in a four-factorial experiment and statistical
      measures of inter-lab consistency and agreement were performed based on the kappa
      coefficient. A high level of agreement (kappa=0.7-1.0) in microarray results was
      obtained even when employing different printing and hybridization facilities,
      different procedures for purifying genomic DNA and different wash buffers.
      However, less agreement (Kappa=0.2-0.6) between microarray results were observed
      when using different hybridization buffers, indicating this parameter as being
      highly critical when transferring a standard microarray assay between
      laboratories. In conclusion, this study indicates that DNA microarray assays can
      be reproduced in at least two different facilities, which is a pre-requisite for
      the development of standard guidelines.

PMID- 20817297
TI  - Ecotoxicological impact assessment of heavy metals in core sediments of a
      tropical estuary.
AB  - Down core variation of heavy metals in three sediment cores from Cochin estuary
      was studied. The average concentration of iron, manganese, nickel, copper, zinc,
      cadmium, lead and mercury in each slices of sediment was determined. Quality of
      the sediments were evaluated based on sediment quality guidelines, pollution load
      index, and sum of toxic units and with effect range low/effect range median and
      threshold effect level/probable effect level values of environmental protection
      agency guidelines. The degree of contamination for each station was determined.
      The results of the study revealed higher concentration of heavy metals in surface
      layers than in deeper ones. The concentration of heavy metals in some stations
      exceeded the effect range median levels, which represents a probable effect range
      with in which adverse biological effects frequently occur. The spatial variation
      of heavy metals showed more contamination in the downstream at Pathalam
      industrial site. Statistical analysis showed that the correlation among different
      parameters differs with respect to stations. The present study highlighted severe
      heavy metal contamination of Cochin estuary with increased rate of deposition.

PMID- 20817298
TI  - Cadmium-induced lignification restricts soybean root growth.
AB  - The effects of cadmium (Cd), a well-known environmental pollutant with high
      toxicity to plants, were tested on root growth, cell viability, phenylalanine
      ammonia-lyase (PAL) soluble plus cell wall-bound peroxidase (POD) activities,
      hydrogen peroxide (H(2)O(2)) levels, and the content and monomeric composition of
      lignin in soybean (Glycine max) roots. Three-day-old seedlings were cultivated in
      half-strength Hoagland's solution (pH 6.0), with or without 25-100 MUM CdCl(2) in
      a growth chamber (25 degrees C, 12/12-h light/dark photoperiod, irradiance of 280
      MUmolm(-2)s(-1)) for 24h. In general, root length and the fresh and dry weights
      decreased followed by loss of cell viability after Cd treatment. PAL activity,
      soluble and cell wall-bound POD activities, and H(2)O(2) and lignin contents
      increased significantly after Cd exposure. The lignin monomeric composition of Cd
      exposed roots revealed a significant increase of p-hydroxyphenyl (H) and syringyl
      (S) units. These results suggest that the effects caused by Cd may be due to
      excessive production of monolignols forming lignin, which solidifies the cell
      wall and restricts root growth.

PMID- 20817299
TI  - Use of sewage sludge as secondary fuel in a cement plant: human health risks.
AB  - Since 2008, sewage sludge is being used as alternative fuel in a cement plant
      placed in Vallcarca (Catalonia, Spain). To evaluate the temporal trend of the
      environmental levels of polychlorinated dibenzo-p-dioxins and dibenzofurans
      (PCDD/Fs) and a number of metals (As, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Sn, Tl, V,
      and Zn), as well as the potentially associated human health risks, samples of
      soil, herbage, and air were collected around the facility, after approximately
      one year of the permanent partial substitution of fuel. The temporal evolution of
      the pollutant levels was assessed by comparing the measured concentrations (2009)
      with those from samples collected in previous surveys (2003 and 2006) at the same
      sampling sites. The concentrations of PCDD/Fs in herbage and soil were 0.10 and
      1.11 ng I-TEQ.kg-1 dw, respectively, values very similar to those found in our
      previous surveys. For metals, although a clear tendency could not be observed,
      there were fluctuations through time. In this study, the levels of metals, which
      had not been analyzed in previous campaigns, were also determined in air,
      additionally to soil and vegetation. Airborne metal concentrations were similar
      to those found in other industrial areas worldwide. The human health risks for
      the population living around the cement plant were comparable to those obtained
      in previous studies, when petroleum coke was exclusively used as combustible,
      being in both cases tolerable according to the international standards.

PMID- 20817300
TI  - Lupus-derived monoclonal autoantibodies against apoptotic chromatin recognize
      acetylated conformational epitopes.
AB  - OBJECTIVE: Nuclear components targeted by autoantibodies are a characteristic
      feature of the autoimmune disease systemic lupus erythematosus (SLE). The
      nucleosome, a major autoantigen, is released in patients with SLE as a result of
      a disturbed apoptosis and/or an insufficient clearance of apoptotic debris.
      During apoptosis the nucleosome is modified, thereby creating more immunogenic
      epitopes. Subsequently, epitope spreading will lead to the formation of
      autoantibodies against unmodified chromatin components. However, characterization
      of B cell epitopes specific for apoptotic chromatin modifications is hampered by
      the fact that the existing monoclonal antibodies (mAbs) were originally selected
      on non-apoptotic chromatin. Here, we describe a novel approach for generating
      mAbs from lupus mice that are specific for apoptosis-induced chromatin
      modifications. METHODS: Hybridomas were generated from pre-diseased and diseased
      lupus mice using standard fusion methods. Selection occurred on isolated
      apoptotic chromatin. Antibodies were further characterized by ELISA, western blot
      and immunofluorescence staining with apoptotic and non-apoptotic chromatin/cells.
      In addition, reactivity was determined with subnucleosomal complexes and with
      nucleosomes treated with trypsin or DNase I. Finally, reactivity was determined
      with cells treated with the histone deacetylase inhibitor TSA. RESULTS: Most
      generated mAbs appeared to be nucleosome specific with a clear preference for
      apoptotic nucleosomes compared to normal nucleosomes. Although the exact
      elucidation of the epitopes of these mAbs specific for apoptosis-associated
      nucleosome modifications remains a major challenge, the epitopes contain both DNA
      and histones, whereby the histone tails play a role in establishing the epitopes.
      Most importantly, the conformational epitopes of these nucleosome-specific
      antibodies seem to contain acetylated residues. CONCLUSIONS: Our approach,
      yielding a new panel of anti-apoptotic-chromatin antibodies, should facilitate
      the discovery of more apoptosis-induced chromatin modifications and their
      identification as key autoantigens in the pathogenesis of SLE.

PMID- 20817301
TI  - Diagnostic performance of Baveno IV criteria in cirrhotic patients with upper
      gastrointestinal bleeding: analysis of the F7 liver-1288 study population.
AB  - BACKGROUND & AIMS: The definition of failure to control bleeding agreed upon at
      the Baveno IV consensus meeting, included the Adjusted Blood Requirement Index
      [ABRI: number of blood units/(final-initial hematocrit+0.01)]. ABRI >=0.75
      denotes failure. However, timing for hematocrit measurements was not defined. The
      aims of this study were: (1) to assess the Baveno IV criteria performance to
      classify treatment success or failure to control bleeding at 5 days, (2) to
      determine the appropriate timing for hematocrit. METHODS: Two hundred and forty
      two cirrhotic patients with gastrointestinal bleeding were independently
      classified by three clinical experts according to the Baveno IV criteria, by
      analysis of the database of a randomized trial. ABRI was calculated by using the
      closest hematocrit to the 5 day time point from the first trial product
      administration (ABRI-1) or after the latest transfusion within the 5-day period
      (ABRI-2). The gold standard for success/failure for 5-day control of bleeding was
      the clinical judgment of the three independent observers based on all the
      clinical and follow-up data. RESULTS: Inter-observer agreement for the final
      outcome assessment was 0.82 and a final consensus was obtained in 236/242
      patients. Inter-observer agreement on patient classification with Baveno IV
      criteria was 0.70 with ABRI-1 and 0.84 with ABRI-2. c-statistics for correct
      patients classification were 0.86 for ABRI-1, 0.84 for ABRI-2, and 0.88 for
      Baveno IV criteria without ABRI. ABRI-1 caused misclassification of 27 patients
      and ABRI-2 of 39. CONCLUSIONS: Baveno IV criteria are accurate to assess outcome
      of patients with variceal bleeding. There is a substantial observer variability
      linked to timing of hematocrits for ABRI calculation. With the current definition
      ABRI does not add to the performance of the other criteria.

PMID- 20817302
TI  - Nonalcoholic fatty liver disease: the hepatic trigger of the metabolic syndrome.

PMID- 20817303
TI  - Spectral and thermodynamic properties of methanobactin from gamma-proteobacterial
      methane oxidizing bacteria: a case for copper competition on a molecular level.
AB  - Methanobactin (mb) is a low molecular mass copper-binding molecule analogous to
      iron-binding siderophores. The molecule is produced by many methanotrophic or
      methane oxidizing bacteria (MOB), but has only been characterized to date in one
      MOB, Methylosinus trichosporium OB3b. To explore the potential molecular
      diversity in this novel class of metal binding compound, the spectral (UV
      visible, fluorescent, and electron paramagnetic resonance) and thermodynamic
      properties of mb from two gamma-proteobacterial MOB, Methylococcus capsulatus
      Bath and Methylomicrobium album BG8, were determined and compared to the mb from
      the alpha-proteobacterial MOB, M. trichosporium OB3b. The mb from both gamma
      proteobacterial MOB differed from the mb from M. trichosporium OB3b in molecular
      mass and spectral properties. Compared to mb from M. trichosporium OB3b, the
      extracellular concentrations were low, as were copper-binding constants of mb
      from both gamma-proteobacterial MOB. In addition, the mb from M. trichosporium
      OB3b removed Cu(I) from the mb of both gamma-proteobacterial MOB. Taken together
      the results suggest mb may be a factor in regulating methanotrophic community
      structure in copper-limited environments.

PMID- 20817304
TI  - Successful treatment of two lung cancer patients with erlotinib following
      gefitinib-induced hepatotoxicity.
AB  - INTRODUCTION: Hepatotoxicity secondary to gefitinib, an oral tyrosine kinase
      inhibitor (TKI) against the epidermal growth factor receptor (EGFR), is under
      appreciated, even though it has a reported incidence of 10-20% in phase II
      trials. METHODS/RESULTS: We present two patients with non-small cell lung cancer
      (NSCLC) who developed grade 2/3 hepatotoxicity starting between 4 and 6 weeks
      after initiation of gefitinib, with toxicity peaking between 10 and 20 weeks.
      Both patients were switched to treatment with erlotinib, another EGFR TKI,
      without further development of hepatotoxicity. One patient with measurable
      metastatic disease achieved a durable near complete response while on erlotinib.
      The other patient experienced recurrence of hepatotoxicity when gefitinib was
      briefly reintroduced. CONCLUSIONS: Patients with NSCLC receiving gefitinib should
      undergo routine monitoring of liver enzymes. For those who develop gefitinib
      induced hepatotoxicity but are otherwise deriving clinical benefit, consideration
      can be given to switching to erlotinib.

PMID- 20817305
TI  - Chromosomal speciation revisited: rearranging theory with pieces of evidence.
AB  - The suggestion that chromosomal rearrangements play a role in speciation resulted
      from the observation that heterokaryotypes are often infertile. However, the
      first chromosomal speciation models were unsatisfactory and data available to
      test them was scarce. Recently, large amounts of data have become available and
      new theoretical models have been developed explaining how rearrangements
      facilitate speciation in the face of gene flow. Here, we re-examine theoretical
      predictions and revisit different sources of data. Although rearrangements are
      often associated with increased levels of divergence, unequivocal demonstration
      that their role in suppressing recombination results in speciation is often
      lacking. Finally, we question some previous predictions and suggest new empirical
      and theoretical approaches to understanding the relevance of rearrangements in
      the origin of species.

PMID- 20817306
TI  - Cerebral microbleeds and symptom severity of post-stroke depression: a magnetic
      resonance imaging study.
AB  - BACKGROUND: Cerebral microbleeds (CMBs) are common in stroke survivors, although
      their clinical significance in the development of psychiatric conditions
      following stroke remains unknown. This study examines the association between
      post-stroke depression (PSD) symptom severity and CMBs. METHODS: Amongst the 4088
      patients with acute ischemic stroke who had been admitted to the acute stroke
      unit of a university-affiliated regional hospital in Hong Kong, between December
      2004 and May 2009, 994 patients were recruited. A psychiatrist administered the
      Structural Clinical Interview for DSM-IV to all 994 patients and made a diagnosis
      of PSD three months after the index stroke. PSD symptom severity was assessed
      with the 15-item Geriatric Depression Scale (GDS). Seventy-eight patients were
      found to have PSD. The presence and location of CMBs were evaluated with magnetic
      resonance imaging (MRI). RESULTS: Seventy-eight patients (7.8%) had PSD. CMBs
      were identified in 20 PSD patients. Relative to the no-CMB group, the mean GDS
      score of patients with lobar CMBs was significantly higher (12.6+/-2.6 versus
      10.4+/-2.5, p=0.01 after adjusting for age, sex, global cognitive functions,
      neurological deficits and white matter hyperintensities). LIMITATIONS: Patients
      with more severe stroke, those who died before the three-month follow-up and
      those who became depressed later were excluded, as were those unable to give
      their consent due to dementia or aphasia. These selection biases may limit the
      generalizability of the findings. CONCLUSIONS: The results suggest that lobar
      CMBs may contribute to PSD symptom severity. The importance of CMBs in the
      pathogenesis of other psychiatric disorders in stroke survivors and other patient
      populations warrants further investigation.

PMID- 20817307
TI  - The effect of age on frontal lobe related cognitive functions of unmedicated
      depressed patients.
AB  - BACKGROUND: Aging is associated with a decline in frontal lobe related cognitive
      functioning of healthy subjects (i.e., executive functioning and higher-order
      cognition). Unipolar depression is associated with dysfunctions in similar
      cognitive domains--deficits that impact the functioning and quality of life of
      these patients. The effect of age on frontal lobe related cognitive functions of
      depressed patients, however, has not been adequately studied. The current study
      therefore assessed a wide age range of depressed patients and compared their
      frontal lobe related cognitive functions to that of matched healthy controls.
      Recruitment of unmedicated patients minimized the confounding effect of
      psychiatric medications. METHOD: Depressed patients and healthy controls were
      divided into three age groups (<25, 25-45, and 46-65 years of age) and matched in
      gender, age and education level (N total=170). Cognition was assessed using the
      Cambridge Neuropsychological Test Automated Battery (CANTAB). RESULTS: The
      depressed patients had deficits in cognitive planning/organization, working
      memory, and sustained attention compared to the healthy controls. Aging was
      associated with a decrease in frontal lobe related functioning. Except for
      working memory, no significant interactions were found between the age groups and
      the study group (depressed/healthy). CONCLUSIONS: Depressed patients are impaired
      in most domains of frontal lobe related cognitive functions. These deficits are
      already evident at an early age and persist in older age cohorts (despite an
      overall age related decline). These findings may help clarify the profile and
      course of cognitive deficits among depressed patients while providing tentative
      support for a developmental model of cognitive impairment in depression.

PMID- 20817308
TI  - B-1 cells temper endotoxemic inflammatory responses.
AB  - Sepsis syndrome is caused by inappropriate immune activation due to bacteria and
      bacterial components released during infection. This syndrome is the leading
      cause of death in intensive care units. Specialized B-lymphocytes located in the
      peritoneal and pleural cavities are known as B-1 cells. These cells produce IgM
      and IL-10, both of which are potent regulators of cell-mediated immunity. It has
      been suggested that B-1 cells modulate the systemic inflammatory response in
      sepsis. In this study, we conducted in vitro and in vivo experiments in order to
      investigate a putative role of B-1 cells in a murine model of LPS-induced sepsis.
      Macrophages and B-1 cells were studied in monocultures and in co-cultures. The B
      1 cells produced the anti-inflammatory cytokine IL-10 in response to LPS. In the
      B-1 cell-macrophage co-cultures, production of proinflammatory mediators (TNF
      alpha, IL-6 and nitrite) was lower than in the macrophage monocultures, whereas
      that of IL-10 was higher in the co-cultures. Co-culture of B-1 IL-10(-/-) cells
      and macrophages did not reduce the production of the proinflammatory mediators
      (TNF-alpha, IL-6 and nitrite). After LPS injection, the mortality rate was higher
      among Balb/Xid mice, which are B-1 cell deficient, than among wild-type mice
      (65.0% vs. 0.0%). The Balb/Xid mice also presented a proinflammatory profile of
      TNF-alpha, IL-6 and nitrite, as well as lower levels of IL-10. In the early phase
      of LPS stimulation, B-1 cells modulate the macrophage inflammatory response, and
      the main molecular pathway of that modulation is based on IL-10-mediated
      intracellular signaling.

PMID- 20817309
TI  - Addition of EEG improves accuracy of a logistic model that uses
      neuropsychological and cardiovascular factors to identify dementia and MCI.
AB  - To investigate whether addition of EEG would improve accuracy of a logistic model
      that uses neuropsychological assessment and cardiovascular history to identify
      dementia and mild cognitive impairment (MCI) as a single group, we collected data
      and constructed logistic models from a sample of 78 normal adults and 33 patients
      (aged 50-85 years). To determine accuracy, we compared logistic regression
      results to a geriatrician's diagnosis of MCI or dementia that included
      Alzheimer's disease, vascular dementia or mixed dementia. We found that the
      addition of EEG (non-linear complexity) to a logistic model that included both
      neuropsychological assessment (ADAS-Cog) and cardiovascular history increased
      overall accuracy from 80% to 92%. The logistic model identified dementia and MCI
      as a single group comprised of the following subgroups (with accuracies):
      Alzheimer's disease (92%; 12/13), vascular dementia (73%; 8/11), mixed dementia
      (100%; 4/4), and mild cognitive impairment (80%; 4/5). Whereas the analysis is
      limited by small sample sizes and mixing of diverse pathologies, the findings do
      provide support that the subgroups may share changes in neuropsychological,
      cardiovascular, and electroencephalographic factors (specifically ADAS-Cog total
      score, cardiovascular history, and EEG complexity). Taken together, the study
      results provide support that EEG might complement the clinician's evaluation of
      dementia and MCI.

PMID- 20817310
TI  - Distinct neuropsychological profiles of three major symptom dimensions in
      obsessive-compulsive disorder.
AB  - Recent neuroimaging studies have suggested that different symptom dimensions are
      mediated by partially distinct neural systems in obsessive-compulsive disorder
      (OCD). However, the correlations between neuropsychological profiles and symptom
      dimensions in OCD are unknown. The aim of this study was to examine the extent to
      which OCD symptom dimensions were associated with episodic memory and attention
      and executive functions. The symptom dimensions of 63 patients with OCD were
      assessed using both the Padua Inventory and the Y-BOCS symptom checklist. Then,
      we administered the Logical Memory (LM) subset of the Wechsler Memory Scale
      Revised (WMR-R) test and evaluated inhibition (Stroop test, Trail Making test)
      and cognitive flexibility (Digit Symbol test, Letter Fluency, and Category
      Fluency). While associations were observed between scores on the
      contamination/cleaning dimension and better performances on the LM and Trail
      Making tests, associations were also observed between scores on the
      aggressive/checking dimension and poorer performances on the Trail Making test.
      In addition, we found that scores on the symmetry/ordering dimension were
      associated with poorer performances on the LM and Trail Making tests. Our results
      support the hypothesis that different symptoms may represent distinct and
      partially overlapping neurocognitive networks in OCD patients.

PMID- 20817311
TI  - Serial and semantic encoding of lists of words in schizophrenia patients with
      visual hallucinations.
AB  - Previous research has suggested that visual hallucinations in schizophrenia are
      associated with abnormal salience of visual mental images. Since visual imagery
      is used as a mnemonic strategy to learn lists of words, increased visual imagery
      might impede the other commonly used strategies of serial and semantic encoding.
      We had previously published data on the serial and semantic strategies
      implemented by patients when learning lists of concrete words with different
      levels of semantic organisation (Brebion et al., 2004). In this paper we present
      a re-analysis of these data, aiming at investigating the associations between
      learning strategies and visual hallucinations. Results show that the patients
      with visual hallucinations presented less serial clustering in the non
      organisable list than the other patients. In the semantically organisable list
      with typical instances, they presented both less serial and less semantic
      clustering than the other patients. Thus, patients with visual hallucinations
      demonstrate reduced use of serial and semantic encoding in the lists made up of
      fairly familiar concrete words, which enable the formation of mental images.
      Although these results are preliminary, we propose that this different processing
      of the lists stems from the abnormal salience of the mental images such patients
      experience from the word stimuli.

PMID- 20817312
TI  - Exploring the genomes: from Arabidopsis to crops.
AB  - Model systems have played a crucial role for understanding biological processes
      at genetic, molecular and systems levels. Arabidopsis thaliana is one of the best
      studied model species for higher plants. Large genomic resources and mutant
      collections made Arabidopsis an excellent source for functional and comparative
      genomics. Rice and Brachypodium have a great potential to become model systems
      for grasses. Given the agronomic importance of grass crops, it is an attractive
      strategy to apply knowledge from Arabidopsis to grasses. Despite many efforts
      successful reports are sparse. Knowledge transfer should generally work best
      between orthologous genes that share functionality and a common ancestor. In
      higher plants, however, recent genome projects revealed an active and rapid
      evolution of genome structure, which challenges the concept of one-to-one
      orthologous mates between two species. In this study, we estimated on the example
      of protein families that are involved in redox related processes, the impact of
      gene expansions on the success rate for a knowledge transfer from Arabidopsis to
      the grass species rice, sorghum and Brachypodium. The sparse synteny between
      dicot and monocot plants due to frequent rearrangements, translocations and gene
      losses strongly impairs and reduces the number of orthologs detectable by
      positional conservation. To address the limitations of sparse synteny and
      expanded gene families, we applied for the detection of orthologs in this study
      orthoMCL, a sequence-based approach that allows to group closely related paralogs
      into one orthologous gene cluster. For a total of 49 out of 170 Arabidopsis genes
      we could identify conserved copy numbers between the dicot model and the grass
      annotations whereas approximately one third (34.7%, 59 genes) of the selected
      Arabidopsis genes lack an assignment to any of the grass genome annotations. The
      remaining 62 Arabidopsis genes represent groups that are considerably biased in
      their copy numbers between Arabidopsis and all or most of the three grass
      genomes.

PMID- 20817313
TI  - Plant aging and excess light enhance flavan-3-ol content in Cistus clusii.
AB  - Physiological studies on aging in perennials are mainly focused either on the
      primary metabolism or the hormonal regulation of the process. However, to our
      knowledge, the involvement of the secondary metabolism in this process has not
      yet been explored. Cistus clusii, a Mediterranean sclerophyllous evergreen bush,
      shows considerable amounts of flavan-3-ols in leaves. In the present study, we
      aimed at determining the impact of environmental conditions and plant aging in
      the flavan-3-ol content in C. clusii plants grown in field conditions, which
      included summer drought and recovery periods. Six-year-old plants suffered more
      from photo-oxidative stress, especially during excess light periods, and showed
      lower maximum photosynthetic rates than 1-year-old plants. C. clusii leaves
      accumulated (-)-epigallocatechin gallate in early summer, in a strong positive
      correlation with both the photon flux density and the photoperiod, but not with
      the plant water status. Moreover, C. clusii plants accumulated proanthocyanidins
      (polymeric flavan-3-ols) in leaves during summer. Older plants showed higher
      levels of proanthocyanidins and (-)-epicatechin, but only during late spring and
      summer. From the result of the present study, we conclude that excess light
      enhances flavan-3-ol content in C. clusii, a process enhanced as plants age due
      to increased excess light stress.

PMID- 20817314
TI  - Molecular cloning of IKKbeta from the mandarin fish Siniperca chuatsi and its up
      regulation in cells by ISKNV infection.
AB  - The IkappaB kinase beta (IKKbeta) plays crucial roles in regulating activation of
      nuclear factor-kappa B (NF-kappaB) in response to proinflammatory factors and
      microbial and viral infections. Here, we report the cloning of an IKKbeta cDNA
      (named SicIKKbeta) from the mandarin fish Siniperca chuatsi. The full-length cDNA
      is 4052bp and contains an ORF that encodes a predicted protein of 743-amino acid
      residues. The deduced amino acid sequence of SicIKKbeta has the same domain
      organization as human IKKbeta, which consists of a serine/threonine kinase
      domain, a leucine zipper motif and a putative helix-loop-helix motif.
      Quantitative RT-PCR showed that SicIKKbeta was ubiquitously expressed in tissues
      of mandarin fish, and its expression in mandarin fish fry (MFF-1) cells was up
      regulated during the course of ISKNV infection.

PMID- 20817315
TI  - Field validation of a dusting cloth for mycological surveillance of surfaces.
AB  - Efficient monitoring of surfaces for spores of filamentous fungi is essential for
      detecting minor contamination even when air samples test negative for fungi. This
      study evaluates and compares a pad prepared using a dusting cloth with Rodac
      contact plates and humidified swabs for detecting mycological contamination, and
      concludes that the new method is superior and cheaper.

PMID- 20817316
TI  - Risk of bacterial cross infection associated with inspiration through flow-based
      spirometers.
AB  - BACKGROUND: Bacterial contamination of spirometers has been documented in water
      sealed devices, mouthpieces, and connection tubes. Little information is
      available about bacterial contamination of flow-based apparatuses such as turbine
      type spirometers and pneumotachographs. Inspiration through contaminated
      equipment is a potential source of cross infection. To investigate bacteria
      mobilization (ie, bacteria detachment and aerosolization from the instrument)
      during routine spirometric testing, 2 types of flow-based spirometers were used.
      Bacteria mobilization during artificial inspiration through in-line filters or
      cardboard mouthpieces was evaluated. METHODS: Nine hundred workers undergoing
      periodic spirometric testing were enrolled at the occupational physician office
      in 30 sessions of 30 subjects each. The participants were asked to perform a
      forced vital capacity test in a turbine-type spirometer and in an unheated
      pneumotachograph fitted with disposable in-line filters or cardboard mouthpieces.
      To evaluate bacterial mobilization, an artificial inspiration was performed and
      bacterial growth determined. The bacterial growth analysis was assessed after the
      first and the thirtieth spirometric tests of each session without disinfecting
      the instruments between tests. In addition, instrument bacterial contamination
      was evaluated. RESULTS: No significant bacterial mobilization and instrument
      contamination were found in spirometric tests executed with in-line filters.
      Conversely, a significant bacterial mobilization and instrument contamination
      were observed in tests performed with cardboard mouthpieces. Differences between
      the 2 spirometers were not significant. CONCLUSION: In-line filters may
      effectively reduce the risk of bacterial cross infection. Inspiration through
      flow-based spirometers fitted with disposable cardboard mouthpieces is completely
      safe when combined with spirometer disinfection/sterilization between subjects.

PMID- 20817317
TI  - Outbreak of community-acquired methicillin-resistant Staphylococcus aureus skin
      infections among health care workers in a cancer center.
AB  - BACKGROUND: The incidence of community-acquired methicillin-resistant
      Staphylococcus aureus (CA-MRSA) soft tissue infections is rising. However, CA
      MRSA outbreaks among health care workers (HCWs) are rarely reported. We describe
      3 clusters of CA-MRSA soft tissue infections among HCWs and the subsequent
      transmission to a patient. METHODS: The first cluster of boils occurred in 4
      employees who worked in the ambulatory treatment clinic (area A) and 1 patient
      (PA1) who frequently visited area A. Three employees (EA1, EA2, and EA3) and PA1
      had positive cultures. Twelve employees in 2 geographically separate diagnostic
      imaging areas (areas B and C) reported recent or current boils of whom EB1, EB2,
      EB3, and EC1 had positive cultures. Molecular subtyping using pulse-field gel
      electrophoresis (PFGE) was performed on all 8 isolates and confirmed by the
      Centers for Disease Control and Prevention laboratory. RESULTS: Relatedness of
      the MRSA strain was confirmed by PFGE in 7 of 8 isolates. Only EB3 was not
      related to the prototype CA-MRSA strain. All 7 related MRSA strains contained the
      typical genetic organization of staphylococcal cassette chromosome (SCC)-mec type
      IVa plus genes encoding Panton-Valentine Leukocidin. EB3's strain contained SCC
      mec type II and was Panton-Valentine Leukocidin negative. A total of 171
      questionnaires was sent. Nine of the 85 HCWs who responded reported a recent or
      current history of boils. Infection control conducted an education program for
      employees in areas A, B, and C. CONCLUSION: Early identification and control of
      CA-MRSA infections among HCWs is important to limit horizontal transmission to
      patients. Future efforts should include educational programs and guidelines for
      reporting and treating HCWs with MRSA infections.

PMID- 20817318
TI  - Povidone-iodine against sodium hypochlorite as skin antiseptics in volunteers.
AB  - BACKGROUND: This study was conducted to compare the antiseptic efficacy of sodium
      hypochlorite of electrochemical production with that of povidone-iodine in human
      voluntaries. METHODS: Three areas of 25 cm(2) each were selected from the
      forearms; 1 was designated as control to determine the baseline bacterial count;
      and 2 more were selected to swab 10% povidone-iodine or 10% sodium hypochlorite.
      Every volunteer was studied on 3 separated occasions. Quantitative skin cultures
      were performed on agar plates containing a neutralizer. RESULTS: Forty-eight
      healthy subjects were enrolled for a total of 144 determinations for every
      antiseptic and control. The bacterial counts from the control areas showed a
      median of 1500 colony-forming units (CFU)/cm(2). For the areas treated with
      sodium hypochlorite, the median was 192 CFU/cm(2). For the areas treated with
      povidone-iodine, the median was 231 CFU/cm(2). When the colony counts for the
      areas treated with antiseptics were compared with those of the controls, the
      difference was significant (Kruskal-Wallis test (H) = 55.7, P < .001). The
      difference in counts between the areas treated with antiseptics was not
      significant (difference in z values <1960). CONCLUSION: The present study did not
      find differences in antiseptic action between 10% povidone iodine and 10% sodium
      hypochlorite.

PMID- 20817319
TI  - [Occupational health and cardiovascular prevention: Follow-up by telephone
      interview].

PMID- 20817320
TI  - Understanding social motor coordination.
AB  - Recently there has been much interest in social coordination of motor movements,
      or as it is referred to by some researchers, joint action. This paper reviews the
      cognitive perspective's common coding/mirror neuron theory of joint action,
      describes some of its limitations and then presents the behavioral dynamics
      perspective as an alternative way of understanding social motor coordination. In
      particular, behavioral dynamics' ability to explain the temporal coordination of
      interacting individuals is detailed. Two experiments are then described that
      demonstrate how dynamical processes of synchronization are apparent in the
      coordination underlying everyday joint actions such as martial art exercises,
      hand-clapping games, and conversations. The import of this evidence is that
      emergent dynamic patterns such as synchronization are the behavioral order that
      any neural substrate supporting joint action (e.g., mirror systems) would have to
      sustain.

PMID- 20817321
TI  - Mechanics of the Fouette turn.
AB  - The Fouette turn in classical ballet is performed repeatedly on one leg with
      swinging of the free limbs, producing a continued sequence of turns with one turn
      leading into the next. The purpose of this study was to determine the possible
      time history profiles of the twisting torque between the supporting leg and the
      remainder of the body that will allow continued performances of the Fouette turn.
      Simulations were performed using a model which comprised the supporting leg and
      the remainder of the body to find torque profiles that maintain the initial
      angular velocity so that the state after one revolution is the same as the
      initial state. The solution space of torque profiles was determined for various
      rotation times and coefficients of friction between foot and floor. As the time
      for one revolution became shorter the solution space became smaller and for a
      given turn time there was a lower limit on the coefficient of friction. As the
      frictional coefficient became smaller the solution space became smaller and for a
      given coefficient there was a lower limit on the turn time. Turns of a given
      tempo can be performed on floors with different friction by modifying the
      twisting torque profile. When a turn is completed with a net change in angular
      velocity this can be compensated for in the next turn by adjusting the twisting
      torque profile.

PMID- 20817322
TI  - Anticipation of tennis-shot direction from whole-body movement: the role of
      movement amplitude and dynamics.
AB  - While recent studies indicate that observers are able to use dynamic information
      to anticipate whole-body actions like tennis shots, it is less clear whether the
      action's amplitude may also allow for anticipation. We therefore examined the
      role of movement dynamics and amplitude for the anticipation of tennis-shot
      direction. In a previous study, movement dynamics and amplitude were separated
      from the kinematics of tennis players' forehand groundstrokes. In the present
      study, these were manipulated and tennis shots were simulated. Three conditions
      were created in which shot-direction differences were either preserved or
      removed: Dynamics-Present-Amplitude-Present (D(P)A(P)), Dynamics-Present
      Amplitude-Absent (D(P)A(A)), and Dynamics-Absent-Amplitude-Present (D(A)A(P)).
      Nineteen low-skill and 15 intermediate-skill tennis players watched the simulated
      shots and predicted shot direction from movements prior to ball-racket contact
      only. Percent of correctly predicted shots per condition was measured. On
      average, both groups' performance was superior when the dynamics were present
      (the D(P)A(P) and D(P)A(A) conditions) compared to when it was absent (the
      D(A)A(P) condition). However, the intermediate-skill players performed above
      chance independent of amplitude differences in shots (i.e., both the D(P)A(P) and
      D(P)A(A) conditions), whereas the low-skill group only performed above chance
      when amplitude differences were absent (the D(P)A(A) condition). These results
      suggest that the movement's dynamics but not their amplitude provides information
      from which tennis-shot direction can be anticipated. Furthermore, the successful
      extraction of dynamical information may be hampered by amplitude differences in a
      skill-dependent manner.

PMID- 20817323
TI  - The effect of treadmill walking on the stride interval dynamics of children.
AB  - Treadmills are commonly implemented in rehabilitation and laboratory settings to
      facilitate gait analysis and training. However, while this locomotor modality is
      often used with children, its effect on pediatric stride interval dynamics is
      unknown. This study investigated the stride interval persistence of 30
      asymptomatic children after completion of three to six 10-min walking trials
      comprised of: (i) overground walking (OW), (ii) unsupported treadmill walking
      (UTW), and (iii) handrail-supported treadmill walking (STW). The primary outcome
      measure was alpha, a quantifier of stride interval persistence obtained from
      detrended fluctuation analysis. Preferred walking speed, number of strides taken,
      stride interval duration, and stride interval coefficient of variation were also
      assessed. Stride interval persistence was significantly diminished during both
      treadmill walking conditions, compared to overground walking, with the largest
      decrease in alpha during UTW. Preferred speed, number of strides, and stride
      interval duration also differed between overground and treadmill walking, and
      older children demonstrated reduced stride interval variability compared to
      younger children. The observed treadmill and age effects on stride parameters may
      be due to a combination of differing locomotor constraints between overground and
      treadmill walking and developmental differences in sensory processing, cerebellar
      plasticity, and corticospinal involvement in locomotion.

PMID- 20817324
TI  - Use of phosphonyl carbanions in the synthesis of anti-inflammatory active
      phosphorus-containing fused heterocycles and relevance phosphonates.
AB  - The reaction of Horner-Emmons reactant carbanions with 2-acetyl-5-methyl furan 1
      and 2-acetyl-5-bromothiophene 9 resulted in phosphorus-containing fused bicyclic
      5,5-membered and 5,6-membered systems 5a-c and 12a-c, respectively, as major
      reaction products along with minor (~20%) amounts of phosphorylated heterocycles
      3a-c and 10a-c. Further treatment of bromo-substituted bicyclic systems 12a-c
      with the corresponding carbanion proceeded as a substitution of bromine for the
      residue of the Horner-Emmons reactant to afford compounds 13a-c bearing endo- and
      exocyclic phosphorus atoms. Reaction of diethyl vinylphosphonate with 5
      methylfuran 1 and 5-bromothiophene 9 provided spirofuran 8 as a sole reaction
      product and (5H-thieno[3,2-d]oxaphosphinin-2-yl)vinylphosphonate 15,
      respectively. Among the products, at 50 mg/kg dose, 4 compounds showed notable
      anti-inflammatory activity without toxicity side-effect.

PMID- 20817326
TI  - Synthesis and in vitro study of pseudo-peptide thioureas containing alpha
      aminophosphonate moiety as potential antitumor agents.
AB  - Twenty pseudo-peptide thioureas IIa-l containing alpha-aminophosphonate moiety
      were synthesized from the reaction of chiral alpha-amino carboxamide derivatives
      Ia-c with O,O'-dialkylisothiocyanato(phenyl)methylphosphonate 5. The synthesized
      compounds were completely characterized by elemental analysis, physical and
      spectral (IR, (1)H NMR, (13)C NMR) data. According to the preliminary studies on
      antitumor activities, compounds IIa-l could inhibit tumor cells PC3, Bcap37 and
      BGC823. These compounds displayed low to high activity by MTT assays. Among them,
      L-IIk, D-IIa and D-IIe were identified as potent inhibitors, with IC(50) values
      ranging from 4.7 to 11.2 MUM according to in vitro assay.

PMID- 20817325
TI  - Synthesis and characterization of a iodine-125-labeled pyrrolo[1,2-a]thieno[3,2
      e]pyrazine and evaluation as a potential 5-HT4R SPECT tracer.
AB  - In the aim to find new radiotracers for the in vivo imaging of 5-HT(4) receptors
      by ultra-high resolution quantitative SPECT, we have developed the synthesis of a
      radioiodinated 5-HT(4) ligand using an iododestannylation procedure. The [(125)I]
      ligand was obtained in a high radiochemical yield. Preliminary autoradiographic
      and ex vivo studies failed to show a specific labeling of 5-HT(4) receptors.

PMID- 20817327
TI  - Synthesis and cytotoxicity evaluation of 1-[3-(9H-carbazol-4-yloxy)-2
      hydroxypropyl]-3-aryl-1H-pyrazole-5-carboxylic acid derivatives.
AB  - Several novel molecules, 1-(3'-(9H-carbazol-4-yloxy)-2'-hydroxypropyl)-3-aryl-1H
      pyrazole-5-carboxylic acid derivatives 3a-g were synthesized and screened to
      evaluate their cytotoxicity against cancer cells in vitro. The compounds 3a-g has
      been prepared by the reaction of ethyl 3-aryl-1H-pyrazole-5-carboxylate with 4
      oxiranylmethoxy-9H-carbazole in moderate to excellent yields. The cytotoxicity of
      synthesized compounds was evaluated by a SRB (sulforhodamine B) assay against
      cancer cell such as SK-N-SH human neuroblastoma (NB), human A549 lung carcinoma,
      human breast cancer MCF-7 cell lines. The results showed that seven compounds can
      suppress SK-N-SH tumor cancer cell growth. Among them, compound 3d was the most
      effective small molecule in inhibiting SK-N-SH cell growth.

PMID- 20817328
TI  - Design, synthesis and biological evaluation of 1,3,4-oxadiazole derivatives.
AB  - 3D QSAR analysis for the 21 molecules of 1,3,4-oxadiazoles was carried out by
      using k-Nearest Neighbor Molecular Field Analysis (kNN-MFA) combined with various
      selection procedures. 30 3D QSAR models were generated; one of these models was
      selected on the basis of q(2) and pred_r(2) values. The selected Model has
      training set of 17 molecules and test set of 4 molecules with validation (q(2))
      and cross validation (pred_r(2)) values of 0.6969 and 0.6148 respectively. Title
      compounds of 1,3,4-oxadiazole derivatives were synthesized by the ring closure
      reactions of various acylhydrazides with carbon disulphide (4a-e) and with
      aromatic acids in POCl(3) (5a-e). After structural elucidation, all the
      synthesized compounds were evaluated for their antimicrobial activity against
      Escherichia coli, Staphylococcus aureus and Staphylococcus epidermidis.

PMID- 20817329
TI  - Synthesis, analgesic and anti-inflammatory evaluation of some novel quinazoline
      derivatives.
AB  - Two series of some new 2,4,6-trisubstituted-quinazoline derivatives were prepared
      and screened for their analgesic, anti-inflammatory activity and acute toxicity.
      Four compounds were more potent analgesic agents than the reference drug
      Indomethacin and thirteen compounds showed significant anti-inflammatory
      activity. Seven compounds showed combined ability to inhibit both pain and
      inflammation. Compounds tested for acute toxicity showed no toxic symptoms or
      mortality rates 24 h post-administration implying their good safety margin.

PMID- 20817330
TI  - Development of 3-aryl-1-isoquinolinamines as potent antitumor agents based on
      CoMFA.
AB  - Various substituted 3-aryl-1-isoquinolinamines were designed and synthesized
      based on the previously constructed CoMFA model. Most of the synthesized
      compounds showed excellent potency in eight different human tumor cell lines as
      expected. In order to find the exact cytotoxic mechanism of these 3-aryl-1
      isoquinolinamines, we analyzed the cell cycle dynamics by flow cytometry and
      found that 3-aryl-1-isoquinolinamine 6k-treated HeLa cells were arrested in G2/M
      phase, which is related to apoptosis.

PMID- 20817331
TI  - DNA binding, antioxidant and antimicrobial activities of homo- and heteronuclear
      copper(II) and nickel(II) complexes with new oxime-type ligands.
AB  - Some homo- and heteronuclear Cu(II) and Ni(II) complexes of new oxime-type
      ligands were tested against several pathogenic microorganisms to assess their
      antimicrobial potentials. The antimicrobial activities of complexes were
      evaluated in terms of minimum inhibitory concentration (MIC; MUg/MUL) and it was
      observed that the complexes possess moderate antimicrobial properties. The
      binding of the complexes with DNA were also investigated by using UV-Vis
      spectroscopy. It was seen that three of the complexes could bind to DNA through
      an intercalative mode while the other complexes could have other mechanisms.
      Furthermore, the antioxidant efficiencies of the metal complexes were determined
      by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radical scavening
      activities. Due to the observed IC(50) values, they are potential drugs to
      eliminate the radicals.

PMID- 20817332
TI  - A comparison of competencies between problem-based learning and non-problem-based
      graduate nurses.
AB  - Competence is essential to ensuring safe, ethical and legal nursing practice.
      Various teaching strategies are used in nursing education in an effort to enhance
      graduate competence by bridging the gap between theory learned in the classroom
      and professional practice as a nurse. The objective of this comparative
      descriptive research was to determine if there was a difference in self reported
      competence between graduates from PBL and non PBL (NPBL) nursing programs. A
      convenience sample of 121 graduate nurses in one Canadian province, who had been
      practicing for at least 6 months took part in the study. The researcher designed
      questionnaire included both forced choice and open ended questions. There was no
      statistical significance difference between the PBL and NPBL graduates on self
      reported entry-to-practice competence. However, several significant themes did
      emerge from the answers to open ended questions which asked graduates how their
      nursing programs prepared them to meet the entry-to-practice competencies and
      what program improvements they might suggest. Unlike the NPBL graduates, the PBL
      graduates identified the structure and process of their programs as instrumental
      in their preparation to meet the entry-to-practice competencies. PBL graduates
      associated their abilities to think critically and engage in self-directed
      evidence-based practice as key to enabling them to meet the competencies. A
      common theme for program improvement for both PBL and NPBL graduates was a
      request for more clinical time.

PMID- 20817333
TI  - Thrombohemorrhagic complications of myeloproliferative disorders.
AB  - Myeloproliferative disorders are commonly associated with thrombohemorrhagic
      manifestations. The current review highlights recent advances in understanding
      the epidemiology and pathogenetic mechanisms of thrombotic and bleeding
      complications. Therapeutic modalities and prophylactic interventions
      corresponding to the specific disease states are also discussed.

PMID- 20817334
TI  - Understanding depressive rumination from a cognitive science perspective: the
      impaired disengagement hypothesis.
AB  - Persisting negative thoughts are considered a hallmark of depression. Recent
      information-processing approaches have begun to uncover underlying mechanisms of
      depressive rumination. Despite marked advances in this area, there is a lack of
      integration between psychopathology and cognitive (neuro) science research. We
      propose the 'impaired disengagement' hypothesis as a unifying framework between
      both approaches. The core tenet of our model is that prolonged processing of self
      referent material is due to impaired attentional disengagement from negative self
      referent information. We discuss empirical evidence for this framework and
      outline future ways in which the causal predictions of this model can be tested.
      The proposed framework can account for effectiveness of various treatments for
      depression and may aid in devising new interventions to target depressive
      cognition.

PMID- 20817335
TI  - Eating disorders and quality of life: a review of the literature.
AB  - Following recent scientific interest in the quality of life (QoL) of individuals
      with eating disorders (EDs), this paper aims to provide a summary of the relevant
      evidence. A literature review on QoL in EDs (EDQoL) was carried out and relevant
      articles are described in six main sections. Following an introduction to the
      area and a summary of the methods used in the review, assessment of QoL in EDs is
      discussed. The third section represents the body of the review and appraises
      EDQoL in more detail, discussing what idiosyncratic features of EDs might be
      important in affecting QoL. The review concludes with suggestions for further
      research in this evolving area and summarizes the main findings. An evidence base
      is constructed supporting the idea that those with EDs have impaired QoL compared
      to other psychiatric and physical health conditions. However, what determines
      impairments in QoL is yet to be delineated although ideas for such variables,
      such as the presence of bingeing and purging, are suggested. Development of ED
      specific measures has aided greatly in the pursuit of clarity, although equivocal
      conclusions in this complex area necessitate further research.

PMID- 20817337
TI  - Differences between trait fear and trait anxiety: implications for
      psychopathology.
AB  - Fear and anxiety are poorly delineated in much of the clinical and research
      literatures. Although some theorists and researchers have posited explanations
      for how trait fear and trait anxiety differ, many others conceptualize the
      constructs as largely or entirely interchangeable. The primary goals of this
      review are to examine clinical conceptualizations and neurobiological studies of
      fear and anxiety, examine the animal and human literatures on the correlates of
      fear and anxiety, provide clearer definitions of these two constructs, and
      discuss their implications for psychopathology. A secondary goal is to evaluate
      content of self-report measures of trait fear and anxiety, and meta-analyze the
      relations between self-reported trait fear and anxiety. We found that existing
      measures share significant content overlap across constructs. Despite this
      overlap, our meta-analysis revealed only a moderate (r=0.32) relationship between
      measures of trait fear and anxiety, with an even lower relationship (r=0.14) when
      we examined trait fear measures operationalized in terms of harm avoidance. These
      findings suggest that fear and anxiety are largely distinct emotions, and that
      psychological disorders of trait fear and trait anxiety warrant classification in
      separate higher-order categories. Moreover, they suggest that future research
      should focus on deriving more content valid measures of trait fear and trait
      anxiety from the neurobiological and diagnostic literatures.

PMID- 20817336
TI  - Relationship between social anxiety disorder and body dysmorphic disorder.
AB  - Social anxiety disorder (SAD) and body dysmorphic disorder (BDD) are two
      separate, but conceptually overlapping nosological entities. In this review, we
      examine similarities between SAD and BDD in comorbidity, phenomenology, cognitive
      biases, treatment outcome, and cross-cultural aspects. Our review suggests that
      SAD and BDD are highly comorbid, show a similar age of onset, share a chronic
      trajectory, and show similar cognitive biases for interpreting ambiguous social
      information in a negative manner. Furthermore, research from treatment outcome
      studies have demonstrated that improvements in SAD were significantly correlated
      with improvements in BDD. Findings from cross-cultural research suggest that BDD
      may be conceived as a subtype of SAD in some Eastern cultures. Directions for
      future research and clinical implications of these findings are discussed.

PMID- 20817338
TI  - Latent inhibition is affected by phase of estrous cycle in female rats.
AB  - Estrogen has been shown to have a strong modulatory influence on several types of
      cognition in both women and female rodents. Latent inhibition is a task in which
      pre-exposure to a neutral stimulus, such as a tone, later impedes the association
      of that stimulus with a particular consequence, such as a shock. Previous work
      from our lab demonstrates that high levels of estradiol (E2) administered to
      ovariectomized (OVX) female rats abolishes latent inhibition when compared to
      female rats with low levels of E2 or male rats. To determine if this E2-induced
      impairment also occurs with the natural variations of ovarian hormones during the
      estrous cycle, this behavior was investigated in cycling female rats. In
      addition, pre-pubertal male and female rats were also tested in this paradigm to
      determine if the previously described sex differences are activational or
      organizational in nature. In a latent inhibition paradigm using a tone and a
      shock, adult rats were conditioned during different points of the estrous cycle.
      Rats conditioned during proestrus, a period of high E2 levels, exhibited
      attenuated latent inhibition when compared to rats conditioned during estrus or
      metestrus, periods associated with low levels of E2. Moreover, this effect is not
      seen until puberty indicating it is dependent on the surge of hormones at
      puberty. This study confirms recent findings that high E2 interferes with latent
      inhibition and is the first to show this is based in the activational actions of
      hormones.

PMID- 20817339
TI  - Moving from transcriptional to phospho-evolution: generalizing regulatory
      evolution?
AB  - Much of biological diversity is thought to arise from changes in regulatory
      networks. Although the role of transcriptional regulation has been well
      established, the contribution to evolution of changes at other levels of
      regulation has yet to be addressed. Using examples from the literature and recent
      studies on the evolution of protein phosphorylation, we argue that protein
      regulatory networks also play a prime role in generating diversity within and
      between species. Because there are several analogies between the regulation of
      protein functions by kinases and the regulation of gene expression by
      transcription factors, the principles that guide transcriptional regulatory
      evolution can also be explored in kinase-substrate networks. These comparisons
      will allow us to generalize existing models of evolution across the complex
      layers of the cell's regulatory links.

PMID- 20817340
TI  - Lung cancer clinicians' preferences for adjuvant chemotherapy in non-small-cell
      lung cancer: what makes it worthwhile?
AB  - AIMS: We sought (i) lung cancer clinicians' judgements about the smallest
      survival benefits that would make the harms of adjuvant chemotherapy for non
      small-cell lung cancer (NSCLC) worthwhile, (ii) factors associated with their
      judgements, and (iii) comparisons with breast cancer and colon cancer clinicians
      surveyed similarly in 2002-2003. METHODS: Delegates at the Australian Lung Cancer
      Conference 2008 were invited to complete a validated, self-administered
      questionnaire that used the time trade-off method to determine the minimum
      survival benefits judged sufficient to make adjuvant chemotherapy worthwhile. The
      baseline survival times were 3 and 5 years, and the baseline 5-year survival
      rates were 50% and 65%. Chemotherapy was 4 cycles of cisplatin and vinorelbine.
      RESULTS: Characteristics of the 156 respondents were: median age 41 years (range
      23-62), female 55%, married 83%, with dependent children 62%, respiratory
      physician 28%, nurse 24%, medical oncologist 14%, radiation oncologist 12%, trial
      nurse/coordinator 12%, thoracic surgeon 4%. Moderate survival benefits were
      judged sufficient to make chemotherapy worthwhile. The median benefit judged
      sufficient was an extra 9 months beyond a baseline survival time of 3 or 5 years.
      The median benefit judged sufficient was an extra 5% for a baseline survival rate
      of 65%, versus an extra 10% for a baseline survival rate of 50% (p<0.001).
      Smaller benefits were judged sufficient by clinicians who were married (p=0.02)
      or had dependants (p=0.04). Lung cancer clinicians judged smaller benefits
      sufficient than breast cancer (n=89) and colon cancer (n=72) clinicians in
      similar prior studies (median required benefit of 9 months versus 12 months,
      p<0.001). CONCLUSION: Most lung cancer clinicians attending a national lung
      cancer conference judged moderate improvements in survival sufficient to make
      adjuvant chemotherapy worthwhile. Smaller benefits were judged sufficient by lung
      cancer clinicians in 2008 than by breast cancer and colon cancer clinicians 5-6
      years earlier. Clinicians should be aware of their own preferences, and explore
      their patients' preferences, when discussing adjuvant chemotherapy.

PMID- 20817341
TI  - PKC-delta signalling pathway is involved in H9c2 cells differentiation.
AB  - H9c2 are rat heart embryonic myoblasts, with skeletal muscle properties, which
      terminally differentiate by fusing and forming multinucleated myotubes. Here we
      investigated the possible involvement of Protein Kinases C (PKCs) in H9c2 cell
      differentiation and explored the interplay of these enzymes both with reactive
      oxygen species (ROS), upstream physiological mediators of cell differentiation,
      and with nitric oxide (NO), downstream target of PKC activation, known for being
      involved in apoptosis induction in differentiated myoblasts. Cells were induced
      to differentiate (6 days) under low serum culture conditions and assayed for the
      expression of cell cycle (cyclin A) and differentiation markers (morphology and
      myogenin). Both ROS and in vivo production of NO were found increased after 6
      days of differentiation, when the activation of PKC-delta isoform was 14-fold
      increased compared with the undifferentiated control cells. The parallel analysis
      of apoptotic features demonstrated a small increase in Annexin-V+ cells and a
      concomitant increase in PARP cleavage and Bax expression. Interestingly, a
      reduced percentage of differentiated cells was obtained both in the presence of
      Rottlerin, a highly selective PKC-delta pharmacologic inhibitor, and, moreover,
      with the use of PKC-delta siRNA technology, further supporting the involvement of
      PKC-delta in switching on the events related to skeletal muscle myoblast
      differentiation.

PMID- 20817342
TI  - The rbcL gene of Populus deltoides has multiple transcripts and is redox
      regulated in vitro.
AB  - We report the discovery of three types of transcripts for the gene encoding large
      subunit of Rubisco (rbcL) from chloroplast genome of Populus deltoides, an
      angiospermic tree. While the larger two transcripts are in confirmation with
      reported transcripts for other rbcL genes as far as the 5' ends are concerned,
      the third transcript is unique since it lacks the consensus ribosome-binding
      site. We also report the molecular weights of several proteins interacting with
      the 5' untranslated region of the same mRNA and that the RNA-protein interaction
      in vitro is influenced by redox reagents.

PMID- 20817343
TI  - Retroperitoneal lymph node dissection with no adjuvant chemotherapy in clinical
      stage I nonseminomatous germ cell tumours: long-term outcome and analysis of risk
      factors of recurrence.
AB  - BACKGROUND: The best management for patients with clinical stage I (CS1)
      nonseminomatous germ cell tumours (NSGCT) is still under debate. OBJECTIVE: We
      evaluated the long-term oncologic outcome of retroperitoneal lymph node
      dissection (RPLND) in patients with CS1 NSGCTs and reevaluated the traditional
      predictors of recurrence in a set of patients not undergoing adjuvant treatment.
      DESIGN, SETTING, AND PARTICIPANTS: Between 1985 and 1995, 322 consecutive CS1
      NSGCT patients underwent primary RPLND not followed by adjuvant chemotherapy in a
      single referral centre. Patients were followed until relapse for a median time of
      17 yr. MEASUREMENTS: We estimated the crude cumulative incidence of any
      recurrence. Categories pN and pT, vascular invasion (VI), percentage of embryonal
      carcinoma, and presence of teratoma were evaluated as 2-yr recurrence predictors
      of event in a binary logistic model. RESULTS AND LIMITATIONS: Fifty patients had
      a recurrence (46 in <= 2 yr and only 4 [1.2%] in > 2 yr). The 10-yr recurrence
      incidence was 15.2%. Significant predictors of recurrence at multivariable
      analysis were pN+, pT > 1, and the presence of VI. However, the discriminative
      ability of the model was modest (Harrell C = 0.74); only 9% and 3% of patients
      had a predicted recurrence probability > 30% and > 50%, respectively.
      CONCLUSIONS: RPLND alone could prevent recurrence in 85% of patients and minimise
      late relapses to 1.2%. Most patients could avoid the immediate and late toxicity
      of chemotherapy. Prognostic parameters combined into the multivariable model
      appeared of limited use in identifying a subset of patients at high risk of
      recurrence.

PMID- 20817344
TI  - [Crystalline lens photodisruption using femtosecond laser: experimental study].
AB  - PURPOSE: The aim of this study was to analyze the interactions during femtosecond
      (fs) laser photodisruption in ex vivo porcine crystalline lenses and to study the
      parameters for laser interaction optimization. METHODS: An experimental
      femtosecond laser was used. The laser characteristics were: 1030 nm wavelength;
      pulse duration, 400 fs; and numerical aperture, 0.13. Specific software was
      created to custom and monitor any type of photoablation pattern for treatment
      purposes. Porcine crystalline lenses were placed in an open sky holder filled
      with physiological liquid (BSS) covered by a glass plate. A numerical camera was
      associated with metrological software in order to magnify and quantify the
      results. Transmission electron microscopy (TEM) was performed on some samples to
      identify the microscopic plasma interactions with the lens. The optimization of
      parameters was investigated in terms of the optical breakdown threshold, the
      sizing of interactions, and the best pattern for alignments. More than 150
      crystalline lenses of freshly enucleated pigs were treated. RESULTS: The optical
      breakdown threshold (OBT) was defined as the minimal energy level per pulse
      necessary to observe a physical interaction. In our study, the OBT varied
      according to the following parameters: the crystalline lens itself, varying from
      4.2 to 7.6 MUJ (mean, 5.1 MUJ), and the depth of laser focus, varying up to 1
      MUJ, increasing in the depth of the tissue. Analyzing the distance between
      impacts, we observed that the closer the impacts were the less power was needed
      to create a clear well-drawn defect pattern (lines), i.e., with a 4-MUJ optimized
      OBT, when the impacts were placed every 2 MUm for the x,y directions and 60 MUm
      for the z direction. Coalescent bubbles created by plasma formation always
      disappeared in less than 24h. The nonthermal effect of plasma and the
      innocuousness on surrounding tissues were proven by the TEM results. DISCUSSION:
      The crystalline lens photodisruption by the femtosecond laser seems an innovative
      technique usable in the ultra precise crystalline lens cutting. Experimental
      studies in vivo are necessary in order to define of them the applications
      (surgery of the cataract and presbyopia) and limits in the cavitations bubbles
      kinetic and transfer.

PMID- 20817345
TI  - Chemical speciation of respirable suspended particulate matter during a major
      firework festival in India.
AB  - Ambient respirable particles (PM <= 10 MUm, denoted by PM(10)) were characterized
      with respect to 20 elements, 16 polycyclic aromatic hydrocarbons (PAHs),
      elemental and organic carbon (EC and OC) during a major firework event-the
      "Diwali" festival in Delhi, India. The event recorded extremely high 24-h PM(10)
      levels (317.2-616.8 MUg m(-3), 6-12 times the WHO standard) and massive loadings
      of Ba (16.8 MUg m(-3), mean value), K (46.8 MUg m(-3)), Mg (21.3 MUg m(-3)), Al
      (38.4 MUg m(-3)) and EC (40.5 MUg m(-3)). Elemental concentrations as high as
      these have not been reported previously for any firework episode. Concentrations
      of Ba, K, Sr, Mg, Na, S, Al, Cl, Mn, Ca and EC were higher by factors of 264, 18,
      15, 5.8, 5, 4, 3.2, 3, 2.7, 1.6 and 4.3, respectively, on Diwali as compared to
      background values. It was estimated that firework aerosol contributed 23-33% to
      ambient PM(10) on Diwali. OC levels peaked in the post-Diwali samples, perhaps
      owing to secondary transformation processes. Atmospheric PAHs were not sourced
      from fireworks; instead, they correlated well with changes in traffic patterns
      indicating their primary source in vehicular emissions. Overall, the pollutant
      cocktail generated by the Diwali fireworks could be best represented with Ba, K
      and Sr as tracers. It was also found that chronic exposure to Diwali pollution is
      likely to cause at least a 2% increase in non-carcinogenic hazard index (HI)
      associated with Al, Mn and Ba in the exposed population.

PMID- 20817346
TI  - Adsorption of cadmium from aqueous solution onto untreated coffee grounds:
      equilibrium, kinetics and thermodynamics.
AB  - Adsorption can be used as a cost effective and efficient technique for the
      removal of toxic heavy metals from wastewater. Waste materials with no further
      treatment such as coffee grounds from cafeterias may act as adsorbents for the
      removal of cadmium. Batch kinetic and equilibrium experiments were conducted to
      study the effects of contact time, adsorbent dose, initial pH, particle size,
      initial concentration of cadmium and temperature. Three adsorption isotherm
      models namely, Langmuir, Freundlich and Dubinin-Radushkevich were used to analyse
      the equilibrium data. The Langmuir isotherm which provided the best correlation
      for Cd(2+) adsorption onto coffee grounds, shows that the adsorption was
      favourable and the adsorption capacity found was equal to 15.65 mg g(-1).
      Thermodynamic parameters were evaluated and the adsorption was exothermic. The
      equilibrium was achieved less than 120 min. The adsorption kinetic data was
      fitted with first and second order kinetic models. Finally it was concluded that
      the cadmium adsorption kinetic onto coffee grounds was well fitted by second
      order kinetic model rather than first order model. The results suggest that
      coffee grounds have high possibility to be used as effective and economical
      adsorbent for Cd(2+) removal.

PMID- 20817347
TI  - Adsorption of uranium from aqueous solution using chitosan-tripolyphosphate
      (CTPP) beads.
AB  - Chitosan-tripolyphosphate (CTPP) beads were prepared using in-liquid curing
      method and used for the adsorption of uranium from aqueous solution. Beads were
      prepared at two different cross-linking densities by adjusting the pH of the
      tripolyphosphate solution. The synthesized beads were characterized using FTIR
      spectroscopy before and after adsorption of uranium. Beads having higher cross
      linking are found to have better adsorption capacity for uranium. Factors that
      influence the uranium adsorption onto CTPP beads such as solution pH, contact
      time and initial uranium concentration were studied in detail. The experimental
      results were fitted into Langmuir and Freundlich adsorption isotherms. From
      Langmuir adsorption model the adsorption capacity of CTPP beads for uranium is
      estimated as 236.9 mg/g. Pseudo-first order, pseudo-second order and
      intraparticle diffusion model were applied to the observed kinetics data and the
      results shows that the pseudo-second order model is more suitable to explain the
      kinetics of adsorption of uranium on CTPP beads. FTIR spectroscopic
      characterization of the beads showed that the phosphate groups may be more
      responsible for the adsorption of uranium on CTPP beads.

PMID- 20817348
TI  - Systemic loxoscelism in the age of community-acquired methicillin-resistant
      Staphylococcus aureus.
AB  - The increase in cases of community-acquired methicillin-resistant Staphylococcus
      aureus (MRSA), as well as its isolation from the majority of skin and soft tissue
      abscesses in the emergency department, requires the emergency physician to
      consider this diagnosis in all skin or soft tissue infections. However, making
      the diagnosis of MRSA when the wound is actually a cutaneous lesion of a brown
      recluse spider bite may have untoward consequences. Furthermore, the clinical
      manifestations of systemic loxoscelism may be misdiagnosed as a systemic
      staphylococcal infection. We present a patient with systemic loxoscelism who was
      diagnosed with a systemic infection and received an unnecessary surgical
      procedure.

PMID- 20817349
TI  - Emergency management of a traumatic tooth avulsion.
AB  - Emergency department visits for dental complaints are a common occurrence, and
      tooth avulsion is one of the most serious of these presentations. In this case
      report, we describe the use of 2-octyl cyanoacrylate and a pliable metal nasal
      bridge from a respirator mask to replant the tooth and stabilize it during the
      patient's clinical course. Reassessment of the tooth confirmed that successful
      replantation had been accomplished. Given the limitations of a single case
      report, the described method of tooth replantation may be a useful approach that
      emergency medicine practitioners may add to their dental emergency repertoire.

PMID- 20817350
TI  - Transferrin and HFE genes interact in Alzheimer's disease risk: the Epistasis
      Project.
AB  - Iron overload may contribute to the risk of Alzheimer's disease (AD). In the
      Epistasis Project, with 1757 cases of AD and 6295 controls, we studied 4 variants
      in 2 genes of iron metabolism: hemochromatosis (HFE) C282Y and H63D, and
      transferrin (TF) C2 and -2G/A. We replicated the reported interaction between HFE
      282Y and TF C2 in the risk of AD: synergy factor, 1.75 (95% confidence interval,
      1.1-2.8, p = 0.02) in Northern Europeans. The synergy factor was 3.1 (1.4-6.9;
      0.007) in subjects with the APOEepsilon4 allele. We found another interaction,
      between HFE 63HH and TF -2AA, markedly modified by age. Both interactions were
      found mainly or only in Northern Europeans. The interaction between HFE 282Y and
      TF C2 has now been replicated twice, in altogether 2313 cases of AD and 7065
      controls, and has also been associated with increased iron load. We therefore
      suggest that iron overload may be a causative factor in the development of AD.
      Treatment for iron overload might thus be protective in some cases.

PMID- 20817351
TI  - Early temporal short-term memory deficits in double transgenic APP/PS1 mice.
AB  - We tested single APP (Tg2576) transgenic, PS1 (PS1dE9) transgenic, and double
      APP/PS1 transgenic mice at 3 and 6 months of age on the acquisition of a
      hippocampal-dependent operant "differential reinforcement of low rate schedule"
      (DRL) paradigm. In this task mice are required to wait for at least 10 seconds
      (DRL-10s) between 2 consecutive nose poke responses. Our data showed that while
      single APP and PS1 transgene expression did not affect DRL learning and
      performance, mice expressing double APP/PS1 transgenes were impaired in the
      acquisition of DRL-10s at 6 months, but not at 3 months of age. The same impaired
      double transgenic mice, however, were perfectly capable of normal acquisition of
      signaled DRL-10s (SDRL-10s) task, a hippocampal-independent task, wherein mice
      were required to emit responses when the end of the 10-second delay was signaled
      by a lighting of the chamber. The age-dependent and early deficits of APP/PS1
      mice suggest that the appetitive DRL paradigm is sensitive to the amyloid
      pathology present in double APP/PS1 mice, and that this mouse line represents a
      good model with which to study the efficacy of therapeutic strategies against
      Alzheimer's disease.

PMID- 20817352
TI  - Issues to ponder when correlating hippocampal neurogenesis to a hippocampal
      dependent memory function.
AB  - Simple correlations between the overall hippocampal neurogenesis and the
      hippocampal-dependent learning and memory functions are common in the
      neurogenesis field. There is considerable evidence in the literature to link
      hippocampal neurogenesis to the hippocampal-dependent memory function. However,
      simple correlations between neurogenesis and memory function, particularly in
      studies where neither the cause-effect relationship is established nor the other
      relevant variables are considered, can lead to erroneous conclusions. As reliable
      and selective neurogenesis ablation techniques are yet to be developed for rat
      and higher animal models, it is likely that correlative studies between the
      overall neurogenesis and the memory function will continue in different
      conditions in these animal models. Such correlations should be acceptable as long
      as the other variables are considered adequately. Furthermore, in correlative
      analyses of the learning and memory function with the newly born granule cells,
      one needs to consider the age of the newly born granule cells because the newly
      born granule cells will require at least a few weeks of time after their birth to
      participate in the learning and memory function in rodent models.

PMID- 20817353
TI  - Populations of inhibitory and excitatory interneurons in lamina II of the adult
      rat spinal dorsal horn revealed by a combined electrophysiological and anatomical
      approach.
AB  - Lamina II contains a large number of interneurons involved in modulation and
      transmission of somatosensory (including nociceptive) information. However, its
      neuronal circuitry is poorly understood due to the difficulty of identifying
      functional populations of interneurons. This information is important for
      understanding nociceptive processing and for identifying changes that underlie
      chronic pain. In this study, we compared morphology, neurotransmitter content,
      electrophysiological and pharmacological properties for 61 lamina II neurons
      recorded in slices from adult rat spinal cord. Morphology was related to
      transmitter content, since islet cells were GABAergic, while radial and most
      vertical cells were glutamatergic. However, there was considerable diversity
      among the remaining cells, some of which could not be classified morphologically.
      Transmitter phenotype was related to firing pattern, since most (18/22)
      excitatory cells, but few (2/23) inhibitory cells had delayed, gap or reluctant
      patterns, which are associated with A-type potassium (I(A)) currents.
      Somatostatin was identified in axons of 14/24 excitatory neurons. These had
      variable morphology, but most of those tested showed delayed-firing. Excitatory
      interneurons are therefore likely to contribute to pain states associated with
      synaptic plasticity involving I(A) currents. Although noradrenaline and serotonin
      evoked outward currents in both inhibitory and excitatory cells, somatostatin
      produced these currents only in inhibitory neurons, suggesting that its pro
      nociceptive effects are mediated by disinhibition. Our results demonstrate that
      certain distinctive populations of inhibitory and excitatory interneuron can be
      recognised in lamina II. Combining this approach with identification of other
      neurochemical markers should allow further clarification of neuronal circuitry in
      the superficial dorsal horn.

PMID- 20817354
TI  - Brain correlates of stress-induced analgesia.
AB  - Stress-induced analgesia (SIA) refers to a reduced pain response after stress
      exposure, which is mediated by descending pain-inhibitory circuits and may be an
      indicator of adequate centrally mediated pain control. We used functional
      magnetic resonance imaging to assess brain mechanisms of SIA in 21 healthy
      participants. Using a block design series of mildly painful pressure stimuli were
      applied to the left medial phalanx of the second digit during functional magnetic
      resonance imaging. Mental arithmetic combined with increasing levels of noise was
      used as a stressor. Verbal ratings, changes in blood pressure and heart rate
      confirmed the validity of the stress induction. Post-stress pain thresholds and
      pain tolerance were significantly higher and post-stress pain and unpleasantness
      ratings were significantly lower compared to pre-stress levels. SIA led to an
      increase of the blood-level-dependent oxygenation response in the primary
      somatosensory cortex, bilaterally in the anterior insula, and secondary
      somatosensory cortex. The increase in pain tolerance correlated significantly
      with activation in the rostral anterior cingulate cortex and pain unpleasantness
      with activation in the dorsal anterior cingulate cortex. SIA seems to activate
      similar brain networks as placebo analgesia or analgesia mediated by diffuse
      noxious inhibitory controls and involved sensory, affective and cognitive
      modulatory circuits.

PMID- 20817356
TI  - Topographical differences in distribution and responsiveness of trigeminal
      sensitivity within the human nasal mucosa.
AB  - The study was designed to provide a topographical map of the sensitivity of the
      human nasal respiratory epithelium towards trigeminal chemosensory stimuli. As an
      electrophysiological measure of intranasal trigeminal activation at the level of
      the epithelium, we used the so-called negative mucosa potential (NMP), a measure
      that represents the sum of generator potentials of trigeminal receptor neurons
      after chemical stimulation. Sixty subjects participated (30 men and 30 women;
      mean age 23.5 years). Measurements were made in response to stimulation with
      menthol, CO(2), ethanol, and cinnamaldehyde, which are known to activate
      trigeminal receptors to various degrees. Recordings of the NMP were made from
      five intranasal sites: the anterior septum, the posterior septum, the tip of the
      middle turbinate, the tip of the lower turbinate, and the lateral side wall of
      the posterior nasal cavity. The recording electrode was positioned under
      endoscopic control. The largest NMP amplitudes were recorded at the anterior
      septum in response to stimulation with CO(2). Comparing all recording sites,
      significant differences were observed between responses at the posterior septum
      and the lateral side wall of the posterior nasal cavity in response to
      stimulation by ethanol, menthol, and CO(2). These findings suggest that the
      presence of topographical and chemosensory differences in the responsiveness of
      the nasal mucosa to irritants.

PMID- 20817357
TI  - Prudent use of antimicrobials: have we done the best we can? The SEIMC and REIPI
      statement.

PMID- 20817355
TI  - How the number of learning trials affects placebo and nocebo responses.
AB  - Conditioning procedures are used in many placebo studies because evidence
      suggests that conditioning-related placebo responses are usually more robust than
      those induced by verbal suggestions alone. However, it has not been shown whether
      there is a causal relation between the number of conditioning trials and the
      resistance to extinction of placebo and nocebo responses. Here we test the
      effects of either one or four sessions of conditioning on the modulation of both
      non-painful and painful stimuli delivered to the dorsum of the foot. Placebo and
      nocebo manipulations were obtained by pairing green or red light to a series of
      stimuli that were made lower or higher with respect to a yellow light associated
      with a series of control stimuli. Subjects were told that the lights would
      indicate a treatment that would reduce or increase non-painful and painful
      stimuli to the foot. They were randomly assigned to either Group 1 or 2. Group 1
      underwent one session of conditioning and Group 2 received four sessions of
      conditioning. We found that one session of conditioning (Group 1) induced nocebo
      responses, but not placebo responses in no pain condition. After one session of
      conditioning, we observed both nocebo and placebo responses to painful
      stimulation. However, these effects extinguished over time. Conversely, four
      sessions of conditioning (Group 2) induced robust placebo and nocebo responses to
      both non-painful and painful stimuli that persisted over the entire experiment.
      These findings suggest that the strength of learning may be clinically important
      for producing long-lasting placebo effects.

PMID- 20817358
TI  - Leishmaniasis in Spanish tattoos.

PMID- 20817359
TI  - [Emergence of paediatric infections due to community-associated methicillin
      resistant Staphylococcus aureus: should we sound the alarm?].

PMID- 20817361
TI  - Dicrocoelium dendriticum in cattle from Cypress Hills, Canada: humoral response
      and preliminary evaluation of an ELISA.
AB  - Apparent changes in the distribution of Dicrocoelium dendriticum in western
      Canada and the absence of other liver flukes in the area prompted an examination
      of the humoral responses in naturally infected cattle sharing pasture with
      heavily infected wild cervids. Western blots using sera from the infected cattle
      indicated that the cattle had antibodies to various fluke antigens, however the
      pattern of response varied among isotypes. Isotype analysis indicated that
      Dicrocoelium-infected cattle produced IgG1, and IgM antibodies, but not IgG2
      antibodies. Subsequent comparison of the efficiency of coprological and
      serological approaches for diagnosis showed that while 43.5% of a separate group
      of 26 yearlings had eggs in their faeces, the immunoblots indicated that all had
      detectable antibodies. A group of cattle necropsied for confirmation of fluke
      status was used to evaluate humoral immune responses and to provide baseline
      information in the preliminary development of an indirect ELISA for detection of
      anti-fluke antibodies.

PMID- 20817362
TI  - Exploring new inhibitors of Plasmodium falciparum purine nucleoside
      phosphorylase.
AB  - Plasmodium falciparum purine nucleoside phosphorylase (PfPNP) has a central role
      in purine salvage and inhibitors of the enzyme have been shown to have
      antiplasmodial activity. The enzyme preferentially uses inosine as substrate
      (K(m)=5 MUM, k(cat)/K(m)=7.4*10(4) M(-1) s(-1)), but can also use uridine, albeit
      less efficiently (K(m)=85 MUM, k(cat)/K(m)=306 M(-1) s(-1)). In an effort to
      identify new PfPNP inhibitors, two series of compounds were prepared. Series 1
      was based on known human uridine phosphorylase inhibitors whilst series 2 was
      uracil equivalents of purine-based PNP transition state inhibitors. These two
      series of compounds were assayed for inhibition of both PfPNP activity and growth
      of P. falciparum. The transition state analogues were found to be moderate
      inhibitors of PfPNP (most potent compound, K(i)=6 MUM).

PMID- 20817363
TI  - Plant/soil concentration ratios for paired field and garden crops, with emphasis
      on iodine and the role of soil adhesion.
AB  - In the effort to predict the risks associated with contaminated soils,
      considerable reliance is placed on plant/soil concentration ratio (CR) values
      measured at sites other than the contaminated site. This inevitably results in
      the need to extrapolate among the many soil and plant types. There are few
      studies that compare CR among plant types that encompass both field and garden
      crops. Here, CRs for 40 elements were measured for 25 crops from farm and garden
      sites chosen so the grain crops were in close proximity to the gardens. Special
      emphasis was placed on iodine (I) because data for this element are sparse. For
      many elements, there were consistent trends among CRs for the various crop types,
      with leafy crops > root crops >= fruit crops ~ seed crops. Exceptions included CR
      values for As, K, Se and Zn which were highest in the seed crops. The correlation
      of CRs from one plant type to another was evident only when there was a wide
      range in soil concentrations. In comparing CRs between crop types, it became
      apparent that the relationships differed for the rare earth elements (REE), which
      also had very low CR values. The CRs for root and leafy crops of REE converged to
      a minimum value. This was attributed to soil adhesion, despite the samples being
      washed, and the average soil adhesion for root crops was 500 mg soil kg-1 dry
      plant and for leafy crops was 5 g kg-1. Across elements, the log CR was
      negatively correlated with log Kd (the soil solid/liquid partition coefficient),
      as expected. Although, this correlation is expected, measures of correlation
      coefficients suitable for stochastic risk assessment are not frequently reported.
      The results suggest that r ~ -0.7 would be appropriate for risk assessment.

PMID- 20817364
TI  - All about KRAS for clinical oncology practice: gene profile, clinical
      implications and laboratory recommendations for somatic mutational testing in
      colorectal cancer.
AB  - The KRAS oncogene has been extensively studied for more than three decades,
      however, it is only recently that it attained a central role in the clinical
      decision-making process for the practicing oncologist. Recently, based on
      retrospective analyses of large randomized clinical trials, the use of anti
      epidermal growth factor (EGFR) monoclonal antibodies, cetuximab and panitumumab,
      was restricted to patients with metastatic colorectal cancer that carry the "wild
      type"KRAS genotype. Challenges remain in the laboratory implementation of KRAS
      mutational testing and the clinical application of the test for treatment
      planning. This review attempts to offer a global view of KRAS biology, its
      functional role in cell signaling, mechanisms of resistance to anti-EGFR agents
      and its predictive potential in metastatic colorectal cancer. We also survey the
      growing list of candidate biomarkers that may shortly supplement KRAS in routine
      clinical patient stratification. Finally, we discuss practical aspects of KRAS
      testing that may be useful for those involved in mutational screening in their
      centers. This general overview of KRAS for clinical oncology practice aims to
      assist in data interpretation and offer insight into potential pitfalls of
      mutational testing. KRAS is a prime example of how translational research can
      fulfill the promises of personalized medicine for tailoring treatment to match
      the underlying tumor biology.

PMID- 20817365
TI  - Biomechanical evaluation of double bundle augmentation of posterior cruciate
      ligament using finite element analysis.
AB  - BACKGROUND: Posterior cruciate ligament injuries commonly occur during sports
      activities or motor vehicle accidents. However, there is no previous comparison
      study of single bundle reconstruction, double bundle reconstruction, and double
      bundle augmentation with respect to biomechanical characteristics such as
      stability and ligament stress. METHODS: A three-dimensional finite element model
      of a lower extremity including femur, tibia, cartilage, meniscus, collagen
      fibers, and four major ligaments was developed and validated. In addition to the
      intact, posterior cruciate ligament injured, single bundle reconstruction, double
      bundle reconstruction, and double bundle augmentation models were developed.
      Then, the posterior and rotational tibial translations as well as the ligament
      stresses were predicted for 89 N posterior force and 3 Nm internal torque,
      respectively, in the normal (no secondary deficiency) and the secondary
      deficiency cases using finite element analysis. FINDINGS: The posterior stability
      and ligament stresses following double bundle augmentation were superior to those
      of single and double bundle reconstructions, especially after secondary
      deficiency in the reconstructed grafts, despite little difference in posterior
      stability between double bundle reconstruction and augmentation in the normal
      case. Similarly, the double bundle augmentation had the greatest rotational
      stability while there was little advantage in ligament stress compared to those
      of the other reconstruction method. INTERPRETATION: Double bundle augmentation
      has advantages with regard to posterior and rotational stabilities as well as
      ligament stress in comparison with other reconstruction methods, especially
      following secondary deficiencies in the reconstructed grafts.

PMID- 20817366
TI  - Anaemia of prematurity: pathophysiology and treatment.
AB  - Most infants with birth weight <1.0 kg are given multiple red blood cell (RBC)
      transfusions within the first few weeks of life. The anaemia of prematurity is
      caused by untimely birth occurring before placental iron transport and fetal
      erythropoiesis are complete, by phlebotomy blood losses taken for laboratory
      testing, by low plasma levels of erythropoietin due to both diminished production
      and accelerated catabolism, by rapid body growth and need for commensurate
      increase in red cell volume/mass, and by disorders causing RBC losses due to
      bleeding and/or hemolysis. RBC transfusions are the mainstay of therapy with
      recombinant human erythropoietin largely unused because it fails to substantially
      diminish RBC transfusion needs--despite exerting substantial erythropoietic
      effects on neonatal marrow.

PMID- 20817367
TI  - Alpha-2 agonists to reduce vasopressor requirements in septic shock?
AB  - One of the unsolved problems of septic shock is the poor responsiveness, or
      reduced vascular reactivity, to vasopressors used to increase blood pressure
      (BP). Attempts to restore vascular reactivity with NO inhibitors or low dose
      steroids have met with little success. Low vascular reactivity, which may lead to
      refractory shock and death, is linked to desensitization or down-regulation of
      alpha-1 adrenergic receptors. Our working hypothesis is that the use of alpha-2
      agonists (e.g. clonidine or dexmedetomidine) in septic shock, in addition to the
      state-of-the-art treatment (including volume load and vasopressors), will reduce
      the vasopressor requirements needed to restore adequate BP. This counter
      intuitive proposal is based on the fact that alpha-2 agonists will reduce the
      massive release of endogenous catecholamines. A decrease in plasma endogenous
      catecholamine concentrations will be followed by reduced down-regulation of alpha
      1 receptors and/or a gradual re-sensitization of alpha-1 adrenergic receptors. In
      turn, this will lead to lowered vasopressor requirement, with respect to dose and
      duration. Our hypothesis, based on a reverse "denervation hypersensitivity", is
      at variance with accepted treatments, which rest only on volume load and
      vasopressors and emphasizes restoration of blood pressure per se. Several
      observations in the cardiology and anesthesia setting have shown increased
      vascular reactivity following alpha-2 agonist administration. Our preliminary
      observations in the setting of septic shock again suggest such increased vascular
      reactivity. Improved outcome was also observed. Rigorous work is warranted to
      verify reduced vasopressor requirement and improved outcome, when an alpha-2
      agonist is combined with state-of -the-art treatment of septic shock.

PMID- 20817368
TI  - Depositional history of sedimentary linear alkylbenzenes (LABs) in a large South
      American industrial coastal area (Santos Estuary, Southeastern Brazil).
AB  - This paper reports the reconstruction of the contamination history of a large
      South American industrial coastal area (Santos Estuary, Brazil) using linear
      alkylbenzenes (LABs). Three sediment cores were dated by (137)Cs. Concentrations
      in surficial layers were comparable to the midrange concentrations reported for
      coastal sediments worldwide. LAB concentrations increased towards the surface,
      indicating increased waste discharges into the estuary in recent decades. The
      highest concentration values occurred in the early 1970s, a time of intense
      industrial activity and marked population growth. The decreased LAB
      concentration, in the late 1970s was assumed to be the result of the world oil
      crisis. Treatment of industrial effluents, which began in 1984, was represented
      by decreased LAB levels. Microbial degradation of LABs may be more intense in the
      industrial area sediments. The results show that industrial and domestic waste
      discharges are a historical problem in the area.

PMID- 20817369
TI  - Abiotic transformation of estrogens in synthetic municipal wastewater: an
      alternative for treatment?
AB  - The abiotic transformation of estrogens, including estrone (E1), estradiol (E2),
      estriol (E3) and ethinylestradiol (EE2), in the presence of model vegetable
      matter was confirmed in this study. Batch experiments were performed to model the
      catalytic conversion of E1, E2, E3 and EE2 in synthetic wastewater. Greater than
      80% reduction in the parent compounds was achieved for each target chemical after
      72h with the remaining concentration distributed between aqueous and solid phases
      as follows: 13% and 7% for E1, 10% and 2% for E2, 6% and 2% for E3, and 8% and 3%
      for EE2, respectively. Testosterone, androstenedione and progesterone were also
      monitored in this study, and their concentrations were found to be in agreement
      with initially spiked amount. Data collected under laboratory conditions provided
      the basis for implementing new abiotic wastewater treatment technologies that use
      inexpensive materials.

PMID- 20817370
TI  - Rapidly progressive severe vascular calcification sparing the kidney allograft
      following warfarin initiation.
AB  - We describe a case of rapid onset of vascular calcification coincident with the
      initiation of warfarin therapy in a kidney transplant recipient. Calcification
      developed within the media of the blood vessel wall, with relative intimal
      sparing. Medium and small arteries were affected; however, the aorta was mostly
      free of calcifications, suggesting a differential response to warfarin between
      the intima and media and between different vascular beds. In addition, unlike the
      highly calcified native kidney's vessels, the kidney allograft was not calcified,
      suggesting local genetically determined mechanisms in preventing vascular
      calcification. Distal subcutaneous necrosis ultimately led to the patient's
      death.

PMID- 20817371
TI  - Internalizing disorders and substance use disorders in youth: comorbidity, risk,
      temporal order, and implications for intervention.
AB  - This review examines the empirical literature on the relationship between
      internalizing disorders and substance use disorders (SUDs) in youth in terms of
      (a) comorbidity rates, (b) risk relationships, (c) temporal sequencing, and (d)
      implications for intervention. Findings from community and clinical samples
      suggest that comorbidity rates range from 9.0 to 47.9%. The majority of the
      evidence supports the temporal precedence of internalizing disorders before
      substance use disorders and a unidirectional risk model in which internalizing
      disorders increase risk for later substance use disorders. Implications of this
      relationship for interventions are considered, both in terms of treatment outcome
      for principal disorders and in terms of the potential "secondary benefit" of
      treating one disorder for preventing or reducing risk of the other. Finally,
      recommendations for future research on the relationship between internalizing
      disorders and SUDs in youth are discussed.

PMID- 20817372
TI  - [History of pubic symphysis separation and mode of delivery].
AB  - Pubic symphysis separation is an underestimated and badly treated pathology. It
      can be responsible for an important morbidity and therefore requires a fast and
      specialized management. In case of subsequent pregnancy, mode of delivery will
      have to be discussed due to traumatic past and maternal fear of recurrence. After
      two cases of patients who experienced preventive cesarean delivery after
      symphyseal separation in a prior pregnancy, a retrospective study reporting pubic
      disjunction cases during the last 10 years in our unit was made. Few data are
      available in the literature and risks of recurrence are not well-defined. Vaginal
      delivery may be proposed, leaving a wide place to discussion with the patient,
      evoking prevention and therapeutic possibilities.

PMID- 20817373
TI  - [Merkel cell carcinoma revisited: a new example of viro-induced human tumour].
AB  - Merkel cell carcinoma (MCC) is a neuroendocrine carcinoma of the skin of poor
      outcome. A new type of virus, isolated in 2008, was found to be strongly
      associated with CCM. This virus, belonging to the family of polyomavirus, was
      called MCPyV for Merkel Carcinoma Polyomavirus. Recent data favour a causative
      role of MCPyV in oncogenesis. MCC represents thus a new model for the
      understanding of the mechanisms of oncogenesis. The distinct molecular viral
      signature in every case of MCC represents an original tool for the follow-up of
      the disease. New therapeutic perspectives are to be drawn using this model.

PMID- 20817374
TI  - [Management of a scabies epidemic in the Strasbourg teaching hospital, France].
AB  - CONTEXT: An outbreak of scabies occurred in the geriatric department of the
      Strasbourg University Hospital in September 2005. The index case presented with
      hyperkeratosic scabies, an extremely contagious form. The epidemic spread to
      several wards and pavilions and also contaminated healthcare staff and patient's
      families. OBJECTIVE: Our objective was to describe the outbreak, its progression,
      and the measures taken to eradicate it. METHODOLOGY: All healthcare workers,
      patients, and families affected in the outbreak were retrospectively studied,
      using medical prescriptions recorded by the hospital pharmacy, listings
      established by the occupational health department, and patient files. RESULTS:
      Two epidemic waves were recorded, between August 31 and December 16, 2005,
      affecting 51 patients and staff members in the geriatric department, with a total
      of 58 episodes of scabies, seven of which were recurrences. Three main measures
      were taken to eradicate the epidemic: setting up of "contact" isolation
      precautions, information for the affected individuals, and treatment of the
      infected patients associated to mass treatment of contact cases. The mass
      treatment was widely applied, involving 490 patients and 592 caregivers. All of
      these measures successfully curtailed the outbreak in 3 months. CONCLUSION: Rapid
      and radical action is essential to prevent extension of scabies within a
      community.

PMID- 20817375
TI  - Sex differences in cardiac injury after severe haemorrhage and ventricular
      fibrillation in pigs.
AB  - AIM OF THE STUDY: Experimental studies have shown sex differences in haemodynamic
      response and outcome after trauma and haemorrhagic shock. We recently reported
      that female sex protects against cerebral injury after exsanguination cardiac
      arrest (CA), independent of sexual effects of hormones. The current study
      examines if female sex is also cardioprotective. METHODS: In this study 21
      sexually immature piglets (12 males and 9 females) were subjected to 5 min of
      haemorrhagic shock followed by 2 min of ventricular fibrillation and 8 min of
      cardiopulmonary resuscitation (CPR). Volume resuscitation was started during CPR
      with intravenous administration of 3 ml kg(-1) hypertonic saline-dextran (HSD)
      solution for 20 min. Sexually immature animals were used to differentiate innate
      sex differences from the effects of sexual hormones. Sex differences in
      haemodynamics, myocardial injury (troponin I), and short-term survival (3-h) were
      evaluated. RESULTS: After resuscitation female animals had a higher blood
      pressure, lower heart rate, lower troponin I concentrations, and higher survival
      rate (100% and 63% in 3 h) despite comparable sex hormone levels. CONCLUSIONS:
      After resuscitation from haemorrhage and circulatory arrest, haemodynamic
      parameters are better preserved and myocardial injury is smaller in female
      piglets. This difference in outcome is independent of sexual hormones.

PMID- 20817377
TI  - Reducing the duration of 100% oxygen ventilation in the early reperfusion period
      after cardiopulmonary resuscitation decreases striatal brain damage.
AB  - PURPOSE: Previous data indicate that 100% O(2) ventilation during early
      reperfusion after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR)
      increases neuronal death. However, current guidelines encourage the use of 100%
      O(2) during resuscitation and for an undefined period thereafter. We
      retrospectively analyzed data from a porcine CA model and hypothesized that
      prolonged hyperoxic reperfusion would be associated with increased
      neurohistopathological damage and impaired neurological recovery. METHODS:
      Fifteen male pigs underwent 8 min of CA and 5 min of CPR. After resuscitation
      animals were ventilated with either 100% oxygen for 60 min (hyperoxia; n=8) or 10
      min (normoxia; n=7). Physiological variables were obtained at baseline and 10, 60
      and 240 min after resuscitation. Daily functional performance was assessed using
      an established neurocognitive test in parallel to a neurological deficit score
      (NDS). On day 5, brains of the re-anaesthetized pigs were harvested for
      neurohistopathological analyses. RESULTS: At baseline there were no differences
      in hemodynamics and neurological status between groups. Post-arrest only PaO(2),
      as a result of the different inspired oxygen fractions, was significantly higher
      in the hyperoxia group. There was a numerical trend towards improved clinical
      recovery in both the NDS and the neurocognitive testing for animals exposed to 10
      min of 100% oxygen. However, hyperoxic animals showed a significantly greater
      degree of necrotic neurons and perivascular inflammation in the striatum in
      comparison to normoxic animals. CONCLUSION: In this retrospective analysis
      prolonged hyperoxia after CA aggravated necrotic brain damage and perivascular
      inflammation in the striatum of pigs.

PMID- 20817376
TI  - Therapeutic hypothermia is associated with a decrease in urine output in acute
      stroke patients.
AB  - AIMS: It is unclear what effect therapeutic hypothermia may have on renal
      function, because its effect has so far been primarily evaluated in settings in
      which there may be possible confounding perturbations in cardiovascular and renal
      physiology, such deep intraoperative hypothermia, general anesthesia, and post
      cardiac arrest. We sought to determine if therapeutic hypothermia affects renal
      function in awake patients with normal renal function who were enrolled into a
      clinical trial of hypothermia plus intravenous thrombolysis for acute ischemic
      stroke. METHODS: Eleven patients with normal renal function were cooled to 33
      degrees C for 24 h using an endovascular catheter, and then re-warmed over 12 h
      to 36.5 degrees C, while hourly temperature, blood pressure, and fluid status
      data was recorded. Blood samples for blood urea nitrogen (BUN), creatinine, and
      hematocrit were drawn prior to treatment (baseline), immediately after
      hypothermia and re-warming (day 2), and again at day 7 or discharge, and values
      compared. RESULTS: On initiation of cooling, temperatures dropped from a median
      pre-treatment value of 36.1 degrees C (IQR: 35.8-36.4 degrees C) to 33.1 degrees
      C (IQR: 33.1-33.4 degrees C). Urine output decreased 5.1 ml/h for every 1 degrees
      C decrease in body temperature (p-value=0.001), with no associated serious
      adverse events. There were no statistically significant changes in BUN,
      creatinine, or hematocrit in the hypothermia patients. CONCLUSION: Inducing
      hypothermia in patients with relatively unperturbed renal physiology results in a
      decrease in urine output that is linearly correlated with the decrease in core
      temperature. This has important implications for fluid management in patients
      undergoing therapeutic hypothermia.

PMID- 20817378
TI  - Statistical inference: hypothesis testing.
AB  - The aim of statistical inference is to predict the parameters of a population,
      based on a sample of data. Inferential statistics encompasses the estimation of
      parameters and model predictions. The present article describes the hypothesis
      tests or statistical significance tests most commonly used in healthcare
      research.

PMID- 20817379
TI  - Reproducibility of the gadolinium concentration measurements and of the fitting
      parameters of the vascular input function in the superior sagittal sinus in a
      patient population.
AB  - It is widely recognised that the measurement of the arterial input function (AIF)
      is a key issue and a major source of errors in the pharmacokinetic modelling of
      dynamic, contrast-enhanced magnetic resonance imaging (DCE-MRI) data, and the
      modality of the AIF determination is still a matter of debate. In this study we
      addressed the problem of the intrinsic variability of the AIF within the imaged
      volume of a DCE-MRI scan by systematically investigating the change in the
      concentration of contrast agent over time and the fit parameters of the derived
      vascular input function (VIF) obtained from the superior sagittal sinus (SSS) of
      a patient population that was scanned longitudinally during treatment for high
      grade glioma. From a total of 82 scanning sessions, we compared the results
      obtained with three different DCE-MRI protocols and between two different fitting
      functions. We applied a correction algorithm to the measured concentration-time
      curves to minimize the effect of the low temporal resolution on the VIF, and
      investigated the effect of this algorithm on the reproducibility. Finally, where
      possible, we compared the signal obtained in the SSS to the signal obtained in
      the middle cerebral artery. We found a good intrapatient reproducibility of both
      the measured gadolinium concentrations and VIF parameters, and that the variation
      of the parameters due to slice location within a patient was significantly lower
      than the intra patient variation. Intrapatient, interscan differences were
      significantly less marked than inter-patient differences showing a good
      intraclass correlation coefficient. We did encounter a MRI protocol dependence of
      the VIF fitting parameters. The correction algorithm significantly improved the
      reproducibility of the fitting parameters. These results support the idea that
      the use of a patient specific measured AIF, not necessarily averaged over a large
      volume, offers a significant benefit with respect to an external AIF or a
      measured cohort average AIF.

PMID- 20817380
TI  - Surgical repair of blunt force penetrating anogenital trauma in an 18-month-old
      sexually abused girl: a case report.

PMID- 20817381
TI  - Informal discussions in substance abuse treatment sessions with Spanish-speaking
      clients.
AB  - This study investigated the extent to which bilingual counselors initiated
      informal discussions about topics that were unrelated to the treatment of their
      monolingual Spanish-speaking Hispanic clients in a National Institute on Drug
      Abuse Clinical Trial Network protocol examining the effectiveness of motivational
      enhancement therapy (MET). Session audiotapes were independently rated to assess
      counselor treatment fidelity and the incidence of informal discussions. Eighty
      three percent of the 23 counselors participating in the trial initiated informal
      discussions at least once in one or more of their sessions. Counselors delivering
      MET in the trial initiated informal discussion significantly less often than the
      counselors delivering standard treatment. Counselors delivering standard
      treatment were likely to talk informally the most when they were ethnically non
      Latin. In addition, informal discussion was found to have significant inverse
      correlations with client motivation to reduce substance use and client retention
      in treatment. These results suggest that informal discussion may have adverse
      consequences on Hispanic clients' motivation for change and substance abuse
      treatment outcomes and that maintaining a more formal relationship in early
      treatment sessions may work best with Hispanic clients. Careful counselor
      training and supervision in MET may suppress the tendency of counselors to talk
      informally in sessions.

PMID- 20817382
TI  - Motivational interviewing with significant other participation: assessing
      therapeutic alliance and patient satisfaction and engagement.
AB  - Inclusion of concerned significant others (SOs) in alcohol use treatment has
      demonstrated efficacy but has not been tested in the context of brief
      interventions. In this study, individual motivational interviewing (MI) sessions
      were compared with MI sessions including a significant other on within-treatment
      outcomes (alliance, fidelity, client satisfaction, and engagement). Participants
      (N = 382) were adult alcohol users recruited in a Level I trauma center.
      Perceived alliance did not differ across conditions, but patients and SOs
      reported higher alliance, satisfaction, and engagement than was perceived by the
      therapist. The occurrence of MI components, or discussion areas, was consistent
      across conditions. Higher baseline SO drinking was associated with lower patient
      engagement, whereas higher baseline SO acceptance of patient drinking was
      associated with lower SO engagement. Results suggest that individual MI sessions
      can be adapted to include an SO with minimal impact on patient acceptability and
      treatment fidelity. Research should, however, consider SOs' influence on
      participant outcomes and the relevance of specific SO characteristics.

PMID- 20817384
TI  - The SUMMIT trial: a field comparison of buprenorphine versus methadone
      maintenance treatment.
AB  - This prospective patient-preference study examined the effectiveness in practice
      of methadone versus buprenorphine maintenance treatment and the beliefs of
      subjects regarding these drugs. A total of 361 opiate-dependent individuals (89%
      of those eligible, presenting for treatment over 2 years at a drug service in
      England) received rapid titration then flexible dosing with methadone or
      buprenorphine; 227 patients chose methadone (63%) and 134 buprenorphine (37%).
      Participants choosing methadone had more severe substance abuse and psychiatric
      and physical problems but were more likely to remain in treatment. Survival
      analysis indicated those prescribed methadone were over twice as likely to be
      retained (hazard ratio for retention was 2.08 and 95% confidence interval [CI] =
      1.49-2.94 for methadone vs. buprenorphine), However, those retained on
      buprenorphine were more likely to suppress illicit opiate use (odds ratio =
      2.136, 95% CI = 1.509-3.027, p < .001) and achieve detoxification. Buprenorphine
      may also recruit more individuals to treatment because 28% of those choosing
      buprenorphine (10% of the total sample) stated they would not have accessed
      treatment with methadone.

PMID- 20817383
TI  - Substance use patterns among first-year college students: secondary effects of a
      combined alcohol intervention.
AB  - This study explored secondary effects of a multisite randomized alcohol
      prevention trial on tobacco, marijuana, and other illicit drug use among a sample
      of incoming college students who participated in high school athletics. Students
      (n = 1,275) completed a series of Web-administered measures at baseline during
      the summer before starting college and 10 months later. Students were randomized
      to one of four conditions: a parent-delivered intervention, a brief motivation
      enhancement intervention (Brief Alcohol Screening and Intervention for College
      Students [BASICS]), a condition combining the parent intervention and BASICS, and
      assessment-only control. A series of analyses of variance evaluating drug use
      outcomes at the 10-month follow-up assessment revealed significant reductions in
      marijuana use among students who received the combined intervention compared to
      the BASICS-only and control groups. No other significant differences between
      treatment conditions were found for tobacco or other illicit drug use. Our
      findings suggest the potential utility of targeting both alcohol and marijuana
      use when developing peer- and parent-based interventions for students
      transitioning to college. Clinical implications and future research directions
      are considered.

PMID- 20817385
TI  - Hereditary renal cancer syndromes: an update of a systematic review.
AB  - CONTEXT: Hereditary renal cancers (HRCs) comprise approximately 3-5% of renal
      cell carcinomas (RCCs). OBJECTIVE: Our aim was to provide an overview of the
      currently known HRC syndromes in adults. EVIDENCE ACQUISITION: Data on HRC
      syndromes were analysed using PubMed and Online Mendelian Inheritance in Man with
      an emphasis on kidney cancer, clinical criteria, management, treatment, and
      genetic counselling and screening. EVIDENCE SYNTHESIS: Ten HRC syndromes have
      been described that are inherited with an autosomal dominant trait. Eight genes
      have already been identified (VHL, MET, FH, FLCN, TSC1, TSC2, CDC73, and SDHB).
      These HRC syndromes involve one or more RCC histologic subtypes and are generally
      bilateral and multiple. Computed tomography and magnetic resonance imaging are
      the best imaging techniques for surveillance and assessment of renal lesions, but
      there are no established guidelines for follow-up after imaging. Except for
      hereditary leiomyomatosis RCC tumours, conservative treatments favour both an
      oncologically effective therapeutic procedure and a better preservation of renal
      function. CONCLUSIONS: HRC involves multiple clinical manifestations, histologic
      subtypes, genetic alterations, and molecular pathways. Urologists should know
      about HRC syndromes in the interest of their patients and families.

PMID- 20817386
TI  - [Proceedings of the 24th meeting of the Anesthesiology-Reanimation Club in ORL
      (Carorl)].

PMID- 20817387
TI  - [Pemphigus].
AB  - Pemphigus is a rare autoimmune blistering disorder involving the skin and
      mucosae. Three types of pemphigus have been described, including pemphigus
      vulgaris, pemphigus foliaceus and paraneoplastic pemphigus. Diagnosis of the type
      of pemphigus is made by the combination of clinical features, histological and
      direct immunofluorescence findings, and serum analysis by indirect
      immunofluorescence, immunoblot analysis and enzyme-linked-immunosorbent-assay
      (Elisa). Most patients are treated with oral corticosteroids, sometimes
      associated with immunosuppressants. Patients with treatment failure or with
      contraindications to systemic corticosteroids and/or immunosuppressants may be
      treated with intravenous immunoglobulins or rituximab, an anti-CD20 monoclonal
      antibody.

PMID- 20817388
TI  - Correlation of clinical findings and results of percutaneous balloon compression
      for patients with trigeminal neuralgia.
AB  - OBJECTIVE: To investigate pain relief and recurrence after percutaneous balloon
      compression (PBC) and its association with type of pain, prior surgery, or other
      clinical factors. METHODS: Fifty-nine patients with medically refractory
      trigeminal pain were enrolled into this study. Patients were divided into those
      with typical trigeminal neuralgia (TN), and those with other types of trigeminal
      pain or "atypical pain." The post-surgical rate of recurrence was estimated by
      the Kaplan-Meier method. Cox-proportional hazards models were used to investigate
      associations between patient characteristics and recurrence of pain. RESULTS:
      Forty-two patients had TN, 17 patients had atypical pain. At last follow-up, 40
      patients had excellent, 9 good, 7 fair and 3 poor pain relief. Recurrence was
      observed in 35 patients, and was associated with pain type (relative risk
      (RR)=2.38, 95% confidence interval (CI): 1.22-4.63, P=0.011) and pain duration
      before PBC (RR=1.33, 95% CI: 1.02-1.72, P=0.033). Other clinical factors were not
      significant. Two patients had transient paresis of the sixth cranial nerve,
      however, there were no permanent post-surgical complications. CONCLUSIONS: Our
      study demonstrates the safety and efficacy of PBC with 83% of patients being pain
      free at last follow-up. Patients with atypical pain and longer pre-surgical
      symptom duration appear to have a higher risk of recurrence. Repeat surgery is
      just as effective as initial surgery, justification for being conservative in
      parameter selection at the initial procedure to minimize complications.

PMID- 20817389
TI  - Limitations of imageless computer-assisted navigation for total hip arthroplasty.
AB  - We prospectively evaluated acetabular cup placement in total hip arthroplasty
      with an imageless computer navigation system or using conventional manual
      technique. The achieved cup orientation in the manual group had substantially
      larger variances and greater placement error than the navigation cases. The use
      of navigation was abandoned in 3 cases because of excessive pelvic tilt and
      unreliable registration of the pelvis. Computer navigation system helped improve
      the accuracy of the acetabular cup placement for total hip arthroplasty in this
      study. The variation between the intraoperative navigation readings and the
      computed tomographic values suggests that relying on palpation of bony landmarks
      through drapes and tissue is a limitation of this method. Further, the variation
      in pelvic tilt has an effect on cup placement that requires further studies.

PMID- 20817390
TI  - Does the Oxford Knee Score complement, concur, or contradict the American Knee
      Society Score?
AB  - The American Knee Society Score (AKSS) and the Oxford Knee Score (OKS) are
      commonly used outcome assessment tools following total knee arthroplasty. The
      literature is sparse with regard to direct correlation between the AKSS and the
      OKS. The present study aimed to elucidate any direct correlation between these
      two scoring systems. Preoperative and 1-year postoperative AKSS and OKS from 379
      patients were analyzed statistically. Regression equations were developed based
      on curve fit models. The study found a good correlation between the two scoring
      systems. The OKS can be used as a screening tool to identify which patients need
      to be assessed clinically in the short term (<2 years) following total knee
      arthroplasty (TKA). This will have significant cost-benefit implications. It is
      also possible to predict the AKSS from OKS using mathematical equations developed
      for this study. This method of predicting the AKSS from the OKS has not
      previously been described.

PMID- 20817391
TI  - Locking compression plates for the treatment of periprosthetic femoral fractures
      around well-fixed total hip and knee implants.
AB  - There are currently few published studies examining the use of locking
      compression plates for the treatment of periprosthetic femoral fractures. Fifteen
      total hip or knee arthroplasty patients with 16 Vancouver type B1 and C fractures
      with an average age of 76 years were fixed and followed clinically and
      radiographically for 2 years. Fourteen patients achieved radiographic union by 6
      months, and 13 patients were ambulatory by 6 months. There were no intraoperative
      complications. In summary, locking plates offer a viable treatment option for
      these difficult fractures. We advocate a minimum of 10 cortices of fixation (with
      unicortical or bicortical screws and cable combinations) above and below the
      fracture. Bone grafting should be used if the soft tissue envelope is violated
      with extensive dissection, and cortical struts should be considered in cases of
      failed hardware and revision fixation.

PMID- 20817392
TI  - Knee arthrotomy repair with a continuous barbed suture: a biomechanical study.
AB  - We compared knee arthrotomy closures using interrupted biodegradable sutures and
      running bidirectionally barbed sutures in cadaveric specimens subjected to cyclic
      loading. During the initial 2000 flexion cycles, both groups maintained closure
      and no suture ruptured. Suture throws were then sequentially cut to weaken the
      repairs, and the knees were cyclically flexed after each cut. Both types of
      suture repairs survived the cutting of the first throw or stitch and subsequent
      cyclical testing. However, there was a significant difference in the repairs
      after multiple cuts (log-rank test, P < .003). None of the knees in the
      interrupted suture group survived more than 3 cuts, whereas in the barbed repair
      group, it took the severing of as many as 7 throws for failure to occur.

PMID- 20817394
TI  - Mechanism of thermal decomposition of a pesticide for safety concerns: case of
      Mancozeb.
AB  - Thermal decomposition under both air and inert atmospheres of a commercial
      Mancozeb product was investigated through thermogravimetric analysis and
      laboratory scale thermal treatment from 20 degrees C to 950 degrees C, with
      analysis of gaseous and solid products. The aim of this study is the
      understanding of the thermal degradation mechanisms of a pesticide under
      different atmospheres and the chemical identification of the solid and gaseous
      pollutants which can be emitted during warehouse fires and which can constitute a
      threat for health and environment. Pyrolysis of Mancozeb takes place between 20
      degrees C and 950 degrees C and lead essentially to CS(2) and H(2)S emissions
      with formation at 950 degrees C of MnS and ZnS. Thermal oxidation of Mancozeb
      under air occurs between 150 degrees C and 950 degrees C with formation of CO,
      CO(2) and sulphur gases (CS(2) and SO(2)). The first step (155-226 degrees C) is
      the loss of CS(2) and the formation of ethylene thiourea, ZnS and MnS. The
      metallic sulphides are oxidized in ZnO and MnSO(4) between 226 degrees C and 650
      degrees C (steps 2 and 3). MnSO(4) is then oxidized in Mn(3)O(4) during the last
      step (step 4) between 650 degrees C and 950 degrees C. At 950 degrees C, carbon
      recovery is close to 95%. Sulphur recovery is close to 98% with an equal
      partition between SO(2) and CS(2).

PMID- 20817393
TI  - Caspase-8 as a therapeutic target in cancer.
AB  - Caspase-8 is an apical caspase which initiates programmed cell death following
      death receptor ligation. This central role in apoptosis has prompted significant
      clinical interest in regulating caspase-8 expression and proteolytic activity.
      However, caspase-8 has also been found to play a number of non-apoptotic roles in
      cells, such as promoting activation NF-kappaB signaling, regulating autophagy and
      altering endosomal trafficking, and enhancing cellular adhesion and migration.
      Therefore, depending upon the specific cellular context, caspase-8 may either
      potentiate or suppress tumor malignancy. Accordingly, a marked heterogeneity
      exists in the expression patterns of caspase-8 among different tumor types.
      Therapeutics have been developed which can increase caspase-8 expression, yet it
      remains unclear whether this approach will be beneficial in all cases. Care is
      warranted, and the role of caspase-8 should be addressed on a case by case basis.

PMID- 20817395
TI  - Preparation, characterization and photocatalytic activity of a novel composite
      photocatalyst: ceria-coated activated carbon.
AB  - In the present work, a novel composite photocatalyst ceria-coated activated
      carbon (CCAC) was prepared by a facile method. The composite photocatalyst was
      characterized by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), scanning
      electron microscopy (SEM) and photocatalytic degradation of 4-chlorophenol (4
      CP). A synergy effect for 4-CP degradation was observed because the activated
      carbon (AC) with strong adsorbent activity provided sites for the adsorption of 4
      CP. Then, the adsorbed 4-CP can migrate continuously onto the surface of ceria
      particles and then degraded at there. Hydroquinone (HQ) and benzoquinone (BQ)
      were found to be the main intermediates of the photocatalytic 4-CP degradation
      with ceria or CCAC by HPLC measurement. The results suggested that the same
      reaction mechanism occurred in the presence of ceria or titania.

PMID- 20817396
TI  - Structural effects of the bioavailable fraction of pesticides in soil:
      suitability of elutriate testing.
AB  - This study focused the ecotoxicological evaluation of four different pesticides
      (chlorpyrifos, glyphosate, vinclozolin, endosulfan), sprayed into an agricultural
      soil, using a standard battery of aquatic bioassays for testing of soil
      elutriates: Vibrio fischeri -Microtox((r)); Pseudokirchneriella subcapitata
      growth inhibition; Daphnia magna acute and chronic toxicity. Despite relevant
      pesticide residues were recovered from the soil matrix (concentrations higher
      than 1000 MUg kg(-1)), much lower concentrations could be retrieved from
      elutriates (highest records for endosulfan of ca. 250 ng L(-1)and 1400 ng L(-1);
      dissolved and particulate concentration, respectively) and little effects were
      generally found in the bioassays. Lethal effects (D. magna 48 h-EC50 of 36.8%)
      could be noticed following exposure to the endosulfan elutriate. Elutriates
      induced no toxicity on V. fischeri; algal growth was generally inhibited at high
      elutriate dilutions and stimulated at the lower elutriate dilutions; and no
      overall impairment of D. magna life-history was noticed. Results revealed that
      cross-contamination during field application, input of organic matter and
      nutrients by elutriates in test solutions, and choice of test species and
      endpoints may constrain the ecotoxicological assessment. Suitability of
      established aquatic bioassay test batteries for these purposes, and questioning
      on whether direct assays with soil organisms could be more protective tools is
      discussed.

PMID- 20817397
TI  - Comparative proteomic analysis of Typha angustifolia leaf under chromium, cadmium
      and lead stress.
AB  - The present study investigated Typha angustifolia leaf proteome in response to
      Cr, Cd and Pb stress. T. angustifolia of 90 (D90) and 130d (D130) old plants were
      subjected to 1mM Cr, Cd and Pb and samples were collected 30d after treatment. 2
      DE coupled with MS (mass spectrometry) was used to analyze and identify Cr, Cd
      and Pb-responsive proteins. More than 1600 protein spots were reproducibly
      detected on each gel, wherein 44, 46, 66 and 33, 26, 62 spots in D90 and D130
      samples were differentially expressed by Cr, Cd, Pb over the control,
      respectively. Of these differentially expressed proteins, 3, 1, 8 overlapped in
      D90 and D130; while 5, 8, 5 with regulation factors above 3 in one of D90 or D130
      samples. Total of 22 and 4 up- and down-regulated proteins were identified using
      MS and data bank analysis. Cr-induced expression of ATP synthase, RuBisCO small
      subunit and coproporphyrinogen III oxidase; Cd-induced RuBisCO large subunit; Pb
      up-regulated carbohydrate metabolic pathway enzymes of fructokinase, and improved
      RuBisCO activase and large subunit, Mg-protoporphyrin IX chelatase. Contrarily,
      elF4F was inhibited by Cr/Pb, chloroplast FtsZ-like protein and GF14 omega
      impeded by Cd and Pb, respectively.

PMID- 20817398
TI  - Phosphate mine wastes reuse for phosphorus removal from aqueous solutions under
      dynamic conditions.
AB  - Phosphate mine slimes (PMS), an abundant waste generated from phosphate mines,
      was used in this study as a cost-effective adsorbent to investigate the phosphate
      anions removal from synthetic and urban secondary treated wastewater solutions.
      Dynamic experiments using laboratory reactors were carried out to study the
      effect of phosphate influent concentration, PMS dosage and feed flow rate on
      phosphate removal and a kinetic model was used to determine the phosphate mass
      transfer coefficients. The results show that the phosphate removal increases with
      influent phosphate concentration and PMS dosage. The feed flow rate has no
      significant effect. On the other hand, the phosphate removal from wastewater is
      less efficient than the synthetic solution due to anions competition process. The
      evaluation of phosphates mass transfer coefficients confirms the presence of
      anion competition phenomena and the necessity of increasing PMS dosage to provide
      more adsorption sites. The cost-effective and high adsorptive capability of PMS
      make them attractive materials for phosphate anions removal and recovery from
      secondary treated wastewaters with the possibility of agronomic reuse as
      fertilizer.

PMID- 20817399
TI  - Industrial accidents triggered by lightning.
AB  - Natural disasters can cause major accidents in chemical facilities where they can
      lead to the release of hazardous materials which in turn can result in fires,
      explosions or toxic dispersion. Lightning strikes are the most frequent cause of
      major accidents triggered by natural events. In order to contribute towards the
      development of a quantitative approach for assessing lightning risk at industrial
      facilities, lightning-triggered accident case histories were retrieved from the
      major industrial accident databases and analysed to extract information on types
      of vulnerable equipment, failure dynamics and damage states, as well as on the
      final consequences of the event. The most vulnerable category of equipment is
      storage tanks. Lightning damage is incurred by immediate ignition, electrical and
      electronic systems failure or structural damage with subsequent release. Toxic
      releases and tank fires tend to be the most common scenarios associated with
      lightning strikes. Oil, diesel and gasoline are the substances most frequently
      released during lightning-triggered Natech accidents.

PMID- 20817400
TI  - Fenton degradation of tetrachloroethene and hexachloroethane in Fe(II) catalyzed
      systems.
AB  - The degradation of tetrachlorothene (PCE) and hexachloroethane (HCA) using Fe(II)
      and Fe(II)-citrate at different H(2)O(2) concentrations was studied to clarify
      the role of oxidation and reduction pathways in Fenton chemistry. The
      interactions between oxidative and reductive radicals, and the cyclic nature of
      the Fe(II)-Fe(III) ions make for a complex system that displays a suppression or
      enhancement of PCE or HCA degradation as the experimental conditions are varied.
      PCE degradation decreased, while HCA degradation increased, for larger H(2)O(2)
      concentration. The degradations of PCE and HCA were lower in vials where they
      were individually present compared to vials with the PCE-HCA mixture. Using
      Fe(II)-citrate instead of Fe(II) resulted in slower PCE and insignificant HCA
      degradation. These observations indicate that degradation efficiency losses arise
      from interactions between the oxidant and reductant radical moieties, and that
      the production of reduction radicals is only significant when the hydroxyl
      radical (OH) production is rapid.

PMID- 20817402
TI  - Fentanyl for breakthrough cancer pain--what's new?

PMID- 20817403
TI  - A fast method to approximately train hard support vector regression.
AB  - The hard support vector regression (HSVR) usually has a risk of suffering from
      overfitting due to the presence of noise. The main reason is that it does not
      utilize the regularization technique to set an upper bound on the Lagrange
      multipliers so they can be magnified infinitely. Hence, we propose a greedy
      stagewise based algorithm to approximately train HSVR. At each iteration, the
      sample which has the maximal predicted discrepancy is selected and its weight is
      updated only once so as to avoid being excessively magnified. Actually, this
      early stopping rule can implicitly control the capacity of the regression
      machine, which is equivalent to a regularization technique. In addition, compared
      with the well-known software LIBSVM2.82, our algorithm to a certain extent has
      advantages in both the training time and the number of support vectors. Finally,
      experimental results on the synthetic and real-world benchmark data sets also
      corroborate the efficacy of the proposed algorithm.

PMID- 20817401
TI  - The relationship of demographic and psychosocial variables to pain-related
      outcomes in a rural chronic pain population.
AB  - Rural residency and low socioeconomic status (SES) are associated with increased
      likelihood of chronic pain. Other demographics are also differentially associated
      with the experience of pain. This study examines the relations between
      demographic and pain-related variables in a virtually unstudied population of
      rural Alabama chronic pain patients. One hundred and fifteen patients completed
      validated measures of pain catastrophizing, depression, pain intensity, pain
      interference, perceived disability, and life satisfaction. Average age of study
      participants was 52-years, 79% were female, 74% were African-American, 72%
      reported annual income between 00,000-12,999, and 61% were unemployed. Although
      average years of reported education was 12.26, reading level percentile (primary
      literacy indicant) was 17.33. Cross-sectional multivariate and univariate
      analyses were conducted to examine associations among demographic and
      psychosocial variables in relation to various pre-treatment pain-related
      variables. The mediating role of pain catastrophizing and depression was
      investigated. Results indicate that race was significantly associated with pain
      intensity and pain interference, such that African-Americans reported higher
      scores than White-Americans. Pain catastrophizing was uniquely associated with
      pain intensity, pain interference, and perceived disability; depression was
      uniquely associated with pain interference and life satisfaction. Pain
      catastrophizing mediated the relation between primary literacy and pain
      intensity; age effects were differentially mediated by either pain
      catastrophizing or depression. These analyses provide an insight into the
      specific demographic and psychosocial factors associated with chronic pain in a
      low-literacy, low-SES rural population.

PMID- 20817404
TI  - Genetic analysis and development of species-specific PCR assays based on ITS-1
      region of rRNA in bovine Eimeria parasites.
AB  - At present, morphological characteristics of oocyst is the only achievable method
      for the identification of bovine coccidia to the species level. In this study,
      the internal transcribed spacer 1 (ITS-1) region of ribosomal RNA genes of six
      bovine Eimeria species; E. alabamensis, E. auburnensis, E. bovis, E. cylindrica,
      E. ellipsoidalis and E. zuernii, were sequenced and analyzed the phylogenetic
      relationship among them. In pair-wise alignment, the sequences among the same
      species had high homology of over 90%. E. bovis and E. zuernii were closely
      related within the same cluster. This cluster and E. alabamensis were distant
      from major cluster of bovine coccidia that included E. auburnensis, E. cylindrica
      and E. ellipsoidalis. Species-specific PCR assays based on the amplification of
      the ITS-1 region were also developed to identify the 6 pathogens. The ITS-1
      region of each Eimeria species had sufficient inter-specific sequence variation
      enough to design the primer sets that differentially amplified each target
      species. This PCR assay for the detection and differentiation of Eimeria parasite
      showed higher sensitivity when compared to the conventional oocyst-morphological
      examination. This is the first attempt for the identification of 6 bovine Eimeria
      parasites in the genomic level and may provide as useful methods for diagnosis
      and epidemiology of bovine coccidial infection.

PMID- 20817405
TI  - The odd couple: a fresh look at autoimmunity and immunodeficiency.
AB  - The paradoxical relationship between immunodeficiency (under-responsiveness) and
      autoimmunity (over-responsiveness) affecting the immune system was debated at the
      Fourth AARDA Colloquium on cross-disciplinary issues in autoimmunity.
      Immunodeficiency disease and autoimmune disease, far from being mutually
      exclusive, share profound dysregulation of the immune system. Among the most
      keenly discussed issues were: i) the remarkably high number of molecularly
      identified primary immunodeficiencies with autoimmune expressions; ii) the
      homeostasis of immune function such that deficiency in any one given compartment
      can result in over activity in the same or another compartment; iii) whilst some
      immune deficiency states are essentially monogenic, each of them can exhibit
      striking variability in autoimmune outcome, indicative of epigenetic or
      environmental influences on phenotypic expression; iv) innate immunity,
      particularly complement defects, as well as adaptive immunity, is complicit in
      the immunodeficiency-autoimmunity axis; v) features of certain of the disorders
      discussed at the meeting forced a reappraisal of what actually is meant by
      'autoimmune disease'. It was concluded that genes that determine inherited
      immunodeficiencies, hitherto rather neglected by autoimmunologists, compel
      attention to consideration of molecular genetic anomalies critical for emergence
      of autoimmune disease in humans and animals.

PMID- 20817406
TI  - Sunitinib for the treatment of metastatic renal cell carcinoma.
AB  - Sunitinib is an orally administered multitargeted tyrosine kinase inhibitor
      approved multinationally for the first- and second-line treatment of metastatic
      renal cell carcinoma (mRCC). The recommended dose of sunitinib is 50mg per day
      for 4 weeks followed by 2 weeks off-treatment (Schedule 4/2). In a phase III
      trial in 750 patients with mRCC who had not received prior treatment, sunitinib
      demonstrated superior efficacy to interferon-alpha for the first-line treatment
      of mRCC. Sunitinib doubled progression-free survival compared with interferon
      alpha; furthermore, median OS with sunitinib was greater than 2 years. As a
      result, sunitinib is now considered a reference standard of care for first-line
      mRCC treatment in patients at favourable or intermediate prognostic risk and is
      recommended in treatment guidelines. Additionally, results from an expanded
      access programme, in a broad, heterogeneous patient population, confirmed the
      efficacy of sunitinib. Sunitinib has a distinct and predictable profile of
      adverse events, most of which are manageable with standard medical interventions.
      Therapy management strategies, including optimisation of dose and treatment
      duration and adverse event management can help patients achieve optimal efficacy
      with sunitinib in clinical practice. To further improve outcomes in patients with
      mRCC, current trials are evaluating sequencing or combination of targeted agents.
      The use of sunitinib as adjuvant therapy after nephrectomy and as neoadjuvant
      therapy is also being assessed. This paper provides an in-depth critical review
      of sunitinib, with particular focus on the data supporting the use of sunitinib
      for mRCC.

PMID- 20817407
TI  - Systematic review and meta-analysis of radiotherapy in various head and neck
      cancers: comparing photons, carbon-ions and protons.
AB  - PURPOSE: To synthesize and compare available evidence considering the
      effectiveness of carbon-ion, proton and photon radiotherapy for head and neck
      cancer. METHODS: A systematic review and meta-analyses were performed to retrieve
      evidence on tumor control, survival and late treatment toxicity for carbon-ion,
      proton and the best available photon radiotherapy. RESULTS: In total 86
      observational studies (74 photon, 5 carbon-ion and 7 proton) and eight
      comparative in-silico studies were included. For mucosal malignant melanomas, 5
      year survival was significantly higher after carbon-ion therapy compared to
      conventional photon therapy (44% versus 25%; P-value 0.007). Also, 5-year local
      control after proton therapy was significantly higher for paranasal and sinonasal
      cancer compared to intensity modulated photon therapy (88% versus 66%; P-value
      0.035). No other statistically significant differences were observed. Although
      poorly reported, toxicity tended to be less frequent in carbon-ion and proton
      studies compared to photons. In-silico studies showed a lower dose to the organs
      at risk, independently of the tumor site. CONCLUSIONS: For carbon-ion therapy,
      the increased survival in mucosal malignant melanomas might suggest an advantage
      in treating relatively radio-resistant tumors. Except for paranasal and sinonasal
      cancer, survival and tumor control for proton therapy were generally similar to
      the best available photon radiotherapy. In agreement with included in-silico
      studies, limited available clinical data indicates that toxicity tends to be
      lower for proton compared to photon radiotherapy. Since the overall quantity and
      quality of data regarding carbon-ion and proton therapy is poor, we recommend the
      construction of an international particle therapy register to facilitate
      definitive comparisons.

PMID- 20817408
TI  - Lymph duct ligation during ischemia/reperfusion prevents pulmonary dysfunction in
      a rat model with omega-3 polyunsaturated fatty acid and glutamine.
AB  - OBJECTIVE: The release of injurious factors into the mesenteric lymph from the
      ischemic intestine has been shown to contribute to lung injury and systemic
      inflammation after severe injury. We studied the effects of lung injury and
      systemic inflammatory reaction after intestinal ischemia/reperfusion and
      mesenteric lymph duct ligation with different nutritional statuses. METHODS: Rats
      (n = 72) were fed with a normal diet or received one of three diets (enteral
      nutrition, glutamine, or omega-3 polyunsaturated fatty acid) that were isocaloric
      and isonitrogenous. After 7 d, rats were subjected to 60 min of intestinal
      ischemia, ischemia plus mesenteric lymph duct ligation, or sham procedures. After
      3 d of ischemia, the lymph nodes, lung, intestinal, liver, and blood were
      harvested and analyzed. RESULTS: In the different groups, lung injury, including
      levels of myeloperoxidase, nitric oxide, nitric oxide synthase, and the index of
      alveolar apoptosis, were partly prevented by mesenteric lymph duct ligation (P <
      0.05). Likewise, the rats with ischemia/reperfusion, but not those with duct
      ligation plus ischemia/reperfusion, had a significant increase in intestinal
      permeability and decreased mucosal thickness. The serum cytokine and endotoxin
      concentrations were also lower in the lymph duct ligation groups, although there
      was no significant difference between lymph duct ligation and sham procedure. The
      lung and intestinal injuries were attenuated in the groups fed with glutamine and
      omega-3 polyunsaturated fatty acid. CONCLUSION: These results indicate that lymph
      duct ligation prevents lung injury, a systemic inflammation reaction, and gut
      barrier dysfunction. Enteral glutamine and omega-3 polyunsaturated fatty acid
      modified the gut inflammation, prevented lung injury, and attenuated the systemic
      inflammation reaction.

PMID- 20817409
TI  - Immediate reductions in misperceived social norms among high-risk college student
      groups.
AB  - The current quasi-experimental design evaluated whether a brief, live,
      interactive, normative group (BLING) intervention produced immediate reductions
      in group-specific normative perceptions and whether the magnitude of these
      misperceptions differed among three at risk undergraduate populations: first-year
      students (N=767), Greek-affiliated students (N=555), and student-athletes
      (N=524). In a live group setting, participants used wireless keypads to enter in
      normative perceptions of their group's drinking levels, followed by their own
      actual drinking behaviors. Feedback data illustrating the discrepancies between
      perceived and actual norms were then presented graphically on a large screen.
      Across all groups at pre-intervention, respondents reported significantly higher
      perceived group-specific norms than actual alcohol use, with magnitude of initial
      misperceptions varying by group. The BLING intervention was equally effective in
      immediately correcting normative misperceptions among all three groups regardless
      of gender or the magnitude of initial misperception. These data further validate
      the ability of live normative group-specific data-collection and feedback to
      overcome saliency and credibility issues exhibited by many existing social norms
      interventions.

PMID- 20817410
TI  - Intervention defensiveness as a moderator of drinking outcome among heavy
      drinking mandated college students.
AB  - The efficacy of the Alcohol Skills Training Program (ASTP; Miller, et al., 2000)
      was evaluated in 204 heavy-drinking college students randomly assigned to either
      ASTP (n=119) or an assessment-only control (n=85) condition. The volunteer ASTP
      sample (n=119) was also compared to a sample of students mandated to ASTP
      following a first-time sanction (n=90). At baseline, mandated students reported
      lower levels of peak drinking, negative consequences, readiness to change and
      higher defensiveness than voluntary students. However, the voluntary sample
      showed reductions in problem drinking indicators over time such that there were
      no differences from mandated students at follow-up. There were no outcome
      differences between volunteers assigned to ASTP versus assessment-only. A new
      measure of defensiveness was evaluated and had a significant moderating effect on
      ASTP outcome for peak drinking consumed on a peak occasion at follow-up among
      mandated students.

PMID- 20817411
TI  - Left ventricular untwisting during left atrial contraction: a marker for chronic
      left ventricular diastolic dysfunction?
AB  - BACKGROUND: Left ventricular (LV) untwisting is commonly seen during left atrial
      (LA) contraction. The purpose of this study was to test the hypothesis that this
      characteristic motion is associated with chronic LV diastolic dysfunction.
      METHODS AND RESULTS: Ninety-two patients with cardiovascular risk factors and 36
      age-matched normal individuals were included in the present study, and were
      examined by echocardiography, including conventional, tissue Doppler, and two
      dimensional speckle tracking methods, to clarify the predictors related to late
      diastolic untwisting rate (LDUTR). There was no significant difference in LV
      ejection fraction between patient and control groups. The ratio of peak early
      diastolic transmitral flow velocity to peak early diastolic mitral annular motion
      velocity (E/e') and LA volume index in the patient group were significantly
      greater compared to the ratio of peak early to late diastolic transmitral flow
      velocity (E/A) >=1 group of the controls. The LDUTR in the E/A <1 group of the
      controls was significantly greater compared to the E/A >=1 group of the controls
      and patient group. The LDUTR correlated with end-diastolic LV diameter, LA volume
      index, peak A velocity, E/e', relative LV wall thickness, and mean peak systolic
      LV radial strain. Multivariate regression analysis indicated that LA volume index
      is defined as a strong predictor related to LDUTR. CONCLUSIONS: Late diastolic LV
      untwisting reduces with a gradual increase in the LA size in patients with
      cardiovascular risk factors, and may reflect the disease history of chronic LV
      diastolic dysfunction.

PMID- 20817412
TI  - Coping, productive time use, and negative mood among adults with severe mental
      illness: a daily diary study.
AB  - Most studies on coping among persons with severe mental illness have relied on
      retrospective self-report methods; a limitation of this methodology is
      susceptibility to recall bias. The purpose of the present investigation was to
      expand the current understanding of the impact of coping among persons with
      severe mental illness by examining coping strategies, mood, and social
      functioning (operationalized as productive time use) using a daily process
      design. Twenty-seven adults diagnosed with severe mental illness completed
      baseline clinical interviews and up to 20 days of nightly telephone interviews
      addressing coping and daily life. A total of 198 coping efforts were reported for
      387 days. Mixed-effects regression analyses examined the association between type
      of daily coping strategy (problem-centered, neutral, or avoidant) and both daily
      proportion of time participants spent in productive activity and daily negative
      mood, controlling for demographic and clinical variables. The results indicated
      that productive time use was significantly lower on days when avoidant strategies
      were used, in contrast with days when problem-centered strategies and neutral
      strategies were used. There was no significant main effect of coping on negative
      mood, although there was a trend in the expected direction. Findings support the
      hypothesis that the types of coping strategies adults with severe mental illness
      use are related to better social functioning on a daily level.

PMID- 20817413
TI  - The contributions of disease and genetic factors towards regional cortical
      thinning in schizophrenia: the UCLA family study.
AB  - OBJECTIVE: Cortical thickness reductions in prefrontal and temporal cortices have
      been repeatedly observed in patients with schizophrenia. However, it remains
      unclear whether regional variations in cortical thickness may be attributable to
      disease-related or genetic-liability factors. METHOD: The structural magnetic
      resonance imaging data of 48 adult-onset schizophrenia patients, 66 first-degree
      non-psychotic relatives of schizophrenia patients, 27 community comparison (CC)
      probands and 77 CC relatives were examined using cortical pattern matching
      methods to map and compare highly localized changes in cortical gray matter
      thickness between groups defined by biological risk for schizophrenia. RESULTS:
      Schizophrenia patients showed marked cortical thinning primarily in frontal and
      temporal cortices when compared to unrelated CC probands. Results were similar,
      though less pronounced when patients were compared with their non-psychotic
      relatives. Cortical thickness reductions observed in unaffected relatives
      compared to age-similar CC relatives suggestive of schizophrenia-related genetic
      liability were marginal, surviving correction for the left parahippocampal gyrus
      and inferior occipital cortex only. CONCLUSIONS: Observations of pronounced
      fronto/temporal cortical thinning in schizophrenia patients replicate prior
      findings. The lack of marked cortical thickness alterations in non-psychotic
      relatives of patients, suggests that disease processes are primary contributors
      toward cortical thickness reductions in the disorder. However, genetic factors
      may have a larger influence on abnormalities in the medial temporal lobe.

PMID- 20817414
TI  - Impaired insight in patients with newly diagnosed nonaffective psychotic
      disorders with and without deficit features.
AB  - Patients with schizophrenia who have primary, enduring negative symptoms, or the
      deficit syndrome, have poorer psychosocial functioning but lesser clinical
      distress compared with nondeficit patients. Poor awareness of impairment in
      patients with deficit schizophrenia may contribute to this seeming contradiction.
      We hypothesized that poor insight would be present early in the course of illness
      in deficit patients, and that those with deficit features would have greater
      impairment in insight than those without deficit features. One-hundred one first
      episode patients with nonaffective psychotic disorders were categorized into
      deficit (n=31) and nondeficit (n=70) groups. The deficit patients had
      significantly poorer insight than nondeficit patients when rated using a self
      report questionnaire, and nearly significantly poorer insight rated by clinical
      researchers. Further, this effect remained for self-rated insight and reached
      statistical significance for researcher-rated insight after controlling for
      positive, negative, and general psychopathology symptoms. These results suggest
      that the treatment of deficit patients may be particularly complicated by poor
      insight.

PMID- 20817415
TI  - Rotational echo double resonance without proton decoupling under fast spinning
      condition.
AB  - We show that rotational echo double resonance (REDOR) experiments can be carried
      out without proton decoupling under the conditions of fast spinning and strong rf
      field. Numerical simulations on a five-spin systems show that no significant
      attenuation of the reference signal (S(0)) is observed at a spin rate of 25 kHz,
      provided that the rf power is larger than 100 kHz. This approach has been
      validated by (31)P{(13)C} REDOR measurements on isotopically labeled glyphosate.
      The obtained van Vleck's second moment is in favorable agreement with the value
      calculated based on the crystal structure.

PMID- 20817416
TI  - Linkage scan of alcohol dependence in the UCSF Family Alcoholism Study.
AB  - Ample data suggest that alcohol dependence represents a heritable condition, and
      several research groups have performed linkage analysis to identify genomic
      regions influencing this disorder. In the present study, a genome-wide linkage
      scan for alcohol dependence was conducted in a community sample of 565 probands
      and 1080 first-degree relatives recruited through the UCSF Family Alcoholism
      Study. The Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) was
      used to derive DSM-IV alcohol dependence diagnoses. Although no loci achieved
      genome-wide significance (i.e., LOD score > 3.0), several linkage peaks of
      interest (i.e., LOD score > 1.0) were identified. When the strict DSM-IV alcohol
      dependence diagnosis requiring the temporal clustering of symptoms served as the
      phenotype, linkage peaks were identified on chromosomes 1p36.31-p36.22, 2q37.3,
      8q24.3, and 18p11.21-p11.2. When the temporal clustering of symptoms was not
      required, linkage peaks were again identified on chromosomes 1p36.31-p36.22 and
      8q24.3 as well as novel loci on chromosomes 1p22.3, 2p24.3-p24.1, 9p24.1-p23, and
      22q12.3-q13.1. Follow-up analyses were conducted by performing linkage analysis
      for the 12 alcohol dependence symptoms assessed by the SSAGA across the support
      intervals for the observed linkage peaks. These analyses demonstrated that
      different collections of symptoms often assessing distinct aspects of alcohol
      dependence (e.g., uncontrollable drinking and withdrawal vs. tolerance and
      drinking despite health problems) contributed to each linkage peak and often
      yielded LOD scores exceeding that reported for the alcohol dependence diagnosis.
      Such findings provide insight into how specific genomic regions may influence
      distinct aspects of alcohol dependence.

PMID- 20817417
TI  - The role of adverse events and related safety data in the pre-market evaluation
      of drug abuse potential.
AB  - The scientific and regulatory assessment of abuse and dependence potential of
      drugs involves a multi-layered evaluation of its properties related to chemistry,
      formulation, pharmacology, animal behavior and clinical response. In addition to
      the primary laboratory-based assessment in experienced drug users, data are also
      reviewed from studies in healthy volunteers and in the patient population. Much
      of the emphasis in these latter studies is placed on adverse events that are
      reported by the subject or observed by the investigator. Unlike other aspects of
      abuse potential assessment, the evaluation of abuse- and dependence-related
      events has not been the subject of scholarly research. The present commentary
      presents recommendations for several areas that would benefit from a consensus
      review to result in greater standardization for the analysis and presentation of
      abuse- and dependence-related data from clinical trials. These include special
      investigator training, a system of weighted primary and secondary terms,
      adjudication of individual events, case report management, organization of
      integrated safety data, and protocols for drug accountability. Such an effort
      would aid in implementing the evolving efforts of health authorities to guide
      drug developers in the collection and presentation of data needed for the
      regulation of drugs with the potential for abuse and dependence.

PMID- 20817418
TI  - Copper, zinc, cadmium and lead biosorption by Gymnogongrus torulosus.
      Thermodynamics and kinetics studies.
AB  - Gymnogongrus torulosus adsorption efficiency for cadmium(II), copper(II),
      lead(II) and zinc(II) were studied in batch mode in different acidic conditions.
      The adsorbent removal efficiency was determined as a function of contact time,
      initial metal ions concentration, pH and temperature. G. torulosus was
      characterized by SEM, water adsorption surface area and EDS. The Langmuir,
      Freundlich, Dubinin-Radushkevich and Temkin models have been applied and results
      showed that the biosorption process was better described by the Langmuir model.
      Kinetic experiments demonstrated that fast metal uptakes follow a pseudo-second
      order kinetic model and that intra-particle diffusion and/or chemisorption were
      the rate-limiting steps. Experimental results show that G. torulosus isotherm
      followed the biosorption series, Cu>Cd~Zn~Pb. Biosorption capacities were
      affected by solution parameters. The maximum metal uptake (qmax) increased with
      increasing pH. The affinity constant, qmax, and the pseudo-second-order kinetic
      constants were calculated for the adsorption of all studied metals onto G.
      torulosus. The Gibbs free energy of the adsorption process as well as the process
      enthalpy and entropy were calculated from experimental results.

PMID- 20817419
TI  - Characterization and biocompatibility of nanohybrid scaffold prepared via in situ
      crystallization of hydroxyapatite in chitosan matrix.
AB  - Hydroxyapatite (HAP) precursor solution was first mixed with an acetic acid
      chitosan (CS) solution. The mixture was then lyophilized to form the original
      scaffold, which stored the HAP precursors. The nano HAP crystallized
      homogeneously from the CS matrix during the alkaline treatment to form a
      nanohybrid scaffold. Scanning electron microscopy (SEM), X-ray diffraction (XRD),
      X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared
      spectroscopy (FTIR) were used to investigate the fabrication process of the
      nanohybrid scaffold. XRD results showed that the in situ deposited mineral (HAP)
      in the scaffold has phase structure similar to natural bone. FTIR and XPS results
      indicated that CS's hydroxyl group, amino and amide regulated the nano HAP
      crystallization process, which resulted in the nano homogeneous distribution of
      nano HAP and provided nano topographical features for the nanohybrid scaffold.
      MTT testing and SEM images of human bone mesenchymal stem cells (hBMSCs) cultures
      revealed the attachment and growth of hBMSCs in the biocomposite scaffold. Cell
      morphology and viability data showed that the nanohybrid composite scaffold is
      suitable for use in bioapplications.

PMID- 20817420
TI  - Physico chemical properties of aminated tamarind xyloglucan.
AB  - Tamarind xyloglucan (XG) has been functionalized with amino group, which forms
      irreversible hydrogels with blue fluorescence characteristics. Aminated
      xyloglucan (XG-NH2) at very low concentration (0.2%, w/v) in aqueous medium,
      forms self assembled spherical nano-particles of 60 nm size, where as at 7%
      (w/v), it formed a strong hydrogel. The bonding of amino group to the XG polymers
      was confirmed by FTIR spectra. The XG-NH2 has same solubility as XG. The XG
      showed a broad melting point around 78 degrees C whereas XG-NH2 was at 115
      degrees C. In addition, aminated xyloglucan (XG-NH2) exhibited good thermal
      properties. The XG-NH2 shows better antimicrobial activity in comparison to
      chitosan. This modified xyloglucan has potential applications in the medical and
      biotronics field because it possesses biocompatibility, strong hydrogel behavior
      with very useful blue fluorescence.

PMID- 20817421
TI  - Identification of novel immunogenic proteins in pathogenic Haemophilus parasuis
      based on genome sequence analysis.
AB  - Haemophilus parasuis causes contagious porcine Glasser's disease, which is
      occurring worldwide and leads to severe losses in the pig industry. To identify
      novel antigen candidates against this disease, 22 surface-exposed or secreted
      proteins were selected from the annotated H. parasuis genome by reverse
      vaccinology strategy. Expression of these proteins in Escherichia coli was
      attempted. Immunogenicity of the expressed candidates was assessed using Western
      blot analysis with mouse-derived antiserum prepared with whole bacteria of H.
      parasuis serovar 4 or 5. Three ABC-type transporters (OppA, YfeA and PlpA) and 1
      curli protein assembly (CsgG) were identified as potent immunogenic proteins. The
      proteins show cross-reactions when tested with sera raised against serovars 4 and
      5 of H. parasuis.

PMID- 20817422
TI  - Antimicrobial susceptibilities and population structure of Staphylococcus
      epidermidis associated with ovine mastitis.
AB  - Intramammary infections are a serious problem for dairy sheep farms, and
      Staphylococcus epidermidis is one of the main etiological agents of ovine
      mastitis. In this work, 131 S. epidermidis isolates, collected from 2201 dairy
      Sarda sheep belonging to 14 flocks with high somatic cell count scores, were
      studied. The flocks were located in diverse geographical areas of Sardinia,
      Italy. The aim of study was to assess the susceptibility of isolates to 13
      antimicrobial agents, many of which are frequently used in mastitis therapy.
      Oxacillin was used for detecting methicillin-resistant S. epidermidis (MRSE) by
      disk diffusion test. Thirty-eight percent of the isolates (n=50) were resistant
      to penicillin, 7.6% (n=10) were resistant to tetracycline, and 2.3% (n=3) were
      resistant to both penicillin and tetracycline (PTRSE). Two isolates were
      resistant to five antimicrobials including methicillin. Analysis of
      staphylococcal cassette chromosome mec (SCCmec) elements showed that both MRSE
      isolates harbored SCCmec type IVa. Based on pulsed-field gel electrophoresis
      (PFGE) typing by SmaI macrorestriction, S. epidermidis isolates were grouped into
      four clusters at 75% similarity level. The two multi-drug resistant MRSE isolates
      displayed distinct PFGE patters. This study indicates that S. epidermidis
      isolates from sheep milk samples may accumulate resistance markers for different
      antimicrobial agents. Furthermore, the occurrence of PTRSE and MRSE suggests to
      adopt adequate hygienic measures when handling animals with intramammary
      infections, in order to prevent spreading PTRSE and MRSE strains to humans
      through direct contact and/or consumption of contaminated food.

PMID- 20817423
TI  - [Lacrimal pathology in the infant and the child].
AB  - Tearing and lacrimal pathologies are very frequent motives of consultation. The
      pediatrician must know the congenital dacryocele, and nasolacrimal duct
      obstruction by the Hasner valve imperforation, which represents the main reason
      of tearing of the infant. Nasolacrimal duct obstruction is treated by probing by
      the ophthalmologist from the third month and by probing with silicone intubation
      in case of failure, or in the children of more than one year old.

PMID- 20817424
TI  - Maternal diet during pregnancy has tissue-specific effects upon fetal fatty acid
      composition and alters fetal immune parameters.
AB  - Both animal and human studies demonstrate that the docosahexaenoic acid (DHA)
      content of plasma and/or tissue lipids is increased during pregnancy. We
      hypothesised that increasing the alpha-linolenic acid (ALA) or longer chain (n-3)
      PUFA content of the maternal diet during pregnancy influences fetal fatty acid
      composition and the fetal immune system. Pregnant rats were fed a low-fat (LF)
      soybean oil diet, or high-fat (HF) soybean, linseed, salmon or sunflower oil
      diets from conception to 20d gestation. The ALA-rich Linseed-HF diet resulted in
      an equivalent eicosapentaenoic acid (EPA) status in fetal immune tissues and an
      equivalent DHA status in the fetal brain to that achieved with the Salmon-HF
      diet. An (n-3) rich maternal diet during pregnancy associated with the highest
      expression of CD3 (Salmon-HF) and CD8 (Linseed-HF and Salmon-HF) on fetal thymic
      CD3(+)CD8(+) cells. The Linseed-HF diet resulted in the highest proportion of
      CD161(+) cells within the fetal thymus, which correlated with the production of
      IL-4. These data indicate that dietary ALA supplementation may confer some of the
      benefits of LC (n-3) PUFA during pregnancy. This should be examined in suitably
      designed human studies.

PMID- 20817425
TI  - Repression of early zygotic transcription in the germline.
AB  - Germ cells, the progenitors of gametes, are often specified and segregated from
      somatic lineages early in embryogenesis. As germ cells are essential to create
      the next generation in sexually reproducing organisms, they must be prevented
      from differentiating inappropriately into somatic cells. In Drosophila and
      Caenorhabditis elegans embryos, this is governed by the transient and global
      repression of mRNA transcription. Furthermore, the inhibition of somatic
      transcriptional programs is also crucial for germ cell specification in the
      mouse. Therefore, the active repression of somatic transcriptional programs
      appears to be a common mechanism for launching the germline. In this review, we
      will discuss the mechanisms of transcriptional repression during germ cell
      specification and their interspecies similarities and differences.

PMID- 20817426
TI  - Born to run: creating the muscle fiber.
AB  - From the muscles that control the blink of your eye to those that allow you to
      walk, the basic architecture of muscle is the same: muscles consist of bundles of
      the unit muscle cell, the muscle fiber. The unique morphology of the individual
      muscle fiber is dictated by the functional demands necessary to generate and
      withstand the forces of contraction, which in turn leads to movement. Contractile
      muscle fibers are elongated, syncytial cells, which interact with both the
      nervous and skeletal systems to govern body motion. In this review, we focus on
      three key cell-cell and cell-matrix contact processes, that are necessary to
      create this exquisitely specialized cell: cell fusion, cell elongation, and
      establishment of a myotendinous junction. We address these processes by
      highlighting recent findings from the Drosophila model system.

PMID- 20817428
TI  - Dynamics of endothelial cell behavior in sprouting angiogenesis.
AB  - The vertebrate body contains an extensive blood vessel network that forms, with a
      few exceptions, by endothelial sprouting from the existing vasculature. This
      process, termed angiogenesis, involves complex and highly dynamic interactions
      between endothelial cells and their environment. Pro-angiogenic signals, such as
      VEGF, promote endothelial motility, filopodia extension and proliferation, and,
      together with Notch signaling, controls whether specific endothelial cells become
      lead tip cells or trailing stalk cells. Sprouts then convert into endothelial
      tubules and form connections with other vessels, which requires the local
      suppression of motility and the formation of new cell-cell junctions. We here
      review the dynamics of angiogenesis in the context of key molecules and pathways
      controlling tip cell selection, sprouting and the formation of new vessels.

PMID- 20817427
TI  - Molecular cell death platforms and assemblies.
AB  - Multi-cellular animals have evolved a variety of mechanisms to respond to diverse
      apoptotic stimuli. In general these proceed through activation of apical caspases
      and culminate in executioner caspase activation and cell death. Because of the
      breadth of possible initiators, various molecular platforms are used to trigger
      different apical caspases. Although some common protein domains are used to
      assemble the apoptosome, the PIDDosome and death receptor complexes, an array of
      checks-and-balances are employed to ensure appropriate activation.
      Notwithstanding, these pathways share the underlying principle of proximity
      dependent activation and post-translational modification. Here we will describe
      our current structural understanding of assembly and regulation of these
      signaling platforms.

PMID- 20817429
TI  - Intratympanic dexamethasone as initial therapy for idiopathic sudden
      sensorineural hearing loss: Clinical evaluation and laboratory investigation.
AB  - OBJECTIVE: To evaluate the effect of intratympanic dexamethasone (ITD) as initial
      therapy for idiopathic sudden sensorineural hearing loss (ISSHL) as well as to
      determine the concentration-dependent time course distribution of dexamethasone
      in the inner ear. METHODS: Sixty-six patients with profound ISSHL were included.
      Twenty-two were treated with ITD and the rest as control. Audiograms were
      performed before the treatment and one month afterwards. In the animal study,
      dexamethasone of different concentrations (5, 10 and 20mg/ml) was injected into
      the tympanums of three groups of SD rats (Groups A, B and C), their inner ears
      dissected free at various postinjection survival intervals. Immunofluorescence
      was applied to detect the locations of dexamethasone. RESULTS: The overall rate
      of good prognosis was 77.27% in ITD group, which was not significantly different
      from 81.82% in the control group. In the animal study, the higher local
      concentration and longer lasting period was found in Groups B and C. CONCLUSIONS:
      ITD at 5mg/ml did not add effect to systemic steroids in improving hearing
      outcomes in patients with ISSHL. An increase in dexamethasone concentration led
      to large variations in pharmacokinetics in animal study, showing potential value
      in optimizing the drug delivery protocols and improving the therapeutic results.

PMID- 20817431
TI  - Environmental friendly leaching reagent for cobalt and lithium recovery from
      spent lithium-ion batteries.
AB  - We investigated an environmentally friendly leaching process for the recovery of
      cobalt and lithium from the cathode active materials of spent lithium-ion
      batteries. The easily degradable organic acid DL-malic acid (C(4)H(5)O(6)) was
      used as a leaching reagent. The structural, morphology of the cathode materials
      before and after leaching were characterized by X-ray diffraction (XRD) and
      scanning electronic microscopy (SEM). The amount of Co and Li present in the
      leachate was determined by atomic absorption spectrophotometry (AAS). Conditions
      for achieving a recovery of more than 90 wt.% Co and nearly 100 wt.% Li were
      determined experimentally by varying the concentrations of leachant, time and
      temperature of the reaction as well as the initial solid-to-liquid ratio. We
      found that hydrogen peroxide in a DL-malic acid solution is an effective reducing
      agent because it enhances the leaching efficiency. Leaching with 1.5M DL-malic
      acid, 2.0 vol.% hydrogen peroxide and a S:L of 20 g L(-1) in a batch extractor
      results in a highly efficient recovery of the metals within 40 min at 90  degrees
      C.

PMID- 20817430
TI  - Epidemiological analysis of nasopharyngeal carcinoma in the central region of
      Japan during the period from 1996 to 2005.
AB  - OBJECTIVE: It has become clear through epidemiological analysis that the
      incidence of cancers of the lung, liver, colon, and rectum are increasing in
      Japan every year. However, there have been few epidemiological analyses of
      nasopharyngeal carcinoma (NPC) in Japan. The aim of this study was to analyze the
      epidemiology and current incidence of NPC in the Chubu region of Japan during the
      period from 1996 to 2005. METHODS: Takeshita et al. conducted a similar
      investigation in the Chubu region 10 years ago, and, as a result, this is a
      comparative study. The Chubu region is the central region of Japanese main
      island. We researched NPC patients treated in hospitals in each prefecture over a
      10-year period (1996-2005) using a questionnaire. RESULTS: A total of 525 cases
      (male:385, female:134, unknown:6) were analyzed epidemiologically,
      histologically, serologically, and clinically in this study. The incidence per
      10(5) population per year was 0.29. For the period of 1986-1995, the age
      standardized incidence of NPC was 0.28 per 10(5) persons per year in Takeshita's
      report. There was no significant difference between the two periods. The ages of
      the patients ranged from 13 to 90 years. The mean age of was 55.2 years. On the
      basis of the World Health Organization (WHO) histological criteria, 36% of the
      patients were classified as WHO I, 27% as WHO II, and 37% as WHO III. Carcinoma
      was located in the posterosuperior region in 56%, lateral in 41%, and inferior in
      3%. Tumor staging showed that 6% to belonged to stage I, 25% to stage II, 31% to
      stage III, and 38% to stage IV. A neck mass was present in 52% of the patients,
      ear symptoms in 48%, nasal symptoms in 27%, headaches in 10%, pharyngeal symptoms
      in 9%, ophthalmologic symptoms in 9%, and cranial neurological symptoms in 9%.
      The positive rates of serum titers of the antibodies to Epstein-Barr virus (EBV)
      related antigens were calculated. The positive rate of anti-EBV-viral capsid
      antigen (VCA) immunoglobulin (Ig) G titers was 58.6%, that of anti-EBV-VCA IgA
      titers was 53.6%, and that of EBNA was 81%. The five-year survival rate for all
      patients was 67.6%, and that for those in stage I, II, III, and IV was 75%, 84%,
      69%, and 53%, respectively. The five-year survival rate for stage IV was
      significantly lower than those for the other stages (P<0.05). CONCLUSION: The age
      standardized annual incidence of NPC in our survey was 0.29 per 10(5) persons per
      year, being relatively low and stable.

PMID- 20817432
TI  - Electroclinical findings in four patients with karyotype 47,XYY.
AB  - 47,XYY karyotype is a Y chromosome aneuploidy characterized by an extra copy of
      the Y chromosome in each of the male cells, with an incidence of 1/1000 males.
      Most studies about 47,XYY have focused on growth, cognitive development, academic
      performance, behavioural problems, speech and language skills and neuromuscular
      status. Up-to-date reports on seizures and EEG characteristics concerning 47,XYY
      men have been sporadic and poorly detailed. The aim of this study is to describe
      the particular electroclinical patterns in a group of four subjects with 47,XYY
      karyotype. We performed neurological examinations, psychometric tests, brain
      MRIs, prolonged EEG recordings during awake and sleep on four unselected males
      47,XYY. All four patients presented various degrees of neuropsychological
      impairment. An incidence of familial antecedents for epilepsy was confirmed by
      three families. When present, seizures were very similar to that of benign
      epilepsy with central-temporal spikes, (BECTS), for age of onset, clinical
      picture, evolution and good response to antiepileptic drugs. EEG recordings in
      all four subjects showed normal background activity and sleep organization,
      particular focal spikes and sharp-waves localized mostly over the vertex and/or
      central-temporal regions, which increased during sleep. In our opinion, these
      47,XYY patients present a particular electroclinical pattern.

PMID- 20817433
TI  - Benign nocturnal alternating hemiplegia of childhood: two cases with positive
      evolution.
AB  - Benign nocturnal alternating hemiplegia (BNAH) of childhood is distinct from the
      classic form of malignant alternating hemiplegia of childhood [1]. It is
      characterized by hemiplegic attacks occurring exclusively during sleep [2]. It
      can be misdiagnosed as migraine, nocturnal frontal lobe epilepsy, benign rolandic
      epilepsy, Panayiotopoulos syndrome, or sleep-related movement disorder [1-4].
      Only nine patients have been described to date, with typically, a normal
      development [1,5-7]. In order to insist about the benignity of the affection, we
      report two cases: a new three-year-old boy suffering from BNAH and a patient
      already published to show positive evolution at fourteen years of age. BNAH is a
      rare disorder but may be underdiagnosed. Making an early diagnosis can help to
      describe to the parents the good prognosis without treatment.

PMID- 20817435
TI  - In vitro evaluation of 56 coronary artery stents by 256-slice multi-detector
      coronary CT.
AB  - OBJECTIVE: We sought to investigate stent lumen visibility of 56 coronary stents
      with the newest 256-multi-slice-CT (256-MDCT) technology for different
      reconstruction algorithms in an in vitro model. BACKGROUND: Early identification
      of in-stent restenosis (ISR) is important to avoid recurrent ischemia and prevent
      acute myocardial infarction (AMI). Since angiography has the disadvantage of high
      costs and its invasiveness, MDCT could be a convenient and safe non-invasive
      alternative for detection of ISR. MATERIAL AND METHODS: Percentages of in-stent
      lumen diameter and in-stent signal attenuation (measured as contrast-to-noise
      ratio (CNR)) of 56 coronary stents (group A <=2.5mm; group B=2.75-3.0mm; group
      C=3.5-4.0mm) were evaluated in a coronary vessel in vitro phantom (iodine-filled
      plastic tubes) employing four different reconstruction algorithms (XCD, CC, CD,
      XCB) on a novel 256-MDCT (Philips-iCT, collimation=128 mm * 0.625 mm; rotation
      time=270 ms; tube current=800 mAs with 120 kV). Analysis was conducted with the
      semi-automatical full-width-at-half-maximum (FWHM) method. P-values <0.05 were
      regarded statistically significant. RESULTS: In-stent lumen diameter >60% for
      group C stents was significantly larger and CNR was significantly lower (both
      p<0.05) for sharp kernels (CD; XCD) when compared to groups A/B. The FWHM-method
      showed significantly smaller in-stent lumen diameter (p<0.05) when compared to
      the manual method. CONCLUSION: 256-MDCT could potentially be employed for
      clinical assessment of stent patency in stents >3.0mm when analysed with cardio
      dedicated sharp kernels, although clinical studies corroborating this claim
      should be performed. However, stents <=3.0mm reconstructed by soft kernels
      revealed insufficient in-stent lumen visualisation and should not be used in
      clinical practice. Further improvements in spatial and temporal image resolution
      as well as reductions of radiation exposure and image noise have to be
      accomplished for the ambitious goal of characterising both CT coronary artery
      anatomy and in-stent lumen.

PMID- 20817434
TI  - Small peptide recognition sequence for intracellular sorting.
AB  - Increasing evidence indicate that complex arrays of short signals and recognition
      peptide sequence ensure accurate trafficking and distribution of transmembrane
      receptors and/or proteins and their ligands into intracellular compartments.
      Internalization and subsequent trafficking of cell-surface receptors into the
      cell interior is mediated by specific short-sequence peptide signals within the
      cytoplasmic domains of these receptor proteins. The short signals usually consist
      of small linear amino acid sequences, which are recognized by adaptor coat
      proteins along the endocytic and sorting pathways. In recent years, much has been
      learned about the function and mechanisms of endocytic pathways responsible for
      the trafficking and molecular sorting of membrane receptors and their ligands
      into intracellular compartments, however, the significance and scope of the short
      sequence motifs in these cellular events is not well understood. Here a
      particular emphasis has been given to the functions of short-sequence signal
      motifs responsible for the itinerary and destination of membrane receptors and
      proteins moving into subcellular compartments.

PMID- 20817436
TI  - Dosimetric comparison of manual and beam angle optimization of gantry angles in
      IMRT.
AB  - Dosimetric comparison of manual beam angle selection (MBS) and beam angle
      optimization (BAO) for IMRT plans is investigated retrospectively for 15 head and
      neck and prostate patients. The head and neck and prostate had planning target
      volumes (PTVs) ranging between 96.0 and 319.9 cm(3) and 153.6 and 321.3 cm(3),
      whereas OAR ranged between 8.3 and 47.8 cm(3) and 68.3 and 469.2 cm(3),
      respectively. In MBS, a standard coplanar 7-9 fields equally spaced gantry angles
      were used. In BAO, the selection of gantry angle was optimized by the algorithm
      for the same number of beams. The optimization and dose-volume constraints were
      kept the same for both techniques. Treatment planning was performed on the
      Eclipse treatment planning system. Our results showed that the dose-volume
      histogram for PTV are nearly identical in both techniques but BAO provided
      superior sparing of the organs at risk compared with the MBS. Also, MBS produced
      statistically significant higher monitor units (MU) and segments than the BAO;
      13.1 +/- 6.6% (p = 0.012) and 10.4 +/- 13.6% (p = 0.140), and 14.6 +/- 5.6% (p =
      1.003E-5) and 12.6 +/- 7.4% (p = 0.76E-3) for head and neck and prostate cases,
      respectively. The reduction in MU translates into the reduction in total body and
      integral dose. It is concluded that BAO provides advantage over MBS for most
      intenisty-modulated radiation therapy cases.

PMID- 20817437
TI  - Update of the All-Species Living Tree Project based on 16S and 23S rRNA sequence
      analyses.
AB  - The "All-Species Living Tree Project" (LTP) provides the scientific community
      with a useful taxonomic tool consisting of a curated database of type strain
      sequences, a universal and optimized alignment and a single phylogenetic tree
      harboring all the type strains of the hitherto classified species. On the website
      http://www.arb-silva.de/projects/living-tree an update has been regularly
      maintained by including the 1301 new descriptions that have appeared in the
      validation and notification lists of the IJSEM journal. The topology of the 16S
      rRNA-based tree was validated with a detailed comparison against a collection of
      taxa-specific and broad-range trees made using different approaches, subsets of
      sequences and alignments. Seven percent of the classified species is still
      missing, as their type strains do not have a good quality SSU sequence. In
      addition, a new database of type strains for which adequate 23S rRNA entries
      existed in public repositories was built. Among the 8602 species with validly
      published names until February 2010, we were able to find good quality LSU
      representatives for 792 type strains, whereas around 91% of the complete
      catalogue still remains unsequenced. Despite the scarce representation of some
      groups in LSU databases, we have devised a highly optimized alignment and a
      reliable LSU tree in order to set up a stable phylogenetic starting point for
      taxonomic purposes. The current release corresponds to the fourth update of the
      project (LTPs102), and contains additional features which increase usability and
      compatibility. Use the contact address living-tree@arb-silva.de to provide
      additional input for the development of this taxonomic tool.

PMID- 20817438
TI  - Microglia in the developing brain: from immunity to behaviour.
AB  - For decades, microglia, the resident macrophages of the brain, have been
      recognized mostly for their role in several, if not all, pathologies affecting
      the brain. However, several studies under physiological conditions demonstrate
      that microglial function is indispensable also in the healthy brain. Indeed,
      microglia implement key functions already during development, such as the
      clearance of the huge amount of neurons that are produced in large excess in the
      embryo and later die of apoptosis. Beside these classical functions, however,
      novel roles are emerging that strikingly link microglia with higher order brain
      functions and show that these cells can ultimately influence behaviour. Therefore
      a detailed understanding of microglia under physiological conditions may open
      unprecedented perspectives in the prevention and treatment of neuropsychiatric
      diseases.

PMID- 20817439
TI  - Reversal of myo-inositol metabolic level in the left dorsolateral prefrontal
      cortex of rats exposed to forced swimming test following desipramine treatment:
      an in vivo localized (1)H-MRS study at 4.7 T.
AB  - The forced swimming test (FST) is a useful paradigm that is relatively quick and
      simple to perform and has been utilized to predict antidepressant activity based
      on learned helplessness as a model of depression. To date, few studies have used
      proton magnetic resonance spectroscopy ((1)H-MRS) to assess antidepressant
      effects in rats. The purpose of this study was to assess desipramine (DMI)
      effects on the left dorsolateral prefrontal cortex (DLPFC) of the rats, which
      were randomly assigned to three groups (control, n=10; FST+saline, n=10; FST+DMI,
      n=10), using single-voxel localization technique. All (1)H-MRS experiments were
      performed on a Bruker 4.7-T scanner with 400 mm bore magnet, allowing for
      acquisition of in vivo (1)H point-resolved spectroscopy spectra (TR/TE=3000/30
      ms, number of data points=2048, NEX=512, voxel volume=27 MUl, scan time=25 min).
      Proton metabolites were quantified automatically using LCModel software and were
      expressed as ratios to total creatine (Cr+PCr). Major target metabolites such as
      N-acetyl aspartate (NAA)+N-acetylaspartylglutamate (NAAG), glutamate+glutamine
      (Glu+Gln), glycerophosphorylcholine+phosphorylcholine (GPC+PCho), myo-inositol
      (mIns) and taurine (Tau) were successfully quantified with Cramer-Rao lower
      boundary <=10%. There were significantly higher mIns/(Cr+PCr) and mIns/(NAA+NAAG)
      ratios in the FST+saline group compared to the control group. In the FST+DMI
      group, both mIns/(Cr+PCr) and mIns/(NAA+NAAG) ratios were significantly decreased
      to the level similar to those in the control group. No other metabolite ratios
      were significantly different among the three groups. Our findings suggest a
      possible role of altered mIns level within the left DLPFC of the rat model for
      depression.

PMID- 20817440
TI  - Analysis of time reduction methods for magnetic resonance elastography of the
      brain.
AB  - Magnetic resonance elastography (MRE) uses a phase-contrast MRI technique to
      image shear wave propagation in tissue followed by the mathematical inversion of
      the equations of motion governing tissue mechanics to noninvasively image tissue
      stiffness. This work investigates the impact of various MR sampling strategies
      designed to reduce acquisition times on the accuracy of MRE inversions. The
      results indicate that brain MRE data can be significantly truncated while
      maintaining a mean global stiffness error less than 10%. The results also
      indicate that brain MRE data can be collected in as few as eight lines of k
      space. This degree of data truncation is possible due to the relatively low
      spatial frequency content and low amplitude of the shear waves observed during
      brain MRE exams and will facilitate the design of rapid brain MRE protocols for
      future clinical investigations.

PMID- 20817441
TI  - Alkaline and alkaline/oxidation pre-treatments of spruce wood (Picea abies)-
      impact on the quality of kraft pulp.
AB  - A comparable series of specimens from spruce wood were pre-treated with sodium
      hydroxide, sodium hydroxide and hydrogen peroxide, or per-acetic acid sequences.
      The pre-treatments reduced the yield of pulps and their Kappa number noticeably,
      diminished the degree of polymerization moderately, and increased their
      brightness. One-step peroxide bleaching of pulps from the pre-treated spruce wood
      resulted in their higher brightness compared to bleached pulp from sound wood.
      From the viewpoint of improved properties of pulp, the most efficient were the
      sodium hydroxide/per-acetic acid and per-acetic acid/sodium hydroxide sequences.
      The pre-treatments did not influence mechanical strength of the obtained pulps
      significantly.

PMID- 20817442
TI  - Effect of prolonged hypoxia in autotrophic conditions in the hydrogen production
      by the green microalga Chlamydomonas reinhardtii in photobioreactor.
AB  - In the context of hydrogen production by the green alga Chlamydomonas
      reinhardtii, the control of light attenuation conditions is used to set-up anoxia
      under illuminated and autotrophic conditions, without affecting photosynthetic
      capacities of cells (as with sulphur deprivation or PSII inhibitors like DCMU).
      This paper presents a full description of the protocol where the incident photons
      flux density (PFD) is adapted during cultivation in order to obtain a
      sufficiently low illuminated fraction gamma under 0.25 leading to anoxic hydrogen
      producing conditions during several days. The protocol is validated in a torus
      shape photobioreactor (PBR) revealing after few days of anoxic conditions a peak
      of hydrogen production (1.44 ml H2/h/l of culture; [0.8-1.0] ml H2/h/g of dry
      weight biomass) concomitant with a decrease of biomass concentration, protein
      content and maximal photosynthetic yield. Effect of over-accumulating starch, as
      being known to increase hydrogen production by the PSII-independent pathway, is
      also investigated.

PMID- 20817443
TI  - Antibiotic resistance profiles and virulence markers of Pseudomonas aeruginosa
      strains isolated from composts.
AB  - The aim of our work was to determine the presence of Pseudomonas aeruginosa in
      compost raw materials, immature and mature compost, and compost-treated soil.
      Twenty-five strains of P. aeruginosa were isolated from a raw material (plant
      straw), immature and mature compost and compost-treated soil samples. The strains
      were identified using the PCR method for the detection of species specific
      variable regions of 16S rDNA. Strains were examined for the presence of five
      different virulence-related gene sequences (exoA, exoU, exoT, exoS and exoY) and
      their antibiotic resistance profiles were determined. Based on our results,
      species P. aeruginosa can reach significant numbers (up to 10(6) MPN/g sample)
      during composting and 92.0% of the isolated strains carrying at least two gene
      sequences encoding toxic proteins. Various types of drug resistance were detected
      among compost originating strains, mainly against third generation Cephalosporins
      and Carbapenems. Six isolates were able to resist two different classes of
      antibiotics (third generation Cephalosporins and Carbapenems, wide spectrum
      Penicillins or Aminoglycosides, respectively). Based on our results, composts can
      be a source of P. aeruginosa and might be a concern to individuals susceptible to
      this opportunistic pathogen.

PMID- 20817444
TI  - Development of a simultaneous partial nitrification and anaerobic ammonia
      oxidation process in a single reactor.
AB  - Up-flow oxygen-controlled biofilm reactors equipped with a non-woven fabric
      support were used as a single reactor system for autotrophic nitrogen removal
      based on a combined partial nitrification and anaerobic ammonium oxidation
      (anammox) reaction. The up-flow biofilm reactors were initiated as either a
      partial nitrifying reactor or an anammox reactor, respectively, and simultaneous
      partial nitrification and anammox was established by careful control of the
      aeration rate. The combined partial nitrification and anammox reaction was
      successfully developed in both biofilm reactors without additional biomass
      inoculation. The reactor initiated as the anammox reactor gave a slightly higher
      and more stable mean nitrogen removal rate of 0.35 (+/-0.19) kg-N m(-3) d(-1)
      than the reactor initiated as the partial nitrifying reactor (0.23 (+/-0.16) kg-N
      m(-3) d(-1)). FISH analysis revealed that the biofilm in the reactor started as
      the anammox reactor were composed of anammox bacteria located in inner anoxic
      layers that were surrounded by surface aerobic AOB layers, whereas AOB and
      anammox bacteria were mixed without a distinguishable niche in the biofilm in the
      reactor started as the partial nitrifying reactor. However, it was difficult to
      efficiently maintain the stable partial nitrification owing to inefficient
      aeration in the reactor, which is a key to development of the combined partial
      nitrification and anammox reaction in a single biofilm reactor.

PMID- 20817445
TI  - Fluidized bed gasification of select granular biomaterials.
AB  - Biomaterials can be converted into solid, liquid and gaseous fuels through
      thermochemical or biochemical conversion processes. Thermochemical conversion of
      granular biomaterials is difficult because of its physical nature and one of the
      suitable processes is fluidized bed gasification. In this study, coir pith, rice
      husk and saw dust were selected and synthetic gas was generated using a fluidized
      bed gasifier. Gas compositions of product gas were analyzed and the percentage of
      carbon monoxide and carbon dioxide was in the range of 8.24-19.55 and 10.21
      17.14, respectively. The effect of equivalence ratio (0.3, 0.4 and 0.5) and
      reaction time (at 10 min interval) on gas constituents was studied. The gas yield
      for coir pith, rice husk and sawdust were found to be in the range of 1.98-3.24,
      1.79-2.81 and 2.18-3.70 Nm3 kg(-1), respectively. Models were developed to study
      the influence of biomaterial properties and operating conditions on molar
      concentration of gas constituents and energy output.

PMID- 20817447
TI  - Optimization and validation of the micellar electrokinetic capillary
      chromatographic method for simultaneous determination of sulfonamide and
      amphenicol-type drugs in poultry tissue.
AB  - The report describes a new approach enabling simple and rapid multi-residue
      screening of seven sulfonamides (SAs): sulfamethazine (SMZ), sulfamerazine (SMR),
      sulfathiazole (STZ), sulfachloropyridazine (SCP), sulfamethoxazole (SMX),
      sulfacarbamide (SC), and sulfaguanidine (SG); and three amphenicol-type
      antibiotics: chloramphenicol (CAP), thiamphenicol (TAP), and florfenicol (FF) in
      animal tissue by micellar electrokinetic chromatography (MEKC). The analytes were
      isolated from tissue samples through solid-phase extraction (with a C(18)
      cartridges) following protein precipitation with acetonitrile. The evaluated LOD
      and LOQ values ranged from 1.3 to 7.8 and from 4.5 to 26.1 ng/g, respectively.
      These values are far lower than the maximum residue limits (MRLs) set by several
      control authorities. Intra- and inter-day precision data were less than 9.5% and
      11.2% for SAs, and 8.4% and 14.9% for amphenicols. Moreover, the method was found
      accurate, with the recoveries ranging from 86.4% to 109.4%. The absolute
      recoveries of the analysed drugs were higher than 77.2%. The results obtained in
      the validation process demonstrate that the developed CE method is suitable for
      simultaneous determination of SA and amphenicol residues in poultry tissue, with
      the total run time less than 8 min.

PMID- 20817446
TI  - High-rate nitrogen removal by the anammox process at ambient temperature.
AB  - The purpose of this study is to investigate the nitrogen removal performance of
      the anaerobic ammonium oxidation (Anammox) process and the microbial community
      that enables the Anammox system to function well at ambient temperatures. A
      reactor with a novel spiral structure was used as the gas-solid separator. The
      reactor was fed with synthetic inorganic wastewater composed mainly of NH4+-N and
      NO2--N, and operated for 92 days. Stable nitrogen removal rates (NRR) of 16.3 and
      17.5 kg-N m(-3) d(-1) were obtained at operating temperatures of 33+/-1 and 23+/
      2 degrees C, respectively. To our knowledge, such a high NRR at ambient
      temperatures has not been reported previously. In addition, the experiments
      presented herein confirm that high influent NO2--N concentration of 460 mg L(-1)
      did not noticeably inhibit the Anammox activity. Furthermore, the freshwater
      Anammox bacterium KU2, which was identified as the dominant bacterial species in
      the consortium by 16S rRNA gene analysis, is considered to be responsible for the
      stable nitrogen removal performance at ambient temperatures.

PMID- 20817448
TI  - Measurement of cyclooxygenase inhibition using liquid chromatography-tandem mass
      spectrometry.
AB  - Because cyclooxygenases (COX) convert arachidonic acid into pro-inflammatory
      cyclic endoperoxides, inhibition of these enzymes and especially the inducible
      COX-2 form is an important therapeutic approach to manage inflammatory diseases
      and possibly prevent cancer. Due to side effects of existing non-selective and
      COX-2 selective non-steroidal anti-inflammatory agents, the discovery of new COX
      inhibitors continues to be an area of active investigation. Since existing assays
      are slow or lack specificity, a liquid chromatography-tandem mass spectrometry
      (LC-MS-MS) based COX inhibition assay was developed and validated for the rapid
      and accurate quantitative analysis of the COX product prostaglandin E(2). The
      assay was validated using four COX inhibitors, celecoxib, indomethacin,
      resveratrol, and diclofenac that exhibit different selectivities towards COX-1
      and COX-2. The IC(50) values of celecoxib and resveratrol for ovine and human COX
      2 were compared, and the K(m) values were determined. Since considerable inter
      species variation was observed, human COX-2 should be used for the discovery of
      COX inhibitors intended for human use. This sensitive and accurate LC-MS-MS based
      assay is suitable for the rapid screening of ligands for COX-1 and COX-2
      inhibition and for IC(50) determinations.

PMID- 20817449
TI  - 4-methylpteridinones as orally active and selective PI3K/mTOR dual inhibitors.
AB  - Pteridinones were designed based on a non-selective kinase template. Because of
      the uniqueness of the PI3K and mTOR binding pockets, a methyl group was
      introduced to C-4 position of the peteridinone core to give compounds with
      excellent selectivity for PI3K and mTOR. This series of compounds were further
      optimized to improve their potency against PI3Kalpha and mTOR. Finally, orally
      active compounds with improved solubility and robust in vivo efficacy in tumor
      growth inhibition were identified as well.

PMID- 20817450
TI  - Fatty acid synthase inhibitors of phenolic constituents isolated from Garcinia
      mangostana.
AB  - Natural inhibitors of fatty acid synthase (FAS) are emerging as potential
      therapeutic agents to treat cancer and obesity. The bioassay-guided chemical
      investigation of the hulls of Garcinia mangostana led to the isolation of 13
      phenolic compounds (1-13) mainly including xanthone and benzophenone, in which
      compounds 7, 8, 9, 10, and 11 were isolated from this plant for the first time
      and compound 9 was a new natural product. These isolates possess strong
      inhibitory activity of FAS with the IC(50) values ranging from 1.24 to 91.07 MUM.
      The study indicates that two types of natural products, xanthones and
      benzophenones, could be considered as promising FAS inhibitors.

PMID- 20817451
TI  - Alteration of cross-linking selectivity with the 2'-OMe analogue of 2-amino-6
      vinylpurine and evaluation of antisense effects.
AB  - We previously reported that oligodeoxynucleotides containing 2-amino-6
      vinylpurine (2-AVP: 1) exhibit efficient selective cross-linking to cytosine. In
      this study, the 2'-OMe nucleoside analogue (2) of 2-AVP was designed in order to
      increase its affinity to RNA and enhance metabolic stability. It has been
      demonstrated that 2'-OMe oligonucleotides bearing 2 achieve highly selective
      cross-linking to the thymine base in DNA and show higher antisense effect on
      luciferase production in cell lysate.

PMID- 20817452
TI  - Standardized Patient Instructor (SPI) interactions are a viable way to teach
      medical students about health behavior counseling.
AB  - OBJECTIVES: We explored comfort levels of third-year medical (M3) students
      through two health behavior counseling (HBC) interactions with Standardized
      Patient Instructors (SPIs) in tobacco cessation (TCC) and nutrition and physical
      activity (NPA). METHODS: Nearly 200 M3s participated in two SPI HBC interactions;
      including a role-play interview and subsequent feedback session on performance.
      Students completed a 5-point Likert scale evaluation measuring pre- and post
      comfort level on two HBC sessions. RESULTS: Both interactions resulted in
      statistically significant increases in student's pre- and post-interaction
      comfort levels. A paired-sample t-test revealed a mean increase of 0.91 for TCC
      (t = 14.01, df = 197, p<0.001), and a mean increase of 0.69 for NPA (t = 12.65,
      df = 198, p<0.001). CONCLUSION: The use of SPIs is a viable approach to exposing
      medical students and future doctors to health behavior counseling, and increasing
      comfort level with such skills. The SPI experience ensures that HBC opportunities
      are available and contain meaningful feedback on performance. PRACTICE
      IMPLICATIONS: Encouraging patient behavior modification is a skill that can be
      developed during undergraduate medical training. Combining HBC with SPI sessions
      and traditional learning approaches could prove effective in a curriculum
      intended to teach students strategies that improve patient health behavior.

PMID- 20817453
TI  - Preferences and experiences of chronically ill and disabled patients regarding
      shared decision-making: does the type of care to be decided upon matter?
AB  - OBJECTIVE: (1) To describe the importance chronically ill and disabled patients
      attach to involvement in decision-making when various care types are considered,
      and (2) to analyse the degree to which these patients are involved in shared
      decision-making (SDM) regarding these care types, and whether their involvement
      reflects the importance they attach to SDM. METHODS: The study sample consisted
      of 812 chronically ill and disabled patients who experienced a situation of
      decision-making during the last year. Data were collected by a self-report survey
      in 2006 and were analysed by multilevel linear regression analyses. RESULTS:
      Participants attached most importance to SDM when occupational healthcare issues
      were at stake, but perceived their actual involvement in these decisions as
      relatively low. Patients dealing with decision-making regarding medical care or
      home care experienced higher levels of involvement. The importance attached to
      SDM corresponds moderately with the actual role patients experience in the
      decision-making process. CONCLUSION: The type of care to decide upon impacts on
      the importance patients attach to SDM as well as on their actual involvement in
      decision-making. PRACTICE IMPLICATIONS: We suggest healthcare practitioners to
      pay attention to the preferred level of patient involvement each time a new care
      issue has to be decided upon.

PMID- 20817454
TI  - Quantitative ultrasound using backscatter analysis in Duchenne and Becker
      muscular dystrophy.
AB  - Evaluation of ultrasound images of muscle with calibrated muscle backscatter
      (cMB) provides reproducible quantitative measurements of muscle pathology.
      Increased cMB is associated with greater muscle pathology. We used cMB to
      evaluate the severity of muscle pathology in 55 patients with Duchenne and Becker
      Muscular Dystrophy (D/BMD) compared to 77 controls. cMB was also compared to
      measurements of strength and function. cMB in DMD and BMD increased linearly with
      age and was higher than in controls when groups are compared. cMB increased twice
      as fast with age in DMD than in BMD. In DMD, cMB was higher with reduced function
      and strength. Ultrasound measurement of muscle pathology using cMB is a sensitive
      and objective quantitative technique for determining the severity of muscle
      pathology in dystrophinopathies. Longitudinal studies are required to determine
      the sensitivity of this measure to changes in pathology over time.

PMID- 20817455
TI  - Personalized exon skipping strategies to address clustered non-deletion
      dystrophin mutations.
AB  - Antisense oligomer induced exon skipping is showing promise as a therapy to
      reduce the severity of Duchenne muscular dystrophy. To date, the focus has been
      on excluding single exons flanking frame-shifting deletions in the dystrophin
      gene. However, a third of all Duchenne muscular dystrophy causing mutations are
      more subtle DNA changes. Thirty nine dystrophin exons are potentially frame
      shifting and mutations in these will require the targeted removal of exon blocks
      to generate in-frame transcripts. We report that clustered non-deletion mutations
      in the dystrophin gene respond differently to different antisense oligomer
      preparations targeting the same dual exon block, the removal of which bypasses
      the mutation and restores the open reading-frame. The personalized nature of the
      responses to antisense oligomer application presents additional challenges to the
      induction of multi-exon skipping with a single oligomer preparation.

PMID- 20817456
TI  - Sporadic centronuclear myopathy with muscle pseudohypertrophy, neutropenia, and
      necklace fibers due to a DNM2 mutation.
AB  - Dynamin 2 gene (DNM2) mutations result in an autosomal dominant centronuclear
      myopathy (CNM) and a Charcot-Marie-Tooth (CMT) neuropathy. DNM2-CMT but not DNM2
      CNM patients were noted to have neutropenia. We here report a man with
      paravertebral muscles hypertrophy and mild neutropenia. His muscle biopsy was
      typical for CNM with additional "necklace" fibers. Sequencing of DNM2 revealed a
      known heterozygous c.1269C>T (p.Arg369Trp) mutation. Necklace fibers were
      considered as a pathological hallmark of late onset X-linked CNM due to mutations
      in MTM1 but have not been observed in DNM2-CNM. The findings broaden the features
      of DNM2-myopathy.

PMID- 20817457
TI  - Evaluation of commercial dysferlin antibodies on canine, mouse and human skeletal
      muscle.
AB  - Immunostaining of muscle biopsy cryosections is a powerful tool for identifying
      protein deficiencies. For dysferlin, a protein associated with limb-girdle
      muscular dystrophy and Miyoshi myopathy, weak immunostaining of normal muscle has
      been a problem in reliably identifying dysferlin deficiency in human patients or
      dystrophic animals. Here we use skeletal muscle cryosections from dog, mouse and
      human to test several dysferlin antibodies under different conditions of
      fixation, and without fixation. NCL-Hamlet antibody (mouse monoclonal), following
      fixation in acetone/methanol, provided the strongest and most reliable staining
      in sections of human muscle as well as of dog and mouse muscle. Unlike animal
      tissue, unfixed human muscle also gave strong and reliable staining. NCL-Hamlet 2
      gave good staining in all species. Epitomics (rabbit monoclonal) antibody gave
      good staining of all muscles, and did not stain muscle of dysferlin-deficient
      mice. However, it strongly stained muscle sarcolemma of patients with dysferlin
      deficiency, making the antibody less useful. Abcam antibody gave weak staining,
      and Santa Cruz antibodies did not immunostain muscle dysferlin in any species
      tested. NCL-Hamlet antibody was optimal for immunoblotting in all species. Use of
      select antibodies for immunostaining and immunoblotting, and optimization of
      immunostaining methods, should increase the sensitivity of detecting dysferlin
      deficiency in skeletal muscle.

PMID- 20817458
TI  - Aorto-left renal vein fistula is a rare complication of abdominal aortic aneurysm
      with unique clinical presentation.
AB  - Spontaneous aorto-left renal vein fistulas (ALRVF) are extremely rare, with only
      30 cases presented in the literature. In the majority of the reported cases, the
      fistula involved an anomalous retroaortic left renal vein. In some aspects, the
      clinical findings differ from those of aortocaval fistulas, often making the
      correct diagnosis difficult and contributing to the delay in treatment. In this
      article, we present 2 such cases, review previously reported data, and discuss
      clinical features and treatment options of this rare condition.

PMID- 20817459
TI  - Compression assisted by removable coils as a new treatment for iatrogenic femoral
      pseudoaneurysms.
AB  - To avoid undesirable effects that sometimes result from current treatments for
      postpuncture femoral pseudoaneurysms, we developed a new technique involving
      compression assisted by removable coils. Using ultrasound-guided percutaneous
      puncture, an Inconel coil with synthetic microfibers is inserted in the
      pseudoaneurysm, leaving a part of the coil above the skin. Short-duration,
      ultrasound-guided compression is applied, taking advantage of the coil's
      thrombogenicity. Following occlusion, the coil is removed, leaving no residual
      foreign material. The technique was effective in the first patient treated and
      may minimize or obviate the adverse effects associated with current approaches.

PMID- 20817460
TI  - Diverse evolutionary paths to cell adhesion.
AB  - The morphological diversity of animals, fungi, plants, and other multicellular
      organisms stems from the fact that each lineage acquired multicellularity
      independently. A prerequisite for each origin of multicellularity was the
      evolution of mechanisms for stable cell-cell adhesion or attachment. Recent
      advances in comparative genomics and phylogenetics provide critical insights into
      the evolutionary foundations of cell adhesion. Reconstructing the evolution of
      cell junction proteins in animals and their unicellular relatives exemplifies the
      roles of co-option and innovation. Comparative studies of volvocine algae reveal
      specific molecular changes that accompanied the evolution of multicellularity in
      Volvox. Comparisons between animals and Dictyostelium show how commonalities and
      differences in the biology of unicellular ancestors influenced the evolution of
      adhesive mechanisms. Understanding the unicellular ancestry of cell adhesion
      helps illuminate the basic cell biology of multicellular development in modern
      organisms.

PMID- 20817461
TI  - Extracellular ATP signaling in plants.
AB  - Extracellular adenosine-5'-triphosphate (ATP) induces a number of cellular
      responses in plants and animals. Some of the molecular components for purinergic
      signaling in animal cells appear to be lacking in plant cells, although some
      cellular responses are similar in both systems [e.g. increased levels of
      cytosolic free calcium, nitric oxide (NO), and reactive oxygen species (ROS)].
      The purpose of this review is to compare and contrast purinergic signaling
      mechanisms in animal and plant cells. This comparison will aid our overall
      understanding of plant physiology and also provide details of the general
      fundamentals of extracellular ATP signaling in eukaryotes.

PMID- 20817462
TI  - Impact of serum tumor marker determination on the management of women with
      borderline ovarian tumors: multivariate analysis of a French multicentre study.
AB  - OBJECTIVE: To evaluate the contribution of preoperative serum tumor markers to
      manage borderline ovarian tumors (BOT). STUDY DESIGN: Retrospective multicentre
      study including 317 BOT. Serum tumor marker levels of CA125, CA19-9, CEA, and
      CA15-3 were determined by radio-immunoassay. RESULTS: Among 181 women with serous
      BOT and 136 women with mucinous BOT, respectively 55 of 114 (48.2%) and 38 of 91
      (41.8%) had at least one abnormal value. Women with preoperative tumor marker
      assays were more likely to have radical treatment (p=0.0001), full staging
      (p=0.004), and intra-operative histology (p<0.0001). Women with at least one
      abnormal tumor marker were more likely to undergo laparotomy (p=0.007), to have
      intra-operative histology (p=0.04) and complete staging (p=0.0008). In
      multivariate analysis, first-line laparoscopy was associated with abnormal tumor
      marker levels (OR=9.63; 95%CI=1.40-66.39; p=0.02), while laparotomy was
      associated with large tumors, bilateral tumors, and ascitis visible on
      sonography. CONCLUSION: Serum tumor marker assays modified both preoperative
      assessment and surgical management of BOT.

PMID- 20817464
TI  - Neuroprotective effects of infliximab in experimental spinal cord ischemic
      injury.
AB  - Reactive oxygen species (ROS) have been implicated in the pathogenesis of spinal
      cord injury after both ischemia-reperfusion (I/R) and trauma. This experimental
      study was designed to investigate the potential effects of infliximab, an anti
      tumor necrosis factor-alpha agent, on I/R injury of the rabbit spinal cord.
      Eighteen New Zealand white rabbits were divided into three groups, each
      consisting of six rabbits: sham (no I/R), I/R, and infliximab (I/R + infliximab).
      Spinal cord ischemia was induced by applying an infrarenal aortic cross clamp for
      30 minutes. At 48 hours after ischemia, animals were functionally evaluated using
      the Tarlov score. Changes in the spinal cord were observed by measuring tissue
      levels of malondialdehyde (MDA), glutathione (GSH), advanced oxidation protein
      products (AOPP), and superoxide dismutase (SOD) and by evaluating hematoxylin
      eosin-stained sections. At 48 hours after ischemia, the Tarlov scores in the
      infliximab group were higher than those of the I/R group, MDA and AOPP levels in
      the I/R group were significantly higher than those in the sham and infliximab
      groups (p < 0.05), and SOD levels in the infliximab group were significantly
      higher than those in the I/R and sham groups (p < 0.05). The sham group had
      higher GSH levels than the infliximab group; however, the difference was not
      statistically significant (p > 0.05). Histological examination revealed that the
      infliximab group had significantly less vascular proliferation, edema, and neuron
      loss than the I/R group. These results indicate that infliximab may protect the
      spinal cord against injury in a rabbit I/R model.

PMID- 20817465
TI  - Cystic lesion of the ventriculus terminalis in an adult.
AB  - We present a 40-year-old man with conus medullaris syndrome secondary to a cystic
      lesion of the ventriculus terminalis (CLVT) and review the relevant literature.
      The patient presented with 4 years of worsening right leg weakness, and
      examination showed bilateral fasciculations and hyporeflexia. MRI showed a cystic
      lesion at T11-12. He was managed with a T11-12 laminectomy and fenestration of an
      intramedullary cyst. A total of 32 patients, including ours, have been described
      since 1968: 24 were female with a mean age of 46.6 years. All patients presented
      symptomatically: five were managed conservatively, four using percutaneous
      aspiration under MRI guidance, and 22 with open surgery. We conclude that
      symptomatic patients are best managed surgically, although percutaneous
      aspiration is an emerging technique.

PMID- 20817466
TI  - Primary malignant ganglioglioma of the dorsolumbar spine (D11-L1).
AB  - We report an unusual patient with a primary malignant ganglioglioma, World Health
      Organization (WHO) grade III, of the spinal cord at the D11-L1 level in an 11
      year-old boy. The patient presented with low backache and progressive
      paraparesis. A MRI scan revealed a well-defined conus lesion extending from D11
      to L1, which was predominantly isointense on T1- and T2-weighted images and
      enhanced with contrast. On histopathological evaluation, the tumor was found to
      be comprised of two different components. One of the components revealed typical
      ganglioglioma with dysmorphic ganglion cells, positive for synaptophysin on
      immunohistochemistry. The other component was cellular with a high mitotic
      activity, giant tumor cells and glial fibrillary acidic protein (GFAP)
      positivity. The MIB-1 labeling index was >= 75% in the latter component. We
      emphasize the role of the MIB-1 labeling index to predict the prognosis and
      further management in these rare occurrences.

PMID- 20817467
TI  - The missing button sign as a tool for detecting proximal internal carotid artery
      occlusion.
AB  - The aim of this study was to develop a simple and reliable sign for detecting
      proximal internal carotid artery occlusion (ICAO) using conventional CT scanning.
      The missing button sign (MBS) is defined as the absence of the ICA at the level
      of the foramen magnum on contrast-enhanced CT (CECT) scans. Two raters
      independently reviewed random CECT samples from consecutive patients with acute
      ischaemic stroke. A total of 399 patients with 798 carotid arteries were
      analysed. Rater A identified the MBS in 41 (5%) of the carotid arteries, and did
      not identify the MBS in 735 (92%) carotid arteries. Rater B identified the MBS in
      45 (6%) of the arteries, and lack of the MBS in 731 (91%) arteries. The kappa
      value for agreement was 0.90 (95% CI 0.84-0.95). Compared with CT angiography,
      Rater A's sensitivity, specificity, positive predictive value, and negative
      predictive value for detecting proximal ICAO were 85%, 100%, 100%, and 99%,
      respectively, while Rater B's values were 87%, 99%, 93%, and 99%, respectively.
      This study indicated that the MBS on CECT scanning is both a consistent and
      specific tool for the early identification of proximal ICAO.

PMID- 20817468
TI  - Congenital paraspinal Ewing sarcoma family of tumors with an epidural extension.
AB  - Congenital Ewing sarcoma family of tumors (ESFT) is a rare disease, and only 12
      patients have been reported. Among those patients, only two had paraspinal tumors
      with an epidural extension. A 3-week-old infant boy presented with a huge dorsal
      mass. Whole-spine MRI scans showed a paraspinal mass with an epidural extension
      from the T11 to L2 levels, causing severe spinal cord compression. An initial
      operation was performed to confirm the pathological diagnosis. Twenty days after
      the first operation, the patient showed left lower-extremity weakness. A second
      operation was performed with a laminectomy from the T11 to L2 levels, and the
      epidural mass was radically resected. Pathologically, the tumor was confirmed as
      an ESFT. The patient received adjuvant chemotherapy. His neurological deficit
      recovered after the second surgery, and there was no tumor recurrence during 17
      months of follow-up.

PMID- 20817469
TI  - Microsurgical supraorbital keyhole approach to the anterior cranial base.
AB  - We evaluated treatment of patients with anterior cranial base lesions with
      supraorbital keyhole surgery. Limited supraorbital craniotomy through an eyebrow
      skin incision was performed on 21 adult patients between August 2007 and January
      2009 at one institution. Each patient's cosmesis was evaluated after the
      operation using a visual analog scale for cosmesis (VASC). Thirteen patients were
      treated for ruptured intracranial aneurysms and eight patients for mass lesions
      in the anterior cranial fossa. The mean follow-up duration was 16.5 months. No
      identifiable neurological or vascular complications related to this procedure
      were noted during follow-up; however, two patients died from causes unrelated to
      the procedure. Of the 19 patients who were followed-up, 89% of patients, and 84%
      by physician evaluation, were satisfied with the cosmetic result, noting > 75 mm
      on the VASC. Anterior cranial fossa lesions can be adequately and safely treated
      via a minimally invasive supraorbital craniotomy when performed on suitable
      patients by an experienced surgeon. This approach decreases brain manipulation
      and results in a pleasing cosmetic outcome while minimizing the likelihood of
      procedure-related morbidity.

PMID- 20817470
TI  - The parahippocampal gyrus as a multimodal association area in psychosis.
AB  - Temporal lobe lesions may lead to schizophrenia-like psychosis, a phenomenon
      resembling psychotic disorders such as schizophrenia. We discuss a patient with a
      temporo-basal low-grade glioma presenting with bimodal hallucinosis (visual and
      auditory), a symptom set that is rarely described in psychotic disorders
      associated with morphological correlates. In light of a literature review of
      patients experiencing similar bimodal psychotic symptoms and electrophysiological
      data obtained in non-human primates, we suggest the parahippocampal gyrus to be a
      multimodal association area with bimodal units.

PMID- 20817471
TI  - A retrospective pilot study of African-American and caucasian nursing home
      residents with dementia who died from cancer.

PMID- 20817472
TI  - The importance to including objective functional outcomes in the clinical follow
      up of total knee arthroplasty patients.
AB  - In clinical practice, it is increasingly important to assess patients' daily
      functionality routinely and objectively. Acceleration-based gait analysis (AGA)
      has shown to be reliable and technically suitable for routine clinical use
      outside the laboratory. This study investigated the suitability of AGA for
      measuring function in orthopaedic patients with symptomatic gonarthrosis listed
      for total knee arthroplasty (TKA) by investigating (a) the ability of AGA to
      distinguish patients from healthy subjects, (b) the sensitivity to gait changes
      of AGA in assessing recovery following total knee arthroplasty in a
      subpopulation, and (c) correlations between AGA parameters and clinical scales.
      Gait was assessed using AGA in 24 patients with symptomatic gonarthrosis listed
      for TKA, and in 24 healthy subjects. AGA parameters (e.g. speed, asymmetry) and
      clinical scales (e.g. KSS) were used to monitor progress in 12 patients 3 months
      after TKA. The Mann-Whitney-U test, Receiver Operating Characteristic (ROC)
      curves, repeated measurement ANOVA and Pearson correlations were performed. AGA
      differentiated pathological from healthy gait. The area under the ROC curve,
      sensitivity and specificity values were high for speed, step frequency and step
      length. Different recovery profiles were found, with clinical scales showing
      faster recovery rates. None or only weak correlations were found between AGA and
      clinical scores. AGA was found to be of clinical relevance in identifying and
      monitoring patients with symptomatic gonarthrosis in orthopaedic practice,
      providing objective and additional information about function beyond clinical
      scales. This, together with the fact that AGA can be applied routinely, suggests
      the suitability of AGA for use in rehabilitation programs.

PMID- 20817473
TI  - Thieno[3,2-c]pyrazoles: a novel class of Aurora inhibitors with favorable
      antitumor activity.
AB  - A novel series of 3-amino-1H-thieno[3,2-c]pyrazole derivatives demonstrating high
      potency in inhibiting Aurora kinases was developed. Here we describe the
      synthesis and a preliminary structure-activity relationship, which led to the
      discovery of a representative compound (38), which showed low nanomolar
      inhibitory activity in the anti-proliferation assay and was able to block the
      cell cycle in HCT-116 cell line. This compound demonstrated favorable
      pharmacokinetic properties and good efficacy in the HL-60 xenograft tumor model.

PMID- 20817474
TI  - Acoustic and long-term average spectrum measures to detect vocal aging in women.
AB  - Along the normal aging process, voice tends to become weak, breathy, and loses
      projection, which may interfere in the communication process. One reliable way to
      evaluate voice quality is through acoustical analysis using, for instance, the
      long-term average spectrum (LTAS). The aim of this study was to identify acoustic
      measures, particularly LTAS's, which characterize vocal aging in women without
      vocal complaints. For this purpose, 30 elderly and 30 young women were included
      in this study. All spoke standard Portuguese and none had a history of vocal and
      laryngeal alterations or respiratory diseases. On the basis of the reading task,
      in habitual and loud levels, the following parameters were assessed: the
      equivalent sound level (L(eq)), the speaking fundamental frequency (SFF) and, at
      the LTAS window, the difference between the levels of the regions of the first
      formant and fundamental frequency F(0) (L(1) - L(0)), alpha ratio, and the
      amplitude levels obtained at equal intervals of 160 Hz, ranging from 0 to 8 kHz.
      There were significant differences between young and old voices for SFF and L(eq)
      in both levels. In the LTAS window, amplitude levels were higher for young
      voices, comprising all frequencies except those in the regions between 4.6-6.7
      and 4.8-6.5 kHz, in habitual and loud levels, respectively. There were also
      significant differences regarding L(1) - L(0) and alpha ratio between groups, in
      both levels.The observed differences in LTAS's slopes, L(1) - L(0) measures, and
      even L(eq) and SFF measures, may be attributed, to some extent, to lower
      subglottal pressure or a glottal setting providing a slower glottal closing speed
      for the elderly group.

PMID- 20817475
TI  - Phonation threshold power in ex vivo laryngeal models.
AB  - This study hypothesized that phonation threshold power is measureable and
      sensitive to changes in the biomechanical properties of the vocal folds.
      Phonation threshold power was measured in three sample populations of 10 excised
      canine larynges treated with variable posterior glottal gap, variable bilateral
      vocal fold elongation, and variable vocal fold lesioning. Posterior glottal gap
      varied from 0 to 4mm in 0.5 mm intervals. Bilateral vocal fold elongation varied
      from 0% to 20% in 5% intervals. Vocal fold lesion treatments included unilateral
      and bilateral vocal fold lesion groups. Each treatment was investigated
      independently in a sample population of 10 excised canine larynges. Linear
      regression analysis indicated that phonation threshold power was sensitive to
      posterior glottal gap (R2=0.298, P<0.001) and weakly to vocal fold elongation
      (R2=0.052, P=0.003). A one-way repeated measures analysis of variance indicated
      that phonation threshold power was sensitive to the presence of lesions
      (P<0.001). Theoretical and experimental evidence presented here suggests that
      phonation threshold power could be used as a broad screening parameter sensitive
      to certain changes in the biomechanical properties of the larynx. It has not yet
      been measured in humans, but because it has the potential to represent the
      airflow-tissue energy transfer more completely than the phonation threshold
      pressure or flow alone, it may be a more useful parameter than these and could be
      used to indicate that laryngeal health is likely abnormal.

PMID- 20817476
TI  - A new method for determining the efficiency of large-area beta sources
      constructed from anodized aluminum foils.
AB  - A new method has been developed for determining the efficiency of large-area beta
      sources in anodized aluminum foils using transmission measurements. The method
      was applied to the efficiency measurement of a (90)Sr-(90)Y large-area reference
      source. Measurement results show that the method can provide efficiency values
      for (90)Sr-(90)Y reference sources with standard uncertainties smaller than 2.9%,
      which are far below the limit of 10% required by ISO 8769.

PMID- 20817477
TI  - How do children learn to follow gaze, share joint attention, imitate their
      teachers, and use tools during social interactions?
AB  - How does an infant learn through visual experience to imitate actions of adult
      teachers, despite the fact that the infant and adult view one another and the
      world from different perspectives? To accomplish this, an infant needs to learn
      how to share joint attention with adult teachers and to follow their gaze towards
      valued goal objects. The infant also needs to be capable of view-invariant object
      learning and recognition whereby it can carry out goal-directed behaviors, such
      as the use of tools, using different object views than the ones that its teachers
      use. Such capabilities are often attributed to "mirror neurons". This attribution
      does not, however, explain the brain processes whereby these competences arise.
      This article describes the CRIB (Circular Reactions for Imitative Behavior)
      neural model of how the brain achieves these goals through inter-personal
      circular reactions. Inter-personal circular reactions generalize the intra
      personal circular reactions of Piaget, which clarify how infants learn from their
      own babbled arm movements and reactive eye movements how to carry out volitional
      reaches, with or without tools, towards valued goal objects. The article proposes
      how intra-personal circular reactions create a foundation for inter-personal
      circular reactions when infants and other learners interact with external
      teachers in space. Both types of circular reactions involve learned coordinate
      transformations between body-centered arm movement commands and retinotopic
      visual feedback, and coordination of processes within and between the What and
      Where cortical processing streams. Specific breakdowns of model processes
      generate formal symptoms similar to clinical symptoms of autism.

PMID- 20817479
TI  - A rare case of a glass fragment impacted in the parapharyngeal space associated
      with neurovascular compromise.
AB  - It is rare for foreign bodies to be found in the parapharyngeal space due to the
      protection of the mandibular ramus and zygomatic bone. The authors describe a
      rare case of a patient with an unusual penetrating neck injury caused by broken
      windshield glass in a traffic accident, which lodged in the parapharyngeal space
      and punctured the internal jugular vein and cranial nerves. 3 weeks later, a
      delayed exploration was performed on the patient after detailed evaluation of the
      relationship between the foreign body and the great vessels. The authors removed
      the glass fragment easily with no active bleeding because it had been surrounded
      by a fibrous envelope. This experience indicates that increasing the duration of
      foreign body retention in the parapharyngeal space may be helpful, allowing
      fibrosis to surround the foreign body, reducing the risk of active bleeding when
      it is removed.

PMID- 20817480
TI  - Clinical comparison of patients with osteonecrosis of the jaws, with and without
      a history of bisphosphonates administration.
AB  - This retrospective study aimed to evaluate the role of bisphosphonates in jaw
      osteomyelitis. 29 patients were included: 18 had been treated with
      bisphosphonates (12 with multiple myelomas, 3 with breast carcinomas, 2 with
      prostate carcinomas, and 1 with osteoporosis). Of 11 control patients, 2 had
      breast carcinomas, 2 had bronchial carcinomas, and 7 had no cancer. Descriptive
      and statistical evaluations were conducted to investigate the influence of
      chemotherapy, corticosteroids, stem cell transplantation, and bisphosphonates on
      the development and clinical picture of osteomyelitis. Both groups had similar
      disease histories, clinical pictures, treatment methods, and outcome. Wound
      dehiscence frequencies were also similar (Mann-Whitney rank sum test 1.66+/-1.5
      vs. 1.45+/-2.0 p=0.393). Chemotherapy, steroid therapy, stem cell
      transplantation, or bisphosphonate administration did not correlate with the
      clinical picture. Neither the duration of therapy nor the type of bisphosphonate
      influenced the clinical picture (negative Fisher's tests). The bisphosphonate
      group showed a characteristic settlement of Actinomyces in the exposed bone
      (positive Fisher's test, p=0.021). These results suggested that osteomyelitis
      developed as a consequence of the simultaneous, cumulative action of many
      factors. Bisphosphonates played a role comparable to other predisposing features.
      Coating the jaws with bisphosphonates could promote the settlement of
      Actinomyces.

PMID- 20817481
TI  - Errors in orthognathic surgery planning: the effect of inaccurate study model
      orientation.
AB  - The results of orthognathic surgery may differ significantly from the planned
      outcome using dental models. The orientation of dental models mounted on
      articulators using conventional face bows does not accurately replicate the
      orientation of the patients' teeth and jaws, but introduces a systematic error. A
      mathematical analysis showed that the misalignment of the maxillary model
      introduces errors in the perioperative wafers, which may lead to the incorrect
      surgical positioning of the maxilla reported in the literature. The results of
      the mathematical analysis were validated by image analysis of photographs of
      mounted maxillary models, used to simulate five orthognathic procedures. No
      significant difference between the experimental results and the theoretical
      predictions from the mathematical equations was noted. Planning for maxillary
      forward and upward movement produced more advancement and only 50% of maxillary
      impaction. Planning for maxillary forward and downward movement produced less
      advancement and more inferior displacement in relation to horizontal and vertical
      reference planes.

PMID- 20817482
TI  - Measuring bacterial growth by refractive index tapered fiber optic biosensor.
AB  - A single-mode tapered fiber optic biosensor was utilized for real-time monitoring
      of the Escherichia coli (E. coli K-12) growth in an aqueous medium. The applied
      fiber tapers were fabricated using heat-pulling method with waist diameter and
      length of 6-7MUm and 3mm, respectively. The bacteria were immobilized on the
      tapered surface using Poly-l-Lysine. By providing the proper condition, bacterial
      population growth on the tapered surface increases the average surface density of
      the cells and consequently the refractive index (RI) of the tapered region would
      increase. The adsorption of the cells on the tapered fiber leads to changes in
      the optical characteristics of the taper. This affects the evanescent field
      leading to changes in optical throughput. The bacterial growth rate was monitored
      at room temperature by transmission of a 1558.17nm distributed feedback (DFB)
      laser through the tapered fiber. At the same condition, after determining the
      growth rate of E. coli by means of colony counting method, we compared the
      results with that obtained from the fiber sensor measurements. This novel sensing
      method, promises new application such as rapid analysis of the presence of
      bacteria.

PMID- 20817483
TI  - Safety and proof of principle study of cerebellar vermal theta burst stimulation
      in refractory schizophrenia.
AB  - BACKGROUND: Early invasive electrical stimulation studies suggested that
      enhancement of cerebellar vermal activity might prove valuable in symptomatic
      treatment of refractory neuropsychiatric diseases via modulation of emotion and
      affect. This proof of principle study aimed to test this hypothesis using
      noninvasive brain stimulation, and to explore the safety of this protocol in
      schizophrenia. METHODS: Eight treatment-refractory patients with schizophrenia
      underwent ten sessions of intermittent theta burst stimulation (TBS) to the
      cerebellar vermis using MRI-guided transcranial magnetic stimulation (TMS).
      Assessments included side effect questionnaires, cardiovascular monitoring,
      psychiatric evaluations and comprehensive neuropsychological testing before and
      after TBS and at one-week follow-up. RESULTS: Overall, TBS was tolerated well
      with mild side effects primarily comprising neck pain and headache. No serious
      adverse events occurred. Diastolic blood pressure (BP) showed mild decreases for
      five minutes post-TBS; no significant changes were detected for systolic BP or
      pulse. PANSS negative subscale showed significant improvements following TBS and
      during the follow-up. Calgary Depression Scale and self-report visual analog
      scales for Happiness and Sadness pointed to significant mood elevation.
      Neuropsychological testing revealed significantly fewer omissions in working
      memory and interference conditions of a Continuous Performance Test, a longer
      spatial span and better delay organization on the Rey-Osterrieth Complex Figure
      during follow-up. No significant worsening in psychiatric or neuropsychological
      measures was detected. CONCLUSIONS: Theta burst stimulation of the cerebellar
      vermis is safe and well-tolerated, while offering the potential to modulate
      affect, emotion and cognition in schizophrenia. Future randomized, sham
      stimulation controlled studies are warranted to support the clinical efficacy of
      this technique.

PMID- 20817484
TI  - A pilot investigation of the Graduated Recovery Intervention Program (GRIP) for
      first episode psychosis.
AB  - The Graduated Recovery Intervention Program (GRIP) is a new individual cognitive
      behavioral therapy program designed to facilitate functional recovery in people
      who have experienced an initial episode of psychosis. The purposes of this study
      were to evaluate the feasibility and tolerability of the GRIP intervention, and
      to compare the effectiveness of GRIP versus treatment as usual (TAU) for
      improving specific clinical and psychosocial outcomes. Forty-six individuals with
      first episode psychosis were randomized to GRIP+TAU or TAU alone. Primary
      outcomes focused on social and role functioning, and quality of life. Secondary
      outcomes included psychotic symptoms, depression, substance use, social support,
      attitudes toward medications, well-being, and hospitalizations. The results
      indicate that GRIP was well-tolerated, as evidenced by good attendance and low
      drop-out rates, and well-received (based on positive feedback from participants).
      Although the majority of mixed model analyses were not statistically significant,
      examination of within-group changes and effect sizes suggests an advantage for
      GRIP over TAU in improving functional outcomes. These advantages and the fact
      that the GRIP intervention demonstrated feasibility and tolerability suggest that
      this intervention is worthy of further investigation.

PMID- 20817485
TI  - Increased temporal variability of auditory event-related potentials in
      schizophrenia and Schizotypal Personality Disorder.
AB  - Previous studies suggest that deficits in neural synchronization and temporal
      integration are characteristic of schizophrenia. These phenomena have been rarely
      studied in SPD, which shares phenomenological and genetic similarities with
      schizophrenia. Event-related potentials (ERPs) were obtained using an auditory
      oddball task from 21 patients with schizophrenia, 19 subjects with SPD and 19
      healthy control subjects. Inter-trial coherence (ITC) and event-related spectral
      perturbation (ERSP) were measured across trials to target tones using time
      frequency analysis. ITC measures phase locking or consistency, while ERSP
      measures changes in power relative to baseline activity. P300 latency and
      amplitude were also measured from the averaged ERP to target tones. In the time
      frequency analysis, subjects with SPD showed intact power but a deficit in the
      ITC in delta and theta frequencies compared to control subjects. Patients with
      schizophrenia showed deficits for both ERSP and ITC in the delta and theta
      frequencies. While patients with schizophrenia showed reduced P300 amplitude and
      delayed latency for averaged ERPs, subjects with SPD did not differ from either
      group. Synchronization or timing abnormalities may represent a biomarker for
      schizophrenia spectrum disorders, and contribute to aberrant perceptual and
      cognitive integration.

PMID- 20817486
TI  - Chemerin: at the crossroads of inflammation and obesity.
AB  - Chemerin is a secreted protein with a complex but well-established role in immune
      function. Parallel lines of investigation also support the notion that chemerin
      is a novel adipokine that regulates adipocyte development and metabolic function
      as well as glucose metabolism in liver and skeletal muscle tissues. A growing
      body of human experimental data indicates that serum chemerin levels are elevated
      in patients with obesity and that they exhibit a positive correlation with
      various aspects of the metabolic syndrome. Thus, the dual role of chemerin in
      inflammation and metabolism might provide a link between chronic inflammation and
      obesity, as well as obesity-related disorders such as type 2 diabetes and
      cardiovascular disease.

PMID- 20817487
TI  - Volume reduction of the corpus callosum and its relationship with deficits in
      interhemispheric transfer of information in recent-onset psychosis.
AB  - The present study aimed to investigate the presence of corpus callosum (CC)
      volume deficits in a population-based recent-onset psychosis (ROP) sample, and
      whether CC volume relates to interhemispheric communication deficits. For this
      purpose, we used voxel-based morphometry comparisons of magnetic resonance
      imaging data between ROP (n =122) and healthy control (n = 94) subjects.
      Subgroups (38 ROP and 39 controls) were investigated for correlations between CC
      volumes and performance on the Crossed Finger Localization Test (CFLT).
      Significant CC volume reductions in ROP subjects versus controls emerged after
      excluding substance misuse and non-right-handedness. CC reductions retained
      significance in the schizophrenia subgroup but not in affective psychoses
      subjects. There were significant positive correlations between CC volumes and
      CFLT scores in ROP subjects, specifically in subtasks involving interhemispheric
      communication. From these results, we can conclude that CC volume reductions are
      present in association with ROP. The relationship between such deficits and CFLT
      performance suggests that interhemispheric communication impairments are directly
      linked to CC abnormalities in ROP.

PMID- 20817488
TI  - Reduced right posterior hippocampal volume in women with recurrent familial pure
      depressive disorder.
AB  - Volumetric changes in mood-relevant distributed limbic/paralimbic structures have
      been reported in the recent literature on the course of mood disorders. Patients
      with unipolar and bipolar disorders have been found to have smaller hippocampal
      and anterior cingulate volumes. We examined hippocampal, amygdalar and anterior
      cingulate cortex (ACC) volumes in female patients with recurrent familial pure
      depressive disorder (rFPDD). We used semi-automated software for magnetic
      resonance imaging (MRI) to measure the volumes of the hippocampus, amygdala, ACC
      and subgenual prefrontal cortex (SGPFC) in 15 female patients with familial
      recurrent major depression (MD) and 15 healthy female subjects. Analysis of
      covariance, with whole brain volume as covariate, was used to compare volumetric
      measurements in the two groups. Volumes of the right hippocampal body and tail
      were significantly smaller in female patients with familial depressive disorder
      than in healthy subjects. Our data provide evidence of structural lateralized
      hippocampal body and tail abnormalities in women with familial history and
      recurrent episodes of depression. Although global reduction of hippocampal volume
      has been widely reported, data on lateralized regional reductions in familial
      recurrent depression had not been previously reported. Reduced volume of the
      right posterior hippocampus could be a structural endophenotype for recurrent
      depressive disorders in women.

PMID- 20817489
TI  - Domain III peptides from flavivirus envelope protein are useful antigens for
      serologic diagnosis and targets for immunization.
AB  - The Flavivirus genus of the Flaviviridae family includes 70 enveloped single
      stranded-RNA positive-sense viruses transmitted by arthropods. Among these
      viruses, there are a relevant number of human pathogens including the mosquito
      borne dengue virus (DENV), yellow fever virus (YFV), Japanese encephalitis virus
      (JEV) and West Nile virus (WNV), as well as tick-borne viruses such as tick-borne
      encephalitis virus (TBEV), Langat virus (LGTV) and Omsk hemorrhagic fever (OHFV).
      The flavivirus envelope (E) protein is a dominant antigen inducing immunologic
      responses in infected hosts and eliciting virus-neutralizing antibodies. The
      domain III (DIII) of E protein contains a panel of important epitopes that are
      recognized by virus-neutralizing monoclonal antibodies. Peptides of the DIII have
      been used with promising results as antigens for flavivirus serologic diagnosis
      and as targets for immunization against these viruses. We review here some
      important aspects of the molecular structure of the DIII as well as its use as
      antigens for serologic diagnosis and immunization in animal models.

PMID- 20817490
TI  - Surface modification on polyurethanes by using bioactive carboxymethylated fungal
      glucan from Poria cocos.
AB  - In this work, a water-insoluble beta-D-glucan (PCSG), isolated from Poria cocos,
      was carboxymethylated to create a water-soluble derivative named as CP. After
      free amino groups have been introduced, CP was covalently immobilized onto PU
      surface. The hydrophilicity and the concentration of carboxyl group on the
      modified PU surface were determined. The fibrinogen and albumin adsorption to the
      surface, in vitro blood compatibility, and antibacterial activity of the surface
      against Pseudomonas aeruginosa were evaluated. The water contact angle
      measurement indicated that the hydrophilicity of PU surface increased after
      modification. The fibrinogen adsorption of the modified PU surface decreased
      51.5%, compared with control PU. CP immobilization could prolong the blood
      coagulation time was suggested by APTT experiment. Antibacterial activity
      experiments indicated that CP modified surface obviously suppressed the growth of
      P. aeruginosa. Thereby, CP immobilization improves blood compatibility of PU
      surface and introduces special antibacterial bioactivity.

PMID- 20817491
TI  - Assessment of acute toxicity and histopathology of the fungicide captan in
      rainbow trout.
AB  - Acute toxicity of the fungicide, captan, to juvenile rainbow trout was evaluated
      under static-renewal test condition. Actual concentrations of captan ranged from
      0.05 to 1.00 mg/L. The concentrations of captan that killed 50% of the rainbow
      trout (3.11+/-0.8 g) within 24 (24 h; LC(50)), 48, 72 and 96 h were 0.57+/-0.09,
      0.49+/-0.10, 0.44+/-0.11 and 0.38+/-0.13 mg/L (95% confidence limits),
      respectively. None of the unexposed control fish died and the first fish died 6 h
      after exposure to captan (>=0.65 mg/L). Hypertrophy, separation of epithelium
      from lamellae, lamellar fusion, and epithelial cell necrosis were observed on
      captan exposed fish. Gills also had scattered areas of focal lamellar
      hyperplasia. Fish exposed to fungicide had inflammation and necrosis in liver,
      trunk kidney and spleen. In order, the most affected organs were gill, trunk
      kidney and liver.

PMID- 20817492
TI  - The geometric approach to explore the Bactrocera tau complex (Diptera:
      Tephritidae) in Thailand.
AB  - Specimens of the genus Bactrocera were collected from several host plants in
      northern and western Thailand. They were morphologically recognized as Bactrocera
      tau and were subdivided into eleven samples according to host plant, geographic
      origin and time of collection. Twelve landmarks of the right wing were described
      in a total of 264 males and 276 females. An exploratory analysis using kernel
      density estimates was performed on the multivariate morphometric space. Non
      parametric classification highlighted the existence of two non-overlapping
      clusters within both males and females. The clusters were not congruent with
      geography. One cluster (cluster I) contained only one plant, Momordica
      cochinchinensis, the other one (cluster II) contained five different plants
      including M. cochinchinensis. Further morphometric analyses on selected samples
      indicated that the influence of the plants on the shape of the wing could not
      explain satisfactorily the presence of two clusters. Genetic techniques
      identified the presence of B. tau cryptic species C in M. cochinchinensis from
      cluster I, and of B. tau cryptic species A in Coccinia grandis from cluster II.
      Our working hypothesis is that the two clusters identified by geometric
      morphometrics were species A and C, respectively.

PMID- 20817493
TI  - Feeding anatomy, filter-feeding rate, and diet of whale sharks Rhincodon typus
      during surface ram filter feeding off the Yucatan Peninsula, Mexico.
AB  - The feeding anatomy, behavior and diet of the whale shark Rhincodon typus were
      studied off Cabo Catoche, Yucatan Peninsula, Mexico. The filtering apparatus is
      composed of 20 unique filtering pads that completely occlude the pharyngeal
      cavity. A reticulated mesh lies on the proximal surface of the pads, with
      openings averaging 1.2mm in diameter. Superficial to this, a series of primary
      and secondary cartilaginous vanes support the pads and direct the water across
      the primary gill filaments. During surface ram filter feeding, sharks swam at an
      average velocity of 1.1m/s with 85% of the open mouth below the water's surface.
      Sharks on average spent approximately 7.5h/day feeding at the surface on dense
      plankton dominated by sergestids, calanoid copepods, chaetognaths and fish
      larvae. Based on calculated flow speed and underwater mouth area, it was
      estimated that a whale shark of 443 cm total length (TL) filters 326 m(3)/h, and
      a 622 cm TL shark 614 m(3)/h. With an average plankton biomass of 4.5 g/m(3) at
      the feeding site, the two sizes of sharks on average would ingest 1467 and 2763 g
      of plankton per hour, and their daily ration would be approximately 14,931 and
      28,121 kJ, respectively. These values are consistent with independently derived
      feeding rations of captive, growing whale sharks in an aquarium. A feeding
      mechanism utilizing cross-flow filtration of plankton is described, allowing the
      sharks to ingest plankton that is smaller than the mesh while reducing clogging
      of the filtering apparatus.

PMID- 20817494
TI  - Changing HIV clinical knowledge and skill in context: the impact of longitudinal
      training in the Southeast United States.
AB  - In the Southeast United States, HIV care is provided in a context of
      disproportionate HIV prevalence and barriers to care, including rural locales,
      higher proportions of African American and uninsured patients, and inadequate
      health care workforce and infrastructure. The authors describe a regional on-site
      longitudinal training program developed to target multidisciplinary teams
      providing HIV primary care at clinical sites in the region. The effect of this
      training program was evaluated using pre- and 3-month post-program knowledge and
      skills tests, a post-training evaluation questionnaire, and a post-program focus
      group. The authors found desired effects, with increases in knowledge and skills
      and improved capacity of providers to meet patient care needs across all clinical
      sites despite variations in terms of HIV-infected patient loads. However, the
      lack of enabling factors present in clinic environments may attenuate the
      application of new knowledge and skills, underscoring the relevance of teamwork
      training in HIV care settings.

PMID- 20817495
TI  - Living with a purpose.

PMID- 20817498
TI  - Treatment of haemothorax.
AB  - Haemothorax is a problem commonly encountered in medical practice and is most
      frequently related to open or closed chest trauma or to invasive procedures of
      the chest. Spontaneous haemothorax is less common and can have various causes,
      such as the use of anticoagulants, neoplasia, and rupture of pleural adhesions.
      Identification by radiography and thoracentesis is indicated and treatment of the
      underlying trauma should start immediately. After insertion of a large chest
      tube, antibiotic prophylaxis in trauma patients should be administered for 24 h.
      Further treatment depends on the haemodynamic stability of the patient, the
      volume of evacuated blood and the occurrence of persistent blood loss. Surgical
      exploration by VATS or thoracotomy is necessary if >1.500 ml of blood has
      accumulated and/or an ongoing production of >200 ml of blood per hour is
      observed. If the haemorrhage is less severe, careful investigation into the
      underlying cause must be performed and blood should be evacuated by tube
      thoracostomy. If clotted blood retained in spite of tube thoracostomy,
      intrapleural fibrinolytic therapy can be applied to breakdown clots and
      adhesions. If conservative treatment is insufficient, a surgical approach with
      VATS or thoracotomy is indicated to prevent subsequent complications.

PMID- 20817496
TI  - Omega-3 fatty acid deficiency increases constitutive pro-inflammatory cytokine
      production in rats: relationship with central serotonin turnover.
AB  - Omega-3 (n-3) fatty acid deficiency, elevated inflammatory signaling, and central
      serotonin (5-HT) turnover have separately been implicated in the pathophysiology
      of major depressive disorder (MDD). In the present study we investigated the
      interrelationship between n-3 fatty acid status, pro-inflammatory signaling
      activity, and central 5-HT turnover in vivo. Rats were fed diets with or without
      the n-3 fatty acid precursor alpha-linolenic acid (ALA) during perinatal
      development (E0-P100), and a subset of rats fed the ALA- diet were switched to
      the ALA+ diet post-weaning (P21-P100, repletion). In adulthood (P100), plasma
      interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFalpha), and C-reactive
      protein (CRP) levels were measured. Additionally, indices of liver n-6 fatty acid
      biosynthesis, erythrocyte fatty acid composition, and regional brain monoamine
      turnover were determined. Indices of liver delta-6 desaturase activity were up
      regulated in n-3-deficient rats, and were associated with greater erythrocyte
      membrane arachidonic acid (AA, 20:4 n-6) composition. Plasma IL-6 (p=0.001),
      TNFalpha (p=0.02), and CRP (p=0.001) concentrations were significantly greater in
      n-3-deficient rats relative to controls. The 5-HIAA/5-HT ratio was significantly
      greater in frontal cortex, hypothalamus, and ventral striatum of n-3-deficient
      rats relative to controls. Changes in membrane n-3 and n-6 fatty acid
      composition, elevations in plasma IL-6 and TNFalpha, and increased central 5-HT
      turnover were all prevented by normalization of n-3 fatty acid status.
      Erythrocyte docosahexaenoic acid (DHA, 22:6 n-3) was inversely correlated, and AA
      and the AA/DHA and AA/eicosapentaenoic acid ratios were positively correlated,
      with plasma IL-6, TNFalpha, and CRP levels. Plasma IL-6 levels were positively
      correlated with 5-HIAA/5-HT ratios in all brain regions. These preclinical data
      provide evidence for a functional link between n-3 fatty acid deficiency,
      elevated peripheral inflammatory signaling, and increased central 5-HT turnover.

PMID- 20817499
TI  - Microtubule tip-interacting proteins: a view from both ends.
AB  - Microtubule ends serve as sites of tubulin addition and removal, and at the same
      time play crucial roles in microtubule capture, stabilization and attachment to
      different cellular structures. Microtubule plus and minus-ends possess distinct
      structural and dynamic properties, and are recognized, bound and regulated by
      diverse factors. These include specific capping factors such as gamma-tubulin,
      motors, such as plus-end and minus-end directed kinesins, highly specialized
      kinetochore-bound microtubule-associated proteins, and comet-making plus-end
      tracking proteins such as EB1 and its partners. Here, we provide an overview of
      microtubule tip-interacting proteins and the mechanisms responsible for their
      association with microtubule ends, and discuss the functional cross-talk between
      microtubule plus and minus-end binding factors.

PMID- 20817500
TI  - Germline stem cells: stems of the next generation.
AB  - Germline stem cells (GSCs) sustain gametogenesis during the life of organisms.
      Recent progress has substantially extended our understanding of GSC behavior,
      including the mechanisms of stem cell self-renewal, asymmetric stem cell
      division, stem cell niches, dedifferentiation, and tissue aging. GSCs typically
      are highly proliferative, owing to organismal requirement to produce large number
      of differentiated cells. While many somatic stem cells are multipotent, with
      multiple differentiation pathways, GSCs are unipotent. For these relatively
      simple characteristics (e.g. constant proliferation and unipotency), GSCs have
      served as ideal model systems for the study of adult stem cell behavior, leading
      to many important discoveries. Here, we summarize recent progress in GSC biology,
      with an emphasis on evolutionarily conserved mechanisms.

PMID- 20817501
TI  - Planar cell polarity signaling, cilia and polarized ciliary beating.
AB  - Planar cell polarity signaling governs a wide array of polarized cell behaviors
      in animals. Recent reports now show that PCP signaling is essential for the
      directional beating of motile cilia. Interestingly, PCP signaling acts in a
      variety of ciliated cell types that use motile cilia to generate directional
      fluid flow in very different ways. This review will synthesize these recent
      papers and place them in context with previous studies of PCP signaling in
      polarized cellular morphogenesis and collective cell movement.

PMID- 20817502
TI  - Imaging mass spectrometry reveals unique lipid distribution in primary varicose
      veins.
AB  - BACKGROUND: The lipid metabolism of varicose veins (VVs) remains unknown. To
      elucidate the pathogenesis of VV, we utilized the novel technique of imaging mass
      spectrometry (IMS). MATERIALS AND METHODS: We obtained VV tissues from 10 limbs
      of 10 VV patients who underwent great saphenous vein stripping. As control vein
      samples, we harvested segmental vein tissues from 6 limbs of 6 patients with
      peripheral artery occlusive disease who underwent infra-inguinal bypass with
      reversed saphenous vein grafting. To identify the localisation of lipid molecules
      in the VV tissues, we performed matrix-assisted laser desorption/ionization IMS
      (MALDI-IMS). We also performed MS/MS analyses to identify the structure of each
      molecule. RESULTS: We obtained mass spectra directly from control vein tissues
      and VV tissues and found a unique localisation of lipid molecules in the VV
      tissues. We localised lysophosphatidylcholine (LPC) (1-acyl 16:0),
      phosphatidylcholine (PC) (1-acyl 36:4) and sphingomyelin (SM) (d18:1/16:0) at the
      site of the VV valve. CONCLUSION: MALDI-IMS revealed the distribution of various
      lipid molecules in normal veins and VVs both. Accumulation of LPC (1-acyl 16:0),
      PC (1-acyl 36:4) and SM (d18:1/16:0) in the VV tissues suggested that
      inflammation associated with abnormal lipid metabolism may contribute to the
      development of VV.

PMID- 20817503
TI  - Gypsum treated fly ash as a liner for waste disposal facilities.
AB  - Fly ash has potential application in the construction of base liners for waste
      containment facilities. While most of the fly ashes improve in the strength with
      curing, the ranges of permeabilities they attain may often not meet the basic
      requirement of a liner material. An attempt has been made in the present context
      to reduce the hydraulic conductivity by adding lime content up to 10% to two
      selected samples of class F fly ashes. The use of gypsum, which is known to
      accelerate the unconfined compressive strength by increasing the lime reactivity,
      has been investigated in further improving the hydraulic conductivity. Hydraulic
      conductivities of the compacted specimens have been determined in the laboratory
      using the falling head method. It has been observed that the addition of gypsum
      reduces the hydraulic conductivity of the lime treated fly ashes. The reduction
      in the hydraulic conductivity of the samples containing gypsum is significantly
      more for samples with high amounts of lime contents (as high as 1000 times) than
      those fly ashes with lower amounts of lime. However there is a relatively more
      increase in the strengths of the samples with the inclusion of gypsum to the fly
      ashes at lower lime contents. This is due to the fact that excess lime added to
      fly ash is not effectively converted into pozzolanic compounds. Even the presence
      of gypsum is observed not to activate these reactions with excess lime. On the
      other hand the higher amount of lime in the presence of sulphate is observed to
      produce more cementitious compounds which block the pores in the fly ash. The
      consequent reduction in the hydraulic conductivity of fly ash would be beneficial
      in reducing the leachability of trace elements present in the fly ash when used
      as a base liner.

PMID- 20817504
TI  - Direct electrochemistry and electrocatalysis of myoglobin covalently immobilized
      in mesopores cellular foams.
AB  - Myoglobin (Mb) was firstly covalently immobilized into mesopores cellular foams
      (MCFs) to fabricate the protein electrode (Mb-MCFs/GC electrode) and study the
      direct electrochemistry of redox protein. The results of UV-vis and FTIR spectra
      illustrated that the covalently immobilized Mb well retained its native structure
      and presented good stability. Cyclic voltammetry of Mb-MCFs/GC electrode showed
      nearly reversible cyclic voltammetric peaks, indicating the direct electron
      transfer of Mb-FeIII/FeII. In addition, Mb-MCFs/GC electrode exhibited favorable
      electrocatalytic reduction to H2O2 with high sensitivity, good thermal and long
      time stability. Such an avenue, which integrated mesopores cellular foams and
      redox protein via a simple covalent method, may provide a novel and efficient
      platform for the fabrication of the third generation biosensor.

PMID- 20817505
TI  - The impact of MYC expression in lymphoma biology: beyond Burkitt lymphoma.
AB  - Although classically described as the driving oncogene in Burkitt lymphoma (BL),
      abnormalities of MYC have been recognized in other non-Hodgkin lymphomas as well.
      For example, MYC is overexpressed in approximately 10% of diffuse large B-cell
      lymphomas (DLBCL), conferring an adverse prognosis with chemoresistance and
      shortened survival; only approximately 30% of patients achieve long-term survival
      despite modern therapies. In contrast to BL, MYC aberrations in DLBCL are usually
      associated with multiple cytogenetic abnormalities and other genetic lesions,
      such as concurrent BCL2 translocations. Patients with so-called "double-hit"
      lymphomas have a worse outcome with few survivors beyond 6 months. It is unclear
      why MYC translocations are diagnostic in BL but prognostic in other lymphomas;
      different mechanisms underlying MYC abnormalities and a unique target set of
      genes may explain some of the variance. Furthermore, MYC possesses
      nontranscriptional functions other than transcriptional controls on genes
      regulating cell growth and may also influence the lymphoma microenvironment. Here
      we summarize current knowledge regarding MYC in lymphomas other than Burkitt
      lymphoma, with an emphasis on transcriptional, epigenetic, clinical, and
      microenvironmental consequences.

PMID- 20817506
TI  - Notch protection against apoptosis in T-ALL cells mediated by GIMAP5.
AB  - Recent studies have highlighted the role of Notch signalling in the development
      of T cell acute lymphoblasic leukaemia (T-ALL). Over-expression of Notch3 and
      gain of function mutations in the Notch1 gene have been reported. The aims of
      this study were to determine the effect of Notch signalling on apoptosis in human
      T-ALL cell lines and to identify targets of Notch signalling that may mediate
      this effect. Functional studies showed that inhibition of Notch signalling using
      gamma secretase inhibitors promoted glucocorticoid-induced apoptosis in cells
      carrying gain of function mutations in Notch1. Moreover, ectopic expression of
      constitutively activated Notch provided protection against glucocorticoid-induced
      apoptosis, indicating that signalling via Notch may also contribute to the
      development of T-ALL by conferring resistance to apoptosis. Microarray analysis
      revealed that GIMAP5, a gene coding for an anti-apoptotic intracellular protein,
      is upregulated by Notch in T-ALL cell lines. Knockdown of GIMAP5 expression using
      siRNA promoted glucocorticoid-induced apoptosis in T-ALL cells carrying gain of
      function mutations in Notch1 and in T-ALL cells engineered to express ectopic
      constitutively activated Notch indicating that Notch signalling protects T-ALL
      cells from apoptosis by upregulating the expression of GIMAP5.

PMID- 20817507
TI  - Systems biology of the gut: the interplay of food, microbiota and host at the
      mucosal interface.
AB  - Our intestinal tract is colonized since birth by complex and subject-specific
      microbial communities that interact with the host. The human adult microbiota has
      recently been characterized by deep metagenomic sequencing and several hundreds
      of intestinal genomes have been characterized at the sequence level. Moreover,
      the transcriptional response of the host and selected microbes has been
      identified both in animal model systems and in human. Similarly, the
      transcriptional response of the host to different diets has been determined in
      humans, germ-free and gene knockout animals. These developments bring the
      intestinal tract in the realm of systems biology. An integrated, modular
      modelling framework that cross-links top-down and bottom-up approaches for the
      various levels of biological organization is paramount for the understanding of
      intestinal function.

PMID- 20817508
TI  - Anesthesiologists' practices for late termination of pregnancy: a French national
      survey.
AB  - BACKGROUND: Approximately 6600 cases of medical termination of pregnancy are
      performed in France annually, of which 78% are performed during the second or
      third trimester of pregnancy. There are few data and no recommendations regarding
      anesthesia and analgesia for these late terminations. The aims of this study were
      to determine the role of anesthesiologists and analgesia and anesthesia practices
      used for late terminations in France. METHODS: An electronic mailing survey was
      sent to all obstetric anesthesia teams working in hospitals with a prenatal
      diagnosis center in France. The same survey was also sent to a sample of
      obstetric anesthesia teams working in hospitals near Paris without a prenatal
      diagnosis center. RESULTS: The response rate was 96% (45/47) for those with and
      85% (23/27) for those without a prenatal diagnosis centre. Anesthesiologists at
      units with prenatal diagnosis participate on a regular or frequent basis on
      multidisciplinary prenatal committees in 36% of responding centers and are
      involved in 69% of centers in case of maternal health problems. Epidural or more
      rarely combined spinal-epidural analgesia is performed in more than 90% of cases.
      The block is performed after fetocide in 22% of centers and after the start of
      labor in 38% of centers. Sedation or general anesthesia is used at delivery in
      every case or at patient request in 2% and 60% of centers, respectively. Minor
      differences were found when comparing practices of high-volume centers with
      prenatal diagnosis and small volume centers without. CONCLUSIONS: French
      anesthesiologists do not participate routinely in the decision and planning of
      all late terminations. Overall, very similar analgesic and anesthetic practices
      are observed in high- and low- volume centers, with epidural techniques being the
      most common.

PMID- 20817509
TI  - Gender differences in nightmare frequency: a meta-analysis.
AB  - Many studies have reported gender differences in nightmare frequency. In order to
      study this difference systematically, data from 111 independent studies have been
      included in the meta-analysis reported here. Overall, estimated effect sizes
      regarding the gender difference in nightmare frequency differed significantly
      from zero in three age groups of healthy persons (adolescents, young adults, and
      middle-aged adults), whereas for children and older persons no substantial gender
      difference in nightmare frequency could be demonstrated. There are several
      candidate variables like dream recall frequency, depression, childhood trauma,
      and insomnia which might explain this gender difference because these variables
      are related to nightmare frequency and show stable gender differences themselves.
      Systematic research studying the effect of these variables on the gender
      difference in nightmare frequency, though, is still lacking. In the present study
      it was found that women tend to report nightmares more often than men but this
      gender difference was not found in children and older persons. Starting with
      adolescence, the gender difference narrowed with increasing age. In addition,
      studies with binary coded items showed a markedly smaller effect size for the
      gender difference in nightmare frequency compared to the studies using multiple
      categories in a rating scale. How nightmares were defined did not affect the
      gender difference. In the analyses of all studies and also in the analysis for
      the children alone the data source (children vs. parents) turned out to be the
      most influential variable on the gender difference (reporting, age). Other
      results are also presented. Investigating factors explaining the gender
      difference in nightmare frequency might be helpful in deepening the understanding
      regarding nightmare etiology and possibly gender differences in other mental
      disorders like depression or posttraumatic stress disorder.

PMID- 20817510
TI  - Content comparison of 115 health status measures in sleep medicine using the
      International Classification of Functioning, Disability and Health (ICF) as a
      reference.
AB  - The objective of this systematic review and content analysis was to identify and
      quantify the concepts contained in patient-administered health status measures in
      sleep medicine practice and research using the International Classification of
      Functioning, Disability and Health (ICF) as a reference. Both generic and
      condition-specific patient-administered measures/questionnaires used in sleep
      medicine practice and research were identified and selected. A comprehensive
      search strategy for reviews, National/International Guidelines and Standard
      References to ensure that all areas of functioning, disability and health were
      captured was used. The contents of the selected measures were examined and linked
      to the ICF using established linking rules. The frequencies of ICF categories
      covering the concepts contained in the 115 patient-administered measures were
      used for the descriptive analysis and content comparison. Of these, 35 were of a
      generic nature, 17 were symptom-related, and 63 condition-specific. The concepts
      identified in the questionnaires' items were predominantly linked to categories
      of the ICF component related to body functions (61.4%), followed by activities
      and participation (15.3%), and then environmental factors (9.8%). The measures
      vary greatly with regard to the number and specificity of the ICF categories
      covered, as indicated by the proportional indices of content density and content
      diversity. The ICF provides a useful reference to identify, quantify and compare
      the concepts contained in health status measures used in sleep medicine practice
      and research.

PMID- 20817511
TI  - Homeopathy for insomnia: summary of additional RCT published since systematic
      review.

PMID- 20817512
TI  - Microglia-neuronal signalling in neuropathic pain hypersensitivity 2.0.
AB  - Microglia are increasingly recognized as critical in the pathogenesis of pain
      hypersensitivity caused by injury to peripheral nerves. The core signalling
      pathway is through P2X4 purinergic receptors on the microglia which, via the
      release of brain-derived neurotrophic factor, cause disinhibition of nociceptive
      dorsal horn neurons by raising intracellular chloride levels. This disinhibition
      works in synergy with enhanced excitatory synaptic transmission in the dorsal
      horn to transform the output of the nociceptive network. There is increased
      discharge output, unmasking of responses to innocuous peripheral inputs and
      spontaneous activity in neurons that otherwise only signal nociception. Together
      the changes caused by microglia-neuron signalling may account for the main
      symptoms of neuropathic pain in humans.

PMID- 20817513
TI  - Meta-analysis of the impact of surgical margins on local recurrence in women with
      early-stage invasive breast cancer treated with breast-conserving therapy.
AB  - PURPOSE: There is no consensus on what constitutes adequate negative margins in
      breast-conserving therapy (BCT). We review the evidence on surgical margins in
      BCT for early-stage invasive breast cancer. METHODS: Meta-analysis of studies
      reporting local recurrence (LR) relative to quantified final microscopic margin
      status and the threshold distance for negative margins. The proportion of LR was
      modelled using random effects logistic meta-regression. RESULTS: Based on 21
      studies (LR in 1,026 of 14,571 subjects) the odds of LR were associated with
      margin status [model 1: odds ratio (OR) = 2.02 for positive/close versus
      negative; model 2: OR = 1.80 for close versus negative, 2.42 for positive versus
      negative (P<0.001 both models)] but not with margin distance [1mm versus 2mm
      versus 5mm (P > 0.10 both models)], adjusting for median follow-up time. However,
      there was weak evidence in both models that the odds of LR decreased as the
      threshold distance for declaring negative margins increased. This bordered
      significance in model 2 [OR for 1mm, 2mm, 5mm: 1.0, 0.75, 0.51 (P = 0.097 for
      trend)], and was not significant in model 1 [OR for 1mm, 2mm, 5mm: 1.0, 0.85,
      0.58 (P = 0.11 for trend)] but was evident when one study (of women <= 40 years)
      was excluded from this model [OR for 1mm, 2mm, 5mm: 1.0, 0.72, 0.52 (P = 0.058
      for trend)]: this trend was rendered insignificant by adjustment for the
      proportion of subjects receiving a radiation boost or the proportion of subjects
      receiving endocrine therapy. CONCLUSIONS: Margin status has a prognostic effect
      in all women treated for invasive breast cancer; increasing the threshold
      distance for declaring negative margins is weakly associated with reduced odds of
      LR, however adjustment for covariates (adjuvant therapy) removes the significance
      of this effect. Adoption of wider margins, relative to narrower widths, for
      declaring negative margins is unlikely to a have substantial additional benefit
      for long-term local control in BCT.

PMID- 20817514
TI  - Thermogravimetric analysis of the combustion of microalgae and microalgae blended
      with waste in N2/O2 and CO2/O2 atmospheres.
AB  - The combustion of microalgae and municipal solid waste (MSW) under N2/O2 and
      CO2/O2 atmospheres was analyzed using a thermogravimetric instrument. The onset
      temperature of volatile release (Tv), maximum rate of weight loss (Rmax) and the
      temperature at the maximal peak (Tmax) were measured. As the blending ratio of
      microalgae was increased from 10% to 70% under N2/O2 atmosphere, Tv decreased
      from 269.4 to 247.4  degrees C, Tmax decreased from 310.8 to 288.0  degrees C,
      Rmax decreased from 11.94% to 7.88% and residual weight decreased from 30% to
      20%. Thus, blending with microalgae can improve MSW combustion. The type of
      atmosphere did not affect Tv and Tmax, but replacement of N2 by CO2, resulted in
      the later appearance of the small humps (>600  degrees C) in the mass loss and
      rate of weight loss curves, burnout was less complete, and Rmax was lower, thus
      some improvement measures, such as an increase in oxygen concentration, are
      required under CO2/O2 atmosphere to achieve the same combustion performances in
      air.

PMID- 20817515
TI  - Apoptosis in postweaning multisystemic wasting syndrome (PMWS) hepatitis in pigs
      naturally infected with porcine circovirus type 2 (PCV2).
AB  - The degree of apoptosis in the livers of pigs with hepatitis due to naturally
      occurring postweaning multisystemic wasting syndrome (PMWS) was evaluated semi
      quantitatively by immunohistochemical detection of the apoptotic marker cleaved
      caspase-3 (CCasp3). The amount and distribution of porcine circovirus type 2
      (PCV2) virus in the liver was evaluated using in situ hybridisation. Livers with
      mild, stage I hepatitis exhibited similar degrees of apoptosis to controls; those
      with stage II lesions had variable apoptotic rates, ranging from mild to high,
      and in livers with more severe, stage III hepatitis, high levels of hepatocyte
      apoptosis was a feature. Statistical analyses indicated a positive association
      between the rate of apoptosis, the severity of the hepatitis and the amount of
      PCV2 DNA in the liver. Double immunolabelling for CCasp3 and PCV2 DNA revealed a
      predominance of cells labelling only for PCV2, followed by fewer cells labelling
      only for CCasp3, and the least number labelling for both. The findings suggest
      that apoptosis, possibly triggered by PCV2 infection and/or hepatic inflammation,
      plays a key role in the pathogenesis of hepatitis in pigs with naturally
      occurring PMWS.

PMID- 20817516
TI  - An exon 1 deletion in OTC identified using chromosomal microarray analysis in a
      mother and her two affected deceased newborns: implications for the prenatal
      diagnosis of ornithine transcarbamylase deficiency.
AB  - We describe the outcome of two consecutive pregnancies with a clinical
      presentation of ornithine transcarbamylase (OTC) deficiency (OTCD) without a
      molecular diagnosis. A 119kb deletion on Xp11.4 including the OTC gene was
      detected in the mother. The same deletion was identified in the blood spots from
      deceased male newborns. In patients with a clinical and biochemical presentation
      of OTCD and negative OTC sequencing, whole genome or targeted chromosomal
      microarray analysis (CMA) with coverage of the OTC and neighboring genes should
      be performed as a reflex test.

PMID- 20817518
TI  - Synthesis and in vitro evaluation of N-alkyl-7-methoxytacrine hydrochlorides as
      potential cholinesterase inhibitors in Alzheimer disease.
AB  - All approved drugs for Alzheimer disease (AD) in clinical practice ameliorate the
      symptoms of the disease. Among them, acetylcholinesterase inhibitors (AChEIs) are
      used to increase the cholinergic activity. Among new AChEI, tacrine compounds
      were found to be more toxic compared to 7-MEOTA (9-amino-7-methoxy-1,2,3,4
      tetrahydroacridine). In this Letter, series of 7-MEOTA analogues (N-alkyl-7
      methoxytacrine) were synthesized. Their inhibitory ability was evaluated on
      recombinant human acetylcholinesterase (AChE) and plasmatic human
      butyrylcholinesterase (BChE). Three novel compounds showed promising results
      towards hAChE better to THA or 7-MEOTA. Three compounds resulted as potent
      inhibitors of hBChE. The SAR findings highlighted the C(6)-C(7)N-alkyl chains for
      cholinesterase inhibition.

PMID- 20817517
TI  - Tay-Sachs disease in Jacob sheep.
AB  - Autopsy studies of four Jacob sheep dying within their first 6-8 months of a
      progressive neurodegenerative disorder suggested the presence of a neuronal
      storage disease. Lysosomal enzyme studies of brain and liver from an affected
      animal revealed diminished activity of hexosaminidase A (Hex A) measured with an
      artificial substrate specific for this component of beta-hexosaminidase. Absence
      of Hex A activity was confirmed by cellulose acetate electrophoresis. Brain lipid
      analyses demonstrated the presence of increased concentrations of G(M2)
      ganglioside and asialo-G(M2)-ganglioside. The hexa cDNA of Jacob sheep was cloned
      and sequenced revealing an identical number of nucleotides and exons as in human
      HexA and 86% homology in nucleotide sequence. A missense mutation was found in
      the hexa cDNA of the affected sheep caused by a single nucleotide change at the
      end of exon 11 resulting in skipping of exon 11. Transfection of normal sheep
      hexa cDNA into COS1 cells and human Hex A-deficient cells led to expression of
      Hex S but no increase in Hex A indicating absence of cross-species dimerization
      of sheep Hex alpha-subunit with human Hex beta-subunits. Using restriction site
      analysis, the heterozygote frequency of this mutation in Jacob sheep was
      determined in three geographically separate flocks to average 14%. This large
      naturally occurring animal model of Tay-Sachs disease is the first to offer
      promise as a means for trials of gene therapy applicable to human infants.

PMID- 20817519
TI  - Methylantcinate A induces tumor specific growth inhibition in oral cancer cells
      via Bax-mediated mitochondrial apoptotic pathway.
AB  - An ergostane type triterpenoid methylantcinate A (MAA) isolated from the fruiting
      bodies of Antrodia camphorata inhibited the growth of oral cancer cell lines OEC
      M1 and OC-2 in a dose-dependent manner, without cytotoxic to normal oral gingival
      fibroblast cells. The major mechanism of growth inhibition was apoptosis
      induction, as shown by flow cytometric analysis of annexin V-FITC and propidium
      iodide staining, caspase-3 activation and DNA fragmentation. The increased
      expression of pro-apoptotic Bax, poly-(ADP-ribose) polymerase cleavage, and
      activated caspase-3 and decreased expression of anti-apoptotic Bcl-2 and Bcl-xL
      were also observed. These results provide the first evidence that the anti-oral
      cancer effects of MAA may involve a mechanism through the mitochondrial dependent
      pathway. Thus, results reported here may offer further impulse to the development
      of MAA analogues as potential chemotherapeutic targets for oral cancer
      complications.

PMID- 20817520
TI  - Role of the phenolic hydroxyl group in the biological activities of simplified
      analogue of aplysiatoxin with antiproliferative activity.
AB  - The 18-deoxy derivative (3) of a simplified analogue (1) of aplysiatoxin with
      antiproliferative activity was synthesized to examine the role of the phenolic
      hydroxyl group at position 18 in the biological activities of 1. Compound 3 as
      well as 1 showed significant affinity for protein kinase Cdelta (PKCdelta), and
      the antiproliferative activity of 3 was slightly higher than that of 1. However,
      the anti-tumor-promoting activity of 3 was less than that of 1 in vitro,
      suggesting that the phenolic hydroxyl group of 1 is necessary for the anti-tumor
      promoting activity but not for the binding of PKCdelta and antiproliferative
      activity. Moreover, PKC isozyme selectivity of 3 was similar to that of 1,
      suggesting non-PKC receptors for these compounds to play some roles in the anti
      tumor-promoting activity of 1.

PMID- 20817521
TI  - A novel series of positive modulators of the AMPA receptor: structure-based lead
      optimization.
AB  - Starting from lead compound 1, we demonstrate how X-ray structural data can be
      used to understand SAR and expediently optimize bioavailability in a novel series
      of AMPA receptor modulators, furnishing 5 with improved bioavailability and
      robust in vivo activity.

PMID- 20817524
TI  - A novel 18F-labeled pyridyl benzofuran derivative for imaging of beta-amyloid
      plaques in Alzheimer's brains.
AB  - A potential probe for PET targeting beta-amyloid plaques in Alzheimer's disease
      (AD) brain, FPYBF-1 (5-(5-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)
      N,N-dimethylpyridin-2-amine), was synthesized and evaluated. In experiments in
      vitro, FPYBF-1 displayed high affinity for Abeta(1-42) aggregates (K(i)=0.9 nM),
      and substantial labeling of beta-amyloid plaques in sections of postmortem AD
      brains but not control brains. In experiments in vivo, [(18)F]FPYBF-1 displayed
      good initial uptake (5.16%ID/g at 2 min postinjection) and rapid washout from the
      brain (2.44%ID/g at 60 min postinjection) in normal mice, and excellent binding
      to beta-amyloid plaques in a murine model of AD. Furthermore, the specific
      labeling of plaques labeling was observed in autoradiographs of autopsied AD
      brain sections. [(18)F]FPYBF-1 may be a useful probe for imaging beta-amyloid
      plaques in living brain tissue.

PMID- 20817523
TI  - Substituted 4-amino-1H-pyrazolo[3,4-d]pyrimidines as multi-targeted inhibitors of
      insulin-like growth factor-1 receptor (IGF1R) and members of ErbB-family receptor
      kinases.
AB  - This Letter describes the lead discovery, optimization, and biological
      characterization of a series of substituted 4-amino-1H-pyrazolo[3,4-d]pyrimidines
      as potent inhibitors of IGF1R, EGFR, and ErbB2. The leading compound 11 showed an
      IGF1R IC(50) of 12 nM, an EGFR (L858R) IC(50) of 31 nM, and an ErbB2 IC(50) of 11
      nM, potent activity in cellular functional and anti-proliferation assays, as well
      as activity in an in vivo pharmacodynamic assay.

PMID- 20817525
TI  - CD3+ and BLA.36+ cells do not occur in the epidermis and adnexal epithelia of
      normal skin from the dorsolateral trunk of cats.
AB  - A small population of resident T-lymphocytes is present in the normal epidermis
      of humans, mice, and rats. However, resident epidermal lymphocytes have not been
      reported in the normal skin of the cat. Skin-biopsy specimens from the normal
      skin of the dorsolateral trunk from 30 cats were examined histologically and
      immunohistochemically for the presence of lymphocytes, CD3+ cells, and BLA.36+
      cells in epidermis and adnexal epithelia. All examinations were negative. It
      appears that lymphocytes occur rarely, if at all, in the epidermis and adnexal
      epithelial of normal cat skin. Hence, the presence of lymphocytes in these
      structures should be considered abnormal.

PMID- 20817522
TI  - Fatty acid amide signaling molecules.
AB  - Key studies leading to the discovery and definition of the role of endogenous
      fatty acid amide signaling molecules are summarized.

PMID- 20817526
TI  - Multiple recurrent pancreatic cysts with associated pancreatic inflammation and
      atrophy in a cat.
AB  - Previous reports of true pancreatic cysts in cats have suggested that pancreatic
      cysts in cats are benign incidental findings. This case report describes the
      progressive clinical course and diagnostic findings in a cat with multiple
      recurrent pancreatic cysts. The presenting clinical signs included diarrhea,
      intermittent vomiting, polyphagia, and marked weight loss. Pancreatic cysts were
      identified via abdominal ultrasound and computed tomography (CT). An exploratory
      celiotomy and lesion histopathology confirmed multiple true pancreatic cysts of
      unknown etiology. One month after surgery the cat presented for lethargy and
      decreased appetite. Clinical re-evaluation was diagnostic for diabetes mellitus
      and an abdominal ultrasound confirmed recurrence of the pancreatic cysts. The
      recurrent nature of the pancreatic cysts and the concurrent development of
      diabetes mellitus were suggestive of progressive loss of pancreatic function or
      insulin resistance. This is the first described case of multiple recurring
      pancreatic cysts in a cat associated with pancreatic inflammation, atrophy and
      endocrine dysfunction.

PMID- 20817527
TI  - A series of six cases of sphincter of Oddi pathology in the cat (2008-2009).
AB  - The sphincter of Oddi (SO) is located within the wall of the duodenum as the
      terminal part of the common bile duct. Six cats are reported with obstructive
      processes within their SO. Three of them may have had some form of sphincter
      dysfunction associated with the pre-existing complex known as 'inflammatory bowel
      disease' (IBD), two may have had the equivalent of the infant human condition
      known as 'bile plug syndrome' and the sixth had sphincter dysfunction associated
      with a tumour at the confluence of the common and right hepatic duct. In all six
      cases, the sphincter obstructions were surgically managed. The outcomes for 4/6
      were favourable but 1/6 was euthanased intraoperatively, and 1/6 had a metastatic
      neoplasia and was euthanased 2 months postoperatively.

PMID- 20817528
TI  - Effect of enzyme therapy in juvenile patients with Pompe disease: a three-year
      open-label study.
AB  - Pompe disease is a rare neuromuscular disorder caused by deficiency of acid alpha
      glucosidase. Treatment with recombinant human alpha-glucosidase recently received
      marketing approval based on prolonged survival of affected infants. The current
      open-label study was performed to evaluate the response in older children (age
      5.9-15.2 years). The five patients that we studied had limb-girdle muscle
      weakness and three of them also had decreased pulmonary function in upright and
      supine position. They received 20-mg/kg recombinant human alpha-glucosidase every
      two weeks over a 3-year period. No infusion-associated reactions were observed.
      Pulmonary function remained stable (n = 4) or improved slightly (n = 1). Muscle
      strength increased. Only one patient approached the normal range. Patients
      obtained higher scores on the Quick Motor Function Test. None of the patients
      deteriorated. Follow-up data of two unmatched historical cohorts of adults and
      children with Pompe disease were used for comparison. They showed an average
      decline in pulmonary function of 1.6% and 5% per year. Data on muscle strength
      and function of untreated children were not available. Further studies are
      required.

PMID- 20817529
TI  - US forensic Y-chromosome short tandem repeats database.
AB  - A forensic Y-STR database generated in the US was compiled with profiles
      containing a portion or complete typing of 16 STR markers DYS19, DYS385, DYS389I,
      DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS456, DYS458,
      DYS635, DYS448, and Y GATA H4. There were 17,447 samples in the version of
      database in which 77% and 20% were collected in North America and Asia,
      respectively. The database was separated into six general populations, African
      American, Asian, Caucasian, Hispanic, Indian, and Native American. Each
      population was further classified into subgroups according to geographic regions.
      Some subgroups were tested, found to be homogenous and merged together. Allele
      and haplotype frequencies, as well as sample sizes were summarized. Of the full
      haplotypes (i.e., 16 STRs without missing data), 93.7% in total population were
      distinct, 92.9% were population specific, and 89.3% were only observed once. The
      majority of shared haplotypes were found among North American populations as a
      result of admixture lasting the past few hundred years. The power of
      discrimination (PD), coancestry coefficient (F(st)), and coefficient of gene
      differentiation (G(st)) at locus and haplotype levels were also calculated. The
      most polymorphic marker was DYS385; this marker contains a tandem duplication and
      actually is composed of two loci. Both G(st) and F(st) estimates were very small
      with haplotypes composed of a high number of STRs haplotypes (e.g., 10-16
      markers), although G(st) is slightly more conservative for these extended
      haplotypes. With Native American removed from the total population data set, the
      G(st) and F(st) estimates reduce further. PD was 0.9998 for the total population
      dataset for all 16 Y-STR markers. Three measures of Y-STR profile frequency were
      calculated: (1) unconditional haplotype frequency, (2) population substructure
      adjusted frequency, and (3) binomial upper bound of the haplotype frequency. The
      binomial upper bound is the most conservative estimate for most forensic
      applications. Estimates of the weight of a Y-STR haplotype can be estimated using
      population specific or total population databases.

PMID- 20817530
TI  - Defensive plant-ants stabilize megaherbivore-driven landscape change in an
      African savanna.
AB  - Tree cover in savanna ecosystems is usually regarded as unstable, varying with
      rainfall, fire, and herbivory. In sub-Saharan Africa, elephants (Loxodonta
      africana) suppress tree cover, thereby maintaining landscape heterogeneity by
      promoting tree-grass coexistence. In the absence of elephants, tree encroachment
      may convert savannas into closed-canopy woodlands; when elephants increase in
      abundance, intensified browsing pressure can transform savannas into open
      grasslands. We show that symbiotic ants stabilize tree cover across landscapes in
      Kenya by protecting a dominant tree from elephants. In feeding trials, elephants
      avoided plants with ants and did not distinguish between a myrmecophyte (the
      whistling-thorn tree [Acacia drepanolobium]) from which ants had been removed and
      a highly palatable, nonmyrmecophytic congener. In field experiments, elephants
      inflicted severe damage on whistling-thorn trees from which ants had been
      removed. Across two properties on which elephants increased between 2003 and
      2008, cover of whistling-thorn did not change significantly inside versus outside
      large-scale elephant exclusion fences; over the same period of time, cover of
      nonmyrmecophytes differed profoundly inside versus outside exclusion fences.
      These results highlight the powerful role that symbioses and plant defense play
      in driving tree growth and survival in savannas, ecosystems of global economic
      and ecological importance.

PMID- 20817531
TI  - Oocyte cohesin expression restricted to predictyate stages provides full
      fertility and prevents aneuploidy.
AB  - To ensure correct meiotic chromosome segregation, sister chromatid cohesion (SCC)
      needs to be maintained from its establishment in prophase I oocytes before birth
      until continuation of meiosis into metaphase II upon oocyte maturation in the
      adult. Aging human oocytes suffer a steep increase in chromosome missegregation
      and aneuploidy, which may be caused by loss of SCC through slow deterioration of
      cohesin [1-3]. This hypothesis assumes that cohesin expression in embryonic
      oocytes is sufficient to provide adequate long-term SCC. With increasing age,
      mouse oocytes deficient in the meiosis-specific cohesin SMC1beta massively lose
      SCC and chiasmata [3, 4]. To test the deterioration hypothesis, we specifically
      and highly efficiently inactivated the mouse Smc1beta gene at the primordial
      follicle stage shortly after birth, when oocytes had just entered meiosis I
      dictyate arrest. In the adult, however, irrespective of oocyte age, chiasma
      positions and SCC are normal. Frequency and size of litters prove full fertility
      even in aged females. Thus, SMC1beta cohesin needs only be expressed during
      prophase I prior to the primordial follicle stage to ensure SCC up to advanced
      age of mice.

PMID- 20817532
TI  - Modification of existing human motor memories is enabled by primary cortical
      processing during memory reactivation.
AB  - One of the most challenging tasks of the brain is to constantly update the
      internal neural representations of existing memories. Animal studies have used
      invasive methods such as direct microfusion of protein inhibitors to designated
      brain areas, in order to study the neural mechanisms underlying modification of
      already existing memories after their reactivation during recall [1-4]. Because
      such interventions are not possible in humans, it is not known how these neural
      processes operate in the human brain. In a series of experiments we show here
      that when an existing human motor memory is reactivated during recall,
      modification of the memory is blocked by virtual lesion [5] of the related
      primary cortical human brain area. The virtual lesion was induced by noninvasive
      repetitive transcranial magnetic stimulation guided by a frameless stereotactic
      brain navigation system and each subject's brain image. The results demonstrate
      that primary cortical processing in the human brain interacting with pre-existing
      reactivated memory traces is critical for successful modification of the existing
      related memory. Modulation of reactivated memories by noninvasive cortical
      stimulation may have important implications for human memory research and have
      far-reaching clinical applications.

PMID- 20817533
TI  - Age-related meiotic segregation errors in mammalian oocytes are preceded by
      depletion of cohesin and Sgo2.
AB  - BACKGROUND: The growing trend for women to postpone childbearing has resulted in
      a dramatic increase in the incidence of trisomic pregnancies. Maternal age
      related miscarriage and birth defects are predominantly a consequence of
      chromosome segregation errors during the first meiotic division (MI), which
      involves the segregation of replicated recombined homologous chromosomes. Despite
      the importance to human reproductive health, the events precipitating female age
      related meiotic errors are poorly understood. RESULTS: Here we use a long-lived
      wild-type mouse strain to show that the ability to segregate chromosomes
      synchronously during anaphase of MI declines dramatically during female aging.
      This is preceded by depletion of chromosome-associated cohesin in association
      with destabilization of chiasmata, the physical linkages between homologous
      chromosomes, and loss of the tight association between sister centromeres. Loss
      of cohesin is not due to an age-related decline in the ability of the spindle
      checkpoint to delay separase-mediated cleavage of cohesin until entry into
      anaphase I. However, we find that reduced cohesin is accompanied by depletion of
      Sgo2, which protects centromeric cohesin during MI. CONCLUSIONS: The data
      indicate that cohesin declines gradually during the long prophase arrest that
      precedes MI in female mammals. In aged oocytes, cohesin levels fall below the
      level required to stabilize chiasmata and to hold sister centromeres tightly
      together, leading to chromosome missegregation during MI. Cohesin loss may be
      amplified by a concomitant decline in the levels of the centromeric cohesin
      protector Sgo2. These findings indicate that cohesin is a key molecular link
      between female aging and chromosome missegregation during MI.

PMID- 20817534
TI  - Evidence that weakened centromere cohesion is a leading cause of age-related
      aneuploidy in oocytes.
AB  - Aneuploidy arising early in development is the leading genetic cause of birth
      defects and developmental disabilities in humans. Most errors in chromosome
      number originate from the egg, and maternal age is well established as the key
      risk factor. Although the importance of this problem for reproductive health is
      widely recognized, the underlying molecular basis for age-related aneuploidy in
      female meiosis is unknown. Here we show that weakened chromosome cohesion is a
      leading cause of aneuploidy in oocytes in a natural aging mouse model. We find
      that sister kinetochores are farther apart at both metaphase I and II, indicating
      reduced centromere cohesion. Moreover, levels of the meiotic cohesin protein REC8
      are severely reduced on chromosomes in oocytes from old mice. To test whether
      cohesion defects lead to the observed aneuploidies, we monitored chromosome
      segregation dynamics at anaphase I in live oocytes and counted chromosomes in the
      resulting metaphase II eggs. About 90% of age-related aneuploidies are best
      explained by weakened centromere cohesion. Together, these results demonstrate
      that the maternal age-associated increase in aneuploidy is often due to a failure
      to effectively replace cohesin proteins that are lost from chromosomes during
      aging.

PMID- 20817535
TI  - Laserlight cues for gait freezing in Parkinson's disease: an open-label study.
AB  - Freezing of gait (FOG) and falls are major sources of disability for Parkinson's
      disease (PD) patients, and show limited responsiveness to medications. We
      assessed the efficacy of visual cues for overcoming FOG in an open-label study of
      26 patients with PD. The change in the frequency of falls was a secondary outcome
      measure. Subjects underwent a 1-2 month baseline period of use of a cane or
      walker without visual cues, followed by 1 month using the same device with the
      laserlight visual cue. The laserlight visual cue was associated with a modest but
      significant mean reduction in FOG Questionnaire (FOGQ) scores of 1.25 +/- 0.48 (p
      = 0.0152, two-tailed paired t-test), representing a 6.6% improvement compared to
      the mean baseline FOGQ scores of 18.8. The mean reduction in fall frequency was
      39.5 +/- 9.3% with the laserlight visual cue among subjects experiencing at least
      one fall during the baseline and subsequent study periods (p = 0.002; two-tailed
      one-sample t-test with hypothesized mean of 0). Though some individual subjects
      may have benefited, the overall mean performance on the timed gait test (TGT)
      across all subjects did not significantly change. However, among the 4 subjects
      who underwent repeated testing of the TGT, one showed a 50% mean improvement in
      TGT performance with the laserlight visual cue (p = 0.005; two-tailed paired t
      test). This open-label study provides evidence for modest efficacy of a
      laserlight visual cue in overcoming FOG and reducing falls in PD patients.

PMID- 20817536
TI  - Cerebellar Purkinje cell loss is not pathognomonic of essential tremor.
AB  - BACKGROUND: Most of the literature on pathology of essential tremor (ET) has
      reported no consistent abnormalities. Some recent studies however indicate that
      cerebellar Purkinje cell (PC) loss is the pathological basis of ET in most
      patients. OBJECTIVE: To compare cerebellar PC loss in ET, with normal and tremor
      dominant Parkinson's disease [PD] control brains. METHODS: Cerebellar PC counts
      were performed in seven ET, six PD and two normal control brains. Three different
      counting methods - sectioned through nucleolus, through nucleus and through any
      part of PC body, were used to count the PC. RESULTS: There were individual
      differences in the PC counts both in the ET and the PD cases. In all three
      subgroups, there was a reduction in the number of PC with advancing age. When the
      individuals of comparable age in the three subgroups were considered, there was
      no clear distinction between ET, PD and normal control subjects. There was no
      association between the degree of PC loss and the severity or the duration of ET.
      CONCLUSION: Our study militates against the hypothesis that PC loss is
      pathognomonic of ET.

PMID- 20817537
TI  - Traumatic interhemispheric subdural haematoma: Study of 35 cases.
AB  - The clinical and radiological findings, management, and outcomes in 35 patients
      with traumatic interhemispheric subdural haematoma (ISH) were reviewed
      retrospectively. Twenty-five patients had favourable outcomes and 10 had poor
      outcomes. All patients were treated conservatively for ISH. Univariate analysis
      found that the Glasgow Coma Scale (GCS) score (p < 0.001), hypovolemic shock (p =
      0.018), skull fracture (p = 0.008), convexity or posterior fossa subdural
      haematoma (p = 0.008), and subarachnoid haemorrhage (SAH) were correlated with
      outcome (p < 0.001). Multivariate analysis showed that GCS score (p = 0.031; odds
      ratio [OR], 0.6; 95% confidence interval [CI], 0.3-0.9) and the presence of SAH
      (p = 0.023; OR, 14.2; 95% CI, 1.5-138.2) were significantly related to poor
      outcome. This study provides important information on the clinicoradiological
      findings and prognoses in patients with traumatic ISH.

PMID- 20817538
TI  - Structural resemblances and comparisons of the relative pharmacological
      properties of imatinib and nilotinib.
AB  - Although orphan drug applications required by the EMEA must include assessments
      of similarity to pre-existing products, these can be difficult to quantify. Here
      we illustrate a paradigm in comparing nilotinib to the prototype kinase inhibitor
      imatinib, and equate the degree of structural similarity to differences in
      properties. Nilotinib was discovered following re-engineering of imatinib,
      employing structural biology and medicinal chemistry strategies to optimise
      cellular potency and selectivity towards BCR-ABL1. Through evolving only to
      conserve these properties, this resulted in significant structural differences
      between nilotinib and imatinib, quantified by a Daylight-fingerprint-Tanimoto
      similarity coefficient of 0.6, with the meaning of this absolute measure being
      supported by an analysis of similarity distributions of similar drug-like
      molecules. This dissimilarity is reflected in the drugs having substantially
      different preclinical pharmacology and a lack of cross-intolerance in CML
      patients, which translates into nilotinib being an efficacious treatment for CML,
      with a favourable side-effect profile.

PMID- 20817539
TI  - Calculation of energy deposition, photon and neutron production in proton therapy
      of thyroid gland using MCNPX.
AB  - In this study, the MCNPX code has been used to simulate a proton therapy in
      thyroid gland, in order to calculate the proton energy deposition in the target
      region. As well as, we have calculated the photon and neutron production spectra
      due to proton interactions with the tissue. We have considered all the layers of
      tissue, from the skin to the thyroid gland, and an incident high energy pencil
      proton beam. The results of the simulation show that the best proton energy
      interval, to cover completely the thyroid tissue, is from 42 to 54 MeV, assuming
      that the thyroid gland has a 14 mm thickness and is located 11.2mm under the skin
      surface. The most percentage of deposited energy (78%) is related to the 54 MeV
      proton energy beam. Total photon and neutron production are linear and polynomial
      second order functions of the proton energy, respectively.

PMID- 20817540
TI  - Accumulation of radium in relation to some chemical analogues in Dicranopteris
      linearis.
AB  - This study elucidates the uptake and accumulation of radium in the field-growing
      fern Dicranopteris linearis by relating the radium concentration to some
      potential chemical analogues, including alkaline earth metals, rare earth
      elements, and some important heavy metals. Time-dependent accumulation of radium
      and these chemical analogues for D. linearis were described by the
      (228)Th/(228)Ra activity ratio, an index for inferring plant age. The correlation
      between radium and these elements was assessed by statistical analysis and used
      as a reference to elucidate the uptake and accumulation of radium in relation to
      the chemical analogues. Analytical and statistical results showed that the
      concentrations of alkaline earth metals (except for Mg) rare earth elements and
      some heavy metals in D. linearis increased linearly with plant age. These
      elements, exhibiting a similar accumulation pattern to radium and significant
      correlation coefficients with radium, were considered as the chemical analogues
      to radium. Additionally, the plant/soil concentration ratios (CRs) for radium and
      most of these analogues in D. linearis exceeded 1, consistent with the definition
      of hyper-accumulator plants.

PMID- 20817541
TI  - Investigation of alternative production routes of 99mTc: deuteron induced
      reactions on 100 Mo.
AB  - Activation cross sections of deuteron induced nuclear reactions on enriched
      (100)Mo have been studied up to 50 MeV using the stacked foil irradiation
      technique and gamma spectroscopy. The excitation functions for production of
      (99m)Tc, (ind99)Mo, (ind98m)Nb, (ind97mg)Nb radioisotopes were measured for the
      first time and compared with the results of the ALICE-D, EMPIRE-D and TALYS
      codes. Production possibilities of the medically important (99m)Tc are discussed.

PMID- 20817542
TI  - Hydrophilic polymer matrices in optical array sensing.
AB  - Whether in a glass chip or multi-well plate, differential array sensors are
      performed as a series of experiments and their output is compared among each
      other to obtain the differential signals evaluated by pattern recognition
      methods. To increase the practicality of performing a large number of experiments
      the sensor elements are often used as semi-wet gels displaying properties of both
      the solution and the solid state. Due to their semi-wet nature, such array
      sensors are easier to handle while offering a mechanical support, the affinity of
      hydrophilic matrices for water aids in analyte transport, and the tunable
      hydrophilic/hydrophobic nature of the matrices can be used adjusting the
      preference of the chemosensor membrane for different analytes.

PMID- 20817543
TI  - Malignant solitary fibrous tumor of the esophagus.
AB  - Solitary fibrous tumor (SFT) of the esophagus has been very rarely reported in
      literature. Herein, we report a case of a successful surgically treated malignant
      solitary fibrous tumor of the esophagus. A 36-year-old woman was admitted at our
      hospital with an erroneous ultrasound-based diagnosis of cervico-mediastinal
      goiter. Surprisingly, the preoperative diagnostic work-up, including a computed
      tomographic chest scan, endoscopy, and endoscopic ultrasonography, revealed a
      pedunculated intraluminal mass in the esophagus. The tumor was radically removed
      through left antero-lateral cervicotomy. Pathologic and immunohistochemical
      examination was concluded for a malignant SFT, a rare variant not previously
      described in relation to the esophagus. The patient underwent adjuvant
      radiotherapy and is alive with no signs of tumor recurrence 32 months after
      surgery.

PMID- 20817544
TI  - How close are we to nitrogen-fixing cereals?
AB  - Engineering nitrogen-fixing cereals is essential for sustainable food production
      for the projected global population of 9 billion people in 2050. This process
      will require engineering cereals for nodule organogenesis and infection by
      nitrogen-fixing bacteria. The symbiosis signalling pathway is essential to
      establish both bacterial infection and nodule organogenesis in legumes and is
      also necessary for the establishment of mycorrhizal colonisation. Hence this
      signalling pathway is also present in cereals and it should be feasible to
      engineer this signalling pathway for cereal recognition of nitrogen-fixing
      bacteria. However, establishing a fully function nitrogen-fixing symbiosis in
      cereals will probably require additional genetic engineering for bacterial
      colonisation and nodule organogenesis.

PMID- 20817545
TI  - Prevention and management of major side effects of targeted agents in breast
      cancer.
AB  - Targeted therapies have evolved dramatically over the last few years. The
      heterogeneity of breast cancer is now understood on a molecular level, and
      different targeted therapeutic strategies have been approved in an attempt to
      tailor treatment strategies. Although the incidence of side effects is expected
      to be low due to target specificity, this is not always the case. Adverse events
      such as congestive heart failure and life threatening diarrhoea are sometimes
      observed because of off-target drug effects. In this article, we discuss the
      incidence, prevention and management of serious adverse events associated with
      trastuzumab, lapatinib, and bevacizumab. We critically analyse the available
      evidence and provide some insights on how to manage these toxicities in the
      clinical setting.

PMID- 20817546
TI  - The role of seasonal influenza vaccination in preventing pandemic 2009 influenza
      (H1N1) during a school outbreak.

PMID- 20817547
TI  - The detection of glycosphingolipids in brain tissue sections by imaging mass
      spectrometry using gold nanoparticles.
AB  - Glycosphingolipids (GSLs) are amphiphilic molecules consisting of a hydrophilic
      carbohydrate chain and a hydrophobic ceramide moiety. They appear to be involved
      primarily in biological processes such as cell proliferation, differentiation,
      and signaling. To investigate the mechanism of brain function in more detail, a
      more highly sensitive method that would reveal the GSL distribution in the brain
      is required. In this report, we describe a simple and efficient method for
      mapping the distribution and localization of GSLs present in mouse brain sections
      using nanoparticle-assisted laser desorption/ionization imaging mass spectrometry
      (IMS). We have developed and tested gold nanoparticles (AuNPs) as a new matrix to
      maximize the detection of GSLs. A matrix of AuNPs modified with alkylamine was
      used to detect various GSLs, such as minor molecular species of sulfatides and
      gangliosides, in mouse brain sections; these GSLs were hardly detected using 2,5
      dihydroxybenzoic acid (DHB), which is the conventional matrix for GSLs. We
      achieved approximately 20 times more sensitive detection of GSLs using AuNPs
      compared to a DHB matrix. We believe that our new approach using AuNPs in IMS
      could lead to a new strategy for analyzing basic biological mechanisms and
      several diseases through the distribution of minor GSLs.

PMID- 20817548
TI  - A near infra-red spectroscopy study of the effects of pre-frontal single and
      paired pulse transcranial magnetic stimulation.
AB  - OBJECTIVE: Concentration changes in hemoglobin following single and paired pulse
      (2 and 15 ms inter-stimulus interval) transcranial magnetic stimulation (TMS) was
      investigated using near infra-red spectroscopy (NIRS). METHODS: TMS was delivered
      to left pre-frontal cortex at typical intensities used in neuroscience research
      and concentrations of deoxyhemoglobin (Hb), oxyhemoglobin (HbO) and total
      hemoglobin (HbT) were measured. RESULTS: Significant drops in concentration of
      HbO and HbT were observed and while there was no effect of the different pulse
      types on amplitude, there was a difference in the time taken to return to
      baseline. CONCLUSIONS: The changes observed imply that in pre-frontal cortex, the
      different TMS pulse types result in differential effects on oxygen consumption.
      SIGNIFICANCE: This study aids our understanding of the physiological effects of
      single and paired pulse TMS.

PMID- 20817549
TI  - Olfactory dysfunction in narcolepsy with cataplexy.
AB  - BACKGROUND: Narcolepsy-cataplexy (NC) is caused by the loss of hypocretin
      neurons. Several lines of evidence suggest a role for hypocretin in olfactory
      function. Recent data have documented that NC is associated with olfactory
      dysfunction but smell testing has been performed only in small studies. METHODS:
      One hundred thirty NC patients were recruited from two sleep disorders centers in
      France and Italy. They were compared to 129 age- and gender-matched healthy
      controls on two well standardized olfactory tests: the Sniffin' Sticks (France)
      and Brief Smell Identification (Italy) tests. Olfactory dysfunction was defined
      as a score below the tenth centile on each smell test. RESULTS: Altogether,
      olfactory deficit was higher in NC compared to controls (23.8% vs. 13.9%,
      p=0.042, OR: 1.93 CI 95%, 1.01-3.66); olfactory identification deficit was found
      in 35.8% of NC compared to 13.9% of controls in Italy (p=0.03), and in 11.2% vs.
      8.2% in France (NS). Using the Sniffin' Sticks (France) we noted significant
      lower discrimination and global olfactory performance in NC compared to controls.
      Based on standardized criteria for Sniffin' Sticks, none of the NC patients or
      controls presented anosmia or severe hyposmia, but 6.4% of the NC patients had
      moderate hyposmia and 22.2% mild, in contrast to 6.4% of controls with only mild
      hyposmia. Finally except tobacco smoking, clinical potential factors including
      age at onset and severity of the condition did not modify olfactory performances
      in the whole population. CONCLUSION: Our study is the largest investigation of
      olfactory performance in NC showing that the disease perse is associated with
      mild/moderate dysfunction in a quarter of patients.

PMID- 20817550
TI  - Altered cortical excitability in patients with untreated obstructive sleep apnea
      syndrome.
AB  - OBJECTIVE: To investigate cortical excitability in patients with obstructive
      sleep apnea syndrome (OSAS) during wakefulness. METHODS: The authors recruited 45
      untreated severe OSAS (all males, mean age 47.2 years, mean apnea-hypopnea
      index=44.6h(-1)) patients and 44 age-matched healthy male volunteers (mean apnea
      hypopnea index=3.4h(-1)). The TMS parameters measured were resting motor
      threshold (RMT), motor evoked potential (MEP) amplitude, cortical silent period
      (CSP), and short-interval intracortical inhibition (SICI) and intracortical
      facilitation (ICF). These parameters were measured in the morning (9-10 am) more
      than 2h after arising and the parameters of patients and controls were compared.
      The Epworth Sleepiness Scale (ESS) and the Stanford Sleepiness Scale (SSS) were
      also measured before the TMS study. RESULTS: OSAS patients had a significantly
      higher RMT and a longer CSP duration (t-test, p<0.001) compared to healthy
      volunteers. No significant difference was observed between MEP amplitudes at any
      stimulus intensity or between the SICI (2, 3, 5ms) and ICF (10, 15, 20ms) values
      of OSAS patients and healthy volunteers (p>0.05). CONCLUSIONS: This TMS-based
      study suggests that untreated severe OSAS patients have imbalanced cortical
      excitabilities that enhanced inhibition or decreased brain excitability when
      awake during the day.

PMID- 20817551
TI  - Sleep disorders and daytime sleepiness in children with attention
      deficit/hyperactivity disorder: a two-night polysomnographic study with a
      multiple sleep latency test.
AB  - OBJECTIVE: To evaluate sleep macrostructure, sleep disorders incidence and
      daytime sleepiness in attention-deficit/hyperactivity disorder (ADHD) affected
      children compared with controls. METHODS: Thirty-one patients (26 boys, 5 girls,
      mean age 9.3+/-1.7, age range 6-12 years) with ADHD diagnosed according to DSM-IV
      criteria, without comorbid psychiatric or other disorders, as never before
      pharmacologically treated for ADHD. The controls were 26 age- and sex-matched
      children (22 boys, 4 girls, age range 6-12 years, mean age 9.2+/-1.5). Nocturnal
      polysomnography (PSG) was performed for two nights followed by the multiple sleep
      latency test (MSLT). RESULTS: No differences between the two groups comparing
      both nights were found in the basic sleep macrostructure parameters or in the
      time (duration) of sleep onset. A first-night effect on sleep variables was
      apparent in the ADHD group. Occurrence of sleep disorders (sleep-disordered
      breathing [SDB], periodic limb movements in sleep [PLMS], parasomnias) did not
      show any significant differences between the investigated groups. A statistically
      significant difference (p=0.015) was found in the trend of the periodic limb
      movement index (PLMI) between two nights (a decrease of PLMI in the ADHD group
      and an increase of PLMI in the control group during the second night). While the
      mean sleep latency in the MSLT was comparable in both groups, children with ADHD
      showed significant (sleep latency) inter-test differences (between tests 1 and 2,
      1 and 4, 1 and 5, p<0.01). CONCLUSION: After the inclusion of adaptation night
      and exclusion of psychiatric comorbidities, PSG showed no changes in basic sleep
      parameters or sleep timing, or in the frequency of sleep disorders (SDB, PLMS) in
      children with ADHD compared with controls, thus not supporting the hypothesis
      that specific changes in the sleep macrostructure and sleep disturbances are
      connected with ADHD. A first-night effect on sleep variables was apparent only in
      the ADHD group. Though we found no proof of increased daytime sleepiness in
      children with ADHD against the controls, we did find significant vigilance
      variability during MSLT in the ADHD group, possibly a sign of dysregulated
      arousal.

PMID- 20817552
TI  - Video-clinical corners. Snoring, penile erection and loss of reflexive
      consciousness during REM sleep behavior disorder.

PMID- 20817553
TI  - Violent behavior during sleep: prevalence, comorbidity and consequences.
AB  - BACKGROUND: Violent behaviors during sleep (VBS) are consequences of several
      sleep disorders but have received little attention in epidemiologic studies. This
      study aims to determine the prevalence of VBS in the general population and their
      comorbidity, familial links, course and treatment. METHODS: Random stratified
      sample of 19,961 participants, 15 years and older, from the general population of
      Finland, Germany, Italy, Portugal, Spain and the United Kingdom were interviewed
      by telephone using the Sleep-EVAL Expert System. They answered a questionnaire on
      VBS, their consequences and treatment. Parasomnias and sleep and mental disorders
      were also evaluated. RESULTS: VBS was reported by 1.6% (95% confidence interval:
      1.4-1.7%) of the sample. VBS was higher in subjects younger than 35 years. During
      VBS episodes, 78.7% of VBS subjects reported vivid dreams and 31.4% hurt
      themselves or someone else. Only 12.3% of them consulted a physician for these
      behaviors. In 72.8% of cases, VBS were associated with other parasomnias (highest
      odds of VBS for sleepwalking and sleep terrors). Family history of VBS,
      sleepwalking and sleep terrors was reported more frequently in VBS than in non
      VBS subjects with odds of 9.3, 2.0 and 4.2, respectively. CONCLUSIONS: VBS are
      frequent in the general population and often associated with dream-enactment,
      sleepwalking and sleep terrors. High frequency of VBS, sleepwalking and sleep
      terrors in family of VBS subjects indicated that some families have a greater
      vulnerability to sleep disorders involving motor dyscontrol. Subjects who
      consulted a physician for these behaviors mostly received inappropriate or no
      support, indicating a lack of knowledge about VBS.

PMID- 20817554
TI  - Risk factors associated with short sleep duration among Chinese school-aged
      children.
AB  - OBJECTIVES: To examine risk factors regarding short sleep duration among Chinese
      school-aged children. METHODS: A random sample of 20,778 children aged around 5
      11years participated in a cross-sectional survey, which was conducted in eight
      cities of China in 2005. A parent-administered questionnaire was used to collect
      information on children's sleep duration and possible related factors from eight
      domains. Short sleep duration was defined as total sleep duration <9h per day.
      RESULTS: In all, 28.3% of the sampled children slept <9h per day. The
      multivariate logistic regression identified, after adjusting for demographic and
      socioeconomic variables, factors associated with short sleep duration: more
      television viewing during weekdays (OR=1.21, p=0.004), more frequent
      computer/internet using (OR=1.17, p=0.006), earlier school starting time
      (OR=1.10, p=0.020), more time on homework during weekdays (OR=1.66, p<0.001) and
      weekends (OR=1.14, p=0.001), poor bedtime hygiene (e.g., having drinks with
      caffeine after 6:00PM [OR=1.22, p<0.001], doing exciting activities during
      bedtime [OR=1.16, p<0.001], and irregular bedtime [OR=1.55, p<0.001]), and
      shorter sleep duration of parents (mother: OR=1.31, p<0.001 for sleep duration
      <6h and OR=1.24, p=0.006 for 6-8h; father: OR=1.52, p<0.001 for <6h and OR=1.19,
      p<0.001 for 6-8h). CONCLUSIONS: Factors associated with sleep duration covered
      multidimensional domains among school-aged children. Compared to sleep
      environments and chronic health problems, school schedules, lifestyle patterns,
      and parents' sleep habits had greater impact on children's sleep duration,
      indicating the existing chronic sleep loss in school children could be, at least
      partly, intervened by reducing the use of visual technologies, by changing the
      school schedules, by improving the sleep hygiene routine, and by regulating
      parents' sleep habits.

PMID- 20817555
TI  - Dinoflagellates associated with freshwater sponges from the ancient lake baikal.
AB  - Dinoflagellates are a diverse group of protists that are common in both marine
      and freshwater environments. While the biology of marine dinoflagellates has been
      the focus of several recent studies, their freshwater relatives remain little
      investigated. In the present study we explore the diversity of dinoflagellates in
      Lake Baikal by identifying and analyzing dinoflagellate sequences for 18S rDNA
      and ITS-2 from total DNA extracted from three species of endemic Baikalian
      sponges (Baikalospongia intermedia,Baikalospongia rectaand Lubomirskia
      incrustans). Phylogenetic analyses of these sequences revealed extensive
      dinoflagellate diversity in Lake Baikal. We found two groups of sequences
      clustering within the order Suessiales, known for its symbiotic relationships
      with various invertebrates. Thus they may be regarded as potential symbionts of
      Baikalian sponges. In addition,Gyrodinium helveticum, representatives from the
      genus Gymnodinium, dinoflagellates close to the family Pfiesteriaceae, and a few
      dinoflagellates without definite affiliation were detected. No pronounced
      difference in the distribution of dinoflagellates among the studied sponges was
      found, except for the absence of the Piscinoodinium-like dinoflagellates inL.
      incrustans. To the best of our knowledge, this is the first study of the
      diversity of dinoflagellates in freshwater sponges, the first systematic
      investigation of dinoflagellate molecular diversity in Lake Baikal and the first
      finding of members of the order Suessiales as symbionts of freshwater
      invertebrates.

PMID- 20817557
TI  - Does early morphology provide additional selection power to blastocyst selection
      for transfer?
AB  - Routine early developmental parameters are widely used in IVF centres to evaluate
      embryo development and fresh single-blastocyst transfer currently seems superior
      to single-embryo transfer. Would early morphological parameters help to choose
      the single blastocyst to be transferred, thereby improving the chances of
      implantation and live birth rate? This prospective observational study analysed
      the individual outcomes of 2617 embryos from 511 IVF couples scheduled for a
      single-blastocyst transfer. Embryo and blastocyst scores were constructed. There
      was a clear relationship between the kinetics and morphology of blastocysts and
      further implantation and live birth rate. There was a limited predictive value of
      embryo score with regard to blastocyst development and growth kinetics. Implanted
      and non-implanted blastocysts showed similar embryo scores. Thus usual
      morphological parameters on days 1 and 2 seem to have no additional value in
      indicating the right blastocyst to transfer. Non-invasive approaches might be
      helpful to increase the chances of implantation in the future.

PMID- 20817556
TI  - Adaptive immunity and adipose tissue biology.
AB  - Studies of immunity typically focus on understanding how hematopoietic cells
      interact within conventional secondary lymphoid tissues. However, immune
      reactions and their regulation occur in various environments within the body.
      Adipose tissue is one tissue that can influence and be influenced by adjacent and
      embedded lymphocytes. Despite the abundance and wide distribution of such tissue,
      and despite a growing obesity epidemic, studies of these interactions have been
      only marginally appreciated in the past. Here, we review advances in
      understanding of lymphoid structures within adipose tissue, the relationship
      between adipose tissue and adaptive immune function, and evidence for how this
      relationship contributes to obesity-associated diseases.

PMID- 20817558
TI  - Single-session percutaneous ethanol ablation of early-stage hepatocellular
      carcinoma with a multipronged injection needle: results of a pilot clinical
      study.
AB  - PURPOSE: To investigate the feasibility, safety, and efficacy of single-session
      ethanol ablation with multipronged needles in the treatment of early-stage
      hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A pilot clinical study
      enrolled 20 patients with Child-Pugh A-B cirrhosis (15 men and 5 women 53-84
      years old [mean 70.3 years old +/- 8.3, median 72 years old]) and with 25 HCC
      tumors 1.2-3.8 cm in longest diameter (mean 2.3 cm +/- 0.6) located in
      unfavorable locations for radiofrequency (RF) ablation. Ethanol ablation was
      performed under moderate sedation using a multipronged injection needle (Quadra
      Fuse; REX Medical, Conshohocken, Pennsylvania) and ultrasound guidance. Follow-up
      period ranged from 12-24 months (mean 15.9 months +/- 4.6, median 16 months) and
      included contrast-enhanced computed tomography (CT) or magnetic resonance (MR)
      imaging performed 1 month after treatment and at 3-month intervals thereafter.
      RESULTS: The treatment protocol was successfully completed in all patients
      (technical success rate 100%). No major complications were observed. A single
      treatment session with injection of 5-26 mL of ethanol (mean 9.5 mL +/- 5.5)
      resulted in complete tumor ablation at 1 month CT or MR imaging in 21 (84%) of 25
      tumors. A second treatment session increased the number of tumors with complete
      response (CR) to 23 of 25 (primary effectiveness rate 92%). Tumor progression was
      observed in three cases during the follow-up period, for a rate of confirmed CR
      of 80% (20 of 25). CONCLUSIONS: Ethanol ablation performed with a multipronged
      injection needle was not associated with any major complications and resulted in
      a high rate of confirmed CR. This technique offers an alternative to RF ablation
      for single-session treatment of early-stage HCC.

PMID- 20817559
TI  - Protective role of zinc picolinate on cisplatin-induced nephrotoxicity in rats.
AB  - OBJECTIVE: Cisplatin-induced nephrotoxicity is related to an increase in lipid
      peroxidation, oxygen-free radicals, and inflammation in kidney. Zinc is an
      antioxidant and has anti-inflammatory action. To date, the protective role of
      zinc picolinate on cisplatin-induced renal injury has not been investigated. The
      purpose of the present study was to examine the effect of zinc picolinate on
      cisplatin-induced renal injury. METHODS: Male Wistar rats (n = 28, 8-week-old,
      weighing 200 to 220 g) were divided into four groups consisting of 7 rats each:
      control, zinc picolinate (6 mg Zn kg(-1) BW i.p.), cisplatin (7 mg kg(-1)BW i.p.,
      single dose) and cisplatin plus zinc picolinate. RESULTS: A single dose of
      cisplatin resulted in an increase in malondialdehyde, 8-isoprostane, and tumor
      necrosis factor-alpha levels of kidney and significantly deranged renal function
      (urea-N and creatinine; P < .0001). Zinc picolinate treatment significantly
      reduced urea-N, creatinine, malondialdehyde, 8-isoprostane, and tumor necrosis
      factor-alpha -alpha levels. Concentration of zinc in kidney was increased
      significantly after zinc picolinate supplementation; however, Fe and Cu levels
      did not change. Expression of Bax in kidney increased with cisplatin
      administration, and this could be prevented by zinc picolinate treatment (P <
      .001). However, bcl-2 expression did not change by zinc or cisplatin treatment (P
      > .05). The expression of heat shock proteins 60 and 70 in kidney was increased
      after cisplatin treatment compared with the levels in the control (P < .01), and
      this increase could be prevented by the zinc picolinate treatment (P < .05).
      CONCLUSIONS: These results suggest that zinc picolinate may be a potential
      preventive agent in cisplatin-induced renal injury through decreasing oxidative
      stress and inflammation.

PMID- 20817560
TI  - Vitamin D deficiency, inflammation, and albuminuria in chronic kidney disease:
      complex interactions.
AB  - OBJECTIVE: Vitamin D may promote cardiovascular health in general population and
      in chronic kidney disease (CKD) through inhibition of the renin-angiotensin
      system and anti-inflammatory effects. Although proteinuria is a marker of kidney
      and cardiovascular disease, few studies have examined vitamin D levels,
      inflammation, and proteinuria simultaneously in CKD. We evaluated the
      relationship between calcidiol (25D), calcitriol (1,25D), inflammation, and
      albuminuria in Study of Early Evaluation of Kidney Disease, a multicenter CKD
      cohort. DESIGN: A cross-sectional study was carried out. PARTICIPANTS: A total of
      1,847 participants were studied, of which 387 were randomly selected for
      inflammatory biomarker assessment. PREDICTORS AND OUTCOMES: The primary
      predictors were 25D and 1,25D. The outcome was albuminuria (urine albumin to
      creatinine ratio [UACR]: >30 mg/g). RESULTS: Albuminuric patients were more
      likely to have decreased 25D and 1,25D levels and higher interleukin-6 (IL-6)
      levels compared with normoalbuminuric patients. The lowest tertiles of 25D and
      1,25D were associated with 2 to 3 times increased odds of albuminuria compared
      with the highest tertiles when adjusted for age, gender, race, systolic blood
      pressure, and diabetes (OR for 25D: 3.0; 95% CI: 1.3 to 7.0; OR for 1,25D: 2.6;
      95% CI: 1.7 to 3.9). In analogous linear regression models, 25D and 1,25D were
      significantly associated with log UACR (P < .0001, for both). In participants for
      whom inflammatory markers were measured, demographics-adjusted linear regression
      models that included IL-6 described attenuation of the relationship between 25D,
      1,25D, and UACR. CONCLUSIONS: Low 25D and 1,25D levels are independently
      associated with albuminuria. IL-6 may be an important intermediary between
      vitamin D deficiency and albuminuria, or vitamin D deficiency may contribute to
      inflammation and subsequent albuminuria.

PMID- 20817561
TI  - Patent foramen ovale and major pulmonary embolism.

PMID- 20817562
TI  - Association of preanesthesia hypertension with adverse outcomes.
AB  - OBJECTIVE: To investigate the incidence of preanesthesia hypertension, case
      cancellation for hypertension, and association with postoperative outcomes.
      DESIGN: Retrospective descriptive, univariate, and multivariate analyses of
      electronic anesthesia and hospital records. SETTING: A large urban academic
      medical center. PARTICIPANTS: Adult elective surgical patients with preinduction
      blood pressure (BP) >140/90 mmHg during calendar years 2002 to 2008.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Preinduction hypertension was
      present in 21,126 of 209,985 (10%) patients, and the incidence of adverse
      outcomes (elevated troponin or in-hospital death) was 1.3% overall and 2.8% for
      the subset of patients with baseline systolic BP >200 mmHg. Independent
      predictors of adverse outcome included increased baseline systolic BP,
      intraoperative diastolic BP <85 mmHg, increased intraoperative heart rate, blood
      transfusion, and anesthetic technique, controlling for standard risk factors. A
      total of 69 hypertensive patients (0.3%) had surgery cancelled before the
      induction of anesthesia; 29 of these cancellations occurred among the 1,330
      patients with baseline SBP >200 mmHg (2.2%). Among 42 "cancelled" patients who
      returned for surgery hours to years later, the average preinduction BP was
      192/102 mmHg, and adverse cardiovascular outcomes occurred in 4.8%. CONCLUSIONS:
      The increasing severity of preinduction hypertension was an independent risk
      factor for postoperative myocardial injury/infarction or in-hospital death. Only
      a small percentage of cases with patients presenting with severe hypertension
      were cancelled, and the delay of surgery did not result in interval normalization
      of blood pressure.

PMID- 20817563
TI  - Publication trends in the journal of cardiothoracic and vascular anesthesia: a 10
      year analysis.
AB  - OBJECTIVE: Good quality clinical research in anesthesiology is now performed all
      over the world. The aim of this article was to present and analyze the scientific
      contributions published in the Journal of Cardiothoracic and Vascular Anesthesia
      and to give a structured view focused on the countries where these studies were
      performed. DESIGN: Bibliometric analysis. SETTING: Teaching hospital.
      PARTICIPANTS: None. INTERVENTIONS: The authors analyzed the geographic
      distribution of the authors publishing in cardiac anesthesia. MEASUREMENTS AND
      MAIN RESULTS: Data were obtained from the Scopus database. All works belonging to
      document-type articles, reviews, letters, and editorials published over a 10-year
      period (2000-2009) in the Journal of Cardiothoracic and Vascular Anesthesia
      (JCVA) were tracked. For each article, the country of origin of the corresponding
      author was retrieved. JCVA published 1,816 articles from 45 different countries.
      The United States accounted for 43.8% of the total, followed by India (8.3%),
      Germany (5.5%), United Kingdom (4.7%), and Italy (4.4%). CONCLUSIONS: JCVA has a
      widespread influence and receives contributions from all over the world. More and
      more biomedical research is conducted outside North America and Europe, with
      India leading the group of "rest of the world" countries. The recent development
      of Asian countries clearly challenges North America and European countries that
      can no longer ignore the scientific contribution from these parts of the world.
      With this in mind, some journals such as JCVA are giving voice to these prolific
      countries, which represents a fundamental forum for these newcomers to the field
      of cardiac anesthesia.

PMID- 20817565
TI  - A structured 3-step approach to evaluate cardiac recovery with continuous flow
      circulatory support.

PMID- 20817564
TI  - End-of-life decision making and implementation in recipients of a destination
      left ventricular assist device.
AB  - BACKGROUND: The use of left ventricular assist devices (LVADs) as destination
      therapy (DT) is increasing and has proven beneficial in prolonging survival and
      improving quality of life in select patients with end-stage heart failure.
      Nonetheless, end-of-life (EOL) issues are inevitable and how to approach them
      underreported. METHODS: Our DT data registry was queried for eligible patients,
      defined as those individuals who actively participated in EOL decision making.
      The process from early EOL discussion to palliation and death was reviewed. We
      recorded the causes leading to EOL discussion, time from EOL decision to
      withdrawal and from withdrawal to death, and location. Primary caregivers were
      surveyed to qualify their experience and identify themes relevant to this
      process. RESULTS: Between 1999 and 2009, 92 DT LVADs were implanted in 69
      patients. Twenty patients qualified for inclusion (mean length of support: 833
      days). A decrease in quality of life from new/worsening comorbidities usually
      prompted EOL discussion. Eleven patients died at home, 8 in the hospital and 1 in
      a nursing home. Time from EOL decision to LVAD withdrawal ranged from <1 day to 2
      weeks and from withdrawal until death was <20 minutes in all cases. Palliative
      care was provided to all patients. Ongoing assistance from the healthcare team
      facilitated closure and ensured comfort at EOL. CONCLUSIONS: With expanding
      indications and improved technology, more DT LVADs will be implanted and for
      longer durations, and more patients will face EOL issues. A multidisciplinary
      team approach with protocols involving DT patients and their families in EOL
      decision making allows for continuity of care and ensures dignity and comfort at
      EOL.

PMID- 20817566
TI  - Chronic extra-aortic balloon counterpulsation: first-in-human pilot study in end
      stage heart failure.
AB  - BACKGROUND: Some patients continue to have significant heart failure symptoms
      despite optimal medical therapy. METHODS: We describe a first-in-human experience
      with an implantable non-blood-contacting extra-ascending aortic counterpulsation
      heart assist system (C-Pulse) in 5 end-stage heart failure patients, aged 54 to
      73 years. RESULTS: All patients improved by 1 NYHA class and improvements in
      invasive hemodynamics were documented in 3 patients. Three of 5 patients (60%)
      had infectious complications. Two patients were explanted at 5 and 7 weeks,
      respectively, as a result of mediastinal infection related to the implant
      procedure. One patient was successfully transplanted at 1 month and 1 remained
      hemodynamically improved on the device at 6 months but suffered infective
      complications. The device and protocol have been modified as a result of this
      pilot study with a further multicenter safety study underway. CONCLUSIONS:
      Although feasibility of this device is suggested by this pilot study, safety and
      efficacy will need to be examined in a larger cohort with longer follow-up.

PMID- 20817567
TI  - Impaired endothelial progenitor cell recruitment may contribute to heart
      transplant microvasculopathy.
AB  - BACKGROUND: Circulating progenitor cells (PCs) may play a role in the
      pathogenesis of cardiac allograft vasculopathy, the leading cause of morbidity
      and mortality in heart transplantation (HTx). We assessed the relationship
      between circulating PCs and their incorporation into allografts and coronary
      microvascular function in HTx. METHODS: PCs were quantified by flow cytometry on
      the basis of the surface expression of CD34, CD133, and kinase domain receptor
      (KDR) antigens. Biopsy specimens at 2 different times were examined.
      Immunohistochemistry for the stem cell marker c-Kit, endothelial PC (EPC) marker
      KDR, and CD34 was performed in serial sections in all specimens. Cells positive
      for each marker were counted in all specimen area sections, and the number
      obtained was corrected by area section. Coronary flow in the left anterior
      descending coronary artery was detected at rest and during intravenous adenosine
      by transthoracic echocardiography. Coronary flow reserve (CFR) was the ratio of
      hyperemic diastolic mean velocity (DMV)/resting DMV. RESULTS: CFR was measured in
      29 patients and was abnormal (CFR < 2) in 6 (Group A) and normal in 23 (Group B).
      CFR was lower in Group A (1.5 +/- 0.1 vs 3.3 +/- 0.8, p < 0.0001). CD34(+)KDR(+),
      CD133(+)KDR(+), and CD34(+)CD133(+)KDR(+) cell counts were lower in Group A (p <
      0.05). EPCs in biopsy sections tended to be lower in Group A (p = 0.06) and
      correlated to circulating CD133(+)KDR(+) and CD34(+)CD133(+)KDR(+) (p = 0.003 and
      p = 0.052, respectively). CONCLUSIONS: EPCs are decreased in the circulation and
      in the allograft in patients with microvasculopathy. Defective mobilization and
      engraftment of EPCs may be involved in the pathogenesis of cardiac allograft
      vasculopathy.

PMID- 20817568
TI  - Infective endocarditis of the Dacron patch-a report of 13 cases at autopsy.
AB  - AIMS: One of the complications of using a synthetic material as a patch in
      correction of left-to-right shunts is the development of infection. This is an
      autopsy report of 13 patients who developed infective endocarditis of the Dacron
      patch as a postoperative complication. METHODS: We retrospectively reviewed the
      autopsy records of patients with infective endocarditis over a 15-year period
      (1994-2008) and selected cases with Dacron-patch infective endocarditis. The
      patch infective endocarditis was classified into early-onset and late-onset
      infective endocarditis. RESULTS: Patch infective endocarditis was seen in 13
      patients affecting the patches covering an atrial septal defect and 12
      ventricular septal defects. There were nine males and four females, with a mean
      age of 13.1 years. The episodes occurred 2 to 118 days (mean of 30) after
      operation, with early-onset infective endocarditis in 10 and late-onset infective
      endocarditis in three patients. Postoperative wound infection had been present in
      eight. The organisms isolated or demonstrated on microscopy included
      Staphylococcus aureus (5), gram-positive cocci (4), Pseudomonas (2), Aspergillus
      species (1), and Candida species (1). Death was related to embolization and/or
      accompanying septicemia. CONCLUSIONS: Correction of simple or complex congenital
      cardiac defects offers new substrates for organisms to colonize resulting in
      infective endocarditis, which are often difficult to treat.

PMID- 20817569
TI  - Extracellular matrix remodeling and cell phenotypic changes in dysplastic and
      hemodynamically altered semilunar human cardiac valves.
AB  - INTRODUCTION: Congenital cardiac valve disease is common, affecting ~1% of the
      population, with substantial morbidity and mortality, but suboptimal treatment
      options. Characterization of the specific matrix and valve cell phenotypic
      abnormalities in these valves could lend insight into disease pathogenesis and
      potentially pave the way for novel therapies. METHODS: Thirty-five human aortic
      and pulmonic valves were categorized based on gross and microscopic assessment
      into control valves (n=21); dysplastic valves, all except one also displaying
      hemodynamic changes (HEMO/DYSP, n=6); and hemodynamically altered valves (HEMO,
      n=8). Immunohistochemistry was performed on valve sections and flow cytometry on
      valvular interstitial cells. RESULTS: While both hemodynamically altered aortic
      and pulmonic valves demonstrated increased collagen turnover and cell activation,
      prolyl 4-hydroxylase and hyaluronan increased in hemodynamically altered aortic
      valves but decreased in hemodynamically altered pulmonic valves relative to
      control valves (P<.001). HEMO/DYSP aortic valves demonstrated decreased collagen
      and elastic fiber synthesis and turnover compared to both hemodynamically altered
      aortic valves and control aortic valves (each P<.006). Valvular interstitial
      cells from both hemodynamically altered and HEMO/DYSP pulmonic valves showed
      altered cell phenotype compared to control valves (each P<.032), especially
      increased non-muscle myosin. Furthermore, valvular interstitial cells from
      hemodynamically altered pulmonic valves and HEMO/DYSP aortic and pulmonic valves
      each demonstrated greater size and complexity compared to control valves (each
      P<.05). CONCLUSIONS: Dysplastic semilunar valves displayed alterations in
      collagen and elastic fiber turnover that were distinct from valves similarly
      exposed to altered hemodynamics as well as to control valves. These results
      demonstrate that dysplastic valves are not simply valves with gross changes or
      loss of leaflet layers, but contain complex matrix and cell phenotype changes
      that, with future study, could potentially be targets for novel nonsurgical
      treatments.

PMID- 20817570
TI  - On-line chemiluminescence determination of mitoxantrone by capillary
      electrophoresis.
AB  - A novel capillary electrophoresis (CE) with chemiluminescence (CL) detection
      method for the determination of mitoxantrone (MTX) has been developed, which
      based on the CL reaction of potassium ferricyanide with luminol in sodium
      hydroxide medium sensitized by MTX. Under optimum analytical conditions, MTX is
      determined over the range of 7.0*10(-8)-1.0*10(-6)M with a detection limit of
      1.0*10(-8)M. The relative standard deviation (RSD) was 3.7%, 2.6% and 3.0% for
      7.0*10(-8), 5.0*10(-7) and 1.0*10(-6)M MTX (n=11), respectively. In laboratory
      built CE-CL apparatus, the proposed method has been applied to determination of
      MTX in commercial drug and spiked in human urine and plasma with satisfactory
      results.

PMID- 20817571
TI  - Basophils orchestrate chronic allergic dermatitis and protective immunity against
      helminths.
AB  - Basophils are associated with T helper 2 (Th2) cell-polarized immune responses
      such as allergic disorders or helminth infections. To directly address the role
      of basophils for type 2 immunity, we generated transgenic mice with constitutive
      and selective deletion of basophils. Differentiation and accumulation of Th2
      cells, induction of eosinophilia, and increase in serum IgE or IgG1 induced by
      allergens or by infection with the helminth Nippostrongylus brasiliensis appeared
      to be basophil independent. Further, basophils were not required for passive IgE-
      or IgG1-mediated systemic anaphylaxis. However, basophils were essential for IgE
      meditated chronic allergic dermatitis and for protection against secondary
      infection with N. brasiliensis. These results demonstrate that basophils play an
      important role for protective immunity against helminths and orchestrate chronic
      allergic inflammation, whereas primary Th2 cell responses can operate efficiently
      in the absence of this cell type.

PMID- 20817573
TI  - Lateral chest radiograph a systematic approach.
AB  - The lateral chest radiograph is a valuable source of information that has become
      increasingly undervalued in the era of chest computed tomography. Optimal use of
      the lateral radiograph requires systematic analysis. First is an overview,
      followed by analysis of the airway and major hilar structures. Next is attention
      to the three areas where the image darkens in the absence of visible structure
      edges. Last is attention to the periphery and the upper abdomen. This
      communication outlines the systematic analysis and then explains in more detail
      the value of the critical features of that analysis.

PMID- 20817572
TI  - Response assessment in patients with multiple myeloma during antiangiogenic
      therapy using arterial spin labeling and diffusion-weighted imaging: a
      feasibility study.
AB  - RATIONALE AND OBJECTIVES: To determine whether response to anti-angiogenic
      therapy in patients with multiple myeloma can be assessed by noncontrast
      perfusion magnetic resonance imaging (MRI) (ie, arterial-spin-labeling [ASL]),
      and diffusion-weighted [DWI] MRI. MATERIALS AND METHODS: The study protocol was
      approved by the local institutional ethic board. Ten consecutive patients (eight
      men, two women; mean age 60.5 +/- 8.5 years) with Stage III multiple myeloma were
      prospectively included. MRI was performed at baseline, as well as 3 and 8 weeks
      after onset of antiangiogenic therapy. Functional MRI data were compared with
      clinical outcome and conventional lesion size and signal-intensity measurements.
      Differences between baseline and follow-up values for ASL-MRI and DWI-MRI were
      assessed using a paired Student t-test. RESULTS: Nine patients responded well to
      therapy, whereas one patient was classified a nonresponder. Temporary changes in
      signal intensity between baseline and follow-up examinations were inconsistent on
      T1-weighted (w) and T2w images. Likewise, determination of lesion size at follow
      up proved unreliable. ASL showed a marked decrease in perfusion from baseline
      (251 +/- 159 mL/(min*100g)) to follow-up at 3 weeks (115 +/- 85 mL/(min*100g), P
      = .01) and 8 weeks (101 +/- 90 mL/(min*100g, P = .01), respectively. Relative to
      the baseline examination, mean diffusion increased from 0.68 +/- 0.19 * 10(-3)
      s/mm(2) at baseline to 0.94 +/- 0.24 * 10(-3) s/mm(2) after 3 weeks (P = .04),
      and 0.96 +/- 0.40 * 10(-3) s/mm(2) after 8 weeks (P = .049). Both methods were
      able to correctly classify 9/10 patients as responder or nonresponder.
      CONCLUSION: ASL perfusion as well as DWI-MRI provide accurate, clinically
      relevant information regarding tumor viability and can predict response already
      early after therapy onset, as opposed to classical lesion size and MRI signal
      intensity measurements.

PMID- 20817574
TI  - Multimodality non-rigid image registration for planning, targeting and monitoring
      during CT-guided percutaneous liver tumor cryoablation.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to develop non-rigid image
      registration between preprocedure contrast-enhanced magnetic resonance (MR)
      images and intraprocedure unenhanced computed tomographic (CT) images, to enhance
      tumor visualization and localization during CT imaging-guided liver tumor
      cryoablation procedures. MATERIALS AND METHODS: A non-rigid registration
      technique was evaluated with different preprocessing steps and algorithm
      parameters and compared to a standard rigid registration approach. The Dice
      similarity coefficient, target registration error, 95th-percentile Hausdorff
      distance, and total registration time (minutes) were compared using a two-sided
      Student's t test. The entire registration method was then applied during five CT
      imaging-guided liver cryoablation cases with the intraprocedural CT data
      transmitted directly from the CT scanner, with both accuracy and registration
      time evaluated. RESULTS: Selected optimal parameters for registration were a
      section thickness of 5 mm, cropping the field of view to 66% of its original
      size, manual segmentation of the liver, B-spline control grid of 5 * 5 * 5, and
      spatial sampling of 50,000 pixels. A mean 95th-percentile Hausdorff distance of
      3.3 mm (a 2.5 times improvement compared to rigid registration, P < .05), a mean
      Dice similarity coefficient of 0.97 (a 13% increase), and a mean target
      registration error of 4.1 mm (a 2.7 times reduction) were measured. During the
      cryoablation procedure, registration between the preprocedure MR and the planning
      intraprocedure CT imaging took a mean time of 10.6 minutes, MR to targeting CT
      image took 4 minutes, and MR to monitoring CT imaging took 4.3 minutes. Mean
      registration accuracy was <3.4 mm. CONCLUSIONS: Non-rigid registration allowed
      improved visualization of the tumor during interventional planning, targeting,
      and evaluation of tumor coverage by the ice ball. Future work is focused on
      reducing segmentation time to make the method more clinically acceptable.

PMID- 20817575
TI  - Hybrid segmentation of mass in mammograms using template matching and dynamic
      programming.
AB  - RATIONALE AND OBJECTIVES: Accurate image segmentation for breast lesions is a
      critical step in computer-aided diagnosis systems. The objective of this study
      was to develop a robust method for the automatic segmentation of breast masses on
      mammograms to extract feasible features for computer-aided diagnosis systems.
      MATERIALS AND METHODS: The data set used in this study consisted of 483 regions
      of interest extracted from 328 patients. A hybrid method for segmenting breast
      masses was proposed on the basis of the template-matching and dynamic programming
      techniques. First, a template-matching technique was used to locate and obtain
      the rough region of masses. Then, on the basis of this rough region, a local cost
      function for dynamic programming was defined. Finally, the optimal contour was
      derived by applying dynamic programming as an optimization technique. The
      performance of this proposed segmentation method was evaluated using area-based
      and boundary distance-based similarity measures based on radiologists' manually
      marked annotations. A comparison with three different segmentation algorithms on
      the data set was provided. RESULTS: The mean overlap percentage for our proposed
      hybrid method was 0.727 +/- 0.127, whereas those for Timp and Karssemeijer's
      dynamic programming method, Song et al's plane-fitting and dynamic programming
      method, and the normalized cut segmentation method were 0.657 +/- 0.216, 0.636 +/
      0.190, and 0.562 +/- 0.199, respectively. All P values for the measure
      distribution of our proposed method and the other three algorithms were <.001.
      CONCLUSIONS: A hybrid method based on the template-matching and dynamic
      programming techniques was proposed to segment breast masses on mammograms.
      Evaluation results indicate that the proposed segmentation method can improve the
      accuracy of mass segmentation compared to three other algorithms. The proposed
      segmentation method shows better performance and has great potential in improving
      the accuracy of computer-aided diagnosis systems in interpreting mammograms.

PMID- 20817576
TI  - Ovarian fibromas in pediatric patients with basal cell nevus (Gorlin) syndrome.
AB  - BACKGROUND: Gorlin syndrome is a rare genetic condition consisting of multiple
      basal cell nevi associated with other entities such as medulloblastoma, skeletal
      abnormalities, and ovarian fibromas. CASE: A 15-year-old girl presented with
      abdominal discomfort. Magnetic resonance imaging showed multiple bilateral solid
      adnexal masses, the largest measuring 5.5 cm * 6.1 cm * 5.6 cm. At laparoscopy,
      10 ovarian fibromas, ranging from 3 mm to 7 cm in size, were removed from each
      ovary. Concurrent with her gynecologic course, she was found to have maxillary
      sinus cysts and multiple basal cell nevi. The patient's history was also
      significant for a medulloblastoma as an infant. Given this constellation of
      findings, a diagnosis of Gorlin syndrome was made. CONCLUSION: The development of
      ovarian fibromas in the pediatric population is rare. When diagnosed, the
      possibility of Gorlin syndrome must be considered. Furthermore, females with
      Gorlin syndrome would benefit from regular gynecologic surveillance.

PMID- 20817577
TI  - Seizures and intellectual outcome: clinico-radiological study of 30 Egyptian
      cases of tuberous sclerosis complex.
AB  - BACKGROUND AND OBJECTIVES: Tuberous sclerosis complex (TSC) is a multi-systemic
      disorder that involves primarily CNS, skin, kidney and heart. The aim of this
      study is to determine whether seizures type, interictal EEGs and tubers burden in
      MRI are correlated to seizure and intellectual outcome, and to identify the
      clinical risk factors for mental retardation and developing autism in these
      patients. METHODS: This was a prospective study that was conducted on 30 Egyptian
      children with tuberous sclerosis complex (TSC), diagnosed according to the
      criteria of National Institutes of Health consensus conference revised the
      diagnostic criteria for TSC. All patients underwent clinical and psychometric
      evaluation, interictal EEG, and MRI brain. RESULTS AND CONCLUSIONS: We found that
      poor intellectual outcome is related to early onset of seizures, infantile
      spasms, severely epileptogenic EEG findings and tuber burden on the Left side.
      Autistic behavior is related to seizure type (more with infantile spasms),
      severely epileptogenic EEG findings, frontal location of tubers and higher number
      of tubers (>8).

PMID- 20817578
TI  - Transdural motor cortex stimulation reverses neuropathic pain in rats: a profile
      of neuronal activation.
AB  - Motor cortex stimulation (MCS) has been used to treat patients with neuropathic
      pain resistant to other therapeutic approaches; however, the mechanisms of pain
      control by MCS are still not clearly understood. We have demonstrated that MCS
      increases the nociceptive threshold of naive conscious rats, with opioid
      participation. In the present study, the effect of transdural MCS on neuropathic
      pain in rats subjected to chronic constriction injury of the sciatic nerve was
      investigated. In addition, the pattern of neuronal activation, evaluated by Fos
      and Zif268 immunolabel, was performed in the spinal cord and brain sites
      associated with the modulation of persistent pain. MCS reversed the mechanical
      hyperalgesia and allodynia induced by peripheral neuropathy. After stimulation,
      Fos immunoreactivity (Fos-IR) decreased in the dorsal horn of the spinal cord and
      in the ventral posterior lateral and medial nuclei of the thalamus, when compared
      to animals with neuropathic pain. Furthermore, the MCS increased the Fos-IR in
      the periaqueductal gray, the anterior cingulate cortex and the central and
      basolateral amygdaloid nuclei. Zif268 results were similar to those obtained for
      Fos, although no changes were observed for Zif268 in the anterior cingulate
      cortex and the central amygdaloid nucleus after MCS. The present findings suggest
      that MCS reverts neuropathic pain phenomena in rats, mimicking the effect
      observed in humans, through activation of the limbic and descending pain
      inhibitory systems. Further investigation of the mechanisms involved in this
      effect may contribute to the improvement of the clinical treatment of persistent
      pain.

PMID- 20817579
TI  - Interobserver agreement in describing video capsule endoscopy findings: a
      multicentre prospective study.
AB  - BACKGROUND AND AIM: Few studies have specifically addressed interobserver
      agreement in describing lesions identified during capsule endoscopy. The aim of
      our study is to evaluate interobserver agreement in the description of capsule
      endoscopy findings. MATERIALS AND METHODS: Consecutive short segments of capsule
      endoscopy were prospectively observed by 8 investigators. Seventy-five videos
      were prepared by an external investigator (gold standard). The description of the
      findings was reported by the investigators using the same validated and
      standardized capsule endoscopy structured terminology. The agreement was assessed
      using Cohen's kappa statistic. RESULTS: As concerns the ability to detect a
      lesion, the agreement with the gold standard was moderate (kappa 0.48), as well
      as the agreement relating to the final diagnosis (kappa 0.45). The best agreement
      was observed in identifying the presence of active bleeding (kappa 0.72), whereas
      the poorest agreement concerned the lesion size (kappa 0.32). The agreement with
      the GS was significantly better in endoscopists with higher case/volume of
      capsule endoscopy per year. Diagnostic concordance was better in the presence of
      angiectasia than in the presence of polyps or ulcers/erosions. CONCLUSIONS:
      Correct lesion identification and diagnosis seem more likely to occur in presence
      of angiectasia, and for readers with more experience in capsule endoscopy
      reading.

PMID- 20817580
TI  - [Therapeutic approach in a giant cystic prolactinoma].

PMID- 20817581
TI  - [Prematurity with cerebral palsy and ceroid lipofuscinosis].

PMID- 20817582
TI  - [Gastrointestinal disorders in children with cerebral palsy and
      neurodevelopmental disabilities].
AB  - Recent data suggest that, contrary to initial expectations with improvements in
      perinatal medicine, the prevalence of cerebral palsy has not decreased over the
      last 20 years. Gastrointestinal disorders are a major chronic problem in most of
      children with cerebral palsy and in children with neurodevelopmental
      disabilities. A multidisciplinary approach, with input from neurologists,
      gastroenterologists, nurses, dieticians and other specialists, can make a major
      contribution to the medical wellbeing and quality of life of these children and
      their caregivers. This article focuses on diagnostic methods and therapeutic
      options available for major nutritional and gastrointestinal problems in patients
      with neurological disabilities: gastroesophageal reflux, constipation and
      swallowing disorders.

PMID- 20817583
TI  - [Neuroblastoma staging: discrepancies between 18F-FDG-PET and 123I-MIBG].

PMID- 20817584
TI  - Detection of bacterial and viral organisms from the conjunctiva of cats with
      conjunctivitis and upper respiratory tract disease.
AB  - A variety of pathogens are involved in conjunctivitis in cats. In this study, the
      prevalence of feline herpesvirus (FHV), Chlamydophila felis, mycoplasmas, and
      aerobic bacteria on the conjunctival surface of cats with conjunctivitis and
      upper respiratory tract disease was investigated by polymerase chain reaction
      (PCR), immunofluorescent assay (IFA), and aerobic bacterial culture of ocular
      swabs. Forty-one cats were included of which 37 were found to be infected with an
      ocular organism. Single and multiple infections were present in 15 and 22 cats,
      respectively. FHV, mycoplasmas, and C felis were detected by PCR in 11 (27%), 20
      (49%), and 23 (56%) cats, respectively. IFA detected 10 cats as positive for C
      felis. Mycoplasma felis, Mycoplasma canadense, Mycoplasma cynos, Mycoplasma
      gateae, Mycoplasma lipophilum, and Mycoplasma hyopharyngis were identified by
      genetic sequencing. The most common aerobic bacteria cultured included
      Staphylococcus species, Streptococcus species and Micrococcus species. The
      prevalence of mycoplasmas in cats with conjunctivitis was higher than previously
      reported, and four of the Mycoplasma species have not been described in cats so
      far.

PMID- 20817585
TI  - Effects of metoclopramide on emesis in cats sedated with xylazine hydrochloride.
AB  - The prophylactic anti-emetic effect of five dosages of metoclopramide (0.2, 0.4,
      0.6, 0.8 and 1mg/kg, IM) was evaluated against saline solution, both injected 1h
      before administration of xylazine in cats. Saline was administered to cats (day
      0) followed by sequentially increasing dosages of metoclopramide at 1-week
      intervals. After xylazine injection, all cats were carefully observed to record
      the frequency of emesis and the time until onset of the first emetic episode. The
      onset of sedation in these cats was also studied. Prior treatment with each
      dosage of metoclopramide significantly reduced the frequency of emetic episodes
      (P<0.05). Metoclopramide administration prior to xylazine injection did not alter
      the time until onset of the first emetic episode at any of mentioned dosages, but
      significantly reduced the time until onset of sedation only at the dose of
      1mg/kg. Metoclopramide may be used as a prophylactic anti-emetic in cats sedated
      with xylazine hydrochloride.

PMID- 20817586
TI  - Progesterone intoxication inducing marked sedation in a cat.
AB  - A 3-year-old, male castrated domestic shorthair cat presented for sudden onset of
      severe lethargy and loss of balance a few hours after potentially ingesting
      capsules containing progesterone. Elevated serum progesterone was confirmed.
      Supportive care and time resulted in complete resolution of the clinical signs
      with no long-term complications or recurrence of clinical signs noticed after 1
      month follow-up. This is the first description of progesterone intoxication
      inducing neurological signs in a cat.

PMID- 20817587
TI  - Bartonella species, feline herpesvirus-1, and Toxoplasma gondii PCR assay results
      from blood and aqueous humor samples from 104 cats with naturally occurring
      endogenous uveitis.
AB  - Toxoplasma gondii, Bartonella henselae and feline herpesvirus-1 (FHV-1) have been
      implicated as causative agents in feline uveitis. The usefulness of serum and
      aqueous humor (AH) antibody testing for these agents is limited as antibodies can
      be detected in both healthy cats and cats with uveitis. Very few studies using
      polymerase chain reaction (PCR) assays to amplify organism DNA from samples from
      cats with uveitis have been performed. In this study, assays to detect T gondii
      antibodies, feline leukemia virus antigen, feline immunodeficiency virus
      antibody, and Bartonella species antibodies were performed on serum and PCR
      assays for amplification of T gondii, Bartonella species, and FHV-1 DNA were
      performed on blood and AH samples from 104 cats with endogenous uveitis and 19
      healthy cats. Results suggest the addition of the PCR assay to the diagnostic
      work-up for cats with uveitis will increase the detection of T gondii and FHV-1;
      however, the diagnostic usefulness of these additional data is not clear.

PMID- 20817588
TI  - Naturally occurring Tritrichomonas foetus infections in Australian cats: 38
      cases.
AB  - A total of 38 cases of naturally occurring intestinal tritrichomoniasis in
      Australian cats are described. Detailed information was available for 13 cases
      diagnosed in two veterinary hospitals, one in Victoria and one in New South Wales
      (NSW). In all instances, presumptive microscopic diagnoses were confirmed by
      polymerase chain reaction (PCR) testing. Affected cats were generally young
      (median age 8 months) and of a pedigree breed (12/13 cats; 92%). Diarrhoea was
      observed in 10 cats (77%); the remaining three cats were asymptomatic and
      detected by screening undertaken because these cats cohabited with symptomatic
      cases. Concurrent infections with Giardia species (7/13 cats; 54%), and Toxocara
      species and Eucoleus species (2/13 cats; 15%) were identified. Treatment of
      tritrichomoniasis with ronidazole at a dose of 30mg/kg once or twice a day, in
      concert with appropriate therapy of concurrent gastrointestinal infections,
      resolved diarrhoea in all cats treated. Limited case details of a further 25
      infected cats were obtained from a commercial laboratory offering a real-time PCR
      assay for Tritrichomonas foetus, and compared with findings from the 13 cats
      presenting to the contributing veterinary hospitals. All samples submitted to
      this laboratory returning a positive PCR result were from pedigree cats
      maintained in multi-cat facilities. Most of the samples were derived from
      Victoria (4/8 catteries tested; 50%), although positive samples were also
      identified from cats in NSW (1/4 catteries tested; 25%), Queensland (1/4
      catteries; 25%), Tasmania (1/4 catteries; 25%) and South Australia (1/4
      catteries; 25%). Our impression is that intestinal tritrichomoniasis is an
      emerging infectious disease of Australian cats. Tests to detect T foetus should
      be a routine component of the work-up of chronic diarrhoea in cats, especially
      young purebred cats.

PMID- 20817589
TI  - Comment on "Pediatric disease burden and vaccination recommendations:
      understanding local differences.".

PMID- 20817590
TI  - Analysis of the sarcomere protein gene mutation on cardiomyopathy - Mutations in
      the cardiac troponin I gene.
AB  - Developments in the molecular genetic studies of cardiomyopathy (CM) have led to
      discovery of a large number of mutations in the genes encoding the sarcomeric
      proteins. In this study, comprehensive screening of TNNI3 was performed in 36
      consented autopsy cases diagnosed as CM, in order to evaluate the prevalence of
      gene mutations in sudden death caused by CM. In DCM cases, a new missense
      mutation Pro16Thr was detected. A single nucleotide polymorphism at -8 position
      of intron 3 (IVS 3 -8 T>A) was identified, which had a significant difference in
      allele frequency between DCM and control cases. From these results, it was
      indicated that this study contribute to genetic based diagnosis, risk
      stratification and prevention of sudden death caused by CM.

PMID- 20817591
TI  - Attitudes regarding reporting healthcare-associated patient deaths to the police:
      A nationwide survey of physicians and RMs in Japanese teaching hospitals.
AB  - In Japan, healthcare professionals are required by Article 21 of the Medical
      Practitioner's Law to report "unnatural deaths" to the police in cases of
      healthcare-associated patient death. The attitudes of medical personnel at the
      forefront of clinical medicine regarding reporting have not been described. We
      investigate the attitudes of physicians and risk managers (RMs) regarding
      reporting to the police under different circumstances. We sent standardized
      questionnaires to all hospitals in Japan that participate in the National General
      Residency Program. We asked physicians and RMs to indicate if they would report
      to the police or not under scenarios including cases where medical error is
      present, uncertain, or absent. We also asked if they would report when medical
      error had occurred and the cause-of-death was directly related, possibly related,
      or unrelated. We found most physicians believe they would report to the police if
      medical error clearly caused patient death. We found most RMs believe they would
      advise physicians to report given the same situation. Less but still a large
      number of participants favor reporting even when cause-of-death is not clearly
      related to medical care provided. This tendency persisted even when given a
      scenario where the hospital director opposed the decision to report.

PMID- 20817592
TI  - Born to choose: the origins and value of the need for control.
AB  - Belief in one's ability to exert control over the environment and to produce
      desired results is essential for an individual's wellbeing. It has repeatedly
      been argued that perception of control is not only desirable, but is also
      probably a psychological and biological necessity. In this article, we review the
      literature supporting this claim and present evidence of a biological basis for
      the need for control and for choice-that is, the means by which we exercise
      control over the environment. Converging evidence from animal research, clinical
      studies and neuroimaging suggests that the need for control is a biological
      imperative for survival, and a corticostriatal network is implicated as the
      neural substrate of this adaptive behavior.

PMID- 20817593
TI  - Structural properties of molybdenum-lead-borate glasses.
AB  - Glasses and glass ceramics in the system xMoO3.(100 - x)[3B2O3.PbO] with 0 <= x
      <= 30 mol% have been prepared from melt quenching method and characterized by
      means of X-ray diffraction, FTIR, UV-VIS and EPR spectroscopy. We have examined
      and analyzed the effects of systematic molybdenum ions intercalation on lead
      borate glasses and glass ceramics with interesting results. The observations
      present in these mechanisms show the lead ions bonded ionic have a strong
      affinity towards [BO3] units containing non-bridging oxygens and [MoO4]2-
      molybdate units. The pronounced affinity towards molybdate anions yields the
      formation of the PbMoO4 crystalline phase. Then, the excess of oxygen can be
      supported into the glass network by the formation of [MoO6] and [Mo2O7]
      structural units. Pb2(+) ions with 6s2 configuration show strong absorption in
      the ultraviolet due to parity allowed s2-sp transition and yield an absorption
      band centered at about 310 nm. The changes in the features of the absorption
      bands centered at about 310 nm can be explained as a consequence of the
      appearance of additional absorption shoulder due to photoinduced color centers in
      the glass such as the formation of borate-molybdate and lead-molybdate
      paramagnetic defect centers in the glasses. The concentration of molybdenum ions
      influences the shape and width of the EPR signals located at g ~ 1.86, 1.91 and
      5.19. The microenvironment of molybdenum ions in glasses is expected to have
      mainly sixfold coordination. However, there is a possibility of reduction of a
      part of molybdenum ions from the Mo6(+) to the Mo5(+) and Mo4(+) to the Mo3(+)
      states.

PMID- 20817594
TI  - Evaluation of white-rot fungi-assisted alkaline/oxidative pretreatment of corn
      straw undergoing enzymatic hydrolysis by cellulase.
AB  - In this study, the effects of biological treatment prior to alkaline/oxidative
      (A/O) pretreatment using three white-rot fungi (Ganoderma lucidum, Trametes
      versicolor and Echinodontium taxodii) were evaluated for the enzymatic hydrolysis
      of corn straw. Among these fungi, Echinodontium taxodii significantly enhanced
      the efficiency of chemical pretreatment. Subsequent to treatment of corn straw
      with Echinodontium taxodii for 15 days, the straw was subjected to digestion by
      0.0016% NaOH and 3% H2O2 at room temperature for 24 h, which increased the
      reducing sugar yield by 50.7%. The hydrolysis model and kinetic parameters were
      determined from time course data collected throughout the hydrolysis. The initial
      hydrolysis rate, V0, of the corn straw increased by 68.5% compared to A/O
      pretreatment alone, which resulted from an increase in the initial adsorption.
      The lignin content of the corn straw decreased more significantly after
      biological and A/O pretreatment than after A/O pretreatment alone. After 72 h of
      enzymatic hydrolysis, the adsorbed cellulase decreased by 24.8% (from 3.67 to
      2.76 mg ml-1) compared to A/O pretreatment alone. These results indicate that
      biological treatment improves the desorption of cellulase by enhancing
      delignification during A/O pretreatment.

PMID- 20817595
TI  - Restless legs syndrome: understanding its consequences and the need for better
      treatment.
AB  - Restless legs syndrome (RLS) is a very common neurologic disorder with a
      prevalence of disease resulting in moderate and severe health impact of at least
      2.7%. The purpose of this review, commissioned by the International Restless Legs
      Syndrome Study Group, was to assess the medical literature on the consequences of
      RLS and the limitations of existing therapies. We conclude that RLS affects
      quality of life at least as severely as other common chronic illnesses and in
      particular results in insomnia, anxiety and depression. Epidemiologic evidence
      suggests a relationship between RLS and cardiovascular disease. Dopaminergic
      medications are effective but their use is limited by adverse effects, especially
      augmentation and impulse control disorders. Other classes of medications have
      variable effectiveness, undesirable side effects and few large controlled trials.
      We recommend increased commitment to funding RLS research in both the
      pathophysiology of the disorder and its treatment. Future therapeutic trials for
      RLS should include measures of quality of life, mood and sleep. Drug regulatory
      agencies are urged to consider the prevalence and impact of RLS as well as the
      limitations of existing therapies in determining the risk-benefit ratio of new
      drugs submitted for possible approval.

PMID- 20817596
TI  - Improved computation of the atonia index in normal controls and patients with REM
      sleep behavior disorder.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of a simple method
      of noise reduction before the calculation of the REM sleep atonia index (AI) on a
      large number of recordings from different normal controls and patient groups.
      SUBJECTS AND METHODS: Eighty-nine subjects were included: 25 young controls, 10
      aged controls, 31 untreated patients with idiopathic REM sleep behavior disorder
      (iRBD), 8 treated patients with iRBD, 10 patients with multiple system atrophy
      (MSA) and 5 patients with obstructive sleep apnea syndrome (OSAS). The average
      amplitude of the rectified submentalis muscle EMG signal was then obtained for
      all 1-s mini epochs of REM sleep. The new correction method was implemented by
      subtracting from each mini epoch the minimum value found in a moving window
      including the 60 mini epochs surrounding it. RESULTS: Two arbitrary thresholds
      were established at AI<0.8 and 0.8<AI<0.9; all young controls presented AI>0.9;
      this was not true for aged controls, 3 of whom presented 0.8<AI<0.9 but none had
      AI<0.8; on the contrary 74.4% of all iRBD showed AI<0.9, with 38.5% of the whole
      group having AI<0.8 and only 25.6% with AI>0.9. All MSA patients showed AI<0.8.
      CONCLUSIONS: After the introduction of this new method for noise reduction, REM
      sleep AI index values lower than 0.8 were strongly indicative of altered
      (reduced) chin EMG atonia during REM sleep; values of AI between 0.8 and 0.9
      indicated a less evident involvement of atonia, and values above 0.9
      characterized the majority of normal recordings.

PMID- 20817597
TI  - Effect of tetrabenazine use on restless legs syndrome.

PMID- 20817598
TI  - Efficacy and safety of doxepin 6 mg in a model of transient insomnia.
AB  - INTRODUCTION: The efficacy and safety of doxepin (DXP) 6mg tablets were evaluated
      in healthy adults in a model of transient insomnia. METHODS: This was a
      randomized, double-blind, parallel-group, placebo-controlled study in healthy
      adults using a model of transient insomnia. A first-night effect combined with a
      3-h phase advance was implemented to induce transient insomnia in healthy adults.
      Subjects received a single night time dose of placebo (PBO; N=282) or DXP 6mg
      (N=283) in a sleep laboratory. Efficacy was evaluated objectively
      (polysomnography; PSG) and subjectively (morning questionnaire). Consistent with
      the model utilized, the primary endpoint was latency to persistent sleep (LPS);
      secondary PSG endpoints included wake after sleep onset (WASO; key secondary
      endpoint), total sleep time (TST), wake time after sleep (WTAS) and sleep
      efficiency (SE; overall, by quarter of the night and hourly); secondary
      subjective endpoints included latency to sleep onset (LSO), subjective WASO
      (sWASO), subjective TST (sTST) and sleep quality. RESULTS: DXP 6mg demonstrated
      statistically significant improvements in LPS (13min decrease versus PBO;
      p<0.0001), WASO (39min less than PBO; p<0.0001), TST (51min more than PBO;
      p<0.0001), WTAS (p<0.0001), overall SE (p<0.0001), SE in each quarter of the
      night (p<0.0001) and SE in each of the 8h (p?0.0003), all versus PBO.
      Additionally, DXP 6mg significantly improved subjective variables including LSO
      (p<0.0001), sWASO (p=0.0063), sTST (p<0.0001), and sleep quality (p=0.0004),
      versus PBO. There was no consistent evidence of next-day residual sedation and
      also minor sleep stages alterations. The incidence of adverse events was
      comparable to placebo. CONCLUSIONS: In this model of transient insomnia, DXP 6mg
      demonstrated significant improvements in sleep onset, sleep maintenance, sleep
      duration and sleep quality, and also appeared to reduce early morning awakenings.
      These data suggest that DXP 6mg may be effective and well tolerated in adults
      experiencing transient insomnia.

PMID- 20817599
TI  - Complaints of insomnia among midlife employed people: the contribution of
      childhood and present socioeconomic circumstances.
AB  - BACKGROUND: Studies using conventional socioeconomic indicators have reported
      inconsistent evidence on socioeconomic differences in complaints of insomnia. We
      lack studies using a comprehensive socioeconomic framework over the life course
      ranging from childhood to adulthood. This study therefore aimed to examine the
      associations of both past and present socioeconomic circumstances with complaints
      of insomnia. METHODS: Data were derived from cross-sectional postal surveys (2000
      2002) representative of the staff of the City of Helsinki, Finland (n=8960, aged
      40-60 years). Socioeconomic circumstances were measured by parental education,
      childhood economic difficulties, own education, occupational class, household
      income, housing tenure, and current economic difficulties. Complaints of insomnia
      during the previous month were measured by difficulties initiating and
      maintaining sleep and non-restorative sleep. Logistic regression analysis was
      used, adjusting for age and marital status. RESULTS: Complaints of insomnia at
      least once a week were reported by 25% of women and 21% of men. Childhood
      economic difficulties showed associations with complaints of insomnia among both
      women (OR 1.52; 95% CI 1.31-1.76) and men (OR 2.25; 95% CI 1.67-3.02) even after
      full adjustments. Also current economic difficulties remained associated with
      complaints of insomnia, but only among women (OR 1.65; 95% CI 1.41-1.93).
      However, education, occupational class, and income showed only limited age
      adjusted associations with complaints of insomnia and these associations
      disappeared after full adjustments. DISCUSSION: Past and present economic
      difficulties were strongly associated with current complaints of insomnia.
      Supporting both families with children and adults to cope with their economic
      difficulties might reduce complaints of insomnia in adulthood.

PMID- 20817600
TI  - Comparative levels of excessive daytime sleepiness in common medical disorders.
AB  - INTRODUCTION: Sleep restriction and sleep disorders are common causes of
      excessive daytime sleepiness (EDS). Medical disorders (MD) can also cause EDS,
      but previous studies have used non-standardized measures, selected samples, or
      have examined EDS in singular disorders. This study describes the relative degree
      of EDS associated with medical disorders to provide comparative data across a
      range of common medical conditions in a large unselected community-based sample.
      METHODS: Responses of 2612 individuals (aged 18-65) were assessed after excluding
      those with suspected sleep disordered breathing, narcolepsy, and shift workers.
      Participants across a range of medical disorders were evaluated using the Epworth
      Sleepiness Scale (ESS) and patient reports of nocturnal sleep. RESULTS: Sixty
      seven percent of the sample reported a MD. The prevalence of EDS (ESS>or=10) was
      31.4% in individuals with MD and increased as a function of a number of MD (0
      MD=29.4%, 1 MD=28.4%, 2 MD=31.0%, 3 MD=35.3%, 4 MD=38.4%). Disorders which were
      independent predictors of EDS were ulcers OR=2.21 (95% CI=1.35-3.61), migraines
      OR=1.36 (95% CI=1.08-1.72), and depression OR=1.46 (95% CI=1.16-1.83) after
      controlling for other conditions, age, gender, time in bed, caffeine, smoking and
      alcohol use. Participants with ulcers had the highest prevalence of sleepiness,
      50.0%, as well as the highest level of problems falling asleep (40.8%) and
      awakenings during the night (62.5%). CONCLUSIONS: Individuals with ulcers,
      migraines, and depression have independent and clinically significant levels of
      EDS relative to other common MD.

PMID- 20817601
TI  - Sleep syncope: important clinical associations with phobia and vagotonia.
AB  - OBJECTIVES: To compare demographic and clinical data from patients with sleep
      syncope to those of patients with "classical" vasovagal syncope [VVS] collected
      over the last 8 years. DESIGN: Retrospective case-controlled study. SETTING:
      Syncope unit. PATIENTS AND METHODS: Fifty-four patients with a history suggestive
      of one or more episodes of sleep syncope (group SS) were matched for age and
      gender to 108 patients with VVS (control group). A syncope questionnaire was
      completed immediately before tilt-testing and included frequency, age-of-onset
      and severity of episodes; situations, postures and perceived triggers; lifetime
      prevalence of specific phobias; and symptoms during syncope. RESULTS: Group SS
      were mainly women (65%), mean age of 46+/-2.1 years, with a mean lifetime total
      of 5.4+/-0.83 episodes of sleep syncope. Compared to controls, SS episodes were
      more likely to start in childhood, 26.9% versus 50% (p=0.005), and more severe,
      score 2.40+/-0.11 versus 2.81+/-0.15 (p=0.03). In group SS: syncope onset whilst
      lying down was more frequent, 4.6% versus 32.7% (p=0.001); the lifelong
      prevalence of any specific phobia was higher, 32.4% versus 74.5% (p=0.001), in
      particular blood injection injury (BII) phobia, 19.4% versus 57.4% (p=0.001); and
      during attacks, distressing vagal symptoms were more frequent, e.g., abdominal
      discomfort, 13.9% versus 72.2% (p=0.001). CONCLUSION: Sleep syncope is not rare
      and is characterised by lifelong, intermittent but severe episodes of vasovagal
      syncope which may occur in the horizontal position, with distressing abdominal
      symptoms. BII phobia is strongly associated and may be a predisposing factor or a
      co-existent disorder in these patients.

PMID- 20817602
TI  - Loss of response during long-term treatment of restless legs syndrome: guidelines
      approved by the International Restless Legs Syndrome Study Group for use in
      clinical trials.

PMID- 20817604
TI  - Obstructive sleep apnoea syndrome: "through the looking glass" of transcranial
      magnetic stimulation.

PMID- 20817603
TI  - Insomnia and the risk for suicide: does sleep medicine have interventions that
      can make a difference?

PMID- 20817605
TI  - Inflammatory signaling pathways in self-renewing breast cancer stem cells.
AB  - Cancer stem cells (CSCs), which make up only a small proportion of heterogeneous
      tumor cells, may possess greater ability to maintain tumorigenesis than do other
      tumor cell types. Breast cancer tissue is reported to contain cancer stem-like
      cells. In order to eradicate tumor cells, various approaches have been taken to
      identify the critical molecules and signaling pathways in breast CSCs. Recent
      findings suggest that inflammatory signaling pathways are important for the
      maintenance of breast CSCs. Here, we review the current understanding of the role
      of inflammatory pathways in these cells and discuss future perspectives of the
      research on and the possibility of targeting the molecules involved in these
      pathways for developing treatments for breast cancer.

PMID- 20817606
TI  - Convergent integration of animal model and human studies of bipolar disorder
      (manic-depressive illness).
AB  - Animal models and human studies of bipolar disorder and other psychiatric
      disorders are becoming increasingly integrated, prompted by recent successes.
      Particularly for genomics, the convergence and integration of data across
      species, experimental modalities and technical platforms is providing a fit-to
      disease way of extracting reproducible and biologically important signal, in
      sharp contrast to the fit-to-cohort effect, disappointing findings to date, and
      limited reproducibility of human genetic analyses alone. Such work in psychiatry
      can provide an example of how to address other genetically complex disorders, and
      in turn will benefit by incorporating concepts from other areas, such as cancer
      biology and diabetes.

PMID- 20817608
TI  - APOE and cholesterol homeostasis in Alzheimer's disease.
AB  - Converging evidence from clinical and pathological studies indicate the presence
      of important relationships between the ongoing deterioration of brain lipid
      homeostasis, vascular changes and the pathophysiology of sporadic Alzheimer's
      disease (AD). These associations include the recognition of cholesterol
      transporters apolipoprotein E (APOE), APOC1 and APOJ as major genetic risk
      factors for common AD and observations associating risk factors for
      cardiovascular disease such as high midlife plasma cholesterol, diabetes, stroke,
      obesity and hypertension to dementia. Moreover, recent clinical findings lend
      support to the notion that progressive deterioration of cholesterol homeostasis
      in AD is a central player in the disease pathophysiology and is, therefore, a
      potential therapeutic target for disease prevention.

PMID- 20817607
TI  - Insulin signaling in fatty acid and fat synthesis: a transcriptional perspective.
AB  - Transcription of enzymes involved in FA and TAG synthesis is coordinately induced
      in lipogenic tissues by feeding and insulin treatment. The three major
      transcription factors involved are USF, SREBP-1c, and LXRalpha. New insights into
      the insulin-signaling pathway(s) that control(s) lipogenic gene transcription via
      these factors have recently been revealed. Dephosphorylation/activation of DNA-PK
      by PP1 causes phosphorylation of USF that in turn recruits P/CAF to be acetylated
      for transcriptional activation. SREBP-1c can be induced by mTORC1, bifurcating
      lipogenesis from AKT-activated gluconeogenesis. LXRalpha may serve as a glucose
      sensor and, along with ChREBP, may activate lipogenic genes in the fed state.
      Dysregulation of FA and TAG metabolism often contributes to metabolic diseases
      such as obesity, diabetes, and cardiovascular diseases. Transcription factors and
      signaling molecules involved in transcriptional activation of FA and TAG
      synthesis represent attractive targets for the prevention and treatment of
      metabolic diseases.

PMID- 20817609
TI  - Effects of vitrification solutions and equilibration times on the morphology of
      cynomolgus ovarian tissues.
AB  - This study assessed the effects of vitrification solutions and equilibration
      times on morphology of cynomolgus ovarian tissues. Ovarian cortical sections (0.1
      0.2 cm thickness) of seven cynomolgus monkeys were randomly allocated to either a
      control group or one of six vitrification groups. Ovarian tissue sections were
      vitrified ultra-rapidly by placing them directly into liquid nitrogen using two
      different vitrification solutions (VSEGP: 5.64 mol/l ethylene glycol+5% (w/v)
      polyvinylpyrrolidone+0.5 mol/l sucrose; and VSED: 3.22 mol/l ethylene glycol+2.56
      mol/l dimethylsulphoxide+0.5 mol/l sucrose) after three different exposure times
      (5-20 min). After warming, follicle morphology was analysed using light and
      transmission electron microscopy. The proportion of morphologically normal
      follicles vitrified using VSED after a 5-min exposure was lower (P<0.05) than
      those vitrified by other conditions. The proportion of normally structured
      mitochondria in oocytes of preantral follicles vitrified after a 5-min exposure
      to VSED (56%) was lower (P<0.01) than those vitrified by other conditions (78
      88%). Following tissue vitrification with VSED, the surface ratio of lysosome was
      increased compared with non-vitrified oocytes (1.64% versus 1.11%; P<0.05). These
      results indicate that VSEGP can support the morphology of vitrified preantral
      follicles and oocytes.

PMID- 20817610
TI  - Leukocytapheresis in the treatment of inflammatory bowel disease: Current
      position and perspectives.
AB  - Therapeutic apheresis, a novel approach for immunodisorders, has been used in the
      last decade for the treatment of ulcerative colitis with promising result, and
      represents an alternative to conventional pharmacological therapy. Selective
      apheresis is aimed at reducing the number of circulating lymphocytes, interfering
      with recruitment and activation of mucosal granulocytes and macrophages, reducing
      cytokine and chemokine production which are thought to contribute to induction
      and perpetuation of inflammation. The article briefly reports indications,
      treatment schedule and clinical results of leukocytapheresis in ulcerative
      colitis. Available data for the two selective adsorption devices so far approved
      for clinical use (granulocyte-monocyte apheresis- Adacolumn- and
      leukocytapheresis-Cellsorba) are partially conflicting, and the number of
      controlled studies too small to draw definitive conclusions. Nonetheless
      apheresis definitely appears to be an effective non-conventional tool for the
      treatment of steroid refractory and steroid dependent UC patients with moderately
      active disease. The excellent safety profile of the procedure makes this approach
      attractive, both in adult and in pediatric patients, more so in those refractory
      to conventional drug therapy, who are presently treated with immunosuppressive
      and biological therapies.

PMID- 20817611
TI  - European Heart for Children.

PMID- 20817612
TI  - Catatonia following surgery for temporal lobe epilepsy successfully treated with
      electroconvulsive therapy.
AB  - Catatonia is a psychomotor and behavioral syndrome associated with mood
      disorders, psychotic disorders, neurological disease, and general medical
      conditions. Catatonia has also been described as a manifestation of partial onset
      seizures. We describe a case of catatonia following successful epilepsy surgery.
      A 38-year-old patient with congenital hydrocephalus and left hippocampal
      sclerosis underwent selective left amygdalohippocampectomy for medically
      refractory seizures. Three days after surgery, she became progressively less
      interactive. Verbal output was dramatically reduced. She exhibited waxy
      flexibility, stupor, mutism, posturing, rigidity, negativism, and grimacing.
      Video/EEG monitoring showed no evidence of ongoing seizure activity. She was
      treated with high-dose benzodiazepines for presumed catatonia, but the behavioral
      pattern did not resolve. Subsequently the patient underwent a full course of
      electroconvulsive therapy. Catatonia resolved over the ensuing 3 weeks. Following
      discharge from the hospital, the patient's global functioning returned to the
      premorbid level, and she has been seizure free for more than 4 years.

PMID- 20817613
TI  - Postictal affective episodes.
AB  - Despite their recognition two centuries ago, postictal depression symptoms (PDSs)
      and episodes (PDEs) continue to be ignored by most clinicians in their evaluation
      of patients with epilepsy. And yet, PDSs are relatively frequent in patients with
      pharmacoresistant epilepsy, having been identified in almost 50% of patients with
      a median duration of 24 hours. PDSs may be the expression of symptoms restricted
      to the postictal period (defined as the first 5 days following a seizure) and/or
      may be the expression of postictal exacerbation in severity of interictal
      symptoms of depression. In fact, a past history of depressive and anxiety
      disorders has been associated with the occurrence of PDSs and PSEs. PDSs and PSEs
      often occur together with postictal symptoms of anxiety, and the occurrence of
      PDSs has been associated with more severe postictal cognitive deficits. The
      occurrence of PDSs and PDEs has not been associated with any epilepsy-related
      variable (location of seizure focus, MRI findings, type of antiepileptic drug).
      Prevention of PDSs and PDEs can be achieved only with seizure freedom, and
      preliminary uncontrolled data suggest that being on antidepressant medication
      does not protect patients from experiencing these types of symptoms.

PMID- 20817614
TI  - Neuroprotective effects of leptin following kainic acid-induced status
      epilepticus.
AB  - We investigated the potential neuroprotective effects of leptin (LEP) against
      cellular damage, long-term recurrent spontaneous seizures, and behavioral changes
      associated with kainate (KA)-induced status epilepticus (SE). Adult Sprague
      Dawley rats were sacrificed 24 hours after KA injections, and hippocampi were
      subjected to histological analysis. In the acute condition, one group received 12
      mg/kg KA intraperitoneally (KAac group), and another group received 12 mg/kg KA
      intraperitoneally, followed by two intraperitoneal LEP injections of 4 mg/kg
      each, 1 and 13 hours after KA (KALEPac group). For long-term outcomes, one group
      received KA (KA group), and the other group received three intraperitoneal LEP
      injections (4 mg/kg at 1 hour, and 2mg/kg at 13 and 24 hours) after KA (KALEP
      group). Controls were sham manipulated. Behavioral tests started 6 weeks after
      SE. All rats that received KA underwent behavioral seizures of comparable
      severity. Compared with the KAac group, the KALEPac group had significantly
      larger pyramidal cell surface areas and fewer black-stained degenerating neurons
      with silver stain. The KALEP and KA groups were comparable with respect to
      recurrent spontaneous seizures, aggression, hyperactivity, and impaired memory.
      We show that leptin reduces cellular injury associated with KA-induced SE, but
      does not prevent long-term recurrent spontaneous seizures and behavioral
      deficits.

PMID- 20817615
TI  - Peak and end effects in patients' daily recall of pain and fatigue: a within
      subjects analysis.
AB  - Clinical research often relies on retrospective recall of symptom levels, but the
      information contained in these ratings is not well understood. The "peak-and-end
      rule" suggests that the most intense (peak) and final (end) moments of an
      experience disproportionately influence retrospective judgments, which may bias
      self-reports of somatic symptoms. This study examined the extent to which peak
      and end symptom levels systematically affect patients' day-to-day recall of pain
      and fatigue. Rheumatology patients (N = 97) completed 5 to 6 momentary ratings of
      pain and fatigue per day as well as a daily recall rating of these symptoms for
      28 consecutive days. For pain, peak and end momentary ratings predicted daily
      recall of average pain beyond the actual average of momentary ratings. This
      effect was small, yet was confirmed in both between-person and within-person
      (repeated measures) analyses. For fatigue, neither peak nor end momentary
      symptoms significantly contributed to daily recall. Of note, the evidence for
      peak- and end-effects in recall of pain and fatigue varied significantly between
      individual patients. These findings suggest that peak- and end-effects create a
      small bias in recall reports of pain, but not fatigue. However, there are
      considerable individual differences in susceptibility to peak and end heuristics.
      PERSPECTIVE: The peak-end cognitive heuristic could bias end-of-day recall of
      pain and fatigue. An effect was shown for pain, but not for fatigue. The effects
      were small and were unlikely to substantially bias end-of-day assessments.
      Individuals were shown to differ in the degree that the heuristic was associated
      with recall.

PMID- 20817617
TI  - Dosimetric performance of Strut-Adjusted Volume Implant: a new single-entry
      multicatheter breast brachytherapy applicator.
AB  - PURPOSE: To evaluate the dosimetric performance and clinical utility of the Strut
      Adjusted Volume Implant (SAVI) (Cianna Medical, Aliso Viejo, CA) applicator when
      used as the sole method of radiation therapy for patients with early breast
      carcinoma. METHODS AND MATERIALS: The dosimetric performance of a Phase II
      clinical trial has been reported using the SAVI applicator for patients with
      early breast carcinoma. Cavity volume, planning target volume, dose homogeneity,
      and dose for organs at risk had been calculated. As a result, the D(90) and
      D(100) averages had been presented especially on the distances to the skin and
      the chest wall because these are critical parameters using the MammoSite (Cytyc
      Corp., Marlborough, MA) technique. RESULTS: D(90) and D(100) averages were 95.8%
      and 91.2%, respectively. The average dose homogeneity index was 55.9%. Average
      minimum distances to the skin and chest wall were 15.1 and 23.4mm, respectively.
      The average D(max) values to the skin and ribs were 249 and 199 cGy/fraction,
      respectively. The mean V(20) for the lungs was 17.9 cc. The average V(150) and
      V(200) were 30.80 and 14.91 cc, respectively. CONCLUSIONS: With this study, we
      have been able to optimize dose distribution to obtain clinically acceptable dose
      plans, while minimizing doses to healthy tissues. The dose sculpting versatility
      of SAVI in the clinical setting makes the SAVI applicator a useful addition to
      the tools available for accelerated partial breast irradiation.

PMID- 20817616
TI  - Atypical cadherins Dachsous and Fat control dynamics of noncentrosomal
      microtubules in planar cell polarity.
AB  - How global organ asymmetry and individual cell polarity are connected to each
      other is a central question in studying planar cell polarity (PCP). In the
      Drosophila wing, which develops PCP along its proximal-distal (P-D) axis, we
      previously proposed that the core PCP mediator Frizzled redistributes distally in
      a microtubule (MT)-dependent manner. Here, we performed organ-wide analysis of MT
      dynamics by introducing quantitative in vivo imaging. We observed MTs aligning
      along the P-D axis at the onset of redistribution and a small but significant
      excess of + ends-distal MTs in the proximal region of the wing. This
      characteristic alignment and asymmetry of MT growth was controlled by atypical
      cadherins Dachsous (Ds) and Fat (Ft). Furthermore, the action of Ft was mediated
      in part by PAR-1. All these data support the idea that the active reorientation
      of MT growth adjusts cell polarity along the organ axis.

PMID- 20817618
TI  - A dosimetric comparison of the Contura multilumen balloon breast brachytherapy
      catheter vs. the single-lumen MammoSite balloon device in patients treated with
      accelerated partial breast irradiation at a single institution.
AB  - PURPOSE: A comparison of dosimetric findings in 33 patients treated with the
      Contura multilumen balloon (SenoRx Inc., Irvine, CA) (C-MLB) breast brachytherapy
      catheter vs. 33 patients treated with the MammoSite (Hologic Inc., Bedford, MA)
      (MS) at a single institution to deliver accelerated partial breast irradiation
      (APBI) was performed. METHODS AND MATERIALS: CT-based 3-dimensional planning with
      dose optimization was completed. APBI treatment of 34Gy in 3.4Gy fractions was
      delivered. Endpoints analyzed included: (1) The percentage of the prescribed dose
      (PD) covering the planning target volume (PTV), (2) the maximum skin dose as a
      percentage of the PD, (3) the maximum rib dose as a percentage of the PD, and (4)
      the V150 and V200. RESULTS: The C-MLB was placed more frequently in patients with
      closer skin spacing (<7mm) and rib spacing (<7mm) than in MS patients (45.5% vs.
      12.1%, p=0.0057 and 57.6 vs. 33.3, p=0.0131, respectively). Despite closer skin
      spacing, the overall median skin dose was significantly lower in C-MLB patients
      (112% of the PD vs. 134%, p=0.0282). No statistically significant differences in
      the V150 or V200 were observed. In patients with very limited rib spacing (<4mm),
      the C-MLB delivered significantly lower rib doses than the MS (144% of the PD vs.
      191%, p=0.0107). In all clinical scenarios, coverage of the PTV with the C-MLB
      was either equal to or significantly better than with the MS (p=0.0024).
      CONCLUSION: The C-MLB catheter produced clinically significant improvements in
      dosimetric endpoints (e.g., reduced skin and rib doses and improved PTV coverage)
      in most clinical scenarios.

PMID- 20817619
TI  - Blockade of 5-HT3 receptors at septal area increase blood pressure in
      unanaesthetized rats.
AB  - In the present study the role of 5-HT(3) receptors located at the medial
      septum/vertical limb of the diagonal band complex (MS/vDB) in the control of
      blood pressure in unanaesthetized rats was investigated. Microinjections of
      ondansetron, a selective 5-HT(3) receptor antagonist, into this area caused a
      dose-dependent increase in blood pressure. This rise was attenuated by the
      blockade of alpha-adrenoceptors with i.v. prazosin and blunted by the prior
      microinjection of losartan, an AT1 antagonist, into this brain area.
      Microinjections of the 5-HT(3) agonist m-CPBG into this area failed to have any
      effect on blood pressure in non-stressed rats but significantly reduced the
      stress-induced hypertensive response. The reflex bradycardia evoked by i.v.
      phenylephrine was significantly increased after microinjections of ondansetron
      into this brain area but not the tachycardia evoked by i.v. sodium nitroprusside,
      suggesting that the pressor part of baroreflex has been enhanced. The data
      suggest that 5-HT(3) receptors at this brain level exert a tonic
      sympathoinhibitory action that is mediated via the local release of angiotensin
      in the MS/vDB. This tonic 5-HT(3) receptor drive also exerts an inhibitory action
      on the pressor component of the baroreflex. Also, the present data show that 5
      HT(3) receptors located in the MS/vDB participate in the regulation of stress
      induced hypertensive response.

PMID- 20817620
TI  - Autonomic control of the swimbladder.
AB  - The swimbladder of teleost fishes is the primary organ for controlling whole-body
      density, and thus buoyancy. The volume of gas in the swimbladder is adjusted to
      bring the organism to near neutral buoyancy at a particular depth. Swimbladder
      morphology varies widely among teleosts, but all species are capable of inflating
      and deflating this organ under reflex control by the autonomic nervous system, to
      achieve neutral buoyancy. Here we review the control of effectors within the
      swimbladder, including acid-secreting cells, vasculature and musculature, that
      are involved in determining gas volume. This control system is complex. It
      incorporates the "classical" efferent elements of the autonomic nervous system,
      the spinal autonomic and cranial autonomic limbs and their neurotransmitters
      (typically noradrenaline (NA)/adrenaline (ADR), and acetylcholine, respectively),
      but also non-adrenergic, non-cholinergic neurotransmitters such as peptides,
      purines and nitric oxide. The detailed patterns of autonomic innervation of
      swimbladder effectors are not well understood, nor are the relationships of
      terminals releasing non-adrenergic, non-cholinergic neurotransmitters onto these
      effectors. Furthermore, in most cases the complement of postjunctional receptor
      subtypes activated by adrenergic, cholinergic and other neurotransmitters, and
      the biological effects of these neurochemicals, have not been completely
      established. In order to clarify some of these issues and to provide insight into
      basic principles underlying autonomic control of swimbladder function, we propose
      the zebrafish as a potentially useful model teleost.

PMID- 20817621
TI  - A vital part of a chemo and biosensor is its recognition element responsible for
      selective sensing of a target analyte.

PMID- 20817622
TI  - RecA protein assures fidelity of DNA repair and genome stability in Deinococcus
      radiodurans.
AB  - Deinococcus radiodurans is one of the most radiation-resistant organisms known.
      It can repair hundreds of radiation-induced double-strand DNA breaks without loss
      of viability. Genome reassembly in heavily irradiated D. radiodurans is
      considered to be an error-free process since no genome rearrangements were
      detected after post-irradiation repair. Here, we describe for the first time
      conditions that frequently cause erroneous chromosomal assemblies. Gross
      chromosomal rearrangements have been detected in recA mutant cells that survived
      exposure to 5kGy gamma-radiation. The recA mutants are prone also to spontaneous
      DNA rearrangements during normal exponential growth. Some insertion sequences
      have been identified as dispersed genomic homology blocks that can mediate DNA
      rearrangements. Whereas the wild-type D. radiodurans appears to repair accurately
      its genome shattered by 5kGy gamma-radiation, extremely high gamma-doses, e.g.,
      25kGy, produce frequent genome rearrangements among survivors. Our results show
      that the RecA protein is quintessential for the fidelity of repair of both
      spontaneous and gamma-radiation-induced DNA breaks and, consequently, for genome
      stability in D. radiodurans. The mechanisms of decreased genome stability in the
      absence of RecA are discussed.

PMID- 20817623
TI  - UspB, a member of the sigma-S regulon, facilitates RuvC resolvase function.
AB  - A growing body of evidence shows that there is an intimate connection between
      proteins required for genome stability and stationary phase survival. In this
      work we show that the integral membrane protein UspB, a member of the RpoS
      regulon, is required for proper DNA repair as mutants lacking uspB are
      hypersensitive to several DNA damaging agents including ultraviolet light,
      mitomycin C, bleomycin and ciprofloxacin. Genetic and physical studies
      demonstrate that UspB acts in the RuvABC recombination repair pathway and
      removing uspB creates a phenocopy of the Holliday junction resolvase mutant,
      ruvC. Further, we show that the uspB mutant phenotype can be suppressed by
      ectopic overproduction of RuvC and that both ruvC and uspB mutants can be
      suppressed by inactivating recD. The fact that RuvABC-dependent repair requires
      UspB for proper activity suggests that the sigma-S regulon works together with
      DNA repair pathways under stress conditions to defend the cell against genotoxic
      stress.

PMID- 20817624
TI  - Comparison of 7-day and repeated 24-hour recall of symptoms of cystic fibrosis.
AB  - BACKGROUND: Patient reporting of symptoms in a questionnaire with a 7-day recall
      period is expected to differ from reporting in daily symptom diaries. METHODS: 38
      patients with cystic fibrosis (CF) completed 77 week-long symptom diaries. Each
      diary day comprised 13 symptom items with 5-point response scales. Days 1-6 of
      the diary had a 24-hour recall period. Day 7 had a 7-day recall period.
      Concordance of 7-day recall with summary descriptors of daily reports (e.g. mean,
      maximum) was examined and ability of 7-day recall and mean of daily reports to
      discriminate between well and ill periods of health compared. RESULTS: The
      average difference in scores was less than 0.25 response scale points. 7-day
      recall was most concordant with the mean of daily reports. Discriminant ability
      was comparable. CONCLUSIONS: In this study sample, a questionnaire with 7-day
      recall provided information similar to a daily diary about the week-long
      experience of CF symptoms.

PMID- 20817626
TI  - [New cannabinoids use (Spice) and their detection in emergency departments].

PMID- 20817625
TI  - Normal liver stiffness and its determinants in healthy blood donors.
AB  - BACKGROUND: Several studies in healthy populations have investigated normal liver
      stiffness on transient elastography, but none has excluded subjects with fatty
      liver. AIMS: To define normal liver stiffness and its determinants in 923 healthy
      voluntary blood donors with and without fatty liver. METHODS: Seven hundred and
      forty six subjects were analyzed with transient elastography according to the
      absence (602) or presence of fatty liver (144) at ultrasonography. The cut-off
      for significant fibrosis was a liver stiffness of 7.9kPa. RESULTS: Normal
      subjects had significantly lower liver stiffness (median 4.4kPa) than fatty liver
      subjects (median 5.3, p<0.001). In normal livers male gender was significantly
      associated with increased liver stiffness at multiple linear regression analysis.
      Nine (1.4%) blood donors with normal liver and 9 with fatty liver (6.2%) had
      >7.9kPa. Subjects with verified liver stiffness >7.9kPa, were further
      investigated with liver biopsy or non-invasive fibrosis markers: only 1 patient
      with fatty liver had >F1 fibrosis. CONCLUSIONS: Liver stiffness in normal liver
      is lower than in fatty liver, and gender is the only influencing variable.
      Transient elastography has a very low false positive rate for significant
      fibrosis and may have a role in screening populations at risk for liver disease.

PMID- 20817627
TI  - [Assessment of the secular trend in puberty in boys and girls].
AB  - OBJECTIVE: Changes in the onset of puberty have been reported in the last few
      years. The aim of this study is to determine pubertal trends in boys and girls.
      METHOD: Longitudinal study was conducted on 310 caucasian children. We analysed
      birth weight (BW), weight (kg), height (cm) and body mass index (BMI) (%), bone
      age, duration of puberty growth and pubertal height spurt. RESULTS: For boys the
      mean age at stage 2 was 12.4 (1.5) years with a bone age of 11.9 (1.3) years, and
      stage 5: 15.6 (1.5) with a bone age of 14.5. Mean age (years) (SD) for girls
      stage 2 was 10.1 (1.4), with a bone age of 10.3 (1.1). Age at menarche was 12.0
      (1.3), with a bone age of 13.2 (0.9). Duration of puberty growth for boys was 3
      years (1.2), and for girls 2.5 years (1.1). Pubertal height spurt in boys was
      19.5cm (7.6) and for girls was 15.7cm (5.0). Girls with puberty onset<9 years of
      age show a greater pubertal height gain (19.7cm (4.3)) than girls >9 years of age
      [14.4 (4.5) (P<0.0001)] and a longer period of pubertal growth 3.1 years (0.8)
      versus 2.3 (0.9) (P<0.0001). Boys with puberty onset <11 years of age had a
      greater pubertal height gain [27.3cm (7.9)] than boys > 11 years of age [17.4
      (5.9) (P<0.0001)] and a longer period of puberty growth of 3.9 years (1.2) versus
      2.7 (1.1) (P<0.001). CONCLUSIONS: Boys presented secondary sex characteristics at
      the same age as other studies, but the girls reached puberty and menarche at a
      younger age than previous studies in the Mediterranean area. Bone age correlates
      with chronological age for both sexes at the beginning of puberty but not at the
      end. Early onset of puberty was associated with a greater pubertal height gain
      and a longer period of pubertal growth. There was no correlation between BW or
      BMI with onset of puberty.

PMID- 20817628
TI  - Local cluster of germ cell cancer in a cohort of male automotive workers in
      Germany not explained by previous or concurrent activities and exposures in
      farming and forestry.
AB  - OBJECTIVE: To examine whether exposures or activities in farming, forestry and
      related occupations explain the excess incidence of germ cell cancer (GCC)
      observed among male employees in one of the six car-manufacturing plants that is
      located in a geographic area where farming is frequent. METHODS: A cohort based
      case-control study was conducted among workers in six car-manufacturing plants
      located in areas with different industrial structure. The study involved 188
      cases of germ cell cancer identified through active retrieval in 38 hospitals and
      1000 controls, drawn from administrative accounting files, individually matched
      by year of birth (+/- 2 years). Information regarding tasks and exposures and
      potential confounding variables were obtained by face-to-face or telephone
      interviews. Odds ratios (OR) and 95% confidence intervals (CI) were estimated
      using a conditional logistic regression model adjusted for cryptorchidism and
      other potential confounders. RESULTS: In this case-control study 5.3% of cases
      and 6.3% of controls ever worked in agriculture or livestock farming. No
      increased risks were observed for working in agriculture (OR=0.8 95% CI: 0.4
      1.6), livestock farming (OR=0.8 95% CI: 0.4-1.6) or for exposure to pesticides
      (OR=0.7 95% CI: 0.3-1.7), for exposure to fertilizers (OR=0.8 95% CI: 0.4-1.8)
      and disinfectants (OR=1.0 95% CI: 0.3-2.8). There were no statistically
      significant increases in risk associated with ever exposure to salt based wood
      protection agents (OR=2.3 95% CI: 0.6-9.1), working with plywood (OR=1.4 95% CI:
      0.6-3.2), coated wood (OR=1.4 95% CI: 0.5-3.9) or working in forestry (OR=1.7 95%
      CI: 0.5-6.4). Lagging of exposures did not alter the results. CONCLUSIONS: The
      observed excess incidence in the cohort of automotive workers can be hardly
      explained by previous or concurrent work in farming or forestry. Because of the
      small numbers of subjects ever employed in farming the statistical power in
      assessing associations between agricultural work and agricultural exposures was
      limited and does not allow final conclusions about the association of farming
      related exposures and GCC risk.

PMID- 20817631
TI  - Developing an exchange mindset.
AB  - Exchange is a fundamental concept that underlies all social marketing efforts. In
      a successful exchange, both parties receive something of value and the benefits
      that they desire in return for a price. The purpose of this article is to
      describe how practitioners can develop an "exchange mindset." A practitioner's
      answer to five basic questions will enable him or her to see the exchange through
      the eyes of the customer and increase the likelihood of creating a successful
      exchange that will benefit both parties involved and result in positive behavior
      change.

PMID- 20817630
TI  - Appraising qualitative research in health education: guidelines for public health
      educators.
AB  - Research studies, including qualitative studies, form the basis for evidence
      based practice among health professionals. However, many practicing health
      educators do not feel fully confident in their ability to critically appraise
      qualitative research studies. This publication presents an overview of
      qualitative research approaches, defines key terminology used in qualitative
      research, and provides guidelines for appraising the strengths and weaknesses of
      published qualitative research. On reading, health educators will be better
      equipped to evaluate the quality of the evidence through critical appraisals of
      qualitative research publications.

PMID- 20817632
TI  - The patient-centered medical home and why it matters to health educators.
AB  - The Patient-Centered Medical Home (PCMH) is an approach to providing
      comprehensive care for children, youth, and adults in the primary care setting.
      PCMH emphasizes planned care, care coordination, family-centered approaches, and
      quality of care while also improving access to care and modernizing the care
      experience. Although health educators as a group have not traditionally focused
      their efforts on the primary care setting, the PCMH model increases the potential
      for their inclusion. Health educators, given their training and expertise, are
      likely to be well positioned to contribute to primary care oriented with a PCMH
      model. Health educator roles within PCMH that are especially relevant include
      participating in a team approach to care, attention to coordination and
      integration of care, and preventive and end-of-life care. Such roles may be
      realized in direct delivery of patient education such as health coaching, serving
      as a facilitator or connector to community resources, or involvement in practice
      or practice organization quality improvement and population-based assessment
      efforts. If implemented properly, the involvement of health educators in this new
      model of care has the potential to enhance how primary care is delivered, improve
      the health of Americans with regard to chronic conditions, and reduce related
      health care costs.

PMID- 20817633
TI  - Framing photovoice using a social-ecological logic model as a guide.
AB  - Photovoice is a community-based participatory action research method designed to
      uncover the root causes of community problems and to collectively address them.
      Individual change and empowerment are desired outcomes of the photovoice process,
      but more importantly, the process seeks to engage groups and whole communities to
      foster positive systems change. This article presents a logic model informed by
      the social-ecological model of health to guide photovoice planners and
      participants in planning activities that produce individual-and community-level
      change. The model presented here should help planners and participants plan,
      implement, and evaluate other photovoice efforts and provide them a visual guide
      to ensure that all parties are on the same conceptual page and increase the
      intentionality of their efforts.

PMID- 20817634
TI  - Structures of the lipopolysaccharides from Rhizobium leguminosarum RBL5523 and
      its UDP-glucose dehydrogenase mutant (exo5).
AB  - Rhizobial lipopolysaccharide (LPS) is required to establish an effective
      symbiosis with its host plant. An exo5 mutant of Rhizobium leguminosarum RBL5523,
      strain RBL5808, is defective in UDP-glucose (Glc) dehydrogenase that converts UDP
      Glc to UDP-glucuronic acid (GlcA). This mutant is unable to synthesize either UDP
      GlcA or UDP-galacturonic acid (GalA) and is unable to synthesize extracellular
      and capsular polysaccharides, lacks GalA in its LPS and is defective in symbiosis
      (Laus MC, Logman TJ, van Brussel AAN, Carlson RW, Azadi P, Gao MY, Kijne JW.
      2004. Involvement of exo5 in production of surface polysaccharides in Rhizobium
      leguminosarum and its role in nodulation of Vicia sativa subsp. nigra. J
      Bacteriol. 186:6617-6625). Here, we determined and compared the structures of the
      RBL5523 parent and RBL5808 mutant LPSs. The parent LPS core oligosaccharide (OS),
      as with other R. leguminosarum and Rhizobium etli strains, is a
      Gal(1)Man(1)GalA(3)Kdo(3) octasaccharide in, which each of the GalA residues is
      terminally linked. The core OS from the mutant lacks all three GalA residues.
      Also, the parent lipid A consists of a fatty acylated GlcNGlcNonate or GlcNGlcN
      disaccharide that has a GalA residue at the 4'-position, typical of other R.
      leguminosarum and R. etli lipids A. The mutant lipid A lacks the 4'-GalA residue,
      and the proximal glycosyl residue was only present as GlcNonate. In spite of
      these alterations to the lipid A and core OSs, the mutant was still able to
      synthesize an LPS containing a normal O-chain polysaccharide (OPS), but at
      reduced levels. The structure of the OPS of the mutant LPS was identical to that
      of the parent and consists of an O-acetylated ->4)-alpha-d-Glcp-(1->3)-alpha-d
      QuipNAc-(1-> repeating unit.

PMID- 20817635
TI  - Dissecting the role of the mitochondrial chaperone mortalin in Parkinson's
      disease: functional impact of disease-related variants on mitochondrial
      homeostasis.
AB  - The mitochondrial chaperone mortalin has been linked to neurodegeneration in
      Parkinson's disease (PD) based on reduced protein levels in affected brain
      regions of PD patients and its interaction with the PD-associated protein DJ-1.
      Recently, two amino acid exchanges in the ATPase domain (R126W) and the substrate
      binding domain (P509S) of mortalin were identified in Spanish PD patients. Here,
      we identified a separate and novel variant (A476T) in the substrate-binding
      domain of mortalin in German PD patients. To define a potential role as a
      susceptibility factor in PD, we characterized the functions of all three variants
      in different cellular models. In vitro import assays revealed normal targeting of
      all mortalin variants. In neuronal and non-neuronal human cell lines, the disease
      associated variants caused a mitochondrial phenotype of increased reactive oxygen
      species and reduced mitochondrial membrane potential, which were exacerbated upon
      proteolytic stress. These functional impairments correspond with characteristic
      alterations of the mitochondrial network in cells overexpressing mutant mortalin
      compared with wild-type (wt), which were confirmed in fibroblasts from a carrier
      of the A476T variant. In line with a loss of function hypothesis, knockdown of
      mortalin in human cells caused impaired mitochondrial function that was rescued
      by wt mortalin, but not by the variants. Our genetic and functional studies of
      novel disease-associated variants in the mortalin gene define a loss of mortalin
      function, which causes impaired mitochondrial function and dynamics. Our results
      support the role of this mitochondrial chaperone in neurodegeneration and
      underscore the concept of impaired mitochondrial protein quality control in PD.

PMID- 20817636
TI  - Prevention of autosomal dominant retinitis pigmentosa by systemic drug therapy
      targeting heat shock protein 90 (Hsp90).
AB  - Retinitis pigmentosa (RP) is the most prevalent cause of registered visual
      handicap among working aged populations of developed countries. Up to 40% of
      autosomal dominant cases of disease are caused by mutations within the rhodopsin,
      RDS-peripherin and inosine 5'-monophosphate dehydrogenase type 1 (IMPDH1) genes,
      at least 30 mutations within which give rise to proteins that cause disease
      pathology by misfolding and aggregation. Given the genetic complexity of this
      disease, therapies that simultaneously target multiple mutations are of
      substantial logistic and economic significance. We show here, in a murine model
      of autosomal dominant RP (RP10) involving expression of an Arg224Pro mutation
      within the IMPDH1 gene, that treatment with the low-molecular-weight drug, 17
      allylamino-17-demethoxygeldanamycin (17-AAG), an ansamycin antibiotic that binds
      to heat shock protein Hsp90, activating a heat shock response in mammalian cells,
      protects photoreceptors against degeneration induced by aggregating mutant IMPDH1
      protein, systemic delivery of this low-molecular-weight drug to the retina being
      facilitated by RNA interference-mediated modulation of the inner-blood retina
      barrier. 17-AAG has an orphan drug status and is in current clinical use for the
      treatment of non-ocular diseases. These data show that a single low-molecular
      weight drug has the potential to suppress a wide range of mutant proteins causing
      RP.

PMID- 20817637
TI  - Notch1 mediates visfatin-induced FGF-2 up-regulation and endothelial
      angiogenesis.
AB  - AIMS: Our aims were to determine the role of Notch1 in mediating visfatin-induced
      angiogenesis and to explore potential target genes involved. METHODS AND RESULTS:
      Inhibition of Notch signalling attenuated visfatin-induced angiogenesis in vitro,
      ex vivo, and in vivo. Visfatin increased gamma-secretase activity, Notch1
      cleavage and activation, and Hes1 gene induction. Visfatin also stimulated
      fibroblast growth factor-2 (FGF-2) gene expression in a Notch1-dependent manner.
      Enforced expression of active Notch1 intracellular domain increased FGF-2 protein
      levels and stimulated endothelial tube formation, whereas blocking Notch1
      signalling or knockdown of Notch1 by small interfering RNA suppressed visfatin
      induced FGF-2 up-regulation and angiogenesis. Reporter analysis of FGF-2 promoter
      revealed the presence of CSL (CBF-1, suppressor of hairless, LAG-1)-binding site,
      and chromatin immunoprecipitation analysis demonstrated the binding of Notch1-CSL
      complex to this site in response to visfatin. CONCLUSION: Our data provide the
      first example of Notch1-dependent endothelial FGF-2 induction by visfatin and of
      Notch1 activation in visfatin-stimulated endothelial angiogenesis, suggesting
      that the signalling axis of visfatin/Notch1/angiogenic factors like FGF-2 might
      be a valuable target for pathological angiogenesis.

PMID- 20817638
TI  - The effect of music on robot-assisted laparoscopic surgical performance.
AB  - Music is often played in the operating room to increase the surgeon's
      concentration and to mask noise. It could have a beneficial effect on surgical
      performance. Ten participants with limited experience with the da Vinci robotic
      surgical system were recruited to perform two surgical tasks: suture tying and
      mesh alignment when classical, jazz, hip-hop, and Jamaican music were presented.
      Kinematics of the instrument tips of the surgical robot and surface
      electromyography of the subjects were recorded. Results revealed that a
      significant music effect was found for both tasks with decreased time to task
      completion (P = .005) and total travel distance (P = .021) as well as reduced
      muscle activations ( P = .016) and increased median muscle frequency (P = .034).
      Subjects improved their performance significantly when they listened to either
      hip-hop or Jamaican music. In conclusion, music with high rhythmicity has a
      beneficial effect on robotic surgical performance. Musical environment may
      benefit surgical training and make acquisition of surgical skills more efficient.

PMID- 20817639
TI  - Single access laparoscopic ileocecal resection in complicated Crohn's disease.

PMID- 20817640
TI  - Transethmoidal drainage of frontal brain abscesses.
AB  - BACKGROUND: The frontal lobe is the second most common location for brain abscess
      after the temporal lobe. Since the advent of computed tomography and magnetic
      resonance imaging scanning, diagnosis has become easier, but the prognosis of
      brain abscess is still poor. Treatment is based on antimicrobial therapy and
      neurosurgical evacuation, but controversy still remains as to the merits place of
      each. METHODS: This study describes 2 cases of patients with frontal abscesses
      treated by endonasal transethmoidal sinus surgery (ESS) and reviews the
      literature on this topic. RESULTS: Follow-up revealed no cerebrospinal fluid leak
      in both patients, complete abscess drainage in one patient, and incomplete
      drainage in the other. CONCLUSIONS: ESS drainage of frontal abscesses is feasible
      in intracerebral and epidural abscesses if they have a thick shell and are in
      contact with the skull base. The procedure is minimally invasive and relatively
      simple. It allows for rapid microbial identification and an effective drainage.

PMID- 20817641
TI  - Evaluation of acute fixation strength for mechanical tacking devices and fibrin
      sealant versus polypropylene suture for laparoscopic ventral hernia repair.
AB  - BACKGROUND: The purpose of this comparative study is to evaluate the acute
      fixation strength of mechanical tacking devices and fibrin sealant against
      polypropylene suture for laparoscopic ventral hernia repair. METHODS: Three
      metallic mechanical tacking devices (ProTack, Salute, EndoANCHOR), 4 absorbable
      tacking devices (AbsorbaTack, PermaSorb, I-Clip, and SorbaFix), and 2 types of
      fibrin sealant (Tisseel, Artiss) were compared with 0-polypropylene suture. Three
      constructs from each device or an amount of sealant sufficient to cover a 3 * 3
      cm(2) area were used to affix a 4 * 3 cm piece of absorbable barrier-coated mesh
      (Proceed, Ethicon, Inc) to the peritoneal surface of porcine abdominal wall. Ten
      samples were completed for each fixation modality. Acute fixation strength was
      measured via a lap shear test on an Instron tensiometer. RESULTS: Acute fixation
      strength was significantly greater for suture (59.7 7.2 N) compared with all
      laparoscopic tacking devices and to fibrin sealant (P < .001 for all
      comparisons). Protack (29.5 +/- 2.8 N) was stronger than Absorbatack (13.2 +/-
      3.7 N; P = .029). Protack, Permasorb, SorbaFix, and I-clip were stronger than
      fibrin sealant (P < .05 for all comparisons). CONCLUSIONS: The acute fixation
      strengths of metallic or absorbable tacks as well as fibrin sealant are all
      significantly less than that achieved with polypropylene suture. These factors
      should be considered in selecting the type of mechanical fixation for patients
      undergoing laparoscopic ventral hernia repair.

PMID- 20817642
TI  - Role of GacA in virulence of Vibrio vulnificus.
AB  - The GacS/GacA two-component signal transduction system regulates virulence,
      biofilm formation and symbiosis in Vibrio species. The present study investigated
      this regulatory pathway in Vibrio vulnificus, a human pathogen that causes life
      threatening disease associated with the consumption of raw oysters and wound
      infections. Small non-coding RNAs (csrB1, csrB2, csrB3 and csrC) commonly
      regulated by the GacS/GacA pathway were decreased (P<0.0003) in a V. vulnificus
      CMCP6 DeltagacA : : aph mutant compared with the wild-type parent, and expression
      was restored by complementation of the gacA deletion mutation in trans. Of the 20
      genes examined by RT-PCR, significant reductions in the transcript levels of the
      mutant in comparison with the wild-type strain were observed only for genes
      related to motility (flaA), stationary phase (rpoS) and protease (vvpE) (P=0.04,
      0.01 and 0.002, respectively). Swimming motility, flagellation and opaque colony
      morphology indicative of capsular polysaccharide (CPS) were unchanged in the
      mutant, while cytotoxicity, protease activity, CPS phase variation and the
      ability to acquire iron were decreased compared with the wild-type (P<0.01). The
      role of gacA in virulence of V. vulnificus was also demonstrated by significant
      impairment in the ability of the mutant strain to cause either skin (P<0.0005) or
      systemic infections (P<0.02) in subcutaneously inoculated, non-iron-treated mice.
      However, the virulence of the mutant was equivalent to that of the wild-type in
      iron-treated mice, demonstrating that the GacA pathway in V. vulnificus regulates
      the virulence of this organism in an iron-dependent manner.

PMID- 20817643
TI  - Phenotypic diversification in vivo: Pseudomonas aeruginosa gacS- strains generate
      small colony variants in vivo that are distinct from in vitro variants.
AB  - Pseudomonas aeruginosa has long been known to produce phenotypic variants during
      chronic mucosal surface infections. These variants are thought to be generated to
      ensure bacterial survival against the diverse challenges in the mucosal
      environment. Studies have begun to elucidate the mechanisms by which these
      variants emerge in vitro; however, too little information exists on phenotypic
      variation in vivo to draw any links between variants generated in vitro and in
      vivo. Consequently, in this study, the P. aeruginosa gacS gene, which has
      previously been linked to the generation of small colony variants (SCVs) in
      vitro, was studied in an in vivo mucosal surface infection model. More
      specifically, the rat prostate served as a model mucosal surface to test for the
      appearance of SCVs in vivo following infections with P. aeruginosa gacS(-)
      strains. As in in vitro studies, deletion of the gacS gene led to SCV production
      in vivo. The appearance of these in vivo SCVs was important for the
      sustainability of a chronic infection. In the subset of rats in which P.
      aeruginosa gacS(-) did not convert to SCVs, clearance of the bacteria took place
      and healing of the tissue ensued. When comparing the SCVs that arose at the
      mucosal surface (MS-SCVs) with in vitro SCVs (IV-SCVs) from the same gacS(-)
      parent, some differences between the phenotypic variants were observed. Whereas
      both MS-SCVs and IV-SCVs formed dense biofilms, MS-SCVs exhibited a less diverse
      resistance profile to antimicrobial agents than IV-SCVs. Additionally, MS-SCVs
      were better suited to initiate an infection in the rat model than IV-SCVs.
      Together, these observations suggest that phenotypic variation in vivo can be
      important for maintenance of infection, and that in vivo variants may differ from
      in vitro variants generated from the same genetic parent.

PMID- 20817644
TI  - Intracellular survival of Salmonella enterica serovar Typhi in human macrophages
      is independent of Salmonella pathogenicity island (SPI)-2.
AB  - For successful infection, Salmonella enterica secretes and injects effector
      proteins into host cells by two distinct type three secretion systems (T3SSs)
      located on Salmonella pathogenicity islands (SPIs)-1 and -2. The SPI-2 T3SS is
      involved in intracellular survival of S. enterica serovar Typhimurium and
      systemic disease. As little is known regarding the function of the SPI-2 T3SS
      from S. enterica serovar Typhi, the aetiological agent of typhoid fever, we
      investigated its role for survival in human macrophages. Mutations in the
      translocon (sseB), basal secretion apparatus (ssaR) and regulator (ssrB) did not
      result in any reduction in survival under many of the conditions tested. Similar
      results were obtained with another S. Typhi strain or by using human primary
      cells. Results were corroborated based on complete deletion of the SPI-2 T3SS.
      Surprisingly, the data suggest that the SPI-2 T3SS of S. Typhi is not required
      for survival in human macrophages.

PMID- 20817645
TI  - ccrABEnt serine recombinase genes are widely distributed in the Enterococcus
      faecium and Enterococcus casseliflavus species groups and are expressed in E.
      faecium.
AB  - The presence, distribution and expression of cassette chromosome recombinase
      (ccr) genes, which are homologous to the staphylococcal ccrAB genes and are
      designated ccrAB(Ent) genes, were examined in enterococcal isolates (n=421)
      representing 13 different species. A total of 118 (28 %) isolates were positive
      for ccrAB(Ent) genes by PCR, and a number of these were confirmed by Southern
      hybridization with a ccrA(Ent) probe (n=76) and partial DNA sequencing of
      ccrA(Ent) and ccrB(Ent) genes (n=38). ccrAB(Ent) genes were present in
      Enterococcus faecium (58/216, 27 %), Enterococcus durans (31/38, 82 %),
      Enterococcus hirae (27/52, 50 %), Enterococcus casseliflavus (1/4, 25 %) and
      Enterococcus gallinarum (1/2, 50 %). In the eight other species tested, including
      Enterococcus faecalis (n=94), ccrAB(Ent) genes were not found. Thirty-eight
      sequenced ccrAB(Ent) genes from five different enterococcal species showed 94-100
      % nucleotide sequence identity and linkage PCRs showed heterogeneity in the
      ccrAB(Ent) flanking chromosomal genes. Expression analysis of ccrAB(Ent) genes
      from the E. faecium DO strain showed constitutive expression as a bicistronic
      mRNA. The ccrAB(Ent) mRNA levels were lower during log phase than stationary
      phase in relation to total mRNA. Multilocus sequence typing was performed on 39
      isolates. ccrAB(Ent) genes were detected in both hospital-related (10/29, 34 %)
      and non-hospital (4/10, 40 %) strains of E. faecium. Various sequence types were
      represented by both ccrAB(Ent) positive and negative isolates, suggesting
      acquisition or loss of ccrAB(Ent) in E. faecium. In summary, ccrAB(Ent) genes,
      potentially involved in genome plasticity, are expressed in E. faecium and are
      widely distributed in the E. faecium and E. casseliflavus species groups.

PMID- 20817646
TI  - Cytokeratin 8 interacts with clumping factor B: a new possible virulence factor
      target.
AB  - Staphylococcus aureus is a human pathogen of growing clinical significance, owing
      to its increasing levels of resistance to most antibiotics. Infections range from
      mild wound infections to severe infections such as endocarditis, osteomyelitis
      and septic shock. Adherence of S. aureus to human host cells is an important
      step, leading to colonization and infection. Adherence is mediated by a
      multiplicity of proteins expressed on the bacterial surface, including clumping
      factor B. In this study, we aimed to identify new targets of clumping factor B in
      human keratinocytes by undertaking a genome-wide yeast two-hybrid screen of a
      human keratinocyte cDNA library. We show that clumping factor B is capable of
      binding cytokeratin 8 (CK8), a type II cytokeratin. Using a domain-mapping
      strategy we identified amino acids 437-464 as necessary for this interaction.
      Recombinantly expressed fragments of both proteins were used in pull-down
      experiments and confirmed the yeast two-hybrid studies. Analysis with S. aureus
      strain Newman deficient in clumping factor B showed the clumping factor B
      dependence of the interaction with CK8. We postulate that the clumping factor B
      CK8 interaction is a novel factor in S. aureus infections.

PMID- 20817648
TI  - Anterior transposition of the ulnar nerve with endoscopic assistance.
AB  - We treated 20 patients with cubital tunnel syndrome by anterior transposition of
      the ulnar nerve with endoscopic assistance. Five elbows were classified
      preoperatively as McGowan's stage 1, 11 as stage 2 and four as stage 3. Excellent
      outcomes were obtained in nine and good in eight patients. Three patients had
      fair results. Improvement of symptoms occurred in all patients. There were no
      serious complications. All ulnar nerves remained anteriorly transposed.

PMID- 20817647
TI  - Variation in the Neisseria meningitidis FadL-like protein: an evolutionary model
      for a relatively low-abundance surface antigen.
AB  - The molecular diversity of a novel Neisseria meningitidis antigen, encoded by the
      ORF NMB0088 of MC58 (FadL-like protein), was assessed in a panel of 64 diverse
      meningococcal strains. The panel consisted of strains belonging to different
      serogroups, serotypes, serosubtypes and MLST sequence types, of different
      clinical sources, years and countries of isolation. Based on the sequence
      variability of the protein, the FadL-like protein has been divided into four
      variant groups in this species. Antigen variants were associated with specific
      serogroups and MLST clonal complexes. Maximum-likelihood analyses were used to
      determine the relationships among sequences and to compare the selection
      pressures acting on the encoded protein. Furthermore, a model of population
      genetics and molecular evolution was used to detect natural selection in DNA
      sequences using the non-synonymous : synonymous substitution (d(N) : d(S)) ratio.
      The meningococcal sequences were also compared with those of the related surface
      protein in non-pathogenic commensal Neisseria species to investigate potential
      horizontal gene transfer. The N. meningitidis fadL gene was subject to only weak
      positive selection pressure and was less diverse than meningococcal major outer
      membrane proteins. The majority of the variability in fadL was due to
      recombination among existing alleles from the same or related species that
      resulted in a discrete mosaic structure in the meningococcal population. In
      general, the population structuring observed based on the FadL-like membrane
      protein indicates that it is under intermediate immune selection. However, the
      emergence of a new subvariant within the hyperinvasive lineages demonstrates the
      phenotypic adaptability of N. meningitidis, probably in response to selective
      pressure.

PMID- 20817649
TI  - Tendon adhesion measured by a video-assisted gliding test in a chicken model.
AB  - We developed a video-assisted gliding test to evaluate the gliding force and the
      flexion angle with unrestricted joint motion. Tendon adhesion was induced in a
      chicken model of flexor digitorum profundus (FDP) injury at the annular pulley
      region of the long toe. The chicken feet were harvested immediately after injury,
      and 2 weeks and 6 weeks after injury. During the gliding test, the injured FDP
      was pulled for 15 mm then returned to its initial position. The test was recorded
      using a video camera and registered to the gliding test mechanical data. The
      maximum flexion angle and gliding resistance were calculated. The maximum flexion
      angle was significantly decreased from 78 (SD 10) in controls to 42 (SD 22) in
      tendons with injury, while gliding resistance was significantly increased in week
      2 (0.06, SD 0.05) and week 6 (0.07, SD 0.01) after injury.

PMID- 20817650
TI  - Estimating causal effects using prior information on nontrial treatments.
AB  - BACKGROUND: Departures from randomized treatments complicate the analysis of many
      randomized controlled trials. Intention-to-treat analysis estimates the effect of
      being allocated to treatment. It is now possible to estimate the effect of
      receiving treatment without assuming comparability of groups defined by actual
      treatment. However, the methodology is largely confined to trials where the only
      treatment changes were switches to other trial treatments. PURPOSE: To propose a
      method for comparing the effects of receiving trial treatments in an active
      controlled clinical trial where some participants received nontrial treatments
      and others received no treatment at all, and to illustrate the method in the
      PENTA 5 trial in HIV-infected children. METHODS: We combine the instrumental
      variables approach, which forms unbiased estimating equations based on the
      randomization but does not fully identify the contrasts of trial treatment
      effects, with prior information about the distribution of possible effects of
      nontrial treatments and of one trial treatment; we do not need to use prior
      information about the comparisons of trial treatments. Prior information in PENTA
      5 was elicited from the investigators. RESULTS: In PENTA 5, the prior information
      suggested that all treatments were beneficial, but there was uncertainty about
      the degree of benefit. Allowing for this prior information changed point
      estimates and increased standard errors compared with ignoring nontrial
      treatments. LIMITATIONS: The method depends on the correct specification of the
      causal effect of treatment: in PENTA 5, this assumed a linear effect of dose and
      no interactions between treatments. This specification is hard to check from the
      data but can be explored in sensitivity analyses. Prior information would be
      better derived from the literature whenever possible. CONCLUSIONS: The use of
      partial prior information gives a way to adjust for complex patterns of
      departures from randomized treatments. It should be useful in all trials where
      nontrial treatments are used and in active-controlled trials where trial
      treatments are not universally used.

PMID- 20817651
TI  - The effect of monotherapy and combined therapy with NSC-631570 (ukrain) on growth
      of low- and high-metastasizing B16 melanoma in mice.
AB  - BACKGROUND: NSC-631570 (ukrain) is a semisynthetic derivative of the Chelidonium
      majus alcaloids and the alkylans thiotepa. It exerts a selective cytotoxic effect
      on tumor cells in vitro and in vivo and shows the ability to modulate immunocyte
      functions. Purpose. The aim of our work was to carry out a comparative
      investigation of the effects of NSC-631570 alone or in combination with pathogen
      associated molecules (PAM) on the growth of low- and high-metastasizing melanoma
      B16 in mice. METHODS: NSC-631570 was administered intravenously and PAM
      intramuscularly to tumor-bearing mice seven times every third day, starting from
      the second day after the transplantation of tumor cells. The effect of
      monotherapy and combined therapy on tumor growth was evaluated by the indices of
      tumor growth inhibition in experimental animals. Cell cycle distribution of
      cancer cells was determined by flow cytometry. TAP1 and TAP2 expression was
      evaluated by RT-PCR. The metabolic activity of phagocytes was determined by NBT
      test, phagocytosis was tested by flow cytometry, and arginase activity was
      estimated by colorimetric determination of urea. RESULTS: Combined therapy and
      monotherapy with NSC-631570 resulted in significant inhibition of tumor growth in
      melanoma-bearing mice. Monotherapy with Ukrain was more effective in mice with
      high-metastasizing tumors. The therapeutic efficacy of NSC-631570 used in
      combination with PAM was more expressed in mice with low-metastasizing melanoma.
      CONCLUSION: The effectiveness of monotherapy and combined therapy with NSC-631570
      in the treatment of melanoma B16 depends on the biological properties of the
      tumor and the immune state of the organism.

PMID- 20817652
TI  - Blood pressure control in patients receiving bevacizumab in an outpatient cancer
      center.
AB  - PURPOSE: Hypertension is a common adverse effect of vascular endothelial growth
      factor (VEGF) signaling inhibitors, such as bevacizumab, with an incidence
      upwards of 35%. The management of bevacizumab-induced hypertension is important
      in order to avoid dose interruption/discontinuation and/or end organ damage. The
      efficacy of antihypertensive medications for this cause of hypertension has not
      been demonstrated. This study seeks to determine if antihypertensives are
      effective in treating anti-VEGF-induced hypertension from bevacizumab and
      determine which classes of antihypertensive agents are effective. METHODS: A
      retrospective review of all patients who received bevacizumab between January
      2007 and September 2009 at two medical centers was conducted. Patients were
      included if they experienced new onset or exacerbation of preexisting
      hypertension, during bevacizumab treatment. Efficacy of antihypertensives was
      determined by recording a 28-day change in systolic blood pressure from the
      initiation or dose increase of individual antihypertensive medications. Secondary
      endpoints included an efficacy analysis of antihypertensive classes. RESULTS:
      Five-hundred thirteen patients were identified as receiving bevacizumab during
      the indicated time period. Fifty-seven patients met the full inclusion/exclusion
      criteria for analysis. The average systolic blood pressure declined by 23  mm Hg
      with 4 weeks of treatment (p < 0.0001). Each class had a statistically
      significant decline in systolic blood pressure of 15.5-57 mm Hg with the
      exception of diuretics and a group of miscellaneous antihypertensives.
      CONCLUSIONS: This is the first data that demonstrates individual classes of
      antihypertensives are effective in bevacizumab-induced hypertension. Most
      antihypertensives were effective in reducing blood pressure, with the exception
      of diuretics and miscellaneous antihypertensives, which may be due to a limited
      sample size.

PMID- 20817653
TI  - Adding a physical exercise programme to brief intervention for low back pain
      patients did not increase return to work.
AB  - AIMS: To investigate if a standardised physical exercise programme given in
      addition to a brief intervention at a spine clinic had an effect on return to
      work. METHODS: A total of 246 patients sick-listed 8-12 weeks for non-specific
      low back pain were offered a brief intervention programme at the spine clinic
      with examination, information, reassurance, and encouragement to engage in
      physical activity as normal as possible, before they were randomised into an
      intervention group (n = 124) and a control group (n = 122). Patients in the
      intervention group participated in a physical exercise programme at the spine
      clinic. RESULTS: During the 2-year follow-up, there were no significant
      differences between the groups on sick leave, pain, use of analgesics,
      psychological distress, coping strategies, fear-avoidance beliefs, self-reported
      disability, or walking distances. However, both groups increased return to work,
      reported less pain and better function, and reduced fear-avoidance beliefs for
      physical activity during the follow-up period. Fear-avoidance beliefs for work
      were not changed. CONCLUSIONS: A physical exercise programme for low back pain
      patients given after a brief intervention at a spine clinic did not have any
      additional effect on sick leave or fear-avoidance beliefs. Both groups reported
      less pain, better physical function, and increased return to work during follow
      up. The treatment at the spine clinic did not contain a vocational rehabilitation
      programme directed towards individual work-related problems, which might explain
      no change in fear-avoidance beliefs for work.

PMID- 20817654
TI  - Review Article: Health benefit of increased serum 25(OH)D levels from oral intake
      and ultraviolet-B irradiance in the Nordic countries.
AB  - AIMS: A low serum 25-hydroxyvitamin D [25(OH)D] level is a risk factor for many
      diseases, including musculoskeletal diseases, many types of cancer,
      cardiovascular diseases, diabetes mellitus, infectious diseases, autoimmune
      diseases, and brain diseases. This report estimates the reduction in mortality
      rates for the five Nordic countries for an increase in population mean serum 25
      hydroxyvitamin D level to 105 nmol/L. METHODS: Serum vitamin D dose
      incidence/prognosis relationships can be developed with significant levels of
      reliability for most vitamin D-sensitive diseases on the basis of ecological,
      cross-sectional, and observational studies, randomized controlled trials, and
      meta-analysis of such studies. These dose-response relations are used to estimate
      the population-wide benefit of raising mean serum 25(OH)D concentration to 105
      nmol/L for the five Nordic countries. RESULTS: From this study, the reductions in
      mortality rates possible by raising population mean serum 25(OH)D levels to 105
      nmol/L are: Denmark, 17% (estimated range,11%-24%); Finland, 24% (17%-32%);
      Iceland, 24% (17%-32%); Norway, 18% (11%-26%); and Sweden, 18% (8%-25%).
      CONCLUSIONS: Reaching these levels would require changes in health policies with
      respect to solar ultraviolet-B (UVB) irradiance, vitamin D fortification of food,
      availability of vitamin D and calcium supplements, and attitude toward use of UVB
      lamps. Adverse effects of oral vitamin D intake are limited, and those from UVB
      irradiance are minor compared with the benefits.

PMID- 20817655
TI  - Disaster preparedness of families with young children in Hong Kong.
AB  - AIMS: The aims of this study were to explore the perception of disaster among the
      head of household mainly responsible for family matters of Hong Kong families
      with young children, and the extent of their preparedness for disasters.
      BACKGROUND: Being prepared for disasters can minimize damage to our health,
      lives, and property. Families with young children are particularly vulnerable
      during disasters. METHODS: A questionnaire was distributed to a convenience
      sample of families with young children in March and September in 2008. RESULTS: A
      total of 198 out of 220 questionnaires distributed to heads of households were
      collected and analyzed for this study. Most of the householders (94.4%)
      considered the SARS outbreak in Hong Kong in 2003 to have been a disaster. They
      considered that the disastrous events most likely to occur in Hong Kong were
      infectious disease outbreaks (96.5%) and major transport accidents (94.4%). In
      preparing for unexpected events, these families reported having stocked up on
      ''young children's necessities'' (82.8%, 73.7%) and ''medications'' (82.8%,
      60.1%) sufficient for three and seven days respectively. These families also kept
      a flashlight with adequate batteries (74.7%), extra blankets (69.2%), and a first
      aid kit (60.6%) at home for safety. They reported ''panic buying'' for
      necessities during previous typhoon strikes (68.2%) and infectious disease
      outbreaks (46.0%). Only 9.1% considered themselves adequately prepared for
      disasters (9.1%). CONCLUSIONS: Although the families with young children in this
      study are prepared for disaster to some extent, their preparedness is still
      considered grossly inadequate and in need of public attention.

PMID- 20817656
TI  - Lower immunglobulin A levels but not lower cortisol or &alpha;-amylase activity
      in children with chronic tension-type headache.
AB  - OBJECTIVE: The study was designed to investigate the differences in salivary
      cortisol (hypothalamic-pituitary-adrenocortical [HPA] axis), immunoglobulin A
      (IgA) (immune system) concentrations and alpha-amylase (sympathetic nervous
      system [SNS]) activity between children with chronic tension-type headache (CTTH)
      and healthy children. METHODS: Thirty-six children, 10 boys and 26 girls (age: 9
      +/- 2 years) with CTTH and 36 age- and sex-matched healthy children were
      recruited. Salivary cortisol, alpha-amylase activity, salivary flow rate, IgA
      concentration and IgA rate were collected from non-stimulated saliva. A headache
      diary was used for collecting data on intensity, frequency and duration of
      headache for four weeks. RESULTS: Children with CTTH showed lower IgA
      concentration (p = .008) and IgA rate (p = .039), but not lower cortisol
      concentration (p = .447), salivary flow rate (p = .289) or alpha-amylase activity
      (p = .559), as compared to healthy children. Neither age (p > .582) nor gender (p
      > .227) influenced salivary markers. A significant association between the number
      of years with headache and IgA concentration (r(s) = - 0.385; p = .023) was
      found: the greater the number of years with headache, the lower the IgA
      concentration. CONCLUSIONS: These results suggest that children with CTTH present
      with deficits in the immune system, but not dysfunction in the HPA axis or SNS.
      Future studies are needed to elucidate the direction of these relationships.

PMID- 20817657
TI  - ICHD-II criteria for headache attributed to transient ischemic attack: the need
      for an update.

PMID- 20817658
TI  - The prevalence and characteristics of alcohol-related presentations to emergency
      departments in rural Australia.
AB  - BACKGROUND: The burden of harm associated with alcohol misuse is
      disproportionately high in rural areas of Australia, and a considerable
      proportion of this burden is borne by the health system. The health impact of
      alcohol in rural areas has been measured in terms of the contribution of alcohol
      to hospital inpatient admissions and mortality rates, despite many more alcohol
      related cases presenting to emergency departments (EDs). This study aims to
      estimate the proportion of presentations to EDs in rural Australia that are
      alcohol-related and to identify the associated patient and presentation
      characteristics. METHODS: Patients aged >=14 years presenting to four EDs in
      rural NSW were assessed on two measures: (1) Clinician judgement of alcohol
      consumption, and (2) patient self-report of alcohol consumption in the 6 h
      preceding the onset of their condition. RESULTS: Preliminary analyses revealed
      sample selection biases in two of the EDs, and these samples were consequently
      excluded from further analyses. In the two remaining EDs, 46% of presentations
      were assessed, of which 9% were identified as alcohol-related. Presentations for
      mental disorders, those with more urgent triage categories and those occurring on
      weekends or at night were more often alcohol-related. CONCLUSIONS: The prevalence
      of alcohol-related ED presentations observed was at the lower end of the
      documented range, probably due to methodological differences and limitations, as
      well as geographic variation. Despite this, alcohol-related presentations were
      associated with a substantial impact on the ED. Policies and programs to reduce
      the impact of alcohol on rural emergency departments are needed.

PMID- 20817659
TI  - Patients' perspectives on injuries.
AB  - AIM AND METHODS: To assess the way different terms used to describe a fracture
      affect the understanding a patient has of that fracture. The perceived severity
      of the injury and how the patient expects to be treated were also recorded with a
      view to optimising patient understanding. RESULTS: There was a very significant
      difference between what doctors can potentially say and what the patient
      ultimately understood about the consultation. This could have a direct effect on
      the management the patient expects from the initial description and diagnosis.
      CONCLUSIONS: It is important that doctors in the emergency department use
      terminology that is understood by the patient, as well as emphasising the
      potential seriousness of the injury. It is possibly better therefore to use
      informed lay terminology such as 'a break in a bone' rather than more formal
      vocabulary such 'a fracture' when discussing the diagnosis and treatment options.

PMID- 20817660
TI  - Gender inequality in the risk of violence: material deprivation is linked to
      higher risk for adolescent girls.
AB  - OBJECTIVE: To investigate the association between material deprivation and injury
      sustained in violence by adolescents aged 11-17 years. METHODS: Computerised data
      relating to gender, attendance date and resident postcode of all patients aged 11
      17 years who received treatment for violence-related injuries at seven emergency
      departments (ED) in South Wales over 12 months, 1 October 2005 to 30 September
      2006, were studied. The resident populations, by electoral division of three
      unitary authorities in Wales, Cardiff, Swansea and Newport, were obtained from
      the NHS administrative register. The relationships between demographic variables
      and material deprivation as measured by the Townsend deprivation index were
      analysed. RESULTS: Altogether 699 (475 boys; 224 girls) adolescents aged 11-17
      years resident in Cardiff, Swansea and Newport attended ED in South Wales
      following violence. Boys and girls living in the most deprived areas had higher
      assault injury rates compared with those living in the most affluent areas. In
      the context of sustaining violence-related injury, material deprivation affected
      girls aged 11-17&emsp14;years to a much greater extent (Cardiff most deprived vs
      most affluent rate ratio 6.31, Swansea 10.11, Newport 2.90) than boys of the same
      age group (Cardiff most deprived vs most affluent rate ratio 2.02, Swansea 7.74,
      Newport 1.74). CONCLUSIONS: Material deprivation was associated with a higher
      risk of violence-related injury for adolescent girls compared with adolescent
      boys. Risk-taking behaviour for adolescent boys and girls may be different under
      different socioeconomic conditions. Violence prevention efforts should focus more
      on tackling neighbourhood inequalities, particularly those related to material
      deprivation in adolescent girls.

PMID- 20817661
TI  - The use of inhaled methoxyflurine as an analgesic in prehospital care.

PMID- 20817662
TI  - The UK medical response to the Sichuan earthquake.
AB  - BACKGROUND: At 14:48 on 12 May 2008 an earthquake of magnitude 8.0 struck the
      Wenchuan area of Sichuan province, China. A decision to offer/receive UK medical
      assistance was agreed at a Sino/British political level and a medical team was
      despatched to the earthquake area. METHODS: This study describes the team's
      experience during the immediate aftermath of the earthquake and the following 18
      months, during which there have been joint developments in emergency medicine,
      disaster planning/preparedness and the management of spinal cord injury. RESULTS:
      The long-term disability following sudden onset natural disaster and the wider
      impact on healthcare delivery may prove to be a greater burden to the country
      than the immediate medical needs, and, accordingly, emergency international aid
      may need to widen its focus. Although international teams usually arrive too late
      to support resuscitative measures, they can respond to specific requests for
      specialised assistance, for example plastic and reconstructive surgery to assist
      with the ongoing management of complex injury, relieve those who have worked
      continuously through the disaster, and when required maintain routine day-to-day
      services while local staff continue to manage the disaster. The timing of this
      does not necessarily need to be immediate. CONCLUSIONS: To maximise its impact,
      the team planned from the outset to build a relationship with Chinese colleagues
      that would lead to a sharing of knowledge and experience that would benefit major
      incident responses in both countries in the future. This has been established,
      and the linkage of emergency humanitarian assistance to longer term development
      should be considered by others the next time international emergency humanitarian
      assistance is contemplated.

PMID- 20817663
TI  - An evaluation of the UK National Pandemic Flu Service swine flu algorithm in
      hospitalised children, and comparison with the UK National Institute for Health
      and Clinical Excellence fever guideline.
AB  - AIM: To evaluate the efficacy of the UK swine flu algorithm as a screening tool
      in unwell children, and to compare the management advice given with the National
      Institute for Health and Clinical Excellence (NICE) feverish illness guideline
      advice. METHOD: All paediatric medical admissions to the unit, with a fever and
      over the age of 1 year, during 2 weeks in November were analysed, and their
      histories were put through both the swine flu algorithm and the NICE fever
      guidance for the under 5s. RESULTS: Of 72 patients, 71 would have had a diagnosis
      of swine flu had their symptoms been put through the algorithm. Two patients had
      confirmed swine flu on testing, and 32 patients definitely did not have swine
      flu. The positive predictive value of the algorithm is between 2.8% and 56.3% in
      this population. 39% would have been advised to have a face-to-face consultation
      by the NICE guidance, but would not have been advised to have an urgent
      consultation by the swine flu guidance. At least 79% of patients had treatments
      only available in hospitals. CONCLUSIONS: The swine flu algorithm is of little
      use in differentiating unwell children, and advice given does not correlate well
      with that of the NICE guidance. There is a significant risk of harm with false
      positive diagnoses and potential delays in appropriate treatment. The authors
      were unable to obtain the data and rationale behind the algorithm, and believe
      that this should be published. Face-to-face consultations may be the only way to
      ensure patient safety.

PMID- 20817664
TI  - When the bone in your swallow is your own.

PMID- 20817666
TI  - Maternal growth factor regulation of human placental development and fetal
      growth.
AB  - Normal development and function of the placenta is critical to achieving a
      successful pregnancy, as normal fetal growth depends directly on the transfer of
      nutrients from mother to fetus via this organ. Recently, it has become apparent
      from both animal and human studies that growth factors within the maternal
      circulation, for example the IGFs, are important regulators of placental
      development and function. Although these factors act via distinct receptors to
      exert their effects, the downstream molecules activated upon ligand/receptor
      interaction are common to many growth factors. The expression of numerous
      signaling molecules is altered in the placentas from pregnancies affected by the
      fetal growth complications, fetal growth restriction, and macrosomia. Thus,
      targeting these molecules may lead to more effective treatments for complications
      of pregnancy associated with altered placental development. Here, we review the
      maternal growth factors required for placental development and discuss their
      mechanism of action.

PMID- 20817665
TI  - Changes in functioning of mesolimbic incentive processing circuits during the
      premenstrual phase.
AB  - The premenstrual phase of the menstrual cycle is associated with marked changes
      in normal and abnormal motivated behaviors. Animal studies suggest that such
      effects may result from actions of gonadal hormones on the mesolimbic dopamine
      (DA) system. We therefore investigated premenstrual changes in reward-related
      neural activity in terminal regions of the DA system in humans. Twenty-eight
      healthy young women underwent functional magnetic resonance imaging on 2 days
      during the menstrual cycle, once during the late follicular phase and once during
      the premenstrual phase, in counterbalanced order. Using a modified version of the
      monetary incentive delay task, we assessed responsiveness of the ventral striatum
      to reward anticipation. Our results show enhanced ventral striatal responses
      during the premenstrual as compared to the follicular phase. Moreover, this
      effect was most pronounced in women reporting more premenstrual symptoms. These
      findings provide support for the notion that changes in functioning of mesolimbic
      incentive processing circuits may underlie premenstrual changes in motivated
      behaviors. Notably, increases in reward-cue responsiveness have previously been
      associated with DA withdrawal states. Our findings therefore suggest that the
      sharp decline of gonadal hormone levels in the premenstrual phase may trigger a
      similar withdrawal-like state.

PMID- 20817667
TI  - Lethal varicella-zoster virus reactivation without skin lesions following renal
      transplantation.
AB  - Patients after solid organ transplantation are at increased risk of developing
      herpes zoster and are more likely to develop major complications such as
      cutaneous dissemination, post-herpetic neuralgia and visceral organ involvement.
      We report on a 68-year-old woman being varicella-zoster virus (VZV)-seropositive
      prior to transplantation, who developed fatal VZV meningoencephalitis after renal
      transplantation presenting with non-specific neurologic symptoms. The case
      illustrates that VZV reactivation may occur in renal transplant recipients in the
      absence of skin lesions. Approaches towards risk assessment pre-transplantation
      and prophylactic regimens for the prevention of VZV recurrence are needed.

PMID- 20817668
TI  - Risk factors for the development of albuminuria and renal impairment in type 2
      diabetes--the Swedish National Diabetes Register (NDR).
AB  - BACKGROUND: The aim of this study was to identify clinical risk factors
      associated with the development of albuminuria and renal impairment in patients
      with type 2 diabetes (T2D). In addition, we evaluated if different equations to
      estimate renal function had an impact on interpretation of data. This was done in
      a nationwide population-based study using data from the Swedish National Diabetes
      Register. METHODS: Three thousand and six hundred sixty-seven patients with T2D
      aged 30-74 years with no signs of renal dysfunction at baseline (no albuminuria
      and eGFR >60 mL/min/1.73 m(2) according to MDRD) were followed up for 5 years
      (2002-2007). Renal outcomes, development of albuminuria and/or renal impairment
      [eGFR < 60 mL/min/1.73 m(2) by MDRD or eCrCl > 60 mL/min by Cockgroft-Gault (C
      G)] were assessed at follow-up. Univariate regression analyses and stepwise
      regression models were used to identify significant clinical risk factors for
      renal outcomes. RESULTS: Twenty percent of patients developed albuminuria, and
      11% renal impairment; thus, ~6-7% of all patients developed non-albuminuric renal
      impairment. Development of albuminuria or renal impairment was independently
      associated with high age (all P < 0.001), high systolic BP (all P < 0.02) and
      elevated triglycerides (all P < 0.02). Additional independent risk factors for
      albuminuria were high BMI (P < 0.01), high HbA1c (P < 0.001), smoking (P <
      0.001), HDL (P < 0.05) and male sex (P < 0.001), and for renal impairment
      elevated plasma creatinine at baseline and female sex (both P < 0.001). High BMI
      was an independent risk factor for renal impairment when defined by MDRD (P <
      0.01), but low BMI was when defined by C-G (P <  0.001). Adverse effects of BMI
      on HbA1c, blood pressure and lipids accounted for ~50% of the increase risk for
      albuminuria, and for 41% of the increased risk for renal impairment (MDRD).
      CONCLUSIONS: Distinct sets of risk factors were associated with the development
      of albuminuria and renal impairment consistent with the concept that they are not
      entirely linked in patients with type 2 diabetes. Obesity and serum triglycerides
      are semi-novel risk factors for development of renal dysfunction and BMI
      accounted for a substantial proportion of the increased risk. The equations used
      to estimate renal function (MDRD vs. C-G) had an impact on interpretation of
      data, especially with regard to body composition and gender.

PMID- 20817669
TI  - Evolution of renal oxygen content measured by BOLD MRI downstream a chronic renal
      artery stenosis.
AB  - BACKGROUND: A decrease in renal oxygen content can be measured non-invasively by
      the increase of the R2* value derived from blood oxygen level-dependent magnetic
      resonance imaging (BOLD MRI). The aim of this study was to test if renal hypoxia
      occurs in kidneys downstream a chronic and unilateral renal artery stenosis.
      METHODS: Chronic renal ischaemia was induced in rats using a calibrated clip
      inserted on the right renal artery. R2* was determined, using a multiple recalled
      gradient-echo sequence, before and once a week after a clip insertion over 4
      weeks, in a group of clipped (n = 8) and sham-operated (n = 7) rats. RESULTS: At
      baseline, in stenotic kidneys, R2* was higher in the outer stripe of outer
      medulla (105 +/- 4.6) and the outer medulla (99 +/- 2.5) than in the cortex (84
      +/- 2.5; P < 0.002 for comparison with both areas). R2* was unchanged in the
      cortex, the outer stripe of outer medulla and the outer medulla in stenotic
      kidneys, sham-operated kidneys and contralateral kidneys during the 4 weeks. Mean
      blood pressure was higher in rats with clipped kidney than in sham-operated rats
      from Day 11 and remained increased thereafter. The renal volume increased
      progressively in sham-operated kidneys and contralateral kidneys, whereas it
      slightly decreased in stenotic kidneys. CONCLUSIONS: Our study shows that after 4
      weeks, no renal hypoxia can be detected in the kidney downstream to a renal
      artery stenosis, suggesting that atrophy could be induced by other factors.

PMID- 20817670
TI  - Decreased plasma level of vitamin C in chronic kidney disease: comparison between
      diabetic and non-diabetic patients.
AB  - BACKGROUND: A decreased plasma level of vitamin C has been reported to be
      associated with an increased risk of cardiovascular morbidity and mortality.
      Here, we sought to determine the vitamin C status of patients with chronic kidney
      disease and the pathophysiological role of vitamin C in these patients. METHODS:
      We studied 58 patients and evaluated the relationship between renal function and
      plasma vitamin C concentration, as well as the effect of diabetes on this
      relationship. Endothelium-dependent flow-mediated dilation of brachial artery was
      measured to assess the endothelial function. Serum malondialdehyde low-density
      lipoprotein was measured as a marker for oxidative stress. RESULTS: Plasma
      vitamin C concentration had a positive linear relationship with eGFR in both
      diabetic and non-diabetic patients (P = 0.006 and P = 0.004, respectively). When
      vitamin C concentration and eGFR relationships were compared in the two groups,
      vitamin C concentration was significantly lower in diabetic patients at every
      eGFR (P = 0.006). Flow-mediated vasodilatation of the brachial artery was
      positively correlated with vitamin C concentration in non-diabetic patients (P =
      0.047) but not in diabetic patients. There was a negative correlation between
      serum malondialdehyde low-density lipoprotein and vitamin C concentration in non
      diabetic patients (P = 0.044) but not in diabetic patients. CONCLUSIONS: Renal
      dysfunction was associated with a decrease in plasma vitamin C level. Moreover,
      decreased vitamin C may cause endothelial dysfunction via an increase in
      oxidative stress in non-diabetic chronic kidney disease patients.

PMID- 20817672
TI  - Tachycardia as a predictor of poor survival in chronic haemodialysis patients.
AB  - BACKGROUND: High pulse rate is a culprit of all causes of death in the general
      population, but its relation to death in haemodialysis (HD) patients has not been
      examined in a large patient cohort. METHODS: We examined the relationship between
      pulse rate (beats per minute, bpm) before an HD session and survival based on the
      nationwide HD registry of the Japanese Society for Dialysis Therapy. Outcomes
      were confirmed using the coded ID numbers of both 2005 and 2006 registries.
      Logistic analyses were performed to determine the effect of pre-HD pulse rate on
      survival. A total of 147,702 patients (50.5% men; 31.4% with diabetes mellitus;
      mean age 63.6 years) on HD three times weekly were studied. Mean (SD) pulse rate
      was 74.6 (12.0) bpm. RESULTS: The pulse rate distribution was as follows: 0.7%
      (40-49 bpm), 6.1% (50-59 bpm), 25.3% (60-69 bpm), 38.1% (70-79 bpm), 18.7% (80-89
      bpm), 7.9% (90-99 bpm), 2.4% (100-109 bpm) and 0.7% (110-129 bpm). Overall 1-year
      mortality rate was 6.6%. Compared with the reference pulse rate (60-69 bpm), the
      odds ratio (95% CI) for 1-year mortality was 1.20 (0.88-1.63, NS: 40-49 bpm),
      1.06 (0.93-1.21, NS: 50-59 bpm), 1.13 (1.04-1.22, P = 0.0037: 70-79 bpm), 1.46
      (1.33-1.60, P < 0.0001: 80-89 bpm), 1.91 (1.70-2.15, P < 0.0001: 90-99 bpm), 2.61
      (2.19-3.10, P < 0.0001: 100-109 bpm), and 2.43 (1.79-3.30, P < 0.0001: 110-129
      bpm) after adjusting for age, sex, diabetes mellitus, body mass index, HD
      duration, serum albumin, haemoglobin, systolic blood pressure, medication for
      hypertension, and history of acute myocardial infarction. CONCLUSIONS: Survival
      rate decreased with an increase in the pre-HD pulse rate in chronic HD patients.
      The causality of this association and the reasons for a better annual mortality
      rate of 6.6% remain to be clarified.

PMID- 20817673
TI  - Successful transplantation of a donor kidney with diffuse proliferative lupus
      nephritis and crescents--a case report.
AB  - Pre-existing diffuse proliferative glomerulonephritis (DPGN) in a potential
      deceased kidney donor has been considered a contraindication for transplantation.
      We report a case of a patient who underwent a successful deceased donor renal
      transplantation from a donor with history of systemic lupus erythematosus (SLE)
      whose baseline biopsy revealed DPGN. Although the histology was relatively benign
      in the procurement kidney biopsy done by frozen section, the final light
      microscopy available after transplantation showed diffuse proliferative lupus
      nephritis, WHO class IV, with 44% crescents. The post-transplant course was
      complicated by delayed allograft function requiring haemodialysis for the first
      week. A repeat biopsy performed after 4 months of transplant showed resolution of
      the proliferative lesions in the glomeruli with disappearance of the crescents.
      At 5.5 years of follow-up, the patient's creatinine has been stable at 2.0 mg/dL
      (176.8 MUmol/L), but he has persistent proteinuria.

PMID- 20817671
TI  - Early change in proteinuria as a surrogate outcome in kidney disease progression:
      a systematic review of previous analyses and creation of a patient-level pooled
      dataset.
AB  - BACKGROUND: Proteinuria is a candidate surrogate end point for randomized
      controlled trials (RCTs) in chronic kidney disease (CKD). There is a reasonably
      sound biological basis for this hypothesis, but only preliminary empirical
      evidence currently exists. METHODS: A systematic review and creation of a patient
      level dataset of randomized controlled trials (RCTs) in CKD that reported changes
      in proteinuria and assessed progression of kidney disease as defined by dialysis,
      transplantation, death, or changes in GFR or creatinine were performed. RESULTS:
      Systematic review. Seventy RCTs met the eligibility criteria; 17 eligible RCTs
      contained analyses of proteinuria as a predictor of outcomes; 15 RCTs concluded
      that greater proteinuria was associated with adverse outcomes. A majority were
      studies of diabetic or hypertensive kidney disease and tested renin-angiotensin
      system blockade. Definitions of predictor and outcome variables were too variable
      to conduct a meta-analysis of group data. Database creation. Over 4 years was
      required to create the patient-level dataset. The final dataset included 34
      studies and > 9000 patients with a variety of CKD types and interventions.
      CONCLUSIONS: There are a relatively small number of RCTs designed to rigorously
      test therapies for kidney disease progression. Current analyses of change in
      proteinuria as a predictor of CKD progression are heterogeneous and incomplete,
      indicating further evaluation in a pooled individual patient-level database is
      necessary to advance knowledge in this field.

PMID- 20817674
TI  - Luteolin ameliorates cisplatin-induced acute kidney injury in mice by regulation
      of p53-dependent renal tubular apoptosis.
AB  - BACKGROUND: Cisplatin chemotherapy often causes acute kidney injury in cancer
      patients. The causative mechanisms of cisplatin-induced acute kidney injury
      include renal inflammation, activation of p53 tumour suppressor protein and
      tubular apoptosis. Luteolin, a flavone found in medicinal herbs and plants, has
      been reported to exhibit anti-inflammatory, antioxidant and anticarcinogenic
      activities. The purpose of this study was to investigate the anti-apoptotic
      effect of luteolin on cisplatin-induced acute kidney injury and the molecular
      mechanism. METHODS: C57BL/6 mice were treated with cisplatin (20 mg/kg) with or
      without treatment with luteolin (50 mg/kg for 3 days). Renal function,
      histological changes, degree of oxidative stress and tubular apoptosis were
      examined. The effects of luteolin on cisplatin-induced expression of renal p53,
      PUMA-alpha and Bcl-2 family proteins were evaluated. RESULTS: Treatment of mice
      with cisplatin resulted in renal damage, showing an increase in blood urea
      nitrogen and creatinine levels, tubular damage, oxidative stress and apoptosis.
      Treatment of cisplatin-treated mice with luteolin significantly improved renal
      dysfunction, reducing tubular cell damage, oxidative stress and apoptosis.
      Examination of molecules involving apoptosis of the kidney revealed that
      treatment of cisplatin increased the levels of p53 and its phosphorylation, PUMA
      alpha, Bax and caspase-3 activity that were significantly decreased by treatment
      with luteolin. CONCLUSION: These results indicate that cisplatin induces acute
      kidney injury by regulation of p53-dependent renal tubular apoptosis and that
      luteolin ameliorates the cisplatin-mediated nephrotoxicity through down
      regulation of p53-dependent apoptotic pathway in the kidney.

PMID- 20817675
TI  - Genome-wide binding profiles of the Bacillus subtilis transition state regulator
      AbrB and its homolog Abh reveals their interactive role in transcriptional
      regulation.
AB  - AbrB is a global transcriptional regulator of Bacillus subtilis that represses
      the expression of many genes during exponential growth. Here, we demonstrate that
      AbrB and its homolog Abh bind to hundreds of sites throughout the entire B.
      subtilis genome during exponential growth. Comparison of regional binding of AbrB
      and Abh in wild-type, DeltaabrB and Deltaabh backgrounds revealed that they bind
      as homomer and/or heteromer forms with different specificities and affinities. We
      found four AbrB and Abh binding patterns were major. Three of these contain pairs
      of TGGNA motifs connected by A/T-rich sequences, differing in arrangement and
      spacing. We also assessed the direct involvement of these complexes in the
      control of gene expression. Our data indicate that AbrB usually acts as a
      repressor, and that the ability of Abh to act as a transcriptional regulator was
      limited. We found that changes to AbrB/Abh levels affect their binding at several
      promoters and consequently transcriptional regulation. Surprisingly, most
      AbrB/Abh binding events had no impact on transcription, suggesting an interesting
      possibility that AbrB/Abh binding is analogous to nucleoid-associated protein
      binding in Escherichia coli.

PMID- 20817676
TI  - Human single-nucleotide polymorphisms alter p53 sequence-specific binding at gene
      regulatory elements.
AB  - p53 coordinates the expression of an intricate network of genes in response to
      stress signals. Sequence-specific DNA binding is essential for p53-mediated tumor
      suppression. We evaluated the impact of single-nucleotide polymorphisms (SNPs) in
      p53 response elements (p53RE) on DNA binding and gene expression in response to
      DNA damage. Using a bioinformatics approach based on incorporating p53 binding
      strength into a position weight matrix, we selected 32 SNPs in putative and
      validated p53REs. The microsphere assay for protein-DNA binding (MAPD) and allele
      specific expression analysis was employed to assess the impact of SNPs on p53-DNA
      binding and gene expression, respectively. Comparing activated p53 binding in
      nuclear extracts from doxorubicin- or ionizing radiation (IR)-treated human
      cells, we observed little difference in binding profiles. Significant p53 binding
      was observed for most polymorphic REs and several displayed binding comparable to
      the p21 RE. SNP alleles predicted to lower p53 binding indeed reduced binding in
      25 of the 32 sequences. Chromatin immunoprecipitation-sequencing in
      lymphoblastoid cells confirmed p53 binding to seven polymorphic p53 REs in
      response to doxorubicin. In addition, five polymorphisms were associated with
      altered gene expression following doxorubicin treatment. Our findings demonstrate
      an effective strategy to identify and evaluate SNPs that may alter p53-mediated
      stress responses.

PMID- 20817677
TI  - The cyclin-dependent kinase inhibitor p21 is regulated by RNA-binding protein
      PCBP4 via mRNA stability.
AB  - RNA-binding proteins (RBPs) play a major role in many post-transcriptional
      processes, including mRNA stability, alternative splicing and translation. PCBP4,
      also called MCG10, is an RBP belonging to the poly(C)-binding protein family and
      a target of p53 tumor suppressor. Ectopic expression of PCBP4 induces cell-cycle
      arrest in G2 and apoptosis. To identify RNA targets regulated by PCBP4 and
      further decipher its function, we generated multiple cell lines in which PCBP4 is
      either inducibly over-expressed or knocked down. We found that PCBP4 expression
      decreases cyclin-dependent kinase inhibitor p21 induction in response to DNA
      damage. We also provided evidence that PCBP4 regulates p21 expression
      independently of p53. In addition, we showed that a deficiency in PCBP4 enhances
      p21 induction upon DNA damage. To validate PCBP4 regulation of p21, we made PCBP4
      deficient mice and showed that p21 expression is markedly increased in PCBP4
      deficient primary mouse embryo fibroblasts compared to that in wild-type
      counterparts. Finally, we uncovered that PCBP4 binds to the 3'-UTR of p21
      transcript in vitro and in vivo to regulate p21 mRNA stability. Taken together,
      we revealed that PCBP4 regulates both basal and stress-induced p21 expression
      through binding p21 3'-UTR and modulating p21 mRNA stability.

PMID- 20817678
TI  - Acute laryngotracheitis after accidental aspiration of clindamycin.

PMID- 20817679
TI  - Managing anaemia in critically ill adults.

PMID- 20817680
TI  - UK hip fracture audit shows wide variation in standards of care.

PMID- 20817681
TI  - Dutch medical associations support freezing oocytes for non-medical reasons.

PMID- 20817682
TI  - Body composition and metabolic syndrome in patients with primary gout in Vietnam.
AB  - OBJECTIVE: To characterize the body composition, to determine the prevalence of
      metabolic syndrome (MetS), and to examine the association between body
      composition and the components of MetS in Vietnamese patients with primary gout.
      METHODS: A total of 107 males with gout and 107 age-matched healthy males
      underwent physical examination, body composition assessment by dual-energy X-ray
      absorptiometry and blood tests. Both the original and revised National
      Cholesterol Education Program Adult Treatment Panel (NCEP/ATP) III criteria were
      used to define MetS. RESULTS: Means of total body and trunk fat mass in patients
      with gout were higher (P<0.001) than those in controls: 20.9 vs 13.3 kg and 11.4
      vs 6.1 kg, respectively. The prevalence of MetS according to the original and
      revised NCEP/ATP III criteria in patients with gout was also higher (P<0.001)
      than in controls (33.6 vs 15.9% and 56.1 vs 23.4%), respectively. In patients
      with gout, total fat mass was strongly correlated with BMI (r=0.86, P<0.001),
      while trunk fat mass was strongly correlated with waist circumference (r=0.91,
      P<0.001). Total fat mass, trunk fat mass and trunk fat mass/legs fat mass ratio
      were positively correlated (P<0.05) with glycaemia, triglyceridaemia, blood
      pressure and negatively correlated (P<0.05) with high-density liproprotein
      cholesterol levels. CONCLUSION: Patients with gout had significantly higher fat
      mass, especially in the trunk region, and higher prevalence of MetS than healthy
      controls. Therefore, management of weight and MetS should be emphasized in
      patients with gout to reduce their risk of cardiovascular diseases.

PMID- 20817683
TI  - Maintaining the competence of Europe's workforce.

PMID- 20817685
TI  - A community pharmacist delivered adherence support service for dyslipidaemia.
AB  - BACKGROUND: Dyslipidaemia is a major risk factor for coronary heart disease. A
      key issue in management is adherence to therapy. Pharmacists are ideally situated
      to provide a service to increase medication adherence and optimize health
      outcomes. This study aimed to evaluate the impact of a community pharmacist
      delivered adherence support service on patients' adherence and total cholesterol
      levels. METHODS: A repeated measures [baseline (t = 1), post-intervention at 3
      monthly intervals (t = 2,3,4)], randomized-controlled study in community
      pharmacies, with patients on chronic lipid-lowering therapy was conducted.
      Measures used were Brief Medication Questionnaire, Medication Adherence Report
      Scale, total cholesterol and pharmacist intervention data sheets. A baseline t
      test of cholesterol levels between groups was conducted followed by a repeated
      measures analysis of variance. RESULTS: Seventeen pharmacists recruited 142
      patients (97 completions: 49 control, 48 intervention). Most patients missed
      either the third or last visit, thus data at t = 3 and 4 were combined. Although
      the intervention group started with a higher cholesterol level (5.1 vs. 4.8
      mmol/l), a difference was observed in the drop in cholesterol levels of the
      intervention group between t = 2 and 3 (F(1,95) = 8.85, P < 0.01), and between
      the two groups over the study period (F(2,190) = 4.89, P < 0.05). No changes in
      medicine adherence scores were observed though there was an improvement in
      participants' exercise and eating habits. CONCLUSIONS: Patients significantly
      lowered their cholesterol levels probably as a result of the service delivered by
      their pharmacists within the short study time frame of ~9 months.

PMID- 20817687
TI  - Exploring the role of economics in prioritization in public health: what do
      stakeholders think?
AB  - BACKGROUND: Debates surrounding the use of conventional approaches in public
      health and the existence of perceived barriers to using the results of economic
      evaluations have led to questions posed as to how to establish priorities within
      public health schemes. The aims of this study were therefore to explore the
      feasibility and validity of economic evaluation techniques in developing
      priorities within public health programmes and consider the extent to which
      different presentational approaches are likely to be incorporated into decision
      making, from perspectives of relevant stakeholders. METHODS: An advisory board,
      representative of potential users of economic evaluations, was set up to identify
      preferences for how findings from economic evaluations might be presented to
      decision makers and to test the impact of different approaches, different outputs
      and different presentational styles. The board was divided into two groups, each
      of which was given three hypothetical 'scenarios' to consider. The scenarios
      comprised descriptions of methods and outputs, with costs, effects, target
      population and context of intervention constant across all scenarios. RESULTS:
      The perceived validity of estimates of effectiveness was vitally important, along
      with sufficient information to gauge whether designs were appropriate and to
      assess implementation practicalities. Cost-benefit analysis and cost-utility
      analysis were the preferred approaches despite their complexity, although
      participants required benchmarks to place net-benefit estimates from cost-benefit
      analyses into context. CONCLUSION: Further research is required to substantiate
      and build on these preliminary findings and collaborations between economists and
      policy makers are needed to develop clear, rigorous and standard guidance
      relating to economic evaluation, recognizing the diversity of public health
      strategies.

PMID- 20817688
TI  - European survey of hepatitis B vaccination policies for healthcare workers.
AB  - BACKGROUND: The risk of transmission of hepatitis B virus (HBV) to healthcare
      workers (HCWs) is well known. Under current European Union (EU) legislation, all
      employers should perform a risk assessment to identify those exposed to HBV and
      offer vaccination. Immunization should happen early after the start of their
      career to avoid infection and development of carrier status. METHODS: Cross
      sectional survey of country representatives, to find out how policies are put
      into practice in European countries. RESULTS: Answers were received from 17
      countries, representing 89% of the population and 90% of HCWs in the EU-25. HBV
      vaccination was mandatory for medical, and nursing and other paramedical staff in
      five countries, and recommended in all other countries. It was mandatory for
      medical students and student nurses in five countries and recommended in nine
      other. Pre-vaccination serotesting was done in six countries. The vaccination
      schedule most often used was 0, 1, 6 months. Combined vaccine (hepatitis A virus
      /HBV) was used in 10 countries. Post-vaccination serotesting was done in 14
      countries. Data on HBV vaccination coverage were available in 11 countries and
      published in five of them. Coverage was 85-93%. CONCLUSION: These results show
      the variation as to how EU legislation is translated into practice in European
      countries. More consultation between key actors at EU level could help to
      optimize the way this matter is dealt with. A battery of measures and
      interventions-including introduction of immunization programmes against HBV
      infection and increasing immunization coverage in HCWs-can contribute to further
      reducing HBV transmission to HCWs.

PMID- 20817689
TI  - Evidence behind the WHO guidelines: hospital care for children: what is the
      diagnostic accuracy of gastric aspiration for the diagnosis of tuberculosis in
      children?

PMID- 20817690
TI  - Who and where are the children yet to enroll in Medicaid and the children's
      health insurance program?
AB  - Kathleen Sebelius, secretary of health and human services, has issued a challenge
      to enroll the millions of uninsured children eligible for public insurance in
      Medicaid or the Children's Health Insurance Program (CHIP). This paper provides
      estimates of the rates at which children in the various states participated in
      these programs in 2008 as well as the number who were eligible for them but
      uninsured. According to our coverage estimates, an estimated 7.3 million children
      were uninsured on an average day in 2008, of whom 4.7 million (65 percent) were
      eligible for Medicaid or CHIP but not enrolled. Participation rates varied across
      states from 55 percent to 95 percent, and ten states had participation rates
      close to or above 90 percent. Thirty-nine percent of eligible uninsured children
      (1.8 million) live in just three states--California, Texas, and Florida--and 61
      percent (2.9 million) live in ten states. Meeting Secretary Sebelius's challenge
      means achieving success in these populous states, in part through tools and
      resources available under the 2009 CHIP reauthorization law.

PMID- 20817691
TI  - Rising to the challenge: tools for enrolling eligible children in health
      coverage.
AB  - Nearly five million uninsured children in the United States are currently
      eligible for Medicaid or the Children's Health Insurance Program (CHIP) but are
      not enrolled in these programs. A top Obama administration priority is to achieve
      the long-sought goal of ensuring that uninsured children are enrolled--and that
      they stay enrolled for as long as they are eligible. The author, who is secretary
      of the U.S. Department of Health and Human Services (HHS), outlines measures that
      HHS and other federal agencies are implementing to reach this goal. She also
      cites existing state efforts to enroll more children and improve children's
      coverage, and she describes steps that states, local governments, and the private
      sector can take to expand outreach efforts, increase enrollment, and keep
      eligible children covered.

PMID- 20817692
TI  - Left ventricular twist: comparison between two- and three-dimensional speckle
      tracking echocardiography in healthy volunteers.
AB  - AIMS: left ventricular (LV) twist is the result of clockwise rotation of the base
      and counterclockwise rotation of the apex. The aims of this study were to
      investigate the feasibility of the three-dimensional speckle-tracking
      echocardiography (3DSTE) to assess LV twist values and compare the data measured
      by two-dimensional speckle-tracking echocardiography (2DSTE) in a group of
      healthy volunteers. METHODS AND RESULTS: fifty individuals were enrolled in the
      protocol. LV twist was defined as net difference between averaged 2DSTE apical (4
      segments) and basal (6 segments) rotations. 3DSTE twist was obtained from the LV
      volumetric image and shown as the averaged global value of 16 segments. Time-to
      peak by both techniques was also measured and compared. Significant differences
      between the two techniques were calculated using the paired Student t-test. P
      values of <0.05 were considered significant. Reliable LV twist measurement was
      possible in 39 of 50 individuals (78%). 2DSTE twist mean peak value was 13.8 +
      7.9 degrees  with a mean time-to-peak of 388.3 +/- 152.3 ms and global 3DSTE
      twist mean peak value was 10.2 + 7.6 degrees  with a mean time-to-peak of 371.8
      +/- 127.5 ms. Peak LV twist values by 3DSTE was significantly smaller than by
      2DSTE (P < 0.01) whereas time-to-peak results showed no significant difference.
      CONCLUSION: 3DSTE is feasible to assess LV twist deformation. Whereas further
      investigations using 3DSTE are needed to validate this promising technology,
      comparing 2DSTE and 3DSTE should be done with caution, as values for peak LV
      twist differ.

PMID- 20817693
TI  - Echocardiography without electrocardiogram.
AB  - AIMS: automatic detection of the QRS complex on electrocardiogram (ECG) is used
      on cardiac ultrasound scanners to separate ultrasound image series into cardiac
      cycles for playback and storage. On small hand-held scanners it is unpractical to
      connect ECG cables. We therefore aim to do automatic cardiac cycle separation
      using apical B-mode ultrasound images. METHODS AND RESULTS: cardiac cycle length
      is estimated by cyclicity analysis of B-mode intensities. To determine a cycle
      start estimate near QRS, a deformable model is fitted to the left ventricle in
      real-time. The model is used to initialize and constrain a speckle tracker
      positioned near the mitral annulus. In the displacement curve generated by the
      speckle tracker, a time point near maximum distance from the probe is detected as
      a cardiac cycle start estimate. Validation against ECG was done on 233 recordings
      from normal subjects and 46 recordings from subjects with coronary pathology.
      Several test cases were run for each recording to emulate B-mode series starting
      at all time points in the cardiac cycle. Totally, 11 886 test cases were run.
      Cycle length estimation was feasible in 98% of normal subject cases and 91% of
      pathology cases. Median difference in cycle length by ECG was 0 and -3 ms,
      respectively. Cycle start estimation was feasible in 90% of normal subject cases
      and 77% of pathology cases. Median difference to cycle start by ECG was 62 and 76
      ms, respectively. CONCLUSION: apical B-mode series can automatically be separated
      into cardiac cycles without using ECG.

PMID- 20817694
TI  - Tumourigenesis in the infarcted rat heart is eliminated through differentiation
      and enrichment of the transplanted embryonic stem cells.
AB  - AIMS: The therapeutic potential of embryonic stem cells (ESCs) in ischaemic heart
      disease has been widely explored. However, tumourigenesis upon implantation
      interferes with the clinical application of ESC transplantation. This study aims
      to evaluate the influence of differentiation and enrichment of transplanted ESCs
      on tumourigenesis in infarcted rat hearts. METHODS AND RESULTS: Mouse ESCs
      (mESCs) were cultured using a bioreactor system to develop embryoid bodies, which
      were then induced with 1% ascorbic acid to differentiate into cardiomyocytes. The
      mESCs-derived cardiomyocytes (mESCs-CMs) were enriched by Percoll density
      gradient separation. The specific markers (OCT-4, Sox2, and Nanog) of
      undifferentiated ESCs were detected by PCR both in mESCs and in mESCs-CMs, but
      not in the mESC-derived Percoll-enriched cardiomyocytes (mESC-PE-CMs).
      Immunosuppressed rats with infarcted hearts were randomly injected with the
      mESCs, mESC-CMs, or mESC-PE-CMs. Eight weeks after cell transplantation,
      histological and immunohistochemical analysis showed that the transplantation of
      both mESCs and mESC-CMs caused the formation of teratomas. The incidence of
      teratoma was markedly lower (P < 0.05) in the mESC-CMs group than in the mESCs
      group. The average tumour volume was significantly lower (P < 0.05) in the mESC
      CMs group than in the mESCs group. Tumour formation was absent in the mESC-PE-CMs
      group. CONCLUSION: Enrichment of the mESC-differentiated cardiomyocytes inhibited
      the development of teratoma after cell transplantation in the infarcted rat
      hearts. These findings offer a new strategy for eliminating teratoma formation in
      ESCs transplantation and could be a step forward in the development of human ESCs
      transplantation therapy in ischaemic heart disease.

PMID- 20817695
TI  - Prognostic value of endothelial microparticles in patients with heart failure.
AB  - AIMS: Heart failure (HF) is associated with endothelial dysfunction. Endothelium
      derived microparticles (EMPs) are a novel quantitative plasma marker of
      endothelial dysfunction. We investigated whether plasma levels of EMPs can
      predict future cardiovascular events in patients with HF. METHODS AND RESULTS: We
      enrolled 169 consecutive HF patients (70 ischaemic, 99 non-ischaemic HF) with New
      York Heart Association (NYHA) class I or more. Plasma CD144-positive EMP levels
      were measured by flow cytometry in the HF patients and in 31 healthy subjects. We
      followed the HF patients for mean 30 months. Endpoints were: a composite of
      cardiovascular events (myocardial infarction, stroke, re-hospitalization for HF,
      and cardiovascular death) and all-cause mortality. Endothelium-derived
      microparticle levels increased significantly with NYHA functional class [EMP
      median (range): healthy, 0.325 (0.164-0.354) *106/mL; NYHA I, 0.484 (0.426
      0.575); II, 0.646 (0.439-0.795); and III/IV, 0.786 (0.569-1.026), P < 0.001]. A
      total of 33 cardiovascular events and 22 all-cause deaths were registered. Kaplan
      Meier analysis demonstrated a significantly higher probability of cardiovascular
      events in the high-EMP group, but there was only a borderline difference for all
      cause mortality (above median; log rank test P = 0.01, P = 0.053, respectively).
      Multivariate Cox regression analysis adjusted for clinical factors, identified
      high-EMP levels as an independent predictor of future cardiovascular events, but
      not for all-cause mortality in HF patients [hazard ratio (95% confidence
      interval): 2.423 (1.034-5.681), P = 0.04 for cardiovascular events; and 2.095
      (0.825-5.323), P = 0.12 for all-cause mortality]. CONCLUSION: Endothelial
      dysfunction assessed by plasma levels of EMPs can independently predict future
      cardiovascular events in patients with HF. Endothelium-derived microparticles are
      a potentially useful biomarker of endothelial dysfunction in HF risk
      stratification.

PMID- 20817696
TI  - Subjective measures of socio-economic position and the wealth index: a
      comparative analysis.
AB  - INTRODUCTION: The wealth index is a commonly-used measure of socio-economic
      position (SEP) in low- and middle-income settings, but there is concern that it
      is strongly influenced by community-level as well as household-level factors.
      Subjective SEP indicators are infrequently used in health research. METHODS: We
      use data from 11 280 households included in the Malawi Integrated Household
      Survey 2004/5. We compare the wealth index with four subjective measures of SEP:
      perceived food consumption adequacy, perceived overall consumption adequacy, an
      economic ladder question, and perceived income sufficiency. The wealth index is
      compared with each subjective SEP measure in terms of: (i) agreement of
      classification of households, (ii) targeting accuracy with respect to US$1-a-day
      poverty based on consumption expenditure, and (iii) the socio-economic processes
      (household- and community-level) giving rise to the SEP scores. RESULTS: Each
      subjective SEP indicator resulted in considerable differential classification of
      households compared with the wealth index. Three measures of subjective SEP
      (perceived food consumption adequacy, economic ladder question, and perceived
      income sufficiency) identified a higher proportion of dollar-a-day poor
      households as poor than the wealth index. The wealth index was strongly
      influenced by community infrastructure, but all subjective SEP indicators were
      free from strong community-level influence. CONCLUSION: The strengths and
      limitations of any measure of SEP depend on the context and purpose for which it
      is being used. In these data, the wealth index was strongly influenced by
      community infrastructure, whereas the subjective SEP measures were not, perhaps
      allowing analyses using them to disentangle household and community influences.
      Several subjective measures also corresponded to dollar-a-day poverty more
      strongly than the wealth index. Subjective measures may therefore be preferable
      to the wealth index in some circumstances, although they have their own set of
      potential biases.

PMID- 20817697
TI  - Prospects for regulated competition in the health care system: what can China
      learn from Russia's experience?
AB  - As China explores new directions to reform its health care system, regulated
      competition among both insurers and providers of care might be one potential
      model. The Russian Federation in 1993 implemented legislation intended to
      stimulate such regulated competition in the health care sector. The subsequent
      progress and lessons learned over these 17 years can shed light on and inform the
      future evolution of the Chinese system. In this paper, we list the necessary pre
      conditions for reaping the benefits of regulated competition in the health care
      sector. We indicate to what extent these conditions are being fulfilled in the
      post-reform Russian and current Chinese health care systems. We draw lessons from
      the Russian experience for the Chinese health care system, which shares a similar
      economic and political background with the pre-reform Russian health care system
      in terms of the starting point of the reform, and analyse the prospects for
      regulated competition in China.

PMID- 20817698
TI  - Opa1 deficiency in a mouse model of dominant optic atrophy leads to retinal
      ganglion cell dendropathy.
AB  - The heterozygous mutation B6;C3-Opa1(Q285STOP), which models autosomal dominant
      optic atrophy, leads to a 50% reduction in Opa1 transcript and protein in the
      mouse retina and neural tissues and is associated with visual dysfunction and
      structural changes in the murine retina and optic nerve. In this article we use
      this model to quantify and evaluate the dendritic morphology of retinal ganglion
      cells. Retinal ganglion cells in Opa1(+/-) mutant mice (n=16) and accompanying
      age- and sex-matched controls (n=11) (age ranges of <10, 10-15 and >20 months)
      were labelled DiOlistically with carbocyanine dyes to quantify changes in
      dendritic tree architecture as a function of age. We observed localized dendritic
      reduction to sublamina b of the inner plexiform layer without retinal ganglion
      cell loss, showing dendritic pruning of on- but not off-centre retinal ganglion
      cells, and this effect was exacerbated with age. The mean dendritic field area
      was reduced in on-centre retinal ganglion cells of 10- to 15-month-old mice (
      24.24%; C(V) =0.68; P<0.05) and >20-month-old mice (-43.22%; C(V) =0.75; P<0.05)
      compared with age-matched wild-type controls. Similar changes were seen in
      average total dendritic length in on-centre retinal ganglion cells of 10- to 15
      month-old mice (-31.66%; C(V) =0.67; P<0.05) and >20-month-old mice (-49.55%;
      C(V) =0.63; P<0.05). Sholl analysis showed a marked difference in the dendritic
      arborization of on-centre retinal ganglion cells in the 10- to 15-month-old group
      (area under the curve -21.67%; P>0.05) and of the >20-month-old group (area under
      the curve -42.12%; P<0.05) compared with the control group. There was no
      detectable change in dendritic morphology in <10-month-old Opa1(+/-) mutant mice
      compared with wild-type (P>0.05). No significant changes (P>0.05) were seen in
      off-centre retinal ganglion cells. Finally, there was also no significant change
      (P>0.05) in the retinal ganglion cell count across all age groups. In conclusion,
      we show dendritic pruning in on-centre retinal ganglion cells of the Opa1(+/-)
      mouse model of autosomal dominant optic atrophy from as early as 10 months of
      age. These results highlight the importance of normal mitochondrial fusion
      balance, as influenced by the OPA1 protein in maintaining the dendritic
      morphology of retinal ganglion cells. Dendritic pruning precedes the onset of
      clinical visual loss and structural changes in the optic nerve in the absence of
      significant cell loss.

PMID- 20817699
TI  - Health status of residents of an urban dual reticulation system.
AB  - BACKGROUND: Households in dual reticulation developments are supplied with
      recycled water from sewage effluent for some non-potable purposes, and
      conventional tap water for other uses. Adverse health effects from recycled water
      exposure are considered unlikely; however, no epidemiological studies have been
      undertaken to assess the public health impact of such exposures. METHODS: We
      compared the health status of residents of a dual reticulation housing
      development with residents of an adjacent conventional water supply area by
      assessing consultation rates with primary-care physicians for three conditions
      considered plausibly related to recycled water exposure (gastroenteritis,
      respiratory complaints and dermal complaints), and two conditions considered
      unrelated to water exposures (urinary tract infections and musculoskeletal
      complaints). RESULTS: We found little difference in the overall number of medical
      consultations per person, or in consultation rates for specific disease
      conditions between residents of the two water supply areas, after adjustment for
      demographic differences. Slight elevations in odds ratios (ORs) for dermal and
      respiratory consultations were observed, but seasonal patterns were not
      consistent with recycled water exposures. CONCLUSIONS: This retrospective
      assessment of medical records indicates that residents of the dual reticulation
      water supply area are not likely to be experiencing elevated rates of adverse
      health outcomes as a result of their exposure to recycled water. This finding
      provides added assurance that appropriately operated and managed dual
      reticulation residential developments are a safe option for future urban water
      supplies.

PMID- 20817700
TI  - Carbon monoxide uptake kinetics of arterial, venous and capillary blood during CO
      rebreathing.
AB  - The uptake and distribution of CO throughout the circulatory system during two
      different methods of CO rebreathing (2 min 'Schmidt' and 40 min 'Burge' methods)
      were determined in nine healthy volunteers. Specifically, the impact of (i)
      differences in circulatory mixing time (t(mix)), (ii) CO diffusion to myoglobin
      (Mb) and (iii) CO wash-out was assessed on calculated haemoglobin mass
      (Hb(mass)). Arterial (a), muscle venous (vm) and capillary samples (c) were
      obtained simultaneously at 0, 1, 2, 3.5, 5, 7.5, 10, 12.5, 15, 20, 30 and 40 min
      for determination of carboxyhaemoglobin (HbCO). Carbon monoxide wash-out was
      measured from expired air following rebreathing. The rate of CO diffusion to Mb
      was calculated using the change in HbCO after t(mix), and the rate of CO wash
      out. In both methods, HbCOa and HbCOc followed a near-identical time course,
      peaking within the first 2 min and decreasing thereafter. The HbCOvm increased
      slowly and was significantly lower at 1, 2 and 3.5 min in both methods (P <
      0.01). The HbCOa peaked significantly higher in the Schmidt method (P = 0.03).
      Circulatory mixing had occurred by 10 min in most but not all subjects. The rate
      of CO wash-out was 0.25 +/- 0.13 ml min-1 in the Schmidt and 0.25 +/- 0.16 ml min
      1 in the Burge method. The rate of CO diffusion to Mb was 0.22 +/- 0.11 and 0.16
      +/- 0.13 ml min-1 (P = 0.63) in Schmidt and Burge methods, respectively.
      Inhalation of a CO bolus during the Schmidt method results in faster HbCOa uptake
      but does not greatly shorten t(mix) or influence rates of CO wash-out and flux to
      Mb. The calculated Hb(mass) depends substantially on the plateau level of HbCO;
      therefore, it is paramount to ensure HbCO is mixed completely prior to blood
      sampling, as well as accounting for potential within-subject alterations of CO
      exhalation and CO flux to Mb.

PMID- 20817701
TI  - Acetylcholine acutely modifies nitric oxide synthase function in the human
      coronary circulation.
AB  - Intracoronary infusions of acetylcholine (ACh) and the nitric oxide synthase
      (NOS) inhibitor N(G)-monomethyl-l-arginine (l-NMMA) are routinely used to assess
      endothelial function in the human coronary circulation. Currently, there are no
      studies that examine whether the response to one of these agents predicts the
      response to the other in a given individual. We sought to determine whether human
      coronary vasomotor responses to intracoronary ACh are predictive of the response
      to intracoronary l-NMMA. Following diagnostic coronary angiography, a coronary
      sinus catheter was placed. Sequential intracoronary infusions of ACh and l-NMMA
      were performed in 14 patients without severe coronary artery disease (CAD). In
      nine patients with severe CAD, only l-NMMA was infused. Quantitative coronary
      angiography was performed immediately following infusions to determine changes in
      coronary diameter. Coronary sinus oxygen saturation and the transcardiac oxygen
      saturation gradients were determined during infusions as an index of coronary
      blood flow (CBF). There were no significant differences in the prevalence of
      hypertension, diabetes, smoking or plasma creatinine or cholesterol levels
      between patients with and without severe CAD. In the 14 patients without severe
      CAD, ACh reduced coronary diameter on average by 8% (from 2.7 +/- 0.8 to 2.5 +/-
      0.8 mm, P = 0.003) and reduced the transcardiac oxygen saturation gradient from
      63 +/- 8 to 42 +/- 16% (P = 0.0001). N(G)-Monomethyl-l-arginine had no
      significant effect on coronary diameter (from 2.7 +/- 0.8 to 2.7 +/- 0.8 mm,
      n.s.) and did not alter the transcardiac oxygen saturation gradient (from 63 +/-
      8 to 63 +/- 7%, n.s.). A positive rather than negative correlation was observed
      between the ACh- and l-NMMA-induced changes in coronary diameter (r = 0.752, P =
      0.0002). In nine patients with severe CAD who did not receive ACh, l-NMMA had no
      effect on coronary diameter but produced an increased transcardiac oxygen
      saturation gradient consistent with reduced CBF (from 58 +/- 5 to 62 +/- 4%, P =
      0.003). The CBF response to l-NMMA was significantly different between the two
      groups (P = 0.002). The failure of l-NMMA to reduce CBF following ACh infusion,
      in contrast to the results seen in the l-NMMA-only group, suggests that NOS had
      been rendered dysfunctional by the ACh infusion itself. The positive correlation
      in changes to coronary diameter between ACh and l-NMMA suggests that the degree
      of NOS dysfunction was directly correlated to the degree of preceding activation
      by ACh. Combined, these unexpected results suggest that ACh administration may
      acutely modify the function of NOS in the human coronary circulation.

PMID- 20817702
TI  - Composite anatomical-clinical-molecular prognostic model in non-small cell lung
      cancer.
AB  - The objective of the present study was to elaborate a survival model that
      integrates anatomic factors, according to the 2010 seventh edition of the tumour,
      node and metastasis (TNM) staging system, with clinical and molecular factors.
      Pathologic TNM descriptors (group A), clinical variables (group B), laboratory
      parameters (group C) and molecular markers (tissue microarrays; group D) were
      collected from 512 early-stage nonsmall cell lung cancer (NSCLC) patients with
      complete resection. A multivariate analysis stepped supervised learning
      classification algorithm was used. The prognostic performance by groups was:
      areas under the receiver operating characteristic curve (C-index): 0.67 (group
      A), 0.65 (Group B), 0.57 (group C) and 0.65 (group D). Considering all variables
      together selected for each of the four groups (integrated group) the C-index was
      0.74 (95% CI 0.70-0.79), with statistically significant differences compared with
      each isolated group (from p = 0.006 to p < 0.001). Variables with the greatest
      prognostic discrimination were the presence of another ipsilobar nodule and
      tumour size > 3 cm, followed by other anatomical and clinical factors, and
      molecular expressions of phosphorylated mammalian target of rapamycin (phospho
      mTOR), Ki67cell proliferation index and phosphorylated acetyl-coenzyme A
      carboxylase. This study on early-stage NSCLC shows the benefit from integrating
      pathological TNM, clinical and molecular factors into a composite prognostic
      model. The model of the integrated group classified patients with significantly
      higher accuracy compared to the TNM 2010 staging.

PMID- 20817703
TI  - How deadly is seasonal influenza-associated pneumonia? The German Competence
      Network for Community-Acquired Pneumonia.
AB  - The emergence of new influenza virus subtypes has rekindled the interest in the
      clinical course and outcome of patients with influenza-associated pneumonia.
      Based on prospective data from 5,032 patients with community-acquired pneumonia
      (CAP) included in the German Competence Network for Community-Acquired Pneumonia
      (CAPNETZ), we studied the incidence, clinical characteristics and outcome of
      patients with influenza-associated CAP and compared these findings with patients
      without influenza. Diagnosis relied on a positive PCR for influenza in throat
      washings. 160 patients with influenza-associated CAP were identified (3.2% of
      total population, 12% of those with defined aetiology). 34 (21%) patients with
      seasonal influenza had a concomitant pathogen (mostly Streptococcus pneumoniae).
      Patients with influenza-associated CAP were significantly older, had been
      vaccinated less often and had preceding antibacterial treatment less often. 30
      day mortality was low (4.4%) and not different to that of patients with pneumonia
      caused by bacterial (6.2%) or viral (other than influenza) pathogens (4%).
      Patients with influenza plus a bacterial pathogen (mixed influenza-associated
      pneumonia) had a higher mortality than those with pure influenza-associated
      pneumonia (9% versus 3.2%). Mortality was higher in patients with mixed compared
      with pure influenza-associated pneumonia. However, we could not observe any
      excess mortality in patients with influenza-associated pneumonia.

PMID- 20817704
TI  - The cost of medical management of pulmonary nontuberculous mycobacterial disease
      in Ontario, Canada.
AB  - Treatment of pulmonary nontuberculous mycobacterial (NTM) infection is complex,
      requiring multiple antibiotics and a prolonged treatment course. We determined
      the monthly cost of treating patients with pulmonary NTM infections in our
      clinic, a tertiary care centre in Toronto, Ontario, Canada. We reviewed records
      of a single clinic at the University Health Network (Toronto) for all patients
      with pulmonary NTM isolates. Pharmacological and nonpharmacological treatment
      costs were calculated using a number of Canadian references. 172 patients were
      reviewed, 91 of whom were treated pharmacologically. The median total duration
      and cost per treated patient were 14 months (interquartile range (IQR) 9-23
      months) and CAD 4,916 (IQR CAD 2,934-9,063), respectively. Median monthly drug
      treatment cost was CAD 321 (IQR CAD 254-458) for all patients, CAD 289 (IQR CAD
      237-341) for patients receiving exclusively oral antibiotics and CAD 1,161 (IQR
      CAD 795-1,646) for patients whose treatment included i.v. antibiotics. The most
      costly oral regiment consisted of a fluroquinolone, macrolide and rifampin. In
      multivariable analysis, Mycobacterium abscessus infection, i.v. therapy and
      Mycobacterium xenopi infection were all associated with increased monthly
      treatment costs. The direct medical costs of NTM infections are substantial. Less
      expensive alternative therapies might be most helpful for M. abscessus infection
      and when i.v. antibiotics are deemed necessary.

PMID- 20817705
TI  - SerpinB1 in cystic fibrosis airway fluids: quantity, molecular form and mechanism
      of elastase inhibition.
AB  - Neutrophil serine proteases (NSPs), especially elastase, are major agents of lung
      destruction in cystic fibrosis (CF) patients. This study investigated SerpinB1, a
      highly efficient inhibitor of NSPs, in CF lung disease. Bronchoalveolar lavage
      fluid (BALF) from 31 children with CF and 24 control children was examined for
      amount and molecular species of SerpinB1, and its mechanism of action was
      studied. CF BALF had more SerpinB1 than control BALF (geometric mean 3.9 (95% CI
      2.60-5.62) versus 1.37 (1.20-1.55) MUg.mL-1; p<0.001). BALF levels of SerpinB1
      were higher for infected versus uninfected CF subjects (5.5 versus 2.7 MUg.mL-1;
      p<0.04) and substantially higher for elastase-positive versus -negative CF
      subjects (8.41 versus 1.89 MUg.mL-1; p<0.001). Most SerpinB1 in CF BALF had been
      cleaved. Adding recombinant SerpinB1 to CF BALF stoichiometrically inhibited
      endogenous elastase, indicating that the inhibitor functions in the CF
      microenvironment. In vitro simulations comparing SerpinB1 and alpha1-antitrypsin
      (SerpinA1) showed that both rapidly form irreversible inhibitory covalent
      complexes with elastase and that these differed in survival time. The SerpinB1
      elastase complex survived only briefly due to fragmentation of bound elastase,
      releasing cleaved SerpinB1, the molecular form in CF BALF. The findings define an
      innate role for SerpinB1 in CF airways.

PMID- 20817706
TI  - Respiratory health in children, and indoor exposure to (1,3)-beta-D-glucan, EPS
      mould components and endotoxin.
AB  - For a long time, exposure to mould and dampness-derived microbial components was
      considered a risk factor for the development of respiratory diseases and
      symptoms. Some recent studies suggested that early childhood exposure to mould
      components, such as (1,3)-beta-D-glucan and extracellular polysaccharides (EPSs),
      may protect children from developing allergy. We investigated the association of
      exposure to (1,3)-beta-D-glucan, EPS and endotoxin with asthma and allergies in 6
      yr-old children. This investigation was the follow-up to a nested case-control
      study among three European birth cohorts. Children from two ongoing birth cohort
      studies performed in Germany (n = 358) and one in the Netherlands (n = 338) were
      selected. Levels of (1,3)-beta-D-glucan, EPS and endotoxin were measured in
      settled house dust sampled from children's mattresses and living-room floors when
      the children were, on average, 5 yrs of age. At the age of 6 yrs, health outcome
      information was available for 678 children. In the two German subsets, domestic
      EPS and endotoxin exposure from children's mattresses were significantly
      negatively associated with physician-diagnosed asthma (OR per interquartile range
      increase 0.60 (95% CI 0.39-0.92) and 0.55 (95% CI 0.31-0.97), respectively). In
      addition, EPS exposure was inversely related to physician-diagnosed allergic
      rhinitis (OR 0.50, 95% CI 0.31-0.81). For the Dutch population, no associations
      were observed between exposure to microbial agents and respiratory health
      outcomes. We found inverse associations between domestic exposure to EPS and
      endotoxin from children's mattresses, and doctor-diagnosed asthma and rhinitis in
      German, but not in Dutch, school children. The reasons for the differences
      between countries are not clear.

PMID- 20817707
TI  - Influence of secular trends and sample size on reference equations for lung
      function tests.
AB  - The aim of our study was to determine the contribution of secular trends and
      sample size to lung function reference equations, and establish the number of
      local subjects required to validate published reference values. 30 spirometry
      datasets collected between 1978 and 2009 provided data on healthy, white
      subjects: 19,291 males and 23,741 females aged 2.5-95 yrs. The best fit for
      forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and
      FEV(1)/FVC as functions of age, height and sex were derived from the entire
      dataset using GAMLSS. Mean z-scores were calculated for individual datasets to
      determine inter-centre differences. This was repeated by subdividing one large
      dataset (3,683 males and 4,759 females) into 36 smaller subsets (comprising 18
      227 individuals) to preclude differences due to population/technique. No secular
      trends were observed and differences between datasets comprising >1,000 subjects
      were small (maximum difference in FEV(1) and FVC from overall mean: 0.30- -0.22 z
      scores). Subdividing one large dataset into smaller subsets reproduced the above
      sample size-related differences and revealed that at least 150 males and 150
      females would be necessary to validate reference values to avoid spurious
      differences due to sampling error. Use of local controls to validate reference
      equations will rarely be practical due to the numbers required. Reference
      equations derived from large or collated datasets are recommended.

PMID- 20817708
TI  - Signalling pathway of isophorone diisocyanate-responsive interleukin-8 in airway
      smooth muscle cells.
AB  - This study is the first to analyse the soluble factors secreted by the bronchial
      epithelium after exposure to isophorone diisocyanate (IPDI) that are responsible
      for increasing migration and proliferation of primary normal human bronchial
      smooth muscle cells (BSMCs). We treated immortalised, nontumorigenic human
      bronchial epithelial cells (cell line BEAS-2B) and primary normal human bronchial
      epithelial cells (HBEC) with IPDI, and then collected the conditioned culture
      media (IPDI-BEAS-2B-CM and IPDI-HBEC-CM, respectively), which was added to BSMCs.
      Exposure of BEAS-2B cells and HBECs to IPDI increased interleukin (IL)-8
      production. Culture of BSMCs with IPDI-BEAS-2B-CM and IPDI-HBEC-CM increased BSMC
      proliferation and migration, which are major features in asthma-related airway
      remodelling. Induction of BSMC proliferation and migration by IPDI-BEAS-2B-CM and
      IPDI-HBEC-CM was associated with increased focal adhesion kinase (FAK), Src,
      extracellular signal-regulated kinase (ERK)1/2 and AKT activation. Blocking FAK
      with a specific inhibitor significantly decreased BSMC migration and
      proliferation by inhibiting ERK1/2 activation. FAK and ERK1/2 inhibitor also
      decreased IPDI-BEAS-2B-CM-, IPDI-HBEC-CM- and recombinant human IL-8-mediated
      BSMC proliferation and migration, whereas blocking Rnd3 using small interfering
      RNA failed to affect BSMC proliferation, suggesting that Rnd3 was only involved
      in the regulation of BSMC migration. Our study suggests that inhibition of IL-8
      or IL-8-mediated FAK/ERK/Rnd3 signalling is an attractive therapeutic target for
      IPDI-mediated asthma.

PMID- 20817709
TI  - Bronchial hyperresponsiveness to methacholine/AMP and the bronchodilator response
      in asthmatic children.
AB  - Bronchodilator response (BDR) is assessed to estimate the reversibility of
      airflow obstruction. Bronchial hyperresponsiveness (BHR) is a characteristic
      feature of asthma and is usually measured by means of bronchial challenges using
      direct or indirect stimuli. The aim of the present study was to compare BHR to
      methacholine (direct) and that to adenosine 5'-monophosphate (AMP) (indirect)
      with regard to their relationships to BDR in asthmatic children. Methacholine and
      AMP challenge tests were performed on 138 children with mild-to-moderate asthma,
      and the provocative concentration causing a 20% decline in forced expiratory
      volume in 1 s (FEV1) (PC20) was determined for each challenge. BDR was calculated
      as the change in FEV(1), expressed as a percentage of the initial value, after
      inhalation of 400 MUg salbutamol. Methacholine PC20 correlated significantly but
      weakly with BDR (r = -0.254; p = 0.003). However, there was a significant and
      strong correlation between AMP PC20 and BDR (r = -0.489; p = 0.000). For AMP
      PC20, the relationship was closer than for methacholine PC20 (p = 0.024 for
      comparison between correlation coefficients). The same figures were observed when
      BDR was expressed as a percentage of the predicted value. A stronger correlation
      of BDR with AMP PC20 than with methacholine PC20 suggests that BDR may be better
      reflected by BHR as assessed by AMP challenge than by methacholine challenge.

PMID- 20817710
TI  - Adenotonsillectomy improves slow-wave activity in children with obstructive sleep
      apnoea.
AB  - The aim of the present study was to estimate slow-wave activity (SWA), a marker
      of sleep homeostasis, in children with obstructive sleep apnoea (OSA) before and
      after adenotonsillectomy (AT) compared with untreated OSA children (comparison
      group). 14 children with OSA (mean +/- sd age 6.4 +/- 2.5 yrs; apnoea-hypopnoea
      index (AHI) 10.0 +/- 10.3 events.h-1) who underwent AT were consecutively
      recruited to the study. The comparison group comprised six retrospectively
      recruited children (age 5.4 +/- 2.2 yrs; AHI 9.4 +/- 7.6 events.h-1) with OSA
      that did not undergo treatment. Electroencephalogram (derivation C3/A2) was
      analysed using spectral and waveform analysis to determine SWA energy and slow
      wave slope. The same procedure was repeated 5.4 and 19 months later for the AT
      and comparison groups, respectively. AT improved respiration without a change in
      duration of sleep stages. Following AT, >50% elevation of SWA during the first
      two sleep cycles (p<0.01) and a more physiological decay of SWA across the night
      (p<0.0001) were noted. The slow-wave slope increased by >30% following AT
      (p<0.03). No significant changes were found in SWA in the comparison group. Sleep
      homeostasis is considerably impaired in pre-pubescent children with OSA. AT
      restores more physiological sleep homeostasis in children with OSA. SWA analysis
      may provide a useful addition to standard sleep-stage analyses in children with
      OSA.

PMID- 20817711
TI  - Sex differences in obstructive sleep apnoea in an elderly French population.
AB  - Obstructive sleep apnoea (OSA) affects females and males differently, and
      increases in prevalence with age. The aim of the present study was to
      characterise clinical, anthropometric and polygraphic sex differences in a large
      elderly OSA population. A total of 641 subjects aged 68 yrs were examined.
      Measurements of fat mass, using dual-energy X-ray absorptiometry (DEXA) and
      polygraphy, were obtained in all subjects. An apnoea/hypopnoea index (AHI) of >15
      events.h-1 identified the presence of OSA. OSA was diagnosed in 57% of the
      sample, 34% having a mild form and 23% having an AHI of >30 events.h-1. Females
      with OSA exhibited a lower AHI, less severe hypoxaemia and greater peripheral fat
      mass, and frequently reported anxiety and depression. Comparison of females with
      and without OSA did not reveal significant differences in clinical,
      anthropometric and DEXA data. After adjustment for body mass index, hypertension,
      diabetes, smoking, anxiety and depression, logistic regression analysis revealed
      that the presence of hypertension was significantly associated with OSA risk in
      females (OR 1.52, p = 0.04). In a general community healthy population, the
      prevalence of undiagnosed OSA in females increases with age, with a risk similar
      to that in males. In females, the clinical spectrum, anthropometric data and fat
      distribution appear to be more sex-related than OSA-dependent. The occurrence of
      OSA contributes to hypertensive risk in elderly females.

PMID- 20817712
TI  - Hypercytokinaemia accompanies HIV-tuberculosis immune reconstitution inflammatory
      syndrome.
AB  - Increased access to combination antiretroviral therapy in areas co-endemic for
      tuberculosis (TB) and HIV-1 infection is associated with an increased incidence
      of immune reconstitution inflammatory syndrome (TB-IRIS) whose cause is poorly
      understood. A case-control analysis of pro- and anti-inflammatory cytokines in TB
      IRIS patients sampled at clinical presentation, and similar control patients with
      HIV-TB prescribed combined antiretroviral therapy who did not develop TB-IRIS.
      Peripheral blood mononuclear cells were cultured in the presence or absence of
      heat-killed Mycobacterium tuberculosis for 6 and 24 h. Stimulation with M.
      tuberculosis increased the abundance of many cytokine transcripts with
      interleukin (IL)-1beta, IL-5, IL-6, IL-10, IL-13, IL-17A, interferon (IFN)-gamma,
      granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumour necrosis
      factor (TNF) being greater in stimulated TB-IRIS cultures. Analysis of the
      corresponding proteins in culture supernatants, revealed increased IL-1beta, IL
      2, IL-6, IL-8, IL-10, IL-12p40, IFN-gamma, GM-CSF and TNF in TB-IRIS cultures. In
      serum, higher concentrations of TNF, IL-6, and IFN-gamma were observed in TB-IRIS
      patients. Serum IL-6 and TNF decreased during prednisone therapy in TB-IRIS
      patients. These data suggest that cytokine release contributes to pathology in TB
      IRIS. IL-6 and TNF were consistently elevated and decreased in serum during
      corticosteroid therapy. Specific blockade of these cytokines may be rational
      approach to immunomodulation in TB-IRIS.

PMID- 20817713
TI  - The relationship between single-parent status and parenting capacities in mothers
      of youth with chronic health conditions: the mediating role of income.
AB  - OBJECTIVE: To retrospectively examine the relationship of single-parent status to
      parenting capacity variables in mothers of youth with a chronic health condition.
      METHODS: Parental overprotection, perceived vulnerability, and parenting stress
      were assessed in 383 mothers (308 married and 75 single parents) of youth with
      one of six chronic health conditions (i.e., type 1 diabetes, asthma, cancer,
      cystic fibrosis, hemophilia, or sickle cell disease). RESULTS: Single mothers
      evidenced higher levels of both perceived vulnerability and parenting stress, but
      not overprotection, than married parents. These differences disappeared in the
      presence of income as a predictor. CONCLUSIONS: Single parents appear to evidence
      differences in parenting capacity; however, low income appears to account in
      large part for the higher level of risk associated with single-parent status.

PMID- 20817714
TI  - An intuitive, informative, and most balanced representation of phylogenetic
      topologies.
AB  - The recent explosion in the availability of genetic sequence data has made large
      scale phylogenetic inference routine in many life sciences laboratories. The
      outcomes of such analyses are, typically, a variety of candidate phylogenetic
      relationships or tree topologies, even when the power of genome-scale data is
      exploited. Because much phylogenetic information must be buried in such topology
      distributions, it is important to reveal that information as effectively as
      possible; however, existing methods need to adopt complex structures to represent
      such information. Hence, researchers, in particular those not experts in
      evolutionary studies, sometimes hesitate to adopt these methods and much
      phylogenetic information could be overlooked and wasted. In this paper, we
      propose the centroid wheel tree representation, which is an informative
      representation of phylogenetic topology distributions, and which can be readily
      interpreted even by nonexperts. Furthermore, we mathematically prove this to be
      the most balanced representation of phylogenetic topologies and efficiently
      solvable in the framework of the traveling salesman problem, for which very
      sophisticated program packages are available. This theoretically and practically
      superior representation should aid biologists faced with abundant data. The
      centroid representation introduced here is fairly general, so it can be applied
      to other fields that are characterized by high-dimensional solution spaces and
      large quantities of noisy data. The software is implemented in Java and available
      via http://cwt.cb.k.u-tokyo.ac.jp/.

PMID- 20817715
TI  - Using geographic information systems to compare the density of stores selling
      tobacco and alcohol: youth making an argument for increased regulation of the
      tobacco permitting process in Worcester, Massachusetts, USA.
AB  - BACKGROUND: This study is based on a community participatory research (CBPR)
      partnership between a youth group and a local university to explore whether
      greater regulation of tobacco permits would reduce the density of tobacco outlets
      overall, and particularly in low-income, high minority neighbourhoods in
      Worcester, Massachusetts, USA. METHODS: Applying Geographic Information Systems
      and regression analyses to neighbourhood demographics and the location of stores
      selling tobacco and alcohol, the study predicts the density of tobacco outlets as
      compared to alcohol outlets at the neighborhood block group level and in relation
      to the location and demographic composition of public schools. RESULTS: This
      study found that there are more than double the number of stores that sell
      tobacco as compared to alcohol in the city of Worcester. For every alcohol vendor
      there was a 41% increase in the estimated number of tobacco vendors, independent
      of the effect of other variables. The likelihood of having a tobacco outlet
      located near a school was greater than having an alcohol outlet as the percentage
      of minority students in schools increases. CONCLUSIONS: Based on these findings,
      the authors conclude that to reduce the impact of tobacco on socially and
      economically disadvantaged communities, the issuing of tobacco permits requires
      more regulation and oversight and should take into consideration the density and
      actual location of other licensees in an area.

PMID- 20817716
TI  - Survey of the use of non-invasive positive pressure ventilation in U.K. and
      Australasian children with cystic fibrosis.

PMID- 20817717
TI  - Plasma levels of TIMP-1 are higher in 34-year-old individuals with severe alpha1
      antitrypsin deficiency.

PMID- 20817718
TI  - New insights into the evolution of metazoan cadherins.
AB  - Mining newly sequenced genomes of basal metazoan organisms reveals the
      evolutionary origin of modern protein families. Specific cell-cell adhesion and
      intracellular communication are key processes in multicellular animals, and
      members of the cadherin superfamily are essential players in these processes.
      Mammalian genomes contain over 100 genes belonging to this superfamily. By a
      combination of tBLASTn and profile hidden Markov model analyses, we made an
      exhaustive search for cadherins and compiled the cadherin repertoires in key
      organisms, including Branchiostoma floridae (amphioxus), the sea anemone
      Nematostella vectensis, and the placozoan Trichoplax adhaerens. Comparative
      analyses of multiple protein domains within known and novel cadherins enabled us
      to reconstruct the complex evolution in metazoa of this large superfamily. Five
      main cadherin branches are represented in the primitive metazoan Trichoplax:
      classical (CDH), flamingo (CELSR), dachsous (DCHS), FAT, and FAT-like. Classical
      cadherins, such as E-cadherin, arose from an Urmetazoan cadherin, which
      progressively lost N-terminal extracellular cadherin repeats, whereas its
      cytoplasmic domain, which binds the armadillo proteins p120ctn and beta-catenin,
      remained quite conserved from placozoa to man. The origin of protocadherins
      predates the Bilateria and is likely rooted in an ancestral FAT cadherin. Several
      but not all protostomians lost protocadherins. The emergence of chordates
      coincided with a great expansion of the protocadherin repertoire. The evolution
      of ancient metazoan cadherins points to their unique and crucial roles in
      multicellular animal life.

PMID- 20817719
TI  - GC3 of genes can be used as a proxy for isochore base composition: a reply to
      Elhaik et al.
AB  - In an article published in these pages, Elhaik et al. (Elhaik E, Landan G, Graur
      D. 2009. Can GC content at third-codon positions be used as a proxy for isochore
      composition? Mol Biol Evol. 26:1829-1833) asked if GC3, the GC level of the third
      codon positions in protein-coding genes, can be used as a "proxy" to estimate the
      GC level of the surrounding isochore. We use available data to directly answer
      this simple question in the affirmative and show how the use of indirect methods
      can lead to apparently conflicting conclusions. The answer reasserts that in
      human and other vertebrates, genes have a strong tendency to reside in
      compositionally corresponding isochores, which has far-reaching implications for
      genome structure and evolution.

PMID- 20817720
TI  - Functional shifts in insect microRNA evolution.
AB  - MicroRNAs (miRNAs) are short endogenous RNA molecules that regulate gene
      expression at the posttranscriptional level and have been shown to play critical
      roles during animal development. The identification and comparison of miRNAs in
      metazoan species are therefore paramount for our understanding of the evolution
      of body plans. We have characterized 203 miRNAs from the red flour beetle
      Tribolium castaneum by deep sequencing of small RNA libraries. We can conclude,
      from a single study, that the Tribolium miRNA set is at least 15% larger than
      that in the model insect Drosophila melanogaster (despite tens of high-throughput
      sequencing experiments in the latter). The rate of birth and death of miRNAs is
      high in insects. Only one-third of the Tribolium miRNA sequences are conserved in
      D. melanogaster, and at least 18 Tribolium miRNAs are conserved in vertebrates
      but lost in Drosophila. More than one-fifth of miRNAs that are conserved between
      Tribolium and Drosophila exhibit changes in the transcription, genomic
      organization, and processing patterns that lead to predicted functional shifts.
      For example, 13% of conserved miRNAs exhibit seed shifting, and we describe arm
      switching events in 11% of orthologous pairs. These shifts fundamentally change
      the predicted targets and therefore function of orthologous miRNAs. In general,
      Tribolium miRNAs are more representative of the insect ancestor than Drosophila
      miRNAs and are more conserved in vertebrates.

PMID- 20817721
TI  - An impaired renal function and advanced heart failure represent independent
      predictors of the incidence of malignant ventricular arrhythmias in patients with
      an implantable cardioverter/defibrillator for primary prevention.
AB  - AIMS: Malignant ventricular arrhythmias and inappropriate therapies represent
      unsolved problems in patients with implantable cardioverter/defibrillator (ICD)
      for primary prevention. This study focuses on the incidence of such therapies and
      thereby seeks to identify new predictors of adverse events to enhance risk
      stratification. METHODS AND RESULTS: Ninety-four consecutive patients with mild
      to-moderate heart failure (NYHA II-III) and depressed left ventricular function
      (<=35%) were followed for 34 +/- 20 months. Two hundred and ninety-one malignant
      ventricular arrhythmias were documented in 51 patients (54%). Eighteen patients
      (19%) received inappropriate ICD therapies (e.g. atrial fibrillation, sinus
      tachycardia, etc.). Patients with malignant arrhythmia (1.34 +/- 0.44 vs. 1.16 +/
      0.4 mg/dL, P = 0.017) and patients suffering from inappropriate ICD therapies
      (1.54 +/- 0.48 vs. 1.2 +/- 0.38 mg/dL; P = 0.007) revealed a significantly worse
      renal function before ICD implantation than participants without any therapy. An
      increased serum creatinine at baseline (2 vs. 1 mg/dL; odds ratio (OR) 3.96; P =
      0.02; 95% CI: 1.2-13.04) and NHYA class III compared with II (OR: 2.96; P = 0.02;
      95% CI: 1.16-7.48) represent strong and independent predictors for the occurrence
      of ventricular arrhythmias. Moreover, an impaired renal function is identified as
      an independent risk factor for inappropriate therapies (OR: 5.6; P = 0.004; 95%
      CI: 1.72-18.22). CONCLUSION: An impaired renal function and advanced heart
      failure before ICD implantation for primary prevention are identified as
      independent predictors for the incidence of appropriate ICD interventions. With
      regard to current guidelines and economical aspects, patients suffering from an
      impaired renal function or advanced heart failure seem to benefit most from ICD
      therapy.

PMID- 20817722
TI  - Characterization of the core mammalian clock component, NPAS2, as a REV
      ERBalpha/RORalpha target gene.
AB  - The mammalian clock is regulated at the cellular level by a
      transcriptional/translational feedback loop. BMAL1/clock (or NPAS2) heterodimers
      activate the expression of the period (PER) and cryptochrome (CRY) genes acting
      as transcription factors directed to the PER and CRY promoters via E-box
      elements. PER and CRY proteins form heterodimers and suppress the activity of the
      BMAL1/clock (or NPAS2) completing the feedback loop. The circadian expression of
      BMAL1 is influenced by retinoic acid receptor-related orphan receptor alpha
      (RORalpha) and REV-ERBalpha, two nuclear receptors that target a ROR-response
      element in the promoter of the BMAL1 gene. Given that BMAL1 functions as an
      obligate heterodimer with either clock or NPAS2, it is unclear how the expression
      of the partner is coordinated with BMAL1 expression. Here, we demonstrate that
      NPAS2 is also a RORalpha and REV-ERBalpha target gene. Using a ChIP/microarray
      screen, we identified both RORalpha and REV-ERBalpha occupancy of the NPAS2
      promoter. We identified two functional ROREs within the NPAS2 promoter and also
      demonstrate that both RORalpha and REV-ERBalpha regulate the expression of NPAS2
      mRNA. These data suggest a mechanism by which RORalpha and REV-ERBalpha
      coordinately regulate the expression of the positive arm of the circadian rhythm
      feedback loop.

PMID- 20817723
TI  - Intracellular activation of interferon regulatory factor-1 by nanobodies to the
      multifunctional (Mf1) domain.
AB  - IRF-1 is a tumor suppressor protein that activates gene expression from a range
      of promoters in response to stimuli spanning viral infection to DNA damage.
      Studies on the post-translational regulation of IRF-1 have been hampered by a
      lack of suitable biochemical tools capable of targeting the endogenous protein.
      In this study, phage display technology was used to develop a monoclonal nanobody
      targeting the C-terminal Mf1 domain (residues 301-325) of IRF-1. Intracellular
      expression of the nanobody demonstrated that the transcriptional activity of IRF
      1 is constrained by the Mf1 domain as nanobody binding gave an increase in
      expression from IRF-1-responsive promoters of up to 8-fold. Furthermore, Mf1
      directed nanobodies have revealed an unexpected function for this domain in
      limiting the rate at which the IRF-1 protein is degraded. Thus, the increase in
      IRF-1 transcriptional activity observed on nanobody binding is accompanied by a
      significant reduction in the half-life of the protein. In support of the data
      obtained using nanobodies, a single point mutation (P325A) involving the C
      terminal residue of IRF-1 has been identified, which results in greater
      transcriptional activity and a significant increase in the rate of degradation.
      The results presented here support a role for the Mf1 domain in limiting both IRF
      1-dependent transcription and the rate of IRF-1 turnover. In addition, the data
      highlight a route for activation of downstream genes in the IRF-1 tumor
      suppressor pathway using biologics.

PMID- 20817724
TI  - Secretion stimulates intramembrane proteolysis of a secretory granule membrane
      enzyme.
AB  - Regulated intramembrane proteolysis, a highly conserved process employed by
      diverse regulatory pathways, can release soluble fragments that directly or
      indirectly modulate gene expression. In this study we used pharmacological tools
      to identify peptidylglycine alpha-amidating monooxygenase (PAM), a type I
      secretory granule membrane protein, as a gamma-secretase substrate. PAM, an
      essential enzyme, catalyzes the final step in the synthesis of the majority of
      neuropeptides that control metabolic homeostasis. Mass spectroscopy was most
      consistent with the presence of multiple closely spaced NH(2) termini, suggesting
      that cleavage occurred near the middle of the PAM transmembrane domain. The
      luminal domains of PAM must undergo a series of prohormone convertase or alpha
      secretase-mediated cleavages before the remaining transmembrane domain/cytosolic
      domain fragment can undergo a gamma-secretase-like cleavage. Cleavage by gamma
      secretase generates a soluble fragment of the cytosolic domain (sf-CD) that is
      known to localize to the nucleus. Although PAM sf-CD is unstable in AtT-20
      corticotroph tumor cells, it is readily detected in primary rat anterior
      pituitary cells. PAM isoform expression, which is tissue-specific and
      developmentally regulated, affects the efficiency with which sf-CD is produced.
      sf-CD levels are also modulated by the phosphorylation status of the cytosolic
      domain and by the ability of the cytosolic domain to interact with cytosolic
      proteins. sf-CD is produced by primary rat anterior pituitary cells in response
      to secretogogue, suggesting that sf-CD acts as a signaling molecule relaying
      information about secretion from the secretory granule to the nucleus.

PMID- 20817725
TI  - Members of the YjgF/YER057c/UK114 family of proteins inhibit phosphoribosylamine
      synthesis in vitro.
AB  - The YjgF/YER057c/UK114 family of proteins is highly conserved across all three
      domains of life and currently lacks a consensus biochemical function. Analysis of
      Salmonella enterica strains lacking yjgF has led to a working model in which YjgF
      functions to remove potentially toxic secondary products of cellular enzymes.
      Strains lacking yjgF synthesize the thiamine precursor phosphoribosylamine (PRA)
      by a TrpD-dependent mechanism that is not present in wild-type strains. Here, PRA
      synthesis was reconstituted in vitro with anthranilate phosphoribosyltransferase
      (TrpD), threonine dehydratase (IlvA), threonine, and phosphoribosyl
      pyrophosphate. TrpD-dependent PRA formation in vitro was inhibited by S. enterica
      YjgF and the human homolog UK114. Thus, the work herein describes the first
      biochemical assay for diverse members of the highly conserved YjgF/YER057c/UK114
      family of proteins and provides a means to dissect the cellular functions of
      these proteins.

PMID- 20817726
TI  - Excessive Na+/H+ exchange in disruption of dendritic Na+ and Ca2+ homeostasis and
      mitochondrial dysfunction following in vitro ischemia.
AB  - Neuronal dendrites are vulnerable to injury under diverse pathological
      conditions. However, the underlying mechanisms for dendritic Na(+) overload and
      the selective dendritic injury remain poorly understood. Our current study
      demonstrates that activation of NHE-1 (Na(+)/H(+) exchanger isoform 1) in
      dendrites presents a major pathway for Na(+) overload. Neuronal dendrites
      exhibited higher pH(i) regulation rates than soma as a result of a larger surface
      area/volume ratio. Following a 2-h oxygen glucose deprivation and a 1-h
      reoxygenation, NHE-1 activity was increased by ~70-200% in dendrites. This
      elevation depended on activation of p90 ribosomal S6 kinase. Moreover,
      stimulation of NHE-1 caused dendritic Na(+)(i) accumulation, swelling, and a
      concurrent loss of Ca(2+)(i) homeostasis. The Ca(2+)(i) overload in dendrites
      preceded the changes in soma. Inhibition of NHE-1 or the reverse mode of
      Na(+)/Ca(2+) exchange prevented these changes. Mitochondrial membrane potential
      in dendrites depolarized 40 min earlier than soma following oxygen glucose
      deprivation/reoxygenation. Blocking NHE-1 activity not only attenuated loss of
      dendritic mitochondrial membrane potential and mitochondrial Ca(2+) homeostasis
      but also preserved dendritic membrane integrity. Taken together, our study
      demonstrates that NHE-1-mediated Na(+) entry and subsequent Na(+)/Ca(2+) exchange
      activation contribute to the selective dendritic vulnerability to in vitro
      ischemia.

PMID- 20817727
TI  - Sequence-dependent prion protein misfolding and neurotoxicity.
AB  - Prion diseases are neurodegenerative disorders caused by misfolding of the normal
      prion protein (PrP) into a pathogenic "scrapie" conformation. To better
      understand the cellular and molecular mechanisms that govern the conformational
      changes (conversion) of PrP, we compared the dynamics of PrP from mammals
      susceptible (hamster and mouse) and resistant (rabbit) to prion diseases in
      transgenic flies. We recently showed that hamster PrP induces spongiform
      degeneration and accumulates into highly aggregated, scrapie-like conformers in
      transgenic flies. We show now that rabbit PrP does not induce spongiform
      degeneration and does not convert into scrapie-like conformers. Surprisingly,
      mouse PrP induces weak neurodegeneration and accumulates small amounts of scrapie
      like conformers. Thus, the expression of three highly conserved mammalian prion
      proteins in transgenic flies uncovered prominent differences in their
      conformational dynamics. How these properties are encoded in the amino acid
      sequence remains to be elucidated.

PMID- 20817728
TI  - Allosteric inhibition of the epithelial Na+ channel through peptide binding at
      peripheral finger and thumb domains.
AB  - The epithelial Na(+) channel (ENaC) mediates the rate-limiting step in
      transepithelial Na(+) transport in the distal segments of the nephron and in the
      lung. ENaC subunits are cleaved by proteases, resulting in channel activation due
      to the release of inhibitory tracts. Peptides derived from these tracts inhibit
      channel activity. The mechanism by which these intrinsic inhibitory tracts reduce
      channel activity is unknown, as are the sites where these tracts interact with
      other residues within the channel. We performed site-directed mutagenesis in
      large portions of the predicted periphery of the extracellular region of the
      alpha subunit and measured the effect of mutations on an 8-residue inhibitory
      tract-derived peptide. Our data show that the inhibitory peptide likely binds to
      specific residues within the finger and thumb domains of ENaC. Pairwise
      interactions between the peptide and the channel were identified by double mutant
      cycle experiments. Our data suggest that the inhibitory peptide has a specific
      peptide orientation within its binding site. Extended to the intrinsic inhibitory
      tract, our data suggest that proteases activate ENaC by removing residues that
      bind at the finger-thumb domain interface.

PMID- 20817729
TI  - SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid
      metabolism.
AB  - The SIRT1 deacetylase inhibits fat synthesis and stimulates fat oxidation in
      response to fasting, but the underlying mechanisms remain unclear. Here we report
      that SREBP-1c, a key lipogenic activator, is an in vivo target of SIRT1. SIRT1
      interaction with SREBP-1c was increased during fasting and decreased upon
      feeding, and consistently, SREBP-1c acetylation levels were decreased during
      fasting in mouse liver. Acetylated SREBP-1c levels were also increased in HepG2
      cells treated with insulin and glucose to mimic feeding conditions, and down
      regulation of p300 by siRNA decreased the acetylation. Depletion of hepatic SIRT1
      by adenoviral siRNA increased acetylation of SREBP-1c with increased lipogenic
      gene expression. Tandem mass spectrometry and mutagenesis studies revealed that
      SREBP-1c is acetylated by p300 at Lys-289 and Lys-309. Mechanistic studies using
      acetylation-defective mutants showed that SIRT1 deacetylates and inhibits SREBP
      1c transactivation by decreasing its stability and its occupancy at the lipogenic
      genes. Remarkably, SREBP-1c acetylation levels were elevated in diet-induced
      obese mice, and hepatic overexpression of SIRT1 or treatment with resveratrol, a
      SIRT1 activator, daily for 1 week decreased acetylated SREBP-1c levels with
      beneficial functional outcomes. These results demonstrate an intriguing
      connection between elevated SREBP-1c acetylation and increased lipogenic gene
      expression, suggesting that abnormally elevated SREBP-1c acetylation increases
      SREBP-1c lipogenic activity in obese mice. Reducing acetylation of SREBP-1c by
      targeting SIRT1 may be useful for treating metabolic disorders, including fatty
      liver, obesity, and type II diabetes.

PMID- 20817730
TI  - Cooperative role of NF-{kappa}B and poly(ADP-ribose) polymerase 1 (PARP-1) in the
      TNF-induced inhibition of PHEX expression in osteoblasts.
AB  - Reduced bone mass is a common complication in chronic inflammatory diseases,
      although the mechanisms are not completely understood. The PHEX gene encodes a
      zinc endopeptidase expressed in osteoblasts and contributes to bone
      mineralization. The aim of this study was to determine the molecular mechanism
      involved in TNF-mediated down-regulation of Phex gene transcription. We
      demonstrate down-regulation of the Phex gene in two models of colitis: naive T
      cell transfer and in gnotobiotic IL-10(-/-) mice. In vitro, TNF decreased
      expression of Phex in UMR106 cells and did not require de novo synthesis of a
      transrepressor. Transfecting UMR-106 cells with a series of deletion constructs
      of the proximal Phex promoter identified a region located within -74 nucleotides
      containing NF-kappaB and AP-1 binding sites. After TNF treatment, the RelA/p50 NF
      kappaB complex interacted with two cis-elements at positions -70/-66 and -29/-25
      nucleotides in the proximal Phex promoter. Inhibition of NF-kappaB signaling
      increased the basal level of Phex transcription and abrogated the effects of TNF,
      whereas overexpression of RelA mimicked the effect of TNF. We identified poly(ADP
      ribose) polymerase 1 (PARP-1) binding immediately upstream of the NF-kappaB sites
      and showed that TNF induced poly(ADP-ribosyl)ation of RelA when bound to the Phex
      promoter. TNF-mediated Phex down-regulation was completely abrogated in vitro by
      PARP-1 inhibitor and overexpression of poly(ADP-ribose) glucohydrolase (PARG) and
      in vivo in PARP-1(-/-) mice. Our results suggest that NF-kappaB signaling and
      PARP-1 enzymatic activity cooperatively contribute to the constitutive and
      inducible suppression of Phex. The described phenomenon likely contributes to the
      loss of bone mass density in chronic inflammatory diseases, such as inflammatory
      bowel disease.

PMID- 20817731
TI  - Sorting motifs of the endosomal/lysosomal CLC chloride transporters.
AB  - The CLC protein family contains plasma membrane chloride channels and the
      intracellular chloride-proton exchangers ClC-3-7. The latter proteins mainly
      reside on the various compartments of the endosomal-lysosomal system where they
      are involved in the luminal acidification or chloride accumulation. Although
      their partially overlapping subcellular distribution has been studied
      extensively, little is known about their targeting mechanism. In a comprehensive
      study we now performed pulldown experiments to systematically map the
      differential binding of adaptor proteins of the endosomal sorting machinery
      (adaptor proteins and GGAs (Golgi-localized, gamma-ear containing, Arf binding))
      as well as clathrin to the cytosolic regions of the intracellular CLCs. The
      resulting interaction pattern fitted well to the known subcellular localizations
      of the CLCs. By mutating potential sorting motifs, we could locate almost all
      binding sites, including one already known for ClC-3 and several new motifs for
      ClC-5, -6, and -7. The impact of the identified binding sites on the subcellular
      localization of CLC transporters was determined by heterologous expression of
      mutants. Surprisingly, some vesicular CLCs retained their localization after
      disruption of interaction sites. However, ClC-7 could be partially shifted from
      lysosomes to the plasma membrane by combined mutation of N-terminal sorting
      motifs. The localization of its beta-subunit, Ostm1, was determined by that of
      ClC-7. Ostm1 was not capable of redirecting ClC-7 to lysosomes.

PMID- 20817732
TI  - The exquisite structure and reaction mechanism of bacterial Pz-peptidase A toward
      collagenous peptides: X-ray crystallographic structure analysis of PZ-peptidase a
      reveals differences from mammalian thimet oligopeptidase.
AB  - Pz-peptidase A, from the thermophilic bacterium Geobacillus collagenovorans MO-1,
      hydrolyzes a synthetic peptide substrate, 4-phenylazobenzyloxycarbonyl-Pro-Leu
      Gly-Pro-D-Arg (Pz-PLGPR), which contains a collagen-specific tripeptide sequence,
      -Gly-Pro-X-, but does not act on collagen proteins themselves. The mammalian
      enzyme, thimet oligopeptidase (TOP), which has comparable functions with
      bacterial Pz-peptidases but limited identity at the primary sequence level, has
      recently been subjected to x-ray crystallographic analysis; however, no crystal
      structure has yet been reported for complexes of TOP with substrate analogues.
      Here, we report crystallization of recombinant Pz-peptidase A in complex with two
      phosphinic peptide inhibitors (PPIs) that also function as inhibitors of TOP and
      determination of the crystal structure of these complexes at 1.80-2.00 A
      resolution. The most striking difference between Pz-peptidase A and TOP is that
      there is no channel running the length of bacterial protein. Whereas the
      structure of TOP resembles an open bivalve, that of Pz-peptidase A is closed and
      globular. This suggests that collagenous peptide substrates enter the tunnel at
      the top gateway of the closed Pz-peptidase A molecule, and reactant peptides are
      released from the bottom gateway after cleavage at the active site located in the
      center of the tunnel. One of the two PPIs, PPI-2, which contains the collagen
      specific sequence, helped to clarify the exquisite structure and reaction
      mechanism of Pz-peptidase A toward collagenous peptides. This study describes the
      mode of substrate binding and its implication for the mammalian enzymes.

PMID- 20817733
TI  - Identification of a novel transport-independent function of PiT1/SLC20A1 in the
      regulation of TNF-induced apoptosis.
AB  - PiT1/SLC20A1 is a sodium-dependent P(i) transporter expressed by most mammalian
      cells. Interestingly, PiT1 transcription has been shown to be up-regulated by the
      tumor necrosis factor alpha (TNF), and we have now investigated the possible
      involvement of PiT1 in TNF-induced apoptosis. We show that PiT1-depleted cells
      are more sensitive to the proapoptotic activity of TNF (i.e. when the
      antiapoptotic NFkappaB pathway is inactivated). These observations were made in
      the human HeLa cancer cell line either transiently or stably depleted in PiT1 by
      RNA interference and in immortalized mouse embryonic fibroblasts isolated from
      PiT1 knock-out embryos. Depletion of the closely related family member PiT2 had
      no effect on TNF-induced apoptosis, showing that this effect was specific to
      PiT1. The increased sensitivity of PiT1-depleted cells was evident regardless of
      the presence or absence of extracellular P(i), suggesting that a defect in P(i)
      uptake was not involved in the observed phenotype. Importantly, we show that the
      re-expression of a P(i) uptake mutant of PiT1 in PiT1(-/-) mouse embryonic
      fibroblasts delays apoptosis as efficiently as the WT protein, showing that this
      function of PiT1 is unrelated to its transport activity. Caspase-8 is more
      activated in PiT1-depleted cells, and our data reveal that the sustained
      activation of the MAPK JNK is up-regulated in response to TNF. JNK activity is
      actually involved in PiT1-depleted cell death because specific JNK inhibitors
      delay apoptosis.

PMID- 20817734
TI  - Genetic ablation of calcium-independent phospholipase A2gamma prevents obesity
      and insulin resistance during high fat feeding by mitochondrial uncoupling and
      increased adipocyte fatty acid oxidation.
AB  - Phospholipases are critical enzyme mediators participating in many aspects of
      cellular function through modulating the generation of lipid 2nd messengers,
      membrane physical properties, and cellular bioenergetics. Here, we demonstrate
      that mice null for calcium-independent phospholipase A(2)gamma (iPLA(2)gamma(-/
      )) are completely resistant to high fat diet-induced weight gain, adipocyte
      hypertrophy, hyperinsulinemia, and insulin resistance, which occur in
      iPLA(2)gamma(+/+) mice after high fat feeding. Notably, iPLA(2)gamma(-/-) mice
      were lean, demonstrated abdominal lipodystrophy, and remained insulin-sensitive
      despite having a marked impairment in glucose-stimulated insulin secretion after
      high fat feeding. Respirometry of adipocyte explants from iPLA(2)gamma(-/-) mice
      identified increased rates of oxidation of multiple different substrates in
      comparison with adipocyte explants from wild-type littermates. Shotgun lipidomics
      of adipose tissue from wild-type mice demonstrated the anticipated 2-fold
      increase in triglyceride content after high fat feeding. In sharp contrast, the
      adipocyte triglyceride content was identical in iPLA(2)gamma(-/-) mice fed either
      a standard diet or a high fat diet. Respirometry of skeletal muscle mitochondria
      from iPLA(2)gamma(-/-) mice demonstrated marked decreases in state 3 respiration
      using multiple substrates whose metabolism was uncoupled from ATP production.
      Shotgun lipidomics of skeletal muscle revealed a decreased content of cardiolipin
      with an altered molecular species composition thereby identifying the mechanism
      underlying mitochondrial uncoupling in the iPLA(2)gamma(-/-) mouse. Collectively,
      these results identify iPLA(2)gamma as an obligatory upstream enzyme that is
      necessary for efficient electron transport chain coupling and energy production
      through its participation in the alterations of cellular bioenergetics that
      promote the development of the metabolic syndrome.

PMID- 20817735
TI  - Insights from selective non-phosphinic inhibitors of MMP-12 tailored to fit with
      an S1' loop canonical conformation.
AB  - After the disappointment of clinical trials with early broad spectrum synthetic
      inhibitors of matrix metalloproteinases (MMPs), the field is now resurging with a
      new focus on the development of selective inhibitors that fully discriminate
      between different members of the MMP family with several therapeutic applications
      in perspective. Here, we report a novel class of highly selective MMP-12
      inhibitors, without a phosphinic zinc-binding group, designed to plunge deeper
      into the S(1)' cavity of the enzyme. The best inhibitor from this series,
      identified through a systematic chemical exploration, displays nanomolar potency
      toward MMP-12 and selectivity factors that range between 2 and 4 orders of
      magnitude toward a large set of MMPs. Comparison of the high resolution x-ray
      structures of MMP-12 in free state or bound to this new MMP-12 selective
      inhibitor reveals that this compound fits deeply within the S(1)' specificity
      cavity, maximizing surface/volume ratios, without perturbing the S(1)' loop
      conformation. This is in contrast with highly selective MMP-13 inhibitors that
      were shown to select a particular S(1)' loop conformation. The search for such
      compounds that fit precisely to preponderant S(1)' loop conformation of a
      particular MMP may prove to be an alternative effective strategy for developing
      selective inhibitors of MMPs.

PMID- 20817736
TI  - Characterization of leukocyte mono-immunoglobulin-like receptor 7 (LMIR7)/CLM-3
      as an activating receptor: its similarities to and differences from LMIR4/CLM-5.
AB  - Here we characterize leukocyte mono-Ig-like receptor 7 (LMIR7)/CLM-3 and compare
      it with an activating receptor, LMIR4/CLM-5, that is a counterpart of an
      inhibitory receptor LMIR3/CLM-1. LMIR7 shares high homology with LMIR4 in the
      amino acid sequences of its Ig-like and transmembrane domains. Flow cytometric
      analysis demonstrated that LMIR4 was predominantly expressed in neutrophils,
      whereas LMIR7 was highly expressed in mast cells and monocytes/macrophages.
      Importantly, LMIR7 engagement induced cytokine production in bone marrow-derived
      mast cells (BMMCs). Although FcRgamma deficiency did not affect surface
      expression levels of LMIR7, it abolished LMIR7-mediated activation of BMMCs.
      Consistently we found significant interaction of LMIR7-FcRgamma, albeit with
      lower affinity compared with that of LMIR4-FcRgamma. Our results showed that
      LMIR7 transmits an activating signal through interaction with FcRgamma. In
      addition, like LMIR4, LMIR7 synergizes with TLR4 in signaling. Analysis of
      several chimera receptors composed of LMIR4 and LMIR7 revealed these findings: 1)
      the transmembrane of LMIR7 with no charged residues maintained its surface
      expression at high levels in the absence of FcRgamma; 2) the extracellular
      juxtamembrane region of LMIR7 had a negative effect on its surface expression
      levels; and 3) the strong interaction of LMIR4 with FcRgamma depended on the
      extracellular juxtamembrane region as well as the transmembrane domain of LMIR4.
      Thus, LMIR7 shares similarities with LMIR4, although they are differentially
      regulated in their distribution, expression, and function.

PMID- 20817737
TI  - Full repression of RNA polymerase III transcription requires interaction between
      two domains of its negative regulator Maf1.
AB  - Maf1, first identified in yeast Saccharomyces cerevisiae, is a general negative
      regulator of RNA polymerase III (Pol III). Transcription regulation by Maf1 is
      important under stress conditions and during the switch between fermentation and
      respiration. Maf1 is composed of two domains conserved during evolution. We
      report here that these two domains of human Maf1 are resistant to mild
      proteolysis and interact together as shown by pull-down and size-exclusion
      chromatography and that the comparable domains of yeast Maf1 interact in a two
      hybrid assay. Additionally, in yeast, a mutation in the N-terminal domain is
      compensated by mutations in the C-terminal domain. Integrity of both domains and
      their direct interaction are necessary for Maf1 dephosphorylation and subsequent
      inhibition of Pol III transcription on a nonfermentable carbon source. These data
      relate Pol III transcription inhibition to Maf1 structural changes.

PMID- 20817738
TI  - The "wh" questions of visual phonics: what, who, where, when, and why.
AB  - Visual Phonics is a reading instructional tool that has been implemented in
      isolated classrooms for over 20 years. In the past 5 years, several experimental
      studies demonstrated its efficacy with students who are deaf or hard of hearing.
      Through a national survey with 200 participants, this study specifically
      addresses who, where, how, and why a sample of teachers use Visual Phonics in
      their everyday reading instruction. Through checklists of teaching practice,
      rating scales, and open-ended questions, teachers self-reported their use of
      Visual Phonics, reflected upon its efficacy, and what they think about using it
      with students with a diverse set of instructional needs. The majority reported
      that Visual Phonics was easy to use, engaging to students, and easy to integrate
      into a structured reading curriculum. The majority of respondents agreed that it
      helps increase phonemic awareness and decoding skills, build vocabulary, as well
      as increase reading comprehension. The implications of these findings in bridging
      the research-to-practice gap are discussed.

PMID- 20817740
TI  - A qualitative study of New Zealand fertility counsellors' roles and practices
      regarding embryo donation.
AB  - BACKGROUND: Embryo donation is a recently approved practice in New Zealand.
      Guidelines require disclosure of donor identity, openness, joint donor and
      recipient counselling and ethics approval on a case-by-case basis. This study
      explores the roles and practices of fertility counsellors in the context of New
      Zealand's policies. METHODS: Nine fertility counsellors were interviewed
      regarding their roles in the practice of embryo donation. Data were thematically
      analysed to identify counsellors' key roles and concerns. RESULTS: Counsellors
      supported the principles underlying the policy in New Zealand. They saw their
      role as, firstly, helping patients shift from a focus on their current situations
      to considering the longer term psychosocial implications of embryo donation.
      Secondly, counsellors facilitated donors' and recipients' exploration of the
      implications not only for themselves but also for existing and potential children
      resulting from the donation and the effects on the wider family network.
      CONCLUSIONS: As determined by policy, counsellors play an integral role in
      facilitating embryo donation and regard their role as contributing to the long
      term wellbeing of families created through and affected by embryo donation.

PMID- 20817739
TI  - In utero exposure to tobacco smoke and subsequent reduced fertility in females.
AB  - BACKGROUND: Animal studies have shown that in utero exposure to chemicals in
      tobacco smoke reduces female fertility, but epidemiological findings have been
      inconsistent. METHODS: We examined the association between in utero exposure to
      tobacco smoke and female fertility among women in the Norwegian Mother and Child
      Cohort Study, enrolled from 1999 to 2007. Around the 17th week of pregnancy,
      participants reported how long they took to conceive (time to pregnancy), and
      whether their mother smoked while pregnant with the participant. This analysis
      included 48 319 planned pregnancies among women aged 15-44 years. We estimated
      fecundability odds ratios (FORs) using a discrete-time survival analysis,
      adjusting for age, education and adult tobacco smoking. RESULTS: The adjusted FOR
      for in utero exposure to tobacco smoke among all subjects was 0.96 [95%
      confidence interval (CI): 0.93, 0.98], among subjects reporting no adult tobacco
      smoking or passive exposure it was 0.96 (95% CI: 0.93, 0.99) and among subjects
      reporting adult tobacco smoking or passive exposure it was 0.95 (95% CI: 0.91,
      0.99). We performed a probabilistic sensitivity analysis to estimate the effect
      of exposure and outcome misclassification on the results, and, as expected, the
      association became more pronounced after taking misclassification into account.
      CONCLUSIONS: This large cohort study supports a small-to-modest association
      between in utero exposure to tobacco smoke and reduced fertility.

PMID- 20817741
TI  - Impact of drug transporters on cellular resistance towards saquinavir and
      darunavir.
AB  - OBJECTIVES: Highly active antiretroviral therapy is complicated by drug-drug
      interactions and the development of viral resistance. Drug interactions involve
      transporters that may critically affect the pharmacokinetics of many
      antiretroviral drugs and contribute to the formation of functional sanctuary
      sites. We therefore investigated the effect of saquinavir and darunavir on drug
      transporter expression and functional consequences for cellular resistance
      towards these compounds. METHODS: Induction of transporters was investigated in
      LS180 cells over a period of 4 weeks by means of RT-PCR, and for some
      transporters also at the protein and functional levels. Cellular resistance was
      measured by growth inhibition assays. RESULTS: Incubation with 10 uM darunavir
      for 1 week significantly increased mRNA expression of P-glycoprotein (P
      gp/MDR1/ABCB1) 3.8-fold and of organic anion-transporting polypeptide 2B1
      (SLCO2B1) 1.9-fold. In contrast, 10 uM saquinavir significantly increased mRNA
      expression of P-gp 5.7-fold, multidrug resistance-associated protein 1
      (MRP1/ABCC1) 2.3-fold, MRP2/ABCC2 4.5-fold, MRP3/ABCC3 2.0-fold, MRP4/ABCC4 1.8
      fold, MRP5/ABCC5 3.8-fold, breast cancer resistance protein (BCRP/ABCG2) 4.1
      fold, SLCO1B1 4.6-fold, SLCO2B1 1.8-fold and SLCO3A1 1.8-fold. P-gp induction was
      also confirmed at the protein and functional levels. Induction by darunavir
      caused an increase in cellular resistance towards this compound, as measured in
      growth inhibition assays; however, saquinavir treatment did not cause reduced
      sensitivity of cells, indicating unchanged intracellular concentration. Hence,
      induction by darunavir increased drug efflux and might therefore lead to a
      suboptimal intracellular concentration of darunavir. CONCLUSIONS: The study
      revealed substantial induction of several drug transporters by saquinavir and
      darunavir, possibly leading to decreased efficacy of antiretrovirals and drugs
      used to treat co-morbidity.

PMID- 20817742
TI  - Population pharmacokinetics of meropenem in burn patients.
AB  - OBJECTIVES: To develop a population pharmacokinetic model of meropenem in burn
      patients and to explore the appropriateness of current dosage regimens. PATIENTS
      AND METHODS: Fifty-nine patients with burns ranging from 3% to 97% of total body
      surface area treated with meropenem were analysed. The population pharmacokinetic
      parameters of meropenem in 59 burn patients were estimated, and concentrations
      were simulated by using a mixed effect method (NONMEM, ver. 6.2). RESULTS: The
      final model was a two-compartment model with first-order elimination where
      creatinine clearance (CL(CR)) and oedema contributed. The mean population
      pharmacokinetic parameters were clearance (L/h) =4.45 +10.5 * CL(CR)
      (mL/min)/138, V1 (central volume) =17.0+11.1 * presence of oedema (0 or 1) L, V2
      (peripheral volume) =10.1 L and Q (intercompartmental clearance) =5.25 L/h with
      interindividual variability (CV%) of 31.5%, 44.4%, 67.2% and 0% (not estimated),
      respectively. CONCLUSIONS: The population clearance and volume of distribution in
      our burn patients were significantly greater than those reported in non-burn
      patients. The simulation of 1000 virtual patients' plasma meropenem concentration
      treated with 1000 mg (30 min infusion) every 8 h based upon the model predicted
      the probability of achieving the time above MIC >40% of the dosing interval as
      58.9% for Pseudomonas aeruginosa isolated from three university hospitals in
      Korea.

PMID- 20817743
TI  - Using coalitional games on biological networks to measure centrality and power of
      genes.
AB  - MOTIVATION: The interpretation of gene interaction in biological networks
      generates the need for a meaningful ranking of network elements. Classical
      centrality analysis ranks network elements according to their importance but may
      fail to reflect the power of each gene in interaction with the others. RESULTS:
      We introduce a new approach using coalitional games to evaluate the centrality of
      genes in networks keeping into account genes' interactions. The Shapley value for
      coalitional games is used to express the power of each gene in interaction with
      the others and to stress the centrality of certain hub genes in the regulation of
      biological pathways of interest. The main improvement of this contribution, with
      respect to previous applications of game theory to gene expression analysis,
      consists in a finer resolution of the gene interaction investigated in the model,
      which is based on pairwise relationships of genes in the network. In addition,
      the new approach allows for the integration of a priori knowledge about genes
      playing a key function on a certain biological process. An approximation method
      for practical computation on large biological networks, together with a
      comparison with other centrality measures, is also presented.

PMID- 20817744
TI  - Using manifold embedding for assessing and predicting protein interactions from
      high-throughput experimental data.
AB  - MOTIVATION: High-throughput protein interaction data, with ever-increasing
      volume, are becoming the foundation of many biological discoveries, and thus high
      quality protein-protein interaction (PPI) maps are critical for a deeper
      understanding of cellular processes. However, the unreliability and paucity of
      current available PPI data are key obstacles to the subsequent quantitative
      studies. It is therefore highly desirable to develop an approach to deal with
      these issues from the computational perspective. Most previous works for
      assessing and predicting protein interactions either need supporting evidences
      from multiple information resources or are severely impacted by the sparseness of
      PPI networks. RESULTS: We developed a robust manifold embedding technique for
      assessing the reliability of interactions and predicting new interactions, which
      purely utilizes the topological information of PPI networks and can work on a
      sparse input protein interactome without requiring additional information types.
      After transforming a given PPI network into a low-dimensional metric space using
      manifold embedding based on isometric feature mapping (ISOMAP), the problem of
      assessing and predicting protein interactions is recasted into the form of
      measuring similarity between points of its metric space. Then a reliability
      index, a likelihood indicating the interaction of two proteins, is assigned to
      each protein pair in the PPI networks based on the similarity between the points
      in the embedded space. Validation of the proposed method is performed with
      extensive experiments on densely connected and sparse PPI network of yeast,
      respectively. Results demonstrate that the interactions ranked top by our method
      have high-functional homogeneity and localization coherence, especially our
      method is very efficient for large sparse PPI network with which the traditional
      algorithms fail. Therefore, the proposed algorithm is a much more promising
      method to detect both false positive and false negative interactions in PPI
      networks. AVAILABILITY: MATLAB code implementing the algorithm is available from
      the web site http://home.ustc.edu.cn/~yzh33108/Manifold.htm.

PMID- 20817746
TI  - The use of subcutaneous scopolamine as a palliative treatment in Parkinson's
      disease.
AB  - Parkinson's disease (PD) is a degenerative, chronic and irreversible condition.
      Palliative medicine may play an important role in the care of patients with PD to
      maintain the quality of life. Scopolamine is a non-competitive antagonist at
      muscarinic acetylcholine receptors, which was used many years ago in the
      treatment for PD. To the best of our knowledge, there are no previously reported
      cases of the use of scopolamine for symptom relief at the end of life in patients
      with PD. The case reported here shows that treatment with a subcutaneous
      scopolamine was a useful alternative in a terminal cancer patient with severe
      tremors unable to take oral PD medication.

PMID- 20817747
TI  - How to provide care for patients suffering from terminal non-oncological
      diseases: barriers to a palliative care approach.
AB  - Despite the seemingly evident pertinence of palliative care for patients
      suffering from non-oncological long-term life-threatening diseases, everyday
      clinical practice is far from that assumption. This study aims to explore
      palliative care service provision for these patients in Spain. Patients, family
      caregivers and healthcare professionals were interviewed, individually or in a
      group, aiming at identifying barriers in the provision of care and strategies to
      overcome them. Ritchie and Spencer's framework was used for data analysis. The
      barriers identified were as follows: lack of clarity about prognosis, the
      hegemony of the curative approach, avoiding words and the desire to cheat death.
      Provision of palliative care services for these patients should be guided by the
      characteristic trajectory of each type of disease. Even if healthcare systems
      were capable of providing specialized palliative care services to this large
      group of patients, other barriers should not be overlooked. It would then seem
      appropriate to provide therapeutic and palliative care simultaneously, thus
      facilitating adaptation processes for both patients and relatives.

PMID- 20817745
TI  - Genome-wide analysis of two-component systems and prediction of stress-responsive
      two-component system members in soybean.
AB  - In plants, the two-component systems (TCSs) play important roles in regulating
      diverse biological processes, including responses to environmental stress
      stimuli. Within the soybean genome, the TCSs consist of at least 21 histidine
      kinases, 13 authentic and pseudo-phosphotransfers and 18 type-A, 15 type-B, 3
      type-C and 11 pseudo-response regulator proteins. Structural and phylogenetic
      analyses of soybean TCS members with their Arabidopsis and rice counterparts
      revealed similar architecture of their TCSs. We identified a large number of
      closely homologous soybean TCS genes, which likely resulted from genome
      duplication. Additionally, we analysed tissue-specific expression profiles of
      those TCS genes, whose data are available from public resources. To predict the
      putative regulatory functions of soybean TCS members, with special emphasis on
      stress-responsive functions, we performed comparative analyses from all the TCS
      members of soybean, Arabidopsis and rice and coupled these data with annotations
      of known abiotic stress-responsive cis-elements in the promoter region of each
      soybean TCS gene. Our study provides insights into the architecture and a solid
      foundation for further functional characterization of soybean TCS elements. In
      addition, we provide a new resource for studying the conservation and divergence
      among the TCSs within plant species and/or between plants and other organisms.

PMID- 20817748
TI  - A comparison of palliative care outcome measures used to assess the quality of
      palliative care provided in long-term care facilities: a systematic review.
AB  - Provision of palliative care in long-term care (LTC) facilities is important, but
      limited research has been undertaken to investigate the most appropriate outcome
      measure for use in this setting. In this systematic review we aimed to measure
      the psychometric properties (reliability/validity) and feasibility of palliative
      outcome measures used to assess the quality of palliative care provided in LTC.
      For identification of outcome measures we undertook systematic searches of
      electronic databases from 1 January 2000 to 12 September 2008. Included studies
      were assessed by two independent reviewers for methodological quality prior to
      inclusion in the review using an appraisal checklist developed for the review to
      evaluate validity, reliability and feasibility. Ten articles were included in the
      final review and these provided specific information on the psychometric
      properties of 10 outcome measures. Four of these measures reported data
      specifically for residents in LTC facilities, while the remaining six measures
      reported a sub-set of data for residents in LTC facilities. The Family
      Perceptions of Care Scale is considered by the authors as the most suitable
      outcome measure for use in LTC facilities. Of the remaining nine measures, a
      further two were also considered suitable for measuring the quality of palliative
      care in residential aged care facilities. These are the Quality of Dying in Long
      term Care scale and the Toolkit Interview.

PMID- 20817749
TI  - Acute psychomotor, memory and subjective effects of MDMA and THC co
      administration over time in healthy volunteers.
AB  - In Western societies a considerable percentage of young people expose themselves
      to the combination of 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') and
      cannabis. The aim of the present study was to assess the acute effects of co
      administration of MDMA and THC (the main psychoactive compound of cannabis) on
      pharmacokinetics, psychomotor performance, memory and subjective experience over
      time. We performed a four-way, double blind, randomized, crossover, placebo
      controlled study in 16 healthy volunteers (12 male, four female) between the ages
      of 18 and 27. MDMA (100 mg) was given orally, THC (4, 6, and 6 mg, interval of 90
      min) was vaporized and inhaled. THC induced more robust cognitive impairment
      compared with MDMA, and co-administration did not exacerbate single drug effects
      on cognitive function. However, co-administration of THC with MDMA increased
      desired subjective drug effects and drug strength compared with the MDMA
      condition, which may explain the widespread use of this combination.

PMID- 20817750
TI  - Stress decreases the ability to resist smoking and potentiates smoking intensity
      and reward.
AB  - We have developed a novel human laboratory model to examine two primary aspects
      of stress-precipitated tobacco relapse: (1) Does stress reduce the ability to
      resist the first cigarette? (2) Once the first cigarette is initiated, does
      stress facilitate subsequent smoking? Using a within-subject design, daily
      smokers (n = 37) who were nicotine deprived overnight received a personalized
      imagery induction (stress or neutral) on two separate days, and then had the
      option of initiating a tobacco self-administration session or delaying initiation
      for up to 50 min in exchange for three levels of monetary reinforcement.
      Subsequently, the tobacco self-administration session entailed a 1-hour period in
      which subjects could choose to smoke using a smoking topography system. Following
      the stress induction, subjects were less able to resist smoking, smoked more
      intensely (increased puffs, shorter inter-puff interval, and greater peak puff
      velocity), and perceived greater satisfaction and reward from smoking. Stress
      significantly increased hypothalamus-pituitary-adrenal (HPA) axis reactivity,
      tobacco craving, negative emotion, and physiologic reactivity relative to the
      neutral condition. In addition, increased cortisol, ACTH, and tobacco craving
      were associated with reduced ability to resist smoking following stress. These
      findings have implications for understanding the impact of stress on smoking
      relapse and model development to assess smoking lapse behavior.

PMID- 20817751
TI  - Knocking down the transcript of protein kinase C-lambda modulates hypothalamic
      glutathione peroxidase, melanocortin receptor and neuropeptide Y gene expression
      in amphetamine-treated rats.
AB  - It has been reported that neuropeptide Y (NPY) contributes to the behavioral
      response of amphetamine (AMPH), a psychostimulant. The present study examined
      whether protein kinase C (PKC)-lambda signaling was involved in this action.
      Moreover, possible roles of glutathione peroxidase (GP) and melanocortin receptor
      4 (MC4R) were also examined. Rats were given AMPH daily for 4 days. Hypothalamic
      NPY, PKClambda, GP and MC4R were determined and compared. Pretreatment with alpha
      methyl-para-tyrosine could block AMPH-induced anorexia, revealing that endogenous
      catecholamine was involved in regulating AMPH anorexia. PKClambda, GP and MC4R
      were increased with maximal response on Day 2 during AMPH treatment, which were
      concomitant with the decreases in NPY. cAMP response element binding protein
      (CREB) DNA binding activity was increased during AMPH treatment, revealing the
      involvement of CREB-dependent gene transcription. An interruption of cerebral
      PKClambda transcript could partly block AMPH-induced anorexia and partly reverse
      NPY, MC4R and GP mRNA levels to normal. These results suggest that PKClambda
      participates in regulating AMPH-induced anorexia via a modulation of hypothalamic
      NPY gene expression and that increases of GP and MC4R may contribute to this
      modulation. Our results provided molecular evidence for the regulation of AMPH
      induced behavioral response.

PMID- 20817752
TI  - Microsatellite instability in Arabidopsis increases with plant development.
AB  - Plant development consists of the initial phase of intensive cell division
      followed by continuous genome endoreduplication, cell growth, and elongation. The
      maintenance of genome stability under these conditions is the main task performed
      by DNA repair and genome surveillance mechanisms. Our previous work showed that
      the rate of homologous recombination repair in older plants decreases. We
      hypothesized that this age-dependent decrease in the recombination rate is
      paralleled with other changes in DNA repair capacity. Here, we analyzed
      microsatellite stability using transgenic Arabidopsis (Arabidopsis thaliana)
      plants that carry the nonfunctional beta-glucuronidase gene disrupted by
      microsatellite repeats. We found that microsatellite instability increased
      dramatically with plant age. We analyzed the contribution of various mechanisms
      to microsatellite instability, including replication errors and mistakes of DNA
      repair mechanisms such as mismatch repair, excision repair, and strand break
      repair. Analysis of total DNA polymerase activity using partially purified
      protein extracts showed an age-dependent decrease in activity and an increase in
      fidelity. Analysis of the steady-state RNA level of DNA replicative polymerases
      alpha, delta, Pol I-like A, and Pol I-like B and the expression of mutS homolog 2
      (Msh2) and Msh6 showed an age-dependent decrease. An in vitro repair assay showed
      lower efficiency of nonhomologous end joining in older plants, paralleled by an
      increase in Ku70 gene expression. Thus, we assume that the more frequent
      involvement of nonhomologous end joining in strand break repair and the less
      efficient end-joining repair together with lower levels of mismatch repair
      activities may be the main contributors to the observed age-dependent increase in
      microsatellite instability.

PMID- 20817753
TI  - Morpholino oligonucleotides do not participate perfectly in standard Watson-Crick
      complexes with RNA.
AB  - RNase P from E. coli will cleave a RNA at a site designated in a complex with an
      external guide sequence (EGS). The location of the site is determined by the
      Watson-Crick complementary sequence that can be formed between the RNA and the
      EGS. Morpholino oligonucleotides (PMOs) that have the same base sequences as any
      particular EGS will not direct cleavage by RNase P of the target RNA at the
      expected site in three mRNAs. Instead, cleavage occurs at a secondary site that
      does not correspond exactly to the expected Watson-Crick sequence in the PMO.
      This cleavage in the mRNA for a drug resistance gene, CAT mRNA, is at least
      second order in the concentration of the PMOs, but the mechanism is not
      understood yet and might be more complicated than a simple second-order reaction.
      EGSs and PMOs inhibit the reactions of each other effectively in a competitive
      fashion. A basic peptide attached to the PMO (PPMO) is more effective because of
      its binding properties to the mRNA as a substrate. However, a PMO is just as
      efficient as a PPMO on a mRNA that is mutated so that the canonical W-C site has
      been altered. The altered mRNA is not recognizable by effective extensive W-C
      pairing to an EGS or PMO. The complex of a PMO on a mutated mRNA as a substrate
      shows that the dimensions of the modified oligonucleotide cannot be the same as a
      naked piece of single-stranded RNA.

PMID- 20817754
TI  - Intragenic transcription of a noncoding RNA modulates expression of ASP3 in
      budding yeast.
AB  - Inter- and intragenic noncoding transcription is widespread in eukaryotic
      genomes; however, the purpose of these types of transcription is still poorly
      understood. Here, we show that intragenic sense-oriented transcription within the
      budding yeast ASP3 coding region regulates a constitutively and immediately
      accessible promoter for the transcription of full-length ASP3. Expression of this
      short intragenic transcript is independent of GATA transcription factors, which
      are essential for the activation of full-length ASP3, and independent of RNA
      polymerase II (RNAPII). Furthermore, we found that an intragenic control element
      is required for the expression of this noncoding RNA (ncRNA). Continuous
      expression of the short ncRNA maintains a high level of trimethylation of histone
      H3 at lysine 4 (H3K4me3) at the ASP3 promoter and makes this region more
      accessible for RNAPII to transcribe the full-length ASP3. Our results show for
      the first time that intragenic noncoding transcription promotes gene expression.

PMID- 20817755
TI  - Specificity and kinetics of 23S rRNA modification enzymes RlmH and RluD.
AB  - Along the ribosome assembly pathway, various ribosomal RNA processing and
      modification reactions take place. Stem-loop 69 in the large subunit of
      Escherichia coli ribosomes plays a substantial role in ribosome functioning. It
      contains three highly conserved pseudouridines synthesized by pseudouridine
      synthase RluD. One of the pseudouridines is further methylated by RlmH. In this
      paper we show that RlmH has unique substrate specificity among rRNA modification
      enzymes. It preferentially methylates pseudouridine and less efficiently uridine.
      Furthermore, RlmH is the only known modification enzyme that is specific to 70S
      ribosomes. Kinetic parameters determined for RlmH are the following: The apparent
      K(M) for substrate 70S ribosomes is 0.51 +/- 0.06 MUM, and for cofactor S
      adenosyl-L-methionine 27 +/- 3 MUM; the k(cat) values are 4.95 +/- 1.10 min-1 and
      6.4 +/- 1.3 min-1, respectively. Knowledge of the substrate specificity and the
      kinetic parameters of RlmH made it possible to determine the kinetic parameters
      for RluD as well. The K(M) value for substrate 50S subunits is 0.98 +/- 0.18 MUM
      and the k(cat) value is 1.97 +/- 0.46 min-1. RluD is the first rRNA pseudouridine
      synthase to be kinetically characterized. The determined rates of RluD- and RlmH
      directed modifications of 23S rRNA are compatible with the rate of 50S assembly
      in vivo. The fact that RlmH requires 30S subunits demonstrates the dependence of
      50S subunit maturation on the simultaneous presence of 30S subunits.

PMID- 20817756
TI  - The effects of affinity and valency of an albumin-binding domain (ABD) on the
      half-life of a single-chain diabody-ABD fusion protein.
AB  - Fusion of small recombinant antibody fragments to an albumin-binding domain (ABD)
      from streptococcal protein G strongly extends their plasma half-life. This ABD
      binds with nanomolar affinity to human (HSA) and mouse serum albumin (MSA). It
      was speculated that an increase in albumin-binding affinity should lead to a
      further increase in half-life. In the present study, we analyzed the effects of
      affinity and valency of the ABD on the pharmacokinetic properties of a bispecific
      single-chain diabody (scDb), applied previously to investigate various half-life
      extension strategies. The scDb is directed against carcinoembryonic antigen (CEA)
      and CD3 capable of mediating T cell retargeting to tumor cells. Two scDb
      derivatives with increased (scDb-ABD-H) and decreased (scDb-ABD-L) affinity as
      well as an scDb molecule fused to two ABD (scDb-ABD(2)) were generated and
      produced in mammalian cells. The altered binding of these constructs to HSA and
      MSA was confirmed by ELISA and quartz crystal microbalance measurements. All
      constructs bound efficiently to CEA and CD3-positive cells and were able to
      activate T cells in a target cell-dependent manner, although T cell activation
      was reduced in the presence of serum albumin. All three derivatives showed a
      strongly increased half-life in mice as compared with scDb. Compared with the
      wild-type scDb-ABD, the half-life of scDb-ABD-H exhibited a prolonged half-life
      and scDb-ABD-L a reduced half-life, while the half-life scDb-ABD(2) was almost
      identical to that of scDb-ABD. However, these changes were only moderate,
      indicating that the half-life-extending property of the ABD in mice is only
      weakly influenced by affinity for serum albumin or valency of albumin binding.

PMID- 20817757
TI  - Expression of soluble, active fragments of the morphogenetic protein SpoIIE from
      Bacillus subtilis using a library-based construct screen.
AB  - SpoIIE is a dual function protein that plays important roles during sporulation
      in Bacillus subtilis. It binds to the tubulin-like protein FtsZ causing the cell
      division septum to relocate from mid-cell to the cell pole, and it
      dephosphorylates SpoIIAA phosphate leading to establishment of differential gene
      expression in the two compartments following the asymmetric septation. Its 872
      residue polypeptide contains a multiple-membrane spanning sequence at the N
      terminus and a PP2C phosphatase domain at the C-terminus. The central segment
      that binds to FtsZ is unlike domains of known structure or function, moreover the
      domain boundaries are poorly defined and this has hampered the expression of
      soluble fragments of SpoIIE at the levels required for structural studies. Here
      we have screened over 9000 genetic constructs of spoIIE using a random
      incremental truncation library approach, ESPRIT, to identify a number of soluble
      C-terminal fragments of SpoIIE that were aligned with the protein sequence to map
      putative domains and domain boundaries. The expression and purification of three
      fragments were optimised, yielding multimilligram quantities of the PP2C
      phosphatase domain, the putative FtsZ-binding domain and a larger fragment
      encompassing both these domains. All three fragments are monomeric and the PP2C
      domain-containing fragments have phosphatase activity.

PMID- 20817758
TI  - Engineering extended membrane scaffold proteins for self-assembly of soluble
      nanoscale lipid bilayers.
AB  - High-density lipoproteins (HDLs) play an important role in human health through
      the metabolism and trafficking of cholesterol as well as providing the feedstocks
      for steroid hormone biosynthesis. These particles contain proteins, primarily Apo
      AI and phospholipid and progress through various structural forms including
      'lipid-poor', 'discoidal' and 'spherical' entities as cholesterol esters and
      lipid are incorporated. The discoidal form of HDL is stabilized in solution by
      two encircling belts of Apo-AI. Previous protein engineering of the Apo-AI
      sequence has led to a series of amphipathic helical proteins, termed membrane
      scaffold proteins (MSPs), which have shown great value in assembling nanoscale
      soluble membrane bilayers, termed Nanodiscs, of homogeneous size and composition
      and in the assembly of numerous integral membrane proteins for biophysical and
      biochemical investigations. In this communication we document a protein
      engineering approach to generate and optimize an extended polypeptide MSP, which
      will self-assemble phospholipids into larger Nanodiscs with diameters of 16-17
      nm. We extensively characterize these structures by size exclusion chromatography
      and solution X-ray scattering.

PMID- 20817760
TI  - Absorption and metabolization of cytoprotective epicatechin thio conjugates in
      rats.
AB  - The epicatechin (EC) thio derivatives 4beta-(S-cysteinyl)-epicatechin (Cys-EC)
      and 4beta-(S-cysteaminyl)-epicatechin (Cya-EC) are compounds that may provide
      protection from oxidation via mechanisms involving either the flavonoid moiety or
      the nonphenolic cysteine or cysteamine part of the molecule. Because the
      metabolically modified molecules may be the actual active species, we estimated
      the absorption/metabolization of the thio derivatives through the small intestine
      in vitro and studied the body distribution of the compounds and their metabolites
      in rats. The analysis of the samples generated was done using a high-performance
      liquid chromatograph coupled to a UV detector and a tandem mass spectrometer. We
      show that Cya-EC follows the same phase II metabolization pattern as EC, whereas
      Cys-EC is transported with the intact catechol moiety through the small intestine
      and effectively metabolized systemically. We also found that Cya-EC generates Cys
      EC in vivo, which provides evidence for a Cya-EC-mediated cytoprotective effect
      through cysteamine/cystine exchange with subsequent cysteine transport,
      ubiquitously throughout the organism.

PMID- 20817759
TI  - Nuclear receptor engineering based on novel structure activity relationships
      revealed by farnesyl pyrophosphate.
AB  - Nuclear receptors (NRs) comprise the second largest protein family targeted by
      currently available drugs, acting via specific ligand interactions within the
      ligand binding domain (LBD). Recently, farnesyl pyrophosphate (FPP) was shown to
      be a unique promiscuous NR ligand, activating a subset of NR family members and
      inhibiting wound healing in skin. The current study aimed at visualizing the
      unique basis of FPP interaction with multiple receptors in order to identify
      general structure-activity relationships that operate across the NR family.
      Docking of FPP to the 3D structures of the LBDs of a diverse set of NRs
      consistently revealed an electrostatic FPP pyrophosphate contact with an NR
      arginine conserved in the NR family, a hydrophobic farnesyl contact with NR helix
      12 and a ligand binding pocket volume between 300 and 430 A(3) as the minimal
      requirements for FPP activation of any NR. Lack of any of these structural
      features appears to render a given NR resistant to FPP activation. We used these
      structure-activity relationships to rationally design and successfully engineer
      several mutant human estrogen receptors that retain responsiveness to estradiol
      but no longer respond to FPP.

PMID- 20817761
TI  - Single nucleotide polymorphisms within the bovine DLK1-DIO3 imprinted domain are
      associated with economically important production traits in cattle.
AB  - Previous studies show that DNA sequence variation within the mammalian DLK1-DIO3
      imprinted domain influences production traits in domestic livestock, most notably
      the ovine callipyge phenotype. We assessed genotype-phenotype associations
      between 7 single nucleotide polymorphisms (SNPs) within the orthologous bovine
      DLK1-DIO3 domain and performance traits in 848 progeny-tested Holstein-Friesian
      dairy sires. One SNP (MEG3_01) located proximal to the maternally expressed 3
      (MEG3/Gtl2) gene was associated with milk yield, subcutaneous fat levels, and
      progeny carcass conformation (P <= 0.01) and also tended to be associated with
      milk fat and protein yield (P <= 0.10). A single SNP (CLPG_01) within the
      putative CLPG1 locus was associated with progeny carcass fat (P <= 0.05), whereas
      a single SNP (PEG11_01) located proximal to the paternally expressed 11
      (PEG11/Rtl) gene was associated with progeny carcass weight (P <= 0.05). The
      MEG3_01 SNP together with an additional 2 SNPs (MEG8_01 and MEG8_02) located
      proximal to the putative maternally expressed 8 (MEG8/Rian) ortholog were
      associated (P <= 0.05) with perinatal mortality. Finally, one SNP (MEG3_03) was
      associated (P <= 0.05) with gestation length, whereas both the CLPG_01 and
      MEG8_01 SNPs also tended to be associated with calving interval (P <= 0.10).
      Linkage disequilibrium analysis suggests that some phenotypic associations
      observed at these loci are independent. To our knowledge, this is one of the
      first studies demonstrating associations between the bovine DLK1-DIO3 domain and
      milk, carcass, fertility and, health traits in cattle. This imprinted domain may
      serve as a potential target for future genetic selection strategies.

PMID- 20817762
TI  - Patients with primary hyperparathyroidism have lower circulating sclerostin
      levels than euparathyroid controls.
AB  - OBJECTIVE: In vitro and in vivo studies in animal models have shown that
      parathyroid hormone (PTH) inhibits the expression of the SOST gene, which encodes
      sclerostin, an osteocyte-derived negative regulator of bone formation. We tested
      the hypothesis that chronic PTH excess decreases circulating sclerostin in
      humans. DESIGN: We studied 25 patients with elevated serum PTH concentrations due
      to primary hyperparathyroidism (PHPT) and 49 patients cured from PHPT after
      successful parathyroidectomy (PTx; euparathyroid controls (EuPTH)). METHODS: We
      measured plasma PTH and serum sclerostin levels and the serum markers of bone
      turnover alkaline phosphatase, P1NP, and beta-CTX. RESULTS: As expected by the
      design of the study, mean plasma PTH was significantly higher (P<0.001) in PHPT
      patients (15.3 pmol/l; 95% confidence interval (CI): 11.1-19.5) compared with
      that of EuPTH controls (4.1 pmol/l; 95% CI: 3.6-4.5). PHPT patients had
      significantly lower serum sclerostin values compared with those in EuPTH subjects
      (30.5 pg/ml; 95% CI: 26.0-35.1 vs 45.4 pg/ml; 95% CI: 40.5-50.2; P<0.001) and
      healthy controls (40.0 pg/ml; 95% CI: 37.1-42.9; P=0.01). Plasma PTH
      concentrations were negatively correlated with serum sclerostin values (r=-0.44;
      P<0.001). Bone turnover markers were significantly correlated with PTH, but not
      with sclerostin. CONCLUSION: Patients with PHPT have significantly lower serum
      sclerostin values compared with PTx controls with normal PTH concentrations. The
      negative correlation between PTH and sclerostin suggests that SOST is
      downregulated by PTH in humans.

PMID- 20817763
TI  - Polymorphic DNA repair and metabolic genes: a multigenic study on gastric cancer.
AB  - Risk factors for gastric cancer (GC) include inter-individual variability in the
      inflammatory response to Helicobacter pylori infection, in the ability of
      detoxifying DNA reactive species and repairing DNA damage generated by oxidative
      stress and dietary carcinogens. To evaluate the association between polymorphic
      DNA repair genes and GC risk, a case-control study including 314 histologically
      confirmed GC patients and 548 healthy controls was conducted in a GC high-risk
      area in Tuscany, Italy. Polymorphic variants of base excision repair (APE1-D148E,
      XRCC1-R194W, XRCC1-R399Q and OGG1-S326C), nucleotide excision repair (XPC-PAT,
      XPA-23G>A, ERCC1-19007T>C and XPD-L751Q), recombination (XRCC3-T241M) and
      alkylation damage reversal (MGMT-L84F) were tested for their potential role in
      the development of GC by using logistic regression models. The same population
      was also characterised for GSTT1 and GSTM1 variant alleles to search for possible
      functional interactions between metabolic and DNA repair genotypes by two-way
      interactions using multivariate logistic models. No significant association
      between any single DNA repair genotype and GC risk was detected with a borderline
      association with the XPC-PAT homozygous genotype [odds ratio (OR) =1.42; 95%
      confidence interval (CI) 0.94-2.17]. Gene-gene interaction analysis revealed
      combinations of unfavourable genotypes involving either multiple DNA repair
      polymorphisms or DNA repair and GST-specific genotypes. The combination of the
      XPC-PAT and the XPA variant alleles significantly increased GC risk (OR=2.15; 95%
      CI 1.17-3.93, P=0.0092). A significant interaction was also found between the
      APE1 wild-type genotype and either the single GSTT1 (OR=4.90; 95% CI 2.38-10.11,
      P=0.0079) or double GSTM1-GSTT1 null (OR=7.84; 95% CI 3.19-19.22, P=0.0169)
      genotypes or the XPA-mutant allele (OR=3.56; 95% CI 1.53-8.25, P=0.0012). These
      findings indicate that a complex interaction between host factors such as
      oxidative stress, antioxidant capacity and efficiency of multiple DNA repair
      pathways underlies the inter-individual variability in GC risk.

PMID- 20817765
TI  - The anti-anti-sigma factor BldG is involved in activation of the stress response
      sigma factor sigma(H) in Streptomyces coelicolor A3(2).
AB  - The alternative stress response sigma factor sigma(H) has a role in regulation of
      the osmotic stress response and in morphological differentiation in Streptomyces
      coelicolor A3(2). Its gene, sigH, is located in an operon with the gene that
      encodes its anti-sigma factor UshX (PrsH). However, no gene with similarity to an
      anti-anti-sigma factor which may have a role in sigma(H) activation by a "partner
      switching" mechanism is located in the operon. By using a combination of several
      approaches, including pull-down and bacterial two-hybrid assays and visualization
      of the complex by native polyacrylamide electrophoresis, we demonstrated a direct
      interaction between UshX and the pleiotropic sporulation-specific anti-anti-sigma
      factor BldG. Osmotic induction of transcription of the sigHp2 promoter that is
      specifically recognized by RNA polymerase containing sigma(H) was absent in an S.
      coelicolor bldG mutant, indicating a role of BldG in sigma(H) activation by a
      partner-switching-like mechanism.

PMID- 20817764
TI  - Characterization of a two-component regulatory system that regulates succinate
      mediated catabolite repression in Sinorhizobium meliloti.
AB  - When they are available, Sinorhizobium meliloti utilizes C(4)-dicarboxylic acids
      as preferred carbon sources for growth while suppressing the utilization of some
      secondary carbon sources such as alpha- and beta-galactosides. The phenomenon of
      using succinate as the sole carbon source in the presence of secondary carbon
      sources is termed succinate-mediated catabolite repression (SMCR). Genetic
      screening identified the gene sma0113 as needed for strong SMCR when S. meliloti
      was grown in succinate plus lactose, maltose, or raffinose. sma0113 and the gene
      immediately downstream, sma0114, encode the proteins Sma0113, an HWE histidine
      kinase with five PAS domains, and Sma0114, a CheY-like response regulator lacking
      a DNA-binding domain. sma0113 in-frame deletion mutants show a relief of
      catabolite repression compared to the wild type. sma0114 in-frame deletion
      mutants overproduce polyhydroxybutyrate (PHB), and this overproduction requires
      sma0113. Sma0113 may use its five PAS domains for redox level or energy state
      monitoring and use that information to regulate catabolite repression and related
      responses.

PMID- 20817766
TI  - Novel rhamnosyltransferase involved in biosynthesis of serovar 4-specific
      glycopeptidolipid from Mycobacterium avium complex.
AB  - Glycopeptidolipids (GPLs) are one of the major glycolipid components present on
      the surface of Mycobacterium avium complex (MAC) that belong to opportunistic
      pathogens distributed in the natural environment. The serovars of MAC, up to
      around 30 types, are defined by the variable oligosaccharide portions of the
      GPLs. Epidemiological studies show that serovar 4 is the most prevalent type, and
      the prognosis of pulmonary disease caused by serovar 4 is significantly worse
      than that caused by other serovars. However, little is known about the
      biosynthesis of serovar 4-specific GPL, particularly the formation of the
      oligosaccharide portion that determines the properties of serovar 4. To
      investigate the biosynthesis of serovar 4-specific GPL, we focused on one segment
      that included functionally unknown genes in the GPL biosynthetic gene cluster of
      a serovar 4 strain. In this segment, a putative hemolytic protein gene, hlpA, and
      its downstream gene were found to be responsible for the formation of the 4-O
      methyl-rhamnose residue, which is unique to serovar 4-specific GPL. Moreover,
      functional characterization of the hlpA gene revealed that it encodes a
      rhamnosyltransferase that transfers a rhamnose residue via 1->4 linkage to a
      fucose residue of serovar 2-specific GPL, which is a key pathway leading to the
      synthesis of oligosaccharide of serovar 4-specific GPL. These findings may
      provide clues to understanding the biological role of serovar 4-specific GPL in
      MAC pathogenicity and may also provide new insights into glycosyltransferase,
      which generates structural and functional diversity of GPLs.

PMID- 20817767
TI  - Regulation of the biosynthesis of the macrolide antibiotic spiramycin in
      Streptomyces ambofaciens.
AB  - Streptomyces ambofaciens synthesizes the macrolide antibiotic spiramycin. The
      biosynthetic gene cluster for spiramycin has been characterized for S.
      ambofaciens. In addition to the regulatory gene srmR (srm22), previously
      identified (M. Geistlich et al., Mol. Microbiol. 6:2019-2029, 1992), three
      putative regulatory genes had been identified by sequence analysis. Gene
      expression analysis and gene inactivation experiments showed that only one of
      these three genes, srm40, plays a major role in the regulation of spiramycin
      biosynthesis. The disruption of srm22 or srm40 eliminated spiramycin production
      while their overexpression increased spiramycin production. Expression analysis
      was performed by reverse transcription-PCR (RT-PCR) for all the genes of the
      cluster in the wild-type strain and in the srm22 (srmR) and srm40 deletion
      mutants. The results from the expression analysis, together with the ones from
      the complementation experiments, indicated that Srm22 is required for srm40
      expression, Srm40 being a pathway-specific activator that controls most, if not
      all, of the spiramycin biosynthetic genes.

PMID- 20817768
TI  - Complete genome sequence of the representative gamma-hexachlorocyclohexane
      degrading bacterium Sphingobium japonicum UT26.
AB  - Sphingobium japonicum strain UT26 utilizes gamma-hexachlorocyclohexane (gamma
      HCH), a man-made chlorinated pesticide that causes serious environmental problems
      due to its toxicity and long persistence, as a sole source of carbon and energy.
      Here, we report the complete genome sequence of UT26, which consists of two
      chromosomes and three plasmids. The 15 lin genes involved in gamma-HCH
      degradation are dispersed on the two chromosomes and one of the three plasmids.

PMID- 20817769
TI  - RNA polymerase trafficking in Bacillus subtilis cells.
AB  - To obtain insight into the in vivo dynamics of RNA polymerase (RNAP) on the
      Bacillus subtilis genome, we analyzed the distribution of the sigma(A) and beta'
      subunits of RNAP and the NusA elongation factor on the genome in exponentially
      growing cells using chromatin affinity precipitation coupled with gene chip
      mapping (ChAP-chip). In contrast to Escherichia coli RNAP, which often
      accumulates at the promoter-proximal region, B. subtilis RNuAlphaP is evenly
      distributed from the promoter to the coding sequences. This finding suggests
      that, in general, B. subtilis RNAP recruited to the promoter promptly
      translocates away from the promoter to form the elongation complex and proceeds
      without intragenic transcription attenuation. We detected RNAP accumulation in
      the promoter-proximal regions of some genes, most of which can be identified as
      transcription attenuation systems in the leader region. Our findings suggest that
      the differences in RNAP behavior between E. coli and B. subtilis during
      initiation and elongation steps might result in distinct strategies for
      postinitiation control of transcription. The E. coli mechanism involves trapping
      at the promoter and promoter-proximal pausing of RNAP in addition to
      transcription attenuation, whereas transcription attenuation in leader sequences
      is mainly employed in B. subtilis.

PMID- 20817770
TI  - Role of surface protein SasG in biofilm formation by Staphylococcus aureus.
AB  - The SasG surface protein of Staphylococcus aureus has been shown to promote the
      formation of biofilm. SasG comprises an N-terminal A domain and repeated B
      domains. Here we demonstrate that SasG is involved in the accumulation phase of
      biofilm, a process that requires a physiological concentration of Zn(2+). The B
      domains, but not the A domain, are required. Purified recombinant B domain
      protein can form dimers in vitro in a Zn(2+)-dependent fashion. Furthermore, the
      protein can bind to cells that have B domains anchored to their surface and block
      biofilm formation. The full-length SasG protein exposed on the cell surface is
      processed within the B domains to a limited degree, resulting in cleaved proteins
      of various lengths being released into the supernatant. Some of the released
      molecules associate with the surface-exposed B domains that remain attached to
      the cell. Studies using inhibitors and mutants failed to identify any protease
      that could cause the observed cleavage within the B domains. Extensively purified
      recombinant B domain protein is very labile, and we propose that cleavage occurs
      spontaneously at labile peptide bonds and that this is necessary for biofilm
      formation.

PMID- 20817771
TI  - Transcriptomic and phenotypic characterization of a Bacillus subtilis strain
      without extracytoplasmic function sigma factors.
AB  - Bacillus subtilis encodes seven extracytoplasmic function (ECF) sigma factors.
      Three (sigma(M), sigma(W), and sigma(X)) mediate responses to cell envelope
      active antibiotics. The functions of sigma(V), sigma(Y), sigma(Z), and
      sigma(YlaC) remain largely unknown, and strong inducers of these sigma factors
      and their regulons have yet to be defined. Here, we define transcriptomic and
      phenotypic differences under nonstress conditions between a strain carrying
      deletions in all seven ECF sigma factor genes (the Delta7ECF mutant), a DeltaMWX
      triple mutant, and the parental 168 strain. Our results identify >80 genes as at
      least partially dependent on ECF sigma factors, and as expected, most of these
      are dependent on sigma(M), sigma(W), or sigma(X), which are active at a
      significant basal level during growth. Several genes, including the eps operon
      encoding enzymes for exopolysaccharide (EPS) production, were decreased in
      expression in the Delta7ECF mutant but affected less in the DeltaMWX mutant.
      Consistent with this observation, the Delta7ECF mutant (but not the DeltaMWX
      mutant) showed reduced biofilm formation. Extending previous observations, we
      also note that the DeltaMWX mutant is sensitive to a variety of antibiotics and
      the Delta7ECF mutant is either as sensitive as, or slightly more sensitive than,
      the DeltaMWX strain to these stressors. These findings emphasize the overlapping
      nature of the seven ECF sigma factor regulons in B. subtilis, confirm that three
      of these (sigma(M), sigma(W), and sigma(X)) play the dominant role in conferring
      intrinsic resistance to antibiotics, and provide initial insights into the roles
      of the remaining ECF sigma factors.

PMID- 20817772
TI  - Activation of the Pseudomonas aeruginosa AlgU regulon through mucA mutation
      inhibits cyclic AMP/Vfr signaling.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that causes acute, invasive
      infections in immunocompromised individuals and chronic, persistent respiratory
      infections in individuals with cystic fibrosis (CF). The differential progression
      of acute or chronic infections involves the production of distinct sets of
      virulence factors. P. aeruginosa strains isolated from patients with acute
      respiratory infection are generally nonencapsulated and express a variety of
      invasive virulence factors, including flagella, the type III secretion system
      (T3SS), type IV pili (TFP), and multiple secreted toxins and degradative enzymes.
      Strains isolated from chronically infected CF patients, however, typically lack
      expression of invasive virulence factors and have a mucoid phenotype due to the
      production of an alginate capsule. The mucoid phenotype results from loss-of
      function mutations in mucA, which encodes an anti-sigma factor that normally
      prevents alginate synthesis. Here, we report that the cyclic AMP/Vfr-dependent
      signaling (CVS) pathway is defective in mucA mutants and that the defect occurs
      at the level of vfr expression. The CVS pathway regulates the expression of
      multiple invasive virulence factors, including T3SS, exotoxin A, protease IV, and
      TFP. We further demonstrate that mucA-dependent CVS inhibition involves the
      alternative sigma factor AlgU (AlgT) and the response regulator AlgR but does not
      depend on alginate production. Our findings show that a single naturally
      occurring mutation leads to inverse regulation of virulence factors involved in
      acute and persistent infections. These results suggest that mucoid conversion and
      inhibition of invasive virulence determinants may both confer a selective
      advantage to mucA mutant strains of P. aeruginosa in the CF lung.

PMID- 20817773
TI  - A conserved acetyl esterase domain targets diverse bacteriophages to the Vi
      capsular receptor of Salmonella enterica serovar Typhi.
AB  - A number of bacteriophages have been identified that target the Vi capsular
      antigen of Salmonella enterica serovar Typhi. Here we show that these Vi phages
      represent a remarkably diverse set of phages belonging to three phage families,
      including Podoviridae and Myoviridae. Genome analysis facilitated the further
      classification of these phages and highlighted aspects of their independent
      evolution. Significantly, a conserved protein domain carrying an acetyl esterase
      was found to be associated with at least one tail fiber gene for all Vi phages,
      and the presence of this domain was confirmed in representative phage particles
      by mass spectrometric analysis. Thus, we provide a simple explanation and
      paradigm of how a diverse group of phages target a single key virulence antigen
      associated with this important human-restricted pathogen.

PMID- 20817774
TI  - New insights into the shikimate and aromatic amino acids biosynthesis pathways in
      plants.
AB  - The aromatic amino acids phenylalanine, tyrosine, and tryptophan in plants are
      not only essential components of protein synthesis, but also serve as precursors
      for a wide range of secondary metabolites that are important for plant growth as
      well as for human nutrition and health. The aromatic amino acids are synthesized
      via the shikimate pathway followed by the branched aromatic amino acids
      biosynthesis pathway, with chorismate serving as a major intermediate branch
      point metabolite. Yet, the regulation and coordination of synthesis of these
      amino acids are still far from being understood. Recent studies on these pathways
      identified a number of alternative cross-regulated biosynthesis routes with
      unique evolutionary origins. Although the major route of Phe and Tyr biosynthesis
      in plants occurs via the intermediate metabolite arogenate, recent studies
      suggest that plants can also synthesize phenylalanine via the intermediate
      metabolite phenylpyruvate (PPY), similarly to many microorganisms. Recent studies
      also identified a number of transcription factors regulating the expression of
      genes encoding enzymes of the shikimate and aromatic amino acids pathways as well
      as of multiple secondary metabolites derived from them in Arabidopsis and in
      other plant species.

PMID- 20817775
TI  - Genome-wide analysis of novel splice variants induced by topoisomerase I
      poisoning shows preferential occurrence in genes encoding splicing factors.
AB  - RNA splicing is required to remove introns from pre-mRNA, and alternative
      splicing generates protein diversity. Topoisomerase I (Top1) has been shown to be
      coupled with splicing by regulating serine/arginine-rich splicing proteins. Prior
      studies on isolated genes also showed that Top1 poisoning by camptothecin (CPT),
      which traps Top1 cleavage complexes (Top1cc), can alter RNA splicing. Here, we
      tested the effect of Top1 inhibition on splicing at the genome-wide level in
      human colon carcinoma HCT116 and breast carcinoma MCF7 cells. The RNA of HCT116
      cells treated with CPT for various times was analyzed with ExonHit Human Splice
      Array. Unlike other exon array platforms, the ExonHit arrays include junction
      probes that allow the detection of splice variants with high sensitivity and
      specificity. We report that CPT treatment preferentially affects the splicing of
      splicing-related factors, such as RBM8A, and generates transcripts coding for
      inactive proteins lacking key functional domains. The splicing alterations
      induced by CPT are not observed with cisplatin or vinblastine and are not simply
      due to reduced Top1 activity, as Top1 downregulation by short interfering RNA did
      not alter splicing like CPT treatment. Inhibition of RNA polymerase II (Pol II)
      hyperphosphorylation by 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRB)
      blocked the splicing alteration induced by CPT, which suggests that the rapid Pol
      II hyperphosphorylation induced by CPT interferes with normal splicing. The
      preferential effect of CPT on genes encoding splicing factors may explain the
      abnormal splicing of a large number of genes in response to Top1cc.

PMID- 20817776
TI  - Human mesenchymal stem cells suppress chronic airway inflammation in the murine
      ovalbumin asthma model.
AB  - Allogeneic human mesenchymal stem cells (hMSCs) introduced intravenously can have
      profound anti-inflammatory activity resulting in suppression of graft vs. host
      disease as well as regenerative events in the case of stroke, infarct, spinal
      cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart
      disease in human and animal models of these diseases. hMSCs produce bioactive
      factors that provide molecular cuing for: 1) immunosuppression of T cells; 2)
      antiscarring; 3) angiogenesis; 4) antiapoptosis; and 5) regeneration (i.e.,
      mitotic for host-derived progenitor cells). Studies have shown that hMSCs have
      profound effects on the immune system and are well-tolerated and therapeutically
      active in immunocompetent rodent models of multiple sclerosis and stroke.
      Furthermore, intravenous administration of MSCs results in pulmonary
      localization. Asthma is a major debilitating pulmonary disease that impacts in
      excess of 150 million people in the world with uncontrolled asthma potentially
      leading to death. In addition, the socioeconomic impact of asthma-associated
      illnesses at the pediatric and adult level are in the millions of dollars in
      healthcare costs and lost days of work. hMSCs may provide a viable multiaction
      therapeutic for this inflammatory lung disease by secreting bioactive factors or
      directing cellular activity. Our studies show the effectiveness and specificity
      of the hMSCs on decreasing chronic airway inflammation associated with the murine
      ovalbumin model of asthma. In addition, the results from these studies verify the
      in vivo immunoeffectiveness of hMSCs in rodents and support the potential
      therapeutic use of hMSCs for the treatment of airway inflammation associated with
      chronic asthma.

PMID- 20817777
TI  - Role of LTB4 in the pathogenesis of elastase-induced murine pulmonary emphysema.
AB  - Exaggerated levels of the leukotriene B4 (LTB4) frequently coexist at sites of
      inflammation and tissue remodeling. Therefore, we hypothesize that the LTB4
      pathway plays an important role in the pathogenesis of neutrophilic inflammation
      that contributes to pulmonary emphysema. In this study, significant levels of
      LTB4 were detected in human lung tissues with emphysema compared with lungs
      without emphysema (9,497 +/- 2,839 vs. 4,142 +/- 1,173 pg/ml, n = 9 vs. 10, P =
      0.04). To further determine the biological role of LTB4 in the pathogenesis of
      emphysema, we compared the lungs of wild-type (WT) and LTA4 hydrolase-/- mice
      (LTB4 deficient, LTA4H-/-) exposed to intranasal elastase or vehicle control. We
      found that intranasal elastase induced accumulation of LTB4 in the lungs and
      caused progressively worsening emphysema between 14 and 28 days after elastase
      exposure in WT mice but not in LTA4H-/- mice. Premortem physiology documented
      increased lung compliance in elastase-exposed WT mice compared with elastase
      exposed LTA4H-/- mice as measured by Flexivent (0.058 +/- 0.005 vs. 0.041 +/-
      0.002 ml/cmH2O pressure). Postmortem morphometry documented increased total lung
      volume and alveolar sizes in elastase-exposed WT mice compared with elastase
      exposed LTA4H-/- mice as measured by volume displacement and alveolar chord
      length assessment. Furthermore, elastase-exposed LTA4H-/- mice were found to have
      significantly delayed influx of the CD45(high)CD11b(high)Ly6G(high) leukocytes
      compatible with neutrophils compared with elastase-exposed WT mice. Mechanistic
      insights to these phenotypes were provided by demonstrating protection from
      elastase-induced murine emphysema with neutrophil depletion in the elastase
      exposed WT mice and by demonstrating time-dependent modulation of cysteinyl
      leukotriene biosynthesis in the elastase-exposed LTA4H-/- mice compared with
      elastase-exposed WT mice. Together, these findings demonstrated that LTB4 played
      an important role in promoting the pathogenesis of pulmonary emphysema associated
      with neutrophilic pulmonary inflammation.

PMID- 20817779
TI  - Logarithmic superposition of force response with rapid length changes in relaxed
      porcine airway smooth muscle.
AB  - We present a systematic quantitative analysis of power-law force relaxation and
      investigate logarithmic superposition of force response in relaxed porcine airway
      smooth muscle (ASM) strips in vitro. The term logarithmic superposition describes
      linear superposition on a logarithmic scale, which is equivalent to
      multiplication on a linear scale. Additionally, we examine whether the dynamic
      response of contracted and relaxed muscles is dominated by cross-bridge cycling
      or passive dynamics. The study shows the following main findings. For relaxed
      ASM, the force response to length steps of varying amplitude (0.25-4% of
      reference length, both lengthening and shortening) are well-fitted with power-law
      functions over several decades of time (10-2 to 103 s), and the force response
      after consecutive length changes is more accurately fitted assuming logarithmic
      superposition rather than linear superposition. Furthermore, for sinusoidal
      length oscillations in contracted and relaxed muscles, increasing the oscillation
      amplitude induces greater hysteresivity and asymmetry of force-length
      relationships, whereas increasing the frequency dampens hysteresivity but
      increases asymmetry. We conclude that logarithmic superposition is an important
      feature of relaxed ASM, which may facilitate a more accurate prediction of force
      responses in the continuous dynamic environment of the respiratory system. In
      addition, the single power-function response to length changes shows that the
      dynamics of cross-bridge cycling can be ignored in relaxed muscle. The similarity
      in response between relaxed and contracted states implies that the investigated
      passive dynamics play an important role in both states and should be taken into
      account.

PMID- 20817778
TI  - Modulation of lung inflammation by the Epstein-Barr virus protein Zta.
AB  - Several studies have implicated gamma-herpesviruses, particularly Epstein-Barr
      virus (EBV), in the progression of idiopathic pulmonary fibrosis. The data
      presented here examine the possible role that EBV plays in the potentiation of
      this disease by evaluating the pulmonary response to expression of the EBV lytic
      transactivator protein Zta. Expression of Zta in the lungs of mice via adenovirus
      mediated delivery (Adv-Zta) produced profibrogenic inflammation that appeared
      most pronounced by day 7 postexposure. Relative to mice exposed to control GFP
      expressing adenovirus (Adv-GFP), mice exposed to Adv-Zta displayed evidence of
      lung injury and a large increase in inflammatory cells, predominantly
      neutrophils, recovered by bronchoalveolar lavage (BAL). Cytokine and mRNA
      profiling of the BAL fluid and cells recovered from Adv-Zta-treated mice revealed
      a Th2 and Th17 bias. mRNA profiles from Adv-Zta-infected lung epithelial cells
      revealed consistent induction of mRNAs encoding Th2 cytokines. Coexpression in
      transient assays of wild-type Zta, but not a DNA-binding-defective mutant Zta,
      activated expression of the IL-13 promoter in lung epithelial cells, and
      detection of IL-13 in Adv-Zta-treated mice correlated with expression of Zta.
      Induction of Th2 cytokines in Zta-expressing mice corresponded with alternative
      activation of macrophages. In cell culture and in mice, Zta repressed lung
      epithelial cell markers. Despite the profibrogenic character at day 7, the
      inflammation resolves by 28 days postexposure to Adv-Zta without evidence of
      fibrosis. These observations indicate that the EBV lytic transactivator protein
      Zta displays activity consistent with a pathogenic role in pulmonary fibrosis
      associated with herpesvirus infection.

PMID- 20817781
TI  - Are coarse scales sufficient for fast detection of visual threat?
AB  - It has recently been suggested that low-spatial-frequency information would
      provide rapid visual cues to the amygdala for basic but ultrarapid behavioral
      responses to dangerous stimuli. The present behavioral study investigated the
      role of different spatial-frequency channels in visually detecting dangerous
      stimuli belonging to living or nonliving categories. Subjects were engaged in a
      visual detection task involving dangerous stimuli, and subjects' behavioral
      responses were assessed in association with their fear expectations (induced by
      an aversive 90-dB white noise). Our results showed that, despite its crudeness,
      low-spatial-frequency information could constitute a sufficient signal for fast
      recognition of visual danger in a context of fear expectation. In addition, we
      found that this effect tended to be specific for living entities. These results
      were obtained despite a strong perceptual bias toward faster recognition of high
      spatial-frequency stimuli under supraliminal perception durations.

PMID- 20817780
TI  - Right orbitofrontal cortex mediates conscious olfactory perception.
AB  - Understanding how the human brain translates sensory impressions into conscious
      percepts is a key challenge of neuroscience research. Work in this area has
      overwhelmingly centered on the conscious experience of vision at the exclusion of
      the other senses--in particular, smell. We hypothesized that the orbitofrontal
      cortex (OFC) is a central substrate for olfactory conscious experience because of
      its privileged physiological role in odor processing. Combining functional
      magnetic resonance imaging, peripheral autonomic recordings, and olfactory
      psychophysics, we studied a case of complete anosmia (smell loss) in a patient
      with circumscribed traumatic brain injury to the right OFC. Despite a complete
      absence of conscious olfaction, the patient exhibited robust "blind smell," as
      indexed by reliable odor-evoked neural activity in the left OFC and normal
      autonomic responses to odor hedonics during presentation of stimuli to the left
      nostril. These data highlight the right OFC's critical role in subserving human
      olfactory consciousness.

PMID- 20817782
TI  - Dirty hands and dirty mouths: embodiment of the moral-purity metaphor is specific
      to the motor modality involved in moral transgression.

PMID- 20817783
TI  - Company, country, connections: counterfactual origins increase organizational
      commitment, patriotism, and social investment.
AB  - Four studies examined the relationship between counterfactual origins--thoughts
      about how the beginning of organizations, countries, and social connections might
      have turned out differently--and increased feelings of commitment to those
      institutions and connections. Study 1 found that counterfactually reflecting on
      the origins of one's country increases patriotism. Study 2 extended this finding
      to organizational commitment and examined the mediating role of poignancy. Study
      3 found that counterfactual reflection boosts organizational commitment even
      beyond the effects of other commitment-enhancing appeals and that perceptions of
      fate mediate the positive effect of counterfactual origins on commitment.
      Finally, Study 4 temporally separated the counterfactual manipulation from a
      behavioral measure of commitment and found that counterfactual reflection
      predicted whether participants e-mailed social contacts 2 weeks later. The robust
      relationship between counterfactual origins and commitment was found across a
      wide range of companies and countries, with undergraduates and M.B.A. students,
      and for attitudes and behaviors.

PMID- 20817784
TI  - Evaluation of a novel isotope biomarker for dietary consumption of sweets.
AB  - Carbon isotopic signatures ("delta13C") might reflect consumption of corn- and
      cane-based sweeteners. The authors hypothesized that the delta13C value of human
      serum is higher for individuals with high versus low intakes of corn- and cane
      based sweeteners (measured as sweetened beverage intake). They conducted a cross
      sectional study within the Atherosclerosis Risk in Communities Magnetic Resonance
      Imaging study (Maryland, 2005-2006). Diet was assessed by food frequency
      questionnaire, and blinded serum samples were assayed by natural abundance stable
      isotope mass spectroscopy. Studied were 186 participants (53% male; mean age, 71
      years; mean body mass index, 30 kg/m2). Serum delta13C values for individuals
      with high sweetened beverage intakes were significantly higher than for those
      with low intakes (-19.150/00 vs. -19.470/00, P < 0.001). Serum delta13C value
      increased 0.200/00 for every serving/day of sweetened beverages (P < 0.01). The
      association between sweetened beverages and serum delta13C value remained
      significant after adjustment for confounding by corn-based product intake (P <
      0.001). Serum delta13C values were also associated with waist circumference, body
      mass index, and waist-to-hip ratio. This study provides the first known evidence
      that the delta13C value of human serum differs between persons consuming low and
      high amounts of sweets. Within the proper framework, serum delta13C value could
      be developed into an objective biomarker promoting more reliable assessment of
      dietary sweets intake.

PMID- 20817785
TI  - Mapping health data: improved privacy protection with donut method geomasking.
AB  - A major challenge in mapping health data is protecting patient privacy while
      maintaining the spatial resolution necessary for spatial surveillance and
      outbreak identification. A new adaptive geomasking technique, referred to as the
      donut method, extends current methods of random displacement by ensuring a user
      defined minimum level of geoprivacy. In donut method geomasking, each geocoded
      address is relocated in a random direction by at least a minimum distance, but
      less than a maximum distance. The authors compared the donut method with current
      methods of random perturbation and aggregation regarding measures of privacy
      protection and cluster detection performance by masking multiple disease field
      simulations under a range of parameters. Both the donut method and random
      perturbation performed better than aggregation in cluster detection measures. The
      performance of the donut method in geoprivacy measures was at least 42.7% higher
      and in cluster detection measures was less than 4.8% lower than that of random
      perturbation. Results show that the donut method provides a consistently higher
      level of privacy protection with a minimal decrease in cluster detection
      performance, especially in areas where the risk to individual geoprivacy is
      greatest.

PMID- 20817786
TI  - Incidence densities in a competing events analysis.
AB  - Epidemiologists often study the incidence density (ID; also known as incidence
      rate), which is the number of observed events divided by population-time at risk.
      Its computational simplicity makes it attractive in applications, but a common
      concern is that the ID is misleading if the underlying hazard is not constant in
      time. Another difficulty arises if competing events are present, which seems to
      have attracted less attention in the literature. However, there are situations in
      which the presence of competing events obscures the analysis more than
      nonconstant hazards do. The authors illustrate such a situation using data on
      infectious complications in patients receiving stem cell transplants, showing
      that a certain transplant type reduces the infection ID but eventually increases
      the cumulative infection probability because of its effect on the competing
      event. The authors investigate the extent to which IDs allow for a reasonable
      analysis of competing events. They suggest a simple multistate-type graphic based
      on IDs, which immediately displays the competing event situation. The authors
      also suggest a more formal summary analysis in terms of a best approximating
      effect on the cumulative event probability, considering another data example of
      US women infected with human immunodeficiency virus. Competing events and even
      more complex event patterns may be adequately addressed with the suggested
      methodology.

PMID- 20817787
TI  - Group I p21-activated kinases regulate thyroid cancer cell migration and are
      overexpressed and activated in thyroid cancer invasion.
AB  - p21-activated kinases (PAKs) are a family of serine/threonine kinases that
      regulate cytoskeletal dynamics and cell motility. PAKs are subdivided into group
      I (PAKs 1-3) and group II (PAKs 4-6) on the basis of structural and functional
      characteristics. Based on prior gene expression data that predicted enhanced PAK
      signaling in the invasive fronts of aggressive papillary thyroid cancers (PTCs),
      we hypothesized that PAKs functionally regulate thyroid cancer cell motility and
      are activated in PTC invasive fronts. We examined PAK isoform expression in six
      human thyroid cancer cell lines (BCPAP, KTC1, TPC1, FTC133, C643, and SW1746) by
      quantitative reverse transcription-PCR and western blot. All cell lines expressed
      PAKs 1-4 and PAK6 mRNA and PAKs 1-4 protein; PAK6 protein was variably expressed.
      Samples from normal and malignant thyroid tissues also expressed PAKs 1-4 and
      PAK6 mRNA; transfection with the group I (PAKs 1-3) PAK-specific p21 inhibitory
      domain molecular inhibitor reduced transwell filter migration by ~50% without
      altering viability in all cell lines (P<0.05). BCPAP and FTC133 cells were
      transfected with PAK1, PAK2, or PAK3-specific small interfering RNA (siRNA); only
      PAK1 siRNA reduced migration significantly for both cell lines.
      Immunohistochemical analysis of seven invasive PTCs demonstrated an increase in
      PAK1 and pPAK immunoactivity in the invasive fronts versus the tumor center. In
      conclusion, PAK isoforms are expressed in human thyroid tissues and cell lines.
      PAK1 regulates thyroid cancer cell motility, and PAK1 and pPAK levels are
      increased in PTC invasive fronts. These data implicate PAKs as regulators of
      thyroid cancer invasion.

PMID- 20817788
TI  - Mammalian target of rapamycin signaling activation patterns in neuroendocrine
      tumors of the lung.
AB  - Among alternative therapeutic strategies in clinically aggressive neuroendocrine
      tumors (NETs) of the lung, promising results have been obtained in experimental
      clinical trials with mammalian target of rapamycin (mTOR) inhibitors, though in
      the absence of a proven mTOR signaling activation status. This study analyzed the
      expression of phosphorylated mTOR (p-mTOR) and its major targets, the ribosomal
      p70S6-kinase (S6K) and the eukaryotic initiation factor 4E-binding protein 1
      (4EBP1) in a large series of 218 surgically resected, malignant lung NETs,
      including 24 metastasizing typical carcinoids, 73 atypical carcinoids, 60 large
      cell neuroendocrine carcinomas (LCNECs), and 61 small cell carcinomas (SCLCs). By
      immunohistochemistry, low-to-intermediate-grade tumors as compared with high
      grade tumors showed higher levels of p-mTOR and phosphorylated S6K (p-S6K)
      (P<0.001), at variance with phosphorylated 4EBP1 (p-4EBP1), which was mainly
      expressed in LCNECs and SCLCs (P<0.001). The activated status of mTOR pathway was
      proved by the strong correlation of p-mTOR with p-S6K and somatostatin
      receptor(s). Western blot analysis of NET tumor samples confirmed such findings,
      and differential sensitivity to mTOR inhibition according to mTOR pathway
      activation characteristics was determined in two lung carcinoid cell lines in
      vitro. None of the investigated molecules had an impact on survival. However, in
      low-grade tumors, low p-mTOR expression correlated with lymph node metastases
      (P=0.016), recurrent disease, and survival (P=0.005). In conclusion, these data
      demonstrate a differential mTOR activation status in the spectrum of pulmonary
      NETs, possibly suggesting that mTOR pathway profiling might play a predictive
      role in candidate patients for mTOR-targeted therapies.

PMID- 20817789
TI  - The orphan nuclear receptor LRH-1 promotes breast cancer motility and invasion.
AB  - The orphan nuclear receptor liver receptor homologue-1 (LRH-1) has roles in the
      development, cholesterol and bile acid homeostasis, and steroidogenesis. It also
      enhances proliferation and cell cycle progression of cancer cells. In breast
      cancer, LRH-1 expression is associated with invasive breast cancer; positively
      correlates with ERalpha status and aromatase activity; and promotes oestrogen
      dependent cell proliferation. However, the mechanism of action of LRH-1 in breast
      cancer epithelial cells is still not clear. By silencing or over-expressing LRH-1
      in ER-positive MCF-7 and ER-negative MDA-MB-231 breast cancer cells, we have
      demonstrated that LRH-1 promotes motility and cell invasiveness. Similar effects
      were observed in the non-tumourigenic mammary epithelial cell line, MCF-10A.
      Remodelling of the actin cytoskeleton and E-cadherin cleavage was observed with
      LRH-1 over-expression, contributing to increased migratory and invasive
      properties. Additionally, in LRH-1 over-expressing cells, the truncation of the
      120 kDa E-cadherin to the inactive 97 kDa form was observed. These post
      translational modifications in E-cadherin may be associated with LRH-1-dependent
      changes to matrix metalloproteinase 9 expression. These findings suggest a new
      role of LRH-1 in promoting migration and invasion in breast cancer, independent
      of oestrogen sensitivity. Therefore, LRH-1 may represent a new target for breast
      cancer therapeutics.

PMID- 20817790
TI  - Family intervention to control type 2 diabetes: a controlled clinical trial.
AB  - PURPOSE: Chilean patients with type 2 diabetes mellitus (T2DM) have a low rate of
      blood sugar control. We studied the effectiveness of a culturally sensitive
      family oriented intervention designed to improve metabolic control in primary
      care patients with uncontrolled T2DM. METHODS: Patients with T2DM from three
      primary care clinics in Santiago, Chile were randomly selected for inclusion if
      they had a recent HbA1c >=7%, were between 18 and 70 years old and lived with a
      family member. Patients from one clinic received the family oriented
      intervention; patients from the other two (control) clinics received standard
      care. The intervention involved family members in care and included family
      counselling during clinic visits, family meetings and home visits. The primary
      outcome was HbA1c, measured at 6 and 12 months. RESULTS: A total of 243 patients
      were enrolled and 209 (86%) completed the study. The intervention was fully
      administered to only 34% of patients in the intervention clinic. The reduction in
      the HbA1c from baseline to 12 months was not significantly different between
      clinics. During the second 6-month period, when the intervention was more
      intensive, the patients in the intervention clinic significantly improved their
      HbA1c (P < 0.001) compared to the control patients. CONCLUSIONS: A family
      intervention for the control of T2DM was associated with a significant reduction
      in HbA1c when the intervention was provided. Incomplete implementation, low
      statistical power and potential confounding variables between groups could be
      some of the main factors that explain the lack of difference between clinics in
      the 12-month period.

PMID- 20817791
TI  - Referral recommendations for osteoarthritis of the knee incorporating patients'
      preferences.
AB  - BACKGROUND: GPs have to respond to conflicting policy developments. As gatekeeper
      they are supposed to manage the growing demand for specialist services and as
      patient advocate they should be responsive to patients' preferences. We used an
      innovative approach to develop a referral guideline for patients with chronic
      knee pain that explicitly incorporates patients' preferences. METHODS: A
      guideline development group of 12 members including patients, GPs, orthopaedic
      surgeons and other health care professionals used formal consensus development
      informed by systematic evidence reviews. They rated the appropriateness of
      referral for 108 case scenarios describing patients according to symptom
      severity, age, body mass, co-morbidity and referral preference. Appropriateness
      was expressed on scale from 1 ('strongly disagree') to 9 ('strongly agree').
      RESULTS: Ratings of referral appropriateness were strongly influenced by symptom
      severity and patients' referral preferences. The influence of other patient
      characteristics was small. There was consensus that patients with severe knee
      symptoms who want to be referred should be referred and that patient with
      moderate or mild symptoms and strong preference against referral should not be
      referred. Referral preference had a greater impact on the ratings of referral
      appropriateness when symptoms were moderate or severe than when symptoms were
      mild. CONCLUSIONS: Referral decisions for patients with osteoarthritis of the
      knee should only be guided by symptom severity and patients' referral
      preferences. The guideline development group seemed to have given priority to
      avoiding inefficient resource use in patients with mild symptoms and to
      respecting patient autonomy in patients with severe symptoms.

PMID- 20817792
TI  - The tragedy of the microarray anticommons.

PMID- 20817793
TI  - Cancer genomes.

PMID- 20817794
TI  - Atorvastatin increases 25-hydroxy vitamin D concentrations in patients with
      polycystic ovary syndrome.
AB  - BACKGROUND: It has been shown that many women with polycystic ovary syndrome
      (PCOS) are 25-hydroxyvitamin D (25OHD) insufficient. Both statin treatment and
      vitamin D supplementation have been shown to improve biochemical
      hyperandrogenemia, insulin resistance, and markers of inflammation in patients
      with PCOS, raising the possibility that some of the statin effects are mediated
      through vitamin D. METHODS: We conducted this randomized, double-blind placebo
      controlled study to assess the effect of atorvastatin on serum 25OHD
      concentrations in patients with PCOS. Forty medication-naive patients with PCOS
      were randomized to either atorvastatin 20 mg daily or placebo for 3 months. After
      completing the initial 3 months of atorvastatin or placebo, both groups of
      patients participated in a 3-month extension study with metformin 1500 mg daily.
      We measured changes in 25OHD concentrations by use of tandem mass spectrometry.
      RESULTS: Mean (SD) baseline 25OHD concentrations were comparable between the 2
      groups [45.9 (2.4) vs 44.8 (1.8) nmol/L; P = 0.7]. There was a significant
      increase in 25OHD concentrations with atorvastatin [45.9 (2.4) vs 60.8 (3.5)
      nmol/L] compared with placebo [44.8 (1.8) vs 41.8 (3.2) nmol/L; P = 0.02]. Three
      month treatment with metformin maintained the improvement of 25OHD with
      atorvastatin compared to baseline [45.9 (2.4) vs 61.8 (3.5), P <= 0.01). There
      were no significant changes in 25OHD concentrations in the placebo group after 12
      weeks of metformin. CONCLUSIONS: Among patients with polycystic ovary syndrome,
      12 weeks of atorvastatin led to a clinically significant rise in 25OHD
      concentrations. This may represent a beneficial pleiotropic effect of statins on
      25OHD concentrations.

PMID- 20817795
TI  - Enhancement of the diversity of polyoxins by a thymine-7-hydroxylase homolog
      outside the polyoxin biosynthesis gene cluster.
AB  - Polyoxins consist of 14 structurally variable components which differentiate at
      three branch sites of the carbon skeleton. Open reading frame (ORF) SAV_4805 of
      Streptomyces avermitilis, showing similarity to thymine-7-hydroxylase, was proved
      to enhance the diversity of polyoxins at the C-5 site of the 1-(5'-amino-5'-deoxy
      beta-d-allofuranuronosyl) pyrimidine moiety.

PMID- 20817796
TI  - Development of amplified fragment length polymorphism-derived functional strain
      specific markers to assess the persistence of 10 bacterial strains in soil
      microcosms.
AB  - To augment the information on commercial microbial products, we investigated the
      persistence patterns of high-priority bacterial strains from the Canadian
      Domestic Substance List (DSL). Specific DNA markers for each of the 10 DSL
      bacterial strains were developed using the amplified fragment length polymorphism
      (AFLP) technique, and the fates of DSL strains introduced in soil were assessed
      by real-time quantitative PCR (qPCR). The results indicated that all DNA markers
      had high specificity at the functional strain level and that detection of the
      target microorganisms was sensitive at a detection limitation range from 1.3 *
      102 to 3.25 * 105 CFU/g of dry soil. The results indicated that all introduced
      strains showed a trend toward a declining persistence in soil and could be
      categorized into three pattern types. The first type was long-term persistence
      exemplified by Pseudomonas stutzeri (ATCC 17587) and Pseudomonas denitrificans
      (ATCC 13867) strains. In the second pattern, represented by Bacillus subtilis
      (ATCC 6051) and Escherichia hermannii (ATCC 700368), the inoculated strain
      populations dropped dramatically below the detection threshold after 10 to 21
      days, while in the third pattern there was a gradual decrease, with the
      population falling below the detectable level within the 180-day incubation
      period. These patterns indicate a selection effect of a microbial community
      related to the ecological function of microbial strains introduced in soil. As a
      key finding, the DSL strains can be quantitatively tracked in soil with high
      sensitivity and specificity at the functional strain level. This provides the
      basic evidence for further risk assessment of the priority DSL strains.

PMID- 20817797
TI  - Label-free bacterial imaging with deep-UV-laser-induced native fluorescence.
AB  - We introduce a near-real-time optical imaging method that works via the detection
      of the intrinsic fluorescence of life forms upon excitation by deep-UV (DUV)
      illumination. A DUV (<250-nm) source enables the detection of microbes in their
      native state on natural materials, avoiding background autofluorescence and
      without the need for fluorescent dyes or tags. We demonstrate that DUV-laser
      induced native fluorescence can detect bacteria on opaque surfaces at spatial
      scales ranging from tens of centimeters to micrometers and from communities to
      single cells. Given exposure times of 100 MUs and low excitation intensities,
      this technique enables rapid imaging of bacterial communities and cells without
      irreversible sample alteration or destruction. We also demonstrate the first
      noninvasive detection of bacteria on in situ-incubated environmental experimental
      samples from the deep ocean (Lo'ihi Seamount), showing the use of DUV native
      fluorescence for in situ detection in the deep biosphere and other nutrient
      limited environments.

PMID- 20817798
TI  - Accuracy, precision, and method detection limits of quantitative PCR for airborne
      bacteria and fungi.
AB  - Real-time quantitative PCR (qPCR) for rapid and specific enumeration of microbial
      agents is finding increased use in aerosol science. The goal of this study was to
      determine qPCR accuracy, precision, and method detection limits (MDLs) within the
      context of indoor and ambient aerosol samples. Escherichia coli and Bacillus
      atrophaeus vegetative bacterial cells and Aspergillus fumigatus fungal spores
      loaded onto aerosol filters were considered. Efficiencies associated with
      recovery of DNA from aerosol filters were low, and excluding these efficiencies
      in quantitative analysis led to underestimating the true aerosol concentration by
      10 to 24 times. Precision near detection limits ranged from a 28% to 79%
      coefficient of variation (COV) for the three test organisms, and the majority of
      this variation was due to instrument repeatability. Depending on the organism and
      sampling filter material, precision results suggest that qPCR is useful for
      determining dissimilarity between two samples only if the true differences are
      greater than 1.3 to 3.2 times (95% confidence level at n = 7 replicates). For
      MDLs, qPCR was able to produce a positive response with 99% confidence from the
      DNA of five B. atrophaeus cells and less than one A. fumigatus spore. Overall MDL
      values that included sample processing efficiencies ranged from 2,000 to 3,000 B.
      atrophaeus cells per filter and 10 to 25 A. fumigatus spores per filter. Applying
      the concepts of accuracy, precision, and MDL to qPCR aerosol measurements
      demonstrates that sample processing efficiencies must be accounted for in order
      to accurately estimate bioaerosol exposure, provides guidance on the necessary
      statistical rigor required to understand significant differences among separate
      aerosol samples, and prevents undetected (i.e., nonquantifiable) values for true
      aerosol concentrations that may be significant.

PMID- 20817799
TI  - Improved method for bacterial cell capture after flow cytometry cell sorting.
AB  - Fixed cells with different nucleic acid contents and scatter properties (low
      nucleic acid [LNA], high nucleic acid 1 [HNA1], and HNA2) were sorted by flow
      cytometry (FCM). For each sort, 10,000 cells were efficiently captured on poly-l
      lysine-coated microplates, resulting in efficient and reproducible PCR
      amplification.

PMID- 20817800
TI  - Clonal species Trichoderma parareesei sp. nov. likely resembles the ancestor of
      the cellulase producer Hypocrea jecorina/T. reesei.
AB  - We have previously reported that the prominent industrial enzyme producer
      Trichoderma reesei (teleomorph Hypocrea jecorina; Hypocreales, Ascomycota,
      Dikarya) has a genetically isolated, sympatric sister species devoid of sexual
      reproduction and which is constituted by the majority of anamorphic strains
      previously attributed to H. jecorina/T. reesei. In this paper we present the
      formal taxonomic description of this new species, T. parareesei, complemented by
      multivariate phenotype profiling and molecular evolutionary examination. A
      phylogenetic analysis of relatively conserved loci, such as coding fragments of
      the RNA polymerase B subunit II (rpb2) and GH18 chitinase (chi18-5), showed that
      T. parareesei is genetically invariable and likely resembles the ancestor which
      gave raise to H. jecorina. This and the fact that at least one mating type gene
      of T. parareesei has previously been found to be essentially altered compared to
      the sequence of H. jecorina/T. reesei indicate that divergence probably occurred
      due to the impaired functionality of the mating system in the hypothetical
      ancestor of both species. In contrast, we show that the sexually reproducing and
      correspondingly more polymorphic H. jecorina/T. reesei is essentially
      evolutionarily derived. Phenotype microarray analyses performed at seven
      temperature regimens support our previous speculations that T. parareesei
      possesses a relatively high opportunistic potential, which probably ensured the
      survival of this species in ancient and sustainable environment such as tropical
      forests.

PMID- 20817801
TI  - Stimulation of methane generation from nonproductive coal by addition of
      nutrients or a microbial consortium.
AB  - Biogenic formation of methane from coal is of great interest as an underexploited
      source of clean energy. The goal of some coal bed producers is to extend coal bed
      methane productivity and to utilize hydrocarbon wastes such as coal slurry to
      generate new methane. However, the process and factors controlling the process,
      and thus ways to stimulate it, are poorly understood. Subbituminous coal from a
      nonproductive well in south Texas was stimulated to produce methane in microcosms
      when the native population was supplemented with nutrients (biostimulation) or
      when nutrients and a consortium of bacteria and methanogens enriched from wetland
      sediment were added (bioaugmentation). The native population enriched by nutrient
      addition included Pseudomonas spp., Veillonellaceae, and Methanosarcina barkeri.
      The bioaugmented microcosm generated methane more rapidly and to a higher
      concentration than the biostimulated microcosm. Dissolved organics, including
      long-chain fatty acids, single-ring aromatics, and long-chain alkanes accumulated
      in the first 39 days of the bioaugmented microcosm and were then degraded,
      accompanied by generation of methane. The bioaugmented microcosm was dominated by
      Geobacter sp., and most of the methane generation was associated with growth of
      Methanosaeta concilii. The ability of the bioaugmentation culture to produce
      methane from coal intermediates was confirmed in incubations of culture with
      representative organic compounds. This study indicates that methane production
      could be stimulated at the nonproductive field site and that low microbial
      biomass may be limiting in situ methane generation. In addition, the microcosm
      study suggests that the pathway for generating methane from coal involves complex
      microbial partnerships.

PMID- 20817802
TI  - Relationships between environmental factors and pathogenic Vibrios in the
      Northern Gulf of Mexico.
AB  - Although autochthonous vibrio densities are known to be influenced by water
      temperature and salinity, little is understood about other environmental factors
      associated with their abundance and distribution. Densities of culturable Vibrio
      vulnificus containing vvh (V. vulnificus hemolysin gene) and V. parahaemolyticus
      containing tlh (thermolabile hemolysin gene, ubiquitous in V. parahaemolyticus),
      tdh (thermostable direct hemolysin gene, V. parahaemolyticus pathogenicity
      factor), and trh (tdh-related hemolysin gene, V. parahaemolyticus pathogenicity
      factor) were measured in coastal waters of Mississippi and Alabama. Over a 19
      month sampling period, vibrio densities in water, oysters, and sediment varied
      significantly with sea surface temperature (SST). On average, tdh-to-tlh ratios
      were significantly higher than trh-to-tlh ratios in water and oysters but not in
      sediment. Although tlh densities were lower than vvh densities in water and in
      oysters, the opposite was true in sediment. Regression analysis indicated that
      SST had a significant association with vvh and tlh densities in water and
      oysters, while salinity was significantly related to vibrio densities in the
      water column. Chlorophyll a levels in the water were correlated significantly
      with vvh in sediment and oysters and with pathogenic V. parahaemolyticus (tdh and
      trh) in the water column. Furthermore, turbidity was a significant predictor of
      V. parahaemolyticus density in all sample types (water, oyster, and sediment),
      and its role in predicting the risk of V. parahaemolyticus illness may be more
      important than previously realized. This study identified (i) culturable vibrios
      in winter sediment samples, (ii) niche-based differences in the abundance of
      vibrios, and (iii) predictive signatures resulting from correlations between
      environmental parameters and vibrio densities.

PMID- 20817803
TI  - Detection of Mycobacterium avium subsp. paratuberculosis in drinking water and
      biofilms by quantitative PCR.
AB  - It has been suggested that Mycobacterium avium subspecies paratuberculosis has a
      role in Crohn's disease. The organism may be acquired but is difficult to culture
      from the environment. We describe a quantitative PCR (qPCR) method to detect M.
      avium subsp. paratuberculosis in drinking water and the results of its
      application to drinking water and faucet biofilm samples collected in the United
      States.

PMID- 20817804
TI  - Halophiles 2010: life in saline environments.

PMID- 20817805
TI  - Recent emergence of clonal group O25b:K1:H4-B2-ST131 ibeA strains among
      Escherichia coli poultry isolates, including CTX-M-9-producing strains, and
      comparison with clinical human isolates.
AB  - To discern the possible spread of the Escherichia coli O25b:H4-ST131 clonal group
      in poultry and the zoonotic potential of avian strains, we made a retrospective
      search of our strain collection and compared the findings for those strains with
      the findings for current strains. Thus, we have characterized a collection of 19
      avian O25b:H4-ST131 E. coli strains isolated from 1995 to 2010 which,
      interestingly, harbored the ibeA gene. Using this virulence gene as a criterion
      for selection, we compared those 19 avian strains with 33 human O25b:H4-ST131
      ibeA-positive E. coli strains obtained from patients with extraintestinal
      infections (1993 to 2009). All 52 O25b:H4-ST131 ibeA-positive E. coli strains
      shared the fimH, kpsMII, malX, and usp genes but showed statistically significant
      differences in nine virulence factors, namely, papGIII, cdtB, sat, and kpsMII K5,
      which were associated with human strains, and iroN, kpsMII K1, cvaC, iss, and
      tsh, which were associated with strains of avian origin. The XbaI
      macrorestriction profiles of the 52 E. coli O25b:H4-ST131 ibeA-positive strains
      revealed 11 clusters (clusters I to XI) of >85% similarity, with four clusters
      including strains of human and avian origin. Cluster VII (90.9% similarity)
      grouped 10 strains (7 avian and 3 human strains) that mostly produced CTX-M-9 and
      that also shared the same virulence profile. Finally, we compared the
      macrorestriction profiles of the 12 CTX-M-9-producing O25b:H4-ST131 ibeA strains
      (7 avian and 5 human strains) identified among the 52 strains with those of 15
      human O25b:H4-ST131 CTX-M-14-, CTX-M-15-, and CTX-M-32-producing strains that
      proved to be negative for ibeA and showed that they clearly differed in the level
      of similarity from the CTX-M-9-producing strains. In conclusion, E. coli clonal
      group O25b:H4-ST131 ibeA has recently emerged among avian isolates with the new
      acquisition of the K1 capsule antigen and includes CTX-M-9-producing strains.
      This clonal group represents a real zoonotic risk that has crossed the barrier
      between human and avian hosts.

PMID- 20817806
TI  - Selection and characterization of a multivalent Salmonella phage and its
      production in a nonpathogenic Escherichia coli strain.
AB  - We report the selection and amplification of the broad-host-range Salmonella
      phage phi PVP-SE1 in an alternative nonpathogenic host. The lytic spectrum and
      the phage DNA restriction profile were not modified upon replication in
      Escherichia coli Bl21, suggesting the possibility of producing this phage in a
      nonpathogenic host, contributing to the safety and easier approval of a product
      based on this Salmonella biocontrol agent.

PMID- 20817807
TI  - Inclusion of dried or wet distillers' grains at different levels in diets of
      feedlot cattle affects fecal shedding of Escherichia coli O157:H7.
AB  - Our objectives were to evaluate the prevalence of Escherichia coli O157:H7 in
      cattle fed diets supplemented with 20 or 40% dried distillers' grains (DG) (DDG)
      or wet DG (WDG) and assess whether removing DG from diets before slaughter
      affected fecal shedding of E. coli O157:H7. Eight hundred forty steers were
      allocated to 70 pens (12 steers/pen). Treatments were no DG (control), 20% DDG or
      WDG, and 40% DDG or WDG, and each was replicated in 14 pens. In phase 1, eight
      floor fecal samples were collected from each pen every 2 weeks for 12 weeks for
      isolation of E. coli O157:H7 and detection of high shedders. In phase 2, half of
      the pens with DG were transitioned to the no-DG control diet, and pen floor fecal
      samples were collected weekly from all pens for 4 weeks. During phase 1,
      prevalence of E. coli O157:H7 was 20.8% and 3.2% for high shedders. The form of
      DG had no significant effect on fecal E. coli O157:H7 shedding. The prevalence
      levels of E. coli O157:H7 and the numbers of high shedders were not different
      between diets with 0 or 20% DG; however, cattle fed 40% DG had a higher
      prevalence and more high shedders than cattle fed 0 or 20% DG (P <= 0.05). During
      phase 2, overall and high-shedder prevalence estimates were 3.3% and <0.1%,
      respectively, and there were no differences between those for different DG forms
      and inclusion levels or when DG was removed from diets. The form of DG had no
      impact on E. coli O157:H7; however, fecal shedding was associated with the DG
      inclusion level.

PMID- 20817808
TI  - Biological approach to modeling of Staphylococcus aureus high-hydrostatic
      pressure inactivation kinetics.
AB  - Graphs for survival under high hydrostatic pressure (450 MPa; 25 degrees C;
      citrate-phosphate buffer, pH 7.0) of stationary-growth-phase cells of eight
      Staphylococcus aureus strains were found to be nonlinear. The strains could be
      classified into two groups on the basis of the shoulder length. Some of them
      showed long shoulders of up to 20 min at 450 MPa, while others had shoulders of
      <3.5 min. All strains showed tails. No significant differences in the
      inactivation rate were found during the log-linear death phase among the eight
      strains. The entry into stationary growth phase resulted both in an increase in
      shoulder length and in a decrease in the inactivation rate. However, whereas
      shoulder length proved to depend on sigma B factor activity, the inactivation
      rate did not. Recovery in anaerobiosis decreased the inactivation rate but did
      not affect the shoulder length. Addition of the minimum noninhibitory
      concentration of sodium chloride to the recovery medium resulted in a decrease in
      shoulder length and in an increase in the inactivation rate for stationary-growth
      phase cells. In the tail region, up to 90% of the population remained sensitive
      to sodium chloride.

PMID- 20817809
TI  - Temperature-dependent requirement for catalase in aerobic growth of Listeria
      monocytogenes F2365.
AB  - Listeria monocytogenes is a Gram-positive, psychrotrophic, facultative
      intracellular food-borne pathogen responsible for severe illness (listeriosis).
      The bacteria can grow in a wide range of temperatures (1 to 45 degrees C), and
      low-temperature growth contributes to the food safety hazards associated with
      contamination of ready-to-eat foods with this pathogen. To assess the impact of
      oxidative stress responses on the ability of L. monocytogenes to grow at low
      temperatures and to tolerate repeated freeze-thaw stress (cryotolerance), we
      generated and characterized a catalase-deficient mutant of L. monocytogenes F2365
      harboring a mariner-based transposon insertion in the catalase gene (kat). When
      grown aerobically on blood-free solid medium, the kat mutant exhibited impaired
      growth, with the extent of impairment increasing with decreasing temperature, and
      no growth was detected at 4 degrees C. Aerobic growth in liquid was impaired at 4
      degrees C, especially under aeration, but not at higher temperatures (10, 25, or
      37 degrees C). Genetic complementation of the mutant with the intact kat restored
      normal growth, confirming that inactivation of this gene was responsible for the
      growth impairment. In spite of the expected impact of oxidative stress responses
      on cryotolerance, cryotolerance of the kat mutant was not affected.

PMID- 20817810
TI  - Contribution of chitinases to Listeria monocytogenes pathogenesis.
AB  - Listeria monocytogenes secretes two chitinases and one chitin binding protein.
      Mutants lacking chiA, chiB, or lmo2467 exhibited normal growth in cultured cells
      but were defective for growth in the livers and spleens of mice. Mammals lack
      chitin; thus, L. monocytogenes may have adapted chitinases to recognize
      alternative substrates to enhance pathogenesis.

PMID- 20817811
TI  - Towards enhanced galactose utilization by Lactococcus lactis.
AB  - Accumulation of galactose in dairy products due to partial lactose fermentation
      by lactic acid bacteria yields poor-quality products and precludes their
      consumption by individuals suffering from galactosemia. This study aimed at
      extending our knowledge of galactose metabolism in Lactococcus lactis, with the
      final goal of tailoring strains for enhanced galactose consumption. We used
      directed genetically engineered strains to examine galactose utilization in
      strain NZ9000 via the chromosomal Leloir pathway (gal genes) or the plasmid
      encoded tagatose 6-phosphate (Tag6P) pathway (lac genes). Galactokinase (GalK),
      but not galactose permease (GalP), is essential for growth on galactose. This
      finding led to the discovery of an alternative route, comprising a galactose
      phosphotransferase system (PTS) and a phosphatase, for galactose dissimilation in
      NZ9000. Introduction of the Tag6P pathway in a galPMK mutant restored the ability
      to metabolize galactose but did not sustain growth on this sugar. The latter
      strain was used to prove that lacFE, encoding the lactose PTS, is necessary for
      galactose metabolism, thus implicating this transporter in galactose uptake. Both
      PTS transporters have a low affinity for galactose, while GalP displays a high
      affinity for the sugar. Furthermore, the GalP/Leloir route supported the highest
      galactose consumption rate. To further increase this rate, we overexpressed
      galPMKT, but this led to a substantial accumulation of alpha-galactose 1
      phosphate and alpha-glucose 1-phosphate, pointing to a bottleneck at the level of
      alpha-phosphoglucomutase. Overexpression of a gene encoding alpha
      phosphoglucomutase alone or in combination with gal genes yielded strains with
      galactose consumption rates enhanced up to 50% relative to that of NZ9000.
      Approaches to further improve galactose metabolism are discussed.

PMID- 20817812
TI  - Analysis of the Lactobacillus metabolic pathway.
AB  - We performed analyses of the phenotypic and genotypic relationships focusing on
      biosyntheses of amino acids, purine/pyrimidines, and cofactors in three
      Lactobacillus strains. We found that Lactobacillus fermentum IFO 3956 perhaps
      synthesized para-aminobenzoate (PABA), an intermediate of folic acid
      biosynthesis, by an alternative pathway.

PMID- 20817813
TI  - Young Kuwaitis' views of the acceptability of physician-assisted suicide.
AB  - AIM: To study the views of people in a largely Muslim country, Kuwait, of the
      acceptability of a life-ending action such as physician-assisted suicide (PAS).
      METHOD: 330 Kuwaiti university students judged the acceptability of PAS in 36
      scenarios composed of all combinations of four factors: the patient's age (35, 60
      or 85 years); the level of incurability of the illness (completely incurable vs
      extremely difficult to cure); the type of suffering (extreme physical pain or
      complete dependence) and the extent to which the patient requests a life-ending
      procedure, euthanasia or PAS (no request, some form of request, repeated
      requests). In all scenarios, the patients were women who were receiving the best
      possible care. The ratings were subjected to cluster analysis and analyses of
      variance. RESULTS: Five clusters were found. For 44%, PAS was always very
      unacceptable, no matter what the circumstances. For 23%, it was unacceptable, but
      less so if the patient was older or requested it repeatedly. For 16%, it was
      unacceptable if the patient was young but was acceptable if the patient was
      elderly. For 5%, it was unacceptable if the patient had extreme pain but was
      acceptable if completely dependent. For 11%, it was unacceptable if the patient
      did not request it but acceptable if she did. CONCLUSION: The majority of the
      Kuwaiti university students opposed PAS either categorically or with a slight
      variation according to circumstances. Nonetheless, a minority approved of PAS in
      some cases, particularly when the patient was elderly.

PMID- 20817814
TI  - A written consent five centuries ago.
AB  - The term informed consent does not have long historical roots. Until recent
      centuries, healthcare professionals were not held responsible for providing
      information to patients. The author reports a written consent from Anatolia dated
      almost five centuries ago. The contract was signed in 1539 in Gaziantep, Turkey
      (formerly known as Aintab, Ottoman Empire). The document, of course, differs from
      modern counterparts. It lacks details of interventions. The author believes this
      to be the first written consent in medical history. Further investigations of
      court registers should be made to ascertain the earliest date of their
      appearance.

PMID- 20817815
TI  - Pulling the heartstrings, arguing the case: a narrative response to the issue of
      moral agency in moral distress.
AB  - In this paper it is argued that moral distress is an emotional response to an
      ethical dilemma, and that to date, the literature has largely failed to address
      the fundamental questions that need to be answered in response to this emotional
      response. Firstly, does moral distress accurately identify a wrong being done to
      patients? Secondly, if it does, can nurses carry out this 'wrong doing', but not
      be responsible for the consequences of their actions? A narrative that reflects
      the emotional nature of moral distress is presented, with the aim of providing
      some answers to these questions.

PMID- 20817816
TI  - Should patients with self-inflicted illness receive lower priority in access to
      healthcare resources? Mapping out the debate.
AB  - The distribution of scarce healthcare resources is an increasingly important
      issue due to factors such as expensive 'high tech' medicine, longer life
      expectancies and the rising prevalence of chronic illness. Furthermore, in the
      current healthcare context lifestyle-related factors such as high blood pressure,
      tobacco use and obesity are believed to contribute significantly to the global
      burden of disease. As such, this paper focuses on an ongoing debate in the
      academic literature regarding the role of responsibility for illness in
      healthcare resource allocation: should patients with self-caused illness receive
      lower priority in access to healthcare resources? This paper critically describes
      the lower priority debate's 12 key arguments and maps out their relationships.
      This analysis reveals that most arguments have been refuted and that the debate
      has stalled and remains unresolved. In conclusion, we suggest progression could
      be achieved by inviting multidisciplinary input from a range of stakeholders for
      the development of evidence-based critical evaluations of existing arguments and
      the development of novel arguments, including the outstanding rebuttals.

PMID- 20817818
TI  - A patient and relative centred evaluation of treatment escalation plans: a
      replacement for the do-not-resuscitate process.
AB  - The Treatment Escalation Plan (TEP) was introduced into our trust in an attempt
      to improve patient involvement and experience of their treatment in hospital and
      to embrace and clarify a wider remit of treatment options than the Do Not
      Resuscitate (DNR) order currently offers. Our experience suggests that the
      patient and family are rarely engaged in DNR discussions. This is acutely
      relevant considering that the Mental Capacity Act (MCA) now obliges these
      discussions to take place. The TEP is a form that the doctor completes, ideally
      with the competent patient or close relative, documenting what treatment options
      would be appropriate if that patient were to become acutely unwell. Ventilation
      of the lungs, cardiac resuscitation, renal replacement therapy, intravenous
      fluids and antibiotics are all discussed. The study evaluated patient and
      relative experiences with the TEP. 55 patients or their relatives were
      interviewed regarding their experience of the TEP and thoughts regarding the
      process. 96% of patients and relatives evaluated thought that the TEP was a good
      idea. Free text comments were all positive and only 34% of patients claimed to
      feel anxious when completing the form. Following this study, the TEP has been
      expanded hospital wide and into the community within our trust. Discussions are
      currently taking place in hospitals within our region to introduce the TEP form
      into other local trusts.

PMID- 20817819
TI  - The problem of 'thick in status, thin in content' in Beauchamp and Childress'
      principlism.
AB  - For many, Thomas Beauchamp and James Childress have elaborated moral reasoning by
      using the four principles whereby all substantive problems of medical ethics (and
      of ethics more generally) can be properly analysed and cogent philosophical
      solutions for the problems can be found. It seems that their 'principlism' gets
      updated, with better features being added during the course of the six editions
      of Principles of Biomedical Ethics. Nonetheless, Beauchamp and Childress seem to
      have been losing their way when it comes to the common-morality justification,
      which is the epistemological (and perhaps metaphysical) backbone of their method,
      and this is shown more vividly in their most recent (2009) edition of Principles
      of Biomedical Ethics. The author points out what he calls the problem of 'thick
      in status, thin in content' in principlism. The problem exists because
      principlism cannot adequately explain how the prescriptive sense of common
      morality it supports is consistent with the existence of what Beauchamp and
      Childress call the 'legitimate moral diversity in the world'. Because of this
      problem, first, the practical end that principlism allegedly accomplishes (ie,
      providing practical moral guidelines in a relatively 'thick' content, based on
      common morality) is frustrated, and, second, principlism makes itself the method
      of common morality de jure and of moral pluralism de facto.

PMID- 20817820
TI  - The potential impact of an opt-out system for organ donation in the UK.
AB  - The recent report of the UK government's Organ Donation Taskforce is in favour of
      continuing with the current organ donation system rather than changing to an opt
      out system where people are assumed to be willing to donate. How did it reach
      this decision and is it correct?

PMID- 20817821
TI  - Teaching practical wisdom in medicine through clinical judgement, goals of care,
      and ethical reasoning.
AB  - Clinical decision making is a challenging task that requires practical wisdom-the
      practised ability to help patients choose wisely among available diagnostic and
      treatment options. But practical wisdom is not a concept one typically hears
      mentioned in medical training and practice. Instead, emphasis is placed on
      clinical judgement. The author draws from Aristotle and Aquinas to describe the
      virtue of practical wisdom and compare it with clinical judgement. From this
      comparison, the author suggests that a more complete understanding of clinical
      judgement requires its explicit integration with goals of care and ethical
      values. Although clinicians may be justified in assuming that goals of care and
      ethical values are implicit in routine decision making, it remains important for
      training purposes to encourage habits of clinical judgement that are consciously
      goal-directed and ethically informed. By connecting clinical judgement to
      patients' goals and values, clinical decisions are more likely to stay focused on
      the particular interests of individual patients. To cultivate wise clinical
      judgement among trainees, educational efforts should aim at the integration of
      clinical judgement, communication with patients about goals of care, and ethical
      reasoning. But ultimately, training in wise clinical judgement will take years of
      practice in the company of experienced clinicians who are able to demonstrate
      practical wisdom by example. By helping trainees develop clinical judgement that
      incorporates patients' goals of care and ethical reasoning, we may help lessen
      the risk that 'clinical judgement' will merely express 'the clinician's
      judgement.'

PMID- 20817822
TI  - The top ten list of challenges for radiation protection dosimetry in 2011.

PMID- 20817823
TI  - Increasing social engagement among lonely individuals: the role of acceptance
      cues and promotion motivations.
AB  - Lonely individuals typically fear negative evaluation and engage in overly
      cautious social behaviors that perpetuate their social isolation. Recent research
      has found analogous security-oriented (i.e., prevention-focused) responses
      following experiences highlighting concerns with social loss but differing growth
      oriented (i.e., promotion-focused ) responses, such as attempts at social
      engagement, following experiences highlighting concerns with social gain. The
      present studies thus investigated whether fostering a promotion focus among
      lonely individuals through subtle primes of acceptance could reduce their self
      protective social avoidance. This hypothesis was supported across four studies in
      which the links between primed acceptance and promotion-focused motivations were
      first established, and the impact of such primes on lonely individuals' social
      thoughts, intentions, and behaviors were then tested. Implications of observed
      differences between effects of acceptance primes on lonely versus nonlonely
      individuals are discussed in terms of deficits versus satiation with feelings of
      belonging.

PMID- 20817824
TI  - Real-time fluorescent resonance energy transfer analysis to monitor drug
      resistance in chronic myelogenous leukemia.
AB  - Despite the initial effectiveness of oncogene-directed cancer therapeutics,
      acquired drug resistance remains the ultimate "Achilles' heel" for long-term
      durable remission in cancer patients. Acquisition of drug resistance is not more
      evident elsewhere than in the use of tyrosine kinase inhibitors, imatinib and
      dasatinib, for patients with chronic myelogenous leukemia. Hence, even though
      imatinib initially produces remission in the chronic phase, ultimately these
      therapeutics fail via the emergence of drug resistance, in which chronic
      myelogenous leukemia could inevitably progress to a terminal blast phase
      culminating in fatal outcome. Technically, it is challenging to predict the onset
      of drug resistance in a small number of oncogene-transformed cells, making the
      decision of when and how to employ second-generation tyrosine kinase inhibitors,
      or employ novel compounds that would be of benefit in treating drug-resistant Bcr
      Abl mutants mainly retrospective. Here, we characterize a rapid and sensitive
      real-time fluorescent resonance energy transfer-based assay that is able to
      detect the in vivo activity of Bcr-Abl and its inhibition by small molecule
      compounds. Due to its real-time and in vivo nature, such an approach has the
      potential to monitor a drug-resistant phenotype, as well as to identify
      pharmaceutical agents that inhibit drug-resistant Bcr-Abl oncoproteins in vivo.

PMID- 20817825
TI  - SDF-1 axis and myocardial repair.

PMID- 20817826
TI  - Progressive chronic heart failure slows the recovery of microvascular O2
      pressures after contractions in the rat spinotrapezius muscle.
AB  - Chronic heart failure (CHF) induces muscle fiber-type specific alterations in
      skeletal muscle O(2) delivery and utilization during metabolic transitions. As a
      result, the recovery of microvascular Po(2) (Pmv(O(2))) is prolonged in slow
      twitch skeletal muscle but not fast-twitch skeletal muscle in rats with CHF. We
      tested the hypothesis that CHF slows Pmv(O(2)) recovery in rat skeletal muscle of
      a mixed fiber-type analogous to human locomotory muscles and that the degree of
      slowing correlates with central indexes of heart failure. Healthy control [n = 6,
      left ventricular end-diastolic pressure (LVEDP): 10 +/- 1 mmHg], moderate CHF (n
      = 6, LVEDP: 18 +/- 2 mmHg), and severe CHF (n = 4, LVEDP: 34 +/- 2 mmHg) female
      Sprague-Dawley rats had their right spinotrapezius muscles (41% type I, 7% type
      IIa, and 52% type IIb and d/x) exposed, and Pmv(O(2)) was measured via
      phosphorescence quenching during 180 s of recovery from 180 s of electrically
      induced twitch contractions (1 Hz, 4-6 V). CHF progressively slowed the mean
      response time (MRT; the time to reach 63% of the overall dynamic response) of
      Pmv(O(2)) recovery (MRT(off); control: 60.2 +/- 6.9, moderate CHF: 72.8 +/- 6.6,
      and severe CHF: 109.8 +/- 6.6 s, P < 0.05 for all). MRT(off) correlated
      positively with central hemodynamic (LVEDP: r = 0.76, P < 0.01) and morphological
      (right ventricle-to-body weight ratio: r = 0.74, P < 0.01; and lung weight-to
      body weight ratio: r = 0.79, P < 0.01) indexes of heart failure. The present
      investigation suggests that slowed Pmv(O(2)) kinetics during recovery in CHF
      constitutes a mechanistic link between impaired circulatory and metabolic
      recovery after contractions in CHF.

PMID- 20817827
TI  - Extracellular transsulfuration generates hydrogen sulfide from homocysteine and
      protects endothelium from redox stress.
AB  - Homocysteine, a cardiovascular and neurocognitive disease risk factor, is
      converted to hydrogen sulfide, a cardiovascular and neuronal protectant, through
      the transsulfuration pathway. Given the damaging effects of free homocysteine in
      the blood and the importance of blood homocysteine concentration as a
      prognosticator of disease, we tested the hypotheses that the blood itself
      regulates homocysteine-hydrogen sulfide metabolism through transsulfuration and
      that transsulfuration capacity and hydrogen sulfide availability protect the
      endothelium from redox stress. Here we show that the transsulfuration enzymes,
      cystathionine beta-synthase and cystathionine gamma-lyase, are secreted by
      microvascular endothelial cells and hepatocytes, circulate as members of the
      plasma proteome, and actively produce hydrogen sulfide from homocysteine in human
      blood. We further demonstrate that extracellular transsulfuration regulates cell
      function when the endothelium is challenged with homocysteine and that hydrogen
      sulfide protects the endothelium from serum starvation and from hypoxia
      reoxygenation injury. These novel findings uncover a unique set of opportunities
      to explore innovative clinical diagnostics and therapeutic strategies in the
      approach to homocysteine-related conditions such as atherosclerosis, thrombosis,
      and dementia.

PMID- 20817828
TI  - Low-intensity aerobic interval training attenuates pathological left ventricular
      remodeling and mitochondrial dysfunction in aortic-banded miniature swine.
AB  - Cardiac hypertrophy in response to hypertension or myocardial infarction is a
      pathological indicator associated with heart failure (HF). A central component of
      the remodeling process is the loss of cardiomyocytes via cell death pathways
      regulated by the mitochondrion. Recent evidence has indicated that exercise
      training can attenuate or reverse pathological remodeling, creating a
      physiological phenotype. The purpose of this study was to examine left
      ventricular (LV) function, remodeling, and cardiomyocyte mitochondrial function
      in aortic-banded (AB) sedentary (HFSED; n = 6), AB exercise-trained (HFTR, n =
      5), and control sedentary (n = 5) male Yucatan miniature swine. LV hypertrophy
      was present in both AB groups before the start of training, as indicated by
      increases in LV end-diastolic volume, LV end-systolic volume (LVESV), and LV end
      systolic dimension (LVESD). Exercise training (15 wk) prevented further increases
      in LVESV and LVESD (P < 0.05). The heart weight-to-body weight ratio, LV + septum
      to-body weight ratio, LV + septum-to-right ventricle ratio, and cardiomyocyte
      cross-sectional area were increased in both AB groups postmortem regardless of
      training status. Preservation of LV function after exercise training, as
      indicated by the maintenance of fractional shortening, ejection fraction, and
      mean wall shortening and increased stroke volume, was associated with an
      attenuation of the increased LV fibrosis (23%) and collagen (36%) observed in
      HFSED animals. LV mitochondrial dysfunction, as measured by Ca(2+)-induced
      mitochondrial permeability transition, was increased in HFSED (P < 0.05) but not
      HFTR animals. In conclusion, low-intensity interval exercise training preserved
      LV function as exemplified by an attenuation of fibrosis, maintenance of a
      positive inotropic state, and inhibition of mitochondrial dysfunction, providing
      further evidence of the therapeutic potential of exercise in a clinical setting.

PMID- 20817829
TI  - Novel role of endothelial BKCa channels in altered vasoreactivity following
      hypoxia.
AB  - The systemic vasculature exhibits attenuated vasoconstriction following hypobaric
      chronic hypoxia (CH) that is associated with endothelium-dependent vascular
      smooth muscle (VSM) cell hyperpolarization. We hypothesized that increased
      activity of endothelial cell (EC) large-conductance, calcium-activated potassium
      (BK(Ca)) channels contributes to this response. Gracilis resistance arteries from
      hypobaric CH (barometric pressure = 380 mmHg for 48 h) rats demonstrated reduced
      myogenic reactivity and hyperpolarized VSM membrane potential (E(m)) compared
      with controls under normoxic ex vivo conditions. These differences were
      eliminated by endothelial disruption. In the presence of cyclooxygenase and
      nitric oxide synthase inhibition, combined intraluminal administration of the
      intermediate and small-conductance, calcium-activated K(+) channel blockers TRAM
      34 and apamin was without effect on myogenic responsiveness and VSM E(m) in both
      groups; however, these variables were normalized in CH arteries by intraluminal
      administration of the BK(Ca) inhibitor iberiotoxin (IBTX). Basal EC E(m) was
      hyperpolarized in arteries from CH rats compared with controls and was restored
      by IBTX, but not by TRAM-34/apamin. K(+) channel blockers were without effect on
      EC basal E(m) in controls. Similarly, IBTX blocked acetylcholine-induced dilation
      in arteries from CH rats, but was without effect in controls, whereas TRAM
      34/apamin eliminated dilation in controls. Acetylcholine-induced EC
      hyperpolarization and calcium responses were inhibited by IBTX in CH arteries and
      by TRAM-34/apamin in controls. Patch-clamp experiments on freshly isolated ECs
      demonstrated greater K(+) current in cells from CH rats that was normalized by
      IBTX. IBTX was without effect on K(+) current in controls. We conclude that
      hypobaric CH induces increased endothelial BK(Ca) channel activity that
      contributes to reduced myogenic responsiveness and EC and VSM cell
      hyperpolarization.

PMID- 20817830
TI  - Augmented EDHF signaling in rat uteroplacental vasculature during late pregnancy.
AB  - A successful pregnancy outcome relies on extensive maternal cardiovascular
      adaptation, including enhanced uteroplacental vasodilator mechanisms. The
      objective of the present study was to determine the contribution of the
      endothelium-derived hyperpolarizing factor (EDHF) signaling in pregnancy-enhanced
      uterine vasodilation, to define the role of Ca(2+)-activated K(+) channels in
      mediating EDHF effects, and to explore the impact of endothelial Ca(2+) signaling
      in pregnancy-specific upregulation of EDHF. Fura 2-based measurements of smooth
      muscle cell (SMC) and endothelial cell cytosolic Ca(2+) concentration
      ([Ca(2+)](i)) were performed simultaneously with measurements of the diameter of
      uterine radial arteries from nonpregnant (NP) and late pregnant (LP) rats.
      Changes in SMC membrane potential of pressurized arteries from LP rats were
      assessed using glass microelectrodes. After blockade of nitric oxide and
      prostacyclin production, a cumulative application of ACh induced rapid and
      effective dilatation of uterine vessels from both NP and LP rats. This
      vasodilation was associated with SMC hyperpolarization and SMC [Ca(2+)](i)
      reduction and was abolished by a high-K(+) solution, demonstrating that N(G)
      nitro-L-arginine (L-NNA)- and indomethacin-resistant responses are attributable
      to EDHF. Pregnancy significantly potentiates EDHF-mediated vasodilation in part
      due to enhanced endothelial Ca(2+) signaling. L-NNA- and indomethacin-resistant
      responses were insensitive to iberiotoxin but abolished by a combined treatment
      with apamin and charybdotoxin, supporting the key role of small- and intermediate
      conductance K(+) channels in mediating EDHF signaling in the maternal uterine
      resistance vasculature.

PMID- 20817831
TI  - Nitric oxide, but not vasodilating prostaglandins, contributes to the improvement
      of exercise hyperemia via ascorbic acid in healthy older adults.
AB  - Acute ascorbic acid (AA) administration increases muscle blood flow during
      dynamic exercise in older adults, and this is associated with improved
      endothelium-dependent vasodilation. We directly tested the hypothesis that
      increase in muscle blood flow during AA administration is mediated via
      endothelium-derived vasodilators nitric oxide (NO) and prostaglandins (PGs). In
      14 healthy older adults (64 +/- 3 yr), we measured forearm blood flow (FBF;
      Doppler ultrasound) during rhythmic handgrip exercise at 10% maximum voluntary
      contraction. After 5-min steady-state exercise with saline, AA was infused via
      brachial artery catheter for 10 min during continued exercise, and this increased
      FBF ~25% from 132 +/- 16 to 165 +/- 20 ml/min (P < 0.05). AA was infused for the
      remainder of the study. Next, subjects performed a 15-min exercise bout in which
      AA + saline was infused for 5 min, followed by 5 min of the nitric oxide synthase
      (NOS) inhibitor N(G)-monomethyl-l-arginine (l-NMMA) and then 5 min of the
      cyclooxygenase inhibitor ketorolac (group 1). The order of inhibition was
      reversed in eight subjects (group 2). In group 1, independent NOS inhibition
      reduced steady-state FBF by ~20% (P < 0.05), and subsequent PG inhibition had no
      impact on FBF (Delta 3 +/- 5%). Similarly, in group 2, independent PG inhibition
      had little effect on FBF (Delta -4 +/- 4%), whereas subsequent NO inhibition
      significantly decreased FBF by ~20% (P < 0.05). In a subgroup of five subjects,
      we inhibited NO and PG synthesis before AA administration. In these subjects,
      there was a minimal nonsignificant improvement in FBF with AA infusion (Delta 7
      +/- 3%; P = nonsignificant vs. zero). Together, our data indicate that the
      increase in muscle blood flow during dynamic exercise with acute AA
      administration in older adults is mediated primarily via an increase in the
      bioavailability of NO derived from the NOS pathway.

PMID- 20817832
TI  - Inhibition of collar-induced carotid atherosclerosis by recombinant apoA-I
      cysteine mutants in apoE-deficient mice.
AB  - The previous studies in our laboratory revealed that seven cysteine mutants of
      apolipoprotein A-I (apoA-I) have different structural features and biological
      activities in vitro and in vivo. To investigate the potential cardioprotective
      effects of apolipoprotein A-I(N74C) [apoA-I(N74C)], we examined the anti
      inflammatory, antioxidant, and antiatherosclerotic effects of this cysteine
      mutant in a rapid atherosclerosis model induced by perivascular carotid collar
      placement in apoE-/- mice. Lipid-free apoA-I(N74C) showed a significant increased
      antioxidant potency in low density lipoprotein (LDL) oxidation in vitro and
      reduced intracellular lipid accumulation in THP-1-derived macrophages, relative
      to wild-type apoA-I (apoA-Iwt). Mice injected with recombinant HDL (rHDL)
      reconstituted with apoA-I(N74C) (named rHDL74) through tail veins (40 mg/kg of
      body weight, three injections) had a significant lower level of serum interleukin
      6 (IL-6) and enhanced serum antioxidation compared with mice receiving rHDL
      reconstituted with apoA-Iwt (named rHDLwt). Moreover, compared with rHDLwt, the
      rHDL74 in vivo injection resulted in a significant decrease in plaque size, ratio
      of aorta intima to media, arterial remodeling, and macrophage content in lesions.
      In summary, intravenous injection with rHDL74 reconstituted with apoA-I cysteine
      mutant apoA-I (N74C) dramatically delays the development of atherosclerosis
      induced by perivascular carotid collar placement and reduces vascular remodeling
      in the carotid artery in apoE-/- mice.

PMID- 20817833
TI  - Quantification of seminolipid by LC-ESI-MS/MS-multiple reaction monitoring:
      compensatory levels in Cgt(+/-) mice.
AB  - Seminolipid, also known as sulfogalactosylglycerolipid (SGG), plays important
      roles in male reproduction. Therefore, an accurate and sensitive method for SGG
      quantification in testes and sperm is needed. Here we compare SGG quantitation by
      the traditional colorimetric Azure A assay with LC-ESI-MS/MS using multiple
      reaction monitoring (MRM). Inclusion of deuterated SGG as the internal standard
      endowed accuracy to the MRM method. The results showed reasonable agreement
      between the two procedures for purified samples, but for crude lipid extracts,
      the colorimetric assay significantly overestimated the SGG content. Using ESI
      MS/MS MRM, C16:0-alkyl/C16:0-acyl SGG of Cgt(+/-) mice was quantified to be
      406.06 +/- 23.63 MUg/g testis and 0.13 +/- 0.02 MUg/million sperm, corresponding
      to 78% and 87% of the wild-type values, respectively. CGT (ceramide
      galactosyltransferase) is a critical enzyme in the SGG biosynthesis pathway. Cgt
      /- males depleted of SGG are infertile due to spermatogenesis arrest. However,
      Cgt(+/-) males sire offspring. The higher than 50% expression level of SGG in
      Cgt(+/-) animals, compared with the wild-type expression, might be partly due to
      compensatory translation of the active CGT enzyme. The results also indicated
      that 78% of SGG levels in Cgt(+/-) mice were sufficient for normal
      spermatogenesis.

PMID- 20817834
TI  - Sphingomonas xinjiangensis sp. nov., isolated from desert sand.
AB  - A Gram-negative, aerobic, motile, Sphingomonas-like rod, strain 10-1-84(T), was
      isolated from a sand sample collected from the desert of Xinjiang, China. The
      isolate contained Q-10 as the predominant ubiquinone and C(18 : 1)omega7c, C(16 :
      0), C(16 : 1)omega7c and C(14 : 0) 2-OH as the major fatty acids. The polyamine
      pattern contained predominantly sym-homospermidine. The main polar lipids were
      sphingoglycolipid, phosphatidylcholine, phosphatidylglycerol,
      diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidyldimethylethanolamine and an unknown polar lipid. The DNA G+C content
      was 63.3 mol%. 16S rRNA gene sequence similarity between strain 10-1-84(T) and
      the type strains of species of the genus Sphingomonas ranged from 91.11 to 96.54
      %. Phylogenetic analysis based on 16S rRNA gene sequence indicated that strain 10
      1-84(T) belonged to the genus Sphingomonas. On the basis of phylogenetic analysis
      and physiological and biochemical characterization, strain 10-1-84(T) represents
      a novel species of the genus Sphingomonas, for which the name Sphingomonas
      xinjiangensis sp. nov. is proposed. The type strain is 10-1-84(T) ( = CCTCC AB
      208035(T)  = NRRL B-51332(T)).

PMID- 20817835
TI  - Nocardia endophytica sp. nov., an endophytic actinomycete isolated from the oil
      seed plant Jatropha curcas L.
AB  - A novel actinomycete, designated strain KLBMP 1256(T), was isolated from a
      surface-sterilized stem of the oil-seed plant Jatropha curcas L. collected from
      Sichuan Province, south-west China, and was characterized to determine its
      taxonomic position. Phylogenetic analyses based on 16S rRNA gene sequences
      indicated that the isolate was closely related to members of the genus Nocardia
      in the family Nocardiaceae, being most closely related to Nocardia callitridis
      CAP 290(T) (98.4 % similarity) and Nocardia nova JCM 6044(T) (97.5 %). Levels of
      16S rRNA gene sequence similarity between strain KLBMP 1256(T) and the type
      strains of other recognized species of the genus Nocardia were less than 97 %.
      Chemotaxonomic data supported the affiliation of the new isolate to the genus
      Nocardia. However, the novel strain could be distinguished from its closest
      phylogenetic neighbour, N. callitridis CAP 290(T), by a range of phenotypic
      properties. The combination of low DNA-DNA relatedness values and phenotypic
      differences from N. callitridis CAP 290(T) indicated that strain KLBMP 1256(T)
      represents a novel species of the genus Nocardia, for which the name Nocardia
      endophytica sp. nov. is proposed. The type strain is KLBMP 1256(T) ( = KCTC
      19777(T)  = CCTCC AA 2010004(T)).

PMID- 20817836
TI  - Cryobacterium arcticum sp. nov., a psychrotolerant bacterium from an Arctic soil.
AB  - A psychrotolerant, Gram-stain-positive, yellow-pigmented, aerobic rod, designated
      SK1(T), was isolated from a soil sample collected from Store Koldewey, north-east
      Greenland. Cells were catalase- and methyl red-positive, produced H(2)S and
      produced acid from glucose, mannitol and salicin. Strain SK1(T) was able to grow
      between -6 and 28  degrees C, with an optimum at 20  degrees C. The isolate
      contained 2,4-diaminobutyrate, glycine, alanine and glutamic acid in the cell
      wall and the major menaquinones were MK-10 and MK-11. Identified polar lipids
      were phosphatidylglycerol and diphosphatidylglycerol. The major fatty acids were
      anteiso-C(15 : 0) (53.5 %), anteiso-C(17 : 0) (17.0 %) and C(18 : 0) (12.1 %).
      The genomic DNA G+C content was 67.8 mol%. Strain SK1(T) showed the highest 16S
      rRNA gene sequence similarity with Cryobacterium psychrotolerans 0549(T) (97.6 %)
      and Cryobacterium roopkundense RuGl7(T) (96.8 %). Considering morphological,
      physiological, biochemical and chemotaxonomic characters and phylogenetic
      analysis, strain SK1(T) represents a novel species in the genus Cryobacterium,
      for which the name Cryobacterium arcticum sp. nov. is proposed. The type strain
      is SK1(T) ( = DSM 22823(T)  = NCCB 100316(T)).

PMID- 20817837
TI  - Pseudomonas toyotomiensis sp. nov., a psychrotolerant facultative alkaliphile
      that utilizes hydrocarbons.
AB  - A psychrotolerant, facultatively alkaliphilic strain, HT-3(T), was isolated from
      a sample of soil immersed in hot-spring water containing hydrocarbons in
      Toyotomi, Hokkaido, Japan. 16S rRNA gene sequence-based phylogeny suggested that
      strain HT-3(T) is a member of the genus Pseudomonas and belongs to the
      Pseudomonas oleovorans group. Cells of the isolate were Gram-negative, aerobic,
      straight rods, motile by a single polar flagellum. The strain grew at 4-42 
      degrees C, with optimum growth at 35  degrees C at pH 7, and at pH 6-10. It
      hydrolysed Tweens 20, 40, 60 and 80, but not casein, gelatin, starch or DNA. Its
      major isoprenoid quinone was ubiquinone-9 (Q-9) and the DNA G+C content was 65.1
      mol%. The whole-cell fatty acid profile consisted mainly of C(16 : 0), C(16 :
      1)omega9c and C(18 : 1)omega9c. Phylogenetic analyses based on gyrB, rpoB and
      rpoD sequences revealed that the isolate could be discriminated from Pseudomonas
      species that exhibited more than 97 % 16S rRNA gene sequence similarity and
      phylogenetic neighbours belonging to the P. oleovorans group including the
      closest relative of the isolate, Pseudomonas alcaliphila. DNA-DNA hybridization
      with P. alcaliphila AL15-21(T) revealed 51 +/- 5 % relatedness. Owing to
      differences in phenotypic properties and phylogenetic analyses based on
      multilocus gene sequence analysis and DNA-DNA relatedness data, the isolate
      merits classification in a novel species, for which the name Pseudomonas
      toyotomiensis sp. nov. is proposed. The type strain is HT-3(T) ( = JCM 15604(T) 
      = NCIMB 14511(T)).

PMID- 20817838
TI  - Classification of organisms previously reported as the SP and Stewart-Letscher
      groups, with descriptions of Necropsobacter gen. nov. and of Necropsobacter
      rosorum sp. nov. for organisms of the SP group.
AB  - To allow classification of bacteria previously reported as the SP group and the
      Stewart-Letscher group, 35 isolates from rodents (21), rabbits (eight), a dog and
      humans (five) were phenotypically and genotypically characterized. Comparison of
      partial rpoB sequences showed that 34 of the isolates were closely related,
      demonstrating at least 97.4 % similarity. 16S rRNA gene sequence comparison of 20
      selected isolates confirmed the monophyly of the SP group and revealed 98.5 %-100
      % similarity between isolates. A blast search using the 16S rRNA gene sequences
      showed that the highest similarity outside the SP group was 95.5 % to an
      unclassified rat isolate. The single strain, P625, representing the Stewart
      Letscher group showed the highest 16S rRNA gene similarity (94.9-95.5 %) to
      members of the SP group. recN gene sequence analysis of 11 representative strains
      resulted in similarities of 97-100 % among the SP group strains, which showed 80
      % sequence similarity to the Stewart-Letscher group strain. Sequence similarity
      values based on the recN gene, indicative for whole genome similarity, showed the
      SP group being clearly separated from established genera, whereas the Stewart
      Letscher group strain was associated with the SP group. A new genus,
      Necropsobacter gen. nov., with only one species, Necropsobacter rosorum sp. nov.,
      is proposed to include all members of the SP group. The new genus can be
      separated from existing genera of the family Pasteurellaceae by at least three
      phenotypic characters. The most characteristic properties of the new genus are
      that haemolysis is not observed on bovine blood agar, positive reactions are
      observed in the porphyrin test, acid is produced from (+)-L-arabinose, (+)-D
      xylose, dulcitol, (+)-D-galactose, (+)-D-mannose, maltose and melibiose, and
      negative reactions are observed for symbiotic growth, urease, ornithine
      decarboxylase and indole. Previous publications have documented that both
      ubiquinones and demethylmenaquinone were produced by the proposed type strain of
      the new genus, Michel A/76(T), and that the major polyamine of representative
      strains (type strain not included) of the genus is 1,3-diaminopropane, spermidine
      is present in moderate amounts and putrescine and spermine are detectable only in
      minor amounts. The major fatty acids of strain Michel A/76(T) are C(14 : 0), C(16
      : 0), C(16:1)omega7c and summed feature C(14 : 0) 3-OH/iso-C(16 : 1) I. This
      fatty acid profile is typical for members of the family Pasteurellaceae. The G+C
      content of DNA of strain Michel A/76(T) was estimated to be 52.5 mol% in a
      previous investigation. The type strain is P709(T) ( = Michel A/76(T)  = CCUG
      28028(T)  = CIP 110147(T)  = CCM 7802(T)).

PMID- 20817839
TI  - Haloferula luteola sp. nov., an endophytic bacterium isolated from the root of a
      halophyte, Rosa rugosa, and emended description of the genus Haloferula.
AB  - A Gram-negative, non-spore-forming, endophytic bacterium, strain YC6886(T), was
      isolated from the root of a halophyte, Rosa rugosa, which inhabits coastal areas
      of Namhae Island off the southern coast of Korea. Cells were non-motile,
      obligately aerobic rods and formed pale-yellow colonies. The isolate grew at 4-32
      degrees C (optimum 25-28  degrees C) and at pH 6.5-9.5 (optimum pH 7.5) and grew
      optimally with 2-3 % (w/v) NaCl, but NaCl was not an absolute requirement for
      growth. Strain YC6886(T) produced yellow carotenoid pigments. Strain YC6886(T)
      exhibited the highest 16S rRNA gene sequence similarity with Haloferula
      sargassicola MN1-1037(T) (97.4 %). Sequence similarities between strain YC6886(T)
      and other members of the genus Haloferula were 93.9-94.7 %. DNA-DNA relatedness
      between strain YC6886(T) and H. sargassicola KCTC 22202(T) and Haloferula rosea
      KCTC 22201(T) was 27 and 15 %, respectively. The major fatty acids were iso-C(14
      : 0), C(16 : 0) and C(16 : 1)omega9c and minor components were C(14 : 0), C(18 :
      0) and anteiso-C(15 : 0). The major respiratory quinone was menaquinone 9 and the
      DNA G+C content was 58.5 mol%. The polar lipid profile was composed of
      diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, an
      unknown phospholipid and an unknown phosphoglycolipid. On the basis of
      phenotypic, chemotaxonomic, DNA-DNA hybridization and phylogenetic analysis,
      strain YC6886(T) represents a novel species in the genus Haloferula, for which
      the name Haloferula luteola sp. nov. is proposed. The type strain is YC6886(T) (
      = KCTC 22447(T)  = DSM 21608(T)). An emended description of the genus Haloferula
      is also presented.

PMID- 20817840
TI  - Pelagibacterium halotolerans gen. nov., sp. nov. and Pelagibacterium luteolum sp.
      nov., novel members of the family Hyphomicrobiaceae.
AB  - Two Gram-negative, motile, aerobic bacterial strains, designated B2(T) and
      1_C16_27(T), were respectively isolated from a seawater sample collected from the
      East China Sea and a semi-coke sample from north-eastern Estonia. Their genetic,
      phenotypic and chemotaxonomic properties were studied. The isolates were short
      rods with polar flagella and were positive for catalase and oxidase activities. Q
      10 was the predominant respiratory ubiquinone. The major polar lipids were
      phosphatidylglycerol, diphosphatidylglycerol and two unidentified glycolipids.
      The major fatty acids were nonadecanoic (C(19 : 0) cyclo), octadecanoic (C(18 :
      0) and C(18 : 0) 3-OH), octadecenoic (C(18 : 1)) and hexadecanoic (C(16 : 0))
      acids. The G+C content of the genomic DNA was 58.1-59.3 mol%. 16S rRNA gene
      sequence analysis revealed that the two isolates represent a distinct lineage
      within the family Hyphomicrobiaceae. The phylogenetically closest relatives were
      Cucumibacter (92.7-93.7 % 16S rRNA gene sequence similarity), Devosia (92.9-94.4
      %) and Zhangella (91.7-92.1 %). Differential phenotypic properties, together with
      phylogenetic and genetic distinctiveness, revealed that strains B2(T) and
      1_C16_27(T) could be differentiated from each other and from members of the
      genera Cucumibacter, Devosia and Zhangella. Therefore, it is proposed that
      strains B2(T) and 1_C16_27(T) represent two novel species in a new genus, for
      which the names Pelagibacterium halotolerans gen. nov., sp. nov. (the type
      species; type strain B2(T)  = CGMCC 1.7692(T)  = JCM 15775(T)) and
      Pelagibacterium luteolum sp. nov. (type strain 1_C16_27(T)  = CGMCC 1.10267(T)  =
      JCM 16552(T)  = CELMS EEUT 1C1627(T)) are proposed.

PMID- 20817841
TI  - Blastochloris gulmargensis sp. nov., isolated from an epilithic phototrophic
      biofilm.
AB  - A novel Gram-negative, motile, bacteriochlorophyll b-containing purple non-sulfur
      bacterium, strain JA248(T), was isolated from phototrophic enrichments of a
      yellow-green epilithic biofilm sample collected from Gulmarg, India. The genomic
      DNA G+C content of strain JA248(T) was 63.8 mol%. A phylogenetic tree based on
      16S rRNA gene sequence analysis showed that strain JA248(T) had highest
      similarity to members of the genus Blastochloris and was closely related to
      Blastochloris sulfoviridis DSM 729(T) (98.5 % sequence similarity) and
      Blastochloris viridis DSM 133(T) (98.4 %) of the class Alphaproteobacteria.
      Strain JA248(T) was characterized based on polyphasic taxonomy, and distinct
      phenotypic and molecular differences based on DNA-DNA hybridization (relatedness
      of <46.5 % with the two species of the genus Blastochloris), multilocus sequence
      analysis, and phenotypic and chemotaxonomic evidence separated strain JA248(T)
      from other species of the genus Blastochloris. Strain JA248(T) therefore
      represents a novel species in the genus Blastochloris, for which the name
      Blastochloris gulmargensis sp. nov. is proposed. The type strain is JA248(T) ( =
      JCM 14795(T)  = DSM 19786(T)).

PMID- 20817842
TI  - Relationship of Bacillus amyloliquefaciens clades associated with strains DSM 7T
      and FZB42T: a proposal for Bacillus amyloliquefaciens subsp. amyloliquefaciens
      subsp. nov. and Bacillus amyloliquefaciens subsp. plantarum subsp. nov. based on
      complete genome sequence comparisons.
AB  - The whole-genome-sequenced rhizobacterium Bacillus amyloliquefaciens FZB42(T)
      (Chen et al., 2007) and other plant-associated strains of the genus Bacillus
      described as belonging to the species Bacillus amyloliquefaciens or Bacillus
      subtilis are used commercially to promote the growth and improve the health of
      crop plants. Previous investigations revealed that a group of strains represented
      a distinct ecotype related to B. amyloliquefaciens; however, the exact taxonomic
      position of this group remains elusive (Reva et al., 2004). In the present study,
      we demonstrated the ability of a group of Bacillus strains closely related to
      strain FZB42(T) to colonize Arabidopsis roots. On the basis of their phenotypic
      traits, the strains were similar to Bacillus amyloliquefaciens DSM 7(T) but
      differed considerably from this type strain in the DNA sequences of genes
      encoding 16S rRNA, gyrase subunit A (gyrA) and histidine kinase (cheA).
      Phylogenetic analysis performed with partial 16S rRNA, gyrA and cheA gene
      sequences revealed that the plant-associated strains of the genus Bacillus,
      including strain FZB42(T), formed a lineage, which could be distinguished from
      the cluster of strains closely related to B. amyloliquefaciens DSM 7(T). DNA-DNA
      hybridizations (DDH) performed with genomic DNA from strains DSM 7(T) and
      FZB42(T) yielded relatedness values of 63.7-71.2 %. Several methods of genomic
      analysis, such as direct whole-genome comparison, digital DDH and microarray
      based comparative genomichybridization (M-CGH) were used as complementary tests.
      The group of plant-associated strains could be distinguished from strain DSM 7(T)
      and the type strain of B. subtilis by differences in the potential to synthesize
      non-ribosomal lipopeptides and polyketides. Based on the differences found in the
      marker gene sequences and the whole genomes of these strains, we propose two
      novel subspecies, designated B. amyloliquefaciens subsp. plantarum subsp. nov.,
      with the type strain FZB42(T) ( = DSM 23117(T) = BGSC 10A6(T)), and B.
      amyloliquefaciens subsp. amyloliquefaciens subsp. nov., with the type strain DSM
      7(T)( = ATCC 23350(T) = Fukumoto Strain F(T)), for plant-associated and non-plant
      associated representatives, respecitvely. This is in agreement with results of
      DDH and M-CGH tests and the MALDI-TOF MS of cellular components, all of which
      suggested that the ecovars represent two different subspecies.

PMID- 20817843
TI  - Peptoniphilus methioninivorax sp. nov., a Gram-positive anaerobic coccus isolated
      from retail ground beef.
AB  - Strain NRRL B-23883(T) was isolated from retail ground beef as part of a study on
      the genetic diversity of Clostridium perfringens. The strain was found to be a
      strictly anaerobic, Gram-positive coccus that was able to utilize peptone as a
      sole carbon source. Analysis of the 16S rRNA gene sequence revealed that the
      strain was closely related to species within the genera Peptoniphilus and
      Anaerosphaera, but it was substantially different from the closest recognized
      species by nearly 10 % sequence divergence. The strain was also found to be
      closely related (>99 % sequence similarity) to an uncultured bacterial strain
      that was sequenced from a 16S rRNA gene clone library constructed to characterize
      the bacterial community of faeces from a captive spotted hyena. Strain NRRL B
      23883(T) shared the peptidoglycan type A4beta, l-Orn-d-Glu with members of the
      genus Peptoniphilus. Further phenotypic analysis revealed that strain NRRL B
      23883(T) was able to utilize glycyl l-methionine as a sole carbon source, in
      contrast to other species of the genus Peptoniphilus. Therefore, it is proposed
      that the isolate represents a novel species, Peptoniphilus methioninivorax sp.
      nov.; the type strain is NRRL B-23883(T) ( = DSM 22461(T)).

PMID- 20817844
TI  - Emended descriptions of Geobacillus thermoleovorans and Geobacillus
      thermocatenulatus.
AB  - Nineteen thermophilic, aerobic, endospore-forming bacterial strains were
      subjected to 16S rRNA gene sequence analysis. Eight of these strains had been
      received as cultures of Geobacillus kaustophilus, G. lituanicus, G.
      stearothermophilus, 'G. thermoleovorans subsp. stromboliensis', G. vulcani,
      'Bacillus caldolyticus', 'B. caldotenax' and 'B. caldovelox', but they showed
      close relationships with the type strain of G. thermoleovorans, as did two other
      strains received as G. thermoleovorans. All strains underwent further taxonomic
      analysis by API and other phenotypic tests and fatty acid methyl ester analysis,
      and selected strains were analysed for their polar lipids and for DNA
      relatedness. The 11 strains that formed the G. thermoleovorans 16S rRNA cluster
      also showed some phenotypic similarities, and DNA relatedness data support the
      reassignment of the strains received as G. kaustophilus, G. lituanicus, 'G.
      thermoleovorans subsp. stromboliensis', G. vulcani, 'B. caldolyticus', 'B.
      caldotenax' and 'B. caldovelox', and one of the G. stearothermophilus strains, as
      members of the species G. thermoleovorans. Four other strains received as G.
      kaustophilus were misnamed; two were identified as G. stearothermophilus and two
      appeared to be closely related to Anoxybacillus rupiensis. One strain received as
      G. stearothermophilus remained unidentified. On the basis of a single strain,
      Geobacillus thermocatenulatus was shown to represent a distinct species, but
      study of the type strain of Geobacillus gargensis showed this species to be a
      later heterotypic synonym of Geobacillus thermocatenulatus. Emended descriptions
      of Geobacillus thermoleovorans and Geobacillus thermocatenulatus are therefore
      presented.

PMID- 20817845
TI  - A 12-year long-term retrospective analysis of the use of radiofrequency nerve
      ablation for the treatment of neurogenic heel pain.
AB  - The authors discuss their rationale for the use of radiofrequency nerve ablation
      (RFNA) in the treatment of chronic neurogenic heel pain. Patients treated for
      plantar fasciitis who fail to improve after conservative and/ or surgical
      treatment should be reevaluated for a coexistent nerve entrapment. The results of
      a retrospective study of 82 patients who have undergone RFNA are presented. The
      patients were followed at 5, 10, and 12 years after the procedure. An evaluation
      of medical records was performed as a means of inclusion in this study. A
      standardized telephone interview was then done, and subjectively scored responses
      of the patients were recorded and analyzed. Of the patients, 89% reported no
      recurrence of pain after 5, 10, and 12 years postoperatively. The procedure is
      relatively easy to perform and involves inserting a 22-gauge cannula with an
      electrode into the areas of pain. This is done under general anesthesia. It takes
      approximately 15 to 20 minutes per heel to perform, depending on how many sites
      of tenderness have been identified. The patient is discharged with a minimal
      bandage and returns to shoe gear immediately following the procedure. The success
      rate with RFNA appears to be quite high with fewer associated risks and less post
      operative morbidity.

PMID- 20817846
TI  - Value of ultrasonography for detecting ligament damage in athletes with chronic
      ankle instability compared to computed arthrotomography.
AB  - Ankle sprains may be followed by chronic pain and/or instability, which may
      induce substantial disability, most notably in athletes. Chronic ankle
      instability promotes the development of cartilage lesions in athletes. Therefore,
      accurate evaluation of the ankle ligaments is crucial to the optimal management
      of chronic ankle instability after a sprain. The objective of this study was to
      assess the performance of ultrasonography in assessing damage to the anterior
      talofibular ligament (ATFL) in athletes with chronic ankle instability after a
      sprain. Consecutive patients seen at the author's clinic for ankle instability
      more than 3 months after a sprain underwent ultrasonography and computed
      arthrotomography after a clinical anterior drawer stress test. Cohen's kappa was
      computed to evaluate agreement between the 2 imaging modalities. This study
      included 56 patients, 46 men and 10 women, aged 15 to 69 years (mean, 30.1 +/-
      10.6 years). Mean time from the sprain to imaging was 7.6 +/- 4.02 months. ATFL
      damage was found by ultrasonography in 34 (61%) of 56 patients and by computed
      arthrotomography in 39 of 55 patients (71%; kappa = 0.76). Cartilage damage was
      visualized by computed arthrotomography in 14 (25%) patients, all of whom had
      ATFL damage. Agreement was substantial (kappa = 0.76) between ultrasonography and
      computed arthrotomography for assessing the ATFL. The data support the use of
      ultra-sonography as the second-line investigation after a standard radiographic
      assessment in athletes with chronic ankle instability after a sprain.

PMID- 20817847
TI  - Incidence of plantar fascia ruptures following corticosteroid injection.
AB  - Plantar fasciitis is commonly treated with corticosteroid injections to decrease
      pain and inflammation. Therapeutic benefits often vary in terms of efficacy and
      duration. Rupture of the plantar fascia has been reported as a possible
      complication following corticosteroid injection. A retrospective chart review of
      120 patients who received corticosteroid injection for plantar fasciitis was
      performed at the authors' institution to determine the incidence of plantar
      fascia rupture. The plantar fascia rupture was diagnosed clinically and confirmed
      with magnetic resonance imaging. Various factors were analyzed, including the
      number of injections, interval between injections, body mass index (BMI), and
      activity level. Four patients (2.4%) consequently experienced plantar fascia
      rupture following an average of 2.67 injections. The average BMI of these
      patients was 38.6 kg/m2. The authors conclude that corticosteroid injection
      therapy appears to be a safe and effective form of nonoperative treatment with
      minimal complications and a relatively low incident of plantar fascia rupture.

PMID- 20817849
TI  - Antithrombin-heparin covalent complex reduces microemboli during cardiopulmonary
      bypass in a pig model.
AB  - Transcranial Doppler-detected high-intensity transient signals (HITS) during
      cardiopulmonary bypass (CPB) surgery have been associated with postoperative
      neurocognitive dysfunction, suggesting microemboli in the brain could be a
      contributing factor. HITS occur despite administration of unfractionated heparin
      (UFH). This study was done to determine whether antithrombin-heparin covalent
      complex (ATH), a more potent anticoagulant than heparin, can reduce HITS during
      CPB. In a pig CPB model, ATH, UFH, or UFH + antithrombin (AT) was intravenously
      administered to female Yorkshire pigs after sternotomy. Twenty minutes later,
      hypothermic CPB was initiated and continued for 1.25 hours, then normothermia was
      re-established for 45 minutes. Protamine sulfate was given to neutralize the
      anticoagulants, and pigs were allowed to recover. HITS were monitored using an
      arterial flow probe placed over the carotid artery. Compared with UFH (300 or
      1000 U/kg), ATH reduced the number of HITS during CPB in a dose-dependent manner.
      AT (3 mg/kg) + UFH (300 U/kg) resulted in an intermediate HITS rate between UFH
      and ATH (2 mg/kg in terms of AT). Examination of brain sections for emboli
      formation confirmed that, similar to HITS, number of thrombi decreased in direct
      proportion to ATH dosage. These results support the hypotheses that the majority
      of HITS represent thromboemboli and that ATH reduces emboli formation during CPB.

PMID- 20817848
TI  - Arabidopsis LIM proteins: a family of actin bundlers with distinct expression
      patterns and modes of regulation.
AB  - Recently, a number of two LIM-domain containing proteins (LIMs) have been
      reported to trigger the formation of actin bundles, a major higher-order
      cytoskeletal assembly. Here, we analyzed the six Arabidopsis thaliana LIM
      proteins. Promoter-beta-glucuronidase reporter studies revealed that WLIM1,
      WLIM2a, and WLIM2b are widely expressed, whereas PLIM2a, PLIM2b, and PLIM2c are
      predominantly expressed in pollen. LIM-green fluorescent protein (GFP) fusions
      all decorated the actin cytoskeleton and increased actin bundle thickness in
      transgenic plants and in vitro, although with different affinities and
      efficiencies. Remarkably, the activities of WLIMs were calcium and pH
      independent, whereas those of PLIMs were inhibited by high pH and, in the case of
      PLIM2c, by high [Ca(2+)]. Domain analysis showed that the C-terminal domain is
      key for the responsiveness of PLIM2c to pH and calcium. Regulation of LIM by pH
      was further analyzed in vivo by tracking GFP-WLIM1 and GFP-PLIM2c during
      intracellular pH modifications. Cytoplasmic alkalinization specifically promoted
      release of GFP-PLIM2c but not GFP-WLIM1, from filamentous actin. Consistent with
      these data, GFP-PLIM2c decorated long actin bundles in the pollen tube shank, a
      region of relatively low pH. Together, our data support a prominent role of
      Arabidopsis LIM proteins in the regulation of actin cytoskeleton organization and
      dynamics in sporophytic tissues and pollen.

PMID- 20817850
TI  - Detection of a novel truncating Merkel cell polyomavirus large T antigen deletion
      in chronic lymphocytic leukemia cells.
AB  - Merkel cell polyomavirus (MCPyV) is detected in approximately 80% of Merkel cell
      carcinomas (MCC). Yet, clonal integration and truncating mutations of the large T
      antigen (LTAg) of MCPyV are restricted to MCC. We tested the presence and
      mutations of MCPyV in highly purified leukemic cells of 70 chronic lymphocytic
      leukemia (CLL) patients. MCPyV was detected in 27.1% (n = 19) of these CLL cases.
      In contrast, MCPyV was detected only in 13.4% of normal controls (P < .036) in
      which no LTAg mutations were found. Mutational analyses revealed a novel 246bp
      LTAg deletion in the helicase gene in 6 of 19 MCPyV-positive CLL cases. 2 CLL
      cases showed concomitant mutated and wild-type MCPyV. Immunohistochemistry
      revealed protein expression of the LTAg in MCPyV-positive CLL cases. The
      detection of MCPyV, including LTAg deletions and LTAg expression in CLL cells
      argues for a potential role of MCPyV in a significant subset of CLL cases.

PMID- 20817851
TI  - Molecular basis of LMAN1 in coordinating LMAN1-MCFD2 cargo receptor formation and
      ER-to-Golgi transport of FV/FVIII.
AB  - The LMAN1-MCFD2 (lectin, mannose binding 1/multiple coagulation factor deficiency
      protein 2) cargo receptor complex transports coagulation factors V (FV) and VIII
      (FVIII) from the endoplasmic reticulum (ER) to the ER-Golgi intermediate
      compartment (ERGIC). LMAN1 (ERGIC-53) is a hexameric transmembrane protein with a
      carbohydrate recognition domain (CRD) on the ER luminal side. Here, we show that
      mutations in the first beta sheet of the CRD abolish MCFD2 binding without
      affecting the mannose binding, suggesting that LMAN1 interacts with MCFD2 through
      its N-terminal beta sheet, consistent with recently reported crystal structures
      of the CRD-MCFD2 complex. Mutations in the Ca(2+)- and sugar-binding sites of the
      CRD disrupt FV and FVIII interactions, without affecting MCFD2 binding. This
      interaction is independent of MCFD2, as LMAN1 mutants defective in MCFD2 binding
      can still interact with FVIII. Thus, the CRD of LMAN1 contains distinct,
      separable binding sites for both its partner protein (MCFD2) and the cargo
      proteins (FV/FVIII). Monomeric LMAN1 mutants are defective in ER exit and unable
      to interact with MCFD2, suggesting that the oligomerization of LMAN1 is necessary
      for its cargo receptor function. These results point to a central role of LMAN1
      in regulating the binding in the ER and the subsequent release in the ERGIC of FV
      and FVIII.

PMID- 20817852
TI  - Axonal alpha7 nicotinic ACh receptors modulate presynaptic NMDA receptor
      expression and structural plasticity of glutamatergic presynaptic boutons.
AB  - In association with NMDA receptors (NMDARs), neuronal alpha7 nicotinic ACh
      receptors (nAChRs) have been implicated in neuronal plasticity as well as
      neurodevelopmental, neurological, and psychiatric disorders. However, the role of
      presynaptic NMDARs and their interaction with alpha7 nAChRs in these
      physiological and pathophysiological events remains unknown. Here we report that
      axonal alpha7 nAChRs modulate presynaptic NMDAR expression and structural
      plasticity of glutamatergic presynaptic boutons during early synaptic
      development. Chronic inactivation of alpha7 nAChRs markedly increased cell
      surface NMDAR expression as well as the number and size of glutamatergic axonal
      varicosities in cortical cultures. These boutons contained presynaptic NMDARs and
      alpha7 nAChRs, and recordings from outside-out pulled patches of enlarged
      presynaptic boutons identified functional NMDAR-mediated currents. Multiphoton
      imaging of presynaptic NMDAR-mediated calcium transients demonstrated
      significantly larger responses in these enlarged boutons, suggesting enhanced
      presynaptic NMDAR function that could lead to increased glutamate release.
      Moreover, whole-cell patch clamp showed a significant increase in synaptic charge
      mediated by NMDAR miniature EPSCs but no alteration in the frequency of AMPAR
      miniature EPSCs, suggesting the selective enhancement of postsynaptically silent
      synapses upon inactivation of alpha7 nAChRs. Taken together, these findings
      indicate that axonal alpha7 nAChRs modulate presynaptic NMDAR expression and
      presynaptic and postsynaptic maturation of glutamatergic synapses, and implicate
      presynaptic alpha7 nAChR/NMDAR interactions in synaptic development and
      plasticity.

PMID- 20817853
TI  - Cell adhesion-dependent membrane trafficking of a binding partner for the
      ebolavirus glycoprotein is a determinant of viral entry.
AB  - Ebolavirus is a hemorrhagic fever virus associated with high mortality. Although
      much has been learned about the viral lifecycle and pathogenesis, many questions
      remain about virus entry. We recently showed that binding of the receptor binding
      region (RBR) of the ebolavirus glycoprotein (GP) and infection by GP
      pseudovirions increase on cell adhesion independently of mRNA or protein
      synthesis. One model to explain these observations is that, on cell adhesion, an
      RBR binding partner translocates from an intracellular vesicle to the cell
      surface. Here, we provide evidence for this model by showing that suspension 293F
      cells contain an RBR binding site within a membrane-bound compartment associated
      with the trans-Golgi network and microtubule-organizing center. Consistently,
      trafficking of the RBR binding partner to the cell surface depends on
      microtubules, and the RBR binding partner is internalized when adherent cells are
      placed in suspension. Based on these observations, we reexamined the claim that
      lymphocytes, which are critical for ebolavirus pathogenesis, are refractory to
      infection because they lack an RBR binding partner. We found that both cultured
      and primary human lymphocytes (in suspension) contain an intracellular pool of an
      RBR binding partner. Moreover, we identified two adherent primate lymphocytic
      cell lines that bind RBR at their surface and strikingly, support GP-mediated
      entry and infection. In summary, our results reveal a mode of determining viral
      entry by a membrane-trafficking event that translocates an RBR binding partner to
      the cell surface, and they suggest that this process may be operative in cells
      important for ebolavirus pathogenesis (e.g., lymphocytes and macrophages).

PMID- 20817854
TI  - Effects of body condition on measures of intramuscular and rump fat, endocrine
      factors, and calving rate of beef cows grazing common bermudagrass or endophyte
      infected tall fescue.
AB  - Multiparous beef cows were managed to achieve marginal (BCS = 4.7 +/- 0.07; n =
      106) or good (BCS = 6.6 +/- 0.06; n = 121) body condition (BC) to determine the
      influence of forage environment on BW and BC changes, intramuscular fat
      percentage (IMF), rump fat (RF), and serum hormones during 2 yr. Cows within each
      BC were randomly assigned to graze either common bermudagrass (CB; n = 3
      pastures/yr) or toxic endophyte-infected tall fescue (EI; n = 3 pastures/yr)
      during a 60-d breeding season. Blood samples were collected at d 0, 30, and 60 of
      the breeding season, and serum concentrations of prolactin (PRL), IGF-I, and
      cortisol (CORT) were quantified; PRL and progesterone (P(4)) also were quantified
      10 d before the breeding season (d -10). Body weight and BCS were recorded during
      the breeding season (d 0, 30, and 60). Cow IMF and RF were measured via
      ultrasonography at the start and end of the breeding season. Cows with increased
      (>1 ng/mL) P(4) at the beginning of the breeding season (cyclic) had greater (P <
      0.02) concentrations of PRL on d 30 and 60 compared with anestrous cows. A forage
      environment * BC interaction tended (P = 0.07) to influence PRL. Cows grazing CB
      independent of BC had increased PRL compared with cows grazing EI. Prolactin was
      decreased in good-BC cows grazing EI compared with cows grazing CB, and cows in
      marginal BC grazing EI had the least concentrations of PRL. Concentrations of IGF
      I were similar (P > 0.10) among good- and marginal-BC cows grazing CB, as well as
      good-BC cows grazing EI; however, marginal-BC cows grazing EI had reduced (P <
      0.04) concentrations of IGF-I compared with all other groups. Cows in marginal BC
      grazing CB gained (P = 0.02) the most BW during the breeding season, whereas good
      BC cows grazing EI gained the least amount of BW. Marginal-BC cows grazing CB
      tended (P = 0.06) to increase BC during the breeding season, whereas good-BC cows
      grazing either CB or EI lost BC. Rump fat tended (P = 0.07) to increase during
      the breeding season in marginal-BC cows compared with cows in good BC. Calving
      rates were similar (P > 0.10) among good- (82%) and marginal- (84%) BC cows
      grazing CB, and good-BC cows grazing EI (79%); however, marginal-BC cows grazing
      EI had a reduced (P = 0.04) calving rate (61%). Cattle grazing EI during the
      breeding season lost BC. That reduction in BC may be communicated to the
      pituitary via hormones that include IGF-I or PRL or both, resulting in decreased
      calving rates.

PMID- 20817855
TI  - Association of liver abnormalities with carcass grading performance and value.
AB  - The association of liver abnormalities with carcass grading performance, value,
      and dressed yield was evaluated on data from 76,191 carcasses housed in 2
      databases. Liver abnormalities were assigned as follows: normal = edible liver; A
      = 1 to 2 small abscesses or inactive scars; A = 1 to 2 large abscesses or
      multiple small abscesses; A+ = multiple large abscesses; A+AD = liver adhered to
      gastrointestinal tract or diaphragm or both; A+OP = open liver abscess;
      cirrhosis; distoma; and telangiectasis. Overall liver abnormality rates among
      both databases were A- = 5.0%, A = 2.6%, A+ = 2.0%, A+AD = 2.7%, A+OP = 1.4%,
      cirrhosis = 0.1%, distoma = 5.4%, and telangiectasis = 0.3%, with 80.5% of livers
      being normal. In database 1 (n = 3,936), BW was 33.3 kg less (P < 0.01) for
      carcasses with cirrhotic livers compared with carcasses with normal livers.
      Dressed yields for carcasses with A-, A+, A+AD, A+OP, and cirrhosis liver
      abnormalities were 0.28 to 0.89 percentage points less (P < 0.05) than carcasses
      with normal livers. In database 2 (n = 72,255), carcasses with A-, A+, A+AD,
      A+OP, cirrhosis, distoma, and telangiectasis liver abnormalities had reduced (P <
      0.05) HCW and reduced (P < 0.05) LM area as compared with carcasses with a normal
      liver. Less (P < 0.05) 12th-rib subcutaneous fat was observed for carcasses with
      A-, A, A+, A+AD, A+OP, cirrhosis, and distoma abnormalities compared with
      carcasses with normal livers. Estimated KPH was less (P < 0.05) for carcasses
      with A-, A+, A+AD, A+OP, cirrhosis, and distoma abnormalities. Calculated yield
      grade was less (P < 0.05) for carcasses with A+AD, A+OP, cirrhosis, and distoma
      abnormalities compared with carcasses with normal livers. Marbling score of
      carcasses that had livers with A+AD or A+OP abscess scores or distoma was less (P
      < 0.05) than that of carcasses with normal livers. In database 2, market price
      per 45.35 kg did not differ (P = 0.32) among liver classification. Gross carcass
      value analyses indicated carcasses with A-, A, A+, A+AD, A+OP, cirrhosis, and
      distoma liver abnormalities were less valuable (P < 0.05) than carcasses with
      normal livers. These data delineate the association of liver abnormalities
      present at harvest with subsequent changes in carcass characteristics and
      ultimately lost carcass value.

PMID- 20817856
TI  - Feed efficiency differences and reranking in beef steers fed grower and finisher
      diets.
AB  - This 3-yr study used 490 steers to determine whether feedlot steers changed their
      feed efficiency (FE) ranking when fed a grower diet, then a finisher diet. The
      steers were crossbreds and were between 5 to 7 mo of age. There were 2 feeding
      periods each year. Within each year, approximately 90 steers had their diet
      switched from a grower to a finisher diet (feed-swap group), whereas another 90
      steers were fed either the grower (grower-fed group) or the finisher (finisher
      fed group) diet throughout the feeding trial. Each feeding test lasted for a
      minimum of 10 wk, and all steers were fed ad libitum. Individual animal feed
      intakes were collected using the GrowSafe feeding system, and BW were measured
      every 2 wk. Residual feed intake (RFI), G:F, and Kleiber ratio (KR) were computed
      at the end of each feeding period. For each measure of efficiency, animals were
      classified as low, medium, or high based on 0.5 SD from the mean. The majority of
      steers did not maintain the previous efficiency class in the second period.
      Approximately 58, 51, and 51% of steers in the feed-swap group, finisher-fed
      group, and the grower-fed group, respectively, changed their RFI measure by 0.5
      SD. A low rank correlation occurred in all test groups but was less in the feed
      swap group. Spearman rank correlations between the 2 feeding periods in the feed
      swap group were 0.33, 0.20, and 0.31 for RFI, G:F, and KR, respectively.
      Classifications based on G:F and KR showed that a greater number of steers (P <
      0.05) in the feed-swap group did not maintain their FE class from 1 feeding
      regimen to the other, whereas classification based on RFI did not show any
      difference (P > 0.05) between the proportions of individuals that changed or
      maintained their FE class. In the groups without a feed-swap, there was no
      difference (P > 0.05) in the proportion of steers that changed or maintained the
      same FE class for all FE measures. Our results suggest that diet type and feeding
      period affect the FE ranking in beef steers. A feedlot diet is ideal for
      evaluating the FE potential of steers for feedlot profitability; however, we
      suggest that tests involving less dense diets should be examined in an effort to
      understand the relationships between FE and feeder profitability.

PMID- 20817857
TI  - Season of testing and its effect on feed intake and efficiency in growing beef
      cattle.
AB  - This study sought to assess whether residual feed intake (RFI) calculated by
      regressing feed intake (DMI) on growth rate (ADG) and metabolic mid-BW in 3
      different ways led to similar estimates of genetic parameters and variance
      components for young growing cattle tested for feed intake in fall and winter
      seasons. A total of 378 beef steers in 5 cohorts were fed a typical high energy
      feedlot diet and had free-choice access to feed and water. Feed intake data were
      collected in fall or winter seasons. Climate data were obtained from the
      University of Alberta Kinsella meteorological station and Vikings AGCM station.
      Individual animal RFI was obtained by either fitting a regression model to each
      test group separately (RFI(C)), fitting a regression model to pooled data
      consisting of all cohorts but including test group as a fixed effect (RFI(O)), or
      fitting a regression to pooled data with test group as a fixed effect but within
      seasonal (fall-winter or winter-spring) groups (RFI(S)). Two animal models (M1
      and M2) that differed by the inclusion of fixed effects of test group or season,
      respectively, were used to evaluate RFI measurements. Feed intake was correlated
      with air temperature, relative humidity, solar radiation, and wind speed (-0.26,
      0.23, 0.30, -0.14 for fall-winter and 0.31, -0.04, 0.14, 0.16 for winter-spring,
      respectively), but the nature and magnitude of the correlations were different
      for the 2 seasons. Single trait direct heritability, model likelihood, direct
      genetic variance, and EBV accuracy estimates were greatest for RFI(C) and least
      for RFI(O) for both M1 and M2 models. A significant genetic correlation was also
      observed between RFI(O) and ADG, but not for RFI(C) and RFI(S). Including a
      season effect (M2) in the genetic evaluation of RFI(O) resulted in the smallest
      heritability, model LogL, EBV accuracy, and largest residual variance estimates.
      These results, though not conclusive, suggest a possible effect of seasonality on
      feed intake and thus feed efficiency.

PMID- 20817858
TI  - Fresh meat and further processing characteristics of ham muscles from finishing
      pigs fed ractopamine hydrochloride.
AB  - Ractopamine hydrochloride (RAC) has consistently led to an advantage in carcass
      cutting yields of finishing pigs and remains a common feed additive in US
      finishing pig diets. Less is known about the effect of RAC on further processing
      characteristics. Some researchers have reported advantages in ultimate pH of the
      LM in pigs fed RAC. If a greater ultimate pH was also observed in hams, the
      increased pH could affect further processing characteristics and lead to better
      protein interaction and improved textural properties. The objective of this
      experiment was to determine if RAC-fed pigs yielded hams with a greater ultimate
      pH, and if so, whether or not that advantage improves textural properties and
      water retention of further processed hams. Two hundred hams from barrows and
      gilts fed RAC or control diets were selected based on HCW. Hams were fabricated
      into 5 separate pieces to determine cutting yields, and 6 muscles were evaluated
      for ultimate pH. Hams were processed to make cured and smoked hams. Ractopamine
      increased cutting yields of the whole ham (P < 0.0001), inside (P < 0.01),
      outside (P < 0.01), and knuckle (P < 0.01) when expressed as a percentage of
      chilled side weight. Ultimate pH of the rectus femoris, vastus lateralis, and
      semitendinosus were all 0.06 pH units greater (P < 0.05), the biceps femoris was
      0.04 pH units greater (P = 0.02), and the semimembranosus and adductor muscles
      were 0.03 pH units greater in pigs fed 7.4 mg/kg of RAC when compared with
      control pigs. Cured hams from RAC-fed pigs were heavier at all stages of
      production. No differences were detected in binding strengths (P = 0.88) or
      protein fat-free values (P = 0.13) between RAC (9.06 kg and 20.37) and control
      hams (9.01 kg and 20.13). Ractopamine increased cutting yields, total weight of
      cured hams, and ultimate muscle pH. Ractopamine can be fed to pigs to achieve the
      desired growth characteristic advantages and cutting yields without affecting
      further processed ham characteristics.

PMID- 20817859
TI  - Effects of spray-dried animal plasma on serous and intestinal redox status and
      cytokines of neonatal piglets.
AB  - The study investigated the effects of dietary supplementation with spray-dried
      animal plasma (SDAP) on growth performance, intestinal morphology, as well as
      serum and intestinal cytokines and antioxidant indicators of artificially reared
      neonatal piglets. Three diets, 1) control (a fish meal basal diet), 2) SDAP
      (containing 10% SDAP), and 3) autoclaved SDAP (auSDAP; containing 10% auSDAP),
      were fed to 36 weaned piglets (3 d old), which were randomly allotted to 3
      groups. At 21 d of age, blood and intestinal mucosal samples were collected from
      all piglets after they were slaughtered. Compared with the control, both SDAP and
      auSDAP improved ADFI and duodenal villus height of piglets (P < 0.05), whereas
      SDAP increased ADG and duodenal villus height to crypt depth ratio (P < 0.05).
      Piglets fed SDAP and auSDAP had reduced malondialdehyde (MDA) content in mucosa
      (P < 0.05). The concentration of serum MDA was decreased and mucosal catalase
      (CAT) activities were increased in piglets fed SDAP diet than those fed the
      control diet (P < 0.05). In the mucosa, both SDAP and auSDAP decreased tumor
      necrosis factor alpha, IL-6, transforming growth factor beta, and soluble IL-2
      receptor contents (P < 0.05). Mucosal IL-1beta was decreased in SDAP compared
      with auSDAP and control groups (P < 0.05). The SDAP and control groups had
      increased mucosal IL-2 compared with auSDAP group (P < 0.05). The cytokines in
      serum were not affected by SDAP and auSDAP. The results indicate that both SDAP
      and auSDAP improved the growth performance of neonatal piglets, whereas the SDAP
      had a greater effect. The benefits of SDAP probably resulted from the promotion
      of the intestinal development, which were accompanied by the increased
      antioxidant capacity and the decreased production of inflammatory factors in the
      intestinal mucosa.

PMID- 20817860
TI  - Effects of selection for decreased residual feed intake on composition and
      quality of fresh pork.
AB  - The objectives of this study were to determine the extent to which selection for
      decreased residual feed intake (RFI) affects pork composition and quality. Pigs
      from the fifth generation of selection for decreased RFI (select) and a randomly
      selected line (control) were utilized. Two experiments were conducted. In Exp. 1,
      barrows (22.6 +/- 3.9 kg) from select and control lines were paired based on age
      and BW. The test was conducted in 8 replicates of pairs for the test period of 6
      wk. Calpastatin activity and myosin isoforms profile were determined on samples
      from the LM. Control barrows were heavier (59.1 vs. 55.0 kg; P < 0.01) at the end
      of the test period. Calpastatin activity was greater (P < 0.01) in LM of select
      barrows than control barrows. In Exp. 2, composition and quality of gilts (114
      kg) from control and select lines were determined. The model included fixed
      effects of line, slaughter date, melanocortin-4 receptor (MC4R) genotype, barn
      group, line * slaughter date, genotype * line interactions, a covariate of off
      test BW, and sire, pen, and litter fitted as random effects. The select line (n =
      80) had 0.043 kg less (P < 0.05) RFI per day than the control line (n = 89). Loin
      quality and composition were determined at 2 d postmortem. Desmin degradation was
      measured at 2 and 7 d postmortem. Purge, cook loss, sensory traits, and star
      probe texture were measured at 7 to 10 d postmortem on cooked chops. Residual
      correlations between RFI and composition and quality traits were calculated.
      Compared with the control line, carcasses from the select line tended to have
      less (P = 0.09) backfat, greater (P < 0.05) loin depth, and greater (P < 0.05)
      fat free lean. Loin chops from the select line had less (P < 0.01) intramuscular
      lipid content than loin chops from control line. Significant residual
      correlations between RFI and both tenderness (r = 0.24, P < 0.01) and star probe
      (r = -0.26, P < 0.01) were identified. Selection for decreased RFI has the
      potential to improve carcass composition with few effects on pH and water-holding
      capacity. However, decreased RFI could negatively affect tenderness and texture
      because of decreased lipid content and decreased postmortem protein degradation.

PMID- 20817862
TI  - Bile salts and obesity.

PMID- 20817861
TI  - Effect of dietary organic zinc, manganese, copper, and cobalt supplementation on
      milk production, follicular growth, embryo quality, and tissue mineral
      concentrations in dairy cows.
AB  - This study evaluated potential effects of organic trace mineral supplementation
      on reproductive measures in lactating dairy cows. Cows were blocked by breed and
      randomly assigned at dry-off to receive inorganic trace mineral supplementation
      (control; n = 32) or to have a portion of supplemental inorganic Zn, Cu, Mn, and
      Co replaced with an equivalent amount of the organic forms of these minerals
      (treatment; n = 31). Trace minerals were provided through control or treatment
      premixes fed at 100 g.cow(-1).d(-1). Premixes were fed to dry cows (range = 40 to
      72 d before calving) in 1.8 kg.cow(-1).d(-1) concentrate pellets through a
      computer feeder to provide 40, 26, 70, and 100% of supplemented Zn, Mn, Cu, and
      Co, respectively, and to lactating cows (range = 69 to 116 d after calving) in a
      total mixed ration to provide 22, 14, 40, and 100% of supplemented Zn, Mn, Cu,
      and Co, respectively. Treatment increased milk production at wk 14 (P = 0.047)
      postcalving, milk urea N content (P = 0.039), and BW loss from calving to 1 mo
      postcalving (P = 0.040), and decreased milk fat percentage (P = 0.045) and BCS (P
      = 0.048). Treatment tended to increase milk production at wk 13 (P = 0.089)
      postcalving and endometrial tissue concentrations of Fe (P = 0.070), BW at mo 1
      (P = 0.056), and milk protein percentage (P = 0.064). Treatment did not affect (P
      > 0.1) DMI, health events, first-wave follicular dynamics, first cycle luteal
      measures, embryo quality, liver trace mineral concentrations, or luteal trace
      mineral concentrations. Cows with a rectal temperature >=39 degrees C at the time
      of AI had a smaller percentage of fertilized entities (P < 0.001). However, of
      the entities that were fertilized, the percentage of viable embryos, embryo
      quality, accessory sperm number, and embryo cell number were not affected (P >
      0.1) by treatment. We conclude that replacing a portion of inorganic supplemental
      trace minerals with an equivalent amount of these organic trace minerals (Zn, Mn,
      Cu, and Co) increased milk production in mid-lactation, but did not affect
      postpartum follicular dynamics, embryo quality, or liver and luteal trace mineral
      concentrations.

PMID- 20817863
TI  - Group V secretory phospholipase A2 reveals its role in house dust mite-induced
      allergic pulmonary inflammation by regulation of dendritic cell function.
AB  - We have previously shown that group V secretory phospholipase A(2) (sPLA(2))
      regulates phagocytosis of zymosan and Candida albicans by a mechanism that
      depends on fusion of phagosomes with late endosomes in macrophages. In this
      study, we report that group V sPLA(2) (Pla2g5)-null mice exposed to an extract of
      house dust mite Dermatophagoides farinae had markedly reduced pulmonary
      inflammation and goblet cell metaplasia compared with wild-type (WT) mice. Pla2g5
      null mice had also impaired Th2-type adaptive immune responses to D. farinae
      compared with WT mice. Pla2g5-null bone marrow-derived dendritic cells (BMDCs)
      activated by D. farinae had delayed intracellular processing of allergen and
      impaired allergen-dependent maturation, a pattern recapitulated by the native
      lung DCs of D. farinae-challenged mice. Adoptively transferred D. farinae-loaded
      Pla2g5-null BMDCs were less able than D. farinae-loaded WT BMDCs to induce
      pulmonary inflammation and Th2 polarization in WT mice. However, Pla2g5-null
      recipients transferred with WT or Pla2g5-null D. farinae-loaded BMDCs exhibited
      significantly reduced local inflammatory responses to D. farinae, even though the
      transfer of WT BMDCs still induced an intact Th2 cytokine response in regional
      lymph nodes. Thus, the expression of group V sPLA(2) in APCs regulates Ag
      processing and maturation of DCs and contributes to pulmonary inflammation and
      immune response against D. farinae. Furthermore, an additional yet to be
      identified resident cell type is essential for the development of pulmonary
      inflammation, likely a cell in which group V sPLA(2) is upregulated by D.
      farinae, and whose function is also regulated by group V sPLA(2).

PMID- 20817864
TI  - B7h triggering inhibits umbilical vascular endothelial cell adhesiveness to tumor
      cell lines and polymorphonuclear cells.
AB  - Vascular endothelial cells (ECs) are key players in leukocyte recruitment into
      tissues and metastatic dissemination of tumor cells. ECs express B7h, which is
      the ligand of the ICOS T cell costimulatory molecule. The aim of this work was to
      assess the effect of B7h triggering by a soluble form of ICOS (ICOS-Fc) on the
      adhesion of colon carcinoma cell lines to HUVECs. We found that B7h triggering
      inhibited HUVEC adhesiveness to HT29 and DLD1 cells (by 50 and 35%, respectively)
      but not to HCT116 cells. The effect was dependent on the ICOS-Fc dose and was
      detectable as early as 30 min after treatment and was still present after 24 h.
      It was inhibited by soluble anti-ICOS reagents (mAb and B7h-Fc) and silencing of
      B7h on HUVECs, and it was not displayed by an F119S mutated form of ICOS-Fc that
      does not bind B7h. HUVEC treatment with ICOS-Fc did not modulate expression of
      adhesion molecules and cytokines, but it substantially downmodulated ERK
      phosphorylation induced by E-selectin triggering or osteopontin, which may
      influence HUVEC adhesiveness. Moreover, HUVEC treatment with ICOS-Fc also
      inhibited adhesion of polymorphonuclear cells and several tumor cell lines from
      different origins. Therefore, the B7h-ICOS interaction may modulate spreading of
      cancer metastases and recruitment of polymorphonuclear cells in inflammatory
      sites, which opens a view on the use of ICOS-Fc as an immunomodulatory drug.

PMID- 20817865
TI  - Conventional B2 B cell depletion ameliorates whereas its adoptive transfer
      aggravates atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory arterial disease characterized by focal
      accumulation of lipid and inflammatory cells. It is the number one cause of
      deaths in the Western world because of its complications of heart attacks and
      strokes. Statins are effective in only approximately one third of patients,
      underscoring the urgent need for additional therapies. B cells that accumulate in
      atherosclerotic lesions and the aortic adventitia of humans and mice are
      considered to protect against atherosclerosis development. Unexpectedly, we found
      that selective B cell depletion in apolipoprotein E-deficient (ApoE(-/-)) mice
      using a well-characterized mAb to mouse CD20 reduced atherosclerosis development
      and progression without affecting the hyperlipidemia imposed by a high-fat diet.
      Adoptive transfer of 5 * 10(6) or 5 * 10(7) conventional B2 B cells but not 5 *
      10(6) B1 B cells to a lymphocyte-deficient ApoE(-/-) Rag-2(-/-) common cytokine
      receptor gamma-chain-deficient mouse that was fed a high-fat diet augmented
      atherosclerosis by 72%. Transfer of 5 * 10(6) B2 B cells to an ApoE(-/-) mouse
      deficient only in B cells aggravated atherosclerosis by >300%. Our findings
      provide compelling evidence for the hitherto unrecognized proatherogenic role of
      conventional B2 cells. The data indicate that B2 cells can potently promote
      atherosclerosis development entirely on their own in the total absence of all
      other lymphocyte populations. Additionally, these B2 cells can also significantly
      augment atherosclerosis development in the presence of T cells and all other
      lymphocyte populations. Our findings raise the prospect of B cell depletion as a
      therapeutic approach to inhibit atherosclerosis development and progression in
      humans.

PMID- 20817866
TI  - Free Ig light chains interact with sphingomyelin and are found on the surface of
      myeloma plasma cells in an aggregated form.
AB  - Free kappa L chains (FkappaLCs) are expressed on the surface of myeloma cells and
      are being assessed as a therapeutic target for the treatment of multiple myeloma.
      Despite its clinical potential, the mechanism by which FkappaLCs interact with
      membranes remains unresolved. In this study, we show that FkappaLCs associate
      with sphingomyelin on the plasma membrane of myeloma cells. Moreover, membrane
      bound FkappaLCs are aggregated, suggesting that aggregation is required for
      intercalation with membranes. Finally, we propose a model where the binding of
      FkappaLCs with sphingomyelin on secretory vesicle membranes is stabilized by self
      aggregation, with aggregated FkappaLCs exposed on the plasma membrane after
      exocytosis. Although it is well known that protein aggregates bind membranes,
      this is only the second example of an aggregate being found on the surface of
      cells that also secrete the protein in its native form. We postulate that many
      other aggregation-prone proteins may associate with cell membranes by similar
      mechanisms.

PMID- 20817868
TI  - IL-27/IFN-gamma induce MyD88-dependent steroid-resistant airway
      hyperresponsiveness by inhibiting glucocorticoid signaling in macrophages.
AB  - Inflammation and airway hyperresponsiveness (AHR) are hallmark features of asthma
      and often correlate with the severity of clinical disease. Although these
      features of asthma can be effectively managed with glucocorticoid therapy, a
      subgroup of patients, typically with severe asthma, remains refractory to
      therapy. The mechanisms leading to steroid resistance in severe asthmatics are
      poorly understood but may be related to the activation of innate host defense
      pathways. Previously, we have shown that IFN-gamma-producing cells and LPS, two
      factors that are associated with severe asthma, induce steroid-resistant AHR in a
      mouse model. We now demonstrate that cooperative signaling induced by IFN-gamma
      and LPS results in the production of IL-27 by mouse pulmonary macrophages. IL-27
      and IFN-gamma uniquely cooperate to induce glucocorticoid-resistant AHR through a
      previously unknown MyD88-dependent mechanism in pulmonary macrophages.
      Importantly, integrated signaling by IL-27/IFN-gamma inhibits glucocorticoid
      induced translocation of the glucocorticoid receptor to the nucleus of
      macrophages. Furthermore, expression of both IL-27 and IFN-gamma was increased in
      the induced sputum of steroid-refractory asthmatics. These results suggest that a
      potential mechanism for steroid resistance in asthma is the activation of MyD88
      dependent pathways in macrophages that are triggered by IL-27 and IFN-gamma, and
      that manipulation of these pathways may be a therapeutic target.

PMID- 20817869
TI  - Identification of two IgD+ B cell populations in channel catfish, Ictalurus
      punctatus.
AB  - Channel catfish Ictalurus punctatus express two Ig isotypes: IgM and IgD.
      Although catfish IgM has been extensively studied at the functional and
      structural levels, much less is known about IgD. In this study, IgM(+)/IgD(+) and
      IgM(-)/IgD(+) catfish B cell populations were identified through the use of anti
      IgM and anti-IgD mAbs. Catfish IgM(+)/IgD(+) B cells are small and agranular. In
      contrast, IgM(-)/IgD(+) B cells are larger and exhibit a plasmablast morphology.
      The use of cell sorting, flow cytometry, and RT-PCR demonstrated that IgD(+) B
      cell expression varies among individuals. For example, some catfish have <5% IgM(
      )/IgD(+) B cells in their PBLs, whereas in others the IgM(-)/IgD(+) B cell
      population can represent as much as 72%. Furthermore, IgD expressed by IgM(
      )/IgD(+) B cells preferentially associates with IgL sigma. Comparatively,
      IgM(+)/IgD(+) B cells can express any of the four catfish IgL isotypes. Also,
      transfection studies show that IgD functions as a typical BCR, because Igdelta
      chains associate with CD79a and CD79b molecules, and all membrane IgD transcripts
      from sorted IgM(-)/IgD(+) B cells contain viable VDJ rearrangements, with no bias
      in family member usage. Interestingly, all secreted IgD transcripts from
      IgM(+)/IgD(+) and IgM(-)/IgD(+) B cells were V-less and began with a leader
      spliced to Cdelta1. Importantly, transfection of catfish clonal B cells
      demonstrated that this leader mediated IgD secretion. Together, these findings
      imply that catfish IgM(-)/IgD(+) B cells likely expand in response to certain
      pathogens and that the catfish IgD Fc-region, as has been suggested for human
      IgD, may function as a pattern recognition molecule.

PMID- 20817867
TI  - Regulation of the B cell receptor repertoire and self-reactivity by BAFF.
AB  - The TNF-family cytokine BAFF (BLyS) promotes B lymphocyte survival and is
      overexpressed in individuals with systemic lupus erythematosus and Sjogren's
      Syndrome. BAFF can rescue anergic autoreactive B cells from death, but only when
      competition from nonautoreactive B cells is lacking. Yet, high BAFF levels
      promote autoantibody formation in individuals possessing diverse B cells. To
      better understand how excess BAFF promotes autoimmunity in a polyclonal immune
      system, Ig L chain usage was analyzed in 3H9 site-directed IgH chain transgenic
      mice, whose B cells recognize DNA and chromatin when they express certain
      endogenous L chains. BAFF levels were manipulated in 3H9 mice by introducing
      transgenes expressing either BAFF or its natural inhibitor DeltaBAFF. B cells in
      BAFF/3H9 mice were elevated in number, used a broad L chain repertoire, including
      L chains generating high-affinity autoreactivity, and produced abundant
      autoantibodies. Comparison of spleen and lymph node B cells suggested that highly
      autoreactive B cells were expanded. By contrast, DeltaBAFF/3H9 mice had reduced B
      cell numbers with a repertoire similar to that of 3H9 mice, but lacking usage of
      a subset of Vkappa genes. The results show that limiting BAFF signaling only
      slightly selects against higher affinity autoreactive B cells, whereas its
      overexpression leads to broad tolerance escape and positive selection of
      autoreactive cells. The results have positive implications for the clinical use
      of BAFF-depleting therapy.

PMID- 20817870
TI  - Selective inhibition of the lectin pathway of complement with phage display
      selected peptides against mannose-binding lectin-associated serine protease
      (MASP)-1 and -2: significant contribution of MASP-1 to lectin pathway activation.
AB  - The complement system, an essential part of the innate immune system, can be
      activated through three distinct routes: the classical, the alternative, and the
      lectin pathways. The contribution of individual activation pathways to different
      biological processes can be assessed by using pathway-selective inhibitors. In
      this paper, we report lectin pathway-specific short peptide inhibitors developed
      by phage display against mannose-binding lectin-associated serine proteases
      (MASPs), MASP-1 and MASP-2. On the basis of the selected peptide sequences, two
      14-mer peptides, designated as sunflower MASP inhibitor (SFMI)-1 and SFMI-2, were
      produced and characterized. SFMI-1 inhibits both MASP-1 and MASP-2 with a K(I) of
      65 and 1030 nM, respectively, whereas SFMI-2 inhibits only MASP-2 with a K(I) of
      180 nM. Both peptides block the lectin pathway activation completely while
      leaving the classical and the alternative routes intact and fully functional,
      demonstrating that of all complement proteases only MASP-1 and/or MASP-2 are
      inhibited by these peptides. In a C4 deposition inhibitor assay using
      preactivated MASP-2, SFMI-2 is 10-fold more effective than SFMI-1 in accordance
      with the fact that SFMI-2 is a more potent inhibitor of MASP-2. Surprisingly,
      however, out of the two peptides, SFMI-1 is much more effective in preventing C3
      and C4 deposition when normal human serum containing zymogen MASPs is used. This
      suggests that MASP-1 has a crucial role in the initiation steps of lectin pathway
      activation most probably by activating MASP-2. Because the lectin pathway has
      been implicated in several life-threatening pathological states, these inhibitors
      should be considered as lead compounds toward developing lectin pathway blocking
      therapeutics.

PMID- 20817872
TI  - Central nervous system demyelinating disease protection by the human commensal
      Bacteroides fragilis depends on polysaccharide A expression.
AB  - The importance of gut commensal bacteria in maintaining immune homeostasis is
      increasingly understood. We recently described that alteration of the gut
      microflora can affect a population of Foxp3(+)T(reg) cells that regulate
      demyelination in experimental autoimmune encephalomyelitis (EAE), the
      experimental model of human multiple sclerosis. We now extend our previous
      observations on the role of commensal bacteria in CNS demyelination, and we
      demonstrate that Bacteroides fragilis producing a bacterial capsular
      polysaccharide Ag can protect against EAE. Recolonization with wild type B.
      fragilis maintained resistance to EAE, whereas reconstitution with polysaccharide
      A-deficient B. fragilis restored EAE susceptibility. Enhanced numbers of
      Foxp3(+)T(reg) cells in the cervical lymph nodes were observed after intestinal
      recolonization with either strain of B. fragilis. Ex vivo, CD4(+)T cells obtained
      from mice reconstituted with wild type B. fragilis had significantly enhanced
      rates of conversion into IL-10-producing Foxp3(+)T(reg) cells and offered greater
      protection against disease. Our results suggest an important role for commensal
      bacterial Ags, in particular B. fragilis expressing polysaccharide A, in
      protecting against CNS demyelination in EAE and perhaps human multiple sclerosis.

PMID- 20817871
TI  - Gene expression profiles in a rabbit model of systemic lupus erythematosus
      autoantibody production.
AB  - We previously reported the establishment of a rabbit (Oryctolagus cuniculus)
      model in which peptide immunization led to production of lupus-like
      autoantibodies including anti-Sm, -RNP, -SS-A, -SS-B, and -dsDNA characteristic
      of those produced in systemic lupus erythematosus (SLE) patients. Some neurologic
      symptoms in the form of seizures and nystagmus were observed. The animals used in
      the previous and in the current study were from a National Institute of Allergy
      and Infectious Diseases colony of rabbits that were pedigreed, Ig-allotype
      defined, but not inbred. Their genetic heterogeneity may correspond to that found
      among patients of a given ethnicity. We extended the information about this
      rabbit model by microarray-based expression profiling. We first demonstrated that
      human expression arrays could be used with rabbit RNA to yield information on
      molecular pathways. We then designed a study evaluating gene expression profiles
      in eight groups of control and treated rabbits (47 rabbits in total). Genes
      significantly upregulated in treated rabbits were associated with NK
      cytotoxicity, Ag presentation, leukocyte migration, cytokine activity, protein
      kinases, RNA spliceosomal ribonucleoproteins, intracellular signaling cascades,
      and glutamate receptor activity. These results link increased immune activation
      with upregulation of components associated with neurologic and anti-RNP
      responses, demonstrating the utility of the rabbit model to uncover biological
      pathways related to SLE-induced clinical symptoms, including neuropsychiatric
      lupus. Our finding of distinct gene expression patterns in rabbits that made anti
      dsDNA compared with those that only made other anti-nuclear Abs should be further
      investigated in subsets of SLE patients with different autoantibody profiles.

PMID- 20817873
TI  - Human decidual tissue contains differentiated CD8+ effector-memory T cells with
      unique properties.
AB  - During pregnancy, maternal lymphocytes at the fetal-maternal interface play a key
      role in the immune acceptance of the allogeneic fetus. Recently,
      CD4(+)CD25(bright) regulatory T cells have been shown to be concentrated in
      decidual tissue, where they are able to suppress fetus-specific and nonspecific
      immune responses. Decidual CD8(+) T cells are the main candidates to recognize
      and respond to fetal HLA-C at the fetal-maternal interface, but data on the
      characteristics of these cells are limited. In this study we examined the
      decidual and peripheral CD8(+) T cell pool for CD45RA, CCR7, CD28, and CD27
      expression, using nine-color flow cytometry. Our data demonstrate that decidual
      CD8(+) T cells mainly consist of differentiated CD45RA(-)CCR7(-) effector-memory
      (EM) cells, whereas unprimed CD45RA(+)CCR7(+) naive cells are almost absent.
      Compared with peripheral blood EM CD8(+) T cells, the decidual EM CD8(+) T cells
      display a significantly reduced expression of perforin and granzyme B, which was
      confirmed by immunohistochemistry of decidual tissue sections. Interestingly,
      quantitative PCR analysis demonstrates an increased perforin and granzyme B mRNA
      content in decidual EM CD8(+) T cells in comparison with peripheral blood EM
      CD8(+) T cells. The presence of high levels of perforin and granzyme B mRNA in
      decidual EM T cells suggests that decidual CD8(+) T cells pursue alternative
      means of EM cell differentiation that may include a blockade of perforin and
      granzyme B mRNA translation into functional perforin and granzyme B proteins.
      Regulation of decidual CD8(+) T cell differentiation may play a crucial role in
      maternal immune tolerance to the allogeneic fetus.

PMID- 20817874
TI  - IL-1beta-mediated signals preferentially drive conversion of regulatory T cells
      but not conventional T cells into IL-17-producing cells.
AB  - Regulatory T cells (Tregs) are committed to suppressive functions. Recently, it
      was proposed that Tregs could produce IL-17 under proinflammatory, polarizing
      conditions. We studied the role of Tregs on IL-17 production in the absence of
      exogenous cytokines and insults. Using in vitro and in vivo approaches, we
      determined that under neutral conditions, simultaneous activation of Tregs and
      naive CD4(+) conventional T cells in the presence of APCs resulted in conversion
      of Tregs into IL-17-producing cells, and endogenous IL-1beta was mandatory in
      this process. Mechanistic analysis revealed that the IL-1R1 was highly expressed
      on Tregs and that IL-1beta induced marked activation of p38 and JNK, which were
      involved in IL-17 production. These observations could have important
      implications on therapeutic strategies using Tregs.

PMID- 20817875
TI  - The agonists of formyl peptide receptors prevent development of severe sepsis
      after microbial infection.
AB  - Severe sepsis, a principal cause of death in intensive care units, occurs when
      host immune defenses fail to combat invading microbes. In this paper, we report
      that the administration of peptide agonists of formyl peptide receptors,
      including Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), protected against death by enhanced
      bactericidal activity and inhibition of vital organ inflammation and immune cell
      apoptosis in a cecal ligation and puncture (CLP) sepsis mouse model. The
      administration of WKYMVm also enhanced the production of type 1 (IFN-gamma and IL
      12) and type 17 (IL-17 and TGF-beta) cytokines in CLP mice. In contrast, the
      administration of WKYMVm inhibited the production of proinflammatory cytokines
      (TNF-alpha, IL-1beta, and IL-6) in the CLP mice. The therapeutic and bactericidal
      effects of WKYMVm were partly reversed in IFN-gamma-deficient mice, whereas
      target organ inflammation was not. Meanwhile, the therapeutic and anti
      inflammatory effects of WKYMVm were partly reversed in IL-17-deficient mice. In
      addition, the administration of WKYMVm also enhanced type 1 and type 17 Th cell
      responses in mice sensitized with LPS plus Ags. These results suggest that the
      agonists of formyl peptide receptors effectively prevent development of severe
      sepsis following microbial infection partly via augmentation of type 1 and type
      17 immune responses.

PMID- 20817876
TI  - NF-kappaB links CO2 sensing to innate immunity and inflammation in mammalian
      cells.
AB  - Molecular O(2) and CO(2) are the primary substrate and product of aerobic
      metabolism, respectively. Levels of these physiologic gases in the cell
      microenvironment vary dramatically both in health and in diseases, such as
      chronic inflammation, ischemia, and cancer, in which metabolism is significantly
      altered. The identification of the hypoxia-inducible factor led to the discovery
      of an ancient and direct link between tissue O(2) and gene transcription. In this
      study, we demonstrate that mammalian cells (mouse embryonic fibroblasts and
      others) also sense changes in local CO(2) levels, leading to altered gene
      expression via the NF-kappaB pathway. IKKalpha, a central regulatory component of
      NF-kappaB, rapidly and reversibly translocates to the nucleus in response to
      elevated CO(2). This response is independent of hypoxia-inducible factor
      hydroxylases, extracellular and intracellular pH, and pathways that mediate acute
      CO(2)-sensing in nematodes and flies and leads to attenuation of bacterial LPS
      induced gene expression. These results suggest the existence of a molecular CO(2)
      sensor in mammalian cells that is linked to the regulation of genes involved in
      innate immunity and inflammation.

PMID- 20817877
TI  - Limited role for lymphotoxin alpha in the host immune response to Mycobacterium
      tuberculosis.
AB  - The contribution of lymphotoxin (LT)alpha in the host immune response to virulent
      Mycobacterium tuberculosis and Mycobacterium bovis bacillus Calmette-Guerin
      infections was investigated. Despite their ability to induce Th1 cytokine, IFN
      gamma, and IL-12 pulmonary response, "conventional" LTalpha(-/-) mice succumb
      rapidly to virulent M. tuberculosis aerosol infection, with uncontrolled bacilli
      growth, defective granuloma formation, necrosis, and reduced pulmonary inducible
      NO synthase expression, similar to TNF(-/-) mice. Contributions from
      developmental lymphoid abnormalities in LTalpha(-/-) mice were excluded because
      hematopoietic reconstitution with conventional LTalpha(-/-) bone marrow conferred
      enhanced susceptibility to wild-type mice, comparable to conventional LTalpha(-/
      ) control mice. However, conventional LTalpha(-/-) mice produced reduced levels
      of TNF after M. bovis bacillus Calmette-Guerin infection, and their lack of
      control of mycobacterial infection could be due to a defective contribution of
      either LTalpha or TNF, or both, to the host immune response. To address this
      point, the response of "neo-free" LTalpha(-/-) mice with unperturbed intrinsic
      TNF expression to M. tuberculosis infection was investigated in a direct
      comparative study with conventional LTalpha(-/-) mice. Strikingly, although
      conventional LTalpha(-/-) mice were highly sensitive, similar to TNF(-/-) mice,
      neo-free LTalpha(-/-) mice controlled acute M. tuberculosis infection essentially
      as wild-type mice. Pulmonary bacterial burden and inflammation was, however,
      slightly increased in neo-free LTalpha(-/-) mice 4-5 mo postinfection, but
      importantly, they did not succumb to infection. Our findings revise the notion
      that LTalpha might have a critical role in host defense to acute mycobacterial
      infection, independent of TNF, but suggest a contribution of LTalpha in the
      control of chronic M. tuberculosis infection.

PMID- 20817878
TI  - A protein's conformational stability is an immunologically dominant factor:
      evidence that free-energy barriers for protein unfolding limit the immunogenicity
      of foreign proteins.
AB  - Foreign protein Ags are incorporated into APCs and then degraded by endosomal
      proteases. The peptides are then mounted on MHC II molecules on the surfaces of
      APCs. The T cell-triggering response and, therefore, the immune response, were
      suggested to be governed by the degree of conformational stability of the foreign
      protein Ags. However, there is little evidence that a protein's conformational
      stability is an immunologically dominant factor. In this study, we show that a
      protein has a threshold of conformational stability to prevent the immunogenicity
      of foreign proteins. Inverse and linear correlations were found between the
      amount of IgG production against lysozymes and the free-energy change for the
      unfolding of lysozymes, based on the correlation between the free-energy changes
      of the protein unfolding and the amount of IgG production against lysozymes with
      different stabilities in mice using hen egg white lysozyme derivatives and mutant
      mouse lysozymes, in which the sequence between 107 and 116 is replaced with that
      of hen egg white lysozyme, which can produce autoantibodies in mice.
      Interestingly, the thresholds of free-energy changes for both lysozymes to
      prevent their immunogenicity were almost identical (21-23 kcal/mol). To confirm
      the results, we also showed that the cross-linking of Phl p 7, in which intact
      Phl p 7 has stability greater than ~20 kcal/mol under physiological conditions,
      induced minimal IgG production in mice, whereas intact Phl p 7 was antigenic.
      From the above results, we suggest that protein conformational stability was an
      immunologically dominant factor.

PMID- 20817879
TI  - Cutting edge: Intrathymic differentiation of adaptive Foxp3+ regulatory T cells
      upon peripheral proinflammatory immunization.
AB  - Thymocytes differentiate into CD4(+) Foxp3(+) regulatory T cells (T(R)) upon
      interaction between their TCR and peptide-MHC II complexes locally expressed in
      the thymus. Conversion of naive CD4(+) T cells into T(R) can additionally take
      place in the periphery under noninflammatory conditions of Ag encounter. In this
      study, making use of TCR transgenic models naturally devoid of Foxp3(+) cells, we
      report de novo generation of T(R) upon a single footpad injection of Ag mixed
      with a classic proinflammatory adjuvant. Abrupt T(R) differentiation upon
      immunization occurred intrathymically and was essential for robust tolerance
      induction in a mouse model of spontaneous encephalomyelitis. This phenomenon
      could be attributed to a specific feature of thymocytes, which, in contrast to
      mature peripheral CD4(+) T cells, were insensitive to the inhibitory effects of
      IL-6 on the induction of Foxp3 expression. Our findings uncover a pathway for
      T(R) generation with major implications for immunity and tolerance induction.

PMID- 20817880
TI  - IRAK-M removal counteracts dendritic cell vaccine deficits in migration and
      longevity.
AB  - To function optimally as vaccines, dendritic cells (DCs) must actively migrate to
      lymphoid organs and maintain a viable, mature state for sufficient time to
      effectively present their Ag to cognate T cells. Unfortunately, mature DCs
      rapidly lose viability and function after injection, and only a minority leaves
      the vaccine site and migrates to lymph nodes. We show that all of these functions
      can be enhanced in DCs by removal of IL-1R-associated kinase M (IRAK-M). We found
      that IRAK-M is induced in DCs by TLR ligation and that its absence from these
      cells leads to increased activation of the p38-MAPK and NF-kappaB pathways,
      which, in turn, improves DC migration to lymph nodes, increases their longevity,
      and augments their secretion of Th1-skewing cytokines and chemokines. These
      biological effects have immunological consequences. IRAK-M(-/-) DCs increase the
      proliferation and activation of Ag-specific T cells, and a single vaccination
      with Ag-pulsed, LPS-matured IRAK-M(-/-) DCs eliminates established tumors and
      prolongs the survival of EG7 or B16.f10 tumor-bearing mice, without discernible
      induction of autoimmune disease. Thus, manipulation of IRAK-M levels can increase
      the potency of DC vaccines by enhancing their Ag-presenting function, migration,
      and longevity.

PMID- 20817881
TI  - Complement C3a, CpG oligos, and DNA/C3a complex stimulate IFN-alpha production in
      a receptor for advanced glycation end product-dependent manner.
AB  - The receptor for advanced glycation end products (RAGE) is a multiligand
      transmembrane receptor implicated in a number of diseases including autoimmune
      diseases. To further understand the pathogenic mechanism of RAGE in these
      diseases, we searched for additional ligands. We discovered that C3a bound to
      RAGE with an EC(50) of 1.9 nM in an ELISA, and the binding was increased both in
      magnitude (by >2-fold) and in affinity (EC(50) 70 pM) in the presence of human
      stimulatory unmethylated cytosine-guanine-rich DNA A (hCpGAs). Surface plasmon
      resonance and fluorescence anisotropy analyses demonstrated that hCpGAs could
      bind directly to RAGE and C3a and form a ternary complex. In human PBMCs, C3a
      increased IFN-alpha production in response to low levels of hCpGAs, and this
      synergy was blocked by soluble RAGE or by an Ab directed against RAGE. IFN-alpha
      production was reduced in response to mouse CpGAs and C3a in RAGE(-/-) mouse bone
      marrow cells compared wild-type mice. Taken together, these data demonstrate that
      RAGE is a receptor for C3a and CpGA. Through direct interaction, C3a and CpGA
      synergize to increase IFN-alpha production in a RAGE-dependent manner and
      stimulate an innate immune response. These findings indicate a potential role of
      RAGE in autoimmune diseases that show accumulation of immunostimulatory DNA and
      C3a.

PMID- 20817882
TI  - Pandemic H1N1 influenza A viruses are resistant to the antiviral activities of
      innate immune proteins of the collectin and pentraxin superfamilies.
AB  - Acquired immune responses elicited to recent strains of seasonal H1N1 influenza
      viruses provide limited protection against emerging A(H1N1) pandemic viruses.
      Accordingly, pre-existing or rapidly induced innate immune defenses are of
      critical importance in limiting early infection. Respiratory secretions contain
      proteins of the innate immune system, including members of the collectin and
      pentraxin superfamilies. These mediate potent antiviral activity and act as an
      initial barrier to influenza infection. In this study, we have examined the
      sensitivity of H1N1 viruses, including pandemic virus strains, for their
      sensitivity to collectins (surfactant protein [SP]-D and mannose-binding lectin
      [MBL]) and to the pentraxin PTX3. Human SP-D and MBL inhibited virus-induced
      hemagglutinating activity, blocked the enzymatic activity of the viral
      neuraminidase, and neutralized the ability of H1N1 viruses to infect human
      respiratory epithelial cells in a manner that correlated with the degree of
      glycosylation in the globular head of the hemagglutinin. Recent seasonal H1N1
      viruses expressed three to four N-glycosylation sequons on the head of
      hemagglutinin and were very sensitive to inhibition by SP-D or MBL, whereas
      A(H1N1) pandemic viruses expressed a single N-glycosylation sequon and were
      resistant to either collectin. Of interest, both seasonal and pandemic H1N1
      viruses were resistant to PTX3. Thus, unlike recent seasonal H1N1 strains of
      influenza virus, A(H1N1) pandemic viruses are resistant to the antiviral
      activities of innate immune proteins of the collectin superfamily.

PMID- 20817883
TI  - Muscular dystrophies: a way forward.

PMID- 20817884
TI  - Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet): case
      definition in surveillance for childhood-onset Duchenne/Becker muscular
      dystrophy.
AB  - The Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) is
      a multisite collaboration to determine the prevalence of childhood-onset
      Duchenne/Becker muscular dystrophy and to characterize health care and health
      outcomes in this population. MD STARnet uses medical record abstraction to
      identify patients with Duchenne/Becker muscular dystrophy born January 1, 1982 or
      later who resided in 1 of the participating sites. Critical diagnostic elements
      of each abstracted record are reviewed independently by >4 clinicians and
      assigned to 1 of 6 case definition categories (definite, probable, possible,
      asymptomatic, female, not Duchenne/Becker muscular dystrophy) by consensus. As of
      November 2009, 815 potential cases were reviewed. Of the cases included in
      analysis, 674 (82%) were either ''definite'' or ''probable'' Duchenne/Becker
      muscular dystrophy. These data reflect a change in diagnostic testing, as case
      assignment based on genetic testing increased from 67% in the oldest cohort (born
      1982-1987) to 94% in the cohort born 2004 to 2009.

PMID- 20817886
TI  - Target immobilization as a strategy for NMR-based fragment screening: comparison
      of TINS, STD, and SPR for fragment hit identification.
AB  - Fragment-based drug discovery (FBDD) has become a widely accepted tool that is
      complementary to high-throughput screening (HTS) in developing small-molecule
      inhibitors of pharmaceutical targets. Because a fragment campaign can only be as
      successful as the hit matter found, it is critical that the first stage of the
      process be optimized. Here the authors compare the 3 most commonly used methods
      for hit discovery in FBDD: high concentration screening (HCS), solution ligand
      observed nuclear magnetic resonance (NMR), and surface plasmon resonance (SPR).
      They selected the commonly used saturation transfer difference (STD) NMR
      spectroscopy and the proprietary target immobilized NMR screening (TINS) as
      representative of the array of possible NMR methods. Using a target typical of
      FBDD campaigns, the authors find that HCS and TINS are the most sensitive to weak
      interactions. They also find a good correlation between TINS and STD for tighter
      binding ligands, but the ability of STD to detect ligands with affinity weaker
      than 1 mM K(D) is limited. Similarly, they find that SPR detection is most suited
      to ligands that bind with K(D) better than 1 mM. However, the good correlation
      between SPR and potency in a bioassay makes this a good method for hit validation
      and characterization studies.

PMID- 20817887
TI  - Experimental design and statistical methods for improved hit detection in high
      throughput screening.
AB  - Identification of active compounds in high-throughput screening (HTS) contexts
      can be substantially improved by applying classical experimental design and
      statistical inference principles to all phases of HTS studies. The authors
      present both experimental and simulated data to illustrate how true-positive
      rates can be maximized without increasing false-positive rates by the following
      analytical process. First, the use of robust data preprocessing methods reduces
      unwanted variation by removing row, column, and plate biases. Second, replicate
      measurements allow estimation of the magnitude of the remaining random error and
      the use of formal statistical models to benchmark putative hits relative to what
      is expected by chance. Receiver Operating Characteristic (ROC) analyses revealed
      superior power for data preprocessed by a trimmed-mean polish method combined
      with the RVM t-test, particularly for small- to moderate-sized biological hits.

PMID- 20817888
TI  - Opportunistic bacterial infections in breeding colonies of the NSG mouse strain.
AB  - Spontaneous morbidity primarily affecting female breeders in 3 independent
      breeding colonies of NSG (NOD.Cg-Prkdc(scid) I12rg(tm1Wjl) /SzJ) mice prompted an
      investigation to uncover the cause of disease. Necropsies were performed on 264
      (157 female and 107 male) spontaneously sick, experimentally unmanipulated NSG
      mice. In sum, 42 mice (15.9%) had acute or chronic renal inflammatory lesions, of
      which 12 had concurrent histologic evidence of an ascending urinary tract
      infection. From 94 kidneys cultured for bacterial organisms, 23 (24.5%) grew
      Enterococcus sp and 19 (20.2%) grew Klebsiella oxytoca. Female mice were twice
      more likely than males to present with nephritis. These findings indicate that
      bacterial nephritis is a major contributor to morbidity in the NSG strain.

PMID- 20817889
TI  - Training pathologists in mouse pathology.
AB  - Expertise in the pathology of mice has expanded from traditional regulatory and
      drug safety screening (toxicologic pathology) primarily performed by veterinary
      pathologists to the highly specialized area of mouse research pathobiology
      performed by veterinary and medical pathologists encompassing phenotyping of
      mutant mice and analysis of research experiments exploiting inbred mouse strains
      and genetically engineered lines. With increasing use of genetically modified
      mice in research, mouse pathobiology and, by extension, expert mouse research
      oriented pathologists have become integral to the success of basic and
      translational biomedical research. Training for today's research-oriented mouse
      pathologist must go beyond knowledge of anatomic features of mice and strain
      specific background diseases to the specialized genetic nomenclature, husbandry,
      and genetics, including the methodology of genetic engineering and complex trait
      analysis. While training can be accomplished through apprenticeships in formal
      programs, these are often heavily service related and do not provide the
      necessary comprehensive training. Specialty courses and short-term mentoring with
      expert specialists are opportunities that, when combined with active practice and
      publication, will lead to acquisition of the skills required for cutting-edge
      mouse-based experimental science.

PMID- 20817890
TI  - Dental caries and caries-related periodontitis in type 2 diabetic mice.
AB  - Diabetic patients are predisposed to periodontal disease as well as dental
      caries; however, there are contradictory reports about the possible association
      between dental caries and diabetes. Thus, the authors set out to determine
      whether diabetes affects onset of dental caries and periodontal disease and to
      clarify whether dental caries and periodontal disease are associated with each
      other in diabetic db/db mice. Oral tissue was examined from 68 male mice
      (diabetic db/db and nondiabetic db/+; aged 20, 30, 40, and 50 weeks) and 20
      female mice (db/db and db/+; aged 50 weeks). Macroscopically, caries were seen
      developing in the diabetic mice by 20 weeks of age. The number of teeth with
      dental lesions increased with age in the db/db mice at a significantly higher
      incidence than that of db/+ mice. Histologically, dental caries were detected in
      30 of 120 molars in 17 of 20 db/db mice at 50 weeks of age and in 4 of 108 molars
      in 4 of 18 db/+ mice of the same age. The severity of dental caries in db/db mice
      was significantly higher than it was in db/+ mice. Dental caries were a primary
      change that led to bacterial gingivitis and pulpitis. These lesions spread to the
      dental root and periodontal connective tissue through the apical foramen. Apical
      periodontitis was more frequent and severe when occurring in close association
      with dental caries. In conclusion, there is a strong relationship between
      diabetes and dental caries, but in this model, it is highly probable that the
      onset of periodontal disease was a secondary change resulting from dental caries.

PMID- 20817891
TI  - Rats susceptible to virus-induced asthma have a persistent virus-induced change
      in the predominant pulmonary form of the NF-kappaB inhibitor IkappaBalpha.
AB  - Weanling Brown Norway (BN) rats are susceptible to persistent steroid-responsive
      pulmonary abnormalities following resolution of an acute respiratory virus
      infection. In contrast, Fischer 344 (F344) rats recover without complications.
      Previous studies determined that NF-kappaB activation and subunit composition
      were markedly different between these 2 rat strains. This study examined whether
      viral infection also resulted in altered pulmonary expression of IkappaBalpha and
      IkappaBbeta, 2 inhibitory regulators of NF-kappaB. Western blot analyses of total
      pulmonary protein extracted from BN and F344 rats at 7, 10, and 14 days after
      inoculation (n = 5 per group) did not reveal virus-induced differences in
      IkappaBbeta expression. In contrast, a lower molecular weight form of
      IkappaBalpha appeared in the BN rats at 14 days postinfection, and it was still
      present at 21 days after infection (n = 5 per group). The change in IkappaBalpha
      expression observed in the susceptible BN but not the resistant F344 animals
      occurs when the epithelium is proliferating during the repair phase, and it
      correlates with the development of the persistent virus-induced airway
      inflammation and pulmonary functional abnormalities. These results further
      implicate differential regulation of NF-kappaB in the pathogenesis of virus
      induced asthma.

PMID- 20817892
TI  - Sudden death associated with myocardial contraction band necrosis in Boer goat
      kids.
AB  - Parenteral selenium (Se) and vitamin E (Vit E) were administered to all newborn
      kids at a Boer goat farm where there was previous high neonatal mortality assumed
      to be due to nutritional myopathy. All treated kids were affected by severe
      respiratory distress and died within 8 hours of Se/Vit E administration. Gross
      lesions included severe pulmonary edema, hydrothorax, and hydropericardium. The
      primary histopathologic finding was severe, acute, and monophasic myocardial
      contraction band necrosis. The diagnosis was accidental acute selenosis based on
      trace mineral analysis of the liver. This case highlights an important
      differential diagnosis in cases of acute myocardial contraction band necrosis and
      sudden death in goats and emphasizes the need for caution when administering
      parenteral Se/Vit E preparations.

PMID- 20817893
TI  - Uterine lesions in 32 female miniature pet pigs.
AB  - Thirty-two 4-month-old to 19-year-old female miniature pet pigs were spayed.
      Uterine lesions were present in all except 8 pigs. The 24 remaining pigs had
      diffuse cystic endometrial hyperplasia, of which 14 had smooth muscle tumors,
      including leiomyomas and leiomyosarcomas, in the uterus or broad ligament.
      Nodular endometrial lesions-including adenocarcinomas, adenomas, and/or
      adenomyosis-were present in 10 pigs, 3 of which had concurrent smooth muscle
      tumors. Pyometra was present in 3 pigs. In uterine sections with cystic
      endometrial hyperplasia, adenomyosis, or adenomas, approximately 70% of
      epithelial nuclei expressed estrogen receptor and progesterone receptor
      immunohistochemically; in adenocarcinomas, expression was 20%. Regardless of
      malignancy, more than 50% of nuclei in smooth muscle tumors expressed estrogen
      receptor and progesterone receptor. Aging was associated with the development of
      uterine lesions in miniature pet pigs.

PMID- 20817894
TI  - Efficient and cost-effective extraction of genomic DNA from formalin-fixed and
      paraffin-embedded tissues.
AB  - Diagnostic and investigative molecular pathology frequently has to resort to
      extraction of DNA from formalin-fixed and paraffin-embedded tissue samples.
      Although many different protocols are reported for this type of material,
      extraction of sufficient amounts of intact DNA is still challenging. Here, the
      authors report a reproducible, simple, cost-effective, and efficient protocol
      that yields up to 140 MUg of DNA from approximately 10 to 15 mg of formalin-fixed
      and paraffin-embedded tissue samples and compare it to available protocols. The
      protocol allows stable amplification of DNA fragments up to 600 bp in length in a
      wide variety of tissues.

PMID- 20817895
TI  - What is the outlook for equine practice?

PMID- 20817896
TI  - Severity and outcome of equine pasture-associated laminitis managed in first
      opinion practice in the UK.
AB  - Data from 107 cases of pasture-associated laminitis were obtained from first
      opinion practices to study factors associated with severity, survival and return
      to ridden exercise. There were 43 mares and 64 geldings, with a median age of 11
      years. Of the 107 animals, 33 were small ponies, 45 were large ponies/cobs, 17
      were small horses and 12 were large horses. Ninety-seven animals were categorised
      as having laminitis as defined by Cripps and Eustace (1999): 76 had mild (Obel
      grade 1 or 2) laminitis and 31 had severe (Obel grade 3 or 4) laminitis. Forty
      three animals had previously had laminitis, and were significantly less likely
      (P=0.02) to have severe laminitis than those that had not. Eighty-nine animals
      were overweight, and there was a trend (P=0.09) towards severe laminitis cases
      having a higher body mass index. Eight weeks after disease onset, 102 animals
      were alive. Lower bodyweight, optimal body condition, mild laminitis and category
      of acute/chronic founder as defined by Cripps and Eustace (1999) were
      significantly associated with survival. There was a trend (P=0.06) towards
      treatment with acepromazine being associated with survival. Of the 81 animals
      that were used for riding, 48 were being ridden again; this was 2.6 times more
      likely in animals without previous laminitis. The clinical outcome was judged by
      a panel of three veterinarians as 'good' in 77 of 107 of cases. Clinical outcome
      was significantly associated (P=0.03) with horse type: the outcome was 'bad' in
      none of the small horses, compared with 15 of 45 large ponies/cobs, 11 of 33
      small ponies and three of 12 large horses.

PMID- 20817897
TI  - Modifications of some acute phase proteins and the white blood cell count in
      thoroughbreds during training.
AB  - The concentrations of plasma fibrinogen and serum haptoglobin and the white blood
      cell count (WBC) were assessed in 17 thoroughbreds. All horses were trained for
      80 days, six days a week, with one day of rest per week. Blood samples were
      collected from each animal by jugular venepuncture, at 06.00, every 20 days for a
      period of 80 days, and the fibrinogen and haptoglobin concentrations and WBC were
      determined. One-way repeated measures analysis of variance, followed by the
      Bonferroni test, was used to determine significant differences. Training was
      associated with a significant increase in the concentrations of plasma fibrinogen
      (P<0.01) and serum haptoglobin (P<0.0005), but had no significant effect on the
      WBC count.

PMID- 20817898
TI  - Mitomycin C, with or without surgery, for the treatment of ocular squamous cell
      carcinoma in horses.
AB  - Ocular lesions in horses, confirmed as squamous cell carcinoma, were treated
      topically with mitomycin C. Fourteen horses with confirmed ocular squamous cell
      carcinoma, three of which were affected bilaterally, were included in the study.
      Eight of the affected eyes were treated topically with mitomycin C alone; in the
      other nine eyes, the tumours were surgically removed and topical treatment with
      mitomycin C was then applied. The treatment protocol consisted of 0.2 ml of 0.04
      per cent mitomycin C instilled into the conjunctival sac of the affected eye,
      every six hours, in rounds of seven days of treatment followed by seven days
      without treatment. This was repeated until full regression of the tumour occurred
      (up to four rounds of treatment with mitomycin C). Of the eight eyes treated with
      mitomycin C alone (without surgery), clinical resolution occurred in six cases.
      Of the nine eyes treated with a combination of surgery and topical mitomycin C,
      clinical resolution occurred in seven cases. No complications were observed.

PMID- 20817899
TI  - Prevalence of equine herpesvirus type 1 in trigeminal ganglia and submandibular
      lymph nodes of equids examined postmortem.
AB  - The objective of this study was to detect and characterise the biovar of equine
      herpesvirus type 1 (EHV-1) from submandibular lymph nodes (SMLNs) and trigeminal
      ganglia from 153 equids undergoing routine postmortem examination for various
      medical and surgical reasons. A combination of nucleic acid precipitation and
      preamplification steps was used to increase the analytical sensitivity of the
      analysis. The presence of latent EHV-1 was determined when tissue samples were
      PCR-positive for the glycoprotein B (gB) gene and the DNA polymerase (ORF 30)
      gene of EHV-1 in the absence of detectable late structural protein gene (gB gene)
      mRNA. The SMLNs of five of the study animals (3.3 per cent) were PCR-positive for
      the gB gene of EHV-1. Two SMLNs carried a latent neurotropic strain of the virus,
      whereas three SMLNs were PCR-positive for both neurotropic and non-neurotropic
      EHV-1. A total of 30 trigeminal ganglia collected from 19 horses were PCR
      positive for the gB gene of EHV-1. Nine trigeminal ganglia harboured either
      latent non-neurotropic or neurotropic EHV-1 strains. Twelve trigeminal ganglia
      contained both latent neurotropic and non-neurotropic EHV-1. The prevalence and
      distribution of EHV-1 biovars among the study horses appeared to be influenced by
      their breed and the type of tissue tested.

PMID- 20817900
TI  - West Nile virus serosurveillance in horses in Donana, Spain, 2005 to 2008.

PMID- 20817901
TI  - Equine degenerative myeloencephalopathy in a horse in the UK.

PMID- 20817902
TI  - Equine influenza viruses isolated during outbreaks in China in 2007 and 2008.

PMID- 20817906
TI  - Reporting of injection-site sarcomas in cats.

PMID- 20817907
TI  - Increase in maedi-visna breakdowns.

PMID- 20817909
TI  - Unusual proximal metaphyseal-diaphyseal tibial fracture in skeletally immature
      dogs.

PMID- 20817910
TI  - Tailspike interactions with lipopolysaccharide effect DNA ejection from phage P22
      particles in vitro.
AB  - Initial attachment of bacteriophage P22 to the Salmonella host cell is known to
      be mediated by interactions between lipopolysaccharide (LPS) and the phage
      tailspike proteins (TSP), but the events that subsequently lead to DNA injection
      into the bacterium are unknown. We used the binding of a fluorescent dye and DNA
      accessibility to DNase and restriction enzymes to analyze DNA ejection from phage
      particles in vitro. Ejection was specifically triggered by aggregates of purified
      Salmonella LPS but not by LPS with different O-antigen structure, by lipid A,
      phospholipids, or soluble O-antigen polysaccharide. This suggests that P22 does
      not use a secondary receptor at the bacterial outer membrane surface. Using phage
      particles reconstituted with purified mutant TSP in vitro, we found that the
      endorhamnosidase activity of TSP degrading the O-antigen polysaccharide was
      required prior to DNA ejection in vitro and DNA replication in vivo. If, however,
      LPS was pre-digested with soluble TSP, it was no longer able to trigger DNA
      ejection, even though it still contained five O-antigen oligosaccharide repeats.
      Together with known data on the structure of LPS and phage P22, our results
      suggest a molecular model. In this model, tailspikes position the phage particles
      on the outer membrane surface for DNA ejection. They force gp26, the central
      needle and plug protein of the phage tail machine, through the core
      oligosaccharide layer and into the hydrophobic portion of the outer membrane,
      leading to refolding of the gp26 lazo-domain, release of the plug, and ejection
      of DNA and pilot proteins.

PMID- 20817911
TI  - Missing the forest for the trees: object-discrimination learning blocks
      categorization learning.
AB  - Growing evidence indicates that error-driven associative learning underlies the
      ability of nonhuman animals to categorize natural images. This study explored
      whether this form of learning might also be at play when people categorize
      natural objects in photographs. Two groups of college students (a blocking group
      and a control group) were trained on a categorization task and then tested with
      novel photographs from each category; however, only the blocking group received
      pretraining on a task that required the discrimination of objects from the same
      category. Because of this earlier noncategorical discrimination learning, the
      blocking group performed well in the categorization task from the outset, and
      this strong initial performance reduced the likelihood of category learning
      driven by error. There was far less transfer of categorical responding during
      testing in the blocking group than in the control group; this finding suggests
      that learning the specific properties of each photographic image in pretraining
      blocked later learning of an open-ended category.

PMID- 20817912
TI  - Overheard cell-phone conversations: when less speech is more distracting.
AB  - Why are people more irritated by nearby cell-phone conversations than by
      conversations between two people who are physically present? Overhearing someone
      on a cell phone means hearing only half of a conversation--a "halfalogue." We
      show that merely overhearing a halfalogue results in decreased performance on
      cognitive tasks designed to reflect the attentional demands of daily activities.
      By contrast, overhearing both sides of a cell-phone conversation or a monologue
      does not result in decreased performance. This may be because the content of a
      halfalogue is less predictable than both sides of a conversation. In a second
      experiment, we controlled for differences in acoustic factors between these types
      of overheard speech, establishing that it is the unpredictable informational
      content of halfalogues that results in distraction. Thus, we provide a cognitive
      explanation for why overheard cell-phone conversations are especially irritating:
      Less-predictable speech results in more distraction for a listener engaged in
      other tasks.

PMID- 20817913
TI  - Relational mobility explains between- and within-culture differences in self
      disclosure to close friends.
AB  - In the current research, we tested a novel explanation for previously
      demonstrated findings that East Asians disclose less personal information to
      other people than do Westerners. We propose that both between- and within-culture
      differences in self-disclosure to close friends may be explained by the construct
      of relational mobility, the general degree to which individuals in a society have
      opportunities to form new relationships and terminate old ones. In Study 1, we
      found that cross-cultural differences (Japan vs. United States) in self
      disclosure to a close friend were mediated by individuals' perceptions of
      relational mobility. In Study 2, two separate measures of relational mobility
      predicted self-disclosure within a single culture (Japan), and this relationship
      was mediated by the motivation to engage in self-disclosure to strengthen
      personal relationships. We conclude that societies and social contexts higher in
      relational mobility (in which relationships can be formed and dissolved
      relatively easily) produce stronger incentives for self-disclosure as a social
      commitment device.

PMID- 20817914
TI  - Spatial resolution of conscious visual perception in infants.
AB  - Humans' conscious awareness of objects in their visual periphery is limited. This
      limit is not entirely the result of reduced visual acuity. Rather, it is
      primarily caused by crowding--the difficulty identifying an object when it is
      surrounded by clutter. The effect of crowding on visual awareness in infants has
      yet to be explored. Do infants, for example, have a fine-grained "spotlight," as
      adults do, or do infants have a diffuse "lantern" that sets limits on what they
      can register in their visual periphery? We designed an eye-tracking paradigm to
      psychophysically measure crowding in infants between 6 months and 15 months of
      age. We showed infants pairs of faces at three eccentricities, in the presence or
      absence of flankers, and recorded infants' first saccade from central fixation to
      either face. Infants could discriminate faces in the periphery, and flankers
      impaired this ability. We found that the effective spatial resolution of infants'
      visual perception increased with age, but was only half that of adults.

PMID- 20817916
TI  - Neuroscience: viable applications in education?
AB  - As a relatively young science, neuroscience is still finding its feet in
      potential collaborations with other disciplines. One such discipline is
      education, with the field of neuroeducation being on the horizon since the 1960s.
      However, although its achievements are now growing, the partnership has not been
      as successful as first hopes suggested it should be. Here the authors discuss the
      theoretical barriers and potential solutions to this, which have been suggested
      previously, with particular focus on levels of research in neuroscience and their
      applicability to education. Moreover, they propose that these theoretical
      barriers are driven and maintained by practical barriers surrounding common
      language and research literacy. They propose that by overcoming these practical
      barriers through appropriate training and shared experience, neuroeducation can
      reach its full potential.

PMID- 20817917
TI  - Human cortical control of hand movements: parietofrontal networks for reaching,
      grasping, and pointing.
AB  - In primates, control of the limb depends on many cortical areas. Whereas
      specialized parietofrontal circuits have been proposed for different movements in
      macaques, functional neuroimaging in humans has revealed widespread, overlapping
      activations for hand and eye movements and for movements such as reaching and
      grasping. This review examines the involvement of frontal and parietal areas in
      hand and arm movements in humans as revealed with functional neuroimaging. The
      degree of functional specialization, possible homologies with macaque cortical
      regions, and differences between frontal and posterior parietal areas are
      discussed, as well as a possible organization of hand movements with respect to
      different spatial reference frames. The available evidence supports a cortical
      organization along gradients of sensory (visual to somatosensory) and effector
      (eye to hand) preferences.

PMID- 20817918
TI  - Inflammation in neurological disorders: a help or a hindrance?
AB  - Inflammation of the central nervous system (CNS) (neuroinflammation) is now
      recognized to be a feature of all neurological disorders. In multiple sclerosis,
      there is prominent infiltration of various leukocyte subsets into the CNS. Even
      when there is no significant inflammatory infiltrates, such as in Parkinson or
      Alzheimer disease, there is intense activation of microglia with resultant
      elevation of many inflammatory mediators within the CNS. An extensive dataset
      describes neuroinflammation to have detrimental consequences, but results
      emerging largely over the past decade have indicated that aspects of the
      inflammatory response are beneficial for CNS outcomes. Benefits of
      neuroinflammation now include neuroprotection, the mobilization of neural
      precursors for repair, remyelination, and even axonal regeneration. The findings
      that neuroinflammation can be beneficial should not be surprising as a properly
      directed inflammatory response in other tissues is a natural healing process
      after an insult. In this article, we review the data that highlight the dual
      aspects of neuroinflammation in being a hindrance on the one hand but also a
      significant help for recovery of the CNS on the other. We consider how the
      inflammatory response may be beneficial or injurious, and we describe strategies
      to harness the beneficial aspects of neuroinflammation.

PMID- 20817919
TI  - Go or stop? Divergent roles of Reelin in radial neuronal migration.
AB  - Neuronal migration is an essential step of brain development and is controlled by
      a variety of cellular proteins and extracellular matrix molecules. Reelin, an
      extracellular matrix protein, is required for neuronal migration. Over the past
      10 years, the Reelin signaling cascade has been studied intensively. However, the
      role of Reelin in neuronal migration has remained unclear. Different Reelin
      fragments and different Reelin receptors suggest multiple functions of Reelin. In
      this review, the authors focus on Reelin effects on the actin cytoskeleton of
      migrating neurons.

PMID- 20817920
TI  - Nitric oxide signaling in brain function, dysfunction, and dementia.
AB  - Nitric oxide (NO) is an important signaling molecule that is widely used in the
      nervous system. With recognition of its roles in synaptic plasticity (long-term
      potentiation, LTP; long-term depression, LTD) and elucidation of calcium
      dependent, NMDAR-mediated activation of neuronal nitric oxide synthase (nNOS),
      numerous molecular and pharmacological tools have been used to explore the
      physiology and pathological consequences for nitrergic signaling. In this review,
      the authors summarize the current understanding of this subtle signaling pathway,
      discuss the evidence for nitrergic modulation of ion channels and homeostatic
      modulation of intrinsic excitability, and speculate about the pathological
      consequences of spillover between different nitrergic compartments in
      contributing to aberrant signaling in neurodegenerative disorders. Accumulating
      evidence points to various ion channels and particularly voltage-gated potassium
      channels as signaling targets, whereby NO mediates activity-dependent control of
      intrinsic neuronal excitability; such changes could underlie broader mechanisms
      of synaptic plasticity across neuronal networks. In addition, the inability to
      constrain NO diffusion suggests that spillover from endothelium (eNOS) and/or
      immune compartments (iNOS) into the nervous system provides potential
      pathological sources of NO and where control failure in these other systems could
      have broader neurological implications. Abnormal NO signaling could therefore
      contribute to a variety of neurodegenerative pathologies such as
      stroke/excitotoxicity, Alzheimer's disease, multiple sclerosis, and Parkinson's
      disease.

PMID- 20817921
TI  - CRASH syndrome: does it teach us about neurotrophic functions of cell adhesion
      molecules?
AB  - L1 cell adhesion molecule is a transmembrane glycoprotein of the immunoglobulin
      superfamily. L1 plays essential roles in normal development of the nervous
      system, and the mutations in the L1 gene are responsible for CRASH syndrome, a
      very rare inherited disorder characterized by corpus callosum hypoplasia, mental
      retardation, adducted thumbs, spastic paraplegia, and hydrocephalus. Here it is
      hypothesized that in the normal nervous system, the synthesis and neurotrophic
      function of L1 is controlled by a positive feedback loop, which consists of L1,
      L1 sheddases, gamma-secretase, L1 extracellular domain (L1ED), L1 cytoplasmic
      domain (L1CD), and transcriptional factor Pax6. The mutations in L1ED or L1CD
      will disrupt this feedback loop and inhibit the synthesis and neurotrophic
      function of L1, therefore contributing to the severe phenotypes in CRASH
      syndrome. Supported by several lines of experimental evidence, this hypothesis
      has important implications for the therapy of CRASH syndrome by guiding the
      development of novel strategies to restore this positive feedback loop to recover
      the normal function of L1 in CRASH patients.

PMID- 20817922
TI  - Specific HIV-1 integrase polymorphisms change their prevalence in untreated
      versus antiretroviral-treated HIV-1-infected patients, all naive to integrase
      inhibitors.
AB  - OBJECTIVES: To define whether the prevalence of mutations associated with
      integrase inhibitor (INI) resistance is different in untreated versus
      antiretroviral-treated HIV-1-infected individuals (all INI naive). METHODS: Gene
      sequences of the integrase (IN) and reverse transcriptase (RT) obtained from
      plasma samples of a well-defined cohort of 448 HIV-1-infected individuals (134
      drug naive and 314 antiretroviral treated) were analysed. Docking simulations,
      using RT and IN models, were also performed. RESULTS: Primary mutations and the
      majority of secondary mutations for raltegravir or elvitegravir were completely
      absent (or rarely found, <1%) in INI-naive patients, either drug naive or
      antiretroviral treated. Specific IN polymorphisms increased their frequency in
      antiretroviral-treated patients, and showed positive associations with specific
      RT resistance mutations. M154I and V165I IN polymorphisms occurred at a frequency
      of 6% in untreated patients, reaching 21.3% and 13.4%, respectively, in
      antiretroviral-treated patients. The mutation M154L, absent in drug-naive
      patients, was prevalent at 5.7% in antiretroviral-treated patients, and was
      positively associated with RT resistance mutations F227L and T215Y. Similarly,
      V165I and G163R mutations were associated with the RT resistance mutations F227L
      and M230L, respectively, and the T206S polymorphism was associated with the RT
      resistance mutation L210W. Docking simulations showed several favourable contacts
      between IN and RT residues. CONCLUSIONS: Overall, results confirm that primary
      and secondary INI-associated mutations are absent or extremely rare in INI-naive
      patients. Conversely, a few specific IN polymorphisms found in INI-naive patients
      increased their frequency in antiretroviral-failing patients and/or are
      associated with RT resistance mutations. The potential contribution of such
      polymorphisms to the evolution of resistance under the pressure of INIs needs
      further investigation.

PMID- 20817923
TI  - Neuropathology of epilepsy and psychosis: the contributions of J.A.N. Corsellis.
AB  - Professor J.A.N. Corsellis, whose life and work is recalled here, gained great
      insight into the meaning of morphological cerebral aberrations found in
      neuropsychiatric disease through exact neuropathological investigations of tissue
      specimens obtained from patients with distinct syndromes. He was a leading
      authority in the field. We have searched and compiled resources relating to
      J.A.N. Corsellis' life and work, including personal memories from colleagues and
      data from scientific publications. J.A.N. Corsellis made seminal contributions to
      the understanding of neuropsychiatric disease; his works substantially added to
      the understanding of the dementias, schizophrenia and the psychoses, and
      morphological sequelae of boxing. In seizure disorders, his name is linked to the
      first description of focal cortical dysplasia and limbic encephalitis, the
      pathology of status epilepticus and Ammon's horn sclerosis, and the systematic
      investigation of epilepsy surgery specimens in general. Both his life and work
      are closely linked to Runwell Hospital, Wickford, Essex and the Maudsley
      Hospital. During his professional life he established a large brain bank, now
      known as the Corsellis Collection. J.A.N. Corsellis had significant impact on
      neuroscience; many of his observations were groundbreaking and are still valid.

PMID- 20817924
TI  - Mutations in C16orf57 and normal-length telomeres unify a subset of patients with
      dyskeratosis congenita, poikiloderma with neutropenia and Rothmund-Thomson
      syndrome.
AB  - Dyskeratosis congenita (DC) is an inherited poikiloderma which in addition to the
      skin abnormalities is typically associated with nail dystrophy, leucoplakia, bone
      marrow failure, cancer predisposition and other features. Approximately 50% of DC
      patients remain genetically uncharacterized. All the DC genes identified to date
      are important in telomere maintenance. To determine the genetic basis of the
      remaining cases of DC, we undertook linkage analysis in 20 families and
      identified a common candidate gene region on chromosome 16 in a subset of these.
      This region included the C16orf57 gene recently identified to be mutated in
      poikiloderma with neutropenia (PN), an inherited poikiloderma displaying
      significant clinical overlap with DC. Analysis of the C16orf57 gene in our
      uncharacterized DC patients revealed homozygous mutations in 6 of 132 families.
      In addition, three of six families previously classified as Rothmund-Thomson
      syndrome (RTS-a poikiloderma that is sometimes confused with PN) were also found
      to have homozygous C16orf57 mutations. Given the role of the previous DC genes in
      telomere maintenance, telomere length was analysed in these patients and found to
      be comparable to age-matched controls. These findings suggest that mutations in
      C16orf57 unify a distinct set of families which clinically can be categorized as
      DC, PN or RTS. This study also highlights the multi-system nature (wider than
      just poikiloderma and neutropenia) of the clinical features of affected
      individuals (and therefore house-keeping function of C16orf57), a possible role
      for C16orf57 in apoptosis, as well as a distinct difference from previously
      characterized DC patients because telomere length was normal.

PMID- 20817926
TI  - BRCC36A is epistatic to BRCA1 in DNA crosslink repair and homologous
      recombination in Arabidopsis thaliana.
AB  - BRCA1 is a well-known tumor suppressor protein in mammals, involved in multiple
      cellular processes such as DNA repair, chromosome segregation and chromatin
      remodeling. Interestingly, homologs of BRCA1 and several of its complex partners
      are also found in plants. As the respective mutants are viable, in contrast to
      mammalian mutants, detailed analyses of their biological role is possible. Here
      we demonstrate that the model plant Arabidopsis thaliana harbors two homologs of
      the mammalian BRCA1 interaction partner BRCC36, AtBRCC36A and AtBRCC36B. Mutants
      of both genes as well as the double mutants are fully fertile and show no defects
      in development. We were able to show that mutation of one of the homologs,
      AtBRCC36A, leads to a severe defect in intra- and interchromosomal homologous
      recombination (HR). A HR defect is also apparent in Atbrca1 mutants. As the
      Atbrcc36a/Atbrca1 double mutant behaves like the single mutants of AtBRCA1 and
      AtBRCC36A both proteins seem to be involved in a common pathway in the regulation
      of HR. AtBRCC36 is also epistatic to AtBRCA1 in DNA crosslink repair. Upon
      genotoxic stress, AtBRCC36A is transferred into the nucleus.

PMID- 20817925
TI  - Kinesin-1 transport reductions enhance human tau hyperphosphorylation,
      aggregation and neurodegeneration in animal models of tauopathies.
AB  - Neurodegeneration induced by abnormal hyperphosphorylation and aggregation of the
      microtubule-associated protein tau defines neurodegenerative tauopathies.
      Destabilization of microtubules by loss of tau function and filament formation by
      toxic gain of function are two mechanisms suggested for how abnormal tau triggers
      neuronal loss. Recent experiments in kinesin-1 deficient mice suggested that
      axonal transport defects can initiate biochemical changes that induce activation
      of axonal stress kinase pathways leading to abnormal tau hyperphosphorylation.
      Here we show using Drosophila and mouse models of tauopathies that reductions in
      axonal transport can exacerbate human tau protein hyperphosphorylation, formation
      of insoluble aggregates and tau-dependent neurodegeneration. Together with
      previous work, our results suggest that non-lethal reductions in axonal
      transport, and perhaps other types of minor axonal stress, are sufficient to
      induce and/or accelerate abnormal tau behavior characteristic of Alzheimer's
      disease and other neurodegenerative tauopathies.

PMID- 20817927
TI  - Characterization of SMG-9, an essential component of the nonsense-mediated mRNA
      decay SMG1C complex.
AB  - SMG-9 is part of a protein kinase complex, SMG1C, which consists of the SMG-1
      kinase, SMG-8 and SMG-9. SMG1C mediated phosphorylation of Upf1 triggers nonsense
      mediated mRNA decay (NMD), a eukaryotic surveillance pathway that detects and
      targets for degradation mRNAs harboring premature translation termination codons.
      Here, we have characterized SMG-9, showing that it comprises an N-terminal 180
      residue intrinsically disordered region (IDR) followed by a well-folded C
      terminal domain. Both domains are required for SMG-1 binding and the integrity of
      the SMG1C complex, whereas the C-terminus is sufficient to interact with SMG-8.
      In addition, we have found that SMG-9 assembles in vivo into SMG-9:SMG-9 and,
      most likely, SMG-8:SMG-9 complexes that are not constituents of SMG1C. SMG-9 self
      association is driven by interactions between the C-terminal domains and
      surprisingly, some SMG-9 oligomers are completely devoid of SMG-1 and SMG-8. We
      propose that SMG-9 has biological functions beyond SMG1C, as part of distinct SMG
      9-containing complexes. Some of these complexes may function as intermediates
      potentially regulating SMG1C assembly, tuning the activity of SMG-1 with the NMD
      machinery. The structural malleability of IDRs could facilitate the transit of
      SMG-9 through several macromolecular complexes.

PMID- 20817928
TI  - Visualizing RAD51-mediated joint molecules: implications for recombination
      mechanism and the effect of sequence heterology.
AB  - The defining event in homologous recombination is the exchange of base-paired
      partners between a single-stranded (ss) DNA and a homologous duplex driven by
      recombinase proteins, such as human RAD51. To understand the mechanism of this
      essential genome maintenance event, we analyzed the structure of RAD51-DNA
      complexes representing strand exchange intermediates at nanometer resolution by
      scanning force microscopy. Joint molecules were formed between substrates with a
      defined ssDNA segment and homologous region on a double-stranded (ds) partner. We
      discovered and quantified several notable architectural features of RAD51 joint
      molecules. Each end of the RAD51-bound joints had a distinct structure. Using
      linear substrates, a 10-nt region of mispaired bases blocked extension of joint
      molecules in all examples observed, whereas 4 nt of heterology only partially
      blocked joint molecule extension. Joint molecules, including 10 nt of heterology,
      had paired DNA on either side of the heterologous substitution, indicating that
      pairing could initiate from the free 3'end of ssDNA or from a region adjacent to
      the ss-ds junction. RAD51 filaments covering joint ss-dsDNA regions were more
      stable to disassembly than filaments covering dsDNA. We discuss how distinct
      structural features of RAD51-bound DNA joints can play important roles as
      recognition sites for proteins that facilitate and control strand exchange.

PMID- 20817929
TI  - PCAF interacts with XBP-1S and mediates XBP-1S-dependent transcription.
AB  - X-box binding protein 1 (XBP-1) is a key regulator required for cellular unfolded
      protein response (UPR) and plasma cell differentiation. In addition, involvement
      of XBP-1 in host cell-virus interaction and transcriptional regulation of
      viruses, such as human T-lymphotropic virus type 1 (HTLV-1), has been revealed
      recently. Two XBP-1 isoforms, XBP-1U and XBP-1S, which share an identical N
      terminal domain, are present in cells. XBP-1S is a transcription activator while
      XBP-1U is the inactive isoform. Although the transactivation domain of XBP-1S has
      been identified within the XBP-1S-specific C-terminus, molecular mechanism of the
      transcriptional activation by XBP-1S still remains unknown. Here we report the
      interaction between p300/CBP-associated factor (PCAF) and XBP-1S through the C
      terminal domain of XBP-1S. No binding between XBP-1U and PCAF is detected. In a
      cell-based reporter assay, overexpression of PCAF further stimulates the XBP-1S
      mediated cellular and HTLV-1 transcription while knockdown of PCAF exhibits the
      opposite effect. Expression of endogenous XBP-1S cellular target genes, such as
      BiP and CHOP, is significantly inhibited when PCAF is knocked down. Furthermore,
      PCAF is recruited to the promoters of XBP-1S target genes in vivo, in a XBP-1S
      dependent manner. Collectively, our results demonstrate that PCAF mediates the
      XBP-1S-dependent transcription through the interaction with XBP-1S.

PMID- 20817930
TI  - Health selection operating between classes and across employment statuses.
AB  - BACKGROUNDS: The debate on health selection which describes the influence of
      health on subsequent social mobility is highly contested. The authors set out to
      examine the effect of health selection by looking at the effect of previous
      health status on changes in socio-economic position (SEP) over two time periods.
      METHOD: Data were pooled from 13 waves (1991-2003) of the British Household Panel
      Survey (BHPS). Using a multilevel multinomial approach, the presence of health
      selection between classes and into/out of employment was concurrently tested and
      compared. RESULTS: In the descriptive analysis, poor health was consistently
      associated with moving downward, while the outcome was inverse for upward
      movement. After accounting for the data structure using multilevel analysis,
      health was a predictor for social mobility when leaving and entering employment,
      but the effect was minimal for transitions between classes for both men and
      women. CONCLUSION: The non-significant impact of health on mobility inside
      employment may reflect the presence of the significant impact of health on
      mobility between employment and non-employment. This implies that the effect of
      health was not evenly spread over all social mobility, but rather tends to
      concentrate on some types of mobility. The effect of each predictor on social
      mobility is more concentrated among specific transitions, and health and age were
      likely to be substantial in moving into/out of the labour force, whereas
      education was a relevant predictor for mobility into/out of upper classes, in
      particular, classes I/II.

PMID- 20817931
TI  - FK228 induces mitotic catastrophe in A549 cells by mistargeting chromosomal
      passenger complex localization through changing centromeric H3K9 hypoacetylation.
AB  - Previous studies have shown that histone deacetylase inhibitors (HDACis) can kill
      cancer cells. In addition, HDACis can induce mitotic catastrophe in cancer cells
      due to insufficient localization of chromosomal passenger complex (CPC) to the
      centromere. However, the mechanisms behind these phenomena remain unclear. In
      this study, we found that a HDACi, FK228, affected multiple epigenetic
      modification characteristics of the centromere, including enhanced acetylation of
      histone H3 lysine 9 (H3K9), decreased trimethylation of H3K9, and decreased
      phosphorylation of histone H3 serine 10 (H3S10) and centromere protein A (CENP
      A). These epigenetic changes implied that H3K9 hyperacetylation inhibits the CPC
      recruitment, induces impaired centromere assembly and function, and eventually
      leads to aberrant mitosis. These data suggested that hypoacetylation of histone
      in the pericentromere is the most important landmark for recruiting CPC and
      leading to the mitotic catastrophe in HDACi-induced killing of cancer cells.

PMID- 20817932
TI  - The oldest old and GP end-of-life care in the Dutch community: a nationwide
      study.
AB  - BACKGROUND: Provision of adequate care for the oldest old is increasingly
      crucial, given the current ageing trends. This study explores differences in end
      of-life care of the oldest (>=85 years) versus the younger (65-84 years) old;
      testing the hypothesis that age could be an independent correlate of receiving
      specialised palliative care services (SPCS), having palliative-centred treatment
      and dying in a preferred place. METHODS: general practitioners (GPs)
      participating in the nation-wide representative network in the Netherlands were
      asked to fill in patient, illness and care characteristics of all registered
      patients >=65 years, who died non-suddenly in their practices between 2005 and
      2008, using standardised forms. Associations with the palliative care variables
      were tested using multiple logistic regression. RESULTS: nine hundred and ninety
      patients were registered. Among the oldest old, there were more women than men,
      more patients with heart failure than cancer, less hospital and home deaths and
      more residential care home deaths compared with the younger old. Of the oldest
      old, fewer received SPCS and more preferred to die in a residential care home
      than the younger old. Age was independently associated with palliative care
      provided: compared with the younger group, the oldest old received SPCS less
      often (OR = 0.7) and were treated with a palliative-centred goal more often (OR =
      2.4); but age was not related to dying in a preferred place, i.e. independent of
      other characteristics. CONCLUSION: this study shows age to be independently
      associated with receiving SPCS in the Dutch community. Although the GPs do
      recognise the 'palliative phase' in the oldest old, involvement of specialist
      teams is somewhat less.

PMID- 20817933
TI  - Myoclonus and delirium associated with ciprofloxacin.

PMID- 20817934
TI  - Effects of height loss on morbidity and mortality in 3145 community-dwelling
      Chinese older women and men: a 5-year prospective study.
AB  - BACKGROUND: height loss beginning in mid-life and post-menopausal period was
      associated with adverse health outcomes. However, height loss occurring after old
      age has been little studied. We examined how height loss was related to bone
      mineral density (BMD) change, fracture incidence and cause-specific mortality in
      older adults. METHODS: the stature and BMD of 3145 community-dwelling men and
      women aged >=65 were measured at baseline and after 4 years. All fracture and
      cause-specific mortality events were searched in a territory-wide clinical
      information database and death registry. RESULTS: twenty-five (1.6%) men and 64
      (4.0%) women lost >2 cm after 4 years. In women, the BMD decline was faster in
      the rapid height losers (adjusted difference = 4.18%, P < 0.001). There was no
      corresponding difference observed in men. Rapid height loss was associated with
      excess all fractures and hip fractures (adjusted HR for all fractures = 2.86, P <
      0.001; adjusted HR for hip fractures = 4.74, P < 0.01) in women but only hip
      fractures (adjusted HR = 4.93, P < 0.05) in men. The all-cause (adjusted HR =
      3.43, P < 0.01) and respiratory disease mortality (adjusted HR = 5.64, P < 0.05)
      were higher in men with rapid height loss, whereas those in women were
      insignificant. CONCLUSIONS: modest height loss occurring after old age, >2 cm in
      4 years, was associated with excess hip fracture, total and respiratory disease
      mortality in older men. In women, it was associated with excess BMD decline, all
      fractures and hip fractures but not mortality. Further research is needed to
      determine the usefulness of regular stature measurement as an indicator of bone
      health in the primary-care setting in older adults.

PMID- 20817935
TI  - Leukocyte telomere length and marital status among middle-aged adults.
AB  - BACKGROUND: being unmarried is associated with worse health and increased
      mortality risk. Telomere length has emerged as a marker for biological ageing but
      it is unclear how telomere length relates to marital status. OBJECTIVE: to
      examine the relationship between telomere length and marital status in a sample
      of middle-aged adults. DESIGN AND SUBJECTS: cross-sectional analysis among 321
      adults aged 40-64 years. METHODS: telomere length was measured by PCR (T/S
      ratio). Participants provided information on healthy lifestyle activities
      including smoking, alcohol use, diet, exercise, obesity as well as social
      support. RESULTS: participants married or living with a partner had a mean T/S
      ratio of 1.70 and those widowed, divorced, separated or never married had a mean
      T/S ratio of 1.58 in a model adjusted for age, gender and race/ethnicity (P <
      0.001). When the analysis was further adjusted for diet, alcohol consumption,
      exercise, smoking, social support, poverty and obesity, persons married or living
      with a partner had a higher mean T/S ratio of 1.69 than their unmarried
      counterparts (1.59) (P = 0.004). CONCLUSIONS: these results indicate that
      unmarried individuals have shorter telomeres. This relationship between marital
      status and telomere length is independent of presumed benefits of marriage such
      as social support and a healthier lifestyle.

PMID- 20817936
TI  - The Whitehorse NoFalls trial: effects on fall rates and injurious fall rates.
AB  - BACKGROUND: the burden of falls and fall-related injuries among older adults is
      well established. Contention surrounds the effectiveness, and hence value, of
      multi-component fall prevention interventions delivered in the community.
      OBJECTIVE: using consensus-based analytic guidelines rather than time-to-first
      fall as the primary endpoint, the objective was to examine the effectiveness of
      the Whitehorse NoFalls trial on all falls, falls resulting in injury and falls
      requiring medical care to be sought. DESIGN, SETTING AND PARTICIPANTS: the study
      was a community-based randomised controlled trial, with 1,090 participants
      assigned to one of eight groups, these being a combination of one or more of
      exercise, vision and or home hazard reduction or alternatively assignment to the
      control group. METHODS: using negative binomial regression, the incidence of all
      falls, falls resulting in injury and those requiring medical care in the
      intervention groups were examined. Falls were reported using a monthly return
      calendar. RESULTS: exercise alone and in combination with vision and/or home
      hazard reduction was associated with fewer falls. For falls resulting in injury
      and the subset requiring medical care, the vision plus exercise intervention was
      associated with fewer falls. CONCLUSIONS: the findings confirm the effectiveness
      of exercise in preventing falls among community-dwelling older adults and
      supports contention that multi-component interventions do not prevent more falls
      than a single intervention. The results highlight the effectiveness of vision
      plus exercise in preventing more serious falls, a finding which warrants further
      consideration.

PMID- 20817937
TI  - Specialist medication review does not benefit short-term outcomes and net costs
      in continuing-care patients.
AB  - OBJECTIVES: to evaluate specialist geriatric input and medication review in
      patients in high-dependency continuing care. DESIGN: prospective, randomised,
      controlled trial. SETTING: two residential continuing care hospitals.
      PARTICIPANTS: two hundred and twenty-five permanent patients. INTERVENTION:
      patients were randomised to either specialist geriatric input or regular input.
      The specialist group had a medical assessment by a geriatrician and medication
      review by a multidisciplinary expert panel. Regular input consisted of review as
      required by a medical officer attached to each ward. Reassessment occurred after
      6 months. RESULTS: one hundred and ten patients were randomised to specialist
      input and 115 to regular input. These were comparable for age, gender, dependency
      levels and cognition. After 6 months, the total number of medications per patient
      per day fell from 11.64 to 11.09 in the specialist group (P = 0.0364) and
      increased from 11.07 to 11.5 in the regular group (P = 0.094). There was no
      significant difference in mortality or frequency of acute hospital transfers (11
      versus 6 in the specialist versus regular group, P = 0.213). CONCLUSION:
      specialist geriatric assessment and medication review in hospital continuing care
      resulted in a reduction in medication use, but at a significant cost. No benefits
      in hard clinical outcomes were demonstrated. However, qualitative benefits and
      lower costs may become evident over longer periods.

PMID- 20817938
TI  - Does the 'Otago exercise programme' reduce mortality and falls in older adults?:
      a systematic review and meta-analysis.
AB  - BACKGROUND: the 'Otago exercise programme' (OEP) is a strength and balance
      retraining programme designed to prevent falls in older people living in the
      community. The aim of this review was to evaluate the effect of the OEP on the
      risk of death and fall rates and to explore levels of compliance with the OEP in
      older adults. METHODS: a systematic review with meta-analysis. Clinical trials
      where the OEP was the primary intervention and participants were community
      dwelling older adults (65+) were included. Outcomes of interest included risk of
      death, number of falls, number of injurious falls and compliance to the exercise
      programme. RESULTS: seven trials, involving 1503 participants were included. The
      mean age of participants was 81.6 (+/-3.9) years. The OEP significantly reduced
      the risk of death over 12 months [risk ratio = 0.45, 95% confidence interval (CI)
      = 0.25-0.80], and significantly reduced fall rates (incidence rate ratio = 0.68,
      95% CI = 0.56-0.79). There was no significant difference in the risk of a serious
      or moderate injury occurring as the result of a fall (risk ratio = 1.05, 95% CI =
      0.91-1.22). Of the 747 participants who remained in the studies at 12 months, 274
      (36.7%) were still exercising three or more times per week. CONCLUSION: the OEP
      significantly reduces the risk of death and falling in older community-dwelling
      adults.

PMID- 20817939
TI  - Incessant ventricular tachycardia due to spontaneous automaticity in the Purkinje
      network inducing reversible left ventricular dysfunction.

PMID- 20817940
TI  - Sedation of children in the emergency department for short painful procedures
      compared with theatre, how much does it save? Economic evaluation.
AB  - INTRODUCTION: Sedation of children for short painful procedures is increasingly
      performed in emergency departments as an alternative to hospital admission and
      theatre. In this study, the savings of this are sought to be quantified. METHODS:
      A matched-cohort economic evaluation was conducted. Detailed case note reviews
      were performed on children who were sedated in the emergency department and
      children who were admitted to theatre. The costs of these were compared. RESULTS:
      17 children underwent sedation in our emergency department and were compared with
      20 children admitted to theatre. Each emergency department sedation saved L614
      (95% CI L441 to L787), and this result was statistically significant (p<0.0001).
      CONCLUSION: Emergency department sedation offers considerable savings, compared
      with theatre-based management for children who require short painful procedures.

PMID- 20817941
TI  - First return to work following injury: does it reflect a composite or a
      homogeneous outcome?
AB  - OBJECTIVE: To test whether return to work as a binary (yes/no) outcome that
      includes all persons who returned to work regardless of mode of return reflects a
      composite or a homogeneous outcome in a cohort of workers who have sustained
      acute orthopaedic trauma resulting in hospitalisation. METHODS: Prospective
      cohort study. One hundred and sixty-eight participants were recruited and
      followed for 6 months. The study achieved 89% follow-up. Baseline data were
      obtained at study recruitment and participants were further surveyed by phone at
      three timepoints during the study. Polytomous logistic regression was used to
      simultaneously examine the association between potential predictors and different
      modes of first return to work (RTW). A test of the equality of the ORs associated
      with the independent predictor variables was also undertaken. RESULTS: Of the 152
      participants with full follow-up, 46 (30%) returned first to full duties, 58
      (38%) returned first to modified work and 48 (32%) did not return to work during
      the study period. Significant determinants of the two modes of return to work
      were different. A test of the equality of ORs indicated that the relative ORs for
      the difference in the slope coefficients for five of the 10 independent factors
      in the two polytomous logistic regression sub-models corresponding to each mode
      of return to work were statistically significant. This raises the likelihood that
      first RTW reflects a composite rather than a homogeneous outcome. CONCLUSION: The
      study provides evidence that RTW may reflect a composite outcome when it includes
      different modes of first RTW. The identified predictive factors appear to exert
      different mechanisms of action depending on the mode of RTW. The findings suggest
      that the different modes of RTW may need to be considered independently. The
      results of the study have potentially important implications for research and
      insurance practice.

PMID- 20817942
TI  - Exposures in painting-related occupations and risk of lung cancer among men:
      results from two case-control studies in Montreal.
AB  - BACKGROUND: Evidence that painters may be at risk for lung cancer comes mainly
      from analyses on job titles rather than on specific exposures found in the
      environments of painters. METHODS: In the context of two large population-based
      case-control studies of lung cancer carried out in Montreal, we were able to
      assess possible relationships between lung cancer and the occupation of painter
      as well as exposure to paints, varnishes and stains. Interviews for study I were
      conducted in 1979-1986 (857 cases, 533 population controls, 1349 cancer controls)
      and interviews for study II were conducted in 1996-2001 (765 cases and 899
      controls). Detailed lifetime job histories were elicited; a team of hygienists
      and chemists evaluated the evidence of exposure to many occupational substances
      including paint-related substances. The relative risk of lung cancer was
      estimated, adjusting for several potential confounders, including smoking, in a
      three-variable parameterisation. RESULTS: In analyses pooling the two studies,
      painters had an OR of lung cancer of 1.3 (95% CI 0.9 to 2.2). Regarding
      exposures, ORs were: for wood varnishes and stains, 1.6 (95% CI 1.0 to 2.3); for
      wood and gypsum paints, 1.3 (95% CI 0.9 to 1.7); and for metal coatings, 1.1 (95%
      CI 0.8 to 1.6). Small numbers hampered evaluation of dose-response relationships.
      CONCLUSIONS: While our results cannot exclude chance or residual confounding by
      smoking or concomitant occupational exposures, they provide further evidence that
      some exposures in paint-related occupations, most notably wood varnishes and
      stains, increase the risk of lung cancer.

PMID- 20817943
TI  - Shifts in the intensity of purifying selection: an analysis of genome-wide
      polymorphism data from two closely related yeast species.
AB  - How much does the intensity of purifying selection vary among populations and
      species? How uniform are the shifts in selective pressures across the genome? To
      address these questions, we took advantage of a recent, whole-genome polymorphism
      data set from two closely related species of yeast, Saccharomyces cerevisiae and
      S. paradoxus, paying close attention to the population structure within these
      species. We found that the average intensity of purifying selection on amino acid
      sites varies markedly among populations and between species. As expected in the
      presence of extensive weakly deleterious mutations, the effect of purifying
      selection is substantially weaker on single nucleotide polymorphisms (SNPs)
      segregating within populations than on SNPs fixed between population samples.
      Also in accordance with a Nearly Neutral model, the variation in the intensity of
      purifying selection across populations corresponds almost perfectly to simple
      measures of their effective size. As a first step toward understanding the
      processes generating these patterns, we sought to tease apart the relative
      importance of systematic, genome-wide changes in the efficacy of selection, such
      as those expected from demographic processes and of gene-specific changes, which
      may be expected after a shift in selective pressures. For that purpose, we
      developed a new model for the evolution of purifying selection between
      populations and inferred its parameters from the genome-wide data using a
      likelihood approach. We found that most, but not all changes seem to be explained
      by systematic shifts in the efficacy of selection. One population, the sake
      derived strains of S. cerevisiae, however, also shows extensive gene-specific
      changes, plausibly associated with domestication. These findings have important
      implications for our understanding of purifying selection as well as for
      estimates of the rate of molecular adaptation in yeast and in other species.

PMID- 20817945
TI  - Why the xanthine derivatives are used to study of P-glycoprotein-mediated
      multidrug resistance in L1210/VCR line cells.
AB  - There is generally well known that various xanthines occur frequently in natural
      products, e.g. black coffee, black tea, green tea, natural dyes etc. Xanthine
      molecules are good tolerated and metabolised by organisms. Moreover, natural
      xanthines and/or sythesized xanthines may recall a lot positive affects
      (hemorheologic properties, anti-inflammatory properties, tracheal smooth muscle
      relaxant, positive chronotropic and central nervous system-stimulating, etc.) and
      may even induce a quantity of changes on the molecular level (inhibition of
      cyclic nucleotide phosphodiesterases, inhibition of the synthesis of tumor
      necrosis factor (TNF-alpha), cellular Ca(2+) homeostasis, etc.). In our previous
      paper we showed that some xanthine derivatives (pentoxifylline and its
      derivatives) depress P-glycoprotein (P-gp) mediated multidrug resistance of the
      mouse leukemic cells. Other authors, first of all Sadzuka and co-workers, confirm
      this usefulness of long side substituted xanthines as biochemical modulators.
      However, the mechanism of molecular action of xanthine derivatives has not been
      clarified. One of the possible ways to chemosensitize the cancer cells is direct
      competiting in defence mechanism - inhibition of efflux pump (P-gp). Interaction
      of xanthine derivatives with binding site of P-gp is a question which could be
      solved by experiment; although, molecular modelling may clear up this matter.
      But, each dynamic and static program for molecular simulation of P-gp action is
      dividing on input variable, considering mechanistic view of insight drug
      transport.

PMID- 20817944
TI  - p47phox Phox homology domain regulates plasma membrane but not phagosome
      neutrophil NADPH oxidase activation.
AB  - The assembly of cytosolic subunits p47(phox), p67(phox), and p40(phox) with
      flavocytochrome b(558) at the membrane is required for activating the neutrophil
      NADPH oxidase that generates superoxide for microbial killing. The p47(phox)
      subunit plays a critical role in oxidase assembly. Recent studies showed that the
      p47(phox) Phox homology (PX) domain mediates phosphoinositide binding in vitro
      and regulates phorbol ester-induced NADPH oxidase activity in a K562 myeloid cell
      model. Because the importance of the p47(phox) PX domain in neutrophils is
      unclear, we investigated its role using p47(phox) knock-out (KO) mouse
      neutrophils to express human p47(phox) and derivatives harboring R90A mutations
      in the PX domain that result in loss of phosphoinositide binding. Human p47(phox)
      proteins were expressed at levels similar to endogenous murine p47(phox), with
      the exception of a chronic granulomatous disease-associated R42Q mutant that was
      poorly expressed, and wild type human p47(phox) rescued p47(phox) KO mouse
      neutrophil NADPH oxidase activity. Plasma membrane NAPDH oxidase activity was
      reduced in neutrophils expressing p47(phox) with Arg(90) substitutions, with
      substantial effects on responses to either phorbol ester or formyl-Met-Leu-Phe
      and more modest effects to particulate stimuli. In contrast, p47(phox) Arg(90)
      mutants supported normal levels of intracellular NADPH oxidase activity during
      phagocytosis of a variety of particles and were recruited to phagosome membranes.
      This study defines a differential and agonist-dependent role of the p47(phox) PX
      domain for neutrophil NADPH oxidase activation.

PMID- 20817946
TI  - Hypoxia causes connexin 43 internalization in neonatal rat ventricular myocytes.
AB  - Gap junctions produce low resistance pathways between cardiomyocytes and are
      major determinants of electrical conduction in the heart. Altered distribution
      and function of connexin 43 (Cx43), the major gap junctional protein in the
      ventricles, can slow conduction, and thus contribute to arrhythmogenesis in
      experimental models such as ischemic rat heart and pacing-induced atrial
      fibrillation. The mechanisms underlying reduced gap junctional density and
      conductance during ischemia may involve decreased Cx43 synthesis, increased
      degradation and/or Cx43 migration into areas which do not contribute to
      intercellular communication. To test more rigorously the hypothesis that hypoxia
      resulting from ischemia causes Cx43 internalization, we infected neonatal rat
      ventricular myocytes (NRVM) with a Cx43-GFP chimera, which enabled us to
      investigate by means of confocal microscopy the effect of hypoxia (1% O2 for 5 h)
      on Cx43 distribution in live cardiomyocytes. Importantly, this protocol permitted
      each culture to serve as its own control. To this end we used life confocal
      microscopy analysis to determine in the same pair of myocytes the effects of
      hypoxia on Cx43-GFP distribution at the gap junctional (GJ) and non-GJ areas. In
      support of this hypothesis, we found that compared to normoxia, 5 h of hypoxia
      reduced the Cx43-GFP signal at the GJ areas (defined as the border area) and
      caused a corresponding increase in the Cx43-GFP signal at the non-border areas,
      thus providing an additional explanation for the intercellular uncoupling during
      ischemic conditions.

PMID- 20817947
TI  - A possible role of NF-kappaB and HSP72 in skeletal muscle hypertrophy induced by
      heat stress in rats.
AB  - Effects of heat stress on phosphorylated nuclear factor-kappaB (phospho-NF
      kappaB) and tumor necrosis factor alpha (TNFalpha) contents in skeletal muscles
      were studied. Male Wistar rats (7-week-old) were randomly assigned to control and
      heat-stressed groups. Rats in heat-stressed group were exposed to heat stress (42
      degrees C for 60 min) in an incubator without anesthesia. Soleus muscles were
      dissected and weighted 1, 3, and 7 days after the heat exposure. Significant
      increases in the wet weight and protein content of soleus were observed 7 days
      following the exposure (p < 0.05). Heat stress also induced the up-regulation of
      heat shock protein 72 (HSP72), IkappaBalpha (inhibitor of NF-kappaB) and the
      increase in the relative population of Pax7-positive satellite cells to total
      muscle nuclei before the increase in muscle mass. The content levels of phospho
      NF-kappaB and TNFalpha were significantly decreased 1 and 3 days after heat
      stress, respectively (p < 0.05). A negative correlation between HSP72 and phospho
      NF-kappaB contents was observed 1 day after the heat exposure. These observations
      suggest that the decrease in NF-kappaB signaling may play a part of a role in
      heat stress-associated muscle hypertrophy.

PMID- 20817948
TI  - Three methods for estimation of changes in frequency characteristics of
      potentials elicited by long-lasting (fatiguing) activity of isolated muscle
      fibres.
AB  - The present study was assigned to compare the applicability and sensitivity of
      three different methods (discrete wavelet transforms (DWT), median frequency
      (MDF) - calculated on the basis of fast Fourier transform, and spectral indices)
      for analysis of frequency content changes in potentials produced by repetitive
      stimulation from isolated slow (SMFs)- and fast (FMFs)-fatigable muscle fibers
      during uninterrupted activity. In order to affect fatigue, prior to starting the
      fatiguing stimulation (5 Hz), some of the fibres were exposed to microwave
      electromagnetic field and others were sham exposed. All the methods studied
      demonstrated that during a long-lasting fibre activity, the shift of the
      potential frequency content to lower frequencies was a consequence of lowering in
      higher frequency components and increasing in low frequency ones. The changes
      were faster in FMFs than SMFs and stronger in sham exposed fibres vs. microwave
      exposed. The MDF alterations in both fibre types and protocols were quite similar
      to other methods characterizing either individual changes in low and high
      frequency scales of the signal (discrete wavelet transform - DWT) or changes in
      their spectral ratio (spectral indices). The spectral indices showed sensitivity
      to fatigue effect at the final stages that made their changes considerably non
      linear. DWT allowed processing the temporal occurrence of frequency content
      changes that corresponded to the alterations in the separate potential phases as
      well as earlier detection and precise evaluation of fatigue onset and
      progressing. All methods are applicable but DWT is a preferable for study of
      muscle fibre fatigue in clinical and experimental neurophysiology.

PMID- 20817949
TI  - Rate of oxidative modification of cytochrome c by hydrogen peroxide is modulated
      by Hofmeister anions.
AB  - Cytochrome c (cyt c) and other heme proteins are oxidatively modified in the
      presence of hydrogen peroxide in a concentration- and time-dependent manner. Cyt
      c modification has been monitored by several spectral probes by absorption
      spectroscopy (at wavelengths 410 nm, 530 nm), and circular dichroism (222, 268,
      288 and 417 nm). Kinetics monitored with these spectral probes indicates that the
      oxidative modification of cyt c: i) proceeds in the order: heme --> aromatic
      amino acids --> secondary structure, and ii) the rate of the oxidative
      modification is proportional to the protein flexibility. The flexibility of cyt c
      was modulated by anions of Hofmeister series (sulfate, chloride, perchlorate)
      (Varhac et al. 2009). A minimalist scheme of the interaction of cyt c with
      hydrogen peroxide can be described by two steps: 1) interaction of hydrogen
      peroxide with heme iron forming the postulated ferryl intermediate, 2a) oxidation
      of another molecule of hydrogen peroxide and 2b) parallel oxidation of close
      amino acid residue(s) and/or heme. The catalase activity of cyt c is independent
      from the presence of Hofmeister anions, which indicates that both steps (1 and
      2a) in the catalase reaction are independent from the flexibility of the heme
      region of the protein matrix. On the other hand, the flexibility of the
      polypeptide chain of the protein modulates the rate of parallel oxidative
      modification of the heme and amino acid residues.

PMID- 20817950
TI  - Influence of sub-chronic diabetes mellitus on functional properties of renal
      Na(+),K(+)-ATPase in both genders of rats.
AB  - For characterization of Na(+),K(+)-ATPase, a key enzyme involved in maintenance
      of intracellular sodium homeostasis, expression of alpha1 subunit and the ATP-
      and Na(+)-binding properties were investigated by Western blot analysis and by
      enzyme kinetics, respectively. Previous studies documented time-dependent
      alteration of properties of renal Na(+),K(+)-ATPase from its mobilization after 8
      days to serious deteriorations after 16 weeks of diabetes in rats. Characterizing
      the critical period during development of the disease, when mobilization of
      Na(+),K(+)-ATPase observed in the acute phase turns to its damage, we examined
      the enzyme properties after 8 weeks lasting diabetes which was induced by a
      single intraperitoneal administration of streptozotocin in a dose of 65 mg.kg(
      1). The unchanged expression of Na(+),K(+)-ATPase alpha1-subunit in both genders
      indicates that 8 weeks represent the time when the mobilization of enzyme
      synthesis observed previously in acute diabetes is lost. In this time the renal
      Na(+),K(+)-ATPase undergoes structural changes in the vicinity of Na(+)-binding
      site resulting in worsened affinity to sodium in both genders as indicated by 13%
      and 18% increase of K(Na) value in female and male rats, respectively. However,
      gender specific was the diabetes-induced decrease in affinity to ATP by 18% which
      occurred in female rats only.

PMID- 20817951
TI  - Exposure to fractionated dose of 60 Gy affects molecular response of HL-60 cells
      to irradiation.
AB  - In this work we evaluated changes in molecular response of human promyelocyte
      leukemia cells HL-60 and HL-60-IR cells (HL-60 irradiated by 10 cycles of
      radiation with total dose of 60 Gy, given over a period of 3 months) to
      irradiation by the dose of 2 and 8 Gy. Analysis of CD11b and apoptosis by flow
      cytometry revealed that on 3rd day after irradiation by 8 Gy the HL-60-IR are
      more resistant to radiation-induced apoptosis and more differentiated (increase
      in CD11b in non-apoptotic cells) than regular HL-60. We found that both types of
      cells have high basal level of phosphorylated extracellular signal-regulated
      kinases Erk1/2 . Irradiation induces decrease in Erk1/2 phosphorylation after 4
      and 8 h in both cell types. However, in HL-60-IR cells Erk1/2 phosphorylation is
      restored faster than in HL-60. Also it was found that in contrary to HL-60 cells,
      the HL-60-IR cells react to 2 Gy irradiation by p53 independent increase in
      p21(WAF1/Cip1), and not by activation of checkpoint kinase Chk-2. Therefore we
      concluded that relatively high dose of radiation (6 Gy) does not lead after 10
      repetitive irradiations to eradication of HL-60 cells, but instead increases
      their radioresistance, increases the ability to differentiate, alters MAPK
      response, increases amount of p21(WAF1/Cip1), and decreases induction of
      apoptosis by ionizing radiation. p21(WAF1/Cip1) might prevent apoptosis induction
      and trigger permanent cell-cycle arrest, which can also contribute to regression
      of this leukaemia after therapy.

PMID- 20817952
TI  - An investigation of the heart rate, heart rate variability, cardiac ions,
      troponin-I and CK-MB in men exposed to 1.5 T constant magnetic fields.
AB  - The aim of this study was to investigate heart rate (HR), heart rate variability
      (HRV) and other cardiac parameters in individuals who were exposed to a high
      static magnetic field. 30 healthy male volunteers aged between 20-30 years were
      included. The searching was divided into three phases: pre-magnetic field, during
      the magnetic field and post-magnetic field. Every phase lasted 30 minutes. Pulse,
      systolic and diastolic blood pressure, respiration rate and elektrocardiography
      (ECG), recorded for 30 minutes, in all of the individuals were measured during
      three phases. The men were exposed to a 1.5 T static magnetic field. The levels
      of Na(+), K(+), Ca(2+), Cl(-), CK-MB, troponin-I and HR and HRV parameters were
      investigated. There was an increase in the respiration rate, and no change in the
      systolic and diastolic blood pressure and pulse in the individuals exposed to the
      magnetic field. There was also an enhancement in the values of ions, CK-MB and
      troponin-I after exposure to the magnetic field. Heart rate parameters (minimum
      HR-I, maximum HR-I, average HR-I) were decreased and rMSSD, pNN50, power, VLF,
      HF, LF values increased during the magnetic field.

PMID- 20817954
TI  - A mechanistic interpretation of root transport of water.
AB  - The present paper offers a mechanistic interpretation of filtration coefficients
      L(pr) in isolated maize roots, measured with the use of the root pressure probe
      by Steudle and others (Steudle 1990, 1992; Steudle and Brickmann 1989; Steudle
      and Frensch 1989; Steudle and Jeschke 1983; Steudle et al. 1993) on the basis of
      the Kedem-Katchalsky equations. Detailed investigations have been based on the
      mechanistic equations of solute and solvent membrane transport across porous
      membranes (Kargol 2001; Kargol and Kargol 2003a,b). It must be stressed that
      transport equations of both these (thermodynamic and mechanistic) formalisms are
      mutually compatible, which has been demonstrated for instance in the works Kargol
      and Kargol (2003) and Suchanek (2005, 2006).

PMID- 20817953
TI  - Effects of acute exposure to static magnetic field on ionic composition of rat
      spinal cord.
AB  - The purpose of this study is to evaluate the effect of static magnetic fields
      (SMF) on ionic composition of rat spinal cord. Male Wistar rats were daily
      exposed to SMF of 128 mT, for 1 h/day during five consecutive days. Spinal cord
      samples were extracted, weighed and mixed in bidstilled water in order to be
      analyzed by inductively coupled plasma (ICP). Plasma ionic composition was also
      made. Acute exposure to SMF increased significantly the calcium (+68%, p < 0.05)
      and iron (+35%, p < 0.05) contents of rat spinal cord, whereas magnesium and
      copper levels remained unchanged. In plasma, SMF treatment failed to alter
      calcium concentration but decreased iron level (-17%, p < 0.05). These data
      indicate that SMF acute exposure can induce alterations of ionic composition in
      the rat spinal cord and the plasma electrolytes balance.

PMID- 20817955
TI  - Accelerated removal of deamidated proteins and endogenous electric fields:
      possible implications.
AB  - Changes in protein structure through the spontaneous deamidation of asparaginyl
      (Asn) and glutaminyl (Gln) residues have been observed in many proteins. Amide
      residues were supposed to serve as clocks for development and aging. Deamidated
      proteins are rapidly degraded by as yet unclear molecular mechanisms. Deamidation
      leads to elevation of the ratio of charged versus polar residues (CH-PO) of a
      protein and to a decrease in its pI value. We had reported that those enzymes,
      characterized by a high CH-PO, are prone to inactivation and loss of ordered
      structure by exposure to direct current from low voltage in solution. Nano-local
      endogenous electric fields arise within cells. Endogenous currents may cause the
      unfolding of the products of deamidation at Asn. In turn, these unfolded proteins
      would be removed, likely by proteolysis.

PMID- 20817956
TI  - Drug-induced changes in action potential duration are proportional to action
      potential duration in rat ventricular myocardium.
AB  - Several cardioactive agents exhibit direct or reverse rate-dependent effects on
      action potential duration (APD) depending on the experimental conditions.
      Recently, a new theory has been proposed, suggesting that the reverse rate
      dependent mode of drug-action may be a common property of canine, rabbit, guinea
      pig and human cardiac tissues, and this phenomenon is based on the dependence of
      drug-action on baseline APD. The aim of the present work was to examine the
      limitations of this hypothesis by studying the APD lengthening effect of K(+)
      channel blockers and the APD shortening effect of Ca(2+) channel blockers during
      the electrical restitution process of rat ventricular action potentials. Rat
      ventricular muscle was chosen because it has a set of ion currents markedly
      different from those of other species, its APD is shorter by one order of
      magnitude than that of the "plateau-forming" larger mammals, and most
      importantly, its APD increases at higher heart rates - opposite to many other
      species. The restitution of APD was studied as a function of the diastolic
      interval, a parameter indicating the proximity of action potentials. It was found
      that drug-induced APD changes in rat myocardium are proportional with the pre
      drug value of APD but not with the diastolic interval, indicating that not the
      proximity of consecutive action potentials, but the baseline APD itself may
      determine the magnitude of drug-induced APD changes.

PMID- 20817958
TI  - Conducting polymer-based nanostructurized materials: electrochemical aspects.
AB  - New modern technologies require new materials. During the past decade, the
      movement towards nanodimensions in many areas of technology aroused a huge
      interest in nanostructurized materials. The present article reviews recent works
      dealing with electrochemistry-related aspects of nanostructurized conducting
      polymers. Electrochemical synthesis and some properties of nanostructurized
      conducting polymers, and nanocomposites derived from conducting polymers and
      metals, carbon, and inorganic and organic materials are considered. Some
      potential areas for electrochemistry-related applications of nanocomposites are
      highlighted, including batteries, supercapacitors, energy conversion systems,
      corrosion protection, and sensors.

PMID- 20817957
TI  - Muscle-specific inositide phosphatase (MIP/MTMR14) is reduced with age and its
      loss accelerates skeletal muscle aging process by altering calcium homeostasis.
AB  - We have recently reported that a novel muscle-specific inositide phosphatase
      (MIP/MTMR14) plays a critical role in [Ca2+]i homeostasis through
      dephosphorylation of sn-1-stearoyl-2-arachidonoyl phosphatidylinositol (3,5)
      bisphosphate (PI(3,5)P2). Loss of function mutations in MIP have been identified
      in human centronuclear myopathy. We developed a MIP knockout (MIPKO) animal model
      and found that MIPKO mice were more susceptible to exercise-induced muscle
      damage, a trademark of muscle functional changes in older subjects. We used wild
      type (Wt) mice and MIPKO mice to elucidate the roles of MIP in muscle function
      during aging. We found MIP mRNA expression, MIP protein levels, and MIP
      phosphatase activity significantly decreased in old Wt mice. The mature MIPKO
      mice displayed phenotypes that closely resembled those seen in old Wt mice: i)
      decreased walking speed, ii) decreased treadmill activity, iii) decreased
      contractile force, and iv) decreased power generation, classical features of
      sarcopenia in rodents and humans. Defective Ca2+ homeostasis is also present in
      mature MIPKO and old Wt mice, suggesting a putative role of MIP in the decline of
      muscle function during aging. Our studies offer a new avenue for the
      investigation of MIP roles in skeletal muscle function and as a potential
      therapeutic target to treat aging sarcopenia.

PMID- 20817959
TI  - Novel one-dimensional nanogap created with standard optical lithography and
      evaporation procedures.
AB  - This article details a simple four-step procedure to create a one-dimensional
      nanogap on a buried oxide substrate that relies on conventional photolithography
      performed on a stack of silicon/silicon oxide/silicon, metal evaporation, and
      hydrofluoric acid oxide removal. Once the nanogap was fabricated it was bridged
      with an assembly of 1,8-octanedithiol and 5 nm Au nanoparticles capped with a
      sacrificial dodecylamine coating. Before assembly, characterization of the
      nanogaps was performed through electrical measurements and SEM imaging. Post
      assembly, the resistance of the nanogaps was evaluated. The current increased
      from 70 fA to 200 microA at +1 V bias, clearly indicating a modification due to
      nanoparticle molecule assembly. Control experiments without nanoparticles or
      octanedithiol did not show an increase in current.

PMID- 20817960
TI  - Control of power law scaling in the growth of silicon nanocolumn pseudo-regular
      arrays deposited by glancing angle deposition.
AB  - Nanocolumn pseudo-regular arrays of silicon with controlled aspect ratio and
      porosity are fabricated by electron-beam evaporation using the glancing angle
      deposition (GLAD) method with vapour impinging at oblique incidence onto rapidly
      rotating substrates. The width W at positions y along the height of one
      individual column scales with y following a power law dependence W approximately
      y(p). We demonstrate that the scaling exponent value, p, can be modified from 0.6
      to 0.3 by varying the vapour incidence angle from 75 degrees to a glancing 89
      degrees from the substrate normal. This exponent is an important morphological
      factor for thin films, as it determines the morphological correlation length,
      nanocolumn profile, size, and spacing. The nanocolumn mean diameter can be varied
      between 12 and 40 nm, while the intercolumnar spacing can be adjusted between 37
      and 85 nm via changing the incidence angle. The growth mechanism and film
      morphology are explored in detail.

PMID- 20817961
TI  - Long-range interactions between transcription factors.
AB  - We discuss a method for analysing the number of GFP-LacI fusion transcription
      factors bound to a construct of 256 contiguous LacI binding sites using photon
      bleaching statics. We show by using a combination of imaging of the construct in
      nanochannels, photon statistics and addition of IGFP that the binding coefficient
      of the LacI decreases with increasing occupation of the construct, with a binding
      coefficient of 10(-6) M when only 15 of the 256 possible sites are occupied. We
      model this effect by assuming that the GFP-LacI dimer introduces elastic strain
      into the helix by generalized deformations, and that this strain propagates over
      distances at least as large as the persistence length.

PMID- 20817962
TI  - The use of heat transfer fluids in the synthesis of high-quality CdSe quantum
      dots, core/shell quantum dots, and quantum rods.
AB  - Fluorescent semiconductor nanoparticles, or quantum dots, have potential uses as
      an optical material, in which the optoelectronic properties can be tuned
      precisely by particle size. Advances in chemical synthesis have led to
      improvements in size and shape control, cost, and safety. A limiting step in
      large-scale production is identified to be the raw materials cost, in which a
      common synthesis solvent, octadecene, accounts for most of the materials cost for
      a batch of CdSe quantum dots. Thus, less expensive solvents are needed. In this
      paper, we identify heat transfer fluids, a class of organic liquids commonly used
      in chemical process industries to transport heat between unit operations, as
      alternative solvents for quantum dot synthesis. We specifically show that two
      heat transfer fluids can be used successfully in the synthesis of CdSe quantum
      dots with uniform particle sizes. We show that the synthesis chemistry for
      CdSe/CdS core/shell quantum dots and CdSe quantum rods can also be performed in
      heat transfer fluids. With the aid of a population balance model, we interpret
      the effect of different HT fluids on QD growth kinetics in terms of solvent
      effects, i.e., solvent viscosity, CdSe bulk solubility in the solvent, and
      surface free energy.

PMID- 20817963
TI  - Magnetic properties of epsilon-Fe(3)N-GaN core-shell nanowires.
AB  - epsilon-Fe(3)N-GaN core-shell nanowires are synthesized by the wet chemical route
      and by nitridation of the Fe-Ga-oxide nanowires in flowing NH(3) (g). The
      encapsulation by the GaN shell protects the epsilon-Fe(3)N core and spin-glass
      like cooperative ordering is observed at low temperatures. Magnetic disorder
      occurs at the epsilon-Fe(3)N-GaN interface, giving rise to the spin-glass-like
      state below 50 K because of the presence of anti-ferromagnetic (AF) mixed
      oxynitrides and ferromagnetic (FM) epsilon-Fe(3)N nitride and the random
      distribution of epsilon-Fe(3)N in the interface region. The spin-glass-like
      ordering is probed by relaxation and ac susceptibility experiments.

PMID- 20817964
TI  - Structural and mechanical characterization of nanoclay-reinforced agarose
      nanocomposites.
AB  - Nanoclay-reinforced agarose nanocomposite films with varying weight concentration
      ranging from 0 to 80% of nanoclay were prepared, and structurally and
      mechanically characterized. Structural characterization was carried out by
      transmission electron microscopy (TEM), scanning electron microscopy (SEM) and
      atomic force microscopy (AFM). It was found that pre-exfoliated clay platelets
      were re-aggregated into particles (stacked platelets) during the composite
      preparation process. Each particle consists of approximately 11 clay platelets
      stacked together. The nanoclay particles were homogeneously dispersed within an
      agarose matrix. The clay particles were oriented with a slight preference of the
      stacked platelets being parallel to the composite film's surface within the low
      loading composite films. Mechanical properties of the nanocomposite films were
      measured by tensile, three-point bending and nanoindentation tests. Mechanical
      testing results show that nanoclays provide a significant enhancement to the
      tensile modulus and strength. For the 60% clay nanocomposite, its elastic modulus
      increases up to 21.4 GPa, which is five times higher than that of the agarose
      matrix. Based upon the structural characterization, a theoretical model has been
      developed to simulate the mechanical behaviour of the nanoclay-reinforced polymer
      composites.

PMID- 20817965
TI  - Synthesis of copper nanowires under a direct current electric field.
AB  - Nanowires composed of pure copper were synthesized using (KI)(1.5)(CuI)(8.5) thin
      film under a direct current electric field (DCEF). The (KI)(1.5)(CuI)(8.5) film
      was used as the medium for transmitting cuprous ions. Investigation shows the
      copper nanowires with diameters in the range of 20-150 nm were single crystals
      with a face-centred cubic (fcc) structure. The electric field strength (EFS) was
      also found to play an important role in determining the diameter of the
      nanowires.

PMID- 20817966
TI  - Doped ZnS:Mn nanoparticles obtained by sonochemical synthesis.
AB  - A study of sonochemically synthesized ZnS:Mn nanoparticles is presented. The
      particles prepared at low rf power (about 20 W) and room temperature coalesce to
      form morphologically amorphous large species (30-100 nm in diameter). As the
      power is increased in the range from 20 to 70 W, and the solution temperature is
      raised to 60 to 80 degrees C, finer particles are produced with the size ranging
      from 2 to 20 nm and improved crystallinity. The results indicate the dispersion
      of the Mn(2+) ions at near-surface sites in the particles. It is shown that the
      sonochemically fabricated particles approach the quality of the ones obtained by
      a standard chemical route and show a reasonable luminescence performance.

PMID- 20817967
TI  - Fabrication, characterization and field emission properties of large-scale
      uniform ZnO nanotube arrays.
AB  - Large-scale well-aligned ZnO nanotubes with outer diameters of 100-300 nm and
      lengths of tens of micrometres have been prepared by a template-based chemical
      vapour deposition method. The photoluminescence spectrum of the ZnO nanotube
      arrays consists of a strong violet band at 414 nm, a blue band at 462 nm and a
      weak shoulder peak at around 480 nm. The field emission of the ZnO nanotube
      arrays shows a turn-on field of about 7.3 V microm(-1) at a current density of
      0.1 microA cm(-2) and emission current density up to 1.3 mA cm(-2) at a bias
      field of 11.8 V microm(-1).

PMID- 20817968
TI  - Size control of ZnO nanorod arrays grown by metalorganic chemical vapour
      deposition.
AB  - The size control of vertically aligned ZnO nanorod arrays (NRAs) grown by
      catalyst-free metalorganic chemical vapour deposition is accomplished by changing
      the O/Zn precursor ratio. At a higher O/Zn precursor ratio, fat ZnO NRAs with
      excellent alignment are produced. In contrast, slim ZnO NRAs that are
      considerably less well aligned grow at a lower O/Zn precursor ratio. Irrespective
      of their different sizes and alignments, the individual ZnO nanorods are of a
      defect-free single-crystalline nature and of high optical quality, indicating
      that changing the precursor ratio is a promising way of fabricating size
      controlled ZnO NRAs.

PMID- 20817969
TI  - In situ formation of Ag flowerlike and dendritic nanostructures in aqueous
      solution and hydrolysis of an amphiphilic block copolymer.
AB  - Silver flowerlike and dendritic nanostructures were synthesized in an aqueous
      solution of a hydrolysable amphiphilic block copolymer polyvinylacetone (PVKA)
      via in situ reduction of Ag(+) and hydrolysis of PVKA at room temperature.
      Compared with a previous result, the complete hydrolysis time of PVKA is greatly
      shortened in this process.

PMID- 20817970
TI  - Microfluidic ultramicroscale deposition and patterning of quantum dots.
AB  - The ability to directly deposit materials in ultraminiaturized domains with
      nanoscale accuracy could play a central role in the realization of some forms of
      nanotechnology. In this report we demonstrate the direct deposition of quantum
      dots in patterns with ultramicroscale (1-15 microm) and nanoscale (<1 microm)
      features. Unlike bottom up approaches that require preconfigured patterning
      steps, this top down 'direct write' method should be amenable to the construction
      of a large variety of patterns and features essentially 'on the fly'. To
      accomplish the direct writing/deposition of quantum dots we used a system that
      integrates high resolution motion control with microfabricated fluid delivery
      cartridges. This process is termed FEMTO (fluidics enhanced molecular transfer
      operation). The methodology demonstrated here may be extended to surface
      patterning and deposition of a broad spectrum of other nanoscale materials and
      thereby create opportunities in a variety of fields ranging from microelectronics
      to bio/nanotechnology.

PMID- 20817971
TI  - Fabrication of a lotus-like micro-nanoscale binary structured surface and
      wettability modulation from superhydrophilic to superhydrophobic.
AB  - We report a simple method for fabricating a lotus-like micro-nanoscale binary
      structured surface of copper phosphate dihydrate. The copper phosphate dihydrate
      nanosheets were generated by galvanic cell corrosion of a copper foil with
      aqueous phosphorus acid solution drops and dried in an oxygen gas atmosphere, and
      they self-organized into a film with a lotus-like micro-nanoscale binary
      structured surface. The wettability of this surface can be changed from
      superhydrophilic to highly hydrophobic or superhydrophobic by heating or
      modifying it with an n-dodecanethiol monolayer.

PMID- 20817972
TI  - Electric-field assisted immobilization and hybridization of DNA oligomers on thin
      film microchips.
AB  - Single, square voltage pulses in the microsecond timescale result in selective 5'
      end covalent bonding (immobilization) of thiolated single-stranded (ss) DNA
      probes to a modified silicon dioxide flat surface and in specific hybridization
      of ssDNA targets to the immobilized probe. Immobilization and hybridization rates
      using microsecond voltage pulses at or below 1 V are at least 10(8) times faster
      than in the passive control reactions performed without electric field (E), and
      can be achieved with at least three differently functionalized thin-film surfaces
      on plastic or glass substrates. The systematic study of the effect of DNA probe
      and target concentrations, of DNA probe and target length, and the application of
      asymmetric pulses on E-assisted DNA immobilization and hybridization showed that:
      (1) the rapidly rising edge of the pulse is most critical to the E-assisted
      processes, but the duration of the pulse is also important; (2) E-assisted
      immobilization and hybridization can be performed with micrometre-sized pixels,
      proving the potential for use on microelectronic length scales, and the applied
      voltage can be scaled down together with the electrode spacing to as low as 25
      mV; and (3) longer DNA chains reduce the yield in the E-assisted immobilization
      and hybridization because the density of physisorbed single-stranded DNA is
      reduced. The results show that the E-induced reactions can be used as a general
      method in DNA microarrays to produce high-density DNA chips (E-immobilization)
      and speed the microarray-based analysis (E-hybridization).

PMID- 20817973
TI  - Large-area synthesis of high-quality beta-MnO(2) nanowires and the mechanism of
      formation through a facile mineralization process.
AB  - High-quality large-area beta-MnO(2) nanowires can be easily synthesized using
      KNO(3) as the mineralizing agent in a process of mineralization from Mn(NO(3))(2)
      aqueous solution. The morphological evolution of the beta-MnO(2) nanowires and
      the influences of mineralizing agents and their concentrations on the morphology
      of the final products were investigated in detail. KNO(3) was the best
      mineralizing agent among KNO(3), NaNO(3), KCl, and NaCl. More interestingly, when
      the concentration of the mineralizing agent KNO(3) was not saturated, only
      irregular short faceted nanorods, instead of nanowires, can be observed. Finally,
      the formation mechanism is discussed.

PMID- 20817974
TI  - Artificial nanograting woven by self-assembled nanowires.
AB  - We report on a new simple route to realize a high resolution nanograting. By
      adopting an InAlGaAs matrix and strain-compensated technique, we have proved that
      a uniform self-assembled InAs nanowire array can be fabricated by molecular beam
      epitaxy (MBE). A nanograting woven by self-assembled semiconductor nanowires
      shows a conspicuous diffraction feature. The good agreement between the
      theoretical and experimental values of diffraction peak positions indicates that
      a uniform nanowire array is a promising nanograting. This simple one-step MBE
      growth method will open exciting opportunities for the field of clever optics
      design.

PMID- 20817975
TI  - Atomic force microscope anodization lithography using pulsed bias voltage
      synchronized with resonance frequency of cantilever.
AB  - An applied bias voltage between the atomic force microscope tip and the substrate
      is one of the important factors related to the growth of oxide patterns. A pulse
      modulator was used to apply a pulsed bias voltage that synchronizes with the
      resonance frequency of the cantilever between the tip and the substrate in
      tapping mode. The height of the protruded oxide structure was increased for short
      duration times of the pulsed bias due to the reduction of built-up space charge
      in oxide. The aspect ratio of patterns using pulsed bias voltage was about two
      times higher than that using continuous bias voltage. This study revealed that
      the pulsed bias has an advantage for obtaining a higher aspect ratio pattern than
      the continuous bias by reducing the effect of space charge in oxide.

PMID- 20817976
TI  - Resonance analysis of multi-layered graphene sheets used as nanoscale resonators.
AB  - A stacked plate model for the vibration of multi-layered graphene sheets (MLGSs),
      in which the van der Waals (vdW) interaction between layers is described by an
      explicit formula, is presented. Explicit formulae are derived for predicting the
      natural frequencies of double- and triple-layered graphene sheets, and they
      clearly indicate the effect of vdW interaction on the natural frequencies. The
      natural frequencies are calculated for various numbers of layered graphene
      sheets, and the results show that the vdW interaction has no influence on the
      lowest natural frequency (classical frequency) of an MLGS but plays a significant
      role in all higher natural frequencies (resonant frequencies) for a given
      combination of m and n. The vibration modes that are associated with the
      classical frequencies for each sheet of an MLGS are identical. In contrast, the
      vibration modes that are associated with the resonant frequencies are non
      identical and give various vibration patterns, which indicates that MLGSs are
      highly suited to use as high frequency resonators.

PMID- 20817977
TI  - Formation of a rosette pattern in copper nitride thin films via nanocrystals
      gliding.
AB  - By sputtering synthesis of cubic Cu(3)N, which decomposes at moderate
      temperatures, film growth proceeds with simultaneous nitrogen reemission from
      inside, leading to the formation of some unusual structures or morphology. We
      report a relief morphology comprising densely packed rosette-like features. The
      rosettes, typically 20 microm in size, show a radial furcation followed by
      successive bifurcation at approximately 74 degrees , resulting in a fivefold
      symmetric structure sometimes. The area expansion of the features can be as large
      as ten per cent with regard to the underlying bottom. Scanning electron
      micrographs reveal that it is the gliding of Cu(3)N nanocrystals along the Cu
      rich {111}-planes that is responsible for the unusually large area expansion. The
      gliding and packing along the {111}-planes also explain the bifurcation angle of
      the ramified rosettes. Such a relief morphology can serve as a template for large
      area fabrication of concave structures by inverse duplication, adding to the
      already abundant innovative applications of this material.

PMID- 20817978
TI  - Fabrication and anomalous transport properties of an Sb/Bi segment nanowire
      nanojunction array.
AB  - An Sb (40 nm diameter)-Bi (30 nm diameter) segment nanowire nanojunction array
      was fabricated by pulsed electrodeposition. Electric transport properties of the
      junction array were studied down to 4.2 K and in magnetic fields up to 5 T.
      Temperature versus resistance measurements exhibited a resistive switching
      behaviour at zero magnetic field, but this feature disappeared with increasing
      magnetic field. These features might find application in sub-100 nm metal
      semiconductor field effect transistors.

PMID- 20817979
TI  - Fabrication of nanopeas with ZnSe-filled SiO(2) nanotube/nanowire configuration.
AB  - Composite nanopeas with ZnSe nanodots/rods embedded in an SiO(2) nanowire/tube
      configuration have been fabricated via a simple thermochemistry method. The
      nanopeas are uniform with an average outer diameter of approximately 80 nm. The
      SiO(2) nanowires/tubes are amorphous, whereas the encapsulated ZnSe nanodots/rods
      are single crystalline. Two key experimental factors are identified for the
      composite nanopea formation, which enables such methodology to be generally
      applied to a variety of other material systems.

PMID- 20817980
TI  - The selectively manipulated growth of crystalline ZnO nanostructures.
AB  - Aligned ZnO nanorods on film, tetrapod nanowires and nanotubes have been
      selectively fabricated by a simple one-step route and characterized by x-ray
      diffractometry (XRD), transmission electron microscopy (TEM), high-resolution TEM
      (HRTEM) and photoluminescence (PL). PL spectra exhibit different intensity of the
      green emission relative to the UV emission for different nanostructures. The
      effects of the process parameters on different nanostructures have been
      discussed. The wettability of well aligned nanorods on film was investigated,
      which reveals a super-hydrophobicity.

PMID- 20817981
TI  - Template-free electrodeposition of multicomponent metal nanoparticles for region
      specific growth of interposed carbon nanotube micropatterns.
AB  - We have demonstrated that multicomponent carbon nanotube micropatterns, in which
      different nanotubes are interposed in an intimate fashion, can be prepared by
      pyrolytic growth of carbon nanotubes on interposed micropatterns of different
      metal nanoparticles generated by template-free pulsed electrodeposition of metal
      containing salts onto a photolithographically prepatterned conductive surface at
      different peak potentials. The resultant multicomponent interposed carbon
      nanotube micropatterns should have important implications for the construction of
      multicomponent and multifunctional nanomaterials and nanodevices based on carbon
      nanotubes for a wide range of potential applications.

PMID- 20817982
TI  - Van der Waals-corrected density functional theory: benchmarking for hydrogen
      nanotube and nanotube-nanotube interactions.
AB  - Density functional theory (DFT) is a powerful approach to electronic structure
      calculations in extended systems, but suffers currently from inadequate
      incorporation of long-range dispersion, or Van der Waals (VdW) interactions. VdW
      corrected DFT is tested for interactions involving molecular hydrogen, graphite,
      single-walled carbon nanotubes (SWCNTs), and SWCNT bundles. The energy
      correction, based on an empirical London dispersion term with a damping function
      at short range, allows a reasonable physisorption energy and equilibrium distance
      to be obtained for H(2) on a model graphite surface. The VdW-corrected DFT
      calculation for an (8, 8) nanotube bundle reproduces accurately the experimental
      lattice constant. For H(2) inside or outside an (8, 8) SWCNT, we find the binding
      energies are respectively higher and lower than that on a graphite surface,
      correctly predicting the well known curvature effect. We conclude that the VdW
      correction is a very effective method for implementing DFT calculations, allowing
      a reliable description of both short-range chemical bonding and long-range
      dispersive interactions. The method will find powerful applications in areas of
      SWCNT research where empirical potential functions either have not been
      developed, or do not capture the necessary range of both dispersion and bonding
      interactions.

PMID- 20817983
TI  - Chemical synthesis and magnetic properties of well-coupled FePt/Fe composite
      nanotubes.
AB  - A simple two-step hydrogen reduction method was used to synthesize FePt/Fe
      composite nanotubes. As the first step, L1(0) FePt nanotubes were prepared by
      heating a porous alumina template loaded with an alcohol solution of a Fe
      chloride and Pt chloride mixture in flowing hydrogen at 670 degrees C. Then,
      FePt/Fe composite nanotubes were obtained by reducing the alcohol solution of the
      Fe chloride within the formed FePt nanotubes at a lower temperature, namely 470
      degrees C. Through changing the concentrations of initial alcohol solutions, the
      FePt:Fe atomic ratios of the composite nanotubes were easily adjusted and the
      magnetic properties were tuned accordingly. For (FePt)(100-x)/Fe(x) composite
      nanotubes with x ranging between 0 and 26 at.%, the hard and soft phases were
      well coupled and the coercivity was tunable over a large range (1.27-2.73 T).
      Furthermore, the marked interdiffusion between Fe and FePt, which usually exists
      in FePt-based composites fabricated by using conventional methods, was not
      observed in the formed composite nanotubes. This indicates the two-step hydrogen
      reduction method to be a promising route for synthesizing nanocomposites which
      are difficult to fabricate by using conventional methods due to the
      interdiffusion between different phases.

PMID- 20817984
TI  - Microemulsion-based solvothermal synthesis of aluminium orthophosphate
      nanocrystals.
AB  - Aluminium orthophosphate (AlPO(4)) nanocrystals were synthesized by a
      microemulsion-based solvothermal approach. The reaction temperature and
      concentration of reactants as well as the molar ratio of the two reactants have
      significant effects on the shape and size of the AlPO(4) nanocrystals obtained. A
      possible formation mechanism for the AlPO(4) nanocrystals with different shapes
      is discussed.

PMID- 20817985
TI  - Nanodiode based on a multiwall CN(x)/carbon nanotube intramolecular junction.
AB  - We prepared multiwall carbon nanotubes (MWCNTs) from the pyrolysis of ferrocene,
      and CN(x) nanotubes from a mixture of ferrocene and melamine. Under well chosen
      synthesis conditions, massive multiwall CN(x)/carbon nanotube intramolecular
      junctions were successfully fabricated. The individual nanotubes were used as
      conductance channels to obtain their transport characteristic information.
      Measurement results showed that the current-voltage (I-V) curve of the CN(x)/CNT
      junction is highly asymmetric, behaving like a diode. Moreover, the devices are
      very stable in ambient environment. We attribute this nonlinear property of the
      CN(x)/CNT junctions to their two different atomic and electronic sections.

PMID- 20817986
TI  - Fabrication of modified and functionalized polycaprolactone nanofibre scaffolds
      for vascular tissue engineering.
AB  - Electrospun polymer nanofibres were originally developed for their durability and
      resistance to all forms of degradation and biodegradation. Some polymer
      nanofibres are biocompatible and biodegradable and therefore suitable for
      replacement of structurally or physiologically deficient tissues and organs in
      humans. Here, biocompatible polycaprolactone (PCL) nanofibre scaffolds modified
      with collagen types I and III were used for vascular tissue engineering. Coronary
      artery smooth muscle cells (SMCs) were grown on PCL nanofibres, modified
      PCL/collagen biocomposite nanofibres and collagen nanofibres. The results show
      that the modified PCL/collagen biocomposite nanofibre scaffolds provide required
      mechanical properties for regulation of normal cell function in vascular tissue
      engineering.

PMID- 20817987
TI  - Resonant tunnelling through a C(60) molecular junction in a liquid environment.
AB  - We present electronic transport measurements through thiolated C(60) molecules in
      a liquid environment. The molecules were placed within a mechanically
      controllable break junction using a single anchoring group per molecule. On
      varying the electrode separation of the C(60)-modified junctions, we observed a
      peak in the conductance traces. The shape of the curves is strongly influenced by
      the environment of the junction as shown by measurements in two distinct
      solvents. In the framework of a simple resonant tunnelling model, we can extract
      the electronic tunnelling rates governing the transport properties of the
      junctions.

PMID- 20817988
TI  - In-flight size classification of carbon nanotubes by gas phase electrophoresis.
AB  - We demonstrate the use of gas phase electrophoresis to size classify CNTs grown
      in a continuous aerosol process. The separation process occurs at atmospheric
      pressure and involves electrostatic mobility separation which classifies fibres
      on the basis of equivalent projected surface area. This implies that one can, for
      diameter-controlled CNTs, obtain an on-the-fly determination of the CNT length
      distribution during CNT synthesis, or alternatively have a method for producing
      size separated CNTs. The method should be generic to any fibre based material.

PMID- 20817989
TI  - Investigation of single-walled carbon nanotube growth parameters using alcohol
      catalytic chemical vapour deposition.
AB  - A detailed parametric study of single-walled carbon nanotubes (SWNTs) synthesized
      in powder form and on substrates using the alcohol catalytic chemical vapour
      deposition (ACCVD) method is reported. As-grown SWNTs were analysed using
      transmission electron microscopy (TEM), field-emission scanning electron
      microscopy (FE-SEM), Raman spectroscopy and UV-vis-NIR spectroscopy to obtain
      structural and electronic information. We found that nucleation and growth of
      SWNTs occurs within seconds after introduction of the alcohol vapour and that
      high quality SWNTs with a narrow diameter distribution without amorphous carbon
      can be grown using Co acetate catalyst doped with Fe acetate above 750 degrees C.
      Defective multiwalled nanotubes were observed at lower temperatures, with the
      optimum temperature being 850 degrees C. These and other results reported in this
      paper allow the basis for optimizing the ACCVD process for the synthesis of large
      numbers of SWNTs.

PMID- 20817990
TI  - Well-ordered end-to-end linkage of gold nanorods.
AB  - In this study, it is found that as-prepared gold nanorods can be linked to each
      other in an end-to-end way by using cysteine as a molecular bridge. Both
      transmission electron microscopy and UV-visible optical spectroscopy demonstrated
      the uniaxial assembly of the gold nanorods. The controlled addition of cysteine
      into the gold nanorod solution resulted in their preferential binding to the two
      ends of the gold nanorods. As a result, end-to-end assembly was achieved through
      cooperative hydrogen bonding of bound cysteine molecules. The as-synthesized end
      to-end linked assembly of gold nanorods is well ordered and on a large scale. For
      comparison, three other neutral amino acids, glycine, alanine and valine, were
      also investigated but the orderliness of their assembly is not as good as that in
      the case of cysteine.

PMID- 20817991
TI  - An x-ray photoelectron spectra and atomic force microscopy characterization of
      silica substrates engineered with a covalently assembled siloxane monolayer.
AB  - Silica substrates were functionalized with a covalent 4-ClCH(2)C(6)H(4)SiCl(3)
      monolayer. Additional covalent bonding of appropriate functional molecules to the
      silylated substrates was further achieved. The surface chemical characterization
      was carried out by angle resolved x-ray photoelectron measurements. Moreover,
      surface morphological characterizations were performed by atomic force microscopy
      measurements. Present results provide step by step information on the covalently
      linked monolayer during the synthetic procedure.

PMID- 20817992
TI  - Nano-structured materials produced from simple metallic alloys by phase
      separation.
AB  - A method which is able to produce different types of nano-structured materials,
      namely nano-particles, nano-structured surfaces and nano-porous membranes, from
      two-phase metallic alloys is reviewed. The new process first establishes nano
      structures in the bulk alloy and then separates them by selective phase
      dissolution. Variation in processing makes it possible to produce different types
      of nano-structure even from the same alloy. The process can be applied to many
      different alloy systems. An overview is presented emphasizing the versatility of
      the process with examples of different nano-structure types that can be produced.
      Further, the new method is discussed in relation to similar processes
      (specifically, electrochemical processes) which have been used for nano-structure
      synthesis.

PMID- 20817993
TI  - A low temperature combination method for the production of ZnO nanowires.
AB  - The growth of large-area, patterned and oriented ZnO nanowires on silicon using a
      low temperature silicon-CMOS compatible process is demonstrated. Nanowire
      synthesis takes place using a thin nucleation layer of ZnO deposited by
      radiofrequency magnetron sputtering, followed by a hydrothermal growth step. No
      metal catalysts are used in the growth process. The ZnO nanowires have a wurtzite
      structure, grow along the c-axis direction and are distributed on the silicon
      substrate according to the pre-patterned nucleation layer. Room temperature PL
      measurements of the as-grown nanowires exhibit strong yellow-red emission under
      325 nm excitation that is replaced by ultraviolet emission after annealing. This
      method can be used to integrate patterned 1D nanostructures in optoelectronic and
      sensing applications on standard silicon CMOS wafers.

PMID- 20817994
TI  - Suspensions of nickel nanowires as magneto-optical switches.
AB  - Application of modest magnetic fields can be used to control the direction in
      which laser light incident on aqueous suspensions of magnetic Ni nanowires (
      approximately 200 nm in diameter and approximately 10 microm in length) is
      preferentially scattered. Similar effects were observed for suspensions of these
      nanowires prepared in ethanol, ethylene glycol, and glycerol. In glycerol, the
      nanowires settle sufficiently slowly that the effects can be quantified. In
      particular, fields of the order of 100 Oe cause the intensity of light scattered
      in the forward direction to vary by as much as a factor of thirty-five simply by
      changing the direction of the field.

PMID- 20817995
TI  - Electrical properties of Si-SiO(2)-Si nanogaps.
AB  - The chances of attaching organic molecules to silicon surfaces can be
      considerably enhanced if a robust nanogap structure with silicon electrodes can
      be used to connect the molecules. We describe the electrical properties of such
      an electrode structure, with a separation of the silicon surfaces in the 3-7 nm
      range. These silicon nanogaps are manufactured by partly removing the silicon
      dioxide insulator from a silicon-oxide-silicon material stack, by using a
      selective oxide etchant. After the activation of the gap (the etching), current
      instabilities appear, which are comparable to the properties of thin oxides after
      soft breakdown. Applying a constant voltage can reduce these current
      instabilities. We also address the issue of surface leakage currents for these
      nanogap structures.

PMID- 20817996
TI  - Buckling instabilities in GaN nanotubes under uniaxial compression.
AB  - We report experimental observations of shell buckling instabilities in free
      standing, vertically aligned GaN nanotubes subjected to uniaxial compression.
      Highly uniform arrays of the GaN nanotubes standing on a GaN template were
      fabricated and subjected to uniaxial compression using a nanoindenter. The
      buckling load was found to be of the order of 150 microN for the GaN nanotubes
      with an outer radius of 40 nm, an inner radius of 20 nm, and heights of 500 and
      300 nm. Good agreement was found between the experimental observations, the
      stress-strain relation equation study findings and the predictions from the
      cylindrical shell buckling theory.

PMID- 20817997
TI  - Anisotropic polarizability tensor of a dimer of nanospheres in the vicinity of a
      plane substrate.
AB  - We derive analytically the effective dipole polarizability tensor of a dimer of
      spheres located near a plane substrate. This is used to determine the extinction
      cross sections and other optical properties of the particles, and we use the
      results to study the experimentally observed red and blue shifts of the plasmon
      resonance of the dimer as a function of the distance between the particles or
      between the particles and the substrate. The results show that bringing the dimer
      towards the surface always leads to red shifted plasmon excitation. The plasmon
      resonance of the dimer may be red shifted or blue shifted as the particles are
      brought toward each other (at fixed distance from the surface) depending on the
      polarization. The size of the blue shift is smaller when the particles are close
      to the surface than when they are far away, but the red shifts are essentially
      unchanged.

PMID- 20817998
TI  - Carbon nanotube films for room temperature hydrogen sensing.
AB  - Thin, uniform, single-walled carbon nanotube films, made by a simple filtration
      process, subsequently coated with palladium, are shown to be promising detectors
      of hydrogen. The films detected hydrogen with relative responses of 20% at 100
      ppm and 40% at 500 ppm concentrations. Most of the initial film conductance was
      recovered within 30 s by exposing the samples to air. This quick and easy
      recoverability make the Pd-coated nanotubes suitable for practical applications
      in room temperature hydrogen sensing while consuming only approximately 0.25 mW
      power. The film fabrication process provides highly reproducible control over the
      film thickness; an important ingredient for commercial production. In the course
      of this research strong evidence was obtained indicating that sputter deposition
      of metal onto the nanotubes, even under very low power, short exposure time
      conditions, does damage to the nanotubes.

PMID- 20817999
TI  - Self-assembled growth and blue emission of a SiO(x)-capped (x = 0.5-0.8) silicon
      nanowire array.
AB  - A uniquely structured SiO(x)-capped (x = 0.5-0.8) Si nanowire array with strong
      blue emission, like a nanobeacon array, was fabricated using electroless metal
      (silver) deposition on a water plasma-treated Si wafer. Formation of the
      nanoscale light source array can be understood on the basis of a self-assembled
      localized microscopic electrochemical cell model and a diffusion-limited
      aggregation process. Photoluminescence spectral analysis reveals that the
      intensity of the broad blue-emitting luminescent band centred at around 435 nm
      strongly depends upon the irradiation of H(2)O(+), HO(+), and O(+) ions, which
      are present in the water plasma. We attribute the blue PL band to the optical
      transition of the self-trapped excitons at the surfaces of SiO(x) nanocaps.

PMID- 20818000
TI  - Measurement of the strength of adhesion of resist patterns using an atomic force
      microscope.
AB  - Atomic force microscopes (AFM) have been used to measure the strength of adhesion
      of photoresist patterns which generally collapse during rinsing with water in the
      development process. We suggest how to measure the collapsing force of the
      photoresist patterns using an AFM in which a lateral force microscope (LFM) is
      engaged to determine the tip load at the moment of pattern collapse. The AFM tip
      was precisely positioned in the space between the patterns in non-contact mode
      and then scanned in contact mode to the collapse patterns. Loads F for collapse
      on a scale of nanonewtons (nN) were calculated from the signal of the position
      sensitive photodiode. To investigate the variation of the collapsing load for
      different lengths of patterns, an AFM tip was also used to fabricate patterns
      with an appropriate length. Our method for measuring the strength of adhesion of
      photoresist patterns would enable an AFM to be applied to test this property for
      photoresists.

PMID- 20818001
TI  - Preparation and characterization of Ag(2)S nanoparticles embedded in polymer
      fibre matrices by electrospinning.
AB  - Polyvinylpyrrolidone (PVP)/Ag(2)S composite fibres were successfully prepared by
      a facile method called the electrospinning technique. Scanning electron
      microscopy analysis revealed the fibre morphology of the composite. Transmission
      electron microscopy showed spherical nanoparticles of the Ag(2)S component with
      an average particle size of about 15 nm and a good dispersion. X-ray diffraction
      results showed that a pure beta-Ag(2)S phase was obtained in the PVP fibres. X
      ray photoelectron spectra (XPS) proved that the Ag and S elements exist in
      PVP/Ag(2)S composite fibres and quantitative analysis of the XPS showed that the
      atomic ratio of silver and sulfur was about 2. Fourier transform infrared and
      ultraviolet-visible spectroscopy were used to characterize the structure of the
      PVP/Ag(2)S composite fibres.

PMID- 20818002
TI  - High-yield DNA-templated assembly of surfactant-wrapped carbon nanotubes.
AB  - We have developed a straightforward approach for constructing single-walled
      carbon nanotube (SWNT) assemblies by using aligned surface DNA as a positioning
      template. A cationic surfactant, dodecyltrimethylammonium bromide, is utilized to
      suspend SWNTs in aqueous media and localize them on DNA through electrostatic
      interactions. SWNT positioning is controlled by the surface DNA arrangement, and
      the extent of deposition is influenced by the SWNT concentration. With lower
      concentration SWNT suspensions, multiple surface treatments can increase the DNA
      coverage. Under optimized conditions, 83% of the length of surface DNAs was
      covered with SWNTs, and 76% of all surface-deposited SWNTs were on the DNA. In
      some regions, nearly continuous SWNT assemblies were formed. This approach should
      provide a useful tool for the fabrication of nanotube nanowires in nanoelectronic
      circuits.

PMID- 20818003
TI  - Synthesis and characterization of Nafion((R))-115 nanowire arrays.
AB  - Aligned Nafion((R))-115 nanowire arrays have been synthesized by an extrusion
      method with anodic aluminium oxide (AAO) membranes templates in this work. A
      surface modification was carried out to improve the hydrophobicity of the AAO
      pore surface. The as-synthesized nanowires are about 85 nm in diameter and
      several to over ten micrometres in length. Near-IR Raman and IR spectrum studies
      show that the polymer nanowires are composed of pure Nafion((R))-115 only.

PMID- 20818004
TI  - Use of dielectrophoresis in the fabrication of an atomic force microscope tip
      with a carbon nanotube: a numerical analysis.
AB  - To fabricate an atomic force microscope tip with an attached carbon nanotube
      (CNT), we simulated dielectrophoresis, produced by a nonuniform electric field.
      We calculated the dielectrophoretic force and torque of CNTs dispersed in a
      fluid. We then investigated the effect of various parameters such as the initial
      conditions of the CNT, the distance between the tip and the electrode, and the
      shape of the tip's apex. Using the results of the simulation, we examined the
      assembly conditions for achieving a high success rate. In particular, we found
      that the optimal distance between the tip and the electrode was 10 microm.

PMID- 20818005
TI  - Scaling constraints in nanoelectronic random-access memories.
AB  - Nanoelectronic molecular and magnetic tunnel junction (MTJ) MRAM crossbar memory
      systems have the potential to present significant area advantages (4 to 6F(2))
      compared to CMOS-based systems. The scalability of these conductivity-switched
      RAM arrays is examined by establishing criteria for correct functionality based
      on the readout margin. Using a combined circuit theoretical modelling and
      simulation approach, the impact of both the device and interconnect architecture
      on the scalability of a conductivity-state memory system is quantified. This
      establishes criteria showing the conditions and on/off ratios for the large-scale
      integration of molecular devices, guiding molecular device design. With 10%
      readout margin on the resistive load, a memory device needs to have an on/off
      ratio of at least 7 to be integrated into a 64 x 64 array, while an on/off ratio
      of 43 is necessary to scale the memory to 512 x 512.

PMID- 20818006
TI  - Feasibility study of the direct mechano-chemical synthesis of nanostructured
      magnesium tetrahydroaluminate (alanate) [Mg(AlH(4))(2)] complex hydride.
AB  - The present work reports a feasibility study of the direct mechano-chemical
      synthesis by controlled reactive mechanical alloying (CRMA) in a magneto-ball
      mill of the nanostructured magnesium tetrahydroaluminate (magnesium alanate)
      Mg(AlH(4))(2) complex hydride. Three stoichiometric Mg-2Al mixtures, (a)
      elemental Mg and Al powders, (b) elemental Al powder and commercial AZ91 alloy
      (Mg-Al-Zn alloy) and (c) powder of as-cast Mg-2Al alloy, have been used. No
      successful synthesis of Mg(AlH(4))(2) has been achieved. The only nanocrystalline
      hydride formed up to 270 h of CRMA is beta-MgH(2), and it does not react with Al
      and H(2) to form Mg(AlH(4))(2). It has been found that there is strong
      competition between formation of Al(Mg) solid solution and the beta-MgH(2)
      hydride occurring to a various extent up to approximately 10 h of CRMA in all
      three Mg-2Al mixtures. It is hypothesized that the presence of Al(Mg) solid
      solution inhibits the reaction of beta-MgH(2), Al and H(2) to form Mg(AlH(4))(2).
      Furthermore, despite the fact that after prolonged milling the Al(Mg) solution
      eventually decomposes into secondary Al(s) (derived from solid solution), the
      latter retains its physico-chemical characteristics of the former solid solution
      which still inhibits the reaction to form Mg(AlH(4))(2). Experimental evidence
      from DSC measurements shows increasing ranges of the melting enthalpy with
      increasing amounts of Al(Mg) solid solution and consequently the secondary Al(s)
      for all the three Mg-2Al mixtures. This strongly supports the hypothesis about
      the different nature of Al(Mg) and the secondary Al(s) as compared to the primary
      elemental Al powder.

PMID- 20818007
TI  - Fabrication of gold nanorod arrays by templating from porous alumina.
AB  - A simple procedure for fabrication of gold films with nanorod arrays is
      described. The method is based on thermal evaporation of gold onto a porous
      alumina (PA) membrane used as a template. The gold films were obtained after
      removing the template and characterized using scanning electron microscopy,
      atomic force microscopy and ultraviolet-visible spectrophotometry. The prepared
      gold films are composed of arrays of sharp (<20 nm at apex) rod-shaped gold
      nanostructures. These structures closely follow the organization and distribution
      of pores of the PA template. The length of the gold nanostructures is estimated
      to range from 300 nm to more than 1000 nm. It was found that their length is
      influenced by the size of the pores in the PA and the temperature of the PA
      during gold evaporation. Spectrophotometric characterization shows that the
      prepared gold films exhibit a surface plasmon resonance absorption peak located
      between 525 and 540 nm.

PMID- 20818008
TI  - Synthesis of single-crystalline alpha-Si(3)N(4) nanobelts by extended vapour
      liquid-solid growth.
AB  - A simple chemical method for the production of single-crystalline alpha-Si(3)N(4)
      nanobelts has been developed, consisting of nitridation of a high-Si-content Fe
      Si 'catalyst' by ammonia at 1300 degrees C. The as-synthesized product was
      characterized by means of x-ray diffraction, electron microscopy and energy
      dispersive x-ray spectroscopy. The alpha-Si(3)N(4) nanobelts have widths of 60
      120 nm, thicknesses of 10-30 nm and lengths up to microns. Four intense green
      blue luminescence bands at 398 nm (3.12 eV), 434 nm (2.86 eV), 492 nm (2.52 eV)
      and 540 nm (2.30 eV) were observed and analysed for the product, which indicates
      the potential applications in optoelectronics. The growth mechanism has also been
      speculated upon. The potential technological importance of the product, the
      simplicity of the preparation procedure, as well as the cheap commercial
      precursor of Fe-Si alloy particles makes this study both scientifically and
      technologically interesting.

PMID- 20818009
TI  - Controlled synthesis and anomalous magnetic properties of relatively monodisperse
      CoO nanocrystals.
AB  - Monodisperse cobalt monoxide (CoO) nanocrystals ranging in size from 4.5 to 23 nm
      were prepared via the thermal decomposition of cobalt acetylacetonate
      (Co(acac)(2)) in oleylamine under vigorous stirring. The size control of the
      nanocrystals was achieved by tailoring the reaction temperature or by seed
      mediated growth. The nanocrystals have been characterized by x-ray diffraction,
      transmission electron microscopy, and Fourier transform infrared and x-ray
      photoelectron spectroscopy. The as-prepared nanocrystals are stable because of
      the organic coating (oleylamine) that occurred in situ. Magnetic measurement
      reveals that all of the nanocrystals are superparamagnetic at high temperatures
      and show ferromagnetic interactions at low temperatures due to the existence of
      uncompensated moments on the surface of the nanoparticles. The weak ferromagnetic
      interactions increase with decreasing particle size.

PMID- 20818010
TI  - A nanofluidic emitter tip obtained by focused ion beam nanofabrication.
AB  - We report here the design, fabrication and testing of a novel nanofluidic device
      which we term a 'nano-nib' due to its resemblance to a nano-fountain pen. The
      nanofluidic device is an emitter tip which incorporates a nanofluidic capillary
      slot coupled to a microfluidic capillary slot. The microfluidic capillary slot is
      fabricated using reactive ion etching (RIE) whilst the nanofluidic capillary slot
      is fabricated using focused ion beam (FIB) etching. The microfluidic capillary
      slot has a length of 2 mm and capillary slot dimensions (w x h) of 1 microm x 4
      microm, i.e. a volume of a few picolitres (pl). The smallest nanofluidic
      capillary slot has a length of 3 microm and capillary slot dimensions as small as
      21 nm x 300 nm, i.e. a volume of a few attolitres (al). Current-voltage
      characterization in electrospray mode revealed a current of 1 nA at an applied
      voltage as low as 40 V. The applications for this nanofluidic device lie in high
      sensitivity electrospray mass spectrometry, direct nanowriting, ultralow volume
      sample extraction/spotting and printing.

PMID- 20818011
TI  - Selective growth of ZnO nanostructures with coordination polymers.
AB  - One-dimensional semiconductor ZnO nanostructures with different morphologies can
      provide different practical and potential applications in a broad field. In this
      paper, a one-dimensional zigzag chain coordination polymer [Zn(4,4(')
      bipy)Cl(2)](n) and a two-dimensional coordination polymer [Formula: see text] are
      successfully promoted to obtain ZnO nanorods and radial nanoneedles on a large
      scale respectively, when they are directly employed as reactants. The different
      frameworks of coordination polymers can build various intermediates in the
      formation process, and the intermediates then mature to different morphologies in
      the final products. The possible formation mechanism and the PL spectra of both
      products are also investigated.

PMID- 20818012
TI  - Friction model for the velocity dependence of nanoscale friction.
AB  - The velocity dependence of nanoscale friction is studied for the first time over
      a wide range of velocities between 1 microm s(-1) and 10 mm s(-1) on large scan
      lengths of 2 and 25 microm. High sliding velocities are achieved by modifying an
      existing commercial atomic force microscope (AFM) setup with a custom calibrated
      nanopositioning piezo stage. The friction and adhesive force dependences on
      velocity are studied on four different sample surfaces, namely dry
      (unlubricated), hydrophilic Si(100); dry, partially hydrophobic diamond-like
      carbon (DLC); a partially hydrophobic self-assembled monolayer (SAM) of
      hexadecanethiol (HDT); and liquid perfluoropolyether lubricant, Z-15. The
      friction force values are seen to reverse beyond a certain critical velocity for
      all the sample surfaces studied. A comprehensive friction model is developed to
      explain the velocity dependence of nanoscale friction, taking into consideration
      the contributions of adhesion at the tip-sample interface, high impact velocity
      related deformation at the contacting asperities and atomic scale stick-slip. A
      molecular spring model is used for explaining the velocity dependence of friction
      force for HDT.

PMID- 20818013
TI  - Progressing single biomolecule force spectroscopy measurements for the screening
      of DNA binding agents.
AB  - Recent studies have indicated that the force-extension properties of single
      molecules of double stranded (ds) DNA are sensitive to the presence of small
      molecule DNA binding agents, and also to their mode of binding. These
      observations raise the possibility of using this approach as a highly sensitive
      tool for the screening of such agents. However, particularly for studies
      employing the atomic force microscope (AFM), several non-trivial barriers hinder
      the progress of this approach to the non-specialist arena and hence also the full
      realization of this possibility. In this paper, we therefore address a series of
      key reproducibility and metrological issues associated with this type of
      measurement. Specifically, we present an improved immobilization method that
      covalently anchors one end (5' end) of a dual labelled (5'-thiol, 3'-biotin) p53
      DNA molecule onto a gold substrate via gold-thiol chemistry, whilst the
      biotinylated 3' end is available for 'pick-up' using a streptavidin modified AFM
      tip. We also show that co-surface immobilization of DNA with 6-mercapto-1-hexanol
      (MCH) can also lead to a further increase the measured contour length. We
      demonstrate the impact of these improved protocols through the observation of the
      cooperative transition plateau in a DNA fragment of approximately 118 bp, a
      significantly smaller fragment than previously investigated. The results of a
      comparative study of the effects of a model minor groove binder (Hoechst 33258)
      and an intercalating drug (proflavine), alone, as a mixture and under different
      buffer conditions, are also presented.

PMID- 20818014
TI  - Novel thermoplastic starch-clay nanocomposite foams.
AB  - Novel thermoplastic starch (TPS)-clay nanocomposite foams were prepared by melt
      processing. The use of urea as plasticizer avoids the cracking of TPS during
      storage and enhances the dispersion of ammonium-treated clay in TPS. X-ray
      diffraction shows an increase in the basal plane spacings of both natural and
      treated clays, suggesting formation of nanocomposites. Scanning electron
      microscopy shows spontaneously formed regular foam structures with 84% porosity
      in TPS-ammonium-treated clay. This does not form in TPS or TPS-natural clay
      nanocomposites. This result implies that the regular foam formation is due to the
      ammonium surfactant of clay, which produces ammonia gas acting as an internal
      blowing agent. Thermogravimetric analysis confirms this deduction.

PMID- 20818015
TI  - Cu nanoparticles derived from CuO electrodes in lithium cells.
AB  - Nanosheet cupric oxide (CuO) was synthesized by a hydrothermal synthesis method
      and its electrochemical performance was tested with Li metal as the reference
      anode. This CuO electrode showed a good capacity retention with a reversible
      capacity of 400 mA h g(-1) during up to 100 cycles. Copper (Cu) nanoparticles
      were produced and separated from the lithiated CuO electrode. Structural analyses
      by means of electron microscopy (field emission scanning electron microscopy and
      transmission electron microscopy) indicated that rather uniform spherical copper
      particles of 30-40 nm were obtained. These copper nanoparticles were collected as
      the lithiation product and this electrochemical reduction method was put forward
      as a new approach for synthesizing metal nanoparticles.

PMID- 20818016
TI  - Catalytic hydride vapour phase epitaxy growth of GaN nanowires.
AB  - Catalytic growth of GaN nanowires by hydride vapour phase epitaxy is
      demonstrated. Nickel-gold was used as a catalyst. Nanowire growth was limited to
      areas patterned with catalyst. Characterization of the nanowires with
      transmission electron microscopy, x-ray diffraction, and low temperature
      photoluminescence shows that the nanowires are stoichiometric 2H-GaN single
      crystals growing in the [0001] orientation when grown on sapphire, with
      occasional stacking faults along the c-axis as the only defect type observed in
      most of the wires. A red shift observed in the photoluminescence was too large to
      be explained by the minor strain observed alone, and was only marginally affected
      by temperature, suggesting a superposition of several factors.

PMID- 20818017
TI  - The bactericidal effect of silver nanoparticles.
AB  - Nanotechnology is expected to open new avenues to fight and prevent disease using
      atomic scale tailoring of materials. Among the most promising nanomaterials with
      antibacterial properties are metallic nanoparticles, which exhibit increased
      chemical activity due to their large surface to volume ratios and
      crystallographic surface structure. The study of bactericidal nanomaterials is
      particularly timely considering the recent increase of new resistant strains of
      bacteria to the most potent antibiotics. This has promoted research in the well
      known activity of silver ions and silver-based compounds, including silver
      nanoparticles. The present work studies the effect of silver nanoparticles in the
      range of 1-100 nm on Gram-negative bacteria using high angle annular dark field
      (HAADF) scanning transmission electron microscopy (STEM). Our results indicate
      that the bactericidal properties of the nanoparticles are size dependent, since
      the only nanoparticles that present a direct interaction with the bacteria
      preferentially have a diameter of approximately 1-10 nm.

PMID- 20818018
TI  - Stabilized and size-tunable gold nanoparticles formed in a quaternary ammonium
      based room-temperature ionic liquid under gamma-irradiation.
AB  - Colloidal gold nanoparticles were synthesized in a quaternary ammonium-based room
      temperature ionic liquid (QAIL) by gamma-radiation for the first time.
      Transmission electron microscopy, x-ray diffraction and optical techniques were
      used to characterize the colloidal nanoparticles. By changing the experimental
      conditions, the size of the gold nanoparticles can be varied between 10 and 50
      nm. It was found that gold nanoparticles coated by QAIL are very stable in
      dispersion.

PMID- 20818019
TI  - Strain mapping in nanowires.
AB  - A method for obtaining detailed two-dimensional strain maps in nanowires and
      related nanoscale structures has been developed. The approach relies on a
      combination of lattice imaging by high-resolution transmission electron
      microscopy and geometric phase analysis of the resulting micrographs using
      Fourier transform routines. We demonstrate the method for a germanium nanowire
      grown epitaxially on Si(111) by obtaining the strain components epsilon(xx),
      epsilon(yy), epsilon(xy), the mean dilatation, and the rotation of the lattice
      planes. The resulting strain maps are demonstrated to allow detailed evaluation
      of the strains and loading on nanowires.

PMID- 20818020
TI  - Templated synthesis of ZnSe nanostructures using lyotropic liquid crystals.
AB  - We report a technique for controlled synthesis of zero-, one-, and two
      dimensional compound semiconductor nanostructures by using cubic, hexagonal, and
      lamellar lyotropic liquid crystals as templates, respectively. The liquid
      crystals were formed by self-assembly in a ternary system consisting of a
      poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) amphiphilic block
      copolymer as the surfactant, heptane as the non-polar dispersed phase, and
      formamide as the polar continuous phase. ZnSe quantum dots and nanowires with
      diameters smaller than 10 nm, as well as free-standing, disc-like quantum wells,
      were grown inside the spherical, cylindrical, and planar nanodomains,
      respectively, by reacting diethylzinc that was dissolved in the heptane domains
      with hydrogen selenide gas that was brought into contact with the liquid crystal
      in a sealed chamber at room temperature and atmospheric pressure. The shape and
      size of the resulting nanostructures can be manipulated by selecting the
      templating phase of the liquid crystal, the size of the dispersed nanodomains
      that is controlled by the composition of the template, and the concentration of
      diethylzinc in them.

PMID- 20818021
TI  - Controlling PbS nanocrystal aggregation in conducting polymers.
AB  - PbS nanocrystals were synthesized directly in the conducting polymer, poly(3
      hexylthiophene-2,5-diyl). Transmission electron microscopy shows that the PbS
      nanocrystals are faceted and relatively uniform in size with a mean size of 10
      nm. FFT analysis of the atomic lattice planes observed in TEM and selected area
      electron diffraction confirm that the nanocrystals have the PbS rock salt
      structure. The synthesis conditions are explored to show control over the
      aggregation of PbS nanocrystals in the thiophene conducting polymer.

PMID- 20818022
TI  - The effects of gamma-irradiation dose on chemical modification of multi-walled
      carbon nanotubes.
AB  - Multi-walled carbon nanotubes (MWNTs) irradiated with gamma-rays were subjected
      to chemical modification with thionyl chloride and decylamine. Products from
      chemical treatment were characterized by both FTIR and Raman spectra. Element
      analysis (EA) and thermogravimetric analysis (TGA) for the modified soluble MWNTs
      (s-MWNTs) indicated that gamma-radiation increased the concentration of
      functional groups bound to MWNTs, which arose due to the increasing number of
      defect sites created on the MWNTs by gamma-photons. Compared with untreated
      MWNTs, gamma-irradiation significantly enhanced the solubility of MWNTs in
      acetone and tetrahydrofuran (THF). We therefore conclude that gamma-irradiation
      provides a novel approach to prepare various functionalized modifications of
      carbon nanotubes (CNTs).

PMID- 20818023
TI  - Tunable growth of TiO(2) nanostructures on Ti substrates.
AB  - A simple and facile method is described to directly synthesize TiO(2)
      nanostructures on titanium substrates by oxidizing Ti foil using small organic
      molecules as the oxygen source. The effect of reaction temperature and oxygen
      source on the formation of the TiO(2) nanostructures has been studied using
      scanning electron microscopy, x-ray diffraction, transmission electron
      microscopy, Raman spectroscopy and water contact angle measurement.
      Polycrystalline grains are formed when pure oxygen and formic acid are used as
      the oxygen source; elongated micro-crystals are produced when water vapour is
      used as the oxygen source; oriented and aligned TiO(2) nanorod arrays are
      synthesized when ethanol, acetaldehyde or acetone are used as the oxygen source.
      The growth mechanism of the TiO(2) nanostructures is discussed. The diffusion of
      Ti atoms to the oxide/gas interface via the network of the grain boundaries of
      the thin oxide layer is the determining factor for the formation of well-aligned
      TiO(2) nanorod arrays. The wetting properties of the TiO(2) nanostructured
      surfaces formed are dictated by their structure, varying from a hydrophilic
      surface to a strongly hydrophobic surface as the surface structure changes from
      polycrystalline grains to well-aligned nanorod arrays. This tunable growth of
      TiO(2) nanostructures is desirable for promising applications of TiO(2)
      nanostructures in the development of optical devices, sensors, photo-catalysts
      and self-cleaning coatings.

PMID- 20818024
TI  - A 3D view on free-floating, space-fixed and surface-bound para-phenylene
      nanofibres.
AB  - Nanofibres from para-hexaphenylene and functionalized quaterphenylene molecules
      are grown on mica surfaces and are thereafter transferred into solution, where
      they either freely rotate in water or are space-fixed in sucrose. From freely
      rotating aggregates highly anisotropic angular intensity distributions of emitted
      light for individual aggregates are determined. Luminescence is enhanced at the
      nanofibre tip as compared to the broad side by about an order of magnitude
      probably due to waveguiding along the long axis of the aggregates. For dense
      arrays of nanofibres on mica the increase of emitted intensity towards the
      substrate plane in the direction of the long axes of the nanofibres is smaller
      and it depends on the effective thickness of the nanofibre films. The difference
      between individual aggregates and aggregate arrays is interpreted in terms of
      light scattering at surface roughness inside the nanofibre film and on the border
      of the underlying mica substrate. Aggregates fixed in solution, with the help of
      femtosecond laser scanning microscopy, allow us to obtain two-photon absorption
      spectra of functionalized nanofibres between 720 and 900 nm as well as
      morphological features from three-dimensional optical images. The lateral
      resolution is about 400 nm.

PMID- 20818025
TI  - Surface crystallization effects on the optical and electric properties of CdS
      nanorods.
AB  - We synthesized CdS nanorods through a conventional solvothermal method and
      studied their photoluminescence and electric transport properties before and
      after annealing. High-resolution transmission electron microscopy indicated that
      the surface layer of the annealed CdS nanorods was well crystallized, while that
      of the unannealed nanorods was amorphous. Energy-dispersive x-ray spectrography,
      x-ray photoelectron spectrography and thermogravimetric analysis were used to
      demonstrate that the amorphous layer at the surface of the as-prepared nanorods
      was pure CdS. The photoluminescence spectra showed that after annealing the
      intensity of the band-edge emission increased several times and the surface state
      emission at 548 nm disappeared. The unannealed CdS nanorods had approximately
      linear I-V characteristics and the conductance suddenly increased about 100 times
      upon visible light illumination by a halogen lamp. The annealed CdS nanorods
      exhibited nonlinear conductance with a turn-on voltage at about 2.2 V. These
      properties show that CdS nanorods have potential applications in
      nanophotoelectric or sensing devices.

PMID- 20818026
TI  - Synthesis of MnWO(4) nanofibres by a surfactant-assisted complexation
      precipitation approach and control of morphology.
AB  - Single-crystal MnWO(4) nanofibres with diameters as small as 3-4 nm and length up
      to 800-1000 nm have been successfully synthesized by a novel surfactant-assisted
      complexation-precipitation method. X-ray powder diffraction (XRD), transmission
      electron microscopy (TEM), high-resolution transmission electron microscopy
      (HRTEM), and electron diffraction (ED) were employed to study the crystal
      structure and morphologies of the products. Experiments show that the
      complexation and the surfactant are the crucial factors affecting the morphology
      of the products. The possible formation process and growth mechanism have been
      proposed.

PMID- 20818027
TI  - Shape-controlled synthesis of silver nanostructures.
AB  - At room temperature, without any template and in the solid phase, shape
      controlled silver nanostructures are synthesized using solid electrolyte
      RbAg(4)I(5) thin film under direct current electric field (DCEF) treatment. With
      different DCEF strengths, we have synthesized silver single-crystalline
      nanowires, nanotubes, nanoparticles and nanoframes. The growth mechanism and the
      relationship between the DCEF strength and the synthesized nanostructures are
      discussed briefly.

PMID- 20818028
TI  - Low temperature micelle-template assisted growth of Bi(2)S(3) nanotubes.
AB  - The growth of Bi(2)S(3) nanotubes through a simple soft chemical route using the
      surfactant Triton-X 100 as the template at the relatively very low temperature of
      115 degrees C/12 h has been reported for the first time. These nanotubes are
      nearly uniform in dimensions, with diameter around 120 nm and length up to 8
      microm, their nature being single crystalline. The reaction conditions are
      optimized. Development of nanotubes and nanoparticles from the same precursor is
      discussed. The optical properties of the nanotubes are studied by means of UV
      visible and photoluminescence spectra. The band gap calculated from the
      absorption spectra is found to be 1.76 eV, indicating a considerable blue shift
      relative to the bulk.

PMID- 20818029
TI  - Fabrication of nanostructures of polyethylene glycol for applications to protein
      adsorption and cell adhesion.
AB  - A simple method was developed to fabricate polyethylene glycol (PEG)
      nanostructures using capillary lithography mediated by ultraviolet (UV) exposure.
      Acrylate-containing PEG monomers, such as PEG dimethacrylate (PEG-DMA, MW = 330),
      were photo-cross-linked under UV exposure to generate patterned structures. In
      comparison to unpatterned PEG films, hydrophobicity of PEG nanostructure modified
      surfaces was significantly enhanced. This could be attributed to trapped air in
      the nanostructures as supported by water contact angle measurements. Proteins
      (fibronectin, immunoglobulin, and albumin) and cells (fibroblasts and P19 EC
      cells) were examined on the modified surfaces to test for the level of protein
      adsorption and cell adhesion. It was found that proteins and cells preferred to
      adhere on nanostructured PEG surfaces in comparison to unpatterned PEG films;
      however, this level of adhesion was significantly lower than that of glass
      controls. These results suggest that capillary lithography can be used to
      fabricate PEG nanostructures capable of modifying protein and cell adhesive
      properties of surfaces.

PMID- 20818030
TI  - The equilibrium geometry and electronic structure of Bi nanolines on clean and
      hydrogenated Si(001) surfaces.
AB  - The equilibrium geometry, electronic structure and energetic stability of Bi
      nanolines on clean and hydrogenated Si(001) surfaces have been examined by means
      of ab initio total energy calculations and scanning tunnelling microscopy. For
      the Bi nanolines on a clean Si surface the two most plausible structural models,
      the Miki or M model (Miki et al 1999 Phys. Rev. B 59 14868) and the Haiku or H
      model (Owen et al 2002 Phys. Rev. Lett. 88 226104), have been examined in detail.
      The results of the total energy calculations support the stability of the H model
      over the M model, in agreement with previous theoretical results. For Bi
      nanolines on the hydrogenated Si(001) surface, we find that an atomic
      configuration derived from the H model is also more stable than an atomic
      configuration derived from the M model. However, the energetically less stable
      (M) model exhibits better agreement with experimental measurements for
      equilibrium geometry. The electronic structures of the H and M models are very
      similar. Both models exhibit a semiconducting character, with the highest
      occupied Bi-derived bands lying at approximately 0.5 eV below the valence band
      maximum. Simulated and experimental STM images confirm that at a low negative
      bias the Bi lines exhibit an 'antiwire' property for both structural models.

PMID- 20818031
TI  - Inkjet printing of nanosized silver colloids.
AB  - A water-based conducting ink, composed of well dispersed nano-silver particles,
      has been successfully inkjet printed using an ordinary commercial printer. The
      silver colloids with diameter around 50 nm were dispersed in a water and
      diethylene glycol cosolvent system. The 25 wt% silver ink had a viscosity of
      about 7.4 cP and surface tension of 33.5 dyn cm(-1) at 20 degrees C, which is
      appropriate for printing jobs. Continuous and smooth lines of 130 microm width
      could be printed on ordinary glass substrates using an Epson R210 printer. After
      baking at 260 degrees C for 3 min, these lines exhibited a resistivity of 1.6 x
      10(-5) Omega cm, which could serve as conducting lines for electronic
      applications.

PMID- 20818032
TI  - Carbon nanotubes grow to pillars.
AB  - In this paper, we report on the self-assembly growth of micro-pillars consisting
      of well-aligned carbon nanotubes on the uneven surfaces of silicon chips by
      chemical vapour deposition, which could be useful for the fabrication of electron
      field emitters, micro-electromechanical devices, interconnection for
      microelectronics, etc. The mechanism for the growth of isolated pillars within
      large-area aligned carbon nanotube arrays is also discussed.

PMID- 20818033
TI  - The use of etched registration markers to make four-terminal electrical contacts
      to STM-patterned nanostructures.
AB  - We demonstrate the use of etched registration markers for the alignment of four
      terminal ex situ macroscopic contacts created by conventional optical lithography
      to buried nanoscale Si:P devices, patterned by hydrogen-based scanning tunnelling
      microscope (STM) lithography. Using SiO(2) as a mask we are able to protect the
      silicon surface from contamination during marker fabrication and can achieve
      atomically flat surfaces with atomic-resolution imaging. The registration markers
      are shown to withstand substrate heating to approximately 1200 degrees C and
      epitaxial overgrowth of approximately 25 nm Si. Using a scanning electron
      microscope to position the STM tip with respect to the markers, we can achieve
      alignment accuracies of approximately 100 nm, which allows us to contact buried
      Si:P structures. We have applied this technique to fabricate P-doped wires of
      different widths and measured their I-V characteristics at 4 K, finding ohmic
      behaviour down to a width of approximately 27 nm.

PMID- 20818034
TI  - In situ templated synthesis of anatase single-crystal nanotube arrays.
AB  - Anatase single-crystal nanotubes were obtained using an in situ templated method.
      First, highly ordered titania arrays were formed through an anodization process
      in H(3)PO(4) electrolytes containing 0.5 wt% HF. Under optimized conditions
      titania nanotubes with a diameter of up to 100 nm and a length of up to 1.1
      microm were prepared. Second, the crystallization and stability of the titania
      nanotubes were studied in air at elevated temperatures. Anatase single-crystal
      nanotubes were fabricated after annealing the sample in air at 450 degrees C. The
      anatase single-crystal structure was verified by selected area diffraction
      pattern and HRTEM images.

PMID- 20818035
TI  - Growth behaviour of well-aligned ZnO nanowires on a Si substrate at low
      temperature and their optical properties.
AB  - Well-aligned ZnO nanowires were successfully synthesized on a silicon substrate
      at the low temperature of 550 degrees C by catalyst-free vapour phase deposition.
      The ZnO nanowires had diameters in the range of 70-100 nm and lengths over
      several tens of micrometres. The synthesized ZnO nanowires, which had a single
      crystalline wurtzite structure, showed a uniform morphology and faceted planes at
      the tips of the nanowires. The photoluminescence of the ZnO nanowires showed a
      strong UV band at 3.28 eV and a broad green band at 2.29 and at 2.53 eV at room
      temperature. A detailed discussion regarding the growth behaviour and the growth
      mechanism of the ZnO nanowires on the silicon substrate is presented in this
      work.

PMID- 20818036
TI  - Flower-shaped ZnO nanostructures obtained by cyclic feeding chemical vapour
      deposition: structural and optical properties.
AB  - Flower-shaped ZnO nanostructures were grown on Si(100) and Si(111) substrates by
      cyclic feeding chemical vapour deposition without the use of a metal catalyst.
      The structures obtained on the Si(100) substrate exhibited triangle-shaped leaves
      with lengths and diameters in the ranges 300-400 and 90-130 nm, respectively.
      Uniformly shaped leaves with hexagonal facets originating from one centre were
      observed on the flower-shaped structures grown on the Si(111) substrate.
      Transmission electron microscopy and selected area electron diffraction patterns
      showed that these structures are highly crystalline, with the wurtzite hexagonal
      phase, and preferentially oriented in the c-axis direction. Unlike star-shaped
      ZnO nanostructures grown on Au-coated silicon substrates, the flower-shaped
      nanostructures showed sharp and strong UV emission at 378 nm and broad and weak
      green emission at 520 nm, indicating a good crystal quality and few structural
      defects.

PMID- 20818037
TI  - Nitrification/denitrification in swine wastewater using porous ceramic sticks
      with plastic rings as supporting media in two-stage fixed-biofilm reactors.
AB  - This study evaluated the performance of oxic-anoxic fixed-biofilm reactors (FBRs)
      using porous ceramic sticks with plastic rings as supporting media for nitrogen
      and organic carbon (as COD) removal from swine wastewater. Experimental results
      indicate that the removal efficiency of NH(4)(+)-N increased to 86-92% from 52
      98% as the volumetric ammonium-nitrogen loading rate increased to 0.25 kg
      NH(4)(+)-N/m(3)-d from 0.082 kg NH(4)(+)-N/m(3)-d. Furthermore, during the
      denitrifying column test, the average removal efficiencies for COD and NO(x)-N
      were 83 and 76%, respectively. Only small amounts of NO(2)(-)-N and NO(3)(-)-N
      accumulated in the denitrifying FBR. The average values for NO(2)(-)-N and NO(3)(
      )-N in effluent from denitrifying reactor were roughly 2 mg/L and 6 mg/L,
      respectively. Approximately 82% of NO(3)(-)-N was converted into N(2) by
      denitrifying bacteria in the denitrifying FBR. Approximately 98-100% high removal
      efficiencies of NO(x)-N could be reached in denitrifying FBR, when the ratio of
      COD(r)/NO(x)-N(r) was controlled at 9-12 throughout the test. Microscopic
      observations show that cell number on the ceramic sticks in denitrifying FBR was
      greater than that in nitrifying FBR in the final phase of colonization.

PMID- 20818038
TI  - Operating costs for reducing total emission loads of key pollutants in municipal
      wastewater treatment plants in China.
AB  - Total emission load reduction of COD, NH(4)-N, TN, and TP is the key measure in
      controlling water pollution and eutrophication. Municipal wastewater treatment
      plants (MWWTPs) are major contributors in lowering energy consumption and
      reducing pollutant discharge. The flow-based operating costs have not been
      directly established to relate to costs of pollutant reduction based on an
      investigation of 11 MWWTPs in China. However, energy consumption to eliminate one
      kilogram of COD or NH(4)-N was observed to decrease when the total reduced
      pollutants is increased. Additional energy consumption required to remove
      nitrogen and phosphorus is allotted for mixers and internal return pumps. Major
      factors for operating costs include influent and effluent concentration, design
      capacity, and flow loading rate. Therefore, an operating cost model for the total
      emission load reduction of COD, NH(4)-N, TN, and TP was developed based on energy
      consumption and the above mentioned major factors. Using this model to calculate
      the operating costs for MWWTPs would facilitate more reduction of key pollutants
      than the flow-based method.

PMID- 20818039
TI  - Effects of open water on the performance of a constructed wetland for nonpoint
      source pollution control.
AB  - The seasonal performance of four differently configured constructed wetland
      systems was compared for the treatment efficiency of nonpoint source pollution.
      Dead plants in the constructed wetlands increased the nitrogen removal rate
      during winter by providing organic carbon, which is essential for the
      denitrification process. However, when the wetlands released phosphorus from the
      dead plants, the removal rate of phosphorus decreased. After seven growing
      seasons, plant coverage was nearly 100%, and the dissolved oxygen (DO)
      concentration was lowered to 1.3-5.4 mg/L. Open-water sections were then
      constructed inside the wetlands, which resulted in enhanced DO concentrations as
      well as improved treatment efficiency of nutrients and biochemical oxygen demand
      (BOD). Overall, performance of the constructed wetland was improved BOD, total
      nitrogen, and total phosphorus with the establishment of open water sections in
      the constructed wetland system.

PMID- 20818040
TI  - Automatic, semi-automatic and manual validation of urban drainage data.
AB  - Advances in sensor technology and the possibility of automated long distance data
      transmission have made continuous measurements the preferable way of monitoring
      urban drainage processes. Usually, the collected data have to be processed by an
      expert in order to detect and mark the wrong data, remove them and replace them
      with interpolated data. In general, the first step in detecting the wrong,
      anomaly data is called the data quality assessment or data validation. Data
      validation consists of three parts: data preparation, validation scores
      generation and scores interpretation. This paper will present the overall
      framework for the data quality improvement system, suitable for automatic, semi
      automatic or manual operation. The first two steps of the validation process are
      explained in more detail, using several validation methods on the same set of
      real-case data from the Belgrade sewer system. The final part of the validation
      process, which is the scores interpretation, needs to be further investigated on
      the developed system.

PMID- 20818041
TI  - Effect of active control of electric potential of filter medium on depth
      filtration.
AB  - The effect of active control of electric potential of filter medium on depth
      filtration was explored experimentally. Activated carbon particles were selected
      as the conductive filter medium. The filter medium potential was controlled with
      an external DC power supply. Kaolin particles were used as the model suspended
      solid. The activated carbon and kaolin had negative zeta potential around neutral
      pH. When the filter medium potential against a counter electrode was greater than
      or equal to + 0.2 V, rejection rate of particles was 1.8 times higher than that
      when the potential was less than + 0.2 V. Thus adsorption of particles by
      interaction of electric double layers was enhanced by maintaining a positive
      charge on the filter media. Desorption of kaolin trapped on the filter media was
      also confirmed by changing the filter medium potential from positive to negative.
      The percentage of kaolin particles desorbed was 11% of the kaolin trapped on the
      filter media. The desorption rate was not high, but this technique will enhance
      refreshment of the filter media when combined with back washing.

PMID- 20818042
TI  - Evaluation of community participation in the implementation of community-based
      sanitation systems: a case study from Indonesia.
AB  - Acceptance and adequate use of water and sanitation technologies in least
      developed countries is still a chimera, with one billion people using unimproved
      water supply sources and 2.5 billion not benefitting from adequate sanitation.
      Public participation in water and sanitation planning and pre-implementation
      phases has become increasingly important for technology providers seeking
      solutions to implementation challenges towards the achievement of the Millennium
      Development Goals (MDGs). Based on the principle that successful implementation
      of WATSAN technologies ultimately depends on recipients' ability to absorb a
      technology and adapt it to their own needs, this study analyses the impacts of
      participatory methods adopted by community-based sanitation (CBS) providers on
      communities' receptivity of the transferred systems. A fieldwork activity was
      undertaken in Indonesia and a multiple case study approach adopted to analyse
      indicators of receptivity of the transferred technologies. Conclusions show that
      community involvement through participatory methods in the implementation of CBS
      systems can enhance the process of acceptance and management of the technologies,
      thereby increasing the progress towards the achievement of the Millennium
      Development Goals.

PMID- 20818043
TI  - The influence of trace NO(2) on the kinetics of ammonia oxidation and the
      characteristics of nitrogen removal from wastewater.
AB  - Ammonia oxidizing bacteria-enriched sludge was obtained in a sequencing batch
      reactor with synthetic wastewater. Batch tests of ammonia oxidation were carried
      out with the sludge, in the presence of only trace NO(2) and in the presence of
      O(2) and trace NO(2), respectively. The Andrews model is used to describe NO(2)
      dependent ammonia oxidation. The maximum ammonia oxidation rate of 139.11 mg N.(g
      sludge COD h)(-1), occurred in the presence of 21% O(2) and 100 ppm NO(2), which
      was 3 times higher than the aerobic ammonia oxidation rate without NO(2). The
      kinetic model of ammonia oxidation in the presence of O(2) and trace NO(2) is
      developed, and the function of NO(2) apparently enhancing ammonia oxidation is
      suggested. The maximal nitrogen removel of 34.19% occurred at the 21% O(2) and
      100 ppm NO(2) in the mixed gases. Nitrogen removal principally depended on the
      denitrification activity and NO(2)-dependent ammonia oxidation activity of
      ammonia-oxidizing bacteria (AOB).

PMID- 20818044
TI  - A new operation mode solving clogging problems of horizontal subsurface
      constructed wetlands.
AB  - Horizontal subsurface constructed wetland (SSFCW) has been widely used to treat
      wastewater, however the capacity of SSFCW is severely confined by clogging
      problems which are very common during the lifespan of a SSFCW. Therefore it is of
      great practical significance to improve the performance of SSFCW. In this study,
      a new operation mode by changing the flow direction periodically was executed and
      the performance on the pollutants removal was studied. Three years' experimental
      results showed that the SSFCW with new operation mode achieved better pollutant
      removal efficiency compared with the performance obtained under traditional
      operation mode. The microorganism test showed that the reciprocating SSFCW had
      larger quantity microorganism which effectively prevented organic compounds
      accumulation. The readings of gauge glass in the traditional SSFCW rose
      gradually, while the water level kept stable in reciprocating one, which also
      reflected the severity of the clogging problem in the two wetlands. During the
      whole operation period, the SSFCW with reciprocating operation mode didn't have
      any infiltration problem, while SSFCW with traditional operation mode had visible
      clogging problems as a result of pollutants accumulation in the inlet zone.

PMID- 20818045
TI  - Phenol biodegradation and simultaneous nitrogen removal using a carbon fiber felt
      biofilm reactor.
AB  - Phenol biodegradation and its effect on the biological nitrogen removal were
      studied in a biofilm reactor (15 L) packed with carbon fiber felt carriers.
      Meanwhile, the effects of the effluent internal recirculation ratios (0, 100% and
      200%) and the air flow rates (0.42, 0.83, 1.46, 2.08 and 3.33 L/min) on the
      performance of system were tested. The system exhibited an excellent capacity for
      simultaneous phenol biodegradation and biological nitrogen removal without
      effluent internal recirculation when the influent phenol concentration was as
      high as 1,000 mg/L (organic loading rate of 9.54 kg COD/(m(3) d)) and the ammonia
      loading rates of 0.20, 0.32 and 0.40 kg NH(4)(+)-N/(m(3) d) respectively).
      Nitrification process was inhibited at the influent phenol concentration of 1,200
      1,300 mg/L with average ammonia removal efficiency of 26.9%. The nitrifiers
      activity could be recovered in the perfect performance of system for phenol
      biodegradation. However, denitrification was not affected by the process of
      phenol biodegradation. In the air flow rates of 1.46-2.08 L/min, the system
      manifested stable operation for phenol elimination and nitrogen removal.
      Dissolved oxygen (DO) distributions in carbon fiber felt biofilm descended
      gradually from the external to the center of the carrier in all air flow rates.

PMID- 20818046
TI  - Liquid-phase non-thermal plasma-prepared N-doped TiO(2) for azo dye degradation
      with the catalyst separation system by ceramic membranes.
AB  - This study strived to improve the photocatalytic activity by using liquid-phase
      non-thermal plasma (LPNTP) technology for preparing N-doping TiO(2) as well as to
      separate/recover the N-dope TiO(2) particles by using ceramic ultrafiltration
      membrane process. The yellow color N-doped TiO(2) photocatalysts, obtained
      through the LPNTP process, were characterized with UV-Vis spectroscopy, X-ray
      diffraction (XRD), and electron spectroscopy for chemical analysis (ESCA). The UV
      Vis spectrum of N-doped TiO(2) showed that the absorption band was shifted to 439
      nm and the band gap was reduced to 2.82 eV. The structure analysis of XRD spectra
      showed that the peak positions and the crystal structure remained unchanged as
      anatase after plasma-treating at 13.5 W for 40 min. The photocatalytic activity
      of N-doped TiO(2) was evaluated by azo dyes under visible light, and 63% of them
      was degraded after 16 hours in a continuous-flow photocatalytic system. For
      membrane separation/recover system, the recovery efficiency reached 99.5% after
      the ultrafiltration had been carried out for 90 min, and the result indicated
      that the photocatalyst was able to be separated/recovered completely.

PMID- 20818047
TI  - A comparative study of the pollution status of Sakumo II and Muni lagoons in
      Ghana.
AB  - The pollution status of Sakumo II and Muni Lagoons and Mamahuma and Gbagbla
      Ankonu feeder streams, which feed Sakumo II along the coast of Ghana, were
      assessed and compared. As expected of saline waters, pH values of both lagoons
      fell within a slightly neutral to saline range whilst, the feeder streams were
      moderately saline. Conductivity distribution also showed saline (>5.0 mS cm(-1))
      characteristics of the lagoons, while, the feeder streams are brackish (1.5-5.0
      mS cm(-1)). DO concentrations in both lagoons indicated a wide variation.
      Relatively high BOD and nutrients content of Sakumo II and the feeder streams
      suggested that, Sakumo II and its feeder streams are moderately to grossly
      polluted. However, Muni Lagoon was characterized by relatively low BOD and
      nutrients content suggesting relatively low anthropogenic impact. The ionic
      dominance patterns for Sakumo II and Muni Lagoons were: Na(+) > Mg(2 + ) > Ca(2 +
      ) and Cl(-) > HCO(3)(-) > SO(4)(2-), Na(+) > Ca(2 + ) > Mg(2 + ) and Cl(-) >
      HCO(3)(-) > SO(4)(2-), respectively. Using water quality index (WQI), Sakumo II
      was found to be grossly polluted and requires mitigation measures, while, Muni
      Lagoon was of fairly good quality and requires monitoring.

PMID- 20818048
TI  - Oxidation of nitrobenzene by ozone in the presence of faujasite zeolite in a
      continuous flow gas-liquid-solid reactor.
AB  - This work investigates the oxidation of nitrobenzene (NB) by ozone in the
      presence of faujasite zeolite. Experiments were carried out in a gas-liquid-solid
      reactor were ozone transfer and NB oxidation took place at the same time. Three
      configurations of the reactor were compared: empty, filled with inert glass beads
      and filled with faujasite pellets. First, ozone transfer coefficient (k(L)a) and
      decomposition rate constant (k(C)) were determined for each configuration. In
      presence of solid, k(L)a was 2.0 to 2.6 times higher and k(C) was 5.0 to 6.4
      times higher compared to the empty reactor. Then, the various configurations were
      evaluated in terms of NB removal and chemical oxygen demand (COD) decrease. The
      faujasite reactor showed higher removal of NB and decrease of COD compared to
      other configurations under the same conditions suggesting that the faujasite
      increases the oxidation rate of NB. Oxidation of NB in presence of faujasite also
      proved to be limited by the transfer of ozone from the gas to the liquid phase.

PMID- 20818049
TI  - Elimination of selected pharmaceuticals by biosolids from municipal wastewater
      treatment plants: importance of modest pH change and degree of mineralization.
AB  - Lab-scale batch experiments with biosolids collected from a full-scale activated
      sludge system (AS) and a pilot-scale membrane bioreactor (MBR) were carried out
      to investigate the mechanisms of elimination of 5 acidic pharmaceuticals and 2
      neutral pharmaceuticals. Batch elimination experiments were conducted under the
      conditions of pH of 6 and 7, and a great impact of pH on elimination of
      pharmaceuticals was shown by the significant differences in elimination rates
      under different pH conditions: elimination of pharmaceuticals was enhanced under
      the condition of lower pH regardless of the type of biosolid. Degree of
      mineralization of ibuprofen was also investigated in this study by using (14)C
      labeled compounds. Although ibuprofen has been considered to be a readily
      biodegradable pharmaceutical in previous studies, the results obtained in this
      study demonstrated that the degree of mineralization of ibuprofen would be
      limited in biological wastewater treatment including MBRs. The results obtained
      in this study imply that a large portion of pharmaceuticals that have been
      considered "biodegradable", such as ibuprofen, entering into wastewater treatment
      plants will eventually be discharged into natural water bodies as intermediates,
      although concentrations of them may look reduced on the basis of common
      analytical methods (i.e. GC/MS or LC/MS/MS).

PMID- 20818050
TI  - An agent-based approach for generating virtual sewer systems.
AB  - The application of artificial case studies is a well established technique in
      urban drainage to test measures, approaches or models. However, the preparation
      of a virtual case study for a sewer system is a tedious task. Several algorithms
      have been presented in the literature for an automatic generation of virtual
      sewer systems. Applying the approach of generating virtual cities by means of the
      software VIBe (Virtual Infrastructure Benchmarking) the urban structure
      (including elevation map, land use and population distribution) is generated
      firstly and the infrastructure is designed meeting the requirements of the urban
      structure. The aim of this paper is the development of an agent based approach
      for generating virtual sewer systems. This new algorithm functions as module of
      the software VIBe but can of course also be applied to a real city in order to
      get information on possible/optimal sewer placement. Here hundred virtual VIBe
      cities and for each twelve virtual sewer networks are generated and calibrated
      based on data of an alpine region. It is revealed that with the approach
      presented virtual sewer networks which are comparable with real world sewer
      networks can be generated. The agent based method provides data sets for
      benchmarking and allows case independent testing of new measures.

PMID- 20818051
TI  - Pesticide inputs from the sewage treatment plant of Agrinio to River Acheloos,
      western Greece: occurrence and removal.
AB  - This work reports the occurrence and the removal of a wide spectrum of pesticides
      in municipal wastewaters from the Agrinio region, Greece. Analytical
      determination was carried out by means of solid-phase extraction followed by gas
      chromatography equipped with flame thermionic and mass spectrometric detection.
      The herbicides atrazine, alachlor, isoproturon, and s-metolachlor and the
      insecticides diazinon, methidathion, fenthion and chlorpyriphos, were more
      frequently detected in influent and effluent samples while they were also
      detected in river samples. Isoproturon and diazinon showed the highest
      concentrations in influent samples that reached concentrations up to 2,328 and
      1,486 ng L(-1), respectively. Secondary treatment and cumulative removal rates
      for herbicides and insecticides ranged between 23-91%, 21->99% and 36->99%, 38
      >99%, respectively. The data demonstrate that there are significant levels of
      pesticides entering river waterways.

PMID- 20818052
TI  - Performance of Moringa oliefera as a biosorbent for chromium removal.
AB  - This study investigated adsorption of chromium on to a bio-adsorbent, Moringa
      oleifera seed. Different by-products of the seed processing were used as
      adsorbents. These include: the Whole Seed Powder (WSP), the Residue after
      Coagulant Extraction (RaCE) and an Activated Carbon (AC) prepared from the seed
      husk. Adsorption studies for the removal of Cr(III) and Cr(VI) were carried out
      in batch experiments and the effects of adsorbent dosage, contact time, pH and
      initial chromium concentration were analysed. Experimental results showed that
      maximum removal of Cr(III) and Cr(VI) was observed at pH 7 and pH 2,
      respectively. The percentage removals of Cr(III) by WSP, RaCE and AC were: 97, 94
      and 99.9%, respectively. And the percentage removals of Cr(VI) by RaCE and AC
      were 47 and 83.2%, respectively. RaCE showed similar adsorption capacity to the
      WSP, which indicates that it is possible to extract a coagulant and use the waste
      product for adsorption. By using the RaCE, residual dissolved organic carbon in
      the treated water was significantly reduced compared to using the WSP. These
      results indicate that biomaterials can be considered as potential adsorbents for
      heavy metals removal from water or wastewater systems.

PMID- 20818053
TI  - Photocatalytic decolorisation and mineralisation of orange dyes on immobilised
      titanium dioxide nanoparticles.
AB  - In this paper the photocatalytic decolorisation and mineralisation of three
      orange dyes (AO10, AO12 and AO8) in neutral, alkaline and hydrolysed solutions
      under UV light irradiation in the presence of TiO(2) nanoparticles has been
      compared. The investigated photocatalyst was Millennium PC-500 TiO(2)
      (crystallites mean size 5-10 nm) immobilised on non-woven paper. All the
      experiments were performed in a circulation photochemical reactor equipped with a
      15 W UV lamp emitting around 365 nm. Results indicated that complete
      decolorisation of 250 mL pure dye solutions with initial dye concentration of 30
      mg/L could be achieved in 140 min. Photocatalytic mineralisation of the neutral,
      alkaline and hydrolysed dye solutions was monitored by total organic carbon (TOC)
      decrease and ammonium ion formation. Results indicated that the photocatalytic
      decolorisation and mineralisation of the dyes was less efficient with the
      hydrolysed and alkaline dye solutions in comparison with the neutral pure dye
      solutions. The amount of NH(4)(+), as N-containing mineralisation product, during
      UV/TiO(2) process was analysed. The electrical energy consumption for
      photocatalytic decolorisation of the dyes was calculated and related to the
      treatment costs.

PMID- 20818054
TI  - Membrane filtration of municipal wastewater effluents for implementing
      agricultural reuse in southern Italy.
AB  - Membrane filtration was investigated at field scale in order to assess its
      effectiveness for reusing municipal effluents in agriculture. The study was
      started on April 2002 and ended on September 2007, as part of a national R&D
      project (AQUATEC). Preliminary results, which we already reported elsewhere,
      concerned the first two project years while this paper refers to the subsequent
      period. Three different crops (processing tomato, fennel and lettuce) were grown
      in rotation at a test field located in Apulia (Southern Italy) and irrigated with
      membrane filtered municipal secondary effluents. The quality of the reclaimed
      water was monitored chemically and microbiologically, and compared with
      conventional water pumped from a local well. Both water sources were used in
      parallel for irrigating two plots of the test field. The results showed that the
      microbiological quality of the treated wastewater was comparable to or even
      higher than that of the conventional source. Protozoan (oo)cysts were
      experimentally identified as effective indicators of possible failures of the
      filtration system. Moreover, long term heavy metals accumulation trends were
      monitored in soil and crops, showing that despite some lead and copper
      accumulation in the soil, no measurable increase of these metals was observed in
      the edible parts of the crops.

PMID- 20818055
TI  - Oil droplets and solid particles removal using circular separator with inclined
      coalescence mediums: comparison between co-current and counter-current flow.
AB  - This research investigated the effects of co- and counter-current flow patterns
      on oil-water-solid separation efficiencies of a circular separator with inclined
      coalescence mediums. Oil-water-solid separations were tested at different
      influent concentrations and flowrates. Removal efficiencies increased as influent
      flowrate decreased, and their correlationship can be represented by power
      equations. These equations were used to predict the required flowrate, Q(ss50),
      for a given influent suspended solids concentration C(iss) to achieve the desired
      effluent suspended solids concentration, C(ess) of 50 mg/L, to meet environmental
      discharge requirements. The circular separator with counter-current flow was
      found to attend removal efficiencies relatively higher as compared to the co
      current flow. As compared with co-current flow, counter-current flow Q(ss50) was
      approximately 1.65 times higher than co-current flow. It also recorded 13.16%
      higher oil removal at influent oil concentration, C(io) of 100 mg/L, and
      approximately 5.89% higher TSS removal at all influent flowrates. Counter-current
      flow's better removal performances were due to its higher coalescing area and
      constant interval between coalescence plate layers.

PMID- 20818056
TI  - Diffusion models for adsorption kinetics of Zn(2+ ), Cd(2+ ) and Pb(2+ ) onto
      natural zeolite.
AB  - The kinetics of zinc, cadmium, and lead ions removal by natural zeolite
      clinoptilolite has been investigated using an agitated batch adsorber. Batch
      experiments at constant temperature have been performed. The influence of
      agitation speed, initial heavy metals concentration and particle size of the
      sorbent on the removal efficiency of heavy metals from liquid phase have been
      studied. A decrease in the initial heavy metals concentration in aqueous
      solutions prolongs the time needed for equilibrium. Two kinetics models according
      to the Vermeulen's approximation and the parabolic diffusion model have been
      tested with the experimental data for adsorption of heavy metals onto natural
      zeolite. For the systems examined, the fit of the proposed models with the
      experimental data was shown to be equally good using both models. The diffusion
      coefficients are calculated from kinetic models of heavy metal ions and they are
      of the order from 10(-5) to 10(-6) cm(2)/min. The diffusion coefficients depend
      on initial concentration for both models.

PMID- 20818057
TI  - A comparative study of perchlorate degradation in acute toxicity and chronic
      toxicity.
AB  - Since the discovery of perchlorate in water system, the public has been concerned
      about its human health effect. In practice it was reported that chronic exposure
      to perchlorate may lead to damage in thyroid hormone activity. This study
      introduced a method of perchlorate reduction, using autotrophic bacteria which
      utilise hydrogen as an electron donor. Two experiments were conducted to compare
      the effects of acute and chronic perchlorate toxicity on bacterial perchlorate
      reduction potential. One was a batch-fed operation generating acute toxicity and
      another was a continuous-fed operation generating chronic toxicity. Acclimation
      period of the batch-fed operation was 14 days while that of the continuous-fed
      operation was 31 days as commensurate with double. Lots of batch tests using the
      mixed culture passing through acclimation were conducted to figure out kinetics
      of biological perchlorate reduction. The maximum perchlorate utilisation rate
      (q(max)) of the mixed culture acclimated by acute toxicity was 2.92 mg ClO(4)(
      )/mg dry-weight (DW)/d, while that of chronic toxicity was 0.27 mg ClO(4)(-)/mg
      DW/d. Half-maximum rate constants (K(s)) of acute and chronic toxicity were 567.3
      and 25.6 mg ClO(4)(-)/L respectively. This result showed that acute toxicity
      acclimated the mixed culture more rapidly and produced a higher activity for
      biological perchlorate reduction than chronic toxicity.

PMID- 20818058
TI  - Microbial indicators in natural biofilms developed in the riverbed.
AB  - Microbial indicators such as heterotrophic bacteria, total coliforms, and
      Escherichia coli in naturally developed riverbed biofilms were investigated.
      Pebbles covered with natural biofilm were sampled directly from the riverbed at
      sampling stations ranging from the upstream region within a quasi-national park
      to the midstream in the urban district. Heterotrophic bacteria densities in
      biofilm positively correlated with stream discharge. E. coli densities in biofilm
      positively correlated with temperature, which suggests the growth in the biofilm.
      It was considered that the attachment of planktonic bacteria to biofilm was
      negligible. The biofilm may serve as an internal source of false positive
      indication of fecal contamination in the water column.

PMID- 20818059
TI  - Substance flow analyses of phthalates and nonylphenols in stormwater.
AB  - The occurrence of nonylphenol and several phthalates in water environments is
      highly undesired because of their negative effects on aquatic organisms. The
      objectives of this study were to identify emission sources of phthalates,
      nonylphenol and its ethoxylates (NP/EOs) in urban stormwater, and to quantify the
      substance fluxes from the source to the stormwater system, using the methodology
      of substance flow analysis (SFA). The SFA, applied on an urban motorway area,
      showed that phthalates are mainly emitted from vehicles and coated roofing
      material, whereas the major NP/EOs sources are vehicles and concrete. It was
      estimated that approximately 4.1 kg of four selected phthalates and more than 400
      g of NP/EOs are emitted annually to stormwater in the studied area. The SFA
      approach presented in this study, using factors that express the emission rate of
      a specific substance from a specific source, could be applied in urban catchments
      of various character to estimate fluxes of water contaminants.

PMID- 20818060
TI  - Urban evaporation rates for water-permeable pavements.
AB  - In urban areas the natural water balance is disturbed. Infiltration and
      evaporation are reduced, resulting in a high surface runoff and a typical city
      climate, which can lead to floods and damages. Water-permeable pavements have a
      high infiltration rate that reduces surface runoff by increasing the groundwater
      recharge. The high water retention capacity of the street body of up to 51 l/m(2)
      and its connection via pores to the surface lead to higher evaporation rates than
      impermeable surfaces. A comparison of these two kinds of pavements shows a 16%
      increase in evaporation levels of water-permeable pavements. Furthermore, the
      evaporation from impermeable pavements is linked directly to rain events due to
      fast-drying surfaces. Water-permeable pavements show a more evenly distributed
      evaporation after a rain event. Cooling effects by evaporative heat loss can
      improve the city climate even several days after rain events. On a large scale
      use, uncomfortable weather like sultriness or dry heat can be prevented and the
      urban water balance can be attenuated towards the natural.

PMID- 20818061
TI  - Optimal rainfall temporal patterns for urban drainage design in the context of
      climate change.
AB  - The main objective of the present study is to propose a method for estimating an
      optimal temporal storm pattern for urban drainage design in southern Quebec
      (Canada) in the context of climate change. Following a systematic evaluation of
      the performance of eight popular design storm models for different typical urban
      basins, it was found that the Canadian Atmospheric Environment Service (AES)
      storm pattern and the Desbordes model (with a peak intensity duration of 30 min)
      were the most accurate for estimating runoff peak flows while the Watt model gave
      the best estimation of runoff volumes. Based on these analyses, an optimal storm
      pattern was derived for southern Quebec region. The proposed storm pattern was
      found to be the most suitable for urban drainage design in southern Quebec since
      it could provide accurate estimation of both runoff peak flow and volume.
      Finally, a spatial-temporal downscaling method, based on a combination of the
      spatial statistical downscaling SDSM technique and the temporal scaling General
      Extreme Value distribution, was used to assess the climate change impacts on the
      proposed optimal design storm pattern and the resulting runoff properties.

PMID- 20818062
TI  - Adsorption of anionic dyes in aqueous solution using chemically modified barley
      straw.
AB  - An agricultural waste derived adsorbent was prepared by chemically modified
      barley straw with NaOH and a cationic surfactant hexadecylpyridinium chloride
      monohydrate (CPC). The prepared adsorbent, BMBS, was used for removal of anionic
      dyes; Acid Blue (AB40) and Reactive Blue 4 (RB4) from aqueous solution in a batch
      adsorption system. The adsorbent was characterized by FT-IR and elemental
      composition. The stability of CPC adsorbed on straw surface was also evaluated by
      exposing to aqueous solution. In adsorption tests, influence of operation
      parameters such as contact time, initial concentration and pH of solution on AB40
      and RB4 uptake were investigated and discussed. The CPC was observed strongly
      attached to straw surface and removal percentage of AB40 and RB4 was increased
      with increasing in contact time. The adsorption of dyes on modified straw surface
      was favorable at high acidic condition and desorption was found relatively low
      upon exposing to the desorption agent (i.e water). Dynamic experiment revealed
      that the kinetic data fitted well to the pseudo-second-order model for both of
      the dyes. The isotherm study also indicated that RB4 and AB40 adsorption suited
      well with the Langmuir model, The maximum adsorption capacity determined from the
      Langmuir isotherm at 25 degrees C was 51.95 mg g(-1) and 31.5 for AB40 and RB4,
      respectively.

PMID- 20818063
TI  - Manganese waste water treatment by fungi derived from manganese slag.
AB  - The aim of this study was to isolate a mould from the surface of manganese slag
      which had strong resistance and high adsorption of Mn(2 + ), and to determine the
      effects of initial Mn(2 + ) concentration, incubation temperature, rotation speed
      and inoculation amount on adsorption of Mn(2 + ) from manganese waste water
      solution. The result showed that a mould (A5) which was isolated from manganese
      slag had the adsorption rate of Mn(2 + ) to 97.5% at the initial pH value 6,
      inoculation amount 2%, rotation speed 150 r/min, a concentration of Mn(2 + ) 500
      mg/L, and a temperature of 28 degrees C cultivated for 50 h. As there is no
      research on adsorption of Mn(2 + ) from manganese waste water by fungi before,
      this research showed a theoretical guidance on this field.

PMID- 20818064
TI  - Pathogen inactivation during passage of stormwater through a constructed reedbed
      and aquifer transfer, storage and recovery.
AB  - A study was undertaken to determine the potential inactivation rates of selected
      enteric microorganisms in captured urban stormwater within a constructed reedbed
      and in tertiary carbonated aquifer during an Aquifer Storage, Transfer and
      Recovery (ASTR) scheme. The study was undertaken in-situ in the constructed
      reedbed and aquifer using diffusion chambers. The results showed that all tested
      bacteria had one log(10) reduction time of less than 6 and 2.5 days respectively
      in constructed reedbeds and aquifer, which suggests that presence of enteric
      bacteria in the recovered water is unlikely. However, adenovirus and
      Cryptosporidium oocysts showed lower inactivation rates with one log(10)
      reduction times of more than 33 days in the constructed reedbeds. This means that
      the constructed reedbed with a mean residence time 10 days cannot be relied upon
      as an efficient treatment barrier for virus and protozoa. Storage of stormwater
      in aquifer with brackish water resulted in slow inactivation of enteric viruses
      over the 35 day incubation period with adenovirus and rotavirus showing slowest
      inactivation times (extrapolated T(90) of >100 days). Cryptosporidium oocysts
      showed similar inactivation rate in the constructed reedbed and aquifer.

PMID- 20818065
TI  - Evaluation of a bench-scale membrane fouling protocol to determine fouling
      propensities of membranes during full-scale water reuse applications.
AB  - There is increasing interest in recycling wastewater effluents for augmentation
      of existing water supplies. The treatment of wastewater effluents by an
      integrated membrane system, such as microfiltration pre-treatment followed by
      reverse osmosis, is the industry standard for groundwater recharge or reservoir
      augmentation projects. Membrane fouling, especially effluent organic matter
      fouling, is a major challenge for water reuse applications employing high
      pressure membranes. While fouling control through pre-treatment is an important
      aspect in membrane system design and operation, selecting low fouling membranes
      is an equally important aspect. Although recent research has begun to elucidate
      fouling mechanisms, little work has been performed to develop methods to pre
      determine the effluent organic matter fouling propensities of high-pressure
      membranes so that low-fouling membranes can be pre-selected for reuse
      applications. The purpose of this study was to utilize a bench-scale testing
      protocol to test the relative effluent organic matter fouling propensities of
      commercially available NF and RO membranes when treating wastewater effluents.
      Bench-scale fouling test results were then compared to operational data generated
      during pilot- and full-scale membrane testing. Pilot- and full-scale testing
      using recycled water demonstrated that membranes foul at significantly different
      rates and that the extent of fouling could be estimated utilizing the proposed
      bench-scale testing protocol.

PMID- 20818066
TI  - The hybrid process TiO(2)/PAC: performance of membrane filtration.
AB  - In investigations concerning the photocatalytic degradation by TiO(2) usually
      filter discs with a pore size of 0.22 mum and 0.45 mum are used for the removal
      of photocatalyst particles in aqueous suspensions. In this study the effective
      rejection of suspended particles by microfiltration in different types of
      membrane modules and with different membrane materials was investigated.
      Furthermore, Powdered Activated Carbon (PAC), which can be used to gain an
      increase in photocatalytic degradation rates, was investigated concerning its
      influence on the membrane performance. It is shown that by membrane filtration
      with a pore size above 0.1 mum, irrespective of the experimental conditions, no
      complete removal can be achieved. However, UV irradiation was found to improve
      the removal efficiency for all types of tested membrane materials. The addition
      of PAC also led to a higher performance of membrane filtration with regard to
      particle rejection. In long-term experiments with a hollow fibre membrane module
      in the presence of PAC a five-fold decrease of TiO(2) particles in the permeate
      could be proven. Besides, it was shown that added PAC can shield the membrane
      regarding the abrasivity of TiO(2), which could otherwise lead to the destruction
      of the membrane. Therewith PAC exhibits another crucial advantage besides its
      synergetic effect in photodegradation.

PMID- 20818067
TI  - Effect of docetaxel on expression of eIF3a in human lung cancer A549 cell line.
AB  - OBJECTIVE: To explore the dose-dependent and time-dependent effect of docetaxel
      on the expression of mammalian eukaryotic initiation factor 3 subunit A (eIF3a)
      in lung cancer cell line. METHODS: The human lung cancer cell line A549 was
      treated with gradient concentrations of docetaxel for different time. Real-time
      PCR and Western blot were used to detect mRNA and protein expression levels of
      eIF3a and alpha-tubulin, respectively. RESULTS: Docetaxel did not affect alpha
      tubulin expression at either mRNA level or protein level. When A549 cells were
      treated with high concentration of docetaxel (30 MUg/L), the expression level of
      eIF3a mRNA tended to increase in a time-dependent manner. Protein expression
      level of alpha-tubulin was not associated with eIF3a expression significantly in
      cells treated by docetaxel. CONCLUSION: Docetaxel could slightly increase the
      expression of eIF3a mRNA, and eIF3a does not regulate the expression of alpha
      tubulin in A549 cells treated by docetaxel.

PMID- 20818068
TI  - In vitro anti-tumor immune mechanism of nasopharyngeal carcinoma bispecific anti
      idiotype antibody.
AB  - OBJECTIVE: To compare the in vitro antitumor immune responses induced by bivalent
      bispecific anti-idiotype antibody G22-I50 and monovalent anti-idiotype antibody
      G22 and I50, and explore its possible mechanism. METHODS: Proteins G22-I50, G22,
      and I50 were induced and identified by Western blot and ELISA. Peripheral blood
      monoclear cells (PBMC) were isolated and stimulated with G22-I50, G22, and I50
      anti-idiotype antibodies, respectively. MTT assay and LDH release test were
      employed to examine the proliferation and cytotoxicity of the PBMC. The levels of
      IFN-gamma, IL-2, and IL-4 in the supernatant were detected by ELISA and changes
      of T lymphocyte subsets were determined by flow cytometry. RESULTS: Western blot
      showed that G22-I50, G22, and I50 had specific binding capabilities to FC2 (Ab1).
      The activities of G22-I50, G22, and I50 had recovered and these proteins could be
      used in the in vitro study. The proliferation and cytotoxicity of the PBMC
      stimulated with G22-I50 were significantly higher than those stimulated with G22
      or I50. The level of IFN-gamma and IL-2 in the culture supernatant of the PBMC
      stimulated with G22-I50 was higher than that in the G22 or I50 group, but the
      level of IL-4 did not increase. Compared with the G22 or I50 group, the
      proportion of CD4(+) and CD8(+) T cells and CD4(+)/CD8(+) ratio significantly
      increased, and the proportion of CD4(+)CD25(+) T cells significantly decreased in
      the PBMC stimulated with G22-I50. CONCLUSION: G22-I50 has more potent
      immunogenicity and would enhance specific antitumor effect which might relate to
      improving PBMC proliferation, inducing the secretion of Th1 type cytokines,
      activating CD8(+)T cells, and suppressing the expression of CD4(+)CD25(+) T
      cells.

PMID- 20818069
TI  - Proteomics of apoptosis of multiple myeloma cells induced by proteasome inhibitor
      PS-341.
AB  - OBJECTIVE: To compare the proteome difference between multiple myeloma cell line
      U266 cells treated and untreated with PS-341, to investigate the potential drug
      targets, and to provide theoretical evidence for clinical therapy of multiple
      myeloma. METHODS: Two-dimensional gel electrophoresis (2-DE) was performed to
      separate proteins from treated and untreated U266 cells with proteasome inhibitor
      PS-341. ImageMaster 2D Platinum software was used to analyze 2-DE image, and
      matrix-assisted laser desorption/ionization time of flight mass spectrometry
      (MALDI-TOF-MS) was used to identify the differentially expressed proteins. The
      expression levels of differential protein BAG-2 in the 2 groups of U266 cells
      lines were detected by Western blot. RESULTS: The 2-DE reference pattern of
      treated and untreated U266 cells with PS-341 was established. A total of 31
      differential proteins were identified by MALDI-TOF-MS, 27 of which were down
      regulated after PS-341 treatment. The differential expression level of BAG-2 in
      the 2 groups of U266 cells was confirmed by Western blot. CONCLUSION: Some down
      regulated proteins may be the potential drug targets of proteasome inhibitor PS
      341.

PMID- 20818070
TI  - Construction of luciferase reporter gene vector for human MUC5AC gene promoter
      and analysis of its transcriptional activity.
AB  - OBJECTIVE: To clone the human mucin (MUC) 5AC gene promoter and construct its
      luciferase reporter vector for human MUC5AC gene and analyze its transcriptional
      activity. METHODS: The 1 348 bp DNA sequence at the human MUC5AC gene 5 end was
      analyzed by the Vector NTI software. After the target sequence from human A549
      cells genomic DNA was amplified by PCR method, and the product of PCR was
      sequenced. By promoter deletion analysis, 3 promoter segments with different
      lengths were amplified by PCR, then the products were identified by DNA
      sequencing, and 4 promotor segments were inserted into pGL3- enhancer vectors.
      Site-specific mutagenesis technique was used to establish mutants of specificity
      protein (SP)-l and nuclear factor-kappa B (NF-kappaB) site in MUC5AC gene
      promoter. The relative luciferase activities were detected in the transfected
      A549 cells. RESULTS: Sequence analysis indicated that there were many cis-acting
      elements in the regions of 1 348 bp DNA sequence at the human MUC5AC gene 5 end.
      The 4 reporter gene vectors with promoter segments with different lengths were
      constructed successfully. Dual-luciferase assay revealed the 372 bp fragment
      including activity with the minimal fragment. Neutrophil elastase (NE) could
      increase the expression of luciferase reporter gene plasmid containing mutated NF
      kappaB version (P<0.05 vs. control) of MUC5AC promoter in the transfected A549
      cells. The induction by NE decreased markedly when the SP-l element in MUC5AC
      promoter were mutated. CONCLUSION: This research may provide an important basis
      for the further study of human MUC5AC gene promoter activity and regulation of
      gene expression. There is an up-regulative element of gene transcription in the
      region of -324 to -64 bp in MUC5AC gene upstream. SP-l site of the promotor
      mediates NE-induced MUC5AC expression in human A549 cells.

PMID- 20818071
TI  - Effect of morphine preconditioning on mitochondrial permeability transition pore
      after myocardial ischemia-reperfusion injury in rats.
AB  - OBJECTIVE: To investigate the effect of morphine preconditioning on mitochondrial
      permeability transition pore (MPTP) and its protective mechanism after myocardial
      ischemia-reperfusion injury. METHODS: A rat model of ischemia-reperfusion injury
      was established. Forty rats were injected with 2-(3)[H] DOG and then divided into
      4 groups randomly: a sham operation (S) group, an ischemia-reperfusion injury
      (IR) group, a morphine preconditioning (Mp+IR) group, and a cyclosporine A
      preconditioning (CsA+IR) group. We monitored the concentrations of serum creatine
      kinase-Mb (CK-Mb) and cardiac troponin I (cTnI), and measured myocardial
      mitochondrial 2-(3)[H] DOG, cytochrome c content, Ca(2+) concentration
      ([Ca(2+)]m), the velocity of Ca(2+) intake and reaction half time of
      mitochondrial permeability transition pore (MPTP t(1/2)) in the 4 groups.
      RESULTS: The concentrations of serum CK-Mb and cTnI decreased more in the Mp+IR
      group and the CsA+IR group than those of the IR group. The concentrations of 2
      (3)[H]DOG and [Ca(2+)]m in the IR group were evidently higher but the level of
      cytochrome c was lower than those of the sham operation group. The concentrations
      of 2-(3)[H] DOG and [Ca(2+)]m in the Mp+IR group decreased whereas the
      concentration of cytochrome c increased compared with those in the IR group.
      Mitochondrial 2-(3)[H]DOG content was positively correlated with the
      concentration of calcium (r=0.797, P<0.01). The 2-(3)[H]DOG and [Ca(2+)]m content
      were negatively correlated with cytochrome c in the IR group (r=-0.805 and r=
      0.648, respectively, P<0.01). MPTP t(1/2) in the IR group was shortened
      evidently, and that in the Mp+IR and CsA+IR group was significantly lengthened.
      CONCLUSION: Morphine preconditioning may have myocardial protective effect
      through unburdening the calcium overload and lengthening the MPTP t(1/2).

PMID- 20818072
TI  - Losartan attenuates vascular remodeling of the aorta in spontaneously
      hypertensive rats and the underlying mechanism.
AB  - OBJECTIVE: To determine the effect of losartan on vascular remodeling and the
      underlying mechanism in spontaneously hypertensive rats(SHR). METHODS: SHR of 12
      weeks old were given losartan orally [0, 15, 30 mg/(kg.d), n=12]. The tail
      arterial pressure was measured every week. Eight weeks later, the pathological
      changes and p22(phox) expression in the thoracic aorta, the activity of catalase
      (CAT), the contents of H(2)O(2) and Ang II in the plasma were evaluated. RESULTS:
      Blood pressure was increased in the SHR accompanied by the thickened wall and
      increased p22(phox) expression in the thoracic aorta. The plasma levels of
      H(2)O(2) and Ang II were elevated while the CAT level was decreased in the SHR.
      Administration of losartan reversed the thickened wall and increased the CAT
      activity concomitantly with the decreased plasma levels of H(2)O(2) and p22(phox)
      expression in the SHR. The plasma level of Ang II increased after the losartan
      treatment. CONCLUSION: Oxidative stress induces the vascular remodeling of the
      aorta in the SHR. Losartan can reverse the vascular remodeling through down
      regulating p22(phox) expression and inhibiting the oxidative stress.

PMID- 20818073
TI  - Improved conjunctival transplantation for corneal ulcer.
AB  - OBJECTIVE: To evaluate the therapeutic effect of pedical conjunctival flap
      transposition on refractory corneal ulcer. METHODS: The data of 56 eyes of 56
      patients with refractory corneal ulcer who underwent pedical conjuctival
      transposition in a tertiary eye unit in China from June 2005 to June 2009 were
      retrospectively analyzed. There were 36 infective corneal ulcers, 9 keratoplasty
      graft ulcers, 4 traumatic ulcers, and 7 chemical burn ulcers. All patients were
      treated with focal debridement and pedical conjuctival flap transposition.
      RESULTS: Forty-seven out of 56 (83.9%) were cured after one surgery, and 5 (8.9%)
      had conjunctival flap retraction, among which 3 underwent the second surgery and
      2 had the third surgery to completely heal. Four patients (7.2%) turned to
      lamellar keratoplasty because of fungal corneal ulcer relapse. Ulcer in 52
      patients healed and the globe preserved. They had different levels of vision
      improvement. CONCLUSION: Pedical conjunctival flap transposition is effective for
      refractory corneal ulcer.

PMID- 20818074
TI  - [Sequencing of mitochondrial DNA cytochrome oxidase subunit I gene in
      sarcosaphagous flies from 14 provinces in China].
AB  - OBJECTIVE: To detect the 278 bp region of gene of the cytochrome oxidase subunit
      I (COI) in mitochondral DNA (mtDNA) of sarcosaphagous flies, identify the species
      of sarcosaphagous flies, and provide reference for forensic application. METHODS:
      Samples were collected in Baotou and Chifeng of Inner Mongolia, Tianjin, Nanning,
      Fuzhou, Linyi of Shandong, Shijiazhuang, Yinchuan, Lanzhou, Huairou of Beijing,
      Xinxiang and Nanyang of Henan, Datong of Shanxi, Wuhu of Anhui, Quzhou of
      Zhejiang, Changsha, Zhuzhou and Yongzhou of Hunan. A total of 38 flies were
      randomly collected from rabbits, dogs and pigs which were set outdoors, then the
      flies' mitochondrial DNA (mtDNA) were extracted by the improved small insects DNA
      homogenate method. Amplification was conducted by Perkin-Elmer 9600 thermal
      cycler, then vertical non-denaturing 7% polyacrylamide gelectrophoresis. PCR
      products were purified using the nucleic acid purification kit. Sequences of both
      strands were obtained by direct sequence of the double-stranded PCR product using
      one of the PCR primers and the ABI PRISM big dye terminator cycle sequencing dit.
      Sequence reactions were electrophorsed on ABI Model 3730 DNA Sequencers. A UPGMA
      tree was contrasted using the maximum composite likelihood method in MEGA4.
      RESULTS: The 38 sarcosaphagous flies belonged to 3 families(Muscidae,
      Calliphoridae, and Sarcophagidae), 10 genuses (Musca Linnaeus, Hydrotaea Robineau
      Desvoidy, Aldrichina Townsend, Hemipyrellia Townsend, Achoetandrus Bezzi,
      Protophormia Townsend, Chrysomya Robineau-Desvoidy, Lucilia Robineau-Desvoidy,
      Helicophagella Enderlein, and Boettcherisca Rohdendorf), and 12 species [Musca
      domestica (Linnaeus), Hydrotaea (Ophyra) capensis (Wiedemann), Lucilia caesar
      (Linnaeus), Lucilia illustris (Meigen), Aldrichina graham (Aldrich), Hemipyrellia
      ligurriens, Achoetandrus (Chrysomya) rufifacies (Macquary), Protophormia
      terraenovae (Robineau-Desvoidy), Chrysomya megacephala (Fabricius), Lucilia
      sericata (Meigen), Helicophagella melanura (Meigen), and Boettcherisca peregrine
      (Robineau-Desvoidy)]. CONCLUSION: The genus of the sarcosaphagous flies can be
      identified by 278 bp gene sequence analysis of CO I in mtDNA. This method is
      rapid, convenient and precise.

PMID- 20818075
TI  - [Genetic polymorphism in tyrosine hydroxylase gene and essential hypertension in
      Hunan Han population].
AB  - OBJECTIVE: To investigate the association of tyrosine hydroxylase (TH) C-824T
      polymorphism with essential hypertension (EH) susceptibility in Hunan Han
      population by a case-control study. METHODS: A case-control study was performed
      on 368 EH patients and 353 healthy controls of Han nationality recruited in Hunan
      province. Polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP)was used to genotype the C-824T polymorphism. RESULTS: (1) Genotype
      frequencies for TH-824CC and -824CT+-824TT genotypes were 89.9% and 10.1%,
      respectively for EH patients and 88.7% and 11.3%, respectively for the controls.
      No significant difference in the genotype distribution of C-824T polymorphism
      between the patients and controls was observed (P=0.579). Allele frequencies of
      TH C-824T also showed no significant difference between the patients and controls
      (P=0.515). (2) When adjusted by EH risk factors, results of unconditional
      logistic regression analysis showed that there was no association between TH C
      824T polymorphism and EH susceptibility (P=0.264). (3) When stratified by gender,
      no significant difference in the genotype distribution of TH C-824T polymorphism
      was observed between the patients and controls in either male or female subjects
      (P=0.841 and P=0.288). (4) Diastolic blood pressure (DBP) in individuals with 
      824 CT+TT genotype was significantly higher than that in individuals with -824 CC
      genotype in the controls (P=0.015). (5) When stratified by gender, significant
      difference in DBP between TH C-824T CT+TT genotype and CC genotype was observed
      in the male (P= 0.018) but not in the female (P=0.083) controls. CONCLUSION:
      There is no association between TH gene C-824T polymorphism and EH susceptibility
      in Hunan Han population. The TH gene C-824T polymorphism is possibly associated
      with increased DBP in the males in Hunan Han population.

PMID- 20818076
TI  - [Change of p-CREB after surgical incisional pain in rat spinal cord].
AB  - OBJECTIVE: To explore the role of phosphorylation of cAMP response element
      binding protein (CREB) in the incision-induced pain hypersensitivity. METHODS: A
      longitudinal incision was made in one plantar hind paw of isoflurane-anesthetized
      rats. Spinal cords were removed at various postoperative time after behavior
      test. Phosphorylation of CREB was determined by immunohistochemistry and double
      labeling immunofluorescence. Morphine and gabapentin were intraperitoneally
      injected before the behavior test and were used to determine the interaction
      between phosphorylation of CREB and morphine and gabapentin. RESULTS: After the
      hind-paw incision, phosphorylation of CREB was enhanced in the ipsilateral lumbar
      spinal cord (P<0.05). The enhancement of p-CREB was mainly in the neurons in the
      dorsal horn of the spinal cord. All these were shown by double-labeling technique
      and p-CREB was mainly in the neurons. Intraperitoneal injection of morphine
      prevented the increased phosphorylation of CREB in the spinal cord and inhibited
      the mechanical allodynia induced by the incision (P>0.05). Gabapentin didn't
      inhibit the phosphorylation of CREB (P<0.05) but partly inhibited the mechanical
      allodynia. CONCLUSION: Incision induces the phosphorylation of CREB in the spinal
      cord, and the increase of p-CREB is mainly in the neurons. Phosphorylation of
      CREB in the spinal cord contributes to the pain hypersensitivity induced by
      surgical incision.

PMID- 20818077
TI  - [Effect of tanshinone IIA on the change of calcium current induced by beta
      amyloid protein 25-35 in neurons of nucleus basalis of Meynert].
AB  - OBJECTIVE: To explore the effect of tanshinone IIA (TanIIA) on calcium current
      induced by beta-amyloid protein 25-35 (Abeta25-35) in neurons of nucleus basalis
      of Meynert (nbM). METHODS: Cell acute dissociated technique and the whole-cell
      recording model of patch-clamp technique of single-cell were used. The voltage
      dependent calcium current in neurons of nbM was recorded in SD rats first. Then
      the effect of TanIIA on the voltage-dependent calcium current in the neurons was
      assayed. The change of calcium current induced by Abeta25-35 as well as the
      effect of TanIIA on the change of calcium current induced by Abeta25-35 in
      neurons of nbM were analyzed. RESULTS: Extracellular fluid containing different
      concentrations of TanIIA was irrigated, respectively. The peak current did not
      change obviously. There was no difference in current density between the TanIIA
      group and the control group at 0 mV (P>0.05). Extracellular fluid containing 200
      nmol/L Abeta25-35 was irrigated after the normal calcium current recorded under
      whole patch clamp, and the peak current changed obviously. There was distinct
      difference in the current density between the Abeta group and the control group
      at 0 mV (P<0.05). Extracellular fluid containing Abeta25-35 and different
      concentrations of TanIIA were irrigated after the normal calcium current was
      recorded under whole patch clamp, respectively, and the peak current did not
      change. There was no difference in current density between the TanIIA +Abeta
      group and the control group at 0 mV (P>0.05). CONCLUSION: In vitro, TanIIA could
      inhibit the calcium current amplification induced by Abeta25-35 in neurons of
      nbM. TanIIA may protect neurons against the toxicity of Abeta and decrease the
      inward flow of Ca(2+).

PMID- 20818078
TI  - [Prokaryotic expression and antigenicity of the CagA gene in Helicobacter
      pylori].
AB  - OBJECTIVE: To synthesize the specific CagA gene segment of the gastric cancer
      idiotype Helicobacter pylori (H. pylori), establish the prokaryotic expression
      system and identify the antigenicity sequence of recombination signals. METHODS:
      We selected the CagA fragment which was related to gastric cancer in our earlier
      research. The CagA gene segment was optimized and synthesized. The synthesized
      CagA gene was cut from the pUC57-CagA plasmid and then was carried by expression
      vector pET32a to be transformed into the host bacterium BL21 (DE3). The
      positively cloned pET32a-CagA was selected by receptivity of aniline and colony
      PCR. The host bacterium with pET32a-CagA was induced by IPTG to express fusion
      protein. The expression of CagA protein was analyzed by SDS-PAGE gel
      electrophoresis and the antigenicity of fusion protein was examined by Western
      blot. RESULTS: CagA gene segment was designed and synthesized. The sequence of
      synthesis CagA gene segment was the same as the one designed before (AF289435).
      We successfully constructed the plasmid of prokaryotic expression of the pET32a
      CagA. Homology of the target CagA proteinum was 100%, the same as AAG09884. The
      host bacterium BL21 (DE3) containing pET32a-CagA could express CagA fusion
      protein after the IPTG induction. SDS-PAGE gel electrophoresis showed that the
      molecular weight of fusion protein was the same as expected (45 kD). Western blot
      showed that the fusion protein could be combined with the antibody of the whole
      bacterium of anti-H. pylori. CONCLUSION: The synthesized CagA fusion protein from
      the prokaryotic expression system has antigenicity. We hope to set the foundation
      for selecting the strain in H. pylori correlated to gastric cancer and
      corresponding therapy in clinical practice.

PMID- 20818079
TI  - [Differential proteomic analysis of drug resistant A549/DDP cell lines in human
      lung adenocarcinoma].
AB  - OBJECTIVE: To establish 2-dimensional electrophoresis (2-DE) graph of A549 and
      A549/DDP cell lines, to identify the differentially expressed proteins, and to
      screen multidrug resistance (MDR) related proteins in human lung adenocarcinoma.
      METHODS: The total proteins of A549 and A549/DDP cells were obtained, and were
      extracted and separated by 2-DE. PDQuest software was applied to analyze the 2-DE
      images, and the differential proteins of the 2 types of cells were identified by
      matrix-assisted laser desorption/ionization time of flight mass spectrometry
      (MALDI-TOF-MS). Western blot was used to determine the expression levels of the 4
      proteins. RESULTS: We established 2-DE maps of total proteins from A549 and
      A549/DDP. A total of 40 differential protein spots in the 2 cell lines were
      found, and 23 differential expression proteins were identified by MALDI-TOF-MS.
      Western blot showed that heat shock protein beta-1, annexin A4, cofilin l,
      vimentin were differential expression proteins in A549 and A549/DDP, which was
      consistent with the results of the comparative proteomic analysis. CONCLUSION:
      The 23 differential expression proteins in human lung adenocarcinoma are useful
      for studying the MDR mechanism of lung adenocarcinoma.

PMID- 20818080
TI  - [Flow imaging of residual neck lymph nodes in nasopharyngeal carcinoma by
      contrast-enhanced ultrasonography after radiotherapy].
AB  - OBJECTIVE: To explore the value of flow imaging with contrast-enhanced ultrasound
      for residual neck lymph nodes in nasopharyngeal carcinoma after radiotherapy.
      METHODS: Blood flow imaging of 50 residual cervical lymph nodes in 36 patients
      with nasopharyngeal carcinoma after radiotherapy was observed and compared by
      color doppler ultrasound and contrast-enhanced ultrasonography. RESULTS: In the
      50 remaining lymph nodes in the neck, 40 blood flow signals were increased, 10
      did not significant change by contrast-enhanced ultrasonography. The blood flow
      in residual lymph nodes by contrast-enhanced ultrasonography was richer than that
      by color doppler ultrasound. There was a significant difference in the blood flow
      signals between contrast-enhanced ultrasonography and color doppler ultrasound
      (chi(2)=49.172, P<0.01). CONCLUSION: Contrast-enhanced ultrasonography can help
      blood flow imaging of the residual lymph nodes in nasopharyngeal carcinoma after
      radiotherapy, which may provide the imaging basis for clinical diagnosis and
      treatment.

PMID- 20818081
TI  - [Effect of Velcade combined with Dexamethasone on multiple myeloma].
AB  - OBJECTIVE: To compare the effect and safety between Velcade-Dexamethasone (VD)and
      revised Vinorebine+Pirarubicin+ Dexamethasone (VAD) regiment for multiple myeloma
      (MM). METHODS: Thirty-six patients with MM were reviewed, 16 of whom were treated
      with VD (VD Group) and the others with VAD. European Group for Blood and Marrow
      Transplant (EBMT) criteria and National Cancer Institute Common Terminology
      Criteria for Adverse Events (NCICTCAE) were chosen to analyze the efficacy and
      side effects. RESULTS: In the VD group and the revised VAD group, the rates of
      complete response, partial response, minimal response, no change and progress
      disease were 50% vs. 5%, 25% vs. 25%, 18.8% vs. 15%, 6.2% vs. 35% and 0 vs. 20%,
      respectively. The total response rates were 93.8% vs 45%. There was significant
      difference in the overall response rate between the 2 groups (P<0.05). The side
      effects were less serious, and the endurance was better in the VD group than
      those in the revised VAD group. No serious effects of hematology and cardiology
      were seen, and good endurance was showed in the renal dysfunction in the VD
      group. CONCLUSION: Velcade combined with dexamethasone is a safe and effective
      regiment for multiple myeloma with good safety and endurance.

PMID- 20818082
TI  - [Effect of GM6001 on the model that cervical squamous carcinoma cell line HCE1
      multicellular spheroids invade live human umbilical vein endothelium cell
      monolayers].
AB  - OBJECTIVE: To investigate the relationship between matrix matrix
      metalloproteinases (MMP)-9 expression in HCE1/multicellular spheroids (MCS) and
      invasion of cervical carcinoma, and to explore the effect of MMPs inhibitor
      GM6001 on the model that HCE1/MCS invade live human umbilical vein endothelium
      cell (HUVEC). METHODS: We established the invasion model by coculturing HCE1/MCS
      and HUVEC, and detected the MMP-9 expression in HCE1 monolayer cells (HCE1/MC),
      HCE1/MCS and HUVEC using immunohistochemistry and treated the HCE1/MCS invasion
      model with GM6001. RESULTS: A cervical squamous carcinoma cell HCE1 infiltrating
      model was established. Compared with that in HCE1/MC, MMP-9 expression in the
      HCE1/MCS was significantly higher (P<0.05). Compared with the control group, the
      invasion of HCE1/MCS was inhibited by 26.09% and 92.95% (P<0.05) in the GM6001
      2.5 MUmol/L and 12.5 MUmol/L group. MMP-9 expression in HCE1/MCS in the GM6001
      12.5 MUmol/L group was obviously lower than that in the control group (P<0.05).
      With the increase of the concentration of GM6001, the inhibition increased.
      CONCLUSION: The enhancement of HCE1/MCS invasion may be related to the up
      regulation of MMP-9 expression in HCE1/MCS. GM6001 can down regulate the MMP-9
      expression in HCE1/MCS and partially block the HCE1/MCS invasion to HUVEC.

PMID- 20818083
TI  - [Clinical features and prognosis of cervical cancer in young women].
AB  - OBJECTIVE: To investigate the prevalence, etiology, clinical presentation and
      pathological features, treatment and prognosis of cervical cancer in young women.
      METHODS: Clinical data of 132 young women with cervical cancer were reviewed.
      RESULTS: Positive rate of human papillomavirus 18 was high in young women with
      cervical cancer. The primary clinical presentation of young patients with
      cervical cancer was contact bleeding of vagina, and the signs were out-expanding
      of cervical mass. The percentage of adenocarcinoma increased. The main treatment
      for cervical cancer was surgery. The patients had radical hysterectomy plus
      ovarian transplantation, none of whom had ovarian metastases and menopause
      syndrome. Prognosis of most patients was good. CONCLUSION: Contact bleeding is a
      significant symptom in young women with cervical cancer. Surgery is first
      considered in the treatment. Preoperative neoadjuvant chemotherapy can be used in
      patients with locally advanced and late stage cervical cancer. Ovarian
      transplantation during operation can retain the ovary function.

PMID- 20818084
TI  - [Copy number and deletion of 4 977 bp of granular cell mitochondria DNA in
      patients with diminished ovarian reserve].
AB  - OBJECTIVE: To determine the copy number of granular cell mitochondria DNA (mtDNA)
      and deletion of 4 977 bp in patients with diminished ovarian reserve (DOR) to
      primarily study the structural integrity of granular cell mtDNA. METHODS: We
      selected 50 DOR patients and 50 patients with normal ovarian reserve (NOR).
      Granular cells in liquor folliculi of these patients were collected at ovum pick
      up day. DNA was extracted from the granular cells. The mtDNA 4 977 bp deletion of
      granular cells was detected by PCR and the number of granular cells mtDNA copies
      was detected by real-time PCR. RESULTS: No 4 977 bp deletion of ovary granular
      cell mitochondria DNA in the 100 patients was detected. There was no significant
      difference in the relative quantity of granular cell mitochondria DNA in the DOR
      group and the NOR group. CONCLUSION: The structure of granular cells mtDNA in DOR
      patients is complete and granular cells may be used as donor cells for DOR
      patients plasma autologous transplants mitochondorial.

PMID- 20818085
TI  - [Cardioprotection of adenosine treatment in cadaver donor rats with warm
      ischemia].
AB  - OBJECTIVE: To determine the cardioprotection of adenosine treatment in cadaver
      donor rats with warm ischemia. METHODS: Rats were randomly divided into 7 groups.
      Group C was a control group. Group I(5), I(15), and I(30): The donor hearts from
      the cadaver rats that died of acute hemorrhagic shock and within warm ischemic
      durations of 5, 15, and 30 min, respectively, and the donor hearts were perfused
      with STH-1 for 30 min before cervical heterotopic heart transplantation. Group
      A(5), A(15), and A(30) were adenosine treatment groups and the donor hearts were
      obtained as mentioned above and perfused with STH-1 plus adenosine (adenosine
      concentration 1.2 mmol/L) before cervical heterotopic heart transplantation. We
      detected the change of the grafts including ultrastructure, the level of ATP,
      SOD, and MDA, NF-kappaB mRNA, TNF-alpha, and IL-6 24 h after the transplantation.
      RESULTS: At the same time point, compared with Group I(5), I(15), and I(30),
      Group A(5), A(15), and A(30) showed increased ATP and SOD in the myocardial
      tissues, and decreased MDA, NF-kappaB mRNA, TNF-alpha, and IL-6 (P<0.05).
      CONCLUSION: Adenosine treatment can protect the graft in cadaver donor rats with
      warm ischemia. The mechanism may improve the myocardial energy metabolism,
      attenuate lipid peroxidation injury, suppress the expression of NF-kappaB mRNA,
      and decrease the inflammatory damage of TNF-alpha and IL-6.

PMID- 20818086
TI  - [Treating superficial hemangioma in children according to local blood flow].
AB  - OBJECTIVE: To treat superficial hemangioma in children according to the local
      blood flow. METHODS: A total of 98 children with superficial hemangiomas admitted
      to our hospital from January 2005 to June 2009, and their clinical data were
      analyzed. RESULTS: According to the local blood flow velocity, 98 children were
      treated with injections or injection plus surgical treatment, respectively.
      Ninety-four children (95.9%) were cured. CONCLUSION: Injection therapy is
      effective for children with superficial hemangioma, but we should arrange
      individualized treatment according to the local blood flow in children.

PMID- 20818087
TI  - [Activin and activin receptors in related gynecologic and obstetric diseases].
AB  - Activin is a member of the transforming growth factor-beta (TGF-beta) superfamily
      that result from the assembly of disulphide-linked betaA and betaB subunits.
      Activin receptors are transmembrane proteins and activin fulfils the biological
      function through the signal transduction of the receptor system. In recent years,
      many studies have suggested that activins have wide biological activities. It is
      the basic medium in regulating histiocytic function and plays a role in
      maintaining the normal function of cells. Moreover, abnormal expression of
      activin in the tissues of many gynecologic and obstetric diseases, such as
      epithelial ovarian tumor, endometrial carcinoma, pre-eclampsia, polycystic ovary
      syndrome, endometriosis and so on affects the development of these diseases.

PMID- 20818088
TI  - Influenza preparedness in low-resource settings: a look at oxygen delivery in 12
      African countries.
AB  - BACKGROUND: Pandemic influenza poses a serious threat to populations in low and
      lower-middle income countries that face delays in access to health care and
      inadequately equipped facilities. Oxygen is first-line therapy for influenza
      related hypoxia and a standard component of emergency respiratory resuscitation,
      yet remains a scarce resource in many countries. METHODOLOGY: A snapshot survey
      of oxygen supply and associated infrastructure was performed at 231 health
      centres and hospitals in twelve African countries using the World Health
      Organization (WHO) Tool for Situational Analysis to Assess Emergency and
      Essential Surgical Care. WHO Global Initiative for Emergency and Essential
      Surgical Care, WHO regional and country offices, and local Ministries of Health
      facilitated data collection from facilities surveyed. Data was stored in the WHO
      DataCol SQL database and computerized spreadsheet tools were used to generate
      descriptive statistics. RESULTS: Ninety-nine (43.8%) of facilities surveyed
      reported uninterrupted access to an oxygen source and 55 (24.6%) possessed a
      fully functioning oxygen concentrator. Electricity was fully available at only 81
      (35.1%) health facilities. CONCLUSIONS: In addition to efforts to secure vaccines
      and antivirals, future global influenza preparedness efforts should include
      investments in oxygen and associated equipment and infrastructure at first
      referral health facilities, to minimize morbidity and mortality from influenza in
      regions with limited medical resources. Increasing oxygen delivery capacity in
      these areas may also provide long-term, post-pandemic benefits in the management
      of other medical conditions of significance, including trauma, neonatal pulmonary
      hypofunction, and HIV-related and childhood pneumonia.

PMID- 20818089
TI  - Helminthic infections mimicking malignancy: a review of published case reports.
AB  - BACKGROUND: Infectious diseases, including infections with helminths, can
      initially present similarly to malignancies. The goal of the article is to review
      reports of helminthic infections that are initially diagnosed as malignancy.
      METHODOLOGY: The database PubMed was searched for English language references
      published as of July 2009. RESULTS: The following published case reports and case
      series, mainly from Asia and Africa, were identified: Nematodes: 8 publications
      (1 patient with Angiostrongylus cantonensis, 2 Stronglyloides stercoralis, 1
      Toxocara species, 1 Dioctophyma renale, 1 Ascaris species, 1 Gnathostoma
      spinigerum, 1 Dirofilaria repens); Trematodes: 7 publications (46 patients with
      Schistosoma species, 2 Fasciola hepatica, 1 Paragonimus westermani); Cestodes: 6
      publications (10 patients with Echinococcus species, 1 Sparganum mansoni).
      CONCLUSION: To avoid unnecessary investigations and treatment, physicians should
      be aware when diagnosing patients from Asia or Africa that a large number of
      helminthic infections can present similar to malignancies.

PMID- 20818090
TI  - Clinical characteristics and outcomes of bacteraemic melioidosis in a teaching
      hospital in a northeastern state of Malaysia: a five-year review.
AB  - BACKGROUND: Melioidosis is an important public health problem causing community
      acquired sepsis in the northeastern part of Malaysia. METHODOLOGY: From January
      2001 to December 2005, we reviewed case reports of all bacteraemic melioidosis
      admitted to a tertiary teaching hospital, Hospital Universiti Sains Malaysia.
      RESULTS: Thirty-five patients had positive blood culture for meliodosis and 27
      case reports were traceable for further analysis. The mean age was 46.8 + 20.0
      years. Twenty patients (74.1%) were male. The main clinical presentation was
      fever that occurred in 23 (85.2%) patients. Eighteen patients (66.7%) had lung
      involvement and three patients had liver abscess. Two patients presented with
      scrotal swelling, one of whom further developed Fournier's Gangrene. Nineteen
      (70.4%) patients had underlying diabetes, five of whom were newly diagnosed
      during the admission. Thirteen (48.1%) patients were treated with high-dose
      ceftazidime and six (22.2%) patients were treated with imipenem. Eight (29.6%)
      patients were not given anti-melioidosis therapy because the causative agents
      were not identified until after the patients died. The patients were admitted
      16.8 days + 18.1. Seventeen patients (63.0%) died in this series, 13 patients of
      whom died within four days of admission. CONCLUSIONS: The wide range of clinical
      presentations and the fatal outcomes of melioidosis require a high level of
      suspicion among physicians to develop an early appropriate therapy and reduce the
      mortality rate.

PMID- 20818091
TI  - Bacterial contamination of stethoscopes used by health workers: public health
      implications.
AB  - BACKGROUND: This study was designed to assess both the potential for bacterial
      transmission by stethoscopes used by health-care workers in Nigeria and the
      implications for patient safety and control of hospital-acquired infections.
      METHODOLOGY: A structured questionnaire was administered to health workers and
      the surface of the diaphragm of their stethoscopes swabbed for bacteriological
      analysis using standard techniques. RESULTS AND CONCLUSIONS: Of the 107
      stethoscopes surveyed, 84 (79%) were contaminated with bacteria; 59 (81%) of the
      contaminated stethoscopes belonged to physicians and 25 (74%) were from other
      health workers. Isolates included Staphylococcus aureus (54%), Pseudomonas
      aeruginosa (19%), Enterococcus faecalis (14%), and Escherichia coli (13%). All
      stethoscopes that had never been cleaned were contaminated while lower levels of
      contamination were found on those cleaned one week or less before the survey
      (chi(2) = 22.4, P < .05). Contamination was significantly higher on stethoscopes
      cleaned with only water (100%) compared to those cleaned with alcohol (49%)
      (chi(2) = 30.17, P < .05). Significantly fewer (9%) stethoscopes from health
      workers who washed their hands after seeing each patient were contaminated when
      compared with the instruments (86%) of those who did not practice hand washing
      (chi(2) = 23.79, P < .05). E. coli showed the highest antibiotic resistance,
      while S. aureus showed the highest antibiotic susceptibility. Strict adherence to
      stethoscope disinfection practices by health workers can minimize cross
      contamination and ensure improved patient safety in hospital environments.

PMID- 20818092
TI  - HCV and HIV prevalences strongly correlated in Asian communities with reservoirs
      of HIV in high-risk groups.
AB  - BACKGROUND: In some Asian communities, HIV epidemics initially concentrated in
      high-risk groups develop into generalized epidemics, while in others HIV
      epidemics remain confined to high-risk groups. We examined whether blood
      exposures in a community, as indicated by hepatitis C virus (HCV) prevalence, can
      account for the variability in HIV prevalence in Asia. METHODOLOGY: We searched
      the published literature for temporally comparable HCV and HIV prevalence
      estimates for pregnant women and other "low-risk" population segments in Asian
      communities with established HIV epidemics in injection drug users or prostitute
      women. We assessed the correlation between HCV and HIV prevalences in these
      communities. RESULTS: HCV and HIV prevalences were strongly correlated (r = .97,
      p < .001). CONCLUSION: This finding suggests that blood-borne transmission drives
      generalized HIV epidemics in Asia and highlights the need for appropriately
      designed investigations of transmission modes.

PMID- 20818093
TI  - Effects of malaria in pregnancy on newborn anthropometry.
AB  - BACKGROUND: Malaria in pregnancy remains a major cause of infant mortality
      through its contribution to preterm delivery, low birth weight and intrauterine
      death. METHODOLOGY: During a cross-sectional study of 983 mothers delivering in a
      secondary health care facility in Ibadan, southwestern Nigeria, an area of high
      malaria transmission, the effect of maternal and placental malaria parasitaemia
      on newborn anthropometry was evaluated. Malaria parasitemia was detected by
      microscopy of Giemsa stained thick blood smears. RESULTS: Placental, maternal and
      combined placental and maternal malaria parasitaemia rates at the time of
      delivery were 13.1%, 12.7% and 11.1% respectively. The geometric mean parasite
      densities in maternal and placental smears were significantly higher in
      primigravid mothers than others (p = 0.004 and 0.002 respectively). Low birth
      weight rate was higher among babies born to mothers with maternal parasitaemia
      compared to those without (8.0 % versus 6.3%, p < 0.05). The mean birth weight
      was lower in neonates of mothers with peripheral and placental parasitaemia by
      138 g and 122 g (p = 0.01 and 0.02) respectively, while the respective difference
      was up to 168 g and 151 g among primigravidae (p = 0.03 and 0.04). Neonates of
      mothers with maternal and placental parasitaemia had a lower mean length than
      those without parasitaemia (48.2 vs 49.2cm, p = < 0.0001 and 48.5 vs 49.2cm p =
      0.02 respectively). Occiptofrontal circumference and ponderal indices were not
      significantly affected by maternal malaria parasitaemia. CONCLUSION: Malaria in
      pregnancy results in symmetric foetal growth restriction and the effect is more
      marked among primigravid mothers.

PMID- 20818094
TI  - Prevalence of microorganisms of hygienic interest in an organized abattoir in
      Mumbai, India.
AB  - BACKGROUND: The magnitude of food-borne illnesses in India is unknown because of
      lack of surveillance networks. Monitoring the prevalence of food-borne pathogens
      and indicators of contamination in primary production at abattoirs is imperative
      for creating a data bank and for effective control of such pathogens before they
      enter the food chain. METHODOLOGY: Microorganisms of hygienic interest were
      screened for their prevalence at Deonar Abattoir, Mumbai. Swab samples from 96
      sheep/goat carcass sites were collected and analyzed for Staphylococcus spp.,
      Bacillaceae, Clostridiaceae and Enterobacteriaceae. RESULTS: Average
      Staphylococcus aureus and Staphylococcus epidermidis counts were 3.15 +/- 0.18
      and 3.46 +/- 0.17 log10 CFU/cm(2), respectively. Bacillus cereus, Bacillus
      subtilis and Clostridium spp. counts were 3.10 +/- 0.08, 3.41 +/- 0.19 and 0.76
      +/- 0.06 log10 CFU/cm(2), respectively. The Escherichia coli count was 3.54 +/-
      0.06 and the Klebsiella aerogenes count was 3.22 +/- 0.22 log10 CFU/cm(2). Counts
      for Proteus vulgaris and Proteus mirabilis were 3.44 +/- 0.14 log10 CFU/cm(2) and
      3.71 +/- 0.12 log10 CFU/cm(2), respectively. S. epidermidis had the highest
      percentage prevalence at (41.6%), followed by K. aerogenes (31.9%), B. subtilis
      (28.2%) and P. vulgaris (23.6%). Salmonella spp. were not isolated. CONCLUSIONS:
      The data demonstrate high prevalence and diversity of micro flora on carcasses in
      the primary Indian production facility, which might be attributed to either human
      handling or improper dressing especially during evisceration process. Appropriate
      training for personal and production hygiene is essential for workers in Indian
      meat production facilities.

PMID- 20818095
TI  - Crimean-Congo hemorrhagic fever in a dengue-endemic region: lessons for the
      future.
AB  - Crimean-Congo hemorrhagic fever and dengue hemorrhagic fever are endemic in
      Pakistan. However, the overlap of geographic distribution and early clinical
      features between the two conditions make a reliable diagnosis difficult in the
      initial stage of illness. A 16-year-old boy presented with a history of
      hematemesis and high-grade fever. A preliminary diagnosis of dengue hemorrhagic
      fever was made and supportive treatment was instituted; however, the patient
      continued to deteriorate clinically. Dengue IgM antibody testing was negative on
      the third day of admission. Qualitative polymerase chain reaction test for
      Crimean-Congo hemorrhagic fever viral RNA was sent but the patient expired
      shortly after the results became available on the sixth day of admission.
      Considerable resources had to be expended on contact tracing and administration
      of ribavirin prophylaxis to all the health-care workers who had come in contact
      with the patient. It is crucial that Crimean-Congo hemorrhagic fever be
      recognized and treated at an early stage because of longer term financial and
      health implications for contacts such as health-care workers in the setting of a
      developing country. Increased surveillance of dengue and Crimean-Congo
      hemorrhagic fever cases is warranted for the derivation of reasonably reliable,
      cost-effective and prompt predictors of disease diagnosis. These predictors can
      help guide future decisions in the management of similar cases. Ultimately, such
      a strategy may translate into better cost containment in resource-poor settings.
      Institution of ribavirin prophylaxis in selected patients also merits
      consideration.

PMID- 20818096
TI  - Acute acalculus cholecystitis and hepatitis caused by Brucella melitensis.
AB  - Acute cholecystitis is a very rare presentation of brucellosis. A case of
      acalculous cholecystitis caused by Brucella melitensis is reported with a review
      of previously reported cases.

PMID- 20818097
TI  - Mortality from Influenza A/H1N1 in a tertiary care teaching institution in North
      India.
AB  - BACKGROUND: The recent influenza A/H1N1 pandemic has caused considerable
      morbidity and some mortality and is therefore a severe threat to certain
      individuals. Up to 31 January 2010, there had been 1,229 confirmed deaths from
      Influenza A/H1N1 in India. METHODOLOGY: This study was a retrospective analysis
      of deaths caused by RT-PCR-confirmed cases of Influenza A/H1N1 in a tertiary care
      institution in North India from September 2009 until January 2010. RESULTS: Among
      125 patients admitted to the Influenza A/H1N1 ward of the hospital, a total of 16
      deaths had occurred in patients who were positive for Influenza A/H1N1. Two
      deaths were in the paediatric age group. Most patients who died had some
      predisposing illness, such as pregnancy, underlying chronic respiratory illness,
      diabetes, obesity, etc. CONCLUSIONS: In the present study, deaths from Influenza
      A/H1N1, as with seasonal influenza, appeared to occur primarily in individuals
      with underlying illness. In India, such individuals may be considered first for
      preventive strategies, including vaccination.

PMID- 20818098
TI  - Emergence of CTX-M Group 1-ESBL producing Klebsiella pneumonia from a tertiary
      care centre in Karachi, Pakistan.
AB  - BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-producing Klebsiella
      pneumoniae have been reported previously from Pakistan but the genotypic
      characteristics of these enzymes is not known. Hence the aim of the study was
      first to characterise the genotypic content of these beta-lactamases and secondly
      to assess the clonal relationship of these isolates. METHODOLOGY: We analysed 65
      non-duplicate ESBL positive, K. pneumoniae isolates prospectively collected based
      on phenotype as detected using the two-disc method. Isolates were collected from
      different sources: blood cultures (46.15%; n = 30); tracheal aspirates (24.6%; n
      = 16); urine (10.7%; n = 7); wound swabs, pus and tissue (18.4%; n = 12). ESBL
      production was confirmed by the ESBL E-test method and the presence of the blaCTX
      M encoding genes was confirmed by polymerase chain reaction. The clonal
      relationship of clinical isolates was studied by Pulsed Field Gel
      Electrophoresis. RESULTS: The results showed that 93.84% (n = 61) isolates of K.
      pneumoniae were positive for the blaCTX-M-1 group. One isolate showed PCR signals
      for blaCTX-M-25 group. None of our isolates were positive for CTX-M groups 2, 8
      and 9. The majority of blaCTX-M positive isolates were genetically unrelated and
      no epidemic clones were identified. CONCLUSION: This study reports the emergence
      of CTX-M groups 1 and 25 producing isolates of K. pneumoniae with genetic
      diversity in Karachi, Pakistan.

PMID- 20818099
TI  - Plasmid profile and drug resistance pattern of zoonotic Salmonella isolates from
      Indian buffaloes.
AB  - BACKGROUND: Buffalo is the major source of animal protein in south-east Asia,
      including India; therefore, the presence of multiple drug resistance in
      Salmonella strains of buffalo meat and milk products is of immense public health
      concern. METHODOLOGY: Forty-six strains of Salmonella enterica subspecies
      enterica belonging to eight serovars (S. Anatum, 13; S. Weltevreden, 13; S.
      Rostock, 6; S. Typhimurium, 5; S. Gallinarum, 5; S. Stockholm, 1; S. Dublin, 1;
      and S. Orion, 2), isolated from buffalo meat and diseased buffaloes were studied
      for their antibiotic sensitivity and plasmid profile. RESULTS: All except six
      strains of Salmonella had one or more plasmids. Virulence plasmid of ~35MdA was
      present in 39 isolates while 19 strains had one to six additional plasmids with
      molecular weight ranging from 1 Mda > 35 Mda. A plasmid-free S. Anatum strain was
      resistant to seven drugs including fluoroquinolones, while strains having six to
      seven plasmids were resistant to fewer antimicrobial drugs. One S. Anatum
      isolate, resistant to 11 antibiotics, had only one plasmid. Eight serovars of
      Salmonella could be divided into 28 resistotypes on the basis of antimicrobial
      sensitivity assay. Most strains were resistant to streptomycin (84.8%) followed
      by kanamycin (58.7%), gentamicin (52.2%), ampicillin (50%) and oxytetracycline
      (50%). Few strains were resistant to cefotaxime (2.2%), amoxycillin (2.2%) and
      newer fluoroquinolones (6.5%). CONCLUSION: Multiple drug resistance was common
      among Salmonella isolates of buffalo origin, particularly against
      aminoglycosides, oxytetracycin, ampicillin and cephalexin. Presence of plasmids
      is not mandatory for occurrence of multiple drug resistance in S. enterica
      strains.

PMID- 20818100
TI  - Antimicrobial susceptibility and serovars of Salmonella from chickens and humans
      in Ibadan, Nigeria.
AB  - BACKGROUND: This study determines the prevalence and antibiotic resistance of
      Salmonella serovars from humans and chickens in Ibadan, Nigeria, in 2004-2007.
      METHODOLOGY: A total of 991 blood samples were collected from patients in 2004 to
      2005 and 641 fecal samples were collected from poultry farms in 2007. All
      Salmonella isolates were serotyped and tested for antimicrobial susceptibility.
      RESULTS: Thirty-nine (4%) Salmonella isolates were obtained from human blood and
      70 (11%) from chicken fecal samples. The human isolates revealed nine different
      serovars; 82% were non-typhoidal Salmonella and 18% were (S. Typhi). The majority
      of serovars from humans were S. Enteritidis (33%), S. Dublin (18%), and S.
      Typhimurium (18%). Resistance to chloramphenicol, sulfamethoxazole, trimethoprim,
      and ampicillin ranged from 36% to 59% for the human isolates. Eight different
      serovars were obtained from chickens; S. Virchow (71%) predominated. A high
      frequency (87%) of reduced susceptibility to ciprofloxacin was observed among the
      chicken isolates. A high frequency of resistance to tetracycline (93%), nalidixic
      acid (81%), and sulfamethoxazole (87%) was observed. Rare serovars such as S.
      Apapa, S. Mouschaui, S. Jukestown, S. Oritamerin, and S. Onireke were isolated
      from both humans and chickens. Identical serovars were not found among human and
      chicken isolates. CONCLUSIONS: This study indicates that chickens are not a
      reservoir of Salmonella causing bacteraemia among humans in Ibadan, Nigeria.
      Studies locating the reservoirs responsible for invasive salmonellosis in humans
      are needed. Controls and targeted interventions against S. Virchow and the
      frequent occurrence of antimicrobial resistance in chickens should be initiated
      to prevent the spread of this serovar.

PMID- 20818101
TI  - Condom use among antiretroviral therapy patients in Ibadan, Nigeria.
AB  - BACKGROUND: While antiretroviral treatment (ART) has improved the health status
      of people living with HIV, new challenges to their sexual and reproductive health
      (SRH) needs and their ability to prevent secondary HIV infections have risen.
      This study aimed to determine the level and factors that affect condom use among
      ART-experienced patients at the premier teaching hospital in Nigeria.
      METHODOLOGY: This longitudinal study involved patients who initiated treatment at
      the University College Hospital, Ibadan, Nigeria, between January and December
      2006. Sexually active patients who had received treatment for at least six months
      and had not defaulted on clinic follow-up schedules were studied. Data on socio
      demographic characteristics and condom use were extracted from clinic records.
      Chi square test and logistic regression were employed to determine factors
      associated with condom use. RESULTS: The study involved 866 patients,
      specifically, 306 (35.3%) men and 560 (64.7%) women aged 40.7 (SD 7.6) and 33.3
      (SD 6.5) years respectively. Condoms usage before treatment and at last clinic
      visits was 14.0% and 43.3% respectively. Overall reports of condom use at
      specified periods were as follows: 1-6 months (33.0%); 7-12 months (37.3%) and
      above 12 months (53.8%). Patients in a marital union and those with higher
      education were more likely to use condoms. CONCLUSIONS: Condom use is
      significantly influenced by marital status and educational level. Although condom
      use increases together with follow-up time, the level can be improved. Primary
      and secondary prevention efforts targeting high-risk sexual behaviour among ART
      patients need to receive greater and continual attention.

PMID- 20818102
TI  - Clinical profile of dengue fever infection in King Abdul Aziz University Hospital
      Saudi Arabia.
AB  - BACKGROUND: The study aimed to compare the clinical profile of all patients
      diagnosed with dengue viral infection at King Abdul Aziz University Hospital
      (KAAUH), during 2005-2008. METHODOLOGY: This retrospective study included 147
      patients infected with dengue virus, age < or =16 years. Laboratory and
      haematological data were included. RESULTS: Two peaks of infection occurred
      during 2006 and another two in 2008. Common clinical symptoms were fever,
      vomiting, and abdominal pain. Common haematological abnormalities were
      thrombocytopenia and leucopoenia. Differences existed between the years in the
      percentage of patients with fever, elevated alanine aminotransferase (ALT),
      direct bilirubin, lactate dehydrogenase (LDH), fibrin degradation products
      (FDPs), and haemoglobin (Hb) levels. Differences were found in nationalities
      between the years, but patient nationality had no effect on disease incidence.
      Differences were noted in the percentages of patients' immunoglobulin M (IgM) and
      polymerase chain reaction (PCR) positive. There was a slight inverse correlation
      of IgM positive with patient age. PCR, fever, ALT, direct bilirubin, LDH, FDPs,
      Hb, blood transfusion, and platelet transfusion showed no correlation with age or
      nationality. In 2005, all the patients survived, but there were 4.55%, 25%, and
      2.7% deaths during 2006-2008. CONCLUSIONS: Significant differences in the
      clinical presentation of dengue virus (DENV) infection, indicative of a variation
      in disease severity from dengue fever (DF) to dengue hemhorrhagic fever
      (DHF)/dengue shock syndrome (DSS), were noted over the years. Possible reasons
      are infection with different serotypes, concurrent/sequential infection of more
      than one serotype, and differences in host immune responses associated with host
      genetic variations.

PMID- 20818103
TI  - Detection of Aspergillus species in bone marrow transplant patients.
AB  - INTRODUCTION: Invasive aspergillosis is a severe complication of cytotoxic
      chemotherapies and bone marrow transplantation (BMT). The aim of this study was
      to assess the utility of a real-time PCR assay for the early diagnosis of
      Aspergillus species in blood samples from BMT patients. METHODOLOGY: Blood
      specimens (n = 993) from patients (n = 82) scheduled for BMT were collected prior
      to transplant and for 100 days post transplantation. The specimens were later
      tested using an Aspergillus-specific real-time PCR assay. Cultures of clinical
      samples, along with sonography and computerized tomographic scans, were performed
      as standard of care. RESULTS: Aspergillus DNA was positive in 94 sequential blood
      samples from 13 patients with clinical and radiological signs of infection.
      Samples from three of these patients were PCR-positive for Aspergillus in the
      first week of admission, prior to transplantation. Four patients with
      aspergillosis were cured with antifungal agents and nine died. An additional 12
      patients without clinical signs of infection were PCR-positive on one occasion
      each, while two patients with clinical signs of infection were PCR-negative.
      Compared to routine methods of aspergillosis diagnosis, the respective
      sensitivity, specificity, negative, and positive predictive values of the PCR
      method by patient were 86.6%, 82%, 96.5% and 52%. CONCLUSIONS: The results show
      that Aspergillus infections in the blood of bone marrow transplant patients can
      be dectected by PCR methods. Early detection of Aspergillus infections by PCR has
      the potential to positively impact patient mortality rate and provide cost
      savings to hospitals.

PMID- 20818104
TI  - Nosocomial blood-stream infections from extended-spectrum-beta-lactamase
      producing Escherichia coli and Klebsiella pneumonia from GB Pant Hospital, New
      Delhi.
AB  - BACKGROUND: Nosocomial septicemia due to extended spectrum beta-(Beta)-lactamase
      (ESBL) producing Klebsiella pneumoniae and Escherichia coli are a therapeutic
      challenge due to resistance. Knowledge of disease burden and resistance patterns
      is required for proper and timely management. We report the prevalence and
      antimicrobial susceptibility of ESBL producing E. coli and K .pneumoniae from
      septicemia at a tertiary care hospital. METHODOLOGY: A total of 2,870 blood
      samples of suspected cases of septicemia were studied between January and
      December 2009. Antimicrobial susceptibility was determined by Kirby Bauer's disc
      diffusion method and MICs for imipenem, meropenem, and ertapenem were determined
      using the E-test. All isolates of E. coli and K. pneumoniae were tested for ESBL
      production by E-test method. RESULTS: Forty-one (70.7%) K. pneumoniae isolates
      and ten (41.7%) E. coli isolates were ESBL producers. Two (5%) of ESBL producing
      K. pneumoniae isolates, but no E. coli isolates, were resistant to carbapenems.
      In vitro, all ESBL producers were sensitive to tigecycline. CONCLUSION: Our data
      indicated that the prevalence of ESBL-producing E. coli and K. pneumonia strains
      isolated from blood cultures from hospitalized patients is high. ESBL-producing
      organisms were found to be more susceptible to meropenem than to imipenem and
      ertapenem. Tigecycline is active against all the ESBL or multidrug resistant
      (MDR) E. coli and Klebsiella spp. isolates.

PMID- 20818105
TI  - Soft tissue infection due to Mycobacterium fortuitum following acupuncture: a
      case report and review of the literature.
AB  - We report the first case of a post-acupuncture soft tissue infection due to
      Mycobacterium fortuitum. Two months after finishing an acupuncture treatment
      session, an immunocompetent 23-year-old woman developed cellulitis at the side of
      the needle insertions and the acid-fast bacillus was isolated from a closed
      abscess. The patient was successfully treated with a proper drug combination. We
      review the literature concerning the infection source and the risks for skin and
      soft tissue infection due to mycobacteria after acupuncture. The infection source
      in most cases is unknown but is probably associated with the inadequate
      sterilization of the needles or the puncture site. We show that these infections
      are not rare but difficult to diagnose. To avoid delays in the definitive
      diagnosis, infection with mycobacteria should be considered for skin and soft
      tissue infections, in particular late-onset infections, which are negative for
      routine bacterial cultures and without a clinical response to antibiotics used
      for acute pyogenic infections. Bacterial cultures from this lesion should be
      maintained for at least six weeks before discharged as negative.

PMID- 20818106
TI  - Disseminated Cryptococcosis in an HIV-negative patient in South Africa: the
      elusive differential diagnosis.
AB  - The presence of an opportunistic infection in a patient in sub-Saharan Africa is
      assumed to be due to underlying immunosuppression from human immunodeficiency
      virus (HIV) infection. The presence of disseminated cryptococcosis in a non-HIV
      infected patient is interesting as it is unique in our setting because the
      majority of infections are found in HIV-infected individuals. The protean
      manifestations of the disease and its predilection for immunosuppressed patients
      make cryptococcosis a challenging and elusive disease to diagnose in HIV-negative
      patients in our setting, especially due to limited resources. We present a case
      of disseminated cryptococcosis in an immunocompetent patient and discuss
      diagnostic and therapeutic features in this subset of patients.

PMID- 20818107
TI  - Asymptomatic catheter related Rhizobium radiobacter infection in a haploidentical
      hemapoetic stem cell recipient.
AB  - Catheter related infections are reported as one of the most common source of
      nosocomial infections. Rhizobium radibacter infections are generally manifested
      by fever and leukocytosis. Here, a 14 months-old girl diagnosed as T (-) B (-) NK
      (+) severe combined immunodeficiency (SCID) is presented. She had received
      repeated (x3) unconditioned haploidentical hematopoetic stem cell
      transplantations. During the follow-up, she has been arised an asymptomatic
      infection with R. Radiobacter, which was isolated from central venous catheter
      and peripheral blood while she was clinically stable, free of symptoms, fever or
      leukocytosis. She was treated successfully with cefepime and amikacin and did not
      require catheter removal. So, it is once more clear that the blood cultures
      should be obtained on regular basis from all patients with an intravascular
      device, even they were asymptomatic.

PMID- 20818108
TI  - Mass spectrometry based proteomic profiling for pancreatic cancer.

PMID- 20818109
TI  - Contrast enhanced transabdominal ultrasound in the characterisation of pancreatic
      lesions with cystic appearance.
AB  - CONTEXT: Contrast enhanced ultrasound (CEUS) has been established for detection
      and characterisation of liver tumours and differential diagnosis of solid
      pancreatic lesions. The role of transabdominal CEUS in cystic pancreatic disease
      is less obvious. OBJECTIVE: We prospectively evaluated CEUS for characterization
      of undetermined cystic pancreatic lesions with respect to the differential
      diagnosis of pseudocysts and cystic neoplasia and differentiation between benign
      and malignant disease (gold standard: histology or cytology). PATIENTS: One
      hundred and fourteen patients (63 males, 51 females; median age: 62 years, range:
      33-87 years) were prospectively examined. INVESTIGATIONS: Conventional B-mode and
      transabdominal CEUS. MAIN OUTCOME MEASURES: Conventional B-mode (criteria: solid
      nodules, septae), and contrast enhancing features of cystic pancreatic lesions
      (microperfusion of solid nodules) were analysed. Final diagnoses were made by
      surgery (47 patients) or histology/cytology and follow-up of at least one year
      (67 patients). RESULTS: Fifty patients proved to have neoplastic lesions (37
      malignant, 13 of benign origin). Sixty-four patients had pseudocysts caused by
      acute (27 patients) or chronic pancreatitis (37 patients). Conventional B-mode
      had a sensitivity of 94% and a low specificity of 44% in the differentiation of
      pseudocysts versus neoplasia. CEUS had a higher specificity of 77% with the same
      sensitivity of conventional B-mode ultrasound. The combination of conventional
      ultrasound and CEUS improved the specificity even more to 97% with an unchanged
      sensitivity. CEUS was not reliable in the differentiation of benign and malignant
      neoplasia. CONCLUSION: CEUS improves the differentiation between pseudocysts and
      pancreatic neoplasia in comparison to the conventional B-mode imaging. The
      microvascularisation visualised using CEUS even in small nodules (with or without
      septae) associated with cystic lesions is an indicator for cystic pancreatic
      neoplasia.

PMID- 20818110
TI  - Synchronous resection of solitary liver metastases with pancreaticoduodenectomy.
AB  - CONTEXT: There is limited information available about the feasibility and
      benefits of synchronous resection of liver metastases in patients with pancreatic
      and periampullary cancer undergoing pancreaticoduodenectomy. OBJECTIVE: We report
      on our experience with 7 such patients. DESIGN: Analysis of the prospective
      database was carried out to identify patients who underwent synchronous resection
      of liver metastases with pancreaticoduodenectomy. PATIENTS: Two-hundred and
      thirty patients underwent pancreaticoduodenectomy for pancreatic and
      periampullary cancer in our unit between September 2003 and September 2009. MAIN
      OUTCOME MEASURES: The primary aim of our study was to determine the survival
      benefits and the secondary aim was to evaluate their safety and influence on the
      results of a pancreaticoduodenectomy. RESULTS: Seven patients (3%) underwent
      synchronous resection of a solitary liver metastasis. In these patients, the
      operative time and intra-operative blood loss was marginally high as compared to
      the overall cohort of patients undergoing pancreaticoduodenectomy; however, the
      complication rates and the duration of the hospital stay were not affected. In
      patients undergoing resection of liver metastasis, there were 4 recurrences over
      a mean follow-up of 21 months. CONCLUSIONS: In patients with resectable
      pancreatic and periampullary cancer, the resection of a solitary liver metastasis
      can safely be performed together with a pancreaticoduodenectomy; however, its
      impact on improving survival has yet to be proven.

PMID- 20818111
TI  - Impact of pancreatic gland volume on fistula formation after pancreatic tail
      resection.
AB  - CONTEXT: Resection of the body and tail of the pancreas (distal pancreatectomy)
      is associated with high postoperative morbidity, most of which is due to leakage
      from the pancreatic transection surface. OBJECTIVE: The aim of the current study
      was to analyze factors which may affect the risk of pancreatic fistula formation.
      PATIENTS: All consecutive distal pancreatectomies prospectively registered in our
      hospital database from 1999 to 2007 were included. Clinically relevant pancreatic
      fistula grades B and C, defined according to the International Study Group on
      Pancreatic Fistula (ISGPF) definition were assessed. MAIN OUTCOME MEASURES: The
      impact of patient, tumor, surgery, and radiology-related factors on the risk of
      pancreatic fistula formation were assessed by univariate and multivariate
      analyses. RESULTS: A distal pancreatectomy was performed in 51 patients (median
      age: 59 years; range: 26-76 years), 22 of whom had malignant and 29 benign or
      premalignant disease. Pancreatic fistulas were diagnosed in 17 (33.3%) of the
      patients. An additional three patients had a local abscess without apparent but
      assumed pancreatic leakage. Multivariate analysis showed that pancreatic fistulas
      occurred more frequently after hand suturing of the transection area versus the
      use of a stapler (69.2% vs. 21.1%; OR: 40.4, 95% CI: 3.36-486; P=0.004) and a
      large volume of the pancreatic remnant (greater, or equal to, 34 cm3) increased
      the subsequent risk of pancreatic fistula (57.1% vs. 20.8%; OR: 6.14, 95% CI:
      1.14-39.0; P=0.035). CONCLUSIONS: Development of pancreatic fistula after distal
      pancreatectomy remains a challenge. The volume of the remaining pancreas and the
      technique of closure of the transected pancreas were found to affect this risk,
      thus allowing future preventive measures to be explored and evaluated in clinical
      trials.

PMID- 20818112
TI  - Splenic mass and isolated gastric varices: a rare presentation of a
      neuroendocrine tumor of the pancreas.
AB  - CONTEXT: Splenic involvement in neuroendocrine pancreatic tumors is well known
      but rarely presents as a primary splenic mass. CASE REPORT: A rare case of a
      neuroendocrine tumor involving the tail of the pancreas, splenic hilum and
      splenic flexure of the colon, forming a conglomerate mass and presenting as
      isolated gastric varices is described. A 75-year-old male presented with
      hematemesis and melena. Esophagogastroduodenoscopy revealed isolated gastric
      varices. A CT scan revealed a mass predominantly involving the spleen and a small
      part of the pancreas. CONCLUSION: A splenic mass with isolated gastric varices
      should be kept in mind as one of the presentations of a pancreatic neuroendocrine
      tumor.

PMID- 20818113
TI  - Pancreas-preserving duodenal resections with bile and pancreatic duct
      replantation for duodenal dystrophy. Two case reports.
AB  - CONTEXT: Duodenal dystrophy is a rare disease, characterized by the chronic
      inflammation of the aberrant pancreatic tissue in the duodenal wall. CASE
      REPORTS: Two middle-aged men were admitted with upper abdominal pain of several
      months duration, periodic nausea and vomiting after meals, intermittent jaundice
      and weight loss. A diagnosis of cystic dystrophy of the vertical part of the
      duodenum without chronic inflammation of the orthotopic pancreas was established
      in both cases by multi-detector computed tomography, magnetic resonance imaging
      and endosonography. Both patients were successfully treated by two modifications
      of pancreas-preserving duodenal resections with reimplantation of the bile and
      pancreatic ducts into the neoduodenum. CONCLUSION: These cases are a good example
      of a pancreas-preserving approach to duodenal dystrophy treatment and can be an
      alternative to the Whipple procedure in cases of mild changes of the orthotopic
      gland.

PMID- 20818114
TI  - Portal annular pancreas. A rare variant and a new classification.
AB  - CONTEXT: Portal annular pancreas is a rare congenital anomaly resulting from
      fusion of the pancreatic parenchyma around the portal vein/superior mesenteric
      vein. It is asymptomatic, but could have serious consequences during pancreatic
      surgery, if unrecognized. We describe a variant of this anomaly encountered
      during pancreaticoduodenectomy and propose a new classification. CASE REPORT: We
      report a 51-year-old male who underwent a pancreaticoduodenectomy for
      periampullary carcinoma. After division of the pancreatic neck, a sheath of
      tissue was found posterior and extending to the left of the portal vein. When we
      divided this tissue, a large duct was encountered; this duct communicated with
      the main pancreatic duct. On review of the CT images, the main pancreatic duct
      was seen to be passing posterior to the portal vein and a smaller accessory
      pancreatic duct was present anterior to the portal vein. We describe the surgical
      implications. CONCLUSION: This variant of portal annular pancreas has not yet
      been reported during pancreaticoduodenectomy and we propose a new classification
      for this fusion anomaly.

PMID- 20818115
TI  - Acute ischemic pancreatitis following cardiac arrest: a case report.
AB  - CONTEXT: Ischemia is an established cause of acute pancreatitis; however, acute
      pancreatitis has never been reported after cardiac arrest. CASE REPORT: We report
      a case of acute pancreatitis following cardiac arrest with prolonged
      cardiopulmonary resuscitation in a 58-year-old man, the mechanism of which is
      likely to be ischemic. The patient developed severe ischemic encephalopathy,
      leading to death. Possible causes of acute pancreatitis in a context of
      cardiopulmonary resuscitation are discussed. CONCLUSION: In case of abdominal
      distension following cardiac arrest, diagnoses of mesenteric ischemia and acute
      ischemic pancreatitis should be considered. Such digestive complications
      occurring after cardiac arrest probably reflect the severity of the ischemia.

PMID- 20818116
TI  - Magnetic resonance cholangiography with mangafodipir trisodium in Caroli's
      disease with pancreas involvement.
AB  - CONTEXT: Caroli's disease is a rare congenital disorder first described by Caroli
      in 1958. This abnormality consists of non-obstructive, saccular or fusiform
      dilation of the intrahepatic bile ducts resulting in cystic lesions; similar
      abnormalities may also occur in the kidneys and pancreas. CASE REPORT: We
      illustrate the role of enhanced mangafodipir trisodium magnetic resonance imaging
      in a patient with sporadic non-hereditary Caroli's disease associated with
      pancreatic involvement in which mangafodipir trisodium magnetic resonance imaging
      characterized part of the cystic liver lesions as saccular dilations of the
      intrahepatic bile ducts of the left lobe, allowing diagnosis of the disease.
      CONCLUSION: We strongly recommend hepatobiliary magnetic resonance imaging with
      mangafodipir trisodium in such patients.

PMID- 20818117
TI  - Pancreatic heterotopia in the gallbladder associated with chronic cholecystitis:
      a rare combination.
AB  - CONTEXT: Pancreatic heterotopia is a rare pathologic entity, previously reported
      in the stomach, duodenum and jejunum. It is mostly asymptomatic and rarely gives
      rise to complications. Localization of pancreatic heterotopia in the gallbladder
      is extremely rare and can be associated with cholecystitis or
      cholecystolithiasis. CASE REPORT: We herein describe a case of a 39-year-old man
      who presented with biliary type pain with ultrasonographic evidence of a
      gallbladder polyp. Laparoscopic cholecystectomy was performed with uneventful
      recovery. Pathologic examination of the gallbladder detected a heterotopic focus
      of pancreatic tissue in its wall, associated with chronic cholecystitis with no
      gallstones. CONCLUSION: Pancreatic heterotopia of the gallbladder is a very rare
      entity with unknown clinical significance. Awareness of this condition may
      facilitate its recognition which may shed more light on its clinical
      significance.

PMID- 20818118
TI  - Selective whole blood lipoprotein apheresis to prevent pancreatitis in drug
      refractory hypertriglyceridemia.
AB  - CONTEXT: Severe hypertriglyceridemia is a known cause of acute pancreatitis, and
      apheresis treatment, most commonly plasmapheresis, has been used to treat
      patients with drug refractory hypetriglyceridemia for more than 30 years. CASE
      REPORT: We report a case in which a woman with Crohn's disease and type 2
      diabetes mellitus developed recurrent episodes of acute pancreatitis due to
      extreme hypertriglyceridemia. After the initiation of lipoprotein apheresis from
      whole blood, a marked reduction of triglyceride and lipoprotein levels was
      observed. Some inflammatory parameters were increased even if most of the
      cytokines were not detectable, indicating good biocompatibility of the filter.
      CONCLUSIONS: Triglyceride levels were lowered after initiating selective
      lipoprotein apheresis. More importantly, the patient did not experience any
      relapses of pancreatitis after the treatment was started. Hence this treatment is
      feasible in drug refractory hypertiglyceridemia, but the treatment concept needs
      to be tested in additional studies.

PMID- 20818119
TI  - Gastric duplication cyst with macroscopic serosal heterotopic pancreas.
AB  - CONTEXT: Gastric duplication cysts are often associated with microscopic evidence
      of ectopic pancreatic tissue on their submucosal surface and, less commonly, on
      the subserosal surface. CASE REPORT: We present an unusual case of a gastric
      duplication cyst with finger-like projections and a large heterotopic pancreas on
      the serosal surface of the cyst in a 30-year-old female. CONCLUSION: We point out
      the unusual imaging findings which helped in the preoperative diagnosis.

PMID- 20818120
TI  - Symbiotic bacteria induced necrotizing pancreatitis.
AB  - CONTEXT: Intestinal flora and anaerobes are frequently implicated in causing
      infectious necrotizing pancreatitis however Bifidobacterium and Veillonella have
      rarely been isolated as the causative agents. Bifidobacterium and Veillonella are
      commensal anaerobes which reside in gastrointestinal tract and help deconjugate
      bile acids. Bifidobacterium is also frequently used in probiotics. CASE REPORT:
      We present a 68-year-old man who initially presented with gallstone pancreatitis
      but eventually developed Bifidobacterium and Veillonella species induced
      necrotizing pancreatitis and pseudocyst formation. CONCLUSION: Under rare
      circumstances commensal gut flora can turn pathogenic which can lead to life
      threatening morbidity and may even result in mortality.

PMID- 20818121
TI  - Pancreatic actinomycosis as a cause of retroperitoneal fibrosis in a patient with
      chronic pancreatitis. Case report and literature review.
AB  - CONTEXT: Chronic alcoholic pancreatitis is a debilitating disease that is often
      complicated by pseudotumoral changes of the pancreas, retroperitoneal fibrosis,
      and pancreatic cancer. Actinomycosis is an uncommon intra-abdominal infection and
      its association with chronic pancreatitis has been rarely reported. CASE REPORT:
      We present a case of a patient with progressive long standing chronic
      pancreatitis who develops pseudo-tumoural changes and retroperitoneal fibrosis
      associated with actinomycosis. CONCLUSION: This is a rare presentation of
      actinomycosis, posing a diagnostic challenge to the clinician, with important
      therapeutic implications.

PMID- 20818122
TI  - A bizarre abdominal cystic lesion.
AB  - In spite of careful intraoperative precautions and gauze counts, mistakes can
      still occur during surgery. In the case reported, a retained gauze leaved during
      a surgical approach for removing a solid-cystic papillary tumor localized in the
      pancreatic tail, caused both persistent abdominal discomfort and the presence of
      an abdominal cystic lesion at imaging techniques. When a previous operative
      history is present, a foreign body should be taken into account in the
      differential diagnosis of a patient with an intra-abdominal cystic mass. Finally,
      radio-opaque marker should be routinely used by surgeons in order to reach a
      correct diagnosis in operated patients having retained gauze.

PMID- 20818123
TI  - Primary pancreatic lymphoma or secondary involvement: what is the difference?

PMID- 20818124
TI  - Hepatic failure and hepatorenal syndrome secondary to erlotinib: a possible
      etiology of complications in a patient with pancreatic cancer.

PMID- 20818125
TI  - Zollinger-ellison syndrome with subsequent association of insulinoma.

PMID- 20818126
TI  - The impact of pancreatic enzyme supplementation on postprandial responses of
      glucagon-like Peptide-2 in patients with chronic pancreatitis and pancreatic
      exocrine insufficiency.

PMID- 20818127
TI  - Management of acute pancreatitis: "PANCREAS" contains eight easy steps to
      remember the treatment.

PMID- 20818128
TI  - What is the effectiveness of drug-eluting stents in the treatment of ST-elevation
      myocardial infarction? - should drug-eluting stents be indicated for patients
      with acute coronary syndrome? (Pro) -.
AB  - The effective use of drug-eluting stents (DES) in the treatment of ST-elevation
      myocardial infarction (STEMI), a condition representative of acute coronary
      syndrome, has not been clarified, particularly among Japanese patients. The
      indication of DES for STEMI patients is discussed by reviewing the evidence from
      both Western countries and Japan. Currently, in the registry studies, randomized
      studies, and meta-analyses comparing the use of DES and bare-metal stents (BMS)
      in STEMI patients, DES show a consistent trend toward decreasing the risk of
      repeat revascularization without increasing the incidence of death, recurrent MI
      or stent thrombosis when compared with BMS in the treatment for patients with
      STEMI. Japanese data are also consistent with this trend. However, there are no
      clear data indicating safety concerns. Longer-term follow-up studies are
      necessary to assess the effectiveness of DES in STEMI patients.

PMID- 20818129
TI  - Drug-eluting stents are not indicated for patients with acute coronary syndrome -
      should drug-eluting stents be indicated for patients with acute coronary
      syndrome? (Con) -.
AB  - Drug-eluting stents (DES) have been proven to reduce the rate of restenosis by
      marked inhibition of neointimal hyperplasia, but unusual vessel responses to DES,
      such as substantially impaired arterial healing characterized by incomplete
      endothelialization and persistent inflammatory response, have been recognized.
      The culprit sites in acute coronary syndrome (ACS), especially acute myocardial
      infarction, have large necrotic cores with a paucity of smooth muscle cells. In
      these lesions, penetration of the stent struts into the necrotic core is
      frequently observed after stent implantation. Pathologic observations have
      revealed that the lesions stented with DES frequently show greater delay in
      arterial healing than those treated with bare-metal stents. Thus, ACS culprit
      sites could be at persistent risk for thrombosis after DES implantation.

PMID- 20818130
TI  - Right ventricular infarction and tissue Doppler imaging - insights from acute
      inferior myocardial infarction after primary coronary intervention -.
AB  - BACKGROUND: Tissue Doppler imaging (TDI) data for acute inferior myocardial
      infarction (MI) patients who have received primary percutaneous coronary
      intervention (PCI) are sparse. METHODS AND RESULTS: One hundred and sixty-five
      patients received primary PCI for acute inferior MI were enrolled. Right
      ventricular infarction (RVI) was defined as a culprit lesion proximal to the
      right ventricular branch of right coronary artery (RCA). Echocardiograms and TDI
      were obtained within 6 h after primary PCI. The prevalence of multi-vessel
      disease in the RCA-P culprit group (50%) was higher than that in other groups
      (39% of RCA-D culprit, 43% of left circumflex artery (LCX) culprit). The
      myocardial performance index (MPI) of the lateral tricuspid annulus provides
      discriminatory power for identifying RVI, whereas systolic velocity (Sm) of the
      lateral tricuspid annulus does not. Lateral mitral annular MPI divided by the
      lateral tricuspid annular MPI is a reliable index for identifying a culprit
      lesion (>1.06 predicts culprit over LCX; <0.96 predicts culprit over RCA-P and
      RVI). Kaplan-Meier survival curves revealed that late cardiovascular events were
      more likely in RVI patients. However, multivariate Cox proportional hazards
      analysis revealed that the most important factor in hard events and all
      cardiovascular events was multivessel disease. CONCLUSIONS: TDI is useful for
      identifying RVI and culprit lesions in inferior MI patients received primary PCI.
      RVI itself isn't associated with 1-year hard events and all cardiovascular
      events.

PMID- 20818131
TI  - Abnormal myocardial capillary density in apical hypertrophic cardiomyopathy can
      be assessed by myocardial contrast echocardiography.
AB  - BACKGROUND: Myocardial ischemia and dysfunction can occur in hypertrophic
      cardiomyopathy (HCM) because of the high muscle-to-blood ratio, even without
      significant coronary artery disease. Microbubbles reside only in the
      intravascular space and myocardial video-intensity during systole results mostly
      from microbubbles within capillaries. The hypothesis explored in the present
      study was that an abnormal capillary density in apical HCM (ApHCM) can be
      demonstrated using myocardial contrast echocardiography (MCE). METHODS AND
      RESULTS: The 56 patients were investigated (31 males, age 58 +/- 9 years; 33
      ApHCM, 9 hypertensive left ventricular hypertrophy [LVH], 14 controls). MCE was
      performed with low-mechanical-index power modulation imaging. Tissue Doppler
      imaging to assess myocardial contractile function was obtained at the mitral
      annulus (S'), and (99 m)Tc-MIBI SPECT was also performed. All ApHCM patients
      exhibited perfusion defects at the hypertrophied segments in the systolic phase
      during MCE, whereas SPECT showed normal or rather increased perfusion at those
      sites. The cyclic variation of video-intensity was exaggerated in ApHCM when
      compared with the LVH or control group (% of [systolic video
      intensity]/[diastolic video-intensity]: 33.0 +/- 12.3%, 88.3 +/- 19.2% and 79.4
      +/- 13.9%, respectively [P<0.05]). Concurrently, MCE cyclic variation and
      perfusion defect size were related to decreased S' (P<0.05 for all). CONCLUSIONS:
      A perfusion defect at the hypertrophied segment, representing abnormal myocardial
      capillary density, was observed in ApHCM patients during MCE. The extent of MCE
      cyclic variation and the perfusion defect size both correlate with decreased
      myocardial contractile property in ApHCM. 

PMID- 20818132
TI  - Preoperative left atrial mechanical dysfunction predicts postoperative atrial
      fibrillation after coronary artery bypass graft operation - a velocity vector
      imaging-based study -.
AB  - BACKGROUND: The aim of the present study was to evaluate pre-existent subclinical
      mechanical atrial dysfunction in patients with postoperative atrial fibrillation
      (POAF) by using novel echocardiographic techniques. METHODS AND RESULTS: Ninety
      six patients with sinus rhythm, undergoing coronary artery bypass graft (CABG)
      operation were prospectively enrolled. Preoperative left atrial (LA) reservoir,
      conduit and booster functions were evaluated by 3 different methods: conventional
      echocardiography, tissue Doppler imaging (TDI), and 2-dimensional strain imaging
      based-velocity vector imaging (VVI). POAF occurred in 25 out of 96 patients
      (26%). LA volume index (LAVI) was the only conventional parameter associated with
      POAF. TDI-derived LA velocities were similar in study groups. In VVI analysis, LA
      systolic strain, strain rate (SRs) and early diastolic strain rate (ESRd) were
      impaired in patients who developed POAF after CABG (P=0.0001). Age, LAVI, LA peak
      systolic strain, SRs and ESRd were found to be the independent predictors of
      POAF. The optimal cut-off point of 44.0% (88.7% sensitivity, 96% specificity) for
      LA strain, 1.7 s(-1) (88% sensitivity, 86.2% specificity) for SRs and 1.95 s(-1)
      (sensitivity 72%, 70.4% specificity) for ESRd predicted POAF in this study.
      CONCLUSIONS: VVI-derived strain imaging could be used as an adjunctive non
      invasive method for evaluating subclinical atrial mechanical dysfunction in
      patients undergoing CABG. This might help us to identify patients with high risk
      of POAF in clinical practice. 

PMID- 20818133
TI  - Indoxyl sulfate stimulates monocyte chemoattractant protein-1 expression in human
      umbilical vein endothelial cells by inducing oxidative stress through activation
      of the NADPH oxidase-nuclear factor-kappaB pathway.
AB  - BACKGROUND: Chronic kidney disease (CKD) is recognized as a common condition that
      elevates the risk of atherosclerotic cardiovascular disease (CVD). Evidence
      suggests that increased oxidative stress is an emerging key mechanism of
      atherosclerosis in CKD. One recent study reported that indoxyl sulfate (IS), a
      uremic toxin derived from dietary protein, could cause vascular disorder,
      however, little is known about the mechanism involved. The present study examined
      the signaling pathway that is activated by IS to induce monocyte chemoattractant
      protein-1 (MCP-1), which plays an important role in the development of
      atherosclerosis, in cultured human umbilical vein endothelial cells (HUVEC).
      METHODS AND RESULTS: We show that IS enhanced reactive oxygen species (ROS)
      production, assessed by dihydroethidium staining, by HUVEC. IS also induced the
      expression of MCP-1, which was measured by enzyme-linked immunosorbent assay and
      real-time reverse transcription-polymerase chain reaction. These changes were
      suppressed by apocynin, a specific inhibitor of NADPH oxidase. Furthermore, IS
      induced the expression of NADPH oxidase 4 (Nox4) mRNA. IS-induced stimulation of
      ERK1/2 and p38 phosphorylation, detected by immunoblotting, was inhibited by
      apocynin. Finally, IS activated NF-kappaB, which was suppressed by inhibiting
      ERK1/2 and p38, resulting in reduced MCP-1 expression. These results suggest that
      IS increases NADPH oxidase-derived ROS, which in turn, activates the MAPK/NF
      kappaB pathway and leads to induction of MCP-1 expression in HUVEC. CONCLUSIONS:
      These findings raise the possibility that IS plays an important
      pathophysiological role in the development of CVD in individuals with CKD.

PMID- 20818134
TI  - Circulating adiponectin level is associated with major adverse cardiovascular
      events in type 2 diabetic patients with coronary artery disease.
AB  - Elevated levels of circulating adiponectin (ADPN), an anti- inflammatory and anti
      oxidative peptide, are associated with unfavorable cardiovascular outcomes in
      patients with cardiovascular diseases. The aim of this study was to investigate
      whether plasma ADPN levels could help predict major adverse cardiovascular events
      (MACE) in patients with documented coronary artery disease (CAD). We
      prospectively enrolled 193 CAD patients, who underwent percutaneous coronary
      intervention (PCI), and/or stenting and coronary artery bypass graft (CABG)
      surgery. ELISA was used to measure plasma ADPN concentrations. MACE--myocardial
      infarction, PCI, CABG, stroke, carotid revascularization, and death--was
      evaluated during a follow-up period of median 15.3 months (range 5-21 months).
      Cox regression analysis revealed that diabetes status, waist circumference, and
      plasma ADPN levels were significantly associated with MACE occurrence. On
      stratification according to diabetes status, plasma ADPN levels helped predict
      MACE only in patients with type 2 diabetes mellitus (T2DM). Kaplan-Meier analysis
      revealed higher MACE rates in diabetic patients with high-plasma ADPN levels than
      in those with low-plasma ADPN levels. High ADPN plasma concentrations can
      independently be associated with MACE in CAD with T2DM but not in those without
      diabetes. This indicates that plasma ADPN may have potential roles in high risk
      T2DM patients with ischemic heart disease.

PMID- 20818135
TI  - Working memory processing for human voice perception in a patient with mild
      cognitive impairment: an FMRI study.

PMID- 20818136
TI  - Efficacy of transurethral resection of the bladder tumor (TUR-BT) for huge
      bladder cancer.
AB  - There are no guidelines regarding whether to perform either a radical
      transurethral resection of the bladder tumor (TUR-BT) or a total cystectomy after
      TUR biopsy for huge bladder cancer, and this decision is entrusted to each
      institution. Of 439 patients in whom TUR-BT was performed from 2005 through 2009,
      the weight of the total resected volume was > 50 g in 6 patients, and among these
      6 patients the following variables were compared: operating time, weight of
      resected volume, transfusion volume, presence or absence of hydronephrosis,
      preoperative urinary cytology, serum cytokeratin 19 fragment (CYFRA) level,
      intraoperative bladder compliance, and histopathological findings. The median
      age, operating time, weight of resected volume, transfusion volume, and length of
      follow-up were 72 years, 300 minutes, 88 g, 202 mL, 16 months, respectively. The
      serum CYFRA level in patients with muscle-invasive cancer (11.8 ng/mL) was higher
      than that in patients with non-muscle-invasive cancer (5.06 ng/mL). All patients
      with non-muscle-invasive bladder cancer survived without recurrence. Although the
      mean length of follow-up was only 16 months (5-59 months), the 1 patient who was
      followed up for 59 months had no recurrence. In cases of muscle-invasive bladder
      cancer, all patients, except for a relatively recent patient, have died. In cases
      without muscle invasion, lymph node metastasis, distal metastasis, or
      preoperative renal dysfunction accompanied by hydronephrosis, with favorable
      bladder compliance, we believe that radical TUR-BT should be actively performed
      to preserve the bladder. A second TUR-BT should be performed in cases of non
      muscle-invasive cancer without G3 components to treat the huge bladder cancer.

PMID- 20818137
TI  - Total colonoscopy detects early colorectal cancer more frequently than advanced
      colorectal cancer in patients with fecal occult blood.
AB  - The efficacy of total colonoscopy following a positive result of the fecal occult
      blood test (FOBT) for the early detection of colorectal cancer and polyps was
      evaluated. A total of 1,491 patients with positive FOBT results underwent total
      colonoscopy at the Institute of Gastroenterology, Nippon Medical School, Musashi
      Kosugi Hospital, from April 2002 through July 2009. Abnormalities were found in
      1,312 of the 1,491 patients (88.0%). Ninety-six of the 1,491 patients (6.4%) were
      found to have early cancer, but 59 patients (4.0%) were found to have advanced
      cancer. The early cancers were treated with endoscopic mucosal resection or
      endoscopic submucosal dissection in 81 patients, with laparoscopy-assisted
      colectomy in 10 patients, and with open surgery in 5 patients. Fifty-one of the
      59 patients with advanced colorectal cancer underwent conventional open surgery,
      and 8 patients underwent laparoscopic surgery. The cancers detected were more
      likely to be early cancers than advanced cancers. In addition to malignancies,
      other abnormalities found included inner or external hemorrhoids, diverticula of
      the colon, ulcerative colitis, ischemic colitis, infectious colitis, and
      colorectal polyps. Our results show that a high percentage of lesions detected
      with total colonoscopy following a positive FOBT result are early colorectal
      cancers and polyps.

PMID- 20818138
TI  - Clinical significance of singleton pregnancies complicated by placental abruption
      associated with histological chorioamnionitis.
AB  - The aim of this study was to determine the perinatal outcomes of placental
      abruption associated with the presence of histological chorioamnionitis. We
      reviewed the obstetric records of 96 singleton deliveries complicated by
      placental abruption after 22 weeks' gestation. Of these 96 cases, 37 cases (39%)
      were diagnosed as having histological chorioamnionitis in the placenta. The
      incidence of premature delivery, preterm rupture of the membranes and low birth
      weight in the cases of placental abruption with chorioamnionitis were higher than
      in cases without chorioamnionitis. However, there were no significant differences
      in the incidence of other outcomes, such as fetal demise, low Apgar score, or low
      umbilical artery pH, between the cases of placental abruption with and without
      histological chorioamnionitis. Although the incidence of prematurity in the cases
      of placental abruption with chorioamnionitis was higher than that in cases
      without chorioamnionitis, there were no significant differences in fetal and
      neonatal conditions between the abruption cases with and without
      chorioamnionitis.

PMID- 20818139
TI  - A training session in a clinical simulation laboratory for the acquisition of
      clinical skills by newly recruited medical interns.
AB  - In organized orientation programs for newly recruited medical interns of the
      Nippon Medical School Hospital, the working committee of the clinical simulation
      laboratory introduced a laboratory training session that was designed to improve
      the clinical skills of the medical interns. The session consisted of 6 training
      courses, comprising internal examination, tracheal intubation, auscultation of
      heart sounds, bandaging and the collection of samples of venous and arterial
      blood. Medical interns rotated to a new course every 30 minutes and did practical
      trainings in each of the 6 skills. A total of 36 newly recruited medical interns
      participated in the training session. The majority of medical interns took part
      in the practical training actively and positively. The session was efficiently
      carried out from the standpoints of human resources and the teaching hours
      involved. A post training questionnaire survey, completed by the medical interns,
      revealed that many of them valued the sessions for comprehensibility of the
      instructions, the descriptions in the manual and the content of the training;
      however, only 21% thought that they had successfully acquired the clinical
      skills. Medical interns must continually engage in self-training to steadily
      acquire basic clinical skills. The convenience of a clinical simulation
      laboratory, together with the reinforcement of the education of clinical skills
      during internship, is necessary to strengthen the educational benefits of the
      training session.

PMID- 20818140
TI  - Merkel cell carcinoma on the upper lip of a 100-year-old woman.
AB  - Merkel cell carcinoma (MCC) is a rare skin tumor that usually occurs on the head,
      neck, or extremities of elderly patients; it has a high incidence of local
      recurrence, regional lymph node metastasis, and subsequent distant metastasis. We
      report a MCC that developed rapidly on the left corner of the upper lip of a 100
      year-old woman. An incisional skin biopsy was performed to confirm MCC. Computed
      tomography showed no metastasis. The tumor was widely excised with a margin of 1
      cm. Immediate reconstruction with a reverse Estlander flap from the lower lip was
      performed under general anesthesia. Additional surgery was also performed under
      general anesthesia 2 weeks later to widen the patient's lips. The surgical
      results were satisfactory. The patient died of senile deterioration a year after
      hospitalization for long-term medical treatment, without any recurrence or
      metastasis of MCC. Despite the patient's age, we considered it necessary to
      resect the tumor widely because of its rapid growth. The tumor margin was 1 cm.
      No radiotherapy was performed, but we believe that surgery alone was effective in
      allowing this patient to live an additional year without recurrence or
      metastasis. To the best of our knowledge, this patient is the oldest person with
      MCC yet described.

PMID- 20818141
TI  - A case of commotio cordis caused by steering wheel injury.
AB  - We report a rare case of commotio cordis caused by traffic injury. The patient
      was a 60-year-old female driver who suffered severe steering wheel impact to the
      chest during a head-on collision in which her car overturned. She had no history
      of cardiac disease. Emergency medical services arrived at the scene within 12
      minutes of the accident. Evidence of ventricular fibrillation led the paramedics
      to carry out immediate defibrillation with an automated external defibrillator.
      Restoration of spontaneous circulation was confirmed within 2 minutes, along with
      establishment of sinus rhythm and normal wave form on electrocardiography. The
      patient was transported to our hospital in an emergency helicopter. General
      examination revealed chest bruising, and computed tomography of the chest showed
      pulmonary contusions; there was no other evidence of critical injury. We
      performed endotracheal intubation, as the patient had consciousness disturbance,
      and then initiated hypothermic therapy in the intensive care unit. Meanwhile, the
      hemodynamics remained stable, and there was no recurrence of arrhythmia. On day
      15, the patient's consciousness improved, and she was able to communicate. Two
      months later, she was transported to another hospital for rehabilitation.

PMID- 20818142
TI  - Syringomyelia associated with Chiari I malformation treated with foramen magnum
      decompression and duraplasty using a polyglycolic acid patch and fibrin glue: a
      case report.
AB  - A 31-year-old woman presented with worsening numbness and pain in the arms and
      chest. Neurological findings at admission were decreased pain sensation and
      temperature sensation in the arms and chest. Magnetic resonance demonstrated a
      large cervical syrinx from the level of C4 to Th4 associated with Chiari I
      malformation. Occipital craniectomy and C1 laminectomy were performed for foramen
      magnum decompression. Intraoperative ultrasonography, performed after removal of
      the outer membrane of the dura mater at the level of the foramen magnum, revealed
      insufficient decompression. Therefore, the dura mater was completely opened and
      duraplasty was performed with a polyglycolic acid patch and fibrin glue.
      Sufficient decompression was thus achieved. The neurological symptoms and signs
      improved within the first postoperative month, and magnetic resonance showed a
      decrease in the size of the syrinx and no cerebrospinal fluid leakage. In
      patients undergoing foramen magnum decompression with duraplasty, the use of a
      polyglycolic acid patch and fibrin glue renders suturing unnecessary and avoids
      the common complications associated with suture duraplasty.

PMID- 20818143
TI  - Recovery from peripartum cardiomyopathy in a Japanese woman after administration
      of bromocriptine as a new treatment option.
AB  - Peripartum cardiomyopathy (PPCM) is a form of heart failure that occurs in women
      within 1 month before delivery and 5 months after delivery. The outcome of PPCM
      is variable but improves significantly when appropriate medication is
      administered in the acute phase; furthermore, the outcome does not worsen even
      after discontinuation of therapy in the chronic phase. The symptoms and signs of
      PPCM are similar to those of idiopathic dilated cardiomyopathy. The medical
      management of patients with PPCM is similar to that for other other forms of
      heart failure. Recent experimental data implicate a casual role of prolactin in
      the development of PPCM. Prolactin secretion can be reduced with bromocriptine
      which had beneficial effects in a small study. We present a Japanese woman with
      acute PPCM treated with bromocriptine as a therapeutic option. Following
      treatment, the serum prolactin levels dropped swiftly. Concurrently, LV function
      improved, and heart failure symptoms decreased, accompanied by a decrease in the
      BNP level.

PMID- 20818144
TI  - [Pathogenesis of cutaneous lupus erythematosus from LE-prone mice].
AB  - Mouse models are similar but not identical to human diseases. However, they are
      important for research into the pathogenesis underlying autoimmune diseases
      because they allow us to evaluate similarities and differences between human
      diseases and mouse models. There are many inbred strains of systemic lupus
      erythematosus (SLE)-prone mice including New Zealand Black (NZB), F1 hybrids of
      NZB x New Zealand White (NZW) (B/W F1), MRL/Mp-lpr/lpr (MRL/lpr), and BXSB mice.
      The postulated etiology of these murine diseases includes many genetic and
      extrinsic factors such as retroviruses, an impaired balance of T cell
      interaction, ultraviolet irradiation, etc. For examples, genetic studies of
      MRL/lpr mice revealed that the appearance of macroscopic LE-like skin lesions
      needs the lpr mutation plus an additional factor in an autosomal dominant
      fashion. The candidate is ultraviolet (UV) B light, the susceptibility to which
      is regulated by the genetic background. Such abnormalities described in SLE now
      span the spectrum from innate immunity to acquired immunity. In this review,
      based on historical review, we focus on skin lesions from the well-studied
      MRL/lpr and B/W F1 mouse and discuss how SLE-prone mice can contribute to a
      better understanding of cutaneous LE pathogenesis.

PMID- 20818145
TI  - [Recent advances in the roles of dendritic cells on contact dermatitis].
AB  - Dendritic cells are one of antigen presenting cells and are thought to play an
      important role in the establishment of immune responses. However, recent advances
      in immunology have revealed that there exist several dendritic cell subsets in
      the skin. In addition, a certain dendritic cell subset is able to regulate
      cutaneous immune responses. We used contact hypersensitivity as a cutaneous
      immune response model and review the recent advances in the roles of dendritic
      cells in contact hypersensitivity.

PMID- 20818146
TI  - [Molecular network analysis of multiple sclerosis brain lesion proteome].
AB  - A recent proteomics study of multiple sclerosis (MS) brain lesion-specific
      proteome profiling clearly revealed a pivotal role of coagulation cascade
      proteins in chronic active demyelination (Han MH et al. Nature 451 : 1076-1081,
      2008). However, among thousands of proteins identified, nearly all of remaining
      proteins were left behind to be characterized in terms of their implications in
      MS brain lesion development. By the systems biology approach using four different
      pathway analysis tools of bioinformatics, we studied molecular networks and
      pathways of the proteome dataset of acute plaque (AP), chronic active plaque
      (CAP), and chronic plaque (CP). The database search on KEGG and PANTHER indicated
      the relevance of extracellular matrix (ECM)-mediated focal adhesion and integrin
      signaling to CAP and CP proteome. IPA identified the network constructed with a
      wide range of ECM components as one of the networks highly relevant to CAP
      proteome. KeyMolnet disclosed a central role of the complex interaction among
      diverse cytokine signaling pathways in brain lesion development at all disease
      stages, as well as a role of integrin signaling in CAP and CP. Although four
      distinct platforms produced diverse results, they commonly suggested a role of
      ECM and integrin signaling in development of chronic lesions of MS. These
      observations indicate that the selective blockade of the interaction between ECM
      and integrins would be a rational approach for designing inhibitors of chronic
      inflammatory demyelination in MS brain lesions.

PMID- 20818147
TI  - [Role of CD69 in the pathogenesis of inflammation].
AB  - CD69 is a type II membrane protein expressed as a homodimer composed of heavily
      glycosylated subunits. CD69 is known as an early activation marker antigen of
      lymphocytes,and its selective expression in inflammatory infiltrates suggests
      that it plays a role in the pathogenesis of inflammatory diseases. In order to
      address the role of CD69 in the pathogenesis of arthritis and allergic airway
      inflammation, we established CD69-deficient mice. CD69-deficient mice displayed a
      markedly attenuated arthritic inflammatory response and airway inflammation. The
      administration of anti-CD69 antibody inhibited the induction of the antigen
      induced airway inflammation and hyperresponsiveness. These results indicate that
      CD69 plays a crucial role in the pathogenesis of arthritis and allergic airway
      inflammation and that CD69 could be a possible therapeutic target for arthritis
      and asthma in human patients.

PMID- 20818148
TI  - [IPEX syndrome and human Treg cells].
AB  - CD4(+)CD25(+) T cells which have also been described as regulatory T cells
      (Treg), have immune inhibitory functions in the immune system. This population
      inhibits excessive immune responses, such as those present in patients with
      autoimmune disease, allergy and inflammation, and plays an important role in
      maintenance of immunological homeostasis. It has been demonstrated that the FOXP3
      gene is a master gene for a transcriptional factor of Tregs. This finding has led
      to the elucidation of the Treg functions during development, differentiation and
      immune suppression. Either a deficiency or dysfunction of Tregs results in IPEX
      (immune dysregulation, polyendocrinopathy, enteropathy, and X-linked) syndrome.
      The clinical features of IPEX syndrome include chronic dermatitis, enteropathy
      characterized by severe and refractory diarrhea, and autoimmune endocrinopathy,
      such as early-onset insulin-dependent diabetes mellitus, thyroiditis, or both.
      This syndrome is also associated with various symptoms such as anemia,
      thrombocytopenia and nephritis which may be caused by an autoimmune response. We
      herein describe the clinical and molecular characteristics of patients with IPEX
      syndrome and also elucidate the function of human Treg cells.

PMID- 20818149
TI  - [Detection of specific markers: our research on the marker in patients with
      Kawasaki disease].
AB  - Anti-endothelial cell antibodies (AECA) were antibodies targeting the antigens
      expressed on the endothelial cell surface. It has been reported that AECA were
      detected frequently in patients with vasculitis and were associated with disease
      activity and vasculitis symptoms. Consequently, AECA are thought to be involved
      in pathophysiology of vasculitis, including Kawasaki disease (KD); however, the
      role of AECA is not clear yet. One of the causes is that target proteins of AECA
      have been poorly identified. Therefore, we try to detect new target proteins of
      AECA in patients with vasculitis using proteomics. We have identified 63 proteins
      out of about 150 endothelial cell-specific candidate target proteins of AECA in
      patients with vasculitis so far. One of the identified proteins was
      peroxiredoxin2 (Prx2), an antioxidant enzyme. Our research suggests that the anti
      Prx2 antibodies are detected frequently in patients with vasculitis and may have
      pathogenic roles in vasculitis via inflammatory cytokines/chemokines production
      and inhibition of anti-oxidative activity of Prx2. In this paper, we overview our
      study of the autoantigens detected by AECA in patients with vasculitis, and will
      provide some data on clinical significance of autoantibodies to Prx2, a target
      protein of AECA, in patients with KD.

PMID- 20818150
TI  - [Th17 cells and human arthritic diseases].
AB  - Th17 cells, though having been discovered just few years ago, is believed as the
      pathogenic T cells in many autoimmune diseases and chronic inflammatory diseases,
      such as rheumatoid arthritis (RA). Biologics targeting IL-17 have already been on
      clinical trial, and the results were recently reported. Although the importance
      of Th17 cells in animal models of arthritis is unquestionable, it is not
      recognized that there are only limited data on the role of Th17 cells and related
      cytokines in human arthritic diseases. In addition, the characteristics of human
      Th17 cells have not been fully defined, and there seem to be substantial
      differences between human and mouse Th17 cells. In this review, I will introduce
      and discuss about updated findings on human Th17 cells and its relation with
      human arthritic diseases.

PMID- 20818151
TI  - [Analysis of epitopes and function of anti-M3 muscarinic acetylcholine receptor
      antibodies in patients with Sjogren's syndrome].
AB  - Sjogren's syndrome (SS) is an autoimmune disease that affects exocrine glands
      including salivary and lacrimal glands. It is characterized by lymphocytic
      infiltration into exocrine glands, leading to dry mouth and eyes. A number of
      auto-antibodies, such as anti-SS-A and SS-B antibodies, are detected in patients
      with SS. However, no SS-specific pathologic auto-antibodies have yet been found
      in this condition. M3 muscarinic acetylcholine receptor (M3R) plays a crucial
      role in the secretion of saliva from salivary glands. It is reported that some
      patients with SS carried inhibitory auto-antibodies against M3R. To clarify the
      epitopes and function of anti-M3R antibodies in SS, we examined antibodies to the
      extracellular domains (N terminal region, the first, second, and third
      extracellular loop) of M3R by ELISA using synthesized peptide antigens encoding
      these domains in 42 SS and 42 healthy controls (HC). Titers and positivity of
      anti-M3R antibodies to every extracellular domain of M3R were significantly
      higher in SS than in HC. For functional analysis, human salivary gland (HSG)
      cells were pre-cultured with IgG from anti-M3R antibodies positive SS, negative
      SS, and HC. HSG cells were stimulated with cevimeline hydrochloride and
      intracellular calcium concentration ([Ca(2+)](i)) was measured. IgG from anti-M3R
      antibodies to the second loop positive SS inhibited the increase of [Ca(2+)](i),
      but IgG from antibodies to the N terminal or the first loop positive SS enhanced
      it, while IgG from antibodies to the third loop positive SS showed no effect on
      [Ca(2+)](i) as well as IgG from anti-M3R antibodies negative SS and HC. These
      findings indicated the presence of several B cell epitopes on M3R in SS and
      effect of anti-M3R antibodies on the salivary secretion might differ with these
      epitopes.

PMID- 20818152
TI  - Secretion of inhibin during the estrous cycle in the female Asian elephant
      (Elephas maximus).
AB  - To define the source of circulating inhibin in female Asian elephants, the
      immunolocalizations of the inhibin alpha, beta(A) and beta(B) subunits, 3beta
      hydroxysteroid dehydrogenase (3beta-HSD), aromatase cytochrome P450 (P450arom)
      and cytochrome 17alpha-hydroxylase P450 (P450 c17) were investigated.
      Concentrations of immunoreactive (ir-) inhibin, progesterone and follicle
      stimulating hormone (FSH) during the estrous cycle were measured by
      radioimmunoassay. Inhibin immunoreactivity in follicular fluid and homogenate of
      corpora lutea was also measured. Immunolocalizations of inhibin subunits, 3beta
      HSD, P450arom and P450c17 were detected in the granulosa cells of antral
      follicles and luteal cells. The follicular fluid contained high levels of ir
      inhibin and bioactive inhibin. The homogenate of corpora lutea also contained ir
      inhibin. Serum ir-inhibin remained at low levels during the early non-luteal
      phase, began to increase from the late non-luteal phase and continued to increase
      during the early luteal phase. Serum ir-inhibin showed maximal levels in the
      middle of the luteal phase and gradually decreased to baseline three weeks prior
      to progesterone decline. The serum ir-inhibin levels were positively correlated
      with progesterone throughout the estrous cycle. On the other hand, ir-inhibin was
      negatively correlated with FSH during the late non-luteal and early luteal
      phases. These findings strongly suggest that the corpus luteum is one of the
      sources of inhibin as well as granulosa cells in the Asian elephant.

PMID- 20818153
TI  - Laforin in autophagy: a possible link between carbohydrate and protein in Lafora
      disease?
AB  - The progressive myoclonus epilepsy of Lafora disease (LD) is a fatal form of
      neurodegenerative disorder associated with progressive intellectual decline and
      ataxia in addition to epilepsy. The disease can be caused by defects in the EPM2A
      gene encoding laforin phosphatase or the NHLRC1 gene encoding malin ubiquitin
      ligase. Laforin and malin function together as a complex in the ubiquitin
      proteasome system, and hence defects in proteolytic processes are thought to
      underlie some of the symptoms in LD. One of the pathological hallmarks of LD is
      the presence of cytoplasmic polyglucosan inclusions, the Lafora bodies. While
      Lafora bodies are known as a lesser branched form of glycogen with high phosphate
      content, a physiological basis for their genesis in the cytoplasm was not well
      understood. Recently it was shown in a mouse model for LD that loss of laforin
      inhibits autophagosome formation, suggesting that laforin plays a critical role
      in autophagosome biogenesis. The polyglucosan inclusions could be one of the
      substrates of autophagy, and loss of laforin might affect their sequestration
      into autophagosomes leading to their aggregation as Lafora bodies. Thus,
      laforin's proposed role in autophagy suggests a possible link between the
      proteolytic system and the polyglucosan inclusions in LD.

PMID- 20818154
TI  - Acto-myosin based response to stiffness and rigidity sensing.
AB  - Cells sense the rigidity of their environment and respond to it. Most studies
      have been focused on the role of adhesion complexes in rigidity sensing. In
      particular, it has been clearly shown that proteins of the adhesion complexes
      were stretch-sensitive, and could thus trigger mechano-chemical signaling in
      response to applied forces. In order to understand how this local mechano
      sensitivity could be coordinated at the cell scale, we have recently carried out
      single cell traction force measurements on springs of varying stiffness. We found
      that contractility at the cell scale (force, speed of contraction, mechanical
      power) was indeed adapted to external stiffness, and reflected ATPase activity of
      non-muscle myosin II and acto-myosin response to load. Here we suggest a scenario
      of rigidity sensing where local adhesions sensitivity to force could be
      coordinated by adaptation of the acto-myosin dependent cortical tension at the
      global cell scale. Such a scenario could explain how spreading and migration are
      oriented by the rigidity of the cell environment.

PMID- 20818155
TI  - The Lrs4-Csm1 monopolin complex associates with kinetochores during anaphase and
      is required for accurate chromosome segregation.
AB  - Lrs4 and Csm1, components of the monopolin complex, localize to the rDNA where
      they regulate rDNA maintenance and segregation. During meiosis, the complex also
      associates with kinetochores to bring about sister kinetochore co-orientation, an
      essential aspect of meiosis I chromosome segregation. We show here that the Lrs4
      Csm1 complex associates with kinetochores during mitosis. This kinetochore
      localization is observed during anaphase and depends on the on the Mitotic Exit
      Network, a signaling cascade essential for the completion of mitosis.
      Furthermore, we find that Lrs4 and Csm1 are important for chromosome segregation
      fidelity. Our results reveal a previously unanticipated function for Lrs4-Csm1 in
      mitotic chromosome segregation.

PMID- 20818156
TI  - Evidence for a differential modulation of p53-phosphorylating kinases by the
      cyclin-dependent kinase inhibitor p21WAF1/CIP1.
AB  - Although initially described as a regulator of cell cycle progression, the cyclin
      dependent kinase inhibitor p21 is now known to also modulate various other
      biological processes including transcription, differentiation and apoptosis.
      These versatile activities of p21 are mainly mediated via direct binding to
      various transcription factors, pro-apoptotic proteins and kinases that are
      usually inhibited by this interaction. Here we provide in vitro evidence that p21
      not only inhibits, but also activates certain kinases in a remarkable substrate
      dependent manner. Whereas phosphorylation of the tumor suppressor p53 by several
      isoforms of the cJun N-terminal kinases (JNKs) was greatly attenuated in the
      presence of p21, phosphorylation of cJun remained either unaffected or was even
      enhanced. Furthermore, p21 strongly increased phosphorylation of cFos and MBP by
      ERK1 and ERK2, while p53 phosphorylation was increased and inhibited,
      respectively. Also p38alpha and glycogen synthase kinase-3 beta (GSK-3beta) were
      found differentially regulated by p21 in a substrate-dependent manner, while
      casein kinase-1 epsilon (CK1epsilon) was not affected. Together with our finding
      that the stress-induced p53 phosphorylation pattern differs greatly between p21
      proficient and -deficient HCT116 colon carcinoma cells, our results suggest that
      p21 is able to influence kinase activities both in a negative and positive
      manner.

PMID- 20818157
TI  - MASTL is the human orthologue of Greatwall kinase that facilitates mitotic entry,
      anaphase and cytokinesis.
AB  - Greatwall (Gwl) was originally discovered in Drosophila as an essential kinase
      for correct chromosome condensation and mitotic progression. In Xenopus, Gwl may
      influence the positive-feedback loop that directs cyclin B1-Cdk1 activation and
      the mitotic state by inhibiting the phosphatase PP 2A. Here, we describe the
      human orthologue of Gwl called microtubule-associated serine/threonine kinase
      like (MASTL). We found that MASTL localizes to the nucleus in interphase and re
      localizes in part to centrosomes in mitosis, when it is active. Cells strongly
      depleted of MASTL by RNAi delay in G(2) phase and reveal slow chromosome
      condensation. MASTL RNAi cells that enter and progress through mitosis often fail
      to completely separate their sister chromatids in anaphase. This causes chromatin
      to be trapped in the cleavage furrow, which may lead to the formation of 4N G(1)
      cells by cytokinesis failure. Further, our experiments indicate that MASTL
      supports the phosphorylation state of mitotic phospho-proteins downstream of
      cyclin B1-Cdk1, including the APC/C. Cyclin B1 destruction is incomplete when
      mitotic cells that are strongly depleted of MASTL exit mitosis. We propose that
      MASTL enhances cyclin B1-Cdk1-dependent mitotic phosphorylation events, directing
      mitotic entry, anaphase and cytokinesis in human cells.

PMID- 20818158
TI  - IL-6, a risk factor for hepatocellular carcinoma: FLLL32 inhibits IL-6-induced
      STAT3 phosphorylation in human hepatocellular cancer cells.
AB  - Hepatocellular carcinoma (HCC) is one of the most common human cancers and the
      patients' five-year survival rate is very low. Growing evidence indicates that
      interleukin-6 (IL-6) is a risk factor for HCC. High serum IL-6 may promote HCC
      development in hepatitis B patients. Therefore, IL-6 could be considered a HCC
      biomarker and blockade of IL-6 pathway may be a promising therapeutic alternative
      for HCC. STAT3 is major pathway to mediate signal from IL-6 to the nucleus, where
      different genes associated with proliferation and apoptosis are regulated. We
      previous reported that IL-6 induces cell survival upon drug treatment in HCC
      cells and inhibition of IL-6/STAT3 pathway using anti-IL-6 antibody or STAT3
      small-molecule inhibitor LLL12 reduces this effect. Here we summarized the recent
      studies of IL-6 in HCC and showed another STAT3 small-molecule inhibitor FLLL32
      also blocked IL-6-induced STAT3 activation in HCC cells. FLLL32 is a novel
      curcumin analogue, which has been described to suppress the constitutive
      activation of STAT3 in pancreatic and breast cancer cells in vitro and vivo. We
      demonstrated that FLLL32 blocked IL-6-induced STAT3 phosphorylation and nuclear
      translocation.

PMID- 20818160
TI  - Polycomb group genes in stem cell self-renewal: a double-edged sword.
AB  - Polycomb group (PcG) genes encode chromatin associated proteins that usually form
      polycomb repressive complexes (PRC) to maintain the repressive state of gene
      transcription. In both embryonic and adult stem cells, PRCs are commonly regarded
      as essential players for maintaining stem cell multipotency by repressing
      developmental genes. However, emerging evidence also points out essential roles
      of PcG genes in antagonizing stem cell self-renewal and facilitating cell lineage
      differentiation. Here, we briefly review recent literature on these two seemingly
      opposite functions of PcG genes in stem cells and discuss future perspective
      towards understanding polycomb function in stem cells and tumorigenesis.

PMID- 20818161
TI  - Comparison of methyl-DNA immunoprecipitation (MeDIP) and methyl-CpG binding
      domain (MBD) protein capture for genome-wide DNA methylation analysis reveal CpG
      sequence coverage bias.
AB  - DNA methylation primarily occurs at CpG dinucleotides in mammals and is a common
      epigenetic mark that plays a critical role in the regulation of gene expression.
      Profiling DNA methylation patterns across the genome is vital to understand DNA
      methylation changes that occur during development and in disease phenotype. In
      this study, we compared two commonly used approaches to enrich for methylated DNA
      regions of the genome, namely methyl-DNA immunoprecipitation (MeDIP) that is
      based on enrichment with antibodies specific for 5'-methylcytosine (5MeC), and
      capture of methylated DNA using a methyl-CpG binding domain-based (MBD) protein
      to discover differentially methylated regions (DMRs) in cancer. The enriched
      methylated DNA fractions were interrogated on Affymetrix promoter tiling arrays
      and differentially methylated regions were identified. A detailed validation
      study of 42 regions was performed using Sequenom MassCLEAVE technique. This
      detailed analysis revealed that both enrichment techniques are sensitive for
      detecting DMRs and preferentially identified different CpG rich regions of the
      prostate cancer genome, with MeDIP commonly enriching for methylated regions with
      a low CpG density, while MBD capture favors regions of higher CpG density and
      identifies the greatest proportion of CpG islands. This is the first detailed
      validation report comparing different methylated DNA enrichment techniques for
      identifying regions of differential DNA methylation. Our study highlights the
      importance of understanding the nuances of the methods used for DNA genome-wide
      methylation analyses so that accurate interpretation of the biology is not
      overlooked.

PMID- 20818159
TI  - Disparate chromatin landscapes and kinetics of inactivation impact differential
      regulation of p53 target genes.
AB  - The p53 transcription factor regulates the expression of genes involved in
      cellular responses to stress, including cell cycle arrest and apoptosis. The p53
      transcriptional program is extremely malleable, with target gene expression
      varying in a stress- and cell type-specific fashion. The molecular mechanisms
      underlying differential p53 target gene expression remain elusive. Here we
      provide evidence for gene-specific mechanisms affecting expression of three
      important p53 target genes. First we show that transcription of the apoptotic
      gene PUMA is regulated through intragenic chromatin boundaries, as revealed by
      distinct histone modification territories that correlate with binding of the
      insulator factors CTCF, Cohesins and USF1/2. Interestingly, this mode of
      regulation produces an evolutionary conserved long non-coding RNA of unknown
      function. Second, we demonstrate that the kinetics of transcriptional competence
      of the cell cycle arrest gene p21 and the apoptotic gene FAS are markedly
      different in vivo, as predicted by recent biochemical dissection of their core
      promoter elements in vitro. After a pulse of p53 activity in cells, assembly of
      the transcriptional apparatus on p21 is rapidly reversed, while FAS
      transcriptional activation is more sustained. Collectively these data add to a
      growing list of p53-autonomous mechanisms that impact differential regulation of
      p53 target genes.

PMID- 20818162
TI  - Epigenotype switching at the CD14 and CD209 genes during differentiation of human
      monocytes to dendritic cells.
AB  - Using an in vitro model for the differentiation of human blood-derived monocytes
      into dendritic cells (DCs), we have undertaken an investigation of epigenetic
      changes that take place at CD14 and CD209 (DC-SIGN) genes that encode cell
      surface antigens that are crucial for the function of monocytes and DCs,
      respectively. Upon differentiation the cell surface expression of CD14 is lost,
      whilst CD209 expression is increased. These reciprocal changes are associated
      with the loss of epigenetic markers of "activation" at the CD14 locus, but the
      acquisition of the same at the CD209 locus. There is little change in
      "repressive" histone marks and CpG methylation at the CD14 locus. By contrast
      there are changes in both the "repressive" histone marks and CpG methylation at
      the CD209 locus. In particular, two CpG dinucleotides, designated CpG2 and CpG3,
      show a marked demethylation at the CD209 promoter upon differentiation. These
      data provide insight into the epigenetic demands that are necessary to effect the
      reciprocal changes in expression of the CD14 and CD209 genes upon terminal
      differentiation of monocytes into DCs. For repression of the active CD14 gene the
      loss of "activation" histone modifications is likely necessary and sufficient for
      silencing. By contrast the activation of the silent CD209 gene appears to require
      an acquisition of "active" histone modifications and concomitant loss of both
      "repressive" histone marks and CpG methylation.

PMID- 20818163
TI  - A matter of balance between life and death: targeting reactive oxygen species
      (ROS)-induced autophagy for cancer therapy.
AB  - Reactive oxygen species (ROS) have been implicated in many biological functions
      and diseases. Often their role is counterintuitive, where ROS can either promote
      cell survival or cell death depending on the cellular context. Similarly,
      autophagy is involved in many biological functions and diseases where it can
      either promote cell survival or cell death. There is now a growing consensus that
      ROS controls autophagy in multiple contexts and cell types. Furthermore,
      alterations in ROS and autophagy regulation contribute to cancer initiation and
      progression. However, how ROS and autophagy contribute to cancer and how to
      target either for cancer treatment is controversial. Blocking ROS generation
      could prevent cancer initiation, whereas blockage of autophagy seems to be
      required for initiation of cancer. In cancer progression, high levels of ROS
      correspond with increased metabolism and under metabolic stress autophagy is
      required to maintain cellular integrity. In cancer treatment, therapeutic drugs
      that increase ROS and autophagy have been implicated in their mechanism for cell
      death, such as 2-methoxyestrodial (2-ME) and arsenic trioxide (As(2)O(3)),
      whereas other therapeutic drugs that induce ROS and autophagy seem to have a
      protective effect. This has led to different approaches to treat cancer patients
      where autophagy is either activated or inhibited. Both views of ROS and autophagy
      are valid and reflect the balance within a cell to either survive or die.
      Understanding this balancing act within a cell is essential to determine whether
      to block or activate ROS-controlled autophagy for cancer therapy.

PMID- 20818164
TI  - Autophagy-induced regression of hyaloid vessels in early ocular development.
AB  - The hyaloid vessel is a transient intraocular circulatory system that undergoes a
      complete regression as the retina becomes matured with retinal vascularization.
      If the complete involution of the hyaloid vessels fails, the pathological
      persistence of these vessels results in persistent hyperplastic primary vitreous
      (PHPV) associated with severe ocular pathologies. Unfortunately, despite its
      clinical significance, cellular and molecular processes involved in hyaloid
      regression remain to be elucidated. Herein, we for the first time demonstrated
      that autophagy could contribute to the regression of hyaloid vessels in early
      developing retina. In developing retina, hyaloid vessel regression coincided with
      retinal vascular development; this occurred simultaneous with apoptotic and
      autophagic processes. Moreover, in vascular endothelial cells under hypoxic
      conditions, LC3-II conversion was detected along with caspase-3 activation. The
      autophagy inducer rapamycin induced autophagy-mediated cell death of vascular
      endothelial cells in a dose-dependent manner. Moreover, rapamycin significantly
      enhanced the involution of hyaloid vessels in the early developing eye.
      Therefore, our results suggest that the autophagy pathway would be involved in
      hyaloid regression that occurs during early ocular development. Furthermore,
      activation of the autophagy pathway could be considered for a therapeutic
      approach to PHPV.

PMID- 20818165
TI  - Impaired autophagy in Lafora disease.
AB  - Lafora disease (LD) is a progressive, lethal, autosomal recessive,
      neurodegenerative disorder that manifests with myoclonus epilepsy. LD is
      characterized by the presence of intracellular inclusion bodies called Lafora
      bodies (LB), in brain, spinal cord and other tissues. More than 50 percent of LD
      is caused by mutations in EPM2A that encodes laforin. Here we review our recent
      findings that revealed that laforin regulates autophagy. We consider how
      autophagy compromise may predispose to LB formation and neurodegeneration in LD,
      and discuss future investigations suggested by our data.

PMID- 20818166
TI  - Autophagy in pancreatic cancer: an emerging mechanism of cell death.
AB  - Pancreatic cancer, the fourth leading cause of cancer-related death in the United
      States, is resistant to current chemotherapies. Therefore, identification of
      different pathways of cell death is important to develop novel therapeutics. Our
      previous study has shown that triptolide, a diterpene triepoxide, inhibits the
      growth of pancreatic cancer cells in vitro and prevents tumor growth in vivo.
      However, the mechanism by which triptolide kills pancreatic cancer cells was not
      known, hence, this study aimed at elucidating it. Our study reveals that
      triptolide kills diverse types of pancreatic cancer cells by two different
      pathways; it induces caspase-dependent apoptotic death in some cell lines and
      death via a caspase-independent autophagic pathway in the other cell lines
      tested. Triptolide-induced autophagy requires autophagy-specific genes, atg5 or
      beclin 1 and its inhibition results in cell death via the apoptotic pathway,
      whereas inhibition of both autophagy and apoptosis rescues triptolide-mediated
      cell death. Our study shows for the first time that induction of autophagy by
      triptolide has a pro-death role in pancreatic cancer cells. Since triptolide
      kills diverse pancreatic cancer cells by different mechanisms, it makes an
      attractive chemotherapeutic agent for future use against a broad spectrum of
      pancreatic cancers.

PMID- 20818167
TI  - Synthetic substrates for measuring activity of autophagy proteases: autophagins
      (Atg4).
AB  - Atg4 cysteine proteases (autophagins) play crucial roles in autophagy by
      proteolytic activation of Atg8 paralogs for targeting to autophagic vesicles by
      lipid conjugation, as well as in subsequent deconjugation reactions. However, the
      means to measure the activity of autophagins is limited. Herein, we describe two
      novel substrates for autophagins suitable for a diversity of in vitro assays,
      including (i) fluorogenic tetrapeptide acetyl-Gly-L-Thr-L-Phe-Gly-AFC (Ac-GTFG
      AFC) and (ii) a fusion protein comprised of the natural substrate LC3B appended
      to the N-terminus of phospholipase A(2) (LC3B-PLA(2)), which upon cleavage
      releases active PLA(2) for fluorogenic assay. To generate the synthetic
      tetrapeptide substrate, the preferred tetrapeptide sequence recognized by
      autophagin-1/Atg4B was determined using a positional scanning combinatorial
      fluorogenic tetrapeptide library. With the LC3B-PLA(2) substrate, we show that
      mutation of the glycine proximal to the scissile bond in LC3B abolishes activity.
      Both substrates showed high specificity for recombinant purified autophagin
      1/Atg4B compared to closely related proteases and the LC3B-PLA(2) substrate
      afforded substantially higher catalytic rates (k(cat)/K(m) 5.26 x 10(5) M(
      1)/sec(-1)) than Ac-GTFG-AFC peptide (0.92 M(-1)/sec(-1)), consistent with
      substrate-induced activation. Studies of autophagin-1 mutants were also
      performed, including the protease lacking a predicted autoinhibitory domain at
      residues 1 to 24 and lacking a regulatory loop at residues 259 to 262. The
      peptide and fusion protein substrates were also employed for measuring autophagin
      activity in cell lysates, showing a decrease in cells treated with autophagin
      1/Atg4B siRNA or transfected with a plasmid encoding Atg4B (Cys74Ala)
      dominantnegative. Therefore, the synthetic substrates for autophagins reported
      here provide new research tools for studying autophagy.

PMID- 20818168
TI  - A miRNA-tRNA mix-up: tRNA origin of proposed miRNA.
AB  - The rapid release of new data from DNA genome sequencing projects has led to a
      variety of misannotations in public databases. Our results suggest that next
      generation sequencing approaches are particularly prone to such misannotations.
      Two related miRNA candidates did recently enter the miRBase database, miR-1274b
      and miR-1274a, but they share identical 18-nucleotide stretches with tRNA (Lys3)
      and tRNA (Lys5) , respectively. The possibility that the small RNA fragments that
      led to the description of these two miRNAs originated from the two tRNAs was
      examined. The ratio of the miR-1274b:miR-1274a fragments does closely resemble
      the known tRNA lys3:lys5 ratio in the cell. Furthermore, the proposed miRNA
      hairpins have a very low prediction score and the proposed miRNA genes are in
      fact endogenous retroviral elements. We searched for other miRNA-mimics in the
      human genome and found more examples of tRNA-miRNA mimicry. We propose that the
      corresponding miRNAs should be validated in more detail, as the small RNA
      fragments that led to their description are likely derived from tRNA processing.

PMID- 20818169
TI  - Plant homeodomain fingers form a helping hand for transcription.
AB  - Several recent publications demonstrate a co-activator function for a subgroup of
      plant homeodomain fingers, which in humans comprises PHF2, PHF8 and KIAA1718.
      Besides an N-terminal plant homeodomain (PHD) these proteins also harbor an
      enzymatically active Jumonji-C domain (JmjC). While they have been shown to bind
      via their PHDs to H3K4me3-bearing nucleosomes at active gene promoters, their
      JmjC-domains are able to remove mono- and dimethyl-lysine 9 or 27 on histone H3,
      and monomethyl-lysine 20 on histone H4, chromatin modifications which correlate
      with transcriptional repression. Such dual histone crosstalk insures the proper
      removal of repressive histone marks following transcriptional activation by RNA
      polymerases I and II. Mutations in the PHF8 gene lead to X-linked mental
      retardation (XLMR) and knockdown of KIAA1718 and PHF8 homologs in zebrafish
      causes brain defects. Thus, the co-activator function of this new class of
      chromatin modifying enzymes has important functional roles in neuronal
      development. To continue with the nomenclature for histone demethylases, we
      propose the usage of KDM7A, -B and -C for KIAA1718, PHF8 and PHF2 proteins,
      respectively.

PMID- 20818170
TI  - Androgen synthesis and steroid transporters in prostate cancer: rethinking the
      transition to CRPC.

PMID- 20818171
TI  - Myc, Cdk2 and cellular senescence: Old players, new game.
AB  - The aberrant activation of oncogenic pathways promotes tumor progression, but
      concomitantly elicits compensatory tumor-suppressive responses, such as apoptosis
      or senescence. For example, Ras induces senescence, while Myc generally triggers
      apoptosis. Myc is in fact viewed as an anti-senescence oncogene, as it is a
      potent inducer of cell proliferation and immortalization, bypasses growth
      inhibitory signals, and cooperates with Ras in cellular transformation. Recent
      reports prompt re-evaluation of Myc-induced senescence and of its role in tumor
      progression and therapy. We have shown that the cyclin-dependent kinase Cdk2,
      although redundant for cell cycle progression, has a unique role in suppressing a
      Myc-induced senescence program: Myc activation elicited expression of p16(INK4a)
      and p21(Cip1), and caused senescence in cells lacking Cdk2, but not in Cdk2
      proficient cells. We show here that suppression of Myc-induced senescence by Cdk2
      does not occur through phosphorylation of its purported substrate residue in Myc
      (Ser 62). Additional cellular activities have been identified that suppress Myc
      induced senescence, including the Wrn helicase, Telomerase and Miz1. These
      senescencesuppressing activities were critical for tumor progression, as
      deficiency in either Cdk2, telomerase or Miz1 reduced the onset of Myc-induced
      lymphoma in transgenic mice. Other gene products like p53, SUV39H1 or TGFbeta
      promoted senescence, which together with apoptosis contributed to tumor
      suppression. Paradoxically, Myc directly counteracted the very same senescence
      program that it potentially elicited, since it positively regulated Wrn,
      Telomerase and Cdk2 activity. Furthermore, Cdk2 inhibition re-activated the
      latent senescence program in Myc expressing cells. Hence, while these molecules
      are instrumental to the oncogenic action of Myc, they may simultaneously
      constitute its Achille's heel for therapeutic development.

PMID- 20818172
TI  - Calcium signaling during the plant-plant interaction of parasitic Cuscuta reflexa
      with its hosts.
AB  - The plant parasite Cuscuta reflexa induces various responses in compatible and
      incompatible host plants. The visual reactions of both types of host plants
      including obvious morphological changes require the recognition of Cuscuta ssp. A
      consequently initiated signaling cascade is triggered which leads to a tolerance
      of the infection or, in the case of some incompatible host plants, to resistance.
      Calcium (Ca(2+)) release is the major second messenger during signal
      transduction. Therefore, we have studied Ca(2+) spiking in tomato and tobacco
      during infection with C. reflexa. In our recently published study Ca(2+) signals
      were monitored as bioluminescence in aequorin-expressing tomato plants after the
      onset of C. reflexa infestation. Signals at the attachment sites were observed
      from 30 to 48 h after infection. In an assay with leaf disks of aequorin
      expressing tomato which were treated with different C. reflexa plant extracts it
      turned out that the substance that induced Ca(2+) release in the host plant was
      closely linked to the parasite's haustoria.

PMID- 20818173
TI  - Kaposi sarcoma-associated herpesvirus-encoded viral FLICE inhibitory protein
      (vFLIP) K13 cooperates with Myc to promote lymphoma in mice.
AB  - Primary effusion lymphoma (PEL) is an aggressive form of lymphoma that is
      associated with infection by Kaposi's sarcoma-associated herpesvirus (KSHV). One
      of the KSHV genes expressed in PEL cells is K13, a potent activator of the NF
      kappaB pathway. K13 transgenic mice develop lymphomas, but after a long period of
      latency. A possible candidate that could cooperate with K13 in the development of
      PEL is c-Myc, whose expression is frequently dysregulated in PEL cells. To study
      the cooperative interaction between K13 and c-Myc in the pathogenesis of PEL, we
      crossed the K13 transgenic mice to iMyc(EMU) transgenic mice that overexpress
      Myc. We report that lymphomas in the K13/iMyc(EMU) double transgenic mice
      developed with shorter latency and were histologically distinct from those
      observed in the iMyc(EMU) mice. Lymphomas in the K13/iMyc(EMU) mice also lacked
      the expression of B- and T-cell markers, thus resembling the immunophenotype of
      PEL. The accelerated development of lymphoma in the K13/iMyc(EMU) mice was
      associated with increased expression of K13, elevated NF-kappaB activity and
      decrease in apoptosis. Taken collectively, our results demonstrate a cooperative
      interaction between the NF-kappaB and Myc pathways in lymphomagenesis.

PMID- 20818174
TI  - Ketones and lactate "fuel" tumor growth and metastasis: Evidence that epithelial
      cancer cells use oxidative mitochondrial metabolism.
AB  - Previously, we proposed a new model for understanding the "Warburg effect" in
      tumor metabolism. In this scheme, cancer-associated fibroblasts undergo aerobic
      glycolysis and the resulting energy-rich metabolites are then transferred to
      epithelial cancer cells, where they enter the TCA cycle, resulting in high ATP
      production via oxidative phosphorylation. We have termed this new paradigm "The
      Reverse Warburg Effect." Here, we directly evaluate whether the end-products of
      aerobic glycolysis (3-hydroxy-butyrate and L-lactate) can stimulate tumor growth
      and metastasis, using MDA-MB-231 breast cancer xenografts as a model system. More
      specifically, we show that administration of 3-hydroxy-butyrate (a ketone body)
      increases tumor growth by ~2.5-fold, without any measurable increases in tumor
      vascularization/angiogenesis. Both 3-hydroxy-butyrate and L-lactate functioned as
      chemo-attractants, stimulating the migration of epithelial cancer cells. Although
      L-lactate did not increase primary tumor growth, it stimulated the formation of
      lung metastases by ~10-fold. Thus, we conclude that ketones and lactate fuel
      tumor growth and metastasis, providing functional evidence to support the
      "Reverse Warburg Effect". Moreover, we discuss the possibility that it may be
      unwise to use lactate-containing i.v. solutions (such as Lactated Ringer's or
      Hartmann's solution) in cancer patients, given the dramatic metastasis-promoting
      properties of L-lactate. Also, we provide evidence for the up-regulation of
      oxidative mitochondrial metabolism and the TCA cycle in human breast cancer cells
      in vivo, via an informatics analysis of the existing raw transcriptional profiles
      of epithelial breast cancer cells and adjacent stromal cells. Lastly, our
      findings may explain why diabetic patients have an increased incidence of cancer,
      due to increased ketone production, and a tendency towards autophagy/mitophagy in
      their adipose tissue.

PMID- 20818175
TI  - The Axl receptor tyrosine kinase is an adverse prognostic factor and a
      therapeutic target in esophageal adenocarcinoma.
AB  - Esophageal adenocarcinoma (EAC) arises in the backdrop of reflux-induced
      metaplastic phenomenon known as Barrett esophagus. The prognosis of advanced EAC
      is dismal, and there is an urgent need for identifying molecular targets for
      therapy. Serial Analysis of Gene Expression (SAGE) was performed on metachronous
      mucosal biopsies from a patient who underwent progression to EAC during
      endoscopic surveillance. SAGE confirmed significant upregulation of Axl "tags"
      during the multistep progression of Barrett esophagus to EAC. In a cohort of 92
      surgically resected EACs, Axl overexpression was associated with shortened median
      survival on both univariate (p < 0.004) and multivariate (p < 0.036) analysis.
      Genetic knockdown of Axl receptor tyrosine kinase (RTK) function was enabled in
      two EAC lines (OE33 and JH-EsoAd1) using lentiviral short hairpin RNA (shRNA).
      Genetic knockdown of Axl in EAC cell lines inhibited invasion, migration, and in
      vivo engraftment, which was accompanied by downregulation in the activity of the
      Ral GTPase proteins (RalA and RalB). Restoration of Ral activation rescued the
      transformed phenotype of EAC cell lines, suggesting a novel effector mechanism
      for Axl in cancer cells. Pharmacological inhibition of Axl was enabled using a
      small molecule antagonist, R428 (Rigel Pharmaceuticals). Pharmacological
      inhibition of Axl with R428 in EAC cell lines significantly reduced anchorage
      independent growth, invasion and migration. Blockade of Axl function abrogated
      phosphorylation of ERBB2 (Her-2/neu) at the Tyr877 residue, indicative of
      receptor crosstalk. Axl RTK is an adverse prognostic factor in EAC. The
      availability of small molecule inhibitors of Axl function provides a tractable
      strategy for molecular therapy of established EAC.

PMID- 20818177
TI  - The use of wideband filters in distinguish green fluorescent protein in roots of
      arbuscular mycorrhizal symbiosis.
AB  - Arbuscular mycorrhizal (AM) fungi form arbuscules in the inner cortical cells of
      roots. Accumulation of autofluorescent materials within the roots, especially
      around senescent arbuscules, has hampered analyses of the localization and
      dynamics of green fluorescent protein (GFP)-fusion proteins in arbusculated
      cells. In this report, the author proposes an efficient method to distinguish GFP
      from autofluorescence. To detect GFP fluorescence, colonized cells were observed
      with wideband filters rather than GFP-specialized filters because the
      autofluorescence generally has a broad fluorescent spectrum that can easily be
      distinguished from GFP by color. Moreover, the autofluorescence of arbusculated
      cells could possibly contain strong green fluorescence that could not be excluded
      by GFP-specialized filters. The multicolor imaging and in vivo real-time
      observations suggested that the expression of autofluorescence in arbusculated
      cells did not overlap with the expression of OsPT11-GFP, a useful marker for
      active arbuscules, and that autofluorescent materials appeared after the
      initiation of senescence in infection units.

PMID- 20818178
TI  - Autophagy gets a brake: DAP1, a novel mTOR substrate, is activated to suppress
      the autophagic process.
AB  - Autophagy, a highly regulated catabolic process, is controlled by the action of
      positive and negative regulators. While many of the positive mediators of
      autophagy have been identified, very little is known about negative regulators
      that might counterbalance the process. We recently identified deathassociated
      protein 1 (DAP1) as a suppressor of autophagy and as a novel direct substrate of
      mammalian target of rapamycin (mTOR). We found that DAP1 is functionally silent
      in cells growing under rich nutrient supplies through mTOR-dependent inhibitory
      phosphorylation on two sites, which were mapped to Ser3 and Ser51. During amino
      acid starvation, mTOR activity is turned off resulting in a rapid reduction in
      the phosphorylation of DAP1. This caused the conversion of the protein into a
      suppressor of autophagy, thus providing a buffering mechanism that
      counterbalances the autophagic flux and prevents its overactivation under
      conditions of nutrient deprivation. Based on these studies we propose the "gas
      and brake" concept in which mTOR, the main sensor that regulates autophagy in
      response to amino acid deprivation, also controls the activity of a specific
      balancing brake to prevent the overactivation of autophagy.

PMID- 20818176
TI  - Charge variants in IgG1: Isolation, characterization, in vitro binding properties
      and pharmacokinetics in rats.
AB  - Antibody charge variants have gained considerable attention in the biotechnology
      industry due to their potential influence on stability and biological activity.
      Subtle differences in the relative proportions of charge variants are often
      observed during routine biomanufacture or process changes and pose a challenge to
      demonstrating product comparability. To gain further insights into the impact on
      biological activity and pharmacokinetics (PK) of monoclonal antibody (mAb) charge
      heterogeneity, we isolated the major charge forms of a recombinant humanized IgG1
      and compared their in vitro properties and in vivo PK. The mAb starting material
      had a pI range of 8.7-9.1 and was composed of about 20% acidic variants, 12%
      basic variants, and 68% main peak. Cation exchange displacement chromatography
      was used to isolate the acidic, basic, and main peak fractions for animal
      studies. Detailed analyses were performed on the isolated fractions to identify
      specific chemical modification contributing to the charge differences, and were
      also characterized for purity and in vitro potency prior to being administered
      either subcutaneously (SC) or intravenously (IV) in rats. All isolated materials
      had similar potency and rat FcRn binding relative to the starting material.
      Following IV or SC administration (10 mg/kg) in rats, no difference in serum PK
      was observed, indicating that physiochemical modifications and pI differences
      among charge variants were not sufficient to result in PK changes. Thus, these
      results provided meaningful information for the comparative evaluation of charge
      related heterogeneity of mAbs, and suggested that charge variants of IgGs do not
      affect the in vitro potency, FcRn binding affinity, or the PK properties in rats.

PMID- 20818179
TI  - Dynamic compositional changes of detergent-resistant plasma membrane microdomains
      during plant cold acclimation.
AB  - Plants increase their freezing tolerance upon exposure to low, non-freezing
      temperatures, which is known as cold acclimation. Cold acclimation results in a
      decrease in the proportion of sphingolipids in the plasma membrane in many plants
      including Arabidopsis thaliana. The decrease in sphingolipids has been considered
      to contribute to the increase in the cryostability of the plasma membrane through
      regulating membrane fluidity. Recently we have proposed a possibility of another
      important sphingolipid function associated with cold acclimation. In animal
      cells, it has been known that the plasma membrane contains microdomains due to
      the chanracteristics of sphingolipids and sterols, and the sphingolipid- and
      sterol-enriched microdomains are thought to function as platforms for cell
      signaling, membrane trafficking and pathogen response. In our research on
      characterization of microdomain-associated lipids and proteins in Arabidopsis,
      cold-acclimation-induced decrease in sphingolipids resulted in a decrease of
      microdomains in the plasma membrane and there were considerable changes in
      membrane transport-, cytoskeleton- and endocytosis-related proteins in the
      microdomains during cold acclimation. Based on these results, we discuss a
      functional relationship between the changes in microdomain components and plant
      cold acclimation.

PMID- 20818180
TI  - DAY NEUTRAL FLOWERING does not act through GIGANTEA and FKF1 to regulate CONSTANS
      expression and flowering time.
AB  - The regulation of CONSTANS (CO) gene expression and protein levels is the
      critical factor in determining a plant's response to photoperiod, flowering is
      induced when high levels of CO protein are present in the light. The regulation
      of CO transcription is mediated in part by GIGANTEA (GI), FKF1 and the CYCLING
      DOF FACTORS (CDFs) and factors affecting the levels of these proteins will also
      affect CO expression. The DAY NEUTRAL FLOWERING (DNF) protein is an E3 ligase
      involved in repressing CO expression in the early part of the day. In this
      article we present evidence to support the argument that DNF is not acting
      through the GI/FKF1/CDF regulatory mechanism to repress CO expression, but that
      it acts on another transcriptional activator of CO.

PMID- 20818181
TI  - Evolutionary coupling in the K(V)1.2-beta2 complex.
AB  - K(V)1.2 is a potassium channel protein whose electrophysiological properties,
      including an oxygen sensing response, are modulated by auxiliary beta subunits.
      The beta subunits are homologous to oxidoreductases, supporting a hypothesis that
      the coupling of the two subunits helps connect the redox state of the cell to the
      electrical activity of the membrane. However the exact mechanism of the coupling
      has not been discovered to-date. We apply evolutionary correlation analysis to
      infer previously unknown components of the interaction network regulating the
      response to hypoxia of the K(V)1.2/beta2 complex. Briefly, evolutionary
      correlation analysis involves finding correlated amino acid substitutions in
      functionally equivalent proteins (for both subunits) across a range of species.
      The method thus depends on a reliable method of inferring functionally equivalent
      (orthologous) proteins in different species, which method we describe in a paper
      recently published in PLoS ONE. One key finding is the characterization of a
      network of motif interactions between the alpha and the beta subunits. By
      significance testing, we show that the likelihood of the correlations shown in
      the K(V)1.2-beta two interaction motifs arising by chance is less than 0.0003,
      which shows that the correlations are statistically highly significant. We
      therefore believe that the correlations are likely to be biologically relevant.
      Other major findings are correlations between specific motifs in the K(V)1.2
      beta2 complex and motifs in other proteins such as RACK1 and Eif36sip, which in
      turn are connected to the hypoxia response. Our paper combines this correlation
      with the literature evidence on potassium channel inactivation and hypoxia
      response to identify specific motifs to serve as experimental targets for studies
      focused on this response. This work aims to add to our general understanding of
      two major issues in ion channel science: 1) how multi-protein complexes including
      ion channels function in coordinated fashion, and 2) how ion channels mediate the
      conversation between the intracellular and extracellular environments. We also
      aim to apply to ion channel science the principle that domain-domain interactions
      in proteins can be inferred from correlation of amino-acid substitutions in sets
      of functionally equivalent proteins.

PMID- 20818182
TI  - Actinomycin D synergistically enhances the efficacy of the BH3 mimetic ABT-737 by
      downregulating Mcl-1 expression.
AB  - Many types of cancer cells possess the ability to evade apoptosis, leading to
      their rapid and uncontrolled proliferation. As major regulators of apoptosis, Bcl
      2 proteins serve as emerging targets for novel chemotherapeutic strategies. In
      this study, we examined the involvement of Bcl-2 proteins in apoptosis induced by
      the chemotherapeutic agent actinomycin D. A dramatic decrease in anti-apoptotic
      myeloid leukemia cell differentiation protein (Mcl-1) mRNA and protein expression
      was detected upon actinomycin D treatment. Further, Mcl-l over-expression caused
      resistance to cell death upon treatment with actinomycin D, implicating a role
      for the down-regulation of Mcl-1 in actinomycin D-induced apoptosis. We also
      explored the therapeutic potential of actinomycin D in combination with ABT-737,
      an experimental agent that inhibits anti-apoptotic Bcl-2 proteins. Actinomycin D
      sensitized cells to ABT-737 treatment in a Bak- or Bax-dependent manner.
      Importantly, low concentrations of actinomycin D and ABT-737 were more effective
      in inducing cell death in transformed cells than their untransformed
      counterparts. A synergistic effect of actinomycin D and ABT-737 on cell death was
      observed in several human tumor cell lines. Like actinomycin D treatment,
      knocking down Mcl-1 expression greatly sensitized tumor cells to ABT-737, and Mcl
      1 over-expression abrogated the cytotoxic effect induced by ABT-737 and
      actinomycin D. These results suggest that the down-regulation of Mcl-1 by
      actinomycin D is likely responsible for the observed synergistic effect between
      the two drugs. Overall, our studies provide compelling evidence that the
      combination of actinomycin D and ABT-737 may lead to an effective cancer
      treatment strategy.

PMID- 20818183
TI  - The role of an E-box element: multiple frunctions and interacting partners.
AB  - Circadian clocks can be entrained by light-dark or temperature cycles. In the
      green alga Chlamydomonas reinhardtii, 12h changes in temperature between 18
      degrees C and 28 degrees C synchronize its clock. Both subunits of the circadian
      RNA-binding protein CHLAMY1, named C1 and C3, are able to integrate temperature
      information. C1 gets hyper-phosphorylated in cells grown at 18 degrees C and the
      level of C3 is up-regulated at this temperature. In the long period mutant per1,
      where temperature entrainment is disturbed, the temperature-dependent regulation
      of C1 and C3 is altered. Up-regulation of C3 at the low temperature is mediated
      predominantly by an E-box element situated in its promoter region. This cis
      acting element is also relevant for circadian expression of c3 as well as of its
      up-regulation in cells, where C1 is overexpressed. Among the few identified
      factors interacting with the E-box region, C3 is also present, suggesting that it
      feedbacks on its own transcription.

PMID- 20818184
TI  - The N-terminal domain of Orai3 determines selectivity for activation of the store
      independent ARC channel by arachidonic acid.
AB  - Although highly selective Ca2(+) entry pathways play a critical role in agonist
      activated Ca2(+) signals in non-excitable cells, only with the recent discovery
      of the Orai proteins have the first insights into the molecular nature of these
      pathways been possible. To date, just two such highly Ca2(+)-selective "Orai
      channels" have been identified in native cells - the store-operated CRAC channels
      and the store-independent, arachidonic acid-activated ARC channels. Studies have
      shown that the functional CRAC channel pore is formed by a tetrameric arrangement
      of Orai1 subunits, whilst a heteropentamer of three Orai1 subunits and two Orai3
      subunits forms the functional ARC channel pore. Importantly, this inclusion of
      Orai3 subunits in the ARC channel structure has been shown to play a specific
      role in determining the selectivity of these channels for activation by
      arachidonic acid. Using an approach based on the expression of various
      concatenated constructs, we examined the basis for this Orai3-dependent effect on
      selectivity for arachidonic acid. We show that, whilst heteropentamers containing
      only one Orai3 subunit are sensitive to arachidonic acid, specific selectivity
      for activation by this fatty acid is only achieved on inclusion of the second
      Orai3 subunit in the pentamer. Further studies identified the cytosolic N
      terminal domain of Orai3 as the region specifically responsible for this switch
      in selectivity. Substitution of just this domain into an otherwise complete
      single Orai1 subunit within a concatenated 31111 pentamer is sufficient to change
      the resulting channel from one that is predominantly store-operated, to one that
      is exclusively activated by arachidonic acid.

PMID- 20818185
TI  - Beclin 1-independent autophagy induced by a Bcl-XL/Bcl-2 targeting compound, Z18.
AB  - Inhibitors of Bcl-XL/Bcl-2 can induce autophagy by releasing the autophagic
      protein Beclin 1 from its complexes with these proteins. Here we report a novel
      compound targeting the BH3 binding groove of Bcl-XL/Bcl-2, Z18, which efficiently
      induces autophagy-associated cell death in HeLa cells, without apparent
      apoptosis. Unexpectedly, the inhibition of Beclin 1 and phosphatidylinositol 3
      kinase have no obvious effect on Z18-induced autophagy in HeLa cells, implying
      that it is a non-canonical Beclin 1-independent autophagy. Meanwhile, the
      accumulation of autophagosomes is positively correlated with Z18-induced cell
      death and the full flux of autophagy is not necessary.

PMID- 20818186
TI  - A fusion protein with the receptor-binding domain of vascular endothelial growth
      factor-A (VEGF-A) is an antagonist of angiogenesis in cancer treatment:
      Simultaneous blocking of VEGF receptor-1 and 2.
AB  - Vascular endothelial growth factor (VEGF) is an angiogenic factor that signals
      through VEGFR-1 and VEGFR-2, which are expressed preferentially in proliferating
      endothelial cells. Thus, simultaneous blockage of both VEGF receptors may provide
      a more efficient therapeutic response in cancer treatment. We created a
      recombinant fusion protein (RBDV-IgG1 Fc), which is composed of the receptor
      binding domain of human VEGF-A (residues 8-109) and the Fc region of human IgG1
      immunoglobulin. The recombinant protein can bind to both mouse VEGFR-1 and VEGFR
      2 to decrease VEGF-induced proliferation and tube formation of endothelial cells
      in vitro. In this study, the RBDV-IgG1 Fc fusion protein reduced the effects of
      proliferation, migration and tube formation induced by VEGF in murine endothelial
      cells in vitro. In vivo tumor therapy with RBDV-IgG1 Fc resulted in tumor
      inhibition by reducing angiogenesis. Pathological evidence also shows that RBDV
      IgG1 Fc can seriously damage vessels, causing the death of tumor cells. These
      findings suggest that this chimeric protein has potential as an angiogenesis
      antagonist in tumor therapy.

PMID- 20818187
TI  - The sociology of return-to-play decision making: a clinical perspective.

PMID- 20818188
TI  - Overuse injury of the physis: a "growing" problem.

PMID- 20818189
TI  - Researchers in sports medicine are key players in the field of preventive health
      care.

PMID- 20818190
TI  - Arthroscopic meniscal transplants in soccer players: outcomes at 2- to 5-year
      follow-up.
AB  - OBJECTIVE: To assess the midterm effects of meniscal transplants on clinical and
      functional knee scores and on the return to sports rate in soccer players.
      DESIGN: Retrospective case series. SETTING: Department of Orthopaedic Surgery,
      Clinica del Pilar, Barcelona, Spain. PATIENTS: Fifty-nine meniscal transplants in
      57 patients between 2001 and 2006 were reviewed. Only soccer players with a
      history of meniscectomy and no other ipsilateral knee surgeries before or after
      the meniscal transplant were included in the study. Fifteen patients met
      inclusion criteria. INTERVENTION: Main outcomes were obtained from the sample
      after meniscal transplant and compared with preoperative data, with a mean follow
      up of 36 months. A subgroup analysis was performed considering the degree of
      chondral lesion (no lesions, grade I-II, and grade III-IV). MAIN OUTCOME
      MEASURES: Scores on Lysholm, Subjective International Knee Documentation
      Committee (IKDC) form, and visual analog scale (VAS) scale for pain and
      information regarding return to play. RESULTS: One of the 15 patients had a graft
      failure (6.6%) after a daily life accident. Twelve of the 14 patients included in
      the analysis (85.7%) returned to play soccer. Patients demonstrated significant
      improvements for Lysholm (P = 0.006), Subjective IKDC Form (P = 0.001), and VAS
      for pain (P < 0.0001) scores after the meniscal transplant. Depending on the
      degree of chondral lesion (subgroup analysis), there were no significant
      interactions for Lysholm, Subjective IKDC Form, and VAS for pain scores.
      CONCLUSIONS: Arthroscopic meniscal transplants improve knee symptoms and knee
      function and allow return to play in soccer players, regardless of the degree of
      chondral lesion.

PMID- 20818191
TI  - Can footwear affect achilles tendon loading?
AB  - OBJECTIVE: To investigate the effects of footwear on Achilles tendon tension by
      directly measuring Achilles tendon tension and dorsiflexion range of motion.
      DESIGN: A total of 48 matched pair tests were performed comparing the effects of
      shoe type (high-top vs low-top) for each shoelace configuration (tied vs untied).
      These were performed using the Achilles tendons of 4 human cadaver lower
      extremities that were instrumented with a customized load cell designed to
      measure tension. The lower extremity was inverted in a custom testing apparatus
      designed to inertially invoke dorsiflexion of the foot, putting the Achilles
      tendon in tension. SETTING: Research laboratory. PATIENTS: Left and right lower
      extremities of 2 human cadavers. INTERVENTIONS: None. Independent variables were
      shoe type and shoelace configuration. MAIN OUTCOME MEASURES: Achilles tendon
      tension and dorsiflexion range of motion. RESULTS: High-top shoes significantly
      reduced peak Achilles tendon tension by an average of 9.9% when compared with low
      top shoes. Tied laces significantly reduced peak tension for low-top (3.7%) and
      high-top (12.8%) shoes when compared with untied laces. With tied laces, high-top
      shoes significantly reduced peak dorsiflexion angle by an average of 7.2% when
      compared with low-top shoes. Tied laces with high-top shoes significantly reduced
      peak dorsiflexion angle by an average of 4.7% when compared with untied laces. A
      P value of 0.05 was determined to be significant. CONCLUSIONS: This study offers
      valuable insight that footwear can affect Achilles tendon loading during
      dorsiflexion.

PMID- 20818192
TI  - Statistical performance in National Football League athletes after lumbar
      discectomy.
AB  - OBJECTIVE: It is currently unknown how a lumbar disk herniation (LDH) impacts a
      professional athlete's performance and/or career. No studies have evaluated the
      effects of LDH on National Football League (NFL) skill position players. Our
      objective was to determine if NFL athletes who sustain an LDH and subsequently
      undergo discectomy can return to competitive play with no significant effects on
      performance. DESIGN: Retrospective cohort study. SETTING: National Football
      League. PATIENTS: During a 22-year period (1986-2008), offensive skill position
      players in the NFL (quarterbacks, running backs, wide receivers, and tight ends)
      who sustained an LDH and subsequently underwent a lumbar discectomy were included
      in this study. INTERVENTION: Lumbar discectomy. MAIN OUTCOME MEASURES:
      Performance-based outcomes were analyzed, and data were recorded for games
      played, yards gained, and touchdowns scored. RESULTS: : Data were analyzed for 23
      NFL offensive skill position players who had an LDH and underwent discectomy.
      Seventy-four percent of players returned to competitive play in the NFL. The
      average length of career after treatment was 36 games over a 4.1-year period.
      There was no significant difference in performance when comparing pre-injury and
      post-injury statistics. CONCLUSIONS: Although an LDH has career-threatening
      implications for NFL athletes, 74% of players who underwent lumbar discectomy
      returned to competitive play in the NFL. There was no significant change in
      performance when comparing pre-injury and post-injury statistics.

PMID- 20818193
TI  - Effects of nordic walking and exercise in type 2 diabetes mellitus: a randomized
      controlled trial.
AB  - OBJECTIVE: Both Nordic walking and Exercise on Prescription have potential as
      elements in the management of type 2 diabetes mellitus. These programs are
      recommended, but their effectiveness has not yet been established. The aim was to
      evaluate the efficacy of these 2 interventions compared with standard information
      on physical activity. DESIGN: Single-blinded, randomized, controlled intervention
      study. SETTING: Sixty-eight patients (37 men and 31 women) were randomized into 3
      groups: Nordic walking (NW; n = 22), Exercise on Prescription (EP; n = 24), and
      control (CG; n = 22). PATIENTS: : Patients were recruited from a diabetes
      outpatient clinic and via newspaper advertisement. INTERVENTIONS: Consisted of a
      4-month intervention period followed by an 8-month follow-up, during which the
      participants were recommended to train on their own. MAIN OUTCOME MEASURES: :
      HbA1c. RESULTS: : There was no difference in HbA1c when comparing the
      intervention groups relative to the control group: DeltaNW = -0.4% [95%
      confidence intervals (CI), -0.9% to 0.1%] and DeltaEP = -0.2% (95% CI, -0.6% to
      0.2%) after 4 months; DeltaNW = 0.0% (95% CI, -0.6% to 0.5%) and DeltaEP = 0.3%
      (95% CI, -0.3% to 0.9%) after 12 months. However, fat mass assessed by dual
      energy X-ray absorptiometry (DXA) decreased significantly in the NW group after 4
      months [-1.0 kg (95% CI, -1.7 to 0.1)] and after 12 months in both NW [-1.8 kg
      (95% CI, -3.2 to -0.4)] and EP [-1.5 kg (95% CI, -2.9 to -0.05)] groups. No
      significant changes in other variables. CONCLUSIONS: Four-month exercise programs
      at moderate intensity of either Nordic walking or Exercise on Prescription did
      not significantly improve HbA1c in patients with type 2 diabetes either at the
      end of the program or at the follow-up.

PMID- 20818194
TI  - The effectiveness of compression garments and lower limb exercise on post
      exercise blood pressure regulation in orthostatically intolerant athletes.
AB  - OBJECTIVE: Orthostatic intolerance (OI) may occur postexercise in normotensive
      individuals due to gravitational stress and removal of muscle pump. DESIGN: Six
      subjects performed 3 maximal bouts of exercise associated with (1) no
      intervention (CONTROL) (initial trial), (2) with use of lower limb compression
      garment (TROU), and (3) lower limb exercise (HEEL). SETTING: In each trial, 10
      minutes of supine rest was followed by 10 minutes of standing before and
      immediately after maximal exercise. PARTICIPANTS: All subjects were OI during the
      CONTROL trial. INTERVENTIONS: In the TROU trial, the compression garment was worn
      during the supine and standing phases. In the HEEL trial, heel raises were
      performed every 60 seconds during standing periods. MAIN OUTCOME MEASURES:
      Systolic blood pressure and heart rate were continuously recorded, and stroke,
      cardiac output, and total peripheral resistance were estimated (PortAPres, TNO
      Biomedical Instrumentation, Amsterdam, the Netherlands). Positional changes were
      compared preexercise and postexercise in CONTROL, TROU, and HEEL via 2-way
      analysis of variance. RESULTS: All 6 subjects experienced OI in the CONTROL
      trial, but this was reduced to 2 after the HEEL and 1 after the TROU. Minor
      increases in systolic blood pressure (CONTROL, 3 +/- 11; TROU, 12 +/- 18; HEEL, 7
      +/- 15 mm Hg) and heart rate (CONTROL, 10 +/- 12; TROU, 16 +/- 8; HEEL, 15 +/- 13
      beats.min) were observed, but total peripheral resistance did not alter
      significantly during orthostasis postexercise (CONTROL, 0.462 +/- 0.351; TROU,
      0.325 +/- 0.212; HEEL, 0.746 +/- 0.412 medical units). CONCLUSIONS: It seems that
      simple methods/practices adopted by athletes can have a positive impact on OI.

PMID- 20818195
TI  - High prevalence of vitamin D insufficiency in athletes and dancers.
AB  - OBJECTIVE: Vitamin D insufficiency is prevalent in various populations worldwide
      but with scarce data on physically active individuals. Vitamin D is important to
      athletes, affecting bone mass, immunity, and physical performance. This study
      evaluated the prevalence of vitamin D insufficiency and deficiency among young
      athletes and dancers. DESIGN: Cross-sectional study. SETTING: : Sport medicine
      clinic. PATIENTS: Data on 98 athletes and dancers (age, 14.7 +/- 3.0 years;
      range, 10-30 years; 53% men), who had undergone screening medical evaluations,
      were extracted from medical records. INDEPENDENT VARIABLE: Serum 25(OH)D
      concentrations. MAIN OUTCOME MEASURES: Serum 25(OH)D concentrations, age, sex,
      sport discipline, month of blood test, and serum ferritin. Vitamin D
      insufficiency was defined as serum 25(OH)D concentration <30 ng/mL. RESULTS: Mean
      serum 25(OH)D concentration was 25.3 +/- 8.3 ng/mL. Seventy-three percent of
      participants were vitamin D insufficient. Prevalence of vitamin D insufficiency
      was higher among dancers (94%), basketball players (94%), and Tae Kwon Do
      fighters (67%) and among athletes from indoor versus outdoor sports (80% vs 48%;
      P = 0.002). 25(OH)D levels adjusted for age and sex correlated with serum
      ferritin and season. CONCLUSIONS: In this study, conducted among young athletes
      and dancers from various disciplines in a sunny country, a high prevalence of
      vitamin D insufficiency was identified. A higher rate of vitamin D insufficiency
      was found among participants who practice indoors, during the winter months, and
      in the presence of iron depletion. Given the importance of vitamin D to athletes
      for several reasons, we suggest that athletes and dancers be screened for vitamin
      D insufficiency and treated as needed.

PMID- 20818196
TI  - Vascular conductance is reduced after menthol or cold application.
AB  - OBJECTIVE: To compare the effects of commercially sold menthol (3.5%) ointment
      and cold application on blood flow in the forearm. DESIGN: : Prospective
      counterbalanced design. SETTING: University research laboratory. PARTICIPANTS:
      Twelve (6 men and 6 women) college-aged students. INTERVENTIONS: Each participant
      had blood flow measured in the brachial artery for 5 minutes before and 10
      minutes after menthol ointment or cold application to the forearm. MAIN OUTCOME
      MEASURES: Blood velocity, arterial diameter size, and blood pressure were
      recorded during testing procedures. Vascular conductance was calculated based on
      these measures and used to describe limb blood flow. RESULTS: We observed a
      significant reduction (35%; P = 0.004) in vascular conductance within 60 seconds
      of menthol and cold application to the forearm. Vascular conductance remained
      significantly reduced for 10 minutes by approximately 19% after both menthol and
      cold application [F(2.313, 43.594) = 10.328, P < 0.0001]. There was no
      significant difference between conditions [F(1, 19) = 0.000, P = 0.945].
      CONCLUSIONS: The application of a 3.5% menthol ointment significantly reduces
      conductance in the brachial artery within 60 seconds of application, and this
      effect is maintained for at least 10 minutes after application. The overall
      decline in conductance is similar between menthol ointment and cold application.

PMID- 20818197
TI  - Implementing an electronic point-of-care medical record at an organized athletic
      event: challenges, pitfalls, and lessons learned.
AB  - OBJECTIVE: We examined the feasibility of implementing an electronic health
      record (EHR) at an international running event. DESIGN: Institutional review
      board-approved observational study. SETTING: An annual international running
      event supported by an on-site medical facility. PARTICIPANTS: All registered
      athletes. INTERVENTION: Web-based EHR provided at no cost. Participants were
      asked to populate it with essential health data. The EHR was accessed for runners
      requiring medical services. MAIN OUTCOME MEASURES: Obstacles to EHR utilization,
      reliability of EHR functionality in the field, and ability to correctly match
      runners to their EHR. RESULTS: Only 320 (5%) of the participants utilized the
      EHR. Repeated notification, no cost, and ready access proved to be insufficient
      drivers for use. Lack of reliable Internet connectivity hampered full
      functionality. "Bib swapping" may pose a risk for participant misidentification
      with resultant electronic medical error. CONCLUSIONS: Barriers to the successful
      utilization of an EHR were identified. Despite education and promotion, voluntary
      participant enrollment was a challenge. Mandatory enrollment will be required if
      universal EHR adoption is the goal. Internet connectivity needs to be
      logistically planned. Future efforts should focus on measures to ensure that EHRs
      are correctly matched to participants. Bib swapping must be eliminated if
      athletes are to be identified by their assigned numbers.

PMID- 20818198
TI  - Return-to-play in sport: a decision-based model.
AB  - OBJECTIVE: Return-to-play (RTP) decisions are fundamental to the practice of
      sports medicine but vary greatly for the same medical condition and circumstance.
      Although there are published articles that identify individual components that go
      into these decisions, there exists neither quantitative criteria nor a model for
      the sequence or weighting of these components within the medical decision-making
      process. Our objective was to develop a decision-based model for clinical use by
      sports medicine practitioners. DATA SOURCES: English literature related to RTP
      decision making. MAIN RESULTS: We developed a 3-step decision-based RTP model for
      an injury or illness that is specific to the individual practitioner making the
      RTP decision: health status, participation risk, and decision modification. In
      Step 1, the Health Status of the athlete is assessed through the evaluation of
      Medical Factors related to how much healing has occurred. In Step 2, the
      clinician evaluates the Participation Risk associated with participation, which
      is informed by not only the current health status but also by the Sport Risk
      Modifiers (eg, ability to protect the injury with padding, athlete position).
      Different individuals are expected to have different thresholds for "acceptable
      level of risk," and these thresholds will change based on context. In Step 3,
      Decision Modifiers are considered and the decision to RTP or not is made.
      CONCLUSIONS: Our model helps clarify the processes that clinicians use
      consciously and subconsciously when making RTP decisions. Providing such a
      structure should decrease controversy, assist physicians, and identify important
      gaps in practice areas where research evidence is lacking.

PMID- 20818199
TI  - The practical management of swimmer's painful shoulder: etiology, diagnosis, and
      treatment.
AB  - Shoulder pain is the most common musculoskeletal complaint in competitive
      swimmers. Problems with the shoulders of swimmers resemble that of the disabled
      thrower's shoulder, but the clinical findings and associated dysfunctions are not
      quite the same. Therefore, swimmers with shoulder pain should be evaluated and
      treated as a separate clinical entity, aimed toward underlying pathology and
      dysfunction. Balanced strength training of the rotator cuff, improvement of core
      stability, and correction of scapular dysfunction is central in treatment and
      prevention. Technical and training mistakes are still a major cause of shoulder
      pain, and intervention studies that focus on this are desirable. Imaging
      modalities rarely help clarify the diagnosis, their main role being exclusion of
      other pathology. If nonoperative treatment fails, an arthroscopy with
      debridement, repair, or reduction of capsular hyperlaxity is indicated. The
      return rate and performance after surgery is low, except in cases where minor
      glenohumeral instability is predominant. Overall, the evidence for clinical
      presentation and management of swimmer's shoulder pain is sparse. Preliminary
      results of an intervention study show that scapular dyskinesis can be prevented
      in some swimmers. This may lead to a reduction of swimmer's shoulder problems in
      the future.

PMID- 20818200
TI  - Subretinal hemorrhage in a soccer player: a case report of angioid streaks.

PMID- 20818201
TI  - Comparison of imaging techniques for diagnosing suspected scaphoid fractures: a
      review.

PMID- 20818202
TI  - Training and detraining in older men.

PMID- 20818203
TI  - Does order of exercising muscle groups affect maximum strength in untrained men?

PMID- 20818204
TI  - Fitness blunts adverse risks of an unhealthy diet.

PMID- 20818205
TI  - Advanced imaging of anterior visual pathway ischemia: state of the art and future
      directions.

PMID- 20818207
TI  - Blurred vision and eye pain in a middle-aged woman.

PMID- 20818206
TI  - The neural mechanism for Latent (fusion maldevelopment) nystagmus.
AB  - Latent nystagmus (LN) is the by-product of fusion maldevelopment in infancy.
      Because fusion maldevelopment--in the form of strabismus and amblyopia--is
      common, LN is a prevalent form of pathologic nystagmus encountered in clinical
      practice. It originates as an afferent visual pathway disorder. To unravel the
      mechanism for LN, we studied patients and nonhuman primates with maldeveloped
      fusion. These experiments have revealed that loss of binocular connections within
      striate cortex (area V1) in the first months of life is the necessary and
      sufficient cause of LN. The severity of LN increases systematically with longer
      durations of binocular decorrelation and greater losses of V1 connections.
      Decorrelation durations that exceed the equivalent of 2-3 months in human
      development result in an LN prevalence of 100%. No manipulation of brain stem
      motor pathways is required. The binocular maldevelopment originating in area V1
      is passed on to downstream extrastriate regions of cerebral cortex that drive
      conjugate gaze, notably MSTd. Conjugate gaze is stable when MSTd neurons of the
      right and left cerebral hemispheres have balanced binocular activity. Fusion
      maldevelopment in infancy causes unbalanced monocular activity. If input from one
      eye dominates and the other is suppressed, MSTd in one hemisphere becomes more
      active. Acting through downstream projections to the ipsilateral nucleus of the
      optic tract, the eyes are driven conjugately to that side. The unbalanced MSTd
      drive is evident as the nasalward gaze-holding bias of LN when viewing with
      either eye.

PMID- 20818208
TI  - The troubles I've seen.
AB  - This Hoyt lecture is composed of 2 topics. First, a series of patients with
      idiopathic intracranial hypertension (IIH) is presented, emphasizing the
      importance of magnetic resonance venography (MRV). Study of the cerebral venous
      sinuses in IIH may demonstrate focal stenosis or venous gaps and represent a
      manifestation of elevated intracranial pressure. Conversely, the clinical picture
      of IIH may occur following cerebral venous sinus thrombosis, and MRV may be
      essential in establishing this diagnosis. In the future, evaluation of flow in
      the cerebral venous sinuses may play an important role in determining the
      potential for visual failure. Second, I will review patients with visual
      cognitive changes, which often go unrecognized. These patients suffer from
      visuoperceptual disturbances, recognizing parts of visual scenes but not the
      entire picture and are unable to comprehend their visual environment. These
      findings are often part of the syndrome of posterior cortical atrophy
      characterized by parieto-occipital atrophy, enlargement of the atrial portion of
      the ventricular system, and diminished metabolic activity in the posterior
      portion of the brain demonstrated with positron emission tomography.

PMID- 20818211
TI  - Richard D. Todd, PhD, MD.

PMID- 20818212
TI  - Good to great-some timely observations.

PMID- 20818213
TI  - Proximal row carpectomy with a dorsal capsule interposition flap.
AB  - Arthritis of the wrist can be a debilitating condition that presents with
      progressive pain and loss of motion. A proximal row carpectomy (PRC) is indicated
      for the management of wrist arthritis and is designed to improve pain while
      maintaining motion. It involves excision of the scaphoid, lunate, and triquetrum
      with the formation of a new articulation between the base of the capitate and the
      lunate fossa of the distal radius. The PRC is a technically straightforward
      procedure that can produce reliable results. It is contraindicated in cases with
      midcarpal arthritis and degeneration of the base of the capitate. In addition,
      there is a question of durability of the new articulation between the capitate
      and the lunate fossa of the distal radius. The use of interposition tissue can
      potentially decrease joint contact pressures and improve long-term durability. A
      PRC technique with the use of an interposition flap based on the dorsal capsule
      of the distal radius is presented.

PMID- 20818214
TI  - Split thickness skin graft removal from free flaps: indications and technique.
AB  - A variety of methods are commonly used in plastic surgery for skin defect
      reconstruction. Split skin graft (SSG) is the most commonly used method in the
      soft tissue defects reconstructive ladder to achieve coverage. One of the most
      distressing postoperative problem associated with SSG is donor site pain because
      of the healing process and the stimulation of nociceptive fibers, which is
      proportional to the size of the harvested area. In the "bowtie scar" method, we
      describe a technique harvesting the SSG in addition to a gracilis-free flap. The
      bowtie scar method is an efficient and economical use of donor tissue from the
      gracilis-free flap. It allows for rapid healing, minimal scarring, and improved
      cosmesis.

PMID- 20818215
TI  - Radial column and volar plating (RCVP) for distal radius fractures with a radial
      styloid component or severe comminution.
AB  - Individual fracture patterns demand specific and adequate fixation. Locked volar
      plating has become popular in the operative fixation of distal radius fractures.
      However, in cases in which there is a radial styloid fragment or in cases of
      severe comminution, the amount of fixation from volar plating alone can be
      inadequate and may lead to loss of reduction. The use of locked radial column
      plates or Kirschner (K) wires provides additional radial column fixation and
      allows the surgeon to tailor the amount of fixation to the individual fracture
      pattern. Outlined here is the technique of combining volar plating with locked
      radial column plating or K-wire fixation, as well as a step-by-step outline to
      help achieve fracture reduction.

PMID- 20818216
TI  - Imaging and anatomic study of the pisiform bone/ulnar nerve relationship
      evaluation of the preferred surgical approach for the excision of the pisiform
      bone.
AB  - This study examines the role of the pisiform bone/ulnar nerve relationship in
      determining the preferred surgical approach for the excision of the pisiform
      bone. An anatomic dissection of Guyon's canal on 10 fresh frozen cadaver wrists
      evenly divided between males and females was combined with magnetic resonance
      imaging (MRI) scans of 10 volunteer wrists. The 3 reported data points include
      the axial images determined on the MRI, the anatomic dissection related to the
      proximity of the ulnar nerve relative to the pisiform in defined positions of the
      wrist and the soft tissue envelope that surrounds the pisiform, and the proximity
      of the ulnar nerve as recorded, measured, and analyzed. An analysis of variance
      of the recorded data points was performed and the statistical results were
      presented (P value of P 05). Dissection and the MRI scans determined that the
      soft tissue envelope between the pisiform and ulnar nerve at Guyon's canal with
      neutral dorsiflexion was 2.5 mm. Palmar flexion was 3.0 mm and neutral flexion
      was 4.5 mm. The thinnest area was adjacent to the ulnar nerve proper on the volar
      radial aspect of the pisiform, on the basis of clock-faced analysis, between the
      3 : 00 and 6 : 00 positions (the pisiform as a circle). The proximity of the
      pisiform in relation to the ulna and the limit of the soft tissue envelope would
      suggest that the preferred surgical approach, or that least likely to cause
      injury to the ulnar nerve, is one that is volar and includes excising the
      pisiform after exposing Guyon's canal.

PMID- 20818217
TI  - Open reduction internal fixation of the unstable mallet fracture.
AB  - Unstable mallet fractures of the digit pose a challenge when treated surgically.
      We present the results of a technique, not earlier described, for the fixation of
      these uncommon injuries. The technique involves anatomical reduction and stable
      fixation of the distal articular fragment combined with stabilization of the
      distal interphalangeal joint with buried Kirschner wires allowing early
      mobilization of the digit. Twenty patients with an average follow-up of 12.7
      months (10 mo to 21 mo) are presented. Results were good/excellent (Crawford's
      criteria) in 16 patients, fair in 3, and poor in 1 with those operated upon
      within 2 weeks postinjury achieving the best results. There were no incidences of
      fixation failure, loss of reduction, or posttraumatic osteoarthritis. One patient
      had a minor infection, but there were no cases of nail deformity or wound
      breakdown. There was high patient satisfaction and all patients returned to work
      after treatment. We conclude that this is a reliable technique with minimal
      complications and is comparable with other published operative and nonoperative
      treatment modalities.

PMID- 20818218
TI  - A new volar vascularization technique using the superficial palmar branch of the
      radial artery for the collapsed scaphoid nonunion.
AB  - Achieving union to prevent scaphoid nonunion advanced collapse wrist in the
      scaphoid nonunion is a challenging clinical problem. Much of the difficulty
      relates to the tenuous blood supply to the scaphoid. One unsolved reconstructive
      problem is the collapsed scaphoid that requires an intercalated wedge graft with
      proximal pole avascular necrosis. We offer a simple technique that only requires
      preservation of the superficial palmar branch of the radial artery that is
      typically ligated during the volar approach to the scaphoid. This technique can
      also be used during any open volar approach to the scaphoid to increase
      vascularity and healing.

PMID- 20818219
TI  - The "Jacobsen flap" technique: a safe, simple surgical procedure to treat
      Dupuytren disease of the little finger in advanced stage.
AB  - The surgery for advanced stages of Dupuytren disease of the little finger is
      controversial. In the literature, several techniques have been described with
      variable reported results and postoperative complications. Percutaneous needle
      fasciotomy, McCash technique, and dermofasciectomy are often performed for
      surgical treatment but they present significant complications and limits. This
      study reviews our experience of using the Jacobsen flap technique, a modification
      of the McCash procedure. We found that the Jacobsen flap technique for the
      significant correction of the contracture, the low rate of complications, and the
      relatively simple surgical approach is an excellent alternative to percutaneous
      needle fasciotomy, dermofasciectomy, or amputation.

PMID- 20818220
TI  - Scaphoid hemiresection and arthrodesis of the radiocarpal joint.
AB  - Radiocarpal arthritis is frequently the result of trauma and/or degenerative
      disease. The leading causes are malunited or nonunited fractures of the radius or
      scaphoid, radiocarpal or intercarpal dislocations or dissociations, or a form of
      primary osteoarthritis or inflammatory arthritis. Management focuses on reducing
      pain, increasing function, and preserving some degree of motion when possible.
      Total wrist arthrodesis remains the ultimate salvage procedure. Several surgical
      procedures attempt to preserve some motion including proximal row carpectomy;
      lunotriquetrocapitohamate (4-corner) or luno-capito-hamate (3-corner) fusion with
      scaphoid excision; radiolunate or radioscapholunate; and lunocapitate
      arthrodesis, and total wrist replacement arthroplasty. These have been used with
      various success rates. The choice of the procedure depends on which
      articulation(s) are diseased and which are spared. Motion-sparing procedures
      require healthy articular cartilage at the site of preserved motion. This paper
      described scaphoid hemiresection and arthrodesis of the radiocarpal joint, the
      SHARC procedure.

PMID- 20818221
TI  - Use of endoprosthetic diaphyseal replacement: a novel approach to management of
      extensive metastatic tumor of the midshaft radius.
AB  - We report the first use of an endoprosthetic diaphyseal replacement after the
      excision of a midshaft radial tumor. We present a rare case of a solitary
      midshaft radial metastasis in a 72-year-old gentleman who was treated 8 years
      earlier for primary renal cell carcinoma by radical nephrectomy. Follow-up for
      this patient was 25 months after implant insertion and at the latest review was
      pain-free. Functional scores for the elbow (using the Mayo Elbow Performance
      Score) and the wrist (using the Mayo Wrist Score) were 80 and 60, respectively,
      both out of 100. Use of a midshaft radial endoprosthesis provides a good
      functional outcome and symptom relief after extensive tumor resection, with
      regard to functional outcome and symptom relief.

PMID- 20818222
TI  - Different surgical approaches to treat chronic tophaceous gout in the hand: our
      experience.
AB  - Chronic tophaceous gout is a disabling erosive arthritis characterized by an
      elevated serum urate concentration, recurrent attacks of arthritis, and deposits
      of monosodium urate crystals in synovial fluids. Tophi, ulcerations of the
      overlying skin, and fissures of the interarticular cartilage may occur in
      advanced stages, combined with deformities of the joints and decreased active
      joint flexion and extension. Although the timely use of allopurinol is associated
      with a decrease in the frequency of deposits of the tophaceous substance,
      however, surgical management is necessary to restore and improve the cosmesis and
      joint function, to alleviate symptomatic discomfort, and to reduce the risk of
      infection when the overlying skin becomes ulcerated. The authors present their
      experience in the surgical management of the chronic tophaceous gout in the hand.

PMID- 20818223
TI  - Reconstruction of volar digital defects: clinical experience with the hipothenar
      flap.
AB  - Soft tissue defects of the little finger especially for flexor injuries located
      on area ll, secondary to traumatic loss or contracture of soft tissue, infection
      or tumor, are challenging procedures for any hand surgeon. The reconstructive
      goal is to provide stable coverage to all noble structures exposed.
      Reconstructive options for this particular area include local, regional and free
      flaps, but all of them offer an important donor site morbidity. We present tree
      clinical cases of soft tissue defects of the little finger using the hipothenar
      fasciocutaneous reversed island flap, designed from the skin located over the
      abductor digiti minimi, which is on the basis of ulnar palmar digital artery. The
      donor site was closed primary. Clinical results were satisfactory and donor site
      wound healing was adequate.

PMID- 20818224
TI  - Olecranon bone graft: revisited.
AB  - Autogenous bone grafts are frequently in use in the field of reconstructive upper
      extremity surgery. Cancellous bone grafts are applied to traumatic osseous
      defects, nonunions, defects after the resection of benign bone tumors,
      arthrodesis, and osteotomy procedures. Cancellous bone grafts do not only have
      benefits such as rapid revascularization, but they also have mechanical
      advantages. Despite the proximity to the primary surgical field, cancellous
      olecranon grafts have not gained the popularity they deserve in the field of
      reconstructive hand surgery. In this study, the properties, advantages, and
      technical details of harvesting cancellous olecranon grafts are discussed.

PMID- 20818225
TI  - Suture suspension arthroplasty technique for basal joint arthritis
      reconstruction.

PMID- 20818226
TI  - Research tip neurotropin incorporated nerve sutures.

PMID- 20818227
TI  - Terlipressin-induced skin necrosis and rhabdomyolysis.

PMID- 20818228
TI  - A new era for antiplatelet therapy in patients with acute coronary syndrome.
AB  - Platelet aggregation is one of the most important underlying mechanisms in acute
      coronary syndromes (ACS). Antiplatelet therapy is considered as a cornerstone
      therapy and is widely used in these patients. Clopidogrel is currently a class I
      indication in patients with ACS. However, different degrees of resistance to
      clopidogrel have been the subject of many recent studies that led to higher
      dosing regimens of clopidogrel. Failure of clopidogrel to provide consistent
      platelet aggregation inhibition in all patients made the emergence of new more
      reliable agents crucial. Prasugrel and ticagrelor are the 2 new antiplatelet
      agents that have recently been compared with clopidogrel in patients with ACS.
      This article reviews the current evidence that supports the use of each of those
      agents and provides clinicians with an objective summary supporting their use.

PMID- 20818229
TI  - Addressing cardiovascular risk in patients with type 2 diabetes: focus on primary
      care.
AB  - Type 2 diabetes is a disorder of glucose and lipid metabolism associated with
      increased risk of macrovascular and microvascular complications. The primary
      focus of treating type 2 diabetes is glycemic control; simultaneous management of
      cardiometabolic risk factors, including blood pressure, lipid profile and
      overweight/obesity, has been shown to improve outcomes. All patients with
      diabetes require individualized combination therapy including diet and exercise
      intervention to help prevent microvascular and macrovascular complications.
      Because primary care physicians in the United States provide the majority of care
      for patients with type 2 diabetes, this article discusses the management of
      cardiovascular risk with a specific focus on primary care. In addition,
      mechanisms by which existing and novel antidiabetes therapies may modulate the
      metabolic pathways and a review of the benefits of cardiovascular risk reduction
      using multifactorial, primary care-focused intervention strategies will be
      discussed. Finally, early- and late-stage disease management strategies are
      discussed.

PMID- 20818230
TI  - Cauliflower urinary bladder caused by multiple diverticula.

PMID- 20818231
TI  - Recruitment maneuver in experimental acute lung injury: the role of alveolar
      collapse and edema.
AB  - OBJECTIVE: In acute lung injury, recruitment maneuvers have been used to open
      collapsed lungs and set positive end-expiratory pressure, but their effectiveness
      may depend on the degree of lung injury. This study uses a single experimental
      model with different degrees of lung injury and tests the hypothesis that
      recruitment maneuvers may have beneficial or deleterious effects depending on the
      severity of acute lung injury. We speculated that recruitment maneuvers may
      worsen lung mechanical stress in the presence of alveolar edema. DESIGN:
      Prospective, randomized, controlled experimental study. SETTING: University
      research laboratory. SUBJECTS: Thirty-six Wistar rats randomly divided into three
      groups (n = 12 per group). INTERVENTIONS: In the control group, saline was
      intraperitoneally injected, whereas moderate and severe acute lung injury animals
      received paraquat intraperitoneally (20 mg/kg [moderate acute lung injury] and 25
      mg/kg [severe acute lung injury]). After 24 hrs, animals were further randomized
      into subgroups (n = 6/each) to be recruited (recruitment maneuvers: 40 cm H2O
      continuous positive airway pressure for 40 secs) or not, followed by 1 hr of
      protective mechanical ventilation (tidal volume, 6 mL/kg; positive end-expiratory
      pressure, 5 cm H2O). MEASUREMENTS AND MAIN RESULTS: Only severe acute lung injury
      caused alveolar edema. The amounts of alveolar collapse were similar in the acute
      lung injury groups. Static lung elastance, viscoelastic pressure, hyperinflation,
      lung, liver, and kidney cell apoptosis, and type 3 procollagen and interleukin-6
      mRNA expressions in lung tissue were more elevated in severe acute lung injury
      than in moderate acute lung injury. After recruitment maneuvers, static lung
      elastance, viscoelastic pressure, and alveolar collapse were lower in moderate
      acute lung injury than in severe acute lung injury. Recruitment maneuvers reduced
      interleukin-6 expression with a minor detachment of the alveolar capillary
      membrane in moderate acute lung injury. In severe acute lung injury, recruitment
      maneuvers were associated with hyperinflation, increased apoptosis of lung and
      kidney, expression of type 3 procollagen, and worsened alveolar capillary injury.
      CONCLUSIONS: In the presence of alveolar edema, regional mechanical
      heterogeneities, and hyperinflation, recruitment maneuvers promoted a modest but
      consistent increase in inflammatory and fibrogenic response, which may have
      worsened lung function and potentiated alveolar and renal epithelial injury.

PMID- 20818232
TI  - Age still matters: prognosticating short- and long-term mortality for critically
      ill patients with pneumonia.
AB  - OBJECTIVE: To determine the association between age and mortality in critically
      ill patients with pneumonia. We hypothesized that increasing age would be
      independently associated with both short- and long-term mortality. DESIGN:
      Prospective population-based cohort study examining the association between age
      and 30-day (short-term) and 1-yr (long-term) mortality using Cox proportional
      hazards regression, adjusting for pneumonia severity, mechanical ventilation,
      sex, functional status, nursing home residence, and having a living will.
      SETTING: Five intensive care units in Edmonton, Alberta, Canada. PATIENTS:
      Critically ill adult patients with pneumonia. MEASUREMENTS AND MAIN RESULTS: The
      cohort included 351 intensive care unit patients; mean age 61 yrs, 59% male, 16%
      from nursing homes. Mean Pneumonia Severity Index was 115 (73% Pneumonia Severity
      Index class IV or V), mean Acute Physiology and Chronic Health Evaluation II
      score 17, and 83% received invasive mechanical ventilation. Overall, 151 (43%)
      were < 60 yrs old, 64 (18%) were 60-69 yrs old, 82 (23%) were 70-79 yrs old, and
      54 (15%) were >= 80 yrs old. By 30 days, 58 of 351 (17%) had died; by 1 yr, 112
      of 351 (32%) had died. Mortality increased with age, 28 of 151 (19%) in those <
      60 yrs, 14 of 64 (22%) in those 60-69 yrs, 39 of 82 (48%) in those 70-79 yrs, and
      31 of 54 (57%) in those >= 80 yrs. Independent of pneumonia severity and other
      factors, age (per 10-yr increase) was associated with 30-day mortality (adjusted
      hazard ratio 1.24, 95% confidence interval 1.03-1.49, p = .026) and 1-yr
      mortality (adjusted hazard ratio 1.39, 95% confidence interval 1.21-1.60, p <
      .001). Having a living will was similarly associated with increased mortality
      (adjusted hazard ratio 3.08, 95% confidence interval 1.61-5.90, p < .001 at 30
      days; adjusted hazard ratio 2.00, 95% confidence interval 1.21-3.32, p = .007 at
      1 yr). CONCLUSIONS: Increasing age was independently associated with risk
      adjusted short- and long-term mortality in critically ill patients with
      pneumonia. These findings may help elderly patients, their families, and
      physicians better understand what intensive care unit admission can offer and
      help them to make more informed decisions.

PMID- 20818233
TI  - Cyst wall puncture and aspiration during EUS-guided fine needle aspiration may
      increase the diagnostic yield of mucinous cysts of the pancreas.
AB  - BACKGROUND: Pancreatic cysts are common, however, their diagnosis and
      classification remains a challenge despite advances in cross-sectional imaging
      and endoscopic ultrasound with fine needle aspiration (EUS-FNA). OBJECTIVE: To
      determine the incremental yield of cytologic examination of material obtained
      from targeted fine needle aspiration ("puncture") of the cyst wall after
      aspiration of fluid for CEA. DESIGN: Retrospective consecutive series. PATIENTS
      AND SETTING: Consecutive patients undergoing EUS-FNA of a pancreatic cyst by 2
      expert endoscopists at a single tertiary care center between January 2006 and
      June 2008. INTERVENTION: Standard EUS-FNA of pancreatic cysts was carried out,
      and after cyst fluid aspiration the cyst wall was punctured and aspirated (CWP)
      to obtain epithelium for cytologic analysis. MAIN OUTCOME MEASUREMENTS: The
      diagnostic yields of carcinoembryonic antigen (CEA) obtained from cyst fluid and
      of cytology obtained from CWP. CEA greater than192 ng/mL was considered
      diagnostic of a mucinous cyst. RESULTS: One hundred seven patients underwent EUS
      FNA with CWP. Sixteen (31%) of 52 patients with CEA <192 ng/mL had cytology
      positive for mucinous epithelium, whereas 15 (47%) of 32 cysts with an
      insufficient amount of fluid for CEA analysis had positive cytology from CWP. The
      additional, cumulative diagnostic yield for mucinous cysts was therefore, 37%. Of
      55 cysts diagnosed as mucinous, more (56%) were diagnosed by CWP cytology alone
      than by CEA (P<0.05). LIMITATIONS: Retrospective design and limited surgical
      pathology. CONCLUSIONS: Cyst wall puncture and aspiration during routine EUS-FNA
      may be a safe, easily applied, and inexpensive technique for improving the
      diagnostic yield for mucinous cysts of the pancreas.

PMID- 20818234
TI  - Fructose malabsorption: true condition or a variance from normality.
AB  - Fructose exists in food naturally or as a sweetening additive. It has been
      thought that fructose malabsorption may cause the gastrointestinal symptoms seen
      in patients with irritable bowel syndrome. However, fructose malabsorption is
      still poorly understood, and clinicians are still uncertain of its role. This
      review attempts to clarify the relation between fructose malabsorption and
      symptoms in normal individuals and patients with irritable bowel syndrome. The
      main problem lies in the diagnosis. First, there is no definite cut off value for
      the breath tests. Second, we are unsure of the normal absorptive capacity of
      fructose in normal individuals. Normal individuals will have a degree of fructose
      malabsorption with or without symptoms depending on the dose of fructose used.
      From earlier studies, 25 g of fructose seems to be the cut-off dose to
      investigate fructose malabsorption, with a positive breath test at this dose
      suggesting abnormally low capacity to absorb fructose. This low level may be
      difficult to exclude from the daily diet, resulting in symptoms of fructose
      malabsorption.

PMID- 20818235
TI  - Safety of blind percutaneous liver biopsy in obese children: a retrospective
      analysis.
AB  - GOAL: To determine the safety and adequacy of blind percutaneous liver biopsy
      (PLB) in obese children. BACKGROUND: PLB is an important diagnostic tool that,
      while invasive, enjoys a relatively low major complication rate. An ever
      increasing reason for pediatric liver biopsy is nonalcoholic fatty liver disease
      associated with obesity. There is a lack of data assessing the safety of liver
      biopsy in obese compared to nonobese children. STUDY: A retrospective study of
      all children over 5 years of age having PLB was conducted. Data collected
      included age, gender, weight, height, BMI, reason for biopsy, number of passes,
      biopsy length, number of portal triads per biopsy, and complication rates.
      RESULTS: A total of 107 biopsies were reviewed. All biopsies were successful.
      Overall, major complications occurred in 1.3% and minor complications in 8.4%;
      there were no deaths. Comparison revealed no difference for number of passes
      (1.5+/-0.7 vs. 1.7+/-0.7), biopsy length (2.0+/-1.3 cm vs. 1.5+/-1.1 cm), number
      of portal tracts per biopsy (9.8+/-5.8 vs. 9.9+/-3.4), or complication rates
      (major: 0% vs. 1.3%; minor: 10.0% vs. 7.8%) between obese and nonobese children.
      CONCLUSION: Blind PLB can be safely carried out in obese children with no
      increase in complication rate compared with nonobese children. Similarly, there
      is no difference in number of passes, biopsy size, portal triads per biopsy, or
      biopsy success for obese children.

PMID- 20818236
TI  - Mild alcohol consumption is not associated with increased fibrosis in patients
      with chronic hepatitis C.
AB  - BACKGROUND: Excessive alcohol consumption is associated with an increased risk
      for fibrosis progression and cirrhosis in patients with chronic hepatitis C virus
      (HCV) infection. However, the impact of mild-moderate alcohol use on the severity
      of liver fibrosis is unclear. GOALS: The objective of this retrospective study
      was to assess the impact of mild alcohol consumption on liver fibrosis in
      patients with chronic HCV. STUDY: 857 patients with well-characterized chronic
      HCV were enrolled. All underwent liver biopsy to assess hepatic fibrosis. The
      duration of HCV infection was determined by detailed questionnaires and personal
      interviews. Alcohol use history was estimated by the Skinner Alcohol Examination
      Questionnaire. Mild alcohol use was defined as 1 to 3 alcoholic beverages/day
      (<30 grams/d). Participants were divided into 4 groups based on their average
      lifetime daily alcohol consumption (essentially none, <1, 1 to 3 or >3 drinks/d)
      and into quartiles based on their presumed duration of HCV infection (<23, 23 to
      31, 31 to 38, or >38 y). RESULTS: Mean alcohol consumption was 2.7 drinks/d; mean
      duration of HCV infection was 29 years. Daily alcohol consumption was not
      significantly higher among participants with advanced fibrosis (bridging fibrosis
      or cirrhosis) when compared with those with none or portal fibrosis (3.2 vs. 2.2
      drinks/d, respectively, P=NS). The degree of fibrosis increased significantly
      with the duration of HCV infection (P<0.0001) and was independent of mild
      moderate alcohol consumption. CONCLUSIONS: Mild alcohol use does not seem to
      adversely affect the severity of fibrosis in patients with chronic HCV.

PMID- 20818237
TI  - Management of war-related burn injuries: lessons learned from recent ongoing
      conflicts providing exceptional care in unusual places.
AB  - Thermal injury is a sad but common and obligatory component of armed conflicts.
      Although the frequency of noncombat burns has decreased, overall incidence of
      burns in current military operations has nearly doubled during the past few
      years. Burn injuries in the military environment do not need to be hostile in
      nature. Burns resulting from carelessness outnumber those resulting from hostile
      action. Unfortunately, civilians are becoming the major targets in modern-day
      conflicts; they account for more than 80% of those killed and wounded in present
      day conflicts. The provision of military burn care mirrors the civilian
      standards; however, several aspects of treatment of war-related burn injuries are
      peculiar to the war situation itself and to the specific conditions of each armed
      conflict. Important aspects of management of burned military personnel include
      triage to ensure that available medical care resources are matched to the
      severity of burn injury and the number of burn casualties, initial management and
      resuscitation in the combat zone, and subsequent evacuation to higher echelons of
      medical care, each with increasing medical capabilities. Care of military victims
      is usually well structured and follows strict guidelines for first aid and
      evacuation to field hospitals by military personnel usually having had some form
      of training in first aid and resuscitation and for which necessary equipment and
      material for such interventions are more or less available. Options available for
      civilian injury intervention in wartime, however, are limited. Of all pre
      hospital transport of civilian victims, 70% are done by lay public and 93%
      receive in the field, or during transport, some form of basic first aid
      administered by relatives, friends, or other first responders not trained for
      such interventions. Civilian casualties frequently represents 60% to 80% of all
      injured admitted to the level III facilities of overseas forces stationed
      throughout the host country. Unlike military personnel who are rapidly evacuated
      to higher echelons IV and V for definitive and long-term care, civilians must
      receive definitive burn treatment at these level III military facilities. The
      present review was intended to highlight peculiar aspects of war-related burn
      injuries of both military personnel and civilians and their management based on
      the most recently published material that, for the most part, is related to the
      recent conflicts in Iraq and Afghanistan.

PMID- 20818238
TI  - Body fat composition and weight changes after double-jaw osteotomy.
AB  - Nutritional problems might be observed after surgical procedures. In this study,
      body weight and fat composition changes have been investigated in dentofacial
      deformity patients after the double-jaw osteotomy procedure. Thirty Angle class 3
      patients operated on with double-jaw osteotomies during the period of March 2006
      to July 2008 were included in the study. Interocclusal splints were applied
      continuously in the first 2 weeks after surgery, whereas intermittent splint was
      used for the next 2 weeks. Patients were analyzed before surgery and on the first
      month after surgery with the help of Tanita Composition Analyzer 310 bioimpedance
      method for weight, fat mass, and fat-free mass values. Results were evaluated
      statistically with the paired-sample test using SPSS version 13.0. Although
      significant results were obtained in female patients before surgery (weight [P =
      0.011], body mass index [BMI; P = 0.012], fat mass [P = 0.010], and fat-free mass
      [P = 0.051, not significant]), none of the values were significant for male
      patients (P = 0.747, P = 0.747, P = 0.645, and P = 0.803, respectively). Weight
      gain was observed in 9 patients (30%). In contrast, weight gain was not seen in
      underweight patients. No sex differences in terms of weight gain/loss and fat
      composition have been observed. Interocclusal splint in female patients operated
      on with double-jaw osteotomies might cause nutritional deficiency in the first
      month after surgery. This eventually causes fat and weight loss, which may lead
      to poor wound healing and recovery later.

PMID- 20818239
TI  - Definition of the lateral bulge deformity after primary cleft lip repair using
      real-time high-resolution ultrasound.
AB  - The lateral bulge is a common secondary deformity after primary cleft lip repair;
      however, its underlying anatomy remains undefined. The purpose of this study was
      to use real-time high-resolution ultrasound to better understand the anatomy
      underlying the lateral bulge deformity. Twenty-three patients with a lateral
      bulge were included in addition to 12 patients without clefts to validate
      ultrasound measurements. Muscle and connective tissue dimensions were recorded at
      standardized landmarks using ultrasound, both at rest and with movement. The
      cleft and noncleft sides (right and left in noncleft patients) were compared
      within groups, and ratios between sides were compared across groups using
      parametric and nonparametric tests. Repeat measurements were recorded to
      calculate intrarater reliability. Orbicularis oris thickness was greater on the
      cleft side in the lateral bulge group at rest, both at the philtral column and
      alar crease (P < 0.001), and with facial movement at the corresponding landmarks
      (alar crease: smile P < 0.001 and pucker P = 0.003; philtral column: smile P <
      0.001 and pucker P = 0.001). The ratio for levator width was also greater in the
      lateral bulge group (P < 0.001). No differences were identified between sides at
      the corresponding landmarks in the noncleft group. Ultrasound enabled real-time
      high-resolution evaluation of anatomic differences underlying the lateral bulge
      deformity. It was associated with greater orbicularis oris thickness and levator
      width on the cleft side. Findings from this study may guide future surgical
      correction of the lateral lip bulge.

PMID- 20818240
TI  - Severity of alveolar cleft affects prognosis of infant orthopedics in complete
      unilateral cleft lip and palate: three-dimensional evaluation from cheiloplasty
      to palatoplasty.
AB  - The purpose of this study was to investigate the relationships between severity
      of alveolar cleft and treatment outcome of infant orthopedics in patients
      affected by complete unilateral cleft lip and palate from cheiloplasty to
      palatoplasty with a three-dimensional evaluation method. Treatment outcomes of
      infant orthopedics were evaluated using three-dimensional linear and angular
      measurements of plaster models after cheiloplasty (T1) and before palatoplasty
      (T2). Eleven patients who had a width of alveolar cleft (WC) less than 4.0 mm at
      T1 (mild group) and 13 patients who had a WC 4.0 mm or greater (severe group)
      were compared and analyzed. From T1 to T2, the lengths of the alveolar segments
      were increased, and the WC was decreased without palatal collapse of alveolar
      segments in both groups. However, the WC in the severe group was significantly
      decreased by increased growth of the major segment compared with the mild group.
      The incisive papilla had a more evoked growth to the alveolar cleft side than in
      the severe group. Conclusively, infant orthopedics was quite useful in reducing
      WC in patients affected by unilateral cleft lip and palate after cheiloplasty,
      and the severity of WC significantly affected the prognosis of infant
      orthopedics.

PMID- 20818241
TI  - Mucociliary function during maxillary sinus floor elevation.
AB  - Maxillary sinus floor elevation carries the potential risk of compromising the
      sinus physiology. The aim of this study was to prospectively assess mucociliary
      function during maxillary sinus augmentation in patients without preoperative
      signs of maxillary sinusitis. Ten patients underwent unilateral sinus floor
      elevation under local anesthesia and endoscopic control. Methylene blue was
      dropped on the floor of the maxillary sinus to evaluate mucociliary function
      until the ostium region during sinus augmentation. The drainage of methylene blue
      was noticed in the lateral, medial, posterior, and anterior walls and in the roof
      of the sinus. As for the sinus floor, only the detached part of mucosa in
      correspondence of the eroded bony window presented not drained methylene blue,
      showing an absence of mucociliary function. Mucociliary function is preserved
      even during the surgical procedure except for the detached area of the
      schneiderian membrane.

PMID- 20818242
TI  - Binder phenotype: associated findings and etiologic mechanisms.
AB  - Binder phenotype (BP), or maxillonasal dysostosis, consists of 6 characteristics:
      arhinoid face, abnormal position of nasal bones, intermaxillary
      hypoplasia/malocclusion, reduced/absent anterior nasal spine, atrophy of nasal
      mucosa, and absence of frontal sinus. The purposes of this study were (1) to
      review the characteristic facial findings, other malformations, and diagnoses in
      8 patients with BP; (2) to compare these patients to those in the literature; and
      (3) to discuss developmental mechanisms, including genetic and environmental
      factors, involved in this facial defect. An initial 24 cases of BP were
      identified from the Iowa Registry of Congenital & Inherited Disorders during the
      period of 1998 to 2008. Chromosome analysis performed in all 24 cases revealed
      the following: trisomy 21, trisomy 18, and mosaic trisomy 18. Of the 24 patients,
      8 met the specific diagnostic characteristics of BP. All 8 patients were
      evaluated in the genetics clinic at University of Iowa Children's Hospital,
      having diagnoses of vitamin K epoxide reductase deficiency, Xp22.3 deletion with
      chondrodysplasia punctata, Stickler syndrome, fetal warfarin syndrome, Robinow
      syndrome, and unknown etiology. This study, unlike those in the literature,
      ascertained cases through a population-based active surveillance registry and
      therefore may better represent the incidence of BP (~1 per 18,000). Most cases
      were sporadic with a recognizable pattern of malformation, highlighting that
      chromosomal, genetic, and exogenous factors may cause BP. Of 8 cases remaining
      after exclusion of chromosome syndromes, 3 cases had in common the involvement of
      the vitamin K-dependent metabolic pathway, which likely represents a significant
      pathogenetic mechanism of BP. Clinical characterization of BP, as in these cases,
      may allow further understanding of other causative developmental mechanisms.

PMID- 20818243
TI  - Intrinsic effects of congenital cleft palate on craniofacial morphology and
      growth characteristics in puberty.
AB  - OBJECTIVES: Of the 12 children in prepuberty (then aged 9 years) with unoperated
      submucous cleft palate where we previously found a characteristic morphology of
      the maxilla, we examined changes in the maxillary morphology in their puberty
      (until age 14 years), aiming to determine the intrinsic effects of congenital
      cleft palate on their craniofacial morphology and growth characteristics, which
      also involve the formation of cranioface, by retrospectively comparing their
      findings and those of noncleft children with normal occlusion. PATIENTS AND
      METHODS: Twelve Japanese children (7 girls and 5 boys) with unoperated submucous
      cleft palate at age 14 years were examined cephalometrically. None of them had
      undergone dentofacial orthopedic treatment of the maxilla. Their craniofacial
      morphologic characteristics were compared with those of 60 Japanese noncleft
      children aged 14 years (30 girls and 30 boys) with normal occlusion. RESULTS: The
      results were nearly identical to the previous findings when they were 9 years
      old: the maxillary length was short, the anterior part of the maxilla being
      retruded and the posterior part of the maxilla being in anterior position in the
      cleft children at age 14 years, compared with the noncleft children. In the
      craniofacial growth changes between the ages 9 and 14 years, an increase in the
      posterior upper facial height was markedly small, and the inclination of the
      palatal plane was promoted in the cleft children, compared with the noncleft
      children. CONCLUSIONS: We confirmed that the intrinsic effects of congenital
      cleft were influential on the morphology of cranioface and its growth changes,
      which also involve craniofacial formation.

PMID- 20818244
TI  - Sinus pericranii--"Don't judge a lump by its surface".
AB  - An interesting and unusual vascular malformation, sinus pericranii is presented.
      Originally referred as a cyst, a "community conundrum" was solved and treated
      successfully in the hospital setting. A discussion of sinus pericranii follows,
      and the teaching values of this particular case are highlighted.

PMID- 20818245
TI  - Isolated fibrous dysplasia of the zygomatic bone.
AB  - Fibrous dysplasia is a nonneoplastic, hamartomatous, developmental disease of the
      bone of obscure etiology. The disease is generally presented as a continuously
      growing, painless mass at late childhood. It is mostly seen in the maxilla and
      the mandible in facial skeleton. Involvement of the zygomatic bone is far rarer.
      Fibrous dysplasia of the zygomatic bone may cause orbital dystopia, diplopia,
      proptosis, loss of visual acuity, swelling, mass formation, or facial asymmetry.
      We present 2 cases of fibrous dysplasia with isolated zygomatic bone involvement.

PMID- 20818246
TI  - Surgical mission (not) impossible--now what?
AB  - International surgical missions, particularly those that address patients with
      clefts of the lip and palate, have become increasingly common. Numerous groups
      have been organized to provide these services. A plastic surgeon participating in
      these endeavors should have full knowledge of the details involved not just for
      himself but to maximize safety and optimize outcomes for these patients. An
      understanding of the issues surrounding trip preparation, the in-country
      logistics, proper preoperative patient selection, and intraoperative and
      postoperative issues are all essential to a successful experience. In this
      article, the authors review and discuss lessons learned from a combined total of
      more than 100 international trips. Relevant literature is reviewed, and
      additional pearls from this body of knowledge are presented.

PMID- 20818247
TI  - Lower lip pits in a patient with van der Woude syndrome.
AB  - van der Woude syndrome (VWS) is a congenital malformation characterized by lower
      lip pits with or without cleft lip or cleft palate. It is an autosomal-dominant
      inherited disorder with variable expression in clinical manifestation.
      Microdeletion in chromosome bands 1q32-q41 and recently identified mutation in
      interferon regulatory factor 6 gene (IRF6) have been reported to cause VWS. We
      report a case of VWS with lower lip pits as its main clinical manifestation
      without associated cleft in lip or palate. No mutation or deletion was found in
      the IRF6 gene or promoter site, indicating the heterogeneity of this defect.

PMID- 20818248
TI  - Diagnosis and management of cephaloceles.
AB  - Cephaloceles are rare neural tube defects. In this study, we retrospectively
      reviewed the charts of all patients with cephaloceles who underwent surgical
      treatment in our institute for a 14-year period, between January 1995 and January
      2009. There were 27 children (11 boys and 16 girls; mean age, 7.5 mo; range, 1 d
      to 7 y). Seventeen encephaloceles were occipital; 5, parietal; 2, ethmoidal; 1,
      frontoethmoidal; 1, nasoethmoidal; and 1, sphenoethmoidal. The mean size of sac
      was 3 cm, although 2 cases of giant occipital encephaloceles were observed. In 19
      cases (70%), the sac contained gliotic brain (encephaloceles) that was excised.
      All patients were operated on in 1 surgical procedure. Hydrocephalus was found in
      16 patients and treated with a ventriculoperitoneal shunt insertion.
      Postoperatively, there was no neurologic deficit or death. After a mean follow-up
      period of 7.2 years (range, 6 mo to 11.5 y), all patients were in good condition.
      In conclusion, occipital cephaloceles are more frequently encountered and are
      usually associated with hydrocephalus. Surgery should be performed as early as
      possible and only after careful preoperative planning especially for the anterior
      cephaloceles.

PMID- 20818249
TI  - A simple solution to a complex position in cleft surgery.
AB  - Correct positioning of the surgeon and patient in palate surgery is a problem
      often faced by the craniofacial surgeon. To achieve the best result, it is
      essential that the surgeon has direct visualization and sufficient access to the
      field. We describe a simple solution to this complex problem, which has been used
      by Dr. Ian Jackson for the last 20 years. We believe the Jackson method of
      positioning offers good visualization of both anterior and posterior parts of the
      palate, while minimizing the strain associated with neck extension during
      conventional positioning in cleft surgery.

PMID- 20818250
TI  - Discussion: Hes1 is required for the development of craniofacial structures
      derived from ectomesenchymal neural crest cells.

PMID- 20818251
TI  - Changing skeletal pattern by means of osteogenesis distraction: a new therapeutic
      approach to patients with dysmorphism.
AB  - The correction of class II high-angle open-bite in patients is difficult to
      achieve by traditional and conventional techniques in occlusal stability and
      function. The authors propose a new approach to a patient with dysmorphism (class
      II, short ramus, and open bite) using distraction osteogenesis to change the
      skeletal pattern of patients with high-angle class II to low-angle class III
      before undergoing traditional orthognathic surgery. This new approach is based on
      osteogenesis distraction, emphasizing planning and surgical procedures.

PMID- 20818252
TI  - Spectrum of Antley-Bixler syndrome.
AB  - Antley-Bixler syndrome (ABS) is an exceptionally rare craniosynostosis syndrome
      characterized by radiohumeral synostosis present from the perinatal period. There
      is a wide spectrum of anomalies seen within ABS, and other features include
      midface hypoplasia; choanal stenosis or atresia; multiple joint contractures;
      visceral anomalies, particularly of the genitourinary system; and impaired
      steroidogenesis. The condition of ABS is curious in that mutations of 2 separate
      genes have been identified and that there seem to be subtle phenotypic
      differences between the 2 genotypes. Mutations of the P450 oxidoreductase gene
      have been reported in those patients with genital anomalies and/or impaired
      steroidogenesis, and the S351C mutation of the fibroblast growth factor receptor
      2 gene has been reported predominantly in those patients with normal genitalia
      and steroidogenesis. We report a series of 4 patients with ABS and review their
      main findings and management.

PMID- 20818253
TI  - Genes, environment, and orofacial clefting: N-acetyltransferase and folic acid.
AB  - Nonsyndromic orofacial clefting has been the subject of intense studies, both
      genetic and epidemiological. The findings have frequently been controversial
      because of lack of reproducibility. Mouse models provide the potential both for
      genetic and environmental uniformity. We have chosen to study the role of genetic
      susceptibility to teratogen-induced orofacial clefting, using 2 drugs (dilantin
      and corticosteroid) and 1 nondrug teratogen (6-aminonicotinamide). The strongest
      single genetic influence we have found is N-acetyltransferase 2. Our recent work
      and that of others suggest that the influence of this locus is mediated through
      alterations in folate metabolism. Our results support epidemiological findings in
      humans and possibly implicate altered cytosine methylation, potentially caused by
      environmental factors, at least in the A/J model.

PMID- 20818254
TI  - Quantitative histomorphometric assessment of regenerate cellularity and bone
      quality in mandibular distraction osteogenesis after radiation therapy.
AB  - BACKGROUND: The use of mandibular distraction osteogenesis (MDO) for tissue
      replacement after oncologic resection in head and neck cancer could have immense
      therapeutic ramifications. We have previously demonstrated significantly
      decreased mechanical and microdensitomeric metrics of our MDO regenerate after 36
      Gy radiation. Quantitative histomorphometry, a third metric, would permit
      objective investigation of the effects of radiation on tissue and cellular
      composition. Our hypothesis is that radiation-induced cellular depletion and
      diminution in function impair optimal bone regeneration. METHODS: Five rats
      received radiation to the left mandible; 5 received none. All animals underwent
      surgical placement of external fixators, creation of mandibular osteotomies,
      distraction to a 5.1-mm gap width, and consolidation. Point counting and color
      thresholding were performed. RESULTS: There was a significant increase in empty
      lacunae and a corresponding diminution in osteocytes after radiation. Whereas the
      volume fraction of mineralized, mature bone was not different, that of
      nonmineralized, immature osteoid was significantly increased in the radiated
      group compared with that in the nonradiated group. CONCLUSIONS: Our findings
      confirm our prior 2 metrics. Actually, all 3 diverse metrics--microdensitometry,
      biomechanical analysis, and histomorphometry--corroborate our hypothesis of
      cellular depletion and diminution of function as the potential mechanism of
      radiation-induced attenuation in the distracted regenerate. Furthermore, our
      findings of tissue and cellular changes in the irradiated regenerate elucidate
      the pathophysiology of decreased bone quality when amalgamated with our previous
      results. Therapeutic agents may now be introduced, and their effects on the
      irradiated regenerate critically measured, so that MDO may be used as a viable
      reconstructive option in patients with head and neck cancer.

PMID- 20818255
TI  - Improving quality of life of children with oral clefts: perspectives of parents.
AB  - Quality of life is increasingly recognized as an important health outcome in
      people with surgically treatable conditions. However, few data are available on
      children with oral clefts. Focus groups provide a rich exploratory approach to
      understanding health-related quality of life issues. We report findings from 2
      focus groups of parents of children with oral clefts (cleft lip, cleft palate,
      and cleft lip and palate) in Utah and Idaho. Participants were guided into a
      discussion of issues and drivers of quality of life, from diagnosis through
      treatment to school entry. Parents identified crucial factors including the early
      need for support (including parent support groups), for credible information, and
      for advice for daily life. Surgery was a major factor affecting satisfaction and
      quality of life, and satisfaction depended not only on surgical results but
      importantly on communication, empathy, expectations, postsurgical care, and
      discharge management. Many parents underscored as critically important the
      preparation and the postsurgery experience, rather than the surgery itself.
      Parents also identified crucial milestones, including birth, diagnosis, the first
      surgery, and school entry. Combining these crucial issues with a life-stage
      approach provides a framework for intervention that focuses on drivers of quality
      of life at selected milestones in the life of children with oral clefts.

PMID- 20818257
TI  - Orbital ectopic brain tissue in Aicardi syndrome.
AB  - BACKGROUND: Aicardi syndrome is a cerebroretinal disorder originally described in
      1965. Its salient clinical features are infantile spasms, agenesis of corpus
      callosum, hypsarrhythmia, and a pathognomonic optic disc appearance consisting of
      multiple depigmented chorioretinal lacunae clustered around the disc. METHODS:
      Clinical report with cranial computed tomography and biopsy results. RESULTS: A 3
      year-old female patient presented with Aicardi syndrome and progressive proptosis
      of the left eye since birth. Visual acuity was light perception only in the right
      eye. Ocular motility examination showed large angle of left exotropia. Direct
      funduscopy showed a large optic nerve head and chorioretinal lacunae in the right
      eye; the left eye was not visible. Magnetic resonance imaging detected a large
      retrobulbar cyst and left microphthalmia. The patient underwent neurosurgery.
      Intraoperative microscopic dissection of the dural membrane led to exposure of an
      underlying cyst, which was 80% resected. Biopsies of walls of the orbital cyst
      showed fragments of neuroglial and meningothelial tissues with some calcification
      and mild chronic inflammation. Psammoma bodies were identified. The diagnosis was
      heterotopic brain tissue. CONCLUSIONS: Heterotopia of brain tissue within the
      orbits is a very rare finding. Two previous reports have described an orbital
      cyst in association with Aicardi syndrome, both attributed to encephaloceles. We
      report a very rare case of heterotopia of brain tissue in Aicardi syndrome. The
      patient did not have an encephalocele.

PMID- 20818256
TI  - Hes1 is required for the development of craniofacial structures derived from
      ectomesenchymal neural crest cells.
AB  - The cranial neural crest cells contribute extensively to the formation of
      skeletogenic mesenchyme in the head and neck. Hes1 functions as a repressor of
      basic helix-loop-helix transcription factors and is implicated in controlling the
      maintenance of undifferentiated cells and the timing of cell differentiation. We
      show here that Hes1 homozygous null mutant mice exhibit multiple craniofacial
      malformations including calvaria agenesis, defective anterior cranial base,
      shortened maxilla and mandible, and abnormal palate and tongue. In the null
      mutant cranium, the calvarial bones, meninges including the dura mater and skin
      were not formed, and the brain was therefore exposed without the outer cover. The
      defective anterior cranial base in the mutants was attributable to the lack of
      presphenoid bone and the flexed cranial base angle, which was in contrast with
      the flat cranial base of wild-type mice. Furthermore, in the null mutants,
      palatal shelf growth was impaired because of the early elevation of the palatal
      shelves, resulting in a narrow palate and oral cavity, which were consistently
      associated with a small size of the tongue. These craniofacial anomalies could be
      the result of the defective development of neural crest cells. Taken together, it
      is supposed that Hes1 signaling plays an essential role in regulating the
      development of various craniofacial structures derived from the cranial neural
      crest cells.

PMID- 20818258
TI  - An unusual amniotic rupture sequence with thoracoabdominal restricting band, low
      set posterior hairline, and trapezius contracture.
AB  - Amniotic rupture sequence is associated with defects of variable severity and at
      different sites. Analysis of the literature reveals difficulties in the
      classification, which, in addition to uncertainties surrounding its causes, make
      diagnosis of unusual presentations rather difficult. We present an unusual case
      of a thoracoabdominal restrictive band from the umbilicus to a low-set posterior
      hairline with severe trapezius contracture, sternoclavicular dislocation, and no
      associated craniofacial or limb abnormalities. Amnion rupture sequence with
      adhesion band seems to be the most probable cause of this rare combination of
      anomalies.

PMID- 20818259
TI  - Importance of muscle movement for normal craniofacial development.
AB  - After the craniofacial structures have completed embryologic development,
      movement of facial muscles begins. Paraxial mesoderm of the first (mastication)
      and second pharyngeal (facial expression) arches gives rise to the muscles of the
      craniofacial area. Muscles derived from the third and fourth pharyngeal arches
      are involved in swallowing and vocalization. For the human newborn face to have a
      normal morphologic appearance, contractions of these muscles must occur to
      stimulate forward growth of bone, cartilage growth, and facial muscle bulk.
      Facial muscles begin to contract between 6 and 8 weeks of embryonic development
      and can be observed on prenatal ultrasound by 9 weeks after fertilization. Lack
      of craniofacial muscle contractions may lead to ocular hypertelorism, flat zygoma
      and midface, high bridge of the nose, depressed tip of the nose, small and open
      mouth, trismus, microretrognathia, small tongue, and abnormal palate (high arch,
      bifid uvula, submucous cleft, and cleft palate).

PMID- 20818260
TI  - Intracranial and extracranial malformations in patients with craniofacial
      anomalies.
AB  - BACKGROUND: Craniofacial structures have an intimate relationship with the
      central nervous system in the embryologic development period and the
      developmental abnormalities of the face and skull that are frequently associated
      with malformations of the central nervous system. Additional intracranial and
      extracranial malformations in a patient with craniofacial deformity may
      negatively affect the outcome of the surgery and the quality of life. PATIENTS
      AND METHODS: A retrospective analysis of a total of 123 patients with
      craniofacial anomalies was performed. Physical examination notes, ophthalmologic
      findings, computed tomography, and magnetic resonance imaging reports were
      retrospectively analyzed, and intracranial and extracranial malformations and
      ophthalmologic problems in each group were categorized. RESULTS: Of the patients
      with nonsyndromic craniosynostosis, 29% had intracranial and extracranial
      malformations. Of them, 17% had ophthalmologic problems. Of the patients with
      syndromic craniosynostosis, 34% had intracranial and 31% had extracranial
      malformations. In the patients with craniofacial cleft, 60% had intracranial and
      30% had extracranial malformations. The most common intracranial malformations
      are hydrocephaly, Chiari type 1 malformation, and corpus callosum disorders.
      CONCLUSIONS: A multidisciplinary approach is essential in the evaluation and
      follow-up of individuals with craniofacial abnormalities. Conventional
      radiography and three-dimensional computed tomography of the bony skeleton and
      axial scanning of the soft tissues is our first-step routine. Brain magnetic
      resonance imaging should be performed in patients with multiple-suture
      synostosis, syndromic synostosis, and craniofacial clefts to rule out central
      nervous system and soft tissue malformations. During the postoperative first
      year, conventional x-rays are sufficient to evaluate the craniofacial area.
      Central nervous system disorders may cause major headaches, muscle weakness,
      hearing problems, extreme fatigue, poor motor coordination, and cognitive and
      social disabilities even when their intelligence quotient is normal. Therefore,
      every effort should be performed to search and treat additional malformations.
      Prevention of additional morbidities improves surgical and social outcomes.

PMID- 20818261
TI  - Tongue suture placement after cleft palate repair.
AB  - OBJECTIVE: Postoperative airway obstruction is a complication of cleft palate
      repair. A technique to control the airway is to place a suture through the tongue
      at the conclusion of the palate repair, but it is not uniformly adopted by
      surgeons. Although it has been frequently performed, the use and effectiveness of
      the tongue suture have not been studied. Our purpose was to determine the
      usefulness of tongue suture placement. DESIGN: We surveyed health care providers
      as to their frequency of use and the value of the tongue suture in postoperative
      airway management of the cleft palate patient. The survey was sent via e-mail to
      2080 members of the American Cleft Palate-Craniofacial Association, with a total
      of 396 responders. RESULTS: Surgeons were nearly equally split on placing a
      tongue suture, with 41.1% responders reporting that they use a tongue suture all
      of the time and 41.1% of responders reporting that they never used a tongue
      suture. Some criterion used for placement was the complexity of the case,
      syndromic patients, and overseas cleft missions. CONCLUSIONS: Many cleft palate
      repairs are done annually without using tongue sutures, but it does not seem to
      affect the outcomes among surgeons, thus confounding the question of
      effectiveness. At this time, tongue suture placement after cleft palate repair is
      variable and subjective. Further studies need to be performed to assess outcomes
      after placing a tongue suture.

PMID- 20818262
TI  - Assessment of serum chromogranin-A as prognostic factor in high-risk prostate
      cancer.
AB  - PURPOSE: The presence of neuroendocrine differentiation may play a key role in
      androgen-independent tumor progression. The prognostic significance of plasma
      chromogranin-A (CgA) was assessed in a series of consecutive patients with high
      risk prostate cancer (PCa). PATIENTS AND METHODS: Twenty-three patients
      presenting high-risk PCa and 8 healthy individuals, as control group, had their
      blood samples collected to evaluate CgA, free and total prostate specific
      antigen, and free and total testosterone in a pilot study. The correlations of
      serum CgA levels with PSA, testosterone, Gleason score, number of foci of
      hypercaptation in bone scan, age, and outcomes were evaluated at baseline and
      after 12 months. RESULTS: Patients with PCa had significantly higher levels of
      plasma CgA (mean, 8.7; range, 1.9-73) than healthy patients (mean, 3.45; range,
      0.6-5.6), P = 0.02. Analyzing only the patients group through correlation of the
      ranks, it was observed that CgA has low, insignificant correlations with PSA (P =
      0.07) and with metastatic extension (P = 0.09). No association was found between
      the plasma CgA levels and the Gleason score (P = 0.20), age (P = 0.15), or
      disease progression (P = 0.27). CONCLUSION: The serum levels of CgA were
      significantly increased in the group with PCa compared with the healthy group.
      However, there were low correlations between serum CgA and known prognostic
      factors (such as total and free PSA, age, Gleason score, and bone metastases) or
      clinical deterioration. Although future studies are needed with larger samples
      and longer follow-up, the presented data envisage a limited role to serum CgA as
      high-risk PCa prognostic factor.

PMID- 20818263
TI  - Esophageal polyp in a boy with eosinophilic esophagitis.

PMID- 20818264
TI  - Inflammatory mediators of esophagitis alter p27 Kip1 expression in esophageal
      epithelial cells.
AB  - BACKGROUND: Barrett esophagus (BE) is a premalignant condition that develops due
      to prolonged gastroesophageal reflux disease (GERD). In some but not all cases,
      BE progresses to Barrett-associated adenocarcinoma. p27 is a tumor-suppressor
      protein that regulates the cell's division cycle and appears to be frequently
      inactivated in Barrett-associated adenocarcinoma due to increased degradation or
      cytoplasmic mislocalization. Reduced or mislocalized p27 would remove it from its
      nuclear targets and result in increased proliferation. Although bile acid and
      hydrochloric acid (HCl) are linked to the pathogenesis of BE, not every patient
      with BE has a history of GERD. Eosinophilic esophagitis mimics GERD, but
      eosinophil granule proteins, known to mediate inflammation, have not been linked
      to BE. It was unknown whether mediators of esophagitis affect p27 expression
      and/or localization in normal esophageal cells. We assessed the effects of bile
      acid, HCl, and eosinophil granule proteins on p27 protein expression,
      localization, and its ability to regulate cell proliferation. MATERIALS AND
      METHODS: Human esophageal epithelial (HET-1A) cells were incubated with
      chenodeoxycholic acid (CDC), HCl, and eosinophil granule proteins (major basic
      protein, MBP; and eosinophil peroxidase, EPO). Cell viability analysis,
      immunoblot, immunofluorescence microscopy, and flow cytometric analysis were
      performed. RESULTS: Exposure of HET-1A cells to CDC, HCl, MBP, and EPO did not
      affect total p27 levels. CDC, HCl, MBP, and EPO caused mislocalization of p27
      from the nucleus to the cytoplasm. Flow cytometry showed that CDC exposure also
      increased HET-1A cell proliferation. CONCLUSIONS: Mislocalization of p27 caused
      by mediators of GERD or eosinophilic esophagitis may serve as an early marker of
      increased cell proliferation, which may contribute to the risk for esophageal
      dysplasia.

PMID- 20818265
TI  - Increased heat shock protein 72 expression in celiac disease.
AB  - BACKGROUND AND OBJECTIVES: Heat shock protein (HSP) 72, a known chaperone, has
      potential epithelial barrier protecting, antiapoptotic, and immune system
      regulatory effects; therefore, our aim was to study its involvement in the
      pathology of celiac disease (CD). PATIENTS AND METHODS: Duodenal biopsy specimens
      were collected from children with untreated and treated CD and from controls.
      mRNA expression, protein level, and localization of HSP72 were determined.
      RESULTS: Elevated HSP72 mRNA expression and higher protein levels were found in
      the duodenal mucosa of children with untreated CD as well as in children with
      treated CD compared with those in controls. In the duodenal mucosa of children
      with treated CD, HSP72 mRNA expression was decreased and HSP72 protein levels
      were lower than those in children with untreated CD. We detected intensive HSP72
      staining in the villous enterocytes and immune cells of the lamina propria in the
      duodenal villi of children with untreated CD compared with that in controls.
      CONCLUSIONS: The increased expression and altered localization of HSP72 in CD
      indicate that HSP72 should have a role in protection against gliadin-induced
      cytotoxicity. HSP72 may exert antiapoptotic effect and contribute to preservation
      of intestinal epithelial barrier integrity. Moreover, HSP72 as a ligand of TLR2
      and TLR4 may promote innate immune responses and warn the cells of the potential
      injury.

PMID- 20818266
TI  - Performing Kasai portoenterostomy beyond 60 days of life is not necessarily
      associated with a worse outcome.
AB  - The introduction of Kasai portoenterostomy has dramatically improved the
      management and survival of children with biliary atresia. The success rate of
      this operation worldwide varies with different centers. In this respect, many
      authors have studied the correlation of a successful outcome with various
      factors, such as the experience and workload of the surgical center, the use of
      postoperative steroids, the underlying biliary anatomy, as well as the age of
      patients at the time of the operation. Indeed, the age of 60 days has been used
      by clinicians as a critical time beyond which the rate of success of the Kasai
      operation markedly reduces. Despite this worldwide adoption, clear evidence
      supporting this critical operative time is still lacking. We undertook a review
      of our experience in the management of children with biliary atresia and focused
      specifically on the issue of the timing of operation. We showed that performing
      the Kasai operation beyond the age of 60 days was not associated with a worse
      outcome and that a high percentage of patients could still achieve good bile flow
      with normal bilirubin postoperatively. Thus, we believe that until the age of 100
      days, the age of the patients does not play a significant role in determining the
      success of the Kasai operation.

PMID- 20818267
TI  - Single-balloon enteroscopy in children: initial experience at a pediatric center.
AB  - Single-balloon enteroscopy (SBE) allows deep endoscopic access to the jejunum and
      ileum in adults; however, there are no published series describing the safety of,
      and indications for, SBE in a pediatric population.Seven pediatric patients (5-17
      years) underwent SBE in a 9-month period. Five of 7 procedures achieved the goal.
      There were no serious complications, and SBE positively affected patient
      management in 5 of 7 cases.We conclude that SBE is feasible in a pediatric
      population and can positively affect patient care.

PMID- 20818268
TI  - Regulatory T cells and T helper subsets in breast-fed infants with hematochezia
      caused by allergic colitis.
AB  - The objective of our study was to investigate the prevalence of CD4 T lymphocyte
      subsets and their commitment to TH1 or TH2 direction in 10 infants with allergic
      colitis (AC) and 10 healthy controls. Infants with AC presented with a higher
      ratio of naive to memory cells, lower prevalence of activated CD4CD25 cells and
      FoxP3 regulatory cells, and a shift to TH2 direction in balance compared with
      controls. These alterations are normalized upon cessation of AC symptoms on
      elemental L-amino acid formula. These findings suggest the importance of antigen
      exposure in AC in infancy.

PMID- 20818269
TI  - A reduced phytate diet does not reduce endogenous fecal zinc in children on a
      habitual high-phytate diet.
AB  - Ten Malawian children, ages 3 to 5 years, at risk for zinc deficiency and
      receiving a habitual maize-based high-phytate diet, received maize after phytate
      reduction for 40 days and had their endogenous fecal zinc (EFZ) measured using
      stable isotope techniques before and after phytate reduction. The phytate:Zn of
      the diet before reduction was 23.0 and afterward was 7.6. EFZ was similar before
      and after dietary phytate reduction, 1.15 +/- 0.33 and 1.17 +/- 0.16 mg/day,
      respectively. EFZ was not affected by dietary phytate in this population.

PMID- 20818270
TI  - Faecal calprotectin in term and preterm neonates.
AB  - OBJECTIVES: The aim of this review was to examine the characteristics of the
      faecal calprotectin assay in neonates and the evidence for its use as a
      noninvasive marker of intestinal illnesses during the neonatal period. METHODS:
      Bibliographic searches were performed in the MEDLINE electronic database up to
      February 2010 looking for the following words (all fields): "infants" or
      "neonates" and "calprotectin." Twenty studies, in which 1180 neonates were
      enrolled, were selected. RESULTS: During the neonatal period, calprotectin levels
      are characterized by significantly higher values in both healthy full-term and
      preterm infants during their first year of life compared with reference values
      established for children and adults. No difference was observed according to
      gestational age or birth weight, whereas a higher faecal calprotectin level was
      detected during intestinal distress in neonates with either inflammatory or
      patent digestive alterations. Despite high interindividual variations, cutoff
      levels are proposed to identify infants with a high risk of intestinal illnesses.
      CONCLUSIONS: Compared with adults and children, healthy full-term and preterm
      neonates have high calprotectin levels. The measurement of calprotectin levels in
      faeces can be a promising noninvasive clinical screening test for intestinal
      distress in neonates.

PMID- 20818271
TI  - A child with myelodysplastic syndrome with hypocellular fibrosis.
AB  - A 9-year-old girl with intractable anemia, rare mucocutaneous bleeding, and
      pallor was presented. Hemoglobin was 49 g/L; reticulocyte 0.79%, mean corpuscular
      volume 81 fL, platelet 37*109/L; white blood cell count 3.2*109/L with dysmorphic
      cells in peripheric blood. Further evaluation revealed 10% cellularity with grade
      IV reticulin fibrosis, immature, and/or dysplastic hematopoietic cells without
      sideroblasts, or blast increase in biopsy, Monosomy 8 was found in bone marrow
      aspiration material using FISH. Vitamin B12, folic acid, hemoglobin
      electrophoresis, immunoglobulin levels, CD55, CD59, complement 3, 4, abdominal
      ultrasonography, chest x-ray were normal; diepoxybutane, acid ham, sucrose lysis
      tests, viral serologies, antinuclear antibody, anti DNA were negative. On
      diagnosis of "Myelodysplastic Syndrome-refractory cytopenia with hypocellular
      fibrosis," she received a successful allogeneic BM transplantation from her full
      matched sibling.

PMID- 20818272
TI  - A calcified mass in the spinal canal of a patient with beta-thalassemia major.

PMID- 20818273
TI  - A calcified mass in the spinal canal of a patient with beta-thalassemia major.

PMID- 20818274
TI  - Early changes in SOFA score as a prognostic factor in pediatric oncology patients
      requiring mechanical ventilatory support.
AB  - PURPOSE: To evaluate whether changes in outcome prediction scores during the
      first 72 hours after admission to a pediatric intensive care unit (PICU) are more
      predictive of outcome than single assessments at admission in pediatric oncology
      patients requiring mechanical ventilatory support for more than 3 days. PATIENTS
      AND METHODS: The medical records of 54 consecutive pediatric oncology patients
      requiring mechanical ventilation over 72 hours in the PICU of the Asan Medical
      Center, Seoul, Korea, between January 2006 and December 2008, were
      retrospectively reviewed. RESULTS: Although both initial Sequential Organ Failure
      Assessment (SOFA) score and change in SOFA score (Delta-SOFA) correlated well
      with mortality, Delta-SOFA score showed a significantly stronger correlation
      (P<0.001) and a larger area under the receiver operating characteristic curve
      than did initial SOFA score. Patients with positive and negative Delta-SOFA
      scores showed statistically significant differences in mortality (18.5% vs.
      88.2%, P<0.001). In addition, early changes in respiratory parameters, such as
      PaO2/FiO2 (P/F) ratio, oxygenation index (OI), and ventilation index (VI),
      evaluated serially during the first 3 days, also correlated with mortality.
      Patients showing improvement in these respiratory parameters displayed
      significantly lower mortality than did patients with worsening of these
      parameters (P<0.01). CONCLUSIONS: Serial evaluation of SOFA score during the
      first few days after PICU admission was a good predictor of prognosis in
      pediatric oncology patients mechanically ventilated over 3 days. Independent of
      initial SOFA score, Delta-SOFA score during the first 72 hours closely correlated
      with outcome. Early changes in respiratory parameters, such as P/F ratio, OI, and
      VI, may also provide valuable prognostic information in such patients.

PMID- 20818275
TI  - Adenocarcinoma of the rectum in a 13-year-old girl with Turner syndrome.
AB  - We describe a 13-year-old girl with short stature and delayed puberty who
      presented with hematochezia and recurrent abdominal pain for 1 year, and
      progressive weight loss for 6 months. Per rectal examination was suggestive of a
      rectal mass. Histopathologic evaluation of the proctoscopy-guided biopsy specimen
      showed rectal adenocarcinoma. Computerized tomography of the abdomen showed
      hepatic metastases, which was confirmed by fine-needle aspiration cytology of the
      liver. She also had perirectal, aortocaval, para-aotic, mesenteric, and
      gastrohepatic ligament lymph node enlargement. GTG-banded chromosomal analysis
      showed a karyotype of 45, X, confirming Turner syndrome. A brief review of the
      neoplasms described in literature in association with Turner syndrome, and the
      possible pathogenetic mechanisms are discussed.

PMID- 20818276
TI  - Bronchial diverticula detected by multidetector-row computed tomography:
      incidence and clinical features.
AB  - PURPOSE: Our aim was to investigate the incidence and characteristics of
      bronchial diverticula using multidetector-row computed tomography (MDCT) and to
      evaluate their association with smoking status. MATERIALS AND METHODS: Two
      radiologists retrospectively reviewed MDCT scans obtained between December 2007
      and February 2008 with a 4-row or a 64-row MDCT scanner for 1122 consecutive
      patients. Bronchial diverticula were assessed for incidence, locations, and
      sizes. Smoking history, including the Brinkman Index, was recorded from clinical
      records. Statistical analysis used chi or t tests to evaluate associations
      between patients' clinical information (age, sex, or smoking history) and the
      presence of bronchial diverticula. RESULTS: A total of 401 bronchial diverticula
      were found in 242 (21.6%) patients (mean, 1.65; mode, 1 per patient). Most
      diverticula were 1 or 2 mm in size. Bronchial diverticula were most frequently
      detected in the subcarinal region. Of these 242 patients with diverticula, 142
      (58.7%) were male and had a higher prevalence than women (P<0.01). No significant
      difference in age was found between the groups with and without bronchial
      diverticula. Although bronchial diverticula were also observed in lifelong
      nonsmokers, the group with bronchial diverticula had a higher percentage of
      smokers than the group without bronchial diverticula (P=0.01). The Brinkman Index
      for the group with bronchial diverticula was significantly higher than for the
      group without diverticula (P<0.01). CONCLUSIONS: Bronchial diverticula are
      frequently observed on chest MDCT scans and are associated with cigarette
      smoking.

PMID- 20818277
TI  - Extrapleural hematomas: imaging appearance, classification, and clinical
      significance.
AB  - PURPOSE: We sought to identify radiologic and clinical findings associated with
      extrapleural hematomas (EPHs), to formulate an imaging-based classification
      system for EPHs, and to identify any radiologic or clinical factors associated
      with surgical intervention. MATERIALS AND METHODS: Thirteen cases of EPH were
      gathered during the clinical review. An EPH was diagnosed on computed tomography
      (CT) if there was inward displacement of extrapleural fat by an intrathoracic
      peripheral fluid collection. The location and shape of each EPH were documented.
      For each case, the chest radiograph obtained in closest proximity to the CT
      acquisitions was also reviewed. The following additional data were also gathered:
      coexistent thoracic and nonthoracic injuries; mechanism of injury; treatment; and
      outcome. RESULTS: In our series, 92% of the patients (12/13) were male. The
      average age of the affected patients was 61 years. Most cases were related to
      blunt trauma (85%, 11/13). All these patients had additional injuries; rib
      fractures were most consistently present (81%, 9/11). All cases could be further
      categorized based on the appearance of their CT scan as biconvex or nonconvex.
      Biconvex EPHs tended to be larger than other types (average size of 4211 mL) and
      required surgical intervention in 80% of patients (4/5). No specific treatment
      was necessary in patients with nonconvex EPHs. CONCLUSIONS: EPHs occur most
      commonly in high-energy blunt trauma; concomitant injuries are the rule,
      especially rib fractures. Biconvex hematomas tend to be large, likely resulting
      from high-pressure bleeding. Consequently, biconvex EPHs more often require
      surgical intervention. Nonconvex hematomas can usually be managed conservatively.

PMID- 20818278
TI  - Repeatability and reproducibility of quantitative whole-lung perfusion magnetic
      resonance imaging.
AB  - PURPOSE: Magnetic resonance imaging (MRI) allows for quantitative evaluation of
      pulmonary perfusion and has shown high clinical usefulness for the evaluation and
      differentiation of different lung pathologies. The reproducibility of
      quantitative analysis of whole-lung perfusion has not been investigated
      previously. Our aim was to assess the intraobserver and interobserver
      repeatability and reproducibility of perfusion MRI to prove the concept that
      perfusion is suitable for therapy monitoring. MATERIALS AND METHODS: The study
      was approved by the International Review Board. Fourteen healthy volunteers were
      examined using a time-resolved FLASH 3-dimensional perfusion sequence (1.5-T MRI,
      TREAT, GRAPPA 2, coronal orientation, voxel size 3.9*3.9*6.3 mm(3)). Perfusion
      was assessed initially and after 24 hours during an inspiratory and an expiratory
      breath hold. For each examination, 0.05 mmol/kg BW of Gd-DTPA was injected.
      Perfusion parameters such as pulmonary blood flow (PBF), pulmonary blood volume,
      and mean transit time were calculated. The evaluation was performed independently
      by 2 blinded observers. Intraobserver and interobserver differences were
      determined. RESULTS: The intraobserver differences between the initial and follow
      up examinations for pulmonary blood volume, mean transit time, and time to peak
      were not significantly different for observers 1 and 2. PBF showed a significant
      difference for both observers only on inspiration (P<0.006 for observer 1 and
      P<0.009 for observer 2). For interobserver evaluation, all parameters, except
      inspiratory PBF, were significantly different (P<0.0001). CONCLUSIONS:
      Intraobserver quantitative perfusion MRI showed reproducible results. However,
      the evaluation is highly dependent on the observer. Therefore, quantitative
      analysis of the serial examinations should be performed by the same observer.

PMID- 20818279
TI  - Double precardinal anastomoses with interconnecting venous plexus hypothesis in
      the embryogenesis of anomalous brachiocephalic veins: computed tomography and
      magnetic resonance findings.
AB  - PURPOSE: The aim of this study was to assess the hypothesis of double precardinal
      transverse anastomoses with an interconnecting venous plexus in the embryogenesis
      of anomalous brachiocephalic veins (ABCV) based on computed tomography (CT) and
      magnetic resonance (MR) findings. MATERIALS AND METHODS: Between January 2000 and
      September 2009, of 25,940 thoracic CT or MR imaging studies, 27 patients with
      developmental ABCV were encountered in our institution. Among them, 15 pediatric
      patients underwent CT or MR studies due to suspected complex thoracic vascular
      anomalies that were not well defined on echocardiograms. In the other 12 adult
      patients, ABCVs were incidentally found during cancer workup or evaluation of
      mediastinal widening seen on the chest radiographs. The anatomic variations of
      ABCV demonstrated on CT or MR imaging were retrospectively reviewed, and the
      implications of ABCV variations in the embryogenesis of ABCV were assessed.
      RESULTS: Five types of ABCV were revealed: supraaortic retrovascular left ABCV
      (n=1), left subaortic ABCV (n=6), double superior venae cavae with hypoplastic
      bridging ABVC (n=5), double superior venae cavae with absence of the
      brachiocephalic vein (BCV) (n=14), and double left BCV (n=1). The 5 types of ABCV
      could be explained by the persistence and regression of different parts of the
      double precardinal transverse anastomoses and interconnecting venous plexus. CT
      also demonstrated interconnecting veins to the BCV in 1 case and nipple-like
      remnants of interconnecting veins on the BCV in 2 cases, providing direct imaging
      evidence of the presence of the interconnecting veins. CONCLUSION: The hypothesis
      of double precardinal anastomoses with interconnecting veins offers a concise but
      comprehensive explanation of various kinds of ABCV.

PMID- 20818280
TI  - Reproducibility-repeatability of choroidal thickness calculation using optical
      coherence tomography.
AB  - PURPOSE: To evaluate the repeatability and reproducibility of subfoveal choroidal
      thickness (CT) calculations performed manually using optical coherence tomography
      (OCT). METHODS: The CT was imaged in vivo at each of two visits on 11 healthy
      volunteers (mean age, 35.72 +/- 13.19 years) using the spectral domain OCT. CT
      was manually measured after applying ImageJ processing filters on 15 radial
      subfoveal scans. Each radial scan was spaced 12 degrees  from each other and
      contained 2500 A-scans. The coefficient of variability, coefficient of
      repeatability (CoR), coefficient of reproducibility, and intraclass correlation
      coefficient determined the reproducibility and repeatability of the calculation.
      Axial length (AL) and mean spherical equivalent refractive error were measured
      with the IOLMaster and an open view autorefractor to study their potential
      relationship with CT. RESULTS: The within-visit and between-visit coefficient of
      variability, CoR, coefficient of reproducibility, and intraclass correlation
      coefficient were 0.80, 2.97% 2.44%, and 99%, respectively. The subfoveal CT
      correlated significantly with AL (R = -0.60, p = 0.05). CONCLUSIONS: The
      subfoveal CT could be measured manually in vivo using OCT and the readings
      obtained from the healthy subjects evaluated were repeatable and reproducible. It
      is proposed that OCT could be a useful instrument to perform in vivo assessment
      and monitoring of CT changes in retinal disease. The preliminary results suggest
      a negative correlation between subfoveal CT and AL in such a way that it
      decreases with increasing AL but not with refractive error.

PMID- 20818281
TI  - Interactions of lens care with silicone hydrogel lenses and effect on comfort.
AB  - PURPOSE: The purpose of this study was to investigate the effect of lens care
      products on short-term subjective and physiological performance silicone hydrogel
      lenses. METHODS: Ten subjects wore either lotrafilcon B or galyfilcon A silicone
      hydrogel contact lenses soaked in a lens care product containing either
      Polyquad/Aldox or PHMB or control lenses inserted directly from the pack.
      Subjects wore the lenses for 6 h. Ocular comfort (graded on a 1 to 10 scale) and
      ocular physiology were assessed. Unworn but soaked lenses were analyzed for
      metrological changes, release of excipients into phosphate buffered saline, and
      changes to their surface chemical composition. RESULTS: None of the lens
      metrology measures or clinically observed conjunctival or limbal redness changed.
      Corneal staining was significantly (p < 0.008) raised, albeit to low levels,
      after 6 h wear for either lens type when soaked in the PHMB solution compared
      with the control lens (lotrafilcon B 0.4 to 0.9 +/- 0.7 to 0.4 vs. 0.1 to 0.4 +/-
      0.3 to 0.5; galyfilcon A 0.2 to 0.3 +/- 0.2 to 0.4 vs. 0.0 +/- 0.0). For
      lotrafilcon B lenses, there were decreases in comfort (p = 0.002), increases in
      burning/stinging (p = 0.002) after 1 h of wear, and increases in lens awareness
      on lens insertion (p = 0.0001) when soaked in PHMB. However, lotrafilcon B lenses
      soaked in Polyquad/Aldox showed increases in burning/stinging after 1 and 6 h (p
      < 0.008) of lens wear. For galyfilcon A lenses, most significant (p <= 0.002)
      changes to symptomatology occurred after soaking in Polyquad/Aldox solution. More
      PHMB was released from lotrafilcon B lenses, and more MPDS material was released
      from galyfilcon A lenses. The surface of galyfilcon A lenses changed but
      irrespective of lens solution type, whereas the changes to the lens surface was
      dependent on solution type for lotrafilcon B lenses. CONCLUSIONS: Lens care
      products can change corneal staining and comfort responses during wear. These
      changes may be associated with release of material soaked into lenses or changes
      to the lens surface composition.

PMID- 20818282
TI  - Transferences of heterocentric astigmatic catadioptric systems including Purkinje
      systems.
AB  - PURPOSE: To develop the linear optics of general catadioptric systems with
      allowance for both astigmatism and heterocentricity. METHODS: Reflecting elements
      partition a catadioptric system into subsystems of four distinct types:
      (unreversed) dioptric subsystems, anterior catoptric subsystems, reversed
      dioptric subsystems, and posterior catoptric systems. Differential geometry of an
      arbitrary astigmatic and tilted or decentered surface is used to determine the
      anterior and posterior catoptric transferences of a surface. RESULTS: The
      transference of a catadioptric system is obtained by multiplication of the
      transferences of unreversed and reversed dioptric subsystems and anterior and
      posterior catoptric transferences of reflecting elements. Formulae are obtained
      for the transferences of the visual system of an eye and of six nonvisual systems
      including the four Purkinje systems. CONCLUSIONS: The transference can be
      calculated for a catadioptric system, and from it, one can obtain other optical
      properties of the system including the dioptric power and the locations of the
      optical axis and cardinal structures.

PMID- 20818283
TI  - Repeatability of peripheral aberrations in young emmetropes.
AB  - PURPOSE: The purpose of this study is to assess the intrasession repeatability of
      ocular aberration measurements in the peripheral visual field with a commercially
      available Shack-Hartmann aberrometer (complete ophthalmic analysis system-high
      definition-vision research). The higher-order off-axis aberrations data in young
      healthy emmetropic eyes are also reported. METHODS: The aberrations of the right
      eye of 18 emmetropes were measured using an aberrometer with an open field of
      view that allows peripheral measurements. Five repeated measures of ocular
      aberrations were obtained and assessed in steps of 10 degrees  out to +/-40
      degrees  in the horizontal visual field (nasal + and temporal -) and -20 degrees 
      in the inferior visual field. The coefficient of repeatability, coefficient of
      variation, and the intraclass correlation coefficient were calculated as a
      measure of intrasession repeatability. RESULTS: In all eccentric angles, the
      repeatability of the third- and fourth-order aberrations was better than the
      fifth and sixth order aberrations. The coefficient of variation was <30% and the
      intraclass correlation coefficient was >0.90 for the third and fourth order but
      reduced gradually for higher orders. There was no statistical significant
      difference in variance of total higher-order root mean square between on- and off
      axis measurements (p > 0.05). The aberration data in this group of young
      emmetropes showed that the horizontal coma (C(3)(1)) was most positive at 40
      degrees  in the temporal field, decreasing linearly toward negative values with
      increasing off-axis angle into the nasal field, whereas all other higher-order
      aberrations showed little or no change. CONCLUSIONS: The complete ophthalmic
      analysis system-high definition-vision research provides fast, repeatable, and
      valid peripheral aberration measurements and can be used efficiently to measure
      off-axis aberrations in the peripheral visual field.

PMID- 20818284
TI  - Programmatic challenges in obtaining and confirming the pneumococcal vaccination
      status of cochlear implant recipients.
AB  - BACKGROUND: Bacterial meningitis represents a substantial concern for individuals
      with cochlear implants (CIs). METHODS: Chart review and direct patient and family
      correspondence to ascertain vaccination status. INTERVENTION: Information
      dissemination via brochure and electronic media, ongoing reminders of the
      importance of vaccination when confirmation of vaccination was not received.
      RESULTS: Marked improvement in vaccination rates ranging from 49% to 99% across
      different patient populations. Importantly, many patients received their
      vaccinations only after follow-up reminders. CONCLUSION: Ensuring optimal
      vaccination of all CI recipients against high-risk pathogens is a significantly
      challenging task. Maximizing vaccination rates in CI users will require an
      ongoing, active effort of information dissemination, documentation of compliance,
      and well-designed behavioral systems to streamline the pragmatic challenges in
      vaccination delivery.

PMID- 20818285
TI  - Listening preference for the native language compared to an unfamiliar language
      in hearing and hearing-impaired infants after cochlear implantation.
AB  - OBJECTIVE: The goal of this study was to investigate the preference for the
      native language compared with an unfamiliar language in normally hearing (NH) and
      hearing-impaired infants with cochlear implants (CIs). BACKGROUND: Preference for
      the native language is an important step in the process of language acquisition
      because it helps infants to attend to the important signals of their environment.
      This preference has been shown very early in the infants' life. In the case of
      infants with CI, it is of interest to determine whether they show similar
      perceptual biases as NH infants despite their impaired auditory system and
      impoverished input provided by the CI device. METHODS: Nine hearing-impaired
      infants with CI (most with 1-2 mo of CI use) and 19 NH infants were tested on
      their preference for their native language (Hebrew child-directed speech)
      compared with a nonnative language (English child-directed speech). The central
      fixation preference procedure was used in which listening times were measured via
      orientation responses of the infant to visual stimuli. RESULTS: 1) Normal hearing
      and infants with CI had perceptual bias for their native language (Hebrew) when
      compared with a nonnative language (English). 2) Infants with CI have shorter
      attention to speech stimuli compared with NH. CONCLUSION: The findings of the
      present study are the first to show that hearing-impaired infants with CI bring
      the same perceptual biases to the task of language learning as NH infants. These
      have important implications on understanding the process by which infants with CI
      acquire language via the CI device.

PMID- 20818286
TI  - Early deterioration in Bell's palsy: prognosis and effect of prednisolone.
AB  - OBJECTIVE: To assess if early deterioration is a negative prognostic factor in
      Bell's palsy and if prednisolone treatment reduces early progression and enhances
      recovery. STUDY DESIGN: Data extracted from the randomized, double-blind, placebo
      controlled multicenter, Scandinavian Bell's palsy study. SETTING: Sixteen
      tertiary referral centers in Sweden and one in Finland. PATIENTS: A total of 829
      patients aged 18 to 75 years with Bell's palsy. INTERVENTION: The study design
      was factorial; 416 patients were given prednisolone, whereas 413 did not receive
      the drug. Data were analyzed with a modified intention-to-treat principle and the
      last-observation-carried-forward method. MAIN OUTCOME MEASURES: Facial function
      was assessed within 72 hours before treatment start, at Days 11 to 17, and at 12
      months. Sunnybrook was used as the main facial grading system with complete
      recovery defined as Sunnybrook 100. RESULTS: In 236 (28%) of 829 patients, the
      palsy deteriorated from baseline to the first follow-up at Days 11 to 17.
      Complete recovery at 12 months was 45% among subjects with early deterioration
      compared with 73% in patients with no initial deterioration (p < 0.0001). In the
      early deterioration group, complete recovery at 12 months was 62% in patients
      treated with prednisolone and 31% in those not treated (p < 0.0001). CONCLUSION:
      Early deterioration in Bell's palsy is a negative prognostic factor for complete
      recovery at 12 months. Prednisolone given within 72 hours may reduce early
      progression and improve the outcome of palsy.

PMID- 20818287
TI  - Current status of bacterial meningitis after cochlear implantation.
AB  - Meningitis after cochlear implantation continues to be a concern. Recent studies
      and anecdotal reports support the belief that intracochlear trauma, lack of
      appropriate immunizations, and a previously used dual-component electrode
      predispose patients to a higher rate of contracting meningitis. In addition, a
      history of meningitis, cochlear dysplasia, and certain variations of surgical
      technique such as the cochleostomy, very young age, immunocompromise, and the
      presence of neural prostheses such as shunts, are all potentially predisposing
      factors. Because many of these factors are beyond our control, there is likely to
      be an inevitable baseline incidence of meningitis, perhaps related to the
      underlying deafness, but by controlling other factors, we can hope to minimize
      the incidence. Despite the efforts of multiple individuals and organizations,
      there continue to be new cases of meningitis, including a small number of
      fatalities, each year. There is recent evidence that a sizeable percentage of
      children with implants have not been vaccinated as suggested by governmental
      agencies, otolaryngologic societies, implant manufacturers, and many cochlear
      implant centers. Clearly, efforts must be made to ensure age-appropriate
      vaccination for all cochlear implant recipients.

PMID- 20818288
TI  - New development in intraoperative video monitoring of facial nerve: a pilot
      study.
AB  - OBJECTIVE: The present study proposes an evolution of an intraoperative video
      based facial nerve monitoring system for otologic and otoneurosurgical procedures
      in comparison with classical electromyographic (EMG) monitoring method. STUDY
      DESIGN: Single-subject design study. SETTING: Tertiary referral center,
      university clinic. PATIENTS: Fifteen patients undergoing a translabyrinthine
      approach for removal of 2 cm or less acoustic neuroma. INTERVENTION:
      Intraoperative monitoring during acoustic neuroma removal. MAIN OUTCOME MEASURES:
      Measurement of mouth angle displacement and EMG peak amplitude at different
      stimulation intensities were measured and compared to evaluate the validity and
      reliability of the proposed new system. RESULTS: The electrophysiologic method
      has been shown to be slightly more sensitive, although it shows limitations
      especially in terms of electrical artifacts during cauterization, totally masking
      the EMG monitoring. CONCLUSION: The present version of video system can be
      considered as valid and reliable as EMG; its main advantages are the absence of
      electrical artifacts, less invasivity, and much less cost.

PMID- 20818290
TI  - Intracochlear recordings of electrophysiological parameters indicating cochlear
      damage.
AB  - OBJECTIVE: : The pathophysiologic mechanisms resulting in hearing loss during
      electrode implantation are largely unknown. To better understand the functional
      implications of electrode implantation, we recorded the effects of cochlear
      damage on acoustically evoked intracochlear measurements using normal-hearing
      gerbils. METHODS: : A metal electrode was placed on the surface of the round
      window, and recordings of the cochlear microphonic (CM) and compound action
      potential (CAP) were made in response to stimulation with tone-bursts at various
      frequencies in 1-octave intervals and at intensities of 15 to 72 dB sound
      pressure level. The electrode was then advanced incrementally, with CM and CAP
      measurements obtained at each step. These data were compared with data obtained
      at the round window, and the electrode was withdrawn when a significant change
      was observed. After electrophysiological analysis, the cochlea was examined
      histologically. RESULTS: : Results show that on electrode insertion, loss of
      amplitude in the CM and CAP occurs after damage to cochlear structures. Loss of
      activity was typically first apparent in the CAP rather than the CM. CONCLUSION:
      : These results suggest that a reduction of the CAP can be an early marker of
      interaction of the electrode with cochlear structures. Such measurements are
      potentially available with slight modifications to current cochlear implant
      technology.

PMID- 20818291
TI  - Describing the trajectory of language development in the presence of severe-to
      profound hearing loss: a closer look at children with cochlear implants versus
      hearing aids.
AB  - OBJECTIVE: The objective of this investigation was to describe the language
      growth of children with severe or profound hearing loss with cochlear implants
      versus those children with the same degree of hearing loss using hearing aids.
      STUDY DESIGN: A prospective longitudinal observation and analysis. SETTING:
      University of Colorado Department of Speech Language and Hearing Sciences.
      PATIENTS: There were 87 children with severe-to-profound hearing loss from 48 to
      87 months of age. INTERVENTION: All children received early intervention services
      through the Colorado Home Intervention Program. Most children received
      intervention services from a certified auditory-verbal therapist or an auditory
      oral therapist and weekly sign language instruction from an instructor who was
      deaf or hard of hearing and native or fluent in American Sign Language. MAIN
      OUTCOME MEASURES: The Test of Auditory Comprehension of Language, 3rd Edition,
      and the Expressive One Word Picture Vocabulary Test, 3rd Edition, were the
      assessment tools for children 4 to 7 years of age. The expressive language
      subscale of the Minnesota Child Development was used in the infant/toddler period
      (birth to 36 mo). RESULTS: Average language estimates at 84 months of age were
      nearly identical to the normative sample for receptive language and 7 months
      delayed for expressive vocabulary. Children demonstrated a mean rate of growth
      from 4 years through 7 years on these 2 assessments that was equivalent to their
      normal-hearing peers. As a group, children with hearing aids deviated more from
      the age equivalent trajectory on the Test of Auditory Comprehension of Language,
      3rd Edition, and the Expressive One Word Picture Vocabulary Test, 3rd Edition,
      than children with cochlear implants. When a subset of children were divided into
      performance categories, we found that children with cochlear implants were more
      likely to be "gap closers" and less likely to be "gap openers," whereas the
      reverse was true for the children with hearing aids for both measures.
      CONCLUSION: Children who are educated through oral-aural combined with sign
      language instruction can achieve age-appropriate language levels on expressive
      vocabulary and receptive syntax ages 4 through 7 years. However, it is easier to
      maintain a constant rate of development rather than to accelerate from birth
      through 84 months of age, which represented approximately 80% of our sample.
      However, acceleration of language development is possible in some children and
      could result from cochlear implantation.

PMID- 20818292
TI  - Effects of early auditory experience on word learning and speech perception in
      deaf children with cochlear implants: implications for sensitive periods of
      language development.
AB  - HYPOTHESIS: That early word learning and speech perception skills have different
      sensitive periods and that very early implantation may affect later vocabulary
      outcomes more than speech perception outcomes. BACKGROUND: Several studies have
      found that deaf children who receive cochlear implants before 3 years of age tend
      to have better speech perception outcomes than children implanted later. Recent
      studies have not found age-at-implantation effects on speech perception or
      central auditory processing among children implanted younger than 2 years,
      suggesting that there may be a sensitive period for speech perception skills that
      closes by around 3 years of age. There has been very little work investigating
      possible sensitive periods for other language skills, such as the ability to
      learn words. Recent work suggests the possibility that the development of word
      learning skills may have an earlier sensitive period than the development of
      speech perception skills. METHODS: Assess speech perception and vocabulary
      outcomes in children implanted before 13 months of age and in children implanted
      between 16 and 23 months of age. RESULTS: Children implanted during the first
      year of life had better vocabulary outcomes than children implanted during the
      second year of life. However, earlier implanted children did not show better
      speech perception outcomes than later implanted children. CONCLUSION: There may
      be an earlier sensitive period for developing the ability to associate the sound
      patterns of words to their referents than for developing speech perception and
      central auditory processing skills.

PMID- 20818294
TI  - A possible association of the norepinephrine transporter gene in the development
      of heroin dependence in Han Chinese.
AB  - OBJECTIVE: Noradrenergic pathways have been suggested to play a crucial role in
      the motivation-reward system of heroin dependence (HD), but so far, the role of
      the human norepinephrine transporter (NET; SLC6A2) gene in the pathogenesis of HD
      has never been investigated. The purpose of this study was to examine whether the
      NET gene is associated with the development of HD, and whether the NET gene
      influences specific personality traits. METHODS: Twelve single-nucleotide
      polymorphisms of the NET gene were analyzed in a case-control study of 965 Han
      Chinese participants (603 patients and 362 controls). All participants were
      screened using a Chinese version of the modified Schedule of Affective Disorder
      and Schizophrenia-Lifetime and all patients met the criteria for HD. A Chinese
      version of the Tridimensional Personality Questionnaire was used to assess
      personality traits and examine the association between specific personality
      traits and NET polymorphisms. RESULTS: No statistically significant differences
      in allele or genotype frequencies were observed in any of the investigated NET
      variants between HD patients and controls. After logistic regression analyses, no
      statistically significant effect of NET variants in the development of HD was
      found. In haplotype analysis, the frequency of AATA haplotype in rs1532701
      rs40434-rs13333066-rs187714 was significantly different between HD patients and
      controls. These NET polymorphisms did not influence novelty seeking and harm
      avoidance scores. CONCLUSION: This study suggests that the NET gene may be
      associated with the development of HD, but not associated with specific
      personality traits among Han Chinese.

PMID- 20818293
TI  - Residual hearing preservation after pediatric cochlear implantation.
AB  - OBJECTIVE: This study is designed to test the hypothesis that preservation of
      residual hearing in a pediatric population is possible using standard electrode
      arrays with full-length insertions. Surgical technique during implantation also
      is described. STUDY DESIGN: Retrospective review of patient medical records.
      SETTING: Academic tertiary care center. PATIENTS: Thirty-one severely to
      profoundly hearing impaired pediatric patients with some residual hearing
      precochlear implantation. INTERVENTION: Cochlear implantation using a modified
      "soft surgery" protocol. MAIN OUTCOME MEASURES: Preimplant and postimplant pure
      tone thresholds and pure-tone average were calculated from unaided preoperative
      and postoperative audiograms from 250, 500, and 1,000 Hz. Hearing preservation
      rates were determined to be complete (loss of <=10 dB), moderate (loss of 11-20
      dB), marginal (loss of 21-40 dB), or none (loss of >40 dB or no response at the
      limits of the audiometer). Functional residual hearing rates (defined in this
      study as at least 1 threshold better than or equal to 75 dB HL for 250, 500, or
      1,000 Hz were calculated. RESULTS: Complete hearing preservation was achieved in
      14 (45.2%) of 31 patients, whereas 28 (90.3%) of 31 had at least partial hearing
      preservation (loss of <=40 dB). The preoperative to postoperative low-frequency
      pure-tone average had a mean change of 18.5 dB and median change of 20 dB. Of the
      patients who had preoperative functional hearing, 9 (50.0%) of 18 maintained
      functional residual hearing postoperatively for at least 1 pitch. CONCLUSION:
      Preservation of residual hearing is feasible in pediatric cochlear implant
      patients using standard-length electrode arrays with full insertions. These data
      have implications for cochlear implantation in pediatric patients who are at
      higher risk of progressive hearing loss than adults.

PMID- 20818295
TI  - Differential impact of the CYP3A5*1 and CYP3A5*3 alleles on pre-dose
      concentrations of two tacrolimus formulations.
AB  - OBJECTIVES: We investigated the pharmacokinetic and pharmacogenetic implications
      of conversion from a twice-daily (P-Tac) to a once-daily (A-Tac) tacrolimus (Tac)
      formulation. METHODS: We analyzed Tac levels in a cohort of 41 renal transplant
      patients with a stable graft function over a period of 1 year before and after
      conversion. RESULTS: After conversion, the patients had, on average,
      significantly lower Tac trough and dose-normalized trough levels (14%, P=0.0004
      and 23%, P=0.001, respectively) despite similar doses. CYP3A5*3/*3 patients
      (n=27) required significantly lower Tac doses with both the formulations to reach
      Tac target levels (P-Tac 39%, P=0.011; A-Tac 36%, P=0.003) compared with *1/*3
      patients (n=13). Interestingly, after the conversion, mean Tac trough levels and
      dose-normalized trough level remained almost constant in *1/*3 patients, but
      decreased significantly in *3/*3 patients (16%, P=0.001 and 25%, P=0.006).
      CONCLUSION: This study provides further evidence that the CYP3A5*1/*3
      polymorphism significantly impacts Tac pharmacokinetics. Moreover, we show for
      the first time a pharmacogenetic effect on two different Tac formulations, as Tac
      trough levels of *3/*3 patients declined significantly after conversion to
      identical A-Tac doses.

PMID- 20818296
TI  - Algorithm for the management of osteoporosis.
AB  - Osteoporosis is a common skeletal disease that weakens bones and increases the
      risk of fractures. It affects about one half of women over the age of 60, and one
      third of older men. With appropriate care, osteoporosis can be prevented; and
      when present, it can be easily diagnosed and managed. Unfortunately, many
      patients with osteoporosis are not recognized or treated, even after sustaining a
      low-trauma fracture. Even when treatment is initiated, patients may not take
      medication correctly, regularly, or for a sufficient amount of time to receive
      the benefit of fracture risk reduction. Efforts to improve compliance and
      treatment outcomes include longer dosing intervals and parenteral administration.
      Clinical practice guidelines for the prevention and treatment of osteoporosis
      have been developed by the National Osteoporosis Foundation (NOF) but may not be
      fully utilized by clinicians who must deal with numerous healthcare priorities.
      We present an algorithm to help streamline the work of busy clinicians so they
      can efficiently provide state-of-the-art care to patients with osteoporosis.

PMID- 20818297
TI  - Deep enteroscopy.
AB  - Obscure gastrointestinal bleeding has long been a challenging dilemma for
      gastroenterologists and primary care providers alike. Although many abnormalities
      can be localized to the small bowel by traditional endoscopic evaluation, deep
      enteroscopy is often needed to evaluate persistent bleeding of unknown etiology
      and other conditions. New technology and developments in endoscopic evaluation
      now provide the necessary tools to explore the small bowel further. These
      techniques, along with the ability to perform therapeutic interventions, have
      significantly advanced the management of patients with occult gastrointestinal
      bleeding and have led to a decline in intraoperative enteroscopy and exploratory
      laparotomy.

PMID- 20818298
TI  - Rhabdomyolysis induced by rosuvastatin and sildenafil.
AB  - A 66-year-old man with diabetes and hypertension using statin was admitted to the
      hospital with progressive myalgia. He had been on rosuvastatin for five months.
      After beginning the use of phosphodiesterase-5 inhibitors, he presented with
      severe muscle pain and maintained penile erection. Several days after
      interruption of therapy, muscle pain and penile erection disappeared. This case
      demonstrates the interaction of sildenafil with rosuvastatin might result in
      myopathy.

PMID- 20818299
TI  - Adverse drug reactions: Part I.
AB  - Pharmacovigilance is the process of identifying, monitoring, and effectively
      reducing adverse drug reactions. Adverse drug reactions (ADRs) are an important
      consideration when assessing a patient's health. The proliferation of new
      pharmaceuticals means that the incidence of ADRs is increasing. The goal for all
      health care providers must be to minimize the risk of ADRs as much as possible.
      Steps to achieve this include understanding the pharmacology for all drugs
      prescribed and proactively assessing and monitoring those patients at greatest
      risk for developing an ADR. Groups at greatest risk for developing ADRs include
      the elderly, children, and pregnant patients, as well as others.
      Pharmacovigilance must effectively be practiced by all health providers in order
      to avoid ADRs.

PMID- 20818300
TI  - Use of statins in patients with chronic hepatitis C.
AB  - Hepatitis C is a leading cause of liver failure and transplantation in the United
      States and a major public health issue. Studies have shown that patients with
      hepatitis C are at an increased risk of cardiovascular disease, which make
      statins of particular benefit in this patient population. However, the National
      Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) lists
      active or chronic liver disease as an absolute contraindication to statin
      therapy. The available literature regarding the safety of statins in this patient
      population is limited, but has not shown clinically significant differences in
      aminotransferase elevations or evidence of hepatotoxicity in patients with
      hepatitis C who have received statins versus those who have not. Statins should
      continue to be avoided in advanced end-stage liver disease, as there is a lack of
      safety data in these patients and drug metabolism would be severely compromised.
      Treatment with statins can be used in those with chronic, stable hepatitis C with
      elevated cardiac risk or a previous cardiac event.

PMID- 20818301
TI  - Freshwater non-O1 Vibrio cholerae infection.
AB  - It is not appreciated by most physicians that vibrio infections can be acquired
      from freshwater exposure. A case of non-O1 Vibrio cholerae urinary tract
      infection associated with freshwater exposure is reported. The potential for
      vibrios to grow in brachish water and for summer heat to cause evaporation
      leading to relative increased salinity in freshwater bodies and the broad
      geographic range of these occurrences to include North American and both eastern
      and western Europe is noted. A literature review of vibrio infection acquired
      from freshwater exposure and the relationship to these epidemiologic and
      pathophysiologic events is discussed.

PMID- 20818302
TI  - Sacrococcygeal yolk sac tumor presenting as subcutaneous fluid collection
      initially treated as abscess.
AB  - Malignant extragonadal germ cell tumors, though more common in infants and
      children, are rare. They occur in the body's midline and may have internal and
      external manifestations. We report a case of an 11-month-old female with
      sacrococcygeal extragonadal yolk sac tumor manifesting as a draining subcutaneous
      nodule after initial treatment as an abscess. Extragonadal germ cell tumors can
      present with external manifestations confusingly similar to other more benign
      soft tissue conditions.

PMID- 20818303
TI  - Vaginal myomectomy in pregnancy: a report of two cases.
AB  - Prolapsed fibroids presenting in pregnancy are rare. Two cases of bleeding
      prolapsed fibroids, one cervical and the other submucosal, are presented to
      demonstrate the clinical features and outcomes following surgical treatment
      during pregnancy. While vaginal myomectomy of a prolapsed cervical fibroid in
      pregnancy appears safe, prolapse of a submucosal fibroid in pregnancy
      necessitating excision may be associated with rupture of the membranes.

PMID- 20818304
TI  - Gastrointestinal stromal tumors and extra-gastrointestinal tract neoplasms.
AB  - OBJECTIVES: Gastrointestinal stromal tumor (GIST) is a relatively uncommon and
      predominantly sporadic tumor of the gastrointestinal tract (GIT). Infrequently,
      it can be associated with other neoplasms, notably GIT carcinomas and, rarely,
      extra-gastrointestinal tumors. Whether this concomitant occurrence is a causal
      association or a coincidence is not yet resolved, nor is its clinical importance
      determined. We attempted to investigate the frequency and spectrum of
      associations between non-incidental GISTs and extra-GIT tumors. METHODS: A
      retrospective review study was carried out over 18 years of records. All
      confirmed cases of GISTs were retrieved from the pathology files of our
      institution. Each case was investigated for any synchronous or metachronous
      association with GIT or extra-GIT tumors. RESULTS: Five (24%) out of 21 cases of
      GISTs were found to be either synchronously or metachronously associated with
      extra-gastrointestinal neoplasms in 55% of the women with GISTs. Males had no
      such association. CONCLUSION: The cause of the association between non-incidental
      GISTs and extra-GIT tumors is difficult to determine. In the majority of cases,
      this association is most likely a coincidental finding. Synchronous occurrence
      with certain tumors, however, may suggest a nonrandom causal association. We
      report a case series study of the possible association of GISTs with extra-GIT
      tumors in female patients. Like other studies, we suggest that patients-
      especially women--with GISTs should be clinically investigated and followed up
      for the possibility of coexisting GIT and extra-GIT neoplasms.

PMID- 20818305
TI  - Effect of sequential treatment as a first-line therapy for Helicobacter pylori
      eradication in patients with diabetes mellitus.
AB  - OBJECTIVES: The Maastricht III Consensus agreed that effective treatment for
      Helicobacter pylori (HP) should achieve an intention-to-treat (ITT) eradication
      rate above 80%, which is still lacking in patients with type 2 diabetes mellitus
      (DM). This pilot study was designed to confirm the efficacy of a 14-day
      sequential treatment regimen in patients with type 2 DM. METHODS: This is a
      prospective, open-label, single-center pilot study. All patients included in this
      study underwent upper gastrointestinal endoscopy. HP status was evaluated in each
      patient by a rapid urease test and histopathologic examination. For seven days,
      all patients received pantoprazole 40 mg twice daily (b.i.d.) and amoxicillin
      1000 mg b.i.d., followed by pantoprazole 40 mg b.i.d., metronidazole 500 mg
      b.i.d., and tetracycline 500 mg four times per day (q.i.d.) [DOSAGE ERROR
      CORRECTED] for the remaining seven days. The study population consisted of 38
      consecutive patients with type 2 DM (18 female, 20 male; mean age 48.0 +/- 12.2
      years), 30 of whom had non-ulcer dyspepsia, four had gastritis, one had gastric
      ulcer, and three had duodenal ulcer disease. Eradication was defined as the
      absence of HP as assessed with the 14C-urea breath test. RESULTS: Thirty-seven of
      38 patients completed the study. All side effects were observed in eight patients
      (21.1%). None of the patients discontinued treatment because of side effects. The
      eradication rate in the DM group was 22/38 (57.9%) for the ITT analysis and 22/37
      (59.5%) for the per-protocol (PP) analysis. CONCLUSION: The results of 14-day
      sequential therapy for the first-line treatment of HP in patients with type 2 DM
      were disappointing. Further studies with new antibiotic combinations are needed
      to find better methods of eradicating HP in patients with type 2 DM.

PMID- 20818306
TI  - Helicobacter pylori eradication in diabetic patients: still far off the treatment
      targets.

PMID- 20818307
TI  - Placental growth factor: a new kid on the block?

PMID- 20818308
TI  - Skin cancer: knowledge, behaviors, and attitudes of college students.
AB  - OBJECTIVES: Knowledge, attitudes, and behaviors of college students regarding
      melanoma and skin protection were examined. METHODS: We surveyed 492 students at
      a mid-sized southern university. The Melanoma Risk Behavior Survey was
      administered in lecture classes. RESULTS: Mean knowledge score was 10.6 +/- 3.8
      (24 questions). A majority of participants knew that sun exposure increases the
      risk for skin cancer; however, only 29% correctly identified behaviors that
      reduce this risk. Mean attitude score was 5.26 +/- 2.73 (11 questions). Sixty
      nine percent agreed that all people should take precautions against skin cancer;
      however, only 51% believed they themselves should practice sun safe behaviors.
      Mean behavior score was 1.29 +/- 1.22 (9 possible). Only 3.1% reported avoiding
      the sun during peak hours, and only 5.1% regularly use sunscreen when exposed to
      the sun. CONCLUSION: Campus programs for increasing awareness of skin cancer risk
      are warranted. Changing attitudes and behaviors regarding exposure and protective
      measures is increasingly important.

PMID- 20818309
TI  - Placental growth factor as short-term predicting biomarker in acute coronary
      syndrome patients with non-ST elevation myocardial infarction.
AB  - OBJECTIVES: The relevance of placental growth factor was analyzed at the
      admission of patients with acute coronary syndrome (ACS) without ST elevation in
      prognosis of fatal outcome after 30 days. METHODS: We collected blood samples
      from 102 ACS patients admitted to the coronary unit with acute chest pain
      manifesting within the last 12 hours. RESULTS: In all 102 admitted patients,
      higher values of placental growth factor (PLGF; >13.2 ng/L, average value)
      indicated a higher risk of fatal outcome (hazard ratio [HR] 2.28, 95% confidence
      interval [CI] 1.21- 4.76, P = 0.0125). PLGF is an important independent
      prognostic marker (adjusted HR 2.35, 95% CI 1.98-4.61, P = 0.1338), and this was
      shown in a multiparameter model, which involved other statistically important
      markers of relative risk (age >65, gender, and estimated glomerular filtration
      rate [eGFR]). CONCLUSION: PLGF levels measured at 12 hours of symptom onset and
      30 days later may independently predict fatal outcome in patients with ACS
      without ST elevation.

PMID- 20818310
TI  - Influenza vaccination acceptance and refusal rates among health care personnel.
AB  - OBJECTIVES: The primary aim of this study was to determine reasons why health
      care personnel (HCP) in a public health department chose or refused free
      influenza vaccinations offered at the worksite. METHODS: In an internal review
      board-approved study, we offered, through a health nurse at the site, self
      administered surveys designed to evaluate HCPs' reasons for choosing or refusing
      influenza vaccination, HCP knowledge of vaccination recommendations, and other
      items such as demographic information. We tested for differences between the
      vaccinated and non-vaccinated cohorts, and conducted multiple logistic regression
      analysis to identify likely predictors of future vaccine acceptance. RESULTS:
      Predictors of vaccine noncompliance were fear of needles (P <= 0.042), fear of
      getting sick from the vaccine (P <= 0.000), disbelief that the vaccine is
      effective (P <= 0.000), ignoring vaccination as a healthy behavior (P <= 0.000),
      and younger age (P <= 0.026). Nonvaccinated HCP were less likely than vaccinated
      HCP to report. Vaccines are encouraged because of (a) minimizing sick days and
      loss of productivity (P <= 0.000); (b) sick patients are exposed to influenza by
      HCP (P <= 0.000); or (c) note any reason (P <= 0.006). CONCLUSION: The non
      vaccinated group refused the vaccine primarily for reasons related to
      misconceptions regarding the effectiveness and health risks of the vaccine, as
      well as a belief that the vaccine is unnecessary. Conversely, the vaccinated
      cohort chose the vaccine for the primary reasons that the vaccine is effective, a
      vaccine is demonstrative of healthy behavior choices, and influenza is
      transmitted both to and from sick patients.

PMID- 20818311
TI  - Pineal germinoma.
AB  - Germinomas are gonadal neoplasms that rarely occur extragonadally in the midline
      structures of the human body. Newly diagnosed adult cases of pineal gland
      germinomas are very rare since most of the cases are diagnosed in the mid teens.
      The estimated incidence of this tumor in western countries is between 0.4-3.4%.
      Typically, this tumor is diagnosed by its characteristic radiological appearance
      alone, supported by tumor marker(s) or by stereotactic biopsy of the tumor. We
      are reporting a very unique case of pineal germinoma diagnosed in an adult at our
      institute by cerebrospinal fluid cytology with literature review. We analyzed
      case reports, literature reviews, and therapy and diagnostic articles about
      pineal germinoma in the English literature from 1983 to 2009 through the national
      library of medicine, Pubmed, and OVID search engines. We used key words "pineal
      germinoma," "pineal gland tumor," "CNS germinoma," and "extragonodal germinomas"
      to search for our articles.

PMID- 20818312
TI  - Necrotizing fasciitis due to an infected urachal cyst in an adult.
AB  - Urachal cyst complications requiring surgical intervention are rarely seen in
      adults, because the urachus is normally obliterated in infancy. Necrotizing
      fasciitis due to an infected urachal cyst in an adult female has not been
      reported. We describe the case of a fifty-year-old female who required aggressive
      surgical management of abdominal wall necrotizing soft tissue infection from an
      infected urachal cyst.

PMID- 20818313
TI  - Osteoporosis: the ignored issue.

PMID- 20818314
TI  - Managing asthma: an evidence-based approach to optimizing inhaled corticosteroid
      treatment.
AB  - Asthma is a chronic disease characterized by airway inflammation and
      hyperresponsiveness and is associated with significant yet avoidable mortality
      and morbidity resulting in considerable individual and societal burden. Inhaled
      corticosteroids are the most effective class of controller medication available
      today for treating persistent asthma and are the evidence-based guideline
      recommended first-line treatment for controlling asthma. Although inhaled
      corticosteroids have proven to reduce asthma-related exacerbations that lead to
      hospitalizations and death, recent studies have shown that only a small
      percentage of patients receive appropriate treatment and monitoring for their
      asthma. Delivering optimal asthma management requires an understanding and
      application of basic science and evidence-based guidelines in clinical practice.
      Management of a chronic disease in the primary care setting requires overcoming
      several barriers due to competing priorities and time constraints of the
      physician, as well as the reluctance of patients to actively participate in their
      own care. However, evidence has shown that the patient-centered medical home
      model can overcome some of these issues and improve patient outcomes and
      adherence to therapy.

PMID- 20818316
TI  - Alagille syndrome: an unusual presentation of an uncommon disease.
AB  - Alagille syndrome is a rare genetic disorder that results in intrahepatic
      cholestasis. Cardiac involvement mainly involves stenosis of branches of the
      pulmonary arteries. Aortic valve involvement is less common. To our knowledge,
      this is the first case of Alagille syndrome associated with severe aortic
      stenosis due to a bicuspid aortic valve.

PMID- 20818315
TI  - Osteoporosis treatment following hip fracture: how rates vary by service.
AB  - OBJECTIVES: Osteoporosis is a prevalent condition among older people. It is often
      undiagnosed until patients suffer fragility fractures. Previous studies have
      shown low rates of initiating osteoporosis treatment during the acute hip
      fracture hospitalization. It is not clear if this varies by the treating service.
      We compared the rates of instituting osteoporosis treatment during the acute
      hospitalization for fragility hip fractures. METHODS: Rates of initiating
      treatment among previously untreated patients were compared between the
      orthopedic, medicine, and rehabilitation services using retrospective cross
      sectional chart review at an academic medical center. Between January 2005 and
      August 2008, 191 patients admitted with a fragility hip fracture survived to be
      discharged from the hospital. RESULTS: There were 67 (35%) patients who were
      started on some form of osteoporosis treatment during their acute hospital stay.
      Factors statistically associated with starting treatment included having a
      discharge diagnosis of osteoporosis (P < 0.0001) and treating service (P <
      0.0001). Orthopedics was the least likely of the 3 treating services to initiate
      treatment, while medicine was the most likely. CONCLUSIONS: Overall rates of
      osteoporosis treatment initiation were low at 35% of the 191 patients' records
      surveyed. Efforts to increase adherence during the acute hospital stay should be
      explored. A promising intervention includes instituting an osteoporosis
      consultative service to improve the likelihood of starting osteoporosis treatment
      post fragility fracture.

PMID- 20818317
TI  - Thrombocytopenia, NAFLD, and metabolic syndrome: is there a link?

PMID- 20818318
TI  - Breast cancer in a patient with agnogenic myeloid metaplasia.

PMID- 20818319
TI  - Progressive multifocal leukoencephalopathy.

PMID- 20818320
TI  - Anomalous left main coronary artery arising from the right sinus of Valsalva in a
      hypertensive woman with chest pain.

PMID- 20818321
TI  - Interventional studies to confirm association of Helicobacter pylori and insulin
      resistance: a winding road.

PMID- 20818322
TI  - Prostate cancer. Saturation biopsy does not accurately localize tumors.
AB  - Precise localization of prostate cancer is essential for the success of focal
      therapies. Despite suggestions that saturation biopsy might be useful in this
      regard, a new study implies it cannot accurately pinpoint prostate tumors.
      research efforts would perhaps be better focused on identifying which patients
      require treatment for clinically localized prostate cancer in the first place.

PMID- 20818323
TI  - Prostate cancer. Socioeconomic status and disparities in treatment patterns.
AB  - Disparities in prostate cancer treatment patterns have been traced to differences
      in socioeconomic status. These results have implications for quality of care
      imparted by health-care providers. until randomized clinical trials establish
      standards of care, physicians must be wary of unconscious bias and strive to
      support, not dictate, the decision-making process.

PMID- 20818324
TI  - Incontinence. Pediatric sacral neuromodulation for refractory incontinence.

PMID- 20818325
TI  - Stones. A matter of doubt--how best to evaluate stone formers.
AB  - Once again the question of one versus two 24 h urine collections for diagnosis in
      kidney stone prevention has been raised. As in all previous studies, no
      difference is seen in the mean levels of analytes between first and second
      collections. However, variation within patients is so marked that at least two
      collections are needed for confidence.

PMID- 20818326
TI  - Prostate cancer screening: current status and future perspectives.
AB  - With the publication of the long-term results of two randomized screening trials
      and updates to screening guidelines from many organizations, the past 2 years
      have been eventful in the field of prostate cancer screening. Both the Prostate,
      Lung, Colorectal and Ovarian Cancer Screening Trial--which failed to identify a
      benefit of screening in a community setting--and the European Randomized Study of
      Screening for Prostate Cancer--which showed a modest benefit to screening in a
      clinical trial setting--have sought to address the role of screening in reducing
      mortality from prostate cancer. Epidemiologic evidence supports the role of PSA
      screening in the stage and grade migration of prostate cancer, but to date the
      evidence for its role in changing mortality patterns is more equivocal. As a
      result, little support exists at present among urologic and cancer prevention
      organizations for population-based PSA screening. Particularly in the USA, where
      PSA screening has been relatively widespread, reductions in prostate-cancer
      specific mortality are likely to be in part related to improvements in treatment,
      rather than solely to PSA screening. The substantial risk of overdiagnosis and
      overtreatment of latent prostate cancer means that methods to increase the
      specificity of prostate cancer screening, and particularly its ability to
      identify high-risk disease, are essential. Strategies such as the use of 5alpha
      reductase inhibitors in high-risk patients, and the continued development of
      urinary and genetic markers hold promise in this regard.

PMID- 20818328
TI  - Urologic trauma guidelines: a 21st century update.
AB  - Trauma is the leading cause of death between the ages of 1 and 44 years in the
      USA. While stabilization of life-threatening injuries is the primary goal in the
      evaluation of all trauma patients, subsequent diagnosis and treatment of
      secondary injuries are requirements for good trauma care. The genitourinary
      system is involved in 10% of trauma cases, and these injuries can be associated
      with considerable morbidity and mortality. Accordingly, physicians involved in
      the initial evaluation and subsequent management of trauma patients should be
      aware of the diagnosis and treatment of injuries that can occur in the
      genitourinary system. In 2009, the European Association of Urology provided
      specific recommendations for the evaluation, diagnosis and management of
      genitourinary trauma. Here, we review and discuss these recommendations in order
      to provide a concise summary for clinicians involved in the evaluation and
      management of trauma patients and their associated genitourinary injuries.

PMID- 20818327
TI  - Therapeutic targeting of the prostate cancer microenvironment.
AB  - Solid tumors can be thought of as multicellular 'organs' that consist of a
      variety of cells as well as a scaffold of noncellular matrix. Stromal-epithelial
      crosstalk is integral to prostate cancer progression and metastasis, and androgen
      signaling is an important component of this crosstalk at both the primary and
      metastatic sites. Intratumoral production of androgen is an important mechanism
      of castration resistance and has been the focus of novel therapeutic approaches
      with promising results. Various other pathways are important for stromal
      epithelial crosstalk and represent attractive candidate therapeutic targets.
      Hedgehog signaling has been associated with tumor progression, growth and
      survival, while Src family kinases have been implicated in tumor progression and
      in regulation of cancer cell migration. Fibroblast growth factors and
      transforming growth factor beta signaling regulate cell proliferation, apoptosis
      and angiogenesis in the prostate cancer microenvironment. Integrins mediate
      communication between the cell and the extracellular matrix, enhancing growth,
      migration, invasion and metastasis of cancer cells. The contribution of stromal
      epithelial crosstalk to prostate cancer initiation and progression provides the
      impetus for combinatorial microenvironment-targeting strategies.

PMID- 20818330
TI  - Fragile privileges: autoimmunity in brain and eye.
AB  - Brain and eye tissues are subject to a reduced version of immune surveillance,
      which has evolved to protect the particularly sensitive tissues from accidental
      bystander damage created by regular inflammatory responses. Yet, there are
      autoimmune diseases in both organs. This review discusses the nature of immune
      reactivity in the healthy eye and brain tissues, and mechanisms that can overcome
      the protective barriers to create tissue specific disease.

PMID- 20818331
TI  - Insight into the molecular mechanism of the multitasking kinesin-8 motor.
AB  - Members of the kinesin-8 motor class have the remarkable ability to both walk
      towards microtubule plus-ends and depolymerise these ends on arrival, thereby
      regulating microtubule length. To analyse how kinesin-8 multitasks, we studied
      the structure and function of the kinesin-8 motor domain. We determined the first
      crystal structure of a kinesin-8 and used cryo-electron microscopy to calculate
      the structure of the microtubule-bound motor. Microtubule-bound kinesin-8 reveals
      a new conformation compared with the crystal structure, including a bent
      conformation of the alpha4 relay helix and ordering of functionally important
      loops. The kinesin-8 motor domain does not depolymerise stabilised microtubules
      with ATP but does form tubulin rings in the presence of a non-hydrolysable ATP
      analogue. This shows that, by collaborating, kinesin-8 motor domain molecules can
      release tubulin from microtubules, and that they have a similar mechanical effect
      on microtubule ends as kinesin-13, which enables depolymerisation. Our data
      reveal aspects of the molecular mechanism of kinesin-8 motors that contribute to
      their unique dual motile and depolymerising functions, which are adapted to
      control microtubule length.

PMID- 20818332
TI  - Proteomic and functional analysis of the mitotic Drosophila centrosome.
AB  - Regulation of centrosome structure, duplication and segregation is integrated
      into cellular pathways that control cell cycle progression and growth. As part of
      these pathways, numerous proteins with well-established non-centrosomal
      localization and function associate with the centrosome to fulfill regulatory
      functions. In turn, classical centrosomal components take up functional and
      structural roles as part of other cellular organelles and compartments. Thus,
      although a comprehensive inventory of centrosome components is missing, emerging
      evidence indicates that its molecular composition reflects the complexity of its
      functions. We analysed the Drosophila embryonic centrosomal proteome using
      immunoisolation in combination with mass spectrometry. The 251 identified
      components were functionally characterized by RNA interference. Among those, a
      core group of 11 proteins was critical for centrosome structure maintenance.
      Depletion of any of these proteins in Drosophila SL2 cells resulted in centrosome
      disintegration, revealing a molecular dependency of centrosome structure on
      components of the protein translation machinery, actin- and RNA-binding proteins.
      In total, we assigned novel centrosome-related functions to 24 proteins and
      confirmed 13 of these in human cells.

PMID- 20818333
TI  - The hsSsu72 phosphatase is a cohesin-binding protein that regulates the
      resolution of sister chromatid arm cohesion.
AB  - Cohesin is a multiprotein complex that establishes sister chromatid cohesion from
      S phase until mitosis or meiosis. In vertebrates, sister chromatid cohesion is
      dissolved in a stepwise manner: most cohesins are removed from the chromosome
      arms via a process that requires polo-like kinase 1 (Plk1), aurora B and Wapl,
      whereas a minor amount of cohesin, found preferentially at the centromere, is
      cleaved by separase following its activation by the anaphase-promoting
      complex/cyclosome. Here, we report that our budding yeast two-hybrid assay
      identified hsSsu72 phosphatase as a Rad21-binding protein. Additional experiments
      revealed that Ssu72 directly interacts with Rad21 and SA2 in vitro and in vivo,
      and associates with sister chromatids in human cells. Interestingly, depletion or
      mutational inactivation of Ssu72 phosphatase activity caused the premature
      resolution of sister chromatid arm cohesion, whereas the overexpression of Ssu72
      yielded high resistance to this resolution. Interestingly, it appears that Ssu72
      regulates the cohesion of chromosome arms but not centromeres, and acts by
      counteracting the phosphorylation of SA2. Thus, our study provides important new
      evidence, suggesting that Ssu72 is a novel cohesin-binding protein capable of
      regulating cohesion between sister chromatid arms.

PMID- 20818334
TI  - An in vivo RNAi assay identifies major genetic and cellular requirements for
      primary piRNA biogenesis in Drosophila.
AB  - In Drosophila, PIWI proteins and bound PIWI-interacting RNAs (piRNAs) form the
      core of a small RNA-mediated defense system against selfish genetic elements.
      Within germline cells, piRNAs are processed from piRNA clusters and transposons
      to be loaded into Piwi/Aubergine/AGO3 and a subset of piRNAs undergoes target
      dependent amplification. In contrast, gonadal somatic support cells express only
      Piwi, lack signs of piRNA amplification and exhibit primary piRNA biogenesis from
      piRNA clusters. Neither piRNA processing/loading nor Piwi-mediated target
      silencing is understood at the genetic, cellular or molecular level. We developed
      an in vivo RNAi assay for the somatic piRNA pathway and identified the RNA
      helicase Armitage, the Tudor domain containing RNA helicase Yb and the putative
      nuclease Zucchini as essential factors for primary piRNA biogenesis. Lack of any
      of these proteins leads to transposon de-silencing, to a collapse in piRNA levels
      and to a failure in Piwi-nuclear accumulation. We show that Armitage and Yb
      interact physically and co-localize in cytoplasmic Yb bodies, which flank P
      bodies. Loss of Zucchini leads to an accumulation of Piwi and Armitage in Yb
      bodies, indicating that Yb bodies are sites of primary piRNA biogenesis.

PMID- 20818335
TI  - Neurotoxicity of Alzheimer's disease Abeta peptides is induced by small changes
      in the Abeta42 to Abeta40 ratio.
AB  - The amyloid peptides Abeta(40) and Abeta(42) of Alzheimer's disease are thought
      to contribute differentially to the disease process. Although Abeta(42) seems
      more pathogenic than Abeta(40), the reason for this is not well understood. We
      show here that small alterations in the Abeta(42):Abeta(40) ratio dramatically
      affect the biophysical and biological properties of the Abeta mixtures reflected
      in their aggregation kinetics, the morphology of the resulting amyloid fibrils
      and synaptic function tested in vitro and in vivo. A minor increase in the
      Abeta(42):Abeta(40) ratio stabilizes toxic oligomeric species with intermediate
      conformations. The initial toxic impact of these Abeta species is synaptic in
      nature, but this can spread into the cells leading to neuronal cell death. The
      fact that the relative ratio of Abeta peptides is more crucial than the absolute
      amounts of peptides for the induction of neurotoxic conformations has important
      implications for anti-amyloid therapy. Our work also suggests the dynamic nature
      of the equilibrium between toxic and non-toxic intermediates.

PMID- 20818336
TI  - An actin-regulated importin alpha/beta-dependent extended bipartite NLS directs
      nuclear import of MRTF-A.
AB  - Myocardin-related transcription factors (MRTFs) are actin-regulated
      transcriptional coactivators, which bind G-actin through their N-terminal RPEL
      domains. In response to signal-induced actin polymerisation and concomitant G
      actin depletion, MRTFs accumulate in the nucleus and activate target gene
      transcription through their partner protein SRF. Nuclear accumulation of MRTFs in
      response to signal is inhibited by increased G-actin level. Here, we study the
      mechanism by which MRTF-A enters the nucleus. We show that MRTF-A contains an
      unusually long bipartite nuclear localisation signal (NLS), comprising two basic
      elements separated by 30 residues, embedded within the RPEL domain. Using siRNA
      mediated protein depletion in vivo, and nuclear import assays in vitro, we show
      that the MRTF-A extended bipartite NLS uses the importin (Imp)alpha/beta
      dependent import pathway, and that import is inhibited by G-actin. Interaction of
      the NLS with the Impalpha-Impbeta heterodimer requires both NLS basic elements,
      and is dependent on the Impalpha major and minor binding pockets. Binding of the
      Impalpha-Impbeta heterodimer to the intact MRTF-A RPEL domain occurs
      competitively with G-actin. Thus, MRTF-A contains an actin-sensitive nuclear
      import signal.

PMID- 20818337
TI  - Biologic profiling of lymph node negative breast cancers by means of microRNA
      expression.
AB  - Breast cancer is a heterogeneous disease. Different subgroups can be recognized
      on the basis of the steroid receptors, HER-2, cytokeratin expression and
      proliferation patterns. As a result of mRNA-profiling studies, five major groups
      can be recognized, of which the triple-negative and basal-like tumors have the
      worst prognosis. Many of these tumors have a high proliferation that has the
      strongest prognostic value in node negative breast cancer. In the current study
      we analyzed the microRNA pattern in 103 lymph node negative breast cancers and
      compared these profiles with different biological characteristics and
      clinicopathological features. Unsupervised hierarchical cluster analysis divides
      the patients into four main groups, of which the basal-like/triple-negative group
      is the most prominent (11% of all cases), the luminal A cancers containing the
      Her2 negative and estrogen receptor/progesterone receptor-positive tumors is the
      largest group (57%), and the group of luminal B (32%) is more heterogeneous and
      contains the Her2 positive/estrogen receptor-negative patients as well. The
      highest overall classification values by analysis of variance followed by cross
      validation (leave one sample out and reselect genes) were found for cytokeratin 5
      and 6, triple-negative and estrogen receptor, with 97, 90 and 90% accuracy,
      respectively. MiR-106b gene is prominent in all of these signatures and
      correlates strongest with high proliferation. Other interesting observations are
      the presence of several microRNAs (miR532-5p, miR-500, miR362-5p, and miR502-3p)
      located at Xp11.23 in cancers with a triple-negative signature, and the
      upregulation of several miR-17 cluster members in estrogen receptor-negative
      tumors. The current study shows that estrogen receptor negativity and cytokeratin
      5 and 6 expression are important, and specific biological processes in lymph node
      negative breast cancer, as microRNA signatures are strongest in these subgroups.

PMID- 20818338
TI  - miRNA expression profiling of lung adenocarcinomas: correlation with mutational
      status.
AB  - MicroRNA (miRNA) expression is deregulated in lung cancer, and some miRNAs are
      associated with poor prognosis and survival. In this study, we investigated the
      miRNA expression in lung adenocarcinomas with different oncogenic mutations,
      including EGFR-positive, KRAS-positive and EGFR/KRAS-negative tumors. The
      expression of 319 miRNAs was evaluated by Exiqon/Luminex microarray, and
      expression of individual miRNAs was validated by individual RT-PCR assays
      (Applied Biosystems). Overall, miRNA expression was similar among three
      mutationally different groups with most upregulated miRNAs being miR-20a, miR
      328, miR-34c and miR-18b and most downregulated miRNAs being miR-32, miR-137 and
      miR-342. Four miRNAs (miR-155, miR-25, miR-495 and miR-7g) were expressed
      differently among these tumors. miR-155 was upregulated only in EGFR/KRAS
      negative group, miR-25 was upregulated only in EGFR-positive group and miR-495
      was upregulated only in KRAS-positive adenocarcinomas. In opposite, let-7g was
      downregulated in all three groups, with more significant downregulation in
      EGFR/KRAS-negative adenocarcinomas. Principal component analysis (PCA) revealed
      significant correlation between miRNA expression patterns and somatic mutations.
      In this study, we demonstrated that despite the similarity in miRNA expression
      among lung adenocarcinomas with different somatic mutations, some miRNAs showed
      unique expression patterns, which were in strong correlation with the mutation
      type, suggesting different carcinogenic pathway for these tumors. These miRNAs
      can be further explored for their diagnostic and prognostic use.

PMID- 20818339
TI  - MicroRNA expression profiling in benign (sporadic and hereditary) and recurring
      adrenal pheochromocytomas.
AB  - MicroRNAs are involved in the pathogenesis of several tumors, however, there have
      been no data on microRNA expression in pheochromocytomas to date. The objective
      of our study was to perform microRNA expression profiling in sporadic and
      hereditary benign, and recurring adrenomedullary tumors. Furthermore, the
      applicability of formalin-fixed paraffin-embedded tissue samples for the analysis
      of microRNA expression in pheochromocytomas was examined. MicroRNA expression
      data of three matched frozen and formalin-fixed paraffin-embedded samples were
      correlated. A total of 21 formalin-fixed paraffin-embedded samples (sporadic
      benign, multiple endocrine neoplasia 2, von Hippel-Lindau disease, sporadic
      recurring) were subjected to microRNA expression profiling using microarrays.
      MicroRNAs with significant differences in expression were validated and sample
      sizes were extended including tumors from neurofibromatosis type 1 patients by
      real-time quantitative reverse-transcription PCR (n=33). MicroRNA target
      prediction was carried out by TargetScan and MicroCosm Targets. Pathway analysis
      of targets was performed by Ingenuity Pathway Analysis and DIANA mirPath.
      Furthermore, microRNA expression profiles of a malignant pheochromocytoma and a
      pair of primary and recurrent tumors were studied by TaqMan Human MicroRNA Cards.
      MicroRNA expression correlated well between frozen and formalin-fixed paraffin
      embedded samples (70-92%). Microarray analysis revealed 16 significantly
      differentially expressed microRNAs. Five of these were validated by real-time RT
      PCR. miR-139-3p, miR-541 and miR-765 were significantly differentially expressed
      between sporadic benign and von Hippel-Lindau-related pheochromocytomas.
      Significantly higher expression of miR-885-5p and miR-1225-3p was found in
      multiple endocrine neoplasia type 2 and sporadic recurring pheochromocytomas,
      respectively. Pathway analysis revealed the possible involvement of Notch- and G
      protein-coupled receptor signaling in tumor recurrence. MicroRNA expression
      profiles in the primary recurrent and recurring malignant comparisons have been
      similar. In conclusion, we have proved that formalin-fixed paraffin-embedded
      samples can be used for the analysis of microRNA expression in pheochromocytomas.
      MicroRNA expression patterns differ between various sporadic, hereditary and
      recurring tumors and miR-1225-3p may be useful for identifying recurring
      pheochromocytomas.

PMID- 20818341
TI  - E-cadherin expression in plasmacytoid, signet ring cell and micropapillary
      variants of urothelial carcinoma: comparison with usual-type high-grade
      urothelial carcinoma.
AB  - Loss of E-cadherin expression has been linked to the invasive phenotypes of a
      variety of neoplasms, including lobular breast cancer. The expression of E
      cadherin in variants of urothelial carcinoma relative to usual-type urothelial
      carcinoma, maximum depth of invasion and angiolymphatic invasion has not been
      well characterized. A total of eight cases of micropapillary urothelial
      carcinoma, four cases of plasmacytoid urothelial carcinoma, two cases of
      urothelial carcinoma with signet ring cell differentiation and two cases of
      urothelial carcinoma with mixed plasmacytoid and signet ring cell
      differentiation, all obtained from cystectomy/cystoprostatectomy cases, were
      identified. In all nine cases of usual-type invasive and noninvasive high-grade
      urothelial carcinoma were also included in the study. Immunohistochemical
      staining of E-cadherin was performed in all cases. Pathological parameters
      including depth of invasion and presence of angiolymphatic invasion were
      documented. Maximum depth of invasion: In micropapillary urothelial carcinoma,
      extravesical extension was seen in three of eight cases; muscularis propria
      invasion in four of eight cases; and lamina propria invasion in one of eight
      cases. In plasmacytoid urothelial carcinoma, extravesical extension was observed
      in two of four cases, and muscularis propria invasion and lamina propria invasion
      in one of four cases each. In urothelial carcinoma with signet ring cell
      differentiation, extravesical extension and muscularis propria invasion was seen
      in one of two cases each. In urothelial carcinoma with mixed plasmacytoid and
      signet ring cell differentiation, muscularis propria invasion and lamina propria
      invasion was observed in one of two cases each. In usual-type high-grade
      urothelial carcinoma, extravesical extension was seen in six of nine cases and
      noninvasive in three of nine cases. In angiolymphatic invasion, micropapillary
      urothelial carcinoma was observed in eight of eight cases; plasmacytoid
      urothelial carcinoma in two of four cases; urothelial carcinoma with signet ring
      cell differentiation in one of two cases; and urothelial carcinoma with mixed
      plasmacytoid and signet ring cell differentiation in one of two cases. Usual-type
      high-grade urothelial carcinoma was seen in six of nine cases. E-cadherin
      expression: All eight cases of micropapillary urothelial carcinoma were positive
      for E-cadherin in the micropapillary component and adjacent usual-type urothelial
      carcinoma. The four cases of plasmacytoid urothelial carcinoma, two cases of
      urothelial carcinoma with signet ring cell differentiation and two cases of
      urothelial carcinoma with mixed plasmacytoid and signet ring cell differentiation
      were all negative for E-cadherin. All nine additional cases of usual-type high
      grade urothelial carcinoma were diffusely positive for E-cadherin. E-cadherin is
      diffusely positive in usual-type urothelial carcinoma and micropapillary
      urothelial carcinoma, irrespective of pathological stage and angiolymphatic
      invasion. Loss of E-cadherin expression may be a marker of plasmacytoid and
      signet ring cell differentiation in urothelial carcinoma.

PMID- 20818340
TI  - International Society of Urological Pathology (ISUP) Consensus Conference on
      Handling and Staging of Radical Prostatectomy Specimens. Working group 2: T2
      substaging and prostate cancer volume.
AB  - The 2009 International Society of Urological Pathology consensus conference in
      Boston made recommendations regarding the standardization of pathology reporting
      of radical prostatectomy specimens. Issues relating to the substaging of pT2
      prostate cancers according to the TNM 2002/2010 system, reporting of tumor
      size/volume and zonal location of prostate cancers were coordinated by working
      group 2. A survey circulated before the consensus conference demonstrated that
      74% of the 157 participants considered pT2 substaging of prostate cancer to be of
      clinical and/or academic relevance. The survey also revealed a considerable
      variation in the frequency of reporting of pT2b substage prostate cancer, which
      was likely a consequence of the variable methodologies used to distinguish pT2a
      from pT2b tumors. Overview of the literature indicates that current pT2
      substaging criteria lack clinical relevance and the majority (65.5%) of
      conference attendees wished to discontinue pT2 substaging. Therefore, the
      consensus was that reporting of pT2 substages should, at present, be optional.
      Several studies have shown that prostate cancer volume is significantly
      correlated with other clinicopathological features, including Gleason score and
      extraprostatic extension of tumor; however, most studies fail to demonstrate this
      to have prognostic significance on multivariate analysis. Consensus was reached
      with regard to the reporting of some quantitative measure of the volume of tumor
      in a prostatectomy specimen, without prescribing a specific methodology.
      Incorporation of the zonal and/or anterior location of the dominant/index tumor
      in the pathology report was accepted by most participants, but a formal
      definition of the identifying features of the dominant/index tumor remained
      undecided.

PMID- 20818342
TI  - Aberrant expression of cytokeratin 7 in perivenular hepatocytes correlates with a
      cholestatic chemistry profile in patients with heart failure.
AB  - A cholestatic liver chemistry profile (elevations in alkaline phosphatase and
      bilirubin) is commonly encountered in patients with hepatic venous outflow
      obstruction due to right heart failure. Liver biopsies from these patients
      demonstrate varying degrees of sinusoidal dilatation, red blood cell
      extravasation and sinusoidal congestion. Recently, a bile ductular reaction
      mimicking biliary tract disease has been identified in ~ 50% of patients with
      venous outflow obstruction possibly explaining the cholestatic profile
      encountered in these patients. In this study, we evaluated the liver biopsies
      from 22 patients with heart failure. Marked sinusoidal dilatation involving zones
      2 and 3 was observed in 15 patients. Similar to a previous study, 7 of 22
      patients had histologic evidence of a mild ductular reaction. Cytokeratin 7
      immunohistochemistry revealed a mild ductular reaction in an additional two
      cases. Strikingly, CK7 was aberrantly expressed in perivenular hepatocytes in 20
      of 22 cases. Perivenular CK7 immunoreactivity was focal in most cases; however,
      in five cases it was quite extensive and extended into zone 2. There was no
      significant association between marked sinusoidal dilatation and extensive
      perivenular CK7 positivity. Extensive perivenular CK7 positivity was
      significantly associated with both elevated bilirubin, as well as the presence of
      fibrosis. However, a ductular reaction was not associated with a cholestatic
      liver chemistry profile.

PMID- 20818345
TI  - Revisiting the goldilocks phenomenon: folate and colorectal cancer risk.

PMID- 20818346
TI  - A specialized, nurse-run titration clinic: a feasible option for optimizing beta
      blockade in non-clinical trial patients.
AB  - OBJECTIVES: Randomized controlled trials of variceal bleeding prophylaxis
      demonstrate beta-blocker (BB) withdrawal rates of about 15%. We aimed to evaluate
      the dosing and tolerance of BBs achievable in a specialized, nurse-run BB
      titration clinic with non-trial participants. METHODS: We analyzed prospectively
      collected data from 154 patients seen at the clinic between 2004 and 2009. BBs
      were titrated to patient tolerance. The therapeutic target (TT) was defined as a
      heart rate between 50 and 60 beats per minute (bpm) on the last clinic visit
      and/or maximum doses of BBs (propranolol 320 mg, nadolol 160 mg). RESULTS: Eight
      of 154 patients were lost to follow-up, leaving 146. Fifty-five percent were male
      (mean age, 55; mean model for end-stage liver disease (MELD) score, 9), with 74%
      Child-Pugh class A. Median end-of-study doses were 120 mg propranolol and 60 mg
      nadolol. Seventy-nine percent of patients reached the TT before they were
      discharged from the clinic. Side effects were experienced by 72% of patients.
      Thirty-four percent had no need for dose reduction; 17% required transient dose
      reduction, 16% permanent dose reduction, and 5% BB discontinuation. Among
      patients requiring permanent dose reduction or discontinuation, the top reasons
      were fatigue and orthostatic symptoms. Independent predictors of achieving higher
      doses of BB were the absence of side effects, younger age, and diabetes.
      CONCLUSIONS: This study provides evidence that a specialized BB titration clinic
      attains low withdrawal rates and higher doses, similar to those in clinical
      trials. Nurse-led clinics can contribute to successful titration of these
      important medications.

PMID- 20818343
TI  - International Society of Urological Pathology (ISUP) Consensus Conference on
      Handling and Staging of Radical Prostatectomy Specimens. Working group 4: seminal
      vesicles and lymph nodes.
AB  - The 2009 International Society of Urological Pathology Consensus Conference in
      Boston made recommendations regarding the standardization of pathology reporting
      of radical prostatectomy specimens. Issues relating to the infiltration of tumor
      into the seminal vesicles and regional lymph nodes were coordinated by working
      group 4. There was a consensus that complete blocking of the seminal vesicles was
      not necessary, although sampling of the junction of the seminal vesicles and
      prostate was mandatory. There was consensus that sampling of the vas deferens
      margins was not obligatory. There was also consensus that muscular wall invasion
      of the extraprostatic seminal vesicle only should be regarded as seminal vesicle
      invasion. Categorization into types of seminal vesicle spread was agreed by
      consensus to be not necessary. For examination of lymph nodes, there was
      consensus that special techniques such as frozen sectioning were of use only in
      high-risk cases. There was no consensus on the optimal sampling method for pelvic
      lymph node dissection specimens, although there was consensus that all lymph
      nodes should be completely blocked as a minimum. There was also a consensus that
      a count of the number of lymph nodes harvested should be attempted. In view of
      recent evidence, there was consensus that the diameter of the largest lymph node
      metastasis should be measured. These consensus decisions will hopefully clarify
      the difficult areas of pathological assessment in radical prostatectomy
      evaluation and improve the concordance of research series to allow more accurate
      assessment of patient prognosis.

PMID- 20818347
TI  - The clinical evolution of inflammatory bowel disease, 1960-2010: an eyewitness
      account.

PMID- 20818351
TI  - FIT: a valuable but underutilized screening test for colorectal cancer-it's time
      for a change.
AB  - Although fecal immunochemical tests (FITs) have been used for colorectal cancer
      (CRC) screening in several countries for years, this has not been the case in the
      United States. The reasons for this are multifactorial, but if the United States
      hopes to increase screening rates, the evidence is in regarding FIT's benefits
      and potential. A publication in this issue of the American Journal of
      Gastroenterology provides "gold standard" evidence of its superiority over the
      standard guaiac test and opens opportunities for investigators to discover the
      most effective uses of this test for population screening.

PMID- 20818348
TI  - Bringing GERD Management up to PAR-2.
AB  - Proton pump inhibitors (PPIs) are extremely effective for mucosal healing of
      reflux esophagitis, but less so for relieving the symptom of heartburn. PPIs
      block the secretion of gastric acid, the caustic effects of which have been
      assumed to be the primary culprit in the pathogenesis of reflux esophagitis.
      However, mounting data suggest that reflux-stimulated, immune-mediated mechanisms
      may underlie the development of esophagitis in patients with gastroesophageal
      reflux disease (GERD). Thus, the future of GERD therapy, particularly for
      patients who are refractory to PPIs, may be the targeting of proteins such as
      proteinase-activated receptor-2, which have central roles in the generation of
      immune-mediated esophageal mucosal damage and in eliciting the symptom of
      heartburn.

PMID- 20818354
TI  - Continue or discontinue warfarin for fecal occult blood testing in 2010? Does the
      published evidence provide an answer?
AB  - Whether to continue or discontinue warfarin before fecal occult blood testing
      (FOBT) requires comparison of the risks and benefits of both choices. Clinical
      practice varies on this issue, and guidelines are silent. A small body of
      evidence about the effect of warfarin on test characteristics of FOBT is
      inconclusive, although it suggests no effect. Retrospective studies on this topic
      may be prone to transfer bias, which affects the composition of the groups
      assembled for study. Considering the risks and benefits of discontinuing warfarin
      qualitatively, along with the published literature and clinical context in 2010,
      where tolerance for false-positive results is higher than it used to be and where
      immunochemical FOBT is a better screening test than older, guaiac-based FOBT,
      "no" seems like the "commonsense" answer.

PMID- 20818355
TI  - Capsule endoscopy in suspected Crohn's disease: "yield" does not equal
      "diagnosis".

PMID- 20818357
TI  - Single- vs. double-balloon enteroscopy in patients with small-bowel disorders:
      the jury is still out.

PMID- 20818359
TI  - HBsAg seroclearance and mortality.

PMID- 20818362
TI  - Interferon-gamma may improve differentiation between intestinal tuberculosis and
      Crohn's disease.

PMID- 20818363
TI  - Colonoscopy by non-gastroenterologists: is something better than nothing?

PMID- 20818365
TI  - Diabetes mellitus, obesity, and hepatocellular carcinoma: the jury is still out.

PMID- 20818366
TI  - The "importance of ensuring adequate coagulation function" prior to resection of
      large colon polyps.

PMID- 20818367
TI  - Hepatitis B vaccine administered by intradermal route in patients with celiac
      disease unresponsive to the intramuscular vaccination schedule: a pilot study.

PMID- 20818368
TI  - Insufficiency of electrolyte and fluid secretion by pancreatic ductal cells leads
      to increased patient risk for pancreatitis.

PMID- 20818369
TI  - Endoscopic hemorrhoid ligation is simple, safe, and eff ective. Response to su
      and chiu.

PMID- 20818374
TI  - Oligomeric organization of the B-cell antigen receptor on resting cells.
AB  - B lymphocytes are activated by many different antigens to produce specific
      antibodies protecting higher organisms from infection. To detect its cognate
      antigen, each B cell contains up to 120,000 B-cell antigen receptor (BCR)
      complexes on its cell surface. How these abundant receptors stay silent on
      resting B cells and how they can be activated by a molecularly diverse set of
      ligands is poorly understood. Here we show, with the use of a quantitative
      bifluorescence complementation assay (BiFC), that the BCR has an intrinsic
      ability to form oligomers on the surface of living cells. A BCR mutant that fails
      to form oligomers is more active and cannot be expressed stably on the B-cell
      surface, whereas BiFC-stabilized BCR oligomers are less active and more strongly
      expressed on the surface. We propose that oligomers are the autoinhibited form of
      the BCR and that it is the shift from closed BCR oligomers to clustered monomers
      that drives B-cell activation in a way that is independent of the structural
      input from the antigen.

PMID- 20818375
TI  - Phosphorylation of MLL by ATR is required for execution of mammalian S-phase
      checkpoint.
AB  - Cell cycle checkpoints are implemented to safeguard the genome, avoiding the
      accumulation of genetic errors. Checkpoint loss results in genomic instability
      and contributes to the evolution of cancer. Among G1-, S-, G2- and M-phase
      checkpoints, genetic studies indicate the role of an intact S-phase checkpoint in
      maintaining genome integrity. Although the basic framework of the S-phase
      checkpoint in multicellular organisms has been outlined, the mechanistic details
      remain to be elucidated. Human chromosome-11 band-q23 translocations disrupting
      the MLL gene lead to poor prognostic leukaemias. Here we assign MLL as a novel
      effector in the mammalian S-phase checkpoint network and identify checkpoint
      dysfunction as an underlying mechanism of MLL leukaemias. MLL is phosphorylated
      at serine 516 by ATR in response to genotoxic stress in the S phase, which
      disrupts its interaction with, and hence its degradation by, the SCF(Skp2) E3
      ligase, leading to its accumulation. Stabilized MLL protein accumulates on
      chromatin, methylates histone H3 lysine 4 at late replication origins and
      inhibits the loading of CDC45 to delay DNA replication. Cells deficient in MLL
      showed radioresistant DNA synthesis and chromatid-type genomic abnormalities,
      indicative of S-phase checkpoint dysfunction. Reconstitution of Mll(-/-) (Mll
      also known as Mll1) mouse embryonic fibroblasts with wild-type but not S516A or
      DeltaSET mutant MLL rescues the S-phase checkpoint defects. Moreover, murine
      myeloid progenitor cells carrying an Mll-CBP knock-in allele that mimics human
      t(11;16) leukaemia show a severe radioresistant DNA synthesis phenotype. MLL
      fusions function as dominant negative mutants that abrogate the ATR-mediated
      phosphorylation/stabilization of wild-type MLL on damage to DNA, and thus
      compromise the S-phase checkpoint. Together, our results identify MLL as a key
      constituent of the mammalian DNA damage response pathway and show that
      deregulation of the S-phase checkpoint incurred by MLL translocations probably
      contributes to the pathogenesis of human MLL leukaemias.

PMID- 20818376
TI  - Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a
      pathologic microenvironment.
AB  - We have identified a new role for the matrix enzyme lysyl oxidase-like-2 (LOXL2)
      in the creation and maintenance of the pathologic microenvironment of cancer and
      fibrotic disease. Our analysis of biopsies from human tumors and fibrotic lung
      and liver tissues revealed an increase in LOXL2 in disease-associated stroma and
      limited expression in healthy tissues. Targeting LOXL2 with an inhibitory
      monoclonal antibody (AB0023) was efficacious in both primary and metastatic
      xenograft models of cancer, as well as in liver and lung fibrosis models.
      Inhibition of LOXL2 resulted in a marked reduction in activated fibroblasts,
      desmoplasia and endothelial cells, decreased production of growth factors and
      cytokines and decreased transforming growth factor-beta (TGF-beta) pathway
      signaling. AB0023 outperformed the small-molecule lysyl oxidase inhibitor beta
      aminoproprionitrile. The efficacy and safety of LOXL2-specific AB0023 represents
      a new therapeutic approach with broad applicability in oncologic and fibrotic
      diseases.

PMID- 20818377
TI  - CXCR2 mediates NADPH oxidase-independent neutrophil extracellular trap formation
      in cystic fibrosis airway inflammation.
AB  - Upon activation, neutrophils release DNA fibers decorated with antimicrobial
      proteins, forming neutrophil extracellular traps (NETs). Although NETs are
      bactericidal and contribute to innate host defense, excessive NET formation has
      been linked to the pathogenesis of autoinflammatory diseases. However, the
      mechanisms regulating NET formation, particularly during chronic inflammation,
      are poorly understood. Here we show that the G protein-coupled receptor (GPCR)
      CXCR2 mediates NET formation. Downstream analyses showed that CXCR2-mediated NET
      formation was independent of NADPH oxidase and involved Src family kinases. We
      show the pathophysiological relevance of this mechanism in cystic fibrosis lung
      disease, characterized by chronic neutrophilic inflammation. We found abundant
      NETs in airway fluids of individuals with cystic fibrosis and mouse cystic
      fibrosis lung disease, and NET amounts correlated with impaired obstructive lung
      function. Pulmonary blockade of CXCR2 by intra-airway delivery of small-molecule
      antagonists inhibited NET formation and improved lung function in vivo without
      affecting neutrophil recruitment, proteolytic activity or antibacterial host
      defense. These studies establish CXCR2 as a receptor mediating NADPH oxidase
      independent NET formation and provide evidence that this GPCR pathway is
      operative and druggable in cystic fibrosis lung disease.

PMID- 20818378
TI  - Microbial community resemblance methods differ in their ability to detect
      biologically relevant patterns.
AB  - High-throughput sequencing methods enable characterization of microbial
      communities in a wide range of environments on an unprecedented scale. However,
      insight into microbial community composition is limited by our ability to detect
      patterns in this flood of sequences. Here we compare the performance of 51
      analysis techniques using real and simulated bacterial 16S rRNA pyrosequencing
      datasets containing either clustered samples or samples arrayed across
      environmental gradients. We found that many diversity patterns were evident with
      severely undersampled communities and that methods varied widely in their ability
      to detect gradients and clusters. Chi-squared distances and Pearson correlation
      distances performed especially well for detecting gradients, whereas Gower and
      Canberra distances performed especially well for detecting clusters. These
      results also provide a basis for understanding tradeoffs between number of
      samples and depth of coverage, tradeoffs that are important to consider when
      designing studies to characterize microbial communities.

PMID- 20818379
TI  - Near-infrared fluorescent proteins.
AB  - Fluorescent proteins with emission wavelengths in the near-infrared and infrared
      range are in high demand for whole-body imaging techniques. Here we report near
      infrared dimeric fluorescent proteins eqFP650 and eqFP670. To our knowledge,
      eqFP650 is the brightest fluorescent protein with emission maximum above 635 nm,
      and eqFP670 displays the most red-shifted emission maximum and high
      photostability.

PMID- 20818380
TI  - Monitoring multiple distances within a single molecule using switchable FRET.
AB  - The analysis of structure and dynamics of biomolecules is important for
      understanding their function. Toward this aim, we introduce a method called
      'switchable FRET', which combines single-molecule fluorescence resonance energy
      transfer (FRET) with reversible photoswitching of fluorophores. Typically, single
      molecule FRET is measured within a single donor-acceptor pair and reports on only
      one distance. Although multipair FRET approaches that monitor multiple distances
      have been developed, they are technically challenging and difficult to extend,
      mainly because of their reliance on spectrally distinct acceptors. In contrast,
      switchable FRET sequentially probes FRET between a single donor and spectrally
      identical photoswitchable acceptors, dramatically reducing the experimental and
      analytical complexity and enabling direct monitoring of multiple distances. Our
      experiments on DNA molecules, a protein-DNA complex and dynamic Holliday
      junctions demonstrate the potential of switchable FRET for studying dynamic,
      multicomponent biomolecules.

PMID- 20818381
TI  - A genome-wide association study in the Japanese population identifies
      susceptibility loci for type 2 diabetes at UBE2E2 and C2CD4A-C2CD4B.
AB  - We conducted a genome-wide association study of type 2 diabetes (T2D) using
      459,359 SNPs in a Japanese population with a three-stage study design (stage 1,
      4,470 cases and 3,071 controls; stage 2, 2,886 cases and 3,087 controls; stage 3,
      3,622 cases and 2,356 controls). We identified new associations in UBE2E2 on
      chromosome 3 and in C2CD4A-C2CD4B on chromosome 15 at genome-wide significant
      levels (rs7612463 in UBE2E2, combined P = 2.27 * 10-9; rs7172432 in C2CD4A
      C2CD4B, combined P = 3.66 * 10-9). The association of these two loci with T2D was
      replicated in other east Asian populations. In the European populations, the
      C2CD4A-C2CD4B locus was significantly associated with T2D, and a combined
      analysis of all populations gave P = 8.78 * 10-14, whereas the UBE2E2 locus did
      not show association to T2D. In conclusion, we identified two new loci at UBE2E2
      and C2CD4A-C2CD4B associated with susceptibility to T2D.

PMID- 20818382
TI  - PRDM9 variation strongly influences recombination hot-spot activity and meiotic
      instability in humans.
AB  - PRDM9 has recently been identified as a likely trans regulator of meiotic
      recombination hot spots in humans and mice. PRDM9 contains a zinc finger array
      that, in humans, can recognize a short sequence motif associated with hot spots,
      with binding to this motif possibly triggering hot-spot activity via chromatin
      remodeling. We now report that human genetic variation at the PRDM9 locus has a
      strong effect on sperm hot-spot activity, even at hot spots lacking the sequence
      motif. Subtle changes within the zinc finger array can create hot-spot
      nonactivating or enhancing variants and can even trigger the appearance of a new
      hot spot, suggesting that PRDM9 is a major global regulator of hot spots in
      humans. Variation at the PRDM9 locus also influences aspects of genome
      instability-specifically, a megabase-scale rearrangement underlying two genomic
      disorders as well as minisatellite instability-implicating PRDM9 as a risk factor
      for some pathological genome rearrangements.

PMID- 20818383
TI  - High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in
      human complex I deficiency.
AB  - Discovering the molecular basis of mitochondrial respiratory chain disease is
      challenging given the large number of both mitochondrial and nuclear genes that
      are involved. We report a strategy of focused candidate gene prediction, high
      throughput sequencing and experimental validation to uncover the molecular basis
      of mitochondrial complex I disorders. We created seven pools of DNA from a cohort
      of 103 cases and 42 healthy controls and then performed deep sequencing of 103
      candidate genes to identify 151 rare variants that were predicted to affect
      protein function. We established genetic diagnoses in 13 of 60 previously
      unsolved cases using confirmatory experiments, including cDNA complementation to
      show that mutations in NUBPL and FOXRED1 can cause complex I deficiency. Our
      study illustrates how large-scale sequencing, coupled with functional prediction
      and experimental validation, can be used to identify causal mutations in
      individual cases.

PMID- 20818384
TI  - The effects of electrical microstimulation on cortical signal propagation.
AB  - Electrical stimulation has been used in animals and humans to study potential
      causal links between neural activity and specific cognitive functions. Recently,
      it has found increasing use in electrotherapy and neural prostheses. However, the
      manner in which electrical stimulation-elicited signals propagate in brain
      tissues remains unclear. We used combined electrostimulation, neurophysiology,
      microinjection and functional magnetic resonance imaging (fMRI) to study the
      cortical activity patterns elicited during stimulation of cortical afferents in
      monkeys. We found that stimulation of a site in the lateral geniculate nucleus
      (LGN) increased the fMRI signal in the regions of primary visual cortex (V1) that
      received input from that site, but suppressed it in the retinotopically matched
      regions of extrastriate cortex. Consistent with previous observations,
      intracranial recordings indicated that a short excitatory response occurring
      immediately after a stimulation pulse was followed by a long-lasting inhibition.
      Following microinjections of GABA antagonists in V1, LGN stimulation induced
      positive fMRI signals in all of the cortical areas. Taken together, our findings
      suggest that electrical stimulation disrupts cortico-cortical signal propagation
      by silencing the output of any neocortical area whose afferents are electrically
      stimulated.

PMID- 20818385
TI  - Stress-induced priming of glutamate synapses unmasks associative short-term
      plasticity.
AB  - Exposure to a stressor sensitizes or 'primes' the hypothalamic-pituitary-adrenal
      axis to a subsequent novel stressor. The synaptic mechanisms underlying this
      priming, however, are not known. We found that exposing a rat to a single
      stressor primed glutamate synapses in the paraventricular nucleus of the
      hypothalamus and allowed them to undergo a short-term potentiation (STP)
      following a burst of high-frequency afferent activity. This transient
      potentiation requires a corticotrophin-releasing hormone-dependent depression of
      postsynaptic NMDA receptors (NMDARs). The long-term depression of NMDAR function
      after stress prevented the vesicular release of an inhibitory retrograde
      messenger that, in control conditions, arrests STP. Following stress, STP
      manifested as an increase in the release probability of glutamate that was
      sufficient to induce multivesicular release. Our findings indicate that the
      priming of synapses to express STP is a synaptic correlate to stress-induced
      behavioral and neuroendocrine sensitization.

PMID- 20818387
TI  - A Pumilio-induced RNA structure switch in p27-3' UTR controls miR-221 and miR-222
      accessibility.
AB  - Key regulators of 3' untranslated regions (3' UTRs) are microRNAs and RNA-binding
      proteins (RBPs). The p27 tumour suppressor is highly expressed in quiescent
      cells, and its downregulation is required for cell cycle entry after growth
      factor stimulation. Intriguingly, p27 accumulates in quiescent cells despite high
      levels of its inhibitors miR-221 and miR-222 (Refs 5, 6). Here we show that miR
      221 and miR-222 are underactive towards p27-3' UTR in quiescent cells, as a
      result of target site hindrance. Pumilio-1 (PUM1) is a ubiquitously expressed RBP
      that was shown to interact with p27-3' UTR. In response to growth factor
      stimulation, PUM1 is upregulated and phosphorylated for optimal induction of its
      RNA-binding activity towards the p27-3' UTR. PUM1 binding induces a local change
      in RNA structure that favours association with miR-221 and miR-222, efficient
      suppression of p27 expression, and rapid entry to the cell cycle. We have
      therefore uncovered a novel RBP-induced structural switch modulating microRNA
      mediated gene expression regulation.

PMID- 20818386
TI  - Pet-1 is required across different stages of life to regulate serotonergic
      function.
AB  - Transcriptional cascades are required for the specification of serotonin (5-HT)
      neurons and behaviors modulated by 5-HT. Several cascade factors are expressed
      throughout the lifespan, which suggests that their control of behavior might not
      be temporally restricted to programming normal numbers of 5-HT neurons. We used
      new mouse conditional targeting approaches to investigate the ongoing
      requirements for Pet-1 (also called Fev), a cascade factor that is required for
      the initiation of 5-HT synthesis, but whose expression persists into adulthood.
      We found that Pet-1 was required after the generation of 5-HT neurons for
      multiple steps in 5-HT neuron maturation, including axonal innervation of the
      somatosensory cortex, expression of appropriate firing properties, and the
      expression of the Htr1a and Htr1b autoreceptors. Pet-1 was still required in
      adult 5-HT neurons to preserve normal anxiety-related behaviors through direct
      autoregulated control of serotonergic gene expression. These findings indicate
      that Pet-1 is required across the lifespan of the mouse and that behavioral
      pathogenesis can result from both developmental and adult-onset alterations in
      serotonergic transcription.

PMID- 20818388
TI  - Puma is required for p53-induced depletion of adult stem cells.
AB  - Mammalian ageing is accompanied by accumulation of genomic DNA damage and
      progressive decline in the ability of tissues to regenerate. DNA damage activates
      the tumour suppressor p53, which leads to cell-cycle arrest, senescence or
      apoptosis. The stability and activity of p53 are induced by DNA damage through
      posttranslational modifications such as phosphorylation of Thr 21 and Ser 23
      (refs 2, 3, 4, 5). To investigate the roles of DNA damage and p53 in tissue
      regenerative capability, two phosphorylation-site mutations (T21D and S23D) were
      introduced into the endogenous p53 gene in mice, so that the synthesized protein
      mimics phosphorylated p53. The knock-in mice exhibit constitutive p53 activation
      and segmental progeria that is correlated with the depletion of adult stem cells
      in multiple tissues, including bone marrow, brain and testes. Furthermore, a
      deficiency of Puma, which is required for p53-dependent apoptosis after DNA
      damage, rescues segmental progeria and prevents the depletion of adult stem
      cells. These findings suggest a key role of p53-dependent apoptosis in depleting
      adult stem cells after the accumulation of DNA damage, which leads to a decrease
      in tissue regeneration.

PMID- 20818389
TI  - Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition.
AB  - The epithelial-mesenchymal transition (EMT), one of the main mechanisms
      underlying development of cancer metastasis, induces stem-like properties in
      epithelial cells. Bmi1 is a polycomb-group protein that maintains self-renewal,
      and is frequently overexpressed in human cancers. Here, we show the direct
      regulation of BMI1 by the EMT regulator, Twist1. Furthermore, Twist1 and Bmi1
      were mutually essential to promote EMT and tumour-initiating capability. Twist1
      and Bmi1 act cooperatively to repress expression of both E-cadherin and p16INK4a.
      In patients with head and neck cancers, increased levels of both Twist1 and Bmi1
      correlated with downregulation of E-cadherin and p16INK4a, and was associated
      with the worst prognosis. These results suggest that Twist1-induced EMT and
      tumour-initiating capability in cancer cells occurs through chromatin
      remodelling, which leads to unfavourable clinical outcomes.

PMID- 20818390
TI  - A metazoan ortholog of SpoT hydrolyzes ppGpp and functions in starvation
      responses.
AB  - In nutrient-starved bacteria, RelA and SpoT proteins have key roles in reducing
      cell growth and overcoming stresses. Here we identify functional SpoT orthologs
      in metazoa (named Mesh1, encoded by HDDC3 in human and Q9VAM9 in Drosophila
      melanogaster) and reveal their structures and functions. Like the bacterial
      enzyme, Mesh1 proteins contain an active site for ppGpp hydrolysis and a
      conserved His-Asp-box motif for Mn(2+) binding. Consistent with these structural
      data, Mesh1 efficiently catalyzes hydrolysis of guanosine 3',5'-diphosphate
      (ppGpp) both in vitro and in vivo. Mesh1 also suppresses SpoT-deficient lethality
      and RelA-induced delayed cell growth in bacteria. Notably, deletion of Mesh1
      (Q9VAM9) in Drosophila induces retarded body growth and impaired starvation
      resistance. Microarray analyses reveal that the amino acid-starved Mesh1 null
      mutant has highly downregulated DNA and protein synthesis-related genes and
      upregulated stress-responsible genes. These data suggest that metazoan SpoT
      orthologs have an evolutionarily conserved function in starvation responses.

PMID- 20818391
TI  - Uniform transitions of the general RNA polymerase II transcription complex.
AB  - We present genome-wide occupancy profiles for RNA polymerase (Pol) II, its
      phosphorylated forms and transcription factors in proliferating yeast. Pol II
      exchanges initiation factors for elongation factors during a 5' transition that
      is completed 150 nucleotides downstream of the transcription start site (TSS).
      The resulting elongation complex is composed of all the elongation factors and
      shows high levels of Ser7 and Ser5 phosphorylation on the C-terminal repeat
      domain (CTD) of Pol II. Ser2 phosphorylation levels increase until 600-1,000
      nucleotides downstream of the TSS and do not correlate with recruitment of Spt6
      and Pcf11, which bind the Ser2-phosphorylated CTD in vitro. This indicates CTD
      independent recruitment mechanisms and CTD masking in vivo. Elongation complexes
      are productive and disassemble in a two-step 3' transition. Paf1, Spt16 (part of
      the FACT complex), and the CTD kinases Bur1 and Ctk1 exit upstream of the
      polyadenylation site, whereas Spt4, Spt5, Spt6, Spn1 (also called Iws1) and Elf1
      exit downstream. Transitions are uniform and independent of gene length, type and
      expression.

PMID- 20818392
TI  - The exon junction complex differentially marks spliced junctions.
AB  - The exon junction complex (EJC), which is deposited onto mRNAs as a consequence
      of splicing, is involved in multiple post-transcriptional events in metazoa.
      Here, using Drosophila melanogaster cells, we show that only some introns trigger
      EJC-dependent nonsense-mediated mRNA decay and that EJC association with
      particular spliced junctions depends on RNA cis-acting sequences. This study
      provides the first evidence to our knowledge that EJC deposition is not
      constitutive but instead is a regulated process.

PMID- 20818393
TI  - Cooperative interaction of transcription termination factors with the RNA
      polymerase II C-terminal domain.
AB  - Phosphorylation of the C-terminal domain (CTD) of RNA polymerase II controls the
      co-transcriptional assembly of RNA processing and transcription factors.
      Recruitment relies on conserved CTD-interacting domains (CIDs) that recognize
      different CTD phosphoisoforms during the transcription cycle, but the molecular
      basis for their specificity remains unclear. We show that the CIDs of two
      transcription termination factors, Rtt103 and Pcf11, achieve high affinity and
      specificity both by specifically recognizing the phosphorylated CTD and by
      cooperatively binding to neighboring CTD repeats. Single-residue mutations at the
      protein-protein interface abolish cooperativity and affect recruitment at the 3'
      end processing site in vivo. We suggest that this cooperativity provides a signal
      response mechanism to ensure that its action is confined only to proper
      polyadenylation sites where Ser2 phosphorylation density is highest.

PMID- 20818394
TI  - Shared dependence on the DNA-binding factor TOX for the development of lymphoid
      tissue-inducer cell and NK cell lineages.
AB  - TOX is a DNA-binding factor required for development of CD4(+) T cells, natural
      killer T cells and regulatory T cells. Here we document that both natural killer
      (NK) cell development and lymphoid tissue organogenesis were also inhibited in
      the absence of TOX. We found that the development of lymphoid tissue-inducer
      cells, a rare subset of specialized cells that has an integral role in lymphoid
      tissue organogenesis, required TOX. Tox was upregulated considerably in immature
      NK cells in the bone marrow, consistent with the loss of mature NK cells in the
      absence of this nuclear protein. Thus, many cell lineages of the immune system
      share a TOX-dependent step for development.

PMID- 20818395
TI  - Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I.
AB  - Caspase-12 has been shown to negatively modulate inflammasome signaling during
      bacterial infection. Its function in viral immunity, however, has not been
      characterized. We now report an important role for caspase-12 in controlling
      viral infection via the pattern-recognition receptor RIG-I. After challenge with
      West Nile virus (WNV), caspase-12-deficient mice had greater mortality, higher
      viral burden and defective type I interferon response compared with those of
      challenged wild-type mice. In vitro studies of primary neurons and mouse
      embryonic fibroblasts showed that caspase-12 positively modulated the production
      of type I interferon by regulating E3 ubiquitin ligase TRIM25-mediated
      ubiquitination of RIG-I, a critical signaling event for the type I interferon
      response to WNV and other important viral pathogens.

PMID- 20818396
TI  - SLAM is a microbial sensor that regulates bacterial phagosome functions in
      macrophages.
AB  - Phagocytosis is a pivotal process by which macrophages eliminate microorganisms
      after recognition by pathogen sensors. Here we unexpectedly found that the self
      ligand and cell surface receptor SLAM functioned not only as a costimulatory
      molecule but also as a microbial sensor that controlled the killing of gram
      negative bacteria by macrophages. SLAM regulated activity of the NADPH oxidase
      NOX2 complex and phagolysosomal maturation after entering the phagosome,
      following interaction with the bacterial outer membrane proteins OmpC and OmpF.
      SLAM recruited a complex containing the intracellular class III
      phosphatidylinositol kinase Vps34, its regulatory protein kinase Vps15 and the
      autophagy-associated molecule beclin-1 to the phagosome, which was responsible
      for inducing the accumulation of phosphatidylinositol-3-phosphate, a regulator of
      both NOX2 function and phagosomal or endosomal fusion. Thus, SLAM connects the
      gram-negative bacterial phagosome to ubiquitous cellular machinery responsible
      for the control of bacterial killing.

PMID- 20818397
TI  - A small-molecule screen identifies new functions for the plant hormone
      strigolactone.
AB  - Parasitic weeds of the genera Striga and Orobanche are considered the most
      damaging agricultural agents in the developing world. An essential step in
      parasitic seed germination is sensing a group of structurally related compounds
      called strigolactones that are released by host plants. Although this makes
      strigolactone synthesis and action a major target of biotechnology, little
      fundamental information is known about this hormone. Chemical genetic screening
      using Arabidopsis thaliana as a platform identified a collection of related small
      molecules, cotylimides, which perturb strigolactone accumulation. Suppressor
      screens against select cotylimides identified light-signaling genes as positive
      regulators of strigolactone levels. Molecular analysis showed strigolactones
      regulate the nuclear localization of the COP1 ubiquitin ligase, which in part
      determines the levels of light regulators such as HY5. This information not only
      uncovers new functions for strigolactones but was also used to identify rice
      cultivars with reduced capacity to germinate parasitic seed.

PMID- 20818398
TI  - Non-dipping pattern of hypertension and obstructive sleep apnea syndrome.
AB  - There is growing recognition of cardiovascular consequences of obstructive sleep
      apnea (OSA). Recurrent episodes of airway obstructions result in hypoxia and
      hypercapnia increasing sympathetic neural tone, which in turn causes
      vasoconstriction and marked increases in blood pressure (BP). BP response to OSA
      may be important in understanding the absence of nocturnal BP fall in the
      subgroup of hypertensive patients termed 'non-dippers'. Even mild sleep apnea can
      increase nocturnal BP through different mechanisms including hypoxemia,
      sympathetic activation, mechanical changes and disruption of normal sleep. Sleep
      apnea may be an important factor in determining the increased cardiovascular risk
      in hypertensive non-dippers. Effective treatment of sleep apnea may attenuate
      neurohumoral and metabolic abnormalities, improve diurnal BP control and
      conceivably reduce cardiovascular risk. This review examines the evidence linking
      OSA to non-dipping pattern of hypertension, and discusses potential mechanisms
      underlying this link. We will review first, prognostic value of nighttime BP;
      second, the cardiovascular consequences of sleep apnea; third, the evidence for
      altered diurnal BP profile in sleep apnea; fourth, the mechanisms contributing to
      both nocturnal and daytime hypertension in sleep apnea; fifth, the benefits of
      sleep apnea treatment and finally implications for hypertension management.

PMID- 20818401
TI  - Does erectile dysfunction drug use contribute to risky sexual behavior?

PMID- 20818403
TI  - Image rights and wrongs.

PMID- 20818402
TI  - Treatment satisfaction after 1 year high-power potassium-titanyl-phosphate
      photoselective vaporization of the prostate.
AB  - To investigate the factors that influence treatment satisfaction after high-power
      potassium-titanyl-phosphate (KTP) laser vaporization of the prostate, we compared
      the characteristics between patients who were satisfied and those who were not
      satisfied. In all, 97 patients aged between 53-82 years (median age 67 years)
      underwent high-power KTP laser vaporization of the prostate for lower urinary
      tract symptoms due to benign prostatic hyperplasia. At 12 months postoperatively,
      60 patients were satisfied with the treatment, whereas 37 were dissatisfied.
      Although there were no differences in International Prostate Symptom Score (IPSS)
      values at baseline, the satisfied group scored better in total IPSS at 1, 3, 6,
      and 12 months postoperatively (P < 0.05). At baseline, the maximum flow rate
      (Qmax) was lower in the dissatisfied group and remained low throughout the follow
      up period, with the exception of 1 month postoperatively (P < 0.05), compared
      with the satisfied group. There were no differences in other objective data
      between the two groups, including post-void residual and the number of voids
      based on the frequency-volume charts. In a multivariate model, a higher bladder
      contractility index was associated with a greater likelihood of treatment
      satisfaction 12 months after high-power KTP laser vaporization (odds ratio 1.024,
      95% confidence interval 1.001-1.048, P < 0.05). Patients who were not satisfied
      following the surgery had a smaller improvement in subjective symptoms and
      Q(max). In addition, our findings suggest that the relative risk of treatment
      dissatisfaction following high-power KTP laser vaporization was increased in
      patients with weak detrusor contractility.

PMID- 20818405
TI  - Nanolithography: Written with light.

PMID- 20818406
TI  - Bioimaging: Hot nanoparticles light up cancer.

PMID- 20818407
TI  - Nanobiotechnology: Scaling up synthetic gene circuits.

PMID- 20818408
TI  - Bionanoscience: Nano meets bio at the interface.

PMID- 20818409
TI  - RNA nanotechnology: inspired by DNA.

PMID- 20818411
TI  - Cellular & Molecular Immunology receives its first Impact Factor.

PMID- 20818410
TI  - In vivo exploration of the functional activity of the non-coding 8q24 prostate
      cancer risk locus.

PMID- 20818412
TI  - Contribution of functional KIR3DL1 to ankylosing spondylitis.
AB  - Increasing evidence points to a role for killer immunoglobulin-like receptors
      (KIRs) in the development of autoimmune diseases. In particular, a positive
      association of KIR3DS1 (activating receptor) and a negative association of
      KIR3DL1 (inhibitory receptor) alleles with ankylosing spondylitis (AS) have been
      reported by several groups. However, none of the studies analyzed these
      associations in the context of functionality of polymorphic KIR3DL1. To better
      understand how the KIR3DL1/3DS1 genes determine susceptibility to AS, we analyzed
      the frequencies of alleles and genotypes encoding functional (KIR3DL1*F) and non
      functional (KIR3DL1*004) receptors. We genotyped 83 AS patients and 107 human
      leukocyte antigen (HLA)-B27-positive healthy controls from the Russian Caucasian
      population using a two-stage sequence-specific primer PCR, which distinguishes
      KIR3DS1, KIR3DL1*F and KIR3DL1*004 alleles. For the patients carrying two
      functional KIR3DL1 alleles, those alleles were additionally genotyped to identify
      KIR3DL1*005 and KIR3DL1*007 alleles, which are functional but are expressed at
      low levels. KIR3DL1 was negatively associated with AS at the expense of KIR3DL1*F
      but not of KIR3DL1*004. This finding indicates that the inhibitory KIR3DL1
      receptor protects against the development of AS and is not simply a passive
      counterpart of the segregating KIR3DS1 allele encoding the activating receptor.
      However, analysis of genotype frequencies indicates that the presence of KIR3DS1
      is a more important factor for AS susceptibility than the absence of KIR3DL1*F.
      The activation of either natural killer (NK) or T cells via the KIR3DS1 receptor
      can be one of the critical events in AS development, while the presence of the
      functional KIR3DL1 receptor has a protective effect. Nevertheless, even
      individuals with a genotype that carried two inhibitory KIR3DL1 alleles expressed
      at high levels could develop AS.

PMID- 20818413
TI  - Current perspectives of natural killer cell education by MHC class I molecules.
AB  - From the early days of natural killer (NK) cell research, it was clear that MHC
      genes controlled the specificity of mouse NK cell-dependent responses, such as
      the ability to reject transplanted allogeneic bone marrow and to kill tumour
      cells. Although several mechanisms that are involved in this 'education' process
      have been clarified, most of the mechanisms have still to be identified. Here, we
      review the current understanding of the processes that are involved in NK cell
      education, including how the host MHC class I molecules regulate responsiveness
      and receptor repertoire formation in NK cells and the signalling pathways that
      are involved.

PMID- 20818414
TI  - Evolution of diverse cell division and vesicle formation systems in Archaea.
AB  - Recently a novel cell division system comprised of homologues of eukaryotic ESCRT
      III (endosomal sorting complex required for transport III) proteins was
      discovered in the hyperthermophilic crenarchaeote Sulfolobus acidocaldarius. On
      the basis of this discovery, we undertook a comparative genomic analysis of the
      machineries for cell division and vesicle formation in Archaea. Archaea possess
      at least three distinct membrane remodelling systems: the FtsZ-based bacterial
      type system, the ESCRT-III-based eukaryote-like system and a putative novel
      system that uses an archaeal actin-related protein. Many archaeal genomes encode
      assortments of components from different systems. Evolutionary reconstruction
      from these findings suggests that the last common ancestor of the extant Archaea
      possessed a complex membrane remodelling apparatus, different components of which
      were lost during subsequent evolution of archaeal lineages. By contrast,
      eukaryotes seem to have inherited all three ancestral systems.

PMID- 20818416
TI  - The orphan G protein-coupled receptor GPR55 promotes cancer cell proliferation
      via ERK.
AB  - GPR55 is an orphan G protein-coupled receptor that may be engaged by some lipid
      ligands such as lysophosphatidylinositol and cannabinoid-type compounds. Very
      little is known about its expression pattern and physio-pathological relevance,
      and its pharmacology and signaling are still rather controversial. Here we
      analyzed the expression and function of GPR55 in cancer cells. Our data show that
      GPR55 expression in human tumors from different origins correlates with their
      aggressiveness. Moreover, GPR55 promotes cancer cell proliferation, both in cell
      cultures and in xenografted mice, through the overactivation of the extracellular
      signal-regulated kinase cascade. These findings reveal the importance of GPR55 in
      human cancer, and suggest that it could constitute a new biomarker and
      therapeutic target in oncology.

PMID- 20818415
TI  - Interactions between bacterial pathogens and mitochondrial cell death pathways.
AB  - The modulation of host cell death pathways by bacteria has been recognized as a
      major pathogenicity mechanism. Among other strategies, bacterial pathogens can
      hijack the cell death machinery of host cells by influencing the signalling
      pathways that converge on the mitochondria. In particular, many bacterial
      proteins have evolved to interact in a highly specific manner with host
      mitochondria, thereby modulating the decision between cell life and death. In
      this Review, we explore the intimate interactions between bacterial pathogens and
      mitochondrial cell death pathways.

PMID- 20818417
TI  - Control of mammary tumor differentiation by SKI-606 (bosutinib).
AB  - C-Src is infrequently mutated in human cancers but it mediates oncogenic signals
      of many activated growth factor receptors and thus remains a key target for
      cancer therapy. However, the broad function of Src in many cell types and
      processes requires evaluation of Src-targeted therapeutics within a normal
      developmental and immune-competent environment. In an effort to understand the
      appropriate clinical use of Src inhibitors, we tested an Src inhibitor, SKI-606
      (bosutinib), in the MMTV-PyVmT transgenic mouse model of breast cancer. Tumor
      formation in this model is dependent on the presence of Src, but the necessity of
      Src kinase activity for tumor formation has not been determined. Furthermore, Src
      inhibitors have not been examined in an autochthonous tumor model that permits
      assessment of effects on different stages of tumor progression. Here we show that
      oral administration of SKI-606 inhibited the phosphorylation of Src in mammary
      tumors and caused a rapid decrease in the Ezh2 Polycomb group histone H3K27
      methyltransferase and an increase in epithelial organization. SKI-606 prevented
      the appearance of palpable tumors in over 50% of the animals and stopped tumor
      growth in older animals with pre-existing tumors. These antitumor effects were
      accompanied by decreased cellular proliferation, altered tumor blood vessel
      organization and dramatically increased differentiation to lactational and
      epidermal cell fates. SKI-606 controls the development of mammary tumors by
      inducing differentiation.

PMID- 20818418
TI  - Harnessing the complexity of DNA-damage response pathways to improve cancer
      treatment outcomes.
AB  - The DNA-damage response (DDR) pathways consist of interconnected components that
      respond to DNA damage to allow repair and promote cell survival. The DNA repair
      pathways and downstream cellular responses have diverged in cancer cells compared
      with normal cells because of genetic alterations that underlie drug resistance,
      disabled repair and resistance to apoptosis. Consequently, abrogating DDR
      pathways represents an important mechanism for enhancing the therapeutic index of
      DNA-damaging anticancer agents. In this review, we discuss the DDR pathways that
      determine antitumor effects of DNA-damaging agents with a specific focus on
      treatment outcomes in tumors carrying a defective p53 pathway. Finely tuned
      survival and death pathways govern the cellular responses downstream of the
      cytotoxic insults inherent in anticancer treatment. The significance and relative
      contributions of cellular responses including apoptosis, mitotic catastrophe and
      senescence are discussed in relation to the web of molecular interactions that
      affect such outcomes. We propose that promising combinations of DNA-damaging
      anticancer treatments with DDR-pathway inhibition would be further enhanced by
      activating downstream apoptotic pathways. The proposed rationale ensures that
      actual cell death is the preferred outcome of cancer treatment instead of other
      responses, including reversible cell cycle arrest, autophagy or senescence.
      Finally, to better measure the contribution of different cellular responses to
      anticancer treatments, multiplex in vivo assessments of therapy-induced response
      pathways such as cell death, senescence and mitotic catastrophe is desirable
      rather than the current reliance on the measurement of a single response pathway
      such as apoptosis.

PMID- 20818419
TI  - PRIMA-1(MET)/APR-246 targets mutant forms of p53 family members p63 and p73.
AB  - The low molecular weight compound PRIMA-1 and the structural analog PRIMA-1(MET),
      also named APR-246, reactivate mutant p53 through covalent binding to the core
      domain and induce apoptosis in tumor cells. Here, we asked whether PRIMA
      1(MET)/APR-246 can rescue mutant forms of the p53 family members p63 and p73 that
      share high sequence homology with p53. We found that PRIMA-1(MET)/APR-246 can
      restore the pro-apoptotic function to mutant TAp63gamma and TAp73beta in tumor
      cells but has less effect on TAp73alpha. Moreover, PRIMA-1(MET)/APR-246
      stimulated DNA binding of mutant TAp63gamma and induced expression of the
      p53/p63/p73 downstream targets p21 and Noxa. The reactivation of mutant p53, p63
      and p73 by PRIMA-1(MET)/APR-246 indicates a common mechanism, presumably
      involving homologous structural elements in the p53 family proteins. Our findings
      may open avenues for therapeutic intervention in human developmental disorders
      with mutations in p63.

PMID- 20818420
TI  - 4-Methylnitrosamino-1-3-pyridyl-1-butanone (NNK) promotes lung cancer cell
      survival by stimulating thromboxane A2 and its receptor.
AB  - The role of thromboxane A(2) (TxA(2)) in smoking-associated lung cancer is poorly
      understood. This study was conducted to study the role of TxA(2) in smoking
      carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-promoted cell
      survival and growth in human lung cancer cells. We found that NNK increased
      TxA(2) synthase (TxAS) expression and thromboxane B(2) (TxB(2)) generation in
      cultured lung cancer cells, the result of which was supported by the increased
      level of TxAS in lung cancer tissues of smokers. Both TxAS-specific inhibitor
      furegrelate and TxA(2) receptor antagonist SQ29548 completely blocked NNK
      mediated cell survival and growth via inducting apoptosis. TxA(2) receptor
      agonist U46619 reconstituted a near-full survival and growth response to NNK when
      TxAS was inhibited, affirming the role of TxA(2) receptor in NNK-mediated cell
      survival and growth. Suppression of cyclic adenosine monophosphate response
      element binding protein (CREB) activity by its small interference RNA blocked the
      effect of NNK. Phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal
      regulated kinase (ERK) also had a positive role. Altogether, our results have
      revealed that NNK stimulates TxA(2) synthesis and activates its receptor in lung
      cancer cells. The increased TxA(2) may then activate CREB through PI3K/Akt and
      extracellular ERK pathways, thereby contributing to the NNK-promoted survival and
      growth of lung cancer cells.

PMID- 20818421
TI  - Epithelial Hic-5/ARA55 expression contributes to prostate tumorigenesis and
      castrate responsiveness.
AB  - Stromal-epithelial interactions dictate prostate tumorigenesis and response to
      castration. Hydrogen peroxide-inducible clone 5 (Hic-5/ARA55) is a transforming
      growth factor-beta (TGF-beta)-induced coactivator of androgen receptor (AR)
      expressed in the prostate stroma. Interestingly, following castration, we
      identified epithelial expression of Hic-5/ARA55 in mouse and human prostate
      tissues. To determine the role of epithelial Hic-5 in prostate cancer progression
      and castration responsiveness, we compared LNCaP cells having Hic-5 stably
      expressed with the parental LNCaP cells following tissue recombination xenografts
      with mouse prostate stromal cells. We previously identified knocking out prostate
      stromal TGF-beta signaling potentiated castrate-resistant prostate tumors, in a
      Wnt-dependent manner. The LNCaP chimeric tumors containing prostate fibroblasts
      conditionally knocked out for the TGF-beta type II receptor (Tgfbr2-KO) resulted
      in larger, more invasive, and castration-resistant tumors compared those with
      floxed (control) stromal cells. However, the LNCaP-Hic5 associated with Tgfbr2-KO
      fibroblasts generated chimeric tumors with reduced tumor volume, lack of invasion
      and restored castration dependence. Neutralization of canonical Wnt signaling is
      shown to reduce prostate tumor size and restore regression following castration.
      Thus, we hypothesized that epithelial Hic-5/ARA55 expression negatively regulated
      Wnt signaling. The mechanism of the Hic-5/ARA55 effects on castration was
      determined by analysis of the c-myc promoter. C-myc luciferase reporter activity
      suggested Hic-5/ARA55 expression inhibited c-myc activity by beta-catenin.
      Sequential ChIP analysis indicated beta-catenin and T-cell-specific 4 (TCF4)
      bound the endogenous c-myc promoter in the absence of Hic-5 expression. However,
      the formation of a TCF4/Hic-5 repressor complex inhibited c-myc promoter
      activity, by excluding beta-catenin binding with TCF4 on the promoter. The data
      indicate Hic-5/ARA55 expression in response to castration-enabled epithelial
      regression through the repression of c-myc gene at the chromatin level.

PMID- 20818422
TI  - Interfering with RAS-effector protein interactions prevent RAS-dependent tumour
      initiation and causes stop-start control of cancer growth.
AB  - RAS mutations are the most common gain-of-function change in human cancer and
      promise to be a critical therapy target. As a new approach, we have used a
      surrogate to drug the 'undruggable' (that is, RAS-effector protein-protein
      interactions inside cancer cells) in pre-clinical mouse models of RAS-dependent
      cancers. Using this novel reagent, we have specifically targeted RAS signalling
      in a transgenic mouse model of lung cancer by directly blockading RAS-effector
      interactions with an antibody fragment that binds to activated RAS, and show that
      the interaction of RAS and effectors, such as phosphoinositide 3-kinase and RAF,
      is necessary for tumour initiation. Further, interference with oncogenic RAS
      effector interactions result in control of tumour growth in human cancer cells
      but, crucially, does not necessarily cause tumour regression. These findings
      support the concept that ablating RAS-dependent signalling in cancer will have
      chemo-preventive effects that confer a chronic state in cancer and suggest that
      mutant RAS-targeted therapies may require conjoint targeting of other molecules
      and/or current cancer therapeutic strategies (for example, radiotherapy and
      chemotherapy) to be curative. In this context, our findings suggest that the
      oncogene addiction model is not universally correct in its central thesis that
      cancer cell death is inevitable after loss of oncogenic protein function.

PMID- 20818423
TI  - The RNA helicase p68 modulates expression and function of the Delta133 isoform(s)
      of p53, and is inversely associated with Delta133p53 expression in breast cancer.
AB  - The RNA helicase p68 is a potent co-activator of p53-dependent transcription in
      response to DNA damage. Previous independent studies have indicated that p68 and
      the Delta133p53 isoforms, which modulate the function of full-length p53, are
      aberrantly expressed in breast cancers. Here we identify a striking inverse
      association of p68 and Delta133p53 expression in primary breast cancers.
      Consistent with these findings, small interfering RNA depletion of p68 in cell
      lines results in a p53-dependant increase of Delta133p53 in response to DNA
      damage, suggesting that increased Delta133p53 expression could result from
      downregulation of p68 and provide a potential mechanistic explanation for our
      observations in breast cancer. Delta133p53alpha, which has been shown to
      negatively regulate the function of full-length p53, reciprocally inhibits the
      ability of p68 to stimulate p53-dependent transcription from the p21 promoter,
      suggesting that Delta133p53alpha may be competing with p68 to regulate p53
      function. This hypothesis is underscored by our observations that p68 interacts
      with the C-terminal domain of p53, co-immunoprecipitates 133p53alpha from cell
      extracts and interacts only with p53 molecules that are able to form tetramers.
      These data suggest that p68, p53 and 133p53alpha may form part of a complex
      feedback mechanism to regulate the expression of Delta133p53, with consequent
      modification of p53-mediated transcription, and may modulate the function of p53
      in breast and other cancers that harbour wild-type p53.

PMID- 20818424
TI  - Rheb activates AMPK and reduces p27Kip1 levels in Tsc2-null cells via mTORC1
      independent mechanisms: implications for cell proliferation and tumorigenesis.
AB  - Tuberous sclerosis complex (TSC) is an autosomally inherited disorder that causes
      tumors to form in many organs. It is frequently caused by inactivating mutations
      in the TSC2 tumor-suppressor gene. TSC2 negatively regulates the activity of the
      GTPase Rheb and thereby inhibits mammalian target of rapamycin complex 1 (mTORC1)
      signaling. Activation of mTORC1 as a result of lack of TSC2 function is observed
      in TSC and sporadic lymphangioleiomyomatosis (LAM). TSC2 deficiency has recently
      been associated with elevated AMP-activated protein kinase (AMPK) activity, which
      in turn correlated with cytoplasmic localization of p27Kip1 (p27), a negative
      regulator of cyclin-dependent kinase 2 (Cdk2). How AMPK in the absence of TSC2 is
      stimulated is not fully understood. In this study, we demonstrate that Rheb
      activates AMPK and reduces p27 levels in Tsc2-null cells. Importantly, both
      effects occur largely independent of mTORC1. Furthermore, increased p27 levels
      following Rheb depletion correlated with reduced Cdk2 activity and cell
      proliferation in vitro, and with inhibition of tumor formation by Tsc2-null cells
      in vivo. Taken together, our data suggest that Rheb controls proliferation of
      TSC2-deficient cells by a mechanism that involves regulation of AMPK and p27, and
      that Rheb is a potential target for TSC/LAM therapy.

PMID- 20818425
TI  - The immune response to sporadic colorectal cancer in a novel mouse model.
AB  - Current mouse models do not reflect the sporadic nature of colon cancer and do
      not allow the analysis of antitumor immune response because of the lack of known
      tumor-specific antigens. Two transgenic mouse models with spontaneous tumor
      development were generated, directing the expression of SV40T antigen (Tag)
      either constitutively (Vil-Cre * LoxP-Tag-transgenic mice) or stochastically (Vil
      Cre-ER(T2) * LoxP-Tag-transgenic mice) into the putative stem cell region of the
      crypt of Lieberkuhn. Tumor development and antitumor immune response were
      monitored. Vil-Cre * LoxP-Tag mice developed multiple adenocarcinomas of the
      small intestine and colon at an average age of 6 months. During the tumor
      development, Tag-specific immunoglobulin G (IgG) antibodies were induced in half
      of the mice, although they had developed neonatal cytotoxic T lymphocyte (CTL)
      tolerance. This model shows similarity to hereditary colon cancer but not to the
      sporadic tumor development. Therefore, the conditional Vil-Cre-ER(T2) * LoxP-Tag
      mice were established, in which expression of the dormant Tag was induced by
      stochastic, tissue-specific activation of Cre recombinase. These mice
      spontaneously developed highly invasive, metastasizing colon carcinomas at an
      average age of 20 months. Colon carcinomas expressed epithelial and/or
      neuroendocrine markers depending on the grade of differentiation. Young Vil-Cre
      ER(T2) * LoxP-Tag mice had retained CTL responses against epitope IV of Tag. The
      tumors induced strong anti-Tag IgG responses. We report, for the first time, a
      mouse model based on stochastic, tissue-specific activation of a dormant oncogene
      in the colon allowing the analysis of antitumor immune response against primary
      colorectal cancer.

PMID- 20818426
TI  - miR-145-dependent targeting of junctional adhesion molecule A and modulation of
      fascin expression are associated with reduced breast cancer cell motility and
      invasiveness.
AB  - Micro RNAs are small non-coding RNAs, which regulate fundamental cellular and
      developmental processes at the transcriptional and translational level. In breast
      cancer, miR-145 expression is downregulated compared with healthy control tissue.
      As several predicted targets of miR-145 potentially regulate cell motility, we
      aimed at investigating a potential role for miR-145 in breast cancer cell
      motility and invasiveness. Assisted by Affymetrix array technology, we
      demonstrate that overexpression of miR-145 in MDA-MB-231, MCF-7, MDA-MB-468 and
      SK-BR-3 breast cancer cells and in Ishikawa endometrial carcinoma cells leads to
      a downregulation of the cell-cell adhesion protein JAM-A and of the actin
      bundling protein fascin. Moreover, podocalyxin and Serpin E1 mRNA levels were
      downregulated, and gamma-actin, transgelin and MYL9 were upregulated upon miR-145
      overexpression. These miR-145-dependent expression changes drastically decreased
      cancer cell motility, as revealed by time-lapse video microscopy, scratch wound
      closure assays and matrigel invasion assays. Immunofluorescence microscopy
      demonstrated restructuring of the actin cytoskeleton and a change in cell
      morphology by miR-145 overexpression, resulting in a more cortical actin
      distribution, and reduced actin stress fiber and filopodia formation. Nuclear
      rotation was observed in 10% of the pre-miR-145 transfected MDA-MB-231 cells,
      accompanied by a reduction of perinuclear actin. Luciferase activation assays
      confirmed direct miR-145-dependent regulation of the 3'UTR of JAM-A, whereas
      siRNA-mediated knockdown of JAM-A expression resulted in decreased motility and
      invasiveness of MDA-MB-231 and MCF-7 breast cancer cells. Our data identify JAM-A
      and fascin as novel targets of miR-145, firmly establishing a role for miR-145 in
      modulating breast cancer cell motility. Our data provide a rationale for future
      miR-145-targeted approaches of antimetastatic cancer therapy.

PMID- 20818427
TI  - Regulation of C/EBPbeta1 by Ras in mammary epithelial cells and the role of
      C/EBPbeta1 in oncogene-induced senescence.
AB  - Overexpression of Ras(V12) in MCF10A cells, an immortalized mammary epithelial
      cell line, leads to transformation of these cells. We demonstrate that this is
      accompanied by degradation of C/EBPbeta1. C/EBPbeta is a transcription factor in
      which three protein isoforms exist because of alternative translation at three in
      frame methionines. When C/EBPbeta1 is expressed in MCF10A-Ras(V12) cells,
      immunoblot analysis reveals that C/EBPbeta1 is degraded in these cells. Treatment
      of MCF10A-Ras(V12)-C/EBPbeta1 cells with the cdk inhibitor roscovitine leads to
      stabilization of C/EBPbeta1. It has been previously shown that cdk2
      phosphorylates C/EBPbeta on Thr235. We demonstrate that mutation of Thr235 to
      alanine in C/EBPbeta1 is sufficient to restore the stability of C/EBPbeta1
      expression in MCF10A-Ras(V12) cells. Overexpression of Ras(V12) in primary cells
      induces senescence rather than transformation, thus suppressing tumorigenesis.
      C/EBPbeta is required for Ras(V12)-induced senescence in primary mouse embryonic
      fibroblasts. Upregulation of interleukin-6 (IL6) by C/EBPbeta has been shown to
      be necessary for oncogene-induced senescence, but the specific isoform of
      C/EBPbeta has not been investigated. We show that the C/EBPbeta1 isoform
      upregulates IL6 when introduced into normal fibroblasts. In addition, we show
      that C/EBPbeta1 induces senescence. Taken together, degradation of C/EBPbeta1 by
      Ras activation may represent a mechanism to bypass OIS.

PMID- 20818428
TI  - beta-Catenin activation synergizes with PTEN loss to cause bladder cancer
      formation.
AB  - Although deregulation of the Wnt signalling pathway has been implicated in
      urothelial cell carcinoma (UCC), the functional significance is unknown. To test
      its importance, we have targeted expression of an activated form of beta-catenin
      to the urothelium of transgenic mice using Cre-Lox technology (UroIICRE(+) beta
      catenin(exon3/+)). Expression of this activated form of beta-catenin led to the
      formation of localized hyperproliferative lesions by 3 months, which did not
      progress to malignancy. These lesions were characterized by a marked increase of
      the phosphatase and tensin homologue (PTEN) tumour suppressor protein. This
      appears to be a direct consequence of activating Wnt signalling in the bladder as
      conditional deletion of the adenomatous polyposis coli (Apc) gene within the
      adult bladder led rapidly to coincident beta-catenin and PTEN expression. This
      PTEN expression blocked proliferation. Next, we combined PTEN deficiency with
      beta-catenin activation and found that this caused papillary UCC. These tumours
      had increased pAKT signalling and were dependent on mammalian target of rapamycin
      (mTOR). Importantly, in human UCC, there was a significant correlation between
      high levels of beta-catenin and pAKT (and low levels of PTEN). Taken together
      these data show that deregulated Wnt signalling has a critical role in promoting
      UCC, and suggests that human UCC that have high levels of Wnt and PI3 kinase
      signalling may be responsive to mTOR inhibition.

PMID- 20818429
TI  - Redox-dependent Brca1 transcriptional regulation by an NADH-sensor CtBP1.
AB  - C-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor and
      metabolic sensory protein, which often represses tumor suppressor genes. Hence,
      we sought to determine if CtBP1 affects expression of the tumor suppressor Brca1
      in head and neck tissue, as downregulation of Brca1 begins at the early stages of
      head and neck squamous cell carcinomas (HNSCCs). We found that CtBP1 represses
      Brca1 transcription by binding to the E2F4 site of the Brca1 promoter.
      Additionally, the recruitment of CtBP1 to the Brca1 promoter is redox-dependent,
      that is, increased at high NADH levels in hypoxic conditions. Further,
      immunostaining using a human HNSCC tissue array revealed that nuclear CtBP1
      staining began to accumulate in hyperplasic lesions and HNSCCs, this staining
      correlated with Brca1 downregulation in these lesions. Pharmacological disruption
      of CtBP1 binding to Brca1 promoter by the antioxidant Tempol, which reduces NADH
      levels, relieved CtBP1-mediated repression of Brca1, leading to increased DNA
      repair in HNSCC cells. As tumor cells are generally hypoxic with increased NADH
      levels, the dynamic control of Brca1 by a 'metabolic switch' found in this study
      not only provides an important link between tumor metabolism and tumor suppressor
      expression but also suggests a potential chemo preventative or therapeutic
      strategy for HNSCC by blocking NADH-dependent CtBP1 activity at early stages of
      HNSCC carcinogenesis.

PMID- 20818430
TI  - AP1 factor inactivation in the suprabasal epidermis causes increased epidermal
      hyperproliferation and hyperkeratosis but reduced carcinogen-dependent tumor
      formation.
AB  - Activator protein one (AP1) (jun/fos) factors comprise a family of
      transcriptional regulators (c-jun, junB, junD, c-fos, FosB, Fra-1 and Fra-2) that
      are key controllers of epidermal keratinocyte survival and differentiation, and
      are important drivers of cancer development. Understanding the role of these
      factors in epidermis is complicated by the fact that each member is expressed in
      defined cell layers during epidermal differentiation, and because AP1 factors
      regulate competing processes (that is, proliferation, apoptosis and
      differentiation). We have proposed that AP1 factors function differently in basal
      versus suprabasal epidermis. To test this, we inactivated suprabasal AP1 factor
      function in mouse epidermis by targeted expression of dominant-negative c-jun
      (TAM67), which inactivates function of all AP1 factors. This produces increased
      basal keratinocyte proliferation, delayed differentiation and extensive
      hyperkeratosis. These findings contrast with previous studies showing that basal
      layer AP1 factor inactivation does not perturb resting epidermis. It is
      interesting that in spite of extensive keratinocyte hyperproliferation,
      susceptibility to carcinogen-dependent tumor induction is markedly attenuated.
      These novel observations strongly suggest that AP1 factors have distinct roles in
      the basal versus suprabasal epidermis, confirm that AP1 factor function is
      required for normal terminal differentiation, and suggest that AP1 factors have a
      different role in normal epidermis versus cancer progression.

PMID- 20818431
TI  - DNA damage stress response in germ cells: role of c-Abl and clinical
      implications.
AB  - Cells experiencing DNA damage undergo a complex response entailing cell-cycle
      arrest, DNA repair and apoptosis, the relative importance of the three being
      modulated by the extent of the lesion. The observation that Abl interacts in the
      nucleus with several proteins involved in different aspects of DNA repair has led
      to the hypothesis that this kinase is part of the damage-sensing mechanism.
      However, the mechanistic details underlying the role of Abl in DNA repair remain
      unclear. Here, I will review the evidence supporting our current understanding of
      Abl activation following DNA insults, while focusing on the relevance of these
      mechanisms in protecting DNA-injured germ cells. Early studies have shown that
      Abl transcripts are highly expressed in the germ line. Abl-deficient mice exhibit
      multiple abnormalities, increased perinatal mortality and reduced fertility.
      Recent findings have implicated Abl in a cisplatin-induced signaling pathway
      eliciting death of immature oocytes. A p53-related protein, TAp63, is an
      important immediate downstream effector of this pathway. Of note, pharmacological
      inhibition of Abl protects the ovarian reserve from the toxic effects of
      cisplatin. This suggests that the extent of Abl catalytic outputs may shift the
      balance between survival (likely through DNA repair) and activation of a death
      response. Taken together, these observations are consistent with the evolutionary
      conserved relationship between DNA damage and activation of the p53 family of
      transcription factors, while shedding light on the key role of Abl in dictating
      the fate of germ cells upon genotoxic insults.

PMID- 20818432
TI  - Transgenic expression of human cathepsin B promotes progression and metastasis of
      polyoma-middle-T-induced breast cancer in mice.
AB  - Elevated expression of the cysteine protease cathepsin B (CTSB) has been
      correlated with a poor prognosis for cancer patients. In order to model high CTSB
      expression in mammary cancer, transgenic mice expressing human CTSB were crossed
      with transgenic polyoma virus middle T oncogene breast cancer mice (mouse mammary
      tumor virus-PymT), resulting in a 20-fold increase in cathepsin B activity in the
      tumors of double-transgenic animals. CTSB expression did not affect tumor onset,
      but CTSB transgenic mice showed accelerated tumor growth with significant
      increase in weight for end-stage tumors, as well as an overall worsening in their
      histopathological grades. Notably, the lung metastases in the CTSB transgenic
      animals were found to be both significantly larger and to occur at a
      significantly higher frequency. Ex vivo analysis of primary PymT tumor cells
      revealed no significant effects from elevated CTSB levels on tumor cell
      characteristics, that is, the formation of tumor cell colonies and the sprouting
      of invasive strands from PymT cell spheroids. However, tumors from CTSB
      overexpressing mice showed increased numbers of tumor-associated B cells and mast
      cells. In addition, more CD31+ endothelial cells were detected in these tumors,
      correlating with higher levels of vascular endothelial growth factor (VEGF) being
      present in the tumor and serum. We conclude that elevated proteolytic CTSB
      activity facilitates progression and metastasis of PymT-induced mammary
      carcinomas, and is associated with increased immune cell infiltration, enhanced
      VEGF levels and the promotion of tumor angiogenesis.

PMID- 20818433
TI  - Hyperactivation of MEK-ERK1/2 signaling and resistance to apoptosis induced by
      the oncogenic B-RAF inhibitor, PLX4720, in mutant N-RAS melanoma cells.
AB  - Activating mutations in B-RAF and N-RAS occur in ~60 and ~15% of melanomas,
      respectively. The most common mutation in B-RAF is V600E, which activates B-RAF
      and the downstream MEK-ERK1/2 pathway. Thus, B-RAF(V600E) is a viable therapeutic
      target. PLX4720 is a selective inhibitor of mutant B-RAF and its analog, PLX4032,
      is currently undergoing clinical trials in melanoma. However, the effects of
      PLX4720 across the genotypic spectrum in melanoma remain unclear. Here, we
      describe that PLX4720 treatment rapidly induces hyperactivation of the MEK-ERK1/2
      pathway in mutant N-RAS melanoma cells. Furthermore, we demonstrate that C-RAF is
      the major RAF isoform involved in this process. Importantly, PLX4720-induced
      hyperactivation of the MEK-ERK1/2 pathway promotes resistance to apoptosis in
      both non-invasive and invasive mutant N-RAS melanoma cells but does not enhance
      cell cycle properties. These findings underscore the need to genotypically
      stratify melanoma patients before enrollment on a mutant B-RAF inhibitor trial.

PMID- 20818434
TI  - Insulin-like growth factor 1 receptor antibody induces rhabdomyosarcoma cell
      death via a process involving AKT and Bcl-x(L).
AB  - Insulin-like growth factors (IGFs) and their receptor, IGF-1 receptor (IGF1R),
      have important roles in growth, development, stress response, aging and cancer.
      There are many agents that inhibit IGF1R in oncology clinical development, and in
      some cases, they have been associated with rapid tumor regression. However, it is
      not clear by which process these targeted agents induce cancer cell death and how
      to predict such tumor responses. Here, we showed that IGF1R antibody led to rapid
      cell death and tumor regression in some rhabdomyosarcoma (RMS) cells. Mechanistic
      analysis revealed a rapid onset of mitochondrial-dependent apoptosis, including
      mitochondrial depolarization, cytochrome C release and the activation of specific
      caspases. The antibody sensitive cells had greater dependence on AKT for
      maintaining downstream signaling and the expression of a constitutively active
      AKT, which restored AKT-signaling in these cells, inhibited anti-IGF1R induced
      cell death. Further analysis showed IGF1R antibody-induced hypophosphorylation of
      BAD and activation of downstream BAX. Interestingly, the examination of RMS cell
      lines and tumors revealed an inverse correlation between elevated IGF1R and Bcl-2
      level (P=0.033), with the sensitive cells lacking Bcl-2 expression. The
      overexpression of BAD specific target, Bcl-x(L), conferred resistance, whereas
      Bcl-x(L) knockdown sensitized cells lacking Bcl-2 to anti-IGF1R-induced cell
      death. We propose that RMS pathogenesis involves increased IGF1R expression that
      enhances AKT and Bcl-x(L)-mediated cell survival, and the blockage of IGF1R
      results in inhibition of survival signal from Bcl-x(L) and cell death in the
      sensitive Bcl-2 negative cells.

PMID- 20818435
TI  - The RET/PTC3 oncogene activates classical NF-kappaB by stabilizing NIK.
AB  - The oncogenic fusion protein RET/PTC3 (RP3) that is expressed in papillary
      thyroid carcinoma (PTC) and thyroid epithelia in Hashimoto's thyroiditis
      activates nuclear factor-kappa B (NF-kappaB) and induces pro-inflammatory gene
      expression; however, the mechanism of this activation is unknown. To address
      this, we expressed RP3 in murine embryonic fibroblasts (MEFs) lacking key
      classical and noncanonical NF-kappaB signaling components. In wild-type MEFs, RP3
      upregulated CCL2, CXCL1, granulocyte-macrophage colony-stimulating factor and
      tumor necrosis factor expression and activated classical but not noncanonical NF
      kappaB. RP3-activated NF-kappaB in IkappaB kinase (IKK)beta(-/-) MEFs but not
      IKKalpha- or NF-kappaB essential modulator (NEMO)-deficient cells and activation
      was inhibited by a peptide that blocks NEMO binding to the IKKs. RP3 increased
      the levels of NF-kappaB-inducing kinase (NIK) and did not activate NF-kappaB in
      NIK-deficient MEFs. Notably, NIK stabilization was not accompanied by TRAF3
      degradation demonstrating that RP3 disrupts normal basal NIK regulation. Dominant
      negative NIK blocked RP3-induced NF-kappaB activation and an RP3 signaling mutant
      (RP3(Y588F)) did not stabilize NIK. Finally, examination of PTC specimens
      revealed strong positive staining for NIK. We therefore conclude that RP3
      activates classical NF-kappaB via NIK, NEMO and IKKalpha. Importantly, our
      findings reveal a novel mechanism for oncogene-induced NF-kappaB activation via
      stabilization of NIK.

PMID- 20818436
TI  - Numb activates the E3 ligase Itch to control Gli1 function through a novel
      degradation signal.
AB  - Hedgehog pathway regulates tissue patterning and cell proliferation. Gli1
      transcription factor is the major effector of Hedgehog signaling and its
      deregulation is often associated to medulloblastoma formation. Proteolytic
      processes represent a critical mechanism by which this pathway is turned off.
      Here, we characterize the regulation of an ubiquitin-mediated mechanism of Gli1
      degradation, promoted by the coordinated action of the E3 ligase Itch and the
      adaptor protein Numb. We show that Numb activates the catalytic activity of Itch,
      releasing it from an inhibitory intramolecular interaction between its homologous
      to E6-AP C-terminus and WW domains. The consequent activation of Itch, together
      with the recruitment of Gli1 through direct binding with Numb, allows Gli1 to
      enter into the complex, resulting in Gli1 ubiquitination and degradation. This
      process is mediated by a novel Itch-dependent degron, composed of a combination
      of two PPXYs and a phospho-serine/proline motifs, localized in Gli1 C-terminal
      region, indicating the role of two different WW docking sites in Gli1
      ubiquitination. Remarkably, Gli1 protein mutated in these modules is no longer
      regulated by Itch and Numb, and determines enhanced Gli1-dependent
      medulloblastoma growth, migration and invasion abilities, as well as in vitro
      transforming activity. Our data reveal a novel mechanism of regulation of Gli1
      stability and function, which influences Hedgehog/Gli1 oncogenic potential.

PMID- 20818437
TI  - MI-219-zinc combination: a new paradigm in MDM2 inhibitor-based therapy.
AB  - Zinc has a crucial role in the biology of p53 in that p53 binds to DNA through a
      structurally complex domain stabilized by zinc atom. The p53 negative regulator
      MDM2 protein also carries a C-terminal RING domain that coordinates two zinc
      atoms, which are responsible for p53 nuclear export and proteasomal degradation.
      In this clinically translatable study, we explored the critical role of zinc on
      p53 reactivation by MDM2 inhibitor, MI-219, in colon and breast cancer cells.
      ZnCl(2) enhanced MI-219 activity (3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT), apoptosis and colony formation), and chelation
      of zinc not only blocked the activity of MI-219, but also suppressed reactivation
      of the p53 and its downstream effector molecules p21(WAF1) and Bax. N,N,N'N'
      tetrakis(-)[2-pyridylmethyl]-ethylenediamine (TPEN), a specific zinc chelator,
      but not 1,2-bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (Bapta-AM), a
      calcium chelator, blocked MI-219-induced apoptosis. Nuclear localization is a
      prerequisite for proper functioning of p53 and our results confirm that TPEN, and
      not Bapta-AM, could abrogate p53 nuclear localization and it interfered with p53
      transcriptional activation. Addition of zinc suppressed the known p53 feedback
      MDM2 activation, which could be restored by TPEN. Co-immunoprecipitation studies
      verified that MI-219-mediated MDM2-p53 disruption could be suppressed by TPEN and
      restored by zinc. As such, single-agent therapies that target MDM2 inhibition,
      without supplemental zinc, may not be optimal in certain patients owing to the
      less recognized mild zinc deficiency among the 'at-risk population' as in the
      elderly who are more prone to cancers. Therefore, use of supplemental zinc with
      MI-219 will benefit the overall efficacy of MIs and this potent combination
      warrants further investigation.

PMID- 20818438
TI  - Remodeling of VE-cadherin junctions by the human herpes virus 8 G-protein coupled
      receptor.
AB  - Kaposi Sarcoma (KS) are opportunistic tumors, associated with human herpes virus
      8 (HHV8) infection. KS development is highly favored by immune-depression and
      remains the second most frequent tumor in acquired immune deficiency syndrome
      patients. Although it has been shown that experimental expression of the HHV8 G
      protein-coupled receptor (vGPCR) in the endothelial compartment is alone
      sufficient to recapitulate the formation and progression of KS-like lesions, its
      functional effects on endothelial homeostasis are not fully understood. Here we
      show that vGPCR expression in endothelial cells induces an increase in
      paracellular permeability both in vivo and in vitro. By using pharmacological
      inhibitors and small interference RNA-based knockdown, we demonstrate an
      essential role for the PI(3)Kinase-gamma/Rac nexus in vGPCR-mediated
      permeability. This was further accompanied by dramatic remodeling of VE-cadherin
      dependent cell-cell junctions. Importantly, this in vitro vGPCR-initiated
      signaling signature was observed in a large panel of human KS. Altogether, our
      results support the hypothesis that endothelial vGPCR signaling is co-opted in
      KS, and unveil new key cellular targets for therapeutic intervention.

PMID- 20818439
TI  - CD133 suppresses neuroblastoma cell differentiation via signal pathway
      modification.
AB  - CD133 (prominin-1) is a transmembrane glycoprotein expressed on the surface of
      normal and cancer stem cells (tumor-initiating cells), progenitor cells, rod
      photoreceptor cells and a variety of epithelial cells. Although CD133 is widely
      used as a marker of various somatic and putative cancer stem cells, its
      contribution to the fundamental properties of cancer cells, such as tumorigenesis
      and differentiation, remains to be elucidated. In the present report, we found
      that CD133 was expressed in several neuroblastoma (NB) cell lines/tumor samples.
      Intriguingly, CD133 repressed NB cell differentiation, for example neurite
      extension and the expression of differentiation marker proteins, and was
      decreased by several differentiation stimuli, but accelerated cell proliferation,
      anchorage-independent colony formation and in vivo tumor formation of NB cells.
      NB cell line and primary tumor-sphere experiments indicated that the molecular
      mechanism of CD133-related differentiation suppression in NB was in part
      dependent on neurotrophic receptor RET tyrosine kinase regulation. RET
      transcription was suppressed by CD133 in NB cells and glial cell line-derived
      neurotrophic factor treatment failed to induce RET in CD133-expressing cells; RET
      overexpression rescued CD133-related inhibition of neurite elongation. Of note,
      CD133-related NB cell differentiation and RET repression were mainly dependent on
      p38MAPK and PI3K/Akt pathways. Furthermore, CD133 has a function in growth and
      RET expression in NB cell line- and primary tumor cell-derived tumor spheres. To
      the best of our knowledge, this is the first report of the function of CD133 in
      cancer cells and our findings may be applied to improve differentiation induction
      therapy for NB patients.

PMID- 20818440
TI  - Activation of the hedgehog pathway confers a poor prognosis in embryonal and
      fusion gene-negative alveolar rhabdomyosarcoma.
AB  - Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and
      comprises two major histological subtypes: alveolar rhabdomyosarcoma (ARMS) and
      embryonal rhabdomyosarcoma (ERMS). Seventy-five percent of ARMS harbor reciprocal
      chromosomal translocations leading to fusion genes of the forkhead transcription
      factor FOXO1 and PAX3 or PAX7. The hedgehog (Hh) pathway has been implied in
      tumor formation and progression of various cancers including RMS. However,
      whether Hh pathway activation presents a general feature of RMS or whether it is
      restricted to specific subgroups has not yet been addressed. Here, we report that
      marker genes of active Hh signaling, that is, Patched1 (Ptch1), Gli1, Gli3 and
      Myf5, are expressed at significantly higher levels in ERMS and fusion gene
      negative ARMS compared with fusion gene-positive ARMS in two distinct cohorts of
      RMS patients. Consistently, Gli1 expression correlates with Ptch1 expression in
      ERMS and fusion gene-negative ARMS, but not in fusion gene-positive ARMS. In
      addition, expression levels of MyoD1 are significantly lower in ERMS and fusion
      gene-negative ARMS, pointing to an inverse association of Hh activation and early
      muscle differentiation. Moreover, Myf5 is identified as a novel excellent class
      predictor for RMS by receiver operating characteristic analysis. Importantly,
      high expression of Ptch1 or low MyoD1 expression significantly correlate with
      reduced cumulative survival in fusion gene-negative RMS underscoring the clinical
      relevance of these findings. By showing that Hh signaling is preferentially
      activated in specific subgroups of RMS, our study has important implications for
      molecular targeted therapies, such as small molecule Hh inhibitors, in RMS.

PMID- 20818441
TI  - A pilot study of reduced toxicity conditioning with BU, fludarabine and
      alemtuzumab before the allogeneic hematopoietic SCT in children and adolescents.
AB  - We report the results of a pilot study of a BU-fludarabine-alemtuzumab (BFA)
      reduced toxicity conditioning (RTC) followed by allogeneic hematopoietic SCT
      (AlloHSCT) in 12 children and adolescents (<21 years) with malignant and non
      malignant diseases. Stem cell sources were: two unrelated cord blood, one
      unrelated BM, two related and seven unrelated PBSC. Positive CD34 selection was
      performed in five unrelated PBSC grafts. RCT was carried out with BFA, and GVHD
      prophylaxis was FK506 and mycophenolate mofetil. The median time for neutrophil
      and platelet engraftment was 16 and 31 days, respectively. The P of developing >=
      grade II, >= grade III aGVHD and cGVHD was 41.6, 25 and 9%, respectively. Only 1
      out of 12 developed >= grade III toxicity. There was one primary and no secondary
      graft failure. Mixed donor chimerism on day 100 and 1 year was median 99 and 96%,
      respectively; >= 90% of recipients achieved >= 80% donor chimerism. The 3-year
      overall survival (OS) in all patients was 91.7 +/- 8% (100% for malignant vs. 80%
      for non-malignant diseases, ns). In all, 11 (91%) patients remain alive at median
      2.8 (0.3-6.8) years. RTC followed by AlloHSCT, based on BFA conditioning, is
      feasible and tolerable in children and adolescents, and results in prompt
      achievement of durable mixed donor chimerism and excellent OS.

PMID- 20818442
TI  - Auto-SCT in refractory celiac disease type II patients unresponsive to cladribine
      therapy.
AB  - Autologous hematopoietic SCT (auto-SCT) has been effective therapy for refractory
      disease, in both malignancies and severe autoimmune diseases. It seems feasible
      and safe for refractory celiac disease (RCD) type II, although long-term results
      have not been evaluated yet. With current therapies, progression into enteropathy
      associated T-cell lymphoma (EATL) occurs in 60-80% patients, with a high
      mortality rate. Therefore, it is important to evaluate new treatment strategies.
      Between March 2004 and February 2010, 18 RCD II patients were evaluated for auto
      SCT preceded by conditioning with fludarabine and melphalan, as a consequence of
      unresponsiveness to cladribine therapy. Adverse events, survival rate, EATL
      development and change in clinical, histological and immunological course were
      monitored. Thirteen patients were transplanted successfully and followed up for
      >2 years, 4-year survival rate was 66%. Only one patient died because of
      transplant-related complications. The majority of patients showed an impressive
      clinical improvement and five a complete histological remission. In five
      patients, auto-SCT could not be performed; they all died with a median survival
      of 5.5 months. EATL was observed in one transplanted patient, only after 4 years
      of follow-up. Auto-SCT after conditioning with high-dose chemotherapy in RCD II
      patients unresponsive to cladribine therapy is feasible and seems promising.

PMID- 20818443
TI  - Role of autotransplantation in the treatment of acute promyelocytic leukemia
      patients in remission: Fukuoka BMT Group observations and a literature review.
AB  - We retrospectively analyzed the outcomes of 26 patients with acute promyelocytic
      leukemia (APL) in the first CR (CR1) or second CR (CR2), who underwent autologous
      PBSCT (auto-PBSCT) between 1992 and 2008. All patients received all-trans
      retinoic acid-based induction therapy. After two courses of consolidation
      chemotherapy, upfront auto-PBSCT was performed in 20 patients in the CR1. Five
      patients had a high WBC count of more than 10 * 10(9)/L (high risk), while 15
      patients had a count of less than 10 * 10(9)/L (low risk) at initial
      presentation. In addition, six patients, who were considered as low-risk patients
      at presentation, had a relapse after three cycles of consolidation and 2 years of
      maintenance therapy, but gained the molecular remission after re-induction and
      consolidation, and underwent auto-PBSCT in the CR2. In 26 recipients, engraftment
      was rapid and no TRM was documented. All 20 patients autotransplanted in CR1 were
      still in CR at a median of 133 months (73-193 months), and six patients who
      underwent auto-PBSCT in CR2 were also still in CR at a median of 41 months (2-187
      months) without maintenance therapy. PML/RARalpha chimeric mRNA was undetectable
      in PBSC or BM samples examined before auto-PBSCT. Despite a small number of cases
      studied, our retrospective observations suggest that auto-PBSCT may be an
      effective treatment option to continue durable CR in the treatment of high-risk
      APL. We review previous reports and discuss the role of autotransplantation in
      the treatment of APL patients in CR.

PMID- 20818444
TI  - Effectiveness of a single 3-mg rasburicase dose for the management of
      hyperuricemia in patients with hematological malignancies.
AB  - Rasburicase was administered at a fixed dose of 3 mg to treat 287 episodes of
      elevated serum uric acid levels (>7 mg/dL) in 247 adult patients with
      hematological malignancies. The median total dose of 36 MUg/kg (range: 18-65) was
      a fraction of the recommended total pediatric dose of 0.75-1.0 mg/kg. The median
      change in uric acid levels at 24 h was -4.1 mg/dL (range: -12 to +1) and -45%
      (range: -95 to +9). Uric acid levels normalized at 24 h in 72% of patients. There
      was no relationship between the weight-based dose and uric acid decline. The only
      predictor of success was the baseline uric acid; the failure rate was 84% with
      baseline level >12 mg/dL and 18% if it was <= 12. Uric acid levels continued to
      decline beyond 24 h in most patients without additional treatment. Serum
      creatinine remained stable over 24 h, and declined over 48 h and 7 days. There
      was no relationship between the extent of reduction in uric acid levels and serum
      creatinine. We conclude that a single 3-mg dose of rasburicase, used with close
      monitoring, is sufficient to treat most adults with uric acid levels up to 12
      mg/dL.

PMID- 20818445
TI  - Mesenchymal stem cell as salvage treatment for refractory chronic GVHD.
AB  - Refractory chronic GVHD (cGVHD) is an important complication after allogeneic
      hematopoietic SCT and is prognostic of poor outcome. MSCs are involved in tissue
      repair and modulating immune responses in vitro and in vivo. From April 2005 to
      October 2008, 19 patients with refractory cGVHD were treated with MSCs derived
      from the BM of volunteers. The median dose of MSCs was 0.6 * 10(6) cells per kg
      body weight. Fourteen of 19 patients (73.7%) responded well to MSCs, achieving a
      CR (n=4) or a PR (n=10). The immunosuppressive agent could be tapered to less
      than 50% of the starting dose in 5 of 14 surviving patients, and five patients
      could discontinue immunosuppressive agents. The median duration between MSC
      administration and immunosuppressive therapy discontinuation was 324 days (range,
      200-550 days). No patients experienced adverse events during or immediately after
      MSC infusion. The 2-year survival rate was 77.7% in this study. Clinical
      improvement was accompanied by the increasing ratio of CD5+CD19+/CD5-CD19+ B
      cells and CD8+CD28-/CD8+CD28+ T cells. In conclusion, transfusion of MSCs
      expanded in vitro, irrespective of the donor, might be a safe and effective
      salvage therapy for patients with steroid-resistant, cGVHD.

PMID- 20818447
TI  - Issues in genetic association studies: limitations of statistical analysis and
      biological plausibility.

PMID- 20818446
TI  - Prevalence of osteonecrosis and associated risk factors in children before
      allogeneic BMT.
AB  - Osteonecrosis (ON) is a debilitating long-term complication of allogeneic BMT
      (allo-BMT), but may begin before allo-BMT in some children because of their
      primary disease treatment. Therefore, to estimate the prevalence and associated
      risk factors for ON before allo-BMT, we conducted a retrospective analysis of
      magnetic resonance (MR) studies of 118 children who underwent first allo-BMT at
      our institution between December 2000 and September 2007. Of the 118 consecutive
      patients, 107 (90.7%) underwent prospective MR studies irrespective of symptoms
      (69 males; median age at allo-BMT 12.9 years), and 11 underwent MR studies for
      symptoms. Among the 107 who had prospective imaging, 23 (21.5%) had ON; nearly
      50% had at least 30% epiphyseal involvement. Knees were more frequently involved
      than were hips; severity of ON was greater in hips. ON prevalence before allo-BMT
      was 23.72% when all 118 patients were included in the denominator. Risk factor
      analysis, limited to MR studies performed irrespective of symptoms, revealed
      female gender (P=0.049) and age ?10 years at the time of MR study (P=0.03) as
      significant risk factors, and primary diagnosis of lymphoid malignancies and
      aplastic anemia trended toward significance. ON before allo-BMT is a common
      occurrence in children.

PMID- 20818448
TI  - Reduction of infection-related mortality after allogeneic PBSCT from HLA
      identical siblings: longitudinal analysis from 1994 to 2008 at a single
      institution.
AB  - Infection-related mortality (IRM) is responsible for a major proportion of all
      cases of non-relapse mortality (NRM) after allogeneic PBSCT (alloPBSCT). We
      analyzed 580 consecutive adults who received a first alloPBSCT from an HLA
      identical sibling from 1994 to 2008 at a single institution to describe the
      severe infections and report the incidence, causes and risk factors for IRM and
      NRM. Both IRM and NRM decreased with time; within the period of 1994-2000, the 2
      year incidence of IRM and NRM was 22 and 31%, respectively, vs 11 and 16% within
      the period of 2001-2008 (P<0.05 for both comparisons). In multivariate analysis,
      the variables that increased IRM were within the earlier period of 1994-2000
      (P<0.01), poor performance status (P<0.01), grade II-IV acute GVHD (P<0.001) and
      invasive fungal infection (IFI) (P<0.001) or CMV disease (P<0.001) after
      transplant. With respect to NRM, earlier time period was also identified as a
      risk factor (P<0.001), as well as IFIs (P<0.001) and CMV disease (P<0.001). The
      intensity of the conditioning regimen had no effect on IRM and NRM. These results
      showed a significant reduction in IRM and NRM over a period of 15 years. The
      development of IFIs and CMV disease continue to have an impact on NRM.

PMID- 20818449
TI  - Incidence and severity of oral mucositis in patients undergoing haematopoietic
      SCT--results of a multicentre study.
AB  - Oral mucositis (OM) is a common side effect experienced during haematopoietic SCT
      (HSCT), and it can have a significant impact on the quality of life of patients.
      A descriptive nurse-led study was undertaken in 19-member centres of the Italian
      national transplant group (GITMO) evaluating incidence, severity and duration of
      OM in patients undergoing HSCT. Data from 1841 patients between 2002 and 2006 was
      analyzed. Initial medical history and oral cavity assessment was performed.
      Assessment was repeated on the day of transplant, then daily, using the WHO
      (World Health Organisation) oral toxicity scale. A total of 71% of the patients
      evaluated developed mucositis and 21.6% developed severe mucositis. Duration of
      OM in most cases lasted for 10-14 days and resolved along with marrow
      reconstitution. Oral mucostitis is a frequent side effect in patients undergoing
      HSCT. The onset of severe mucositis seems to be related to the conditioning
      regimen used. This database provides a descriptive overview of the incidence and
      severity of mucositis and has encouraged participating centres to adopt routine
      evaluation and measurement of the oral cavity. The assessment tools are still
      used in some centres, providing a basis for further collaborative research
      projects.

PMID- 20818450
TI  - Failure of front-line autologous transplant in anaplastic lymphoma kinase
      positive diffuse large B-cell lymphoma.

PMID- 20818452
TI  - Anion recognition by hydrogen bonding: urea-based receptors.
AB  - Since 1992 a variety of urea-based anion receptors have been synthesised, of
      varying complexity and sophistication. This critical review will focus on some
      distinctive aspects of anion recognition by urea derivatives, with a special
      reference to: (i) design and synthesis, (ii) methodologies for the investigation
      of the receptor-anion interaction in solution, (iii) the interpretation of the
      solution behaviour on the basis of the structural interplay between the receptor
      and the anion. It will be shown that the efficiency of urea as a receptor subunit
      depends on the presence of two proximate polarised N-H fragments, capable (i) of
      chelating a spherical anion or (ii) of donating two parallel H-bonds to the
      oxygen atoms of a carboxylate or of an inorganic oxoanion, a property which is
      shared with other diamides, e.g. squaramide. The wide use of urea in the design
      of neutral anion receptors seems to depends on the ease of its synthesis, in
      particular through the reaction of a primary amine group with an isocyanate,
      which allows the high-yield preparation of symmetrically and unsymmetrically
      substituted derivatives (83 references).

PMID- 20818451
TI  - Gold nanostructures: a class of multifunctional materials for biomedical
      applications.
AB  - Gold nanostructures have proven to be a versatile platform for a broad range of
      biomedical applications, with potential use in numerous areas including:
      diagnostics and sensing, in vitro and in vivo imaging, and therapeutic
      techniques. These applications are possible because of the highly favorable
      properties of gold nanostructures, many of which can be tailored for specific
      applications. In the first part of this tutorial review, we will discuss the most
      critical properties of gold nanostructures for biomedical applications: surface
      chemistry, localized surface plasmon resonance (LSPR), and morphology. In the
      second part of the review, we will discuss how these properties can be harnessed
      for a selection of biomedical applications, aiming to give the reader an overview
      of general strategies as well as highlight some recent advances in this field.

PMID- 20818453
TI  - Materials challenges toward proton-conducting oxide fuel cells: a critical
      review.
AB  - The increasing world population and the need to improve quality of life for a
      large percentage of human beings are the driving forces for the search for
      sustainable energy production systems, alternative to fossil fuel combustion.
      Among the various types of alternative energy production technologies, solid
      oxide fuel cells (SOFCs) operating at intermediate temperatures (400-700  degrees
      C) show the advantage of possible use both for stationary and mobile energy
      production. To reach the goal of reducing the SOFC operating temperature, proton
      conducting oxides are gaining wide interest as electrolyte materials. This
      critical review provides a broad overview of the most recent progresses obtained
      tailoring the properties of proton-conducting oxides for fuel cell applications,
      analyzing and comparing the different strategies proposed to match high-proton
      conductivity with good chemical stability (170 references).

PMID- 20818454
TI  - Colorimetric and fluorescent anion sensors: an overview of recent developments in
      the use of 1,8-naphthalimide-based chemosensors.
AB  - This critical review focuses on the development of anion sensors, being either
      fluorescent and/or colorimetric, based on the use of the 1,8-naphthalimide
      structure; a highly versatile building unit that absorbs and emits at long
      wavelengths. The review commences with a short description of the most commonly
      used design principles employed in chemosensors, followed by a discussion on the
      photophysical properties of the 4-amino-1,8-naphthalimide structure which has
      been most commonly employed in both cation and anion sensing to date. This is
      followed by a review of the current state of the art in naphthalimide-based anion
      sensing, where systems using ureas, thioureas and amides as hydrogen-bonding
      receptors, as well as charged receptors have been used for anion sensing in both
      organic and aqueous solutions, or within various polymeric networks, such as
      hydrogels. The review concludes with some current and future perspectives
      including the use of the naphthalimides for sensing small biomolecules, such as
      amino acids, as well as probes for incorporation and binding to proteins; and for
      the recognition/sensing of polyanions such as DNA, and their potential use as
      novel therapeutic and diagnostic agents (95 references).

PMID- 20818455
TI  - Molecular tracers for the PET and SPECT imaging of disease.
AB  - The development of positron emission tomography (PET) and single photon emission
      computed tomography (SPECT) imaging continues to grow due to the ability of these
      techniques to allow the non-invasive in vivo visualisation of biological
      processes at the molecular and cellular levels. As well as finding application
      for the diagnosis of disease, these techniques have also been used in the drug
      discovery process. Crucial to the growth of these techniques is the continued
      development of molecular probes that can bind to the target biological receptor
      with high selectivity. This tutorial review describes the use of PET and SPECT
      for molecular imaging and highlights key strategies for the development of
      molecular probes for the imaging of both cancer and neurological diseases.

PMID- 20818456
TI  - Monitoring and managing responses to climate change at the retreating range edge
      of forest trees.
AB  - Rising temperatures and increasing drought severity linked to global climate
      change are negatively impacting forest growth and function at the equatorial
      range edge of species distributions. Rapid dieback and range retractions are
      predicted to occur in many areas as temperatures continue to rise. Despite
      widespread negative impacts at the ecosystem level, equatorial range edges are
      not well studied, and their responses to climate change are poorly understood.
      Effective monitoring of tree responses to climate in these regions is of critical
      importance in order to predict and manage threats to populations. Remote sensing
      of impacts on forests can be combined with ground-based assessment of
      environmental and ecological changes to identify populations most at risk.
      Modelling may be useful as a 'first-filter' to identify populations of concern
      but, together with many remote sensing methods, often lacks adequate resolution
      for application at the range edge. A multidisciplinary approach, combining remote
      observation with targeted ground-based monitoring of local susceptible and
      resistant populations, is therefore required. Once at-risk regions have been
      identified, management can be adapted to reduce immediate risks in priority
      populations, and promote long-term adaptation to change. However, management to
      protect forest ecosystem function may be preferable where the maintenance of
      historical species assemblages is no longer viable.

PMID- 20818457
TI  - The effect of Tween 80 on eggshell permeabilization in Galleria mellonella (L.)
      (Lepidoptera, Pyralidae).
AB  - The development of a species-specific protocol for dechorionation and
      permeabilization of insect eggs is a necessary prerequisite to cryopreserve the
      embryos. Here we tested different procedures based on heptane or the surfactant
      Tween 80 as an alternative to alkane, evaluating their efficacy and toxicity on
      the early (24 h post-oviposition) and late (75 h post-oviposition) stage embryos.
      Heptane efficiently permeabilized the eggs of G. mellonella but the hatching rate
      ranged from 0.1 to 4.2 percent in the early stage and from 4.3 to 11.2 percent in
      the late stage. The embryos treated with 1.25 percent NaOCl + 0.08 percent Tween
      80 for 2 min showed the same shrinkage and reswelling percentages as eggs exposed
      to heptane for 10 sec, with a significantly higher hatching percentage in the
      early (68.2 +/- 1.5 percent) and late stages (22.4 +/- 3.7 percent). Thus, 0.08
      percent Tween 80 allows sufficient permeabilization of G. mellonella embryos
      without the high toxicity of alkane.

PMID- 20818458
TI  - Comparison of vitrification and encapsulation-dehydration for cryopreservation of
      Thymus moroderi shoot tips.
AB  - Vitrification and encapsulation-dehydration were tested for cryopreservation of
      Thymus moroderi Pau ex Martinez (Labiatae), an endemic plant from south-eastern
      Spain. For vitrification, shoot tips were loaded in a solution containing 0.4 M
      sucrose + 2 M glycerol for 20 min at room temperature, dehydrated in PVS2
      solution for 0-105 min at 0 degree C, then immersed in liquid nitrogen (LN) for
      at least 1 day and rapidly rewarmed. The highest survival (71.4 percent) was
      obtained after 60 min PVS2 dehydration. Encapsulation-dehydration gave slightly
      lower results, with up to 50 percent explants survival. In the optimal protocol,
      donor plants were cold-hardened at 10 degree C for 5 weeks, excised shoot tips
      precultured for 48 h on MS medium with 0.08 M sucrose, encapsulated, pretreated
      in medium with 0.75 M sucrose for 19 h, desiccated to 22 percent moisture content
      (fresh weight basis), and immersed in LN. Vitrification thus appears more
      suitable than encapsulation-dehydration for cryopreservation of T. moroderi shoot
      tips.

PMID- 20818459
TI  - Comparing cooling systems for the COBE 2991 cell separator used in the
      purification of human pancreatic islets of Langerhans.
AB  - Two different approaches of controlled cooling of the COBE 2991 cell-separator
      for islet purification were evaluated. The first method is the new Geneva COBE
      cooling system (GCCS), which consists of an electronically controlled liquid
      nitrogen injection system. The second is the University of Illinois at Chicago
      cooling system (UICCS), which consists of a specially designed "Cold Room"
      maintained at 1-8 C. For the GCCS, the mean temperatures of the gradient
      solutions were measured at the beginning and end of centrifugation were found to
      be 7 +/-0.7 C and 6.8 +/-0.6 C respectively. For the UICCS, the mean temperature
      of the gradients at the beginning and end of centrifugation were 4.7 +/-0.53 C
      and 7.03 C+/-0.91 C respectively. The presented COBE cooling systems can easily
      be adapted to a COBE 2991 cell-separator and are efficient in maintaining
      gradient solutions at a defined low temperature during centrifugation.

PMID- 20818460
TI  - In vitro 17beta-oestradiol release as a marker for follicular survival in
      cryopreserved intact bovine ovaries.
AB  - Transplantation of cryopreserved intact ovaries from cancer patients is a
      technically challenging option for restoring fertility after sterilizing cancer
      therapy. In this paper we describe an assay based on 17beta-oestradiol
      (oestradiol) production, to monitor the functional damage sustained by the
      ovarian tissue during the freeze/thawing procedure. To this end, fresh bovine
      ovarian cortical biopsies were cultured in vitro for 7 days. As a control, the
      oestradiol release of biopsies that had sustained maximal cryodamage was
      analyzed. In addition the oestradiol release by cortical biopsies from two ME2SO
      perfused and cryopreserved intact ovaries was analyzed. Oestradiol production
      could be measured in culture supernatants, while oestradiol release of maximal
      cryo-damaged biopsies was at background levels. In vitro oestradiol release by
      cortical biopsies can be used as a functional marker for cryo-damage and
      indicates that our assay is suitable to optimize the cryopreservation procedure
      of intact ovaries.

PMID- 20818461
TI  - Do ice nucleating agents limit the supercooling ability of the land snail Cornu
      aspersum?
AB  - The supercooling ability of adults and eggs of the partially freezing tolerant
      land snail Cornu aspersum remains limited to high subzero temperatures (ca. -5
      degree C) whatever the conditions, suggesting the presence of ice nucleating
      agents (INAs). In this study, we investigated the nucleation activity of the
      digestive tract of adult snails, eggs and their direct environment: food, faeces
      and soil. The mucous ribbon always present in the distal intestine of adults
      exhibited a heat-sensitive (i.e. organic) nucleation activity, close to that of
      the entire snails during dormant states (aestivation and hibernation). However, a
      microbial nature of these INAs could not be established in inactive snails. The
      food provided to active snails contained ice nucleating bacteria, which followed
      the digestive tract to be found in the intestine and in the faeces, but with a
      decreasing concentration along the transit. Eggshells also presented a heat
      sensitive nucleation activity, which could be related to its structure. Moreover,
      eggs are laid directly in the soil which contained both organic and mineral INAs.
      This study is the first to demonstrate the implication of organic INAs in the
      cold hardiness of a terrestrial gastropod.

PMID- 20818462
TI  - Vitrification-based cryopreservation of Grammatophyllum speciosum protocorm.
AB  - Three vitrification-based methods for the cryopreservation of Grammatophyllum
      speciosum protocorms were invesigated: droplet-vitrification, encapsulation
      dehydration and encapsulation-vitrification. Protocorms, 0.1 cm in diameter,
      developed from 2-month-old germinating seeds were used. For droplet
      vitrification, protocorms were precultured on filter paper soaked in half
      strength Murashige and Skoog medium (half strength MS) containing 0.4 M sucrose
      at 25 2 degree C for 2 d, followed by soaking in loading solution (2 M glycerol
      and 0.4 M sucrose in half strength MS liquid medium) for 20 min and then
      dehydrated with PVS2 solution [30 percent (w/v) glycerol, 15 percent (w/v)
      ethylene glycol and 15 percent (w/v) dimethyl sulfoxide in half strength MS
      liquid medium containing 0.4 M sucrose at pH 5.7] for 30 min. For encapsulation
      dehydration, encapsulated protocorms were precultured in half strength MS liquid
      medium containing 0.4 M sucrose on a shaker (110 rpm) at 25 f 2 degree C for 2 d,
      followed by soaking in the same loading solution for 20 min and then exposed to a
      sterile air-flow at 2.5 inches/water column from the laminar air-flow cabinet for
      8 h. For encapsulation-vitrification, encapsulated protocorms were precultured in
      half strength MS liquid medium containing 0.4 M sucrose for 1 or 2 d, followed by
      soaking in the same loading solution for 20 min and then dehydrated with PVS2
      solution for 60 min. For all three methods, preculturing with 0.4 M sucrose for 2
      d resulted in a significant induction of dehydration and freezing tolerance. The
      cryopreservation results showed highest protocorm regrowth after droplet
      vitrification (38 percent), followed by encapsulation-dehydration (24 percent)
      and encapsulation-vitrification (14 percent). Plantlets developed from these
      three methods did not show any abnormal characteristics or ploidy level change
      when investigated by flow cytometry.

PMID- 20818463
TI  - Relationship of a dominant advanced glycation end product, serum carboxymethyl
      lysine, and abnormal glucose metabolism in adults: the Baltimore Longitudinal
      Study of Aging.
AB  - BACKGROUND AND OBJECTIVES: Although hyperglycemia is thought to increase the
      generation of advanced glycation end products (AGEs), studies have not shown a
      consistent relationship between abnormal glucose metabolism and serum AGEs. We
      investigated the relationship between a dominant serum AGE, N-carboxymethyl
      lysine (CML), and glucose metabolism. SUBJECTS AND METHODS: Serum CML, fasting
      plasma glucose, and glucose tolerance were measured in 755 adults in the
      Baltimore Longitudinal Study of Aging. Fasting plasma glucose was categorized as
      normal (< or = 99 mg/dL), impaired (100-125 mg/dL), and diabetic (> 125 mg/dL).
      Two-hour plasma glucose on oral glucose tolerance testing was categorized as
      normal (< or = 139 mg/dL), impaired (140-199 mg/dL), and diabetic (> or = 200
      mg/dL). RESULTS: The proportion of adults with normal, impaired, and diabetic
      fasting plasma glucose was 73.8%, 22.9%, and 2.9%, respectively, and the
      proportion with normal, impaired, and diabetic 2-hour plasma glucose was 73.1%,
      19.2%, and 7.7%, respectively. Serum CML (microg/mL) was not associated with
      abnormal fasting plasma glucose (Odds Ratio [O.R.] 0.60, 95% Confidence Interval
      [C.I.] 0.15-2.36, P = 0.47) in a multivariate, ordered logistic regression model,
      adjusting for age, race, gender, body mass index, and chronic diseases. Serum CML
      (microg/mL) was associated with abnormal 2-hour plasma glucose on glucose
      tolerance testing (O.R. 0.15, 95% C.I. 0.04-0.63, P = 0.009) in a multivariate,
      ordered logistic regression model, adjusting for the same covariates.
      CONCLUSIONS: Elevated CML, a dominant AGE, was not associated with elevated
      fasting plasma glucose and was associated with a reduced odds of abnormal glucose
      tolerance in older community-dwelling adults.

PMID- 20818465
TI  - The time has arrived to meet the challenge of Alzheimer's disease in Europe.

PMID- 20818464
TI  - BMI, life-style and psychological conditions in a sample of elderly Italian men
      and women.
AB  - OBJECTIVES: To identify the relationship among cognitive status, psychological
      conditions, anthropometric measurements and life-style in a sample of elderly
      Italian men and women. METHODS: Three hundred and six volunteers for ZINCAGE
      Project recruited. The sample was made up of healthy older adults living in the
      Marche Region aged 65 and over. All elderly were given a complete medical,
      anthropometric assessment, and psycho-social evaluation. RESULTS: Overall, the
      participants perceived themselves to be in very good or good (22%) or fair (69%)
      health; only 9% reported a poor health status. The 46% of the sample fell within
      the normal body mass index (BMI) range, though 38% were overweight, 12% were
      obese, and only 4% were underweight. In both sexes, BMI significantly decreased
      with age (p<0.001). BMI was positively associated with performing sedentary
      activities (r=0.188; p<0.001). Levels of both sedentary (r=0.221; p<0.001) and
      non-sedentary (r=0.258; p<0.001) leisure activities were positively associated
      with education level (p<0.05). It was found that lower scores of physical
      activity were associated to higher scores of Geriatric Depression Scale (r=
      0.425; p<0.01), lower scores of Mini Mental State Examination (r=0.266; p<0.001)
      and higher score of Perceived Stress Scale (r=-0.131; p<0.05). CONCLUSION: Men
      and women lead different lifestyles and have a different psychological status,
      with advancing age consequently stressing the need for healthy lifestyle
      programmes particularly in the case of overweight and obese elderly people.

PMID- 20818466
TI  - Assessing attitudes and behaviours surrounding Alzheimer's disease in Europe: key
      findings of the Important Perspectives on Alzheimer's Care and Treatment (IMPACT)
      survey.
AB  - The Important Perspectives on Alzheimer's Care and Treatment (IMPACT) survey is
      an assessment in Europe of the attitudes of caregivers, physicians, the general
      public and payors towards Alzheimer's disease and dementia. This was an Internet
      based questionnaire study, which sought to determine the opinion and perception
      of responders on issues relating to ageing and dementia. There were additional
      questions for caregivers on the impact of caregiving on their life. Responses
      were analysed from 949 members of the general public, 500 physicians (generalists
      and specialists), 250 caregivers and 50 payors from 5 countries--France, Germany,
      Italy, Spain and the United Kingdom. The survey highlighted the difficulty of
      diagnosing dementia, especially in the initial stages of the disease. The average
      time from first noticing symptoms to diagnosis varied from 36 to 63 weeks.
      Caregivers and the general public felt they had insufficient information about
      the benefits of treatment and care, although more than half the general public,
      caregiver and physician responders agreed that early treatment could delay the
      progression of the disease. The majority of respondents recognised the
      devastating effects of AD on caregivers and families, and a majority of
      caregivers, the general public and physicians agreed that their governments fail
      to view AD as a health care priority. This study occurs roughly 5 years after a
      similar survey, and provides a timely update. Despite some important differences
      between the methodologies used in these surveys, diagnosis of dementia is still a
      key issue, especially amongst generalists, as is the provision of information and
      support to caregivers. Despite the prevalence of AD in the ageing population of
      Europe, the perception within each of the 5 countries surveyed is that AD is not
      viewed as a health care priority.

PMID- 20818467
TI  - Evolving attitudes to Alzheimer's disease among the general public and caregivers
      in Europe: findings from the IMPACT survey.
AB  - Understanding and appreciating the awareness of, and attitudes towards,
      Alzheimer's disease (AD) in the general public is of paramount importance to
      those charged with the development of health care policy. Furthermore, it is
      essential that this policy be formulated with consideration given to both the
      attitudes of the general population and to those within society more directly
      affected by AD; namely, the caregivers of patients with the disease. In the
      IMPACT survey, approximately 1000 members of the general public and 250
      caregivers in 5 European countries (France, Germany, Italy, Spain, and the United
      Kingdom) completed a 30-minute, Web-based questionnaire. In this article, we
      compare and contrast the attitudes and opinions of these populations in an
      attempt to define specific themes. Indeed, caregivers were more concerned about
      consequences of growing old and were more fearful of AD than general public
      respondents, although a high proportion in both groups acknowledged the
      significant impact of the disease. Similarly, although most respondents in the 2
      groups recognised that early signs and symptoms of AD are difficult to detect,
      caregivers were more skeptical of the abilities of both primary physicians and
      specialists to detect these early signs and symptoms. In terms of treatment,
      caregivers were less convinced of the effectiveness of treatment beyond the early
      stages of AD and more likely to agree that current treatments are associated with
      side effects. Respondents in both groups had a negative view of their
      government's investment in AD, but caregivers, particularly those in France,
      Spain and the United Kingdom, were more likely to feel that their government acts
      as a barrier to treatment. Some survey respondents from the 2 groups also had a
      negative view of their governments' attempts to raise awareness of AD and make
      its treatment a high priority. Overall, comparison of responses from these 2
      groups suggests that caregivers' personal experiences of AD profoundly affect
      their attitudes and perceptions surrounding the disease.

PMID- 20818468
TI  - Assessing physician attitudes and perceptions of Alzheimer's disease across
      Europe.
AB  - Given the important role that physicians play in clinical care, disease advocacy,
      national health policy making and clinical research, the IMPACT survey sought to
      assess the attitudes and perceptions of physicians in 3 general categories:
      diagnosis and treatment of Alzheimer's disease (AD); caregivers and families of
      patients with AD; and the role of government in dealing with this disease and its
      consequences. Survey respondents comprised a total of 250 generalists and 250
      specialists (neurologists, geriatricians, neuro-psychiatrists, psychiatrists and
      psychogeriatricians) from France, Germany, Italy, Spain and the United Kingdom.
      Physicians were aged 25 to 69 years, in practice for between 5 and 30 years and
      currently spending more than 50% of their time in direct patient care. Results
      showed that a sizable majority of physicians throughout Europe, specialists and
      generalists alike, agree that: 1) AD is underdiagnosed and undertreated; 2)
      patients and families are not prepared to recognise the early symptoms of the
      disease; 3) early treatment can help to slow the progression of the disease; and
      4) more effective treatments are needed. Attitudes were statistically
      significantly different between some groups of physicians regarding disclosure of
      the diagnosis of AD, the benefits of lifestyle modification, and the value of AD
      specific medication in patients whose symptoms are worsening. Differences in
      attitudes and perceptions of AD between specialists and generalists were limited;
      differences between countries were more common and of greater magnitude,
      particularly with respect to barriers to the use of prescription medications.

PMID- 20818469
TI  - Clinical practice patterns of generalists and specialists in Alzheimer's disease:
      what are the differences, and what difference do they make?
AB  - Optimising the roles played by both generalists and specialists in the diagnosis
      and treatment of Alzheimer's disease (AD) could have a major impact on the
      quality and cost of patient care. Therefore, one aim of the IMPACT survey was to
      characterise the similarities and differences between these 2 categories of
      physicians, in 5 different European countries, across a number of domains
      relevant to the medical care of people at risk for AD and those with the disease.
      Physician respondents comprised 250 generalists and 250 specialists from 5
      European countries--France, Germany, Italy, Spain, and the United Kingdom. A
      substantial majority of generalists were either general practitioners or family
      physicians; the majority of specialists were neurologists. In April and May 2009,
      physician respondents completed a 30-minute, Web-based questionnaire during which
      they were presented with a number of multiple-choice-type questions concerning
      their knowledge of AD, approach to diagnosis and treatment of AD and experience
      of providing care for people with dementia. Generalists reported that 45% of
      their AD patients had mild symptoms at the initial visit compared with 60% for
      specialists (P < 0.001). Specialists claimed that they diagnose patients with AD
      themselves in 65% of cases versus 33% for generalists (P < 0.001). The main
      prescription treatment options employed were AD-specific medication (90%) and
      medication for mood or behaviour (78%). A similar percentage of generalists and
      specialists (77% and 75%) initiate drug treatment within 1 month of diagnosis.
      Overall, there were more similarities than differences between specialists and
      generalists regarding a broad spectrum of issues relating to AD; differences
      between countries appear to be greater than differences between physician groups.

PMID- 20818470
TI  - Implications of the Impact Survey for payors across Europe.
AB  - People involved with development of health care policy must be appreciative of
      the social and economic challenges that will likely develop as a result of the
      rise in Alzheimer's disease (AD) as the 21st century progresses. Their attitudes,
      perceptions and understanding regarding AD were captured in the IMPACT survey, a
      30-minute Web-based questionnaire. Fifty health policy managers and decision
      makers (payors) were recruited, 10 each from 5 European countries--France,
      Germany, Italy, Spain and the United Kingdom. Most payors felt that AD was
      underdiagnosed and undertreated in their country (80% and 68%, respectively).
      Half of all payors felt that their government did not invest enough in treating
      AD, and 30% felt their government hindered access to drug therapy. Payors
      believed that treatment should be initiated as early as possible after a
      diagnosis of AD (82%), and that early treatment can delay progression of the
      disease (82%). Even more than caregivers, payors agreed that AD can have
      devastating effects on the family of the sufferer (90% vs 75%; P<0.05). Payors
      more often cited cancer, stroke and heart disease than AD as affecting their
      budgets, but cited AD more often than depression, diabetes, HIV/AIDs and
      arthritis. Cost savings were seen as the most important factor regarding policy
      decisions. These attitudes of the surveyed payors towards AD and the patients and
      caregivers affected by it suggest that they may advocate for national and
      international policies that will facilitate earlier diagnosis and improved access
      to treatment.

PMID- 20818471
TI  - Screening for cognitive impairment, Alzheimer's disease and other dementias:
      opinions of European caregivers, payors, physicians and the general public.
AB  - The IMPACT survey queried physicians, caregivers, payors and members of the
      general public from 5 European countries (France, Germany, Italy, Spain and the
      United Kingdom) regarding their opinions towards screening for Alzheimer's
      disease (AD) as part of a 30-minute Web-based questionnaire conducted between
      April and May 2009. A larger proportion of caregivers (84%) and members of the
      general public (80%) than of physicians (56%) or payors (40%) viewed routine
      screening for AD as extremely or very important (P < 0.001 for caregivers or
      general public vs physicians or payors). When asked if everyone should be
      routinely screened for AD at age 65, a smaller proportion of physicians (42%) and
      payors (44%) than members of the general public (81%) or caregivers (80%) agreed
      (P < 0.001 for caregivers or general public vs physicians or payors). These
      opinions were generally consistent across the 5 countries for each respondent
      group. A notable exception was physician respondents from Italy, where most
      generalists and specialists actually favoured screening. Overall, generalists had
      a more positive attitude towards screening than specialists. The most frequently
      cited reason given by those who did not favour routine screening at age 65 was
      screening inaccuracy. This article discusses these results in relation to what
      screening is, when to screen and the barriers to screening. Despite the majority
      of IMPACT respondents being in favour of screening for AD, the evidence to
      support the introduction of population screening for cognitive impairment is not
      available; however, the importance of optimal identification of AD and other
      dementias in primary care should be a priority for community health professionals
      and payors. In order to do this effectively, further work is required to identify
      good assessment guidelines for use during opportunistic screening for cognitive
      impairment in primary care.

PMID- 20818472
TI  - Physicians and caregivers: ready and waiting for increased participation in
      clinical research.
AB  - Progressive development of pharmacotherapy for Alzheimer's disease (AD) as well
      as non-pharmacological treatments is critically dependent on the timely
      recruitment of appropriate subjects for clinical trials. Accordingly, the IMPACT
      survey sought to determine the level of awareness of clinical trials and the
      willingness to foster patient involvement/participation in research studies.
      IMPACT survey participants were recruited via the Internet in equal numbers from
      5 European countries-France, Germany, Italy, Spain and the United Kingdom. During
      April and May 2009, 250 caregivers and 500 physicians who agreed to participate
      in this market-based survey completed a 30-minute Web-based questionnaire that
      included items concerning awareness of clinical research and willingness to
      facilitate participation of AD patients in such research. Awareness of local
      clinical trials amongst both caregivers (24% overall; range by country, 14% to
      34%) and physicians (19% overall; range by country, 13% to 30%) was found to be
      low in all countries surveyed. In contrast, the willingness of physicians to
      refer patients to, and caregivers to support their participation in, clinical
      trials was extremely high (98% and 81%, respectively). These results strongly
      indicate that physicians and caregivers are ready and waiting to become more
      involved in clinical research. Initiatives to increase awareness of clinical
      trials amongst caregivers and physicians and to conduct clinical trials within
      the geographical area of as many potential participants as possible should result
      in much more effective patient recruitment to AD clinical trials.

PMID- 20818473
TI  - Ornithine alpha-ketoglutarate: could it be a new therapeutic option for
      sarcopenia?
AB  - Our current knowledge on the causes of sarcopenia is still fragmentary. One of
      the most evident candidates to explain muscle loss in elderly includes imbalance
      in protein turnover, i.e. decreased muscle protein synthesis rate, notably in the
      post-prandial state. Nutritional strategies such as leucine supplementation, use
      of fast digested proteins or a pulse protein intake have been show to enhance the
      synthesis rate of muscle proteins in older individuals. Ornithine alpha
      ketoglutarate (OKG) is a precursor of amino acids such as glutamine, arginine and
      proline, and increases the secretion of anabolic hormones, i.e. insulin and
      growth hormone. A beneficial anabolic action of OKG has been demonstrate in
      several pathological conditions associated with muscle loss. Therefore, OKG may
      be of a potential interest to modulate muscle protein metabolism and to maintain
      muscle mass during aging.

PMID- 20818474
TI  - Effects of branched amino acids supplementation in malnourished elderly with
      catabolic status.
AB  - BACKGROUND: Among various nutrients branched amino acids (BCAAS) have been shown
      to be the most responsible for the stimulation of protein synthesis in various
      situations including catabolic states. OBJECTIVES: We evaluated the effect of a
      small amount of proteins enriched with BCAAs (0.4 g/kg/day and 0.2 g/kg/day
      BCAAs) on body weight and composition; nitrogen balance, energy intake and
      inflammation after 2 weeks of supplementation in acute elderly with catabolic
      status. DESIGN: Two weeks randomized controlled trial. SETTING: Geriatric
      department of teaching hospital. SUBJECTS: Thirty patients with malnutrition and
      inflammatory process (MNA < 24, albumin < 30 g/l and CRP > or = 20 mg/l) who
      agreed to participate in the study were consecutively included. METHODS: Body
      composition was determined by labelled water dilution method; resting energy
      expenditure (REE) was determined by indirect calorimetry; energy intake was
      calculated for a 3 days period at D1 and D12. Nutritional and inflammatory
      proteins and cytokines (IL-6 and TNF) were measured at day 1 and 14. RESULTS: No
      difference was observed at day 14 between supplemented (S) and control (C) group
      for weight (S: 58.0 +/- 11.8 kg and C: 60.0 +/- 15.9 kg); fat free mass (S: 40.7
      +/- 8.3 kg and C: 40 +/- 8.2 kg); nitrogen balance (S: 1.34 +/- 2.21 g/day and C:
      0.59 +/- 4.47 g/day); and energy intake (S: 20 +/- 3.6 kcal/day and C: 20.5 +/-
      8.6 kcal/day). Energy intake was at similar level than REE and clearly less than
      energy requirement in C and S. A significant decrease was observed for
      orosomucoid and Prognostic Inflammatory and Nutritional Index (PINI) in S.
      CONCLUSION: Our results do not confirm improvement of nutritional status with
      enriched BCAAs supplementation as suggested in the literature. Persistence of
      inflammatory condition may be an explanation despite an improvement of
      inflammatory status was observed in the supplemented group. Those results show
      clearly that energy requirements are not covered in acute hospitalized elderly
      people. The fact that not only energy intake but also REE are decreased brings a
      new insight on catabolic situations.

PMID- 20818476
TI  - Balance and walking speed predict subsequent 8-year mortality independently of
      current and intermediate events in well-functioning women aged 75 years and
      older.
AB  - BACKGROUND: Physical performance may predict survival independently of other
      current predictors in non selected elderly subjects. We determined if poor
      balance and decreased gait speed may predict mortality after adjustment for both
      baseline and follow-up confounders in well-functioning elderly women. METHODS: A
      subgroup of participants in the Epidemiology of osteoporosis (EPIDOS) study (N =
      1,300) was followed for 8 years. Participants were community-dwelling women aged
      75 or older able to go outside home without assistance. The baseline examination
      included a questionnaire and a clinical and functional examination. Participants
      were contacted every year thereafter by mail. RESULTS: Poor balance, defined by
      the inability to stand in a tandem position or to complete ten foot taps in less
      than 4.6 seconds, and poor mobility, defined by a gait speed of less than 0.80
      m/s or a stride length of less than 0.5 m were significant predictors of low 8
      year survival, independently of other predictors of death at baseline
      (educational level, social network, number of drugs, fear of falling, visual
      acuity, perceived health, IADL score, physical activity, and comorbidities) and
      during follow-up (falls, IADL score, the need to be accompanied to go outside,
      weight loss, hospitalization, and the report of new comorbidities). CONCLUSION:
      The current study shows that poor balance and mobility are significant predictors
      of 8-year mortality independently of baseline and intermediate events in pre
      disabled women aged 75 years and older, suggesting that they may reflect a
      certain failure to respond adequately in the face of present and future medical
      and non-medical events.

PMID- 20818475
TI  - Clinical practice in nursing homes as a key for progress.
AB  - With the aging of the world's population there has become a major need for the
      development of nursing homes throughout the world. While some countries provide
      high quality care for the disabled elderly, in others this is not the case.
      Education of a medical director has been shown to improve the quality of the
      nursing home. Physicians need to have knowledge of how to implement continuous
      quality improvement and culture change. Key medical issues include moving to a
      restraint free environment, subsyndromal delirium, behavioral disturbances,
      weight loss, pain management, pressure ulcers, falls, hip fractures,
      polypharmacy, depression and frailty.

PMID- 20818477
TI  - Falls' and fallers' profiles.
AB  - OBJECTIVE: To describe the different falls typology and to investigate whether
      different falls profiles and faller profiles could be identified among a cohort
      of community-dwelling women aged 75 years and older. DESIGN: Prospective cohort
      study. PARTICIPANTS: Women aged 75 years and older were enrolled in five French
      centers after a random selection from electoral lists and included in the EPIDOS
      study. MEASUREMENTS: During a 4 year follow-up, women were contacted by telephone
      every 4 months to investigate the occurrence of falls. To minimize the memory
      bias, the specific questionnaire on falls was completed only if the fall took
      place in the week preceding the contact. A multiple correspondence analysis
      followed by clustering was carried out to identify the typology of falls.
      RESULTS: 727 women described at least one fall. A full description of 662 falls
      was obtained during the follow-up period. In the multiple correspondence analysis
      the main discriminant item was outside versus inside falls. Moreover, four
      clusters were showed: outside falls linked to lack of attention (28% of women),
      outside falls related to exogenous/environmental factors (16%), inside falls
      associated with frailty (44%) and in height falls (11%). We also found that each
      type of falls was correlated with particular health or functional status
      (i.e.;dependence, motion difficulty, weakness, use of walking aid, ...).
      CONCLUSION: From frailty to hyperactivity there are different falls and fallers
      profiles. Assessing such fall profiles could be helpful to develop new dedicated
      fall prevention programs in the elderly.

PMID- 20818478
TI  - Open letter: the need to change the method for defining mild airway obstruction.

PMID- 20818479
TI  - Paradoxes of spirometry results, and smoking cessation.

PMID- 20818480
TI  - The effect of bright light on sleepiness among rapid-rotating 12-hour shift
      workers.
AB  - OBJECTIVE: About 20% of workers in industrialized countries are shift workers and
      more than half of them work on night or rotating shifts. Most night workers
      complain of sleepiness due to lack of adjustment of the circadian rhythm. In
      simulated night-work experiments, scheduled exposure to bright light has been
      shown to reduce these complaints. Our study assessed the effects of bright light
      exposure on sleepiness during night work in an industrial setting. METHODS: In a
      cross-over design, 94 workers at a ceramic factory were exposed to either bright
      (2500 lux) or normal light (300 lux) during breaks on night shifts. We initiated
      20-minute breaks between 24.00 and 02.00 hours. Sleepiness ratings were
      determined using the Stanford Sleepiness Scale at 22.00, 24.00, 02.00 and 04.00
      hours. RESULTS: Under normal light conditions, sleepiness peaked at 02:00 hours.
      A significant reduction (22% compared to normal light conditions) in sleepiness
      was observed after workers were exposed to bright light. CONCLUSION: Exposure to
      bright light may be effective in reducing sleepiness among night workers.

PMID- 20818481
TI  - Evaluation of curcumin acetates and amino acid conjugates as proteasome
      inhibitors.
AB  - Curcumin (diferuloylmethane) is the main active ingredient of turmeric, a
      traditional herbal medicine and food of south Asia. Curcumin has been found to
      have a wide range of biological activities, including antioxidant, anti
      inflammatory, chemopreventive and chemotherapeutic activities. Curcumin is
      currently being tested in clinical trials for treatment of various types of
      cancers, including multiple myeloma, pancreatic cancer and colon cancer. Although
      no toxicity associated with curcumin (even at very high doses) has been observed,
      the effects of curcumin in other solid tumors have been modest, primarily due to
      poor water solubility and poor bioavailability in tissues remote from the
      gastrointestinal tract. Therefore, there is a need for the discovery of curcumin
      analogs with better water solubility or greater bioavailability for the treatment
      of solid tumors such as prostate cancer. In this study, curcumin acetates and
      amino acid conjugates of curcumin were studied in terms of their proteasome
      inhibitory and antiproliferative effects against several human cancer cell lines.
      It was found that the water soluble amino acid conjugates of curcumin showed a
      potent antiproliferative effect and are potent proteasome inhibitors. Docking
      studies of the curcumin amino acid conjugates for proteasome inhibition were
      carried out to explain their biological activities. It is suggested that they may
      serve as the water soluble analogs of curcumin.

PMID- 20818482
TI  - Biological effects of inorganic arsenic on primary cultures of rat astrocytes.
AB  - It is well established that inorganic arsenic induces neurotoxic effects and
      neurological defects in humans and laboratory animals. The cellular and molecular
      mechanisms of its actions, however, remain elusive. Herein we report the effects
      of arsenite (NaAsO2) on primary cultures of rat astrocytes. Cells underwent
      induction of heat shock protein 70 only at the highest doses of inorganic arsenic
      (30 and 60 microM), suggesting a high threshold to respond to stress. We also
      investigated arsenic genotoxicity with the comet assay. Interestingly, although
      cells treated with 10 microM arsenite for 24 h maintained >70% viability, with
      respect to untreated cells, high DNA damage was already observed. Since arsenic
      is not known to be a direct-acting genotoxic agent, we investigated the
      possibility that its effects are due, in astrocytes as well, to ROS formation, as
      already described for other cell types. However, FACS analysis after CM-H2DCFDA
      staining did not evidence any significant increase of ROS production while, on
      the contrary, at the highest arsenite concentrations used, ROS production
      decreased. Concordantly, we found that, if most cells in the culture are still
      alive (i.e. up to 10 microM arsenite), they show a treatment-dependent increase
      in the concentration of SOD1. On the other hand, SOD2 concentration did not
      change. Finally, we found that astrocytes also synthesize PIPPin, an RNA-binding
      protein, the concentration of which was recently reported to change in response
      to stress induced by cadmium. Here we also report that, in cells exposed to high
      doses of arsenite, an anti-PIPPin antibody-positive faster migrating protein
      appears.

PMID- 20818483
TI  - UVB radiation induces an increase in intracellular zinc in human epidermal
      keratinocytes.
AB  - Ultraviolet (UV) radiation is known to cause oxidative stress, inflammation, DNA
      damage and apoptotic cell death; however, many details of these malign mechanism
      have yet to be elucidated. In this study, the exposure of adult human epidermal
      keratinocytes (HEKa) with UVB (>100 mJ/cm(2)) resulted in the significant
      increase of intracellular zinc that was released from its storage and was
      detected by fluorescent zinc indicators. Toxicity testing revealed that UVB
      induced zinc release in HEKa is associated with HEKa cell death. Cells that
      showed elevated intracellular zinc fluorescence upon UVB exposure were also
      stained by propidium iodide (PI), a traditional viability indicator whose
      fluorescent signal is as a result of its intercalating with DNA fragments and is
      unaffected by zinc concentration, showing significant colocalization [Pearson's
      correlation coefficients r=0.956 (n=6)]. The cytotoxicity of zinc was also
      determined by an MTT assay after applying the exogenous zinc (ZnCl2) along with
      its ionophore pyrithione (20 microM) into HEKa culture medium. A significant
      reduction in cell viability as a function of both zinc concentration and exposure
      time was observed. The treatments of 1, 10 and 100 microM ZnCl2 with pyrithione
      demonstrated 2.3, 60 and 84% cell deaths, respectively (control 0.5%) after 30
      min. ZnCl2 (100 microM) was also found to induce complete HEKa death after 1 h.
      Thus, the present study demonstrates that UVB irradiation-induced increased zinc
      is detrimental to HEKa viability, and zinc may be a necessary step in UVB-induced
      cell death signaling pathways.

PMID- 20818484
TI  - Oxidative stress parameters in paediatric non-alcoholic fatty liver disease.
AB  - We have investigated the presence and the possible clinical implications of
      oxidative stress in children with non-alcoholic fatty liver disease (NAFLD). The
      present study was an observational study of oxidative stress parameters in the
      progression of paediatric NAFLD. We observed the role of oxidative stress in
      children diagnosed with NAFLD by evaluating: serum protein carbonyls, hepatic
      expression of 8-hydroxy-2-deoxyguanosine (8-OHG), and circulating antibody
      against malondialdehyde adducted human serum albumin (MDA-HSA). Forty consecutive
      children with biopsy-proven NAFLD (27 male; 13 female) referred to Bambino Gesu
      Children's Hospital, Rome, Italy, from January 2007 to April 2008 were included
      in the study. Serum variations of protein carbonyls, 8-OHG, and circulating
      antibody against MDA-HSA were evaluated. Elevated protein carbonyls were evident
      in 33 subjects (83%) irrespective of obesity and insulin resistance. Moreover,
      liver biopsies of NAFLD patients positive for circulating protein carbonyls also
      showed a significant increase in the nuclear staining for 8-OHG (p=0.006; 95% CI
      3.1-17.7). Anti-MDA-HSA IgG above control threshold was detected in 25 (63%)
      children. Although protein carbonyl levels were unrelated with disease severity,
      patients with elevated anti-MDA-HSA IgG had scores for lobular inflammation
      significantly higher (p=0.019) than subjects with antibodies within the control
      range, while steatosis, hepatocyte ballooning and fibrosis were similar. High
      anti-MDA-HSA reactivity was also associated with a 13-fold increased risk
      (OR=12.9; 95= CI 1.5-113.8; p=0.013) of a NAFLD activity score (NAS) >or=5. These
      results demonstrate that oxidative stress has an high prevalence in children with
      NAFLD and is associated with an increased severity of steatohepatitis.

PMID- 20818485
TI  - Prevention and regression of non-alcoholic steatohepatitis (NASH) in a rat model
      by metabosartan, telmisartan.
AB  - The favorable metabolic effects of telmisartan have been attributed to its
      angiotensin II receptor blockade and action as a partial agonist of peroxisome
      proliferator-activated receptor (PPAR)-gamma. We previously reported that
      administration of telmisartan markedly inhibited lipid accumulation in the liver
      in mice fed a high-fat diet. In the present study, we further examined the
      protective effect of telmisartan in a non-alcoholic steatohepatitis (NASH) model
      induced by feeding Wistar rats an L-methionine- and choline-deficient (MCA) diet.
      In the first experiment, rats were fed an MCA diet for 8 weeks with or without
      telmisartan (3 mg/kg/day). Liver fibrosis was observed by Masson trichrome
      staining, and co-treatment was shown to attenuate liver fibrosis. In the second
      experiment, Wistar rats were fed an MCA diet for 20 weeks, and telmisartan (3
      mg/kg/day) was administered during weeks 0-20 as a preventive model or weeks 8-20
      as a therapeutic model. As a result, telmisartan administration in both models
      significantly attenuated liver fibrosis and an increase in serum AST. Of
      importance, the HGF concentration in the liver was significantly increased in the
      telmisartan-treated group. Overall, telmisartan showed a potential action to
      improve NASH induced by an MCA diet, possibly due to increased HGF production
      through partial agonist of PPAR-gamma. These favorable characteristics of
      telmisartan as a partial agonist of PPAR-gamma may provide a benefit in the
      treatment of metabolic syndrome beyond its blood pressure-lowering effect.

PMID- 20818486
TI  - Identification of the novel protein FAM172A, and its up-regulation by high
      glucose in human aortic smooth muscle cells.
AB  - The family with sequence similarity 172, member A (FAM172A) is a hypothetical
      protein. We recently cloned the FAM172A gene from normal human aortic tissues. In
      a previous study we also showed that the FAM172A gene was up-regulated by high
      glucose levels in macrophages. In the present study, we further identified the
      FAM172A protein at the level of translation and studied the effects of high
      glucose levels on its expression in human aortic smooth muscle cells. The FAM172A
      gene was subcloned into the eukaryotic expression vectors, PDC315 and pEGFP-N2.
      The cloned sequence shows an open reading frame of 1251 nucleotides encoding a
      protein of 416 amino acids. We further expressed the recombinant FAM172A protein
      and generated rabbit anti-human FAM172A polyclonal antibodies. The FAM172A
      protein was identified for the first time at the translation level by Western
      blot analysis. Western blotting also demonstrated that the FAM172A protein could
      be detected in human aortic endothelial, human aortic smooth muscle cells and THP
      1-derived macrophages, the highest expression being observed in the human aortic
      smooth muscle cells. By a combination of bioinformatics and confocal laser
      scanning microscopy, we found that the FAM172A protein in HEK293 cells, was
      mainly located in the nucleus, and that there was an Arb2 conserved domain in the
      FAM172A protein sequence. We also presented evidence that the FAM172 protein
      expression in human aortic smooth muscle cells was up-regulated by high glucose
      levels in a concentration-dependent and time-course manner. We speculated that as
      a novel protein, FAM172A could be involved in the pathogenesis of high glucose
      induced vascular damage.

PMID- 20818487
TI  - Synthesis and characterization of a novel cationic polymer gene delivery vector.
AB  - Non-viral vectors have been widely used in gene transfection. However, its
      drawbacks limit its applications. In this study, a novel cationic polymer was
      developed as a DNA condensing agent for systemic gene delivery. Its transfection
      efficiency, cytotoxicity, and biocompatibility were also evaluated. Sofast, novel
      cationic polymer of branched polyethlenimine, was constructed by chemical
      methods. Its diameter, zeta potential, nucleic acid binding ability, and anti
      nuclease ability were detected by electron microscopy and gel electrophoresis. In
      vitro, the efficiency of transfection was measured by comparing it with other
      gene vectors in different cell lines. MTT assay was performed to determine
      cytotoxicity. The compatibility of Sofast gene vector in the serum and its
      stability were investigated. Mouse, guinea pig and rabbit were used to process
      the toxic, allergenic, and pyrogenic properties of the vector in vivo. The in
      vivo expression was performed in the guinea pig. The results from an in vitro
      assay proved that the Sofast gene vector had a higher transfection efficiency
      than other gene vectors in a variety of primary cell cultures and transformed
      cell lines. The cytotoxicity assay showed a lower cytotoxicity and the cellular
      survival rate was >90%. The Sofast gene vector possessed compatibility with the
      serum and was fit to be transported at normal temperature. The results from in
      vivo tests indicated that the Sofast gene vector had greatly lower cytotoxicity,
      better biocompatibility, and higher transfection efficiency compared with other
      gene vectors. Because the Sofast gene vector had higher transfection efficiency,
      lower cytotoxicity and better compatibility than other gene vectors, it could be
      used for gene transfection both in vitro and in vivo.

PMID- 20818488
TI  - Systemic or topical application of plasminogen activator inhibitor with extended
      half-life (VLHL PAI-1) reduces bleeding time and total blood loss.
AB  - Civilian and military trauma patients consist of a disproportional number of
      young people, causing a considerable burden to society in terms of disability and
      premature death. Hemorrhage is a leading cause of mortality in this group of
      patients and the novel methods to reduce bleeding would be welcomed. Management
      of bleeding following major trauma includes hemostatic agents that offer
      effective clotting. However a very limited number of agents control secondary
      bleeding triggered by lysis of the clot. Fibrinolysis depends on the balance
      between tissue plasminogen activator (tPA), activating plasminogen to plasmin
      initiating fibrinolysis, and plasminogen activator inhibitor type 1 (PAI-1)
      inhibiting tPA and preventing lysis. The drugs available on the market that
      prevent the activation of plasminogen have been used successfully, but have some
      side effects and limited efficacy for the control of localized bleeding in the
      surgical setting. Inhibitors of tPA, initiator of clot fibrinolysis, have not yet
      found their way into the clinical arena. Plasminogen activator inhibitor-1, the
      major specific inhibitor of tPA, can be used to limit fibrinolysis.
      Unfortunately, PAI-1 has a short half-life of approximately 2 h and is rapidly
      converted to the latent form. A recombinant PAI-1 with very long half-life
      developed in our laboratory (a two-point mutant, VLHL PAI-1, half-life over 700
      h) has clinical potential as an agent to promote hemostasis in several scenarios
      including surgical injury, trauma, and PAI-1 deficiency. Here we report testing
      of VLHL PAI-1 as a potent inactivator of fibrinolysis reducing total blood loss
      while applied systemically or topically in experimental animals. The very long
      half-life of VLHL PAI-1 may provide an advantage in the important physiological
      mechanism to protect clots from premature dissolution, when applied topically or
      systemically to prevent excessive bleeding in the surgical and trauma setting and
      possibly in PAI-1 deficient patients.

PMID- 20818489
TI  - Expression and localization of prominin-1 in isoproterenol-treated rat parotid
      gland.
AB  - Prominin-1 (CD133) is a pentaspan cholesterol-binding membrane glycoprotein.
      Chronic treatment with isoproterenol, a beta-receptor agonist, induces several
      dramatic effects on salivary glands, such as enhanced DNA synthesis and
      proliferation of salivary acinar cells. In addition, the biosynthetic pathways of
      membrane lipids may be altered by the isoproterenol stimulation. The purpose of
      this study was to investigate the effect of isoproterenol administration on
      prominin-1 expression profiles in rat parotid gland by means of PCR and
      immunohistochemistry. Rats were chronically treated with the beta-adrenergic
      agonist for 1, 3, and 7 days. Our results showed that isoproterenol-treatment
      caused a down-regulation of prominin-1 on day 3 and 7 of treatment, as well as a
      differential immunostaining distribution pattern. This study suggests that
      isoproterenol-treatment may represent a useful tool to explore the molecular
      mechanisms involved in the synthesis and release of prominin-1. Such efforts
      could contribute to the development of diagnostic tools based on the detection of
      prominin-1 in biological fluids, such as saliva.

PMID- 20818490
TI  - Fever temperature enhances mechanisms of survival of Streptococcus agalactiae
      within human endothelial cells.
AB  - Group B streptococci (GBS) are the most common cause of pneumonia and sepsis
      during the neonatal period. However, the pathogenesis of invasive infection is
      poorly understood. We investigated the ability of GBS grown at 37 degrees C and
      40 degrees C to adhere and invade human umbilical vein endothelial cells (HUVECs)
      at different periods of incubation (0, 0.5, 1, 2, 18 and 24 h). All strains
      tested, except strain 88641-vagina survived for 24 h in the intracellular
      environment at 40 degrees C. For serotype III grown at 40 degrees C, both strains
      (80340-vagina and 90356-liquor) showed increased adherence and intracellular
      survival when compared to bacteria grown at 37 degrees C (P<0.01). GBS serotype V
      strains (88641-vagina and 90186-blood) showed ability to survive inside HUVECs
      until 2 and 24 h post-infection at 40 degrees C and 37 degrees C, respectively
      (P<0.01). Influence of growth temperature in bacterial interaction with
      endothelial cells was partially dependent of serotypes and the clinical origin of
      strains. Serotypes III and V strains grown at both temperatures remained viable
      within acidic endothelial vacuoles which acquired Rab7 and LAMP-1 endosomal
      markers. The data emphasize the influence of temperature on cellular events of
      phagocytosis and pathogenesis of GBS diseases.

PMID- 20818491
TI  - Repair of orbital wall defects using biocoral scaffolds combined with bone marrow
      stem cells enhanced by human bone morphogenetic protein-2 in a canine model.
AB  - Repair of orbital bone defects caused by trauma, infection or cancer is a
      continuous challenge in reconstructive surgery. Few studies have reported the
      application of tissue engineering for the repair of orbital bone defects in large
      animal models. Thus, we investigated the effects of tissue-engineered bone
      enhanced by the human bone morphogenetic protein-2 (BMP2) on the repair of
      orbital wall defects in a canine model. Autologous bone marrow stromal cells
      (BMSCs) from 16 Beagle dogs were isolated and cultured in vitro. Passage 2 cells
      were transfected with adenovirus containing human BMP2 (adv-BMP2) and tissue
      engineered bone was constructed using BMP2-expressing BMSCs seeded on a biocoral
      scaffold. Circular defects (12-mm diameter) created bilaterally in the canine
      medial orbital wall, were treated with one of the following: adv-BMP2-transfected
      BMSC/coral composite (group I, n=8), BMSC/coral composite (group II, n=8),
      biocoral alone (group III, n=8), or were left untreated (group IV, n=8). Four
      samples from each group were harvested at 12 and 24 weeks after surgery, and the
      volume and density of newly regenerated bone were determined by micro-computed
      tomographic (micro-CT) measurement. The rate of new bone deposition and
      regeneration was measured by tetracycline/calcein labeling and histomorphometric
      analysis. The results showed that a canine 12-mm circular orbital defect was a
      critical-sized defect, and the micro-CT and histomorphometry detection results
      indicated that the combined delivery of BMSCs and BMP2 (group I) resulted in the
      highest regenerative effects on orbital bone defects, compared to the other
      groups without BMP2. Biocoral scaffolds combined with BMSCs enhanced by BMP2
      could improve the healing of critical-sized medial orbital wall defects in
      canines.

PMID- 20818492
TI  - Enhancement of phagocytotic activity by prion protein in PrP-deficient macrophage
      cells.
AB  - Macrophages, especially follicular dendritic cells, contribute to the
      pathogenesis of prion diseases by accumulating an abnormal isoform of prion
      protein (PrPSc), which is converted from the cellular isoform of prion protein
      (PrPC). As information on the function of PrPC in macrophages is limited, we have
      established a prion protein (PrP) gene (Prnp)-deficient macrophage cell line from
      the bone marrow of ZrchI Prnp-/- mice. These cells expressed macrophage specific
      proteins (F4/80 and MOMA-2) and displayed phagocytotic properties. The Prnp-/-
      macrophage cell line (MplZ) showed shorter pseudopodium extension and less
      phagocytotic activity than a Prnp+/+ macrophage cell line (MWF). In addition, the
      MplZ cells were more sensitive to serum deprivation than the MWF cells and
      underwent apoptotic cell death in these conditions. These findings suggest that
      PrPC enhances the incorporation of materials possibly including PrPSc and
      decreases the sensitivity of cells to oxidative stress, which may be induced by
      PrPSc accumulation.

PMID- 20818493
TI  - The endocytic penetration mechanism of iron oxide magnetic nanoparticles with
      positively charged cover: a morphological approach.
AB  - In this study we present a morphological approach in observing the interaction of
      cationic magnetic nanoparticles with A-549 cells (human lung adenocarcinoma).
      Under our experimental conditions, nanoparticles easily penetrated cells and were
      observed in vivo, using bright light microscopy. In fixed cells, nanoparticles
      remained inside cells, showing quantity and distribution patterns similar to
      those in unfixed cells. The presence of nanoparticles did not affect cell
      viability or the morphologic parameters assessed. We determined the potential
      internalization mechanism of nanoparticles into cells using endocytosis
      inhibitors. The results suggest that nanoparticles used in this study penetrate A
      549 cells mainly through a macropinocytosis process.

PMID- 20818494
TI  - The effects of atorvastatin on pulmonary arterial hypertension and expression of
      p38, p27, and Jab1 in rats.
AB  - Statins have recently come under evaluation for the treatment of pulmonary
      arterial hypertension (PAH). The aim of this study was to examine the effects of
      atorvastatin on the clinical manifestations and expression of p38, p27 and Jab1
      using a rat PAH model. Ninety-six male Wistar rats were divided into control
      (receiving no surgical treatment), vehicle and treatment groups, among which the
      last two groups underwent left pneumonectomy and were then treated with
      monocrotaline (MCT, 60 mg/kg). Both control and vehicle groups subsequently
      received saline, and the treatment group received atorvastatin (20 mg/kg) by
      stomach catheter. Rats were sacrificed, and mean pulmonary arterial pressure
      (mPAP) and right ventricle hypertrophy index (RVHI) were measured. The expression
      of p38, p27, and Jab1 was evaluated by immunohistochemistry and Western blotting.
      At 28 days, mPAP and RVHI and expression levels of Jab1 and p38 in the vehicle
      group were significantly higher than those in the treatment and control groups.
      However, the expression of p27 was lowest in the vehicle group among the three
      groups. Atorvastatin reduced PAP and RVHI in the rat PAH model, decreased
      expression of p38 and Jab1 but increased expression of p27.

PMID- 20818495
TI  - Changes in factor VII-activating protease in a bleomycin-induced lung injury rat
      model and its influence on human pulmonary fibroblasts in vitro.
AB  - Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are
      characterized by non-cardiogenic pulmonary edema, respiratory distress and
      hypoxemia. Factor VII-activating protease (FSAP) is a plasma-derived protease
      which inhibits the proliferation and migration of hepatic stellate cells and
      vascular smooth muscle cells. This study was designed to determine the dynamic
      expression changes in FSAP in a bleomycin-induced pulmonary fibrosis rat model
      and the influence of FSAP on human pulmonary fibroblasts (HPF). The expression of
      FSAP was examined in a rat model of bleomycin-induced pulmonary fibrosis by
      immunohistochemical staining, quantitative real-time RT-PCR and Western blot
      analysis. The influence of FSAP on cell proliferation and migration of HPF was
      investigated by the BrdU incorporation assay and transwell cell culture chambers,
      respectively. The effect of FSAP on platelet-derived growth factor (PDGF)
      stimulated p42/p44 mitogen-activated protein kinase (MAPK) activation on HPF was
      determined by Western blot analysis. FSAP was observed prominently in alveolar
      epithelial cells as well as microvascular endothelial cells of the lung
      parenchyma and was markedly increased at the early phase of bleomycin-induced
      pulmonary fibrosis, but decreased at the late stage, particularly during the
      pulmonary fibrosis. FSAP inhibited PDGF-stimulated proliferation, migration,
      p42/p44 MAPK phosphorylation and collagen III synthesis of the HPF. We concluded
      that epithelial cells in lungs represent a source of FSAP at the early stage in
      acutely injured lung. Moreover, we demonstrated an inhibitory effect of FSAP on
      PDGF-stimulated proliferation and migration of HPF in vitro, suggesting that FSAP
      may modulate inflammation and exert a beneficial effect on ARDS.

PMID- 20818496
TI  - Osteoclast activation by receptor activator of NF-kappaB ligand enhances the
      mobilization of hematopoietic progenitor cells from the bone marrow in acute
      injury.
AB  - Osteoclasts (OCLs) are multinucleated cells that are derived from the
      monocyte/macrophage hematopoietic lineage in response to receptor activator of NF
      kappaB ligand (RANKL) activation. They are specialized cells responsible for
      physiological bone resorption and as well as pathologic bone loss. In addition to
      their unique ability to resorb bone, OCLs also play a potential role in the
      mobilization of hematopoietic progenitor cells from the bone marrow (BM),
      particularly under various stress stimuli (e.g. hypoxia, injury or inflammation).
      We investigated the effect of activated OCLs on the stem cell niche and whether
      this leads to mobilization of hematopoietic progenitors. We induced activated
      OCLs from the RAW264.7 cell line through stimulation with RANKL and we quantified
      the levels of the stem cell niche component SDF-1 on the osteblasts and CXCR4 on
      the bone marrow cells (BMCs) by culturing with supernatants from activated OCLs.
      In addition, we exposed mice to stress by inducing liver injury with CCl4
      followed by injecting RANKL to activate OCLs and compared the effect on the
      mobilization of hematopoietic progenitor cells from the BM. We found that
      functional OCLs cleaved SDF-1alpha in the osteoblasts and increased CXCR4
      expression in the BMCs. Moreover, under stress in vivo, mobilized hematopoietic
      progenitor cells were significantly increased after RANKL treatment. These
      results suggest that OCLs might be involved in alteration of the interaction
      between SDF-1 and CXCR4 leading to mobilization of hematopoietic progenitor cells
      from the BM.

PMID- 20818497
TI  - Ursolic acid inhibits early lesions of diabetic nephropathy.
AB  - The present study sought to investigate the effects of ursolic acid (UA) on the
      development of glomerular hypertrophy and type IV collagen accumulation, two
      early lesions associated with diabetic nephropathy (DN). By treating
      streptozotocin (STZ)-induced diabetic mice with low-dose UA (0.01% in food) for
      three months, the diabetes-induced glomerular hypertrophy and type IV collagen
      accumulation in the kidneys were found to be markedly ameliorated. Further
      studies identified that UA treatment suppressed diabetes-induced activations of
      STAT-3, ERK1/2 and JNK pathways, but not the diabetes-induced activation of the
      p38 pathway. Furthermore, diabetes-induced overexpression of iNOS in the renal
      cortex was also significantly suppressed by the treatment. UA may thus be
      considered as a potential therapeutic agent in treating DN.

PMID- 20818498
TI  - Role of cross-talk between the Smad2 and MAPK pathways in TGF-beta1-induced
      collagen IV expression in mesangial cells.
AB  - Transforming growth factor beta1 (TGF-beta1) can promote sclerosis in many kidney
      diseases by enhancing the synthesis of collagens. However, the mechanisms of down
      stream intracellular signal transduction in TGF-beta1-induced collagen synthesis
      is not fully understood. The purpose of this study was to further investigate the
      mechanisms and the cross-talk between the MAPK and Smad2 pathways. We found that
      U0126, a specific inhibitor of ERK1/2, and SB203580, a specific inhibitor of p38,
      down-regulated the TGF-beta1-induced phosphorylation of Smad2 at both linker and
      C-terminal sites in rat mesangial cells. Whereas, SP600125, a specific inhibitor
      of JNK, only down-regulated the phosphorylation of Smad2 at the C-terminal sites,
      but had little effect on the phosphorylation of Smad2 at linker sites. However,
      all three MAPK inhibitors reduced collagen IV synthesis induced by TGF-beta1.
      Furthermore, TGF-beta1 induced the phosphorylation of Smad2 at both the linker
      and C-terminal sites. Transient transfection of a dominant negative Smad2
      construct significantly decreased TGF-beta1-induced phosphorylation of ERK1/2,
      JNK and expression of collagen IV, but did not decrease the phosphorylation of
      p38. These findings demonstrate that there is cross-talk between the MAPK
      (ERK1/2, JNK, p38) and Smad2 pathways, and that the cross-talk interacts mutually
      to enhance the synthesis of collagen IV in rat mesangial cells.

PMID- 20818499
TI  - Hypoxia and reoxygenation of primary human hepatocytes induce proteome changes of
      glucose metabolism, oxidative protection and peroxisomal function.
AB  - Protective hepatocellular responses to a hypoxic challenge are crucial to
      preserve liver function. The knowledge of affected metabolic functions could help
      assess and enhance hepatic ischemic tolerance. Here we studied adaptive
      mechanisms in human hepatocytes after hypoxia and reoxygenation using a proteomic
      approach. Proteins from primary hepatocytes were extracted after 6 h of hypoxia
      and 24 h of reoxygenation. The proteome was analyzed by 2D-electrophoresis.
      Densitometry and mass spectrometry (MALDI-TOF-MS) were used for protein
      identification. Two hundred and sixty-two spots were differentially analyzed and
      33 spots displayed significant differences between hypoxic and normoxic cells.
      Seventeen proteins were identified by mass spectrometry. After hypoxia and
      reoxygenation the UTP-glucose-1-phosphate uridyltransferase, phosphoglycerate
      kinase1, fructose-1,6-bisphosphate aldolase, glyceraldehyde-3-phosphate
      dehydrogenase, fructose-1,6-bisphosphatase, thiosulfat-sulfurtransferase,
      thioredoxin peroxidase, peroxiredoxin III, and annexin A2 proteins were down
      regulated. An increased expression was found for carbamoyl phosphate synthetase
      I, heat shock 70 kDa protein5, phosphoenolpyruvate carboxy-kinase, catalase
      isoform2, peroxiredoxin II, glutathione S-transferase, hydroxyacid oxidase1, and
      F1-ATP synthase, alpha subunit1. Hepatocellular adaptation to hypoxia and
      reoxygenation involve glucose metabolism, peroxisomal functions, and oxidative
      stress protection. The identified proteins can serve as possible diagnostic
      targets to monitor hepatic hypoxic tolerance e.g. in the context of liver surgery
      and transplantation.

PMID- 20818500
TI  - Frequency and diversity of human immunodeficiency virus type 1 mutations
      associated with antiretroviral resistance among patients from Southern Brazil
      failing highly active antiretroviral therapy (HAART).
AB  - The human immunodeficiency virus type 1 (HIV-1) epidemic in Brazil is spreading
      to small municipalities as well as the innermost parts of the country and scarce
      information has been reported on the frequency of HIV-1 resistance-associated
      mutations in these areas. To determine the frequency and diversity of the HIV-1
      antiretroviral resistance-associated mutations among patients failing highly
      active antiretroviral therapy from Londrina in Southern Brazil, 127 HIV-1
      genotyping tests that were assayed during January 2000 to July 2008 from 108
      patients were evaluated. Sixty-nine patients (63.9%) were male and 39 (36.1%)
      were female and the age ranged from 10 to 68 years (mean, 40.8+/-9.2). All of
      them showed at least one HIV-1 antiretroviral resistance-associated mutation and
      in 72 (56.7%) genotyping tests, mutations for the three antiretroviral classes
      were detected simultaneously. Mutations associated with resistance to protease
      inhibitor (PI) were detected in 124 tests (97.6%), the main ones were L90M in 28
      (22.0%), V82A in 27 (21.2%), M46I in 26 (20.5%), and I54V in 23 (18.1%). The main
      mutations associated with nucleoside reverse transcriptase inhibitor (NRTI)
      resistance were M184V in 82 (64.6%), and the thymidine analog mutations were D67N
      in 51 (40.1%) tests, K70R in 45 (35.4%), T215Y in 40 (31.5%), and M41L in 38
      (30.0%). The most frequent major mutations associated with resistance to non
      nucleoside RT inhibitors (NNRTI) were K103N in 47 (37.0%), G190A in 11 (8.7%),
      and G190S in 2 (2.6%) tests. Mutations associated with reduced susceptibility to
      NRTI and IP simultaneously were observed in 46 (36.2%) tests. The results
      obtained may contribute to the improvement of the treatment strategies and the
      management of the antiretroviral drug therapy of HIV-1-infected patients from
      this Brazilian region, reducing public costs for antiretroviral drugs which have
      not been efficient in therapy.

PMID- 20818501
TI  - Identification of CYP21A2 mutant alleles in Czech patients with 21-hydroxylase
      deficiency.
AB  - Congenital adrenal hyperplasia (CAH) is comprised of a group of autosomal
      recessive disorders caused by an enzymatic deficiency which impairs the
      biosynthesis of cortisol and, in most of the severe cases, also the biosynthesis
      of aldosterone. Approximately 90-95% of all the CAH cases are due to mutations in
      the steroid 21-hydroxylase gene (CYP21A2). In this study, the molecular genetic
      analysis of CYP21A2 was performed in 267 Czech probands suspected of 21
      hydroxylase deficiency (21OHD). 21OHD was confirmed in 241 probands (2 mutations
      were detected). In 26 probands, a mutation was found only in 1 CYP21A2 allele. A
      set of 30 different mutant alleles was determined. We describe i) mutated CYP21A2
      alleles carrying novel point mutations (p.Thr168Asn, p.Ser169X and p.Pro386Arg),
      ii) mutated CYP21A2 alleles carrying the novel chimeric gene designated as CH-7,
      which was detected in 21.4% of the mutant alleles, iii) an unusual genotype with
      a combination of the CYP21A2 duplication, 2 point mutations and the CYP21A2 large
      scale gene conversion on the second allele, and (iv) a detailed analysis of the
      chimeric CYP21A1P/CYP21A2 genes. In conclusion, our genotyping approach allowed
      for the accurate identification of the CYP21A2 gene mutations in 21OHD patients
      and their families and provided some useful information on diagnosis and genetic
      counselling.

PMID- 20818502
TI  - Connexin40 nonsense mutation in familial atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia
      associated with substantial morbidity and mortality. Genetic variants play
      important roles in the pathogenesis of AF. However, AF is a genetically
      heterogeneous disorder, and the genetic determinants in most patients with AF
      remain to be identified. In this study, the entire coding region of the
      connexin40 gene, encoding the cardiac gap junction membrane channel protein
      alpha5, was sequenced in 126 unrelated probands with familial AF. A novel
      heterozygous mutation, c.145C<T, in connexin40, was identified in a proband. The
      mutation was predicted to introduce a premature stop codon at amino acid position
      49 (p.Q49X). This nonsense mutation was present in all the living relatives of
      the mutation carrier, co-segregating with AF in the family with a penetrance of
      100%. However, it was absent in 200 ethnically matched unrelated control
      individuals. The findings suggest a pathogenic link between the compromised
      connexin40 function and familial AF, hence providing new insight into the
      molecular mechanisms involved in AF.

PMID- 20818503
TI  - Increased expression of the receptor for activation of NF-kappaB and decreased
      runt-related transcription factor 2 expression in bone of rats with
      streptozotocin-induced diabetes.
AB  - Insulin-dependent diabetes mellitus (IDDM) is associated with an increased risk
      of osteopenia/osteoporosis in humans. The effects of IDDM on osteoblastogenesis
      and osteoclastogenesis were investigated using diabetic rats at 2 weeks after the
      streptozotocin (STZ) injection. The weight of the tibia and proximal tibia and
      the amount of hydroxyproline and calcium in the proximal tibia were significantly
      lower in diabetic rats than control rats. Markers of bone formation, alkaline
      phosphatase (ALP) activity and the number of osteoblasts in the proximal tibia
      and the serum osteocalcin level, were significantly lower. Markers of bone
      resorption, activity of tartrate-resistant acid phosphatase (TRAP) and cathepsin
      K and the number of osteoclasts in the proximal tibia and urinary excretion of
      deoxypyridinoline, were higher in diabetic rats than control rats. mRNA levels of
      receptor for activation of NF-kappaB (RANK), c-fos, c-jun, TRAP and cathepsin K
      were significantly increased in diabetic rats, although RANK ligand,
      osteoprotegerin, macrophage colony-stimulating factor and c-fms levels were
      similar to the control value. The decreased expression of ALP, osteoclacin and
      collagen mRNA in diabetic rats was associated with decreases in the expression of
      Runx2, Dlx5 and osterix and an unaltered expression of bone morphogenic protein
      2. The level of RANK protein increased and Runx2 protein decreased in diabetic
      rats. These changes in the bone of STZ-induced diabetic rats were reversed by
      insulin-treatment. These suggested that short-term IDDM induced upregulation of
      osteoclastogenesis with an increase in RANK and downregulation of
      osteoblastogenesis with a decrease in Runx2 in bone.

PMID- 20818504
TI  - SiRNA-mediated PIAS1 silencing promotes inflammatory response and leads to injury
      of cerulein-stimulated pancreatic acinar cells via regulation of the P38MAPK
      signaling pathway.
AB  - Our aim in this study was to investigate the changes of inflammatory response by
      protein inhibitor of activated signal transducer and activator of transcription 1
      (PIAS1) gene silencing treatment in cerulein-stimulated AR42J cells, and relate
      them to changes in cell injury, thus providing evidence for developing clinical
      therapies. This study examined the effects of cerulein on the activity of P38
      mitogen activated protein kinase (P38MAPK), c-jun NH2-terminal kinase/stress
      activated protein kinase and the inflammatory mediators released by PIAS1 gene
      silenced AR42J cells. Consequently, the markers including DNA ladder, cell
      apoptotic rat, cell cycles, levels of cell cycle and apoptotic related factors
      were used to determine the effects of PIAS1 gene silencing on the cerulein
      induced cell injury. The results indicated that in the cerulein-stimulated PIASI
      silencing cells, the activity of P38MAPK was enhanced, while at the same time,
      the levels of inflammatory mediators such as the tumor necrosis factor-alpha,
      interleukin (IL)-1beta, IL-6 and matrix metallopeptidase-9, were markedly higher
      than those of other cerulein-stimulated cells. Thus, the cerulein-stimulated
      PIASI gene-silenced cells obviously increased cell arrest in the G1/M phase by
      increasing P21 and P27 expression, and also induced apoptosis by regulating the
      P53 signaling pathway. This study suggests that the down-regulation of PIAS1 is
      efficacious at enhancing the expression of inflammatory mediators and inducing
      cell injury in acute pancreatitis (AP), thus deteriorating the severity of
      disease. It provides evidence that PIAS1 is a potential therapeutic target for
      AP.

PMID- 20818505
TI  - [Editorial].

PMID- 20818506
TI  - [Small frontal gray matter volume in first-episode depression patients].
AB  - OBJECTIVE: Brain imaging studies have shown that depressed individuals suffer
      from inadequate frontal lobe functions vis a vis smaller frontal lobes. The
      effects of depression's recurrent nature and long-term antidepressant treatment
      are not definitely known. This study aimed to examine frontal lobe volume at the
      onset of clinical depression by including first-episode drug-naive depressed
      patients. METHOD: The study included 23 first-episode drug-free major depression
      patients diagnosed according to the Diagnostic and Statistical Manual of Mental
      Disorders (DSM-IV) and 28 healthy age- and sex-matched controls. Cranial magnetic
      resonance (MR) images were obtained in both groups using a 1.5 Tesla device. Gray
      and white matter volumes in the frontal lobes were measured using the Medical
      Image Processing Analysis and Visualization (MIPAV) computer program. RESULTS:
      Frontal gray matter volume in the patients was lower than that in the control
      group. White matter and total intracranial volume did not differ between the 2
      groups. Small gray matter volume was not correlated with the duration or severity
      of illness. CONCLUSION: The results of this study indicate that frontal lobe gray
      matter volume is low in first-episode depressed patients and is independent of
      both illness severity and duration. This result suggests that the observed
      changes in the frontal lobe could have occurred before the clinical symptoms of
      depression were observed.

PMID- 20818507
TI  - [Undergraduate psychiatric training in Turkey].
AB  - OBJECTIVE: The current trend in medical education is to abandon the experience
      based traditional model and embrace the competency-based education model (CBE).
      The basic principle behind CBE is standardization. The first step in
      standardization is to determine what students must know, what they must
      accomplish, and what attitude they should display, and the establishment of
      educational goals. One of the goals of the Psychiatric Association of Turkey,
      Psychiatric Training Section is to standardize psychiatric training in Turkish
      medical schools. This study aimed to determine the current state of undergraduate
      psychiatric training in Turkish medical schools. METHOD: Questionnaires were sent
      to the psychiatry department chairs of 41 medical schools. Data were analyzed
      using descriptive statistical methods. RESULTS: Of the 41 department chairs that
      were sent the questionnaire, 29 (70%) completed and returned them, of which 16
      (66.7%) reported that they had already defined goals and educational objectives
      for their undergraduate psychiatric training programs. The Core Education
      Program, prepared by the Turkish Medicine and Health Education Council, was
      predominately used at 9 (37.5%) medical schools. Pre-clinical and clinical
      training schedules varied between medical schools. In all, 3 of the medical
      schools did not offer internships in psychiatry. The majority of chairs
      emphasized the importance of mood disorders (49.9%) and anxiety disorders (40%),
      suggesting that these disorders should be treated by general practitioners.
      Computer technology was commonly used for lecturing; however, utilization of
      interactive and skill-based teaching methods was limited. The most commonly used
      evaluation methods were written examination (87.5%) during preclinical training
      and oral examination (91.6%) during clinical training. CONCLUSION: The most
      important finding of this study was the lack of a standardized curriculum for
      psychiatric training in Turkey. Standardization of psychiatric training in
      Turkish medical schools must be developed.

PMID- 20818508
TI  - [The perceived burden of care and its correlates in schizophrenia].
AB  - OBJECTIVE: The present study aimed to investigate the perceived level of burden
      of care and its correlates in family members of schizophrenia patients. METHOD:
      The study included 239 schizophrenic patients that were followed-up at the
      psychiatric outpatient clinics of Izmir Ataturk Education and Research Hospital,
      and Celal Bayar University Medical School, and 239 of their primary caregivers.
      Patients were assessed using the Positive and Negative Syndrome Scale (PANNS),
      Global Assessment of Functioning Scale (GAF), Social Functioning Scale (SFS),
      Brief Cognitive State Examination (BCE), and UKU Side Effect Rating Scale. Their
      primary caregivers were assessed using the Perceived Family Burden Scale (PFBS),
      Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). RESULTS:
      Caregiver PFBS scores ere correlated with male patients, female caregivers,
      inadequate social support, economic difficulty, the presence of chronic physical
      disorder in the caregivers, patient violence toward the caregivers, total
      duration of illness, the number of patient hospitalizations, PANNS total and
      subscale scores, and SFS, BDI, and BAI scores. Perceived burden of care was
      predicted by the severity of the patients' positive symptoms, SFS
      independence/competence and interpersonal functioning subscale scores, and
      caregivers' anxiety and depression levels. CONCLUSION: In order to decrease the
      burden of care in schizophrenia we recommend effective management of patient
      symptoms, enhancement of patient social functioning, interventions that target
      caregivers with high levels anxiety and depression, and social support provided
      by healthcare professionals.

PMID- 20818509
TI  - [Demographic and clinical characteristics in schizophrenia: a multi center cross
      sectional case record study].
AB  - OBJECTIVE: The aim of the present study is to assess the relationship between
      demographic characteristics and suicide attempts, physically aggressive behavior,
      substance abuse, repeated hospitalizations, and continuous illness course .
      METHOD: The medical records of patients from three different treatment centers
      were assessed. The relationship between demographics and clinical characteristics
      were assessed. Logistic regression analysis was conducted to determine the
      predicting factors for suicide attempts, physically aggressive behavior, heavy
      smoking, repeated hospitalizations, and continuous illness course. RESULTS: The
      medical records of a total of 720 patients with schizophrenia were assessed. Of
      these patients, 68% were never married, 56% were unemployed, and 69% were living
      with their parents. 35% of the patients had a relative diagnosed with a psychotic
      disorder. The mean age for the onset of the illness was found to be 23.5, with no
      difference between females and males. 50% of the patients had had repeated
      hospitalizations. The duration of untreated psychosis was 10.8 months and 28% of
      the patients had been through a continuous course of the illness. 57% of the
      patients were found to be regular smokers; 55% of the patients had physically
      aggressive behavior; 52% had experienced a suicidal ideation and attempt; 28% had
      made at least one suicide attempt. The percentage of patients having had a legal
      issue related to their illness was 11%. Heavy smoking was predicted with the
      continuous illness and male gender. Physically aggressive behavior was predicted
      with suicide ideation and attempts, being single, having insufficient family
      support, and having undergone frequent hospitalization. Repeated hospitalizations
      were predicted with suicide attempts and having a legal problems; continuous
      course of illness was predicted with being unemployed and lack of family support;
      suicide attempt was predicted with duration of the illness. CONCLUSION: When both
      sexes were compared, the lack of difference at the onset of disease between the
      two suggests that there might be other factors playing a role in this phenomenon.
      The relationship between suicidal ideation and behavior and physical aggressive
      behavior, indicates that these two might share common underlying mechanisms.
      Possible significant relationships between demographic and clinical
      characteristics should be kept in mind for the prevention, treatment, and
      rehabilitation approaches in dealing with schizophrenia.

PMID- 20818510
TI  - [The validity and reliability of the Turkish version of the anxiety sensitivity
      index-3].
AB  - OBJECTIVE: Anxiety sensitivity has been defined as an excessive fear from senses
      and symptoms of anxiety. The aim of the present study is to investigate the
      validity and reliability of Anxiety Sensitivity Index-3 (ASI-3) and adapting it
      into Turkish. METHOD: The study group consisted of 150 healthy individuals
      without any psychiatric disorder and 300 patients with an anxiety disorder and/or
      major depressive disorder according to DSM-IV criteria. All subjects included in
      the study were evaluated by means of the Mini International Neuropsychiatric
      Interview, ASI-3, Anxiety Sensitivity Index (ASI), State-Trait Anxiety Inventory
      Trait Form (STAI-T), Beck Depression Inventory (BDI) and Somatosensory
      Amplification Scale (SAS). RESULTS: The validity part of the study revealed that
      the scale differentiates the patients from the healthy group in all patient
      subgroups except for anxiety disorder NOS. The scale was found to be highly
      correlated to ASI (r=0.85) and moderately correlated to STAI-T (r=0.68), BDI
      (r=0.57) and SAS (r=0.47). In factor analysis, ASI-3 was found to be composed of
      3 factors: physical, cognitive and social. It was also found that ASI-3 had a
      high internal consistency (Cronbachalpha=0.93) and the scale had a fairly good
      test-retest reliability (r=0.64, p<0.001). CONCLUSION: According to the present
      study, the ASI-3 Turkish version was shown to be a valid and a reliable scale.

PMID- 20818511
TI  - [Professional containment methods used in psychiatry wards: justifications for
      their utilization, types, international practices, and perceptions].
AB  - OBJECTIVE: The aim of this review is to examine the literature on professional
      containment methods, to draw attention to this important topic concerning which
      relevant research remains limited in our country and to offer professionals the
      opportunity to make evaluations utilizing holistic perspectives. METHOD:
      Relevant, obtainable studies published within the last 15 years, but primarily
      after the year 2000, were included in this retrospective literature review. For
      this purpose a literature search was conducted via-internet based search engines,
      including Pubmed, Science Direct, Medline, Psychinfo, the ULAKBIM Turkish
      Medicine Index and the Turkish Psychiatry Index, using the keywords containment
      methods, psychiatry, aggression, conflict, restraint, seclusion and mental health
      hospitals, in different combinations. RESULTS: According to the literature,
      professional containment methods are defined as methods used to prevent harm to
      patients or others as a result of the patient's conflict-provoking behaviour
      (aggression, absconding, rule breaking, refusing medication etc.) in psychiatric
      wards. These methods include the use of mechanical/physical restraint, seclusion,
      compulsory intramuscular sedation, observation, and pro re nata (prn) medication.
      The type and frequency of use, views or attitudes to methods varies between
      different countries. CONCLUSION: Although professional containment methods are an
      effective management strategy, they may cause physical and psychological damage
      to both patient and staff. So the use of these methods in psychiatric care
      settings remains controversial and an ongoing source of legal and ethical
      dilemmas. Despite discussions, the containment methods used in the past remain
      present as a part of psychiatric treatment and care. There is a need for standard
      practice guidelines to ensure the security of patients and staff and to use those
      methods effectively and correctly. In conclusion, it is necessary that health
      care professionals be informed about preparing the new guidelines and using
      professional containment methods effectively.

PMID- 20818512
TI  - [Treatment of vaginismus with EMDR: a report of two cases].
AB  - Vaginismus is a type of sexual dysfunction in which spasm of the vaginal
      musculature prevents penetrative intercourse. The main diagnostic criterion is
      the presence of recurrent or persistent involuntary spasm of the musculature of
      the outer third of the vagina that interferes with sexual intercourse. In many
      cases associated pain or the fear of pain may contribute to its persistence.
      Herein we report 2 patients that presented with vaginismus that developed
      secondary to childhood sexual trauma, which was treated with the Eye Movement
      Desensitization and Reprocessing (EMDR) technique. EMDR is a non-pharmacologic
      treatment for psychological trauma. Randomized controlled trials with
      posttraumatic stress disorder patients and with victims of sexual abuse have
      shown that EMDR is effective. The standard 8-phase EMDR protocol was used in both
      of the presented cases. Following 3 sessions of EMDR, the patients exhibited a
      substantial reduction in self-reported and clinician-rated anxiety, and a
      reduction in the credibility of dysfunctional beliefs concerning sexual
      intercourse. These findings support the notion that EMDR could be an effective
      treatment alternative for patients with vaginismus of traumatic etiology.

PMID- 20818513
TI  - [Asperger syndrome with highly exceptional calendar memory: a case report].
AB  - Some patients with pervasive developmental disorders develop unusual talents,
      which are characterized as savant syndrome. Herein we present neuropsychological
      examination and brain imaging (fMRI and brain SPECT) findings of an 18-year-old
      male with Asperger syndrome and highly unusual calendar memory.
      Neuropsychological evaluation of the case indicated mild attention, memory, and
      problem solving deficits, and severe executive function deficits that included
      conceptualization, category formation, and abstraction. Functional MRI findings
      showed activation above the baseline level (P<0.05) in the bilateral inferior
      parietal lobule, precuneus, superior and middle frontal gyri, and medial frontal
      cortex. Brain SPECT findings, in comparison to rest-SPECT findings, showed that
      there was hypoperfusion in some brain regions, including the right frontal cortex
      and right parietal cortex. Baseline blood perfusion in the left frontal cortex
      was also observed, as well as hypoperfusion in the right parietal-occipital
      cortex and in the right basal ganglion (compared to the left side). The results
      of the present study and further research will contribute to our understanding of
      calendar memory and savant syndrome.

PMID- 20818514
TI  - [Adolescent onset obsessive compulsive disorder presented as dissociative
      disorders: role of drug assisted interview].
AB  - Paediatric Obsessive Compulsive Disorder (OCD) is still under-diagnosed, despite
      significant advances made in identifying obsessive-compulsive symptoms. The
      authors report a case of adolescent-onset OCD presenting as a mixed dissociative
      disorder. The drug assisted interview provided a breakthrough in revising the
      correct diagnosis of the clinical condition. The psychopathology of the patient
      contains sexual and aggressive obsessions without any compulsions. Adolescent OCD
      can present as dissociative disorders and a thiopentone interview can be helpful
      in revealing the distress associated with OCD.

PMID- 20818515
TI  - [Short-term patient acceptance of emergency psychiatry].

PMID- 20818516
TI  - Bioassays and field immersion tests: a comparison of the antifouling activity of
      copper-free poly(methacrylic)-based coatings containing tertiary amines and
      ammonium salt groups.
AB  - This paper focuses on the activity spectrum of three dimethylalkyl tertiary
      amines as potential active molecules and the corresponding ammonium salt-based
      antifouling (AF) paints. Bioassays (using marine bacteria, microalgae and
      barnacles) and field tests were combined to assess the AF activity of coatings.
      Bioassay results demonstrated that the ammonium salt-based paints did not inhibit
      the growth of microorganisms (except the dimethyldodecylammonium-based coatings)
      and that the tertiary amines were potent towards bacteria, diatoms, and barnacle
      larvae at non-toxic concentrations (therapeutic ratio, LC50/EC50, <1). The
      results from field tests indicated that the ammonium salt-based coatings
      inhibited the settlement of macrofouling and the dimethylhexadecylammonium-based
      coatings provided protection against slime in comparison with PVC blank panels.
      Thus, results from laboratory assays did not fully concur with the AF activity of
      the paints in the field trial.

PMID- 20818517
TI  - Quantitative determination of mycotoxins in urine by LC-MS/MS.
AB  - Naturally occurring mycotoxins are responsible for a wide array of adverse health
      effects. The measurement of urinary mycotoxin levels is a useful means of
      assessing an individual's exposure, but the development of sensitive and accurate
      analytical methods for detecting mycotoxins and their metabolites in urine
      samples is challenging. Urinary mycotoxins are present in low pg ml-1
      concentrations, and the chromatographic identification of their metabolites can
      be obscured by other endogenous metabolites. We developed an analytical method
      focused on the selection of two appropriate multiple-reaction monitoring
      transition for unambiguous identification and quantification of carcinogenic
      aflatoxin M1 (AFM1), ochratoxin A (OTA) and fumonisin B1, B2 (FB1, FB2) in urine
      samples from a small volunteer group in a pilot study. AFM1, OTA, FB1 and FB2
      were concentrated selectively, interfering substances were removed using an
      immunoaffinity column (IAC), and mycotoxins were measured using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) in combination with a stable
      isotope standard-dilution assay (SIDA). The method was sensitive enough to
      measure mycotoxins and their metabolites at pg ml-1 levels in urine. The
      combination of LC-MS/MS and SIDA was critical to distinguishing pseudo-OTalpha
      interference from genuine OTalpha. Twelve urine samples contained OTA ranging
      from 0.013 to 0.093 ng ml-1 (mean = 0.031 ng ml-1). AFM1 were detected in one
      sample at a 0.002 ng ml-1 level, while FB1 and FB2 were undetectable in all 12
      samples. None of the samples in this pilot study contained a detectable level of
      OTalpha, despite the presence of OTA, and this may suggest the need for further
      epidemiological investigation of OTA exposure in the Korean population.

PMID- 20818518
TI  - Effect of triazophos, fipronil and their mixture on miRNA expression in adult
      zebrafish.
AB  - MicroRNA (miRNA) plays a crucial role in gene expression regulation. However, no
      data are available on change of miRNA expression of zebrafish (Danio rerio) after
      treatment with pesticides. We evaluated the effect of fipronil (5-amino-1-[2, 6
      dichloro-4-(trifluoromethyl) phenyl]-4-[(trifluoromethyl) sulfinyl]-1H-pyrazole-3
      carbonitrile) and triazophos (3-(O, O-diethyl)-1-phenyl thiophosphoryl-1, 2, 4
      triazol) and their mixture on miRNA expression in zebrafish.MiRNA expression
      profiles in zebrafish were altered after treatment with these chemicals. An
      association between these chemicals and the expression of 21 miRNAs was found 96
      h after treatment. Among them, 14 miRNAs were differentially expressed due to the
      treatments with fipronil, triazophos and their mixture; 5 miRNAs showed altered
      expression level after treatment with formulations of these chemicals; miR-29b
      and miR-738 were differentially expressed after treatment with adjuvants. MiRNAs
      might present a novel toxicological response that could be used as a
      toxicological biomarker and have a different direction for future investigations
      of their association with miRNAs involved in chemical related diseases.

PMID- 20818519
TI  - The health risk assessment of organochlorine pesticides in smoked fish products
      available in Szczecin, Poland.
AB  - The aim of this study was to determine the concentration of organochlorine
      pesticides [HCH and isomers (alpha, beta, gamma), aldrin, dieldrin, endrin,
      heptachlor and heptachlor epoxide and DDT and its metabolites (op'-DDD, pp'-DDD,
      op'-DDT, pp'-DDE, pp'-DDT] in smoked fish. Analysis was made of 12 typical smoked
      fish products that are the most popular among customers from the city of
      Szczecin, Poland. Pesticide residues were found in all samples of smoked fish.
      The smoked sprat and cold-smoked Baltic salmon were the most contaminated smoked
      fish products in terms of chlorine pesticides. The sum of DDT metabolites ranged
      from 1.48 (smoked mackerel) to 35.53 ng/g wet weight (smoked sprat), with the
      lowest concentrations found for op'-DDT and the highest for pp'-DDE. The level of
      heptachlor epoxide isomer B was low and ranged from 0.06 +/- 0.01 (smoked eel) to
      0.27 +/- 0.07 ng/g w.w. (smoked sprat). The content of heptachlor was 0.48-1.99
      ng/g w.w. Concentration of endrin was higher compared to other pesticides, ranged
      from 1.50 (cold-smoked salmon fillet) to 16.84 ng/g w.w (hot-smoked warehou). The
      contamination of smoked products was significantly low and poses no risk to the
      health of consumers provided that they eat a diverse diet. The concentration of
      organochlorine pesticides in the analysed products was below the standards
      accepted in European countries.

PMID- 20818520
TI  - Corynebacterium glutamicum as an indicator for environmental cobalt and silver
      stress--a proteome analysis.
AB  - Cobalt and silver are toxic for cells, but mechanisms of this toxicity are
      largely unknown. Analysis of Corynebacterium glutamicum proteome from cells grown
      in control and cobalt or silver enriched media was performed by two dimensional
      gel electrophoresis (2DE) followed by mass spectrometry. Our results indicate
      that the cell adapted to cobalt stress by inducing five defense mechanisms:
      Scavenging of free radicals, promotion of the generation of energy, reparation of
      DNA, reparation and biogenesis of Fe-S cluster proteins and supporting and
      reparation of cell wall. In response to the detoxification of Ag+ many proteins
      were up-regulated, which involved reparation of damaged DNA, minimizing the toxic
      effect of reactive oxygen species (ROS) and energy generation. Overexpression of
      proteins involved in cell wall biosynthesis (1,4-alpha-glucan branching enzyme
      and nucleoside-diphosphate-sugar epimerase) upon cobalt stress and induction of
      proteins involved in energy metabolism (2-methylcitrate dehydratase and 1, 2
      methylcitrate synthase) upon silver demonstrate the potential of these enzymes as
      biomarkers of sub-lethal Ag+ and Co toxicity.

PMID- 20818521
TI  - Effect of moisture and compost on fate of azoxystrobin in soils.
AB  - The effect of compost-amendment and moisture status on the persistence of
      azoxystrobin [methyl (E)-2-{2-(6-(2-cyanophenoxy) pyrimidin-4-yloxy) phenyl}-3
      methoxyacrylate], a strobilurin fungicide, in two rice-growing soils was studied.
      Azoxystrobin is more sorbed in the silt loam (K f - 4.66) soil than the sandy
      loam (K f - 2.98) soil. Compost-amendment at 5 % levels further enhanced the
      azoxystrobin sorption and the respective Kf values in silt loam and sandy loam
      soils were 8.48 and 7.6. Azoxystrobin was more persistent in the sandy loam soil
      than the silt loam soil. The half-life values of azoxystrobin in nonflooded and
      flooded silt loam soil were 54.7 and 46.3 days, respectively. The corresponding
      half-life values in the sandy loam soils were 64 and 62.7 days, respectively.
      Compost application enhanced persistence of azoxystrobin in the silt loam soil
      under both moisture regimes and half-life values in non-flooded and flooded soils
      were 115.7 and 52.8 days, respectively. However, compost enhanced azoxystrobin
      degradation in the sandy loam soil and half-life values were 59 (nonflooded) and
      54.7 days (flooded). The study indicates that compost amendment enhanced
      azoxystrobin sorption in the soils. Azoxystrobin is more persistent in non
      flooded soils than the flooded soils. Compost applications to soils had mixed
      effect on the azoxystrobin degradation.

PMID- 20818522
TI  - Rapid resolution liquid chromatography-tandem mass spectrometry method for the
      determination of endocrine disrupting chemicals (EDCs), pharmaceuticals and
      personal care products (PPCPs) in wastewater irrigated soils.
AB  - A multiresidue analytical method was developed for the determination of 9
      endocrine disrupting chemicals (EDCs) and 19 pharmaceuticals and personal care
      products (PPCPs) including acidic and neutral pharmaceuticals in water and soil
      samples using rapid resolution liquid chromatography-tandem mass spectrometry
      (RRLC-MS/MS). Solid phase extraction (SPE), and ultrasonic extraction combined
      with silica gel purification were applied as pretreatment methods for water and
      soil samples, respectively. The extracts of the EDCs and PPCPs in water and soil
      samples were then analyzed by RRLC-MS/MS in electrospray ionization (ESI) mode in
      three independent runs. The chromatographic mobile phases consisted of Milli-Q
      water and acetonitrile for EDCs and neutral pharmaceuticals, and Milli-Q water
      containing 0.01 % acetic acid (v/v) and acetonitrile: methanol (1:1, v/v) for
      acidic pharmaceuticals at a flow rate of 0.3 mL/min. Most of the target compounds
      exhibited signal suppression due to matrix effects. Measures taken to reduce
      matrix effects included use of isotope-labeled internal standards, and
      application of matrix-match calibration curves in the RRLC-MS/MS analyses. The
      limits of quantitation ranged between 0.15 and 14.08 ng/L for water samples and
      between 0.06 and 10.64 ng/g for solid samples. The recoveries for the target
      analytes ranged from 62 to 208 % in water samples and 43 to 177 % in solid
      samples, with majority of the target compounds having recoveries ranging between
      70-120 %. Precision, expressed as the relative standard deviation (RSD), was
      obtained less than 7.6 and 20.5 % for repeatability and reproducibility,
      respectively. The established method was successfully applied to the water and
      soil samples from four irrigated plots in Guangzhou. Six compounds namely
      bisphenol-A, 4-nonylphenol, triclosan, triclocarban, salicylic acid and clofibric
      acid were detected in the soils.

PMID- 20818523
TI  - Influence of benomyl and prometryn on the soil microbial activities and community
      structures in pasture grasslands of Slovakia.
AB  - The effects of pesticides (a herbicide and a fungicide) on the microbial
      community structure and their activity were analyzed in soil from four alpine
      pasture grasslands in Slovakia. Specifically, the effects of the herbicide,
      Gesagard (prometryn active ingredient), and fungicide, Fundazol 50 WP (benomyl
      active ingredient), on the microbial respiration activity (CO2 production), the
      numbers of selective microbial physiological groups (CFU.g(-1)) and the structure
      (relative abundance) of soil microbial communities [(phospholipid fatty acid
      (PLFA)] were analyzed under controlled laboratory conditions. All treatments
      including the treatments with pesticides increased (statistically significantly)
      the production of CO2 in all fields during 21 days of incubation and posed a
      statistically insignificant negative influence on the numbers of the observed
      physiological groups of microorganisms. The significantly negative influence was
      evaluated only in the numbers of two physiological groups; spores of bacteria
      utilizing organic nitrogen and bacteria, and their spores utilizing inorganic
      nitrogen. A shift in the microbial composition was evident when the PLFA patterns
      of samples from different sites and treatments were compared by the Principal
      Component Analysis (PCA). According to the second component PCA 2 (15.95 %) the
      locations were grouped into two clusters. The first one involved the Donovaly and
      Dubakovo sites and the second one contained the Velka Fatra and Mala Fatra
      locations. The PLFA composition of the soils showed important changes after the
      treatment with pesticides according to PCA 1 (66.06 %). Other treatments had not
      had a significant effect on the soil microbial community with the exception of
      the population of fungi. The lower relative abundance (significant effect) of
      Gram-positive bacteria, actinomycetes and general group of bacteria were
      determined in samples treated by the herbicide Gesagard. The application of
      fungicide Fundazol decreased (statistically significantly) the relative abundance
      of actinomycetes and general group of bacteria and paradoxically increased the
      population of fungi.

PMID- 20818524
TI  - Intersectionality, critical race theory, and American sporting oppression:
      examining black and gay male athletes.
AB  - This article examines the influence of the racial categories of White and Black
      and the sexual categories of gay and straight on sporting American men. The
      effect of the intersection of these cultural categories is discussed by
      investigating the exclusion of athletes who are both Black and gay, as well as
      highlighting the culturally perceived differences of (straight) Black and (White)
      gay men. However, the analysis accounts for more than just difference, examining
      the commonalities of oppression between these discrete identity groups. We use
      the research on Black athletes to call for further empirical study on gay
      athletes. It is argued that critical race theory and intersectionality offer
      complex and nuanced understandings of these oppressions, which, when theorizing
      is left solely to the realm of poststructuralism, can otherwise be missed.

PMID- 20818525
TI  - Visibility that demystifies: gays, gender, and sex on television.
AB  - A content analysis of 98 episodes of primetime entertainment programs on
      commercial broadcast and cable television stations from the 2005-2006 season
      showed that gay characters on television were more likely to be shown in sexual
      situations than straight characters, and women were more likely to be shown in
      same-sex sexual situations than men. In addition, gay characters were more likely
      to be depicted as sexually active on cable television than they were on
      commercial broadcast television, and they were more likely to be relegated to
      guest star status on commercial broadcast television than on cable television.
      The study also showed that gay characters made up 7.5% of all the characters
      studied. This study discusses the implications of these findings for gay and
      straight audiences.

PMID- 20818526
TI  - Seeking solace in West Hollywood: sexual orientation-based hate crimes in Los
      Angeles County.
AB  - Many thriving "gay communities" across the United States report high levels of
      sexual orientation-based hate crimes every year, raising questions about the
      level of safety in these gay communities and neighborhoods. This study examines
      hate crime data from 2002-2006 in Los Angeles County and the relationship those
      hate crimes have to West Hollywood, the best known gay community of Los Angeles
      County. Results suggest that although West Hollywood does consistently report
      high numbers of hate crimes, this does not reflect a greatly increased risk to
      any one lesbian, gay, or bisexual person. Results suggest that we need to
      consider other variables as predictors (such as poverty, business density, and
      population density) in determining safe versus unsafe space, rather than just the
      percentage of lesbians, gay, and bisexuals in a population.

PMID- 20818528
TI  - Heterosexual men's anger in response to male homosexuality: effects of erotic and
      non-erotic depictions of male-male intimacy and sexual prejudice.
AB  - The present study compared effects of erotic and non-erotic depictions of male
      male intimacy on the experience of anger in heterosexual men. Data came from
      three independent laboratory studies designed to elicit anger in response to
      erotic or non-erotic depictions of male-male and male-female intimacy. All
      participants completed a measure of sexual prejudice and anger was assessed
      before and after viewing the erotic or non-erotic video. Among high-prejudiced
      men, viewing erotic and non-erotic intimate behavior between two men elicited
      significant increases in anger relative to viewing comparable behavior between a
      male-female dyad. In contrast, among low-prejudiced men, viewing erotic, but not
      non-erotic, intimate behavior between two men elicited significant increases in
      anger relative to viewing comparable behavior between a male-female dyad.
      Implications for understanding heterosexual men's anger, and aggression, toward
      gay men were discussed.

PMID- 20818527
TI  - Latino gay and bisexual men's relationships with non-gay-identified men who have
      sex with men.
AB  - This study investigated relationships between Latino gay-identified men in
      metropolitan New York City and their non-gay-identified male partners. Phase 1
      consisted of in-depth interviews (N = 33), and Phase 2 consisted of quantitative
      surveys (N = 120) with Brazilian, Colombian, and Dominican men who have sex with
      men (MSM). A majority of participants reported having had sex with heterosexually
      identified men, and in many cases, the relationship was sustained over time. We
      found mixed results concerning an attitude sometimes attributed to Latinos that
      sexual orientation is defined by sexual role, with receptive MSM seen as gay and
      insertive MSM seen as straight. Although there were no significant associations
      between partner sexual orientation and unprotected anal intercourse, gay men were
      less likely to take the insertive role in oral or anal sex with straight
      identified male partners than with gay partners.

PMID- 20818529
TI  - Religiosity as a Protective Factor against Heavy Episodic Drinking (HED) in
      Heterosexual, Bisexual, Gay, and Lesbian Young Adults.
AB  - Although religiosity has been shown to be associated with positive outcomes in
      studies of general population samples, few studies have considered the potential
      differential effect of religiosity on those who are consolidating gay, lesbian,
      or bisexual (GLB) identities. Logistic regression analyses using a sample of
      13,038 emerging adults from the National Longitudinal Survey of Adolescent Health
      (Add Health) revealed main effects for religiosity and a significant religiosity
      x sexual identity interaction in women. Specifically, religiosity was protective
      against alcohol use and heavy episodic drinking (HED) in heterosexual women, but
      not lesbian women. In bisexual women, higher religiosity increased the odds of
      alcohol use and HED. Among men, religiosity was protective, with no differential
      effects based on sexual identity. Prevention efforts should consider that
      individual religiosity may be a risk, rather than protective factor for some
      young adults.

PMID- 20818530
TI  - Rural men, sexual identity and community.
AB  - The relationship between rurality and men's sexuality remain relatively
      unexplored. This study addresses the knowledge gap in the research literature by
      focusing on men who have sex with men in rural areas across Ontario, Canada.
      Employing a constructivist grounded theory methodology, interviews were conducted
      with 32 men across 28 geographic locales consisting of populations of less than
      10,000 people. Men identified as gay, bisexual, queer/bisexual, or refused
      labels. These self-selected identifiers were then explored to determine how
      participants conceptualized and organized their sexual identities in relation to
      context. Participants held divergent management strategies that resulted in two
      general identity grouping: "natives" and "transplanters."

PMID- 20818534
TI  - Profile of polychlorinated biphenyls in the brown alga Padina sanctae-crucis
      along the Orote dump coastline, Orote Peninsula, Western Guam.
AB  - The purpose of this study was to determine whether the brown seaweed Padina
      sanctae-crucis might be used as a biomonitor organism to determine the location,
      distribution, and type of polychlorinated biphenyls (PCB) present along a
      contaminated tropical coastline. Polychlorinated biphenyls were detected in P.
      sanctae-crucis collected from near-shore waters along a 4-km stretch of
      coastline. The profile of PCB levels from samples obtained at 13 sites along the
      coastline demonstrated a positive concentration gradient as sample locations
      progressed toward the dump site. Sample locations nearest the dump site revealed
      PCB levels twofold higher than background levels for P. sanctae-crucis.
      Chromatograms of samples obtained nearest the dump site indicated a similarity to
      the Aroclor 1260 fingerprint. The P. sanctae-crucis frond trimmings used for
      laboratory analysis were approximately 3-5 wk old. This study was conducted 8 mo
      following the completion of the removal actions at the dump site. Data suggest a
      release of Aroclor 1260 into the marine environment approximately 7 mo following
      the completion of removal actions at the dump site.

PMID- 20818536
TI  - Acute health effects associated with exposure to volcanic air pollution (vog)
      from increased activity at Kilauea Volcano in 2008.
AB  - In 2008, the Kilauea Volcano on the island of Hawai'i increased eruption activity
      and emissions of sulfurous volcanic air pollution called vog. The purpose of this
      study was to promptly assess for a relative increase in cases of medically
      diagnosed acute illnesses in an exposed Hawaiian community. Using a within-clinic
      retrospective cohort design, comparisons were made for visits of acute illnesses
      during the 14 wk prior to the increased volcanic emissions (low exposure) to 14
      wk of high vog exposure when ambient sulfur dioxide was threefold higher and
      averaged 75 parts per billion volume per day. Logistic regression analysis
      estimated effect measures between the low- and high-exposure cohorts for age,
      gender, race, and smoking status. There were statistically significant positive
      associations between high vog exposure and visits for medically diagnosed cough,
      headache, acute pharyngitis, and acute airway problems. More than a sixfold
      increase in odds was estimated for visits with acute airway problems, primarily
      experienced by young Pacific Islanders. These findings suggest that the elevated
      volcanic emissions in 2008 were associated with increased morbidity of acute
      illnesses in age and racial subgroups of the general Hawaiian population.
      Continued investigation is crucial to fully assess the health impact of this
      natural source of sulfurous air pollution. Culturally appropriate primary- and
      secondary-level health prevention initiatives are recommended for populations in
      Hawai'i and volcanically active areas worldwide.

PMID- 20818538
TI  - In vitro dermal penetration of 4-chloro-3-methylphenol from commercial metal
      working fluid and aqueous vehicles.
AB  - The biocide 4-chloro-3-methylphenol (CMP, CAS number 59-50-7) is a common
      additive to metal-working fluids (MWF) and building materials. National Institute
      for Occupational Safety and Health (NIOSH) researchers previously identified and
      quantified CMP in a commercial water-soluble MWF, TRIM VX, and demonstrated
      irritancy and sensitization potential of both TRIM VX and CMP alone after dermal
      exposure in a murine model. In the current study, the in vitro human epidermal
      permeability of CMP contained in a working dilution of TRIM VX (20% in water) was
      evaluated and, for comparison, permeability from an aqueous buffer was also
      assessed. CMP penetration was also measured from transient exposures to 20% TRIM
      VX. To address differences in penetration rates from 20% TRIM VX and from buffer,
      the role of thermodynamic activity of CMP in the 2 vehicles on dermal penetration
      was investigated. Static headspace gas chromatography was used to measure vapor
      pressures and infer fractional thermodynamic activities of CMP in the mixtures.
      Permeability coefficient (k(p)) of CMP from 20% TRIM VX was (4.1 +/- 0.8) x 10(
      3) cm/h (mean +/- SD, n = 5), and CMP was found at a concentration of 3555 +/-
      191 microg/ml in this donor. In contrast, k(p) was 0.18 +/- 0.03 cm/h (n = 5) at
      a similar concentration (3919 +/- 240) from buffer donor. Steady-state fluxes
      from 20% TRIM VX and buffer were comparable when expressed as functions of
      thermodynamic activity of CMP in the donor, rather than as concentrations.
      Transient (20 or 40 min) exposures of epidermal membranes to 20% TRIM VX (n = 4)
      resulted in total penetration of 4.2 +/- 1.2 and 7.3 +/- 0.8 microg/cm(2),
      respectively; these amounts are comparable to amounts predicted using a simple
      algebraic equation.

PMID- 20818535
TI  - Effects of titanium dioxide nanoparticle exposure on neuroimmune responses in rat
      airways.
AB  - Exposure to ambient nanoparticles (defined as particulate matter [PM] having one
      dimension <100 nm) is associated with increased risk of childhood and adult
      asthma. Nanomaterials feature a smaller aerodynamic diameter and a higher surface
      area per unit mass ratio compared to fine or coarse-sized particles, resulting in
      greater lung deposition efficiency and an increased potential for biological
      interaction. The neurotrophins nerve growth factor and brain-derived neurotrophic
      factor are key regulatory elements of neuronal development and responsiveness of
      airway sensory neurons. Changes in their expression are associated with
      bronchoconstriction, airway hyperresponsiveness, and airway inflammation. The
      neurogenic-mediated control of airway responses is a key pathophysiological
      mechanism of childhood asthma. However, the effects of nanoparticle exposure on
      neurotrophin-driven airway responses and their potential role as a predisposing
      factor for developing asthma have not been clearly elucidated. In this study, in
      vivo inhalation exposure to titanium dioxide nanoparticles (12 mg/m(3); 5.6 h/d
      for 3 d) produced upregulation of lung neurotrophins in weanling (2-wk-old) and
      newborn (2-d-old) rats but not in adult (12-wk-old) animals compared to controls.
      This effect was associated with increased airway responsiveness and upregulation
      of growth-related oncogene/keratine-derived chemokine (GRO/KC; CXCL1, rat
      equivalent of human interleukin [IL]-8) in bronchoalveolar lavage fluid. These
      data show for the first time that exposure to nanoparticulate upregulates the
      expression of lung neurotrophins in an age-dependent fashion and that this effect
      is associated with airway hyperresponsiveness and inflammation. These results
      suggest the presence of a critical window of vulnerability in earlier stages of
      lung development, which may lead to a higher risk of developing asthma.

PMID- 20818539
TI  - The role of the mediodorsal thalamic nucleus in human olfaction.
AB  - Olfaction has a unique dual-route pathway to the neocortex - one being via the
      mediodorsal nucleus of the thalamus (MDNT). In this study we explored the role of
      the MDNT pathway, by comparing six patients with MDNT lesions, with 14 controls,
      on tests of general olfactory ability (i.e., odor acuity, discrimination, naming,
      recognition memory and hedonic judgement), visual control and neuropsychological
      tests, and tests of olfactory attention. The MDNT patients performed normally on
      most general olfactory tests but showed varying impairments on tests of olfactory
      attention. These findings suggest that the MDNT pathway is involved, either
      specifically or generically, in mediating human olfactory attention.

PMID- 20818537
TI  - Rhinitis associated with pesticide use among private pesticide applicators in the
      agricultural health study.
AB  - Farmers commonly experience rhinitis but the risk factors are not well
      characterized. The aim of this study was to analyze cross-sectional data on
      rhinitis in the past year and pesticide use from 21,958 Iowa and North Carolina
      farmers in the Agricultural Health Study, enrolled 1993-1997, to evaluate
      pesticide predictors of rhinitis. Polytomous and logistic regression models were
      used to assess association between pesticide use and rhinitis while controlling
      for demographics and farm-related exposures. Sixty-seven percent of farmers
      reported current rhinitis and 39% reported 3 or more rhinitis episodes. The
      herbicides glyphosate [odds ratio (OR) = 1.09, 95% confidence interval (95% CI) =
      1.05-1.13] and petroleum oil (OR = 1.12, 95% CI = 1.05-1.19) were associated with
      current rhinitis and increased rhinitis episodes. Of the insecticides, four
      organophosphates (chlorpyrifos, diazinon, dichlorvos, and malathion), carbaryl,
      and use of permethrin on animals were predictors of current rhinitis. Diazinon
      was significant in the overall polytomous model and was associated with an
      elevated OR of 13+ rhinitis episodes (13+ episodes OR = 1.23, 95% CI = 1.09
      1.38). The fungicide captan was also a significant predictor of rhinitis. Use of
      petroleum oil, use of malathion, use of permethrin, and use of the herbicide
      metolachlor were significant in exposure-response polytomous models. Specific
      pesticides may contribute to rhinitis in farmers; agricultural activities did not
      explain these findings.

PMID- 20818540
TI  - Abnormal visual phenomena in posterior cortical atrophy.
AB  - Individuals with posterior cortical atrophy (PCA) report a host of unusual and
      poorly explained visual disturbances. This preliminary report describes a single
      patient (CRO), and documents and investigates abnormally prolonged colour
      afterimages (concurrent and prolonged perception of colours complimentary to the
      colour of an observed stimulus), perceived motion of static stimuli, and better
      reading of small than large letters. We also evaluate CRO's visual and vestibular
      functions in an effort to understand the origin of her experience of room tilt
      illusion, a disturbing phenomenon not previously observed in individuals with
      cortical degenerative disease. These visual symptoms are set in the context of a
      4-year longitudinal neuropsychological and neuroimaging investigation of CRO's
      visual and other cognitive skills. We hypothesise that prolonged colour after
      images are attributable to relative sparing of V1 inhibitory interneurons;
      perceived motion of static stimuli reflects weak magnocellular function; better
      reading of small than large letters indicates a reduced effective field of
      vision; and room tilt illusion effects are caused by disordered integration of
      visual and vestibular information. This study contributes to the growing
      characterisation of PCA whose atypical early visual symptoms are often
      heterogeneous and frequently under-recognised.

PMID- 20818541
TI  - Conscious and unconscious processing of fear after right amygdala damage: a
      single case ERP-study.
AB  - In this study, we describe a 58-year-old male patient (FZ) with a right-amygdala
      lesion after temporal lobe infarction. FZ is unable to recognize fearful facial
      expressions. Instead, he consistently misinterprets expressions of fear for
      expressions of surprise. Employing EEG/ERP measures, we investigated whether
      presentation of fearful and surprised facial expressions would lead to different
      response patterns. We also measured ERPs to aversively conditioned and
      unconditioned fearful faces. We compared ERPs elicited by supraliminally and
      subliminally presented conditioned fearful faces (CS+), unconditioned fearful
      faces (CS-) and surprised faces. Despite FZ's inability to recognize fearful
      facial expressions in emotion recognition tasks, ERP components showed different
      response patterns to pictures of surprised and fearful facial expressions,
      indicating that covert or implicit recognition of fear is still intact.
      Differences between ERPs to CS+ and CS- were only found when these stimuli were
      presented subliminally. This indicates that intact right amygdala function is not
      necessary for aversive conditioning. Previous studies have stressed the
      importance of the right amygdala for discriminating facial emotional expressions
      and for classical conditioning. Our study suggests that the right amygdala is
      necessary for explicit recognition of fear, while implicit recognition of fear
      and classical conditioning may still occur following lesion of the right
      amygdala.

PMID- 20818542
TI  - Dynamic-intentional thalamic aphasia: a failure of lexical-semantic self
      activation.
AB  - BACKGROUND: Previous research has described patients with aphasia from thalamic
      lesions, some of whom were non-fluent with intact comprehension, others who were
      fluent with impaired comprehension, and some of whom are non-fluent with impaired
      comprehension. Whereas these three subtypes usually have normal repetition, they
      had impaired naming, suggesting a deficit in lexical (phonological word forms)
      semantic processing. We report a patient with a left thalamic hemorrhage in which
      lexical-semantic representations appear to be intact but the patient demonstrates
      an inability to spontaneously activate his lexical-semantic system. METHODS: A 82
      year-old, right-handed man presented with decreased verbal fluency and memory
      loss following a thalamic hemorrhage. Neuropsychological assessment revealed
      significant decrements in verbal fluency with intact naming, comprehension,
      repetition and vocabulary. CONCLUSIONS: To the best of our knowledge this pattern
      of language disturbance, which mirrors dynamic aphasia induced by frontal
      lesions, has not previously been described with thalamic injury. The thalamus has
      strong connections with the frontal lobe and rather than degradation of lexical
      semantic representations, this patient's thalamic lesion probably induced frontal
      lobe dysfunction with a failure to spontaneously active lexical semantic
      representations.

PMID- 20818543
TI  - To the barricades!

PMID- 20818544
TI  - Deidentification and its discontents: response to the Open Peer Commentaries.

PMID- 20818545
TI  - Is deidentification sufficient to protect health privacy in research?

PMID- 20818546
TI  - The intellectual and moral integrity of bioethics: response to commentaries on "A
      case study in unethical transgressive bioethics: 'Letter of concern from
      bioethicists' about the prenatal administration of dexamethasone".

PMID- 20818547
TI  - Privacy overkill.

PMID- 20818548
TI  - "Human non-subjects research": privacy and compliance.

PMID- 20818549
TI  - Urge overkill: protecting deidentified human subjects at what price?

PMID- 20818550
TI  - Electronic health records and research: privacy versus scientific priorities.

PMID- 20818551
TI  - Managing patient expectations about deidentification.

PMID- 20818552
TI  - Racial, ethnic, and tribal classifications in biomedical research with biological
      and group harm.

PMID- 20818553
TI  - Group compromise: perfect cases make problematic generalizations.

PMID- 20818554
TI  - Guiding deidentification forward.

PMID- 20818555
TI  - Why deidentification fails research subjects and researchers.

PMID- 20818556
TI  - Data identifiability and privacy.

PMID- 20818557
TI  - More than one binary.

PMID- 20818558
TI  - Gift giving to biobanks.

PMID- 20818560
TI  - Still concerned.

PMID- 20818559
TI  - A case study in unethical transgressive bioethics: "Letter of concern from
      bioethicists" about the prenatal administration of dexamethasone.
AB  - On February 3, 2010, a "Letter of Concern from Bioethicists," organized by
      fetaldex.org, was sent to report suspected violations of the ethics of human
      subjects research in the off-label use of dexamethasone during pregnancy by Dr.
      Maria New. Copies of this letter were submitted to the FDA Office of Pediatric
      Therapeutics, the Department of Health and Human Services (DHHS) Office for Human
      Research Protections, and three universities where Dr. New has held or holds
      appointments. We provide a critical appraisal of the Letter of Concern and show
      that it makes false claims, misrepresents scientific publications and websites,
      fails to meet standards of evidence-based reasoning, makes undocumented claims,
      treats as settled matters what are, instead, ongoing controversies, offers "mere
      opinion" as a substitute for argument, and makes contradictory claims. The Letter
      of Concern is a case study in unethical transgressive bioethics. We call on
      fetaldex.org to withdraw the letter and for co-signatories to withdraw their
      approval of it.

PMID- 20818561
TI  - Description and defense of prenatal diagnosis and treatment with low-dose
      dexamethasone for congenital adrenal hyperplasia.

PMID- 20818562
TI  - Speaking of accuracy.

PMID- 20818563
TI  - Quo OHRP?: faithful arbiter or pro wrestling ref?

PMID- 20818564
TI  - On cultural sanctions for shaping our children's genitalia.

PMID- 20818565
TI  - Why history matters: fetal dex and intersex.

PMID- 20818566
TI  - The view from the inside: more confusion (and coziness) than consent.

PMID- 20818567
TI  - Why I signed, and why I would do it again.

PMID- 20818568
TI  - An attempt to shut down discourse about a controversial practice will not benefit
      patients, human subjects, the bioethics community, or the research community.

PMID- 20818569
TI  - Attracting attention: right or wrong.

PMID- 20818570
TI  - Politics and persuasion in medical controversies.

PMID- 20818571
TI  - Influence of fouling on the efficiency of sacrificial anodes in providing
      cathodic protection in Southeast Asian tropical seawater.
AB  - Aluminum and zinc based sacrificial anodes are routinely used to provide
      corrosion protection to metals (typically steel) exposed to seawater, for example
      in steel pipelines and storage tanks. However, the high fouling rates experienced
      in South East Asia means that both the anodes and the metals to be protected
      rapidly become coated with macrofoulers, which could potentially prevent the
      anodes from being effective. The present study, involving exposure tests of up to
      18 months, indicates that both aluminum and zinc sacrificial anodes remain
      effective even after being completely coated with biofouling. Furthermore, it was
      easier to remove the biofouling on the cathodically protected samples than on
      their unprotected counterparts, possibly due to the higher local pH produced by
      cathodic protection at the metal and seawater interface.

PMID- 20818572
TI  - A computational method for developing hierarchical large deformation viscoelastic
      models of the contracting heart.
AB  - In this study, a new computational method for modelling the contracting heart is
      described. Using this method, the cardiac wall is constructed from basic,
      repeating contractile units that represent individual myocardial units and
      collagen, each with its own set of parameters, including orientation, passive and
      active behaviour and stimulation propagation. The method allows individual
      control of each structural unit (e.g. at the level of a single myocardial unit).
      Feasibility of modelling dynamic heart contraction using this method is
      demonstrated using 2D cross-sections and simplified 3D geometries. Effects of non
      contractile scar and myopathic tissue were also tested in these geometrical
      configurations. Results from the 2D and 3D simulations were, overall, in
      agreement with well-established physiological data. The present method holds
      promise for modelling complex heart pathologies, abnormal mechanical properties
      (e.g. myocardial infarcts) and electrical conduction properties (branch blocks),
      and their spatial distributions across the myocardial tissues.

PMID- 20818573
TI  - The portrayal of depression in the three most popular English-language Black
      American magazines in the USA: Ebony, Essence, and Jet.
AB  - OBJECTIVE?: To examine how depression is portrayed within a specific racialized
      group. DESIGN: Manifest and latent content analysis of the three highest
      circulating magazines directed toward Black-American readers, Essence, Ebony, and
      Jet, from 2000 to 2007. RESULTS: The findings demonstrate ambiguity and
      contradictions about depression's meaning and incidence, as well as the
      availability, accessibility, and suitability of medical treatment. All of these
      are linked to racialized identities among Black Americans. CONCLUSION: Magazine
      portrayal of depression in these magazines can only be understood in the context
      of experienced racism, oppression, and ethnic identity among Blacks.

PMID- 20818574
TI  - Identity, peer relationships, and adolescent girls' sexual behavior: an
      exploration of the contemporary double standard.
AB  - The idea of a sexual double standard emphasizes that men have more sexual
      freedom, whereas women are subject to social sanctions for the same behaviors.
      This research uses a sample of adolescent women to examine the social
      consequences of reporting a greater number of sex partners. The research explores
      whether there are broader social costs and feelings of low self-worth associated
      with a high number of sex partners, and also focuses on characteristics of the
      adolescents' close friends. The analyses of quantitative data (n = 600) provide
      support for the emphasis on the adolescents' immediate network of friends:
      Friends' attitudes and behaviors were significant predictors of respondents' own
      sexual experiences, while those reporting a higher number of sex partners did not
      report a lack of popularity, desire for more friends, or lower self-esteem. In
      depth relationship history narratives collected from a subset of respondents (n =
      46) provide additional context. Women often recognized the existence of a double
      standard on a societal or school level, but support or acceptance provided by the
      more immediate network of similarly situated friends serves as a buffer against
      such negative attributions. The findings suggest that programs targeting sexual
      behaviors should focus on how peer norms influence girls' sexual choices.

PMID- 20818575
TI  - Children dating childhood memories.
AB  - How accurate are children when dating very long-term memories? Chinese and
      European Canadian 8-, 11-, and 14-year-olds (N=344) recalled and dated memories
      from before they went to school in a memory fluency task. Parents provided
      verification of children's memories and age estimates. Across all age and culture
      groups, a telescoping effect (i.e., events were dated as taking place more
      recently than they actually did) was found for earlier memories (before 48
      months) and a reverse telescoping effect for later memories (after 48 months).
      Older children showed a greater tendency to telescope earlier memories and a
      weaker tendency to reverse telescope later memories than did younger children.
      Euro-Canadian children showed larger reverse telescoping than Chinese children.
      These are the first systematic findings concerning the accuracy of children's
      dating of very long-term memories. They shed new light on the phenomenon of
      telescoping and have implications for research on childhood amnesia.

PMID- 20818576
TI  - Atypical conduction aphasia and the right hemisphere: Cross-hemispheric
      plasticity of phonology in a developmentally dyslexic and dysgraphic patient with
      early left frontal damage.
AB  - We report the rare case of a patient, JNR, with history of mixed handedness,
      developmental dyslexia, dysgraphia, and attentional deficits associated with a
      Klippel-Trenaunay syndrome and a small subcortical frontal lesion involving the
      left arcuate fasciculus. In adulthood, he suffered a large right perisylvian
      stroke and developed atypical conduction aphasia with deficits in input and
      output phonological processing and poor auditory-verbal short-term memory.
      Lexical-semantic processing for single words was intact, but he was unable to
      access meaning in sentence comprehension and repetition. Reading and writing
      deficits worsened after the stroke and he presented a combination of
      developmental and acquired dysgraphia and dyslexia with mixed lexical and
      phonological processing deficits. This case suggest that a small lesion sustained
      prenatally or early in life could induce a selective rightward shift of phonology
      sparing the standard left hemisphere lateralisation of lexical-semantic
      functions.

PMID- 20818577
TI  - Indirect versus direct feedback in computer-based Prism Adaptation Therapy.
AB  - Prism Adaptation Therapy (PAT) is an intervention method in the treatment of the
      attention disorder neglect (Frassinetti, Angeli, Meneghello, Avanzi, & Ladavas,
      2002; Rossetti et al., 1998). The aim of this study was to investigate whether
      one session of PAT using a computer-attached touchscreen would produce similar
      after-effects to the conventional box normally used in PAT. In four experiments,
      81 healthy subjects and 7 brain-injured patients diagnosed with neglect were
      subjected to a single session of PAT under two conditions: (1) using the original
      box, and (2) using a computer-based implementation of PAT. The session of PAT
      included a pre-exposure step involving pointing at 30 targets without feedback;
      an exposure step involving pointing at 90 targets with prism goggles and
      feedback; and a post-exposure step involving pointing at 60 targets, with no
      goggles and no feedback. The results indicate that the expected similarity in the
      after-effect produced by the two conditions seems to occur only if subjects
      receive feedback on pointing precision by seeing their fingertip during the
      exposure step. Attempts to provide feedback indirectly via icons on the computer
      screen failed to produce the expected size in the after-effect. The findings have
      direct implications for computer-based treatment of visuospatial disorders in the
      future and computer-assisted rehabilitation in general.

PMID- 20818578
TI  - Toxicity of organic pollutants to seven aquatic organisms: effect of polarity and
      ionization.
AB  - The toxicity of organic chemicals to Vibrio fischeri, river bacteria, algae,
      Daphnia magna and fishes were analysed. The results showed that the toxicity of
      chemicals to narcotics was dependent on hydrophobicity. A single model for both
      polar and non-polar narcotics was developed by inclusion of a polarity descriptor
      as well as the hydrophobic parameter. The highly hydrophobic polar narcotics
      could be treated as non-polar narcotics because their polar functional group(s)
      make(s) a relatively small contribution to polarity as compared with their
      hydrophobicity. In order to investigate the toxic mechanism of action for
      reactive compounds, the response-surface approach was used to develop models
      derived from easily calculated descriptors. The stepwise analysis selected the
      octanol/water partition coefficient and a polarity descriptor to parameterize bio
      uptake and reactivity, respectively, for seven species. Benzoic acids can be
      easily absorbed into the unicellular bacteria, but this is not the case for
      multicellular D. magna and fish. Their toxicity to V. fischeri is much higher
      than that to D. magna and carp. Regression analysis was performed based on the
      model that we developed for ionizable compounds. Good correlations were observed
      by introducing the correction factor for ionizable compounds. The toxic
      mechanisms are discussed.

PMID- 20818579
TI  - Development of an ecotoxicity QSAR model for the KAshinhou Tool for Ecotoxicity
      (KATE) system, March 2009 version.
AB  - The KAshinhou Tool for Ecotoxicity (KATE) system, including ecotoxicity
      quantitative structure-activity relationship (QSAR) models, was developed by the
      Japanese National Institute for Environmental Studies (NIES) using the database
      of aquatic toxicity results gathered by the Japanese Ministry of the Environment
      and the US EPA fathead minnow database. In this system chemicals can be entered
      according to their one-dimensional structures and classified by substructure. The
      QSAR equations for predicting the toxicity of a chemical compound assume a linear
      correlation between its log P value and its aquatic toxicity. KATE uses a
      structural domain called C-judgement, defined by the substructures of specified
      functional groups in the QSAR models. Internal validation by the leave-one-out
      method confirms that the QSAR equations, with r(2 )> 0.7, RMSE <or= 0.5, and n >
      5, give acceptable q(2) values. Such external validation indicates that a group
      of chemicals with an in-domain of KATE C-judgements exhibits a lower root mean
      square error (RMSE). These findings demonstrate that the KATE system has the
      potential to enable chemicals to be categorised as potential hazards.

PMID- 20818580
TI  - Domain of EPI suite biotransformation models.
AB  - Knowledge of the interpolative region or applicability domain (AD) of structure
      activity relationships is believed to improve predictive accuracy. The present
      work was undertaken to characterize the AD of EPI Suite biotransformation models
      and evaluate the performance of selected AD assessment methods. AD methods were
      applied to the training sets of four models representing different end-points,
      and the predictive accuracy was then evaluated using six independent validation
      sets. Two of the models estimated a continuous variable (log half-life) from
      fragment descriptors. For biotransformation in fish (BCFBAF) and hydrocarbon
      biodegradation (BioHCwin), the approach using ranges, with preprocessing by
      analysis of principal components, worked reasonably well in identifying subsets
      of validation chemicals that have higher root mean squared error than for all
      validation chemicals. AD methods were also applied to two classification models,
      Biowin3 (which predicts the time required to achieve complete aerobic
      biodegradation) and Biowin5 (the probability of ready biodegradation in the OECD
      301C test). Structure-based AD methods (fingerprints, atom environments) showed
      some success, but descriptor-based AD methods were not useful in identifying
      misclassified chemicals. For Biowin3 the largest percentage of misclassified
      chemicals was obtained for chemicals for which prediction was based on molecular
      weight alone, which suggests the need to revise the fragment library of the
      model.

PMID- 20818581
TI  - Pharmacophore-based virtual screening and docking studies on Hsp90 inhibitors.
AB  - Hsp90 (Heat shock protein 90) is an important therapeutic target for the
      treatment of cancer. To identify important chemical features for Hsp90 inhibitory
      activity, a 3D-QSAR pharmacophore model was developed using a set of 61
      inhibitors (a training set of 31 and a test set of 30 compounds) belonging to a
      series of 2-amino-6-halopurine and 7'-substituted benzothiazolothio- and
      pyridinothiazolothio-purines. The best HypoGen model consisted of five
      pharmacophoric features: one hydrogen bond acceptor (HBA), one hydrogen bond
      donor (HBD) and three hydrophobic (HY) groups. It showed a high correlation
      coefficient (r = 0.943) and low root mean square deviation (RMSD = 0.751). This
      model was validated against 30 known Hsp90 inhibitors, where it showed a high
      predictive value for R(2)pred = 0.805], thus confirming that HY, HBA and HBD
      features are essential for Hsp90 inhibition. The validated pharmacophore model
      (Hypo-1) was used as a 3D query for virtual screening to retrieve potential
      inhibitors from the Maybridge and National Cancer Institute (NCI) databases. The
      hit compounds were subsequently subjected to molecular docking studies and,
      finally, five hits were prioritized as potential leads based on GoldScore
      function.

PMID- 20818583
TI  - Role of physicochemical properties in the estimation of skin permeability: in
      vitro data assessment by Partial Least-Squares Regression.
AB  - Skin provides passage for the delivery of drugs. The in vitro and in vivo testing
      of chemicals for estimation of dermal absorption is very time consuming, costly
      and has many ethical difficulties related to human and animal testing. The
      solution to the problem is Quantitative structure-permeability relationships.
      This method relates dermal penetration properties of a range of chemical
      compounds to their physicochemical parameters. In the present study, an effort
      has been made to develop models for the accurate prediction of skin permeability
      using a large, diverse dataset through the combination of various regression
      methods coupled with the Genetic Algorithm (GA)/Interval Partial Least-Squares
      Algorithm (iPLS). The descriptors were calculated using e-DRAGON and ADME Pharma
      Algorithms-Abrahams descriptors. The original dataset was divided into a training
      set and a testing set using the Kennard-Stone Algorithm. The selection of
      descriptors was made by the GA and iPLS. The model applicability domain was
      determined. The results showed that a three-parameter model built through Partial
      Least-squares Regression was most accurate with r(2) of 0.936.

PMID- 20818582
TI  - Mammary carcinogen-protein binding potentials: novel and biologically relevant
      structure-activity relationship model descriptors.
AB  - Previously, SAR models for carcinogenesis used descriptors that are essentially
      chemical descriptors. Herein we report the development of models with the cat-SAR
      expert system using biological descriptors (i.e., ligand-receptor interactions)
      rat mammary carcinogens. These new descriptors are derived from the virtual
      screening for ligand-receptor interactions of carcinogens, non-carcinogens, and
      mammary carcinogens to a set of 5494 target proteins. Leave-one-out validations
      of the ligand mammary carcinogen-non-carcinogen model had a concordance between
      experimental and predicted results of 71%, and the mammary carcinogen-non-mammary
      carcinogen model was 72% concordant. The development of a hybrid fragment-ligand
      model improved the concordances to 85 and 83%, respectively. In a separate
      external validation exercise, hybrid fragment-ligand models had concordances of
      81 and 76%. Analyses of example rat mammary carcinogens including the food
      mutagen and oestrogenic compound PhIP, the herbicide atrazine, and the drug
      indomethacin; the ligand model identified a number of proteins associated with
      each compound that had previously been referenced in Medline in conjunction with
      the test chemical and separately with association to breast cancer. This new
      modelling approach can enhance model predictivity and help bridge the gap between
      chemical structure and carcinogenic activity by descriptors that are related to
      biological targets.

PMID- 20818584
TI  - Screening for low aquatic bioaccumulation. 1. Lipinski's 'Rule of 5' and
      molecular size.
AB  - Aquatic bioconcentration factors are critical in PBT assessment of industrial
      chemicals under REACH. Reliable indicators based on physico-chemical properties
      and molecular attributes of chemicals with low bioconcentration potential have
      been searched to de-prioritize non-accumulative chemicals in order to avoid
      unnecessary biotests that do not produce risk-relevant information. Developed to
      screen drug candidates, Lipinski's 'Rule of 5' identifies chemicals with poor
      oral absorption based on criteria in partitioning, molecular weight and hydrogen
      bonding. This parameter ensemble has been supplemented with molecular diameter
      and tested for its adequacy to filter chemicals with low bioconcentration
      potential. Perhaps (not) surprisingly, the application of the 'Rule of 5' fails
      to protectively identify non-accumulative compounds because other processes
      dominate the uptake in aquatic environments as compared with oral absorption. No
      robust evidence was found for cut-offs in bioconcentration related to molecular
      size. However, pragmatic thresholds in molecular weight (>650 g mol(-1)) and
      lipophilicity (log K(OW) < 3 or > 10) have been verified to securely de
      prioritize 30-40% of chemicals of low concern with regard to the B criterion.

PMID- 20818585
TI  - Comparison of prediction methods for the uptake of As, Cd and Pb in carrot and
      lettuce.
AB  - The New Model Framework (NMF) for uptake into crops is based on particle
      deposition and Transfer factors from soil to plant calculated from the BAse de
      donnees sur les teneurs en Elements Traces metalliques de Plantes Potageres
      (BAPPET) database. Besides NMF, approaches developed by the National Institute of
      Public Health and the Environment (RIVM), Hough, and the United States
      Environmental Protection Agency (US EPA), and the Contaminated Land Exposure
      Assessment (CLEA) approach were tested. Experimental data were assembled from the
      BAPPET database and Danish background data of As, Cd and Pb in soil, air and
      crops was collected. None of the models proved able to estimate the measured
      concentrations in plants from the BAPPET database with an absolute normalized
      error smaller than 70%. On average, the predictions had an error of 80-250%.
      However, when applying the models to the rural Danish background scenario, the
      NMF and other models predicted the concentrations in carrot and lettuce within
      the range of measured values. Regressions considering soil pH, organic matter and
      clay content were not superior to simple transfer factors. The transfer from air
      to plant is significant, at least under background conditions, and should be
      considered in the prediction methods.

PMID- 20818586
TI  - 3D-QSAR studies on triclosan derivatives as Plasmodium falciparum enoyl acyl
      carrier reductase inhibitors.
AB  - 3D-QSAR studies were carried out on a training set of 53 structurally highly
      diverse analogues of triclosan to investigate the correlation of the structural
      properties of triclosan derivatives with the inhibition of the activity of enoyl
      acyl carrier protein reductase in Plasmodium falciparum (PfENR) by employing
      Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity
      Indices Analysis (CoMSIA). The crystal structure bound conformation of triclosan,
      was used as a template for aligning molecules. The probable binding mode
      conformations of other inhibitors were explored according to molecular docking
      and molecular mechanics poisson-boltzmann surface area (MM/PBSA) solvation free
      energy estimation methods using grid based linear Poisson-Boltzmann calculations.
      Predictive 3D-QSAR models, established using routine database alignment rule
      based on crystallographic-bound conformation of template molecule, produced
      statistically significant results with cross-validated r2 cv values of 0.64 and
      0.54 and non-cross-validated r2 ncv values of 0.96 and 0.97 for CoMFA and CoMSIA
      models, respectively. The statistically significant models were validated by a
      test set of nine compounds with predictive r(2) values of 0.534 and 0.765 for
      CoMFA and CoMSIA respectively. Our QSAR model is able to successfully explain the
      geometric and electrostatic complementarities between ligands and receptor and
      provides useful guidelines to design novel triclosan derivatives as Plasmodium
      falciparum enoyl acyl carrier reductase inhibitors.

PMID- 20818587
TI  - Theory of docking scores and its application to a customizable scoring function.
AB  - In general, the docking scoring tends to have a size dependence related to the
      ranking of compounds. In this paper, we describe a novel method of parameter
      optimization for docking scores which reduce the size dependence and can
      efficiently discriminate active compounds from chemical databases. This method is
      based on a simplified theoretical model of docking scores which enables us to
      utilize large amounts of data of known active and inactive compounds for a
      particular target without requiring large computational resources or a
      complicated procedure. This method is useful for making scoring functions for the
      identification of novel scaffolds using the knowledge of active compounds for a
      particular target or a customized scoring function for an interesting family of
      drug targets.

PMID- 20818588
TI  - Using support vector regression coupled with the genetic algorithm for predicting
      acute toxicity to the fathead minnow.
AB  - The potential toxicity of chemicals may present adverse effects to the
      environment and human health. The quantitative structure-activity relationship
      (QSAR) provides a useful method for hazard assessment. In this study, we
      constructed a QSAR model based on a highly heterogeneous data set of 571
      compounds from the US Environmental Protection Agency, for predicting acute
      toxicity to the fathead minnow (Pimephales promelas). An approach coupling
      support vector regression (SVR) with the genetic algorithm (GA) was developed to
      build the model. The generated QSAR model showed excellent data fitting and
      prediction abilities: the squared correlation coefficients (r(2)) for the
      training set and the test set were 0.826 and 0.802, respectively. Only eight
      critical descriptors, most of which are closely related to the toxicity
      mechanism, were chosen by GA-SVR, making the derived model readily interpretable.
      In summary, the successful case reported here highlights that our GA-SVR approach
      can be used as a general machine learning method for toxicity prediction.

PMID- 20818589
TI  - A new graphical representation of similarity/dissimilarity studies of protein
      sequences.
AB  - Based on chaos game representation, a two-dimensional-graphical representation of
      protein sequences is described in which 20 amino acids are rearranged in a cyclic
      order using a PAM250 substitution matrix. A numerical characterisation has been
      developed as a descriptor to compare protein sequences. Finally, an example is
      given in which the dehydrogenase subunit 5 (ND5) protein sequences of nine
      species are compared.

PMID- 20818590
TI  - The role of tribal experiences in shaping Native American health.
AB  - The relatively poor health and healthcare of Native Americans is well documented.
      However, the existing research does not adequately consider unique tribal
      experiences in shaping Native American health. Consequently, the purpose of this
      paper is to assess the role of tribes in explaining measures of healthcare and
      the perceptions of health-related problems. Employing interview data from 219
      members of the Omaha Tribe and Santee Sioux Nation in rural Nebraska, it is found
      that significant tribal distinctions exist in terms of health status, health
      access, and the perceptions of community issues related to health and healthcare.
      These differences are linked with the unique experiences of the tribes as a way
      to illustrate the need for researchers and policy makers to consider the role
      tribes play in shaping health.

PMID- 20818591
TI  - The effects of eliminating supplemental security income drug addiction and
      alcoholism eligibility on the mental health of low-income substance abusers.
AB  - On January 1, 1997, as the result of federal legislation, many low-income
      substance abusers lost income and healthcare benefits provided by the
      Supplemental Security Income (SSI) program. This study examined the effects of
      eliminating drug addiction and alcoholism (DAA) as qualifying impairments for SSI
      benefits on the mental health and mental health treatment utilization of former
      beneficiaries 3.5 years following the policy change. Study participants in four
      Northern California counties were categorized into three comparison groups based
      on their primary income source over the lifetime of the study. Findings indicated
      that overall the reported mental health status of former SSI DAA beneficiaries
      improved following the policy change; however, study participants who relied
      primarily on some other type of public assistance post-termination reported an
      increase in mental health treatment utilization.

PMID- 20818592
TI  - Nonmarital births and state abortion policies.
AB  - This study examines the impact of various restrictive abortion laws on nonmarital
      childbearing since the passage of the 1996 welfare reform bill. The empirical
      results find that the price of an abortion, a Medicaid funding restriction, and a
      waiting period law are associated with a decrease in a state's nonmarital
      birthrate. The negative effects of restrictive abortion laws on a state's
      nonmarital birthrate are found to occur in various age groups. These findings are
      consistent with the hypothesis that restrictive abortion laws induce unmarried
      women to change their level of unprotected sexual activity or contraceptive
      behavior, thereby reducing the likelihood of an unwanted nonmarital pregnancy.

PMID- 20818593
TI  - Long-term and chronic homelessness in homeless women and women with children.
AB  - The Chronic Homelessness initiative has directed millions of federal dollars to
      services for single "unaccompanied homeless" individuals, specifically excluding
      women living with their children. Using a data set with a nationally
      representative sample of homeless adults, we calculated the prevalence rates and
      profiles of long-term homelessness in homeless women (n = 849). With the
      exception of the criterion of being a single "unaccompanied individual," many
      women, including women with children, met the criteria for chronic homelessness
      including having a disability of mental health or substance abuse problems. Our
      findings suggest that the federal definition of chronic homelessness needs to be
      revised.

PMID- 20818594
TI  - Using patient evaluations to empirically assess medicaid programs for social
      justice.
AB  - The Medicaid program serves a social justice function in the United States. The
      program's effectiveness in achieving this aim is traditionally evaluated in terms
      of resource allocation and distribution using measures and concepts such as
      financing, access, and enrollment. The patient's perspective in ascertaining the
      quality of actual care delivery has not been utilized to ascertain social
      justice. This paper uses the confidential evaluations of 40% of the hospitals in
      Rhode Island, New Jersey, and Connecticut to compare the experiences of Medicaid
      patients versus privately insured patients hospitalized in 2002 and cross
      validates results in independent samples collected in 2003 and 2004. The results
      found that Medicaid patients experienced interactions with physicians that
      resulted in lower ratings of statistical and practical significance than
      privately insured patients. Admissions and discharge processes were also rated
      lower by Medicaid patients. The "hotel" amenities provided by hospitals-room and
      meals-were rated more favorably by Medicaid patients. Yet there were no
      significant differences in Medicaid and private insurance patients' overall
      satisfaction with their acute care experience. Medicaid patients' evaluations
      should be considered a key component of evaluating whether a state's Medicaid
      program has achieved patients' and society's need for social justice.

PMID- 20818595
TI  - Osteoporosis: prevention and implications for social work practice and policy.
AB  - Osteoporosis is one of the major disorders of our time and is increasing at an
      alarming rate. It affects over 10 million women in the United States and is
      expected to affect 14 million by the year 2020. There are a number of risk
      factors for osteoporosis that are of a modifiable nature; however, many women do
      not take the necessary precautions to prevent the disease. The reasons that women
      do not actively engage in preventative and remedial strategies to deal with the
      potential for osteoporosis are complex. It is clear that women must have adequate
      knowledge to make informed decisions regarding osteoprotective behaviors. Social
      workers are in a unique position to provide interventions not only on a micro
      level (educating individual clients) but also on a macro level in terms of large
      scale education campaigns focusing on nutrition and exercise both in children and
      in adults. This article examines the reasons for the failure of women to engage
      in osteoprotective behaviors by exploring barriers to prevention and their impact
      on social work policy, practice, and research.

PMID- 20818596
TI  - Mode of delivery and outcomes in very low-birth-weight infants in the vertex
      presentation.
AB  - We sought to determine the relationship between mode of delivery and neonatal
      outcomes in infants <1500 g in a vertex presentation. This was a retrospective
      cohort study of singleton, vertex-presenting infants weighing <1500 g in a level
      III neonatal intensive care unit between July 1993 and July 2006. Infants were
      divided into vaginal or cesarean delivery, and outcomes were compared with
      univariable and multivariable analysis. Of the 937 infants that met inclusion
      criteria, 402 (42.9%) underwent cesarean delivery. After controlling for
      potential confounding variables, there was no increased odds of death (odds ratio
      [OR] = 1.6: 95% confidence interval [CI] 0.8 to 3.0), severe intraventricular
      hemorrhage (IVH; OR = 1.2: 95% CI 0.7 to 1.2), necrotizing enterocolitis (OR =
      0.82: 95% CI 0.35 to 1.9), or sepsis (OR = 0.79: 95% CI 0.44 to 13) in the
      vaginally delivered group compared with the cesarean group. In a post hoc
      analysis, this study had 80% power to detect an absolute difference in death or
      severe IVH of 6% between study groups, with an alpha of 0.05. In our population
      of very low-birth-weight infants, there was no association between mode of
      delivery and neonatal outcomes.

PMID- 20818597
TI  - Pellet culture model for human primary osteoblasts.
AB  - In vitro monolayer culture of human primary osteoblasts (hOBs) often shows
      unsatisfactory results for extracellular matrix deposition, maturation and
      calcification. Nevertheless, monolayer culture is still the method of choice for
      in vitro differentiation of primary osteoblasts. We believe that the delay in
      mature ECM production by the monolayer cultured osteoblasts is determined by
      their state of cell maturation. A functional relationship between the inhibition
      of osteoblast proliferation and the induction of genes associated with matrix
      maturation was suggested within a monolayer culture model for rat calvarial
      osteoblasts. We hypothesize, that a pellet culture model could be utilized to
      decrease initial proliferation and increase the transformation of osteoblasts
      into a more mature phenotype. We performed pellet cultures using hOBs and
      compared their differentiation potential to 2D monolayer cultures. Using the
      pellet culture model, we were able to generate a population of cuboidal shaped
      central osteoblastic cells. Increased proliferation, as seen during low-density
      monolayer culture, was absent in pellet cultures and monolayers seeded at 40,000
      cells/cm2. Moreover, the expression pattern of phenotypic markers Runx2, osterix,
      osteocalcin, col I and E11 mRNA was significantly different depending on whether
      the cells were cultured in low density monolayer, high density monolayer or
      pellet culture. We conclude that the transformation of the osteoblast phenotype
      in vitro to a more mature stage can be achieved more rapidly in 3D culture.
      Moreover, that dense monolayer leads to the formation of more mature osteoblasts
      than low-density seeded monolayer, while hOB cells in pellets seem to have
      transformed even further along the osteoblast phenotype.

PMID- 20818598
TI  - The relationship between energy status and AMP-activated protein kinase in human
      H460 lung cancer cells.
AB  - In cultured cells, glucose and serum provide constant sources of energy and
      growth factors, both of which are important for cell survival and proliferation.
      AMP-activated protein kinase (AMPK) plays a key role in sensing intracellular ATP
      levels and acts as a critical regulator of energy homeostasis. To investigate the
      relationship between energy status and AMPK activity in lung cancer, H460 cells
      were starved in either glucose-free or serum-free medium and then re-stimulated
      with glucose and serum, respectively. The levels of ATP and lactate and the
      activities of AMPK and lactate dehydrogenase (LDH) were analyzed at different
      time intervals. During glucose treatment, the activity of AMPK was induced by
      glucose and showed biphasic reaction kinetics. The ATP level was gradually
      increased up to 2-fold compared with that in serum treatment after 24 h and
      lactate level was decreased to approximately 60%. The LDH activity slightly
      increased and reached a peak after 6 h. During serum treatment, the activity of
      AMPK was suppressed and the ATP level showed a dramatic 30% increase after 1 h.
      In contrast, the lactate level was gradually increased and then reverted to the
      background level after 24 h. The activity of LDH was slightly decreased after 12
      h and eventually returned to the background level. This study showed the
      alteration of energy status in lung cancer cells in response to altered levels of
      glucose and serum. We suggest that the activation of AMPK and inhibition of
      glycolysis might be exploited as therapeutic tactics in cancer treatment.

PMID- 20818599
TI  - Prevalence of anxiety in patients awaiting diagnostic procedures in an oncology
      center in Brazil.
AB  - OBJECTIVE: Anxiety disorders have been shown to undermine the quality of life of
      cancer patients. Unfortunately, medical professionals often neglect to screen for
      anxiety in their patients. The aim of the present study was to describe the
      prevalence of anxiety in patients awaiting diagnostic procedures in an oncology
      center waiting room, and to investigate possible relationships between anxiety
      and demographic and clinical variables. METHODS: A cross-sectional study was
      performed with 398 patients who completed a self-administered questionnaire
      containing the Hospital Anxiety and Depression Scale (HADS) and the State-Trait
      Anxiety Inventory (STAI). RESULTS: Results of the HADS indicated that 38% of
      participants had anxiety, while data from the STAI showed that 46% had either
      high state or trait anxiety. The most frequently cited source of anxiety was
      concern over test results. Age, gender, employment status, and education level
      were correlated with anxiety. CONCLUSIONS: The prevalence of anxiety is high
      among patients awaiting diagnostic procedures. Patients in the waiting room
      should be routinely screened for anxiety. Careful assessment and treatment of
      anxiety are important components in the care of patients with cancer.

PMID- 20818600
TI  - Facilitating reproductive choices: the impact of health services on the
      experiences of young women with breast cancer.
AB  - OBJECTIVE: Chemotherapy and hormone treatments carry significant implications on
      the fertility of young women with breast cancer. Increasingly, nulliparous women
      experience fertility dilemmas due to rising survival rates and pregnancy delay.
      This qualitative study investigated women's responses to being told that
      treatments affected their fertility and how their interactions with health
      services impacted on their experiences. METHODS: Twenty-four women under 40 years
      participated in three focus groups using a flexible interview structure. Data
      were analysed using content analysis and participants subsequently member checked
      the themes generated. RESULTS: The priority for most women was survival, although
      women without children were more willing to take risks. Many women felt that
      pregnancy after breast cancer and methods of egg harvesting carried a significant
      risk to survival and fears appeared to be increased by conflicting advice from
      health professionals. Overall, the women felt the cancer, its treatment options
      and the health service itself had each robbed them of choice. Hence, with
      hindsight, many said they would have welcomed an open and honest discussion with
      a fertility expert to maximise their options. CONCLUSIONS: Young women with
      breast cancer face complex decisions regarding their fertility and treatment
      options. Survival remains the priority for the majority of women. Although there
      is a paucity of evidence concerning many fertility issues, it is essential that
      available options and any potential risks are discussed in a coherent, objective
      fashion. Early referral to specialist fertility services that provide clear,
      cohesive advice can aid informed decision making.

PMID- 20818601
TI  - Geometrically centered region: a "wet" model of protein binding hot spots not
      excluding water molecules.
AB  - A protein interface can be as "wet" as a protein surface in terms of the number
      of immobilized water molecules. This important water information has not been
      explicitly taken by computational methods to model and identify protein binding
      hot spots, overlooking the water role in forming interface hydrogen bonds and in
      filing cavities. Hot spot residues are usually clustered at the core of the
      protein binding interfaces. However, traditional machine learning methods often
      identify the hot spot residues individually, breaking the cooperativity of the
      energetic contribution. Our idea in this work is to explore the role of
      immobilized water and meanwhile to capture two essential properties of hot spots:
      the compactness in contact and the far distance from bulk solvent. Our model is
      named geometrically centered region (GCR). The detection of GCRs is based on
      novel tripartite graphs, and atom burial levels which are a concept more
      intuitive than SASA. Applying to a data set containing 355 mutations, we achieved
      an F measure of 0.6414 when DeltaDeltaG >= 1.0 kcal/mol was used to define hot
      spots. This performance is better than Robetta, a benchmark method in the field.
      We found that all but only one of the GCRs contain water to a certain degree, and
      most of the outstanding hot spot residues have water-mediated contacts. If the
      water is excluded, the burial level values are poorly related to the DeltaDeltaG,
      and the model loses its performance remarkably. We also presented a definition
      for the O-ring of a GCR as the set of immediate neighbors of the residues in the
      GCR. Comparative analysis between the O-rings and GCRs reveals that the newly
      defined O-ring is indeed energetically less important than the GCR hot spot,
      confirming a long-standing hypothesis.

PMID- 20818602
TI  - The expression of stem cell-related indicators as a prognostic factor in human
      lung adenocarcinoma.
AB  - INTRODUCTION: The purpose of the present study was to detect the presence of BASC
      like stem cell-related indicators, such as clara cell secretory protein (CCSP),
      Octamer-4 (OCT4) and Bmi-1, and evaluate their implications in the prognosis of
      patients with lung adenocarcinoma. METHODS: Specimens of 134 cases of lung
      adenocarcinoma were collected after radical surgery from January 1999 to June
      2004. RESULTS: One hundred and twenty-six cases showed cells that were positive
      for CCSP, 99 cases positive for OCT4, 91 cases simultaneous expression of CCSP
      and OCT4 and 74 cases positive for Bmi-1. Bmi-1 was significantly higher in
      patients at stage III compared to patients at stages I and II. The pattern of
      survival curves showed that Bmi-1 was a significant prognostic factor of poor
      overall survival in lung adenocarcinoma patients (P = 0.0000), and the patients
      with OCT4(+) expression showed a greater increase in mortality than OCT4(-)
      patients (P = 0.0103). The results of univariate and multivariate Cox analysis
      revealed that the pathological stages of tumor node metastases (P = 0.037), OCT4
      (P = 0.046) and Bmi-1 expression (P = 0.001) were independent prognostic factors.
      CONCLUSIONS: OCT4 and Bmi-1 may be good biomarkers to predict the prognosis of
      patients with completely resected lung adenocarcinoma.

PMID- 20818603
TI  - Tardive dyskinesia and other movement disorders secondary to aripiprazole.
AB  - The objective of this report is to draw attention to tardive dyskinesia (TD)
      caused by aripiprazole, a third generation antipsychotic. TD has been
      traditionally attributed to typical (first-generation) antipsychotics, but other
      dopamine receptor blocking drugs and atypical (second- and third-generation)
      neuroleptics are emerging as an important cause of TD. We reviewed the medical
      records of patients with TD seen at the Baylor College of Medicine Movement
      Disorders Clinic between 2002 and 2010 to identify patients with TD associated
      with aripiprazole. Among 236 patients with TD seen over the specified period, 8
      (3.4%) were found to have aripiprazole-associated TD. In 5 patients, TD occurred
      after exclusive exposure to aripiprazole. The mean age at onset was 55.8 +/- 14.8
      years with a female predominance. The average duration of treatment with
      aripiprazole was 18.4 +/- 26.4 months. Oro-bucco-lingual stereotypy was seen in
      all patients. In most patients, TD did not spontaneously improve after stopping
      aripiprazole. Of the 5 patients treated with tetrabenazine, 4 improved during
      follow-up. Although aripiprazole, a third generation antipsychotic, has been
      promoted to have a low risk of TD, the drug accounts for about 3.5% of patients
      with TD evaluated in a movement disorders clinic. This largest reported series
      draws attention to the growing incidence of TD and other drug-induced movement
      disorders associated with "atypical antipsychotics."

PMID- 20818604
TI  - Estimation of skeletal muscle energy metabolism in Machado-Joseph disease using
      (31)P-MR spectroscopy.
AB  - The aim of this study was to determine if muscle energy metabolism, as measured
      by (31)P-magnetic resonance spectroscopy (MRS), is a metabolic marker for the
      efficacy of treatment of Machado-Joseph disease (MJD). We obtained (31)P-MRS in
      the calf muscle of 8 male patients with MJD and 11 healthy men before, during,
      and after a 4 minute plantar flexion exercise in a supine position. The data
      showed that there was a significant difference between the groups in terms of the
      PCr/(Pi + PCr) ratio at rest (P = 0.03) and the maximum rate of mitochondrial ATP
      production (V(max)) (P < 0.01). In addition, V(max) was inversely correlated with
      the scale for the assessment and rating of ataxia score (r = -0.34, P = 0.04).
      The MJD group also showed a reduction in V(max) over the course of 2 years (P <
      0.05). These data suggest that this noninvasive measurement of muscle energy
      metabolism may represent a surrogate marker for MJD.

PMID- 20818605
TI  - Nonlinear dynamic analysis of oscillatory repetitive movements in Parkinson's
      disease and essential tremor.
AB  - Uncertainty exists on whether Parkinson's disease (PD) and essential tremor (ET)
      patients have similar degree of impairment during motor tasks. We investigated
      this problem by analyzing nonlinear dynamics of repetitive movements in 21
      control subjects, 33 mild-moderate PD patients, and 18 ET patients. Accelerometer
      signals were recorded during finger tapping and unbounded forearm movements
      between two points, and processed with moving average filtering to generate a new
      signal consisting of the temporal distance between consecutive cycles. We
      calculated: mean interpeak interval (slowness), interpeak interval variability
      (irregularity), and beat decay (BD) of the auto mutual information (AMI) value,
      which estimates signal predictability by measuring the loss of signal information
      over a timescale. Both PD and ET had longer interpeak interval (except for finger
      tapping), higher interpeak interval variability, and higher BD-AMI values than
      controls (P <= 0.007, all comparisons). ET patients had higher BD-AMI values than
      PD (P = 0.003). BD-AMI was the parameter that discriminated better between
      subjects (diagnosis accuracies about 80%). No differences existed between PD
      patients with and without tremor or between PD or ET patients with different
      disease stages, for any parameter. Evaluation of nonlinear dynamics of
      oscillatory repetitive movements is a feasible and promising tool for studying
      movement physiology. Movement performance is more predictable in PD and ET than
      in controls, even in early disease stages. Slowness and irregularity of movement
      in PD and ET cannot be fully explained by tremor. Some common pathogenic
      mechanisms leading to bradykinesia may contribute to this impairment.

PMID- 20818606
TI  - Electrophysiological evaluation of thalamic DBS for orthostatic tremor.

PMID- 20818607
TI  - How well do caregivers detect mild cognitive change in Parkinson's disease?
AB  - Using the Cambridge Behavior Inventory-Revised, this study evaluated the
      relationship between caregiver ratings of cognitive change and neuropsychological
      performance. In sixty-one nondemented patients with Parkinson's Disease (PD; mean
      age = 64.5 years, MMSE = 28.7), 62% met criteria for mild cognitive impairment.
      This group were rated as having more overall change as well as memory and
      behavior change. Caregiver ratings were related to poorer psychomotor speed,
      learning/memory, language, and executive functioning. The capacity for caregivers
      to rate mild cognitive change in PD may be useful to assist in early screening
      and intervention approaches.

PMID- 20818608
TI  - Clinical and biochemical characterization of patients with early infantile onset
      of autosomal recessive GTP cyclohydrolase I deficiency without
      hyperphenylalaninemia.
AB  - Autosomal recessive guanosine triphosphate cyclohydrolase (GTPCH) type I
      deficiency is characterized by complex neurological dysfunction. Patients are
      usually diagnosed with hyperphenylalaninemia in newborn screening. We describe
      two unrelated patients without hyperphenylalaninemia who presented during early
      infancy with severe motor retardation, hypokinesia, and truncal hypotonia. CSF
      homovanillic acid and 5-hydroxyindoleacetic acid as well as tetrahydrobiopterin
      and neopterin were decreased. Diagnosis of recessive GTPCH deficiency was
      confirmed biochemically, and a novel homozygous mutation was identified in one
      patient and a compound-heterozygous mutation of GCH1 in the other. Treatment with
      Levodopa/Carbidopa resulted in striking clinical improvement, with age
      appropriate development at follow-up at 6 years. Autosomal recessive GTPCH
      deficiency should be considered in infants with severe truncal hypotonia even if
      hyperphenylalaninemia or classical extrapyramidal symptoms are missing.
      Neurotransmitter analysis followed by enzyme or mutation analysis can confirm the
      diagnosis, and Levodopa treatment should be started at high-doses.

PMID- 20818609
TI  - Spinocerebellar ataxia type 10: Frequency of epilepsy in a large sample of
      Brazilian patients.
AB  - Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder caused
      by an ATTCT repeat intronic expansion in the SCA10 gene. SCA 10 has been reported
      in Mexican, Brazilian, Argentinean and Venezuelan families. Its phenotype is
      overall characterized by cerebellar ataxia and epilepsy. Interestingly, Brazilian
      patients reported so far showed pure cerebellar ataxia, without epilepsy. Here,
      authors provide a systematic analysis of the presence, frequency and
      electroencephalographic presentation of epilepsy among 80 SCA10 patients from 10
      Brazilian families. Overall, the frequency of epilepsy was considered rare, been
      found in 3.75 % of the cases while this finding in populations from other
      geographic areas reaches 60% of SCA10 cases.

PMID- 20818610
TI  - LRRK2 G2019S mutations are associated with an increased cancer risk in Parkinson
      disease.
AB  - Leucine rich repeat kinase (LRRK2) G2019S mutations are presumed to cause PD
      through a toxic gain of function of the protein kinase. Small molecule kinase
      inhibitors have been developed for the treatment of certain cancers, and some
      antioncogenic agents such as sunitinib, may nonspecifically inhibit LRRK2. Few
      studies, however, have assessed cancer risk in LRRK2 mutation carriers. To
      explore this risk, we evaluated records of Ashkenazi Jewish (AJ) PD patients
      participating in genetic research. Charts were reviewed for 163 unrelated AJ PD
      patients, 31 of whom harbored the G2019S mutation. History of cancer was queried
      at baseline intake using a form reviewing medical conditions, and charts were
      reviewed for all follow-up visits. 9/31 LRRK2 G2019S mutation carriers had
      nonskin cancers, whereas 15/132 without mutations had nonskin cancers,
      representing an almost threefold increased risk in this group (HR 2.9, 95% CI 1.3
      6.6). Age at first nonskin cancer was younger in the LRRK2 carriers (56.0 years)
      than the noncarriers (62.0 years), but was not significant. 67% of the LRRK2
      carriers had their cancer before the onset of PD, whereas only 40% of noncarriers
      developed their first nonskin cancer before onset of PD. While further evaluation
      is warranted, our findings indicate an increased risk of nonskin cancers in LRRK2
      G2019S mutation carriers, which may be related to toxic gain of function of
      mutated LRRK2.

PMID- 20818611
TI  - Dramatic response of facial stereotype/tic to tetrabenazine in the first reported
      cases of neuroferritinopathy in the United States.

PMID- 20818612
TI  - Genetic models of serotonin (5-HT) depletion: what do they tell us about the
      developmental role of 5-HT?
AB  - A large number of hyposerotonergic genetic models have been generated over the
      past few years. Serotonin (5-HT) depletion has been obtained via targeting of
      genes involved in 5-HT synthesis (Tph1 and Tph2), specification and determination
      of the 5-HT phenotype during development (GATA3, Pet1, and Lmx1b), and 5-HT
      storage or clearance (Vmat2 and SERT). Here we review these various models from a
      developmental perspective, beginning with a description of the sources of 5-HT
      during development. We then summarize the neurological and behavioral alterations
      that have been observed in the genetic hyposerotonergic models. Although these
      models appear to have normal brain development and do not exhibit any gross
      morphological defects, problems in somatic growth and physiological functions
      have been observed. Abnormal adult behavior is also seen, although whether it
      results from depletion of 5-HT during development or functional 5-HT deficiencies
      in adult life remains unclear. Evidence from these hyposerotonergic models
      suggests that the developing brain may not need 5-HT for the establishment of
      general organization and structure. However, central 5-HT appears to be necessary
      for postnatal body growth, maturation of respiratory and vegetative control, and
      possibly for the development of normal adult behavior.

PMID- 20818614
TI  - Individual sarcomere lengths in whole muscle fibers and optimal fiber length
      computation.
AB  - Estimation of muscle fiber optimum length is typically accomplished using either
      laser diffraction or by counting the number of sarcomeres in a portion of the
      muscle fiber, measuring the distance that encompasses those sarcomeres and
      dividing by the number of sarcomeres to obtain an average sarcomere length. If
      the sarcomeres are not uniformly distributed, either of these techniques could
      produce errors when estimating optimum lengths. The purposes of this study were:
      to describe new software that automatically analyzes digital images of skeletal
      muscle fibers to measure individual sarcomere lengths; and to use this software
      to measure individual sarcomere lengths along complete muscle fibers to examine
      the influence of computing whole muscle fiber properties from portions of the
      fiber. Six complete muscle fibers were imaged using a digital camera attached to
      a microscope. The images were then processed to achieve the best resolution
      possible, individual sarcomeres along the image were detected, and each
      individual sarcomere length was measured. The software accuracy was compared with
      that of manual measurement and was found to be as accurate. In addition, the time
      to measure individual sarcomere lengths was greatly reduced using the software
      compared with manual measurement. The arrangement of individual sarcomere lengths
      demonstrated long-range correlations, which indicates problems in assuming only a
      portion of a fiber can be used to determine whole fiber properties. This study
      has provided evidence on the number of sarcomeres which must be analyzed to infer
      the properties of whole muscles.

PMID- 20818613
TI  - Ontogeny of the kidney and renal developmental markers in the rhesus monkey
      (Macaca mulatta).
AB  - Nonhuman primates share many developmental similarities with humans, thus they
      provide an important preclinical model for understanding the ontogeny of
      biomarkers of kidney development and assessing new cell-based therapies to treat
      human disease. To identify morphological and developmental changes in protein and
      RNA expression patterns during nephrogenesis, immunohistochemistry and
      quantitative real-time PCR were used to assess temporal and spatial expression of
      WT1, Pax2, Nestin, Synaptopodin, alpha-smooth muscle actin (alpha-SMA), CD31,
      vascular endothelial growth factor (VEGF), and Gremlin. Pax2 was expressed in the
      condensed mesenchyme surrounding the ureteric bud and in the early renal vesicle.
      WT1 and Nestin were diffusely expressed in the metanephric mesenchyme, and
      expression increased as the Pax2-positive condensed mesenchyme differentiated.
      The inner cleft of the tail of the S-shaped body contained the podocyte
      progenitors (visceral epithelium) that were shown to express Pax2, Nestin, and
      WT1 in the early second trimester. With maturation of the kidney, Pax2 expression
      diminished in these structures, but was retained in cells of the parietal
      epithelium, and as WT1 expression was upregulated. Mature podocytes expressing
      WT1, Nestin, and Synaptopodin were observed from the mid-third trimester through
      adulthood. The developing glomerulus was positive for alpha-SMA (vascular smooth
      muscle) and Gremlin (mesangial cells), CD31 (glomerular endothelium), and VEGF
      (endothelium), and showed loss of expression of these markers as glomerular
      maturation was completed. These data form the basis for understanding
      nephrogenesis in the rhesus monkey and will be useful in translational studies
      that focus on embryonic stem and other progenitor cell populations for renal
      tissue engineering and repair.

PMID- 20818615
TI  - Immunohistochemical localization of cytokeratins in the junctional region of
      ectoderm and endoderm.
AB  - Although tridermic species have two junctional regions of ectoderm and endoderm
      between their epidermis and digestive tract, we actually know little about these
      particular boundaries. Cytokeratins are the major intermediate filaments of
      epithelial cells and show a high degree of tissue specificity. Therefore, to
      characterize the epithelial cells in the junctional region of ectoderm and
      endoderm, we immunohistochemically examined the localization of cytokeratins 5,
      7/17, 14, 18, Sox17, and alpha-fetoprotein (AFP) in the oropharyngeal and
      anorectal regions during the mouse gastrulation process. At embryonic day (E)
      9.5, cytokeratins 5, 7/17, 14, and 18 were detected in all epithelial cells of
      the oropharyngeal region. At E12.5, cytokeratin 5-positive cells were not
      observed in the middle area of the oral cavity; however, the immunoreactivity was
      strong in the anterior and posterior areas. The immunoreaction of cytokeratins 18
      was seen only in the middle and posterior areas of the oral mucosa. Cytokeratins
      7/17 and 14 were localized in all areas of the oropharyngeal region. Sox17 and
      AFP, which are endodermal markers, were detected in the middle and posterior
      areas of the oral mucosa, but not in the anterior area. Moreover, this same
      localization pattern of cytokeratins also existed in the anorectal region of the
      E12.5 embryo, suggesting that the localization of cytokeratins and endodermal
      markers might give an implication for the boundary between ectoderm and endoderm.
      These results also suggest that these cytokeratins are useful molecules for
      monitoring the epithelial cell differentiation in the junctional region of the
      germ layers.

PMID- 20818616
TI  - Reprogramming directional cell motility by tuning micropattern features and
      cellular signals.

PMID- 20818617
TI  - Three-dimensional printing of interconnects by laser direct-write of silver
      nanopastes.

PMID- 20818618
TI  - Remotely triggerable drug delivery systems.
AB  - Triggerable drug delivery systems enable on-demand controlled release profiles
      that may enhance therapeutic effectiveness and reduce systemic toxicity.
      Recently, a number of new materials have been developed that exhibit sensitivity
      to visible light, near-infrared (NIR) light, ultrasound, or magnetic fields. This
      responsiveness can be triggered remotely to provide flexible control of dose
      magnitude and timing. Here we review triggerable materials that range in scale
      from nano to macro, and are activated by a range of stimuli.

PMID- 20818619
TI  - The role of surface functionality on acute cytotoxicity, ROS generation and DNA
      damage by cationic gold nanoparticles.

PMID- 20818620
TI  - Oil microsealing: a robust micro-compartmentalization method for on-chip chemical
      and biological assays.
AB  - A simple and robust method to compartmentalize aqueous solutions into an array of
      independent microchambers is presented. The array of microchambers fabricated in
      poly(dimethylsiloxane) are filled with the sample solution through a microfluidic
      channel and then sealed with oil to isolate the microchambers from each other. A
      water reservoir close to the microchambers allows the maintainance and incubation
      of sub-nanoliter solutions (e.g., at 37  degrees C) within the chambers for hours
      without any problem of evaporation. Once assembled, the device is self
      sustainable and can be used for different application purposes. As a
      demonstration, the device configuration is shown to be suitable for
      spatiotemporal control of the inner solution conditions by light stimulation
      through a photomask. This method was applied for the generation of regular EmGFP
      (emerald green fluorescent protein) expression arrays, selective photobleaching,
      photopatterning of calcium concentration, and cell culture in independent
      microchambers.

PMID- 20818621
TI  - Intracellular nanoparticle coating stability determines nanoparticle diagnostics
      efficacy and cell functionality.
AB  - Iron oxide nanoparticles (NPs) are frequently employed in biomedical research as
      magnetic resonance (MR) contrast agents where high intracellular levels are
      required to clearly depict signal alterations. To date, the toxicity and
      applicability of these particles have not been completely unraveled. Here, we
      show that endosomal localization of different iron oxide particles results in
      their degradation and in reduced MR contrast, the rate of which is governed
      mainly by the stability of the coating. The release of ferric iron generates
      reactive species, which greatly affect cell functionality. Lipid-coated NPs
      display the highest stability and furthermore exhibit intracellular clustering,
      which significantly enhances their MR properties and intracellular persistence.
      These findings are of considerable importance because, depending on the nature of
      the coating, particles can be rapidly degraded, thus completely annihilating
      their MR contrast to levels not detectable when compared to controls and greatly
      impeding cell functionality, thereby hindering their application in functional in
      vivo studies.

PMID- 20818622
TI  - Hierarchically ordered structures enabled by controlled evaporative self
      assembly.

PMID- 20818623
TI  - Polyhydroxy fullerenes for non-invasive cancer imaging and therapy.

PMID- 20818624
TI  - Ordering and printing virus arrays: a straightforward way to functionalize
      surfaces.

PMID- 20818625
TI  - Integration of a close-packed quantum dot monolayer with a photonic-crystal
      cavity via interfacial self-assembly and transfer.

PMID- 20818626
TI  - Nanoscale engineering and optical addressing of single spins in diamond.

PMID- 20818627
TI  - Lifting and sorting of charged Au nanoparticles by electrostatic forces in atomic
      force microscopy.

PMID- 20818628
TI  - Resonance-coupling-based plasmonic switches.

PMID- 20818629
TI  - The effect of thermal gradients in SERS spectroscopy.

PMID- 20818630
TI  - The DNA damage response--repair or despair?
AB  - The term "the DNA damage response" (DDR) encompasses a sophisticated array of
      cellular initiatives set in motion as cells are exposed to DNA-damaging events.
      It has been known for over half a century that all organisms have the ability to
      restore genomic integrity through DNA repair. More recent discoveries of signal
      transduction pathways linking DNA damage to cell cycle arrest and apoptosis have
      greatly expanded our views of how cells and tissues limit mutagenesis and
      tumorigenesis. DNA repair not only plays a pivotal role in suppressing
      mutagenesis but also in the reversal of signals inducing the stress response. If
      repair is faulty or the cell is overwhelmed by damage, chances are that the cell
      will despair and be removed by apoptosis. This final fate is determined by
      intricate cellular dosimeters that are yet to be fully understood. Here, key
      findings leading to our current view of DDR are discussed as well as potential
      areas of importance for future studies.

PMID- 20818631
TI  - Diastereo- and enantioselective hydrogenation of alpha-amino-beta-keto ester
      hydrochlorides catalyzed by an iridium complex with MeO-BIPHEP and NaBArF:
      catalytic cycle and five-membered chelation mechanism of asymmetric
      hydrogenation.
AB  - The development of Ir-catalyzed asymmetric hydrogenation of alpha-amino-beta-keto
      ester hydrochlorides is described. This reaction proceeds through a dynamic
      kinetic resolution to produce anti-beta-hydroxy-alpha-amino acid esters in a high
      diastereo- and enantioselective manner. Mechanistic studies have revealed that
      this unique asymmetric hydrogenation proceeds through reduction of the ketone
      moiety via the five-membered transition state involving the chelation between the
      oxygen of the ketone and the nitrogen of the amine function. The relationship
      studies between the hydrogen pressure and the stereoselectivity have disclosed
      two mechanisms dependent on hydrogen pressure. Under low hydrogen pressure (<15
      atm), the reaction rate proportionally increased with the hydrogen pressure.
      However, under the high hydrogen conditions, the reaction rate exponentially
      accelerated along with the increasing hydrogen pressure, which suggests the
      participation of two or more of hydrogen atoms.

PMID- 20818632
TI  - DNA ends: just the beginning (Nobel lecture).

PMID- 20818633
TI  - Flexibility in a metal-organic framework material controlled by weak dispersion
      forces: the bistability of MIL-53(Al).

PMID- 20818634
TI  - [4+2] cycloaddition reaction of cyclic alkyne-{Co2(CO)6} complexes with dienes.

PMID- 20818636
TI  - C-F activation of fluorobenzene by silylium carboranes: evidence for incipient
      phenyl cation reactivity.

PMID- 20818635
TI  - Cross-coupling in a flow microreactor: space integration of lithiation and
      Murahashi coupling.

PMID- 20818637
TI  - Hypersensitive-like response to the pore-former peptaibol alamethicin in
      Arabidopsis thaliana.
AB  - In Arabidopsis thaliana cell cultures, the peptaibol alamethicin induced a form
      of active cell death that was associated with cell shrinkage and DNA
      fragmentation. The transfer of mature A. thaliana plants from a peptide-free
      medium to a medium containing a moderate concentration of alamethicin caused the
      development of lesions in leaves after a few days. These lesions were
      characterized by cell death, deposition of callose, production of autofluorescent
      phenolic compounds, and transcription of defense genes, just like in the
      hypersensitive response to a pathogen attack. The induction of defense-like
      responses in Arabidopsis by other membrane-disrupting peptides was also
      evaluated. The peptides selected for comparison included the natural
      antimicrobial melittin and the peptaibol ampullosporin A, as well as synthetic
      analogues of the peptaibols cervinin and trichogin. The response amplitude in A.
      thaliana increased with the peptaibol's ability to permeabilize biological
      membranes through a pore-forming mechanism and was strongly associated with their
      content in the helicogenic alpha-aminoisobutyric acid residue.

PMID- 20818638
TI  - Synthesis and characterization of oriented glyco-capturing macroligand.
AB  - An oriented glyco-capturing macroligand was synthesized by site-specific
      immobilization of an O-cyanate chain-end-functionalized boronic acid containing
      polymer (boropolymer) onto an amine surface. The O-cyanate chain-end
      functionalized boropolymer was synthesized by arylamine-initiated cyanoxyl
      mediated free-radical polymerization in a one-pot fashion. The chain-end O
      cyanate was confirmed by (13)C NMR spectroscopy. The specific carbohydrate
      binding capacity of the boropolymer was evaluated by an alizarin red S assay.
      Oriented and covalent immobilization of the O-cyanate chain-end-functionalized
      boropolymer onto the amine-modified solid surfaces and its specific glyco
      capturing capacity were confirmed by the quartz crystal microbalance (QCM) and
      atomic force microscopy (AFM) techniques. The oriented multivalent glyco
      capturing ligand can be used for efficient carbohydrate and glycoconjugate
      purification and identification, and thus is expected to constitute a core
      strategy of glycomics and glycoproteomics and carbohydrate-sensing applications.

PMID- 20818639
TI  - Electrophosphorescent heterobimetallic oligometallaynes and their applications in
      solution-processed organic light-emitting devices.
AB  - By combining the iridium(III) ppy-type complex (Hppy=2-phenylpyridine) with a
      square-planar platinum(II) unit, some novel phosphorescent oligometallaynes
      bearing dual metal centers (viz. Ir(III) and Pt(II)) were developed by combining
      trans-[Pt(PBu(3))(2)Cl(2)] with metalloligands of iridium possessing bifunctional
      pendant acetylene groups. Photophysical and computational studies indicated that
      the phosphorescent excited states arising from these oligometallaynes can be
      ascribed to the triplet emissive Ir(III) ppy-type chromophore, owing to the
      obvious trait (such as the longer phosphorescent lifetime at 77 K) also conferred
      by the Pt(II) center. So, the two different metal centers show a synergistic
      effect in governing the photophysical behavior of these heterometallic
      oligometallaynes. The inherent nature of these amorphous materials renders the
      fabrication of simple solution-processed doped phosphorescent organic light
      emitting diodes (PHOLEDs) feasible by effectively blocking the close-packing of
      the host molecules. Saliently, such a synergistic effect is also important in
      affording decent device performance for the solution-processed PHOLEDs. A maximum
      brightness of 3,356 cd m(-2) (or 2,708 cd m(-2)), external quantum efficiency of
      0.50% (or 0.67%), luminance efficiency of 1.59 cd A(-1) (or 1.55 cd A(-1)), and
      power efficiency of 0.60 Lm W(-1) (or 0.55 Lm W(-1)) for the yellow (or orange)
      phosphorescent PHOLEDs can be obtained. These results show the great potential of
      these bimetallic emitters for organic light-emitting diodes.

PMID- 20818642
TI  - Sodium/myo-inositol cotransporter 1 and myo-inositol are essential for
      osteogenesis and bone formation.
AB  - myo-Inositol (MI) plays an essential role in several important processes of cell
      physiology, is involved in the neural system, and provides an effective treatment
      for some psychiatric disorders. Its role in osteogenesis and bone formation
      nonetheless is unclear. Sodium/MI cotransporter 1 (SMIT1, the major cotransporter
      of MI) knockout (SMIT1(-/-)) mice with markedly reduced tissue MI levels were
      used to characterize the essential roles of MI and SMIT1 in osteogenesis. SMIT1(
      /-) embryos had a dramatic delay in prenatal mineralization and died soon after
      birth owing to respiratory failure, but this could be rescued by maternal MI
      supplementation. The rescued SMIT1(-/-) mice had shorter limbs, decreased bone
      density, and abnormal bone architecture in adulthood. Deletion of SMIT1 resulted
      in retarded postnatal osteoblastic differentiation and bone formation in vivo and
      in vitro. Continuous MI supplementation partially restored the abnormal bone
      phenotypes in adult SMIT1(-/-) mice and strengthened bone structure in SMIT1(+/+)
      mice. Although MI content was much lower in SMIT1(-/-) mesenchymal cells (MSCs),
      the I(1,4,5)P(3) signaling pathway was excluded as the means by which SMIT1 and
      MI affected osteogenesis. PCR expression array revealed Fgf4, leptin, Sele, Selp,
      and Nos2 as novel target genes of SMIT1 and MI. SMIT1 was constitutively
      expressed in multipotential C3H10T1/2 and preosteoblastic MC3T3-E1 cells and
      could be upregulated during bone morphogenetic protein 2 (BMP-2)-induced
      osteogenesis. Collectively, this study demonstrated that deficiency in SMIT1 and
      MI has a detrimental impact on prenatal skeletal development and postnatal bone
      remodeling and confirmed their essential roles in osteogenesis, bone formation,
      and bone mineral density (BMD) determination.

PMID- 20818641
TI  - Pharmacogenetic tests in cancer chemotherapy: what physicians should know for
      clinical application.
AB  - Significant efforts to develop pharmacogenomic predictors have been made to guide
      more effective and safer chemotherapy. Although a considerable amount of data has
      been generated from numerous experimental or clinical studies, there is a large
      gap between pharmacogenomic knowledge and clinical application. This review will
      focus on eight pharmacogenetic tests including TYMS, DPYD, UGT1A1, CYP2D6, EGFR,
      KRAS, FCGR3A, and BRCA1/2 to predict toxicity or response to commonly used
      chemotherapeutic agents. We will discuss the current level of evidence, if the
      current pharmacogenetic tests are appropriate for clinical application, and how
      to integrate the pharmacogenomic information into routine clinical practice.

PMID- 20818643
TI  - Competing roles of phenotype and genotype in prognosis of breast carcinoma: enter
      the RNA expression profile.

PMID- 20818645
TI  - Likelihood inference for a two-stage design with treatment selection.
AB  - A conditional likelihood-based approach is proposed to construct confidence
      intervals for the parameters of interest in a two-stage design with treatment
      selection after the first stage. Both a Wald confidence interval and a confidence
      interval based on inverting the likelihood ratio test are proposed. The operating
      characteristics of these confidence intervals: the coverage probabilities and
      average confidence interval lengths, as well as the average bias and mean-square
      error of the corresponding point estimates, compare favorably with other
      available techniques. Possible extensions and an alternative unconditional
      approach based on the likelihood with missing at random mechanism are also
      briefly described.

PMID- 20818644
TI  - Anticancer efficacy of Apo2L/TRAIL is retained in the presence of high and
      biologically active concentrations of osteoprotegerin in vivo.
AB  - Osteoprotegerin (OPG) is a secreted member of the tumor necrosis factor (TNF)
      receptor superfamily that binds to the ligand for receptor activator of nuclear
      factor kappaB (RANKL) and inhibits bone resorption. OPG can also bind and inhibit
      the activity of the TNF-related apoptosis-inducing ligand (Apo2L/TRAIL), raising
      the possibility that the anticancer efficacy of soluble Apo2L/TRAIL may be
      abrogated in the bone microenvironment where OPG expression is high. In this
      study we used a murine model of breast cancer growth in bone to evaluate the
      efficacy of recombinant soluble Apo2L/TRAIL against intratibial tumors that were
      engineered to overexpress native full-length human OPG. In vitro, OPG
      overexpressing breast cancer cells were protected from Apo2L/TRAIL-induced
      apoptosis, an effect that was reversed with the addition of soluble RANKL or
      neutralizing antibodies to OPG. In vivo, mice injected intratibially with cells
      containing the empty vector developed large osteolytic lesions. In contrast, OPG
      overexpression preserved the integrity of bone and prevented breast cancer
      induced bone destruction. This effect was due primarily to the complete absence
      of osteoclasts in the tibias of mice inoculated with OPG-transfected cells,
      confirming the biologic activity of the transfected OPG in vivo. Despite the
      secretion of supraphysiologic levels of OPG, treatment with Apo2L/TRAIL resulted
      in strong growth inhibition of both empty vector and OPG-overexpressing
      intratibial tumors. While Apo2L/TRAIL-induced apoptosis may be abrogated in vitro
      by OPG overexpression, the in vivo anticancer efficacy of recombinant soluble
      Apo2L/TRAIL is retained in the bone microenvironment even in the presence of
      biologically active OPG at supraphysiologic concentrations.

PMID- 20818647
TI  - Photo-curable polymer blend dielectrics for advancing organic field-effect
      transistor applications.

PMID- 20818646
TI  - Alkyl passivation and amphiphilic polymer coating of silicon nanocrystals for
      diagnostic imaging.
AB  - A method to produce biocompatible polymer-coated silicon nanocrystals for medical
      imaging is shown. Silica-embedded Si nanocrystals are formed by HSQ thermolysis.
      The nanocrystals are then liberated from the oxide and terminated with Si-H bonds
      by HF etching, followed by alkyl monolayer passivation by thermal
      hydrosilylation. The Si nanocrystals have an average diameter of 2.1 nm +/- 0.6
      nm and photoluminesce with a peak emission wavelength of 650 nm, which lies
      within the transmission window of 650-900 nm that is useful for biological
      imaging. The hydrophobic Si nanocrystals are then coated with an amphiphilic
      polymer for dispersion in aqueous media with the pH ranging between 7 and 10 and
      an ionic strength between 30 mM and 2 M, while maintaining a bright and stable
      photoluminescence and a hydrodynamic radius of only 20 nm. Fluorescence imaging
      of polymer-coated Si nanocrystals in biological tissue is demonstrated, showing
      the potential for in vivo imaging.

PMID- 20818648
TI  - Monolithic integration of multi-color organic LEDs by grayscale lithography.

PMID- 20818649
TI  - Intraoperative frozen section analysis of sentinel lymph nodes in breast cancer
      patients: a meta-analysis and single-institution experience.
AB  - BACKGROUND: Accurate intraoperative pathologic examination of sentinel lymph
      nodes (SLNs) has been an important tool that can reduce the need for reoperations
      in patients with SLN-positive breast cancer. The objective of the current study
      was to determine the accuracy of intraoperative frozen section (IFS) of SLNs
      during breast cancer surgery. METHODS: The authors retrospectively reviewed the
      records of 326 patients with breast cancer who underwent IF analysis of SLNs at a
      single institution. Then, they conducted a meta-analysis that included 47
      published studies of IFS of SLNs in patients with breast cancer. RESULTS:
      Hematoxylin and eosin (H&E) staining revealed metastasis in SLNs in 99 patients
      (30.4%), including 61 patients with macrometastasis (MAM) (>2 mm) (the MAM group)
      and 38 patients with micrometastasis (Mi) or isolated tumor cell (ITC) deposits
      (the Mi/ITC group). The overall sensitivity of the institutional series was 60.6%
      (60 of 99 patients), and overall specificity was 100% (227 of 227 true
      negatives). The sensitivity of IFS was significantly lower in the Mi/ITC group
      (28.9%) than in the MAM group (80.3%; P < .0001). According to the meta-analysis
      of published studies and data from the author's institution (47 studies, for a
      total of 13,062 patients who underwent SLN dissection with IFS of SLNs), the mean
      sensitivity was 73%, and the mean specificity was 100%. The mean sensitivity was
      94% for the MAM group and 40% for the Mi/ITC group. CONCLUSIONS: IFS of SLNs was
      more reliable for detecting MAM than for detecting Mi/ITC deposits. It lacked
      sufficient accuracy to rule out Mi/ITC deposits.

PMID- 20818650
TI  - Integrative genomic characterization and a genomic staging system for
      gastrointestinal stromal tumors.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GISTs) historically were grouped
      with leiomyosarcomas (LMSs) based on their morphologic similarities; however,
      recently, GIST was established unequivocally as a distinct type of sarcoma based
      on its molecular features and response to imatinib treatment. METHODS: To gain
      further insight into the genomic differences between GISTs and LMSs, the authors
      mapped gene copy number aberrations (CNAs) in 42 GISTs and 30 LMSs and integrated
      the results with gene expression profiles. RESULTS: Distinct patterns of CNAs
      were revealed between GISTs and LMSs. Losses in 1p, 14q, 15q, and 22q were
      significantly more frequent in GISTs than in LMSs (P < .001); whereas losses in
      chromosomes 10 and 16 and gains in 1q, 14q, and 15q (P < .001) were more common
      in LMSs. By integrating CNAs with gene expression data and clinical information,
      the authors identified several clinically relevant CNAs that were prognostic of
      survival in patients with GIST. Furthermore, GISTs were categorized into 4 groups
      according to an accumulating pattern of genetic alterations. Many key cellular
      pathways were expressed differently in the 4 groups, and the patients in each
      group had increasingly worse prognoses as the extent of genomic alterations
      increased. CONCLUSIONS: Based on the current findings, the authors proposed a new
      tumor-progression genetic staging system termed genomic instability stage to
      complement the current prognostic predictive system based on tumor size, mitotic
      index, and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT)
      mutation.

PMID- 20818651
TI  - Molecular typing of epithelial ovarian carcinomas using inflammatory markers.
AB  - BACKGROUND: Ovarian epithelial carcinomas have recently been classified as slow
      growing type I tumors and rapidly growing highly aggressive type II tumors. The
      present study sought to molecularly characterize type I and II tumors using known
      molecular markers. METHODS: Specimens from 213 patients with ovarian carcinoma
      were categorized as type I or type II, and evaluated by immunohistochemistry for
      the inflammatory markers glucose transporter protein-1 (Glut-1), inducible nitric
      oxide synthase (iNOS), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and
      nuclear factor kappa B. Statistical analysis was performed to investigate whether
      these molecular markers could distinguish between type I and type II tumors.
      Kaplan-Meier survival curves and COX regression analysis were used to determine
      the prognostic effect of these markers on survival in the 2 types of tumors.
      RESULTS: Overexpression of COX-1, COX-2, iNOS, and Glut-1 was significantly
      higher in type II tumors (P < .05). Women with type II tumors had a poorer median
      survival (60 months) as compared with those with type I tumors (141 months) (P =
      .0001). Multivariate analysis revealed type II tumors, late stage, and age >60
      years as significant predictors of poor survival. For type II tumors, median
      survival of patients with tumors overexpressing COX-2 was 44 compared with 85
      months for those with tumors with low COX-2 expression (P = .029). Looking at
      both type I and II tumors, the number of markers simultaneously overexpressed in
      each tumor was a significant predictor of poor patient survival (P = .005).
      CONCLUSIONS: The present study demonstrates that the new proposed histologic
      classification of ovarian epithelial carcinomas correlates with a distinct
      expression of inflammatory pathway proteins. High expression of these markers may
      explain the different biologic behavior of these 2 tumor types and provide
      targets for therapy.

PMID- 20818652
TI  - Subconjunctival carboplatin and systemic topotecan treatment in preclinical
      models of retinoblastoma.
AB  - BACKGROUND: The authors demonstrated previously that the combination of topotecan
      (TPT) and carboplatin (CBP) was more effective than current chemotherapeutic
      combinations used to treat retinoblastoma in an orthotopic xenograft model.
      However, systemic coadministration of these agents is not ideal, because both
      agents cause dose-limiting myelosuppression in children. METHODS: To overcome the
      toxicity associated with systemic TPT and CBP, the authors explored
      subconjunctival delivery of TPT or CBP in an orthotopic xenograft model and in a
      genetic mouse model of retinoblastoma (Chx10-Cre;Rb(lox/lox);p107(-/
      );p53(lox/lox)). The effects of combined subconjunctival CBP (CBP(subcon)) and
      systemic TPT (TPT(syst)) were compared with the effects of combined TPT(subcon)
      and CBP(syst.) at clinically relevant dosages. RESULTS: Pharmacokinetic and tumor
      response studies, including analyses of ocular and hematopoietic toxicity,
      revealed that CBP(subcon)/TPT(syst) was more effective and had fewer side effects
      than TPT(subcon)/CBP(syst). CONCLUSIONS: For the first time, retinoblastoma was
      ablated and long-term vision was preserved in a mouse model by using a clinically
      relevant chemotherapy regimen. These results eventually may be translated into a
      clinical trial for children with this debilitating cancer.

PMID- 20818653
TI  - Polysomnographic diagnosis of idiopathic REM sleep behavior disorder.
AB  - The presence of either excessive tonic chin EMG activity during REM sleep, or
      excessive phasic submental or limb EMG twitching is required to diagnose REM
      sleep behavior disorder (RBD). The aim was to identify cut-off values and to
      assess the sensitivity and specificity of these values taken separately or
      combined to diagnose idiopathic RBD patients. Eighty patients presenting with a
      clinical diagnosis of idiopathic RBD and 80 age- and gender-matched normal
      controls were studied in the sleep laboratory. Receiver operating characteristic
      curves were drawn to find optimal cut-off values for three REM sleep EMG
      parameters. Tonic and phasic EMG activity were measured in the chin, but not in
      the limbs. Videos were examined during the recording but were not systematically
      reviewed by the authors. Total correct classification of 81.9% was found for
      tonic chin EMG density >=30%; 83.8% for phasic chin EMG density >=15% and 75.6%
      for >=24 leg movements per hour of REM sleep. Five patients did not fulfill any
      of these three polysomnographic (PSG) criteria. Conversely, one subject of the
      control group met the PSG criteria for RBD. This study estimates the diagnostic
      value of a visual scoring method for the diagnosis of idiopathic RBD and
      establishes cut-off values to be used in clinical and research set-ups. For the
      five RBD patients who did not show chin EMG abnormalities, it cannot be excluded
      that they had increased phasic EMG activity in the upper limbs and presented
      visible motor activity.

PMID- 20818654
TI  - Novel technology to provide an enriched therapeutic cell concentrate from bone
      marrow aspirate.
AB  - Current strategies to repair fractures rely on orthopaedic surgeons harvesting
      bone from one area of the body, typically pelvis and transferring it to the
      fracture site. The amount of tissue available is therefore limited, requiring a
      second surgical procedure and often causing the patient long term pain. An
      alternative approach is utilise therapeutic cells contained within bone marrow
      aspirate during the primary procedure. The number of therapeutic cells within a
      fresh aspirate is insufficient to provide clinically acceptable bone healing in a
      timescale that is satisfactory to the surgeon and the patient. Therefore methods
      to efficiently concentrate bone marrow in the clinical setting are required.
      Centrifugation is the current method of choice but has limitations in that it
      requires large capital equipment, servicing and there are potential issues of
      tissue contamination. We have developed a novel, acoustically-assisted filtration
      device that addresses these limitations, delivering a concentrated bone marrow in
      a point of care, single use, fully disposable, compact device. An additional
      advantage is that the level of concentration required can be specified by the end
      user. The resulting bone marrow concentrate has been characterised in terms of
      cell number, viability and osteogenic potential using flow cytometry and alkaline
      phosphatase assay. When compared to recent clinical studies using bone marrow to
      repair non-union fractures, the findings from our work suggest that the bone
      marrow concentrate is likely to be highly therapeutic and clinically efficacious
      as a bone fracture repair strategy. A product concept for use in the clinical
      setting is presented.

PMID- 20818655
TI  - Predominant ataxia, low ceruloplasmin, and absent K-F rings:
      hypoceruloplasminemia or Wilson's disease.

PMID- 20818656
TI  - Religiosity associated with prolonged survival in liver transplant recipients.
AB  - We tested the hypothesis that religiosity (ie, seeking God's help, having faith
      in God, trusting in God, and trying to perceive God's will in the disease) is
      associated with improved survival in patients with end-stage liver disease who
      have undergone orthotopic liver transplantation. We studied a group of 179
      candidates for liver transplantation who responded to a questionnaire on
      religiosity during the pretransplant psychological evaluation and underwent
      transplantation between 2004 and 2007. The demographic data, educational level,
      employment status, clinical data, and results of the questionnaire were compared
      with the survival of patients during follow-up, regardless of the cause of any
      deaths. Factorial analysis of responses to the questionnaire revealed 3 main
      factors: searching for God (active), waiting for God (passive), and fatalism. The
      consistency of the matrix was very high (consistency index = 0.92). Eighteen
      patients died during follow-up (median time = 21 months). In multivariate
      analysis, only the searching for God factor [hazard ratio (HR) = 2.95, 95%
      confidence interval (CI) = 1.05-8.32, chi(2) = 4.205, P = 0.040] and the
      posttransplant length of stay in the intensive care unit (HR = 1.05, 95% CI =
      1.01-1.08, chi(2) = 8.506, P = 0.035) were independently associated with
      survival, even after adjustments for the waiting for God factor, fatalism, age,
      sex, marital status, employment, educational level, viral etiology, Child-Pugh
      score, serum creatinine level, time from the questionnaire to transplantation,
      donor age, and intraoperative bleeding. Patients who did not present the
      searching for God factor were younger than those who did, but they had shorter
      survival times (P = 0.037) and a 3-fold increased relative risk of dying (HR =
      3.01, 95% CI = 1.07-8.45). In conclusion, religiosity is associated with
      prolonged survival in patients undergoing liver transplantation.

PMID- 20818658
TI  - Olfactory heterogeneity in LRRK2 related Parkinsonism.
AB  - LRRK2 mutations can cause familial and sporadic Parkinson's disease (PD) with
      Lewy-body pathology at post-mortem. Studies of olfaction in LRRK2 are sparse and
      incongruent. We applied a previously validated translation of the 16 item smell
      identification test from Sniffin' Sticks (SS-16) to 14 parkinsonian carriers of
      heterozygous G2019S LRRK2 mutation and compared with 106 PD patients and 118
      healthy controls. The mean SS-16 score in LRRK2 was higher than in PD (p < 0.001,
      95% CI for beta = -4.7 to -1.7) and lower than in controls (p = 0.007, 95% CI for
      beta = +0.6 to +3.6). In the LRRK2 group, subjects with low scores had
      significantly more dyskinesia. They also had younger age of onset, longer disease
      duration, and reported less frequently a family history of PD, but none of these
      other differences reached significance. Odor identification is diminished in
      LRRK2 parkinsonism but not to the same extent as in idiopathic PD.

PMID- 20818657
TI  - Achieving reliability and high accuracy in automated protein docking: ClusPro,
      PIPER, SDU, and stability analysis in CAPRI rounds 13-19.
AB  - Our approach to protein-protein docking includes three main steps. First, we run
      PIPER, a rigid body docking program based on the Fast Fourier Transform (FFT)
      correlation approach, extended to use pairwise interactions potentials. Second,
      the 1000 best energy conformations are clustered, and the 30 largest clusters are
      retained for refinement. Third, the stability of the clusters is analyzed by
      short Monte Carlo simulations, and the structures are refined by the medium-range
      optimization method SDU. The first two steps of this approach are implemented in
      the ClusPro 2.0 protein-protein docking server. Despite being fully automated,
      the last step is computationally too expensive to be included in the server. When
      comparing the models obtained in CAPRI rounds 13-19 by ClusPro, by the refinement
      of the ClusPro predictions and by all predictor groups, we arrived at three
      conclusions. First, for the first time in the CAPRI history, our automated
      ClusPro server was able to compete with the best human predictor groups. Second,
      selecting the top ranked models, our current protocol reliably generates high
      quality structures of protein-protein complexes from the structures of separately
      crystallized proteins, even in the absence of biological information, provided
      that there is limited backbone conformational change. Third, despite occasional
      successes, homology modeling requires further improvement to achieve reliable
      docking results.

PMID- 20818659
TI  - Clinical course of the first Asian family with Parkinsonism related to SNCA
      triplication.
AB  - Triplication of SNCA is a rare cause of familial Parkinson's disease compared
      with duplication. Its clinical course is believed to be more robust than
      duplication, though it is uncertain. Marked as the first among the Asian
      population, we identified a Japanese family (paternal grandfather, father, and
      son) with SNCA triplication based on genetic and clinical analyses. The proband
      had a completely triplicated region including SNCA. This allele did not share any
      common haplotypes with those of previously reported Japanese families with SNCA
      duplication. Clinical analysis indicated early onset, rapidly progressive
      parkinsonism with mild levodopa response. Further studies are needed to clarify
      the gene dose effect of SNCA.

PMID- 20818660
TI  - How orientational order governs collectivity of folded proteins.
AB  - The past decade has witnessed the development and success of coarse-grained
      network models of proteins for predicting many equilibrium properties related to
      collective modes of motion. Curiously, the results are usually robust toward the
      different cutoff distances used for constructing the residue networks from the
      knowledge of the experimental coordinates. In this study, we present a
      systematical study of network construction and their effect on the predicted
      properties. Probing bond orientational order around each residue, we propose a
      natural partitioning of the interactions into an essential and a residual set. In
      this picture, the robustness originates from the way with which new contacts are
      added, so that an unusual local orientational order builds up. These residual
      interactions have a vanishingly small effect on the force vectors on each
      residue. The stability of the overall force balance then translates into the
      Hessian as small shifts in the slow modes of motion and an invariance of the
      corresponding eigenvectors. We introduce a rescaled version of the Hessian matrix
      and point out a link between the matrix Frobenius norm based on spectral
      stability arguments and orientational local order. A recipe for the optimal
      choice of partitioning the interactions into essential and residual components is
      prescribed. Implications for the study of biologically relevant properties of
      proteins are discussed with specific examples.

PMID- 20818661
TI  - Fluctuations of backbone torsion angles obtained from NMR-determined structures
      and their prediction.
AB  - Protein molecules exhibit varying degrees of flexibility throughout their three
      dimensional structures. Protein structural flexibility is often characterized by
      fluctuations in the Cartesian coordinate space. On the other hand, the protein
      backbone can be mostly defined by two torsion angles phi and psi only. We
      introduce a new flexibility descriptor, backbone torsion-angle fluctuation
      derived from the variation of backbone torsion angles from different NMR models.
      The torsion-angle fluctuations correlate with mean-squared spatial fluctuations
      derived from the same collection of NMR models. We developed a neural-network
      based real-value predictor based on sequence information only. The predictor
      achieved ten-fold cross-validated correlation coefficients of 0.59 and 0.60, and
      mean absolute errors of 22.7 degrees  and 24.3 degrees  for the angle fluctuation
      of phi and psi, respectively. This predictor is expected to be useful for
      function prediction and protein structure prediction when predicted torsion
      angles are used as restraints. Both sequence- and structure-based prediction of
      torsion-angle fluctuation will be available at
      http://sparks.informatics.iupui.edu within the SPINE-X package.

PMID- 20818662
TI  - Carbidopa/levodopa pharmacy errors in Parkinson's disease.
AB  - Outpatient pharmacy errors are common, but little is known about their occurrence
      in Parkinson's disease (PD). We prospectively studied carbidopa/levodopa pharmacy
      errors in a cohort of PD outpatients. Over 1 year, pharmacy errors occurred in
      8/73 (11%) subjects treated with this medication, producing adverse drug events
      (ADEs) in 7/8 (87.5%) and increased healthcare utilization in 6/8 (75%) cases.
      The most common errors were substitution of controlled-release for immediate
      release carbidopa/levodopa 25/100 mg (5/8; 62.5%) or dispensation of the wrong
      carbidopa/levodopa dosage (2/8; 25%). All errors involved ongoing prescriptions,
      including three interpharmacy transfers. Three subjects (37.5%) questioned
      pharmacy staff about the change in appearance of the tablets, but the error was
      corrected in only 1/3 of these cases. Carbidopa/levodopa outpatient pharmacy
      errors are a common, preventable cause of morbidity and excessive healthcare
      utilization in PD. Education of healthcare providers, patients, and pharmacy
      staff is warranted to reduce these errors and associated ADEs.

PMID- 20818663
TI  - Novel COL4A1 mutations associated with HANAC syndrome: a role for the triple
      helical CB3[IV] domain.
AB  - The COL4A1 gene encodes the alpha1-chain of type IV collagen, which is
      ubiquitously expressed in basement membranes. Mutations in COL4A1 have been
      reported in autosomal-dominant porencephaly and in patients with symptomatic
      small vessel brain disease, inconstantly associated with eye defects. We have
      previously reported three COL4A1 mutations associated with a systemic phenotype
      that we called HANAC (Hereditary Angiopathy, Nephropathy, Aneurysms, and Cramps).
      We carried out a clinical and genetic study of three families presenting with
      characteristic features of HANAC syndrome. Common systemic signs included
      arterial retinal tortuosity and muscle cramps, with a variable combination of
      small vessel brain disease, Raynaud phenomena, and kidney defects. Three novel
      COL4A1 missense substitutions are described, which affect highly conserved
      glycine residues within the collagenous domain of the protein. All six known
      mutations associated with the HANAC phenotype are localized within the CB3[IV]
      fragment of COL4A1, which encompasses major integrin-binding sites. Our results
      confirm that HANAC syndrome is a distinct clinical entity within the COL4A1
      related disorders, which is characterized by systemic involvement and usually
      asymptomatic brain disease. The restricted distribution of COL4A1 mutations
      within the CB3[IV] region is a characteristic of the reports of patients with
      HANAC, which suggests that abnormal cell-type IV collagen interactions may
      underlie the systemic defects observed in this syndrome.

PMID- 20818664
TI  - Magnetic resonance imaging findings of shoulders in Parkinson's disease.
AB  - The aim of this study is to evaluate shoulder disturbances in Parkinson's disease
      (PD) patients using magnetic resonance imaging (MRI) which is the best tool in
      the demonstration of complex shoulder pathologies; and to determine probable
      relations between shoulder pathologies and PD clinical features. Twenty-eight PD
      patients with a total of 56 shoulders were used as the study group while 13 age
      matched cases with 26 shoulders were used as the control group (CG) in the study.
      Both patients with PD and the CG underwent shoulder MRI. The Hoehn and Yahr (H&Y)
      disability scale and Unified Parkinson's Disease Rated Scale (UPDRS) were used to
      determine the severity of the disease. Our results showed that patients with full
      thickness supraspinatus (SSP) tear have statistically significant higher UPDRS (P
      = 0.012), tremor (P = 0.023), rigidity (P = 0.023), and total (P = 0.002) scores.
      Mild group patients (P = 0.045) showed significantly higher frequency resting
      tremor and subcoracoid effusion than those of severe group patients (P = 0.002).
      Subcoracoid effusion was observed in patients with significantly higher UPDRS (P
      = 0.045) and rigidity (P = 0.022) scores. When the resting tremor and subcoracoid
      effusion groups were compared according to the severity of the resting tremor but
      not according to the H&Y, higher frequency of full-thickness tear in SSP tendon
      was detected in the group of resting tremor (P = 0.053). Longer duration of
      disease was also observed in patients with full-thickness SSP tear (P = 0.029)
      and acromioclavicular joint changes (P = 0.018). Higher UPDRS, tremor, rigidity
      and total scores and longer PD duration appear as the predisposing factors for
      the development of shoulder disturbances in PD in this study.

PMID- 20818665
TI  - Fibrocystic disease of liver and pancreas; under-recognized features of the X
      linked ciliopathy oral-facial-digital syndrome type 1 (OFD I).
AB  - OFD I is an X-linked dominant male-lethal ciliopathy characterized by prominent
      external features including oral clefts, hamartomas or cysts of the tongue, and
      digital anomalies. Although these external features are easy to recognize and
      often lead to diagnosis in early childhood, visceral findings in OFD I,
      especially the fibrocystic liver and pancreas disease, are under-recognized. In
      addition, while the occurrence of polycystic kidney disease (PKD) in OFD I is
      well known, few patients are evaluated and monitored for this complication. We
      report on two adult females diagnosed with OFD I in infancy, but not evaluated
      for visceral involvement. In adulthood, they were incidentally found to have
      severe hypertension and chronic renal insufficiency due to undiagnosed PKD. A
      pancreatic cystic lesion, also discovered incidentally, was thought to be
      malignant and led to consideration of major surgery. We present NIH evaluations,
      including documentation of OFD I mutations, extreme beading of the intrahepatic
      bile ducts, pancreatic cysts, and tabulate features of reported OFD I cases
      having hepatic, pancreatic, and renal cystic disease. Liver and pancreas are not
      routinely evaluated in OFD I patients. Increased awareness and lifelong
      monitoring of visceral complications, particularly involving the liver, pancreas,
      and kidney, are essential for timely and accurate treatment.

PMID- 20818666
TI  - Impaired postural stability as a marker of premanifest Huntington's disease.
AB  - Subtle changes in fine motor control have been observed in individuals who carry
      the Huntington's disease (HD) mutation but have not yet manifested symptoms,
      referred to as premanifest HD (preHD). However, few studies have examined gross
      motor impairments in this population. This study sought to examine the role of
      sensory involvement in maintaining postural stability during the premanifest and
      manifest stages of HD using computerized dynamic posturography. Eleven HD
      participants, 22 preHD subdivided into "preHD Near" (<5 years from estimated
      clinical onset) and "preHD Far" (>5 years from estimated clinical onset), and 17
      nongene carriers (NGC) completed a sensory organization test (SOT) to assess
      postural control when vestibular, visual, and somatosensory information was
      systematically degraded. The HD group demonstrated greater postural sway than the
      NGC and preHD Far groups on all conditions including baseline, and greater
      postural sway than the preHD Near group when sensory information was manipulated.
      The preHD Near group showed significantly greater postural sway than the preHD
      Far group when visual and somatosensory information was degraded and only
      vestibular information was available and reliable for maintaining postural
      stability. The results of this study highlight subtle postural deficits in the
      face of changing sensory conditions in preHD up to 5 years before estimated
      disease onset. The findings suggest that the SOT may be a highly sensitive
      indicator of early motor impairment and subsequent phenoconversion to manifest HD
      in preHD.

PMID- 20818667
TI  - Tolerability of isradipine in early Parkinson's disease: a pilot dose escalation
      study.
AB  - Recent data suggests that isradipine, a dihydropyridine calcium channel blocker,
      is neuroprotective in preclinical models of parkinsonism. Isradipine has not been
      systematically studied in patients with Parkinson's disease (PD). The aim of this
      study was to evaluate safety and tolerability of isradipine controlled release
      (CR) in patients with early PD. Qualified subjects (n = 31) received isradipine
      CR, titrated from 5 to 20 mg daily dose over 8 weeks as tolerated. Eighty-one
      percent of subjects completed the study. Tolerability of isradipine CR was dose
      dependent: 94% for 5 mg dose; 87% for 10 mg; 68% for 15 mg; and 52% for 20 mg.
      Isradipine had no significant effect on blood pressure or PD motor disability.
      The two most common reasons for dose reduction were leg edema (7) and dizziness
      (3). There was no difference in isradipine tolerability between subjects with and
      without dopaminergic treatment, or with and without hypertension.

PMID- 20818669
TI  - Complex hyperkinetic movement disorders associated with POLG mutations.

PMID- 20818670
TI  - Brain stem pathology in Parkinson's disease: an evaluation of the Braak staging
      model.
AB  - The lower brain stem of 25 pathologically-confirmed Parkinson's disease (PD)
      cases was examined by alpha synuclein immunohistochemistry to characterize
      pathological accumulation of alpha synuclein (Lewy-type alpha-synucleinopathy,
      LTS) in the medulla oblongata, to examine differences between affected regions
      and test a proposed model of staging of pathology in PD. All cases had LTS in the
      medulla, including the dorsal motor nucleus of the vagus (dmX), when present. The
      distribution followed a consistent pattern and appeared to be concentrated in a
      tyrosine hydroxylase (TH) immunoreactive region, probably representing the dorsal
      IX/X nuclear complex and the intermediate reticular zone. LTS density was
      greatest in the dmX. A similar distribution pattern to PD was seen in 14
      incidental Lewy body disease (ILBD) cases, five derived from the Queen Square
      Brain Bank tissue collection and nine identified in separate series of 60
      neurologically-normal individuals, and in three cases with the G2019S mutation of
      LRRK2. Semiquantitative assessment showed that severity of pathology in the dmX
      was not correlated with the severity of cortical pathology. Semiquantitative
      assay of TH and ChAT peptide expression in the medulla showed that TH expression
      in PD and ILBD did not differ from controls. These findings broadly support the
      Braak hypothesis of caudo-rostral development but indicate that the extent of the
      disease in the cortex and the severity of pathology in the medulla were
      independent of one another.

PMID- 20818671
TI  - Grasping premanifest Huntington's disease - shaping new endpoints for new trials.
AB  - Future clinical trials in subjects with premanifest Huntington's disease (preHD)
      may depend on the availability of biomarkers. It was previously shown in
      symptomatic HD that, the grip force variability coefficient-of-variation (GFV-C)
      in a grasping paradigm was correlated to the Unified-Huntington's-Disease-Rating
      Scale-Total-Motor-Score (UHDRS-TMS) and increased in a 3 year follow-up study. To
      further elucidate its potential as a biomarker, we investigated whether GFV-C is
      able to detect a motor phenotype in preHD and is correlated to the genotype
      assessed by a disease-burden-score. The ability of preHD (n = 15) and symptomatic
      HD subjects (n = 20) to maintain stable grip forces, while holding an object (250
      g and 500 g), was measured and compared with the controls (n = 19). GFV-C was
      increased in preHD at 500 g, in symptomatic subjects at both weights and was
      correlated to the disease-burden-score and UHDRS-TMS. GFV-C may be a useful
      objective and quantitative marker of motor dysfunction across genetically
      diagnosed premanifest and symptomatic HD subjects.

PMID- 20818668
TI  - Solution structure and function of YndB, an AHSA1 protein from Bacillus subtilis.
AB  - The solution structure of the Bacillus subtilis protein YndB has been solved
      using NMR to investigate proposed biological functions. The YndB structure
      exhibits the helix-grip fold, which consists of a beta-sheet with two small and
      one long alpha-helix, forming a hydrophobic cavity that preferentially binds
      lipid-like molecules. Sequence and structure comparisons with proteins from
      eukaryotes, prokaryotes, and archaea suggest that YndB is very similar to the
      eukaryote protein Aha1, which binds to the middle domain of Hsp90 and induces
      ATPase activity. On the basis of these similarities, YndB has been classified as
      a member of the activator of Hsp90 ATPase homolog 1-like protein (AHSA1) family
      with a function that appears to be related to stress response. An in silico
      screen of a compound library of ~ 18,500 lipids was used to identify classes of
      lipids that preferentially bind YndB. The in silico screen identified, in order
      of affinity, the chalcone/hydroxychalcone, flavanone, and flavone/flavonol
      classes of lipids, which was further verified by 2D (1) H-(15) N HSQC NMR
      titration experiments with trans-chalcone, flavanone, flavone, and flavonol. All
      of these compounds are typically found in plants as precursors to various
      flavonoid antibiotics and signaling molecules. The sum of the data suggests an
      involvement of YndB with the stress response of B. subtilis to chalcone-like
      flavonoids released by plants due to a pathogen infection. The observed binding
      of chalcone-like molecules by YndB is likely related to the symbiotic
      relationship between B. subtilis and plants.

PMID- 20818672
TI  - Cerebellar dysfunction in progressive supranuclear palsy: a transcranial magnetic
      stimulation study.
AB  - Progressive supranuclear palsy (PSP) rarely shows cerebellar signs and symptoms
      even though the cerebellar dentate nuclei are involved pathologically. This study
      evaluates cerebellar function using transcranial magnetic stimulation (TMS) to
      determine whether subclinical cerebellar involvement is present in PSP patients.
      We studied 11 patients with PSP, 11 patients with Parkinson's disease (PD), and
      10 age-matched controls. Patients were examined with their usual medications and
      in their relative on state. Motor evoked potentials (MEPs) were recorded from the
      hand muscle. Cerebellar function was evaluated using suppressive effects of TMS
      over the cerebellum on MEPs elicited by TMS over the contralateral motor cortex,
      which we call cerebellar inhibition (CBI). Interstimulus intervals (ISIs) of 4 to
      8 ms were used, and the time course of CBI was analyzed. The CBI was reduced in
      PSP patients. By contrast, the CBI was normal in PD patients in their on state.
      Although the CBI in their off state should be examined in future studies, the
      results described herein suggest that Purkinje cells or the dentato-thalamo
      cortical pathway assessed by CBI is involved in PSP. Our results are compatible
      with the pathological findings showing severe dentate nucleus degeneration in PSP
      patients.

PMID- 20818673
TI  - CSF Abeta(42) and tau in Parkinson's disease with cognitive impairment.
AB  - We tested the hypothesis that the CSF biomarker signature associated with
      Alzheimer's disease (AD) is present in a subset of individuals with Parkinson's
      disease and Dementia (PD-D) or with PD and Cognitive Impairment, Not Dementia (PD
      CIND). We quantified CSF Abeta(42), total tau (T-tau), and phospho-tau (P181-tau)
      using commercially available kits. Samples were from 345 individuals in seven
      groups (n): Controls <=50 years (35), Controls >50 years (115), amnestic Mild
      Cognitive Impairment (aMCI) (24), AD (49), PD (49), PD-CIND (62), and PD-D (11).
      We observed expected changes in AD or aMCI compared with age-matched or younger
      controls. CSF Abeta(42) was reduced in PD-CIND (P < 0.05) and PD-D (P < 0.01),
      whereas average CSF T-tau and P181-tau were unchanged or decreased. One-third of
      PD-CIND and one-half of PD-D patients had the biomarker signature of AD. Abnormal
      metabolism of Abeta(42) may be a common feature of PD-CIND and PD-D.

PMID- 20818674
TI  - Immunogenecity of hepatitis A vaccine in pediatric patients with inflammatory
      bowel disease.
AB  - BACKGROUND: There are only a few studies on immune response to routine
      vaccinations in children with inflammatory bowel disease (IBD), despite a strong
      need for this kind of study. The aim of the study was to evaluate the
      immunogenicity of an inactivated hepatitis A vaccine (HAV) in IBD pediatric
      patients compared with healthy controls. METHODS: This was an open, prospective,
      and controlled study on anti-HAV-negative children and adolescents age 2-18 years
      with IBD. HAV using 720 enzyme-linked immunosorbent assay (ELISA) units were
      administered at 0 months and at 6-12 months. Seroconversion and geometric mean
      titers were measured after each vaccine dose. The evidence of local and systemic
      adverse effects for 3 days after the first and second dose of vaccine was
      registered. RESULTS: A total of 134 subjects (66 patients and 68 controls)
      completed the whole study course consisting of two doses of vaccine and six serum
      samples. There was no significant difference in the rate of seroconversion
      between IBD patients and controls when measured after the second dose of vaccine
      (97% versus 100%, P = 0.2407), but the rate was significantly lower in the IBD
      group when measured after the first dose (39% versus 64%, P = 0.00001). The mean
      geometric titers were statistically significantly lower in the IBD group than in
      the control group at all of the measured timepoints. There were no serious
      adverse events related to HAV during the study. CONCLUSIONS: HAV is both
      immunogenic and safe in pediatric patients with IBD.

PMID- 20818675
TI  - Bone metastases: molecular mechanisms and novel therapeutic interventions.
AB  - It has been long recognized that skeleton represents one of the most favored
      metastatic sites for common cancers like breast and prostate. During the last
      decade the molecular mechanisms that are responsible for the development of bone
      metastasis have been gradually illuminated. It appears that the bone
      microenvironment has a pivotal role in this process. Metastatic tumor cells
      interact with bone triggering a cascade of molecular events that produce
      osteolytic and/or osteoblastic phenomena. In this review, we summarize and
      discuss the most significant factors and signaling pathways implicated in bone
      colonization. Moreover, based on the recent literature and data, we foresee the
      need for designing novel agents that will efficiently disrupt these interactions
      among cancer cells and bone microenvironment, bringing hope for more effective
      treatments.

PMID- 20818677
TI  - [ Editorial. Pharmazie in unserer Zeit 5/2010].

PMID- 20818679
TI  - [Large-scale attack against Plasmodium].

PMID- 20818680
TI  - [XF-73 - a new antibacterial lead compound].

PMID- 20818681
TI  - [Plectasin - a new peptide antibiotic with high therapeutic potential].

PMID- 20818682
TI  - [The history of the discovery of nitroglycerin].

PMID- 20818683
TI  - [The pharmacology of nitric oxide and nitrates].

PMID- 20818684
TI  - [Medicinal chemistry of nitrates and PDE5 inhibitors].

PMID- 20818685
TI  - [Treatment of coronary heart disease with nitric oxide donors].

PMID- 20818686
TI  - [Nitric oxide donors in the treatment of cardiac insufficiency].

PMID- 20818687
TI  - [Mechanisms and clinical significance of nitrate tolerance].

PMID- 20818688
TI  - [Treatment of erectile dysfunction].

PMID- 20818689
TI  - [PDE5 inhibitors in the treatment of pulmonary hypertension].

PMID- 20818690
TI  - [Nitrates and PDE5 inhibitors: pharmaceutical care].

PMID- 20818709
TI  - Modulation of signal transduction in cancer cells by phytosterols.
AB  - Phytosterols are biofactors found enriched in plant foods such as seeds, grains,
      and legumes. Their dietary consumption is associated with numerous health
      benefits. Epidemiologic and experimental animal studies indicate that
      phytosterols are cancer chemopreventive agents particularly against cancers of
      the colon, breast, and prostate. Phytosterols impede oncogenesis and prevent
      cancer cell proliferation and survival. The molecular mechanisms underlying these
      beneficial actions involve effects on signal transduction processes which
      regulate cell growth and apoptosis. Phytosterols increase sphingomyelin turnover,
      ceramide formation, and liver X receptor activation. In concert, these actions
      slow cell cycle progression, inhibit cell proliferation, and activate caspase
      cascades and apoptosis in cancer cells.

PMID- 20818710
TI  - MT1-MMP and integrins: Hand-to-hand in cell communication.
AB  - Integrins are transmembrane adhesion receptors essential for cell communication
      with the environment and in particular with the extracellular matrix (ECM). ECM
      components can be processed by several enzymes; one of the largest families
      involved in this task being matrix metalloproteinases (MMPs). MT1-MMP (membrane
      type 1-matrix metalloproteinase) is a membrane-anchored MMP with important roles
      in processes such as tissue development, tumor invasion, and angiogenesis. In
      addition to its catalytic-dependent functions, MT1-MMP can interact, via its
      cytosolic tail, with intracellular components, and trigger signaling pathways
      that impact cell decisions. These features make MT1-MMP similar to integrins,
      because both are able to integrate events in the extracellular and intracellular
      milieus. Accordingly, it is probably no coincidence that MT1-MMP often associates
      and functionally cooperates with distinct integrins at specific cellular
      compartments. In this review, we discuss aspects of the molecular and functional
      interplay between MT1-MMP and integrins in distinct cellular and biological
      contexts.

PMID- 20818711
TI  - Sulforaphane induces glutathione S-transferase isozymes which detoxify aflatoxin
      B(1)-8,9-epoxide in AML 12 cells.
AB  - The aflatoxin B(1)-8,9-epoxide (AFBO) is hepatocarcinogenic intermediate of
      aflatoxin B(1) (AFB(1)) and is detoxified by glutathione S-transferases (GSTs).
      In this study, we investigated whether sulforaphane (SFN) could increase the rate
      of conjugation between AFBO and glutathione (GSH) as well as which of the GST
      isozymes were involved in the conjugation reaction. The conjugation potential was
      inhibited dose dependently with curcumin, an inhibitor of GSTs. SFN induced the
      expression of GST A3, GST A4, GST M1, GST P1, and GST T1 in alpha mouse line
      (AML) 12 cells. The cells treated with SFN (10 microM) for 12 h showed a 35-fold
      increase in conjugation potential of AFBO with GSH compared with the vehicle
      treated cell. The conjugation potential was blocked partially by transfection of
      cells with siRNAs against each of the GST isozymes. The activity of GST A3 had
      the strongest effect on the conjugation potential. SFN treatment also increased
      total GST activity detected with 1-chloro-2,4-dinitrobenzene (CDNB) up to 4.3
      fold. The induction fold was much lower than that detected with AFBO. These
      results suggest that the chemopreventive effect of SFN on the decomposition of
      AFBO is related to the upregulation of several GST isozymes genes. The increase
      of GST activity by SFN was extremely specific toward the conjugation reaction of
      AFBO compared with CDNB. Therefore, this system for detecting GST activity seems
      to be an excellent method for screening chemopreventive compounds toward AFB(1)
      toxicity.

PMID- 20818712
TI  - Granulocyte colony-stimulating factor produces a decrease in IFNgamma and
      increase in IL-4 when administrated to healthy donors.
AB  - Hematopoietic stem cells transplantation (HSCT) is the leading curative therapy
      for a variety of hematological and hereditary diseases; however, graft versus
      host disease (GVHD), an immunologic phenomenon that is favored by Th1 cytokines
      and cytotoxic cells from donors, is present frequently and is one of the most
      important causes of transplant related mortality. Peripheral blood HSCT is the
      preferred source of stem cells in almost 100% of the cases of autologous HSCT and
      in 70% of allogeneic transplants. The best mobilizing agent to get the stem cells
      out from the bone marrow is the Granulocyte-Colony Stimulating Factor (G-CSF). In
      this work, our main objective was to study a possible correlation between the
      graft cell dose and the patient's clinical outcome. We evaluated the immunologic
      changes produced by G-CSF in the lymphocyte and cytokine profiles in allogeneic
      HSC donors. HSC from twelve donors were mobilized with G-CSF at 16 microg/kg/day,
      for 5 days. Basal Peripheral Blood (BPB), Mobilized Peripheral Blood (MPB), and
      aphaeresis mononuclear cells (G-MNC) samples were taken from all donors. Using
      flow cytometry, we quantified CD19(+), CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), NK,
      NKT, DC1, and DC2 cells. Cytokines were determined by ELISA in culture
      supernatants. CD19(+) (p = 0.001), DC1 (p < 0.002) and DC2 (p < 0.001) cells were
      increased in MPB with respect to BPB. An increase in Th2 cytokines such as (IL-4)
      and a decrease in Th1 cytokines (IFNgamma, IL-2) were also found in MPB samples.
      In conclusion, Th1 and Th2 cytokines are relevant in predicting the clinical
      outcome after allogeneic peripheral blood HSCT.

PMID- 20818713
TI  - Increased risk of citrate reactions in patients with multiple myeloma during
      peripheral blood stem cell leukapheresis.
AB  - The citrate based anticoagulant ACD is commonly used in apheresis procedures. Due
      to its ability to decrease ionized calcium, citrate may cause unpleasant
      symptoms, such as paresthesias and muscle cramps, in patients undergoing
      therapeutic and donor apheresis. We noticed that patients with multiple myeloma
      (MM) undergoing autologous stem cell leukapheresis appeared to have more citrate
      reactions when compared to other patients undergoing the same procedure. A
      retrospective chart review was performed to evaluate 139 (of 151) consecutive
      patients with MM, amyloidosis, hematological and solid malignancies who had
      autologous peripheral blood stem cell collection between January 2007 and
      February 2008. Citrate reactions, ranging from mild (e.g., perioral tingling and
      parasthesias) to severe (e.g., nausea/vomiting and muscle cramps) were noted for
      35 patients. Twenty-three of 63 patients with MM had documented citrate
      reactions, which was significantly higher than those with other hematological and
      solid malignancies (37% vs. 20%; P < 0.05, Relative Risk (RR) = 1.9). The
      severities of citrate reactions were the same in both groups; approximately 50%
      of patients in each group received i.v. calcium gluconate for treatment of
      hypocalcemia. No correlation between bisphosphonate therapy and citrate reactions
      were noted in our study group. Examination of available laboratory values related
      to calcium homeostasis, liver, and renal function failed to reveal a mechanism
      for the increase in citrate reactions observed. In summary, this single
      institution retrospective study indicates that patients with MM are more
      sensitive to citrate-induced hypocalcemia during leukapheresis when compared to
      patients with other hematological and solid malignancies. Strategies for
      decreasing citrate reactions (e.g., supplemental calcium and slowing return
      rates) should be considered for patient safety and comfort, especially in the MM
      population, on a prophylactic rather than reactive basis.

PMID- 20818714
TI  - The treatment of acute liver failure with fractionated plasma separation and
      adsorption system: Experience in 85 applications.
AB  - INTRODUCTION: Artificial liver support systems represent a potential useful
      option for the treatment of liver failure. The outcomes of patients treated with
      the fractionated plasma separation and adsorption (FPSA) system are presented.
      PATIENTS AND METHODS: FPSA was performed 85 times for 27 patients (median 3
      treatments/patient) with liver failure [85.2% acute liver failure (ALF) and 14.8%
      acute-on-chronic liver failure] using the Prometheus 4008H (Fresenius Medical
      Care) unit. Citrate was used for anticoagulation. A variety of clinical and
      biochemical parameters were assessed. Comparisons between pretreatment and post
      treatment data were performed using paired t-test. RESULTS: The 85 sessions had a
      mean duration of 6 h. There were significant decreases in total bilirubin (13.18
      +/- 9.46 mg/dL vs. 9.76 +/- 7.05 mg/dL; P < 0.0001), ammonia (167.6 +/- 75 mg/dL
      vs. 120 +/- 43.8 mg/dL; P < 0.0001), blood urea nitrogen (BUN; 12.55 +/- 13.03
      mg/dL vs. 8.18 +/- 8.15 mg/dL; P < 0.0001), creatinine (0.54 +/- 0.47 mg/dL vs.
      0.46 +/- 0.37 mg/dL; P = 0.0022) levels, and in pH (7.48 +/- 0.05 vs. 7.44 +/-
      0.08; P = 0.0045). Four patients (14.8%) received liver transplantation after the
      treatments; in nine patients, transplantation was not necessary anymore (33%);
      the remaining 14 patients did not receive a transplantation because they were
      either not appropriate candidates or no organ was available. Overall survival was
      48.1% (4 transplanted and 9 treated patients). No hematological complications
      related to FPSA were observed. CONCLUSIONS: FPSA system is a safe and effective
      detoxification method for patients with liver dysfunction, including ALF. The
      system is useful as a symptomatic treatment before liver transplantation; in up
      to 1/3 of the cases, it can even be used as a sole method of treatment.

PMID- 20818715
TI  - Plerixafor mobilization leads to a lower ratio of CD34+ cells to total nucleated
      cells which results in greater storage costs.
AB  - BACKGROUND: Plerixafor (Mozobil, AMD3100) with granulocyte-colony stimulating
      factor (G-CSF) mobilizes more CD34+ cells/kg compared to G-CSF alone. Given that
      plerixafor enhances mobilization of multiple white blood cell lineages, we
      determined if more storage space is required for products collected from patients
      mobilized with plerixafor. METHODS: A review of the medical records of 15
      patients mobilized with chemotherapy and G-CSF (control) and 14 patients
      mobilized with plerixafor plus G-CSF (plerixafor) was performed. Data on
      demographics, baseline characteristics, CD34+ cells/kg, total nucleated cells,
      total mononuclear cells, total apheresis sessions, and total bags for storage
      were collected. Mean values were determined and compared using Student's t-test.
      RESULTS: We found that the proportion of CD34+ cells among total nucleated cells
      was less in the plerixafor group compared to the control group (P = 0.0427). More
      nucleated cells (10.7 x 10(10) vs. 7.1 x 10(10), P =0.0452) and mononuclear cells
      (9.7 x 10(10) vs. 5.9 x 10(10), P = 0.0059) were mobilized with plerixafor plus G
      CSF. However, there was no significant difference in CD34+ cells/kg, total CD34+
      cells or the proportion of mononuclear cells among total nucleated cells between
      the two groups. More storage bags were required for the plerixafor group compared
      to the control group (15 vs. 9, P = 0.0299). CONCLUSION: Mobilization with
      plerixafor plus G-CSF resulted in a smaller proportion of CD34+ cells collected
      and a greater number of storage bags. An increase in the number of bags required
      for stem cell storage may be logistically problematic and will also lead to
      increased costs for storage of stem cells.

PMID- 20818716
TI  - Plasma filtration in the treatment of Graves' ophthalmopathy: A randomized study.
AB  - The aim of this study was to perform a randomized study to evaluate the role of
      plasma filtration in the treatment of severe thyroid-associated ophthalmopathy
      (TAO). 20 patients were enrolled, and all patients were treated with
      methylprednisolone IV pulses. 10 randomly chosen patients were also subjected to
      plasma filtration (twice weekly in Weeks 1, 2, 4, 7, and 10). The procedure
      proved to be safe. All immunoglobulin classes as well as autoantibodies directed
      against thyroglobulin, thyroid peroxidase, and TSH receptor exhibited
      statistically significantly decreases. Some markers of cell-mediated immunity
      such as soluble antigen CD30 and monocyte chemotactic protein 1 decreased, but
      serum levels of other markers such as CD40 ligand and soluble protein Fas/Apo-1
      did not change significantly. The decrease of immunoglobulins was long lasting,
      whereas cytokine levels returned to basal values before the next apheresis.
      Although the clinical activity score (CAS) dropped in all patients, it occurred
      more rapidly in patients treated with plasma filtration. The CAS difference
      between the two groups was statistically significant (p = 0.027). The amplitude
      of visual evoked potentials improved after 3 months in the plasma filtration
      group. At the end of the study, there was no difference between patients treated
      with aphereses and the control group. Eye muscle width and proptosis measured by
      CT scan did not differ between the two groups. We conclude that apheresis can
      decrease disease activity more rapidly than standard high-dose IV glucocorticoid
      therapy. Whether this superior treatment effect could potentially avoid surgical
      procedures remains to be determined.

PMID- 20818717
TI  - Splenic rupture in a plasma cell leukemia, mobilized with G-CSF for autologous
      stem cell transplant.
AB  - Splenic rupture (SR) is a rare adverse event observed in patients treated with G
      CSF as a peripheral hematopoietic stem cell (PHSC) mobilizing agent, mostly in
      myeloma multiple and amiloidosis; to date, to our knowledge, it has not been
      previously described in plasma-cell leukemia (PCL). We report a case of a woman
      with PCL, who presented a SR after PHSC mobilization with Cyclophosphamide+G-CSF.
      The spleen removed showed hematopoietic foci and amiloid material. In the course
      of a second mobilization, 2 months after, the patient died from sepsis. We
      considered it important to report this case, in order to keep in mind the
      possibility of SR in patients with malignant gammopathy.

PMID- 20818718
TI  - Plasmapheresis in the treatment of hypertriglyceridemia-induced pancreatitis: A
      community hospital's experience.
AB  - BACKGROUND: Hyperlipidemic pancreatitis is a potentially fatal complication of
      hypertriglyceridemia (HTG). The current mainstay of treatment for the
      hypertriglyceridemia associated with pancreatitis includes heparin, insulin and
      lipid lowering agents. Experiences with plasmapheresis are limited. Here, we
      report our experience using plasmapheresis in the treatment of four patients with
      acute severe HTG-induced pancreatitis. METHODS: Four patients with acute severe
      HTG-induced pancreatitis due to severe primary hyperlipidemia exacerbated by
      secondary factors were studied. In addition to the standard treatment (insulin or
      heparin infusion), antibiotics and lipid lowering agents, two were treated within
      the first 48 hours, and two with early (<24 hours) plasmapheresis with 5%
      albumin. RESULTS: All four patients had a significant improvement in their
      triglyceride levels using plasmapheresis with an average reduction in TG levels
      of 70.4% per treatment and 89.3% with the first treatment. However, there was no
      clear relation between the use of plasmapheresis and either improvement in APACHE
      II scores, length of stay in either the ICU or overall hospital length of stay or
      in the prevention of complications secondary to severe pancreatitis, including in
      the two patients who received plasmapheresis in the first 24 hours. CONCLUSION:
      Our report showed that plasmapheresis was successful in lowering TG levels.
      However, in the absence of a comparison with standard treatment (heparin or
      insulin infusion and lipid lowering agents) the effect of plasmapheresis on
      lowering the morbidity and length of stay of patients with HTG-induced acute
      severe pancreatitis is uncertain and warrants further investigation into its
      efficacy.

PMID- 20818719
TI  - The diagnosis of autoimmune hepatitis in patients with adult-onset Still's
      disease.

PMID- 20818721
TI  - Estimation of P-value of MAX test with double triangle diagram for 2 x 3 SNP case
      control tables.
AB  - Single nucle otide polymorphisms (SNPs) are the most popular markers in genetic
      epidemiology. Multiple tests have been applied to evaluate genetic effect of
      SNPs, such as Pearson's test with two degrees of freedom, three tests with one
      degree of freedom (chi(2) tests for dominant and recessive modes and Cockran
      Armitage trend test for additive mode) as well as MAX3 test and MAX test, which
      are combination of four tests mentioned earlier. Because MAX test is a
      combination of Pearson's test of two degrees of freedom and two tests of one
      degree of freedom, the probability density function (pdf) of MAX statistics does
      not match pdf of chi(2) distribution of either one or two degrees of freedom. In
      order to calculate P-value of MAX test, we introduced a new diagram, Double
      Triangle Diagram, which was an extension of de Finetti diagram in population
      genetics which characterized all of the tests for 2 x 3 tables. In the diagram
      the contour lines of MAX statistics were consisted of elliptic curves and two
      tangent lines to the ellipses in the space. We normalized the ellipses into
      regular circles and expressed P-value of MAX test in an integral form. Although a
      part of the integral was not analytically solvable, it was calculable with
      arbitrary accuracy by dividing the area under pdf into finite rectangles. We
      confirmed that P-values from our method took uniform distribution from 0 to 1 in
      three example marginal count sets and concluded that our method was appropriate
      to give P-value of MAX test for 2 x 3 tables.

PMID- 20818722
TI  - A Bayesian approach to genetic association studies with family-based designs.
AB  - For genome-wide association studies with family-based designs, we propose a
      Bayesian approach. We show that standard transmission disequilibrium test and
      family-based association test statistics can naturally be implemented in a
      Bayesian framework, allowing flexible specification of the likelihood and prior
      odds. We construct a Bayes factor conditional on the offspring phenotype and
      parental genotype data and then use the data we conditioned on to inform the
      prior odds for each marker. In the construction of the prior odds, the evidence
      for association for each single marker is obtained at the population-level by
      estimating its genetic effect size by fitting the conditional mean model. Since
      such genetic effect size estimates are statistically independent of the effect
      size estimation within the families, the actual data set can inform the
      construction of the prior odds without any statistical penalty. In contrast to
      Bayesian approaches that have recently been proposed for genome-wide association
      studies, our approach does not require assumptions about the genetic effect size;
      this makes the proposed method entirely data-driven. The power of the approach
      was assessed through simulation. We then applied the approach to a genome-wide
      association scan to search for associations between single nucleotide
      polymorphisms and body mass index in the Childhood Asthma Management Program
      data.

PMID- 20818723
TI  - Introduction: Emerging research in mitochondrial disease.

PMID- 20818725
TI  - Bioenergetics and the epigenome: interface between the environment and genes in
      common diseases.
AB  - Extensive efforts have been directed at using genome-wide association studies
      (GWAS) to identify the genes responsible for common metabolic and degenerative
      diseases, cancer, and aging, but with limited success. While environmental
      factors have been evoked to explain this conundrum, the nature of these
      environmental factors remains unexplained. The availability of and demands for
      energy constitute one of the most important aspects of the environment. The flow
      of energy through the cell is primarily mediated by the mitochondrion, which
      oxidizes reducing equivalents from hydrocarbons via acetyl-CoA, NADH + H(+), and
      FADH(2) to generate ATP through oxidative phosphorylation (OXPHOS). The
      mitochondrial genome encompasses hundreds of nuclear DNA (nDNA)-encoded genes
      plus 37 mitochondrial DNA (mtDNA)-encoded genes. Although the mtDNA has a high
      mutation rate, only milder, potentially adaptive mutations are introduced into
      the population through female oocytes. In contrast, nDNA-encoded bioenergetic
      genes have a low mutation rate. However, their expression is modulated by histone
      phosphorylation and acetylation using mitochondrially-generated ATP and acetyl
      CoA, which permits increased gene expression, growth, and reproduction when
      calories are abundant. Phosphorylation, acetylaton, and cellular redox state also
      regulate most signal transduction pathways and activities of multiple
      transcription factors. Thus, mtDNA mutations provide heritable and stable
      adaptation to regional differences while mitochondrially-mediated changes in the
      epigenome permit reversible modulation of gene expression in response to
      fluctuations in the energy environment. The most common genomic changes that
      interface with the environment and cause complex disease must, therefore, be
      mitochondrial and epigenomic in origin.

PMID- 20818726
TI  - The neurologic manifestations of mitochondrial disease.
AB  - The nervous system contains some of the body's most metabolically demanding cells
      that are highly dependent on ATP produced via mitochondrial oxidative
      phosphorylation. Thus, the neurological system is consistently involved in
      patients with mitochondrial disease. Symptoms differ depending on the part of the
      nervous system affected. Although almost any neurological symptom can be due to
      mitochondrial disease, there are select symptoms that are more suggestive of a
      mitochondrial problem. Certain symptoms that have become sine qua non with
      underlying mitochondrial cytopathies can serve as diagnostic "red-flags." Here,
      the typical and atypical presentations of mitochondrial disease in the nervous
      system are reviewed, focusing on "red flag" neurological symptoms as well as
      associated symptoms that can occur in, but are not specific to, mitochondrial
      disease. The multitudes of mitochondrial syndromes are not reviewed in-depth,
      though a select few are discussed in some detail.

PMID- 20818724
TI  - Historical perspective on mitochondrial medicine.
AB  - In this review, we trace the origins and follow the development of mitochondrial
      medicine from the premolecular era (1962-1988) based on clinical clues, muscle
      morphology, and biochemistry into the molecular era that started in 1988 and is
      still advancing at a brisk pace. We have tried to stress conceptual advances,
      such as endosymbiosis, uniparental inheritance, intergenomic signaling and its
      defects, and mitochondrial dynamics. We hope that this historical review also
      provides an update on mitochondrial medicine, although we fully realize that the
      speed of progress in this area makes any such endeavor akin to writing on water.

PMID- 20818727
TI  - The use of neuroimaging in the diagnosis of mitochondrial disease.
AB  - Mutations in nuclear and mitochondrial DNA impacting mitochondrial function
      result in disease manifestations ranging from early death to abnormalities in all
      major organ systems and to symptoms that can be largely confined to muscle
      fatigue. The definitive diagnosis of a mitochondrial disorder can be difficult to
      establish. When the constellation of symptoms is suggestive of mitochondrial
      disease, neuroimaging features may be diagnostic and suggestive, can help direct
      further workup, and can help to further characterize the underlying brain
      abnormalities. Magnetic resonance imaging changes may be nonspecific, such as
      atrophy (both general and involving specific structures, such as cerebellum),
      more suggestive of particular disorders such as focal and often bilateral lesions
      confined to deep brain nuclei, or clearly characteristic of a given disorder such
      as stroke-like lesions that do not respect vascular boundaries in mitochondrial
      myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS). White
      matter hyperintensities with or without associated gray matter involvement may
      also be observed. Across patients and discrete disease subtypes (e.g., MELAS,
      Leigh syndrome, etc.), patterns of these features are helpful for diagnosis.
      However, it is also true that marked variability in expression occurs in all
      mitochondrial disease subtypes, illustrative of the complexity of the disease
      process. The present review summarizes the role of neuroimaging in the diagnosis
      and characterization of patients with suspected mitochondrial disease.

PMID- 20818728
TI  - The role of mitochondrial dysfunction in psychiatric disease.
AB  - Mitochondrial respiratory chain disorders are a group of genetically and
      clinically heterogeneous disorders caused by the biochemical complexity of
      mitochondrial respiration and the fact that two genomes, one mitochondrial and
      one nuclear, encode the components of the respiratory chain. These disorders can
      manifest at birth or present later in life. They result, at least in part, in
      defective production of ATP. Typically, mitochondrial disorders affect tissues
      with high energetic demands such as skeletal muscle, cardiac muscle, and the
      central nervous system. Neurological dysfunction is the most frequent clinical
      presentation of these disorders. The central nervous system is highly dependent
      on oxidative metabolism, and particular mitochondrial disorders are accompanied
      by focal brain necrosis (Leigh disease), dementia, or static encephalopathy.
      Furthermore, many children with mitochondrial encephalomyopathies present with
      more subtle and indolent signs including focal cognitive deficits of memory,
      perception, and language. Some subjects with mitochondrial disorders may also
      exhibit nonverbal cognitive impairment, compromised visuospatial abilities, and
      short-term memory deficits associated with working memory that likely reflect
      defects in synaptic plasticity. Psychiatric features are found within the
      clinical spectrum of mitochondrial syndromes. It is increasingly recognized that
      mitochondrial dysfunction may be associated with neuropsychiatric abnormalities
      such as dementia, major depression, and bipolar disorder. Furthermore, several
      lines of evidence suggest that there is involvement of mitochondrial dysfunction
      in schizophrenia, including documented alterations in brain energy metabolism,
      electron transport chain activity, and expression of genes involved in
      mitochondrial function. The purpose of this review article is to summarize the
      psychiatric features observed in mitochondrial cytopathies and discuss possible
      mechanisms of dysfunctional cellular energy metabolism that underlie the
      pathophysiology of major subsets of psychiatric disorders.

PMID- 20818729
TI  - Autism and mitochondrial disease.
AB  - Autism spectrum disorder (ASD) as defined by the revised Diagnostic and
      Statistical Manual of Mental Disorders: DSM IVTR criteria (American Psychiatric
      Association [2000] Washington, DC: American Psychiatric Publishing) as impairment
      before the age of 3 in language development and socialization with the
      development of repetitive behaviors, appears to be increased in incidence and
      prevalence. Similarly, mitochondrial disorders are increasingly recognized.
      Although overlap between these disorders is to be expected, accumulating
      clinical, genetic, and biochemical evidence suggests that mitochondrial
      dysfunction in ASD is more commonly seen than expected. Some patients with ASD
      phenotypes clearly have genetic-based primary mitochondrial disease. This review
      will examine the data linking autism and mitochondria.

PMID- 20818730
TI  - Molecular genetics of mitochondrial disorders.
AB  - Mitochondrial respiratory chain (RC) disorders (RCDs) are a group of genetically
      and clinically heterogeneous diseases because of the fact that protein components
      of the RC are encoded by both mitochondrial and nuclear genomes and are essential
      in all cells. In addition, the biogenesis, structure, and function of
      mitochondria, including DNA replication, transcription, and translation, all
      require nuclear-encoded genes. In this review, primary molecular defects in the
      mitochondrial genome and major classes of nuclear genes causing mitochondrial
      RCDs, including genes underlying mitochondrial DNA (mtDNA) depletion syndrome, as
      well as genes encoding RC subunits, complex assembly genes, and translation
      factors, are described. Diagnostic methodologies used to detect common point
      mutations, large deletions, and unknown point mutations in the mtDNA and to
      quantify mutation heteroplasmy are also discussed. Finally, the selection of
      nuclear genes for gold standard sequence analysis, application of novel
      technologies including oligonucleotide array comparative genomic hybridization,
      and massive parallel sequencing of target genes are reviewed.

PMID- 20818731
TI  - Polymerase gamma disease through the ages.
AB  - The most common group of mitochondrial disease is due to mutations within the
      mitochondrial DNA polymerase, polymerase gamma 1 (POLG). This gene product is
      responsible for replication and repair of the small mitochondrial DNA genome. The
      structure-function relationship of this gene product produces a wide variety of
      diseases that at times, seems to defy the common perceptions of genetics. The
      unique features of mitochondrial physiology are in part responsible, but POLG
      structure and function add to the conundrum of how one gene product can
      demonstrate autosomal recessive and autosomal dominant transmission, while also
      being responsible for pharmacogenetic disease, and exhibiting strong gene
      environment interactions. The wide spectrum of clinical manifestations of POLG
      disease can arise from infancy to old age. The modulation of clinical findings
      relate in part to the molecular architecture of the POLG protein. POLG has three
      distinct molecular domains: exonuclease, linker, and polymerase domains. Most of
      the mutations leading to dominant forms of POLG disease are located in the
      Polymerase domain. Mutations leading to recessive inheritance are distributed in
      all three domains of the gene. Environmental factors like valproic acid and
      infection can unmask POLG disease, causing it to occur earlier in life than when
      not exposed to these factors. Other drugs like nucleoside reverse transcriptase
      inhibitors can produce genotype-specific POLG pharmacogenetic disease. Our
      current state of POLG understanding cannot account for many features of POLG
      disease. There is no answer for why the same mutation can give rise to varying
      diseases, disease severity, and age of onset. We introduce the term Ecogenetics
      in the context these features of POLG disease, to emphasize the important
      interactions between genes and environment in determining the expression of
      mitochondrial disease. In this article, we identify some of the key features that
      will help the reader understand POLG pathophysiology. When possible, we also
      identify genotype-phenotype relationships, give clues for diagnosis, and
      summarize the major clinical phenotypes in the spectrum of POLG disease
      presenting from birth to old age.

PMID- 20818732
TI  - Complex I disorders: causes, mechanisms, and development of treatment strategies
      at the cellular level.
AB  - Mitochondrial oxidative phosphorylation (OXPHOS) represents the final step in the
      conversion of nutrients into cellular energy. Genetic defects in the OXPHOS
      system have an incidence between 1:5,000 and 1:10,000 live births. Inherited
      isolated deficiency of the first complex (CI) of this system, a multisubunit
      assembly of 45 different proteins, occurs most frequently and originates from
      mutations in either the nuclear DNA, encoding 38 structural subunits and several
      assembly factors, or the mitochondrial DNA, encoding 7 structural subunits. The
      deficiency is associated with devastating multisystemic disorders, often
      affecting the brain, with onset in early childhood. There are currently no
      rational treatment strategies. Here, we present an overview of the genetic
      origins and cellular consequences of this deficiency and discuss how these
      insights might aid future development of treatment strategies.

PMID- 20818733
TI  - Coenzyme Q and mitochondrial disease.
AB  - Coenzyme Q(10) (CoQ(10)) is an essential electron carrier in the mitochondrial
      respiratory chain and an important antioxidant. Deficiency of CoQ(10) is a
      clinically and molecularly heterogeneous syndrome, which, to date, has been found
      to be autosomal recessive in inheritance and generally responsive to CoQ(10)
      supplementation. CoQ(10) deficiency has been associated with five major clinical
      phenotypes: (1) encephalomyopathy, (2) severe infantile multisystemic disease,
      (3) cerebellar ataxia, (4) isolated myopathy, and (5) nephrotic syndrome. In a
      few patients, pathogenic mutations have been identified in genes involved in the
      biosynthesis of CoQ(10) (primary CoQ(10) deficiencies) or in genes not directly
      related to CoQ(10) biosynthesis (secondary CoQ(10) deficiencies). Respiratory
      chain defects, ROS production, and apoptosis contribute to the pathogenesis of
      primary CoQ(10) deficiencies. In vitro and in vivo studies are necessary to
      further understand the pathogenesis of the disease and to develop more effective
      therapies.

PMID- 20818734
TI  - Pharmacologic effects on mitochondrial function.
AB  - The vast majority of energy necessary for cellular function is produced in
      mitochondria. Free-radical production and apoptosis are other critical
      mitochondrial functions. The complex structure, electrochemical properties of the
      inner mitochondrial membrane (IMM), and genetic control from both mitochondrial
      DNA (mtDNA) and nuclear DNA (nDNA) are some of the unique features that explain
      why the mitochondria are vulnerable to environmental injury. Because of
      similarity to bacterial translational machinery, mtDNA translation is likewise
      vulnerable to inhibition by some antibiotics. The mechanism of mtDNA replication,
      which is required for normal mitochondrial maintenance and duplication, is
      inhibited by a relatively new class of drugs used to treat AIDS. The
      electrochemical gradient maintained by the IMM is vulnerable to many drugs that
      are weak organic acids at physiological pH, resulting in excessive free-radical
      generation and uncoupling of oxidative phosphorylation. Many of these drugs can
      cause clinical injury in otherwise healthy people, but there are also examples
      where particular gene mutations may predispose to increased drug toxicity. The
      spectrum of drug-induced mitochondrial dysfunction extends across many drug
      classes. It is hoped that preclinical pharmacogenetic and functional studies of
      mitochondrial toxicity, along with personalized genomic medicine, will improve
      both our understanding of mitochondrial drug toxicity and patient safety.

PMID- 20818736
TI  - Emerging therapeutic approaches to mitochondrial diseases.
AB  - Mitochondrial diseases are very heterogeneous and can affect different tissues
      and organs. Moreover, they can be caused by genetic defects in either nuclear or
      mitochondrial DNA as well as by environmental factors. All of these factors have
      made the development of therapies difficult. In this review article, we will
      discuss emerging approaches to the therapy of mitochondrial disorders, some of
      which are targeted to specific conditions whereas others may be applicable to a
      more diverse group of patients.

PMID- 20818737
TI  - Race and receipt of liver transplantation: location matters.

PMID- 20818738
TI  - Beyond graft survival and into the classroom: should school performance become a
      new posttransplant outcome measure?

PMID- 20818735
TI  - Bacteria, yeast, worms, and flies: exploiting simple model organisms to
      investigate human mitochondrial diseases.
AB  - The extensive conservation of mitochondrial structure, composition, and function
      across evolution offers a unique opportunity to expand our understanding of human
      mitochondrial biology and disease. By investigating the biology of much simpler
      model organisms, it is often possible to answer questions that are unreachable at
      the clinical level. Here, we review the relative utility of four different model
      organisms, namely the bacterium Escherichia coli, the yeast Saccharomyces
      cerevisiae, the nematode Caenorhabditis elegans, and the fruit fly Drosophila
      melanogaster, in studying the role of mitochondrial proteins relevant to human
      disease. E. coli are single cell, prokaryotic bacteria that have proven to be a
      useful model system in which to investigate mitochondrial respiratory chain
      protein structure and function. S. cerevisiae is a single-celled eukaryote that
      can grow equally well by mitochondrial-dependent respiration or by ethanol
      fermentation, a property that has proven to be a veritable boon for investigating
      mitochondrial functionality. C. elegans is a multicellular, microscopic worm that
      is organized into five major tissues and has proven to be a robust model animal
      for in vitro and in vivo studies of primary respiratory chain dysfunction and its
      potential therapies in humans. Studied for over a century, D. melanogaster is a
      classic metazoan model system offering an abundance of genetic tools and reagents
      that facilitates investigations of mitochondrial biology using both forward and
      reverse genetics. The respective strengths and limitations of each species
      relative to mitochondrial studies are explored. In addition, an overview is
      provided of major discoveries made in mitochondrial biology in each of these four
      model systems.

PMID- 20818739
TI  - Liver ischemia/reperfusion injury: processes in inflammatory networks--a review.
AB  - Liver ischemia/reperfusion (IR) injury is typified by an inflammatory response.
      Understanding the cellular and molecular events underpinning this inflammation is
      fundamental to developing therapeutic strategies. Great strides have been made in
      this respect recently. Liver IR involves a complex web of interactions between
      the various cellular and humoral contributors to the inflammatory response.
      Kupffer cells, CD4+ lymphocytes, neutrophils, and hepatocytes are central
      cellular players. Various cytokines, chemokines, and complement proteins form the
      communication system between the cellular components. The contribution of the
      danger-associated molecular patterns and pattern recognition receptors to the
      pathophysiology of liver IR injury are slowly being elucidated. Our knowledge on
      the role of mitochondria in generating reactive oxygen and nitrogen species, in
      contributing to ionic disturbances, and in initiating the mitochondrial
      permeability transition with subsequent cellular death in liver IR injury is
      continuously being expanded. Here, we discuss recent findings pertaining to the
      aforementioned factors of liver IR, and we highlight areas with gaps in our
      knowledge, necessitating further research.

PMID- 20818740
TI  - Racial and ethnic disparities in access to liver transplantation.
AB  - Access to liver transplantation is reportedly inequitable for racial/ethnic
      minorities, but inadequate adjustments for geography and disease progression
      preclude any meaningful conclusions. We aimed to evaluate the association between
      candidate race/ethnicity and liver transplant rates after thorough adjustments
      for these factors and to determine how uniform racial/ethnic disparities were
      across Model for End-Stage Liver Disease (MELD) scores. Chronic end-stage liver
      disease candidates initially wait-listed between February 28, 2002 and February
      27, 2007 were identified from Scientific Registry for Transplant Recipients data.
      The primary outcome was deceased donor liver transplantation (DDLT); the primary
      exposure covariate was race/ethnicity (white, African American, Hispanic, Asian,
      and other). Cox regression was used to estimate the covariate-adjusted DDLT rates
      by race/ethnicity, which were stratified by the donation service area and MELD
      score. With averaging across all MELD scores, African Americans, Asians, and
      others had similar adjusted DDLT rates in comparison with whites. However,
      Hispanics had an 8% lower DDLT rate versus whites [hazard ratio (HR) = 0.92, P =
      0.011]. The disparity among Hispanics was concentrated among patients with MELD
      scores < 20, with HR = 0.84 (P = 0.021) for MELD scores of 6 to 14 and HR = 0.85
      (P = 0.009) for MELD scores of 15 to 19. Asians with MELD scores < 15 had a 24%
      higher DDLT rate with respect to whites (HR = 1.24, P = 0.024). However, Asians
      with MELD scores of 30 to 40 had a 46% lower DDLT rate (HR = 0.54, P = 0.004). In
      conclusion, although African Americans did not have significantly different DDLT
      rates in comparison with similar white candidates, race/ethnicity-based
      disparities were prominent among subgroups of Hispanic and Asian candidates. By
      precluding the survival benefit of liver transplantation, this inequity may lead
      to excess mortality for minority candidates.

PMID- 20818741
TI  - School outcomes in children registered in the studies for pediatric liver
      transplant (SPLIT) consortium.
AB  - School performance is an important aspect of functional outcomes for pediatric
      liver transplant (LT) recipients. This longitudinal analysis conducted through
      the Studies of Pediatric Liver Transplantation (SPLIT) research consortium
      examines several indicators of school function in these patients. A total of 39
      centers participated in data collection using a semistructured questionnaire
      designed specifically for this study. The survey queried school attendance,
      performance and educational outcomes including the need for special educational
      services. Participants included 823 of 1133 (73%) eligible patients, mean age
      11.34 +/- 3.84 years, 53% female, median age at LT 4.6 (range 0.05-17.8) years,
      and mean interval from transplant was 5.42 +/- 2.79. Overall, 34% of patients
      were receiving special educational services and 20% had repeated a grade, with
      older participants more likely to have been held back (P = 0.0007). Missing more
      than 10 days of school per year was reported by one-third of the group, with this
      level of absence being more common in older participants (P = 0.0024) and
      children with shorter intervals from LT (P < 0.0001). Multivariate analysis
      revealed the following factors were associated with the need for special
      educational services; type of immunosuppression at 6 months post-LT, cyclosporine
      A (odds ratio [OR] = 1.8, confidence interval [CI] = 1.1-3.1), or other (OR =
      4.9, 95% CI = 1.4-17.6) versus tacrolimus, symptomatic cytomegalovirus infection
      within 6 months of liver transplantation (OR = 3.1, CI = 1.6-6.1), and
      pretransplant special educational services (OR = 22.5, CI = 8.6-58.4).

PMID- 20818742
TI  - Recurrent liver failure in a 25-year-old female.
AB  - Acute liver failure (ALF) is defined as severe and sudden liver dysfunction
      leading to coagulopathy and encephalopathy in a previously healthy person without
      preexisting liver disease. Almost half of adult cases of ALF are due to
      acetaminophen toxicity, with 21% labeled indeterminate or other. We present a
      patient with a second episode of ALF, both episodes being initiated by catabolic
      stress. Elevated aminotransferases, jaundice, an elevated international
      normalized ratio, and confusion were typical of idiopathic ALF, and a low serum
      ceruloplasmin level initially led to a misdiagnosis of acute Wilson disease.
      Citrullinemia type I, a urea cycle defect caused by a deficiency of
      argininosuccinate synthetase, was diagnosed on the basis of plasma amino acids
      and was confirmed by molecular testing. Urea cycle defects are not generally
      considered causes of ALF in adults and are described rarely in children beyond
      the neonatal period. Our case illustrates the importance of screening patients
      with idiopathic ALF for a metabolic disorder. A prompt diagnosis and timely
      treatment enabled her to recover fully without the need for liver
      transplantation.

PMID- 20818743
TI  - Extra-anatomical hepatic artery reconstruction in living donor liver
      transplantation: can this procedure save hepatic grafts?
AB  - Graft hepatic arteries (HAs) are usually reconstructed with a recipient HA branch
      (anatomical HA reconstruction) in living donor liver transplantation (LDLT).
      Surgeons often encounter difficulties in reconstructing HAs, particularly when a
      recipient artery other than an HA branch must be used; this is known as extra
      anatomical HA reconstruction. The outcomes of LDLT recipients with extra
      anatomical HA reconstruction were retrospectively reviewed. Between October 1996
      and October 2009, we performed primary LDLT 335 times, re-LDLT 8 times, and HA re
      reconstruction 5 times for patients with HA complications. Thirty-three extra
      anatomical HA reconstructions were performed in 22 patients with primary LDLT
      (6.6%), 4 patients with re-LDLT (50%), and 4 patients with HA re-reconstructions
      for HA complications (80%). In extra-anatomical HA reconstructions, we used 12
      right gastroepiploic arteries, 6 right gastric arteries, 5 gastroduodenal
      arteries, 2 left gastric arteries, 2 splenic arteries, 2 cystic arteries, and 4
      interposition grafts as recipient inflow arteries. Only 1 HA-related
      complication, the formation of an aneurysm, occurred after extra-anatomical HA
      reconstruction. The overall graft and patient survival probabilities after
      primary LDLT with extra-anatomical HA reconstruction were comparable to those
      after LDLT with anatomical HA reconstruction, although approximately half of the
      patients with extra-anatomical HA reconstruction suffered anastomotic biliary
      strictures. Therefore, extra-anatomical HA reconstruction can be safely performed
      through the proper selection of recipient arteries and the use of interposition
      grafts. These procedures can save hepatic grafts, even when recipient HAs cannot
      be used as inflow arteries.

PMID- 20818744
TI  - Three-dimensional computed tomography scan analysis of hepatic vasculatures in
      the donor liver for living donor liver transplantation.
AB  - Because hepatic vasculatures exhibit variations, a preoperative evaluation of the
      vascular anatomy and an estimation of the volume of the liver graft are essential
      for successful adult living donor liver transplantation. Using 3-dimensional (3D)
      computed tomography (CT), we analyzed the volumetric and anatomical relationship
      of the hepatic vasculatures of liver grafts. The livers of 223 potential donors
      were analyzed by 3D CT. Volumetric analysis was performed for each hepatic vein
      and its tributaries. The anatomy of the portal vein and hepatic artery was
      assessed along with the biliary system via intraoperative cholangiography in 110
      recipients. On the basis of the anatomical presentation of the inferior right
      hepatic vein (IRHV), the hepatic veins were classified as follows: in type I, the
      IRHV was absent; in type II, the IRHV was smaller than the right hepatic vein
      (RHV); and in type III, the IRHV was greater than or equal to the RHV in size.
      The drainage volume of the middle hepatic vein (MHV) and especially its
      tributaries in the right lobe increased with the size of the IRHV (P < 0.001). In
      type III hepatic veins with a large IRHV (17% of the donors), the MHV tributaries
      had the largest drainage volume in the right lobe (41.2% +/- 11.8%). Furthermore,
      type III hepatic veins typically exhibited biliary variations in 75% of the
      donors. No correlation was observed between variations in the hepatic artery and
      portal vein. In conclusion, a right lobe graft with a large IRHV is accompanied
      by a large drainage volume via the MHV and by bile duct variations in 17% of
      livers. Therefore, anatomical and volumetric analysis is important for
      preoperative evaluations.

PMID- 20818745
TI  - Tailored telescopic reconstruction of the bile duct in living donor liver
      transplantation.
AB  - Duct-to-duct reconstruction (DDR) of the bile duct has recently become the
      preferred choice in living donor liver transplantation (LDLT), but biliary
      complications still remain the most common cause of morbidity. We introduce our
      new technique of tailored telescopic reconstruction (TTR) of the bile duct for
      reducing bile duct complications in LDLT: the hilar plate covering the right and
      left hepatic ducts is bisected lengthwise through the right or left hepatic duct
      opening to make a funnel-shaped top, into which the donor hepatic duct is
      telescoped to match the recipient bile duct in size, and DDR is performed in the
      inner tissue of good vascular integrity of the recipient bile duct without
      redundancy. Forty-five consecutive LDLT procedures from January to August 2008
      were analyzed through a comparison of 23 conventional duct-to-duct
      reconstructions (cDDRs) and 22 TTRs in bile duct anastomoses. At a mean follow-up
      of 19.5 months, the rates of overall biliary complications, leakage, and
      strictures were 43.5%, 26.1%, and 34.8%, respectively, for cDDR and 9.1%, 0%, and
      9.1%, respectively, for TTR (P < 0.05 for each). In conclusion, TTR of the bile
      duct results in excellent outcomes with respect to minimization of biliary
      complications; thus, TTR can be recommended as a preferred method for biliary
      reconstruction in LDLT.

PMID- 20818746
TI  - Stable overexpression of pregnane X receptor in HepG2 cells increases its
      potential for bioartificial liver application.
AB  - To bridge patients with acute liver failure to transplantation or liver
      regeneration, a bioartificial liver (BAL) is urgently needed. A BAL consists of
      an extracorporeal bioreactor loaded with a bioactive mass that would preferably
      be of human origin and display high hepatic functionality, including
      detoxification. The human hepatoma cell line HepG2 exhibits many hepatic
      functions, but its detoxification function is low. In this study, we investigated
      whether stable overexpression of pregnane X receptor (PXR), a master regulator of
      diverse detoxification functions in the liver [eg, cytochrome P450 3A (CYP3A)
      activity], would increase the potential of HepG2 for BAL application. Stable
      overexpression was achieved by lentiviral expression of the human PXR gene, which
      yielded cell line cBAL119. In monolayer cultures of cBAL119 cells, PXR transcript
      levels increased 29-fold versus HepG2 cells. Upon activation of PXR by
      rifampicin, the messenger RNA levels of CYP3A4, CYP3A5, and CYP3A7 increased 49-
      to 213-fold versus HepG2 cells. According to reporter gene assays with different
      inducers, the highest increase in CYP3A4 promoter activity (131-fold) was
      observed upon induction with rifampicin. Inside BALs, the proliferation rates, as
      measured by the DNA content, were comparable between the 2 cell lines. The rate
      of testosterone 6beta-hydroxylation, a measure of CYP3A function inside BALs,
      increased 4-fold in cBAL119 BALs versus HepG2 BALs. Other functions, such as
      apolipoprotein A1 synthesis, urea synthesis, glucose consumption, and lactate
      production, remained unchanged or increased. Thus, stable PXR overexpression
      markedly increases the potential of HepG2 for BAL application.

PMID- 20818747
TI  - Hepatic differentiation of liver-derived progenitor cells and their
      characterization by microRNA analysis.
AB  - We recently reported the isolation and characterization of a novel population of
      progenitor cells called liver-derived progenitor cells (LDPCs), which could
      differentiate into functional hepatocytes in vitro. However, our original studies
      resulted in relatively low and variable hepatic differentiation efficiency
      without validation of in vivo potential of LDPCs. Here, we report an efficient
      and robust hepatic differentiation of LDPCs under well-defined culture conditions
      and in vivo differentiation of LDPCs to mature hepatocytes. In addition to
      morphological studies, we performed reverse-transcription polymerase chain
      reaction (RT-PCR) and microRNA analyses of the in vitro hepatic differentiation
      of LDPCs to substantiate the efficiency of the differentiation process. The
      histological studies on the differentiated LDPCs showed that more than 50% of the
      cells were positive for albumin, cytokeratin 18, and hepatocyte nuclear factor 1
      alpha and contained glycogen particles, all consistent with differentiation to
      functional hepatocytes. We also demonstrated by RT-PCR that upon differentiation,
      they expressed several markers found in mature hepatocytes and the microRNA
      profile of LDPCs became similar to the profile of fresh hepatocytes, confirming
      our morphological findings. Finally, the transplantation of LDPCs in a dipeptidyl
      peptidase IV-deficient (DPPIV(-/-)) rat model showed that LDPCs were able to
      engraft and form mature hepatocytes in the livers of the DPPIV(-/-) rats. In
      summary, LDPCs are a unique population of liver progenitor cells capable of
      hepatic differentiation both in vitro and in vivo, which makes them a potentially
      valuable resource for important applications such as pharmacological studies and
      cell therapies for a variety of liver disorders.

PMID- 20818748
TI  - Improved rat steatotic and nonsteatotic liver preservation by the addition of
      epidermal growth factor and insulin-like growth factor-I to University of
      Wisconsin solution.
AB  - This study examined the effects of epidermal growth factor (EGF) and insulin-like
      growth factor-I (IGF-I) supplementation to University of Wisconsin solution (UW)
      in steatotic and nonsteatotic livers during cold storage. Hepatic injury and
      function were evaluated in livers preserved for 24 hours at 4 degrees C in UW and
      in UW with EGF and IGF-I (separately or in combination) and then perfused ex vivo
      for 2 hours at 37 degrees C. AKT was inhibited pharmacologically. In addition,
      hepatic injury and survival were evaluated in recipients who underwent
      transplantation with steatotic and nonsteatotic livers preserved for 6 hours in
      UW and UW with EGF and IGF-I (separately or in combination). The results, based
      on isolated perfused liver, indicated that the addition of EGF and IGF-I
      (separately or in combination) to UW reduced hepatic injury and improved function
      in both liver types. A combination of EGF and IGF-I resulted in hepatic injury
      and function parameters in both liver types similar to those obtained by EGF and
      IGF-I separately. EGF increased IGF-I, and both additives up-regulated AKT in
      both liver types. This was associated with glycogen synthase kinase-3beta
      (GSK3(beta)) inhibition in nonsteatotic livers and PPAR gamma overexpression in
      steatotic livers. When AKT was inhibited, the effects of EGF and IGF-I on
      GSK3(beta), PPAR gamma, hepatic injury and function disappeared. The benefits of
      EGF and IGF-I as additives in UW solution were also clearly seen in the liver
      transplantation model, because the presence of EGF and IGF-I (separately or in
      combination) in UW solution reduced hepatic injury and improved survival in
      recipients who underwent transplantation with steatotic and nonsteatotic liver
      grafts. In conclusion, EGF and IGF-I may constitute new additives to UW solution
      in steatotic and nonsteatotic liver preservation, whereas a combination of both
      seems unnecessary.

PMID- 20818749
TI  - Blockade of Janus kinase 2 signaling ameliorates mouse liver damage due to
      ischemia and reperfusion.

PMID- 20818753
TI  - In pursuit of a competitive target: total synthesis of the antibiotic kendomycin.
AB  - Kendomycin is a novel polyketide having a unique quinone methide ansa structure
      and an impressive biological profile. Herein we provide a chronological overview
      of the synthetic work towards the title compound. Thus far, over a period of
      about eight years, eight groups worldwide have published on their synthetic
      efforts resulting in five total syntheses, one formal synthesis, and a number of
      fragment syntheses. Most approaches roughly mimic the biogenetic pathway,
      starting with an aromatic polyphenol subunit to which a polyketide chain is
      attached. Subsequent key steps include macrocyclization and the formation of the
      densely substituted tetrahydropyran ring, and then a late-stage oxidation and
      lactol formation.

PMID- 20818754
TI  - Bonding in the heavy analogue of hydrogen cyanide: the curious case of bridged
      HPSi.

PMID- 20818755
TI  - A graphene-based platform for the assay of duplex-DNA unwinding by helicase.

PMID- 20818756
TI  - A fragment-based in situ combinatorial approach to identify high-affinity ligands
      for unknown binding sites.

PMID- 20818757
TI  - Polyacrylate dendrimer nanoparticles: a self-adjuvanting vaccine delivery system.

PMID- 20818758
TI  - Glycosidase inhibition with fullerene iminosugar balls: a dramatic multivalent
      effect.

PMID- 20818759
TI  - Enantioselective synthesis of trifluoromethyl-substituted 2-isoxazolines:
      asymmetric hydroxylamine/enone cascade reaction.

PMID- 20818760
TI  - Rhodium-catalyzed asymmetric conjugate addition of organoboronic acids to
      nitroalkenes using chiral bicyclo[3.3.0] diene ligands.

PMID- 20818761
TI  - Cleavage of C-S and O-H bonds by platinum(0) complexes to give five-membered 1,2
      oxaplatinacycles.

PMID- 20818765
TI  - Thinner, smaller, faster: IR techniques to probe the functionality of biological
      and biomimetic systems.
AB  - New techniques in vibrational spectroscopy are promising for the study of
      biological samples as they provide exquisite spatial and/or temporal resolution
      with the benefit of minimal perturbation of the system during observation. In
      this Minireview we showcase the power of modern infrared techniques when applied
      to biological and biomimetic systems. Examples will be presented on how
      conformational changes in peptides can be traced with femtosecond resolution and
      nanometer sensitivity by 2D IR spectroscopy, and how surface-enhanced infrared
      difference absorption spectroscopy can be used to monitor the effect of the
      membrane potential on a single proton-transfer step in an integral membrane
      protein. Vibrational spectra of monolayers of molecules at basically any
      interface can be recorded with sum-frequency generation, which is strictly
      surface-sensitive. Chemical images are recorded by applying scanning near-field
      infrared microscopy at lateral resolutions better than 50 nm.

PMID- 20818766
TI  - Highly selective metalations of pyridines and related heterocycles using new
      frustrated Lewis pairs or tmp-zinc and tmp-magnesium bases with BF3.OEt2.

PMID- 20818767
TI  - Chiral ammonium betaines as ionic nucleophilic catalysts.

PMID- 20818771
TI  - Enantioselective palladium-catalyzed direct alkylation and olefination reaction
      of simple arenes.

PMID- 20818772
TI  - Picosecond time-resolved X-ray emission spectroscopy: ultrafast spin-state
      determination in an iron complex.

PMID- 20818773
TI  - Controlled reducibility of a metal-organic framework with coordinatively
      unsaturated sites for preferential gas sorption.

PMID- 20818775
TI  - Self-assembling peptide amphiphile promotes plasticity of serotonergic fibers
      following spinal cord injury.
AB  - Injection into the injured spinal cord of peptide amphiphile (PA) molecules that
      self-assemble and display the laminin epitope IKVAV at high density improved
      functional recovery after spinal cord injury (SCI) in two different species, rat
      and mouse, and in two different injury models, contusion and compression. The
      improvement required the IKVAV epitope and was not observed with the injection of
      an amphiphile displaying a nonbioactive sequence. To explore the mechanisms
      underlying these improvements, the number of serotonergic fibers in the lesioned
      spinal cord was compared in animals receiving the IKVAV-PA, a nonbioactive PA (PA
      control), or sham injection. Serotonergic fibers were distributed equally in all
      three groups rostral to the injury but showed a significantly higher density
      caudal to the injury site in the IKVAV PA-injected group. Furthermore, this
      difference was not present in the subacute phase following injury but appeared in
      the chronically injured cord. The IKVAV PA-injected groups also trended higher
      both in the total number neurons adjacent to the lesion and in the number of long
      propriospinal tract connections from the thoracic to the lumbar cord. IKVAV PA
      injection did not alter myelin thickness, total axon number caudal to the lesion,
      axon size distribution, or total axon area. Serotonin can promote stepping even
      in complete transection models, so the improved function produced by the IKVAV PA
      treatment may reflect the increased serotonergic innervation caudal to the lesion
      in addition to the previously demonstrated regeneration of motor and sensory
      axons through the lesion.

PMID- 20818776
TI  - Human neural stem cells genetically modified to overexpress brain-derived
      neurotrophic factor promote functional recovery and neuroprotection in a mouse
      stroke model.
AB  - Intracerebral hemorrhage (ICH) is a lethal stroke type; mortality approaches 50%,
      and current medical therapy against ICH shows only limited effectiveness, so an
      alternative approach is required, such as stem cell-based cell therapy.
      Previously we have shown that intravenously transplanted human neural stem cells
      (NSCs) selectively migrate to the brain and promote functional recovery in rat
      ICH model, and others have shown that intracerebral infusion of brain-derived
      neurotrophic factor (BDNF) results in improved structural and functional outcome
      from cerebral ischemia. We postulated that human NSCs overexpressing BDNF
      transplanted into cerebral cortex overlying ICH lesion could provide improved
      survival of grafted NSCs and increased angiogenesis and behavioral recovery in
      mouse ICH model. ICH was induced in adult mice by injection of bacterial
      collagenase into striatum. The HB1.F3.BDNF (F3.BDNF) human NSC line produces
      sixfold higher amounts of BDNFF over the parental F3 cell line in vitro, induces
      behavioral improvement, and produces a threefold increase in cell survival at 2
      weeks and 8 weeks posttransplantation. Brain transplantation of human NSCs
      overexpressing BDNF provided differentiation and survival of grafted human NSCs
      and renewed angiogenesis of host brain and functional recovery of ICH animals.
      These results indicate that the F3.BDNF human NSCs should be of great value as a
      cellular source for experimental studies involving cellular therapy for human
      neurological disorders, including ICH.

PMID- 20818777
TI  - A capacitively coupled temperature-jump arrangement for high-resolution
      biomolecular NMR.
AB  - A simple design for performing rapid temperature jumps within a high-resolution
      nuclear magnetic resonance (NMR) setting is presented and exemplified. The design
      is based on mounting, around a conventional NMR glass tube, an inductive
      radiofrequency (RF) irradiation coil that is suitably tuned by a resonant circuit
      and is driven by one of the NMR's console high-power RF amplifiers. The electric
      fields generated by this coil's thin metal strips can lead to a fast and
      efficient heating of the sample, amounting to temperature jumps of ~ 20  degrees
      C in well within a second-particularly in the presence of lossy dielectric media
      like those provided by physiological buffers. Moreover, when wound around a 4-mm
      NMR tube, the resulting device fits a conventional 5-mm inverse probe and is
      wholly compatible with the field homogeneities and sensitivities expected for
      high-resolution biomolecular NMR conditions. The performance characteristics of
      this new system were tested using saline solutions, as well as on a lyotropic
      liquid crystal capable of undergoing nematic -> isotropic transitions in the
      neighborhood of ambient temperature. These settings were then incorporated into
      the performance of a new kind of single-scan 2D NMR spectroscopy acquisition,
      correlating the anisotropic and isotropic patterns elicited by solutes dissolved
      in such liquid-crystalline systems, before and after a sudden temperature jump
      occurring during an intervening mixing period.

PMID- 20818778
TI  - NerveCenter: Sumatriptan's evolution from brand drug to best buy of 2010.

PMID- 20818779
TI  - NerveCenter: FDA requirements for generic drug applications.

PMID- 20818781
TI  - Fred Plum (1924-2010) and the founding of the Annals of Neurology.

PMID- 20818782
TI  - NerveCenter: Translational research and the shifting landscape for physician
      scientists.

PMID- 20818783
TI  - NerveCenter: At a glance: NIH programs supporting translational research in
      neurological disease.

PMID- 20818784
TI  - Progressive multifocal leukoencephalopathy: can we reduce risk in patients
      receiving biological immunomodulatory therapies?

PMID- 20818785
TI  - Biomarkers of Alzheimer's disease and exercise: one step closer to prevention.

PMID- 20818786
TI  - Amyloid imaging: coming to a PET scanner near you.

PMID- 20818787
TI  - Refining neuroprotection strategies in the era of therapeutic hypothermia.

PMID- 20818788
TI  - Neurological disorders in complex humanitarian emergencies and natural disasters.
AB  - Complex humanitarian emergencies include the relatively acute, severe, and
      overwhelming health consequences of armed conflict, food scarcity, mass
      displacement, and political strife. Neurological manifestations of complex
      humanitarian emergencies are important and underappreciated consequences of
      emergencies in populations worldwide. This review critically assesses the
      existing knowledge of the range of neurological disorders that accompany complex
      humanitarian emergencies and natural disasters in both the acute phase of crisis
      and the "long shadow" that follows.

PMID- 20818789
TI  - Exercise and Alzheimer's disease biomarkers in cognitively normal older adults.
AB  - OBJECTIVE: In addition to the increasingly recognized role of physical exercise
      in maintaining cognition, exercise may influence Alzheimer's disease (AD)
      pathology, as transgenic mouse studies show lowered levels of AD pathology in
      exercise groups. The objective of this study was to elucidate the association
      between exercise and AD pathology in humans using Pittsburgh compound-B (PIB),
      amyloid-beta (Abeta)(42), tau, and phosphorylated tau (ptau)(181) biomarkers.
      METHODS: Sixty-nine older adults (17 males, 52 females) aged 55 to 88 years, were
      recruited and confirmed to be cognitively normal. A questionnaire on physical
      exercise levels over the past decade was administered to all. Cerebrospinal fluid
      samples were collected from 56 participants, and amyloid imaging with PIB was
      performed on 54 participants. RESULTS: Participants were classified based on
      biomarker levels. Those with elevated PIB (p = 0.030), tau (p = 0.040), and
      ptau(181) (p = 0.044) had significantly lower exercise, with a nonsignificant
      trend for lower Abeta(42) (p = 0.135) to be associated with less exercise.
      Results were similar for PIB after controlling for covariates; tau (p = 0.115)
      and ptau(181) (p = 0.123) differences were reduced to nonsignificant trends.
      Additional analyses also demonstrated that active individuals who met the
      exercise guidelines set by the American Heart Association had significantly lower
      PIB binding and higher Abeta(42) levels with and without controlling for
      covariates (PIB: p = 0.006 and p = 0.001; Abeta(42): p = 0.042 and p = 0.046).
      Last, the associations between exercise engagement and PIB levels were more
      prominent in APOE epsilon 4 noncarriers. INTERPRETATION: Collectively, these
      results are supportive of an association between exercise engagement and AD
      biomarkers in cognitively normal older adults.

PMID- 20818790
TI  - Erythropoietin plus insulin-like growth factor-I protects against neuronal damage
      in a murine model of human immunodeficiency virus-associated neurocognitive
      disorders.
AB  - OBJECTIVE: Prolonged human immunodeficiency virus-1 (HIV-1) infection leads to
      neurological debilitation, including motor dysfunction and frank dementia.
      Although pharmacological control of HIV infection is now possible, HIV-associated
      neurocognitive disorders (HAND) remain intractable. Here, we report that chronic
      treatment with erythropoietin (EPO) and insulin-like growth factor-I (IGF-I)
      protects against HIV/gp120-mediated neuronal damage in culture and in vivo.
      METHODS: Initially, we tested the neuroprotective effects of various
      concentrations of EPO, IGF-I, or EPO+IGF-I from gp120-induced damage in vitro. To
      assess the chronic effects of EPO+IGF-I administration in vivo, we treated
      HIV/gp120-transgenic or wild-type mice transnasally once a week for 4 months and
      subsequently conducted immunohistochemical analyses. RESULTS: Low concentrations
      of EPO+IGF-I provided neuroprotection from gp120 in vitro in a synergistic
      fashion. In vivo, EPO+IGF-I treatment prevented gp120-mediated neuronal loss, but
      did not alter microgliosis or astrocytosis. Strikingly, in the brains of both
      humans with HAND and gp120-transgenic mice, we found evidence for
      hyperphosphorylated tau protein (paired helical filament-I tau), which has been
      associated with neuronal damage and loss. In the mouse brain following transnasal
      treatment with EPO+IGF-I, in addition to neuroprotection we observed increased
      phosphorylation/activation of Akt (protein kinase B) and increased
      phosphorylation/inhibition of glycogen synthase kinase (GSK)-3beta, dramatically
      decreasing downstream hyperphosphorylation of tau. These results indicate that
      the peptides affected their cognate signaling pathways within the brain
      parenchyma. INTERPRETATION: Our findings suggest that chronic combination therapy
      with EPO+IGF-I provides neuroprotection in a mouse model of HAND, in part,
      through cooperative activation of phosphatidylinositol 3-kinase/Akt/GSK-3beta
      signaling. This combination peptide therapy should therefore be tested in humans
      with HAND.

PMID- 20818792
TI  - JC virus persistence following progressive multifocal leukoencephalopathy in
      multiple sclerosis patients treated with natalizumab.
AB  - JC virus (JCV) DNA in the cerebrospinal fluid (CSF) provides the laboratory
      confirmatory diagnosis of progressive multifocal leukoencephalopathy (PML) in
      patients whose clinical symptoms and magnetic resonance imaging findings are
      consistent with PML.The Laboratory of Molecular Medicine and Neuroscience (LMMN),
      National Institute of Neurological Disorders and Stroke (NINDS), National
      Institutes of Health (NIH), made the confirmatory laboratory diagnosis in 35
      multiple sclerosis (MS) patients treated with natalizumab. Thirteen patients had
      3 or more CSF samples taken from weeks to months following PML diagnosis. Seven
      of the 13 patients demonstrated persistence of JCV DNA in the CSF even though all
      patients experienced immune reconstitution inflammatory syndrome (IRIS), 11
      patients had plasma exchange, and 2 had immunoabsorption. Specific anti-JCV
      antibody was measured in plasma/sera samples from 25 of the 35 patients. Most of
      the samples showed moderate to high or rising antibody levels from the time of
      PML diagnosis. However, plasma from 1 patient at or near the time of PML
      diagnosis had a titer considered seronegative and 2 other plasma samples from
      patients had titers considered at baseline for seropositivity. In several PML
      cases, viral persistence and neurological deficits have continued for several
      years, indicating that once initiated, JCV infection may not entirely clear, even
      with IRIS.

PMID- 20818791
TI  - Role of interleukin-1beta in postoperative cognitive dysfunction.
AB  - OBJECTIVE: Although postoperative cognitive dysfunction (POCD) often complicates
      recovery from major surgery, the pathogenic mechanisms remain unknown. We
      explored whether systemic inflammation, in response to surgical trauma, triggers
      hippocampal inflammation and subsequent memory impairment, in a mouse model of
      orthopedic surgery. METHODS: C57BL/6J, knock out (lacking interleukin [IL]-1
      receptor, IL-1R(-/-)) and wild type mice underwent surgery of the tibia under
      general anesthesia. Separate cohorts of animals were tested for memory function
      with fear conditioning tests, or euthanized at different times to assess levels
      of systemic and hippocampal cytokines and microglial activation; the effects of
      interventions, designed to interrupt inflammation (specifically and
      nonspecifically), were also assessed. RESULTS: Surgery caused hippocampal
      dependent memory impairment that was associated with increased plasma cytokines,
      as well as reactive microgliosis and IL-1beta transcription and expression in the
      hippocampus. Nonspecific attenuation of innate immunity with minocycline
      prevented surgery-induced changes. Functional inhibition of IL-1beta, both in
      mice pretreated with IL-1 receptor antagonist and in IL-1R(-/-) mice, mitigated
      the neuroinflammatory effects of surgery and memory dysfunction. INTERPRETATION:
      A peripheral surgery-induced innate immune response triggers an IL-1beta-mediated
      inflammatory process in the hippocampus that underlies memory impairment. This
      may represent a viable target to interrupt the pathogenesis of postoperative
      cognitive dysfunction.

PMID- 20818793
TI  - Natalizumab dosage suspension: are we helping or hurting?
AB  - The risk of developing progressive multifocal leukoencephalopathy increases with
      the duration of treatment with natalizumab. Planned dosage interruptions have
      been proposed as a means of decreasing cumulative risk. The clinical consequences
      of dosage interruption were evaluated in a single center cohort of natalizumab
      treated patients. Medical records were reviewed for 84 patients identified with
      multiple sclerosis who received 12 or more infusions of natalizumab at an
      academic multiple sclerosis center. Eighty-one percent (68/84) underwent a dosage
      interruption, and 19% (16/84) had no interruption in natalizumab treatment. Of
      those with a treatment interruption, 27.9% (19/68) experienced a clinical relapse
      within 6 months of the suspension, whereas none of the patients with ongoing
      treatment experienced a flare during months 12 to 18 of treatment (p = 0.017,
      Fisher exact test). Survival analysis showed that Kaplan-Meier curves comparing
      dosage interruption to ongoing treatment diverged (p = 0.025). Median time from
      treatment interruption to relapse onset was 3 months. No clinical predictors
      associated with an increased risk of developing flares during dosage interruption
      were identified. Among the 19 patients who had a flare, 7 had severe flares, with
      a mean number of 16 Gad+ lesions on brain magnetic resonance imaging (range, 6
      40). Their median Expanded Disability Status Scale at natalizumab interruption
      was 3.0 and increased to 6.0 during the flare (p = 0.0008). Natalizumab dosage
      interruption is associated with clinical flares and return of radiographic
      inflammatory disease activity. Some of these flares can be clinically severe,
      with a high number of contrast-enhanced lesions, suggesting a possible rebound of
      disease activity.

PMID- 20818794
TI  - Central facial palsy revisited: a clinical-radiological study.
AB  - We investigated the pattern of volitional facial motor deficits in acute stroke
      patients. We assessed the strength of single facial movements and correlated it
      to the site of infarct classified on computed tomography scans. Exclusion
      criteria were previous stroke, cerebral hemorrhage, and subcortical stroke.
      Results showed that weakness in eyelid closure was associated with anterior
      cerebral artery (ACA) stroke. Weakness in lip opening was associated with middle
      cerebral artery (MCA) stroke. We suggest that sparing of upper facial movements
      in MCA stroke is due to the presence of an upper face motor representation in
      both the MCA and ACA territories.

PMID- 20818795
TI  - Considerations on discontinuing natalizumab for the treatment of multiple
      sclerosis.

PMID- 20818797
TI  - Study on the mechanism of potential response of a ketamine-sensitive membrane
      electrode.
AB  - The response mechanism of a simple device for the rapid detection of ketamine
      with 'in the field' capabilities is investigated. The mechanism is a membranous
      ketamine ionic selective electrode (ISE) with partly carboxylated PVC as matrix
      and ortho-nitrophenyloctyl ether (o-NPOE) as plasticizer. The experimental
      results reveal that the inclusion of the plasticizer in the membrane
      significantly increased the response. A mechanism is proposed where the
      infiltration of a target species into the membrane is capable of producing a
      superior response. This response process is non-selective for species with
      similar molecular structure and size. This new research addresses some omissions
      and misapprehension in the literature where the mechanism was reported as an ion
      exchange-induced response. In this research the ion-exchange-induced response was
      measurable after the elimination of the infiltration-induced response extending
      to lower concentration ranges and thus providing the potential for better
      sensitivity and selectivity.

PMID- 20818798
TI  - Monitoring the allyl ester deprotection by HR MAS NMR in BAL-solid phase peptide
      synthesis.
AB  - The backbone amide linker strategy, in which the growing peptide chain is
      anchored to a solid support via a backbone amide nitrogen, has proven to be
      successful for the synthesis of cyclic peptides. Optimisation of the reaction
      conditions for the synthesis of c(Gly-Trp-betaAla-Phe) could be accomplished by
      the help of high resolution magic angle spinning (HR MAS) NMR and the results are
      presented here. Signal vanishing of HR MAS NMR resonances were encountered and
      proven to be originated from interchain aggregations of peptide chains.

PMID- 20818799
TI  - A rapid screening LC-MS/MS method based on conventional HPLC pumps for the
      analysis of low molecular weight xenobiotics: application to doping control
      analysis.
AB  - This study presents a fast multi-analyte screening method specifically developed
      for the detection of xenobiotics in urine. The proposed method allows the
      screening of several classes of substance in a single chromatographic method with
      a run-time of 11 min, inclusive of post-run and reconditioning times.
      Chromatographic separation is achieved in 7.2 min using a reversed-phase 2.7 um
      fused-core particle column, generating a back-pressure not exceeding 400 bar and
      therefore enabling the use of traditional high performance liquid chromatography
      (HPLC) instruments. The effectiveness of this approach was evaluated, by liquid
      chromatography tandem mass spectrometry (LC-MS/MS) in positive electrospray
      ionization, using 20 blank urine samples spiked with 45 compounds prohibited in
      sport: 11 diuretics, 16 glucocorticoids, 9 stimulants, 5 anti-oestrogens, as well
      as formoterol, carboxy-finasteride (previously prohibited by the World Anti
      Doping Agency (WADA) in 2008), gestrinone and tetrahydrogestrinone. Qualitative
      validation shows the proposed method to be specific with no significant
      interference. All of the analytes considered in this study were clearly
      distinguishable in urine, with limits of detection ranging from 5 ng/mL to 350
      ng/mL, significantly below the Minimum Required Performance Levels (MRPL) set by
      WADA for the accredited sports anti-doping laboratories. All compounds of
      interest were separated, including synthetic and endogenous glucocorticoids with
      similar retention times and fragmentation patterns.

PMID- 20818800
TI  - Guidelines for European workplace drug and alcohol testing in hair.
AB  - Drug and alcohol abuse is a concern for many European companies, especially those
      having safety-critical jobs. It is not uncommon for European companies to
      establish a drug policy with little or no provision for drug testing. The
      European Union (EU) has launched a number of initiatives in its fight against
      drugs. There is, however, no specific EU legislation and no generally accepted
      guidelines. Since the outcome of workplace drug testing (WDT) can have serious
      consequences for the employee, it is of utmost importance that WDT be performed
      in a defined quality standard and in a legally secured way. In order to fulfil
      this, the European Workplace Drug Testing Society (EWDTS) has formulated WDT
      guidelines in order to ensure that the entire drug testing process is of high
      quality, accredited, and legally defensible, hence giving accurate and reliable
      information about employee drug use while respecting the privacy of the employee.
      The aim of this paper is to present the recently formulated guidelines for
      workplace drug testing in hair.

PMID- 20818801
TI  - Contribution of first-principles calculations to multinuclear NMR analysis of
      borosilicate glasses.
AB  - Boron-11 and silicon-29 NMR spectra of xSiO(2)-(1-x)B(2)O(3) glasses (x=0.40,
      0.80 and 0.83) have been calculated using a combination of molecular dynamics
      (MD) simulations with density functional theory (DFT) calculations of NMR
      parameters. Structure models of 200 atoms have been generated using classical
      force fields and subsequently relaxed at the PBE-GGAlevel of DFT theory. The
      gauge including projector augmented wave (GIPAW) method is then employed for
      computing the shielding and electric field gradient tensors for each silicon and
      boron atom. Silicon-29 MAS and boron-11 MQMAS NMR spectra of two glasses (x=0.40
      and 0.80) have been acquired and theoretical spectra are found to well agree with
      the experimental data. For boron-11, the NMR parameter distributions have been
      analysed using a Kernel density estimation (KDE) approach which is shown to
      highlight its main features. Accordingly, a new analytical model that
      incorporates the observed correlations between the NMR parameters is introduced.
      It significantly improves the fit of the (11)B MQMAS spectra and yields,
      therefore, more reliable NMR parameter distributions. A new analytical model for
      a quantitative description of the dependence of the silicon-29 and boron-11
      isotropic chemical shift upon the bond angles is proposed, which incorporates
      possibly the effect of SiO(2)-B(2)O(3) intermixing. Combining all the above
      procedures, we show how distributions of Si-O-T and B-O-T (T=Si, B) bond angles
      can be estimated from the distribution of isotropic chemical shift of silicon-29
      and boron-11, respectively.

PMID- 20818802
TI  - Electric field gradient calculations in paramagnetic compounds using the PAW
      approach. Application to 23Na NMR in layered vanadium phosphates.
AB  - This article presents ab initio calculations of electric field gradient (EFG)
      parameters as a tool for the structural characterization of paramagnetic
      crystalline compounds. Previously reported 23Na NMR parameters of vanadium + IV
      containing vanado-phosphate compounds were computed within density functional
      theory using both cluster and fully periodic approaches. Quadrupolar parameter
      values measured by 23Na NMR experiments were reproduced with a level of accuracy
      comparable to that achievable in diamagnetic compounds and allowed the assignment
      of observed 23Na NMR signals. This work demonstrates the utility of the periodic
      planewave pseudopotential + PAW approach for the calculation of EFG parameters in
      paramagnetic compounds.

PMID- 20818803
TI  - 15N chemical shifts of a series of isatin oxime ethers and their corresponding
      nitrone isomers.
AB  - In this article, we describe the characteristic (15)N chemical shifts of isatin
      oxime ethers and their isomer nitrone. These oxime ethers and nitrones are the
      alkylation reaction products of isatin oximes. In our study, the (15)N chemical
      shifts observed in these oxime ethers were in the 402-408 (or 22-28) ppm range,
      although those for their corresponding nitrone series were in the 280-320 (or 
      100 to -60) ppm range. This remarkable difference in (15)N NMR chemical shift
      values could potentially be used to determine the O- versus N-alkylation of
      oximes, even when only one isomer is available. In this paper, the differences in
      (15)N NMR chemical shifts serve as the basis for a discussion about how to
      distinguish both regioisomers derived from the oximes alkylation.

PMID- 20818804
TI  - Glycated albumin, a precursor of advanced glycation end-products, up-regulates
      NADPH oxidase and enhances oxidative stress in human endothelial cells: molecular
      correlate of diabetic vasculopathy.
AB  - BACKGROUND: Hyperglycaemia induces non-enzymatic glycation reactions in proteins
      which generate Amadori products and advanced glycation end-products; the latter
      are thought to participate in the vascular complications of diabetic patients.
      However, the exact mechanisms concerning the effects of glycated proteins on
      vascular tissue remain to be determined. Therefore, the effects of glycated human
      serum albumin on human umbilical vein endothelial cells were studied. METHODS:
      Reactive oxygen species production was measured by the cytochrome C reduction
      method and by 5(6)-carboxy-2',7'-dichlorofluorescein diacetate (c-DCF-DA)
      fluorescence after treating human umbilical vein endothelial cells with glycated
      human serum albumin (6-200 ug/mL). The expression of Nox4 and p22phox mRNAs were
      analysed by reverse transcription-quantitative polymerase chain reactions and the
      levels of their proteins were measured by immunofluorescence. RESULTS: Low
      concentrations of glycated human serum albumin enhanced reactive oxygen species
      production in human umbilical vein endothelial cells after 4 h of treatment at
      both extracellular and intracellular sites. This enhanced production was
      sustained, although to a lesser extent, after 6 and 12 h of treatment. The gene
      expression study revealed that Nox4 and p22phox mRNA levels were elevated after 4
      h of treatment with glycated human serum albumin. This mRNA elevation and
      enhanced reactive oxygen species production correlated with an increased
      expression of the Nox4 protein. CONCLUSIONS: The results revealed that a
      circulating and abundant modified glycated human serum albumin protein in
      diabetic patients induced a sustained reactive oxygen species production in human
      endothelial cells. This effect may have been due to an up-regulation of Nox4, the
      main subunit of NADPH oxidase in the endothelium.

PMID- 20818805
TI  - Gene therapy and enhancement for diabetes (and other diseases): the multiplicity
      of considerations.
AB  - Gene therapy has reached the forefront of studies and research over the last 30
      years because of its potential for curing, treating, and preventing diseases
      associated with DNA mutations. Type 1 and type 2 diabetes are two examples of
      very common polygenic and multifactorial diseases. The huge amount of scientific
      literature on this topic reflects a growing general interest in the possibilities
      of altering our genetic heritage and thus controlling the onset of diseases
      associated with mutations and relative risk factors. We have focussed on the new
      treatment opportunities and possibility of enhancing an individual's health,
      physical well-being, and even an individual's behaviour through technologies
      specially designed for therapeutic purposes, which have been presented in
      literature. This historical perspective shows how this type of research, however,
      was immediately subjected to an ethical evaluation, especially regarding the
      decoding of the human genome and the questions raised by the alteration of our
      genetic heritage through new biotechnologies. Moreover, understanding the
      limitations of gene therapy protocol experiments and the multifactorial nature of
      many diseases, which have a genetic base, also contributes to these
      considerations.

PMID- 20818806
TI  - Complex mixture analysis of organic compounds in green coffee bean extract by two
      dimensional NMR spectroscopy.
AB  - A complex mixture analysis by one- and two-dimensional nuclear magnetic resonance
      (NMR) spectroscopy was carried out for the first time for the identification and
      quantification of organic compounds in green coffee bean extract (GCBE). A
      combination of (1)H-(1)H DQF-COSY, (1)H-(13)C HSQC, and (1)H-(13)C CT-HMBC two
      dimensional sequences was used, and 16 compounds were identified. In particular,
      three isomers of caffeoylquinic acid were identified in the complex mixture
      without any separation. In addition, GCBE components were quantified by the
      integration of carbon signals by use of a relaxation reagent and an inverse-gated
      decoupling method without a nuclear Overhauser effect. This NMR methodology
      provides detailed information about the kinds and amounts of GCBE components, and
      in our study, the chemical makeup of GCBE was clarified by the NMR results.

PMID- 20818807
TI  - Obstructive sleep apnea syndrome and fatty liver: association or causal link?
AB  - Obstructive sleep apnea (OSA) is a complex disorder that consists of upper airway
      obstruction, chronic intermittent hypoxia and sleep fragmentation. OSA is well
      known to be associated with hypoxia, insulin resistance and glucose intolerance,
      and these factors can occur in the presence or absence of obesity and metabolic
      syndrome. Although it is well established that insulin resistance, glucose
      intolerance and obesity occur frequently with non-alcoholic fatty liver disease
      (NAFLD), it is now becoming apparent that hypoxia might also be important in the
      development of NAFLD, and it is recognized that there is increased risk of NAFLD
      with OSA. This review discusses the association between OSA, NAFLD and
      cardiovascular disease, and describes the potential role of hypoxia in the
      development of NAFLD with OSA.

PMID- 20818808
TI  - Endoscopic ultrasound in chronic pancreatitis: where are we now?
AB  - Endoscopic ultrasonography (EUS) is well suited for assessment of the pancreas
      due to its high resolution and the proximity of the transducer to the pancreas,
      avoiding air in the gut. Evaluation of chronic pancreatitis (CP) was an early
      target for EUS, initially just for diagnosis but later for therapeutic purposes.
      The diagnosis of CP is still accomplished using the standard scoring based on
      nine criteria, all considered to be of equal value. For diagnosis of any CP, at
      least three or four criteria must be fulfilled, but for diagnosis of severe CP at
      least six criteria are necessary. The Rosemont classification, more restrictive,
      aims to standardize the criteria and assigns different values to different
      features, but requires further validation. EUS-fine needle aspiration (EUS-FNA)
      is less advisable for diagnosis of diffuse CP due to its potential side effects.
      Elastography and contrast-enhanced EUS are orientation in differentiating a focal
      pancreatic mass in a parenchyma with features of CP, but they cannot replace EUS
      FNA. The usefulness of EUS-guided celiac block for painful CP is still being
      debated with regard to the best technique and the indications. EUS-guided
      drainage of pseudocysts is preferred in non-bulging pseudocysts or in the
      presence of portal hypertension. EUS-guided drainage of the main pancreatic duct
      should be reserved for cases in which endoscopic retrograde
      cholangiopancreatography has failed owing to difficult cannulation of the papilla
      or difficult endotherapy. It should be performed only by highly skilled
      endoscopists, due to the high rate of complications.

PMID- 20818809
TI  - Intestinal epithelial cells in inflammatory bowel diseases.
AB  - The pathogenesis of inflammatory bowel diseases (IBDs) seems to involve a primary
      defect in one or more of the elements responsible for the maintenance of
      intestinal homeostasis and oral tolerance. The most important element is
      represented by the intestinal barrier, a complex system formed mostly by
      intestinal epithelial cells (IECs). IECs have an active role in producing mucus
      and regulating its composition; they provide a physical barrier capable of
      controlling antigen traffic through the intestinal mucosa. At the same time, they
      are able to play the role of non-professional antigen presenting cells, by
      processing and presenting antigens directly to the cells of the intestinal immune
      system. On the other hand, immune cells regulate epithelial growth and
      differentiation, producing a continuous bi-directional cross-talk within the
      barrier. Several alterations of the barrier function have been identified in IBD,
      starting from mucus features up to its components, from epithelial junctions up
      to the Toll-like receptors, and altered immune responses. It remains to be
      understood whether these defects are primary causes of epithelial damage or
      secondary effects. We review the possible role of the epithelial barrier and
      particularly describe the role of IECs in the pathogenesis of IBD.

PMID- 20818810
TI  - alpha,beta-amyrin, a natural triterpenoid ameliorates L-arginine-induced acute
      pancreatitis in rats.
AB  - AIM: To study the beneficial effects of triterpene alpha,beta-amyrin and the
      underlying mechanisms in an experimental pancreatitis model. METHODS: Acute
      pancreatitis was induced in five groups of rats (n = 8) by L-arginine (2 x 2.5
      g/kg, intraperitoneal, 1 h apart) and 1 h later, they received a single oral dose
      of alpha,beta-amyrin (10, 30 and 100 mg/kg), methylprednisolone (30 mg/kg) and
      vehicle (3% Tween 80). A saline (0.9% NaCl) treated group served as a normal
      control. Efficacy was assessed at 24 h by determination of serum levels of
      amylase, lipase and pro-inflammatory cytokines [tumor necrosis factor (TNF)-alpha
      and interleukin (IL)-6], pancreatic myeloperoxidase (MPO) activity, lipid
      peroxidation [thiobarbituric acid reactive substances (TBARS)], nitrate/nitrite
      levels, and the wet weight/body weight ratio. Tissue histology and the
      immunoreactivity for TNF-alpha and inducible nitric oxide synthetase (iNOS) were
      performed. RESULTS: alpha,beta-amyrin and methylprednisolone treatments
      significantly (P < 0.05) attenuated the L-arginine-induced increases in
      pancreatic wet weight/body weight ratio, and decreased the serum levels of
      amylase and lipase, and TNF-alpha and IL-6, as compared to the vehicle control.
      Also, pancreatic levels of MPO activity, TBARS, and nitrate/nitrite were
      significantly lower. Histological findings and TNF-alpha and iNOS immunostaining
      further confirmed the amelioration of pancreatic injury by alpha,beta-amyrin.
      CONCLUSION: alpha,beta-amyrin has the potential to combat acute pancreatitis by
      acting as an anti-inflammatory and antioxidant agent.

PMID- 20818812
TI  - Peripancreatic collections in acute pancreatitis: correlation between
      computerized tomography and operative findings.
AB  - AIM: To evaluate the ability of contrast-enhanced computerized tomography (CECT)
      to characterize the nature of peripancreatic collections. METHODS: Twenty five
      patients with peripancreatic collections on CECT and who underwent operative
      intervention for severe acute pancreatitis were retrospectively studied. The
      collections were classified into (1) necrosis without frank pus; (2) necrosis
      with pus; and (3) fluid without necrosis. A blinded radiologist assessed the
      preoperative CTs of each patient for necrosis and peripancreatic fluid
      collections. Peripancreatic collections were described in terms of volume,
      location, number, heterogeneity, fluid attenuation, wall perceptibility, wall
      enhancement, presence of extraluminal gas, and vascular compromise. RESULTS:
      Fifty-four collections were identified at operation, of which 45 (83%) were
      identified on CECT. Of these, 25/26 (96%) had necrosis without pus, 16/19 (84%)
      had necrosis with pus, and 4/9 (44%) had fluid without necrosis. Among the study
      characteristics, fluid heterogeneity was seen in a greater proportion of
      collections in the group with necrosis and pus, compared to the other two groups
      (94% vs 48% and 25%, P = 0.002 and 0.003, respectively). Among the wall
      characteristics, irregularity was seen in a greater proportion of collections in
      the groups with necrosis with and without pus, when compared to the group with
      fluid without necrosis (88% and 71% vs 25%, P = 0.06 and P < 0.01, respectively).
      The combination of heterogeneity and presence of extraluminal gas had a
      specificity and positive likelihood ratio of 92% and 5.9, respectively, in
      detecting pus. CONCLUSION: Most of the peripancreatic collections seen on CECT in
      patients with severe acute pancreatitis who require operative intervention
      contain necrotic tissue. CECT has a somewhat limited role in differentiating the
      different types of collections.

PMID- 20818811
TI  - Antitumor effect of matrine in human hepatoma G2 cells by inducing apoptosis and
      autophagy.
AB  - AIM: To study the antitumor effect of matrine in human hepatoma G2 (HepG2) cells
      and its molecular mechanism involved in antineoplastic activities. METHODS: 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used
      to detect viability of HepG2 cells. The effect of matrine on cell cycle was
      detected by fl ow cytometry. Annexin-V-FITC/PI double staining assay was used to
      detect cellular apoptosis. Cellular morphological changes were observed under an
      inverted phase contrast microscope. Transmission electron microscopy was
      performed to further examine ultrastructural structure of the cells treated with
      matrine. Monodansylcadaverine (MDC) staining was used to detect autophagy.
      Whether autophagy is blocked by 3-methyladenine (3-MA), an autophagy inhibitor,
      was evaluated. Expression levels of Bax and Beclin 1 in HepG2 cells were measured
      by real-time quantitative reverse transcription-polymerase chain reaction (RT
      PCR). RESULTS: Matrine significantly inhibited the proliferation of HepG2 cells
      in a dose- and time-dependent manner, and induced G1-phase cell cycle arrest and
      apoptosis of HepG2 cells in a dose-dependent manner. The total apoptosis rate was
      0.14% for HepG2 cells not treated with matrine. In contrast, the apoptosis rate
      was 28.91%, 34.36% and 38.80%, respectively, for HepG2 cells treated with matrine
      at the concentration of 0.5, 1.0 and 2.0 mg/mL. The remarkable morphological
      changes were observed under an inverted phase contrast microscope. Abundant
      cytoplasmic vacuoles with varying sizes were observed in HepG2 cells treated with
      matrine. Furthermore, vacuolization in cytoplasm progressively became larger and
      denser when the concentration of matrine was increased. Electron microscopy
      demonstrated formation of abundant autophagic vacuoles in HepG2 cells after
      matrine treatment. When the specific autophagic inhibitor, 3-MA, was applied, the
      number of autophagic vacuoles greatly decreased. MDC staining showed that the
      fluorescent density was higher and the number of MDC-labeled particles in HepG2
      cells was greater in matrine treatment group than in control group. Fewer
      autophagic vacuoles were observed in the combined 3-MA and matrine treatment
      group when 3-MA was added before matrine treatment, indicating that both
      autophagy and apoptosis are activated when matrine-induced death of hepatoma G2
      cells occurs. Real-time quantitative RT-PCR revealed that the expression levels
      of Bax gene, an apoptosis-related molecule, and Beclin 1 gene which plays a key
      role in autophagy were higher in matrine treatment group than in control group,
      indicating that Beclin 1 is involved in matrine-induced autophagy and the pro
      apoptotic mechanism of matrine may be related to its upregulation of Bax
      expression. CONCLUSION: Matrine has potent antitumor activities in HepG2 cells
      and may be used as a novel effective reagent in treatment of hepatocellular
      carcinoma.

PMID- 20818813
TI  - Pre-illness changes in dietary habits and diet as a risk factor for inflammatory
      bowel disease: a case-control study.
AB  - AIM: To evaluate whether symptoms of inflammatory bowel disease (IBD), before
      diagnosis modify dietary habits, and to investigate the pre-illness diet in
      patients with recent IBD in comparison with an age-matched healthy control group.
      METHODS: Overall, 83 new cases of IBD (41 ulcerative colitis, 42 Crohn's disease)
      and 160 healthy controls were studied. Portions per week of 34 foods and
      beverages before onset of symptoms were recorded using a validated questionnaire.
      Duration of symptoms before IBD diagnosis, presence of specific symptoms and
      their impact on subjective changes in usual dietary habits were also recorded.
      The association between diet and IBD was investigated by multiple logistic
      regression and dietary patterns were assessed by factor analysis. RESULTS:
      Changes in dietary habits, due to the presence of symptoms, were reported by
      38.6% of patients and were not significantly related to specific symptoms, rather
      to long duration of symptoms, only in Crohn's disease patients. In IBD patients
      who did not change dietary habits, moderate and high consumption of margarine (OR
      = 11.8 and OR = 21.37) was associated with ulcerative colitis, whilst high
      consumption of red meat (OR = 7.8) and high intake of cheese were associated with
      Crohn's disease. CONCLUSION: More than one third of IBD patients change dietary
      habits before diagnosis. Margarine, red meat and cheese increase the risk of
      ulcerative colitis and Crohn's disease.

PMID- 20818814
TI  - Exertional esophageal pH-metry and manometry in recurrent chest pain.
AB  - AIM: To investigate the diagnostic efficacy of 24-h and exertional esophageal pH
      metry and manometry in patients with recurrent chest pain. METHODS: The study
      included 111 patients (54% male) with recurrent angina-like chest pain, non
      responsive to therapy with proton pump inhibitors. Sixty-five (59%) had non
      obstructive lesions in coronary artery angiography, and in 46 (41%) significant
      coronary artery narrowing was found. In all patients, 24-h esophageal pH-metry
      and manometry, and treadmill stress tests with simultaneous esophageal pH-metry
      and manometry monitoring were performed. During a 24-h examination the percentage
      of spontaneous chest pain (sCP) episodes associated with acid reflux or
      dysmotility (symptom index, SI) was calculated. Patients with SI > 50% for acid
      gastroesophageal reflux (GER) were classified as having GER-related sCP. The
      remaining symptomatic individuals were determined as having non-GER-related sCP.
      During the stress test, the occurrence of chest pain, episodes of esophageal
      acidification (pH < 4 for 10 s) and esophageal spasm with more than 55% of
      simultaneous contractions (exercise-provoked esophageal spasm or EPES) were
      noted. RESULTS: Sixty-eight (61%) individuals reported sCP during 24-h esophageal
      function monitoring. Eleven of these (16%) were classified as having GER-related
      sCP and 53/68 (84%) as having non-GER-related sCP. The exercise-provoked chest
      pain during a stress test occurred in 13/111 (12%) subjects. In order to compare
      the clinical usefulness of 24-h esophageal function monitoring and its
      examination limited only to the treadmill stress test, the standard parameters of
      diagnostic test evaluation were determined. The occurrence of GER-related or non
      GER-related sCP was assumed as a "gold standard". Afterwards, accuracy,
      sensitivity and specificity were calculated. These parameters expressed a
      prediction of GER-related or non-GER-related sCP occurrence by the presence of
      chest pain, esophageal acidification and EPES. Accuracy, sensitivity and
      specificity of chest pain during the stress test predicting any sCP occurrence
      were 28%, 35% and 80%, respectively, predicting GER-related sCP were 42%, 0% and
      83%, respectively, and predicting non-GER-related sCP were 57%, 36% and 83%,
      respectively. Similar values were obtained for exercise-related acidification
      with pH < 4 longer than 10 s in the prediction of GER-related sCP (44%, 36% and
      92%, respectively) and EPES in relation to non-GER-related sCP (48%, 23% and 84%,
      respectively). CONCLUSION: The presence of chest pain, esophageal acidification
      and EPES had greater than 80% specificity to exclude the GER-related and non-GER
      related causes of recurrent chest pain.

PMID- 20818815
TI  - Effects of glutamine and curcumin on bacterial translocation in jaundiced rats.
AB  - AIM: To investigate the effect of curcumin on bacterial translocation and
      oxidative damage in an obstructive jaundice model and compare the results to
      glutamine, an agent known to be effective and clinically used. METHODS: Twenty
      four female Wistar-Albino rats, weighing 200-250 g, were randomly divided into
      three groups (8 in each group). After ligation of the common bile duct in all
      animals, Group I received oral normal saline, Group II received oral glutamine
      and Group III received oral curcumin for seven days. Blood samples via cardiac
      puncture, tissue samples (terminal ileum, liver and mesenteric lymph node) and
      peritoneal fluid were obtained from the animals at the time of death to
      investigate bacterial translocation and oxidative damage. RESULTS: We observed
      that both glutamine and curcumin reduced bacterial translocation in blood,
      hepatocellular damage, plasma cytokine levels, oxidative tissue damage and
      apoptosis significantly compared to the control group. Additionally, glutamine
      showed protective effects on ileal epithelium and reduced villus atrophy.
      CONCLUSION: On the basis of these findings, both curcumin and glutamine are
      thought to be effective in preventing or reducing bacterial translocation and
      oxidative damage in obstructive jaundice.

PMID- 20818816
TI  - HCV genotype distribution and possible transmission risks in Lahore, Pakistan.
AB  - AIM: To investigate the prevalence of hepatitis C virus (HCV) genotypes and their
      association with possible transmission routes in the general population of
      Lahore, as the data exclusively related to this city is limited. METHODS:
      Complete data regarding patient's history, possible route of infection and
      biochemical tests was collected from the public hospital for 1364 patients. SPSS
      version 16 windows software was used for data analysis by univariate and
      multivariate techniques. RESULTS: Age range < or = 40 years showed high
      prevalence of HCV infection. HCV genotype 3a was dominant (55.9%), followed by 1a
      (23.6%), 4a (12.5%), 3b (3.2%), untypable (2.5%), 4b (1.2%) and mixed type
      (1.2%). Blood transfusion, dental surgery and barber shops were the main risk
      factors for HCV transmission. Genotype prevalence was independent of age (P =
      0.971) and gender (P = 0.122) while risk factors showed a significant association
      with age (P = 0.000) and genotypes (P = 0.000). We observed an independent
      association of risk factors and genotype 3a, while patients with genotype 1 and 4
      were mostly infected due to dental surgery blood transfusion and barber shops.
      Risk factors of intravenous drug use and sexual exposure were exclusively found
      in < or = 40 years age group. CONCLUSION: An increase in genotypes 1a and 4a
      suggest migration of people, possibly from Balochistan and the northern war-zone
      area. Government should focus on public education regarding infection routes.

PMID- 20818817
TI  - Associated factors for a hyperechogenic pancreas on endoscopic ultrasound.
AB  - AIM: To identify the associated risk factors for hyperechogenic pancreas (HP)
      which may be observed on endoscopic ultrasound (EUS) and to assess the
      relationship between HP and obesity. METHODS: From January 2007 to December 2007,
      we prospectively enrolled 524 consecutive adults who were scheduled to undergo
      EUS. Patients with a history of pancreatic disease or with hepatobiliary or
      advanced gastrointestinal cancer were excluded. Finally, 284 patients were
      included in the analyses. We further analyzed the risk of HP according to the
      categories of visceral adipose tissue (VAT) and subcutaneous adipose tissue in
      132 patients who underwent abdominal computed tomography scans. RESULTS: On
      univariate analysis, age older than 60 years, obesity (body mass index > 25
      kg/m(2)), fatty liver, diabetes mellitus, hypertension and hypercholesterolemia
      were identified as risk factors associated with HP (P < 0.05). On multivariate
      analysis, fatty liver [P = 0.008, odds ratio (OR) = 2.219], male gender (P =
      0.013, OR = 2.636), age older than 60 years (P = 0.001, OR = 2.874) and
      hypertension (P = 0.044, OR = 2.037) were significantly associated with HP. In
      the subgroup analysis, VAT was a statistically significant risk factor for HP (P
      = 0.010, OR = 5.665, lowest quartile vs highest quartile). CONCLUSION: HP
      observed on EUS was associated with fatty liver, male gender, age older than 60
      years, hypertension and VAT.

PMID- 20818818
TI  - Limited endoscopic sphincterotomy plus large balloon dilation for
      choledocholithiasis with periampullary diverticula.
AB  - AIM: To investigate the effectiveness and safety of limited endoscopic
      sphincterotomy (EST) plus large balloon dilation (LBD) for removing
      choledocholithiasis in patients with periampullary diverticula (PAD). METHODS: A
      total of 139 patients with common bile duct (CBD) stones were treated with LBD
      (10-20 mm balloon diameter) after limited EST. Of this total, 73 patients had PAD
      and 66 patients did not have PAD (controls). The results of stone removal and
      complications were retrospectively evaluated. RESULTS: There were no significant
      differences between the PAD and the control groups in overall successful stone
      removal (94.5% vs 93.9%), stone removal in first session (69.9% vs 81.8%),
      mechanical lithotripsy (12.3% vs 13.6%), and complications (11.0% vs 7.6%).
      Clinical outcomes were also similar between the types of PAD, but the rate of
      stone removal in first session and the number of sessions were significantly
      lower and more frequent, respectively, in type B PAD (papilla located near the
      diverticulum) than controls [23/38 (60.5%) vs 54/66 (81.8%), P = 0.021; and 1 (1
      2) vs 1 (1-3), P = 0.037, respectively] and the frequency of pancreatitis was
      significantly higher in type A PAD (papilla located inside or in the margin of
      the diverticulum) than in controls (16.1% vs 3.0%, P = 0.047). CONCLUSION:
      Limited EST plus LBD was an effective and safe procedure for removing
      choledocholithiasis in patients with PAD. However, some types of PAD should be
      managed with caution.

PMID- 20818819
TI  - Pathophysiological significance of gallbladder volume changes in gallstone
      diseases.
AB  - AIM: To study the pathophysiological significance of gallbladder volume (GBV) and
      ejection fraction changes in gallstone patients. METHODS: The fasting GBV of
      gallstone patients with acute cholecystitis (n = 99), chronic cholecystitis (n =
      85) and non-gallstone disease (n = 240) were measured by preoperative computed
      tomography. Direct saline injection measurements of GBV after cholecystectomy
      were also performed. The fasting and postprandial GBV of 65 patients with
      gallstones and chronic cholecystitis and 53 healthy subjects who received health
      examinations were measured by abdominal ultrasonography. Proper adjustments were
      made after the correction factors were calculated by comparing the preoperative
      and postoperative measurements. Pathological correlations between gallbladder
      changes in patients with acute calculous cholecystitis and the stages defined by
      the Tokyo International Consensus Meeting in 2007 were made. Unpaired Student's t
      tests were used. P < 0.05 was deemed statistically significant. RESULTS: The
      fasting GBV was larger in late stage than in early/second stage acute
      cholecystitis gallbladders (84.66 +/- 26.32 cm(3), n = 12, vs 53.19 +/- 33.80
      cm(3), n = 87, P = 0.002). The fasting volume/ejection fraction of gallbladders
      in chronic cholecystitis were larger/lower than those of normal subjects (28.77
      +/- 15.00 cm(3) vs 6.77 +/- 15.75 cm(3), P < 0.0001)/(34.6% +/- 10.6%, n = 65, vs
      53.3% +/- 24.9%, n = 53, P < 0.0001). CONCLUSION: GBV increases as acute
      cholecystitis progresses to gangrene and/or empyema. Gallstone formation is
      associated with poorer contractility and larger volume in gallbladders that
      contain stones.

PMID- 20818820
TI  - Association of NOD1 (CARD4) insertion/deletion polymorphism with susceptibility
      to IBD: a meta-analysis.
AB  - AIM: To find evidences about whether NOD1/CARD4 insertion/deletion polymorphism
      is associated with inflammatory bowel disease by meta-analysis. METHODS: We
      surveyed the studies on the association of NOD1/CARD4 insertion/deletion
      polymorphism with inflammatory bowel disease in PubMed. Meta-analysis was
      performed for genotypes GG/T vs T/T, GG/GG vs T/T, GG/T + GG/GG vs T/T, GG/GG vs
      T/T + GG/T, and GG allele vs T allele in a fixed/random effect model. RESULTS: We
      identified 8 studies (6439 cases and 4798 controls) in Caucasian populations
      using PubMed search. We found no association between NOD1/CARD4
      insertion/deletion polymorphism and inflammatory bowel disease, Crohn's disease,
      and ulcerative colitis. Stratification of cases by age showed that NOD1/CARD4
      insertion/deletion polymorphism was associated with inflammatory bowel disease in
      younger age group at onset (< 40 years) (GG vs T: OR = 0.68, 95% CI: 0.50-0.93, P
      = 0.02; GG/T + GG/GG vs T/T: OR = 0.71, 95% CI: 0.59-0.85, P = 0.0003).
      CONCLUSION: This meta-analysis demonstrates an association between NOD1/CARD4
      insertion/deletion polymorphism and inflammatory bowel disease in the younger age
      group at onset (< 40 years) in Caucasian populations.

PMID- 20818821
TI  - Standard triple, bismuth pectin quadruple and sequential therapies for
      Helicobacter pylori eradication.
AB  - AIM: To compare the effectiveness of standard triple, bismuth pectin quadruple
      and sequential therapies for Helicobacter pylori (H. pylori) eradication in a
      randomized, double-blinded, comparative clinical trial in China. METHODS: A total
      of 215 H. pylori-positive patients were enrolled in the study and randomly
      allocated into three groups: group A (n = 72) received a 10-d bismuth pectin
      quadruple therapy (20 mg rabeprazole bid, 1000 mg amoxicillin bid, 100 mg bismuth
      pectin qid, and 500 mg levofloxacin qd); group B (n = 72) received the sequential
      therapy (20 mg omeprazole bid, 1000 mg amoxicillin bid, in 5 d, followed by 20 mg
      omeprazole bid, 500 mg tinidazole bid, 500 mg clarithromycin bid, for another 5
      d); group C (n = 71) received a standard 1-wk triple therapy (20 mg omeprazole
      bid, 1000 mg amoxicillin bid, 500 mg clarithromycin bid). After all these
      treatments, 20 mg omeprazole bid was administrated for 3 wk. H. pylori status was
      assessed by histology, 13C-urea breath test and rapid urease test at baseline and
      4-6 wk after completion of treatment. Ulcer cicatrization was assessed by
      gastroscopy. chi(2) test (P < 0.05) was used to compare the eradication rates and
      ulcer cicatrisation rates among the three groups. RESULTS: The eradication rate
      was 83.33% (60/72) in group A, 88.89% (64/72) in group B, and 80.56% (58/71) in
      group C. The ulcer cicatrisation rate was 86.44% (51/59) in group A, 90.16%
      (55/61) in group B, and 84.91% (45/53) in group C. The sequential therapy yielded
      a higher eradication rate and ulcer cicatrisation rate than the standard triple
      and bismuth pectin quadruple therapies. Statistically, the eradication rate of
      group B was significantly different from groups A and C (P < 0.05), but the
      difference of ulcer cicatrisation rate and side effects was not statistically
      significant among the three groups (P > 0.05). The three protocols were generally
      well tolerated. CONCLUSION: The sequential therapy has achieved a significantly
      higher eradication rate, and is a more suitable first-line alternative protocol
      for anti-H. pylori infection compared with the standard triple and bismuth pectin
      quadruple therapies.

PMID- 20818822
TI  - Therapy-refractory gastrointestinal motility disorder in a child with c-kit
      mutations.
AB  - Constipation and fecal impaction are frequent and distressing complaints in
      pediatric gastroenterology. Especially in neurologically handicapped children,
      treatment of severe forms of slow-transit constipation (STC) can be difficult. In
      the majority of cases, STC is of unknown etiology. However, in recent years,
      there is growing evidence that interstitial cells of Cajal (ICCs), which serve as
      electrical pacemakers and generate spontaneous electrical slow waves in the
      gastrointestinal tract, might play an important role in the pathophysiology of
      STC. It remains unclear whether morphological ICC alterations seen in affected
      patients are based on congenital developmental anomalies, or whether they are a
      consequence of long-term constipation with secondary damage of the
      gastrointestinal nervous system. To the best of our knowledge, we present the
      first case of a patient with histological alterations in ICC morphology who
      displayed multiple alterations of c-kit at the level of mRNA. The protein encoded
      by c-kit is the receptor tyrosine kinase Kit (CD117), which is crucial for
      development and function of ICCs. Therefore, these findings provide a new
      explanation for congenital alterations of ICC development that result in
      gastrointestinal motility disorders.

PMID- 20818823
TI  - Gastrojejunostomy followed by induction chemotherapy for incurable gastric cancer
      with outlet obstruction.
AB  - A 72-year-old male gastric cancer patient with outlet obstruction underwent
      laparoscopic exploration. The examination disclosed intraperitoneal free cancer
      cells with no overt peritoneal, lymphatic, or hepatic metastasis. The patient
      underwent laparoscopy-assisted gastrojejunostomy (LAGJ) and started chemotherapy
      with S-1 plus cisplatin on postoperative day 13. Three course of the chemotherapy
      shrank the tumor markedly. Then, the patient underwent gastrectomy with a
      curative intent. Laparotomy revealed no intraperitoneal free cancer cells, and
      microscopically complete resection was achieved. The patient received S-1
      chemotherapy as postoperative adjuvant treatment for 1 year, and is still alive
      with no evidence of peritoneal recurrence. LAGJ followed by S-1 plus cisplatin is
      one of the optional treatments that should be considered for patients with outlet
      obstruction as it may widen opportunities for potentially curative resection.

PMID- 20818824
TI  - [Effect of ventilation on infection risk in tuberculosis mass outbreaks at cram
      schools].

PMID- 20818825
TI  - Sensing DNA opening in transcription using quenchable Forster resonance energy
      transfer.
AB  - Many biological processes, such as gene transcription and replication, involve
      opening and closing of short regions of double-stranded DNA (dsDNA). Few
      techniques, however, can study these processes in real time or at the single
      molecule level. Here, we present a Forster resonance energy transfer (FRET) assay
      that monitors the state of DNA (double- vs single-stranded) at a specific region
      within a DNA fragment, at both the ensemble level and the single-molecule level.
      The assay utilizes two closely spaced fluorophores: a FRET donor fluorophore
      (Cy3B) on the first DNA strand and a FRET acceptor fluorophore (ATTO647N) on the
      complementary strand. Because our assay is based on quenching and dequenching
      FRET processes, i.e., the presence or absence of contact-induced fluorescence
      quenching, we have named it a "quenchable FRET" assay or "quFRET". Using lac
      promoter DNA fragments, quFRET allowed us to sense transcription bubble expansion
      and compaction during abortive initiation by bacterial RNA polymerase. We also
      used quFRET to confirm the mode of action of gp2 (a phage-encoded protein that
      acts as a potent inhibitor of Escherichia coli transcription) and rifampicin (an
      antibiotic that blocks transcription initiation). Our results demonstrate that
      quFRET should find numerous applications in many processes involving DNA opening
      and closing, as well as in the development of new antibacterial therapies
      involving transcription.

PMID- 20818826
TI  - Proteomic interrogation of venom delivery in marine cone snails: novel insights
      into the role of the venom bulb.
AB  - Cone snails of the genus Conus are predatory marine gastropods mainly found in
      the shallow waters of the tropics and warm temperate seas. To prey on other
      marine organisms including fish, cone snails have evolved complex venoms
      synthesized and delivered by a highly sophisticated venom apparatus. Upon prey
      discovery, the venom is perfused through a harpoon-like radula tooth and rapidly
      injected into the prey to cause paralysis. While the venom components of cone
      snails have been intensively characterized, the mechanism of venom translocation
      and loading prior to and during injection remains elusive. The involvement of the
      venom bulb, a muscular dilation of the venom gland has been suggested, however
      evidence is sparse. Here, we use a combination of proteomics, molecular biology,
      and morphological examination to elucidate the potential role of the venom bulb
      in venom translocation and delivery. Analysis of the venom bulb proteome clearly
      demonstrated a function of this organ in muscular movement and, more
      interestingly, in burst muscle contraction. Morphological examination revealed
      high structural similarities to the mantle muscle of squids, animals known for
      their rapid escape response. We sequenced and further characterized arginine
      kinase, a key protein of rapid muscular movement in invertebrates and show high
      concentrations of this enzyme in the bulb when compared to the venom gland and
      the foot muscle. Proteins characteristic for venom biosynthesis were low in
      abundance. On the basis of our findings, we suggest that the bulb of cone snails
      is a highly specialized organ of venom translocation. Delivery of venom is driven
      by burst contractions of the bulb rapidly forcing the venom through the radula
      tooth into the prey.

PMID- 20818827
TI  - The first global screening of protein substrates bearing protein-bound 3,4
      Dihydroxyphenylalanine in Escherichia coli and human mitochondria.
AB  - Protein hydroxylation at proline and lysine residues is known to have important
      effects on cellular functions, such as the response to hypoxia. However, protein
      hydroxylation at tyrosine residues (called protein-bound 3,4-dihydroxy
      phenylalanine (PB-DOPA)) has not been carefully examined. Here we report the
      first proteomics screening of the PB-DOPA protein substrates and their sites in
      Escherichia coli and human mitochondria by nano-liquid chromatography/tandem mass
      spectrometry (nano-LC/MS/MS) and protein sequence alignment using the PTMap
      algorithm. Our study identified 67 novel PB-DOPA sites in 43 E. coli proteins and
      9 novel PB-DOPA sites in 7 proteins from HeLa mitochondria. Bioinformatics
      analysis indicates that the structured region is more favored than the
      unstructured regions of proteins for the PB-DOPA modification. The PB-DOPA
      substrates in E. coli were dominantly enriched in proteins associated with
      carbohydrate metabolism. Our study showed that PB-DOPA may be involved in
      regulation of the specific activity of certain evolutionarily conserved proteins
      such as superoxide dismutase and glyceraldehyde 3-phosphate dehydrogenase,
      suggesting the conserved nature of the modification among distant biological
      species. The substrate proteins identified in this study offer a rich source for
      determining their regulatory enzymes and for further characterization of the
      possible contributions of this modification to cellular physiology and human
      diseases.

PMID- 20818828
TI  - Combined proteomic approaches for the identification of specific amino acid
      residues modified by 4-hydroxy-2-nonenal under physiological conditions.
AB  - Proteins modified by 4-hydroxy-2-nonenal (HNE) are cellular markers of oxidative
      stress in health and disease. HNE is generated by free radical chain reactions
      during oxidative stress as a major end-product of the oxidative fatty acid
      metabolism. Identification and quantitative analysis of HNE-modified proteins are
      readily performed by using specific antibodies raised against them. Further on,
      the identification of the amino acid residues involved in the HNE-modification is
      an additional step in proteomic post-transcriptional modification analysis to
      explain the nature of the specificity underlying oxidative stress mechanisms. For
      this purpose, a combined protocol of immune-detection, peptide enrichment, mass
      spectrometry, and de novo protein sequencing has been developed. The methodology
      was first examined in the model protein bovine serum albumin (BSA), allowing the
      comparison of matrix-assisted laser desorption/ionization-tandem time of flight
      (MALDI-TOF/TOF) mass spectrometry and liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) performance and sensitivity. Peptide enrichment was
      optimized by affinity chromatography on HNE-BSA resulting in increased
      sensitivity. Identification of amino acid residues modified by HNE was finally
      ascertained by de novo sequencing analysis. The improved methodology was
      demonstrated on human erythrocyte membrane proteins allowing the identification
      of HNE-lysine and HNE-histidine Michael adducts in the beta-spectrin under
      physiological conditions.

PMID- 20818829
TI  - Wetting and dewetting transition: an efficient toolbox for characterizing low
      energy surfaces.
AB  - The capillary bridge formed between a solid spherical surface and an infinite
      liquid bath is an efficient technique for characterizing the adhesion property of
      a solid surface. When the solid surface is pulled out of the liquid at a
      sufficiently high velocity, a thin liquid film is deposited on the solid and
      drains more slowly than the central capillary bridge. The retraction kinetics of
      this "pancake" and the critical velocity above which it appears are studied as a
      function of the viscosity of the liquid or the wettability of the solids. The
      dynamics of the liquid film follows the classical law of dynamic dewetting. This
      makes the capillary bridge test, used in the dynamical regime, a very efficient
      tool for discriminating between antiadhesive coatings.

PMID- 20818830
TI  - Study of a benzoylperoxy radical in the gas phase: ultraviolet spectrum and
      C6H5C(O)O2 + HO2 reaction between 295 and 357 K.
AB  - This work reports the ultraviolet absorption spectrum and the kinetic
      determinations of the reactions 2C(6)H(5)C(O)O(2) -> products (I) and
      C(6)H(5)C(O)O(2) + HO(2) -> C(6)H(5)C(O)O(2)H + O(2) (IIa), -> C(6)H(5)C(O)OH +
      O(3) (IIb), -> C(6)H(5)C(O)O + OH + O(2) (IIc). Experiments were performed using
      a laser photolysis technique coupled with UV-visible absorption detection over
      the pressure range of 80-120 Torr and the temperature range of 293-357 K. The UV
      spectrum was determined relative to the known cross section of the ethylperoxy
      radical C(2)H(5)O(2) at 250 nm. Kinetic data were obtained by simulating the
      temporal behavior of the UV absorption at 245-260 nm. At room temperature, the
      rate constant value of reaction I (cm(3).molecule(-1).s(-1)) was found to be k(I)
      = (1.5 +/- 0.6) * 10(-11). The Arrhenius expression for reaction II is
      (cm(3).molecule(-1).s(-1)) k(II)(T) = (1.10 +/- 0.20) * 10(-11) exp(364 +/-
      200/T). The branching ratios beta(O3) and beta(OH), respectively, of reactions
      IIb and IIc are evaluated at different temperatures; beta(O3) increases from 0.15
      +/- 0.05 at room temperature to 0.40 +/- 0.05 at 357 K, whereas beta(OH) remains
      constant at 0.20 +/- 0.05. To confirm the mechanism of reaction II, a theoretical
      study was performed at the B3LYP/6-311++G(2d,pd) level of theory followed by CBS
      QB3 energy calculations.

PMID- 20818831
TI  - Population pharmacokinetics of therapeutic monoclonal antibodies.
AB  - A growing number of population pharmacokinetic analyses of therapeutic monoclonal
      antibodies (mAbs) have been published in the scientific literature. The aims of
      this article are to summarize the findings from these studies and to relate the
      findings to the general pharmacokinetic and structural characteristics of
      therapeutic mAbs. A two-compartment model was used in the majority of the
      population analyses to describe the disposition of the mAb. Population estimates
      of the volumes of distribution in the central (V(1)) and peripheral (V(2))
      compartments were typically small, with median (range) values of 3.1 (2.4-5.5) L
      and 2.8 (1.3-6.8) L, respectively. The estimated between-subject variability in
      the V(1) was usually moderate, with a median (range) coefficient of variation
      (CV) of 26% (12-84%). Between-subject variability in other distribution-related
      parameters such as the V(2) and intercompartmental clearance were often not
      estimated. Although the pharmacokinetic models used most frequently in the
      population analyses were models with linear clearance, other models with
      nonlinear, or parallel linear and nonlinear clearance pathways were also applied,
      as many therapeutic mAbs are eliminated via saturable target-mediated mechanisms.
      Population estimates of the maximum elimination rate (V(max)) and the mAb
      concentration at which elimination was at half maximum for Michaelis-Menten-type
      elimination pathways varied considerably among the different therapeutic mAbs.
      However, estimates of the total clearance (CL) of mAbs with linear clearance
      characteristics and of the clearance of mAbs via the linear clearance pathway
      (CL(L)) with parallel linear and nonlinear clearance were quite similar for the
      different mAbs and typically ranged from 0.2 to 0.5 L/day, which is relatively
      close to the estimated clearance of endogenous IgG of 0.21 L/day. The between
      subject variability in the V(max), CL and CL(L) was moderate to high, with
      estimated CVs ranging from 15% to 65%. Measures of body size were the covariates
      most commonly identified as influencing the pharmacokinetics of therapeutic mAbs.
      In summary, many features of the population pharmacokinetics of currently used
      therapeutic mAbs are similar, despite differences in their pharmacological
      targets and studied patient populations.

PMID- 20818832
TI  - A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and
      gabapentin.
AB  - Pregabalin and gabapentin share a similar mechanism of action, inhibiting calcium
      influx and subsequent release of excitatory neurotransmitters; however, the
      compounds differ in their pharmacokinetic and pharmacodynamic characteristics.
      Gabapentin is absorbed slowly after oral administration, with maximum plasma
      concentrations attained within 3-4 hours. Orally administered gabapentin exhibits
      saturable absorption--a nonlinear (zero-order) process--making its
      pharmacokinetics less predictable. Plasma concentrations of gabapentin do not
      increase proportionally with increasing dose. In contrast, orally administered
      pregabalin is absorbed more rapidly, with maximum plasma concentrations attained
      within 1 hour. Absorption is linear (first order), with plasma concentrations
      increasing proportionately with increasing dose. The absolute bioavailability of
      gabapentin drops from 60% to 33% as the dosage increases from 900 to 3600 mg/day,
      while the absolute bioavailability of pregabalin remains at > or = 90%
      irrespective of the dosage. Both drugs can be given without regard to meals.
      Neither drug binds to plasma proteins. Neither drug is metabolized by nor
      inhibits hepatic enzymes that are responsible for the metabolism of other drugs.
      Both drugs are excreted renally, with elimination half-lives of approximately 6
      hours. Pregabalin and gabapentin both show dose-response relationships in the
      treatment of postherpetic neuralgia and partial seizures. For neuropathic pain, a
      pregabalin dosage of 450 mg/day appears to reduce pain comparably to the
      predicted maximum effect of gabapentin. As an antiepileptic, pregabalin may be
      more effective than gabapentin, on the basis of the magnitude of the reduction in
      the seizure frequency. In conclusion, pregabalin appears to have some distinct
      pharmacokinetic advantages over gabapentin that may translate into an improved
      pharmacodynamic effect.

PMID- 20818833
TI  - Population pharmacokinetics of tapentadol immediate release (IR) in healthy
      subjects and patients with moderate or severe pain.
AB  - BACKGROUND: Tapentadol is a new, centrally active analgesic agent with two modes
      of action--mu opioid receptor agonism and norepinephrine reuptake inhibition--and
      the immediate-release (IR) formulation is approved in the US for the relief of
      moderate to severe acute pain. The aims of this analysis were to develop a
      population pharmacokinetic model to facilitate the understanding of the
      pharmacokinetics of tapentadol IR in healthy subjects and patients following
      single and multiple dosing, and to identify covariates that might explain
      variability in exposure following oral administration. METHODS: The analysis
      included pooled data from 11,385 serum pharmacokinetic samples from 1827 healthy
      subjects and patients with moderate to severe pain. Population pharmacokinetic
      modelling was conducted using nonlinear mixed-effects modelling (NONMEM) software
      to estimate population pharmacokinetic parameters and the influence of the
      subjects' demographic characteristics, clinical laboratory chemistry values and
      disease status on these parameters. Simulations were performed to assess the
      clinical relevance of the covariate effects on tapentadol exposure. RESULTS: A
      two-compartment model with zero-order release followed by first-order absorption
      and first-order elimination best described the pharmacokinetics of tapentadol IR
      following oral administration. The interindividual variability (coefficient of
      variation) in apparent oral clearance (CL/F) and the apparent central volume of
      distribution after oral administration were 30% and 29%, respectively. An
      additive error model was used to describe the residual variability in the log
      transformed data, and the standard deviation values were 0.308 and 0.314 for
      intensively and sparsely sampled data, respectively. Covariate analysis showed
      that sex, age, bodyweight, race, body fat, hepatic function (using total
      bilirubin and total protein as surrogate markers), health status and creatinine
      clearance were statistically significant factors influencing the pharmacokinetics
      of tapentadol. Total bilirubin was a particularly important factor that
      influenced CL/F, which decreased by more than 60% in subjects with total
      bilirubin greater than 50 micromol/L. CONCLUSIONS: The population pharmacokinetic
      model for tapentadol IR identified the relationship between pharmacokinetic
      parameters and a wide range of covariates. The simulations of tapentadol exposure
      with identified, statistically significant covariates demonstrated that only
      hepatic function (as characterized by total bilirubin and total protein) may be
      considered a clinically relevant factor that warrants dose adjustment. None of
      the other covariates are of clinical relevance, nor do they necessitate dose
      adjustment.

PMID- 20818834
TI  - Population pharmacokinetics and Bayesian estimation of tacrolimus exposure in
      renal transplant recipients on a new once-daily formulation.
AB  - BACKGROUND AND OBJECTIVES: Advagraf is a new extended-release once-daily
      formulation of tacrolimus, a potent immunosuppressant widely used in renal
      transplantation. The aims of his study were (i) to develop a population
      pharmacokinetic model for once-daily tacrolimus in adult renal transplant
      patients; and (ii) to develop a Bayesian estimator able to reliably estimate
      individual pharmacokinetic parameters and exposure indices. METHODS: Full
      pharmacokinetic profiles obtained from 41 adult renal transplant patients who had
      been switched from ciclosporin to a single daily dose of the new once-daily
      tacrolimus formulation for more than 6 months were analysed. Tacrolimus
      concentrations were measured using validated turbulent flow chromatography-tandem
      mass spectrometry methods. Population parameters were computed using nonlinear
      mixed-effect modelling software (NONMEM Version VI). The patients were randomly
      divided into (i) a model-building test group (n = 29); and (ii) a validation
      group (n = 12). Population pharmacokinetic analysis was performed to estimate the
      effects on tacrolimus pharmacokinetics of demographic characteristics (sex,
      bodyweight, age), drug interaction with prednisolone, laboratory test results
      (the haematocrit, haemaglobin level and serum creatinine level) and cytochrome
      P450 (CYP) 3A5 (CYP3A5) genetic polymorphism. The population pharmacokinetic
      model was further refined by taking into account all of the data from the 41
      patients, and the final model was validated using a bootstrap and a visual
      predictive check. For Bayesian estimation, the best limited-sampling strategy was
      determined on the basis of the D-optimality criterion and validation performed in
      the validation group. RESULTS: The trapezoidal area under the whole-blood
      concentration time curve from 0 to 24 hours (AUC(24)) of tacrolimus varied by up
      to 50% for the same trough concentration value. The pharmacokinetics of once
      daily tacrolimus were well described by a two-compartment model combined with an
      Erlang distribution to describe the absorption phase. The CYP3A5 genotype was the
      only covariate retained in the final model. The apparent clearance of tacrolimus
      was 2-fold higher in expressers (with the CYP3A5*1/*1 and CYP3A5*1/*3 genotypes)
      than in non-expressers (with the CYP3A5*3/*3 genotype). This factor explained
      around 25% of the interindividual variability in the apparent clearance. A
      posteriori Bayesian estimation allowed accurate prediction of the AUC(24) of once
      daily tacrolimus, using just three sampling times (0, 1 and 3 hours post-dose)
      with a nonsignificant mean bias of 0.7% (range 16-20%) and good precision (root
      mean square error 9%). CONCLUSIONS: Population pharmacokinetic analysis of once
      daily tacrolimus in renal transplant recipients resulted in identification of the
      CYP3A5*1/*3 genotype as a significant covariate on the apparent clearance of
      tacrolimus, and the design of an accurate maximum a posteriori Bayesian estimator
      based on three blood concentration measurements and this covariate. Such a tool
      could be helpful for comparing different exposure indices or different target
      levels. It could contribute to improvement of the efficacy and tolerability of
      once-daily tacrolimus in some patients.

PMID- 20818835
TI  - Development of a population pharmacokinetic model for atorvastatin acid and its
      lactone metabolite.
AB  - BACKGROUND AND OBJECTIVES: Atorvastatin lactone, a metabolite of the HMG-CoA
      reductase inhibitor (statin) atorvastatin acid, is believed to be myotoxic. Our
      objectives were to develop a population pharmacokinetic model for atorvastatin
      acid and its lactone metabolite and to identify patient characteristics that are
      predictive of variability in the pharmacokinetic parameters of the parent drug
      and its lactone metabolite. SUBJECTS AND METHODS: Twenty-six subjects, 13 of whom
      had experienced atorvastatin-induced myopathy, received atorvastatin 10 mg once
      daily for 7 days. Plasma samples taken on day 7 at 0 hours (predose) and 0.5, 1,
      1.5, 2, 3, 5, 7, 9, 12, 22 and 24 hours post-dose were analysed for both
      atorvastatin acid and atorvastatin lactone, using a validated liquid
      chromatography assay with tandem mass spectrometry, and the data were modelled
      using nonlinear mixed-effects modelling software (NONMEM). The influence of the
      patients' demographic characteristics, biochemical indices and pharmacogenomics
      was evaluated. Final model validation was carried out using a visual predictive
      check. RESULTS: The pharmacokinetics of atorvastatin acid and atorvastatin
      lactone were best described by two- and one-compartment models, respectively. The
      main pharmacokinetic parameters of atorvastatin acid (mean [relative standard
      error {RSE}]) for a subject with mean covariate values were the first-order
      absorption rate constant (3.5 h-1 fixed); oral clearance (504 L/h [29%]);
      apparent volume of the central compartment (3250 L [16.5%]); and apparent volume
      of the peripheral compartment (2170 L [9.3%]). The main pharmacokinetic
      parameters of atorvastatin lactone (mean [RSE]) were the apparent clearance to
      atorvastatin acid (24 L/h [154%]); apparent total body clearance (116 L/h
      [9.5%]); and apparent volume of distribution (137 L [33.7%]). The value of
      aspartate transaminase was identified as a significant covariate for the apparent
      volume of the central compartment for atorvastatin acid and for the apparent
      total body clearance of atorvastatin lactone, signifying the importance of liver
      function in atorvastatin pharmacokinetics. The visual predictive plots
      demonstrated that the model adequately described the pharmacokinetics of both
      species. CONCLUSION: A population pharmacokinetics model was developed and
      validated to describe atorvastatin acid and its lactone metabolite concentration
      time data. This model may be useful for atorvastatin dose individualization or
      analysis of sparse data.

PMID- 20818836
TI  - The placebo response: relationship to outcomes in trials of postherpetic
      neuralgia.
AB  - Placebo responses in controlled studies of neuropathic pain, including
      postherpetic neuralgia, have increased in recent years and may obscure benefits
      of potential treatments. Investigations of the basis of the placebo effect have
      revealed some of the anatomical and physiological substrates for these responses.
      Placebo responses are accompanied by changes in activity in brain regions
      involved in analgesia, pain processing, reward and emotion, and they involve
      neurotransmitters with well established roles in pain modulation, including
      opioids and cholecystokinin. These findings may eventually provide useful
      suggestions for limiting placebo responses in clinical trials as identification
      of the cues that contribute to placebo responses could conceivably permit their
      avoidance in the design of clinical studies. Analyses of the characteristics of
      clinical trials in neuropathic pain have revealed some factors that might also
      help explain the increase in placebo responses. These factors include the longer
      duration of contemporary trials and recruitment practices of high-enrolling study
      centres. In trials of patients with postherpetic neuralgia, inclusion of patients
      with a short duration of post-zoster pain can result in a high rate of
      spontaneous remission that can contribute to an apparent 'placebo response'.
      Future placebo-controlled trials of treatments for postherpetic neuralgia may
      need to consider modifications of the design and conduct of these studies to
      maximize the chance of obtaining valid study results.

PMID- 20818837
TI  - Attitudes, awareness, compliance and preferences among hormonal contraception
      users: a global, cross-sectional, self-administered, online survey.
AB  - BACKGROUND: Healthcare professionals have a responsibility to help each woman
      select the most appropriate hormonal contraceptive according to her personal
      preferences, needs and circumstances. OBJECTIVE: To assess attitudes, awareness,
      compliance and preferences of hormonal contraceptive users. STUDY DESIGN: A cross
      sectional survey conducted through self-administered, online questionnaires. One
      questionnaire was administered in the US and another was administered in the UK,
      France, Germany, Spain, Italy, Brazil, Australia and Russia (Eight-Country Survey
      questionnaire). PARTICIPANTS: Current hormonal contraceptive users, aged 18-44
      years, in the general community. RESULTS: Questionnaires were completed by 5120
      women. The mean age of the respondents was approximately 31 years and over 70%
      were current contraceptive pill users. Many women did not plan on having children
      in the next 3 years (range 44% in Russia to 77% in the US and UK), but a quick
      return of fertility upon contraceptive discontinuation was desired by the
      majority of women in all countries (range 54% in the US to 91% in Russia). Rates
      of discontinuation or switching to a different hormonal contraceptive in the past
      year ranged from 30% in Germany to 81% in Brazil. Requests to switch because of
      side effects ranged from 24% in Spain to 57% in Brazil. Results from the Eight
      Country Survey questionnaire indicated that 42% of women would consider using one
      of the most effective contraceptive methods even if their menstrual cycle
      changed, 58% would accept irregular bleeding initially if they had fewer periods
      over time, 53% did not want/had concerns about foreign/additional estrogen in
      their body, 85% would prefer a monthly option with a lower hormone dose over a
      daily pill, 80% would consider switching contraceptives to minimize estrogen
      exposure and 74% would prefer an estrogen-free/progestin (progesterone congener)
      only pill to avoid potential side effects from foreign/extra estrogen. Oral
      contraceptive users across all countries admitted missing (range 39% in the UK to
      65% in Brazil) or taking a pill at the wrong time (range 12% in Spain to 67% in
      Brazil) in the previous 3 months. Approximately 81% of all respondents said they
      would consider using a method that did not require daily, weekly or monthly
      dosing. The proportion of women believing themselves well informed about their
      contraception options ranged from 30% in Russia to 86% in the US. Informed women
      were generally more aware of alternative methods than their uninformed
      counterparts. Responses also varied significantly among women in different age
      groups. CONCLUSION: These findings demonstrate that a range of factors influence
      a woman's choice of contraceptive. This highlights the importance of
      individualized counselling during contraceptive selection to ensure that the
      option recommended is tailored to the personal preferences of each woman to
      improve compliance, continuance and prevention of an unwanted pregnancy.

PMID- 20818838
TI  - Gabapentin extended-release tablets for the treatment of patients with
      postherpetic neuralgia: a randomized, double-blind, placebo-controlled,
      multicentre study.
AB  - BACKGROUND: Postherpetic neuralgia (PHN) is a neuropathic pain syndrome that may
      develop subsequent to healing of herpes zoster rash. OBJECTIVES: This study aimed
      to determine the efficacy and safety of gabapentin extended-release (gabapentin
      ER) tablets for the treatment of patients with PHN and to determine whether
      optimal benefits might be achieved with once-daily (QD) or divided-dose (DD)
      administration. METHODS: This was a 10-week, randomized, double-blind, placebo
      controlled, multicentre trial comparing gabapentin ER (total daily dose 1800 mg)
      either QD or as an asymmetrical DD with placebo in 407 patients with post-zoster
      pain for >or=3 months and a baseline average daily pain score (ADP)>or=4 on a 0
      10 Likert numerical rating scale. The primary efficacy outcome was the ADP score
      mean change from baseline to week 10 using baseline observation carried forward
      (BOCF). Secondary efficacy outcomes included changes to week 10 in last
      observation carried forward (LOCF) ADP score, LOCF average daily sleep
      interference score, Short-Form McGill Pain Questionnaire score, Neuropathic Pain
      Scale score, and Brief Pain Inventory score. RESULTS: Of 407 randomized patients,
      400 were included in the intent-to-treat population (gabapentin ER QD, n=134;
      gabapentin ER DD, n=135; placebo, n=131). Between-group differences in the least
      squares (LS) mean changes in BOCF ADP scores did not reach statistical
      significance (gabapentin ER QD -1.85 [p=0.110 vs placebo]; gabapentin ER DD -1.72
      [p=0.255 vs placebo]; placebo -1.42). In the LOCF analysis, the LS mean ADP score
      for the gabapentin ER QD group, but not for the DD group, improved compared with
      placebo (gabapentin ER QD, -2.28; p=0.032 vs placebo). Improvements compared with
      placebo were also observed in the gabapentin ER QD group, but not for the DD
      group, for mean daily sleep interference scores (gabapentin ER QD, -2.49;
      placebo, -1.63; p<0.001). Most adverse events (AEs) were mild or moderate. Among
      gabapentin-treated patients, 12% and 11% withdrew due to AEs, most commonly for
      dizziness (2% and 3%), in the gabapentin ER QD and DD groups, respectively.
      Treatment-related AEs in the gabapentin ER-treated groups occurred in 31% of
      patients. The most common AEs in the gabapentin ER QD and DD groups included
      dizziness (10% and 15%), headache (4% and 7%), somnolence (3% and 7%) and
      peripheral oedema (5% and 5%), respectively. CONCLUSION: The primary efficacy
      endpoint for this study of gabapentin ER was not met, most likely due to the
      unexpectedly large placebo response. Outcomes on secondary endpoints suggest the
      potential efficacy of gabapentin ER QD. Gabapentin ER was well tolerated in this
      study. [Clinicaltrials.gov identifier NCT00335933].

PMID- 20818839
TI  - Treatment of advanced Parkinson's disease in the United States: a cost-utility
      model.
AB  - BACKGROUND: As Parkinson's disease (PD) progresses, patients and their families
      experience substantial health and economic burdens. Because motor fluctuations
      (also called 'off-time') are linked to poor quality of life and higher healthcare
      costs, minimizing off-time is an effective strategy for reducing costs associated
      with PD. OBJECTIVE: To assess the cost utility of rasagiline or entacapone as
      adjunctive therapies to levodopa versus levodopa/carbidopa/entacapone (LCE)
      versus standard levodopa monotherapy in patients with advanced PD and motor
      fluctuations in the US. METHODS: A 2-year stochastic Markov model was utilized to
      examine the cost effectiveness of treatments of advanced PD. The model assumed
      that patients transition health status every 4 months. Transition probabilities,
      including uncertainties, were estimated from clinical trial data. Medical costs,
      daily drug costs and utility weights were obtained from published literature.
      RESULTS: Over 2 years, all therapy options showed greater effectiveness than
      levodopa alone. Rasagiline+levodopa and LCE were cost saving from a payor
      perspective, while entacapone+levodopa was cost saving from a societal
      perspective. Mean benefits over 2 years were 0.12 (90% credibility interval [CI]
      0.07, 0.18) additional quality-adjusted life-years (QALYs) for
      rasagiline+levodopa, entacapone+levodopa and LCE, 5.08 (90% CI 3.87, 6.28)
      additional months with <or=25% off-time for rasagiline+levodopa and 4.85 (90% CI
      3.63, 6.06) additional months with <or=25% off-time for entacapone+levodopa and
      LCE versus levodopa alone. CONCLUSION: From a payor perspective,
      rasagiline+levodopa and LCE were dominant therapies over levodopa monotherapy,
      while entacapone+levodopa was effective at a higher cost. With no additional cost
      over a 2-year period, rasagiline+levodopa presents a valuable alternative to
      entacapone+levodopa, LCE and levodopa monotherapy in the treatment of advanced PD
      patients. Results from this cost-utility model and prior adjunctive clinical data
      provide ongoing support for the adjunctive use of rasagiline in advanced PD
      patients with motor fluctuations.

PMID- 20818840
TI  - Maternal smoking at first prenatal visit as a marker of risk for adverse
      pregnancy outcomes in the Qikiqtaaluk (Baffin) Region.
AB  - INTRODUCTION: In Nunavut, 60-80% of pregnant women report smoking in pregnancy, a
      rate five times the Canadian average. Nunavut also has the highest rates of
      preterm birth and low birth weight infants in Canada. The present study assessed
      whether the number of cigarettes smoked per day, as recorded in the first
      trimester, influenced birth outcomes. METHODS: Maternal-newborn charts were
      reviewed for infants born between 1 January 2003 and 31 December 2005 to at least
      one Inuit parent in the Qikiqtaaluk (Baffin) region of Nunavut. Smoking data, as
      reported by the mother at an early prenatal visit, were extracted from the
      prenatal record. Birth outcomes including birth weights (for term births), low
      birth weight, small for gestational age births and rates of preterm birth, were
      analysed according to category of reported number of cigarettes smoked (0, 1-5, 6
      10, and >10 per day). Maternal age, alcohol and street drug use were also
      assessed for each category of smokers. Statistical analysis among groups was
      carried out. RESULTS: Of 918 births meeting the study criteria, more than 80% of
      women reported smoking. For 80% of those, the amount smoked per day was
      available. Non-smokers and women smoking less than 5 cigarettes daily had
      perinatal outcomes equal to or better than Canadian averages for low birth
      weight, small for gestational age, and preterm birth. Furthermore, average birth
      weights at term significantly decreased from 3681 g for non smokers to 3310 g for
      those smoking more than 10 cigarettes per day. Compared with non-smokers, women
      in the highest smoking category (>10 cigarettes daily) had a six-fold increase in
      low birth weight infants (OR 6.7, 95% CI 2.3-19.6), almost a four-fold increase
      for small for gestational age births (OR 3.7, 95% CI 1.6-8.8) and twice the
      chance of a premature birth compared with non-smokers (OR 2.14, 95% CI 1.1-4.2).
      Those in the highest smoking category were also most likely to report alcohol and
      other substance use. CONCLUSIONS: Inuit women who reported not smoking, or
      smoking less than 5 cigarettes per day had birth outcomes equal or superior to
      average Canadian outcomes in each category evaluated. Those women reporting
      smoking more than 10 cigarettes daily had significantly increased risk for
      preterm birth, low birth weight and small for gestational age infants. Because
      those in the highest smoking category also reported the highest rates of alcohol
      and other substance use, it is likely that a combination of factors assessed in
      this study influenced the outcomes. Along with public health preventative
      measures to reduce smoking directed to this high risk group, other contributing
      factors for adverse birth outcomes need to be assessed more fully to understand
      the complex interactions that lead to increased smoking, substance use and,
      therefore, adverse birth outcomes. Furthermore, evidence from this study suggests
      that smoking more than 10 cigarettes per day, reported at first prenatal visit,
      may provide a marker for those women at highest risk of poor outcomes, which
      could provide direction for focused public health efforts.

PMID- 20818841
TI  - A multi-university evaluation of the rural clinical school experience of
      Australian medical students.
AB  - INTRODUCTION: Medical students have been attending rural clinical schools (RCSs)
      since 2001. Although there have been generally positive single institution
      reports, there has been no multi-institution study using a common survey
      instrument. The experiences of medical students who attended a number of RCSs
      during 2006 were evaluated using a rural-specific questionnaire. METHODS:
      Questionnaires were distributed to 166 medical students who had completed one
      year at the RCS of six participating universities across Australia, including the
      Universities of New South Wales, Melbourne, Tasmania, Adelaide, and Sydney, and
      the Australian National University, of whom 125 responded (75.3%). Students were
      asked to rate their level of agreement on 29 items concerning their overall RCS
      experience, skills development and clinical supervision experience. RESULTS: The
      majority of respondents (n = 107, 86%) stated they would go to the RCS again if
      they had their time over and almost two-thirds (n = 77, 64%) stated they would
      spend more time at the RCS if they could. All items evaluating the educational
      experience recorded greater than 80% agreement (indicating very positive
      perceptions of the RCS experience). For the items concerning skills development,
      the highest level of agreement related to developing procedural skills (n = 121,
      97%). For items relating to clinical supervision the agreement rate exceeded 80%.
      The majority of students found supervisors approachable (n = 121, 97%),
      enthusiastic (n = 120, 96%) and respectful (n = 119, 95%). CONCLUSIONS: Students'
      experiences in the RCSs are unequivocally positive. Most importantly, the RCS
      environment was conducive to learning and the development of clinical skills, the
      students were able to see an adequate number of patients and were well-prepared
      for examinations, and their supervisors were very good and acted as positive role
      models. This augers well for the success of the RCS program and for its role in
      attracting future doctors to work in rural environments.

PMID- 20818842
TI  - 'Even if we get one back here, it's worth it...': evaluation of an Australian
      Remote Area Health Placement Program.
AB  - INTRODUCTION: In 2006 the Kimberley Remote Area Health Placement Program
      (hereinafter the 'Program') was established at the University of Notre Dame's
      School of Medicine (Fremantle campus, Western Australia). The Program was
      developed as one of the strategies to achieve the School of Medicine's mission to
      graduate knowledgeable, skillful, dutiful and ethical doctors who will want to
      work in Australian areas of unmet need. The Program aims to immerse medical
      students in non-clinical settings to provide them with opportunities to learn
      life skills required for remote area living, and to introduce them to the myriad
      of socio-cultural, geographic, climatic and economic factors that impact on the
      health and wellbeing of remote area residents. To meet these objectives, the
      School organizes for students to live with, and do useful non-clinical work for,
      a host community or organization for up to one week. In 2008 the Program was
      evaluated to explore and assess its immediate and potential future benefits and
      limitations as perceived by Kimberley residents. This paper reports on the
      evaluation's findings via Kimberley-based narratives and raises some issues that
      are essential to training and retaining a 'bloody good doctor...' in a remote
      Australian setting. METHODS: Using a mix of qualitative, ethnographic methods,
      the Program was evaluated by an independent researcher during four weeks of field
      research in late 2008. The methods included a survey, structured and unstructured
      interviewing and participant observation to elicit data. Thirty-three formal
      interviews of at least one hour's duration were conducted. Data were also
      collected via 15 informal discussions. Both formal and conservational
      interactions occurred in a range of town-based and more remote settings. RESULTS:
      The majority of persons consulted generally highlighted the Program's benefits.
      The reasons for this positive evaluation varied, but a common thread was that
      exposure to the Kimberley introduced the students to local life, a quality that
      had the potential to result in a medical student returning as a qualified doctor.
      The Program was seen as beneficial because it provided a structured, constructive
      means for prospective doctors to appreciate the assets rather than the deficits
      of remote area living. Another positive implication was that the Program equipped
      future doctors (regardless of their eventual work location) to treat a person
      from the 'bush'. It also encouraged students to think and act cross-culturally.
      An important immediate benefit was that the Program offered human resource
      support to the host organization at a busy time of the year. In only three of the
      33 formal interviews was a negative or ambivalent attitude toward the Program
      expressed. However, a common concern was the brevity of time students served with
      their host organization. CONCLUSIONS: The data collected revealed that Kimberley
      people believed that the Program held strong potential for the successful
      recruitment of doctors prepared to make a long-term commitment to the region.
      Never far from their minds, conversations and activities was the idea that the
      effort they put into accommodating, supporting and guiding the students was worth
      it because 'If only one good doctor comes from the Program, then that's a good
      thing. A good doctor would have a great impact - the implications are
      immeasurable...'.

PMID- 20818843
TI  - Can we treat cancer for a dollar a day? Guidelines for low-income countries.

PMID- 20818844
TI  - Inhibition of mutated, activated BRAF in metastatic melanoma.
AB  - BACKGROUND: The identification of somatic mutations in the gene encoding the
      serine-threonine protein kinase B-RAF (BRAF) in the majority of melanomas offers
      an opportunity to test oncogene-targeted therapy for this disease. METHODS: We
      conducted a multicenter, phase 1, dose-escalation trial of PLX4032 (also known as
      RG7204), an orally available inhibitor of mutated BRAF, followed by an extension
      phase involving the maximum dose that could be administered without adverse
      effects (the recommended phase 2 dose). Patients received PLX4032 twice daily
      until they had disease progression. Pharmacokinetic analysis and tumor-response
      assessments were conducted in all patients. In selected patients, tumor biopsy
      was performed before and during treatment to validate BRAF inhibition. RESULTS: A
      total of 55 patients (49 of whom had melanoma) were enrolled in the dose
      escalation phase, and 32 additional patients with metastatic melanoma who had
      BRAF with the V600E mutation were enrolled in the extension phase. The
      recommended phase 2 dose was 960 mg twice daily, with increases in the dose
      limited by grade 2 or 3 rash, fatigue, and arthralgia. In the dose-escalation
      cohort, among the 16 patients with melanoma whose tumors carried the V600E BRAF
      mutation and who were receiving 240 mg or more of PLX4032 twice daily, 10 had a
      partial response and 1 had a complete response. Among the 32 patients in the
      extension cohort, 24 had a partial response and 2 had a complete response. The
      estimated median progression-free survival among all patients was more than 7
      months. CONCLUSIONS: Treatment of metastatic melanoma with PLX4032 in patients
      with tumors that carry the V600E BRAF mutation resulted in complete or partial
      tumor regression in the majority of patients. (Funded by Plexxikon and Roche
      Pharmaceuticals.)

PMID- 20818845
TI  - Underinsurance among children in the United States.
AB  - BACKGROUND: Recent interest in policy regarding children's health insurance has
      focused on expanding coverage. Less attention has been devoted to the question of
      whether insurance sufficiently meets children's needs. METHODS: We estimated
      underinsurance among U.S. children on the basis of data from the 2007 National
      Survey of Children's Health (sample size, 91,642 children) regarding parents' or
      guardians' judgments of whether their children's insurance covered needed
      services and providers and reasonably covered costs. Data on adequacy were
      combined with data on continuity of insurance coverage to classify children as
      never insured during the past year, sometimes insured during the past year,
      continuously insured but inadequately covered (i.e., underinsured), and
      continuously insured and adequately covered. We examined the association between
      this classification and five overall indicators of health care access and
      quality: delayed or forgone care, difficulty obtaining needed care from a
      specialist, no preventive care, no developmental screening at a preventive visit,
      and care not meeting the criteria of a medical home. RESULTS: We estimated that
      in 2007, 11 million children were without health insurance for all or part of the
      year, and 22.7% of children with continuous insurance coverage--14.1 million
      children--were underinsured. Older children, Hispanic children, children in fair
      or poor health, and children with special health care needs were more likely to
      be underinsured. As compared with children who were continuously and adequately
      insured, uninsured and underinsured children were more likely to have problems
      with health care access and quality. CONCLUSIONS: The number of underinsured
      children exceeded the number of children without insurance for all or part of the
      year studied. Access to health care and the quality of health care are suboptimal
      for uninsured and underinsured children. (Funded by the Health Resources and
      Services Administration.)

PMID- 20818846
TI  - New therapeutic approaches to mendelian disorders.

PMID- 20818847
TI  - Images in clinical medicine. Liposarcoma of the anterior mediastinum and neck.

PMID- 20818848
TI  - Case records of the Massachusetts General Hospital. Case 26-2010. A 54-year-old
      man with loss of vision and a rash.

PMID- 20818849
TI  - Melanoma--an unlikely poster child for personalized cancer therapy.

PMID- 20818850
TI  - Treating underinsurance.

PMID- 20818851
TI  - Moving targets that drive cancer progression.

PMID- 20818852
TI  - Reference range for cerebrospinal fluid opening pressure in children.

PMID- 20818853
TI  - Quality measures and the individual physician.

PMID- 20818854
TI  - Bone marrow transplantation for recessive dystrophic epidermolysis bullosa.
AB  - BACKGROUND: Recessive dystrophic epidermolysis bullosa is an incurable, often
      fatal mucocutaneous blistering disease caused by mutations in COL7A1, the gene
      encoding type VII collagen (C7). On the basis of preclinical data showing
      biochemical correction and prolonged survival in col7 -/- mice, we hypothesized
      that allogeneic marrow contains stem cells capable of ameliorating the
      manifestations of recessive dystrophic epidermolysis bullosa in humans. METHODS:
      Between October 2007 and August 2009, we treated seven children who had recessive
      dystrophic epidermolysis bullosa with immunomyeloablative chemotherapy and
      allogeneic stem-cell transplantation. We assessed C7 expression by means of
      immunofluorescence staining and used transmission electron microscopy to
      visualize anchoring fibrils. We measured chimerism by means of competitive
      polymerase-chain-reaction assay, and documented blister formation and wound
      healing with the use of digital photography. RESULTS: One patient died of
      cardiomyopathy before transplantation. Of the remaining six patients, one had
      severe regimen-related cutaneous toxicity, with all having improved wound healing
      and a reduction in blister formation between 30 and 130 days after
      transplantation. We observed increased C7 deposition at the dermal-epidermal
      junction in five of the six recipients, albeit without normalization of anchoring
      fibrils. Five recipients were alive 130 to 799 days after transplantation; one
      died at 183 days as a consequence of graft rejection and infection. The six
      recipients had substantial proportions of donor cells in the skin, and none had
      detectable anti-C7 antibodies. CONCLUSIONS: Increased C7 deposition and a
      sustained presence of donor cells were found in the skin of children with
      recessive dystrophic epidermolysis bullosa after allogeneic bone marrow
      transplantation. Further studies are needed to assess the long-term risks and
      benefits of such therapy in patients with this disorder. (Funded by the National
      Institutes of Health; ClinicalTrials.gov number, NCT00478244.)

PMID- 20818856
TI  - Early-stage Hodgkin's lymphoma.

PMID- 20818855
TI  - Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma.
AB  - BACKGROUND: Whether it is possible to reduce the intensity of treatment in early
      (stage I or II) Hodgkin's lymphoma with a favorable prognosis remains unclear. We
      therefore conducted a multicenter, randomized trial comparing four treatment
      groups consisting of a combination chemotherapy regimen of two different
      intensities followed by involved-field radiation therapy at two different dose
      levels. METHODS: We randomly assigned 1370 patients with newly diagnosed early
      stage Hodgkin's lymphoma with a favorable prognosis to one of four treatment
      groups: four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine
      (ABVD) followed by 30 Gy of radiation therapy (group 1), four cycles of ABVD
      followed by 20 Gy of radiation therapy (group 2), two cycles of ABVD followed by
      30 Gy of radiation therapy (group 3), or two cycles of ABVD followed by 20 Gy of
      radiation therapy (group 4). The primary end point was freedom from treatment
      failure; secondary end points included efficacy and toxicity of treatment.
      RESULTS: The two chemotherapy regimens did not differ significantly with respect
      to freedom from treatment failure (P=0.39) or overall survival (P=0.61). At 5
      years, the rates of freedom from treatment failure were 93.0% (95% confidence
      interval [CI], 90.5 to 94.8) with the four-cycle ABVD regimen and 91.1% (95% CI,
      88.3 to 93.2) with the two-cycle regimen. When the effects of 20-Gy and 30-Gy
      doses of radiation therapy were compared, there were also no significant
      differences in freedom from treatment failure (P=1.00) or overall survival
      (P=0.61). Adverse events and acute toxic effects of treatment were most common in
      the patients who received four cycles of ABVD and 30 Gy of radiation therapy
      (group 1). CONCLUSIONS: In patients with early-stage Hodgkin's lymphoma and a
      favorable prognosis, treatment with two cycles of ABVD followed by 20 Gy of
      involved-field radiation therapy is as effective as, and less toxic than, four
      cycles of ABVD followed by 30 Gy of involved-field radiation therapy. Long-term
      effects of these treatments have not yet been fully assessed. (Funded by the
      Deutsche Krebshilfe and the Swiss Federal Government; ClinicalTrials.gov number,
      NCT00265018.)

PMID- 20818857
TI  - Images in clinical medicine. Retinal hemangioblastoma in von Hippel-Lindau
      disease.

PMID- 20818858
TI  - Case records of the Massachusetts General Hospital. Case 24-2010. A 56-year-old
      woman with a history of Hodgkin's lymphoma and sudden onset of dyspnea and shock.

PMID- 20818859
TI  - The New NEJM.org.
AB  - Each week, half a million readers access the Journal electronically, and our
      content is now seen online by about four times as many people as those who see
      the print edition. This mode of information delivery has expanded tremendously
      since the Journal first went online in 1996.(1) Not so long ago, electronic
      publishing was viewed as secondary to print publication, basically as a
      convenient way to deliver the print version of an article. Today, the electronic
      presentation of scientific articles has become the version of record, with print
      becoming only one part of the complete publication, which may include video, . .
      .

PMID- 20818860
TI  - Systemic therapy for a genetic skin disease.

PMID- 20818861
TI  - Sepsis and endothelial permeability.

PMID- 20818863
TI  - CPR with chest compression alone or with rescue breathing.
AB  - BACKGROUND: The role of rescue breathing in cardiopulmonary resuscitation (CPR)
      performed by a layperson is uncertain. We hypothesized that the dispatcher
      instructions to bystanders to provide chest compression alone would result in
      improved survival as compared with instructions to provide chest compression plus
      rescue breathing. METHODS: We conducted a multicenter, randomized trial of
      dispatcher instructions to bystanders for performing CPR. The patients were
      persons 18 years of age or older with out-of-hospital cardiac arrest for whom
      dispatchers initiated CPR instruction to bystanders. Patients were randomly
      assigned to receive chest compression alone or chest compression plus rescue
      breathing. The primary outcome was survival to hospital discharge. Secondary
      outcomes included a favorable neurologic outcome at discharge. RESULTS: Of the
      1941 patients who met the inclusion criteria, 981 were randomly assigned to
      receive chest compression alone and 960 to receive chest compression plus rescue
      breathing. We observed no significant difference between the two groups in the
      proportion of patients who survived to hospital discharge (12.5% with chest
      compression alone and 11.0% with chest compression plus rescue breathing, P=0.31)
      or in the proportion who survived with a favorable neurologic outcome in the two
      sites that assessed this secondary outcome (14.4% and 11.5%, respectively;
      P=0.13). Prespecified subgroup analyses showed a trend toward a higher proportion
      of patients surviving to hospital discharge with chest compression alone as
      compared with chest compression plus rescue breathing for patients with a cardiac
      cause of arrest (15.5% vs. 12.3%, P=0.09) and for those with shockable rhythms
      (31.9% vs. 25.7%, P=0.09). CONCLUSIONS: Dispatcher instruction consisting of
      chest compression alone did not increase the survival rate overall, although
      there was a trend toward better outcomes in key clinical subgroups. The results
      support a strategy for CPR performed by laypersons that emphasizes chest
      compression and minimizes the role of rescue breathing. (Funded in part by the
      Laerdal Foundation for Acute Medicine and the Medic One Foundation;
      ClinicalTrials.gov number, NCT00219687.)

PMID- 20818862
TI  - Sipuleucel-T immunotherapy for castration-resistant prostate cancer.
AB  - BACKGROUND: Sipuleucel-T, an autologous active cellular immunotherapy, has shown
      evidence of efficacy in reducing the risk of death among men with metastatic
      castration-resistant prostate cancer. METHODS: In this double-blind, placebo
      controlled, multicenter phase 3 trial, we randomly assigned 512 patients in a 2:1
      ratio to receive either sipuleucel-T (341 patients) or placebo (171 patients)
      administered intravenously every 2 weeks, for a total of three infusions. The
      primary end point was overall survival, analyzed by means of a stratified Cox
      regression model adjusted for baseline levels of serum prostate-specific antigen
      (PSA) and lactate dehydrogenase. RESULTS: In the sipuleucel-T group, there was a
      relative reduction of 22% in the risk of death as compared with the placebo group
      (hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P=0.03). This
      reduction represented a 4.1-month improvement in median survival (25.8 months in
      the sipuleucel-T group vs. 21.7 months in the placebo group). The 36-month
      survival probability was 31.7% in the sipuleucel-T group versus 23.0% in the
      placebo group. The treatment effect was also observed with the use of an
      unadjusted Cox model and a log-rank test (hazard ratio, 0.77; 95% CI, 0.61 to
      0.97; P=0.02) and after adjustment for use of docetaxel after the study therapy
      (hazard ratio, 0.78; 95% CI, 0.62 to 0.98; P=0.03). The time to objective disease
      progression was similar in the two study groups. Immune responses to the
      immunizing antigen were observed in patients who received sipuleucel-T. Adverse
      events that were more frequently reported in the sipuleucel-T group than in the
      placebo group included chills, fever, and headache. CONCLUSIONS: The use of
      sipuleucel-T prolonged overall survival among men with metastatic castration
      resistant prostate cancer. No effect on the time to disease progression was
      observed. (Funded by Dendreon; ClinicalTrials.gov number, NCT00065442.)

PMID- 20818864
TI  - Compression-only CPR or standard CPR in out-of-hospital cardiac arrest.
AB  - BACKGROUND: Emergency medical dispatchers give instructions on how to perform
      cardiopulmonary resuscitation (CPR) over the telephone to callers requesting help
      for a patient with suspected cardiac arrest, before the arrival of emergency
      medical services (EMS) personnel. A previous study indicated that instructions to
      perform CPR consisting of only chest compression result in a treatment efficacy
      that is similar or even superior to that associated with instructions given to
      perform standard CPR, which consists of both compression and ventilation. That
      study, however, was not powered to assess a possible difference in survival. The
      aim of this prospective, randomized study was to evaluate the possible
      superiority of compression-only CPR over standard CPR with respect to survival.
      METHODS: Patients with suspected, witnessed, out-of-hospital cardiac arrest were
      randomly assigned to undergo either compression-only CPR or standard CPR. The
      primary end point was 30-day survival. RESULTS: Data for the primary analysis
      were collected from February 2005 through January 2009 for a total of 1276
      patients. Of these, 620 patients had been assigned to receive compression-only
      CPR and 656 patients had been assigned to receive standard CPR. The rate of 30
      day survival was similar in the two groups: 8.7% (54 of 620 patients) in the
      group receiving compression-only CPR and 7.0% (46 of 656 patients) in the group
      receiving standard CPR (absolute difference for compression-only vs. standard
      CPR, 1.7 percentage points; 95% confidence interval, -1.2 to 4.6; P=0.29).
      CONCLUSIONS: This prospective, randomized study showed no significant difference
      with respect to survival at 30 days between instructions given by an emergency
      medical dispatcher, before the arrival of EMS personnel, for compression-only CPR
      and instructions for standard CPR in patients with suspected, witnessed, out-of
      hospital cardiac arrest. (Funded by the Swedish Heart-Lung Foundation and others;
      Karolinska Clinical Trial Registration number, CT20080012.)

PMID- 20818865
TI  - Acupuncture for chronic low back pain.

PMID- 20818866
TI  - Images in clinical medicine. Pneumothorax--an uncommon complication of a common
      procedure.

PMID- 20818867
TI  - Case records of the Massachusetts General Hospital. Case 23-2010. A 49-year-old
      man with erythrocytosis, perinephric fluid collections, and renal failure.

PMID- 20818868
TI  - New therapies for castration-resistant prostate cancer.

PMID- 20818869
TI  - In CPR, less may be better.

PMID- 20818870
TI  - Response to dengue fever--the good, the bad, and the ugly?

PMID- 20818871
TI  - PLA2R autoantibodies and recurrent membranous nephropathy after transplantation.

PMID- 20818872
TI  - New technology and health care costs--the case of robot-assisted surgery.

PMID- 20818873
TI  - New priorities for future biomedical innovations.

PMID- 20818874
TI  - Racial variation in medical outcomes among living kidney donors.
AB  - BACKGROUND: Data regarding health outcomes among living kidney donors are
      lacking, especially among nonwhite persons. METHODS: We linked identifiers from
      the Organ Procurement and Transplantation Network (OPTN) with administrative data
      of a private U.S. health insurer and performed a retrospective study of 4650
      persons who had been living kidney donors from October 1987 through July 2007 and
      who had post-donation nephrectomy benefits with this insurer at some point from
      2000 through 2007. We ascertained post-nephrectomy medical diagnoses and
      conditions requiring medical treatment from billing claims. Cox regression
      analyses with left and right censoring to account for observed periods of
      insurance benefits were used to estimate absolute prevalence and prevalence
      ratios for diagnoses after nephrectomy. We then compared prevalence patterns with
      those in the 2005-2006 National Health and Nutrition Examination Survey (NHANES)
      for the general population. RESULTS: Among the donors, 76.3% were white, 13.1%
      black, 8.2% Hispanic, and 2.4% another race or ethnic group. The median time from
      donation to the end of insurance benefits was 7.7 years. After kidney donation,
      black donors, as compared with white donors, had an increased risk of
      hypertension (adjusted hazard ratio, 1.52; 95% confidence interval [CI], 1.23 to
      1.88), diabetes mellitus requiring drug therapy (adjusted hazard ratio, 2.31; 95%
      CI, 1.33 to 3.98), and chronic kidney disease (adjusted hazard ratio, 2.32; 95%
      CI, 1.48 to 3.62); findings were similar for Hispanic donors. The absolute
      prevalence of diabetes among all donors did not exceed that in the general
      population, but the prevalence of hypertension exceeded NHANES estimates in some
      subgroups. End-stage renal disease was identified in less than 1% of donors but
      was more common among black donors than among white donors. CONCLUSIONS: As in
      the general U.S. population, racial disparities in medical conditions occur among
      living kidney donors. Increased attention to health outcomes among
      demographically diverse kidney donors is needed. (Funded by the National
      Institute of Diabetes and Digestive and Kidney Diseases and others.)

PMID- 20818875
TI  - Early palliative care for patients with metastatic non-small-cell lung cancer.
AB  - BACKGROUND: Patients with metastatic non-small-cell lung cancer have a
      substantial symptom burden and may receive aggressive care at the end of life. We
      examined the effect of introducing palliative care early after diagnosis on
      patient-reported outcomes and end-of-life care among ambulatory patients with
      newly diagnosed disease. METHODS: We randomly assigned patients with newly
      diagnosed metastatic non-small-cell lung cancer to receive either early
      palliative care integrated with standard oncologic care or standard oncologic
      care alone. Quality of life and mood were assessed at baseline and at 12 weeks
      with the use of the Functional Assessment of Cancer Therapy-Lung (FACT-L) scale
      and the Hospital Anxiety and Depression Scale, respectively. The primary outcome
      was the change in the quality of life at 12 weeks. Data on end-of-life care were
      collected from electronic medical records. RESULTS: Of the 151 patients who
      underwent randomization, 27 died by 12 weeks and 107 (86% of the remaining
      patients) completed assessments. Patients assigned to early palliative care had a
      better quality of life than did patients assigned to standard care (mean score on
      the FACT-L scale [in which scores range from 0 to 136, with higher scores
      indicating better quality of life], 98.0 vs. 91.5; P=0.03). In addition, fewer
      patients in the palliative care group than in the standard care group had
      depressive symptoms (16% vs. 38%, P=0.01). Despite the fact that fewer patients
      in the early palliative care group than in the standard care group received
      aggressive end-of-life care (33% vs. 54%, P=0.05), median survival was longer
      among patients receiving early palliative care (11.6 months vs. 8.9 months,
      P=0.02). CONCLUSIONS: Among patients with metastatic non-small-cell lung cancer,
      early palliative care led to significant improvements in both quality of life and
      mood. As compared with patients receiving standard care, patients receiving early
      palliative care had less aggressive care at the end of life but longer survival.
      (Funded by an American Society of Clinical Oncology Career Development Award and
      philanthropic gifts; ClinicalTrials.gov number, NCT01038271.)

PMID- 20818876
TI  - A randomized trial of tai chi for fibromyalgia.
AB  - BACKGROUND: Previous research has suggested that tai chi offers a therapeutic
      benefit in patients with fibromyalgia. METHODS: We conducted a single-blind,
      randomized trial of classic Yang-style tai chi as compared with a control
      intervention consisting of wellness education and stretching for the treatment of
      fibromyalgia (defined by American College of Rheumatology 1990 criteria).
      Sessions lasted 60 minutes each and took place twice a week for 12 weeks for each
      of the study groups. The primary end point was a change in the Fibromyalgia
      Impact Questionnaire (FIQ) score (ranging from 0 to 100, with higher scores
      indicating more severe symptoms) at the end of 12 weeks. Secondary end points
      included summary scores on the physical and mental components of the Medical
      Outcomes Study 36-Item Short-Form Health Survey (SF-36). All assessments were
      repeated at 24 weeks to test the durability of the response. RESULTS: Of the 66
      randomly assigned patients, the 33 in the tai chi group had clinically important
      improvements in the FIQ total score and quality of life. Mean (+/-SD) baseline
      and 12-week FIQ scores for the tai chi group were 62.9+/-15.5 and 35.1+/-18.8,
      respectively, versus 68.0+/-11 and 58.6+/-17.6, respectively, for the control
      group (change from baseline in the tai chi group vs. change from baseline in the
      control group, -18.4 points; P<0.001). The corresponding SF-36 physical-component
      scores were 28.5+/-8.4 and 37.0+/-10.5 for the tai chi group versus 28.0+/-7.8
      and 29.4+/-7.4 for the control group (between-group difference, 7.1 points;
      P=0.001), and the mental-component scores were 42.6+/-12.2 and 50.3+/-10.2 for
      the tai chi group versus 37.8+/-10.5 and 39.4+/-11.9 for the control group
      (between-group difference, 6.1 points; P=0.03). Improvements were maintained at
      24 weeks (between-group difference in the FIQ score, -18.3 points; P<0.001). No
      adverse events were observed. CONCLUSIONS: Tai chi may be a useful treatment for
      fibromyalgia and merits long-term study in larger study populations. (Funded by
      the National Center for Complementary and Alternative Medicine and others;
      ClinicalTrials.gov number, NCT00515008.)

PMID- 20818877
TI  - Clinical practice. Emergency treatment of asthma.

PMID- 20818878
TI  - Images in clinical medicine. Acute optic-nerve infarction in carotid dissection.

PMID- 20818879
TI  - Case records of the Massachusetts General Hospital. Case 25-2010. A 24-year-old
      woman with abdominal pain and shock.

PMID- 20818880
TI  - Treating cancer by targeting the immune system.

PMID- 20818881
TI  - Palliative care--a shifting paradigm.

PMID- 20818882
TI  - Prescribing tai chi for fibromyalgia--are we there yet?

PMID- 20818883
TI  - HPV vaccination mandates--lawmaking amid political and scientific controversy.

PMID- 20818884
TI  - Mortality among living kidney donors and comparison populations.

PMID- 20818886
TI  - Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema.
AB  - BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency is characterized
      by recurrent acute attacks of swelling that can be painful and sometimes life
      threatening. METHODS: We conducted two randomized trials to evaluate nanofiltered
      C1 inhibitor concentrate in the management of hereditary angioedema. The first
      study compared nanofiltered C1 inhibitor concentrate with placebo for treatment
      of an acute attack of angioedema. A total of 68 subjects (35 in the C1 inhibitor
      group and 33 in the placebo group) were given one or two intravenous injections
      of the study drug (1000 units each). The primary end point was the time to the
      onset of unequivocal relief. The second study was a crossover trial involving 22
      subjects with hereditary angioedema that compared prophylactic twice-weekly
      injections of nanofiltered C1 inhibitor concentrate (1000 units) with placebo
      during two 12-week periods. The primary end point was the number of attacks of
      angioedema per period, with each subject acting as his or her own control.
      RESULTS: In the first study, the median time to the onset of unequivocal relief
      from an attack was 2 hours in the subjects treated with C1 inhibitor concentrate
      but longer than 4 hours in those given placebo (P=0.02). In the second study, the
      number of attacks per 12-week period was 6.26 with C1 inhibitor concentrate given
      as prophylaxis, as compared with 12.73 with placebo (P<0.001); the subjects who
      received the C1 inhibitor concentrate also had significant reductions in both the
      severity and the duration of attacks, in the need for open-label rescue therapy,
      and in the total number of days with swelling. CONCLUSIONS: In subjects with
      hereditary angioedema, nanofiltered C1 inhibitor concentrate shortened the
      duration of acute attacks. When used for prophylaxis, nanofiltered C1 inhibitor
      concentrate reduced the frequency of acute attacks. (Funded by Lev
      Pharmaceuticals; ClinicalTrials.gov numbers, NCT00289211, NCT01005888,
      NCT00438815, and NCT00462709.)

PMID- 20818887
TI  - Ecallantide for the treatment of acute attacks in hereditary angioedema.
AB  - BACKGROUND: Hereditary angioedema is a rare genetic disorder characterized by
      acute, intermittent, and potentially life-threatening attacks of edema of the
      skin and mucosa. We evaluated ecallantide, a newly developed recombinant plasma
      kallikrein inhibitor, for the treatment of acute attacks of angioedema. METHODS:
      In this double-blind, placebo-controlled trial, patients with hereditary
      angioedema presenting with an acute attack were randomly assigned, in a 1:1
      ratio, to receive subcutaneous ecallantide, at a dose of 30 mg, or placebo. Two
      measures of patient-reported outcomes were used to assess the response: treatment
      outcome scores, which range from +100 (designated in the protocol as significant
      improvement in symptoms) to -100 (significant worsening of symptoms), and the
      change from baseline in the mean symptom complex severity score, which range from
      +2 (representing a change from mild symptoms at baseline to severe symptoms
      after) to -3 (representing a change from severe symptoms at baseline to no
      symptoms after). The primary end point was the treatment outcome score 4 hours
      after study-drug administration. Secondary end points included the change from
      baseline in the mean symptom complex severity score at 4 hours and the time to
      significant improvement. RESULTS: A total of 71 of the 72 patients completed the
      trial. The median treatment outcome score at 4 hours was 50.0 in the ecallantide
      group and 0.0 in the placebo group (interquartile range [IQR], 0.0 to 100.0 in
      both groups; P=0.004). The median change in the mean symptom complex severity
      score at 4 hours was -1.00 (IQR, -1.50 to 0.00) with ecallantide, versus -0.50
      (IQR, -1.00 to 0.00) with placebo (P=0.01). The estimated time to significant
      improvement was 165 minutes with ecallantide versus more than 240 minutes with
      placebo (P=0.14). There were no deaths, treatment-related serious adverse events,
      or withdrawals owing to adverse events. CONCLUSIONS: Four hours after
      administration of ecallantide or placebo for acute attacks of angioedema in
      patients with hereditary angioedema, patient-reported treatment outcome scores
      and mean symptom complex severity scores were significantly better with
      ecallantide than with placebo. (Funded by Dyax; ClinicalTrials.gov number,
      NCT00262080.)

PMID- 20818888
TI  - Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema.
AB  - BACKGROUND: Hereditary angioedema is characterized by recurrent attacks of
      angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key
      mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist.
      METHODS: In two double-blind, randomized, multicenter trials, we evaluated the
      effect of icatibant in patients with hereditary angioedema presenting with
      cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment
      (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2,
      patients received either icatibant or oral tranexamic acid, at a dose of 3 g
      daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg.
      The primary end point was the median time to clinically significant relief of
      symptoms. RESULTS: A total of 56 and 74 patients underwent randomization in the
      FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5
      hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14)
      and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the
      FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13
      recipients of placebo needed treatment with rescue medication. The median time to
      first improvement of symptoms, as assessed by patients and by investigators, was
      significantly shorter with icatibant in both trials. No icatibant-related serious
      adverse events were reported. CONCLUSIONS: In patients with hereditary angioedema
      having acute attacks, we found a significant benefit of icatibant as compared
      with tranexamic acid in one trial and a nonsignificant benefit of icatibant as
      compared with placebo in the other trial with regard to the primary end point.
      The early use of rescue medication may have obscured the benefit of icatibant in
      the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and
      NCT00500656.)

PMID- 20818889
TI  - Suicide-related events in patients treated with antiepileptic drugs.
AB  - BACKGROUND: A previous meta-analysis of data from clinical trials showed an
      association between antiepileptic drugs and suicidality (suicidal ideation,
      behavior, or both). We used observational data to examine the association between
      the use or nonuse of antiepileptic drugs and suicide-related events (attempted
      suicides and completed suicides) in patients with epilepsy, depression, or
      bipolar disorder. METHODS: We used data collected as part of the clinical care of
      patients who were representative of the general population in the United Kingdom
      to identify patients with epilepsy, depression, or bipolar disorder and to
      determine whether they received antiepileptic drugs. We estimated the incidence
      rate of suicide-related events and used logistic regression to compute odds
      ratios, controlling for confounding factors. RESULTS: In a cohort of 5,130,795
      patients, the incidence of suicide-related events per 100,000 person-years was
      15.0 (95% confidence interval [CI], 14.6 to 15.5) among patients without
      epilepsy, depression, bipolar disorder, or antiepileptic-drug treatment, 38.2
      (95% CI, 26.3 to 53.7) among patients with epilepsy who did not receive
      antiepileptic drugs, and 48.2 (95% CI, 39.4 to 58.5) among patients with epilepsy
      who received antiepileptic drugs. In adjusted analyses, the use of antiepileptic
      drugs was not associated with an increased risk of suicide-related events among
      patients with epilepsy (odds ratio, 0.59; 95% CI, 0.35 to 0.98) or bipolar
      disorder (1.13; 95% CI, 0.35 to 3.61) but was significantly associated with an
      increased risk among patients with depression (1.65; 95% CI, 1.24 to 2.19) and
      those who did not have epilepsy, depression, or bipolar disorder (2.57; 95% CI,
      1.78 to 3.71). CONCLUSIONS: The current use of antiepileptic drugs was not
      associated with an increased risk of suicide-related events among patients with
      epilepsy, but it was associated with an increased risk of such events among
      patients with depression and among those who did not have epilepsy, depression,
      or bipolar disorder.

PMID- 20818891
TI  - Clinical practice. Transverse myelitis.

PMID- 20818892
TI  - Images in clinical medicine. Velvet palms.

PMID- 20818890
TI  - Myocardial fibrosis as an early manifestation of hypertrophic cardiomyopathy.
AB  - BACKGROUND: Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy and
      a proposed substrate for arrhythmias and heart failure. In animal models,
      profibrotic genetic pathways are activated early, before hypertrophic remodeling.
      Data showing early profibrotic responses to sarcomere-gene mutations in patients
      with hypertrophic cardiomyopathy are lacking. METHODS: We used echocardiography,
      cardiac magnetic resonance imaging (MRI), and serum biomarkers of collagen
      metabolism, hemodynamic stress, and myocardial injury to evaluate subjects with
      hypertrophic cardiomyopathy and a confirmed genotype. RESULTS: The study involved
      38 subjects with pathogenic sarcomere mutations and overt hypertrophic
      cardiomyopathy, 39 subjects with mutations but no left ventricular hypertrophy,
      and 30 controls who did not have mutations. Levels of serum C-terminal propeptide
      of type I procollagen (PICP) were significantly higher in mutation carriers
      without left ventricular hypertrophy and in subjects with overt hypertrophic
      cardiomyopathy than in controls (31% and 69% higher, respectively; P<0.001). The
      ratio of PICP to C-terminal telopeptide of type I collagen was increased only in
      subjects with overt hypertrophic cardiomyopathy, suggesting that collagen
      synthesis exceeds degradation. Cardiac MRI studies showed late gadolinium
      enhancement, indicating myocardial fibrosis, in 71% of subjects with overt
      hypertrophic cardiomyopathy but in none of the mutation carriers without left
      ventricular hypertrophy. CONCLUSIONS: Elevated levels of serum PICP indicated
      increased myocardial collagen synthesis in sarcomere-mutation carriers without
      overt disease. This profibrotic state preceded the development of left
      ventricular hypertrophy or fibrosis visible on MRI. (Funded by the National
      Institutes of Health and others.)

PMID- 20818893
TI  - Clinical problem-solving. Thinking inside the box.

PMID- 20818894
TI  - Hereditary angioedema--therapies old and new.

PMID- 20818895
TI  - Stereotactic radiosurgery for the management of brain metastases.

PMID- 20818896
TI  - Redesign of internal-medicine teaching.

PMID- 20818897
TI  - Helicobacter pylori infection.

PMID- 20818898
TI  - Nonadherence to imatinib during an economic downturn.

PMID- 20818899
TI  - Immigrants' experience with publicly funded private health insurance.

PMID- 20818900
TI  - Indoor tanning--science, behavior, and policy.

PMID- 20818902
TI  - Intensive blood-pressure control in hypertensive chronic kidney disease.
AB  - BACKGROUND: In observational studies, the relationship between blood pressure and
      end-stage renal disease (ESRD) is direct and progressive. The burden of
      hypertension-related chronic kidney disease and ESRD is especially high among
      black patients. Yet few trials have tested whether intensive blood-pressure
      control retards the progression of chronic kidney disease among black patients.
      METHODS: We randomly assigned 1094 black patients with hypertensive chronic
      kidney disease to receive either intensive or standard blood-pressure control.
      After completing the trial phase, patients were invited to enroll in a cohort
      phase in which the blood-pressure target was less than 130/80 mm Hg. The primary
      clinical outcome in the cohort phase was the progression of chronic kidney
      disease, which was defined as a doubling of the serum creatinine level, a
      diagnosis of ESRD, or death. Follow-up ranged from 8.8 to 12.2 years. RESULTS:
      During the trial phase, the mean blood pressure was 130/78 mm Hg in the intensive
      control group and 141/86 mm Hg in the standard-control group. During the cohort
      phase, corresponding mean blood pressures were 131/78 mm Hg and 134/78 mm Hg. In
      both phases, there was no significant between-group difference in the risk of the
      primary outcome (hazard ratio in the intensive-control group, 0.91; P=0.27).
      However, the effects differed according to the baseline level of proteinuria
      (P=0.02 for interaction), with a potential benefit in patients with a protein-to
      creatinine ratio of more than 0.22 (hazard ratio, 0.73; P=0.01). CONCLUSIONS: In
      overall analyses, intensive blood-pressure control had no effect on kidney
      disease progression. However, there may be differential effects of intensive
      blood-pressure control in patients with and those without baseline proteinuria.
      (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases,
      the National Center on Minority Health and Health Disparities, and others.)

PMID- 20818901
TI  - Effect of sibutramine on cardiovascular outcomes in overweight and obese
      subjects.
AB  - BACKGROUND: The long-term effects of sibutramine treatment on the rates of
      cardiovascular events and cardiovascular death among subjects at high
      cardiovascular risk have not been established. METHODS: We enrolled in our study
      10,744 overweight or obese subjects, 55 years of age or older, with preexisting
      cardiovascular disease, type 2 diabetes mellitus, or both to assess the
      cardiovascular consequences of weight management with and without sibutramine in
      subjects at high risk for cardiovascular events. All the subjects received
      sibutramine in addition to participating in a weight-management program during a
      6-week, single-blind, lead-in period, after which 9804 subjects underwent random
      assignment in a double-blind fashion to sibutramine (4906 subjects) or placebo
      (4898 subjects). The primary end point was the time from randomization to the
      first occurrence of a primary outcome event (nonfatal myocardial infarction,
      nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death).
      RESULTS: The mean duration of treatment was 3.4 years. The mean weight loss
      during the lead-in period was 2.6 kg; after randomization, the subjects in the
      sibutramine group achieved and maintained further weight reduction (mean, 1.7
      kg). The mean blood pressure decreased in both groups, with greater reductions in
      the placebo group than in the sibutramine group (mean difference, 1.2/1.4 mm Hg).
      The risk of a primary outcome event was 11.4% in the sibutramine group as
      compared with 10.0% in the placebo group (hazard ratio, 1.16; 95% confidence
      interval [CI], 1.03 to 1.31; P=0.02). The rates of nonfatal myocardial infarction
      and nonfatal stroke were 4.1% and 2.6% in the sibutramine group and 3.2% and 1.9%
      in the placebo group, respectively (hazard ratio for nonfatal myocardial
      infarction, 1.28; 95% CI, 1.04 to 1.57; P=0.02; hazard ratio for nonfatal stroke,
      1.36; 95% CI, 1.04 to 1.77; P=0.03). The rates of cardiovascular death and death
      from any cause were not increased. CONCLUSIONS: Subjects with preexisting
      cardiovascular conditions who were receiving long-term sibutramine treatment had
      an increased risk of nonfatal myocardial infarction and nonfatal stroke but not
      of cardiovascular death or death from any cause. (Funded by Abbott;
      ClinicalTrials.gov number, NCT00234832.)

PMID- 20818906
TI  - Images in clinical medicine. Bilateral blurred vision in a "healthy" adult.

PMID- 20818904
TI  - Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer.
AB  - BACKGROUND: Primary debulking surgery before initiation of chemotherapy has been
      the standard of care for patients with advanced ovarian cancer. METHODS: We
      randomly assigned patients with stage IIIC or IV epithelial ovarian carcinoma,
      fallopian-tube carcinoma, or primary peritoneal carcinoma to primary debulking
      surgery followed by platinum-based chemotherapy or to neoadjuvant platinum-based
      chemotherapy followed by debulking surgery (so-called interval debulking
      surgery). RESULTS: Of the 670 patients randomly assigned to a study treatment,
      632 (94.3%) were eligible and started the treatment. The majority of these
      patients had extensive stage IIIC or IV disease at primary debulking surgery
      (metastatic lesions that were larger than 5 cm in diameter in 74.5% of patients
      and larger than 10 cm in 61.6%). The largest residual tumor was 1 cm or less in
      diameter in 41.6% of patients after primary debulking and in 80.6% of patients
      after interval debulking. Postoperative rates of adverse effects and mortality
      tended to be higher after primary debulking than after interval debulking. The
      hazard ratio for death (intention-to-treat analysis) in the group assigned to
      neoadjuvant chemotherapy followed by interval debulking, as compared with the
      group assigned to primary debulking surgery followed by chemotherapy, was 0.98
      (90% confidence interval [CI], 0.84 to 1.13; P=0.01 for noninferiority), and the
      hazard ratio for progressive disease was 1.01 (90% CI, 0.89 to 1.15). Complete
      resection of all macroscopic disease (at primary or interval surgery) was the
      strongest independent variable in predicting overall survival. CONCLUSIONS:
      Neoadjuvant chemotherapy followed by interval debulking surgery was not inferior
      to primary debulking surgery followed by chemotherapy as a treatment option for
      patients with bulky stage IIIC or IV ovarian carcinoma in this study. Complete
      resection of all macroscopic disease, whether performed as primary treatment or
      after neoadjuvant chemotherapy, remains the objective whenever cytoreductive
      surgery is performed. (Funded by the National Cancer Institute;
      ClinicalTrials.gov number, NCT00003636.)

PMID- 20818905
TI  - Clinical practice. Calcium kidney stones.

PMID- 20818907
TI  - Clinical problem-solving. Hard to conceive.

PMID- 20818908
TI  - Sibutramine--another flawed diet pill.

PMID- 20818909
TI  - Hypertension control in African-American patients with chronic kidney disease.

PMID- 20818910
TI  - Fine-tuning therapy for acute coronary syndromes.

PMID- 20818911
TI  - The disclosure dilemma--large-scale adverse events.

PMID- 20818912
TI  - Hemolytic anemia after eculizumab in paroxysmal nocturnal hemoglobinuria.

PMID- 20818914
TI  - Effect of cyclosporin A on proliferation and differentiation of human periodontal
      ligament cells.
AB  - OBJECTIVE: Cyclosporin A (CsA) is widely used to prevent rejection after organ
      transplantation. However, it also causes several side-effects, including gingival
      overgrowth and bone resorption. Cellular mechanisms underlying the effect of CsA
      on periodontal tissue remain unclear. In this study, we investigated the effect
      of CsA on the proliferation and expression of characteristic markers in
      periodontal ligament cells (PDLs). MATERIAL AND METHODS: The proliferation and
      viability of PDLs were measured by direct cell counting and 3,4,5-dimethylthiazol
      2-yl-2,5-diphenyl tetrazolium bromide assay, respectively. mRNA expression levels
      of the specific proteins alkaline phosphatase (ALP), osteocalcin (OC) and
      collagen type 1 (Coll-1) were quantified using real-time polymerase chain
      reaction. Finally, ALP activity of PDLs was investigated using a specific
      colorimetric assay. RESULTS: We found that proliferation of PDLs was stimulated
      by 0.01-0.1 MUg/ml CsA and unaffected by 1 MUg/ml CsA. The viability of PDLs was
      increased by 0.1 MUg/ml CsA and not affected by 0.01 MUg/ml and 1 MUg/ml CsA.
      Furthermore, the mRNA expression levels of ALP, OC and Coll-1 in PDLs were
      significantly increased upon stimulation with 0.1 MUg/ml CsA for 24 h or by
      stimulation with 0.01 MUg/ml CsA for 48 h. In contrast, significantly lower
      expression levels of all three proteins in PDLs were observed upon stimulation
      with 1 MUg/ml CsA for 48 h. The ALP activity of PDLs exhibited a similar pattern
      of changes upon CsA stimulation. CONCLUSION: Our data demonstrated that CsA may
      influence both the proliferation and differentiation of human PDLs, which may
      play an important role in the homeostasis of periodontal tissue.

PMID- 20818903
TI  - Dose comparisons of clopidogrel and aspirin in acute coronary syndromes.
AB  - BACKGROUND: Clopidogrel and aspirin are widely used for patients with acute
      coronary syndromes and those undergoing percutaneous coronary intervention (PCI).
      However, evidence-based guidelines for dosing have not been established for
      either agent. METHODS: We randomly assigned, in a 2-by-2 factorial design, 25,086
      patients with an acute coronary syndrome who were referred for an invasive
      strategy to either double-dose clopidogrel (a 600-mg loading dose on day 1,
      followed by 150 mg daily for 6 days and 75 mg daily thereafter) or standard-dose
      clopidogrel (a 300-mg loading dose and 75 mg daily thereafter) and either higher
      dose aspirin (300 to 325 mg daily) or lower-dose aspirin (75 to 100 mg daily).
      The primary outcome was cardiovascular death, myocardial infarction, or stroke at
      30 days. RESULTS: The primary outcome occurred in 4.2% of patients assigned to
      double-dose clopidogrel as compared with 4.4% assigned to standard-dose
      clopidogrel (hazard ratio, 0.94; 95% confidence interval [CI], 0.83 to 1.06;
      P=0.30). Major bleeding occurred in 2.5% of patients in the double-dose group and
      in 2.0% in the standard-dose group (hazard ratio, 1.24; 95% CI, 1.05 to 1.46;
      P=0.01). Double-dose clopidogrel was associated with a significant reduction in
      the secondary outcome of stent thrombosis among the 17,263 patients who underwent
      PCI (1.6% vs. 2.3%; hazard ratio, 0.68; 95% CI, 0.55 to 0.85; P=0.001). There was
      no significant difference between higher-dose and lower-dose aspirin with respect
      to the primary outcome (4.2% vs. 4.4%; hazard ratio, 0.97; 95% CI, 0.86 to 1.09;
      P=0.61) or major bleeding (2.3% vs. 2.3%; hazard ratio, 0.99; 95% CI, 0.84 to
      1.17; P=0.90). CONCLUSIONS: In patients with an acute coronary syndrome who were
      referred for an invasive strategy, there was no significant difference between a
      7-day, double-dose clopidogrel regimen and the standard-dose regimen, or between
      higher-dose aspirin and lower-dose aspirin, with respect to the primary outcome
      of cardiovascular death, myocardial infarction, or stroke. (Funded by Sanofi
      Aventis and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00335452.)

PMID- 20818913
TI  - Improving clinical outcomes using adoptively transferred immune cells from
      umbilical cord blood.
AB  - Because of the necessary immunodepletion prior to cord blood transplantation as
      well as the immaturity of cord blood immune cells, recipients experience a high
      incidence of viral infection in addition to complications observed after
      hematopoietic stem cell transplantation, such as relapse and graft-versus-host
      disease. We describe current immunotherapeutic approaches to treating these
      complications, including the generation of antigen-specific T cells from cord
      blood, redirecting cord blood T cells using chimeric antigen receptors, and
      generating cord blood-derived natural killer cells and regulatory T cells.

PMID- 20818915
TI  - Overall job satisfaction among dentists in Sweden and Denmark: A comparative
      study, measuring positive aspects of work.
AB  - OBJECTIVE: Human service work differs from industrial work, which should be
      considered when organizing work. Previous research has shown organizational
      differences in the perceptions of work, often with a focus on negative aspects.
      The aim of this study was to analyse the overall job satisfaction among private-
      and public-practising dentists in Sweden and Denmark. This also implied a
      description of the questionnaire Swedish and Danish Dentists' Perceptions of Good
      Work about opportunities and positive and rewarding aspects of work. MATERIAL AND
      METHODS: A questionnaire covering the multidimensional concept of good work was
      developed. A total of 1835 dentists randomly sampled from the dental associations
      were sent a questionnaire in November 2008. A special non-response study was
      performed. Principal components analysis (PCA) was used to create a measure of
      overall job satisfaction, comparing four organizational subgroups. RESULTS: The
      average net response rate was 68% (n = 1226). The special non-response study of
      the Danish private practitioners showed more males, managers and dentists with
      more working hours than the respondents. PCA of three satisfaction questions
      showed a stable one-factor solution. There were differences in job satisfaction,
      with Danish public dentists ranked highest in overall job satisfaction and
      Swedish public dentists lowest. CONCLUSIONS: There were organizational
      differences in the perception of job satisfaction. Further analysis of how the
      human service is organized in the different groups is needed.

PMID- 20818916
TI  - The effect of laser treatment on bonding between zirconia ceramic surface and
      resin cement.
AB  - OBJECTIVE: The purpose of this in-vitro study was to evaluate and compare the
      effects of different surface treatments and laser irradiation on the shear bond
      strength of resin cement to zirconia-based ceramic. MATERIAL AND METHODS: Forty
      zirconia core specimens (10-mm diameter, 2-mm thickness) were produced and
      embedded in the centers of autopolymerizing acrylic resin blocks. Subsequently,
      specimens were randomly divided into four groups, each containing 10 specimens,
      for different surface treatment methods. The details of the groups are as
      follows: Group C, no treatment applied (control); Group SB, bonding surfaces of
      ceramic disks were airborne particle-abraded with 110-MUm alumina oxide
      particles; Group HF, bonding surfaces of ceramic disks were etched with 9.6%
      hydrofluoric acid; and Group L, bonding surfaces of ceramic disks were irradiated
      by a CO2 laser. A total of 40 composite resin disks were fabricated and cemented
      with an adhesive resin cement to the specimen surfaces. A universal test machine
      was used for the shear bond strength test at a crosshead speed of 1 mm/min.
      RESULTS: The highest shear bond strength values were obtained with Group L (20.99
      +/- 3.77 MPa) and the lowest values with Group C (13.39 +/- 3.10 MPa). Although
      there was no significant difference between Groups C, HF and SB (P > 0.05), Group
      L showed a significant difference from all other groups (p < 0.05). CONCLUSION:
      All surface treatment methods improved the bond strength between resin cement and
      the zirconium oxide ceramic surface. CO2 laser etching may represent an effective
      method for conditioning zirconia surfaces, enhancing micromechanical retention
      and improving the bond strength of resin cement on zirconia ceramic.

PMID- 20818917
TI  - Combined application of oto-endoscopes and nasal endoscopes for resection of
      dermoid tumor in eustachian tube.
AB  - Dermoid tumor in the eustachian tube (DTIET) is a congenital disease. Our patient
      had the symptom of discharging pus in the left ear when he was about 1 year old.
      Due to lack of understanding of the disease at that time, he was misdiagnosed as
      having cholesteatoma, for which he underwent three surgical operations in the
      middle ear. Recently, with detailed preoperative imaging estimation and full
      consideration of surgical risks, under the guidance of TV, using oto-endoscopes
      and nasal endoscopes jointly, the DTIET was resected completely via the combined
      approach of pharyngeal and tympanic openings of the eustachian tube. This case
      indicated again that it was a space-occupying lesion in the eustachian tube. On
      the basis of the characteristic expressions of CT and MRI, the possibility of
      DTIET should be fully considered. Endoscopic technology has advantages for
      surgical operation in the eustachian tube, which might remove the mass and
      achieve the aim of minimal trauma.

PMID- 20818918
TI  - Uptake and localization mechanisms of fluorescent and colored lipid probes. 1.
      Physicochemistry of probe uptake and localization, and the use of QSAR models for
      selectivity prediction.
AB  - We outline the factors involved in precise targeting of lipids and membranes by
      probes, namely, lipid and probe chemistry, geometry/topography of probe delivery,
      and probe uptake kinetics. The special case of probe orientation within membranes
      also is considered. The varieties of commercially available fluorophores are
      described, and an overview of probe physicochemical properties (amphiphilicity,
      conjugated system size, electrical properties, head group size, lipophilicity and
      solubility) is provided together with notes on their parameterization. Probe
      lipid physicochemical interactions, and their relations to parameterization, then
      are discussed including the nature and derivation of decision-rule QSAR models,
      partitioning and insertion of probes into bulk lipids and complications of this,
      partitioning and insertion of probes into membranes, and flip-flop of probes
      across membrane leaflets. A general QSAR algorithm for understanding lipid probe
      application then is set out. Problems and limitations are outlined. Biological
      issues include varied biomembrane composition, cell line effects and toxicity of
      fluorescent probes. Methodological issues include difficulties of estimating
      certain numerical structure parameters, the impure character of many
      fluorochromes and dyes, and the perturbation of biomembrane structure by
      fluorescent probes.

PMID- 20818919
TI  - Phylogenetic analysis of Pythium insidiosum Thai strains using cytochrome oxidase
      II (COX II) DNA coding sequences and internal transcribed spacer regions (ITS).
AB  - To investigate the phylogenetic relationship among Pythium insidiosum isolates in
      Thailand, we investigated the genomic DNA of 31 P. insidiosum strains isolated
      from humans and environmental sources from Thailand, and two from North and
      Central America. We used PCR to amplify the partial COX II DNA coding sequences
      and the ITS regions of these isolates. The nucleotide sequences of both amplicons
      were analyzed by the Bioedit program. Phylogenetic analysis using genetic
      distance method with Neighbor Joining (NJ) approach was performed using the MEGA4
      software. Additional sequences of three other Pythium species, Phytophthora sojae
      and Lagenidium giganteum were employed as outgroups. The sizes of the COX II
      amplicons varied from 558-564 bp, whereas the ITS products varied from
      approximately 871-898 bp. Corrected sequence divergences with Kimura 2-parameter
      model calculated for the COX II and the ITS DNA sequences ranged between 0.0000
      0.0608 and 0.0000-0.2832, respectively. Phylogenetic analysis using both the COX
      II and the ITS DNA sequences showed similar trees, where we found three sister
      groups (A(TH), B(TH), and C(TH)) among P. insidiosum strains. All Thai isolates
      from clinical cases and environmental sources were placed in two separated sister
      groups (B(TH) and C(TH)), whereas the Americas isolates were grouped into A(TH.)
      Although the phylogenetic tree based on both regions showed similar distribution,
      the COX II phylogenetic tree showed higher resolution than the one using the ITS
      sequences. Our study indicates that COX II gene is the better of the two
      alternatives to study the phylogenetic relationships among P. insidiosum strains.

PMID- 20818921
TI  - Virulence in an insect model differs between mating types in Aspergillus
      fumigatus.
AB  - Aspergillus fumigatus is an opportunistic fungal pathogen that has recently been
      found to undergo sexual reproduction. Previous work suggested that invasiveness
      differs between mating types, and in the present study we tested whether
      virulence differs between mating types in an in vivo model, i.e., larvae of the
      wax moth Galleria mellonella. We measured virulence of 20 A. fumigatus isolates;
      three MAT1-1 isolates of environmental origin, five MAT1-1 isolates of clinical
      origin, seven MAT1-2 isolates of environmental origin and five MAT1-2 isolates of
      clinical origin. For each isolate, we measured virulence in six replicates and
      for each replicate, conidia were grown, harvested, and counted independently, and
      2,500 colony forming units were injected into each of 10 G. mellonella larvae.
      Virulence differed between mating types, with lower survival in larvae injected
      with MAT1-1 isolates. Virulence also differed between clinical and environmental
      isolates, but surprisingly larvae injected with environmental isolates had lower
      survival. Identification of the mechanisms underlying variation in virulence may
      identify novel targets for the treatment of Aspergillus infections.

PMID- 20818920
TI  - Doxorubicin induces drug efflux pumps in Candida albicans.
AB  - Candida albicans is one of the most important opportunistic fungal pathogens. It
      can cause serious fungal diseases in immunocompromised patients, including those
      with cancer. Treatment failures due to the emergence of drug-resistant C.
      albicans strains have become a serious clinical problem. Resistance incidents
      were often mediated by fungal efflux pumps which are closely related to the human
      ABC transporter P-glycoprotein (P-gp). P-gp is often overexpressed in cancer
      cells and confers resistance to many cytotoxic drugs. We examined whether
      cytotoxic drugs commonly used for cancer treatment (doxorubicin and
      cyclophosphamide) could alter the expression of genes responsible for the
      development of fluconazole resistance in Candida cells in the way they can
      influence homologous genes in cancer cell lines. ABC transporters (CDR1 and CDR2)
      and other resistance genes (MDR1 and ERG11) were tested by real-time PCR for
      their expression in C. albicans cells at the mRNA level after induction by
      antineoplastic drugs. The results were confirmed by a lacZ gene reporter system
      and verified at the protein level using GFP and immunoblotting. We showed that
      doxorubicin is a potent inducer of CDR1/CDR2 expression in C. albicans at both
      the mRNA and protein level and thus causes an increase in fluconazole MIC values.
      However, cyclophosphamide, which is not a substrate of human P-gp, did not induce
      ABC transporter expression in C. albicans. Neither doxorubicin nor
      cyclophosphamide could influence the expression of the other resistance genes
      (MDR1 and ERG11). The induction of CDR1/CDR2 by doxorubicin in C. albicans and
      the resulting alteration of antifungal susceptibility might be of clinical
      relevance for the antifungal treatment of Candida infections occurring after
      anticancer chemotherapy with doxorubicin.

PMID- 20818922
TI  - Early treatment of candidemia in adults: a review.
AB  - Invasive candidiasis is associated with high mortality, particularly in adults.
      Retrospective studies show that shorter times to treatment are correlated with a
      lower risk of death. A number of factors can be used to predict which patients
      would benefit from antifungal prophylaxis or early (pre-emptive or empirical)
      therapy. Detection of the fungal cell wall component (1->3)-beta-D-glucan (BDG)
      shows promise as an early biomarker of invasive fungal infection and may be
      useful in identifying patients who would benefit from early antifungal treatment.
      To date, no consistent early treatment strategy has evolved. Proof-of-concept
      studies are needed to assess the role of pre-emptive and empirical therapy in ICU
      patients and the relevance of BDG as an early marker of infection.

PMID- 20818923
TI  - The RGS protein Crg2 is required for establishment and progression of murine
      pulmonary cryptococcosis.
AB  - Cryptococcal regulators of G protein signaling (CRG) are important for growth,
      differentiation, and virulence of Cryptococcus neoformans. Disruption of CRG2
      resulted in dysregulated cAMP signaling and attenuated virulence, whereas
      disruption of CRG1 increased pheromone responses and enhanced virulence in the
      archetypal H99 strain. In tests with newly constructed near congenic mutants, a
      distinction between crg2Delta and crg1Delta gene expression was not apparent
      during macrophage interaction. Intranasal inoculation indicated that crg2Delta,
      crg1Delta, and wild-type strains reached the lungs within 0.5 hours of infection.
      However, CFUs were significantly decreased for crg2Delta at 2, 7, and 14 days
      post-infection. In contrast, crg1Delta proliferated to the same extent as the
      wild type (WT). Lung edema was not apparent in mice infected with crg2Delta 0.5
      hours post-infection, which showed little cellular infiltrate in comparison to
      WT. Alveolar septal thickening was most evident in mice infected with crg1Delta,
      while mice infected with WT exhibited decreased septal thickening at later time
      points. Consistent with these observations, crg2Delta was less efficient in the
      elicitation of Th2 immune responses in a multiplex cytokine assay. Our results
      suggest that Crg2 is critical for establishment of early pulmonary infection and
      for persistence of infection, Crg1 regulates virulence in a strain-specific
      manner, and crg2Delta, crg1Delta and WT can all be distinguished on the basis of
      host tissue responses.

PMID- 20818924
TI  - Aspergillosis: nosocomial or community-acquired?
AB  - Discrimination between nosocomial and community infections is important for
      investigation and prevention. Nosocomial and hospital-acquired infections require
      appropriate hospital control measures to avert additional cases. Nosocomial
      infections (NI) occur during hospitalization or are caused by microorganisms
      acquired during hospital stay. Such infections should not be evident when
      patients are admitted to the hospital. Furthermore, the definition of NI is based
      on epidemiological criteria, such as the time lapse between admission and onset,
      or microbiological criteria. This definition might be difficult to apply to
      invasive aspergillosis (IA) which often afflicts patients with severe
      immunosuppression or transplantation. Identification of the source may be
      difficult which could arise outside or inside the hospital. Another significant
      issue is the lack of valid and reproducible data on the incubation period. The
      incubation duration of IA is influenced by different individual or environmental
      determinants, including the severity of immunosuppression and air quality. The
      criteria of causality are also a means of discussing the contribution of hospital
      vs. community determinants of IA. The definition of nosocomial IA remains
      difficult. A better understanding of early events related to IA onset will help
      to prevent this disease for which the prognosis remains negative.

PMID- 20818925
TI  - Burden on UK secondary care of rotavirus disease and seasonal infections in
      children.
AB  - OBJECTIVE: Rotavirus is a common infection affecting children under 5 years,
      which leads to a significant disease burden. This burden is potentially
      exacerbated by the seasonality of rotavirus, particularly in the context of the
      seasonality of other common childhood infections. The primary study objective was
      to describe the pattern and burden of seasonal infections amongst children under
      5 years of age with particular attention placed on rotavirus and other
      gastrointestinal infections. METHODS: A retrospective analysis of all routine
      inpatient data relating to selected seasonal infections in the UK was conducted
      between 2001/02 and 2007/08 using data from Capse Healthcare Knowledge Systems
      (CHKS, England, Northern Ireland and Wales) and Information Services Division
      (ISD, Scotland). Admissions with selected diagnoses were extracted based on
      International Classification of Diseases (ICD)-10 coding. All episodes were
      processed using a HRG grouper and costs applied according to the NHS National
      Tariff. RESULTS: In the financial year 2007/08, the total number of admissions in
      the UK for children under 5 years for the selected seasonal infections was 64,879
      of which 32,126 admissions were associated with gastrointestinal infections
      including rotavirus gastroenteritis (RVGE). Seasonal peaks of gastrointestinal
      infections and RVGE occurred in the spring quarter and respiratory syncytial
      virus (RSV) and influenza in the winter quarter. Admissions for gastrointestinal
      infection including RVGE accounted for 35 003 bed days with 9922 due to RVGE. The
      total cost for admissions involving a diagnosis of seasonal infection was L56
      million. Of this, it was estimated that infections with an ICD-10 classification
      of rotavirus represented a cost of L8.6 million. CONCLUSION: Rotavirus
      contributes to the significant burden that seasonal infections place on inpatient
      paediatric resources during the winter and spring months. This study may be
      limited by issues of clinical coding and the infrequency of confirmatory
      microbiological testing in real-world practice. Vaccination might be considered
      as a means of reducing this clinical and economic burden particularly where long
      term effectiveness and ease of administration are proven.

PMID- 20818926
TI  - Potential of Baliospermum montanum against compound 48/80-induced systemic
      anaphylaxis.
AB  - CONTEXT: Decoctions of Baliospermum montanum Mull. Arg. (Euphorbiaceae) leaves
      are reported to be useful in the treatment of asthma and other respiratory
      complications in the Ayurvedic system. OBJECTIVE: To evaluate the mast cell
      stabilization and antihistaminic activities of the chloroform (BMLC) and ethanol
      (BMLE) extracts of the leaves of Baliospermum montanum. MATERIALS AND METHODS:
      The stabilization potential was studied on mouse peritoneal mast cells and the
      antihistaminic activity was carried out by determining the mortality rate of mice
      treated with toxicant (compound 48/80) and the effect on elevation of histamine
      release upon degranulation. RESULTS: The increased number of intact mast cells
      (43.640 +/- 1.7% and 61.57 +/- 1.79% at 200 and 400 mg/ kg, respectively)
      suggested that the BMLC stabilized the mast cell degranulation and showed
      decreased elevation of histamine. CONCLUSION: BMLC extract was found to be most
      effective against degranulation and release of histamine from mast cells.
      Identifying the lead from this plant will be a definite target for treating
      allergic diseases.

PMID- 20818927
TI  - Volatile oil profiles of the aerial parts of Jordanian garland, Chrysanthemum
      coronarium.
AB  - OBJECTIVE: The study evaluates, qualitatively and quantitatively, the volatile
      oil profiles of the aerial parts of Jordanian garland Chrysanthemum coronarium L.
      (Asteraceae) and compares the findings with literature reports of garland of
      other sources, in terms of general composition and content of potentially active
      components. MATERIALS AND METHODS: The chemical composition of the essential oils
      isolated by hydrodistillation from dried material composed of flowerheads (FH)
      and aerial parts except for flowerheads (AEF) was assessed by GC-FID and GC-MS.
      RESULTS AND DISCUSSION: More than 60 components were identified in the studied
      oils, corresponding to about 99.6 and 99.7% of total oil constituents of FH and
      AEF, respectively. The oil was characterized by substantial levels of
      monoterpenes (76.9% in FH and 61.9% in AEF) and moderate levels of sesquiterpenes
      (15.7% in FH and 27.7% in AEF). The oil from FH was characterized by high levels
      of oxygenated monoterpenes (64.3%, compared to 15.3% in AEF) and moderate levels
      of both monoterpene-hydrocarbons (12.6%, compared to 46.6% in AEF as the major
      fraction) and sesquiterpene-hydrocarbons (14.7%, compared to 23.5% in AEF), while
      very low levels of oxygenated sesquiterpenes were observed in both oils (1.0% in
      FH and 4.2% in AEF). The principal oil component was camphor (17.5%) in FH and
      myrcene (36.7%) in AEF. Other major components identified in the FH oil were
      santolina triene (4.3%), neoiso-3-thujanol (5.6%), cis-chrysanthenyl acetate
      (10.8%), perilla aldehyde (11.7%), iso-italicene (4.7%), phenylpropyl butanoate
      (4.9%), and germacrene D (4.3%), while Z-beta-ocimene (5.2%), isobornyl acetate
      (5.2%), E-beta-farnesene (12.1%), and germacrene D (4.5%) were the major
      constituents of AEF oil.

PMID- 20818928
TI  - Anti-inflammatory study on crude methanol extract and different fractions of
      Eremostachys laciniata.
AB  - CONTEXT: Eremostachys laciniata (L.) Bunge (Lamiaceae), which has been reported
      as a rich source of flavonoids, is one of the rarely explored species of the
      genus Eremostachys. OBJECTIVE: In this study, the crude methanol extract and
      different fractions of E. laciniata were investigated for in vivo anti
      inflammatory properties. MATERIAL AND METHODS: Shade-dried leaves of E. laciniata
      were exhaustively extracted by percolation with methanol (80%) to obtain 250 g of
      crude methanol extract (El), followed by fractionation with different organic
      solvents to get the n-hexane (Elh), chloroform (Elc), ethyl acetate (Ele),
      butanol (Elb), and water (Elw) fractions. An in vivo anti-inflammatory study of
      the crude extract and sub-crude fractions was carried out in rats using the
      carrageenan model. RESULTS: The Ele fraction was found to be the most potent
      inhibitor of edema formation by inducing a maximum inhibitory effect of 74.2% at
      the 300 mg/kg dose, during 3 h post carrageenan injection. The El extract and Elc
      fraction also showed good anti-inflammatory properties at the same dose.
      DISCUSSION: The demonstration of excellent anti-inflammatory activity by the
      plant chiefly concentrating in the Ele fraction and the appearance of peak
      activity in the latter phase of the experiment suggested the presence of
      relatively low-polar substances with arachidonic acid metabolite inhibition
      property. CONCLUSION: The plant may be an excellent source in the future for
      activity-guided isolation of important anti-inflammatory substances.

PMID- 20818929
TI  - The beta-blocker atenolol lowers the longevity-related degree of fatty acid
      unsaturation, decreases protein oxidative damage, and increases extracellular
      signal-regulated kinase signaling in the heart of C57BL/6 mice.
AB  - The interruption of the beta-adrenergic receptor signaling at the level of
      adenylyl cyclase (AC) by specifically knocking out (KO) the AC5 gene activates
      the RAF/MEK/ extracellular signal-regulated kinase (ERK) signaling pathway,
      delays bone and heart aging, and increases mean and maximum longevity in mice.
      However, the mechanisms involved in life extension in this animal model with
      increased longevity have not been clarified, although a decrease in oxidative
      stress has been proposed as mediator. Two traits link longevity and oxidative
      stress. Long-lived mammals and birds have a low rate of mitochondrial reactive
      oxygen species (mitROS) generation and a low degree of membrane fatty acid
      unsaturation, but these key factors have not been studied in AC5 KO mice. In the
      present investigation, male C57BL/6 mice were treated with the beta-blocker
      atenolol in drinking water, and oxidative stress-related parameters were measured
      in the heart. Atenolol treatment did not change the rate of mitROS production and
      oxidative damage to mitDNA (8-oxo-7,8-dihydro-2'-deoxyguanosine [8-oxodG]), but
      strongly decreased the degree of fatty acid unsaturation and the peroxidizability
      index, mainly due to decreases in 22:6n-3 and 20:4n-6 and to increases in 18:1n
      9, 16:1n-7 and 16:0 in the atenolol group. Protein oxidation and lipoxidation
      were lower in the atenolol group than in the controls. The mitochondrial complex
      I and IV content and the amount of p-ERK1/2 signaling proteins were significantly
      higher in the atenolol-treated than in the control animals. These results support
      the idea that the increased longevity of the AC5 KO mice can be due in part to an
      ERK signaling-mediated stress-resistance due to a decrease in fatty acid
      unsaturation, leading to lower lipid peroxidation and decreased lipoxidation
      derived damage to cellular proteins.

PMID- 20818930
TI  - Prospective comparison of six co-morbidity indices as predictors of 5 years post
      hospital discharge survival in the elderly.
AB  - Older patients often suffer from multiple co-morbid conditions. Few co-morbidity
      indices are valid and reliable in elderly patients and comparison between them is
      rare. Our objective was to compare the performance, relevance, and abilities of
      six widely used and validated co-morbidity indices--the Charlson Cumulative
      Illness Rating Scale-Geriatrics (CIRS), Index of Co-Existent Disease, Kaplan
      Scale, Geriatrics Index of Co-morbidity (GIC), and Chronic Disease Score--to
      predict 5 years of survival after hospital discharge. Data came from a
      prospective study with yearly follow up, conducted 2004-2009 in 444 patients
      (mean age 85 years; 74% female) discharged from the acute geriatric hospital of
      the Geneva University Hospitals. In univariate analysis, mortality was
      significantly associated with age; each supplementary year added 7% of additional
      risk; and with sex, being male increased the risk by 1.5-fold. The best
      prognostic predictor was the GIC class 4 followed by the CIRS quartile 4
      multiplying the risk of death by 4 and 3, respectively. After 1 year of
      discharge, for both scores approximately 50% of the high-score patients were
      already deceased and 80% were deceased after 5 years, compared with <5% in the
      lowest scores after 1 year and <40% after 5 years. When we entered all of the
      significant independent variables in a stepwise backward analysis, the best
      multiple regression model retained the CIRS quartile 4 as the strongest risk
      predictor followed by the GIC class 4. We conclude that the CIRS and the GIC may
      improve hospital discharge planning as being useful for clinical decision-making
      purposes and for clinical research in older patients.

PMID- 20818931
TI  - Polymorphisms in glutathione S-transferase omega-1 gene and increased risk of
      sporadic Alzheimer disease.
AB  - Previous studies examining the association between the glutathione S-transferase
      omega-1 (GSTO1) single-nucleotide polymorphisms (SNPs) and Alzheimer disease (AD)
      have yielded conflicting results. Furthermore, an effect of GSTO1 rs4925 on the
      age-at-onset (AAO) of AD was found in different studies on sporadic and familial
      AD cases, but with contrasting findings. A total sample of 103 AD patients, and
      157 age- and sex-matched unrelated caregivers from Apulia, southern Italy, were
      genotyped for the apolipoprotein E (APOE) polymorphism and the GSTO1 rs4925 and
      rs1804834 SNPs. Furthermore, we performed a haplotype analysis on these two SNPs
      on the GSTO1 locus and evaluated the possibility of interaction with APOE.
      Significant differences were observed in rs4925 genotype distribution between AD
      patients and age- and sex-matched healthy controls. Both the C/A (odds ratio [OR]
      = 3.116; 95% confidence interval [CI], 1.749-5.550) and the A/A (OR = 10.802; 95%
      CI, 3.605-32.128) genotypes resulted in an association with AD. A higher
      frequency of the allele A was observed in AD patients than in age- and sex
      matched controls (OR = 3.789; 95% CI, 2.442-5.878). No significant differences
      were observed in the rs1804834 genotype or allele frequencies between AD patients
      and controls. No significant influence of the GSTO1 genotypes on the AAO was
      observed. No significant interaction was found among the GSTO1 SNPs and APOE. In
      both AD and controls, no important linkage disequilibrium (LD) was observed among
      the markers investigated. Whereas the C-A haplotype appeared to be protective
      against AD (OR = 0.303; 95% CI, 0.204-0.451), the A-A haplotype appeared to be at
      increased risk for AD (OR = 4.014,; 95% CI, 2.528-6.382). Our findings supported
      a role of the GSTO1 rs4925 SNP in the risk of sporadic AD in southern Italy,
      suggesting that this and other variants of the GSTO1 gene could be implicated in
      AD pathogenesis.

PMID- 20818932
TI  - Prevention of liver fibrosis by triple helix-forming oligodeoxyribonucleotides
      targeted to the promoter region of type I collagen gene.
AB  - Hepatic fibrosis leading to cirrhosis remains a global health problem. The most
      common etiologies are alcoholism and viral infections. Liver fibrosis is
      associated with major changes in both quantity and composition of extracellular
      matix and leads to disorganization of the liver architecture and irreversible
      damage to the liver function. As of now there is no effective therapy to control
      fibrosis. The end product of fibrosis is abnormal synthesis and accumulation of
      type I collagen in the extracellular matrix, which is produced by activated
      stellate or Ito cells in the damaged liver. Therefore, inhibition of
      transcription of type I collagen should in principle inhibit its production and
      accumulation in liver. Normally, DNA exists in a duplex form. However, under some
      circumstances, DNA can assume triple helical (triplex) structures. Intermolecular
      triplexes, formed by the addition of a sequence-specific third strand to the
      major groove of the duplex DNA, have the potential to serve as selective gene
      regulators. Earlier, we demonstrated efficient triplex formation between the
      exogenously added triplex-forming oligodeoxyribonucleotides (TFOs) and a specific
      sequence in the promoter region of the COL1A1 gene. In this study we used a rat
      model of liver fibrosis, induced by dimethylnitrosamine, to test whether these
      TFOs prevent liver fibrosis. Our results indicate that both the 25-mer and 18-mer
      TFOs, specific for the upstream nucleotide sequence from -141 to -165 (relative
      to the transcription start site) in the 5' end of collagen gene promoter,
      effectively prevented accumulation of liver collagen and fibrosis. We also
      observed improvement in liver function tests. However, mutations in the TFO that
      eliminated formation of triplexes are ineffective in preventing fibrosis. We
      believe that these TFOs can be used as potential antifibrotic therapeutic
      molecules.

PMID- 20818933
TI  - Metabolic syndrome and short-term and long-term heart rate variability in elderly
      free of clinical cardiovascular disease: the PROOF study.
AB  - OBJECTIVE: Autonomic nervous system (ANS) activity decrease has been associated
      with a higher risk of sudden cardiovascular and cerebrovascular disease. Thus, we
      explored the relationship between ANS control of the cardiovascular system and
      metabolic syndrome. METHODS: We analyzed the relationship with both short-term
      and long-term heart rate variability (HRV) and metabolic syndrome in the cross
      sectional PROgnostic indicator OF cardiovascular and cerebrovascular events
      (PROOF) cohort study of 1,011 elderly subjects recruited amongst the inhabitants
      of the city of Saint Etienne, France, aged 65.6 +/- 0.8 years at the inclusion
      date. Physical examination included measurements of height, weight, systolic and
      diastolic blood pressure, waist circumference, and biological parameters. HRV
      variables were measured over 5-min, nighttime, and 24-h periods using Holter
      monitoring. RESULTS: After adjustment for current type 2 diabetes, depression,
      and smoking, we found that metabolic syndrome status, high-density lipoprotein
      cholesterol (HDL-C), and waist circumference were significantly (p < 0.05)
      associated with total power, very-low frequency, low-frequency/high-frequency
      (LF/HF) ratio, and normalized LF. HDL-C and metabolic syndrome status were
      significantly associated with decreased long-term HRV variables. Both nighttime
      and 24-h HRV showed closer associations with metabolic syndrome than did short
      term HRV (5-min). Metabolic syndrome severity was associated with a decrease in
      both the long-term and short-term HRV variables. CONCLUSIONS: ANS control
      alteration of the cardiovascular system was more pronounced when evaluated by
      long-term than short-term HRV recordings, particularly in women.

PMID- 20818934
TI  - Acetaminophen improves protein translational signaling in aged skeletal muscle.
AB  - BACKGROUND: Age-related muscle atrophy is characterized by increased oxidative
      stress, diminished Akt enzymatic function, and reduced phosphorylation of the
      mammalian target of rapamycin (mTOR), which can be attenuated by chronic
      acetaminophen ingestion. Here we hypothesize that age-related impairments in
      Akt/mTOR function are associated with reduced protein translational signaling,
      and that these changes, if present, can be attenuated by acetaminophen treatment.
      RESULTS: Compared to 6- and 27-month old animals, the expression of the mTOR
      complex proteins raptor and GbetaL and the phosphorylation of tuberin/TSC2
      (Thr1462) were reduced in the soleus muscles of very aged rats (33 months old).
      These changes in Akt/mTOR pathway signaling proteins were in turn associated with
      decreased phosphorylation of S6 kinase p85S6K (Thr412) and eukaryotic translation
      initiation factor-4E (eIF4E) binding protein-1 (4EBP1, Thr37/46), reduced
      phosphorylation of S6 ribosomal protein (Ser235/236), and increased inhibition of
      eIF4E by binding to 4EBP1. Age-associated alterations in the Akt/mTOR pathway
      signaling and in the phosphorylation of the stress-responsive eIF2alpha protein
      were attenuated by chronic acetaminophen treatment (30 mg/kg body weight per
      day). Ex vivo incubation of adult muscles with hydrogen peroxide mimicked the age
      related decreases seen in eIF4E and 4EBP1 phosphorylation, whereas the inclusion
      of acetaminophen in the muscle bath attenuated this effect. CONCLUSION: Aging is
      associated with impairments in the regulation of proteins thought to be important
      in controlling mRNA translation, and acetaminophen may be useful for the
      treatment of age-related muscle atrophy by reducing oxidative stress.

PMID- 20818935
TI  - Soybean and green tea polyphenols improve immune function and redox status in
      very old ovariectomized mice.
AB  - In previous work we have observed that ovariectomy in rodents, a good model of
      mimicking human ovarian hormone loss, causes premature aging of the immune
      system. The prooxidative and inflammatory state that underlies the aging process
      is the base of that premature immunosenescence. It has been found that
      nutritional interventions with polyphenolic antioxidants constitute a good
      alternative to rejuvenate age-affected immune functions. In this study, we
      administered a diet supplemented with polyphenols (coming from soybean
      isoflavones and green tea) to sham-operated and ovariectomized mature mice for 15
      weeks, until they reached a very old age. We have studied the effect of this
      supplementation on a broad range of parameters of immune function (in macrophages
      and lymphocytes) and oxidative stress (enzymatic and nonenzymatic antioxidant
      defences, oxidant compounds, and lipid peroxidation damage) in peritoneal
      leukocytes. The results showed that ovariectomy accelerates the age-related
      impairment of immune functions in very old mice as well as the oxidative and
      proinflammatory imbalance, and that the administration of soybean isoflavones and
      green tea improve the immune and redox state in these animals. Because the immune
      system is a good marker of health and a predictor of longevity, we suggest that
      an adequate nutritional treatment with polyphenols could be a highly recommended
      tool to fight against the detrimental effects of the lack of female sex hormones,
      through an improvement of the immune cell functions and redox state.

PMID- 20818936
TI  - In vitro antiplasmodial and antimicrobial potential of Tagetes erecta roots.
AB  - CONTEXT: Among strategies to combat malaria, the search for newer antimalarial
      compounds is a priority. Traditionally, Tagetes erecta Linn. (Compositae) has
      been used for the treatment of various diseases and ailments including malaria.
      OBJECTIVE: Five successive extracts (petroleum ether, chloroform, ethyl acetate,
      methanol and aqueous) of the roots of T. erecta and a new bithienyl compound, 2
      hydroxymethyl-non-3-ynoic acid 2-[2,2']-bithiophenyl-5-ethyl ester from the roots
      of the plant, were evaluated for in vitro antiplasmodial activity against
      chloroquine sensitive and resistant strains of Plasmodium falciparum. The
      extracts were also tested for in vitro antimicrobial activity against seven
      microbial strains. MATERIALS AND METHODS: The antiplasmodial screening was
      carried out using the schizont maturation inhibition assay. Preliminary
      antimicrobial screening was carried out using the agar well assay followed by
      determination of minimum inhibitory concentration (MIC) using two-fold serial
      dilutions. RESULTS: Among all the extracts tested, the ethyl acetate fraction
      exhibited significant antiplasmodial efficacy with the 50% inhibitory
      concentrations (IC(50)) of 0.02 and 0.07 mg/mL against the chloroquine sensitive
      and resistant strains of Plasmodium falciparum respectively. The new bithienyl
      compound also showed significant schizonticidal activity against both chloroquine
      sensitive and resistant strains of Plasmodium falciparum with the IC(50) values
      of 0.01 and 0.02 mg/mL. Additionally, all extracts exhibited significant
      antimicrobial activity against three Gram-positive and two Gram-negative
      bacterial and two fungal strains with MIC values ranging between 12.5-100 ug/mL.
      DISCUSSION: The new bithienyl compound was profoundly able to arrest the ring
      stages of the malarial parasites thereby exerting its antiplasmodial effect.
      CONCLUSION: The observations provide support for the ethnobotanical use of the
      plant.

PMID- 20818937
TI  - Neuropharmacological activity of hydroalcoholic extract of leaves of Colocasia
      esculenta.
AB  - CONTEXT: Although Colocasia esculenta Linn. (Araceae), commonly known as elephant
      ear (English), possesses diverse pharmacological activities in animals, little is
      known about its neuropharmacological activity. OBJECTIVE: The present study
      evaluated the neuropharmacological activities of hydroalcoholic extract of leaves
      of Colocasia esculenta (HECE) using several experimental models. MATERIALS AND
      METHODS: Adult Wistar albino rats were subjected to behavior despair and elevated
      plus maze (EPM) tests. Thiopental-induced sedation and rotarod tests were
      conducted on Swiss albino mice. RESULTS AND DISCUSSION: The effects of HECE on
      anxiety, depression, thiopental-induced sleeping time, and rotarod performance
      were evaluated. The anxiolytic activity of HECE (100, 200, and 400 mg/kg) per os
      (p.o.) was characterized by increased time spent and number of entries in open
      arms in the EPM paradigm as compared to control group (p < 0.001). The HECE (100,
      200, and 400 mg/kg, p.o.) showed dose-dependent significant reduction in duration
      of immobility (p < 0.01) in the behavior despair test. The HECE at the doses 50
      and 100 mg/kg, i.p. was found to produce a significant reduction in motor
      coordination (p < 0.001) and prolongation of thiopental-induced sleeping time (p
      < 0.001). The phytochemical screening revealed the presence of flavonoids, beta
      sitosterol, and steroids. CONCLUSIONS: The results of the study for the first
      time show that the plant possesses neuropharmacological activity, confirming the
      traditional claims. Future research should focus on the identification and the
      neurobehavioral activity of the constituents from this plant.

PMID- 20818938
TI  - Can your genes make you more prone to pneumococcal disease?

PMID- 20818940
TI  - Hepatitis C infection of B lymphocytes: more tools to address pending questions.
AB  - Hepatitis C virus (HCV) infection spreads primarily via contact with infected
      blood and can establish a persistent infection in 80% of infected individuals,
      progressively causing chronic liver disease that can lead to hepatocellular
      carcinoma or end-stage liver disease requiring a transplant. There is no vaccine,
      and current treatment with interferon and ribavirin is costly, poorly tolerated
      and ineffective for a large proportion of patients. Technical limitations have
      stifled the study of HCV immunology, and hence the correlates of resolution
      remain elusive. HCV robustly infects hepatocytes in the liver, yet HCV RNA is
      often found to be associated with peripheral blood lymphocytes and extrahepatic
      manifestations of the disease include B-cell abnormalities. The few existing
      characterized viral clones that can replicate in vitro have consistently failed
      to infect immune cells; however, some groups have detected low levels of
      replication in peripheral blood cells, hinting that occult forms of infection may
      be possible. HCV lymphotropism remains a controversial subject that needs to be
      elucidated in order to identify viral reservoirs that may provide targets for
      therapeutic intervention. The precise interactions between HCV and immune cells
      need to be determined to establish if the virus has developed mechanisms to
      modulate immune responses. In the study by Durand et al., correlations were
      sought between cell tropism and mutations in the 5 noncoding region of the HCV
      genome, known as the internal ribosome entry site. Key findings are discussed
      here, highlighting current experimental challenges that surround the topic of HCV
      lymphotropism.

PMID- 20818941
TI  - Pandemic influenza A (H1N1) in pregnant women: impact of early diagnosis and
      antiviral treatment.
AB  - Pregnant women are at increased risk for severe illness from influenza infection,
      particularly pandemics, including the current flu pandemic. Early antiviral
      therapy using oseltamivir or zanamivir may be beneficial, but limited information
      is available regarding their safety and effectiveness during pregnancy. The
      article by Siston et al. assessed the findings of a recently published paper
      describing the severity of illness due to 2009 influenza A (H1N1) infection among
      788 pregnant women reported to the CDC, stratified by timing of antiviral therapy
      and pregnancy trimester at symptom onset. The authors' findings highlight the
      potential for severe illness and high risk of mortality due to influenza A (H1N1)
      infection among pregnant women and suggest the benefit of early antiviral
      treatment in reducing intensive care unit admissions and mortality rate. The WHO
      and CDC recommendations including 2009 influenza A (H1N1) vaccination and early
      antiviral therapy in case of influenza-like illness for all pregnant women are
      discussed regarding the key findings of this paper and other published data on
      influenza A (H1N1) infection in pregnant women.

PMID- 20818943
TI  - Emergence and clinical insights into the pathology of Chikungunya virus
      infection.
AB  - Major epidemics of Chikungunya have re-emerged with millions of cases worldwide.
      What was once largely a tropical disease in poorer countries is now recognized as
      a major global health issue. The disease is perpetuated by the alphavirus
      Chikungunya, and is transmitted by Aedes mosquitoes. The infection is highly
      symptomatic, with fever, skin rash and incapacitating arthralgia, which can
      evolve to chronic arthritis and rheumatism in elderly patients. Mother-to-child
      transmission, encephalitis, Guillain-Barre syndrome and deaths have been noted.
      In this article, we will highlight the epidemiological, clinical, virological and
      immunological aspects of the disease and mention the therapies that have been
      used during recent epidemics. Novel prevention measures to control the mosquito
      and a new vaccine are highly warranted.

PMID- 20818945
TI  - Multidrug-resistant Gram-negative infections: the use of colistin.
AB  - The emergence of nosocomial infections due to multidrug-resistant Gram-negative
      bacteria led to the revival of 'forgotten' antibiotics, such as polymyxins.
      Colistin, mainly colistimethate sodium (polymyxin E), has been predominantly
      used. Recent studies suggest that colistin administered as monotherapy or
      combination therapy is an effective and safe antimicrobial agent for multidrug
      resistant Gram-negative bacteria infections. The reported colistin nephrotoxicity
      is 20% or lower. Although colistin is commonly administered intravenously, it can
      also be administered via inhalation for pneumonia/ventilator-associated pneumonia
      treatment or by the intraventricular/intrathecal route for
      meningitis/ventriculitis treatment. Randomized controlled trials are needed to
      answer clinical questions such as the appropriate colistin dose, to compare
      colistin monotherapy with combination therapy, and to determine the exact
      therapeutic role of aerosolized or intrathecal/intraventricular administration of
      colistin.

PMID- 20818946
TI  - Resistant pathogen-associated skin and skin-structure infections: antibiotic
      options.
AB  - Complicated skin and skin-structure infections (cSSSIs) are among the most common
      infections treated in the hospital setting. They are a significant clinical
      problem, partially owing to increasing resistance of infecting bacteria to
      current antibiotic therapies (nosocomial and community-acquired methicillin
      resistant Staphylococcus aureus, extended spectrum beta-lactamase-producing
      Enterobacteriaceae, and multidrug-resistant [MDR] Pseudomonas aeruginosa, among
      others). The optimal choice of antibacterial therapy among the few available
      options for infections caused by MDR pathogens is fundamental to maximize
      clinical effectiveness and minimize the likelihood of further resistance
      development. Few antimicrobial agents are currently available to treat MDR
      bacteria in cSSSIs. In this context, the use of new antibiotic agents (i.e.,
      linezolid, daptomycin and tigecycline) and the optimization of the
      pharmacodynamic targets of classic antibiotics (i.e., carbapenems) is one
      potential solution to these problems, and some of these agents are highlighted in
      this article. The purpose of this article is to provide clinicians with an
      evidence-based review of MDR pathogens causing cSSSIs, the implications of
      resistance to currently used drug therapy, and to identify new therapeutic
      options for resistant pathogens causing cSSSIs.

PMID- 20818944
TI  - Adjunctive therapy for cerebral malaria and other severe forms of Plasmodium
      falciparum malaria.
AB  - Severe malaria due to Plasmodium falciparum causes more than 800,000 deaths every
      year. Primary therapy with quinine or artesunate is generally effective in
      controlling P. falciparum parasitemia, but mortality from cerebral malaria and
      other forms of severe malaria remains unacceptably high. Long-term cognitive
      impairment is also common in children with cerebral malaria. Of the numerous
      adjunctive therapies for cerebral malaria and severe malaria studied over the
      past five decades, only one (albumin) was associated with a reduction in
      mortality. In this article, we review past and ongoing studies of adjunctive
      therapy, and examine the evidence of efficacy for newer therapies, including
      inhibitors of cytoadherence (e.g., levamisole), immune modulators (e.g.,
      rosiglitazone), agents that increase nitric oxide levels (e.g., arginine) and
      neuroprotective agents (e.g., erythropoietin).

PMID- 20818948
TI  - Updated guidelines for managing fungal diseases in hematology patients.
AB  - Many prospective open or comparative studies have been published over the last
      few years on antifungals. As invasive fungal disease remains an important cause
      of morbidity and mortality in high-risk hematology patients, the correct use of
      antifungal drugs, either as prophylaxis, empirical treatment in neutropenic
      patients or for therapy of overt disease, is of the utmost importance. Several
      international or national groups, including the Infectious Diseases Society of
      America and the European Conference on Infections in Leukaemia, have elaborated
      practice guidelines to improve the correct usage of antifungals. This article
      summarizes these guidelines, which have very similar recommendations, and
      comments on their evidence base.

PMID- 20818947
TI  - Molecular microbiological methods in the diagnosis of neonatal sepsis.
AB  - Neonatal sepsis is a major cause of neonatal mortality and morbidity. The current
      gold standard for diagnosis of sepsis, namely blood culture, suffers from low
      sensitivity and a reporting delay of approximately 48-72 h. Rapid detection of
      sepsis and institution of antimicrobial therapy may improve patient outcomes.
      Rapid and sensitive tests that can inform clinicians regarding the institution or
      optimization of antimicrobial therapy are urgently needed. The ideal diagnostic
      test should have adequate specificity and negative predictive value to reliably
      exclude sepsis and avoid unnecessary antibiotic therapy. We comprehensively
      searched for neonatal studies that evaluated molecular methods for diagnosis of
      sepsis. We identified 19 studies that were assessed with respect to assay
      methodology and diagnostic characteristics. In addition, we also reviewed newer
      molecular microbiological assays of relevance that have not been fully evaluated
      in neonates. Molecular methods offer distinct advantages over blood cultures,
      including increased sensitivity and rapid diagnosis. However, diagnostic accuracy
      and cost-effectiveness should be established before implementation in clinical
      practice.

PMID- 20818950
TI  - Immunomodulatory effect of Aegle marmelos leaf extract on freshwater fish
      Cyprinus carpio infected by bacterial pathogen Aeromonas hydrophila.
AB  - CONTEXT: Aquatic organisms (especially fish) require potent defense mechanisms to
      protect themselves against pathogen invasion and disease formation. The use of
      immunostimulants in fish culture can prevent the diseases through augmentation of
      both specific and non-specific immunity. OBJECTIVE: A study was conducted to
      investigate the efficacy of different dietary doses of Aegle marmelos (Linn.)
      Corr. Serr. (Rutaceae) leaf extract for the immune response and the disease
      resistance of the freshwater fish, Cyprinus carpio Linn. (Cyprinidae) infected by
      Aeromonas hydrophila Chester (Aeromonadaceae). MATERIALS AND METHODOLOGY:
      Hematological, specific immune response, non-specific immune response and enzyme
      assay studies were performed on fish and were scrutinized after 50 days of
      feeding trial. RESULTS: Fish were challenged with Aeromonas hydrophila at a dose
      of 1.5 * 10(4) cells/mL through intraperitoneal injection, and the hematological
      changes, the immune response, the enzyme activity and the disease resistance of
      Cyprinus carpio against the pathogen were also studied for 20 days at 5-day
      intervals. DISCUSSION: The results obtained from the study demonstrated that the
      fish fed with leaf extract of Aegle marmelos incorporated into feed significantly
      enhanced the red blood cell count, white blood cell count, hemoglobin, phagocytic
      activity, nitroblue tetrazolium chloride assay, lysozyme, pathogen clearance and
      enzyme activity compared with the control group. The survivability was higher in
      the fish which consumed leaf extract-incorporated feed, and the fish group fed
      with 5 g diet showed highest percentage survival of the fish. CONCLUSION: These
      results indicate that Aegle marmelos stimulates the immunity and makes the
      freshwater fish Cyprinus carpio more resistant to Aeromonas hydrophila.

PMID- 20818951
TI  - Functioning and disability in ischaemic heart disease.
AB  - OBJECTIVE: To describe functioning and disability in patients with stable
      ischaemic heart disease (IHD) according to the model endorsed by the
      International Classification of Functioning Disability and Health (ICF). DESIGN:
      Adult patients with IHD undergoing rehabilitation were consecutively enrolled.
      The ICF checklist and the WHO Disability Assessment Schedule II (WHO-DAS II) were
      administered in individual sessions. Patients' clinical status was described
      following NYAH criteria (New York Heart Association). Descriptive analyses were
      performed to report on clinical variables and WHO-DAS II scores. ICF categories
      reported as a problem by more than 20% of patients were described in detail.
      RESULTS: One hundred patients (mean age 62.9; 91% males, 71% in NYHA class II)
      were enrolled. Mean WHO-DAS II score was 23.9, and the most severe limitations
      are reported in life activities, getting around and in participation to social
      situations. A total of 30 ICF categories reached the threshold of 20%, 17 Body
      Functions and Structures, 13 Activities and Participation. CONCLUSIONS: ICF
      application in patients with IHD enables to enlarge the perspective on their
      health status, and provide useful information to follow the healthcare process
      from the acute setting to the outpatient management.

PMID- 20818952
TI  - Maternal serum human placental growth hormone (hPGH) at 11 to 13 weeks of
      gestation in preeclampsia.
AB  - OBJECTIVE: Human placental growth hormone (hPGH) is produced by human placenta
      and plays a central role in the maternal metabolic adjustments to pregnancy. The
      objective of this study was to investigate the maternal serum concentration of
      hPGH at 11-13 weeks of gestation in pregnancies that subsequently developed
      preeclampsia (PE), and to examine the possible association with uterine artery
      pulsatility index (PI) and maternal serum pregnancy-associated plasma protein-A
      (PAPP-A). METHODS: The maternal serum concentration of hPGH at 11-13 weeks was
      measured in a case-control study from 60 cases that developed PE and 120
      unaffected controls. The measured hPGH concentration was converted into a
      multiple of the expected median (MoM) in unaffected pregnancies. Regression
      analysis was used to determine the significance of association between hPGH MoM
      with uterine artery PI MoM and PAPP-A MoM. RESULTS: In the pregnancies that
      subsequently developed PE the median serum hPGH concentration was not
      significantly different from that in the unaffected group (0.92 versus 1.00 MoM),
      whereas uterine artery PI was increased (1.31 versus 1.01 MoM) and serum PAPP-A
      was decreased (0.76 versus 1.01 MoM). In the group that developed PE there was no
      significant association between serum hPGH MoM and gestational age at delivery,
      uterine artery PI MoM, or serum PAPP-A MoM. CONCLUSION: The finding that in the
      PE group serum hPGH level during the first trimester is normal suggests that it
      is unlikely that this hormone plays a role in the pathogenesis of PE.

PMID- 20818953
TI  - Chlamydia pneumoniae infection in preeclampsia.
AB  - OBJECTIVE: The maternal syndrome of preeclampsia results from systemic
      endothelial activation by a number of factors that primarily derive from the
      intervillous space, so-called intervillous soup. Co-precipitants, such as innate
      immune activators, may lower the threshold to develop the maternal syndrome in
      preeclampsia. We examined whether, like atherosclerosis, preeclampsia is
      associated with infection with Chlamydia pneumoniae (C. pneumoniae). STUDY
      DESIGN: A case-control study was performed on 50 women with preeclampsia, 57
      women with normal pregnancies at term, and 25 non-pregnant controls. Anti-C.
      pneumoniae antibodies were examined by enzyme-linked immunosorbent assay and C.
      pneumoniae genomic DNA (gDNA) loads were measured by real-time PCR. We also
      performed a data synthesis of the relationship between anti-C. pneumoniae
      seroprevalence and preeclampsia risk. RESULTS: Neither the number of women with
      measurable copy numbers of C. pneumoniae gDNA, the anti-C. pneumoniae
      seroprevalence, nor antibody indices of IgG, IgM, or IgA to C. pneumonia varied
      between groups. However, when measurable, gDNA copy numbers of C. pneumoniae were
      increased in women with preeclampsia compared with the normal pregnant (p < 0.05)
      and non-pregnant controls (p < 0.05). For women with measurable C. pneumoniae
      gDNA, their copy numbers were correlated with anti-C. pneumoniae IgG
      concentrations (r2 = 0.49; p < 0.0001). Data synthesis reveals that anti-C.
      pneumoniae IgG seroprevalence is associated with preeclampsia risk. CONCLUSION:
      Our data suggest an association between C. pneumoniae infection and preeclampsia.
      While not a uniform and singular precipitant of the maternal syndrome of
      preeclampsia, C. pneumoniae infection may be a co-precipitant with other
      components of the intervillous soup. Further investigations appear warranted.

PMID- 20818954
TI  - Toll-like receptor gene polymorphisms and preeclampsia risk: a case-control study
      and data synthesis.
AB  - BACKGROUND: Preeclampsia is a syndrome of exaggerated innate inflammatory
      response. It is plausible that this innate inflammation may be mediated by Toll
      like receptors (TLRs). A portion of the familial susceptibility to the
      development of preeclampsia may be mediated by single nucleotide polymorphisms
      (SNPs) in the TLR gene sequences. Published reports vary in their finding an
      association between TLR SNPs and preeclampsia risk.  METHODS: Common SNPs of the
      TLR2 (Arg753Gln) and co-segregating TLR4 (Asp299Gly and Thr399Ile) genes were
      screened in 94 women with pre-eclampsia and 176 healthy pregnancy controls. We
      performed a data synthesis of our findings with those in published reports to
      ascertain whether or not we could explain the apparent disparity in the
      literature. RESULTS: The presence of TLR2 (RR 2.57 [95% CI 1.31, 5.05]) and TLR4
      (RR 2.06 [1.16, 3.67]) SNPs aggregated with early-onset (<34 + 0 weeks), but not
      late-onset (>or=34 + 0 weeks), preeclampsia. Through synthesis of these and the
      published data, TLR polymorphisms appear to lower thresholds for early-onset and
      severe preeclampsia, but not late-onset or mild disease. CONCLUSIONS: TLR2 and
      TLR4 SNPs appear to alter susceptibility to developing the maternal syndrome of
      preeclampsia. Data synthesis of these data and other studies strengthens the
      association for early-onset and severe disease, in particular. A definitive and
      fully powered cohort study is required.

PMID- 20818955
TI  - Increased myogenic responses of resistance-sized mesenteric arteries after
      reduced uterine perfusion pressure in pregnant rats.
AB  - OBJECTIVE: A central component of preeclampsia is a reduction in utero-placental
      perfusion. We tested the hypothesis that vascular reactivity of second - order
      mesenteric arteries would be increased in a pregnant rat with reduced uterine
      perfusion pressure (RUPP). METHODS: Pregnant 10-12 week old Sprague-Dawley rats
      underwent RUPP surgery on gestational day 14, and experiments were carried out on
      day 20. SHAM operated animals were used as controls. Resistance caliber
      mesenteric arteries (200-250 MUm) were isolated, myogenic reactivity and
      responses to vasoconstrictor and vasodilator agonists were assessed utilizing a
      pressurized arteriograph system. RESULTS: RUPP resulted in maternal hypertension
      and reductions in fetal number and weight. Resistance caliber mesenteric arteries
      (200-250 MUm) were isolated, myogenic reactivity and responses to vasoconstrictor
      and vasodilator agonists were assessed utilizing a pressurized arteriograph
      system. Myogenic reactivity responses were normalized as a percent change in
      vessel diameter from an initial diameter at 20 mmHg. The mesenteric arteries from
      RUPP animals exhibited a significant increase in myogenic reactivity compared to
      SHAM controls (p < 0.05). This increased myogenicity was reversed with
      prostaglandin inhibition, suggesting a role for a vasoconstrictor prostaglandin.
      In addition to alterations in myogenic reactivity, resistance-sized arteries from
      RUPP animals have decreased responses to nitric oxide (NO) as evidenced by
      decreases in responses to methacholine (ME; P < 0.05) and no change in myogenic
      reactivity after NO synthase blockade. CONCLUSION: RUPP alters the behavior of
      resistance caliber arteries to favor a more contractile phenotype with decreased
      in NO responses, which is similar to what is seen in preeclampsia.

PMID- 20818956
TI  - Hypertensive disorders in pregnancy: screening by systolic diastolic and mean
      arterial pressure at 11-13 weeks.
AB  - OBJECTIVES: To examine the performance of screening for hypertensive disorders in
      pregnancy and to compare systolic blood pressure (BP), diastolic BP, and mean
      arterial pressure (MAP) measured by validated automated devices in a large
      population of pregnant women at 11-13 weeks. METHODS: We recorded maternal
      variables and measured BP by automated devices in 9149 women with singleton
      pregnancies. The performance of screening for preeclampsia (PE) and gestational
      hypertension (GH) by combinations of disease-specific maternal factor-derived a
      priori risk with systolic BP, diastolic BP, and MAP was determined. RESULTS:
      There were 8061 cases that were unaffected by PE or GH, 37 that developed PE
      requiring delivery before 34 weeks (early-PE), 128 with late-PE, and 140 with GH.
      The systolic BP, diastolic BP, and MAP were significantly higher in early-PE,
      late-PE, and GH than in the controls (p < 0.0001). The systolic BP was
      significantly higher in early-PE than in late-PE (p = 0.008) and both systolic BP
      and MAP were significantly higher in early-PE than in GH (p < 0.01). The best
      performance in screening was provided by MAP. The detection rate of early-PE at a
      10% false-positive rate increased from 47% in screening by maternal factor
      derived a priori risk alone to 76% in screening by its combination with MAP. The
      respective detection rates for late-PE increased from 41 to 52% and for GH
      increased from 31 to 48%. CONCLUSION: The measurement of BP can be combined with
      the maternal factor-derived a priori risk to provide effective first-trimester
      screening for PE and GH.

PMID- 20818957
TI  - Examining the effect of maternal obesity on outcome of labor induction in
      patients with preeclampsia.
AB  - OBJECTIVE: The objective of this investigation was to evaluate the effect of
      maternal obesity, as measured by prepregnancy body mass index (BMI), on the mode
      of delivery in women undergoing indicated induction of labor for preeclampsia.
      STUDY DESIGN: Following Institutional Review Board (IRB) approval, patients with
      preeclampsia who underwent an induction of labor from 1997 to 2007 were
      identified from a perinatal information database, which included historical and
      clinical information. Data analysis included bivariable and multivariable
      analyses of predictor variables by mode of delivery. An artificial neural network
      was trained and externally validated to independently examine predictors of mode
      of delivery among women with preeclampsia. RESULTS: Six hundred and eight women
      met eligibility criteria and were included in this investigation. Based on
      multivariable logistic regression (MLR) modeling, a 5-unit increase in BMI yields
      a 16% increase in the odds of cesarean delivery. An artificial neural network
      trained and externally validated confirmed the importance of obesity in the
      prediction of mode of delivery among women undergoing labor induction for
      preeclampsia. CONCLUSION: Among patients who are affected by preeclampsia,
      obesity complicates labor induction. The risk of cesarean delivery is enhanced by
      obesity, even with small increases in BMI. Prediction of mode of delivery by an
      artificial neural network performs similar to MLR among patients undergoing labor
      induction for preeclampsia.

PMID- 20818958
TI  - The relationship between plasma level of Se and preeclampsia.
AB  - OBJECTIVE: To determine the relationship of selenium plasma level and
      preeclampsia, as an antioxidant, against reduction damage of free radicals.
      METHODS: A case control study was carried out on 40 preeclamptic, and 40 healthy
      pregnant women in 34-39(th) week of gestation who were matched on the age of
      pregnancy and mineral supplements intake, in Iran. The plasma level of selenium
      measured by atomic absorption. Data was analyzed by using the statistical tests
      (t-test, chi-square, regression), alpha = 0 .05. RESULTS: The mean plasma level
      of selenium significantly decreased in preeclamptic women compared to healthy
      pregnant women (p = 0.001). There was a relationship between plasma levels of
      selenium and preeclampsia. The odds of having preeclampsia in women who were at
      the bottom tertile of plasma selenium was 4.96-fold (OR = 4.96, CI 95%; 1.56
      15.6, P = 0.006) and in the second tertile 3.94-fold greater (OR = 3.94, CI 95%;
      1.26-12.33, P = 0.019) than third tertile of plasma selenium. Selenium plasma
      level under 60 MUg/L has a sensitivity of 87.5%, a positive predictive value of
      64.8% and Youden index was 0.4. CONCLUSION: The result of this study shows that
      the reduction of selenium plasma level in preeclamptic women in comparison with
      healthy pregnant women may demonstrate a higher demand of Se in preeclamptic
      pregnancies. Selenium plasma level <60 MUg/l might be a favorite cut-off point
      for screening of preeclampsia specially in pregnancies with low selenium plasma
      level; however, it may not be a favorite predictive.

PMID- 20818959
TI  - Pregnancy-associated parvovirus B19 infection causing postinfectious
      glomerulonephritis.
AB  - BACKGROUND: Postinfectious glomerulonephritis due to parvovirus B19 during
      pregnancy is not described in the literature. OBJECTIVE: A case and renal biopsy
      of postinfectious glomerulonephritis due to parvovirus B19 during pregnancy is
      presented. DISCUSSION AND CONCLUSIONS: The patient contracted "fifth disease,"
      parvovirus B19, in the 10th week of pregnancy, and 2 weeks later developed
      hypertension, nephrotic range proteinuria, pleural effusions, and evidence of
      pure red cell aplasia. Serum parvovirus B19 IgM was positive; a renal biopsy was
      performed, revealing diffuse proliferative glomerulonephritis with
      immunofluorescent and electron microscopic changes consistent with postinfectious
      glomerulonephritis. Renal, hemodynamical, and hematological parameters returned
      to normal by the 16th week gestation, and the pregnancy proceeded without further
      complication to the mother, with term delivery of a healthy infant.

PMID- 20818960
TI  - Subsequent pregnancy outcome after first pregnancy with normotensive early-onset
      intrauterine growth restriction at <34 weeks of gestation.
AB  - OBJECTIVE: The aim of this study was to evaluate maternal and fetal outcome of
      the subsequent pregnancy of primiparous women with a history of early-onset
      intrauterine growth restriction (IUGR), prompting delivery before 34 weeks of
      gestation, without concomitant maternal hypertensive disease. DESIGN:
      Retrospective cohort study. SETTING: Tertiary center in the Netherlands.
      POPULATION: Women with a normotensive first pregnancy complicated by early-onset
      severe IUGR, prompting delivery before 34 weeks of gestation. METHODS:
      Reproductive follow-up data were recorded for 22 women with a normotensive first
      pregnancy complicated by early-onset severe IUGR before 34 weeks, referred to the
      University Medical Centre Utrecht, the Netherlands, between 1993 and 2005. MAIN
      OUTCOME MEASURES: Main outcome measures were recurrent IUGR, perinatal mortality,
      preterm delivery, preeclampsia (PE), pregnancy-induced hypertension, and other
      major obstetric complications, for example placental abruption. RESULTS: Mean
      gestational age at delivery was 29.4 weeks for the index pregnancy compared to
      36.4 weeks for the next pregnancy. IUGR recurred in six pregnancies (27.3%). Four
      subsequent pregnancies were complicated by hypertensive disorders. Perinatal
      mortality was 72.7% in the index pregnancy, compared to 13.6% in the second
      pregnancy. Overall, 11 women (54.5%) had an uneventful pregnancy. CONCLUSION:
      Women with first pregnancy early-onset IUGR, without concomitant maternal
      hypertensive disease, frequently develop severe perinatal complications in their
      subsequent pregnancy.

PMID- 20818961
TI  - Inflammatory mediators gene polymorphisms in preeclampsia.
AB  - OBJECTIVE: To assess a possible relation between proinflammatory mediators (IL
      1R1, IL-12, IL-18, TLR-2, and TLR-4) gene polymorphisms and preeclampsia (PE).
      METHODS: Genotyping was performed on 109 preeclamptic patients and 174 healthy
      fertile women with at least two previous successful pregnancies (controls).
      chi(2) or Fisher's exact test were used to compare genotype frequencies. The
      control group included 174 pregnant women matched by race to the study group.
      RESULTS: Genotypic and allelic distributions for all six polymorphisms were
      similar between the study and control groups. IL-1R1 (PstI, rs2234650): p = 0.82
      ; IL-12 (+1188, rs3212227): p = 0.93; IL-18 (-137, rs187238): p = 0.74 ; IL-18 (
      607, rs1946519): p = 0.22; TLR-2 (+2258, rs5743708): p = 0.97; and TLR-4 (+896,
      rs4986790): p = 0.23. CONCLUSION: The analyzed gene polymorphisms are not
      associated with PE.

PMID- 20818962
TI  - Synthesis, self-assembly, and characterization of PEG-coated iron oxide
      nanoparticles as potential MRI contrast agent.
AB  - AIM: Investigated the self-assembly and characterization of novel antifouling
      polyethylene glycol (PEG)-coated iron oxide nanoparticles as nanoprobes for
      magnetic resonance imaging (MRI) contrast agent. METHOD: Monodisperse oleic acid
      coated superparamagnetic iron oxide cores are synthesized by thermal
      decomposition of iron oleate. The self-assembly behavior between iron oxide cores
      and PEG-lipid conjugates in water and their characteristics are confirmed by
      transmission electron microscope, X-ray diffraction, thermogravimetric analysis,
      Fourier transform infrared spectroscopy, and vibrating sample magnetometer.
      RESULT: Dynamic light scattering shows superparamagnetic iron oxide nanoparticles
      coated with PEG are stable in water for pH of 3-10 and ionic strengths up to 0.3
      M NaCl, and are protein resistant in physiological conditions. Additionally, in
      vitro MRI study demonstrates the efficient magnetic resonance imaging contrast
      characteristics of the iron oxide nanoparticles. CONCLUSION: The result indicates
      that the novel antifouling PEG-coated superparamagnetic iron oxide nanoparticles
      could potentially be used in a wide range of applications such as biotechnology,
      MRI, and magnetic fluid hyperthermia.

PMID- 20818963
TI  - Comparison in purity and antitumor effect of brand and generic paclitaxel against
      human ovarian cancer cells by an in vitro experimental model.
AB  - CONTEXT: The purity and the therapeutic effectiveness of the generic paclitaxel
      have not yet been examined and compared to the original brand form. OBJECTIVE:
      This study aimed to compare the in vitro purity and biological effects of
      original brand form (Taxol) and a generic drug of paclitaxel. MATERIALS AND
      METHODS: Purity was determined by high-performance liquid chromatography
      analysis, cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium
      bromide assay, cell proliferation by clonogenic assay, morphology by Liu's
      staining, and cell cycle distribution by DNA histogram. RESULTS: Taxol and
      generic paclitaxel shared similar high-performance liquid chromatography profiles
      with a major peak at the same retention time and ultraviolet spectrum. Generic
      paclitaxel inhibited the cell viability to an extent greater than Taxol. By
      assessing the IC(50), generic paclitaxel also exhibited a greater inhibitory
      activity on clonogenicity of human ovarian adenocarcinoma SKOV-3 cells. Although
      both generic paclitaxel and Taxol arrested SKOV-3 and ES-2 cells at G2/M phase
      with concurrent development of hypoploid and polyploid cells, Taxol treatment
      exhibited markedly less extent of these changes. Observation of cellular
      morphology revealed a greater amount of mitotic catastrophe-like and apoptotic
      cells in generic paclitaxel-treated cells than Taxol-treated cells. DISCUSSION
      AND CONCLUSION: The results suggest that generic paclitaxel may possess a greater
      cell death inducing capacity and clonogenicity inhibitory activity against
      ovarian cancer cells than the original brand Taxol of the same purity. We
      conclude that this experimental model for assessing the difference between
      generic and brand name drugs might be considered as a reference while determining
      their interchangeability and could be easily established in a hospital-based
      laboratory.

PMID- 20818964
TI  - Surface responses and desirability functions to determine optimal granulation
      domains.
AB  - BACKGROUND: Single pot mixer-granulator-dryer (high-shear granulator with in situ
      double jacket vacuum drying) and multiphase equipment (high-shear granulator
      associated with fluid bed dryer) are classically used for wet granulation. At
      present time, industrial production imperatives may require to switch one
      formulation from one equipment to another. METHOD: To compare the two processes
      and to define, for each of them, the optimal formulation domain, experiments were
      organized according to Doehlert experimental designs. Response surfaces were used
      to identify the levels of each factor (binder and filler ratios) inducing the
      more satisfying responses. The contribution of binder and filler ratios to
      granule properties was highlighted according to the process. Then the
      desirability function was used to determine and compare the optimal formulation
      domain for each process. RESULTS AND CONCLUSION: In the studied formulation
      domain and for the considered equipment, the transposition from a single pot to a
      multiphase high-shear granulation process did not seem to raise difficulties; the
      same formulations were out of specification for both processes and other trials,
      the technological properties were maintained or improved in the Fielder/Niro
      equipment.

PMID- 20818965
TI  - Preparation of fenofibrate immediate-release tablets involving wet grinding for
      improved bioavailability.
AB  - OBJECTIVE: The purpose of this study was to investigate the dissolution and oral
      bioavailability of an immediate-release tablet involving wet grinding of a poorly
      water-soluble drug, fenofibrate. METHODS: The milled suspension was prepared
      using a Basket Dispersing Mill in the presence of a hydrophilic polymer solution
      and then granulated with common excipients, and compressed into an immediate
      release tablet with blank microcrystalline cellulose granules. RESULTS: Compared
      with unmilled tablets (56% within 30 minutes), the dissolution of wet-milled
      tablets (about 98% in 30 minutes) was markedly enhanced. No significant decrease
      in the dissolution rate (96% in 30 minutes) of the wet-milled tablet was observed
      after 3 months under 40 degrees C and 75% relative humidity storage. In addition,
      the oral bioavailability of the wet-milled tablets (test) and Lipanthyl supra
      bioavailability tablets (reference) was determined in beagle dogs after a single
      dose (160 mg fenofibrate) in a randomized crossover, own-control study. The
      results suggested that both the area under the plasma concentration-time curve
      (AUC((0-t)) = 46.83 +/- 11.09 microg/mL h) and the mean peak concentration of the
      test (C(max) = 4.63 +/- 1.71 microg/mL) were higher than the reference (AUC((0
      t)) = 35.12 +/- 10.97 microg/mL h, C(max) = 2.11 +/- 0.08 microg/mL). The
      relative bioavailability of the wet-milled tablet was approximately 1.3-fold
      higher. Furthermore, the apparent rate of absorption of fenofibrate from the wet
      milled tablet (T(max) = 2.63 hours) was faster than that from Lipanthyl (T(max) =
      3.75 hours). CONCLUSION: These results indicated that the dissolution and the
      bioavailability of fenofibrate were significantly enhanced by wet-grinding
      process. So, this shows that wet grinding is a powerful technique to improve the
      bioavailability for poorly water-soluble drugs, especially for Biopharmaceutics
      Classification System Class II compounds.

PMID- 20818966
TI  - The reliability of methionine challenge test is not affected by a deficiency in
      pyridoxal phosphate, folic acid, or cobalamin.
AB  - Abnormal methionine challenge test results cannot be explained by a deficiency in
      pyridoxal phosphate, folic acid, or cobalamin. The methionine challenge test is
      reliable for demonstrating hyperhomocysteinemia. OBJECTIVE: To research the
      status of pyridoxal phosphate, folic acid, and cobalamin as part of an
      examination for hyperhomocysteinemia and to establish their relationship to the
      results of methionine challenge tests in women, who were tested at least 3 months
      after they had ended a pregnancy which was complicated by preeclampsia or other
      vascular-related pregnancy complications. METHODS: In the Isala clinics in
      Zwolle, women with vascular-related complications of pregnancy were tested at
      least 3 months postpartum for hyperhomocysteinemia, by performing a methionine
      challenge test, as well as tests to measure their vitamin status. The diagnosis
      of hyperhomocysteinemia was made after two abnormal test results. The chi(2) test
      was used to compare the vitamin status of the group with normal results to those
      with an abnormal result of methionine challenge tests. RESULTS: No statistically
      significant differences in the vitamin status were found between the group of
      women with an abnormal and the group with normal results of the methionine
      challenge tests. CONCLUSION: Abnormal methionine challenge test results cannot be
      explained by a deficiency in pyridoxal phosphate, folic acid, or cobalamin. We
      demonstrate that, when women are tested 3 months postpartum, the methionine
      challenge test is reliable for demonstrating hyperhomocysteinemia as a risk
      factor for vascular-related complications of pregnancy.

PMID- 20818967
TI  - Phosphodiesterase inhibitor effect on small artery function in preeclampsia.
AB  - OBJECTIVE: To determine if the phosphodiesterase type 5 inhibitor, sildenafil
      citrate improves endothelial-dependent relaxation of small arteries from women
      with preeclampsia. METHODS: Myometrial and omental biopsies were taken from women
      participating in a randomized placebo-controlled trial using sildenafil citrate
      in women with preeclampsia. Vasoconstriction and endothelial-dependent relaxation
      of small arteries was measured utilizing wire myography. RESULTS:
      Vasoconstriction and endothelial-dependent relaxation of myometrial and omental
      arteries were not altered in women taking sildenafil. CONCLUSION: Acute effects
      may have been lost as sildenafil administration occurred many hours prior to
      myography. Plasma sildenafil levels may have been lower than required for
      vascular response.

PMID- 20818968
TI  - Preferences for postpartum lifestyle counseling among women sharing an increased
      cardiovascular and metabolic risk: a focus group study.
AB  - OBJECTIVE: To describe women's preferences for postpartum lifestyle counseling
      after a pregnancy complicated by preeclampsia, intrauterine growth restriction,
      and/or gestational diabetes. METHODS: Thirty-six women who had experienced these
      pregnancy complications participated in six focus group interviews. RESULTS: All
      women expressed a need for participation in postpartum lifestyle counseling. They
      preferred participation to be tailored to individual preferences. A combination
      of face-to-face counseling supported by computer-tailored lifestyle advice
      appealed to them. CONCLUSION: Postpartum lifestyle counseling aimed at these
      women should be tailored to individual needs and preferences.

PMID- 20818969
TI  - Coronary stenting after myocardial infarction during twin pregnancy--a case
      report.
AB  - OBJECTIVE: We report the case of a 46-year-old woman presenting with acute chest
      pain in the 20th week of a twin pregnancy after oocyte donation. CASE REPORT: The
      Patient's medical history comprised several cardiovascular risk factors, such as
      hypertension, obesity, hypercholesterolemia, smoking, and a positive family
      history. After diagnosis of myocardial infarction, coronary catheterization and
      stenting was performed. Ten weeks later, Cesarean was indicated because of severe
      superimposed preeclampsia with lung edema. Mother and babies recovered
      uneventfully. CONCLUSION: In respect to increasing rates of higher maternal age
      and obesity during pregnancy, more attention to maternal health is required,
      particularly in programs for assisted reproductive techniques.

PMID- 20818971
TI  - Interpretation of Mendelian randomization studies and the search for causal
      pathways in atherothrombosis: the need for caution.

PMID- 20818972
TI  - The effect of features of the metabolic syndrome on atherosclerotic risk in
      relatively long-surviving patients with type 1 diabetes.
AB  - BACKGROUND: Increasing numbers of patients with type 1 diabetes (T1DM) are
      developing features of the metabolic syndrome. The additional effect of this on
      the development of atherosclerosis, as inferred by the carotid artery intima
      media thickness (IMT), has not previously been assessed. The aim of this study
      was to assess the effect of features of the metabolic syndrome on carotid artery
      IMT in a cohort of long-surviving patients with T1DM. METHODS: Long-surviving
      patients with T1DM attending the Centre for Diabetes and Endocrinology were
      assessed regarding their risk factor profile. All underwent measurement of
      carotid artery IMT. In all, 156 patients who had T1DM for more than 18 years had
      their carotid artery IMT measured. All had been attending the clinic for over 10
      years, and past clinical and laboratory records were available. RESULTS: A total
      of 37 patients had metabolic syndrome according to the International Diabetes
      Federation (IDF) definition. Those with metabolic syndrome had a significantly
      increased carotid artery IMT (P = 0.003) compared to those without the syndrome.
      There was a significant relationship between the number of features of metabolic
      syndrome and increased atherosclerotic risk according to the carotid artery IMT
      (P = 0.01). A significant correlation was found between carotid artery IMT and
      both waist circumference (P < 0.001) and insulin resistance (P = 0.005).
      CONCLUSIONS: In long-surviving patients with T1DM, those that develop metabolic
      syndrome are more likely to have thicker carotid artery IMT, and, by inference,
      be at higher risk of atherosclerosis and possibly cardiovascular disease. A
      linear relationship was present between both waist circumference and insulin
      resistance and carotid artery IMT.

PMID- 20818974
TI  - Risk factors for microvascular complications of diabetes among South Indian
      subjects with type 2 diabetes--the Chennai Urban Rural Epidemiology Study (CURES)
      Eye Study-5.
AB  - BACKGROUND: This study assessed the relationship between and risk factors for
      microvascular complications of diabetes in an urban South Indian type 2 diabetes
      population. METHODS: Subjects with diabetes (n = 1,736) were selected from the
      population-based Chennai Urban Rural Epidemiology Study (CURES) Eye Study
      conducted on a representative population of Chennai city in south India. Four
      field stereo retinal color photography was done, and diabetic retinopathy (DR)
      was classified according to the Early Treatment DR Study grading system.
      Neuropathy was diagnosed if the vibratory perception threshold of the big toe
      using biothesiometry was >= 20V. Overt nephropathy was diagnosed if the subjects
      had persistent macroalbuminuria (urinary albumin excretion >= 300 MUg/mg of
      creatinine) and microalbuminuria if it was between 30 and 299 MUg/mg of
      creatinine. Among the 1,715 subjects with gradable fundus photographs, 1,608
      individuals who had information on all test parameters were included. RESULTS:
      Overall, DR was present in 282 (17.5%), neuropathy in 414 (25.7%), overt
      nephropathy in 82 (5.1%), and microalbuminuria in 426 (26.5%) subjects. Eighteen
      subjects had all three microvascular complications of diabetes. The risk of
      nephropathy (odds ratio [OR] = 5.3, P<0.0001) and neuropathy (OR = 2.9, P<0.0001)
      was significantly higher among the subjects with sight-threatening DR compared to
      those without DR. Common risk factors identified for all the three microvascular
      complications of diabetes were age, glycated hemoglobin, duration of diabetes,
      and serum triglycerides. DR was associated with nephropathy after adjusting for
      age, gender, hemoglobin A1c, systolic blood pressure, serum triglycerides, and
      duration of diabetes (OR = 2.140, 95% confidence interval = 1.261-3.632, P =
      0.005). CONCLUSIONS: This is the first population-based study from India to
      report on all microvascular complications of diabetes and reveals that the
      association between DR and nephropathy is stronger than that with neuropathy.

PMID- 20818975
TI  - Antiproliferative activity of N6-isopentenyladenosine on MCF-7 breast cancer
      cells: cell cycle analysis and DNA-binding study.
AB  - N(6)-Isopentenyladenosine (iPA) is a member of the cytokinins, a family of plant
      hormones that regulate plant cell growth and differentiation. iPA is present in
      mammalian cells in a free form, as a mononucleotide in the cytoplasm, or in a
      tRNA-bound form. Its antiproliferative activity against cancer cells lines has
      been reported by several authors. We show that iPA inhibits the growth of human
      breast cancer MCF-7 cells in a dose-dependent manner with a concentration of 12.2
      MUM, which causes 50% inhibition of cell viability. The cell cycle analysis by
      flow cytometry showed that iPA-induced growth arrest could be associated to
      apoptosis. The interaction of DNA with iPA was studied in aqueous solution at
      physiological conditions by ultraviolet-vis spectroscopy. A binding constant
      K(iPA-DNA) = 4.4 * 10(3) M(-1) was calculated and this value, together with the
      shift of absorbance, suggests iPA-DNA interaction at DNA surface.

PMID- 20818976
TI  - Genetic alterations of the LKB1 gene in head and neck cancer.
AB  - The genetic alterations associated with head and neck cancer (HNC) are numerous
      and include a variety of different pathways. It has also been shown that numerous
      tumor suppressor genes are involved in HNC. The LKB1 gene has been defined as a
      tumor suppressor gene, and somatic mutations of this gene have been identified in
      many different neoplasms. The aim of this study was to investigate the LKB1 gene
      in HNC. Nine exons of the LKB1 gene were analyzed by direct sequencing. We
      detected a novel missense mutation in the nuclear localization signal coding
      region of the LKB1 gene in 10 tumor samples from patients with HNC. Six different
      single-nucleotide substitutions were also observed in the introns. In two
      patients, a 7 bp duplication was detected in intron 3. These results indicate
      that the LKB1 gene may play a role in the etiology of HNC.

PMID- 20818977
TI  - Effect of subcutaneous glucose sensor implantation on skin mRNA expression in
      pigs.
AB  - BACKGROUND: Tight glycemic control has the potential to reduce long- and short
      term effects of diabetes mellitus. New and improved glucose sensors for short
      term implantation in the subcutis offer an alternative to the classical self
      monitored blood glucose concentration in the management of diabetes. The use of
      glucose sensors has an advantage over the latter due to its capacity to obtain
      continuous glucose measurements. However, instability of in vivo glucose sensor
      measurements has been reported, and this bioinstability is likely to be
      influenced by the inflammatory reaction to the implanted sensor. Gene expression
      analysis is now performed in an existing porcine model of subcutaneous glucose
      sensor implantation to investigate the time course of inflammation from a new
      perspective. METHODS: Tissue surrounding glucose sensors was sampled to different
      time points (2 h, 24 h, 3 days, and 7 days) after implantation in the subcutis of
      pigs. From the tissue RNA was extracted, cDNA was synthesized, and real-time
      reverse transcription-polymerase chain reaction (RT-PCR) was performed for the
      quantification of immunoregulatory genes. RESULTS: Genes coding for adhesion
      molecules, chemokines, cytokines, CD markers, and antigen presentation molecules
      were differentially expressed over time. Most of the investigated genes were
      significantly up-regulated 24 h and 7 days after implantation. CONCLUSIONS: The
      present study demonstrated that the technology for targeted multiple-gene
      expression by real-time RT-PCR is useful in the evaluation of the immune response
      to subcutaneously implanted glucose sensors and that the expression levels also
      seemed to correspond to the histomorphological observations over time.

PMID- 20818978
TI  - A gradient of NOS1 overproduction alleles in European and Mediterranean
      populations.
AB  - AIM: A (CA)n repeat located in the 3' UTR region of exon 29 of the NOS1 gene
      (encoding for neuronal nitric oxide synthase) has been shown to affect the size
      of mRNA. NOS1 mRNA is highly diverse, contributing to changes in transcript
      generation, degradation, processing, or subcellular targeting. In the present
      work, we analyzed allele frequencies of this (CA)n repeat in nine populations of
      the Mediterranean area and Middle Europe. We aimed at testing the presence of a
      north-south positive gradient of frequencies of <=17 allele repeats, compatible
      with the hypothesis of positive selection suggested in two of our previous works,
      related to the past prevalence of malaria infection in Europe. RESULTS: Results
      show significant negative correlations of latitude with frequencies of alleles S
      and genotypes S/S and S/L (p < 0.01). CONCLUSIONS: In conclusion, the north-south
      gradient of S alleles found in the present work would confirm our previous
      observation about the NOS1 gene, reinforcing the hypothesis of a selective action
      of malaria infection. This hypothesis is strengthened by the role of nitric oxide
      in the immunity system.

PMID- 20818979
TI  - Analysis of azoospermia factor loci polymorphisms among Tunisian infertile men
      with varicocele.
AB  - AIMS: The preponderance of experimental data from clinical and animal models
      demonstrates an adverse effect of varicocele on spermatogenesis. The review of
      the literature shows that there may be an underlying genetic etiology in
      varicocele. Here, we explore the Yq microdeletions among infertile men to
      evaluate their involvement in varicocele development and sperm production defect.
      RESULTS: Microdeletions of 14 sequence-tagged-sites in the Yq11 region were
      screened in 210 infertile men using polymerase chain reaction techniques. Out of
      210 infertile men, 69 (33%) men were with varicocele. Our results showed that the
      risk to develop varicocele is increased among infertile men with spermatogenesis
      (oligo-normospermia) (odds ratio = 3.57, confidence interval 95%: 1.49-8.84).
      However, we did not find any relationship between Y chromosome microdeletions and
      varicocele appearance (p = 0.73). In addition, a significant association was
      found between Y microdeletions and oligospermia (p < 10(-8)) or azoospermia (p <
      10(-8)) using patients with normospermic characteristics as a control.
      CONCLUSION: Our work showed the absence of relationship between Y chromosome
      microdeletions and varicocele development and the association of the two factors,
      independently, with sperm production defect.

PMID- 20818980
TI  - The role of plasminogen activator inhibitor-1 and angiotensin-converting enzyme
      gene polymorphisms in bronchopulmonary dysplasia.
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) is a multifactorial disease of
      preterm infants that is characterized by airway injury, inflammation, and
      parencymal remodeling. Activation of the coagulation cascade leads to
      intraalveolar fibrin deposition in many inflammatory pulmonary disorders.
      Increased fibrin formation or decreased fibrinolysis may cause extravascular
      fibrin deposition. Extravascular fibrin deposits in septae and alveoli due to the
      altered fibrin turnover are the pathological hallmarks of BPD, which strongly
      indicate the importance of the imbalance in the competing activities of
      coagulation and fibrinolysis. OBJECTIVE: We investigated the predictive value of
      variations in plasminogen activator inhibitor-1 (PAI-1) and angiotensin
      converting enzyme (ACE) genes as molecular determinants for BPD in neonates.
      METHODS: The study group comprised 98 preterm infants with BPD and a control
      group including 94 preterm infants without BPD. Restriction fragment size
      analyses were performed by visualizing digested polymerase chain reaction
      products for ACE and PAI-1 genotypes. RESULTS: No significant associations were
      found between ACE, PAI-1 gene polymorphisms, and BPD phenotype in our population.
      CONCLUSIONS: The two gene polymorphisms (PAI-1 and ACE) had no role in the
      development of BPD in our study. Further studies with other genes are required
      for the identification of molecular predisposing factors for BPD that may help in
      the development of new treatments.

PMID- 20818981
TI  - The role of polyphenolic antioxidants in health, disease, and aging.
AB  - Polyphenolic antioxidants from dietary sources are frequently a topic of interest
      due to widespread scientific agreement that they may help lower the incidence of
      certain cancers, cardiovascular and neurodegenerative diseases, and DNA damage
      and even may have antiaging properties. On the other hand, questions still remain
      as to whether some antioxidants could be potentially harmful to health, because
      an increase in glycation-mediated protein damage (carbonyl stress) has been
      reported in some cases. Nevertheless, the quest for healthy aging has led to the
      extensive use of phytochemically derived antioxidants to disrupt age-associated
      deterioration in physiological function and to prevent many age-related diseases.
      Although a diet rich in the polyphenolic forms of antioxidants does seem to offer
      hope in delaying the onset of age-related disorders, it is still too early to
      define their exact clinical benefit for treating age-related disease. This review
      critically examines polyphenolic antioxidants, such as flavonoids, curcumene, and
      resveratrol in health, disease, and aging with the hope that a better
      understanding of the many mechanisms involved with these diverse compounds may
      lead to better health and novel treatment approaches for age-related diseases.

PMID- 20818982
TI  - In the light of the metabolic memory theory, should not all aged people with
      dysglycemia be treated?
AB  - Dysglycemia has been coined to define the prediabetic state. It defines high
      glucose levels below the diabetes "cut-offs." The negative effects of
      dysglycemia, leading to cardiovascular complications, are amplified during aging.
      Despite this knowledge, treatment of dysglycemia in old subjects is usually
      overlooked by clinical practice. This article deals with a new theory regarding
      an intensive therapeutic approach targeting aged people. This hypothesis arises
      from the recent theory of metabolic memory, which defines early imprinting due to
      hyperglycemia in cells of the vasculature and of target organs, favoring the
      development of vascular complications. In addition, metabolic memory determines a
      durable effect of hypoglycemic treatment that is much longer than the period of
      therapy. This new evidence could allow us to hypothesize that a treatment of
      dysglycemia in aged people could remodel their glucose "trajectory" during aging
      toward a more optimal one, leading to successful aging.

PMID- 20818983
TI  - Biochanin A reduces drug-induced p75NTR expression and enhances cell survival: a
      new in vitro assay for screening inhibitors of p75NTR expression.
AB  - Following spinal cord injury (SCI) or peripheral neuropathy, increased levels of
      the p75(NTR) death receptor initiate the signal transduction cascade leading to
      cell death. Investigations of compounds that may ameliorate neuronal cell death
      have largely used rodent models, which are time consuming, expensive, and
      cumbersome to perform. Previous studies had demonstrated that steroids,
      particularly dexamethasone and its analog methylprednisolone sodium succinate,
      exhibit limited neuroprotective effects against neuronal injury. Significantly,
      many naturally occurring nonsteroidal plant compounds exhibit structural overlap
      with steroids. In this report, we present an in vitro cellular screen model to
      practically examine the efficacy of various phytoestrogens in modulating the
      ibuprofen-induced expression of p75(NTR) and reduced cell survival of CCFSTTG1
      and U87MG cells in a rescue (postinjury) or prevention (preinjury) regimen. We
      show that the phytoestrogen, biochanin A, and, to a lesser extent, genistein are
      more effective than dexamethasone at reducing p75(NTR) expression and improving
      the viability of U87MG and CCFSTTG1 before and after p75(NTR) induction.
      Furthermore, these studies implicate biochanin A's inactivation of p38-MAPK as a
      possible contributor to reducing p75(NTR) with associated increased cell
      survival. This new in vitro assay facilitates a more time-efficient screening of
      compounds to suppress p75(NTR) expression and increase neuronal cell viability
      prior to their evaluation in animal models of neurological diseases.

PMID- 20818984
TI  - Empiric, broad-spectrum antibiotic therapy with an aggressive de-escalation
      strategy does not induce gram-negative pathogen resistance in ventilator
      associated pneumonia.
AB  - BACKGROUND: Early, empiric, broad-spectrum antibiotics followed by de-escalation
      to pathogen-specific therapy is the standard of care for ventilator-associated
      pneumonia (VAP). In our surgical intensive care unit (SICU), imipenem-cilastatin
      (I-C) in combination with tobramycin (TOB) or levofloxacin (LEV) has been used
      until quantitative bronchoalveolar lavage results are finalized, at which time de
      escalation occurs to pathogen-specific agents. With this practice, however,
      alterations in antimicrobial resistance remain a concern. Our hypothesis was that
      this strict regimen does not alter antimicrobial susceptibility of common gram
      negative VAP pathogens in our SICU. METHODS: After Institutional Review Board
      approval, a retrospective review of SICU-specific antibiograms was performed for
      the sensitivities of common gram-negative VAP pathogens. Time periods were
      defined as early (January-June 2005) and late (July-December 2006). Chart review
      of empiric and de-escalation antibiotic usage was obtained. Data were collated,
      and statistical significance was assessed with the chi-square test using the on
      line Simple Interactive Statistical Analysis tool. RESULTS: Imipenem-cilastatin
      was used 198 times for empiric VAP coverage (811 patient-days), whereas TOB and
      LEV were given a total of 149 (564 patient-days) and 61 (320 patient-days) times,
      respectively. Collectively, the susceptibility of gram-negative organisms to I-C
      did not change (early 91.4%; late 97%; p = 0.33). Individually, non-significant
      trends to greater sensitivity to I-C were noted for both Pseudomonas aeruginosa
      (early 85.7%; late 90.9%; p = 0.73) and Acinetobacter baumannii (early 80%; late
      100%; p = 0.13). Further, both TOB (early 77.1%; late 70.0%; p = 0.49) and LEV
      (early 74.3%; late 70.0%; p = 0.67) were found to maintain their susceptibility
      profiles. The frequency of resistant gram-positive VAPs was unchanged during the
      study period. Our de-escalation compliance (by 96 h) was 78% for I-C, 77.2% for
      TOB, and 59% for LEV. When infections requiring I-C were removed from the
      analysis, de-escalation compliance was improved to 92%. CONCLUSIONS: In our SICU,
      early, empiric broad-spectrum VAP therapy followed by de-escalation to pathogen
      specific agents did not alter antimicrobial resistance and is a valid practice.
      Further, our compliance with de-escalation practices was higher than published
      rates.

PMID- 20818985
TI  - Percutaneous radiofrequency ablation does not affect glomerular filtration rate.
AB  - PURPOSE: To study short- and intermediate-term global renal function in patients
      undergoing a single percutaneous radiofrequency ablation (pRFA) for a solitary
      renal parenchymal tumor. MATERIALS AND METHODS: We reviewed the records of 62
      patients who underwent a single pRFA for solitary renal parenchymal tumor. We
      used the abbreviated Modified Diet for Renal Disease equation to calculate
      baseline, 1-month, and 1-year glomerular filtration rate (GFR). We defined normal
      as >60, moderately diminished as 45-60, and severely diminished GFR as <45
      cc/minute/1.73 m2. We used the Wilcoxon paired rank sum method to compare 1-month
      and 1-year GFR to baseline. We fit a linear regression model to test the
      association of lesion size to GFR controlling for lesion location and baseline
      GFR. RESULTS: There was no difference in GFR from baseline at 1 month or 1 year
      (55 vs. 58 cc/minute/1.73 m2, p=0.24 and 55 vs. 57 cc/minute/1.73 m2, p=0.8,
      respectively). Tumor size did not affect GFR at 1 month or 1 year after
      controlling for lesion location and baseline GFR. CONCLUSIONS: A single
      application of pRFA does not affect GFR in the short or intermediate term.

PMID- 20818986
TI  - Use of an angiographic catheter to facilitate fluoroscopy-guided percutaneous
      renal access in cases with diffuse contrast extravasation.
AB  - PURPOSE: Occasionally during percutaneous surgery, significant contrast
      extravasation obscures the field, making fluoroscopic access no longer feasible.
      Herein, we describe a salvage technique. MATERIALS AND METHODS: The
      cystoscopically placed, open-end ureteral catheter is exchanged with an angled
      tip angiographic catheter. With the aid of a guidewire and under fluoroscopic
      guidance, the tip of the catheter is placed in a posterior calix. The "bull's
      eye" technique is then applied to direct the needle into the tip of the catheter.
      This technique was used in four cases over a 7-year period. RESULTS: Successful
      access was accomplished in all cases through a middle or upper calix. CONCLUSION:
      The catheter serves as a target for providing access to the renal collecting
      system and facilitates final tract dilatation.

PMID- 20818987
TI  - A decade of surgically removed small renal masses in the Netherlands:
      characteristics and trends in type of surgery and pathologic reporting.
AB  - PURPOSE: To assess nationwide the pathologic characteristics and trends in type
      of surgery and pathologic reporting in surgically managed renal tumors <= 4 cm.
      MATERIALS AND METHODS: A review of all pathologic reports of primary small renal
      masses operated on in the Netherlands during the period 1995 to 2005 was
      performed. The data source was a nationwide central archive of histocytopathology
      (Patologisch Anatomisch Landelijk Geautomatiseerde Archief). Tumors were
      stratified into three groups: <= 2, 2.1 to 3.0, and 3.1 to 4.0 cm. Age, sex, type
      of operation, and tumor pathology were analyzed. For renal-cell carcinomas, grade
      (3-tiers Fuhrman) and stage (2002 Tumor, Node, Metastasis) were assessed. Trends
      in type of surgery (radical or partial nephrectomy [PN]) and pathologic reporting
      during the study period were analyzed. RESULTS: Of all operated primary kidney
      tumors, 25.3% were <= 4.0 cm. The mean age of the patients was 63.1 years
      (standard deviation 11.7), and the male/female ratio was 3:2. Only 7.5% were
      benign tumors, and 9.8% were locally advanced (>= T3). Tumors <= 3.0 cm were more
      likely to be benign (P = 0.006) and of lower stage (P <= 0.001) than tumors of
      3.1 to 4 cm. PN was performed in 16.5% of the cases. Grade and subtype were
      reported in 55% of the cases. The rate of PNs performed increased during the
      decade. There was a trend in increased reporting of grade and subtype.
      CONCLUSIONS: A quarter of all the operated primary kidney tumors were <= 4 cm.
      Smaller tumors were more likely to be benign and of lower stage. A cutoff size
      regarding biologic aggressiveness can be settled at the 3 cm size. The PN rate
      increased along the decade. Grade and subtype reporting rates remained
      suboptimal, although a positive trend was noted.

PMID- 20818988
TI  - Use of a novel absorbable barbed plastic surgical suture enables a "self
      cinching" technique of vesicourethral anastomosis during robot-assisted
      prostatectomy and improves anastomotic times.
AB  - PURPOSE: To demonstrate a novel technique of self-cinching anastomosis using a
      barbed and looped suture during robot-assisted radical prostatectomy (RARP).
      PATIENTS AND METHODS: This is a feasibility study of 50 consecutive patients who
      underwent this novel self-cinching anastomotic technique using a V-LocTM 180
      absorbable barbed suture after RARP for clinically localized prostate cancer. The
      results were then compared with 50 consecutive patients who underwent RARP by the
      same surgeon before this new technique. We examined whether this novel technique
      had any effects on posterior reconstruction time, vesicourethral anastomosis
      time, and thus total reconstruction and operative time by inference. RESULTS: The
      V-Loc 180 group had significantly shorter posterior reconstruction (40 seconds vs
      60 seconds; P <= 0.001) and vesicourethral anastomotic times (7 min vs 12 min; P
      <= 0.001). By inference, this meant that total reconstruction and operative times
      were also significantly less (8 minutes vs 13.5 min; P <= 0.001 and 106 min vs
      114.5 minutes; P <= 0.001, respectively). CONCLUSION: We have shown that this
      technique is feasible and improves posterior reconstruction and anastomotic
      times. Further follow-up will determine any benefits of this technique on
      anastomotic urinary leak rates, continence, and catheter removal times.

PMID- 20818989
TI  - Nephrolithiasis in autosomal dominant polycystic kidney disease.
AB  - BACKGROUND AND PURPOSE: Autosomal dominant polycystic kidney disease (ADPKD)
      manifests with renal and extrarenal abnormalities and is inherited in an
      autosomal dominant fashion. In addition to multiple renal cysts, abnormalities
      such as liver cysts (80%), pancreatic cysts, splenic cysts, pulmonary cysts,
      berry aneurysms in the distribution of arterial circle of Willis (8%), colonic
      diverticula, mitral valve prolapse, etc., can be present. The condition will
      develop in half of the offspring of affected persons because of its 100%
      penetrance. Nephrolithiasis in patients with ADPKD is not infrequent and, given
      the importance of preservation of renal function in this subset of patients, a
      clear understanding of the management options available and their advantages and
      disadvantages is absolutely essential and critical in better patient outcomes.
      This article is an endeavor in this direction and provides a review of the
      current available literature. MATERIALS AND METHODS: An electronic database
      search of Medline, Embase, and Cochrane library was performed to search for the
      available literature in January 2010 with no restrictions in terms of date or
      language. The search terms used were ADPKD, nephrolithiasis, percutaneous
      nephrolithotomy, shockwave lithotripsy, flexible ureterorenoscopy, congenital
      kidney disorders, etc., separately and in various combinations. The articles so
      extracted were scrutinized for relevance and selected for the review.

PMID- 20818990
TI  - Comparative analysis of global practice patterns in urologic robot-assisted
      surgery.
AB  - OBJECTIVES: To determine and compare the status of urologic laparoscopic and
      robot-assisted surgery (RAS) across the world. METHODS: Two hundred ninety-one
      surveys were completed by urologists at various national and international
      conferences in 2008. The 58-item questionnaire assessed the individual and
      institutional practice patterns of minimally invasive surgery with a focus on
      RAS. Surveys from Europe and North American continents (ENA) were compared with
      surveys from the Middle East and Asian continents (MEA). RESULTS: One hundred
      sixty-six (57%) surveys were completed by urologists from MEA and 125 (43%) from
      ENA. Eighty percent of respondents performed minimally invasive surgery, with 64%
      having prior formal training. Respondents in ENA were more likely to have had
      formal training in RAS and performed more RAS cases (p < 0.01). Sixty percent of
      those surveyed from ENA had used robotic consoles in training courses compared
      with only 20% in MEA (p < 0.01). Dedicated RAS support teams were less common in
      MEA (p < 0.01). Lack of a robotic system was the most common deterrent for RAS in
      MEA (56%). Respondents in ENA performed more robot-assisted radical
      prostatectomy, robot-assisted radical cystectomy, and robot-assisted nephrectomy.
      In the more established robotic environment of ENA, robot-assisted radical
      prostatectomy, robot-assisted radical cystectomy, and robot-assisted nephrectomy
      represented the gold standard in 34%, 14%, and 26% of surveys, respectively.
      Comparatively, MEA respondents were more likely to believe RAS represented the
      gold standard. CONCLUSIONS: Usage of RAS in urology continues to grow across the
      globe, though to most it represents a surgical alternative rather than benchmark.
      Even with reduced exposure, training, and access, more urologists in the MEA
      considered RAS to be the surgical standard for prostatectomy, cystectomy, and
      nephrectomy. The evolution of attitudinal change should be the focus of further
      study.

PMID- 20818991
TI  - Laparoscopic simultaneous bilateral dismembered pediatric pyeloplasty applying
      three midline ports.
AB  - OBJECTIVES: The objective of this study was to describe our experience with
      laparoscopic simultaneous bilateral dismembered pyeloplasty in two pediatric
      cases by using three midline ports. METHODS: A 5-year-old boy and a 5-month-old
      male infant with bilateral ureteropelvic junction obstruction underwent bilateral
      laparoscopic transperitoneal dismembered pyeloplasty. A 10-mm trocar was placed
      through the umbilicus, and two 5-mm trocars were also placed in the midline
      superior and inferior to the umbilicus. On the left side, dismembered pyeloplasty
      was performed through a transmesocolic approach. Double-J ureteral stent was
      inserted through one of the trocars on both sides. RESULTS: The postoperative
      period was uneventful. Patients were discharged on postoperative days 4 and 5.
      Oral feeding was tolerated on the first postoperative day. In a 6-month follow-up
      period, excretory urography and renal scan showed resolution of obstruction.
      CONCLUSIONS: Laparoscopic dismembered pyeloplasty can be performed in a single
      session for pediatric patients with bilateral ureteropelvic junction obstruction.
      This can obviate the need for two sessions of anesthesia induction and
      intubation. However, more studies with large number of patients are needed to
      confirm this result.

PMID- 20818992
TI  - Confirmation of germ-line transmission in the red fluorescence protein (RFP)
      transgenic cloned male cat.
AB  - The production of transgenic animals is highly desirable for biotechnology and
      basic research. We investigated the reproductive ability of a red fluorescence
      protein (RFP) transgenic cloned male cat (RFP TG cat) by natural mating with a
      domestic female cat. The RFP expression levels were examined in early
      embryogenesis, tissues from 45-day-old two fetuses, and four RFP TG cat
      offspring. The RFP gene was detected in tissue samples from one dead kitten,
      including several organs and the skin. Also, under a fluorescent light source, we
      were able to directly detect the RFP expression of in in vitro-produced
      blastocysts derived with sperm from the RFP TG cat. These results indicate that
      the RFP TG cat exhibits normal reproductive fertility, stable germ-line
      transmission of the RFP transgene, and characteristic RFP expression in its
      offspring. We isolated feline neural progenitor cells from a 45-day-old fetus
      derived from the natural mating of the RFP TG cat with a domestic female cat.
      Isolated brain and retinal progenitor cells were successfully passaged at least
      four times post isolation (day 23), and showed a high RFP expression level. This
      method of producing genetically modified cloned cats will be important for
      generating biomedical models of human diseases.

PMID- 20818993
TI  - Epigenetic differences between embryonic stem cells generated from blastocysts
      developed in vitro and in vivo.
AB  - Embryonic stem (ES) cells constitute a very important tool for regenerative
      medicine today. These ES cells, and human ES cells in particular, are almost all
      derived from embryos obtained by in vitro fertilization (IVF) and from in vitro
      culture (IVC); however, such in vitro manipulated embryos often show abnormal
      genomic imprinting, which can lead to the development of various diseases.
      Nevertheless, several reports have evaluated ES cells derived from in vitro
      manipulated embryos. In this study, we established ES cells derived from both in
      vivo and in vitro developed blastocysts (Vivo ES cells and Vitro ES cells,
      respectively) to compare the methylation status of imprinted genes and gene
      expression patterns. At very early passages, Vitro ES cells showed an increase in
      abnormal genomic imprinting compared to Vivo ES cells. In addition, we found that
      the gene expression patterns of several methylation related-genes frequently
      shifted to promote demethylation and to inhibit methylation in early-passage
      Vitro ES cells. In contrast, at later passages, we found no significant
      differences between Vivo and Vitro ES cells. In conclusion, it is advisable to
      use early passage Vivo ES cells whenever feasible, or to select ES cell lines
      with a normal epigenotype.

PMID- 20818994
TI  - Hand-made cloned goat (Capra hircus) embryos-a comparison of different donor
      cells and culture systems.
AB  - Nuclear transfer is a very effective method for propagation of valuable, extinct,
      and endangered animals. Hand-made cloning (HMC) is an efficient alternative to
      the conventional micromanipulator-based technique in some domestic species. The
      present study was carried out for the selection of suitable somatic cells as a
      nuclear donor and development of an optimum culture system for in vitro culture
      of zona-free goat cloned embryos. Cleavage and blastocyst rates were observed
      72.06 +/- 2.94% and 0% for fresh cumulus cells, 81.95 +/- 3.40% and 12.74 +/-
      2.12% for cultured cumulus cells, and 92.94 +/- 0.91% and 23.78 +/- 3.33% for
      fetal fibroblast cells, respectively. There was a significant (p < 0.05) increase
      in blastocyst production in goats when cultured on a flat surface (FS) (23.78 +/-
      3.33 %) than well of wells (WOW) (15.84 +/- 2.12 %) and microdrops (MD) (0.7 +/-
      0.7%). Furthermore, cleavage and blastocyst production rates were significantly
      (p < 0.05) more in the WOW (15.84 +/- 2.12%) than the MD (0.7 +/- 0.7%) system.
      The quality of HMC blastocysts was studied by differential staining. Genetic
      similarity was confirmed by polymerase chain reaction (PCR)-based amplification
      of the second exon of the MHC class II DRB gene, which gave similar bands in
      electrophoresis (286 bp) both in cloned embryos and donor cells. In conclusion,
      the present study describes that the fetal fibroblast cell is a suitable
      candidate as nuclear donor, and the flat surface culture system is suitable for
      zona-free blastocyst development by the hand-made cloning technique in the goat.

PMID- 20818995
TI  - Joint effects of topoisomerase alterations and plasmid-mediated quinolone
      resistant determinants in Salmonella enterica Typhimurium.
AB  - Alterations in topoisomerases and plasmid-mediated quinolone-resistant (PMQR)
      determinants have been identified as main quinolone-resistant mechanisms in
      Salmonella enterica Typhimurium. But the joint effects of these mechanisms have
      not been thoroughly characterized in homologous Salmonella Typhimurium strains.
      In this study, isogenic topoisomerase mutants were constructed using phage lambda
      Red recombinase system and phage transduction. And the joint effects of
      topoisomerase mutations (gyrA [S83F], gyrA [S83F, D87N] and parC [S80I]) and PMQR
      determinants (including qnrB4, qnrS1, aac(6')-Ib-cr, and qepA) were studied in
      homologous genetic constitutions. Our data showed that mutations in gyrA played a
      dominant role in fluoroquinolone resistance in Salmonella Typhimurium and have a
      synergistic effect with other resistant mechanisms. The mutation (S80I) in parC
      would have no effect in quinolone resistance without gyrA mutations. The joint
      effect of aac(6')-Ib-cr and topoisomerase mutations were only observed for
      ciprofloxacin among tested quinolones. Different joint effects between
      topoisomerase mutations and qepA, qnrB4, or qnrS1 were observed for tested
      quinolones. Importantly, the acquirement of the PMQR determinants could improve 0
      to 32-fold of the host mutant prevention concentration to ciprofloxacin. Our
      data showed that the acquirement of PMQR determinants could not only improve the
      host minimal inhibitory concentrations to quinolones but also accelerate the
      generation of high-level fluoroquinolone-resistant mutants.

PMID- 20818996
TI  - Liquid nitrogen cryotherapy on Leishmania donovani cutaneous leishmaniasis.
AB  - OBJECTIVE: To evaluate the efficacy and the safety of liquid nitrogen cryotherapy
      (LN) on Leishmania donovani cutaneous leishmaniasis and on type V skin. METHODS:
      LN was applied to 65 patients (121 lesions) using cotton swabs attached to ekels.
      Cryosessions were performed for 15-20 seconds, two per site, weekly for 1-3
      weeks, fortnightly for 4-5 weeks and then monthly until cure. Patients were
      followed-up for 6 months after cure. RESULTS: A total of 91.7% of patients were
      cured within one to seven cryosessions; mean 3.57. With one to four cryosessions,
      papules <= 1 cm in diameter showed rapid healing (90.5%) in comparison with those
      of > 1 cm diameter (64.28%). The cure rates for lesions on the head (84.61%) and
      upper limb (82.6%) were greater than those for the lower limbs (71.42%) and trunk
      (66.66%). With LN, local pain lasted for 15-30 minutes; ulceration (33%),
      depigmentation (46.9%) and scarring (43%) were noticed. During 6 months of follow
      up there was one (1.6%) recurrence. CONCLUSIONS: LN (77.15% cure within one to
      four cryosessions) is an alternative to intralesional sodium stibogluconate in
      the treatment of papules measuring <= 1 cm. In type V skin, LN should be avoided
      on the face, and on patients who have a tendency to form keloids. We recommend
      giving cryotherapy using cryoguns (instead of cotton swabs attached to ekels)
      fortnightly (not weekly), which may minimize ulceration, and therefore scarring.

PMID- 20818997
TI  - In vivo confocal microscopy of long-standing mixed-form vernal
      keratoconjunctivitis.
AB  - PURPOSE: To report the morphological characteristics of long-term mixed-form
      vernal keratoconjunctivitis (VKC) using in vivo laser scanning confocal
      microscopy (LSCM). DESIGN: Descriptive case report. METHODS: In vivo LSCM was
      performed on a Chinese patient diagnosed as bilateral mixed-form VKC for 14
      years. Central cornea, inferior limbus, bulbar conjunctiva, and upper tarsal
      conjunctiva of both eyes were examined. RESULTS: Infiltration of numerous
      dendritic cells and inflammatory cells in both bulbar conjunctiva and tarsal
      conjunctiva were identified under in vivo LSCM, along with proliferation of
      fibrous tissue in the conjunctival stroma and damage of Vogt palisades. Apart
      from abnormal appearance of corneal epithelial cells, the infiltration of
      dendritic cells was occasionally found in the cornea. CONCLUSIONS: In vivo LSCM
      is a useful tool to evaluate the morphology of VKC.

PMID- 20818998
TI  - A microfabricated scaffold induces the spheroid formation of human bone marrow
      derived mesenchymal progenitor cells and promotes efficient adipogenic
      differentiation.
AB  - Here, we report the highly efficient in vitro differentiation of human bone
      marrow-derived mesenchymal stem/progenitor cells (MPCs) using a novel
      nanotechnology-based culture plate, nanoculture plate((r)) (NCP). The NCP
      contains uneven microfabrications with diameters of ~2-3 MUm arranged in a
      honeycomb pattern on its culture surface, which is devoid of animal-derived
      protein sources. When human MPCs were subjected to three-dimensional (3D) culture
      using an NCP, they rapidly formed adhesive spheroids. We showed that adipogenic
      differentiation in NCP-mediated 3D cultures led to more rapid accumulation of
      triglycerides than that in two-dimensional cultures. During adipogenesis in 3D
      cultures, the rapid and intense induction of adipocyte-specific gene expressions,
      such as peroxisome proliferator-activated receptor gamma (PPAR-gamma), CCAAT
      enhancer-binding protein alpha (C/EBP-alpha), adipocyte protein 2 (aP2), and
      adiponectin was observed. Together, these results indicate that this 3D culture
      system is suitable for the differentiation of human MPCs into adipogenic lineage,
      and could be applicable to adipose tissue engineering under xeno-free condition.

PMID- 20819000
TI  - Functionalization of electrospun poly(epsilon-caprolactone) fibers with the
      extracellular matrix-derived peptide GRGDS improves guidance of schwann cell
      migration and axonal growth.
AB  - The best available treatment of peripheral nerve lesions involves transplantation
      of an autologous nerve. This approach, however, entails sensory deficits at the
      donor site and requires additional surgery. Such limitations have motivated the
      search for a bioengineering solution to design artificial implants. For this
      purpose we are producing orientated biodegradable microfibers of poly(epsilon
      caprolactone) (PCL) with electrospinning. The present study describes the
      functionalization of these electrospun fibers with biologically active peptides
      to produce guidance structures for Schwann cell migration and axonal
      regeneration. For the chemical modification PCL was blended with star-shaped NCO
      poly(ethylene glycol)-stat-poly(propylene glycol) (PCL/sPEG) as a covalent linker
      for the peptide GRGDS, derived from extracellular matrix proteins. To test
      biological functions of electrospun fibers, Schwann cell migration and axonal
      growth from dorsal root ganglia explants were investigated with time lapse video
      microscopy. Migrating Schwann cells as well as growing sensory axons closely
      followed the electrospun fibers with occasional leaps between adjacent fibers.
      Cell migration was characterized by frequent changes in velocity and direction
      reversals. Comparison of substrates showed that functionalized fibers caused more
      Schwann cells to move out of the explants, supported faster cell migration and
      axonal growth than the nonfunctional fibers. Using inhibitors of intracellular
      signaling kinases, we found that these biological effects required activation of
      the phosphatidyl inositol-3-kinase pathway. Since sPEG-containing fibers also
      showed low levels of nonspecific protein adsorption, which is desirable in the
      context of artificial implant design, the peptide modification of fibers appears
      to provide good substrates for nerve repair.

PMID- 20818999
TI  - Elastomeric osteoconductive synthetic scaffolds with acquired osteoinductivity
      expedite the repair of critical femoral defects in rats.
AB  - Regenerative medicine aspires to reduce reliance on or overcome limitations
      associated with donor tissue-mediated repair. Structural bone allografts are
      commonly used in orthopedic surgery, with a high percentage of graft failure due
      to poor tissue integration. This problem is aggravated among elderly, those
      suffering from metabolic conditions, or those undergoing cancer therapies that
      compromise graft healing. Toward this end, we developed a synthetic graft named
      FlexBone, in which nanocrystalline hydroxyapatite (50 wt%) was structurally
      integrated with crosslinked poly(hydroxyethyl methacrylate) hydrogel, which
      provides dimensional stability and elasticity. It recapitulates the essential
      role of nanocrystalline hydroxyapatite in defining the osteoconductivity and
      biochemical microenvironment of bone because of its affinity for biomolecules.
      Here, we demonstrate that FlexBone effectively absorbed endogenously secreted
      signaling molecules associated with the inflammation/graft healing cascade upon
      being press-fit into a 5-mm rat femoral segmental defect. Further, when
      preabsorbed with a single dose of 400 ng recombinant human (rh) bone
      morphogenetic protein-2/7 heterodimer, it enabled the functional repair of the
      critical-sized defect by 8-12 weeks. FlexBone was stably encapsulated by the
      bridging bony callus and the FlexBone-callus interface was continuously
      remodeled. In summary, FlexBone combines the dimensional stability and
      osteoconductivity of structural bone allografts with desirable surgical
      compressibility and acquired osteoinductivity in an easy-to-fabricate and
      scalable synthetic biomaterial.

PMID- 20819002
TI  - Indapamide for out-patient treatment of hypertension: modifications in serum
      catecholamine levels.
AB  - A study was carried out to evaluate the efficacy of indapamide in the treatment
      of 20 patients with mild hypertension and to determine whether a favourable
      response to treatment was related to initial hyperadrenergic status, to changes
      in serum catecholamine levels or modified by orthostatic stress. After 4 weeks on
      placebo, patients received 2.5 mg indapamide per day for 4 weeks and, if
      diastolic pressure was controlled below 100 mmHg, this regimen was continued for
      a further 8 weeks. Those not adequately controlled with indapamide alone were
      treated additionally with nadolol (mean dose 140 mg per day) for a period of 12
      weeks. The results showed that indapamide alone produced a significant reduction
      in blood pressure both in the recumbent and upright position in 12 (60%) of the
      patients and that addition of the beta-blocker augmented the antihypertensive
      effect. No relationship was demonstrated between initial high serum catecholamine
      levels and a favourable response to indapamide. Recumbent serum norepinephrine
      levels after indapamide alone or with nadolol for 4 to 8 weeks remained
      comparable with placebo levels. However; the amplitude of the norepinephrine
      increase due to orthostatic stress was significantly reduced after 8 weeks of
      indapamide treatment. Possible explanations for this are discussed.

PMID- 20819005
TI  - Will deep-brain stimulation be as successful in major depression as it has been
      in Parkinson's disease?

PMID- 20819006
TI  - Impulsivity: current and future trends in pharmacological treatment.

PMID- 20819008
TI  - Vitamin D and multiple sclerosis: what are the guidelines for a reliable clinical
      trial?
AB  - Evaluation of: Mowry EM, Krupp LB, Milazzo M et al. Vitamin D status is
      associated with relapse rate in pediatric-onset multiple sclerosis. Ann. Neurol.
      67, 618-624 (2010). In 1960, Sir Donald Acheson suggested a link between multiple
      sclerosis and solar radiation. Some 50 years and numerous studies later, there is
      still no certainty about the role of UV or vitamin D, the sun-induced hormone, on
      the course of multiple sclerosis. In order to further clarify this issue, the
      article by Mowry et al. assesses the level of vitamin D in patients at the time
      of multiple sclerosis onset and correlates it with the number of subsequent
      clinical relapses. The conclusion is that every 10 ng/ml increase in the adjusted
      vitamin D level is associated with a 34% decrease in the rate of relapse. This
      result reinforces the rationale for a randomized double-blind placebo-controlled
      clinical trial. Several criteria for a well-designed trial are proposed.

PMID- 20819009
TI  - Contribution of genetic, epigenetic and transcriptomic differences to twin
      discordance in multiple sclerosis.
AB  - Evaluation of: Baranzini SE, Mudge J, van Velkinburgh JC et al. Genome, epigenome
      and RNA sequences of monozygotic twins discordant for multiple sclerosis. Nature
      464, 1351-1356 (2010). Multiple sclerosis (MS) is a chronic inflammatory disease
      of the CNS. Genetically identical (monozygotic) twins have a concordance rate for
      MS of approximately 30%, lending support to the notion that the disease has a
      complex etiology, developing as a result of genetic and environmental factors and
      their interactions. However, recent studies have highlighted the fact that
      monozygotic twins might not actually be genetically identical. In an effort to
      see if this can explain MS twin discordance, Baranzini and colleagues sequenced
      the genome from a pair of monozygotic twins discordant for MS, and also examined
      DNA methylation and gene expression across the genome in this twin pair and an
      additional two more twin pairs. No consistent differences in DNA sequence, DNA
      methylation or gene expression were found. Here we put these findings into
      context and discuss their significance.

PMID- 20819010
TI  - Cognitive-behavioral therapy: what benefits can it offer people with multiple
      sclerosis?
AB  - Cognitive-behavioral therapy (CBT) originated as a treatment for emotional
      disorders. However, it is increasingly used to help people with chronic illnesses
      manage symptoms and improve psychosocial outcomes, such as depression and quality
      of life. In this article, we focus on uses of CBT in patients with multiple
      sclerosis, an incurable neurological disease that causes potentially debilitating
      symptoms and poses numerous challenges to psychological well-being. We examine
      the rationale for using CBT to deal with distress, symptoms, impairment and
      disease exacerbation and progression, and discuss examples of existing research
      on the efficacy and acceptability of these interventions. Finally, we consider
      areas where CBT could potentially benefit people with multiple sclerosis in the
      future. Ongoing challenges in this field are discussed.

PMID- 20819011
TI  - Influence of trigger factors on the efficacy of almotriptan as early intervention
      for the treatment of acute migraine in a primary care setting: the START study.
AB  - In a large observational general practice study (the Standardized Study with
      Almotriptan in Early Treatment of Migraine [START]), 12.5 mg almotriptan
      administered within 1 h of pain onset and when pain was mild significantly
      improved pain-related outcomes, compared with later treatment or when pain was
      more severe. Migraine triggers at baseline and during treatment were recorded,
      and it was examined whether trigger factors could affect almotriptan-induced
      headache improvement. More than 400 patients were enrolled, and 1174 attacks were
      assessed. At baseline, patients reported a mean of 2.6 types of triggers related
      to the start of their previous migraine attacks. During the trial, a mean of 1.5
      trigger factors for each attack was recorded. The most frequent trigger during
      the study was stress (37% of migraine attacks), with poor sleep (34%), fatigue
      (32%) and menses (19%) also being widely reported. Stress and fatigue and/or poor
      sleep were the most frequent trigger combinations. Early treatment with
      almotriptan improved clinical outcomes, regardless of the trigger factors
      involved. Similar results were observed for nonearly administration, although
      this was less efficacious than early intervention. An exception in the nonearly
      group was that migraines triggered by poor sleep had better responses than
      attacks in which sleep disorder was not a factor. Almotriptan maintained its
      efficacy irrespective of trigger factors in migraine patients treated in everyday
      clinical practice and, as shown in other studies, it was most effective in
      reducing pain-free rates when administered early, when pain was still mild.

PMID- 20819012
TI  - Patent foramen ovale closure and migraine: science and sensibility.
AB  - Migraine has been associated with patent foramen ovale (PFO), and PFO closure has
      become the most high-profile nonpharmacologic invasive therapy recommended for
      the prevention of recurrent migraine attacks, as well as for preventing further
      attacks in cryptogenic stroke. The results of Migraine Intervention with STARFlex
      Technology (MIST), a controversial but important recent randomized clinical trial
      (RCT) of PFO closure for migraine, do not support PFO closure for preventing
      migraine attacks. All patients with migraine, however, do not have a PFO, and the
      characteristic periodicity and predictability of migraine cannot be explained on
      the basis of paradoxical embolism through the PFO. Closure of the PFO or atrial
      septal defect can aggravate migraine suddenly. PFO increases in size with age,
      but migraine generally subsides with the passage of years. Serendipity does play
      a role in some medical discoveries, but in the absence of a logically defensible
      theoretical basis, chance and statistics can both become misleading. With soft
      end points, RCTs in migraine patients can generate conflicting and irreconcilable
      data. RCTs cannot supplant or substitute clinical common sense or justify
      serendipity. Scientific progress mandates that any serendipitous research must
      ultimately conform to the principles of the basic sciences surrounding the chance
      discovery. PFO closure for preventing migraine attacks is an unfortunate, but
      sobering, chapter in the migraine research saga.

PMID- 20819013
TI  - Immunomodulatory drug treatment in multiple sclerosis.
AB  - The fundamental role of inflammatory immune processes in the pathology of
      multiple sclerosis (MS) provides the rationale for immunomodulatory therapies
      that attempt to shift the immune system from pro-inflammatory to anti
      inflammatory pathways and induce regulatory mechanisms. Growing understanding of
      immune cellular and molecular mechanisms together with modern biotechnology
      engendered promising immunomodulatory treatment strategies, with novel mechanisms
      of actions and different levels of specificity. These include inhibitory
      molecules, monoclonal antibodies, cell therapies and agents that are administered
      orally or by infrequent infusions. Several of these treatments have demonstrated
      impressive efficacy in Phase II and III clinical trials by reducing disease
      activity and accumulation of disability. However, with the advent of potent
      therapies, rare but severe adverse effects, such as CNS infections and
      malignancies, have occurred. This article describes current and upcoming
      immunomodulatory strategies for MS therapy. The potential of immunomodulatory
      treatments to counteract the inflammatory characteristics of MS and support
      neuroprotective processes is discussed.

PMID- 20819014
TI  - Multiple sclerosis-associated fatigue.
AB  - Fatigue is an extremely prevalent issue for multiple sclerosis (MS) patients.
      Fatigue can affect quality of life, depression, anxiety, motor function and sleep
      patterns. There are a number of available rating scales designed to detect and
      assess fatigue. However, the pathophysiology of fatigue is still not completely
      understood and the treatment of this symptom remains difficult. A number of
      clinical trials for fatigue in MS have shown some benefit with different
      interventions, including medication, physical activity and cognitive-behavioral
      therapy. Nonetheless, further research and the development of more targeted
      therapies are needed to improve the management of fatigue.

PMID- 20819015
TI  - Myelin lesions associated with lysosomal and peroxisomal disorders.
AB  - Abnormalities of myelin are common in lysosomal and peroxisomal disorders. Most
      display a primary loss of myelin in which the myelin sheath and/or
      oligodendrocytes are selectively targeted by diverse pathogenetic processes. The
      most severe and, hence, clinically relevant are heritable diseases predominantly
      of infants and children, the leukodystrophies: metachromatic, globoid cell
      (Krabbe disease) and adreno-leukodystrophy. Our still limited understanding of
      these diseases has derived from multiple sources: originally, neurological
      neuropathologic-neurochemical correlative studies of the natural disease in
      humans or other mammals, which has been enhanced by more sophisticated and
      contemporary techniques of cell and molecular biology. Transgenic mouse models
      seem to be the most promising methodology, allowing the examination of the
      cellular role of lysosomes and peroxisomes for formation and maintenance of both
      myelin and axons, and providing initial platforms to evaluate therapies.
      Treatment options are woefully inadequate and in their nascent stages, but still
      inspire some hope for the future.

PMID- 20819016
TI  - Neuro-ophthalmology and its contribution to headaches: a case-based approach.
AB  - Many neuro-ophthalmic conditions are associated with head or ocular pain; some
      are benign and others are potentially life-threatening. Rather than listing and
      describing numerous conditions, this article presents three cases interfacing
      neuro-ophthalmology and headache, with a discussion of the differential
      diagnosis, approach to obtaining the proper diagnosis, and management. The
      discussions are not intended to be exhaustive, but include conditions encountered
      in practice that present a diagnostic challenge. The main issues are highlighted
      for each clinical scenario.

PMID- 20819017
TI  - Management of chronic daily headache in children.
AB  - Children and adolescents can develop frequent, at times daily, headaches. The
      more severe forms of headaches that these children experience are often
      migrainous. This article discusses the typical characteristics of these patients
      and reviews treatments considered in this condition. Unfortunately, there are no
      high-quality studies to definitively guide treatment in children with chronic
      daily headache. Treatment decisions are often made using data from adult studies,
      childhood studies on episodic migraine or expert opinion. Current data on which
      to base treatment decisions are reviewed in this article.

PMID- 20819019
TI  - TRAIL receptor signaling and therapeutics.
AB  - IMPORTANCE OF THE FIELD: TNF-related apoptosis-inducing ligand (TRAIL) is a
      member of the TNF family of cytokines, which can induce apoptotic cell death in a
      variety of tumor cells by engaging specific death receptors, TRAIL-R1 and TRAIL
      R2, while having low toxicity towards normal cells. There is interest in cancer
      therapy inducing cell death by activation of the death-receptor-mediated
      apoptotic pathway while avoiding decoy-receptor-mediated neutralization of the
      signal. This has led to the development of a number of receptor-specific TRAIL
      variants and agonistic antibodies. Some of these soluble recombinant TRAIL and
      agonist antibodies targeting TRAIL-R1 and/or TRAIL-R2 are progressing in clinical
      trials. In addition, TRAIL-resistant tumors can be sensitized to TRAIL by a
      combination of TRAIL or agonistic antibodies with chemotherapeutic agents,
      targeted small molecules or irradiation. AREAS COVERED IN THIS REVIEW: Recent
      advances in developing TRAIL or its agonist receptor antibodies in cancer
      therapy. We also discuss combination therapies in overcoming TRAIL resistance in
      cancer cells. WHAT THE READER WILL GAIN: Knowledge of current clinical trials,
      the promise and obstacles in the future development of therapies affecting TRAIL
      signaling pathways. TAKE HOME MESSAGE: Cancer therapeutics targeting the
      TRAIL/TRAIL receptor signaling pathway hold great promise for molecularly
      targeted pro-apoptotic anti-cancer therapy.

PMID- 20819020
TI  - Wound healing properties of Indian propolis studied on excision wound-induced
      rats.
AB  - CONTEXT: In traditional medicine propolis is widely used for the treatment of
      various ailments including ulcer and wound healing. The phytochemical screening
      of Indian propolis indicates the presence of biologically active ingredients in
      appreciable amounts. In the absence of systematic evaluation of wound healing
      properties of Indian propolis in the literature, the present study was
      undertaken. OBJECTIVE: The aim of this study was to evaluate the wound healing
      potential of Indian propolis on excision wounds induced in experimental rats.
      MATERIALS AND METHODS: Excision wounds were created in male Wistar rats and were
      treated with Indian propolis ointment (nitrofurazone was used as a reference drug
      - widely used for wound healing) for a period of 14 days. Control rats were
      treated with petroleum jelly. The parameters analyzed include wound contraction,
      hydroxyproline, hexosamine, uronic acid, total protein, DNA, and RNA. RESULTS:
      Topical application of propolis ointment for 14 days significantly improved the
      wound contraction when compared to the control group of rats. The determination
      of hydroxyproline, hexosamine, uronic acid, DNA, RNA and protein levels in the
      wound matrix revealed the pro-healing effects of propolis. The results obtained
      were comparable with nitrofurazone. DISCUSSION AND CONCLUSION: It appears that
      the ethanol extract of Indian propolis possesses significant pro-healing activity
      by accelerating the healing process at various phases of tissue repair. The
      presence of biologically active ingredients such as flavonoids, phenolic acids,
      terpenes, benzoic acids, amino acids and vitamins, etc. in Indian propolis may
      readily account for the observed prophylactic action of propolis in wound
      healing.

PMID- 20819021
TI  - Optimization of podophyllotoxin extraction method from Linum album cell cultures.
AB  - CONTEXT: Suspension cultures of Linum album Kotschy ex Boiss. (Linaceae)
      accumulate podophyllotoxin (an anticancer agent) and could therefore serve as an
      alternative source of this important aryltetralin lactone lignan. OBJECTIVE: The
      present work compared four podophyllotoxin extraction methods and optimization of
      the best one by using single factor experiments. MATERIALS AND METHODS: Linum
      album cell cultures were established from in vitro plantlets and subcultured in
      MS medium with hormones every 7-8 days. Four podophyllotoxin extraction methods
      were assayed and the best one was optimized by single factor experiments,
      studying the effect of methanol concentration, extraction time, and sonication
      time. RESULTS: Cell cultures accumulated enough podophyllotoxin to be analyzed by
      HPLC. The methanol/dichloromethane and buffer extraction methods were found to be
      the best. Methanol alone and hot ethanol were not effective for extracting
      podophyllotoxin. DISCUSSION AND CONCLUSION: The optimized method based on
      methanol/dichloromethane extraction combined with HPLC quantification was able to
      determine small amounts of podophyllotoxin in Linum album cell cultures, showing
      that this system could constitute a possible alternative source of
      podophyllotoxin to Podophyllum (Berberidaceae).

PMID- 20819022
TI  - Antinociceptive effect of methanol extract of Capparis ovata in mice.
AB  - CONTEXT: Capparis ovata Desf. (Capparaceae) grows widely in Turkey. Flower buds
      and fruits of the plant are used in folk medicine for their analgesic,
      antirheumatismal, and diuretic effects. OBJECTIVE: This study evaluated the
      possible antinociceptive effect of the methanol extract of C. ovata (CME) in
      mice. MATERIALS: The antinociceptive effect of methanol extract, prepared with
      the C. ovata flower buds, was studied at the doses of 50, 100, and 200 mg/kg
      (i.p.) using tail-immersion, hot-plate, and writhing tests in mice. Morphine
      sulfate (5 mg/kg; i.p.) and dipyrone (100 mg/kg; i.p.) were used as reference
      analgesic agents. Naloxone (5 mg/kg; i.p.) was also tested. RESULTS: It was
      observed that the C. ovata extract had a significant antinociceptive effect in
      these tests. In the hot-plate and tail-immersion test results, the doses of 50,
      100, and 200 mg/kg increased the percentage of the maximum possible effect (MPE%)
      value for nociception significantly according to the control value (P < 0.001).
      All doses of the extract decreased the number of acetic acid-induced abdominal
      constrictions in mice when compared with control group (P < 0.001). These effects
      were inhibited by pretreatment with naloxone. DISCUSSION AND CONCLUSION: Based on
      the results obtained, it can be concluded that CME is a potentially
      antinociceptive agent which acts as both at the peripheral and central levels.

PMID- 20819023
TI  - In vitro antiviral activity from Acanthospermum australe on herpesvirus and
      poliovirus.
AB  - CONTEXT: The Asteraceae family has been of interest to researchers due to the
      presence of polyphenolic compounds, mainly flavonoids, which demonstrated
      antiviral activity. OBJECTIVE: The hydroethanol extract of the aerial parts of
      Acanthospermum australe (Loefl.) Kuntze (Asteraceae) and its fractions, were
      evaluated in vitro for their potential cytotoxic and antiviral activity against
      bovine herpesvirus and human poliovirus. MATERIALS AND METHODS: The
      sulforhodamine B colorimetric assay were used to evaluate the capacity of the
      hydroethanol extract and fractions to inhibit the lytic activity of herpes and
      poliovirus in infected cell cultures and their influence on the viability of
      uninfected cell cultures. RESULTS AND DISCUSSION: A progressive increase in the
      antiviral effect against herpesvirus was observed in the course of the
      purification process of the extract. The hydroethanol extract had a 50% antiviral
      effective concentration (EC(50)) at 70 MUg/mL and 36 MUg/mL for herpes and
      poliovirus, respectively, and it exhibited no cytotoxicity. The fractions F3
      (dichloromethane) and F4 (dichloromethane: ethyl acetate (1:1 v/v)) both showed
      EC(50) at 6.25 MUg/mL against herpesvirus, and these fractions showed cytotoxic
      concentrations (CC(50)) at 12.7 and 11.7 MUg/mL, respectively. These fractions
      had no effect against poliovirus in the concentrations tested. From the bioactive
      F3, a diterpene lactone (acanthoaustralide-1-O-acetate) was isolated at a
      concentration of 0.5% and from F4 two flavonoids (quercetin and chrysosplenol D)
      were isolated at concentrations of 0.14 and 0.24%, respectively. CONCLUSION: The
      present study reports for the first time the antiviral activity of extracts and
      fractions from A. australe aerial parts.

PMID- 20819024
TI  - Comparative study of the effect of a daily steroid regimen versus a weekly oral
      pulse steroid regimen on morphological changes, blood sugar, bone mineral density
      and suprarenal gland activity.
AB  - BACKGROUND: The most serious side effects of systemic steroids include
      osteoporosis and suprarenal suppression. Many steroid regimens have been
      suggested to minimize these side effects; one of them is oral steroid pulse
      therapy. OBJECTIVE: To compare the side effects of a daily oral steroid regimen
      versus a weekly oral steroid pulse regimen on bone mineral density and suprarenal
      suppression. METHODS: Thirty patients with different skin diseases were divided
      into two groups: 15 for oral daily steroids (ODS) (group 1) and 15 for weekly
      oral pulse steroids (WOPS) (group 2). They were evaluated for bone mineral
      density (measured by DEXA) and suprarenal suppression (measured by serum cortisol
      level), morphological changes and blood sugar. Treatment was continued for 6
      months to 3 years. RESULTS: Cushingoid features in group 1 were observed in 73%,
      yet they were not detectable in group 2. Disturbed blood sugar in group 1 was 33%
      and 0% in group 2. The serum cortisol level was lower in patients on ODS than
      those on WOPS. The effect of WOPS on bone mineral density was very limited in
      comparison with the ODS. CONCLUSION: Weekly oral steroid pulse therapy induces no
      significant bone loss and no suprarenal suppression and can be an alternative
      option in the treatment of chronic disorders requiring long-term oral steroid
      therapy.

PMID- 20819025
TI  - Antimycoplasmal activity of some plant species from northern Nigeria compared to
      the currently used therapeutic agent.
AB  - CONTEXT: Mycoplasma spp. are obligate parasites of humans and animals. But due to
      the special requirements needed to culture Mycoplasma in the laboratory, little
      or no research has been done to evaluate the efficacy of medicinal plants on the
      organism. OBJECTIVE: To screen medicinal plants traditionally used to treat
      infections for possible antimycoplasmal and cytotoxic activities. MATERIALS AND
      METHODS: Acetone extracts of 21 Nigerian medicinal plants were analyzed for
      antimycoplasmal and cytotoxicity activities using the metabolic inhibition and
      colorimetric methods, respectively. The extract with the best antimycoplasmal
      activities was also analyzed for its phytochemical constituents using the desktop
      method. RESULTS: Calotropis procera (Aiton) R.Br (Asclepiadaceae) extract had the
      best antimycoplasmal effect with a minimum inhibitory concentration (MIC) of 80
      ug/mL and minimum mycoplasmacidal concentration (MMC) of 160 ug/mL. This extract
      contained saponins, tannins, cardiac glycosides, alkaloids, and flavonoids. The
      extract of Vernonia amygdalina Delile (Compositae) was the most cytotoxic with
      median lethal concentration (LC(50)) of approximately 17 ug/mL, and that of
      Anacardium occidentale L. (Anacardiaceae) was the least cytotoxic with an LC(50)
      of approximately 1919 ug/mL. DISCUSSION: Calotropis procera is a promising plant
      for an alternative antimycoplasmal agent because the crude acetone extract had a
      higher mycoplasmacidal activity than the conventional drug tylosin, which is
      currently used in treatment of the disease in Nigeria. CONCLUSION: The crude
      extract of Calotropis procera is worth investigating for the development of a
      potent agent against cattle Mycoplasma, which has long defied solution by
      conventional chemotherapy.

PMID- 20819026
TI  - Bilateral vibrant soundbridge implantation: audiologic and subjective benefits in
      quiet and noisy environments.
AB  - CONCLUSIONS: The results support bilateral sequential implantation for patients
      who are not completely satisfied after implantation of one side. OBJECTIVE: To
      evaluate the benefit of bilateral Vibrant Soundbridge middle ear implantation as
      compared with unilateral implantation in quiet and noisy environments. METHODS:
      This was a multicentric and retrospective study of 15 patients with symmetrical
      sensorineural hearing loss who were implanted sequentially in both ears. The
      performance of each subject was compared under three conditions: with the right
      implant activated, with the left implant activated, and with both implants
      activated. Audiometric tests were compared with self-assessment subjective
      evaluation by questionnaire. RESULTS: Both qualitative and quantitative
      assessments demonstrated improvement in speech intelligibility, especially in
      background noise, but also for low voice intensity in quiet.

PMID- 20819036
TI  - No cancer health without mental health.

PMID- 20819037
TI  - Hospital capacity: what is the measure and what is the goal?

PMID- 20819038
TI  - Mandatory performance reporting as part of health care reform: but where are the
      clinical data?

PMID- 20819039
TI  - Influenza vaccination of the egg-allergic individual.

PMID- 20819040
TI  - Australia's health 2010: an overview of infectious diseases.

PMID- 20819041
TI  - Late mortality and second cancers in an Australian cohort of childhood cancer
      survivors.
AB  - OBJECTIVE: The aim of this study was to characterise rates of late mortality and
      second cancers in an Australian cohort of childhood cancer survivors and compare
      these to rates observed in the New South Wales population. DESIGN, SETTING AND
      PARTICIPANTS: Records for 896 childhood cancer survivors treated at the Sydney
      Children's Hospital between 1972 and 1999 were linked to the National Death Index
      and NSW Central Cancer Registry to identify deaths and notifications of second
      cancers. Survivors were defined as those alive for at least 5 years after
      diagnosis and were followed until death or 31 December 2004, whichever occurred
      first. MAIN OUTCOME MEASURES: Standardised mortality ratios (SMRs) and
      standardised incidence ratios (SIRs) were used as measures of relative risk. A
      Cox proportional hazard model was used to quantify the influence of demographic
      and disease-related characteristics on the risk of death and second cancers.
      RESULTS: The SMR and SIR were 7.46 and 4.98 times higher, respectively, among
      cancer survivors relative to the NSW population. Relative mortality was highest
      in survivors of soft-tissue sarcoma (SMR, 18.95 [95% CI, 6.88-40.81]) and central
      nervous system (CNS) malignancies (SMR, 16.78 [95% CI, 7.62-31.64]). The leading
      causes of death included recurrence of the primary childhood cancer (55%) and
      second cancers (12%), as well as treatment-related complications (17%) The most
      frequently observed second cancers were bone and thyroid cancers, melanoma, and
      CNS malignancies, and second cancers were most common among survivors of
      leukaemia, soft-tissue sarcoma and Hodgkin's lymphoma. CONCLUSIONS: Compared with
      the general population, survivors of childhood cancer in Australia are at
      increased risk of late mortality and second cancers. These findings highlight a
      continuing need to assess health issues faced by childhood cancer survivors and
      develop strategies to minimise the adverse outcomes associated with treatment for
      childhood cancer.

PMID- 20819042
TI  - International medical students and migration: the missing dimension in Australian
      workforce planning?
AB  - OBJECTIVE: To investigate the potential contribution of international medical
      students at Australian universities to the Australian medical workforce. DESIGN,
      SETTING AND PARTICIPANTS: A prospective survey in 2006-2007 of 619 international
      medical students in their final 2 years of undergraduate- and graduate-entry
      medical courses across eight Australian universities, followed by a 2009 survey
      of 88 international medical graduates of the University of Melbourne (most of
      whom were respondents of the earlier survey), assessing the correlation between
      students' intended place of internship and their actual place of internship. MAIN
      OUTCOME MEASURES: The survey respondents' preferred internship location; the
      proportion of respondents who intended to remain in practice in Australia long
      term; and correlation between respondents' intended internship locations and
      actual placements in their first postgraduate year. RESULTS: Of the 619
      international medical students surveyed in 2006, 358 (58%) responded. Most
      planned to undertake Australian internships and seek permanent-resident status,
      although a third were undecided about their long-term plans. Nationality was a
      highly significant variable. Most preferred city rather than regional or rural
      training locations and expressed interest in migrating to Australia. The 2009
      survey of the University of Melbourne's 2008 medical graduates showed a high
      correlation between students' plans in their last two years of study and outcomes
      in their first postgraduate year, with 73% accepting Victorian internships for
      2009. CONCLUSION: International medical students studying at Australian
      universities represent a substantial and highly acceptable medical workforce
      resource for Australia. Their requirement for internships needs to be considered
      in, and should influence, infrastructure planning.

PMID- 20819043
TI  - Brain abnormalities detected on magnetic resonance imaging of amphetamine users
      presenting to an emergency department: a pilot study.
AB  - OBJECTIVES: To determine the prevalence of occult brain abnormalities in magnetic
      resonance imaging of active amphetamine users. DESIGN, SETTING AND PARTICIPANTS:
      Prospective convenience study in a tertiary hospital emergency department (ED).
      Patients presenting to the ED for an amphetamine-related reason were eligible for
      inclusion. We collected demographic data, drug use data, and performed a mini
      mental state examination (MMSE). MAIN OUTCOME MEASURES: The proportion of
      patients with an abnormality on their MRI scan. RESULTS: Of 38 patients enrolled,
      30 had MRI scans. Nineteen were male and their mean age was 26.7 +/- 5.4 years
      (range 19-41 years). The mean age of first amphetamine use was 18 years (range 13
      26 years). Sixteen patients used crystal methamphetamine (mean amount 2.5
      g/week), nine used amphetamine ("speed") (mean amount 2.9 g/week), and 23 used
      ecstasy (mean amount 2.3 tablets/week). Marijuana was smoked by 26 (mean amount
      5.9 g/week), and 28 drank alcohol (mean amount 207 g/week). The median MMSE score
      was 27/30 (interquartile range, 26-29). Abnormalities on brain MRI scans were
      identified in six patients, most commonly an unidentified bright object (n = 4).
      CONCLUSION: In this pilot study of brain MRI of young people attending the ED
      with an amphetamine-related presentation, one in five had an occult brain lesion.
      While the significance of this is uncertain, it is congruent with evidence that
      amphetamines cause brain injury.

PMID- 20819044
TI  - How much is too much? Alcohol consumption and related harm in the Northern
      Territory.
AB  - OBJECTIVE: To present recent estimates of alcohol consumption and its impact on
      the health of people in the Northern Territory, and to draw comparisons with
      Australia as a whole. DESIGN, SETTING AND PARTICIPANTS: Descriptive study of
      alcohol consumption in the NT population, based on sales data and self-report
      surveys, and alcohol-attributable deaths and hospitalisations among people in the
      NT in the 2004-05 and 2005-06 financial years using population alcohol
      attributable fractions specific to the NT. MAIN OUTCOME MEASURES: Per capita
      consumption of pure alcohol, self-reported level of consumption, and age
      standardised rates of death and hospitalisation attributable to alcohol. RESULTS:
      Apparent per capita consumption of pure alcohol for both Aboriginal and non
      Aboriginal populations in the NT has been about 14 litres or more per year for
      many years, about 50% higher than for Australia as a whole. We estimated that
      there were 120 and 119 alcohol-attributable deaths in the NT in 2004-05 and 2005
      06, respectively, at corresponding age-standardised rates of 7.2 and 7.8 per 10
      000 adult population. Alcohol-attributable deaths occur in the NT at about 3.5
      times the rate they do in Australia generally; rates in non-Aboriginal people
      were about double the national rate, while they were 9-10 times higher in
      Aboriginal people. There were 2319 and 2544 alcohol-attributable hospitalisations
      in the NT in 2004-05 and 2005-06, respectively, at corresponding rates of 146.6
      and 157.7 per 10 000 population (more than twice the national rate). CONCLUSION:
      In recent years, alcohol consumption and consequent alcohol-attributable deaths
      and hospitalisations for both Aboriginal and non-Aboriginal people in the NT have
      occurred at levels far higher than elsewhere in Australia.

PMID- 20819045
TI  - Legal aspects of open disclosure: a review of Australian law.
AB  - Health professionals worry that information about adverse events conveyed to
      patients in open disclosure (OD) may be used against them in medicolegal
      proceedings. Whether and how strongly state and federal laws in Australia protect
      against such uses is unclear. Our analysis concludes that existing laws do not
      prohibit the sharing of most types of information on adverse events with
      patients. However, none of these laws was enacted with OD in mind and, in
      general, the protections they provide are quite weak. If policymakers want OD to
      become a routine part of medical practice, law reform may be needed in the form
      of stronger protections directed specifically at the contents of OD
      communications.

PMID- 20819046
TI  - Perceptions of preparation for further training: how our medical schools prepare
      graduates and the perceived factors influencing access to training.
AB  - OBJECTIVE: To investigate the specific factors that graduates perceive to
      influence their success in obtaining primary training in a chosen field. DESIGN,
      SETTING AND PARTICIPANTS: The New South Wales Medical Registration Board provided
      data on doctors who were registered to practise between 1995 and 2006. A brief,
      paper-based survey was sent to a random selection of 2000 doctors. MAIN OUTCOME
      MEASURES: Doctors' self-reported perceptions on the impact of demographic
      details, specialty training applied for, university training and other factors on
      opportunities for further training after medical school. RESULTS: Of the 375/1915
      doctors (19.6%) who responded, most had completed a 6-year undergraduate degree
      from the University of Sydney, University of NSW or University of Newcastle, and
      most were at registrar level. Of 242/321 doctors (76%) who had applied for a
      training position, 240 (99%) had been accepted. The support of a mentor was
      considered the most positive influence on meeting long-term career goals (255/318
      [80%]). Learning how to communicate with patients was valued as the most helpful
      aspect of medical school (270/318 [85%]). CONCLUSION: The personal attributes of
      graduates were considered more influential in achieving career goals and
      accessing further training than perceived features of a medical program. This
      suggests that more emphasis and research should be devoted to selecting the most
      appropriate candidates, rather than restructuring medical curricula to meet a
      presumed need for more content knowledge before graduation.

PMID- 20819047
TI  - Outcomes of appendicectomy in an acute care surgery model.
AB  - OBJECTIVE: To assess the outcomes of appendicectomy in an acute care surgery
      (ACS) model compared with a traditional on-call (Trad) model. DESIGN:
      Retrospective historical control study comparing appendicectomy outcomes in the
      Trad period (April 2004 to March 2005) with outcomes in the ACS period (April
      2006 to March 2007). SETTING: The Prince of Wales Public Hospital, a metropolitan
      tertiary referral centre in Sydney. PATIENTS: All adult patients undergoing
      appendicectomy during 1-year periods before and after the introduction of the ACS
      model. INTERVENTION: The introduction of an ACS model for managing all emergency
      general surgical presentations. MAIN OUTCOME MEASURE: Complication rate. RESULTS:
      A total of 402 appendicectomies were performed, 176 during the Trad period and
      226 during the ACS period. There was no perioperative mortality. The complication
      rate was lower in the ACS period than the Trad period (9.3% v 17.0%; P = 0.02).
      After the intervention, there was no significant change in the time from
      presentation to arrival in theatre or in length of stay, but the proportion of
      operations performed at night (24:00-08:00) was reduced from 26.1% to 15.0% (P =
      0.006). The proportion of negative appendicectomies was reduced from 22.7% to
      17.3%, but the change was not statistically significant (P = 0.08). There was no
      difference in perforation rate before and after the intervention (13.6% v 13.3%;
      P = 0.86). CONCLUSION: The ACS model provides a safe surgical environment for
      patients and is associated with a reduced complication rate. Under the ACS model,
      there was an increase in the number of patients treated conservatively overnight,
      but this did not lead to an overall increase in perforation rate or length of
      stay.

PMID- 20819048
TI  - Changes in serial laboratory test results in snakebite patients: when can we
      safely exclude envenoming?
AB  - OBJECTIVES: To determine which laboratory tests are first associated with severe
      envenoming after a snakebite, when (ie, how long after the bite) the test results
      become abnormal, and whether this can determine a safe observation period after
      suspected snakebite. DESIGN, PATIENTS AND SETTING: Prospective cohort study of
      478 patients with suspected or confirmed snakebite recruited to the Australian
      Snakebite Project from January 2002 to April 2009, who had at least three sets of
      laboratory test results and at least 12 hours of observation in hospital after
      the bite. Severe envenoming was defined as venom-induced consumption coagulopathy
      (VICC), myotoxicity, neurotoxicity or thrombotic microangiopathy. MAIN OUTCOME
      MEASURES: International normalised ratio (INR), activated partial thromboplastin
      time (aPTT), creatine kinase (CK) level, and neurological examination. RESULTS:
      There were 240 patients with severe envenoming, 75 with minor envenoming and 163
      non-envenomed patients. Of 206 patients with VICC, 178 had an INR > 1.2
      (abnormal) on admission, and the remaining 28 had an INR > 1.2 within 12 hours of
      the bite. Of 33 patients with myotoxicity, a combination of CK > 250 U/L and an
      abnormal aPTT identified all but two cases by 12 hours; one of these two was
      identified within 12 hours by leukocytosis. Nine cases of isolated neurotoxicity
      had a median time of onset after the bite of 4 hours (range, 35 min - 12 h). The
      combination of serial INR, aPTT and CK tests and repeated neurological
      examination identified 213 of 222 severe envenoming cases (96%) by 6 hours and
      238 of 240 (99%) by 12 hours. CONCLUSION: Laboratory parameters (INR, aPTT and
      CK) and neurological reassessments identified nearly all severe envenoming cases
      within 12 hours of the bite, even in this conservative analysis that assumed
      normal test results if the test was not done.

PMID- 20819049
TI  - Hospital bed occupancy: more than queuing for a bed.
AB  - Timely access to safe hospital care remains a major concern. Target bed-occupancy
      rates have been proposed as a measure of the ability of a hospital to function
      safely and effectively. High bed-occupancy rates have been shown to be associated
      with greater risks of hospital-associated infection and access block and to have
      a negative impact on staff health. Clinical observational data have suggested
      that bed occupancies above 85% could adversely affect safe, effective hospital
      function. Using this figure, at least initially, would be of value in the
      planning and operational management of public hospital beds in Australia. There
      is an urgent need to develop meaningful outcome measures of patient care that
      could replace the process measures currently in use.

PMID- 20819051
TI  - Myths of ideal hospital size.
AB  - Current methods used to calculate the required size of hospitals are
      underestimating the true capacity needed for operational efficiency. Trends in
      occupied bed-days (rather than admissions and length of stay) give better
      estimates of future bed requirements. Hospital occupancy rates depend on
      volatility in demand, not efficiency. Larger bed pools and hospitals can operate
      at higher average occupancy. Cost efficiency should be focusing on staffing based
      on the patients in the beds and not on the available beds. Hospitals require
      supporting climatalogical forecasts to allow for seasonal and other climate
      related changes in admissions, if flexible staff deployment is to become a
      reality.

PMID- 20819050
TI  - Serious morbidity associated with misuse of over-the-counter codeine-ibuprofen
      analgesics: a series of 27 cases.
AB  - OBJECTIVE: To investigate morbidity related to misuse of over-the-counter (OTC)
      codeine-ibuprofen analgesics. DESIGN AND SETTING: Prospective case series
      collected from Victorian hospital-based addiction medicine specialists between
      May 2005 and December 2008. MAIN OUTCOME MEASURES: Morbidity associated with
      codeine-ibuprofen misuse. RESULTS: Twenty-seven patients with serious morbidity
      were included, mainly with gastrointestinal haemorrhage and opioid dependence.
      The patients were taking mean daily doses of 435-602 mg of codeine phosphate and
      6800-9400 mg ibuprofen. Most patients had no previous history of substance use
      disorder. The main treatment was opioid substitution treatment with buprenorphine
      naloxone or methadone. CONCLUSIONS: Although codeine can be considered a
      relatively weak opioid analgesic, it is nevertheless addictive, and the
      significant morbidity and specific patient characteristics associated with
      overuse of codeine-ibuprofen analgesics support further awareness, investigation
      and monitoring of OTC codeine-ibuprofen analgesic use.

PMID- 20819052
TI  - Hospital beds: a primer for counting and comparing.
AB  - There is considerable public, political and professional debate about the need
      for additional hospital beds in Australia. However, there is no clarity in regard
      to the definition, meaning and significance of hospital bed counts. Relative to
      population, there has been a total decline in bed availability in Australia over
      the past 15 years of 14.6% (22.9% for public hospital beds). This decline is
      partly offset by reductions in length of stay and changes to models of care;
      however, the net effect is increased bed occupancy which has in turn resulted in
      system-wide congestion. Future bed capability needs to be better planned to meet
      growing demands while at the same time continuing trends for more efficient use.
      Future planning should be based in part on weighted bed capability matched to
      need.

PMID- 20819053
TI  - Posterior scleritis mimicking orbital cellulitis.

PMID- 20819054
TI  - Iodine deficiency in Australia: is iodine supplementation for pregnant and
      lactating women warranted? Comment.

PMID- 20819055
TI  - Closing the gap - better health intelligence is required.

PMID- 20819056
TI  - Cardiovascular risk perception and evidence-practice gaps in Australian general
      practice.

PMID- 20819057
TI  - Myths of ideal hospital occupancy.

PMID- 20819058
TI  - Ask patients about their internet use.

PMID- 20819059
TI  - Combination of fenofibrate with non-statin drug regimens.
AB  - OBJECTIVE: We present the available data on the effects of combined therapy of
      fenofibrate with drugs affecting lipid metabolism other than statins. METHODS: We
      consider studies evaluating the effects of combined therapy of fenofibrate with
      bile acid sequestrants (BAS), ezetimibe, niacin, n-3 fatty acids, plant sterols,
      orlistat, rimonabant, metformin and glitazones. RESULTS: Combination of BAS
      (especially colesevelam) with fenofibrate had additional effects on metabolic
      parameters in patients with mixed hyperlipidemia. Combination of ezetimibe with
      fenofibrate may be a useful approach to improve the overall lipid profile of
      patients with mixed hyperlipidemia. There is a further reduction in triglyceride
      levels when n-3 fatty acids are administered with fenofibrate in patients with
      severe hypertriglyceridemia. Combined fenofibrate and orlistat treatment further
      improves metabolic parameters in overweight/obese patients with metabolic
      syndrome. The fenofibrate/thiazolidinedione combination is an alternative for
      diabetic patients intolerant to statins, though differences exist between
      pioglitazone and rosiglitazone. CONCLUSIONS: For patients who cannot tolerate
      statins there are useful combinations of fenofibrate with other drugs affecting
      lipid metabolism. These combinations improve several metabolic parameters, but
      more trials should be carried out to reach more robust conclusions about their
      effects on cardiovascular events.

PMID- 20819060
TI  - Carbonic anhydrases: again, and again, and again.

PMID- 20819061
TI  - Saccharomyces cerevisiae beta-carbonic anhydrase: inhibition and activation
      studies.
AB  - The beta-carbonic anhydrase from Saccharomyces cerevisiae (CA, EC 4.2.1.1), scCA,
      which is encoded by the Nce103 gene, is an effective catalyst for CO(2) hydration
      to bicarbonate and protons, with a k(cat) of 9.4 x 10(5) s(-1), and k(cat)/K(M)
      of 9.8 x 10(7) M(-1).s(-1). Its inhibition with anions and sulfonamides has been
      investigated, as well as its activation with amines and amino acids. Bromide,
      iodide and sulfamide, were the best anion inhibitors, with K(I)s of 8.7 - 10.8
      uM. Benzenesulfonamides substituted in 2-, 4- and 3,4-positions with amino,
      alkyl, halogeno and hydroxyalkyl moieties had K(I)s in the range of 0.976 - 18.45
      uM. Better inhibition (K(I)s in the range of 154 - 654 nM) was observed for
      benzenesulfonamides incorporating aminoalkyl/carboxyalkyl moieties or
      halogenosulfanilamides; benzene-1,3-disulfonamides; simple heterocyclic
      sulfonamides and sulfanilyl-sulfonamides. The clinically used
      sulfonamides/sulfamate (acetazolamide, ethoxzolamide, methazolamide, dorzolamide,
      topiramate, celecoxib, etc.) generally showed effective scCA inhibitory activity,
      with K(I)s in the range of 82.6 - 133 nM. The best inhibitor (K(I) of 15.1 nM)
      was 4-(2-amino-pyrimidin-4-yl)-benzenesulfonamide. L-adrenaline and some
      piperazines incorporating aminoethyl moieties were the most effective scCA
      activators. These studies may lead to a better understanding of the role of this
      enzyme in yeasts/fungi, and since the Nce103 gene is also present in many
      pathogenic organisms (Candida spp., Cryptococcus neoformans, etc) they may be
      useful to develop antifungal drugs.

PMID- 20819062
TI  - 3-phenyl-1H-indole-5-sulfonamides: structure-based drug design of a promising
      class of carbonic anhydrase inhibitors.
AB  - A series of 2-(hydrazinocarbonyl)-3-substituted-phenyl-1H-indole-5-sulfonamides
      possessing various 2-, 3- or 4- substituted phenyl groups with methyl-, halogeno-
      and methoxy- functionalities, as well as the perfluorophenyl moiety have been
      synthesized and evaluated as inhibitors of both alpha- and beta-class carbonic
      anhydrases (CAs, EC 4.2.1.1). All human isoforms with medicinal chemistry
      applications were included in such studies, among which CA I, II, VA, VB, VII, IX
      and XII. Several low nanomolar, sometimes isoform-selective compounds were thus
      detected. Two beta-CAs from the pathogenic bacterium Mycobacterium tuberculosis
      encoded by the genes Rv1284 Rv3588c were also highly inhibited (sometimes in the
      sub-nanomolar range) by some pyridinium derivatives incoprorating this scaffold,
      obtained from the corresponding 2-(hydrazinocarbonyl)-3-substituted-phenyl-1H
      indole-5-sulfonamides by reaction with pyrylium salts. The fungal beta-CAs from
      Candida albicans (Nce103) and Cryptococcus neoformans (Can2) were also
      investigated for their inhibition with this family of sulfonamides and some
      highly effective inhibitors detected. As the X-ray crystal structure of one such
      sulfonamide with the human isoform CA II is also know, the 3-substituted-phenyl
      1H-indole-5-sulfonamides represent a totally new class of inhibitors obtained by
      structure-based drug design, which show efficiency in inhibiting both alpha- and
      beta-CAs from several species.

PMID- 20819063
TI  - Brucella carbonic anhydrases: new targets for designing anti-infective agents.
AB  - The facultative intracellular pathogen and zoonotic agent Brucella sp. possesses
      two carbonic anhydrases (CAs, EC 4.2.1.1), termed bsCA I and bsCA II (in Brucella
      suis), belonging to the &beta;-class of these metalloproteins. These zinc
      enzymes, present in many other pathogenic bacteria, have been considered recently
      as potential antibacterial targets. The catalytic activity of bsCA II is higher
      than that of bsCA I (for the conversion of CO(2) to bicarbonate). Both enzymes
      were inhibited by the well-studied inhibitor acetazolamide, a sulfonamide drug. A
      library of 41 sulfonamides and one sulfamate, among which 12 clinically tested
      drugs, was used for inhibition studies with bsCA I and II. These compounds were
      generally much more potent inhibitors of bsCA I (K(Is) of 17-75 nM) than of
      bsCAII (K(I)s of 84-923nM). However, certain glycosidic sulfonamide derivatives
      exhibited the same strong inhibitory activity on both bsCA I and bsCA II (K(Is)
      of 8.9-20 nM). Furthermore, at least one of these glycosylsulfonamides showed a
      significant inhibition of B. suis growth after 8-11 days of culture in minimal
      medium. In conclusion, as &beta;-CAs of Brucella are susceptible to inhibition by
      a wide range of aromatic and heteroaromatic sulfonamides, they may represent
      novel targets for the development of clinically useful antibacterial agents.

PMID- 20819064
TI  - The beta-carbonic anhydrases from Mycobacterium tuberculosis as drug targets.
AB  - Three beta-carbonic anhydrases (CAs, EC 4.2.1.1), encoded by the gene Rv1284
      (mtCA 1) Rv3588c (mtCA 2) and Rv3273 (mtCA 3) are present in the human pathogen
      Mycobacterium tuberculosis. These enzymes were cloned and they showed appreciable
      catalytic activity for CO(2) hydration, with k(cat) of 3.9 x 10(5) s(-1), and
      k(cat)/K(m) of 3.7 x 10(7) M(-1).s1 for mtCA 1, of 9.8 x 10(5) s(-1), and
      k(cat)/K(m) of 9.3 x 10(7) M(-1).s(-1) for mtCA 2 and k(cat) of 4.3 x 10(5) s(
      1), and a k(cat)/K(m) of 4.0 x 10(7) M(-1).s(-1) for mtCA 3, respectively. The
      Rv3273 gene product is predicted to be a 764 amino acid residues polypeptide,
      consisting of a sulfate transporter domain (amino acids 121-414) in addition to
      the beta-CA mentioned above (which is encoded by residues 571-741). All these
      enzymes were inhibited appreciably by many sulfonamides and sulfamates, in the
      nanomolar - micromolar range, whereas some subnanomolar inhibitors were also
      reported for two of them (mtCA 1 and mtCA 3). As sulfonamides also efficiently
      inhibit dehydropteroate synthetase (DHPS), the contribution of mtCAs and DHPS
      inhibition to a possible antimycobacterial action of these drugs must be better
      understood. It has been, however, proven that mtCAs are druggable targets, with a
      real potential for developing antimycobacterial agents with a diverse mechanism
      of action compared to the clinically used drugs for which many strains exhibit
      multi-drug resistance and extensive multi-drug resistance, although for the
      moment no in vivo inhibition of the bacteria could be evidenced with the
      presently available drugs due to lack of penetrability through the mycolic acid
      cell wall of M. tuberculosis.

PMID- 20819065
TI  - Modulation of carbonic anhydrase 9 (CA9) in human brain cancer.
AB  - Hypoxia is a crucial factor in tumour aggressiveness and its treatment
      resistance, particularly in human brain cancer. Tumour resistance against
      radiation- and chemo- therapy is facilitated by oxygenation reduction at tumour
      areas. HIF-1alpha regulated genes are mostly responsible for this type of
      resistance. Among these genes, carbonic anhydrase isoform 9 (CA9) is highly
      overexpressed in many types of cancer especially in high grade brain cancer like
      GBM. CA IX contributes to tumour environment acidification by catalyzing the
      carbon dioxide hydration to bicarbonate and protons, leading to the acquisition
      of metastasic phenotypes and chemoresistance to weakly basic anticancer drugs and
      therefore to inadequate application of radio-therapeutic or chemotherapeutic anti
      cancer treatment strategies. Inhibition of this enzymatic activity by application
      of specific chemical CA9 inhibitors (sulphonamide derivative compounds) or
      indirect inhibitors like HIF-1alpha inhibitors (chetomin) or molecular inhibitors
      like CA9-siRNA leads to reversion of these processes, leading to the CA9
      functional role inhibition during tumourigenesis. Hypoxia significantly
      influences the tumour microenvironment behaviour via activation of genes involved
      in the adaptation to the hypoxic stress. It also represents an important cancer
      prognosis indicator and is associated with aggressive growth, malignant
      progression, metastasis and poor treatment response. The main objective in
      malignant GBM therapy is either to eradicate the tumour or to convert it into a
      controlled, quiescent chronic disease. Sulfonamide derivative compounds with CA9
      inhibitory characteristics represent one of the optimal treatment options beside
      other CA9 inhibitory agents or chemical inhibitory compounds against its main
      regulating transcription factor which is the hypoxia induced HIF-1alpha when
      applied against human cancers with hypoxic regions like GBM, bearing potential
      for an effective role in human brain tumour therapeutic strategies. Glycolytic
      inhibitors, when added in controlled doses under hypoxia, lead to a reduced
      accumulation of HIF-1alpha and can function as indirect hypoxia regulated genes
      inhibitors like CA9. These may be used as alternative or in conjunction with
      other direct inhibitors like the sulphonamide derivate compounds, chetomin or
      specific siRNAs, or other different chemical compounds possessing similar
      functionality making them as optimal tools for optimized therapy development in
      cancer treatment, especially against human brain cancer. Further experimental
      analysis towards the tumour stage specific inhibitory CA9 characteristics
      determination are necessary to find the optimal therapeutic solutions among the
      different available modalities; whether they are direct or indirect chemical,
      molecular or natural inhibitors to be able to set up successful treatment
      approaches against the different human tumour diseases.

PMID- 20819066
TI  - Carbonic anhydrase inhibitors developed through 'click tailing'.
AB  - In recent years there has been renewed activity in the literature concerning the
      1,3-dipolar cycloaddition reaction (1,3-DCR) of organic azides (R-N3) with
      alkynes (R'-C=CH) to form 1,2,3-triazoles, i.e. the Huisgen synthesis. The use of
      catalytic Cu(I) leads to a dramatic rate enhancement (up to 10(7)-fold) and
      exclusive synthesis of the 1,4-disubstituted 1,2,3-triazole product. The
      reaction, now referred to as the copper-catalyzed azide-alkyne cycloaddition
      (CuAAC), meets the stringent criteria of a click-reaction in that it is modular,
      wide in scope, high yielding, has no byproducts, operates in water at ambient
      temperature, product purification is simple and the starting materials are
      readily available. The 1,3-DCR reaction has rapidly become the premier click
      chemistry reaction with applications spanning modern chemistry disciplines,
      including medicinal chemistry. Recently the 'tail' approach initiative for the
      development of carbonic anhydrase inhibitors (CAIs) has been combined with the
      synthetic versatility of click chemistry. This has proven a powerful combination
      leading to the synthesis of CAIs with useful biopharmaceutical properties and
      activities. This review will discuss complementary and contrasting applications
      that have utilized 'click tailing' for the development of CAIs. Applications
      encompass i) medicinal chemistry and drug discovery; ii) radiopharmaceutical
      development of positron emission topography (PET) chemical probes; and iii) in
      situ click chemistry.

PMID- 20819067
TI  - Carbonic anhydrase related protein VIII and its role in neurodegeneration and
      cancer.
AB  - Mammalian carbonic anhydrase (alpha-CA) gene family comprises sixteen isoforms,
      thirteen of which are active isozymes and three isoforms lack classical CA
      activity of reversible hydration of CO(2) due to absence of one or more histidine
      residues required for CA catalytic activity. The inactive isoforms are known as
      carbonic anhydrase related proteins (CARPs) VIII, X and XI. Among these three,
      CARP VIII was reported first in 1990 from a mouse brain cDNA library and is well
      studied structurally as well as functionally compared to CARP X and XI. CARP VIII
      is an intriguing protein and is widely distributed and evolutionarily well
      conserved across the species. It is mainly expressed in the Purkinje cells of
      cerebellum and in wide variety of other tissues both in mouse and human. CARP
      VIII has been linked to development of colorectal and lung cancers in humans, and
      overexpression of CARP VIII has been observed in several other cancers. A
      mutation in the CA8 gene has been associated with ataxia, mild mental retardation
      and quadrupedal gait in humans and with lifelong gait disorder in mice,
      suggesting an important role for CARP VIII in the brain. However, the precise
      function of CARP VIII is still an enigma. The present review article describes
      the previous data on CARP VIII, including its structure, role in
      neurodegeneration and cancer; and bioinformatic and expression analyses recently
      performed in our laboratory.

PMID- 20819068
TI  - Carbonic anhydrase IX as an anticancer therapy target: preclinical evaluation of
      internalizing monoclonal antibody directed to catalytic domain.
AB  - Carbonic anhydrase IX (CA IX) is a suitable target for various anticancer
      strategies. It is a cell surface protein that is present in human tumors, but not
      in the corresponding normal tissues. Expression of CA IX is induced by hypoxia
      and correlates with cancer prognosis in many tumor types. Moreover, CA IX is
      functionally implicated in cancer progression as a pro-survival factor protecting
      cancer cells against hypoxia and acidosis via its capability to regulate pH and
      cell adhesion. Cancer-related distribution of CA IX allows for targeting cancer
      cells by antibodies binding to its extracellular domain, whereas functional
      involvement of CA IX opens the possibility to hit cancer cells by blocking their
      adaptation to physiologic stresses via inhibition of CA IX enzyme activity. The
      latter strategy is recently receiving considerable attention and great efforts
      are made to produce CA IX-selective inhibitor derivatives with anticancer
      effects. On the other hand, targeting CA IX-expressing cells by immunotherapy has
      reached clinical trials and is close to application in treatment of renal cell
      carcinoma patients. Nevertheless, development and characterization of new CA IX
      specific antibodies is still ongoing. Here we describe a mouse monoclonal
      antibody VII/20 directed to catalytic domain of CA IX. We show that upon binding
      to CA IX, the VII/20 MAb undergoes efficient receptor-mediated internalization,
      which is a process regulating abundance and signaling of cell surface proteins
      and has considerable impact on immunotherapy. We evaluated biological properties
      of the MAb and demonstrated its capacity to elicit anti-cancer effect in mouse
      xenograft model of colorectal carcinoma. Thus, the VII/20 MAb might serve as a
      tool for preclinical studies of immunotherapeutic strategies against non-RCC
      tumors. These have not been explored so far and include broad spectrum of cancer
      types, treatment of which might benefit from CA IX-mediated targeting.

PMID- 20819069
TI  - Recent advances in structural studies of the carbonic anhydrase family: the
      crystal structure of human CA IX and CA XIII.
AB  - The carbonic anhydrase (CA) family has recently become an important target for
      the drug design of inhibitors with potential use as diagnostic and therapeutic
      tools. However, given the high degree of sequence and structure similarity among
      the different CA isoforms, no CA-directed drug developed so far has displayed
      selectivity for a specific isozyme. Since X-Ray crystallography is a very useful
      tool for the rational drug design of selective enzyme inhibitors, in recent years
      extensive research efforts have been devoted to the structural studies of all
      catalytically active &alpha;-CA isoforms, with the consequent resolution of the
      crystallographic structures of nearly all such enzyme isoforms. In this paper we
      review the progress that has recently been made in this field. In particular, we
      summarize the main structural features of hCA XIII and hCA IX, the most recently
      characterized human CA isoforms, and recapitulate how 3D structures of these
      enzymes, together with kinetic experiments, have been used either to deepen our
      knowledge on the structural features responsible of the catalytic properties of
      this protein family or to obtain important information for the rational drug
      design of inhibitors with better selectivity properties.

PMID- 20819070
TI  - Carbonic anhydrase inhibition/activation: trip of a scientist around the world in
      the search of novel chemotypes and drug targets.
AB  - Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes which catalyze CO(2)
      hydration to bicarbonate and protons. Five genetically distinct classes are
      known, which represent an excellent example of convergent evolution. Inhibition
      of alpha-CAs from vertebrates, including humans, with sulfonamides was exploited
      clinically for decades for various classes of diuretics and systemically acting
      antiglaucoma agents, whereas newer inhibitors are used as topically acting
      antiglaucoma drugs, anticonvulsants, antiobesity, antipain and antitumor
      agents/diagnostic tools. Recently, novel interesting chemotypes, in addition to
      the sulfonamides and sulfamates were discovered, such as the phenols,
      coumarins/thiocoumarins/lacosamide, fullerenes, boronic acids and some protein
      tyrosine kinase inhibitors. Furthermore, their detailed mechanism of inhibition
      has been explained and can be used for the rational drug design of other agents.
      Such new classes of enzyme inhibitors show promise for designing interesting
      pharmacological agents and understanding in detail protein-drug interactions at
      molecular level. CAs belonging to the alpha-, beta-, gamma-, delta- and zeta
      families found in many organisms all over the phylogenetic tree and their
      inhibition were studied ultimately in nematodes, corals, some pathogenic protozoa
      (Plasmodium falciparum), fungi/yeasts (Cryptococcus neoformans, Candida albicans,
      C. glabrata, Saccharomyces cerevisiae) and bacteria (Helicobacter pylori,
      Mycobacterium tuberculosis, Brucella suis, Streptococcus pneumoniae), being
      demonstrated that anti-infectives based on their inhibitors might be obtained.
      Possible applications for these new chemotypes are envisaged and discussed in
      detail, based on a chemo-geographical approach which took the author around the
      world and the chemical space.

PMID- 20819071
TI  - Vitamin D and metabolic syndrome: is there a link?
AB  - In addition to bone homeostasis, vitamin D is involved in the physiological
      functions of several tissues and its insufficiency may contribute to various
      disorders. Vitamin D status seems to be associated with each of the components of
      metabolic syndrome (MetS), as well as MetS overall. We review these associations
      as well as the effects of vitamin D supplementation on MetS.

PMID- 20819072
TI  - Proteasome inhibition induces developmentally deregulated programs of apoptotic
      and autophagic cell death during Drosophila melanogaster oogenesis.
AB  - Ubiquitin/proteasome-mediated degradation of eukaryotic proteins is critically
      implicated in a number of signalling pathways and cellular processes. To
      specifically impair proteasome activities, in vitro developing Drosophila
      melanogaster egg chambers were exposed to the MG132 or epoxomicin proteasome
      inhibitors, while a GAL4/UAS binary genetic system was employed to generate
      double transgenic flies overexpressing beta2 and beta6 conditional mutant
      proteasome subunits in a cell type-specific manner. MG132 and epoxomicin
      administration resulted in severe deregulation of in vitro developing egg
      chambers, which was tightly associated with precocious induction of nurse cell
      specific apoptotic and autophagic death programmes, featured by actin
      cytoskeleton disorganization, nuclear chromatin condensation, DRICE caspase
      activation and autophagosome accumulation. In vivo targeted overexpression of
      beta2 and beta6 conditional mutants, specifically in the nurse cell compartment,
      led to a notable up-regulation of sporadic apoptosis potency during early and mid
      oogenesis 'checkpoints', thus reasonably justifying the observed reduction in
      eclosion efficiency. Furthermore, in response to the intracellular abundance of
      beta2 and beta6 conditional mutant forms, specifically in numerous tissues of
      third instar larval stage, the developmental course was arrested, and lethal
      phenotypes were obtained at this particular embryonic period, with the double
      transgenic heterozygote embryos being unable to further proceed to complete
      maturation to adult flies. Our data demonstrate that physiological proteasome
      function is required to ensure normal oogenesis and embryogenesis in D.
      melanogaster, since targeted and cell type-dependent proteasome inactivation
      initiates developmentally deregulated apoptotic and autophagic mechanisms.

PMID- 20819073
TI  - Characterization of a novel peroxisome membrane protein essential for conversion
      of isopenicillin N into cephalosporin C.
AB  - The mechanisms of compartmentalization of intermediates and secretion of
      penicillins and cephalosporins in beta-lactam antibiotic-producing fungi are of
      great interest. In Acremonium chrysogenum, there is a compartmentalization of the
      central steps of the CPC (cephalosporin C) biosynthetic pathway. In the present
      study, we found in the 'early' CPC cluster a new gene named cefP encoding a
      putative transmembrane protein containing 11 transmembrane spanner. Targeted
      inactivation of cefP by gene replacement showed that it is essential for CPC
      biosynthesis. The disrupted mutant is unable to synthesize cephalosporins and
      secretes a significant amount of IPN (isopenicillin N), indicating that the
      mutant is blocked in the conversion of IPN into PenN (penicillin N). The
      production of cephalosporin in the disrupted mutant was restored by
      transformation with both cefP and cefR (a regulatory gene located upstream of
      cefP), but not with cefP alone. Fluorescence microscopy studies with an EGFP
      (enhanced green fluorescent protein)-SKL (Ser-Lys-Leu) protein (a peroxisomal
      targeted marker) as a control showed that the red-fluorescence-labelled CefP
      protein co-localized in the peroxisomes with the control peroxisomal protein. In
      summary, CefP is a peroxisomal membrane protein probably involved in the import
      of IPN into the peroxisomes where it is converted into PenN by the two-component
      CefD1/CefD2 protein system.

PMID- 20819074
TI  - The Friedreich's ataxia protein frataxin modulates DNA base excision repair in
      prokaryotes and mammals.
AB  - DNA-repair mechanisms enable cells to maintain their genetic information by
      protecting it from mutations that may cause malignant growth. Recent evidence
      suggests that specific DNA-repair enzymes contain ISCs (iron-sulfur clusters).
      The nuclearencoded protein frataxin is essential for the mitochondrial
      biosynthesis of ISCs. Frataxin deficiency causes a neurodegenerative disorder
      named Friedreich's ataxia in humans. Various types of cancer occurring at young
      age are associated with this disease, and hence with frataxin deficiency. Mice
      carrying a hepatocyte-specific disruption of the frataxin gene develop multiple
      liver tumours for unresolved reasons. In the present study, we show that frataxin
      deficiency in murine liver is associated with increased basal levels of oxidative
      DNA base damage. Accordingly, eukaryotic V79 fibroblasts overexpressing human
      frataxin show decreased basal levels of these modifications, while prokaryotic
      Salmonella enterica serotype Typhimurium TA104 strains transformed with human
      frataxin show decreased mutation rates. The repair rates of oxidative DNA base
      modifications in V79 cells overexpressing frataxin were significantly higher than
      in control cells. Lastly, cleavage activity related to the ISC-independent repair
      enzyme 8-oxoguanine glycosylase was found to be unaltered by frataxin
      overexpression. These findings indicate that frataxin modulates DNA-repair
      mechanisms probably due to its impact on ISC-dependent repair proteins, linking
      mitochondrial dysfunction to DNA repair and tumour initiation.

PMID- 20819075
TI  - Ectodomain shedding of the Notch ligand Jagged1 is mediated by ADAM17, but is not
      a lipid-raft-associated event.
AB  - Notch signalling is an evolutionarily conserved pathway involved in cell-fate
      specification. The initiating event in this pathway is the binding of a Notch
      receptor to a DSL (Delta/Serrate/Lag-2) ligand on neighbouring cells triggering
      the proteolytic cleavage of Notch within its extracellular juxtamembrane region;
      a process known as proteolytic 'shedding' and catalysed by members of the ADAM (a
      disintegrin and metalloproteinase) family of enzymes. Jagged1 is a Notch-binding
      DSL ligand which is also shed by an ADAM-like activity raising the possibility of
      bi-directional cell-cell Notch signalling. In the present study we have
      unequivocally identified the sheddase responsible for shedding Jagged1 as ADAM17,
      the activity of which has previously been shown to be localized within
      specialized microdomains of the cell membrane known as 'lipid rafts'. However, we
      have shown that replacing the transmembrane and cytosolic regions of Jagged1 with
      a GPI (glycosylphosphatidylinositol) anchor, thereby targeting the protein to
      lipid rafts, did not enhance its shedding. Furthermore, the Jagged1 holoprotein,
      its ADAM-cleaved C-terminal fragment and ADAM17 were not enriched in raft
      preparations devoid of contaminating non-raft proteins. We have also demonstrated
      that wild-type Jagged1 and a truncated polypeptide-anchored variant lacking the
      cytosolic domain were subject to similar constitutive and phorbol ester-regulated
      shedding. Collectively these data demonstrate that Jagged1 is shed by ADAM17 in a
      lipid-raft-independent manner, and that the cytosolic domain of the former
      protein is not a pre-requisite for either constitutive or regulated shedding.

PMID- 20819076
TI  - Interaction with receptor for activated C-kinase 1 (RACK1) sensitizes the
      phosphodiesterase PDE4D5 towards hydrolysis of cAMP and activation by protein
      kinase C.
AB  - We have previously identified the PKC (protein kinase C)-anchoring protein RACK1
      (receptor for activated C-kinase 1), as a specific binding partner for the cAMP
      specific phosphodiesterase PDE4D5, suggesting a potential site for cross-talk
      between the PKC and cAMP signalling pathways. In the present study we found that
      elevation of intracellular cAMP, with the beta2-adrenoceptor agonist
      isoproterenol (isoprenaline), led to activation of PDE4 enzymes in the
      particulate and soluble fractions of HEK (human embryonic kidney)-293 cells. In
      contrast activation of PDE4D5, with isoproterenol and the PKC activator PMA, was
      restricted to the particulate fraction, where it interacts with RACK1; however,
      RACK1 is dispensable for anchoring PDE4D5 to the particulate fraction. Kinetic
      studies demonstrated that RACK1 alters the conformation of particulate-associated
      PDE4D5 so that it more readily interacts with its substrate cAMP and with
      rolipram, a PDE4 inhibitor that specifically targets the active site of the
      enzyme. Interaction with RACK1 was also essential for PKC-dependent and ERK
      (extracellular-signal-regulated kinase)-independent phosphorylation (on Ser126),
      and activation of PDE4D5 in response to PMA and isoproterenol, both of which
      trigger the recruitment of PKCalpha to RACK1. Together these results reveal novel
      signalling cross-talk, whereby RACK1 mediates PKC-dependent activation of PDE4D5
      in the particulate fraction of HEK-293 cells in response to elevations in
      intracellular cAMP.

PMID- 20819077
TI  - Two routes of iron accumulation in astrocytes: ascorbate-dependent ferrous iron
      uptake via the divalent metal transporter (DMT1) plus an independent route for
      ferric iron.
AB  - Astrocytes are central to iron and ascorbate homoeostasis within the brain.
      Although NTBI (non-transferrin-bound iron) may be a major form of iron imported
      by astrocytes in vivo, the mechanisms responsible remain unclear. The present
      study examines NTBI uptake by cultured astrocytes and the involvement of
      ascorbate and DMT1 (divalent metal transporter 1). We demonstrate that iron
      accumulation by ascorbate-deficient astrocytes is insensitive to both membrane
      impermeant Fe(II) chelators and to the addition of the ferroxidase
      caeruloplasmin. However, when astrocytes are ascorbate-replete, as occurs in
      vivo, their rate of iron accumulation is doubled. The acquisition of this
      additional iron depends on effluxed ascorbate and can be blocked by the DMT1
      inhibitor ferristatin/NSC306711. Furthermore, the calcein-accessible component of
      intracellular labile iron, which appears during iron uptake, appears to consist
      of only Fe(III) in ascorbate-deficient astrocytes, whereas that of ascorbate
      replete astrocytes comprises both valencies. Our data suggest that an Fe(III)
      uptake pathway predominates when astrocytes are ascorbate-deficient, but that in
      ascorbate-replete astrocytes, at least half of the accumulated iron is initially
      reduced by effluxed ascorbate and then imported by DMT1. These results suggest
      that ascorbate is intimately involved in iron accumulation by astrocytes, and is
      thus an important contributor to iron homoeostasis in the mammalian brain.

PMID- 20819078
TI  - MicroRNA-7 targets IGF1R (insulin-like growth factor 1 receptor) in tongue
      squamous cell carcinoma cells.
AB  - miR-7 (microRNA-7) has been characterized as a tumour suppressor in several human
      cancers. It targets a number of proto-oncogenes that contribute to cell
      proliferation and survival. However, the mechanism(s) by which miR-7 suppresses
      tumorigenesis in TSCC (tongue squamous cell carcinoma) is unknown. The present
      bioinformatics analysis revealed that IGF1R (insulin-like growth factor 1
      receptor) mRNA is a potential target for miR-7. Ectopic transfection of miR-7 led
      to a significant reduction in IGF1R at both the mRNA and protein levels in TSCC
      cells. Knockdown of miR-7 in TSCC cells enhanced IGF1R expression. Direct
      targeting of miR-7 to three candidate binding sequences located in the 3'
      untranslated region of IGF1R mRNA was confirmed using luciferase-reporter-gene
      assays. The miR-7-mediated down-regulation of IGF1R expression attenuated the
      IGF1 (insulin-like growth factor 1)-induced activation of Akt (protein kinase B)
      in TSCC cell lines, which in turn resulted in a reduction in cell proliferation
      and cell-cycle arrest, and an enhanced apoptotic rate. Taken together, the
      present results demonstrated that miR-7 regulates the IGF1R/Akt signalling
      pathway by post-transcriptional regulation of IGF1R. Our results indicate that
      miR-7 plays an important role in TSCC and may serve as a novel therapeutic target
      for TSCC patients.

PMID- 20819080
TI  - Akt inhibitors reduce glucose uptake independently of their effects on Akt.
AB  - The protein kinase Akt is involved in various cellular processes, including cell
      proliferation, growth and metabolism. Hyperactivation of Akt is commonly observed
      in human tumours and so this pathway has been the focus of targeted drug
      discovery. However, Akt also plays an essential role in other physiological
      processes, such as the insulin-regulated transport of glucose into muscle and fat
      cells. This process, which is essential for whole-body glucose homoeostasis in
      mammals, is thought to be mediated via Akt-dependent movement of GLUT4 glucose
      transporters to the plasma membrane. In the present study, we have investigated
      the metabolic side effects of non-ATP-competitive allosteric Akt inhibitors. In
      3T3-L1 adipocytes, these inhibitors caused a decrease in the Akt signalling
      pathway concomitant with reduced glucose uptake. Surprisingly, a similar
      reduction in GLUT4 translocation to the plasma membrane was not observed. Further
      investigation revealed that the inhibitory effects of these compounds on glucose
      uptake in 3T3-L1 adipocytes were independent of the Akt signalling pathway. The
      inhibitors also inhibited glucose transport into other cell types, including
      human erythrocytes and T-47D breast cancer cells, suggesting that these effects
      are not specific to GLUT4. We conclude that these drugs may, at least in part,
      inhibit tumorigenesis through inhibition of tumour cell glucose transport.

PMID- 20819079
TI  - Unique functions for protein kinase D1 and protein kinase D2 in mammalian cells.
AB  - Mammalian PKD (protein kinase D) isoforms have been implicated in the regulation
      of diverse biological processes in response to diacylglycerol and PKC (protein
      kinase C) signalling. To compare the functions of PKD1 and PKD2 in vivo, we
      generated mice deficient in either PKD1 or PKD2 enzymatic activity, via
      homozygous expression of PKD1(S744A/S748A) or PKD2(S707A/S711A) 'knockin'
      alleles. We also examined PKD2-deficient mice generated using 'gene-trap'
      technology. We demonstrate that, unlike PKD1, PKD2 catalytic activity is
      dispensable for normal embryogenesis. We also show that PKD2 is the major PKD
      isoform expressed in lymphoid tissues, but that PKD2 catalytic activity is not
      essential for the development of mature peripheral T- and B-lymphocytes. PKD2
      catalytic activity is, however, required for efficient antigen receptor-induced
      cytokine production in T-lymphocytes and for optimal T-cell-dependent antibody
      responses in vivo. Our results reveal a key in vivo role for PKD2 in regulating
      the function of mature peripheral lymphocytes during adaptive immune responses.
      They also confirm the functional importance of PKC-mediated serine
      phosphorylation of the PKD catalytic domain for PKD activation and downstream
      signalling and reveal that different PKD family members have unique and non
      redundant roles in vivo.

PMID- 20819081
TI  - Long-term results of bilateral congenital cataract treated with early cataract
      surgery, aphakic glasses and secondary IOL implantation.
AB  - PURPOSE: To evaluate the long-term visual outcome after early surgery of
      bilateral dense congenital cataracts, aphakic correction with glasses and
      secondary intraocular lens (IOL) implantation around 2 years of age. METHODS: The
      medical records of paediatric patients who underwent cataract extraction, aphakic
      correction and secondary IOL implantation from 1993 to 2004 at Seoul National
      University Children's Hospital were reviewed retrospectively. Age at secondary
      IOL implantation, axial length (AL), best corrected visual acuity (BCVA),
      refractive error, ocular alignment, stereopsis, and postoperative ocular
      complications were recorded. RESULTS: Thirty-seven paediatric bilateral
      pseudophakic patients were identified with a mean follow-up period of 81.4
      months. Best corrected visual acuity of 20/40 or better were attained in 44.0% of
      eyes, and the median BCVA was 20/50. Preoperative factors associated with poor
      visual prognosis included cataract surgery after 8 weeks of age, interocular AL
      difference of 0.5 mm or more, and glaucoma. Amblyopic eyes showed more myopic
      change compared to fellow eyes. Good or moderate binocular function was achieved
      in 18.9% of all patients. Incidences of strabismus, glaucoma, posterior capsular
      opacity formation were 46.0%, 32.4% and 4.0%, respectively. CONCLUSION: Good
      postoperative BCVA and binocular function were achieved in most healthy children
      with bilateral dense congenital cataract and no posterior segment pathology.
      Early cataract surgery, aphakic correction with glasses and secondary IOL
      implantation around 2 years of age appears to be appropriate methods.

PMID- 20819082
TI  - Immediate versus delayed quitting and rates of relapse among smokers treated
      successfully with varenicline, bupropion SR or placebo.
AB  - AIMS: We assessed to what degree smokers who fail to quit on the target quit date
      (TQD) or lapse following TQD eventually achieve success with continued treatment.
      DESIGN: A secondary analysis of pooled data of successful quitters treated with
      varenicline (306 of 696), bupropion (199 of 671) and placebo (121 of 685) from
      two identically-designed clinical trials of varenicline versus bupropion
      sustained-release and placebo. SETTING: Multiple research centers in the US.
      PARTICIPANTS: Adult smokers (n==2052) randomized to 12 weeks drug treatment plus
      40 weeks follow-up. MEASUREMENT: The primary end-point for the trials was
      continuous abstinence for weeks 9-12. TQD was day 8. Two patterns of successful
      quitting were identified. Immediate quitters (IQs) were continuously abstinent
      for weeks 2-12. Delayed quitters (DQs) smoked during 1 or more weeks for weeks 2
      8. FINDINGS: Cumulative continuous abstinence (IQs + DQs) increased for all
      treatments during weeks 3-8. Overall IQs and DQs for varenicline were (24%; 20%)
      versus bupropion (18.0%, P=0.007; 11.6%, P<0.001) or placebo (10.2%, P<0.001;
      7.5%, P<0.001). However, DQs as a proportion of successful quitters was similar
      for all treatments (varenicline 45%; bupropion 39%; placebo 42%) and accounted
      for approximately one-third of those remaining continuously abstinent for weeks 9
      52. No gender differences were observed by quit pattern. Post-treatment relapse
      was similar across groups. CONCLUSIONS: Our data support continuing cessation
      treatments without interruption for smokers motivated to remain in the quitting
      process despite lack of success early in the treatment.

PMID- 20819084
TI  - The hypothetical role of FoxO1 in acne is interesting, but more study is needed
      before any conclusions can be drawn.

PMID- 20819085
TI  - A prospective case-controlled cohort study of endothelial function in patients
      with moderate to severe psoriasis.
AB  - BACKGROUND: There is well-documented evidence that patients with moderate and
      severe psoriasis have a significantly increased risk of cardiovascular disease
      (CVD). While this risk can, at least in part, be attributed to the high
      prevalence of traditional risk factors in the population with psoriasis, some
      epidemiological evidence suggests it may be independent of these. OBJECTIVES:
      This prospective, case-controlled study investigates whether psoriasis is a risk
      factor for CVD using two, validated, sensitive markers of CVD, endothelial
      dysfunction and high-sensitivity C-reactive protein (hsCRP). METHODS: Patients
      were recruited from a tertiary referral psoriasis clinic and exclusion criteria
      included established CVD and/or conventional risks for CVD. Preclinical CVD was
      assessed using flow-mediated brachial artery dilatation, which measures
      endothelial dysfunction, and hsCRP, a serological marker of atherosclerosis.
      RESULTS: Sixty-four patients (22%) out of a total of 285 consecutive patients
      attending the severe psoriasis clinic were entered into the study. One hundred
      and sixty-one (56%) were excluded following identification of cardiovascular
      risk; 39 of the 161 (24%) had at least two cardiovascular risk factors. A further
      16 (6%) patients were excluded because of established CVD. No statistically
      significant difference in endothelial dysfunction was observed between patients
      with psoriasis (n = 60) and healthy controls (n = 117) (P = 0.508). The hsCRP
      level was, however, significantly elevated in the psoriasis group (2.828 mg L(
      1), SEM 0.219; controls 0.728 mg L(-1), SEM 0.142; P < 0.05). CONCLUSION: This
      large, investigative study is the first to assess endothelial function in
      patients with psoriasis after exclusion of traditional risk factors for CVD.
      These data suggest that psoriasis per se is not a risk factor for CVD and that
      elevated hsCRP is possibly independent of atheroma risk. There was a high
      prevalence of traditional risk factors in our population with severe psoriasis.

PMID- 20819086
TI  - Efficacy and tolerability of proactive treatment with topical corticosteroids and
      calcineurin inhibitors for atopic eczema: systematic review and meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Long-term low-level topical anti-inflammatory therapy has been
      suggested as a new paradigm in the treatment of atopic eczema (AE). OBJECTIVES:
      To determine the efficacy and tolerability of topical corticosteroids and
      calcineurin inhibitors for flare prevention in AE. METHODS: Systematic review of
      randomized controlled trials reporting efficacy of topical corticosteroids and/or
      topical calcineurin inhibitors for flare prevention in AE. Identification of
      relevant articles by systematic electronic searches (Cochrane Library, Medline)
      supplemented by hand search. Primary efficacy endpoint: proportion of
      participants experiencing at least one flare during proactive anti-inflammatory
      treatment. Relative risks (RRs) and corresponding 95% confidence intervals (CIs)
      were calculated and pooled by pharmaceutical agent using random-effects meta
      analysis. Sensitivity analysis included meta-regression to explore the influence
      of study-specific covariates. RESULTS: Nine articles reporting on eight vehicle
      controlled trials were included. Three, four and one trial(s) evaluated proactive
      therapy with topical tacrolimus, fluticasone propionate and methylprednisolone
      aceponate, respectively. Each agent under study was more efficacious to prevent
      flares than vehicle. Meta-analysis suggested that topical fluticasone propionate
      (RR 0.46, 95% CI 0.38-0.55) may be more efficacious to prevent disease flares
      than topical tacrolimus (RR 0.78, 95% CI 0.60-1.00). Meta-regression indicated
      robustness of these findings. Proactive anti-inflammatory therapy was generally
      well tolerated. The trials identified, however, do not allow firm conclusions
      about long-term safety. CONCLUSIONS: Vehicle-controlled trials indicate efficacy
      of proactive treatment with tacrolimus, fluticasone propionate and
      methylprednisolone aceponate to prevent AE flares. Indirect evidence from vehicle
      controlled trials suggests that twice weekly application of the potent topical
      corticosteroid fluticasone propionate may be more efficacious to prevent AE
      flares than tacrolimus ointment. Head to head trials should be conducted to
      confirm these results. Future studies are also needed to evaluate the long-term
      safety of proactive treatment of AE.

PMID- 20819087
TI  - Efficacy and tolerability of rupatadine at four times the recommended dose
      against histamine- and platelet-activating factor-induced flare responses and ex
      vivo platelet aggregation in healthy males.
AB  - BACKGROUND: European guidelines recommend increasing H1-antihistamine doses up to
      fourfold in poorly responding patients with urticaria. OBJECTIVES: To assess the
      efficacy and tolerability of high-dose rupatadine (40 mg) against platelet
      activating factor (PAF)- and histamine-induced flare responses in human skin and
      to verify its anti-PAF activity by assessing its inhibition of PAF-induced
      platelet aggregation in the blood of subjects receiving rupatadine 40 mg.
      METHODS: In the flare study, six male volunteers received a single dose of
      rupatadine 40 mg. Flares were induced before dosing and up to 96 h afterwards by
      intradermal PAF and histamine. In the ex vivo study, four male volunteers
      received an oral dose of rupatadine 40 mg and blood samples were taken 4 h
      afterwards. Platelet aggregation was assessed in platelet-rich plasma by
      incubation for 5 min with PAF. RESULTS: Rupatadine 40 mg reached maximal plasma
      levels of 15.1 +/- 4.4 ng mL-1)1 at 1 h and its metabolite, desloratadine, 5.2 +/
      0.9 ng mL-1)1 at 2 h. Neither was detectable at 12 h. Inhibition of histamine-
      and PAF-induced flares was significant within 2 h, maximal at 6 h (87.8 +/- 3.1%
      and 87.1 +/- 2.5% inhibition, respectively, P < 0.0001) and still statistically
      significant at 72 h. Rupatadine 40 mg inhibited PAF-induced platelet aggregation
      ex vivo by 82 +/- 9% (P = 0.023). A single oral dose of rupatadine 40 mg was well
      tolerated with mild transient somnolence being reported. CONCLUSIONS: A single
      dose of rupatadine at four times the recommended dose is well tolerated, highly
      effective for up to 72 h against PAF- and histamine-induced dermal flares and has
      demonstrable PAF-receptor antagonism ex vivo.

PMID- 20819088
TI  - Reversible relapse of pemphigus foliaceus triggered by topical imiquimod suggests
      that Toll-like receptor 7 inhibitors may be useful treatments for pemphigus.

PMID- 20819089
TI  - Serum transforming growth factor beta1 during diabetes development in non-obese
      diabetic mice and humans.
AB  - Recent data show that regulatory cells with transforming growth factor (TGF)
      beta1-dependent activity are able to restore self-tolerance in overtly diabetic
      non-obese diabetic (NOD) mice. Thus, TGF-beta1 seems to have a relevant role in
      protection from autoimmune diabetes. Our aim was to investigate the possible
      significance of serum TGF-beta1 measurement in the natural history of diabetes in
      NOD mice, as well as in children positive for at least one islet-related
      antibody. Serum TGF-beta1 (both total and active) was measured by enzyme-linked
      immunosorbent assay at monthly intervals in 26 NOD mice during the spontaneous
      development of diabetes and, on a yearly basis, in nine siblings of patients with
      type 1 diabetes (T1D) with a follow-up of 4 years. Diabetes appeared between the
      12th week of age and the end of the study period (36 weeks) in 17 mice. TGF-beta1
      serum level variations occurred in the prediabetic period in both NOD mice and
      humans and diabetes diagnosis followed a continuing reduction of active TGF-beta1
      (aTGF-beta1) serum levels. In mice, aTGF-beta1 serum levels measured at 4 weeks
      of age correlated positively with severity of insulitis, and negatively with
      percentage of insulin-positive cells. Our findings suggest that in NOD mice serum
      TGF-beta1 levels during the natural history of the diabetes reflect the course of
      islet inflammation. The measurement of aTGF-beta1 in islet-related antibody
      positive subjects may provide insights into the natural history of prediabetic
      phase of T1D.

PMID- 20819090
TI  - In vitro exposure of human fibroblasts to local anaesthetics impairs cell growth.
AB  - Lidocaine, bupivacaine or ropivacaine are used routinely to manage perioperative
      pain. Sparse data exist evaluating the effects of local anaesthetics (LA) on
      fibroblasts, which are involved actively in wound healing. Therefore, we
      investigated the effects of the three LA to assess the survival, viability and
      proliferation rate of fibroblasts. Human fibroblasts were exposed to 0.3 mg/ml
      and 0.6 mg/ml of each LA for 2 days, followed by incubation with normal medium
      for another 1, 4 or 7 days (group 1). Alternatively, cells were incubated
      permanently with LA for 3, 6 or 9 days (group 2). Live cell count was assessed
      using trypan blue staining. Viability was measured by the tetrazolium bromide
      assay. Proliferation tests were performed with the help of the colorimetric
      bromodeoxyuridine assay. Production of reactive oxygen species (ROS) was
      determined, measuring the oxidation of non-fluorescent-2,7'-dichlorofluorescin.
      Treatment of cells with the three LA showed a concentration-dependent decrease of
      live cells, mitochondrial activity and proliferation rate. Group arrangement
      played a significant role for cell count and proliferation, while exposure time
      influenced viability. Among the analysed LA, bupivacaine showed the most severe
      cytotoxic effects. Increased production of ROS correlated with decreased
      viability of fibroblasts in lidocaine- and bupivacaine-exposed cells, but not
      upon stimulation with ropivacaine. This study shows a concentration-dependent
      cytotoxic effect of lidocaine, bupivacaine and ropivacaine on fibroblasts in
      vitro, with more pronounced effects after continuous incubation. A possible
      mechanism of cell impairment could be triggered by production of ROS upon
      stimulation with lidocaine and bupivacaine.

PMID- 20819091
TI  - The dendritic cell mannose receptor mediates allergen internalization and
      maturation involving notch 1 signalling.
AB  - Dendritic cells (DCs) have been shown recently to play a key role in inducing and
      mediating T helper type 2 (Th2) responses associated with atopic disease. These
      responses are mediated in part by ligation to different Toll-like receptors
      (TLRs) and C-type lectins, e.g. the mannose receptor (MR), depending upon the DC
      subset involved and the respective microenvironments. Because ovalbumin (OVA)
      (which is structurally related to various allergens) can engage the MR, we can
      use OVA stimulation as a model for understanding the roles of both TLRs and the
      MR in allergic inflammatory responses. We examined TLR- and MR-mediated responses
      from mouse bone marrow-derived DCs in the context of antigen recognition and
      presentation in addition to examining the relationship between notch 1, TLRs and
      MR signalling pathways. This work demonstrated that OVA-mediated signalling up
      regulated both TLR-2 and MR and that MR RNA interference (RNAi) but not TLR2 RNAi
      inhibited DC internalization of fluorescein isothiocyanate-OVA. Furthermore, MR
      RNAi inhibited OVA- and house dust mite allergen extract-induced DC maturation
      and MR RNAi and TLR2 RNAi influenced DC interleukin-12 production independently.
      Finally, we demonstrated that blocking notch 1 signalling inhibited both notch 1
      and TLR-2 expression but not MR expression levels. However, MR RNAi inhibited the
      expression of MR, TLR-2 and notch 1. These results indicate that MR is the
      primary receptor mediating the internalization of environmental allergen
      glycoproteins. In addition, TLR-2 and notch 1 play important roles in DC
      maturation and antigen presentation and signals originating from the MR and TLR-2
      receptors converge with the notch 1 signalling pathway.

PMID- 20819092
TI  - The inhibitory effects of intravenous administration of rabbit immunoglobulin G
      on airway inflammation are dependent upon Fcgamma receptor IIb on CD11c(+)
      dendritic cells in a murine model.
AB  - Immunoglobulins (Igs) play important immunomodulatory effects on allergic asthma.
      Among these, IgG has been reported to regulate allergic inflammation in previous
      studies about immunotherapy and intravenous immunoglobulin therapy. In this
      study, to examine the immunomodulatory mechanisms of IgG and FcRs we evaluated
      the effects of intravenous (i.v.) rabbit IgG administration (IVIgG) on allergic
      airway inflammation and lung antigen-presenting cells (APCs) in a murine model of
      ovalbumin (OVA) sensitization and challenge. In OVA-challenged mice, IVIgG
      attenuated airway eosinophilia, airway hyperresponsiveness and goblet cell
      hyperplasia and also inhibited the local T helper type (Th) 2 cytokine levels.
      Additionally, IVIgG attenuated the proliferation of OVA-specific CD4(+) T cells
      transplanted into OVA-challenged mice. Ex vivo co-culture with OVA-specific
      CD4(+) cells and lung CD11c(+) APCs from mice with IVIgG revealed the attenuated
      transcription level of Th2 cytokines, suggesting an inhibitory effect of IVIgG on
      CD11c(+) APCs to induce Th2 response. Next, to analyse the effects on Fcgamma
      receptor IIb and dendritic cells (DCs), asthmatic features in Fcgamma receptor
      IIb-deficient mice were analysed. IVIgG failed to attenuate airway eosinophilia,
      airway inflammation and goblet cell hyperplasia. However, the lacking effects of
      IVIgG on airway eosinophilia in Fcgamma receptor IIb deficiency were restored by
      i.v. transplantation of wild-type bone marrow-derived CD11c(+) DCs. These results
      demonstrate that IVIgG attenuates asthmatic features and the function of lung
      CD11c(+) DCs via Fcgamma receptor IIb in allergic airway inflammation. Targeting
      Fc portions of IgG and Fcgamma receptor IIb on CD11c(+) DCs in allergic asthma is
      a promising therapeutic strategy.

PMID- 20819094
TI  - A new era for Clinical and Experimental Pharmacology and Physiology.

PMID- 20819093
TI  - CCL20 is overexpressed in Mycobacterium tuberculosis-infected monocytes and
      inhibits the production of reactive oxygen species (ROS).
AB  - CCL20 is a chemokine that attracts immature dendritic cells. We show that
      monocytes, cells characteristic of the innate immune response, infected with
      Mycobacterium tuberculosis express the CCL20 gene at a much higher level than the
      same cells infected with non-tuberculous mycobacteria. Interferon (IFN)-gamma, a
      fundamental cytokine in the immune response to tuberculosis, strongly inhibits
      both the transcription and the translation of CCL20. We have also confirmed that
      dendritic cells are a suitable host for mycobacteria proliferation, although
      CCL20 does not seem to influence their intracellular multiplication rate. The
      chemokine, however, down-regulates the characteristic production of reactive
      oxygen species (ROS) induced by M. tuberculosis in monocytes, which may affect
      the activity of the cells. Apoptosis mediated by the mycobacteria, possibly ROS
      dependent, was also inhibited by CCL20.

PMID- 20819095
TI  - Erythropoietin prevents vascular inflammation and oxidative stress in subtotal
      nephrectomized rat aorta beyond haematopoiesis.
AB  - 1. Recombinant human erythropoietin (rHuEPO) has been used for the management of
      renal anaemia. Recent studies suggest pleiotropic properties of rHuEPO in various
      tissues. The aim of the present study was to investigate the vasoprotective
      effects of rHuEPO in renal failure rats. 2. Rats subjected to 5/6 and 17/18
      nephrectomy (5/6Nx and 17/18Nx rats, respectively) were treated with rHuEPO (75
      U/kg, s.c.) three times a week for 2 weeks. 3. Administration of rHuEPO to 5/6Nx
      or 17/18Nx rats had no effect on systolic blood pressure or decreased
      haematocrit. However, rHuEPO treatment normalized proteinuria and creatinine
      clearance in 5/6Nx, but not in 17/18Nx, rats. 4. Vasodilation in response to
      acetylcholine in aortic rings was impaired in 5/6Nx and 17/18Nx rats and improved
      by rHuEPO in both groups. Immunohistochemical analysis revealed that macrophage
      infiltration into adventitial areas and the expression of osteopontin were
      enhanced in aortas from 5/6Nx and 17/18Nx rats, but that rHuEPO suppressed these
      effects. In addition, rHuEPO attenuated medial hyperplasia and NADPH oxidase
      derived superoxide production in 5/6Nx and 17/18Nx rats. 5. Activation of the Akt
      signalling pathway was evident in rHuEPO-treated rats as the increased expression
      of phosphorylated Akt and glycogen synthase kinase-3beta. Treatment with rHuEPO
      restored the expression of phosphorylated endothelial nitric oxide synthase in
      the aorta and urinary excretion of NO(x) in nephrectomized rats. 6. These results
      suggest that a low dose of rHuEPO results in the normalization of endothelial
      function, vascular inflammation and oxidative stress in rats with renal ablation
      beyond haematopoiesis. In addition, these vasoprotective effects are observed
      even in a state of deteriorating renal dysfunction.

PMID- 20819096
TI  - The number of lymph node metastases influences survival and International Union
      Against Cancer tumor-node-metastasis classification for esophageal squamous cell
      carcinoma: does lymph node yield matter?

PMID- 20819097
TI  - Left thoracoabdominal esophagectomy: results from a single specialist center.
AB  - The left thoracoabdominal approach to esophagectomy is not widely performed,
      despite offering excellent exposure to tumors of the esophagogastric junction.
      Criticisms of the approach have focused on historically high rates of mortality,
      complications, and positive resection margins. Our aim was to determine whether
      left thoracoabdominal esophagectomy could combine a radical oncological resection
      with acceptably low mortality and morbidity. A retrospective cohort study of all
      left thoracoabdominal esophagectomies was performed at a single specialist center
      over an 11-year period. Primary outcomes were in-hospital mortality,
      complications, resection margin involvement, and lymph node yield; secondary
      outcomes were 1-year and 5-year survival. Two hundred eleven esophagectomies were
      performed. In-hospital mortality was 5.7% (12/211). One hundred one subjects
      (47.9%) had an uncomplicated recovery; 110 subjects (52.1%) developed at least
      one complication. There were 15 clinically significant anastomotic leaks (7.1%).
      Twenty-four subjects (11.4%) required emergency reoperation, the most common
      indication being anastomotic leakage. Complete tumor excision (R0 resection) was
      achieved in 151 of 211 cases (71.6%); median lymph node yield was 24. One-year
      and 5-year survival rates were 70% (147/211) and 21% (24/116), respectively. Left
      thoracoabdominal esophagectomy can combine a radical oncological resection with
      acceptably low mortality and morbidity.

PMID- 20819098
TI  - Establishment of a novel human esophageal squamous cell carcinoma cell line (ESC
      410) and its partial biological characterization.
AB  - Esophageal cancer exhibits an uneven geographical distribution strikingly,
      resulting in focal endemic high-incidence areas in several countries worldwide
      including China, which might be associated with the environmental and genetic
      risk factors in those areas. Permanent cancer cell lines are invaluable tools in
      understanding the biology of cancers and experimental therapeutics. To enrich
      cell line panel and animal models of human esophageal squamous cell carcinoma
      (ESCC) from different geographical areas and investigate the environmental and
      genetic risk factors in the carcinogenesis of ESCC, a novel human esophageal
      squamous cancer cell line (ESC-410) was established. The cell line grew adherent
      as a monolayer and maintained stable growth rate with a doubling time of 53 h and
      distinct epithelial morphological appearance; it was maintained in vitro for 18
      months and subcultured for more than 50 passages. Ultrastructural examination
      revealed large irregular nuclei, desmosome, and tonofilaments; karyotype analysis
      showed a modal number of chromosomes that ranged from 35 to 73, with a median of
      57, and 77% of analyzed cells were hyperdiploidy; reverse transcription
      polymerase chain reaction (RT-PCR) detected the mRNA expressions of CK8, CK18,
      and CK19 in the established cells; immunofluorescence assay identified the
      protein expressions of neurotrophin receptor p75 and integrin alpha6 (CD49f) in
      the ESC-410 cell line; xenotransplantation of ESC-410 cells into athymic nude
      mice subcutaneously induced the formation of solid tumor masses in about 2 weeks.
      By histopathological examination, heterogeneity of xenograft tumor was observed,
      as same as that of human primary ESCC. All findings and evidence in this
      experimental study suggested that this cell line might be a useful model in vitro
      and in vivo in cellular and molecular studies as well as in testing novel
      therapies for human ESCC.

PMID- 20819099
TI  - Early acid perception in NERD.
AB  - Heartburn is the hallmark of gastroesophageal reflux disease. The hypothesis
      tested in this study is that the time of onset of this symptom may play a role in
      the development of mucosal lesions. During endoscopy of 61 patients complaining
      of heartburn and nine control subjects, gastric fluid was aspirated using a
      catheter introduced through the operative channel, and blindly instilled onto the
      esophageal mucosa before withdrawing the endoscope. Saline was used as control.
      Evocated symptoms and endoscopic lesions were recorded. Thirty-seven patients did
      not present esophageal lesions (nonerosive reflux disease [NERD]); 24 presented
      esophagitis (ERD). Instillation of gastric fluid on the esophageal mucosa
      elicited heartburn in 46% of patients with NERD, 8.3% with ERD, and 11.1% of
      controls. Symptoms lasted throughout the procedure but were no longer present
      when the gastroscope was withdrawn. The NERD value was significantly higher than
      that of ERD (P= 0.02) and controls (P= 0.02), while no difference was found
      between ERD and controls. Saline did not induce symptoms either in controls or
      patients. NERD patients show an early response to gastric fluid instillation much
      more frequently than ERD and controls. It is hypothesized that the early onset of
      symptoms in NERD patients may be a possibility to avoid the progress of mucosal
      lesions by claiming an earlier medical care.

PMID- 20819100
TI  - Health-related quality of life in long-term survivors after high-dose
      chemoradiotherapy followed by surgery in esophageal cancer.
AB  - Curative treatment of esophageal cancer with definitive or preoperative high-dose
      chemoradiotherapy inflicts a major strain on the patients with potentially severe
      physical, emotional, and social consequences. The aim of this study was to assess
      various aspects of quality of life and fatigue in long-term survivors following
      such a treatment. Patients undergoing a potentially curative treatment between
      1996 and 2007, and still alive (n= 41) completed quality of life questionnaires
      of the European Organization for Research and Treatment of Cancer core
      questionnaire (QLQ-C30) and esophageal cancer module (QLQ-OES18). Twenty patients
      were treated by surgery alone, and 21 patients were scheduled for high-dose
      chemoradiotherapy followed by surgery. Five of those patients did not undergo
      planned surgery. Preoperative chemoradiotherapy consisted of three courses of
      chemotherapy, cisplatin 100 mg/m(2) and 5-fluorouracil 5000 mg/m(2) in each
      course and concomitant radiotherapy of a median dose 66 Gy. Quality of life in
      esophageal cancer patients receiving high-dose chemoradiotherapy was compared
      with that for esophageal cancer patients who received only surgery, head and neck
      cancer patients, laryngectomized patients, and a random sample of the general
      Norwegian population. Esophageal cancer patients treated by high-dose
      chemoradiotherapy had significantly worse global quality of life as reflected by
      almost all functional scales and higher fatigue compared with esophageal cancer
      patients who received surgery alone, head and neck cancer patients, and the
      general Norwegian population. There were no significant differences in quality of
      life between the esophageal cancer patients receiving high-dose chemoradiotherapy
      and the laryngectomy patients. Further, the esophageal cancer patients receiving
      high-dose chemoradiotherapy had higher intensity of other symptoms like general
      pain, insomnia, nausea/vomiting, diarrhea, and constipation compared with the
      esophageal cancer patients who received surgery alone, head and neck cancer
      patients, and the general Norwegian population. High-dose chemoradiotherapy with
      cisplatin and 5-fluorouracil had a considerable negative long-term effect on
      global quality of life in patients with resectable esophageal cancer. Fatigue was
      a prominent long-lasting symptom in these patients.

PMID- 20819101
TI  - Esophageal duplication cyst.

PMID- 20819102
TI  - Treatment of intrathoracic anastomotic leak by nose fistula tube drainage after
      esophagectomy for cancer.
AB  - Esophageal anastomotic leak remains a lethal complication after esophagectomy for
      cancer. The aim of the present study is to describe an effective new management,
      nose fistula tube drainage (NFTD), to treat postoperative intrathoracic leaks.
      From July 2003 to August 2009, 41 of 4132 patients (0.99%) requiring
      transthoracic esophagectomy for esophageal and cardiac carcinoma had developed an
      intrathoracic esophageal anastomotic leak in our hospital as well as another
      three patients with similar conditions from other hospitals, excluding three
      patients with gastric necrosis (two) and tracheo-esophageal fistula (one); 23
      patients were treated by NFTD, and the remaining 18 patients were treated by
      conventional chest tube drainage (CCTD). Clinical records of these patients were
      reviewed and analyzed, including the healing of the leak, mortality, and
      morbidity. In the NFTD group, 4 patients (17.4%) died, 1 patient (4.3%) required
      reoperation, and 18 patients (78.3%) healed. However, in the CCTD group, 3
      patients (16.7%) died, 1 patient (5.5%) required reoperation, and 14 patients
      (77.8%) healed. As compared with the CCTD group, patients of the NFTD group had a
      shorter intensive care course (11.95 vs 33.62 days, P= 0.01) and hospital stay
      (39.74 vs 77.54 days, P= 0.02). Although this novel NFTD management did not
      significantly decrease mortality when compared with CCTD, it could gain more
      effective drainage than CCTD and eventually shorten hospital stay.

PMID- 20819103
TI  - Genes for selenium dependent and independent formate dehydrogenase in the gut
      microbial communities of three lower, wood-feeding termites and a wood-feeding
      roach.
AB  - The bacterial Wood-Ljungdahl pathway for CO(2)-reductive acetogenesis is
      important for the nutritional mutualism occurring between wood-feeding insects
      and their hindgut microbiota. A key step in this pathway is the reduction of
      CO(2) to formate, catalysed by the enzyme formate dehydrogenase (FDH). Putative
      selenocysteine- (Sec) and cysteine- (Cys) containing paralogues of hydrogenase
      linked FDH (FDH(H)) have been identified in the termite gut acetogenic
      spirochete, Treponema primitia, but knowledge of their relevance in the termite
      gut environment remains limited. In this study, we designed degenerate PCR
      primers for FDH(H) genes (fdhF) and assessed fdhF diversity in insect gut
      bacterial isolates and the gut microbial communities of termites and cockroaches.
      The insects examined herein represent three wood-feeding termite families,
      Termopsidae, Kalotermitidae and Rhinotermitidae (phylogenetically 'lower' termite
      taxa); the wood-feeding roach family Cryptocercidae (the sister taxon to
      termites); and the omnivorous roach family Blattidae. Sec and Cys FDH(H) variants
      were identified in every wood-feeding insect but not the omnivorous roach. Of 68
      novel alleles obtained from inventories, 66 affiliated phylogenetically with
      enzymes from T. primitia. These formed two subclades (37 and 29 phylotypes)
      almost completely comprised of Sec-containing and Cys-containing enzymes
      respectively. A gut cDNA inventory showed transcription of both variants in the
      termite Zootermopsis nevadensis (family Termopsidae). The gene patterns suggest
      that FDH(H) enzymes are important for the CO(2)-reductive metabolism of
      uncultured acetogenic treponemes and imply that the availability of selenium, a
      trace element, shaped microbial gene content in the last common ancestor of
      dictyopteran, wood-feeding insects, and continues to shape it to this day.

PMID- 20819104
TI  - Metapopulation structure of Vibrionaceae among coastal marine invertebrates.
AB  - Although animal-associated microbial communities (microbiomes) are increasingly
      recognized to influence health, the extent to which animals represent highly
      selective habitats for microbes leading to predominance of high host specificity
      remains poorly understood. Here, we show that vibrios, which are well-known
      commensals and opportunistic pathogens of marine animals, overall display little
      host preference, likely because of efficient dispersal-colonization dynamics
      mediated by food items. We isolated 1753 strains from water and animal samples,
      which are linked in a food chain and display different degrees of similarity
      (respiratory and digestive tract of mussels and crabs, live and dead zooplankton,
      and whole water samples). Multilocus sequence data served as input for modelling
      and statistical analysis of spatiotemporal population structure. These data
      showed that the majority of populations occurred broadly within and among hosts,
      with the dominant population being a near perfect generalist with regard to
      seasons, host taxa and body regions. Zooplankton harboured the fewest and most
      specific populations, while crabs and mussels contained the highest diversity
      with little evidence for host preferences. Most mussel- and crab-associated
      populations were detected in water samples at similar frequencies, particularly
      in filter-feeding mussels where populations were also evenly distributed across
      host individuals. The higher variation among individuals observed in crabs and
      zooplankton is consistent with stochastic clonal expansions. These patterns
      suggest that evolution of a high degree of host specificity is surprisingly rare
      even though these animals represent long-lived habitats, and vibrios are
      consistent members of their microbiome. Instead, many of the populations show
      stronger association with planktonic (micro)habitats while the microbiome may be
      a fairly open system for vibrios in which high rates of immigration can outpace
      selection for specialization.

PMID- 20819105
TI  - Risk-adjusted capitation rates for children: how useful are the survey-based
      measures?
AB  - OBJECTIVE: Despite the recognition by some experts that survey measures have the
      potential to improve capitation rates for those with chronic conditions, few
      studies have examined risk-adjustment models for children, and fewer still have
      focused on survey measures. This study evaluates the performance of risk
      adjustment models for children and examines the potential of survey-based
      measures for improving capitation rates for children. DATA SOURCES: The study
      sample includes 8,352 Medicaid children who were followed up for 2 years by the
      Medical Expenditure Panel Survey in 2000-2005. STUDY METHODS: Children's
      information in 1 year was used to predict their expenditures in the next year.
      Five models were estimated, including one each that used demographic
      characteristics, subjectively rated health status, survey measures about children
      with special health care needs (CSHCN), prior year expenditures, and Hierarchical
      Condition Category (HCC), which is a diagnosis-based model. The models were
      tested at the individual level using multiple regression methods and at the group
      level using split-half validation to evaluate their impact on expenditure
      predictions for CSHCN. PRINCIPAL FINDINGS: The CSHCN information explained higher
      proportion of the variance in annual expenditures than the subjectively rated
      health status, but less than HCC measures and prior expenditures. Adding the
      CSHCN information into demographic factors as adjusters would remarkably increase
      capitation rates for CSHCN. CONCLUSIONS: Survey measures, such as the CSHCN
      information, can improve risk-adjustment models, and their inclusion into
      capitation adjustment may help provide appropriate payments to managed-care plans
      serving this vulnerable group of children.

PMID- 20819106
TI  - State regulatory enforcement and nursing home termination from the medicare and
      medicaid programs.
AB  - OBJECTIVES: Nursing homes certified by the Medicare and/or Medicaid program are
      subject to federally mandated and state-enforced quality and safety standards. We
      examined the relationship between state quality enforcement and nursing home
      terminations from the two programs. STUDY DESIGN: Using data from a survey of
      state licensure and certification agencies and other secondary databases, we
      performed bivariate and multivariate analyses on the strength of state quality
      regulation in 2005, and nursing home voluntary terminations (decisions made by
      the facility) or involuntary terminations (imposed by the state) in 2006-2007.
      PRINCIPAL FINDINGS: Involuntary terminations were rarely imposed by state
      regulators, while voluntary terminations were relatively more common (2.16
      percent in 2006-2007) and varied considerably across states. After controlling
      for facility, market, and state covariates, nursing homes in states implementing
      stronger quality enforcement were more likely to voluntarily terminate from the
      Medicare and Medicaid programs (odds ratio = 1.53, p = .018). CONCLUSIONS:
      Although involuntary nursing home terminations occurred rarely in most states,
      nursing homes in states with stronger quality regulations tend to voluntarily
      exit the publicly financed market. Because of the consequences of voluntary
      terminations on patient care and access, state regulators need to consider the
      effects of increased enforcement on both enhanced quality and the costs of
      termination.

PMID- 20819107
TI  - Access to primary and preventive care among foreign-born adults in Canada and the
      United States.
AB  - OBJECTIVE: To conduct cross-country comparisons and assess the effect of foreign
      birth on access to primary and preventive care in Canada and the United States.
      DATA SOURCES: Secondary data from the 2002 to 2003 Joint Canada-United States
      Survey of Health. STUDY DESIGN: Descriptive and comparative analyses were
      conducted, and logistic regression models were used to assess the effect of
      immigrant status and country of residence on access to care. Outcomes included
      measures of health care systems and processes, utilization, and patient
      perceptions. PRINCIPAL FINDINGS: In adjusted analyses, immigrants in Canada fared
      worse than nonimmigrants regarding having timely Pap tests; in the United States,
      immigrants fared worse for having a regular doctor and an annual consultation
      with a health professional. Immigrants in Canada had better access to care than
      immigrants in the United States; most of these differences were explained by
      differences in socioeconomic status and insurance coverage across the two
      countries. However, U.S. immigrants were more likely to have timely Pap tests
      than Canadian immigrants, even after adjusting for potential confounders.
      CONCLUSIONS: In both countries, foreign-born populations had worse access to care
      than their native-born counterparts for some indicators but not others. However,
      few differences in access to care were found when direct cross-country
      comparisons were made between immigrants in Canada versus the United States,
      after accounting for sociodemographic differences.

PMID- 20819108
TI  - The effects of cost sharing on access to care among childless adults.
AB  - OBJECTIVES: To analyze the impact of public health insurance expansions and the
      use of enrollee cost sharing on insurance status and receipt of clinically
      indicated preventive screenings and physician services. DATA SOURCE: This study
      uses Behavioral Risk Factor Surveillance System (BRFSS) data from 1997 to 2007.
      STUDY DESIGN: This study uses multivariate difference-in-difference logistic
      regression modeling of pooled cross-sectional time series data. The effect of the
      expansions on insurance status and access to care is identified by cross-state
      variation in program implementation, as well as cross-state and within-state
      variation in program eligibility criteria over time. PRINCIPAL FINDINGS:
      Childless adult expansions, regardless of cost-sharing levels, reduced
      uninsurance rates and decreased the likelihood that childless adults needed to
      see a physician but did not because of cost. Expansions with traditional public
      insurance cost-sharing requirements increased the use of preventive screenings,
      while expansions with increased cost-sharing requirements did not. CONCLUSIONS:
      Cost-sharing requirements did not have an impact on the ability to see a
      physician when needed, but they played an important role in the utilization of
      preventive services. Expanding public health insurance to low-income, childless
      adults presents a promising policy opportunity, but there are trade-offs between
      the efficiencies obtained through increased cost sharing and the potential
      inefficiencies due to the lower use of preventive services.

PMID- 20819109
TI  - The trade-off between costs and outcomes: the case of acute myocardial
      infarction.
AB  - OBJECTIVE: To investigate and to quantify the relationship between hospital costs
      and health outcomes for patients with acute myocardial infarction (AMI) in
      Veterans Health Administration (VHA) hospitals using individual-level data for
      costs and outcomes. DATA SOURCES: VHA administrative files for the fiscal years
      2000-2006. STUDY DESIGN: Costs were defined as costs incurred during the index
      hospitalization for treatment of AMI. Mortality and readmission, assessed 1 year
      after the index hospitalization, were used as measures of clinical outcome. We
      examined health outcomes as a function of costs and other patient-level and
      hospital-level characteristics using a two-stage Cox proportional hazard model
      that accounted for competing risks within a multilevel framework. To control for
      patient comorbidities, we compiled a comprehensive list of comorbidities that
      have been found in other studies to affect mortality and readmissions. PRINCIPAL
      FINDINGS: We found that costs were negatively associated with mortality and
      readmissions. Every U.S.$100 less spent is associated with a 0.63 percent
      increase in the hazard of dying and a 1.24 percent increase in the hazard to be
      readmitted conditional on not dying. This main finding remained unchanged after a
      number of sensitivity checks. CONCLUSIONS: Our results suggest that there is a
      trade-off between costs and outcomes. The negative association between costs and
      mortality suggests that outcomes should be monitored closely when introducing
      cost-containment programs. Additional studies are needed to examine the cost
      outcome relationship for conditions other than AMI to see whether our results are
      consistent.

PMID- 20819111
TI  - Derivation and validation of a MEDLINE search strategy for research studies that
      use administrative data.
AB  - OBJECTIVE: To derive and validate a search strategy that identifies
      administrative database research (ADR) in the MEDLINE database. DESIGN:
      Analytical survey. METHODS: We downloaded all articles published between January
      1, 2008 and October 7, 2009 in 20 top journals in internal medicine,
      cardiovascular medicine, public health, and health services research. These were
      reviewed to determine whether they were ADR (in which the study cohort, exposure,
      or outcome was defined using electronic data created for or during the processing
      of patients through their health care). We used chi-squared recursive
      partitioning to create a search strategy that maximized sensitivity based on
      publication type, MeSH headings, and text words. MAIN OUTCOME MEASURES:
      Sensitivity and positive predictive value of the search strategy for true ADR in
      three samples: derivation (n=5,513); internal validation (n=2,710); and external
      validation (n=1,500). RESULTS: The prevalence of ADR in the derivation, internal
      validation, and external validation samples was 2.6, 2.9, and 2.2 percent,
      respectively. The sensitivity of our search strategy in these samples was 90.9
      percent (95 percent confidence interval [CI] 85.0-95.1), 88.5 percent (79.2
      94.6), and 100 percent (99.3-100), respectively. The positive predictive value in
      these samples was 10.7 percent (9.0-12.6), 11.5 percent (9.1-14.4), and 3.3
      percent (2.3-4.6), respectively. CONCLUSION: We derived and validated a search
      strategy that is highly sensitive for ADR in MEDLINE.

PMID- 20819110
TI  - The comprehensive care project: measuring physician performance in ambulatory
      practice.
AB  - OBJECTIVE: To investigate the feasibility, reliability, and validity of
      comprehensively assessing physician-level performance in ambulatory practice.
      DATA SOURCES/STUDY SETTING: Ambulatory-based general internists in 13 states
      participated in the assessment. STUDY DESIGN: We assessed physician-level
      performance, adjusted for patient factors, on 46 individual measures, an overall
      composite measure, and composite measures for chronic, acute, and preventive
      care. Between- versus within-physician variation was quantified by intraclass
      correlation coefficients (ICC). External validity was assessed by correlating
      performance on a certification exam. DATA COLLECTION/EXTRACTION METHODS: Medical
      records for 236 physicians were audited for seven chronic and four acute care
      conditions, and six age- and gender-appropriate preventive services. PRINCIPAL
      FINDINGS: Performance on the individual and composite measures varied
      substantially within (range 5-86 percent compliance on 46 measures) and between
      physicians (ICC range 0.12-0.88). Reliabilities for the composite measures were
      robust: 0.88 for chronic care and 0.87 for preventive services. Higher
      certification exam scores were associated with better performance on the overall
      (r = 0.19; p<.01), chronic care (r = 0.14, p = .04), and preventive services
      composites (r = 0.17, p = .01). CONCLUSIONS: Our results suggest that reliable
      and valid comprehensive assessment of the quality of chronic and preventive care
      can be achieved by creating composite measures and by sampling feasible numbers
      of patients for each condition.

PMID- 20819112
TI  - Developmental regulation of glucose transporters GLUT3, GLUT4 and GLUT8 in the
      mouse cerebellar cortex.
AB  - Glucose uptake into the mammalian nervous system is mediated by the family of
      facilitative glucose transporter proteins (GLUT). In this work we investigate how
      the expression of the main neuronal glucose transporters (GLUT3, GLUT4 and GLUT8)
      is modified during cerebellar cortex maturation. Our results reveal that the
      levels of the three transporters increase during the postnatal development of the
      cerebellum. GLUT3 localizes in the growing molecular layer and in the internal
      granule cell layer. However, the external granule cell layer, Purkinje cell
      cytoplasm and cytoplasm of the other cerebellar cells lack GLUT3 expression.
      GLUT4 and GLUT8 have partially overlapping patterns, which are detected in the
      cytoplasm and dendrites of Purkinje cells, and also in the internal granule cell
      layer where GLUT8 displays a more diffuse pattern. The differential localization
      of the transporters suggests that they play different roles in the cerebellum,
      although GLUT4 and GLUT8 could also perform some compensatory or redundant
      functions. In addition, the increase in the levels and the area expressing the
      three transporters suggests that these roles become more important as development
      advances. Interestingly, the external granule cells, which have been shown to
      express the monocarboxylate transporter MCT2, express none of the three main
      neuronal GLUTs. However, when these cells migrate inwardly to differentiate in
      the internal granule cells, they begin to produce GLUT3, GLUT4 and GLUT8,
      suggesting that the maturation of the cerebellar granule cells involves a switch
      in their metabolism in such a way that they start using glucose as they mature.

PMID- 20819113
TI  - An experimentally validated micromechanical model of a rat vertebra under
      compressive loading.
AB  - In recent years, finite element analysis (FEA) has been increasingly applied to
      examine and predict the mechanical behaviour of craniofacial and other bony
      structures. Traditional methods used to determine material properties and
      validate finite element models (FEMs) have met with variable success, and can be
      time-consuming. An implicit assumption underlying many FE studies is that
      relatively high localized stress/strain magnitudes identified in FEMs are likely
      to predict material failure. Here we present a new approach that may offer some
      advantages over previous approaches. Recently developed technology now allows us
      to both image and conduct mechanical tests on samples in situ using a materials
      testing stage (MTS) fitted inside the microCT scanner. Thus, micro-finite element
      models can be created and validated using both quantitative and qualitative
      means. In this study, a rat vertebra was tested under compressive loading until
      failure using an MTS. MicroCT imaging of the vertebra before mechanical testing
      was used to create a high resolution finite element model of the vertebra. Load
      displacement data recorded during the test were used to calculate the effective
      Young's modulus of the bone (found to be 128 MPa). The microCT image of the
      compressed vertebra was used to assess the predictive qualities of the FE model.
      The model showed the highest stress concentrations in the areas that failed
      during the test. Clearly, our analyses do not directly address biomechanics of
      the craniofacial region; however, the methodology adopted here could easily be
      applied to examine the properties and behaviour of specific craniofacial
      structures, or whole craniofacial regions of small vertebrates. Experimentally
      validated micro-FE analyses are a powerful method in the study of materials with
      complex microstructures such as bone.

PMID- 20819116
TI  - Implicit mechanistic role of the collagen, smooth muscle, and elastic tissue
      components in strengthening the air and blood capillaries of the avian lung.
AB  - To identify the forces that may exist in the parabronchus of the avian lung and
      that which may explain the reported strengths of the terminal respiratory units,
      the air capillaries and the blood capillaries, the arrangement of the
      parabronchial collagen fibers (CF) of the lung of the domestic fowl, Gallus
      gallus variant domesticus was investigated by discriminatory staining, selective
      alkali digestion, and vascular casting followed by alkali digestion. On the
      luminal circumference, the atrial and the infundibular CF are directly connected
      to the smooth muscle fibers and the elastic tissue fibers. The CF in this part of
      the parabronchus form the internal column (the axial scaffold), whereas the CF in
      the interparabronchial septa and those associated with the walls of the
      interparabronchial blood vessels form the external, i.e. the peripheral,
      parabronchial CF scaffold. Thin CF penetrate the exchange tissue directly from
      the interparabronchial septa and indirectly by accompanying the
      intraparabronchial blood vessels. Forming a dense network that supports the air
      and blood capillaries, the CF weave through the exchange tissue. The exchange
      tissue, specifically the air and blood capillaries, is effectively suspended
      between CF pillars by an intricate system of thin CF, elastic and smooth muscle
      fibers. The CF course through the basement membranes of the walls of the blood
      and air capillaries. Based on the architecture of the smooth muscle fibers, the
      CF, the elastic muscle fibers, and structures like the interparabronchial septa
      and their associated blood vessels, it is envisaged that dynamic tensional,
      resistive, and compressive forces exist in the parabronchus, forming a tensegrity
      (tension integrity) system that gives the lung rigidity while strengthening the
      air and blood capillaries.

PMID- 20819117
TI  - No-reflow phenomenon following percutaneous coronary intervention for acute
      myocardial infarction: incidence, outcome, and effect of pharmacologic therapy.
AB  - BACKGROUND: No-reflow (NR) phenomenon is a well-known problem, often accompanying
      percutaneous coronary intervention for acute ST elevation myocardial infarction
      (STEMI). There are little data on effects of pharmacologic therapy on the
      resolution, outcome, and long-term natural history of NR. OBJECTIVE:
      Retrospectively assess incidence, management, and prognosis of NR in a tertiary
      referral hospital. METHODS: Study included patients with STEMI, treated with
      percutaneous coronary intervention (PCI). Effect of pharmacologic therapy and
      long-term outcome were assessed. NR was defined by thrombolysis in myocardial
      infarction (TIMI) < 3 or myocardial blush grade (MBG) < 3. RESULTS: Of 347
      identified subjects, NR occurred in 110 (32%) by TIMI and 198 (57%) by MBG.
      Higher incidence was identified in men versus women (34% vs. 25% by TIMI, P =
      0.08; and 60% vs. 48% by MBG, P = 0.04). Pharmacologic therapy was equally
      effective in restoring normal flow, increasing TIMI score from 1.62 +/- 0.07 to
      2.78 +/- 0.06 (P < 0.0001) and MBG score from 0.43 +/- 0.08 to 2.09 +/- 0.11 (P <
      0.0001). Twenty-three percent who did not receive pharmacologic therapy developed
      clinical composite of congestive heart failure, cardiogenic shock, and/or death;
      only 9% of patients who received pharmacologic therapy developed this composite.
      Patients with severe NR despite treatment had poorer prognosis. Sixty-five
      percent of patients who survived and had repeat angiogram about 1.5 years later
      had spontaneous improvement in coronary flow by MBG. CONCLUSION: NR is common in
      STEMI. Treatment with nicardipine, nitroprusside, and verapamil are equally
      effective in improving flow. If not treated, prognosis is poor.

PMID- 20819118
TI  - PHLPP1 splice variants differentially regulate AKT and PKCalpha signaling in
      hippocampal neurons: characterization of PHLPP proteins in the adult hippocampus.
AB  - Pleckstrin homology and leucine rich repeat protein phosphatases (PHLPPs) are a
      novel class of potent protein kinase B (AKT) inhibitors that have been intensely
      investigated in relation to AKT activity in cancer. Currently, our understanding
      of the role of PHLPP1alpha in the central nervous system is limited. In this
      study, we characterized PHLPP protein expression and target kinases in the adult
      hippocampus. We directly verify PHLPP1alpha inhibits AKT in hippocampal neurons
      and demonstrate a novel role for PHLPP1beta/SCOP, to promote AKT activation.
      PHLPP1alpha expression changes dramatically in the hippocampus during
      development, constituting the most abundant PHLPP protein in adult neurons.
      Further, while all PHLPP proteins could be observed in the cytosolic fraction,
      only PHLPP1alpha could be localized to the nucleus. The results provide unique
      evidence for a divergence in the function of PHLPP1alpha and PHLPP1beta/SCOP, and
      suggest that PHLPP1alpha plays a major role in regulating AKT signaling in
      neurons.

PMID- 20819119
TI  - Electrophysiological effects of melatonin on mouse Per1 and non-Per1
      suprachiasmatic nuclei neurones in vitro.
AB  - The master circadian pacemaker in the suprachiasmatic nuclei (SCN) regulates the
      nocturnal secretion of the pineal hormone melatonin. Melatonin, in turn, has
      feedback effects on SCN neuronal activity rhythms via high affinity G protein
      coupled receptors (MT(1) and MT(2) ). However, the precise effects of melatonin
      on the electrical properties of individual SCN neurones are unclear. In the
      present study, we investigated the acute effects of exogenous melatonin on SCN
      neurones using whole-cell patch-clamp recordings in brain slices prepared from
      Per1::d2EGFP-expressing transgenic mice. In current-clamp mode, bath applied
      melatonin, at near-physiological concentrations (1 nM), hyperpolarised the
      majority (63.7%) of SCN neurones tested at all times of the projected light/dark
      cycle. In addition, melatonin depolarised a small proportion of cells (11.0%). No
      differences were observed for the effects of melatonin between Per1::GFP or non
      Per1::GFP SCN neurones. Melatonin-induced effects were blocked by the MT(1)/MT(2)
      antagonist, luzindole (1 MUM) and the proportion of SCN neurones responsive to
      melatonin was greatly reduced in the presence of either tetrodotoxin (200 or 500
      nM) or gabazine (20 MUM). In voltage-clamp recordings, 1 nM melatonin increased
      the frequency of GABA-mediated currents. These findings indicate, for the first
      time, that exogenous melatonin can alter neuronal excitability in the majority of
      SCN neurones, regardless of whether or not they overtly express the core clock
      gene Per1. The results also suggest that melatonin acts mainly by modulating
      inhibitory GABAergic transmission within the SCN. This may explain why exogenous
      application of melatonin has heterogenous effects on individual SCN neurones.

PMID- 20819120
TI  - Effect of short-and long-term gonadectomy on neuroactive steroid levels in the
      central and peripheral nervous system of male and female rats.
AB  - Significant levels of neuroactive steroids are still detected in the nervous
      system of rodents after the removal of peripheral steroidogenic glands. However,
      the influence of the plasma levels of gonadal steroids on the levels of
      neuroactive steroids in the nervous system has not so far been clarified in
      detail. Accordingly, by liquid chromatography tandem mass spectrometry, we have
      analysed the levels of neuroactive steroids in the sciatic nerve, in three
      central nervous system (CNS) regions (i.e. cerebellum, cerebral cortex and spinal
      cord) and in the plasma of male and female animals. The levels present in
      gonadally intact animals were compared with those present in short- and long-term
      gonadectomised animals. We observed that: (i) changes in neuroactive steroid
      levels in the nervous system after gonadectomy do not necessarily reflect the
      changes in plasma levels; (ii) long-term gonadectomy induces changes in the
      levels of neuroactive steroids in the peripheral nervous system (PNS) and the CNS
      that, in some cases, are different to those induced by short-term gonadectomy;
      (iii) the effect of gonadectomy on neuroactive steroid levels is different
      between the PNS and the CNS and within different CNS regions; and (iv) the
      effects of gonadectomy on neuroactive steroid levels in the nervous system show
      sex differences. Altogether, these observations indicate that the nervous system
      adapts its local levels of neuroactive steroids in response to changes in gonadal
      hormones with sex and regional specificity and depending on the duration of the
      peripheral modifications.

PMID- 20819121
TI  - D-aspartate oxidase localisation in pituitary and pineal glands of the female
      pig.
AB  - Recent evidence has shown that D-aspartate modulates hormone secretion in the
      vertebral neuroendocrine system. Because only D-aspartate oxidase (DDO) can
      degrade D-aspartate, we determined DDO localisation in the pituitary and pineal
      glands to elucidate the control mechanisms of local D-aspartate concentration.
      Brain tissues and pituitary and pineal glands of the female pigs contained a
      similar DDO activity of 0.38-0.66 U/g protein. However, approximately ten-fold
      higher concentrations of D-aspartate (0.27-0.35 MUmol/g protein) were found in
      both glands. To determine the distribution of immunoreactive DDO, we made a
      rabbit polyclonal antibody specific to porcine DDO using a recombinant porcine
      enzyme. DDO immunoreactivity was found in the cytoplasm of a subgroup of cells in
      the anterior and intermediate lobes, in a part of nerve processes and terminals
      in the posterior lobe, and in the cytoplasm of a small group of pinealocytes. We
      used dual-label immunocytochemistry to determine which pituitary hormones
      colocalise with DDO, and whether DDO and D-aspartate immunoreactivity is
      reciprocal. In the pituitary gland, almost all proopiomelanocortin-positive cells
      colocalised DDO, whereas only growth hormone-positive cells colocalised D
      aspartate. D-aspartate immunoreactivity was not detected where DDO
      immunoreactivity was found. The present study suggests that DDO plays important
      roles to prevent undesirable off-target action of D-aspartate by strictly
      controlling local D-aspartate concentration in the pituitary and pineal glands.

PMID- 20819122
TI  - Resetting the dynamic range of hypothalamic-pituitary-adrenal axis stress
      responses through pregnancy.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis plays a key role in the
      neuroendocrine response to stress. Dynamic changes in HPA axis regulation and
      hence HPA responsivity occur over the lifetime of an animal. This article focuses
      on two extremes of the spectrum. The first occurs naturally during pregnancy when
      stress responses are dampened. The second, at the opposite end of the scale,
      occurs in offspring of mothers who were exposed to stress during pregnancy and
      display exaggerated HPA axis stress responses. Reduced glucocorticoid output in
      response to stress in pregnancy may have important consequences for conserving
      energy supply to the foetus(es), in modulating immune system adaptations and in
      protecting against adverse foetal programming by glucocorticoids. Understanding
      the mechanisms underpinning this adaptation in pregnancy may provide insights for
      manipulating HPA axis responsiveness in later life, particularly in the context
      of resetting HPA axis hyperactivity associated with prenatal stress exposure,
      which may underlie several major pathologies, including cardiovascular disease,
      diabetes mellitus type 2, obesity, cognitive decline and mood disorders.

PMID- 20819123
TI  - Oral cancer in Myanmar: a preliminary survey based on hospital-based cancer
      registries.
AB  - The occurrence of oral cancer is not clearly known in Myanmar, where betel quid
      chewing habits are widely spread. Since betel quid chewing has been considered to
      be one of the important causative factors for oral cancer, the circumstantial
      situation for oral cancer should be investigated in this country. We surveyed
      oral cancer cases as well as whole body cancers from two cancer registries from
      Yangon and Mandalay cities, both of which have representative referral hospitals
      in Myanmar, and we showed that oral cancer stood at the 6th position in males and
      10th in females, contributing to 3.5% of whole body cancers. There was a male
      predominance with a ratio of 2.1:1. Their most frequent site was the tongue,
      followed by the palate, which was different from that in other countries with
      betel quid chewing habits. About 90% of male and 44% of female patients had
      habitual backgrounds of chewing and smoking for more than 15 years. The results
      revealed for the first time reliable oral cancer frequencies in Myanmar,
      suggesting that longstanding chewing and smoking habits are etiological
      backgrounds for oral cancer patients.

PMID- 20819124
TI  - EGF/TGFbeta1 co-stimulation of oral squamous cell carcinoma cells causes an
      epithelial-mesenchymal transition cell phenotype expressing laminin 332.
AB  - Epithelial-mesenchymal transition (EMT) is suggested to be crucial for the
      development of an invasive and metastatic carcinoma cell phenotype. Therefore,
      the definition of this phenotype is of great clinical interest. We recently
      evidenced vimentin positive cells in oral squamous cell carcinoma (OSCC) invasive
      front expressing laminin gamma2 chain mRNA implicating an EMT origin of these
      cells. To further elucidate the nature of these cells, we have investigated the
      relation between EMT criteria and laminin-332 expression in a cell culture model
      of transforming growth factor beta-1 (TGFbeta1)/epithelial growth factor (EGF)
      long time co-stimulation. We demonstrate that in contrast to TGFbeta1 or EGF
      alone, co-stimulation induces phenotype transition in OSCC cells which fulfils
      the criteria of EMT in terms of vimentin up-regulation and E-cadherin down
      regulation on protein level as well as cell scattering. Furthermore, cells
      displayed a strongly enhanced invasiveness and adhesion to type I-IV collagens.
      Phenotype transition is accompanied by an enhanced expression of laminin-332,
      especially of its gamma2 chain. We further analyse the expression of
      extracellular matrix related genes by RT-PCR profiling. With respect to strongly
      enhanced proteins, data confirm the EMT phenotype of co-stimulated OSCC cells and
      expression of laminin-332. Furthermore, alpha catenin, collagen type 16, the
      integrin alpha7 and beta1 chains, and MMP11 are suggested as candidates with
      potential role in EMT in OSCC. In summary we are able to show that EMT in OSCC is
      mediated by multiple growth factors and is accompanied by laminin gamma2 chain up
      regulation evidencing the existence of an intermediate Vim(+) /Ln332(+) EMT
      phenotype as seen in situ.

PMID- 20819125
TI  - Association between condylar morphology and changes in bony microstructure and
      sub-synovial inflammation in experimental temporomandibular joint arthritis.
AB  - BACKGROUND: In juvenile idiopathic arthritis involvement of the temporomandibular
      joints (TMJs) is often associated with mandibular growth deviations. The relation
      between the growth deviations and severity of the inflammation, condylar shape,
      the micro-architecture, and the quality of the bone has not previously been
      investigated. This paper studies the effect on the bony structures in mandibular
      condylar development in rabbits with antigen-induced arthritis. METHODS: Included
      were 42 juvenile rabbits with ovalbumin-induced arthritis of the TMJs treated
      with intraarticular saline, intraarticular etanercept or subcutaneous etanercept.
      A TMJ from each animal was scanned using micro-computed tomography and structural
      parameters were calculated. Three-dimensional reconstructions of the mandibular
      condyle were scored blindly as normal or abnormal. TMJs were stratified for
      condylar morphology and were evaluated against data on trabecular structural
      parameters, inflammation, degree of mineralization, overall mandibular growth,
      and mineral apposition rate. RESULTS: Abnormal morphology were seen in 15/32
      animals available for data analysis. Erosions were an uncommon finding. Abnormal
      morphology was strongly related to the degree of inflammation. The trabecular
      separation was larger in group with abnormal morphology than in the group with
      normal morphology. Abnormal condylar morphology was not associated with overall
      mandibular growth. No differences were observed in mineral apposition rate. No
      differences in structural parameters were seen according to treatment modality.
      CONCLUSION: We showed that severe inflammation in the TMJs during mandibular
      development was associated with morphological changes in the mandibular condyle.
      These changes were predominantly seen at the macro-morphological level and only
      very few differences were structural.

PMID- 20819126
TI  - Psychological stress has no association with salivary levels of beta-defensin 2
      and beta-defensin 3.
AB  - BACKGROUND: Recent studies suggest that stress can predispose an individual to
      the development of periodontal disease, but the exact biological mechanism is
      unknown. Considering that psychological stress can down-regulate the production
      of beta-defensins (antimicrobial peptides produced in the oral cavity), the aim
      of the present study was to evaluate the association between stress and salivary
      levels of beta-defensin 2 (HBD-2) and beta-defensin 3 (HBD-3). METHODS: For this
      purpose, seventy five volunteers, classified as periodontally healthy, were
      submitted to a psychological evaluation using a validated questionnaire
      (Questionnaire of Lipp-ISS). Following analysis of the questionnaires, the
      subjects were divided in two groups (Group A: Absence of stress and Group B:
      Presence of stress). Unstimulated saliva samples were collected and the
      concentration of total protein was determined using the BCA method, and the
      concentrations of HBD-2 and HBD-3 were determined by ELISA. RESULTS: The levels
      of total protein did not show a statistically significant difference between the
      groups. Analyses of HBD-2 and HBD-3 concentrations indicate that the stress
      condition was not associated with the levels of either peptide in saliva
      (P=0.3664 for HBD-2 and P=0.3608 for HBD-3). CONCLUSION: In periodontally healthy
      subjects, HBD-2 and HBD-3 levels are not influenced by stress.

PMID- 20819127
TI  - Fibro-osseous lesions of the jaws: an analysis of 122 cases in Thailand.
AB  - BACKGROUND: There are no previously published reports on fibro-osseous jaw
      lesions in Thailand. The aims of this study were to determine the relative
      frequencies and the clinicopathologic features of these lesions in Thailand, and
      to compare these data with information available in the literature. METHODS: A
      total of 122 cases of fibro-osseous lesions of the jaws, out of a total of 4808
      biopsy specimens, were collected from the files of the Department of Oral
      Pathology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand, during a
      34-year period from 1973 to 2006. Clinical data and histopathologic diagnoses
      were reviewed and analyzed. RESULTS: The most common was ossifying fibroma
      (50.8%), followed by fibrous dysplasia (42.6%). Ossifying fibroma most frequently
      occurred in the third and fourth decades of life (61.3%) and mostly involved the
      posterior region of the mandible (41.9%). Fibrous dysplasia was mostly seen in
      the second decade of life (40.4%). The maxilla was involved far more often than
      the mandible (53.8% and 6.2%, respectively), most common in the posterior region
      of the maxilla (28.8%). Both lesions presented as painless swellings (62.9% and
      90.4%, respectively). Radiographically, ossifying fibroma mostly was mixed
      radiolucent-radiopacity (45.2%). Fibrous dysplasia mostly appeared as a
      radiopaque lesion (34.6%). CONCLUSIONS: The relative frequency of osseous
      dysplasia is underestimated because most lesions are not treated and the patients
      are kept under long-term follow-up without biopsy. The clinicopathologic features
      of ossifying fibroma and fibrous dysplasia in Thailand are identical to those in
      the literature.

PMID- 20819128
TI  - Activation of Notch signaling in human tongue carcinoma.
AB  - BACKGROUND: Involvement of Notch signaling in several tumors is well known, but
      its role in tongue squamous cell carcinoma remains poorly characterized. The
      purpose of this study was to evaluate the roles of Notch signaling in the
      oncogenesis of tongue carcinoma. MATERIALS AND METHODS: Tumor specimens and
      adjacent non-neoplastic tongue tissues from 74 patients with tongue carcinoma and
      human tongue carcinoma cell line Tca8113 were examined using immunohistochemistry
      and RT-PCR to determine the expressions of Notch1, Notch3, Jagged1, and Jagged2.
      RESULTS: The mRNA expressions of Notch1, Notch3, Jagged1, and Jagged2 were
      detected in Tca8113, tongue carcinoma, and adjacent non-neoplastic tongue
      tissues. The expression levels of mRNAs in tongue carcinoma were higher than
      those in adjacent non-neoplastic tongue tissues (P < 0.05). Immunohistochemical
      examination showed that the Notch signal molecules were expressed in Tca8113,
      tongue carcinoma, and adjacent non-neoplastic tongue tissues. The expression
      rates of Notch1 and Notch3 protein in tongue carcinoma were higher than those in
      adjacent non-neoplastic tongue tissues (chi2 = 6.10, P = 0.013; chi2 = 3.94, P =
      0.047). Notch1 and jagged1 were significantly more highly expressed in lymph node
      metastasis-positive tongue carcinoma (chi2 = 6.108, P = 0.013; chi2 = 7.354, P =
      0.025). In addition, expressions of Notch3 and Jagged2 were highly correlated in
      tongue carcinoma tissues (chi2 = 42.130, P < 0.001). CONCLUSIONS: Expressions of
      Notch receptors and ligands in tongue carcinoma and adjacent non-neoplastic
      tongue tissues suggest that Notch signaling may control cell differentiation and
      proliferation of carcinoma cells. The disorder of Notch signaling may be a
      mechanism of the tongue carcinoma development.

PMID- 20819129
TI  - Toll-like receptor 5 activation promotes migration and invasion of salivary gland
      adenocarcinoma.
AB  - BACKGROUND: Toll-like receptor (TLR) signaling has been found to be closely
      associated with tumor development. The aim of this study was to examine whether
      activation of TLRs promote migration and invasion of salivary gland
      adenocarcinoma. MATERIALS AND METHODS: TLR expression in SGT and HSG cells was
      examined by RT-PCR. Wound scratch and chemotaxis cell migration assay were
      performed. Invasiveness was determined by Matrigel invasion assay. RESULTS: All
      the tested TLRs including TLR1, TLR2, TLR4, and TLR5 and myeloid differentiation
      factor-2 (MD-2) were expressed on SGT and HSG cells. Treatment of flagellin, but
      not Pam(3) CSK(4) and LPS, led to the production of IL-6 and IL-8, suggesting
      TLR5 is functional in both cells. Stimulation by flagellin also accelerated wound
      closure of SGT and HSG cells in a dose-dependent manner. In addition, flagellin
      promoted migration and invasion ability of SGT cells. Blocking of TLR5 using
      antibody restored the promoting effect of flagellin on migration and invasion of
      SGT cells. CONCLUSION: These findings suggest that TLR5 activation by flagellin
      can promote migration and invasion of salivary gland adenocarcinoma.

PMID- 20819130
TI  - Pathophysiology of oral cancer in experimental animal models: a review with focus
      on the role of sympathetic nerves.
AB  - Global increase in incidence and mortality as well as poor prognosis of oral
      cancer (OC) has intensified efforts towards early detection and prevention of
      this disfiguring disease. Several studies have been conducted using experimental
      animal models to understand the pathophysiology and molecular events involved in
      OC. Lack of identification of specific biomarkers during the multifaceted steps
      of oral carcinogenesis has hindered its diagnosis and treatment. Solid stress
      generated by growing tumors as well as abnormalities in tumor vasculature lead to
      increased interstitial fluid pressure, which could obstruct therapeutic drug
      delivery to tumors. Furthermore, the sympathetic nervous system is known to
      affect angiogenesis, vessel permeability, immune responses and carcinogenesis.
      Recent findings indicate that, in addition to angiogenic and lymphangiogenic
      factors, tumor cells release neurotrophic factors that initiate innervation.
      Interactions between cytokines and sympathetic neurotransmitters, and their
      respective receptors expressed by the nerve, immune and tumor cells appear to
      influence tumor growth. Thus, understanding the complex signaling processes and
      interrelationships between vascular, nervous and immune systems during oral
      carcinogenesis may prove vital for successful prevention and treatment of OC.
      This review aims at outlining the available knowledge on pathophysiology of OC in
      experimental animal models including evidence from our own findings.

PMID- 20819131
TI  - An experimental study of bisphosphonate-induced jaws osteonecrosis in Sprague
      Dawley rats.
AB  - OBJECTIVE: Patients undergoing treatment with bisphosphonates may develop jaw
      lesions consisting mainly of bone necrosis. The present study describes a model
      of maxillary osteonecrosis in Sprague-Dawley rats, applying bisphosphonates and
      examines the changes occurring after tooth extraction. MATERIAL AND METHODS: A
      total 200 animals were included in a randomized prospective study involving the
      following groups: group I (control, 20 rats without drug treatment), group II (60
      animals administered dexamethasone 1 mg/kg/day for 7, 14 and 21 days, in
      subgroups of 20 animals each), group III (60 animals administered pamidronate
      daily at a dose of 3 mg/kg) and group IV (60 animals administered pamidronate and
      dexamethasone). In all groups, molar extraction was carried out on the right
      upper maxillary or mandibular side 8, 15 and 22 days after the start of dosing.
      The rats were killed 14 and 28 days after extraction in all groups. RESULTS: A
      total of 18 cases of osteonecrosis were recorded in the group administered
      pamidronate and dexamethasone. Osteonecrosis affected the upper maxilla in 10
      cases and the mandible in eight cases, and was circumscribed to the extraction
      zone in all cases. Osteonecrosis was not seen in any of the other groups.
      CONCLUSIONS: The administration of pamidronate and dexamethasone in rats
      subjected to molar extraction increases the risk of osteonecrosis.

PMID- 20819132
TI  - Production of IL-10 and IL-12 by antigen-presenting cells in periapical lesions.
AB  - BACKGROUND: Interferon-gamma (IFN-gamma) plays an important role in the
      pathogenesis of periapical lesions. Its expression is up-regulated by interleukin
      (IL)-12) and down-regulated by IL-10. The aim of this work was to study the
      cellular source of these cytokines and their mutual interactions in human
      periapical lesions. METHODS: Mononuclear cells, macrophages and dendritic cells
      were isolated from periapical lesions using plastic adherence and osmotic
      gradients. Cytokines were measured in culture supernatants by a microbeads
      fluorescence assay. Phenotypic characteristics of cells were studied by
      immunocytochemistry, whereas allostimulatory activity of antigen-presenting cells
      was tested using a mixed leukocyte reaction. RESULTS: We observed the positive
      correlations between the levels of IL-12 and IFN-gamma as well as IL-12 and IL-10
      in cultures of mononuclear cells. As IL-10 and IL-12 are produced by dendritic
      cells and activated macrophages, we examined their contribution to the production
      of these cytokines. Macrophages, CD14(+) adherent cells, produced high levels of
      IL-10 and very low levels of IL-12. In contrast, non-adherent, strongly HLA-DR(+)
      dendritic cells, potent stimulators of the alloreactive T-cell response, produced
      low levels of IL-10 and moderate levels of IL-12. Dendritic cells stimulated the
      production of IFN-gamma by allogeneic CD4(+) T cells. In contrast, the level of
      IFN-gamma was significantly decreased and the production of IL-10 was enhanced by
      addition of macrophages to the culture system. CONCLUSION: Our results suggest
      that a fine balance between the production of IL-10 and IL-12 by different
      antigen-presenting cells, through IFN-gamma, may control the course of chronic
      inflammation in periapical lesions.

PMID- 20819133
TI  - Scandinavian Fellowship for Oral Pathology and Oral Medicine: statement on oral
      pathology and oral medicine in the European Dental Curriculum.
AB  - BACKGROUND: For many years, dentists have migrated between the Scandinavian
      countries without an intentionally harmonized dental education. The free movement
      of the workforce in the European Union has clarified that a certain degree of
      standardization or harmonization of the European higher education acts, including
      the dental education, is required. As a result of the Bologna process, the
      Association for Dental Education in Europe and the thematic network DentEd have
      generated guidelines in the document 'Profile and Competences for the European
      Dentist' (PCD). This document is meant to act as the leading source in revisions
      of dental curricula throughout Europe converging towards a European Dental
      Curriculum. In order to render the best conditions for future curriculum
      revisions providing the best quality dentist we feel obliged to analyse and
      comment the outlines of oral pathology and oral medicine in the PCD. METHODS: The
      representatives agreed upon definitions of oral pathology and oral medicine, and
      competences in oral pathology and oral medicine that a contemporary European
      dentist should master. The competences directly related to oral pathology and
      oral medicine were identified, within the PCD. RESULTS: The subject
      representatives suggested eighteen additions and two rewordings of the PCD, which
      all were substantiated by thorough argumentation. PERSPECTIVES: Hopefully, this
      contribution will find support in future revisions of the PCD in order to secure
      the best quality dental education.

PMID- 20819134
TI  - Stress analysis of an all-ceramic FDP loaded according to different occlusal
      concepts.
AB  - The aim of this study was to investigate the influence of four different occlusal
      concepts on stress distribution in a four-unit fixed dental prosthesis (FDP) made
      of zirconia. A three-dimensional finite element (FE) model was created and four
      model versions with between 15 and 42 contact points were developed. A force of
      300 N was distributed over the chewing surface according to the different
      occlusal concepts and virtually applied perpendicularly to the occlusal plane in
      each version. Then, FE analysis was performed and stress distribution evaluated.
      Generally, highest tensile stresses were located at the point of load application
      within the veneering layer and ranged from 104 to 204 MPa. The highest tensile
      stresses within the framework were located at the basal side of the connectors
      and ranged between 12 and 39 MPa. This study shows that the distribution of
      occlusal contact points significantly influences the stresses induced by occlusal
      forces in four-unit all-ceramic fixed dental prostheses and strongly suggests
      that the number and distribution of occlusal contacts may be important to
      minimise fatigue effects caused by cycling.

PMID- 20819135
TI  - The effect of obturator bulb height on speech in maxillectomy patients.
AB  - The purpose of this study was to compare the speech function of low height bulb
      obturators with that of high height bulb obturators. Thirteen maxillectomy
      patients, who underwent post-operative prosthodontic rehabilitations, were
      included. Two obturators of the same design except for different bulb heights
      were fabricated for each maxillectomy patient. One of the two obturators had high
      bulb design and the other had low bulb design. After one of the obturators was
      used for a period of 3 weeks, the patient's speaking functions were evaluated by
      measuring nasalance scores, formant frequencies, and vowel working space areas.
      The same procedures were repeated with the second obturator following another 3
      week period of usage. In addition, the effect of delivery sequence and anatomic
      conditions related to maxillectomy were analysed. The results demonstrated that
      the nasalance scores with the low bulb obturators were significantly higher than
      those with the high bulb obturators. There were no significant differences in
      formant frequencies based on the bulb height of the obturators. The vowel working
      spaces for the two obturators were similar in shape and there were no significant
      differences between the vowel working space areas created by the two obturators.
      The delivery sequence affected the results. However, there were no significant
      differences related to the other anatomical variables. Although low bulb
      obturators might function similarly with high bulb obturators in terms of the
      articulation of speech, they would exhibit a difficulty in controlling
      hypernasality in maxillectomy patients.

PMID- 20819136
TI  - Attitudes of final-year dental students to bleaching of vital and non-vital teeth
      in Cardiff, Cork, and Malmo.
AB  - The aim of this study was to determine attitudes of final-year dental students in
      Cardiff, Cork and Malmo towards tooth whitening. Following receipt of ethical
      approval, pre-piloted questionnaires were distributed to final-year dental
      students in Cork, Cardiff, and Malmo as close as possible to graduation. The
      questionnaire sought information relating to various opinions and attitudes
      towards the use of bleaching techniques including safety of bleaching, confidence
      in the provision of bleaching, recommendations to patients, teaching received,
      awareness of restrictions on the use of bleaching products and management of
      simulated clinical scenarios. Eighty three per cent (n = 116) of questionnaires
      were returned. Cork dental students had the most didactic teaching (2-h vital, 1
      h non-vital bleaching) compared to Cardiff or Malmo students (0 h each). More
      Cork students regarded bleaching as safe (76%, n = 28) than Cardiff (70%, n = 32)
      or Malmo (36%, n = 12) students. More than 50% of Cork students feel they know
      enough about bleaching to provide it in practice, significantly more than Cardiff
      (< 25%) or Malmo (< 25%) students. The majority of students would provide vital
      bleaching after qualification (100% (n = 37) Cork; 82% (n = 27) Malmo; 76% (n =
      35) Cardiff). In simulated clinical scenarios, more Cork students would propose
      bleaching treatments (89%n = 33) than Malmo (64%n = 21) or Cardiff (48%n= 22)
      students. Variations exist in the attitudes and approaches of three European
      dental schools towards bleaching. Dental students need to be best prepared to
      meet the needs of their future patients.

PMID- 20819137
TI  - Selection of the distraction implant length with improved biomechanical
      properties by three-dimensional finite element analysis.
AB  - In this study, the distraction length of distraction implant was set as input
      variable which ranged from 2 to 10 mm. The effect of distraction length on the
      maximum Von Mises stress in the jaw bones and the implant were evaluated by a
      finite element method. The results showed that under axial load, the maximum
      equivalent stresses in cortical bone, cancellous bone, and distraction screw
      decreased by 5.8%, 8.6%, and 11.0%, respectively, with the changing of
      distraction length, and under buccolingual load those decreased by 0.3%, 18.0%,
      and 13.0%, respectively. The data indicate that cancellous bone is more sensitive
      to distraction length than the cortical bone. Under both loads, the central
      distraction screw was subjected to the stress concentration and more easily
      damaged by buccolingual force than by axial force. Distraction implant with
      distraction length exceeding 8 mm showed relatively better biomechanical
      behaviour.

PMID- 20819138
TI  - Current computational modelling trends in craniomandibular biomechanics and their
      clinical implications.
AB  - Computational models of interactions in the craniomandibular apparatus are used
      with increasing frequency to study biomechanics in normal and abnormal
      masticatory systems. Methods and assumptions in these models can be difficult to
      assess by those unfamiliar with current practices in this field; health
      professionals are often faced with evaluating the appropriateness, validity and
      significance of models which are perhaps more familiar to the engineering
      community. This selective review offers a foundation for assessing the strength
      and implications of a craniomandibular modelling study. It explores different
      models used in general science and engineering and focuses on current best
      practices in biomechanics. The problem of validation is considered at some
      length, because this is not always fully realisable in living subjects. Rigid
      body, finite element and combined approaches are discussed, with examples of
      their application to basic and clinically relevant problems. Some advanced
      software platforms currently available for modelling craniomandibular systems are
      mentioned. Recent studies of the face, masticatory muscles, tongue,
      craniomandibular skeleton, temporomandibular joint, dentition and dental implants
      are reviewed, and the significance of non-linear and non-isotropic material
      properties is emphasised. The unique challenges in clinical application are
      discussed, and the review concludes by posing some questions which one might
      reasonably expect to find answered in plausible modelling studies of the
      masticatory apparatus.

PMID- 20819139
TI  - Effect of simulated masticatory loading on the retention of stud attachments for
      implant overdentures.
AB  - This study assessed the effect of simulated mastication on the retention of two
      stud attachment systems for 2-implants overdentures. Sixteen specimens, each
      simulating an edentulous ridge with implants and an overdenture were divided into
      two groups, according to the attachment system: Group I (Nobel Biocare ball
      socket attachments) and Group II (Locator attachments). Retention forces were
      measured before and after 400,000 simulated masticatory loads in a customised
      device. Data were compared by two-way anova followed by Bonferroni test (alpha =
      0.05). Group I presented significantly lower retention forces (Newtons) than
      Group II at baseline (10.6 +/- 3.6 and 66.4 +/- 16.0, respectively). However,
      differences were not significant after 400,000 loads (7.9 +/- 4.3 and 21.6 +/-
      17.0). The number of cycles did not influence the measurements in Group I,
      whereas a non-linear descending curve was found for Group II. It was concluded
      that simulated mastication resulted in minor changes for the ball attachment
      tested. Nevertheless, it reduced the retention of Locator attachments to 40% of
      the baseline values, what suggests that mastication is a major factor associated
      with maintenance needs for this system.

PMID- 20819140
TI  - Validation of the sexual interest and desire inventory-female in hypoactive
      sexual desire disorder.
AB  - INTRODUCTION: The Sexual Interest and Desire Inventory-Female (SIDI-F) is a 13
      item scale developed as a clinician-administered assessment tool to measure
      hypoactive sexual desire disorder (HSDD) severity in women. AIM: To estimate the
      reliability and validity of the SIDI-F as a measure of HSDD severity. METHODS:
      Women, aged 18-65 years, with primary HSDD, Female Sexual Arousal Disorder
      (FSAD), or no Female Sexual Dysfunction (no FSD) participated in two nontreatment
      studies (in North America and Europe). On days 0 and 28, subjects were assessed
      using the SIDI-F, Female Sexual Function Index (FSFI), Changes in Sexual
      Functioning Questionnaire-Female (CSFQ-F), Locke-Wallace Marital Adjustment Test
      (MAT) and the Female Sexual Distress Scale (FSDS). MAIN OUTCOME MEASURES:
      Discriminant validity, convergent validity, divergent validity, test-retest
      validity, and internal consistency of the SIDI-F. RESULTS: The North American
      study enrolled women with HSDD (N = 113), FSAD (N = 49) and no FSD (N = 61); the
      European study enrolled women with HSDD (N = 130) and no FSD (N = 124). In both
      studies, mean SIDI-F total score for women with HSDD was lower than for those
      with no FSD (P < 0.001, for all) demonstrating discriminant validity. Further,
      mean SIDI-F total score for women with HSDD was lower than for those with FSAD in
      the North American study (P < 0.001). Convergent validity with the FSFI and CSFQ
      F and divergent validity with MAT were demonstrated. Test-retest reliability and
      internal consistency were high. CONCLUSIONS: The SIDI-F is a valid and reliable
      measure of HSDD severity in women.

PMID- 20819141
TI  - The female factor: predicting compliance with a post-prostatectomy erectile
      preservation program.
AB  - INTRODUCTION: Early post-radical prostatectomy (RP) erectile preservation (EP)
      therapy may be critical to preserve erections after surgery. AIM: To assess if
      pre-RP female sexual function predicts of partner compliance with an EP protocol.
      MAIN OUTCOME MEASURES: Compliance, defined as use of localized penile EP therapy
      (intracavernosal injections [ICIs], vacuum erection device [VED], or alprostadil)
      at 3 and 6 months after RP. METHODS: Records of patients enrolled in our EP
      program from April 2007 to June 2008 were reviewed. Before surgery, patients
      completed the Sexual Health Inventory for Men (SHIM) and their female partners
      completed the Female Sexual Function Index (FSFI) questionnaire. Prior to
      surgery, patients were advised to take sildenafil 25 mg every nightly and use a
      250-ug alprostadil suppository three times/week. At 1 month, additional daily use
      of a VED was encouraged. All patients unable to achieve erections sufficient for
      penetration were encouraged to initiate ICI of Trimix (phentolamine, papaverine,
      and PGE1) twice weekly after 3 months following surgery. Data were analyzed using
      binary logistic regression analysis holding all input variables constant.
      RESULTS: Twenty-nine patients had preoperative SHIM>7 and pre-RP partner FSFI
      data available. After a 4-week follow-up, compliance with alprostadil suppository
      declined and both ICI and VED usage increased. At 6 months, six (25.0%) patients
      had return of natural erectile function and 22 (91.7%) were achieving assisted
      erections. Higher preoperative partner FSFI scores were associated with greater
      compliance to the localized penile therapy component of our EP protocol (risk
      ratio 3.8, P=0.05). CONCLUSIONS: Preoperative female sexual function correlated
      with greater partner compliance with the localized component of our EP protocol.
      Consideration of a female partner's preoperative sexual function in predicting
      patient erectile function recovery after RP is warranted. Future studies are
      necessary to determine the clinical significance of this factor.

PMID- 20819142
TI  - Bladder perforation associated with hot tub.
AB  - INTRODUCTION: Bladder perforation is a rare and life-threatening event. Timely
      diagnosis may prevent further injury-related morbidity and mortality. Aim.  To
      present a case of bladder injury associated with masturbation in a hot tub.
      METHODS: This report describes a case of bladder perforation in a 54-year-old
      female who presented to the emergency department 2 days after masturbation with a
      water jet. RESULTS: Following percutaneous drainage and intraoperative closure of
      the bladder, the patient was discharged on postoperative day four and has had no
      sequelae. CONCLUSION: Cross-sectional imaging and cystography can facilitate
      immediate diagnosis and expeditious treatment of bladder injury associated with
      masturbation in a hot tub.

PMID- 20819143
TI  - The attitudes to CPAP treatment inventory: development and initial validation of
      a new tool for measuring attitudes to CPAP treatment.
AB  - Continuous positive airway pressure (CPAP) is the treatment of choice for
      obstructive sleep apnoea syndrome (OSAS), but low adherence rates are common. The
      aim was to develop the attitudes to CPAP treatment inventory (ACTI), and to
      investigate the validity and reliability of the instrument among patients with
      OSAS. ACTI was developed on the basis of: (i) in-depth interviews with 23
      patients; (ii) examination of the scientific literature; and (iii) consensus
      agreement of a multi-professional expert panel. This yielded five different types
      of attitudes to CPAP treatment. A prospective longitudinal design was used. Two
      hundred and eighty-nine patients with OSAS were recruited at three different CPAP
      centres. Data were collected with ACTI and obtained from medical records. The
      homogeneity and internal consistency reliability were satisfactorily reflected by
      the item-total correlations (0.59-0.81) and Cronbach's alpha (0.89),
      respectively. Construct validity was confirmed with factor analysis (principal
      component analysis with orthogonal rotation; PCF). The PCF based on baseline data
      resulted in a one single-factor solution explaining 69% of the total variance. A
      confirmatory factor analysis was performed 2 weeks after CPAP initiation,
      resulting in the same factor solution. No indication of uniform differential item
      functioning was found. The predictive validity was tested with receiver operating
      characteristic analyses, and a cut-off of 10 on the ACTI gave a sensitivity of
      93% and a specificity of 44% for CPAP termination within 6 months. The
      satisfactory measurement properties of this new pragmatic instrument are
      promising and indicate that ACTI can be useful in clinical practice to reliably
      measure attitudes to CPAP treatment.

PMID- 20819144
TI  - The effects of insomnia and internet addiction on depression in Hong Kong Chinese
      adolescents: an exploratory cross-sectional analysis.
AB  - The negative association of insomnia and internet addiction with mental health is
      widely documented in the literature, yet little is known about their inter
      relationships. The primary aim of this study was to examine the inter
      relationships between insomnia, internet addiction and depression. A total of 719
      Chinese adolescents in Hong Kong participated in this school-based cross
      sectional study. Participants completed the Chinese version of the Pittsburgh
      Sleep Quality Index (PSQI), the Chinese Internet Addiction Scale (CIAS), the 12
      item version of General Health Questionnaire (GHQ-12) and questions assessing
      internet use pattern and sociodemographic characteristics. The classification of
      internet addiction and insomnia was based on the CIAS cutoff global score >63 and
      PSQI cutoff global score >5, respectively. Multiple regression analyses tested
      the effects of insomnia and internet addiction on depression. Among students with
      internet addiction (17.2%), 51.7% were also identified as insomniacs. Internet
      addicts scored significantly poorer on all PSQI components, except sleep
      duration, than their non-addicted counterparts. After adjustment for gender and
      internet use time, both internet addiction (beta=0.05; Sobel test Z=6.50,
      P<0.001) and insomnia (beta=0.59; Sobel test Z=4.49, P<0.001) demonstrated a
      significant association with depression. Overall, there is high comorbidity
      between internet addiction and insomnia. Both insomnia and internet addiction
      emerged as significant explanatory factors, but they exerted differential effects
      on depression. Future research should be directed at determining the causal
      relationship between internet addiction and insomnia, and its underlying
      mechanism with depression.

PMID- 20819145
TI  - Comparison of sustained attention assessed by auditory and visual psychomotor
      vigilance tasks prior to and during sleep deprivation.
AB  - To date, no detailed examination of the pattern of change in reaction time
      performance for different sensory modalities has been conducted across the
      circadian cycle during sleep deprivation. Therefore, we compared sustained
      auditory and visual attention performance during 40h of sleep deprivation
      assessing multiple metrics of auditory and visual psychomotor vigilance tasks
      (PVT). Forty healthy participants (14 women) aged 30.8+/-8.6years were studied.
      Subjects were scheduled for an ~8h sleep schedule at home prior to three-six
      laboratory baseline days with an 8 h sleep schedule followed by 40h sleep
      deprivation. Visual and auditory PVTs were 10min in duration, and were
      administered every 2h during sleep deprivation. Data were analysed with mixed
      model anova. Sleep deprivation and circadian phase increased response time,
      lapses, anticipations, standard deviation of response times and time on task
      decrements for visual and auditory PVTs. In general, auditory vigilance was
      faster and less variable than visual vigilance, with larger differences between
      auditory and visual PVT during sleep deprivation versus baseline. Failures to
      respond to stimuli within 10s were four times more likely to occur to visual
      versus auditory stimuli. Our findings highlight that lapses during sleep
      deprivation are more than just long responses due to eye closure or visual
      distraction. Furthermore, our findings imply that the general pattern of change
      in attention during sleep deprivation (e.g. circadian variation, response
      slowing, lapsing and anticipations, time on task decrements and state
      instability) is similar among sensory-motor behavioral response modalities.

PMID- 20819146
TI  - Sleep deprivation suppresses the increase of rapid eye movement density across
      sleep cycles.
AB  - We investigated the association between rapid eye movement (REM) density (REMd)
      and electroencephalogram (EEG) activity during non-rapid eye movement (NREM) and
      REM sleep, within the re-assessment, in a large sample of normal subjects, of the
      reduction of oculomotor activity in REM sleep after total sleep deprivation (SD).
      Coherently with the hypothesis of a role of homeostatic sleep pressure in
      influencing REMd, a negative correlation between changes in REMd and slow-wave
      activity (SWA) was expected. A further aim of the study was to evaluate if the
      decreased REMd after SD affects ultradian changes across sleep periods. Fifty
      normal subjects (29 male and 21 female; mean age=24.3 +/- 2.2 years) were studied
      for four consecutive days and nights. Sleep recordings were scheduled in the
      first (adaptation), second (baseline) and fourth night (recovery). After
      awakening from baseline sleep, a protocol of 40 h SD started at 10:00 hours.
      Polysomnographic measures, REMd and quantitative EEG activity during NREM and REM
      sleep of baseline and recovery nights were compared. We found a clear reduction
      of REMd in the recovery after SD, due to the lack of REMd changes across cycles.
      Oculomotor changes positively correlated with a decreased power in a specific
      range of fast sigma activity (14.75-15.25 Hz) in NREM, but not with SWA. REMd
      changes were also related to EEG power in the 12.75-13.00 Hz range in REM sleep.
      The present results confirm the oculomotor depression after SD, clarifying that
      it is explained by the lack of changes in REMd across sleep cycles. The
      depression of REMd can not simply be related to homeostatic mechanisms, as REMd
      changes were associated with EEG power changes in a specific range of spindle
      frequency activity, but not with SWA.

PMID- 20819147
TI  - Intradermal vs intramuscular vaccine against hepatitis B infection in dialysis
      patients: a meta-analysis of randomized trials.
AB  - Chronic dialysis patients are at risk of contracting hepatitis B virus infection
      and have a diminished immune response to hepatitis B virus vaccine. Recent
      reports support intradermal administration of hepatitis B virus vaccine in
      patients on regular dialysis but the efficacy and safety of this approach remain
      unclear. We conducted a meta-analysis of randomized, controlled clinical trials
      to compare seroprotection achieved by intradermal vs intramuscular hepatitis B
      vaccine, in patients on maintenance dialysis. Meta-analysis of data from 718
      adults (14 trials) on long-term dialysis demonstrated that intramuscular
      hepatitis B vaccination was less likely to achieve seroprotection than
      intradermal vaccination, the pooled odds ratio was 0.454 (95% CI, 0.3; 0.67), P =
      0.001. The test of study heterogeneity was not significant. This difference did
      not persist during follow-up (6-60 months after completing vaccine schedule), the
      pooled odds ratio being 0.718 (95% CI, 0.36; 1.47), NS. Some evidence of
      significant heterogeneity including publication bias was present but stratified
      analysis in various subgroups showed that this issue did not meaningfully change
      our results. Intradermal hepatitis B vaccine was safe and well tolerated. We
      conclude that intradermal hepatitis B vaccine induces a superior response rate
      compared to intramuscular route at completion of vaccine cycle, despite a lower
      vaccine dose. No significant advantage was found over longer follow-up. It
      remains unclear whether the higher seroprotection rate achieved with intradermal
      route translates into a lower frequency of de novo hepatitis B among patients on
      maintenance dialysis.

PMID- 20819148
TI  - The impact of smoking on incident type 2 diabetes in a cohort with hepatitis B
      but not hepatitis C infection.
AB  - Smoking may be a risk factor for diabetes, and it has been suggested that viral
      hepatitis may predispose to diabetes. We studied diabetes and smoking histories
      in people with viral hepatitis. From 1997 to 2004, we studied the risk of
      incident diabetes in a community cohort with hyperendemic HBV and HCV infection
      in southern Taiwan. The cohort involved 3539 people (40-70 years old) without
      diabetes. Four hundred and twenty-three individuals developed diabetes. Those who
      were >=65 years old, frequently consumed alcohol, had a BMI >=25, had <9 years of
      education, were anti-HCV+ or smoked >=1 pack per day were more likely to develop
      diabetes (P < 0.05). A cumulative hazard function test showed that the higher the
      smoking levels, the greater the cumulative incidence rate of diabetes in HBsAg+
      participants only (P = 0.03 by log-rank test). A multiple Cox proportional
      hazards model analysis in different hepatitis statuses showed smoking levels were
      strong predictors of diabetes with a dose-response relationship for type 2
      diabetes in those with HBsAg+ : hazard ratio (HR) = 3.8, (95% CI: 1.2, 12.3) for
      light smokers (<1 pack per day) and HR = 4.4 (95% CI: 1.5, 13.3) for heavy
      smokers (>=1 pack per day). Increasing BMI was a common predictor in all people.
      Smoking is a strong predictor for diabetes with a dose-response relationship in
      HBsAg+ individuals and a mild predictor for seronegative individuals but not
      significant in anti-HCV+ individuals.

PMID- 20819149
TI  - Treatment of chronic hepatitis C in HIV-infected patients with compensated liver
      cirrhosis.
AB  - The greatest benefit of hepatitis C virus (HCV) therapy is seen in cirrhotics
      attaining sustained virological response (SVR). However, concerns about toxicity
      and poorer responses often discourage treatment of cirrhotics. This may be
      particularly relevant in HIV-HCV-coinfected patients, in whom progression of
      liver fibrosis is faster and treatment responses lower. This is a retrospective
      analysis of HIV-HCV-coinfected patients who had received peginterferon-ribavirin
      therapy at our institution. Individuals naive for interferon in whom liver
      fibrosis had been assessed using elastometry within the year before being treated
      were chosen. Response rates and toxicities were compared in cirrhotics (>14.5
      KPa) and noncirrhotics. Patients with previous liver decompensation were
      excluded. Overall, 41 cirrhotics and 190 noncirrhotics entered the study. Groups
      were similar in age, gender, HCV genotypes and baseline serum HCV-RNA. SVR
      occurred at similar rates in cirrhotic and noncirrhotics, either considered by
      intention-to-treat (39%vs 45%; P = 0.4) or as treated (50%vs 52%, P = 0.8). In
      multivariate analysis (odds ratio, 95% CI, P), SVR was associated with HCV
      genotypes 2-3 (5, 2.9-11, <0.01) and lower serum HCV-RNA (2, 1.4-3.03 for every
      log decrease, <0.01) but not with cirrhosis (1.2, 0.4-3.6, 0.6). Treatment
      discontinuations because of adverse events tended to be more common in cirrhotics
      than in noncirrhotics (17%vs 12%; P = 0.2), but only severe thrombocytopenia was
      more frequent in cirrhotics than in non-cirrhotics (20%vs 3% at week 24; P <
      0.01). Response to peginterferon-ribavirin therapy is similar in HIV-HCV
      coinfected patients with and without liver cirrhosis. Therefore, treatment must
      be encouraged in all compensated cirrhotic patients, although closer monitoring
      and management of side effects, mainly thrombocytopenia, may be warranted.

PMID- 20819150
TI  - Elimination of hepatitis B virus surface antigen and appearance of neutralizing
      antibodies in chronically infected patients without viral clearance.
AB  - Seroconversion from hepatitis B surface antigen (HBsAg) to antibodies against
      HBsAg (anti-HBs) usually indicates resolution of hepatitis B virus (HBV)
      infection. Here, two HBV-infected patients with seroconversion to anti-HBs were
      found to be persistently positive for HBeAg and HBV DNA. Immunohistology of liver
      biopsies confirmed the expression of HBV proteins in the liver of one patient.
      The neutralizing ability of anti-HBs in patient sera was demonstrated by blocking
      HBV infection of primary tupaia hepatocytes. Analysis of the HBsAg-encoding
      region of HBV isolates from patients indicated the coexistence of heterogeneous
      HBV genomes in patients. The majority of recombinant variant HBsAg was reactive
      in HBsAg assays and was able to bind to anti-HBs. Circulating immune complexes
      (CIC) of HBsAg in patient sera could be detected by polyethylene glycol
      precipitation and trypsin digestion. Thus, neutralizing anti-HBs may appear in
      chronic HBV carriers for long periods but does not necessarily lead to complete
      viral clearance.

PMID- 20819151
TI  - New piophilid in town: the first Palaearctic record of Piophila megastigmata and
      its coexistence with Piophila casei in central Spain.
AB  - The genus Piophila Fallen (Diptera: Piophilidae) is known from only two species:
      Piophila casei (L.) is a major pest, a cosmopolitan species and is commonly used
      as a forensic indicator, whereas Piophila megastigmata McAlpine has until now
      only been recorded in a natural environment in South Africa. The present work
      reports the first occurrence of P. megastigmata in the Palaearctic region from
      specimens collected by carrion-baited traps throughout different natural habitats
      of central Spain. Furthermore, the species was also collected with P. casei on
      corpses of domestic pigs used in a carrion succession study in a periurban
      habitat in central Spain. Both species occurred on carrion in different seasons,
      but P. megastigmata was more abundant than P. casei in autumn, arriving earlier
      at the carcasses and persisting for a longer period. The contrary pattern was
      observed in spring. The presence of P. megastigmata in different localities in
      central Spain and its coexistence with P. casei in a periurban habitat make it a
      potentially useful new tool for legal medicine in Europe; thus this species must
      be considered in forensic entomology studies.

PMID- 20819152
TI  - Impact of Dermatophagoides pteronyssinus mite body raw material on house dust
      mite allergy diagnosis in a Serbian population.
AB  - House dust mite (HDM) allergy has different clinical and immunological patterns
      in different geographic regions. The impact of raw material of commercial
      Dermatophadoides pteronyssinus (Acari: Pyroglyphidae) mite bodies on the quality
      of allergen extracts for allergy diagnosis in the Serbian population has not been
      previously evaluated. House dust mite bodies obtained from manufacturers in
      Europe, South America and Australia were used in the preparation of allergen
      extracts for in vivo diagnosis and serological analysis in a group of 14 HDM
      allergic adults. In the group of mite-allergic patients, there was no
      statistically significant difference in skin test reactivity (Wilcoxon matched
      pairs test) among the three HDM body extract preparations. In a CAP inhibition
      assay, two extracts (A and C) achieved maximum inhibition of >90%, whereas
      extract B demonstrated a different inhibition slope and lower inhibition
      potential (80%). However, a remarkable difference in immunoglobulin E reactivity
      using Western blot analysis with individual patients' sera was observed in one of
      the preparations (extract B). These findings emphasize the need for the careful
      selection of starting material for the preparation of HDM diagnostic reagents
      intended for use in patients from geographically distinct regions as these
      preparations can have implications on the selection criteria for patient-tailored
      immunotherapy of HDM allergy.

PMID- 20819153
TI  - Efficiency of sulphur in garlic extract and non-sulphur homeopathy in the control
      of the cattle tick Rhipicephalus (Boophilus) microplus.
AB  - The objective of the present work was to evaluate the efficacy of a non-sulphur
      based homeopathic preparation and a sulphur-containing natural product derived
      from Allium sativum (Linnaeus) against infestation by the cattle tick
      Rhipicephalus (Boophilus) microplus (Canestrini) (Acari: Ixodidae). A total of 24
      crossbred calves (7 : 8 Holstein : Zebu), aged 6-8 months and maintained in
      individual stables under tick-free conditions, were divided into three groups.
      Group 1 (control group) received no treatment; Group 2 was treated with 0.01
      g/day of the homeopathic preparation Fator C&MC((r)), and Group 3 was treated
      with 20 g/day of Enxofre-Allium sativum((r)). After adaptation to the diet for 1
      month, each calf was subjected to artificial infestation with 8000 R. (B.)
      microplus larvae (aged 7-14 days) twice per week over a 5-month period. Numbers
      of engorged females were recorded every 14 days and samples of freely released
      engorged females were collected at 14-day intervals commencing 3 months after the
      start of the experiment. The engorged females were weighed, incubated for 15 days
      under biochemical oxygen demand conditions at 27 +/- 1  degrees C and relative
      humidity >85%, and the weights of the egg masses produced were recorded. Other
      biological parameters, including reproduction estimate, reduction in oviposition
      and efficiency of treatment, were determined. A significant reduction in the
      number of engorged females was detected on animals treated with Enxofre-Allium
      sativum((r)) (Group 3) in comparison with the other two groups. The overall
      efficiency of the treatment with the sulphur-containing product was 64%, whereas
      that of the homeopathic preparation was 26%. Under the experimental conditions
      established, Enxofre-Allium sativum((r)) can reduce the intensity of the R. (B.)
      microplus infestation.

PMID- 20819155
TI  - Comprehensive paternity assignment: genotype, spatial location and social status
      in song sparrows, Melospiza Melodia.
AB  - Comprehensive, accurate paternity assignment is critical to answering numerous
      questions in evolutionary ecology. Yet, most studies of species with extra-pair
      paternity (EPP) fail to assign sires to all offspring. Common limitations include
      incomplete and biased sampling of offspring and males, particularly with respect
      to male location and social status, potentially biasing estimated patterns of
      paternity. Studies that achieve comprehensive sampling and paternity assignment
      are therefore required. Accordingly, we genotyped virtually all males and >99% of
      6-day-old offspring over 16 years in a song sparrow (Melospiza melodia)
      population and used three complementary statistical methodologies to attempt
      complete paternity assignment for all 2207 offspring. Assignments were highly
      consistent across maximum likelihood methods that used solely genotype data, and
      heuristic and integrated Bayesian analyses that included data describing
      individual locations. Sires were assigned to >99% of all genotyped offspring with
      >=95% confidence, revealing an EPP rate of c. 28%. Extra-pair sires primarily
      occupied territories neighbouring their extra-pair offspring; spatial location
      was therefore highly informative for paternity assignment. EPP was biased towards
      paired territorial males, although unpaired territorial and floater males sired
      c. 13% of extra-pair offspring. Failing to sample and include unpaired males as
      candidate sires would therefore substantially reduce assignment rates. These
      analyses demonstrate the integration of genetic and ecological information to
      achieve comprehensive paternity assignment and direct biological insight,
      illustrate the potential biases that common forms of incomplete sampling could
      have on estimated patterns of EPP, and provide an essential basis for
      understanding the evolutionary causes and consequences of EPP.

PMID- 20819157
TI  - Spaceflight-related suboptimal conditions can accentuate the altered gravity
      response of Drosophila transcriptome.
AB  - Genome-wide transcriptional profiling shows that reducing gravity levels during
      Drosophila metamorphosis in the International Space Station (ISS) causes
      important alterations in gene expression: a large set of differentially expressed
      genes (DEGs) are observed compared to 1g controls. However, the preparation
      procedures for spaceflight and the nonideal environmental conditions on board the
      ISS subject the organisms to additional environmental stresses that demonstrably
      affect gene expression. Simulated microgravity experiments performed on the
      ground, under ideal conditions for the flies, using the random position machine
      (RPM), show much more subtle effects on gene expression. However, when the ground
      experiments are repeated under conditions designed to reproduce the additional
      environmental stresses imposed by spaceflight procedures, 79% of the DEGs
      detected in the ISS are reproduced by the RPM experiment. Gene ontology analysis
      of them shows they are genes that affect respiratory activity, developmental
      processes and stress-related changes. Here, we analyse the effects of
      microgravity on gene expression in relation to the environmental stresses imposed
      by spaceflight. Analysis using 'gene expression dynamics inspector' (GEDI) self
      organizing maps reveals a subtle response of the transcriptome to microgravity.
      Remarkably, hypergravity simulation induces similar response of the
      transcriptome, but in the opposite direction, i.e. the genes promoted under
      microgravity are usually suppressed under hypergravity. These results suggest
      that the transcriptome is finely tuned to normal gravity and that microgravity,
      together with environmental constraints associated with space experiments, can
      have profound effects on gene expression. 

PMID- 20819158
TI  - The anatomy of a 'suture zone' in Amazonian butterflies: a coalescent-based test
      for vicariant geographic divergence and speciation.
AB  - Attempts by biogeographers to understand biotic diversification in the Amazon
      have often employed contemporary species distribution patterns to support
      particular theories, such as Pleistocene rainforest refugia, rather than to test
      among alternative hypotheses. Suture zones, narrow regions where multiple contact
      zones and hybrid zones between taxa cluster, have been seen as evidence for past
      expansion of whole biotas that have undergone allopatric divergence in vicariant
      refuges. We used coalescent analysis of mutilocus sequence data to examine
      population split times in 22 pairs of geminate taxa in ithomiine and heliconiine
      butterflies. We test a hypothesis of simultaneous divergence across a suture zone
      in NE Peru. Our results reveal a scattered time course of diversification in this
      suture zone, rather than a tight cluster of split times. Additionally, we find
      rapid diversification within some lineages such as Melinaea contrasting with
      older divergence within lineages such as the Oleriina (Hyposcada and Oleria).
      These results strongly reject simple vicariance as a cause of the suture zone. At
      the same time, observed lineage effects are incompatible with a series of
      geographically coincident vicariant events which should affect all lineages
      similarly. Our results suggest that Pleistocene climatic forcing cannot readily
      explain this Peruvian suture zone. Lineage-specific biological traits, such as
      characteristic distances of gene flow or varying rates of parapatric divergence,
      may be of greater importance. 

PMID- 20819159
TI  - Quantifying the lag time to detect barriers in landscape genetics.
AB  - Understanding how spatial genetic patterns respond to landscape change is crucial
      for advancing the emerging field of landscape genetics. We quantified the number
      of generations for new landscape barrier signatures to become detectable and for
      old signatures to disappear after barrier removal. We used spatially explicit,
      individual-based simulations to examine the ability of an individual-based
      statistic [Mantel's r using the proportion of shared alleles' statistic (Dps)]
      and population-based statistic (FST ) to detect barriers. We simulated a range of
      movement strategies including nearest neighbour dispersal, long-distance
      dispersal and panmixia. The lag time for the signal of a new barrier to become
      established is short using Mantel's r (1-15 generations). FST required
      approximately 200 generations to reach 50% of its equilibrium maximum, although
      G'ST performed much like Mantel's r. In strong contrast, FST and Mantel's r
      perform similarly following the removal of a barrier formerly dividing a
      population. Also, given neighbour mating and very short-distance dispersal
      strategies, historical discontinuities from more than 100 generations ago might
      still be detectable with either method. This suggests that historical events and
      landscapes could have long-term effects that confound inferences about the
      impacts of current landscape features on gene flow for species with very little
      long-distance dispersal. Nonetheless, populations of organisms with relatively
      large dispersal distances will lose the signal of a former barrier within less
      than 15 generations, suggesting that individual-based landscape genetic
      approaches can improve our ability to measure effects of existing landscape
      features on genetic structure and connectivity. 

PMID- 20819160
TI  - Multiple ice-age refugia in Pacific cod, Gadus macrocephalus.
AB  - Pleistocene ice-ages greatly influenced the historical abundances of Pacific cod,
      Gadus macrocephalus, in the North Pacific and its marginal seas. We surveyed
      genetic variation at 11 microsatellite loci and mitochondrial (mt) DNA in samples
      from twelve locations from the Sea of Japan to Washington State. Both
      microsatellite (mean H = 0.868) and mtDNA haplotype (mean h = 0.958) diversities
      were large and did not show any geographical trends. Genetic differentiation
      between samples was significantly correlated with geographical distance between
      samples for both microsatellites (FST = 0.028, r(2) = 0.33) and mtDNA (FST =
      0.027, r(2) = 0.18). Both marker classes showed a strong genetic discontinuity
      between northwestern and northeastern Pacific populations that likely represents
      groups previously isolated during glaciations that are now in secondary contact.
      Significant differences appeared between samples from the Sea of Japan and
      Okhotsk Sea that may reflect ice-age isolations in the northwest Pacific. In the
      northeast Pacific, a microsatellite and mtDNA partition was detected between
      coastal and Georgia Basin populations. The presence of two major coastal mtDNA
      lineages on either side of the Pacific Ocean basin implies at least two ice-age
      refugia and separate postglacial population expansions facilitated by different
      glacial histories. Northward expansions into the Gulf of Alaska were possible 14
      15 kyr ago, but deglaciation and colonization of the Georgia Basin probably
      occurred somewhat later. Population expansions were evident in mtDNA mismatch
      distributions and in Bayesian skyline plots of the three major lineages, but the
      start of expansions appeared to pre-date the last glacial maximum.

PMID- 20819161
TI  - Clonal diversity, clonal persistence and rapid taxon replacement in natural
      populations of species and hybrids of the Daphnia longispina complex.
AB  - Hybridization is common among cyclical parthenogens, especially in zooplankton
      species assemblages of the genus Daphnia. To explore hybridization dynamics and
      the extent of clonal diversity in the Daphnia longispina complex, we analysed
      population structure in eight permanent lakes. Based on 15 microsatellite loci,
      three major taxonomic units emerged: two species, D. galeata and D. longispina
      and their F1 hybrids, supported by factorial correspondence analysis and two
      Bayesian methods. At the same time, the detection of backcross classes differed
      between methods. Mean clonal diversity was lowest in the F1 hybrids, as expected
      from the high rate of asexual reproduction. Within taxa, replicated genotypes
      were of clonal origin, but clonal lineages persisted in subsequent years in only
      one of three resampled lakes. In another lake, the taxon composition changed from
      being dominated by hybrids to complete dominance by one parental taxon. Such a
      year-to-year taxon replacement has not been reported for the D. longispina
      complex before. Our data on this hybrid complex illustrate that high-resolution
      genotyping is essential for the understanding of ecological and evolutionary
      outcomes of hybridization in partially clonal taxa. 

PMID- 20819162
TI  - Historical influences dominate the population genetic structure of a sedentary
      marine fish, Atlantic wolffish (Anarhichas lupus), across the North Atlantic
      Ocean.
AB  - Genetic variation was assessed in Atlantic wolffish, Anarhichas lupus, across the
      North Atlantic Ocean using microsatellite and amplified fragment length
      polymorphism (AFLP) markers. Despite unusual life history attributes such as
      large benthic eggs, large larvae, a limited pelagic stage and relatively
      sedentary adults, which suggest potential for strong population structure, range
      wide FST values were comparable to other marine fishes (<=0.035). Nevertheless,
      both significant genetic differentiation among regions and isolation by distance
      were observed, suggesting limited dispersal in this species. AFLP loci, evaluated
      on a subset of samples, revealed slightly higher FST values, but similar patterns
      of differentiation and isolation-by-distance estimates, compared to
      microsatellites. The genetic structure of Atlantic wolffish has likely been
      shaped by its post-glacial history of recolonization, North Atlantic current
      patterns and continuity of habitat on continental shelves. 

PMID- 20819163
TI  - Rapid, pervasive genetic differentiation of urban white-footed mouse (Peromyscus
      leucopus) populations in New York City.
AB  - We investigated genetic diversity and structure of urban white-footed mouse,
      Peromyscus leucopus, populations in New York City (NYC) using variation at 18
      microsatellite loci. White-footed mice are 'urban adapters' that occur at higher
      population densities as habitat fragments are reduced in area but have a limited
      ability to disperse through urbanized areas. We hypothesized that this
      combination of traits has produced substantial genetic structure but minimal loss
      of genetic variation over the last century in NYC. Allelic diversity and
      heterozygosity in 14 NYC populations were high, and nearly all of our NYC study
      sites contained genetically distinct populations of white-footed mice as measured
      by pairwise FST , assignment tests, and Bayesian clustering analyses performed by
      Structure and baps. Analysis of molecular variance revealed that genetic
      differences between populations separated by a few kilometres are more
      significant than differences between prehistorically isolated landmasses (i.e.
      Bronx, Queens, and Manhattan). Allele size permutation tests and lack of
      isolation by distance indicated that mutation and migration are less important
      than drift as explanations for structure in urban, fragmented P. leucopus
      populations. Peromyscus often exhibit little genetic structure over even regional
      scales, prompting us to conclude that urbanization is a particularly potent
      driver of genetic differentiation compared to natural fragmentation. 

PMID- 20819164
TI  - Novel insights into Haemagglutinin Protease (HAP) gene regulation in Vibrio
      cholerae.
AB  - Quorum sensing is the phenomenon, whereby bacteria use signal molecules to
      communicate with each other. For example, to establish a successful infection,
      pathogenic bacteria become virulent only when they reach a certain local
      concentration in their host. Bassler and others have highlighted the surprising
      observation that quorum sensing seems to repress Vibrio cholerae virulence factor
      expression (e.g. cholera toxin), in contrast to what has been observed for
      virulence gene expression in other bacteria. Here, I present a novel insight that
      may clarify the way V. cholerae quorum-sensing signals regulate its genes.
      Chironomids (Diptera; Chironomidae), which occur worldwide and are frequently the
      insect found most abundantly in fresh water bodies, are natural reservoirs of V.
      cholerae. Quorum-sensing signals in V. cholerae up-regulate the production of an
      extracellular enzyme, haemagglutinin protease (HAP), which degrades chironomid
      egg masses and prevents the eggs from hatching. HAP, therefore, is a virulence
      factor against chironomids. Indeed, in a survey carried out over the course of a
      year, V. cholerae and chironomids showed a pattern that mirrored the dynamics of
      predator-prey populations. Globally, the numbers of chironomids are much larger
      than those of humans, so quorum-sensing signals of V. cholerae and HAP gene
      regulation should be understood with regard to their role in chironomids rather
      than humans. Further research is needed to understand the role of cholera toxin
      in the environmental existence of V. cholerae. 

PMID- 20819165
TI  - Patterns of differential introgression in a salamander hybrid zone: inferences
      from genetic data and ecological niche modelling.
AB  - Hybrid zones have yielded considerable insight into many evolutionary processes,
      including speciation and the maintenance of species boundaries. Presented here
      are analyses from a hybrid zone that occurs among three salamanders -Plethodon
      jordani, Plethodon metcalfi and Plethodon teyahalee- from the southern
      Appalachian Mountains. Using a novel statistical approach for analysis of non
      clinal, multispecies hybrid zones, we examined spatial patterns of variation at
      four markers: single-nucleotide polymorphisms (SNPs) located in the mtDNA ND2
      gene and the nuclear DNA ILF3 gene, and the morphological markers of red cheek
      pigmentation and white flecks. Concordance of the ILF3 marker and both
      morphological markers across four transects is observed. In three of the four
      transects, however, the pattern of mtDNA is discordant from all other markers,
      with a higher representation of P. metcalfi mtDNA in the northern and lower
      elevation localities than is expected given the ILF3 marker and morphology. To
      explore whether climate plays a role in the position of the hybrid zone, we
      created ecological niche models for P. jordani and P. metcalfi. Modelling results
      suggest that hybrid zone position is not determined by steep gradients in
      climatic suitability for either species. Instead, the hybrid zone lies in a
      climatically homogenous region that is broadly suitable for both P. jordani and
      P. metcalfi. We discuss various selective (natural selection associated with
      climate) and behavioural processes (sex-biased dispersal, asymmetric reproductive
      isolation) that might explain the discordance in the extent to which mtDNA and
      nuclear DNA and colour-pattern traits have moved across this hybrid zone. 

PMID- 20819166
TI  - Evidence for range stasis during the latter Pleistocene for the Atlantic Coastal
      Plain endemic genus, Pyxidanthera Michaux.
AB  - The general phylogeographical paradigm for eastern North America (ENA) is that
      many plant and animal species retreated into southern refugia during the last
      glacial period, then expanded northward after the last glacial maximum (LGM).
      However, some taxa of the Gulf and Atlantic Coastal Plain (GACP) demonstrate
      complex yet recurrent distributional patterns that cannot be explained by this
      model. For example, eight co-occurring endemic plant taxa with ranges from New
      York to South Carolina exhibit a large disjunction separating northern and
      southern populations by >300 km. Pyxidanthera (Diapensiaceae), a plant genus that
      exhibits this pattern, consists of two taxa recognized as either species or
      varieties. We investigated the taxonomy and phylogeography of Pyxidanthera using
      morphological data, cpDNA sequences, and amplified fragment length polymorphism
      markers. Morphological characters thought to be important in distinguishing
      Pyxidanthera barbulata and P. brevifolia demonstrate substantial overlap with no
      clear discontinuities. Genetic differentiation is minimal and diversity estimates
      for northern and southern populations of Pxyidanthera are similar, with no
      decrease in rare alleles in northern populations. In addition, the northern
      populations harbour several unique cpDNA haplotypes. Pyxidanthera appears to
      consist of one morphologically variable species that persisted in or near its
      present range at least through the latter Pleistocene, while the vicariance of
      the northern and southern populations may be comparatively recent. This work
      demonstrates that the refugial paradigm is not always appropriate and GACP
      endemic plants, in particular, may exhibit phylogeographical patterns
      qualitatively different from those of other ENA plant species.

PMID- 20819168
TI  - Smad ubiquitination regulatory factor-2 in progressive supranuclear palsy.
AB  - AIMS: Smad ubiquitination regulatory factor-2 (Smurf2) is an E3 ligase that
      belongs to the HECT domain ubiquitin ligase family. Smurf2 can interact with Smad
      proteins and promote their ubiquitin-dependent degradation, thereby controlling
      the cellular levels of these signalling mediators. Phosphorylated Smad2/3
      (pSmad2/3) was recently identified in phosphorylated tau (phospho-tau) inclusions
      in patients with progressive supranuclear palsy (PSP). As Smurf2 is the E3 ligase
      of pSmad2, we aimed at investigating the relationship among Smurf2, pSmad2/3 and
      phospho-tau in this study. METHODS: The brains of six PSP and three control
      patients without neurological disorder were investigated by immunohistochemical
      analysis. RESULTS: In the control subjects, Smurf2 immunoreactivity was not
      demonstrable in the neurones and glial cells, and that for pSmad2/3 was observed
      exclusively in neuronal and glial nuclei. In PSP patients, the pathognomonic
      neuronal and glial phospho-tau inclusions were immunopositive for both Smurf2 and
      pSmad2/3. The intensity of pSmad2/3 immunosignals of neuronal and glial nuclei
      containing phospho-tau inclusions was less than that for the cells without the
      inclusions. Triple immunofluorescence staining for Smurf2, pSmad2/3 and phospho
      tau revealed co-localization of these proteins within the neuronal and glial
      inclusions; and in some globose neurofibrillary tangles, the Smurf2
      immunoreactivity appeared more centrally distributed than that of pSmad2/3 and
      phospho-tau. CONCLUSIONS: This is the first demonstration of the presence of
      Smurf2 immunoreactivity in the phospho-tau inclusions in PSP. These findings
      suggest that Smurf2 plays a significant role in the pathomechanism of PSP by
      causing abnormal redistribution of neuronal nuclear pSmad2/3 to the cytoplasm.

PMID- 20819167
TI  - TDP-43 proteinopathy in familial motor neurone disease with TARDBP A315T
      mutation: a case report.

PMID- 20819169
TI  - A novel brain metastases model developed in immunodeficient rats closely mimics
      the growth of metastatic brain tumours in patients.
AB  - AIMS: brain metastasis is a common cause of mortality in cancer patients, and
      associated with poor prognosis. Our objective was to develop a clinically
      relevant animal model by transplanting human biopsy spheroids derived from
      metastatic lesions into brains of immunodeficient rats. METHODS: nine different
      patient brain metastases from four different primary cancers were implanted into
      brains of immunodeficient rats. The xenografts were compared with patient tumours
      by magnetic resonance imaging, histochemistry, immunohistochemistry and DNA copy
      number analysis. RESULTS: after transplantation, tumour growth was achieved in
      seven out of nine human brain metastases. Spheroids derived from four of the
      metastases initiated in the rat brains were further serially transplanted into
      new animals and a 100% tumour take was observed during second passage. Three of
      the biopsies were implanted subcutaneously, where no tumour take was observed.
      The animal brain metastases exhibited similar radiological features as observed
      clinically. Histological comparisons between the primary tumours from the
      patients, the patient brain metastases and the derived xenografts showed striking
      similarities in histology and growth patterns. Also, immunohistochemistry showed
      a strong marker expression similarity between the patient tumours and the
      corresponding xenografts. DNA copy number analysis between the brain metastases,
      and the corresponding xenografts revealed strong similarities in gains and losses
      of chromosomal content. CONCLUSION: we have developed a representative in vivo
      model for studying the growth of human metastatic brain cancers. The model
      described represents an important tool to assess responses to new treatment
      modalities and for studying mechanisms behind metastatic growth in the central
      nervous system.

PMID- 20819170
TI  - Neonatal rat model of intraventricular haemorrhage and post-haemorrhagic
      ventricular dilatation with long-term survival into adulthood.
AB  - AIMS: post-haemorrhagic ventricular dilatation (PHVD) is a significant problem in
      neonatal care, with sequelae extending beyond childhood. Its management is
      important in determining outcome. Although rodent hydrocephalus models have been
      developed, PHVD, as a specific entity with a distinct pathophysiology, has not
      been studied in a small animal model surviving to adulthood. Our objective is to
      evaluate survival, to adulthood, in our immature (7-day-old, P7) neonatal rat
      model, and to analyse early motor reflexes and fine motor and cognitive function,
      and neuropathology, at 8-12 weeks. METHODS: sixty-six rats underwent sequential
      bilateral stereotactic intraventricular haemorrhage (IVH); 36 more acted as
      controls. Staircase and radial maze evaluations were carried out at 7-11 weeks;
      animals were sacrificed at 12 weeks. Post mortem ventricular size and corpus
      callosum thickness were determined. RESULTS: seventy-six per cent of IVH animals
      developed PHVD; median (interquartile range) composite ventricular area was 3.46
      mm(2) (2.32-5.24). Sixteen (24%) animals demonstrated severe ventricular
      dilatation (area > 5 mm(2) ). IVH animals failed to improve on the negative
      geotaxis test at 2 weeks. The staircase test did not identify any significant
      difference. On the radial maze, animals with severe PHVD made more reference
      errors. Histopathology confirmed PHVD, ependymal disruption and periventricular
      white matter injury. Median anterior corpus callosum thickness was significantly
      lower in IVH animals (0.35 mm) than in those not undergoing IVH (0.43 mm).
      CONCLUSION: our P7 neonatal rat IVH model is suitable for long-term survival and
      replicates many of the morphological and some of the behavioural features seen in
      human PHVD.

PMID- 20819171
TI  - Combined NgR vaccination and neural stem cell transplantation promote functional
      recovery after spinal cord injury in adult rats.
AB  - AIMS: after spinal cord injury (SCI), there are many adverse factors at the
      lesion site such as glial scar, myelin-derived inhibitors, cell loss and
      deficiency of neurotrophins that impair axonal regeneration. Therefore,
      combination therapeutic strategies might be more effective than a single strategy
      for promoting functional recovery after SCI. In the present study, we
      investigated whether a Nogo66 receptor (NgR) vaccine, combined with neural stem
      cell (NSC) transplantation, could promote better functional recovery than when
      NgR vaccine or NSCs were used alone. METHODS: adult rats were immunized with NgR
      vaccine at 1 week after a contusive SCI at the thoracic level, and the NSCs,
      obtained from green fluorescent protein transgenic rats, were transplanted into
      the injury site at 8 weeks post injury. The functional recovery of the animals
      under various treatments was evaluated by three independent behavioural tests,
      that is, Basso, Beattie and Bresnahan locomotor rating scale, footprint analysis
      and grid walking. RESULTS: the combined therapy with NgR vaccination and NSC
      transplantation protected more ventral horn motor neurones in the injured spinal
      cord and greater functional recovery than when they were used alone. Furthermore,
      NgR vaccination promoted migration of engrafted NSCs along the rostral-caudal
      axis of the injured spinal cords, and induced their differentiation into neurones
      and oligodendrocytes in vivo. CONCLUSIONS: the combination therapy of NgR vaccine
      and NSC transplantation exhibited significant advantages over any single therapy
      alone in this study. It may represent a potential new therapy for SCI.

PMID- 20819173
TI  - Trait correlates and functional significance of heteranthery in flowering plants.
AB  - * Flowering plants display extraordinary diversity in the morphology of male
      sexual organs, yet the functional significance of this variation is not well
      understood. Here, we conducted a comparative analysis of floral correlates of
      heteranthery - the morphological and functional differentiation of anthers within
      flowers - among angiosperm families to identify traits associated with this
      condition. * We performed a phylogenetic analysis of correlated evolution between
      heteranthery and several floral traits commonly reported from heterantherous
      taxa. In addition, we quantified the effect of phylogenetic uncertainty in the
      observed patterns of correlated evolution by comparing trees in which polytomous
      branches were randomly resolved. * Heteranthery is reported from 12 angiosperm
      orders and is phylogenetically associated with the absence of floral nectaries,
      buzz-pollination and enantiostyly (mirror-image flowers). These associations are
      robust to particularities of the underlying phylogenetic hypothesis. *
      Heteranthery has probably evolved as a result of pollinator-mediated selection
      and appears to function to reduce the conflict of relying on pollen both as food
      to attract pollinators and as the agent of male gamete transfer. The relative
      scarcity of heteranthery among angiosperm families suggests that the conditions
      permitting its evolution are not easily met despite the abundance of pollen
      collecting bees and nectarless flowers.

PMID- 20819172
TI  - Fusion between human mesenchymal stem cells and rodent cerebellar Purkinje cells.
AB  - AIMS: we explored whether cellular fusion and heterokaryon formation between
      human and rodent cells in the cerebellum of mice occurs after intravenous
      injection of human bone marrow-derived mesenchymal stem cells (MSCs). The
      influence of central nervous system inflammation on this process was also
      assessed. In addition, we examined whether tumour necrosis factor (TNF)-alpha and
      interferon (IFN)-gamma, factors associated with inflammation, increase cellular
      fusion between human MSCs and rodent cerebellar neurons in vitro. METHODS AND
      RESULTS: human MSCs were intravenously injected into mice with experimental
      autoimmune encephalomyelitis (EAE) and control mice. After 22 days, mouse
      Purkinje cells expressing human Golgi Zone were found within the Purkinje cell
      layer of the cerebellum, indicating that fusion and heterokaryon formation had
      occurred. The numbers of heterokaryons in the cerebellum were markedly increased
      in mice with EAE compared with control mice. Rodent cerebellar neuronal cells
      labelled with enhanced green fluorescent proteinin vitro were co-cultured with
      human bone marrow-derived MSCs in the presence of TNF-alpha and/or IFN-gamma to
      determine their influence on fusion events. We found that fusion between MSCs and
      cerebellar neurons did occur in vitro and that the frequency of cellular fusion
      increased in the presence of TNF-alpha and/or IFN-gamma. CONCLUSIONS: we believe
      that this is the first paper to define fusion and heterokaryon formation between
      human MSCs and rodent cerebellar neurons in vivo. We have also demonstrated that
      fusion between these cell populations occurs in vitro. These findings indicate
      that MSCs may be potential therapeutic agents for cerebellar diseases, and other
      neuroinflammatory and neurodegenerative disorders.

PMID- 20819174
TI  - Fire and the spread of flowering plants in the Cretaceous.
AB  - We suggest that the spread of angiosperms in the Cretaceous was facilitated by
      novel fire regimes. Angiosperms were capable of high productivity and therefore
      accumulated flammable biomass ('fuel') more rapidly than their predecessors. They
      were capable of rapid reproduction, allowing populations to spread despite
      frequent disturbance. We evaluate the evidence for physical conditions conducive
      to fires in the Cretaceous. These included high temperatures, seasonally dry
      climate and higher atmospheric oxygen than current levels. We evaluate novel
      properties of angiosperms that contributed to rapid biomass accumulation, and to
      their ability to thrive in frequently disturbed environments. We also review
      direct evidence for Cretaceous fires. Charcoal mesofossils are common in
      Cretaceous deposits of the Northern Hemisphere. Inertinite, the charcoal
      component of coal, is common throughout the Cretaceous and into the Palaeocene,
      but declined steeply from the Eocene when angiosperm-dominated forests became
      widespread. Direct and indirect evidence is consistent with angiosperms
      initiating novel fire regimes, promoting angiosperm spread in the Cretaceous.
      Several traits are consistent with frequent surface fires. We suggest that forest
      was slow to develop until the Eocene, when fire activity dropped to very low
      levels. The causes and consequences of fires in the deep past warrant greater
      attention.

PMID- 20819175
TI  - Early response of plant cell to carbon deprivation: in vivo 31P-NMR spectroscopy
      shows a quasi-instantaneous disruption on cytosolic sugars, phosphorylated
      intermediates of energy metabolism, phosphate partitioning, and intracellular
      pHs.
AB  - * In plant cells, sugar starvation triggers a cascade of effects at the scale of
      1-2 days. However, very early metabolic response has not yet been investigated. *
      Soluble phosphorus (P) compounds and intracellular pHs were analysed each 2.5 min
      intervals in heterotrophic sycamore (Acer pseudoplatanus) cells using in vivo
      phosphorus nuclear magnetic resonance ((31)P-NMR). * Upon external-sugar
      withdrawal, the glucose 6-P concentration dropped in the cytosol, but not in
      plastids. The released inorganic phosphate (Pi) accumulated transiently in the
      cytosol before influx into the vacuole; nucleotide triphosphate concentration
      doubled, intracellular pH increased and cell respiration decreased. It was
      deduced that the cytosolic free-sugar concentration was low, corresponding to
      only 0.5 mM sucrose in sugar-supplied cells. * The release of sugar from the
      vacuole and from plastids is insufficient to fully sustain the cell metabolism
      during starvation, particularly in the very short term. Similarly to Pi
      starvation, the cell's first response to sugar starvation occurs in the cytosol
      and is of a metabolic nature. Unlike the cytoplasm, cytosolic homeostasis is not
      maintained during starvation. The important metabolic changes following cytosolic
      sugar exhaustion deliver early endogenous signals that may contribute to trigger
      rescue metabolism.

PMID- 20819176
TI  - The metabolic theory of ecology: prospects and challenges for plant biology.
AB  - The metabolic theory of ecology (MTE) as applied to the plant sciences aims to
      provide a general synthesis for the structure and functioning of plants from
      organelles to ecosystems. MTE builds from simple assumptions of individual
      metabolism to make predictions about phenomena across a wide range of scales,
      from individual plant structure and function to community dynamics and global
      nutrient cycles. The scope of its predictions include morphological allometry,
      biomass partitioning, vascular network design, and life history phenomena at the
      individual level; size-frequency distributions, population growth rates, and
      energetic equivalence at the community level; and the flux, turnover and storage
      of nutrients at the ecosystem level. Here, we provide an overview of MTE, by
      considering its assumptions and predictions at these different levels of
      organization and explaining how the model integrates phenomena among all of these
      scales. We highlight the model's many successes in predicting novel patterns and
      draw attention to areas in which gaps remain between observations and MTE's
      assumptions and predictions. Considering the theory as a whole, we argue that MTE
      has made a significant contribution in furthering our understanding of those
      unifying aspects of the structure and function of plants, populations,
      communities, and ecosystems.

PMID- 20819177
TI  - Characterization of foliar manganese (Mn) in Mn (hyper)accumulators using X-ray
      absorption spectroscopy.
AB  - Plant hyperaccumulation of the essential nutrient manganese (Mn) is a rare
      phenomenon most evident in the Western Pacific region, and differs from
      hyperaccumulation of other elements. Mn hyperaccumulators employ a variety of
      species-dependent spatial distribution patterns in sequestering excess foliar Mn,
      including primary sequestration in both nonphotosynthetic and photosynthetic
      tissues. This investigation employed synchrotron X-ray absorption spectroscopy
      (XAS) in a comparative study of Mn (hyper)accumulators, to elucidate in situ the
      chemical form(s) of foliar Mn in seven woody species from Australia, New
      Caledonia and Japan. Foliar Mn was found to predominate as Mn(II) in all samples,
      with strong evidence of the role of carboxylic acids, such as malate or citrate,
      as complexing ligands. Overall, the X-ray absorption near-edge spectroscopy
      (XANES) and extended X-ray absorption fine-structure spectroscopy (EXAFS) data
      appeared weighted against previous observations that oxalate binds excess Mn in
      Mn-(hyper)accumulating species.

PMID- 20819178
TI  - Day-length effects on carbon stores for respiration of perennial ryegrass.
AB  - * The mechanism controlling the use of stored carbon in respiration is poorly
      understood. Here, we explore if the reliance on stores as respiratory substrate
      depends on day length. * Lolium perenne (perennial ryegrass) was grown in
      continuous light (275 MUmol photons m(-2) s(-1) ) or in a 16 : 8 h day : night
      regime (425 MUmol m(-2) s(-1) during the photoperiod), with the same daily
      photosynthetic photon flux density (PPFD). Plants in stands were labelled with
      (13)CO(2) : (12)CO(2) for various time intervals. The rates and isotopic
      signatures of shoot- and root-respired CO(2) were measured after labelling, and
      water-soluble carbohydrates were determined in biomass. The tracer kinetics in
      respired CO(2) was analysed with compartmental models to infer the sizes, half
      lives and contributions of respiratory substrate pools. * Stores were the main
      source for respiration in both treatments (c. 60% of all respired carbon). But,
      continuous light slowed the turnover (+270%) and increased the size (+160%) of
      the store relative to the 16 : 8 h day : night regime. This effect corresponded
      with a greatly elevated fructan content. Yet, day length had no effect on sizes
      and half-lives of other pools serving respiration. * We suggest that the
      residence time of respiratory carbon was strongly influenced by partitioning of
      carbon to fructan stores.

PMID- 20819180
TI  - Comparison of generic tacrolimus and Prograf drug levels in a pediatric kidney
      transplant program: brief communication.
AB  - A generic version of tacrolimus was approved for use in the USA in August 2009.
      These narrow therapeutic index generics are tested for bioequivalence only in
      adults. No data are available on generic tacrolimus levels in children with
      allografts. Four patients with stable renal allografts in our pediatric program
      were inadvertently switched to generic tacrolimus. We retrospectively analyzed
      pre- and post-switch trough tacrolimus and serum creatinine levels. Twelve-h
      trough tacrolimus levels (mean +/- s.e.) were (i) patient 1 (12-yr-old girl): 7.0
      +/- 0.69 and 9.7 +/- 3.5 (p =NS); (ii) patient 2 (eight-yr-old boy): 4.7 +/- 0.68
      and 3.4 +/- 0.84 (p = 0.04); (iii) patient 3 (22-yr-old woman): 6.8 +/- 0.17 and
      6.6 +/- 0.4 (p = NS); (iv) patient 4 (20-yr-old woman): 5.4 +/- 0.25 and 4.9 +/-
      1.4 (p = NS). Creatinine levels were similar pre- and post-switch (eGFR > 75
      mL/min/1.73 m2) in the first three. Patient 4 experienced a biopsy proven acute
      rejection immediately after switching. Mean creatinine rose from 1.15 +/- 0.05 to
      2.168 +/- 0.07 after switch (p < 0.001). Given our mixed picture with the early
      data, we suggest careful monitoring of pediatric patients who get switched to
      generic tacrolimus.

PMID- 20819179
TI  - A role for pectin de-methylesterification in a developmentally regulated growth
      acceleration in dark-grown Arabidopsis hypocotyls.
AB  - * We focused on a developmentally regulated growth acceleration in the dark-grown
      Arabidopsis hypocotyl to study the role of changes in cell wall metabolism in the
      control of cell elongation. * To this end, precise transcriptome analysis on
      dissected dark-grown hypocotyls, Fourier transform infrared (FT-IR)
      microspectroscopy and kinematic analysis were used. * Using a cellulose synthesis
      inhibitor, we showed that the growth acceleration marks a developmental
      transition during which growth becomes uncoupled from cellulose synthesis. We
      next investigated the cellular changes that take place during this transition. FT
      IR microspectroscopy revealed significant changes in cell wall composition
      during, but not after, the growth acceleration. Transcriptome analysis suggested
      a role for cell wall remodeling, in particular pectin modification, in this
      growth acceleration. This was confirmed by the overexpression of a pectin
      methylesterase inhibitor, which caused a delay in the growth acceleration. * This
      study shows that the acceleration of cell elongation marks a developmental
      transition in dark-grown hypocotyl cells and supports a role for pectin de
      methylesterification in the timing of this event.

PMID- 20819181
TI  - Indications for hematopoietic cell transplantation for children with severe
      congenital neutropenia.

PMID- 20819182
TI  - Transient hyperphosphatasemia in pediatric renal transplant patients--is there a
      need for concern and when?
AB  - TH of infancy and early childhood is characterized by transiently increased S
      ALP, predominantly its bone or liver isoforms. There are neither signs of
      metabolic bone disease or hepatopathy corresponding to the increased S-ALP, nor a
      common underlying/triggering disease. TH may also occur in children post-renal
      Tx, which may raise significant concerns and anxiety. We describe four patients
      aged 2.8-7 yr in whom the TH occurred at 11-34 (median = 28) months after Tx and
      lasted from 40 to 105 (median = 63) days. No obvious cause/trigger of TH could be
      found; the clinical status and bone turnover were not altered. In cases of TH
      post-Tx, we recommend the evaluation of basic biochemical indices and wrist X
      ray. If these results are normal, TH is most likely the diagnosis and the S-ALP
      can be monitored over the next three months without further testing. In patients
      with persisting TH for more than three months and/or in children with pre
      existing or suspected metabolic bone disease, further evaluation may be
      indicated. In conclusion, TH is a benign disorder in patients post-Tx. Detailed
      investigation including bone biopsy is only indicated in patients with persisting
      TH.

PMID- 20819183
TI  - Living related liver transplant following bone marrow transplantation from same
      donor: long-term survival without immunosuppression.
AB  - We report long-term (seven yr) immunological tolerance in a 16-yr-old boy, to a
      liver allograft donated by his father following a bone marrow transplant at age
      2.5 yr from the same donor. The bone marrow transplant was complicated by severe
      GVHD leading to liver failure and the ensuing need for a liver transplant,
      performed under planned avoidance of immunosuppression. At one wk post
      transplant, although a liver biopsy was histologically compatible with acute
      rejection, favorable clinical and biochemical evolution precluded initiating
      immunosuppressive therapy, thus highlighting the need for caution when
      interpreting early histological changes so that administration of unnecessary
      immunosuppression can be avoided. Induction of tolerance in transplant recipients
      remains an elusive goal. In those patients who had received conventional bone
      marrow transplants and had endured the consequences of GVHD, development of
      macrochimerism may allow immunosuppression-free solid organ transplantation from
      the same donor.

PMID- 20819184
TI  - Living donor liver transplantation using a graft from a donor with Dubin-Johnson
      syndrome.
AB  - DJS is an autosomal recessive disorder that causes an increase in conjugated
      bilirubin without elevation of liver enzymes. Most patients are asymptomatic and
      have normal life spans, but to the best of our knowledge, their livers have never
      been reported to be grafts in liver transplantation. Herein, we report an infant
      patient with MMA that received a partial liver graft from his mother, who had
      DJS. A biliary anastomosis stricture was noted five months after transplantation
      and was successfully treated with radiological interventions. Otherwise, the
      patient's liver functions were normal, and a liver biopsy showed a pathognomonic
      picture of DJS nine months after the transplantation. The patient was followed
      for one yr, and the results were satisfactory for an increase in oral intake and
      protein uptake, no recurrence of metabolic stroke and there was a gradual catch
      up with regard to physical development despite having a persistently abnormal
      profile of amino acid analysis. From the experience of our case, we suggest that
      a liver from a donor with DJS can be used as a graft for liver transplantation,
      although long-term follow-up is mandatory to examine the grafted liver under the
      use of immunosuppressive medications.

PMID- 20819185
TI  - A case of pediatric PTLD following autologous stem cell transplantation and
      review of the literature.
AB  - The development of PTLD is a rare severe adverse event following ASCT. We report
      on a child with DS who developed PTLD following autologous transplant for
      relapsed Hodgkin's disease. He was successfully treated with cyclophosphamide,
      prednisone and rituximab. We also present a comprehensive review of the
      literature of PTLD in pediatric patients following ASCT.

PMID- 20819186
TI  - Downregulation of SIK2 expression promotes the melanogenic program in mice.
AB  - cAMP response element-binding protein (CREB) promotes melanogenesis by inducing
      microphthalmia-associated transcription factor (Mitf ) gene expression. We report
      here that the CREB-specific coactivator TORC and its repressor, salt-inducible
      kinase 2 (SIK2), are fundamental determinants of the melanogenic program in mice.
      Exposure of B16 melanoma cells to ultraviolet (UV) light results in the immediate
      nuclear translocation of TORC1, which is inhibited by SIK2. Overexpression of
      dominant-negative TORC1 also inhibits UV-induced Mitf gene expression and
      melanogenesis. alpha-MSH signaling regulates hair pigmentation, and the decrease
      in alpha-MSH activity in hair follicle melanocytes switches the melanin synthesis
      from eumelanin (black) to pheomelanin (yellow). Mice with the lethal yellow
      allele of agouti (A(y)) have yellow hair because of impaired activation of the
      alpha-MSH receptor. To examine the involvement of SIK2 in the regulation of the
      melanogenesis switch in vivo, we prepared SIK2-knockout mice, and the Sik2(-/-)
      genotype was introduced into A(y)/a mice. The resultant Sik2(-/-); A(y)/a mice
      had brown hair, indicating that SIK2 represses eumelanogenesis in mice.

PMID- 20819187
TI  - Decreased heme oxygenase-1 expression distinguishes human melanomas from
      melanocytic nevi.

PMID- 20819188
TI  - Assistant nurses working in care of older people: associations with sustainable
      work ability.
AB  - Indicators of health have shown improvements in the Swedish working population
      during the past decades, but with the exception of low-skilled women. Earlier
      research has shown that assistant nurses belong to an occupational group, which
      has the lowest share of individuals with long-term health in the total Swedish
      workforce. Sick leave research has mostly focused on determining risk factors for
      the development of diseases and dysfunctions. In the process of acquiring
      knowledge about mechanisms for sick leave, it has become obvious that there is
      also a need to focus on what contributes to work ability. The aim in this study
      was to explore what promotes sustainable work ability in female assistant nurses
      working in care of older people. Associations between factors related to work,
      health, lifestyle and sustainable work ability were investigated in a cross
      sectional nested case-control study in a cohort of 366 female assistant nurses.
      Data were collected in self-reports in a questionnaire. Odds ratios were
      calculated, and a multiple logistic regression analysis was performed with
      sustainable work ability as the dependent variable. Sustainable work ability was
      associated with good self-rated health, a BMI <30, ability to sleep well,
      recuperation, low stress level, support from family and friends, being over 25
      years of age at birth of the first child, and control over one's own life in the
      >=50 age group. In the logistic regression analysis, the significant associations
      were good self-rated health, being over 25 years of age at the birth of the first
      child and recuperation. In conclusion, the study showed that self-rated health
      and factors in private life are important for assistant nurse's sustainable work
      ability over time. The results from this study could be applied in health
      promotion work for employees in the care sector to strengthen and enhance
      sustainable work ability.

PMID- 20819189
TI  - The emergence of cellular therapy: impact on transfusion medicine.

PMID- 20819190
TI  - Role of heme oxygenase-1 in transplantation.
AB  - Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in heme catabolism that
      converts heme to Fe++, carbon monoxide and biliverdin. HO-1 acts anti
      inflammatory and modulates apoptosis in many pathological conditions. In
      transplantation, HO-1 is overexpressed in organs during brain death, when
      undergoing ischemic damage and rejection. However, intentionally induced, it
      ameliorates pathological processes like ischemia reperfusion injury, allograft,
      xenograft or islet rejection, facilitates donor specific tolerance and alleviates
      chronic allograft changes. We herein consistently summarize the huge amount of
      data on HO-1 and transplantation that have been generated in multiple
      laboratories during the last 15years and suggest possible clinical implications
      and applications for the near future.

PMID- 20819191
TI  - How important is the duration of the brain death period for the outcome in kidney
      transplantation?
AB  - In kidney transplantation, graft survival using grafts from donation after brain
      death (DBD) donors is inferior to results after living donation. However, little
      is known about the effect of the duration of brain death (BDdur) on outcome after
      transplantation. This is a retrospective Organ Procurement and Transplant Network
      analysis using kidney donor and recipient data from 1994 to 2006. BDdur was
      calculated as the period between brain death declaration and aortic cross clamp.
      Effects of BDdur on delayed graft function (DGF), acute rejection and graft
      failure were calculated using binary logistic regression and Cox regression
      models. Median BDdur was 23.8 h. Longer BDdur decreased the risk for DGF and 1-
      and 3-year graft failure slightly, but not for acute rejection. In multivariate
      analysis, donor age and acute rejection were confounders. However, in a
      multivariate subgroup analysis of donors aged <= 55 years BDdur independently
      predicted DGF; each hour of BDdur decreasing the risk of DGF with 0.4% (P =
      0.008). Longer BDdur is not detrimental and in fact slightly beneficial in DBD
      donors <= 55 years of age, reducing the chance of DGF in the recipient. This
      finding may have an impact on organ retrieval procedures, as no rush but rather
      an improved donor management prior to retrieval will benefit donor kidney
      viability.

PMID- 20819192
TI  - Assessment of renal allograft fibrosis by acoustic radiation force impulse
      quantification--a pilot study.
AB  - Chronic allograft nephropathy characterized by interstitial fibrosis and tubular
      atrophy is a major cause of renal transplant failure. Acoustic radiation force
      impulse (ARFI) quantification is a promising noninvasive method for assessing
      tissue stiffness. We evaluated if the method could reveal renal transplant
      fibrosis. In a prospective study, 30 adult renal transplant recipients were
      included. ARFI quantification, given as shear wave velocity (SWV), of the renal
      cortex was performed by two observers. SWV was compared to grade of fibrosis (0
      3) in biopsies. The median SWV was 2.8 m/s (range: 1.6-3.6), 2.6 m/s (range: 1.8
      3.5) and 2.5 m/s (range: 1.6-3) for grade 0 (n = 12), 1 (n = 10) and grades 2/3
      (n = 8) fibrosis respectively. SWV did not differ significantly in transplants
      without and with fibrosis (grade 0 vs. grade 1, P = 0.53 and grade 0 vs. grades
      2/3, P = 0.11). The mean intraobserver coefficient of variation was 22% for
      observer 1 and 24% for observer 2. Interobserver agreement, expressed as
      intraclass correlation coefficient was 0.31 (95% CI: -0.03 to 0.60). This study
      does not support the use of ARFI quantification to assess low-grade fibrosis in
      renal transplants. ARFI quantification in its present stage of development has
      also high intra- and interobserver variation in renal transplants.

PMID- 20819193
TI  - Machine perfusion cost-effectiveness versus cold storage has been demonstrated;
      limiting use to marginal donor kidneys unjustified.

PMID- 20819194
TI  - Glucose-6-phosphate dehydrogenase deficiency: a contraindication for living donor
      liver transplantation?

PMID- 20819195
TI  - Molecular biomarker candidates of acute kidney injury in zero-hour renal
      transplant needle biopsies.
AB  - The aim of this study was to assess gene expression levels of four biomarker
      candidates [lipocalin 2 (LCN2), the kidney injury molecule 1 (HAVCR1), netrin 1,
      and the cysteine-rich, angiogenic inducer, 61] in the tubulointerstitial and the
      glomerular compartment of zero-hour kidney biopsies in order to predict
      developing delayed graft function (DGF). Thirty-four needle kidney biopsy samples
      of deceased donors were manually microdissected. Relative gene expression levels
      were determined by real-time RT-PCR. For the validation of the biomarker
      candidates, we calculated a mixed model comparing kidneys with DGF, primary
      function and control samples from the healthy parts of tumor nephrectomies.
      Significant biomarker candidates were analyzed together with donor age in
      multivariable regression models to determine the prognostic value. Expression
      levels of LCN2 and HAVCR1 in the tubulointerstitium were significantly
      upregulated in the DGF group (LCN2: fold change = 3.78, P = 0.031 and HAVCR1:
      fold change = 3.44, P = 0.010). Odds ratios of both genes could not reach
      significance in the multivariable model together with donor age. The area under
      the curve of the receiver operating characteristic ranges between 0.75 and 0.83.
      LCN2 and HAVCR1 gene expression levels in zero-hour biopsies show potential to
      act as early biomarkers for DGF.

PMID- 20819196
TI  - Multicentric evaluation of model for end-stage liver disease-based allocation and
      survival after liver transplantation in Germany--limitations of the 'sickest
      first'-concept.
AB  - Since the introduction of model for end-stage liver disease (MELD) in 2006, post
      orthotopic liver transplantation (OLT) survival in Germany has declined. The aim
      of this study was to evaluate risk factors and prognostic scores for outcome. All
      adult OLT recipients in seven German transplant centers after MELD implementation
      (December 2006-December 2007) were included. Recipient data were analyzed for
      their influence on 1-year outcome. A total of 462 patients (mean calculated MELD
      = 20.5, follow-up: 1 year) were transplanted for alcoholic cirrhosis (33.1%),
      hepatocellular carcinoma (26.6%), Hepatitis-C (17.1%), Hepatitis-B (9.5%),
      primary sclerosing cholangitis (5.6%) and late graft-failure after first OLT
      before December 2006 (8.7%). 1-year patient survival was 75.8% (graft survival
      71.2%) correlating with MELD parameters and serum choline esterase. MELD score
      >30 [odds ratio (OR) = 4.17, confidence interval: 2.57-6.78, 12-month survival =
      52.6%, c-statistic = 0.669], hyponatremia (OR = 2.07), and pre-OLT hemodialysis
      (OR = 2.35) were the main death risk factors. In alcoholic cirrhosis (n = 153,
      mean MELD = 21.1) and hepatocellular carcinoma (n = 123, mean MELD = 13.5), serum
      bilirubin and the survival after liver transplantation score were independent
      outcome parameters, respectively. MELD >30 currently represents a major risk
      factor for outcome. Risk factors differ in individual patient subgroups. In the
      current German practice of organ allocation to sicker patients, outcome
      prediction should be considered to prevent results below acceptable standards.

PMID- 20819198
TI  - Nursing interventions to improve outcomes in hospitalized adults.

PMID- 20819197
TI  - Long-term engraftment and function of transplanted pancreatic islets in
      vascularized segments of small intestine.
AB  - This study evaluated the potential of vascularized small intestinal segments for
      pancreatic islet transplantation. Islets isolated from Lewis rats were
      transplanted into diabetic syngeneic recipients. Segments of small intestine were
      prepared by denudation of the mucosal layer prior to implantation of pancreatic
      islets into the segments. Animal groups were established to determine
      engraftment, survival and function of islets transplanted into either intestinal
      segments or portal vein over up to 60 days. We found transplantation of
      functionally intact pancreatic islets into small intestinal segments was well
      tolerated. Transplanted islets were rapidly engrafted in intestinal segments as
      demonstrated vascularization and expression of insulin and glucagon throughout
      the 60-day duration of the studies. Transplantation of islets restored euglycemia
      in diabetic rats, which was similar to animals receiving islets intraportally.
      Moreover, animals treated with islet transplants showed normal responses to
      glucose challenges. Removal of graft-bearing intestinal segments led to
      recurrence of hyperglycemia indicating that transplanted islets were responsible
      for improved outcomes. Therefore, we concluded that vascularized intestinal
      segments supported reorganization, survival and function of transplanted islets
      with therapeutic efficacy in streptozotocin-treated diabetic rats. The approach
      described here will be appropriate for studying islet biogenesis, reorganization
      and function, including for cell therapy applications.

PMID- 20819199
TI  - Multidisciplinary team developed and implemented protocols to assist mechanical
      ventilation weaning: a systematic review of literature.
AB  - AIM: The aim of this review was to determine if ventilation-weaning protocols
      developed and implemented by multidisciplinary teams (MDTs) reduced the duration
      of mechanical ventilation in adult intensive care patients compared to usual
      care. METHOD: A systematic review was conducted to review published research
      studies from January 1999 to June 2009 to identify and analyse the best available
      evidence on MDT-based weaning protocols in adult intensive care patients. All
      relevant studies based on electronic searches of MEDLINE, EMBASE, CINAHL, the
      Cochrane Controlled Trials Registry and the Cochrane Database of Systematic
      Reviews were included. Where possible data were pooled and a meta-analysis
      performed. A narrative synthesis of data was conducted to provide a critical
      appraisal of nonrandomised controlled trials included in the review. RESULTS:
      Three pre- and postinterventional studies were identified for inclusion in this
      review. Results show equivocal support for weaning protocols developed and
      implemented by MDTs for reducing duration of mechanical ventilation. CONCLUSION:
      Communication and organizational processes must be addressed for
      multidisciplinary protocols to be effective. Due to methodological limitations of
      included studies, large randomised controlled trials are required to provide high
      level evidence of the effects of MDT-based protocols on duration of mechanical
      ventilation.

PMID- 20819200
TI  - Animal health policy principles for highly pathogenic avian influenza: shared
      experience from China and Canada.
AB  - Animal health policy for highly pathogenic avian influenza (HPAI) must, for the
      time being, be based on expert opinion and shared international experience. We
      used the intellectual capital and knowledge of experienced Chinese and Canadian
      practitioners and policy makers to inform policy options for China and find
      shared policy elements applicable to both countries. No peer-reviewed
      comprehensive evaluations or systematic regulatory impact assessments of animal
      health policies were found. Sixteen guiding policy principles emerged from our
      thematic analysis of Chinese and Canadian policies. We provide a list of shared
      policy goals, targets and elements for HPAI preparedness, response and recovery.
      Policy elements clustered in a manner consistent with core public health
      competencies. Complex situations like HPAI require complex and adaptive policies,
      yet policies that cross jurisdictions and are fully integrated across agencies
      are rare. We encourage countries to develop or deploy capacity to undertake and
      publish regulatory impact assessments and policy evaluation to identify policy
      needs and provide a basis for evidence-based policy development.

PMID- 20819201
TI  - A retrospective economic analysis of the Ontario red fox oral rabies vaccination
      programme.
AB  - Ontario initiated a red fox (Vulpes vulpes) oral rabies vaccination (ORV)
      programme in 1989. This study utilized a benefit-cost analysis to determine if
      this ORV programme was economically worthwhile. Between 1979 and 1989, prior to
      ORV baiting, the average annual human post-exposure treatments, positive red fox
      rabies diagnostic tests and indemnity payments for livestock lost to rabies were
      2248, 1861 and $246,809, respectively. After baiting, from 1990 to 2000, a 35%,
      66% and 41% decrease in post-exposure treatments, animal rabies tests and
      indemnity payments was observed, respectively. These reductions were viewed as
      benefits of the ORV programme, whereas total costs were those associated with ORV
      baiting. Multiple techniques were used to estimate four different benefit streams
      and the total estimated benefits ranged from $35,486,316 to $98,413,217. The
      annual mean ORV programme cost was $6,447,720, with total programme costs of
      $77,372,637. The average benefit-cost ratios over the analysis period were .49,
      1.06, 1.27 and 1.36, indicating overall programme efficiency in three of the four
      conservative scenarios.

PMID- 20819202
TI  - Genetic variations in Shiga toxin-producing abilities of bovine and human
      Escherichia coli O157:H7.
AB  - Cattle are a primary reservoir of Escherichia coli O157:H7, a major foodborne
      pathogen. The organism causes haemorrhagic colitis which can lead to serious
      complications, including haemolytic-uraemic syndrome. Although E. coli O157:H7 is
      widely prevalent in cattle and cattle environments, the number of human cases
      remain relatively low, suggesting possible strain diversity and differences in
      virulence between human and bovine strains. Shiga toxins, Stx1 and Stx2, are the
      major virulence factors. Differences in Stx2 production between human and bovine
      strains have been demonstrated previously, and isolates possessing the stx2 gene,
      but not producing Stx2 [toxin non-producing (TNP) strains] have been identified.
      In this study, 150 isolates (56 human, 94 bovine) were tested by PCR for stx2
      upstream regions associated with TNP and the Q933 gene, which has been previously
      associated with toxin production. A reverse passive latex agglutination test was
      used to evaluate 107 isolates (50 human, 57 bovine) for Stx1 and Stx2 production.
      The percentages of human and bovine isolates positive for presence of the TNP
      regions were similar (57.1% and 53.1% respectively), while a higher percentage of
      human isolates was positive for Q933 gene (89.3% versus 54.3%). Stx2 production
      of >= 1:8 was found in 86.0% of human isolates compared with 26.3% of bovine
      isolates. Bovine isolates with the presence of the TNP regions were associated
      with significantly lower Stx2 production (P < 0.05), while the Q933 gene was
      associated with higher Stx2 production (P < 0.05). However, the presence of the
      TNP region was not associated (P > 0.05) with low Stx2 production in human
      isolates. Therefore, Q933 was a better indicator of high Stx2 production by human
      and bovine isolates and may be a useful screening method to assess their
      potential to cause human disease.

PMID- 20819203
TI  - A follow-up study of the fate of small asymptomatic deep venous thromboses.
AB  - BACKGROUND: Postoperative asymptomatic deep venous thromboses (ADVT) can give
      rise to posttthrombotic syndrome (PTS), but there are still many unresolved
      issues in this context. For example, there is a lack of knowledge regarding the
      fate of small ADVT following minor orthopedic surgery. This follow-up study
      evaluates postthrombotic changes and clinical manifestations of PTS in a group of
      patients with asymptomatic calf vein DVT after surgery for Achilles tendon
      rupture. METHODS: Forty-six consecutive patients with distal ADVT were contacted
      and enrolled in a follow-up consisting of a single visit at the hospital at a
      mean time of 5 years postoperatively, including clinical examination and scoring,
      ultrasonography and venous plethysmography. All patients had participated in DVT
      screening with colour duplex ultrasound (CDU) 3 and 6 weeks postoperatively and
      80% of them were treated with anticoagulation. RESULTS: With CDU postthrombotic
      changes and deep venous reflux were detected at follow-up in more than 50% of the
      patients, more commonly in somewhat larger calf DVT:s initially affecting more
      than one vessel. However, only about 10% of the patients had significant venous
      reflux according to venous plethysmography. No patient had plethysmographic
      evidence of remaining outflow obstruction, but presence of postthrombotic changes
      shown with CDU negatively influenced venous outflow capacity measured with
      plethysmography. A clinical entity of PTS was rarely found and occurred only in
      two patients (4%) and then classified by Villalta scoring as of mild degree with
      few clinical signs of disease. Distal ADVT:s detected in the early postoperative
      period (3 weeks) showed DVT-progression in 75% of the limbs that were still
      immobilized and without anticoagulation. CONCLUSIONS: Asymptomatic postoperative
      distal DVT:s following surgery for Achilles tendon rupture have a good prognosis
      and a favourable clinical outcome. In our material of 46 patients the general
      appearance of the clinical entity of PTS at 5 years follow-up was low (<5%).
      Morphological and functional abnormalities were mainly seen in those patients
      that initially had somewhat larger distal DVT:s involving more than one deep calf
      vein segment.

PMID- 20819204
TI  - OpenMEEG: opensource software for quasistatic bioelectromagnetics.
AB  - BACKGROUND: Interpreting and controlling bioelectromagnetic phenomena require
      realistic physiological models and accurate numerical solvers. A semi-realistic
      model often used in practise is the piecewise constant conductivity model, for
      which only the interfaces have to be meshed. This simplified model makes it
      possible to use Boundary Element Methods. Unfortunately, most Boundary Element
      solutions are confronted with accuracy issues when the conductivity ratio between
      neighboring tissues is high, as for instance the scalp/skull conductivity ratio
      in electro-encephalography. To overcome this difficulty, we proposed a new method
      called the symmetric BEM, which is implemented in the OpenMEEG software. The aim
      of this paper is to present OpenMEEG, both from the theoretical and the practical
      point of view, and to compare its performances with other competing software
      packages. METHODS: We have run a benchmark study in the field of electro- and
      magneto-encephalography, in order to compare the accuracy of OpenMEEG with other
      freely distributed forward solvers. We considered spherical models, for which
      analytical solutions exist, and we designed randomized meshes to assess the
      variability of the accuracy. Two measures were used to characterize the accuracy.
      the Relative Difference Measure and the Magnitude ratio. The comparisons were
      run, either with a constant number of mesh nodes, or a constant number of
      unknowns across methods. Computing times were also compared. RESULTS: We observed
      more pronounced differences in accuracy in electroencephalography than in
      magnetoencephalography. The methods could be classified in three categories: the
      linear collocation methods, that run very fast but with low accuracy, the linear
      collocation methods with isolated skull approach for which the accuracy is
      improved, and OpenMEEG that clearly outperforms the others. As far as speed is
      concerned, OpenMEEG is on par with the other methods for a constant number of
      unknowns, and is hence faster for a prescribed accuracy level. CONCLUSIONS: This
      study clearly shows that OpenMEEG represents the state of the art for forward
      computations. Moreover, our software development strategies have made it handy to
      use and to integrate with other packages. The bioelectromagnetic research
      community should therefore be able to benefit from OpenMEEG with a limited
      development effort.

PMID- 20819205
TI  - Lowering the apoptotic threshold in colorectal cancer cells by targeting
      mitochondria.
AB  - BACKGROUND: Colorectal cancer is the third most-common cancer and the second most
      common cause of cancer related death in UK. Although chemotherapy plays
      significant role in the treatment of colorectal cancer, morbidity and mortality
      due to drug resistance and cancer metastasis are yet to be eliminated. Recently,
      doxycycline has been reported to have cytotoxic and anti-proliferating properties
      in various cancer cells. In this study, whether doxycycline was apoptosis
      threshold lowering agent in colorectal cancer cells by targeting mitochondria was
      answered. RESULTS: This study showed dose-dependent cytotoxic effects of
      cisplatin, oxaliplatin and doxycycline in HT29 colorectal cancer cells.
      Doxycycline showed inhibition of cytochrome-c-oxidase activity in these cells
      over a time-period. The pre-treatment of doxycycline reported statistically
      significant increased cytotoxicity of cisplatin and oxaliplatin compared to
      cisplatin and oxaliplatin alone. The caspase studies revealed significantly less
      expression and activity of caspase 3 in HT29 cells pre-treated with doxycycline
      compared to the cells treated with cisplatin and oxaliplatin alone. CONCLUSIONS:
      It was concluded that doxycycline lowered the apoptotic threshold in HT 29 cells
      by targeting mitochondria. This also raised possible caspase-independent
      mechanisms of apoptosis in HT29 cells when pre-treated with doxycycline however
      this needs further research work.

PMID- 20819206
TI  - Regulation of breast cancer cell motility by T-cell lymphoma invasion and
      metastasis-inducing protein.
AB  - INTRODUCTION: T-cell lymphoma invasion and metastasis-inducing protein (Tiam1) is
      a Ras-related C3 botulinum toxin substrate (Rac)-specific guanine nucleotide
      exchange factor that was isolated based on its ability to induce a metastatic
      phenotype. In polarized migrating keratinocytes, Tiam1 is found at the leading
      edge where it cooperates with the Protease-activated receptor 1 (Par1) complex to
      establish front-rear polarity. Although a positive correlation has been observed
      between Tiam1 expression and tumor grade in a variety of human malignancies,
      including breast, its role in breast cancer cells has not yet been examined.
      METHODS: Tiam1 expression and Rac activity were examined in a panel of human
      breast cancer cell lines which exhibit different degrees of cell motility. The
      contribution of Tiam1 to cell motility was directly examined using transwell
      motility, and wound healing assays. RESULTS: Although we observe a striking,
      positive correlation between Tiam1 expression and cell motility in the panel of
      breast cancer cell lines, we do not observe a correlation between Tiam1
      expression and overall levels of Rac activity. Consistent with this, small
      interfering ribonucleic acid (siRNA)-mediated suppression of Tiam1 expression
      limits the motility of cell lines in which Tiam1 expression is high (MDA-MB-231
      and MDA-MB-453), but does not substantially alter the overall levels of activated
      Rac. Tiam1 overexpression is also not sufficient to increase the motility of more
      poorly motile cells (T-47D) or increase Rac activity. Immunofluorescence and
      cellular fractionations indicate that Tiam1 is found predominantly in the Golgi
      of breast cancer cells, and in the latter case Tiam1 was shown to co-fractionate
      with a limited pool of Rac1. Consistent with this Golgi localization, Tiam1
      supports cell motility and Golgi reorientation in response to serum in a wound
      healing assay using MDA-MB-231and MDA-MB-435S cells. CONCLUSIONS: Tiam1
      expression correlates with cell motility in human breast cancer cells, and is
      required to support the motile phenotype. Localization of endogenous Tiam1 to the
      Golgi, and its demonstrated role in Golgi reorientation, suggest that it may
      support motility through a mechanism that is discrete from its known function in
      leading edge dynamics.

PMID- 20819207
TI  - The safety and efficacy of gamma knife surgery in management of glomus jugulare
      tumor.
AB  - BACKGROUND: Glomus jugulare is a slowly growing, locally destructive tumor
      located in the skull base with difficult surgical access. The operative approach
      is, complicated by the fact that lesions may be both intra and extradural with
      engulfment of critical neurovascular structures. The tumor is frequently highly
      vascular, thus tumor resection entails a great deal of morbidity and not
      infrequent mortality. At timeslarge residual tumors are left behind. To decrease
      the morbidity associated with surgical resection of glomus jugulare, gamma knife
      surgery (GKS) was performed as an alternative in 13 patients to evaluate its
      safety and efficacy. METHODS: A retrospective review of 13 residual or
      unresectable glomus jagulare treated with GKS between 2004 and 2008.. Of these,
      11 patients underwent GKS as the primary management and one case each was treated
      for postoperative residual disease and postembolization. The radiosurgical dose
      to the tumor margin ranged between 12-15 Gy. RESULTS: Post- gamma knife surgery
      and during the follow-up period twelve patients demonstrated neurological
      stability while clinical improvement was achieved in 5 patients. One case
      developed transient partial 7th nerve palsy that responded to medical treatment.
      In all patients radiographic MRI follow-up was obtained, the tumor size decreased
      in two cases and remained stable (local tumor control) in eleven patients.
      CONCLUSIONS: Gamma knife surgery provids tumor control with a lowering of risk of
      developing a new cranial nerve injury in early follow-up period. This procedure
      can be safely used as a primary management tool in patients with glomus jugulare
      tumors, or in patients with recurrent tumors in this location. If long-term
      results with GKS are equally effective it will emerge as a good alternative to
      surgical resection.

PMID- 20819208
TI  - Psychological distress among Plains Indian mothers with children referred to
      screening for Fetal Alcohol Spectrum Disorders.
AB  - BACKGROUND: Psychological distress (PD) includes symptoms of depression and
      anxiety and is associated with considerable emotional suffering, social
      dysfunction and, often, with problematic alcohol use. The rate of current PD
      among American Indian women is approximately 2.5 times higher than that of U.S.
      women in general. Our study aims to fill the current knowledge gap about the
      prevalence and characteristics of PD and its association with self-reported
      current drinking problems among American Indian mothers whose children were
      referred to screening for fetal alcohol spectrum disorders (FASD). METHODS:
      Secondary analysis of cross-sectional data was conducted from maternal interviews
      of referred American Indian mothers (n = 152) and a comparison group of mothers
      (n = 33) from the same Plains culture tribes who participated in an NIAAA-funded
      epidemiology study of FASD. Referred women were from one of six Plains Indian
      reservation communities and one urban area who bore children suspected of having
      an FASD. A 6-item PD scale (PD-6, Cronbach's alpha = .86) was constructed with a
      summed score range of 0-12 and a cut-point of 7 indicating serious PD. Multiple
      statistical tests were used to examine the characteristics of PD and its
      association with self-reported current drinking problems. RESULTS: Referred and
      comparison mothers had an average age of 31.3 years but differed (respectively)
      on: education (<high school: 47.4%, 9.1%), PD-6 mean scores (3.57, 1.48), current
      prevalence of serious PD (19.1%, 0.0%), and a current drinking problem (31.6%,
      12.1%). Among referred mothers, those with a current drinking problem had a
      significantly higher mean PD-6 score. Having PD, serious PD, and 2 specific scale
      items significantly increased the odds that a referred mother would have a
      current drinking problem. CONCLUSIONS: Psychological distress among referred
      mothers is significantly associated with having a self-reported drinking problem.
      FASD prevention requires multi-level prevention efforts that provide real
      opportunities for educational attainment and screening and monitoring of PD and
      alcohol use during the childbearing years. Mixed methods studies are needed to
      illuminate the social and cultural determinants at the base of the experience of
      PD and to identify the strengths and protective factors of unaffected peers who
      reside within the same communities.

PMID- 20819209
TI  - One step nucleic acid amplification (OSNA) - a new method for lymph node staging
      in colorectal carcinomas.
AB  - BACKGROUND: Accurate histopathological evaluation of resected lymph nodes (LN) is
      essential for the reliable staging of colorectal carcinomas (CRC). With
      conventional sectioning and staining techniques usually only parts of the LN are
      examined which might lead to incorrect tumor staging. A molecular method called
      OSNA (One Step Nucleic Acid Amplification) may be suitable to determine the
      metastatic status of the complete LN and therefore improve staging. METHODS: OSNA
      is based on a short homogenisation step and subsequent automated amplification of
      cytokeratin 19 (CK19) mRNA directly from the sample lysate, with result available
      in 30-40 minutes. In this study 184 frozen LN from 184 patients with CRC were
      investigated by both OSNA and histology (Haematoxylin & Eosin staining and CK19
      immunohistochemistry), with half of the LN used for each method. Samples with
      discordant results were further analysed by RT-PCR for CK19 and carcinoembryonic
      antigen (CEA). RESULTS: The concordance rate between histology and OSNA was
      95.7%. Three LN were histology+/OSNA- and 5 LN histology-/OSNA+. RT-PCR supported
      the OSNA result in 3 discordant cases, suggesting that metastases were
      exclusively located in either the tissue analysed by OSNA or the tissue used for
      histology. If these samples were excluded the concordance was 97.2%, the
      sensitivity 94.9%, and the specificity 97.9%. Three patients (3%) staged as UICC
      I or II by routine histopathology were upstaged as LN positive by OSNA. One of
      these patients developed distant metastases (DMS) during follow up. CONCLUSION:
      OSNA is a new and reliable method for molecular staging of lymphatic metastases
      in CRC and enables the examination of whole LN. It can be applied as a rapid
      diagnostic tool to estimate tumour involvement in LN during the staging of CRC.

PMID- 20819210
TI  - "Brace Technology" Thematic Series - The ScoliOlogiC(r) Cheneau lightTM brace in
      the treatment of scoliosis.
AB  - BACKGROUND: Bracing concepts in use today for the treatment of scoliosis include
      symmetric and asymmetric hard braces usually made of polyethylene (PE) and soft
      braces. The plaster cast method worldwide seems to be the most practiced
      technique for the construction of hard braces at the moment. CAD (Computer Aided
      Design) systems are available which allow brace adjustments without plaster.
      Another possibility is the use of the ScoliOlogiCTM off the shelf system enabling
      the Certified Prosthetist and Orthotist (CPO) to construct a light brace for
      scoliosis correction from a variety of pattern specific shells to be connected to
      an anterior and a posterior upright. This Cheneau lightTM brace, developed
      according to the Cheneau principles, promises a reduced impediment of quality of
      life in the brace. The correction effects of the first 81 patients (main
      diagnosis Adolescent Idiopathic Scoliosis (AIS) [n = 64] or Early Onset Scoliosis
      (EOS) [n = 15]), treated according to the principles of the Cheneau lightTM brace
      have shown a satisfactory in-brace correction exceeding 50% of the initial Cobb
      angle. BRACE DESCRIPTION: The ScoliOlogiC(r) off the shelf bracing system enables
      the CPO to construct a light brace for scoliosis correction from a variety of
      pattern specific shells to be connected to an anterior and a posterior upright.
      This brace, when finally adjusted is called Cheneau lightTM brace. The advantage
      of this new bracing system is that the brace is available immediately, is easily
      adjustable and that it can also be easily modified. This avoids construction
      periods of sometimes more than 6 weeks, where the curve may drastically increase
      during periods of fast growth. The disadvantage of this bracing system is that
      there is a wide variability of possibilities to arrange the different shells
      during adjustment. RESULTS: The Cobb angle in the whole group was reduced by an
      average of 16,4 degrees , which corresponds to a correction effect of 51%. The
      differences were highly significant in the T-test (T = 17,4; p < 0,001). The best
      correction effects achieved with Cheneau braces reported in literature so far are
      about 40% in two different studies. The correction effect was highest in lumbar
      and thoracolumbar curve patterns (62%; n = 18). In thoracic scoliosis the
      correction effect was 36% (n = 41) and in double major curve patterns 50% (n =
      22). The correction effect was affected in a slightly negative way due to age (r
      = -0,24; p = 0,014), negatively with the Risser stage (-0,29; p = 0,0096) and
      correlated negatively with the Cobb angle measured before treatment (r = -0,43; p
      < 0,0001). CONCLUSIONS: The use of the Cheneau lightTM brace leads to correction
      effects above average when compared to correction effects of other braces
      described in literature. The reduction of material seems to increase patient's
      comfort and reduces the stress patients may suffer from whilst in the brace.80%
      of the adolescent population of scoliosis patients can be braced with the Cheneau
      lightTM brace. In certain patterns of curvature and in the younger population
      with an age of less than 11 years, other approaches have to be used, such as
      plaster based bracing or the application of CAD/CAM based orthoses.

PMID- 20819211
TI  - A rare case of locally advanced fibrosarcoma of diaphysal humerus managed
      successfully with limb-sparing procedures after neoadjuvant chemotherapy.
AB  - Fibrosarcomas (FS) of bone are a rare malignancy accounting for less than 5% of
      all primary malignant bone neoplasms. Diagnosis and treatment approaches of this
      entity are complex and require a skilled and experienced multidisciplinary
      team.Authors report their experience with a case of FS of humerus showing a
      pathologic complete response to neo-adjuvant chemotherapy based on adriamycin,
      cisplatin and ifosfamid. This approach allowed limb-sparing surgery with an
      excellent functional and psychological result.

PMID- 20819212
TI  - In vivo assessment of the impedance ratio method used in electronic foramen
      locators.
AB  - BACKGROUND: The results of an in vivo study on the "ratio method" used in
      electronic foramen locators (EFL) are presented. EFLs are becoming widely used in
      the determination of the working length (WL) during the root canal treatment. The
      WL is the distance from a coronal reference point to the point at which canal
      preparation and filling should terminate. The "ratio method" was assessed by many
      clinicians with the aim of determining its ability to locate the apical foramen
      (AF). Nevertheless, in vivo studies to assess the method itself and to explain
      why the "ratio method" is able to locate the apical foramen and is unable to
      determine intermediate distances were not published so far. METHODS: A developed
      apparatus applies an electrical current signal with constant amplitude of 10
      MUARMS through the endodontic file within the root canal. The applied current
      signal is composed by summing six sine waves, from 250 Hz to 8 kHz. Data were
      acquired with the endodontic file tip at 7 different positions within root
      canals. In the frequency domain the quotients between the amplitude of a
      reference frequency and the amplitudes of the other frequencies components were
      calculated. Twenty one root canals were analyzed in vivo, during the endodontic
      treatment of twelve teeth of different patients, with age between 20 to 55 years.
      RESULTS: For the range of frequencies used in the commercial EFLs and for
      distances ranging from -3 mm to -1 mm of the AF, the impedance of the root canal
      is mainly resistive. However, when the file tip gets closer to AF, the root canal
      electrical impedance starts to change from a mainly resistive to a complex
      impedance. This change in the measured root canal impedance starts when the file
      tip is near -1.0 mm from the AF, getting stronger as the file tip gets closer to
      the AF. This change in the impedance behavior affects the ratio (quotient) of the
      impedance measured at different frequencies. Through graphic analysis it is
      demonstrated why EFLs based on the ratio method are unable to accurately measure
      any distances between - 3.0 and -0.5 mm from the apical foramen. The only
      reliable measurement is the 0 mm distance, which is when the file tip is at the
      AF. CONCLUSIONS: The electrical impedance values of 21 root canals were in vivo
      studied. The results confirm the ability of EFLs that are based on the ratio
      method to accurately locate the AF position and explain why they are unable to
      determine the file tip position along the root canal.

PMID- 20819213
TI  - Validation of extravascular lung water measurement by single transpulmonary
      thermodilution: human autopsy study.
AB  - INTRODUCTION: Gravimetric validation of single-indicator extravascular lung water
      (EVLW) and normal EVLW values has not been well studied in humans thus far. The
      aims of this study were (1) to validate the accuracy of EVLW measurement by
      single transpulmonary thermodilution with postmortem lung weight measurement in
      humans and (2) to define the statistically normal EVLW values. METHODS: We
      evaluated the correlation between pre-mortem EVLW value by single transpulmonary
      thermodilution and post-mortem lung weight from 30 consecutive autopsies
      completed within 48 hours following the final thermodilution measurement. A
      linear regression equation for the correlation was calculated. In order to
      clarify the normal lung weight value by statistical analysis, we conducted a
      literature search and obtained the normal reference ranges for post-mortem lung
      weight. These values were substituted into the equation for the correlation
      between EVLW and lung weight to estimate the normal EVLW values. RESULTS: EVLW
      determined using transpulmonary single thermodilution correlated closely with
      post-mortem lung weight (r = 0.904, P < 0.001). A linear regression equation was
      calculated: EVLW (mL) = 0.56 * lung weight (g) - 58.0. The normal EVLW values
      indexed by predicted body weight were approximately 7.4 +/- 3.3 mL/kg (7.5 +/-
      3.3 mL/kg for males and 7.3 +/- 3.3 mL/kg for females). CONCLUSIONS: A definite
      correlation exists between EVLW measured by the single-indicator transpulmonary
      thermodilution technique and post-mortem lung weight in humans. The normal EVLW
      value is approximately 7.4 +/- 3.3 mL/kg. TRIAL REGISTRATION: UMIN000002780.

PMID- 20819214
TI  - Culicidae diversity, malaria transmission and insecticide resistance alleles in
      malaria vectors in Ouidah-Kpomasse-Tori district from Benin (West Africa): A pre
      intervention study.
AB  - BACKGROUND: To implement an Insecticide Resistance Management (IRM) strategy
      through a randomized controlled trial (phase III), 28 villages were selected in
      southern Benin. No recent entomological data being available in these villages,
      entomological surveys were performed between October 2007 and May 2008, before
      vector control strategies implementation, to establish baseline data. METHODS:
      Mosquitoes were sampled by human landing collection (16 person-nights per village
      per survey per village) during 5 surveys. Mosquitoes were identified
      morphologically and by molecular methods. The Plasmodium falciparum
      circumsporozoite indexes were measured by ELISA, and the entomological
      inoculation rates (EIRs) were calculated. Molecular detection of pyrethroid knock
      down resistance (Kdr) and of insensitive acetylcholinesterase were performed.
      RESULTS: 44,693 mosquitoes belonging to 28 different species were caught from
      October 2007 to May 2008. Among mosquitoes caught, 318 were An. gambiae s.s., 2
      were An. nili, 568 were An. funestus s.s., and one individual was An. leesoni.
      EIR was 2.05 +/- 1.28 infective bites per human per 100 nights on average, of
      which 0.67 +/- 0.60 were from An. funestus and 1.38 +/- 0.94 infective bites were
      from An. gambiae. Important variations were noted between villages considering
      mosquito density and malaria transmission indicating a spatial heterogeneity in
      the study area. The kdr allelic frequency was 28.86% in An. gambiae s.s. on
      average and significantly increases from October 2007 (10.26%) to May 2008
      (33.87%) in M molecular form of An. gambiae s.s. Ace 1 mutation was found in S
      molecular of An. gambiae s.s at a low frequency (< 1%). CONCLUSION: This study
      updates information on mosquito diversity and malaria risk in rural villages from
      south Benin. It showed a high spatial heterogeneity in mosquito distribution and
      malaria transmission and underlines the need of further investigations of
      biological, ecological, and behavioral traits of malaria vectors species and
      forms. This study is a necessary prerequisite to cartography malaria risk and to
      improve vector control operations in southern Benin.

PMID- 20819215
TI  - Mind your hand during the energy crunch: Functional Outcome of Circular Saw Hand
      Injuries.
AB  - BACKGROUND: Although injuries due to circular saws are very common all over the
      world, there is surprisingly little information available about their functional
      outcomes. As the socioeconomic impact of these injuries is immense and determined
      by the casualties' disability and impairment, it is the objective of this study
      to present data on the functional outcome, disability, and impairment of hand
      injuries due to electric circular saws. METHODS: Patients treated from 1999
      through 2007 for circular saw-related hand injuries were contacted and asked for
      clinical follow-up assessment. The clinical follow-up protocol consisted of a
      physical examination and an assessment of static muscle power (grip and pinch
      strength). For assessment of the subjective experience of the patients regarding
      their injury-related disability and impairment, the DASH follow-up questionnaire
      was used. The occupational impact of these injuries was measured by number of
      lost working days. Finally, safety-related behaviour of the patients was
      investigated. RESULTS: 114 Patients were followed-up on average 52 months after
      the injury. Average in-house treatment was 8.8 days. Average time lost from work
      was 14.8 weeks. A significant reduction of static muscle testing parameters
      compared with the uninjured hand was revealed for grip strength, tip pinch, key
      pinch, and palmar pinch. Average DASH score was 17.4 (DASH work 15.8, DASH
      sports/music 17.7). Most patients had more than ten years experience in using
      these power tools. CONCLUSION: The everyday occurrence of circular saw-related
      hand injuries followed by relatively short periods of in-house treatment might
      distort the real dimension of the patients' remaining disability and impairment.
      While the trauma surgeon's view is generally confined to the patients' clinical
      course, the outcome parameters in this follow-up investigation, with loss of
      working time as the key factor, confirm that the whole socioeconomic burden is
      much greater than the direct cost of treatment.

PMID- 20819216
TI  - Demographic and clinical predictors of depressive symptoms among incarcerated
      women.
AB  - BACKGROUND: Imprisonment may lead to the development of mental illness,
      especially depression. This study examines the clinical and sociodemographic
      profiles of imprisoned women, identifies indicative signs of depression, and
      relates these indicators to other variables. METHODS: This study took the form of
      descriptive exploratory research with a psychometric evaluation. A total of 100
      of 300 women in a female penitentiary were interviewed. A questionnaire with
      sociodemographic, clinical and penal situation information was used, along with
      the Beck Depression Inventory. The authors performed bivariate and multivariate
      analysis regarding depression. RESULTS: In all, 82 women presented signs of
      depression (light = 33, mild = 29 and severe = 20). Comorbidities, lack of
      religious practice, absence of visitors and presence of eating disorders were
      risk factors for depression (P = 0.03, 0.03, 0.02, 0.04, and 0.01). Being older
      was a protection factor against severe depression; for women over 30, the risk of
      depression was multiplied by 0.12. The rate of depression among women prisoners
      was high. CONCLUSIONS: Comorbidities, the lack of religious practice, not having
      visitors and eating disorders are significant risk factors for depression, while
      age is a protective factor, among incarcerated women.

PMID- 20819217
TI  - Association of maternal serum concentrations of 2,2', 4,4'5,5'-hexachlorobiphenyl
      (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) levels
      with birth weight, gestational age and preterm births in Inuit and European
      populations.
AB  - BACKGROUND: Epidemiological studies on the association between maternal exposure
      to persistent organic pollutants (POPs) and fetal growth alteration report
      inconsistent findings which weights in favor of additional studies. METHODS:
      Blood samples were collected from interviewed pregnant women in Greenland (572),
      Kharkiv (611) and Warsaw (258) and were analyzed for CB-153 and p,p'-DDE by gas
      chromatography-mass spectrometry. Data on birth weight, gestational age and
      preterm birth were obtained for 1322 singleton live births. We examined the
      association between natural log-transformed serum POPs concentration and birth
      weight and gestational age using multiple linear regression and the association
      with prematurity using logistic regression controlling for potential confounding
      factors. RESULTS: The median serum concentrations of CB-153 and p,p'-DDE were for
      Inuit mothers 105.6 and 298.9, for Kharkiv mothers 27.0 and 645.4 and for Warsaw
      mothers 10.7 and 365.2 ng/g lipids, respectively. Increase in CB-153
      concentration by one unit on the log scale in Inuit mothers serum was associated
      with significant decrease in infant birth weight of -59 g and gestational age by 
      0.2 week. Decreases observed in the cohorts in Kharkiv (-10 g and -0.1 week) and
      in Warsaw (-49 g and -0.2 week) were not statistically significant. Increase in
      p,p'-DDE concentration by one unit on the log scale was associated with a
      statistically significant decrease in infant birth weight of -39.4 g and -104.3 g
      and shortening of gestational age of -0.2 week and -0.6 week in the Inuit and
      Warsaw cohorts, respectively. In the Kharkiv cohort decrease in birth weight (
      30.5 g) was not significant, however a shortening of gestational age of -0.2 week
      per increase in p,p'-DDE concentration by one unit on the log scale was of the
      borderline significance. There was no significant association between CB-153 and
      p,p'-DDE concentrations and risk of preterm birth however, in all cohorts the
      odds ratio was above 1. CONCLUSIONS: In utero exposure to POPs may reduce birth
      weight and gestational age of newborns however, new insights as to why results
      vary across studies were not apparent.

PMID- 20819218
TI  - A yeast's eye view of mammalian reproduction: cross-species gene co-expression in
      meiotic prophase.
AB  - BACKGROUND: Meiotic prophase is a critical stage in sexual reproduction. Aberrant
      chromosome recombination during this stage is a leading cause of human
      miscarriages and birth defects. However, due to the experimental intractability
      of mammalian gonads, only a very limited number of meiotic genes have been
      characterized. Here we aim to identify novel meiotic genes important in human
      reproduction through computational mining of cross-species and cross-sex time
      series expression data from budding yeast, mouse postnatal testis, mouse
      embryonic ovary, and human fetal ovary. RESULTS: Orthologous gene pairs were
      ranked by order statistics according to their co-expression profiles across
      species, allowing us to infer conserved meiotic genes despite obvious differences
      in cellular synchronicity and composition in organisms. We demonstrated that
      conserved co-expression networks could successfully recover known meiotic genes,
      including homologous recombination genes, chromatin cohesion genes, and genes
      regulating meiotic entry. We also showed that conserved co-expression pairs
      exhibit functional connections, as evidenced by the annotation similarity in Gene
      Ontology and overlap with physical interactions. More importantly, we predicted
      six new meiotic genes through their co-expression linkages with known meiotic
      genes, and subsequently used the genetically more amenable yeast system for
      experimental validation. The deletion mutants of all six genes showed sporulation
      defects, equivalent to a 100% validation rate. CONCLUSIONS: We identified
      evolutionarily conserved gene modules in meiotic prophase by integrating cross
      species and cross-sex expression profiles from budding yeast, mouse, and human.
      Our co-expression linkage analyses confirmed known meiotic genes and identified
      several novel genes that might be critical players in meiosis in multiple
      species. These results demonstrate that our approach is highly efficient to
      discover evolutionarily conserved novel meiotic genes, and yeast can serve as a
      valuable model system for investigating mammalian meiotic prophase.

PMID- 20819219
TI  - The European multicenter trial on the safety and efficacy of guided oblique
      lumbar interbody fusion (GO-LIF).
AB  - BACKGROUND: Because of the implant-related problems with pedicle screw-based
      spinal instrumentations, other types of fixation have been tried in spinal
      arthrodesis. One such technique is the direct trans-pedicular, trans-discal screw
      fixation, pioneered by Grob for spondylolisthesis. The newly developed GO-LIF
      procedure expands the scope of the Grob technique in several important ways and
      adds security by means of robotic-assisted navigation. This is the first clinical
      trial on the GO-LIF procedure and it will assess safety and efficacy.
      METHODS/DESIGN: Multicentric prospective study with n = 40 patients to undergo
      single level instrumented spinal arthrodesis of the lumbar or the lumbosacral
      spine, based on a diagnosis of: painful disc degeneration, painful erosive
      osteochondrosis, segmental instability, recurrent disc herniation, spinal canal
      stenosis or foraminal stenosis. The primary target criteria with regards to
      safety are: The number, severity and cause of intra- and perioperative
      complications. The number of significant penetrations of the cortical layer of
      the vertebral body by the implant as recognized on postoperative CT. The primary
      target parameters with regards to feasibility are: Performance of the procedure
      according to the preoperative plan. The planned follow-up is 12 months and the
      following scores will be evaluated as secondary target parameters with regards to
      clinical improvement: VAS back pain, VAS leg pain, Oswestry Disability Index,
      short form - 12 health questionnaire and the Swiss spinal stenosis questionnaire
      for patients with spinal claudication. The secondary parameters with regards to
      construct stability are visible fusion or lack thereof and signs of implant
      loosening, implant migration or pseudarthrosis on plain and functional
      radiographs. DISCUSSION: This trial will for the first time assess the safety and
      efficacy of guided oblique lumbar interbody fusion. There is no control group,
      but the results, the outcome and the rate of any complications will be analyzed
      on the background of the literature on instrumented spinal fusion. Despite its
      limitations, we expect that this study will serve as the key step in deciding
      whether a direct comparative trial with another fusion technique is warranted.
      TRIAL REGISTRATION: Clinical Trials NCT00810433.

PMID- 20819220
TI  - Randomized phase II study evaluating a carbon ion boost applied after combined
      radiochemotherapy with temozolomide versus a proton boost after radiochemotherapy
      with temozolomide in patients with primary glioblastoma: the CLEOPATRA trial.
AB  - BACKGROUND: Treatment standard for patients with primary glioblastoma (GBM) is
      combined radiochemotherapy with temozolomide (TMZ). Radiation is delivered up to
      a total dose of 60 Gy using photons. Using this treatment regimen, overall
      survival could be extended significantly however, median overall survival is
      still only about 15 months. Carbon ions offer physical and biological advantages.
      Due to their inverted dose profile and the high local dose deposition within the
      Bragg peak precise dose application and sparing of normal tissue is possible.
      Moreover, in comparison to photons, carbon ions offer an increase relative
      biological effectiveness (RBE), which can be calculated between 2 and 5 depending
      on the GBM cell line as well as the endpoint analyzed. Protons, however, offer an
      RBE which is comparable to photons. First Japanese Data on the evaluation of
      carbon ion radiation therapy showed promising results in a small and
      heterogeneous patient collective. METHODS/DESIGN: In the current Phase II
      CLEOPATRA-Study a carbon ion boost will be compared to a proton boost applied to
      the macroscopic tumor after surgery at primary diagnosis in patients with GBM
      applied after standard radiochemotherapy with TMZ up to 50 Gy. In the
      experimental arm, a carbon ion boost will be applied to the macroscopic tumor up
      to a total dose of 18 Gy E in 6 fractions at a single dose of 3 Gy E. In the
      standard arm, a proton boost will be applied up to a total dose 10 Gy E in 5
      single fractions of 2 Gy E. Primary endpoint is overall survival, secondary
      objectives are progression-free survival, toxicity and safety. DISCUSSION: The
      Cleopatra Trial is the first study to evaluate the effect of carbon ion
      radiotherapy within multimodality treatment of primary glioblastoma in a
      randomized trial comparing this innovative treatment of the treatment standard,
      consisitng of photon radiotherapy in combination with temozolomide. TRIAL
      REGISTRATION: ISRCTN37428883 and NCT01165671.

PMID- 20819221
TI  - Increased expression and local accumulation of the prion protein, Alzheimer Abeta
      peptides, superoxide dismutase 1, and nitric oxide synthases 1 & 2 in muscle in a
      rabbit model of diabetes.
AB  - BACKGROUND: Muscle disease associated with different etiologies has been shown to
      produce localized accumulations of amyloid and oxidative stress-related proteins
      that are more commonly associated with neurodegeneration in the brain. In this
      study we examined changes in muscle tissue in a classic model of diabetes and
      hyperglycemia in rabbits to determine if similar dysregulation of Alzheimer Abeta
      peptides, the prion protein (PrP), and superoxide dismutase 1 (SOD1), as well as
      nitric oxide synthases is produced in muscle in diabetic animals. This wild-type
      rabbit model includes systemic physiological expression of human-like Alzheimer
      precursor proteins and Abeta peptides that are considered key in Alzheimer
      protein studies. RESULTS: Diabetes was produced in rabbits by injection of the
      toxic glucose analogue alloxan, which selectively enters pancreatic beta cells
      and irreversibly decreases insulin production, similar to streptozotocin.
      Quadriceps muscle from rabbits 16 wks after onset of diabetes and hyperglycemia
      were analyzed with biochemical and in situ methods. Immunoblots of whole muscle
      protein samples demonstrated increased PrP, SOD1, as well as neuronal and
      inducible Nitric oxide synthases (NOS1 and NOS2) in diabetic muscle. In contrast,
      we detected little change in Alzheimer Abeta precursor protein expression, or
      BACE1 and Presenilin 1 levels. However, Abeta peptides measured by ELISA
      increased several fold in diabetic muscle, suggesting a key role for Abeta
      cleavage in muscle similar to Alzheimer neurodegeneration in this diabetes model.
      Histological changes in diabetic muscle included localized accumulations of PrP,
      Abeta, NOS1 and 2, and SOD1, and evidence of increased central nuclei and cell
      infiltration. CONCLUSIONS: The present study provides evidence that several
      classic amyloid and oxidative stress-related disease proteins coordinately
      increase in overall expression and form localized accumulations in diabetic
      muscle. The present study highlights the capacity of this wild-type animal model
      to produce an array of hallmark pathological features that have also been
      described in other muscle diseases.

PMID- 20819222
TI  - Study protocol: Cost effectiveness of two strategies to implement the NVOG
      guidelines on hypertension in pregnancy: An innovative strategy including a
      computerised decision support system compared to a common strategy of
      professional audit and feedback, a randomized controlled trial.
AB  - BACKGROUND: Hypertensive disease in pregnancy remains the leading cause of
      maternal mortality in the Netherlands. Seventeen percent of the clinical
      pregnancies are complicated by hypertension and 2% by preeclampsia. The Dutch
      Society of Obstetrics and Gynaecology (NVOG) has developed evidence-based
      guidelines on the management of hypertension in pregnancy and chronic
      hypertension. Previous studies showed a low adherence rate to other NVOG
      guidelines and a large variation in usual care in the different hospitals. An
      explanation is that the NVOG has no general strategy of practical implementation
      and evaluation of its guidelines. The development of an effective and cost
      effective implementation strategy to improve adherence to the guidelines on
      hypertension in pregnancy is needed. METHODS/DESIGN: The objective of this study
      is to assess the cost effectiveness of an innovative implementation strategy of
      the NVOG guidelines on hypertension including a computerised decision support
      system (BOS) compared to a common strategy of professional audit and feedback. A
      cluster randomised controlled trial with an economic evaluation alongside will be
      performed. Both pregnant women who develop severe hypertension or pre-eclampsia
      and professionals involved in the care for these women will participate. The main
      outcome measures are a combined rate of major maternal complications and process
      indicators extracted from the guidelines. A total of 472 patients will be
      included in both groups. For analysis, descriptive as well as regression
      techniques will be used. A cost effectiveness and cost utility analysis will be
      performed according to the intention-to-treat principle and from a societal
      perspective. Cost effectiveness ratios will be calculated using bootstrapping
      techniques.

PMID- 20819223
TI  - Manipulative therapy in addition to usual medical care accelerates recovery of
      shoulder complaints at higher costs: economic outcomes of a randomized trial.
AB  - BACKGROUND: Shoulder complaints are common in primary care and have unfavourable
      long term prognosis. Our objective was to evaluate the clinical effectiveness of
      manipulative therapy of the cervicothoracic spine and the adjacent ribs in
      addition to usual medical care (UMC) by the general practitioner in the treatment
      of shoulder complaints. METHODS: This economic evaluation was conducted alongside
      a randomized trial in primary care. Included were 150 patients with shoulder
      complaints and a dysfunction of the cervicothoracic spine and adjacent ribs.
      Patients were treated with UMC (NSAID's, corticosteroid injection or referral to
      physical therapy) and were allocated at random (yes/no) to manipulative therapy
      (manipulation and mobilization). Patient perceived recovery, severity of main
      complaint, shoulder pain, disability and general health were outcome measures.
      Data about direct and indirect costs were collected by means of a cost diary.
      RESULTS: Manipulative therapy as add-on to UMC accelerated recovery on all
      outcome measures included. At 26 weeks after randomization, both groups reported
      similar recovery rates (41% vs. 38%), but the difference between groups in
      improvement of severity of the main complaint, shoulder pain and disability
      sustained. Compared to the UMC group the total costs were higher in the
      manipulative group (?1167 vs. ?555). This is explained mainly by the costs of the
      manipulative therapy itself and the higher costs due sick leave from work. The
      cost effectiveness ratio showed that additional manipulative treatment is more
      costly but also more effective than UMC alone. The cost-effectiveness
      acceptability curve shows that a 50%-probability of recovery with AMT within 6
      months after initiation of treatment is achieved at ?2876. CONCLUSION:
      Manipulative therapy in addition to UMC accelerates recovery and is more
      effective than UMC alone on the long term, but is associated with higher costs.
      INTERNATIONAL STANDARD RANDOMIZED CONTROLLED TRIAL NUMBER REGISTER: ISRCTN11216.

PMID- 20819224
TI  - Does improved access to diagnostic imaging results reduce hospital length of
      stay? A retrospective study.
AB  - BACKGROUND: One year after the introduction of Information and Communication
      Technology (ICT) to support diagnostic imaging at our hospital, clinicians had
      faster and better access to radiology reports and images; direct access to
      Computed Tomography (CT) reports in the Electronic Medical Record (EMR) was
      particularly popular. The objective of this study was to determine whether
      improvements in radiology reporting and clinical access to diagnostic imaging
      information one year after the ICT introduction were associated with a reduction
      in the length of patients' hospital stays (LOS). METHODS: Data describing
      hospital stays and diagnostic imaging were collected retrospectively from the EMR
      during periods of equal duration before and one year after the introduction of
      ICT. The post-ICT period was chosen because of the documented improvement in
      clinical access to radiology results during that period. The data set was
      randomly split into an exploratory part used to establish the hypotheses, and a
      confirmatory part. The data was used to compare the pre-ICT and post-ICT status,
      but also to compare differences between groups. RESULTS: There was no general
      reduction in LOS one year after ICT introduction. However, there was a 25%
      reduction for one group - patients with CT scans. This group was heterogeneous,
      covering 445 different primary discharge diagnoses. Analyses of subgroups were
      performed to reduce the impact of this divergence. CONCLUSION: Our results did
      not indicate that improved access to radiology results reduced the patients' LOS.
      There was, however, a significant reduction in LOS for patients undergoing CT
      scans. Given the clinicians' interest in CT reports and the results of the
      subgroup analyses, it is likely that improved access to CT reports contributed to
      this reduction.

PMID- 20819225
TI  - omega-3 Polyunsaturated fatty acids prevent pressure overload-induced ventricular
      dilation and decrease in mitochondrial enzymes despite no change in adiponectin.
AB  - BACKGROUND: Pathological left ventricular (LV) hypertrophy frequently progresses
      to dilated heart failure with suppressed mitochondrial oxidative capacity.
      Dietary marine omega-3 polyunsaturated fatty acids (omega-3 PUFA) up-regulate
      adiponectin and prevent LV dilation in rats subjected to pressure overload. This
      study 1) assessed the effects of omega-3 PUFA on LV dilation and down-regulation
      of mitochondrial enzymes in response to pressure overload; and 2) evaluated the
      role of adiponectin in mediating the effects of omega-3 PUFA in heart. METHODS:
      Wild type (WT) and adiponectin-/- mice underwent transverse aortic constriction
      (TAC) and were fed standard chow +/- omega-3 PUFA for 6 weeks. At 6 weeks,
      echocardiography was performed to assess LV function, mice were terminated, and
      mitochondrial enzyme activities were evaluated. RESULTS: TAC induced similar
      pathological LV hypertrophy compared to sham mice in both strains on both diets.
      In WT mice TAC increased LV systolic and diastolic volumes and reduced
      mitochondrial enzyme activities, which were attenuated by omega-3 PUFA without
      increasing adiponectin. In contrast, adiponectin-/- mice displayed no increase in
      LV end diastolic and systolic volumes or decrease in mitochondrial enzymes with
      TAC, and did not respond to omega-3 PUFA. CONCLUSION: These findings suggest
      omega-3 PUFA attenuates cardiac pathology in response to pressure overload
      independent of an elevation in adiponectin.

PMID- 20819226
TI  - Profile of blood cells and inflammatory mediators in periodic fever, aphthous
      stomatitis, pharyngitis and adenitis (PFAPA) syndrome.
AB  - BACKGROUND: This study aimed to profile levels of blood cells and serum cytokines
      during afebrile and febrile phases of periodic fever, aphthous stomatitis,
      pharyngitis and adenitis (PFAPA) syndrome to advance pathophysiological
      understanding of this pediatric disease. METHODS: A cohort of patients with a
      median age of 4.9 years experiencing 'typical PFAPA' episodes participated in
      this study. Blood cells and serum cytokines were analyzed by CBC analysis and
      multiplex ELISA. RESULTS: Oscillations in the concentration of blood cells during
      the afebrile and febrile phases of typical PFAPA syndrome were observed; novel
      findings include increased monocytes and decreased eosinophils during a febrile
      episode and increased thrombocytes in the afebrile interval. Relatively modest
      levels of pro-inflammatory cytokines were present in sera. IFNgamma-induced
      cytokine IP10/CXCL10 was increased after the onset of fever while T cell
      associated cytokines IL7 and IL17 were suppressed during afebrile and febrile
      periods. CONCLUSIONS: Identification of dysregulated blood cells and serum
      cytokines is an initial step towards the identification of biomarkers of PFAPA
      disease and/or players in disease pathogenesis. Future investigations are
      required to conclusively discern which mediators are associated specifically with
      PFAPA syndrome.

PMID- 20819228
TI  - Presentations of perforated colonic pathology in patients with polymyalgia
      rheumatica: two case reports.
AB  - INTRODUCTION: Polymyalgia rheumatica is an increasingly common disease in older
      people, which gives rise to arthralgia and is mainly treated with
      corticosteroids. Patients in this age group also have a higher incidence of other
      co-morbidities including colonic pathology. Corticosteroid usage may mask signs
      of sepsis or complications secondary to intra-abdominal pathology, thereby
      delaying diagnosis and treatment, with eventual adverse outcome. These two cases
      highlight the importance of awareness and prompt recognition of this condition in
      order to avoid significant morbidity and mortality. CASE PRESENTATION: CASE 1: A
      73-year-old Caucasian woman with a diagnosis of polymyalgia presented with
      symptoms of an exacerbation in her right hip joint. Despite standard therapy with
      corticosteroids she failed to improve and started to develop features of
      widespread sepsis. Specific questioning revealed that, at the very onset of her
      symptoms, she had experienced mild diarrheal symptoms. Investigations revealed
      perforated diverticular disease with a peri-femoral abscess. CASE 2: A 69-year
      old Caucasian woman with polymyalgia presented with left thigh pain and weakness
      associated with weight loss. A diagnosis of exacerbation of polymyalgia
      rheumatica was made and she was treated with corticosteroid therapy. Shortly
      afterwards she was admitted with generalized peritonitis. Laparotomy revealed a
      retroperitoneal abscess secondary to a perforated sigmoid colonic tumor.
      CONCLUSIONS: Patients with polymyalgia may have perforated colonic diverticular
      disease which mimics their rheumatic pathology. In such cases steroid therapy,
      which is the mainstay of polymyalgia therapy, can be detrimental. Primary and
      hospital practitioners are encouraged to be vigilant regarding non-specific
      gastrointestinal symptoms and consider alternative diagnoses in those patients
      whose symptoms do not resolve with standard therapy, as this can lead to an
      overall better outcome.

PMID- 20819227
TI  - Identification and analysis of candidate fungal tRNA 3'-end processing
      endonucleases tRNase Zs, homologs of the putative prostate cancer susceptibility
      protein ELAC2.
AB  - BACKGROUND: tRNase Z is the endonuclease that is responsible for the 3'-end
      processing of tRNA precursors, a process essential for tRNA 3'-CCA addition and
      subsequent tRNA aminoacylation. Based on their sizes, tRNase Zs can be divided
      into the long (tRNase ZL) and short (tRNase ZS) forms. tRNase ZL is thought to
      have arisen from a tandem gene duplication of tRNase ZS with further sequence
      divergence. The species distribution of tRNase Z is complex. Fungi represent an
      evolutionarily diverse group of eukaryotes. The recent proliferation of fungal
      genome sequences provides an opportunity to explore the structural and functional
      diversity of eukaryotic tRNase Zs. RESULTS: We report a survey and analysis of
      candidate tRNase Zs in 84 completed fungal genomes, spanning a broad diversity of
      fungi. We find that tRNase ZL is present in all fungi we have examined, whereas
      tRNase ZS exists only in the fungal phyla Basidiomycota, Chytridiomycota and
      Zygomycota. Furthermore, we find that unlike the Pezizomycotina and
      Saccharomycotina, which contain a single tRNase ZL, Schizosaccharomyces fission
      yeasts (Taphrinomycotina) contain two tRNase ZLs encoded by two different tRNase
      ZL genes. These two tRNase ZLs are most likely localized to the nucleus and
      mitochondria, respectively, suggesting partitioning of tRNase Z function between
      two different tRNase ZLs in fission yeasts. The fungal tRNase Z phylogeny
      suggests that tRNase ZSs are ancestral to tRNase ZLs. Additionally, the
      evolutionary relationship of fungal tRNase ZLs is generally consistent with known
      phylogenetic relationships among the fungal species and supports tRNase ZL gene
      duplication in certain fungal taxa, including Schizosaccharomyces fission yeasts.
      Analysis of tRNase Z protein sequences reveals putative atypical substrate
      binding domains in most fungal tRNase ZSs and in a subset of fungal tRNase ZLs.
      Finally, we demonstrate the presence of pseudo-substrate recognition and
      catalytic motifs at the N-terminal halves of tRNase ZLs. CONCLUSIONS: This study
      describes the first comprehensive identification and sequence analysis of
      candidate fungal tRNase Zs. Our results support the proposal that tRNase ZL has
      evolved as a result of duplication and diversification of the tRNase ZS gene.

PMID- 20819229
TI  - Molluscicidal efficacies of different formulations of niclosamide: result of meta
      analysis of Chinese literature.
AB  - The control efforts on Oncomelania hupensis, the intermediate snail host of
      Schistosoma japonicum, cannot be easily excluded from the integrated approach of
      schistosomiasis control in China. Application of chemical compounds,
      molluscicides, in snail habitats is a common method for snail control in addition
      to environmental modification. We conducted a systematic review and meta-analysis
      to assess the molluscicidal effects of the currently recommended 50% niclosamide
      ethanolamine salt wettable powder and a new 4% niclosamide ethanolamine salt
      powder developed by Chinese researchers. Literature was searched from three
      Chinese databases, i.e. Chinese Biomedical Database, VIP Database and Wanfang
      Database, on field mollusciciding trials of niclosamide in China (from January 1,
      1990 to April 1, 2010). Molluscicidal effects on reduction of snail population of
      the 50% or 4% niclosamide formulations in field trial were evaluated 3 days, 7
      days or 15 days post-application. Out of 90 publications, 20 papers were
      eventually selected for analysis. Publication bias and heterogeneity tests
      indicated that no publication bias existed but heterogeneity between studies was
      present. Meta-analysis in a random effect model showed that the snail mortality
      of 3, 7 and 15 days after spraying the 50% niclosamide ethanolamine salt wettable
      powder were 77% [95%CI: 0.68-0.86], 83% [95%CI: 0.77-0.89], and 88% [95%CI: 0.82
      0.92], respectively. For the 4% niclosamide ethanolamine salt powder, the snail
      mortality after 3, 7 and 15 days were 81% [95%CI: 0.65-0.93], 90% [95%CI: 0.83
      0.95] and 94% [95%CI: 0.91-0.97], respectively. Both are good enough to be used
      as molluscicides integrated with a schistosomiasis control programme. The 4%
      niclosamide ethanolamine salt powder can be applied in the field without water
      supply as the surrogate of the current widely used 50% niclosamide ethanolamine
      salt wettable powder. However, to consolidate the schistosomiasis control
      achievement gained, it is necessary to continuously perform mollusciciding more
      than twice annually in the field.

PMID- 20819230
TI  - Molecular analysis of the diversity of vaginal microbiota associated with
      bacterial vaginosis.
AB  - BACKGROUND: Bacterial vaginosis (BV) is an ecological disorder of the vaginal
      microbiota that affects millions of women annually, and is associated with
      numerous adverse health outcomes including pre-term birth and the acquisition of
      sexually transmitted infections. However, little is known about the overall
      structure and composition of vaginal microbial communities; most of the earlier
      studies focused on predominant vaginal bacteria in the process of BV. In the
      present study, the diversity and richness of vaginal microbiota in 50 BV positive
      and 50 healthy women from China were investigated using culture-independent PCR
      denaturing gradient gel electrophoresis (DGGE) and barcoded 454 pyrosequencing
      methods, and validated by quantitative PCR. RESULTS: Our data demonstrated that
      there was a profound shift in the absolute and relative abundances of bacterial
      species present in the vagina when comparing populations associated with healthy
      and diseased conditions. In spite of significant interpersonal variations, the
      diversity of vaginal microbiota in the two groups could be clearly divided into
      two clusters. A total of 246,359 high quality pyrosequencing reads was obtained
      for evaluating bacterial diversity and 24,298 unique sequences represented all
      phylotypes. The most predominant phyla of bacteria identified in the vagina
      belonged to Firmicutes, Bacteroidetes, Actinobacteria and Fusobacteria. The
      higher number of phylotypes in BV positive women over healthy is consistent with
      the results of previous studies and a large number of low-abundance taxa which
      were missed in previous studies were revealed. Although no single bacterium could
      be identified as a specific marker for healthy over diseased conditions, three
      phyla - Bacteroidetes, Actinobacteria and Fusobacteria, and eight genera
      including Gardnerella, Atopobium, Megasphaera, Eggerthella, Aerococcus,
      Leptotrichia/Sneathia, Prevotella and Papillibacter were strongly associated with
      BV (p < 0.05). These genera are potentially excellent markers and could be used
      as targets for clinical BV diagnosis by molecular approaches. CONCLUSIONS: The
      data presented here have clearly profiled the overall structure of vaginal
      communities and clearly demonstrated that BV is associated with a dramatic
      increase in the taxonomic richness and diversity of vaginal microbiota. The study
      also provides the most comprehensive picture of the vaginal community structure
      and the bacterial ecosystem, and significantly contributes to the current
      understanding of the etiology of BV.

PMID- 20819231
TI  - Internal mammary lymph node recurrence: rare but characteristic metastasis site
      in breast cancer.
AB  - BACKGROUND: To assess the frequency of IMLN recurrence, its associated risk
      factors with disease-free interval (DFI) and its predicting factors on overall
      survival time. METHODS: 133 cases of breast cancer IMLN recurrence were
      identified via the computerized CT reporting system between February 2003 and
      June 2008, during which chest CT for patients with breast cancer (n = 8867) were
      performed consecutively at Cancer Hospital, Fudan University, Shanghai, China.
      Patients' charts were retrieved and patients' characteristics, disease
      characteristics, and treatments after recurrence were collected for analysis. The
      frequency was 1.5% (133/8867). RESULTS: IMLN recurrence was presented as the
      first metastatic site in 121 (91%) patients while 88 (66.2%) had other concurrent
      metastases. Typical chest CT images included swelling of the IMLN at the
      ipsilateral side with local lump and sternal erosion located mostly between the
      second and third intercostal space. The median disease-free interval (DFI) of
      IMLN recurrence was 38 months. The independent factors that could delay the IMLN
      recurrence were small tumor size (HR 0.5 95%CI: 0.4 - 0.8; p = 0.002), and
      positive ER/PR disease (HR 0.6, 95% CI: 0.4 - 0.9; p = 0.006). The median
      survival time after IMLN recurrence was 42 months, with a 5-year survival rate of
      30%. Univariate analysis showed four variables significantly influenced the
      survival time: DFI of IMLN recurrence (p = 0.001), no concurrent distant
      metastasis (p = 0.024), endocrine therapy for patients with positive ER/PR (p =
      0.000), radiotherapy (p = 0.040). The independent factors that reduced the death
      risk were no concurrent distant metastases (HR: 0.7, 95% CI: 0.4 - 0.9; p =
      0.031), endocrine therapy for patients with positive ER/PR status (HR: 0.2, 95%
      CI: 0.1 - 0.5; p = 0.001) and palliative radiotherapy (HR: 0.3, 95% CI: 0.1- 0.9;
      p = 0.026). CONCLUSIONS: The risk of IMLN recurrence is low and there are certain
      characteristics features on CT images. ER/PR status is both a risk factor for DFI
      of IMLN recurrence and a prognostic factor for overall survival after IMLN
      recurrence. Patients with only IMLN recurrence and/or local lesion have a good
      prognosis.

PMID- 20819232
TI  - Upregulation of a novel eukaryotic translation initiation factor 5A (eIF5A) in
      dengue 2 virus-infected mosquito cells.
AB  - BACKGROUND: Dengue virus, a mosquito-borne flavivirus, is the etiological agent
      of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. It
      generally induces apoptosis in mammalian cells, but frequently results in
      persistent infection in mosquito cells. That mechanism remains to be explored. In
      turn, a genomic survey through subtractive hybridization (PCR-select cDNA
      subtraction) was conducted in order to find gene(s) that may play a role in
      interactions between the virus and its host cells. RESULTS: Through this
      technique, we identified a novel eukaryotic translation initiation factor 5A
      (eIF5A) which is upregulated in Aedes albopictus-derived C6/36 cells infected by
      the type 2 dengue (Den-2) virus. The full-length of the identified eIF5A gene
      consisted of 1498 bp of nucleotides with a 41.39% G+C content, and it possessed a
      higher similarity and shorter evolutionary distance with insects than with other
      organisms. Upregulation of eIF5A in response to Den-2 virus infection was
      validated at both the RNA and protein levels. This phenomenon was also observed
      by confocal microscopy. In addition, cell death obviously occurred when eIF5A
      activity was inhibited in C6/36 cells even when they were infected by the virus.
      However, viral multiplication was not obviously affected in infected C6/36 cells
      when eIF5A activity was reduced. CONCLUSIONS: Taken together, we postulated that
      eIF5A plays a role in preventing mosquito cells from death in response to Den-2
      viral infection, thus facilitating continued viral growth and potential
      persistent infection in mosquito cells. It would be worthwhile to further
      investigate how its downstream factors or cofactors contribute to this phenomenon
      of dengue infection.

PMID- 20819233
TI  - Consistency, comprehensiveness, and compatibility of pathway databases.
AB  - BACKGROUND: It is necessary to analyze microarray experiments together with
      biological information to make better biological inferences. We investigate the
      adequacy of current biological databases to address this need. DESCRIPTION: Our
      results show a low level of consistency, comprehensiveness and compatibility
      among three popular pathway databases (KEGG, Ingenuity and Wikipathways). The
      level of consistency for genes in similar pathways across databases ranges from
      0% to 88%. The corresponding level of consistency for interacting genes pairs is
      0%-61%. These three original sources can be assumed to be reliable in the sense
      that the interacting gene pairs reported in them are correct because they are
      curated. However, the lack of concordance between these databases suggests each
      source has missed out many genes and interacting gene pairs. CONCLUSIONS:
      Researchers will hence find it challenging to obtain consistent pathway
      information out of these diverse data sources. It is therefore critical to enable
      them to access these sources via a consistent, comprehensive and unified pathway
      API. We accumulated sufficient data to create such an aggregated resource with
      the convenience of an API to access its information. This unified resource can be
      accessed at http://www.pathwayapi.com.

PMID- 20819234
TI  - Heme oxygenase-1 plays a pro-life role in experimental brain stem death via
      nitric oxide synthase I/protein kinase G signaling at rostral ventrolateral
      medulla.
AB  - BACKGROUND: Despite its clinical importance, a dearth of information exists on
      the cellular and molecular mechanisms that underpin brain stem death. A suitable
      neural substrate for mechanistic delineation on brain stem death resides in the
      rostral ventrolateral medulla (RVLM) because it is the origin of a life-and-death
      signal that sequentially increases (pro-life) and decreases (pro-death) to
      reflect the advancing central cardiovascular regulatory dysfunction during the
      progression towards brain stem death in critically ill patients. The present
      study evaluated the hypothesis that heme oxygnase-1 (HO-1) may play a pro-life
      role as an interposing signal between hypoxia-inducible factor-1 (HIF-1) and
      nitric oxide synthase I (NOS I)/protein kinase G (PKG) cascade in RVLM, which
      sustains central cardiovascular regulatory functions during brain stem death.
      METHODS: We performed cardiovascular, pharmacological, biochemical and confocal
      microscopy experiments in conjunction with an experimental model of brain stem
      death that employed microinjection of the organophosphate insecticide mevinphos
      (Mev; 10 nmol) bilaterally into RVLM of adult male Sprague-Dawley rats. RESULTS:
      Western blot analysis coupled with laser scanning confocal microscopy revealed
      that augmented HO-1 expression that was confined to the cytoplasm of RVLM neurons
      occurred preferentially during the pro-life phase of experimental brain stem
      death and was antagonized by immunoneutralization of HIF-1alpha or HIF-1beta in
      RVLM. On the other hand, the cytoplasmic presence of HO-2 in RVLM neurons
      manifested insignificant changes during both phases. Furthermore,
      immunoneutralization of HO-1 or knockdown of ho-1 gene in RVLM blunted the
      augmented life-and-death signals exhibited during the pro-life phase. Those
      pretreatments also blocked the upregulated pro-life NOS I/PKG signaling without
      affecting the pro-death NOS II/peroxynitrite cascade in RVLM. CONCLUSIONS: We
      conclude that transcriptional upregulation of HO-1 on activation by HIF-1 in RVLM
      plays a preferential pro-life role by sustaining central cardiovascular
      regulatory functions during brain stem death via upregulation of NOS I/PKG
      signaling pathway. Our results further showed that the pro-dead NOS
      II/peroxynitrite cascade in RVLM is not included in this repertoire of cellular
      events.

PMID- 20819235
TI  - Psychiatric inpatient expenditures and public health insurance programmes:
      analysis of a national database covering the entire South Korean population.
AB  - BACKGROUND: Medical spending on psychiatric hospitalization has been reported to
      impose a tremendous socio-economic burden on many developed countries with public
      health insurance programmes. However, there has been no in-depth study of the
      factors affecting psychiatric inpatient medical expenditures and differentiated
      these factors across different types of public health insurance programmes. In
      view of this, this study attempted to explore factors affecting medical
      expenditures for psychiatric inpatients between two public health insurance
      programmes covering the entire South Korean population: National Health Insurance
      (NHI) and National Medical Care Aid (AID). METHODS: This retrospective, cross
      sectional study used a nationwide, population-based reimbursement claims dataset
      consisting of 1,131,346 claims of all 160,465 citizens institutionalized due to
      psychiatric diagnosis between January 2005 and June 2006 in South Korea. To
      adjust for possible correlation of patients characteristics within the same
      medical institution and a non-linearity structure, a Box-Cox transformed,
      multilevel regression analysis was performed. RESULTS: Compared with inpatients
      19 years old or younger, the medical expenditures of inpatients between 50 and 64
      years old were 10% higher among NHI beneficiaries but 40% higher among AID
      beneficiaries. Males showed higher medical expenditures than did females.
      Expenditures on inpatients with schizophrenia as compared to expenditures on
      those with neurotic disorders were 120% higher among NHI beneficiaries but 83%
      higher among AID beneficiaries. Expenditures on inpatients of psychiatric
      hospitals were greater on average than expenditures on inpatients of general
      hospitals. Among AID beneficiaries, institutions owned by private groups treated
      inpatients with 32% higher costs than did government institutions. Among NHI
      beneficiaries, inpatients medical expenditures were positively associated with
      the proportion of patients diagnosed into dementia or schizophrenia categories.
      However, for AID beneficiaries, inpatient medical expenditures were positively
      associated with the proportion of all patients with a psychiatric diagnosis that
      were AID beneficiaries in a medical institution. CONCLUSIONS: This study provides
      evidence that patient and institutional factors are associated with psychiatric
      inpatient medical expenditures, and that they may have different effects for
      beneficiaries of different public health insurance programmes. Policy efforts to
      reduce psychiatric inpatient medical expenditures should be made differently
      across the different types of public health insurance programmes.

PMID- 20819236
TI  - Engaging community pharmacists in the primary prevention of cardiovascular
      disease: protocol for the Pharmacist Assessment of Adherence, Risk and Treatment
      in Cardiovascular Disease (PAART CVD) pilot study.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death globally.
      Community pharmacist intervention studies have demonstrated clinical
      effectiveness for improving several leading individual CVD risk factors. Primary
      prevention strategies increasingly emphasise the need for consideration of
      overall cardiovascular risk and concurrent management of multiple risk factors.
      It is therefore important to demonstrate the feasibility of multiple risk factor
      management by community pharmacists to ensure continued currency of their role.
      METHODS/DESIGN: This study will be a longitudinal pre- and post-test pilot study
      with a single cohort of up to 100 patients in ten pharmacies. Patients aged 50-74
      years with no history of heart disease or diabetes, and taking antihypertensive
      or lipid-lowering medicines, will be approached for participation. Assessment of
      cardiovascular risk, medicines use and health behaviours will be undertaken by a
      research assistant at baseline and following the intervention (6 months).
      Validated interview scales will be used where available. Baseline data will be
      used by accredited medicines management pharmacists to generate a report for the
      treating community pharmacist. This report will highlight individual patients'
      overall CVD risk and individual risk factors, as well as identifying modifiable
      health behaviours for risk improvement and suggesting treatment and behavioural
      goals. The treating community pharmacist will use this information to finalise
      and implement a treatment plan in conjunction with the patient and their doctor.
      Community pharmacists will facilitate patient improvements in lifestyle,
      medicines adherence, and medicines management over the course of five counselling
      sessions with monthly intervals. The primary outcome will be the change to
      average overall cardiovascular risk, assessed using the Framingham risk equation.
      DISCUSSION: This study will assess the feasibility of implementing holistic
      primary CVD prevention programs into community pharmacy, one of the most
      accessible health services in most developed countries. TRIAL REGISTRATION:
      Australia and New Zealand Clinical Trial Registry Number: ACTRN12609000677202.

PMID- 20819237
TI  - Determining and interpreting correlations in lipidomic networks found in
      glioblastoma cells.
AB  - BACKGROUND: Intelligent and multitiered quantitative analysis of biological
      systems rapidly evolves to a key technique in studying biomolecular cancer
      aspects. Newly emerging advances in both measurement as well as bio-inspired
      computational techniques have facilitated the development of lipidomics
      technologies and offer an excellent opportunity to understand regulation at the
      molecular level in many diseases. RESULTS: We present computational approaches to
      study the response of glioblastoma U87 cells to gene- and chemo-therapy. To
      identify distinct biomarkers and differences in therapeutic outcomes, we develop
      a novel technique based on graph-clustering. This technique facilitates the
      exploration and visualization of co-regulations in glioblastoma lipid profiling
      data. We investigate the changes in the correlation networks for different
      therapies and study the success of novel gene therapies targeting aggressive
      glioblastoma. CONCLUSIONS: The novel computational paradigm provides unique
      "fingerprints" by revealing the intricate interactions at the lipidome level in
      glioblastoma U87 cells with induced apoptosis (programmed cell death) and thus
      opens a new window to biomedical frontiers.

PMID- 20819238
TI  - Comparison of participants and non-participants to the ORISCAV-LUX population
      based study on cardiovascular risk factors in Luxembourg.
AB  - BACKGROUND: Poor response is a major concern in public health surveys. In a
      population-based ORISCAV-LUX study carried out in Grand-Duchy of Luxembourg to
      assess the cardiovascular risk factors, the non-response rate was not negligible.
      The aims of the present work were: 1) to investigate the representativeness of
      study sample to the general population, and 2) to compare the known demographic
      and cardiovascular health-related profiles of participants and non-participants.
      METHODS: For sample representativeness, the participants were compared to the
      source population according to stratification criteria (age, sex and district of
      residence). Based on complementary information from the "medical administrative
      database", further analysis was carried out to assess whether the health status
      affected the response rate. Several demographic and morbidity indicators were
      used in the univariate comparison between participants and non-participants.
      RESULTS: Among the 4452 potentially eligible subjects contacted for the study,
      there were finally 1432 (32.2%) participants. Compared to the source population,
      no differences were found for gender and district distribution. By contrast, the
      youngest age group was under-represented while adults and elderly were over
      represented in the sample, for both genders. Globally, the investigated clinical
      profile of the non-participants was similar to that of participants. Hospital
      admission and cardiovascular health-related medical measures were comparable in
      both groups even after controlling for age. The participation rate was lower in
      Portuguese residents as compared to Luxembourgish (OR = 0.58, 95% CI: 0.48-0.69).
      It was also significantly associated with the professional status (P < 0.0001).
      Subjects from the working class were less receptive to the study than those from
      other professional categories. CONCLUSION: The 32.2% participation rate obtained
      in the ORISCAV-LUX survey represents the realistic achievable rate for this type
      of multiple-stage, nationwide, population-based surveys. It corresponds to the
      expected rate upon which the sample size was calculated. Given the absence of
      discriminating health profiles between participants and non-participants, it can
      be concluded that the response rate does not invalidate the results and allows
      generalizing the findings for the population.

PMID- 20819239
TI  - Extracerebral metastases determine the outcome of patients with brain metastases
      from renal cell carcinoma.
AB  - BACKGROUND: In the era of cytokines, patients with brain metastases (BM) from
      renal cell carcinoma had a significantly shorter survival than patients without.
      Targeted agents (TA) have improved the outcome of patients with metastatic renal
      cell carcinoma (mRCC) however, their impact on patients with BM is less clear.
      The aim of this analysis was to compare the outcome of patients with and without
      BM in the era of targeted agents. METHODS: Data from 114 consecutive patients who
      had access to targeted agent were analyzed for response rates (ORR), progression
      free survival (PFS) and overall survival (OS). All patients diagnosed with BM
      underwent local, BM-specific treatment before initiation of medical treatment.
      RESULTS: Data of 114 consecutive patients who had access to at least one type of
      targeted agents were analyzed. Twelve out of 114 renal cell carcinoma (RCC)
      patients (10.5%) were diagnosed with BM. Systemic treatment consisted of
      sunitinib, sorafenib, temsirolimus or bevacizumab. The median PFS was 8.7 months
      (95% CI 5.1 - 12.3) and 11.4 months (95% CI 8.7 - 14.1) for BM-patients and non
      BM-patients, respectively (p = 0.232). The median overall survival for patients
      with and without BM was 13.4 (95% CI 1- 43.9) and 33.3 months (95% CI 18.6 -
      47.0) (p = 0.358), respectively. No patient died from cerebral disease
      progression. ECOG Performance status and the time from primary tumor to
      metastases (TDM) were independent risk factors for short survival (HR 2.74, p =
      0.001; HR: 0.552, p = 0.034). CONCLUSIONS: Although extracerebral metastases
      determine the outcome of patients with BM, the benefit from targeted agents still
      appears to be limited when compared to patients without BM.

PMID- 20819240
TI  - Pharmacokinetics and first-pass metabolism of astaxanthin in rats.
AB  - Astaxanthin is a carotenoid with antioxidant, anti-cancer and anti-inflammatory
      properties. The pharmacokinetics of astaxanthin after its intravenous (5, 10, and
      20 mg/kg) and oral (100 and 200 mg/kg) administration and its first-pass
      extraction ratios after its intravenous, intraportal or intragastric (20 mg/kg)
      administration were evaluated in rats. The pharmacokinetic parameters of
      astaxanthin were dose dependent after its intravenous administration, due to the
      saturable hepatic metabolism of astaxanthin, but dose independent after oral
      administration. The gastrointestinal absorption of astaxanthin followed the flip
      flop model. The hepatic and gastrointestinal first-pass extraction ratios of
      astaxanthin were approximately 0.490 and 0.901, respectively. Astaxanthin was
      metabolised primarily by hepatic cytochrome P-450 1A1/2 in rats. Astaxanthin was
      unstable up to 4 h incubation in four rat gastric juices and up to 24 h
      incubation in various buffer solutions having a pH of 1-13. The tissue/plasma
      ratios of astaxanthin at 8 and 24 h after its oral administration (100 mg/kg)
      were greater than unity for all tissues studied, except in the heart, at 8 h,
      indicating that the rat tissues studied had high affinity for astaxanthin.

PMID- 20819241
TI  - Host-parasite relationships in flatfish (Pleuronectiformes)--the relative
      importance of host biology, ecology and phylogeny.
AB  - The extent to which host biology, ecology and phylogeny determine the diversity
      of macroparasite assemblages has been investigated in recent years in several
      taxa, including fish. However, consensus has not been reached probably as a
      result of data being collected from different sources, different temporal scales
      or host and parasite biogeography and phylogeny having greater influence than
      expected. The present study evaluates the relative importance of 27 biological,
      ecological and phylogenetic characteristics of 14 flatfish species on the
      diversity of their ecto- and endoparasite assemblages, comprising a total of 53
      taxa. Redundancy analyses were applied to the mean abundance of each parasite
      taxa infecting each host and to the richness, taxonomic distinctness and variance
      in taxonomic distinctness calculated for each assemblage within each host. Only a
      few host characteristics contributed significantly to the observed patterns: host
      distribution was more important in determining the type and mean abundance of
      ectoparasites present in an assemblage, whereas diversity of these assemblages
      were mainly related to the host's maximum size. Endoparasite mean abundance and
      diversity were mostly influenced by the number of food items ingested and by the
      presence of Crustacea and Polychaeta in the diet. However, the sympatric
      occurrence of related hosts also played an important role in the diversity values
      found in macroparasite assemblages. Results showed that a host characteristic has
      different importance according to the host-parasite relationship being examined,
      suggesting an important role for host-parasite co-evolution on the diversity of
      extant macroparasite assemblages.

PMID- 20819242
TI  - Protein functional landscapes, dynamics, allostery: a tortuous path towards a
      universal theoretical framework.
AB  - Energy landscape theories have provided a common ground for understanding the
      protein folding problem, which once seemed to be overwhelmingly complicated. At
      the same time, the native state was found to be an ensemble of interconverting
      states with frustration playing a more important role compared to the folding
      problem. The landscape of the folded protein - the native landscape - is glassier
      than the folding landscape; hence, a general description analogous to the folding
      theories is difficult to achieve. On the other hand, the native basin phase
      volume is much smaller, allowing a protein to fully sample its native energy
      landscape on the biological timescales. Current computational resources may also
      be used to perform this sampling for smaller proteins, to build a 'topographical
      map' of the native landscape that can be used for subsequent analysis. Several
      major approaches to representing this topographical map are highlighted in this
      review, including the construction of kinetic networks, hierarchical trees and
      free energy surfaces with subsequent structural and kinetic analyses. In this
      review, we extensively discuss the important question of choosing proper
      collective coordinates characterizing functional motions. In many cases, the
      substates on the native energy landscape, which represent different functional
      states, can be used to obtain variables that are well suited for building free
      energy surfaces and analyzing the protein's functional dynamics. Normal mode
      analysis can provide such variables in cases where functional motions are
      dictated by the molecule's architecture. Principal component analysis is a more
      expensive way of inferring the essential variables from the protein's motions,
      one that requires a long molecular dynamics simulation. Finally, the two popular
      models for the allosteric switching mechanism, 'preexisting equilibrium' and
      'induced fit', are interpreted within the energy landscape paradigm as extreme
      points of a continuum of transition mechanisms. Some experimental evidence
      illustrating each of these two models, as well as intermediate mechanisms, is
      presented and discussed.

PMID- 20819243
TI  - A systematic review of waist-to-height ratio as a screening tool for the
      prediction of cardiovascular disease and diabetes: 0.5 could be a suitable global
      boundary value.
AB  - This systematic review collated seventy-eight studies exploring waist-to-height
      ratio (WHtR) and waist circumference (WC) or BMI as predictors of diabetes and
      CVD, published in English between 1950 and 2008. Twenty-two prospective analyses
      showed that WHtR and WC were significant predictors of these cardiometabolic
      outcomes more often than BMI, with similar OR, sometimes being significant
      predictors after adjustment for BMI. Observations from cross-sectional analyses,
      forty-four in adults, thirteen in children, supported these predictions. Receiver
      operator characteristic (ROC) analysis revealed mean area under ROC (AUROC)
      values of 0.704, 0.693 and 0.671 for WHtR, WC and BMI, respectively. Mean
      boundary values for WHtR, covering all cardiometabolic outcomes, from studies in
      fourteen different countries and including Caucasian, Asian and Central American
      subjects, were 0.50 for men and 0.50 for women. WHtR and WC are therefore similar
      predictors of diabetes and CVD, both being stronger than, and independent of,
      BMI. To make firmer statistical comparison, a meta-analysis is required. The
      AUROC analyses indicate that WHtR may be a more useful global clinical screening
      tool than WC, with a weighted mean boundary value of 0.5, supporting the simple
      public health message 'keep your waist circumference to less than half your
      height'.

PMID- 20819244
TI  - Ready-to-eat cereals and the burden of obesity in the context of their
      nutritional contribution: are all ready-to-eat cereals equally healthy? A
      systematic review.
AB  - A significant increase in the prevalence of obesity has occurred worldwide and
      the importance of considering the role of diet in the prevention and treatment of
      obesity is widely acknowledged. A growing body of evidence encourages the
      consumption of ready-to-eat cereals (RTEC) as part of a healthful diet. Research
      has shown an inverse association between the consumption of RTEC and the rate of
      obesity. However, other findings claim that this association was only attributed
      to the consumption of whole-grain cereals and not the refined-grain ones.
      Although meta-analyses of clinical trials support the use of a low-glycaemic
      index diet on weight loss, findings from other studies on the effect of the
      dietary glycaemic index on body weight have not been consistent. Thus, further
      research into the role of glycaemic index in the prevention and management of
      obesity and chronic disease is needed. Moreover, significant differences have
      been observed in composition among the marketed RTEC. In light of the revealing
      protective role of whole-grain, fibre-rich, low-energy-dense and low-glycaemic
      index/glycaemic load foods against obesity, public health professionals could
      drive their efforts towards the promotion of even more healthier RTEC when
      issuing advice on weight management. It seems, however, that despite any
      differences in their composition, the frequent consumption of RTEC due to their
      nutritional contribution is recommended in moderation and under the current
      recommendations in the context of a healthy balanced diet.

PMID- 20819246
TI  - An assessment of between-recti distance and divarication in patients with and
      without abdominal aortic aneurysm.
AB  - INTRODUCTION: The study assessed whether there is a greater incidence of
      divarication of the recti and whether between-recti distance is greater in
      patients with abdominal aortic aneurysm (AAA). PATIENTS AND METHODS: The study
      consisted of two parts: a radiological and a clinical assessment. All patients
      with a confirmed AAA on computerised tomography were included and compared with
      patients in whom AAA was excluded with imaging. Between-recti distance was
      measured using a computerised image viewer and clinical divarication was assessed
      by a surgical registrar or consultant. RESULTS: In the radiological part of the
      study, 108 patients with AAA were compared with 84 with colorectal cancer. Median
      between-recti distance was 38 mm (range, 25-59 mm) in the AAA group and 27 mm
      (range, 20-44.5 mm) in the non-AAA group (P=0.006). AAA diameter did not
      correlate with between-recti distance. The clinical study included 50 patients
      (25 AAA). The groups were well matched, with only a greater incidence of diabetes
      in the AAA group (20% vs 0%; P=0.018). AAA patients were more likely to have
      clinically detected divarication of the recti (76% vs 36%; P=0.004). CONCLUSIONS:
      Patients with AAA have greater radiological and clinical evidence of
      divarication. It is suggested that patients with divarication be screened for
      AAA.

PMID- 20819247
TI  - Gastrointestinal stromal tumour presenting with duodenal-jejunal intussusception:
      a case report.
AB  - Duodenal-jejunal intussusception is an extremely rare occurrence and has never
      been reported in the context of a gastrointestinal stromal tumour (GIST). We
      present the case of a duodenal GIST which presented with major intestinal
      haemorrhage in addition to duodenal-jejunal intussusception.

PMID- 20819248
TI  - Why has zoonotic tuberculosis not received much attention?

PMID- 20819249
TI  - Tuberculosis in humans and animals: an overview.
AB  - Tuberculosis (TB) is a significant disease for both humans and animals.
      Susceptibility to Mycobacterium tuberculosis is relatively high in humans, other
      primates and guinea pigs. Cattle, rabbits and cats are susceptible to M. bovis
      and are quite resistant to M. tuberculosis. Wild hoofed stock is generally
      susceptible to M. bovis, but few reports are available on the isolation of M.
      tuberculosis. Swine and dogs are susceptible to both M. bovis and M.
      tuberculosis. M. bovis accounts for only a small percentage of the reported cases
      of TB in humans; however, it is a pathogen of significant economic importance in
      wild and domestic animals around the globe, especially in countries where little
      information is available on the incidence of M. bovis infection in humans. Unlike
      transmission of M. bovis from cattle to humans, the role of human-to-human
      airborne transmission in the spread of M. bovis has been somewhat controversial.
      Investigations are needed to elucidate the relative importance of M. bovis on TB
      incidence in humans, especially in developing countries. Efforts should be
      concentrated in countries where human immunodeficiency virus (HIV) infection is
      widespread, as HIV-infected individuals are more susceptible to mycobacterial
      disease. Eradication of M. bovis in cattle and pasteurisation of dairy products
      are the cornerstones of the prevention of human disease.

PMID- 20819250
TI  - Respiratory health effects of indoor air pollution.
AB  - Domestic pollution is relevant to health because people spend most of their time
      indoors. One half of the world's population is exposed to high concentrations of
      solid fuel smoke (biomass and coal) that are produced by inefficient open fires,
      mainly in the rural areas of developing countries. Concentrations of particulate
      matter in kitchens increase to the range of milligrams per cubic meter during
      cooking. Solid fuel smoke possesses the majority of the toxins found in tobacco
      smoke and has also been associated with a variety of diseases, such as chronic
      obstructive pulmonary disease in women, acute respiratory infection in children
      and lung cancer in women (if exposed to coal smoke). Other tobacco smoke
      associated diseases, such as tuberculosis, asthma, respiratory tract cancer and
      interstitial lung diseases, may also be associated with solid fuel smoke
      inhalation, but evidence is limited. As the desirable change to clean fuels is
      unlikely, efforts have been made to use efficient, vented wood or coal stoves,
      with varied success due to inconsistent acceptance by the community.

PMID- 20819251
TI  - Laboratory tests focusing on sputum.

PMID- 20819252
TI  - Surveillance for MDR-TB: is there an obligation to ensure treatment for
      individuals identified with MDR-TB?
AB  - This article raises ethical issues that result if individuals, during the course
      of research to measure the prevalence of drug-resistant tuberculosis, are
      identified with the disease but are not provided with or referred for appropriate
      treatment. It draws attention to and applauds recently published World Health
      Organization guidelines on the subject. Questions posed are: 1) Should treatment
      be provided for individuals identified through surveillance projects for MDR-TB,
      whatever their purpose (specific research or 'routine' national prevalence
      studies)? 2) If treatment availability is a problem, who is responsible for
      assuring this?

PMID- 20819253
TI  - Factors influencing performance of Global Fund-supported tuberculosis grants.
AB  - OBJECTIVE: To explore grant and country characteristics associated with the
      performance of tuberculosis (TB) grants supported by the Global Fund to Fight
      AIDS, Tuberculosis and Malaria (Global Fund), which uses performance-based
      funding of grants. METHODS: We used Global Fund grant data to compute the average
      programmatic performance of 108 TB grants in 88 countries. Using stepwise
      regression models, we examined the correlation of grant performance with a range
      of grant and country characteristics. RESULTS: Funding duration and funding per
      estimated smear-positive TB case were positively correlated with grant
      performance (partial correlations of 0.386-0.416 for the former, 0.200 for the
      latter). Successful completion of an evaluation of a grant during the second year
      of funding was linked to higher performance (0.357). Performance was further
      influenced by the independent organisation hired by the Global Fund to provide
      ongoing monitoring of the grants (0.197-0.243). Two country-specific factors were
      significantly correlated with performance: political stability (0.197-0.234) and
      disease burden (-0.211). DISCUSSION: Successful evaluation that leads to
      continued funding predicts higher performance of TB grants, even in challenging
      settings such as weak health services. However, other contextual factors affect
      grant performance and should be considered when assessing grants to ensure that
      countries that have a high disease burden and are politically unstable are not
      penalized.

PMID- 20819254
TI  - Predictors of latent tuberculosis infection treatment completion in the United
      States: an inner city experience.
AB  - BACKGROUND: Few studies have examined predictors of latent tuberculosis infection
      (LTBI) treatment completion in inner city populations in the United States.
      OBJECTIVE: To assess LTBI treatment completion rates and predictors in an inner
      city cohort. METHODS: Data from control groups of two sequentially conducted
      randomized controlled trials of LTBI treatment were analyzed for treatment
      completion rates. Participants in Study A (n = 191), conducted in 1996-1999, self
      administered daily isoniazid (INH) for 6-12 months, while participants in Study B
      (n = 123), conducted in 2002-2005, self administered daily INH for 9 months.
      RESULTS: Overall, 44.6% of participants completed therapy, with significantly
      higher completion rates in Study B than Study A (37.0% vs. 56.1%, P = 0.001).
      Marriage and alcohol use were significant predictors of completion (aOR = 2.153,
      95%CI 1.301-3.562) and non-completion (aOR = 0.530, 95%CI 0.320-0.877),
      respectively; multivariate analysis indicated increased completion among married
      persons of foreign birth and among alcohol users who were homeless. Knowledge of
      and attitudes to tuberculosis were not significant predictors. CONCLUSIONS: The
      design provided an opportunity to assess predictors of LTBI treatment completion
      in this inner city population. Social circumstances were the strongest predictors
      of treatment completion, suggesting that tangible social services may be more
      effective than educational programs in encouraging treatment completion.

PMID- 20819255
TI  - Risk factors for developing tuberculosis: a 12-year follow-up of contacts of
      tuberculosis cases.
AB  - BACKGROUND: Many risk factors for the development of tuberculosis (TB) have been
      reported but have not been simultaneously assessed. OBJECTIVE: To determine the
      risk of developing TB associated with each risk factor, after adjusting for all
      others. METHODS: We performed a population-based, retrospective cohort study of
      the contacts of TB cases recorded in British Columbia, Canada. Known risk factors
      for the development of TB were assessed over a 12-year period; Cox regression was
      used to estimate the hazard ratios (HRs) of TB, adjusting for the other factors.
      RESULTS: Among 33 146 TB contacts, 228 developed TB during the study period (TB
      rate 668 per 100,000 population, 95%CI 604-783). The main risk factors for TB
      development were malnutrition (HR 37.5), no treatment of latent TB infection (HR
      25) or <6 months of treatment (HR 5.38), age 0-10 years (HR 7.87), being a
      household contact (HR 8.47) and having a tuberculin skin test induration of >or=5
      mm (HR >or=4.99). Bacille Calmette-Guerin vaccination significantly reduced the
      risk of TB development (HR 0.32, 95%CI 0.20-0.50). CONCLUSIONS: Among contacts of
      TB cases, we have identified the few factors that carry a very high risk for
      developing TB. These factors identify populations at highest risk and permit more
      effective TB control.

PMID- 20819256
TI  - Tuberculosis transmission risk and infection control in a hospital emergency
      department in Lima, Peru.
AB  - BACKGROUND: Overcrowded emergency departments (EDs) are used by undiagnosed
      tuberculosis (TB) patients. TB infection control measures are seldom prioritized,
      making EDs potential foci of unrecognised nosocomial transmission. OBJECTIVE: To
      quantify TB infection risk among health care workers in an ED in a high TB-burden
      setting, Lima, Peru, and to evaluate TB infection control measures. METHODS:
      Consenting ED staff were tested for TB infection at baseline and after 1 year
      using the QuantiFERON-TB Gold In-Tube (QFT-G). In parallel, sputum for TB culture
      was requested from patients spending >2 h in the ED, irrespective of presenting
      complaint. Infection control measures were documented and room ventilation
      measured. RESULTS: Over 1 year, there were 2246 TB patient-hours of exposure in
      the ED from 153 different patients. At baseline, 56% of the 70 staff recruited
      were QFT-G-positive; 27 of 31 baseline-negatives consented to follow-up after 1
      year, and eight (30%, all clinical staff) tested positive. Annual incidence of
      infection was 1730 per 100,000 population. TB infection control measures were sub
      optimal, with no patient screening, no isolation rooms, inadequate ventilation
      and sporadic respirator use. CONCLUSIONS: ED staff were exposed to an
      unexpectedly large TB burden in the workplace, resulting in a high rate of TB
      infection. TB infection control should be prioritized in EDs, especially in high
      prevalence settings.

PMID- 20819257
TI  - Application of modern microbiological diagnostic methods for tuberculosis in
      Macha, Zambia.
AB  - SETTING: Macha, Zambia. OBJECTIVE: To assess the benefits of auramine-O staining
      fluorescence microscopy and Mycobacterial Growth Indicator Tube (MGIT) liquid
      culture with molecular identification in tuberculosis (TB) diagnostics. DESIGN:
      One hundred patients suspected of TB were subjected to three sputum sample
      examinations applying Ziehl-Neelsen (ZN) and auramine-O staining and MGIT
      culture. Positive cultures were identified using the GenoType CM assay; cultures
      identified as Mycobacterium tuberculosis complex were the gold standard for a
      diagnosis of TB. RESULTS: The 100 patients produced 271 sputum samples; of these,
      30 patients had positive cultures. M. tuberculosis complex bacilli were isolated
      in 17 (56.7%) patients, non-tuberculous mycobacteria (NTM) in 11 (36.7%) and
      other acid-fast bacilli in two. Forty-eight samples (17.7%) were contaminated.
      Auramine-O detected 16 (57.1%) patients culture-positive for mycobacteria and 12
      patients with culture-proven TB, vs. respectively 8 (28.6%, P = 0.008) and 7
      (41.2%, P = 0.044) for ZN. Three of eight auramine-positive/ZN-negative patients
      were culture-positive for NTM only. CONCLUSION: The auramine-O method
      significantly increases sensitivity, although the higher NTM detection rate
      implies that this does not in itself lead to a more accurate diagnosis of TB.
      MGIT culture is highly sensitive, although contamination rates were a drawback;
      the high frequency of NTM isolation warrants a robust identification method.

PMID- 20819258
TI  - Why do tuberculosis patients default in Tashkent City, Uzbekistan? A qualitative
      study.
AB  - BACKGROUND: Tuberculosis (TB) control in Tashkent City, Uzbekistan, is organised
      in accordance with the DOTS strategy. Intensive phase treatment is provided in
      hospital, while the continuation phase is given on an ambulatory basis. In 2005,
      the defaulter rate was 21%. An earlier quantitative study explored when patients
      default and identified some of the risk factors associated with default, but did
      not answer the question: 'Why do patients default?' OBJECTIVE: To investigate
      reasons for defaulting and to identify possible solutions. METHODS: We conducted
      a qualitative follow-up study consisting of 32 in-depth interviews with
      defaulters, patients who had completed treatment and health care providers.
      RESULTS: Communication between patients and health care staff is poor. Patients
      lack proper information on TB and its treatment. There is a widespread belief
      that TB is not curable. Hospitalisation is problematic due to poor general
      conditions in TB hospitals, costs incurred by patients during hospitalisation and
      because TB patients need to earn a living or take care of their families.
      CONCLUSION: Poor communication between health care staff and TB patients is a key
      issue underlying several of the causes of default identified, and needs to be
      addressed. Reducing the period of hospitalisation may also improve adherence to
      TB treatment.

PMID- 20819259
TI  - Piloting the use of personal digital assistants for tuberculosis and human
      immunodeficiency virus surveillance, Kenya, 2007.
AB  - SETTING: Improved documentation of human immunodeficiency virus (HIV) testing and
      care among tuberculosis (TB) patients is needed to strengthen TB-HIV programs. In
      2007, Kenya piloted the use of personal digital assistants (PDAs) instead of
      paper registers to collect TB-HIV surveillance data from TB clinics. OBJECTIVE:
      To evaluate the acceptability, data quality and usefulness of PDAs. DESIGN: We
      interviewed four of 31 district coordinators who collected data in PDAs for
      patients initiating TB treatment from April to June 2007. In 10 of 93 clinics, we
      randomly selected patient records for comparison with corresponding records in
      paper registers or PDAs. Using Cochran-Mantel-Haenszel tests, we compared missing
      data proportions in paper registers with PDAs. We evaluated PDA usefulness by
      analyzing PDA data from all 93 clinics. RESULTS: PDAs were well accepted. Patient
      records were more frequently missing (28/97 vs. 1/112, P < 0.001) and data fields
      more frequently incomplete (148/1449 vs. 167/2331, P = 0.03) in PDAs compared
      with paper registers. PDAs, however, facilitated clinic-level analyses: 48/93
      (52%) clinics were not reaching the targets of testing >or=80% of TB patients for
      HIV, and 8 (9%) clinics were providing <80% of TB-HIV co-infected patients with
      cotrimoxazole (CTX). CONCLUSION: PDAs had high rates of missing data but helped
      identify clinics that were undertesting for HIV or underprescribing CTX.

PMID- 20819260
TI  - Serum 25-hydroxy-vitamin D3 concentrations increase during tuberculosis treatment
      in Tanzania.
AB  - SETTING: Vitamin D deficiency is associated with susceptibility to active
      tuberculosis (TB) in many settings. In vitro studies and studies on human
      volunteers showed that two of the first-line anti-tuberculosis drugs, isoniazid
      and rifampicin, reduce 25-hydroxy vitamin D (25[OH]D) concentrations. OBJECTIVE:
      To study changes in vitamin D status during treatment of Tanzanian hospitalised
      patients with pulmonary TB (PTB). DESIGN: We compared serum 25[OH]D
      concentrations in 81 Tanzanian PTB patients before and after 2 months of
      treatment. RESULTS: Median serum 25[OH]D concentrations increased from 91 nmol/l
      at baseline to 101 nmol/l after 2 months of TB treatment (median increase 6.0
      nmol/l, IQR -0.7-25.0, P = 0.001). Median serum parathyroid hormone
      concentrations increased from 1.6 to 2.0 pmol/l (median increase 0.46, IQR -0.2
      1.1, P < 0.001). CONCLUSION: 25[OH]D serum concentrations increased during the
      first 2 months of TB treatment in 81 PTB patients in northern Tanzania. Improved
      dietary intake and increased sunlight exposure may have contributed to the
      increased 25[OH]D concentrations.

PMID- 20819261
TI  - Pleural fluid cytokines correlate with tissue inflammatory expression in
      tuberculosis.
AB  - SETTING: A tertiary care research centre in Sao Paolo, Brazil. OBJECTIVE: To
      quantify interleukin (IL) 8, tumour necrosis factor alpha (TNF-alpha), vascular
      endothelial growth factor (VEGF) and transforming growth factor beta(1) (TGF
      beta(1)) in pleural fluid from tuberculous patients, correlating its values with
      the histopathological patterns in pleural biopsies. DESIGN: Cytokines were
      quantified in patients with transudates secondary to congestive heart failure (n
      = 8) and exudates secondary to tuberculosis (TB; n = 39). In parietal pleural
      biopsies from TB patients, the histological patterns of the inflammatory response
      were quantified by morphometric analysis (stereological point-counting method).
      RESULTS: IL-8, TNF-alpha, VEGF and TGF-beta(1) levels were higher in TB than in
      transudates. A positive correlation existed between components of the fibrinoid
      exudative phase with pleural fluid IL-8 (R = 0.52, P = 0.004) and VEGF (R = 0.42,
      P = 0.0021) levels. A negative correlation existed between pleural fluid IL-8 (R
      = -0.37, P = 0.048) and VEGF (R = -0.44, P = 0.0015) levels with tissue
      components of fibroproliferation. CONCLUSION: The high pleural levels of TNF
      alpha, IL-8, VEGF and TGF-beta(1) suggest the involvement of these cytokines in
      the TB immunological response. The positive correlation between pleural fluid IL
      8 and VEGF with the components of the acute exudative phase and the negative
      correlation between these cytokines with the fibroproliferative components
      suggest a temporary inflammatory response in the pleural space.

PMID- 20819262
TI  - Association of P2X7 receptor +1513 (A-->C) polymorphism with tuberculosis in a
      Punjabi population.
AB  - BACKGROUND: Development of tuberculosis (TB) disease is an outcome of complex
      host-pathogen interactions. The purinergic P2X(7) receptors are adenosine
      triphosphate gated molecules shown to induce killing of intracellular
      Mycobacterium tuberculosis, followed by apoptosis of the infected macrophage. A
      single nucleotide polymorphism in exon 13 of the P2X(7) receptors gene at +1513
      position has been shown to abolish the function of this receptor and to be
      associated with increased susceptibility to TB in some ethnic groups. OBJECTIVE:
      To explore the association of +1513 (A-->C) polymorphism in TB patients in
      Punjab, North India. DESIGN: A case-control study was conducted by studying
      peripheral blood samples from 204 TB patients (181 pulmonary, 23 extra-pulmonary)
      and 177 controls with no history of TB. P2X(7) +1513 (A-->C) polymorphism was
      studied using amplification refractory mutation system analysis. RESULT: The
      distribution of +1513 A/C genotypes in the TB patient and the control groups
      revealed a statistically significant association with TB (P = 0.002). CONCLUSION:
      The +1513C allele is a risk factor for the development of TB in the North Indian
      Punjabi population.

PMID- 20819263
TI  - Concentration of Mycobacterium tuberculosis from sputum using ligand-coated
      magnetic beads.
AB  - SETTING: Direct sputum smear microscopy is usually less sensitive than the
      indirect approach using concentration by centrifugation, but laboratories often
      do not have access to appropriate equipment. An alternative method of sample
      concentration has been developed based on magnetic beads coated with a polymeric
      ligand that binds mycobacteria species. The 'TB-Beads' technology allows manual
      sample preparation using simple magnetic separation equipment prior to
      microscopy. OBJECTIVE: 1) To evaluate TB-Beads, in combination with fluorescent
      auramine staining, on a blind panel of 129 frozen samples from the Special
      Programme for Research & Training in Tropical Diseases (TDR), the World Health
      Organization sputum bank; and 2) to compare the microscopy results to indirect
      microscopy, culture and the clinical data already available on these samples.
      RESULTS: The correlation between the TB-Beads protocol and indirect microscopy
      was 96.1% (124/129). The TB-Beads protocol was 89.4% (76/85) sensitive compared
      to culture and 77.8% (77/99) sensitive compared to clinical diagnosis.
      CONCLUSION: Capture by magnetic particles yields a concentrated sample that is
      immobilised over a defined area of the slide, thereby aiding microscopic
      analysis. TB-Beads allow laboratories that currently perform comparatively
      insensitive direct microscopy to implement a concentration method that has the
      potential to improve TB detection rates.

PMID- 20819264
TI  - Evaluation of MGIT 960 and the colorimetric-based method for tuberculosis drug
      susceptibility testing.
AB  - SETTING: Dr Cetrangolo Hospital, Buenos Aires Province, Argentina. OBJECTIVE:
      Evaluation of the BACTEC Mycobacteria Growth Indicator Tube (MGIT) 960 system and
      the colorimetric-based method (CMM) for first- and second-line drug
      susceptibility testing (FL-DST, SL-DST) against Mycobacterium tuberculosis.
      DESIGN: FL-DST was studied using SIRE MGIT 960. Minimal inhibitory concentrations
      (MICs) for isoniazid (INH), streptomycin, rifampicin (RMP), ethambutol (EMB) and
      levofloxacin (LVX) were also determined by CMM using 3-(4,5-dimethylthiazolyl-2)
      2,5-diphenyltetrazolium bromide (MTT). MICs for amikacin (AMK), kanamycin (KM),
      capreomycin (CPM), ethionamide (ETH), cycloserine, ofloxacin (OFX), linezolide
      (LZ) and moxifloxacin (MFX) were determined on 94 multidrug-resistant M.
      tuberculosis isolates by MGIT 960 and CMM. Statistical methods were applied to
      define drug-susceptible and drug-resistant isolates on the basis of the
      comparison between results obtained by gold standards. RESULTS: A total of 1626
      clinical isolates were studied. Critical drug concentrations could be defined in
      less than 10 days for both CMM and MGIT 960. CMM was cheaper but more laborious
      than MGIT 960. The highest performances of both methods were achieved for AMK,
      RMP, OFX, LZ and MFX, followed by INH, ETH, KM, CPM and LVX (tested only by CMM).
      CONCLUSIONS: Both methods could be implemented as rapid diagnostic tools to
      detect drug-resistant isolates in clinical practice.

PMID- 20819265
TI  - The changing pattern of clinical Mycobacterium avium isolation in the
      Netherlands.
AB  - SETTING: National Mycobacteria Reference Laboratory, The Netherlands. OBJECTIVE:
      To assess the role of factors other than laboratory improvements in the
      increasing frequency of isolation of non-tuberculous mycobacteria (NTM) in the
      Netherlands; laboratory improvements are often considered key factors in this
      increase. DESIGN: Laboratory database study. All clinically isolated NTM referred
      to the national reference laboratory between January 2000 and January 2007 were
      retrieved from the laboratory database and categorised by species, patient age
      group and sample origin. Data were compared with national demographic data.
      RESULTS: Clinical Mycobacterium avium isolates accounted for most of the increase
      in referred NTM. The number of respiratory M. avium samples in patients aged >40
      years increased over time. This age group increased in size during the study. In
      this age group, the prevalence of chronic obstructive pulmonary disease (COPD)
      increased during the study period. M. avium isolation from lymph nodes in
      children remained stable, whereas extra-pulmonary M. avium isolation in the
      middle age group, including human immunodeficiency virus associated bloodstream
      isolates, decreased. CONCLUSIONS: The increasing NTM notification in the
      Netherlands is unlikely to have been a result of laboratory improvements alone:
      the ageing population with an increasing prevalence of COPD is likely as
      important. Environmental characteristics may specifically favour M.avium.

PMID- 20819266
TI  - The challenge of osteo-articular tuberculosis in the twenty-first century: a 15
      year population-based study.
AB  - SETTING: Serbia, an intermediate tuberculosis (TB) incidence country in socio
      economic transition. OBJECTIVE: To examine the epidemiological and clinical
      pattern of osteo-articular TB (OATB) in Serbia over 15 years. DESIGN: This
      retrospective observational study included OATB cases diagnosed between 1 January
      1993 and 31 December 2007, according to the National Referral Institute of Lung
      Diseases and TB in Belgrade and the Central TB Register. Population estimates
      with extrapolations were based on 1991 and 2002 census data. RESULTS: The 295
      OATB cases represented 10.9% (range 5.3-20.2) of all extra-pulmonary TB cases
      notified in Serbia over the period. One tenth of these were relapses. The
      incidence rate showed a significant increasing trend (y = 0.1167 + 0.0175x, R(2)
      = 0.3196), with an average age-specific incidence rate of 0.26 per 100 000
      population. The peak number of cases was in the 45-64 year age group for both men
      and women. The average male:female ratio was 0.85. The outcome was favourable for
      279 of the 295 patients (94.6%). In addition to a standardised chemotherapy
      regimen, 25.4% patients underwent surgery. CONCLUSION: The increasing time trend
      of OATB is caused by increased morbidity, a higher TB detection rate and better
      notification. Although rare in children, OATB remains a challenge in clinical
      practice.

PMID- 20819267
TI  - Frequency of adverse events and mortality in patients with pleural empyema in a
      public referral hospital in Mexico City.
AB  - SETTING: Adverse events (AEs) that occur during medical treatment are a public
      health problem. OBJECTIVE: 1) To measure the prevalence of AEs, 2) to
      characterize those that occur in patients diagnosed with empyema and 3) to
      analyze the mortality rate associated with the presence of empyema. DESIGN:
      Retrospective case series based on a review of files of patient diagnosed with
      empyema. RESULTS: A total of 347 files were assessed, reporting 96.6% of the
      total number of patients diagnosed with empyema in that period. There were 176
      AEs reported for 150 of the patients. The frequency of at least one AE was 43%,
      with prolonged hospitalization being the most frequent condition. In these cases,
      97% of the AEs were considered preventable. Intrahospital mortality was 4.8%,
      with age (HR for every 5 years 1.21, 95%CI 1.08-1.35, P < 0.001) and the presence
      of diabetes mellitus (HR 2.26, 95%CI 1.0-5.0, P = 0.04) being significant
      associated factors. CONCLUSION: There was a high frequency of AEs in patients
      with empyema, but most were considered preventable, especially the length of
      hospitalization, which could be reduced through timely surgery.

PMID- 20819269
TI  - Beijing family Mycobacterium tuberculosis isolated from throughout Japan:
      phylogeny and genetic features.
AB  - To estimate the current population genetic structure of Mycobacterium
      tuberculosis in Japan, phylogenetic traits were analysed for 237 Beijing family
      strains isolated from tuberculosis patients throughout the country. Unlike
      previous reports from other countries, the ancient Beijing sublineage was
      predominant throughout Japan. Clustering analysis based on JATA-VNTR (Japan Anti
      Tuberculosis Association variable numbers of tandem repeats), a specialised set
      of VNTR for the discrimination of Japanese M. tuberculosis strains, revealed high
      similarity of the modern Beijing sublineage strains, irrespective of their
      geographic origin. JATA-VNTR might be useful for the phylogenetic classification
      in populations where ancient Beijing strains are frequently isolated.

PMID- 20819268
TI  - Elevated plasma adiponectin levels in patients with chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Adiponectin is an anti-inflammatory adipokine that may play a role in
      chronic obstructive pulmonary disease (COPD) pathogenesis. OBJECTIVE: To
      investigate the relationship between adiponectin, interleukin (IL) 6, IL-8 and C
      reactive protein (CRP) and COPD by evaluating these biomarkers in ever-smokers
      with or without the disease. METHOD: Plasma levels of adiponectin, IL-6, IL-8 and
      CRP were measured using commercially available kits in COPD patients (n = 71),
      healthy ever-smokers (n = 62) and non-smokers (n = 51). RESULTS: There were
      significant increases in plasma adiponectin, IL-6 and CRP in COPD patients
      (median [IQR] 4.39 microg/ml [2.68-6.98], 4.19 pg/ml [<2.40-6.40], 8.75 mg/l
      [4.26-40.63], respectively) compared to healthy ever-smokers (1.90 microg/ml
      [0.86-2.86], <2.40 pg/ml [<2.40-2.77], 3.71 mg/l [1.97-10.37 mg/l], respectively,
      P < 0.001) and non-smokers (1.76 microg/ml [1.34-2.52], <2.40 pg/ml [<2.40-2.78],
      3.12 mg/l [2.11-5.71], respectively, P < 0.001). COPD patients had lower plasma
      IL-8 levels than healthy ever-smokers. Among ever-smokers with or without COPD,
      plasma adiponectin, IL-6 and CRP levels were inversely correlated with forced
      expiratory volume in 1 second (% predicted) after adjustment for age, body mass
      index, smoking status and pack-years. CONCLUSION: Our findings suggest that in
      COPD patients, adiponectin might be associated with COPD pathogenesis.

PMID- 20819270
TI  - Feasibility of the T-SPOT.TB assay for the immunodiagnosis of smear-positive
      pulmonary tuberculosis using induced sputum.
AB  - Diagnosis of active tuberculosis (TB) remains a challenge. In this a preliminary
      proof-of-concept study seeking to determine the feasibility of using cells from
      induced sputum for the immunodiagnosis of pulmonary TB (PTB) in smear-positive
      cases, a total of 75 subjects with PTB (n = 31) and healthy controls (n = 44)
      underwent the blood T-SPOT(R).TB test. T-SPOT.TB in induced sputum samples was
      performed in 29 of 31 TB and 14/44 healthy subjects. Induced sputum T-SPOT.TB
      results were indeterminate in 72.6% of TB and 100% of healthy subjects. The T
      SPOT.TB test in induced sputum samples does not seem a feasible method for
      diagnosing PTB and needs improvement.

PMID- 20819271
TI  - Predictive values of QuantiFERON-TB Gold testing in screening for tuberculosis
      disease in asylum seekers.
AB  - Screening with chest X-ray and the Mantoux test (the tuberculin skin test [TST])
      is compulsory for adult asylum seekers who arrive in Norway. In 2005-2006, we
      included 823 asylum seekers in a study of the QuantiFERON-TB Gold test (QFT-G),
      and followed them for 23-32 months. Eight subjects with a positive and one with a
      negative QFT-G test were diagnosed with tuberculosis (TB). The positive (PPV) and
      negative predictive values (NPV) for TB were respectively 3.3% and 99.8%. The PPV
      was 2.3% and the NPV 99.1% for TST >or= 15 mm, and the NPV was 99.5% for TST >or=
      6 mm in combination with a negative QFT-G.

PMID- 20819272
TI  - Can the drug-driven dependency and deprivation effect be used as a therapeutic
      tool in tuberculous patients?

PMID- 20819274
TI  - Anti-tuberculosis drug resistance in Dohuk, Iraq.

PMID- 20819275
TI  - Discovery and early development of non-suppressed ion chromatography.
AB  - This year marks the 30th anniversary of the publication of Non-Suppressed Ion
      Chromatography, which is a method for the rapid separation of anions with on-line
      conductimetric detection. In this method, the separation column is connected
      directly to the conductimetric detector. This single-column method is a simpler
      technique than the original suppressed ion chromatography method, which requires
      a large suppressor column to reduce the background conductance. In the new
      method, the background signal is reduced to a manageable level simply by using an
      ion-exchange separation column of low exchange capacity that lowers the eluent
      concentration needed for separation. The eluent ion used for separation is chosen
      based on having large, bulky structure, which lowers the equivalent conductance
      and facilitates detection of the sample anions. This is a personal account of the
      initial discovery and early development of non-suppressed ion chromatography. The
      circumstances for the discovery are recounted by the two authors. Methods are
      described for determination of anions, cations with indirect detection, and
      techniques for increasing detection sensitivity. A fundamental equation for the
      prediction of ion chromatography detector response is given, and the development
      of several types of detection schemes for ion chromatography is discussed.
      Finally, the impact of non-suppressed ion chromatography is discussed together
      with comments on the discovery process.

PMID- 20819276
TI  - Determination of low-ppt levels of acetate, propionate, and formate in
      semiconductor-grade deionized water via ion chromatography.
AB  - The goals of this research were the development of a method to determine acetate,
      propionate, and formate at low part-per-trillion (ppt; w/w) levels in deionized
      water, and the assessment of sources of variability and contamination associated
      with the method; both objectives were met. A calibration study involving six
      replicates of each of four standards (blank, 20, 50, and 80 ppt) resulted in
      straight-line (with ordinary-least-squares fitting) curves for all analytes. At
      95% confidence, the half-widths of the prediction intervals were +/- 30, 14, and
      14 ppt for the three analytes, respectively. Much of the acetate and formate seen
      in blanks was found to originate in the deionized water system itself. For
      formate, peak heights increased with water temperature.

PMID- 20819277
TI  - Direct injection, simple and robust analysis of trace-level bromate and bromide
      in drinking water by IC with suppressed conductivity detection.
AB  - Bromide is ubiquitously found in drinking water. It is introduced into source
      water primarily by contact with bromide-containing soils or seawater having high
      bromide content. Bromide is converted into carcinogenic bromate during ozonation
      processes employed in some drinking water and wastewater treatment plants.
      Therefore, monitoring of bromate in drinking water and its precursor bromide in
      source water is required. The purpose of this study was to survey bromide and
      bromate concentrations in randomly selected bottle waters of various brands and
      several tap water samples in the coastal Houston area using a direct-injection
      ion chromatography (IC) and a suppressed conductivity system. The method employs
      a simple isocratic IC with loop injection with calculated detection limit of
      0.009 microg/L for bromate and 0.028 microg/L for bromide (250-microL sample
      volume). Allowing the detection of both species at the microg/L level in drinking
      water, this method does not require specialized instrumentation such as two
      dimensional IC, expensive sample preparation, or post-column reactions. The
      results show that, whereas bromate remains undetected in all five tap water
      samples, there are significant high concentrations of bromide in the coastal
      Houston area (294.79 +/- 56.97 microg/L). Its link to potential seawater
      intrusion need to be further investigated. For bottle water samples randomly
      collected, 18.2% (2 out of 11) showed detectable amount of both bromide and
      bromate. The detection of bromate coincides with those bottle water samples that
      underwent ozonation treatment. Further sample campaign with exclusively ozonated
      bottle water samples (n = 19) showed 100% detection rate for both bromide and
      bromate. The 99% confidence intervals were 14.45-37.97 microg/L and 0.32-2.58
      microg/L for bromide and bromate, respectively. The highest level of bromate
      among all ozonated bottle water samples was 7.57 microg/L, a concentration close
      to the U.S. EPA prescribed limit for drinking water standard. Regression analysis
      indicated that although a positive correlation exists between bromide and bromate
      concentrations, such a correlation is not statistically significant. This finding
      is not unexpected since a variety of other parameters in the ozonation process
      (such as water quality, ozone dose, and time in addition to bromide
      concentration) affect the formation of bromate. Our results strongly suggest that
      cautions should be exercised to examine the potential formation of bromate when
      source water from coastal zone undergoes ozonation treatment. Another strong
      proof of our findings is that all the tap waters collected were treated in
      jurisdictions that do not use ozonation for disinfection. The fact that none of
      these tap water samples contained bromate (despite an abundance in bromide)
      proves our hypothesis even further.

PMID- 20819278
TI  - Determination of amines in the presence of excess ammonia by ion chromatography
      mass spectrometry.
AB  - A new method for the simultaneous determination of several amines in the presence
      of an excess of ammonia by ion chromatography-mass spectrometry detection was
      developed. Current methods using ion chromatography with suppressed conductivity
      detection are not selective enough to determine small amines at the required
      level of 10 microg/L or preferably lower in the presence of a large excess of
      ammonia (approximately 1 mg/L) without resorting to time-consuming sample pre
      treatment techniques. By using mass spectrometric detection, which is capable of
      resolving eluting compounds on their m/z values, an additional dimension of
      confirmation is added to the analysis. Detection based on the analytes m/z value
      overcomes problems such as co-elution or background interferences that complicate
      the quantification when using conductivity detection. The optimal conditions for
      mass spectrometry detection of amines in the presence of an excess of ammonia
      were investigated by a four-factor central composite design. The four factors
      investigated were scan time, cone voltage, probe temperature, and needle voltage.
      Evaluation of the obtained experimental data showed that detection limits were up
      to a factor of 100 lower when using mass spectrometry as the detection technique
      instead of the conventional suppressed conductivity detection. Detection limits
      of 1 microg/L and lower can be achieved for the six amines investigated in the
      presence of a large excess of ammonia (approximately 1 mg/L).

PMID- 20819279
TI  - Time-resolved measurement of the ionic fraction of atmospheric fine particulate
      matter.
AB  - From the health stand-point, atmospheric particulate matter (PM) is regulated
      through PM(10) and PM(2.5) conventions by the Directive 2008/50/EC. The Directive
      points out the negative impact on human health due to PM(2.5) and recognizes that
      no threshold has been identified for such pollutant at which no risk is foreseen
      for the population. Then, the goal is to pursue a general reduction of PM(2.5).
      Traditionally, the analytical techniques used to monitor the PM water-soluble
      inorganic ionic fraction involve filter-based procedures to collect, process, and
      analyze samples. Data obtained, while accurate, lack temporal resolution. Time
      resolution is required on the time-scale of the evolution of the planetary
      boundary layer to understand the processes that govern transport and
      transformation of atmospheric aerosol. In this paper, we investigated PM(2.5)
      nitrite, nitrate, sulfate, chloride, sodium, ammonium, calcium, and magnesium
      ions using a URG 9000-D aerosol ion monitor with 1-h time-resolution and
      detection limit of 0.1 microg/m(3). The gas phase is separated from the aerosol
      phase with a liquid diffusion parallel-plate denuder. Daily trends of the
      pollutants measured in downtown Rome are discussed and interpreted with reference
      to atmospheric conditions.

PMID- 20819280
TI  - Determination of trace inorganic anions in weak acids by single-pump column
      switching ion chromatography.
AB  - Ion chromatography has been proposed for the determination of three common
      inorganic anions (chloride, nitrate, and sulfate) in nine weak acids (tartaric
      acid, citric acid, formic acid, acetic acid, metacetonic acid, butyric acid,
      butanedioic acid, hexafluorophosphoric acid, and salicylic acid) using a single
      pump, two valves, a single eluent, and a single conductivity detector. The
      present system uses ion exclusion, concentrator, and anion-exchange columns
      connected in series via 6-port and 10-port valves in a Dionex ICS-2100 ion
      chromatograph. The valves were switched for the determination of three inorganic
      anions from weak acids in a single chromatographic run. Sample matrices of weak
      acids with a series of concentrations can be investigated. Complete separations
      of the previously mentioned anions are demonstrated within 40 min. Under the
      optimum conditions, the relative standard deviation values ranged from 1.3 to
      3.8%. The detection limits of the three inorganic anions (S/N = 3) were in the
      range of 0.3-1.7 microg/L. The recoveries were in the range of 75.2-117.6%. With
      this system, automation for routine analysis, short analysis time, and low cost
      can be achieved.

PMID- 20819281
TI  - Environmental applications of ion chromatography in Eastern and Central Europe.
AB  - Environmental analytics is one of the most important applications of ion
      chromatography. It includes determination of ions in water and wastewater as well
      as in gaseous and solid ones. Nowadays, ion chromatography has almost completely
      displaced the classical methods of ion determination in these areas. In spite of
      the fact that the ion chromatography has been officially present in the
      scientific world for 36 years, its role and popularity is highly diversified in
      various countries and regions of the world. In highly industrialized countries,
      it has been a reference method of water and wastewater analysis for years. In
      other parts of the world, it is not used and appreciated sufficiently despite its
      undeniable advantages. The following paper is a short overview of the most highly
      cited scientific and research institutions that conduct research in terms of
      environmental applications of ion chromatography in Eastern and Central Europe.
      Furthermore, the paper presents a list of a number of scientific papers referring
      to the discussed area, published in the years 1996-2009 in some of the most
      highly cited international scientific journals, and concerning publications of
      scientists from Eastern and Central Europe seen against the background of Europe
      and the world.

PMID- 20819282
TI  - Wider pore superficially porous particles for peptide separations by HPLC.
AB  - Fused-core superficially porous particles have recently created considerable
      interest for high-performance liquid chromatography separations because of their
      unusual high column efficiency and much lower back pressure when compared to sub
      2-microm particles. With superficially porous particles, larger solutes can move
      rapidly in and out of a thin porous shell, resulting in reduced band broadening
      at higher mobile phase velocities for greater separation speeds. The original
      silica fused-core particles were 2.7 microm in diameter with a 0.5-microm thick
      shell of 90 A pores designed for the fast separation of small molecules with
      molecular weights of less than approximately 5000. This manuscript describes new
      fused-core particles with similar physical characteristics except with a porous
      shell of 160 A pores designed specifically for rapidly separating peptides (and
      some small proteins) with molecular weights up to approximately 15,000 Daltons.
      Because of the larger pore size, restricted diffusion of these larger molecules
      is not seen since ready access to the entire porous shell is featured. Data are
      given to define sample loading qualities for columns of these new particles.
      Column stability studies indicate that these particles bonded with a sterically
      protected C(18) stationary phase can be used at low pH and higher temperatures
      with excellent results. The wider-pore particles of this study are shown to be
      particularly useful with a mass spectrometer detector for the rapid gradient
      separation of peptides using both volatile trifluoroacetic acid and formic acid
      containing mobile phases. Examples are provided for the separation of complex
      peptide mixtures to illustrate the capabilities for columns of these new wider
      pore, fused-core particles.

PMID- 20819283
TI  - A high-throughput multivariate optimization for the simultaneous
      enantioseparation and detection of barbiturates in micellar electrokinetic
      chromatography-mass spectrometry.
AB  - The R- and S-configurations of barbiturates display differences in potency and
      biological activity. In this study, multivariate micellar electrokinetic
      chromatography-mass spectrometry (MEKC-MS) approach for the simultaneous analysis
      of three chiral barbiturates (mephobarbital, pentobarbital, and secobarbital) is
      developed using a polymeric chiral surfactant. After screening 11 amino acid
      polymeric surfactants, polysodium N-undecenoxycarbonyl-L-isoleucinate (poly-L
      SUCIL) was found to be the best chiral selector. The multivariate central
      composite design (CCD) is used to optimize the chiral resolution, decrease the
      total analysis time, and improve the ESI-MS signal-to-noise (S/N) ratio. In the
      preliminary set of experiments, the ranges of the factors investigated in the
      multivariate approaches are determined. Next, the CCD design is conducted to
      determine the best overall chiral resolution with shortest possible run times.
      This optimization resulted in simultaneous enantioseparation in less than 32 min
      of all three barbiturates with 3-5 fold higher sensitivity by MS compared to UV
      detection. The adequacy of the multivariate model is validated by three replicate
      experimental runs at the predicted optimum conditions. The predicted results of
      MEKC-MS are found to be in good agreement with the experimental data for
      migration times, resolution, and S/N ratio. The optimized method provided good
      results in terms of linearity and recovery values of chiral barbiturates spiked
      in human serum after solid-phase extraction procedure.

PMID- 20819284
TI  - Determination of phenolic disinfectants in consumer products by capillary
      electrophoresis with amperometric detection.
AB  - Numerous disinfection products are widely used in daily life to kill pathogenic
      microorganisms. However, most disinfectants are organic compounds that might be
      hazardous to the environment and humans when used excessively. Phenolic
      disinfectants in disinfection products are investigated using a high-performance
      capillary electrophoresis-amperometric detection method. Under the optimum
      conditions, five commonly used disinfectants can be well-separated within 19 min
      at the separation voltage of 18 kV in a 80 mmol/L borax running buffer (pH 9.2),
      and adequate extraction was obtained with ethanol for the determination of the
      five compounds. Satisfactory recovery (93.5-106.0%), intra-day repeatability of
      the peak current (< 2.9%), and detection limits (1.6 x 10(-7) - 3.8 x 10(-8)
      g/mL) for the method are achieved. This proposed procedure is successfully used
      to analyze different samples of disinfection products.

PMID- 20819285
TI  - Simultaneous determination of piracetam and its four impurities by RP-HPLC with
      UV detection.
AB  - A simple and rapid high-performance liquid chromatographic method for the
      separation and determination of piracetam and its four impurities, 2
      oxopyrrolidin-1-yl)acetic acid, pyrrolidin-2-one, methyl (2-oxopyrrolidin-1
      yl)acetate, and ethyl (2-oxopyrrolidin-1-yl)acetate, was developed. The
      separation was achieved on a reversed-phase C(18) Nucleosil column (25 cm x 0.46
      cm, 10 microm). The mobile phase is composed of an aqueous solution containing
      0.2 g/L of triethyl amine-acetonitrile (85:15, v/v). The pH of the mobile phase
      was adjusted to 6.5 with phosphoric acid at a flow rate of 1 mL/min at ambient
      temperature and UV detection at 205 nm. The developed method was found to give
      good separation between the pure drug and its four related substance. The
      polynomial regression data for the calibration plots showed good linear
      relationship in the concentration range of 50-10,000 ng/mL, 25-10,000 ng/mL, 45
      10,000 ng/mL, 34-10,000 ng/mL, and 55-10,000 ng/mL, respectively, with r(2) =
      0.9999. The method was validated for precision, accuracy, ruggedness, and
      recovery. The minimum quantifiable amounts were found to be 50 ng/mL of
      piracetam, 25 ng/mL of 2-oxopyrrolidin-1-yl)acetic acid, 45 ng/mL of pyrrolidin-2
      one, 34 ng/mL of methyl (2-oxopyrrolidin-1-yl)acetate, and 55 ng/mL of ethyl (2
      oxopyrrolidin-1-yl)acetate. Statistical analysis proves that the method is
      reproducible and selective for the estimation of piracetam as well as its related
      substance. As the method could effectively separate the drug from the related
      substances, it can be employed as a stability-indicating one. The proposed method
      shows high efficiency, allowing the separation of the main component piracetam
      from other impurities.

PMID- 20819286
TI  - Stability indicating LC method for simultaneous determination of irbesartan and
      hydrochlorothiazide in pharmaceutical preparations.
AB  - A simple and precise stability-indicating liquid chromatography method is
      developed and validated for the quantitative simultaneous estimation of
      irbesartan (IRB) and hydrochlorothiazide (HCTZ) in combined pharmaceutical dosage
      form. A chromatographic separation of the two drugs was achieved with an Ace5
      C(18) 25-cm analytical column using buffer-acetonitrile (70:30 v/v). The buffer
      used in mobile phase contains 50 mM ammonium acetate pH adjusted 5.5 with acetic
      acid. The instrumental settings are flow rate of 1.5 mL/min, column temperature
      at 30 degrees C, and detector wavelength of 235 nm using a photodiode array
      detector. IRB, HCTZ, and their combination drug products were exposed to thermal,
      photolytic, hydrolytic, and oxidative stress conditions, and the stressed samples
      were analyzed by the proposed method. Peak homogeneity data of IRB and HCTZ is
      obtained using photodiode array detector. In the stressed sample chromatograms,
      it demonstrated the specificity of the assay method for their estimation in
      presence of degradation products. The described method shows excellent linearity
      over a range of 10-200 microg/mL for IRB and 5-100 microg/mL for HCTZ.
      Methylparaben was used as internal standard. The correlation coefficient for IRB
      and HCTZ are 0.998 and 0.999. The mean recovery values for IRB and HCTZ ranged
      from 100.45% to 101.25%. The limit of detection for IRB and HCTZ were 0.019 and
      0.023 microg/mL, respectively, and the limit of quantification were 0.053 and
      0.070 microg/mL, respectively. The proposed method was suitable for quantitative
      determination and stability study of IRB and HCTZ in pharmaceutical preparations
      and also can be used in the quality control of bulk manufacturing and
      pharmaceutical dosage forms.

PMID- 20819287
TI  - Stability indicating LC method for the simultaneous determination of amlodipine
      and olmesartan in dosage form.
AB  - A simple, rapid, and precise method is developed for the quantitative
      simultaneous estimation of amlodipine (AM) and olmesartan (OL) in combined
      pharmaceutical dosage form. A chromatographic separation of the two drugs was
      achieved with an ACE 5 C(18) 25-cm analytical column using buffer-acetonitrile
      (60:40, v/v). The resolution between OL and AM was found to be more than 12.
      Theoretical plates for OL and AM were 6970 and 11,841, respectively. Tailing
      factor for OL and AM was 0.90 and 0.98, respectively. OL, AM, and combination
      drug product were exposed to thermal, photolytic, hydrolytic, and oxidative
      stress conditions, and the stressed samples were analyzed by the proposed method.
      Peak homogeneity data of OL and AM is obtained by photodiode array detector in
      the stressed sample chromatograms, demonstrating the specificity of the method
      for their estimation in presence of degradation product. The described method
      shows excellent linearity over a range of 20-400 microg/mL for OL and 5-100
      microg/mL for AM. The correlation coefficient for OL and AM are 0.9995 and
      0.9998, respectively. The relative standard deviation for six measurements in two
      sets of each drug in tablets is always less than 2%. The proposed method was
      found to be suitable and accurate for quantitative determination and stability
      study of OL and AM in pharmaceutical preparations.

PMID- 20819288
TI  - Development and validation of a RP-HPLC method for the estimation of netilmicin
      sulfate and its related substances using charged aerosol detection.
AB  - Netilmicin is a semi-synthetic aminoglycoside antibiotic used against a broad
      spectrum of Gram-negative bacteria. A reversed-phase high-performance liquid
      chromatographic method has been developed to determine the composition of
      netilmicin sulfate and to estimate its related substances without pre- or post
      column derivatization. A UV detector cannot be used to detect low levels of known
      and unknown related substances of netilmicin, as it has only a weak UV
      chromophore. A charged aerosol detector was used instead to obtain the high
      sensitivity that was necessary for the intended purpose of the method. This
      method can separate all related substances of netilmicin. A (10 cm x 4.6 mm)
      pentafluorophenyl high-performance liquid chromatographic column from Restek was
      used with a mobile phase consisting of (A) pentafluoropropionic acid-water
      acetonitrile (0.1:96:4, v/v/v) and (B) trifluoroacetic acid-water-acetonitrile
      (1:96:4, v/v/v).

PMID- 20819289
TI  - Separation, purification, and characterization of analogues components of a
      commercial sample of new Fuchsin.
AB  - New Fuchsin (NF), also known as Magenta III, has potential applications in
      photodynamic therapy. The commercial product labeled NF contains two other dye
      components in different proportions, Magenta II and Magenta I (Rosaniline). The
      proportions of NF, Magenta II, and Magenta I determined by reversed-phase high
      performance liquid chromatography (RP-HPLC) in the commercial sample used were
      71.6 +/- 0.4%, 25.2 +/- 0.2%, and 2.8 +/- 0.1% (n = 7), respectively. The
      isolation, purification, and characterization of commercial NF dye components
      were carried out applying different techniques, such as preparative column liquid
      chromatography (PCLC), thin layer chromatography (TLC), RP-HPLC, absorption
      spectrophotometry, nuclear magnetic resonance spectroscopy (NMR), electrospray
      ionization mass spectrometry (ESI-MS), and tandem electrospray ionization mass
      spectrometry (ESI-MS-MS). After separation and isolation, the degree of purity
      obtained for NF compound was higher than 95% and 92% for Magenta II and Magenta I
      compounds, respectively. Therefore, it is essential to ensure a high degree of
      purity of these dyes as raw material to obtain new drugs intended for therapeutic
      treatments.

PMID- 20819290
TI  - Selective determination of ertapenem and imipenem in the presence of their
      degradants.
AB  - Stability-indicative determination of ertapenem (E(RTM)) and imipenem (I(MPM)) in
      the presence of their corresponding open-ring degradation products, the
      metabolites, is investigated. The degradation products have been isolated via
      acid-degradation, characterized, and confirmed. Selective quantification of
      E(RTM) or I(MPM) singly in bulk form, pharmaceutical formulations, and/or in the
      presence of their corresponding degradants is demonstrated. The indication of
      stability has been undertaken under conditions likely to be expected at normal
      storage conditions. Among the chromatographic techniques adopted for
      quantification are coupled thin layer chromatography-densitometry and high
      performance liquid chromatography.

PMID- 20819291
TI  - Conversion investigation for lovastatin and its derivatives by HPLC.
AB  - A high-performance liquid chromatography (HPLC) method was developed for the
      separation of lovastatin (LT) and its derivatives. The conversion of LT and its
      derivatives in alkaline or acidic solution in different storage times was also
      investigated by HPLC. The results showed that LT was present in different forms:
      as a lactone, as lovastatin acid (LA), and as its methyl ester (LM) under acidic
      condition. Well-resolved peaks of three forms compounds of lovastatin were
      separated on a Symmetry C(18) column (4.6 x 250 mm i.d., particle size 5 mum)
      using acetonitrile-water (77:23, v/v) as the mobile phase at pH 3.0. The
      retention time of LA, LT, LM was 6.41 +/- 0.25 min, 8.89 +/- 0.25 min, 9.73 +/-
      0.25 min, respectively. LT only converted to LA when LT was treated with 0.1 M
      NaOH. Under the acidic condition, with the increase of storage time, LT converted
      to LA, following LA would be transformed to LT and LM. Apparently, containing
      high concentrations of methanol in acidic methanol solutions might facilitate the
      conversion of LA to LM, and conversion of LT, LA, and LM would almost reach
      equilibrium after 60 h. The concentration of methanol and the storage time would
      also change the form of the LT when LA, LT, and LM were extracted by methanol
      water in acidic condition. So the determination and separation of LA and LT
      should possibly exclude methanol in acidic condition.

PMID- 20819292
TI  - Development and validation of a fast RP-HPLC method for the determination of
      clobetasol propionate in topical nanocapsule suspensions.
AB  - A simple and rapid high-performance liquid chromatographic method is validated
      for the determination of clobetasol propionate in topical nanocapsule
      suspensions. The method is carried out on an RP-18 column with a mobile phase
      composed of methanol-water (80:20 v/v) and UV detection at 241 nm. The method
      validation yields good results with respect to linearity, specificity, precision,
      accuracy, and robustness. The calibration curve in the range of 5.0-40.0
      microg/mL shows a correlation coefficient of 0.9999. Precision (intra-day and
      inter-day) is demonstrated by a relative standard deviation lower than 1.5%.
      Accuracy is assessed by the recovery test of clobetasol propionate from sample
      matrixes (98.33 +/- 0.88%). In conclusion, the method is suitable to be applied
      to assay clobetasol propionate in topical formulations of polymeric nanocapsules,
      avoiding the use of a buffer solution in the mobile phase.

PMID- 20819293
TI  - Determination of fluticasone propionate in nasal sprays by a validated stability
      indicating MEKC method.
AB  - A micellar electrokinetic chromatography method (MEKC) is developed and validated
      for the analysis of fluticasone propionate (FP) in nasal sprays. The MEKC method
      is performed on a fused-silica capillary (50 mum i.d.; effective length, 40 cm).
      The background electrolyte consists of 25 mM borate and 25 mM anionic detergent
      SDS solution at pH 9. The capillary temperature is maintained at 35 degrees C,
      and the applied voltage is 20 kV. The injection is performed using the
      hydrodynamic mode at 50 mbar for 6 s with detection at 238 nm. The method is
      linear in the range of 2-80 mug/mL (r(2) = 0.9956). The specificity and stability
      indicating capability are proven through forced degradation studies inclusive by
      mass spectrometry, which also shows that there is no interference of the
      excipients. The limit of detection and limit of quantitation are 0.56 and 2
      mug/mL, respectively. Moreover, method validation demonstrates acceptable results
      for accuracy, precision, and robustness. The proposed method was successfully
      applied for the quantitative analysis of FP nasal sprays, and the results were
      compared to a validated reversed-phase liquid chromatographic method, showing non
      significant difference (P > 0.05).

PMID- 20819294
TI  - HPLC-DAD stability indicating determination of nitrofurazone and lidocaine
      hydrochloride in their combined topical dosage form.
AB  - In this work, a simple, rapid, and selective high-performance liquid
      chromatography (HPLC) method with diode array detection was developed for the
      simultaneous determination of nitrofurazone (NZ) and lidocaine hydrochloride
      (LD). The chromatographic separation was achieved by using Zorbax Eclipse XDB
      C(18) (4.6 x 150 mm, 5 mum p.s.) analytical column and a mobile phase composed of
      0.025 M disodium hydrogen phosphate-methanol-triethylamine (70:30:0.1, v/v/v) (pH
      4.0) at a flow rate of 1 mL/min. The detector was set at wavelengths 374 and 220
      nm for NZ and LD, respectively, and quantification of the analytes was based on
      measuring their peak areas. The retention times for NZ and LD were approximately
      4.5 and 5.7 min, respectively. The reliability and analytical performance of the
      proposed HPLC procedure were statistically validated with respect to system
      suitability, linearity, ranges, precision, accuracy, selectivity, robustness, and
      detection and quantification limits. The linear dynamic ranges were 0.5-25 and
      2.5-100 mug/mL for NZ and LD, respectively, with correlation coefficients >
      0.999. The stability-indicating aspects of the proposed method were demonstrated
      by the resolution of the two analytes from the related substance and potential
      impurity (2,6-dimethylaniline) as well as from forced-degradation products. The
      validated HPLC method was successfully extended to the analysis of the combined
      topical dosage form (soluble dressing) where no interfering peaks were
      encountered from the dosage form matrix or the inactive ingredients.

PMID- 20819295
TI  - Development and validation of a selective and rapid LC-MS-MS method for the
      quantification of abacavir in human plasma.
AB  - A simple, precise, and rapid liquid chromatography-tandem mass spectrometry
      method is developed and validated for the quantification of abacavir, a
      nucleoside reverse transcriptase inhibitor. Abacavir and granisetron (internal
      standard) were isolated from 100 muL human plasma by liquid-liquid extraction in
      ethyl acetate and dichloromethane (90:10, v/v). The chromatographic separation is
      achieved on Gemini C(18) analytical column (150 mm x 4.6mm, 5-mum particle size)
      under isocratic conditions at a flow rate of 1.0 mL/min. The parent --> product
      ion transitions for abacavir (m/z 287.2-->191.2) and internal standard (m/z 313.1
      ->138.2) were monitored on a triple quadrupole mass spectrometer operating in the
      multiple reaction monitoring (MRM) and positive ion mode. The linearity of the
      method for abacavir is established in the range of 29.8-9318 ng/mL with an
      analysis time of 2.0 min. Acceptable precision and accuracy were obtained for
      concentrations over the standard curves studied. The mean recovery and process
      efficiency of analyte obtained at three quality control levels was 86.8% and
      87.9%, respectively. The application of this method for routine measurement of
      plasma abacavir concentration is demonstrated by a pharmacokinetic and/or
      bioequivalence study conducted in 28 healthy volunteers for a 300 mg tablet
      formulation under fasting condition.

PMID- 20819296
TI  - Quantification of underivatized fatty acids from vegetable oils by HPLC with UV
      detection.
AB  - We propose a chromatographic method for the separation of saturated and
      unsaturated fatty acids by a high-performance liquid chromatography system,
      equipped with a photo diode array detector. Central to the method is the use of
      an appropriate mobile phase composed of acetonitrile, methanol, and n-hexane in
      ratio 90:8:2 acidified with 0.2% acetic acid, which allows the detection of fatty
      acids without a preliminary derivatization with chromophores or fluorescent dyes.
      Calibration on solutions of standards mixtures gives a quantification limit (at a
      wavelength of 208 nm) of 0.232, 0.093, 0.039, 0.056, 0.068, 0.004, 0.0005, 0.067
      mg/mL for the myristic, palmitic, palmitoleic, stearic, oleic, linoleic,
      linolenic, and erucic acids, respectively. The method, applied to different
      vegetable oils (olive, sunflower, soybean, and palm) was able to distinguish the
      main fatty acids and quantify their amount. Data reliability was tested by
      comparing our results (on the relative percentages of some fatty acids in the
      olive oil) with those obtained by gas chromatographic analysis. Differences of
      the order of 0.3%, 0.6%, 2%, and 6% were observed for the oleic, linoleic,
      palmitic, and linolenic acids. Although less accurate, our method proved to be a
      simple alternative to standard gas chromatographic technique, as it can be
      applied even using a simple UV detector.

PMID- 20819297
TI  - Determination and pharmacokinetics study of beta-lactamase in rat plasma by
      fluorimetric HPLC.
AB  - For the determination of in vivo beta-lactamase activity, a high-performance
      liquid chromatographic (HPLC) method was established, and the pharmacokinetics of
      beta-lactamase after intravenous administration to the rats was analyzed using
      this standardized HPLC method. The plasma samples containing beta-lactamase were
      reacted with ampicillin (substrate) and further processed to make them
      fluorescent. The fluorescent compound of interest was separated using HPLC at
      room temperature using the excitation and the emission wavelengths of 410 nm and
      475 nm, respectively. For the pharmacokinetic studies, 252 mU of beta-lactamase
      solution was administered to the rats through the tail vein injection (n = 6).
      The blood samples were withdrawn from the tail vein at different time points and
      analyzed by HPLC for beta-lactamase activity. For the HPLC method of beta
      lactamase in plasma samples, the peak area showed a good correlation within the
      concentration ranges of 0.126-12.6 mU/mL (10-1000 ng/mL). The coefficients of
      variations were within 0.56-6.24, and the percentage recovery were within 102
      107. After the intravenous injection, plasma concentration at the time zero
      (C(p0)) was 11.47 +/- 0.48 mU/mL, and no beta-lactamase was detected 24 h after
      the injection. The volume of distribution (V(d)) was 22 mL. An elimination half
      life (t(1/2)) of 4.12 +/- 0.5 h and AUC of 79.4 +/- 12.9 mU.hr/mL were also
      calculated. The HPLC fluorimetric method was a very sensitive and reproducible
      method for the detection of beta-lactamase in plasma. The disposition of beta
      lactamase after intravenous administration followed one-compartment and first
      order kinetics.

PMID- 20819298
TI  - HPLC method for quantification of oxidative stress by salicilate hydroxylation in
      human plasma.
AB  - The aim of the present study was to modify and validate a high-performance liquid
      chromatographic (HPLC) method for determining 2,3 and 2,5 dihydroxybenzoic acid
      (2,3-DHBA and 2,5-DHBA) from salicylic acid in human plasma. The mobile phase was
      a mixture of sodium acetate/citrate (pH 2.5) 30 mM-methanol (93:7, v/v). The
      injection volume was 10 muL. Retention time for 2,5-DHBA, and 2,3-DHBA was 4.5 +/
      0.10 and 5.8 +/- 0.15 min, respectively. The detection and quantification limits
      were 10 and 40 nM for 2,3-DHBA and 8 and 20 nM for 2,5-DHBA. Linearity was
      evaluated in the range of 40-1600 nM for both metabolites. Inter- and intra
      analysis variation coefficient was below 10%. Good recoveries of more than 99%
      were obtained for both metabolites using this method.

PMID- 20819299
TI  - Determination of fumonisins in milled corn grains using HPLC-MS.
AB  - A new method for determination of fumonisins in corn samples was developed and
      validated. The mycotoxins were extracted by a mixture of methanol-acetonitrile
      water (1:1:2, v/v/v) and determined on a liquid chromatograph with mass
      spectrometric detection. The separation was performed on Zorbax XDB-C(18) column
      (150 x 4.6 mm; 5 microm) with a Metaguard ODS-2 precolumn (30 x 4.6 mm; 5 mum)
      using gradient elution with mobile phase consisting of acetonitrile and 5 mmol/L
      ammonium acetate (adjusted by acetic acid to pH 3.0). For detection of (M+H(+))
      ions, a quadrupole mass spectrometer in single ion monitoring mode was applied.
      Developed method showed very good linearity in a tested range of concentration.
      Detection limit is 62.0 microg FB(1)/kg and 58.5 microg FB(2)/kg of maize grains.
      Because the detection limits lie under the maximum permitted EU levels, the
      method is suitable for determination of fumonisins in milled corn grains.

PMID- 20819300
TI  - TLC and HPLC methods to follow the synthesis of vinorelbine.
AB  - The thin-layer chromatography (TLC) combined with high-performance liquid
      chromatography (HPLC) has been proved to be a quick and valid method to detect
      the intermediates and the end-product created during the chemosynthesis process
      of vinorelbine (VB). This paper gives a detailed investigation on the results of
      two determination methods when the condition of the detection changed. It shows
      that when TLC developer is consisted of petroleum ether, chloroform, acetone, and
      diethyl amine (23.5:12:2:2.5, v/v/v/v), vinblastine sulfate (VBS),
      anhydrovinblastine (AHVB), and VB can be separated specifically. When the mobile
      phase of HPLC is a mixture of methyl alcohol, acetonitrile, diethyl amine, and
      high purity water (420:252:3:225; v/v/v/v), adjusted with orthophosphoric acid to
      pH 6.5, the intermediates and the resultants of the chemosynthesis of VB can be
      determined effectively. It can also be used to fix quantify of the resultants.
      The calibration curve for VB shows good linearity in the two mass concentration
      ranges of 0.0100-0.0500 mg/mL (r = 0.9956) and 0.00600-0.0100 mg/mL (r = 0.9978),
      respectively. The limit of detection of HPLC for VB is 0.200 microg/mL.

PMID- 20819301
TI  - Preparation and evaluation of silica-based ionic liquid-modified stationary phase
      for HPLC.
AB  - A new high-performance liquid chromatography (HPLC) stationary phase was firstly
      synthesized based on the ionic liquid 2-ethyl-4-methylimidazole chloride. And the
      performances of the resulting stationary phase were determined by Fourier
      transform infrared (FT-IR), thermogravimetric analysis (TGA), and (13)C nuclear
      magnetic resonance (NMR) spectroscopy. The retention characteristics of the
      resulting stationary phase were evaluated by normal phase HPLC conditions to
      separate tanshinone I and tanshinone IIA in Danshen herb. The results
      demonstrated that the synthesized ionic liquid was bond-linked to the silica
      surface successfully and that IL-modified silica is more effective than
      unmodified silica when separating tanshinone I and tanshinone IIA in Danshen
      herb.

PMID- 20819302
TI  - High-performance liquid chromatography analysis of by-products and intermediates
      arising during the synthesis of the acetylcholinesterase reactivator HI-6.
AB  - An high-performance liquid chromatography (HPLC) method for identification of
      quaternary and non-quaternary compounds (parent compounds, intermediates, by
      products, and products) within the synthesis of the acetylcholinesterase
      reactivator HI-6, the most promising antidote of nerve agent poisonings, is
      described. This HPLC method could be of high interest as a quick purity control
      for those who are interested in development of new acetylcholinesterase
      reactivators as well as for those who are interested in the synthesis of HI-6 in
      laboratory or in large-scale production. An HPLC method for quaternary compounds
      without using common ion-pairing reagents was developed, too.

PMID- 20819303
TI  - Primary eye care in sub-Saharan African: do we have the evidence needed to scale
      up training and service delivery?
AB  - The models for addressing the delivery of an eye-care service in sub-Saharan
      Africa have seen considerable revision in the last 30 years, and the on-going
      challenges, as well as the future needs, will probably require many more changes
      and new systems. There is a need to assess the different models that are
      currently employed, in order to ensure that all potential contributions to the
      elimination of avoidable blindness are used; the evolving concept of primary eye
      care (PEC) requires such assessment. For the current review, the published
      literature on eye care provided by general front-line healthworkers was screened
      for articles that provided evidence of the impact of such PEC on the general
      delivery of eye care in sub-Saharan Africa. Of the 103 relevant articles
      detected, only three provided evidence of the effectiveness of PEC and the
      authors of all three of these articles suggested that such eye care was not
      meeting the needs or expectations of the target populations, the trainers, or
      programmes of eye care. Among the main problems identified were a lack of a clear
      definition of the scope of practice for PEC, the need for clarifying the specific
      skills that a front-line healthworker could perform correctly, and the changing
      needs and expectations for the delivery of an eye-care service in Africa. If PEC
      is to become adequately grounded in Africa, the generation of further evidence of
      the effectiveness and limitations of such care would be a prudent move.

PMID- 20819304
TI  - Healthcare-seeking strategies among displaced children in war-ridden northern
      Uganda: the case of malaria.
AB  - A field study was performed to examine suffering and treatment seeking from the
      perspective of children aged 8-16 years living in war-affected northern Uganda.
      Various techniques for collecting qualitative and quantitative data were used,
      including a semi-structured questionnaire about illness experiences and medicine
      use over a 1-month recall period. The 165 children who were interviewed were
      attending primary schools for displaced children and/or commuters' night
      shelters. The children frequently attributed their common febrile ailments to
      malaria and used a variety of pharmaceuticals and herbal remedies, as self
      medication, for their self-diagnosed malarial episodes. Misdiagnosis of febrile
      illnesses by the children (as well as by the local healthcare providers) and
      frequent misuse of medicines in the treatment of these illnesses appeared to be
      very common. Improvement of the health conditions of these children requires a
      change of focus. Firstly, children above the age of 5 years who are not under
      adult care and who are often no longer welcome in the local hospital's paediatric
      ward need to be accepted at the outpatient clinics currently intended for adults.
      Secondly, the local diagnostic system needs to be improved, not only so that
      malaria can be reliably diagnosed but also so that alternative diagnoses can be
      confirmed or rejected, otherwise the current over-consumption of antimalarial
      drugs may simply be replaced with an over-consumption of antibiotics.

PMID- 20819305
TI  - The changing profile of cutaneous leishmaniasis in a focus of the disease in
      Jahrom district, southern Iran.
AB  - Human cutaneous leishmaniasis (CL) is endemic in several parts of Iran, and there
      is an urban focus of the disease in the district of Jahrom, which forms part of
      the southern province of Fars. To explore the current profile of the disease in
      Jahrom district, samples were taken from the skin lesions of 40 cases of CL
      patients in the district, so that the causative parasites could be identified, to
      species, in a nested PCR. Although Leishmania tropica has been identified, in the
      past, as the cause of most of the urban CL in Fars province, the predominant
      species represented in the recent samples from Jahrom district was L. major
      (87.5%), while L. tropica was relatively rare (12.5%). More than one in every
      three (35%) of the cases examined was a child aged <10 years. The most common
      location of the skin lesions was on the hands. Although most of the cases had one
      skin lesion each, two cases each had >25 such lesions. The change in the
      predominant parasite causing CL in Jahrom district, from the L. tropica usually
      associated with the urban disease in Iran to the L. major more usually associated
      with CL in rural settings, may well necessitate changes in the local strategies
      for the prevention and control of CL.

PMID- 20819306
TI  - Mass infection with Entamoeba histolytica in a Japanese institution for
      individuals with mental retardation: epidemiology and control measures.
AB  - After two cases of amoebic colitis were detected at an institution for the
      mentally retarded in the Yamagata prefecture of Japan, the prevalence and
      epidemiology of Entamoeba histolytica infection at the institution were
      investigated. When the 76 residents with mental retardation were checked by
      serology and stool examinations, 40 (53%) showed evidence of infection with E.
      histolytica (i.e. E. histolytica-specific antibodies in their serum, Entamoeba
      cysts in their stools, and/or E. histolytica-specific antigens in their stools).
      The cysts were all assumed to be those of E. histolytica since all nine of the 18
      cyst-positive stool samples investigated using a PCR (that distinguishes E.
      histolytica from E. dispar) were found positive for this species. The E.
      histolytica found in the institution in Yamagata appears to have been brought
      into the institution, from a similar institution in Kanagawa prefecture, by a
      mentally retarded individual who relocated from Kanagawa to Yamagata. Isolates of
      E. histolytica recovered during an outbreak in the institution in Kanagawa appear
      genotypically identical to the genotyped isolates collected in the outbreak
      investigated in the present study. The 40 infected individuals in Yamagata were
      each treated for 10 days with metronidazole or diloxanide furoate. The residents
      and staff of the institution were encouraged to wash their hands more frequently
      and more thoroughly, and the staff were asked to clip residents' fingernails and
      to improve the cleanliness/sterilization of the surfaces in the institution that
      were most likely to be contaminated with E. histolytica (lavatories, handrails,
      doors, doorknobs, washrooms, clothing etc). In the last 5 years of follow-up
      since the instigation of these and other infection-control measures, and the last
      treatments, no cases of E. histolytica infection have been found in the
      institution. This encouraging result offers hope and guidance to those attempting
      to control outbreaks of E. histolytica infection in other institutions.

PMID- 20819307
TI  - Antiprotozoal activities of some constituents of Markhamia tomentosa
      (Bignoniaceae).
AB  - Phytochemical investigation of an ethyl-acetate extract of the stem bark of
      Markhamia tomentosa (Bignoniaceae), which had good antimalarial activity in
      vitro, resulted in the isolation of eight known compounds: 2-acetylnaphtho[2,3
      b]furan-4,9-dione (1), 2-acetyl-6-methoxynaphtho[2,3-b]furan-4,9-dione (2),
      oleanolic acid (3), pomolic acid (4), 3-acetylpomolic acid (5), tormentic acid
      (6), beta-sitosterol (7) and beta-sitosterol-3-O-beta-D-glucopyranoside (8). The
      structures of these compounds were established by spectroscopic methods. Each of
      compounds 1, 2, 4 and 5 was evaluated in vitro for its antiprotozoal activities
      against the ring stages of two chloroquine-resistant strains of Plasmodium
      falciparum (K1 and W2), the amastigotes of Leishmania donovani, and the
      bloodstream trypomastigotes of Trypanosoma brucei rhodesiense (the species
      responsible for human malaria, visceral leishmaniasis and African
      trypanosomiasis, respectively). Although compounds 1 and 2 exhibited potent
      antiprotozoal activities, they also showed high toxicity against a mammalian (L
      6) cell line.

PMID- 20819308
TI  - Gene cloning, expression and serological evaluation of the 12-kDa antigen-B
      subunit from Echinococcus granulosus.
AB  - A 12-kDa subunit of antigen B from Echinococcus granulosus has recently been
      cloned, expressed and used in diagnostic ELISA to test human sera for evidence of
      cystic echinococcosis. The performance of the ELISA based on the recombinant
      antigen (rAgB) was compared with that of similar assays based on native antigen B
      (nAgB) or hydatid-cyst fluid. For the preparation of the rAgB, total RNA was
      extracted from Ec. granulosus protoscoleces so that antigen-B complementary DNA
      could be synthesised, amplified by PCR, and then cloned into the pQE30 expression
      vector. The recombinant plasmid was transformed in Escherichia coli and induced
      using isopropyl-beta-D-thiogalactopyrano-side. Bacterial samples were collected,
      lysed and then analysed by SDS-PAGE and western blotting. The recombinant protein
      was purified by affinity chromatography. Although the performance of the ELISA
      based on cyst fluid appeared identical to that of the assay based on the
      recombinant antigen (with a sensitivity, specificity, positive predictive value
      and negative predictive value of 96.0%, 97.0%, 97.2% and 95.5%, respectively),
      the corresponding results for the ELISA based on nAgB (98.6%, 100%, 100% and
      98.5%) were slightly better. Despite this difference (which was not statistically
      significant), the comparative ease with which large quantities of the recombinant
      antigen could be produced make the antigen a potentially useful tool in the
      diagnosis of cystic echinococcosis.

PMID- 20819309
TI  - Factors associated with urinary schistosomiasis in two peri-urban communities in
      south-western Nigeria.
AB  - In Nigeria, there is only very limited epidemiological information on which the
      control of human urinary schistosomiasis could be based. In a cross-sectional
      study, therefore, the prevalences and intensities of, and risk factors for, human
      infection with Schistosoma haematobium infection were explored in two endemic
      peri-urban villages in the south-western state of Osun. The villagers' knowledge
      about the infection and demographic, socio-economic and environmental variables
      were recorded using a structured questionnaire. Of the 1023 individuals who were
      investigated, 634 (62.0%) were found infected, with a mean (S.D.) overall
      intensity of 114.2 (327.7) eggs/10 ml urine. The subjects aged 10-14 years had
      both the highest prevalence (83.6%) and the highest mean (S.D.) intensity of
      infection [196.67 (411.7) eggs/10 ml urine]. Most (70.0%) of the subjects
      appeared to have no knowledge of the transmission of S. haematobium. The results
      of multivariate regression analysis indicated that infection and moderate-heavy
      infection (i.e. >50 eggs/10 ml urine) were both associated with: a low family
      income, of <U.S.$500/month [with adjusted odds ratios (aOR) of 3.72 and 3.35,
      respectively], the number of children aged 10-15 years living in the household
      (with aOR of 1.60 and 1.99, respectively), not living with biological parents
      (with aOR of 1.93 and 5.21, respectively), and living close to (i.e. within a 30
      min walk of) the local river (with aOR of 1.38 and 1.61, respectively). Literacy
      of the family head was, however, a protective factor (with corresponding aOR of
      0.28 and 0.30, respectively). Human urinary schistosomiasis appears to be highly
      endemic in peri-urban/rural Nigeria and closely associated with poverty. To
      reduce the transmission of S. haematobium in endemic communities, health
      education that is not only of high quality but also culturally sensitive is
      needed.

PMID- 20819310
TI  - The stigmata and discrimination experienced, in southern India, by cases of
      lymphatic filariasis.
AB  - Between November 2006 and November 2009, the stigmata and discrimination
      experienced by 201 cases of lymphatic filariasis (LF) living in three areas of
      the southern Indian state of Tamil Nadu (the Pondicherry urban agglomeration and
      two, endemic, rural villages in Villupuram district) were investigated in
      interviews. The narratives of nine of the interviewees are reported here in
      detail, to bring to light the various domains of life in which LF cases are
      stigmatized and discriminated against. Lymphatic filariasis can, and often does,
      adversely affect each case's livelihood, marital prospects, and social and
      marital life and can also diminish the marital prospects of a case's children.
      The deformity caused by the disease and the incapacitation resulting from the
      often-frequent attacks of adenolymphangitis appeared to be the main reasons for
      the stigmatization and discrimination. Although morbidity control is one of the
      'twin pillars' of the Global Programme for Elimination of Filariasis, the
      stigmata and discrimination associated with such morbidity also need to be
      addressed.

PMID- 20819311
TI  - High-resolution melt-curve analysis of random amplified polymorphic DNA (RAPD
      HRM) for the characterisation of pathogenic leptospires: intra-serovar
      divergence, inter-serovar convergence, and evidence of attenuation in Leptospira
      reference collections.
AB  - High-resolution melt-curve analysis of random amplified polymorphic DNA (RAPD
      HRM) is a novel technology that has emerged as a possible method to characterise
      leptospires to serovar level. RAPD-HRM has recently been used to measure intra
      serovar convergence between strains of the same serovar as well as inter-serovar
      divergence between strains of different serovars. The results indicate that intra
      serovar heterogeneity and inter-serovar homogeneity may limit the application of
      RAPD-HRM in routine diagnostics. They also indicate that genetic attenuation of
      aged, high-passage-number isolates could undermine the use of RAPD-HRM or any
      other molecular technology. Such genetic attenuation may account for a general
      decrease seen in titres of rabbit hyperimmune antibodies over time. Before RAPD
      HRM can be further advanced as a routine diagnostic tool, strains more
      representative of the wild-type serovars of a given region need to be identified.
      Further, RAPD-HRM analysis of reference strains indicates that the routine
      renewal of reference collections, with new isolates, may be needed to maintain
      the genetic integrity of the collections.

PMID- 20819312
TI  - Management of snakebites by the staff of a rural clinic: the impact of providing
      free antivenom in a nurse-led clinic in Meserani, Tanzania.
AB  - In Tanzania, the impact, on clinical outcomes and treatment-seeking behaviour, of
      a rural, nurse-led clinic that provides free, antivenom-based treatment of
      snakebite envenomation was recently assessed. Data on all 85 patients who,
      between April 2007 and the end of 2009, received treatment for snakebite
      envenomation at the Snake Park clinic in Meserani, Tanzania, were collected
      prospectively. Although only four cases of snakebite envenomation were treated in
      the last 9 months of 2007, 34 such cases were treated in 2008 and 47 in 2009. The
      85 snakebite cases had a mean age of 23 years and a male:female ratio of 1.4.
      Most of the bites occurred in the evening or at night and most also occurred
      during the rainy season. In some cases, the seeking of treatment from traditional
      healers delayed treatment at the clinic. After being bitten, the snakebite cases
      travelled a mean of 82 km (range=2-550 km) to reach the clinic. Thirty-two (37%)
      of the cases were each unable to identify the snake that had bit them. Of the
      bites in which the snake was identified, the puff adder (Bitis arietans) caused
      more (24) than any other snake. Forty-two of the snakebite cases received
      antivenom. Only one patient (1%), a 12-year-old girl, was believed to have died
      as the result of a snakebite but another six (7%) each required a skin graft or
      the amputation of a limb or digit. Establishment of the Snake Park clinic appears
      to have improved access to snakebite treatment, with cases of snakebite
      travelling long distances to reach the clinic (because of the lack of any other
      source of antivenom in Tanzania). Although the clinic is nurse-led, treatment
      outcomes among the snakebite victims who attend the clinic appear to be good.

PMID- 20819313
TI  - Elevated levels of urinary hyaluronidase in humans infected with intestinal
      parasites.

PMID- 20819314
TI  - Clinical characteristics of oral tolerance induction of IgE-mediated and non-IgE
      mediated food allergy using interferon gamma.
AB  - Food allergies are classified as IgE-mediated food allergies (IFAs) and non-IgE
      mediated food allergies (NFAs). Recently, oral immunotherapy (OIT) has been found
      to be successful for treating both IFA and NFA, especially using interferon (IFN)
      gamma. This study was designed to clarify the clinical characteristics of IFA and
      NFA and compare the therapeutic characteristics of OIT using subcutaneously
      administered IFN-gamma for both types of food allergy. In this study, 148
      patients were categorized into the IFA and NFA group following food challenge,
      skin-prick test and food-specific IgE tests. The patients were then treated using
      protocols specific for IFA and NFA using subcutaneous IFN-gamma injection as a
      randomized controlled trial. The principle of complete allergy resolution at
      prior dose in the case of IFA was also evaluated. Only the patients with IFA and
      NFA treated with OIT using IFN-gamma achieved tolerance successfully. Tolerance
      was achieved from low-dose range in IFA and in high-dose range for NFA. Complete
      tolerance was not obtained without achieving complete allergy resolution at each
      dose of the allergen before increasing the dosage in IFA. Both IFA and NFA can be
      successfully treated with OIT using IFN-gamma but show different clinical and
      therapeutic characteristics. IFN-gamma is necessary for the tolerance induction
      but not for tolerance maintenance. Additional study for the mechanisms of
      tolerance induction by IFN-gamma is needed.

PMID- 20819315
TI  - Impact of delay in asthma diagnosis on health care service use.
AB  - Delays in diagnosing asthma in children are common and are known to delay asthma
      specific treatment. Few studies have investigated whether a delay in asthma
      diagnosis impacts the use of health care services. This study was designed to
      assess whether a delay in diagnosis of asthma influences the use of health care
      services. This was a retrospective cohort study with subjects elicited from a
      convenience sample of 839 healthy children. The criteria for asthma was met in
      276 (33%) subjects; of these subjects 179 (65%) had a delay in the diagnosis of
      asthma and 97 (35%) had a timely diagnosis. Data on health care services (e.g.,
      flu shot, availability of a peak flow meter, hospitalizations, and urgent care or
      emergency department visits) and the frequency of systemic steroid treatments
      were collected from medical records during the first 18 years of life. The
      frequencies of health service and use of systemic steroids were compared using
      Poisson and logistic regression models in asthmatic children with and without a
      delay in asthma diagnosis. Children with a delay in asthma diagnosis were more
      likely to visit urgent care centers at least once (40.8% versus 21.6%; p <
      0.001), compared with those with a timely diagnosis. There were no significant
      differences in other health care service or systemic steroid use. A delay in the
      diagnosis of asthma was associated with an increase in urgent care visits
      suggesting suboptimal care. Clinicians should be aware that a delay in the
      diagnosis of asthma in children may result in the use of suboptimal health care
      services.

PMID- 20819316
TI  - Factors associated with allergic rhinitis in children and adolescents from
      northern Mexico: International Study of Asthma and Allergies in Childhood Phase
      IIIB.
AB  - The epidemiology of allergic diseases has not been studied extensively in Mexico.
      The present study, based on the International Study of Asthma and Allergies in
      Childhood Phase IIIB survey, reports the prevalence of allergic rhinitis and the
      associated risk factors in the pediatric population in four cities in northern
      Mexico. Children (6-7 years old) and adolescents (13-14 years old) in public
      elementary and secondary schools were surveyed in 2002 and 2003. The subjects
      were chosen randomly from Ciudad Victoria, Mexicali, Monterrey, and Tijuana. The
      following categories were analyzed: occurrence of rhinitis symptoms (currently or
      in the last 12 months), rhinoconjunctivitis symptoms, a previous diagnosis of
      allergic rhinitis, and relevant environmental factors. Factors associated with
      rhinitis that were identified previously with the chi-squared test were analyzed
      using logistic regression. The number of valid questionnaires was 10,892 for
      schoolchildren and 12,299 for adolescents. In 6- to 7-year-old children, the
      following frequencies were determined: rhinitis (ever), 27.9%; current rhinitis,
      24.2%; rhinoconjunctivitis, 9.2%; and diagnosis of allergic rhinitis, 5.5%. The
      corresponding frequencies in 13- to 14-year-old children were 33.3, 34.1, 18.4,
      and 3.8%. In both 6- to 7-year-old and 13- to 14-year-old children, all rhinitis
      items were associated with asthma symptoms, dermatitis symptoms, paracetamol
      consumption, and maternal smoking (odds ratio, >1; p < 0.05). The main risk
      factors associated with allergic rhinitis symptoms in children and adolescents
      from cities in northern Mexico were other allergic conditions, paracetamol
      consumption, and passive smoking.

PMID- 20819317
TI  - The usefulness of biomarkers of airway inflammation in managing asthma.
AB  - The goal of managing asthma is to maintain disease control. Current approaches to
      assessment of control do not include measurement of airway inflammation. This
      study was designed to assess the usefulness of biomarkers of airway inflammation
      in guiding asthma management decisions. A literature review was performed.
      Bronchial biopsy is a direct measure of airway inflammation but not practical for
      routine use. Enumeration of sputum eosinophils is very useful in guiding changes
      in controller medication to decrease asthma exacerbations, whereas measurement of
      exhaled nitric oxide has not proven to be useful in this regard. Serial
      measurement of airway hyperreactivity as a guide to asthma management yields
      inconclusive results. Use of indirect stimuli for bronchial challenge offers both
      practical and theoretical advantages in the assessment of airway hyperreactivity.
      Data on the analysis of exhaled breath condensate have not yet been studied
      adequately in guiding management decisions. Enumeration of sputum cell counts
      appears to be the most useful biomarker of airway inflammation in guiding asthma
      management decisions. Combined approaches using simple methods of measuring
      airway hyperreactivity and obtaining sputum samples hold promise for the future,
      particularly if rapid analysis of cellular products in sputum can be developed.

PMID- 20819318
TI  - Safety and tolerability of levocetirizine dihydrochloride in infants and children
      with allergic rhinitis or chronic urticaria.
AB  - Allergic rhinitis (AR) and chronic idiopathic urticaria (CIU) are common causes
      of substantial illness and disability in preschool children. Antihistamines are
      commonly used to treat preschool children with these conditions, but their use is
      based mostly on extrapolated efficacy from adult populations; it is thus
      important to characterize the safety of antihistamines in the pediatric
      population. This study was designed to assess the safety of levocetirizine
      dihydrochloride oral liquid drops in infants and children with AR or CIU. Two
      multicenter, double-blind, randomized, parallel-group studies randomized infants
      aged 6-11 months (study 1, n = 69) and children aged 1-5 years (study 2, n = 173)
      to levocetirizine, 1.25 mg (q.d. or b.i.d., respectively), or placebo for 2
      weeks, using a 2:1 ratio. Safety evaluations included treatment-emergent adverse
      events (TEAEs), vital signs, electrocardiographic (ECG) assessments, and
      laboratory tests. The overall incidence of TEAEs was similar between
      levocetirizine and placebo in both studies. Most TEAEs were mild or moderate in
      intensity. TEAEs prompted discontinuation of therapy in three patients receiving
      levocetirizine in study 1. No clinically relevant changes from baseline in vital
      signs or laboratory parameters were apparent in either study; changes from
      baseline in these evaluations were similar between groups. No significant changes
      were observed in ECG parameters, including corrected QT interval. Levocetirizine,
      1.25 and 2.5 mg/day, was well tolerated in infants aged 6-11 months and in
      children aged 1-5 years, respectively, with AR or CIU.

PMID- 20819319
TI  - Efficacy of oral olopatadine hydrochloride for the treatment of seasonal allergic
      rhinitis: A randomized, double-blind, placebo-controlled study.
AB  - Adequate treatment is critical for maintaining a good level of quality of life
      (QOL) during the pollen season in patients suffering from seasonal allergic
      rhinitis (SAR). Olopatadine, a histamine H(1)-receptor antagonist, has been
      approved in the United States and Europe for the treatment of AR and allergic
      conjunctivitis as a nasal spray and an ophthalmic solution, respectively. We
      conducted a randomized, double-blind, placebo-controlled study to determine
      whether orally administered olopatadine for prophylactic purposes might also be
      effective for the control of nasal allergy symptoms, especially nasal congestion,
      in patients with SAR due to Japanese cedar pollen (SAR-JP). A total of 110
      patients with SAR caused by JP were randomized to the treatment. The subjects
      recorded their nasal and ocular allergic symptom scores in a diary, and their QOL
      was assessed by the Japanese version of the Rhinoconjunctivity Quality of Life
      Questionnaire. Treatment with oral olopatadine significantly suppressed sneezing
      (p < 0.001), rhinorrhea (p < 0.001), and nasal congestion (p < 0.05). The total
      QOL score during the peak JP season was superior in the olopatadine group than in
      the placebo group (p < 0.05). However, orally administered olopatadine did not
      exert any significant effect against eye itching and watering of the eyes, unlike
      olopatadine nasal spray. Treatment with olopatadine tablets yielded superior QOL
      scores in the domains of usual daily activities and outdoor activities when
      compared with placebo. No serious adverse effects of the treatment were reported
      during the study period. These results suggest that oral olopatadine treatment
      may be a useful alternative treatment strategy for AR.

PMID- 20819320
TI  - Epinephrine auto-injector use and demographics in a Veterans Administration
      population.
AB  - The epinephrine auto-injector has been widely used over a long period of time.
      Certain aspects of this therapy and demographic data, however, have not been well
      studied. This study investigates patient use and understanding of epinephrine
      auto-injector use. As part of an ongoing quality assurance program, we evaluated
      66 patients who had been given an epinephrine auto-injector and followed in the
      Allergy and Immunology Clinics at the West Los Angeles Veterans Medical Center.
      Data analyzed included patient demographics, medical indications for epinephrine
      auto-injector prescriptions, and the patient's understanding and use of the
      device. The mean age of our patients was 50 years. There were 44 men (66.7%) and
      22 women (33%). Twenty-three patients were prescribed epinephrine auto-injector
      for adverse food reactions. Ninety-two percent (92%) of the patients knew how to
      use their epinephrine auto-injector properly, however, only 58% carried their
      device with them consistently. Of the patients, 91% understood why the auto
      injector was prescribed. Of the total patients prescribed epinephrine auto
      injector, 79% refilled their medication before the 1 year expiration date. Only
      12% of the patients studied had required the use of their auto-injector. Most
      patients knew how and when to administer their epinephrine auto-injector. Despite
      detailed instructions in a specialty clinic only a slight majority carried it
      consistently. These data clearly indicate that further patient education or other
      measures are needed to improve compliance and effective use.

PMID- 20819321
TI  - Repeat epinephrine treatments for food-related allergic reactions that present to
      the emergency department.
AB  - To date, there are sparse data on epinephrine treatment for food-related
      anaphylaxis in adults. We sought to establish the frequency of more than one
      epinephrine treatment for adult patients who present with food-related
      anaphylaxis to the emergency department (ED). We performed a chart review, at two
      academic centers, of all adults presenting to the ED for food allergy (ICD9CM
      codes 693.1, 995.0, 995.1, 995.3, 995.7, 995.60-995.69, 558.3, 692.5, and 708.X)
      between January 1, 2001 and December 31, 2006. We focused on causative foods;
      treatments, including the number of epinephrine treatments given before and
      during the ED visit; and disposition. Through random sampling and appropriate
      weighting, the 486 reviewed cases represented a study cohort of 1286 patients.
      The median age was 36 years and the cohort was 62% women. Shellfish (23%),
      peanuts (12%), tree nuts (14%), and fish (14%) provoked the allergic reaction
      most commonly. Most patients (62%; 95% confidence interval [CI], 57-68%) met
      criteria for food-related anaphylaxis. In the ED, anaphylaxis patients received
      epinephrine (18%), antihistamines (91%), corticosteroids (81%), and inhaled
      albuterol (19%). Overall, 17% (95% CI, 9-25%) of patients with food-related
      anaphylaxis given epinephrine received >1 dose over the course of their reaction.
      Among anaphylaxis patients admitted to the hospital, only 10% included
      anaphylaxis in the discharge diagnosis. At ED discharge (82% of patients), 18%
      were referred to an allergist and 39% were prescribed self-injectable
      epinephrine. Among ED patients with food-related anaphylaxis treated with
      epinephrine, 17% were given >1 dose. This study supports the recommendation that
      patients at risk for food-related anaphylaxis should carry 2 doses of
      epinephrine.

PMID- 20819322
TI  - Reduced clinic, emergency room, and hospital utilization after home environmental
      assessment and case management.
AB  - Allergists often suspect home environmental conditions are contributors to
      allergic disease. Case management can be an effective tool in managing asthmatic
      patients. To describe the impact of home environmental assessments and case
      management on the medical care utilization of patients with allergic disease the
      following studies were conducted. This study was designed to retrospectively
      examine health care utilization of pediatric patients that had a home
      environmental assessment recommended by a pediatric allergist as part of a
      comprehensive case management program. Subjects were chosen from pediatric
      patients who received home assessment after referral for case management by
      pediatric allergy specialists in a hospital-based clinic as indicated by high
      emergency room (ER) and hospital utilization. Case management included education,
      clinic visits, environmental assessment, and a single person responsible for
      following the subject's care. Home assessment included airborne spore
      collections, surface collections, and dust collection for evaluation of antigens.
      There were 25 subjects. Seventy-two percent were asthmatic and 12% were diagnosed
      with allergic rhinitis. In the year before entering the study these subjects
      experienced 47 ER visits, 22 hospitalizations, and 279 clinic visits. In the
      subsequent year they underwent 18 ER visits, 3 hospitalizations, and 172 clinic
      visits. Penicillium/Aspergillus levels were above 100 spores/m(3) of air in 94%
      of homes and above 1000 spores/m(3) in 74% of homes. Thirty-six percent of homes
      had Stachybotrys above 100 spores/m(3). Home environmental assessment and case
      management may reduce medical care utilization for children suffering from
      allergic rhinitis and asthma.

PMID- 20819323
TI  - Efficacy of immunotherapy for treatment of allergic asthma in children.
AB  - Asthma is the most common chronic disease of childhood. Specific immunotherapy is
      widely used in several countries for managing allergic asthma. Many clinical
      trials and a meta-analysis of several studies support its efficacy to reduce the
      symptoms and medical requirements. The purpose of this study was to clarify the
      efficacy of subcutaneous immunotherapy (SCIT) in improving the symptoms and
      reducing medication requirements in primary school children with asthma in
      comparison with pharmacotherapy. A single-blind, drug-controlled clinical trial
      was performed. A total of 242 primary school children with allergic asthma were
      included in the study. The patients were recruited from subjects attending the
      Allergic Center in Mosul City. Their age range was 7-12 years with mean age of 10
      +/- 2 years. From the total only 197 children (81%) completed the study and were
      eligible for analysis, of those, 85 children were managed with SCIT and 112
      children were managed with pharmacotherapies only. The follow-up after 1 year
      indicated that the children treated with SCIT show a marked reduction in the
      clinical symptoms, medication requirements, and the level of serum-specific IgE
      when compared with children treated with conventional drugs. SCIT was effective
      treatment and can prevent or decrease the onset of new sensitization to the
      offending allergen and maintain its beneficial effect for years after
      discontinuation.

PMID- 20819324
TI  - Randomized, double-blind, placebo-controlled trial of acetaminophen for
      preventing mood and memory effects of prednisone bursts.
AB  - Corticosteroids are commonly associated with changes in mood, memory, and the
      hippocampus. Declarative memory decline occurs rapidly after corticosteroid
      administration. Minimal research has focused on interventions to prevent or
      reverse corticosteroid effects on the human brain and associated adverse
      psychiatric effects. Acetaminophen has neuroprotective properties in animal
      models. We examined acetaminophen add-on therapy in patients prescribed
      corticosteroids. Thirty outpatients prescribed oral high-dose prednisone therapy
      for asthma (n = 28) or allergic rhinitis (n = 2) were randomized to approximately
      7 days of acetaminophen (4000 mg/day) or placebo in a double-blind fashion at the
      same time as prednisone. Mood was assessed with the Hamilton Rating Scale for
      Depression, Young Mania Rating Scale, and Activation subscale of the Internal
      State Scale. Memory was assessed with the Rey Auditory Learning Test and asthma
      symptoms with the Asthma Control Questionnaire. Between-group differences were
      assessed using mixed ANCOVAs and within-group changes were examined with paired t
      tests. Baseline mean depression scores were elevated. In the total sample,
      depressive and asthma symptoms improved significantly, while declarative memory
      worsened during prednisone therapy. No between treatment-group differences were
      found in mood or memory measures. Change in asthma symptoms with receiving
      prednisone was not related to change in mood or memory. Prednisone therapy was
      associated with a reduction in depressive symptom severity and decline in
      declarative memory that was not related to changes in asthma symptoms. This is
      consistent with prior research suggesting that prednisone impairs memory and may
      have antidepressant properties. Acetaminophen did not attenuate corticosteroid
      induced mood or memory changes.

PMID- 20819325
TI  - Important Florida botanical aeroallergens.
AB  - Florida is home to approximately 4 million allergy sufferers and almost 15,000
      individual species of plants. Only a few of these plants produce pollen with
      documented allergenicity via in vivo/in vitro testing and provocation challenges.
      Many plant species with proven allergenicity are present only to a limited
      degree. Furthermore, allergenic plants in Florida do not follow the same
      pollinating patterns as the rest of the country, i.e., trees in the spring,
      grasses in the summer, and weeds in the fall. Media outlets that report pollen
      counts to the general public may mislead patients without appropriate
      interpretation. This review highlights clinical studies that document the
      allergenicity of some pollens and summarizes expert opinion regarding other
      prevalent and allergenic pollens throughout the state.

PMID- 20819326
TI  - Atmospheric pollen count in Monterrey, Mexico.
AB  - There are few reports of pollen count and identification in Mexico; therefore, it
      is important to generate more information on the subject. This study was designed
      to describe the prevalence of pollen in the city of Monterrey, Mexico, during the
      year 2004. Atmospheric pollen was collected with a Hirst air sampler, with an
      airflow of 10 L/minute during 2004. Pollen was identified with light microscopy;
      the average monthly pollen count as well as total was calculated from January
      2004 to January 2005. The months with the highest concentration of pollen were
      February and March (289 and 142 grains/m(3) per day, respectively), and July and
      November had the lowest concentration (20 and 11 grains/m(3) per day,
      respectively). Most of the pollen recollected corresponded to tree pollen (72%).
      Fraxinus spp had the highest concentration during the year (19 grains/m(3) per
      day; 27.5% of the total concentration of pollen). Tree pollen predominated from
      January through March; with Fraxinus spp, Morus spp, Celtis spp, Cupressus spp,
      and Pinus spp as the most important. Weed pollen predominated in May, June, and
      December and the most frequently identified, were Amaranthaceae/Chenopodiaceae,
      Ambrosia spp, and Parietaria spp. The highest concentration of grass pollen was
      reported during the months of May, June, September, October, and December with
      Gramineae/Poaceae predominating. Tree pollen was the most abundant during the
      year, with the ash tree having the highest concentration. Weed and grass pollen
      were perennial with peaks during the year.

PMID- 20819327
TI  - DNA repair gene XRCC1 polymorphisms and the risk of asthma in a Turkish
      population.
AB  - Polymorphisms have been identified in several DNA damage repair genes. These
      polymorphisms may effect DNA repair capacity and modulate asthma susceptibility.
      In this study, we aimed to determine the two polymorphisms in DNA repair gene, x
      ray repair cross-complementing group 1 (XRCC1), in a sample of Turkish patients
      with asthma, and evaluate their association with asthma development. We used
      polymerase chain reaction (PCR) and restriction fragment length polymorphism
      (RFLP) to analyze XRCC1 Arg194Trp and XRCC1 Arg399Gln polymorphisms in 116
      patients with asthma and in 180 disease-free controls. Our data showed a positive
      association between the polymorphisms of codons 194 (odds ratio [OR] = 1.97, 95%
      confidence interval [CI] = 1.06-3.66, and p = 0.03 for Arg/Trp genotype) and 399
      (OR = 1.87, 95% CI = 1.12-3.13, and p = 0.02 for Arg/Gln genotype, and OR = 2.59,
      95% CI = 1.24-5.43, and p = 0.01 for Gln/Gln genotype) and asthma risk. No
      statistically significant difference was found for the allelic and genotypic
      distributions of the polymorphisms in XRCC1 gene between mild and moderate
      asthmatic patients. A combined analysis of the effect of XRCC1 codons 194 and 399
      revealed the highest risk (OR = 4.17, 95% CI = 1.77-9.83, and p = 0.001) for
      carriers of the polymorphic alleles in both of these codons. These results
      suggest that the risk of asthma may be associated with DNA repair mechanisms, and
      understanding these mechanisms will help identify individuals at increased risk
      of developing asthma and should lead to improved treatment of asthma.

PMID- 20819328
TI  - A 41-year-old male with cough, wheeze, and dyspnea poorly responsive to asthma
      therapy.
AB  - Reactive airway disease is often triggered by an upper respiratory viral
      infection and readily responds to anti-inflammatory and bronchodilator therapy.
      The differential diagnosis for unresponsive disease includes poorly controlled
      asthma, noncompliance with medical regimen, vocal cord dysfunction,
      rhinosinusitis, gastroesophageal reflux disease or recurrent aspiration, foreign
      body aspiration, allergic bronchopulmonary aspergillosis, Churg-Strauss
      vasculitis, cardiac disorders such as congestive heart failure or mitral
      stenosis, or other pulmonary disorders such as chronic obstructive pulmonary
      disease, alpha-1 antitrypsin deficiency, interstitial lung disease,
      bronchiectasis, sarcoidosis, hypersensitivity pneumonitis, pulmonary embolism,
      cystic fibrosis, airway neoplasms, or laryngotracheomalacia. As is often the
      case, a meticulous history can expeditiously direct the clinician to the
      diagnosis, especially in a patient without a smoking, asthmatic, or atopic
      history.

PMID- 20819329
TI  - Nicorandil ulcer: moves beyond the mucosa.
AB  - The management of wounds is a specialty in its infancy. Success requires more
      than the use of dressings. All wounds require a diagnosis, a point well
      illustrated by the management of these cases which depended solely on stopping
      nicorandil.

PMID- 20819330
TI  - Healthcare associated infection: novel strategies and antimicrobial implants to
      prevent surgical site infection.
AB  - This report is based on a Hygienist Panel Meeting held at St Anne's Manor,
      Wokingham on 24-25 June 2009. The panel agreed that greater use should be made of
      antiseptics to reduce reliance on antibiotics with their associated risk of
      antibiotic resistance. When choosing an antiseptic for clinical use, the
      Biocompatibility Index, which considers both the microbiocidal activity and any
      cytotoxic effects of an antiseptic agent, was considered to be a useful tool. The
      need for longer and more proactive post-discharge surveillance of surgical
      patients was also agreed to be a priority, especially given the current growth of
      day-case surgery. The introduction of surgical safety checklists, such as the
      World Health Organization's Safe Surgery Saves Lives initiative, is a useful
      contribution to improving safety and prevention of SSIs and should be used
      universally. Considering sutures as 'implants', with a hard or non-shedding
      surface to which micro-organisms can form biofilm and cause surgical site
      infections, was felt to be a useful concept.

PMID- 20819331
TI  - Management of osteoarthritis of the knee.

PMID- 20819332
TI  - Diverticular fistulation is associated with nicorandil usage.
AB  - INTRODUCTION: We observed that a number of patients presenting to our clinic with
      diverticular fistulation were taking nicorandil for angina. Recognised side
      effects of nicorandil include gastrointestinal and genital ulceration. The aim of
      our study was to determine whether nicorandil is an aetiological agent in
      diverticular fistulation. PATIENTS AND METHODS: We conducted a case-control study
      of patients with diverticular disease related enteric fistulae. Two patient
      groups were identified: a study group of patients with diverticular fistulae, and
      a control group with uncomplicated diverticular disease. The proportion of
      patients who had ever used nicorandil was compared between the two groups.
      RESULTS: A total of 153 case notes were analysed, 69 patients with fistulae and
      84 control patients with uncomplicated diverticular disease. Female to male ratio
      in both groups was 2:1. The mean age was 71 years in the fistula group and 69
      years in the control diverticular disease group (P = ns). Of those with colonic
      fistulae, 16% were taking nicorandil compared with 2% of the control group (odds
      ratio 7.8; 95% confidence interval 1.5-39.1; P = 0.008). There was no significant
      difference in rates of ischaemic heart disease between fistula and control
      groups. CONCLUSIONS: Nicorandil is associated with fistula formation in
      diverticular disease.

PMID- 20819333
TI  - NHS Evidence--promoting efficiency and quality through evidence-based decisions.

PMID- 20819334
TI  - Whole gut intubation splinting--last refuge for the surgically desperate?

PMID- 20819335
TI  - Pharyngojejunal tubes for feeding after upper gastrointestinal surgery: the way
      forward.

PMID- 20819336
TI  - Simple technique for retraction of the gallbladder in laparoscopic
      cholecystectomy.

PMID- 20819337
TI  - Arthroscopic knee washout.

PMID- 20819338
TI  - A safe technique for olecranon osteotomy.

PMID- 20819339
TI  - An alternative technique for mesh repair of an incisional hernia.

PMID- 20819340
TI  - Seton sutures for leg ulcers associated with fistulous tracts.

PMID- 20819341
TI  - Quantitative banding for steal syndrome secondary to arteriovenous fistulae.

PMID- 20819342
TI  - Pancreatic cancer in the media: the Swayze shift.

PMID- 20819343
TI  - Bariatric surgery should be considered as a potential intervention for the obese
      patient with osteoarthritis.

PMID- 20819344
TI  - Operative tourniquets.

PMID- 20819345
TI  - The 'defensibility' of surgical injuries.

PMID- 20819346
TI  - Testing the distal tibiofibular syndesmosis--comment 2.

PMID- 20819347
TI  - Testing the distal tibiofibular syndesmosis--comment 1.

PMID- 20819348
TI  - Medicolegal claims and intra-operative cholangiography.

PMID- 20819349
TI  - Pulsed UV light inactivation of Salmonella enteritidis on eggshells and its
      effects on egg quality.
AB  - The majority of Salmonella Enteritidis outbreaks have been related to the
      consumption of raw or undercooked eggs or egg-containing foods. Therefore, the
      U.S. Department of Agriculture mandates egg washing for all graded eggs by use of
      a detergent solution and sanitizer. These agencies and the egg industry have been
      investigating alternative decontamination techniques, which could better serve
      the public, minimize costs, and benefit both the public and the industry. Pulsed
      UV light is an emerging technology that is used to inactivate microorganisms
      quickly. In this study, the effectiveness of pulsed UV light was evaluated for
      the decontamination of eggshells. Eggs inoculated with Salmonella Enteritidis on
      the top surface at the equator were treated with pulsed UV light 1 to 30 s, at a
      distance of 9.5 and 14.5 cm from the UV lamp in a laboratory-scale, pulsed UV
      light chamber. Three eggs were used per treatment in each repetition, except for
      quality measurements, which involved six eggs per treatment in each repetition. A
      maximum log reduction of 5.3 CFU/cm2 was obtained after a 20-s treatment at 9.5
      cm below the UV lamp at a total dose of 23.6+/-0.1 J/cm2, without any visual
      damage to the egg. After a 30-s treatment at 9.5 and 14.5 cm, the temperature of
      eggshell surfaces increased by 16.3 and 13.3 degrees C, respectively. Energy
      usage increased up to 35.3+/-0.1 and 24.8+/-0.1 J/cm2, after 30-s treatments at
      9.5 and 14.5 cm, respectively. The effect of pulsed UV light treatments on egg
      quality was also evaluated. Pulsed UV-light treatments for 3, 10, and 20s at
      either 9.5 or 14.5 cm did not change the albumen height, eggshell strength, or
      cuticle presence significantly (P<0.05). This study demonstrated that pulsed UV
      light has potential to decontaminate eggshell surfaces.

PMID- 20819350
TI  - Modeling prevalence and counts from most probable number in a bayesian framework:
      an application to Salmonella typhimurium in fresh pork sausages.
AB  - Prevalence and counts of Salmonella Typhimurium in fresh pork sausage packs at
      the point of retail were modeled by using Irish and United Kingdom retail
      surveys' data. A methodology for modeling a second-order distribution for the
      initial Salmonella concentration (lambda0) in pork sausage at retail was
      presented considering the uncertainty originated from the most probable-number
      (MPN) serial dilutions. A conditional probability of observing the tube counts
      given true Salmonella concentration in a contaminated pack was built from the MPN
      triplets of every sausage tested. A posterior distribution was then modeled under
      the assumption that the counts from each of the portions of sausage mix stuffed
      into casings (and subsequently packed) are Poisson distributed. In order to model
      the variability of lambda0 among contaminated sausage packs, MPN uncertainties
      were propagated to a predefined lognormal distribution. Because the sausage
      samples from the Irish survey were frozen prior to MPN analysis (which is
      expected to cause reduction in viable cells), the resulting distribution for
      lambda0 appeared greatly underestimated (mean: 0.514 CFU/g; 95% confidence
      interval [CI]: 0.02 to 2.74 CFU/g). The lambda0 distribution produced with the
      United Kingdom survey data (mean: 69.7 CFU/g; 95% CI: 15 to 200 CFU/g) was,
      however, more conservative, and is to be used along with the fitted distribution
      for prevalence of Salmonella Typhimurium in pork sausage packs in Ireland
      (gamma[37.997, 0.0013]; mean: 0.046; 95% CI: 0.032 to 0.064) as the main inputs
      of a stochastic consumer-phase exposure assessment model.

PMID- 20819351
TI  - Incidence and behavior of Salmonella and Escherichia coli on whole and sliced
      zucchini squash (Cucurbitapepo) fruit.
AB  - The incidence of coliform bacteria (CB), thermotolerant coliforms (TC),
      Escherichia coli, and Salmonella was determined for zucchini squash fruit. In
      addition, the behavior of four serotypes of Salmonella and a cocktail of three E.
      coli strains on whole and sliced zucchini squash at 25+/-2 degrees C and 3 to 5
      degrees C was tested. Squash fruit was collected in the markets of Pachuca city,
      Hidalgo State, Mexico. CB, TC, E. coli, and Salmonella were detected in 100, 70,
      62, and 10% of the produce, respectively. The concentration ranged from 3.8 to
      7.4 log CFU per sample for CB, and >3 to 1,100 most probable number per sample
      for TC and E. coli. On whole fruit stored at 25+/-2 degrees C or 3 to 5 degrees
      C, no growth was observed for any of the tested microorganisms or cocktails
      thereof. After 15 days at 25+/-2 degrees C, the tested Salmonella serotypes had
      decreased from an initial inoculum level of 7 log CFU to <1 log, and at 3 to 5
      degrees C they decreased to approximately 2 log. Survival of E. coli was
      significantly greater than for the Salmonella strains at the same times and
      temperatures; after 15 days, at 25+/-2 degrees C E. coli cocktail strains had
      decreased to 3.4 log CFU per fruit and at 3 to 5 degrees C they decreased to 3.6
      log CFU per fruit. Both the Salmonella serotypes and E. coli strains grew when
      inoculated onto sliced squash: after 24 h at 25+/-2 degrees C, both bacteria had
      grown to approximately 6.5 log CFU per slice. At 3 to 5 degrees C, the bacterial
      growth was inhibited. The squash may be an important factor contributing to the
      endemicity of Salmonella in Mexico.

PMID- 20819352
TI  - Prevalence, antibiograms, and transferable tet(O) plasmid of Campylobacter jejuni
      and Campylobacter coli isolated from raw chicken, pork, and human clinical cases
      in Korea.
AB  - The antibiotic resistance patterns and prevalence of the transferable tet(O)
      plasmid were investigated in Campylobacter jejuni and Campylobacter coli isolates
      from raw chicken, pork, and humans with clinical campylobacteriosis. A total of
      180 C. jejuni and C. coli isolates were identified, and the prevalence rates of
      C. jejuni and C. coli in raw chicken samples were 83% (83 of 100) and 73% (73 of
      100), respectively. Twelve percent (6 of 50) and 10% (5 of 50) of pork samples
      were contaminated with C. jejuni and C. coli, respectively. Disk diffusion
      susceptibility testing revealed that the most frequently detected resistance was
      to tetracycline (92.2%), followed by nalidixic acid (75.6%), ciprofloxacin
      (65.0%), azithromycin (41.5%), ampicillin (33.3%), and streptomycin (26.1%). Of
      the C. jejuni and C. coli isolates, 65.7% (n=109) contained plasmids carrying the
      tet(O) gene. Six C. jejuni isolates and two C. coli isolates with high-level
      resistance to tetracycline (MIC=256 microg/ml) harbored the tet(O) plasmid, which
      is transferable to other C. jejuni and C. coli isolates. These results
      demonstrate the presence of an interspecies transferable plasmid containing the
      tet(O) gene and a high prevalence of antibiotic resistance in Korean
      Campylobacter isolates and provide an understanding of the antibiotic resistance
      distribution among Campylobacter species in Korea.

PMID- 20819353
TI  - Survival of Campylobacter jejuni and Campylobacter coli on retail broiler meat
      stored at -20, 4, or 12 degrees C and development of Weibull models for survival.
AB  - Survival of Campylobacter jejuni and Campylobacter coli isolated from broiler
      meat was investigated and modeled on retail breast meat. Meat portions were
      inoculated with C. jejuni or C. coli at 6.4 to 6.8 log CFU/g followed by storage
      at -20 degrees C for 84 days or at 4 or 12 degrees C for 14 days. Kinetic data
      within a species and temperature were fitted to the Weibull model. When >or=70%
      of the residuals were in an acceptable prediction zone from -1 (fail-safe) to 0.5
      (fail-dangerous) log units, the model was considered to have acceptable
      performance. Survival of Campylobacter was highest at 4 degrees C, lowest at 12
      degrees C, and intermediate at -20 degrees C. Survival of C. jejuni and C. coli
      was similar at -20 degrees C but was lower (P<0.05) for C. jejuni than for C.
      coli at 4 and 12 degrees C. The Weibull model provided acceptable predictions for
      four of six sets of dependent data with unacceptable performance for survival of
      C. jejuni at -20 and 12 degrees C. A difference in survival was observed between
      the two strains of C. jejuni tested. Comparison of Weibull model predictions with
      data for C. jejuni archived in ComBase revealed mostly unacceptable performance,
      indicating that C. jejuni and C. coli survival on raw broiler breast meat differs
      from published results for other strains and growth media. Variation in
      Campylobacter survival among replicate storage trials was high, indicating that
      performance of the models can be improved by collection of additional data to
      better define the survival response during storage at temperatures from -20 to 12
      degrees C.

PMID- 20819354
TI  - Performance of food safety management systems in poultry meat preparation
      processing plants in relation to Campylobacter spp. contamination.
AB  - A diagnostic instrument comprising a combined assessment of core control and
      assurance activities and a microbial assessment instrument were used to measure
      the performance of current food safety management systems (FSMSs) of two poultry
      meat preparation companies. The high risk status of the company's contextual
      factors, i.e., starting from raw materials (poultry carcasses) with possible high
      numbers and prevalence of pathogens such as Campylobacter spp., requires advanced
      core control and assurance activities in the FSMS to guarantee food safety. The
      level of the core FSMS activities differed between the companies, and this
      difference was reflected in overall microbial quality (mesophilic aerobic count),
      presence of hygiene indicators (Enterobacteriaceae, Staphylococcus aureus, and
      Escherichia coli), and contamination with pathogens such as Salmonella, Listeria
      monocytogenes, and Campylobacter spp. The food safety output expressed as a
      microbial safety profile was related to the variability in the prevalence and
      contamination levels of Campylobacter spp. in poultry meat preparations found in
      a Belgian nationwide study. Although a poultry meat processing company could have
      an advanced FSMS in place and a good microbial profile (i.e., lower prevalence of
      pathogens, lower microbial numbers, and less variability in microbial
      contamination), these positive factors might not guarantee pathogen-free
      products. Contamination could be attributed to the inability to apply effective
      interventions to reduce or eliminate pathogens in the production chain of (raw)
      poultry meat preparations.

PMID- 20819355
TI  - Comparison of chromogenic Biolog Rainbow agar Shigella/Aeromonas with xylose
      lysine desoxycholate agar for isolation and detection of Shigella spp. from
      foods.
AB  - Shigella outbreaks are widely reported throughout the world. However, it remains
      a challenge to isolate Shigella spp. from foods by using conventional
      microbiological media. The main objective of this study was to determine the
      effectiveness of a novel chromogenic medium, Rainbow agar Shigella/Aeromonas
      (Rainbow agar), for the isolation and detection of Shigella spp. in foods. All
      four Shigella species, S. sonnei, S. flexneri, S. dysenteriae, and S. boydii,
      were studied. Rainbow agar was compared with tryptic soy agar, xylose lysine
      desoxycholate agar (XLD), and Salmonella Shigella agar (SSA) for enumeration of
      Shigella spp. in pure culture. This chromogenic agar and XLD were also used to
      isolate Shigella spp. in artificially contaminated foods (4.8 log CFU/g of food),
      including lettuce, parsley, cilantro, spinach, potato salad, and shrimp. The
      inhibitory effect on Shigella growth by Rainbow agar was between that of XLD and
      SSA. All vegetables studied showed a moderately high background microflora on XLD
      and Rainbow agar. With artificially inoculated produce, Rainbow agar recovered
      about 1 to 2 log CFU more S. sonnei, S. dysenteriae, and S. boydii per g of food
      than did XLD. For potato salad and shrimp, which had low background microflora on
      Rainbow agar, Rainbow agar was slightly better in recovering Shigella spp. than
      XLD was in most cases. However, we found that the addition of streptomycin (6.25
      mg/liter) to Rainbow agar could facilitate the isolation of Shigella in
      vegetables tested. In conclusion, Rainbow agar was a much more effective medium
      than was XLD for the isolation of Shigella spp. from foods.

PMID- 20819356
TI  - An ELISA-on-a-chip biosensor system coupled with immunomagnetic separation for
      the detection of Vibrio parahaemolyticus within a single working day.
AB  - In this study, we constructed a rapid detection system for a foodborne pathogen,
      Vibrio parahaemolyticus, by using enzyme-linked immunosorbent assay (ELISA)-on-a
      chip (EOC) biosensor technology to minimize the risk of infection by the
      microorganism. The EOC results showed a detection capability of approximately
      6.2x10(5) cells per ml, which was significantly higher than that of the
      conventional rapid test kit. However, this high level of sensitivity required
      cultivation of the pathogen prior to analysis, which typically exceeded a day. To
      shorten the test period, we combined the EOC technology with immunomagnetic
      separation (IMS), which could enhance the sensitivity of the biosensor. IMS was
      carried out with magnetic particles coated with a monoclonal antibody specific to
      the microbe. To test the performance of the IMS-EOC method, fish intestine
      samples were prepared by artificially inoculating less than 1 or 5 CFU/10 g,
      allowing for enrichment over predetermined times, and analyzing the sample by
      using the EOC sensor after concentrating the culture 86-fold via IMS. Using this
      approach, the bacterium was detected after (at most) 9 h, which approximately
      corresponds to standard working hours. Thus, the IMS-EOC method allowed for the
      rapid detection of V. parahaemolyticus, which is responsible for foodborne
      diseases, and this method could be used for early isolation of contaminated foods
      before distribution.

PMID- 20819357
TI  - Inactivation of a cold-induced putative rna helicase gene of Listeria
      monocytogenes is accompanied by failure to grow at low temperatures but does not
      affect freeze-thaw tolerance.
AB  - Freeze-thaw tolerance (cryotolerance) of Listeria monocytogenes is markedly
      influenced by temperature of growth of the bacteria, and may involve responses to
      low-temperature stresses encountered during freezing and thawing. A cold
      sensitive mariner-based transposon mutant of L. monocytogenes F2365 was found to
      harbor a single insertion in LMOf2365_1746, encoding a putative RNA helicase, and
      earlier shown by other investigators to be induced during 4 degrees C growth of
      L. monocytogenes. The mutant had normal growth at 37 degrees C but completely
      failed to grow at either 4 or 10 degrees C, and had impaired growth and reduced
      swarming on soft agar at 25 degrees C. However, the mutation had no discernible
      influence on the ability of the bacteria to tolerate repeated freezing and
      thawing after growth at either 25 or 37 degrees C. The findings suggest that the
      transposon insertion in the putative helicase gene, in spite of the severely cold
      sensitive phenotype that accompanies it, does not affect the ability of the
      bacteria to cope with cold-related stresses encountered during repeated freezing
      and thawing.

PMID- 20819358
TI  - Evaluation of a real-time PCR assay for the detection and quantification of
      Bacillus cereus group spores in food.
AB  - A procedure based on quantitative real-time PCR was evaluated for the detection
      and quantification of Bacillus cereus spores. Several methods for DNA isolation,
      such as various heat treatments and germination solutions, were evaluated on
      spore suspensions of representative strains of the B. cereus group. Overall, the
      commercially available DNeasy tissue kit yielded the maximum amount of DNA. The
      procedure also was used to construct calibration curves for different food
      matrices, with a wide spore quantification range of 5 log units using serial
      dilutions of spore suspensions of B. cereus CECT 148T. The detection limit for B.
      cereus in artificially contaminated liquid egg and reconstituted infant formula
      was about 4 spores per reaction or 60 spores per ml. The newly developed
      methodology based on the DNeasy tissue kit and an SYBR Green quantitative real
      time PCR assay is very suitable for the rapid and accurate detection and
      quantification of B. cereus group strains and their spores in food samples.

PMID- 20819359
TI  - A rapid method for identifying Byssochlamys and Hamigera.
AB  - Heat-resistant fungi, genera Byssochlamys, Talaromyces, Neosartorya, and
      Hamigera, contribute significantly to the spoilage of heat-processed acidic
      foods, due to the formation of heat-resistant ascospores. Here, we first
      evaluated the differences in the beta-tubulin gene between Byssochlamys and
      Hamigera and developed specific primers to identify the Byssochlamys species
      fulva, nivea, and spectabilis, and Hamigera. Using primers designed for B. fulva
      and B. nivea (B1F/1R), specific PCR products were detected for B. fulva and B.
      nivea, as well as B. langunculariae and B. zollerniae, two closely related
      species. Similarly, the Pae4F/4R-1 and H2F/2R primers produced specific PCR
      products for B. spectabilis and Hamigera, respectively. Using these three primer
      sets, strains involved in acidic food spoilage and environmental contamination
      were not detected. The detection limits of all primer sets were 1 ng of DNA by
      PCR and 10 pg of DNA by nested PCR. Each PCR assay was specific, even if the
      sample was contaminated 1,000-fold by other fungal DNA. Thus, this method has
      proved to possess an extremely high degree of specificity.

PMID- 20819361
TI  - Modeling the growth of Salmonella in cut red round tomatoes as a function of
      temperature.
AB  - Tomato-associated Salmonella outbreaks have recently become a significant food
      safety concern. Temperature abuse of cut tomatoes may have played a role in some
      of these outbreaks. The purpose of this study was to develop a mathematical model
      to describe the growth of Salmonella on cut tomatoes at various temperatures.
      Four Salmonella serotypes (Typhimurium, Newport, Javiana, and Braenderup)
      obtained from previous tomato-linked cases of salmonellosis were used in this
      study. These four serotypes were cultured separately, combined into a cocktail,
      and inoculated onto whole red round tomatoes and allowed to dry overnight. The
      tomatoes were then cut into pieces and incubated at a predetermined range of
      temperatures (10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, and 35 degrees C).
      Salmonella concentration was measured at specified time intervals to determine
      the growth curve for Salmonella on cut tomatoes at each temperature. The growth
      rates were calculated using DMFit and used to build a mathematical model to
      illustrate the relationship between the growth rates of Salmonella on tomatoes
      and incubation temperatures from 10 to 35 degrees C. The resulting model compared
      favorably with a Salmonella growth model for raw poultry developed by our
      laboratory. The Pathogen Modeling Program underpredicted growth at low
      temperatures and overpredicted growth at high temperatures. ComBase predicted
      consistently slower growth rates than were observed in tomatoes but showed
      parallel increases in growth rate with increasing temperature.

PMID- 20819360
TI  - Food-grade antioxidants and antimicrobials to control growth and ochratoxin a
      production by Aspergillus section Nigri on peanut kernels.
AB  - Each year, a significant portion of the peanuts produced cannot be marketed
      because of fungal disease at the postharvest stage and mycotoxin contamination.
      Antioxidants could be used as an alternative to fungicides to control
      ochratoxigenic fungi in peanuts during storage. This study was carried out to
      determine the effect of the antioxidant butylated hydroxyanisole (BHA) and the
      antimicrobial propyl paraben (PP) on the lag phase before growth, growth rate,
      and ochratoxin A (OTA) production by Aspergillus section Nigri strains in peanut
      kernels under different conditions of water activity (aw) and temperature. At 20
      mM/g BHA, 18 degrees C, and 0.93 aw, complete inhibition of growth occurred. For
      PP, there was no growth at 20 mM/g, 18 degrees C, and 0.93, 0.95, and 0.98 aw.
      BHA at 20 mM/g inhibited OTA production in peanuts by Aspergillus carbonarius and
      Aspergillus niger aggregate strains at 0.93 aw and 18 degrees C. PP at 20 mM/g
      completely inhibited OTA production at 18 degrees C. The results of this work
      suggest that PP is more appropriate than BHA for controlling growth and OTA
      production by Aspergillus section Nigri species in peanut kernels.

PMID- 20819362
TI  - Survival of Salmonella on a polypropylene surface under dry conditions in
      relation to biofilm-formation capability.
AB  - This study was conducted to gain insights into the survival of Salmonella on a
      polypropylene surface in relation to the ability of these bacteria to form a
      biofilm. We selected Salmonella strains known for the relative ease or difficulty
      with which they formed biofilms based on microtiter plate assays and studied the
      survival of these strains on polypropylene discs in a desiccation chamber by
      sequentially counting CFUs. The biofilm-forming strains survived longer on the
      plastic disc surface than did biofilm-deficient strains. The biofilm-forming
      strains remained at over 10(4) CFU per plate until day 175, whereas the biofilm
      deficient strains decreased to below 10(2) CFU per plate on day 20 or below 10(4)
      CFU per plate on day 108. Extracellular materials on the polypropylene surface
      were observed by scanning electron microscopy and crystal violet staining for the
      biofilm-forming strains but not for the biofilm-deficient strains. The
      extracellular polymeric materials on the polypropylene surface may have protected
      the bacterial cells from dryness, although the possibility of some inherent
      resistance to environmental stresses linked to biofilm formation could not be
      excluded. These results indicate that Salmonella strains with high biofilm
      productivity may be a greater risk to human health via food contamination by
      surviving for longer periods compared with strains with low biofilm productivity.

PMID- 20819363
TI  - Characterization of Listeria monocytogenes recovered from imported cheese
      contributed to the National PulseNet Database by the U.S. Food and Drug
      Administration from 2001 to 2008.
AB  - Imported foods must meet the same U.S. Food and Drug Administration (FDA)
      standards as domestic foods. The FDA determines whether an imported food is in
      compliance with the Federal Food, Drug, and Cosmetic Act. Pursuant to its
      regulatory activities, the FDA conducts compliance surveillance on imported foods
      offered for entry into the U.S. commerce. The National PulseNet Database is the
      molecular surveillance network for foodborne infections and is widely used to
      provide real-time subtyping support to epidemiologic investigations of foodborne
      diseases. FDA laboratories use pulsed-field gel electrophoresis to subtype
      foodborne pathogens recovered from imported foods and submit the molecular
      patterns to the National PulseNet Database at the Centers for Disease Control and
      Prevention. There were 60 isolates of Listeria monocytogenes in the FDA Field
      Accomplishment and Compliance Tracking System from 2001 to 2008 due to cheese
      imported from the following countries: Mexico (n=21 isolates), Italy (19), Israel
      (9), Portugal (5), Colombia (3), Greece (2), and Spain (1). We observed genetic
      diversity of L. monocytogenes isolates and genetic relatedness among strains
      recovered from imported cheese products coming to the United States from
      different countries. Consistent characterization of L. monocytogenes isolates
      recovered from imported cheeses, accompanied by epidemiologic investigations to
      ascertain human illness associated with these strains, could be helpful in the
      control of listeriosis acquired from imported cheeses.

PMID- 20819364
TI  - Prevalence of Listeria monocytogenes in ready-to-eat foods sampled from the point
      of sale in Wales, United Kingdom.
AB  - A survey of Listeria in ready-to-eat food took place in Wales, United Kingdom,
      between February 2008 and January 2009. In total, 5,840 samples were taken and
      examined for the presence of Listeria species, including L. monocytogenes.
      Samples were tested using detection and enumeration methods, and the results were
      compared with current United Kingdom guidelines for the microbiological quality
      of ready-to-eat foods. The majority of samples were negative for Listeria by both
      direct plating and enriched culture. Seventeen samples (0.29%) had countable
      levels of Listeria species (other than L. monocytogenes), and another 11 samples
      (0.19%) had countable levels of L. monocytogenes. Nine samples (0.15%) were
      unsatisfactory or potentially hazardous when compared with United Kingdom
      guideline limits; six (0.10%) were in the unsatisfactory category (>100 CFU/g)
      for Listeria species (other than L. monocytogenes), and three (0.05%) were in the
      unacceptable or potentially hazardous category (>100 CFU/g) for L. monocytogenes.
      All three of these samples were from sandwiches (two chicken sandwiches and one
      ham-and-cheese sandwich). The most commonly isolated serotype of L. monocytogenes
      was 1/2a. This survey was used to determine the current prevalence of Listeria
      species and L. monocytogenes in ready-to-eat foods sampled from the point of sale
      in Wales.

PMID- 20819365
TI  - Removal of Listeria monocytogenes biofilms with bacteriophage P100.
AB  - Listeria monocytogenes is an important foodborne pathogen with a persistent
      ability to form biofilm matrices in the food processing environments. In this
      study, we have determined the ability of bacteriophage P100 to reduce L.
      monocytogenes cell populations under biofilm conditions by using 21 L.
      monocytogenes strains representing 13 different serotypes. There were
      considerable differences in the ability of various strains of L. monocytogenes to
      form biofilms, with strains of serotype 1/2a showing maximum biofilm formation.
      Irrespective of the serotype, growth conditions, or biofilm levels, the phage
      P100 treatment significantly reduced L. monocytogenes cell populations under
      biofilm conditions. On the stainless steel coupon surface, there was a 3.5- to
      5.4-log/cm2 reduction in L. monocytogenes cells by phage treatment. These
      findings illustrate that phage P100 is active against a wide range of L.
      monocytogenes strains in biofilm conditions.

PMID- 20819366
TI  - Reclassification of the Listeria-CAMP test strain ATCC 49444 Staphylococcus
      aureus as Staphylococcus pseudintermedius.
AB  - ATCC 49444, originally designated as Staphylococcus aureus, has been cited as a
      component strain in the CAMP test for identification of Listeria monocytogenes. A
      polyphasic study, in which molecular data were combined with cytochemical
      properties and physiological characteristics, identified this isolate as
      Staphylococcus pseudintermedius. The nucleotide sequences of the 16S rRNA and
      sodA genes from ATCC 49444 were determined and found to be identical to those of
      other S. pseudintermedius strains. Ribotyping analysis of ATCC 49444 indicated a
      low (0.2) similarity index with S. aureus and Staphylococcus intermedius strains
      but a similarity index of more than 0.66 with S. pseudintermedius isolates. A
      functional comparison of ATCC 49444 with S. aureus ATCC 25923 utilizing the CAMP
      test demonstrated equivalent hemolytic enhancement with L. monocytogenes
      isolates. While this study demonstrates that ATCC 49444 is a valid component
      strain for the CAMP test, it is proposed that ATCC 49444 be reclassified as S.
      pseudintermedius and that users worldwide be alerted to this reclassification and
      name change.

PMID- 20819367
TI  - Evaluation of the petrifilm aerobic count plate for enumeration of aerobic marine
      bacteria from seawater and Caulerpa lentillifera.
AB  - The enumeration and evaluation of the activity of marine bacteria are important
      in the food industry. However, detection of marine bacteria in seawater or
      seafood has not been easy. The Petrifilm aerobic count plate (ACP) is a ready-to
      use alternative to the traditional enumeration media used for bacteria associated
      with food. The purpose of this study was to evaluate the usefulness of a simple
      detection and enumeration method utilizing the Petrifilm ACP for enumeration of
      aerobic marine bacteria from seawater and an edible seaweed, Caulerpa
      lentillifera. The efficiency of enumeration of total aerobic marine bacteria on
      Petrifilm ACP was compared with that using the spread plate method on marine agar
      with 80 seawater and 64 C. lentillifera samples. With sterile seawater as the
      diluent, a close correlation was observed between the method utilizing Petrifilm
      ACP and that utilizing the conventional marine agar (r=0.98 for seawater and 0.91
      for C. lentillifera). The Petrifilm ACP method was simpler and less time
      consuming than the conventional method. These results indicate that Petrifilm ACP
      is a suitable alternative to conventional marine agar for enumeration of marine
      microorganisms in seawater and C. lentillifera samples.

PMID- 20819368
TI  - Microbiological quality of wheat grain and flour from two mills in Queensland,
      Australia.
AB  - A baseline investigation of the microbiological quality of wheat grain and flour
      from two mills in Queensland, Australia, was undertaken in order to assess the
      capacity of these two mills to meet microbiological criteria specified by a
      customer for raw, non-heat-treated flour. This baseline testing was performed
      over the 2006 to 2007 wheat season. Three hundred fifty flour samples were
      monitored for yeast, mold, and Bacillus cereus, 300 for Escherichia coli, 150 for
      Salmonella, and 100 for aerobic plate count. Fifty grain samples were analyzed
      for yeast, mold, E. coli, Salmonella, and B. cereus. There was a single isolation
      of Salmonella Give in unscreened wheat. The yeast, mold, E. coli, and B. cereus
      prevalences were 56, 40, 2.0, and 4.0% for grain and 71, 17, 0.7, and <0.3% for
      flour, respectively. Of the positive samples, the means were 3.7, 2.7, 0.6, and
      2.1 for grain, and 3.0, 2.8, and 0.8 log CFU/g for flour. The mean of the aerobic
      plate count was 4.2 log CFU/g with a 95th percentile count of 4.6 log CFU/g. A
      microbiological quality baseline of wheat grain and flour from these two
      Queensland mills has been determined. These data in a specific sense assist the
      two mills to assess their capacity to meet microbiological criteria, and in a
      general sense provide at least a limited snapshot of Queensland wheat and flour
      quality for risk assessments being carried out to evaluate the safety of plant
      and plant products.

PMID- 20819369
TI  - Inactivation effects of UV irradiation and ozone treatment on the yeast and the
      mold in mineral water.
AB  - In recent years, bottled mineral water has undergone inactivation by methods
      other than the traditional heat treatment during the production process; there
      are fewer reports of the effectiveness of these inactivation methods on yeasts
      and molds in mineral water than on bacteria and protozoan oocysts. In this study,
      we evaluated the effects of UV irradiation and ozone treatment compared with heat
      treatment at 85 degrees C on yeast cells and mold spores inoculated into mineral
      water. A 5-log reduction occurred at a UV radiation dose of 31,433 microJ/cm2 for
      Saccharomyces cerevisiae and at 588,285 microJ/cm2 for Penicillium pinophilum.
      The treatment time for 5-log reduction estimated for UV irradiation was about 0.6
      min for S. cerevisiae and about 10.7 min for P. pinophilum; at an ozone
      concentration of 0.1 ppm, it was 1.75 min for S. cerevisiae and 2.70 min for P.
      pinophilum, and at a concentration of 0.6 ppm, it was 0.32 min for S. cerevisiae
      and 0.57 min for P. pinophilum. Comparison of the inactivation effects among the
      three methods showed that UV irradiation and ozone treatment were less effective
      than heat treatment at 85 degrees C. Thus, when UV irradiation and ozone
      treatment are used for inactivation of mineral water, it seems that they need to
      be combined with heat treatment to achieve a definite effect. Yeast cells are
      more sensitive to all three inactivation methods than are mold spores, and the
      sensitivity of yeast cells and mold spores to these inactivation methods may vary
      among genera.

PMID- 20819370
TI  - Fate of human enteric viruses during dairy manure-based composting.
AB  - Murine norovirus 1 (MNV-1), Aichi virus (AiV), and human adenovirus 41 (Ad41)
      were seeded in dairy manure and composted for 60 days, and both the stability of
      virus genomes and infectious viruses were evaluated. For compost started in late
      fall, pile temperature reached approximately 54.5 degrees C on day 1 and remained
      between 55 and 60 degrees C for 3 days. For viral genomes, AiV had an approximate
      1.4-log loss of viral genome after 1 day and more than a 3.1-log loss after 2
      days; while for MNV-1, there was a roughly 0.6-log reduction on day 1 and a more
      than 4-log reduction after 5 days. For compost started in late spring, the center
      temperature reached about 70 degrees C on day 1 and remained warmer than 65
      degrees C for 3 days. The MNV-1 viral genome level was below the detection limit
      (ca. 3.4 log reverse transcriptase and quantitative PCR unit per g) after 1 day.
      Compared with RNA viruses, the Ad41 DNA genome was more stable in compost started
      in late spring; there was no reduction in DNA after 1 day, and ca. a 2.1-log loss
      at 5 and 7 days. For viral infectivity, the AiV infectious concentration was
      below the detection limit (about 2.8 log tissue culture infectious dose assay per
      g) after day 1 for both trials 1 and 2, and for Ad41, there was a greater than 4
      log reduction of infectivity after 1 day for trial 2. Overall, temperature is a
      critical factor, which affects the survival of viruses in compost, and the fate
      of the viral genome in the generated heat is virus dependent as well. For U.S.
      Environmental Protection Agency Class A compost, current compost regulations
      require maintaining temperatures between 55 and 70 degrees C for at least for 3
      days for a static aerated-pile system. This study indicated that these
      temperature conditions could effectively inactivate MNV-1, AiV, and Ad41.

PMID- 20819371
TI  - Sources of low concentrations of bisphenol A in canned beverage products.
AB  - Although migration from can coatings is likely the source of bisphenol A (BPA)
      for the canned soft drink products with relatively high BPA concentrations,
      questions have been raised concerning the exact sources of BPA for those canned
      soft drink products with low BPA concentrations. Information is also needed for
      BPA concentrations in canned beer products to conduct proper exposure assessment
      for BPA under the Government of Canada's Chemicals Management Plan. In this work,
      22 soft drink samples and 16 beer samples in both cans and plastic and/or glass
      bottles were analyzed for BPA. BPA was not detected in any of the soft drink
      samples in either plastic or glass bottles except for one product with a BPA
      concentration (0.018 microg/liter) close to the limit of quantification (0.015
      microg/liter). BPA was detected in all of the corresponding soft drink products
      in cans, indicating that migration from can coatings is the likely source for BPA
      in canned products. Because considerable interference with ions m/z 213 and m/z
      228 from sample matrices was observed for all beer samples, BPA concentrations in
      beer samples were measured using the ion m/z 270 instead. BPA was detected in
      only one of the seven beer products in glass bottles (0.054 microg/liter) but was
      detected in all corresponding beer samples in cans at low concentrations ranging
      from 0.081 to 0.54 microg/liter, indicating that migration from can coatings is
      likely the source of BPA in canned beer products.

PMID- 20819372
TI  - Outbreaks where food workers have been implicated in the spread of foodborne
      disease. Part 7. Barriers to reduce contamination of food by workers.
AB  - Contamination of food and individuals by food workers has been identified as an
      important contributing factor during foodborne illness investigations. Physical
      and chemical barriers to prevent microbial contamination of food are hurdles that
      block or reduce the transfer of pathogens to the food surface from the hands of a
      food worker, from other foods, or from the environment. In food service
      operations, direct contact of food by hands should be prevented by the use of
      barriers, especially when gloves are not worn. Although these barriers have been
      used for decades in food processing and food service operations, their
      effectiveness is sometimes questioned or their use may be ignored. Physical
      barriers include properly engineered building walls and doors to minimize the
      flow of outside particles and pests to food storage and food preparation areas;
      food shields to prevent aerosol contamination of displayed food by customers and
      workers; work clothing designated strictly for work (clothing worn outdoors can
      carry undesirable microorganisms, including pathogens from infected family
      members, into the work environment); and utensils such as spoons, tongs, and deli
      papers to prevent direct contact between hands and the food being prepared or
      served. Money and ready-to-eat foods should be handled as two separate
      operations, preferably by two workers. Chemical barriers include sanitizing
      solutions used to remove microorganisms (including pathogens) from objects or
      materials used during food production and preparation and to launder uniforms,
      work clothes, and soiled linens. However, laundering as normally practiced may
      not effectively eliminate viral pathogens.

PMID- 20819373
TI  - Scientific and technical factors affecting the setting of Salmonella criteria for
      raw poultry: a global perspective.
AB  - Concerns about foodborne salmonellosis have led many countries to introduce
      microbiological criteria for certain food products. If such criteria are not well
      grounded in science, they could be an unjustified obstacle to trade. Raw poultry
      products are an important part of the global food market. Import and export
      ambiguities and regulatory confusion resulting from different Salmonella
      requirements were the impetus for convening an international group of scientific
      experts from 16 countries to discuss the scientific and technical issues that
      affect the setting of a microbiological criterion for Salmonella contamination of
      raw chicken. A particular concern for the group was the use of criteria implying
      a zero tolerance for Salmonella and suggesting complete absence of the pathogen.
      The notion can be interpreted differently by various stakeholders and was
      considered inappropriate because there is neither an effective means of
      eliminating Salmonella from raw poultry nor any practical method for verifying
      its absence. Therefore, it may be more useful at present to set food safety
      metrics that involve reductions in hazard levels. Such terms as "zero tolerance"
      or "absence of a microbe" in relation to raw poultry should be avoided unless
      defined and explained by international agreement. Risk assessment provides a more
      meaningful approach than a zero tolerance philosophy, and new metrics, such as
      performance objectives that are linked to human health outcomes, should be
      utilized throughout the food chain to help define risk and identify ways to
      reduce adverse effects on public health.

PMID- 20819374
TI  - Considerations for the use of anesthetics in neurotoxicity studies.
AB  - Anesthetics are widely used in experiments investigating neurotoxicity and
      neuroprotection; however, these agents are known to interfere with the outcome of
      these experiments. The purpose of this overview is to review these effects and
      suggest methods for minimizing unintended consequences on experimental outcomes.
      Information on the neuroprotective and neurotoxic effects of isoflurane,
      dexmedetomidine, propofol, ketamine, barbiturates, halothane, xenon, carbon
      dioxide, and nitrous oxide is summarized. The pertinent cell signaling pathways
      of these agents are discussed. Methods of humane animal euthanasia without
      anesthetics are considered. Most anesthetics alter the processes of neuronal
      survival and death. When designing survival surgeries, sham controls subjected to
      anesthesia but not the surgical intervention should be compared with controls
      subjected to neither anesthesia nor surgery. Additional controls could include
      using an anesthetic with a different mechanism of action from the primary
      anesthetic used. Because the effects of anesthetics lessen with time after
      surgery, survival surgeries should include later time points until at least 7 d
      after the procedure. Humane methods of animal euthanasia that do not require
      anesthetics exist and should be used whenever appropriate.

PMID- 20819375
TI  - Quantitation of acute phase proteins and protein electrophoresis in monitoring
      the acute inflammatory process in experimentally and naturally infected mice.
AB  - Serologic screening for infectious disease in sentinel mice from rodent colonies
      is expensive and labor-intensive, often involving multiple assays for several
      different infectious agents. Previously, we established normal reference ranges
      for the protein fractions of several laboratory strains of mice by using a
      commercially available agarose system of protein electrophoresis. In the current
      study, we address protein fractionation and quantitation of acute phase proteins
      (APP) in mice experimentally infected with Sendai virus or mouse parvovirus. We
      further investigate this methodology by using samples from sentinel mice from
      colonies with endemic infection. All study groups showed significant increases in
      gamma globulins. Various other protein fractions showed mild variable changes;
      significant differences were not detected for individual APP. These results
      contrast the significant changes observed in APP and protein electrophoresis by
      using the standard methods of inducing inflammatory responses through injection
      of complete Freund adjuvant or LPS. These present data suggest that although
      quantitation of individual APP may not be helpful, gamma globulin levels may
      reflect infection in laboratory mice and provide a possible adjunct to
      traditional screening methods.

PMID- 20819377
TI  - Insulin-induced hypoglycemic peripheral motor neuropathy in spontaneously
      diabetic WBN/Kob rats.
AB  - Intensive insulin therapy can lead to hypoglycemia, with patients sometimes
      developing hypoglycemic neuropathy. Spontaneously diabetic Wistar Bonn Kobori
      (WBN/Kob) rats develop diabetic peripheral motor neuropathy characterized by
      segmental demyelination and axonal degeneration. We examined the short-term
      effects of hypoglycemia on neuropathic changes in these rats. Spontaneous
      diabetic WBN/Kob rats received insulin implants for 40 d and were divided into 3
      groups based on blood glucose levels: group N, normoglycemic to slightly
      hyperglycemic (150 to 250 mg/dL); group H, hypoglycemic to slightly hyperglycemic
      (50 to 200 mg/dL); and group D, nontreated spontaneously diabetic (350 to 420
      mg/dL). Conduction velocity was measured in sciatic-tibial motor nerves; these
      nerves also underwent qualitative and quantitative histomorphologic analysis.
      Conduction velocity was not significantly different in N, D, and H groups.
      Morphologic analysis of the sciatic nerves of H rats showed severe changes,
      including axonal degeneration, myelin distention, and endoneurial fibrosis, that
      tended to occur in large, myelinated fibers. N and D rats showed relatively mild
      changes. The degree and distribution of degenerated nerve fibers in H rats were
      significantly higher than in N and D rats. These results suggest that
      hypoglycemia of less than 50 mg/dL induced severe peripheral neuropathy.
      Hypoglycemic lesions differed from the hyperglycemic lesions in diabetic WBN/Kob
      rats. This rat strain is an appropriate model for investigating the hypoglycemic
      peripheral neuropathy that can be associated with a diabetic condition.

PMID- 20819376
TI  - Lack of association of a spontaneous mutation of the Chrm2 gene with behavioral
      and physiologic phenotypic differences in inbred mice.
AB  - The nucleotide substitution C797T in the Chrm2 gene causes substitution of
      leucine for proline at position 266 (P266L) of the CHRM2 protein. Because Chrm2
      codes for the type 2 muscarinic receptor, this mutation could influence
      physiologic and behavioral phenotypes of mice. Chrm2 mRNA was not differentially
      expressed in 2 brain regions with high cholinergic innervation in a mouse strain
      that does (BALB/cByJ) or does not (C57BL/6J) have the mutation. In addition,
      strains of mice with and without the C797T point mutation in Chrm2 did not differ
      significantly in muscarinic binding properties. Variation across strains was
      detected in terms of acoustic startle, prepulse inhibition, and the physiologic
      effects of the muscarinic agonist oxotremorine. However, interstrain differences
      in these measures did not correlate with the presence of the mutation. Although
      we were unable to associate a measurable phenotype with the Chrm2 mutation,
      assessment of the mutation on other genetic backgrounds or in the context of
      other traits might reveal differential effects. Therefore, despite our negative
      findings, evaluation of characteristics that involve muscarinic function should
      be undertaken with caution when comparing mice with different alleles of the
      Chrm2 gene.

PMID- 20819378
TI  - Spatiotemporal expression of tmie in the inner ear of rats during postnatal
      development.
AB  - The circling (cir/cir) mouse is a murine model for human nonsyndromic deafness
      DFNB6. Transmembrane inner ear (tmie) is the causative gene and its mutation
      through deletion of a 40-kilobase genomic region including tmie leads to
      deafness. The function of Tmie is unknown. To better understand the function of
      Tmie, we focused on the spatiotemporal expression of tmie in the rat cochlea by
      using a Tmie-specific antibody. Results showed that tmie expression was prominent
      in early postnatal rat cochleas in the stereocilia bundles of hair cells. The
      Tmie signal spread from the stereocilia to the hair cell body region and on to
      organ of Corti cells. No Tmie signal was observed in cell nuclei; Tmie was
      localized to the cytoplasm. Because Tmie is predicted to have 1 or 2
      transmembrane domains, we postulate that it is localized to membrane-based
      organelles or the plasma membrane. Our results imply that Tmie exists in the
      cytoplasm and may have a key role in the maturation and structure of stereocilia
      bundles in developing hair cells. After hair cell maturation, Tmie is thought to
      be involved in the maintenance of organ of Corti cells.

PMID- 20819379
TI  - Blood supply to the chicken femoral head.
AB  - The purpose of this study was to conduct a comprehensive evaluation of the
      vascular supply to the femoral head, including the vessels that give rise to the
      terminal perfusing branches. Using a casting agent, we highlighted the anatomy of
      the external iliac and ischiatic arteries with their associated branches after
      anatomic dissection of 24 hips from 12 Leghorn chickens. We confirmed published
      findings regarding perfusion of the femoral head and identified 3 previously
      undescribed arterial branches to this structure. The first branch (the acetabular
      branch of the femoralis artery) was supplied by the femoralis artery and directly
      perfused the acetabulum and femoral head. The second branch (the lateral
      retinacular artery) was a tributary of the femoralis artery that directly
      supplied the femoral head. Finally, we found that the middle femoral nutrient
      artery supplies a previously undescribed ascending intraosseous branch (the
      ascending branch of the middle femoral nutrient artery) that perfuses the femoral
      head. Precise understanding of the major vascular branches to the femoral head
      would allow for complete or selective ligation of its blood supply and enable the
      creation of a reproducible bipedal model of femoral head osteonecrosis.

PMID- 20819382
TI  - Clinical biochemistry parameters in C57BL/6J mice after blood collection from the
      submandibular vein and retroorbital plexus.

PMID- 20819380
TI  - Metabolic syndrome and coronary artery disease in Ossabaw compared with Yucatan
      swine.
AB  - Metabolic syndrome (MetS), a compilation of associated risk factors, increases
      the risk of type 2 diabetes and coronary artery disease (CAD, atherosclerosis),
      which can progress to the point of artery occlusion. Stents are the primary
      interventional treatment for occlusive CAD, and patients with MetS and
      hyperinsulinemia have increased restenosis. Because of its thrifty genotype, the
      Ossabaw pig is a model of MetS. We tested the hypothesis that, when fed high-fat
      diet, Ossabaw swine develop more features of MetS, greater native CAD, and
      greater stent-induced CAD than do Yucatan swine. Animals of each breed were
      divided randomly into 2 groups and fed 2 different calorie-matched diets for 40
      wk: control diet (C) and high-fat, high-cholesterol atherogenic diet (H). A bare
      metal stent was placed in the circumflex artery, and pigs were allowed to recover
      for 3 wk. Characteristics of MetS, macrovascular and microvascular CAD, in-stent
      stenosis, and Ca(2+) signaling in coronary smooth muscle cells were evaluated.
      MetS characteristics including, obesity, glucose intolerance, hyperinsulinemia,
      and elevated arterial pressure were elevated in Ossabaw swine compared to Yucatan
      swine. Ossabaw swine with MetS had more extensive and diffuse native CAD and in
      stent stenosis and impaired coronary blood flow regulation compared with Yucatan.
      In-stent atherosclerotic lesions in Ossabaw coronary arteries were less fibrous
      and more cellular. Coronary smooth muscle cells from Ossabaw had impaired Ca(2+)
      efflux and intracellular sequestration versus cells from Yucatan swine.
      Therefore, Ossabaw swine are a superior model of MetS, subsequent CAD, and
      cellular Ca(2+) signaling defects, whereas Yucatan swine are leaner and
      relatively resistant to MetS and CAD.

PMID- 20819383
TI  - Normal organ weights, serum chemistry, hematology, and cecal and nasopharyngeal
      bacterial cultures in the gray short-tailed opossum (Monodelphis domestica).
AB  - Gray short-tailed opossums (Monodelphis domestica) currently are used in genetic,
      developmental, oncology, and neurologic research. Little is known about their
      natural flora or potential for pathogenic infectious disease. The present study
      aims to improve existing comparative normal blood and organ weight values
      available to researchers and to describe flora of clinically normal M. domestica
      to obtain an understanding of potential pathogenic flora in clinically abnormal
      animals. For evaluation of serum hematology and serum chemistry, clinically
      normal animals were assigned to 1 of 6 groups stratified by age (younger than 1
      y, 1 to 2 y, and 2 to 3 y) and sex. Hemoglobin and phosphorus levels were higher
      in male than female opossums, whereas monocyte and eosinophil counts were greater
      in females than males. Hemoglobin concentration decreased with increasing age.
      The youngest group had significantly higher levels of serum alkaline phosphatase
      and lower serum protein levels compared with older age groups. Liver and kidney
      weights of adult animals (1 to 3 y) were greater in female than male opossums.
      The predominant nasopharyngeal flora in 20 clinically normal animals from the 2-
      to 3-y-old group were Streptococcus viridans, Escherichia coli, and coagulase
      negative Staphylococcus spp.; predominant cecal organisms were Escherichia coli
      and Citrobacter spp. The availability of reference hematologic values and flora
      for Monodelphis domestica will aid researchers in comparisons and analysis of
      experimental data and in diagnosis and evaluation of potential pathogens in
      clinically ill animals.

PMID- 20819384
TI  - Survey of prevalence of overweight body condition in laboratory-housed cynomolgus
      macaques (Macaca fascicularis).
AB  - Excessive weight gain has been reported to occur in captive cynomolgus macaques
      with little to no change in diet. Overweight body condition can result in
      development of hyperglycemia and type 2 diabetes and should be avoided. The
      purpose of this survey was to assess the prevalence of overweight cynomolgus
      macaques in North American research facilities, including breeding colonies and
      short-term and long-term facilities, and to describe current methods used to
      assess body condition. The survey consisted of 51 questions covering animal
      population demographics, body weight and body condition scoring, feeding, and
      behavior. Voluntary participants included veterinarians and animal care managers.
      Respondents from 13 facilities completed the survey, and information was
      collected on 17,500 cynomolgus macaques. The majority of surveyed facilities
      housed juvenile and young adult macaques. The reported prevalence of overweight
      (greater than 10% of ideal body weight) animals ranged between 0% and 20% and
      reportedly was more frequent in animals younger than 10 y. Most facilities had
      weight reduction strategies in place. Despite these programs, a significant
      proportion of animals were reported as being overweight. The results of this
      survey demonstrate that most North American facilities housing cynomolgus
      macaques recognize the importance of tracking body condition regularly. However,
      implementing effective weight reduction programs may be difficult in captive
      housing environments. Because of the potential for adverse health effects,
      facilities should have a means of regularly tracking body weight as well as an
      action plan for managing overweight animals.

PMID- 20819385
TI  - Short-term storage and transport at cold temperatures of 2-cell mouse embryos
      produced by cryopreserved sperm.
AB  - At refrigerated temperatures, mouse embryos can maintain developmental ability
      for short periods. Previously, we succeeded in transporting vitrified and warmed
      2-cell mouse embryos while maintaining developmental ability at refrigerated
      temperatures for 50 h. Transport of nonfrozen embryos is an easier and more
      useful means of exchanging genetically engineered mice between laboratories than
      is transport of cryopreserved embryos. Here we examined the developmental ability
      of transported 2-cell embryos that were produced through in vitro fertilization
      using cryopreserved sperm. Results show that 2-cell embryos produced by
      cryopreserved sperm can develop into blastocysts after cold storage for 24, 48,
      and 72 h. Transported 2-cell embryos produced by cryopreserved sperm yielded a
      favorable number of pups in all of the receiving laboratories after transport
      lasting 48 to 52 h. In summary, cold storage and transport of 2-cell embryos
      derived from cryopreserved sperm at refrigerated temperatures provides a novel
      means of transporting genetically engineered mice as an alternative to the
      transport of cryopreserved embryos and sperm.

PMID- 20819386
TI  - Refinements in the cryopreservation of mouse ovaries.
AB  - Here we describe a new technique for cryopreserving mouse ovaries by using 0.5-mL
      straws. One advantage of this method is that it uses the same controlled-rate
      freezer and programming routinely used for the cryopreservation of mouse embryos.
      Using a 0.5-mL French straw loaded in the same way as for embryo freezing (for
      example, the one-step dilution method) with 1 M sucrose as an osmotic buffer and
      2 M propylene glycol as the cryoprotectant containing the ovary sample, we
      further standardized the 2 methodologies. Applying this technique, 11 ovarian
      halves were cryopreserved in straws and stored under liquid nitrogen. Straws
      containing the frozen ovarian halves were thawed in a water bath at room
      temperature and the recovered ovaries orthotopically implanted into 11 recipient
      female mice; 8 of the 11 frozen ovarian halves resulted in functional ovaries.
      The 73% pregnancy rate resulted in a total of 53 pups born, of which 38 (72%)
      were generated from cryopreserved ovaries. Ovarian cryopreservation has been
      demonstrated to be a valid option for banking mouse genetic resources. Unlike
      frozen embryos, cryopreservation of ovarian tissue preserves haploid gametes.
      Despite this limitation, ovarian cryopreservation is the only technique that can
      be used to preserve oocytes from aged or problematic breeders. This advantage is
      especially important in situations where the only males available in the line are
      infertile, aged, or problematic breeders.

PMID- 20819387
TI  - The effects of perioperative analgesia on litter size in Crl:CD1(ICR) mice
      undergoing embryo transfer.
AB  - The objective of this study was to evaluate the effect on litter size of 2
      analgesics used perioperatively during mouse embryo transfer surgery. Day 2.5
      pseudopregnant CD1 mice (n = 96) were divided equally into 2 analgesic treatment
      groups and a saline control group. Each mouse received a single, subcutaneous
      dose of buprenorphine hydrochloride (0.1 mg/kg), flunixin meglumine (2.5 mg/kg),
      or saline immediately after induction of anesthesia with 2.5% isoflurane. Each
      mouse then was prepared for aseptic surgery. Blastocysts had previously been
      collected from C57BL/6NCrl female mice that were synchronized and superovulated
      by using pregnant mare serum gonadotropin and human chorionic gonadotropin and
      mated with C57BL/6NTac male mice 3.5 d before collection. Viable blastocysts were
      pooled, and 8 were selected arbitrarily and transplanted into the right uterine
      horn of each pseudopregnant CD1 mouse. Mice were monitored throughout pregnancy,
      and the number of pups at birth was documented. No statistically significant
      difference was found between the 3 groups. These results indicate that
      perioperative analgesic treatment with buprenorphine or flunixin in the CD1 mouse
      undergoing embryo transfer is not associated with increased embryonic loss.

PMID- 20819388
TI  - Environmental-enrichment-related variations in behavioral, biochemical, and
      physiologic responses of Sprague-Dawley and Long Evans rats.
AB  - The behavioral, biochemical, and physiologic consequences of 6 wk of
      environmental enrichment were evaluated in male Long Evans and Sprague-Dawley
      rats and compared with those of rats in standard single-housing conditions.
      Standard housing provided little or no social or physical stimulation whereas
      environmental enrichment comprised group housing for 8 h daily in a 3-story cage
      equipped with novel stimuli. Dependent measures included performance in the
      forced swim test, thresholds for brain-stimulation reward, sucrose intake and
      preference, determination of corticosterone levels before and after brief
      restraint stress, and rate of weight gain. In forced swimming tests, active
      behaviors (diving, swimming with struggling, and climbing) tended to dominate
      over passive behaviors (sinking, floating) in both groups and outbred rat stocks
      (especially in enriched groups) on the first day. These behaviors were replaced
      with maintenance behaviors such as grooming and swimming without struggling on
      the second exposure, with enriched Long Evans rats showing the largest decline in
      activity. Baseline plasma corticosterone levels were elevated in both rat stocks
      after 6 wk of enrichment. After restraint stress, hormone levels in enriched
      animals tended to peak earlier and approach or exceed baseline values more
      quickly than was observed in the comparable control groups. Rate of body weight
      gain was greater in enriched Long Evans rats than Sprague-Dawley or control rats.
      Our observations indicate that stock- and group-associated differences in several
      indices occur in association with enrichment. The data support the claim that
      environmental enrichment may render animals more resilient to challenges.

PMID- 20819389
TI  - Serologic prevalence of MPV1 in mouse strains in a commercial laboratory mouse
      colony determined by using VP1 antigen.
AB  - A mouse parvovirus (designated MPV1f) was identified in a commercial laboratory
      mouse colony in Australia. The infection had not been detected by using an rNS1
      parvovirus ELISA antigen even though the virus was genetically similar to other
      MPV1 variants reported previously. A recombinant biotinylated protein based on a
      truncated VP1 protein of the MPV1 strain was produced and used as antigen for
      ELISA and Western immunoblots to detect virus infection and determine the
      seroprevalence of infection in a colony of approximately 45,000 mice. Antibody
      positive mice were detected in 8 of 11 rooms sampled, indicating that infection
      was widespread in the facility. Antibody was detected in 16.2% of 1161 sera
      obtained from 20 strains of mice. Seroprevalence varied among mouse strains,
      suggesting genetic variation in the susceptibility of mice to MPV1 or in their
      antibody response to infection, as has been reported previously in experimentally
      infected mice. Seroprevalence was high in some inbred strains, including
      DBA/2JArc and the random-bred strains Hsd:NIH and Arc:Arc(s). Antibody was not
      detected inC57BL/6J strains, and BALB/c strains showed low seroprevalence of
      MPV1f.

PMID- 20819390
TI  - Strain- and age-associated variation in viral persistence and antibody response
      to mouse parvovirus 1 in experimentally infected mice.
AB  - The effect of mouse strain and age at infection on viral replication and
      concurrent antibody response to mouse parvovirus 1 (isolate MPV1f) was evaluated
      for 305 d after inoculation in 4 strains of mice. The results confirmed previous
      reports that mouse strain and age at infection are significant factors in viral
      persistence and antibody development and detection. Randombred Arc:Arc(s) mice
      originally bred from CD1 stock inoculated as juveniles (4 wk) or adults (8 wk)
      developed persistent viral infection for 152 d after inoculation and an antibody
      response that persisted for 295 d. Mice of C57BL/6J background inoculated as
      juveniles had detectable viral DNA in large intestinal content and tissues for 24
      d after inoculation and an antibody response that persisted for 288 d. However,
      viral DNA was not detected in tissues of C57BL/6J mice inoculated as adults,
      although an antibody was detected for 111 d after inoculation; these results
      suggest probable viral replication in adult C57BL/6J mice but at levels below the
      limits of detection. BALB/cArc mice inoculated as juveniles or adults had
      detectable virus DNA in tissues for 108 to 242 d after inoculation, but no
      antibody was detected. Similarly, BALB/c-Foxn1(nu)/Arc mice had detectable levels
      of viral DNA in tissues for 98 to 131 d but no measurable antibody. The
      difficulty of detecting antibody in mice with a BALB/c background indicates they
      are unsuitable for routine surveillance of MPV1f infection.

PMID- 20819391
TI  - Comparison of carbon dioxide and argon euthanasia: effects on behavior, heart
      rate, and respiratory lesions in rats.
AB  - In this study we compared rat (n = 16) responses to euthanasia with either
      gradual-fill CO(2) or rapid induction argon gas by evaluating the animals' heart
      rate via radiotelemetry, behavior, and vocalizations. We also evaluated the
      histologic effects of the gases. Rats were placed in an open test chamber 24 h
      before the start of the experiment. During baseline tests, rats were exposed to
      oxygen to evaluate the effects of the noise and movement of gas entering the
      chamber; 1 wk later, rats were euthanized by gas displacement with either 10%/min
      CO(2) or 50%/min argon gas. Rats tended to have higher heart rats and were more
      active during the baseline test, but these parameters were normal before the
      euthanasia experiment, suggesting that the rats had acclimated to the equipment.
      Heart rate, behavior, and ultrasonic vocalizations were recorded for 2 min after
      gas introduction in both groups. All rats appeared conscious throughout the test
      interval. The heart rates of rats exposed to argon did not change, whereas those
      of rats exposed to CO(2) declined significantly. Unlike those exposed to CO(2),
      rats euthanized with argon gas gasped and demonstrated seizure-like activity.
      There were no differences in the pulmonary lesions resulting from death by either
      gas. Our results suggest that argon as a sole euthanasia agent is aversive to
      rats. CO(2) using a 10%/min displacement may be less aversive than more rapid
      displacements. Future research investigating methods of euthanasia should allow
      sufficient time for the rats to acclimate to the test apparatus.

PMID- 20819392
TI  - Anesthesia with intraperitoneal propofol, medetomidine, and fentanyl in rats.
AB  - A safe and reliable method for anesthetizing rats has long been a leading concern
      of biomedical researchers. We recently found that the intraperitoneal
      administration of propofol combined with medetomidine and fentanyl is safe for
      mouse anesthesia. Here we studied whether the same combination could be used for
      general anesthesia in rats. We used male Wistar rats to test 10 combinations of
      propofol, medetomidine, and fentanyl administered intraperitoneally and reversed
      with intraperitoneal atipamezole 30 min after induction. The depth of anesthesia,
      induction time, loss of pedal withdrawal reflex, pulse rate, and respiratory rate
      were evaluated, along with the duration and quality of induction, surgical
      anesthesia, and recovery. The combination of propofol and medetomidine provided a
      predictable induction and sufficient hypnosis and muscle relaxation, but surgical
      anesthesia (loss of pedal withdrawal reflex) was difficult to achieve with this
      protocol. The addition of fentanyl increased analgesia, making it possible to
      achieve surgical anesthesia. In conclusion, combination of propofol (100 mg/kg),
      medetomidine (0.1 mg/kg), and fentanyl (0.1 mg/kg) is a safe and practical
      technique for intraperitoneal anesthesia in rats, providing a surgical window of
      25 min and restraint for 30 min, with rapid recovery after administration of
      atipamezole.

PMID- 20819393
TI  - Eugenol anesthesia in African clawed frogs (Xenopus laevis) of different body
      weights.
AB  - The objective of this prospective study was to determine the duration of
      anesthesia in Xenopus laevis frogs of different body weights relative to exposure
      time in a eugenol (350 microL/L) bath. Two groups of 5 female frogs each weighing
      7.5 +/- 2.1 g (small frogs) or 29.2 +/- 7.4 g (medium frogs) were used. The
      acetic acid test (AAT), withdrawal reflex, righting reflex, heart rate, and blood
      oxygen saturation were used to evaluate CNS depression after eugenol bath
      administration. No responses to the AAT, withdrawal reflex, and righting reflex
      were seen for 1 h (small frogs) or 0.5 h (medium frogs) after immersion in a
      eugenol bath for 5 or 10 min, respectively. Oxygen saturation was not affected by
      anesthesia, but heart rate was depressed for as long as 1 h in both groups of
      frogs. Surgical anesthesia evaluated by using skin and abdominal incisions
      revealed that small frogs were anesthetized for a maximum of 15 min compared with
      30 min in medium frogs. Frogs showed no ill effects 24 h after eugenol bath
      administration. These results suggest that body weight is an important parameter
      to consider when using a eugenol bath for anesthesia of Xenopus frogs.

PMID- 20819394
TI  - Comparison of telemetry and high-definition oscillometry for blood pressure
      measurements in conscious dogs: effects of torcetrapib.
AB  - This study compared torcetrapib-induced blood pressure (BP) changes
      simultaneously obtained by high-definition oscillometry (HDO) and telemetry. Male
      beagles (n = 6) received single oral doses of vehicle or torcetrapib at 10 or 30
      mg/kg; BP were acquired simultaneously by HDO and telemetry from 2 h before
      dosage until 7 h afterward. Systolic, diastolic, and mean arterial pressures
      (MAP) and heart rate were compared by using Altman-Bland agreement analysis. Dogs
      were allocated into subgroups according to temperament and baseline MAP (less
      than 110 mm Hg and 110 mm Hg or greater). Both methods demonstrated high
      precision. HDO recordings exhibited higher variability for all parameters
      (inclusive MAP SDs were 7.0 +/- 2.7 mm Hg for HDO compared with 3.4 +/- 1.9 mm Hg
      for telemetry), accompanied by a positive bias for all pressures (systolic, 10.4
      mm Hg; diastolic, 5.7 mm Hg; MAP, 1.9 mm Hg). Both methods detected similar
      maximal increases in MAP with 30 mg/kg torcetrapib (HDO, 15.8 +/- 10.4 mm Hg;
      telemetry, 15.8 +/- 5.3 mm Hg). No significant effects were noted for heart rate.
      Torcetrapib elicited a dose-dependent increase in BP in dogs with baseline MAP of
      less than 110 mm Hg, whereas increases were maximal with 10 mg/kg in the other
      group, and dose-dependence was no longer observed. BP changes were influenced by
      animal temperament, demonstrating that HDO results must be interpreted with
      caution. HDO may provide a useful and accurate method for noninvasive BP
      measurements in canine studies.

PMID- 20819395
TI  - Surgical approaches to vascular access for large-caliber devices in preclinical
      research models.
AB  - Percutaneous vascular access options in preclinical models are often smaller than
      the relevant structures in humans or undersized for early-prototype research
      devices. Here we describe the surgical approaches and results for surgical
      vascular access sites in preclinical swine and sheep models. Fourteen adult
      miniature swine underwent successful 18-French vascular access by means of
      thoracotomy to the brachiocephalic artery. In addition, 11 swine and 10 sheep
      underwent successful 22-French vascular access by means of retroperitoneal
      laparotomy to the abdominal aorta. The relevancy of approach angles and vessel
      tortuosity should be considered when selecting appropriate preclinical models and
      techniques. The techniques described are effective for delivery of large-caliber
      devices in preclinical testing.

PMID- 20819396
TI  - Modified skin-window technique in cynomolgus macaques (Macaca fasicularis) for
      assessing neutrophil extravasation.
AB  - Alterations in neutrophil extravasation are seen in disease states and in
      response to therapeutics. To investigate neutrophil extravasation during the
      acute inflammatory response, a skin-window technique used in humans was adapted
      for use in cynomolgus macaques (Macaca fasicularis). Modulation of neutrophil
      extravasation was attempted with systemic methotrexate and local application of
      the anaphylatoxin recombinant C5a (rC5a). On day 1, skin windows were created in
      4 ketamine-anesthetized monkeys on both forearms by mildly abrading the skin and
      then overlaying the abrasions with filter paper either saturated in saline or
      rC5a for 6 h. At 2.5 h prior to generation of new skin windows on day 2, the
      monkeys received 4.5 mg methotrexate IM, and skin windows and treatment with
      saline or rC5a were repeated on new forearm sites on each monkey. All papers were
      analyzed for albumin, neutrophil number, and the neutrophil chemoattractant IL8.
      Day 1 albumin levels did not differ between groups, indicating consistent
      abrasion. Methotrexate given prior to the day 2 abrasions reduced neutrophil
      extravasation and IL8 levels compared with those on day 1. rC5a partially
      abrogated the methotrexate-induced reduction in neutrophil extravasation and IL8
      production. The skin-window technique was well tolerated by the monkeys and
      successfully accommodated measurement of changes in neutrophil extravasation in
      response to inflammatory modulators.

PMID- 20819397
TI  - Spontaneous Staphylococcus xylosus infection in mice deficient in NADPH oxidase
      and comparison with other laboratory mouse strains.
AB  - Staphylococcus xylosus typically is described as a nonpathogenic common
      inhabitant of rodent skin. Reports of S. xylosus as a primary pathogen in human
      and veterinary medicine are scarce. Here we report 37 cases, affecting 12 strains
      of laboratory mice, of spontaneous infections in which S. xylosus was isolated
      and considered to be the primary pathogen contributing to the death or need for
      euthanasia of the animal. Infection with S. xylosus was the major cause of death
      or euthanasia in 3 strains of mice deficient in the production of phagocyte
      superoxide due to defects in NADPH oxidase. NADPH-oxidase-deficient mice (n = 21)
      were most susceptible to spontaneous S. xylosus infections. The infections were
      characterized by abscesses and granulomas in soft tissues, with bacterial
      migration to internal organs (primarily regional lymph nodes and lungs and, to a
      lesser degree, muscle, bone, and meninges). In contrast, 9 strains of phagocyte
      superoxide-producing mice (n = 16) also had S. xylosus infections, but these were
      largely confined to eyelids, ocular conjunctiva, and skin and rarely involved
      other tissues or organs. Because exhaustive bacterial culture and isolation may
      not be performed routinely from mouse abscesses, S. xylosus infections may be
      underdiagnosed. S. xylosus should be considered in the differential diagnosis in
      laboratory mice with abscesses and other skin lesions. This report expands the
      range of mouse strains and tissues and organs susceptible to spontaneous S.
      xylosus infection and compares the pathology among various mice strains.

PMID- 20819398
TI  - Pediculosis in two research ponies (Equus caballus).
AB  - Horses and ponies are used infrequently in research but may be valuable animal
      models for studying both equine-specific diseases and biomedical applications. We
      report here 2 cases of pediculosis in random-source ponies. Infestation and
      clinical signs were not present during a 4-wk quarantine period or for 3 to 9 mo
      thereafter but became apparent coincident with the ponies' movement from pasture
      to indoor housing. These 2 geldings presented with pruritus associated with
      excoriating lesions on the neck, and infestation with Bovicola (Werneckiella)
      equi Denny, 1842 was diagnosed. Ponies were treated successfully with standard
      wound care and a spray containing 2.0% permethrin and 0.05% pyriproxyfen. These
      cases highlight the importance of recognizing the possibility of louse
      infestation, even in healthy, well-cared-for animals, and the need for personnel
      to be aware of early behavioral signs of infestation, such as rubbing and
      agitation.

PMID- 20819399
TI  - Impact of platelet transfusion on hematoma expansion in patients receiving
      antiplatelet agents before intracerebral hemorrhage.
AB  - OBJECTIVES: Patients receiving antiplatelet medications are reported to be at
      increased risk for hematoma enlargement and worse clinical outcomes following
      intracerebral hemorrhage (ICH). While platelet transfusions are frequently
      administered to counteract qualitative platelet defects in the setting of ICH,
      conclusive evidence in support of this therapeutic strategy is lacking. In fact,
      platelet transfusions may be associated with adverse effects, and represent a
      finite resource. We sought to determine the clinical efficacy of platelet
      transfusion and its impact on systemic complications following ICH in a cohort of
      patients receiving antiplatelet medications. METHODS: We retrospectively analysed
      the medical records of 66 patients admitted to our institution from June 2003 to
      July 2008 who suffered a primary ICH while receiving antiplatelet
      (acetylsalicylic acid and/or clopidogrel) therapy. The primary outcome was the
      rate of significant (>25% increase from admission) hematoma expansion in
      transfused (n=35) versus non-transfused (n=31) patients. Discharge modified
      Rankin score (mRS) and the rates of systemic complications were also assessed.
      RESULTS: There were no statistically significant differences in rates of hematoma
      expansion between cohorts, nor were there differences in demographic variables,
      systemic complications or discharge mRS. Subgroup analysis revealed that there
      was a higher rate of hematoma expansion in the clopidogrel cohort (p=0.034) than
      in the cohort of patients receiving aspirin alone. DISCUSSION: This study
      suggests that platelet administration does not reduce the frequency of hematoma
      expansion in ICH patients receiving antiplatelet medications. This lack of
      efficacy may relate to transfusion timing, as a significant proportion of
      hematoma expansion occurs within 6 hours post-ictus. Additionally, the increased
      rates of hematoma expansion in the clopidogrel cohort may relate to its prolonged
      half-life. A larger, prospective study is warranted.

PMID- 20819400
TI  - Comparison of retention and demineralization inhibition potential of adhesive
      banding cements in primary teeth.
AB  - PURPOSE: The purpose of this study was to evaluate the efficacy of banding
      cements in terms of retentive capability and demineralization inhibition
      potential. METHODS: We included 48 non-carious primary mandibular second molar
      teeth. Preformed stainless steel bands were adapted onto the teeth. All teeth
      were randomly assigned to four groups: Group I (Adaptation of bands without
      cementation), Group II (Cementation of bands using conventional Glass Ionomer
      Cement), Group III (Cementation of bands using Resin-modified Glass Ionomer
      Cement), Group IV (Cementation of bands using Resin cement), and placed in
      artificial saliva. Each day, specimens were taken from artificial saliva and
      suspended in an artificial caries solution for 35 minutes, every 8 hours. At the
      end of 3 months, retention of bands was estimated using an Instron Universal
      Testing Machine. The mode of failure was recorded and specimens were sectioned
      and examined under polarized microscope for demineralized lesions. RESULTS: The
      mean retention value was highest with resin cement, followed by RMGIC, GIC, and
      Control group respectively. The RMGIC group showed more favorable modes of
      failures. All the experimental groups showed significant demineralization
      inhibition potential. CONCLUSION: RMGIC is the preferable banding cement and can
      be used effectively to cement bands in primary dentition.

PMID- 20819401
TI  - Cytotoxic effects of primary tooth root canal filling materials on L929 cell
      line.
AB  - PURPOSE: The purpose of this study was to determine the cytotoxic effects of five
      different primary tooth root canal filling materials on L929 permanent cell line
      with MTT assay. METHODS: Kri 1 paste (iodoform), Diapex (iodoform+Ca(OH)(2)),
      Metapaste (Ca(OH)(2) with distilled water), Dentalis (iodoform+ZOE+Ca(OH)(2)) and
      Kalsin (Ca(OH)(2) with glycerin) were used in this study. Tested materials were
      in contact for 24, 48 and 72 hours with L929 cells. At the end of the test
      periods, MTT test solutions were added to the plates and incubated for 3 hours at
      37 degrees C. Then optic densities were read using UV visible spectrophotometer.
      All assays were repeated three times to ensure reproducibility. The obtained data
      were analyzed statistically by one-way analysis of variance and Dunnett T3 post
      hoc test (P<0.05). RESULTS: All tested materials were found cytotoxic on L929
      cell line. It was found that Kri 1 paste group showed the highest survival rates.
      CONCLUSIONS: We concluded that the use of Kri 1 paste as a root canal filling
      material is a better option than other medications in primary teeth. Further
      research is necessary to determine the effect of root canal filling materials on
      vital tissues.

PMID- 20819402
TI  - Nanohydroxyapatite used as a pulpotomy and direct pulp capping agent in primary
      pig teeth.
AB  - PURPOSE: Recently, a fully Nanocrystalline Hydroxyapatie (NHA) paste has been
      introduced for augmentation procedures in osseous defects and is attracting
      increasing interest in medicine and dentistry. The purpose of the present study
      was to assess and compare the pulp response of pig primary teeth after capping
      with NHA and formocresol in pulpotomy and NHA and calcium hydroxide in direct
      pulp capping. METHODS: Forty teeth of two 4-month old pigs were pulpotomized and
      capped with these materials. Four weeks later, the animals were euthanized and
      the specimens were prepared for histological examination. RESULTS: In the
      pulpotomy groups, there was a significant difference between NHA and FC in terms
      of pulp response, hard tissue formation and normal pulp tissue preservation. In
      the direct pulp capping groups, there was no significant difference between NHA
      and Ca(OH)2 in terms of criteria mentioned above. CONCLUSIONS: The results of the
      present histological study show that, in the short term and in non-carious pig
      teeth, NHA appears to be biocompatible and provokes no moderate or severe
      inflammatory reaction in pulp tissue in both pulpotomy and direct pulp capping
      treatments.

PMID- 20819403
TI  - Dental care in children with developmental disabilities: attention deficit
      disorder, intellectual disabilities, and autism.
AB  - The Federal government reports that 13% of Americans between birth and 18 years
      of old meet the definition of a child with special health care needs. These
      children and young adults present unique challenges for both pediatric and
      general dentists to provide access to the oral health care system--establishing a
      treatment plan for those with unique medical, behavioral and dental needs and
      maintaining oral health over the lifetime. The purpose of this article was to
      describe the characteristics of 3 common developmental disabilities and the
      challenges these issues present to the oral health care practitioner.

PMID- 20819404
TI  - Three-and-a-half-year clinical evaluation of posterior composite resin in
      children.
AB  - PURPOSE: To evaluate the clinical performance of a packable composite resin
      (Tetric Ceram HB) for posterior restorations of children after 3.5 years,
      according to Ryge criteria. METHODS: Twenty five open apex molar teeth with
      extensive caries in 21 Iranian patients (8.2 year mean age) were restored by one
      operator. After caries removal, a layer of calcium hydroxide and glass ionomer
      base, Fuji II LC were applied. The teeth were restored using an adhesive system,
      Excite, and flowable composite, Tetric-Flow. The cavities were then restored
      incrementally with a Tetric Ceram HB. All the 25 restorations were evaluated
      after 3.5 years by two independent evaluators. Statistical analysis was performed
      using McNemar test. RESULTS: Surface texture for all restorations was classified
      as excellent. There were no evidence of secondary caries and bulk fracture in any
      of the restorations. Regarding the items of anatomical form and marginal
      integrity the statistical analysis reveled a significant difference between the
      baseline and recall scores respectively (P=0.031 and P=0.031). CONCLUSIONS: It
      was concluded that Tertic Ceram HB exhibited excellent clinical performance after
      3.5 years in the open apex first permanent molar teeth.

PMID- 20819405
TI  - Nonsyndromic multiple mandibular supernumerary premolars: a case report.
AB  - Supernumerary teeth are generally asymptomatic and may not become visible
      radiographically until a patient's normal teeth have erupted. Moreover,
      diagnosing, treating, and following up supernumerary teeth appropriately with
      radiographic images is important. In this case report, we present radiographic
      images, including three-dimensional computerized tomography films, of a 13-year
      old patient with four nonsyndromic mandibular supernumerary premolars, and the
      surgical treatment.

PMID- 20819406
TI  - Oral manifestations and treatment of a child with Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is a chronic inflammatory systemic autoimmune disease
      affecting the exocrine, salivary and lacrimal glands. The condition occurs more
      often in adults and is rare in childhood. SS should be considered in the
      differential diagnosis of recurrent parotitis and keratoconjunctivitis sicca.
      Oral manifestations include early tooth decay and xerostomia. Treatment consists
      of operative dentistry and saliva management. This paper reports a case of a 10
      year-old Brazilian boy with SS, stressing the oral manifestations, treatment
      conduct, clinical importance and need for an early diagnosis in order to improve
      the patient's quality of life.

PMID- 20819407
TI  - Delayed eruption of maxillary permanent central incisors due to bilateral
      tuberculate supernumerary teeth: case report.
AB  - The purpose of this case report is to discuss the delayed eruption of permanent
      maxillary central incisors in a 10-year-old boy with retained primary maxillary
      central incisors. Radiological investigations revealed the presence of impacted
      bilateral supernumerary teeth and impacted permanent incisors. These
      supernumerary teeth were surgically removed and were diagnosed as tuberculate
      type. The patient is on clinical and radiological follow up for spontaneous
      eruption of the permanent teeth.

PMID- 20819408
TI  - Camouflage treatment for class III malocclusion combined with traction of an
      impacted maxillary central incisor.
AB  - This case report describes the treatment of a patient with an unerupted maxillary
      left central incisor, class III malocclusion with crossbite of the maxillary
      posterior teeth and lateral open bite. Treatment consisted of rapid maxillary
      expansion followed by anterior space opening, maxillary protraction and traction
      of the unerupted teeth with a light force system. Favorable results were obtained
      in terms of correcting incisor position and class III malocclusion. The results
      achieved remained stable throughout a 4-year retention period.

PMID- 20819409
TI  - Severe root resorption associated with ectopically erupting teeth: a case report.
AB  - A 12-year-old Japanese boy had ectopic eruption of the permanent maxillary
      canines and permanent mandibular second molars accompanied by root resorption of
      the adjacent permanent teeth. The permanent maxillary lateral incisors were
      extracted, and fenestration traction treatment was performed for the ectopically
      erupting canines. They were moved to the occlusal position orthodontically using
      a lingual arch appliance and sectional arch wire. The mandibular second molars
      were moved distally with an appliance designed to minimize the load on the teeth.
      The treatment is discussed with consideration of the diagnosis and appliances.

PMID- 20819410
TI  - Non-thermal cellular effects of lowpower microwave radiation on the lens and lens
      epithelial cells.
AB  - Because of the increased use of modern radiofrequency devices, public concern
      about the possible health effects of exposure to microwave radiation has arisen
      in many countries. It is well established that high-power microwave radiation can
      induce cataracts via its thermal effects. It remains unclear whether low-power
      microwave radiation, especially at levels below the current exposure limits, is
      cataractogenic. This review summarizes studies on the biological effects of low
      power microwave radiation on lens and lens epithelial cells (LECs). It has been
      reported that exposure affects lens transparency, alters cell proliferation and
      apoptosis, inhibits gap junctional intercellular communication, and induces
      genetic instability and stress responses in LECs. These results raise the
      question of whether the ambient microwave environment can induce non-thermal
      effects in the lens and whether such effects have potential health consequences.
      Further in vivo studies on the effects on the lens of exposure to low-power
      microwave radiation are needed.

PMID- 20819411
TI  - Early diagnosis of oral cancer.
AB  - Survival rates for oral cancer are very poor, at approximately 50% overall, and
      have not improved markedly in recent decades despite advances in therapeutic
      interventions. Detecting oral cancer at an early stage is believed to be the most
      effective means of reducing rates of death, morbidity and disfigurement from this
      disease. Tobacco and alcohol consumption and pre-malign lesions are the most
      common aetiological factors. The proportion of patients presenting with oral
      cancer at an advanced stage is troubling. Early diagnosis is the most effective
      way of reducing the individual burden of the disease, decreasing morbidity and
      mortality and improving quality of life. For early diagnosis, healthcare
      providers should perform oral cancer examinations as part of their patient care
      regime, and need to be knowledgeable about early signs of oral carcinoma. Oral
      cancer awareness among the public should also be improved.

PMID- 20819412
TI  - Scientific publications in pharmacology and pharmacy journals from Chinese
      authors in various parts of North Asia: a 10-year survey of the literature.
AB  - The amount and quality of pharmacology and pharmacy research by authors from
      China was investigated by comparing published articles from 136 international
      journals (1998 - 2007) by authors from mainland China, Hong Kong and Taiwan. The
      number of articles, clinical trials, randomized controlled trials, case reports,
      impact factors, number of citations and number of articles published in top
      general medicine journals were compared. The total number of articles increased
      significantly between 1998 and 2007 (from 324 to 2536 per year). In total, there
      were 12 021 articles: 7576 from mainland China, 3267 from Taiwan and 1178 from
      Hong Kong. The accumulated impact factor of the articles from mainland China (16
      688.94) was much higher than for those from Taiwan (8726.92) and Hong Kong
      (3161.22) but, among the three regions, Hong Kong had the highest mean impact
      factor and the most articles published in top general medicine journals.

PMID- 20819413
TI  - Tumour necrosis factor-alpha polymorphisms and hepatocellular carcinoma: a meta
      analysis.
AB  - The genetic basis of susceptibility to hepatocellular carcinoma (HCC) is poorly
      understood. To summarize the quantitative association between polymorphisms of
      the tumour necrosis factor-alpha (TNFA) gene and HCC, a meta-analysis of relevant
      studies was performed. Ten case-control studies involving 1421 HCC cases were
      identified from the Medline, Embase and Current Contents databases. Combined
      results based on all studies showed that patients with HCC had a significantly
      lower frequency of the TNFA gene polymorphism -308GG than healthy controls. When
      stratifying for race, results were similar among Asians and Caucasians. When
      comparing with hepatitis B virus infection cases, no statistical association was
      found. This meta-analysis suggests that TNFA -308GG gene polymorphism is
      associated with a modest decrease in the risk of HCC.

PMID- 20819414
TI  - Impaired mitochondrial oxidative phosphorylation in multiple insulin-sensitive
      tissues of humans with type 2 diabetes mellitus.
AB  - Alteration of mitochondrial oxidative phosphorylation (OXPHOS) may contribute to
      insulin resistance. It is unclear, however, which characteristics are common to
      insulin-sensitive tissues. Using an oligonucleotide microarray and quantitative
      real-time polymerase chain reaction, the gene expression profiles of skeletal
      muscle, visceral adipose tissue and liver from autopsy donors with and without
      type 2 diabetes mellitus were determined. Common dysregulated genes were enriched
      in mitochondrial OXPHOS, and most of these genes were down-regulated in both the
      skeletal muscle and visceral adipose tissue of diabetic subjects, but up
      regulated in diabetic liver. Messenger RNA (mRNA) for peroxisome proliferator
      activated receptor-gamma co-activator 1alpha was significantly increased in
      diabetic liver but significantly reduced in diabetic skeletal muscle. Tumour
      necrosis factor-alpha mRNA was significantly down-regulated in diabetic visceral
      adipose tissue. The mitochondrial DNA content was slightly, though not
      significantly, reduced in diabetic liver and diabetic skeletal muscle. It is
      concluded that defects in OXPHOS genes and individual transcription co-factors in
      insulin-sensitive tissues may play an important role in the development of type 2
      diabetes and the insulin-resistant state.

PMID- 20819415
TI  - Resistance exercise did not alter intramuscular adipose tissue but reduced
      retinol-binding protein-4 concentration in individuals with type 2 diabetes
      mellitus.
AB  - Lipid accumulation in muscle is associated with diminished insulin sensitivity.
      It was hypothesized that resistance exercise decreases muscular adipose tissue
      and reduces the level of retinol-binding protein-4 (RBP4), which is linked to
      adipose tissue and insulin sensitivity in diabetics. Forty-four women with type 2
      diabetes were randomly assigned to three groups for a period of 12 weeks: control
      (asked to maintain a sedentary lifestyle); resistance exercise (elastic band
      exercise at moderate intensity five times per week); and aerobic exercise
      (walking for 60 min at moderate intensity five times per week). Subcutaneous
      (SCAT), subfascial (SFAT) and intramuscular (IMAT) adipose tissues at mid-thigh
      level were assessed using computed tomography, and RBP4 level and insulin
      sensitivity (fractional disappearance rate of insulin, k(ITT)) were assessed
      before and after intervention. Changes in SCAT, SFAT, IMAT, RBP4 and k(ITT) were
      similar among the three groups. Within-group analysis revealed that body mass
      index and waist circumference decreased significantly in both exercise groups,
      but RBP4 decreased significantly only with resistance exercise. Resistance
      exercise did not alter muscular adipose tissue or improve insulin sensitivity.

PMID- 20819416
TI  - Adiponectin levels in non-obese first-degree relatives of type 2 diabetes
      patients and non-diabetic subjects: a 5-year follow-up study.
AB  - This study was designed to investigate adiponectin levels and their relationship
      to various parameters at baseline and after 5 years in non-obese first-degree
      relatives of type 2 diabetes patients (FDR group) versus subjects without a
      family history of diabetes (normal group). Adiponectin levels at baseline were
      lower in the FDR group versus the normal group. After 5 years, adiponectin levels
      had fallen significantly in both the FDR (24.3% reduction) and the normal (35.7%
      reduction) groups. Adiponectin levels were negatively correlated with waist/hip
      ratio, fasting plasma glucose, carotid intima-media thickness (IMT) and insulin
      resistance in the FDR group. When adjusted for relevant risk factors, adiponectin
      was associated with age, high-density lipoprotein-cholesterol and IMT; these
      factors explained 45% of the variation in adiponectin in the FDR group. In the
      normal group, multiple regression analyses revealed that low-density lipoprotein
      cholesterol and IMT explained 25% of the variability in the adiponectin
      concentration. In both groups, however, the correlation between adiponectin and
      IMT just failed to reach statistical significance in this population group. We
      conclude that adiponectin levels were reduced in non-obese first-degree relatives
      of patients with type 2 diabetes and normal individuals over a 5-year period.
      This study supports previous findings that hypoadiponectinaemia is a risk factor
      for atherosclerosis.

PMID- 20819417
TI  - Assessment of transvaginal sonography combined with endometrial cytology as a
      mass screening method for endometrial cancer in Beijing.
AB  - This was a two-phase, large sample-group study assessing the effectiveness of
      combined transvaginal sonography (TVS) and endometrial cytology in endometrial
      cancer screening. In phase one, 3308 women without known cancer were enrolled and
      TVS was performed on those with symptoms or endometrial cancer risk factors.
      Endometrial cytology was carried out on post-menopausal women with endometrial
      thickness >or= 5 mm and on pre-menopausal women with endometrial thickness >or=
      10 mm. Dilation and curettage (D & C) was performed if cytological findings were
      inconclusive, or indicated cancer or pre-cancer. The mass screening safety
      interval is at least 2 years and phase two was carried out 2 years after phase
      one, using the same procedures, on the 3305 women who were originally found to be
      cancer free. Combined TVS and endometrial cytology resulted in 100% sensitivity
      and 99.0% specificity, reducing unnecessary D & C by 91.7% and screening costs by
      20.1%. Combined TVS examination and endometrial cytology decreased potentially
      harmful examinations, patient suffering and medical costs, and is worth
      considering for broad implementation.

PMID- 20819418
TI  - Mutations in the beta-myosin heavy chain gene in southern Chinese families with
      hypertrophic cardiomyopathy.
AB  - In this study, 14 unrelated hypertrophic cardiomyopathy (HCM) probands were
      scanned by polymerase chain reaction-single-strand conformation polymorphism
      analysis and DNA sequencing. Three mis-sense mutations of the beta-myosin heavy
      chain gene, MYH7, were found: valine (Val) 606 methionine (Met), arginine (Arg)
      694 leucine (Leu), and Arg 723 glycine (Gly). All are reported here for the first
      time in Chinese subjects. The results showed that: Val606Met is an intermediate
      malignancy mutation; Arg694Leu is a novel mutation with a benign phenotype; and
      the Arg723Gly mutation is linked to malignancy - it can lead not only to HCM but
      also to dilated cardiomyopathy at various ages. The clinical symptoms associated
      with Arg723Gly emerged early and caused more severe clinical manifestation and
      poorer prognosis in females than in males. Mis-sense mutations were not detected
      in the myosin binding protein C, cardiac, cardiac troponin T type 2, or cardiac
      troponin I type 3 genes. The MYH7 gene may be an HCM mutation hotspot in the
      Chinese and have unique features in this study population.

PMID- 20819419
TI  - Intraperitoneal ropivacaine for effective pain relief after laparoscopic
      appendectomy: a prospective, randomized, double-blind, placebo-controlled study.
AB  - This prospective, randomized, doubleblind, placebo-controlled study evaluated the
      effectiveness of intraperitoneal instillation of ropivacaine in the relief of
      pain in patients undergoing laparoscopic appendectomy. Patients in group C
      (placebo control group; n = 33) received normal saline and those in group I
      (instillation group; n = 30) received an instillation of 2 mg/kg ropivacaine at
      the initiation of the pneumoperitoneum. Visual analogue scale pain scores,
      fentanyl consumption and the frequency at which patients pushed the button (FPB)
      of a patient-controlled analgesia system during the post-operative period were
      significantly lower in group I compared with group C, and decreased gradually
      with time in both groups. The total amount of fentanyl consumed and the total FPB
      were significantly lower in group I compared with group C. Thus, intraperitoneal
      ropivacaine instillation reduced pain during the post-operative period after
      laparoscopic appendectomy. In addition, this drug was easy to administer and had
      no adverse effects at the dose used.

PMID- 20819420
TI  - Validity of proxy data obtained by different psychological autopsy information
      reconstruction techniques.
AB  - Two informants were interviewed for each of 416 living controls (individuals
      sampled from the normal population) interviewed in a Chinese case-control
      psychological autopsy study. The validity of proxy data, obtained using seven
      psychological autopsy information reconstruction techniques (types 1, 2 and A -
      E), was evaluated, with living controls' self reports used as the gold-standard.
      Proxy data for reconstruction technique types 1, 2 and D on the Impulsivity
      Inventory Scale (total impulsivity score) were no different from the living
      controls' self report gold standard, whereas data for types A and E were smaller
      than data from living controls. On the 'acceptance or resignation' sub-scale of
      the avoidance coping dimension of the Moos Coping Response Inventory, information
      obtained by reconstruction technique types 1 and D was not significantly
      different from the living controls' self reports, whereas proxy data from types
      2, A and E were smaller than those from the living controls. No statistically
      significant differences were identified for other proxy data obtained by
      reconstruction technique types 1, 2, A, D and E. These results indicate that
      using a second informant does not significantly enhance information
      reconstruction for the target.

PMID- 20819421
TI  - Evaluation of the antiobesity effects of an amino acid mixture and conjugated
      linoleic acid on exercising healthy overweight humans: a randomized, double
      blind, placebo-controlled trial.
AB  - This single-centre, randomized, double-blind, placebo-controlled trial
      investigated the effects of administering a mixture of four amino acids (lysine,
      proline, alanine and arginine) with or without conjugated linoleic acid to
      healthy overweight humans before and after exercising. Forty-one healthy subjects
      (body mass index >or= 23 to < 30 kg/m(2)) completed the study following
      randomization to receive either placebo or one of three test supplements: amino
      acid mixture 0.76 g/day; amino acid mixture 1.52 g/day; or amino acid mixture
      1.52 g/day coadministered with conjugated linoleic acid 1.6 g/day. Each of the
      study treatments was administered 30 min before and immediately after a period of
      daily exercise, which was delivered by an exercise expert, for a period of 12
      weeks. When compared with the placebo group, several indicators, such as waist
      and hip circumferences, were found to have significantly decreased in the test
      supplement groups compared with the placebo. These results suggest that ingestion
      of these supplements might enhance the fat-burning effects of exercise.

PMID- 20819422
TI  - Common carotid artery intima-media thickness is not increased but distensibility
      is reduced in normotensive patients with type 2 diabetes compared with control
      subjects.
AB  - This study evaluated carotid artery parameters in normotensive patients with type
      2 diabetes compared with non-diabetic control subjects. Using a high-resolution B
      mode ultrasound scanner, common carotid artery intima-media thickness (IMT) and
      carotid tree atheroma thickness were measured in 82 patients with type 2 diabetes
      and 41 controls. The distensibility of the common carotid artery was calculated
      using the Reneman equation. Distensibility was significantly decreased and
      atheroma thickness was significantly increased in the diabetes group. There was
      no significant difference in IMT between the two groups. Stepwise linear
      regression analysis revealed an association between common carotid artery
      distensibility and post-ischaemic dilatation of the brachial artery (a measure of
      endothelial function), body mass index and diabetes duration in patients with
      type 2 diabetes. In conclusion, common carotid artery IMT in normotensive
      patients with type 2 diabetes is comparable to that of control subjects, whereas
      atheroma thickness is higher and arterial stiffness more pronounced in those with
      type 2 diabetes, indicating the existence of atherosclerotic changes in
      normotensive type 2 diabetes patients.

PMID- 20819423
TI  - Variants in the dihydropyrimidine dehydrogenase, methylenetetrahydrofolate
      reductase and thymidylate synthase genes predict early toxicity of 5-fluorouracil
      in colorectal cancer patients.
AB  - Adverse drug reactions to 5-fluorouracil (5-FU)-based chemotherapy have been
      reported to be due, in part, to genetic variants of the genes for the drug
      related enzymes thymidylate synthase (TS; TYMS gene), methylenetetrahydrofolate
      reductase (MTHFR gene) and dihydropyrimidine dehydrogenase (DPD; DPYD gene). This
      study investigated whether selected genetic variants of the TYMS, MTHFR and DPYD
      genes predict 5-FU-related early toxicity. The prevalence of the genetic variants
      was determined in 122 colorectal cancer patients and in a reference population of
      320 blood donors. Subgroup analysis of 68 of the colorectal cancer patients was
      carried out to determine the relationship between selected gene variants detected
      in peripheral mono nuclear cells and tolerability during the first or second
      cycle of 5-FU based treatment. Toxicity was linked to the TYMS 2R/2R variant
      (relative risk [RR] 1.66; sensitivity 0.37; specificity 0.77) and to the MTHFR
      c1298 C/C genetic variant (RR 1.77; sensitivity 0.17; specificity 0.91). Patients
      with the genetic variant IVS14+1 G/A or c1896 C/T in the DPYD gene had a
      statistically significant increased risk of experiencing toxicity (RR 2 and 6,
      respectively), both having a high specificity (0.97 and 0.98, respectively) and
      low sensitivity (0.04 and 0.13, respectively). It is concluded that pre-treatment
      detection of genetic variants can help to predict early toxicity experienced by
      patients receiving 5-FU-based chemotherapy.

PMID- 20819424
TI  - Assessment of serum antioxidant status in patients with silicosis.
AB  - Prolonged exposure to silica dust causes an imbalance in the generation of free
      radicals and in the antioxidant system, thereby inducing oxidative stress. The
      antioxidant status of 113 silicosis patients and 116 control subjects without
      silicosis was examined. Serum superoxide dismutase (SOD) activity and serum
      levels of malondialdehyde (MDA) and glutathione (GSH) were significantly higher
      in silicosis patients than in controls. The GSH level in patients with stage I
      silicosis was higher than that in patients with other stages, but there was no
      difference in serum MDA level and SOD activity between disease stages. The GSH
      level of patients who worked with air drills was significantly lower than that of
      patients in other occupations, whereas the MDA level was significantly elevated
      in patients who used air drills. Serum SOD activity did not differ significantly
      according to the occupational group. It is concluded that the measurement of
      serum SOD, GSH and MDA levels could be beneficial in the clinical evaluation of
      serum antioxidant status in silicosis patients.

PMID- 20819425
TI  - Mini-subvastus versus a standard approach in total knee arthroplasty: a
      prospective, randomized, controlled study.
AB  - This prospective randomized study compared the clinical and radiological results
      of primary total knee arthropasty (TKA) using a mini-subvastus approach (group I;
      n = 35) or a standard approach (group II; n = 33). A posterior-stabilized
      prosthesis was used in both groups by the same surgeon. Mean follow-up was 18
      months (range 14 - 26 months). Patients in group I lost less blood and
      experienced less pain 1 day post-operatively. They achieved an active straight
      leg raise earlier and underwent less lateral retinacular releases. Functional
      outcome and the range of knee movements were significantly better in group I up
      to 9 months post-operatively, but there was no significant difference between the
      groups at 1 year post-operatively or at final follow-up. Reduced access and
      visibility in group I prolonged the operation time and resulted in five technical
      errors on radiographic evaluation. Based on these results, the authors currently
      only use the mini-subvastus approach for minimally invasive TKA in selected
      cases.

PMID- 20819426
TI  - Non-invasive indices for the estimation of the anaerobic threshold of oarsmen.
AB  - This study compared four common non-invasive indices with an invasive index for
      determining the anaerobic threshold (AT) in 22 adult male rowers using a Concept2
      rowing ergometer. A criterion-standard progressive incremental test (invasive
      method) measured blood lactate concentrations to determine the 4 mmol/l threshold
      (La4-AT) and Dmax AT (Dm-AT). This was compared with three indices obtained by
      analysis of respiratory gases and one that was based on the heart rate (HR)
      deflection point (HRDP) all of which used the Conconi test (non-invasive
      methods). In the Conconi test, the HRDP was determined whilst continuously
      increasing the power output (PO) by 25 W/min and measuring respiratory gases and
      HR. The La4-AT and Dm-AT values differed slightly with respect to oxygen uptake,
      PO and HR however, AT values significantly correlated with each other and with
      the four non-invasive methods. In conclusion, the non-invasive indices were
      comparable with the invasive index and could, therefore, be used in the
      assessment of AT during rowing ergometer use. In this population of elite rowers,
      Conconi threshold (Con-AT), based on the measurement of HRDP tended to be the
      most adequate way of estimating AT for training regulation purposes.

PMID- 20819427
TI  - Hand-assisted laparoscopic surgery versus the open approach in curative resection
      of rectal cancer.
AB  - This prospective, randomized study compared the outcomes of hand-assisted
      laparoscopic surgery (HALS) with open surgery for the resection of rectal cancer.
      The main outcome measures were procedure time, blood loss, post-operative pain,
      time to oral intake, return of bowel function, length of hospital stay, morbidity
      and functional recovery. Patients in each group were similar with regard to
      general status, procedure types and the histopathological features of tumours.
      Procedure times were significantly longer with HALS versus open surgery.
      Analgesic requirements, surgical blood loss, time to first passing flatus, time
      to first oral fluids and post-operative hospital stay length were all
      significantly shorter in the HALS group. At a median follow-up of 16.3 months,
      local recurrence of tumour was not observed in either group. In this study, the
      HALS approach for curative resection of rectal cancer was safe and effective and
      may offer several potential advantages to patients in their post-operative
      recovery.

PMID- 20819428
TI  - Seminal plasma zinc level may be associated with the effect of cigarette smoking
      on sperm parameters.
AB  - The aim of this study was to investigate the effect of cigarette smoking on
      seminal plasma zinc levels and sperm parameters, and to examine the role of
      seminal plasma zinc. Semen samples from 79 non-smokers and 68 smokers were
      obtained. There was a significant decrease in seminal plasma zinc in smokers and
      a clear correlation between seminal plasma zinc levels and the extent of smoking.
      Sperm parameters (concentration, motility and morphology) among smokers were
      significantly lower in comparison to non-smokers. These parameters were also
      significantly decreased among smokers with abnormal zinc levels, while there was
      no significant difference between non-smokers with normal zinc and non-smokers
      with abnormal zinc levels. As previous studies have shown that seminal plasma
      zinc is associated with a decrease of anti-oxidant defences, seminal plasma zinc
      could be a contributor to the effects of cigarette smoking on sperm parameters.
      In conclusion, cigarette smoking can affect sperm parameters and this study may
      help towards providing a mechanistic explanation.

PMID- 20819429
TI  - Experimental study on angiogenesis in a rabbit VX2 early liver tumour by
      perfusion computed tomography.
AB  - Ten rabbits implanted with VX2 liver tumours were investigated by perfusion
      computed tomography (PCT) imaging 1 week (early) and 2 weeks (late) after tumour
      induction; 10 other rabbits were non-implanted controls. Time-density curves,
      perfusion parametric maps and perfusion parameters were obtained for tumour rim
      and normal tissue surrounding the tumour, and for liver tissue from the controls.
      In addition, microvessel density (MVD) and vascular endothelial growth factor
      (VEGF) were studied by immunohistochemistry 2 weeks after tumour implantation. A
      deconvolution mathematical model was used to calculate hepatic blood flow (HBF),
      hepatic blood volume (HBV), mean transit time (MTT), capillary vessel surface
      permeability (PS) and hepatic arterial index (HAI). At the tumour rim on the
      early PCT scan, MTT was significantly lower whereas HBF, HBV, HAI and PS were
      significantly higher than in surrounding normal tissue. There were no significant
      changes in perfusion parameters on the late PCT scan compared with the early
      scan. Significant linear correlations of MVD and VEGF were found with HBF, PS and
      HAI, but not with HBV or MTT. It is concluded that PCT imaging is useful for the
      evaluation of tumour angiogenesis and for the early detection of liver tumours.

PMID- 20819430
TI  - The beneficial effect of n-3 polyunsaturated fatty acids on doxorubicin-induced
      chronic heart failure in rats.
AB  - This study was designed to assess the effects of dietary supplementation with n-3
      polyunsaturated fatty acids (PUFA) from fish oil on the response of doxorubicin
      induced chronic heart failure in rats. Male Sprague-Dawley rats were treated
      daily for 8 weeks with normal saline or n-3 PUFA intragastrically after induction
      of myocardial injury by intraperitoneal injection of doxorubicin 2 mg/kg once
      weekly for 8 weeks. Cardiac function was assessed by echocardiography. The
      cytoprotective role of n-3 PUFA against doxorubicin-induced myocardial injury was
      demonstrated by light microscopy, and serum cytokines (tumour necrosis factor
      alpha and interleukin-10) were analysed by enzyme-linked immunosorbent assay.
      Doxorubicin induced death, alterations in echocardiography parameters and
      histological damage, all of which are features that characterize heart failure.
      There were significant differences between the doxorubicin-induced heart failure
      group and the n-3 PUFA-treated group in terms of echocardiography parameters and
      cytokine changes. Thus, dietary supplementation with n-3 PUFA attenuated
      doxorubicin-induced cardiac dysfunction, an effect that might be associated with
      recovery from an imbalance of the cytokine network.

PMID- 20819431
TI  - Expression of the genes encoding human leucocyte antigens-A, -B, -DP, -DQ and -G
      in gastric cancer patients.
AB  - This study compared the expression of the genes encoding human leucocyte antigens
      (HLA)-A, -B, -DP, -DR and -G in peripheral blood mononuclear cells (PBMCs) in
      gastric cancer patients and healthy controls. Using reverse transcription
      polymerase chain reaction, levels of classical HLA-A, -B, -DP and -DR and non
      classical HLA-G mRNA were studied in 43 gastric cancer patients and 22 controls.
      In addition, the levels of HLA-A,B,C and -G antigens on the surface of PBMCs were
      measured in 30 gastric cancer patients and 15 controls using flow cytometry. The
      mean fluorescence intensity of HLA-A,B,C antigen in the gastric cancer group was
      significantly lower than in controls. The HLA-G antigen was mainly present on
      CD4(+)CD8(-) T-lymphocytes. The percentage of CD4(+)CD8(-) T-lymphocytes positive
      for HLA-G antigen was significantly lower in the gastric cancer group compared
      with the healthy controls. Levels of HLA-A, -B and -G mRNA in the gastric cancer
      group were significantly lower than in controls. The HLA-G mRNA levels were
      significantly lower in gastric cancer of histological grades III and IV than in
      grades I and II. These data may provide a novel diagnostic and research tool for
      gastric cancer.

PMID- 20819432
TI  - A comparative study of transfection efficiency between liposomes, immunoliposomes
      and brain-specific immunoliposomes.
AB  - This study investigated the transfection ability and efficiency of liposomes and
      immunoliposomes for exogenous gene delivery into the brain via the venous system.
      Four groups of rats underwent tail vein injection with one of the following:
      liposomes encapsulating pCMV (human cytomegalovirus promoter)-LacZ plasmid 80
      microg (low dose) or 300 microg (high dose); general immunoliposomes
      encapsulating 80 microg transferrin receptor antibodies (OX26)-pCMV-LacZ plasmid;
      or brain-specific immunoliposomes encapsulating 80 microg OX26-pGFAP (glial
      fibrillary acidic protein promoter)-LacZ plasmid. A control group received no
      injected agent. The LacZ mRNA levels (1 h post-injection) and beta-galactosidase
      activity (48 h post-injection) in the brain and peripheral organs were assayed
      using real-time reverse transcription-polymerase chain reaction and histochemical
      staining, respectively. Both immunoliposomes delivered exogenous DNA containing
      the LacZ gene into the brain after venous injection, resulting in extensive LacZ
      expression in the brain. Furthermore, the brain-specific OX26-pGFAP-LacZ
      immunoliposome decreased the non-specific expression of LacZ in peripheral organs
      without affecting transfection efficiency in the brain. Thus, brain-specific
      immunoliposomes are an efficient and brain-specific targeting vector.

PMID- 20819433
TI  - Effects of ulinastatin and cyclophosphamide on the growth of xenograft breast
      cancer and expression of CXC chemokine receptor 4 and matrix metalloproteinase-9
      in cancers.
AB  - The aim of this study was to evaluate the effects of ulinastatin (UTI) and
      cyclophosphamide (CTX) as mono therapies and as combination therapy on the growth
      of mouse xenograft breast tumours. MCF-7 breast cancer cells were xenografted
      into 48 nu/nu nude mice in order to construct a breast cancer xenograft nude
      mouse model; mice were then untreated (control), or treated with CTX 0.1 g/kg
      every other day, UTI once a day at 25 000 U (low), 50 000 U (medium) or 100 000 U
      (high), or CTX + UTI (low), CTX + UTI (medium) or CTX + UTI (high) (n = 6
      mice/group). Compared with controls, mice in each drug-treated group had a
      significantly reduced tumour weight, and protein and mRNA levels of CXC chemokine
      receptor 4 and matrix metalloproteinase-9 in both the UTI (low, medium and high
      doses) and CTX groups were significantly reduced, while levels in the UTI (low,
      medium and high doses) + CTX combination groups were significantly reduced
      compared with the CTX group and the UTI (low, medium, high) groups. Thus, both
      UTI and CTX can significantly inhibit xenograft tumours, and the UTI + CTX
      combination exhibited an additive effect that was superior to both CTX and UTI
      monotherapy.

PMID- 20819434
TI  - Genetic polymorphisms of cytochrome P450 and glutathione S-transferase associated
      with antituberculosis drug-induced hepatotoxicity in Chinese tuberculosis
      patients.
AB  - This study was designed to investigate the association of genetic polymorphisms
      of cytochrome P450 subtype 2E1 (CYP2E1) and glutathione S-transferase mu 1
      (GSTM1) with susceptibility to antituberculosis drug-induced hepatotoxicity
      (ADIH) in Chinese tuberculosis patients. All patients were treated with a
      combination of isoniazid, rifampicin, pyrazinamide and ethambutol. Genomic DNA
      from 104 patients with ADIH and 111 without ADIH was analysed for the frequency
      of CYP2E1 RsaI and GSTM1 RsaI genotypes by polymerase chain reaction and
      restriction fragment length polymorphism. The association of polymorphisms with
      susceptibility to ADIH was calculated using the chi(2)-test and logistic
      regression analysis. The CYP2E1 RsaI polymorphisms were significantly associated
      with ADIH and the c1/c1 genotype was an independent risk factor for ADIH.
      Compared with the GSTM1 RsaI present genotype, the GSTM1 RsaI null genotype
      tended to increase susceptibility to ADIH, but the association with ADIH was not
      significant. The results indicate that CYP2E1 RsaI genotype c1/c1 is a potential
      risk factor for ADIH in the Chinese population. The tendency of the GSTM1 RsaI
      null genotype to increase susceptibility to ADIH needs further study.

PMID- 20819435
TI  - Differences in mitochondrial proteins in the eutopic endometrium of patients with
      adenomyosis and endometriosis identified using surface-enhanced laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - Adenomyosis and endometriosis have a similar pathogenesis; indeed, adenomyosis
      has been considered by some as a variant of endometriosis ('internal
      endometriosis'). This study aimed to detect differences in mitochondrial proteins
      in eutopic endometrial samples from women with adenomyosis (n = 13) and
      endometriosis (n = 24), and from control patients (n = 29) using surface-enhanced
      laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS)
      protein chip technology. A total of 82 and 78 mitochondrial protein peaks were
      found in adenomyosis and endometriosis individuals, respectively. Of these, 14
      were common to women with adenomyosis and women with endometriosis, although only
      one of these (mass-to-charge [m/z] ratio 3499) was significantly different
      between the adenomyosis and endometriosis groups. It is concluded that, compared
      with control patients, there are differences in the mitochondrial proteins
      isolated from the eutopic endometrium of patients with adenomyosis and those with
      endometriosis. Although the changes in mitochondrial proteins in eutopic
      endometrium from patients with adenomyosis and endometriosis were largely
      similar, significant differences were also detected. Further identification of
      these proteins and elucidation of the differences will help towards the
      differential diagnosis of adenomyosis and endometriosis and new therapeutic
      approaches.

PMID- 20819436
TI  - Growth suppression of human laryngeal squamous cell carcinoma by adenoviral
      mediated interleukin-12.
AB  - This study explored the inhibitory role of the adenoviral-mediated-interleukin
      (IL)-12 (Ad.mIL-12) gene in the growth of laryngeal squamous cell carcinoma
      (LSCC). Human epithelial type 2 (Hep-2) cells were transfected with Ad.mIL-12,
      and IL-12 gene expression of the cells was evaluated. The proliferation and
      apoptosis of Hep-2 cells in vitro were detected by MTT (3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry. Experimental
      tumours in mice were injected intratumourally with the same recombinant
      adenoviruses and inhibition of tumour growth observed. Apoptosis in Hep-2
      xenotransplants was detected using TUNEL (terminal deoxynucleotidyl transferase
      dUTP nick-end labelling) assay and transmission electron microscopy. The
      expression of IL-12 in Ad.mIL-12 transfected Hep-2 cells was significantly
      increased. In vitro, Ad.mIL-12 decreased the viability of and increased apoptosis
      in Hep-2 cells. Increased apoptosis was also seen in vivo. The mean weight and
      volume of tumours in Ad.mIL-12 treated mice were significantly lower than in the
      control group. It is concluded that Ad.mIL-12 can suppress LSCC growth and induce
      apoptosis.

PMID- 20819437
TI  - Experimental research on wild-type p53 plasmid transfected into retinoblastoma
      cells and tissues using an ultrasound microbubble intensifier.
AB  - The transfection efficiency of wild-type p53 (wtp53) was investigated in
      retinoblastoma (RB) Y79 cells using an ultrasound microbubble technique. A human
      RB nude mouse xenograft tumour model was also used to investigate whether this
      technique could deliver wtp53 into solid tumours. Reverse transcription
      polymerase chain reaction (RT-PCR) demonstrated that wtp53 was successfully
      transfected into Y79 cells in the plasmid with microbubbles and ultrasound group
      and in the plasmid with liposomes group, but not in the plasmid with ultrasound
      group or in the untreated control group. Flow cytometry showed that apoptosis was
      highest in the microbubbles and ultrasound group (25.58%) compared with the
      plasmid with liposomes group (19.50%), and the other two groups (< 10%). RT-PCR
      also showed that the wtp53 gene was successfully transfected into solid tumours
      in the plasmid with microbubbles and ultrasound group. This study provides
      preliminary evidence in support of a potential new approach to RB gene therapy.

PMID- 20819438
TI  - Decreased chaperone activity of alpha-crystallins in naphthalene-induced cataract
      possibly results from C-terminal truncation.
AB  - Naphthalene-induced cataract has been extensively used to test potential
      anticataract drugs. Because the morphology as well as the toxic manifestations of
      naphthalene-induced cataract are reported to be similar to that of age-related
      cataract, naphthalene cataractogenesis in rats has been used as a valuable animal
      model to study the aetiology of age-related cataract in humans. This study aimed
      to determine whether the molecular chaperone activity of the alpha-crystallins
      was altered in naphthalene-induced cataract, and to clarify the possible
      mechanism for these changes. The data showed that the chaperone activity of the
      alpha-crystallins decreased in naphthalene-induced cataract. By mass
      spectrometry, C-terminal truncation of 16 amino acids and other post
      translational modifications such as acetylation, phosphorylation, oxidation and
      carbamylation of the alpha-crystallins were detected. Furthermore, the results
      suggested that, at the proteomics level, naphthalene-induced cataract is a
      valuable animal model for the study of age-related cataract in humans.

PMID- 20819439
TI  - Effect of gentamicin-absorbed collagen in wound healing in pilonidal sinus
      surgery: a prospective randomized study.
AB  - Pilonidal sinus is a common disease that causes the loss of many working hours,
      but treatment is variable and problematic. The effect of gentamicin-absorbed
      collagen on healing, infection and recurrence, and length of hospital stay were
      examined after pilonidal sinus surgery. Patients undergoing surgical treatment
      for pilonidal sinus were randomly assigned into two groups each of 40 patients.
      Both groups were treated with excision and primary closure under local
      anaesthesia. Group 1 (control) received oral antibiotics for 7 days post
      operatively. In group 2, prior to wound closure, gentamicin-absorbed collagen
      sponges were placed on the sacral fascia and these patients did not receive oral
      post-operative antibiotic therapy. Patients in group 2 had a significantly
      shorter mean wound healing time, significantly lower infection and recurrence
      rates, and a significantly shorter hospital stay than those in group 1. It is
      concluded that implantation of a gentamicin-containing collagen sponge on the
      wound area in pilonidal sinus decreased the rates of infection and recurrence,
      and shortened the hospital stay.

PMID- 20819440
TI  - Documentation of post-operative nausea and vomiting in routine clinical practice.
AB  - This study investigated the quality of documentation of post-operative nausea and
      vomiting (PONV) by comparing incidences collected by a research team with those
      reported routinely by nursing personnel. A total of 560 patients passing through
      an interdisciplinary recovery room were included in the study. The overall
      recorded incidence of PONV over 24 h was 30.7%, which was in agreement with the
      predicted value of 32% calculated using incidences from published randomized
      controlled trials. Out of the total number of 86 cases of PONV in the recovery
      room only 36 (42%) were detected by nursing staff. Similarly, out of the total
      number of 129 cases of PONV on the ward over 24 h, only 37 (29%) were recognized
      by nursing staff during routine care. In conclusion, PONV in routine clinical
      care is likely to be under-reported. To use PONV as a valid quality measure,
      patients need to be actively asked about nausea and vomiting at frequent
      intervals in a standardized fashion. A considerable proportion of patients
      experience PONV after discharge from the recovery room, so the assessment of PONV
      should cover at least 24 h post-operatively.

PMID- 20819441
TI  - Expression of the actin-binding proteins indicates that cofilin and fascin are
      related to breast tumour size.
AB  - This study was designed to investigate the expression of four actin-binding
      proteins, alpha-actinin-4, cofilin 1, fascin and elongation factor 1-alpha 2
      (eEF1A2), in samples of breast cancer from 112 patients with different stages of
      breast cancer (stages T0 - T1, T2 and T3) compared with normal control tissues (n
      = 33). Levels of eEF1A2 and alpha-actinin-4 mRNA appeared to be unrelated to
      tumour size, except for a significant down-regulation of alpha-actinin-4 mRNA in
      T3 cases. Significant up-regulation of cofilin 1 mRNA was associated with stages
      T0 - T1 and T2; up-regulation seen at stage T3 was not significant compared with
      control tissue. Fascin mRNA levels were significantly reduced at all three tumour
      stages (T0 - T1, T2 and T3) compared with control tissue. In conclusion, some
      components of the actin cytoskeletal system might hold significant potential as
      targets in future cancer therapies.

PMID- 20819442
TI  - CD8/MHC-I complex is specific but not sensitive for the diagnosis of
      polymyositis.
AB  - This study aimed to investigate immunostaining patterns for major
      histocompatibility complex class I (MHC-I) in different types of myopathies and
      to assess the diagnostic value of CD8/MHC-I complex for definite polymyositis.
      The study included 20 cases of definite polymyositis, 20 cases of dermatomyositis
      and 10 cases of dystrophies with muscle inflammation (inflammatory muscular
      dystrophy). Immunohistochemical staining with MHC-I antibody demonstrated the
      presence of MHC-I along the sarcolemma of scattered or small groups of non
      necrotic fibres in both polymyositis and inflammatory muscular dystrophy, whereas
      intense sarcolemmal immunostaining for MHC-I was diffusely present in almost all
      fibres in dermatomyositis. Double immunofluorescence labelling for CD8 and MHC-I
      detected the CD8/MHC-I complex in 20% of polymyositis cases with mononuclear cell
      infiltrates. No CD8/MHC-I complex was found in the dermatomyositis or
      inflammatory muscular dystrophy cases. The results suggest that MHC-I detection
      alone cannot be used as a reliable diagnostic test to differentiate polymyositis
      from dystrophies with secondary muscle inflammation. The CD8/MHC-I complex,
      although showing high specificity, is neither a sensitive nor an easy-to-handle
      diagnostic test for polymyositis.

PMID- 20819443
TI  - Changes in femoral head blood supply and vascular endothelial growth factor in
      rabbits with steroid-induced osteonecrosis.
AB  - The molecular aetiology of steroid-induced osteonecrosis (ON) is unclear. The aim
      of this study was to investigate changes in the femoral head blood supply and
      vascular endothelial growth factor (VEGF) protein levels following steroid
      induced ON of rabbit femoral heads in the early stage of the disease, and to
      investigate a possible mechanism for ON. Using a classic protocol, ON was induced
      in 30 male 28-week old New Zealand white rabbits. An additional 15 untreated
      rabbits served as controls. Change of blood supply in the proximal femur was
      assessed by dynamic magnetic resonance imaging and microangiography. The VEGF
      protein and mRNA levels were assessed by immunohistochemistry and quantitative
      real-time polymerase chain reaction, respectively. After 6 weeks, the results
      indicated that VEGF protein and mRNA levels were significantly lower and femoral
      head blood supply had also decreased significantly in ON(+) rabbits compared with
      controls. The down-regulation of VEGF may play a critical role in the disease
      process of ON.

PMID- 20819444
TI  - The diagnostic utility of maspin in the distinction between malignant
      mesothelioma and pulmonary adenocarcinoma.
AB  - Immunohistochemistry is frequently employed to differentiate between malignant
      mesothelioma (MM) and pulmonary adenocarcinoma (AC) infiltrating the pleura, but
      there is uncertainty as to which antibodies are most useful. The present study
      investigated the presence of the serine protease, maspin, in epithelioid MMs and
      evaluated the diagnostic utility of maspin for the differential diagnosis between
      epithelioid MM and pulmonary AC with pleural involvement. The results showed more
      frequent maspin immunostaining among AC cases compared with MM cases. Maspin
      positivity was significantly higher among AC cases with respect to both the
      extent and intensity of staining. A significant difference also existed between
      the two tumour types with respect to the overall maspin score. Despite these
      findings, the sensitivity and specificity of maspin positivity to detect AC were
      only 59% and 73%, respectively, indicating that detection of maspin is of no
      value for the differential diagnosis of AC and MM.

PMID- 20819445
TI  - Evaluation of the correlation between colour power Doppler flow imaging and
      vascular endothelial growth factor in breast cancer.
AB  - This study was designed to evaluate the correlation between blood flow, using
      colour power Doppler flow imaging [CPDI], and protein levels of vascular
      endothelial growth factor (VEGF), as measured by optical density (OD), in breast
      tumours. Breast cancer patients were observed pre-operatively using CPDI and VEGF
      protein levels were quantified by immunohistochemistry, and the correlation
      between the two was studied. The relationship between tumour angiogenesis and
      axillary lymph node (LN) metastasis was also analysed. Blood-flow grade was
      higher in the LN(+) group than in the LN(-) group; grade II - III blood flow was
      88.9% in the LN(+) group. The VEGF protein levels in the LN(+) group were also
      higher than in the LN(-) group. A significant positive correlation was observed
      between blood-flow grade and OD value for VEGF protein. Breast tumour
      angiogenesis was closely correlated with axillary LN metastasis. Higher blood
      flow was related to elevated VEGF protein levels and an increased risk of
      axillary node metastasis. CPDI could, therefore, indirectly demonstrate tumour
      angiogenesis before surgery, enabling planning of treatment and assessment of the
      prognosis.

PMID- 20819446
TI  - Neuroprotective effect of gypenosides against oxidative injury in the substantia
      nigra of a mouse model of Parkinson's disease.
AB  - Oxidative injury has been implicated in the aetiology of Parkinson's disease (PD)
      and gypenosides (GP), which are saponins with various bioactivities, have shown
      antioxidative effects in vitro. The present study was designed to evaluate the
      effect of GP on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced
      mouse model of PD. Acute administration of MPTP led to decreased glutathione
      content and reduced superoxide dismutase activity in the substantia nigra of the
      mice, which resulted in oxidative stress, loss of nigral dopaminergic neurons and
      motor dysfunction. Co-treatment with GP attenuated all the injuries induced by
      MPTP in a dose-dependent manner. The neuroprotective effect of GP may be
      attributed to increased antioxidation, as manifested by significantly increased
      glutathione content and enhanced superoxide dismutase activity in the substantia
      nigra. These results strongly indicate the possible therapeutic potential of GP
      as an antioxidant in PD.

PMID- 20819447
TI  - Association of vitamin D binding protein variants with susceptibility to chronic
      obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow
      limitation and it is thought that neutrophils play a major role in the disease
      pathogenesis. Genetic polymorphism of the vitamin-D-binding protein (VDBP) gene
      is considered one of the candidates for variation in susceptibility to COPD. To
      evaluate the potential influences of VDBP gene polymorphisms on COPD, a case
      control study was conducted in the Han population of north-east China. The VDBP
      polymorphic site was genotyped in 100 COPD patients and 100 controls. Genotypes
      were determined by polymerase chain reaction-restriction fragment length
      polymorphism. A significantly higher proportion of VDBP-1F homozygosity was found
      in COPD patients, while the frequency of VDBP-2 homozygosity was significantly
      lower in COPD patients, which seemed to suggest that VDBP-2 homozygocity provided
      a protective effect. These data suggest that the VDBP gene may be involved in
      COPD susceptibility in Chinese Han population.

PMID- 20819448
TI  - Clonal status and clinicopathological features of Langerhans cell histiocytosis.
AB  - Some studies have demonstrated that Langerhans cell histiocytosis (LCH) is a
      neoplastic hyperplasia of Langerhans cells, however some researchers consider
      that clonality should be assessed in more patients with LCH, both at disease
      presentation and during the disease course. Monoclonality is a major
      characteristic of most tumours, whereas normal tissue and reactive hyperplasia
      are polyclonal. To elucidate the nature of Langerhans cells further, the present
      study investigated the clinicopathological features and clonality of three cases
      of LCH in female patients using laser microdissection and a clonality assay,
      based on X-chromosomal inactivation mosaicism in somatic tissues and polymorphism
      of the androgen receptor gene. The results indicated that LCH was composed of
      Langerhans cells with a characteristic morphological appearance, eosinophils,
      giant cells, neutrophils and foamy cells. Immunohistochemically, the Langerhans
      cells were positive for CD1a, S-100 protein and vimentin. The clonality assay
      demonstrated that the Langerhans cells formed a monoclonal population, showing
      that LCH is neoplastic. We conclude that LCH is characterized by clonal
      proliferation, although additional studies with larger sample sizes are required
      to prove this conclusively.

PMID- 20819449
TI  - The influence of complete coronary revascularization on long-term outcomes in
      patients with multivessel coronary heart disease undergoing successful
      percutaneous coronary intervention.
AB  - The influence of complete revascularization (CR) compared with incomplete
      revascularization (ICR) on long-term outcomes was assessed in patients with
      multivessel coronary heart disease undergoing successful percutaneous coronary
      intervention (PCI). A retrospective analysis of the clinical data, lesion type
      and PCI data was carried out in 324 patients with multivessel coronary heart
      disease (CR group, 99 patients; ICR group, 225 patients). Major adverse cardiac
      events (MACE) were recorded at follow-up (mean +/- SD follow-up interval, 18 +/-
      7.1 months). There were no significant differences in clinical characteristics
      between the two groups at follow-up, although the CR group showed a non
      significant tendency to a higher incidence of non-fatal myocardial infarction,
      cardiac death, repeated revascularization and MACE compared with the ICR group.
      In conclusion, the long-term prognosis for ICR was not inferior to that for CR in
      patients with multivessel coronary heart disease undergoing successful PCI.

PMID- 20819450
TI  - Lentivirus-mediated gene transfer of small interfering RNA against the chemokine
      receptor CXCR3 suppresses cytokine indicators of acute graft rejection in a rat
      model.
AB  - Despite improvements in immunosuppressive therapy, acute rejection remains an
      important cause of morbidity and late graft loss in patients undergoing liver
      transplantation. Increasing evidence supports an important role for chemokines
      and their receptors in transplant immunology. An acute liver graft rejection
      model in rats was used to study the role of the chemokine receptor CXCR3 in acute
      transplant rejection after liver transplantation by lentivirus-mediated gene
      transfer of small interfering RNA (siRNA) against CXCR3. Using reverse
      transcription-polymerase chain reaction it was first shown that three lentivirus
      CXCR3 siRNA vectors inhibited the in vitro expression of CXCR3 in activated T
      cells bearing CXCR3. Then, it was shown that treatment of the animals with
      lentivirus-CXCR3 siRNA before liver transplantation reduced CXCR3 mRNA and
      protein, and protein levels of interleukin (IL)-2, IL-4, IL-6 and IL-10 and
      interferon-gamma measured as indices of acute graft rejection. Based on the
      results from this animal model, targeting chemokines by the use of siRNA may
      become a feasible option for therapy after transplantation.

PMID- 20819451
TI  - Transjugular intrahepatic portosystemic shunt versus endoscopic sclerotherapy in
      the elective treatment of recurrent variceal bleeding.
AB  - The present study was designed to compare elective transjugular intrahepatic
      portosystemic shunts (TIPS) and endoscopic sclerotherapy (EST) in terms of their
      efficacy in preventing recurrent bleeding from gastro-oesophageal varices in
      patients with advanced liver cirrhosis and portal hypertension. Of 96 patients
      with at least three gastro-oesophageal variceal rebleeds, 50 were treated with
      elective TIPS and 46 with EST. Recurrent variceal bleeding was significantly more
      frequent in patients receiving EST treatment compared with those receiving TIPS
      (45.7% versus 6.3%, respectively). Cumulative 1- and 4-year survival in the TIPS
      group was 83.0% and 73.5%, respectively, compared with 69.8% and 39.8% in the EST
      group, respectively. The rate of portosystemic encephalopathy was 33.3% in the
      TIPS group and 37.0% in the EST group. Elective TIPS was more effective than EST
      in the prevention of gastro-oesophageal variceal rebleeding in cirrhotic
      patients, it improved survival and it was associated with a similar rate of
      portosystemic encephalopathy.

PMID- 20819452
TI  - Clinical analysis of elderly patients with elderly-onset type 2 diabetes mellitus
      in China: assessment of appropriate therapy.
AB  - Patients with elderly-onset diabetes have specific characteristics. This study
      was designed to investigate these characteristics and to evaluate methods for
      appropriate control of glycaemia and cardiovascular risk factors in elderly-onset
      diabetes patients. A total of 155 elderly patients with type 2 diabetes mellitus
      were divided into those diagnosed at >or= 65 years of age (elderly-onset group,
      75 patients) and those diagnosed at < 60 years of age (usual-onset group, 80
      patients). Differences in clinical variables, diabetic complications, diagnosed
      comorbidities and the use of medications were analysed. Mean glycosylated
      haemoglobin, fasting plasma glucose and fasting insulin levels were significantly
      lower in the elderly-onset group than in the usual-onset group. The usual-onset
      group showed significantly greater homeostasis model assessment insulin
      resistance than the elderly-onset group. Microvascular complications and insulin
      use were significantly more common in the usual-onset group. In conclusion,
      insulin resistance was less severe in elderly-onset diabetes than in usual-onset
      diabetes. As hyperglycaemia was relatively mild or moderate, oral hypoglycaemic
      agents might be effective for elderly-onset diabetes.

PMID- 20819453
TI  - Metabolic syndrome: prevalence and risk factors in southern China.
AB  - This was a cross-sectional study to investigate the epidemiology of metabolic
      syndrome and the distribution of inter-related metabolic abnormalities in
      different population groups in Guangdong, southern China. Individuals were
      recruited according to the percentage of different occupational populations in
      southern China. The study cohort included 1206 subjects, and the prevalence and
      distribution of the components of metabolic syndrome were assessed using the
      National Cholesterol Education Program Adult Treatment Panel III 2005 criteria.
      The unadjusted rate of metabolic syndrome was 26.7%, and the prevalences of
      hypertension and diabetes were 38.0% and 4.3% respectively. Hypertension,
      diabetes, metabolic syndrome, abdominal obesity, elevated blood glucose and
      elevated blood pressure decreased significantly with increasing levels of life
      stress and anxiety. The prevalence of hypertension and metabolic syndrome in
      southern China is very high, and early identification and treatment of at-risk
      individuals may help target intervention to improve future cardiovascular health.

PMID- 20819454
TI  - Urodynamic study of bladder function for patients with lumbar spinal stenosis
      treated by surgical decompression.
AB  - Lumbar spinal stenosis usually leads to different degrees of nerve damage,
      presenting with back and leg pain, and/or neurogenic bladder symptoms. To
      determine whether lumbar decompression improved urological function, bladder
      dysfunction was evaluated in this retrospective study of 26 patients with lumbar
      spinal stenosis who had undergone lumbar decompression surgery. Urodynamic study
      procedures were performed pre-operatively and 6 months post-operatively. The
      Japanese Orthopaedic Association score rating system and Oswestry Disability
      Index were employed for clinical evaluation. Following surgery, post-voiding
      residual urine, maximum cystometric capacity and maximum flow rate improved
      significantly. There was no statistically significant improvement in voided
      volume, bladder compliance, maximum detrusor pressure or upper urinary tract
      damage. Urodynamic study was important in the diagnosis of neurogenic bladder
      dysfunction, prevention of renal deterioration and assessment of post-operative
      effects after surgical decompression for patients with lumbar spinal stenosis.

PMID- 20819455
TI  - Factors associated with multidrug-resistant tuberculosis: comparison of patients
      born inside and outside of the Czech Republic.
AB  - Multidrug-resistant tuberculosis (MDR-TB) is defined as resistance of
      Mycobacterium tuberculosis complex (MTB) to at least isoniazid and rifampicin.
      The aim of this study was to evaluate and compare a cohort of 50 patients with
      MDR-TB according to birthplace, resistance type, clinical outcome, length of
      bacteriological positivity of sputum and length of hospitalization. Thirty-three
      of the patients were born in the Czech Republic (group A) and 17 were immigrants
      to the Czech Republic (group B). Patients in group B were significantly younger
      (mean [range] age 33 [19 - 56] years) than those in group A (mean [range] age 48
      [33 - 80] years). Primary resistance was present in 16 (48%) cases in group A and
      in 13 (76%) cases in group B. There were 36 (72%) cured patients, five (10%)
      remained on treatment and nine (18%) died; no patients failed or transferred out
      of the study. The mean length of bacteriological positivity of sputum samples was
      5.9 months and the mean length of hospitalization was 8.2 months. Resistance to
      capreomycin was an important predictor of poor outcome.

PMID- 20819456
TI  - Malignant atrophic papulosis with severe gastrointestinal perforation and omental
      necrosis: a case report.
AB  - Malignant atrophic papulosis (MAP) is a rare disease with an extremely grim
      prognosis, death being due to gastrointestinal perforation and neurological
      disorders. We report a severe case of MAP in a 37-year old woman. The patient had
      three emergent laparotomies in 3 months for recurrent acute peritonitis due to
      omental thrombosis resulting in necrosis, multiple intestinal and mesenteric
      lesions, and severe gastrointestinal perforations. Multiple papular skin lesions
      were present for 1 year prior to surgery. Pathological findings revealed MAP.
      Surgical intervention was successful and the patient recovered smoothly but later
      died of malnutrition and septicaemia.

PMID- 20819457
TI  - CD20-positive T-cell lymphoma with indolent clinical behaviour.
AB  - T-cell lymphomas that are positive for CD20 are very rare and most reported cases
      have demonstrated an aggressive clinical course. An unusual case of a 57-year old
      female who presented with recurrent enlarged lymph nodes for 12 years is
      reported. The lymph nodes from both 1995 and 2007 showed effacement of the lymph
      node architecture by a diffuse and dense infiltrate of small lymphoid cells. In
      terms of T- and B-cell markers, these small lymphoid cells were
      immunohistochemically positive for CD2, CD3, CD5, CD43, CD45RO and CD20, and were
      negative for PAX5, CD79a and cyclin D1. Molecular genetic analysis showed T-cell
      receptor-gamma chain gene rearrangement. Recognition of this type of CD20
      positive T-cell lymphoma is important for ensuring a correct diagnosis so that
      the patient can be offered the most appropriate therapy. The indolent behaviour
      of the present case is unusual and awaits further clinical follow-up and
      laboratory investigation.

PMID- 20819459
TI  - Clinical characteristics and therapeutic outcomes of patients with localized
      mucosal allergy.
AB  - BACKGROUND: Many researchers have focused on the definition and pathophysiology
      of localized mucosal allergy. However, there are few studies on its clinical
      characteristics and therapeutic outcomes. The goal of this study was to analyze
      the prevalence, epidemiology, clinical characteristics, and response to
      antiallergic medication of localized mucosal allergy patients compared with those
      in patients with allergic rhinitis. METHODS: Among 836 patients suspected to have
      rhinitis, 29 patients with localized mucosal allergy (group A) and 29 patients
      with allergic rhinitis (group B) were selected. Medical history, family history,
      symptoms, and their severity were obtained using a questionnaire. The change in
      minimal cross-sectional area (MCA) after provocation was measured by acoustic
      rhinometry. After 2 weeks of antihistamine medication, the changes in symptoms
      were compared between groups. RESULTS: The prevalence of localized mucosal
      allergy was approximately 3.5%. There were no differences in patient history,
      symptoms, or symptom severity. The decrease in MCA after provocation was not
      significantly different. After two weeks of oral antihistamine (ebastine 10 mg
      once daily), group A reported significantly less symptom improvement than group
      B. CONCLUSION: Because patient or family history and clinical picture are very
      similar in localized mucosal allergy and allergic rhinitis, clinicians should
      take more care in differentiating them. Based on the reduced effectiveness of an
      oral antihistamine alone, a combined regimen of oral and topical antihistamine or
      anti-inflammatory medication is recommended for patients with localized mucosal
      allergy.

PMID- 20819460
TI  - Allergic rhinitis and inflammatory airway disease: interactions within the
      unified airspace.
AB  - BACKGROUND: Allergic rhinitis (AR), the most common chronic allergic condition in
      outpatient medicine, is associated with immense health care costs and
      socioeconomic consequences. AR's impact may be partly from interacting of
      respiratory conditions via allergic inflammation. This study was designed to
      review potential interactive mechanisms of AR and associated conditions and
      consider the relevance of a bidirectional "unified airway" respiratory
      inflammation model on diagnosis and treatment of inflammatory airway disease.
      METHODS: MEDLINE was searched for pathophysiology and pathophysiological and
      epidemiologic links between AR and diseases of the sinuses, lungs, middle ear,
      and nasopharynx. RESULTS: Allergic-related inflammatory responses or neural and
      systemic processes fostering inflammatory changes distant from initial allergen
      provocation may link AR and comorbidities. Treating AR may benefit associated
      respiratory tract comorbidities. Besides improving AR outcomes, treatment
      inhibiting eosinophil recruitment and migration, normalizing cytokine profiles,
      and reducing asthma-associated health care use in atopic subjects would likely
      ameliorate other upper airway diseases such as acute rhinosinusitis, chronic
      rhinosinusitis (CRS) with nasal polyposis (NP), adenoidal hypertrophy, and otitis
      media with effusion. CONCLUSION: Epidemiological concordance of AR with several
      airway diseases conforms to a bidirectional "unified airway" respiratory
      inflammation model based on anatomic and histological upper and lower airway
      connections. Epidemiology and current understanding of inflammatory, humoral, and
      neural processes make links between AR and disorders including asthma, otitis
      media, NP, and CRS plausible. Combining AR with associated conditions increases
      disease burden; worsened associated illness may accompany worsened AR. AR
      pharmacotherapies include antihistamines, leukotriene antagonists, intranasal
      corticosteroids, and immunotherapy; treatments attenuating proinflammatory
      responses may also benefit associated conditions.

PMID- 20819461
TI  - Gastroesophageal reflux disease and chronic sinusitis: in search of an esophageal
      nasal reflex.
AB  - BACKGROUND: This study was performed to explore whether or not a neural reflex
      linking the esophagus and the nasal airway exists, as a pathogenic mechanism
      accounting for the association between gastroesophageal reflux (GER) disease and
      chronic rhinosinusitis (CRS). A prospective trial of healthy human volunteers was
      performed. METHODS: Ten healthy volunteers without GER or sinonasal disease were
      investigated using an acid infusion challenge test. Normal saline and
      hydrochloric acid were infused into the lower esophagus through an esophageal
      manometry catheter. Nasal responses in symptom score, nasal inspiratory peak
      flow, and mucus production were analyzed after the esophageal challenge. RESULTS:
      A tendency for an increase in nasal mucus production was observed after
      esophageal stimulation with both normal saline and HCl. This returned to baseline
      level 45 minutes after the acid infusion. A similar trend was also observed with
      the measurements of nasal symptom scores and, to a lesser extent, nasal
      inspiratory peak flow. CONCLUSION: These results support the possibility that a
      neural reflex exists between the esophagus and the paranasal sinuses via the
      vagus nerve. If indeed present, the reflex-mediated rhinitis derived from this
      neuropathic inflammation may contribute to the development of CRS in patients
      with GER. Further study is required to define the relationship between GER and
      CRS.

PMID- 20819462
TI  - Use of cold dry air provocation with acoustic rhinometry in detecting nonspecific
      nasal hyperreactivity.
AB  - BACKGROUND: Cold dry air provocation is useful for evaluating nonspecific nasal
      hyperreactivity. However, there is no research on nasal volume and dimensions
      after cold dry air provocation. In this respect, acoustic rhinometry is a useful
      tool in objectively assessing nasal cavity volume and dimension. The goal of this
      study was to evaluate nonspecific hyperreactivity using cold dry air provocation
      with acoustic rhinometry. METHODS: Cold dry air provocation with acoustic
      rhinometry was performed on 21 healthy volunteers (group A), 24 patients with
      allergic rhinitis (group B), and 32 patients with nonallergic rhinitis (group C).
      The change in symptoms using a visual analog scale (VAS), amount of rhinorrhea,
      and change of total nasal volume (TNV) and minimal cross-sectional area (MCA)
      were measured in all three groups. RESULTS: The two patient groups showed greater
      change in nasal symptoms (VAS, 2.0 +/- 2.3 in group C versus 0.9 +/- 1.8 in group
      A), more rhinorrhea (0.4 +/- 0.7 g in group B and 0.3 +/- 0.3 g in group C versus
      0.1 +/- 0.1 g in group A), and greater change in total nasal volume (TNV) and
      MCA. The patient group with history of nonspecific hyperreactivity showed more
      rhinorrhea (0.5 +/- 0.7 g versus 0.1 +/- 0.2 g) and greater change in TNV and MCA
      (TNV, 56.8 +/- 39.5% versus 18.0 +/- 17.0%; MCA, 86.6 +/- 81.0% versus 11.5 +/-
      9.7%). CONCLUSION: Cold dry air provocation with acoustic rhinometry could be a
      useful adjunct tool for detecting nonspecific hyperreactivity.

PMID- 20819463
TI  - Nucleic acid extraction efficiency and bacterial recovery from maxillary sinus
      mucosal samples obtained by brushing or biopsy.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is a common disease with a complex
      pathophysiology involving a microbial component. Culture-independent molecular
      analysis represents a promising new approach to clarify the microbiology of CRS,
      but standardized, optimized sampling methods still have not been defined. This
      study was designed to compare nucleic acid extraction rates and recovery of
      bacteria for two methods of sampling the maxillary sinus, mucosal biopsy, and
      brushing. METHODS: Samples were obtained from 20 patients undergoing maxillary
      sinus surgery. Total extracted nucleic acid concentration and bacterial burden
      were compared between sample types. RESULTS: Total nucleic acid concentration
      varied across patients. No statistically significant difference in mean total DNA
      concentration from mucosal biopsy specimens or brushings was observed. However,
      compared with biopsy specimens, brush samples possessed a significant (p < 0.035)
      increase in bacterial copy number. CONCLUSION: Endoscopically directed mucosal
      brushings of the maxillary sinus provide equivalent concentrations of total DNA
      to mucosal biopsy specimens but possess greater concentrations of bacterial DNA,
      likely because of the greater surface area sampled by this method. Given the
      additional advantage of lower risk associated with obtaining brush samples, we
      suggest they represent the preferred sampling method for future genomic sinus
      studies.

PMID- 20819464
TI  - The role of hepatocyte growth factor/c-Met in chronic rhinosinusitis with nasal
      polyps.
AB  - BACKGROUND: Hepatocyte growth factor (HGF) is a growth factor thought to
      attenuate Th2-driven eosinophilic airway inflammatory responses. Increased
      expression of HGF and its receptor c-Met in nasal polyps suggests a role in
      disease pathogenesis. The effect of HGF on human sinonasal epithelial cell (SNEC)
      responses to Th2 inflammatory cytokines in chronic rhinosinusitis with nasal
      polyps (CRSwNP) has not been explored. METHODS: SNECs isolated from patients with
      CRSwNP and control subjects were grown in cell culture at the air-liquid
      interface. The Th2 cytokine IL-13 was applied for 24 hours in the presence or
      absence of HGF. Eotaxin-3 and c-Met expression was assessed using real-time PCR,
      immunohistochemistry, and flow cytometry. RESULTS: SNECs obtained from both
      CRSwNP and control subjects showed markedly increased expression of eotaxin-3
      after exposure to IL-13. HGF significantly blocked IL-13-induced expression of
      eotaxin-3 in control SNECs, but not in SNECs derived from CRSwNP subjects.
      CONCLUSION: SNECs are active participants in sinonasal mucosal immunity,
      expressing inflammatory mediators in response to potential pathogens and
      endogenous cytokines. Although Th2 cytokines can elicit expression of
      proeosinophilic mediators by SNECs, HGF appears to have a down-regulating effect
      on this response. In patients with CRSwNP, SNECs are resistant to this
      attenuation, showing continued IL-13-induced eotaxin-3 expression despite HGF
      treatment. Abnormalities in the regulation of epithelial cell responses to
      endogenous cytokines and growth factors may contribute to the persistent
      eosinophilic inflammatory state in CRSwNP.

PMID- 20819465
TI  - Clinical and immunologic effects of sublingual immunotherapy on patients with
      allergic rhinitis to house-dust mites: 1-year follow-up results.
AB  - BACKGROUND: There have been no data on sublingual immunotherapy (SLIT) in Asian
      patients with allergic rhinitis (AR) sensitized to house-dust mites (HDMs). This
      study aimed to investigate the efficacy and immunologic change after 12 months of
      SLIT in Korean patients. METHODS: Fifty-eight patients, who had AR caused by
      Dermatophagoides pteronyssinus and Dermatophagoides farinae and who completed 12
      months of SLIT were included. Symptom scores were evaluated before and after 12
      months of SLIT, and medication scores were assessed throughout the study.
      Peripheral blood eosinophil counts, eosinophil cationic protein (ECP), total IgE,
      and specific IgE were also evaluated. RESULTS: All of the symptoms of AR were
      significantly improved with reduced medication scores. In addition, there were
      significant decrements in peripheral blood eosinophil counts and ECP (p = 0.025
      and p = 0.048, respectively). Specific IgE for D. farinae slightly increased (p =
      0.019), whereas specific IgE for D. pteronyssinus and total IgE did not change
      significantly. Thirty-six (62%) of 58 patients were in the effective response
      group. Although not statistically significant, findings in the study showed that
      the effective response group had a tendency to have higher ECP levels before SLIT
      than the ineffective response group (p = 0.056). CONCLUSION: SLIT improved the
      symptoms and medication scores in Korean patients with AR from HDM. Laboratory
      parameters including eosinophil counts, ECP, and specific IgE for D. farinae
      seemed to be modified after 1-year SLIT. A high ECP level may be a useful
      parameter to predict the effectiveness of SLIT and select the patient for the
      treatment.

PMID- 20819466
TI  - Biometric predictive models for the evaluation of olfactory recovery after
      endoscopic sinus surgery in patients with nasal polyposis.
AB  - BACKGROUND: Determination of predictive factors and specific values of olfactory
      function after endoscopic sinus surgery (ESS) using objective diagnostic methods
      may support consultation of respective patients. This study was designed to
      assess the longitudinal olfactory functional outcome after ESS in patients with
      severe chronic rhinosinusitis (CRS) with nasal polyposis, to evaluate associated
      clinical factors and to provide statistical models for prediction of olfactory
      recovery. METHODS: One hundred sixteen patients with nasal polyposis refractory
      to medical treatment underwent ESS. Olfactory testing was performed
      preoperatively and 1, 3, and 6 months after surgery using "Sniffin' Sticks"
      (Burghardt, Wedel, Germany). Using multivariate linear and logistic regression
      analysis, statistical models were generated to predict (i) the 6th-month
      composite threshold-discrimination-identification (TDI) score and (ii) the
      probability of attaining normal olfaction at 6 months. RESULTS: A significant
      stepwise increment of all olfactory function indices was found over time. Factors
      influencing final olfactory recovery were patients' age, duration of olfactory
      deficit, previous paranasal sinus surgery, and aspirin-exacerbated respiratory
      disease. The first model explained 70% of the observed variation in postoperative
      TDI scores. The second model correctly classified 76% of the patients.
      CONCLUSION: A significant progressive improvement of olfaction for at least 6
      months was observed after ESS. The statistical models developed may be useful for
      consultation of ESS candidates in clinical practice.

PMID- 20819467
TI  - Ethmoid histopathology does not predict olfactory outcomes after endoscopic sinus
      surgery.
AB  - BACKGROUND: Histological inflammation correlates with the degree of baseline
      olfactory dysfunction in patients with chronic rhinosinusitis (CRS); however,
      factors associated with improvement in olfactory status after endoscopic sinus
      surgery (ESS) remain elusive. Our purpose was to compare histopathological
      findings in CRS patients with olfactory loss and evaluate whether inflammatory
      markers can predict long-term olfactory improvement after ESS. METHODS: Adult (>
      or = 18 years) patients with CRS were prospectively enrolled after electing ESS
      due to failed medical management. Mucosal tissue specimens were collected at the
      time of surgery and underwent pathological review in a blinded fashion. Subjects
      completed the 40-item Smell Identification Test (SIT) preoperatively and at least
      6 months postoperatively. Multivariate logistic regression was used to identify
      histological factors associated with postoperative improvement in SIT score.
      RESULTS: The final cohort was comprised of 101 patients with a mean follow-up of
      16.7 +/- 6.0 months. Mean mucosal eosinophil count was higher in patients with
      hyposmia and anosmia (p < 0.001). Patients with preoperative anosmia were more
      likely to have greater severity of basement membrane (BM) thickening compared
      with subjects with hyposmia or normosmia (p = 0.021). In patients with olfactory
      dysfunction, 54.7% reported olfactory improvement of at least 4 points on
      postoperative SIT scores. After controlling for nasal polyposis, histological
      variables were not associated with postoperative improvement in olfaction.
      CONCLUSION: Patients with severe olfactory dysfunction were more likely to have
      mucosal eosinophilia and BM thickening on ethmoid histopathological examination
      compared with normosmic patients. The presence of specific histological
      inflammatory findings did not, however, predict olfactory improvement after
      surgery.

PMID- 20819468
TI  - Olfactory cleft inflammation is present in seasonal allergic rhinitis and is
      reduced with intranasal steroids.
AB  - BACKGROUND: Allergic rhinitis (AR) is commonly associated with olfactory loss,
      although the mechanism is not well studied. This study was designed to determine
      the effect of mometasone furoate (MF) on olfactory loss in seasonal AR (SAR) and
      study its effect on inflammation in the olfactory region. METHODS: We performed a
      randomized, double-blind, placebo-controlled, parallel clinical trial in 17
      patients with SAR who had symptoms of impaired olfaction. Subjects received MF or
      placebo for 2 weeks during their allergy season. Before and after treatment, we
      measured nasal peak inspiratory flow (NPIF), chemosensory quality of life, and
      objective olfactory function (the University of Pennsylvania Smell Identification
      Test). Additionally, nasal cytology samples were obtained from each visit, and a
      unilateral endoscopic biopsy specimen of the olfactory epithelium was obtained at
      the end of the study and scored for inflammation. RESULTS: Treatment with MF was
      associated with improved nasal symptoms (p < 0.015), NPIF (p < 0.04), reduced
      nasal inflammation (p < 0.05), and chemosensory-specific quality of life (p <
      0.03). Histological analysis of the olfactory region reveals fewer eosinophils in
      the MF group when compared with placebo (p < 0.012). We found no improvement in
      objective olfactory function (p > 0.05). CONCLUSION: The use of MF in SAR is
      associated with reduced eosinophilic inflammation in the olfactory region and
      improved symptoms of AR. The presence of eosinophils in the olfactory area in SAR
      may indicate a direct, deleterious effect of inflammation on olfactory epithelium
      in this disease. In this study we show that inflammation in SAR can affect the
      olfactory cleft, implicating a direct role for allergic inflammation in smell
      loss. Treatment with intranasal steroids is associated with decreased
      inflammation in the olfactory region in humans. This treatment is also associated
      with improved olfactory quality of life.

PMID- 20819469
TI  - Unrecognized odontogenic maxillary sinusitis: a cause of endoscopic sinus surgery
      failure.
AB  - BACKGROUND: Endoscopic sinus surgery (ESS) is reported to improve symptoms in
      approximately 85% of patients. Reasons for failure include misdiagnosis,
      technical inadequacies, underlying severe hyperplastic disease, biofilm, and
      immunodeficiency. Only one previous case of unrecognized odontogenic maxillary
      sinusitis has been cited in the literature as a reason for failure to improve
      with sinus surgery. This study was designed to characterize clinical and
      radiographic findings in patients who fail to improve with ESS because of an
      unrecognized dental etiology. METHODS: Five patients, with odontogenic maxillary
      sinusitis with prior unsuccessful ESS, were prospectively enrolled. Demographics
      and clinical aspects including duration of illness, prior sinus surgeries and
      therapies, and radiographic data were assessed. RESULTS: Five adults underwent an
      average of 2.8 sinus surgeries with persistence of disease and symptoms until
      their dental infection was treated. Duration of symptoms ranged from 3 to 15
      years. In four of five patients, the periapical abscess was not noted on the
      original CT report but could be seen in retrospect. Three of five patients had
      been seen by their dentists and told they had no dental pathology. All five
      patients underwent dental extractions and one patient underwent an additional ESS
      after dental extraction. These procedures led to a resolution of sinusitis
      symptoms in all five patients. CONCLUSION: Unrecognized periapical abscess is a
      cause of ESS failure and the radiological report frequently will fail to note the
      periapical infection. Dentists are unable to recognize periapical abscesses
      reliably with dental x-rays and exam. In patients with maxillary sinus disease,
      the teeth should be specifically examined as part of the radiological workup.

PMID- 20819470
TI  - Using fixed anatomical landmarks in endoscopic skull base surgery.
AB  - BACKGROUND: The identification of anatomic landmarks in endoscopic skull base or
      revision sinus surgery can be challenging. Normal anatomy is significantly
      altered with many paranasal tumors. Traditional endoscopic surgical landmarks
      extrapolated from inflammatory disease, such as the superior turbinate, may have
      been previously removed or involved in pathology. A frequently used rule to enter
      the sphenoid, "stay below or at the level of the orbital floor as dissection
      proceeds posteriorly and one will avoid the skull base," is assessed
      anatomically. METHODS: The maxillary sinus roof height, relative to the nasal
      floor, was assessed as an operative landmark. Computed tomography (CT) performed
      on paranasal sinuses was studied. The relative height, ratio, and proportions of
      the maxillary sinus, ethmoid roof, cribriform fossa, and sphenoid planum were
      measured using computerized assessments. RESULTS: Three hundred paranasal sinus
      systems were evaluated. The roof of the maxillary sinus was below the level of
      the skull base in 100% relative to the cribriform and 100% relative to the
      sphenoid planum. The mean distance of the maxillary roof below the skull base was
      10.1 +/- 2.7 mm for the cribriform and 11.0 +/- 2.9 mm for the sphenoid.
      CONCLUSION: The maxillary sinus roof can be used as a robust landmark to allow
      safe dissection and debulking of pathology. Pathology removal can proceed
      posterior with this landmark to enable a safe entry to the sphenoid sinus, and
      thus the true skull base, when normal structures such as the superior turbinate
      and ostium are not available.

PMID- 20819471
TI  - Prophylactic antibiotics in endoscopic sinus surgery: a short follow-up study.
AB  - BACKGROUND: The study was designed to assess the usefulness of postoperative
      antibiotics in patients undergoing endoscopic sinus surgery (ESS). METHODS: The
      effects of antibiotics in the postoperative period of ESS patients were evaluated
      in a prospective, randomized, double-blind, placebo-controlled study. Fifty
      patients were treated with amoxicillin/clavulanate for 2 weeks after ESS, while
      the other half received placebo. Preoperatively, the symptom, endoscopic, and CT
      scores were recorded. In the postoperative period, symptom and endoscopic scores
      were recorded on the 5th, 12th, 21st, and 30th days. In estimating the length of
      the blood crust formation episode, a Kaplan-Meier plot was used. RESULTS: Seventy
      five patients completed the study: forty in the antibiotic-treated group and
      thirty-five in the placebo group. On the 5th day, nasal obstruction and drainage
      were significantly better in the antibiotic-treated group. In addition, a
      statistically significant difference in the endoscopic scores was noted between
      the treatment and placebo groups on days 5 and 12. CONCLUSION: The use of an
      antibiotic (amoxicillin/clavulanate) in the postoperative period is able to
      improve the outcome in the early blood crust healing phase: nasal obstruction and
      drainage are reduced and the endoscopic score objectively showed a faster
      recovery.

PMID- 20819472
TI  - Restoration of nasal cytology after endoscopic turbinoplasty versus laser
      assisted turbinoplasty.
AB  - BACKGROUND: Insult from surgical trauma leads to a degeneration of the nasal
      epithelium, resulting in morphological-volumetric changes involving the entire
      cell or a specific cell component. Alterations in normal nasal mucosa were
      assessed by nasal cytology and other functional tests after either endoscopic
      turbinoplasty or laser-assisted turbinoplasty for reducing inferior turbinate
      enlargement. METHODS: A total of 150 patients with chronic nasal obstruction due
      to inferior turbinate hypertrophy were randomly assigned to undergo laser
      assisted turbinoplasty or endoscopic turbinoplasty. Preoperative and
      postoperative assessment at 1 and 3 months follow-up included active anterior
      rhinomanometry, measurement of mucociliary transport time (MCTt), and nasal
      cytology to determine whether improved nasal breathing was accompanied by a
      restoration of preoperative nasal cytology and MCTt. One year after the
      operation, nasal cytology was repeated to definitively evaluate the presence of
      surgery-related cytological damage. RESULTS: At both postoperative visits, nasal
      resistance had decreased similarly in both treatment groups; mean MCTt was
      significantly shorter in the endoscopic turbinoplasty-treated group (p < 0.05);
      at both visits, the number of altered ciliated cells had increased in the laser
      assisted turbinoplasty-treated group but decreased in the endoscopic
      turbinoplasty-treated group, which, unlike the laser-assisted turbinoplasty
      treated group, was also noted to have progressed toward a significant improvement
      in the goblet-to-ciliated cell ratio (p < 0.01). CONCLUSION: When compared with
      laser-assisted turbinoplasty, endoscopic turbinoplasty is a conservative
      technique for inferior turbinate reduction that allows better restoration of
      preoperative nasal cytology and shorter MCTt.

PMID- 20819473
TI  - Report on the house-dust mite nasal provocation test.

PMID- 20819474
TI  - The Munker-White effect and chromatic induction share similar nonlinear response
      properties.
AB  - The brightness or color appearance of a region may be altered by the presence of
      a pattern surrounding it in the visual field. The Munker-White effect (grating
      surround) and brightness or color induction from concentric annuli ('bull's-eye'
      surround) are two examples. We examined whether these two phenomena share similar
      properties. In the asymmetric matching experiment, the task of an observer was to
      adjust the appearance of a matching patch to match the appearance of a test patch
      embedded in one of the two types (square wave grating or concentric annuli) of
      inducing surrounds (inducers). The inducer modulated in one of three color
      directions (isochromatic: +/-(L + M + S) and isoluminance: +/-(L - M) or +/-S).
      Each inducer type and color direction had two opposing phases and four contrast
      levels. The results show that the induced appearance shift increases as a power
      function of the inducer contrast, regardless of the spatial configuration of the
      inducer. Further analysis showed that a sensitivity modulation model of lateral
      interaction could explain both induction effects.

PMID- 20819475
TI  - Detecting sudden changes in dynamic rotation displays.
AB  - Four experiments and controls were run in order to determine the ability of the
      visual system to detect slight changes in three-dimensional (3D) rotating stimuli
      in comparison to two-dimensional (2D) controls. A small number of observers
      (between 5 and 8) viewed computerized displays of pixel-defined transparent
      rotating spheres or circular patches of pixels drifting linearly in opposite
      directions. Halfway through the circuit of rotation a letter was briefly
      displayed and the rotation continued with some change introduced. Our results
      showed that for horizontal shifts of the stimulus on the X-axis, changes in the
      axis of rotation, and additions/deletions of pixels, observers were better at
      detecting the changes associated with 3D motion than 2D motion. There was no good
      2D control for approaching and receding stimuli, but on the basis of other
      results it was concluded that 3D movement had no advantage. It is suggested that
      rotation in 3D is more readily monitored by the visual system than simultaneous
      2D motions in opposite directions.

PMID- 20819476
TI  - Fechner's aesthetics revisited.
AB  - Gustav Fechner is widely respected as a founding father of experimental
      psychology and psychophysics but fewer know of his interests and work in
      empirical aesthetics. In the later 1800s, toward the end of his career, Fechner
      performed experiments to empirically evaluate the beauty of rectangles,
      hypothesizing that the preferred shape would closely match that of the so-called
      'golden rectangle'. His findings confirmed his suspicions, but in the intervening
      decades there has been significant evidence pointing away from that finding.
      Regardless of the results of this one study, Fechner ushered in the notion of
      using a metric to evaluate beauty in a psychophysical way. In this paper, we
      recreate the experiment using more naturalistic stimuli. We evaluate subjects'
      preferences against models that use various types of object complexity as
      metrics. Our findings that subjects prefer either very simple or very complex
      objects runs contrary to the hypothesized results, but are systematic none the
      less. We conclude that there are likely to be useful measures of aesthetic
      preference but they are likely to be complicated by the difficulty in defining
      some of their constituent parts.

PMID- 20819477
TI  - [Current status of surgical management of esophageal cancer in China and the
      future strategy].

PMID- 20819478
TI  - [Analysis of expression profiles of some tumor growth-related genes after
      silencing of pleiotrophin in human small cell lung cancer H446 cells].
AB  - OBJECTIVE: To investigate the changes in expression profiles of angiomotin
      (Amot), schlafen5 (Slfn5), metalloproteinase-9 (MMP-9) and vascular endothelial
      cell growth factor (VEGF), which are genes associated with angiogenesis, tumor
      growth and invasion, after gene silencing of pleiotrophin (PTN) in human small
      cell lung cancer H446 cells. METHODS: PTN expression in H446 cells was determined
      by RT-PCR and Western blot. After constructing a lentiviral vector interfering
      PTN expression, it was packaged into virus in 293T cells. Then the virus was used
      to infect human small cell lung cancer H446 cells. The expressions of Amot,
      Slfn5, MMP-9 and VEGF were detected by RT-PCR in normal non-interference group,
      negative control group, PTN-interference group and group combining PTN
      interference and chemotherapy. RESULTS: The results of RT-PCR and Western blot
      test showed that PTN expression in H446 cells was high. The interference
      efficiency of constructed ShRNA sequences (GCAGCTGTGGATACTGCTGAA) targeting PTN
      was as high as 72.1% and 59.2% at the mRNA and protein levels, respectively, in
      H446 cells. Compared with the negative control group, the expressions of Slfn5
      and MMP-9 in H446 cells were increased by 165.1% and 47.3%, while the ones of
      Amot and VEGF were down-regulated by 33.1% and 26.6%, respectively, after gene
      silencing of PTN. The changes of gene expression profile became more evident when
      chemotherapy was superimposed on PTN interference. CONCLUSION: Gene silencing of
      PTN using siRNA lentiviral expressing vector can influence the expression of
      proliferation and metastasis-related genes in human small cell lung cancer H446
      cells.

PMID- 20819479
TI  - [GM-CSF gene-modified dendritic cell vaccine enhances antitumor immunity in
      vitro].
AB  - OBJECTIVE: To investigate if granulocyte-macrophage colony stimulating factor (GM
      CSF) gene-modified dendritic cells (DC) enhance antitumor immunity in vitro.
      METHODS: Mice were injected with chemokine ligand 3 (CCL3) via the tail vein.
      Fresh B220(-)CD11c(+) cells were sorted from the peripheral blood mononuclear
      cells (PBMCs) and cultured into DCs by cytokines.DCs were transfected with AdGM
      CSF gene at different ratios of multiplicity of infection (MOI) to determine the
      optimal gene transfection conditions, and the expression of GM-CSF was detected
      after transfection. The variation of GM-CSF gene-modifiedDCs were analyzed by
      morphological examination, phenotype analysis, and mixed lymphocyte reaction
      (MLR).DCs were loaded with gastric cancer antigen obtained by freezing and
      thawing method. The killing effect of DCs vaccine-stimulated T lymphocytes on
      gastric cancer cells was assessed by MTT assay. INF-gamma production was
      determined with the INF-gamma ELISA kit. RESULTS: B220(-)CD11c(+) cells increased
      obviously after CCL3 injection. The ELISA results showed that after GM-CSF gene
      modification, DCs could produce high level of GM-CSF. When DCs were transfected
      with AdGM-CSF gene at MOI equal to 100, the GM-CSF level in culture supernatants
      reached saturation [(130.00 +/- 12.61) pg/ml]. After GM-CSF gene-modification,
      DCs tend to be more maturated as detected by morphological observation and
      phenotype analysis. At the same time, the capacity of activating the
      proliferation of allogeneic T lymphocytes was enhanced greatly. T lymphocytes
      stimulated by DCs transfected with GM-CSF gene showed a specific killing effect
      on gastric carcinoma cells and produced high level of INF-gamma [(1245.00 +/-
      13.75) pg/ml]. CONCLUSION: After GM-CSF gene modification, DCs can produce high
      level of GM-CSF, which tend to be more maturated, and the capacity of activating
      the proliferation of allogeneic T lymphocytes is enhanced greatly. GM-CSF gene
      modified DCs can induce specific CTL to target tumor cells in vitro.

PMID- 20819480
TI  - [Antitumor effect of DHA compound in vitro and in vivo and its mechanism].
AB  - OBJECTIVE: To study the anticancer effect in vitro and in vivo and mechanism of
      DHA compound. METHODS: Cervical cancer cell line HeLa cells, glioma cell line
      U251 cells and mouse hepatoma H(22) tumor were used in this study. Transmission
      electron microscopy and fluorescence microscopy were used to observe the
      morphological changes of cell apoptosis. Western blot was used to detect the
      expression of caspase-3. RT-PCR was used to determine the effect on Bcl-2 and Bax
      mRNA transcription in U251. RESULTS: Antitumor effect was observed in vivo and in
      vitro. Typical morphological changes were seen in cancer cells. The level of
      caspase-3 was significantly increased and the content of Bcl-2 mRNA was decreased
      significantly, while the content of Bax mRNA was significantly increased in the
      U251 cells after treatment with DHA compound. CONCLUSION: DHA compound can
      inhibit the growth of some types of tumors and the increase of caspase-3 and Bax
      mRNA and decrease of Bcl-2 mRNA may be involved in its mechanism of action.

PMID- 20819481
TI  - [A study of cervical cancer screening algorithms].
AB  - OBJECTIVE: To assess the feasibility and accuracy of different cervical cancer
      screening algorithms suitable for different regions, and promote the prevention
      and control of cervical cancer in China. METHODS: Using the data of a cross
      sectional comparative trial of multiple techniques to detect cervical
      intraepithelial neoplasia in Xiangyuan County, Shanxi Province, conducted in
      1999, to evaluate the feasibility and accuracy of different cervical cancer
      screening algorithms. All the women were screened by six screening tests,
      including liquid based cytology (LBC), fluorescence spectroscopy, visual
      inspection with 5% acetic acid staining (VIA), colposcopy, self-sampled HPV DNA
      and clinician-sampled HPV DNA test, and each woman had histopathological
      diagnosis. Different screening algorithms were developed by combining the
      screening tests in parallel or in serial, and the performance indexes of the
      algorithms such as sensitivity, specificity, colposcopy referral rate and
      receiver operating characteristic (ROC) curve for detecting the high grade
      lesions (>or= CIN 2) were compared. RESULTS: Among the algorithms combined by LBC
      and HPV DNA testing, for the combination in parallel (either cytology was greater
      than ASC-US or HPV positives), its sensitivity was 100%, specificity was 68.6%,
      and colposcopy referral rate was 34.4%; for the algorithm of LBC as primary
      screening test, with ASC-US women triage by HPV DNA testing, its sensitivity was
      93.0%, specificity was 89.9%, and colposcopy referral rate was 13.7%; for the
      algorithm of HPV DNA testing as the primary screening test, with HPV positive
      women triage by LBC, its sensitivity was 91.7%, specificity was 93.0%, and
      colposcopy referral rate was 10.6%. ROC analysis showed that LBC primary testing
      followed by HPV triage and HPV primary testing followed by LBC triage were much
      better than the combination in parallel (P = 0.0003, P = 0.0002). Among the
      algorithms with LBC or HPV DNA testing solely as primary screening test, the
      sensitivity, specificity and colposcopy referral rate of LBC were 94.2%, 77.3%,
      25.7% and 87.2%, 93.5%, 10.0%, respectively, for cutoff by ASC-US or by LSIL; the
      sensitivity, specificity and colposcopy referral rate of HPV DNA testing were
      97.6%, 84.8%, 18.8% and 83.5%, 85.9%, 17.1%, respectively, for clinician-sampled
      and self-sampled. Clinician-sampled HPV DNA testing was better than LBC cutoff by
      ASC-US or self-sampled HPV DNA testing (P = 0.005, P = 0.002). Among the
      algorithms combined by VIA and HPV DNA testing, the sensitivity, specificity and
      colposcopy referral rate were 70.9%, 74.3% and 27.6% for VIA alone as primary
      screening test; the sensitivity, specificity and colposcopy referral rate were
      65.9%, 95.2% and 7.4% for HPV as primary screening test with HPV positive women
      triage by VIA. HPV primary testing followed by VIA triage was better than VIA
      alone (P = 0.004). CONCLUSION: Considering the health-resource settings and
      women's preference, both HPV primary testing followed by LBC triage and LBC
      primary testing followed by HPV triage are suitable for developed regions,
      moderately developed regions may choose either LBC or HPV as the screening
      approach, VIA is a suitable primary screening test in less developed regions, and
      HPV primary testing followed by VIA triage will be more effective if low cost HPV
      test is available in the future.

PMID- 20819482
TI  - [Expression of E-cadherin in nasopharyngeal carcinoma and its relationship with
      cervical lymph node metastasis].
AB  - OBJECTIVE: To investigate the expression of E-cadherin in nasopharyngeal
      carcinoma (NPC) and its relationship with cervical lymph node metastasis.
      METHODS: The expression of E-cadherin in 80 patients with NPC was detected by
      immunohistochemistry. RESULTS: Lower expression of E-cadherin was associated with
      advanced N-stage of the tumor (P = 0.018). There was no significant correlation
      between the expression of E-cadherin and lymph node size (P = 0.435). The
      expression of E-cadherin was higher in patients with cervical lymph node
      metastasis limited to a single area than that distributing in some scattered
      areas (P = 0.000). There was a trend that the expression of E-cadherin in the
      cases with the tumor and lymph nodes in the same side was higher (56.5%) than
      that in the patients with bilateral lymph node metastases (32.6%), however, the
      difference was not significant (P = 0.059). The expression rates of E-cadherin in
      patients with lymph node metastasis in levels II, III and Va were higher than
      that in levels I, IV, Vb and VI, but with a non-significant difference (P =
      0.059). CONCLUSION: The expression of E-cadherin has influence on the lymph node
      metastasis in nasopharyngeal carcinoma. E-cadherin expression is negatively
      correlated with the numbers of the lymph node metastases and the metastasis
      distance, i.e. a lower expression of E-cadherin leads to an advanced N-stage. The
      lymph node metastasis of nasopharyngeal cancer from above to below is more
      considerably influenced by E-cadherin expression than the metastasis towards
      contralateral lymph nodes.

PMID- 20819483
TI  - [Analysis of the relationship between expression of caveolin-1 and prognosis in
      bladder transitional cell carcinoma].
AB  - OBJECTIVE: To analyze the relationship between expressions of caveolin-1 and
      prognosis in bladder transitional cell carcinoma (BTCC). METHODS: The expression
      of caveolin-1 was detected in 85 cases of BTCC. 64 cases of primary BTCC were
      followed-up after operation. The tumor-free survival time in recurrent BTCC
      patients was observed. RESULTS: The positive expression rates of caveolin-1 in
      primary and recurrent BTCC were 32.8% and 61.9%, respectively, with a significant
      difference (P < 0.05). There was a significant difference (P < 0.05) between the
      tumor-free survival times in the groups with positive and negative expressions of
      caveolin-1. The half-, 1-, 2- and 3-year tumor-free survival rates in the group
      with positive expression of caveolin-1 were 90.4%, 80.9%, 66.3% and 56.1%,
      respectively. The half-, 1-, 2-, and 3-year tumor-free survival rates in the
      group with negative expression of caveolin-1 were 97.7%, 95.4%, 81.4% and 79.0%,
      respectively. The tumor-free survival rate in the group with positive expression
      of caveolin-1 was significantly lower than that in the group with negative
      expression of caveolin-1 (P < 0.05). CONCLUSION: Positive expression of caveolin
      1 in BTCC can be regarded as a high risk factor of recurrence of BTCC. Positive
      expression of caveolin-1 in BTCC is correlated with the prognosis of BTCC, and
      BTCC patients with positive expression of caveolin-1 should be followed-up after
      operation.

PMID- 20819484
TI  - [Exploration of the classification of gross tumor volume and pathological staging
      of esophageal carcinoma].
AB  - OBJECTIVE: Using the volume calculating function of treatment planning system of
      3DCRT to work out the value of GTV standard classifications and to provide the
      reference for clinical staging of esophageal carcinoma. METHODS: Six hundred and
      seven patients underwent radical resection of thoracic esophageal carcinoma in
      our hospital, and their pre-operative CT images were transmitted in digital
      format to the three-dimensional conformal radiotherapy planning system by the
      network. Esophageal lesion GTV targets were outlined, and their volumes were
      automatically computed by the planning system. Compared the differences of the
      GTV volumes in different pathological T stages, and analyzed the relationship
      between GTV volumes and pathological T stages. According to the median volume of
      GTV at different pathological T stages, divided the values of GTV volume
      corresponding to different T stages and selected the suitable classification
      standard of GTV volume. RESULTS: The esophageal carcinoma GTV length, maximum
      diameter and volume were related to pathological T staging and with a positive
      correlation (all P < 0.001). The Spearman correlation coefficient (r) was 0.376,
      0.466 and 0.464, respectively, P < 0.001. Except that the length, maximum
      diameter and volume of GTV in pathological T3 and T4 had no significant
      difference, other indicators of the pathological T stages showed significant
      differences between the groups (P < 0.001). According to the median volume of GTV
      at different pathological T stages, the GTV volumes were divided into three
      grades: <or= 5.0 cm(3), 5.1 - 13.0 cm(3), and > 13.0 cm(3). When compared them
      with pathological T1, T2, and T3-T4 stages, the coincidence rate was 73.8%. The
      consistency was good between the GTV volume grades and pathological T stages
      (Kappa = 0.40, P < 0.001). The overall 5-year survival rates of GTV grades 1, 2,
      3 were 78.1%, 31.5% and 33.5%, respectively (P < 0.0001). If the GTVs were
      divided into four grades: <or= 5.0 cm(3), 5.1 - 13.0 cm(3), 13.1 - 39.0 cm(3),
      and > 39.0 cm(3), the coincidence rate of GTV volume grades and pathology T
      staging was only 54.7%, and the consistency was poor, Kappa = 0.24, P < 0.001.
      The overall 5-year survival rate of GTV 1, 2, 3, 4 were 78.1%, 31.5%, 36.2% and
      27.5%, respectively (P < 0.0001). CONCLUSION: The length, maximum diameter and
      volume of esophageal carcinoma GTV are related to pathological T staging with a
      positive correlation. The classification that esophageal carcinoma GTVs divided
      into three grades has a good coincidence with the pathological T staging.

PMID- 20819485
TI  - [Impact of the number of resected and involved lymph nodes on the outcome in
      patients with stage II non-small cell lung cancer].
AB  - OBJECTIVE: The aim of this study was to evaluate if factors associated with
      dissected lymph nodes affect the outcome of completely resected stage II (T1-2N1)
      non-small cell lung cancer (NSCLC). METHODS: Clinical data of 121 patients with
      complete resection of stage II NSCLC in Sun Yat-sen University Cancer center from
      January 1998 to December 2004 were reviewed retrospectively and the effect of
      factors of dissected lymph nodes on overall survival (OS) and disease-free
      survival (DFS) of NSCLC was analyzed. RESULTS: The univariate analysis
      demonstrated that the total number of removed lymph nodes, the number of involved
      N1 lymph nodes, the ratio of involved N1 lymph nodes and the total number of
      removed N2 lymph nodes were significant prognostic factors for OS. In the
      multivariate analysis, the total number of removed lymph nodes and the number of
      involved N1 lymph nodes were independent prognostic factors for OS. In both of
      univariate and multivariate analyses, tumor size, the total number of removed
      lymph nodes and the number of involved N1 lymph nodes were independent prognostic
      factors for DFS. CONCLUSION: For patients with completely resectable stage II
      NSCLC, 10 or more lymph nodes should be removed at the surgical resection. Total
      number of removed lymph nodes >or= 10 is a favorable prognostic factor and
      involved N1 >or= 3 is an adverse one.

PMID- 20819486
TI  - [Clinical study of pineal region tumors: experience with 132 patients].
AB  - OBJECTIVE: To review the clinical manifestations, imaging, tumor markers,
      treatment methods, pathology results and clinical curative effects of pineal
      region tumors and to evaluate the characteristics and intervention strategies for
      those tumors. METHODS: The clinicopathological data of 132 patients with pineal
      region tumor treated in our department between January 2000 and May 2008 were
      retrospectively studied. RESULTS: A moderate predominance in males was presented.
      The clinical manifestations of the disease included increased intracranial
      pressure and ocular movement impairment. There were some features but no
      regularity and specific appearance on imaging including CT and MRI. 88.6% of
      patients associated with hydrocephalus. A high serum level of alpha-fetoprotein
      (AFP) was presented in 14 cases and high HCG in 9 cases. Eighteen cases received
      direct radiation therapy and 7 had radiotherapy post biopsy. 107 cases were
      treated surgically and 63 cases received postoperative adjuvant treatment. 114
      cases had pathology results including 56 germ cell tumors. The patients were
      followed up for 12 approximately 132 months. Recurrence developed in 23 cases and
      12 cases died. The 5-year survival rate was 89.3%. CONCLUSION: Pineal region
      tumors are often associated with hydrocephalus and this makes preoperative
      diagnosis difficult. Imaging examination may help diagnosis but less specific.
      Germ cell tumors may diagnosed by some tumor markers. Radiation therapy is the
      choice of treatment for pure germinomas. Other types of pineal region tumors
      should receive surgical treatment. Postoperative adjuvant treatment based on
      pathology can provide a good prognosis in pineal region tumor.

PMID- 20819487
TI  - [Clinical features and prognosis of solid-pseudopapillary tumor of the pancreas].
AB  - OBJECTIVE: To study the clinicopathological and immunohistochemical features,
      histogenesis and biological behavior, clinical treatment and prognosis of solid
      pseudopapillary tumor of the pancreas (SPT). METHODS: Routine HE and
      immunohistochemical (SP) stainings were used in the pathological examination of
      18 cases of SPT. Their clinical data were retrospectively analyzed. All the 18
      postoperative patients were followed-up for 3 months to 10 years with an average
      of 29.2 months. RESULTS: There were 16 females and 2 males, age ranging from 9 to
      65 years with mean age of 25.3 years. Abdominal pain and palpable mass were among
      the major complains. Tumors were encapsulated and mixed with solid and cystic
      tissues. Histological features were pseudopapillary structure with a
      fibrovascular core. Immunhistologically, most tumors were positive for alpha-AT,
      alpha-ACT and Vim, with a high percentage of 94.4%. The eighteen cases were
      followed-up from 3 to 120 months. Five cases received reoperation after
      recurrence, and 14 cases were alive. Maximum survival time was 121 months and the
      minimum survival time was 3 months, with a median survival time of 23.0 months.
      The 5-year survival rate was 72.2%. A Kaplan-Meier analysis revealed that
      patient's age, tumor size, pathologic features, metastasis were major prognostic
      factors for SPT. CONCLUSION: SPT is a tumor of low-grade malignancy and may be
      derived from multipotent stem cells. SPT most frequently affects young female,
      and has distinct clinicopathologic manifestation with excellent prognosis after
      surgical treatment.

PMID- 20819488
TI  - [Clinical features and prognostic factors of angioimmunoblastic T cell lymphoma].
AB  - OBJECTIVE: To retrospectively analyze the clinical features and prognostic
      factors of patients with angioimmunoblastic T-cell lymphoma (AITL). METHODS: The
      clinicopathological and follow-up data of 18 AITL patients undergoing integrated
      treatment from Feb. 1998 to April 2009 in our department were retrospectively
      analyzed. All of the patients received CHOP-like regimens as initial
      chemotherapy, including 4 once treated with radiotherapy and 1 with high dose
      therapy followed by autologous stem cell transplantation (HDT-ASCT) as upfront
      consolidation therapy. B-cell, T-cell and NK-cell subgroup proportions in the
      peripheral blood were tested by flow cytometry in 6 patients. RESULTS: The median
      age of the 18 patients was 55 years, male and female ratio was 2.6:1. Seventy-two
      percent of the patients were in an advanced stage. 72% of them had B symptoms,
      69% hypergammaglobulinemia, 60% elevated LDH and 47% anemia. Forty-four percent
      achieved CR after initial treatment with CHOP-like regimens. With the median
      follow-up of 26 months, the overall 2-year survival and disease free survival
      (DFS) rates were 62.2% and 44.4%, respectively. In the univariate analysis, only
      age > 30 years and primary refractory disease adversely affected overall survival
      (OS); age > 30 years, advanced stage, B symptoms and splenomegaly adversely
      affected DFS. Four patients suffered from severe pneumonia during treatment, 2 of
      them died of respiratory failure. Flow cytometry of peripheral blood lymphocytes
      showed that 5 of the 6 tested cases had decreasing proportion of CD3(+)CD4(+) T
      cells, B cells and NK cells but elevated CD3(+)CD8(+) T cells. Two heavily
      treated patients achieved partial and complete response by thalidomide therapy,
      with a progression free survival (PFS) of 2 and 6+ months, respectively.
      CONCLUSION: AITL patients do not response well to CHOP-like regimens
      chemotherapy. Age < 30 years and sensitive to initial chemotherapy are associated
      with prolonged OS. Effectiveness of thalidomide in the treatment of AITL deserves
      further investigation. Peripheral blood lymphocytes test indicates that AITL
      patients suffered from both natural and acquired immune defects.

PMID- 20819489
TI  - [A prospective comparison between surgery alone and postoperative
      chemoradiotherapy for locally advanced esophageal squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the role of postoperative chemoradiotherapy (CRT) as a
      multimodality treatment option for locally advanced thoracic esophageal squamous
      cell carcinoma (ESCC) by a prospective comparison between surgery alone and
      postoperative CRT. METHODS: Using preoperative computed tomography (CT)-based
      staging criteria, 158 patients with ESCC (stage II-III) were enrolled in this
      prospective study. With informed consent, the patients were randomized into two
      groups: postoperative CRT (78 cases) and surgery alone (S, 80 cases). After a few
      minor adjustments to the enrolled patients, the actual patients of postoperative
      CRT group and S group were 74 cases and 77 cases, respectively. Comparison of the
      complications, local recurrence rate, distant metastasis rate, survival rate and
      progression-free survival in the two groups was carried out. RESULTS: With a
      median follow-up of 37.5 months, the 1-, 3-, 5-, 10-year overall survival (OS)
      rates were 91.0%, 62.8%, 42.3%, 24.4% and 87.5%, 51.3%, 33.8%, 12.5% for the
      postoperative CRT and S arm, respectively. A significant difference in OS was
      detected between the two arms (P = 0.0276). There was a significant difference of
      progression-free survival (PFS) between the two arms (P = 0.0136). The local
      recurrence rates in the postoperative CRT group and S group were 14.9% and 36.4%,
      respectively (P < 0.05). No significant difference was detected between the
      complications of the two groups (P > 0.05). Toxicities of chemoradiotherapy in
      the postoperative CRT arm were moderate, which can be relieved rapidly by
      adequate therapy. CONCLUSION: Rational application of postoperative
      chemoradiotherapy can provide a benefit in progression-free survival and overall
      survival in patients with locally advanced esophageal squamous cell carcinoma.

PMID- 20819490
TI  - [Comparison of the therapeutic effects of PTBD and PTBS in treatment of malignant
      obstructive jaundice].
AB  - OBJECTIVE: To summarize and compare the short-term and long-term clinical
      efficacy of percutaneous transhepatic biliary drainage (PTBD) and percutaneous
      transhepatic biliary stent (PTBS) in the treatment of malignant obstructive
      jaundice. METHODS: 210 cases of malignant obstructive jaundice underwent
      interventional therapy, of which 161 cases of drainage catheters placement and 49
      cases of metallic stent implantation. Follow-up information was obtained through
      telephone review or check-up records. RESULTS: The technical success rate of
      technique was 100%. At 3 - 5 days after treatment, the serum total bilirubin in
      15 metallic stent-treated patients was decreased by (178.04 +/- 42.32)
      micromol/L, and direct bilirubin by (83.97 +/- 23.63) micromol/L. Compared with
      those of 28 cases treated with drainage catheters: (95.67 +/- 34.28) micromol/L
      and (49.84 +/- 28.21) micromol/L, there were statistically significant
      differences between the two groups (P = 0.017 and P = 0.035). At 6 - 9 days after
      treatment, the serum total bilirubin in 28 cases of metallic stent group was
      decreased by (188.22 +/- 79.90) micromol/L, and that in 126 cases of drainage
      catheter group decreased by (141.39 +/- 65.32) micromol/L. The difference was
      statistically significant (P = 0.014). But the decline value of direct bilirubin
      had no significant difference. The median patency period and the median survival
      time of the drainage catheter group were 60 and 148 days, respectively, those of
      metallic stent group were 197 days and 245 days. There were statistically
      significant differences between the two groups (P < 0.05). CONCLUSION: The
      results of this study indicate that the short-term and long-term efficacies of
      metallic stent implantation are better than those of catheter drainage technique.

PMID- 20819491
TI  - [Analysis of the prophylactic effect of nucleosides against reactivation of HBV
      in HBsAg-positive patients with non-hepatic tumors after chemotherapy].
AB  - OBJECTIVE: To investigate the efficacy of nucleosides as a prophylactic agent
      against reactivation of hepatitis B virus (HBV) in HBsAg-positive patients with
      non-hepatic tumors after chemotherapy. METHODS: Fifty-eight patients with non
      hepatic tumors were divided into prevention group and control group. The patients
      of prevention group received nucleosides as a prophylactic agent before
      chemotherapy and were compared with the control ones about the clinical
      manifestation of HBV reactivation. Then, the patients of the control group were
      divided into three groups according to antiviral drugs, use or not and time of
      the use. The patients having HBV reactivation but never received nucleosides were
      included in the group A, the patients receiving nucleosides after having HBV
      reactivation were divided into the group B, and the patients receiving
      nucleosides before HBV reactivation were divided into the group C. The
      progression, prognosis and curative effect among the three groups were compared.
      RESULTS: The rate of HBV reactivation, incidence of severe hepatitis, mortality
      rate of the control group (61.1%, 27.8%, 16.7%) were significantly higher than
      those of the prevention group (13.6%, 0, 0), and liver dysfunction was more
      serious than that in the prevention group. In the control group, all the 5
      patients of group A died of liver failure. Of the 13 patients in the group B, 4
      cases suffered from severe hepatitis and 1 of them died of the disease. Of the 18
      patients in the group C, 4 cases suffered from HBV reactivation, but the clinical
      manifestation was milder than that of the group B. CONCLUSION: Nucleosides can be
      used as a prophylactic measure to prevent HBV reactivation. If chemotherapy had
      begun, the use of nucleosides may reduce the risk of HBV reactivation. Even if
      patients had suffered from HBV reactivation, the use of nucleosides may still
      help the recovery of liver function and improve prognosis.

PMID- 20819492
TI  - [Value of 18F-FETNIM PET-CT for detection of tumor hypoxia in non-small-cell lung
      cancer].
AB  - OBJECTIVE: To assess the feasibility of [(18)F]fluoroerythronitroimidazole ((18)F
      FETNIM) with integrated positron emission tomography and computed tomography (PET
      CT) imaging in detection of hypoxia in non-small-cell lung cancer (NSCLC)
      patients. METHODS: Forty-two patients with newly diagnosed NSCLC underwent (18)F
      FETNIM PET-CT before treatment. Nineteen patients rested for approximately 120
      minutes before undergoing PET-CT, 23 patients underwent 2 sequential PET-CT scans
      at 60 minutes and 120 minutes after intravenous injection (18)F-FETNIM. (18)F
      FETNIM uptake was quantified by calculating the maximum standardized uptake value
      in the tumor (SUVmax-T) and contralateral normal lung tissue (SUVmax-N). Regions
      of interest (ROIs) were drawn in the tumor and contralateral position and the
      radioactivity ratio of tumor to normal (T/N) was calculated. RESULTS: SUVmax-T
      (2.43 +/- 1.34) was significantly higher than SUVmax-N (0.87 +/- 0.46, P < 0.001)
      at 120 min. SUVmax-T (2.80 +/- 1.09) and SUVmax-N (1.16 +/- 0.56) at 60 min were
      significantly higher than SUVmax-T (2.61 +/- 1.10) and SUVmax-N (P < 0.01) at 120
      min. T/N (2.56 +/- 0.71) at 60 min was higher than that at 120 min (2.48 +/-
      0.60), but the difference between them was not significant (P = 0.324).
      CONCLUSION: Our results indicate that (18)F-FETNIM PET-CT may be a useful tool
      for evaluating hypoxia and may be a means to target specifically tumor cells
      resistant to conventional treatment before and during ongoing therapy in NSCLC.

PMID- 20819493
TI  - [Comparison of the therapeutic effects of pleural perfusion of NDP and cDDP in
      NSCLC patients with malignant pleural effusion].
AB  - OBJECTIVE: To compare the therapeutic effects of pleural perfusion of NDP and
      cDDP in non-small cell lung cancer (NSCLC) patients with malignant pleural
      effusion, their quality of life and toxic side effects. METHODS: Sixty-eight
      NSCLC patients with malignant pleural effusion after chest drainage were randomly
      divided into two groups according to the pathological types: 34 cases in the NDP
      (Group A) and cDDP groups (Group B), 34 cases each. They were treated with NDP
      (40 mg/m(2)) and dexamethasone (10 mg) dissolved in 40 ml normal saline, or cDDP
      (40 mg/m(2)) and dexamethasone (10 mg) dissolved in 40 ml of normal saline,
      respectively, through pleural perfusion weekly for 2-4 weeks. Routine and
      symptomatic treatment was used in all the patients. The therapeutic effects, life
      quality and toxic side effects were evaluated. RESULTS: The response rates of
      groups A and B were 88.23% and 61.7%, respectively, (P < 0.01). The rates of
      toxic side effects in groups A and B were 39.6% and 41.9%, respectively, (P >
      0.05). However, the rates of gastrointestinal side effects of the two groups were
      5% and 12.9%, respectively, (P < 0.05). The Karnofsky scores of group A were
      higher than that in group B (P < 0.05). The survival time of group A was
      significantly longer than that of group B. CONCLUSION: Pleural perfusion with NDP
      is a good treatment method with milder toxicity for patients with malignant
      pleural effusion caused by NSCLC.

PMID- 20819494
TI  - [Evaluation of the value of ultrasound-guided core needle biopsy in the diagnosis
      of breast lesions].
AB  - OBJECTIVE: To investigate the accuracy, consistency and related affecting factors
      in pathological results of breast lesions diagnosed by ultrasound-guided core
      needle biopsy (CNB) and conventional excision histopathology. METHODS: The
      clinical data of 177 consecutive cases of breast lesions examined by ultrasound
      guided CNB and subsequently excised were reviewed from Jan. 2003 to Nov. 2009.
      The agreement of pathological diagnosis between the CNB and subsequent excision
      pathology was analyzed. RESULTS: There were 136 cancers in the final diagnosis
      after surgical excision among 386 breast lesions and 129 of them were diagnosed
      by CNB. The sensitivity (true positive) of CNB was 94.9%, false negative rate was
      5.1%, specificity (true negative) was 100%, false positive rate 0, Youden's index
      was 0.949, and positive predictive value and negative predictive value were 100%
      and 85.4%, respectively. Condensation rate was 96.0% and Kappa value was 0.895.
      CONCLUSION: Ultrasound-guided CNB with histopathological assessment is accurate
      in diagnosis of breast lesions and has a great consistency with conventional
      excision pathology. It is a reliable method for the diagnosis of breast lesions
      to avoid an over-reliance on excision pathological examination.

PMID- 20819495
TI  - [Vacuum-assisted biopsy and wire localization for the diagnosis of non-palpable
      breast lesions].
AB  - OBJECTIVE: To compare the effectiveness and accuracy of the use of vacuum
      assisted biopsy (VAB) versus wire localization (WL) in the diagnosis of non
      palpable breast lesions (NPBL). METHODS: Ninety-seven consecutive women with NPBL
      were randomized into VAB group and WL group. All specimens were identified by
      mammography. The patients were requested to score the cosmetic appearance of
      their breast after operation, and a numerical rating scale was used to measure
      pain on the first postoperative day. Underestimation rates for atypical ductal
      hyperplasia (ADH) and ductal carcinoma in situ (DCIS) were recorded if open
      surgical biopsy revealed DCIS and invasive cancer, respectively. Clear margins
      were also recorded in the two groups. RESULTS: VAB and WL located all the NPBL
      successfully. In the VAB group, the specimen volume was smaller than that of the
      WL group (2.3 cm(3) vs. 18.4 cm(3), P = 0.03). Underestimation rates of ADH and
      DCIS in the VAB group were 16.7% and 11.1%, respectively. The diagnostic
      accordance rate of VAB was 97.9%, the false negative rate was 2.1%, and there was
      no false positive case. The means of the numerical rating pain scale were
      different in both groups (1.7 for VAB vs. 2.5 for WL, P = 0.02). When cosmetic
      results were taken into account, 40 VAB patients had excellent outcomes and 8
      good outcomes, compared with 25 excellent and 24 good for the WL group. There
      were better cosmetic outcomes with the VAB procedure (P < 0.05). CONCLUSION: VAB
      is highly reliable and may avoid diagnostic open surgery in the majority of
      patients with benign lesions. However, because of the underestimation of
      histologic diagnosis and tumor margin involvement, VAB can not be used to
      completely substitute wire localization.

PMID- 20819496
TI  - [Improvement of the axillary lymph node dissection during modified radical
      mastectomy].

PMID- 20819497
TI  - [Significance of retroperitoneal lymph node excision in the treatment of
      gynecological malignancies].

PMID- 20819498
TI  - Chronic obstructive pulmonary disease in China: a tale of two people.

PMID- 20819499
TI  - Asymptomatic patients of chronic obstructive pulmonary disease in China.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) has a variable natural
      history and not all individuals follow the same course. This study aimed to
      identify the prevalence and characteristics of asymptomatic COPD patients from a
      population-based survey in China. METHODS: A multistage cluster sampling strategy
      was used in a population from seven different provinces/cities. All residents
      (over 40 years old) were interviewed with a standardized questionnaire and
      spirometry. Post-bronchodilator forced expiratory volume in 1 second
      (FEV(1))/forced vital capacity (FVC) of less than 70% was defined as the
      diagnostic criterion of COPD. All COPD patients screened were divided into
      symptomatic group and asymptomatic group according to the presence or absence of
      chronic respiratory symptoms. Socio-demographic, personal and exposure variables
      were collected and analyzed. RESULTS: Among the 1668 patients who were diagnosed
      with COPD from the 25 627 sampling subjects, 589 (35.3%) were asymptomatic. The
      age, sex, body mass index (BMI), rural and urban distributions, smoking habit and
      education levels were similar in the two groups. A total of 64.7% of the
      asymptomatic patients had no comorbidities. Cardiovascular diseases and lung
      cancer were more common among symptomatic COPD patients than asymptomatic group.
      Asymptomatic COPD group were less likely to present with poor ventilation in the
      kitchen, a family history of respiratory disease and recurrent childhood cough.
      Asymptomatic COPD patients had significantly higher FEV(1) (73.1% vs. 61.0%), FVC
      (91.9% vs. 82.0%), and a higher ratio of FEV(1)/FVC (62.9% vs. 58.7%) (all P <
      0.001) than symptomatic group. More asymptomatic patients were underdiagnosed
      (91.9% vs. 54.3%, P < 0.001) than symptomatic patients. CONCLUSIONS: This large
      population-based survey confirmed a high prevalence of asymptomatic COPD patients
      in China. More use of spirometry screening test may be important to the early
      detection of COPD.

PMID- 20819500
TI  - Quantitative differentiation of dendritic cells in lung tissues of smokers with
      and without chronic obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is thought to be an
      inflammatory immune response disease. In most cases, the disease is caused by
      cigarette smoke, but it has been demonstrated that only 10% to 20% of smokers
      will definitely suffer from COPD. Dendritic cells (DCs) are considered to be the
      promoter of immune responses. However, the underlying mechanisms involved are
      still unrevealed. In this study, we aimed to investigate the quantitative
      differentiation of pulmonary DC in smokers with or without COPD to explore the
      possible role of DCs in smokers suffering COPD. METHODS: Peripheral lung
      specimens from non-smokers without airflow obstruction (control group, n = 7),
      smokers without airflow obstruction (smoker group, n = 7) and patients with COPD
      (COPD group, n = 7) were investigated to detect the quantity of S-100 and CD1a
      positive cells by immunohistochemical or immunofluorescent assay. RESULTS: In
      smokers with COPD, the number of S-100(+) DCs was higher than in the controls and
      smokers without COPD (P < 0.01 and P < 0.05) and there was a higher number of S
      100(+) DCs in smokers with COPD than in smokers without COPD, but without a
      significant difference (P > 0.05). An inverse correlation was found between the
      number of DCs and forced expiratory volume in the first second (FEV(1))% pred (r
      = -0.75, P < 0.05), which was also found between the number of DCs and
      FEV(1)/forced vital capacity (FVC) (r = -0.72, P < 0.05). The mean number of
      CD1a(+) DCs, increased from non-smokers to non-COPD smokers to COPD patients,
      with significant differences between each group (P < 0.01). CONCLUSIONS: The
      quantity of DCs significantly increased in smokers with COPD compared with non
      smokers or smokers without COPD. The results suggest that DCs may play an
      important role in the pathogenesis of smoking-induced COPD, and the upregulation
      of DCs may be a potential maker to identify the smokers who have more liability
      to suffer from COPD.

PMID- 20819501
TI  - Prognosis and staging of superficial endobronchial lung cancer: the impact of
      invasion depth, tumor diameter, and coexistent pneumonitis or atelectasis.
AB  - BACKGROUND: There are few reports discussing the surgical pathological
      characteristics of superficial endobronchial lung cancer (SELC) defined as cancer
      growth limited to the bronchial wall. Its prognosis and corresponding TNM staging
      have not been fully clarified. Little is known as to whether T status is impacted
      by the existence of associated atelectasis or pneumonia (which might be
      controversial, indicating either T1 or T2), and circumstantial invasion depth.
      METHODS: Between 1988 and 2007, 81 out of 8817 surgically treated patients met
      SELC criteria; there was no detectable invasion beyond the bronchial wall. A
      retrospective review was performed and follow-up information was collected.
      RESULTS: The overall five-year survival rate of 81 patients was 85.6%; for N0M0
      (n = 67), N1M0 (n = 7) and N2M0 (n = 7) patients, they were 89.3%, 75.0% and
      60.0%, respectively. Intraluminal tumor size measured from 0.4 to 3.0 cm;
      obstructive atelectasis or pneumonia was noted in 14 patients. The presence of
      tumor-associated obstructive atelectasis or pneumonia did not have a significant
      impact upon prognosis (P = 0.96), nor did the greatest diameter of the tumor (P =
      0.70). Histology showed carcinoma in situ (level one) in 13 cases; invasion of
      the submucosal layer (level two) in 12, involvement of the muscular layer (level
      three) in 20, invasion into the space between the muscular layer and cartilage
      (level four) in 21, and bronchial cartilage infiltration in 15 (level five). In
      cases without lymphnode metastases, five-year survival was 100% for the first
      three levels and 84.0% and 61.3% for the level four and level five. CONCLUSIONS:
      Relative to TNM-based prognostic data, superficial endobronchial lung cancer
      exhibits increased five-year survival rates, and therefore should be placed at
      the forefront among tumors in the T1 class, regardless of tumor size or the
      presence of secondary obstructive atelectasis or pneumonia. Lymphnode metastasis
      is associated with a worse prognosis. Survival is negatively impacted by tumor
      infiltration depth into the bronchial wall.

PMID- 20819502
TI  - Prevalence of deep venous thrombosis in patients with acute exacerbation of
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (COPD) is
      always associated with a high incidence and mortality. Because of the presence of
      some concomitant risk factors such as immobilization, bronchial superinfection,
      patients who are admitted for acute exacerbations of COPD are generally
      considered to be at moderate risk for the development of venous thromboembolism.
      In this study, we investigated the prevalence and the clinical manifestations of
      deep venous thrombosis (DVT) in patients with acute exacerbation of COPD.
      METHODS: From March 2007 to March 2009, 520 consecutive patients were included in
      this study. On admission, color Doppler ultrasound of lower extremities in all
      cases was performed for diagnosing DVT. Patients with DVT were compared with
      those without DVT from such aspects as demographics, symptoms, physical signs and
      risk factors. RESULTS: Among the 520 patients, DVT was found in 46 cases (9.7%).
      In patients with DVT, the duration of hospitalization was longer (P = 0.01), and
      the mechanical ventilation requirement increased (P < 0.001). Other indicators
      for patients with more possibility of DVT were immobility exceeding 3 days (P <
      0.001); pneumonia as concomitance (P = 0.01); respiratory failure type II (P =
      0.013); current smoking (P = 0.001). Lower extremity pain was more common in DVT
      cases in comparison to those without DVT (34.8% vs. 15.2%, P = 0.01).
      CONCLUSIONS: The acute exacerbation of COPD patients, who were immobilized for
      over 3 days, complicated by pneumonia and had respiratory failure type II, had a
      higher risk of DVT. In addition, DVT detection awareness should be increased in
      cases that had a lower extremity pain.

PMID- 20819503
TI  - Characteristics and risk factors of cerebrovascular accidents after percutaneous
      coronary interventions in patients with history of stroke.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) is a well-established method
      for managing coronary diseases. However, the increasing use of PCI has led to an
      increased incidence of acute cerebrovascular accidents (CVA) related to PCI. In
      this study, we investigated the characteristics and risk factors of CVA after PCI
      in patients with known stroke history. METHODS: Between January 1, 2005 and March
      1, 2009, 621 patients with a history of stroke underwent a total of 665 PCI
      procedures and were included in this retrospective study. Demographic and
      clinical characteristics, previous medications, procedures, neurologic deficits,
      location of lesion and in-hospital clinical outcomes of patients who developed a
      CVA after the cardiac catheterization laboratory visit and before discharge were
      reviewed. RESULTS: Acute CVA was diagnosed in 53 (8.5%) patients during the
      operation or the perioperative period. Seventeen patients suffered from transient
      ischemic attack, thirty-four patients suffered from cerebral infarction and two
      patients suffered from cerebral hemorrhage. The risk factors for CVA after PCI in
      stroke patients were: admission with an acute coronary syndrome, use of an intra
      aortic balloon pump, urgent or emergency procedures, diabetes mellitus, and poor
      left ventricular systolic function, arterial fibrillation, previous myocardial
      infarction, dyslipidemia, tobacco use, and no/irregular use of anti-platelet
      medications. CONCLUSIONS: The incidence of CVA during and after PCI in patients
      with history of stroke is much higher than that in patients without history of
      stroke. Patients with atrial fibrillation, previous myocardial infarction,
      diabetes mellitus, dyslipidemia, tobacco use, and no or irregular use of anti
      platelet medications were at higher risk for recurrent stroke. This study showed
      a strong association between acute coronary syndromes and in-hospital stroke
      after PCI.

PMID- 20819504
TI  - Comparison of the ability of wavelet index and bispectral index for reflecting
      regain of consciousness in patients undergone surgery.
AB  - BACKGROUND: Wavelet index (WLI) is a new parameter for monitoring depth of
      anesthesia based on Wavelet analysis. We observed the change of WLI and
      bispectral index (BIS) in patients regain of consciousness (ROC) in the absence
      of frontalis electromyographic (EMG) interference. The aim of this study was to
      compare the ability of WLI and BIS for reflecting ROC in patients undergone
      surgery. METHODS: Twelve patients who were scheduled for maxillofacial surgeries
      were enrolled in the study. BIS and WLI values were monitored continually. After
      being given midazolam and remifentanil, patients were asked to squeeze the
      investigator's hand ever 30 seconds. Patients were continuously given propofol
      until loss of consciousness (LOC1). Tunstall's isolated forearm technique was
      used to test the surgical consciousness in patients. After total muscle
      relaxation, endotracheal intubations were performed, and the patients were
      connected to a ventilator. Then, propofol was withdrawn until the patients showed
      regain of consciousness (ROC1) and an awareness reaction. After the command test,
      patients were readministered with propofol until loss of consciousness (LOC2).
      After surgery, all of the sedatives were withdrawn, and the patients were let to
      regain consciousness (ROC2). RESULTS: The BIS values of twelve patients at ROC1
      after using muscle relaxant were much lower than those at LOC1 and ROC2 without
      using muscle relaxant, showing statistical significance (P < 0.05). Meanwhile,
      the WLI values of twelve patients at ROC1 after using muscle relaxant were much
      higher than those at LOC1 and equal to ROC2 without using muscle relaxant,
      showing statistical significances (P < 0.05) between ROC1 and LOC1. CONCLUSIONS:
      This study showed that under muscle relaxation or facial paralysis, when there is
      no EMG signal, BIS can not accurately reflect regain of consciousness in surgical
      patients, but WLI can reflect it accurately. So WLI may have advantages for
      reflecting state of consciousness in surgical patients.

PMID- 20819505
TI  - Assessment of bone marrow changes in postmenopausal women with varying bone
      densities: magnetic resonance spectroscopy and diffusion magnetic resonance
      imaging.
AB  - BACKGROUND: Recent studies suggest that bone marrow adipose tissue might play a
      role in the pathogenesis of osteoporosis. There are inconsistent findings on the
      relationship among marrow fat content, bone mineral density and apparent
      diffusion coefficient (ADC). This study aimed to prospectively explore the
      efficacy of MR spectroscopy (MRS) and diffusion-weighted MR imaging (DWI) in
      detecting vertebral marrow changes in postmenopausal women with varying bone
      densities. METHODS: Both MRS and DWI of the lumber spine were performed in 102
      postmenopausal women (mean age, (67.3 +/- 6.5) years; range, 55 - 83 years), who
      underwent dual X-ray absorptiometry. Marrow fat content and ADC were compared and
      correlated among three groups: 24 with normal bone density, 31 with osteopenia
      and 47 with osteoporosis. RESULTS: Vertebral marrow fat content was significantly
      increased in the osteoporotic group ((65.60 +/- 7.68)%, P < 0.001) and the
      osteopenic group ((57.68 +/- 6.45)%, P < 0.001), when compared with the normal
      bone density group ((51.67 +/- 3.27)%). ADC values were significantly decreased
      in the osteoporotic group ((0.39 +/- 0.03) x 10(-3)mm(2)/s, P < 0.001) and in the
      osteopenic group ((0.42 +/- 0.02) x 10(-3)mm(2)/s, P < 0.001), when compared with
      the normal bone density group ((0.47 +/- 0.03) x 10(-3)mm(2)/s). The marrow fat
      content negatively correlated with both bone density (r = -0.731, P < 0.001) and
      marrow ADC (r = -0.572, P < 0.001). The bone density positively correlated with
      the ADC values (r = 0.802, P < 0.001). CONCLUSIONS: Postmenopausal women
      experience a corresponding increase in vertebral marrow fat content as the bone
      density decreases. Marrow fat content and ADC correlate to the bone density. MRS
      and DWI may indirectly assess the early bone marrow changes in postmenopausal
      women.

PMID- 20819506
TI  - A comparative study of influential factors correlating with early and late
      hypothyroidism after (131)I therapy for Graves' disease.
AB  - BACKGROUND: (131)I therapy is recognized as the simplest, safest, least
      expensive, and most effective treatment, and accepted by more and more patients.
      However its curative effect is influenced by many factors, therefore there are
      some difficulties for doctors to establish individual treatment strategy. The
      aims of this study were to determine the incidence of early and late
      hypothyroidism after (131)I treatment for Graves' disease (GD) and to compare
      their correlation, to observe and analyze the influential factors and to
      understand the predictabilities of them. METHODS: Five hundred GD patients (144
      males, 356 females; age (41.2 +/- 12.3) years) received (131)I treatment for the
      first time. The therapeutic procedure was carried out as the following:
      undergoing (131)I uptake test to obtain maximum of thyroid uptake value and
      effective half-life (EHL) time; estimating the thyroid's weight by
      ultrasonography; determination of thyroid hormones and correlative antibodies;
      pre-therapy physical examination; thyroid imaging; calculating (131)I therapeutic
      dosage; per os uptake of the determined (131)I dosage; follow-up appraisal of
      curative effect. The observing parameters included age, gender, thyroid weight,
      GD duration, condition of onset, state of disease, course of treatment, EHL time,
      maximum of thyroid uptake value, (131)I dosage and titer of correlative
      antibodies. We sorted out the data and used both univariate and multivariate
      analysis to evaluate them statistically. RESULTS: The incidence rates of early
      and late hypothyroidism were 33.2% and 6.6% respectively after (131)I treatment
      and approximately 22.2% cases of late hypothyroidism developed from early
      hypothyroidism. The influential factors of early hypothyroidism included course
      of GD, the highest thyroid uptake ratio of (131)I, EHL time and thyroid microsome
      antibody (TMAb), etc. A multivariate analysis on late hypothyroidism showed that
      female patients, with recurrence after anti-thyroid drug treatment and higher
      thyroid weight, had lower possibility of late hypothyroidism after (131)I
      therapy. CONCLUSIONS: The incidence of early hypothyroidism is higher than that
      of late hypothyroidism. The highest thyroid uptake ratio of (131)I, EHL and TMAb
      will increase the possibility of early hypothyroidism, while GD course is the
      protective factor. Higher (131)I dosage, longer EHL and higher TMAb titer will
      also increase the possibility of late hypothyroidism. The multi-perspective and
      multi-factor analysis has the benefit to establish individualized treatment
      strategy.

PMID- 20819507
TI  - Coronary artery bypass grafting for Kawasaki disease.
AB  - BACKGROUND: Kawasaki disease (KD) is the leading cause of pediatric ischemic
      heart disease. The incidence of serious coronary sequelae is low and about 2% -
      3% of patients with KD, but once myocardial infarction occurs in children, the
      mortality is quite high and 22% at the first infarction.This study aimed to
      evaluate the efficacy of coronary artery bypass grafting (CABG) in patients with
      KD. METHODS: Eight patients with a history of KD underwent CABG between October
      1997 and July 2005. The number of bypass grafts placed was 2 to 4 per patient
      (mean 2.5 +/- 0.8). Various bypass grafts were used in patients, i.e. the left
      internal mammary artery (LIMA) in 3 patients, bilateral internal mammary artery
      (IMA) in 2 patients, LIMA plus gastroepiploic artery (GEA) in 1 patient and total
      saphenous vein grafts (SVGs) in 2 patients. The combined procedures included
      ventricular aneurysmectomy in 1 patient, mitral valve plasty in 1 and right
      coronary aneurysmectomy in 1. One patient was not able to wean from
      cardiopulmonary bypass (CPB), after being supported with intra-aortic balloon
      pump (IABP), the patient was weaned from CPB successfully. RESULTS: One patient
      died of low cardiac output syndrome and acute renal failure 19 days after
      operation. Other patients recovered and were discharged uneventfully. During the
      follow-up that ranged from 3 to 57 months (mean 27 months), clincal angina
      disappeared or improved. Cardiac function was in Class I - II (NYHA). CONCLUSION:
      CABG is a safe and effective procedure for Kawasaki coronary artery disease.
      However long-term results need to be followed up.

PMID- 20819508
TI  - Effects of traditional Chinese medicine on intestinal mucosal permeability in
      early phase of severe acute pancreatitis.
AB  - BACKGROUND: Traditional Chinese medicine has been used widely for many years in
      China to treat acute pancreatitis. We have investigated the effects of Dachengqi
      decoction on intestinal mucosal permeability and outcome in patients with severe
      acute pancreatitis (SAP). METHODS: Forty patients with sustained SAP that
      required admission to the surgical intensive care unit were enrolled
      prospectively in the study. All of these patients were divided randomly into the
      Dachengqi decoction group (n = 20) and control group (n = 20) on admission.
      Intestinal permeability was assessed by measuring absorption of two metabolically
      inert markers, lactulose (L) and mannitol (M), which were administered orally.
      Serum concentrations of endotoxin (lipopolysaccharide, LPS) and the ratio of
      lactulose to mannitol in urine (L/M) were detected in all patients. RESULTS:
      Compared with those in the control group, urinary L/M ratio decreased
      significantly in the Dachengqi decoction group on the 7th day after admission (P
      = 0.001). Also, serum concentrations of LPS were reduced on the 5th and 7th day
      after admission (P = 0.006, P = 0.008, respectively). Incidence of multiple organ
      dysfunction syndrome (MODS) and pancreatic infection was significantly lower in
      the Dachengqi decoction group compared with those in the control group (P =
      0.038,P = 0.025, respectively). CONCLUSION: Dachengqi decoction may promote the
      recovery of intestinal mucosal permeability and decrease the incidence of MODS
      and pancreatic infection in patients with SAP.

PMID- 20819509
TI  - Role of cyclooxygenase-2 signaling pathway dysfunction in unexplained recurrent
      spontaneous abortion.
AB  - BACKGROUND: Experimental evidence indicates that cyclooxygenase-2 (COX-2) plays a
      critical role in blastocyst implantation; however, little is known of the role of
      COX-2 in unexplained recurrent spontaneous abortion (URSA). METHODS: We evaluated
      the expression level and potential signaling pathway of COX-2 in 30 cases of URSA
      who were excluded the abnormality of chromosomes, anatomy, endocrine, infectious,
      autoimmune diseases and in 30 normal pregnancies. RESULTS: The mRNA and the
      protein expression level of COX-2 in the URSA group (-0.238 +/- 0.848, 0.368 +/-
      0.089, respectively) were significantly lower than that in the control group
      (1.943 +/- 3.845, 1.046 +/- 0.108, respectively) (both, P < 0.01). The expression
      of prostaglandins PGF(2a), PGD(2), PGE(2), and PGI(2), in the URSA group ((2326.0
      +/- 295.6) pg/ml, (2164.0 +/- 240.5) pg/ml, (238.7 +/- 26.4) pg/ml, (2337.0 +/-
      263.0) pg/ml, respectively) were significantly lower than that in the control
      group ((3450.0 +/- 421.7) pg/ml, (3174.0 +/- 415.6) pg/ml, (323.5 +/- 43.8)
      pg/ml, (3623.0 +/- 460.4) pg/ml, respectively) (P < 0.05). The mRNA expression
      level of PPARbeta and RXRalpha (0.859 +/- 0.653, -0.172 +/- 0.752, respectively)
      in URSA group was significantly lower than that in the control group (1.554 +/-
      1.735, 0.777 +/- 2.482, respectively) (both P< 0.05). The mRNA and protein
      expression levels of vascular endothelial growth factor-A (VEGF-A) in the URSA
      group (2.010 +/- 1.522, 0.35 +/- 0.46) was significantly lower than that in the
      control group (4.569 +/- 2.430, 0.750 +/- 0.350) (both P < 0.05). CONCLUSIONS:
      COX-2 and the COX-2-derived PGI(2) signaling pathway possibly play an important
      role in successful embryo implantation, and their decreased expression may result
      in URSA. The decreased expression may influence the expression of VEGF-A which
      interferes with placental angiogenesis causing failure of embryo implantation,
      leading to spontaneous abortion.

PMID- 20819510
TI  - Angiographic leakage of polypoidal choroidal vasculopathy on indocyanine
      angiography.
AB  - BACKGROUND: There is no detailed report about the angiographic leakage of
      polypoidal choroidal vasculopathy (PCV) lesions on indocyanine green (ICG)
      angiography. This study aimed to investigate the angiographic leakage of
      polypoidal lesions in PCV on ICG angiography. METHODS: One hundred and forty-four
      eyes of 137 patients diagnosed as PCV were prospectively observed. Fundus
      examination, fluorescein angiography, and ICG angiography were performed. Leakage
      of polypoidal lesions and clinical features were recorded according to the
      angiograms. RESULTS: In all 144 eyes, 110 eyes showed angiographic leakage
      (leakage group) on ICG angiography and three subtypes of leakage group were
      noted, which were polypoidal dilations leakage (47 eyes, 42.7%), branching
      vascular networks leakage (14 eyes, 12.7%) and leakage of both (49 eyes, 44.5%).
      The other 34 eyes showed regression of polypoidal lesions (regression group). In
      leakage group, the rates of pigment epithelial detachment (PED), best corrected
      visual acuity (BCVA) < 0.1 and old subretinal hemorrhages were 56.4% (62 eyes),
      19.1% (21 eyes), and 4.6% (5 eyes) respectively, compared with 8.8% (3 eyes), 50%
      (17 eyes) and 38.2% (13 eyes) of regression group (P < 0.001). The history of
      regression group was significantly longer (P < 0.001). CONCLUSIONS: Angiographic
      leakage and regression can be observed in PCV lesions. Leakage of both polypoidal
      dilations and branching vascular networks is the most common subtype in leakage
      group. PCV in leakage group is more likely to be related to PED, better BCVA and
      shorter history, while PCV regression group tends to relevant to old subretinal
      hemorrhage, worse BCVA and longer history. This may reflect that the former is
      active or in the early course while the later is resting or in the late phase of
      PCV.

PMID- 20819511
TI  - Aspirin and pravastatin reduce lectin-like oxidized low density lipoprotein
      receptor-1 expression, adhesion molecules and oxidative stress in human coronary
      artery endothelial cells.
AB  - BACKGROUND: Oxidative stress and inflammation are important steps in the
      pathogenesis of atherosclerosis. We postulated that therapeutic concentrations of
      aspirin and pravastatin, especially in combination, may suppress oxidative stress
      and inflammation in endothelial cells, and this concept was examined in human
      coronary artery endothelial cells (HCAECs). METHODS: Human coronary artery
      endothelial cells were cultured and treated with oxidized-low density lipoprotein
      (ox-LDL, 60 microg/ml for 24 hours) alone, or pre-treated with aspirin (1, 2 or 5
      mmol/L), pravastatin (1, 5 or 10 micromol/L) or their combination (1 mmol/L
      aspirin and 5 micromol/L pravastatin), followed by ox-LDL treatment. After
      respective treatment, superoxide anion production, p38 mitogen activated protein
      kinase and transcription factor NF-kappaB activation, protein expression of
      lectin-like ox-LDL receptor-1 (LOX-1) and adhesion molecules, and monocyte
      adhesion were measured. RESULTS: Ox-LDL treatment greatly elicited its receptor
      LOX-1 expression, superoxide anion production and inflammatory response, which
      were minimally affected by low concentration of aspirin (1 mmol/L) or pravastatin
      (5 micromol/L), but were markedly decreased by their combination. Activation of
      p38 mitogen activated protein kinase and NF-kappaB, the expression of
      intercellular adhesion molecule-1 and monocyte chemotactic protein-1, which were
      only mildly affected by aspirin or pravastatin alone, were significantly
      attenuated by their combination. As a consequence, monocyte adhesion to
      endothelial cells was markedly attenuated by the combination of the two agents.
      Well-known anti-oxidants alpha-tocopherol and gamma-tocopherol had similar
      inhibitory effects on ox-LDL-mediated oxidative stress and LOX-1 expression as
      well as monocyte adhesion as did the combination of aspirin and pravastatin.
      CONCLUSIONS: These studies point to a positive interaction between aspirin and
      pravastatin with regard to endothelial biology. Anti-oxidant and subsequent anti
      inflammatory effect may be one of the potential underling mechanisms.

PMID- 20819512
TI  - Effects of the TREM-1 pathway modulation during empyema in rats.
AB  - BACKGROUND: The activation of triggering receptor expressed on myeloid cells-1
      (TREM-1) in the presence of microbial components amplifies the inflammatory
      response. The aim of the present study was to investigate the effect of the
      modulation of the TREM-1 pathway during empyema in rats. METHODS: Adult male
      Wistar rats were subjected to empyema induced by intrapleural injection of
      Pseudomonas aeruginosa and Staphylococcus aureus. The animals were treated with
      LP17 (a synthetic TREM-1 inhibitor), a control peptide, or a vehicle (normal
      saline). Differential cell count, flow cytometry and histological examination
      were performed to evaluate local inflammatory alterations. Concentrations of
      tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in both pleural
      effusion and serum were measured by enzyme-linked immunosorbent assay. RESULTS:
      Although differential counts of each type of leukocytes in pleural effusion were
      not affected by LP17, a marked reduction in neutrophil numbers was seen in LP17
      treated rats due to the reduction of both pleural effusion volume and total cell
      numbers. LP17 administration impaired concentration elevation in tumor necrosis
      factor-alpha, interleukin-1beta, and interleukin-6 in both pleural effusion and
      serum. It was found that survival rate in LP17 treated rats was much higher than
      that in control rats. CONCLUSION: The modulation of the TREM-1 pathway by the use
      of LP17 appears to be beneficial during empyema in rats in attenuating pleural
      and systemic inflammatory responses.

PMID- 20819513
TI  - Overexpression of parathyroid pituitary-specific transcription factor (Pit)-1 in
      hyperphosphatemia-induced hyperparathyroidism of chronic renal failure rats.
AB  - BACKGROUND: Hyperphosphatemia in renal failure has been identified as a major
      role in the pathogenesis of hyperparathyroidism that is independent of changes in
      serum calcium and 1,25(OH)(2)D(3). The aim of this study was to evaluate the
      expression of parathyroid Pit-1 in hyperphosphatemia-induced secondary
      hyperparathyroidism (SHPT) of chronic renal failure (CRF) rats. METHODS: Wistar
      rats with CRF induced by 5/6 nephrectomy were ramdomly fed with diet containing
      1.2% inorganic phosphate (Pi, high phosphate (HP) group, n = 9) or 0.2% Pi (low
      phosphate (LP) group, n = 9) for 10 weeks starting from the fourth week after the
      surgery. Another 7 nephrectomy rats with HP diet were intraperitoneally injected
      with phosphonoformic acid (PFA, the specific inhibitor of Pit-1, HP + PFA group)
      0.15 g/kg every other day for 10 weeks starting from HP diet. Another 6 HP rats
      injected with the same amount of normal saline as the control of the HP + PFA
      group (HP + saline group). At the same time, 9 rats with sham surgery received HP
      diet as the controls. At the 4th week and 14th week, blood was taken for
      measurement of serum creatinine (SCr), serum calcium (SCa), serum phosphorus
      (SPi), 1,25(OH)(2)D(3) and intact parathyroid hormone (iPTH). At the 14th week,
      two parathroid glands (PTGs) of each rat were removed by microsurgery, one gland
      for immunohistochemistry analysis of proliferating cell nuclear antigen (PCNA),
      the other one for detection of Pit-1 by Western blotting, and for the measurement
      of Pit-1 mRNA and PTH mRNA by real-time quantitative polymerase chain reaction.
      RESULTS: In nephrectomy rats, high dierary phosphate induced a marked increase in
      serum phosphate, iPTH, PTH mRNA and PCNA parathyroid cells, accompanying Pit-1
      and its mRNA in parathyroid gland increased significantly. However, serum Ca and
      1,25(OH)(2)D(3) remained unchanged. PFA decreased Pit-1 and its mRNA levels to
      reduce intact PTH, PTH mRNA and PCNA-positive parathyroid cells. CONCLUSIONS:
      Expression of parathyroid Pit-1 in hyperphosphatemia-induced SHPT of CRF rats was
      upregulated. Pit-1 may mediate the stimulation to parathyroid gland by
      hyperphosphatemia.

PMID- 20819514
TI  - Overexpression of connexin 45 in rat mesenchymal stem cells improves the function
      as cardiac biological pacemakers.
AB  - BACKGROUND: Extensive research toward creating a biological pacemaker by
      enhancement of inward depolarizing current has been performed. However, studies
      have mainly focused on inducing spontaneous activity and have not adequately
      addressed ways to improve pacemaker function. In this study we attempted to
      improve pacemaker function by altering connexin expression in rat mesenchymal
      stem cells (MSCs) to a phenotype similar to native sinus node pacemaker cells.
      METHODS: To generate a biological pacemaker, MSCs were transduced with a cardiac
      pacemaker gene-hyperpolarization-activated cyclic nucleotide-gated channel 4
      (HCN4), via transfection with a lentiviral vector. Funny current (I(f)) in
      HCN4(+) MSCs was recorded by voltage-clamp. Overexpression of connexin 45 (gene
      Gja7) in MSCs was achieved by transfection with the plasmid pDsRED2-N1-Gja7-RFP.
      Double-immunolabelling with anti-connexin 43 and anti-connexin 45 antibodies were
      used to identify the gap junction channels. The effects of the genetically
      modified MSCs on cardiomyocyte excitability were determined in MSCs cocultured
      with neonatal rat ventricular myocytes. Spontaneous action potentials of neonatal
      rat ventricular myocytes were recorded by current-clamp. RESULTS: High level time
      and voltage-dependent inward hyperpolarization current that was sensitive to 4
      mmol/L Cs(+) was detected in HCN4(+) MSCs, confirming that HCN4 acted as I(f)
      channels in MSCs. Connexin 43 and connexin 45 were simultaneously detected in
      CX45(+) MSCs. Beating frequency was (82 +/- 8) beats per minute (n = 5) in
      myocytes cocultured with non-transfected control MSCs, versus (129 +/- 11) beats
      per minute (n = 5) in myocytes cocultured with HCN4(+) MSCs. Myocytes cocultured
      with MSCs cotransfected with HCN4 and connexin 45 had the highest beating
      frequency at (147 +/- 9) beats per minute (n = 5). CONCLUSION: These findings
      demonstrate that overexpression of connexin 45 and subsequent formation of
      heteromeric connexin 45/connexin 43 gap junction channels in HCN4 expressing MSCs
      can improve their function as cardiac biological pacemakers in vitro.

PMID- 20819515
TI  - Changes in the expression of platelet-derived growth factor in astrocytes in
      diabetic rats with spinal cord injury.
AB  - BACKGROUND: Prospective mortality studies in the United States revealed that the
      mortality was elevated in diabetics compared to normal individuals following
      chronic spinal cord injury (SCI). Our study was conducted to investigate the
      levels of platelet-derived growth factor (PDGF) of astrocytes in SCI in
      streptozotocin (STZ)-induced diabetic rats. METHODS: Thirty male Sprague-Dawley
      (SD) rats were randomly divided into 3 groups: SCI group, diabetic SCI group, and
      sham operation control group. We employed STZ-induced diabetic SD rats and a
      weight-drop contusion SCI model. The rats were sacrificed on day 7 after the
      induction of SCI. Immunohistochemistry and Western blotting analysis were used to
      detect the PDGF expression level. Basso, Beattie and Bresnahan locomotor rating
      scale (BBB) was also used to evaluate the neurological recovery level of the
      rats. RESULTS: PDGF positive astrocyte numbers were significantly higher and PDGF
      staining was more intensive in astrocytes in the SCI group than in the diabetic
      SCI group (P < 0.05). The diabetic SCI group showed a slower recovery of motor
      function with a lower BBB score 7 days after acute spinal injury. CONCLUSIONS:
      PDGF is an important factor for the recovery of neurological function after acute
      spinal injury and hyperglycemia in diabetic rats could depress the expression of
      PDGF in injured spinal cord. This may help to explain the slower recovery and
      higher mortality in diabetics after SCI.

PMID- 20819516
TI  - Changes in functional connectivity of ventral anterior cingulate cortex in heroin
      abusers.
AB  - BACKGROUND: Previous studies with animal experiments, autopsy, structural
      magnetic resonance imaging (MRI) and task-related functional MRI (fMRI) have
      confirmed that brain functional connectivity in addicts has become impaired. The
      goal of this study was to investigate the alteration of resting-state functional
      connectivity of the ventral anterior cingulate cortex (vACC) in the heroin
      abusers' brain. METHODS: Fifteen heroin abusers and fifteen matched healthy
      volunteers were studied using vACC as the region-of interest (ROI) seed. A 3.0 T
      scanner with a standard head coil was the imagining apparatus. T2*-weighted
      gradient-echo planar imaging (GRE-EPI) was the scanning protocol. A ROI seed
      based correlation analysis used a SPM5 software package as the tool for all
      images processing. RESULTS: This study showed a functional connection to the
      insula vACC in heroin abusers. Compared with controls, heroin users showed
      decreased functional connectivity between the nucleus accumbens (NAc) and vACC,
      between the parahippocampala gyrus/amgdala (PHC/amygdala) and vACC, between the
      thalamus and vACC, and between the posterior cingulated cortex/precuneus (PCC/pC)
      and vACC. CONCLUSION: The altered resting-state functional connectivity to the
      vACC suggests the neural circuitry on which the addictive drug has an affect and
      reflects the dysfunction of the addictive brain.

PMID- 20819517
TI  - Safety and efficacy of laser and cold knife urethrotomy for urethral stricture.
AB  - BACKGROUND: Endoscopic treatment for urethral stricture, including cold knife and
      laser, poses a major challenge to clinical practice. Both the benefits and
      drawbacks of these two treatments remain controversial. This article aimed to
      compare the efficacy and safety of laser and cold knife urethrotomy for urethral
      stricture. METHODS: We searched PubMed (1966 - 2009), Embase (1980 - 2009),
      Cochrane Central Register of Controlled Trials (CCRCT, 2009 No.1) and Chinese
      Biomedical Literature Database (CBM) for laser and cold knife urethrotomy as
      treatment for male urethral stenosis, looking in the English literatures. Two
      reviewers independently screened the literatures and extracted information. Chi
      square test was used for statistical analysis with SPSS15.0. RESULTS: A total of
      44 articles, including of 3230 cases was retrieved. Success rate of patients
      treated with laser was 74.9% compared with 68.5% for cold knife, with very
      similar clinical results despite a statistically significant difference (P =
      0.004). The trend in success rate at a different follow-up time was similar
      between the two groups. No significant difference in success rate was found
      between the groups of repeat operation for recurrence cases, first P = 0.090 and
      second P = 0.459. The shorter the stricture length was (< 1 cm), the higher the
      success rate was (P < 0.0001). No significant difference in success rate between
      the laser and cold knife groups was found in neither bulbar nor membranous
      urethra, bulbar P = 0.660 and membranous P = 0.477. The rates of urinary
      incontinence, urinary extravasation, and urinary tract infection showed no
      significant difference (P = 0.259, P = 0.938, P = 0.653, respectively).
      CONCLUSIONS: Success rates for laser and cold knife were very similar despite
      being statistically different, with the groups having a similar trend in success
      rates at different follow-up time. Stricture location and history of endoscopic
      intervention did impact treatment outcome but was not significantly different.
      The two groups showed no significant difference in major complications.

PMID- 20819518
TI  - Significance of depression in obstructive sleep apnea patients and the
      relationship between the comorbidity and continuous positive airway pressure
      treatment.

PMID- 20819519
TI  - Overexpression of mclca3 in airway epithelium of asthmatic murine models with
      airway inflammation.

PMID- 20819520
TI  - Analgesic effect of parecoxib and flurbiprofen axetil for patients undergoing
      laparoscopic cholecystectomy and their influences on platelet aggregation.

PMID- 20819521
TI  - Appendiceal endometriosis differentially diagnosed from acute appendicitis.

PMID- 20819522
TI  - Clinical analysis of alveolar soft-tissue sarcoma of the uterine cervix: a case
      report.

PMID- 20819523
TI  - Recurrent pneumothorax as a presenting manifestation of active sarcoidosis: a
      case report and literature review.

PMID- 20819524
TI  - Emphasis should be placed on the prevention and treatment of complications after
      endovascular repair of aortic dissection.

PMID- 20819525
TI  - Downregulation of endothelin-1 by somatostatin improves liver function of
      recipients undergoing adult-to-adult living donor liver transplantation.
AB  - BACKGROUND: The aim of this study was to investigate the possible effect of
      somatostatin on the liver function of recipients undergoing living donor liver
      transplantation. METHODS: Forty recipients were randomized into group A (n = 20)
      and group B (n = 20). Recipients in group A received no somatostatin whereas
      somatostatin was administrated for recipients in group B perioperatively. Liver
      function, the plasma concentration of endothelin-1 and nitric oxide, the
      intragraft expressions of endothelin-1 and inducible nitric oxide syntheses at 2
      hours after declamping of the portal vein were compared between the two groups.
      RESULTS: Compared to group A, alanine transaminase values in group B were
      significantly reduced at 2 hours after portal vein declamping, at the end of the
      operation and postoperation day 1 (P < 0.05), whereas aspartate aminotransferase
      values in group B decreased at 30 minutes after portal vein clamping, at 2 hours
      after portal vein declamping and at the end of the operation (P < 0.05). Total
      bilirubin values in group B were reduced significantly at 2 hours after portal
      vein declamping and at the end of the operation when compared to group A (P <
      0.05). Intragraft expression of endothelin-1 was significantly downregulated at 2
      hours after declamping of the portal vein accompanied with a reduction of plasma
      concentration of endothelin-1 in the peripheral blood (P < 0.05). CONCLUSIONS:
      Somatostatin had a protective effect on liver function during the early phase
      after declamping of portal vein for recipients undergoing living donor liver
      transplantation, and the possible mechanism might be partially attributed to the
      downregulation of endothelin-1.

PMID- 20819526
TI  - Efficacy and feasibility of radiofrequency ablation for decompensated cirrhotic
      patients with hepatocellular carcinoma.
AB  - BACKGROUND: Most HCC patients with decompensation of liver function lost the
      chance of surgical and/or interventional treatment. The aim of this study was to
      evaluate feasibility and outcome of radiofrequency ablation (RFA) in treating
      hepatocellular carcinoma (HCC) patients with poor liver function (Child-Pugh
      class C), who are not suitable for surgery or hepatic artery chemo-embolization.
      METHODS: Thirteen HCC patients (the number of tumors was 17) with liver function
      of Child-Pugh C (scores: 10.2 +/- 0.4) were included in the study. Among the
      patients, 8 were male and 5 were female with the average age of (61.6 +/- 10.9)
      years old. The average size of HCC was (3.8 +/- 1.0) cm. Two patients were
      recurrent HCC and 30.8% of the patients had multiple tumors (2 - 3 tumors). All
      the patients were treated with RFA. RESULTS: There were 22 RFA sessions (1 - 4
      sessions per patient) in all, average ablations per tumor at first session was
      3.1. One week after RFA, the liver enzymes elevated in 9 patients (69.2%), in 7
      of them, the liver enzyme returned to pre-RFA level in 1 - 3 months. One month
      after RFA, the Child-Pugh grading was 10.3 +/- 0.8 (Child-Pugh C), while that of
      pre-RFA was 10.2 +/- 0.4 (Child-Pugh C), with no significant difference. Computer
      tomography (CT) one month after RFA showed that the tumor necrosis rate was 88.2%
      (15/17). Five patients had 2 - 4 repeated RFA due to HCC recurrence. During the
      follow-up of 2- 69 months in this group, survival rate of one year was 53.8%, two
      years was 30.8%, and three year was 15.4%. The incidence of RFA-related
      complications was 13.6% (3/22 sessions), including 1 case of GI hemorrhage and 1
      sub-capsular hemorrhage of the liver. One patient with HCC over 5 cm who had
      fever and liver abscess after RFA, and was dead 2 months later due to liver
      function failure. CONCLUSIONS: Minimal invasive RFA provides possible treatment
      modality for HCC patients with poor liver function, who are not candidates for
      surgical and/or interventional therapy. For large HCC, due to the required
      extended treatment region, special attention should be paid to the possibility of
      acute liver failure.

PMID- 20819527
TI  - Is it safe to perform operation for colorectal malignancy in Chinese patients
      without DVT prophylaxis? An 8-year experience from a regional hospital in Hong
      Kong.
AB  - BACKGROUND: Colorectal surgery was regarded as one of the high risk surgery for
      post-operative deep vein thrombosis (DVT) and pulmonary embolism. This study
      aimed at investigating the incidence of venous thromboembolism (VTE) after
      colorectal surgery for malignancy. METHODS: Data were collected from the
      prospective database of colorectal malignancy from 2000 to 2008. A total of 1421
      colorectal (open and laparoscopic) operations were performed for the colorectal
      malignancy without DVT prophylaxis. RESULTS: Only seven patients (0.5%) developed
      symptomatic DVT and one of them had complication of pulmonary embolism without
      mortality. Open operation for colorectal malignancy was identified as possible
      risk factor of DVT, however, risk factors like operative time, low anterior
      resection, sex, age etc. were not identified. CONCLUSION: Risk of venous
      thromboembolism after colorectal operation is low in Chinese of our locality and
      it might be safe to perform colorectal operation for malignancy without DVT
      prophylaxis.

PMID- 20819528
TI  - Reproducibility of the Nottingham modification of the Scarff-Bloom-Richardson
      histological grading system and the complementary value of Ki-67 to this system.
AB  - BACKGROUND: The reproducibility of the Nottingham modification of the Scarff
      Bloom-Richardson (NSBR) histological grading system for invasive breast cancer
      (IBC) adopted by the World Health Organization (WHO) has previously not been
      studied in Chinese hospitals. The proliferation marker, Ki-67, has been widely
      applied in detecting IBC. The objective of this study was to assess the
      reproducibility of the NSBR system among Chinese pathologists and the
      complementary value that Ki-67 brings to this system. METHODS: Four general
      pathologists graded 100 IBC cases independently, which had previously been graded
      by specialists in breast pathology. The interobserver reproducibility among four
      general pathologists and pairwise reproducibility between each of them and the
      specialists were assessed. The Ki-67 labeling index (Ki-67LI) was determined by
      immunohistochemistry, and its correlations with histological grade and survival
      were determined. RESULTS: With respect to interobserver reproducibility, NSBR
      grading was fairly reproducible (kappa = 0.34); as for the components of NSBR
      grading, agreement was best for tubule formation (kappa = 0.46), intermediate for
      nuclear pleomorphism (kappa = 0.42), and poorest for mitotic count (kappa =
      0.28). In terms of pairwise reproducibility, agreement was fair to substantial
      with NSBR grading (kappa = 0.30 - 0.69) and nuclear pleomorphism (kappa = 0.28 -
      0.69), moderate to substantial for tubule formation (kappa = 0.51 - 0.78), and
      slight to substantial for mitotic count (kappa = 0.19 - 0.71). There were
      characteristic Ki-67LI ranges for grades 1, 2 and 3 tumors. Univariate analysis
      showed that Ki-67 was able to divide grade 2 patients into two different
      prognostic subgroups. Multivariate analysis of grade 2 patients with negative
      lymph node demonstrated that Ki-67 was an independent prognosticator for overall
      survival. CONCLUSIONS: The reproducibility of grading by general pathologists
      could be enhanced. Specialization in breast pathology is essential for accurate
      grading and treatment for IBC. Ki-67, with proven prognostic significance, adds
      complementary value to the NSBR system.

PMID- 20819529
TI  - Coagulase-negative staphylococcus and enterococcus as predominant pathogens in
      liver transplant recipients with Gram-positive coccal bacteremia.
AB  - BACKGROUND: Gram-positive bacteria such as Staphylococcus aureus have been a
      common cause of infection among liver transplant (LT) recipients in recent
      decades. The understanding of local epidemiology and its evolving trends with
      regard to pathogenic spectra and antibiotic susceptibility is beneficial to
      prophylactic and empiric treatment for LT recipients. This study aimed to
      investigate etiology, timing, antibiotic susceptibility and risk factors for
      multidrug resistant (MDR) Gram-positive coccal bacteremia after LT. METHODS: A
      cohort analysis of prospectively recorded data was performed to investigate
      etiologies, timing, antibiotic susceptibility and risk factors for MDR Gram
      positive coccal bacteremia in 475 LT recipients. RESULTS: In 475 LT recipients in
      the first six months after LT, there were a total of 98 episodes of bacteremia
      caused by Gram-positive cocci in 82 (17%) patients. Seventy-five (77%) bacteremic
      episodes occurred in the first post-LT month. The most frequent Gram-positive
      cocci were methicillin-resistant coagulase-negative staphylococcus (CoNS, 46
      isolates), methicillin-resistant Staphylococcus aureus (MRSA, 13) and
      enterococcus (34, E. faecium 30, E. faecalis 4). In all Gram-positive bacteremic
      isolates, 59 of 98 (60%) were MDR. Gram-positive coccal bacteremia and MDR Gram
      positive coccal bacteremia predominantly occurred in patients with acute severe
      exacerbation of chronic hepatitis B and with fulminant/subfulminant hepatitis.
      Four independent risk factors for development of bacteremia caused by MDR Gram
      positive coccus were: LT candidates with encephalopathy grades II - IV (P =
      0.013, OR: 16.253, 95%CI: 1.822 - 144.995), pre-LT use of empirical antibiotics
      (P = 0.018, OR: 1.029, 95%CI: 1.002 - 1.057), post-LT urinary tract infections (P
      < 0.001, OR: 20.340, 95%CI: 4.135 - 100.048) and abdominal infection (P = 0.004,
      OR: 2.820, 95%CI: 1.122 - 10.114). The main infectious manifestations were
      coinfections due to gram-positive cocci and gram-negative bacilli. CONCLUSIONS:
      Methicillin-resistant CoNS and enterococci are predominant pathogens among LT
      recipients with Gram-positive coccal bacteremia. Occurrences of Gram-positive
      coccal bacteremia may be associated with the severity of illness in the
      perioperative stage.

PMID- 20819530
TI  - Stable transfection of estrogen receptor-alpha suppresses expression of
      cyclooxygenase-2 and vascular endothelial growth factor-C in MDA-MB-231 breast
      cancer cells.
AB  - BACKGROUND: Estrogen receptor (ER)-negative breast cancer cells are more
      aggressive than ER-positive cells. Elevated levels of cyclooxygenase-2 (COX-2)
      and vascular endothelial growth factor-C (VEGF-C) expression have been detected
      in cultured human breast cancer cells and are associated with negative hormone
      receptor status. In this study, we created ERalpha stable transfectants in MDA-MB
      231 cells to explore the effect of ERalpha on cell growth and COX-2 and VEGF-C
      expression. METHODS: The green fluorescent protein (GFP)-ERalpha plasmids were
      stably transfected into ER-negative MDA-MB-231 cells. The proliferation and
      migration of untransfected MDA-MB-231 cells, ERalpha-transfected MDA-MB-231 cells
      and ER-positive MCF-7 cells were determined. The expression of COX-2, and the
      levels of VEGF-C mRNA and the VEGF-C secretion concentration were assayed in
      these cell lines. RESULTS: The proliferation and migration capacities of ERalpha
      tranfected MDA-MB-231 cells were significantly decreased (P < 0.05). The
      expression of COX-2 was significantly lower in ERalpha-tranfected MDA-MB-231
      cells than in untranfected MDA-MB-231 cells. The mRNA and protein levels of VEGF
      C were lower in ERalpha-tranfected MDA-MB-231 cells than in untransfected MDA-MB
      231 cells (P < 0.05). CONCLUSIONS: ERalpha stable transfection inhibits
      proliferation and migration capacities of MDA-MB-231 cells and decreases
      expression of COX-2 and VEGF-C. The decreases of proliferation and migration
      capacities may be related to suppression of COX-2 and VEGF-C expression.

PMID- 20819531
TI  - Unilateral sacrospinous ligament fixation for treatment of genital prolapse.
AB  - BACKGROUND: Genital prolapse affects 30% of middle-aged and older women and is
      becoming a major public health concern. Sacrospinous ligament fixation is an
      effective and safe procedure for vaginal vault prolaps with a low recurrence and
      complication rate. This study aimed to investigate the efficacy and safety of
      unilateral sacrospinous ligament fixation (SSLF) for the management of pelvic
      organ prolapse (POP). METHODS: Forty patients with severe prolapse of pelvic
      organ undergoing unilateral SSLF were retrospectively studied. In this study, all
      patients were staged by the value of POP-Q. All procedures were performed by a
      senior physician. The characteristics of these patients and their immediate and
      short-term post-operative outcome were recorded. All patients were seen six weeks
      and six months after the surgery. The evaluation included standardized
      questionnaire and site-specific vaginal examination by one physician. RESULTS:
      The average operation time was 65-92 minutes. The average blood loss was 83-188
      ml. The average hospitalization time was 6.1 days. The average cost was 5885
      yuan. The average day of urethral catheter removal after the operation was 2.1
      days. The incidence of postoperative morbidity was 17.1%. One (2.4%) patient had
      hematoma in the right pelvic. The mean length of postoperative follow-up for 35
      patients was 13.1 months. The rate of follow-up was 87.5%. One (2.9%) patient
      showed recurrent vaginal vault prolapse six months after the surgery. The
      objective success rate of pelvic organ prolapse was 85% (34/40). There was
      significant difference between the POP-Q of Aa, Ba, Ap, Bp, and D before and
      after operation (P < 0.001). Five (14.3%) patients complained lower back pain,
      gluteal pain or right groin pain. Three (8.6%) patients developed de novo stress
      incontinence. Vaginal disabsorbable sutures were found in three (8.6%) patients.
      One (2.9%) patient had de novo urge incontinence. CONCLUSIONS: Unilateral SSLF
      was both cost and treatment effective management for severe pelvic organ
      prolapse, especially for severe ovaginae anterior prolapse and uterus prolapse of
      POP I, II or III. Main complications from this procedure included lower back
      pain, gluteal and groin pain and new onset of stress incontinence.

PMID- 20819532
TI  - Hemodynamic effects of stenting on wide-necked intracranial aneurysms.
AB  - BACKGROUND: Stent placement has been widely used to assist coiling in cerebral
      aneurysm treatments. The present study aimed to investigate the hemodynamic
      effects of stenting on wide-necked intracranial aneurysms. METHODS: Three
      idealized plexiglass aneurismal models with different geometries before and after
      stenting were created, and their three-dimensional computational models were
      constructed. Flow dynamics in stented and unstented aneurismal models were
      studied using in vitro flow visualization and computational fluid dynamics (CFD)
      simulations. In addition, effects of stenting on flow dynamics in a patient
      specific aneurysm model were also analyzed by CFD. RESULTS: The results of flow
      visualization were consistent with those obtained with CFD simulations. Stent
      deployment reduced vortex inside the aneurysm and its impact on the aneurysm sac,
      and decreased wall shear stress on the sac. Different aneurysm geometries
      dictated fundamentally different hemodynamic patterns and outcomes of stenting.
      CONCLUSIONS: Stenting across the neck of aneurysms improves local blood flow
      profiles. This may facilitate thrombus formation in aneurysms and decrease the
      chance of recanalization.

PMID- 20819533
TI  - Age-specific prevalence of human papillomavirus by grade of cervical cytology in
      Tibetan women.
AB  - BACKGROUND: Human papillomavirus (HPV) is believed to be the most common sexually
      transmitted infection. However, little is known about the prevalence and
      distribution of HPV types in China. We aimed to assess the prevalence and the
      distribution of HPV types as well as risks for abnormal cervical cytology in
      women who reside in the Tibetan Autonomous Region of China. METHODS: A cross
      sectional study was performed involving a sample of 3036 women. An
      epidemiological questionnaire was applied and cervical specimens were obtained
      for liquid-based cytology and HPV DNA detection. Statistical analysis included
      chi-square and Logistic regression model. RESULTS: In this population, 3.66%
      (111/3036) had atypical squamous cells of undetermined significance (ASCUS),
      1.45% (44/3036) low-grade squamous intraepithelial lesions (LSIL) and 1.09%
      (33/3036) had high-grade squamous intraepithelial lesions (HSIL). Tibetan women
      (5.74%, 137/2387) exhibited lower abnormal cytology rates than non-Tibetan women
      (8.01%, 52/649, P = 0.03). The overall prevalence of HPV infection was 9.19%
      (279/3036). We failed to identify any differences in HPV prevalence by age. In
      the groups with normal, ASCUS, LSIL and HSIL, the overall HPV prevalences were
      7.41% (211/2847), 24.32% (27/111), 56.82% (25/44) and 45.45% (15/33),
      respectively. HPV 16 (1.52%, 46/3036) was the most common type, and was also the
      most prevalent in women with ASCUS (8.11%, 9/111) and HSIL (15.15%, 5/33). The
      most common HPV type for Tibetan women was HPV 16 (1.42%, 34/2387), whereas for
      non-Tibetan individuals it was HPV 33 (2.31%, 15/649). Of the 279 HPV-infected
      women, 40 individuals (14.34%) presented with multiple HPV positivity. Women who
      had two pregnancies were more likely to have abnormal cytology smear (OR = 1.67;
      95%CI: 1.07 - 2.61). CONCLUSIONS: A low prevalence of HPV positivity was observed
      in women who reside in the Tibetan Autonomous Region of China. The prevalence of
      abnormal cervical cytology and HPV type distributions were different between
      Tibetan and non-Tibetan women.

PMID- 20819534
TI  - Relationship between symptom response and esophageal pH level on standard dose of
      esomeprazole treatment for gastroesophageal reflux disease.
AB  - BACKGROUND: The relationship between symptom elimination and normalization of
      esophageal acid level of gastroesophageal reflux disease (GERD) on proton-pump
      inhibitor (PPI) therapy has been questioned. This study aimed to evaluate the
      relationship between symptom response and gastro-esophageal acidity control in
      Chinese patients with GERD on esomeprazole therapy, and to assess the role of 24
      hour esophageal pH-metry after therapy in GERD patients. METHODS: GERD patients
      with typical reflux symptoms were enrolled and received esomeprazole 40 mg once
      daily for 4 weeks. Patients with positive baseline 24-hour esophageal pH-metry
      were divided into two groups depending on an additional dual-channel 24-hour pH
      metry after treatment. The pH- group achieved normalization of esophageal pH
      level whereas the pH+ group did not. RESULTS: Of the 80 patients studied, 76 had
      abnormal baseline esophageal pH levels. Of these, 90% (52/58) of symptom-free
      patients and 67% (12/18) of symptom-persistent patients achieved esophageal pH
      normalization after therapy (P = 0.030). The mean post-therapy gastric nocturnal
      percent time of pH < 4.0 was significantly higher in pH+ group than that in pH-
      group (P < 0.001) after therapy. The multivariate regression analysis identified
      hiatus hernia (P < 0.001) and persistent reflux symptom (P = 0.004) were two
      independent factors predicting the low post-therapy esophageal pH level.
      CONCLUSIONS: Symptom elimination is not always accompanied by esophageal pH
      normalization, and vice verse. Esophageal pH-metry is recommended for GERD
      patients with hiatus hernia or with persistent reflux symptoms after PPI therapy.

PMID- 20819535
TI  - Association between four adipokines and insulin sensitivity in patients with
      obesity, type 1 or type 2 diabetes mellitus, and in the general Chinese
      population.
AB  - BACKGROUND: Hyperinsulinemic euglycemic clamp is the gold standard to evaluate
      the insulin sensitivity, but it is too complicated and expensive to use in
      clinic. We tried to find an alternative indicator to reflect insulin sensitivity.
      To evaluate the association between the four adipokines, adiponectin, leptin,
      resistin and tumor necrosis factor-alpha (TNF-alpha) with insulin sensitivity, we
      used a hyperinsulinemic euglycemic clamp to test insulin sensitivity in Chinese
      patients with obesity and type 1 or type 2 diabetes mellitus versus controls.
      METHODS: In this parallel control study, we tested insulin sensitivity using a
      hyperinsulinemic euglycemic clamp in different groups, then examined levels of
      adiponectin, leptin, resistin and TNF-alpha in serum, and the relationship
      between the different adipokines and glucose disposal rate (M value), as well as
      insulin sensitivity index (M value/insulin, M/I), which are the "gold standard"
      indices of insulin sensitivity. RESULTS: There were significant differences in
      mean leptin values in the four adipokines from the four different groups (P <
      0.001; comparison of the variation between different groups was analyzed by
      variance analysis). Compared to controls (using multiple comparison two-way
      Dunnett t test), only the leptin level showed significant differences in the four
      adipokines from the four different groups at the same time (P < 0.001). The
      association analysis between the different adipokines and M or M/I values also
      showed that only leptin negatively correlated with M (r = -0.64, P < 0.001) or
      M/I values (r = -0.56, P < 0.001); there was no relationship between the other
      three adipokines and M or M/I values. CONCLUSION: Only leptin was associated with
      M or M/I values. Therefore, leptin might be one of the predictive factors of the
      degree of insulin resistance and risk of the accompanying disease.

PMID- 20819536
TI  - Long-term prognostic value of analysis of sympathetic drive by myocardial 123I
      metaiodobenzylganidine scintigraphy in chronic heart failure.
AB  - BACKGROUND: The over increase of sympathetic drive in chronic heart failure (CHF)
      is with main responsibility for the deterioration and mortality of the disease.
      Myocardial (123)I-metaiodobenzylganidine (MIBG) scintigraphy is a non-invasive
      convenient method to assess sympathetic dysfunction in patients with CHF. The aim
      of the study was to detect if sympathetic antidrive analysed through myocardial
      MIBG scintigraphy plays a crucial role in long-term prognosis in CHF. METHODS:
      Sixty-four enrolled patients underwent myocardial MIBG scintigraphy, and their
      plasma concentration of brain natriuretic peptide (BNP), myocardial contractile
      reserve (MCR), rest left ventricular ejection fraction (rest LVEF) and New York
      Heart Association (NYHA) function class were assessed. They were separated into
      groups according to median of above parameters. Endpoint was cardiac death and it
      was recorded in each group during average 54 months' follow-up. RESULTS: At the
      end of follow-up, group with lower ratio of heart/mediastinum (H/M) had more
      death events (P = 0.001), and its BNP level was higher and MCR level was lower (P
      = 0.003 and 0.001, respectively); but its rest LVEF and NYHA function class were
      not significantly different. H/M, MCR and BNP correlated closely with death (P =
      0.000, 0.000 and 0.001, respectively). Among the three indicators the death risk
      ratio (RR) of H/M was 4.66, more than MCR and BNP (1.88 and 2.56, respectively).
      However, rest LVEF and NYHA function class did not correlate with death (P =
      0.652 and 0.384, respectively). The group with lower H/M and MCR, higher BNP had
      much more death than that with higher H/M and MCR, lower BNP, the RR being 12.8.
      CONCLUSIONS: Myocardial MIBG scintigraphy is a long-term prognostic marker in
      CHF. BNP, MCR are also excellent predictors of long-term prognosis in CHF, but
      not stronger than myocardial MIBG scintigraphy. If the three indicators were
      joined together, the prediction would become most powerful. Rest LVEF and NYHA
      have no significance in long-term prediction of CHF.

PMID- 20819537
TI  - Nifekalant hydrochloride terminating sustained ventricular tachycardia
      accompanied with QT dispersion prolongation.
AB  - BACKGROUND: Ventricular tachycardia (VT) and ventricular fibrillation are the
      main reasons causing sudden cardiac death. This study aimed to investigate the
      effects of nifekalant hydrochloride (NIF) on QT dispersion (QTd) in treating VT.
      METHODS: A total of 16 consecutive patients suffered sustained VT was included
      and then randomly divided into two groups according to the administration
      duration of NIF. In long-time group (group L), patients were injected with NIF
      continuously for at least 12 hours after a bolus dose. The patients in short-time
      group (group S) were injected with NIF just for 1 hour. RESULTS: There were 7 of
      all 10 episodes of VT which were terminated by NIF, including 4 episodes in group
      L were stopped over 1 hour after continuous infusion of NIF. One patient suffered
      from torsade de pointes. Electrocardiography analysis indicated that QTd was
      significantly decreased 12 hours after stopping of infusing NIF compared with
      that when VT stopped ((45.4 +/- 22.1) ms vs. (73.4 +/- 33.2) ms, P < 0.01), and
      the corrected QTd (QTcd) decreased too ((47.8 +/- 22.9) ms vs. (78.3 +/- 36.5)
      ms, P < 0.01). There was a positive correlation between the increase in QTd and
      dose of administrating NIF (P < 0.01), so was QTcd (P < 0.01). CONCLUSIONS: More
      administration of NIF indicates higher terminating rate of VT and more QTd
      prolongation. However, the safety is acceptable if several important issues were
      noticed in using NIF, such as serum potassium concentration, stopping side-effect
      related agents, and carefully observing clinical responses.

PMID- 20819539
TI  - Quantitative evaluation of benign meningioma and hemangiopericytoma with
      peritumoral brain edema by 64-slice CT perfusion imaging.
AB  - BACKGROUND: Hemangiopericytomas (HPCs) have a relentless tendency for local
      recurrence and metastases, differentiating between benign meningiomas and HPCs
      before surgery is important for both treatment planning and the prognosis
      appraisal. The purpose of this study was to evaluate the correlations between CT
      perfusion parameters and microvessel density (MVD) in extra-axial tumors and the
      possible role of CT perfusion imaging in preoperatively differentiating benign
      meningiomas and HPCs. METHODS: Seventeen patients with benign meningiomas and
      peritumoral edema, 12 patients with HPCs and peritumoral edema underwent 64-slice
      CT perfusion imaging pre-operation. Perfusion was calculated using the Patlak
      method. The quantitative parameters, include cerebral blood volume (CBV),
      permeability surface (PS) of parenchyma, peritumoral edema among benign
      meningiomas and HPCs were compared respectively. CBV and PS in parenchyma,
      peritumoral edema of benign meningiomas and HPCs were also compared to that of
      the contrallateral normal white matter respectively. The correlations between
      CBV, PS of tumoral parenchyma and MVD were examined. RESULTS: The value of CBV
      and PS in parenchyma of HPCs were significantly higher than that of benign
      meningiomas (P < 0.05), while the values of CBV and PS in peritumoral edema of
      benign meningiomas and HPCs were not significantly different (P > 0.05). MVD in
      parenchyma of HPCs were significantly higher than that of benign meningiomas (P <
      0.05). There were positive correlations between CBV and MVD (r = 0.648, P <
      0.05), PS and MVD (r = 0.541, P < 0.05) respectively. Furthermore, the value of
      CBV and PS in parenchyma of benign meningiomas and HPCs were significantly higher
      than that of contrallateral normal white matter (P < 0.05), the value of CBV in
      peritumoral edema of benign meningiomas and HPCs were significantly lower than
      that of contrallateral normal white matter (P < 0.05), while the value of PS in
      peritumoral edema of benign meningiomas and HPCs were not significantly different
      with that of contrallateral normal white matter (P > 0.05). CONCLUSIONS: CT
      perfusion imaging can provide critical information on the vascularity of HPC and
      benign meningiomas. Determination of maximal CBV and corresponding PS values in
      the parenchyma may be useful in the preoperative differentiating HPC from benign
      meningiomas.

PMID- 20819538
TI  - Expression of CD123 and CD114 on the bone marrow cells of patients with
      myelodysplastic syndrome.
AB  - BACKGROUND: Recent studies have shown that interleukin-3 receptor alpha (CD123)
      is highly expressed on leukemia stem cells of patients with acute myeloid
      leukemia, and is correlated with tumor load and poor prognosis. The expression of
      CD123 may also be high in patients with myelodysplastic syndrome (MDS). In this
      study, the expression and clinical significance of CD123 and granulocyte colony
      stimulating factor (G-CSF) receptor (CD114) on the bone marrow cells of patients
      with MDS were investigated to explore the molecular marker of the malignant clone
      of MDS. METHODS: Forty-two patients with MDS, who were diagnosed in the
      Hematological Department of General Hospital of Tianjin Medical University from
      2008 to 2009, and twelve normal controls were enrolled in this study.
      Fluorescence activiated cell sorter (FACS) was used to measure the expression of
      CD123 on CD34(+)CD38(-) cells and CD114 on CD34(+) cells of the bone marrow of
      these patients and controls and the clinical significance was analyzed. The
      expression of CD114 on CD123(+)CD34(+)CD38(-) cells was further measured to
      explore the molecular marker of the malignant clone in MDS. RESULTS: MDS patients
      displayed significantly higher proportion of CD34(+)CD38(-)/CD34(+) ((14.03 +/-
      5.27)%) than normal controls ((7.70 +/- 4.36)%, P < 0.05). The expression rate of
      CD123(+)CD34(+)CD38(-)/CD34(+)CD38(-) was significantly higher in MDS patients
      ((48.39 +/- 28.15)%) than that in normal controls ((8.75 +/- 11.71)%, P < 0.01).
      The expression level of CD123 was significantly correlated with the proportion of
      bone marrow blasts (r = 0.457, P < 0.05). The expression rate of
      CD114(+)CD34(+)/CD34(+) was lower in MDS patients ((33.05 +/- 21.71)%) than that
      in normal controls ((38.99 +/- 19.07)%) but was not statistically significant (P
      > 0.05). The expression of CD114 on CD123(+)CD34(+)CD38(-) cells ((34.82 +/-
      29.58)%) was significantly lower than that on CD123(-)CD34(+)CD38(-) cells
      ((53.48 +/- 27.41)%) of MDS patients (P < 0.05). CONCLUSIONS: MDS patients
      displayed higher proportion of CD34(+)CD38(-)/CD34(+) than normal controls. CD123
      was highly expressed in the bone marrow of the patients with MDS, significantly
      correlated with the proportion of bone marrow blasts, and thus might be the
      marker of MDS malignant clone. CD123(+)CD34(+)CD38(-) cells exhibited lower
      expression of G-CSF receptors, which might partly explain why MDS clone responds
      worse to G-CSF in vitro and in vivo.

PMID- 20819540
TI  - Diagnostic capability of Fourier-Domain optical coherence tomography in early
      primary open angle glaucoma.
AB  - BACKGROUND: Optical coherence tomography (OCT) is a high resolution noncontact
      imaging modality which can quantitatively detect the optic disc and retinal
      structure. This study was designed to evaluate the diagnostic capability of
      parameters of the optic disc, retinal nerve fiber layer thickness, and ganglion
      cell complex (GCC) using a new technology called Fourier-domain OCT (FD-OCT) for
      early primary open angle glaucoma (POAG) patients. METHODS: Two groups of
      patients, early perimetric damage POAG and normal subjects were included in this
      observational cross-sectional study. All patients underwent FD-OCT and visual
      field examination in addition to full ophthalmic examinations. Receiver operating
      characteristic curves (ROC) were studied for all parameters. The sensitivity and
      specificity for distinguishing between normal and early glaucomatous eyes, the
      areas under the receiver operating characteristic curves (AROC) and positive,
      negative likelihood ratios were evaluated for all the single parameters and
      selected combined parameters using arbitrary cutoffs. RESULTS: Thirty-four eyes
      of 34 early POAG patients and 42 eyes of 42 normal subjects were analyzed.
      Cup/disc (C/D) vertical ratio presented the best sensitivity and positive
      likelihood ratio for selected specificities (95% and 85%) which were 79.4% and
      88.2%, 33.4 and 7.4, respectively. Among all single parameters, the C/D vertical
      ratio demonstrated the highest AROC which was at 0.930. The average thickness of
      circumpapillary RNFL on 3.45 mm showed the highest AROC among all of the
      peripapillary RNFL parameters. The sensitivity at selected specificity and AROC
      of GCC were not as high as C/D vertical ratio and RNFL AT on 3.45 mm. When the
      C/D vertical ratio, RNFL AT on 3.45 mm, and rim area were combined using a
      logistical diagnostic model, the AROC was raised to 0.949 but not significantly
      different from the top single parameter, C/D vertical ratio. CONCLUSIONS: The key
      parameters obtained by FD-OCT were able to show the significant differences of
      optic discs, thickness of RNFL and GCC between POAG patients and normal subjects.
      According to sensitivity, specificity, likelihood ratio and AROC, the top three
      parameters from FD-OCT for early diagnosis of POAG were C/D vertical ratio, RNFL
      AT on 3.45 mm, and the rim area.

PMID- 20819542
TI  - Epidemiologic study of soft tissue rheumatism in Shantou and Taiyuan, China.
AB  - BACKGROUND: Soft tissue rheumatism is a group of common rheumatic disorders
      reported in many countries. For investigating the prevalence rate of soft tissue
      rheumatism in different population in China, we carried out a population study in
      Shantou rural and Taiyuan urban area. METHODS: Samples of 3915 adults in an urban
      area of Taiyuan, Shanxi Province, and 2350 in a rural area of Shantou, Guangdong
      Province were surveyed. Modified International League of Association for
      Rheumatology (ILAR)-Asia Pacific League of Association for Rheumatology (APLAR)
      Community Oriented Program for Control of Rheumatic Diseases (COPCORD) core
      questionnaire was implemented as screening tool. The positive responders were
      then all examined by rheumatologists. RESULTS: Prevalence rate of soft tissue
      rheumatism was 2.0% in Taiyuan, and 5.3% in Shantou. Rotator cuff (shoulder)
      tendinitis, adhesive capsulitis (frozen shoulder), lateral epicondylitis (tennis
      elbow), and digital flexor tenosynovitis (trigger finger) were the commonly seen
      soft tissue rheumatism in both areas. Tatarsalgia, plantar fasciitis, and De
      Quervain's tenosynovitis were more commonly seen in Shantou than that in Taiyuan.
      Only 1 case of fibromyalgia was found in Taiyuan and 2 cases in Shantou. The
      prevalence of soft tissue rheumatism varied with age, sex and occupation.
      CONCLUSIONS: Soft tissue rheumatism is common in Taiyuan and Shantou, China. The
      prevalence of soft tissue rheumatism was quite different with different
      geographic, environmental, and socioeconomic conditions; and varying with age,
      sex, and occupation. The prevalence of fibromyalgia is low in the present survey.

PMID- 20819541
TI  - Directed shift of vaginal flora after topical application of sucrose gel in a
      phase III clinical trial: a novel treatment for bacterial vaginosis.
AB  - BACKGROUND: Bacterial vaginosis (BV) is one of the most common infectious
      diseases among sexually active women and is associated with the increased
      acquisition of a variety of sexually transmitted diseases. This study aimed to
      compare the efficacy of a non-antibiotic sucrose gel against an antibiotic
      metronidazole gel for the treatment of BV. METHODS: A randomized, double-blinded,
      multi-center, parallel-group, placebo-controlled phase III clinical trial was
      conducted at eight hospitals in China. A total of 560 subjects with clinically
      diagnosed BV were randomly assigned into three groups for vaginally receiving
      sucrose, metronidazole, and placebo gels, respectively, twice daily for five
      consecutive days. The efficacy of therapeutic cure, defined as an achievement of
      both microbiologic cure (a Nugent score of 3 or less) and clinical cure (a
      resolution of the clinical findings from the baseline visit), was evaluated at
      the 1st and 2nd test-of-cure (TOC) visits at 7-10 and 21-35 days after the start
      of treatment, respectively. RESULTS: Therapeutic cure rates for sucrose,
      metronidazole, and placebo gel groups were 83.13%, 71.30% and 0.92%, at the 1st
      TOC, and 61.04%, 66.67% and 7.34%, at the 2nd TOC, respectively. While there was
      no significant difference between the sucrose and metronidazole gel groups at the
      2nd TOC (P = 0.305), and sucrose gel was more effective than metronidazole gel at
      the 1st TOC (P = 0.009). CONCLUSION: These findings suggest that sucrose gel
      restores normal vaginal flora more rapidly than metronidazole gel and can be used
      as a novel treatment for BV.

PMID- 20819543
TI  - Association between painful physical symptoms and clinical outcomes in Chinese
      patients with major depressive disorder: a three-month observational study.
AB  - BACKGROUND: Painful physical symptoms (PPS) may present as a component of major
      depressive disorder (MDD). Their effect in Chinese patients has not been
      investigated. This analysis reports the changes in disease severity, treatment
      patterns, quality of life and outcomes in a Chinese cohort according to the
      presence (PPS+) or absence (PPS-) of painful physical symptoms. METHODS: A
      subgroup of Chinese patients from a large observational 3-month study of patients
      from Asian countries and regions of China were classified using the modified
      Somatic Symptom Inventory (SSI) as PPS+ (mean score >or= 2) or PPS- (mean score <
      2). Depression severity was assessed with the Clinical Global Impression of
      Severity (CGI-S) scale and 17-item Hamilton depression rating scale (HAMD(17)).
      Pain severity was measured using a visual analogue scale (VAS), while the EuroQoL
      (EQ-5D) assessed patient well-being. Antidepressants were compared with regard to
      their efficacy. RESULTS: Of the 299 Chinese patients enrolled in the study, 105
      were classified as PPS+ (73/105, 70% women). At baseline, PPS+ patients reported
      greater pain severity (VAS, mean (SD): 49.56 (26.49) vs. 16.60 (20.99) for PPS-,
      P < 0.01), were more depressed (HAMD(17), mean (SD): 25.32 (5.47) vs. 23.33
      (5.24) for PPS-, P = 0.002) and had poorer quality of life (EQ-5D Health State,
      mean (SD): 38.48 (22.38) vs. 49.57 (18.54) for PPS-, P < 0.001). PPS+ patients
      showed less overall improvement in depressive symptom severity (HAMD(17), change
      from baseline (95%CI): -17.38 (-18.65, -16.12) vs. -19.20 (-20.05, -18.35) for
      PPS-, P = 0.032; CGI-S, change from baseline (95%CI): -2.85 (-3.11, -2.58) vs. 
      3.20 (-3.38, -3.02) for PPS-, P = 0.044). CONCLUSIONS: PPS were less frequent
      than expected compared with previous studies of Asian populations. PPS+ were
      associated with greater MDD severity and less improvement than PPS- when
      antidepressants were given.

PMID- 20819544
TI  - Adenovirus-mediated and tumor-specific transgene expression of the sodium-iodide
      symporter from the human telomerase reverse transcriptase promoter enhances
      killing of lung cancer cell line in vitro.
AB  - BACKGROUND: The sodium-iodide symporter (NIS) protein can mediate the active
      radioiodine uptake. The human telomerase reverse transcriptase (hTERT) promoter
      is known to be selectively reactivated in majority of tumors and hence could be
      used for tumor targeting. We constructed a recombinant adenovirus containing the
      human sodium iodide symporter (hNIS) gene directed by the hTERT promoter,
      characterized the ability of infected cells in uptaking iodide, and explored the
      therapeutic efficacy of (131)I in a lung cancer cell line in vitro. METHODS: The
      hTERT promoter was amplified by PCR from DNA isolated from log-phase HepG2 cells,
      subcloned into lineralized FL*-hNIS/pcDNA3, and then the hTERT-hNIS sequence was
      subcloned into the shuttle plasmid pAdTrack. The recombinant adenovirus Ad-hTERT
      hNIS was constructed by AdEasy system. A positive control adenovirus Ad-CMV-hNIS
      and a negative control adenovirus Ad-CMV were created similarly. A549 cells were
      transduced with recombinant adenoviruses. (125)I uptake studies and sodium
      perchlorate suppression studies were used to confirm hNIS expression and
      function. Toxic effects of (131)I on tumor cells were studied by in vitro
      clonogenic assay. RESULTS: We first successfully constructed an adenovirus
      mediated transgene expression system of the hNIS under the control of hTERT
      promoter. When infected with recombinant adenovirus constructs expressing hNIS
      directed by hTERT- and CMV-promoters (Ad-hTERT-hNIS and Ad-CMV-hNIS,
      respectively), the lung cancer cell line A549 had increased ability to uptake
      radioiodide up to 23- and 30-fold compared to the control parental cells,
      respectively. The radioiodide uptake ability of both the Ad-CMV-hNIS and Ad-hTERT
      hNIS transduced cell lines were repressed 11-fold by sodium perchlorate (NaClO4).
      The subsequent in vitro clonogenic assay of the infected A549 cell line was
      further repressed to 23% (Ad-CMV-hNIS) and 30% (Ad-hTERT-hNIS) of the control
      group after receiving radioiodide for 7 hours (P < 0.001). CONCLUSION: Our
      preliminary study indicates that an adenovirus mediated transgene expression
      system of the hNIS under the control of hTERT promoter has the potential to
      become an effective wide-spectrum yet highly specific anti-cancer strategy.

PMID- 20819545
TI  - Expression of thrombin and its associated protein in cerebellum of human and rat
      after intracerebral hemorrhage.
AB  - BACKGROUND: Intracerebral hemorrhage (ICH) can cause brain damage through a
      number of pathways. The purpose of the study was to explore the effect of
      thrombin, protease nexin-1 (PN-1) and protease activated receptor-1 (PAR-1) in
      rat and human cerebellum after ICH. METHODS: A model of ICH was produced in adult
      Sprague-Dawley rats by direct injection of autologous blood (50 microl) into
      caudate nucleus. Patients with injured hemorrhage were also enrolled in this
      study. Different expressions of thrombin, PAR-1, PN-1 were detected in rat and
      human cerebellum by immunohistochemistry and in situ hybridization. RESULTS: In
      rat cerebellum, thrombin protein significantly increased at 6 hours and reached
      the maximum 2 days after ICH. The expression of PAR-1 protein reached the maximum
      at 24 - 48 hours, and then began to decrease. The expression of PN-1 protein
      reached the maximum at 3 hours, decreased somewhat after that and increased a
      little at 5 days after ICH. While in human cerebellum, the changing tendency of
      thrombin, PAR-1 and PN-1 was almost conform to the rat. CONCLUSION: In
      cerebellum, thrombin can activate PAR-1 expression after ICH, and PN-1 appears
      quickly after ICH in order to control the deleterious effect of thrombin.

PMID- 20819546
TI  - Combined expression of CTGF and tissue inhibitor of metalloprotease-1 promotes
      synthesis of proteoglycan and collagen type II in rhesus monkey lumbar
      intervertebral disc cells in vitro.
AB  - BACKGROUND: Low back pain has emerged as a widespread disease often caused by
      intervertebral disc degeneration. This study aimed to establish an in vitro cell
      culture model of rhesus monkey lumbar intervertebral discs and to investigate the
      effect of combined connective tissue growth factor (CTGF) and tissue inhibitor of
      metalloprotease-1 (TIMP-1) expression mediated by adeno-associated virus (AAV) on
      collagen type II and proteoglycan levels. The purpose of these investigations was
      to explore potential methods for relieving the degeneration of lumbar
      intervertebral disc cells. METHODS: Rhesus monkey lumbar intervertebral disc
      nucleus pulposus cells (NPCs) were isolated by enzyme digestion, cultured, and
      transduced with rAAV2-CTGF-IRES-TIMP-1, rAAV2-CTGF, or rAAV2-TIMP-1 at a
      multiplicity of infection (MOI) of 10(6). The expression of collagen type II and
      proteoglycan was measured using RT-PCR and Western blotting. The synthetic rate
      of proteoglycan was measured using (35)S incorporation. RESULTS: Rhesus monkey
      lumbar intervertebral disc NPCs were transduced with rAAV2-CTGF-IRES-TIMP-1,
      rAAV2-CTGF, and rAAV2-TIMP-1 and the transduced genes were expressed and
      detected. Compared to the control, CTGF promoted the synthesis of collagen type
      II and proteoglycan. TIMP-1 showed an enhancing effect on the expression of
      proteoglycan but no effect on collagen type II. Expression of both genes in
      rhesus monkey lumbar intervertebral disc NPCs significantly enhances the
      synthesis of proteoglycan and collagen type II. CONCLUSIONS: Single gene
      transduction of CTGF or TIMP-1 can enhanced synthesis of proteoglycan. CTGF
      expression can also enhance collagen type II protein synthesis. Combined
      transduction of both CTGF and TIMP1 can significantly promote the expression of
      proteoglycan and collagen type II to levels greater than transduction of a single
      gene alone. Our study provides a good basis for multi-gene therapy to treat
      lumbar intervertebral disc degeneration.

PMID- 20819547
TI  - Effect of partial liquid ventilation on oleic acid-induced inflammatory responses
      in piglets.
AB  - BACKGROUND: Pediatric patients are susceptible to lung injury. Acute lung injury
      (ALI) in children often results in a high mortality. Partial liquid ventilation
      (PLV) has been shown to markedly improve oxygenation and reduce histologic
      evidence of injury in a number of lung injury models. This study aimed to examine
      the hypothesis that PLV would attenuate the production of local and systemic
      cytokines in an immature piglet model of ALI induced by oleic acid (OA). METHODS:
      Twelve Chinese immature piglets were induced to develop ALI by oleic acid. The
      animals were randomly assigned to two groups (n = 6): (1) conventional mechanical
      ventilation (MV) group and (2) PLV with FC-77 (10 ml/kg) group. RESULTS: Compared
      with MV group, PLV group got better cardiopulmonary variables (P < 0.05). These
      variables included heart rate, mean blood pressure, blood pH, partial pressure of
      arterial oxygen (PaO2), PaO2/FiO2 and partial pressure of arterial carbon dioxide
      (PaCO2). Partial liquid ventilation reduced IL-1beta, IL-6, IL-10 and TNF-alpha
      both in plasma and tissue concentrations compared with MV group (P < 0.05).
      CONCLUSIONS: Partial liquid ventilation provides protective effects against
      inflammatory responses in the lungs of oleic acid-induced immature piglets.

PMID- 20819548
TI  - Effects of 5-hydroxytryptamine and 5-hydroxytryptamine 2A/2C agonist on the
      genioglossus activity and sleep apnea in rats.
AB  - BACKGROUND: 5-Hydroxytryptamine (5-HT) is a common neurotransmitter in the brain
      which plays an important role in the pathogenesis of sleep apnea. Dysfunction of
      5-HT and 5-HT(2) receptors may lead to the collapse of the upper airway and the
      instability of respiratory control, which in turn produce apnea. Genioglossus
      (GG) is one of the most important oropharyngeal muscles maintaining the upper
      airway open. The present study aimed to investigate the effects of 5-HT and 5
      HT(2) receptor on GG activity and the sleep apnea in Sprague-Dawley (SD) rats.
      METHODS: Microinjection probes were placed within the fourth ventricle of sixteen
      SD rats. After recovery for a week, the electromyogram (EMG) of GG was recorded
      in the anesthetized and vagotomized rats. The changes of GG activity before and
      after the microinjection of 5-HT or 5-HT(2A/2C) agonist -2,5-dimethoxy-4
      iodoamphetamine hydrochloride (DOI) were observed. Probes were also laid in
      another eight SD rats. Electroencephalogram (EEG), EMG of neck muscle and
      respiration were recorded at the same time a week later. The effects of DOI on
      the occurrence of sleep apnea were explored. RESULTS: Both 5-HT and DOI
      significantly enhanced the activity of GG just 3 minutes after the completion of
      injection. The effect of 5-HT disappeared quickly and the effect of DOI lasted
      for more than 27 minutes. DOI also significantly decreased the post-sigh apnea
      index in non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep and
      decreased the spontaneous apnea index only in NREM sleep (P < 0.05,
      respectively). CONCLUSION: 5-HT and 5-HT(2A/2C) system correlated closely with
      the pathogenesis of the sleep apnea syndrome and 5-HT receptors may become the
      target of the drug treatment.

PMID- 20819549
TI  - Effect of house dust mite immunotherapy on interleukin-10-secreting regulatory T
      cells in asthmatic children.
AB  - BACKGROUND: Subcutaneous specific immunotherapy has been demonstrated to be
      capable of inducing T-cell regulatory response. Interleukin-10 (IL-10) plays a
      crucial role in inducing allergen-specific tolerance. However the reports of the
      changes of IL-10 in house dust mite (HDM)-specific immunotherapy were varied. The
      aim of this study was to evaluate the function of IL-10-secreting regulatory T
      cells in asthma children successfully treated with HDM immunotherapy. METHODS:
      Peripheral blood mononuclear cells (PBMCs) were isolated from 27 patients
      following 1.5 - 2 years of HDM-specific immunotherapy (SIT, SIT group) and from
      27 matched treated asthmatic children allergic to HDM (asthma group). After 48
      hours of in vitro stimulation with HDM extracts, IL-10-secreting regulatory T
      cells were measured by four colour flow cytometry. Sera were tested for allergen
      specific IgG(4) and IgE using the Immuno CAP 100 assay. RESULTS: PBMCs from
      children undergoing immunotherapy following HDM extracts stimuli produced
      significantly more IL-10 compared with the asthma group. The frequency of iTreg
      cells and aTreg cells increased in SIT group after HDM stimulation, while it was
      not affected in the asthma group. Among the iTreg cells and aTreg cells, the
      frequency of CD4(+)CD25(-)Foxp3(-)IL-10(+) Treg cells increased the most which
      was 2 times higher than that in unstimulated cultures in SIT group. The levels of
      HDM-specific IgG(4) of SIT group was significiently higher compared with asthma
      group, but there was no correlation of the levels of HDM-specific IgG(4) and IL
      10 secreting Treg cells. CONCLUSIONS: HDM-specific immunotherapy can successfully
      upregulate the frequency of IL-10-secreting Treg cells. CD4(+)CD25(-)Foxp3(-)IL
      10(+) Treg cells may play a key role in inducing the immune tolerance in HDM
      specific immunotherapy.

PMID- 20819550
TI  - Determination of drug concentration in aqueous humor of cataract patients
      administered gatifloxacin ophthalmic gel.
AB  - BACKGROUND: Ophthalmic gel has been developed to increase the drug concentration
      in aqueous humor and to retard the loss of drug from the conjunctival sac. The
      research was to compare the drug concentration in aqueous humor of cataract
      patients administered 0.3% gatifloxacin ophthalmic gel with that in patients
      administered 0.3% gatifloxacin ophthalmic solution. METHODS: Ninety-six patients
      with cataract (96 eyes) were randomly assigned to 8 groups. The patients in
      groups 1-4 received topical gatifloxacin 0.3% ophthalmic gel and those in groups
      5-8 received gatifloxacin 0.3% ophthalmic solution. The dose regimen was 1 drop,
      4 times a day for 3 consecutive days prior to cataract surgery. On the day of
      surgery, 1 drop was applied at 15, 30, 60 or 120 minutes before commencement of
      cataract surgery in groups 1 and 5, groups 2 and 6, groups 3 and 7, and groups 4
      and 8, respectively. Aqueous humor was extracted during the cataract surgery for
      the analysis of gatifloxacin concentration.. RESULTS: The concentrations of
      gatifloxacin in aqueous humor were (0.24 +/- 0.25) microg/ml, (1.11 +/- 0.74)
      microg/ml, (2.32 +/- 2.01) microg/ml and (1.85 +/- 1.14) microg/ml in groups 1 to
      4, and (0.16 +/- 0.25) microg/ml, (0.31 +/- 0.24) microg/ml, (0.75 +/- 0.28)
      microg/ml and (0.33 +/- 0.22) microg/ml in groups 5 to 8, respectively. Patients
      receiving gatifloxacin ophthalmic gel showed greater mean values of gatifloxacin
      concentration in aqueous humor than those receiving gatifloxacin solution, and
      such differences were significant with P < 0.05 for all comparisons except that
      between groups 1 and 5. CONCLUSION: Topical gatifloxacin ophthalmic gel can
      attain significantly greater drug concentrations in human aqueous humor than
      gatifloxacin ophthalmic solution.

PMID- 20819551
TI  - Efficacy and tolerability of one-site versus two-site phaco-trabeculectomy: a
      meta-analysis of randomized controlled clinical trials.
AB  - BACKGROUND: Phacotrabeculectomy can be performed using one-site or two-site
      incisions. This meta-analysis evaluated the efficacy and tolerability of one-site
      versus two-site phacotrabeculectomy in the treatment of patients with coexisting
      cataract and glaucoma. METHODS: A comprehensive literature search was performed
      according to the Cochrane Collaboration methodology to identify randomized
      controlled clinical trials comparing one-site with two-site phacotrabeculectomy.
      Studies meeting our predefined criteria were included in the meta-analysis.
      Efficacy estimates were measured by weighted mean difference (WMD) for the
      percentage intraocular pressure (IOP) reduction from baseline to end point,
      relative risk (RR) for the proportion of patients with a best-corrected visual
      acuity (BCVA) of 0.5 or better after surgery and complete success rates.
      Tolerability estimates were measured by RR for adverse events. All of outcomes
      were reported with 95% confidence interval (95%CI). Data were synthesised by
      Stata 10.1 for Windows. RESULTS: Two-site phacotrabeculectomy was associated with
      greater reductions in IOP than the one-site procedure (WMD: -5.99, 95%CI: -10.74 
      -1.24, P = 0.01). A greater proportion of patients also achieved a BCVA of 0.5
      or better (RR: 0.91, 95%CI: 0.74 - 1.12, P = 0.36) and the target IOP without
      anti-glaucoma medication at the study end point (RR: 0.94, 95%CI: 0.83 - 1.07, P
      = 0.34) after two-site than one-site phacotrabeculectomy, but the differences
      were not significant. There were no significant differences in adverse events
      between two surgical procedures. CONCLUSIONS: Two-site phacotrabeculectomy is
      superior to one-site phacotrabeculectomy in reducing IOP, but other post
      operative effects are similar. One-site and two-site phacotrabeculectomies have
      similar adverse event rates.

PMID- 20819552
TI  - Vascular surgery and diabetic foot revascularization.

PMID- 20819554
TI  - Heme oxygenase-1 is the candidate targeting for organ transplantation.
AB  - OBJECTIVE: To review the role of heme oxyenase-1 in organ transplantation and
      explore the potential applications targeted on overexpression of heme oxyenase-1
      gene. DATA SOURCES: The data cited in this review were mainly obtained from the
      articles listed in Medline and PubMed, published from January 1996 to December
      2008. The search terms were "heme oxygenase-1" and "transplantation". STUDY
      SELECTION: Articles regarding the role of heme oxyenase-1 in organ
      transplantation and its protective role in transplants were selected. Protective
      effects of heme oxygenase-1 overexpression using a gene transfer approach against
      ischaemic reperfusion injury during transplantation were widely explored.
      RESULTS: Local heme oxygenase-1 overexpression in the graft ameliorates the
      ischaemic reperfusion injury. This is due to removal of heme, a potent prooxidant
      and proinflammatory agent, but also because of generation of biologically active
      products. CONCLUSIONS: Overexpressive heme oxygenase-1 activity is associated
      with tissue protection in the setting of graft, ischaemic reperfusion injury.
      Gene therapy is attractive to us; but a long way from general application. In
      terms of heme oxygenase-1, the gene promoters are polymorphic. Although
      individualization is an important principle during clinical application, it is
      difficult to put into practice.

PMID- 20819553
TI  - Dynamic mathematical models of HIV/AIDS transmission in China.

PMID- 20819555
TI  - Pancreatic fistula may be an important complication following spleen-preserving
      radical gastrectomy with dissection of No. 10 and No. 11 lymph nodes.

PMID- 20819556
TI  - Mediastinoscopy after stent implantation: a good method for diagnosis and
      treatment of severe superior vena cava syndrome.

PMID- 20819557
TI  - Totally laparoscopic Roux-en-Y cystojejunostomy as a sole treatment option for
      pancreatic pseudocysts: a report of four cases.

PMID- 20819558
TI  - Intravitreal bevacizumab injection for chronic central serous chorioretinopathy.

PMID- 20819559
TI  - Laparoscopic lysis of duodenum for superior mesenteric artery syndrome: how and
      why we do it?

PMID- 20819560
TI  - Is radiofrequency ablation justified for liver metastatic VIPoma patient
      undergoing Whipple procedure?

PMID- 20819561
TI  - Primitive neuroectodermal tumor of the kidney with inferior vena cava tumor
      thrombus during pregnancy response to sorafenib.

PMID- 20819562
TI  - A jejunopericardial fistula 14 years after surgery for gastric cancer.

PMID- 20819563
TI  - Influence of granulocyte colony-stimulating factor on cardiac function in
      patients with acute myocardial infarction and leukopenia after revascularization.
AB  - BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) seems to improve
      cardiac function and perfusion when used systemically through mobilization of
      stem cells into peripheral blood, but results of previous clinical trials remain
      controversial. This study was designed to investigate safety and efficacy of
      subcutaneous injection of G-CSF on left ventricular function in patients with
      impaired left ventricular function after ST-segment elevation myocardial
      infarction (STEMI). METHODS: Thirty-three patients (22 men; age, (68.5 +/- 6.1)
      years) with STEMI and with comorbidity of leukopenia were included after
      successful primary percutaneous coronary intervention within 12 hours after
      symptom onset. Patients were randomized into G-CSF group who received G-CSF (10
      microg/kg of body weight, daily) for continuous 7 days and control group. Results
      of blood analyses, echocardiography and angiography were documented as well as
      possibly occurred adverse events. RESULTS: No severe adverse events occurred in
      both groups. Mean segmental wall thickening in infract segments increased
      significantly at 6-month follow up compared with baseline in both groups, but the
      longitudinal variation between two groups had no significant difference (P >
      0.05). The same change could also be found in longitudinal variation of wall
      motion score index of infarct segments (P > 0.05). At 6-month follow-up, left
      ventricular end-diastolic volume of both groups increased to a greater extent,
      but there were no significant differences between the two groups when comparing
      the longitudinal variations (P > 0.05). In both groups, left ventricular ejection
      fraction measured by echocardiography ameliorated significantly at 6-month follow
      up (P < 0.05), but difference of the longitudinal variation between two groups
      was not significant (P > 0.05). When pay attention to left ventricular ejection
      fraction measured by angiocardiography, difference of the longitudinal variation
      between groups was significant (P = 0.046). Early diastolic mitral flow velocity
      deceleration time changed significantly at 6- month follow-up in both groups (P =
      0.05). CONCLUSIONS: Mobilization of stem cells by G-CSF after reperfusion of
      infarct myocardium is safe and seems to offer a pragmatic strategy for recovery
      of myocardial global function.

PMID- 20819564
TI  - Attenuation of tumor necrosis factor-alpha elevation and improved heart function
      by postconditioning for 60 seconds in patients with acute myocardial infarction.
AB  - BACKGROUND: Postconditioning has been shown to reduce infarct size,
      ischemic/reperfusion injury and myocardial injury in patients with acute
      myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI).
      This study tested the hypothesis that postconditioning attenuates the elevation
      of tumor necrosis factor-alpha (TNF-alpha) and improves heart function in
      patients with AMI after PCI. METHODS: A total of 75 patients were randomly
      assigned to 1 of 3 groups: the routine group (n = 26), in which no intervention
      was given at the onset of reperfusion; and the Postcon-30s (n = 25) or Postcon-60
      s (n = 24) groups, in which 3 cycles of 30- or 60-second balloon deflation and
      inflation were repetitively performed. TNF-alpha serum concentration was measured
      by ELISA. Global and regional left ventricular systolic function was determined
      by echocardiography at 1 year. Thirty-four normal controls (NC) were enrolled in
      the study. RESULTS: The TNF-alpha concentration in patients with AMI was
      significantly elevated at baseline compared to controls (P < 0.01). Concentration
      levels increased in the routine and Postcon-30s, but not in Postcon-60s group at
      7 days (P < 0.05). As for linear associations among the three groups, left
      ventricular ejection fraction (LVEF) and wall motion score index (WMSI) were
      ranked as follows: Postcon-60s > Postcon-30s > routine (P values all < 0.05, 65%
      vs. 57% vs. 52% and 1.10 vs. 1.27 vs. 1.53) after 1 year. More importantly, there
      was a significant relevance between the soluble TNF-alpha serum concentration at
      7 days and LVEF or WMSI after 1 year (P values all < 0.0001). CONCLUSIONS:
      Postconditioning, in particular Postcon-60s was associated with long-term
      cardioprotective effects for inhibition of the inflammatory response and
      reperfusion injury. The soluble TNF-alpha serum concentration provided powerful
      prognostic information of global and regional left ventricular systolic function
      in patients with AMI.

PMID- 20819565
TI  - Impact of patients' symptom interpretation on care-seeking behaviors of patients
      with acute myocardial infarction.
AB  - BACKGROUND: Delay in seeking medical care in patients with acute myocardial
      infarction (AMI) is receiving increasing attention. This study aimed to examine
      the association between expected symptoms and experienced symptoms of AMI and its
      effects on care-seeking behaviors of patients with AMI. METHODS: Between November
      1, 2005 and December 31, 2006, a cross-sectional and multicenter survey was
      conducted in 19 hospitals in Beijing and included 799 patients with ST-elevation
      myocardial infarction (STEMI) admitted within 24 hours after onset of symptoms.
      Data were collected by structured interviews and medical record review. RESULTS:
      The median (25%, 75%) prehospital delay was 140 (75, 300) minutes. Only 264
      (33.0%) arrived at the hospital by ambulance. The most common symptoms expected
      by patients with STEMI were central or left chest pain (71.4%), radiating arm or
      shoulder pain (68.7%), shortness of breath or dyspnea (65.5%), and loss of
      consciousness (52.1%). The most common symptoms experienced were central or left
      chest pain (82.1%), sweats (71.8%), shortness of breath or dyspnea (43.7%),
      nausea or vomiting (32.3%), and radiating pain (29.4%). A mismatch between
      symptoms experienced and those expected occurred in 41.8% of patients. Patients
      who interpreted their symptoms as noncardiac in origin were more likely to arrive
      at the hospital by self-transport (86.5% vs. 52.9%, P < 0.001) and had longer
      prehospital delays (medians, 180 vs. 120 minutes, P < 0.001) compared to those
      who interpreted their symptoms as cardiac in origin. CONCLUSIONS: Symptom
      interpretation influenced the care-seeking behaviors of patients with STEMI in
      Beijing. A mismatch between expectation and actual symptoms was associated with
      longer prehospital delay and decreased use of emergency medical service (EMS).

PMID- 20819566
TI  - Predictive validity of BODE index for anxious and depressive symptoms in patients
      with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Anxiety and depression are two of the commonest and most modifiable
      comorbidities of chronic obstructive pulmonary disease (COPD) and have an
      independent effect on health and prognosis. FEV1% has been shown to be a poor
      predictor of anxiety and depression. The body mass index, degree of airflow
      obstruction, dyspnea, and exercise capacity (BODE) index is a multidimensional
      assessment system which may predict health outcome in COPD patients. The purpose
      of this study was to investigate the predictive validity of the BODE index for
      anxious and depressive symptoms in COPD patients. METHODS: This was a multicenter
      prospective cross-sectional study in 256 patients with stable COPD. Anxious and
      depressive symptoms were assessed using the Hospital Anxiety and Depression Scale
      (HADS). The relationships between anxiety, depression and potential predictors
      (including the BODE index) were analyzed by a binary Logistic regression model.
      RESULTS: Subjects who were anxious and depressive walked a shorter six-minute
      walking distance (6MWD), had more dyspnea, a higher BODE index, and lower health
      related quality of life (P < 0.01). Anxiety and depression score was
      significantly correlated with BODE index, respectively (r = 0.335, P < 0.001; r =
      0.306, P < 0.001). The prevalence of anxiety and depression increased with BODE
      stage increasing (P < 0.05). On the basis of binary Logistic regression, the BODE
      index was a good and independent predictor of anxiety and depression because it
      comprised dyspnea and 6MWD, which were shown to be the main determinants.
      CONCLUSIONS: The predictive validity of the BODE index for anxiety and depression
      was demonstrated. We propose that the BODE index should be included in assessment
      of COPD severity.

PMID- 20819567
TI  - The association between common genetic variation in the FTO gene and metabolic
      syndrome in Han Chinese.
AB  - BACKGROUND: Genome-wide association studies for type 2 diabetes mellitus (T2DM)
      identified FTO gene as a locus conferring increased risk for common obesity in
      many populations with European ancestry. However, the involvement of FTO gene in
      obesity or T2DM related metabolic traits has not been consistently established in
      Chinese populations. The objective of this study was to investigate the
      association of FTO genetic polymorphisms with metabolic syndrome (MetS) in Han
      Chinese. METHODS: We tested 41 FTO single nucleotide polymorphisms (SNPs) for
      association between FTO and MetS-related traits. There were a total of 236
      unrelated subjects (108 cases and 128 controls), grouped according to the
      International Diabetes Federation (IDF) criteria. RESULTS: Of the 41 SNPs
      examined, only SNP rs8047395 exhibited statistical significance (P = 0.026) under
      a recessive model, after Bonferroni adjustment for multiple testing (OR 1.64,
      95%CI 1.11-2.42; P = 0.014). The common distributions of this polymorphism among
      Chinese--with a minor allele frequency (MAF) of 36% in the control group versus
      48% in the MetS group--greatly improved our test power in a relatively small
      sample size for an association study. Previously identified obesity- (or T2DM-)
      associated FTO SNPs were less common in Han Chinese and were not associated with
      MetS in this study. No significant associations were found between our FTO SNPs
      and any endophenotypes of MetS. CONCLUSIONS: A more common risk-conferring
      variant of FTO for MetS was identified in Han Chinese. Our study substantiated
      that genetic variations in FTO locus are involved in the pathogenesis of MetS.

PMID- 20819568
TI  - Evaluation and clinical application of a new method for detecting ADAMTS13
      activity.
AB  - BACKGROUND: A severe deficiency of ADAMTS13 activity contributes to the
      pathogenesis of thrombotic thrombocytopenic purpura (TTP). Measuring the activity
      of ADAMTS13 is helpful for the diagnosis of TTP and the prognostic monitor in TTP
      patients. Most available assays are cumbersome and costly, so not easily adapted
      to routine laboratories. ADAMTS13 cleaves von Willebrand factor (VWF) within the
      domain A2, located between domains A1 and A3. Therefore, specific assays for
      ADAMTS13 activity could be based on the different structures of VWF before and
      after the cleavage. Using this hypothesis we try to establish a new and simple
      method to determine ADAMTS13 activity. METHODS: First, plasma samples were
      exposed in denaturing condition to allow cleavage of VWF by ADAMTS13. Then, the
      ADAMTS13 activity was measured with two novel monoclonal antibodies, SZ-129 and
      SZ-125, which specifically recognize the VWF A1 and A3 domains by using a two
      site sandwich ELISA. Compared with a residual-collagen binding assay (R-CBA),
      plasma ADAMTS13 activities in 161 samples were assessed, and the inhibitory
      activities of ADAMTS13 autoantibody in 24 TTP patients were determined. The
      relationship of these two assays was analyzed by linear correlation, and the
      sensitivity and specificity of the new assay was also evaluated. RESULTS: Plasma
      ADAMTS13 activities in normal people and TTP, acute myocardial infarction (AMI),
      and idiopathic thrombocytopenic purpura (ITP) patients determined by the new
      assay were (89.75 +/- 7.93)%, (17.63 +/- 18.71)%, (68.55 +/- 18.08)%, (85.83 +/-
      9.84)%, respectively. Results were consistent with those of R-CBA, the squared
      correlation factor was 0.9183 of the two assays. The new assay can easily
      discriminate a TTP plasma sample from a non-TTP plasma sample (P < 0.01), and the
      coefficient of variation for the new assay was 6.17%. In 23 idiopathic TTP
      patients, the inhibitor activity of ADAMTS13 autoantibody ranged from 12% to
      100%, while no inhibitory activity was detected in one hereditary TTP patient.
      CONCLUSION: This new and simple assay for ADAMTS13 activity could be used
      routinely in the clinic to determine the activity of ADAMTS13.

PMID- 20819569
TI  - Inhibition of tau hyperphosphorylation and beta amyloid production in rat brain
      by oral administration of atorvastatin.
AB  - BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder and the
      leading cause of dementia in the elderly. The two hallmark lesions in AD brain
      are deposition of amyloid plaques and neurofibrillary tangles (NFTs).
      Hypercholesteremia is one of the risk factors of AD. But its role in the
      pathogenesis of AD is largely unknown. The aim of this study was to investigate
      the relationship between hypercholesteremia and tau phosphorylation or beta
      amyloid (Abeta), and evaluate the effect of atorvastatin on the level of tau
      phosphorylation and Abeta in the brains of rats fed with high cholesterol diet.
      METHODS: Sprague-Dawley (SD) rats were randomly divided into normal diet control
      group, high cholesterol diet group, and high cholesterol diet plus atorvastatin
      (Lipitor, 15 mg x kg(-1) x d(-1)) treated group. Blood from caudal vein was
      collected to measure total cholesterol (TC), triglyceride (TG), low density
      lipoprotein (LDL) and high-density lipoprotein (HDL) at the end of the 3rd and
      the 6th months by an enzymatic method. The animals were sacrificed 6 months later
      and brains were removed. All left brain hemispheres were fixed for
      immunohistochemistry. Hippocampus and cerebral cortex were separated from right
      hemispheres and homogenized separately. Tau phosphorylation and Abeta in the
      brain tissue were determined by Western blotting (using antibodies PHF-1 and Tau
      1) and anti-Abeta40/anti-Abeta42, respectively. RESULTS: We found that high
      cholesterol diet led to hypercholesteremia of rats as well as
      hyperphosphorylation of tau and increased Abeta level in the brains. Treatment of
      the high cholesterol diet fed rats with atorvastatin prevented the changes of
      both tau phosphorylation and Abeta level induced by high cholesterol diet.
      CONCLUSIONS: Hypercholesteremia could induce tau hyperphosphorylation and Abeta
      production in rat brain. Atorvastatin could inhibit tau hyperphosphorylation and
      decrease Abeta generation. It may play a protective role in the patho-process of
      hypercholesteremia-induced neurodegeneration in the brain.

PMID- 20819570
TI  - Assessment of pancreatic carcinoma cell chemosensitivity using a three
      dimensional culture system.
AB  - BACKGROUND: Monolayer cell culture models are the traditional culture models used
      for in vitro research of pancreatic carcinoma chemosensitivity. However, these
      models neglect the interactions between tumor cells and the impact of the tumor
      microenvironment. Such tumor cell monolayers poorly mimic the solid tumor
      microenvironment. The present study aimed to investigate the chemosensitivity
      characteristics of pancreatic cancer cells in a three-dimensional culture system
      by analyzing the differences in drug sensitivity between a scattered cell culture
      model and a multicellular spheroid culture model. METHODS: Three pancreatic
      cancer cell lines (SW1990, ASPC-1 and PCT-3) were cultured in three-dimensional
      collagen gels as well as in traditional two-dimensional monolayers. The
      chemosensitivities of the pancreatic carcinoma cells to 5-fluorouracil (5-FU),
      gemcitabine, and oxaliplatin in vitro were detected by both the Cell Counting Kit
      8 test and the collagen gel droplet-embedded culture drug-sensitivity test.
      RESULTS: In the two-dimensional culture model, differences in the
      chemosensitivities of the cloned pancreatic carcinoma cells and scattered cells
      existed for some concentrations of 5-FU, gemcitabine and oxaliplatin. In the
      three-dimensional culture model, there were significant differences in the
      chemosensitivities of the pancreatic cancer cells between the scattered cells and
      multicellular spheroids (P < 0.05). CONCLUSION: Pancreatic carcinoma cells
      exhibit multicellular resistance in three-dimensional cultures.

PMID- 20819571
TI  - Neural endoscopic assisted micro-invasive management of Chiari I malformation.
AB  - BACKGROUND: In order to make posterior fossa decompression for the management of
      Chiari I malformation simple and less invasive while using direct visualization,
      a novel solely endoscopic procedure has been employed for the decompression of
      Chiari malformation type I. The objective of this study was to present neural
      endoscopic posterior fossa decompression and atlas laminectomy for Chiari type I
      patients. METHODS: Twenty-one patients with Chiari type I underwent neural
      endoscopic posterior fossa decompression and atlas laminectomy. We described the
      procedure for neural endoscopic posterior fossa decompression and atlas
      laminectomy. All patients in this series demonstrated cerebellar tonsil
      herniation below the foramen magnum in addition to syringomyelia. All patients in
      the reviewed study underwent preoperative MRI as well as 3-month postoperative
      MRI. Additional follow-up MRI varied but was usually repeated 12 months to 18
      months after surgery. Postoperative MRI studies were retrospectively reviewed and
      compared with preoperative studies. RESULTS: All patients showed clinical
      improvements, and none had any complications. Patients with syringomyelia had
      symptoms entirely disappear. Eleven patients (52.4%) experienced radiographic
      improvement in syringomyelia (decreased size or resolution) during the follow-up
      period. Nine patients (42.8%) demonstrated decreased syrinx size and four (19%)
      demonstrated resolved syrinx. Of the 15 patients with symptomatic syringomyelia,
      11 (73.3%) experienced symptomatic improvement. The median time to symptom
      improvement was four months after surgery. Post surgical MRI examinations
      indicated complete and sufficient decompression of foramen magnum region.
      CONCLUSIONS: Endoscope atlanto-occipital decompression surgery is an innovative,
      safe and effective surgical procedure. It has similar results compared to
      traditional surgery, however with the added advantages of being minimal invasive,
      having fewer complications, decreased influence on stability of occipital bony
      structure, and a faster recovery as well as reduced hospital stay and expenses.

PMID- 20819572
TI  - Off-line analysis of single-unit neuronal discharge in the globus pallidus region
      in Parkinson's disease.
AB  - BACKGROUND: The accuracy of microelectrode-guided localization can make the
      operation safe and effective, but only experienced neurosurgeons are capable of
      performing this operation. A good index to identify neuronal discharges between
      globus pallidus interna and globus pallidus externa is needed. The aim of this
      research was to establish a good and practical electrophysiologic index to
      distinguish neuronal discharge in the interior globus pallidus from neuronal
      discharge in the exterior globus pallidus region of the brain in Parkinson's
      disease. The effect of neurons having an atypical discharge on successful
      surgical localization was also quantitatively evaluated. METHODS: The study
      included 30 patients with primary Parkinson's disease who underwent pallidotomy
      between September 2000 and October 2002. During each pallidotomy, the neuronal
      discharges in the pallidum and its vicinity were recorded. The recorded spikes
      were used to calculate the frequency, burst index, pause index, and pause ratio
      of the single-unit discharge. The interior and exterior globus pallidus regions
      were compared in terms of frequency, burst index, pause index, and pause ratio.
      The sensitivity, specificity, false-negative ratio, false-positive ratio, and
      accuracy of those indices were then evaluated. RESULTS: The values of frequency,
      burst index, pause index, and pause ratio in the interior globus pallidus were
      (96 +/- 43) Hz, 2.31 +/- 1.81, 0.05 +/- 0.05, and 0.27 +/- 0.28, respectively,
      and in the exterior globus pallidus were (59 +/- 27) Hz, 0.88 +/- 0.63, 0.20 +/-
      0.14, and 1.54 +/- 1.17, respectively. Use of the four indices to distinguish the
      two neuron types produced a sensitivity of 0.84, 0.78, 0.77, and 0.93 with a
      specificity of 0.64, 0.79, 0.88, and 0.87, respectively. The false-positive ratio
      was 0.36, 0.21, 0.12, and 0.13 and the false-negative ratio was 0.16, 0.22, 0.23,
      and 0.07 while the accuracy was 0.72, 0.79, 0.80, and 0.90, respectively.
      CONCLUSIONS: Pause ratio is a relatively reliable index to distinguish neuronal
      discharges between the interior and exterior globus pallidus regions in
      Parkinson's disease. The effect of neurons with atypical discharge on the
      successful surgical localization would be reduced to 10% when the pause ratio is
      used as the index.

PMID- 20819573
TI  - Ammonia induces upregulation of aquaporin-4 in neocortical astrocytes of rats
      through the p38 mitogen-activated protein kinase pathway.
AB  - BACKGROUND: Astrocyte swelling is an important consequence of hepatic
      encephalopathy, and aquaporin-4 has been reported to play a vital role in this
      swelling. Ammonia causes astrocyte swelling and is also known to modulate
      aquaporin-4 expression in the astrocyte foot processes. The purpose of this study
      was to explore the mechanism of ammonia-induced aquaporin-4 expression, which has
      been suggested to involve the p38 mitogen-activated protein kinase pathway.
      METHODS: We exposed cultured astrocytes to ammonium chloride, an in vitro model
      of hepatic encephalopathy. The purity of cultured astrocytes was evaluated by
      fluorescent glial fibrillary acidic protein labeling; cell morphology was
      assessed by light microscopy; the expression of aquaporin-4, phospho-p38, and p38
      were detected by Western blotting analysis. Statistical analysis was performed by
      one-way factorial analysis of variance, and the relationship between variables
      was calculated by linear regression using SPSS version 13.0 program for Windows
      (SPSS, Chicago, IL, USA). RESULTS: The purity of cultured astrocytes was (96.6 +/
      1.4)%. Astrocytes swelled significantly when exposed to 5 mmol/L ammonium
      chloride for 24 hours as compared to non-exposed astrocytes. Co-treatment with 10
      micromol/L SB203580 (an inhibitor of p38) attenuated the degree of ammonium
      chloride induced astrocyte swelling. Western blotting analysis revealed that the
      expression levels of phospho-p38 and aquaporin-4 in ammonium chloride treated
      cells were significantly increased relative to the control group (P < 0.001);
      SB203580 co-treatment inhibited the increased expression of phospho-p38 and
      aquaporin-4 relative to the ammonium chloride treated group (P = 0.002 and P =
      0.015 respectively). The phosphorylation of p38 and upregulation of aquaporin-4
      were highly correlated (r = 0.909). There were no significant differences in
      total p38 expression among the groups (P = 0.341). CONCLUSIONS: Ammonium chloride
      induced upregulation of aquaporin-4 in astrocytes is regulated by the p38 mitogen
      activated protein kinase pathway. Inhibiting p38 activation prevented ammonium
      chloride induced aquaporin-4 protein upregulation.

PMID- 20819574
TI  - Comparison of the major malformation rate of children conceived from
      cryopreserved embryos and fresh embryos.
AB  - BACKGROUND: Cryopreserved embryo transfer has become indispensable in
      reproductive technology. More and more children are conceived from frozen-thawed
      embryo transfer (FET). The risk of birth defects associated with frozen-thawed
      embryo transfer has been evaluated and conflict results are obtained. The aim of
      this study was to compare the rate of major malformations in children conceived
      from cryopreserved embryos with that of children from fresh embryos. METHODS: A
      retrospective analysis was performed on children conceived from frozen-thawed
      embryos and fresh embryos between January 2005 and December 2008 at the
      Reproduction Center of the Third Hospital, Peking University. The major
      malformation rates were compared between two groups for all children, as well as
      singletons or twins, separately. The frequencies of different subtypes of
      malformations classified according to different organ system were also compared.
      RESULTS: Thirty-four of 3125 children from cryopreserved embryos had a major
      malformation. The malformation rate was 1.09%, which was comparable to that for
      children after fresh embryos transfer (1.53% (55/3604), OR: 0.71, 95%CI; 0.46
      1.09). The malformation rate was also similar when the analysis was limited to
      children from cryopreserved embryos resulted from in vitro fertilization (IVF)
      (1.39%) and fresh IVF (1.3%). However, children from cryopreserved embryos
      resulted from intracytoplasmic sperm injections (ICSI) had much lower
      malformation rate than from fresh ICSI (0.63% vs.1.83%, OR: 0.34, 95%CI: 0.16
      0.75). No difference was found in the incidence of major malformations in
      singletons from cryo ICSI (0.73%) and fresh ICSI (1.9%), or from cryo IVF (1.49%)
      and fresh IVF (1.67%). Similar malformation rate was found in multiples from cryo
      ICSI (0.52%) and fresh ICSI (1.76%), or cryo IVF (1.30%) and fresh IVF (0.90%).
      The distribution and risk of the subtype of malformations, such as
      cardiovascular, gastrointestinal, neural tube, urogenital, musculoskeletal and
      facial abnormalities was not different between the cryo group and fresh group.
      CONCLUSIONS: The major malformation rate is similar between fetuses/children
      conceived from cryopreserved embryos and those from fresh embryos. Large
      prospective and long-term follow-up studies are needed to get exact results
      concerning the birth defects of the children born after cryopreserved embryos.

PMID- 20819576
TI  - Increased regional homogeneity in internet addiction disorder: a resting state
      functional magnetic resonance imaging study.
AB  - BACKGROUND: Internet addition disorder (IAD) is currently becoming a serious
      mental health problem among Chinese adolescents. The pathogenesis of IAD,
      however, remains unclear. The purpose of this study applied regional homogeneity
      (ReHo) method to analyze encephalic functional characteristic of IAD college
      students under resting state. METHODS: Functional magnetic resonanc image (fMRI)
      was performed in 19 IAD college students and 19 controls under resting state.
      ReHo method was used to analyze the differences between the average ReHo in two
      groups. RESULTS: The following increased ReHo brain regions were found in IAD
      group compared with control group: cerebellum, brainstem, right cingulate gyrus,
      bilateral parahippocampus, right frontal lobe (rectal gyrus, inferior frontal
      gyrus and middle frontal gyrus), left superior frontal gyrus, left precuneus,
      right postcentral gyrus, right middle occipital gyrus, right inferior temporal
      gyrus, left superior temporal gyrus and middle temporal gyrus. The decreased ReHo
      brain regions were not found in the IAD group compared with the control group.
      CONCLUSIONS: There are abnormalities in regional homogeneity in IAD college
      students compared with the controls and enhancement of synchronization in most
      encephalic regions can be found. The results reflect the functional change of
      brain in IAD college students. The connections between the enhancement of
      synchronization among cerebellum, brainstem, limbic lobe, frontal lobe and apical
      lobe may be relative to reward pathways.

PMID- 20819575
TI  - Reproducibility of RTVue retinal nerve fiber layer thickness and optic nerve head
      measurements in normal and glaucoma eyes.
AB  - BACKGROUND: RTVue spectral-domain optical coherence tomography (OCT) is a new,
      ultra high-speed and high-resolution instrument, potentially to measure the
      presence of glaucoma or its progression accurately. The objective of this study
      was to evaluate its reproducibility of retinal nerve fiber layer (RNFL) thickness
      and optic nerve head (ONH) measurements in normal and glaucoma eyes. METHODS:
      This study was an observational clinical study. One eye was selected randomly
      from each of 89 normal individuals and 63 glaucoma patients in a range of
      severity. RNFL thickness and ONH were measured 3 times on the same day to
      determine intrasession variability. The same instrument was used by the same
      operator for all scans. Intrasession within-subject standard deviation (Sw),
      precision (1.96 x Sw), coefficient of variation (CVw, 100 x Sw/overall mean), and
      intraclass coefficient (ICC) were calculated to evaluate reproducibility.
      RESULTS: RTVue OCT demonstrated double hump patterns in the RNFL profiles. High
      reproducibility was observed in all ONH parameters. For normal eyes, the value of
      ICC ranged between 0.98 and 1.00. For eyes with different extent of glaucoma, it
      ranged between 0.94 and 1.00. High reproducibility was also observed in RNFL
      thickness measurements. The values of ICC for averaged RNFL thickness ranged
      between 0.95 and 1.00 in all cases. For regional parameters, it ranged from 0.94
      to 0.98 for normal eyes, 0.94 to 1.00 for mild glaucoma eyes, 0.87 to 1.00 for
      moderate glaucoma eyes, and 0.77 to 0.97 for severe glaucoma eyes. The nasal
      regions of severe glaucoma appeared to be most variable, as nasal lower region
      and inferior nasal region had the ICC values of 0.77 and 0.87. CONCLUSION:
      Reproducibility of RTVue RNFL and ONH measurements was excellent in normal and
      glaucoma groups.

PMID- 20819577
TI  - Comparison of a glucose consumption based method with the CLSI M38-A method for
      testing antifungal susceptibility of Trichophyton rubrum and Trichophyton
      mentagrophytes.
AB  - BACKGROUND: The prevalence of dermatophytoses and the development of new
      antifungal agents has focused interest on susceptibility tests of dermatophytes.
      The method used universally for susceptibility tests of dermatophytes was
      published as document (M38-A) in 2002 by the Clinical and Laboratory Standards
      Institute (CLSI), dealing with the standardization of susceptibility tests in
      filamentous fungi, though not including dermatophytes especially. However, it is
      not a very practical method for the clinical laboratory in routine susceptibility
      testing. In this test, we developed a novel rapid susceptibility assay-glucose
      consumption method (GCM) for dermatophytes. METHODS: In this study, we
      investigated the antifungal susceptibilities of dermatophytes to itraconazole
      (ITC), voriconazole (VOC), econazole nitrate (ECN) and terbinafine (TBF) by
      glucose consumption method (GCM), in comparison to the Clinical and Laboratory
      Standards Institute (CLSI) M38-A method. Twenty-eight dermatophyte isolates,
      including Trichophyton rubrum (T. rubrum) (n = 14) and Trichophyton
      mentagrophytes (T. mentagrophytes) (n = 14), were tested. In the GCM, the minimum
      inhibitory concentrations (MICs) were determined spectrophotometrically at 490 nm
      after addition of enzyme substrate color mix. For the CLSI method, the MICs were
      determined visually. RESULTS: Comparison revealed best agreement for TBF against
      T. mentagrophytes and T. rubrum, since MIC range, MIC50, and MIC90 were identical
      from two methods. However, for ITC and VOC, GCM showed wider MIC ranges and
      higher MICs than CLSI methods in most isolates. For ECN against T. rubrum, high
      MICs were tested by GCM (0.125-16 microg/ml) but not M38-A method (0.5-1
      microg/ml). The overall agreements for all isolates between the two methods
      within one dilution and two dilutions for ITC, VOC, ECN and TBF was 53.6% and
      75.0%, 57.1% and 75.0%, 82.1% and 89.3%, and 85.7 and 85.7%, respectively.
      CONCLUSION: Measurement of glucose uptake can predict the susceptibility of T.
      rubrum and T. mentagrophytes to ECN and TBF.

PMID- 20819578
TI  - Ursolic acid induces human hepatoma cell line SMMC-7721 apoptosis via p53
      dependent pathway.
AB  - BACKGROUND: Ursolic acid (UA) is a ubiquitous molecule in the plant kingdom with
      specific anticancer effects that have been shown in vitro and in vivo. Although
      UA can inhibit the proliferation of liver cancer cells and induce apoptosis of
      many types of tumor cells, the molecular mechanism of its anti-hepatoma activity
      is still not well defined. The objective of this study was to investigate the
      inhibitory effect and mechanisms of UA on the human hepatoma cell line SMMC-7721.
      METHODS: After treatment with UA, the growth inhibition of SMMC-7721 cells was
      assessed by MTT assay. Cells were also evaluated by flow cytometric analysis,
      Wright-Giemasa staining, Hoechst 33258 staining and transmission electron
      microscope after they were induced by UA. DNA microarray technology was used to
      investigate the gene expression pattern of SMMC-7721 cells exposed to UA 40
      micromol/L. The molecular mechanism of cells death was analyzed by real-time RT
      PCR and Western blotting. RESULTS: The proliferation of SMMC-7721 cells was
      significantly inhibited in a dose- and time-dependent manner after UA treatment.
      UA induced cell cycle arrest and apoptosis. The DNA microarray analysis indicated
      that 64 genes were found to be markedly up- or down-expressed, including GDF15,
      SOD2, ATF3, and fos. The result of Western blotting showed the apoptotic proteins
      p53 and Bax were up-regulated while the anti-apoptotic protein Bcl-2 was down
      regulated. Real-time RT-PCR confirmed UA could up-regulate the mRNA expressions
      of GDF15, SOD2, ATF3 and down-regulate the mRAN expression of fos. Meanwhile
      these effects were partly blocked by pretreatment with the p53 inhibitor Pft
      alpha. CONCLUSION: Activation of the p53 pathway is involved in UA inhibition of
      SMMC-7721 human hepatocellular carcinoma cell growth and induction of apoptosis.

PMID- 20819579
TI  - Effect of Helicobacter pylori eradication on iron deficiency.
AB  - BACKGROUND: Iron deficiency (ID) is still a great challenge to health care
      worldwide. Results of randomized controlled trials (RCTs) evaluating the effect
      of Helicobacter pylori (H. pylori) eradication on ID are contradictory. This
      study aimed to evaluate the effect of H. pylori eradication on ID with a meta
      analysis of RCTs. METHODS: Five electronic databases were searched for RCTs
      evaluating the effect of H. pylori eradication on ID. Summary effects were
      assessed with the methods recommended by the Cochrane Collaboration. RESULTS:
      Eight studies involving 800 participants were included in this meta-analysis. The
      overall analysis showed that H. pylori eradication accelerated the improvement of
      ferritin levels in ID people (mean difference (MD), 7.74 microg/L; 95%CI, 4.61 to
      10.88; P < 0.00001). In a subgroup analysis, H. pylori eradication accelerated
      the improvement of ferritin levels one month (MD, 7.00 microg/L; 95%CI, 1.72 to
      12.28; P = 0.009) and two months (MD, 9.80 microg/L; 95%CI, 2.22 to 17.40; P =
      0.01) after the initiation of treatment. However, H. pylori eradication did not
      show a beneficial effect on the improvement of ferritin levels three months (MD,
      7.20 microg/L; 95%CI, -3.25 to 17.65; P = 0.18), one year (MD, 10.17 microg/L;
      95%CI, -1.00 to 21.34; P = 0.07) and forty months (MD, 1.00 microg/L; 95%CI, 
      0.57 to 2.57; P = 0.21) after the initiation of treatment. H. pylori eradication
      did not accelerate the improvement of hemoglobin concentrations in the overall
      analysis (MD, 0.38 g/dl; 95%CI, -0.45 to 1.22; P = 0.37). In a subgroup analysis,
      H. pylori eradication did not accelerate the improvement of hemoglobin
      concentrations one month (MD, -0.48 g/dl; 95%CI, -2.39 to 1.42; P = 0.62), three
      months (MD, -0.10 g/dl; 95%CI, -0.35 to 0.15; P = 0.44) and forty months (MD,
      0.10 g/dl; 95%CI, -0.37 to 0.57; P = 0.68) after the initiation of treatment.
      However, H. pylori eradication accelerated the improvement of hemoglobin
      concentrations two months (MD, 1.96 g/dl; 95%CI, 1.48 to 2.44; P < 0.00001) and
      one year (MD, 0.37 g/dl; 95%CI, 0.08 to 0.65; P = 0.01) after the initiation of
      treatment. CONCLUSIONS: H. pylori eradication is likely to improve the absorption
      of oral ferrous. H. pylori infection may play some roles in the development of
      ID.

PMID- 20819580
TI  - Protective effect of glycine on liver injury during liver transplantation.

PMID- 20819581
TI  - Detection of biomarkers in children with Wilms' tumor using proteinchip
      technology.

PMID- 20819582
TI  - Hybrid treatment of recurring thoracoabdominal aortic aneurysm concomitant with
      retrograde type A aortic dissection.

PMID- 20819583
TI  - Sezary syndrome: a rare form of cutaneous T-cell lymphoma.

PMID- 20819584
TI  - Medical screening: to be or not to be?

PMID- 20819585
TI  - A case of Poncet's disease: retroperitoneal tuberculous lymphadenitis and
      polyarthritis.

PMID- 20819586
TI  - Should primary percutaneous coronary intervention be always the first option for
      patients with an ST elevation myocardial infarction?

PMID- 20819588
TI  - Comparative study of 4Fr catheters using the ACIST variable rate injector system
      versus 6Fr catheters using hand manifold in diagnostic coronary angiography via
      transradial approach.
AB  - BACKGROUND: The transradial approach is regarded as a useful vascular site for
      coronary procedures. The aim of this study was to test whether 4Fr catheters
      assisted by ACIST variable rate injector system can produce comparable
      angiographic quality and reduce the risk of radial artery injury compared to hand
      manifold 6 Fr catheters. METHODS: A total of 1816 patients were studied
      consecutively, among whom 856 patients received coronary angiography by 4 Fr
      catheters (4Fr group) and 960 patients by 6 Fr catheters (6Fr group).
      Angiographic and procedural characteristics were observed and recorded. The
      luminal inner radial arterial diameter before and after the procedure were
      collected. RESULTS: The baseline clinical characteristics were similar in both
      groups. There were no significant differences in procedure time, radiation dose
      and quality scores in both groups (P > 0.05), but more contrast media was
      delivered in the 6Fr group (P < 0.001). The mean radial arterial diameter six
      months after the procedure in the 6Fr group reduced significantly compared to
      that measured one day prior to the procedure (P < 0.001). CONCLUSIONS: Coronary
      angiography using the 4Fr catheters with Acist power injection system can achieve
      an acceptable diagnostic quality while at the same time minimizing radial artery
      injury and contrast media consumption.

PMID- 20819587
TI  - Thorombolytic therapy with rescue percutaneous coronary intervention versus
      primary percutaneous coronary intervention in patients with acute myocardial
      infarction: a multicenter randomized clinical trial.
AB  - BACKGROUND: Although thrombolytic therapy with rescue percutaneous coronary
      intervention (PCI) is a common treatment strategy for ST-segment elevation acute
      myocardial infarction (STEMI), scant data are available on its efficacy relative
      to primary PCI, and comparison was therefore the aim of this study. METHODS: This
      multicenter, open-label, randomized, parallel trial was conducted in 12 hospitals
      on patients (age < or = 70 years) with STEMI who presented within 12 hours of
      symptom onset (mean interval > 3 hours). Patients were randomized to three
      groups: primary PCI group (n = 101); recombinant staphylokinase (r-Sak) group (n
      = 104); and recombinant tissue-type plasminogen activator (rt-PA) group (n =
      106). For all patients allocated to the thrombolytic therapy arm, coronary
      angiography was performed at 90 minutes after drug therapy to confirm infarct
      related artery (IRA) patency; rescue PCI was performed in cases with TIMI flow
      grade < or = 2. Bare-metal stent implantation was planned for all patients.
      RESULTS: After randomization it required an average of 113.4 minutes to start
      thrombolytic therapy (door-to-needle time) and 141.2 minutes to perform first
      balloon inflation in the IRA (door to balloon time). Rates of IRA patency (TIMI
      flow grade 2 or 3) and TIMI flow grade 3 were significantly lower in the
      thrombolysis group at 90 minutes after drug therapy than in the primary PCI group
      at the end of the procedure (70.5% vs. 98.0%, P < 0.0001, and 53.0% vs. 85.9%, P
      < 0.0001, respectively). Rescue PCI with stenting was performed in 117 patients
      (55.7%) in the thrombolytic therapy arm. Rates of patency and TIMI flow grade 3
      were still significantly lower in the rescue PCI than in the primary PCI group
      (88.9% vs. 97.9%, P = 0.0222, and 68.4% vs. 85.0%, P = 0.0190, respectively). At
      30 days post-therapy, mortality rate was significantly higher in the thrombolysis
      combined with rescue PCI group than in primary PCI group (7.1% vs. 0, P =
      0.0034). Rates of death/MI and bleeding complications were significantly higher
      in the thrombolysis with rescue PCI group than in the primary PCI group (10.0%
      vs. 1.0%, P = 0.0380, and 28.10% vs. 8.91%, P = 0.0001, respectively).
      CONCLUSIONS: Thrombolytic therapy with rescue PCI was associated with
      significantly lower rates of coronary patency and TIMI flow grade 3, but with
      significantly higher rates of mortality, death/MI and hemorrhagic complications
      at 30 days, as compared with primary PCI in this group of Chinese STEMI patients
      with late presentation and delayed treatments.

PMID- 20819589
TI  - Gender difference of clinical characteristics in Chinese patients with
      spontaneous variant angina.
AB  - BACKGROUND: Spontaneous attack of variant angina (VA) is a unique component of
      coronary artery disease (CAD), and associated with severe cardiac events.
      However, no data are available regarding sex differences in Chinese patients with
      spontaneous attacks of VA. Accordingly, the present retrospective study was
      initiated to evaluate the Clinical characteristics of Chinese female patients
      with spontaneous attacks of VA. METHODS: From January 2003 to January 2008, a
      total of 209 patients were diagnosed to have had a spontaneous attack of VA at Fu
      Wai Hospital. Of them, 27 were female, and their clinical findings were collected
      and compared with male patients for aspects of risk factors, clinical features
      and angiographical findings. RESULTS: Spontaneous attacks of VA was relatively
      uncommon in female (12.9%) compared with male patients. The female patients were
      less likely to have a history of smoking (14.8% vs. 79.7%, P < 0.001), more
      likely to have a family history of CAD (33.3% vs. 11.0%, P < 0.01), and to have
      had a greater incidence of ventricular fibrillation during attack (11.1% vs.
      2.2%, P < 0.05). There were no significant differences in other characteristics
      between the two groups. CONCLUSION: Chinese female patients who experienced a
      spontaneous attack of VA had the characteristics of less smoking history, more
      family history of CAD and higher occurrence of ventricular fibrillation than male
      patients.

PMID- 20819590
TI  - Angiotensin-converting enzyme gene I/D genotype affected metoprolol-induced
      reduction in 24-hour average heart rate.
AB  - BACKGROUND: Genetic factors can influence antihypertensive response to
      metoprolol, and many studies focused on the relationship between the genotype in
      beta1-adrenergic receptor and blood pressure (BP), little was known about the
      association of angiotensin-converting enzyme (ACE) genotype with the therapeutic
      result of metoprolol. The present study aimed to investigate whether the ACE gene
      insertion (I)/deletion (D) polymorphism is related to the response to metoprolol
      in Chinese Han hypertensive patients. METHODS: Ninety-six patients with essential
      hypertension received metoprolol (100 mg once daily) as monotherapy for 8 weeks.
      Twenty-four hours ambulatory blood pressure monitoring and dynamic
      electrocardiogram were performed before and after treatment. Genotyping analysis
      was performed using PCR. The association of the ACE gene I/D polymorphism with
      variations in BP and heart rate (HR) was observed after the 8-week treatment.
      RESULTS: The patients with ACE gene II polymorphism showed greater reduction in
      24-hour average HR than those with ID or DD polymorphisms (P = 0.045), no effect
      of this genotype on the reduction in seating HR or in BP was observed. After
      adjusting for age, gender, body mass index, BP and HR at baseline, the ACE gene
      I/D polymorphism was still an independent predictor for variations in 24-hour
      average HR. CONCLUSIONS: The II polymorphism in ACE gene could be a candidate
      predictor for greater reduction in 24-hour average HR in Chinese Han hypertensive
      patients treated by metoprolol. Greater benefits would be obtained by patients
      with II polymorphism from the treatment with metoprolol. Larger studies are
      warranted to validate this finding.

PMID- 20819592
TI  - Predictive value of serum uric acid on cardiovascular disease and all-cause
      mortality in urban Chinese patients.
AB  - BACKGROUND: The association between increased serum uric acid (SUA) levels and
      cardiovascular risk has been debated for decades. Several large studies have
      provided conflicting results regarding the clinical significance of elevated SUA
      levels in cardiovascular disease (CVD) or cerebrovascular disease. The aim of
      this study was to investigate the relationship between SUA and CVD and all-cause
      mortality and their potential diagnostic value. METHODS: A total of 3570 in
      patients ranging in age from 56 to 95 years (mean (67.36 +/- 11.36) years) were
      selected from 20 hospitals in Beijing and Shanghai. A carefully designed
      questionnaire was used to gather baseline data of each patient. All patients were
      divided into two main groups according to their SUA levels: high SUA and normal
      SUA groups. Serum indices and other important parameters were measured. RESULTS:
      Compared with normal SUA group, high SUA group had significant difference in
      systolic blood pressure (SBP), total cholesterol (TC), triglyceride (TG), high
      density lipoprotein cholesterol (HDL-C), body mass index (BMI), and age (P < 0.05
      or P < 0.01). High SUA prevailed in female and patients with history of essential
      hypertension, while history of smoking and diabetes showed no significant
      difference between two groups. All-cause and CVD mortality occurred more
      frequently in high SUA group than in normal SUA group. In the accumulative
      survival analysis, high SUA group had lower survival rate than normal SUA group
      both in CVD and all-cause mortality. COX regression analysis indicated that the
      history of smoking, age and high SUA were independent risk factors for the
      development of CVD. CONCLUSIONS: These preliminary observations suggest that
      patients with high SUA levels would face higher risk of mortality. SUA
      measurement may be applied as a routine predictor for clinical assessment.

PMID- 20819593
TI  - Association between fifteen risk factors and progressing ischemic stroke in the
      Han population of northeast China.
AB  - BACKGROUND: The mortality and disability associated with progressing ischemic
      stroke are much higher than general ischemic stroke. This study was conducted to
      determine the risk factors for progressing ischemic stroke in the Han population
      of northeast China. METHODS: A total of 2511 patients with ischemic stroke within
      24 hours admitted to Department of Neurology, First Affiliated Hospital of Harbin
      Medical University were studied, from November 2007 to May 2009. All of the
      patients were classified into the progressing or non-progressing group according
      to the scores of the Scandinavian Neurological Stroke Scale. Fifteen putative
      risk factors were evaluated. The influence of risk factors for progressing
      ischemic stroke was analyzed with the simple Logistic analysis, the multiple
      Logistic analysis, and the stepwise Logistic regression model. All the
      statistical analysis was performed by SAS 9.1. RESULTS: Totally 359 (14.3%)
      patients met the criteria for progressing ischemic stroke. The Logistic analysis
      showed that age, family stroke history, smoking history, hypertension on
      admission, a drop in blood pressure after admission to the hospital, high serum
      glucose on admission, and fever were related to progressing ischemic stroke in
      the Han population of northeast China. CONCLUSION: People of the ischemic stroke
      with these factors are more likely to develop progressing ischemic stroke.

PMID- 20819594
TI  - Identification of compound heterozygous mutations in the ITGA2B gene in a Chinese
      patient with Glanzmann thrombasthenia.
AB  - BACKGROUND: Glanzmann thrombasthenia (GT) is an autosomal recessive bleeding
      disorder characterized by the tendency to hemorrhage and the inability of
      platelets to aggregate in response to agonists. GT is caused by a defect of the
      platelet glycoprotein IIb/IIIa complex. The objective of this study was to
      describe the clinical features and the genetic cause of GT in a 6-year-old girl
      from south China. METHODS: A three-generation family was studied. The proband
      patient aged 6 years and her parents undertook examinations of platelet counts,
      blood film, bleeding time, platelet aggregation, and flow cytometry. All coding
      exons of the ITGA2B and ITGB3 genes were amplified by polymerase chain reaction
      (PCR), and direct sequencing was performed for mutational screening on the
      patient and normal controls consisted of 52 healthy blood donors. Reverse
      transcription PCR was conducted to test for exon skipping. RESULTS: The proposita
      patient showed dispersing platelets, prolonged bleeding time, and severely
      reduced platelet aggregation in response to the physiological agonists adenosine
      diphosphate (ADP), epinephrine, collagen, and ristocetin. Flow cytometric
      measurements showed that the contents of alphaIIb and beta3 were significantly
      decreased. Sequencing results demonstrated two different types of heterozygous
      mutations existed in the alphaIIb gene (c.2930delG and IVS15-1delG). The compound
      mutations were also confirmed in the patient's mother and father separately.
      CONCLUSIONS: The alphaIIbbeta3 deficiency of the proband was caused by two
      compound ITGA2B mutations, which were first reported in Chinese GT patients. The
      IVS15-1delG was first confirmed to cause an exon skipping.

PMID- 20819595
TI  - Clinical features of multiple myeloma invasion of the central nervous system in
      Chinese patients.
AB  - BACKGROUND: Although neurologic manifestations often complicate the course of
      patients with multiple myeloma, direct central nervous system invasion is rare.
      This study explored the neurologic symptoms, signs, clinical features, therapy
      and prognosis of Chinese patients with central nervous system myeloma invasion.
      METHODS: The diagnosis, therapy and prognosis were analyzed retrospectively in 11
      Chinese multiple myeloma patients with central nervous system infiltration from a
      total of 625 patients who have been treated at Changzheng Hospital (Shanghai,
      China) between January 1993 and May 2009. Survival curve was constructed with the
      use of Kaplan-Meier estimates. RESULTS: There were 11 patients with central
      nervous system involvement from 625 multiple myeloma patients. The occurrence
      rate was 1.8%. Ten of the 11 patients had other extramedullary diseases. Symptoms
      included cerebral symptoms, cranial nerve palsies, and spinal cord or spinal
      nerve roots symptoms. Cerebrospinal fluid was abnormal in 7 patients, usually
      exhibiting pleocytosis and elevated protein content, plus positive cytologic
      findings. Specific magnetic resonance imaging findings suggestive of central
      nervous system invasion were found in 9 patients. After a median follow-up of 19
      months, 3 patients were alive. The median overall survival for all patients was
      23 months, while the median overall survival for patients after central nervous
      system invasion was merely 6 months. CONCLUSIONS: It is exceedingly rare for
      there to be central nervous system infiltration in multiple myeloma patients.
      When it occurs, the prognosis is extremely poor despite the use of aggressive
      local and systemic treatment including stem cell transplantation.

PMID- 20819598
TI  - Hepatic blood inflow occlusion with/without hemihepatic artery control versus the
      Pringle maneuver in resection of hepatocellular carcinoma: a retrospective
      comparative analysis.
AB  - BACKGROUND: The Pringle maneuver, which has been the standard for hepatic
      resection surgery for a long time, has the major flaw of ischemic damage in the
      liver. The aim of this research was to evaluate hepatic blood inflow occlusion
      with/without hemihepatic artery control vs. the Pringle maneuver in
      hepatocellular carcinoma (HCC) resection. METHODS: Two hundred and eighty-one
      cases of resection of HCC with hepatic blood inflow occlusion (with/without
      hemihepatic artery control) and the Pringle maneuver from January 2006 to
      December 2008 in our hospital were analyzed and compared retrospectively; among
      them 107 were in group I (Pringle maneuver), 98 in group II (hepatic blood inflow
      occlusion), and 76 in group III (hepatic blood inflow occlusion without
      hemihepatic artery control). The operation time, intraoperative blood loss,
      postoperative liver function and complications were used as the endpoints for
      evaluation. RESULTS: The operative duration and intraoperative blood loss of
      three groups showed no significant difference; alanine aminotransferase, total
      bilirubin and incidence of postoperative complications were significantly lower
      in groups II and III postoperation than those in group I. CONCLUSION: Hepatic
      blood inflow occlusion without hemihepatic artery control is safe, convenient and
      feasible for resection of HCC, especially for cases involving underlying diseases
      such as cirrhosis.

PMID- 20819599
TI  - Intraocular pressure lowering efficacy and safety of travoprost 0.004% as a
      replacement therapy in patients with open angle glaucoma or ocular hypertension.
AB  - BACKGROUND: Travoprost has been widely used for the treatment of patients with
      open-angle glaucoma (OAG) or ocular hypertension (OH). The aim of this study was
      to evaluate the intraocular pressure (IOP) lowering efficacy of travoprost 0.004%
      monotherapy in patients previously treated with other topical hypotensive
      medications, and in previously untreated patients. METHODS: This open-label, 12
      week study in 1651 adult patients with ocular hypertension or open-angle glaucoma
      who were untreated or required a change in therapy (due to either inadequate
      efficacy or safety issues) as judged by the investigator was conducted at 6 sites
      in China. Previously treated patients were instructed to discontinue their prior
      medications at the first visit. All the patients were dosed with travoprost
      0.004% once-daily at 8 p.m. in both eyes for 12 weeks. Efficacy and safety
      evaluations were conducted at week 4 and 12. IOP measurements were performed at
      the same time of day at the follow-up visits. RESULTS: For patients transitioned
      to travoprost, mean IOP reductions from baseline in untreated and treated
      patients with different prior medications at week 12 were: latanoprost, (4.3 +/-
      4.6) mmHg; beta-blocker, (6.3 +/- 4.0) mmHg; alpha-agonist, (7.5 +/- 4.3) mmHg;
      topical carbonic anhydrase inhibitors, (8.0 +/- 4.9) mmHg. All mean IOP changes
      from baseline were statistically significant (P < 0.001). No treatment-related
      serious adverse events were reported in this study. CONCLUSIONS: In patients
      treated with other hypotensive medications or untreated, the IOP reduction with
      travoprost was significant. The results of this study demonstrated the potential
      benefit of using travoprost as a replacement therapy in order to ensure adequate
      IOP control. Travoprost administered once daily was safe and well tolerated in
      patients with glaucoma or ocular hypertension.

PMID- 20819596
TI  - Circulating Dickkopf-1 and osteoprotegerin in patients with early and
      longstanding rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is characterized by inflammation of the
      synovial membrane, leading to invasion of synovial tissue into the adjacent
      cartilage matrix with degradation of articular cartilage and bone as a
      consequence. Dickkopf-1 (DKK-1) and osteoprotegerin (OPG) have been demonstrated
      to be key molecules involved in bone erosion and bone remodeling. The aim of this
      study was to explore the potential role of DKK-1 and OPG in different stage of
      RA. METHODS: The protein levels of DKK-1 and OPG were detected by ELISA. The
      serum samples were collected from 300 patients with RA and 60 healthy controls.
      Of which, 150 RA patients were defined as early RA (disease duration < or = 1
      year), and other 150 RA patients were defined as longlasting RA (disease duration
      > or = 5 years). At the time of serum sampling, various clinical and laboratory
      parameters were assessed. The correlations of DKK-1 or OPG and
      clinical/laboratory parameters were analyzed. RESULTS: The serum level of DKK-1
      was elevated in patients with longstanding RA compared with healthy controls,
      while no significant difference was observed between the two groups in the level
      of OPG. In contrast, in early RA patients, the circulating OPG was elevated,
      while there was no significant difference between the two groups in expression of
      DKK-1. The serum DKK-1 was correlated with Sharp score and DAS28 in longstanding
      RA patients. In early RA, age was the only parameter that was significantly
      related to serum OPG. CONCLUSIONS: There was a cross-talk between DKK-1 and OPG,
      which involved in bone destruction in RA. In different stage of RA, DKK-1 and OPG
      may play different roles in the pathogenesis of RA.

PMID- 20819600
TI  - Effect of lumbar angular motion on central canal diameter: positional MRI study
      in 491 cases.
AB  - BACKGROUND: Lumbar spinal stenosis is a common problem that is receiving
      attention with the advent of novel treatment procedures. Prior positional MRI
      studies demonstrated lumbar canal diameter changes with flexion and extension.
      There have not been any studies to examine the amount of spinal canal diameter
      change relative to the amount of angular motion. The purpose of this study was to
      evaluate the correlation between the lumbar canal diameter change and the angular
      motion quantitatively. METHODS: Positional MRI (pMRI) images for 491 patients,
      including 310 males and 181 females (16 years-85 years of age), were obtained
      with the subjects in sitting flexion 40 degree, upright, and with extension of 10
      degrees within a 0.6 T Positional MRI scanner. Quantitative measurements of the
      canal diameter and segmental angle of each level in the sagittal midline plane
      were obtained for each position. Then the diameter change and angular motion were
      examined for correlation during flexion and extension with linear regression
      analysis. RESULTS: The lumbar segmental angles were lordotic in all positions
      except L1-2 in flexion. The changes of canal diameters were statistically
      correlated with the segmental angular motions during flexion and extension (P <
      0.001). The amount of canal diameter change correlated with the amount of angular
      change and was expressed as a ratio. CONCLUSIONS: Positional MRI demonstrated the
      amount of spinal canal diameter change that was statistically correlated with the
      segmental angular motion of the spine during flexion and extension. These results
      may be used to predict the extent of canal diameter change when interspinous
      devices or positional changes are used to treat spinal stenosis and the amount of
      increased canal space may be predicted with the amount of angular or positional
      change of the spine. This may correlate with symptomatic relief and allow for
      improved success in the treatment of spinal stenosis.

PMID- 20819601
TI  - Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: a retrospective
      study of 78 pediatric cases in mainland of China.
AB  - BACKGROUND: The clinical characteristics of Epstein-Barr virus-associated
      hemophagocytic lymphohistiocytosis (EBV-HLH) are largely unreported in the
      pediatric patients in mainland of China. The main aim of this study was to
      recognize the clinical features of EBV-HLH in children and to explore its
      prognosis and risk factors. METHODS: A retrospective study was performed on 78
      pediatric patients with EBV-HLH who were admitted to Beijing Children's Hospital
      between 2003 and 2008. All patients' medical records were reviewed and analyzed.
      For each patient, demographic, clinical, laboratory and outcome information was
      collected. Statistical analysis was conducted via multivariate and univariate
      analysis. RESULTS: The age of onset peaked between 1 - 2 years and boys were more
      likely developed EBV-HLH. EBV-HLH occurred mainly in the serological pattern with
      EBV nuclear antigen (EBNA) positive (70.5%). The overall fatality of the disease
      was 56.7%. Twelve of the 39 fatalities (30.8%) died rapidly within 2 months after
      diagnosis. Multivariate analysis revealed that not receiving chemotherapy (P =
      0.002), > or = 4 weeks of illness prior to diagnosis (P = 0.004), and albumin
      levels < 20 g/L (P = 0.045) significantly predicted an increased fatality risk.
      CONCLUSIONS: EBV-HLH is a severe disease with a high fatality rate that occurs
      mainly in the serological pattern with EBNA positive. Early initiation of
      chemotherapy and timely diagnosis significantly improves survival rate. Practical
      strategies should focus on reducing the likelihood of early death.

PMID- 20819602
TI  - Study of the wavefront aberrations in children with amblyopia.
AB  - BACKGROUND: Amblyopia is a common ophthalmological condition and the wavefront
      aberrometer is a relatively new diagnostic tool used globally to measure optical
      characteristics of human eyes as well as to study refractive errors in amblyopic
      eyes. We studied the wavefront aberration of the amblyopic children's eyes and
      analyzed the mechanism of the wavefront aberration in the formation of the
      amblyopia, try to investigate the new evidence of the treatment of the amblyopia,
      especially in the refractory amblyopia. METHODS: The WaveScan Wavefront System
      (VISX, USA) aberrometer was used to investigate four groups of children under
      dark accommodation and cilliary muscle paralysis. There were 45 cases in the
      metropic group, 87 in the amblyopic group, 92 in the corrected-amblyopic group
      and 38 in the refractory amblyopic group. One-way analysis of variance (ANOVA), t
      test and multivariate linear regression were used to analyze all the data.
      RESULTS: Third order to 6th order aberrations showed a decreasing trend whereas
      in the higher order aberrations the main ones were 3rd order coma (Z(3)(-1)
      Z(3)(1)), trefoil (Z(3)(-3)-Z(3)(3)) and 4th order aberration (Z(4)(0)); and 3rd
      order coma represented the highest percentage of all three main aberrations.
      Within 3rd order coma, vertical coma (Z(3)(-1)) accounted for a greater
      percentage than horizontal coma (Z(3)(1)). Significant differences of vertical
      coma were found among all clinical groups of children: vertical coma in the
      amblyopic group (0.17 +/- 0.15) was significantly higher than in the metropic
      group (0.11 +/- 0.13, P < 0.05). In addition, the vertical coma in the refractory
      amblyopic group (0.19 +/- 0.15) was higher compared with the metropic group (P <
      0.05), the 5th order aberration (0.11 +/- 0.08) was also significantly higher
      than in the metropic group (0.07 +/- 0.04, P < 0.05). No significant difference
      was found in vertical coma and 5th order aberration between the corrected
      amblyopic group (0.13 +/- 0.11) and metropic group (0.07 +/- 0.04) (P > 0.05).
      CONCLUSIONS: Although lower order aberrations such as defocus (myopia and
      hyperopia) and astigmatism are major factors determining the quality of the
      retinal image, higher order aberrations also need to be considered in amblyopic
      eyes as their effects are significant.

PMID- 20819603
TI  - Study of an integrated non-motor symptoms questionnaire for Parkinson's disease.
AB  - BACKGROUND: Although the validity of non-motor symptoms screening questionnaire
      (NMSQuest) for Parkinson's disease has been verified in several recent
      researches, the specificity of the questionnaire is still in doubt. This study
      aimed to compare the non-motor symptoms (NMS) in Parkinson's disease (PD) with a
      medically ill control group. METHODS: In this study, the first comprehensive
      clinic-based NMS screening questionnaire for PD developed by the Parkinson's
      Disease Non-Motor Group (PDNMG) was used. Data from 90 PD patients and 270 sex
      and age-matched control subjects, including stroke (n = 90), heart disease (n =
      90) and diabetes (n = 90) were analyzed. RESULTS: Compared with control group,
      NMS was more common in PD; on an average, most PD patients reported more than 12
      non-motor items. There was a correlation of total NMS score in PD patients with
      Hoehn & Yahr Staging, but not with age, sex distribution, disease duration, or
      age at disease onset. Additionally, depression, constipation and impaired
      olfaction which occurred prior to the motor symptoms of PD were reported in this
      study. CONCLUSIONS: NMS are more common in PD patients. There are some NMS that
      occurred at the preclinical stage of PD and might predict the onset of motor
      symptoms of PD patients.

PMID- 20819604
TI  - Extracellular ascorbic acid fluctuation during the protective process of ischemic
      preconditioning in rabbit renal ischemia-reperfusion model measured.
AB  - BACKGROUND: Ascorbic acid has important antioxidant properties, and may play a
      role in the protective effects of ischemic preconditioning on later ischemia
      reperfusion. Herein, we examined the role of endogenous extracellular ascorbic
      acid in ischemic preconditioning in the kidney. METHODS: We developed a solitary
      rabbit kidney model where animals received ischemia-reperfusion only (ischemia
      reperfusion group, n = 15) or ischemic preconditioning followed by ischemia
      reperfusion (ischemic preconditioning group, n = 15). Ischemia-reperfusion was
      induced by occluding and loosening of the renal pedicle. The process of ischemic
      preconditioning included 15-minute brief ischemia and 10-minute reperfusion. In
      vivo microdialysis coupled with online electrochemical detection was used to
      determine levels of endogenous extracellular ascorbic acid in both groups. The
      extent of tissue damage was determined in kidney sections stained with
      hematoxylin and eosin. Serum creatinine and urea nitrogen were also detected to
      assess renal function. RESULTS: During ischemia-reperfusion, the extracellular
      ascorbic acid concentration during ischemia increased rapidly to the peak level
      ((130.01 +/- 9.98)%), and then decreased slowly to near basal levels. Similar
      changes were observed during reperfusion (peak level, (126.78 +/- 18.24)%). In
      the ischemic preconditioning group there was a similar pattern of extracellular
      ascorbic acid concentration during ischemic preconditioning. However, the
      ascorbic acid level was significantly lower during the ischemia and early
      reperfusion stage compared to the ischemia-reperfusion group. Additionally, the
      extent of glomerular ischemic collapse, tubular dilation, tubular denudation, and
      loss of brush border were markedly attenuated in the ischemic preconditioning
      group. Levels of serum creatinine and urea nitrogen were also decreased
      significantly in the ischemic preconditioning group. CONCLUSIONS: Ischemic
      preconditioning may protect renal tissue against ischemia-reperfusion injury via
      use of extracellular ascorbic acid. In vivo microdialysis coupled with online
      electrochemical detection is effective for continuous monitoring extracellular
      ascorbic acid in the renal cortex.

PMID- 20819605
TI  - Role of PI3K/Akt signaling in the protective effect of magnesium sulfate against
      ischemia-perfusion injury of small intestine in rats.
AB  - BACKGROUND: The protective effects of magnesium sulfate against ischemia
      reperfusion injury of the small intestine in Sprague-Dawley (SD) rats have been
      confirmed in our previous research. However, its exact mechanism is unclear. This
      study was to evaluate the role of PI3K/Akt signal pathway in the protective
      effect of magnesium sulfate against ischemia-reperfusion injury of the small
      intestine in SD rats. METHODS: Rat model of intestinal ischemia-reperfusion
      injury was used. The SD rats were divided into four groups randomly: sham
      operation group, ischemia-reperfusion group, magnesium sulfate group and
      magnesium sulfate plus LY294002 (an inhibitor of PI3K) group. The pathological
      changes of intestinal mucosa were examined; the activity of diamine oxidase (DAO)
      in plasma, the plasma contents of malondialdehyde (MDA), and apoptosis rate of
      the intestinal mucosal cells were determined and compared. The expression of p
      Akt was detected by Western blotting. RESULTS: There were more evident
      pathological changes of the intestinal mucosa (higher Chiu's score, P < 0.05),
      enhanced DAO activity (P < 0.05), elevated contents of MDA (P < 0.05), higher
      apoptosis rate (P < 0.05), and lower level of p-Akt (P < 0.05) in the ischemia
      reperfusion group compared with the sham operation group. There were less evident
      pathological changes of the intestinal mucosa (lower Chiu's score, P < 0.05),
      lower DAO activity (P < 0.05), lower contents of MDA (P < 0.05), and lower
      apoptosis rate (P < 0.05), but higher level of p-Akt (P < 0.05) in the magnesium
      sulfate group compared with the ischemia-reperfusion group. There were more
      evident pathological changes of the intestinal mucosa (higher Chiu's score, P <
      0.05), higher contents of MDA (P < 0.05), higher DAO activity (P < 0.05) and
      higher apoptosis rate (P < 0.05), and lower level of p-Akt (P < 0.05) in the
      magnesium sulfate plus LY294002 group compared with the magnesium sulfate group.
      CONCLUSIONS: Activation of PI3K/Akt signal pathway results in the reduction of
      cell apoptosis, which likely accounts for the protective effect of magnesium
      sulfate against intestinal ischemia-reperfusion injury.

PMID- 20819606
TI  - Effect of hypertonic saline resuscitation on heme oxygenase-1 mRNA expression and
      apoptosis of the intestinal mucosa in a rat model of hemorrhagic shock.
AB  - BACKGROUND: Massive blood loss due to trauma is the leading cause of death in
      trauma patients and military combatants. The fluid category of resuscitation for
      hypotensive trauma patients is open to debate. This study was conducted to
      investigate the early effects of hypertonic and isotonic saline solutions on heme
      oxygenase-1 (HO-1) mRNA expression and apoptosis in the intestinal mucosa of rats
      with hemorrhagic shock. METHODS: A model of severe hemorrhagic shock was
      established in 21 Sprague-Dawley rats. The rats were randomly divided into sham,
      normal saline resuscitation (NS), and hypertonic saline resuscitation (HTS)
      groups, with 7 in each group. We assessed and compared the HO-1 mRNA expression
      and apoptosis in the small intestinal mucosa of rats after hemorrhagic shock and
      resuscitation using the SYBR Green I fluorescence quantitative reverse
      transcriptase polymerase chain reaction, fluorescein-iso-thiocyanate-annexin
      V/propidium iodide double staining, and flow cytometry. RESULTS: In the early
      stage of hemorrhagic shock and resuscitation, marked apoptosis occurred in the
      small intestinal mucosa from both the NS and HTS groups. The apoptotic rate in
      the NS group was higher than that in the HTS group (P < 0.01). Among the three
      groups, HO-1 mRNA mucosa from the HTS group had the highest level of expression;
      however, the differences were not significant. There was a significant negative
      correlation between HO-1 mRNA expression and apoptosis in the small intestinal
      mucosa from the NS and HTS groups after hemorrhagic shock and resuscitation.
      CONCLUSIONS: In this rat model of severe hemorrhagic shock, HTS resuscitation
      with a small volume is more effective than NS resuscitation in reducing apoptosis
      of the intestinal mucosa. Further, HO-1 mRNA over-expression in the intestinal
      mucosa may be one of the molecular mechanisms of HTS in the resuscitation of
      hemorrhagic shock.

PMID- 20819607
TI  - Clinical frontiers in electrocardiographic early repolarization syndrome: does a
      good guy turn bad now?

PMID- 20819608
TI  - HIV microbicides: innovation and challenge.

PMID- 20819609
TI  - A novel mitofusin 2 gene mutation causing Charcot-Marie-Tooth type 2A disease in
      a Chinese family.

PMID- 20819610
TI  - Value of embolization of brain arteriovenous malformations with ethylene vinyl
      alcohol copolymer.

PMID- 20819611
TI  - Successful treatment of acute hemorrhagic cardiac temponade in a patient with
      hepatocellular carcinoma during percutaneous radiofrequency ablation.

PMID- 20819612
TI  - S578N mutation of the androgen receptor in an adolescent with complete androgen
      insensitivity syndrome.

PMID- 20819613
TI  - First successful bilateral living-donor lobar lung transplantation in China.

PMID- 20819614
TI  - Loeffler endocarditis: magnetic resonance imaging features of pre- and post
      operation.

PMID- 20819615
TI  - Bilateral primary breast lymphoma.

PMID- 20819616
TI  - Subarachnoid disseminative hemangiopericytoma of the spinal cord.

PMID- 20819617
TI  - Toward more uniform conflict disclosures: the updated ICMJE Conflict of Interest
      Reporting Form.

PMID- 20819618
TI  - Transcription factor HAND2 mutations in sporadic Chinese patients with congenital
      heart disease.
AB  - BACKGROUND: The basic helix-loop-helix transcription factor HAND2 plays an
      essential role in cardiac morphogenesis. However, the prevalence of HAND2
      mutations in congenial heart disease (CHD) and the correlation between the HAND2
      genotype and CHD phenotype have not been studied extensively. METHODS: We
      amplified the exons and the flanking intron sequences of the HAND2 gene in 131
      patients diagnosed with congenital defects of the right ventricle, outflow tract,
      aortic artery or cardiac cushion and confirmed the mutations by sequencing.
      RESULTS: Seven mutations including three missense mutations (P11R, S36N and
      V83L), one isonymous mutation (H14H) and three mutations in untranslated region
      (241A > G, 604C > T and 3237T > A) were identified in 12 out of the 131 patients.
      Both nonisonymous mutations are located in the transcriptional activation domain
      on the N-terminus. Only one mutation (S36N) was identified in 250 normal healthy
      controls. The distribution of 3637T > A is the unique one which was different
      between the 2 groups. CONCLUSIONS: HAND2 may be a potential candidate gene of
      stenosis of the right ventricle, outflow tract. Further study of those with a
      family history of HAND2 mutations will help convincingly relate their genotype to
      the pathogenesis of CHD.

PMID- 20819619
TI  - Prognostic value of baseline C-reactive protein levels in patients undergoing
      coronary revascularization.
AB  - BACKGROUND: C-reactive protein (CRP) is a lowly expressed marker for inflammatory
      response. This study aimed to evaluate the prognostic value of baseline CRP
      levels in patients undergoing coronary revascularization in the context of modern
      medical treatment. METHODS: This was a retrospective study in a single center.
      Four hundred and fourteen patients were enrolled, who underwent coronary
      revascularization and received adequate medication for secondary prevention of
      coronary heart disease. The study compared the follow-up clinical outcomes
      between high level CRP group (CRP > 5 mg/L) and low level one. The median follow
      up time was 551 days. RESULTS: Compared with low CRP group, the relative risk
      (RR) of the major adverse cardiovascular and cerebral events (MACCE) in high CRP
      group was 5.131 (95%CI: 1.864-14.123, P = 0.002). There were no significant
      differences in death, myocardial infarction and stroke during the follow-up
      between two groups, but a higher risk of re-revascularization was found in high
      CRP group (RR 6.008, 95%CI: 1.667-21.665, P = 0.006). Cox regression analysis
      showed that only CRP level could contribute to MACCE during the follow-up. MACCE
      free rate was much lower in high CRP group (Kaplan-Meier log-rank P < 0.001).
      CONCLUSION: In the context of modern medical treatment, the baseline level of CRP
      is an independent predictor for long-term prognosis in patients with coronary
      revascularization.

PMID- 20819621
TI  - Rapid hemodilution is associated with increased sepsis and mortality among
      patients with severe acute pancreatitis.
AB  - BACKGROUND: Hemoconcentration may be an important factor that determines the
      progression of severe acute pancreatitis (SAP). In addition, it has been proposed
      that biomarkers may be useful in predicting subsequent necrosis in SAP. However,
      it is still uncertain whether hemodilution in a short term can improve outcome.
      We aimed to investigate the effect of rapid hemodilution on the outcome of
      patients with SAP. METHODS: One hundred and fifteen patients were admitted
      prospectively according to the criteria within 24 hours of SAP onset. Patients
      were randomly assigned to either rapid hemodilution (hematocrit (HCT) < 35%, n =
      56) or slow hemodilution (HCT > or = 35%, n = 59) within 48 hours of onset.
      Balthazar CT scores were calculated on admission, day 7, and day 14, after onset
      of the disease. Time interval for sepsis presented, incidence of sepsis within 28
      days and in-hospital survival rate were determined. RESULTS: The amount of fluid
      used in rapid hemodilution was significantly more than that used in slow
      hemodilution (P < 0.05) on the admission day, the first day, and the second day.
      There were significant differences between the rapid and slow hemodilution group
      in terms of hematocrit, oxygenation index, pH values, APACHE II scores and organ
      dysfunction at different time during the first week. There were significant
      differences in the time interval to sepsis in rapid hemodilution ((7.4 +/- 1.9)
      days) compared with the slow hemodilution group ((10.2 +/- 2.3) days), and the
      incidence of sepsis (78.6%) was higher in the rapid group compared to the slow
      (57.6%) in the first 28 days. The survival rate of the slow hemodilution group
      (84.7%) was better than the rapid hemodilution (66.1%. P < 0.05). CONCLUSIONS:
      Rapid hemodilution can increase the incidence of sepsis within 28 days and in
      hospital mortality. Hematocrit should be maintained between 30%-40% in the acute
      response stage.

PMID- 20819620
TI  - Death mode-dependent reduction in succinate dehydrogenase activity in hair cells
      of aging rat cochleae.
AB  - BACKGROUND: Our previous studies have shown that both apoptosis and necrosis are
      involved in hair cell (HC) pathogenesis in aging cochleae. To better understand
      the biological mechanisms responsible for the regulation of HC death, we examined
      the activity of succinate dehydrogenase (SDH), a mitochondrial bioenergetic
      enzyme, in the HCs of aging cochleae. METHODS: The auditory brainstem response
      thresholds elicited by tone bursts at 4, 10 and 20 kHz were measured in both
      young (2-3 months) and aging (22-23 months) Wistar rats. SDH activity was
      evaluated with a colorimetric assay using nitroblue tetrazolium monosodium salt.
      The SDH-labeled organs of Corti were double stained with propidium iodide, a DNA
      intercalating fluorescent probe for illustration of HC nuclei. All the specimens
      were examined with fluorescence microscopy and confocal microscopy. RESULTS:
      Aging rats exhibited a significant elevation of ABR thresholds with threshold
      shifts being 34 dB at 20 kHz, 28 dB at 10 kHz, and 25 dB at 4 kHz. Consistent
      with the reduction in the cochlear function, aging cochleae exhibited the
      reduction of SDH staining intensity in the apical and the basal ends of the
      cochleae, where a large number of apoptotic, necrotic, and missing HCs were
      evident. The reduction in SDH staining appeared in a cell-death-mode dependent
      fashion. Specifically, SDH labeling remained in apoptotic HCs. In contrast, SDH
      staining was markedly reduced or absent in necrotic HCs. CONCLUSIONS: In the
      aging cochlea, SDH activity is preserved in HCs undergoing apoptosis, but is
      substantially reduced in necrosis. These results suggest that mitochondrial
      energetic function is involved in the regulation of cell death pathways in the
      pathogenesis of aging cochleae.

PMID- 20819622
TI  - Echocardiographic mapping of left ventricular resynchronization during cardiac
      resynchronization therapy procedures.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is an effective electrical
      therapy for patients with moderate to severe heart failure and cardiac
      dyssynchrony. This study aimed to investigate the degree of acute left
      ventricular (LV) resynchronization with biventricular pacing (BVP) at different
      LV sites and to examine the feasibility of performing transthoracic
      echocardiography (TTE) to quantify acute LV resynchronization during CRT
      procedure. METHODS: Fourteen patients with NYHA Class III-IV heart failure, LV
      ejection fraction < or = 35%, QRS duration > or = 120 ms and septal-lateral delay
      (SLD) > or = 60 ms on tissue Doppler imaging (TDI), underwent CRT implant. TDI
      was obtained from three apical views during BVP at each accessible LV site and
      SLD during BVP was derived. Synchronicity gain index (Sg) by SLD was defined as
      (1 + (SLD at baseline--SLD at BVP)/SLD at baseline). RESULTS: Seventy-two sites
      were studied. Positive resynchronization (R+, Sg > 1) was found in 42 (58%)
      sites. R+ was more likely in posterior or lateral than anterior LV sites (66% vs.
      36%, P < 0.001). Concordance of empirical LV lead implantation sites and sites
      with R+ was 50% (7/14). CONCLUSIONS: The degree of acute LV resynchronization by
      BVP depends on LV lead location and empirical implantation of LV lead results in
      only 50% concordance with R+. Performing TTE during CRT implantation is feasible
      to identify LV sites with positive resynchronization.

PMID- 20819623
TI  - Salmeterol/fluticasone treatment reduces circulating C-reactive protein level in
      patients with stable chronic obstructive pulmonary disease.
AB  - BACKGROUND: Evidence suggests that systemic inflammation may play an important
      role in the progression and morbidity of chronic obstructive pulmonary disease.
      It remains controversial whether inhaled corticosteroid in combination with a
      long-acting beta(2)-adrenoceptor agonist can attenuate systemic inflammation. We
      evaluated the effect of salmeterol/fluticasone propionate on circulating C
      reactive protein level in stable chronic obstructive pulmonary disease patients.
      METHODS: An open-label clinical trial was conducted to recruit 122 outpatients
      with stable moderate-to-severe chronic obstructive pulmonary disease from
      department of respiratory medicine in two teaching hospitals between June 2007
      and March 2008. Patients were randomized into two groups (1:1) to receive either
      the combination of 50 microg salmeterol and 500 microg fluticasone twice daily (n
      = 61), or the combination of 206 microg albuterol and 36 microg ipratropium q.i.d
      (n = 61) over 6 months. Circulating C-reactive protein concentrations were
      measured before randomization and during the follow-up. The efficacy of treatment
      was also assessed by spirometry, as well as health status and dyspnea score at
      baseline and after 6-month treatment. RESULTS: Baseline characteristics of two
      groups were similar. Compared with ipratropium/albuterol, the combination of
      salmeterol/fluticasone significantly reduced circulating level of C-reactive
      protein (-1.73 vs. 0.08 mg/L, respectively, P < 0.05) after 6-month treatment.
      Forced expiratory volume in one second (FEV(1)) and health status also improved
      significantly in salmeterol/fluticasone group compared with
      ipratropium/albuterol. Salmeterol/fluticasone treatment subjects who had a
      decrease of circulating C-reactive protein level had a significant improvement in
      FEV(1) and St George's Respiratory Questionnaire total scores compared with those
      who did not (185 vs. 83 ml and -5.71 vs. -1.79 units, respectively, both P <
      0.01). CONCLUSION: Salmeterol/fluticasone treatment reduced circulating C
      reactive protein concentration in clinically stable moderate-to-severe chronic
      obstructive pulmonary disease patients after 6-month treatment.

PMID- 20819624
TI  - Role of adrenalectomy in recurrent Cushing's disease.
AB  - BACKGROUND: Cushing's disease is a pituitary-dependent type of Cushing's
      syndrome. Treatment consists of pituitary surgery or radiotherapy, but the
      recurrence rate at 10 years is as high as 40%. Adrenalectomy is considered an
      effective treatment to refractory Cushing's disease. The objective of this study
      was to examine the efficacy of laparoscopic adrenalectomy and open adrenalectomy
      in Cushing's disease, focusing on reversing the sequelae of hypercortisolism and
      improving patients' quality of life. METHODS: Forty-three patients (29 women, 14
      men) with recurrent Cushing's disease after transsphenoidal operation underwent
      laparoscopic (n = 32) or open (n = 11) adrenalectomy from 2000 to 2008. Surgical
      results were evaluated for all the 43 patients. Patients completed a follow-up
      survey, including the short-form 36-item (SF-36) health survey. RESULTS: All the
      43 patients achieved clinical reversal of hypercortisolism after adrenalectomy.
      Time to symptom resolution varied from a few weeks to up to 3 years. Most
      physical changes had resolved by a mean of 8 months after surgery. These
      conditions were not significantly different between the laparoscopy and open
      groups. Median length of hospital stay was shorter in the laparoscopy group (4
      vs. 9 days; P < 0.001). Median follow-up was 48.5 months. Of the 34 (79%)
      patients available for follow-up, 22 (65%) had adrenocorticotropic hormone levels
      > 200 ng/ml and 6 (27%) had clinical Nelson syndrome. Four patients died by 75
      months after surgery. Using SF-36, 30 (88%) patients reported they felt their
      health status was good to excellent compared with 1 year before adrenalectomy;
      however, they showed significantly lower scores in all the 8 SF-36 parameters
      compared with the general population. No significant difference emerged in SF-36
      scores between the laparoscopy and open groups. CONCLUSIONS: Adrenalectomy showed
      high survival and clinical benefits in recurrent Cushing's disease patients.
      Despite patient-reported improvement in health after adrenalectomy, patients
      continue to experience poor health status compared with the general population.

PMID- 20819625
TI  - Diagnosis and fine localization of deletion region in Wolf-Hirschhorn syndrome
      patients.
AB  - BACKGROUND: Wolf-Hirschhorn syndrome (WHS) results from the partial deletion of
      4p. This study aimed to identify and fine map the chromosome deletion regions of
      Chinese children with Wolf-Hirschhorn syndrome among the developmental
      delay/mental retardation (DD/MR) patients. METHODS: We analyzed the relationship
      of phenotype and genotype. Inclusion criteria were: moderate to severe DD/MR, no
      definite perinatal brain injury, and no trauma, toxication, hypoxia, infection of
      central nervous system; routine karyotyping was normal, no evidence of typical
      inherited metabolic disorder or specific neurodegenerative disorders from cranial
      neuro-imaging and blood/urinary metabolic diseases screening; no mutation of FMR1
      in male patients, no typical clinical manifestation of Rett syndrome in female
      patients. Multiplex ligation-dependent probe amplification (MLPA) and Affymetrix
      genome-wide human SNP array 6.0 assays were applied to accurately define the
      exact size of subtelomeric aberration region of four WHS patients. RESULTS: All
      four WHS patients presented with severe DD, hypotonia and microcephaly, failure
      to thrive, 3/4 patients with typical facial features and seizures, 2/4 patients
      with congenital heart defects and cleft lip/palate, 1/4 patients with other
      malformations. The length of the deletions ranged from 3.3 Mb to 9.8 Mb. Two of
      four patients had "classic" WHS, 1/4 patients had "mild"-to-"classic" WHS, and
      1/4 patients had "mild" WHS. CONCLUSIONS: WHS patients in China appear to be
      consistent with those previously reported. The prevalence of signs and symptoms,
      distribution of cases between "mild" and "classic" WHS, and the correlation
      between length of deletion and severity of disease of these patients were all
      similar to those of the patients from other populations.

PMID- 20819626
TI  - Characteristics associated with falls among the elderly within aged care wards in
      a tertiary hospital: a retrospective.
AB  - BACKGROUND: Falls are the most frequently reported adverse events in inpatient
      settings. We conducted a retrospective case-control study of inpatient falls
      within aged care wards in a tertiary hospital to investigate the associated
      characteristics of elderly patients suffering from falls and fall-related
      characteristics. METHODS: Consecutive retrospective cross-sectional design
      spanned July 2006 to December 2008. PATIENT GROUP: Information on all aged care
      inpatients who suffered from 1 or more falls was extracted from Incident
      Information Management System (IIMS). Further details about the particular
      admission(s) were obtained from patients' medical records, e.g., patients'
      characteristics and circumstances surrounding the falls. Randomly selected aged
      care patients who did not suffer from a fall and who were discharged from the
      hospital in the same period served control group. Characteristics among patients
      with single fall and recurrent falls, as well as non-fallers were compared.
      RESULTS: Of the 438 falls evaluated, 71.9% occurred in patients' room and 18.9%
      in patients' bathroom/toilet. The common activities were moving/transferring and
      taking shower/toileting, respectively, 70.3%, 12.1% while occurring falls; and
      time of falls had a high peak during 9:00-11:00 a.m. Many were unassisted while
      falling. The common contributing factors for fall were intrinsic factors.
      Patients with recurrent falls were more likely to have lower Mini-Mental State
      Examination (MMSE) score. Logistic regression analysis showed length of stay
      longer than five weeks, dementia and stroke were independent risk factors for
      recurrent falls; and living in hostel/nursing home preadmission, needing
      assistance with mobility, cognitive impairment, stroke, incontinence and
      arthritis/osteoporosis were independent risk factors for fall. CONCLUSIONS: In an
      aged care ward, falls are independently associated with recurrent factors.
      Cognitive impairment/dementia was a strong risk factor for falls, and main causes
      leading to fall were intrinsic factors. For patients with cognitive
      impairment/dementia and behavioral disorder providing special and effective
      interventions is of paramount importance for reducing the incidence of fall in an
      aged care ward in hospital settings.

PMID- 20819627
TI  - Ningbo thyroid dysfunction prevalence study: a cross-sectional survey in an
      employees-cohort.
AB  - BACKGROUND: The prevalence and the spectrum of thyroid dysfunction in the
      mainland of China are not adequately understood. We performed a population-based
      study to determine the prevalence of major thyroid dysfunctions including overt
      and subclinical hyper- and hypothyroidism in a stable cohort. METHODS: All active
      and retired employees aged 20 years and older (11 067) of Sinopec Zhenhai
      Refining & Chemical Company in Ningbo participated in the cross-sectional survey
      with a questionnaire and blood samples. RESULTS: A total of 10 405 individuals
      attended for screening. Using biochemical definitions 95.5% were euthyroid. The
      prevalence of former diagnosed hyperthyroidism was 1.1% in females and 0.4% in
      males, hypothyroidism 1.7% and 0.3%, and thyroid surgery 1.2% and 0.3%,
      respectively. In both sex the prevalence increased with age. Twenty-four percent
      of individuals with thyroid surgery or medications had abnormal thyroid
      stimulating hormone (TSH) levels. In individuals without a history of thyroid
      disease, the prevalence of pathological TSH values in females and males were TSH
      > or = 10 mU/L 0.60% and 0.29%; TSH 4.8-9.9 mU/L 5.71% and 2.25%; TSH < 0.3 mU/L
      0.87% and 0.41%, respectively. Overt hyper- and hypothyroidism were uncommon
      (0.2%, 0.3%, respectively). The prevalence of subclinical hyper- and
      hypothyroidism was 0.4% and 3.4%, respectively. Subclinical hypothyroidism was
      more common in females (male 2.4% vs. female 5.8%, P < 0.001) and with increasing
      age (P < 0.001). CONCLUSIONS: The prevalence of thyroid dysfunction is 4.5% in
      the cohort. Among individuals with thyroid medications or surgery, only 75.7%
      were within the normal range of TSH. These results indicate that thyroid
      dysfunction is common in Chinese adults.

PMID- 20819628
TI  - Dynamic change of mother-source neutralizing antibodies against enterovirus 71
      and coxsackievirus A16 in infants.
AB  - BACKGROUND: Enterovirus 71 (EV71) and coxsackievirus A16 (Cox A16) are major
      causative agents for hand, foot and mouth disease (HFMD). Studies indicate that
      the frequent HFMD outbreaks result in a few hundreds children's death in China in
      recent years. The vaccine and other research for HFMD need to be developed
      urgently. THE AIMS OF OUR STUDY WERE: to explore dynamic development of mother
      source neutralizing antibodies against EV71 and Cox A16 in infants from Jiangsu
      Province, China, and to provide the fundamental data for further establishing of
      corresponding immunization course. METHODS: Peripheral blood samples were
      collected from 133 of parturient women once immediately before delivery and their
      infants at two and seven months of age. Method of micro-dose cytopathogenic
      effect was used to measure neutralizing antibodies against EV71 and Cox A16,
      respectively. RESULTS: Seropositive rates of anti-EV71 and anti-Cox A16 in
      prenatal women were 79.7% (106/133) and 92.5% (123/133), respectively; geometric
      mean titers (GMTs) were 29.0 and 61.9; 75.9% (101/133) prenatal women were both
      positive in anti-EV71 and anti-Cox A16; seropositive rates of anti-EV71 and anti
      Cox A16 were 25.6% (34/133) and 38.3% (51/133) in infants at two months of age;
      GMTs were 12.3 and 18.0, respectively. GMTs of anti-EV71 were significantly
      higher for infants at seven months (82.6) compared with that at two months (P <
      0.05), showing infants had inapparently infected by EV71 during two to seven
      months. Although only one offspring (0.75%) at seven months was found having anti
      Cox A16 transfered from maternal, this observation suggested no maternal antibody
      may remain in infants at seven months. CONCLUSIONS: The prevalence of EV71 and
      Cox A16 were relatively high in Jiangsu Province. Bivalent vaccine against both
      EV71 and Cox A16 should be developed, and the ideal time point for prime
      immunization for infants is around 2-5 months of age.

PMID- 20819629
TI  - Influence of drug treatment on glucocorticoid receptor levels in patients with
      coronary heart disease.
AB  - BACKGROUND: Glucocorticoid signaling exerts major roles in inflammation,
      metabolism and depression, which are three crucial factors accompanying or
      underlying coronary heart disease. Although accumulating evidence indicates the
      influence of glucocorticoids on the pathology and treatment of coronary heart
      disease, there is still a dearth of pharmaceutical mechanisms for this
      relationship. This study aimed to investigate the influence of drug treatment on
      glucocorticoid receptor levels in coronary heart disease. METHODS: Eighty
      hospitalized patients (average age (59.0 +/- 7.5) years, 46 male and 34 female)
      with coronary heart disease were categorized into four groups with 20 members in
      each according to one of the four drugs they were treated with. The four drugs
      were: nitrated derivative isosorbide dinitrate, the beta-adrenergic receptor
      blocker metoprolol, the calcium antagonist nifedipine, and the HMG-CoA reductase
      inhibitor lovastatin. Glucocorticoid receptor protein levels of peripheral blood
      lymphocytes were tested using immunoblotting analysis before and after one month
      of treatment. RESULTS: Immunoblotting analysis showed increased glucocorticoid
      receptor levels after treatment with metoprolol and nifedipine. There were no
      statistically significant changes of glucocorticoid receptor levels after
      treatment with isosorbide dinitrate or lovastatin, although there were trends of
      up-regulation of glucocorticoid receptor expression after both treatments.
      CONCLUSIONS: Both the beta-blocker and the calcium blocker can increase
      glucocorticoid receptor levels after chronic administration. This effect suggests
      a mechanism for their anti-inflammatory and other therapeutic roles for coronary
      heart disease and comorbid disorders.

PMID- 20819630
TI  - Early PET/CT after radiofrequency ablation in colorectal cancer liver metastases:
      is it useful?
AB  - BACKGROUND: Morphologic imaging after radiofrequency ablation (RFA) of liver
      metastases is hampered by an inflammatory response in the ablation margin, making
      the identification of local tumor progression (LTP) difficult. The aim of this
      study was to evaluate the efficacy of early (18)F-FDG PET/CT scanning to monitor
      the effectiveness of RFA in colorectal liver metastases. METHODS: Twelve patients
      with 20 metastases were treated with RFA for colorectal liver metastases. They
      underwent PET/CT within 2 weeks before RFA and within 24 hours after RFA (so
      termed "early PET/CT"). PET/CT was repeated at 1, 3, and 6 months, and then every
      6 months after ablation. The standard of reference was based on available
      clinical and radiological follow-up data. RESULTS: Early PET/CT revealed total
      photopenia in 16 RFA-treated metastases, which were found to be without residual
      tumor on the final PET/CT scan. Three RFA-treated metastases with focal uptake
      were identified as local tumor progression, which necessitated further treatment.
      One RFA-treated metastasis with rim-shaped uptake was regarded as inflammation.
      The results of the early PET/CT scanning were consistent with the findings of the
      final follow-up. CONCLUSIONS: PET/CT performed within 24 hours after RFA can
      effectively detect whether residual tumor exists for colorectal cancer liver
      metastases. The results can guide further treatment, and may improve the efficacy
      of RFA.

PMID- 20819631
TI  - A small-dose naloxone infusion alleviates nausea and sedation without impacting
      analgesia via intravenous tramadol.
AB  - BACKGROUND: Early studies showed that naloxone infusion decreases the incidence
      of morphine-related side effects from intravenous patient-controlled analgesia.
      This study aimed to determine whether naloxone preserved analgesia while
      minimizing side effects caused by intravenous tramadol administration. METHODS:
      Eighty patients undergoing general anesthesia for cervical vertebrae surgery were
      randomly divided into four groups. All patients received 1 mg/kg tramadol 30
      minutes before the end of surgery, followed by a continuous infusion with 0.3 mg
      x kg(-1) x h(-1) tramadol with no naloxone (group I, n = 20), 0.05 microg x kg(
      1) x h(-1) naloxone (group II, n = 20), 0.1 microg x kg(-1) x h(-1) naloxone
      (group III, n = 20) and 0.2 microg x kg(-1) x h(-1) naloxone (group IV, n = 20).
      Visual analog scales (VAS) for pain during rest and cough, nausea five-point
      scale (NFPS) for nausea and vomiting, and ramsay sedation score (RSS) for
      sedation were assessed at 2, 6, 12, 24 and 48 hours postoperatively. Analgesia
      and side effects were evaluated by blinded observers. RESULTS: Seventy-eight
      patients were included in this study. The intravenous tramadol administration
      provided the satisfied analgesia. There was no significant difference in either
      resting or coughing VAS scores among naloxone groups and control group. Compared
      with control group, sedation was less in groups II, III, and IV at 6, 12, and 24
      hours (P < 0.05); nausea was less in groups II, III and IV than group I at 2, 6,
      12, 24 and 48 hours postoperatively (P < 0.05). The incidence of vomiting in the
      control group was 35% vs. 10% for the highest dose naloxone group (group IV) (P <
      0.01). CONCLUSION: A small-dose naloxone infusion could reduce tramadol induced
      side effects without reversing its analgesic effects.

PMID- 20819632
TI  - Epidemiology of pterygium in aged rural population of Beijing, China.
AB  - BACKGROUND: Pterygium is a common ophthalmic disease and an important public
      health problem. It may be affected by many factors such as age, gender,
      ultraviolet radiation exposure, and time spent outdoors. This study aimed to
      investigate the prevalence of pterygium and evaluate the risk factors for the
      development of pterygium in the aged rural population of Beijing. METHODS: The
      investigation is a population-based cross-sectional study. Participants from 198
      villages of 13 suburban districts, aged 55 - 85 years old, were invited to
      complete a medical record, and 37 067 individuals were taken external ocular and
      fundus photos at Beijing ocular disease survey in 2008-2009. The information was
      uploaded by Internet and diagnosed with stages and grades by ophthalmological
      specialists. The prevalence, stages and grades of pterygia were observed.
      RESULTS: Of the 37 067 individuals, 1395 (3.76%) had pterygium. There was a
      significantly higher prevalence in male (5.13%) than in female (3.17%, P =
      0.000). The prevalence rate increased obviously with ages (chi(2) = 7.939, P =
      0.019) in rural Beijing. The average prevalence of 5.91% in Daxing and Fangshan
      districts with low latitude and low precipitation was significantly higher than
      that in Miyun and Huairou districts with high latitude and deep precipitation
      (3.17%, P = 0.000). The majority of the pterygia (43.5%) were in active stage and
      46.5% pterygia involved pupil area corneas. CONCLUSIONS: There is a statistically
      significant association between latitude and precipitation of habitation region
      and pterygium formation. Solar radiation, especially ultraviolet exposure
      represents a significant environment hazard to pterygium development.

PMID- 20819633
TI  - AKT-modified autologous intracoronary mesenchymal stem cells prevent remodeling
      and repair in swine infarcted myocardium.
AB  - BACKGROUND: Transplantation of adult bone marrow-derived mesenchymal stem cells
      (MSCs) has been proposed as a strategy for cardiac repair following myocardial
      damage. However cell transplantation strategies to replace lost myocardium are
      limited by the inability to deliver large numbers of cells that resist
      peritransplantation graft cell death. Accordingly, we set out to isolate and
      expand adult swine bone marrow-derived MSCs, and to engineer these cells to
      overexpress AKT1 (protein kinase B), to test the hypothesis that AKT1-engineered
      MSCs are more resistant to apoptosis and can enhance cardiac repair after
      transplantation into the ischemic swine heart. METHODS: The CDS (regulation
      domain of AKT1) AKT1-cDNA fragment was amplified, and MSCs were transfected
      following synthesis with a pCDH1-AKT1 shuttling plasmid. Western blotting
      analysis and real-time reverse transcription-polymerase chain reaction (RT-PCR)
      was performed. Myocardial infarction (MI) models were constructed in Meishan
      pigs, and cardiac function was evaluated by magnetic resonance imaging (MRI)
      measurements and echocardiography 4 weeks later. All pigs were assigned to four
      groups: control (A), DMEM (B), MSC (C), and AKT-transfected (D). MSCs were
      transfected with the AKT1 gene, and autologous BrdU-labeled stem cells (1 x
      10(7)/5 ml) were injected into left anterior descending coronary atery (LAD) of
      the infarct heart in groups C and D. In group B, DMEM was injected using the same
      approach. In group A, there was no injection following LAD occlusion. After 4
      weeks, cardiac function and regional perfusion measurements were repeated by MRI
      and echocardiography, and histological characteristics of the hearts were
      assessed. Connecxin-43 (CX-43), BrdU, and von Willebrand factor (VWF)
      immunoreactivity was tested using enzyme linked immunosorbent assay (ELISA).
      Vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF
      beta1) were analyzed at the same time. RESULTS: AKT1-cDNA was cloned into pCDH1
      MCS1-EF1-copGFP and the sequence was confirmed. AKT mRNA expression was detected
      at 24 hours after transfection. AKT1 expression in MSCs remained strong after 2
      weeks, according to real-time RT-PCR and Western blotting. Prior to cell
      implantation, end-diastolic left ventricular dimension (EDLVd) increased and
      stroke volume (SV) decreased in the MI hearts. MRI scans revealed significantly
      improved cardiac function following implantation, and implanted MSCs prevented
      thinning and expanding in the infarct region, as well as improved contraction and
      increased perfusion in all groups compared to control hearts. The left
      ventricular chamber size was smaller in cell-transplanted hearts than in control
      hearts. Moreover, group D exhibited significant improvement. The expression of CX
      43, BrdU, and VWF could be found in the immunohistochemical pathological sections
      of group C and group D. The level of VEGF reached a high level 1 week after
      implanting the MSCs, but the level of TGF-beta1 decreased gradually. CONCLUSIONS:
      The AKT1-expressing lentiviral vector resulted in stable over-expression of AKT1
      in MSCs. MSC engraftment in host myocardium improved cardiac function by
      attenuating contractile dysfunction and pathological thinning of the infracted
      left ventricular wall, which likely resulted from myocardial regeneration and
      angiogenesis.

PMID- 20819634
TI  - Cigarette smoke extract promotes proliferation of airway smooth muscle cells in
      asthmatic rats via regulating cyclin D1 expression.
AB  - BACKGROUND: Increased proliferation of airway smooth muscle cells (ASMCs) are
      observed in asthmatic patients and smoking can accelerate proliferation of ASMCs
      in asthma. To elucidate the molecular mechanisms leading to these changes, we
      studied in vitro the effect of cigarette smoke extract (CSE) on the proliferation
      of ASMCs and the expression of cyclin D1, an important regulatory protein
      implicated in cell cycle. METHODS: ASMCs cultured from 8 asthmatic Brown Norway
      rats were studied. Cells between passage 3 and 6 were used in the study and were
      divided into control group, pcDNA3.1 group, pcDNA3.1-antisense cyclin D1
      (ascyclin D1) group, CSE group, CSE + pcDNA3.1 group and CSE + pcDNA3.1-ascyclin
      D1 group based on the conditions for intervention. The proliferation of ASMCs was
      examined with cell cycle analysis, MTT colorimetric assay and proliferating cell
      nuclear antigen (PCNA) immunocytochemical staining. The expression of cyclin D1
      was detected by reverse transcriptase-PCR (RT-PCR) and Western blotting. RESULTS:
      (1) The percentage of S + G2M phase, absorbance value at 490 nm wavelength
      (A(490)) and the expression rate of PCNA protein in CSE group were (31.22 +/-
      1.17)%, 0.782 +/- 0.221, (90.2 +/- 7.0)% respectively, which were significantly
      increased compared with those of control group ((18.36 +/- 1.02)%, 0.521 +/-
      0.109, and (54.1 +/- 3.5)%, respectively) (P < 0.01). After the transfection with
      antisense cyclin D1 plasmid for 30 hours, the percentage of S + G2M phase, A(490)
      and the expression rate of PCNA protein in ASMCs were much lower than in
      untreated cells (P < 0.01). (2) The ratios of A(490) of cyclin D1 mRNA in CSE
      group was 0.288 +/- 0.034, which was significantly increased compared with that
      of control group (0.158 +/- 0.006) (P < 0.01). After the transfection with
      antisense cyclin D1 plasmid for 30 hours, the ratios of A(490) of cyclin D1 mRNA
      in ASMCs was much lower than in untreated cells (P < 0.01). (3) The ratios of
      A(490) of cyclin D1 protein expression in CSE group was 0.375 +/- 0.008, which
      was significantly increased compared with that of control group (0.268 +/- 0.004)
      (P < 0.01). After the transfection with antisense cyclin D1 plasmid for 30 hours,
      the ratios of A(490) of cyclin D1 protein expression in ASMCs was much lower than
      in untreated cells (P < 0.01). CONCLUSION: CSE may increase the proliferation of
      ASMCs in asthmatic rats via regulating cyclin D1 expression.

PMID- 20819635
TI  - Role of extracellular signal-regulated kinase in regulating expression of
      interleukin 13 in lymphocytes from an asthmatic rat model.
AB  - BACKGROUND: The extracellular signal-regulated kinase (ERK) is widely expressed
      in mammal cells and involved in airway proliferation and remodeling in asthma. In
      this study, we intend to explore the role of ERK in the expression of the Th2
      cytokine, interleukin 13 (IL-13) in lymphocytes in asthma. METHODS: Forty Sprague
      Dawley rats were randomly divided into two groups: normal control and asthmatic
      groups. Peripheral blood lymphocytes were isolated and purified from the blood of
      each rat and divided into five groups: control, asthmatic lymphocytes, asthmatic
      cells stimulated with ERK activator epidermal growth factor (EGF), or with ERK
      inhibitor PD98059, or with EGF and PD98059 together. The expression of
      phosphorylated-ERK (p-ERK) was observed by immunocytochemical staining, the
      expression of ERK mRNA was determined by reverse transcriptase-PCR, IL-13 protein
      in supernatants was measured by ELISA. RESULTS: (1) The ERK mRNA level and the
      percentage of cells with p-ERK in lymphocytes from asthmatic rats were
      significantly higher than those in normal controls, and were significantly
      increased by EGF administration. This effect of EGF was significantly inhibited
      by PD98059 pretreatment. (2) IL-13 protein in supernatants of asthmatic
      lymphocytes was higher than that produced by normal control lymphocytes, and was
      significantly increased by EGF treatment. This EGF effect was partly blocked by
      PD98059 pretreatment. (3) There was a significant positive correlation between
      the percentage of cells with p-ERK in peripheral blood lymphocytes and IL-13
      protein in supernatants of lymphocytes from asthmatic rats. CONCLUSIONS: In
      asthma the ERK expression and activation levels were increased, as was the
      protein level of IL-13. The ERK signaling pathway may be involved in the
      increased expression of the Th2 cytokine IL-13 in asthma.

PMID- 20819636
TI  - Inflammatory airway features and hypothalamic-pituitary-adrenal axis function in
      asthmatic rats combined with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Bronchial asthma (BA) and chronic obstructive pulmonary disease
      (COPD) are both inflammatory airway diseases with different characteristics.
      However, there are many patients who suffer from both BA and COPD. This study was
      to evaluate changes of inflammatory airway features and hypothalamic-pituitary
      adrenal (HPA) axis function in asthmatic rats combined with COPD. METHODS: Brown
      Norway (BN) rats were used to model the inflammatory airway diseases of BA, COPD
      and COPD + BA. These three models were compared and evaluated with respect to
      clinical symptoms, pulmonary histopathology, airway hyperresponsiveness (AHR),
      inflammatory cytokines and HPA axis function. RESULTS: The inflammatory airway
      features and HPA axis function in rats in the COPD + BA model group were greatly
      influenced. Rats in this model group showed features of the inflammatory diseases
      BA and COPD. The expression of inflammatory cytokines in this model group might
      be up or downregulated when both disease processes are present. The levels of
      corticotrophin releasing hormone mRNA and corticosterone in this model group were
      both significantly decreased than those in the control group (P < 0.05).
      CONCLUSIONS: BN rat can be used as an animal model of COPD + BA. By evaluating
      this animal model we found that the features of inflammation in rats in this
      model group seem to be exaggerated. The HPA axis functions in rats in this model
      group have been disturbed or impaired, which is prominent at the hypothalamic
      level.

PMID- 20819637
TI  - Effect of cholinesterase inhibitor galanthamine on circulating tumor necrosis
      factor alpha in rats with lipopolysaccharide-induced peritonitis.
AB  - BACKGROUND: The nervous system, through the vagus nerve and its neurotransmitter
      acetylcholine, can down-regulate the systemic inflammation in vivo, and recently,
      a role of brain cholinergic mechanisms in activating this cholinergic anti
      inflammatory pathway has been indicated. Galanthamine is a cholinesterase
      inhibitor and one of the centrally acting cholinergic agents available in clinic.
      This study aimed to evaluate the effect of galanthamine on circulating tumor
      necrosis factor alpha (TNF-alpha) in rats with lipopolysaccharide-induced
      peritonitis and the possible role of the vagus nerve in the action of
      galanthamine. METHODS: Rat models of lipopolysaccharide-induced peritonitis and
      bilateral cervical vagotomy were produced. In the experiment 1, the rats were
      randomly divided into control group, peritonitis group, and peritonitis groups
      treated with three dosages of galanthamine. In the experiment 2, the rats were
      randomly divided into sham group, sham plus peritonitis group, sham plus
      peritonitis group treated with galanthamine, vagotomy plus peritonitis group, and
      vagotomy plus peritonitis group treated with galanthamine. The levels of plasma
      TNF-alpha were determined in every group. RESULTS: The level of circulating TNF
      alpha was significantly increased in rats after intraperitoneal injection of
      endotoxin. Galanthamine treatment decreased the level of circulating TNF-alpha in
      rats with lipopolysaccharide-induced peritonitis, and there was significant
      difference compared with rats with lipopolysaccharide-induced peritonitis without
      treatment. The 3 mg/kg dosage of galanthamine had the most significant inhibition
      on circulating TNF-alpha level at all the three tested doses. Galanthamine
      obviously decreased the TNF-alpha level in rats with lipopolysaccharide-induced
      peritonitis with sham operation, but could not decrease the TNF-alpha level in
      rats with lipopolysaccharide-induced peritonitis with vagotomy. CONCLUSION:
      Cholinesterase inhibitor galanthamine has an inhibitory effect on TNF-alpha
      release in rats with lipopolysaccharide-induced peritonitis, and the vagus nerve
      plays a role in the process of the action of galanthamine.

PMID- 20819638
TI  - Up-regulation of the transient A-type K+ current (IA) in the differentiation of
      neural stem cells of the early postnatal rat hippocampus.
AB  - BACKGROUND: Neural stem cells (NSCs) not only are essential to cell replacement
      therapy and transplantation in clinical settings, but also provide a unique model
      for the research into neurogenesis and epigenesis. However, little attention has
      been paid to the electrophysiological characterization of NSC development. This
      work aimed to identify whether the morphological neuronal differentiation process
      in NSCs included changes in the electrophysiological properties of transient A
      type K(+) currents (I(A)). METHODS: NSCs were isolated from early postnatal rat
      hippocampus and were multiplied in basic serum-free medium containing basic
      fibroblast growth factor. Potassium currents were investigated and compared using
      whole-cell patch-clamp techniques and one-way analysis of variance (ANOVA),
      respectively. RESULTS: Compared with NSC-derived neurons, cloned NSCs (cNSCs) had
      a more positive resting membrane potential, a higher input resistance, and a
      lower membrane capacitance. Part of cNSCs and NSC-derived neurons possessed both
      delayed-rectifier K(+) currents (I(DR)) and I(A), steady-state activation of I(A)
      in cNSCs (half-maximal activation at (21.34 +/- 4.37) mV) occurred at a more
      positive voltage than in NSC-derived neurons at 1-6 days in vitro (half-maximal
      activation at (12.85 +/- 4.19) mV). CONCLUSIONS: Our research revealed a
      developmental up-regulation of the I(A) component during differentiation of
      postnatal NSCs. Together with the marked developmental up-regulation of I(DR) in
      vitro neuronal differentiation we have previously found, the voltage-gated
      potassium channels may participate in neuronal maturation process.

PMID- 20819639
TI  - Effects of buried penis on the structure and function of corpus cavernosum in a
      rat model.
AB  - BACKGROUND: While the abnormal appearance of the concealed penis has been well
      recognized, the effect of buried penis on the structure and function of corpus
      cavernosum has not been well studied. To explore this issue, we established a rat
      model and evaluated the effect of buried penis on cavernosum weight, contents and
      ultrastructure of tissue, and nitric oxide synthase (NOS) activity. METHODS: Two
      hundred and ten rats were randomly divided into 3 equal cohorts for 2, 4 and 6
      months study (groups A, B and C). Each group was randomly divided into buried
      group (n = 40), control group (n = 15), and normal group (n = 15), respectively.
      Intra-purse-string suture of the root of the penis was used to establish the
      model. Macroscopic development was judged by measuring the weight of the corpus
      cavernosum. Masson's trichrome staining was performed for observing
      microstructure while a transmission electron microscope was used for observing
      ultrastructure. The NOS activity was detected by a NOS activity assay kit.
      RESULTS: Buried penis had no significant influence on the appearance and weight
      of the corpus cavernosum. Buried penis resulted in decreased smooth muscle
      content (P > 0.05 in group A, and P < 0.05 in groups B and C) and increased
      fibrous connective tissue content (P > 0.05 in groups A and B, and P < 0.05 in
      group C) compared with the normal and control groups. Ultrastructural
      abnormalities of corpus cavernosum were observed in the 6-month buried group.
      Moreover, there was decrease of NOS activity in groups B and C (P < 0.05 in group
      B and P < 0.01 in group C) when compared with the normal and control groups.
      CONCLUSION: Buried penis affects the structure and function of corpus cavernosum
      in rats and the effect is positively correlated with the buried time, but there
      is no significant effect on the macroscopic development.

PMID- 20819640
TI  - Blood hibernation: a novel strategy to inhibit systemic inflammation and
      coagulation induced by cardiopulmonary bypass.
AB  - BACKGROUND: Inflammation and coagulation are two intimately cross-linked defense
      mechanisms of most, if not all organisms to injuries. During cardiopulmonary
      bypass (CPB), these two processes are activated and interact with each other
      through several common pathways, which may result in subsequent organ
      dysfunction. In the present study, we hypothesized that the addition of nitric
      oxide, prostaglandin E1 (PGE1), and aprotinin to the systemic circulation, hereby
      referred to as blood hibernation, would attenuate the inflammation and
      coagulation induced by CPB. METHODS: Thirty adult mongrel dogs were equally
      divided into five groups, anesthetized and placed on hypothermic CPB (32 degrees
      C). Each group received respectively the following treatments: (1) inhalation of
      40 ppm nitric oxide; (2) intravenous infusion of 20 ng x kg(-1) x min(-1) of
      PGE1; (3) 80,000 kallikrein inhibitor units (KIU)/kg of aprotinin; (4) the
      combination of all three agents (blood hibernation group); and (5) no treatment
      (control group) during CPB. Activation of leukocyte, platelet, endothelial cell,
      and formation of thrombin were assessed after CPB. RESULTS: As compared with the
      other four groups, leukocyte counts were higher, while plasma elastase,
      interleukin-8, CD11b mRNA expression, myeloperoxidase activities and lung tissue
      leukocyte counts were lower in the blood hibernation group (P < 0.05 versus other
      four groups after CPB). Plasma prothrombin fragment (PTF)1+2, and platelet
      activation factors were lower, while platelet counts were higher in the blood
      hibernation group (P < 0.05 versus other four groups at 6 and 12 hours after
      CPB). Electron microscopy showed endothelial pseudopods protrusion, with cell
      adherence in all four groups except the blood hibernation group where endothelial
      cells remained intact. CONCLUSION: Blood hibernation, effected by the addition of
      nitric oxide, PGE1 and aprotinin to the circulating blood during extra-corporeal
      circulation, was observed to attenuate the inflammation and coagulation induced
      by cardiopulmonary bypass, most likely by inhibiting the important common
      intermediates between the two cross-linked processes.

PMID- 20819641
TI  - Calcitonin gene-related peptide induces proliferation and monocyte
      chemoattractant protein-1 expression via extracellular signal-regulated kinase
      activation in rat osteoblasts.
AB  - BACKGROUND: Calcitonin gene-related peptide (CGRP), a sensory neuropeptide,
      affects osteoblast proliferation and bone formation. However, the mechanisms are
      not fully understood. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine
      that stimulates the migration of monocytes and plays important roles in
      regulating bone remolding during fracture repair. In this study, we investigated
      the effects of CGRP on proliferation and MCP-1 expression in cultured rat
      osteoblasts. METHODS: Primary rat osteoblasts were isolated from fetal rats
      calvariae. Cells were exposed to gradient concentrations (10(-9) to 10(-7) mol/L)
      of CGRP. Protein and mRNA levels of MCP-1 were quantified by Western blotting and
      semiquantitative reverse transcription-polymerase chain reaction, respectively.
      The protein level of MCP-1 was investigated and compared in cell culture media by
      enzyme linked immunosorbent assay (ELISA). Phospho-extracellular signal-regulated
      kinase (ERK) expression was detected by Western blotting. Cell proliferative
      activity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium
      bromide (MTT) and BrdU assay. The effects of MAPK/ERK kinase (MEK)-inhibitor
      U0126 on CGRP-induced MCP-1 expression in primary rat osteoblasts were examined.
      RESULTS: CGRP effectively enhanced primary rat osteoblast proliferation and led
      to significant increases in the expression of MCP-1 mRNA and protein in time- and
      dose-dependent manners. CGRP activated the ERK pathway. Pretreatment of cultured
      rat osteoblasts with MEK inhibitor U0126 resulted in dose-dependent inhibitions
      of CGRP-induced MCP-1 mRNA and protein levels. Thus, CGRP promoted cell
      proliferation and stimulated MCP-1 expression in cultured rat osteoblasts.
      CONCLUSION: These studies document novel links between CGRP and MCP-1 and
      illuminate the effects of CGRP in regulating bone remodeling.

PMID- 20819642
TI  - Activated vascular endothelia regulate invasion of glioma cells through
      expression of fibronectin.
AB  - BACKGROUND: Previous researches have indicated that glioma invasion may occur
      within a tumor-host microecology, and that fibronectin may be involved in glioma
      invasion as an important component of the extracellular matrix. However, how the
      interaction between tumor cells and vascular endothelial cells affects glioma
      invasion is poorly understood. The aim of this study was to investigate the
      effects of the interaction between tumor cells and vascular endothelial cells on
      glioma invasion, and the relationship of this interaction to fibronectin.
      METHODS: The localization of fibronectin in different brain astrocytoma tissues
      was determined by immunohistochemistry. Then, vascular endothelial cells and
      glioma cells were co-cultured in a Transwell co-culturing system. Fibronectin
      expression was detected by reverse transcriptase-polymerase chain reaction,
      immunocytochemistry, and enzyme-linked immunosorbent assay. Additionally, the
      influence of the interaction between tumor cells and vascular endothelial cells
      on glioma cell invasion was determined by an in vitro rapid invasion test.
      RESULTS: In brain astrocytoma tissues, fibronectin was present on the endothelial
      cells, in the extracellular matrix. Fibronectin expression was greater in higher
      grade tumors than in lower grade tumors. The interaction of glioma cells and
      vascular endothelial cells in vitro induced fibronectin release from vascular
      endothelial cells, which in turn stimulated glioma cell migration. This effect
      was inhibited by fibronectin blocking antibody. CONCLUSION: Glioma cells may
      induce vascular epithelial cells to express fibronectin, and in turn fibronectin
      could promote glioma cell invasion.

PMID- 20819643
TI  - Role of Toll-like receptor 4 and human defensin 5 in primary endocervical
      epithelial cells.
AB  - BACKGROUND: Endocervical epithelial cells play early roles in the defense of
      upper female genital tract to pathogens. Toll-like receptors (TLRs) and human
      defensins (HD) have recently been identified as fundamental components of the
      innate immune responses to bacterial pathogens. We aimed to use in vitro model of
      human primary endocervical epithelial cells (HPECs) to investigate their roles in
      innate immune response of the endocervix. METHODS: TLR4 expression and
      distribution in HPECs and endocervix were investigated by immunofluorescence
      (IF). Cultured HPECs were divided into lipopolysaccharide (LPS) group which were
      treated by LPS for 0, 24 and 48 hours, and control group without treatment. At
      each time point, the levels of HD5, IL-6 and TNF-alpha in supernants were
      determined by ELISA. TLR4 and HD5 expressions of cells were detected by Western
      blotting simultaneously. HD5 expression pattern was also compared between the
      HeLa cell line and HPECs. RESULTS: Endocervix tissue surface and HPECs expressed
      TLR4. After incubated with LPS, HPECs expressed significantly higher levels of
      TLR4 than control group, especially after 24 hours (P < 0.01), however decreased
      after 48 hours with a similar level of TLR4 expression compared with control
      group. LPS could upregulate the secretion of HD5, IL-6 and TNF-alpha in a time
      dependent manner (24 hours: P < 0.05; 48 hours: P < 0.01, compared with control
      group). Intracellular HD5 expression levels decreased over time. HD5 expression
      patterns in HPECs were different from HeLa cell line. CONCLUSIONS: To respond to
      LPS stimulation, HPECs may function in the mucosal immune defense through TLR4
      activation and HD5 secretion. HPEC is considered a significant model for
      immunological study.

PMID- 20819644
TI  - Arsenic trioxide up-regulates Fas expression in human osteosarcoma cells.
AB  - BACKGROUND: Osteosarcoma is a common primary malignant tumor of bone with a poor
      prognosis due to its propensity for metastasis. The prognosis of patients is
      highly dependent on the presence or absence of lung metastasis and on the
      effectiveness of treatment against it. It has been reported that low level
      expression of Fas protein in human osteosarcoma cell is closely associated with
      lung metastasis. A large number of studies have shown that arsenic trioxide (ATO)
      can inhibit proliferation and induce apoptosis of many cancer cell lines;
      however, its effects on human osteosarcoma cells (Saos-2 cell line) remains
      unknown. The aim of this study was to investigate the effects of ATO on Saos-2
      cells and to characterize its mechanism of Fas-expressing. METHODS: A group of
      Saos-2 cells was treated with or without 0.5, 1, 2, 4 and 8 micromol/L ATO for
      three successive days, and the cytotoxicity of ATO was determined by an 3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Morphological
      changes in cells were studied by acridine orange/ethidium bromide (AO/EB) double
      staining. Flow cytometry (FCM) was used to assay cell DNA distribution. Another
      group of cells was pretreated with 10 nmol/L matrix metalloproteinase 7 (MMP-7)
      for 3 hours. They were then incubated with or without 2 micromol/L ATO for 24, 48
      and 72 hours. Cytotoxicity, Fas protein and mRNA levels were systematically
      studied using MTT, Western blotting and real-time PCR, respectively. Cell
      proliferation, cell cycle progression and apoptosis were examined in this study.
      RESULTS: Proliferation of Saos-2 cells was inhibited by ATO in both a dose- and
      time-dependent manner. The IC(50) values at 24, 48 and 72 hours were 9.30, 5.54
      and 3.49 micromol/L, respectively. The survival rate of Saos-2 cells in the MMP-7
      and ATO co-treated group was significantly higher than the ATO group, but it was
      lower than the control group. ATO induced G(1) phase arrest of the cell cycle and
      very efficiently stimulated apoptosis in Saos-2 cells, as evidenced by flow
      cytometric detection of sub-G(1) DNA content and AO/EB staining. Western blotting
      results indicated that Fas (FasL) protein expression in osteosarcoma cultures
      markedly increases in a time dependent manner after exposure to ATO. Compared
      with control, treatment with ATO 2 micromol/L and 4 micromol/L for 48 hours,
      resulted in increase of Fas gene expression to 28.31% and 56.74%, respectively.
      Our results indicated that ATO induced-apoptosis of Saos-2 cells may be mediated
      through the Fas pathway. CONCLUSIONS: ATO suppressed cell proliferation of Saos-2
      cell in a dose- and time-dependent manner and increased Fas protein expression.
      However, Fas-mediated apoptosis was incompletely interrupted by MMP-7, which
      suggested that other molecular mechanisms may mediate this process.

PMID- 20819645
TI  - Safety and efficacy of transulnar approach for coronary angiography and
      intervention.
AB  - BACKGROUND: Transradial approach, which is now widely used in coronary
      angiography and intervention, may be advantageous with respect to the femoral
      access due to the lower incidence of vascular complications. Transulnar approach
      has been proposed for elective procedures in patients not suitable for
      transradial approach. The objective of this study was to evaluate the safety and
      efficacy of the transulnar approach versus the transradial approach for coronary
      angiography and intervention. METHODS: Two hundred and forty patients undergoing
      coronary angiography, followed or not by intervention, were randomized to
      transulnar (TUA) or transradial approach (TRA). Doppler ultrasound assessments of
      the forearm vessels were scheduled for all patients before procedures, 1 day and
      30 days after procedures. The primary end point was access site vascular
      complications during hospitalization and 30 days follow-up. Major adverse cardiac
      events (MACE) as secondary end point was recorded till 30 days follow-up.
      RESULTS: Successful puncture was achieved in 98.3% (118/120) of patients in the
      TUA group, and in 100% (120/120) of patients in the TRA group. Coronary
      angiographies were performed in 40 and 39 patients in TUA and TRA group.
      Intervention procedures were performed in 78 and 83 patients in TUA and TRA
      group, respectively. The incidence of artery stenosis 1 day and 30 days after
      procedures was 11.0% vs.12.3% and 5.1% vs. 6.6% in TUA and TRA group,
      respectively. Asymptomatic access site artery occlusion occurred in 5.1% vs.1.7%
      of patients 1 day and 30 days after transulnar angioplasty, and in 6.6% vs. 4.9%
      of patients 1 day and 30 days after transradial angioplasty. Minor bleeding was
      still observed at the moment of the ultrasound assessment in 5.9% and 5.7% of
      patients in TUA and TRA group, respectively (P = 0.949). No big forearm hematoma,
      and A-V fistula were observed in both groups. Freedom from MACE at 30 days follow
      up was observed in all patients. CONCLUSIONS: The transulnar approach is as safe
      and effective as the transradial approach for coronary angiography and
      intervention. It is an attractive opinion for experienced operators who are
      skilled in this technique, particularly in cases of anatomic variations of the
      radial artery, radial artery small-caliber or thin radial pulse.

PMID- 20819646
TI  - Increased hsp70 of glucocorticoid receptor complex induced by scald and heat
      stress and its possible effect on the affinity of glucocorticoid receptor.
AB  - BACKGROUND: Glucocorticoid (GC) insensitivity/GC resistance is an important
      etiological and prognostic factor in multiple diseases and pathophysiological
      processes such as scald, shock and asthma. The function of GC was mediated by
      glucocorticoid receptor (GR). Scald not only decreased the expression of GR but
      also reduced the affinity of GR, which played an important role in GC resistance
      in scalded rats. Whereas the molecular mechanism responsible for the decrease of
      GR affinity resulted from scald remains unclear. Recent studies showed that the
      changes of heat shock proteins (hsp) especially hsp90 and hsp70 of GR
      heterocomplex were associated with GR low affinity in vitro. METHODS: The
      affinity of GR in hepatic cytosols and in the cytosols of SMMC-7721 cells were
      determined by radioligand binding assay and scatchard plot. GR heterocomplex in
      cytosols were captured by coimmunoprecipation and the levels of hsp90 and hsp70
      of GR complex were detected by quantitative Western blotting. RESULTS: Similar
      with that of hepatic cytosol of scalded rats, a remarkable decrease of GR
      affinity was also found in the cytosol of heat stressed SMMC-7721 cells. The
      level of hsp70 of GR complex in hepatic cytosol of scalded rats (30% total body
      surface area immersion scald) and in cytosol of heat stressed human
      hepatocarcinoma cell line SMMC-7721 were both increased by 1.5 fold, whereas no
      change of hsp90 in GR heterocomplex was found. According to the correlation
      analysis, there may be a positive relationship between increased hsp70 of GR
      complex and decreased GR affinity in the cytosols. CONCLUSIONS: The primary
      results indicated that the level of hsp70 of GR heterocomplex was increased in
      the hepatic cytosol of scalded rats and the cytosol of heat stressed SMMC-7721
      cells. The increase of hsp70 of GR complex might be associated with the decrease
      of GR affinity.

PMID- 20819647
TI  - A new protein Girdin in tumor metastasis.

PMID- 20819648
TI  - Novel biomarkers for progression of chronic kidney disease.

PMID- 20819650
TI  - Globalized health and its governance.

PMID- 20819649
TI  - Protein causes hyperinsulinemia: a Chinese patient with
      hyperinsulinism/hyperammonaemia syndrome due to a glutamate dehydrogenase gene
      mutation.

PMID- 20819651
TI  - Preoperative preparation and surgical separation of conjoined pygopagus twins.

PMID- 20819652
TI  - Laparoscopic resection of an obturator schwannoma: a case report.

PMID- 20819653
TI  - Black hairy tongue associated with allo peripheral blood hematopoietic stem cell
      transplantation.

PMID- 20819654
TI  - Laparoscopic approach of Castleman's disease in the pararenal retroperitoneum:
      report of two cases.

PMID- 20819655
TI  - Brain motor control function in a patient with subacute, incomplete, asymmetrical
      spinal cord injury.

PMID- 20819656
TI  - Primary malignant melanoma of the lung in the elderly: case report and literature
      review.

PMID- 20819657
TI  - A giant primary myxoid liposarcoma of the posterior mediastinum.

PMID- 20819658
TI  - Surgical operation and re-operation for hepatocellular carcinoma with bile duct
      thrombosis.
AB  - BACKGROUND: Few reports have evaluated the efficacy of re-operation for relapse
      after initial surgery for hepatocellular carcinoma (HCC) with bile duct
      thrombosis (BDT). The aim of this study was to investigate the efficacy of
      initial surgery and subsequent re-operation for HCC with BDT, and their effects
      on prognosis. METHODS: The clinical data of 880 patients with HCC, including 28
      patients with BDT, who underwent radical hepatectomy between 1998 and 2008 in our
      hospital, were reviewed. The effects of BDT and re-operation on prognosis were
      retrospectively analyzed. RESULTS: The 1-, 3- and 5-year survival rates were
      89.3%, 46.4% and 21.4%, respectively, in 28 patients with BDT versus 91.4%, 52.9%
      and 20.9% in 852 patients without BDT (P>0.05). Six patients with BDT underwent
      re-operation after disease relapse, and their survival time was significantly
      longer than those who did not undergo re-operation (P<0.05). Multivariate
      analysis indicated that portal vein invasion and tumor size were independently
      associated with tumor relapse and prognosis (P<0.05). Univariate analysis and
      multivariate analyses showed that obstructive jaundice was not significantly
      correlated with tumor relapse or prognosis (P>0.05). CONCLUSIONS: Hepatectomy
      plus BDT removal is an effective treatment option for HCC with BDT. Obstructive
      jaundice is not a contraindication for surgery. Re-operation after relapse can
      provide good outcomes if the cases are appropriately selected.

PMID- 20819659
TI  - Coronary intervention in patients>or=75 years old with ST-elevation myocardial
      infarction: in-hospital and 6-month clinical outcomes.
AB  - BACKGROUND: ST-segment elevation myocardial infarction (STEMI) in elderly
      patients presents specific clinical characteristics. The study on percutaneous
      coronary intervention (PCI) in elderly patients (>or=75 years) with STEMI,
      however, has less been performed. METHODS: In the present study, 522 consecutive
      STEMI patients undergoing PCI within 12 hours from symptom onset were
      investigated, and clinical characteristics and in-hospital and 6-month outcomes
      of 66 elderly patients (>or=75 years, group A) were compared to those of 456
      younger patients (<75 years, group B). RESULTS: Compared to younger patients,
      elderly ones had more females (42.4% vs. 17.8%, P<0.005), a history of cerebral
      vascular events (7.6% vs. 0.9%, P<0.05), higher serum creatinine level ((96.48+/
      31.65) mmol/L vs. (84.87+/-19.81) mmol/L, P<0.005) and fewer smokers (28.8% vs.
      45.4%, P<0.05). The elderly ones had worse Killip class (Killip I class: 69.7%
      vs. 85.7%, P<0.05), less drug-eluting stent implantation and lower rates of TIMI
      flow 3 following PCI (33.3% vs. 47.1%, and 84.8% vs. 94.7%, P<0.05 respectively).
      Additionally, both in-hospital mortality and myocardial infarction rate were
      found to be higher in elderly patients (16.7% vs. 1.5%, and 7.6% vs. 2.6%, P<0.05
      respectively), which were also observed until 6-month follow-up (9.1% vs. 0, and
      6.1% vs. 0, P<0.05 respectively). In multivariable Cox regression analysis, serum
      creatinine level, history of hypertension, left anterior descending coronary
      artery as infarct-related artery and Killip class were independent predictors of
      6-month overall death in elderly patients. CONCLUSIONS: The clinical
      characteristics of elderly patients with STEMI after PCI are different from those
      of younger patients. Although PCI in this population is with a low rate of PCI
      failure, it is still associated with a worse outcome.

PMID- 20819660
TI  - Effect of interval after surgery on in vitro fertilization/ intracytoplasmic
      sperm injection outcomes in patients with stage III/IV endometriosis.
AB  - BACKGROUND: For patients with severe endometriosis, the spontaneous pregnancy
      rates have been reported to be near 0 due to extreme distortion of normal pelvic
      anatomy. Surgery is one of the treatment options; however, if patients failed to
      conceive after surgery, in vitro fertilization (IVF) is effective. The objective
      of this retrospective study was to determine the clinical characteristics of
      IVF/intracytoplasmic sperm injection (ICSI) in patients with stage III/IV
      endometriosis, and to determine the impact of the interval from surgery to
      IVF/ICSI on outcome. METHODS: One hundred and sixty patients who were diagnosed
      with stage III/IV endometriosis underwent IVF/ICSI cycles between February 2004
      and June 2009 were enrolled. The mean interval from surgery to IVF, number of
      oocytes retrieved, fertilization rate, implantation rate, embryos transferred,
      and good embryos transferred were compared between two age groups (<or=35 years
      and >35 years). RESULTS: The mean interval from surgery to IVF was (37.9+/-28.9)
      months for the group<or=35 years of age and (57.6+/-39.7) months for the group>35
      years of age. Twenty-five IVF/ICSI cycles (12.8%) were performed during the first
      year after surgery, and 34.9% IVF/ICSI cycles were performed 2 years after
      surgery. No significant differences existed between the two groups with respect
      to the fertilization rate, implantation rate, number of embryos transferred,
      number of good embryos, clinical pregnancy rates, live birth rates, and
      cumulative clinical pregnancy rates (P>0.05). The probability of cumulative
      clinical pregnancies was 75%, 50%, and 25% ((29.0+/-4.8), (61.0+/-7.6), and
      (120.0+/-16.9) months after surgery, respectively). CONCLUSIONS: For infertile
      patients with stage III/IV endometriosis, the optimal time to conceive by
      IVF/ICSI is <2 years after surgery; nevertheless, most of the patients took a
      longer time to conceive.

PMID- 20819661
TI  - Genetic analysis and serum level of cartilage oligomeric matrix protein in
      patients with pseudoachondroplasia.
AB  - BACKGROUND: Pseudoachondroplasia (PSACH) is an autosomal-dominant
      osteochondrodysplasia due to mutations in the gene encoding cartilage oligomeric
      matrix protein (COMP). Clinical diagnosis of PSACH is based primarily on family
      history, physical examination, and radiographic evaluation. There is evidence
      that decreased serum COMP concentration may serve as a diagnostic marker in
      PSACH. Here, we investigated the role of this gene and the serum COMP
      concentration in Chinese patients with PSACH. METHODS: A family with three
      patients and a sporadic case were recruited. Genomic and phenotypic data were
      recorded. The diagnosis of PSACH was made on the base of clinical evaluation. The
      genomic DNA was extracted from peripheral blood leukocytes. The 8-19 exons and
      flanking intron-exon boundary sequences of COMP were amplified by polymerase
      chain reaction (PCR) and screened for mutation by direct DNA sequencing. Serum
      COMP concentrations of 4 patients and age-compatible control group of 20
      unrelated healthy subjects were analyzed on the basis of an ELISA Kit for human
      cartilage oligomeric matrix protein. RESULTS: A deletion (c.1447-1455del) was
      identified in exon 13 in the sporadic case. The mean serum COMP concentrations of
      four patients (3.12+/-2.28) were significantly lower than those of control group
      (10.86+/-2.21, P<0.05). There was no overlap in the distribution of serum COMP
      concentration between PSACH patients and controls. CONCLUSIONS: Mutations in COMP
      gene are responsible for the PSACH. Serum COMP concentration may be suggested as
      an additional diagnostic marker to aid clinical findings in suspected cases of
      PSACH.

PMID- 20819662
TI  - Characteristics of abnormal menstrual cycle and polycystic ovary syndrome in
      community and hospital populations.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is considered to be the most common
      endocrine disorder in women of reproductive age. The involvement of an abnormal
      menstrual cycle in the etiology of PCOS remains unclear. We aimed to analyze the
      characteristics of abnormal menstrual cycles and their association with PCOS in
      community and hospital patient populations. METHODS: Women with PCOS identified
      from 2111 permanent female residents in the community of Beijing and 506
      outpatients obtained from the reproductive clinic of Peking University Third
      Hospital were recruited for this study, comprising the PCOS community group and
      the PCOS hospital group, respectively. Each group was further divided into four
      subgroups according to the length of menstrual cycles: <21 days; 21-34 days; 35
      60 days; and >60 days. Women in each group were interviewed using a questionnaire
      to assess factors including age, age of menarche, menstrual cycle history,
      related family history, and modified Ferriman-Gallwey (mF-G) score. All women
      received transvaginal ultrasound scan and had fasting blood samples taken for
      endocrine evaluation. A two-tailed P value of <0.05 was considered significant.
      RESULTS: In the community population, the prevalence of abnormal menstrual cycle
      was 27.19% (574/2111). The prevalence of PCOS in the community was 6.11%
      (129/2111) according to Rotterdam criteria. In the community group, the most
      common menstrual cycle length was 35-60 days, whereas for the hospital group, it
      was >60 days. In both the community and hospital groups, the most common
      phenotype of PCOS was that of Oligo/amenorrhea+PCO+ hyperandrogenism (HA) (O+P+H)
      (P=0.000). With increasing cycle length of 35-60 days to >60 days, the
      percentages of Oligo/amenorrhea+PCO (O+P) and O+P+H were found to significantly
      decrease in the community group and significantly increase in the hospital group
      (P=0.000 for each). In the hospital group, as the menstrual cycle length
      increased from 35-60 days to >60 days, the rate of spontaneous abortion increased
      significantly (P=0.000), meanwhile the rate of poorly-secreted endometrium and
      abnormal endometrial hyperplasia increased significantly (P=0.000). CONCLUSIONS:
      The prevalence of PCOS in the Beijing community of women was 6.11%.
      Oligo/amenorrhea was the most common type of abnormal menstrual cycle and may be
      an indicator for PCOS and endometrial lesions. Gynecologists should seek relevant
      medical information from women in the community to promptly diagnose PCOS and
      then follow up patients for potential development of subsequent complications.

PMID- 20819663
TI  - Increased expression of stathmin in eutopic endometrium of patients with
      endometriosis.
AB  - BACKGROUND: Stathmin was identified as an endometriosis-related protein by
      comparative proteomics in our previous study. As a microtubule-destabilizing
      factor, stathmin was shown to participate in the relay and integration of diverse
      intracellular signaling pathways involved in cell proliferation, differentiation,
      and many other cellular activities. To investigate whether stathmin is involved
      in the pathogenesis of endometriosis, we examined the expression of stathmin in
      eutopic endometrium of women with or without endometriosis. METHODS: Eutopic
      endometrium samples were collected from thirty-six patients who were diagnosed as
      endometriosis and the nineteen age-matched patients who were confirmed to be free
      of endometriosis surgically and histologically. The expression of stathmin mRNA
      was detected by real-time PCR, and its protein was detected by Western blotting
      and immunohistochemistry. RESULTS: Stathmin was overexpressed in eutopic
      endometrium of women with endometriosis detected by real-time PCR in mRNA levels
      and by Western blotting in protein levels, without significant difference between
      proliferative and secretory phase. Immunohistochemistry showed that stathmin
      protein was localized in both endometrial glandular and stromal cells throughout
      the menstrual cycle. CONCLUSIONS: Stathmin is overexpressed in endometrium of
      patients with endometriosis and may play a role in the pathogenesis of
      endometriosis.

PMID- 20819664
TI  - The outcome after using two different approaches for excision of Morton's
      neuroma.
AB  - BACKGROUND: The choice for the surgical approach of interdigital neuroma in the
      foot is controversial. Plantar approach can leave a painful scar on weight
      bearing area; hence, some prefer dorsal approach. The aim of the current study
      was to measure the outcome of interdigital (Morton's) neurectomy performed by a
      single surgeon using dorsal and plantar approaches. METHODS: A retrospective
      review of the patient records of one orthopaedic foot and ankle surgeon
      identified thirty-six patients (42 feet) who had been treated operatively for a
      primary, persistently painful interdigital neuroma. The mean follow-up was 18
      months. Pain, weight bearing, wound problems and rehabilitation period were
      studied. RESULTS: The duration to full weight bearing, return to work, driving
      and recreational activities were at least one week shorter in the dorsal group.
      The overall satisfaction for surgery was rated as excellent or good in 85% of the
      thirty six patients. Scar problems were more troublesome and common in the
      plantar group. There was residual numbness noticed in twenty feet, the pattern of
      numbness was quite variable and it was bothersome in only seven feet. There was
      one recurrence in the plantar group. CONCLUSIONS: Resection of a symptomatic
      interdigital neuroma through a dorsal or a plantar approach can result in a good
      outcome. Dorsal approach, however, is associated with better rehabilitation and
      less scar problems.

PMID- 20819665
TI  - Valganciclovir for pre-emptive therapy of cytomegalovirus viraemia after
      hematopoietic stem cell transplantation: a prospective multi-center trial.
AB  - BACKGROUND: Despite its widespread use in the management of HIV-related
      cytomegalovirus (CMV) infection, there have been surprisingly few reports of the
      use of valganciclovir (VGC) in the post-allotransplant setting. So far, no multi
      center, non-crossover trial data have been available with the use of this drug as
      the primary pre-emptive. The present study evaluated the efficacy and safety of
      VGC for preemptive therapy of CMV infection after allogeneic hematopoietic stem
      cell transplantation (HSCT). METHODS: From January to April 2007, VGC was adopted
      in eleven centers in mainland China for pre-emptive therapy of CMV infection in
      consecutive patients undergoing allogeneic HSCT. Allogeneic HSCT recipients were
      followed weekly via CMV pp65 antigenemia assay or real-time quantitative
      polymerase chain reaction (PCR) for detection of CMV-DNA. Patients with a
      positive assay were treated with VGC, 900 mg P.O. twice a day for 14 days
      followed by 900 mg P.O. once a day for 14 days after a negative result or the CMV
      DNA load was lower. RESULTS: A total of 54 patients (15 siblings, 28 mismatched
      related donors, 11 unrelated donors) had a positive assay treated with oral VGC.
      The seroconversion rate was 89% (48/54) as confirmed by a negative assay; six
      patients failed oral VGC. No significant toxicity was encountered. No case of CMV
      disease was diagnosed in the responding patients with a median follow-up of 5.3
      months after the drug administration. CONCLUSION: Pre-emptive therapy of CMV
      viraemia with oral VGC is safe and effective in allogeneic HSCT.

PMID- 20819666
TI  - Virtual reality system for diagnosis and therapeutic planning of cerebral
      aneurysms.
AB  - BACKGROUND: The virtual reality (VR) system can provide the neurosurgeon to
      intuitively interact with and manipulate the three dimensional (3-D) image
      similarly to manipulate a real object. It was seldom reported that the system was
      used in diagnosis and treatment of cerebral aneurysms. This study aimed to
      investigate the application of VR system in diagnosis and therapeutic planning of
      cerebral aneurysms. METHODS: A total of 24 cases of cerebral aneurysms were
      enrolled in this study from 2006 to 2008, which diagnosed by 3-D digital
      subtraction angiography (3D-DSA) or VR-based computed tomography angiographies
      (CTA). The VR system and 3D-DSA system were used to observe and measure aneurysms
      and the adjacent vessels. The data of observation and measurements were compared
      between VR image and 3D-DSA image. All the patients underwent surgical plan and
      simulated neurosurgical procedures in the VR system. RESULTS: There were 28
      aneurysms detected in VR system and 3D-DSA system. The VR system generated clear
      and vivid 3-D virtual images which clearly displayed the location and size of the
      aneurysms and their precise anatomical spatial relations to the parent arteries
      and skull. The location, size and shape of the aneurysms and their anatomical
      relationship with the adjacent vessels were similar between 3-D virtual image and
      3D-DSA, but the spatial relationship between aneurysms and skull only been
      displayed by VR system. This VR system also could simulate simple surgical
      procedures and surgical environments. CONCLUSIONS: The VR system can provide a
      highly effective way to provide precise imaging details as same as 3D-DSA system
      and assist the diagnosis of cerebral aneurysms with virtual 3-D data based on
      CTA. It significantly enhances the chosen therapeutic strategy of cerebral
      aneurysms.

PMID- 20819667
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration of undiagnosed
      mediastinal lymphadenopathy.
AB  - BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration
      (EBUS-TBNA) can sample the enlarged mediastinal lymph nodes which are unreachable
      by conventional bronchoscopy. It is a relatively simple and safe method to see
      beyond the bronchial tree. We describe and discuss its initial application and
      our experience. METHODS: From July 2009 to December 2009, 52 patients with
      undiagnosed enlarged mediastinal lymph nodes were accessed with EBUS-TBNA in the
      People's Liberation Army General Hospital. Conventional bronchoscopy was
      performed before EBUS-TBNA, and patients with endobronchial lesions were excluded
      from this study. Smears fixed in 95% alcohol and histological specimens fixed in
      formalin were sent to Department of Pathology. RESULTS: EBUS-TBNA was diagnostic
      in 33 (63%) patients, with diagnosis of lung cancer in 23 patients (14 patients
      of small cell lung cancer, eight patients with adenocarcinoma, and one patient of
      squamous carcinoma). Four patients, who had negative EBUS-TBNA results, were
      later diagnosed with malignancy at thoracotomy. One patient with negative EBUS
      TBNA results died of cancer cachexia. The sensitivity, specificity, and positive
      and negative predictive value of EBUS-TBNA for the diagnosis of neoplastic
      disease were 85%, 100%, 100%, and 50% respectively. Among the 16 sarcoidosis
      patients, who were diagnosed by a combination of the clinical and radiological
      information as well as pathological results obtained by EBUS-TBNA, nine of them
      had granulomas and benign lymphoid cells detected by EBUS-TBNA. The sensitivity,
      specificity, and positive and negative predictive value of EBUS-TBNA for the
      diagnosis of sarcoidosis were 56%, 100%, 100%, and 13%, respectively. Five
      patients with no definite diagnosis from EBUS-TNBA examination are under close
      follow-up. CONCLUSIONS: EBUS-TBNA can provide a safe and effective method to
      sample mediastinal leisions suspected of malignancy. It also adds pathological
      information needed to make the diagnosis of sarcoidosis.

PMID- 20819668
TI  - Up-regulation of the expression of S100A8 and S100A9 in lung adenocarcinoma and
      its correlation with inflammation and other clinical features.
AB  - BACKGROUND: S100A8 and S100A9 are two members of the S100 protein family
      characterized by the presence of two Ca2+-binding sites of the EF-hand type.
      Previous studies suggested that the whole S100 family displays significant
      functions in tumor growth, progression and invasion. This study aimed to
      determine the expression of the two indices of the family, S100A8 and S100A9, in
      lung cancer tissues and normal lung tissues and its correlation with clinical
      features. METHODS: A total of 60 cases with a variety of clinical data that were
      diagnosed with different histological subtypes of lung cancer were investigated.
      Semi-quantitative reverse transcriptase-PCR (Sq-Rt-PCR) and immunohistochemical
      staining of cancer, adjacent and peripheral lung tissues were executed to
      distinguish the expression patterns of S100A8 and S100A9 and to further clarify
      their correlation with clinical features. RESULTS: Immunohistochemical staining
      of both proteins showed a significant up-regulation in lung cancer tissue
      (S100A8, S100A9, P<0.0001), and PCR revealed that the levels of S100A8 and S100A9
      expression were significantly higher in lung cancer tissues (S100A8
      P=0.002/0.004; S100A9 P=0.022/0.026). The higher expression was found to be
      correlated with the clinical characteristics of adenocarcinoma, inflammation and
      stage IV lesion. CONCLUSIONS: S100A8, S100A9 up-regulation was found in the lung
      adenocarcinoma and end stage lung cancer tissue, the correlation of which with
      their higher expression in inflammatory lung tissues may indicate the
      collaborative effect of inflammation on the progression of cancer.

PMID- 20819669
TI  - Vision, subjective accommodation and lens mobility after TetraFlex accommodative
      intraocular lens implantation.
AB  - BACKGROUND: The TetraFlex accommodating intraocular lens (IOL) was designed to
      supply the patients both satisfied far and near vision after cataract surgery. So
      we need to evaluate the safety, distance and near visual acuity, subjective
      accommodation and IOL mobility with the TetraFlex accommodating IOL implantation.
      METHODS: Fifty eyes of 42 study-eligible cataract patients, who gave informed
      consent at a single eye clinic in China over a 10-month period, underwent
      phacoemulsification with TetraFlex IOL implantation. At three months
      postoperation, uncorrected visual acuities (UCVA), best corrected visual acuities
      (BCVA), distance-corrected near visual acuities (DCNVA), subjective accommodation
      using the defocus method, and pilocarpine-induced IOL mobility were measured.
      RESULTS: No postoperative complications were noted in the study. Three months
      postoperation UCVA and BCVA were 20/40 or bettter in 82% (41/50) and 92% (46/50)
      of eyes, respectively; 66% (33/50) of the eyes had DCNVA of Jager (J) 4 or better
      at 3 months. In addition, the mean subjective accommodation was (0.94+/-0.61)
      diopters (D) (range from 0.50 to 1.50 D) and pilocarpine-induced IOL mobility was
      (337+/-124) microm (range from 121 to 501 microm) with the TetraFlex. High
      relationship (r2=0.901, P<0.01) was found between these two measurements.
      CONCLUSION: Implantation of the TetraFlex is safe and leads to excellent
      uncorrected distance vision and good uncorrected near vision.

PMID- 20819670
TI  - Expression of soluble Toll-like receptors in pleural effusions.
AB  - BACKGROUND: The Toll-like receptors (TLRs) represent a group of single-pass
      transmembrane receptors expressed on sentinel cells that are central to innate
      immune responses.The aim of this study was to investigate the presence of soluble
      TLRs in pleural effusions, and the diagnostic values of TLRs for pleural effusion
      with various etiologies. METHODS: Pleural effusion and serum samples were
      collected from 102 patients (36 with malignant pleural effusion, 36 with
      tuberculous pleural effusion, 18 with bacterial pleural effusion, and 12 with
      transudative pleural effusion). The concentrations of TLR1 to TLR10 were
      determined in effusion and serum samples by enzyme linked immunosorbent assay.
      Four classical parameters (protein, lactate dehydrogenase, glucose and C-reactive
      protein (CRP)) in the pleural fluid were also assessed. Receiver-operating
      characteristic curves were used to assess the sensitivity and specificity of
      pleural fluid TLRs and biochemical parameters for differentiating bacterial
      pleural effusion. RESULTS: The concentrations of TLR1, TLR3, TLR4, TLR7 and TLR9
      in bacterial pleural effusion were significantly higher than those in malignant,
      tuberculous, and transudative groups, respectively. Analysis of receiver
      operating characteristic curves revealed that the area under the curves of TLR1,
      TLR3, TLR4, TLR7 and TLR9 were 0.831, 0.843, 0.842, 0.883 and 0.786,
      respectively, suggesting that these TLRs play a role in the diagnosis of
      bacterial pleural effusion. Also, the diagnostic value of TLRs for bacterial
      pleural effusions was much better than that of biochemical parameters (protein,
      lactate dehydrogenase, glucose and CRP). CONCLUSIONS: The concentrations of TLR1,
      TLR3, TLR4, TLR7 and TLR9 appeared to be increased in bacterial pleural effusion
      compared to non-bacterial pleural effusions. Determination of these pleural TLRs
      may improve the ability of clinicians to differentiate pleural effusion patients
      of bacterial origin from those with other etiologies.

PMID- 20819671
TI  - Effect of lycopene on androgen receptor and prostate-specific antigen velocity.
AB  - BACKGROUND: There is increasing interest in the role of dietary factors in both
      the development and behaviour of prostate cancer. This study was carried out to
      evaluate the impact of the dietary factor lycopene on DNA synthesis, activity and
      expression of the androgen receptor gene element in prostate LnCaP cells and to
      report our pilot phase II study investigating its effect on prostate-specific
      antigen velocity over one year. METHODS: LnCaP cells were grown with or without
      different concentrations of lycopene or tetrahydrofuran (THF solvent) added to
      the culture medium for 48 hours. DNA synthesis was measured by the incorporation
      of bromodeoxyuridine (Brdu) into DNA during a 4-hour pulse, followed by
      immunostaining and visualization of stained cells using fluorescence microscopy.
      A transient transfection of a plasmid DNA recombinant containing an androgen
      receptor element-luciferase (ARE-Luc) report gene into LnCaP cells was developed
      and the impact of different concentrations of lycopene on the androgen receptor
      element was reflected by quantitative analysis of the luciferase enzyme function.
      Expression of the androgen gene was also studied by Western blotting. The phase
      II pilot study patients (n=41) previously diagnosed with prostate cancer were
      enrolled and given lycopene supplement, 10 mg per day, and response was measured
      by observing changes in the plasma prostate-specific antigen (PSA) levels.
      RESULTS: The addition of 0.5 micromol/L, 5 micromol/L, 10 micromol/L and 15
      micromol/L of lycopene was shown to inhibit cell growth by 2.66%, 4.29%, 3.73%
      and 13.66%, respectively, compared with the THF solvent control samples
      (P=0.015). As compared with the RPMI1640 medium group, cell proliferation in the
      presence of 5 micromol/L, 10 micromol/L, and 15 micromol/L lycopene was inhibited
      by 8.12%, 6.33% and 12.00%, respectively (P=0.024). We showed for the first time
      that lycopene inhibited the activity of the androgen receptor gene element in a
      dose-related manner. Inhibition was seen in the transcription of the luciferase
      construct and confirmed by androgen receptor element expression assayed by
      Western blotting. Regression slopes of (log) PSA vs. time decreased in 26/37
      (70%, 95%CI 53%-84%) of the patients after supplementation and in eight cases
      (21%) the post-treatment slope was negative. For these eight patients, the
      average fall in PSA was equivalent to 2% over 28 days (i.e. an average slope/d of
      -0.000713). The Wilcoxon rank-sum test showed an overall statistically
      significant decrease in slope (P=0.0007). Analysis of the PSA doubling time
      (pretreatment vs. posttreatment) showed a median increase after supplementation
      for 174 days; however, this was not statistically significant (P=0.18).
      CONCLUSIONS: Lycopene as an antioxidant dietary factor could significantly
      inhibit DNA synthesis in a dose-dependent pattern; the result revealed lycopene
      might inhibit androgen receptor gene element activity and expression. Dietary
      lycopene may play an important role in prostate cancer cell proliferation and
      further supports a large randomized study into the role of lycopene
      supplementation in malignant prostate disease.

PMID- 20819672
TI  - Lamin C protein deficiency in the primary fibroblasts from a new laminopathy case
      with ovarian cystadenoma.
AB  - BACKGROUND: Laminopathies are a group of rare genetic disorders characterized by
      multiple-tissue degeneration. We describe a new laminopathy with ovarian
      cystadenoma and explore its molecular etiology. METHODS: The case is a 15-year
      old girl who presents the prominent progeroid disorders, multiple system
      degeneration and early-onset cystadenoma of the ovary. Candidate genes including
      LMNA, ZMPSTE24, PPAR G, INSR and WRN were sequenced to screen for DNA variants.
      The mRNA and protein expression levels of LMNA were examined in primary
      fibroblasts. The pathophysiological events such as morphologic alterations, cell
      senescence, cell proliferation, apoptosis and pRb as well as p53 protein
      expressions were also investigated in primary fibroblasts. RESULTS: No mutation
      was identified in the candidate genes screened. Nuclear abnormalities including
      nuclear blebs, mislocalization of lamin A/C were evident in the patient
      fibroblasts. Ultrastructurally, nucleus exhibited nuclear herniation and almost
      complete loss of peripheral heterochromatin. In addition, lamin C protein
      expression was markedly reduced whereas lamin A protein level was normal and no
      prelamin A was detected in the primary fibroblasts. Although the senescence
      associated beta-galactosidase staining of patient' cells was negative, cells in S
      phase increased in accompany with a decrease in pRb protein expression.
      Furthermore, increases in apoptotic cell death and p53 expression were observed.
      CONCLUSIONS: Our data suggest that selective deficiency of lamin C protein is
      associated with a case of laminopathy with ovarian cystadenoma. The abnormalities
      in nuclear structure and alterations in gene expression such as the decrease in
      pRb and increase in p53 may be responsible for the multiple tissue degeneration.

PMID- 20819673
TI  - Eliminating impingement optimizes patellar biomechanics in high knee flexion.
AB  - BACKGROUND: We investigated the impact of eliminating the impingement between
      extensor mechanism and tibial insert on patellar tracking and patellar ligament
      tension in high knee flexion. METHODS: Six cadaveric specimens were tested on an
      Oxford-type testing rig. The Genesis II knee system was implanted into each
      specimen knee with the traditional tibial insert and high-flex insert
      successively. Compared to traditional insert, the high-flex insert was
      characterized with a chambered anterior post and a chambered anterior lip which
      eliminates patella-post and patellar ligament-anterior lip impingements. The
      patella was tracked with an NDI Optotrak Certus system. The patellar ligament
      tension was measured using a NKB S-type tension transducer. RESULTS: There was a
      decrease of resultant patellar translation relative to the femur with
      statistically significant (P<0.05) at 90 degrees to 150 degrees of knee flexion
      and a decrease of patellar ligament tension with statistical significance
      (P<0.05) at 100 degrees, 120 degrees, 130 degrees, and 140 degrees of flexion
      using high-flex insert compared to traditional insert. CONCLUSIONS: Eliminating
      the impingement between extensor mechanism and implant in high knee flexion
      altered patellar tracking and reduced patellar ligament tension, which would
      facilitate high knee flexion.

PMID- 20819674
TI  - Changes in genioglossus and their association with serum adiponectin levels in
      rats subjected to chronic intermittent hypoxia.
AB  - BACKGROUND: The genioglossus (GG) is involved in the maintenance of an open
      airway for effective breathing. Although the pathogenesis of obstructive sleep
      apnea hypopnea syndrome (OSAHS) was closely associated with GG dysfunction, its
      causes and possible treatment have not been elucidated. The aim of the study was
      to investigate the effects of chronic intermittent hypoxia (CIH) on serum
      adiponectin levels, electromyograph (EMG) activity and ultrastructure of GG, as
      well as the effect of an adiponectin supplement in anesthetized rats. METHODS:
      Forty-two healthy male Wistar rats were randomly divided into normal control (A),
      CIH (B) and adiponectin treatment (C) groups, 14 rats in each group. CIH was
      performed eight hours per day for five weeks in both groups B and C. Group C
      received transvenous injection of adiponectin at the dosage of 10 microg per
      injection, twice a week for five weeks. At the end of the 5th week the GG EMG
      voltage was measured and compared among the three groups. Transmission electron
      microscope was used to observe the ultrastructure of the GG. RESULTS: CIH caused
      significant hypoadiponectinemia, weakened activity of GG EMG at both baseline and
      hypoxia stimulation, and induced ultrastructural pathological changes, such as,
      myofibril discontinuities, lysis of myofilament, edema of mitochondria and
      disruption of cristae, vacuolus and lysis of some mitochondria. Venous supplement
      of adiponectin improved the above pathological changes resulting from CIH.
      CONCLUSION: CIH resulted in pathological changes in GG's EMG and ultrastructure,
      which could be improved by supplement of adiponectin and be associated with
      hypoadiponectinemia caused by CIH.

PMID- 20819675
TI  - Effects of therapeutic hypercapnia on inflammation and apoptosis after hepatic
      ischemia-reperfusion injury in rats.
AB  - BACKGROUND: Therapeutic hypercapnia (TH) has been demonstrated to protect several
      organs ischemia-reperfusion injury. The study aimed to investigate the effects of
      therapeutic hypercapnia on hepatic ischemia-reperfusion injury (HIRI). METHODS:
      Thirty adult male Wistar rats weighing (250+/-20) g were randomized into 3 groups
      (n=10 in each), group C (control group), group A (hypercapnia group) and group B
      (CO2 preconditioning group). A segmental ischemia of the liver was induced by
      interrupting the blood vessels including the bile duct to the median and left
      lateral lobes for 60 minutes and all the animals were sacrificed after 240
      minutes observation period of reperfusion. Mean arterial pressure (MAP) and the
      blood gases were measured before ischemia (baseline) and at 30, 60, 120, 180 and
      240 minutes after reperfusion. Arterial blood samples were obtained for
      determination of serum levels of TNF-alpha, IL-10, serum aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT). The histopathology of
      liver tissues was evaluated by light microscopy. The NF-kappaB expression and
      apoptotic hepatocytes were respectively determined by immunohistochemistry and
      TUNEL assay. RESULTS: The serum levels of liver enzymes and TNF-alpha were
      significantly decreased while the IL-10 level was significantly increased in
      groups A and B than in group C (P<0.05), and group B surpassed group A (P<0.05).
      The histopathological scores, the NF-kappaB immunohistochemical score (IHS) and
      apoptotic index were significantly lower in groups A and B than in group C
      (P<0.05), and the decrease in group B was more obvious than in group A (P<0.05).
      CONCLUSION: Therapeutic hypercapnia attenuates ischemia-reperfusion injury to the
      liver. Moreover, the effects of CO2 preconditioning are outstandingly notable.

PMID- 20819676
TI  - Gefitinib attenuates murine pulmonary fibrosis induced by bleomycin.
AB  - BACKGROUND: Gefitinib, an inhibitor of epidermal growth factor receptor (EGFR)
      tyrosine kinase, is an effective treatment for epithelial tumors, including non
      small cell lung cancer (NSCLC), and is generally well tolerated. However, some
      clinical trials revealed that gefitinib exposure caused lung fibrosis, a severe
      adverse reaction. This study investigated the effect of gefitinib on lung
      fibrosis in mice. METHODS: We generated a mouse model of lung fibrosis induced by
      bleomycin to investigate the fibrotic effect of gefitinib. C57BL/6 mice were
      injected intratracheally with bleomycin or saline, with intragastric
      administration of gefitinib or saline. Lung tissues were harvested on day 14 or
      21 for histology and genetic analysis. RESULTS: The histological results showed
      that bleomycin successfully induced lung fibrosis in mice, and gefitinib
      prevented lung fibrosis and suppressed the proliferation of S100A4-positive
      fibroblast cells. In addition, Western blotting analysis revealed that gefitinib
      decreased the expression of phosphorylated EGFR (p-EGFR). Furthermore,
      quantitative real-time PCR (qRT-PCR) demonstrated that gefitinib inhibited the
      accumulation of collagens I and III. CONCLUSIONS: These results reveal that
      gefitinib reduces pulmonary fibrosis induced by bleomycin in mice and suggest
      that administration of small molecule EGFR tyrosine kinase inhibitors has the
      potential to prevent pulmonary fibrosis by inhibiting the proliferation of
      mesenchymal cells, and that targeting tyrosine kinase receptors might be useful
      for the treatment of pulmonary fibrosis in humans.

PMID- 20819677
TI  - Auto-mobilized adult hematopoietic stem cells advance neovasculature in diabetic
      retinopathy of mice.
AB  - BACKGROUND: Hematopoietic stem cells (HSCs) can be used to deliver functionally
      active angiostatic molecules to the retinal vasculature by targeting active
      astrocytes and may be useful in targeting pre-angiogenic retinal lesions. We
      sought to determine whether HSC mobilization can ameliorate early diabetic
      retinopathy in mice. METHODS: Mice were devided into four groups: normal mice
      control group, normal mice HSC-mobilized group, diabetic mice control group and
      diabetic mice HSC mobilized group. Murine stem cell growth factor (murine SCF)
      and recombined human granulocyte colony stimulating factor (rhG-csf) were
      administered to the mice with diabetes and without diabetes for continuous 5 days
      to induce autologous HSCs mobilization, and subcutaneous injection of
      physiological saline was used as control. Immunohistochemical double staining was
      conducted with anti-mouse rat CD31 monoclonal antibody and anti-BrdU rat
      antibody. RESULTS: Marked HSCs clearly increased after SCF plus G-csf
      mobilization. Non-mobilized diabetic mice showed more HSCs than normal mice
      (P=0.032), and peripheral blood significantly increased in both diabetic and
      normal mice (P=0.000). Diabetic mice showed more CD31 positive capillary vessels
      (P=0.000) and accelerated endothelial cell regeneration. Only diabetic HSC
      mobilized mice expressed both BrdU and CD31 antigens in the endothelial cells of
      new capillaries. CONCLUSION: Auto-mobilized adult hematopoietic stem cells
      advance neovasculature in diabetic retinopathy of mice.

PMID- 20819678
TI  - Effects of eukaryotic expression plasmid encoding human tumstatin gene on
      endothelial cells in vitro.
AB  - BACKGROUND: Tumstatin is a novel endogenous angiogenesis inhibitor which is
      widely studied using purified protein. The current study evaluates the
      antiangiogenic effects of tumstatin-overexpression plasmid in vitro, reveals the
      mechanism underlying the vascular endothelial cell growth inhibition and searches
      for a novel method administering tumstatin persistently. METHODS: The eukaryotic
      expression plasmid pcDNA-tumstatin encoding tumstatin gene was constructed and
      transfected to human umbilical vein endothelial cell ECV304 and human renal
      carcinoma cell ACHN. Expression of tumstatin in the two cell lines was determined
      by RT-PCR and Western blotting. Vascular endothelial cell proliferation was
      assessed by CCK-8 assay and cell cycle was analyzed by flow cytometry. To
      investigate the mechanism by which pcDNA-tumstatin inhibited vascular endothelial
      cell proliferation in vitro, cyclin D1 protein was detected by Western blotting.
      RESULTS: DNA sequence confirmed that pcDNA-tumstatin was successfully
      constructed. RT-PCR and Western blotting indicated that tumstatin could express
      in the two cell lines effectively. After tumstatin gene transfer, ECV304 cell
      growth was significantly inhibited and the cell cycle was arrested in G1 phase.
      And Western blotting showed that pcDNA-tumstatin decreased the level of cyclin D1
      protein. CONCLUSIONS: Overexpression of tumstatin mediated by pcDNA 3.1 (+)
      specially inhibited vascular endothelial cells by arresting vascular endothelial
      cell in G1 phase resulting from downregulation of cyclin D1 and administration of
      tumstatin using a gene therapy might be a novel strategy for cancer therapy.

PMID- 20819679
TI  - Clinical and genetic study of spinocerebellar ataxia type 7 in East Asian
      population.
AB  - BACKGROUND: Spinocerebellar ataxia type 7 (SCA7) is known as an autosomal
      dominant cerebellar ataxia; patients with genetically confirmed diagnoses of SCA7
      have increased rapidly in recent years. However, SCA7 is a rare subtype of SCA,
      and most data available about SCA7 are those of white people. The aim of the
      present study was to systematically review the prevalence and clinical and
      genetic aspects of SCA7 patients in East Asian population. METHODS: A search for
      publications on SCA7 was performed by using the "PubMed" database with the
      published language limited in English. Publications mainly focusing on the
      prevalence of SCA7 in patients with SCA and the clinical and genetic features of
      SCA7 patients were fully reviewed and analyzed. RESULTS: The prevalence of SCA7
      in SCA patients ranged from 0 to 7.7%, which was similar to those reported
      previously. The clinical manifestations were typically present at the 30's of its
      victims (median, 29 years; interquartile range (IQR), 19.5-36.5 years), and the
      symptoms appeared 15 years ((15.17+/-4.22) years) earlier on average in the
      offspring than in the parents. Gait ataxia and visual impairment were both found
      in all patients of whom the clinical features were described. Mutant SCA7 alleles
      contained 40-100 CAG repeats, with a median of 47 repeats (IQR, 44.5-50.0); and
      the offspring had 13 more repeats on average compared with their parents (12.62+/
      19.03). A strong negative correlation was found between CAG repeat size and the
      onset age of patients (r=-0.739, P=0.000). In addition, no significant difference
      was found in CAG repeat sizes between patients with visual impairment as the
      initial symptom and those with gait disturbance as their initial symptom
      (P=0.476). CONCLUSIONS: The prevalence of SCA7 in SCA patients, the age at onset
      and CAG repeats of SCA7 patients in East Asia are consistent with those of white
      people. However, larger population study is needed to assess the correlation
      between the CAG repeat size and initial symptoms of SCA7 patients in East Asia.

PMID- 20819680
TI  - Chylorrhea complicating D2+a gastrectomy: review of the literature and
      clarification of terminology apropos one case.

PMID- 20819681
TI  - Catheter ablation of paroxysmal atrial fibrillation in a young patient with a
      partial anomalous pulmonary venous connection.

PMID- 20819682
TI  - Expression analysis of ETS1 gene in peripheral blood mononuclear cells with
      systemic lupus erythematosus by real-time reverse transcription PCR.

PMID- 20819694
TI  - [Serotonin: a player in both depression and bone remodeling].

PMID- 20819695
TI  - [Function of NMDA receptors activated by astrocytic glutamate on postnatal
      neurogenesis].

PMID- 20819696
TI  - [mGluR5: a receptor at the therapeutic crossroad?].

PMID- 20819697
TI  - [Elastase 2, a key player in the integrity of the epidermal barrier and in
      Netherton syndrome].

PMID- 20819698
TI  - [The complex relations between haemoglobinopathies and malaria].

PMID- 20819699
TI  - [Human asthenozoospermia and structural defects of the annulus].

PMID- 20819700
TI  - [Normal spermatogenesis in a patient with mutant luteinizing hormone].

PMID- 20819701
TI  - [Blood vessel growth by matrix contraction].

PMID- 20819702
TI  - [Unravelling the mysteries of biased DNA segregation during mitosis].

PMID- 20819703
TI  - [Tbx5 and the heart adaptation to life on earth].

PMID- 20819704
TI  - [Genetic and breeding of Artemisia annua L. for a sustainable production of the
      antimalarial drug artemisinin].

PMID- 20819705
TI  - [Nedd4/PTEN in axonal branching].

PMID- 20819707
TI  - [Serotonin, two faces of a unique molecule in the regulation of bone mass].
AB  - During the last 20 years, the emergence of sophisticated genetic tools has
      extraordinarily improved our understanding of a large number of physiological
      functions, among which the physiology of the skeleton. Bone, recently described
      as an endocrine organ, has the ability to constantly renew itself through bone
      remodeling, which requires a constant supply of energy. Hence, we hypothesized
      that there must be a coregulation of bone mass and energy metabolism, and focused
      on leptin, an adipocyte-derived hormone, which regulates both energy metabolism
      and bone remodeling through a central relay. Through a careful analysis of leptin
      neuronal targets, we unraveled that leptin regulation of bone mass occurs
      indirectly by inhibiting serotonin release and synthesis in neurons of the
      brainstem. Surprisingly, we observed that the other pool of serotonin, produced
      in enterochromaffin cells of the duodenum, negatively regulates bone mass
      accrual. Thus, serotonin is a molecule with two distinct functional identities
      depending on its site of synthesis. Finally, a recent study provides a proof of
      principle that inhibiting gut-derived serotonin (GDS) biosynthesis could become a
      new anabolic treatment for osteoporosis. double dagger.

PMID- 20819708
TI  - [Drugs as risk factors of food anaphylaxis in adults].
AB  - Anaphylaxis is the most severe type of food allergy. Factors of risk are advanced
      age, cardiopathy, asthma, mastocytosis. Age may be linked to an increased
      consumption of drugs: aspirin, nonsteroidal anti-inflammatory drugs, beta
      blockers, inhibitors of angiotensin converting enzyme (ACE). A case-control study
      comparing anaphylaxis and mild food allergies has shown a sharp increase of
      consumption of these drugs in patients with anaphylaxis, with odds ratio
      respectively of 10.8 [CI 95%: 3.10-41.3], 8.2 [CI 95%: 1.37-62.51], 6.8 [CI 95%:
      1.78-27.78] and 13 [CI 95%: 1.34-310.38]. Besides, exercise potentiates the
      relative risk of drug consumption. Predominant mechanisms could be an increase of
      gut permeability enhancing the passage of food allergens in the mucosa and in
      blood, and the inhibition of ACE, so that the angiotensin homeostatic mechanism
      deteriorates. Main sites of interference may be endothelium and gut epithelium.
      Preventive measures excluding the intake of aspirin and nonsteroidal anti
      inflammatory drugs before the meals can be recommended for food allergic and food
      sensitized adults. Treatment of hypertension can address to other families of
      drugs than ACE inhibitors (ACEI) and beta blockers. The benefit-risk ratio of
      beta blockers and ACEI has to be carefully considered in the case of cardiopathy.
      double dagger.

PMID- 20819709
TI  - [Marked for life: synaptic stabilisation leaves an indelible trace on neuronal
      partners: a question of etiquette for neurons?].
AB  - Recent in vivo and in vitro studies have used the rodent olivocerebellar path to
      examine developmental synaptogenesis, in particular the mechanisms which permit
      the simultaneous stabilisation of some synapses and elimination of others. They
      reveal that while the formation of synapses can take place throughout life,
      elimination of supernumerary connections is limited to a critical period during
      development. Synapse elimination involves the strengthening of appropriate
      synapses and weakening of others, which are subsequently removed. This process is
      partly dependent on activity and post-synaptic signalling cascades and
      irreversibly changes each synaptic partner, leaving a trace of previous
      connectivity. Here we discuss the nature of this << trace >>, which may be a
      molecule that labels and protects those synapses to be retained, and its
      functional significance in maintaining the specificity of neuronal circuits
      needed for coordinate behaviour. double dagger.

PMID- 20819710
TI  - [Regulation of cell survival by RAF kinases].
AB  - The RAF proteins (A-RAF, B-RAF et C-RAF) are a family of kinases that play a key
      role in the regulation of various aspects of cell physiology, among which cell
      proliferation, differentiation and survival. We review the literature regarding
      their anti-apoptotic effects, and we summarize the current view regarding how
      alterations in these mechanisms contribute to human carcinogenesis. Finally, we
      discuss new therapeutic perspectives based on the manipulation of cell survival
      by the RAF kinase pathway. double dagger.

PMID- 20819711
TI  - [Functional selectivity of opioid receptors ligands].
AB  - Opiates are the most effective analgesics available for the treatment of severe
      pain. However, their clinical use is restricted by unwanted side effects such as
      tolerance, physical dependence and respiratory depression. The strategy to
      develop new opiates with reduced side effects has mainly focused on the study and
      production of ligands that specifically bind to different opiate receptors
      subtypes. However, this strategy has not allowed the production of novel
      therapeutic ligands with a better side effects profile. Thus, other research
      strategies need to be explored. One which is receiving increasing attention is
      the possibility of exploiting ligand ability to stabilize different receptor
      conformations with distinct signalling profiles. This newly described property,
      termed functional selectivity, provides a potential means of directing the
      stimulus generated by an activated receptor towards a specific cellular response.
      Here we summarize evidence supporting the existence of ligand-specific active
      conformations for two opioid receptors subtypes (delta and mu), and analyze how
      functional selectivity may contribute in the production of longer lasting, better
      tolerated opiate analgesics. double dagger.

PMID- 20819712
TI  - [Radiotherapy and atherosclerosis: current data and issues].
AB  - The continuous optimization of cancer treatment with radiotherapy raises the
      problem of long-term issue of patients treated and cured by ionizing radiation,
      with the possible occurrence of second cancers or nonmalignant complications.
      Among these, cardiovascular diseases are prevalent and may affect up to 40 % of
      patients depending on the location of the irradiation. Recent epidemiological
      studies show that this problem is underestimated and with no real prospective
      studies. The management of these patients with vascular risk, or with very high
      vascular risk for those with pre-existing traditional cardiovascular risk
      factors, remains to be determined. The pathophysiological mechanisms of radiation
      induced atherosclerosis have not yet been clarified. Many efforts are still
      needed to identify patients at risk and to find or to propose an appropriate
      treatment. Prolonged vascular follow-up of patients after their radiotherapy
      should now be integrated into patterns of care, especially because the setting up
      of sophisticated technical platforms of radiotherapy do not necessarily solve the
      issue of cardiovascular risk after treatment. double dagger.

PMID- 20819713
TI  - [Positive interaction between immunosuppressive and antifungal drugs].
AB  - Immunosuppressive and antifungal drugs are frequently associated to treat solid
      organ transplant patients or patients with hematological malignancies. To cure
      invasive fungal infection (IFI), immunosuppression has to be reduced. However,
      immunosuppressive drugs such as cyclosporin A, tacrolimus, sirolimus (rapamycin)
      or mycophenolate mofetil possess antifungal properties. Indeed fungi and humans
      have in common calcineurin and TOR signalization pathways which are inhibited by
      these molecules. In vitro experiences suggest a positive interaction between
      immunosuppressive and antifungal drugs such as amphotericin B, azole and
      echinocandins. These results are confirmed by clinical findings and thus offer
      further therapeutic possibilities in the context of solid organ transplantation.
      double dagger.

PMID- 20819714
TI  - [O-GlcNAc glycosylation and regulation of cell signaling].
AB  - O-GlcNAcylation corresponds to the addition of N-acetylglucosamine on serine and
      threonine residues of cytosolic and nuclear proteins. O-GlcNAcylation is a
      dynamic post-translational modification, analogous to phosphorylation, that
      regulates the stability, the activity or the sub-cellular localisation of
      proteins. This reversible modification depends on the availability of glucose and
      therefore constitutes a powerful means by which cellular activities are regulated
      according to the nutritional environment of the cell. O-GlcNAcylation has been
      implicated in important human pathologies including Alzheimer disease and type-2
      diabetes. Only two enzymes, OGT and O-GlcNAcase, control the O-GlcNAcylation
      level on proteins, and thereby regulate signaling pathways. Several lines of
      evidence indicate that OGT attenuates insulin signal by O-GlcNAcylation of
      proteins involved in proximal and distal steps in the signaling pathway. This
      negative feedback may be exacerbated when cells are exposed to elevated glucose
      concentrations as observed in diabetic patients, and could thereby contribute to
      insulin resistance and worsening of hyperglycaemia. double dagger.

PMID- 20819715
TI  - [Hybrid nanocarriers for controlled delivery of antitumour and retroviral drugs
      delivery].
AB  - The efficient delivery of drugs in the body requires the use of non-toxic
      nanocarriers. Most of the existing materials show poor drug loading and/or rapid
      release of the proportion of the drug that is simply adsorbed (or anchored) at
      the external surface of the nanocarrier. The new porous hybrid solids, with the
      ability to tune their structures and porosities are well suited to serve as
      nanocarriers for delivery and imaging applications. Here we show that specific
      non-toxic porous iron(III) - based metal - organic frameworks with engineered
      cores and surfaces, as well as imaging properties, function as superior
      nanocarriers for efficient controlled delivery of antitumour and retroviral drugs
      against cancer and AIDS. They also potentially associate therapeutics and
      diagnostics, and open the way for theranostics, or -personalized patient
      treatments. double dagger.

PMID- 20819716
TI  - [The history of the clinical research settlement in French hospitals].
AB  - Since 1992, French clinical research centers (CRC) allow physicians and
      researchers to develop clinical and therapeutic research on humans in public
      hospitals. Created by the National institute for health and medical research
      (Inserm) in collaboration with public hospitals, their history give us the
      opportunity to describe the complex interactions in France between fundamental
      and clinical research. Why does therapeutic research need CRC? What can be done
      in these structures that cannot be done in hospital wards? Medical research is an
      hybrid practice torn between fundamental and clinical methodologies and
      objectives. To solve this tension, CRC are << trading zones >> (Galison, 1997):
      intermediate areas where physicians and researchers can develop -common languages
      and methodologies to coordinate their practices and objectives. CRC also become
      essential to support the ethical, legal and administrative constraints of
      therapeutic research. double dagger.

PMID- 20819717
TI  - [Fetuses born lifeless: new representations and new rights].
AB  - A february-2008 rule about << children born lifeless >> stressed that << every
      fetus born lifeless >> could be registered at the General Register Office. This
      rule, which was followed in 2009 by the implementation of new procedures to deal
      with dead fetuses, highlighted that this topic is more and more becoming an
      important public issue. The rights for parents to choose has now been recognized,
      bringing about new questions for health professionals. Another point is which
      symbolism is to be given to dead fetuses to alleviate couples' suffering, without
      being too ideological, i.e. seeing fetuses as persons. This change also makes
      professionals reconsider public health system priorities, and this at a very
      particular time. Indeed, as parent mourning has now been made easier through
      registration at the General Register Office, there has not been any rule yet
      linking national epidemiological registration and fetal death in France. double
      dagger.

PMID- 20819721
TI  - Application of bioluminescence imaging to therapeutic intervention of herpes
      simplex virus type I - Thymidine kinase/ganciclovir in glioma.
AB  - Lentiviral vector containing the HSV1-tk and firefly luciferase (fLuc) gene was
      infected into C6 and C6-TL expressing HSV1-tk and fLuc gene was generated. C6-TL
      showed higher [(125)I]IVDU uptake than C6. The survival rate of C6-TL decreased
      more rapidly with increasing GCV dose and was well correlated with fLuc activity.
      The images of microPET clearly demonstrated higher uptake of [(18)F]FHBG into the
      C6-TL tumor. Inhibition of tumor growth was observed in C6-TL tumor-bearing mice
      treated with GCV through tumor size measurement and bioluminescence imaging. The
      therapeutic effect of HSV1-tk/GCV system can be monitored using bioluminescent
      imaging and tumor size measurement.

PMID- 20819722
TI  - Determination of selenium content in aqueous extract of medicinal plants used as
      herbal supplement for cancer patients.
AB  - The chemical constituents in medicinal plants (MPs), including elements, are
      partially responsible for their medicinal and nutritional properties as well as
      toxic effects. This research aimed to monitor selenium (Se) contents in aqueous
      extract of MPs used for treatment of cancer and different diseases. In present
      work the Se in MPs was extracted in aqueous media by microwave-assisted (ME) and
      conventional extraction (CE) methods. The total and residual Se in MPs were
      determined, prior to microwave-assisted acid digestion. The Se in aqueous
      extracts and digests were analysed by electrothermal atomic absorption
      spectrometry. The optimum extractable Se in MPs were obtained by ME and CE,
      required 2 and 40 min, respectively. Precision and accuracy of the methodologies
      were checked by standard addition method. The Se contents in aqueous extract of
      MPs were found in the range of 1.09-2.23 MUg/g corresponding to 21-33% of total
      Se contents. The daily intake of Se from aqueous extract of MPs as recommended by
      herbalist (10 g of plant material) was found in the range of 20-40% of daily
      requirement.

PMID- 20819748
TI  - [Pulmonary hypertension: great expectations].

PMID- 20819749
TI  - [Prostanoids in the treatment of pulmonary arterial hypertension].
AB  - Prostacyclin, endothelin-1, and nitric oxide pathways are involved in the
      pathogenesis of pulmonary arterial hypertension. This devastating disease of the
      pulmonary vasculature is associated with vasoconstriction, thrombosis and
      proliferation, and this may be partly due to lack of endogenous prostacyclin
      secondary to prostacyclin synthase downregulation. Prostanoids (prostacycin
      analogues) are potent vasodilators and possess antiaggregant, antiinflammatory
      and antiproliferative properties. The first agent to be approved for the
      treatment of pulmonary arterial hypertension was epoprostenol. In the last decade
      other prostanoids (treprostinil, iloprost) has been approved for the treatment of
      pulmonary arterial hypertension.

PMID- 20819750
TI  - [Endothelin receptor antagonists in pulmonary arterial hypertension].
AB  - Endothelin-1 (ET-1) is the most potent vasoconstrictor agent resulting in
      increased pulmonary vascular resistance and has proliferative effects on the
      vascular smooth muscle cells. Evidence for the relationship between increased
      blood levels of ET-1 and disease severity in pulmonary arterial hypertension
      (PAH) established the basis of specific approach targeted to endothelin pathway
      in PAH. The results of the observational studies and randomized controlled trials
      revealed that endothelin receptor antagonists (ERAs) compared with conventional
      medication may improve exercise tolerance and functional status, quality of life,
      right ventricular function and pulmonary hemodynamics and may lengthen the time
      to clinical worsening and survival in patients with PAH. Recently, the
      indications for ERAs in PAH seem to expand from class III and IV to class II
      symptomatology. In this review, we aimed to outline therapeutic benefits, drug-to
      drug interactions and safety profile of different ERAs as specific agents of
      monotherapy or as a component of combination therapy in patients with PAH from
      the perspective of the evidence-based medicine.

PMID- 20819751
TI  - [Phosphodiesterase type 5 inhibitors in the treatment of pulmonary arterial
      hypertension].
AB  - The pathology of pulmonary arterial hypertension (PAH) is characterized by
      vascular vasoconstriction, smooth muscle cell proliferation, and thrombosis.
      Experimental studies have shown the beneficial effect of phosphodiesterase type 5
      (PDE-5) inhibitors on pulmonary vascular remodeling and vasodilatation.
      Randomized clinical trials in monotherapy or combination therapy have been
      conducted in PAH with sildenafil and tadalafil which significantly improve
      clinical status, exercise capacity and hemodynamics of PAH patients. Combination
      therapy of PDE-5 inhibitors with prostacyclin analogs and endothelin receptor
      antagonists may be helpful in management of PAH. The third PDE-5 inhibitor,
      vardenafil, is currently being investigated in PAH. Side effects are usually mild
      and transient and include headache, flushing, nasal congestion, digestive
      disorders, and myalgia.

PMID- 20819752
TI  - [Therapeutic algorithms in pulmonary hypertension in the light of current
      guidelines].
AB  - Pulmonary arterial hypertension (PAH) is a clinical syndrome that is often
      diagnosed late and is associated with a progressive clinical deterioration and
      death. However, over the past ten years there has been a dramatic increase in the
      number of effective therapies. Identification of dysfunctional pathways in the
      pulmonary circulation provided novel therapeutic targets with the goal of
      reducing pulmonary vascular resistance and death from right ventricular failure.
      Treatment strategies are determined according to current guidelines. Pulmonary
      artery vasoreactivity, functional class and response to treatment are important
      concepts for initiation of medical therapy. With the availability of medications
      that target different pathologic processes, combination therapy has become a
      frequently used therapeutic option in PAH. In this paper, we aimed to review the
      therapeutic algorithms in pulmonary hypertension based on current guidelines.

PMID- 20819753
TI  - [Atrial septostomy in pulmonary hypertension].
AB  - Despite the fact that remarkable improvements have been achieved in quality of
      life and survival through increasing number of specific medical treatment
      alternatives in severe pulmonary hypertension, many patients have resistance to
      medical treatment. Atrial septostomy is considered as a palliative procedure in
      severe pulmonary hypertension to relieve symptoms of severe pulmonary
      hypertension by reducing right ventricular preload and increasing systemic flow.
      Gradual balloon dilatation and blade balloon atrial septostomy are the most
      frequently used methods. If atrial septostomy is performed in experienced medical
      centers, it provides clinical improvement and even has tendency to extend life
      expectancy in patients with pulmonary hypertension resistant to medical
      treatment.

PMID- 20819754
TI  - [Pulmonary thromboendarterectomy].
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease
      characterized by the persistence of thromboemboli obstructing the pulmonary
      arteries as an organized tissue. The consequence is an increase in pulmonary
      vascular resistance resulting in pulmonary hypertension (PH) and progressive
      right heart failure. Pulmonary thromboendarterectomy (PTE) is the treatment of
      choice of chronic thromboembolic pulmonary disease. Pulmonary
      thromboendarterectomy is performed under hypothermia and total circulatory
      arrest. This procedure is associated with a low mortality rate in experienced
      centers and results in a dramatic improvement of hemodynamic parameters,
      functional status and survival rate. This surgery should be performed as early as
      possible in the history of this disease, preferentially before development of
      arteriolitis in the non obstructed territories. Because of the absence of
      clinically evident acute pulmonary embolism history in >50% of patients, the
      diagnosis of CTEPH can be difficult. Lung scintigraphic scan showing segmentary
      mismatched perfusion defects is the best diagnostic tool to detect CTEPH.
      Pulmonary angiography and high-resolution computerized tomography scan are
      required to establish the diagnosis and to assess the operability. A diagnostic
      right heart catheterization is required to confirm the diagnosis of PH and to
      determine the degree of hemodynamic impairment. If there is a good correlation
      between the pulmonary vascular resistance and the anatomical obstruction,
      pulmonary thromboendarterectomy should be proposed. Pulmonary or cardiopulmonary
      transplantation is indicated in this setting only when the lesions are too distal
      and thus inaccessible to endarterectomy.

PMID- 20819755
TI  - [Transplantation in pulmonary hypertension].
AB  - Pulmonary hypertension is one of the indications for lung transplantation. Recent
      advances on medical management of the disease have dramatically decreased the
      number of patients who required lung transplantation. In reported series, single
      or double lung transplantation have been successfully undertaken by many
      transplant centers. In patients, whose cardiac functions are irreversibly damaged
      heart-lung transplantation remains as an only option for long term survival.
      Transplantation should only be considered in those patients who are having
      optimal medical support and relatively good condition for a major operation.

PMID- 20819756
TI  - [Pulmonary hypertension caused by left heart disease].
AB  - Increased resistance to pulmonary venous drainage is the main mechanism in
      pulmonary hypertension (PH) developing due to left heart disease. This condition
      may occur as a result of various diseases affecting left ventricle, left atrium,
      mitral or aortic valves. Pulmonary hypertension is the common and well-recognized
      complication of left ventricular systolic dysfunction and pulmonary arterial
      hypertension accompanying chronic heart failure is related to increased
      mortality. Treatment should be tailored according to the underlying disease.

PMID- 20819757
TI  - [Pulmonary hypertension related to pulmonary diseases or hypoxia and its
      treatment].
AB  - Pulmonary hypertension often complicates the course of patients with advanced
      lung disease, and it is associated with a worse prognosis. In the recent
      classification of pulmonary hypertensive disorders, pulmonary hypertension due to
      lung disease is considered as a separate category within a group of disorders
      that were previously referred to as "secondary". The incidence and clinical
      course of pulmonary hypertension associated with chronic obstructive pulmonary
      disease is best known among the pulmonary hypertension associated with lung
      diseases. The pathophysiology and treatment of pulmonary hypertension seen in the
      course of advanced lung diseases are generally distinct from those of pulmonary
      arterial hypertension. Chronic hypoxia is the major mechanism implicated for the
      development of pulmonary hypertension in patients with lung diseases. This
      article focuses on the recent advances in our knowledge about the pulmonary
      hypertension due to lung diseases or hypoxia.

PMID- 20819758
TI  - [Chronic thromboembolic pulmonary hypertension: diagnosis, medical therapy and
      monitoring].
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by obstruction of
      the large pulmonary arteries by acute and recurrent pulmonary emboli with
      subsequent organization of these blood clots. Because of a lack of clinically
      evident acute-pulmonary embolism episodes in >50% of patients, the diagnosis of
      CTEPH can be difficult. Lung ventilation/perfusion scintigraphy showing
      segmentary mismatched perfusion defects is the best diagnostic tool to detect
      CTEPH. Although pulmonary endarterectomy is considered the treatment of choice
      for patients with CTEPH, it can not be performed in a substantial proportion of
      patients. Medical therapies have been increasingly used in subcategories of CTEPH
      patients.

PMID- 20819759
TI  - [The odyssey of pulmonary hypertension].

PMID- 20819760
TI  - [Pulmonary hypertension: diagnosis and clinical classification].
AB  - Pulmonary hypertension (PH) is a complex disease with limiting the physical
      activity, life expectancy significantly and requires multidisciplinary approach.
      In recent years, a dramatic increase was observed in the understanding and
      management of the disease. The first clinical classification of PH was made in
      Evian (France) in 1973 and the last clinical classification of PH was made in
      Dana Point (USA) in 2008. Diagnosis and clinical classification of PH is
      discussed in this review.

PMID- 20819761
TI  - [The etiopathogenesis of pulmonary hypertension: inflammation, vascular
      remodeling].
AB  - Pulmonary arterial hypertension (PAH) is a progressive disease marked by
      increased pulmonary artery resistance leading to right heart failure with a high
      mortality. PAH is histologically characterized by endothelial and smooth muscle
      cell proliferation, medial hypertrophy, inflammation, and thrombosis in situ.
      Elevated pulmonary vascular resistance is the result of an imbalance between
      locally produced vasodilators and vasoconstrictors, in addition to vascular wall
      remodeling. Recent evidence demonstrates that inflammatory processes are involved
      in the generation of pulmonary vascular remodeling leading to PAH. Viral
      infections or similar immune-modulators trigger auto-antibody generation by
      endothelial injury and indirectly lead to PAH. All these immune-modulators
      associated with PAH, are also known to decrease the regulatory subgroups (CD4) of
      T cells. With a recognition of the important role of inflammation in the
      development of PAH, anti-inflammatory agents and anti-cancer drugs are accepted
      as potential specific targets for PAH treatment. Though clinical studies are not
      enough, anti-inflammatory agents seem to be promising in the treatment of this
      devastating disease.

PMID- 20819762
TI  - [Genetic, cellular and molecular mechanisms of pulmonary arterial hypertension].
AB  - Pulmonary arterial hypertension (PAH) is an uncommon disorder that may be
      hereditable, idiopathic or associated with conditions like drug exposure,
      connective tissue disease, HIV infection or congenital heart disease. Familial
      disease are usually due to mutations in the bone morphogenic protein receptor
      type 2 (BMPR2), activin-like kinase-type 1 (ALK1) and endoglin (ENG). Functional
      and structural changes in the pulmonary vasculature lead to increased pulmonary
      vascular resistance. Vascular remodeling involves endothelial dysfunction,
      activation of fibroblasts and smooth muscle cells and recruitment of circulating
      progenitor cells. Vasoconstriction has also been shown to affect the remodeling
      process. Genetics, cellular and molecular basis of PAH are discussed in the
      paper.

PMID- 20819763
TI  - [Diagnostic algorithms in pulmonary hypertension].
AB  - Pulmonary hypertension is a serious disease with a poor prognosis. The diagnosis
      and assessment of pulmonary hypertension is evolving rapidly with changes in the
      definition of the disease, diagnostic techniques and follow-up assessment.
      Different conditions associated with pulmonary hypertension and new diagnostic
      techniques have led to a need for a systematic diagnostic approach. This review
      article presents an update on alterations in the diagnostic algorithm.

PMID- 20819764
TI  - [Echocardiography and other imaging modalities in pulmonary arterial
      hypertension].
AB  - It is essential to diagnose pulmonary arterial hypertension in early stages of
      the disease. However, most patients have late diagnosis due to the lack of
      disease-specific symptoms and prominent findings. Although cardiac
      catheterization is the gold standard in the diagnosis of pulmonary arterial
      hypertension, noninvasive diagnostic modalities do also have major roles in the
      diagnosis, risk assessment and follow-up of the patients with pulmonary arterial
      hypertension. The focus of the present review is the clinical role of
      echocardiography and other imaging modalities in pulmonary arterial hypertension.

PMID- 20819765
TI  - [Clinical end-points and surrogate markers of pulmonary arterial hypertension in
      the light of evidence-based treatment].
AB  - Pulmonary arterial hypertension (PAH) is a rare, fatal and progressive disease.
      There is an acceleration in the advent of new therapies in parallel to the
      development of the knowledge about etiogenesis and pathogenesis of PAH.
      Therefore, to optimize the goals of PAH-specific treatment and to determine the
      time to shift from monotherapy to combination therapy, simple, objective and
      reproducible end-points, which may predict the disease severity, progression rate
      and life expectancy are needed. The adventure of end points in PAH has started
      with six minute walk distance and functional capacity, and continues with new
      parameters (biochemical marker, time to clinical worsening, echocardiography and
      magnetic resonance imaging etc.), which can better reflect the clinical outcome.

PMID- 20819766
TI  - [Pulmonary vasoreactivity testing in diagnosis and prognosis of pulmonary
      hypertension].
AB  - Right heart catheterization (RHC) is required for confirmation of the diagnosis
      of pulmonary hypertension (PH) and to asses the prognosis and etiology. Pulmonary
      vasoreactivity testing (PVT) is one of the most crucial parts of RHC especially
      in the suitable patient subsets of pulmonary arterial hypertension (PAH) defined
      by the most recent guidelines. PVT has substantial importance in defining the
      most appropriate treatment modality. The aim of this review is to provide a
      comprehensive review of the literature about PVT and the agents used in PVT, to
      emphasize the importance of this procedure when done with correct indications
      with a correct technique and to contribute in the accurate management of PH
      patients.

PMID- 20819767
TI  - [Pediatric pulmonary hypertension and pulmonary arterial hypertension secondary
      to congenital heart diseases].
AB  - Causes of pulmonary arterial hypertension (PAH) are similar in adults and
      children. The main difference is that PAH secondary to congenital heart diseases,
      is the predominant cause in pediatric patients. Persistent pulmonary hypertension
      of the newborn shows completely different clinical course and pathophysiological
      mechanisms. It is usually seen in full term babies with a high morbidity and
      mortality rate. Improved prognosis has been reported with inhaled nitric oxide
      (NO) and extracorporeal membrane oxygenation therapy in babies hospitalized in
      well equipped and experienced newborn centers. Primary pulmonary hypertension and
      familial pulmonary hypertension are rare in pediatric age group because the
      diagnosis is initially made in adolescence. The incidence of PAH secondary to
      congenital heart disease is estimated as 1.6 - 12.5 case/million/year.
      Eisenmenger syndrome is diagnosed in 1% of patients with PAH. Patients with left
      to right shunts are the main group who develop pulmonary vascular disease if not
      treated in the early infancy. Some cyanotic congenital heart diseases are also
      the causes of PAH. The best treatment of patients at risk for the development of
      pulmonary vascular disease is prevention by early surgical elimination of defects
      or repairing the anatomy. Treatment options with vasodilating agents like NO,
      prostaglandin analogs, phosphodiesterase -5 inhibitors and endothelin receptor
      antagonists are used to improve survival and quality of life. Heart lung or
      bilateral lung transplantation is the only surgical option for many of these
      patients. Results of national and international registries will bring valuable
      epidemiological and prognostic perspectives to pediatric PAH.

PMID- 20819768
TI  - [Pulmonary arterial hypertension related to connective tissue diseases].
AB  - Pulmonary arterial hypertension (PAH) is an important complication of connective
      tissue diseases (CTD) and especially seen in systemic sclerosis, systemic lupus
      erythematosis (SLE), and mixed connective tissue disease (MCTD). In systemic
      sclerosis, PAH is isolated or accompanied by interstitial lung disease and
      currently, a major cause of mortality. It has been shown to be developed in
      approximately 10% of cases and annual screening with echocardiography has been
      recommended. Right heart catheterization is required for definite diagnosis.
      Limited skin involvement, late onset, Raynaud's phenomenon, digital ulcers,
      telangiectasias, diminished nail fold capillaries, anti-U3RNP and anticentromere
      antibodies are known as risk factors for PAH development in systemic sclerosis.
      Following diffusion lung capacity for carbon monoxide (DLCO) and pro-brain
      natriuretic peptide (pro-BNP) levels can be helpful for evaluating PAH
      development. PAH in SLE linked to antiphospholipid antibodies and Raynaud's
      phenomenon in some studies. MCTD is an overlap syndrome with features of systemic
      sclerosis, SLE, polymyositis and positive anti-U1RNP antibodies. PAH develops in
      9-27% of the patients and the leading cause of mortality in patients with MCTD.
      Endothelin receptor antagonists, prostacyclin analogs and phosphodiesterase 5
      inhibitors are being used in patients with systemic sclerosis. In SLE/MCTD
      patients with early diagnosis immunosuppressive treatments may be effective.

PMID- 20819769
TI  - [Other causes of pulmonary arterial hypertension: pulmonary veno-occlusive
      disease, pulmonary capillary hemangiomatosis, porto-pulmonary hypertension, HIV-
      associated pulmonary arterial hypertension].
AB  - Idiopathic pulmonary arterial hypertension (PAH) is included in Group 1 of PAH
      classification, while pulmonary veno-occlusive disease (PVOD), pulmonary
      capillary hemangiomatosis (PCH), portopulmonary hypertension (PoPH) and HIV
      associated PAH constitute the subgroups of Group I PAH disorders. PVOD has
      similar clinical presentation, hemodynamic characteristics and genetic background
      with PAH although main pathology is in venules and definite diagnosis is done by
      biopsy although not recommended due to high risk of bleeding. PCH, a rare
      idiopathic lung disorder, causes PAH in young adults and mostly is diagnosed
      after death by autopsy. PoPH is defined as PAH due to primary chronic liver
      disease associated with intrapulmonary vascular dilatations and hypoxia. HIV
      associated PAH is a rare complication of HIV-infection, and it is seen especially
      in HIV-infected patients with intravenous drug abuse.

PMID- 20819770
TI  - Reinke's edema: investigations on the role of MIB-1 and hepatocyte growth factor.
AB  - Reinke's edema is a benign disease of the human vocal fold, which mainly affects
      the sub-epithelial layer of the vocal fold. Microscopic observations show a
      strongly oedematous epithelium with loosened intercellular junctions, a
      disruption of the extracellular connections between mucosal epithelium and
      connective tissue, closely adherent to the thyroarytenoid muscle. Thickening of
      the basal layer of epithelium, known as Reinke's space, high deposition of
      fibronectin and chronic inflammatory infiltration it is also visible. We
      analyzed, together with the hepatocyte growth factor (HGF), the expression level
      of MIB-1 in samples harvested from patients affected by Reinke's edema, in order
      to define its biological role and consider it as a possible prognostic factor in
      the follow-up after surgical treatment. We observed a moderate expression of HGF
      in the lamina propria of the human vocal fold and in the basal membrane of the
      mucosal epithelium. Our finding suggests that this growth factor acts as an
      antifibrotic agent in Reinke's space and affects the fibronectin deposition in
      the lamina propria. MIB-1, on the contrary, showed a weak expression in the
      basement membrane of the mucosal epithelium and a total absence in the lamina
      propria deep layer, thus suggesting that only the superficial layer is actively
      involved in the reparatory process with a high regenerative capacity, together
      with a high deposition of fibronectin. The latter is necessary for the cellular
      connections reconstruction, after the inflammatory infiltration.

PMID- 20819771
TI  - Routinely frozen biopsies of human skeletal muscle are suitable for morphological
      and immunocytochemical analyses at transmission electron microscopy.
AB  - The aim of the present investigation was to evaluate whether routinely frozen
      biopsies of human skeletal muscle may be suitable for morphological and
      immunocytochemical analyses at transmission electron microscopy. The
      fixation/embedding protocols we successfully used for decades to process fresh
      mammalian tissues have been applied to frozen muscle biopsies stored for one to
      four years in liquid nitrogen. After 2.5% glutaraldehyde - 2% paraformaldehyde -
      1% OsO4 fixation and embedding in epoxy resin, the ultrastructural morphology of
      myofibres and satellite cells as well as of their organelles and inclusions
      proved to be well preserved. As expected, after 4% paraformaldehyde - 0.5%
      glutaraldehyde fixation and embedding in LR White resin, the morphology of
      membrane-bounded organelles was relatively poor, although myofibrillar and
      sarcomeric organization was still recognizable. On the contrary, the myonuclei
      were excellently preserved and, after conventional staining with uranyl acetate,
      showed an EDTA-like effect, i.e. the bleaching of condensed chromatin, which
      allows the visualization of RNP-containing structures. These samples proved to be
      suitable for immunocytochemical analyses of both cytoskeletal and nuclear
      components, whereas the poor mitochondrial preservation makes unreliable any in
      situ investigation on these organelles. Keeping in mind the limitations found,
      these results open promising perspectives in the study of frozen skeletal muscle
      samples stored in the tissue banks; this would be especially interesting for rare
      muscle diseases, where the limited number of biopsies suitable for
      ultrastructural investigation has so far represented a great restriction in
      elucidating the cellular mechanisms responsible for the pathological phenotype.

PMID- 20819772
TI  - Detecting microcalcifications in atherosclerotic plaques by a simple trichromic
      staining method for epoxy embedded carotid endarterectomies.
AB  - Atherosclerotic plaques have a high probability of undergoing rapid progression
      to stenosis, becoming responsible of acute coronary syndrome or stroke.
      Microcalcifications may act as enhancers of atherosclerotic plaque vulnerability.
      Considering that calcifications with a diameter smaller than 10 mm in paraffin
      embedded tissue are rather difficult to detect, our aim was to analyze
      microcalcifications on semithin sections from epoxy resin embedded samples of
      carotid endarterectomies using an original trichromic stain (methylene blue--azur
      B--basic fuchsine--alizarin red). We have compared samples stained either with
      our method, methylene blue-azur B alone or with Von Kossa staining, and methylene
      blue-azur B -basic fuchsine alone or with Von Kossa staining. Our method resulted
      to be simple and fast (ca. 2 min), it gives a sharp general contrast for all
      structures and allows to easy identify collagen and elastin. In addition, gray
      green colour associated to intracellular lipid droplets evidences foam cells,
      which are particularly abundant in endarterectomies samples. Mast cells and their
      metachromatic granules are also well recognized. Calcifications over 0,5 mm are
      clearly recognizable. In conclusion, microcalcifications are clearly
      distinguished from the extracellular matrix in spite of their reduced dimensions.
      Methylene blue--azur B--basic fuchsine--alizarin red method is easy to use,
      reproducible, and is particularly suitable for the identification of
      microcalcifications in the morphological analysis of atherosclerotic plaques.

PMID- 20819773
TI  - Expression of lumican in the articular disc of the human temporomandibular joint.
AB  - Lumican belongs to the small leucine-rich repeat proteoglycan (SLRP) gene family
      and has been reported to exist in the cornea, intervertebral disc and tendon.
      Lumican plays a significant role in the assembly and regulation of collagen
      fibres. The human temporomandibular joint (TMJ) disc is made up of fibrocartilage
      with an extracellular matrix (ECM) composed of collagen and proteoglycans. The
      existence and behaviour of lumican has not been studied in the human TMJ disc.
      Therefore, we used immunohistochemical methods to detect lumican, CD34 and
      vascular endothelial growth factor (VEGF) and histochemical staining with
      toluidine blue in 13 human TMJ specimens (10 surgically removed and 3 obtained
      from autopsy). In both the normal and the deformed discs we observed staining
      with toluidine blue. We found that the area of metachromasia inside the deformed
      disc was uneven and expression of lumican was strong in the areas negative for
      metachromasia. Staining of VEGF and CD34 inside the deformed disc was seen. We
      confirmed the expression of lumican in the human TMJ disc and showed that a large
      number of fibroblast-like cells existed in the area of strong lumican expression.
      These new findings about the behaviour of lumican suggest that it may play a key
      role in the generation of a new collagen network by fibroblast-like cells.

PMID- 20819774
TI  - Histochemical and morpho-metrical study of mouse intestine epithelium after a
      long term diet containing genetically modified soybean.
AB  - Diet can influence the structural characteristics of both small and large
      intestine. In this study, we investigated the duodenum and colon of mice fed on
      genetically modified (GM) soybean during their whole life span (1-24 months) by
      focusing our attention on the histological and ultrastructural characteristics of
      the epithelium, the histochemical pattern of goblet cell mucins, and the growth
      profile of the coliform population. Our results demonstrate that controls and GM
      soybean fed mice are similarly affected by ageing. Moreover, the GM soybean
      containing diet does not induce structural alterations in duodenal and colonic
      epithelium or in coliform population, even after a long term intake. On the other
      hand, the histochemical approach revealed significant diet-related changes in
      mucin amounts in the duodenum. In particular, the percentage of villous area
      occupied by acidic and sulpho-mucin granules decreased from controls to GM-fed
      animals, whereas neutral mucins did not change.

PMID- 20819775
TI  - Effects of hypophyseal or thymic allograft on thymus development in partially
      decerebrate chicken embryos: expression of PCNA and CD3 markers.
AB  - Changes in chicken embryo thymus after partial decerebration (including the
      hypophysis) and after hypophyseal or thymic allograft were investigated. Chicken
      embryos were partially decerebrated at 36-40 hr of incubation and on day 12
      received a hypophysis or a thymus allograft from 18-day-old donor embryos. The
      thymuses of normal, sham-operated and partially decerebrate embryos were
      collected on day 12 and 18. The thymuses of the grafted embryos were collected on
      day 18. The samples were examined with histological method and tested for the
      anti-PCNA and anti-CD3 immune-reactions. After partial decerebration, the thymic
      cortical and medullary compartments diminished markedly in size. Anti-PCNA and
      anti-CD3 revealed a reduced immune-reaction, verified also by statistical
      analysis. In hypophyseal or grafted embryos, the thymic morphological
      compartments improved, the anti-PCNA and anti-CD3 immune-reactions recovered much
      better after the thymic graft, probably due to the thymic growth factors and also
      by an emigration of thymocytes from the same grafted thymus.

PMID- 20819776
TI  - Histopathological and immunohistochemical study of the hepatic lesions
      experimentally induced by Entamoeba dispar.
AB  - The sequence of hepatic necrotic-inflammatory events produced by Entamoeba dispar
      are originally described in this work. For the first time were described in
      details the experimental lesions produced by E. dispar, as well as the
      distribution of the trophozoites detected by the immunohistochemistry. Animals
      experimentally infected with E. dispar presented necrosis, thrombosis and chronic
      granulomatous inflammation. Immunoreactive products derived from trofozoites were
      observed close or associated with trophozoites, epithelioid cells, leucocytes and
      hepatocytes. Few are the articles on the literature about virulence of E. dispar,
      which is approximately 9 times more frequent than to E. histolytica. Variation in
      the virulence is, therefore expected and signalizing the need of the continuity
      of studies with E. dispar strains from different places in the world. Taking into
      account that E. dispar is a closely related species to E. histolytica, these
      studies could determine new elements involved with E. histolytica pathogenesis,
      helping us to understand better the disease.

PMID- 20819777
TI  - In memoriam of Prof. Maria Gabriella Manfredi Romanini.

PMID- 20819779
TI  - The role of inflammation in HPV carcinogenesis.
AB  - The role of inflammation in human papillomavirus (HPV) infection and disease is
      complex since it involves responses capable of preventing initial infections,
      clearing those ongoing as well as promoting persistence and progression of
      associated lesions. Avoiding the immune response has been considered a key aspect
      of HPV persistence which is the main factor leading to HPV-related neoplasia.
      HPVs have evolved different ways of targeting immune signaling pathways.
      Moreover, host inflammatory response may promote lesion progression and affect
      tumor fate by diverse mechanisms including the direct participation of
      inflammatory cells. In this review, we discuss the interplay between HPV
      oncogenic proteins and an array of inflammatory responses that ultimately may
      lead to cancer.

PMID- 20819778
TI  - MicroRNA-related genetic variations as predictors for risk of second primary
      tumor and/or recurrence in patients with early-stage head and neck cancer.
AB  - Second primary tumor (SPT) and/or recurrence negatively impact the prognosis of
      patients with curatively treated early-stage head and neck cancer. MicroRNAs
      (miRNAs) play important roles in cancer development. We explored whether the
      variations of miRNA-related pathway were associated with the risk of
      SPT/recurrence in patients with early-stage head and neck cancer. This study
      includes 150 early-stage head and neck cancer patients with SPT/recurrence and
      300 patients without SPT/recurrence. Two hundred and thirty-five tagging and
      potentially functional single-nucleotide polymorphisms (SNPs) were genotyped from
      eight miRNA biogenesis pathway genes and 135 miRNA-targeted genes. Eighteen miRNA
      related SNPs were significantly associated with the risk of SPT/recurrence. The
      most significant SNP was rs3747238, a miRNA-binding site SNP in SMC1B. The
      variant homozygous genotype of this SNP was associated with a 1.74-fold increased
      risk [95% confidence interval (CI) 1.19-2.54; P = 0.004]. Cumulative effect
      analysis showed joint effects for the number of unfavorable genotype in patients.
      Survival tree analysis further identified the high-order gene-gene interactions
      and categorized the study subjects into low-, medium- and high-risk groups.
      Patients in the high-risk group had a 4.84-fold increased risk (95% CI: 3.11
      7.51; P = 2.45 * 10(-12)) and a shorter event-free median survival time of 37.9
      months (log rank P = 2.28 * 10(-13)). Our results suggested that miRNA-related
      genetic polymorphisms may be used individually and jointly to predict the risk of
      SPT/recurrence of early-stage head and neck cancer patients.

PMID- 20819781
TI  - Toward a coherent account of pediatric decision making.
AB  - Within and among societies, there are competing understandings of the status of
      children, including debates over whether they can bear rights and, if so, which
      rights they bear and against whom, and their capacity to make decisions and be
      held responsible and accountable for actions. There also are different
      understandings of what constitutes a family; what authority parents have over and
      regarding their children; and what should happen to children who are without
      parents because of death, desertion, or imprisonment. These and other related
      debates reflect deep differences in worldviews, in how one understands the
      legitimate role of the state, in how one comes to know the proper way to raise
      children, and so on. The United Nations Convention on the Rights of the Child
      purports to reflect international convergence on the rights of children, on how
      decisions concerning children should be made, and on how children ought to be
      treated by the state and by their parents. This paper examines whether the
      Convention's framework for decision making concerning children is an appropriate
      framework for pediatric bioethics. Questions about how to make health care
      decisions for children ultimately are questions of who is in authority to make
      and judge such decisions. Establishing who is in authority, determining whether
      there are any limits to that authority and, if so, defining those limits should
      be the focus of efforts to develop and implement a pediatric decision-making
      framework.

PMID- 20819782
TI  - Malocclusion characteristics of patients with cleft lip and/or palate.
AB  - This study aimed to evaluate the malocclusions of patients with a cleft lip
      and/or palate (CLP) and to compare malocclusion characteristics between subjects
      with a pre-foramen incisor cleft (PIC) and a trans-foramen incisor cleft (TIC). A
      cross-sectional study was conducted of 117 cleft patients (53 per cent male) aged
      6-37 years (mean age 14.7 +/- 7.4 years) who attended the Dental Specialty Center
      in the city of Fortaleza, Brazil, between 2004 and 2007. Oral clefts were
      classified and radiographic examinations and dental casts were analysed to
      determine malocclusions and facial patterns. Malocclusion measurements were
      compared between the PIC and TIC groups by Mann-Whitney and Fisher's exact tests.
      The percentage of subjects with PIC, TIC, post-foramen incisor cleft, and rare
      cleft were 20.5, 73.5, 5.1, and 0.9 per cent, respectively. The prevalence of
      malocclusions in subjects with a CLP was 82.1 per cent (molar relationships
      Classes II and III) in 6- to 12-year-olds, and a severe malocclusion [dental
      aesthetic index (DAI)] was observed in all patients aged 13 years and above. The
      frequency of patients with a normal canine relationship, open bite, and anterior
      crossbite was higher in the PIC group than in the TIC group (6-12 years).
      Patients aged 13 years and above in the PIC group showed lower means for the
      largest anterior maxillary irregularity, higher means for positive anterior
      mandibular overjet, a lower frequency of crowding in the anterior incisal
      segments, and a normal antero-posterior molar relationship compared with the TIC
      group. Severe malocclusions were prevalent in subjects with a CLP. Subjects with
      a TIC have higher prevalence of malocclusions than those with a PIC.

PMID- 20819783
TI  - Survival and success of maxillary canine autotransplantation: a retrospective
      investigation.
AB  - The aim of this study was to evaluate survival and success rates following
      autotransplantation of permanent maxillary canine teeth. Sixty-three cases of
      maxillary canine autotransplantation from 49 subjects (mean age at
      transplantation 21.8 years, range 13-42.1 years) undertaken between 1977 and 2003
      were collected as part of an audit project of transplantation success. All
      maxillary canines had complete root development at the time of transplantation.
      The sample was divided into two groups, a matched case-control study to compare
      27 unilateral transplanted canines with the non-transplanted canine on the
      contralateral side, and all 63 transplanted canines with no controls. Teeth were
      assessed clinically using established criteria for success: tooth presence for
      survival and resorption, mobility, probing pocket depth (PPD), gingival bleeding,
      vitality, and colour. Radiographic investigation for success assessed internal
      and external inflammatory resorption (including the amount) bone levels and any
      signs of pathology. Data were described with descriptive statistics and
      analytical tests were used to assess frequencies of occurrence. The survival rate
      was 83 per cent with an average duration of 14.5 years in situ. Thirty-eight per
      cent of the transplants were deemed successful. There were statistically
      significant associations between the transplanted and non-transplanted teeth in
      PPD (P = 0.006), gingival bleeding (P = 0.006), vitality (P = 0.004), and colour
      (P = 0.002). Autotransplantation of impacted maxillary canines can be successful
      in the long term and may be indicated in selected cases. Although the rate for
      complete success in this study was low (no signs of resorption, mobility, and
      sound periodontal tissues), the survival rate can be considered favourable when
      evaluating autotransplantation as a treatment option for grossly malpositioned
      canines with little scope for orthodontic alignment.

PMID- 20819784
TI  - Epidemiology-based risk assessment using the benchmark dose/margin of exposure
      approach: the example of ethanol and liver cirrhosis.
AB  - BACKGROUND: A novel approach to derive a threshold dose with respect to alcohol
      related harm, the benchmark dose (BMD) methodology, is introduced to provide a
      basis for evidence-based drinking guidelines. This study is the first to
      calculate a BMD for alcohol exposure using epidemiological cohort data. With this
      BMD we will be able to calculate the margin of exposure (MOE) for alcohol
      consumption, which can be used for comparative risk assessment and applied to
      setting public health policy. METHODS: Benchmark dose-response modelling of
      epidemiological data gathered during a recent systematic review and meta-analysis
      of alcohol consumption as a risk factor for liver cirrhosis morbidity and
      mortality. RESULTS: For a benchmark response (BMR) of 1.5%, the resulting BMD
      values were 30.9 g/day for males and 29.7 g/day for females; the corresponding
      lower one-sided confidence values were 25.7 and 27.2 g/day, respectively. The
      intake scenario for the Canadian population resulted in an MOE of 1.23. Intake
      scenarios for individuals as based on the Canadian drinking guidelines led to MOE
      values between 0.96 and 1.91. Using an uncertainty factor of 10, the acceptable
      daily intake for alcohol would be 2.6 g/day. CONCLUSIONS: The BMD approach was
      feasible in developing evidence-based guidelines for low-risk drinking. As our
      calculated MOEs result around unity (i.e. 1) for moderate drinking, it is evident
      that the current guidelines correspond very well to low risk on the dose-response
      curve. The BMD methodology therefore validates current guidelines. The results
      again highlight the health risk associated with alcohol consumption.

PMID- 20819785
TI  - Body mass trajectories through adulthood: results from the National Longitudinal
      Survey of Youth 1979 Cohort (1981-2006).
AB  - BACKGROUND: Most studies describing change in body mass through adulthood model
      an 'average' trajectory bearing the same functional form in the underlying
      population. Latent-class growth modelling has revealed the presence of several
      underlying body mass/obesity trajectory groups among children and adolescents,
      but has not been applied to capture adult body mass trajectories. We apply the
      technique to identify adult body mass trajectory groups, risk factors for group
      membership and (time-varying) modifiers of trajectory level within each group,
      and assess association between group membership and important health outcomes in
      midlife. METHODS: Body mass trajectory groups, from age 18 to 49 years, were
      identified using latent-class growth modelling based on the National Longitudinal
      Survey of Youth 1979 (n = 9681). Role of gender, race/ethnicity and age cohort as
      risk factors for group membership, and of highest grade of education completed,
      years of urban living, years in employment, years in poverty and years married as
      modifiers of trajectory level was evaluated. RESULTS: Four trajectory groups,
      'normal weight', 'overweight', 'late adulthood obesity' and 'early adulthood
      obesity' were identified. Males, Blacks and those born later had higher odds of
      being in the three latter groups. More education and years married lowered the
      trajectory within each group. The prevalence of most health outcomes was lowest
      in the 'normal weight' group, somewhat greater in the 'overweight' group, greater
      again in the 'late adult obesity group' and highest in the 'early adulthood
      obesity' group. CONCLUSION: Regular body mass index screening and monitoring in
      early adult life may identify a person as belonging to one of these four groups
      early, and allow the individual and health-care providers opportunities to
      initiate behavioural or other interventions better tailored to the specific
      group.

PMID- 20819786
TI  - Cohort profile: the Melbourne Longitudinal Studies on Healthy Ageing Program.

PMID- 20819780
TI  - First-line bevacizumab plus taxane-based chemotherapy for locally recurrent or
      metastatic breast cancer: safety and efficacy in an open-label study in 2,251
      patients.
AB  - BACKGROUND: First-line bevacizumab combined with chemotherapy significantly
      improves efficacy versus chemotherapy alone in human epidermal growth factor
      receptor 2 (HER2)-negative locally recurrent or metastatic breast cancer
      (LR/mBC). This large, open-label study further assesses first-line bevacizumab
      with taxane-based chemotherapy in routine oncology practice. PATIENTS AND
      METHODS: Patients with HER2-negative LR/mBC, Eastern Cooperative Oncology Group
      (ECOG) performance status (PS) of zero to two and no prior chemotherapy for
      LR/mBC received bevacizumab 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks plus
      taxane-based chemotherapy (or other non-anthracycline chemotherapy) until disease
      progression, unacceptable toxicity or patient withdrawal. The primary end point
      was safety; time to progression (TtP) was a secondary end point. RESULTS: Median
      follow-up in 2251 treated patients was 12.7 months. Median age was 53 years and
      94% of patients had ECOG PS of zero or one. Bevacizumab was most commonly
      administered with single-agent paclitaxel (35%), single-agent docetaxel (33%) or
      taxane-based combination therapy (10%). The most frequent grade >=3 adverse event
      (AE) was neutropenia (5.4%). Grade >=3 AEs previously associated with bevacizumab
      included hypertension (4.4%), arterial/venous thromboembolism (3.2%), proteinuria
      (1.7%) and bleeding (1.4%). No new bevacizumab safety signals were observed.
      Median TtP was 9.5 months (95% confidence interval 9.1-9.9). CONCLUSIONS: The
      study population in ATHENA was more representative of general oncology practice
      than populations enrolled into randomised trials, although there may have been
      some bias towards younger, fitter patients. The safety and efficacy of
      bevacizumab-taxane therapy in this large study were consistent with results from
      randomised first-line trials.

PMID- 20819788
TI  - Using genetic mapping and genomics approaches in understanding and improving
      drought tolerance in pearl millet.
AB  - Drought at the reproductive stage is a major constraint to pearl millet
      [Pennisetum glaucum (L.) R. Br.] productivity. Quantitative trait locus (QTL)
      mapping provides a means to dissect complex traits, such as drought tolerance,
      into their components, each of which is controlled by QTLs. Molecular marker
      supported genotypic information at the identified QTLs then enables quick and
      accurate accumulation of desirable alleles in plant breeding programmes. Recent
      genetic mapping research in pearl millet has mapped several QTLs for grain yield
      and its components under terminal drought stress conditions. Most importantly, a
      major QTL associated with grain yield and for the drought tolerance of grain
      yield in drought stress environments has been identified on linkage group 2 (LG
      2) which accounts for up to 32% of the phenotypic variation of grain yield in
      mapping population testcrosses. The effect of this QTL has been validated in two
      independent marker-assisted backcrossing programmes, where 30% improvement in
      grain yield general combining ability (GCA) expected of this QTL under terminal
      drought stress conditions was recovered in the QTL introgression lines. To
      transfer effectively favourable alleles of this QTL into pearl millet varieties
      that otherwise are high yielding and adapted to specific agricultural zones,
      efforts are currently underway to develop closely spaced gene-based markers
      within this drought tolerance (DT)-QTL. In this review, an overview is provided
      of information on the genetic maps developed in pearl millet for mapping drought
      tolerance traits and their applications in identifying and characterizing DT
      QTLs. Marker-assisted transfer of desirable QTL alleles to elite parent
      backgrounds, and results from introgression line validation in multiple terminal
      drought stress environments are discussed. Current efforts undertaken towards
      delimiting the interval of a major DT-QTL mapping to LG 2, and towards
      identifying candidate genes and physiologies underlying this QTL are presented.
      Highly specialized genetic stocks [QTL-near-isogenic lines (NILs), a high
      resolution cross, and a germplasm population] and genomic resources (gene
      sequences, gene-based markers, and comparative genomics information) specifically
      developed for these purposes are discussed.

PMID- 20819787
TI  - Smoking cessation: predictive factors among middle-aged Japanese.
AB  - INTRODUCTION: No studies have been conducted in Asia to examine predictors for
      smoking cessation by long-term follow-up of smokers. We sought to examine
      predictors for smoking cessation in Japanese subjects using baseline and 10-year
      follow-up data of the Japan Public Health Center-based Prospective Study (JPHC
      Study) Cohort I. METHODS: We calculated adjusted odds ratios of predictors for
      smoking cessation with a cohort of 9,524 Japanese men and women aged 40-59 years
      who were smokers at baseline (1990) and for whom smoking status information at 10
      year follow-up (2000) was available. RESULTS: At follow-up, 24.9% of smokers had
      stopped smoking. White-collar workers were more likely to cease than blue-collar
      ones; the multivariate odds ratio (OR) was 1.18 (95% CI: 1.05-1.32). The
      multivariate OR of smoking cessation for initiation of a prescribed drug and that
      of disease development was 1.92 (95% CI: 1.72-2.14) and 1.21 (95% CI: 1.08-1.36),
      respectively. Those smoking more cigarettes and who started smoking at a young
      age were less likely to stop smoking. Older age, physical activity, and
      participation in health checkups were associated with smoking cessation. Gender
      was not a significant predictor after adjustment for other factors. DISCUSSION:
      In a large follow-up study of middle-aged Japanese smokers, the predictors of
      smoking cessation were age, job, smoking habit, physical activity, health checkup
      participation, and health status.

PMID- 20819789
TI  - Functional characterization of the HD-ZIP IV transcription factor OCL1 from
      maize.
AB  - OCL1 (OUTER CELL LAYER1) encodes a maize HD-ZIP class IV transcription factor
      (TF) characterized by the presence of a homeo DNA-binding domain (HD), a
      dimerization leucine zipper domain (ZIP), and a steroidogenic acute regulatory
      protein (StAR)-related lipid transfer domain (START) involved in lipid transport
      in animals but the function of which is still unknown in plants. By combining
      yeast and plant trans-activation assays, the transcriptional activation domain of
      OCL1 was localized to 85 amino acids in the N-terminal part of the START domain.
      Full-length OCL1 devoid of this activation domain is unable to trans-activate a
      reporter gene under the control of a minimal promoter fused to six repeats of the
      L1 box, a cis-element present in target genes of HD-ZIP IV TFs in Arabidopsis. In
      addition, ectopic expression of OCL1 leads to pleiotropic phenotypic aberrations
      in transgenic maize plants, the most conspicuous one being a strong delay in
      flowering time which is correlated with the misexpression of molecular markers
      for floral transition such as ZMM4 (Zea Mays MADS-box4) or DLF1 (DELAYED
      FLOWERING1). As suggested by the interaction in planta between OCL1 and SWI3C1, a
      bona fide subunit of the SWI/SNF complex, OCL1 may modulate transcriptional
      activity of its target genes by interaction with a chromatin remodelling complex.

PMID- 20819791
TI  - Characterization of volatile production during storage of lettuce (Lactuca
      sativa) seed.
AB  - The duration that seeds stay vigorous during storage is difficult to predict but
      critical to seed industry and conservation communities. Production of volatile
      compounds from lettuce seeds during storage was investigated as a non-invasive
      and early detection method of seed ageing rates. Over 30 volatile compounds were
      detected from lettuce seeds during storage at 35 degrees C at water contents
      ranging from 0.03 to 0.09 g H(2)O g(-1) dw. Both qualitative and quantitative
      differences in volatile composition were noted as a function of water content,
      and these differences were apparent before signs of deterioration were visible.
      Seeds stored at high water content (L >or=0.06 g H(2)O g(-1) dw) emitted
      molecular species indicative of glycolysis (methanol+ethanol), and evidence of
      peroxidation was apparent subsequent to viability loss. Seeds containing less
      water (0.03-0.05 g H(2)O g(-1) dw) produced volatiles indicative of peroxidation
      and survived longer compared with seeds stored under more humid conditions.
      Production of glycolysis-related by-products correlated strongly with
      deterioration rate when measured as a function of water content. This correlation
      may provide a valuable non-invasive means to predict the duration of the early,
      asymptomatic stage of seed deterioration.

PMID- 20819790
TI  - Megapixel imaging of (micro)nutrients in mature barley grains.
AB  - Understanding the accumulation and distribution of essential nutrients in cereals
      is of primary importance for improving the nutritional quality of this staple
      food. While recent studies have improved the understanding of micronutrient
      loading into the barley grain, a detailed characterization of the distribution of
      micronutrients within the grain is still lacking. High-definition synchrotron X
      ray fluorescence was used to investigate the distribution and association of
      essential elements in barley grain at the micro scale. Micronutrient distribution
      within the scutellum and the embryo was shown to be highly variable between
      elements in relation to various morphological features. In the rest of the grain,
      the distribution of some elements such as Cu and Zn was not limited to the
      aleurone layer but extended into the endosperm. This pattern of distribution was
      less marked in the case of Fe and, in particular, Mn. A significant difference in
      element distribution was also found between the ventral and dorsal part of the
      grains. The correlation between the elements was not consistent between and
      within tissues, indicating that the transport and storage of elements is highly
      regulated. The complexity of the spatial distribution and associations has
      important implications for improving the nutritional content of cereal crops such
      as barley.

PMID- 20819792
TI  - Association of CYP19 and ESR1 pleiotropic genes with human longevity.
AB  - Aromatase (CYP19) and estrogen receptor-alpha (ESR1) are involved in the
      metabolism of estrogens, which have a relevant role in female and male aging.
      Moreover, due to their influence on fertility, both genes may be part of the
      longevity-fertility trade-off mechanism. This investigation examines the
      association of ESR1 (PvuII and XbaI) and CYP19 (rs4646) polymorphisms with
      longevity. A sample of 258 individuals (mean age = 83.1 +/- 5.7 years) was
      recruited in 2000. Based on mortality data collected in 2009, the sample was
      divided into two groups of participants surviving more than 90 years or not. The
      analysis showed that ESR1 PP (odds ratio = 2.2) and CYP19 genotypes carrying the
      T allele (odds ratio =  1.9) were significantly associated with longevity
      (survival to age more than 90 years). As the ESR1 PP genotypes were found
      associated with reduced fertility in the same sample, we may infer that ESR1
      genotypes could exert an antagonistic pleiotropic effect on longevity and
      fertility.

PMID- 20819793
TI  - Life extension by diet restriction and N-acetyl-L-cysteine in genetically
      heterogeneous mice.
AB  - We used a heterogeneous stock of mice-UM-HET3, the first generation offspring of
      CByB6F1/J and C3D2F1/J parents-to test effects of six antiaging treatments on
      life span. In the first report of diet restriction in a structured, segregating
      heterogeneous population, we observed essentially the same increases in mean and
      maximum life span as found in CByB6F1/J hybrid positive controls. We also report
      results of treatment with N-acetyl-L-cysteine started at 7 months, and aspirin,
      nitroflurbiprofen, 4-hydroxy phenyl N-tert-butyl nitrone, and
      nordihydroguaiaretic acid, all started at 16-18 months. Only male UM-HET3 mice
      receiving N-acetyl-L-cysteine had significantly increased life span, and this may
      have been due to treatment-related inadvertent diet restriction. The other agents
      had no significant effects on life span. The use of UM-HET3 mice helps assure
      that these results are not the result of unresponsiveness of a single genotype
      but that they more broadly represent laboratory mice.

PMID- 20819794
TI  - Determinants of serum-induced SIRT1 expression in older men: the CHAMP study.
AB  - Circulating factors that have an effect on SIRT1 expression are influenced by
      caloric restriction. To determine the association between frailty and such
      circulating factors, we measured serum-induced SIRT1 expression from a nested
      cohort of frail (n = 77) and robust (n = 82) participants from Concord Health and
      Ageing in Men Project, a population-based study of community-dwelling men older
      than 70 years. Serum-induced SIRT1 expression was not different between frail and
      robust men (103.1 +/- 17.0 versus 100.4 +/- 19.3 MUg/L). However, subsequent
      analyses showed that men with the lowest values (first quartile) were less likely
      to be frail (odds ratio = 0.5, 95% confidence interval = 0.2-1.0, p = .04) and
      had higher total body lean mass (p = .001) than the other participants. Serum
      induced SIRT1 expression did not correlate with age, diseases, medications,
      albumin, fasting glucose, or lipids. Overall, there was no association between
      frailty and serum-induced SIRT1 expression; however, post hoc analysis suggested
      that there might be a paradoxical association between low serum-induced SIRT1
      expression and robustness.

PMID- 20819795
TI  - An unusual phenotype in Muckle-Wells syndrome associated with NLRP3 E311K.

PMID- 20819796
TI  - The skin of patients with systemic sclerosis softened during the treatment with
      anti-IL-6 receptor antibody tocilizumab.
AB  - OBJECTIVE: SSc is an autoimmune disease characterized by fibrosis of the skin and
      internal organs. Although the aetiology remains uncertain, many reports have
      suggested that IL-6 is involved in SSc pathogenesis. Tocilizumab, an anti-IL-6
      receptor antibody, is an anti-arthritis medicine that works through the blockade
      of IL-6 functions. To examine the effect of tocilizumab on SSc, we administered
      tocilizumab to two SSc patients. METHODS: Two dcSSc patients were administered
      tocilizumab at 8 mg/kg once a month for 6 months. One patient had pulmonary
      fibrosis assessed by CT and spirometry, and the other had chronic renal failure
      caused by scleroderma renal crisis. Their skin condition was monitored with a
      Vesmeter and the modified Rodnan total skin score (mRTSS). Skin biopsies were
      obtained before and after the tocilizumab treatment to investigate the
      histological changes. RESULTS: After tocilizumab treatment, both patients showed
      softening of the skin with reductions of 50.7 and 55.7% in the total z-score of
      Vesmeter hardness and 51.9 and 23.0% in the mRTSS, respectively. Histological
      examination showed thinning of the collagen fibre bundles in the dermis. The
      creatinine clearance in the patient with chronic renal failure improved from 38
      to 55 ml/min. However, the fibrotic changes in the lung in the other patient
      remained unchanged. CONCLUSIONS: In the two cases of SSc that we report here,
      softening of the skin was observed during the treatment with tocilizumab.

PMID- 20819797
TI  - Fatigue in rheumatoid arthritis: time for a conceptual model.

PMID- 20819798
TI  - How to predict subclinical atherosclerosis in systemic lupus erythematosus.

PMID- 20819799
TI  - Localized melioidosis in children in Thailand: treatment and long-term outcome.
AB  - Melioidosis, an infection caused by Burkholderia pseudomallei, can present as
      severe septicemia or localized infection. Data on optimum antibiotic treatment
      regimen for localized melioidosis in children is limited. This is a report on
      localized melioidosis in children, regarding clinical presentation, treatment and
      the long-term outcomes. We reviewed 37 cases of localized melioidosis in children
      treated between 1994 and 2006 and followed up them prospectively until 1 October
      2007. The two most common presentations were skin/soft tissue infections and
      suppurative parotitis. Oral eradication antibiotics after initial parenteral
      therapy included trimetroprim-sulfamethoxazole (10 patients) and trimetroprim
      sulfamethoxazole in combination with doxycycline (four patients). Patients who
      did not get any parenteral antibiotics for B. pseudomallei were treated with oral
      trimetroprim-sulfamethoxazole (10 patients) and trimetroprim-sulfamethoxazole in
      combination with doxycycline (one patient). No adverse effects were reported. We
      were able to follow-up 32 patients, all recovered except one patient reported a
      history of possible relapse.

PMID- 20819800
TI  - Clinical and epidemiological characteristics of pandemic influenza A/(H1N1) in
      hospitalized pediatric patients at a university hospital, Istanbul, Turkey.
AB  - BACKGROUND: The aim of this study was to describe the clinical and
      epidemiological characteristics of pandemic influenza in hospitalized children.
      METHODS: A total of 114 patients with suspected H1N1 virus infection were
      hospitalized, and nasal swabs were sent to National Influenza Reference
      Laboratory for confirmation of pandemic influenza A (H1N1) virus infection by rRT
      PCR assay. RESULTS: Forty-six female and 68 male patients were included in the
      study. Age of the patients ranged from 40 days to 16 years. Clinical and/or
      radiological pneumonia were detected in 96% of all. Sixteen patients required
      mechanical ventilation due to hypoxemia. Previously healthy children required
      mechanical ventilation and oxygen therapy more than patients with chronic
      diseases. Elevated levels of CRP and LDH in patients with respiratory distress
      and patients who required mechanical ventilation were statistically significant.
      CONCLUSION: Our study showed that progress of pandemic influenza infection in
      previously healthy children is as severe as their counterparts with chronic
      underlying diseases.

PMID- 20819801
TI  - Short-term follow-up of HIV-1 infected children without treatment: use of CD4/CD8
      ratio as a marker of disease progression.

PMID- 20819802
TI  - Mental health among commando, airborne and other UK infantry personnel.
AB  - BACKGROUND: Despite having high levels of combat exposure, commando and airborne
      forces may be at less risk of mental ill-health than other troops. AIMS: To
      examine differences in mental health outcomes and occupational risk factors
      between Royal Marines Commandos (RMCs), paratroopers (PARAs) and other army
      infantry (INF). METHODS: Three groups of personnel (275 RMCs, 202 PARAs and 572
      INF) were generated from a UK military cohort study of personnel serving at the
      time of the 2003 Iraq war. Participants completed a questionnaire about their
      mental health and experiences on deployment. Differences in mental health
      outcomes between the groups were examined with logistic regression and negative
      binomial regression analyses. RESULTS: Both RMCs and PARAs were less likely to
      have multiple physical symptoms or to be fatigued, and RMCs also had lower levels
      of general mental health problems and lower scores on the Post-traumatic
      Checklist than INF personnel. Differences were not explained by the level of unit
      cohesion. CONCLUSIONS: The effect of warfare on troops' well-being is not
      universal across occupational groups. A possible explanation for this difference
      is that the high level of preparedness in RMCs and PARAs may lessen the
      psychological impact of war-zone deployment experiences.

PMID- 20819804
TI  - Respiratory health of municipal solid waste workers.
AB  - BACKGROUND: There is an increasing evidence that the incidence of work-related
      pulmonary problems is greater in waste collectors than in the general workforce.
      AIMS: To evaluate the respiratory health of municipal solid waste workers
      (MSWWs). METHODS: One hundred and eighty-four municipal employees of Keratsini
      (104 MSWWs and 80 controls) participated in a cross-sectional study. All
      participants were asked to fill in a slightly modified version of the Medical
      Research Council questionnaire. Lung function was evaluated by spirometry.
      RESULTS: Spirometry revealed reduced mean forced vital capacity (FVC) and forced
      expiratory volume in 1 s (as a percentage of predicted values) in MSWWs compared
      with controls. After adjustment for smoking status, only the decline in FVC was
      statistically significant (P < 0.05). Prevalence of all respiratory symptoms was
      higher in MSWWs than in controls. After adjustment for confounding factors, the
      difference reached statistical significance (P < 0.05) for morning cough, cough
      on exertion and sore throat. CONCLUSIONS: The results of this cross-sectional
      study indicate a higher prevalence of respiratory symptoms and a greater decrease
      in lung function in MSWWs. A number of limitations such as the relatively small
      size of population and the 'healthy worker' effect should be taken into account.

PMID- 20819803
TI  - Volatile organic compounds exposure and cardiovascular effects in hair salons.
AB  - BACKGROUND: The relationship between occupational exposures to volatile organic
      compounds (VOCs) and cardiovascular effects among hairdressing assistants has not
      been well characterized. AIMS: To investigate whether or not exposure to VOCs was
      associated with autonomic dysfunction, inflammation and oxidative stress in
      hairdressing assistants. METHODS: We recruited 62 young healthy assistants
      working in different hair salons in Taipei. Blood samples were taken from each
      assistant and heart rate variability (HRV) indices were recorded. VOCs were
      measured at each assistant's workplace. Mixed-effects models were used to examine
      the association between blood markers, HRV and VOCs. RESULTS: Exposure to VOCs
      was associated with increases in serum C-reactive protein (CRP) and 8-hydroxy-2'
      deoxyguanosine (8-OHdG) as well as decreases in HRV indices. The effect of VOCs
      exposure on the health parameters measured in this study was greatest during the
      days on which the subjects were working. CONCLUSIONS: Occupational exposure to
      VOCs in hair salons can lead to increases in serum CRP and 8-OHdG levels and
      decreases in HRV indices. Time spent away from the workplace could modify the
      effects these exposures have on the health parameters described above in these
      assistants.

PMID- 20819805
TI  - A new approach to evaluating the well-being of police.
AB  - BACKGROUND: There is a growing body of evidence that links employee well-being to
      organizational performance. Although police forces are under increasing pressure
      to improve efficiency and productivity, the evaluation of well-being in law
      enforcement is mostly restricted to self-report stress questionnaires that are
      based on questionable construction methodologies. No instrument to specifically
      determine the well-being of police force employees currently exists. AIMS: To
      construct an instrument that measures the work-related well-being of officers and
      staff within a police force. METHODS: The approach is drawn from well-established
      clinical models used to evaluate the well-being of patients. Potential variables
      were confirmed using an item selection method known as impact analysis that
      places keen emphasis on frequency and importance as perceived by the respondents
      themselves. RESULTS: Analyses of 822 completed response sets showed that nine
      separate dimensions of police work can adversely affect well-being (advancement,
      facilities, home work interface, job, physical health, psychological health,
      relationships, organizational and workload). Overall, officers showed inferior
      well-being compared with their colleagues. Content validity and adequate internal
      reliability were confirmed. CONCLUSIONS: This study considered a new robust
      approach to evaluating the well-being of all those working in law enforcement.
      The nine dimensions extended beyond conventional stress measures and may offer a
      practical alternative way of assessing the overall well-being status of an entire
      force using a systematic item selection framework.

PMID- 20819806
TI  - Toward a synthetic understanding of the role of phenology in ecology and
      evolution.
AB  - Phenology affects nearly all aspects of ecology and evolution. Virtually all
      biological phenomena-from individual physiology to interspecific relationships to
      global nutrient fluxes-have annual cycles and are influenced by the timing of
      abiotic events. Recent years have seen a surge of interest in this topic, as an
      increasing number of studies document phenological responses to climate change.
      Much recent research has addressed the genetic controls on phenology, modelling
      techniques and ecosystem-level and evolutionary consequences of phenological
      change. To date, however, these efforts have tended to proceed independently.
      Here, we bring together some of these disparate lines of inquiry to clarify
      vocabulary, facilitate comparisons among habitat types and promote the
      integration of ideas and methodologies across different disciplines and scales.
      We discuss the relationship between phenology and life history, the distinction
      between organismal- and population-level perspectives on phenology and the
      influence of phenology on evolutionary processes, communities and ecosystems.
      Future work should focus on linking ecological and physiological aspects of
      phenology, understanding the demographic effects of phenological change and
      explicitly accounting for seasonality and phenology in forecasts of ecological
      and evolutionary responses to climate change.

PMID- 20819807
TI  - Phenology, seasonal timing and circannual rhythms: towards a unified framework.
AB  - Phenology refers to the periodic appearance of life-cycle events and currently
      receives abundant attention as the effects of global change on phenology are so
      apparent. Phenology as a discipline observes these events and relates their
      annual variation to variation in climate. But phenology is also studied in other
      disciplines, each with their own perspective. Evolutionary ecologists study
      variation in seasonal timing and its fitness consequences, whereas
      chronobiologists emphasize the periodic nature of life-cycle stages and their
      underlying timing programmes (e.g. circannual rhythms). The (neuro-) endocrine
      processes underlying these life-cycle events are studied by physiologists and
      need to be linked to genes that are explored by molecular geneticists. In order
      to fully understand variation in phenology, we need to integrate these different
      perspectives, in particular by combining evolutionary and mechanistic approaches.
      We use avian research to characterize different perspectives and to highlight
      integration that has already been achieved. Building on this work, we outline a
      route towards uniting the different disciplines in a single framework, which may
      be used to better understand and, more importantly, to forecast climate change
      impacts on phenology.

PMID- 20819809
TI  - Why does phenology drive species distribution?
AB  - Despite the numerous studies which have been conducted during the past decade on
      species ranges and their relationship to the environment, our understanding of
      how environmental conditions shape species distribution is still far from
      complete. Yet, some process-based species distribution models have been able to
      simulate plants and insects distribution at a global scale. These models strongly
      rely on the completion of the annual cycle of the species and therefore on their
      accomplished phenology. In particular, they have shown that the northern limit of
      species' ranges appears to be caused mainly by the inability to undergo full
      fruit maturation, while the southern limit appears to be caused by the inability
      to flower or unfold leaves owing to a lack of chilling temperatures that are
      necessary to break bud dormancy. I discuss here why phenology is a key adaptive
      trait in shaping species distribution using mostly examples from plant species,
      which have been the most documented. After discussing how phenology is involved
      in fitness and why it is an adaptive trait susceptible to evolve quickly in
      changing climate conditions, I describe how phenology is related to fitness in
      species distribution process-based models and discuss the fate of species under
      climate change scenarios using model projections and experimental or field
      studies from the literature.

PMID- 20819808
TI  - Genetic and physiological bases for phenological responses to current and
      predicted climates.
AB  - We are now reaching the stage at which specific genetic factors with known
      physiological effects can be tied directly and quantitatively to variation in
      phenology. With such a mechanistic understanding, scientists can better predict
      phenological responses to novel seasonal climates. Using the widespread model
      species Arabidopsis thaliana, we explore how variation in different genetic
      pathways can be linked to phenology and life-history variation across
      geographical regions and seasons. We show that the expression of phenological
      traits including flowering depends critically on the growth season, and we
      outline an integrated life-history approach to phenology in which the timing of
      later life-history events can be contingent on the environmental cues regulating
      earlier life stages. As flowering time in many plants is determined by the
      integration of multiple environmentally sensitive gene pathways, the novel
      combinations of important seasonal cues in projected future climates will alter
      how phenology responds to variation in the flowering time gene network with
      important consequences for plant life history. We discuss how phenology models in
      other systems--both natural and agricultural--could employ a similar framework to
      explore the potential contribution of genetic variation to the physiological
      integration of cues determining phenology.

PMID- 20819810
TI  - Phenological asynchrony between herbivorous insects and their hosts: signal of
      climate change or pre-existing adaptive strategy?
AB  - Climate change alters phenological relations between interacting species. We
      might expect the historical baseline, or starting-point, for such effects to be
      precise synchrony between the season at which a consumer most requires food and
      the time when its resources are most available. We synthesize evidence that
      synchrony was not the historical condition in two insect-plant interactions
      involving Edith's checkerspot butterfly (Euphydryas editha), the winter moth
      (Operophtera brumata) and their host plants. Initial observations of phenological
      mismatch in both systems were made prior to the onset of anthropogenically driven
      climate change. Neither species can detect the phenology of its host plants with
      precision. In both species, evolution of life history has involved compromise
      between maximizing fecundity and minimizing mortality, with the outcome being
      superficially maladaptive strategies in which many, or even most, individuals die
      of starvation through poor synchrony with their host plants. Where phenological
      asynchrony or mismatch with resources forms the starting point for effects of
      anthropogenic global warming, consumers are particularly vulnerable to impacts
      that exacerbate the mismatch. This vulnerability likely contributed to extinction
      of a well-studied metapopulation of Edith's checkerspot, and to the skewed
      geographical pattern of population extinctions underlying a northward and upward
      range shift in this species.

PMID- 20819812
TI  - Flowering phenology, fruiting success and progressive deterioration of
      pollination in an early-flowering geophyte.
AB  - Spatio-temporal patterns of snowmelt and flowering times affect fruiting success
      in Erythronium grandiflorum Pursh (Liliaceae) in subalpine western Colorado, USA.
      From 1990 to 1995, I measured the consistency across years of snowmelt patterns
      and flowering times along a permanent transect. In most years since 1993, I have
      monitored fruit set in temporal cohorts (early- to late-flowering groups of
      plants) at one site. To assess 'pollination limitation', I have also conducted
      supplemental hand-pollination experiments at various times through the blooming
      season. The onset of blooming is determined by snowmelt, with the earliest years
      starting a month before the latest years owing to variation in winter snowpack
      accumulation. Fruit set is diminished or prevented entirely by killing frosts in
      some years, most frequently but not exclusively for the earlier cohorts. When
      frosts do not limit fruit set, pollination limitation is frequent, especially in
      the earlier cohorts. Pollination limitation is strongest for middle cohorts: it
      tends to be negated by frost in early cohorts and ameliorated by continuing
      emergence of bumble-bee queens in later cohorts. This lily appears to be poorly
      synchronized with its pollinators. Across the years of the study, pollination
      limitation appears to be increasing, perhaps because the synchronization is
      getting worse.

PMID- 20819811
TI  - The effects of phenological mismatches on demography.
AB  - Climate change is altering the phenology of species across the world, but what
      are the consequences of these phenological changes for the demography and
      population dynamics of species? Time-sensitive relationships, such as migration,
      breeding and predation, may be disrupted or altered, which may in turn alter the
      rates of reproduction and survival, leading some populations to decline and
      others to increase in abundance. However, finding evidence for disrupted
      relationships, or lack thereof, and their demographic effects, is difficult
      because the necessary detailed observational data are rare. Moreover, we do not
      know how sensitive species will generally be to phenological mismatches when they
      occur. Existing long-term studies provide preliminary data for analysing the
      phenology and demography of species in several locations. In many instances,
      though, observational protocols may need to be optimized to characterize timing
      based multi-trophic interactions. As a basis for future research, we outline some
      of the key questions and approaches to improving our understanding of the
      relationships among phenology, demography and climate in a multi-trophic context.
      There are many challenges associated with this line of research, not the least of
      which is the need for detailed, long-term data on many organisms in a single
      system. However, we identify key questions that can be addressed with data that
      already exist and propose approaches that could guide future research.

PMID- 20819813
TI  - The importance of phylogeny to the study of phenological response to global
      climate change.
AB  - Climate change has resulted in major changes in the phenology--i.e. the timing of
      seasonal activities, such as flowering and bird migration--of some species but
      not others. These differential responses have been shown to result in ecological
      mismatches that can have negative fitness consequences. However, the ways in
      which climate change has shaped changes in biodiversity within and across
      communities are not well understood. Here, we build on our previous results that
      established a link between plant species' phenological response to climate change
      and a phylogenetic bias in species' decline in the eastern United States. We
      extend a similar approach to plant and bird communities in the United States and
      the UK that further demonstrates that climate change has differentially impacted
      species based on their phylogenetic relatedness and shared phenological
      responses. In plants, phenological responses to climate change are often shared
      among closely related species (i.e. clades), even between geographically disjunct
      communities. And in some cases, this has resulted in a phylogenetically biased
      pattern of non-native species success. In birds, the pattern of decline is
      phylogenetically biased but is not solely explained by phenological response,
      which suggests that other traits may better explain this pattern. These results
      illustrate the ways in which phylogenetic thinking can aid in making
      generalizations of practical importance and enhance efforts to predict species'
      responses to future climate change.

PMID- 20819814
TI  - The annual cycles of phytoplankton biomass.
AB  - Terrestrial plants are powerful climate sentinels because their annual cycles of
      growth, reproduction and senescence are finely tuned to the annual climate cycle
      having a period of one year. Consistency in the seasonal phasing of terrestrial
      plant activity provides a relatively low-noise background from which phenological
      shifts can be detected and attributed to climate change. Here, we ask whether
      phytoplankton biomass also fluctuates over a consistent annual cycle in lake,
      estuarine-coastal and ocean ecosystems and whether there is a characteristic
      phenology of phytoplankton as a consistent phase and amplitude of variability. We
      compiled 125 time series of phytoplankton biomass (chlorophyll a concentration)
      from temperate and subtropical zones and used wavelet analysis to extract their
      dominant periods of variability and the recurrence strength at those periods.
      Fewer than half (48%) of the series had a dominant 12-month period of
      variability, commonly expressed as the canonical spring-bloom pattern. About 20
      per cent had a dominant six-month period of variability, commonly expressed as
      the spring and autumn or winter and summer blooms of temperate lakes and oceans.
      These annual patterns varied in recurrence strength across sites, and did not
      persist over the full series duration at some sites. About a third of the series
      had no component of variability at either the six- or 12-month period, reflecting
      a series of irregular pulses of biomass. These findings show that there is high
      variability of annual phytoplankton cycles across ecosystems, and that climate
      driven annual cycles can be obscured by other drivers of population variability,
      including human disturbance, aperiodic weather events and strong trophic coupling
      between phytoplankton and their consumers. Regulation of phytoplankton biomass by
      multiple processes operating at multiple time scales adds complexity to the
      challenge of detecting climate-driven trends in aquatic ecosystems where the
      noise to signal ratio is high.

PMID- 20819815
TI  - Influence of spring and autumn phenological transitions on forest ecosystem
      productivity.
AB  - We use eddy covariance measurements of net ecosystem productivity (NEP) from 21
      FLUXNET sites (153 site-years of data) to investigate relationships between
      phenology and productivity (in terms of both NEP and gross ecosystem
      photosynthesis, GEP) in temperate and boreal forests. Results are used to
      evaluate the plausibility of four different conceptual models. Phenological
      indicators were derived from the eddy covariance time series, and from remote
      sensing and models. We examine spatial patterns (across sites) and temporal
      patterns (across years); an important conclusion is that it is likely that
      neither of these accurately represents how productivity will respond to future
      phenological shifts resulting from ongoing climate change. In spring and autumn,
      increased GEP resulting from an 'extra' day tends to be offset by concurrent, but
      smaller, increases in ecosystem respiration, and thus the effect on NEP is still
      positive. Spring productivity anomalies appear to have carry-over effects that
      translate to productivity anomalies in the following autumn, but it is not clear
      that these result directly from phenological anomalies. Finally, the productivity
      of evergreen needleleaf forests is less sensitive to phenology than is
      productivity of deciduous broadleaf forests. This has implications for how
      climate change may drive shifts in competition within mixed-species stands.

PMID- 20819817
TI  - Traffic jams: dynamics and control.
AB  - This introductory paper reviews the current state-of-the-art scientific methods
      used for modelling, analysing and controlling the dynamics of vehicular traffic.
      Possible mechanisms underlying traffic jam formation and propagation are
      presented from a dynamical viewpoint. Stable and unstable motions are described
      that may give the skeleton of traffic dynamics, and the effects of driver
      behaviour are emphasized in determining the emergent state in a vehicular system.
      At appropriate points, references are provided to the papers published in the
      corresponding Theme Issue.

PMID- 20819818
TI  - Fluid-dynamical and microscopic description of traffic flow: a data-driven
      comparison.
AB  - Much work has been done to compare traffic-flow models with reality; so far, this
      has been done separately for microscopic, as well as for fluid-dynamical, models
      of traffic flow. This paper compares directly the performance of both types of
      models to real data. The results indicate that microscopic models, on average,
      seem to have a tiny advantage over fluid-dynamical models; however, one may admit
      that for most applications, the differences between the two are small.
      Furthermore, the relaxation times of the fluid-dynamical models turns out to be
      fairly small, of the order of 2 s, and are comparable with the results for the
      microscopic models. This indicates that the second-order terms are weak; however,
      the calibration results indicate that the speed equation is, in fact, important
      and improves the calibration results of the models.

PMID- 20819816
TI  - Forecasting phenology under global warming.
AB  - As a consequence of warming temperatures around the world, spring and autumn
      phenologies have been shifting, with corresponding changes in the length of the
      growing season. Our understanding of the spatial and interspecific variation of
      these changes, however, is limited. Not all species are responding similarly, and
      there is significant spatial variation in responses even within species. This
      spatial and interspecific variation complicates efforts to predict phenological
      responses to ongoing climate change, but must be incorporated in order to build
      reliable forecasts. Here, we use a long-term dataset (1953-2005) of plant
      phenological events in spring (flowering and leaf out) and autumn (leaf colouring
      and leaf fall) throughout Japan and South Korea to build forecasts that account
      for these sources of variability. Specifically, we used hierarchical models to
      incorporate the spatial variability in phenological responses to temperature to
      then forecast species' overall and site-specific responses to global warming. We
      found that for most species, spring phenology is advancing and autumn phenology
      is getting later, with the timing of events changing more quickly in autumn
      compared with the spring. Temporal trends and phenological responses to
      temperature in East Asia contrasted with results from comparable studies in
      Europe, where spring events are changing more rapidly than are autumn events. Our
      results emphasize the need to study multiple species at many sites to understand
      and forecast regional changes in phenology.

PMID- 20819819
TI  - Calibration of microscopic traffic-flow models using multiple data sources.
AB  - Parameter identification of microscopic driving models is a difficult task. This
      is caused by the fact that parameters--such as reaction time, sensitivity to
      stimuli, etc.--are generally not directly observable from common traffic data,
      but also due to the lack of reliable statistical estimation techniques. This
      contribution puts forward a new approach to identifying parameters of car
      following models. One of the main contributions of this article is that the
      proposed approach allows for joint estimation of parameters using different data
      sources, including prior information on parameter values (or the valid range of
      values). This is achieved by generalizing the maximum-likelihood estimation
      approach proposed by the authors in previous work. The approach allows for
      statistical analysis of the parameter estimates, including the standard error of
      the parameter estimates and the correlation of the estimates. Using the
      likelihood-ratio test, models of different complexity (defined by the number of
      model parameters) can be cross-compared. A nice property of this test is that it
      takes into account the number of parameters of a model as well as the
      performance. To illustrate the workings, the approach is applied to two car
      following models using vehicle trajectories of a Dutch freeway collected from a
      helicopter, in combination with data collected with a driving simulator.

PMID- 20819820
TI  - A mechanism to describe the formation and propagation of stop-and-go waves in
      congested freeway traffic.
AB  - This paper introduces a parsimonious theory for congested freeway traffic that
      describes the spontaneous appearance of oscillations and their ensuing
      transformation into stop-and-go waves. Based upon the analysis of detailed
      vehicle-trajectory data, we conclude that timid and aggressive driver behaviours
      are the cause for this transformation. We find that stop-and-go waves arise
      independently of the details of these behaviours. Analytical and simulation
      results are presented.

PMID- 20819821
TI  - Dynamical phenomena induced by bottleneck.
AB  - We study a microscopic follow-the-leader model on a circle of length L with a
      bottleneck. Allowing large bottleneck strengths we encounter very interesting
      traffic dynamics. Different types of waves--travelling and standing waves and
      combinations of both wave types--are observed. The way to find these phenomena
      requires a good understanding of the complex dynamics of the underlying
      (nonlinear) equations. Some of the phenomena, like the ponies-on-a-merry-go-round
      solutions, are mathematically well known from completely different applications.
      Mathematically speaking we use Poincare maps, bifurcation analysis and
      continuation methods beside numerical simulations.

PMID- 20819822
TI  - Stability of car following with human memory effects and automatic headway
      compensation.
AB  - This paper addresses the study of some appropriate control strategies in order to
      guarantee the exponential stability of a class of deterministic microscopic car
      following models including human drivers' memory effects and automated headway
      controllers. More precisely, the delayed action/decision of human drivers is
      represented using distributed delays with a gap and the considered automated
      controller is of proportional derivative type. The analysis is performed in both
      delay parameter and controller gain parameter spaces, and appropriate algorithms
      are proposed. Surprisingly, large delays and/or gains improve stability for the
      corresponding closed-loop schemes. Finally, some illustrative examples as well as
      various interpretations of the results complete the presentation.

PMID- 20819823
TI  - Enhanced intelligent driver model to access the impact of driving strategies on
      traffic capacity.
AB  - With an increasing number of vehicles equipped with adaptive cruise control
      (ACC), the impact of such vehicles on the collective dynamics of traffic flow
      becomes relevant. By means of simulation, we investigate the influence of
      variable percentages of ACC vehicles on traffic flow characteristics. For
      simulating the ACC vehicles, we propose a new car-following model that also
      serves as the basis of an ACC implementation in real cars. The model is based on
      the intelligent driver model (IDM) and inherits its intuitive behavioural
      parameters: desired velocity, acceleration, comfortable deceleration and desired
      minimum time headway. It eliminates, however, the sometimes unrealistic behaviour
      of the IDM in cut-in situations with ensuing small gaps that regularly are caused
      by lane changes of other vehicles in dense or congested traffic. We simulate the
      influence of different ACC strategies on the maximum capacity before breakdown
      and the (dynamic) bottleneck capacity after breakdown. With a suitable strategy,
      we find sensitivities of the order of 0.3, i.e. 1 per cent more ACC vehicles will
      lead to an increase in the capacities by about 0.3 per cent. This sensitivity
      multiplies when considering travel times at actual breakdowns.

PMID- 20819824
TI  - Active traffic management on road networks: a macroscopic approach.
AB  - Active traffic management (ATM) is the ability to dynamically manage recurrent
      and non-recurrent congestion based on prevailing traffic conditions in order to
      maximize the effectiveness and efficiency of road networks. It is a continuous
      process of (i) obtaining and analysing traffic measurement data, (ii) operations
      planning, i.e. simulating various scenarios and control strategies, (iii)
      implementing the most promising control strategies in the field, and (iv)
      maintaining a real-time decision support system that filters current traffic
      measurements to predict the traffic state in the near future, and to suggest the
      best available control strategy for the predicted situation. ATM relies on a fast
      and trusted traffic simulator for the rapid quantitative assessment of a large
      number of control strategies for the road network under various scenarios, in a
      matter of minutes. The open-source macrosimulation tool Aurora ROAD NETWORK
      MODELER is a good candidate for this purpose. The paper describes the underlying
      dynamical traffic model and what it takes to prepare the model for simulation;
      covers the traffic performance measures and evaluation of scenarios as part of
      operations planning; introduces the framework within which the control strategies
      are modelled and evaluated; and presents the algorithm for real-time traffic
      state estimation and short-term prediction.

PMID- 20819825
TI  - The spatial variability of vehicle densities as determinant of urban network
      capacity.
AB  - Due to the complexity of the traffic flow dynamics in urban road networks, most
      quantitative descriptions of city traffic so far have been based on computer
      simulations. This contribution pursues a macroscopic (fluid-dynamic) simulation
      approach, which facilitates a simple simulation of congestion spreading in
      cities. First, we show that a quantization of the macroscopic turning flows into
      units of single vehicles is necessary to obtain realistic fluctuations in the
      traffic variables, and how this can be implemented in a fluid-dynamic model.
      Then, we propose a new method to simulate destination flows without the
      requirement of individual route assignments. Combining both methods allows us to
      study a variety of different simulation scenarios. These reveal fundamental
      relationships between the average flow, the average density and the variability
      of the vehicle densities. Considering the inhomogeneity of traffic as an
      independent variable can eliminate the scattering of congested flow measurements.
      The variability also turns out to be a key variable of urban traffic performance.
      Our results can be explained through the number of full links of the road
      network, and approximated by a simple analytical formula.

PMID- 20819826
TI  - Autonomous driving in urban environments: approaches, lessons and challenges.
AB  - The development of autonomous vehicles for urban driving has seen rapid progress
      in the past 30 years. This paper provides a summary of the current state of the
      art in autonomous driving in urban environments, based primarily on the
      experiences of the authors in the 2007 DARPA Urban Challenge (DUC). The paper
      briefly summarizes the approaches that different teams used in the DUC, with the
      goal of describing some of the challenges that the teams faced in driving in
      urban environments. The paper also highlights the long-term research challenges
      that must be overcome in order to enable autonomous driving and points to
      opportunities for new technologies to be applied in improving vehicle safety,
      exploiting intelligent road infrastructure and enabling robotic vehicles
      operating in human environments.

PMID- 20819827
TI  - Monolateral purple urine bag syndrome in bilateral nephrostomy.

PMID- 20819828
TI  - Serum vascular endothelial growth factor (VEGF) levels correlate with number and
      location of micrometastases in a murine model of uveal melanoma.
AB  - BACKGROUND: A preliminary animal study was performed to determine if hepatic
      micrometastases from uveal melanoma secrete vascular endothelial growth factor
      (VEGF) that is measurable in serum. METHODS: We analysed the serum of a C57Bl/6
      mouse model of uveal melanoma (n=10) at days 4, 7, 14 and 21 post-inoculation for
      VEGF levels. We compared the serum VEGF levels with the number and location of
      hepatic micrometastases and their respective expression of VEGF mRNA. RESULTS:
      Serum VEGF levels rose after inoculation of C57Bl/6 mice eyes with B16LS9
      cutaneous melanoma cells. Beginning on day 14 there was a statistically
      significant (p<0.05) increase in VEGF levels, rising to an average peak level of
      37.985 pg/ml at day 21. Peak serum VEGF levels correlated with the total number
      of hepatic micrometastases (R=0.444) and there was moderate correlation of peak
      VEGF serum levels with micrometastases in more hypoxic locations (R=0.572). VEGF
      mRNA expression by micrometastases was highest in the most hypoxic regions of the
      hepatic lobule. CONCLUSIONS: Hepatic micrometastastic melanoma arising in a mouse
      model of ocular melanoma secretes VEGF. The number and location of the
      micrometastases correlate with serum VEGF levels.

PMID- 20819829
TI  - Coronary vein angioplasty to facilitate implantation of left ventricular lead.
AB  - AIMS: Stenosis in the coronary veins can cause the failure of left ventricular
      (LV) lead implantation, which is the cornerstone of cardiac resynchronization
      therapy (CRT). There are several cases in which LV pacing could be possible after
      successful elimination of coronary vein stenosis by coronary vein angioplasty.
      The study was conducted to investigate the efficacy of coronary vein angioplasty
      with an aim to a facilitate implantation of LV lead. METHODS AND RESULTS:
      Transvenous LV leads were implanted in 118 consecutive patients from November
      2001 to January 2009. Retrospective analysis performed by the CRT system showed
      that 3 of 118 patients (2.54%) needed coronary vein angioplasty to facilitate the
      lead placement. Each target vein was successfully dilated by using coronary
      balloon angioplasty catheters of 2.5 mm (2 patients) and 3.0 mm (1 patient). Then
      the LV leads could be inserted and there were no complications. CONCLUSION:
      Coronary vein angioplasty is an effective and safe technique to make transvenous
      LV pacing lead insertion a possibility in case of target vein stenoses.

PMID- 20819830
TI  - Applying the social cognitive perspective to volunteer intention in China: the
      mediating roles of self-efficacy and motivation.
AB  - When predicting volunteer intention, much attention is paid to the volunteer
      organization environment (VOE). Given that self-efficacy and motivation have
      emerged as important predictors of volunteer intention, we adopted a combination
      of ideas of Bandura's social cognitive theory and Ajzen's theory of planned
      behavior integrating VOE, self-efficacy and motivation to examine their effects
      on volunteer intention and to determine whether self-efficacy and motivation
      mediate the relationship between VOE and volunteer intention. The subjects of
      this study consisted of 198 community health volunteers in Shanghai city, China.
      Exploratory factor analysis was performed to identify the factor structure using
      standard principal component analysis. Six new factors were revealed, including
      two VOE factors, relation with organization and support from government; two
      motivation factors, personal attitude and social recognition; self-efficacy and
      volunteer intention. The results of a hierarchical regression analysis indicated
      that relation with organization accounted for 14.8% of the variance in volunteer
      intention, and support from government failed to add significantly to variance in
      volunteer intention; self-efficacy and personal attitude motivation partially
      mediated the effects of relation with organization on volunteer intention; social
      recognition motivation did not mediate the relationship between relation with
      organization and volunteer intention; and relation with organization, self
      efficacy and personal attitude motivation accounted for 33.7% of the variance in
      volunteer intention. These results provide support for self-efficacy and personal
      attitude motivation as mediators and provide preliminary insight into the
      potential mechanisms for predicting volunteer intention and improving
      volunteering by integrating VOE, self-efficacy and motivation factors.

PMID- 20819831
TI  - Individual patient data meta-analysis: a promising approach for evidence
      synthesis in reproductive medicine.
AB  - Systematic reviews and accompanying meta-analyses are the cornerstones of
      evidence-based medicine. Systematic reviews summarize clinical evidence; meta
      analyses provide summary estimates of the treatment effect or the diagnostic test
      accuracy. Although deemed to provide the highest level of evidence, their
      clinical value is limited as they can only summarize aggregated data. In these
      meta-analyses the true variability of the treatment effects cannot be explored to
      the desired extent, because the meta-analyses cannot distinguish between patients
      with different clinical profiles. Systematic reviews and meta-analyses based on
      individual patient data (IPD), described as the 'gold standard' for systematic
      reviews are a promising approach that might overcome these limitations. IPD meta
      analyses allow treatment effects and diagnostic accuracy to be estimated at the
      level of relevant patient subgroups. This enables researchers to investigate the
      effectiveness of treatment in patients with different profiles. In this article,
      we address the opportunities of systematic reviews and meta-analyses using IPD in
      reproductive medicine. We discuss its potential based on three clinical examples:
      single versus double embryo transfer in IVF, the diagnosis of tubal pathology and
      the prognostic value of ovarian reserve tests. We propose to show potential
      advantages of IPD systematic reviews and meta-analyses in providing stratified
      clinical evidence, which could improve medical care.

PMID- 20819832
TI  - A multicenter phase-II study of 5-FU, leucovorin and oxaliplatin (FOLFOX6) in
      patients with pretreated metastatic colorectal cancer.
AB  - OBJECTIVE: Infusional 5-fluorouracil and leucovorin with oxaliplatin is one of
      the standard regimens for patients with pretreated metastatic colorectal cancer,
      as well as for first-line chemotherapy. FOLFOX4 has shown its efficacy in pivotal
      trials, but patients must make twice-weekly hospital visits. FOLFOX6 is a more
      convenient regimen, requiring a visit once every two weeks. The objective of this
      study was to evaluate the efficacy and safety profile of FOLFOX6 in Japanese
      patients with pretreated colorectal cancer. METHOD: Fifty-one metastatic
      colorectal cancer patients who failed to respond to first-line chemotherapy were
      enrolled in the study from April to July 2005. Oxaliplatin, 5-fluorouracil and l
      leucovorin were administered every two weeks. Oxaliplatin (100 mg/m(2)) and l
      leucovorin (200 mg/m(2)) were given intravenously over 2 h followed by 5
      fluorouracil bolus 400 mg/m(2) i.v. and 46-h infusion of 2400 mg/m(2). The
      primary endpoint was the response rate. RESULTS: Two patients had no measurable
      lesions and were excluded from the efficacy analysis. Of the 49 eligible
      patients, one complete response and 6 partial responses were observed, resulting
      in a response rate (RR) of 14.3% (95% confidence interval: 5.9-27.2%). Median
      time to treatment failure and progression-free survival was 4.4 and 5.3 months,
      respectively. Overall survival was 11.4 months. The incidence of grade 2/3
      (Debiopharm neurotoxicity criteria) peripheral neuropathy was 41.2%, whereas the
      overall incidence of grade 3/4 neutropenia was 43.2%. CONCLUSION: The results of
      our study suggest that FOLFOX6 had an acceptable profile in terms of both
      efficacy and safety in previously treated colorectal cancer patients.

PMID- 20819833
TI  - Population-based survival of cancer patients diagnosed between 1993 and 1999 in
      Japan: a chronological and international comparative study.
AB  - OBJECTIVE: The purpose of the present study was to collect data from population
      based cancer registries and to calculate relative 5-year survival of cancer
      patients in Japan. We also sought to determine time trends and to compare the
      results with international studies. METHODS: We asked 11 population-based cancer
      registries to submit individual data for patients diagnosed from 1993 to 1999,
      together with data on outcome after 5 years. Although all these registries
      submitted data (491 772 cases), only six met the required standards for the
      quality of registration data and follow-up investigation. The relative 5-year
      survival calculated by pooling data from 151 061 cases from six registries was
      taken as the survival for cancer patients in Japan. RESULTS: Relative 5-year
      survival (1997-99) was 54.3% for all cancers (males: 50.0%, females: 59.8%).
      Survival figures for all sites changed slightly over the 7-year period, from
      53.2% for the first 4 years of the study (1993-96) to 54.3% for the last 3 years
      (1997-99), however, a major improvement was observed in several primary sites.
      Some overall survival was lower in Japan than in the USA, but similar to that in
      European countries. Specifically, survival for uterine cancer, prostate cancer,
      testis cancer, lymphoma and leukemia was much lower in Japan than in other
      countries. However, survival was better in Japan mainly for cancers of the
      esophagus, stomach, colon, liver and gallbladder. CONCLUSION: The study suggests
      an improvement in cancer survival in several primary sites in Japan, which is
      consistent with the development of treatments and early detection.

PMID- 20819834
TI  - Multicentre phase II study of XELOX with bevacizumab in late-stage elderly
      patients with unresectable advanced/recurrent colorectal cancer: an ASCA study.
AB  - We are conducting an open-label multicentre phase II study to evaluate the
      efficacy and safety of the combination therapy of XELOX and bevacizumab in late
      stage elderly patients with unresectable advanced/recurrent colorectal cancer.
      The primary endpoint of the study is progression-free survival. The secondary
      endpoints are the toxicity, overall response rate, time to treatment failure and
      overall survival. Thirty-five patients are required for the study.

PMID- 20819835
TI  - Pessimism predicts anxiety, depression and quality of life in female cancer
      patients.
AB  - OBJECTIVE: The aim of this study was to investigate the predictive value of
      optimism/pessimism for anxiety, depression and health-related quality of life in
      female cancer patients, quantified with and without controlling the corresponding
      base level. METHODS: A total of 97 women with breast cancer and other
      gynaecological cancer completed the Life Orientation Test, the Hospital Anxiety
      and Depression Scale and the Health Survey SF-8 at three time points: during
      their stay in the hospital (T1), 2 weeks later (T2) and 3 months later (T3).
      RESULTS: The degree of self-assessed pessimism at T1 was significantly associated
      with anxiety, depression and health-related quality of life at T3. After
      controlling for the base levels of anxiety, depression and health-related quality
      of life, only the predictive value of pessimism remained significant and
      substantial. CONCLUSIONS: Especially, women with a high level of pessimism are at
      risk for higher levels of anxiety and depression in addition to lowered health
      related quality of life in the course of the disease. The results indicate that
      it seems to be more important not to be pessimistic than to be optimistic.

PMID- 20819836
TI  - Cancer incidence and incidence rates in Japan in 2005: based on data from 12
      population-based cancer registries in the Monitoring of Cancer Incidence in Japan
      (MCIJ) project.
AB  - The Japan Cancer Surveillance Research Group estimated the cancer incidence in
      2005 as part of the Monitoring of Cancer Incidence in Japan (MCIJ) project, on
      the basis of data collected from 12 of 30 population-based cancer registries. The
      total number of incidences in Japan for 2005 was estimated as 646,802 (C00-C96).
      The leading cancer site was the stomach for men and the breast for women. Age
      standardized incidence rates remained almost the same level as the previous 2
      years.

PMID- 20819837
TI  - Usefulness of right ventricular myocardial strain in assessment of response to
      thrombolytic therapy in acute pulmonary embolism.
AB  - Acute pulmonary embolism (PE) is a life-threatening illness that is an important
      cause of morbidity and mortality. Patients with extensive emboli usually have
      associated right ventricular (RV) dysfunction. With anticoagulation therapy, RV
      function usually returns to normal. In patients with massive and submassive PE,
      echocardiography may directly visualize the embolus or more commonly provide
      evidence of its haemodynamic sequelae. The McConnell's sign involving sparing of
      RV apical contraction coupled with akinesia of the RV free wall has previously
      been reported in patients with acute PE. We present a case of a patient who had
      massive acute PE with severe RV systolic dysfunction that was demonstrated with
      both conventional Doppler and strain imaging. Strain imaging was also able to
      demonstrate the rapid improvement of RV function in response to thrombolytic
      therapy.

PMID- 20819838
TI  - Coronary flow reserve assessed by myocardial contrast echocardiography predicts
      mortality in patients with heart failure.
AB  - AIMS: the aim of the study was to assess whether myocardial contrast
      echocardiography (MCE) can predict mortality in patients with heart failure.
      Myocardial viability, ischaemia, and coronary flow reserve (CFR) are predictors
      of mortality in patients with heart failure. MCE can assess myocardial viability,
      ischaemia, and CFR at the bedside. However, its prognostic value is unknown in
      patients with heart failure. METHODS AND RESULTS: eighty-seven patients (age: 68
      +/- 10 years, 62% male) with heart failure [left ventricular ejection fraction
      (LVEF): 35% +/- 13] underwent low-power intermittent MCE at rest and 2 min after
      dipyridamole infusion. Resting and stress perfusion score index were derived
      qualitatively. CFR (MBF at stress/MBF at rest) was calculated by a quantitative
      method. All patients underwent coronary arteriography. Patients were followed up
      for mortality. Of the 87 patients, 43 (49%) patients had coronary artery disease.
      There were 28 (32%) deaths during a mean follow-up of 4.1 +/- 1.7 years. Type 2
      diabetes [P = 0.02, hazard ratios (HR) 2.43, confidence interval (CI) 1.13-5.22]
      and CFR (P = 0.001, HR 0.15, CI 0.05-0.45) were independent predictors of
      mortality. A CFR <= 1.5 had a significantly (P < 0.0001) higher mortality of 49
      vs. 10% in patients with CFR > 1.5 over the 4 year follow-up period. CONCLUSION:
      CFR determined by MCE is a powerful predictor of mortality in patients with heart
      failure.

PMID- 20819839
TI  - Illustration of the echocardiographic diagnosis of subaortic membrane stenosis in
      adults: surgical and live three-dimensional transoesophageal findings.
AB  - We report here two cases of patients admitted in our institution for heart
      failure. The first had been previously diagnosed with severe aortic valve
      stenosis and was referred for aortic valve replacement. The myocardial and
      valvular anatomy combined with the Doppler profiles allowed, however, to suggest
      the diagnosis of a discrete subaortic membrane that was confirmed by surgical
      findings. In the second case, the use of real-time three-dimensional
      transoesophageal echocardiography (3D TEE) provided superb 3D visualization
      quality of the subaortic membrane and allowed assessing the stenosis area using
      the multiplanar review mode. Hence, the use of live real-time 3D TEE is likely to
      be key in the spatial assessment of this complex lesion.

PMID- 20819840
TI  - Measurement error in the timing of events: effect on survival analyses in
      randomized clinical trials.
AB  - BACKGROUND: Presence of measurement error in the outcome can complicate the
      interpretation of a randomized clinical trial. The Oncologic Drugs Advisory
      Committee of the US Food and Drug Administration voted against recommending
      approval of bevacizumab for the initial treatment of metastatic breast cancer;
      one of their major concerns was the presence of a large amount of nondifferential
      measurement error in the evaluation of progression-free survival, the primary
      outcome of the randomized clinical trial E2100. PURPOSE: To investigate the
      effects of nondifferential measurement error in time-to-event outcomes on the
      conclusions of a proportional hazards analysis of a randomized clinical trial.
      METHODS: Simulations were performed showing effects of measurement error on the
      estimated treatment effect (hazard ratio) in a clinical trial. In some
      simulations, the measurement error structure from E2100 data was approximated;
      for other simulations, larger or smaller measurement error was considered.
      RESULTS: The bias in estimating the hazard ratio was very small using measurement
      error and a hazard ratio similar to E2100. Even with a larger nondifferential
      measurement error, the bias remained small when the hazard ratio was in a range
      commonly seen in clinical trials. There was no or little effect on the
      variability of the estimated treatment effect. LIMITATIONS: Because of censoring
      issues, retrospective evaluation of the measurement error structure from a
      completed trial is difficult. Although our simulations cover a range of plausible
      measurement error values, in theory, a trial could have much larger measurement
      error than we considered. Differential measurement error is only briefly
      considered. CONCLUSIONS: Nondifferential measurement error due to variability in
      estimating time-to-event outcomes will typically not be a major concern in
      randomized clinical trials.

PMID- 20819841
TI  - Adaptive dose insertion in early phase clinical trials.
AB  - BACKGROUND AND PURPOSE: We propose to adaptively insert new doses during the
      course of a dose-finding trial when none of the prespecified doses in the trial
      are acceptable, for example, have tolerable toxicity. METHODS: Our procedure uses
      an activation rule to determine whether a new dose is needed and an inverse dose
      response algorithm to estimate new doses to be inserted into the trial. RESULTS:
      The proposed method can be applied to both one-agent and two-agent trials. In
      application to a Phase I trial about advanced ovarian cancer, our method selected
      a new dose that is better than all prespecified doses in at least 44%
      simulations. The effectiveness of the procedure was also demonstrated in a
      simulation study. LIMITATIONS: The proposed method is applicable to dose-finding
      trials with binary responses. CONCLUSIONS: We believe that with the added
      adaptive dose insertion, traditional dose-finding trials will have better chances
      of locating desirable doses. In addition, by allowing for dose insertion,
      unnecessary trial suspension due to lack of acceptable doses can be avoided.

PMID- 20819842
TI  - Validation of the Headache Impact Test (HIT-6TM) across episodic and chronic
      migraine.
AB  - OBJECTIVE: The purpose of this study was to assess psychometric properties of the
      six-item Headache Impact Text (HIT-6TM) across episodic and chronic migraine.
      METHODS: Using a migraine screener and number of headache days per month (HDPM),
      participants from the National Survey of Headache Impact (NSHI) study and the HIT
      6 validation study (HIT6-V) were selected for this study. Eligible participants
      were categorized into three groups: chronic migraine (CM: >= 15 HDPM); episodic
      migraine (EM: < 15 HDPM); non-migraine headaches. Reliability and validity of the
      HIT-6 were evaluated. RESULTS: A total of 2,049 survey participants met the
      inclusion/exclusion criteria for this study. Participants were identified as 6.4%
      CM; 42.1% EM; 51.5% non-migraine, with respective mean HIT-6 scores: 62.5 +/-
      7.8; 60.2 +/- 6.8; and 49.1 +/- 8.7. High reliability was demonstrated with
      internal consistency (time1/time2) of 0.83/0.87 in NSHI, and 0.82/0.92 in HIT6-V.
      Intra-class correlation for test-retest reliability was very good at 0.77. HIT-6
      scores correlated significantly (p < .0001) with total Migraine Disability
      Assessment Scale scores (r = 0.56), headache pain severity (r = 0.46), and HDPM
      (r = 0.29). Discriminant validity analysis showed significantly different HIT-6
      scores (F = 488.02, p < .0001) across the groups. CONCLUSION: Results from these
      analyses confirm that the HIT-6 is a reliable and valid tool for discriminating
      headache impact across episodic and chronic migraine.

PMID- 20819843
TI  - One-year prevalence of migraine in Spain: a nationwide population-based survey.
AB  - AIM: The purpose of the study was to estimate the one-year prevalence of migraine
      among a population-based sample of Spanish adults. METHOD: Men and women aged 18
      65 years were selected at random according to quotas for age, sex, size of
      habitat (<10,000 inhabitants, 10,001-50,000 inhabitants, 50,001-200,000
      inhabitants and >200,000 inhabitants) and residence proportional to the
      population size of the geographical location. A random-digit-dial, computer
      assisted telephone interview (CATI) survey was conducted between April and July
      2006. The 2004 International Headache Society operational diagnostic criteria
      were applied. RESULTS: From a total of 70,692 telephone calls and 26,255 (31.7%)
      valid contacts, 5,668 (21.6%) respondents completed the CATI survey. A total of
      476 subjects (8.4%, 95% confidence interval [CI] 7.7-9.1%) with strict migraine
      and 236 with probable migraine (4.2%, 95% CI 3.7-4.7%) were recorded. The 1-year
      prevalence of total migraine (N = 712) was 12.6% (95% CI 11.6-13.6) (17.2% in
      females, 8.0% in males). The prevalence rates showed significant geographic
      variations, from 7.6% in Navarra to 18% in the Canary Islands. One-half of the
      subjects had migraine with aura. One-third of subjects were never diagnosed for
      migraine. CONCLUSIONS: The one-year prevalence of migraine in Spain is 12.6%,
      with a prevalence of migraine with and without aura of 8.4% and probable migraine
      of 4.2%. These findings add data to the current understanding of migraine.

PMID- 20819844
TI  - Orthostatic and non-orthostatic headache in postural tachycardia syndrome.
AB  - OBJECTIVE: Orthostatic and non-orthostatic headache spectrum was prospectively
      studied in 24 consecutive patients with postural orthostatic tachycardia syndrome
      (POTS). METHODS: Patients were interviewed about clinical aspects of headache and
      its precipitation during head-up tilt (HUT). Autonomic functions were assessed
      using a standard battery of tests. The relationship of orthostatic headache to
      cardiovascular variables was examined using unpaired two-tailed t-test. RESULTS:
      Orthostatic headache occurred during daily activity in 14 patients (58.3%) and
      during HUT in 15 patients (62.5%). Age under 30 years and increasing duration of
      tilt were predictive for orthostatic headache. Of the 24 patients, 23 (95.8%) had
      non-orthostatic headache fitting the criteria of migraine or probable migraine.
      CONCLUSIONS: Orthostatic headache affected two-thirds of POTS patients,
      especially those under age 30. Patients with orthostatic headache should be
      clinically assessed for POTS and informed of this association to reduce short
      term morbidity. Migraine afflicted almost all POTS patients. This co-morbidity
      should be considered in management of POTS.

PMID- 20819845
TI  - Activation of MAP kinases during progression of radiation-induced pneumonitis in
      rats.
AB  - Radiation-induced pneumonitis is closely associated with the interplay of various
      stress-activated signals and immune responses related to the progression of lung
      injury. Mitogen-activated protein (MAP) kinase pathways play critical roles in
      the progression of inflammation via a cellular damage. Here, we examined the
      regional distribution of phosphorylated MAP kinases (p-JNK, p-ERK, and p-p38) in
      the progression of pneumonitis after exposure of a single dose irradiation with
      10 Gy for 0, 4, and 8 weeks in rats. Also, we identified positive cells for these
      kinases using specific cell-type markers related to inflammation and type II
      pneumocyte. p-JNK was present abundantly in activated macrophages, CD8(+)T-cells,
      peribronchiolar smooth muscle cells, and weakly type II pneumocytes at 4 weeks or
      8 weeks after irradiation. p-p38 and p-ERK was predominantly expressed in
      macrophages, CD4(+) T-cells, fibrotic cells as well as present in various lung
      parenchymal cells including alveolar epithelial cells and type II pneumocytes. In
      conclusion, it is considered that MAP kinase pathways play a pivotal role in
      early damage of residual cells as well as in the long-term regulation of distinct
      inflammatory cells during the progression of radiation-induced pneumonitis.

PMID- 20819846
TI  - End-of-life practices in palliative care: a cross sectional survey of physician
      members of the German Society for Palliative Medicine.
AB  - OBJECTIVES: To elicit types and frequencies of end-of-life practices by physician
      members of the German Society for Palliative Medicine. To analyse associations
      between characteristics of physicians and patients and end-of-life practices with
      intended hastening of death. DESIGN: Cross-sectional postal survey. MAIN OUTCOME
      MEASURES: Types and frequencies of end-of-life practices with foreseeable or
      intended hastening of patients' death. Association between end-of-life practices
      with hastening of death and predefined characteristics of physicians and
      patients. RESULTS: Nine hundred and one physicians participated in the study
      (response rate: 55.8%). There was alleviation of symptoms in 78.1% and limitation
      of medical treatment with possible life shortening in 69.1% of cases. In 10 cases
      medication had been administered by the physician (N = 9) or the patient (N = 1)
      with the intention to hasten death. Patients' best interest and avoidance of
      possible harm to the patient were reported as reasons for non-involvement of
      competent patients in decision making. Physicians with added qualification in
      palliative medicine significantly less frequently reported end-of-life practices
      with intended hastening of death (p = 0.003). CONCLUSION: Physician members of
      the German Society for Palliative Medicine perform a broad spectrum of end-of
      life practices including intended hastening of death. The findings on patients'
      non-involvement in decision making warrant further empirical-ethical analysis.

PMID- 20819847
TI  - Analysing the production and treatment of solid waste using a national accounting
      framework.
AB  - Our knowledge of the relationship between the economy and the environment has
      increased significantly over recent decades. One of the areas in which this is
      most apparent is the area of environmental accounting, where environmental data
      is presented according to national accounting principles. These accounts provide
      consistent, complete and detailed information for understanding environmental
      economic interdependencies. One of the modules of these accounts is the waste
      accounts which record the origin and destination of waste materials. The first
      part of this paper discusses the Dutch waste accounts and their relation with
      economic indicators. In the second part a number of applications, which are based
      on the input-output model, are applied to these accounts. This section includes a
      novel structural decomposition analysis which quantifies the underlying driving
      forces of changes in total waste and landfilled waste between 1995 and 2004. The
      results show that the total amount of waste is mainly driven by economic growth
      (positive effect) and the direct export of waste (negative effect). The models
      also show that the construction sector has played a very important part in the
      reduction of waste. Furthermore, the decrease in the amount of landfilled waste,
      which is caused by Dutch regulations, has led to a large shift towards recycling
      and to a lesser degree incineration. Finally, the calculations for the
      'environmental trade balance' for waste show that the waste-contents of exports
      exceed that of imports. This paper shows that the waste accounts have many
      analytical and policy-relevant applications.

PMID- 20819848
TI  - Transmissivity evolution through interface of composite liners under applied
      constraint.
AB  - In landfill liners, geomembranes have defects that constitute preferential
      passages of leachate from rainwater percolation. Non-woven geotextiles are widely
      used in wastelandfills as materials having the functions of protection,
      separation, filtration and drainage. This study seeks to select geotextiles
      through an investigation conducted among landfill operators who commonly arise a
      geotextile in the geomembrane-clay interface to facilitate geomembrane welding
      and to prevent its puncture by angular materials. It also attempts to find out
      the influence of geotextile in a decimetric transmissivity cell size under 50 kPa
      stress and smooth ground surface. The results show that the transmissivity in
      composite liner interface is almost the same as the one calculated with the
      European standard EN ISO 12958. Transmissivity depends on the mechanical stress
      applied to the bottom liner, on the geotextile type in the interface and on the
      ground surface.

PMID- 20819850
TI  - Clinical decision support: progress and opportunities.
AB  - In 2005, the American Medical Informatics Association undertook a set of
      activities relating to clinical decision support (CDS), with support from the
      office of the national coordinator and the Agency for Healthcare Research and
      Quality. They culminated in the release of the roadmap for national action on CDS
      in 2006. This article assesses progress toward the short-term goals within the
      roadmap, and recommends activities to continue to improve CDS adoption throughout
      the United States. The report finds that considerable progress has been made in
      the past four years, although significant work remains. Healthcare quality
      organizations are increasingly recognizing the role of health information
      technology in improving care, multi-site CDS demonstration projects are under
      way, and there are growing incentives for adoption. Specific recommendations
      include: (1) designating a national entity to coordinate CDS work and
      collaboration; (2) developing approaches to monitor and track CDS adoption and
      use; (3) defining and funding a CDS research agenda; and (4) updating the CDS
      'critical path'.

PMID- 20819849
TI  - The p.M292T NDUFS2 mutation causes complex I-deficient Leigh syndrome in multiple
      families.
AB  - Isolated complex I deficiency is the most frequently observed oxidative
      phosphorylation defect in children with mitochondrial disease, leading to a
      diverse range of clinical presentations, including Leigh syndrome. For most
      patients the genetic cause of the biochemical defect remains unknown due to
      incomplete understanding of the complex I assembly process. Nonetheless, a
      plethora of pathogenic mutations have been described to date in the seven
      mitochondrial-encoded subunits of complex I as well as in 12 of the nuclear
      encoded subunits and in six assembly factors. Whilst several mitochondrial DNA
      mutations are recurrent, the majority of these mutations are reported in single
      families. We have sequenced core structural and functional nuclear-encoded
      subunits of complex I in a cohort of 34 paediatric patients with isolated complex
      I deficiency, identifying pathogenic mutations in 6 patients. These included a
      novel homozygous NDUFS1 mutation in an Asian child with Leigh syndrome, a
      previously identified NDUFS8 mutation (c.236C>T, p.P79L) in a second Asian child
      with Leigh-like syndrome and six novel, compound heterozygous NDUFS2 mutations in
      four white Caucasian patients with Leigh or Leigh-like syndrome. Three of these
      children harboured an identical NDUFS2 mutation (c.875T>C, p.M292T), which was
      also identified in conjunction with a novel NDUFS2 splice site mutation
      (c.866+4A>G) in a fourth Caucasian child who presented to a different diagnostic
      centre, with microsatellite and single nucleotide polymorphism analyses
      indicating that this was due to an ancient common founder event. Our results
      confirm that NDUFS2 is a mutational hotspot in Caucasian children with isolated
      complex I deficiency and recommend the routine diagnostic investigation of this
      gene in patients with Leigh or Leigh-like phenotypes.

PMID- 20819851
TI  - A review of human factors principles for the design and implementation of
      medication safety alerts in clinical information systems.
AB  - The objective of this review is to describe the implementation of human factors
      principles for the design of alerts in clinical information systems. First, we
      conduct a review of alarm systems to identify human factors principles that are
      employed in the design and implementation of alerts. Second, we review the
      medical informatics literature to provide examples of the implementation of human
      factors principles in current clinical information systems using alerts to
      provide medication decision support. Last, we suggest actionable recommendations
      for delivering effective clinical decision support using alerts. A review of
      studies from the medical informatics literature suggests that many basic human
      factors principles are not followed, possibly contributing to the lack of
      acceptance of alerts in clinical information systems. We evaluate the limitations
      of current alerting philosophies and provide recommendations for improving
      acceptance of alerts by incorporating human factors principles in their design.

PMID- 20819852
TI  - Implementing practice-linked pre-visit electronic journals in primary care:
      patient and physician use and satisfaction.
AB  - Electronic health records (EHRs) and EHR-connected patient portals offer patient
      provider collaboration tools for visit-based care. During a randomized controlled
      trial, primary care patients completed pre-visit electronic journals (eJournals)
      containing EHR-based medication, allergies, and diabetes (study arm 1) or health
      maintenance, personal history, and family history (study arm 2) topics to share
      with their provider. Assessment with surveys and usage data showed that among
      2027 patients invited to complete an eJournal, 70.3% submitted one and 71.1% of
      submitters had one opened by their provider. Surveyed patients reported they felt
      more prepared for the visit (55.9%) and their provider had more accurate
      information about them (58.0%). More arm 1 versus arm 2 providers reported that
      eJournals were visit-time neutral (100% vs 53%; p<0.013), helpful to patients in
      visit preparation (66% vs 20%; p=0.082), and would recommend them to colleagues
      (78% vs 22%; p=0.0143). eJournal integration into practice warrants further
      study.

PMID- 20819853
TI  - Mayo clinical Text Analysis and Knowledge Extraction System (cTAKES):
      architecture, component evaluation and applications.
AB  - We aim to build and evaluate an open-source natural language processing system
      for information extraction from electronic medical record clinical free-text. We
      describe and evaluate our system, the clinical Text Analysis and Knowledge
      Extraction System (cTAKES), released open-source at http://www.ohnlp.org. The
      cTAKES builds on existing open-source technologies-the Unstructured Information
      Management Architecture framework and OpenNLP natural language processing
      toolkit. Its components, specifically trained for the clinical domain, create
      rich linguistic and semantic annotations. Performance of individual components:
      sentence boundary detector accuracy=0.949; tokenizer accuracy=0.949; part-of
      speech tagger accuracy=0.936; shallow parser F-score=0.924; named entity
      recognizer and system-level evaluation F-score=0.715 for exact and 0.824 for
      overlapping spans, and accuracy for concept mapping, negation, and status
      attributes for exact and overlapping spans of 0.957, 0.943, 0.859, and 0.580,
      0.939, and 0.839, respectively. Overall performance is discussed against five
      applications. The cTAKES annotations are the foundation for methods and modules
      for higher-level semantic processing of clinical free-text.

PMID- 20819854
TI  - Extracting medication information from clinical text.
AB  - The Third i2b2 Workshop on Natural Language Processing Challenges for Clinical
      Records focused on the identification of medications, their dosages, modes
      (routes) of administration, frequencies, durations, and reasons for
      administration in discharge summaries. This challenge is referred to as the
      medication challenge. For the medication challenge, i2b2 released detailed
      annotation guidelines along with a set of annotated discharge summaries. Twenty
      teams representing 23 organizations and nine countries participated in the
      medication challenge. The teams produced rule-based, machine learning, and hybrid
      systems targeted to the task. Although rule-based systems dominated the top 10,
      the best performing system was a hybrid. Of all medication-related fields,
      durations and reasons were the most difficult for all systems to detect. While
      medications themselves were identified with better than 0.75 F-measure by all of
      the top 10 systems, the best F-measure for durations and reasons were 0.525 and
      0.459, respectively. State-of-the-art natural language processing systems go a
      long way toward extracting medication names, dosages, modes, and frequencies.
      However, they are limited in recognizing duration and reason fields and would
      benefit from future research.

PMID- 20819855
TI  - Community annotation experiment for ground truth generation for the i2b2
      medication challenge.
AB  - OBJECTIVE: Within the context of the Third i2b2 Workshop on Natural Language
      Processing Challenges for Clinical Records, the authors (also referred to as 'the
      i2b2 medication challenge team' or 'the i2b2 team' for short) organized a
      community annotation experiment. DESIGN: For this experiment, the authors
      released annotation guidelines and a small set of annotated discharge summaries.
      They asked the participants of the Third i2b2 Workshop to annotate 10 discharge
      summaries per person; each discharge summary was annotated by two annotators from
      two different teams, and a third annotator from a third team resolved
      disagreements. MEASUREMENTS: In order to evaluate the reliability of the
      annotations thus produced, the authors measured community inter-annotator
      agreement and compared it with the inter-annotator agreement of expert annotators
      when both the community and the expert annotators generated ground truth based on
      pooled system outputs. For this purpose, the pool consisted of the three most
      densely populated automatic annotations of each record. The authors also compared
      the community inter-annotator agreement with expert inter-annotator agreement
      when the experts annotated raw records without using the pool. Finally, they
      measured the quality of the community ground truth by comparing it with the
      expert ground truth. RESULTS AND CONCLUSIONS: The authors found that the
      community annotators achieved comparable inter-annotator agreement to expert
      annotators, regardless of whether the experts annotated from the pool.
      Furthermore, the ground truth generated by the community obtained F-measures
      above 0.90 against the ground truth of the experts, indicating the value of the
      community as a source of high-quality ground truth even on intricate and domain
      specific annotation tasks.

PMID- 20819856
TI  - High accuracy information extraction of medication information from clinical
      notes: 2009 i2b2 medication extraction challenge.
AB  - OBJECTIVE: Medication information comprises a most valuable source of data in
      clinical records. This paper describes use of a cascade of machine learners that
      automatically extract medication information from clinical records. DESIGN:
      Authors developed a novel supervised learning model that incorporates two machine
      learning algorithms and several rule-based engines. MEASUREMENTS: Evaluation of
      each step included precision, recall and F-measure metrics. The final outputs of
      the system were scored using the i2b2 workshop evaluation metrics, including
      strict and relaxed matching with a gold standard. RESULTS: Evaluation results
      showed greater than 90% accuracy on five out of seven entities in the name entity
      recognition task, and an F-measure greater than 95% on the relationship
      classification task. The strict micro averaged F-measure for the system output
      achieved best submitted performance of the competition, at 85.65%. LIMITATIONS:
      Clinical staff will only use practical processing systems if they have confidence
      in their reliability. Authors estimate that an acceptable accuracy for a such a
      working system should be approximately 95%. This leaves a significant performance
      gap of 5 to 10% from the current processing capabilities. CONCLUSION: A
      multistage method with mixed computational strategies using a combination of rule
      based classifiers and statistical classifiers seems to provide a near-optimal
      strategy for automated extraction of medication information from clinical
      records.

PMID- 20819857
TI  - Integrating existing natural language processing tools for medication extraction
      from discharge summaries.
AB  - OBJECTIVE: To develop an automated system to extract medications and related
      information from discharge summaries as part of the 2009 i2b2 natural language
      processing (NLP) challenge. This task required accurate recognition of medication
      name, dosage, mode, frequency, duration, and reason for drug administration.
      DESIGN: We developed an integrated system using several existing NLP components
      developed at Vanderbilt University Medical Center, which included MedEx (to
      extract medication information), SecTag (a section identification system for
      clinical notes), a sentence splitter, and a spell checker for drug names. Our
      goal was to achieve good performance with minimal to no specific training for
      this document corpus; thus, evaluating the portability of those NLP tools beyond
      their home institution. The integrated system was developed using 17 notes that
      were annotated by the organizers and evaluated using 251 notes that were
      annotated by participating teams. MEASUREMENTS: The i2b2 challenge used standard
      measures, including precision, recall, and F-measure, to evaluate the performance
      of participating systems. There were two ways to determine whether an extracted
      textual finding is correct or not: exact matching or inexact matching. The
      overall performance for all six types of medication-related findings across 251
      annotated notes was considered as the primary metric in the challenge. RESULTS:
      Our system achieved an overall F-measure of 0.821 for exact matching (0.839
      precision; 0.803 recall) and 0.822 for inexact matching (0.866 precision; 0.782
      recall). The system ranked second out of 20 participating teams on overall
      performance at extracting medications and related information. CONCLUSIONS: The
      results show that the existing MedEx system, together with other NLP components,
      can extract medication information in clinical text from institutions other than
      the site of algorithm development with reasonable performance.

PMID- 20819858
TI  - Medication information extraction with linguistic pattern matching and semantic
      rules.
AB  - OBJECTIVE: This study presents a system developed for the 2009 i2b2 Challenge in
      Natural Language Processing for Clinical Data, whose aim was to automatically
      extract certain information about medications used by a patient from his/her
      medical report. The aim was to extract the following information for each
      medication: name, dosage, mode/route, frequency, duration and reason. DESIGN: The
      system implements a rule-based methodology, which exploits typical morphological,
      lexical, syntactic and semantic features of the targeted information. These
      features were acquired from the training dataset and public resources such as the
      UMLS and relevant web pages. Information extracted by pattern matching was
      combined together using context-sensitive heuristic rules. MEASUREMENTS: The
      system was applied to a set of 547 previously unseen discharge summaries, and the
      extracted information was evaluated against a manually prepared gold standard
      consisting of 251 documents. The overall ranking of the participating teams was
      obtained using the micro-averaged F-measure as the primary evaluation metric.
      RESULTS: The implemented method achieved the micro-averaged F-measure of 81%
      (with 86% precision and 77% recall), which ranked this system third in the
      challenge. The significance tests revealed the system's performance to be not
      significantly different from that of the second ranked system. Relative to other
      systems, this system achieved the best F-measure for the extraction of duration
      (53%) and reason (46%). CONCLUSION: Based on the F-measure, the performance
      achieved (81%) was in line with the initial agreement between human annotators
      (82%), indicating that such a system may greatly facilitate the process of
      extracting relevant information from medical records by providing a solid basis
      for a manual review process.

PMID- 20819859
TI  - Extracting Rx information from clinical narrative.
AB  - OBJECTIVE: The authors used the i2b2 Medication Extraction Challenge to evaluate
      their entity extraction methods, contribute to the generation of a publicly
      available collection of annotated clinical notes, and start developing methods
      for ontology-based reasoning using structured information generated from the
      unstructured clinical narrative. DESIGN: Extraction of salient features of
      medication orders from the text of de-identified hospital discharge summaries was
      addressed with a knowledge-based approach using simple rules and lookup lists.
      The entity recognition tool, MetaMap, was combined with dose, frequency, and
      duration modules specifically developed for the Challenge as well as a prototype
      module for reason identification. MEASUREMENTS: Evaluation metrics and
      corresponding results were provided by the Challenge organizers. RESULTS: The
      results indicate that robust rule-based tools achieve satisfactory results in
      extraction of simple elements of medication orders, but more sophisticated
      methods are needed for identification of reasons for the orders and durations.
      LIMITATIONS: Owing to the time constraints and nature of the Challenge, some
      obvious follow-on analysis has not been completed yet. CONCLUSIONS: The authors
      plan to integrate the new modules with MetaMap to enhance its accuracy. This
      integration effort will provide guidance in retargeting existing tools for better
      processing of clinical text.

PMID- 20819860
TI  - Improving textual medication extraction using combined conditional random fields
      and rule-based systems.
AB  - OBJECTIVE: In the i2b2 Medication Extraction Challenge, medication names together
      with details of their administration were to be extracted from medical discharge
      summaries. DESIGN: The task of the challenge was decomposed into three pipelined
      components: named entity identification, context-aware filtering and relation
      extraction. For named entity identification, first a rule-based (RB) method that
      was used in our overall fifth place-ranked solution at the challenge was
      investigated. Second, a conditional random fields (CRF) approach is presented for
      named entity identification (NEI) developed after the completion of the
      challenge. The CRF models are trained on the 17 ground truth documents, the
      output of the rule-based NEI component on all documents, a larger but potentially
      inaccurate training dataset. For both NEI approaches their effect on relation
      extraction performance was investigated. The filtering and relation extraction
      components are both rule-based. MEASUREMENTS: In addition to the official entry
      level evaluation of the challenge, entity level analysis is also provided.
      RESULTS: On the test data an entry level F(1)-score of 80% was achieved for exact
      matching and 81% for inexact matching with the RB-NEI component. The CRF produces
      a significantly weaker result, but CRF outperforms the rule-based model with 81%
      exact and 82% inexact F(1)-score (p<0.02). CONCLUSION: This study shows that a
      simple rule-based method is on a par with more complicated machine learners; CRF
      models can benefit from the addition of the potentially inaccurate training data,
      when only very few training documents are available. Such training data could be
      generated using the outputs of rule-based methods.

PMID- 20819861
TI  - Automatic extraction of medication information from medical discharge summaries.
AB  - OBJECTIVE: This article describes a system developed for the 2009 i2b2 Medication
      Extraction Challenge. The purpose of this challenge is to extract medication
      information from hospital discharge summaries. DESIGN: The system explored
      several linguistic natural language processing techniques (eg, term-based and
      token-based rule matching) to identify medication-related information in the
      narrative text. A number of lexical resources was constructed to profile lexical
      or morphological features for different categories of medication constituents.
      MEASUREMENTS: Performance was evaluated in terms of the micro-averaged F-measure
      at the horizontal system level. RESULTS: The automated system performed well, and
      achieved an F-micro of 80% for the term-level results and 81% for the token-level
      results, placing it sixth in exact matches and fourth in inexact matches in the
      i2b2 competition. CONCLUSION: The overall results show that this relatively
      simple rule-based approach is capable of tackling multiple entity identification
      tasks such as medication extraction under situations in which few training
      documents are annotated for machine learning approaches, and the entity
      information can be characterized with a set of feature tokens.

PMID- 20819862
TI  - Linguistic approach for identification of medication names and related
      information in clinical narratives.
AB  - BACKGROUND: Pharmacotherapy is an integral part of any medical care process and
      plays an important role in the medical history of most patients. Information on
      medication is crucial for several tasks such as pharmacovigilance, medical
      decision or biomedical research. OBJECTIVES: Within a narrative text, medication
      related information can be buried within other non-relevant data. Specific
      methods, such as those provided by text mining, must be designed for accessing
      them, and this is the objective of this study. METHODS: The authors designed a
      system for analyzing narrative clinical documents to extract from them medication
      occurrences and medication-related information. The system also attempts to
      deduce medications not covered by the dictionaries used. RESULTS: Results
      provided by the system were evaluated within the framework of the I2B2 NLP
      challenge held in 2009. The system achieved an F-measure of 0.78 and ranked 7th
      out of 20 participating teams (the highest F-measure was 0.86). The system
      provided good results for the annotation and extraction of medication names,
      their frequency, dosage and mode of administration (F-measure over 0.81), while
      information on duration and reasons is poorly annotated and extracted (F-measure
      0.36 and 0.29, respectively). The performance of the system was stable between
      the training and test sets.

PMID- 20819863
TI  - Extracting medical information from narrative patient records: the case of
      medication-related information.
AB  - OBJECTIVE: While essential for patient care, information related to medication is
      often written as free text in clinical records and, therefore, difficult to use
      in computerized systems. This paper describes an approach to automatically
      extract medication information from clinical records, which was developed to
      participate in the i2b2 2009 challenge, as well as different strategies to
      improve the extraction. DESIGN: Our approach relies on a semantic lexicon and
      extraction rules as a two-phase strategy: first, drug names are recognized and,
      then, the context of these names is explored to extract drug-related information
      (mode, dosage, etc) according to rules capturing the document structure and the
      syntax of each kind of information. Different configurations are tested to
      improve this baseline system along several dimensions, particularly drug name
      recognition-this step being a determining factor to extract drug-related
      information. Changes were tested at the level of the lexicons and of the
      extraction rules. RESULTS: The initial system participating in i2b2 achieved good
      results (global F-measure of 77%). Further testing of different configurations
      substantially improved the system (global F-measure of 81%), performing well for
      all types of information (eg, 84% for drug names and 88% for modes), except for
      durations and reasons, which remain problematic. CONCLUSION: This study
      demonstrates that a simple rule-based system can achieve good performance on the
      medication extraction task. We also showed that controlled modifications (lexicon
      filtering and rule refinement) were the improvements that best raised the
      performance.

PMID- 20819864
TI  - Textractor: a hybrid system for medications and reason for their prescription
      extraction from clinical text documents.
AB  - OBJECTIVE To describe a new medication information extraction system-Textractor
      developed for the 'i2b2 medication extraction challenge'. The development,
      functionalities, and official evaluation of the system are detailed. DESIGN:
      Textractor is based on the Apache Unstructured Information Management
      Architecture (UMIA) framework, and uses methods that are a hybrid between machine
      learning and pattern matching. Two modules in the system are based on machine
      learning algorithms, while other modules use regular expressions, rules, and
      dictionaries, and one module embeds MetaMap Transfer. MEASUREMENTS: The official
      evaluation was based on a reference standard of 251 discharge summaries annotated
      by all teams participating in the challenge. The metrics used were recall,
      precision, and the F(1)-measure. They were calculated with exact and inexact
      matches, and were averaged at the level of systems and documents. RESULTS: The
      reference metric for this challenge, the system-level overall F(1)-measure,
      reached about 77% for exact matches, with a recall of 72% and a precision of 83%.
      Performance was the best with route information (F(1)-measure about 86%), and was
      good for dosage and frequency information, with F(1)-measures of about 82-85%.
      Results were not as good for durations, with F(1)-measures of 36-39%, and for
      reasons, with F(1)-measures of 24-27%. CONCLUSION: The official evaluation of
      Textractor for the i2b2 medication extraction challenge demonstrated satisfactory
      performance. This system was among the 10 best performing systems in this
      challenge.

PMID- 20819865
TI  - Lancet: a high precision medication event extraction system for clinical text.
AB  - OBJECTIVE: This paper presents Lancet, a supervised machine-learning system that
      automatically extracts medication events consisting of medication names and
      information pertaining to their prescribed use (dosage, mode, frequency, duration
      and reason) from lists or narrative text in medical discharge summaries. DESIGN:
      Lancet incorporates three supervised machine-learning models: a conditional
      random fields model for tagging individual medication names and associated
      fields, an AdaBoost model with decision stump algorithm for determining which
      medication names and fields belong to a single medication event, and a support
      vector machines disambiguation model for identifying the context style (narrative
      or list). MEASUREMENTS: The authors, from the University of Wisconsin-Milwaukee,
      participated in the third i2b2 shared-task for challenges in natural language
      processing for clinical data: medication extraction challenge. With the
      performance metrics provided by the i2b2 challenge, the micro F1
      (precision/recall) scores are reported for both the horizontal and vertical
      level. RESULTS: Among the top 10 teams, Lancet achieved the highest precision at
      90.4% with an overall F1 score of 76.4% (horizontal system level with exact
      match), a gain of 11.2% and 12%, respectively, compared with the rule-based
      baseline system jMerki. By combining the two systems, the hybrid system further
      increased the F1 score by 3.4% from 76.4% to 79.0%. CONCLUSIONS: Supervised
      machine-learning systems with minimal external knowledge resources can achieve a
      high precision with a competitive overall F1 score.Lancet based on this learning
      framework does not rely on expensive manually curated rules. The system is
      available online at http://code.google.com/p/lancet/.

PMID- 20819866
TI  - Leveraging informatics for genetic studies: use of the electronic medical record
      to enable a genome-wide association study of peripheral arterial disease.
AB  - BACKGROUND: There is significant interest in leveraging the electronic medical
      record (EMR) to conduct genome-wide association studies (GWAS). METHODS: A
      biorepository of DNA and plasma was created by recruiting patients referred for
      non-invasive lower extremity arterial evaluation or stress ECG. Peripheral
      arterial disease (PAD) was defined as a resting/post-exercise ankle-brachial
      index (ABI) less than or equal to 0.9, a history of lower extremity
      revascularization, or having poorly compressible leg arteries. Controls were
      patients without evidence of PAD. Demographic data and laboratory values were
      extracted from the EMR. Medication use and smoking status were established by
      natural language processing of clinical notes. Other risk factors and
      comorbidities were ascertained based on ICD-9-CM codes, medication use and
      laboratory data. RESULTS: Of 1802 patients with an abnormal ABI, 115 had non
      atherosclerotic vascular disease such as vasculitis, Buerger's disease, trauma
      and embolism (phenocopies) based on ICD-9-CM diagnosis codes and were excluded.
      The PAD cases (66+/-11 years, 64% men) were older than controls (61+/-8 years,
      60% men) but had similar geographical distribution and ethnic composition. Among
      PAD cases, 1444 (85.6%) had an abnormal ABI, 233 (13.8%) had poorly compressible
      arteries and 10 (0.6%) had a history of lower extremity revascularization. In a
      random sample of 95 cases and 100 controls, risk factors and comorbidities
      ascertained from EMR-based algorithms had good concordance compared with manual
      record review; the precision ranged from 67% to 100% and recall from 84% to 100%.
      CONCLUSION: This study demonstrates use of the EMR to ascertain phenocopies,
      phenotype heterogeneity and relevant covariates to enable a GWAS of PAD.
      Biorepositories linked to EMR may provide a relatively efficient means of
      conducting GWAS.

PMID- 20819867
TI  - Errors and electronic prescribing: a controlled laboratory study to examine task
      complexity and interruption effects.
AB  - OBJECTIVE: To examine the effect of interruptions and task complexity on error
      rates when prescribing with computerized provider order entry (CPOE) systems, and
      to categorize the types of prescribing errors. DESIGN: Two within-subject
      factors: task complexity (complex vs simple) and interruption (interruption vs no
      interruption). Thirty-two hospital doctors used a CPOE system in a computer
      laboratory to complete four prescribing tasks, half of which were interrupted
      using a counterbalanced design. MEASUREMENTS: Types of prescribing errors, error
      rate, resumption lag, and task completion time. RESULTS: Errors in creating and
      updating electronic medication charts that were measured included failure to
      enter allergy information; selection of incorrect medication, dose, route,
      formulation, or frequency of administration from lists and drop-down menus
      presented by the CPOE system; incorrect entry or omission in entering
      administration times, start date, and free-text qualifiers; and omissions in
      prescribing and ceasing medications. When errors occurred, the error rates across
      the four prescribing tasks ranged from 0.5% (1 incorrect medication selected out
      of 192 chances for selecting a medication or error opportunities) to 16% (5
      failures to enter allergy information out of 32 error opportunities). Any impact
      of interruptions on prescribing error rates and task completion times was not
      detected in our experiment. However, complex tasks took significantly longer to
      complete (F(1, 27)=137.9; p<0.001) and when execution was interrupted they
      required almost three times longer to resume compared to simple tasks (resumption
      lag complex=9.6 seconds, SD=5.6; resumption lag simple=3.4 seconds, SD=1.7;
      t(28)=6.186; p<0.001). CONCLUSION: Most electronic prescribing errors found in
      this study could be described as slips in using the CPOE system to create and
      update electronic medication charts. Cues available within the user interface may
      have aided resumption of interrupted tasks making CPOE systems robust to some
      interruption effects. Further experiments are required to rule out any effect
      interruption might have on CPOE error rates.

PMID- 20819868
TI  - A network collaboration implementing technology to improve medication dispensing
      and administration in critical access hospitals.
AB  - We report how seven independent critical access hospitals collaborated with a
      rural referral hospital to standardize workflow policies and procedures while
      jointly implementing the same health information technologies (HITs) to enhance
      medication care processes. The study hospitals implemented the same electronic
      health record, computerized provider order entry, pharmacy information systems,
      automated dispensing cabinets (ADC), and barcode medication administration
      systems. We conducted interviews and examined project documents to explore
      factors underlying the successful implementation of ADC and barcode medication
      administration across the network hospitals. These included a shared culture of
      collaboration; strategic sequencing of HIT component implementation; interface
      among HIT components; strategic placement of ADCs; disciplined use and sharing of
      workflow analyses linked with HIT applications; planning for workflow
      efficiencies; acquisition of adequate supply of HIT-related devices; and
      establishing metrics to monitor HIT use and outcomes.

PMID- 20819869
TI  - Under-documentation of chronic kidney disease in the electronic health record in
      outpatients.
AB  - OBJECTIVE: To ascertain if outpatients with moderate chronic kidney disease (CKD)
      had their condition documented in their notes in the electronic health record
      (EHR). DESIGN: Outpatients with CKD were selected based on a reduced estimated
      glomerular filtration rate and their notes extracted from the Columbia University
      data warehouse. Two lexical-based classification tools (classifier and word
      counter) were developed to identify documentation of CKD in electronic notes.
      MEASUREMENTS: The tools categorized patients' individual notes on the basis of
      the presence of CKD-related terms. Patients were categorized as appropriately
      documented if their notes contained reference to CKD when CKD was present.
      RESULTS: The sensitivities of the classifier and word-count methods were 95.4%
      and 99.8%, respectively. The specificity of both was 99.8%. Categorization of
      individual patients as appropriately documented was 96.9% accurate. Of 107
      patients with manually verified moderate CKD, 32 (22%) lacked appropriate
      documentation. Patients whose CKD had not been appropriately documented were
      significantly less likely to be on renin-angiotensin system inhibitors or have
      urine protein quantified, and had the illness for half as long (15.1 vs 30.7
      months; p<0.01) compared to patients with documentation. CONCLUSION: Our studies
      show that lexical-based classification tools can accurately ascertain if
      appropriate documentation of CKD is present in a EHR. Using this method, we
      demonstrated under-documentation of patients with moderate CKD. Under-documented
      patients were less likely to receive CKD guideline recommended care. A tool that
      prompts providers to document CKD might shorten the time to implementing
      guideline-based recommendations.

PMID- 20819870
TI  - Developing syndrome definitions based on consensus and current use.
AB  - OBJECTIVE: Standardized surveillance syndromes do not exist but would facilitate
      sharing data among surveillance systems and comparing the accuracy of existing
      systems. The objective of this study was to create reference syndrome definitions
      from a consensus of investigators who currently have or are building syndromic
      surveillance systems. DESIGN: Clinical condition-syndrome pairs were catalogued
      for 10 surveillance systems across the United States and the representatives of
      these systems were brought together for a workshop to discuss consensus syndrome
      definitions. RESULTS: Consensus syndrome definitions were generated for the four
      syndromes monitored by the majority of the 10 participating surveillance systems:
      Respiratory, gastrointestinal, constitutional, and influenza-like illness (ILI).
      An important element in coming to consensus quickly was the development of a
      sensitive and specific definition for respiratory and gastrointestinal syndromes.
      After the workshop, the definitions were refined and supplemented with keywords
      and regular expressions, the keywords were mapped to standard vocabularies, and a
      web ontology language (OWL) ontology was created. LIMITATIONS: The consensus
      definitions have not yet been validated through implementation. CONCLUSION: The
      consensus definitions provide an explicit description of the current state-of-the
      art syndromes used in automated surveillance, which can subsequently be
      systematically evaluated against real data to improve the definitions. The method
      for creating consensus definitions could be applied to other domains that have
      diverse existing definitions.

PMID- 20819871
TI  - Migrating existing clinical content from ICD-9 to SNOMED.
AB  - OBJECTIVE: To identify challenges in mapping internal International
      Classification of Disease, 9th edition, Clinical Modification (ICD-9-CM) encoded
      legacy data to Systematic Nomenclature of Medicine (SNOMED), using SNOMED
      prescribed compositional approaches where appropriate, and to explore the mapping
      coverage provided by the US National Library of Medicine (NLM)'s SNOMED clinical
      core subset. DESIGN: This study selected ICD-CM codes that occurred at least 100
      times in the organization's problem list or diagnosis data in 2008. After
      eliminating codes whose exact mappings were already available in UMLS, the
      remainder were mapped manually with software assistance. RESULTS: Of the 2194
      codes, 784 (35.7%) required manual mapping. 435 of these represented concept
      types documented in SNOMED as deprecated: these included the qualifying phrases
      such as 'not elsewhere classified'. A third of the codes were composite,
      requiring multiple SNOMED code to map. Representing 45 composite concepts
      required introducing disjunction ('or') or set-difference ('without') operators,
      which are not currently defined in SNOMED. Only 47% of the concepts required for
      composition were present in the clinical core subset. Search of SNOMED for the
      correct concepts often required extensive application of knowledge of both
      English and medical synonymy. CONCLUSION: Strategies to deal with legacy ICD data
      must address the issue of codes created by non-taxonomist users. The NLM core
      subset possibly needs augmentation with concepts from certain SNOMED hierarchies,
      notably qualifiers, body structures, substances/products and organisms. Concept
      matching software needs to utilize query expansion strategies, but these may be
      effective in production settings only if a large but non-redundant SNOMED subset
      that minimizes the proportion of extensively pre-coordinated concepts is also
      available.

PMID- 20819872
TI  - Use of a codified medication process for documentation of home medications.
AB  - To determine the quality and completeness of the list of home medications
      documented by nurses using a codified process, authors conducted a comparative
      study of home medications using a non-codified and codified process for
      documentation of required data fields including drug, dose, route of
      administration, frequency, and schedule. Each documented home medication (DHM)
      was evaluated based on the ability to convert to an inpatient medication order.
      The home medication was classified as non-convertible if one or more of the
      required data fields were missing, inaccurate, or incomplete. The study compared
      176 patients with 1618 DHM in the non-codified group to 94 patients with 646 DHM
      in the codified group. All DHM could be converted to inpatient orders for 70% of
      the patients in the codified group compared with 42% in the non-codified group.
      Based on each DHM, the codified process resulted in 92% of the DHM being able to
      convert to inpatient orders compared with 82% for the non-codified process.
      Authors conclude that use of a codified process to document home medications has
      the potential to increase the number of complete drug entries and in the number
      of patients with a DHM list in which all of the medication entries have all of
      the dosing information.

PMID- 20819875
TI  - Primary HIV infection.

PMID- 20819874
TI  - Isoniazid resistance and death in patients with tuberculous meningitis:
      retrospective cohort study.
AB  - OBJECTIVE: To determine whether initial isoniazid resistance is associated with
      death during the treatment of tuberculous meningitis. DESIGN: Retrospective
      cohort study. SETTING: National Tuberculosis Surveillance System at the Centers
      for Disease Control in the United States. PARTICIPANTS: Patients with a clinical
      diagnosis of tuberculous meningitis, reported to the National Tuberculosis
      Surveillance System between 1 January 1993 and 31 December 2005. MAIN OUTCOME
      MEASURE: All cause mortality during antituberculous treatment. RESULTS: Between
      1993 and 2005, 1896 patients had a clinical diagnosis of tuberculous meningitis
      and positive cultures from any site. In 123 (6%) of these patients, isoniazid
      resistance was present on initial susceptibility testing. The unadjusted
      association between initial isoniazid resistance and subsequent death among these
      1896 patients did not reach statistical significance (odds ratio 1.38, 95%
      confidence interval 0.94 to 2.02). However, among 1614 patients with positive
      cerebrospinal fluid cultures, a significant unadjusted association was found
      between initial isoniazid resistance and subsequent death (odds ratio 1.61, 1.08
      to 2.40). This association increased after adjustment for age, race, sex, and HIV
      status (odds ratio 2.07, 1.30 to 3.29). CONCLUSIONS: Isoniazid resistance on
      initial susceptibility testing was associated with subsequent death among cases
      of tuberculous meningitis with positive cerebrospinal fluid cultures. Randomised
      controlled trials are needed to evaluate the optimal empirical regimen for
      treating patients with tuberculous meningitis who are at high risk for both
      initial isoniazid resistance and poor clinical outcomes.

PMID- 20819876
TI  - Tuberculous meningitis and resistance to isoniazid.

PMID- 20819879
TI  - Subspecialisation and despecialisation in anatomical pathology.
AB  - Subspecialisation in histopathology was anticipated to improve the quality of
      reporting, teaching and communication with the clinical team. Although there is
      little information available, there is a suggestion that subspecialised services
      are more expensive than services provided by general departments but are
      speedier, although even this improvement is now being compromised by requirements
      to doubly report some types of case. Departments considering adopting a
      subspecialist model should carefully consider the financial and organisational
      implications, and recognise that it is associated with reduced flexibility in
      case of vacancy or illness. Although individual pathologists report moving from
      subspecialist to more general practice with varying degrees of success (this was
      facilitated by general training, a brief period of subspecialisation, exposure to
      a general pool of straightforward cases from other specialities and a defined
      period of supervised retraining), there is no known example of an entire
      subspecialised department returning to provide a general service, and it is
      unclear as to how the difficulties likely to be encountered could be overcome.
      The original move to subspecialise was based on enthusiasm with little objective
      measurement of changes in cost or quality (or any input or output measure). Cost
      and quality associated with both general and subspecialist units are still poorly
      documented in the literature, and the need to establish baselines for these is a
      major challenge for pathologists. Further subspecialisation or any move to
      despecialise should be undertaken on the basis of such measures, which should be
      carefully monitored.

PMID- 20819880
TI  - Portal inflammation is associated with advanced histological changes in alcoholic
      and non-alcoholic fatty liver disease.
AB  - BACKGROUND: Fatty liver disease (FLD), of either alcoholic (AFLD) or non
      alcoholic (NAFLD) aetiologies, is characterised histologically by features that
      are lobulocentric that typically affect zone 3, in contrast with portal-based
      inflammation characteristics of other forms of chronic liver disease. AIM: The
      authors aimed to determine the prevalence and significance of portal inflammation
      in a cohort of adults diagnosed as having AFLD and NAFLD. METHODS: From a
      histology database, the authors identified 160 patients with biopsy proven AFLD
      and 214 with NAFLD diagnosed between 1991 and 2001. All liver biopsies were
      reviewed by one pathologist to evaluate various histological features. RESULTS:
      More than a mild degree of portal inflammation was found in 47% of AFLD compared
      with 30% in NAFLD subgroup. A higher degree of portal inflammation in AFLD was
      associated with a higher mean corpuscular volume, gamma glutamyl transferase
      (GGT) and alkaline phosphatase, and a lower platelet count and albumin, whereas
      in NAFLD this was associated with age, presence of diabetes, hypertension, body
      mass index (BMI), higher fasting blood glucose, cholesterol, alanine
      transaminase, GGT and ferritin. On regression analysis, portal inflammation was
      associated with the severity of steatosis (p=0.005), presence of ballooning
      (p=0.030) in NAFLD and severity of fibrosis in both AFLD and NAFLD (p<0.001).
      CONCLUSIONS: Portal inflammation is a common component of histological spectrum
      of both AFLD and NAFLD. In both conditions portal inflammation is associated with
      clinical and histological features suggestive of advanced disease.

PMID- 20819881
TI  - Variation and uncertainties in the classification of sudden unexpected infant
      deaths among paediatric pathologists in the UK: findings of a National Delphi
      Study.
AB  - AIMS: Presently, pathologists in the UK use diverse terminologies for the
      classification of sudden unexpected infant deaths, including 'unascertained,'
      'sudden unexpected death in infancy' (SUDI) and 'sudden infant death syndrome'
      (SIDS). This study uses the Delphi method to investigate the views of paediatric
      pathologists on their use of these terms in order to determine areas of
      consensus. METHODS: There were three Delphi rounds overall; in the final one,
      participants were asked to score each statement using a modified Likert scale (0
      9). The scores were analysed using non-parametric statistics, and statements in
      which the median score was <or=3 or >or=7 (approximately 70% agreement) were
      considered to have reached 'consensus agreement.' RESULTS: Twenty-five of the 36
      UK paediatric pathologists who were approached in the initial round contributed
      to all three rounds. There was consensus that 'SIDS' be used for unexplained
      sudden unexpected infant deaths that occurred during sleep. 'Infancy' was defined
      as up to 1 year of age, but there was no consensus regarding the lower age limit
      of SIDS. There was agreement that 'SUDI' be used for unexplained sudden infant
      deaths with a history of preceding illness, deaths with minor histological
      abnormalities of uncertain significance and co-sleeping-associated deaths. Most
      paediatric pathologists used 'unascertained' for findings suspicious of a non
      natural cause of death. There was consensus that co-sleeping-associated deaths
      should be classified as 'unascertained' if parents had consumed alcohol or used
      drugs in the preceding 24 h. CONCLUSIONS: The areas of consensus relating to
      terminology around SUDI and SIDS should guide future use by pathologists.
      However, there remains a significant lack of agreement, suggesting that
      acceptable alternative terms be identified for infant deaths which remain
      unexplained following autopsy in whom there are no suspicious features; the
      authors propose that 'unexplained SUDI,' followed by a comment, may represent the
      most factually correct compromise.

PMID- 20819882
TI  - Steroid therapy is associated with decreased numbers of dendritic cells and
      fibroblasts, and increased numbers of satellite cells, in the dystrophic skeletal
      muscle.
AB  - BACKGROUND: The possible therapeutic benefits of using steroids to enhance muscle
      strength and slow disease progression in Duchenne muscular dystrophy (DMD) and
      Becker muscular dystrophy (BMD) has been examined previously. In this
      investigation, it was hypothesised that steroid therapy is associated with
      morphological changes in the dystrophic muscle. OBJECTIVES AND METHODS: To test
      this hypothesis, two muscle biopsies were obtained (one biopsy before treatment,
      and the second 6 months following prednisone therapy) from 24 patients with
      dystrophies (18 DMD, 6 BMD). The participants were categorised into: control (6
      specimens, normal muscle), untreated and treated groups. The muscle was evaluated
      for ultrastructural changes using transmission electron microscopy (TEM).
      RESULTS: In the untreated group, the muscle fibres were degenerated and of
      variable sizes. The myofibrils were thin with either complete loss of bands
      and/or abnormal banding patterns. The Z-lines were irregularly spaced and loosely
      registered. The mitochondria of the myofibrils were small, few, spherical and
      irregularly distributed. Numerous dendritic cells (DCs) with euchromatic nuclei,
      and multiple and long dendrites, were seen among the myofibrils. The collagen
      fibres among the muscle fibres (endomysium) were numerous and large. The
      satellite cells had euchromatic nuclei with clumps of heterochromatin. In the
      treated group, the muscle fibres had a relatively uniform size with occasional
      fibres showing partial degeneration. The myofibrils had a relatively similar
      diameter comparable to that of normal muscle .The degenerated areas were small in
      size with occasional foci showing loss of banding pattern, and abnormal short
      bands with thick and hazy Z-lines. The mitochondria of the myofibrils were
      numerous, spherical, small in size and regularly arranged between the myofibrils.
      Few DCs, with heterochromatic nuclei, and few and short dendrites appeared
      between the myofibrils. The collagen fibres between the muscle fibres
      (endomysium) were numerous and large. As compared with the treated group, there
      was a statistically significant increase (p<0.05) in the numbers of DCs (0.7+/
      0.2 vs 1.6+/-0.3) and fibroblasts (1.9+/-0.2 vs 2.9 +/-0.3) in the untreated
      group. Alternatively, there was a statistically significant decrease (p<0.05) in
      the numbers of satellite cells (1.2+/-0.2 vs 0.6+/-0.1). CONCLUSION: The ability
      of steroids to induce ultrastructural features of improvement supports the notion
      that they have beneficial therapeutic role. The clinical ramifications of these
      observations mandate further studies.

PMID- 20819883
TI  - Point-of-care diagnostic tests for childhood urinary-tract infection: phase
      contrast microscopy for bacteria, stick testing, and counting white blood cells.
AB  - AIM: To evaluate point-of-care testing for childhood urinary-tract infections
      (UTI). METHOD: Point-of-care testing of prospectively collected sequential paired
      urines was compared with quantitative culture after serial dilution in 203
      children, of whom 36 had UTIs. Proportionate reduction in uncertainty (PRU) plots
      were used to compare between methods and with published values. RESULTS: Phase
      contrast microscopy for bacteria, as with culturing a single urine and using a
      threshold of 10(5) bacteria/ml, was 100% sensitive, making it powerful to rule
      UTIs out. The specificity was slightly lower than urine culture (0.860 vs 0.925)
      except in girls >9 years where vaginal Lactobacillus contamination reduced it to
      0.61, but this increased to 0.81 when 'urethral stream' urines were collected.
      Nitrite positivity is highly specific at 0.985, making it powerful at ruling UTIs
      in, but its low sensitivity (0.61) makes it unsafe to rule UTIs out. A PRU plot
      of 16 previous studies confirmed this. Though the presence of urinary white blood
      cells (WBC) correlates with UTI, whether tested by point-of-care of laboratory
      microscopy or by stick testing, the coefficient of determination is too low to
      make them clinically useful, alone or combined with nitrite analysis. Seventeen
      other studies confirmed this. CONCLUSION: Phase-contrast microscopy can rule out
      UTIs as reliably as urine culture but is immediate, which may be clinically
      important. To interpret positive results reliably, girls >9 years must collect a
      'urethral stream' urine. While nitrite positivity is useful to rule UTIs in,
      negative results are unreliable. Urinary WBC testing has little value.

PMID- 20819885
TI  - HIV infection associated with scleroderma: report of two new cases.

PMID- 20819886
TI  - Is there a relationship between familial adenomatous polyposis and focal nodular
      hyperplasia?

PMID- 20819887
TI  - Licensing drugs for diabetes.

PMID- 20819888
TI  - Commentary: What can we learn from the continuing regulatory focus on the
      thiazolidinediones?

PMID- 20819889
TI  - Rosiglitazone: what went wrong?

PMID- 20819890
TI  - Alterations in end-of-life support in the pediatric intensive care unit.
AB  - OBJECTIVE: Our purpose was to examine alterations in end-of-life support in a
      multiinstitutional sample of PICUs. METHODS: This was a retrospective,
      descriptive study. Variables collected included end-of-life support category,
      race, length of stay, operative status, reason for admission, and Pediatric Index
      of Mortality 2 score, as well as the number of ICU beds and the presence of
      trainees. RESULTS: There were 1745 deaths at 35 institutions between January 1,
      2004, and September 30, 2005. Of those, 1263 had complete data and were analyzed.
      The end-of-life support category distribution was as follows: brain death, 296
      (23%); do not resuscitate, 205 (16%); limitation of support, 36 (3%); withdrawal
      of support, 579 (46%); no limitation, 124 (10%); no advance directives, 23 (2%).
      For further analyses, end-of-life support categories were grouped as limitation
      (ie, do not resuscitate, limitation of support, or withdrawal of support) versus
      no limitation (ie, no limitation or no advance directive). Brain death was not
      included in further analyses. The majority of deaths were in the limitation group
      (n=820 [85%]), and 12 (40%) of 30 institutions had 100% of deaths in this group.
      There were significant differences between institutions (P<.001). Decisions for
      limitation were seen less frequently in the black race (112 [76%] of 147 deaths;
      P=.037) and in institutions with no trainees (56 [69%] of 81 deaths; P<.001).
      CONCLUSIONS: Decisions to limit support are common. Black race and an absence of
      trainees are associated with decreased frequency of limitation decisions.

PMID- 20819891
TI  - CHIT1 mutations: genetic risk factor for severe asthma with fungal sensitization?
AB  - Fungi can exacerbate symptoms in patients with asthma. To our knowledge, genetic
      risk factors for fungal-associated asthma have not been described. We present
      here the cases of 6 children who carried the diagnosis of severe asthma with
      fungal sensitization, 3 of whom were treated with and responded clinically to
      itraconazole therapy. All 6 patients were heterozygous for a 24-base pair
      duplication in the CHIT1 gene, which has been associated with decreased levels of
      circulating chitotriosidase and susceptibility to fungal infection.

PMID- 20819892
TI  - Immunogenicity and safety of MF59-adjuvanted H5N1 influenza vaccine from infancy
      to adolescence.
AB  - OBJECTIVE: This study evaluated the immunogenicity, safety, and tolerability of a
      MF59-adjuvanted H5N1 vaccine in a population 6 months through 17 years of age.
      METHODS: Healthy subjects 6 to <36 months, 3 to <9 months, and 9 to <18 years of
      age were assigned randomly to receive 2 doses of either a MF59-adjuvanted H5N1
      vaccine (7.5 MUg/dose) or a MF59-adjuvanted trivalent seasonal influenza control
      vaccine (15 MUg/dose for each antigen). Immunogenicity against the
      A/Vietnam/1194/2004-like vaccine strain was measured before and 3 weeks after the
      2-dose primary series, through hemagglutination inhibition (HI), single radial
      hemolysis (SRH), and microneutralization. Local and systemic reactions were
      recorded. RESULTS: A total of 335 subjects received the H5N1 vaccine, and 137
      subjects received the seasonal vaccine. Rates of seroprotection (HI titer of
      >=40) against the H5N1 vaccine antigen were 97% for children 6 to 36 months and 3
      to 9 years of age and 89% for older children. All subjects seroconverted in the
      SRH assay. Microneutralization titers of >=40 were achieved by 99% of subjects,
      and >=98% of subjects, respectively. Local reactions, particularly injection site
      pain in older children, were common, generally mild to moderate in nature, and
      transient and resolved spontaneously. Up to 5% of participants. There were no
      vaccine-related serious adverse events in either group. CONCLUSIONS: In this
      pediatric population, MF59-adjuvanted H5N1 vaccine was highly immunogenic, had a
      good safety profile, reactogenicity comparable with that of an adjuvanted
      seasonal influenza control vaccine.

PMID- 20819894
TI  - Spirometry use among pediatric primary care physicians.
AB  - OBJECTIVE: This study explores the use of spirometry in primary care settings.
      METHODS: A 4-page survey was mailed to a national, random sample of office-based
      family physicians and pediatricians. Survey items addressed knowledge, attitudes,
      and practices regarding spirometry and standardized clinical vignettes. Data were
      analyzed by using chi2 tests and multivariate logistic regression. RESULTS: Among
      the 360 respondents who provided care to children with asthma, 52% used
      spirometry in clinical practice, whereas 80% used peak flow meters and 10% used
      no lung function tests. Only 21% routinely used spirometry for all guideline
      recommended clinical situations. More family physicians than pediatricians
      reported using spirometry (75% vs 35%; P<.0001), and family physicians were more
      comfortable in interpreting spirometric results (50% vs 25%; P<.0001). Only one
      half of respondents interpreted correctly the spirometric results in a
      standardized clinical vignette, and the frequency of underrating asthma severity
      increased with the inclusion of spirometric results. The most common barriers to
      the use of spirometry, that is, time and training, were cited more often by
      physicians who did not use spirometry. Two-thirds of respondents agreed that they
      would want additional training regarding implementing spirometry in their
      clinical practices. CONCLUSIONS: The use of spirometry in primary care settings
      for children with asthma does not conform to national guidelines. Widespread
      implementation of national asthma guidelines likely would require a major
      educational initiative to address deficiencies in spirometry interpretation and
      other barriers.

PMID- 20819893
TI  - Practice and child characteristics associated with influenza vaccine uptake in
      young children.
AB  - OBJECTIVES: The objective of this study was to determine both practice and child
      characteristics and practice strategies associated with receipt of influenza
      vaccine in young children during the 2004-2005 influenza season, the first season
      for the universal influenza vaccination recommendation for all children who are
      aged 6 to 23 months. METHODS: Clinical and demographic data from randomly
      selected children who were aged 6 to 23 months were obtained by chart review from
      a community-based cohort study in 3 US counties. The proportion of children who
      were vaccinated by April 5, 2005, in each practice was obtained. For assessment
      of practice characteristics and strategies, sampled practices received a self
      administered practice survey. Practice and child characteristics that predicted
      complete influenza vaccination were determined by using multinomial logistic
      regression. RESULTS: Forty-six (88%) of 52 sampled practices completed the survey
      and permitted chart reviews. Of 2384 children who were aged 6 to 23 months and
      were studied, 27% were completely vaccinated. The proportion of children who were
      completely vaccinated varied widely among practices (0%-71%). Most (87%)
      practices implemented >=1 vaccination strategy. Complete influenza vaccination
      was associated with 3 practice characteristics: suburban location, lower patient
      volume, and vaccination strategies of evening/weekend vaccine clinics; with child
      characteristics of younger age, existing high-risk conditions, >=6 well visits to
      the practice by 3 years of age, and any practice visit from October through
      January. CONCLUSIONS: Modifiable factors that were associated with increased
      influenza vaccination coverage included October to January practice visits and
      evening/weekend vaccine clinics.

PMID- 20819895
TI  - Impact of rapid leukodepletion on the outcome of severe clinical pertussis in
      young infants.
AB  - OBJECTIVES: Bordetella pertussis is a common, underrecognized, and vaccine
      preventable cause of critical illness with a high mortality in infants worldwide.
      Patients with severe cases present with extreme leukocytosis and develop
      refractory hypoxemia and pulmonary hypertension that is unresponsive to maximal
      intensive care. This may reflect a hyperviscosity syndrome from the raised white
      blood cell (WBC) count. Case reports suggest improved outcomes with exchange
      transfusion to reduce the WBC count. Our objective was to quantify possible
      benefits of aggressive leukodepletion. METHODS: We, as a regional PICU and
      extracorporeal membrane oxygenation referral center, adopted a strategy of
      aggressive leukodepletion in January 2005. The impact of this strategy on crude
      and case mix-adjusted survival of all infants who were critically ill with B
      pertussis were compared with control subjects from January 2001 to December 2004
      and Extracorporeal Life Support Organisation registry data. RESULTS: Nineteen
      infants (7 [37%] boys) received intensive care for B pertussis from 2001 to 2009.
      Admission WBC counts were equivalent in 2 time periods: 2001-2004 (mean:
      52,000/MUL) and 2005-2009 (mean: 75,000/MUL). In 2001-2004, 5 (55%) of 9 patients
      survived the ICU. Between 2005 and 2009, 9 (90%) of 10 patients survived. When
      case-mix adjustment for age, WBC count, and extracorporeal membrane oxygenation
      referral were considered, the 2001-2004 predicted survival (4.4 [49%] of 9.0) was
      equivalent to the observed mortality (4.0 [44%] of 9.0). Between 2005 and 2009,
      observed mortality (1.0 [10%] of 10.0) was significantly better than predicted
      (4.7 [47%] of 10.0). CONCLUSIONS: Leukodepletion should be considered in
      critically ill infants with B pertussis and leukocytosis.

PMID- 20819897
TI  - Clinical report--physicians' roles in coordinating care of hospitalized children.
AB  - The care of hospitalized children and adolescents has become increasingly complex
      and often involves multiple physicians beyond the traditional primary care
      pediatrician. Hospitalists, medical subspecialists, surgical specialists, and
      hospital attending physicians may all participate in the care of hospitalized
      children and youth. This report summarizes the responsibilities of the
      pediatrician and other involved physicians in ensuring that children receive
      coordinated and comprehensive medical care delivered within the context of their
      medical homes as inpatients, and that care is appropriately continued on an
      outpatient basis.

PMID- 20819896
TI  - Bisphenol A and related compounds in dental materials.
AB  - CONTEXT: Dental sealants and composite filling materials containing bisphenol A
      (BPA) derivatives are increasingly used in childhood dentistry. Evidence is
      accumulating that BPA and some BPA derivatives can pose health risks attributable
      to their endocrine-disrupting, estrogenic properties. OBJECTIVES: To
      systematically compile and critically evaluate the literature characterizing BPA
      content of dental materials; to assess BPA exposures from dental materials and
      potential health risks; and to develop evidence-based guidance for reducing BPA
      exposures while promoting oral health. METHODS: The extant toxicological
      literature and material safety data sheets were used as data sources. RESULTS:
      BPA is released from dental resins through salivary enzymatic hydrolysis of BPA
      derivatives, and BPA is detectable in saliva for up to 3 hours after resin
      placement. The quantity and duration of systemic BPA absorption is not clear from
      the available data. Dental products containing the bisphenol A derivative
      glycidyl dimethacrylate (bis-GMA) are less likely to be hydrolyzed to BPA and
      have less estrogenicity than those containing bisphenol A dimethacrylate (bis
      DMA). Most other BPA derivatives used in dental materials have not been evaluated
      for estrogenicity. BPA exposure can be reduced by cleaning and rinsing surfaces
      of sealants and composites immediately after placement. CONCLUSIONS: On the basis
      of the proven benefits of resin-based dental materials and the brevity of BPA
      exposure, we recommend continued use with strict adherence to precautionary
      application techniques. Use of these materials should be minimized during
      pregnancy whenever possible. Manufacturers should be required to report complete
      information on the chemical composition of dental products and encouraged to
      develop materials with less estrogenic potential.

PMID- 20819898
TI  - Iron supplements reduce the risk of iron deficiency anemia in marginally low
      birth weight infants.
AB  - OBJECTIVE: Low birth weight infants are at risk for iron deficiency (ID). Most
      LBW infants have marginally low birth weight (MLBW, 2000-2500 g) and it is not
      known whether they benefit from iron supplements. The objective of this trial was
      to study the effects of iron supplementation in MLBW infants. METHOD: In a
      randomized controlled trial, we assigned 285 healthy, MLBW infants to receive
      iron supplements at a dose of 0 (placebo), 1, or 2 mg/kg per day between 6 weeks
      and 6 months of age. Hemoglobin levels, ferritin levels, transferrin saturation,
      mean cell volume, and transferrin receptor levels were analyzed at 6 months.
      Growth and morbidity were monitored. RESULTS: Iron supplementation resulted in
      significant dose-dependent effects on hemoglobin and all iron status indicators
      at 6 months. The prevalence of ID at 6 months was 36% in the placebo group, 8.2%
      in the 1 mg/kg per day group, and 3.8% in the 2 mg/kg per day group (P<.001). The
      prevalence rates of ID anemia (IDA) were 9.9%, 2.7%, and 0%, respectively
      (P=.004). Among infants who were exclusively breastfed at 6 weeks, the prevalence
      of IDA was 18% in the placebo group. There were no significant differences
      between groups in growth or morbidity. CONCLUSIONS: MLBW infants have relatively
      high risks of ID and IDA, especially if they are breastfed. Iron supplementation
      at 2 mg/kg per day from 6 weeks to 6 months reduces this risk effectively, with
      no short-term adverse effects on morbidity or growth.

PMID- 20819899
TI  - Policy statement--postnatal corticosteroids to prevent or treat bronchopulmonary
      dysplasia.
AB  - The purpose of this revised statement is to review current information on the use
      of postnatal glucocorticoids to prevent or treat bronchopulmonary dysplasia in
      the preterm infant and to make updated recommendations regarding their use. High
      dose dexamethasone (0.5 mg/kg per day) does not seem to confer additional
      therapeutic benefit over lower doses and is not recommended. Evidence is
      insufficient to make a recommendation regarding other glucocorticoid doses and
      preparations. The clinician must use clinical judgment when attempting to balance
      the potential adverse effects of glucocorticoid treatment with those of
      bronchopulmonary dysplasia.

PMID- 20819900
TI  - Reduced endothelial progenitor cells in children with hemodialysis but not
      predialysis chronic kidney disease.
AB  - In adults with chronic kidney disease (CKD), reduced levels of vasculoprotective
      endothelial progenitor cells (EPCs) may contribute to their increased risk of
      cardiovascular disease. Children with CKD also show signs of cardiovascular
      disease. However, to our knowledge, there have been no studies on circulating EPC
      levels in pediatric patients with CKD. We investigated CD34+KDR+ EPC numbers by
      using flow cytometry in 15 children with predialysis CKD, 13 children on
      hemodialysis, and 18 age-matched healthy controls. Children on hemodialysis
      showed 47% reduced EPC levels compared with controls, whereas no significant
      difference was found for patients with predialysis CKD. Lower EPC levels were
      found in patients with higher levels of inflammatory marker high-sensitivity C
      reactive protein. Our data show, for the first time, that children on
      hemodialysis have reduced CD34+KDR+ EPC levels, which potentially contributes to
      their increased cardiovascular risk. In children with predialysis CKD, a decline
      in renal function was not associated with reduced EPC levels, which may reflect a
      capacity for preservation of the endogenous repair system during relatively
      moderate disturbances of the systemic environment.

PMID- 20819901
TI  - Evaluation of the standardized assessment of concussion in a pediatric emergency
      department.
AB  - OBJECTIVE: The Standardized Assessment of Concussion (SAC) is a validated tool
      for identifying the effects of mild traumatic brain injury (mTBI). Previous
      research focused on sport-related sideline evaluation of adolescents and adults.
      Our goal was to evaluate performance of the SAC among subjects with and without
      head injury in a pediatric emergency department (ED). METHODS: This was an
      observational study of children 6 to 18 years of age who presented to an ED with
      blunt head injury (case-patients) or minor extremity injury (controls). SAC and
      graded-symptom-checklist scores were compared. American Academy of Neurology
      concussion grades, presence of loss of consciousness and posttraumatic amnesia
      were also compared with SAC and graded-symptom-checklist scores among case
      patients. RESULTS: Three hundred forty-eight children were enrolled. SAC scores
      trended lower (greater cognitive deficits) for case-patients compared with
      controls but did not reach significance. Graded-symptom-checklist scores were
      significantly higher among case-patients. Presence of altered mental status
      magnified this effect. There was no correlation between SAC scores and other
      indicators of mTBI. There was a positive correlation between graded-symptom
      checklist scores and posttraumatic amnesia and American Academy of Neurology
      concussion grade. CONCLUSIONS: The graded symptom checklist reliably identified
      mTBI symptoms for all children aged 6 years and older. SAC scores tended to be
      lower for case-patients compared with controls but did not reach significance.
      Patients with altered mental status at the time of injury manifest an increased
      number and severity of symptoms. Additional research into strategies to identify
      cognitive deficits related to mTBI and classify mTBI severity in children is
      needed.

PMID- 20819902
TI  - Review of issue: the impact of time of day, mood, and caregiver stress on
      function in patients with dementia.

PMID- 20819903
TI  - Unappreciated but not unimportant: health disparities in the risk for cervical
      insufficiency.

PMID- 20819904
TI  - Transmural ablation of all the pulmonary veins: is it the Holy Grail for cure of
      atrial fibrillation?

PMID- 20819905
TI  - Travelling waves in a network of SIR epidemic nodes with an approximation of weak
      coupling.
AB  - A 1D lattice of coupled susceptible/infected/removed (SIR) epidemic centres is
      considered numerically and analytically. We describe a mechanism for the
      interaction between nodes in an SIR network, i.e. for the migration process of
      individuals between epidemic centres with a finite-characteristic time. More
      specifically, we study a model for a weakly coupled population distributed
      between the interacting centres with a diffusion-type migration process. A 1D
      lattice of SIR nodes is studied numerically. Travelling wave-like solutions
      preserving their shape and speed are found over a wide parameter range. For weak
      coupling, the main part of the travelling wave is well approximated by the
      limiting SIR solution. Explicit formulae are found for the speed of the
      travelling waves and compared with the results of numerical simulation.

PMID- 20819906
TI  - Remarkable abundance and evolution of mobile group II introns in Wolbachia
      bacterial endosymbionts.
AB  - The streamlined genomes of ancient obligate endosymbionts generally lack
      transposable elements, as a consequence of their intracellular confinement. Yet,
      the genomes of Wolbachia, one of the most abundant bacterial endosymbionts on
      Earth, are littered with transposable elements, in particular insertion sequences
      (ISs). This paradox raises the question of whether or not such a mobile DNA
      proliferation reflects a special feature of ISs. In this study, we focused on
      another class of transposable elements, group II introns, and conducted an in
      depth analysis of their content and the microevolutionary processes responsible
      for their dynamics within Wolbachia genomes. We report an exceptionally high
      intron abundance and striking differences in copy numbers between Wolbachia
      strains as well as between intron families. Our bioinformatics and experimental
      results provide strong evidence that intron diversity is mainly caused by recent
      (and perhaps ongoing) mobility and horizontal transfers. Our data also support
      several temporally independent intron invasions during Wolbachia evolution.
      Furthermore, group II intron spread in some Wolbachia strains may be regulated
      through gene conversion-mediated inactivation of intron copies. Finally, we found
      introns to be involved in numerous genomic rearrangements. This underscores the
      high recombinogenic potential of group II introns, contrary to general
      expectations. Overall, our study represents the first comprehensive analysis of
      group II intron evolutionary dynamics in obligate intracellular bacteria. Our
      results show that bacterial endosymbionts with reduced genomes can sustain high
      loads of mobile group II introns, as hypothesized for the endosymbiont ancestor
      of mitochondria during early eukaryote evolution.

PMID- 20819907
TI  - Reconstructing population histories from single nucleotide polymorphism data.
AB  - Population genetics encompasses a strong theoretical and applied research
      tradition on the multiple demographic processes that shape genetic variation
      present within a species. When several distinct populations exist in the current
      generation, it is often natural to consider the pattern of their divergence from
      a single ancestral population in terms of a binary tree structure. Inference
      about such population histories based on molecular data has been an intensive
      research topic in the recent years. The most common approach uses coalescent
      theory to model genealogies of individuals sampled from the current populations.
      Such methods are able to compare several different evolutionary scenarios and to
      estimate demographic parameters. However, their major limitation is the enormous
      computational complexity associated with the indirect modeling of the
      demographies, which limits the application to small data sets. Here, we propose a
      novel Bayesian method for inferring population histories from unlinked single
      nucleotide polymorphisms, which is applicable also to data sets harboring large
      numbers of individuals from distinct populations. We use an approximation to the
      neutral Wright-Fisher diffusion to model random fluctuations in allele
      frequencies. The population histories are modeled as binary rooted trees that
      represent the historical order of divergence of the different populations. A
      combination of analytical, numerical, and Monte Carlo integration techniques are
      utilized for the inferences. A particularly important feature of our approach is
      that it provides intuitive measures of statistical uncertainty related with the
      estimates computed, which may be entirely lacking for the alternative methods in
      this context. The potential of our approach is illustrated by analyses of both
      simulated and real data sets.

PMID- 20819908
TI  - Activation and potentiation of human GABAA receptors by non-dioxin-like PCBs
      depends on chlorination pattern.
AB  - The neurotoxic potential of non-dioxin-like polychlorinated biphenyls (NDL-PCBs)
      is characterized by disruption of presynaptic processes, including calcium
      homeostasis and neurotransmitter transport. Recently, using a limited set of
      congeners, we demonstrated that PCB28 and PCB52 can potentiate postsynaptic
      GABA(A) receptors. In the present study, effects of 20 NDL-PCBs and 2 dioxin-like
      PCBs, selected based on their chemical variation and abundance in the
      environment, on human GABA(A) receptors were investigated. GABA(A) receptors were
      expressed in Xenopus oocytes, and NDL-PCB effects were determined using the two
      electrode voltage-clamp technique. Results demonstrate that lower chlorinated
      PCB19, PCB28, PCB47, PCB51, PCB52, PCB95, and PCB100 act as a partial agonists
      (at low receptor occupancy), i.e., potentiating the receptor response during
      coapplication with GABA (at EC(20)). Importantly, PCB19, PCB47, PCB51, and PCB100
      can also act as full agonist, i.e., activate the GABA(A) receptor in the absence
      of GABA. Potentiation and activation of the GABA(A) receptor is concentration
      dependent and limited to NDL-PCBs that have 3-5 chlorine atoms, 1-3 ortho
      substitutions, an equal number (0-1) of meta-substitutions on both phenyl rings,
      and do not have an adjacent para- and meta-substitution on the same phenyl ring.
      Activation and potentiation of the GABA(A) receptor by PCB47, the most potent
      congener (lowest observed effect concentration of 10nM), is attenuated when
      coapplied with PCB19, PCB28, PCB153, or PCB180, indicative for competitive
      binding. Considering the importance of GABA-ergic signaling for brain
      development, motor coordination, learning, and memory, this mode of action can
      contribute to the previously observed NDL-PCB-induced neurobehavioral and
      neurodevelopmental effects and should be included in human risk assessment.

PMID- 20819909
TI  - An integrated genomic analysis of aryl hydrocarbon receptor-mediated inhibition
      of B-cell differentiation.
AB  - The aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) alters differentiation of B cells and suppresses antibody production. A
      combination of whole-genome, microarray-based chromatin immunoprecipitation (ChIP
      on-chip), and time course gene expression microarray analysis was performed on
      the mouse B-cell line CH12.LX following exposure to lipopolysaccharide (LPS) or
      LPS and TCDD to identify the primary and downstream transcriptional elements of B
      cell differentiation that are altered by the AHR. ChIP-on-chip analysis
      identified 1893 regions with a significant increase in AHR binding with TCDD
      treatment. Transcription factor binding site analysis on the ChIP-on-chip data
      showed enrichment in AHR response elements. Other transcription factors showed
      significant coenrichment with AHR response elements. When ChIP-on-chip regions
      were compared with gene expression changes at the early time points, 78 genes
      were identified as potential direct targets of the AHR. AHR binding and
      expression changes were confirmed for a subset of genes in primary mouse B cells.
      Network analysis examining connections between the 78 potential AHR target genes
      and three transcription factors known to regulate B-cell differentiation
      indicated multiple paths for potential regulation by the AHR. Enrichment analysis
      on the differentially expressed genes at each time point evaluated the downstream
      impact of AHR-regulated gene expression changes on B-cell-related processes. AHR
      mediated impairment of B-cell differentiation occurred at multiple nodes of the B
      cell differentiation network and potentially through multiple mechanisms
      including direct cis-acting effects on key regulators of B-cell differentiation,
      indirect regulation of B-cell differentiation-related pathways, and
      transcriptional coregulation of target genes by AHR and other transcription
      factors.

PMID- 20819910
TI  - Analysis of the CYP1A1 mRNA dose-response in human keratinocytes indicates that
      relative potencies of dioxins, furans, and PCBs are species and congener
      specific.
AB  - Reports indicate that toxic equivalency factors (TEFs) based primarily on rodent
      data do not accurately predict in vitro human responsiveness to certain dioxin
      like chemicals (DLCs). To investigate this in cells responsive to dioxins and
      relevant to chloracne, normal human epidermal keratinocytes were treated with
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and several DLCs, each with a TEF
      value of 0.1, representing three classes of congeners. We estimated half maximal
      effective concentration (EC50)-based donor-specific relative potency (REP) values
      for cytochrome P450 1A1 (CYP1A1) messenger RNA (mRNA) induction for TCDD,
      1,2,3,6,7,8-hexachlorodibenzo-p-dioxin (HxCDD), 2,3,7,8-tetrachlorodibenzofuran
      (TCDF), 1,2,3,6,7,8-hexachlorodibenzofuran (HxCDF), and 3,3',4,4',5
      pentachlorobiphenyl (PCB 126). We also determined EC50-based population-level REP
      values (n = 4) for CYP1A1 mRNA induction for TCDD, HxCDF, and PCB 126.
      Furthermore, an alternative factor, the relative threshold factor (RTF) based on
      the low end (threshold) of the dose-response curve, was calculated. Our results
      demonstrated that HxCDF had a population-based REP value of 0.98, 9.8-fold higher
      than its assigned TEF value of 0.1. Conversely, PCB 126 had an REP value of
      0.0027 and an RTF of 0.0022, 37-fold and 45-fold less than its assigned TEF of
      0.1, respectively. The REP values for HxCDD and TCDF were 0.24 and 0.10,
      respectively, similar to their assigned value of 0.1. Therefore, although the
      DLCs tested in the current study all possessed the same assigned TEF value of
      0.1, congener-specific differences in REPs and RTFs were observed for human
      keratinocytes. These congener-specific discrepancies are likely because of
      differences in interspecies factors that have yet to be defined.

PMID- 20819911
TI  - Deviations from Haber's Law for multiple measures of acute lung injury in
      chlorine-exposed mice.
AB  - Chlorine gas is considered a chemical threat agent that can cause acute lung
      injury. Studies in the early 20th century on war gases led Haber to postulate
      that the dose of an inhaled chemical expressed as the product of gas
      concentration and exposure time leads to a constant toxicological effect (Haber's
      Law). In the present work, mice were exposed to a constant dose of chlorine (100
      ppm-h) delivered using different combinations of concentration and time (800
      ppm/7.5 min, 400 ppm/15 min, 200 ppm/30 min, and 100 ppm/60 min). Significant
      effects of exposure protocol on survival evaluated 6 h after exposure were
      observed, ranging from 0% for the 7.5-min exposure to 100% for the 30- and 60-min
      exposures. Multiple parameters indicative of lung injury were examined to
      determine if any aspects of lung injury were differentially affected by the
      exposure protocols. Most parameters (pulmonary edema, neutrophil influx, and
      levels of protein, immunoglobulin M, and the chemokine KC [Cxcl1] in lavage
      fluid) indicated that lung injury was most pronounced for the 15-min exposure and
      least for the 60-min exposure. In contrast, changes in pulmonary function at
      baseline and in response to inhaled methacholine were similar following the three
      exposure regimens. The results indicate that the extent of lung injury following
      chlorine inhalation depends not only on total dose but also on the specifics of
      exposure concentration and time, and they suggest that evaluation of
      countermeasures against chlorine-induced lung injury should be performed using
      multiple types of exposure scenarios.

PMID- 20819912
TI  - Chronic percutaneous gallstone discharge following videothoracoscopic
      decortication.
AB  - Computed tomographic imaging is not recommended as an essential prerequisite in
      surgery for pleuro-pulmonary sepsis in the current guidelines. We highlight one
      consequent pitfall and its sequelae. We report the discharge of gallstones
      through a healed intercostal drain site four months following video-assisted
      thoracic surgery for early pleural empyema secondary to missed calculous
      gallstone disease. The importance of awareness and a high index of suspicion to
      diagnose the underlying extra-thoracic cause of a right-sided pleural collection
      in a patient with a previous history of gallstone disease cannot be
      overemphasised.

PMID- 20819913
TI  - Do women consult more than men? A review of gender and consultation for back pain
      and headache.
AB  - OBJECTIVES: Because women consult their general practitioners more frequently on
      average than men, it is commonly assumed that they consult more for all symptoms
      and conditions. This assumption is reinforced by qualitative studies reporting a
      widespread reluctance to consult by men. However, few studies directly compare
      consultation in men and women experiencing similar symptoms or conditions.
      METHODS: A systematic review of the evidence on gender and consultation for two
      common symptoms, back pain and headache. Extensive electronic searches identified
      15 papers reporting the relationship between gender and help-seeking for back
      pain and 11 papers for headache. Two independent reviewers assessed articles for
      inclusion and extracted data from eligible studies. RESULTS: Few studies compared
      consultation patterns for these symptoms among men and women known to have
      experienced the symptom. The quality of the studies was variable. Overall,
      evidence for greater consultation by women with back pain was weak and
      inconsistent. Among those with back pain, the odds ratios for women seeking help,
      compared with men, ranged from 0.6 (95% confidence intervals 0.3, 1.2, adjusted
      only for age) to 2.17 (95% confidence intervals 1.35, 3.57, unadjusted), although
      none of the reported odds ratio, below 1.00 was statistically significant. The
      evidence for women being more likely to consult for headache was a little
      stronger. Five studies showed a statistically elevated odds ratio, and none
      suggested that men with headache symptoms were more likely to consult than women
      with headache symptoms. Limitations to the studies are discussed. CONCLUSION:
      Given the strength of assumptions that women consult more readily for common
      symptoms, the evidence for greater consultation amongst women for two common
      symptoms, headache and back pain, was surprisingly weak and inconsistent,
      especially with respect to back pain.

PMID- 20819914
TI  - Storylines of self-management: narratives of people with diabetes from a
      multiethnic inner city population.
AB  - OBJECTIVES: to analyse the narratives of people with diabetes to inform the
      design of culturally congruent self-management education programmes. METHODS: the
      study was based on quasi-naturalistic story-gathering; i.e. making real-time
      field notes of stories shared spontaneously in diabetes self-management education
      groups in a socioeconomically deprived London borough. Eighty-two adults aged 25
      86, from six minority ethnic groups who were in the intervention arm of a
      randomized controlled trial of story-sharing, participated. Stories were
      translated in real time by the facilitator or group members. Ethnographic field
      notes were transcribed, and analysed thematically (to identify self-management
      domains raised by participants) and interpretively for over-arching storylines
      (i.e. considering how self-management domains were contextualized and made
      meaningful in personal narratives). Analysis was informed by both biomedical and
      sociological theories of self-management. RESULTS: people with diabetes
      identified seven self-management domains: knowledge; diet; exercise; medication;
      foot care; self-monitoring; and attending check-ups. Interpretive analysis
      revealed eight illness storylines within which these practical issues acquired
      social meaning and moral worth: becoming sick; rebuilding spoiled identity;
      becoming a practitioner of self-management; living a disciplined and balanced
      life; mobilizing a care network; navigating and negotiating in the health care
      system; managing the micro-morality of self-management 'choices'; and taking
      collective action. CONCLUSION: living with diabetes involves both medically
      recommended behaviours and complex biographical work to make sense of and cope
      with illness. Self-management education programmes should take closer account of
      over-arching storylines that pattern experience of chronic illness and recognize
      that some elements of self-management knowledge cannot be pre-specified in a
      structured curriculum.

PMID- 20819915
TI  - Local antibiotic delivery with bovine cancellous chips.
AB  - Infected bone defects and osteomyelitis are encountered frequently in trauma
      cases. Currently, the standard of care for osteomyelitis cases is prolonged
      systemic antibiotic therapy and implantation of antibiotic carrier beads.
      However, this method requires a secondary surgery to remove the beads after the
      infection has cleared. In the present study a common bone void filler was
      investigated for its ability to be infused with an antibiotic. This study
      demonstrates that the xenograft material tested can be loaded with gentamicin and
      release clinically relevant levels of the drug for at least 14 days in vitro
      allowing for the inhibition of bacterial growth on the graft. This study also
      demonstrates that the levels of gentamicin released did not have an adverse
      effect on primary osteoblast cell proliferation or ability to generate alkaline
      phosphatase. This bone void filler may represent a viable alternative to current
      methods of local antibiotic delivery in orthopedic applications.

PMID- 20819916
TI  - Improvement of the cell-loading efficiency of biomaterials by inoculation with
      stem cell-based microspheres, in osteogenesis.
AB  - In critical-size bone defects, autologous or allogenic cells are required in
      addition to compatible biomaterials for the successful defect healing. State of
      the art inoculation methods of biomaterials are based on the application of cell
      suspensions to the biomaterial. However, only less amounts of cells can be
      applied and sufficient adhesion to the material is required. Therefore, it was
      investigated whether the advantages of stem cell-based microspheres and insoluble
      collagenous bone matrix (ICBM) scaffolds can be combined which can lead to an
      advancement in cell seeding on biomaterials. Microspheres were produced from
      unrestricted somatic stem cells from human umbilical cord blood and were mounted
      on ICBM scaffolds. Following the incubation with osteogenic or control medium,
      the constructs were analyzed histologically after 3, 7, 14, and 28 days. Alizarin
      Red S and von Kossa staining revealed microsphere mineralization after 3 days in
      osteogenic and after 14 days in control medium. Meanwhile, a time-dependent
      increase in tissue, growing out of the microspheres, was detected. Our results
      provide evidence that microsphere-ICBM constructs are promising candidates for
      approaches of bone regeneration. They allow the transfer of substantially high
      numbers of cells in partially mineralized constructs.

PMID- 20819917
TI  - Sol-gel phosphate-based glass for drug delivery applications.
AB  - Development of controlled, targeted drug delivery systems represents one of the
      frontier areas of biomaterials science, where a multidisciplinary approach is of
      direct benefit to human healthcare. We demonstrate herein the potential of sol
      gel derived phosphate-based glass for use in drug delivery applications. Our low
      temperature sol-gel synthesis of phosphate-based glasses has made it possible to
      incorporate relatively unstable functional molecules for controlled release. We
      demonstrate the potential of this approach by incorporating the chemotherapy
      agent cisplatin in a CaO-Na(2)O-P(2)O(5) glass. X-ray absorption spectroscopy is
      used to show that the chlorine ligands of cisplatin undergo exchange with oxygen
      during the synthesis, consistent with binding to the phosphate groups of the sol
      gel. UV-visible spectroscopy reveals the subsequent release of cisplatin into an
      aqueous medium.

PMID- 20819918
TI  - Investigation of platelet responses and clotting characteristics of in situ
      albumin binding surfaces.
AB  - The response of biomaterial surfaces when exposed to blood is in part dependent
      upon the nature and composition of the adsorbed layer of proteins. Surfaces
      passivated with albumin have been shown to reduce platelet adhesion and
      activation. In an attempt to develop surfaces that can selectively and
      specifically bind albumin, silicon-based surfaces were functionalized with linear
      peptides and chemical ligands that displayed an affinity for albumin. Peptide
      functionalized surfaces were observed to preferentially bind albumin when
      compared to human immunoglobulin and human fibrinogen, which possess low
      densities of surface adsorbed platelets. The platelet morphology was noted to be
      discoid on the peptide modified surface. Both the unmodified control and SCL
      functionalized surfaces had high densities of surface adhered platelets with
      spread out morphology. The peptide and SCL functionalized surfaces were noted to
      have no impact on PTT and PT clotting times, indicating that the extrinsic and
      intrinsic pathways were unperturbed by the surfaces generated.

PMID- 20819919
TI  - Biosynthesis of calcium hydroxylapatite coating on sputtered Ti/TiN nano
      multilayers and their corrosion behavior in simulated body solution.
AB  - Titanium/titanium nitride (Ti/TiN) nanoscale multilayered films were deposited
      onto 316L stainless steel substrates by reactive magnetron sputtering using a Ti
      target. Coatings characterized by X-ray diffraction showed that the stack
      possesses centered cubic structure. The X-ray photoelectron spectroscopy survey
      spectra on the etched surfaces of the stack film on steel exhibited the
      characteristic Ti2p, N1s, and O1s peaks at the corresponding binding energies
      454.5, 397.0, and 530.6 eV, respectively. Platelet adhesion experiments were
      carried out to examine the interaction between blood and the materials in vitro.
      The results indicated that the smoothness and lower isoelectric point contribute
      to better hemocompatibility of the Ti/TiN nanoscale multilayered coating. The
      biomediated synthesis of calcium hydroxylapatite (HA) was carried out on coated
      substrates using calcium-depositing bacteria. The observation of low corrosion
      current density (I(corr)) for the calcium HA-coated Ti/TiN specimens in simulated
      body fluid confirmed their highly resistive nature under the testing condition.

PMID- 20819920
TI  - Cytotoxicity of gold nanoparticles prepared by ultrasonic spray pyrolysis.
AB  - The aim of this work was to study the cytotoxicity of different fractions of gold
      nanoparticles prepared by ultrasonic spray pyrolysis from gold scrap. The target
      cells were rat thymocytes, as a type of nonproliferating cells, and L929 mouse
      fibroblasts, as a type of continuous proliferating cells. Fractions 1 and 2,
      composed of pure gold nanoparticles, as determined by scanning electron
      microscopy with a combination of energy dispersive X-ray analysis, were nontoxic
      for thymocytes, but reduced moderately the proliferative activity of L929 cells.
      The inhibitory effect of fraction 2, containing particles smaller in size than
      fraction 1, was stronger. Fraction 3, composed of Au and up to 3% Cu was
      noncytotoxic for thymocytes, but was cytotoxic for L929 cells. Fraction 4,
      composed of Au and Ag nanoparticles, and fraction 5, composed of Au together with
      Cu, Ni, Zn, Fe, and In were cytotoxic for both thymocytes and L929 cells. These
      results suggest that USP enables the synthesis of pure gold nanoparticles with
      controlled size, even from gold scrap. However, microstructural analyses and
      biocompatibility testing are necessary for their proper selection from more
      cytotoxic gold nanoparticles, contaminated with other elements of gold alloys.

PMID- 20819921
TI  - Biomechanical characterization of an osteoporotic artificial bone model for the
      distal femur.
AB  - The treatment of osteoporotic distal femur fractures is still an unsolved problem
      of trauma surgery. The poor bone stock often leads to secondary loss of reduction
      and implant failure. Therefore, the development of new implants and their
      biomechanical testing is essential. In a previous study, we developed and
      initially characterized an artificial osteoporotic bone model of the distal
      femur. This follow-up study was performed to characterize this model in a
      biomechanical comparison. We investigated two different artificial bones: five
      foam cortical shell (Sawbones) and 10 custom-made artificial femoral condyles.
      Additionally, eight human femora were used for comparison. For biomechanical
      testing, two intramedullary nails (distal femur nail (DFN) and supracondylar nail
      (SCN)) were cyclically axial loaded in an AO 33 C2 unstable distal femoral
      fracture model. In our testing, the artificial bone showed a decrease in the
      axial stiffness of 27% for the SCN and 28% for the DFN compared to the human
      results. Also the number of cycles for a deformation of 2.5 mm was reduced by 55%
      (SCN) and 62% (DFN). This decrease was homogenous and caused by the relative high
      bone mineral density of the human specimen used. The modes of failure showed no
      difference between the artificial and human bones. Our customized artificial bone
      provides suitable results. In relation to the human bones classified as mildly
      osteoporotic, we assume that the biomechanical properties match to serve as an
      osteoporotic bone. Yet, we suggest to check transferability of the results with
      human material.

PMID- 20819922
TI  - Mechanical properties and drug release behavior of bioactivated PMMA cements.
AB  - Septic loosening of cemented implants represents an unresolved long-term problem
      of total hip endoprostheses. Common treatments of infected prostheses involve the
      use of temporary antibiotic-loaded PMMA spacer-implants or antibiotic-loaded
      cements. The latter are either provided by a manufacturer or are obtained by
      simply mixing specific antibiotic powders according to a microbial sensitivity
      test with PMMA cement. This study is aimed to investigate the antibiotic release
      behavior and mechanical properties of novel modified PMMA cements, which were
      bioactivated by chemical modification of commercial cements with either 0.5%
      hydroxyethylmethacrylate-phosphate (HEMA-P) or 0.5% hydroxyethylmethacrylate
      phosphate + calcium chloride and sodium carbonate as buffer. Tobramycin release
      experiments from the cements were performed statically by immersion of the drug
      loaded samples in PBS buffer following liquid change after different periods of
      time or during cyclic mechanical loading of the cement samples. Cement
      modification did not significantly alter the mechanical properties of the
      cements, but affected the release rate from the matrix. While the unmodified
      cement released approximately 0.33 mg/cm(2) tobramycin after 48 h independent of
      the testing regime, modification with both HEMA-P and salt buffer increased the
      antibiotic release to 37-50 mg/cm(2) when tested under cyclical mechanical
      loading.

PMID- 20819923
TI  - Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen
      specific CD8+ T cell dysfunction in melanoma patients.
AB  - The paradoxical coexistence of spontaneous tumor antigen-specific immune
      responses with progressive disease in cancer patients furthers the need to
      dissect the molecular pathways involved in tumor-induced T cell dysfunction. In
      patients with advanced melanoma, we have previously shown that the cancer
      germline antigen NY-ESO-1 stimulates spontaneous NY-ESO-1-specific CD8(+) T cells
      that up-regulate PD-1 expression. We also observed that PD-1 regulates NY-ESO-1
      specific CD8(+) T cell expansion upon chronic antigen stimulation. In the present
      study, we show that a fraction of PD-1(+) NY-ESO-1-specific CD8(+) T cells in
      patients with advanced melanoma up-regulates Tim-3 expression and that Tim-3(+)PD
      1(+) NY-ESO-1-specific CD8(+) T cells are more dysfunctional than Tim-3(-)PD-1(+)
      and Tim-3(-)PD-1(-) NY-ESO-1-specific CD8(+) T cells, producing less IFN-gamma,
      TNF, and IL-2. Tim-3-Tim-3L blockade enhanced cytokine production by NY-ESO-1
      specific CD8(+) T cells upon short ex vivo stimulation with cognate peptide, thus
      enhancing their functional capacity. In addition, Tim-3-Tim-3L blockade enhanced
      cytokine production and proliferation of NY-ESO-1-specific CD8(+) T cells upon
      prolonged antigen stimulation and acted in synergy with PD-1-PD-L1 blockade.
      Collectively, our findings support the use of Tim-3-Tim-3L blockade together with
      PD-1-PD-L1 blockade to reverse tumor-induced T cell exhaustion/dysfunction in
      patients with advanced melanoma.

PMID- 20819924
TI  - MHC class I-deficient natural killer cells acquire a licensed phenotype after
      transfer into an MHC class I-sufficient environment.
AB  - In MHC class I-deficient hosts, natural killer (NK) cells are hyporesponsive to
      cross-linking of activation receptors. Functional competence requires engagement
      of a self-major histocompatability complex (MHC) class I-specific inhibitory
      receptor, a process referred to as "licensing." We previously suggested that
      licensing is developmentally determined in the bone marrow. In this study, we
      find that unlicensed mature MHC class I-deficient splenic NK cells show gain-of
      function and acquire a licensed phenotype after adoptive transfer into wild-type
      (WT) hosts. Transferred NK cells produce WT levels of interferon-gamma after
      engagement of multiple activation receptors, and degranulate at levels equivalent
      to WT NK cells upon coincubation with target cells. Only NK cells expressing an
      inhibitory Ly49 receptor specific for a cognate host MHC class I molecule show
      this gain-of-function. Therefore, these findings, which may be relevant to
      clinical bone marrow transplantation, suggest that neither exposure to MHC class
      I ligands during NK development in the BM nor endogenous MHC class I expression
      by NK cells themselves is absolutely required for licensing.

PMID- 20819925
TI  - Inflammatory dendritic cells--not basophils--are necessary and sufficient for
      induction of Th2 immunity to inhaled house dust mite allergen.
AB  - It is unclear how Th2 immunity is induced in response to allergens like house
      dust mite (HDM). Here, we show that HDM inhalation leads to the TLR4/MyD88
      dependent recruitment of IL-4 competent basophils and eosinophils, and of
      inflammatory DCs to the draining mediastinal nodes. Depletion of basophils only
      partially reduced Th2 immunity, and depletion of eosinophils had no effect on the
      Th2 response. Basophils did not take up inhaled antigen, present it to T cells,
      or express antigen presentation machinery, whereas a population of FceRI(+) DCs
      readily did. Inflammatory DCs were necessary and sufficient for induction of Th2
      immunity and features of asthma, whereas basophils were not required. We favor a
      model whereby DCs initiate and basophils amplify Th2 immunity to HDM allergen.

PMID- 20819926
TI  - CD11c depletion severely disrupts Th2 induction and development in vivo.
AB  - Although dendritic cells (DCs) are adept initiators of CD4(+) T cell responses,
      their fundamental importance in this regard in Th2 settings remains to be
      demonstrated. We have used CD11c-diphtheria toxin (DTx) receptor mice to deplete
      CD11c(+) cells during the priming stage of the CD4(+) Th2 response against the
      parasitic helminth Schistosoma mansoni. DTx treatment significantly depleted
      CD11c(+) DCs from all tissues tested, with 70-80% efficacy. Even this incomplete
      depletion resulted in dramatically impaired CD4(+) T cell production of Th2
      cytokines, altering the balance of the immune response and causing a shift toward
      IFN-gamma production. In contrast, basophil depletion using Mar-1 antibody had no
      measurable effect on Th2 induction in this system. These data underline the vital
      role that CD11c(+) antigen-presenting cells can play in orchestrating Th2
      development against helminth infection in vivo, a response that is ordinarily
      balanced so as to prevent the potentially damaging production of inflammatory
      cytokines.

PMID- 20819927
TI  - Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti
      tumor immunity.
AB  - The immune response plays an important role in staving off cancer; however,
      mechanisms of immunosuppression hinder productive anti-tumor immunity. T cell
      dysfunction or exhaustion in tumor-bearing hosts is one such mechanism. PD-1 has
      been identified as a marker of exhausted T cells in chronic disease states, and
      blockade of PD-1-PD-1L interactions has been shown to partially restore T cell
      function. We have found that T cell immunoglobulin mucin (Tim) 3 is expressed on
      CD8(+) tumor-infiltrating lymphocytes (TILs) in mice bearing solid tumors. All
      Tim-3(+) TILs coexpress PD-1, and Tim-3(+)PD-1(+) TILs represent the predominant
      fraction of T cells infiltrating tumors. Tim-3(+)PD-1(+) TILs exhibit the most
      severe exhausted phenotype as defined by failure to proliferate and produce IL-2,
      TNF, and IFN-gamma. We further find that combined targeting of the Tim-3 and PD-1
      pathways is more effective in controlling tumor growth than targeting either
      pathway alone.

PMID- 20819928
TI  - Mature natural killer cells reset their responsiveness when exposed to an altered
      MHC environment.
AB  - Some mature natural killer (NK) cells cannot be inhibited by major
      histocompatibility complex (MHC) I molecules, either because they lack
      corresponding inhibitory receptors or because the host lacks the corresponding
      MHC I ligands for the receptors. Such NK cells nevertheless remain self-tolerant
      and exhibit a generalized hyporesponsiveness to stimulation through activating
      receptors. To address whether NK cell responsiveness is set only during the NK
      cell differentiation process, we transferred mature NK cells from wild-type (WT)
      to MHC I-deficient hosts or vice versa. Remarkably, mature responsive NK cells
      from WT mice became hyporesponsive after transfer to MHC I-deficient mice,
      whereas mature hyporesponsive NK cells from MHC I-deficient mice became
      responsive after transfer to WT mice. Altered responsiveness was evident among
      mature NK cells that had not divided in the recipient animals, indicating that
      the cells were mature before transfer and that alterations in activity did not
      require cell division. Furthermore, the percentages of NK cells expressing KLRG1,
      CD11b, CD27, and Ly49 receptors specific for H-2(b) were not markedly altered
      after transfer. Thus, the functional activity of mature NK cells can be reset
      when the cells are exposed to a changed MHC environment. These findings have
      important implications for how NK cell functions may be curtailed or enhanced in
      the context of disease.

PMID- 20819929
TI  - Monica Bettencourt-Dias: centered on centrioles. Interview by Ben Short.

PMID- 20819931
TI  - NPHP proteins: gatekeepers of the ciliary compartment.
AB  - The cilia and the cytoplasm are separated by a region called the transition zone,
      where wedge-shaped structures link the microtubule doublets of the axoneme to the
      ciliary membrane, thereby forming a ciliary "gate." In this issue, Craige et al.
      (J. Cell Biol. doi:10.1083/jcb.201006105) demonstrate in Chlamydomonas
      reinhardtii that Nphp6/cep290, which is mutated in nephronophthisis (NPHP), is an
      integral component of these connectors and maintains the structural integrity of
      this gate.

PMID- 20819933
TI  - Formation of a Bazooka-Stardust complex is essential for plasma membrane polarity
      in epithelia.
AB  - Apical-basal polarity in Drosophila melanogaster epithelia depends on several
      evolutionarily conserved proteins that have been assigned to two distinct protein
      complexes: the Bazooka (Baz)-PAR-6 (partitioning defective 6)-atypical protein
      kinase C (aPKC) complex and the Crumbs (Crb)-Stardust (Sdt) complex. These
      proteins operate in a functional hierarchy, in which Baz is required for the
      proper subcellular localization of all other proteins. We investigated how these
      proteins interact and how this interaction is regulated. We show that Baz
      recruits Sdt to the plasma membrane by direct interaction between the
      Postsynaptic density 95/Discs large/Zonula occludens 1 (PDZ) domain of Sdt and a
      region of Baz that contains a phosphorylation site for aPKC. Phosphorylation of
      Baz causes the dissociation of the Baz-Sdt complex. Overexpression of a
      nonphosphorylatable version of Baz blocks the dissociation of Sdt from Baz,
      causing phenotypes very similar to those of crb and sdt mutations. Our findings
      provide a molecular mechanism for the phosphorylation-dependent interaction
      between the Baz-PAR-3 and Crb complexes during the establishment of epithelial
      polarity.

PMID- 20819932
TI  - Protein homeostasis and aging in neurodegeneration.
AB  - Genetic and environmental factors responsible for numerous neurodegenerative
      diseases vary between disorders, yet age remains a universal risk factor. Age
      associated decline in protein homeostasis, or proteostasis, enables disease
      linked proteins to adopt aberrant tertiary structures, accumulate as higher
      ordered aggregates, and cause a myriad of cellular dysfunctions and neuronal
      death. However, recent findings suggest that the assembly of disease proteins
      into tightly ordered aggregates can significantly delay proteotoxic onset.
      Furthermore, manipulation of metabolic pathways through key signaling components
      extends lifespan, bolsters proteostasis networks, and delays the onset of
      proteotoxicity. Thus, understanding the relationship between proteostasis and
      aging has provided important insights into neurodegeneration.

PMID- 20819934
TI  - Dynamic plasticity of large-scale chromatin structure revealed by self-assembly
      of engineered chromosome regions.
AB  - Interphase chromatin compaction well above the 30-nm fiber is well documented,
      but the structural motifs underlying this level of chromatin folding remain
      unknown. Taking a reductionist approach, we analyzed in mouse embryonic stem (ES)
      cells and ES-derived fibroblasts and erythroblasts the folding of 10-160-megabase
      pair engineered chromosome regions consisting of tandem repeats of bacterial
      artificial chromosomes (BACs) containing approximately 200 kilobases of mammalian
      genomic DNA tagged with lac operator (LacO) arrays. Unexpectedly, linear mitotic
      and interphase chromatid regions formed from noncontiguously folded DNA
      topologies. Particularly, in ES cells, these model chromosome regions self
      organized with distant sequences segregating into functionally distinct, compact
      domains. Transcriptionally active and histone H3K27me3-modified regions
      positioned toward the engineered chromosome subterritory exterior, with LacO
      repeats and the BAC vector backbone localizing within an H3K9me3, HP1-enriched
      core. Differential compaction of Dhfr and alpha- and beta-globin transgenes was
      superimposed on dramatic, lineage-specific reorganization of large-scale
      chromatin folding, demonstrating a surprising plasticity of large-scale chromatin
      organization.

PMID- 20819935
TI  - Identification and characterization of two novel primate-specific histone H3
      variants, H3.X and H3.Y.
AB  - Nucleosomal incorporation of specialized histone variants is an important
      mechanism to generate different functional chromatin states. Here, we describe
      the identification and characterization of two novel primate-specific histone H3
      variants, H3.X and H3.Y. Their messenger RNAs are found in certain human cell
      lines, in addition to several normal and malignant human tissues. In keeping with
      their primate specificity, H3.X and H3.Y are detected in different brain regions.
      Transgenic H3.X and H3.Y proteins are stably incorporated into chromatin in a
      similar fashion to the known H3 variants. Importantly, we demonstrate
      biochemically and by mass spectrometry that endogenous H3.Y protein exists in
      vivo, and that stress stimuli, such as starvation and cellular density, increase
      the abundance of H3.Y-expressing cells. Global transcriptome analysis revealed
      that knockdown of H3.Y affects cell growth and leads to changes in the expression
      of many genes involved in cell cycle control. Thus, H3.Y is a novel histone
      variant involved in the regulation of cellular responses to outside stimuli.

PMID- 20819936
TI  - Molecular architecture and assembly of the yeast kinetochore MIND complex.
AB  - The MIND multiprotein complex is a conserved, essential component of eukaryotic
      kinetochores and is a constituent of the tripartite KMN network that directly
      attaches the kinetochore to the mitotic spindle. The primary microtubule-binding
      complex in this network, NDC80, has been extensively characterized, but very
      little is known about the structure or function of the MIND complex. In this
      study, we present biochemical, hydrodynamic, electron microscopy, and small-angle
      x-ray scattering data that provide insight into the overall architecture and
      assembly of the MIND complex and the physical relationship of the complex with
      other components of the KMN network. We propose a model for the overall structure
      of the complex and provide data on the interactions with NDC80, Spc105p, and thus
      the mitotic spindle.

PMID- 20819937
TI  - The MIS12 complex is a protein interaction hub for outer kinetochore assembly.
AB  - Kinetochores are nucleoprotein assemblies responsible for the attachment of
      chromosomes to spindle microtubules during mitosis. The KMN network, a crucial
      constituent of the outer kinetochore, creates an interface that connects
      microtubules to centromeric chromatin. The NDC80, MIS12, and KNL1 complexes form
      the core of the KMN network. We recently reported the structural organization of
      the human NDC80 complex. In this study, we extend our analysis to the human MIS12
      complex and show that it has an elongated structure with a long axis of
      approximately 22 nm. Through biochemical analysis, cross-linking-based methods,
      and negative-stain electron microscopy, we investigated the reciprocal
      organization of the subunits of the MIS12 complex and their contacts with the
      rest of the KMN network. A highlight of our findings is the identification of the
      NSL1 subunit as a scaffold supporting interactions of the MIS12 complex with the
      NDC80 and KNL1 complexes. Our analysis has important implications for
      understanding kinetochore organization in different organisms.

PMID- 20819938
TI  - Functional dichotomy of ribosomal proteins during the synthesis of mammalian 40S
      ribosomal subunits.
AB  - Our knowledge of the functions of metazoan ribosomal proteins in ribosome
      synthesis remains fragmentary. Using siRNAs, we show that knockdown of 31 of the
      32 ribosomal proteins of the human 40S subunit (ribosomal protein of the small
      subunit [RPS]) strongly affects pre-ribosomal RNA (rRNA) processing, which often
      correlates with nucleolar chromatin disorganization. 16 RPSs are strictly
      required for initiating processing of the sequences flanking the 18S rRNA in the
      pre-rRNA except at the metazoan-specific early cleavage site. The remaining 16
      proteins are necessary for progression of the nuclear and cytoplasmic maturation
      steps and for nuclear export. Distribution of these two subsets of RPSs in the
      40S subunit structure argues for a tight dependence of pre-rRNA processing
      initiation on the folding of both the body and the head of the forming subunit.
      Interestingly, the functional dichotomy of RPS proteins reported in this study is
      correlated with the mutation frequency of RPS genes in Diamond-Blackfan anemia.

PMID- 20819939
TI  - microRNA-1 and microRNA-206 regulate skeletal muscle satellite cell proliferation
      and differentiation by repressing Pax7.
AB  - Skeletal muscle satellite cells are adult stem cells responsible for postnatal
      skeletal muscle growth and regeneration. Paired-box transcription factor Pax7
      plays a central role in satellite cell survival, self-renewal, and proliferation.
      However, how Pax7 is regulated during the transition from proliferating satellite
      cells to differentiating myogenic progenitor cells is largely unknown. In this
      study, we find that miR-1 and miR-206 are sharply up-regulated during satellite
      cell differentiation and down-regulated after muscle injury. We show that miR-1
      and miR-206 facilitate satellite cell differentiation by restricting their
      proliferative potential. We identify Pax7 as one of the direct regulatory targets
      of miR-1 and miR-206. Inhibition of miR-1 and miR-206 substantially enhances
      satellite cell proliferation and increases Pax7 protein level in vivo.
      Conversely, sustained Pax7 expression as a result of the loss of miR-1 and miR
      206 repression elements at its 3' untranslated region significantly inhibits
      myoblast differentiation. Therefore, our experiments suggest that microRNAs
      participate in a regulatory circuit that allows rapid gene program transitions
      from proliferation to differentiation.

PMID- 20819940
TI  - Endogenous HMGB1 regulates autophagy.
AB  - Autophagy clears long-lived proteins and dysfunctional organelles and generates
      substrates for adenosine triphosphate production during periods of starvation and
      other types of cellular stress. Here we show that high mobility group box 1
      (HMGB1), a chromatin-associated nuclear protein and extracellular damage
      associated molecular pattern molecule, is a critical regulator of autophagy.
      Stimuli that enhance reactive oxygen species promote cytosolic translocation of
      HMGB1 and thereby enhance autophagic flux. HMGB1 directly interacts with the
      autophagy protein Beclin1 displacing Bcl-2. Mutation of cysteine 106 (C106), but
      not the vicinal C23 and C45, of HMGB1 promotes cytosolic localization and
      sustained autophagy. Pharmacological inhibition of HMGB1 cytoplasmic
      translocation by agents such as ethyl pyruvate limits starvation-induced
      autophagy. Moreover, the intramolecular disulfide bridge (C23/45) of HMGB1 is
      required for binding to Beclin1 and sustaining autophagy. Thus, endogenous HMGB1
      is a critical pro-autophagic protein that enhances cell survival and limits
      programmed apoptotic cell death.

PMID- 20819942
TI  - Complementary spatial firing in place cell-interneuron pairs.
AB  - The hippocampal formation plays a pivotal role in representing the physical
      environment. While CA1 pyramidal cells display sharply tuned location-specific
      firing, the activity of many interneurons show weaker but significant spatial
      modulation. Although hippocampal interneurons were proposed to participate in the
      representation of space, their interplay with pyramidal cells in formation of
      spatial maps is not well understood. In this study, we investigated the spatial
      correlation between CA1 pyramidal cells and putative interneurons recorded
      concurrently in awake rats. Positively and negatively correlated pairs were found
      to be simultaneously present in the CA1 region. While pyramidal cell-interneuron
      pairs with positive spatial correlation showed similar firing maps, negative
      spatial correlation was often accompanied by complementary place maps, which
      could occur even in the presence of a monosynaptic excitation between the cells.
      Thus, location-specific firing increase of hippocampal interneurons is not
      necessarily a simple product of excitation by a pyramidal cell with a similarly
      positioned firing field. Based on our observation of pyramidal cells firing
      selectively in the low firing regions of interneurons, we speculate that the
      location-specific firing of place cells is partly determined by the location
      specific decrease of interneuron activity that can release place cells from
      inhibition.

PMID- 20819941
TI  - CEP290 tethers flagellar transition zone microtubules to the membrane and
      regulates flagellar protein content.
AB  - Mutations in human CEP290 cause cilia-related disorders that range in severity
      from isolated blindness to perinatal lethality. Here, we describe a Chlamydomonas
      reinhardtii mutant in which most of the CEP290 gene is deleted. Immunoelectron
      microscopy indicated that CEP290 is located in the flagellar transition zone in
      close association with the prominent microtubule-membrane links there.
      Ultrastructural analysis revealed defects in these microtubule-membrane
      connectors, resulting in loss of attachment of the flagellar membrane to the
      transition zone microtubules. Biochemical analysis of isolated flagella revealed
      that the mutant flagella have abnormal protein content, including abnormal levels
      of intraflagellar transport proteins and proteins associated with ciliopathies.
      Experiments with dikaryons showed that CEP290 at the transition zone is dynamic
      and undergoes rapid turnover. The results indicate that CEP290 is required to
      form microtubule-membrane linkers that tether the flagellar membrane to the
      transition zone microtubules, and is essential for controlling flagellar protein
      composition.

PMID- 20819943
TI  - Light increases the gap junctional coupling of retinal ganglion cells.
AB  - We examined the effect of light adaptation on the gap junctional coupling of
      alpha-ganglion cells (alpha-GCs) in rabbit and mouse retinas. We assayed changes
      in coupling by measuring parameters of tracer coupling following injection of
      alpha-GCs with Neurobiotin and the concerted spike activity of alpha-GC
      neighbours under dark- and light-adapted conditions. We found that light
      adaptation using mesopic or photopic background lights resulted in a dramatic
      increase in the labelling intensity, number, and spatial extent of ganglion and
      amacrine cells coupled to OFF alpha-GCs when compared to levels seen under dark
      adaptation. While this augmentation of coupling by light did not produce an
      increase in the concerted spontaneous activity of OFF alpha-GC neighbours, it did
      significantly increase correlated light-evoked spiking. This was seen as an
      increase in the number of correlated spikes for alpha-GC neighbours and an
      extension of correlations to second-tier neighbours that was not seen under dark
      adapted conditions. Pharmacological studies in the rabbit retina indicated that
      dopamine mediates the observed changes in coupling by differentially activating
      D1 and D2 receptors under different adaptation states. In this scheme, activation
      of dopamine D1 receptors following light exposure triggers cAMP-mediated
      intracellular pathways resulting in an increase in gap junctional conductance.
      Overall, our results indicate that as we move from night to day there is an
      enhanced electrical coupling between alpha-GCs, thereby increasing the concerted
      activity believed to strengthen the capacity and efficiency of information flow
      across the optic nerve.

PMID- 20819945
TI  - Involvement of the cystic fibrosis transmembrane conductance regulator in the
      acidosis-induced efflux of ATP from rat skeletal muscle.
AB  - The present study was performed to investigate the effect of acidosis on the
      efflux of ATP from skeletal muscle. Infusion of lactic acid to the perfused
      hindlimb muscles of anaesthetised rats produced dose-dependent decreases in pH
      and increases in the interstitial ATP of extensor digitorum longus (EDL) muscle:
      10 mM lactic acid reduced the venous pH from 7.22 +/- 0.04 to 6.97 +/- 0.02 and
      increased interstitial ATP from 38 +/- 8 to 67 +/- 11 nM. The increase in
      interstitial ATP was well-correlated with the decrease in pH (r(2) = 0.93; P <
      0.05). Blockade of cellular uptake of lactic acid using alpha-cyano
      hydroxycinnamic acid abolished the lactic acid-induced ATP release, whilst
      infusion of sodium lactate failed to depress pH or increase interstitial ATP,
      suggesting that intracellular pH depression, rather than lactate, stimulated the
      ATP efflux. Incubation of cultured skeletal myoblasts with 10 mM lactic acid
      significantly increased the accumulation of ATP in the bathing medium from 0.46
      +/- 0.06 to 0.76 +/- 0.08 MUM, confirming the skeletal muscle cells as the source
      of the released ATP. Acidosis-induced ATP efflux from the perfused muscle was
      abolished by CFTR(inh)-172, a specific inhibitor of the cystic fibrosis
      transmembrane conductance regulator (CFTR), or glibenclamide, an inhibitor of
      both K(ATP) channels and CFTR, but it was not affected by atractyloside, an
      inhibitor of the mitochondrial ATP transporter. Silencing of the CFTR gene using
      an siRNA abolished the acidosis-induced increase in ATP release from cultured
      myoblasts. CFTR expression on skeletal muscle cells was confirmed using
      immunostaining in the intact muscle and Western blotting in the cultured cells.
      These data suggest that depression of the intracellular pH of skeletal muscle
      cells stimulates ATP efflux, and that CFTR plays an important role in the release
      mechanism.

PMID- 20819946
TI  - Differential effects of Na+-K+ ATPase blockade on cortical layer V neurons.
AB  - Sodium-potassium ATPase ('Na(+)-K(+) ATPase') contributes to the maintenance of
      the resting membrane potential and the transmembrane gradients for Na(+) and K(+)
      in neurons. Activation of Na(+)-K(+) ATPase may be important in controlling
      increases in intracellular sodium during periods of increased neuronal activity.
      Down-regulation of Na(+)-K(+) ATPase activity is implicated in numerous CNS
      disorders, including epilepsy. Although Na(+)-K(+) ATPase is present in all
      neurons, little is known about its activity in different subclasses of
      neocortical cells. We assessed the physiological properties of Na(+)-K(+) ATPase
      in fast-spiking (FS) interneurons and pyramidal (PYR) cells to test the
      hypothesis that Na(+)-K(+) ATPase activity would be relatively greater in neurons
      that generated high frequency action potentials (the FS cells). Whole-cell patch
      clamp recordings were made from FS and PYR neurons in layer V of rat sensorimotor
      cortical slices maintained in vitro using standard techniques. Bath perfusion of
      Na(+)-K(+) ATPase antagonists (ouabain or dihydro-ouabain) induced either a
      membrane depolarization in current clamp, or inward current under voltage clamp
      in both cell types. PYR neurons were divided into two subpopulations based on the
      amplitude of the voltage or current shift in response to Na(+)-K(+) ATPase
      blockade. The two PYR cell groups did not differ significantly in
      electrophysiological properties including resting membrane potential, firing
      pattern, input resistance and capacitance. Membrane voltage responses of FS cells
      to Na(+)-K(+) ATPase blockade were intermediate between the two PYR cell groups
      (P < 0.05). The resting Na(+)-K(+) ATPase current density in FS interneurons,
      assessed by application of blockers, was 3- to 7-fold larger than in either group
      of PYR neurons. Na(+)-K(+) ATPase activity was increased either through direct
      Na(+) loading via the patch pipette or by focal application of glutamate (20 mM
      puffs). Under these conditions FS interneurons exhibited the largest increase in
      Na(+)-K(+) ATPase activity. We conclude that resting Na(+)-K(+) ATPase activity
      and sensitivity to changes in internal Na(+) concentration vary between and
      within classes of cortical neurons. These differences may have important
      consequences in pathophysiological disorders associated with down-regulation of
      Na(+)-K(+) ATPase and hyperexcitability within cortical networks.

PMID- 20819947
TI  - Cotransport of water by the Na+-K+-2Cl(-) cotransporter NKCC1 in mammalian
      epithelial cells.
AB  - Water transport by the Na+-K+-2Cl(-) cotransporter (NKCC1) was studied in
      confluent cultures of pigmented epithelial (PE) cells from the ciliary body of
      the fetal human eye. Interdependence among water, Na+ and Cl(-) fluxes mediated
      by NKCC1 was inferred from changes in cell water volume, monitored by
      intracellular self-quenching of the fluorescent dye calcein. Isosmotic removal of
      external Cl(-) or Na+ caused a rapid efflux of water from the cells, which was
      inhibited by bumetanide (10 MUm). When returned to the control solution there was
      a rapid water influx that required the simultaneous presence of external Na+ and
      Cl(-). The water influx could proceed uphill, against a transmembrane osmotic
      gradient, suggesting that energy contained in the ion fluxes can be transferred
      to the water flux. The influx of water induced by changes in external [Cl(-)]
      saturated in a sigmoidal fashion with a Km of 60 mm, while that induced by
      changes in external [Na+] followed first order kinetics with a Km of about 40 mm.
      These parameters are consistent with ion transport mediated by NKCC1. Our
      findings support a previous investigation, in which we showed water transport by
      NKCC1 to be a result of a balance between ionic and osmotic gradients. The
      coupling between salt and water transport in NKCC1 represents a novel aspect of
      cellular water homeostasis where cells can change their volume independently of
      the direction of an osmotic gradient across the membrane. This has relevance for
      both epithelial and symmetrical cells.

PMID- 20819948
TI  - Suppressor of cytokine signaling 3 knockdown in the mediobasal hypothalamus:
      counterintuitive effects on energy balance.
AB  - An increase in brain suppressor of cytokine signaling 3 (SOCS3) has been
      implicated in the development of both leptin and insulin resistance. Socs3 mRNA
      is localized throughout the brain, and it remains unclear which brain areas are
      involved in the effect of SOCS3 levels on energy balance. We investigated the
      role of SOCS3 expressed in the mediobasal hypothalamus (MBH) in the development
      of diet-induced obesity in adult rats. Socs3 mRNA was down-regulated by local
      injection of adeno-associated viral vectors expressing a short hairpin directed
      against Socs3, after which we determined the response to high-fat high-sucrose
      choice diet. In contrast to neuronal Socs3 knockout mice, rats with SOCS3
      knockdown limited to the MBH showed increased body weight gain, larger amounts of
      white adipose tissue, and higher leptin concentrations at the end of the
      experiment. These effects were partly due to the decrease in locomotor activity,
      as 24 h food intake was comparable with controls. In addition, rats with Socs3
      knockdown in the MBH showed alterations in their meal patterns: average meal size
      in the light period was increased and was accompanied by a compensatory decrease
      in meal frequency in the dark phase. In addition, neuropeptide Y (Npy) mRNA
      levels were significantly increased in the arcuate nucleus of Socs3 knockdown
      rats. Since leptin is known to stimulate Npy transcription in the absence of
      Socs3, these data suggest that knockdown of Socs3 mRNA limited to the MBH
      increases Npy mRNA levels, which subsequently decreases locomotor activity and
      alters feeding patterns.

PMID- 20819949
TI  - Knockdown of zebrafish Lgi1a results in abnormal development, brain defects and a
      seizure-like behavioral phenotype.
AB  - Epilepsy is a common disorder, typified by recurrent seizures with underlying
      neurological disorders or disease. Approximately one-third of patients are
      unresponsive to currently available therapies. Thus, a deeper understanding of
      the genetics and etiology of epilepsy is needed to advance the development of new
      therapies. Previously, treatment of zebrafish with epilepsy-inducing
      pharmacological agents was shown to result in a seizure-like phenotype,
      suggesting that fish provide a tractable model to understand the function of
      epilepsy-predisposing genes. Here, we report the first model of genetically
      linked epilepsy in zebrafish and provide an initial characterization of the
      behavioral and neurological phenotypes associated with morpholino (MO) knockdown
      of leucine-rich, glioma-inactivated 1a (lgi1a) expression. Mutations in the LGI1
      gene in humans have been shown to predispose to a subtype of autosomal dominant
      epilepsy. Low-dose Lgi1a MO knockdown fish (morphants) appear morphologically
      normal but are sensitized to epilepsy-inducing drugs. High-dose Lgi1a morphants
      have morphological defects which persist into adult stages that are typified by
      smaller brains and eyes and abnormalities in tail shape, and display hyperactive
      swimming behaviors. Increased apoptosis was observed throughout the central
      nervous system of high-dose morphant fish, accounting for the size reduction of
      neural tissues. These observations demonstrate that zebrafish can be exploited to
      dissect the embryonic function(s) of genes known to predispose to seizure-like
      behavior in humans, and offer potential insight into the relationship between
      developmental neurobiological abnormalities and seizure.

PMID- 20819950
TI  - Angiotensin II blockade: a strategy to slow ageing by protecting mitochondria?
AB  - Protein and lipid oxidation-mainly by mitochondrial reactive oxygen species
      (mtROS)-was proposed as a crucial determinant of health and lifespan. Angiotensin
      II (Ang II) enhances ROS production by activating NAD(P)H oxidase and uncoupling
      endothelial nitric oxide synthase (NOS). Ang II also stimulates mtROS production,
      which depresses mitochondrial energy metabolism. In rodents, renin-angiotensin
      system blockade (RAS blockade) increases survival and prevents age-associated
      changes. RAS blockade reduces mtROS and enhances mitochondrial content and
      function. This suggests that Ang II contributes to the ageing process by
      prompting mitochondrial dysfunction. Since Ang II is a pleiotropic peptide, the
      age-protecting effects of RAS blockade are expected to involve a variety of other
      mechanisms. Caloric restriction (CR)-an age-retarding intervention in humans and
      animals-and RAS blockade display a number of converging effects, i.e. they delay
      the manifestations of hypertension, diabetes, nephropathy, cardiovascular
      disease, and cancer; increase body temperature; reduce body weight, plasma
      glucose, insulin, and insulin-like growth factor-1; ameliorate insulin
      sensitivity; lower protein, lipid, and DNA oxidation, and mitochondrial H(2)O(2)
      production; and increase uncoupling protein-2 and sirtuin expression. A number of
      these overlapping effects involve changes in mitochondrial function. In CR,
      peroxisome proliferator-activated receptors (PPARs) seem to contribute to age
      retardation partly by regulating mitochondrial function. RAS inhibition up
      regulates PPARs; therefore, it is feasible that PPAR modulation is pivotal for
      mitochondrial protection by RAS blockade during rodent ageing. Other potential
      mechanisms that may underlie RAS blockade's mitochondrial benefits are TGF-beta
      down-regulation and up-regulation of Klotho and sirtuins. In conclusion, the
      available data suggest that RAS blockade deserves further research efforts to
      establish its role as a potential tool to mitigate the growing problem of age
      associated chronic disease.

PMID- 20819951
TI  - Liver cytochrome P450 3A ubiquitination in vivo by gp78/autocrine motility factor
      receptor and C terminus of Hsp70-interacting protein (CHIP) E3 ubiquitin ligases:
      physiological and pharmacological relevance.
AB  - CYP3A4 is a dominant human liver cytochrome P450 enzyme engaged in the metabolism
      and disposition of >50% of clinically relevant drugs and held responsible for
      many adverse drug-drug interactions. CYP3A4 and its mammalian liver CYP3A
      orthologs are endoplasmic reticulum (ER)-anchored monotopic proteins that undergo
      ubiquitin (Ub)-dependent proteasomal degradation (UPD) in an ER-associated
      degradation (ERAD) process. These integral ER proteins are ubiquitinated in vivo,
      and in vitro studies have identified the ER-integral gp78 and the cytosolic co
      chaperone, CHIP (C terminus of Hsp70-interacting protein), as the relevant E3 Ub
      ligases, along with their cognate E2 Ub-conjugating enzymes UBC7 and UbcH5a,
      respectively. Using lentiviral shRNA templates targeted against each of these Ub
      ligases, we now document that both E3s are indeed physiologically involved in
      CYP3A ERAD/UPD in cultured rat hepatocytes. Accordingly, specific RNAi resulted
      in ~80% knockdown of each hepatic Ub-ligase, with a corresponding ~2.5-fold CYP3A
      stabilization. Surprisingly, however, such stabilization resulted in increased
      levels of functionally active CYP3A, thereby challenging the previous notion that
      E3 recognition and subsequent ERAD of CYP3A proteins required ab initio their
      structural and/or functional inactivation. Furthermore, coexpression in HepG2
      cells of both CYP3A4 and gp78, but not its functionally inactive RING-finger
      mutant, resulted in enhanced CYP3A4 loss greater than that in corresponding cells
      expressing only CYP3A4. Stabilization of a functionally active CYP3A after RNAi
      knockdown of either of the E3s, coupled with the increased CYP3A4 loss on gp78 or
      CHIP coexpression, suggests that ERAD-associated E3 Ub-ligases can influence
      clinically relevant drug metabolism by effectively regulating the physiological
      CYP3A content and consequently its function.

PMID- 20819952
TI  - Forcing switch from short- to intermediate- and long-lived states of the alphaA
      domain generates LFA-1/ICAM-1 catch bonds.
AB  - Binding of lymphocyte function-associated antigen-1 (LFA-1) to intercellular
      adhesion molecule-1 (ICAM-1) mediates leukocyte adhesion under force. Using a
      biomembrane force probe capable of measuring single bond interactions, we showed
      ICAM-1 binding to LFA-1 at different conformations, including the bent
      conformation with the lowest affinity. We quantify how force and conformations of
      LFA-1 regulate its kinetics with ICAM-1. At zero-force, on-rates were
      substantially changed by conditions that differentially favor a bent or extended
      LFA-1 with a closed or open headpiece; but off-rates were identical. With
      increasing force, LFA-1/ICAM-1 bond lifetimes (reciprocal off-rates) first
      increased (catch bonds) and then decreased (slip bonds). Three states with
      distinct off-rates were identified from lifetime distributions. Force shifted the
      associated fractions from the short- to intermediate- and long-lived states,
      producing catch bonds at low forces, but increased their off-rates exponentially,
      converting catch to slip bonds at high forces. An internal ligand antagonist that
      blocks pulling of the alpha(7)-helix suppressed the intermediate-/long-lived
      states and eliminated catch bonds, revealing an internal catch bond between the
      alphaA and betaA domains. These results elucidate an allosteric mechanism for the
      mechanochemistry of LFA-1/ICAM-1 binding.

PMID- 20819953
TI  - Regulation of cAMP-dependent protein kinases: the human protein kinase X (PrKX)
      reveals the role of the catalytic subunit alphaH-alphaI loop.
AB  - cAMP-dependent protein kinases are reversibly complexed with any of the four
      isoforms of regulatory (R) subunits, which contain either a substrate or a
      pseudosubstrate autoinhibitory domain. The human protein kinase X (PrKX) is an
      exemption as it is inhibited only by pseudosubstrate inhibitors, i.e. RIalpha or
      RIbeta but not by substrate inhibitors RIIalpha or RIIbeta. Detailed examination
      of the capacity of five PrKX-like kinases ranging from human to protozoa
      (Trypanosoma brucei) to form holoenzymes with human R subunits in living cells
      shows that this preference for pseudosubstrate inhibitors is evolutionarily
      conserved. To elucidate the molecular basis of this inhibitory pattern, we
      applied bioluminescence resonance energy transfer and surface plasmon resonance
      in combination with site-directed mutagenesis. We observed that the conserved
      alphaH-alphaI loop residue Arg-283 in PrKX is crucial for its RI over RII
      preference, as a R283L mutant was able to form a holoenzyme complex with wild
      type RII subunits. Changing the corresponding alphaH-alphaI loop residue in PKA
      Calpha (L277R), significantly destabilized holoenzyme complexes in vitro, as cAMP
      mediated holoenzyme activation was facilitated by a factor of 2-4, and lead to a
      decreased affinity of the mutant C subunit for R subunits, significantly
      affecting RII containing holoenzymes.

PMID- 20819954
TI  - Crystal structure and mutational analysis of aminoacylhistidine dipeptidase from
      Vibrio alginolyticus reveal a new architecture of M20 metallopeptidases.
AB  - Aminoacylhistidine dipeptidases (PepD, EC 3.4.13.3) belong to the family of M20
      metallopeptidases from the metallopeptidase H clan that catalyze a broad range of
      dipeptide and tripeptide substrates, including L-carnosine and L-homocarnosine.
      Homocarnosine has been suggested as a precursor for the neurotransmitter gamma
      aminobutyric acid (GABA) and may mediate the antiseizure effects of GABAergic
      therapies. Here, we report the crystal structure of PepD from Vibrio
      alginolyticus and the results of mutational analysis of substrate-binding
      residues in the C-terminal as well as substrate specificity of the PepD catalytic
      domain-alone truncated protein PepD(CAT). The structure of PepD was found to
      exist as a homodimer, in which each monomer comprises a catalytic domain
      containing two zinc ions at the active site center for its hydrolytic function
      and a lid domain utilizing hydrogen bonds between helices to form the dimer
      interface. Although the PepD is structurally similar to PepV, which exists as a
      monomer, putative substrate-binding residues reside in different topological
      regions of the polypeptide chain. In addition, the lid domain of the PepD
      contains an "extra" domain not observed in related M20 family metallopeptidases
      with a dimeric structure. Mutational assays confirmed both the putative di-zinc
      allocations and the architecture of substrate recognition. In addition, the
      catalytic domain-alone truncated PepD(CAT) exhibited substrate specificity to l
      homocarnosine compared with that of the wild-type PepD, indicating a potential
      value in applications of PepD(CAT) for GABAergic therapies or neuroprotection.

PMID- 20819955
TI  - Patient INformation about Options for Treatment (PINOT): a prospective national
      study of information given to incident CKD Stage 5 patients.
AB  - BACKGROUND: Informed decision-making requires the presentation of all possible
      courses of action; however, it is unclear what proportion of Stage 5 chronic
      kidney disease (CKD) patients are routinely informed of all their treatment
      options. The aim of this study was to determine the effect of patient and unit
      characteristics on the type and timing of information provided. METHODS: A
      prospective national multi-centre study of information was given to incident pre
      emptive transplant, dialysis and conservatively managed patients in Australian
      renal units, over a 3-month period. RESULTS: Sixty-six of 73 renal units
      participated in the study. Seven hundred and twenty-one incident CKD Stage 5
      patients including 102 who chose not to dialyse were identified. Of these, 603
      (84%) were presented with information about their options prior to commencing
      treatment. Three quarters (n = 543) were presented with home dialysis, one-third
      (n = 230) pre-emptive transplantation and 65% (n = 470) were informed about
      conservative care as an option. Patients were more likely to receive information
      prior to commencing treatment if they were known to a nephrologist for more than
      3 months (OR 7.29, 95% CI 3.86-13.79) or were treated in small units with < 100
      dialysis patients (OR 2.40, 95% CI 1.26-4.60). The mean estimated glomerular
      filtration rate at the time information was first presented was 13.3 mL/min/1.73
      m(2) (95% CI 12.7-13.8) and mean serum creatinine was 449 MUmol/L (95% CI 431
      467). CONCLUSIONS: Most Australian patients were informed of their treatment
      options prior to starting treatment, albeit in late stage CKD. Earlier education
      and support for informed decision-making may help optimize the uptake of pre
      emptive transplantation and home dialysis therapies.

PMID- 20819956
TI  - Dent's disease: chloride-proton exchange controls proximal tubule endocytosis.

PMID- 20819957
TI  - Temporal waves of coherent gene expression during Drosophila embryogenesis.
AB  - MOTIVATION: Animal development depends on localized patterns of gene expression.
      Whole-genome methods permit the global identification of differential expression
      patterns. However, most gene-expression-clustering methods focus on the analysis
      of entire expression profiles, rather than temporal segments or time windows.
      RESULTS: In the current study, local clustering of temporal time windows was
      applied to developing embryos of the fruitfly, Drosophila melanogaster. Large
      scale developmental events, involving temporal activation of hundreds of genes,
      were identified as discrete gene clusters. The time-duration analysis revealed
      six temporal waves of coherent gene expression during Drosophila embryogenesis.
      The most powerful expression waves preceded major morphogenetic movements, such
      as germ band elongation and dorsal closure. These waves of gene expression
      coincide with the inhibition of maternal transcripts during early development,
      the specification of ectoderm, differentiation of the nervous system,
      differentiation of the digestive tract, deposition of the larval cuticle and the
      reorganization of the cytoskeleton during global morphogenetic events. We discuss
      the implications of these findings with respect to the gene regulatory networks
      governing Drosophila development. AVAILABILITY: Data and software are available
      from the UC Berkeley web resource http://flydev.berkeley.edu/cgi-bin/GTEM/dmap_dm
      ag/index_dmap.htm

PMID- 20819958
TI  - The mRNA landscape at yeast translation initiation sites.
AB  - SUMMARY: Although translation initiation has been well studied, many questions
      remain in elucidating its mechanisms. An ongoing challenge is to understand how
      ribosomes choose a translation initiation site (TIS). To gain new insights, we
      analyzed large sets of TISs with the aim of identifying common characteristics
      that are potentially of functional importance. Nucleotide sequence context has
      previously been demonstrated to play an important role in the ribosome's
      selection of a TIS, and mRNA secondary structure is also emerging as a
      contributing factor. Here, we analyze mRNA secondary structure using the folding
      predictions of the RNAfold algorithm. We present a method for analyzing these
      results using a rank-ordering approach to assess the overall degree of predicted
      secondary structure in a given region of mRNA. In addition, we used a modified
      version of the algorithm that makes use of only a subset of the standard
      version's output to incorporate base-pairing polarity constraints suggested by
      the ribosome scanning process. These methods were employed to study the TISs of
      1735 genes in Saccharomyces cerevisiae. Trends in base composition and base
      pairing probabilities suggest that efficient translation initiation and high
      protein expression are aided by reduced secondary structure upstream and
      downstream of the TIS. However, the downstream reduction is not observed for sets
      of TISs with nucleotide sequence contexts unfavorable for translation initiation,
      consistent with previous suggestions that secondary structure downstream of the
      ribosome can facilitate TIS recognition.

PMID- 20819959
TI  - Identification of protein binding surfaces using surface triplet propensities.
AB  - MOTIVATION: The ability to reliably predict protein-protein and protein-ligand
      interactions is important for identifying druggable binding sites and for
      understanding how proteins communicate. Most currently available algorithms
      identify cavities on the protein surface as potential ligand recognition sites.
      The method described here does not explicitly look for cavities but uses small
      surface patches consisting of triplets of adjacent surface atomic groups that can
      be touched simultaneously by a probe sphere representing a solvent molecule. A
      total of 455 different types of triplets can be identified. A training set of 309
      protein-ligand protein X-ray structures has been used to generate interface
      propensities for the triplets, which can be used to predict their involvement in
      ligand-binding interactions. RESULTS: The success rate for locating protein
      ligand binding sites on protein surfaces using this new surface triplet
      propensities (STP) algorithm is 88% which compares well with currently available
      grid-based and energy-based approaches. Q-SiteFinder's dataset (Laurie and
      Jackson, 2005. Bioinformatics, 21, 1908-1916) was used to show the favorable
      performance of STP. An analysis of the different triplet types showed that higher
      ligand binding propensity is related to more polarizable surfaces. The
      interaction statistics between triplet atoms on the protein surface and ligand
      atoms have been used to estimate statistical free energies of interaction. The
      DeltaG(stat) for halogen atoms interacting with hydrophobic triplets is -0.6
      kcal/mol and an estimate of the maximal DeltaG(stat) for a ligand atom
      interacting with a triplet in a binding pocket is -1.45 kcal/mol. AVAILABILITY:
      Freely available online at http://opus.bch.ed.ac.uk/stp. Website implemented in
      Php, with all major browsers supported. CONTACT: m.walkinshaw@ed.ac.uk
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 20819960
TI  - Incidence of maternal and paternal depression in primary care: a cohort study
      using a primary care database.
AB  - OBJECTIVE: To examine incidence, trends, and correlates of parental depression in
      primary care from 0 to 12 years of child age. DESIGN: Prospective cohort study.
      SETTING: Primary care records from more than 350 general practices in The Health
      Improvement Network database from 1993 to 2007. PARTICIPANTS: A total of 86 957
      mother, father, and child triads identified in The Health Improvement Network
      database by linking mothers and babies and then identifying an adult household
      man. Depressed parents were identified using Read code entries for depression and
      antidepressant prescriptions. MAIN EXPOSURES: Child age, parental age at the
      birth, and area deprivation quintile. MAIN OUTCOME MEASURES: Incidence rates for
      maternal and paternal episodes of depression. RESULTS: Overall incidences of
      depression from the birth of the child up to age 12 years were 7.53 per 100
      person-years for mothers and 2.69 per 100 person-years for fathers. Depression
      was highest in the first year post partum (13.93 and 3.56 per 100 person-years
      among mothers and fathers, respectively). By 12 years of child age, 39% of
      mothers and 21% of fathers had experienced an episode of depression. A history of
      depression, lower parental age at the birth of the child, and higher social
      deprivation were associated with a higher incidence of parental depression.
      CONCLUSIONS: Parents are at highest risk for depression in the first year after
      the birth of their child. Parents with a history of depression, younger parents,
      and those from deprived areas are particularly vulnerable to depression. There is
      a need for appropriate recognition and management of parental depression in
      primary care.

PMID- 20819961
TI  - Postinfectious fatigue in adolescents and physical activity.
AB  - OBJECTIVE: To compare adolescents who do and do not recover from acute infectious
      mononucleosis in terms of fatigue severity and activity levels before, during,
      and in the 2 years following infection. DESIGN: Prospective case-control study.
      SETTING: The baseline and 12- and 24-month evaluations occurred in the subjects'
      homes. The 6-month outpatient visit occurred at Children's Memorial Hospital in
      Chicago, Illinois. PARTICIPANTS: Three hundred one adolescents (aged 12-18 years)
      with acute infectious mononucleosis. MAIN EXPOSURES: All participants were
      evaluated at baseline (during active infection). Six months following infection,
      39 of them met criteria for chronic fatigue syndrome. These subjects were matched
      by sex and Tanner stage to 39 randomly selected screened-negative subjects. Both
      groups were reevaluated at 12- and 24-month follow-ups. OUTCOME MEASURES: Scores
      from the Fatigue Severity Scale and the Modifiable Activity Questionnaire.
      RESULTS: For both groups, physical activity levels declined and sleep increased
      as a result of having mononucleosis. Compared with their matched controls,
      adolescents with chronic fatigue syndrome reported significantly higher levels of
      fatigue at all points and spent significantly more time sleeping during the day 6
      and 12 months following infection. The 2 groups did not differ significantly in
      terms of physical activity levels before, during, or after infection. There was a
      consistent trend for decreased physical activity in the chronic fatigue syndrome
      group. CONCLUSIONS: Adolescents with chronic fatigue syndrome appear to be
      pushing themselves in an attempt to maintain similar activity levels as their
      peers, but paying for it in terms of fatigue severity and an increased need for
      sleep, particularly during the day.

PMID- 20819962
TI  - Adolescent chronic fatigue syndrome: a follow-up study.
AB  - OBJECTIVE: To describe the symptomatic and educational long-term outcomes, health
      care use, and risk factors of nonrecovery in adolescent chronic fatigue syndrome
      (CFS). DESIGN: Follow-up study. SETTING: Academic pediatric hospital.
      PARTICIPANTS: Sixty adolescents with CFS. INTERVENTIONS: Regular care. OUTCOME
      MEASURES: The Checklist Individual Strength, Child Health Questionnaire, and a
      general questionnaire regarding further symptoms, school attendance, work
      attendance, and treatment. RESULTS: Complete measurements were returned for 54
      adolescents (90%). At initial assessment, their mean (SD) age was 16.0 (1.5)
      years and 20.4% were male. The mean follow-up duration was 2.2 years. At follow
      up, the mean (SD) age was 18.2 (1.5) years; 28 adolescents (51.9%) had nearly
      complete improvement of symptoms but 26 (48.1%) did not experience improvement.
      Adolescents who attended school (n = 41) had missed an average of 33% of classes
      during the last month. The rest (n = 13) had worked an average of 38.7% of a full
      time job during the last month. A total of 66.7% of subjects were treated by a
      physiotherapist, 38.9% were clinically treated in rehabilitation, 48.1% had
      received psychological support, and 53.7% had used alternative treatment.
      CONCLUSIONS: About half of the adolescents had recovered from CFS at follow-up.
      The other half was still severely fatigued and physically impaired. Health care
      use had been high, and school and work attendance were low. Older age at
      inclusion was a risk factor, and pain, poor mental health, self-esteem, and
      general health perception at outcome were associated with an unfavorable outcome.
      Future research should focus on customizing existing treatment and studying
      additional treatment options.

PMID- 20819963
TI  - Biochemical and vascular aspects of pediatric chronic fatigue syndrome.
AB  - OBJECTIVE: To evaluate the biochemical and vascular aspects of pediatric chronic
      fatigue syndrome/myalgic encephalomyelitis (CFS/ME). DESIGN: Cross-sectional
      clinical study. SETTING: Tayside, Scotland, United Kingdom. PARTICIPANTS: Twenty
      five children with CFS/ME and 23 healthy children recruited from throughout the
      United Kingdom. INTERVENTIONS: Participants underwent a full clinical examination
      to establish a diagnosis of CFS/ME and were asked to describe and score their
      CFS/ME symptoms. Biochemical markers were measured. Arterial wave reflection was
      estimated to assess systemic arterial stiffness. MAIN OUTCOME MEASURES: Markers
      of oxidative stress and free radicals, C-reactive protein level, white blood cell
      apoptosis, and arterial wave reflection. RESULTS: Children with CFS/ME had
      increased oxidative stress compared with control individuals (isoprostanes:
      252.30 vs 215.60 pg/mL, P = .007; vitamin C, mean [SD]: 0.84 [0.26] vs 1.15
      [0.28] mg/dL, P < .001; vitamin E, 8.72 [2.39] vs 10.94 [3.46] microg/mL, P =
      .01) and increased white blood cell apoptosis (neutrophils: 53.7% vs 35.7%, P =
      .005; lymphocytes: 40.1% vs 24.6%, P = .009). Arterial stiffness variables did
      not differ significantly between groups (mean augmentation index, -0.57% vs 
      0.47%, P = .09); however, the derived variables significantly correlated with
      total (r = 0.543, P = .02) and low-density lipoprotein (r = 0.631, P = .004)
      cholesterol in patients with CFS/ME but not in controls. CONCLUSIONS: Biomedical
      anomalies seen in adults with CFS/ME-increased oxidative stress and increased
      white blood cell apoptosis-can also be observed in children with clinically
      diagnosed CFS/ME compared with matched controls. Unlike in their adult
      counterparts, however, arterial stiffness remained within the reference range in
      these pediatric patients.

PMID- 20819964
TI  - Cerebrospinal fluid enterovirus testing in infants 56 days or younger.
AB  - OBJECTIVE: To determine whether cerebrospinal fluid (CSF) enterovirus polymerase
      chain reaction (PCR) testing of febrile neonates is associated with a shorter
      hospital length of stay (LOS). DESIGN: Retrospective cohort study. SETTING: Urban
      tertiary care children's hospital emergency department. PARTICIPANTS: Febrile
      infants 56 days or younger evaluated by means of lumbar puncture. MAIN EXPOSURE:
      Performance of CSF enterovirus PCR testing. MAIN OUTCOME MEASURE: Hospital LOS.
      RESULTS: A CSF enterovirus PCR test was performed in 361 of 1231 eligible infants
      (29.3%); 89 of those tested (24.7%) were positive. The median LOS was 2 days. In
      multivariable analysis, CSF enterovirus PCR testing was associated with a 26.0%
      shorter LOS for infants with a positive test result (adjusted beta coefficient, 
      0.305; 95% confidence interval, -0.457 to -0.153; P < .001) and an 8.0% longer
      LOS for those with a negative test result (0.075; -0.021 to 0.171; P = .12)
      compared with untested infants. In stratified analysis, LOS was shorter for all
      infants 28 days or younger who tested positive regardless of receipt of
      antibiotics before lumbar puncture. For infants 29 to 56 days old, a positive
      test result was associated with a shorter LOS only in those not previously
      receiving antibiotics. The median (interquartile range) turnaround time for CSF
      enterovirus PCR testing was 22.2 (15.1-27.4) hours, with no effect of turnaround
      time on LOS. CONCLUSIONS: Among infants 56 days or younger, a positive CSF
      enterovirus PCR test result was associated with a shorter LOS compared with
      untested infants. The CSF enterovirus PCR test may improve the care of infants
      with fever.

PMID- 20819965
TI  - Parental hopeful patterns of thinking, emotions, and pediatric palliative care
      decision making: a prospective cohort study.
AB  - OBJECTIVE: To test the hypothesis that hopeful patterns of thoughts and emotions
      of parents of pediatric patients receiving palliative care consultative services
      are related to subsequent decisions, specifically regarding limit of intervention
      (LOI) orders. DESIGN: Prospective cohort study. SETTING: Children's hospital and
      surrounding region. PARTICIPANTS: Thirty-three pediatric patients receiving
      palliative care consultative services who did not have LOI orders at time of
      cohort entry and their 43 parental adults. MAIN EXPOSURES: Parental levels at
      time of cohort entry of hopeful patterns of thinking and emotions, in conjunction
      with perceptions about patients' health trajectories. MAIN OUTCOME MEASURE:
      Enactment of an LOI order after entry into the cohort. RESULTS: During the 6
      months of observation, 14 patients (42.4%) had an LOI order enacted. In adjusted
      analyses, higher levels of parental hopeful patterns of thinking were
      significantly associated with increased odds of enactment of an LOI order
      (adjusted odds ratio [AOR], 2.73; 95% confidence interval [CI], 1.04-7.22).
      Increased odds of LOI enactment were associated to nonsignificant degrees with
      lower levels of parental positive affect (AOR, 0.44; 95% CI, 0.17-1.12), higher
      levels of parental negative affect (AOR, 2.02; 95% CI, 0.98-4.16), and parental
      perceptions of worsening health over time (AOR, 1.72; 95% CI, 0.73-4.07).
      CONCLUSION: For pediatric patients receiving palliative care consultative
      services, higher levels of parents' hopeful patterns of thinking are associated
      with subsequent enactment of LOI orders, suggesting that emotional and cognitive
      processes have a combined effect on medical decision making.

PMID- 20819966
TI  - Shortened nighttime sleep duration in early life and subsequent childhood
      obesity.
AB  - OBJECTIVE: To test associations between daytime and nighttime sleep duration and
      subsequent obesity in children and adolescents. DESIGN: Prospective cohort.
      SETTING: Panel Survey of Income Dynamics Child Development Supplements (1997 and
      2002) from US children. PARTICIPANTS: Subjects aged 0 to 13 years (n = 1930) at
      baseline (1997). MAIN EXPOSURES: Binary indicators of short daytime and nighttime
      sleep duration (<25th percentile of age-normalized sleep scores) at baseline.
      MAIN OUTCOME MEASURES: Body mass index at follow-up (2002) was converted to age-
      and sex-specific z scores and trichotomized (normal weight, overweight, obese)
      using established cut points. Ordered logistic regression was used to model body
      mass index classification as a function of short daytime and nighttime sleep at
      baseline and follow-up, and important covariates included socioeconomic status,
      parents' body mass index, and, for children older than 4 years, body mass index
      at baseline. RESULTS: For younger children (aged 0-4 years at baseline), short
      duration of nighttime sleep at baseline was strongly associated with increased
      risk of subsequent overweight or obesity (odds ratio = 1.80; 95% confidence
      interval, 1.16-2.80). For older children (aged 5-13 years), baseline sleep was
      not associated with subsequent weight status; however, contemporaneous sleep was
      inversely associated. Daytime sleep had little effect on subsequent obesity in
      either group. CONCLUSIONS: Shortened sleep duration in early life is a modifiable
      risk factor with important implications for obesity prevention and treatment.
      Insufficient nighttime sleep among infants and preschool-aged children may be a
      lasting risk factor for subsequent obesity. Napping does not appear to be a
      substitute for nighttime sleep in terms of obesity prevention.

PMID- 20819967
TI  - Carotid intima-media thickness and serum endothelial marker levels in obese
      children with metabolic syndrome.
AB  - OBJECTIVE: To investigate carotid intima-media thickness (IMT) and serum
      endothelial marker levels in obese Chinese children. DESIGN: Observational and
      descriptive study. SETTING: Hangzhou, China. PARTICIPANTS: A total 131 obese
      children, including 29 with at least 2 components of metabolic syndrome (MS) (MS
      group), 102 with less than 2 components of MS (obese group), and 31 nonobese
      children (control group) were enrolled. MAIN OUTCOME MEASURES: Intima-media
      thickness, von Willebrand factor (vWF) level, and thrombomodulin level. RESULTS:
      Compared with the control group, the obese group had greater IMT and higher vWF
      level (P < .05 for all). The mean (SD) vWF levels in the obese, MS, and control
      groups were 2.08 (0.78), 2.42 (0.98), and 1.54 (0.48) IU/mL, respectively, which
      were significantly different (P < .001). Intima-media thickness in the obese and
      MS groups was significantly greater than that in the control group. Intima-media
      thickness in the MS group was greater than that in the obese group. Multiple
      regression analysis showed that ratio of waist to height, vWF level, and
      triglycerides level were independent determinants of IMT. CONCLUSIONS: Our
      findings suggest endothelial injury in obese children. Intima-media thickness and
      vWF level might be useful to identify the degree of endothelial damage.

PMID- 20819968
TI  - Impaired cardiac function among obese adolescents: effect of aerobic interval
      training.
AB  - OBJECTIVES: To measure cardiac function before and after 3 months of aerobic
      interval training in obese adolescents and to compare the findings with those in
      lean counterparts. DESIGN: Exercise intervention study. Cardiac function was
      assessed by echocardiography and maximal oxygen uptake by ergospirometry.
      SETTING: The obese adolescents were referred from general practice to the St Olav
      University Hospital, Trondheim, Norway, and the control group was recruited from
      2 schools. PARTICIPANTS: Ten obese adolescents (mean [SD] age, 14.8 [1.2] years;
      mean [SD] body mass index {BMI; calculated as weight in kilograms divided by
      height in meters squared}, 33.5 [4.3]) and 10 lean counterparts (mean [SD] age,
      14.9 [1.3] years; mean [SD] BMI, 20.4 [3.0]) participated. Intervention Aerobic
      interval training (4 x 4 minutes at 90% of maximal heart rate, 40 minutes of
      training in total) was performed twice per week for 13 weeks among the obese
      adolescents, whereas the lean counterparts only performed the tests. MAIN OUTCOME
      MEASURES: Left ventricular end-diastolic volume, stroke volume, and maximal
      oxygen uptake. RESULTS: Maximal oxygen uptake was 41.4% lower among the obese
      adolescents compared with the lean counterparts, but the maximal oxygen uptake
      increased by 8.6% (P = .008) after intervention. Obese adolescents initially had
      7.8% and 14.5% lower left ventricular end-diastolic and stroke volumes, 21.3%
      reduced global strain rate and 16.3% global strain, reduced mitral annulus
      excursion and systolic/diastolic tissue velocity, longer isovolumic relaxation
      time, and longer deceleration time compared with the lean counterparts. No group
      difference was observed after the intervention. Aerobic interval training
      increased the ejection fraction but was lower compared with the lean
      counterparts. Aerobic interval training reduced fat content by 2.0% (P = .005)
      among the obese adolescents. CONCLUSIONS: Aerobic interval training almost
      restored an impaired systolic and diastolic cardiac function among obese
      adolescents when compared with lean counterparts. These results may have
      implications for future treatment programs for obese adolescents.

PMID- 20819970
TI  - Changes in human immunodeficiency virus testing rates among urban adolescents
      after introduction of routine and rapid testing.
AB  - OBJECTIVES: To examine human immunodeficiency virus (HIV) testing rates among
      adolescents during a 3-year period to determine (1) if the rate of testing
      increased after publication of national recommendations for routine HIV testing
      in 2006, and again after the introduction of rapid testing in the clinic in 2007,
      and (2) factors associated with HIV testing. DESIGN: Retrospective medical record
      review. SETTING: Urban hospital-based adolescent primary care clinic.
      PARTICIPANTS: Thirteen- to 22-year-old sexually experienced patients who had
      computerized billing data reflecting testing for sexually transmitted infections,
      including HIV. OUTCOME MEASURES: Rates of HIV testing for each of 3 one-year
      phases-phase 1 (pre-routine testing recommendations), phase 2 (post-routine
      testing recommendations but pre-rapid testing), and phase 3 (post-rapid testing)
      and factors associated with HIV testing. RESULTS: In total, 9491 patients were
      included. The rate of HIV testing in phase 2 was significantly higher than the
      rate of testing in phase 1 (27.7% vs 12.6%, P < .001). The rate of testing in
      phase 3 was significantly higher than the rate of testing in phase 2 (44.6% vs
      27.7%, P < .001) and phase 1 (P < .001). Factors independently associated with
      HIV testing included phase, older age, male sex, race, public insurance status,
      and having a genitourinary-related diagnosis during the same phase. CONCLUSIONS:
      The HIV testing rates increased significantly following publication of
      recommendations for routine testing and further increased following introduction
      of rapid testing. Combining routine and rapid testing strategies may increase
      uptake of HIV testing among adolescents in primary care settings.

PMID- 20819969
TI  - Perfluorooctanoic acid, perfluorooctanesulfonate, and serum lipids in children
      and adolescents: results from the C8 Health Project.
AB  - BACKGROUND: Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) are
      man-made compounds with widespread presence in human sera. In previous
      occupational and adult studies, PFOA and PFOS were positively associated with
      serum lipid levels. OBJECTIVE: To interrogate associations between PFOA and PFOS
      and serum lipids in children and adolescents. DESIGN: Cross-sectional community
      based study. SETTING: Mid-Ohio River Valley. PARTICIPANTS: A total of 12 476
      children and adolescents included in the C8 Health Project, which resulted from
      the pretrial settlement of a class action lawsuit pursuant to PFOA contamination
      of the drinking water supply. MAIN OUTCOME MEASURES: Serum lipids (total, high
      density lipoprotein [HDL-C], and low-density lipoprotein [LDL-C] cholesterol and
      fasting triglycerides). RESULTS: Mean (SD) serum PFOA and PFOS concentrations
      were 69.2 (111.9) ng/mL and 22.7 (12.6) ng/mL, respectively. In linear regression
      after adjustment for covariables, PFOA was significantly associated with
      increased total cholesterol and LDL-C, and PFOS was significantly associated with
      increased total cholesterol, HDL-C, and LDL-C. Using general linear model
      analysis of covariance, between the first and fifth quintiles of PFOA there was a
      4.6-mg/dL and a 3.8-mg/dL increase in the adjusted mean levels of total
      cholesterol and LDL-C levels, respectively, and an 8.5-mg/dL and a 5.8-mg/dL
      increase in the adjusted mean levels of total cholesterol and LDL-C,
      respectively, between the first and fifth quintiles of PFOS. Increases were 10
      mg/dL for some age- and sex-group strata. Observed effects were nonlinear, with
      larger increases in total cholesterol and LDL-C levels occurring at the lowest
      range, particularly of PFOA. CONCLUSION: Although the epidemiologic and cross
      sectional natures of this study limit causal inferences, the consistently
      observed associations between increasing PFOA and PFOS and elevated total
      cholesterol and LDL-C levels warrant further study.

PMID- 20819971
TI  - Picture of the month--quiz case. Kindler syndrome.

PMID- 20819972
TI  - Marketing, leadership, and the health of children.

PMID- 20819973
TI  - Chronic fatigue syndrome in adolescence: where to from here?

PMID- 20819974
TI  - Trial effect in newly diagnosed pediatric acute lymphoblastic leukemia.

PMID- 20819975
TI  - When is a review article not a review article?

PMID- 20819976
TI  - Advice for patients. Exercise.

PMID- 20819977
TI  - Preference for geometric patterns early in life as a risk factor for autism.
AB  - CONTEXT: Early identification efforts are essential for the early treatment of
      the symptoms of autism but can only occur if robust risk factors are found.
      Children with autism often engage in repetitive behaviors and anecdotally prefer
      to visually examine geometric repetition, such as the moving blade of a fan or
      the spinning of a car wheel. The extent to which a preference for looking at
      geometric repetition is an early risk factor for autism has yet to be examined.
      OBJECTIVES: To determine if toddlers with an autism spectrum disorder (ASD) aged
      14 to 42 months prefer to visually examine dynamic geometric images more than
      social images and to determine if visual fixation patterns can correctly classify
      a toddler as having an ASD. DESIGN: Toddlers were presented with a 1-minute movie
      depicting moving geometric patterns on 1 side of a video monitor and children in
      high action, such as dancing or doing yoga, on the other. Using this preferential
      looking paradigm, total fixation duration and the number of saccades within each
      movie type were examined using eye tracking technology. SETTING: University of
      California, San Diego Autism Center of Excellence. PARTICIPANTS: One hundred ten
      toddlers participated in final analyses (37 with an ASD, 22 with developmental
      delay, and 51 typical developing toddlers). MAIN OUTCOME MEASURE: Total fixation
      time within the geometric patterns or social images and the number of saccades
      were compared between diagnostic groups. RESULTS: Overall, toddlers with an ASD
      as young as 14 months spent significantly more time fixating on dynamic geometric
      images than other diagnostic groups. If a toddler spent more than 69% of his or
      her time fixating on geometric patterns, then the positive predictive value for
      accurately classifying that toddler as having an ASD was 100%. CONCLUSION: A
      preference for geometric patterns early in life may be a novel and easily
      detectable early signature of infants and toddlers at risk for autism.

PMID- 20819978
TI  - Pilot study of psilocybin treatment for anxiety in patients with advanced-stage
      cancer.
AB  - CONTEXT: Researchers conducted extensive investigations of hallucinogens in the
      1950s and 1960s. By the early 1970s, however, political and cultural pressures
      forced the cessation of all projects. This investigation reexamines a potentially
      promising clinical application of hallucinogens in the treatment of anxiety
      reactive to advanced-stage cancer. OBJECTIVE: To explore the safety and efficacy
      of psilocybin in patients with advanced-stage cancer and reactive anxiety.
      DESIGN: A double-blind, placebo-controlled study of patients with advanced-stage
      cancer and anxiety, with subjects acting as their own control, using a moderate
      dose (0.2 mg/kg) of psilocybin. SETTING: A clinical research unit within a large
      public sector academic medical center. PARTICIPANTS: Twelve adults with advanced
      stage cancer and anxiety. MAIN OUTCOME MEASURES: In addition to monitoring safety
      and subjective experience before and during experimental treatment sessions,
      follow-up data including results from the Beck Depression Inventory, Profile of
      Mood States, and State-Trait Anxiety Inventory were collected unblinded for 6
      months after treatment. RESULTS: Safe physiological and psychological responses
      were documented during treatment sessions. There were no clinically significant
      adverse events with psilocybin. The State-Trait Anxiety Inventory trait anxiety
      subscale demonstrated a significant reduction in anxiety at 1 and 3 months after
      treatment. The Beck Depression Inventory revealed an improvement of mood that
      reached significance at 6 months; the Profile of Mood States identified mood
      improvement after treatment with psilocybin that approached but did not reach
      significance. CONCLUSIONS: This study established the feasibility and safety of
      administering moderate doses of psilocybin to patients with advanced-stage cancer
      and anxiety. Some of the data revealed a positive trend toward improved mood and
      anxiety. These results support the need for more research in this long-neglected
      field. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00302744.

PMID- 20819980
TI  - Picasso's Guernica.

PMID- 20819979
TI  - Altered expression of regulators of the cortical chloride transporters NKCC1 and
      KCC2 in schizophrenia.
AB  - CONTEXT: Disturbances in markers of cortical gamma-aminobutyric acid
      neurotransmission are a common finding in schizophrenia. The nature of gamma
      aminobutyric acid neurotransmission (hyperpolarizing or depolarizing) depends on
      the local intracellular chloride concentration. In the central nervous system,
      the intracellular chloride level is determined by the activity of 2 cation
      chloride transporters, NKCC1 and KCC2. The activities of these transporters are
      in turn regulated by a network of serine-threonine kinases that includes OXSR1,
      STK39, and the WNK kinases WNK1, WNK3, and WNK4. OBJECTIVE: To compare the levels
      of NKCC1, KCC2, OXSR1, STK39, WNK1, WNK3, and WNK4 transcripts in prefrontal
      cortex area 9 between subjects with schizophrenia and healthy comparison
      subjects. DESIGN: Real-time quantitative polymerase chain reaction technique was
      used to measure transcript levels in the prefrontal cortex. SETTING: Human brain
      specimens were obtained from autopsies conducted at the Allegheny County Medical
      Examiner's Office, Pittsburgh, Pennsylvania. PARTICIPANTS: Postmortem brain
      specimens from 42 subjects with schizophrenia and 42 matched healthy comparison
      subjects. Brain specimens from 18 macaque monkeys exposed to haloperidol,
      olanzapine, or sham long-term. MAIN OUTCOME MEASURES: Relative expression levels
      for NKCC1, KCC2, OXSR1, STK39, WNK1, WNK3, and WNK4 transcripts compared with the
      mean expression level of 3 housekeeping transcripts. RESULTS: OXSR1 and WNK3
      transcripts were substantially overexpressed in subjects with schizophrenia
      relative to comparison subjects. In contrast, NKCC1, KCC2, STK39, WNK1, and WNK4
      transcript levels did not differ between subject groups. OXSR1 and WNK3
      transcript expression levels were not changed in antipsychotic-exposed monkeys
      and were not affected by potential confounding factors in the subjects with
      schizophrenia. CONCLUSION: In schizophrenia, increased expression levels, and
      possibly increased kinase activities, of OXSR1 and WNK3 may shift the balance of
      chloride transport by NKCC1 and KCC2 and alter the nature of gamma-aminobutyric
      acid neurotransmission in the prefrontal cortex.

PMID- 20819981
TI  - Modification of cognitive performance in schizophrenia by complexin 2 gene
      polymorphisms.
AB  - CONTEXT: Schizophrenia is the collective term for a heterogeneous group of mental
      disorders with a still obscure biological basis. In particular, the specific
      contribution of risk or candidate gene variants to the complex schizophrenic
      phenotype is largely unknown. OBJECTIVE: To prepare the ground for a novel
      "phenomics" approach, a unique schizophrenia patient database was established by
      GRAS (Gottingen Research Association for Schizophrenia), designed to allow
      association of genetic information with quantifiable phenotypes.Because synaptic
      dysfunction plays a key role in schizophrenia, the complexin 2 gene (CPLX2) was
      examined in the first phenotype-based genetic association study (PGAS) of GRAS
      [corrected] DESIGN: Subsequent to a classic case-control approach, we analyzed
      the contribution of CPLX2 polymorphisms to discrete cognitive domains within the
      schizophrenic population. To gain mechanistic insight into how certain CPLX2
      variants influence gene expression and function, peripheral blood mononuclear
      cells of patients, Cplx -null mutant mice, and transfected cells were
      investigated. SETTING: Coordinating research center (Max Planck Institute of
      Experimental Medicine) and 23 collaborating psychiatric centers all over Germany.
      PARTICIPANTS: One thousand seventy-one patients with schizophrenia (DSM-IV)
      examined by an invariant investigator team, resulting in the GRAS database with
      more than 3000 phenotypic data points per patient, and 1079 healthy control
      subjects of comparable ethnicity. Main Outcome Measure Cognitive performance
      including executive functioning, reasoning, and verbal learning/memory. RESULTS:
      Six single-nucleotide polymorphisms, distributed over the whole CPLX2 gene, were
      found to be highly associated with current cognition of schizophrenic subjects
      but only marginally with premorbid intelligence. Correspondingly, in Cplx2 -null
      mutant mice, prominent cognitive loss of function was obtained only in
      combination with a minor brain lesion applied during puberty, modeling a
      clinically relevant environmental risk ("second hit") for schizophrenia. In the
      human CPLX2 gene, 1 of the identified 6 cognition-relevant single-nucleotide
      polymorphisms, rs3822674 in the 3' untranslated region, was detected to influence
      microRNA-498 binding and gene expression. The same marker was associated with
      differential expression of CPLX2 in peripheral blood mononuclear cells.
      CONCLUSIONS: The PGAS allows identification of marker-associated
      clinical/biological traits. Current cognitive performance in schizophrenic
      patients is modified by CPLX2 variants modulating posttranscriptional gene
      expression.

PMID- 20819982
TI  - Neonatal vitamin D status and risk of schizophrenia: a population-based case
      control study.
AB  - CONTEXT: Clues from the epidemiology of schizophrenia suggest that low levels of
      developmental vitamin D may be associated with increased risk of schizophrenia.
      OBJECTIVE: To directly examine the association between neonatal vitamin D status
      and risk of schizophrenia. DESIGN: Individually matched case-control study drawn
      from a population-based cohort. SETTING: Danish national health registers and
      neonatal biobank. PARTICIPANTS: A total of 424 individuals with schizophrenia and
      424 controls matched for sex and date of birth. MAIN OUTCOME MEASURES: The
      concentration of 25 hydroxyvitamin D(3) (25[OH]D3) was assessed from neonatal
      dried blood samples using a highly sensitive liquid chromatography tandem mass
      spectroscopy method. Relative risks were calculated for the matched pairs when
      examined for quintiles of 25(OH)D3. RESULTS: Compared with neonates in the fourth
      quintile (with 25[OH]D3 concentrations between 40.5 and 50.9 nmol/L), those in
      each of the lower 3 quintiles had a significantly increased risk of schizophrenia
      (2-fold elevated risk). Unexpectedly, those in the highest quintile also had a
      significantly increased risk of schizophrenia. Based on this analysis, the
      population-attributable fraction associated with neonatal vitamin D status was
      44%. The relationship was not explained by a wide range of potential confounding
      or interacting variables. CONCLUSIONS: Both low and high concentrations of
      neonatal vitamin D are associated with increased risk of schizophrenia, and it is
      feasible that this exposure could contribute to a sizeable proportion of cases in
      Denmark. In light of the substantial public health implications of this finding,
      there is an urgent need to further explore the effect of vitamin D status on
      brain development and later mental health.

PMID- 20819984
TI  - Impaired intellect and memory: a missing link between genetic risk and
      schizophrenia?
AB  - CONTENT: The DSM-IV concept of schizophrenia offers diagnostic reliability but
      etiologic and pathologic heterogeneity, which probably contributes to the
      inconsistencies in genetic studies. One solution is to identify intermediate
      phenotypes, "narrower" constructs of liability, that hypothetically share genetic
      risk with the disorder. Although a variety of candidate intermediate phenotypes
      have emerged, few have explicitly quantified the extent of their genetic overlap
      with schizophrenia. OBJECTIVE: To quantify the net-shared genetic effects between
      schizophrenia and specific cognitive candidate intermediate phenotypes. DESIGN:
      Twin and family design. SETTING: Adult psychiatric research centers in the United
      States and the United Kingdom. PARTICIPANTS: A total of 2056 participants: 657
      patients with schizophrenia, 674 first-degree relatives (including co-twins), and
      725 controls. MAIN OUTCOME MEASURES: (1) Latent factors capturing the common
      variance between cognitive tasks, (2) separation of the latent factors into their
      genetic and environmental components, and (3) estimation of the net-shared
      genetic variance between the latent cognitive factors or intelligence and
      schizophrenia. RESULTS: Genetic factors contributed substantially to the total
      variance in cognition (immediate recall latent factor: 0.66; 95% confidence
      interval [CI], 0.62 to 0.85; delayed recall latent factor: 0.48; 0.42 to 0.55;
      and intelligence: 0.66; 0.62 to 0.71). The latent common factors for modality
      specific immediate and delayed recall and intelligence showed similar levels of
      phenotypic covariance with schizophrenia (immediate recall: -0.35; delayed
      recall: -0.37; and intelligence: -0.38), with 72%, 86%, and 89%, respectively,
      due to shared genetic effects with schizophrenia. Environmental effects accounted
      for little phenotypic correlation between cognition and schizophrenia.
      CONCLUSIONS: Using the largest international familial schizophrenia cohort to
      date, we showed that a substantial portion of the phenotypic correlation between
      schizophrenia and cognition is caused by shared genetic effects. However, because
      the phenotypic and genetic correlations are far from unity, the genetics of
      schizophrenia are clearly not merely the genetics of cognition.

PMID- 20819983
TI  - Effect of antipsychotic medication alone vs combined with psychosocial
      intervention on outcomes of early-stage schizophrenia: A randomized, 1-year
      study.
AB  - CONTEXT: Antipsychotic drugs are limited in their ability to improve the overall
      outcome of schizophrenia. Adding psychosocial treatment may produce greater
      improvement in functional outcome than does medication treatment alone.
      OBJECTIVE: To evaluate the effectiveness of antipsychotic medication alone vs
      combined with psychosocial intervention on outcomes of early-stage schizophrenia.
      DESIGN: Randomized controlled trial. SETTING: Ten clinical sites in China.
      PARTICIPANTS: Clinical sample of 1268 patients with early-stage schizophrenia
      treated from January 1, 2005, through October 31, 2007. Intervention Patients
      were randomly assigned to receive antipsychotic medication treatment only or
      antipsychotic medication plus 12 months of psychosocial intervention consisting
      of psychoeducation, family intervention, skills training, and cognitive behavior
      therapy administered during 48 group sessions. MAIN OUTCOME MEASURES: The rate of
      treatment discontinuation or change due to any cause, relapse or remission, and
      assessments of insight, treatment adherence, quality of life, and social
      functioning. RESULTS: The rates of treatment discontinuation or change due to any
      cause were 32.8% in the combined treatment group and 46.8% in the medication
      alone group. Comparisons with medication treatment alone showed lower risk of any
      cause discontinuation with combined treatment (hazard ratio, 0.62; 95% confidence
      interval, 0.52-0.74; P < .001) and lower risk of relapse with combined treatment
      (0.57; 0.44-0.74; P < .001). The combined treatment group exhibited greater
      improvement in insight (P < .001), social functioning (P = .002), activities of
      daily living (P < .001), and 4 domains of quality of life as measured by the
      Medical Outcomes Study 36-Item Short Form Health Survey (all P < or = .02).
      Furthermore, a significantly higher proportion of patients receiving combined
      treatment obtained employment or accessed education (P = .001). CONCLUSION:
      Compared with those receiving medication only, patients with early-stage
      schizophrenia receiving medication and psychosocial intervention have a lower
      rate of treatment discontinuation or change, a lower risk of relapse, and
      improved insight, quality of life, and social functioning. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00654576.

PMID- 20819985
TI  - Individuals, schools, and neighborhood: a multilevel longitudinal study of
      variation in incidence of psychotic disorders.
AB  - CONTEXT: Incidence of schizophrenia and other nonaffective psychoses is greater
      in urban than rural areas, but the reason is unclear. Few studies have examined
      whether both individual and neighborhood characteristics can explain this
      association. Furthermore, as has been shown for ethnicity, the effect of
      individual characteristics may depend on neighborhood context. OBJECTIVES: To
      examine (1) whether individual, school, or area characteristics are associated
      with psychosis and can explain the association with urbanicity and (2) whether
      effects of individual characteristics on risk of psychosis vary according to
      school context (reflecting both peer group and neighborhood effects). DESIGN:
      Multilevel longitudinal study of all individuals born in Sweden in 1972 and 1977.
      Diagnoses were identified through linkage with the Swedish National Patient
      Register until December 31, 2003. SETTING: Population-based. PARTICIPANTS: A
      total of 203 829 individuals with data at individual, school, municipality, and
      county levels. MAIN OUTCOME MEASURES: Any nonaffective psychosis, including
      schizophrenia (881 subjects; 0.43% cumulative incidence). For the study of
      interactions, the outcome was any psychosis (1944 subjects; 0.95% cumulative
      incidence). RESULTS: Almost all the variance in risk of nonaffective psychosis
      was explained by individual-level rather than higher-level variation. An
      association between urbanicity and nonaffective psychosis was explained by higher
      level characteristics, primarily school-level social fragmentation. We observed
      cross-level interactions between individual- and school-level markers of
      ethnicity, social fragmentation, and deprivation on risk of developing any
      psychotic disorder, all with qualitative patterns of interaction. CONCLUSIONS:
      The association between urbanicity and psychosis appears to be a reflection of
      increased social fragmentation present within cities. The qualitative
      interactions observed are consistent with a hypothesis that certain
      characteristics that define individuals as being different from most other people
      in their local environment may increase risk of psychosis. These findings have
      potentially important implications for understanding the etiology of psychotic
      disorders and for informing social policy.

PMID- 20819986
TI  - Birth weight, schizophrenia, and adult mental disorder: is risk confined to the
      smallest babies?
AB  - CONTEXT: Studies linking birth weight and mental illness onset are inconclusive.
      They have primarily focused on the World Health Organization low birth weight
      threshold (2500 g) and schizophrenia. To our knowledge, low birth weight per se
      has not been conclusively linked with schizophrenia risk and specificity of the
      effect to birth weight below the standard threshold or to particular psychiatric
      diagnoses has not been demonstrated. OBJECTIVES: To examine whether (1) low birth
      weight (<2500 g) is associated with increased risk for adult schizophrenia; (2)
      risk extends into the normal weight range; and (3) risk is confined to
      schizophrenia or linked to other adult mental illnesses. DESIGN: Population-based
      cohort study. SETTING: Sweden and Denmark. PARTICIPANTS: Singleton live births in
      Sweden (1973-1984) and Denmark (1979-1986) (N = 1.49 million). Births were linked
      to comprehensive national registers of psychiatric treatment, with follow-up to
      December 31, 2002 (Sweden), or to June 30, 2005 (Denmark). There were 5445 cases
      of schizophrenia and 57 455 cases of any adult psychiatric disorder. MAIN OUTCOME
      MEASURE: Crude and adjusted odds ratios for birth weight less than or more than
      3500 to 3999 g in consecutive 500-g strata (from 500-1499 g to > or =4500 g) for
      schizophrenia, any psychiatric diagnoses, and specified psychiatric diagnoses.
      RESULTS: Schizophrenia was associated with birth weight less than 2500 g. The
      association was not restricted to birth weight less than 2500 g and there was a
      significant linear trend of increasing odds ratios with decreasing birth weight
      across the birth weight range. This was mirrored for any psychiatric diagnosis
      and for each of the categories of psychiatric disorder. CONCLUSIONS: Findings
      suggest there is an association between birth weight and adult mental disorder,
      but there is no indication this effect is specific to birth weight less than 2500
      g or to schizophrenia. Future research should explore common disorder-specific
      mechanisms that may link birth weight to development of psychiatric disorder in
      adulthood.

PMID- 20819987
TI  - Bipolar disorder and violent crime: new evidence from population-based
      longitudinal studies and systematic review.
AB  - CONTEXT: Although bipolar disorder is associated with various adverse health
      outcomes, the relationship with violent crime is uncertain. OBJECTIVES: To
      determine the risk of violent crime in bipolar disorder and to contextualize the
      findings with a systematic review. DESIGN: Longitudinal investigations using
      general population and unaffected sibling control individuals. SETTING:
      Population-based registers of hospital discharge diagnoses, sociodemographic
      information, and violent crime in Sweden from January 1, 1973, through December
      31, 2004. PARTICIPANTS: Individuals with 2 or more discharge diagnoses of bipolar
      disorder (n = 3743), general population controls (n = 37 429), and unaffected
      full siblings of individuals with bipolar disorder (n = 4059). MAIN OUTCOME
      MEASURE: Violent crime (actions resulting in convictions for homicide, assault,
      robbery, arson, any sexual offense, illegal threats, or intimidation). RESULTS:
      During follow-up, 314 individuals with bipolar disorder (8.4%) committed violent
      crime compared with 1312 general population controls (3.5%) (adjusted odds ratio,
      2.3; 95% confidence interval, 2.0-2.6). The risk was mostly confined to patients
      with substance abuse comorbidity (adjusted odds ratio, 6.4; 95% confidence
      interval, 5.1-8.1). The risk increase was minimal in patients without substance
      abuse comorbidity (adjusted odds ratio, 1.3; 95% confidence interval, 1.0-1.5),
      which was further attenuated when unaffected full siblings of individuals with
      bipolar disorder were used as controls (1.1; 0.7-1.6). We found no differences in
      rates of violent crime by clinical subgroups (manic vs depressive or psychotic vs
      nonpsychotic). The systematic review identified 8 previous studies (n = 6383),
      with high heterogeneity between studies. Odds ratio for violence risk ranged from
      2 to 9. CONCLUSION: Although current guidelines for the management of individuals
      with bipolar disorder do not recommend routine risk assessment for violence, this
      assertion may need review in patients with comorbid substance abuse.

PMID- 20819988
TI  - Genetic variation in CACNA1C affects brain circuitries related to mental illness.
AB  - CONTEXT: The CACNA1C gene (alpha-1C subunit of the L-type voltage-gated calcium
      channel) has been identified as a risk gene for bipolar disorder and
      schizophrenia, but the mechanism of association has not been explored. OBJECTIVE:
      To identify the neural system mechanism that explains the genetic association
      between the CACNA1C gene and psychiatric illness using neuroimaging and human
      brain expression. DESIGN: We used blood oxygenation level-dependent (BOLD)
      functional magnetic resonance imaging (fMRI) to measure brain activation in
      circuitries related to bipolar disorder and schizophrenia by comparing CACNA1C
      genotype groups among healthy subjects. We tested the effect of genotype on
      messenger RNA (mRNA) levels of CACNA1C in postmortem human brain. A case-control
      analysis was used to determine the association of CACNA1C genotype with
      schizophrenia. SETTING: National Institutes of Health Clinical Center. PATIENTS:
      Healthy men and women of white race/ethnicity participated in the fMRI study.
      Postmortem samples from normal human brains were used for the brain expression
      study. Patients with schizophrenia and healthy subjects were used in the case
      control analysis. MAIN OUTCOME MEASURES: BOLD fMRI, mRNA levels in postmortem
      brain samples, and genetic association with schizophrenia. RESULTS: The risk
      associated single-nucleotide polymorphism (SNP rs1006737) in CACNA1C predicted
      increased hippocampal activity during emotional processing (P = .001 uncorrected,
      P((false recovery rate [FDR])) = .05, z = 3.20) and increased prefrontal activity
      during executive cognition (P = 2.8e-05 uncorrected, P(FDR) = .01, z = 4.03). The
      risk-associated SNP also predicted increased expression of CACNA1C mRNA in human
      brain (P = .002). CACNA1C was associated with schizophrenia in our case-control
      sample (odds ratio, 1.77; P = .03). CONCLUSIONS: The risk-associated SNP in
      CACNA1C maps to circuitries implicated in genetic risk for bipolar disorder and
      schizophrenia. Its effects in human brain expression implicate a molecular and
      neural system mechanism for the clinical genetic association.

PMID- 20819990
TI  - Reduced brain white matter integrity in trichotillomania: a diffusion tensor
      imaging study.
AB  - CONTEXT: Trichotillomania is an Axis I disorder characterized by repetitive,
      pathological hair pulling. OBJECTIVE: To assess the integrity of white matter
      tracts in subjects with the disorder. DESIGN: Between-group comparison using
      permutation cluster analysis, with stringent correction for multiple comparisons.
      SETTING: Academic psychiatry department. PARTICIPANTS: Eighteen volunteers
      meeting DSM-IV criteria for trichotillomania and 19 healthy control subjects.
      MAIN OUTCOME MEASURES: Fractional anisotropy (measured using diffusion tensor
      imaging), trichotillomania disease severity (Massachusetts General Hospital
      Hairpulling Scale score), and dysphoria (Montgomery-Asberg Depression Rating
      Scale score). RESULTS: Subjects with trichotillomania exhibited significantly
      reduced fractional anisotropy in anterior cingulate, presupplementary motor area,
      and temporal cortices. Fractional anisotropy did not correlate significantly with
      trichotillomania disease severity or depressive mood scores. CONCLUSIONS: These
      data implicate disorganization of white matter tracts involved in motor habit
      generation and suppression, along with affective regulation, in the
      pathophysiology of trichotillomania.

PMID- 20819989
TI  - Enlargement of thalamic nuclei in Tourette syndrome.
AB  - CONTEXT: The basal ganglia and thalamus together connect in parallel closed-loop
      circuits with the cortex. Previous imaging studies have shown modifications of
      the basal ganglia and cortical targets in individuals with Tourette syndrome
      (TS), but less is known regarding the role of the thalamus in TS pathogenesis.
      OBJECTIVE: To study the morphological features of the thalamus in children and
      adults with TS. DESIGN: A cross-sectional, case-control study using anatomical
      magnetic resonance imaging. SETTING: University research center. PARTICIPANTS:
      The 283 participants included 149 with TS and 134 normal control individuals aged
      6 to 63 years. MAIN OUTCOME MEASURES: Conventional volumes and measures of
      surface morphology of the thalamus. RESULTS: Analyses of conventional volumes and
      surface morphology were consistent in demonstrating an enlargement in TS-affected
      thalami. Overall volumes were 5% larger in the group composed of children and
      adults with TS. Statistical maps of surface contour demonstrated enlargement over
      the lateral thalamus. Post hoc testing indicated that differences in IQ, comorbid
      illnesses, and medication use did not account for these findings. CONCLUSIONS:
      Morphological abnormalities in the thalamus, together with the disturbances
      reported in the sensorimotor cortex, striatum, and globus pallidus, support the
      hypothesis of a circuitwide disorder within motor pathways in TS. The
      connectivity and function of the numerous and diverse thalamic nuclei within
      cortical-subcortical circuits constitute an anatomical crossroad wherein
      enlargement of motor nuclei may represent activity-dependent hypertrophy within
      this component of cortical-subcortical motor circuits, or an adaptive response
      within a larger putative compensatory system that could thereby directly modulate
      activity in motor circuits to attenuate the severity of tics.

PMID- 20819991
TI  - Antiepileptic drugs and suicide attempts in patients with bipolar disorder.

PMID- 20819992
TI  - Pearls & Oy-sters: electroconvulsive therapy in anti-NMDA receptor encephalitis.

PMID- 20819993
TI  - Teaching NeuroImages: transient epileptic amnesia.

PMID- 20819995
TI  - The ischemic penumbra: from celestial body to imaging technology.

PMID- 20819996
TI  - Clicking the eye muscles? The diagnostic value of sound-evoked vestibular
      reflexes.

PMID- 20819997
TI  - Brain choline concentration. Early quantitative marker of ischemia and infarct
      expansion?
AB  - OBJECTIVE: Better prediction of tissue prognosis in acute stroke might improve
      treatment decisions. We hypothesized that there are metabolic ischemic
      disturbances measurable noninvasively by proton magnetic resonance spectroscopy
      ((1)H MRS) that occur earlier than any structural changes visible on diffusion
      tensor imaging (DTI), which may therefore serve for territorial identification of
      tissue at risk. METHODS: We performed multivoxel (1)H MRS plus DTI within a
      maximum of 26 hours, and DTI at 3-7 days, after ischemic stroke. We compared
      choline, lactate, N-acetylaspartate, and creatine concentrations in normal
      appearing voxels that became infarcted (infarct expansion) with normal-appearing
      voxels around the infarct that remained "healthy" (nonexpansion) on follow-up
      DTI. Each infarct expansion voxel was additionally classified as either complete
      infarct expansion (infarcted tissue on follow-up DTI covered > or =50% of the
      voxel) or partial infarct expansion (<50% of voxel). RESULTS: In 31 patients (NIH
      Stroke Scale score 0-28), there were 108 infarct nonexpansion voxels and 113
      infarct expansion voxels (of which 80 were complete expansion and 33 partial
      expansion voxels). Brain choline concentration increased for each change in
      expansion category from nonexpansion, via partial expansion to complete expansion
      (2,423, 3,843, 4,158 IU; p < 0.05). Changes in lactate, N-acetylaspartate, and
      creatine concentrations in expansion category were insignificant although for
      lactate there was a tendency to such association. CONCLUSIONS: Choline
      concentration measurable with (1)H MRS was elevated in peri-ischemic normal
      appearing brain that became infarcted by 3-7 days. The degree of elevation was
      associated with the amount of infarct expansion. (1)H MRS might identify DTI
      normal-appearing tissue at risk of conversion to infarction in early stroke.

PMID- 20819998
TI  - Testosterone modifies the effect of APOE genotype on hippocampal volume in middle
      aged men.
AB  - BACKGROUND: The APOE epsilon4 allele is an established risk factor for Alzheimer
      disease (AD), yet findings are mixed for how early its effects are manifest. One
      reason for the mixed results could be the presence of interaction effects with
      other AD risk factors. Increasing evidence indicates that testosterone may play a
      significant role in the development of AD. The aim of the present study was to
      examine the potential interaction of testosterone and APOE genotype with respect
      to hippocampal volume in middle age. METHODS: Participants were men from the
      Vietnam Era Twin Study of Aging (n = 375). The mean age was 55.9 years (range 51
      59). Between-group comparisons were performed utilizing a hierarchical linear
      mixed model that adjusted for the nonindependence of twin data. RESULTS: A
      significant interaction was observed between testosterone and APOE genotype
      (epsilon4-negative vs epsilon4-positive). Those with both low testosterone (> or
      =1 SD below the mean) and an epsilon4-positive status had the smallest
      hippocampal volumes, although comparisons with normal testosterone groups were
      not significant. However, individuals with low testosterone and epsilon4-negative
      status had significantly larger hippocampal volumes relative to all other groups.
      A main effect of APOE genotype on hippocampal volume was observed, but only when
      the APOE-by-testosterone interaction was present. CONCLUSIONS: These findings
      demonstrate an interaction effect between testosterone and the APOE epsilon4
      allele on hippocampal volume in middle-aged men, and they may suggest 2 low
      testosterone subgroups. Furthermore, these results allude to potential gene-gene
      interactions between APOE and either androgen receptor polymorphisms or genes
      associated with testosterone production.

PMID- 20819999
TI  - Distinct cerebral perfusion patterns in FTLD and AD.
AB  - OBJECTIVE: We examined the utility of distinguishing between patients with
      frontotemporal lobar degeneration (FTLD) and Alzheimer disease (AD) using
      quantitative cerebral blood flow (CBF) imaging with arterial spin labeled (ASL)
      perfusion MRI. METHODS: Forty-two patients with FTLD and 18 patients with AD,
      defined by autopsy or CSF-derived biomarkers for AD, and 23 matched controls were
      imaged with a continuous ASL method to quantify CBF maps covering the entire
      brain. RESULTS: Patients with FTLD and AD showed distinct patterns of
      hypoperfusion and hyperperfusion. Compared with controls, patients with FTLD
      showed significant hypoperfusion in regions of the frontal lobe bilaterally, and
      hyperperfusion in posterior cingulate and medial parietal/precuneus regions.
      Compared with controls, patients with AD showed significant hypoperfusion in the
      medial parietal/precuneus and lateral parietal cortex, and hyperperfusion in
      regions of the frontal lobe. Direct comparison of patient groups showed
      significant inferior, medial, and dorsolateral frontal hypoperfusion in FTLD, and
      significant hypoperfusion in bilateral lateral temporal-parietal and medial
      parietal/precuneus regions in AD. CONCLUSIONS: Doubly dissociated areas of
      hypoperfusion in FTLD and AD are consistent with areas of significant
      histopathologic burden in these groups. ASL is a potentially useful biomarker for
      distinguishing patients with these neurodegenerative diseases.

PMID- 20820000
TI  - Prevalence of mild cognitive impairment is higher in men. The Mayo Clinic Study
      of Aging.
AB  - OBJECTIVE: We investigated the prevalence of mild cognitive impairment (MCI) in
      Olmsted County, MN, using in-person evaluations and published criteria. METHODS:
      We evaluated an age- and sex-stratified random sample of Olmsted County residents
      who were 70-89 years old on October 1, 2004, using the Clinical Dementia Rating
      Scale, a neurologic evaluation, and neuropsychological testing to assess 4
      cognitive domains: memory, executive function, language, and visuospatial skills.
      Information for each participant was reviewed by an adjudication panel and a
      diagnosis of normal cognition, MCI, or dementia was made using published
      criteria. RESULTS: Among 1,969 subjects without dementia, 329 subjects had MCI,
      with a prevalence of 16.0% (95% confidence interval [CI] 14.4-17.5) for any MCI,
      11.1% (95% CI 9.8-12.3) for amnestic MCI, and 4.9% (95% CI 4.0-5.8) for
      nonamnestic MCI. The prevalence of MCI increased with age and was higher in men.
      The prevalence odds ratio (OR) in men was 1.54 (95% CI 1.21-1.96; adjusted for
      age, education, and nonparticipation). The prevalence was also higher in subjects
      who never married and in subjects with an APOE epsilon3epsilon4 or
      epsilon4epsilon4 genotype. MCI prevalence decreased with increasing number of
      years of education (p for linear trend <0.0001). CONCLUSIONS: Our study suggests
      that approximately 16% of elderly subjects free of dementia are affected by MCI,
      and amnestic MCI is the most common type. The higher prevalence of MCI in men may
      suggest that women transition from normal cognition directly to dementia at a
      later age but more abruptly.

PMID- 20820001
TI  - Congenital muscular dystrophies with cognitive impairment. A population study.
AB  - BACKGROUND: Cognitive impairment has been reported in a significant proportion of
      patients with congenital muscular dystrophies (CMD), generally associated with
      brain changes. OBJECTIVES: The aim of this study was to establish 1) the overall
      prevalence of CMD and cognitive impairment in the Italian population; 2) the
      frequency of individual genetically defined forms; and 3) the presence of
      distinct phenotypes not associated with mutations in the known genes. METHODS: We
      included all patients with CMD and cognitive impairment followed in all the
      Italian tertiary neuromuscular centers. Clinical, brain MRI, and morphologic data
      were collected. Genetic screening of the known genes was performed according to
      clinical and muscle biopsy findings. RESULTS: Ninety-two of the 160 (58%)
      patients with CMD followed in our centers had cognitive impairment. alpha
      Dystroglycan (alpha-DG) reduction on muscle biopsy was found in 73/92 (79%), with
      42/73 carrying mutations in the known genes. Another 6/92 (7%) showed a laminin
      alpha2 deficiency on muscle biopsy and 5 of the 6 carried mutations in LAMA2. The
      remaining 13/92 (14%) patients had normal alpha-DG and laminin alpha2 expression
      on muscle. CONCLUSIONS: This is the first population study establishing the
      prevalence of CMD and cognitive impairment and providing a classification on the
      basis of clinical, MRI, and genetic findings. We also showed that cognitive
      impairment was not always associated with alpha-DG or laminin alpha2 reduction or
      with structural brain changes.

PMID- 20820002
TI  - Safety and efficacy of natalizumab in children with multiple sclerosis.
AB  - OBJECTIVE: To describe the effect of natalizumab in the treatment of subjects
      with active multiple sclerosis (MS) treated before the age of 18 years. METHODS:
      Nineteen pediatric subjects with MS (mean age 14.6 +/- 2.2 years, mean number of
      attacks 5.2 +/- 1.9 during the pretreatment phase of 27.7 +/- 19.7 months, median
      pretreatment Expanded Disability Status Scale score [EDSS] 2.5, range 1.0-5.0)
      were treated with natalizumab at the dose of 300 mg every 28 days. After
      treatment initiation, patients were reassessed clinically every month; brain MRI
      was performed at baseline and every 6 months. RESULTS: Patients received a median
      number of 15 infusions (range 6-26). A transient reversible worsening of
      preexisting symptoms occurred in 1 subject during and following the first
      infusion. All the patients remained relapse-free during the whole follow-up. The
      median EDSS decreased from 2.5 to 2.0 at the last visit (p < 0.001). EDSS
      remained stable in 5 cases, decreased by at least 0.5 point in 6 cases, and
      decreased by at least 1 point in 8 cases. At baseline, the mean number of
      gadolinium-enhancing lesions was 4.1 (range 1-20). During the follow-up, no
      gadolinium-enhancing lesions were detected (p = 0.008); 3 patients developed new
      T2-visible lesions at month 6 scan but the overall number of T2 lesions remained
      stable during the subsequent follow-up. Transient and mild side effects occurred
      in 8 patients. CONCLUSIONS: Natalizumab was well-tolerated in all subjects. A
      strong suppression of disease activity was observed in all subjects during the
      follow-up. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that
      natalizumab, 300 mg IV once every 28 days, decreased EDSS scores in pediatric
      patients with MS over a mean treatment period of 15.2 months.

PMID- 20820003
TI  - Hydrocephalus in adults with community-acquired bacterial meningitis.
AB  - OBJECTIVE: To evaluate the occurrence, treatment, and outcome of hydrocephalus
      complicating community-acquired bacterial meningitis in adults. METHODS: Case
      series from a prospective nationwide cohort study from Dutch hospitals from 2006
      to 2009. RESULTS: Hydrocephalus was diagnosed in 26 of 577 episodes (5%) and was
      classified as communicating hydrocephalus in all but 1 patient. The majority of
      patients (69%) presented with hydrocephalus on admission. Most common causative
      bacteria were Streptococcus pneumoniae (in 14 patients, 54%) and Listeria
      monocytogenes (in 4 patients, 15%). Thirteen patients died (50%) and 18 had an
      unfavorable outcome (69%). Hydrocephalus was an independent predictor of death in
      a multivariate analysis (odds ratio 7.81, 95% confidence interval 2.91-20.8). Six
      patients underwent an intervention: 2 patients (8%) had serial lumbar punctures;
      4 patients (15%) underwent external ventricular CSF catheter placement. Median
      time from diagnosis of hydrocephalus to CSF shunting was 12 hours (range 0-4
      days). All patients who underwent CSF shunting died or had a poor outcome.
      CONCLUSIONS: Hydrocephalus complicates community-acquired bacterial meningitis in
      5% of adult cases and is associated with high fatality rates. A minority of
      patients underwent neurosurgery and outcome was uniformly poor in these patients.

PMID- 20820004
TI  - Challenge of the unknown. A systematic review of acute encephalitis in non
      outbreak situations.
AB  - BACKGROUND: The threat of emerging infections and recognition of novel immune
      mediated forms of encephalitis has raised the profile of this condition in recent
      years. Incidence is poorly defined and most cases have an unknown cause. There is
      currently much interest in identification of new microbial agents of
      encephalitis, but no work has investigated systematically reasons for lack of
      pathogen identification in studies. METHODS: We systematically reviewed published
      literature on incidence and etiology of encephalitis in non-outbreak settings and
      explored possible explanations for the large number of cases of unknown etiology.
      RESULTS: Annual incidence ranged from 0.07 to 12.6 cases per 100,000 population
      with an evident decrease over time (p = 0.01). The proportion of cases with
      unknown etiology was high across studies (>50% in 26 of 41 studies), with strong
      evidence of heterogeneity in study findings (p < 0.001). Our meta-regression
      identified study period, setting, and subsyndrome to be the main contributors to
      between-study variation, rather than methodologic factors such as study design,
      case definitions, sample types, and testing strategies. CONCLUSIONS: Our findings
      support the hypothesis that new and emerging infectious agents, or new forms of
      immune-mediated encephalitis, may be responsible for cases currently of unknown
      cause and encourage the ongoing global effort to identify these. Our review
      highlights research areas that might lead to a better understanding of the causes
      of encephalitis and ultimately reduce the morbidity and mortality associated with
      this devastating condition.

PMID- 20820005
TI  - Click-evoked vestibulo-ocular reflex distinguishes posterior from superior canal
      dehiscence.

PMID- 20820006
TI  - Lipoma of the corpus callosum and mirror writing.

PMID- 20820007
TI  - Neuronal voltage-gated calcium channels: brief overview of their function and
      clinical implications in neurology.

PMID- 20820008
TI  - Sweeping up health reform's piles of unfinished business.

PMID- 20820009
TI  - Averting medical malpractice lawsuits: effective medicine--or inadequate cure?

PMID- 20820010
TI  - National costs of the medical liability system.
AB  - Concerns about reducing the rate of growth of health expenditures have reignited
      interest in medical liability reforms and their potential to save money by
      reducing the practice of defensive medicine. It is not easy to estimate the costs
      of the medical liability system, however. This article identifies the various
      components of liability system costs, generates national estimates for each
      component, and discusses the level of evidence available to support the
      estimates. Overall annual medical liability system costs, including defensive
      medicine, are estimated to be $55.6 billion in 2008 dollars, or 2.4 percent of
      total health care spending.

PMID- 20820011
TI  - Low costs of defensive medicine, small savings from tort reform.
AB  - In this paper we present the costs of defensive medicine in thirty-five clinical
      specialties to determine whether malpractice liability reforms would greatly
      reduce health care costs. Defensive medicine includes tests and procedures
      ordered by physicians principally to reduce perceived threats of medical
      malpractice liability. The practice is commonly assumed to increase health care
      costs. The results of studies of the costs of defensive medicine have been
      inconsistent. We found that estimated savings resulting from a 10 percent decline
      in medical malpractice premiums would be less than 1 percent of total medical
      care costs in every specialty. These savings are lower than most previous
      estimates, and they suggest that the presumed impact of tort reform on health
      care costs may be overstated.

PMID- 20820012
TI  - Physicians' fears of malpractice lawsuits are not assuaged by tort reforms.
AB  - Physicians contend that the threat of malpractice lawsuits forces them to
      practice defensive medicine, which in turn raises the cost of health care. This
      argument underlies efforts to change malpractice laws through legislative tort
      reform. We evaluated physicians' perceptions about malpractice claims in states
      where more objective indicators of malpractice risk, such as malpractice
      premiums, varied considerably. We found high levels of malpractice concern among
      both generalists and specialists in states where objective measures of
      malpractice risk were low. We also found relatively modest differences in
      physicians' concerns across states with and without common tort reforms. These
      results suggest that many policies aimed at controlling malpractice costs may
      have a limited effect on physicians' malpractice concerns.

PMID- 20820013
TI  - Adopting a surgical safety checklist could save money and improve the quality of
      care in U.S. hospitals.
AB  - Use of the World Health Organization's Surgical Safety Checklist has been
      associated with a significant reduction in major postoperative complications
      after inpatient surgery. We hypothesized that implementing the checklist in the
      United States would generate cost savings for hospitals. We performed a decision
      analysis comparing implementation of the checklist to existing practice in U.S.
      hospitals. In a hospital with a baseline major complication rate after surgery of
      at least 3 percent, the checklist generates cost savings once it prevents at
      least five major complications. Using the checklist would both save money and
      improve the quality of care in hospitals throughout the United States.

PMID- 20820014
TI  - Changing the culture in medical education to teach patient safety.
AB  - In 1999 a seminal Institute of Medicine report estimated that preventable medical
      errors accounted for 44,000-98,000 patient deaths annually in U.S. hospitals. In
      response to this problem, the nation's medical schools, teaching hospitals, and
      health systems recognized that achieving greater patient safety requires more
      than a brief course in an already crowded medical school curriculum. It requires
      a fundamental culture change across all phases of medical education. This
      includes graduate medical education, which is already teaching the next
      generation of physicians to approach patient safety in a new way. In this paper
      the authors explore five factors critical to transforming the culture for patient
      safety and reflect on one real-world example at the University of North Carolina
      School of Medicine.

PMID- 20820015
TI  - Why diagnostic errors don't get any respect--and what can be done about them.
AB  - The first decade of the patient safety movement achieved some real gains, focused
      as it was on adverse events amenable to systemwide solutions, such as infections
      associated with health care and medication errors. However, diagnostic errors,
      although common and often serious, have not received comparable attention. They
      are challenging to measure and less amenable to systemwide solutions.
      Furthermore, it is difficult to hold hospitals accountable, since diagnostic
      errors usually result from cognitive mistakes on the part of one or more members
      of the medical staff. Health information technology, better training, and
      increasing acknowledgment of the problem hold some promise. As approaches to
      measuring, preventing, and mitigating harm from diagnostic errors are proven to
      work, it will be important to integrate these approaches into policy initiatives
      to improve patient safety.

PMID- 20820016
TI  - The flaws in state 'apology' and 'disclosure' laws dilute their intended impact
      on malpractice suits.
AB  - Apologies are rare in the medical world, where health care providers fear that
      admissions of guilt or expressions of regret could be used by plaintiffs in
      malpractice lawsuits. Nevertheless, some states are moving toward giving health
      care providers legal protection so that they feel free to apologize to patients
      for a medical mistake. Advocates believe that these laws are beneficial for
      patients and providers. However, our analysis of "apology" and "disclosure" laws
      in thirty-four states and the District of Columbia finds that most of the laws
      have major shortcomings. These may actually discourage comprehensive disclosures
      and apologies and weaken the laws' impact on malpractice suits. Many could be
      resolved by improved statutory design and communication of new legal requirements
      and protections.

PMID- 20820017
TI  - Where Americans get acute care: increasingly, it's not at their doctor's office.
AB  - Historically, general practitioners provided first-contact care in the United
      States. Today, however, only 42 percent of the 354 million annual visits for
      acute care--treatment for newly arising health problems--are made to patients'
      personal physicians. The rest are made to emergency departments (28 percent),
      specialists (20 percent), or outpatient departments (7 percent). Although fewer
      than 5 percent of doctors are emergency physicians, they handle a quarter of all
      acute care encounters and more than half of such visits by the uninsured. Health
      reform provisions in the Patient Protection and Affordable Care Act that advance
      patient-centered medical homes and accountable care organizations are intended to
      improve access to acute care. The challenge for reform will be to succeed in the
      current, complex acute care landscape.

PMID- 20820018
TI  - Many emergency department visits could be managed at urgent care centers and
      retail clinics.
AB  - Americans seek a large amount of nonemergency care in emergency departments,
      where they often encounter long waits to be seen. Urgent care centers and retail
      clinics have emerged as alternatives to the emergency department for nonemergency
      care. We estimate that 13.7-27.1 percent of all emergency department visits could
      take place at one of these alternative sites, with a potential cost savings of
      approximately $4.4 billion annually. The primary conditions that could be treated
      at these sites include minor acute illnesses, strains, and fractures. There is
      some evidence that patients can safely direct themselves to these alternative
      sites. However, more research is needed to ensure that care of equivalent quality
      is provided at urgent care centers and retail clinics compared to emergency
      departments.

PMID- 20820019
TI  - A plan to reduce emergency room 'boarding' of psychiatric patients.
AB  - Overcrowded U.S. emergency rooms have become a place of last resort for
      psychiatric patients. Psychiatric boarding, defined as psychiatric patients'
      waiting in hallways or other emergency room areas for inpatient beds, is a
      serious problem nationwide. Boarding consumes scarce emergency room resources and
      prolongs the amount of time that all patients must spend waiting for services. It
      is often the result of an inability to gain timely access to community-based
      care. As policy makers implement the new health reform law, improving access and
      continuity of community mental health care through health homes must be a
      priority. We present a seven-point plan to address psychiatric boarding.

PMID- 20820020
TI  - Copayments did not reduce medicaid enrollees' nonemergency use of emergency
      departments.
AB  - Eager to reduce unnecessary use of hospital emergency departments by Medicaid
      enrollees, states are increasingly implementing cost sharing for nonemergency
      visits. This paper uses monthly data from the 2001-2006 Medical Expenditure Panel
      Surveys (MEPS) to examine how changes in nine states' copayment policies
      influence enrollees' use of emergency departments. The results suggest that
      requiring copayments for nonemergency visits did not decrease emergency
      department use by Medicaid enrollees. Future research should examine more closely
      the effects at the state level and investigate whether these copayments affected
      the use of other services, such as hospitalizations or visits to physicians by
      Medicaid enrollees.

PMID- 20820021
TI  - Why lowering health costs should be a key adjunct to slowing health spending
      growth.
AB  - If U.S. health care spending growth continues unchecked, the nation will have far
      less in the future to purchase other essentials, including education,
      infrastructure, and consumer goods. The point at which nonhealth spending could
      begin a precipitous decline was previously projected in a paper by Michael
      Chernew and colleagues to be 2050, unless the rate of health cost growth can be
      lowered (that is, "bending the curve"). This paper evaluates alternative
      approaches. First, it looks at the effect on health and nonhealth spending of a
      one-time reduction in health costs--for example, through a sharp reduction in
      overuse of medical services in higher-cost regions of the country. It concludes
      that a one-time reduction in the range of 20-35 percent would delay Chernew's
      projected decline in nonhealth spending by ten to twenty years. Second, it looks
      at the effect of combining up-front spending reductions of this size with a
      longer-range cut in the rate of growth of health spending from 2 percentage
      points to 1.5 percentage points annually. It finds that this scenario would
      postpone a major drop in nonhealth spending almost until the twenty-second
      century. The paper argues that substantial up-front reductions in health spending
      are therefore worth pursuing to protect the nation's long-term economic growth.

PMID- 20820022
TI  - Greater use of preventive services in U.S. health care could save lives at little
      or no cost.
AB  - There is broad debate over whether preventive health services save money or
      represent a good investment. This paper analyzes the estimated cost of adopting a
      package of twenty proven preventive services--including tobacco cessation
      screening, alcohol abuse screening, and daily aspirin use--against the estimated
      savings that could be generated. We find that greater use of proven clinical
      preventive services in the United States could avert the loss of more than two
      million life-years annually. What's more, increasing the use of these services
      from current levels to 90 percent in 2006 would result in total savings of $3.7
      billion, or 0.2 percent of U.S. personal health care spending. These findings
      suggest that policy makers should pursue options that move the nation toward
      greater use of proven preventive services.

PMID- 20820023
TI  - Paying physicians by capitation: is the past now prologue?
AB  - In the 1980s and 1990s, physician capitation-in which participating physicians
      received a fixed sum for each insured patient regardless of how much care the
      patient received-was widely touted as a way to restrain costs and encourage more
      efficient care. Capitation remained prevalent in markets with a substantial
      health maintenance organization (HMO) presence but virtually disappeared
      elsewhere as HMO enrollment declined. By 2007, only 7 percent of all physician
      office visits were covered under capitation arrangements. Given this history,
      markets that now lack infrastructure to handle physician risk sharing will
      probably be challenged by current proposals for payment reform, many of which
      incorporate components of capitation.

PMID- 20820024
TI  - How health plans, health systems, and others in the private sector can stimulate
      'meaningful use'.
AB  - Provisions of the American Recovery and Reinvestment Act authorize incentive
      payments to hospitals and clinicians who become "meaningful users" of health
      information technology (IT). We argue that various private-sector entities-
      commercial payers, employers, consumer groups, health care ratings organizations,
      large provider organizations, and regulatory bodies--can further accelerate
      health IT adoption by implementing strategies that are complementary to the
      Medicare and Medicaid incentive programs. This paper describes these strategies
      and potential approaches to implementation.

PMID- 20820025
TI  - Beacon communities aim to use health information technology to transform the
      delivery of care.
AB  - The Beacon Community Program, authorized under the 2009 American Recovery and
      Reinvestment Act (ARRA), aims to demonstrate the potential for health information
      technology to enable local improvements in health care quality, cost efficiency,
      and population health. If successful, these communitywide efforts will yield
      important lessons that will assist other communities seeking to harness
      technology to achieve and sustain health care improvements. This paper highlights
      key programmatic details that reflect the meaningful use of technology in the
      fifteen Beacon communities. It describes the innovations they propose and
      provides insight into current and future challenges.

PMID- 20820026
TI  - Grand Junction, Colorado: how a community drew on its values to shape a superior
      health system.
AB  - For the past decade, the high-quality, relatively low-cost health care delivered
      in Grand Junction, Colorado, has led that community to outperform most others in
      the United States. Medicare patients in Grand Junction have fewer
      hospitalizations, shorter hospitalizations, and lower mortality rates after
      hospitalization than do Medicare patients in comparison hospitals. Effective,
      efficient care is delivered in Grand Junction through separate, self-governing
      organizations that perceive health care as a community resource. This article
      describes how the various stakeholders in Grand Junction have addressed problems
      and set standards for the system. The lessons could apply to broader health
      reform efforts in communities around the country.

PMID- 20820027
TI  - How the stars aligned to make Grand Junction a success.

PMID- 20820028
TI  - Fighting antibiotic resistance: marrying new financial incentives to meeting
      public health goals.
AB  - The world faces a worsening public health crisis: A growing number of bacteria
      are resistant to available antibiotics. Yet there are few new antibiotics in the
      development pipeline to take the place of these increasingly ineffective drugs.
      We review a number of proposals intended to bolster drug development, including
      such financial incentives for pharmaceutical manufacturers as extending the
      effective patent life for new antibiotics. However, such strategies directly
      conflict with the clear need to reduce unnecessary antibiotic prescriptions and
      could actually increase prescription use. As an alternative, we recommend a two
      prong, "integrated" strategy. This would increase reimbursement for the
      appropriate, evidence-based use of antibiotics that also met specific public
      health goals--such as reducing illness levels while limiting antibiotic
      resistance.

PMID- 20820029
TI  - Medical-legal partnerships: transforming primary care by addressing the legal
      needs of vulnerable populations.
AB  - Health care is undermined when patients don't receive the benefit of laws
      intended to address social determinants of health, such as housing and food.
      Medical-legal partnerships, which now exist in more than 200 clinical sites in
      the United States, integrate lawyers into health care to address legal problems
      that create and perpetuate poor health. This paper describes how such medical
      legal partnerships can change clinical systems--for example, by adding legal form
      letters to electronic health records to help low-income patients rectify
      substandard housing conditions. We recommend the integration of medical-legal
      partnerships into federal health care programs.

PMID- 20820030
TI  - Public reporting drove quality gains at nursing homes.
AB  - Public reporting of the quality of care delivered in hospitals and nursing homes
      is thought to foster improvements in care. When information is available,
      consumers may choose high-quality providers. That choice, in turn, may stimulate
      providers to improve quality as a way to attract a larger share of the market.
      However, these assumptions have gone largely untested. We examined short-stay
      care provided at 8,137 nursing homes after the Nursing Home Compare public
      reporting requirements went into effect in 2002. We found that quality improved
      both because consumers chose higher-quality nursing homes and because providers
      improved the care they delivered. These findings support the continued use of
      public reporting to improve quality.

PMID- 20820031
TI  - Aging and the inaccessible city.

PMID- 20820032
TI  - GrantWatch outcomes. Health reform.

PMID- 20820033
TI  - Transforming patients into consumers of health care.

PMID- 20820034
TI  - Medical homes led by nurses.

PMID- 20820035
TI  - Summaries for patients. Patients' and cardiologists' beliefs about a common heart
      procedure.

PMID- 20820036
TI  - In the clinic. Acute sinusitis.
AB  - This issue provides a clinical overview of acute sinusitis focusing on
      prevention, diagnosis, treatment, practice improvement, and patient information.
      Readers can complete the accompanying CME quiz for 1.5 credits. Only ACP members
      and individual subscribers can access the electronic features of In the Clinic.
      Non-subscribers who wish to access this issue of In the Clinic can elect "Pay for
      View." Subscribers can receive 1.5 category 1 CME credits by completing the CME
      quiz that accompanies this issue of In the Clinic. The content of In the Clinic
      is drawn from the clinical information and education resources of the American
      College of Physicians (ACP), including PIER (Physicians' Information and
      Education Resource) and MKSAP (Medical Knowledge and Self Assessment Program).
      Annals of Internal Medicine editors develop In the Clinic from these primary
      sources in collaboration with the ACP's Medical Education and Publishing division
      and with assistance of science writers and physician writers. Editorial
      consultants from PIER and MKSAP provide expert review of the content. Readers who
      are interested in these primary resources for more detail can consult
      www.acponline.org, http://pier.acponline.org, and other resources referenced
      within each issue of In the Clinic.

PMID- 20820037
TI  - Variations in the promoter region of the glutaminase gene and the development of
      hepatic encephalopathy in patients with cirrhosis: a cohort study.
AB  - BACKGROUND: Hepatic encephalopathy is a major complication of cirrhosis and is
      associated with a poor prognosis. OBJECTIVE: To identify mutations in the gene
      sequence for glutaminase in humans that could be responsible for the development
      of hepatic encephalopathy in patients with cirrhosis. DESIGN: Cohort study.
      SETTING: Outpatient clinics in 6 Spanish hospitals. PATIENTS: 109 consecutive
      patients with cirrhosis in the estimation cohort, 177 patients in the validation
      cohort, and 107 healthy control participants. MEASUREMENTS: Patients were
      followed every 3 or 6 months until the development of hepatic encephalopathy or
      liver transplantation, death, or the end of the study. RESULTS: The genetic
      analyses showed that glutaminase TACC and CACC haplotypes were linked to the risk
      for overt hepatic encephalopathy. Mutation scanning of the glutaminase gene
      identified a section in the promoter region where base pairs were repeated (a
      microsatellite). Over a mean follow-up of 29.6 months, hepatic encephalopathy
      occurred in 28 patients (25.7%) in the estimation cohort. Multivariable Cox
      models were used to determine the following independent predictors: Child
      Turcotte-Pugh stage (hazard ratio [HR], 1.6 [95% CI, 1.29 to 1.98]; P = 0.001),
      minimal hepatic encephalopathy (HR, 3.17 [CI, 1.42 to 7.09]; P = 0.006), and
      having 2 long alleles of the microsatellite (HR, 3.12 [CI, 1.39 to 7.02]; P =
      0.006). The association between 2 long alleles of the microsatellite and overt
      hepatic encephalopathy was confirmed in a validation cohort (HR, 2.1 [CI, 1.17 to
      3.79]; P = 0.012). Functional studies showed higher luciferase activity in cells
      transfected with the long form of the microsatellite, which suggests that the
      long microsatellite enhances glutaminase transcriptional activity. LIMITATION:
      Other genes and allelic variants might be involved in the clinical expression of
      hepatic encephalopathy. CONCLUSION: This study identifies a genetic factor that
      is associated with development of hepatic encephalopathy in patients with
      cirrhosis. PRIMARY FUNDING SOURCE: Instituto de Salud Carlos III, Spanish
      Ministry of Health.

PMID- 20820038
TI  - Low-carbohydrate diets and all-cause and cause-specific mortality: two cohort
      studies.
AB  - BACKGROUND: Data on the long-term association between low-carbohydrate diets and
      mortality are sparse. OBJECTIVE: To examine the association of low-carbohydrate
      diets with mortality during 26 years of follow-up in women and 20 years in men.
      DESIGN: Prospective cohort study of women and men who were followed from 1980
      (women) or 1986 (men) until 2006. Low-carbohydrate diets, either animal-based
      (emphasizing animal sources of fat and protein) or vegetable-based (emphasizing
      vegetable sources of fat and protein), were computed from several validated food
      frequency questionnaires assessed during follow-up. SETTING: Nurses' Health Study
      and Health Professionals' Follow-up Study. PARTICIPANTS: 85 168 women (aged 34 to
      59 years at baseline) and 44 548 men (aged 40 to 75 years at baseline) without
      heart disease, cancer, or diabetes. MEASUREMENTS: Investigators documented 12 555
      deaths (2458 cardiovascular-related and 5780 cancer-related) in women and 8678
      deaths (2746 cardiovascular-related and 2960 cancer-related) in men. RESULTS: The
      overall low-carbohydrate score was associated with a modest increase in overall
      mortality in a pooled analysis (hazard ratio [HR] comparing extreme deciles, 1.12
      [95% CI, 1.01 to 1.24]; P for trend = 0.136). The animal low-carbohydrate score
      was associated with higher all-cause mortality (pooled HR comparing extreme
      deciles, 1.23 [CI, 1.11 to 1.37]; P for trend = 0.051), cardiovascular mortality
      (corresponding HR, 1.14 [CI, 1.01 to 1.29]; P for trend = 0.029), and cancer
      mortality (corresponding HR, 1.28 [CI, 1.02 to 1.60]; P for trend = 0.089). In
      contrast, a higher vegetable low-carbohydrate score was associated with lower all
      cause mortality (HR, 0.80 [CI, 0.75 to 0.85]; P for trend </= 0.001) and
      cardiovascular mortality (HR, 0.77 [CI, 0.68 to 0.87]; P for trend < 0.001).
      LIMITATIONS: Diet and lifestyle characteristics were assessed with some degree of
      error. Sensitivity analyses indicated that results were probably not
      substantively affected by residual confounding or an unmeasured confounder.
      Participants were not a representative sample of the U.S. population. CONCLUSION:
      A low-carbohydrate diet based on animal sources was associated with higher all
      cause mortality in both men and women, whereas a vegetable-based low-carbohydrate
      diet was associated with lower all-cause and cardiovascular disease mortality
      rates. PRIMARY FUNDING SOURCE: National Institutes of Health.

PMID- 20820039
TI  - The effect of financial incentives on hospitals that serve poor patients.
AB  - BACKGROUND: Providing financial incentives to hospitals to improve quality is
      increasingly common, yet its effect on hospitals that care for poor patients is
      largely unknown. OBJECTIVE: To determine how financial incentives for quality
      performance affect hospitals with more poor patients compared with those with
      fewer poor patients. DESIGN: Retrospective study. SETTING: U.S. hospitals.
      PARTICIPANTS: 251 hospitals that participated in the Premier Hospital Quality
      Incentive Demonstration program and a national sample of 3017 hospitals.
      MEASUREMENTS: The association between the disproportionate-share index, a marker
      of caring for poor patients, and baseline quality performance, changes in
      performance, and terminal performance for acute myocardial infarction, congestive
      heart failure, and pneumonia for hospitals in the pay-for-performance program and
      those in the national sample (which did not receive financial incentives).
      RESULTS: Among both pay-for-performance hospitals and those in the national
      sample, hospitals with more poor patients had lower baseline performance than did
      those with fewer poor patients. A high disproportionate-share index was
      associated with greater improvements in performance for acute myocardial
      infarction and pneumonia but not for congestive heart failure, and the gains were
      greater among hospitals that received financial incentives than among the
      national sample. After 3 years, hospitals that had more poor patients and
      received financial incentives caught up for all 3 conditions, whereas those with
      more poor patients among the national sample continued to lag. LIMITATION:
      Hospitals in the Premier Hospital Quality Incentive Demonstration may be
      atypical, and these results may not be generalizable to all hospitals.
      CONCLUSION: No evidence indicated that financial incentives widened the gap in
      performance between hospitals that serve poor patients and other hospitals. Pay
      for-performance programs may be a promising quality improvement strategy for
      hospitals that serve poor patients. PRIMARY FUNDING SOURCE: Robert Wood Johnson
      Foundation.

PMID- 20820040
TI  - Patients' and cardiologists' perceptions of the benefits of percutaneous coronary
      intervention for stable coronary disease.
AB  - BACKGROUND: It is unclear whether patients understand that percutaneous coronary
      intervention (PCI) reduces only chronic stable angina and not myocardial
      infarction (MI) or associated mortality. OBJECTIVE: To compare cardiologists' and
      patients' beliefs about PCI. DESIGN: Survey. SETTING: Academic center.
      PARTICIPANTS: 153 patients who consented to elective coronary catheterization and
      possible PCI, 10 interventional cardiologists, and 17 referring cardiologists.
      MEASUREMENTS: Patients' and cardiologists' beliefs about benefits of PCI. All
      cardiologists reported beliefs about PCI for patients in hypothetical scenarios.
      Interventional cardiologists also reported beliefs for study patients who
      underwent PCI. RESULTS: Of 153 patients, 68% had any angina, 42% had activity
      limiting angina, 77% had a positive stress test result, and 29% had had previous
      MI. The 53 patients who underwent PCI were more likely than those who did not to
      have a positive stress test result, but angina was similar in both groups. Almost
      three quarters of patients thought that without PCI, they would probably have MI
      within 5 years, and 88% believed that PCI would reduce risk for MI. Patients were
      more likely than physicians to believe that PCI would prevent MI (prevalence
      ratio, 4.25 [95% CI, 2.31 to 7.79]) or fatal MI (prevalence ratio, 4.83 [CI, 2.23
      to 10.46]). Patients were less likely than their physicians to report pre-PCI
      angina (prevalence ratio, 0.79 [CI, 0.67 to 0.92]). For the scenarios, 63% of
      cardiologists believed that the benefits of PCI were limited to symptom relief.
      Of cardiologists who identified no benefit of PCI in 2 scenarios, 43% indicated
      that they would still proceed with PCI in these cases. LIMITATION: The study was
      small and conducted at 1 center, and information about precatheterization
      counseling was limited. CONCLUSION: Cardiologists' beliefs about PCI reflect
      trial results, but patients' beliefs do not. Discussions with patients before PCI
      should better explain anticipated benefits. PRIMARY FUNDING SOURCE: None.

PMID- 20820041
TI  - Meta-analysis: Accuracy of contrast-enhanced magnetic resonance angiography for
      assessing steno-occlusions in peripheral arterial disease.
AB  - BACKGROUND: Contrast-enhanced magnetic resonance angiography (MRA) is a
      noninvasive, radiation-free imaging method for studying peripheral arterial
      disease (PAD) of the lower extremities. PURPOSE: To summarize evidence of
      prospective studies about how well MRA identifies or excludes arterial steno
      occlusions (50% to 100% lumen reduction) in adults with PAD symptoms. DATA
      SOURCES: PubMed and 3 other databases were searched from 1998 to 2009 without
      language restrictions. STUDY SELECTION: Two independent reviewers selected 32
      studies that compared MRA with intra-arterial digital subtraction angiography in
      PAD. Eligible studies were prospective and provided data to reconstruct 2 x 2 or
      3 x 3 contingency tables (<50% stenosis vs. > or =50% stenosis or occlusion of
      arterial segments) in at least 10 patients with PAD symptoms. DATA EXTRACTION:
      Two reviewers independently assessed the study quality and extracted the study
      data, with disagreements resolved by consensus. DATA SYNTHESIS: The 32 included
      studies generally had high methodological quality. About 26% of the 1022 included
      patients had critical limb ischemia with pain at rest or tissue loss. Overall,
      the pooled sensitivity of MRA was 94.7% (95% CI, 92.1% to 96.4%) and the
      specificity was 95.6% (CI, 94.0% to 96.8%) for diagnosing segmental steno
      occlusions. The pooled positive and negative likelihood ratios were 21.56 (CI,
      15.70 to 29.69) and 0.056 (CI, 0.037 to 0.083), respectively. Magnetic resonance
      angiography correctly classified 95.3%, overstaged 3.1%, and understaged 1.6% of
      arterial segments. LIMITATION: Similar to most studies of computed tomographic
      angiography in PAD, the primary studies reported the diagnostic accuracy of MRA
      on a per-segment basis, not a per-patient basis. CONCLUSION: This meta-analysis
      of 32 prospective studies further increases the evidence that contrast-enhanced
      MRA has high accuracy for identifying or excluding clinically relevant arterial
      steno-occlusions in adults with PAD symptoms. PRIMARY FUNDING SOURCE: None.

PMID- 20820042
TI  - Hepatic encephalopathy in our genes?

PMID- 20820043
TI  - Animal, vegetable, or ... clinical trial?

PMID- 20820044
TI  - Does pay-for-performance steal from the poor and give to the rich?

PMID- 20820045
TI  - Improving the quality of informed consent: it is not all about the risks.

PMID- 20820046
TI  - Charlie's List.

PMID- 20820047
TI  - Misleading interpretations and public misinformation on human growth hormone in
      athletes.

PMID- 20820048
TI  - Misleading interpretations and public misinformation on human growth hormone in
      athletes.

PMID- 20820050
TI  - Limitations of the MEDLINE database in constructing meta-analyses.

PMID- 20820051
TI  - Vessels of mercy.

PMID- 20820054
TI  - Long work hours and physical fitness: 30-year risk of ischaemic heart disease and
      all-cause mortality among middle-aged Caucasian men.
AB  - BACKGROUND: No previous long-term studies have examined if workers with low
      physical fitness have an increased risk of cardiovascular mortality due to long
      work hours. The aim of this study was to test this hypothesis. METHODS: The study
      comprised 30-year follow-up of a cohort of 5249 gainfully employed men aged 40
      59years in the Copenhagen Male Study. 274 men with cardiovascular disease were
      excluded from the follow-up. Physical fitness (maximal oxygen consumption,
      Vo(2)max) was estimated using the Astrand bicycle ergometer test, and number of
      work hours was obtained from questionnaire items; 4943 men were eligible for the
      incidence study. RESULTS: 587 men (11.9%) died because of ischaemic heart disease
      (IHD). Cox analyses adjusted for age, blood pressure, smoking, alcohol, body mass
      index, diabetes, hypertension, physical work demands, and social class, showed
      that working more than 45h/week was associated with an increased risk of IHD
      mortality in the least fit (Vo(2)max range 15-26; HR 2.28, 95% CI 1.10 to 4.73),
      but not intermediate (Vo(2)max range 27-38; HR 0.94, 95% CI 0.59 to 1.51) and
      most fit men (Vo(2)max range 39-78; HR 0.91, 95% CI 0.41 to 2.02) referencing men
      working less than 40h/week. CONCLUSIONS: The findings indicate that men with low
      physical fitness are at increased risk for IHD mortality from working long hours.
      Men working long hours should be physically fit.

PMID- 20820056
TI  - We are getting there!

PMID- 20820055
TI  - The association between quality of primary care, deprivation and cardiovascular
      outcomes: a cross-sectional study using data from the UK Quality and Outcomes
      Framework.
AB  - BACKGROUND: The Quality and Outcomes Framework, a financial incentive scheme for
      general practitioners in the UK, seems to have improved the quality of primary
      care and reduced inequalities in primary care delivery. It remains unclear,
      however, whether higher-quality primary care improves health outcomes or reduces
      health inequalities. METHODS: We conducted a cross-sectional study examining the
      association between quality of cardiovascular care and coronary heart disease
      (CHD) outcomes in 1531 general practices in London. We calculated CHD quality
      achievement scores (ranging from 0 to 100) for each practice using the 2006-2007
      data from the Quality and Outcomes Framework. We used weighted linear regression
      models to assess the practice-level association between the CHD quality score and
      CHD admissions and deaths. FINDINGS: Overall, practices with higher CHD quality
      achievement scores had better CHD outcomes. Each one point increase in the CHD
      quality achievement score was associated with 4.28 (95% CI 1.19 to 7.38; p=0.007)
      fewer admissions per 100,000 for practices serving highly deprived populations
      and 2.11 (95% CI 0.68 to 3.55; p=0.004) fewer admissions per 100 000 for
      practices serving populations of average deprivation. There was no association
      between the CHD quality achievement score and the CHD admissions for practices
      serving affluent populations (p=0.906). We observed a similar deprivation
      dependent gradient between quality achievement and CHD deaths. INTERPRETATION:
      High-quality primary care is associated with improved health outcomes. This
      association is strongest in deprived areas, suggesting that high-quality primary
      care may play an important role in reducing health inequalities.

PMID- 20820057
TI  - Sports injuries and illnesses during the Winter Olympic Games 2010.
AB  - BACKGROUND: Identification of high-risk sports, including their most common and
      severe injuries and illnesses, will facilitate the identification of sports and
      athletes at risk at an early stage. AIM: To analyse the frequencies and
      characteristics of injuries and illnesses during the XXI Winter Olympic Games in
      Vancouver 2010. METHODS: All National Olympic Committees' (NOC) head physicians
      were asked to report daily the occurrence (or non-occurrence) of newly sustained
      injuries and illnesses on a standardised reporting form. In addition, the medical
      centres at the Vancouver and Whistler Olympic clinics reported daily on all
      athletes treated for injuries and illnesses. RESULTS: Physicians covering 2567
      athletes (1045 females, 1522 males) from 82 NOCs participated in the study. The
      reported 287 injuries and 185 illnesses resulted in an incidence of 111.8
      injuries and 72.1 illnesses per 1000 registered athletes. In relation to the
      number of registered athletes, the risk of sustaining an injury was highest for
      bobsleigh, ice hockey, short track, alpine freestyle and snowboard cross (15-35%
      of registered athletes were affected in each sport). The injury risk was lowest
      for the Nordic skiing events (biathlon, cross country skiing, ski jumping, Nordic
      combined), luge, curling, speed skating and freestyle moguls (less than 5% of
      registered athletes). Head/cervical spine and knee were the most common injury
      locations. Injuries were evenly distributed between training (54.0%) and
      competition (46.0%; p=0.18), and 22.6% of the injuries resulted in an absence
      from training or competition. In skeleton, figure and speed skating, curling,
      snowboard cross and biathlon, every 10th athlete suffered from at least one
      illness. In 113 illnesses (62.8%), the respiratory system was affected.
      CONCLUSION: At least 11% of the athletes incurred an injury during the games, and
      7% of the athletes an illness. The incidence of injuries and illnesses varied
      substantially between sports. Analyses of injury mechanisms in high-risk Olympic
      winter sports are essential to better direct injury-prevention strategies.

PMID- 20820058
TI  - Risk of injury on third-generation artificial turf in Norwegian professional
      football.
AB  - BACKGROUND: Artificial turf is used extensively in both recreational and elite
      football in areas with difficult climatic conditions. OBJECTIVE: To compare the
      risk for acute injuries between natural grass (NG) and third-generation
      artificial turf (3GAT) in male professional football. study design: Prospective
      cohort study. METHODS: All injuries sustained by players with a first-team
      contract were recorded by the medical staff of each club, from the 2004
      throughout the 2007 season. An injury was registered if the player was unable to
      take fully part in football activity or match play. RESULTS: A total of 668 match
      injuries, 526 on grass and 142 on artificial turf, were recorded. The overall
      acute match injury incidence was 17.1 (95% CI 15.8 to 18.4) per 1000 match hours;
      17.0 (95% CI 15.6 to 18.5) on grass and 17.6 (95% CI 14.7 to 20.5) on artificial
      turf. Correspondingly, the incidence for training injuries was 1.8 (95% CI 1.6 to
      2.0); 1.8 (95% CI 1.5 to 2.0) on grass and 1.9 (95% CI 1.5 to 2.2) on artificial
      turf respectively. No significant difference was observed in injury location,
      type or severity between turf types. CONCLUSION: No significant differences were
      detected in injury rate or pattern between 3GAT and NG in Norwegian male
      professional football.

PMID- 20820059
TI  - Injuries among World Cup freestyle skiers.
AB  - BACKGROUND: Limited knowledge exists on injuries among professional freestyle
      skiers. OBJECTIVE: To describe the risk of injury and injury patterns among
      competitive World Cup (WC) freestyle skiers during the competitive season.
      METHODS: Retrospective interviews were conducted with WC freestyle skiers from 20
      nations in a cohort study at the end of the 2006-2007, 2007-2008 and 2008-2009
      winter seasons, and all acute injuries occurring during the 4.5 month competitive
      season were recorded. If an athlete was not present, we interviewed his or her
      coach or medical personnel. RESULTS: A total of 291 acute injuries were recorded
      among 662 WC freestyle skiers. Ninety-three injuries (32%) were severe in nature,
      defined as >28 days absence from training/competition. This corresponds to 14
      (95% CI 11.2 to 16.9) injuries per 100 athletes per season. The most frequently
      injured body part was the knee with 77 injuries (27%) and 37 of these were
      severe. The head was the next most commonly injured body part with 39 (13%)
      injuries. As many as 106 injuries (36%) occurred during WC/World Ski Championship
      competitions, corresponding to an injury rate of 15.6 injuries per 1000 runs (95%
      CI 12.7 to 18.6). There were no significant differences between men and women in
      either the injury rate or the rate seen for knee injuries. CONCLUSIONS: The
      injury rate among WC athletes in freestyle skiing is high, especially for severe
      injuries. The knee is the most commonly injured body part, also dominated by
      severe injuries. We found no significant difference in the injury rate related to
      sex.

PMID- 20820060
TI  - Are there risk factors for snowboard injuries? A case-control multicentre study
      of 559 snowboarders.
AB  - OBJECTIVE: To analyse risk factors leading to injuries during snowboarding.
      DESIGN: A case-control multicentre survey of injured and non-injured
      snowboarders. SETTING: One tertiary and two secondary trauma centres in Bern,
      Switzerland. METHODS: All snowboard injuries admitted to our tertiary and two
      affiliated secondary trauma centres from 1 November 2007 to 15 April 2008 were
      analysed on the basis of a completed questionnaire incorporating 15 variables.
      The same questionnaire was applied in non-injured controls at valley stations
      after a snowboarding day during the same period. A multiple logistic regression
      was performed (dichotomous variables). Patterns of combined risk factors were
      calculated by inference trees. RESULTS: 306 patients and 253 controls were
      interviewed. The following variables were statistically significant for the
      injured PATIENTS: low readiness for speed (OR 0.20, 95% CI 0.06 to 0.64,
      p=0.0037), bad weather/visibility (OR 19.06, 95% CI 2.70 to 134.73, p=0.0031) and
      old snow (OR 0.11, 95% CI 0.02 to 0.68, p=0.0323). Not wearing a helmet and
      riding on icy slopes emerged as a combination of risk factors associated with
      injury. CONCLUSIONS: Several risk factors and combinations exist, and different
      risk profiles were identified. Future research should be aimed at more precise
      identification of groups at risk and developing specific recommendations for each
      group-for example, a snow-weather conditions index at valley stations.

PMID- 20820061
TI  - HIV prevalence and risk behaviours among men having sex with men in Nigeria.
AB  - OBJECTIVE: To evaluate HIV and syphilis prevalence among men who have sex with
      men (MSM) in Nigeria, and assess their HIV-related risk behaviours and exposure
      to HIV prevention interventions. METHODS: Cross-sectional study using respondent
      driven sampling conducted in Lagos, Kano and Cross River states, Nigeria, between
      July and September 2007. RESULTS: A total of 879 MSM participated, 293 from each
      state. Eight participants (1.1%, CI 0.1% to 2.2%) in Cross River, 27 (9.3%, CI
      5.7% to 15.4%) in Kano and 74 (17.4%, CI 12.3% to 23.2%) in Lagos tested positive
      for HIV. No syphilis was detected. The median age was 22 years. MSM reported an
      average of 4.2 male anal sex partners in the past 6 months. Between 24.4% (Lagos)
      and 36.0% (Kano) of MSM reported selling sex to other men. Up to 49.7% of MSM
      reported sex with a girlfriend and <= 6.5% purchased sex from female sex workers.
      Consistent condom use in commercial sex with other men over the past 6 months
      ranged from 28.0% (Cross River) to 34.3% (Kano), in contrast to between 23.9%
      (Kano) and 45.8% (Lagos) for non-commercial sex. Associations with HIV positivity
      included age in the three states, having been the receptive partner in anal sex
      in the past 6 months in Lagos and in Lagos and Kano feeling at risk of HIV.
      CONCLUSION: Large differentials in HIV prevalence between states together with
      high mobility, inconsistent condom use and behavioural links with female sex
      partners, have the potential for further HIV transmission within MSM networks,
      and between MSM and the general population.

PMID- 20820062
TI  - Images in thorax. The atoll sign.

PMID- 20820063
TI  - Tracheo-bronchial involvement in Sweet syndrome.

PMID- 20820064
TI  - Factors that predict failure in home management of an acute exacerbation of COPD.

PMID- 20820065
TI  - Clinical outcomes of pandemic (H1N1) 2009 influenza (swine flu) in adults with
      cystic fibrosis.

PMID- 20820066
TI  - [Ritalin for better or worse[Editorial]].

PMID- 20820067
TI  - [Clostridium difficile infections. An increasing problem in westernized
      medicine[Editorial]].

PMID- 20820068
TI  - [Clostridium difficile infections at Landspitali - 1998-2008].
AB  - OBJECTIVE: To study the epidemiology and severity of C. difficile infections
      (CDI) at Landspitali over 11 year period, 1998-2008. MATERIAL AND METHODS: CDI
      were identified by a positive toxin assay in stools from the database of the
      Department of Microbiology. Chart review was conducted on patients diagnosed in
      January and June each year during the study period, a total of 237 infections.
      RESULTS: Overall, 1,861 of 11,968 submitted stool samples were positive for C.
      difficile toxin, representing 1,492 infections. The population-based incidence
      was 29% higher in the end than in the beginning of the period and was highest in
      the age group >80 years where it was 387 cases per 100,000 person-years. The
      incidence per 1,000 admissions and 10,000 hospital days increased by 71% and
      102%, respectively. 47% of the infections were nosocomial. Most patients had
      history of antibiotic exposure prior to the infection and the most common symptom
      was diarrhea. Response to a single antibiotics course was good (93%). No patient
      required surgery due to colitis. CONCLUSION: The incidence of CDI was higher in
      2008 than 11 years before. Most patients had well characterized risk factors for
      CDI. For most patients a single course of metronidazole treatment resolved the
      infection. Based on these data, the severity of CDI does not seem to be
      increasing in Iceland.

PMID- 20820069
TI  - [An evaluation of diagnosis and treatment of acute sinusitis at three health care
      centers].
AB  - OBJECTIVE: The objective of this study was to evaluate the diagnosis and
      treatment of acute sinusitis at three health care centers in northern and eastern
      Iceland. MATERIAL AND METHODS: Information on all those diagnosed with acute
      sinusitis (ICD 10 J01.0, J01.9) in the year 2004 at the communal health care
      centers in Akureyri, Husavik and Egilsstadir was obtained retrospectively from
      computerized clinical records. Key factors used for diagnosis and treatment were
      recorded. In order to obtain an equal distribution in population size only about
      one-third of the diagnoses made in Akureyri were included in the search (the
      first ten days of every month). RESULTS: The search yielded a total of 468
      individuals. The average incidence of acute sinusitis was found to be 3.4 per 100
      inhabitants per year. Adherence to clinical guidelines (albeit from other
      countries) regarding diagnosis of bacterial sinusitis was nearly nonexistent.
      There were considerable differences found between health care centers as to
      whether x-rays were used for diagnostic purposes. Blood tests were hardly used at
      all. The disease was diagnosed over the telephone in 28% of the cases (Husavik
      38%, Akureyri 32%, Egilsstadir 10%). Over 90% of all individuals diagnosed with
      acute sinusitis received antibiotics, regardless of symptom duration. The
      antibiotics most often prescribed were Doxycyclin and Amoxicillin. CONCLUSIONS:
      The incidence of acute sinusitis in these three communities seems to be similar
      to other western countries. Acute bacterial sinusitis seems to be overdiagnosed
      and the use of antibiotics is in no context with clinical guidelines. Our results
      support the hypothesis that physicians tend to regard acute sinusitis as a
      bacterial disease, and treat it accordingly.

PMID- 20820070
TI  - [Cost- effectiveness analysis of pneumococcal vaccination in Iceland].
AB  - OBJECTIVE: Pneumococcus is a common cause of disease among children and the
      elderly. With the emergence of resistant serotypes, antibiotic treatment is
      getting limited. Many countries have therefore introduced a vaccination program
      among children against the most common serotypes. The aim of this study was to
      analyse cost-effectiveness of adding a vaccination program against pneumococcus
      in Iceland. MATERIAL AND METHODS: A cost-effectiveness analysis was carried out
      from a societal perspective where the cost-effectiveness ratio ICER was estimated
      from the cost of each additional life and life year saved. The analyse was based
      on the year 2008 and all cost were calculated accordingly. The rate of 3% was
      used for net present-value calculation. RESULTS: Annual societal cost due to
      pneumococcus in Iceland was estimated to be 718.146.252 ISK if children would be
      vaccinated but 565.026.552 ISK if they would not be vaccinated. The additional
      cost due to the vaccination program was therefore 153.119.700 ISK . The
      vaccination program could save 0,669 lives among children aged 0-4 years old and
      21.11 life years. The cost was 228.878.476 ISK for each additional life saved and
      7.253.420 ISK for each additional life year saved. CONCLUSION: Given initial
      assumptions the results indicate that a vaccination programme against
      pneumococcal disease in Iceland would be cost effective.

PMID- 20820071
TI  - [Case of the month: Leydig cell testicular tumor].

PMID- 20820072
TI  - Kernel optimization in discriminant analysis.
AB  - Kernel mapping is one of the most used approaches to intrinsically derive
      nonlinear classifiers. The idea is to use a kernel function which maps the
      original nonlinearly separable problem to a space of intrinsically larger
      dimensionality where the classes are linearly separable. A major problem in the
      design of kernel methods is to find the kernel parameters that make the problem
      linear in the mapped representation. This paper derives the first criterion that
      specifically aims to find a kernel representation where the Bayes classifier
      becomes linear. We illustrate how this result can be successfully applied in
      several kernel discriminant analysis algorithms. Experimental results, using a
      large number of databases and classifiers, demonstrate the utility of the
      proposed approach. The paper also shows (theoretically and experimentally) that a
      kernel version of Subclass Discriminant Analysis yields the highest recognition
      rates.

PMID- 20820074
TI  - Reliability Fusion of Time-of-Flight Depth and Stereo Geometry for High Quality
      Depth Maps.
AB  - Time-of-flight range sensors have error characteristics, which are complementary
      to passive stereo. They provide real-time depth estimates in conditions where
      passive stereo does not work well, such as on white walls. In contrast, these
      sensors are noisy and often perform poorly on the textured scenes where stereo
      excels. We explore their complementary characteristics and introduce a method for
      combining the results from both methods that achieve better accuracy than either
      alone. In our fusion framework, the depth probability distribution functions from
      each of these sensor modalities are formulated and optimized. Robust and adaptive
      fusion is built on a pixel-wise reliability weighting function calculated for
      each method. In addition, since time-of-flight devices have primarily been used
      as individual sensors, they are typically poorly calibrated. We introduce a
      method that substantially improves upon the manufacturer's calibration. We
      demonstrate that our proposed techniques lead to improved accuracy and robustness
      on an extensive set of experimental results. 

PMID- 20820075
TI  - Single Image Haze Removal Using Dark Channel Prior.
AB  - In this paper, we propose a simple but effective image prior-dark channel prior
      to remove haze from a single input image. The dark channel prior is a kind of
      statistics of outdoor haze-free images. It is based on a key observation-most
      local patches in outdoor haze-free images contain some pixels whose intensity is
      very low in at least one color channel. Using this prior with the haze imaging
      model, we can directly estimate the thickness of the haze and recover a high
      quality haze-free image. Results on a variety of hazy images demonstrate the
      power of the proposed prior. Moreover, a high-quality depth map can also be
      obtained as a byproduct of haze removal. 

PMID- 20820076
TI  - Multiview stereo and silhouette consistency via convex functionals over convex
      domains.
AB  - We propose a convex formulation for silhouette and stereo fusion in 3D
      reconstruction from multiple images. The key idea is to show that the
      reconstruction problem can be cast as one of minimizing a convex functional,
      where the exact silhouette consistency is imposed as convex constraints that
      restrict the domain of feasible functions. As a consequence, we can retain the
      original stereo-weighted surface area as a cost functional without heuristic
      modifications of this energy by balloon terms or other strategies, yet still
      obtain meaningful (non-empty) reconstructions which are guaranteed to be
      silhouette-consistent. We prove that the proposed convex relaxation approach
      provides solutions that lie within a bound of the optimal solution. Compared to
      existing alternatives, the proposed method does not depend on initialization and
      leads to a simpler and more robust numerical scheme for imposing silhouette
      consistency obtained by projection onto convex sets. We show that this projection
      can be solved exactly using an efficient algorithm. We propose a parallel
      implementation of the resulting convex optimization problem on a graphics card.
      Given a photo-consistency map and a set of image silhouettes, we are able to
      compute highly accurate and silhouette-consistent reconstructions for challenging
      real-world data sets. In particular, experimental results demonstrate that the
      proposed silhouette constraints help to preserve fine-scale details of the
      reconstructed shape. Computation times depend on the resolution of the input
      imagery and vary between a few seconds and a couple of minutes for all
      experiments in this paper.

PMID- 20820077
TI  - Approximately global optimization for robust alignment of generalized shapes.
AB  - In this paper, we introduce a novel method to solve shape alignment problems. We
      use gray-scale "images" to represent source shapes, and propose a novel two
      component Gaussian Mixture (GM) distance map representation for target shapes.
      This asymmetric representation is a flexible image-based representation which is
      able to represent different kinds of shape data, including continuous contours,
      unstructured sparse point sets, edge maps, and even gray-scale gradient maps.
      Using this representation, a new energy function based on a novel two-component
      Gaussian Mixture distance model is proposed. The new energy function was
      empirically evaluated to be a more robust shape dissimilarity metric that can be
      computed efficiently. Such high efficiency is essential for global optimization
      methods. We adopt and modify one of them, the Particle Swarm Optimization (PSO),
      to effectively estimate the global optimum of the new energy function.
      Differently from the original PSO, several new strategies were employed to make
      the optimization more robust and prevent it from converging prematurely. The
      overall performance of the proposed framework as well as the properties of each
      algorithmic component were evaluated and compared with those of some state-of-the
      art methods. Extensive experiments and comparison performed on generalized 2D and
      3D shape data demonstrate the robustness and effectiveness of the method.

PMID- 20820078
TI  - Direct method for video-based navigation using a digital terrain map.
AB  - A novel vision-based navigation algorithm is proposed. The gray levels of two
      images, together with a Digital Terrain Map (DTM), are directly utilized to
      define constraints on the navigation parameters. The feasibility of the algorithm
      is examined both under a simulated environment and using real flight data.

PMID- 20820079
TI  - Novel nonlinear knowledge-based mean force potentials based on machine learning.
AB  - The prediction of 3D structures of proteins from amino acid sequences is one of
      the most challenging problems in molecular biology. An essential task for solving
      this problem with coarse-grained models is to deduce effective interaction
      potentials. The development and evaluation of new energy functions is critical to
      accurately modeling the properties of biological macromolecules. Knowledge-based
      mean force potentials are derived from statistical analysis of proteins of known
      structures. Current knowledge-based potentials are almost in the form of weighted
      linear sum of interaction pairs. In this study, a class of novel nonlinear
      knowledge-based mean force potentials is presented. The potential parameters are
      obtained by nonlinear classifiers, instead of relative frequencies of interaction
      pairs against a reference state or linear classifiers. The support vector machine
      is used to derive the potential parameters on data sets that contain both native
      structures and decoy structures. Five knowledge-based mean force Boltzmann-based
      or linear potentials are introduced and their corresponding nonlinear potentials
      are implemented. They are the DIH potential (single-body residue-level Boltzmann
      based potential), the DFIRE-SCM potential (two-body residue-level Boltzmann-based
      potential), the FS potential (two-body atom-level Boltzmann-based potential), the
      HR potential (two-body residue-level linear potential), and the T32S3 potential
      (two-body atom-level linear potential). Experiments are performed on well
      established decoy sets, including the LKF data set, the CASP7 data set, and the
      Decoys "R"Us data set. The evaluation metrics include the energy Z score and the
      ability of each potential to discriminate native structures from a set of decoy
      structures. Experimental results show that all nonlinear potentials significantly
      outperform the corresponding Boltzmann-based or linear potentials, and the
      proposed discriminative framework is effective in developing knowledge-based mean
      force potentials. The nonlinear potentials can be widely used for ab initio
      protein structure prediction, model quality assessment, protein docking, and
      other challenging problems in computational biology.

PMID- 20820080
TI  - Role and current situation of TURP in patients with elevated PSA.
AB  - OBJECTIVES: The aim of this review is to evaluate the place of transurethral
      resection of the prostate (TURP) in patients with elevated and/or rising prostate
      specific antigen (PSA). The role of TURP in these patients is assessed in
      symptomatic as well as in asymptomatic patients. METHODS: Current literature
      (1987-2009) was reviewed with regard to this specific population. This research
      was performed using the Medline online search tools. RESULTS: Initially, possible
      therapeutic strategies other than TURP could be used in patients with elevated
      and/or rising PSA values and no sign of proven prostate cancer. Consequently, the
      value of TURP in patients with elevated and/or rising PSA and no proven prostate
      cancer is discussed. In this setting, TURP can be executed with or without
      concomitant prostate biopsies. Furthermore, TURP can be proposed to patients with
      and without lower urinary tract symptoms. CONCLUSIONS: In this review, we
      evaluated the role of TURP in patients with elevated and/or rising PSA values and
      no proven prostate cancer. We believe TURP has a place in this particular
      population even in patients without lower urinary tract symptoms. This strategy
      is well founded on solid ground after an extensive review of the available
      literature. In most cases, a TURP will result in a normalization of PSA as well
      as a symptomatic benefit. Additionally, this procedure will allow histological
      evaluation which might show a possible life threatening prostate cancer in some
      patients.

PMID- 20820081
TI  - Effect of american cranberry (Cysticlean) on Escherichia coli adherence to
      bladder epithelial cells. In vitro and in vivo study.
AB  - OBJECTIVES: The American cranberry proanthocyanidins (PACs) are the main
      responsible for its efficacy in urinary tract infections. Their mechanism of
      action is related to inhibition of Escherichia coli to urothelial cells.
      Cysticlean contains an extract of American cranberry which provides 118 mg of
      PACs per dose. The activity of Cysticlean tablets on Escherichia Coli adherence
      to bladder epithelial cells has been studied in vitro. Moreover, the activity of
      Cistyclean both in powder for oral suspension and tablets has been compared ex
      vivo. METHODS: The rats received both Cysticlean preparations per orem, and urine
      from each animal was collected during the following 16 hours and preincubated
      with E. coli. Subsequently, bacteria were incubated with T24 cells. After 1 hour
      the number of bacteria adhered per cell was calculated. For the in vitro study,
      E. Coli preincubated at various concentrations of the products were incubated
      with T24 cells and the same process previously referred was carried out. RESULTS:
      Urine samples from rats taking Cysticlean powder for oral suspension and tablets
      (118 mg PACs/animal) showed an important inhibition of E. Coli adherence (83% and
      52%respectively). The inferior dose of 59 mg PACs/animal also showed marked
      inhibition of E. Coli adherence (29% after Cysticlean tablets intake and 40% for
      powder). In vitro, Cysticlean showed inhibition of bacterial adherence in all
      tested concentrations: 5, 25 and 75 PACs mg/ml, diminishing the number og
      bacteria adhered to epithelial cells by 25%, 36% and 34% respectively.
      CONCLUSIONS: Cysticlean shows a significant inhibition of E. Coli adherence to
      urothelial cells. Cysticlean powder for suspension preparation is more effective
      tha tablets. Cysticlean powder for suspension is well tolerated, and compliance
      has been observed. Its use is very recommendable in pediatric urinary tract
      infection prophylaxis. Due to the variety of products with American cranberry
      extracts in the market, with different proanthocyanidins declared content, it
      would be interesting to compare their activity using established pharmacological
      methods.

PMID- 20820082
TI  - Our experience in the treatment of male stress urinary incontinence with the male
      Remeex system.
AB  - OBJECTIVES: We show our experience in the treatment of post-prostatectomy stress
      urinary incontinence with the male Remeex system (MRS). We also describe the
      elements of the system, its therapeutic indications, technical implantation and
      appropriate adjustment. METHODS: From March 2007 to January 2009 five male
      patients aged 57 to 71 years (mean age 66 years) with postprostatectomy stress
      urinary incontinence were operated on to insert a suburethral readjustable sling
      (Remeex). All patients had severe urinary incontinence with deterioration of
      their quality of life. The evolution period ranged from 2 to 10 years with an
      average of 3.5 years, requiring from 5 to 8 pads a day. RESULTS: All patients are
      continent after a mean follow up of 15.4 months (range 6-28 months). Only two of
      them use one security pad when they perform physical efforts. The Incontinence
      Impact Questionnaire (7) scores before surgery and 6 months after diminished from
      68+/-7 to 10+/-3. All patients are very satisfied. CONCLUSIONS: MRS is a valid
      therapeutic option for post-prostatectomy incontinence, being a reproducible
      technique, of easy execution, that allows readjustment through a suprapubic
      incision under local anesthesia as an outpatient procedure. It has a low
      complication rate with excellent and endured results.

PMID- 20820083
TI  - [Correlation of bladder thickness on ultrasound with clinical and urodynamic data
      in symptomatic benign prostatic hyperplasia].
AB  - OBJECTIVES: Our objective is to verify the diagnostic usefulness of ultrasound
      measurement of the thickness of the bladder wall, and the correlation with
      clinical/ urodynamic findings in patients with symptomatic BPH. METHODS: We
      performed a prospective cross-sectional study (cross-sectional study '') in a
      series of 74 males (age chi= 72.4 S = 7.1 (56-84 years) with symptomatic BPH.
      Patients completed the IPSS and determined the plasma level of PSAt (ng / ml).
      Before performing the urodynamic study, was determined by transabdominal
      ultrasonography (3.5 MHz transducer): prostate volume (cc) by the ellipsoid
      formula, and bladder wall thickness (mm) measured on the anterior bladder wall.
      Statistical analysis was performed using ANOVA, the Pearson correlation, and ROC
      curve. RESULTS: It was a significant correlation of the sonographic thickness of
      the bladder wall with the IPSS (p = 0001, r = 0.38) (parameter in turn highly
      correlated with prostate volume and PSA (p = 0.01, r = 0.62)), as well as the
      detrusor hyperactivity (p = 0.03, r =0.21), cut off ROC curve: 3.85 mm. Instead,
      it was not shown a significant correlation between the sonographic thickness of
      the bladder wall and the urodynamic diagnosis of obstruction (Abrams and number
      Griffths p = 0223, r = 0.14) or the detrusor contractile power, measured in power
      at peak flow (Pw) (p = 0642 r =- 0.55), nor with age (p = 0303, r = 0.12).
      Neither correlation was observed with other non-invasive urodynamic measures (the
      maximum urinary flow flowmetry (p = 0318, r = 0.12) and percentage
      postmicturition residual (p = 0696, r = 0.05)). CONCLUSIONS: The ultrasound
      measurement of bladder wall thickness, although it has not proved useful ness in
      our series in the diagnosis of the voiding phase (lower urinary tract obstruction
      and detrusor contractility impairment), on the contrary it can be introduced as a
      diagnostic technique for non-invasive studies in the alterations of the filling
      phase, in the form of detrusor hyperactivity in also patients with symptomatic
      BPH, and present a significant correlation with prostate growth.

PMID- 20820084
TI  - Is urinary tract infection after shock wave lithotripsy an aggravating factor for
      renal damage?
AB  - OBJECTIVES: To prospectively assess if urinary tract infection (UTI) after
      extracorporeal shock wave lithotripsy (ESWL) enhances immediate renal damage in
      patients with renal stones. METHODS: Levels of lactic dehydrogenase (LDH),
      creatine phosphokinase (CPK), and beta2 microglobulin were measured in the urine
      of 171 patients, before and after ESWL for treatment of up to 3 cm renal stones.
      Standard investigation included urine sample before and after treatment. Patients
      were divided in two groups in accordance to presence of positive bacterial urine
      sample after ESWL. Changes in biomarker values pre and post- ESWL were assessed
      via X2 test for both groups and compared between the two groups for post
      treatment values. RESULTS: Despite pre-treatment antibiotic therapy, 21.6% of the
      patients presented with UTI after ESWL. In the group with clear post-treatment
      urine samples there was a 5.8, 2.2, and 0.7 fold increase of CPK, LDH, and beta2
      microglobulin levels after ESWL, respectively (p<0.001), indicating some degree
      of immediate renal damage. In patients with UTI, the levels of the enzymes
      elevated by 80, 15, and 2.2 fold after ESWL, respectively, which represents a
      significantly increased elevation comparing with the sterile urine group
      (p<0.001). CONCLUSIONS: ESWL results in transient immediate renal damage, which
      is exaggerated in patients with persistent or treatment prompted UTI. Long-term
      importance of this finding must be determined.

PMID- 20820085
TI  - Enterocutaneous fistula as a complication of percutaneous nephrolithotomy in
      patients with previous bariatric surgery: case report and bibliographic review.
AB  - OBJECTIVE: Enterocutaneous fistula is a rare complication after percutaneous
      nephrolithotomy. Some situations are risk factors for it to occur, such as
      horseshoe kidney, retrorenal colon and chronic colonic dilation by several
      factors, among them late postoperative time after yeyunoileal bypass in morbid
      obesity treatment. METHODS: 35-year-old female patient with a 2.5 cm calculus in
      the right renal pelvis. Late postoperative time after bariatric surgery using
      duodenal switch technique, and 55 kg lost till present. She undergone
      percutaneous nephrolithotomy (PCNL) with two punctures, one in the lower calyx,
      lost during dilation, and other in the upper calyx through which surgery was
      successfully carried out. During immediate postoperative time it enteric
      secretions were observed through the lower chalice puncture. Once the
      intraperitoneal lesion was removed, decision for conservative treatment was taken
      with fistula drainage, broadspectrum antibiotic therapy, fasting and total
      parenteral nutrition. The fistula debt ceased in the 8th postoperative (PO) day,
      when drain and nephrostomy tube were withdrawn and patient was discharged from
      the hospital on 10th PO day. On ambulatory follow up the patient is in good
      conditions. RESULTS: One case of enterocutaneous fistula after PNL presented in a
      patient in late postoperative time after yeyunoileal bypass. She was successfully
      treated by conservative therapy. Several authors point to chronic colonic
      distention and to great loss of retroperitoneal fat as causes for the increase of
      inadvertent colonic punctures in percutaneous renal access. CONCLUSIONS: The risk
      of complications with enterocutaneous fistula is significantly higher during the
      postoperatory in patients of bariatric surgery than in others.

PMID- 20820086
TI  - Early age renal synovial sarcoma.
AB  - OBJECTIVE: We report a primary renal Synovial Sarcoma (SS) case and analyze its
      features. METHOD: A 15 year old male presented with left abdominal mass and
      weight loss. CT scan images showed a 13 cm mass located in the lower pole of the
      left kidney. Renal biopsy recognized an undifferentiated neoplasm, the
      immunohistochemistry suggesting the probability of neuroectodermic primitive
      tumor versus SS. Chemotherapy and radical nephrectomy were carried out.
      Pathological study showed a big multilobulated necrotic tumor 22 x 13 x 12.5 cm.
      Histopathological study demonstrated a neoplasm composed by immature cells.
      Currently, patient has survived 1,8 years. A structured bibliographical search
      was performed in the Medline, Imbiomed and Scielo databases. RESULTS: The final
      immunohistochemistry studies gave the diagnosis of poorly differentiated renal SS
      small cell variety. CONCLUSION: The renal SS is extremely infrequent, with less
      than 40 cases reported, of which this case reports the earlier age. These tumors,
      when located in the kidney, represent a great diagnostic challenge that requires
      adequate clinical, radiological, surgical, and pathological correlation for
      appropriate diagnosis and treatment.

PMID- 20820087
TI  - Tumor inside an inguinoscrotal bladder hernia.
AB  - OBJECTIVE: To describe two cases of urothelial tumors in inguinoscrotal bladder
      hernias and comment on the low incidence of this condition. METHODS: Two patients
      were diagnosed and treated by partial cystectomy and hernia repair. RESULTS: The
      clinical outcome of both patients was good at two and three years, respectively,
      and neither patient experienced hernia or tumor recurrence. CONCLUSIONS: Inguinal
      bladder hernias are relatively common. However, few reports of tumor in the
      herniated bladder have been published. Treatment consists of tumor removal,
      hernia repair and treatment of any associated urethroprostatic condition.

PMID- 20820088
TI  - Retroperitoneal malignant fibrous histiocytoma: case report.
AB  - OBJECTIVE: We present the case of a big retroperitoneal tumor that received the
      pathologic diagnosis of malignant fibrous histiocytoma. We also review the
      diagnostic and therapeutic features of this disease in the current literature.
      METHODS: We present the case of a 75-year-old male who was admitted to the
      Gastrointestinal Disease Department with asthenia of several months of evolution
      and gastrointestinal problems. Abdominopelvic CT scan revealed a big mass of 20 x
      22 x 12 cm, which seems to depend from the left kidney, together with an 8 cm
      diameter abdominal aortic aneurysm. RESULTS: The patient underwent surgery and
      left radical nephrectomy together with radical resection of the retroperitoneal
      mass were performed. Pathology reportes malignant fibrous histiocytoma of the
      storiform-pleomorphic type, with hyaline degeneration foci (stadium pT2B).
      CONCLUSIONS: Sarcomas are rare neoplasias. They can adopt several different
      morphologic patterns, as well as many differentiation degrees. The surgical
      treatment is still the only therapy with healing possibilities. Adjuvant
      treatments through radiotherapy and/or chemotherapy are brought into question.

PMID- 20820089
TI  - Images in urology. Bilateral calcification of deferent ducts.

PMID- 20820090
TI  - Bending of conjugated molecular wires and its effect on electron conduction
      properties.
AB  - The electronic structure and electron transport properties of simple conjugated
      molecular wires like oligophenylene ethynylene (OPE) and oligophenylene vinylene
      (OPV) are studied under compression. If artificially confined to a given shorter
      length, the oligomers tend to bend and bending causes a loss in the overlap of
      the conjugated molecular orbitals. Theoretical modeling of electronic transport
      has been carried out for all undistorted and compressed OPE/OPV oligomers. OPV
      exists in step-like or V-like conformations and they have the same stability with
      very similar frontier molecular orbitals. The conductances of these molecular
      wires are calculated when inserted between two gold probes and the conductances
      for OPV are found to be comparable to OPE when the interfaces are same. The
      conductance decreases with bending due to the gradual loss in overlap of the
      molecular orbitals. It is also found that the conductances of the molecular wires
      decrease very strongly if the terminal sulfur atom is simultaneously bonded to
      hydrogen and a gold surface, thus reflecting the importance of the interface in
      determining the conductance in two-probe systems. From the conductance studies it
      may be concluded that if one or more benzene rings of OPE are rotated from
      coplanar conditions, the orthogonal molecular orbitals may completely block the
      electronic transport, rendering the molecule insulating.

PMID- 20820091
TI  - Preparation of europium-quantum dots and europium-fluorescein composite
      nanoparticles available for ratiometric luminescent detection of metal ions.
AB  - The silica-encapsulated luminescent lanthanide nanoparticles have been developed
      for the selective tagging of a wide range of important targets in recent years,
      however, they are mainly limited to europium and terbium compounds. In this work,
      two types of europium-containing dual-luminophore silica nanoparticles, silica
      encapsulated CdTe quantum dots (CdTe QDs)-BHHCT-Eu(3+) complex nanoparticles and
      BHHCT-Eu(3+) surface-bound silica-encapsulated fluorescein isothiocyanate (FITC)
      nanoparticles (BHHCT: 4, 4'-bis(1'', 1'', 1'', 2'', 2'', 3'', 3''-heptafluoro
      4'', 6''-hexanedion-6''-yl)chlorosulfo-o-terphenyl), were successfully prepared
      using a water-in-oil (W/O) reverse microemulsion method. The results of
      transmission electron microscopy and luminescence spectroscopy characterizations
      indicate that the two types of nanoparticles are all monodisperse, spherical and
      uniform in size (approximately 50 nm in diameter), and have well-resolved and
      stable dual luminescence emission properties. The CdTe QDs-BHHCT-Eu(3+)
      nanoparticles can be excited at 365 nm to give dual-emission peaks at 535 and 610
      nm, and the FITC-BHHCT-Eu(3+) nanoparticles can be excited at 335 nm to give dual
      emission peaks at 515 and 610 nm. The luminescence response investigations of the
      nanoparticles to different metal ions indicate that the new nanoparticles can be
      used as ratiometric luminescent sensing probes for the selective detection of
      Cu(2+) and Fe(2+) ions, respectively. The performance of the nanoparticle probe
      for metal ion detection was investigated.

PMID- 20820092
TI  - The fabrication of thermoelectric La0.95Sr0.05CoO3 nanofibers and Seebeck
      coefficient measurement.
AB  - The P-type perovskite oxides La(1-x)Sr(x)CoO(3) are a promising group of complex
      oxide thermoelectric (TE) materials. The thermoelectric properties of these
      oxides are expected to be significantly improved when their critical dimensions
      are reduced to the nanoscale. In this paper, the La(0.95)Sr(0.05)CoO(3)
      nanofibers, with diameters in the range of approximately 35 nm, were successfully
      prepared by the electrospinning process. X-ray diffraction (XRD) and scanning
      electron microscopy (SEM) were used to characterize these thermoelectric
      nanofibers. A micro-electromechanical (MEMS) tester was designed and fabricated
      to measure the Seebeck coefficient of the nanofibers. The measured voltage output
      was as large as 1.7 mV and the obtained Seebeck coefficient of the nanofibers
      reached 650 microV K(-1).

PMID- 20820093
TI  - An insight into the metabolic responses of ultra-small superparamagnetic
      particles of iron oxide using metabonomic analysis of biofluids.
AB  - Ultra-small superparamagnetic particles of iron oxides (USPIO) have been
      developed as intravenous organ/tissue-targeted contrast agents to improve
      magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and
      effects on metabolism have attracted particular attention. In the present study,
      uncoated and dextran-coated USPIO were investigated by analyzing both rat urine
      and plasma metabonomes using high-resolution NMR-based metabonomic analysis in
      combination with multivariate statistical analysis. The wealth of information
      gathered on the metabolic profiles from rat urine and plasma has revealed subtle
      metabolic changes in response to USPIO administration. The metabolic changes
      include the elevation of urinary alpha-hydroxy-n-valerate, o- and p-HPA, PAG,
      nicotinate and hippurate accompanied by decreases in the levels of urinary alpha
      ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and
      acetate following USPIO administration. The changes associated with USPIO
      administration included a gradual increase in plasma glucose, N-acetyl
      glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone
      bodies (beta-hydroxybutyrate, acetone and acetoacetate) and individual amino
      acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and
      glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and
      triacylglycerol. Hence USPIO administration effects are reflected in changes in a
      number of metabolic pathways including energy, lipid, glucose and amino acid
      metabolism. The size- and surface chemistry-dependent metabolic responses and
      possible toxicity were observed using NMR analysis of biofluids. These changes
      may be attributed to the disturbances of hepatic, renal and cardiac functions
      following USPIO administrations. The potential biotoxicity can be derived from
      metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers
      a promising approach for the detection of subtle physiological responses on
      mammalian metabolism, and can be employed to investigate the potential adverse
      effects of other nanoparticles and nanomaterials on the environment and human
      health.

PMID- 20820094
TI  - Degradability of superparamagnetic nanoparticles in a model of intracellular
      environment: follow-up of magnetic, structural and chemical properties.
AB  - The unique magnetic properties of iron oxide nanoparticles have paved the way for
      various biomedical applications, such as magnetic resonance cellular imaging or
      magnetically induced therapeutic hyperthermia. Living cells interact with
      nanoparticles by internalizing them within intracellular acidic compartments.
      Although no acute toxicity of iron oxide nanoparticles has been reported up to
      now, the mechanisms of nanoparticle degradation by the cellular environment are
      still unknown. In the organism, the long term integrity and physical state of
      iron-based nanoparticles are challenged by iron homeostasis. In this study, we
      monitored the degradation of 7 nm sized maghemite nanoparticles in a medium
      mimicking the intracellular environment. Magnetic nanoparticles with three
      distinct surface coatings, currently evaluated as MRI contrast agents, were shown
      to exhibit different kinetics of dissolution at an acidic pH in the presence of a
      citrate chelating agent. Our assessment of the physical state of the
      nanoparticles during degradation revealed that the magnetic properties, size
      distribution and structure of the remaining nanocrystals were identical to those
      of the initial suspension. This result suggests a model for nanoparticle
      degradation with rapidly dissolved nanocrystals and a reservoir of intact
      nanoparticles.

PMID- 20820095
TI  - Parallel optical readout of cantilever arrays in dynamic mode.
AB  - Parallel frequency readout of an array of cantilevers is demonstrated using
      optical beam deflection with a single laser-diode pair. Multi-frequency
      addressing makes the individual nanomechanical response of each cantilever
      distinguishable within the received signal. Addressing is accomplished by
      exciting the array with the sum of all cantilever resonant frequencies. This
      technique requires considerably less hardware compared to other parallel optical
      readout techniques. Readout is demonstrated in beam deflection mode and
      interference mode. Many cantilevers can be readout in parallel, limited by the
      oscillators' quality factor and available bandwidth. The proposed technique
      facilitates parallelism in applications at the nano-scale, including probe-based
      data storage and biological sensing.

PMID- 20820096
TI  - The formulation, characterization and in vivo evaluation of a magnetic carrier
      for brain delivery of NIR dye.
AB  - This work reports the targeting of the near infrared (NIR) dye indocyanine green
      (ICG) to the brain using composite nanoparticles. Thermal decomposition of iron
      pentacarbonyl was used to synthesize monodisperse oleic acid coated magnetic
      nanoparticles (OAMNP). Synthesized OAMNP and ICG were encapsulated in a poly
      (lactide-co-glycolide) matrix using an emulsion evaporation method. Different
      batches containing OAMNP:PLGA ratios (1:4, 1:2 and 3:4) were prepared with ICG
      (group B-1, 2, 3) and without ICG (group A-1, 2, 3) loading. All the formulations
      were characterized in terms of morphology, particle size, zeta potential,
      magnetic content, ICG encapsulation efficiency and the spectral properties of
      ICG. The optimized formulation showed an encapsulation efficiency of 56 +/- 4.6%
      for ICG and 57 +/- 1.37% for OAMNP. The biodistribution and brain targeting study
      involved three groups of six animals, each with 0.4 mg kg(-1) equivalent of ICG,
      given as neat ICG solution, composite nanoparticles without the aid of a magnetic
      field, and composite nanoparticles under the influence of a magnetic field (8000
      G) to groups 1, 2 and 3 respectively. The tissue analysis and microscopy images
      revealed a significantly higher brain concentration of ICG (p < 0.05) for group 3
      than the two control groups. These results are encouraging for the brain delivery
      of hydrophilic dyes/drugs using this method for biomedical applications.

PMID- 20820097
TI  - Hierarchical paramecium-like hollow and solid Au/Pt bimetallic nanostructures
      constructed using goethite as template.
AB  - Novel hollow and solid paramecium-like hierarchical Au/Pt bimetallic
      nanostructures were constructed using goethite as template via a seed-mediated
      growth method. Transmission electron microscopy (TEM), xi-potential measurement,
      UV-vis spectroscopy, energy dispersive x-ray spectroscopy (EDS), ICP-AES
      measurement, x-ray powder diffraction (XRD) and x-ray photoelectron spectroscopy
      (XPS) were utilized to systematically characterize the bimetallic nanostructures.
      It is found that the core structure of the paramecium-like bimetallic
      nanomaterial is closely related to reducing agent. When ascorbic acid is used as
      reducing agent, goethite serves as in situ sacrificed template and hollow
      paramecium-like bimetallic structure is obtained. When NH(2)OH.HCl is used, solid
      nanostructure with preserved goethite core is produced. Heating the reaction
      solution is necessary to obtain the paramecium-like morphology with rough
      interconnected Pt cilia shell. The thickness of Pt cilia layer can be controlled
      by adjusting the molar ratio of H(2)PtCl(6) to Au nanoseeds. The overgrowth of
      the rough Pt cilia is proposed to be via an autocatalytic and three-dimensional
      heterogeneous nucleation process first through flower-like morphology. Both the
      hollow and solid hierarchical paramecium-like Au/Pt bimetallic nanostructures
      show good catalytic activities.

PMID- 20820098
TI  - High-performance dye-sensitized solar cells with gel-coated binder-free carbon
      nanotube films as counter electrode.
AB  - High-performance dye-sensitized solar cells (DSCs) with binder-free films of
      carbon nanotubes (CNTs), including single-walled CNTs (SWCNTs) and multi-walled
      CNTs (MWCNTs), as the counter electrode are reported. The CNT films were
      fabricated by coating gels, which were prepared by dispersing CNTs in low
      molecular-weight poly(ethylene glycol) (PEG) through mechanical grinding and
      subsequent ultrasonication, on fluorine tin oxide (FTO) glass. PEG was removed
      from the CNT films through heating. These binder-free CNT films were rough and
      exhibited good adhesion to substrates. They were used as the counter electrode of
      DSCs. The DSCs with SWCNT or MWCNT counter electrodes exhibited a light-to
      electricity conversion efficiency comparable with that with the conventional
      platinum (Pt) counter electrode, when the devices were tested immediately after
      device fabrication. The DSCs with an SWCNT counter electrode exhibited good
      stability in photovoltaic performance. The efficiency did not decrease after four
      weeks. On the other hand, DSCs with the MWCNT or Pt counter electrode exhibited a
      remarkable decrease in the photovoltaic efficiency after four weeks. The high
      photovoltaic performance of these DSCs is related to the excellent
      electrochemical catalysis of CNTs on the redox of the iodide/triiodide pair, as
      revealed by the cyclic voltammetry and ac impedance spectroscopy.

PMID- 20820099
TI  - Controlled morphology of aluminum alloy nanopillar films: from nanohorns to
      nanoplates.
AB  - Nanopillar films of Al-Nb alloys have been fabricated on substrates with a
      regular concave cell structure by oblique angle physical vapor deposition. The
      concave cell structure of the substrate increases the shadow region for the flux
      of depositing atoms, assisting the formation of an isolated nanopillar on each
      cell. Depending upon the alloy composition and deposition angle, the pillar shape
      changes from horn-like nanopillars through triangular nanoprisms to nanoplates.
      The Al-Nb alloy nanoplate films with wide gaps between plates are of interest as
      electrodes for capacitor applications. The dielectric oxide film formed on the
      nanoplate film showed a capacitance more than ten times larger than that on the
      respective flat film, due to the enlarged surface area.

PMID- 20820100
TI  - Specificity in killing pathogens is mediated by distinct repertoires of human
      neutrophil peptides.
AB  - Neutrophil-derived antimicrobial peptides and proteins (AMPs) play an important
      role in the defense against microbes. Absence of defense is illustrated by
      neutropenic patients with frequent bacterial and fungal infections. However, the
      specificity of the antimicrobial effects has not been adequately described. We
      set out to determine the specific antimicrobial pattern of polypeptides in
      neutrophils (polymorphonuclear leukocytes, PMNs) against 4 potential human
      pathogens: Moraxella catarrhalis, Staphylococcus aureus, Haemophilus influenzae
      and Candida albicans. Protein extracts of human PMNs were separated using high
      performance liquid chromatography and fractions were assayed for antimicrobial
      activity. Fractions displaying antimicrobial activity were separated on SDS-PAGE
      and characterized using MALDI-MS. Depletion experiments were utilized to
      determine the contribution of each AMP to the antimicrobial effect. Among the
      identified AMPs, alpha-defensins 1-3, azurocidin, LL-37, lysozyme, calprotectin
      and lactotransferrin were studied in detail. We found a divergent pattern of
      killing, that is, certain peptides and proteins exhibited selective activity
      against specific pathogens, while others displayed a broader antimicrobial
      activity. alpha-Defensins, LL-37 and calprotectin were active against all
      species, while lactotransferrin exclusively inhibited growth of S. aureus.
      Conversely, azurocidin was active against all species except S. aureus. Our
      observations may shed light on bacterial resistance to AMPs and on the
      elimination of specific bacterial communities on mucosal surfaces.

PMID- 20820101
TI  - Hyaluronan used for intradermal injections is incorporated into the pericellular
      matrix and promotes proliferation in human skin fibroblasts in vitro.
AB  - BACKGROUND: Over the past decade injectable hyaluronan (HA) formulations have
      been widely used to decrease the visibility of skin aging. However, little basic
      research has been performed to address their effect on dermal skin fibroblasts.
      OBJECTIVE: The aim of the present study was to investigate whether human skin
      fibroblasts are affected by exogenous non-cross-linked HA with respect to
      proliferation, migration and extracellular matrix composition. METHODS: The
      effect of a non-cross-linked HA on proliferation, migration and gene expression
      of human dermal fibroblasts was determined. Furthermore, affinity histochemistry
      of pericellular HA was performed. RESULTS: Proliferation was significantly
      stimulated by HA whereas migration was not affected. Importantly, exogenous HA
      was incorporated into fine HA filaments of the pericellular fibroblast matrix.
      CONCLUSION: This is the first evidence that a HA formulation used in humans for
      cosmetic reasons stimulates fibroblast proliferat

PMID- 20820102
TI  - Maternal smoking, obesity and male fetal sex predispose to a large nuchal
      translucency thickness in healthy fetuses.
AB  - OBJECTIVES: Our aim was to evaluate the effect of fetal sex, smoking and body
      mass index (BMI) on nuchal translucency (NT). METHODS: We analyzed data from
      7,357 women with a normal singleton live birth outcome with information on
      smoking, BMI and sex of the infant. NT measurements were converted to multiples
      of the median (MoM(NT)) using a previously reported linear regression analysis.
      RESULTS: The odds ratio (OR) for MoM(NT) >95th centile was 1.5 (95% CI 1.2-1.9)
      for smokers compared to nonsmokers and 1.4 (95% CI 1.1-1.7) for male fetuses
      compared to female fetuses. Obese women (BMI >=30) had an increased OR for a
      large NT of 1.7 (95% CI 1.2-2.6) compared to normal weight women. Obese smokers
      carrying a male fetus had an OR of 4.2 (95% CI 1.7-10.1) of a MoM(NT) >95th
      centile compared to normal weight nonsmoking women with a female fetus. The
      effects of smoking, obesity status and fetal sex were independent of each other.
      CONCLUSIONS: Smoking, obesity and male sex are associated to a MoM(NT) >95th
      centile. This may affect screening performance and entail unnecessary anxiety in
      these women. Further investigations, including fetuses with adverse outcome, are
      needed.

PMID- 20820103
TI  - Chromophobe renal cell carcinoma with osteosarcoma differentiation: case report
      and literature review.
AB  - Chromophobe renal cell carcinoma is a distinct subtype of renal cell carcinoma
      that is well known for its relatively good prognosis. When it presents with
      sarcomatoid differentiation, necrosis of the sarcomatoid area or angiolymphatic
      invasion, it becomes a highly aggressive neoplasm. The presence of osteosarcoma
      like elements in sarcomatoid chromophobe renal cell carcinoma is very rare as
      only 5 cases have been reported previously. We present a 6th case of sarcomatoid
      chromophobe renal cell carcinoma, which had an osteosarcoma differentiation
      component. However, the correlation between the presence of heterologous elements
      and prognosis is unknown because of the rarity of this phenomenon.

PMID- 20820104
TI  - Chronic pruritus management: a plea for improvement--can itch clinics be an
      option?

PMID- 20820105
TI  - Natalizumab and beyond.

PMID- 20820106
TI  - Brain imaging modality before systemic thrombolysis for ischemic stroke within
      three hours.
AB  - OBJECTIVE: In Japan, MRI-based thrombolysis after CT screening is the most common
      imaging strategy prior to intravenous thrombolysis (IVT) with tissue plasminogen
      activator (tPA) within 3 h after ischemic stroke. A choice of MRI with MR
      angiography (MRA) provides a higher diagnostic accuracy, but may delay an
      initiation of thrombolysis. METHODS: In our neuro-unit, brain CT is the first
      screening image for suspected stroke. We retrospectively examined a delay to
      thrombolysis, imaging modality, diagnostic accuracy, and clinical outcomes at 3
      months by the modified Rankin Scale in patients receiving IVT within 3 h.
      RESULTS: Among 67 patients receiving IVT with tPA, brain imaging prior to IVT was
      solely CT in 10 (15%) patients and CT + MRI/MRA in 57 (85%) patients. Final
      diagnosis of brain ischemia was 100%. Patients receiving CT + MRI had
      significantly shorter pre-hospital delay (mean 54 vs. 83 min; p = 0.012), but
      longer door-to-needle time (mean 90 vs. 57 min; p = 0.019) than those receiving
      CT only. Finally, time from onset to thrombolysis was not different between the
      two groups and clinical outcomes were also comparable. The earlier patients
      arrived, the longer door-to-needle times were (p < 0.001). CONCLUSIONS: The
      imaging strategy of initial CT screening with optional MRI/MRA scans prior to IVT
      was feasible. However, it resulted in an additional 30 min in-hospital delay of
      tPA administration, which may affect clinical outcomes.

PMID- 20820109
TI  - Disorders of sex development (DSD). Preface.

PMID- 20820108
TI  - Drug-disease interaction: reduced verapamil response in isoproterenol-induced
      myocardial injury in rats.
AB  - Inflammation is involved in the pathogenesis of cardiovascular diseases. We
      investigated whether the response to verapamil is altered in experimental acute
      myocardial injury (AMI). Two groups of male Sprague-Dawley rats (230-280 g) were
      divided into control (n = 8) and post-AMI (n = 13). Myocardial injury was induced
      by 2 daily doses of 150 mg.kg(-1) isoproterenol (ISP). Subcutaneous ECG leads
      were implanted, and 2 days following the second injection, each rat was dosed
      with 25 mg.kg(-1) verapamil per os, and an ECG was recorded over 4 h after
      dosing. The animals were euthanized and blood samples collected for analysis of
      inflammatory mediators and cardiac troponin I (cTnI). Cardiac L-type calcium
      channel (Ca(v)1.2) protein levels and mRNA were determined by Western blot and
      real-time PCR, respectively. ISP treatment caused a 170% increase in serum cTnI,
      J point elevation, R wave amplitude reduction and Q wave development. Cardiac
      injury caused a 75% reduction in verapamil potency by prolonging the PR interval
      and reducing the heart rate. Cardiac tissue injury also caused a significant
      reduction in the Ca(v)1.2 protein level. Verapamil response was significantly
      correlated with cTnI. The reduced potency of verapamil in myocardial injury
      appears to result from a reduction in the drug target protein Ca(v)1.2. If
      extrapolated to humans, our observations may suggest that downregulation of
      calcium channel proteins is a contributory factor in the poor outcome in
      myocardial infarction.

PMID- 20820111
TI  - Bone health in disorders of sex differentiation.
AB  - Sex steroids are main regulators of skeletal growth, maturation and mass in both
      men and women. People with disorders of sex development (DSD) may experience
      problems in developing normal bone growth, structure and mass, because abnormal
      sex steroid secretion or action may be operative. In complete androgen
      insensitivity syndrome several reports documented reduced bone mineral density
      (BMD). Reduced BMD is evident in patients with not removed or removed gonads, but
      it is poorer in the latter, mainly when compliance with estrogen replacement
      therapy is not guaranteed. Large impairment of BMD does not seem to be present in
      patients with partial androgen insensitivity syndrome or 5alpha-reductase-2
      deficiency, providing that gonads are not removed or that substitutive therapy is
      optimized. In congenital adrenal hyperplasia, BMD may be impaired as a result of
      not optimal glucocorticoid administration. In Turner syndrome, impaired BMD may
      result from the combined actions of estrogen deficiency, low bone dimensions,
      altered bone geometry, deficient cortical bone, and trabecular bone loss. Optimal
      estrogen administration seems to be important in preserving bone mass and
      enhancing trabecular bone volume. On the whole, bone health represents a main
      clinical issue for the management of persons with disorders of sex
      differentiation, and well designed longitudinal studies should be developed to
      improve their bone health and well-being.

PMID- 20820110
TI  - New technologies for the identification of novel genetic markers of disorders of
      sex development (DSD).
AB  - Although the genetic basis of human sexual determination and differentiation has
      advanced considerably in recent years, the fact remains that in most subjects
      with disorders of sex development (DSD) the underlying genetic cause is unknown.
      Where pathogenic mutations have been identified, the phenotype can be highly
      variable, even within families, suggesting that other genetic variants are
      influencing the expression of the phenotype. This situation is likely to change,
      as more powerful and affordable tools become widely available for detailed
      genetic analyses. Here, we describe recent advances in comparative genomic
      hybridisation, sequencing by hybridisation and next generation sequencing, and we
      describe how these technologies will have an impact on our understanding of the
      genetic causes of DSD.

PMID- 20820112
TI  - Intervention with costimulatory pathways as a therapeutic approach for graft
      versus-host disease.
AB  - Graft-versus-host disease (GVHD) is mediated by mature donor T cells contained in
      the hematopoietic stem cell graft. During the development of GVHD, signaling
      through a variety of costimulatory receptors plays an important role in
      allogeneic T cell responses. Even though delivery of costimulatory signals is a
      prerequisite for full activation of donor T cells in the phase of their
      interactions with host APCs, their involvement with GVHD might occur over
      multiple stages. Like many other aspects of GVHD, promise of therapeutic
      interventions with costimulatory pathways has been gleaned from preclinical
      models. In this review, I summarize some of the advances in roles of
      costimulatory molecules in GVHD pathophysiology and discuss preclinical
      approaches that warrant further exploration in the clinic, focusing on novel
      strategies to delete pathogenic T cells.

PMID- 20820113
TI  - [Development of a web-based education program for nurses working in nursing homes
      on human rights of older adults].
AB  - PURPOSE: This study was done to develop a web-based education program for nurses
      working in nursing homes. The focus was on the rights of older adults. METHODS:
      The program was designed based on the Network-Based Instructional System Design
      (NBISD) model and was operated and evaluated between July 2007 and June 2008.
      RESULTS: Out of nursing records of 40 residents from a nursing home, the final 7
      cases were deducted through classification using the Resource Utilization Group
      (RUG)-III. The data on needs for education was collected from 28 nurses working
      in 15 nursing homes located in Seoul and Gyeonggi Province, who agreed to
      complete a self-report questionnaire. A comprehensive review of the literature
      and two focus groups interviews were used to search for risk factors and
      guidelines for protection of human rights. The education program was developed
      based on Kolb's experiential learning model and composed of 5 units, which
      included content on types of human rights and rights to death with dignity, elder
      abuse, physical liberty, and self-determination. The program was positively
      evaluated showing a score of 3.35 (SD=0.37) out of 4. CONCLUSION: The educational
      program developed in this study should promote nurses' sensitivity to the rights
      of elders and improve nurses' behaviors in protecting the rights of elders
      residing in nursing homes.

PMID- 20820114
TI  - [Effects of oral care with essential oil on improvement in oral health status of
      hospice patients].
AB  - PURPOSE: This study was done to examine the effects of oral care with essential
      oil in improving the oral health status of hospice patients with terminal cancer.
      METHODS: The participants were 43 patients with terminal cancer admitted to K
      hospital in G city, Korea. Twenty-two patients were assigned to the experimental
      group and 21 to the control group. Participants in the experimental group
      received special mouth care with essential oil (application of essential oil
      mixture consisting of geranium, lavender, tea tree, and peppermint). The control
      group received special mouth care with 0.9% saline. The special mouth care was
      performed twice daily for one week in both groups. The scores for subjective oral
      comfortness, objective oral state, and numbers of colonizing Candida albicans
      were measured before and after the treatment. RESULTS: The score for subjective
      oral comfortness and objective oral state were significantly higher in the
      experimental group compared to the control group. The numbers of colonizing
      Candida albicans significantly decreased in the experimental group compared to
      the control group. CONCLUSION: Oral care with essential oil could be an effective
      oral health nursing intervention for hospice patients with terminal cancer.

PMID- 20820115
TI  - [An analysis of the meaning of respite for family caregivers of elderly with
      dementia].
AB  - PURPOSE: This study was a qualitative research study in which focus group
      interviews were used to collect data on the meaning of respite for family
      caregivers who are taking care of elders with dementia. METHODS: The focus group
      interviews and participants consisted of 2 family caregiver groups, for a total
      of 8 people taking care of their elders and 5 professional caregivers working in
      a geriatrics hospital or social welfare institutions. Content analysis was used
      and debriefing notes were referred in order to analyze the data. RESULTS: The
      meaning of respite in this research was measured using 4 main categories:
      'Temporary break from routine', 'direct help', 'psychological comfort',
      'valuables which cannot be taken easily' and 9 subcategories: 'Temporary
      diversion of attention', 'temporarily free from my duty', 'taking care of
      oneself', 'receiving economic help', 'empathize with others', 'comfort based on
      trust', 'resting together with the elder', 'no time to rest', 'cannot get out of
      one's obligatory duty'. CONCLUSION: The findings of the study show that rest
      means not only a temporary relief from caretaking, but also a real respite based
      on the patients' stable state and comfort. These results indicate a new meaning
      for respite, that the first step of respite program has to begin even when the
      caregivers do not recognize the need for respite.

PMID- 20820116
TI  - [Effects on couples' communication, intimacy, conflict and quality of life by
      foot massage between immigrants].
AB  - PURPOSE: The purpose of this study was to evaluate the effects on immigrant
      couples' communication, intimacy, conflict and quality of life when using foot
      massage. METHODS: The research design consisted of pre-and-post test consecutive
      experimental design through a nonequivalent control group. Data were collected
      July 6, 2009 to February 27, 2010. The 36 couples were divided into two groups,
      experimental and control with 18 couples in each group. Foot massage was applied
      twice a week for 6 weeks by the couples in the experimental group. RESULTS: There
      were statistically significant increases in communication (p=.011), intimacy
      (p<.001), quality of life (p=.017) between the couples in the experimental group
      compared to the control group. There was also a statistically significant
      decrease in conflict (p=.003) between the couples in the experimental group
      compared to the control group. CONCLUSION: Foot massage can be applied as a
      nursing intervention for improvement of marital relationship in immigrant
      couples.

PMID- 20820117
TI  - [The changing pattern of physical and psychological health, and maternal
      adjustment between primiparas who used and those who did not use Sanhujori
      facilities].
AB  - PURPOSE: The purpose of this study was to compare levels of postpartum fatigue,
      depression, childcare stress, and maternal identity according to postpartum
      period between primiparas who used Sanhujori facilities and those who did not.
      METHODS: The research design was a longitudinal descriptive study using self
      report questionnaires. Participants were 55 healthy primiparas who delivered at
      one of 3 hospitals in Chungnam, 21 using Sanhujori facilities and 34 not using
      these facilities during the first three weeks after childbirth. Data were
      collected from October 2008 to April 2009 at three measurement points, 2-4 days
      after childbirth (T1), 4-6 weeks (T2), and 12-14 weeks (T3). Data were analyzed
      using the SPSS 17.0 WIN program. RESULTS: There was a significant difference in
      childcare stress between the two groups at 4-6 weeks after childbirth. Postpartum
      depression and childcare stress at 4-6 weeks were significantly higher than those
      of the other postpartum periods, while maternal identity was significantly lower.
      CONCLUSION: Child care stress is the most important issue among women who use
      Sanhujori facilities and the 4-6 week period after childbirth is very difficult
      to primiparas. These results indicate that nursing interventions for primiparas
      in Sanhujori facilities should focus on reducing childcare stress. Furthermore
      proper follow-up programs at 4-6 weeks are needed to decrease the difficulties in
      adjustment by new mothers.

PMID- 20820118
TI  - [Educational needs assessment on research ethics among nursing researchers].
AB  - PURPOSE: This study aimed to investigate the educational needs of research ethics
      among nursing researchers. METHODS: Convenience sample of 161 nursing professors
      and 262 master or doctoral nursing students participated in the study. Data was
      collected with self-reported questionnaire from June to August 2009, and analyzed
      with descriptive statistics using SPSS WIN (version 14.0). RESULTS: Among 161
      nursing professors, about 31.7% has educated nursing ethics in the postgraduate
      course. The most common course was nursing research or methodology (62.7%), and
      median education time was 2 hr. Areas that showed difficulty in understanding was
      the conflict of interest and plagiarism for professors and falsification and
      fabrication for graduate students. Average knowledge on the research ethics was
      75.4 points for professors and 61.6 points for students based on the 100 points.
      CONCLUSION: Educational needs of research ethics among nursing professors and
      students in the postgraduate course was high. We recommend both basic and
      advanced research ethics educational programs for the nursing researchers. The
      basic course should be at least 6 hr and include various cases and something to
      discuss.

PMID- 20820119
TI  - [Relationship of social support and meaning of life to suicidal thoughts in
      cancer patients].
AB  - PURPOSE: This study was done to explore the relationship of social support and
      meaning of life to suicidal thoughts among patients with cancer. METHODS: Data
      were collected by questionnaires from 138 patients who had been in cancer
      treatment at medical clinics and 8 patients who were members of an internet
      cancer association. The data were collected between August and November 2009 and
      analyzed using SPSS 12.0. RESULTS: Of the participants, 47.3% reported having had
      suicidal thoughts and 16.4% had attempted suicide since the diagnosis of cancer.
      The study participants received most support from family members, but 73.3%
      reported experiencing an existential vacuum. The suicide attempt group had
      significantly higher scores according to gender, age, level of education,
      diagnosis, treatment modality, level of activity, caregiver and social support
      compare to the suicide thought group. Suicidal thoughts were negatively related
      to social support and meaning of life was positively associated with social
      support. Support from family and friends and diagnosis explained 50.0% of
      variance for suicidal thoughts with 36.0% of variance being explained by family
      support. CONCLUSION: Nurses should be able to identify risk factors for suicide
      in cancer patients. Prevention and intervention efforts need to be directed
      toward improving social support, family support in particular, and assisting
      patients finding meaning in life after a diagnosis of cancer.

PMID- 20820120
TI  - [Structural equation modeling on quality of life in stroke survivors].
AB  - PURPOSE: This study was designed to test structural equation modeling of the
      quality of life of stroke survivors in order to provide guidelines for
      development of interventions and strategies to improve their quality of life.
      METHODS: The participants in the study were patients who visited the neurology
      outpatient department of a tertiary hospital in Seoul between June 25 and October
      15, 2009. Data collection was carried out through one-on-one interviews.
      Demographic factors, functional independence, social support, nutritional status,
      post-stroke biobehavioral changes and quality of life were investigated. RESULTS:
      The final analysis included 215 patients. Fitness of the hypothetical model was
      appropriate (chi(2)=111.5, p=.000, GFI=.926, AGFI=.880, RMSA=.068, NFI=.911,
      CFI=.953). Functional dependency, social support and post-stroke biobehavioral
      changes were found to be significant explaining variance in quality of life. Post
      stroke biobehavioral changes had the strongest direct influence on quality of
      life. Nutritional status had an indirect effect on the quality of life.
      CONCLUSION: To improve the quality of life of stroke survivors, comprehensive
      interventions are necessary to manage post-stroke biobehavioral changes, and
      strengthening social support networks that can contribute to enhancing the
      quality of life of stroke survivors.

PMID- 20820121
TI  - [Factors influencing depression in elderly people living at home].
AB  - PURPOSE: This study was done to identify the factors which influence depression
      for elderly people who live at home. METHODS: The participants were 134 elderly
      people living at home in M city. Data were collected from April 2 to 30, 2009 and
      analyzed using SPSS/WIN 12.0 and AMOS 5.0 program. I assumed path coefficients by
      doing path analysis to understand synthetically causal relationship which
      influences on depression. RESULTS: Social support, sleep pattern and self esteem
      had significant direct effects on life satisfaction and accounted for 50% of the
      total variance in life satisfaction. Physical symptoms, sleep pattern and life
      satisfaction also had significant direct effects on depression and accounted for
      59% of the variance in depression. But social support, self assertiveness and
      self esteem were not significant for depression. CONCLUSION: These results
      provide guidance for designing useful strategies to reduce depression in elderly
      people living at home.

PMID- 20820122
TI  - [Psychometric evaluation of a need scale for cancer patients undergoing follow-up
      care].
AB  - PURPOSE: The purpose of this present study was to develop and evaluate the
      psychometric properties of a needs scale for patients with cancer undergoing
      follow-up care (NS-C). METHODS: A preliminary NS-C of 48 was derived from
      literature reviews and in-depth interviews with patients with cancer. Content
      validation of the items was established by oncology physicians and nurses. Each
      item was scored on a five-point Likert scale. The preliminary NS-C and Eastern
      Cooperative Oncology Group (ECOG) performance status questionnaires were
      administered to 873 patients with cancer recruited from three university
      hospitals. The data were analyzed using factor analysis, multidimensional scaling
      analysis, ANOVA, Pearson correlation coefficients, and Cronbach's alpha. RESULTS:
      From the factor analysis, 25 significant items in six subscales were derived. The
      subscales were named physical symptoms, diet and exercise, support, relationship
      with health professionals, treatment/prognosis, and keeping mind under control.
      The NS-C also established item convergent and discriminant validity, and known
      groups validity. Cronbach's alpha of the subscales ranged from .90 to .92.
      CONCLUSION: This study suggests that the NS-C is an easy, reliable and valid
      instrument to measure the needs of patients with cancer. Health professionals may
      use the NS-C for patients with cancer both in practice and research.

PMID- 20820123
TI  - [Evaluation of mental status in high-risk neonates using infants coma scale].
AB  - PURPOSE: This was a cross sectional descriptive study to introduce the Infants
      Coma Scale (ICS), describe mental status of high risk infants using ICS and
      explore the relationships between ICS and clinical variables in infants
      hospitalized in a neonatal intensive care unit of a university hospital in Korea.
      METHODS: After ICS was developed and tested by the authors, a research nurse
      evaluated the mental status of the infants using the English version of ICS and
      obtained clinical information on the infants from their medical records. RESULTS:
      Data from 88 infants were analyzed. About 60% were male, 90% were preterm births,
      and 40% had pathologic abnormalities. Their mean gestational age was 32.4 (+/
      3.50) weeks and the mean birth weight was 1,842 (+/-728.6) grams. The Cronbach's
      alpha for the ICS was .78. There was a statistically significant positive
      correlation between ICS total score and five clinical variables including
      gestational age, birth weight, 1 and 5 min Apgar scores and respiration status.
      CONCLUSION: Mental status is an important parameter in nursing assessment. ICS is
      a valid and reliable instrument, which clinicians can easily use to evaluate the
      mental status of high risk infants.

PMID- 20820124
TI  - [Effects of a Taegyo program on parent-fetal attachment and parenthood in first
      pregnancy couples].
AB  - PURPOSE: The purpose of this study was to explore the effects of a Taegyo program
      on parents-fetal attachment and parenthood in first pregnancy couples (mothers
      and spouses). METHODS: The research design was a nonequivalent control group
      pretest-posttest experiment. Study participants were 52 first pregnancy couples
      visiting two medium-scale obstetrics and gynecology clinics located in Gwangju. A
      total of 52 couples were assigned to the experimental group (25 couples) and the
      control group (27 couples). The experimental couples were provided with a Taegyo
      program for 4 weeks. Data were analyzed by chi square test, t-test, and ANCOVA
      using the SPSS program. RESULTS: Post-treatment maternal-fetal attachment,
      paternal-fetal attachment and motherhood significantly increased in the
      experimental group as compared to the control group, but post-treatment
      fatherhood, anxiety, blood pressure and pulse of participants in the experimental
      group showed no significant difference from those in the control group.
      CONCLUSION: From these results, it is suggested that the Taegyo program has
      beneficial effects in enhancing parent-fetal attachment and motherhood in first
      pregnancy couples. Therefore, a Taegyo program can be recommended as a nursing
      intervention program for first pregnancy couples.

PMID- 20820125
TI  - [Effect of decreased locomotor activity on hindlimb muscles in a rat model of
      Parkinson's disease].
AB  - PURPOSE: The purpose of this study was to examine effects of decreased locomotor
      activity on mass, Type I and II fiber cross-sectional areas of ipsilateral and
      contralateral hindlimb muscles 21 days after establishing the Parkinson's disease
      rat model. METHODS: The rat model was established by direct injection of 6
      hydroxydopamine (6-OHDA, 50 microg) into the left substantia nigra after
      stereotaxic surgery. Adult male Sprague-Dawley rats were assigned to one of two
      groups; the Parkinson's disease group (PD; n=17) and a sham group (S; n=8).
      Locomotor activity was assessed before and 21 days after the experiment. At 22
      days after establishing the rat model, all rats were anesthetized and soleus and
      plantaris muscles were dissected from both ipsilateral and contralateral sides.
      The brain was dissected to identify dopaminergic neuronal death of substantia
      nigra in the PD group. RESULTS: The PD group at 21 days after establishing the
      Parkinson's disease rat model showed significant decrease in locomotor activity
      compared with the S group. Weights and Type I and II fiber cross-sectional areas
      of the contralateral soleus muscle of the PD group were significantly lower than
      those of the S group. CONCLUSION: Contralateral soleus muscle atrophy occurs 21
      days after establishing the Parkinson's disease rat model.

PMID- 20820126
TI  - [Fall risk in low-income elderly people in one urban area].
AB  - PURPOSE: The purpose of this study was to investigate the factors that increase
      of the risk for falls in low-income elders in urban areas. METHODS: The
      participants were elderly people registered in one of public health centers in
      one city. Data were collected by interviewing the elders, assessing their
      environmental risk factors, and surveying relevant secondary data from the public
      health center records. For data analysis, descriptive statistics and multiple
      logistic regression were performed using SPSS version 14. RESULTS: Stroke,
      diabetes, visual deficits, frequency of dizziness, use of assistive devices and
      moderate depression were statistically significant risk factors. The comorbidity
      of chronic diseases with other factors including depression, visual deficit,
      dizziness, and use of assistive devices significantly increased the risk of
      falls. From multiple logistic regression analysis, statistically significant
      predictors of falls were found to be stroke, total environmental risk scores,
      comorbidity of diabetes with visual deficits, and with depression. CONCLUSION:
      Fall prevention interventions should be multifactorial, especially for the elders
      with stroke or diabetes, who were identified in this study as the high risk group
      for falls. A fall risk assessment tool for low-income elders should include both
      the intrinsic factors like depression, dizziness, and use of assistive devices,
      and the extrinsic factors.

PMID- 20820127
TI  - [Development and evaluation of a transitional care program for patients
      discharged from military hospitals].
AB  - PURPOSE: The purpose of this study was to develop and evaluate a transitional
      care program for patients discharged from military hospitals. The study consists
      of two phases: developing the program and evaluating its effectiveness. METHODS:
      The conceptual framework used to guide the development of the program was
      Meleis's transition theory. A quasi-experimental design was employed for this
      study. Participants were recruited from patients discharged from one military
      hospital, 72 in the control group and 56 in the experiment group. Data were
      analyzed using SPSS WIN 12.0 program with chi-square, Fisher's exact test,
      independent t-test, and mixed model. RESULTS: Participants in the transitional
      care program reported promoting a positive personal condition, and more healthy
      patterns of response in the first week after being discharged and a smoother
      discharge transition. CONCLUSION: The transitional care program developed for
      discharge patients from military hospital promoted discharge readiness and
      promoted smooth discharge transition.

PMID- 20820128
TI  - Energy cost and cardiovascular response to upper and lower limb rhythmic exercise
      with different equipments in normal-weight and severely obese individuals.
AB  - AIMS: The purpose of the study was to assess energy expenditure and
      cardiovascular response to rhythmic activity with 6 machines exercising different
      arm and leg muscle groups in normal-weight (NW) and obese (OB) individuals.
      METHODS: In 16 extremely OB subjects and 15 NW controls, oxygen uptake (VO2),
      heart rate (HR), blood lactate (LA) concentration and ratings of perceived
      exertion (RPE) were determined during submaximal rhythmic exercise at different
      intensities obtained by increasing the frequency of the movement (FOM) with each
      machine. Peak VO2 (VO2p) for each equipment was determined with incremental tests
      up to exhaustion, whereas maximal VO2 was estimated at cycle ergometer. RESULTS:
      Net energy cost (Enet) of exercise increased (p<0.001) for effect of FOM, in both
      NW and OB with all equipments. Enet was higher in OB than NW during submaximal
      exercise with Chest/Back, Shoulder Press/Lat Pull, and Leg Press. Higher VO2p
      were attained with lower limbs than with upper limbs, in both NW (p<0.001) and OB
      (p<0.001). At the same VO2 (relative to maximal), HR, LA, and RPE were similar in
      NW and OB but higher during arm than leg activity (p<0.001), while at the same
      VO2 (relative to VO2p) no difference was detected. CONCLUSION: Enet of rhythmic
      exercise is higher in OB than NW with machines requiring wide displacement of
      large body segments. For both NW and OB, physiological responses and RPE are
      importantly affected by the relative activation of involved muscles. LA
      concentration is an important determinant of RPE, independent of the limb in
      activity.

PMID- 20820129
TI  - Clinical aggressiveness of incidental and non-incidental thyroid cancer.
AB  - BACKGROUND: With the increasing use of thyroid ultrasound, the recognition of
      thyroid nodules in a large proportion of apparently healthy subjects has become
      common. Because also the papillary thyroid microcarcinomas (PTMC) are being
      increasingly discovered, it is important to ascertain whether PTMC may exhibit
      heterogenous clinical features, associated with different aggressiveness. AIM: We
      retrospectively examined 122 subjects [98 female (80.3%), and 24 male (19.7%)]
      with thyroid cancer to find potential clinical and pathological findings that
      could be predictive of clinically aggressive behavior. RESULTS: Twenty of the 31
      patients with true incidental cancer (64.5%) in comparison to 20 of the 91
      patients with non-incidental cancer (21.9%) had a diameter <10 mm, and this
      difference was statistically significant (p<0.0001). There was a statistically
      significant association between size and invasiveness because 19.3% of invasive
      cancers were <10 mm whereas 44.6% of non-invasive cancers were <10 mm (p=0.005).
      The relationship between incidental discovery and invasiveness was also
      evaluated, but the proportion of incidental invasive cancer (19.3%) was not
      significantly different from that of incidental non-invasive cancer (30.8%). In
      the multivariate analysis, only size <10 mm (odds ratio=0.35, p=0.013) and
      papillary vs other histotypes (odds ratio=0.35, p=0.04) were statistically
      significant protective factors against invasiveness. CONCLUSIONS: a) Incidentally
      discovered thyroid cancers are more frequently microcarcinomas; b) there appears
      to be no difference in terms of invasive behavior between incidental and non
      incidental thyroid cancer; c) smaller tumor size emerges as a protective factor.

PMID- 20820130
TI  - Growth hormone and lactate responses induced by maximal isometric voluntary
      contractions and whole-body vibrations in healthy subjects.
AB  - BACKGROUND: In contrast with maximal voluntary resistance exercise, which is
      allegedly considered a potent GH stimulus in young subjects, evaluation of GH
      response to whole-body vibrations (WBV) has yielded conflicting results. METHODS:
      The acute effects of WBV alone (test A), maximal voluntary isometric contractions
      (MVC) (test B), and combination of WBV and MVC (test C) on serum GH and blood
      lactate (LA) levels were studied in 9 healthy adult males. Muscle soreness was
      assessed 24 and 48 h after exercise by a visual analogue scale. RESULTS: GH
      responses were significantly higher after tests B and C than after test A (GH
      peaks: 18.8 +/- 9.5 ng/ml or 20.8 +/- 13.7 ng/ml, respectively, vs 4.3 +/- 3.5
      ng/ml; p<0.05), with no difference between tests B and C. LA concentrations
      significantly increased after tests A, B, and C, being significantly higher after
      tests B and C than after test A (LA peaks: 2.0 +/- 0.5 mmol/l or 6.7 +/- 2.3
      mmol/l, respectively, vs 7.6 +/- 0.9 mmol/l; p<0.05). Peak LA values were
      significantly correlated to GH peaks in the 3 tests (r=0.48; p<0.05). Muscle
      soreness was significantly higher 24-48 h after tests B and C than after test A,
      no significant differences being present between tests B and C. CONCLUSIONS: WBV
      stimulates GH secretion and LA production, with no additive effect when combined
      with repeated isometric voluntary contractions. Optimization of protocols based
      on WBV seems important to maximize the positive effects of this intervention on
      the somatotropic function.

PMID- 20820133
TI  - [Recent advance in the treatment of Churg Strauss syndrome].

PMID- 20820134
TI  - [Indications of biologics, especially anti-TNF-alpha antibodies, for the
      treatment of psoriasis].

PMID- 20820131
TI  - Association of increased parathyroid hormone with neuroendocrine activation and
      endothelial dysfunction in elderly men with heart failure.
AB  - High PTH levels have been reported in patients with chronic heart failure (CHF).
      Similarly, its levels increase with aging and are related to impaired survival in
      elderly adults. However, its relationship with neuroendocrine activation and
      endothelial dysfunction in CHF has not been previously studied. Seventy-three CHF
      males with New York Heart Association (NYHA) classes II and III and 20 control
      subjects aged >= 55 yr were recruited. PTH, 25-hydroxyvitamin D [25(OH)D], N
      terminal pro-brain natriuretic peptide (NT-pro-BNP), adiponectin, and
      osteoprotegerin were measured. Endothelial function (brachial flow mediated
      dilation), echocardiography, physical performance, and quality of life were
      assessed, as well. CHF patients had markedly increased serum PTH (77 +/- 33 vs 40
      +/- 11 pg/ml, p<0.0001), NT-pro-BNP [1809 (2742) vs 67 (74) pg/ml, p<0.0001],
      adiponectin (17 +/- 9 vs 10 +/- 2 MUg/ml, p<0.0001), osteoprotegerin, whereas
      25(OH)D levels were decreased compared to controls. Increased PTH is positively
      correlated with NTpro- BNP (r=0.399, p<0.0001), adiponectin (r=0.398, p<0.0001),
      and osteoprotegerin, whereas negatively with 25(OH)D in CHF patients.
      Additionally, increased serum PTH was associated with endothelial dysfunction,
      echocardiographic variables of heart failure progression, impaired physical
      performance, and deteriorated quality of life. In a multivariate linear
      regression analysis, increased serum PTH was independently associated with
      neuroendocrine activation (NT-pro-BNP, adiponectin) and endothelial dysfunction
      in elderly CHF men (R2=0.455). Additionally, demonstrated relations with other
      well-established variables of heart failure severity suggest the potential role
      of serum PTH in the pathogenesis and non-invasive monitoring of heart failure
      progression. Future studies are needed to evaluate the predictive value of serum
      PTH for clinical outcomes as well as beneficial potential of PTH suppression in
      CHF patients.

PMID- 20820132
TI  - Effects of substitutive therapy on right ventricular systolic and diastolic
      functions in patients with idiopathic hypogonadotropic hypogonadism.
AB  - BACKGROUND: There have been controversial studies evaluating ventricular
      functions in patients with idiopathic hypogonadotropic hypogonadism (IHH). A
      recent study has demonstrated that low serum testosterone levels are associated
      with increased cardiovascular mortality. AIM: We aimed to investigate ventricular
      functions by standard echocardiography and examine the effects of substitutive
      therapy on right ventricular (RV) functions in patients with IHH by means of
      pulsed wave tissue Doppler imaging (PWTDI). METHODS: Twenty-three patients with
      IHH and 31 controls were evaluated by standard echocardiography and PWTDI.
      Isovolumic acceleration (IVA), myocardial systolic wave (Sm) velocity, myocardial
      precontraction time (PCTm), and PCTm to contraction time (CTm) ratio were
      determined as systolic indices. Myocardial relaxation time (RTm), early (Em)
      velocity, late (Am) velocity, and Em to Am ratio were determined as diastolic
      indices. RESULTS: Peak pulmonary artery pressure (PAP) was significantly higher
      in control subjects (p=0.008). IVA and Sm values were similar in patients and
      controls. Em, Am velocities, and their ratios did not differ. PCTm was
      significantly longer (p=0.001) and PCTm to CTm ratio was significantly higher in
      patients (p=0.001). These parameters also decreased after replacement therapy,
      albeit not statistically significantly (p>0.05). PAP was significantly higher
      after substitutive therapy (p=0.009). CONCLUSIONS: Ventricular functions are
      normal in patients with IHH. Substitutive therapy has no effects on RV functions.
      However, substitutive therapy may increase PAP in small amounts, which has no
      immediate clinical implication with short-term use.

PMID- 20820135
TI  - [Molecular biology in clinical allergology; what we have learned from
      eosinophils].

PMID- 20820136
TI  - [The relationship between inspiratory pressure and flow through dry powder
      inhaler available in Japan].
AB  - OBJECTIVE: Recently many of the inhaled drugs are provided as dry powder formula
      and prescribed for such diseases as COPD and asthma exacerbation. Inspiratory
      flow rate through the dry powder device (DPI) has a significant influence on
      therapeutic response in these disease conditions. We planned to measure flow vs.
      pressure relationships of almost all of the DPIs available in Japan. METHODS:
      Driving pressure (PI) and flow through the DPI were measured and the linear
      regression lines between PI and flow(2) were drawn. RESULTS: The slope and
      intercept of the regression lines were as follows: Turbuhaler for Pulmicort 79.26
      (l/s)(2)/cmH2O, 626 (l/s)(2), Turbuhaler for Symbicort 88.99, 688, Twisthaler
      56.37, 478, Diskus 125.98, 872, Diskhaler, 166.98, 780, Handihaler, 54.88, 498,
      Clickhaler, 78.37, 452. We drew P(I) vs flow curves of each DPIs for instruction
      of DPI devices to the patients. CONCLUSION: Inspiratory pressure is an excellent
      parameter to indicate optimal flow through DPI. Early escalation of medication
      may be important in the patients using Turbuhaler or Twisthaler that has higher
      resistance in inspiratory channel.

PMID- 20820137
TI  - [Differences in fraction of exhaled nitric oxide values measured by two offline
      methods or NIOXmino in adult Japanese asthmatics].
AB  - BACKGROUND: The fraction of exhaled nitric oxide (FeNO) is a useful marker of
      asthma control. The FeNO measurement with two offline methods and NIOXmino may be
      more affordable, no studies have examined the differences in FeNO values measured
      with various methods in adult asthmatics. METHODS: The study population comprised
      39 stable asthmatics treated with inhaled steroids at our outpatient clinic. FeNO
      values were measured by two offline methods (Sievers and CEIS), NIOXmino.
      RESULTS: FeNO(NIOXmino) values were significantly correlated with those of
      FeNO(Sievers) (r=0.935, P< 0.001) and FeNOCEIS (r=0.908, P< 0.001). However,
      FeNO(NIOXmino) values were low compared with FeNO(Sievers) (FeNO(NIOXmino)=0.848
      x FeNO(Sievers)) and FeNO(CEIS) (FeNO(NIOXmino)=0.672 x FeNO(CEIS)). CONCLUSION:
      Differences exist in the values of FeNO measured by various methods: conversion
      equations are needed to compare the FeNO values among these three methods.

PMID- 20820138
TI  - [Therapeutic effect of omalizumab on 10 patients with severe persistent asthma].
AB  - BACKGROUND: Therapeutic effect of omalizumab was studied in Japanese patients
      with severe asthma. METHODS: Omalizumab was administered to 10 patients with
      bronchial asthma diagnosed as severe or very severe persistent asthma according
      to Asthma Prevention Management Guideline 2009, Japan (JGL 2009). Therapeutic
      efficacy was assessed 16 weeks after starting the treatment using Asthma Control
      Test (ACT), pulmonary function tests, and the peripheral eosinophil counts. In
      addition, number of acute exacerbation in 16-week period after starting the
      treatment was compared with that in 16-week period before the treatment and the
      previous year respectively. The questionnaire whether or not to continue
      omalizumab was conducted 16 weeks after starting the treatment. RESULTS: The
      total ACT score rose from 14.8 to 19.1 and peripheral eosinophil count decreased
      from 355.2 /microl to 209.8 /microl after starting the treatment. Peak expiratory
      flow and forced expiratory volume in one second also increased, though
      differences were insignificant. Number of acute exacerbation decreased from 3.0
      times before the treatment and 2.4 times the same time last year to 1.3 times
      after starting the treatment. The result of the questionnaire revealed that
      patients wanted to discontinue because of financial burden, ambulant burden, and
      side effect, but no one responded to be ineffective. In fact, only the one
      discontinued omalizumab. CONCLUSION: Omalizumab produced improvement in subject
      symptoms and reduced acute exacerbation in patients with severe or very severe
      persistent asthma. The future challenge is to reduce financial and ambulant
      burden on patients.

PMID- 20820139
TI  - [Effect of osmolality on ion transport in Guinea pig airway epithelial cells].
AB  - BACKGROUND: Increased osmolality of the airway surface fluid due to water loss
      associated with hyperventilation is considered to be a cause of exercise-induced
      asthma (EIA). AIM: We investigated the influence of changes in osmolality on
      airway epithelial ion transport in guinea pigs. METHODS: We explored from
      measuring open circuit potential difference in challenge with hypertonic saline
      or mannitol. RESULTS: Diphenylamine-2-carboxylate (DPC), amiloride, and disodium
      cromoglycate (DSCG) prevented an increase of the potential difference (PD) after
      exposure of tracheal mucosa to 0.9-10.8% hypertonic saline solutions (HSSs) (p <
      0.05, p < 0.01, and p < 0.01, respectively on 1.8%). An increase of the PD was
      observed after a single dose of 1.8% hypertonic saline solution (HSS) was applied
      to the mucosa, but no increase was observed after a single exposure to a 585
      mOsm/kg aqueous mannitol solution (585AMS). The results remained the same when a
      Cl-free solution was used as the perfusate. The change of airway epithelial cell
      thickness was only suppressed significantly by DPC (p < 0.01) after 1.8% HSS
      challenge. CONCLUSIONS: Not only the change of osmolality, but also changes of
      the Cl- and Na+ concentrations in airway surface fluid seem to have an important
      influence on the PD. cAMP-dependent Cl- channel may have a role, and the same
      mechanism may provoke EIA.

PMID- 20820140
TI  - [My thoughts and memories: from prostaglandins to transcription factor].

PMID- 20820141
TI  - Best strategy to recruit primary ARDS: what to look for.

PMID- 20820142
TI  - Teaching fiberoptic intubation in Italy: state of the art.

PMID- 20820143
TI  - How to evaluate regional myocardial function during anesthesia? Measuring the
      strain rate is possible although difficult.

PMID- 20820144
TI  - Experienced hands would reduce failures of spinal anesthesia.

PMID- 20820145
TI  - Treatment of pain on injection with propofol: not a trivial matter!

PMID- 20820146
TI  - Different patterns of lung recruitment maneuvers in primary acute respiratory
      distress syndrome: effects on oxygenation and central hemodynamics.
AB  - BACKGROUND: The aim of this study was to test if different recruitment maneuver
      (RM) patterns, that achieve the same maximum pressure for the same length of time
      in humans, have a similar efficacy on alveolar recruitment, intrathoracic
      vascular pressures and flows, and on cardiac function and ventricular filling.
      METHODS: Forty patients were randomly allocated to undergo different RM patterns:
      sustained inflation (SI) or pressure controlled ventilation (PCV). The RM methods
      tested are as follows: SI was achieved by raising peak inspiratory pressure to 45
      cmH(2)O and sustaining it for 40 seconds. The PCV was set to obtain a 45 cmH(2)O
      peak inspiratory pressure for 2 minutes, I:E 1:2, PEEP 16 RR 8/min. During the
      study period, patients were mechanically ventilated to obtain a volume of 6
      mL/kg, FiO(2) 0.7, PEEP 14, RR 14, Pplateau < or =30 cmH(2)O according to the
      ARDSnet trial. All patients were sedated and paralyzed during the study period.
      All patients were given i.v. norepinephrine. Heart rate, pulse oxymetry, blood
      pressure, pulmonary artery catheter data (C.I., PVRI, MPAP, PAOP, SvO(2), CVP),
      and arterial and right heart side venous blood gas analysis data (ph, PaO(2),
      PaCO(2), SatO(2), HCO(3)(-), SvO(2)) were recorded before and immediately after
      the lung recruitment maneuver. The static compliance of the respiratory system
      (CRS) was recorded. Echocardiographic spot evaluations before and after RM were
      obtained in all cases. RESULTS: Central venous pressure increased during RM. Mean
      pulmonary artery pressure, pulmonary capillary wedge pressure and pulmonary
      vascular resistance index were reduced during PCV RM compared to SI RM (P<0.05).
      The right ventricle stroke work index decreased to a major extent during PCV RM
      (P<0.05). The P/F ratio was significantly increased after PCV RM compared to SI
      RM (P<0.05). PaCO(2) levels were similar in the two groups. Compared to baseline,
      the Qs/Qt decreased significantly after the PCV recruitment maneuver. Ventricular
      end-diastolic and end-systolic areas decreased during both RM protocols, but they
      were decreased to a greater extent after SI RM than after PCV RM (P<0.05). The
      eccentricity index increased from baseline after the SI RM (P<0.05). CONCLUSION:
      Given its comparable, or even superior, performance over the SI RM, we favor the
      PCV technique over the time-honored SI maneuver.

PMID- 20820147
TI  - A structured training program for awake fiber optic intubation: teaching the
      complete package.
AB  - BACKGROUND: We organized a training program for oral fiber optic intubation (FOI)
      under conscious sedation. The efficacy of the program was evaluated by comparing
      the performances of experts and novices. METHODS: The training procedure was
      divided into two sessions: a theoretical session on difficult airways, the fiber
      optic bronchoscope (FOB), remifentanil, topical anesthesia and patient
      interactions; and a session involving simulations of the FOI technique on
      dummies. For in vivo FOI, we enrolled patients requiring orotracheal intubation
      for elective surgery. Electrocardiograms, mean arterial pressure (MAP) values,
      peripheral O(2) saturation (SpO(2)) values, respiratory rates (RR) and sedation
      scores (OAA/S) were acquired. Remifentanil infusion was started at 0.05-0.1
      microg*kg(-1)*min(-1), and patients' upper airways were anesthetized with
      lidocaine. Remifentanil was titrated to achieve an OAA/S of 9-12. FOBs were
      inserted, and topical laryngeal anesthesia was achieved ("spray as you go"
      technique). The instrument was passed into the trachea, the OT tube was
      railroaded over the fiberscope, and tracheal intubation was completed. The
      procedure duration and patients' vital parameters and satisfaction were recorded.
      RESULTS: Three experts and four less-experienced anesthesiologists who performed
      29 (10, 10 and 9) and 25 (6, 6, 6 and 7) FOIs, respectively, joined the study. To
      reach the target OAA/S, the remifentanil dosage was progressively increased to an
      average dose of 0.15+/-0.05 microg*Kg(-1)*min(-1). MAP and SpO(2) values were
      stable throughout the procedures, HR was slightly increased (from 77+/-16 to 90+/
      23 bpm, P=0.02), and RR was decreased (from 16+/-3 to 12+/-4 bpm, P<0.05). No
      differences were recorded between the experts and less-experienced
      anesthesiologists. The average duration of FOI was 3.3+/-2.0 min for experts and
      4.2+/-2.4 min for novices (P=0.03). Procedures were successful in both groups,
      with patients in each group being equally satisfied with the procedures.
      CONCLUSION: This study highlights the importance of a structured FOI training
      program, demonstrating that it is possible to learn to perform FOI proficiently
      by practicing on dummies.

PMID- 20820148
TI  - Effects of fenoldopam on myocardial function (strain rate) in patients with
      coronary artery disease undergoing cardiac surgery.
AB  - BACKGROUND: This study aimed to assess the effects of fenoldopam, an
      antihypertensive agent with nephroprotective properties, on myocardial function.
      The global systolic and diastolic function and the strain rate, a new parameter
      used to quantify regional myocardial function, were measured with transesophageal
      echocardiography. METHODS: Forty patients undergoing elective coronary artery
      surgery were analyzed in a prospective nonrandomized clinical trial. Patients
      were divided into two groups, a group that received 0.05-mcg/kg/min fenoldopam
      (20 patients) and a control group (20 patients). Only patients with serum
      creatinine levels > or =120 micromol/L and critical coronary stenosis were
      selected. The ejection fraction (EF), the E and A waves, and the E/A ratio were
      measured with transesophageal echocardiography, and the strain rate was
      calculated using a strain quantification program to measure the peak systolic
      strain rate (PSSR) and the peak diastolic strain rate (PDSR). RESULTS: Fenoldopam
      did not change the systolic and diastolic global function (EF, E wave, A wave and
      E/A). Regarding regional myocardial function, fenoldopam significantly increased
      the PSSR from -1.09+/-0.8 1/s to -2.24+/-2.26 1/s (P=0.038) and the PDSR from
      1.04+/-0.69 1/s to 1.69+/-0.87 1/s (P=0.012). CONCLUSION: Low doses of fenoldopam
      increased the regional myocardial function, as assessed by the myocardial strain
      rate, in patients undergoing cardiac surgery.

PMID- 20820149
TI  - Conversion of spinal anesthesia into general anesthesia: an evaluation of more
      than 35,000 spinal anesthetics.
AB  - BACKGROUND: The aim of this study was to evaluate the number of conversions from
      spinal anesthesia (SA) into general anesthesia (GA) in a large number of patients
      who underwent surgery over a period of twenty-one years. METHODS: From the
      hospital's database, all surgical procedures performed under SA between January
      1, 1988 and December 31, 2008 were retrieved. From this file, all SA cases
      converted into GA cases requiring endotracheal intubation were selected. Patients
      were divided in four groups, according to the reason for GA: IMPOSS (SA
      impossible to perform), FAIL (SA non profound enough for allowing surgery, even
      with light sedation), INSUFF (SA inadequate for unexpected prolonged duration of
      surgery), and COMPL (occurrence of complications associated with SA and requiring
      rapid control of ventilation). Anesthesiologists who performed SA were divided
      according their experience. The outcomes of patients converted to GA were
      compared with a matched sample of patients who received planned GA. RESULTS: A
      total of 35,960 SA cases were performed from 1988 to 2008; 29,220 and 6,740 SA
      cases were for elective and emergency surgery, respectively. Two hundred
      seventeen (0.6%) SA cases were converted into GA cases; 80.2% and 19.8% of the
      conversions were recorded in elective and emergency operations, respectively,
      with obstetric operations being the most prevalent (82/217). The primary reasons
      for the conversions, in a rank order, were INSUFF 107 (49.3%), FAIL 84 (38.7%),
      IMPOSS 13 (5.9%), and COMPL 13 (5.9%). Complications more frequently occurred in
      the aged population (P<0.05). Anesthesiologists with less experience had higher
      percentages of FAIL, IMPOSS, INSUFF, and COMPL SA cases in comparison with
      experienced anesthesiologists (odd ratios being 4.7, 3.0, 2.4, and 4.4,
      respectively). There was no difference in the frequency of complications compared
      to a matched sample of 1,000 patients who underwent GA (P=0.65). CONCLUSION: SA
      has been found to be a safe and highly effective technique. Failure of SA was
      infrequent in a large number of patients surveyed and most often occurred with
      less experienced anesthesiologists. Conversion to GA did not produced different
      outcomes in comparison with planned GA. Prospective studies with a definite
      protocol for recording data performed on a large number of patients may help in
      determining the factors associated with conversion from SA into GA and how to
      avoid these unexpected situations.

PMID- 20820150
TI  - Propofol injection pain: is it still an issue? The effect of premedication.
AB  - BACKGROUND: The use of propofol often results in pain upon injection. Various
      strategies can be used to reduce this pain, ranging from the administration of
      analgesics to modification of the propofol emulsion. However, basic premedication
      protocol aimed at peri- and postoperative pain reduction could also sufficiently
      reduce propofol injection pain, rendering other special interventions redundant.
      METHODS: With the approval of the Local Ethics Committee of the Erasmus Medical
      Centre Rotterdam, and after obtaining written informed consent from each patient
      included, 209 surgical patients (ASA physical status I-III) were randomized in a
      double-blind manner to receive premedication consisting of 7.5 mg midazolam, 50
      mg diclofenac and 1000 mg acetaminophen (all orally administered) and fentanyl
      (intravenously administered) or placebo medication the hour before surgery. In
      both groups a mixture of 40 mL propofol 1% with 2 mL lidocaine 1% was used to
      induce anesthesia. Pain scores were assessed using a verbal analog scale (VAS)
      ranging from 0-10. RESULTS: The premedication group was found to have
      significantly less pain upon injection of propofol (median VAS 0+/-0-2) (median+/
      interquartile range) when compared to the control group (median VAS 1.5+/-0-4;
      P=0.001). In addition, more patients in the premedication group experienced no
      pain at all. This effect was still present one hour after extubation. CONCLUSION:
      Even when injection pain is reduced, the use of a premedication regimen clearly
      has additional value with respect to the patients' experience. Considering the
      low VAS scores observed overall, it might be worthwhile to reserve additional
      injection pain-reducing interventions for individual patients rather than adding
      them as a component of standard practice.

PMID- 20820151
TI  - Chronic kidney disease: implications for the perioperative period.
AB  - End-stage renal disease (ESRD) and chronic kidney disease (CKD) are increasing
      health problems worldwide. In the US alone, an estimated 26 million people suffer
      from some form of CKD. In countries such as India and Pakistan, the prevalence of
      CKD is also rapidly rising. The presence of CKD is associated with increased
      perioperative morbidity and mortality, even when adjusted for other variables
      such as hypertension or diabetes. Frequently, CKD is under diagnosed, so patients
      and physicians are often unaware of the impaired renal function. Renal
      dysfunction as a predictor of perioperative outcomes is discussed together with
      therapeutic interventions aimed at the protection of renal function. Better
      interventions and diagnostic tools, such as cystatin C, are needed to further
      improve perioperative morbidity and mortality in patients with CKD.

PMID- 20820152
TI  - Is monocyte HLA-DR expression monitoring a useful tool to predict the risk of
      secondary infection?
AB  - Downregulation of the immune response is common among Intensive Care Unit (ICU)
      patients after an acute inflammatory injury, whether it was septic or not. Such a
      modification could be seen as an adaptation to attenuate the effects of the
      inflammatory storm on tissues, but it exposes the subject to the risk of
      nosocomial infection and impairs recovery processes. The intensity of immunity
      downregulation is difficult to characterize, since clinical presentation is
      silent and non-specific, which urges the use of tools for immune monitoring. This
      review focuses on the use of monocyte HLA-DR expression to detect immune
      hyporesponsiveness and to select the appropriate immunomodulating therapy, as
      well as the efficiency of this technique in controlling secondary infections.

PMID- 20820153
TI  - The elderly and general anesthesia.
AB  - Due to the aging population, the number of elderly patients taking advantage of
      healthcare services is increasing. A general physical decline of all organ
      systems and a high frequency of chronic disease accompanying aging.Comorbidity
      and polypharmacy are therefore common in the elderly. Hence, the administration
      of general anesthesia to the elderly can be a very challenging task. This paper
      aims to highlight some of the important issues presented to the elderly
      undergoing surgery and to suggest some strategies for management.

PMID- 20820154
TI  - Patient safety in anesthesia.
AB  - Medical mistakes have been identified as resulting from a breakdown in one or
      more of five major areas: equipment performance, communication, staffing levels,
      complex environments and workloads. Because many of these areas relate directly
      to the practice of anesthesiology, they can contribute significantly to the
      safety and quality of the use of anesthesia. The specialty of anesthesia has
      embraced a culture of safety, resulting in many beneficial improvements for
      patients. The avoidance of error has led to improved outcomes, with a decrease in
      directly attributable rates of morbidity and mortality. Despite these improved
      rates, there are still areas that can be improved. This paper describes the
      background of these issues, discusses areas where performance has improved and
      identifies the areas in which there is room for further improvement.

PMID- 20820155
TI  - Leprosy: a precipitating factor for complex regional pain syndrome.
AB  - Complex regional pain syndrome (CRPS) usually develops after trauma. We are
      reporting the first case of CRPS with leprosy as a precipitating cause. A fifty
      five-year male presented in the pain clinic with complaint of pain and swelling
      in the right arm. There was no history of trauma to the limb. On reviewing the
      history, patient was found to be on treatment for leprosy. X-ray of the right
      hand showed severe osteoporosis. A diagnosis of CRPS associated with leprosy was
      made. A diagnostic stellate ganglion block relived his pain completely.
      Thereafter patient is on treatment with tablet etoricoxib 90 mg once a day,
      gabapentin 100 mg twice a day and continuing to have 100% pain relief. The
      diagnosis of the type of CRPS was difficult in our case as no history of trauma
      or neurological injury was present. The presence of leprosy along with ulnar
      nerve thickening may be the precipitating factor for CRPS, this has not been
      reported so far in the literature. We managed the patient with sympathetic block
      along with medical therapy for chronic pain and leprosy chemotherapy.

PMID- 20820156
TI  - Management of a patient with an unexpected obstructing carinal mass.
AB  - Surgical procedures involving the airway or for mediastinal masses present
      considerable challenges for the anesthesiologist. Aside from the obvious
      technical challenges of providing ventilation, the anesthesiologist must share
      the airway with the surgeon. Careful and meticulous preoperative evaluation and
      preparation and intraoperative interaction with the surgical team is critical to
      assure control of the airway. We report a case of management of a patient with an
      unexpected near total obstruction of the airway from a carinal mass.

PMID- 20820157
TI  - Anesthetic management of massive life-threatening hemoptysis.

PMID- 20820158
TI  - Oral to nasal tracheal tube change.

PMID- 20820160
TI  - The First International Conference on Translational Medicine.

PMID- 20820161
TI  - Exposure science can increase protection of workers and their families from
      exposure to asbestos and inform on the effects of other elongate mineral
      particles.

PMID- 20820162
TI  - Vehicle emissions: progress and challenges.

PMID- 20820163
TI  - Response to the comment by Henry Kahn and Dennis Santella on a summary of the
      development of a signature for detection of residual dust from the collapse of
      the World Trade Center buildings.

PMID- 20820167
TI  - The APOE E4 allele modulates brain white matter integrity in healthy adults.
AB  - The Apolipoprotein E (APOE) E4 allele is the best-established genetic risk factor
      for sporadic Alzheimer's disease, and is also associated with structural gray
      matter and functional brain changes in healthy young, middle-aged and elderly
      subjects. Because APOE is implicated in brain mechanisms associated with white
      matter (WM) development and repair, we investigated the potential role played by
      the APOE polymorphism on WM structure in healthy younger (aged 20-35 years) and
      older (aged 50-78 years) adults using diffusion tensor imaging. General reduction
      of fractional anisotropy and increase in mean diffusivity values was found in
      carriers of the APOE E4 allele relative to non-carriers. No significant
      interactions between genotype and age were observed, suggesting that differences
      in WM structure between APOE E4-carriers and non-carriers do not undergo
      significant differential changes with age. This result was not explained by
      differences in brain morphology or cognitive measures. The APOE E4 allele
      modulates brain WM structure before any clinical or neurophysiological expression
      of impending disease.

PMID- 20820169
TI  - Medical student bias and care recommendations for an obese versus non-obese
      virtual patient.
AB  - OBJECTIVE: This study examined the independent effect of a patient's weight on
      medical students' attitudes, beliefs and interpersonal behavior toward the
      patient, in addition to the clinical recommendations they make for her care.
      DESIGN: A total of 76 clinical-level medical students were randomly assigned to
      interact with a digital, virtual female patient who was visibly either obese or
      non-obese. METHODS: Interactions with the patient took place in an immersive
      virtual (virtual reality) clinical environment that allowed standardization of
      all patient behaviors and characteristics except for weight. Visual contact
      behavior was automatically recorded during the interaction. Afterward,
      participants filled out a battery of self-report questionnaires. RESULTS:
      Analyses revealed more negative stereotyping, less anticipated patient adherence,
      worse perceived health, more responsibility attributed for potentially weight
      related presenting complaints and less visual contact directed toward the obese
      version of a virtual patient than the non-obese version of the patient. In
      contrast, there was no clear evidence of bias in clinical recommendations made
      for the patient's care. CONCLUSION: Biases in attitudes, beliefs and
      interpersonal behavior have important implications because they can influence the
      tone of clinical encounters and rapport in the patient-provider relationship,
      which can have important downstream consequences. Gaining a clear understanding
      of the nature and source of weight bias in the clinical encounter is an important
      first step toward the development of strategies to address it.

PMID- 20820170
TI  - Inverse associations between long-term weight change and serum concentrations of
      persistent organic pollutants.
AB  - There is emerging evidence that persistent organic pollutants (POPs) can increase
      the risk of various chronic diseases. As POPs mainly bioaccumulate in adipose
      tissue, weight change can affect serum concentrations of POPs. However, there are
      few population-based studies on effects of long-term weight change on serum
      concentrations of POPs. We examined associations between self-reported weight
      change over 1 year and 10 years and serum concentrations of seven POPs in 1099
      adults aged >= 40. Serum concentrations of most POPs were higher in those with
      long-term weight loss, whereas they were lower in those with long-term weight
      gain. Adjusted correlation coefficients of each POP with weight change for 10
      years were -0.23 (P < 0.01) for trans-nonachlor, -0.16 (P < 0.01) for p,p'
      dichlorodiphenyldichloroethylene, and -0.21 (P < 0.01) for beta
      hexachlorocyclohexane, -0.16 (P < 0.01) for PCB169, -0.20 (P < 0.01) for PCB180
      and -0.17 (P < 0.01) for 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin. Weight change
      for 1 year showed similar but weaker associations, compared with those of long
      term weight changes. Although both beneficial health effects after weight loss
      and harmful health effects after weight gain are generally expected, changes in
      serum concentrations of POPs in relation to weight change may act on health in
      directions opposite to what we expect with weight change.

PMID- 20820171
TI  - Potato protease inhibitors inhibit food intake and increase circulating
      cholecystokinin levels by a trypsin-dependent mechanism.
AB  - OBJECTIVE: To investigate the mechanisms underlying the satiety-promoting effects
      of a novel protease inhibitor concentrate derived from potato (PPIC). METHODS:
      The acute and prolonged effects of oral PPIC administration (100 mg kg(-1) per
      day) on food intake, body weight and gastric emptying were evaluated in healthy
      rats. Parameters of body weight, food intake, plasma glucose, insulin and
      cholecystokinin (CCK) were measured. Duodenal proteolytic activity and CCK
      expression were determined in tissue extracts. Intestinal STC-1 cell culture
      model was used to investigate the direct effect of PPIC on CCK transcript level
      and secretion. RESULTS: Acute oral administration of PPIC reduced immediate food
      intake during the first 2 h following the treatment, delayed gastric emptying and
      decreased proteolytic activity in the duodenum. Repeated oral ingestion of PPIC
      reduced weight gain in male rats and significantly elevated the plasma CCK
      levels. Although duodenal mucosal CCK mRNA levels increased in response to PPIC
      administration, the concentrate failed to elevate CCK expression or release in
      STC-1 cells. The 14-day ascending dose range study (33-266 mg kg(-1) PPIC per
      day) showed no adverse side effects associated with PPIC administration.
      CONCLUSION: These findings provided evidence that PPIC is effective in reducing
      food intake and body weight gain in healthy rats when administered orally by
      increasing circulating CCK levels through a trypsin-dependent mechanism.

PMID- 20820173
TI  - Trends in obesity and abdominal obesity among adults in the United States from
      1999-2008.
AB  - BACKGROUND AND OBJECTIVE: The United States has experienced a large increase in
      the prevalence of obesity since the 1970s. Our objective was to describe recent
      trends in obesity and abdominal obesity among adults in the United States.
      DESIGN: Trend study of cross-sectional studies. SUBJECTS: We used data from up to
      22,872 men and non-pregnant women aged >= 20 years from the National Health and
      Nutrition Examination Survey (NHANES) 1999-2008. MAIN OUTCOME MEASURES: Main
      outcome measures are mean body mass index and waist circumference, percentages of
      obesity and abdominal obesity. Obesity was defined as a body mass index >= 30 kg
      m(-2), and abdominal obesity was defined as a waist circumference >= 102 cm in
      men and >= 88 cm in women. RESULTS: In men, the age-adjusted mean body mass
      index, mean waist circumference, and prevalence of obesity and abdominal obesity
      were 27.8 kg m(-2), 99.1 cm, and 26.9 and 37.8%, respectively, during 1999-2000
      and 28.5 kg m(-2) (P (trend) = 0.001), 100.8 cm (P (trend) = 0.002), and 32.0 (P
      (trend) = 0.001) and 43.7% (P (trend) = 0.002), respectively, during 2007-2008.
      In women, the age-adjusted mean body mass index, mean waist circumference, and
      prevalence of obesity and abdominal obesity were 28.2 kg m(-2), 92.2 cm, and 33.2
      and 55.8%, respectively, during 1999-2000 and 28.6 kg m(-2) (P (trend) = 0.181),
      94.9 cm (P (trend) = 0.006), and 35.2 (P (trend) = 0.180) and 61.8% (P (trend) =
      0.036), respectively, during 2007-2008. Significant linear trends for increasing
      prevalence of obesity were noted among men with the least and most education.
      CONCLUSION: Between 1999 and 2008, both obesity and abdominal obesity increased
      in men, and abdominal obesity increased in women.

PMID- 20820172
TI  - Adiposity changes after a 1-year aerobic exercise intervention among
      postmenopausal women: a randomized controlled trial.
AB  - OBJECTIVE: We examined the effects of an aerobic exercise intervention on
      adiposity outcomes that may be involved in the association between physical
      activity and breast cancer risk. DESIGN: This study was a two-centre, two-armed,
      randomized controlled trial. The 1-year-long exercise intervention included 45 
      min of moderate-to-vigorous aerobic exercise five times per week, with at least
      three of the sessions being facility based. The control group was asked not to
      change their activity and both groups were asked not to change their diet.
      SUBJECTS: A total of 320 postmenopausal, sedentary, normal weight-to-obese women
      aged 50-74 years who were cancer-free, nondiabetic and nonhormone replacement
      therapy users were included in this study. MEASUREMENTS: Anthropometric
      measurements of height, weight and waist and hip circumferences; dual energy X
      ray absorptiometry measurements of total body fat; and computerized tomography
      measurements of abdominal adiposity were carried out. RESULTS: Women in the
      exercise group exercised a mean of 3.6 days (s.d.=1.3) per week and 178.5  min
      (s.d.=76.1) per week. Changes in all measures of adiposity favored exercisers
      relative to controls (P<0.001). The mean difference between groups was: -1.8  kg
      for body weight; -2.0  kg for total body fat; -14.9  cm(2) for intra-abdominal
      fat area; and -24.1  cm(2) for subcutaneous abdominal fat area. A linear trend of
      greater body fat loss with increasing volume of exercise was also observed.
      CONCLUSION: A 1-year aerobic exercise program consistent with current public
      health guidelines resulted in reduced adiposity levels in previously sedentary
      postmenopausal women at higher risk of breast cancer.

PMID- 20820174
TI  - Weight-loss diet alone or combined with resistance training induces different
      regional visceral fat changes in obese women.
AB  - BACKGROUND: Quantification of abdominal fat and its regional distribution has
      become increasingly important in assessing the cardiovascular risk. OBJECTIVE: To
      examine the effects of 16 weeks of a hypocaloric diet with a caloric restriction
      of 500 Kcal per day (WL) or the same dietary intervention plus resistance
      training (WL+RT) on regional variation of abdominal visceral (visceral adipose
      tissue (VAT)) and subcutaneous (subcutaneous adipose tissue (SAT)) fat loss.
      Second, to identify the single-image that best represents total magnetic
      resonance imaging measurements of total VAT and SAT volume before and after WL or
      WL+RT intervention. DESIGN: A total of 34 obese (body mass index: 30-40 kg m(-2))
      women, aged 40-60 years, were randomized to three groups: a control group (C; n =
      9), a diet group (WL; n = 12) and a diet plus resistance training group (WL+RT; n
      = 13) with the same caloric restriction as group WL and a 16-week supervised
      whole-body RT of two sessions per week. RESULTS: WL+RT programs lead to
      significant changes in the location of highest mean VAT area from L3-L4 to L2-L3
      discal level from pre- to post- intervention, whereas after WL the greatest
      relative VAT losses were located at L5-S1. Similar decreases in the SAT areas at
      all discal levels were observed after WL and WL+RT. CONCLUSION: Different weight
      loss regimes may lead to different distribution of VAT. Sites located
      significantly above (cranial to) L4-L5 (that is, ~ 5-6 cm above L4-L5 or at L2-L3
      discal level) provided superior prediction of total abdominal VAT volume, whereas
      more caudal slices provide better prediction of subcutaneous fat, not only before
      but also after either WL or WL+RT.

PMID- 20820175
TI  - Framing messages about weight discrimination: impact on public support for
      legislation.
AB  - OBJECTIVE: To assess the public support for potential legislation to prohibit
      weight-based discrimination against obese individuals in the United States, and
      to examine whether certain message frames about weight discrimination influence
      public support. DESIGN: Participants were randomly assigned to read one of the
      four paragraphs that framed the topic of weight discrimination in a distinct way
      (or a control condition with no paragraph). Participants were then asked to
      indicate their level of support for six antidiscrimination laws. SUBJECTS: A
      national sample of 1114 participants (48% women, 52% men), mean age 44.78 years
      (s.d. = 15.93). RESULTS: There was moderate support for several laws to prohibit
      weight-based discrimination, but gender differences were observed across
      experimental conditions indicating that some message frames may increase support
      for certain laws among women, but not men. However, message frames had no effect
      on support for laws with specific provisions to prohibit weight discrimination in
      the workplace, suggesting that public support for these particular legal measures
      is consistent and high (65% of men and 81% of women expressed support) regardless
      of how the issue of weight discrimination is framed to the public. CONCLUSION:
      The present findings provide evidence of current levels of public support for
      legislation to prohibit weight-based discrimination, and offer potential ways for
      policy makers and interest groups to communicate messages about weight
      discrimination in efforts to increase support.

PMID- 20820176
TI  - Oxycodone improves pain control and quality of life in anticonvulsant-pretreated
      spinal cord-injured patients with neuropathic pain.
AB  - STUDY DESIGN: A 3-month follow-up, observational, prospective, multicenter, study
      in traumatic spinal cord-injured (SCI) patients with neuropathic pain (NP).
      OBJECTIVES: To assess the effectiveness and safety of oxycodone treatment in SCI
      patients with anticonvulsants-refractory NP. SETTING: 'Spinal injury follow-up
      units' throughout Spain. METHODS: Data regarding NP characteristics were collated
      from male and female adults with traumatic SCI and difficult-to-control central
      NP of moderate-to-severe intensity (visual analog scale (VAS) >=4) persisting >=1
      month, who had been para- or tetraplegic for >=2 months, had been previously
      treated with anticonvulsants and were now treated with oxycodone. RESULTS: In
      all, 54 out of the 57 patients recruited were assessable. A total of 81% were men
      and the mean age was 46.4. Patients were treated with oxycodone, 83% combined
      with anticonvulsant. Pain intensity (VAS: 7.1 +/- 1.3-4.3 +/- 1.7) and Lattinen
      total score (13.2 +/- 3-7.7 +/- 3.4) decreased significantly (P < 0.001) along
      the study. No patient got worse regarding pain impact on physical activity and on
      sleep (Lattinen scale). EQ-5D VAS showed a trend to increase (P = 0.061) and the
      index of preference values increased significantly from baseline to month 3 (0.26
      0.62; P < 0.001). A total of 53.7% patients showed at least one treatment-related
      adverse event, with constipation being the most frequent one (33.3%). CONCLUSION:
      Oxycodone treatment, mostly in combination with anticonvulsants, in SCI patients
      with NP decreases pain intensity, improves health-related quality of life and
      diminishes the impact of pain on physical activity and sleep.

PMID- 20820177
TI  - Plasma iron levels appraised 15 days after spinal cord injury in a limb movement
      animal model.
AB  - STUDY DESIGN: Experimental, controlled trial. OBJECTIVES: The purpose of this
      study was to evaluate plasma iron and transferrin levels in a limb movement
      animal model with spinal cord injury (SCI). SETTING: Universidade Federal de Sao
      Paulo, Departamento de Psicobiologia. METHODS: In all, 72 male Wistar rats aged
      90 days were divided into four groups: (1) acute SCI (1 day, SCI1), (2) 3 days
      post-SCI (SCI3), (3) 7 days post-SCI (SCI7) and (4) 15 days post-SCI (SCI15).
      Each of these groups had corresponding control (CTRL) and SHAM groups. Plasma
      iron and transferrin levels of the different groups were analyzed using a one-way
      analysis of variance (ANOVA) followed by Tukey's test. RESULTS: We found a
      significant reduction in iron plasma levels after SCI compared with the CTRL
      group: SCI1 (CTRL: 175+/-10.58 MUg dl(-1); SCI: 108.28+/-11.7 MUg dl(-1)), SCI3
      (CTRL: 195.5+/-11.00 MUg dl(-1); SCI: 127.88+/-12.63 MUg dl(-1)), SCI7 (CTRL:
      186+/-2.97 MUg dl(-1); SCI: 89.2+/-15.39 MUg dl(-1)) and SCI15 (CTRL: 163+/-5.48
      MUg dl(-1); SCI: 124.44+/-10.30 MUg dl(-1)) (P<0.05; ANOVA). The SHAM1 group
      demonstrated a reduction in iron plasma after acute SCI (CTRL: 175+/-10.58 MUg
      dl(-1); SHAM: 114.60+/-7.81 MUg dl(-1)) (P<0.05; ANOVA). CONCLUSION: Reduced iron
      metabolism after SCI may be one of the mechanisms involved in the pathogenesis of
      sleep-related movement disorders.

PMID- 20820178
TI  - SCIM III is reliable and valid in a separate analysis for traumatic spinal cord
      lesions.
AB  - STUDY DESIGN: A multi-center international cohort study. OBJECTIVE: To evaluate
      the reliability and validity of the third version of the Spinal Cord Independence
      Measure (SCIM III), separately for patients with traumatic spinal cord lesions
      (SCLs). SETTING: A total of 13 spinal cord units in six countries from North
      America, Europe and the Middle-East. METHODS: SCIM III and Functional
      Independence Measure (FIM) were assessed for 261 patients with traumatic SCLs, on
      admission to rehabilitation and before discharge, by two raters. Conventional
      statistical measures were used to evaluate the SCIM III reliability and validity.
      RESULTS: In almost all SCIM III tasks, the total agreement between the paired
      raters was >80%. The kappa coefficients were all >0.6 and statistically
      significant. Pearson's coefficients of the correlations between the paired raters
      were >0.9, the mean differences between raters were nonsignificant and the
      intraclass correlation coefficients (ICCs) were >= 0.95. Cronbach's alpha values
      for the entire SCIM III scale were 0.833-0.835. FIM and SCIM III total scores
      were correlated (r=0.84, P<0.001). SCIM III was more responsive to changes than
      FIM. In all subscales, SCIM III identified more changes in function than FIM, and
      in 3 of the 4 subscales, differences in responsiveness were statistically
      significant (P<0.02). CONCLUSION: The results confirm the reliability and
      validity of SCIM III for patients with traumatic SCLs in a number of countries.

PMID- 20820179
TI  - Is there a difference between narrowing of the spinal canal and neurological
      deficits comparing Denis and Magerl classifications?
AB  - STUDY DESIGN: Retrospective chart review. OBJECTIVES: The objective of the
      current study was to evaluate the correlation between neurological deficits and
      the severity of narrowing of the spinal canal in patients with thoracic,
      thoracolumbar and lumbar burst-type fractures by comparing the classifications of
      Denis and Magerl. From 1989 to 2005, a total of 227 patients with burst fractures
      following Denis' criteria were studied. SETTING: Tertiary teaching institution.
      METHODS: Computed tomographic scans of the fractured spine were analyzed to
      assess the narrowing of the spinal canal. Following Magerl's criteria, patients
      were later subdivided into two groups according to the presence of associated
      ligament injuries, out of which 185 patients had no such injuries and the
      remaining 42 patients were classified as Megerl group B. RESULTS: Results were
      evaluated based on the initial neurological status of patients according to
      Frankel and based on the midsagittal diameter of the fractured vertebra. A
      significant correlation was found between the narrowing of the spinal canal and
      neurological deficits in both classifications, with no significant differences
      between either. CONCLUSION: The percentage of narrowing of the spinal canal
      proved to be a pre-disposing factor for the severity of the neurological status
      in thoracolumbar and lumbar burst-type fractures according to the classifications
      of Denis and Magerl. The greater the bone fragment in the spinal canal, the
      greater will be the probability of neurological deficits in both fracture
      classifications, equally.

PMID- 20820180
TI  - How does knowledge about spinal cord injury-related complications develop in
      subjects with spinal cord injury? A descriptive analysis in 214 patients.
AB  - STUDY DESIGN: Monocentric cohort study. OBJECTIVE: To investigate the acquisition
      of knowledge about spinal cord injury (SCI)-related complications in SCI
      patients. SETTING: Level 1 trauma center. METHODS: All patients with a traumatic
      or non-traumatic SCI were included in the study. Data were collected at
      admission, post-admission at 1 and 3 months and post-discharge at 6, 18 and 30
      months. The discharge of all patients was between 3 and 6 months post-admission.
      Knowledge about pressure ulcers and bladder management was tested using the
      'Knowledge' score. This score has a minimum and maximum of 0 and 20 points. To
      detect differences across the multiple time intervals, the Friedman test was
      used. Differences in the number of patients with poor (0-8), average (9-12) and
      good knowledge (13-20) between the different age classifications (age at injury)
      were calculated using a chi (2)-test. RESULTS: A total of 214 patients were
      included. At discharge subjects had increased their knowledge score to 11.2
      compared with 5.4 on admission (P < 0.001). After 30 months, however, the mean
      score decreased to 10.8 points. At the time of discharge, the number of patients
      who achieved poor, average or good knowledge were 48 (22.4%), 65 (30.4%) and 101
      (47.2%), respectively. Subjects of ~50 years old and tetraplegics had better (P <
      0.001) knowledge compared with subjects of ~50 years old and paraplegics,
      respectively. CONCLUSION: In this study, less than 50% of SCI patients had good
      knowledge about bladder management and pressure ulcers after being discharged.

PMID- 20820181
TI  - Disease genetics: SNPs and the structural deficit.

PMID- 20820182
TI  - Regulatory elements: Predicting functional modules.

PMID- 20820183
TI  - Functional genomics: Vitamin D and disease.

PMID- 20820185
TI  - Stress hormones and AMPA receptor trafficking in synaptic plasticity and memory.
AB  - The acquisition and consolidation of memories of stressful events is modulated by
      glucocorticoids, a type of corticosteroid hormone that is released in high levels
      from the adrenal glands after exposure to a stressful event. These effects occur
      through activation of mineralocorticoid receptors (MRs) and glucocorticoid
      receptors (GRs). The molecular mechanisms that underlie the effects of
      glucocorticoids on synaptic transmission, synaptic plasticity, learning and
      memory have recently begun to be identified. Glucocorticoids regulate AMPA (alpha
      amino-3-hydroxyl-5-methyl-4-isoxazole-propionate) receptor trafficking--which is
      crucially involved in synaptic transmission and plasticity--both rapidly and
      persistently. Stress hormones may, through modulation of AMPA receptor function,
      promote the consolidation of behaviourally relevant information.

PMID- 20820186
TI  - Overexpression of C-MYC oncogene in prostate cancer predicts biochemical
      recurrence.
AB  - Alterations of chromosome 8, including amplification at 8q24 harboring the C-MYC
      oncogene, have been noted as one of the most common chromosomal abnormalities in
      prostate cancer (CaP) progression. However, the frequency of C-MYC alterations in
      CaP has remained uncertain. A recent study, using a new anti-MYC antibody,
      described prevalent upregulation of nuclear C-MYC protein expression as an early
      oncogenic alteration in CaP. Further, we have recently reported regulation of C
      MYC expression by ERG and a significant correlation between C-MYC overexpression
      and TMPRSS2-ERG fusion in early stage CaP. These emerging data suggest that
      increased C-MYC expression may be a critical and early oncogenic event driving
      CaP progression. In this study, we assessed whether C-MYC mRNA overexpression in
      primary prostate tumors was predictive of more aggressive tumor or disease
      progression. Our approach was to quantitatively determine C-MYC mRNA expression
      levels in laser capture micro-dissected tumor cells and matched benign epithelial
      cells in a radical prostatectomy cohort with long follow-up data available. On
      the basis of our results, we conclude that elevated C-MYC expression in primary
      prostate tumor is biologically relevant and may be a predictor of future
      biochemical recurrence.

PMID- 20820184
TI  - Ten years of genetics and genomics: what have we achieved and where are we
      heading?
AB  - To celebrate the first 10 years of Nature Reviews Genetics, we asked eight
      leading researchers for their views on the key developments in genetics and
      genomics in the past decade and the prospects for the future. Their responses
      highlight the incredible changes that the field has seen, from the explosion of
      genomic data and the many possibilities it has opened up to the ability to
      reprogramme adult cells to pluripotency. The way ahead looks similarly exciting
      as we address questions such as how cells function as systems and how complex
      interactions among genetics, epigenetics and the environment combine to shape
      phenotypes.

PMID- 20820187
TI  - miR-148a is an androgen-responsive microRNA that promotes LNCaP prostate cell
      growth by repressing its target CAND1 expression.
AB  - Recent advances in cancer biology reveal that microRNAs (miRNAs) are involved in
      the regulation of cancer-related genes, or they function as tumor suppressors or
      oncogenes. In prostate cancer, evidence has accumulated for the contribution of
      the androgen-dependent gene network to tumor growth, although the precise
      functions of miRNAs in prostate cancer remain to be investigated. Here, we
      identified androgen-responsive miRNAs by the short RNA sequencing analysis in
      LNCaP prostate cancer cells. Among 10 miRNAs with known sequences, we have
      determined that miR-148a reduces the expression of cullin-associated and
      neddylation-dissociated 1 (CAND1), a negative regulator of SKP1-Cullin1-F-box
      (SCF) ubiquitin ligases, by binding to the 3'-untranslated region of CAND1 mRNA.
      CAND1 knockdown by small interfering RNA promoted the proliferation of LNCaP
      cells. Our study indicates the potential contribution of miR-148a to the growth
      of human prostate cancer.

PMID- 20820188
TI  - Epithelial plasticity, stemness and pluripotency.

PMID- 20820189
TI  - FOXA2 functions as a suppressor of tumor metastasis by inhibition of epithelial
      to-mesenchymal transition in human lung cancers.
AB  - The forkhead box transcription factor A2 (FOXA2) is an important regulator in
      animal development and body homeostasis. However, whether FOXA2 is involved in
      transforming growth factor beta1 (TGF-beta1)-mediated epithelial-to-mesenchymal
      transition (EMT) and tumor metastasis remains unknown. The present study showed
      that in human lung cancer cell lines, the abundance of FOXA2 positively
      correlates with epithelial phenotypes and negatively correlates with the
      mesenchymal phenotypes of cells, and TGF-beta1 treatment decreased FOXA2 protein
      level. Consistently, knockdown of FOXA2 promoted EMT and invasion of lung cancer
      cells, whereas overexpression of FOXA2 reduced the invasion and suppressed TGF
      beta1-induced EMT. In addition, knockdown of FOXA2 induced slug expression, and
      ectopic expression of FOXA2 inhibited slug transcription. Furthermore, we
      identified that FOXA2 can bind to slug promoter through a conserved binding site,
      and that the DNA-binding region and transactivation region II of FOXA2 are
      required for repression of the slug promoter. These data demonstrate that FOXA2
      functions as a suppressor of tumor metastasis by inhibition of EMT.

PMID- 20820190
TI  - Not miR-ly aging: SIRT1 boosts memory via a microRNA-dependent mechanism.

PMID- 20820191
TI  - iPSC lines that do not silence the expression of the ectopic reprogramming
      factors may display enhanced propensity to genomic instability.
AB  - Here, we provide data suggesting that the absence of silencing of the ectopic
      reprogramming factors used to reprogram somatic cells to induced pluripotent stem
      cells (iPSCs) may predispose iPSCs to genomic instability. We encourage stem cell
      scientists to undertake an extensive characterization and standardization of much
      larger cohorts of iPSC lines in order to set up rigorous criteria to define safe
      and stable bona fide iPSCs.

PMID- 20820192
TI  - BRCA1 affects global DNA methylation through regulation of DNMT1.
AB  - Global DNA hypomethylation at CpG islands coupled with local hypermethylation is
      a hallmark for breast cancer, yet the mechanism underlying this change remains
      elusive. In this study, we showed that DNMT1, which encodes a methylation
      maintenance enzyme, is a transcriptional target of BRCA1. BRCA1 binds to the
      promoter of the DNMT1 gene through a potential OCT1 site and the binding is
      required for maintaining a transcriptional active configuration of the promoter
      in both mouse and human cells. We further demonstrated that impaired function of
      BRCA1 leads to global DNA hypomethylation, loss of genomic imprinting, and an
      open chromatin configuration in several types of tissues examined in a BRCA1
      mutant mouse model at premaligant stages. BRCA1 deficiency is also associated
      with significantly increased expression levels of several protooncogenes,
      including c-Fos, Ha-Ras, and c-Myc, with a higher expression in tumors, while
      premalignant mammary epithelial cells displayed an intermediate state between
      tumors and controls. In human clinical samples, reduced expression of BRCA1
      correlates with decreased levels of DNMT1, and reduced methylation of CpG
      islands. Thus, BRCA1 prevents global DNA hypomethylation through positively
      regulating DNMT1 expression, and this provides one of mechanisms for BRCA1
      associated breast cancer formation.

PMID- 20820193
TI  - Structural basis of immunosuppression by the therapeutic antibody daclizumab.
AB  - Interleukin-2 (IL)-2 signaling plays a pivotal role in the activation of immune
      responses, and drugs that block this pathway have been shown to be effective for
      the immunosuppression in patients with organ transplantation to
      alleviate/eliminate allograft rejection. The first humanized monoclonal antibody
      (mAb) daclizumab falls into this category and shows high specificity and affinity
      against a key component of the IL-2 receptor complex, namely IL-2Ralpha. To
      reveal the molecular mechanism of the inhibition of the IL-2 signaling pathway by
      daclizumab, we determined the crystal structures of the daclizumab Fab in free
      form and in complex with the IL-2Ralpha ectodomain at 2.6 and 2.8 A resolution,
      respectively. The daclizumab Fab adopts a similar conformation in the presence or
      absence of the IL-2Ralpha ectodomain. The antigen-binding site of daclizumab is
      mainly composed of five complementarity determining regions (CDRs) that form a
      large positively charged surface depression and two flanking patches that are
      generally hydrophobic. The conformational epitope consists of several
      discontinuous segments of the IL-2Ralpha ectodomain, a large portion of which
      overlaps with the regions that interact with IL-2, suggesting that the binding of
      daclizumab to IL-2Ralpha would prevent the IL-2 binding to IL-2Ralpha and the
      subsequent formation of the IL-2/IL-2Ralphabetagamma(c) complex, and therefore
      block the IL-2 signaling pathway. These results also have implications for the
      design and development of improved mAb drugs targeting IL-2Ralpha.

PMID- 20820194
TI  - PPARgamma: a circadian transcription factor in adipogenesis and osteogenesis.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a critical factor
      for adipogenesis and glucose metabolism, but accumulating evidence demonstrates
      the involvement of PPARgamma in skeletal metabolism as well. PPARgamma agonists,
      the thiazolidinediones, have been widely used for the treatment of type 2
      diabetes mellitus owing to their effectiveness in lowering blood glucose levels.
      However, the use of thiazolidinediones has been associated with bone loss and
      fractures. Thiazolidinedione-induced alterations in the bone marrow milieu-that
      is, increased bone marrow adiposity with suppression of osteogenesis-could
      partially explain the pathogenesis of drug-induced bone loss. Furthermore,
      several lines of evidence place PPARgamma at the center of a regulatory loop
      between circadian networks and metabolic output. PPARgamma exhibits a circadian
      expression pattern that is magnified by consumption of a high-fat diet. One gene
      with circadian regulation in peripheral tissues, nocturnin, has been shown to
      enhance PPARgamma activity. Importantly, mice deficient in nocturnin are
      protected from diet-induced obesity, exhibit impaired circadian expression of
      PPARgamma and have increased bone mass. This Review focuses on new findings
      regarding the role of PPARgamma in adipose tissue and skeletal metabolism and
      summarizes the emerging role of PPARgamma as an integral part of a complex
      circadian regulatory system that modulates food storage, energy consumption and
      skeletal metabolism.

PMID- 20820197
TI  - Periodontitis in RA-the citrullinated enolase connection.
AB  - Autoimmunity in rheumatoid arthritis (RA) is characterized by an antibody
      response to citrullinated proteins. Two of the risk factors for RA-HLA-DRB1
      shared epitope alleles and smoking-are also associated with periodontitis, which
      is largely, but not exclusively, caused by Porphyromonas gingivalis infection.
      Furthermore, RA and periodontitis have a similar pathophysiology, characterized
      by destructive inflammation. The citrullination of proteins by P. gingivalis and
      the subsequent generation of autoantigens that drive autoimmunity in RA
      represents a possible causative link between these two diseases. Antibodies
      directed towards the immunodominant epitope of human citrullinated alpha-enolase
      cross-react with a conserved sequence on citrullinated P. gingivalis enolase. On
      the basis of this cross-reactivity, in this Perspectives article we explore the
      hypothesis of molecular mimicry in the etiology of RA, with citrullinated enolase
      as the specific antigen involved.

PMID- 20820195
TI  - CGRP and its receptors provide new insights into migraine pathophysiology.
AB  - Over the past 300 years, the migraine field has been dominated by two main
      theories-the vascular theory and the central neuronal theory. The success of
      vasoconstrictors such as ergotamine and the triptans in treating acute migraine
      bolstered the vascular theory, but evidence is now emerging that vasodilatation
      is neither necessary nor sufficient to induce a migraine attack. Attention is now
      turning to the core migraine circuits in the brain, which include the trigeminal
      ganglia, trigeminal nucleus, medullary modulatory regions, pons, periaqueductal
      gray matter, hypothalamus and thalamus. Migraine triggers are likely to reflect a
      disturbance in overall balance of the circuits involved in the modulation of
      sensory activity, particularly those with relevance to the head. In this Review,
      we consider the evidence pointing towards a neuronal mechanism in migraine
      development, highlighting the role of calcitonin gene-related peptide (CGRP),
      which is found in small to medium-sized neurons in the trigeminal ganglion. CGRP
      is released during migraine attacks and can trigger migraine in patients, and
      CGRP receptor antagonists can abort migraine. We also examine whether other
      drugs, such as triptans, might exert their antimigraine effects via their actions
      on the neuronal circuit as opposed to the intracranial vasculature.

PMID- 20820196
TI  - Using pharmacokinetic principles to optimize pain therapy.
AB  - Cyclo-oxygenase (COX) inhibitors are widely used to relieve musculoskeletal pain.
      These agents block the production of prostaglandins (PGs) at sites of
      inflammation by inhibiting the activity of two COX enzymes necessary for PG
      production and normal organ homeostasis. Inhibition of PG production at sites
      unrelated to pain is associated with adverse drug reactions (ADRs). The degree of
      analgesic efficacy, as well as the incidence and the localization of ADRs, are
      critically influenced by the pharmacokinetics (absorption, distribution and
      elimination) of these drugs. Ideally, sufficient and permanent inhibition of COX
      enzymes should be achieved in target tissues, with minimal ADRs. To minimize
      underdosing or overdosing, which result in therapeutic failure or ADRs, the COX
      inhibitor with the most appropriate pharmacokinetic properties should be selected
      on the basis of a thorough pharmacokinetic-pharmacodynamic analysis. In this
      Review, the pharmacokinetics of the prevailing COX inhibitors will be discussed
      and enigmatic aspects of these intensively used drugs will be considered.

PMID- 20820199
TI  - Single laser source for multimodal coherent anti-Stokes Raman scattering
      microscopy.
AB  - Short laser pulse technology has significantly contributed to biomedical
      research, especially via nonlinear optical microscopy. Coherent anti-Stokes Raman
      scattering (CARS) microscopy is a label-free, chemical-selective method that is
      growing in importance as improved methods and light sources develop. Here we
      discuss different approaches to laser source development for CARS microscopy and
      highlight the advantages of a multimodal CARS microscope, illustrated by selected
      applications in biomedical research.

PMID- 20820198
TI  - Lasers in refractive surgery: history, present, and future.
AB  - The history of laser refractive surgery is reviewed, followed by an overview of
      the current state of the field as well as a look at promising future
      developments.

PMID- 20820200
TI  - Miniaturization of free space optical systems.
AB  - Coherent illumination enables not only integrated optics, but also miniaturized
      free-space optics that takes advantage of the amplitude and phase control
      afforded by optical microelectromechanical systems (MEMS) and photonic crystals.
      These technologies also provide a practical and cost-effective means for
      integration and packaging of optical systems. The properties of miniaturized
      optical systems based on optical MEMS and photonic crystals are described, and
      efficient analysis and design approaches to miniaturized optical scanners and
      tunable diffractive optical elements are demonstrated. The impact of photonic
      crystals on free-space micro-optics is discussed.

PMID- 20820201
TI  - History of quantum electronics at the Moscow Lebedev and General Physics
      Institutes: Nikolaj Basov and Alexander Prokhorov.
AB  - Some moments of maser and laser history in the Soviet Union are outlined,
      commemorating the work of Nikolaj G. Basov and Alexander M. Prokhorov, who,
      together with Charles H. Townes, were awarded the 1964 Nobel Prize "for
      fundamental work in the field of quantum electronics, which has led to the
      construction of oscillators and amplifiers based on the maser-laser principle."

PMID- 20820202
TI  - Dynamic holography using pixelated light modulators.
AB  - Dynamic holography using spatial light modulators is a very flexible technique
      that offers various new applications compared to static holography. We give an
      overview on the technical background of dynamic holography focusing on pixelated
      spatial light modulators and their technical restrictions, and we present a
      selection of the numerous applications of dynamic holography.

PMID- 20820203
TI  - Optical interconnects to electronic chips.
AB  - Optical interconnects are progressively replacing wires at shorter and shorter
      distances in information processing machines. This paper summarizes the progress
      toward and prospects for the penetration of optics all the way to the silicon
      chip.

PMID- 20820204
TI  - Fiber lasers and amplifiers: an ultrafast performance evolution.
AB  - The first rare-earth-doped fiber lasers were operated in the early sixties and
      produced a few milliwatts at a wavelength around 1 mum. For the next several
      decades, fiber lasers were little more than a low-power laboratory curiosity.
      Recently, however, fiber lasers are entering the realm of kilowatt powers in
      continuous as well as in pulse operation with diffraction-limited beam quality.
      In this article we review this power evolution.

PMID- 20820205
TI  - Laser-based displays: a review.
AB  - After the invention of lasers, in the past 50 years progress made in laser-based
      display technology has been very promising, with commercial products awaiting
      release to the mass market. Compact laser systems, such as edge-emitting diodes,
      vertical-cavity surface-emitting lasers, and optically pumped semiconductor
      lasers, are suitable candidates for laser-based displays. Laser speckle is an
      important concern, as it degrades image quality. Typically, one or multiple
      speckle reduction techniques are employed in laser displays to reduce speckle
      contrast. Likewise, laser safety issues need to be carefully evaluated in
      designing laser displays under different usage scenarios. Laser beam shaping
      using refractive and diffractive components is an integral part of laser
      displays, and the requirements depend on the source specifications, modulation
      technique, and the scanning method being employed in the display. A variety of
      laser-based displays have been reported, and many products such as pico
      projectors and laser televisions are commercially available already.

PMID- 20820206
TI  - A short history of laser development.
AB  - Half a century has passed since Theodore Maiman's small ruby rod crossed the
      threshold of laser emission. The breakthrough demonstration earned headlines, but
      in the early years the laser was called "a solution looking for a problem," and
      there was a germ of truth in the joke. Years of development since then have
      vastly improved laser performance,and tremendously increased their variety,
      earning lasers important roles in scientific research, consumer products,
      telecommunications,engineering, medicine, materials working, and a host of other
      applications. This article reviews the highlights of those developments and puts
      them into context, showing how laser technology has evolved to meet application
      requirements.

PMID- 20820207
TI  - Lasers: the first fifty years.
AB  - This year marks the 50th anniversary of the invention of the laser. The Optical
      Society of America is publishing this feature issue to celebrate this auspicious
      birthday.

PMID- 20820208
TI  - Development of microperiodic mirrors for hard x-ray phase-contrast imaging.
AB  - Differential phase-contrast imaging with hard x rays can have important
      applications in medicine, material sciences, and energy research. Phase-contrast
      methods based on microperiodic optics, such as shearing interferometry, are
      particularly attractive because they allow the use of conventional x-ray tubes.
      To enable shearing interferometry with x rays up to 100?keV, we propose using
      grazing-incidence microperiodic mirrors. In addition, a simple lithographic
      method is proposed for the production of the microperiodic x-ray mirrors, based
      on the difference in grazing-incidence reflectivity between a low-Z substrate and
      a high-Z film. Using this method, we produced prototype mirrors with 5-100?mum
      periods and 90?mm active length. Experimental tests with x rays up to 60?keV
      indicate good microperiodic mirror reflectivity and high-contrast fringe
      patterns, encouraging further development of the proposed imaging concept.

PMID- 20820209
TI  - Imaging linear polarimetry using a single ferroelectric liquid crystal modulator.
AB  - In the field of polarimetry, ferroelectric liquid crystal cells are mostly used
      as bistable polarization rotators suitable to analyze crossed polarizations. This
      paper shows that, provided such a cell is used at its nominal wavelength and
      correctly driven, its behavior is close to that of a tunable half-wave plate, and
      it can be used with much benefit in lightweight imaging polarimetric setups. A
      partial Stokes polarimeter using a single digital video camera and a single
      ferroelectric liquid crystal modulator is designed and implemented for linear
      polarization analysis. Polarization azimuthal angle and degree of linear
      polarization are available at 150 frames per second with a good accuracy.

PMID- 20820210
TI  - Coherent hollow-core waveguide bundles for thermal imaging.
AB  - There has been very little work done in the past to extend the wavelength range
      of fiber image bundles to the IR range. This is due, in part, to the lack of IR
      transmissive fibers with optical and mechanical properties analogous to the oxide
      glass fibers currently employed in the visible fiber bundles. Our research is
      aimed at developing high-resolution hollow-core coherent IR fiber bundles for
      transendoscopic infrared imaging. We employ the hollow glass waveguide (HGW)
      technology that was used successfully to make single-HGWs with Ag/AgI thin film
      coatings to form coherent bundles for IR imaging. We examine the possibility of
      developing endoscopic systems to capture thermal images using hollow waveguide
      fiber bundles adjusted to the 8-10?mum spectral range and investigate the
      applicability of such systems. We carried out a series of measurements in order
      to characterize the optical properties of the fiber bundles. These included the
      attenuation, resolution, and temperature response. We developed theoretical
      models and simulation tools that calculate the light propagation through HGW
      bundles, and which can be used to calculate the optical properties of the fiber
      bundles. Finally, the HGW fiber bundles were used to transmit thermal images of
      various heated objects; the results were compared with simulation results. The
      experimental results are encouraging, show an improvement in the resolution and
      thermal response of the HGW fiber bundles, and are consistent with the
      theoretical results. Nonetheless, additional improvements in the attenuation of
      the bundles are required in order to be able to use this technology for medical
      applications.

PMID- 20820211
TI  - Return-path, multiple-principal-angle, internal-reflection ellipsometer for
      measuring IR optical properties of aqueous solutions.
AB  - A retroreflection (return-path) spectroscopic ellipsometer without a wave plate
      is described that uses an IR-transparent high-refractive-index hemicylindrical
      semiconductor substrate to measure the optical properties of aqueous solutions
      from multiple principal angles and multiple principal azimuths of attenuated
      internal reflection (AIR) at the semiconductor-solution interface. The pseudo
      Brewster angle of minimum reflectance for the p polarization is also readily
      measured using the same instrument. This wealth of data can also be used to
      characterize thin films at the solid-liquid interface. Simulated results of AIR
      at the Si-water interface over the 1.2-11?mum IR spectral range are presented in
      support of this concept. The optical properties of water and aqueous solutions
      are important for modeling radiative transfer in the atmosphere and oceans and
      for biomedical and tissue optics.

PMID- 20820212
TI  - Analysis of inverse-Gaussian apodized fiber Bragg grating.
AB  - Inverse-Gaussian apodized fiber Bragg gratings (IGAFBGs) are numerically studied
      using the transfer matrix method and fabricated by the commonly used phase-mask
      scanning technique in a single-step scanning process. The IGAFBG can serve as a
      dual-wavelength passband filter, whose wavelength spacing can be continuously
      tuned by introducing a tunable chirp through applying a strain gradient in
      principle. Also, an IGAFBG with identical dual passbands having 0.144nm
      wavelength spacing is experimentally achieved. We also show that an IGAFBG can
      act as a multipassband filter with varied free spectral ranges (FSRs), and the
      largest FSR variation of this IGAFBG is nearly seven times more than that in a
      comparable FBG pair filter. An IGAFBG with varied FSRs of approximately 16.125,
      approximately 12.25, approximately 8.5, and approximately 6.375GHz is fabricated.
      This multipassband varying-FSR IGAFBG filter can find applications in step
      tunable microwave generations.

PMID- 20820213
TI  - Spectral dependence of the refractive index of chemical vapor deposition ZnSe
      grown on substrate with an optimized temperature increase.
AB  - Precise measurement of the refractive index of chemical vapor deposition (CVD)
      ZnSe with the Fourier-transform interference refractometry method from 0.9 to
      21.7microm (from 11,000 to 460cm(-1)) with 0.1cm(-1) resolution is described. For
      this measurement, structurally homogeneous ZnSe plates were grown on a substrate
      with an optimized temperature increase. Using three ZnSe plates of different
      thicknesses, we managed to raise the measurement accuracy of the refractive index
      up to 2x10(-5) (being nearly 1 order of magnitude better than the available data)
      in the near IR and most of the middle IR wavelength range from 0.9 to 12.5microm
      (wavenumber range of 11,000-800cm(-1)) and up to 1...4x10(-4) in the 12.5
      21.7microm (800-460cm(-1)) region. The experimental results are approximated by a
      generalized Cauchy dispersion function of the 8th power. Spectral wavelength
      dependencies of the first- and second-order derivatives of the refractive index
      are calculated, and the zero material dispersion wavelength is found to be
      lambda(0)=4.84microm.

PMID- 20820214
TI  - Fourier-transform absorption spectroscopy in reciprocating engines.
AB  - We have adapted our in-cylinder Fourier-transform spectroscopy technique to
      measure absorption spectra in a reciprocating engine. Previously, we had used the
      technique for emission spectroscopy; the upgrade to absorption spectroscopy mode
      is important because it allows for more quantitative analysis of gas properties
      than is possible with emission spectroscopy. Here, we discuss fuel, H(2)O, and
      CO(2) spectra measured in an engine using a spark-plug-based probe for optical
      access and use the water portion of the spectra to determine in-cylinder gas
      temperature. The temperature results show that heat transfer effects can
      significantly bias thermometry when fiber-coupled engine probes are used.

PMID- 20820215
TI  - Phase unwrapping for noisy phase maps using rotational compensator with virtual
      singular points.
AB  - In the process of phase unwrapping for an image obtained by an interferometer or
      in-line holography, noisy image data may pose difficulties. Traditional phase
      unwrapping algorithms used to estimate a two-dimensional phase distribution
      include much estimation error, due to the effect of singular points. This paper
      introduces an accurate phase-unwrapping algorithm based on three techniques: a
      rotational compensator, unconstrained singular point positioning, and virtual
      singular points. The new algorithm can confine the effect of singularities to the
      local region around each singular point. The phase-unwrapped result demonstrates
      that accuracy is improved, compared with past methods based on the least-squares
      approach.

PMID- 20820216
TI  - Improved technique for measuring full-field absolute phases in a common-path
      heterodyne interferometer.
AB  - When an asymmetric triangle voltage signal is applied to drive an electro-optic
      modulator, interference signals with two groups of periodic sinusoidal segments
      with different frequencies are obtained. An improved method is proposed to fit
      these two groups of segments, and their associated phases can be determined. The
      absolute phase can be obtained by subtracting the initial phase from the phases
      of these two groups. This technique is applied to all pixels, and the full-field
      absolute phase measurements can be achieved. The validity of this method is
      demonstrated.

PMID- 20820217
TI  - Experimental investigation of square dissipative soliton generation and
      propagation.
AB  - We have experimentally investigated the generation and propagation of square
      dissipative solitons emitted from an erbium-doped fiber laser with large normal
      cavity dispersion. The square pulse exhibits an approximately Gaussian spectral
      profile and large frequency chirp on its edges. When the square pulse propagates
      through a segment of single-mode fiber (SMF), it can be shaped to a Gaussian
      pulse and the corresponding spectrum will have a redshift with a prolonged wing
      on the longer wavelength. Our experiments show that the pulse evolution in the
      SMF is determined by the combined effects of the fiber dispersion, intrapulse
      Raman scattering, and the pulse initial chirps.

PMID- 20820218
TI  - Real-time processing for full-range Fourier-domain optical-coherence tomography
      with zero-filling interpolation using multiple graphic processing units.
AB  - The real-time display of full-range, 2048?axial pixelx1024?lateral pixel, Fourier
      domain optical-coherence tomography (FD-OCT) images is demonstrated. The required
      speed was achieved by using dual graphic processing units (GPUs) with many stream
      processors to realize highly parallel processing. We used a zero-filling
      technique, including a forward Fourier transform, a zero padding to increase the
      axial data-array size to 8192, an inverse-Fourier transform back to the spectral
      domain, a linear interpolation from wavelength to wavenumber, a lateral Hilbert
      transform to obtain the complex spectrum, a Fourier transform to obtain the axial
      profiles, and a log scaling. The data-transfer time of the frame grabber was
      15.73?ms, and the processing time, which includes the data transfer between the
      GPU memory and the host computer, was 14.75?ms, for a total time shorter than the
      36.70?ms frame-interval time using a line-scan CCD camera operated at 27.9?kHz.
      That is, our OCT system achieved a processed-image display rate of 27.23
      frames/s.

PMID- 20820219
TI  - Fingerprint sensor using a polymer dispersed liquid crystal holographic lens.
AB  - We used a polymer dispersed liquid crystal material holographic lens in a
      fingerprint sensor, which reduced the total size of the sensor and improved image
      quality. The beam carrying fingerprint information was diffracted by the
      holographic lens and converged onto the complementary metal-oxide semiconductor
      image sensor directly, which omitted the traditional lens or fiber taper. The
      phenomenon that the image quality is poor when the finger is too dry or wet was
      explained based on the evanescent wave theory. The total size of the device was
      50 mm x 25 mm x 30 mm. The fingerprint image had a contrast of 250:1 and a
      resolution of 800 dots/in.

PMID- 20820220
TI  - Resonant soft x-ray reflectivity of Me/B(4)C multilayers near the boron K edge.
AB  - Energy dependence of the optical constants of boron carbide in the short period
      Ru/B(4)C and Mo/B(4)C multilayers (MLs) are evaluated from complete reflectivity
      scans across the boron K edge using the energy-resolved photon-in-photon-out
      method. Differences between the refractive indices of the B(4)Cmaterial inside
      and close to the surface are obtained from the peak profile of the first order ML
      Bragg peak and the reflection profile near the critical angle of total external
      reflection close to the surface. Where a Mo/B(4)C ML with narrow barrier layers
      appears as a homogeneous ML at all energies, a Ru/B(4)C ML exhibits another
      chemical nature of boron at the surface compared to the bulk. From evaluation of
      the critical angle of total external reflection in the energy range between 184
      and 186eV, we found an enriched concentration of metallic boron inside the Ru
      rich layer at the surface, which is not visible in other energy ranges.

PMID- 20820221
TI  - Optical configurations for nematic liquid crystal device switchable between
      reflective and transmissive modes.
AB  - We propose an optical configuration for a nematic liquid crystal (LC) device that
      is switchable between the reflective and the transmissive modes. By placing a
      reflective polarizer between the two LC layers, we obtain higher reflectance and
      reduce the parallax effect in the reflective mode. We can eliminate the parallax
      effect by using a wire-grid polarizer or other in-cell reflective polarizers. We
      expect that the proposed device can be used in various outdoor applications.

PMID- 20820222
TI  - Photonic bandgap fiber bundle spectrometer.
AB  - By using a photonic bandgap (PBG) fiber bundle and a monochrome CCD camera, we
      experimentally demonstrate an all-fiber spectrometer. A total of 100 Bragg fibers
      that have complementary and overlapping bandgaps are chosen to compose the fiber
      bundle. A monochrome CCD is then used to capture the binned image. To reconstruct
      the test spectrum from a single CCD image, we develop an algorithm based on
      pseudoinversion of the spectrometer transmission matrix. We demonstrate that the
      peak center wavelength can always be reconstructed within several percent of its
      true value regardless of the peak width or position, and that, although the
      widths of the individual Bragg fiber bandgaps are quite large (60-180nm), the
      spectroscopic system has a resolution limit of approximately 30nm. Moreover, we
      conclude that, by minimizing system errors, the resolution can be further
      improved down to several nanometers in width. Finally, we report fabrication of
      PBG fiber bundles containing hundreds of fibers using a two-stage drawing
      technique. This method constitutes a very promising approach toward industrial
      strength fabrication of all-fiber spectrometers.

PMID- 20820223
TI  - Simple approach to the relation between laser frequency noise and laser line
      shape.
AB  - Frequency fluctuations of lasers cause a broadening of their line shapes.
      Although the relation between the frequency noise spectrum and the laser line
      shape has been studied extensively, no simple expression exists to evaluate the
      laser linewidth for frequency noise spectra that does not follow a power law. We
      present a simple approach to this relation with an approximate formula for
      evaluation of the laser linewidth that can be applied to arbitrary noise spectral
      densities.

PMID- 20820224
TI  - Buffering capability and limitations in low dispersion photonic crystal
      waveguides with elliptical airholes.
AB  - A low dispersion photonic crystal waveguide with triangular lattice elliptical
      airholes is proposed for compact, high-performance optical buffering
      applications. In the proposed structure, we obtain a negligible-dispersion
      bandwidth with constant group velocity ranging from c/41 to c/256, by optimizing
      the major and minor axes of bulk elliptical holes and adjusting the position and
      the hole size of the first row adjacent to the defect. In addition, the
      limitations of buffer performance in a dispersion engineering waveguide are well
      studied. The maximum buffer capacity and the maximum data rate can reach as high
      as 262bits and 515 Gbits/s, respectively. The corresponding delay time is about
      255.4ps.

PMID- 20820225
TI  - Theory of point-spread function artifacts due to structured mid-spatial frequency
      surface errors.
AB  - Optical design and tolerancing of aspheric or free-form surfaces require
      attention to surface form, structured surface errors, and nonstructured errors.
      We describe structured surface error profiles and effects on the image point
      spread function using harmonic (Fourier) decomposition. Surface errors over the
      beam footprint map onto the pupil, where multiple structured surface frequencies
      mix to create sum and difference diffraction orders in the image plane at each
      field point. Difference frequencies widen the central lobe of the point-spread
      function and summation frequencies create ghost images.

PMID- 20820226
TI  - Theory of modulation transfer function artifacts due to mid-spatial-frequency
      errors and its application to optical tolerancing.
AB  - Aspheric and free-form surfaces are powerful surface forms that allow designers
      to achieve better performance with fewer lenses and smaller packages. Unlike
      spheres, these surfaces are fabricated with processes that leave a signature, or
      "structure," that is primarily in the mid-spatial-frequency region. These
      structured surface errors create ripples in the modulation transfer function
      (MTF) profile. Using Fourier techniques with generalized functions, the drop in
      MTF is derived and shown to exhibit a nonlinear relationship with the peak-to
      valley height of the structured surface error.

PMID- 20820227
TI  - Multimode excitation-induced phase shifts in intrinsic Fabry-Perot
      interferometric fiber sensor spectra.
AB  - We report the modal analysis of optical fiber single-mode-multimode-single-mode
      intrinsic Fabry-Perot interferometer sensors. The multimode nature of the Fabry
      Perot cavity gives rise to an additional phase term in the spectrogram due to
      intermodal dispersion-induced wavefront distortion, which could significantly
      affect the cavity length demodulation accuracy. By using an exact model to
      analyze the modal behavior, this phase term is explained by employing a rotating
      vector approach. Comparison of the theoretical analysis with experimental results
      is presented.

PMID- 20820228
TI  - Patents.
AB  - 4,884,874; 4,886,343; 4,884,874; 4,886,343; 4,902,108; 4,913,531; 4,925,276;
      4,948,229; 4,964,684; 4,968,119; 4,968,120; 5,050,992; 5,051,571; 5,052,764;
      5,052,765; 5,056,880; 5,056,901; 5,058,977; 5,059,027; 5,059,786; 5,061,025;
      5,061,032; 5,062,094; 5,063,292; 5,063,586; 5,063,781; 5,064,259; 5,064,262;
      5,067,782; 5,067,805; 5,069,532; 5,076,669; 5,080,490; 5,083,866; 5,090,795;
      5,090,811; 5,092,342; 5,094,526; 5,102,222; 5,104,221; 5,104,224; 5,105,305;
      5,106,193; 5,107,526; 5,108,183; 5,110,210; 5,112,121; 5,115,137; 5,118,181;
      5,121,257; 5,121,978; 5,122,650; 5,125,743; 5,130,546; 5,131,023; 5,134,521;
      5,134,523; 5,278,482.

PMID- 20820229
TI  - Vacuum activated polishing laps produce smooth aspheric surfaces.
AB  - A novel approach to computer controlled fabrication of aspheric optical surfaces
      utilizes semi-flexible vacuum activated polishing tools to produce high quality,
      smooth surface geometry on off-axis mirror components.

PMID- 20820230
TI  - Precision measurements of the optical attenuation profile along the propagation
      path in thin-film waveguides.
AB  - An experimental technique for precision measurements of the optical attenuation
      profile along a propagation path in thin-film waveguides is reported. The method
      involves a 100% outcoupling of guided light through immersion of the waveguide
      into a liquid with an index of refraction slightly higher than that of the film.
      The measurement is simple and nondestructive. The repeatability and accuracy of
      the measured attenuation per unit length is typically better than 5%, even with
      losses below 0.1 dB/cm and less than 1-cm-long guiding paths.

PMID- 20820231
TI  - Absolute flatness testing by an extended rotation method using two angles of
      rotation.
AB  - The rotation method for the absolute testing of three flats is extended by adding
      a second rotation of one of the flats. This means that altogether five
      interferograms of pairs of flats (positional combinations) are evaluated: three
      basic combinations and two rotational combinations. The effect of random
      measuring errors is minimized by fully applying least-squares methods. Here the
      addition of a second rotation leads to a substantial increase of accuracy of the
      results and enables the lateral resolution to be further enhanced.

PMID- 20820232
TI  - Profile measurements of cylindrical surfaces.
AB  - We introduce an interferometric method for measuring the profiles of cylindrical
      surfaces. A Fizeau interferometer with a flat reference is used to test part of a
      cylindrical surface, and various parts of the surface can be tested by the
      rotation of the surface. The algorithm for linking separate measurements is
      described, and testing examples for measuring sagitta over 3 mm of a cylindrical
      surface with an elliptical cross section are included. Measurement results show
      that repeatability for the above test to the order of 1 microm, is feasible.

PMID- 20820233
TI  - Experimental investigation of memory effects in intensified photodiode-array
      spectrograph detectors.
AB  - The use of intensified linear photodiode arrays as spectrograph detectors can, in
      certain applications, be subject to interference by several side effects. The
      widely used P-20 phosphor of the image intensifier exhibits both phosphorescence
      decay (persistence) and thermoluminescence memory effects together with an
      inherent nonlinear response to incident light, whereas the photodiode array
      exhibits a readout-lag memory effect. During characterization of any one of these
      effects, it was important to ensure that the measurements were not influenced by
      the other side effects. This was particularly true for the phosphorescence and
      readout-lag effects, and for the thermoluminescence and inherent phosphor
      nonlinearity effects. These side effects become significant in applications where
      spectra that exhibit large changes in shape and intensity on a pulse-by-pulse
      basis are being recorded individually at rates > 0.1 Hz. A determination should
      then be made to either correct, circumvent, or ignore these potential sources of
      error.

PMID- 20820234
TI  - Talbot plane patterns: grating images or interference effects?
AB  - It has been widely said that with the Talbot effect a grating makes images of
      itself unaided. However, the effect as produced by simple amplitude gratings was
      recently redefined in terms of interference-pattern visibility or contrast
      instead of self-imaging. Then, by starting with a pair of slits instead of the
      usual infinite grating, a new and more general description of the effect was
      developed. Now numerical methods and tools from physical optics are used further
      to characterize the influences of the grating, light parameters, and the position
      of the plane of observation on pattern form, fine structure, band positions, and
      phases. It is found that none of the patterns in the Talbot planes actually
      approximates grating images in terms of all of these properties. Hence the Talbot
      effect should be defined in terms of interference effects, not grating images.

PMID- 20820235
TI  - Beam quality changes in Hermite-Gauss mode fields propagating through Gaussian
      apertures.
AB  - The beam quality behavior of Hermite-Gauss laser modes propagating through
      Gaussian apertures is analyzed.

PMID- 20820236
TI  - Temporal averaging of phase measurements in the presence of spurious phase drift:
      application to phase-stepped real-time holographic interferometry.
AB  - A technique that compensates for low spatial frequency spurious phase changes
      during an interference experiment is developed; it permits temporal averaging of
      multiple phase measurements, made before and after object displacement. The
      method is tested with phase-stepped real-time holographic interferometry applied
      to cantilever bending of a piezoelectric bimorph ceramic. Results indicate that
      temporal averaging of the corrected data significantly reduces the white noise in
      a phase measurement without incurring systematic errors or sacrificing spatial
      resolution. White noise is reduced from 3 degrees to less than 1 degrees
      (lambda/360) using these methods.

PMID- 20820237
TI  - Fabry-Perot wavemeter for shot-by-shot analysis of pulsed lasers.
AB  - A Fabry-Perot wavemeter for analyzing a pulsed laser operating in a single
      longitudinal mode with an injection-seeding technique has been constructed with
      an array detector. This wavemeter permits the real-time measurement of both the
      wavelength and the spectral effectiveness of the laser pulse produced at 10 Hz.
      The performance of the wavemeter is checked with a frequency-stabilized He-Ne
      laser and a double Nd:YAG laser that operates in the single longitudinal mode.
      The precision of the wavemeter is found to be < 10 MHz. Also, we calculated the
      uncertainties in determining the wave number by processing a Fabry-Perot fringe
      pattern imaged on a linear-array detector. The calculation is done by changing
      the number of pixels of the array detector, the finesse of the Fabry-Perot
      etalon, the waist of the incident laser beam, and the magnitude of random noise.

PMID- 20820238
TI  - Partially multiplexing sensor network exploiting low coherence interferometry.
AB  - A partially multiplexed fiber-optic-based sensor network based on low coherence
      interferometry is reported for which the scanning interferometer simultaneously
      sweeps the coherence-matched region of each sensor. The advantage of this
      approach is that the signal-to-noise ratio is maximized while the cross talk
      between sensors is minimized. The normal requirement that each sensor must be
      fabricated with a different length also does not apply. The concept is
      demonstrated by multiplexing two bulk optic Michelson interferometers. A
      resolution of ~ 50 nm with an operational range of 200 microm was achieved in the
      prototype system.

PMID- 20820239
TI  - Flattening the field of postobjective scanners by optimum choice and positioning
      of polygons.
AB  - Polygonal mirrors are commonly used in laser beam scanning. The paper gives some
      useful geometrical formulas for their basic dimensions when used as parallel as
      well as convergent beam scanners. The first part deals with underfilled polygons
      that are used in parallel beam scanning. In the second part, a method is outlined
      for obtaining a nearly flat field in convergent beam scanning. This method
      enables the use of relatively fast but simple spot-forming lenses in
      postobjective scan systems resulting in scan resolutions that are sometimes
      comparable to the resolutions given by preobjective scanners with complex F-theta
      lenses.

PMID- 20820240
TI  - Talbot array illuminator with multilevel phase gratings.
AB  - Construction of one-dimensional multilevel phase gratings is described that, when
      illuminated by a coherent plane wave, lead to the formation of amplitude binary
      gratings with an arbitrary value of the opening ratio. The gratings are proposed
      as array illuminators that can provide a significantly high compression factor
      together with a large number of uniformly illuminated points.

PMID- 20820241
TI  - Diffuse reflectance from turbid media: an analytical model of photon migration.
AB  - To calculate the diffuse reflectance from a semi-infinite slab of tissue, we
      introduce a probability distribution function, f(n)(g), that a photon will escape
      from the tissue after n scattering events. This approach permits the separation
      of the phase dependence of scattering, described by the anisotropy coefficient,
      g, from the absorption, micro(alpha), and scattering, micro(s), coefficients in
      the calculation of diffuse reflectance. We demonstrate that f(n)(g) and g are
      related to each other through a universal probability function. The analytical
      form of this probability function is explored and used to obtain the diffuse
      reflectance from tissue. The diffuse reflectance calculated with this method is
      in excellent agreement with Monte Carlo simulations over the parameter range
      typically found in human tissue, even for the values in which diffusion theory is
      a poor approximation.

PMID- 20820242
TI  - Theoretical dependence of infrared absorption in bulk-doped silicon on carrier
      concentration.
AB  - The infrared optical constants (index of refraction and extinction coefficient)
      and absorptance for doped bulk n-Si are calculated for electron concentrations as
      high as 1.3 x 10(20) cm(-3). These calculations are based on the generalized
      Drude-Lorentz approximation and predict nonmonotonic behavior of absorption as a
      function of electron concentration.

PMID- 20820243
TI  - Comparison between the optical constants obtained by the Kramers-Kronig analysis
      and the maximum entropy method: infrared optical properties of orthorhombic
      sulfur.
AB  - The optical constants of orthorhombic sulfur computed by the Kramers-Kronig phase
      shift analysis were recently reported by Fuller et al. The results obtained by
      Fuller et al. are compared with the ones obtained by a novel maximum entropy
      procedure.

PMID- 20820244
TI  - Resonance diffraction efficiency enhancement in sliced multilayers.
AB  - The theory of transmission and reflection sliced multilayers is considered. The
      possible scheme of a high throughput and resolution spectrograph for the 124-250
      A range is proposed.

PMID- 20820245
TI  - Deposition and characterization of far-infrared absorbing gold black films.
AB  - A process is described for producing gold black films with high absorptance in
      the far IR. The optical and electrical properties of these films have been
      studied with particular emphasis on the absorptance of films at wavelengths as
      long as 50 microm. A substantial decrease in absorptance near50 microm has been
      observed for pure gold black films on aging in air. This degradation can be
      largely avoided by alloying the gold with a small percentage of copper during the
      deposition. Preliminary results on two methods for delineating gold black films
      are also presented.

PMID- 20820246
TI  - Graded-reflectance mirrors for beam quality control in laser resonators.
AB  - Several types of small-dimension graded-reflectance mirrors deposited through
      rotating masks are compared. Multilayer mirrors provided with single-variable
      thickness layers have limitations that are avoided when all the layers in the
      system are shaped. High-reflectance mirrors of the latter type are demonstrated.
      Numerical and experimental results are given.

PMID- 20820247
TI  - Antireflection structured surfaces for the infrared spectral region.
AB  - Antireflection structured (ARS) surfaces on GaAs substrates for application with
      normally incident, randomly polarized, 10.6-microm-wavelength radiation are
      designed and analyzed. Both one-dimensional (1-D) and two-dimensional (2-D)
      multilevel profiles are examined with special attention given to multilevel
      approximations of 1-D triangular and 2-D pyramidal profiles. The 1-D profiles are
      designed by using second-order effective medium theory (EMT), as we have found
      zeroth-order EMT to be insufficient when ARS surfaces are designed for use with
      optically dense materials, e.g., most materials used in the infrared spectral
      region. We analyze both 1-D and 2-D profiles by using rigorous coupled-wave
      analysis and find that the more levels the profile contains, the better the ARS
      surface's response to bias angles, wavelength detunings, and errors in etch
      depth. Although both 1-D and 2-D profiles can efficiently suppress reflections
      for unpolarized light, 2-D gratings are advantageous when randomly polarized
      light is of interest.

PMID- 20820248
TI  - Determination of the optical constants (n, k) of thin dielectric films.
AB  - A method for the determination of the optical constants and the thickness of thin
      dielectric films on transparent substrates is proposed. It requires measurements
      at normal incidence of the transmission from two films of different thicknesses.
      The derivation is complicated by the existence of multiple solutions of the
      relevant equations. A procedure is given for determining the correct solutions
      for the indices of refraction and absorption and also for accurately fixing the
      thickness of the films. Advantages of the present method over existing methods
      are better accuracy and readily available measurement facilities. The method has
      been applied successfully to films of titanium oxide.

PMID- 20820249
TI  - Determination of the refractive index of a-Si(1-x)C(x):H thin films from infrared
      absorption spectra.
AB  - The index of refraction of a-Si(1-x)C(x):H thin films obtained by dc magnetron
      sputtering was determined by means of IR absorption measurements. Structural and
      compositional changes that take place by increasing x make the film a mixture of
      different species, giving an effective value of the refractive index.

PMID- 20820250
TI  - Immersion grating for infrared astronomy.
AB  - An immersion grating with high refractive index n increases spectral resolution n
      fold over that of a surface reflection grating of equal length.

PMID- 20820251
TI  - Differential equation design of finite-conjugate reflective systems.
AB  - Based on the conditions of aplanatism, a differential equation design method has
      been applied to the optimization of finite-conjugate, multimirror systems for
      soft x-ray applications. The shapes of two surfaces in a multimirror system are
      determined by numerically solving differential equations for the mirror surfaces.
      The shapes of other mirrors in the system are used to control the remaining
      aberrations of those systems, such as astigmatism, field curvature, and
      distortion. Applications include a three-minor projection-lithography system,
      which has been optimized by this method and compared with results obtained by
      conventional optical design, and a two-mirror soft x-ray imaging microscopy
      system, which is predicted to yield a diffraction-limited performance for a large
      N.A.

PMID- 20820252
TI  - Ross null test for conic mirrors.
AB  - Various refractive null-testing arrangements have been used over the years for
      testing concave nonspherical mirrors. This paper presents a method for null
      testing that uses a single plano-convex lens to compensate for the spherical
      aberration of a concave conic mirror when tested at its center of curvature. This
      testing method, called the Ross null test, requires a high-quality null lens and
      a standard Foucault test apparatus. This paper presents graphical and numerical
      data that provide the necessary parameters for implementing the Ross null test
      for mirrors with focal ratios ranging from f/3.5 to f/10 and for conic
      deformations ranging from eccentricities of 0.70-1.50.

PMID- 20820253
TI  - Calibrated real-time control of lesion size based on reflectance images.
AB  - Lesion size induced by laser photocoagulation is controlled in real time based on
      a two-dimensional reflectance image recorded by a CCD array during lesion
      formation. A feedback system using components of the reflectance image achieves
      uniform lesions by compensating for light absorption variability in biological
      media. Lesions are formed in a phantom by an argon laser to simulate retinal
      photocoagulation. The tissue model consists of a thin absorptive layer covered by
      a clear albumin protein layer. Results show a low variance in the sizes of the
      lesions (diameter or depth) produced in different irradiation conditions and the
      ability to produce lesions of a predefined size in varying illumination
      conditions.

PMID- 20820254
TI  - Method for accurate optical alignment using diffraction rings from lenses with
      spherical aberration.
AB  - A useful alignment method is presented that exploits the closely spaced
      concentric fringes that form in the longitudinal spherical aberration region of
      positive spherical lenses imaging a point source. To align one or more elements
      to a common axis, spherical lenses are attached precisely to the elements and the
      resulting diffraction rings are made to coincide. We modeled the spherical
      aberration of the lenses by calculating the diffraction patterns of converging
      plane waves passing through concentric narrow annular apertures. The validity of
      the model is supported by experimental data and is determined to be accurate for
      a prototype penumbral imaging alignment system developed at Lawrence Livermore
      National Laboratory.

PMID- 20820255
TI  - Metrology of lithographic features: balanced illumination eliminating diffractive
      bias.
AB  - Optical microscope metrology of shallow relief patterns is shown to be capable of
      greater accuracy, to smaller dimensions, when phase features are imaged rather
      than intensity ones. This comes from the inherent symmetry in diffraction from
      pure phase discontinuities. Thus when intensity variations are suppressed, as by
      appropriate illumination or filtering, the diffractive bias can be eliminated.
      The approach is analyzed and demonstrated. When it can be used, greater accuracy
      is available than with traditional approaches. In ideal conditions the approach
      has the potential for absolute accuracy within 0.1lambda, down to dimensions of
      <O.4lambda. Applications include binary and integrated optics and integrated
      circuits.

PMID- 20820256
TI  - Fiber sensor for the simultaneous measurement of current and voltage in a high
      voltage system.
AB  - A sensor employing a single monomode low-birefringence fiber, excited with a
      632.8-nm He-Ne laser, has been developed for the simultaneous measurement of
      current and voltage in an energy system. The piezoelectric effect for the voltage
      and the magnetic stress for the current are utilized. The current and voltage
      signals are separated at the detector end by suitable self-tracking tuned
      filters. Experimental results from a laboratory model demonstrate the feasibility
      of the sensor for field application in high-voltage systems.

PMID- 20820257
TI  - Detection of x rays with a fiber-optic interferometric sensor.
AB  - A fiber-optic Mach-Zehnder interferometer was used for x-ray detection. A single
      mode, polarization-preserving silica fiber is exposed to a high-flux x-ray beam
      (x-ray tube for diagnostic radiology, 30 kV, 16.8-keV average energy, 17-40-mA
      anodic current), modulated at f = 9 Hz by a chopper with steel blades. The energy
      absorbed produces a modulated temperature rise that induces a phase shift in the
      propagation of a He-Ne laser beam with respect to the unirradiated arm of the
      interferometer. We measured the linearity of the temperature rise with the energy
      released to the fiber and the linearity of the peak amplitude at frequency f in
      the power spectrum of the interferometric signal with the anodic current of the x
      ray tube. A possible application of this technique to synchrotron radiation
      monitoring is discussed.

PMID- 20820258
TI  - Comparison of methods for generation of absolute reflectance-factor values for
      bidirectional reflectance-distribution function studies.
AB  - Currently, spectrophotometric standard reference materials are calibrated only by
      using the illumination and viewing geometries recommended by the Commission
      Internationale de l'Eclairage, and for some geometries the spectral range is
      limited to the visible wavelengths. A need exists for procedures that calibrate
      standards at many other geometries and for a broader spectral range. Two methods
      for calibrating the spectral bidirectional reflectance factor are described. The
      absolute bidirectional reflectance factor of a sintered polytetrafluoroethylene
      (PTFE) sample is determined for nearly all the possible illumination and viewing
      geometries from 400 nm to 2500 nm. The references are a 45/0 reflectance standard
      calibrated by the National Institute of Standards and Technology and a sintered
      PTFE sample with a directional, hemispherical reflectance factor traceable to the
      Institute. The results of the two methods agree to within 0.01 in reflectance
      factor values. With this PTFE sample as a transfer standard, the instrument
      described can also be used to measure the absolute bidirectional reflectance
      factor at nearly all the illumination and viewing geometries from 400 nm to 2500
      nm.

PMID- 20820259
TI  - Optical neural networks: an introduction by the feature editors.
AB  - This feature of Applied Optics is devoted to papers on the optical implementation
      of neural-network models of computation. Papers are included on optoelectronic
      neuron array devices, optical interconnection techniques using holograms and
      spatial light modulators, optical associative memories, demonstrations of
      optoelectronic systems for learning, classification, and target recognition, and
      on the demonstration, analysis, and simulation of adaptive interconnections for
      optical neural networks using photorefractive volume holograms.

PMID- 20820260
TI  - Optical learning neurochip with internal analog memory.
AB  - An optical neurochip with learning capability and a memory function is reported
      for the first time, to our knowledge. The neurochip is a three-dimensional
      optoelectronic integrated circuit consisting of a light-emitting diode array and
      a variable-sensitivity photodetector array. The principle of operation and the
      fundamental characteristics of the neurochip are described in detail. The
      synaptic weights, which, are acquired through learning, are stored in the
      variable-sensitivity photodetector as the detection sensitivity with analog
      values. Both the positive and the negative synaptic weights are memorized with
      one variable-sensitivity photodetector element by changing the polarity of the
      electric signal applied to the photodetector. A storage time of ~20 min. was
      obtained. With a fabricated optical neurochip that had 32 neurons and 32 x 32
      synapses, experiments of on-chip learning for pattern classification were
      performed successfully.

PMID- 20820261
TI  - GaAs optoelectronic neuron arrays.
AB  - A simple optoelectronic circuit integrated monolithically in GaAs to implement
      sigmoidal neuron responses is presented. The circuit integrates a light-emitting
      diode with one or two transistors and one or two photodetectors. The design
      considerations for building arrays with densities of up to 10(4) cm(-2) are
      discussed.

PMID- 20820262
TI  - Optoelectronic array that computes error and weight modification for a bipolar
      optical neural network.
AB  - The design, fabrication, and results of an optoelectronic device that computes
      the weight changes required by the delta-rule learning algorithm and encodes the
      result on a pair of optical beams are presented. This very-large-scale-integrated
      ferroelectric liquid-crystal array was designed specifically to permit bipolar
      optoelectronic neural networks to learn without the limitations of an external
      controlling computer. The device contains 64 smart pixels, which represent the
      processing elements in an artificial neural network. Each processing element
      consists of two photodetectors, a current-to-voltage converter, two comparators,
      two switches, and two output liquid-crystal modulating pads. The device has a
      measured contrast ratio of 10:1, a 10%-to-90% rise time of 350 micros, and a 90%
      to-10% fall time of 150 micros.

PMID- 20820263
TI  - Optical implementation and applications of closest-vector selection in neural
      networks.
AB  - Closest-vector selection is a process that underlies one technique for sending
      compressed-signal sets over noisy communication channels. Recently it has had
      application in radar target identification, speech and image analysis, pattern
      classification, and neural-net training. Various applications of closest-vector
      selection are discussed, and the design of an all-optical system that performs
      closest-vector selection is presented.

PMID- 20820264
TI  - Computer-generated holograms for optical neural networks: on-axis versus off-axis
      geometry.
AB  - For optical neural networks implemented with computer-generated planar holograms
      the spacebandwidth product of the hologram is a major consideration. Off-axis
      holograms can be fabricated with a single binary transmission mask. However, the
      carrier frequency greatly increases the space-bandwidth product. On axis
      holograms use a lower space-bandwidth product to encode interconnections but
      require a multilevel phase transmission profile. Significant errors can result
      during the fabrication of multilevel phase structures. With modification of the
      on-axis geometry the effects of the fabrication errors can be reduced while a
      lower space-bandwidth product per interconnection is retained. The
      interconnection accuracy, the diffraction efficiency, the and sensitivity to
      fabrication errors are compared for the off-axis, the on-axis, and the modified
      on-axis diffraction geometries.

PMID- 20820265
TI  - Optical implementation of a second-order translation-invariant network algorithm.
AB  - Higher-order networks, particularly second-order translation-invariant networks,
      are introduced, and their suitability for optical implementation is outlined. The
      algorithm is implemented with a conventional liquid-crystal display, permitting
      on-line learning and updating of weights. The basic operation of the optical
      system is demonstrated, and the ability of the system to adapt to system
      nonuniformities is illustrated. The implementation with an integrated
      optoelectronic array of asymmetric Fabry-Perot modulators containing a
      GaAs/AlGaAs multiple-quantum-well active region is described. The principles of
      operation and operating characteristics of the device array are outlined. The use
      of the array in an optical system to calculate the autocorrelation matrix
      necessary for a second-order network is demonstrated.

PMID- 20820266
TI  - Gray-level discrete associative memory.
AB  - A gray-level discrete associative-memory neural network based on object
      decomposition and composition is presented. By decomposing a gray-level pattern
      into bipolar/binary subpatterns, a gray-level discrete associative memory can be
      constructed from the composition of the subpattern channel results. Preprocessing
      for removing dc bias and normalizing the gray-level scale is performed on the
      input gray-level pattern. This eliminates the mismatching and saturation problems
      caused by bias level, which shifts the pattern gray levels throughout the
      pattern. Computer-simulation and optical-experimental results for a gray-level
      interpattern association model are shown to be consistent with the theoretical
      model.

PMID- 20820267
TI  - Four-quadrant optical matrix-vector multiplication machine as a neural-network
      processor.
AB  - Optical processors for neural networks are primarily fast matrix-vector
      multiplication machines that can potentially compete with serial computers owing
      to their parallelism and their ability to facilitate densely connected networks.
      However, in most proposed systems the multiplication supports only two quadrants
      and is thus unable to provide bipolar neuron outputs for increasing network
      capabilities and learning rate. We propose and demonstrate an opto-electronic
      four-quadrant matrix-vector multiplier that can be used for feed-forward neural
      network recall and learning. Experimental results obtained with common commercial
      components demonstrate a novel, useful, and reliable approach for fourquadrant
      matrix-vector multiplication in general and for feed-forward neural-network
      training and recall in particular.

PMID- 20820268
TI  - Optical matrix-vector implementation of the content-addressable network.
AB  - The content-addressable network (CAN) is an efficient, intrinsically discrete
      training algorithm for binary-valued classification networks. The binary nature
      of the CAN network permits accelerated learning and significantly reduced
      hardware-implementation requirements. A multilayer optoelectronic CAN network
      employing matrix-vector multiplication was constructed. The network learned and
      correctly classified trained patterns, gaining a measure of fault tolerance by
      learning associative solutions to optical hardware imperfections. Operation of
      this system is possible owing to the reduced hardware accuracy requirements of
      the CAN learning algorithm.

PMID- 20820269
TI  - Optical perceptron learning for binary classification with spatial light
      rebroadcasters.
AB  - Binary classification of an object in a two-dimensional image is considered. A
      spatial light rebroadcaster is shown to be advantageous for learning in this case
      because it can store the weights and permit upward and downward adjustments. Two
      learning algorithms, based on the perceptron, are considered. A modification of
      the perceptron algorithm is developed so that only positive weights are needed.
      This is convenient because light intensity is positive only. The modified
      algorithm is shown to converge in a finite number of steps for positive linear
      separable classes. Optical experiments show the classification of four characters
      in two groups, in which alternative groupings are used to show robustness. In the
      second group of experiments the complements of the two-dimensional characters are
      used, and the convergence is equally fast. Adding the results from the original
      and complementary patterns provides a discrimination superior to that obtained
      using either on its own.

PMID- 20820270
TI  - Adaptive optical processing system with optical associative memory.
AB  - An architecture for a novel adaptive optical processing system using optical
      associative memory with learning capability is proposed. The optical system
      consists of an optical preprocessor for feature extraction and optical
      associative memory. The feature-extraction ability can give excellent processing
      capability to the optical associative memory. In order to demonstrate this
      system, an optical Fourier transform is used as the preprocessor, and the system
      can achieve shift invariance. An all-optical configuration of the system is
      proposed, and the experimental results applied to handwritten-character
      recognition by using an hybrid opto-electronic system are shown and discussed.

PMID- 20820271
TI  - Optical implementation of a feature-based neural network with application to
      automatic target recognition.
AB  - An optical neural network based on the neocognitron paradigm [IEEE Trans. Syst.
      Man Cybern. SMC-13, 826-834 (1983)] is introduced. A novel aspect of the
      architectural design is shift-invariant multichannel Fourier optical correlation
      within each processing layer. Multilayer processing is achieved by feeding back
      the output of the feature correlator iteratively to the input spatial light
      modulator and by updating the Fourier filters. By training the neural net with
      characteristic features extracted from the target images, successful pattern
      recognition with intraclass fault tolerance and interclass discrimination is
      achieved. A detailed system description is provided. Experimental demonstrations
      of a two-layer neural network for space-object discrimination is also presented.

PMID- 20820272
TI  - Optical implementations of radial basis classifiers.
AB  - We describe two optical systems based on the radial basis function approach to
      pattern classification. An optical-disk-based system for handwritten character
      recognition is demonstrated. The optical system computes the Euclidean distance
      between an unknown input and 650 stored patterns at a demonstrated rate of 26,000
      pattern comparisons/s. The ultimate performance of this system is limited by
      optical-disk resolution to 10(11) binary operations/s. An adaptive system is also
      presented -that facilitates on-line learning and provides additional robustness.

PMID- 20820273
TI  - Cascaded-grating holography for artificial neural networks.
AB  - A holographic technique for implementing optical neural networks is described in
      which each connection weight is distributed among a series of cascaded angularly
      and spatially multiplexed photorefractive gratings. This greatly reduces cross
      talk caused by the conical Bragg degeneracy associated with a single grating,
      reduces distortions caused by beam coupling, and improves the utilization of
      pixels in the input spatial light modulator. Experimental examples of high
      quality holographic storage and optical implementations of the perceptron and
      backpropagation neural networks are also discussed.

PMID- 20820274
TI  - Photorefractive adaptive resonance neural network.
AB  - We describe a novel adaptive resonance theory (ART) device that is fully optical
      in the input-output processing path. This device is based on holographic
      information processing in a photorefractive crystal. This sets up an associative
      pattern retrieval in a resonating loop that uses angle-multiplexed reference
      beams for pattern classification. A reset mechanism is used to reject any given
      beam, permitting an ART search strategy. The design is similar to an existing
      nonlearning optical associative memory, but ours permits learning and makes use
      of information that the other device discards. It is a suitable response to the
      challenges of connectivity, learning, and reset presented by ART architectures.
      Furthermore, the design includes an efficient mechanism for area normalization of
      templates. It also permits the user to capitalize on the ability of ART networks
      to process large patterns. This new device is expected to offer higher
      information storage density than alternative ART implementations.

PMID- 20820275
TI  - Optical competitive learning with, VLSI/liquid-crystal winner-take-all
      modulators.
AB  - A new approach to self-aligning unsupervised optical learning based on the
      competitive learning algorithm and adaptive holographic interconnections is
      introduced. A volume hologram is used to diffract the light from an input spatial
      light modulator so that it focuses upon a custom winner-take-all very-large-scale
      integrated circuit liquid-crystal spatial light modulator. The units that receive
      the most light switch to a reflective state, and the light reflected from the
      winning pixels interferes in the volume of the dynamic hologram with the phase
      conjugate of the input pattern in order to add an outer-product perturbation to
      the current holographic interconnection. As a set of input patterns is cycled
      through many times, the system learns to diffract the light from a particular
      input class upon a self-organized set of detectors that recognize similar input
      patterns without the aid of a teacher or any required alignment. Beam-propagation
      simulations are used to show that the holographic optical learning network
      faithfully reproduces the behavior of the ideal competitive learning algorithm. A
      winner-takeall detector/modulator device containing a total of 576 optical
      neurons grouped into 31 separate competitive patches in the required sparse-grid
      topology has been successfully fabricated, and experimental results are
      presented.

PMID- 20820276
TI  - Cross-talk noise in photorefractive interconnection.
AB  - The cross-talk noise in reconfigurable interconnection, which results from the
      nonuniform amplification in photorefractive two-wave mixing in the Fourier
      domain, in which maximum energy efficiency can be achieved, is considered. Both
      theoretical and experimental results are presented and discussed.

PMID- 20820277
TI  - Analysis of weighted fan-out/fan-in volume holographic optical interconnections.
AB  - The feasibility of employing volume holographic techniques for the implementation
      of highly multiplexed weighted fan-out/fan-in interconnections is analyzed on the
      basis of interconnection fidelity, optical throughput, and complexity of
      recording schedule or implementation hardware. These feasibility criteria were
      quantitatively evaluated using the optical beam propagation method to numerically
      simulate the diffraction characteristics of volume holographic interconnections
      recorded in a linear holographic material. We find that conventional
      interconnection architectures (that are based on a single coherent optical
      source) exhibit a direct trade-off between interconnection fidelity and optical
      throughput on the one hand, and recording schedule or hardware complexity on the
      other. In order to circumvent this trade-off we describe and analyze in detail an
      incoherent/coherent double angularly multiplexed interconnection architecture
      that is based on the use of multiple-source array of individually coherent but
      mutually incoherent sources. This architecture either minimizes or avoids several
      key sources of cross talk, permits simultaneous recording of interconnection
      weights or weight updates, and provides enhanced fidelity, interchannel
      isolation, and throughput performance.

PMID- 20820278
TI  - Real-time coherent image differentiation using a self-pumped phase conjugator
      with Cu:KNSBN.
AB  - A technique for real-time coherent image differentiation is described in a device
      consisting of a self-pumped phase conjugator that uses a copper-doped potassium
      sodium strontium barium niobate crystal. We demonstrate the proposed technique.

PMID- 20820280
TI  - Nasa patter.

PMID- 20820279
TI  - Optoelectronic implementation of a compression-attraction-sphere associative
      memory using an optical spatial pattern-encoding method.
AB  - A compression-attraction-sphere associative-memory model is proposed. An
      optoelectronic implementation of its inner-product architecture using an optical
      spatial pattern-encoding method is demonstrated bycomputer simulations and
      preliminary experiments.

PMID- 20820281
TI  - Modeling of the gain distribution for diode pumping of a solid-state laser rod
      with nonimaging optics.
AB  - We investigate the absorption distribution in a cylindrical gain medium that is
      pumped by a source of distributed laser diodes by means of a pump cavity
      developed from the edge-ray principle of nonimaging optics. The performance of
      this pumping arrangement is studied by using a nonsequential, numerical, three
      dimensional ray-tracing scheme. A figure of merit is defined for the pump
      cavities that takes into account the coupling efficiency and uniformity of the
      absorption distribution. It is found that the nonimaging pump cavity maintains a
      high coupling efficiency with extended two-dimensional diode arrays and obtains a
      fairly uniform absorption distribution. The nonimaging cavity is compared with
      two other designs: a close-coupled side-pumped cavity and an imaging design in
      the form of a elliptical cavity. The nonimaging cavity has a better figure of
      merit per diode than these two designs. It also permits the use of an extended,
      sparse, two-dimensional diode array, which reduces thermal loading of the source
      and eliminates all cavity optics other than the main reflector.

PMID- 20820282
TI  - Damage thresholds of (ZrO(2)-Y(2)O(3)/SiO(2) reflectors used for XeCl lasers.
AB  - An excimer laser reflector at the wavelength of 308 nm (XeCl) consisting of
      materials of ZrO(2)-Y(2)O(3) and SiO(2) is prepared. The reflectance reaches
      ~99.5% and the laser-induced damage threshold is raised to ~8.5 J/cm(2). The
      ZrO(2)-Y(2)O(3) mixture is proven to be a film material with a high laser damage
      resistance.

PMID- 20820283
TI  - Performance model for optical extraction from a Q-switched chemical oxygen-iodine
      laser.
AB  - A comprehensive time-dependent model for optical extraction from a Q-switched
      supersonic oxygen-iodine laser is described. Gas flow is treated by using an
      unsteady, premixed, quasi-one-dimensional model that accounts for gas motion and
      expansion as well as heat release in the cavity. The model uses a simplified,
      temperature-dependent, chemical kinetics package that consists of several
      reactions among the (3)Sigma, (1)Delta, and (1)Sigma states of oxygen, atomic and
      molecular iodine, water, and helium. Hyperfine relaxation effects on the gain and
      optical extraction from the 3 ? 4 line are treated by using a simple four-level
      laser model. An efficient algorithm for solving the coupled medium and optical
      extraction equations is described. This gain model, in conjunction with a
      geometric model of an unstable confocal resonator, is used to examine optical
      extraction from the medium as a function of pulse repetition rate, duty cycle,
      and optical mode width. It is shown that the output power may exhibit flow
      induced relaxation oscillat ons, and the conditions under which these
      oscillations occur are discussed.

PMID- 20820284
TI  - Single-frequency, 500-ns laser pulses generated by a passively Q-switched Nd
      laser.
AB  - We demonstrate a simple, passive technique for producing 500-ns pulse lengths
      with a Nd laser. The measured 1.5-MHz upper limit to the pulse spectral width
      indicates that it is nearly transform limited.

PMID- 20820285
TI  - Self-mixing interference in a diode laser: experimental observations and
      theoretical analysis.
AB  - The experimental results of an investigation of self-mixing effects or
      backscatter modulation in diode lasers coupled with a simple theoretical analysis
      are presented. The laser is used to send light, either in free space or through
      an optical fiber, to a movable target from which the optical backscatter is
      detected and fed back into the laser. In the experiment three significant
      conclusions are drawn: (1) self-mixing interference is not dependent on the
      coherence length of the laser, (2) the interference is not dependent on the use
      of a single-mode or multimode laser as the source, and (3) the interference is
      independent of the type of fiber employed, i.e., whether it is single mode or
      multimode. A comparison of this kind of interference with that in a conventional
      interferometer shows that self-mixing interference has the same phase sensitivity
      as that of the conventional arrangement, the modulation depth of the interference
      is comparable with that of a conventional interferometer, and the direction of
      the phase movement can be obtained from the interference signal. The above
      factors have implications for the optical sensing of a wide range of physical
      parameters. Several applications of the method are discussed that highlight the
      significant advantages of simplicity, compactness, and robustness as well as the
      self-aligning and self-detecting abilities of fiber-based self-mixing
      interferometry when compared with the use of conventional interference methods.

PMID- 20820286
TI  - Two-wave mixing of time-varying non-plane-wave optical fields in photorefractive
      materials.
AB  - A theoretical analysis is presented of two-wave mixing in photorefractive
      materials in which the complex amplitude of a weak signal beam has slowly varying
      but otherwise arbitrary spatial dependence and arbitrary time variation. The set
      of coupled partial differential equations that couple the dynamics of the optical
      fields to the photorefractive medium is solved analytically to give the complex
      amplitude of the transmitted signal in the undepleted pump regime. The results
      are compared with known results for the transient two-wave mixing of plane waves.

PMID- 20820287
TI  - Effect of the nonlinear stress-strain relationship on the maximum stress in
      silica fibers subjected to two-point bending.
AB  - We evaluate the effect of the nonlinear stress-strain relationship on the maximum
      curvature and maximum stress in silica fibers subjected to two-point bending. The
      analysis uses an assumption that this relationship, obtained experimentally for
      the case of uniaxial tension is also valid in the case of compression and is
      applicable to bending deformations as well. We show that the shift in the neutral
      axis due to the nonlinear stress-strain relationship has an appreciable effect on
      the maximum stress, while its effect on the maximum curvature is small and need
      not be considered. We show also that this relationship, obtained for strains not
      exceeding 5% cannot be applied for very large strains. Therefore we conclude that
      the future experimental work should include the evaluation of the nonlinear
      behavior of the material, both in tension and compression, for higher strains and
      for high strength fibers. The obtained results can be helpful in the analysis of
      optical silica fibers experiencing two-point bending.

PMID- 20820288
TI  - Coupling-sensitivity comparison of hemispheric and hyperbolic microlenses.
AB  - We investigate the effects of translational displacements and angular
      misalignments of semiconductor laser-fiber systems coupled to tapered,
      hemispheric and laser-machined, hyperbolic microlenses. Hyperbolic lenses, which
      typically couple 2 dB more optical power into a single-mode fiber than do
      hemispheric lenses, are more sensitive to translational offsets, although they
      are less sensitive to angular misalignments. We demonstrate that increased
      coupling can be permanently realized in a system through the use of the
      hyperbolic lens if the laser package can confine the position of the lens to
      within a 1.6-microm region. Angular misalignments can be as large as 10 degrees
      for a 0.5-dB power penalty for the hyperbolic microlens.

PMID- 20820289
TI  - Time-delay Fizeau phase-conjugate interferometer.
AB  - A time-delay Fizeau phase-conjugate interferometer is constructed by using a
      BaTiO(3) crystal in a degenerate four-wave-mixing configuration. The slow
      response time of BaTiO(3) is used to build a phase-conjugate mirror that
      functions as a holographic memory. An optical wave and its time-delayed version
      are stored inside the crystal sequentially while their phase-conjugate waves are
      generated simultaneously. Superposition of the two phase-conjugate waves produces
      an interferogram as a result of the relative phase change of the input waves. The
      simplicity and real-time operation of this technique lead to several advantages
      over the conventional holographic interferometry. The use of photorefractive
      crystal eliminates the darkroom process and reposition procedure. A higher
      accuracy can be achieved because the interfering waves are phase-conjugate waves.
      The principle of this technique is presented and the experimental results and its
      applications are discussed.

PMID- 20820290
TI  - Efficient polarization analyzer for Lyman(alpha) radiation.
AB  - A new efficient polarization analyzer for Lyman(alpha) radiation is described and
      compared with previously reported instruments.

PMID- 20820291
TI  - Laboratory simulations of lidar returns from clouds: experimental and numerical
      results.
AB  - The experimental results of laboratory simulations of lidar returns from clouds
      are presented. Measurements were carried out on laboratory-scaled cloud models by
      using a picosecond laser and a streak-camera system. The turbid structures
      simulating clouds were suspensions of polystyrene spheres in water. The
      geometrical situation was similar to that of an actual lidar sounding a cloud
      1000 m distant and with a thickness of 300 m. Measurements were repeated for
      different concentrations and different sizes of spheres. The results show how the
      effect of multiple scattering depends on the scattering coefficient and on the
      phase function of the diffusers. The depolarization introduced by multiple
      scattering was also investigated. The results were also compared with numerical
      results obtained by Monte Carlo simulations. Substantially good agreement between
      numerical and experimental results was found. The measurements showed the
      adequacy of modern electro-optical systems to study the features of multiple
      scattering effects on lidar echoes from atmosphere or ocean by means of
      experiments on well-controlled laboratory-scaled models. This adequacy provides
      the possibility of studying the influence of different effects in the laboratory
      in well-controlled situations.

PMID- 20820292
TI  - Wavelength dependence of backscattering and extinction of kaolin dust at CO(2)
      laser wavelengths: effect of multiple scattering.
AB  - A multiple wavelength, pulsed CO(2) lidar system is used to measure spectral
      backscattering and extinction of kaolin dust of different optical thicknesses.
      The measurements show that the wavelength dependence of spectral backscattering
      changes with increased multiple scattering, whereas the spectral extinction
      remains relatively unchanged. A simple analytical two-stream radiative transfer
      model is used to confirm the measurements qualitatively. Several equations were
      derived from the model to show that in general the wavelength dependence of
      backscatter is less dependent on wavelength for a multiplescattering case.
      Therefore, the aerosol cloud becomes a diffuse target that is more flat in its
      spectral reflectance as multiple scattering increases. An application to
      differential absorption detection is discussed and shows that, in general, the
      effect of multiple scattering on the backscattered signal from aerosols will tend
      to reduce the error in deducing the average path-length concentration of the
      absorbing tr ce gas.

PMID- 20820293
TI  - Radiative transfer in the ocean: computations relating to the asymptotic and near
      asymptotic daylight field.
AB  - The asymptotic daylight field in a homogeneous ocean is, like the absorption (a),
      scattering (b), and attenuation (c) coefficients and the volume scattering
      function (VSF), an inherent optical property (IOP) of the medium. A simple
      relationship in the spirit of the van de Hulst similarity relationships is
      developed from which the diffuse attenuation coefficient K(infinity) of the
      asymptotic light field can be obtained from a, b, and the VSF with an error of <
      2%. In this relationship, the shape of the VSF is characterized by its asymmetry
      parameter g, whereas omega(0) = b/c characterizes the other IOP's. The
      relationship applies approximately to other quantities as well, particularly
      tau(x), which is the optical depth at which the downwelling irradiance
      attenuation coefficient K(d) can be replaced by K(infinity) with an error no
      greater than x%. Computations of tau(5) and tau(10) are presented as a function
      of g, omega(0) and the incident light field, and it is shown that for overcast
      conditions K(d) can be within 5% of K(infinity) at depths at which the
      downwelling irradiance is greater than 50% of its value at the surface.
      Simulations of radiative transfer in verticall inhomogeneous waters reveal that
      for sufficiently large depth (z), the value of K(infinity)(z) determined from the
      asymptotic theory that uses the values of the IOP's at z is a good approximation
      to K(d)(z). Thus our results suggest that in addition to being a pedagogically
      interesting concept, the asymptotic theory may actually be useful in ocean optics
      research. The influence of inelastic processes (fluorescence and Raman
      scattering) on K(infinity) are briefly examined, and it is shown that for an
      ocean of pure sea water, i.e., no particles or fluorescent compounds,
      K(infinity)(lambda) approximately 0.02 m(-1) for lambda >/= 430 nm with little
      spectral variation.

PMID- 20820294
TI  - Comparison of radiances observed from satellite and aircraft with calculations by
      using two atmospheric transmittance models.
AB  - An evaluation of two different atmospheric transmittance models is performed by
      using radiance data from the high-resolution infraRed Sounder (HIRS) instrument
      onboard the National Oceanic and Atmospheric Administration's NOAA-9 satellite
      and the airborne high-resolution interferometer sounder (HIS) instrument.
      Synthetic radiances have been derived from collocated radiosondes by using the
      television infrared observation satellite (TIROS) operational vertical sounder
      (TOVS) operational transmittance model and the fast atmospheric signature code
      (FASCOD2) line-by-line transmittance model for comparison with the two
      independent instrument observations. Radiance observations in various spectral
      channels from the HIRS and HIS instruments along with the synthetic radiances
      derived from the FASCOD2 and operational TOVS transmittance models are used for
      the performance evaluation. The results of the comparison reveal a significant
      discrepancy between 707 and 717 cm(-l) in the radiance calculation for both
      models. Exce llent agreement is observed between observation and calculation for
      the lower tropospheric long-wave temperature sounding channels. Serious problems
      are noted with the modeling of water vapor in the operational TOVS transmittance
      model. In addition, poor performance by FASCOD2 is revealed for the short
      wavelength N(2)O-CO(2) HIRS spectral channels. In general the operational TOVS
      transmittance model is found to be only slightly inferior to the FASCOD2 model.
      Regarding the performance of the instruments, observations from the NOAA-9 HIRS
      and the aircraft HIS are comparable in terms of their agreement with theoretical
      computations.

PMID- 20820295
TI  - Scattering of an evanescent surface wave by a microscopic dielectric sphere.
AB  - A ray-optics scattering model has been developed to determine if multiple
      reflections between the sphere and the plate could alter the exponential
      relationship between the scattering intensity and the separation distance as
      contact is approached. Results indicate that the effect of multiple reflections
      is dependent on sphere size, refractive indices, and the penetration depth of the
      evanescent wave. An experimental validation of the model was performed with
      polystyrene spheres (diameters 7-30 microm) immersed in an alcohol mixture and
      resting on an MgF(2) film that had the same refractive index. Film thicknesses
      varied between 0 and 300 nm. No significant effect of multiple reflections was
      measured at an incident angle approximately 2 degrees above the critical angle,
      which was in agreement with the predictions of the ray-optics model. By contrast,
      the scattering intensity from a 300-microm sphere was predicted to be much more
      sensitive to the separation distance at separations below one penetration depth
      when the incident a ngle was increased to over 6 degrees above the critical
      angle.

PMID- 20820296
TI  - Extraction of bimodal aerosol-size distribution radii from spectral and angular
      slope (Angstrom) coefficients.
AB  - A methodology is defined whereby the effective aerosol bimodal radii of the fine
      (accumulation) mode and the coarse (supermicron) mode can be directly and simply
      extracted from slope (Angstrom) coefficients derived from ground-based solar
      spectral transmission data and aureole scattering data.

PMID- 20820297
TI  - Constraints on Mueller matrices of polarization optics.
AB  - The issue of physical realizability constraints on depolarizing scattering or
      imaging systems is addressed. In particular, the overpolarization problem, i.e.,
      the problem of ensuring that the output degree of polarization is always smaller
      than (or equal to) unity, is discussed in detail. A set of necessary conditions
      for the elements of a Mueller matrix is derived. These conditions can be used to
      test the accuracy of polarimetric measurements and computations. Several recent
      experimental examples from polarization optics and radar are discussed.

PMID- 20820298
TI  - Optical wave propagation in discrete random media with large particles: a
      treatment of the phase function.
AB  - A treatment of the phase function in the radiative transfer equation is discussed
      for describing optical wave propagation in discrete random media with large
      particles. Unlike the conventional small-angle approximation, the phase function
      is normalized so that half of the scattered power is removed from a small angle
      in the forward direction for large particles with the refractive index not close
      to unity. With this normalization, an improved small-angle solution of the
      radiative transfer equation is given for the phase function adopted here. The
      validity of the proposed theory is confirmed by comparisons with both numerical
      solutions and experimental data on the attenuation of millimeter and optical
      waves in rain.

PMID- 20820299
TI  - Space optics: an introduction by the editors.
AB  - This feature of Applied Optics consists of papers on the Hubble Space Telescope
      and its instruments as well as other new instruments and other new optics
      technology for space science. Many of the papers are an outgrowth of the papers
      presented at the Second Space Optics Topical Meeting, October 1991, in
      Williamsburg, Va. This introduction provides an overview for the papers related
      to the Hubble Space Telescope: measurement of the error and approaches to correct
      for the error.

PMID- 20820300
TI  - On-orbit performance of the Hubble Space Telescope optical control system.
AB  - On-orbit data are used to examine the performance of the Hubble Space Telescope
      optical control system. The precision, relative accuracy, and absolute accuracy
      of the off-axis Wavefront-Sensor measurements are evaluated and compared with
      design requirements. The internal stability of the sensors is better than 0.006
      microm rms over five years, including launch. Random errors are estimated to be
      within 0.01 microm rms. Systematic errors are present in the estimates of focus,
      spherical, and coma aberrations, but none has been identified for astigmatism.
      Primary-mirror spherical aberration is believed to be the probable cause of all
      subspecification performances.

PMID- 20820301
TI  - On-orbit performance of the Hubble Space Telescope fine guidance sensors.
AB  - The observed and measured on-orbit performance of various aspects of the fine
      guidance sensors is presented and discussed in the light of the original
      requirements and predictions. The fine guidance sensors are shown to meet or
      exceed the original requirements concerning dynamic pointing errors, photometric
      repeatability, and moving-target tracking capability. Calibration accuracy has
      been sufficient for observations to date, and fine-lock acquisitions are
      approaching a 100% success rate. Improvements to the fine-guidance-sensor
      tolerance of telescope spherical aberration, the South Atlantic anomaly, and
      solar-panel vibrations have been made, and further improvements are expected.

PMID- 20820302
TI  - Hubble Space Telescope fine-guidance-sensor transfer function and its impact on
      telescope alignment and guidance.
AB  - We describe the use of Hubble Space Telescope Fine Guidance Sensor transfer scans
      to characterize telescope alignment. To accomplish this we developed a software
      system to extract the aberration content from the observed transfer scans. The
      transfer scans show large aberration levels that do not originate in the
      telescope. The appearance of significant coma in the transfer scans has been
      identified as resulting from the shearing of spherical aberration caused by a
      beam misalignment within the Fine Guidance Sensors themselves.

PMID- 20820303
TI  - Hubble Space Telescope primary-mirror characterization by measurement of the
      reflective null corrector.
AB  - The reflective null corrector used to manufacture of the Hubble Space Telescope
      contains valuable information about the prescription of the primary mirror since
      an excellent null was achieved between the null-corrector wave front and the
      primary-mirror wave front. During the Phase I measurements, the leading cause of
      the spherical aberration, the field lens position error, was discovered and
      remeasured to an accuracy of +/-0.005 mm. To derive the conic constant of the
      primary mirror to an accuracy of +/-0.0003, we remeasured the parameters of the
      reflective null corrector that could contribute to the spherical aberration of
      the primary mirror.

PMID- 20820304
TI  - Determination of the Hubble Space Telescope effective conic-constant error from
      direct image measurements.
AB  - Direct measurement of discernible features in the Hubble Space Telescope (HST)
      imagery has enabled a self-consistent determination to be made of the effective
      conic constant of HST images taken with planetary camera 6 (PC-6) of the wide
      field and planetary camera. Before being corrected for the contribution from PC
      6, the conic constant is - 1.01429 +/- 0.0002. The correction for PC-6 is less
      accurately determined but probably lies between -0.0002 and 0.0004. As a result
      the HST optics are characterized best by a conic constant of - 1.0140 +/- 0.0003
      as obtained from direct image measurements.

PMID- 20820305
TI  - Artificial neural network for the determination of Hubble Space Telescope
      aberration from stellar images.
AB  - An artificial-neural-network method, first developed for the measurement and
      control of atmospheric phase distortion, using stellar images, was used to
      estimate the optical aberration of the Hubble Space Telescope. A total of 26
      estimates of distortion was obtained from 23 stellar images acquired at several
      secondary-mirror axial positions. The results were expressed as coefficients of
      eight orthogonal Zernike polynomials: focus through third-order spherical. For
      all modes other than spherical the measured aberration was small. The average
      spherical aberration of the estimates was -0.299 microm rms, which is in good
      agreement with predictions obtained when iterative phase-retrieval algorithms
      were used.

PMID- 20820306
TI  - Hubble Space Telescope prescription retrieval.
AB  - Prescription retrieval is a technique for directly estimating optical
      prescription parameters from images. We apply it to estimate the value of the
      Hubble Space Telescope primary mirror conic constant. Our results agree with
      other studies that examined primary-mirror test fixtures and results. In addition
      they show that small aberrations exist on the planetary-camera repeater optics.

PMID- 20820307
TI  - Phase-retrieval algorithms for a complicated optical system.
AB  - Phase-retrieval algorithms have been developed that handle a complicated optical
      system that requires multiple Fresnellike transforms to propagate from one end of
      the system to the other including the absorption by apertures in more than one
      plane and allowance for bad detector pixels. Gradientsearch algorithms and
      generalizations of the iterative-transform phase-retrieval algorithms are
      derived. Analytic expressions for the gradient of an error metric, with respect
      to polynomial coefficients and with respect to point-by-point phase descriptions,
      are given. The entire gradient can be computed with the number of transforms
      required to propagate a wave front from one end of the optical system to the
      other and back again, independent of the number of coefficients or phase points.
      This greatly speeds the computation. The reconstruction of pupil amplitude is
      also given. A convergence proof of the generalized iterative transform algorithm
      is given. These improved algorithms permit a more accurate characterizationof
      complicated optical systems from their point spread functions.

PMID- 20820308
TI  - Hubble Space Telescope characterized by using phase-retrieval algorithms.
AB  - We describe several results characterizing the Hubble Space Telescope from
      measured point spread functions by using phase-retrieval algorithms. The Cramer
      Rao lower bounds show that point spread functions taken well out of focus result
      in smaller errors when aberrations are estimated and that, for those images,
      photon noise is not a limiting factor. Reconstruction experiments with both
      simulated and real data show that the calculation of wave-front propagation by
      the retrieval algorithms must be performed with a multiple-plane propagation
      rather than a simple fast Fourier transform to ensure the high accuracy required.
      Pupil reconstruction was performed and indicates a misalignment of the optical
      axis of a camera relay telescope relative to the main telescope. After we
      accounted for measured spherical aberration in the relay telescope, our estimate
      of the conic constant of the primary mirror of the HST was - 1.0144.

PMID- 20820309
TI  - Reflective correctors for the Hubble Space Telescope axial instruments.
AB  - Reflective correctors to compensate the spherical aberration in the Hubble Space
      Telescope are placed in front of three of the axial scientific instruments (a
      camera and two spectrographs) during the first scheduled refurbishment mission.
      The five correctors required are deployed from a new module that replaces the
      fourth axial instrument. Each corrector consists of a field mirror and an
      aspherical, aberration-correcting reimaging mirror. In the camera the angular
      resolution capability is restored, be it in reduced fields, and in the
      spectrographs the potential for observations in crowded areas is regained along
      with effective light collection at the slits.

PMID- 20820310
TI  - Telescope simulators for Hubble: an overview of optical designs.
AB  - Various optical configurations for Hubble Space Telescope simulators have been
      proposed, and some are being built for use as verification tools to characterize
      the performance of second-generation instruments during ground testing. We
      describe the Hubble Space Telescope, present an overview of three optical designs
      for simulators, and discuss the relative advantages and disadvantages of each
      configuration.

PMID- 20820311
TI  - Optical design of zero-power Hubble Space Telescope wave-front correctors for
      null testing.
AB  - The optical design of the second-generation wide-field/planetary-camera
      instrument for the Hubble Space Telescope has been modified to compensate for the
      spherical aberration of the optical telescope assembly (OTA) by introduction of
      undercorrected spherical aberration into the wave front. This instrument can be
      tested in a simple manner to ensure that its aberration contribution has the
      proper sign and magnitude. We present designs for a near-zero power doublet lens
      that can be used to generate a spherically aberrated wave front that is similar
      to the OTA wave front. When this lens is used in combination with the instrument,
      a near-perfect or nulled wave front should be produced, resulting in a high
      quality point image on axis. We also present lens designs for a similar test that
      can be performed on the OTA simulators now being built to verify the other second
      generation instruments.

PMID- 20820312
TI  - Hubble Space Telescope COSTAR asphere verification with a modified computer
      generated hologram interferometer.
AB  - To correct for the spherical aberration in the Hubble Space Telescope primary
      mirror, five anamorphic aspheric mirrors representing correction for three
      scientific instruments have been fabricated as part of the development of the
      corrective-optics space telescope axial-replacement instrument (COSTAR). During
      the acceptance tests of these mirrors at the vendor, a quick and simple method
      for verifying the asphere surface figure was developed. The technique has been
      used on three of the aspheres relating to the three instrument prescriptions.
      Results indicate that the three aspheres are correct to the limited accuracy
      expected of this test.

PMID- 20820313
TI  - Orbiting stellar interferometer for astrometry and imaging.
AB  - <p>The orbiting stellar interferometer (OSI) is a concept for a first-generation
      space interferometer with astrometric and imaging goals and is responsive to the
      recommendations of the Astronomy and Astrophysics Survey Committee for an
      astrometric interferometer mission. The OSI, as developed at the Jet Propulsion
      Laboratory over the past several years, is a triple Michelson interferometer with
      articulating siderostats and optical delay lines. Two point designs for the
      instrument are described.</p><p>The 18-m design uses an 18-m maximum baseline and
      aperture diameters of 40 cm; the targeted astrometric performance is a wide-field
      accuracy of 10 microarsec for 16-mag objects in 100 s of integration time and for
      20-mag objects in 1 h. The instrument would also be capable of synthesis imaging
      with a resolution of 5 marcsec, which corresponds to the diffraction limit of the
      18-m base line. The design uses a deployed structure, which would fold to fit
      into an Atlas HAS shroud, for insertion into a 900-km sun-synchronous orbit In
      addition to the 18-m point design a 7-m point design that uses a shorter base
      line in order to simplify deployment is also discussed. OSI's high performance is
      made possible by utilizing laser metrology and controlled-optics technology.</p>

PMID- 20820314
TI  - Long-duration orbital effects on optical coating materials.
AB  - We flew specimens of eight different optical coating materials in low earth orbit
      as part of the Long Duration Exposure Facility manifest to determine their
      ability to withstand exposure to the residual atomic O and other environmental
      effects at those altitudes. We included samples of Al, Au, Ir, Os, Pt, Al +
      MgF(2), Al + SiO(x), and chemical-vapor-deposited SiC, representing reflective
      optical applications from the vacuum ultraviolet through the visible portions of
      the spectrum. We found that the majority of the materials suffered sufficient
      reflectance degradation to warrant careful consideration in the design of future
      space-flight instrumentation.

PMID- 20820315
TI  - Effect of oxygen atom bombardment on the reflectance of silicon carbide mirrors
      in the extreme ultraviolet region.
AB  - Chemical-vapor-deposited silicon carbide mirrors were exposed to bombardment by 8
      km/s oxygen atoms that simulated the effects of exposure in low Earth orbit for
      periods up to 7.5 yr. The reflectances of four mirrors were measured before and
      after exposure at five wavelengths (58.4, 73.6, 104.8, 121.6, and 161 nm) and at
      11 angles of incidence from 5 degrees to 80 degrees . The oxygen exposure reduced
      the normal-incidence reflectances by factors of 1.5-4.5 in the wavelength rate of
      58.4-121.6 nm but had no effect on the visual appearance. The optical constants
      and the thicknesses of the thin surface layers present on the SiC substrates were
      determined from the reflectance measurements. This analysis indicated that before
      exposure the surface layers were composed of SiO(x) (where x is ~ 1.5) with
      thicknesses of 0.8-1.8 nm. After exposure to 8-km/s oxygen atoms, the surface
      layers were composed of SiO(x) with thicknesses of 3.5-4.5 nm. There were no
      systematic differences between the measured reflectances after simulated space ex
      osures of 1.5, 4.5, and 7.5 years. This implied that most of the growth in
      thickness of the SiO(x). layers occurred early in the exposure and stabilized at
      thicknesses of 3.5-4.5 nm. The optical results were consistent with x-ray
      photoelectron spectroscopy of the four mirrors after oxygen exposure.

PMID- 20820316
TI  - Thermal stability of soft x-ray Mo-Si and MoSi(2)-Si multilayer mirrors.
AB  - The thermal stability of Mo-Si multilayers prepared by magnetron sputtering is
      studied. It is found that degradation of x-ray reflectivity of Mo-Si multilayers
      under heat loading is connected with the roughening of Mo-Si interfaces and the
      formation of compounds Mo(x)Si(y),. To avoid these degradation mechanisms we
      fabricated and tested MoSi(2)-Si multilayers under heat loading. The MoSi(2)-Si
      multilayer appeared to be much more stable both in period and x-ray reflectivity
      because of thermodynamic equilibrium of the components MoSi(2) and Si at the
      interface. The working temperature of MoSi(2)-Si multilayers reaches 1000 K.

PMID- 20820317
TI  - Digital speckle-displacement measurement using a complex spectrum method.
AB  - An alternative approach to fully automatic speckle-displacement measurement is
      described. Two speckle patterns of a specimen, one before and one after
      deformation, are captured by a CCD camera and registered by a frame grabber. Two
      series of small subimages are obtained by segmenting the two speckle patterns.
      The corresponding subimage pairs extracted from both series are analyzed
      pointwise. The interrogation of each subimage pair involves a two-step fast
      Fourier transform. While the first-step fast-Fourier transform achieves a complex
      spectrum characterized by the local displacement information, the second-step one
      generates a signal peak in the second spectral domain that resolves the local
      displacement vector. A rough estimate of the displacement vector is achieved by
      detecting the maximum pixel of the discrete spectrum. A more accurate
      determination is attained by a subpixel-maximum determination through a
      biparabolic fitting near the signal peak. The u- and v-displacement fields are
      deduced by analyzing all subimage pairs. A large rigid-body displacement can be
      overcome by introducing an artificial rigid shift of the two speckle patterns
      toward each other before the numerical process. The technique retains all the
      advantages of optical speckle photography and provides an extended range of
      measurement. Dynamic incremental deformations can be inspected by registering
      more speckle patterns at many consecutive deformation stages by using a high
      speed CCD camera. The system was applied successfully to the study of crack-tip
      deformation fields.

PMID- 20820318
TI  - Design of a symmetric self-electro-optic-effect-device cellular-logic image
      processor.
AB  - A cellular-logic image processor was designed, constructed, and successfully
      operated by interconnecting two arrays of 128 symmetric self-electro-optic-effect
      devices. Design issues associated with the implementation of this free-space
      digital-optical system are discussed.

PMID- 20820319
TI  - Parallel electro-optical rule-based system for fast execution of expert systems.
AB  - The slow execution speed of current rule-based systems has restricted their
      application areas. Multiprocessor architectures have been proposed to overcome
      this limitation. However, as the number of processors in a multiprocessor system
      grows, so does the cost of communication between processors or between processor
      and memory units. The use of optics for a fast and parallel implementation of
      rule-based systems is proposed. The proposed optical system is hybrid in nature,
      using electronics for the user interface and optics for the rule-based inference
      engine. The proposed system uses twodimensional planes as basic computational
      entities and is therefore able to provide concurrent rule processing.
      Furthermore, it provides highly efficient implementation of the basic operations
      needed in rule-based systems; namely, matching, selection, and rule firing. The
      execution speed of the proposed system is theoretically estimated and is shown to
      be potentially of orders of magnitude faster than current electronic system.

PMID- 20820320
TI  - Visual cortex operations and their implementation using the incoherent optical
      neuron model.
AB  - The incoherent optical neuron model uses two different device responses, an
      inhibitory response and a nonlinear output response, to realize a complete neuron
      unit that has both inhibitory and excitatory inputs. We describe its use to
      implement a model of simple cells of the visual cortex. Such simple cells perform
      the operations of edge detection, orientation selection, and in the case of
      moving objects, direction and speed selection. Experiments are described that
      utilize two Hughes liquid-crystal light valves to perform the functions of input
      transduction and optical neuron unit-array implementation. A multiplexed
      dichromated gelatin hologram serves as a holographic optical element that forms
      space-invariant (but otherwise arbitrary) point-spread functions for the network
      interconnections. Changing the holographic interconnection pattern permits
      implementation of different simple cells performing, e.g., transient response,
      edge detection, orientation preference, and direction and speed preference.
      Experimental results of these operations are presented.

PMID- 20820321
TI  - Photoanisotropic incoherent-to-coherent optical conversion.
AB  - A new approach to incoherent-to-coherent optical conversion based on a real-time
      five-wave-mixing technique in photoanisotropic organic film is presented. A
      uniform grating is written holographically in the sample and then erased locally
      by an incident white-light image. Subsequent coherent diffraction of the
      spatially modulated grating imposes the incoherent image upon the reading laser
      beam, permitting subsequent coherent optical processing. A theoretical analysis
      of the holographic recording and erasing mechanism in these photoanisotropic
      materials is presented, and the saturation is shown to be responsible for the
      grating intermodulation that produces the incoherent-to-coherent conversion.
      Experimental results of white-light images converted to inverted coherent images
      in real time are presented, and the resolution is shown to exceed 28 line
      pairs/mm.

PMID- 20820322
TI  - Polarization- and thickness-dependent near fields of small phase-shifting
      structures.
AB  - The spatial distribution of amplitude and phase in the diffraction near field
      behind phase-shifting structures of infinite length and small rectangular cross
      section (</= lambda(2), lambda is the wavelength) is investigated for incident,
      linearly polarized plane waves. The near fields are computed by an inverse
      Fourier transformation of the calculated angular spectra; 3-cm microwave
      measurements yield good agreement. The computed near fields are compared to the
      structure images in the range of geometrical optics. Quantitative relations are
      derived for the deviations between the corresponding angular spectra, depending
      on polarization of the incident wave and structure thickness.

PMID- 20820323
TI  - Technique for reducing the redundant and self-correlation terms in joint
      transform correlators.
AB  - We describe a joint transform correlator in which the reference signal and the
      input scene are placed in different input planes along the optical axis. We show
      that this system focuses the off-axis crosscorrelation functions and the on-axis
      autocorrelation functions in different output planes. In a conventional joint
      transform correlator these terms are produced in the same output plane. The
      effect of placing the input scene and the reference signal in different input
      planes is analyzed mathematically. Computer simulations and experimental results
      are presented to illustrate the performance of this correlator. We show that for
      the nonlinear joint transform correlator the higher-order correlation terms are
      produced in different output planes.

PMID- 20820324
TI  - Multiple-object input in nonlinear correlation.
AB  - Multiple-object input to the recently introduced phase-extraction correlator may
      cause difficulties owing to interference effects. Similar effects have been
      observed previously in the nonlinear joint transform correlator. It is shown
      theoretically and by computer simulations that these effects are seldom
      observable in practice, and even then they can be substantially reduced by
      employing a proper space-variant threshold. The implementation of this scheme by
      a hybrid electro-optical architecture is also explained briefly and demonstrated.
      The results presented permit manipulation of information (spectral phase) that
      was previously believed to be contaminated beyond recovery.

PMID- 20820325
TI  - Optimality of trade-off filters.
AB  - We compare the optimal trade-off approach for synthetic discriminant function
      filters and an approach introduced recently, the minimum noise and correlation
      energy filter, using an objective quantitative figure of merit. A new general
      definition of multicriteria optimal trade-off correlation filters is introduced
      based on this comparison.

PMID- 20820326
TI  - Experimental demonstration of an acousto-optic system for two-dimensional phased
      array antenna scanning.
AB  - A novel in-line interferometric acousto-optic architecture for two-dimensional
      beam scanning of planar phased arrays is demonstrated experimentally for a 330
      MHz carrier. The required modulo-2pi phase control along the two orthogonal
      antenna-array directions is achieved by using two independent control frequencies
      f(1) and f(2) with frequency variations of 0-170 and 0-210 kHz, respectively. A
      processor output carrier signal-to-noise ratio of 48 dB at + 1-MHz offset is
      measured in an analyzer bandwidth of 300 kHz, with a carrier tuning range of 90
      MHz.

PMID- 20820327
TI  - Optical implementation of quadratic associative memory by use of persistent
      spectral hole-burning media.
AB  - Optical implementation of a three-dimensional associative-memory tensor with 32 x
      32 x 32 weighted interconnections between elements of the input and output
      vectors in quadratic associative memory is obtained by the use of persistent
      spectral hole-burning media. The capability of the present optical scheme for
      correcting errors in the intput image is demonstrated.

PMID- 20820328
TI  - Limits of scalar diffraction theory for conducting gratings.
AB  - Scalar diffraction theory and electromagnetic vector theory are compared by
      analyzing plane-wave scattering by a perfectly conducting, rectangular-grooved
      grating. General field solutions for arbitrary angles of incidence are derived by
      using scalar and vector theories. Diffraction efficiencies for the scalar and the
      vector cases as functions of wavelength, grating period, and angles of incidence
      are determined numerically and plotted. When the wavelength of the incident field
      is much shorter than the grating period, the diffraction efficiencies match. But
      when the wavelength is of the order of the grating period, large differences
      between the scalar and the vector solutions emerge. One general conclusion is
      that, depending on polarization, scalar theory should not be used when the
      grating period becomes smaller than ten wavelengths.

PMID- 20820329
TI  - Real-time image transmission and interferometry through a distorting medium using
      two phase conjugators.
AB  - A phase-conjugate geometry with two photorefractive crystals is demonstrated. It
      can be used for real-time one- or two-way image transmission through a distorting
      medium and for real-time holographic interferometry.

PMID- 20820330
TI  - Detection of optical signals with high-amplitude phase modulation by adaptive
      photodetectors.
AB  - Results of a detailed theoretical analysis on the detection of phase-modulated
      optical signals with an arbitrary modulation index (Delta >< 1) and modulation
      frequency (omega/omega(0) >< 1, where omega(0) is the characteristic cutoff
      frequency) by adaptive photodetectors that are based on photorefractive crystals
      and the nonsteady- state photo-electromotive force are presented. Besides general
      analytical results, numerical calculations of the output signal form and the
      amplitude and the phase of its first and second harmonics are given. The main
      predictions of the theoretical analysis are illustrated by the experimental data
      obtained for a high-sensitivity cubic photorefractive Bi(12)SiO(20) crystal at
      the wavelength (lambda = 488 nm) of an argon-ion laser.

PMID- 20820331
TI  - Signaling system for multiple-access laser communications and interference
      protection.
AB  - Signaling by spatial coding is proposed for asynchronous multiple-access free
      space optical communications and interference mitigation. The large spatial
      bandwidth (e.g., 10(6) pixels) of each laser transmitter aperture is utilized for
      user coding, while the transmitter temporal bandwidth is preserved for
      information signals. Signal recovery is based on incoherent optical detection,
      spatial sampling, and electronic or optical matched filtering of the remotely
      received transmit optical beam Fresnel or Fraunhofer diffraction pattern. The
      proposed signaling method is appropriate for multiple-access free-space laser
      links involving multiple transmitters that use a common receiver. With electronic
      filtering, low-to-medium (e.g., 3 Mbits/s) data-rate users are appropriate. With
      a lenslet-array-based incoherent optical correlator, higher (e.g., 100 Mbits/s)
      data rates can be achieved. Improved interference protection is achieved cby
      spatially distributed bit-duration-based processing. Preliminary simulation
      results are carried out to demonstrate operating principles.

PMID- 20820332
TI  - Distortion-free multiplexed holography in striated photorefractive media.
AB  - Growth-induced striations in photorefractive media constitute phase gratings that
      scatter transmitted light and therefore degrade the quality of reconstructed
      images in holographic applications. A simple angular multiplexed holographic
      memory arrangement in a striated strontium barium niobate sample is considered.
      For forward-propagating reconstruction the striations distort the readout images
      and introduce ghost images. For counterpropagating readout, inhomogeneous image
      reconstruction and interimage cross talk can occur. We investigate these effects
      experimentally for different reconstruction methods and demonstrate the cross
      talk and the ghost images with a simple model based on coupled-wave theory.
      Readout with a counterpropagating plane wave eliminates the ghost images and the
      distortions but suffers degradation from cross talk and inhomogeneous image
      intensity. Only reconstruction with a phase conjugate of the transmitted
      reference beam eliminates cross talk and distortions. The model indicates that
      negligible material dispersion is a necessary requirement for high-quality
      phaseconjugation readout.

PMID- 20820333
TI  - Real-time interferometry with photorefractive reference holograms.
AB  - Experimental results on real-time holographic interferometry using
      photorefractive iron-doped lithium niobate crystals to store the reference
      holograms are presented. Since the crystals are self-developing, precise
      repositioning of the reference hologram or in situ wet processing is not needed.
      With proper choice of experimental parameters it is found that the same reference
      hologram can be used for real-time processing of long sequences ( 10 min.) of
      input data with minimal degradation. The results obtained on visualization of
      heat-flow patterns from electronic chips illustrate the utility of this approach.

PMID- 20820334
TI  - Database management using optical array logic.
AB  - Database management is considered as an application of optical array logic. To
      generalize the problem, a systematic procedure for massively parallel data
      processing that consists of pattern expansion, template matching, magnitude
      comparison, and sorting is presented. With this procedure, a method for
      implementing basic operations for relational database models is developed. Basic
      operations are described by parallel programs in optical array logic. Developed
      programs are evaluated by their performance. To improve the performance, the
      development of specialized optical functional modules is needed.

PMID- 20820335
TI  - Penta prism laser polarizer.
AB  - A novel type of laser prism polarizer is proposed. The polarizer is characterized
      by a high transmission efficiency, a high optical damage threshold, and a high
      extinction ratio. The polarizer is shaped like a regular penta prism and, thus,
      it is a constant deviation angle device. Polarization effects occur upon the two
      internal cascade reflections in the prism. Anisotropic and Isotropic types of the
      polarizer are discussed. The isotropic polarizer is a prism made of a high
      refractive-index glass coated by multilayer polarization-type dielectric
      coatings. Efficient s-state polarization is obtained because of p-state leakage
      upon the two internal cascade reflections. The anisotropic polarizer is made of a
      birefringent crystal in which angular polarization splitting is obtained by the
      bireflectance (double-reflection) effect. Fanning of a laser beam into up to
      eight polarized beams is possible in a prism made of a biaxial crystal.

PMID- 20820336
TI  - Polarized spectral emittance from periodic micromachined surfaces: V. Undoped
      silicon: angular measurement in shallow lamellar gratings.
AB  - Experimental results of thermal emittance from lamellar gratings in intrinsic
      silicon are presented along with a theoretical discussion. For azimuthal angular
      directions in shallow gratings, enhanced thermal emission plateaus and maxima are
      observed. In the case of p-polarized emission in the Phi = 90 degrees azimuth
      (parallel to the grating vector), the plateau arises when two diffractive orders
      can be supported; it lies between the Rayleigh polar angles corresponding to the
      forbidden zone. The experimentally observed angular dependence of the s-polarized
      emission for the Phi = 90 degrees azimuth has been compared with a coupled-wave
      calculation, and a respectable agreement has been obtained. For the
      experimentally observed s-polarized emission in the Phi = 0 degrees azimuth
      (perpendicular to the grating vector), there is an onset of enhanced emission at
      the polar angles that follows a simple empirical relation unrelated to any known
      diffraction law. By contrast, the p-polarized emission in the Phi = 0 degrees
      azimuth shows relatively little structure. These data illustrate the value of
      thermal emission for surveying multivariate absorption processes involving
      microstructures.

PMID- 20820337
TI  - Inexpensive near-infrared diode-laser-based detection system for ammonia.
AB  - An inexpensive and portable ammonia monitoring system based on near-infrared GaAs
      type diode lasers is described. The minimum detectable ammonia concentration is 2
      parts in 10(6) at 100 Torr (with 1-s response time and 1-m absorption path
      length).

PMID- 20820338
TI  - External cavity semiconductor laser with a Fourier grating and an aspheric lens.
AB  - To obtain a stable single longitudinal mode oscillation of an external cavity
      laser diode, we must achieve strong coupling between the laser diode and the
      external cavity. An external cavity laser with an AlGaAs/GaAs laser diode, a
      Fourier grating, and an aspheric glass lens has been designed and fabricated. The
      Fourier grating has high diffraction efficiency independent of polarization. The
      antireflection-coated aspheric lens decreased optical coupling losses because of
      its low aberration and high transmittance. This laser oscillated stably in a
      single longitudinal mode at ~ 0.8 microm, and the oscillation wavelength was
      tunable in the region of 45 nm with a side-mode suppression ratio of less than 
      35 dB. The coupling efficiency presented by the effective amplitude reflectivity
      of the external cavity was estimated to be 0.63. A linewidth of less than 100 kHz
      was obtained.

PMID- 20820339
TI  - Graded index profile of anodic alumina films that is induced by conical pores.
AB  - The size and the shape of micropores in anodic alumina films are studied by
      electron microscope observation and mercury intrusion porosimetry. Pores have
      conical shapes with ~ 10-nm diameters and are widened at the rate of ~ 0.05
      nm/min by immersion in a sulfuric acid solution. Such conical pores give rise to
      the refractive-index distribution and anisotropy in the alumina films. By
      analyzing interference fringes, we find that a graded-index profile, as well as
      birefringence, exists in the anodic alumina films. The experimental results are
      in good agreement with theoretical predictions.

PMID- 20820340
TI  - Dielectric properties of silver halide and potassium halide crystals.
AB  - The refractive indices of mixed AgCl(x)Br(1-x) crystals, with x ranging from 0 to
      1, are measured at three wavelengths: 0.6328, 2.94, and 10.6 microm. A nonlinear
      dependence of the refractive index on composition is observed and explained on
      the basis of a simple Lorentz-Lorenz classical approximation. The theoretical
      dependence of the static dielectric constant on composition is also calculated.
      The same calculation is applied to KCl(x)Br(1-x) crystals, and, in both crystal
      systems, good agreement with experiment is obtained.

PMID- 20820341
TI  - Domain inversion in MgO-diffused LiNbO(3).
AB  - We obtain the periodic modulation of domain polarization by patterning MgO on the
      positive C-face of LiNbO(3), followed by Li outdiffusion to induce domain
      inversion. We obtain domain inversion lines (1.5 microm) by heat treating
      LiNbO(3) at 1000 degrees C for 2 h with a 1-microm inversion depth. This process
      may be suitable for fabrication of first-order gratings that are needed for high
      second-harmonic conversion efficiency by using a quasi-phase-matched technique.

PMID- 20820342
TI  - Efficient NH(3) laser operation in the 1 6- to 21 -microm region.
AB  - An optically pumped NH(3) laser is simultaneously pumped by two pulsed CO(2)
      lasers operating on the 9R(30) and 9R(24) transitions. Inversion is created in
      the NH(3) 2v(2)-to-v(2) band, and line-tunable radiation is generated in the 16-
      to 21-microm region. The maximum pulse energy observed is 100 mJ, with a photon
      conversion efficiency from 9 to 18 microm of approximately 14%.

PMID- 20820343
TI  - Measurements of the divergence evolution of a copper-vapor laser output by using
      a cylindrical imaging technique.
AB  - The temporal evolution of divergence of the output of a copper-vapor laser (CVL)
      operating with a high-magnification (M = 26.5) unstable resonator is measured by
      using a one-dimensional imaging system together with a fast gated linear diode
      array detector. The CVL output is found to consist of several temporally resolved
      components, with each successive component having lower divergence. The final
      component of the output has essentially diffraction-limited divergence. The
      divergence behavior is modeled by using an unfolded resonator-equivalent lens
      guide, with geometric constraints on the propagation of spontaneous emission
      within the lens guide, and is found to match the experimentally determined
      behavior.

PMID- 20820344
TI  - Observation of vacuum ultraviolet laser oscillation in nitric oxide.
AB  - We report recent experiments that demonstrate the line tunability of a fluorine
      laser-pumped nitric oxide laser. Laser oscillation has been observed at 589, 234,
      226, 218, 211, and 163 nm. The possibility of achieving laser oscillation on
      further UV and vacuum UV laser transitions in nitric oxide is discussed.

PMID- 20820345
TI  - Investigation of 2.1-microm lasing properties of Ho:Tm:Cr:YAG crystals under
      flash-lamp pumping at various operating conditions.
AB  - Flash-lamp-pumped normal-mode and Q-switched 2.1-microm laser operations of
      Ho:Tm:Cr:YAG crystals have been evaluated under a wide variety of experimental
      conditions in order to determine an optimum lasing condition and to characterize
      the laser outputs. Q-switched laser-output energies equal to or in some cases
      more than the normal-mode laser energies were obtained in the form of a strong
      single spike by optimizing the opening time of a lithium niobate Q switch. The
      increase of the normal-mode laser slope efficiency was observed with the increase
      of the Tm concentration from 2.5 to 4.5 at. % at operating temperatures from 120
      K to near room temperature. Laser transitions were observed only at 2.098 and
      2.091 microm under various conditions. The 2.091-microm laser transition appeared
      to be dominant at high-temperature operations with low-reflective-output couplers
      and to have an energy-level assignment from 5313 cm(-1) to 534 cm(-1) or (and)
      from 5313 cm(-1) to 536 cm(-1).

PMID- 20820346
TI  - Temperature distribution in side- and end-pumped laser crystal rods: temporal and
      spatial variations.
AB  - Knowledge of the temperature distribution of laser rods end pumped by laser
      diodes or other laser systems is relevant when thermal stress and crystal damage
      are expected. The temperature of a multipulsed or continuously pumped laser rod
      is given as a double-series expression and as a function of time. The
      mathematical model considers all surface cooling rates, the spatial and temporal
      variations of the pump beam, and the specific heat and thermal conductivity of
      the rod material. This eigenfunction expansion representation was employed to
      predict the spatial and time-dependent quasi-steady-state temperature in
      Ti:sapphire, Nd:YAG, and Cr:LiSAF laser rods of specific dimensions.

PMID- 20820347
TI  - Tunable frequency stabilized diode-laser-pumped Tm, Ho:YLiF(4) laser at room
      temperature.
AB  - A diode-laser-pumped single-frequency thulium holmium yttrium lithium fluoride
      laser that exhibits a closed-loop stability of a few megahertz and a continuous
      single-mode tuning range of 800 MHz is described. The laser output power is 25 mW
      and is tunable over ~ 8 cm(-1) at 25 degrees C.

PMID- 20820348
TI  - Performance of a Nd:YVO(4) microchip laser with continuous-wave pumping at
      wavelengths between 741 and 825 nm.
AB  - We report the performance of a Nd:YVO(4) laser, which uses cw Ti:sapphire
      pumping, for a range of pumping wavelengths, polarizations, and crystal
      temperatures.

PMID- 20820349
TI  - Conical emission by four-photon parametric generation by using femtosecond laser
      pulses.
AB  - Conical continuum Stokes and anti-Stokes emissions are observed when intense 100
      fs/620-nm ultrafast laser pulses propagate through an ethylene glycol medium. The
      angle of the anti-Stokes conical emission is modeled by class-II Raman and four
      photon parametric generations in a small-scale filament with a nonlinear index
      change.

PMID- 20820350
TI  - Mode transforming properties of tapered single-mode fiber microlenses.
AB  - The Gaussian approximation that is typically used to estimate single-mode fiber
      microlens performance is investigated. It is applied to hemispheric lenses on two
      types of tapered single-mode fiber. Theoretical and experimental results are
      compared. The first type of taper, which is fabricated by pulling a fiber while
      it is melted, has a tapered core and a tapered cladding. The second type of
      taper, which is fabricated by etching the cladding, has a tapered cladding only.
      For a tapered-core fiber, coupling to the cladding-guided modes and the finite
      radius of curvature of the wave front before the lens must be considered to
      predict the lens spot size accurately, whereas the spot size of a tapered
      cladding lens can be predicted from the lens diameter alone. Thus the spot size
      of a lens on a tapered-cladding fiber is easier to predict and control than that
      of a lens on a tapered-core fiber. It is also shown that the usual theory used to
      predict the spot size gives accepted values for tapered-cladding lenses but not
      for tapered-core lenses.

PMID- 20820351
TI  - Phase sensitivity of the output intensities of an S-shaped two-coupler fiber-ring
      resonator.
AB  - A comparison between the computed phase sensitivities of the output intensities
      of an S-shaped two-coupler fiber-ring resonator and a two-coupler single-fiber
      ring resonator, as well as a single-coupler single-fiber-ring resonator have been
      made. It is found that under certain conditions the phase sensitivities of the
      reflected and the transmitted output intensities of the S-shaped two-coupler
      fiber-ring resonator are the largest.

PMID- 20820352
TI  - Effective reflectivity of hyperbolic microlenses.
AB  - We investigate the effective reflectivity of a hyperbolic microlens. At its
      position of peak coupling, this type of lens, which couples more power into a
      single-mode optical fiber than any other reported microlens, is found to reflect
      ~ -40 dB of the incident optical power back into a typical semiconductor laser.
      This reflectivity induces a peak-to-peak shift of 3.7 GHz in the lasing frequency
      of the 1.53-microm multiquantum-well distributed Bragg reflector laser that is
      tested. The addition of a two-layer dielectric coating diminishes the frequency
      shift by over an order of magnitude, which corresponds to a lens reflectivity of
      ~ -60 dB. A comparison is made with standard hemispheric microlenses.

PMID- 20820353
TI  - Characterization of the minimum intrinsic optical time domain reflection
      signature from poly(methyl methacrylate) fiber splices.
AB  - Optical time domain reflectometry (OTDR) measurements are performed to
      characterize the minimum reflection signature from poly(methyl methacrylate)
      plastic-fiber splices. The dominant splice reflection sources that are due to
      inexact index matching and fiber core misalignment are eliminated. A clearly
      detectable intrinsic OTDR reflection signature is observed with all tested
      fibers. The measured reflectivities vary from -53 to -27 dB. The characteristics
      of this signature are mapped out versus experimental variables such as fiber
      surface roughness, fiber-surface preparation technique, indexmatching-fluid
      refractive index, and wavelength.

PMID- 20820354
TI  - Waveguide coupler for potassium- and silver-ion-exchanged waveguides in glass.
AB  - A waveguide coupler for integrating potassium- and silver-ion-exchanged glass
      waveguides in a single device is proposed and demonstrated. The measured
      insertion loss is 1.2 dB.

PMID- 20820355
TI  - Gaussian beams from variable groove depth grating couplers in planar waveguides.
AB  - Analysis, fabrication, and characterization of variable groove depth planar
      waveguide grating couplers are presented. A formula is derived to describe the
      grating groove depth variation necessary to produce an outcoupled beam of
      arbitrary profile. A variable depth grating for producing a Gaussian beam profile
      is fabricated on a waveguide by ion-beam etching through a scanning slit
      apparatus. A photoresist grating placed on the waveguide provides a mask to
      define the grating etched onto the waveguide. The near-field irradiance of the
      outcoupled beam is measured and shown to approach a Gaussian profile.

PMID- 20820356
TI  - Blocked impurity band detectors applied to tunable diode laser spectroscopy in
      the 8- to 28-microm range.
AB  - A novel tunable diode laser spectrometer operating at 8 < lambda < 28 microm is
      described. A blocked impurity band Si:As chip is employed as detector. This
      device operates in this wavelength range with high detectivity and adequate
      frequency response for the high-sensitivity techniques used. A combination of
      sweep averaging and second-harmonic detection at 22 kHz yielded signal-to-noise
      ratios of 1200 at lambda > 20 microm. The sensitivity and spectral resolution
      achieved are 1 order of magnitude better than those of Fourier instruments in
      this range, with an improvement in instrument time response of ~ 3000. Several
      molecular bands of CO(2) and N(2)O are observed for what is, to our knowledge,
      the first time with this instrument. Examples of spectral line measurements are
      presented.

PMID- 20820357
TI  - Effects of refractive turbulence on coherent laser radar.
AB  - The leading-order effects of refractive turbulence are calculated for a general
      coherent laser radar with beam-angle and beam-offset misalignment. The effects of
      refractive turbulence are important for 10-microm operation in the atmospheric
      surface layer for typical daytime conditions and paths longer than 3 km. The
      effects for near-infrared and visible wavelengths are more pronounced. The
      behavior of different parameter regimes are related to the scintillation scales
      of the transmitted beam. In certain cases, the small-scale scintillation
      structure produces a measure of beam misalignment that is more sensitive than the
      free-space case. The phase approximation of the extended Huygens-Fresnel
      principle is shown to be correct in the limit of large path-integrated refractive
      turbulence.

PMID- 20820358
TI  - Errors introduced by a quarter-wave plate in photoelastic multimode optical fiber
      sensors.
AB  - The errors that are introduced by a quarter-wave plate are theoretically
      evaluated for photoelastic multimode fiber sensors with different configurations.
      The results indicate that, for the orthogonal and parallel fiber sensors, the
      error is proportional to the change in the differential retardation of the
      quarter-wave plate, whereas the error is proportional to the square of the change
      for the pi/4 fiber sensor.

PMID- 20820359
TI  - Optical visualization of the velocity distribution in a laser-induced
      thermocapillary liquid flow.
AB  - A liquid film of black oil is heated by a cw Gaussian laser beam. This process
      gives rise to time-increasing, axisymmetric temperature distribution with a
      maximum in the laser-beam axis. Because the surface tension is decreasing
      function of temperature, a centrifugal stress gradient and concurrent liquid flow
      build up in the liquid surface. This phenomenon (known as laser-induced
      thermocapillary liquid flow) is visualized in the far field of the reflected
      laser beam, where images microscopic bubbles traveling with the liquid appear as
      bright spots. Time-resolved experimental records show that the bubbles's images
      follow rectilinear trajectories at an approximately constant speed. This result
      is explained by using the theoretical expression of velocity distribution in
      thermocapillary liquid flow.

PMID- 20820361
TI  - Velocity bias technique for particle image velocimetry measurements of high-speed
      flows.
AB  - An optical velocity bias device for use with the particle image velocimetry
      technique is implemented and successfully used to map a high-speed flow with
      velocity reversal and a large dynamic range.

PMID- 20820360
TI  - Response of two-phase droplets to intense electromagnetic radiation.
AB  - The response of two-phase droplets to intense radiant heating is studied to
      determine the incident power that is required for causing explosive boiling in
      the liquid phase. The droplets studied consist of strongly absorbing coal
      particles dispersed in a weakly absorbing water medium. Experiments are performed
      by confining droplets (radii = 37, 55, and 80 microm) electrodynamically and
      irradiating them from two sides with pulsed laser beams. Emphasis is placed on
      the transition region from accelerated droplet vaporization to droplet
      superheating and explosive boiling. The time scale observed for explosive boiling
      is more than 2 orders of magnitude longer than published values for pure liquids.
      The delayed response is the result of energy transfer limitations between the
      absorbing solid phase and the surrounding liquid.

PMID- 20820362
TI  - Opening rate of the transverse cusp diffraction catastrophe in light scattered by
      oblate spheroidal drops: errata.

PMID- 20820363
TI  - T-matrix approach for calculating local fields around clusters of rotated
      spheroids.
AB  - A T-matrix formalism is used to calculate local electric fields around clusters
      of prolate spheroids in the long-wavelength regime. The calculations are
      performed as a function of interparticle distance as well as angle of
      orientation. The observed red shifts in the resonant wavelengths of the
      characteristic peaks are shown to obey an exponential relationship as a function
      of interparticle separation and a sinusoidal relationship as a function of angle
      of rotation of the spheroid. The behavior of the cluster is discussed and the two
      effects of separation and rotation are compared.

PMID- 20820364
TI  - Remote sensing of cirrus cloud parameters using advanced very-high-resolution
      radiometer 3.7- and 1 O.9-microm channels.
AB  - We develop a retrieval scheme by using advanced very-high-resolution radiometer
      (AVHRR) 3.7- and 10.9-microm data to compute simultaneously the temperature,
      optical depth, and mean effective ice-crystal size for cirrus clouds. The
      methodology involves the numerical solution of a set of nonlinear algebraic
      equations derived from the theory of radiative transfer. The solution requires
      the correlation of emissivities of two channels in terms of the effective
      extinction ratio. The dependence of this ratio on ice-crystal size distribution
      is examined by using an adding-doubling radiative transfer program. Investigation
      of the effects of cirrus parameters on upwelling radiances reveals that the
      brightnesstemperature difference between the two channels becomes larger for
      colder cirrus and smaller ice-crystal sizes. We apply the current retrieval
      scheme to satellite data collected at 0930 UTC, 28 October 1986, over the region
      of the First International Satellite Cloud Climatology Project Regional
      Experiment CirrusIntesive Field Observation. We select the data over an area (~
      44 degrees N, 92 degrees W) near Fort McCoy, Wisconsin, for analysis. The
      retrieved cirrus heights compare reasonably well with lidar measurements taken at
      Fort McCoy 2 h after a satellite overpass at the target region. The retrieved
      mean effective crystal size is close to that derived from in situ aircraft
      measurements over Madison, Wisconsin, six hours after a satellite overpass.

PMID- 20820365
TI  - Asymptotic expansion of morphological resonance frequencies in Mie scattering.
AB  - A high-order asymptotic expansion for the size parameters x(n)((l)) of
      electromagnetic resonances of large spherical dielectric scatterers is reported.
      The expansion is calculated up to order n(-8/3), where n is the mode number and
      is valid for small orders l. Its accuracy is studied as a function of n, l, and
      the refractive index. For the l = 1 mode, the relative accuracy is better than
      10(-4) for n > 50.

PMID- 20820366
TI  - Use of polarized light to discriminate short-path photons in a multiply
      scattering medium: erratum.

PMID- 20820368
TI  - Patents.
AB  - 5,044,727; 5,116,111; 5,120,940; 5,139,331; 5,133,599; 5,139,335; 5,142,417;
      5,142,561; 5,143,435; 5,144,476; 5,144,497; 5,146,076; 5,146,080; 5,146,917;
      5,149,949; 5,149,970; 5,150,172; 5,150,966; 5,151,585; 5,151,586; 5,151,592;
      5,151,748; 5,151,820; 5,151,823; 5,151,826; 5,152,787; 5,152,788; 5,153,776;
      5,155,616; 5,155,633; 5,157,258; 5,157,458; 5,157,460; 5,157,503; 5,157,532;
      5,159,493; 5,159,496; 5,160,848; 5,161,059; 5,161,063; 5,162,949.

PMID- 20820367
TI  - Maximum concentration ratio of direct solar radiation.
AB  - I propose a refinement for a well-known formula that gives the maximum geometric
      concentration ratio of direct solar radiation.

PMID- 20820369
TI  - Temperature and strain sensitivity measurements of high-birefringent polarization
      maintaining fibers.
AB  - The strain and temperature sensitivities of three common commercial high
      birefringent polarizationmaintaining fibers (bow-tie, polarization-maintaining
      and absorption-reducing, and elliptical core fibers) have been measured by using
      a dynamic polarimetric method. The experimental setup and measuring process are
      described in detail. Where possible, the measuring data are compared with
      published data, and good agreement is obtained.

PMID- 20820370
TI  - Double-slit camera.
AB  - This Technical Note is a comment on the imaging properties of the double-slit
      camera. We show its application to the correction of geometrical distortions and
      propose some other possibilities.

PMID- 20820371
TI  - Liquid-crystal phase modulator for unpolarized light.
AB  - A simple method for phase modulating unpolarized light with a double pass through
      a nematic liquid crystal retarder is described.

PMID- 20820372
TI  - Index of refraction measurement on sapphire at low temperatures and visible
      wavelengths.
AB  - The ordinary and extraordinary refractive index of two samples of sapphire, which
      differed in the way each was grown, was measured. The measurements were made over
      a wavelength range of 477-701 nm and a temperature range of 20-295 K. A three
      term Sellmeier dispersion equation was fit to the data to permit refractive-index
      interpolation within several parts in 10(4). The data of index versus temperature
      were fit to a model and the results of dn/dT versus temperature are given along
      with certain physical constants that were extracted from the model.

PMID- 20820373
TI  - Generalization of the Ronchi, sinusoidal, and triangular rulings for Gaussian
      laser-beam-diameter measurements.
AB  - Transmittance (or reflectance) characteristics of generalized gratings are
      described for Gaussian-laserbeam-diameter measurements. The generalized gratings
      provide for accurate measurement of both small and large Gaussian beam diameters
      and are superior to the Ronchi, the triangular, and the sinusoidal rulings. Also
      the proposed generalized gratings account for all width variations of the opaque,
      transparent, and transitional regions within a selected ruling.

PMID- 20820374
TI  - Tailored edge-ray concentrators as ideal second stages for Fresnel reflectors.
AB  - For both linear and point-focus Fresnel reflectors, we present a new type of
      ideal nonimaging secondary concentrator, the tailored edge-ray concentrator, that
      can closely approach the thermodynamic limit of concentration. For large rim
      angle heliostat fields, practical-sized secondaries with shapes that should be
      relatively easy to fabricate can achieve concentrations substantially above those
      of compound parabolic concentrators. This superiority stems from designing so as
      to accommodate the particular flux from the heliostat field. The edge-ray
      principle used for generating the new secondary dictates a heliostat tracking
      strategy that is different from the conventional one but is equally easy to
      implement.

PMID- 20820375
TI  - Gaussian-to-Bessel beam transformation using a split refracting system.
AB  - A two-element refracting system is designed to transform a Gaussian laser beam
      into a diffraction-free Bessel beam. The resulting input and output surfaces are
      almost spherical, which makes for easy implementation of the system.

PMID- 20820376
TI  - Effect of axial pinhole displacement in confocal microscopes.
AB  - The effect of axial misalignment of the detector pinhole in confocal microscopes
      is investigated. We find that the use of a flat mirror to determine the axial
      position of the pinhole in a reflection microscope does not necessarily give the
      correct location. However, for a fluorescent microscope there is no uncertainty
      in determining the axial position of the pinhole by maximizing the fluorescence
      signal from a thin fluorescent film.

PMID- 20820377
TI  - Optical absorption and photoemission in semitransparent and opaque Cs(3)Sb
      photocathodes.
AB  - Optical absorption in the visible region is matched to photoelectric emission of
      cesium-antimonide photocathodes through the use of thin-film equations to explain
      the greater absorption (and hence greater sensitivity) of opaque-type
      photocathodes with the same optical constants and thickness of semitransparent
      ones. The effect is also the same for other popular photocathodes that are used
      for optical detection.

PMID- 20820378
TI  - Light scattering by red blood cells in ektacytometry: Fraunhofer versus anomalous
      diffraction.
AB  - In the present literature on ektacytometry, small angle light scattering by
      ellipsoidal red blood cells is commonly approximated by Fraunhofer diffraction.
      Calculations on a sphere with the size and relative refractive index of a red
      cell, however, show that Fraunhofer diffraction deviates significantly from exact
      Mie theory. Anomalous diffraction is found to be a much better approximation. The
      anomalous diffraction theory is used to calculate the intensity distribution of
      the light scattered by an ellipsoidally deformed red blood cell. The derived
      expression shows that the ellipticity of isointensity curves in forward scattered
      light are equal to the ellipticity of the red blood cell. The theoretical
      expression is fitted to the intensity patterns measured with an ektacytometer.
      For the small observation angles used in ektacytometry, the experimental results
      confirm the validity of the anomalous diffraction approach.

PMID- 20820379
TI  - Intensity and resolution at the diffraction focus of optical systems with
      rotationally symmetric aberration functions: erratum.

PMID- 20820380
TI  - Stepwise interferometric method of measuring the refractive index of liquid
      samples.
AB  - An iterative interferometric technique for accurately determining the refractive
      index (RI) of liquid samples is presented. The liquid is measured in an extremely
      stable stepped cell that is inserted into one arm of a Michelson-type
      interferometer. The uncertainty of the RI measurement is repeatedly improved by
      taking successive measurements of the interferometric fringe shifts on adjacent
      steps in the cell. It is shown that in practice the temperature nonuniformity in
      the liquid limits the ultimate uncertainty of the RI measurement. The RI
      resolution of the apparatus described is designed to be 4.3 x 10E-6, and the
      final RI uncertainty is 1.2 x 10E-5 (2sigma) for a liquid with a RI temperature
      coefficient of 4 x 10E-4.

PMID- 20820381
TI  - Electronic speckle photography: analysis of an algorithm giving the displacement
      with subpixel accuracy.
AB  - Replacing photographic recording by electronic processing has some obvious
      advantages. An algorithm used for electronic speckle pattern photography is
      presented, and the reliability and accuracy is analyzed by using computer
      generated speckle patterns. The algorithm is based on a two-dimensional discrete
      cross correlation between subimages from different images. Subpixel accuracy is
      obtained by a Fourier series expansion of the discrete correlation surface. The
      accuracy of the algorithm was found to vary in proportion to sigma/n(1 -
      delta)(2), where sigma is the speckle size, n is the subimage size, and delta is
      the amount of decorrelation, with negligible systematic errors. For typical
      values the uncertainty in the displacement is approximately 0.05 pixels. The
      uncertainty is found to increase with increased displacement gradients.

PMID- 20820382
TI  - Interference patterns generated by a plane-parallel plate.
AB  - A simple geometrical theory is developed to evaluate the interference pattern
      that is generated by a plane-parallel plate illuminated with a monochromatic
      point source. It is shown that a specific tilt of the plate exists with respect
      to incident illumination, at which the spatial distribution of the interference
      fringes becomes uniform. Experimental evaluation of the fringe patterns by
      superposition moire techniques supports the theoretical results.

PMID- 20820383
TI  - Efficient suppression of thermally induced nonreciprocity in fiber-optic Sagnac
      interferometers with novel double-layer winding.
AB  - A novel double-layer fiber winding that suppresses efficiently the nonreciprocity
      caused in Sagnac interferometers by temperature fields with radial temperature
      variations was proposed and analyzed.

PMID- 20820384
TI  - Automatic interference method for measuring transparent film thickness.
AB  - A new method for analytically obtaining the form of an interferogram is proposed.
      The method permits simple implementation for a computerized treatment. We can use
      it to determine easily the thickness of a thin film.

PMID- 20820385
TI  - Athermalization of a single-component lens with diffractive optics.
AB  - We describe a design method to athermalize a single-material lens element by
      using a kinoform on one surface to keep its focal length and aberrations constant
      with temperature. We diamond turned and thermally tested a plastic athermat and
      compared it to an uncompensated conventional lens.

PMID- 20820386
TI  - Nonimaging reflectors for efficient uniform illumination: errata.

PMID- 20820387
TI  - Influence of vibration on microdiameter measurements using a laser-charge-coupled
      device system.
AB  - The influence of vibration on dynamic measurements of microdiameters using a
      laser diffraction-CCD detection system is studied. The theoretical analysis
      indicates that the influence of vibration on the diffraction pattern of a
      measured object introduces significant errors into its diameter measurement, and
      the improvement can be approached by using a TEM(00) Gaussian incident beam
      instead of the usual uniform beam. The experimental results of these cases are
      also presented and in good accordance with the theoretical analysis.

PMID- 20820388
TI  - Length measurement and stabilization of optical substrates.
AB  - The initial work on the use of acoustic signals to feedback control the length of
      an optical substrate to the order of 10(-6) parts in 10(6) is described.

PMID- 20820389
TI  - High-precision detection method for the reference position in an optical encoder.
AB  - A new detection method for the reference position (zero position) of an optical
      encoder by using a diffraction grating with variable pitch is proposed. Movement
      of the diffraction grating changes the position of the grating relative to the
      radiating laser spot, altering the grating pitch that is illuminated by the laser
      and causing a change in the diffraction angle of the beam. The change is detected
      by two photodiodes. Our experiment shows that the method can provide highly
      accurate detection of the reference point in the submicrometer range.

PMID- 20820390
TI  - Velocity sensing by illumination with a laser-beam pattern.
AB  - Light reflected from an object moving through a periodical laser-beam pattern
      shows periodic intensity variation. The object's velocity can be determined from
      its frequency.

PMID- 20820391
TI  - Inexpensive range camera operating at video speed.
AB  - An optoelectronic device has been developed and built that acquires and displays
      the range data of an object surface in space in video real time. The recovery of
      depth is performed with active triangulation. A galvanometer scanner system
      sweeps a sheet of light across the object at a video field rate of 50 Hz. High
      speed signal processing is achieved through the use of a special optical sensor
      and hardware implementation of the simple electronic-processing steps. Fifty
      range maps are generated per second and converted into a European standard video
      signal where the depth is encoded in gray levels or color. The image resolution
      currently is 128 x 500 pixels with a depth accuracy of 1.5% of the depth range.
      The present setup uses a 500-mW diode laser for the generation of the light
      sheet. A 45-mm imaging lens covers a measurement volume of 93 mm x 61 mm x 63 mm
      at a medium distance of 250 mm from the camera, but this can easily be adapted to
      other dimensions.

PMID- 20820392
TI  - Photogeneration of refractive-index patterns in doped polyimide films.
AB  - A photosensitive benzophenone tetracarboxylic dianhyride-alkylated diamine
      polyimide formulation has been evaluated for application in an optical
      interconnection area. The refractive-index patterns in this material were
      optically recorded by UV-assisted photodoping of sensitizers. The polyimide films
      were selectively doped with benzoin-type photosensitizers such as
      benzildimethylketal and benzoin ethyl ether, which cause a decrease in the
      refractive index. High-dose UV irradiation that causes cross linking of the
      polyimide chains was also employed for augmenting the refractive-index difference
      to 0.017 between the doped and undoped regions. Refractive-index variations and
      lightguiding properties were investigated as a function of doping concentrations
      and other processing conditions. The author utilized this technique for the
      fabrication of embedded polyimide channel waveguides. The two photosensitizers
      have different effects on the waveguiding characteristics of the polyimide films.
      Losses for benzoin ethyl ether remained low whereas doping with
      benzildimethylketal caused significant increase in the waveguiding loss at high
      doping concentrations. Near-field imaging of the output from such waveguides
      shows good confinement of 815-nm light.

PMID- 20820393
TI  - Ellipsometry algorithm for absorbing films.
AB  - Easy sample preparation and measurement makes ellipsometry attractive for surface
      and film investigations; however, specialized numerical methods are normally
      required to relate measurements to unknown physical attributes of reflecting
      surfaces. Although solution techniques have been developed, the problem of data
      analysis is by no means solved. This paper presents an alternative method for
      computation of the thickness and optical properties of an absorbing film
      overlying a known substrate from ellipsometer data obtained at two light
      incidence angles. Tests for selected cases required no a priori knowledge of the
      film, in contrast to other methods.

PMID- 20820394
TI  - Optical properties of discontinuous copper films.
AB  - The optical properties of discontinuous copper films on quartz substrates at
      volume fractions ranging from 0.19 to 1.0 are investigated. The range of
      dielectric properties, the percolation threshold, and the range of metallic
      properties are determined. The transmittance spectra of copper films with low
      volume fractions are interpreted in terms of a modified Maxwell-Garnett theory.

PMID- 20820395
TI  - Deposition error compensation for optical multilayer coatings. II. Experimental
      results-sputtering system.
AB  - A fully automated magnetron-sputtering system for the deposition of complicated
      optical multilayer structures is described. The process control includes the real
      time determination of the deposited layer thicknesses and adjustment of the
      remaining layer thicknesses to reoptimize the final performance of the multilayer
      system. With this deposition system it should be possible to produce almost any
      all-dielectric filter that can be designed, subject only to limitations imposed
      by time, cost, and mechanical stability of the coatings. To demonstrate the
      performance of the deposition system, five complex multilayer systems were
      fabricated. The theoretical and measured spectral transmittance curves of these
      multilayer systems closely agree with one another over broad spectral regions.
      The equipment is capable of unattended operation over periods of 24 h or more.

PMID- 20820396
TI  - Multilayer interference filters for the far-infrared and submillimeter regions.
AB  - The theoretical and experimental aspects of an alternative approach to the
      construction of interference filters for wavelengths greater than 80 microm are
      described. The filters consist of a number of thin plastic sheets with films of a
      high refractive index deposited onto one or both sides of each sheet. These are
      then heat bonded to form a self-supporting optical multilayer filter.
      Experimental results are presented for a number of filters produced in this way.
      Reflectances of the order of 90% have been measured for wavelengths as high as
      ~200 microm. By successive reflections from two or more such multilayers it is
      possible to produce efficient, narrow-bandpass filters with blocking over
      extended spectral regions. The possibility of the construction of other devices,
      including even narrower bandpass filters and wideband beam splitters, is also
      discussed.

PMID- 20820397
TI  - Photographic response to x-ray irradiation. I: Estimation of the photographic
      error statistic and development of analytic density-intensity equations.
AB  - Formulations for specular optical density as a function of incident x-ray
      intensity are shown to be inadequate, theoretically and compared with available
      data. Approximations assuming low intensities, grain densities, or energies yield
      significant error in typical emulsions. Unjustifiable simplifications limit
      analysis and consequent results. The avoidance of assumptions leads to models for
      rough and smooth emulsion surfaces, which correspond to Kodak 101-01 and DEF-392
      emulsion types. The self-consistent use of spherical grains yields scaling that
      is dependent on emulsion roughness. We obtained improvement over standard
      formulations, avoiding the empirical character of earlier models and associated
      parameterization. The correlation of grain locations and occluded emulsion area
      is approximated within monolayer depths but neglected between layers. Effects of
      the incident angle from a broad source, scattering, and photoelectrons are
      considered. The models presented herein apply to the vacuum UV and x-ray energies
      from 9 eV to 20 keV and may be preferred over alternative models at lower
      energies, densities greater than unity, emulsions with high grain fractions, or
      where interpolation over energy ranges is desired. Error contributions may be
      dominated by intensity statistics or densitometry statistics. Both are inadequate
      in medium-density regimes. We have derived estimates including pseudo-binomial
      grain development statistics, using a summation over layers.

PMID- 20820398
TI  - Photographic response to x-ray irradiation. II: Correlated models.
AB  - In this paper models from the first paper are generalized so that they include
      the correlation of attenuation coefficients and coverages with emulsion depth.
      They avoid further assumptions and can provide physically meaningful parameters
      (as opposed to earlier studies); thus closer agreement with experimental
      measurements is obtained. The difficulty in estimating correlated overlap
      functions is discussed. Error estimates resulting from grain statistics are
      generalized and computed in a selfconsistent manner. Contributions to granularity
      from densitometer and grain statistics have been shown to be significant or
      dominant in most emulsion types. The formulation derives reliable error
      estimates. Correlated models are important for thick emulsions such as DEF-392,
      whereas integral formalisms may be as useful for thin emulsions. In agreement
      with the first paper, reciprocity failure appears to be negligible for UV or x
      ray energies above 9 eV.

PMID- 20820399
TI  - Photographic response to x-ray irradiation. III: Photographic linearization of
      beam-foil spectra.
AB  - In this paper models for the relation of specular density to incident (x-ray)
      intensity with uncertainties are applied to experimental data, indicating methods
      for the correction of additional effects. Linearization and error calculations
      are simplified by double linear interpolation, and the effect of this is
      quantified. Relative first-order intensities are determined directly. Secondary
      linearization or calculation for higher-order lines gives correction factors that
      yield absolute and relative higher-order intensity ratios. The effects of energy
      and angle on linearization are included. Densitometry uncertainty is estimated
      and quantified.

PMID- 20820400
TI  - Dual-waveband operation of a multilayer-coated diffraction grating in the soft x
      ray range at near-normal incidence.
AB  - A concave diffraction grating (2400 grooves/mm) coated with a Si/Mo multilayer
      has an efficiency of 2.5% at 290 A and a resolving power of 14,000 in third order
      of 156 A.

PMID- 20820401
TI  - Surface plasmon resonance microscopy: improvement of the resolution by rotation
      of the object.
AB  - A new surface plasmon resonance microscope is described that can operate at
      different resonance angles. The lateral resolution in the surface plasmon
      resonance microscope depends on the orientation of the edge of the object
      relative to the plasmon direction. By rotating the object it is possible to reach
      a resolution of the order of the wavelength. The equipment is described, and it
      is shown that a resolution of 1.5 microm is obtained for a silver-air interface
      with 675 nm. Some pictures of biological cells are presented.

PMID- 20820402
TI  - Zernike-based matrix model of deformable mirrors: optimization of aperture size.
AB  - The actuator influence functions of a typical deformable mirror are expanded in a
      Zernike polynomial decomposition. This expansion is then extended to a matrix
      formalism that describes the modal operation of the mirror. The size of the
      aperture over which the Zernikes are defined affects the accuracy of the
      expansion. The optimum size of this aperture is found by minimizing the variance
      of the wave-front error.

PMID- 20820403
TI  - Pulsed photothermal radiometry of port-wine-stain lesions.
AB  - Pulsed photothermal radiometry is used to map the heat deposition in human skin
      after a short laser pulse. It uses an IR (HgCdTe) detector for a rapid noncontact
      measurement of the skin surface temperature based on the blackbody emission in
      the 8-12-microm spectrum. The heat deposited by the laser pulse in the
      superficial epidermis causes an immediate temperature jump, and the heat
      deposited in basal epidermal melanin and deep port wine stains diffuses to the
      surface before detection. The time course of the surface temperature T(z = 0, t),
      indicates the initial spatial distribution of heat, T(z, t = 0), deposited by the
      laser.

PMID- 20820404
TI  - Role of tissue optics and pulse duration on tissue effects during high-power
      laser irradiation.
AB  - The primary zone of deposition of optical energy is called here the optical zone.
      The tissue absorption, tissue scattering, laser-beam diameter, or size of
      pigmented structures can specify the size of the optical zone. The initial
      optical zone may be altered by the formation of char during high-irradiance laser
      exposure, and a spectrum of char absorbance is presented. The relationship
      between the optical zone and the pulse duration specifies the type of laser
      tissue interaction that may occur. Short laser pulses can confine thermal energy
      and/or stress energy within the optical zone, which maximizes photothermal and
      photomechanical mechanisms of interaction.

PMID- 20820405
TI  - Acousto-optic multifrequency modulators: reduction of the phase-grating,
      intermodulation products.
AB  - The multifrequency acousto-optic modulator efficiency is limited mainly by the
      two-tone, third-order intermodulation products. We show here that a suitable
      anisotropic interaction can greatly reduce this undesirable effect. Numerical
      computations have been drawn for a paratellurite acousto-optic cell, and it is
      shown that a reduction of ~ 16 dB can be reached, limited by the acoustic
      nonlinearity intermodulation products. A specific method for experimental
      validation, based on optical heterodyning on a photodetector, is presented. The
      experimental results agree well with the theoretical ones.

PMID- 20820406
TI  - Diffractive optics: an introduction to the feature.
AB  - This feature of Applied Optics contains 16 papers on the design, fabrication,
      analysis, and applications of diffractive optics. Most of the papers originated
      from the first Optical Society of America topical meeting on diffractive optics
      that was held 13-15 April 1992 in New Orleans, Louisiana. The next diffractive
      optics topical meeting is scheduled to be held 5-9 June 1994 in Rochester, New
      York.

PMID- 20820407
TI  - Influence of temperature on diffractive lens performance.
AB  - The thermal properties of lenses play an important role in the performance of
      optical systems. We discuss the effects of uniform temperature changes and
      thermal gradients on diffractive lens performance. Comparisons are made between
      the thermal sensitivity of refractive and diffractive lenses. Useful design
      equations are presented that describe focal length, phase coefficients, and
      diffraction efficiency as functions of temperature. We present important thermal
      data for a number of lens materials. The optothermal expansion coefficient is
      used to design athermalized lenses that combine refractive and diffractive
      surfaces.

PMID- 20820408
TI  - Observation and theory of some focal properties of crossed cylindrical
      diffractive optical elements.
AB  - The observation of orthogonally crossed line foci produced by a pair of crossed
      diffractive cylindrical lenses is reported, and their origin is analyzed.

PMID- 20820409
TI  - Design and fabrication of high-efficiency beam splitters and beam deflectors for
      integrated planar micro-optic systems.
AB  - High-frequency gratings with rectangular-groove profiles are used to generate
      high-efficiency beam splitters and beam deflectors. The effects of the grating
      design parameters, i.e., period, groove depth, duty cycle, number of phase
      levels, and polarization state (TE and TM) of the incoming signal, are
      considered. The case of the binary beam splitter grating is analyzed by using
      rigorous electromagnetic grating analysis. Fabrication techniques are presented
      in which three different lithographic techniques are considered (optical contact,
      deep-UV stepper reduction, and electron-beam direct write). Experimental results
      of 97% efficiency for the beam splitter grating and up to 80% for the beam
      deflector grating are reported.

PMID- 20820410
TI  - Design and fabrication of a Gaussian fan-out optical interconnect.
AB  - A phase-retrieval algorithm is described and used to optimize the phase profile
      of a multilevel phase grating that achieves a two-dimensional Gaussian fan-out.
      Binary-optics technology is used to fabricate a surface-relief structure that
      implements this optimized phase profile. The results of the fabrication process
      are summarized, and the experimental measurements on the fan-out element are
      presented. Differences between theory and experiment arise from scalar-theory
      approximations used in the design algorithm. In order to illustrate the scalar
      theory limitations, a rigorous formulation is used to analyze the diffraction
      efficiency and the reconstruction error of a representative binary surface-relief
      phase grating as a function of the period-to-wavelength ratio. The analysis
      serves to show qualitatively the effects of the period-to-wavelength ratio on the
      performance of free-space optical interconnects designed with a scalar-theory
      formalism.

PMID- 20820411
TI  - Beam array generation and holographic interconnections in a free-space optical
      switching network.
AB  - Free-space photonic switching systems that optically interconnect large arrays of
      simple processing elements have already been demonstrated [IEEE Photon. Technol.
      Lett. 2, 438,600 (1990); Appl. Opt. 31, 5431 (1992); Electron. Lett. 27, 1869
      (1991)]. In these system experiments, diffractive optical elements served as
      critical components that provided functionality not easily assumed by
      conventional optics. In the latest optical switching network, binary phase
      gratings were used to generate arrays of uniformintensity beams to illuminate
      modulators in the processor array. In addition, space-invariant binary phase
      grating designs were integral in forming the Banyan interconnection network used
      to link arrays in the system. Here we discuss the function, design, and
      performance of these diffractive elements.

PMID- 20820412
TI  - Multilevel-grating array generators: fabrication error analysis and experiments.
AB  - The effects of mask alignment and etch-depth errors in the array uniformity error
      U and diffraction efficiency eta of multilevel-grating array illuminators are
      evaluated numerically. Also demonstrated are 16-level fan-out elements with array
      size up to 32 x 16, with U = 5%-10% and eta = 83%-92%. These are fabricated with
      electron-beam-written binary masks, optical alignment and contact copying, and
      reactive ion etching. Good-agreement-between the predictions of the-error
      analysis and the performance of the fabricated components is observed.

PMID- 20820413
TI  - Continuous-relief diffractive optical elements for two-dimensional array
      generation.
AB  - Continuous surface-relief diffractive optical elements for two-dimensional array
      generation (fan-out) are designed and fabricated. Separable and nonseparable
      solutions for the two-dimensional element design are compared. The phase-grating
      microstructures are generated by laser-beam writing lithography in a single
      exposure step and converted to nickel shims by electroplating, enabling low-cost
      replicas to be produced by using laboratory and commercial replication processes.
      Results are presented for a 9 x 9 fan-out diffractive optical element with a
      measured efficiency of 94% and an overall uniformity within +/-8%; replicas in
      epoxy have the same efficiency and a uniformity of +/-15%.

PMID- 20820414
TI  - Multiple beam generation using a stratified volume holographic grating.
AB  - The parameters of several stratified volume holographic gratings are optimized in
      order to obtain high diffraction efficiency beam spliters. Two-, three-, five-,
      seven-, and nine-beam fan-outs are theoretically studied and compared with what
      has been achieved by other means. With a simple optical setup, a fan-out element
      that generates seven beams of equal intensity is experimentally realized and a
      comparison with theory is made.

PMID- 20820415
TI  - Application of a binary diffractive optic for beam shaping in semiconductor
      processing by lasers.
AB  - Laser repair of dynamic random-access memories is commercially significant at the
      1-Mbit density and larger. The window of acceptable laser parameters required to
      repair these parts typically decreases with each successive device generation
      because of increased variations in oxide thickness. A simple single-zone binary
      optic was developed to modify the beam profile from Gaussian to flattop.
      Experiments performed on actual dynamic random-access memory parts verified a
      large increase in the laser energy process window because of the shaped beam
      profile.

PMID- 20820416
TI  - Random phase plates for beam smoothing on the Nova laser.
AB  - We discuss the design and fabrication of 80-cm-diameter random phase plates for
      target-plane beam smoothing on the Nova laser. Random phase plates have been used
      in a variety of inertial confinement fusion target experiments, such as studying
      direct-drive hydrodynamic stability and producing spatially smooth x-ray
      backlighting sources. These phase plates were produced by using a novel sol-gel
      dip-coating technique developed by us. The sol-gel phase plates have a high
      optical damage threshold at the second- and third-harmonic wavelengths of the
      Nd:glass laser and have excellent optical performance.

PMID- 20820417
TI  - Efficient storage, computation, and exposure of computer-generated holograms by
      electron-beam lithography.
AB  - An efficient storage format was developed for computer-generated holograms for
      use in electron-beam lithography. This method employs run-length encoding and
      Lempel-Ziv-Welch compression and succeeds in exposing holograms that were
      previously infeasible owing to the hologram's tremendous pattern-data file size.
      These holograms also require significant computation; thus the algorithm was
      implemented on a parallel computer, which improved performance by 2 orders of
      magnitude. The decompression algorithm was integrated into the Cambridge electron
      beam machine's front-end processor.Although this provides much-needed ability,
      some hardware enhancements will be required in the future to overcome
      inadequacies in the current front-end processor that result in a lengthy exposure
      time.

PMID- 20820418
TI  - Binary-mask generation for diffractive optical elements using microcomputers.
AB  - A new technique for generation of binary masks for the fabrication of diffractive
      optical elements is investigated. This technique, which uses commercially
      available desktop-publishing hardware and software in conjunction with a standard
      photoreduction camera, is much faster and less expensive thanhe conventional
      methods. The short turnaround time and low cost should give researchers a much
      greater degree of flexibility in the field of binary optics and enable wider
      application of diffractive-optics technology. Techniques for generating optical
      elements by using standard software packages that produce PostScript output are
      described. An evaluation of the dimensional fidelity of the mask reproduction
      from design to its realization in photoresist is presented.

PMID- 20820419
TI  - General solution to the multiple-metallic-grooves scattering problem: the fast
      polarization case.
AB  - The boundary value techniques in vector-field diffraction theories are
      generalized to describe electromagnetic scattering of plane waves by a finite
      number of parallel, rectangular grooves corrugated on a metallic (infinitely
      conducting) ground plane. Each of the grooves has its own feature size and
      location for representing a general grating structure in multilevel binary
      optics. The multiple-scattering matrix is derived for determining the scattering
      coefficients that lead to a fast convergence in the Bessel-function series
      representation of the scattered-field angular spectrum. The solution remains
      stable from the long-wavelength (the Rayleigh limit) to the short-wavelength
      region (the geometrical optics limit). It is found that any N-groove scattered
      field can be treated as the sum of N single-groove radiation fields and the cross
      groove coupling fields. A coupling index is introduced to measure the coupling
      effect. Numerical examples of two, six, and twelve grooves are examined in
      differentspectral regions. Plots of the coupling index are generated to show the
      feasibility of using pattern superposition for an approximate solution.

PMID- 20820420
TI  - Analysis of antireflection-structured surfaces with continuous one-dimensional
      surface profiles.
AB  - A novel thoretical treatment of antireflection-structured surfaces possessing
      general one-dimensional continuous profiles is presented. Closed-form solutions
      for the field reflection coefficients of these antireflection-structured surfaces
      are obtained through the use of effective medium theory and tapered transmission
      line theory. Two specific surface profiles (sinusoidal and triangular) are
      analyzed in detail. Both the sinusoidal and triangular profiles are found to
      exhibit low reflectances over a broad range of angles and wavelengths. Results
      obtained with effective medium theory and transmission-line theory are compared
      with results obtained through the application of rigorous coupled-wave analysis.

PMID- 20820421
TI  - Design and rigorous analysis of high-efficiency array generators.
AB  - One-dimensional array generators with seven to fifteen spots are designed by the
      method of virtual sources in combination with simulated-annealing optimization.
      Continuous surface-relief grating array generators and their discretized versions
      are analyzed with rigorous diffraction theory, and the results are compared with
      those obtained from Fourier-optics theory. The array-generator designs have high
      diffraction efficiency and good uniformity.

PMID- 20820422
TI  - Theory and applications of guided-mode resonance filters.
AB  - The guided-mode resonance properties of planar dielectric waveguide gratings are
      presented and explained. It is shown that these structures function as filters
      that produce complete exchange of energy between forward- and backward
      propagating diffracted waves with smooth line shapes and arbitrarily narrow
      filter linewidths. Simple expressions based on rigorous coupled-wave theory and
      on classical slab waveguide theory give a clear view and quantification of the
      inherent TE/TM polarization separation and the free spectral ranges of the
      filters. Furthermore, the resonance regimes, defining the parametric regions of
      the guided-mode resonances, can be directly visualized. It is shown that the
      linewidths of the resonances can be controlled by the grating modulation
      amplitude and by the degree of mode confinement (refractive-index difference at
      the boundaries). Examples presented of potential uses for these elements include
      a narrow-line polarized laser, a tunable polarized laser, a photorefractive
      tunable filter, and an electro-optic switch. The guided-mode resonance filter
      represents a basic new optical element with significant potential for practical
      applications.

PMID- 20820423
TI  - Patents.
AB  - 4,856,876; 5,035,481; 5,037,203; 5,037,204; 5,046,803; 5,046,817; 5,048,935
      5,048,936; 5,050,968; 5,050,990; 5,070,241; 5,071,231; 5,076,662 5,078,502;
      5,080,483; 5,080,487; 5,080,488; 5,088,824; 5,089,711; 5,090,812 5,096,279;
      5,096,297; 5,100,218; 5,100,230; 5,100,235; 5,100,236; 5,101,294 5,104,209;
      5,105,287; 5,113,402; 5,106,174.

PMID- 20820424
TI  - Nasa patter.

PMID- 20820425
TI  - Optical propagation and scattering related to the atmosphere, dense volume media,
      and rough surfaces: an introduction by the feature editors.
AB  - This issue of Applied Optics features 27 papers on topics related to optical
      propagation and scattering in the atmosphere and dense volume media and
      scattering from rough surfaces. The papers in this special issue are derived from
      presentations at the International Commission for Optics Topical Meeting
      onAtmospheric, Volume, and Surface Scattering and Propagation held in Florence,
      Italy, on 27-30 August 1991 as well as from other contributed papers on the
      subject areas covered by the meeting.

PMID- 20820426
TI  - Enhanced backscatter of a reflected beam in atmospheric turbulence.
AB  - We measure the mean and the variance of the irradiance of a diverging laser beam
      after reflection from a retroreflector and from a plane mirror in a turbulent
      atmosphere. Increases in both the mean irradiance and the normalized variance are
      observed in the direct backscatter direction because of correlation of turbulence
      on the outgoing path and the return path. The backscattered irradiance is
      enhanced by a factor of ~ 2 and the variance by somewhat less.

PMID- 20820427
TI  - Accurate numerical solutions for the frequency cross correlation of intensity
      fluctuations in a random medium.
AB  - The fourth-moment equation for the cross-frequency correlation of intensity
      fluctuations of a plane wave propagating in a random medium is solved numerically
      by using an adaptive grid method. A wide range of frequency ratios r and
      scattering strength parameters Gamma are considered, and approximate laws for the
      height and position of the peak of the covariance of intensities are obtained as
      functions of r and Gamma. Difficulties arising in the analytical solution of the
      fourth-moment equation are discussed.

PMID- 20820428
TI  - Segmented mirror alignment with far-field optimization in the presence of
      atmospheric turbulence.
AB  - The remote alignment of segmented mirror active optics with far-field
      optimization is reported. Farfield optimization eliminates the need for a wave
      front sensor or gap sensors since it does not require any near-field
      measurements, but uses simple measures of the point-spread function as figures of
      merit. The simplex function minimization algorithm is used to configure
      iteratively the segmented mirror toalignment. We present results of computer
      simulations to demonstrate the application of far-field optimization to the
      segmented mirror alignment in the presence of atmospheric turbulence. The effects
      of static as well as dynamic Kolmogorov turbulence (turbulence phase screen
      drifting across the telescope aperture) are studied. We find that the segmented
      mirror alignment is fairly insensitive to the speed of drifting turbulence and
      aligns a segmented mirror active optical system with adequate correction
      bandwidth in a few seconds.

PMID- 20820429
TI  - Model for estimating the refractive-index structure constant in clear-air
      intermittent turbulence.
AB  - We explain discrepancies in comparing estimations of the refractive-index
      structure constant C(n)(2) in clear air by means of different techniques by
      taking into account atmospheric intermittency effects. We formulate a model of
      C(n)(2) in intermittent turbulence on the basis of the Tatarskii theory, and we
      calculate the mean value of C(n)(2) through a probabilistic approach. We deduce a
      factor, which gives a measure of the statistical reduction of turbulence that is
      due to intermittency, within the model framework. A procedure for estimating the
      mean value of C(n)(2) from data of a specific radiosonde observation is
      illustrated.

PMID- 20820430
TI  - New effects in wave propagation and scattering in random media (a mini review).
AB  - An attempt is made to survey the most significant physical effects in wave
      propagation and scattering in random media that has been predicted or observed
      during the last two decades. The list of such effects includes, first, the
      phenomena of light propagation through a turbulent atmosphere: effects of
      intermittent turbulence, different phenomena in the region of strong
      fluctuations, and of the optical resolution improvement phenomena. The second
      important class under consideration consists ofenhanced backscattering and the
      related effects of double passage through the turbulent atmosphere, including
      enhancement of intensity fluctuations, partial reversal of the wave front in
      turbulent media, superfocusing, the magic-cap effect, and the diversity of other
      effects. Finally, new effects that are due to multiple scattering are discussed:
      memory effects, enhanced translucency, etc.

PMID- 20820431
TI  - Imaging through a random phase screen by enhanced backscatter: a physical
      interpretation.
AB  - It has been shown recently that enhanced backscatter processes can be exploited
      in imaging diffuserobscured objects. Through the use of an interferometric
      measurement system it is possible to determine the modulus of the Fresnel
      transform of a planar reflective object that is obscured by a thin moving
      diffuser. In a physical interpretation of that operation presented in this paper,
      we think of the object as being made up of a superposition of lens-like
      components, each with focal power appropriate to image the diffuser back onto
      itself and each with an associated attenuation and phase shift. This
      interpretation leads to the conclusion, which is verified analytically, that the
      same information about the object can be obtained without making interferometric
      measurements, i.e., without exploiting enhanced backscatter.

PMID- 20820432
TI  - Intensity correlation of a two-frequency wave at the finite-aperture detector.
AB  - The measurement of the intensity of a wave propagating in a random medium results
      in a random signal response, the statistical properties of which are functions of
      the radiation wavelength and the ratio between the characteristic scale of the
      spatial intensity pattern and the size of the receiver aperture. In this paper,
      using multiscale solutions for high-frequency random propagators, we construct
      expressions for the integral intensity correlation measures that allow us to
      obtain the spectral intensity correlationcharacteristics and to analyze their
      variations as functions of wavelength separation and detector aperture. Numerical
      results are presented for a plane wave propagating in random media that are
      characterized by a Gaussian spectrum and by a power-law spectrum of the
      refractive-index fluctuations.

PMID- 20820433
TI  - Fixed scatterer in a random medium: shadowing, enhanced backscattering, and the
      inner structure of the Bethe-Salpeter equation.
AB  - An unperturbing theory of a fixed scatterer embedded in a random medium based on
      the Bethe-Salpeter (BS) equation formalism is developed. The BS equation is
      subject to a coordinate-interchange invariance, and from that we can, to a
      considerable extent, find a basic structure of the BS equation without knowing
      details of the specific random medium involved, which leads to enhanced
      backscattering. A fixed scatterer embedded in the medium changes the basic
      equations, according to a simple principle, insuch a way that the BS equation
      formally remains unchanged. Effective scattering matrices of the fixed scatterer
      are investigated in detail, including both a shadowing effect and enhanced
      backscattering.

PMID- 20820434
TI  - Statistical properties of the Fraunhofer diffraction field produced by random
      fractals.
AB  - First-order statistical properties of the speckle field and its intensity in the
      Fraunhofer diffraction region that is produced by random Koch fractals are
      investigated by means of computer simulations in comparison with the ordinary
      fully developed speckle.

PMID- 20820435
TI  - Modification of Monte Carlo codes for use with sharply peaked phase functions.
AB  - Monte Carlo and approximate radiative transfer equation solutions predict
      different amounts of scattering for large aerosols. A new Monte Carlo scattering
      algorithm alleviates this discrepancy.

PMID- 20820437
TI  - Remote sensing of clouds by multispectral sensors.
AB  - A multispectral minimization approach that uses the wavelength dependence of the
      radiance rather than the magnitude of the radiance is advocated for the retrieval
      of cloud optical thickness, phase, and particle size by future sensors.

PMID- 20820436
TI  - Angular intensity correlations in the double passage of waves through a random
      phase screen.
AB  - <p>The problem of light scattering in folded-path or double-passage
      configurations is studied theoretically. Assuming as the random medium a deep
      phase screen that introduces Gaussian-distributed phase fluctuations, we study
      the motion of the speckle as the source is moved. Some attention is also given to
      the phenomenon of backscattering enhancement. Our analysis is based on a novel
      expression for the complex amplitude that has a simple physical interpretation.
      For simplicity, only the one-dimensional case is considered, but an extension of
      the analysis to two-dimensional screens is not difficult.</p><p>Using the
      factorization properties of the moments of a complex Gaussian process, we are
      able to derive analytical expressions for the mean intensity and the intensity
      correlation of the backscattered radiation. We find that, in most cases, the
      speckle field decorrelates rapidly as one moves the angle of incidence and shifts
      toward the direction of specular reflection with a rate of motion that is
      different from that of the angle of incidence. We also find conditions under
      which, when the angle of incidence is modified, the speckle pattern produced in
      the region of observation tracks the backscattering direction.</p>

PMID- 20820438
TI  - Use of a reference source in probability imaging.
AB  - We describe the relations between the statistics of the speckled image I(x) that
      is produced by an astronomical object at the focus of a telescope and the
      statistics of the point-source speckle pattern S(x) that is obtained under
      comparable conditions of turbulence. We show that the characteristic function
      (CF) of I(x) can be written as a central slice of a higher-order CF of S(x); as a
      consequence, probability density functions (PDF's) of I(x) and S(x) are related
      to one another by means of projections. An illustration, consisting of one
      dimensional scans obtained with the European Southern Observatory's slit-scanning
      infrared specklograph, is made for real data. It is shown how the onefold and
      twofold PDF's of a double star can be synthesized from the twofold and the
      threefold PDF's of the reference source.

PMID- 20820439
TI  - Atmospheric temperature measurements made by rotational Raman scattering.
AB  - Rotational Raman scattering of light from the second harmonic of a Nd:YAG laser
      is used to measure atmospheric temperature at altitudes of 3 to 20 km. The method
      relies on taking the ratio of light passed by two filters that differ slightly in
      their passbands, and is therefore insensitive to variations in atmospheric
      transmission. The calibration of the experiment relies on only spectroscopic
      measurements and not on normalizing to nearby radiosondes, as has been the
      previous practice with this kind of experiment. Comparisons with radiosonde
      profiles show excellent agreement to within the precision of the measurements and
      the variability of the atmosphere. The main application of the experiment lies in
      its ability to measure a time series of temperature profiles with good height
      resolution throughout a night. Examples of such series that show the passage of a
      tropopause fold above the lidar are presented.

PMID- 20820440
TI  - Scattering by a periodically corrugated interface between free space and a
      gyroelectromagnetic uniaxial medium.
AB  - Diffraction of plane waves by a corrugated grating made of a gyroelectromagnetic
      uniaxial material is set up by using the T-matrix formalism. The fully vectorial
      treatment presented here is limited in its range of applicability by the use of
      the Rayleigh hypothesis. The preferred axis of the anisotropic medium is
      considered parallel to the mean surface of the periodic interface between the
      medium and the free space. The analysis is exemplified numerically by
      calculations performed for sinusoidal gratings.

PMID- 20820441
TI  - Scattering functions near the Sun by large aerosols.
AB  - In the course of a lengthy series of observations since 1975, a large, continuous
      decrease of the brightness of the solar aureole has been found west of Boston, at
      Hanscom Air Force Base and at Lexington, Mass. This points to the virtual
      disappearance from the lower atmosphere of giant particles larger than ~ 10
      microm. in size while total suspended particulates in Boston and other U.S.
      cities have barely decreased. Results of calculations to better understand the
      relation between forward scattering and aerosol mass distribution [coarse
      fraction (CF)] are presented. In addition, a method to modify steep scattering
      functions calculated for a plane-wave source (Sun treated as a star) to those of
      the actual (and limb-darkened) Sun is presented. The calculated wavelength
      dependence of extinction, which is lower than that observed, is found to be
      little affected by the CF, but seems, like forward scattering, to be sensitive to
      mass distribution of sizes of < 0.4 and ~ 0.6 microm because of the anomal
      scattering behavior of spheres.

PMID- 20820442
TI  - Scattering of light by polyhedral ice crystals.
AB  - The single-scattering phase functions of polyhedral-shaped ice particles are
      calculated by means of geometric optics and the diffraction theory. Particle
      orientation is assumed to be random in space. Particle shapes are taken both from
      ice-crystal classifications and from in situ measurements. The effects of
      particle concavity on the scattering signature are discussed in detail. A common
      feature is the pronounced forward-scattering peak, as well as different halo
      peaks that are due to a minimum deviation at corresponding ice prisms. An unusual
      halo phenomena, which results from a minimum deviation in a double-prism
      configuration, is found and verified. The comparison of different particle types
      shows that backscattering is a sensitive indicator for the identification of
      types of ice-crystal. Aggregate particles, like bullet rosettes, basically show
      the scattering characteristics of their individual components.

PMID- 20820443
TI  - Hemispherical factors of model random-scattering composite materials.
AB  - We present an optical experimental study, in the visible and the near infrared,
      of three-dimensional random composite materials made of pellets of KBr filled
      with Ge particles with mean radius a = 5 microm. We measure hemispherical factors
      (transmittance and reflectanc6) on composite materials with various
      concentrations in a wavelength range between 0.3 and 1.8 microm. We discuss the
      results by using both the properties of single scatterers, and the radiative
      transfer theory for modeling multiple scattering in concentrated samples. Because
      of the high asymmetry factor for scattering of the Ge particles, we can assume
      that photons are scattered in only two directions, backward and forward, and we
      show that a simple two-stream theory is adequate for interpreting the main
      results as functions of both wavelength and composition, without any adjustable
      parameters.

PMID- 20820444
TI  - Radiative transfer for a three-dimensional raining cloud.
AB  - Satellite-sensor-based microwave brightness temperatures for a three-dimensional
      raining cloud over a reflecting surface are computed by using a radiative
      transfer model based on the discrete-ordinates solution procedure. The three
      dimensional model applied to a plane layer is validated by comparison with
      results from a one-dimensional model that is available in the literature. Results
      examining the effects of cloud height, rainfall rate, surface reflectance,
      rainfall footprint area, and satellite viewing position on one- and three
      dimensional brightness temperature calculations are reported. The numerical
      experiments indicate that, under certain conditions, three-dimensional effects
      are significant in the analysis of satellite-sensor-based rainfall retrieval
      algorithms. The results point to the need to consider carefully three-dimensional
      effects as well as surface reflectance effects when interpreting
      satellitemeasured radiation data.

PMID- 20820445
TI  - Multicomponent approach to light propagation in clouds and mists.
AB  - A new approach to calculating a light field with multiple scattering in media
      such as clouds, mists, and ocean water is given. It examines all characteristic
      properties of the real phase function and is applicable to a scattering medium of
      any optical thickness with an arbitrary single-scattering albedo. The phase
      function is represented as a sum of more simple functions. The radiance is given
      as a sum of appropriate components for which the equations, which can be solved
      by using a known method within domains in which they work best are obtained. The
      analytic solution of the problem of sunlight propagation in clouds and mists is
      given on this basis. It describes the complex multimodal angular radiance
      distribution. A comparison with different numerical calculations shows a fairly
      satisfactory accuracy of our analytic formulas.

PMID- 20820446
TI  - Monte Carlo calculations of the modulation transfer function of an optical system
      operating in a turbid medium.
AB  - Using a Monte Carlo method, we investigate the effect of a turbid medium on image
      transmission by means of the modulation transfer function approach. We present
      results that refer to a medium that consists of a random distribution of water
      spherical particles in air. We analyze the effect of geometric conditions (medium
      width and position) and source characteristics (Lambertian, beam emission). We
      present results for small spheres (Rayleigh scattering) and spheres (1.0-microm
      diameter) that are not small in comparison with the wavelength lambda = 0.6328
      microm. Numerical data show a large modulation transfer function dependence on
      the source emission aperture and a substantial independence of the medium width
      for a fixed value of the optical depth. In accordance with reciprocity
      principles, we test an inverse scheme of Monte Carlo calculation, the advantage
      of this scheme being a substantial reduction in calculation time.

PMID- 20820447
TI  - Anomalous interference pattern in the penumbra region of optical Gaussian beam
      diffraction on a metallic cylinder.
AB  - The diffraction pattern in the penumbra region from a metallic cylinder of radius
      p illuminated by a focused Gaussian beam waist of the half-width w approximately
      rho is experimentally studied. The observed correlation of band structure
      distortions in the diffraction pattern with calibrated deformations of the
      Gaussian beam by an opaque obstacle (which is called a label) is considered to be
      anomalous from the viewpoint of wave (interference) phenomena. The alternative
      (corpuscular) interpretation of diffracted light distribution, which is
      represented as a bundle of partially overlapping noninterfering beams propagating
      in discrete directions and preserving geometric similarity to the disturbed
      incident beams, is discussed.

PMID- 20820448
TI  - Diffraction of an elliptical Hermite-Gaussian beam on a wedge-shaped dielectric
      plate at oblique incidence.
AB  - The effect of wedge magnitude and orientation in a transparent glass plate on
      laser generation intensity at bleaching resonances of an optical laser resonator
      is experimentally investigated. Obtained experimental results are in good
      agreement with the proposed theoretical explanation, which is based on a two-beam
      interference model of multiple reflected Gaussian beams at plate interfaces.

PMID- 20820449
TI  - Iterative approach for the numerical simulation of scattering from one- and two
      dimensional rough surfaces.
AB  - We describe the use of iterative techniques for the solution of the integral
      equation that arises in an exact treatment of scalar wave scattering from
      randomly rough surfaces. The surfaces vary in either one or two dimensions, and
      the special case of a Dirichlet boundary condition is treated. It is found that
      these techniques, particularly when preconditioning is applied, are much more
      efficient than direct inversion techniques. Moreover, convergence is obtained for
      rms roughness of the order of 1, so the techniques have applicability over a wide
      parameter regime. Convergence is always to the exact solution found by direct
      inversion, exceptly for cases of extremely large-scaled rms surface heights in
      which the iterative techniques fail. In addition, by monitoring the residuals in
      the iteration process, it is immediately clear if the iterative techniques are
      failing, or performing badly in any given case. Finally, numerical results are
      compared with existing data in the enhanced backscattering regime.

PMID- 20820450
TI  - Scattering of a scalar beam from a two-dimensional randomly rough hard wall:
      Dirichlet and Neumann boundary conditions.
AB  - We calculate numerically the scattering of a scalar beam that is incident
      normally upon a large rms height, large rms slope, two-dimensional, randomly
      rough hard wall. Both Dirichlet and Neumann boundary conditions are assumed in
      these calculations. The computational approach used is based on writing the
      integral equation for the value of the normal derivative of the field, and of the
      field, respectively, on the surface, in the form of an inhomogeneous Fredholm
      equation of the second kind, and solving it by iteration. Our results display a
      well-defined peak in the retroreflection direction in the angular dependence of
      the intensity of the waves scattered incoherently, for both boundary conditions.

PMID- 20820451
TI  - Coherence in the single and multiple scattering of light from randomly rough
      surfaces.
AB  - One of the most interesting phenomena associated with the scattering of light
      from a randomly rough surface is that of enhanced backscattering. This is the
      presence of a well-defined peak in the retroreflection direction in the angular
      distribution of an incoherent component of mean scattered intensity of the light
      scattered from such a surface that is primarily due to the coherent interference
      of each multiply reflected optical path with its time-reversed partner. It is an
      example of a broader class of multiple-scattering phenomena that goes under the
      name of weak localization. Not all manifestations of weak localization in the
      interaction of light with a randomly rough surface are in backscattering. It was
      recently shown that the average diffuse intensity from randomly rough surfaces
      with even symmetry can be enhanced or reduced in the specular direction because
      of the constructive interference between correlated pairs of scatters. We present
      a recent theoretical analysis and experimental results that cover four kinds of
      enhancement: enhanced backscattering, enhanced transmission, enhanced specular,
      and enhanced refraction for one-dimensional and two-dimensional surfaces. These
      are manifestations of coherent effects that remain after ensemble averaging.

PMID- 20820452
TI  - Dynamic light scattering with single-mode and multimode receivers.
AB  - Single-mode optical fibers provide the ideal receiver optics for dynamic light
      scattering measurements. Theoretical analysis shows that with a single-mode fiber
      one can achieve a theoretical limit of 1 for the coherence factor while
      maintaining a high light-collection efficiency. In fact, the sensitivity of the
      single-mode receiver surpasses that of a classical two-pinhole setup with a
      coherence factor of 0.8 by a factor of 4 and the advantage increases rapidly when
      a still higher coherence factor is desired. In addition, a single-mode fiber
      receiver offers the possibility of working with an arbitrary large scattering
      volume and with an arbitrary working distance. All these features are also
      demonstrated experimentally by a remarkably simple apparatus that consists,
      essentially, of a commercial laser beam delivery assembly.

PMID- 20820454
TI  - The PowerPoint generation.

PMID- 20820453
TI  - [Fingolimod in the treatment of multiple sclerosis. Novelties presented at the
      annual congress of the American Academy of Neurology (Toronto, April 2010)].
AB  - Fingolimod, a sphingosine 1-phosphate receptor modulator, is currently on
      registration as an oral treatment for relapsing-remitting multiple sclerosis in
      the European Union and United States of America. New and important information on
      the drug was presented during the annual meeting of the American Academy of
      Neurology held in Toronto in April 2010, including, notably, results from the
      TRANSFORMS and FREEDOMS studies that, besides confirming the therapeutic benefit
      of the drug as a first-line therapy for multiple sclerosis, with superiority over
      interferon beta1a on clinical, inflammatory and functional outcomes, confirmed
      the safety and tolerability of the agent and described a specific benefit on the
      patients' functional abilities performing daily tasks. With additional new
      information on safety and tolerability and some new insight into the mechanism of
      action of fingolimod, new information presented during the meeting further
      supported the role of the drug in the treatment of multiple sclerosis and renewed
      hope for treating patients with a new therapeutic tool.

PMID- 20820455
TI  - A multi-faceted treatment approach for anterior reconstructions using current
      ceramics, implants, and adhesive systems.
AB  - Of all developments in dental technology, fulfilling the esthetic and functional
      demands of the patient, especially regarding anterior reconstructions, is still a
      challenge for both dentists and dental technicians. This becomes more difficult
      for patients with a previous treatment history that is not ideal. This case
      presentation demonstrates reconstruction of an anterior zirconia resin-bonded
      fixed dental prosthesis (RBFDP) for the mandible with a combined approach
      utilizing veneers for harmonized space distribution on the abutment teeth and an
      implant-supported zirconia fixed dental prosthesis in the anterior segment of the
      maxilla. Adhesive cementation of the restorations is also presented in a step-by
      step approach based on the current state of the art.

PMID- 20820456
TI  - The coronally advanced flap in combination with platelet-rich fibrin (PRF) and
      enamel matrix derivative in the treatment of gingival recession: a comparative
      study.
AB  - OBJECTIVE: The main objective of this study was to evaluate the clinical
      effectiveness of platelet-rich fibrin membrane used in combination with a
      coronally advanced flap (CAF) and to compare it with the use of an enamel matrix
      derivative (EMD) in combination with a coronally advanced flap in gingival
      recession treatment. MATERIAL AND METHODS: 20 split-mouth cases of maxillary
      anterior teeth or bicuspids presenting with Miller Class I or II gingival
      recession were treated with a CAF combined with a platelet-rich fibrin membrane
      (PRF group) or with EMD (EMD group) placed under a CAF. The following parameters
      were measured at baseline and at 12 months post treatment: gingival recession
      (GR), apicocoronal width of the keratinized tissue (WKT), and probing depth (PD).
      RESULTS: Complete rot coverage in the PRF group was 65% (13 out of 20 recessions)
      and 60% in the EMD group (12 out of 20 recessions). GR was 4.10 +/- 1.05 mm in
      the PRF group and 3.90 +/- 1.00 mm in the EMD group at baseline, and 1.05 +/-
      0.45 mm in the PRF group and 1.15 +/- 0.65 mm in the EMD group at 12 months. The
      difference observed between the tow groups at 12 months was statistically
      significant. Average root coverage was 70.5% in the EMD group and 72.1% in the
      PRF group. WKT was 1.30 +/- 0.56 mm in the EMD group and 1.45 +/- 0.86 mm in the
      PRF group at baseline, and 1.90 +/- 0.81 mm in the EMD group and 1.62 +/- 0.28 mm
      in the PRF group at 12 months. The difference observed between the two groups at
      12 months was not statistically significant. Twelve-month changes in PD were not
      significantly different between the two groups. The pain intensity was
      statistically different between the two groups. The pain intensity was
      statistically different between groups for the first 5 days, favoring the PRF
      group. CONCLUSIONS: The present study did not succeed in demonstrating any
      clinical advantage of the use of PRF compared to EMD in the coverage of gingival
      recession with the CAF procedure. The EMD group showed a higher success rate in
      increasing WKT than did the PRF group.

PMID- 20820457
TI  - Minimizing trauma during tooth removal: a systematic sectioning approach.
AB  - A prerequisite for immediate implant placement is fully intact osseous and soft
      tissue, which can only be achieved by a careful and less-traumatic tooth removal
      that minimizes damage to the soft and hard tissue structures of the extracted
      tooth socket. Traditional methods of tooth extraction using forceps and elevators
      often results in some degree of soft and hard tissue damage, which ranges from
      slight soft tissue laceration to complete loss of the buccal bony plate and
      interdental bone crest. This paper describes an extraction technique that
      utilizes a systematic tooth sectioning approach to help minimize soft and hard
      tissue loss in the extracted tooth socket.

PMID- 20820458
TI  - Effect of different finishing times on surface roughness and maintenance of
      polish in nanoparticle and microhybrid composite resins.
AB  - The objective of the study was to evaluate the effect of immediate polishing,
      after 24 h and after 1 week, on the surface roughness of two micro-hybrid resins
      (Esthet-X; Opallis) and one nanoparticle resin (Filtek Z350), as well as
      verifying maintenance of the polish after 1 year, simulated by means of thermal
      cycling. Forty-three specimens of each material were made and divided into a
      control group and three experimental groups. The control group specimens received
      no surface treatment. Group 1 received finishing with an extra-fine diamond drill
      and posterior polishing with the systems Enhance and PoGo, immediately after
      polymerization. Group 2 received the same procedures; however, these were carried
      out after 24 h of storage. Group 3 received the surface treatment after 7 days of
      storage. After that, the surface roughness was evaluated by a profilometer. After
      the initial reading, the specimens were submitted to thermal cycling for 10,000
      cycles. After thermal cycling, a new roughness reading was taken. The results
      showed a higher roughness value for the resin Esthet-X, and the resins Opallis
      and Z350 presented the same roughness values. As regards the time when polishing
      was performed, specimens polished immediately after polymerization presented
      higher roughness values in comparison with the other two periods. After thermal
      cycling, the statistical analysis showed that the Opallis resin polish had been
      maintained, whereas for the other two resins, there was a significant reduction
      in surface smoothness. The surface roughness was influenced by the material and
      also by the period of polishing; the surface roughness of all tested materials
      were at a clinically acceptable level.

PMID- 20820459
TI  - Color stability of bleached teeth over time: an in vitro study.
AB  - OBJECTIVE: The aim of this study was to evaluate the in vitro color stability of
      bleached teeth by means of a 6-day staining procedure. MATERIAL AND METHODS: 20
      caries-free randomly divided into two groups. Test group: a bleaching agent (Zoom
      2, Discus Dental) was applied to the labial surfaces following the manufacturer's
      instructions. CONTROL GROUP: no bleaching treatment. using a thermo-cycling
      device, all teeth were alternately immersed in a 0.9% saline solution at 37 
      degrees C for 1 hour, and in a coffee solution at 55  degrees C for another hour,
      in order to simulate the natural tooth-staining process. This procedure was
      repeated 12 times a day for 6 days. Teeth were polished once a day with a rubber
      cup and polishing paste. CIELAB color variables (L, a, b) were assessed by means
      of a spectrophotometer (VITA Easyshade(r)) and a custom alignment device at
      baseline, after bleaching, and once a day throughout the 6-day staining
      treatment. The bleaching result and the color stability of bleached and control
      group teeth were assessed by matched pair t test and MANOVA. RESULTS: The
      bleaching agent had a significant whitening effect. The staining treatment did
      not produce any significant color change on bleached teeth, which maintained the
      same whiteness achieved after the bleaching treatment. The staining treatment did
      not produce any significant color change on control teeth. The two groups showed
      significant differences in both whiteness and lightness changes as a result of
      the polishing treatment. CONCLUSIONS: The Zoom 2 whitening agent produced
      immediate and long-lasting bleaching results, even if the reduction of b value
      mainly occurred 24 and 48 hours after the bleaching treatment.

PMID- 20820460
TI  - Asymmetric Cu(II) catalyses for cycloaddition reactions based on pi-cation or n
      cation interactions.
AB  - The rational design of small but highly functional artificial catalysts is very
      important for practical organic synthesis. Asymmetric Lewis acid catalyses with
      non-covalent secondary interactions have been developed for enantioselective
      reactions. This tutorial review describes the concept, design and examples of
      asymmetric Cu(ii) catalyses for cycloaddition reactions based on intramolecular
      pi-cation or n-cation interactions between the copper(ii) cation and auxiliary
      Lewis basic sites of the chiral ligands.

PMID- 20820461
TI  - Tailoring cyclic polyamines for inorganic/organic phosphate binding.
AB  - In this tutorial review, we will discuss the most significant achievements in the
      structure-based design of cyclic receptors containing mainly aliphatic amine
      groups as metal-free hosts for phosphate-based guests in aqueous environment; in
      particular, inorganic phosphates and mononucleotide anions. The bulk of our
      attention will be devoted to show how this class of receptors has structurally
      evolved following the attempts by chemists to optimize all factors indicated by
      Nature as necessary to achieve the best possible binding of phosphates via non
      covalent interactions.

PMID- 20820462
TI  - Recent advances in the transmembrane transport of anions.
AB  - Anions cannot diffuse passively through biological membranes and membrane-bound
      proteins mainly govern the transmembrane movement of these charged species. The
      use of synthetic compounds that are able to facilitate the transmembrane
      transport of anions is a fascinating and burgeoning topic. The study of
      facilitated anion transport across lipid bilayers is an emerging field in
      supramolecular and bioorganic chemistry. In this critical review we describe the
      recent research progress in this area, focusing on literature published during
      the years 2007-2009. An overview of the assays that are used in the transmembrane
      transport of anions is also included (158 references).

PMID- 20820463
TI  - Boron based anion receptors as sensors.
AB  - This critical review will explore some of the recent research into the use of
      boron based anion receptors and focus on those receptors that have been designed
      to transduce the binding event into a measurable output signal. In particular the
      review will concentrate on optical chemosensors, where the signal produced is in
      the form of a colour or fluorescence change (116 references).

PMID- 20820464
TI  - A practical approach to optical cross-reactive sensor arrays.
AB  - Supramolecular analytical chemistry has emerged as a new discipline at the
      interface of supramolecular and analytical chemistry. It focuses on analytical
      applications of molecular recognition and self-assembly. One of the important
      outcomes of the supramolecular analytical chemistry is the understanding of
      molecular aspects of sensor design, synthesis and binding studies of sensors
      while using rigorous methods of analytical chemistry as a touchstone to verify
      the viability of the supramolecular aspects of the sensor design. This critical
      review provides a simplified version of the chemometric procedures involved in
      realizing a successful analytical experiment that utilizes cross-reactive optical
      sensor arrays, and summarizes the current research in this field. This review
      also shows several examples of use of described chemometric methods for
      evaluation of chemosensors and sensor arrays. Thus, this review is aimed mostly
      at the readers who want to test their newly-developed chemosensors in cross
      reactive arrays (169 references).

PMID- 20820465
TI  - Metal-salophen-based receptors for anions.
AB  - In this critical review the use of metal-salophen complexes as anion receptors is
      discussed with an emphasis on the supramolecular control of selectivity derived
      by the presence of additional interaction sites on the ligand skeleton. Some
      examples of application in sensing are also reported (112 references).

PMID- 20820466
TI  - Anion binding in covalent and self-assembled molecular capsules.
AB  - This critical review describes selected examples extracted from the extensive
      literature generated during the past 42 years on the topic of anion binding in
      molecular capsules. The goal of including anions in molecular capsules emerges
      from the idea of incorporating the traits exhibited by biological receptors into
      synthetic ones. At the outset of this research area the capsules were
      unimolecular. The scaffold of the receptor was designed to covalently link a
      series of functional groups that could converge into a cavity and to avoid its
      collapse. The initial examples involved the encapsulation of one monoatomic
      spherical anion. With time, the cavity size of the receptor was increased and
      encapsulation of polyatomic anions and co-encapsulation became a reality.
      Synthetic economy fueled the use of aggregates of self-complementary molecules
      rather than one large molecule as capsules. The main purpose of this review is to
      give a general overview of the topic which might be of interest to supramolecular
      or non supramolecular chemists alike (149 references).

PMID- 20820468
TI  - Tetracarboxylate-based Co(II), Ni(II) and Cu(II) three-dimensional coordination
      polymers: syntheses, structures and magnetic properties.
AB  - Methylenediisophthalic acid (H(4)MDIP), as semi-rigid 'V'-shaped carboxylate
      ligands, react with CoO, NiO and Cu(NO(3))(2).3H(2)O to give three novel
      coordination polymers [H(3)O](2)[Co(3)(MDIP)(2)].2DMF (1), [Ni(2)(HMDIP)(MU(2)
      OH)(H(2)O)(3)(DMF)].4H(2)O.DMF (2) and [Cu(3)(MDIP)(MU(2)
      OH)(2)(H(2)O)(4)].6.5H(2)O (3) (DMF = N,N'-dimethylformamide). All compounds have
      been characterized by thermogravimetric analysis, IR spectroscopy, elemental and
      single-crystal X-ray diffraction analyses. Complex 1 is an unusual open anionic
      framework that is defined as the metal-organic replica of fluorite. Both 2 and 3
      features a 3D open framework with one-dimensional elliptical channels and R- and
      L-helical chains, and their resulting frameworks can be rationalized as crb and
      pts topology respectively. An interesting feature of complex 3 is the presence of
      the linear Cu(3) units that is formed by carboxylate and MU(2)-hydroxyl groups
      linking three Cu(II) metal centers. Magnetic investigations indicate that
      ferromagnetic couplings are dominant in the three compounds.

PMID- 20820467
TI  - Arylethynyl receptors for neutral molecules and anions: emerging applications in
      cellular imaging.
AB  - This critical review will focus on the application of shape-persistent receptors
      for anions that derive their rigidity and optoelectronic properties from the
      inclusion of arylethynyl linkages. It will highlight a few of the design
      strategies involved in engineering selective and sensitive fluorescent probes and
      how arylacetylenes can offer a design pathway to some of the more desirable
      properties of a selective sensor. Additionally, knowledge gained in the study of
      these receptors in organic media often leads to improved receptor design and the
      production of chromogenic and fluorogenic probes capable of detecting specific
      substrates among the multitude of ions present in biological systems. In this
      ocean of potential targets exists a large number of geometrically distinct
      anions, which present their own problems to the design of receptors with
      complementary binding for each preferred coordination geometry. Our interest in
      targeting charged substrates, specifically how previous work on receptors for
      cations or neutral guests can be adapted to anions, will be addressed.
      Additionally, we will focus on the design and development of supramolecular
      arylethynyl systems, their shape-persistence and fluorogenic or chromogenic
      optoelectronic responses to complexation. We will also examine briefly how the
      "chemistry in the cuvet" translates into biological media (125 references).

PMID- 20820469
TI  - Anion receptor chemistry: highlights from 2008 and 2009.
AB  - This critical review covers advances in anion complexation in the year 2008 and
      2009. The review discusses anion receptors that employ hydrogen bond donors (both
      NH and CH), electrostatic interactions, Lewis acidic centres and combinations of
      these three types of binding interaction to complex anions. Additionally
      nanotechnological approaches to anion sensing in aqueous solution, lipid bilayer
      transporters and recent work on the use of anions to drive conformational change
      are highlighted (130 references).

PMID- 20820470
TI  - Synthesis and studies of water-soluble Prussian Blue-type nanoparticles into
      chitosan beads.
AB  - A new approach to the synthesis of highly stable aqueous colloids of coordination
      polymer nanoparticles was developed by using water-soluble chitosan beads as
      template and as stabilizing agent. The method consists in the synthesis of
      nanocomposite beads containing cyano-bridged coordination polymer nanoparticles
      via step-by-step coordination of the metal ions and the hexacyanometallate
      precursors into the chitosan pores and then water solubilization of these as
      obtained nanocomposite beads. We obtain a large range of M(2+)/[M'(CN)(6)](3
      )/chitosan (where M(2+) = Ni(2+), Cu(2+), Fe(2+), Co(2+), Mn(2+) and M' = Fe(3+)
      and Cr(3+)) nanocomposite beads and their respective aqueous colloids containing
      coordination polymer core/chitosan shell nanoparticles. The nanocomposite beads
      and the corresponding aqueous colloids were studied by Infrared (IR) and UV-Vis
      spectroscopy, nitrogen sorption (BET), Transmission Electron Microscopy (TEM),
      High Resolution Transmission Electron Microscopy (HRTEM) and magnetic analyses,
      which reveal the presence of homogeneously dispersed uniformly-sized cyano
      bridged coordination polymer nanoparticles. The detailed studies of the static
      and dynamic magnetic properties of these nanoparticles show the occurrence of a
      spin-glass like behavior presumably produced by intra-particle spin disorder due
      to the low spin exchange energy characterizing these materials.

PMID- 20820471
TI  - Variability in the response of the cyanobacterium Nodularia spumigena to nitrogen
      supplementation.
AB  - Nodularia spumigena is a filamentous cyanobacterium that is commonly found in
      brackish water bodies. The species is capable of fixing atmospheric nitrogen in
      specialized cells termed heterocysts. N. spumigena dominates the annual toxic
      summer blooms in the Baltic Sea causing environmental and economical problems. We
      have previously demonstrated that N. spumigena strain AV1 exhibits a different
      response to the presence of combined nitrogen as compared to model cyanobacteria
      such as Nostoc PCC7120 and Nostoc punctiforme by uncoupling between nitrogen
      fixation and heterocyst differentiation.In order to assess whether or not the
      behaviour of N. spumigena strain AV1 is characteristic of N. spumigena
      populations, especially in the Baltic Sea, we have investigated the effect of
      nitrate and ammonium ions on growth, nitrogen fixation activity and presence of
      heterocysts in eight different Nodularia strains. Our results show that most of
      the strains retain heterocysts in the absence of nitrogenase activity indicating
      that uncoupling between nitrogen fixation and heterocyst differentiation is most
      likely a common behaviour among N. spumigena strains, especially in the Baltic
      Sea. In addition, there are variations between strains in regard to nitrate
      uptake.

PMID- 20820472
TI  - Identity and divergence of protein domain architectures after the yeast whole
      genome duplication event.
AB  - Gene duplication is a key mechanism in evolution for generating new
      functionality, and it is known to have produced a large proportion of genes.
      Duplication mechanisms include small-scale, or "local", events such as unequal
      crossing over and retroposition, together with global events, such as chromosomal
      or whole genome duplication (WGD). In particular, different studies confirmed
      that the yeast S. cerevisiae arose from a 100-150 million-year old whole-genome
      duplication. Detection and study of duplications are usually based on sequence
      alignment, synteny and phylogenetic techniques, but protein domains are also
      useful in assessing protein homology. We develop a simple and computationally
      efficient protein domain architecture comparison method based on the domain
      assignments available from public databases. We test the accuracy and the
      reliability of this method in detecting instances of gene duplication in the
      yeast S. cerevisiae. In particular, we analyze the evolution of WGD and non-WGD
      paralogs from the domain viewpoint, in comparison with a more standard functional
      analysis of the genes. A large number of domains is shared by genes that
      underwent local and global duplications, indicating the existence of a common set
      of "duplicable" domains. On the other hand, WGD and non-WGD paralogs tend to have
      different functions. We find evidence that this comes from functional migration
      within similar domain superfamilies, but also from the existence of small sets of
      WGD and non-WGD specific domain superfamilies with largely different functions.
      This observation gives a novel perspective on the finding that WGD paralogs tend
      to be functionally different from small-scale paralogs. WGD and non-WGD
      superfamilies carry distinct functions. Finally, the Gene Ontology similarity of
      paralogs tends to decrease with duplication age, while this tendency is weaker or
      not observable by the comparison of the domain architectures of paralogs. This
      suggests that the set of domains composing a protein tends to be maintained,
      while its function, cellular process or localization diversifies. Overall, the
      gathered evidence gives a different viewpoint on the biological specificity of
      the WGD and at the same time points out the validity of domain architecture
      comparison as a tool for detecting homology.

PMID- 20820473
TI  - Dyes for biological second harmonic generation imaging.
AB  - Nonlinear optical imaging has revolutionized microscopy for the life sciences.
      Second harmonic generation (SHG), the younger sibling of two-photon excited
      fluorescence (2PF), is a technique that can produce high resolution images from
      deep inside biological tissues. Second harmonic light is generated by the
      coherent scattering of an ensemble of aligned chromophores in a focused, pulsed
      laser beam. SHG is only generated at the focal spot, reducing the background
      signal, and requires ordered chromophores, so is highly structure-specific. In
      contrast to two-photon fluorescence, the physical process that creates the signal
      does not require the formation of excited states, allowing elimination of harmful
      photochemistry. While the SHG of native proteins and biopolymers is well known,
      the use of exogenous dyes can provide SHG contrast from areas without a
      sufficiently high intrinsic quadratic hyperpolarizability, beta. Dyes for SHG
      primarily target lipid bilayers; a trait that, combined with sensitivity to
      transmembrane potential, allows monitoring of action potentials in a variety of
      excitable cells, most importantly mammalian neurons. This article summarizes the
      principles of SHG imaging and explores approaches for maximizing the SHG signal
      from a biological specimen. We survey methods of optimizing the optical set-up,
      enhancing the beta of the dye and achieving biological compatibility. In
      conclusion, we examine novel applications of SHG imaging and highlight promising
      directions for the development of the field.

PMID- 20820474
TI  - Identification of the mechanism of enhanced exciton interaction in rigidly linked
      naphthalene dimers.
AB  - Recently we characterized the low-lying electronic excitations of H-aggregated
      perylene bisimide (PBI) dyes using the time-dependent long-range-corrected
      density functional theory (TD-LRC-DFT) and the mixed intramolecular Frenkel
      exciton (FE) and the intermolecular charge-transfer exciton (CTE) model (F. Pan,
      F. Gao, W. Z. Liang and Y. Zhao, J. Phys. Chem. B, 2009, 113, 14581.). We found
      that the dimer absorption follows closely the spectra of PBI aggregates in
      solution, and demonstrates strong mixing of two kinds of excitons. Here we
      implement the theoretical approaches to study the electronic excitations of a
      family of bridged naphthalene dimers. It is found that TD-LRC-DFT reproduces all
      experimentally observed trends in the absorption profiles. By comparing the
      results obtained from the popular hybrid exchange-correlation functionals with
      these from LRC-DFT, we display how the experimentally measured dipole-allowed
      mixed exciton states of systems are formed. The major terms which contribute to
      the experimentally measured dimeric splitting are qualitatively identified. Three
      dimensional plots of transition charge density help visualize how the excitons
      couple.

PMID- 20820475
TI  - Phase stability and mechanical properties of tungsten borides from first
      principles calculations.
AB  - The phase stability and mechanical properties of tungsten borides W(2)B, WB,
      WB(2), W(2)B(5) and WB(4) were extensively studied by first-principles
      calculations within density functional theory. The thermodynamic and mechanical
      stabilities were examined. Our calculations on the enthalpy-pressure relationship
      and convex hulls have demonstrated that at zero pressure, the experimentally
      observed W(2)B-W(2)B (W(2)B-W(2)B represents W(2)B in W(2)B structure type, the
      same hereinafter) and WB-WB, and assumed WB(2)-ReB(2) phases are stable against
      decomposition into other components. The estimated hardness of WB(2)-ReB(2) is
      39.4 GPa, suggesting that it is a potentially hard compound. At 60 GPa, the most
      stable phases are WB-WB and WB(2)-WB(2). WB-WB, WB(2)-AlB(2) and WB(4) are the
      ground state phases at 100 GPa. The phase transition mechanism for WB(2) was
      discussed. The synthesis of WB(2)-AlB(2) could be conducted at high pressures.

PMID- 20820476
TI  - Mechanism study on inhibited Ru(bpy)3(2+) electrochemiluminescence between
      coreactants.
AB  - Electrochemiluminescence (ECL) derived from Ru(bpy)(3)(2+) and its derivatives
      has been proven to be useful in diverse areas of analytical chemistry. Up to date
      most of the applications are based on coreactant ECL technology. However, little
      attention has been paid to the ECL inhibition between coreactants. In this paper,
      the ECL inhibition behavior between coreactants was systematically investigated.
      The results showed that ECL inhibition happened not only within the same type of
      coreactants, but also between two different types of coreactants. Interestingly,
      for some weak coreactants, the detection methods based on ECL inhibition were
      much more sensitive than those based on ECL enhancement. Therefore, it is
      envisioned to establish sensitive inhibited ECL detection methods for these weak
      coreactants. A possible ECL inhibition mechanism related to the consumption of
      coreactant intermediates without light emission is proposed.

PMID- 20820477
TI  - Kinetic study of the fast thermal cis-to-trans isomerisation of para-, ortho- and
      polyhydroxyazobenzenes.
AB  - The thermal cis-to-trans isomerisation process has been studied for a series of
      para-, ortho- and polyhydroxy-substituted azobenzenes in different solvents. The
      kinetics of the thermal back reaction for the p-hydroxy-substituted azobenzenes
      depend strongly on the nature of the solvent used, with relaxation times ranging
      from 200-300 milliseconds in ethanol to half an hour in toluene. Otherwise, the
      process rate is mainly independent of the solvent nature for the ortho
      substituted analogues. Polyhydroxy-substituted azobenzenes show very much faster
      kinetics than the para- and ortho- monohydroxyazoderivatives. With relaxation
      times of 6-12 milliseconds in ethanol, they are optimal molecules for designing
      fast optical switching devices. All the hydroxyazoderivatives thermally isomerise
      from the metastable cis form to the thermodynamically stable trans isomer through
      a rotational mechanism.

PMID- 20820478
TI  - Rotationally resolved high-resolution spectrum of the S(1)-S(0) transition of jet
      cooled thioanisole.
AB  - The rotationally resolved high-resolution fluorescence excitation spectrum of the
      0-0 band in the S(1)<- S(0) electronic excitation of thioanisole was observed
      using the techniques of a collimated supersonic jet and a single-mode ultraviolet
      laser for the first time. High accurate rotational constants for the S(0) and the
      S(1) states have been determined by precisely calibrated transition energies of
      about 1000 assigned rotational lines. The molecular structure of thioanisole has
      been estimated by high-level MO calculations. The planarity of thioanisole in the
      S(0) and the S(1) states was also demonstrated clearly. The lifetime of the S(1)
      state was estimated to be 2.0 ns from the observed line width. This line shape
      did not change with the magnetic field of 1 Tesla, suggesting that the main
      radiationless process should be internal conversion to the S(0) state.

PMID- 20820479
TI  - Ordering aspects and intramolecular conformation of tetraphenylporphyrins on
      Ag(111).
AB  - A systematic scanning tunnelling microscopy study of the self-assembly,
      intramolecular conformation and supramolecular ordering of different
      tetraphenylporphyrins (xTPP) with or without a central metal atom (x = 2H, Fe,
      Co) on Ag(111) at room temperature is presented. The investigation covers a wide
      range, i.e. the adsorption behaviour from the low sub-monolayer up to the
      multilayer regime is described in detail and conclusively discussed in regard to
      molecule-molecule and molecule-substrate interactions. At monolayer coverage the
      molecules self-assemble in domains with a square unit cell caused by "T-type"
      intermolecular interactions, while the orientation of the domains along the
      symmetry axes is determined by adsorbate-substrate interactions. Interestingly
      for ordered monolayers domain boundaries always separate domains of different
      organizational chirality but same orientation of the square unit cell. This
      demonstrates that in the particular system chirality obviously restricts the long
      range order of the supramolecular TPP assemblies. In combination with DFT
      calculations it is also demonstrated that the previously reported intramolecular
      saddle shape deformation of TPPs upon adsorption is more pronounced for metallo
      TPP than for 2HTPP.

PMID- 20820480
TI  - An automated microfluidic platform for calcium imaging of chemosensory neurons in
      Caenorhabditis elegans.
AB  - Functional fluorescence imaging methods are widely used to study cellular
      physiology. When applied to small organisms, these methods suffer from low
      throughput due to the laborious immobilization/stimulus delivery procedure that
      is typically involved during imaging. Here, we describe the development of an
      automated microfluidic-based platform for performing automated neuronal
      functional (calcium) imaging in the roundworm Caenorhabditis elegans. The
      platform, capable of processing tens to hundreds of worms per hour, immobilizes
      individual worms, delivers a chemical odor to their nose and collects calcium
      imaging data from single neurons without any manual intervention. We used the
      developed platform to obtain a large number of calcium responses from worms of
      different ages (212 worms were imaged in total). The calcium imaging data
      revealed significant difference in the responses from young and old worms,
      indicating that neural functionality is age-dependent. We believe that such a
      technology will be an essential tool for obtaining repeatable and accurate
      functional imaging data from a large population of worms, in order to minimize
      stochastic biological noise and identify statistically significant trends.

PMID- 20820481
TI  - Ultrasound-controlled cell aggregation in a multi-well chip.
AB  - We demonstrate a microplate platform for parallelized manipulation of particles
      or cells by frequency-modulated ultrasound. The device, consisting of a silicon
      glass microchip and a single ultrasonic transducer, enables aggregation,
      positioning and high-resolution microscopy of cells distributed in an array of
      100 microwells centered on the microchip. We characterize the system in terms of
      temperature control, aggregation and positioning efficiency, and cell viability.
      We use time-lapse imaging to show that cells continuously exposed to ultrasound
      are able to divide and remain viable for at least 12 hours inside the device.
      Thus, the device can be used to induce and maintain aggregation in a parallelized
      fashion, facilitating long-term microscopy studies of, e.g., cell-cell
      interactions.

PMID- 20820482
TI  - Fluidic microstructuring of alginate hydrogels for the single cell niche.
AB  - Controlling alginate gel formation by diffusion of Ca(2+) ions through a filter
      barrier, a layer-by-layer deposition technique with resolution on the size scale
      of a single cell is presented. It offers the possibility of exposing cells under
      biocompatible conditions to microheterogeneous three-dimensional environments,
      mimicking the layered structure of extracellular matrix in tissues.

PMID- 20820483
TI  - Development of a MEMS based dynamic rheometer.
AB  - Rheological methods that interrogate nanolitre scale volumes of fluids and solids
      have advanced considerably over the past decade, yet there remains a need for
      methods that probe the frequency-dependent complex rheological moduli through
      application of homogenous strain fields. Here we describe a Micro-Electro
      Mechanical System (MEMS) based approach for the measurement of dynamic rheology
      of soft matter where oscillatory strain is produced in a sample sandwiched
      between an oscillating MEMS stage and a glass plate. The resulting stress-strain
      relationships are revealed by measurement and analysis of the stage motion. We
      present preliminary data on simple viscous fluids and on viscoelastic thin films.
      In this proof-of-principle device, we measure moduli in the range of 50 Pa to 10
      kPa over a range of 3 rad s(-1) to 3000 rad s(-1) using less than 5 nL of sample
      material. The device's measurement window is limited primarily by our current
      ability to measure the motion of the stage. This device will provide a new way to
      characterize dynamic microrheology of an array of novel materials and will prove
      useful in a number of areas including biorheology, microfluidics and polymer thin
      films.

PMID- 20820484
TI  - Matrix density mediates polarization and lumen formation of endothelial sprouts
      in VEGF gradients.
AB  - Endothelial cell (EC) sprouting morphogenesis is a critical step during
      angiogenesis, the formation of new blood vessels from existing conduits. Here,
      three-dimensional sprouting morphogenesis was examined using in vitro
      microfluidic devices that enabled the separate and simultaneous tuning of
      biomechanical and soluble biochemical stimuli. Quantitative analysis of
      endothelial sprout formation demonstrated that the ability of vascular
      endothelial growth factor (VEGF) to regulate stable sprout formation was mediated
      by the density of the surrounding collagen/fibronectin matrix. The coordinated
      migration and proliferation of multiple ECs to form stable sprouts were enhanced
      at intermediate matrix densities (1.2-1.9 mg ml(-1)), while lower densities
      resulted in uncoordinated migration (0.3-0.7 mg ml(-1)) and higher densities
      resulted in broad cell clusters that did not elongate (2.7 mg ml(-1)). Within the
      permissive range of matrix biomechanics, higher density matrices resulted in
      shorter, thicker, and slower-growing sprouts. The sprouts in higher density
      matrices also were more likely to polarize towards higher VEGF concentrations,
      included more cells per cross-sectional area, and demonstrated more stable lumen
      formation compared to sprouts in lower density matrices. These results
      quantitatively demonstrate that matrix density mediates VEGF-induced sprout
      polarization and lumen formation, potentially by regulating the balance between
      EC migration rate and proliferation rate.

PMID- 20820485
TI  - Electro-thermally induced structural failure actuator (ETISFA) for implantable
      controlled drug delivery devices based on micro-electro-mechanical-systems.
AB  - A new electro-thermally induced structural failure actuator (ETISFA) is
      introduced as an activation mechanism for on demand controlled drug delivery from
      a Micro-Electro-Mechanical-System (MEMS). The device architecture is based on a
      reservoir that is sealed by a silicon nitride membrane. The release mechanism
      consists of an electrical fuse constructed on the membrane. Activation causes
      thermal shock of the suspended membrane allowing the drugs inside of the
      reservoir to diffuse out into the region of interest. The effects of fuse width
      and thickness were explored by observing the extent to which the membrane was
      ruptured and the required energy input. Device design and optimization
      simulations of the opening mechanism are presented, as well as experimental data
      showing optimal energy consumption per fuse geometry. In vitro release
      experiments demonstrated repeatable release curves of mannitol-C(14) that
      precisely follow ideal first order release kinetics. Thermally induced structural
      failure was demonstrated as a feasible activation mechanism that holds great
      promise for controlled release in biomedical microdevices.

PMID- 20820486
TI  - High-speed RNA microextraction technology using magnetic oligo-dT beads and
      lateral magnetophoresis.
AB  - This paper presents a high-speed RNA microextractor for the direct isolation of
      RNA from peripheral blood lysate using magnetic oligo-dT beads. The extraction is
      achieved through lateral magnetophoresis, generated by a ferromagnetic wire array
      inlaid on a glass substrate. This RNA microextractor separated more than 80% of
      magnetic beads with a flow rate up to 20 ml h(-1), and the overall extraction
      procedure was completed within 1 min. The absorbance ratio of RNA to protein
      (A(260)/A(280)) was >1.7, indicating that the extraction technology yielded
      nearly pure RNA. The feasibility of this technique was evaluated further for its
      applicability to reverse transcription polymerase chain reaction (RT-PCR)
      procedures by performing cDNA synthesis and PCR. The analysis verified that the
      RNA microextractor is a practical method for easy, rapid, and high-precision RT
      PCR using minimal reagent volumes without requiring highly trained personnel. In
      addition, it can be readily incorporated into genetic analysis procedures for
      realizing automated on-chip genetic platforms in a micro format.

PMID- 20820487
TI  - A preliminary study on the activation and antigen presentation of hepatitis B
      virus core protein virus-like particle-pulsed bone marrow-derived dendritic
      cells.
AB  - Hepatitis B virus core protein virus-like particles (HBc-VLPs) act as a strong
      immunogen and are suitable for uptake by dendritic cells (DCs), in which they
      directly promote DC maturation and migration. To illustrate the utility of global
      proteomic analysis techniques in elucidating the molecular events that are
      altered in HBc-VLP-pulsed bone marrow-derived DCs (BMDCs) and to gain a better
      understanding of the molecular mechanisms of capture and processing of HBc-VLP
      pulsed BMDCs, an antigen (Ag) delivery system based on HBc-VLP-pulsed BMDCs was
      developed. Two-dimensional electrophoresis (2-DE) and tandem mass spectrometry
      (MS/MS) analyses were utilized to analyze the differential protein expression
      patterns between HBc-VLP-pulsed and untreated BMDCs. Protein spots with
      significantly altered expression levels were detected, identified and validated.
      The results showed that exogenous HBc-VLPs were phagocytosed efficiently by BMDCs
      and enhanced the efficacy of BMDC maturation and Ag presentation, VLPs also
      induced high levels of Ag-specific CD8(+) T cells that displayed high cytotoxic T
      lymphocyte (CTL) activity in vivo. Several differentially expressed proteins,
      including growth factor receptor bound protein 2 (Grb2) and annexin A2 (AnxA2),
      were detected by proteomic analysis, identified by mass spectrometry and
      validated by western blot.

PMID- 20820488
TI  - Sensitive and selective localized surface plasmon resonance light-scattering
      sensor for Ag+ with unmodified gold nanoparticles.
AB  - A novel localized surface plasmon resonance (LSPR) light-scattering sensor for
      Ag(+) was developed with unmodified gold nanoparticles (AuNPs), based upon the
      specific recognition property of Ag(+) with a cytosine-cytosine mismatched base
      pair. The addition of Ag(+) induced the oligonucleotide 5'-TAC ATA CAT ACT ATC
      TAT CTA-3' to be desorbed from the surface of the AuNPs, resulting in the
      aggregation of AuNPs, accompanied by a dramatic enhancement of the LSPR light
      scattering intensity. The enhancement of LSPR light-scattering intensity was
      proportional to the concentration of Ag(+) in the range of 0.13-1.12 MUM, with a
      limit of detection of 62.0 nM. The results were also proved by a colorimetric
      method. Furthermore, this method can provide satisfactory results for the
      determination of Ag(+) in water samples and industrial products.

PMID- 20820489
TI  - Magnetic bead-based fluorescence immunoassay for aflatoxin B1 in food using
      biofunctionalized rhodamine B-doped silica nanoparticles.
AB  - A simple and sensitive fluorescence immunoassay for the detection of aflatoxin
      B(1) (AFB(1), as a model compound) in food was developed using AFB(1)-bovine
      serum albumin conjugate (AFB(1)-BSA)-functionalized magnetic beads as
      immunosensing probes. The recognition elements were prepared by doping of
      rhodamine B (RB) fluorophore into silica nanoparticles followed by immobilization
      of monoclonal anti-AFB(1) antibodies on the silica shell. Based on a competitive
      type immunoassay format, the assay was performed both in low-binding
      polypropylene 96-well microtiter plates (MTPs) and in an automated sequential
      injection (SI) format. Similar detection limit (LOD) of 0.2 ng mL(-1)vs. 0.1 ng
      mL(-1) but narrower dynamic working linear range of 0.5-7 ng mL(-1)vs. 0.5-30 ng
      mL(-1) was obtained toward AFB(1) standards with the flow setup compared to the
      MTP format. Intra-batch assay precision was substantially improved (<=5.3%
      vs.<=8.7%) by resorting to the SI manifold. The proposed method features unbiased
      identification of negative (blank) and positive samples. No significant
      differences at the 95% confidence level were encountered in the analysis of
      naturally contaminated peanut samples between the proposed immunoassay and liquid
      chromatography for determination of AFB(1).

PMID- 20820490
TI  - Detection and quantification of adulteration in sandalwood oil through near
      infrared spectroscopy.
AB  - The confirmation of authenticity of essential oils and the detection of
      adulteration are problems of increasing importance in the perfumes,
      pharmaceutical, flavor and fragrance industries. This is especially true for
      'value added' products like sandalwood oil. A methodical study is conducted here
      to demonstrate the potential use of Near Infrared (NIR) spectroscopy along with
      multivariate calibration models like principal component regression (PCR) and
      partial least square regression (PLSR) as rapid analytical techniques for the
      qualitative and quantitative determination of adulterants in sandalwood oil.
      After suitable pre-processing of the NIR raw spectral data, the models are built
      up by cross-validation. The lowest Root Mean Square Error of Cross-Validation and
      Calibration (RMSECV and RMSEC % v/v) are used as a decision supporting system to
      fix the optimal number of factors. The coefficient of determination (R(2)) and
      the Root Mean Square Error of Prediction (RMSEP % v/v) in the prediction sets are
      used as the evaluation parameters (R(2) = 0.9999 and RMSEP = 0.01355). The
      overall result leads to the conclusion that NIR spectroscopy with chemometric
      techniques could be successfully used as a rapid, simple, instant and non
      destructive method for the detection of adulterants, even 1% of the low-grade
      oils, in the high quality form of sandalwood oil.

PMID- 20820491
TI  - In situ identification and imaging of bacterial polymer nanogranules by infrared
      nanospectroscopy.
AB  - We have employed atomic force microscope-based infrared spectroscopy (AFM-IR) to
      spatially map energy storage polymers inside individual bacteria Rhodobacter
      capsulatus. AFM-IR allows chemical mapping of sub-cellular features with a
      spatial resolution of <100 nm. We have used key absorption bands of the energy
      storage polymer polyhydroxybutyrate (PHB) known from FTIR to spatially map the
      molecular distribution of PHB inside bacteria. We have also compared FTIR
      measurements on bulk PHB with AFM-IR measurements of PHB inside bacteria. We
      observe a shift in the location of the carbonyl absorption peak between bulk PHB
      and PHB inside bacteria. We have also used finite element analysis to model AFM
      IR measurements of PHB granules, allowing for estimation of the real size of the
      granules. We have also performed transmission electron microscopy (TEM) of R.
      capsulatus to determine the size distribution of the PHB granules. Sizes measured
      by AFM-IR correspond well to TEM measurements.

PMID- 20820492
TI  - Printing conducting polymers.
AB  - Recent developments in both materials science and printing technologies have led
      to a rapid expansion in the field of printed conducting polymers. This review
      provides an overview of the most common printing methods currently in use and the
      material requirements of each. Examples of printed devices fabricated from a
      range of conducting polymers are given with an emphasis on the development of
      sensors.

PMID- 20820493
TI  - Hybrid integration of injector and detector functions for microchip gas
      chromatography.
AB  - Hybrid microchips containing high aspect ratio gas chromatograph (GC) columns
      with an integrated on-chip split injection and a flame ionization detector were
      developed. Two different column configurations, spiral and serpentine, both 1 m
      long by 50 MUm wide and 500 MUm tall, were fabricated out of electrodeposited
      nickel. The hybrid chip allowed injection plugs on the order of 1-2 ms, which
      lowered the height equivalent to theoretical plates (HETP) and allowed a
      comparison of system level band broadening between the two column configurations.
      The gas phase band broadening was estimated by measuring the flow characteristics
      and peak broadening of an unretained compound, and the results were compared with
      kinetic models. Experimental results show that both spiral and serpentine column
      layouts had similar flow and band broadening, suggesting that gas phase band
      broadening may be independent of column layout. The necessity for narrow
      injection bands for fast micro-chip chromatographic analysis was demonstrated,
      which emphasized the importance of component integration in designing powerful
      micro-analytical systems.

PMID- 20820494
TI  - Characterization and evaluation of two-dimensional microfluidic chip-HPLC coupled
      to tandem mass spectrometry for quantitative analysis of 7-aminoflunitrazepam in
      human urine.
AB  - Microfluidic chip-based high-performance-liquid-chromatography coupled to mass
      spectrometry (chip-HPLC-MS) has been widely used in proteomic research due to its
      enhanced sensitivity. We employed a chip-HPLC-MS system for determining small
      molecules such as drug metabolites in biological fluids. This chip-HPLC-MS system
      integrates a microfluidic switch, a 2-dimensional column design including an
      enrichment column (160 nL) for sample pre-concentration and an analytical column
      for chromatographic separation, as well as a nanospray emitter on a single
      polyimide chip. In this study, a relatively large sample volume (500 nL) was
      injected into the enrichment column for pre-concentration and an additional 4 MUL
      of the initial mobile phase was applied to remove un-retained components from the
      sample matrix prior to chromatographic separation. The 2-dimensional column
      design provides the advantages of online sample concentration and reducing matrix
      influence on MS detection. 7-Aminoflunitrazepam (7-aminoFM2), a major metabolite
      of flunitrazepam (FM2), was determined in urine samples using the integrated chip
      HPLC-MS system. The linear range was 0.1-10 ng mL(-1) and the method detection
      limit (signal-to-noise ratio of 3) was 0.05 ng mL(-1) for 7-aminoFM2. After
      consecutive liquid-liquid extraction (LLE) and solid-phase extraction (SPE), the
      chip-HPLC-MS exhibited high correlation between 7-aminoFM2 spiked Milli-Q water
      and 7-aminoFM2 spiked urine samples. This system also showed good precision (n =
      5) and recovery for spiked urine samples at the levels of 0.1, 1.0, and 10 ng mL(
      1). Intra-day and inter-day precision were 2.0-7.1% and 4.3-6.0%, respectively.
      Clinical urine samples were also analyzed by this chip-HPLC-MS system and
      acceptable relative differences (-1.3 to -13.0%) compared with the results using
      a GC-MC method were determined. Due to its high sensitivity and ease of
      operation, the chip-HPLC-MS system can be utilized for the determination of small
      molecules such as drug metabolites and neurotransmitters in biological fluids for
      clinical diagnosis.

PMID- 20820495
TI  - How useful is ion mobility mass spectrometry for structural biology? The
      relationship between protein crystal structures and their collision cross
      sections in the gas phase.
AB  - The technique of ion mobility mass spectrometry (IM-MS) has become of increasing
      interest for rapid analysis of the conformations adopted by biological
      macromolecules. It is currently used routinely for analysis of explosives and
      illegal substances in airport and military security. In biophysical research, it
      can be used to determine the temperature dependent rotationally averaged
      collision cross section of gas-phase ions of proteins and nucleic acids along
      with their mass to charge ratios. Nanoelectrospray ionisation allows the gentle
      transfer of intact biomolecules from solutions in which the native form(s) are
      present, into the solvent free environment of a mass spectrometer. It is believed
      by many researchers that the experimental collision cross sections of these
      molecules should have some relationship to crystal structure coordinates. In this
      review we outline the different experimental methods that can be used to measure
      ion mobility; we also describe methods used to calculate collision cross sections
      from input coordinates. Following this survey of the methodological approaches to
      IM-MS, we then summarise IM-MS data published to date for some monomeric peptides
      and small soluble proteins, along with collision cross sections calculated from
      their crystal structure coordinates. Finally we consider the relationship between
      experimental gas-phase conformations and those adopted in crystals and give an
      outlook on the application of IM-MS as a tool for structural biology.

PMID- 20820496
TI  - Fabrication and characterization of gelatin-based test materials for verification
      of trace contraband vapor detectors.
AB  - This work describes a method to produce inexpensive and field deployable test
      materials that can be used to verify the performance of trace contraband vapor
      detection systems such as ion mobility spectrometers (IMS) currently deployed
      worldwide for explosives, narcotics, and chemical warfare agent (CWA) detection.
      Requirements for such field deployable test materials include long shelf life,
      portability, and low manufacturing costs. Reported here is a method for
      fabricating these test materials using encapsulation of high vapor pressure
      compounds, such as methyl salicylate (MS), into a gelatin matrix. Gelatin serves
      as a diffusion barrier allowing for controlled and sustained release of test
      vapors. Test materials were prepared by incorporating serial dilutions of MS into
      gelatin, which provide controlled analyte vapor release over 3 to 4 orders of
      magnitude of instrument response. The test materials are simple to prepare and
      have been shown to be stable for at least one year under controlled laboratory
      conditions.

PMID- 20820497
TI  - Capillary electrophoretic development of aptamers for a glycosylated VEGF peptide
      fragment.
AB  - The emergence of functional genomics and proteomics has added to the growing need
      for improved analysis methods that can detect and distinguish between protein
      variants resulting from allelic variation, mutation, or post-translational
      modification. Aptamers, single-stranded DNA or RNA molecules that fold into three
      dimensional structures conducive to binding targets, have become an attractive
      alternative to antibodies for this type of analysis. Although aptamers have been
      developed for a wide range of target species, very few sequences have been
      identified that bind selectively to proteins with specific post-translational
      modifications. Using capillary electrophoresis-based selection, we have developed
      DNA aptamer sequences that selectively bind an N-glycosylated peptide fragment of
      vascular endothelial growth factor (VEGF). The selection method incorporates
      alternating positive- and counter-selection steps in free solution in order to
      obtain aptamers with both high affinity toward the glycosylated target and high
      selectivity versus a non-glycosylated variant. Affinity capillary electrophoresis
      and surface plasmon resonance binding assays indicate these sequences have low-uM
      dissociation constants and preferentially bind the glycosylated peptide with as
      much as 50-fold specificity. Such aptamers could serve as tools for rapid and
      simple monitoring of disease-linked functional changes in proteins, with
      potential applications in drug screening and disease diagnosis.

PMID- 20820498
TI  - Theoretical detection limits of magnetic biobarcode sensors and the phase space
      of nanobiosensing.
AB  - A scaling theory of the sub atto-molar (aM) detection limits of magnetic particle
      (MP) based biosensors (e.g., bio-barcode assays) is developed and discussed.
      Despite the dramatic differences of sensing protocols and detection limits, the
      MP-based sensors can be interpreted within the same theoretical framework as any
      other classical biosensor (e.g., nanowire sensors), except that these sensors are
      differentiated by the geometry of diffusion and the probe (rho(MP))/target
      (rho(T)) density ratio. Our model predicts two regimes for biomolecule detection:
      For classical biosensors with rho(MP) <= rho(T), the response time t(s)
      proportional to 1/rho(T); while for MP-based biosensors with rho(MP) > rho(T),
      t(s) proportional to 1/rho(MP). The theory (i) explains the performance
      improvement of MP-sensors by rho(MP)/rho(T) (order of 10(3)-10(6)), broadly
      validating the sub-aM detection limits reported in literature, (ii) offers
      intuitive interpretation for the counter-intuitive rho(T)-independence of
      detection time in MP-sensors, (iii) shows that statistical fluctuations should
      reduce with rho(T) for MP sensors, and (iv) offers obvious routes to sensitivity
      improvement of classical sensors.

PMID- 20820499
TI  - Alignment of gold nanoparticles using insulin fibrils as a sacrificial
      biotemplate.
AB  - Insulin fibrils were used as a biotemplate for creating gold nanoparticle chains
      on glass substrates, and then subsequently removed by exposing the samples to a
      low-pressure plasma, leaving the gold nanoparticles on the glass surface in their
      template positions.

PMID- 20820500
TI  - Synthesis of cRGD-peptide conjugated near-infrared CdTe/ZnSe core-shell quantum
      dots for in vivo cancer targeting and imaging.
AB  - Cyclic RGD-peptide functionalized phospholipids micelle-encapsulated near
      infrared CdTe/ZnSe quantum dots were synthesized as multifunctional probes for
      targeting and imaging tumors in live animals.

PMID- 20820501
TI  - Development of new functional nanostructures consisting of both DNA duplex and
      quadruplex.
AB  - The sequence specificity of a duplex and the cation dependent self-assembly of a
      G-quadruplex were combined to design rationally DNA G-quadruplex arrays connected
      by duplexes.

PMID- 20820502
TI  - Mystery of the transformation from amorphous calcium phosphate to hydroxyapatite.
AB  - The process from the amorphous calcium phosphate phase to the hydroxyapatite
      (HAP) crystalline phase has been captured in a simulated physiological fluid by
      combining in situ extinction detection and ex situ electronic microscopy. The
      results reveal the secret of the phase transformation and orientation controls
      during the initial stage of mineral formation.

PMID- 20820503
TI  - Anionic N,O-ligated Pd(II) complexes: highly active catalysts for alcohol
      oxidation.
AB  - There is a need to develop effective catalytic methods for alcohol oxidation.
      Pd(II) complexes have shown great promise as catalysts, however a comparatively
      small number of ligands have been reported so far. Herein we report the use of
      commercially available anionic N,O-ligands to produce highly active catalysts.

PMID- 20820504
TI  - Reactions of a beta-diketiminate zinc hydride complex with heterocumulenes.
AB  - The beta-diketiminate zinc hydride MesnacnacZnH (1) reacts with CO(2), C(Ni
      Pr)(2) and t-BuNCO at ambient temperature with insertion into the Zn-H bond and
      subsequent formation of the corresponding formato (2), formamido (3) and
      formamidinato (4) complexes.

PMID- 20820505
TI  - Giant magnetoresistance in oxypnictides (La,Nd)OMnAs.
AB  - A sizeable negative magnetoresistance (MR) has been observed for oxypnictides
      LnOMnAs (Ln = La,Nd). MR up to -24% is observed at 200 K for LaOMnAs which is
      unprecedented for divalent Mn(2+). Both materials are weak ferromagnets with
      transition temperatures above room temperature.

PMID- 20820506
TI  - Rice grain-shaped TiO2 mesostructures by electrospinning for dye-sensitized solar
      cells.
AB  - Nanofibers, produced by electrospinning a solution containing titanium tetra(IV)
      isopropoxide, polyvinyl acetate and acetic acid in N,N-dimethyl acetamide, upon
      sintering at 500  degrees C produce rice grain-shaped TiO(2) mesostructures. Each
      rice grain-shaped TiO(2) has a mixed crystal structure and high porosity and the
      mesostructures are found to have applications in dye-sensitized solar cells.

PMID- 20820507
TI  - Molecular AND-logic for dually controlled activation of a DNA-binding spiropyran.
AB  - A spiropyran photoswitch is activated using UV light and protons from a form that
      shows no interaction with DNA to a form that binds to DNA by intercalation. This
      scheme is interpreted as a biologically relevant logic AND gate with potential
      applications as a dually controlled anticancer drug.

PMID- 20820508
TI  - A "switching on" fluorescent chemodosimeter of selectivity to Zn2+ and its
      application to MCF-7 cells.
AB  - A highly sensitive and selective 1,8-naphthyridine-based fluorescent
      chemodosimeter for Zn(2+) has been designed, synthesized, and applied to the
      detection of intracellular Zn(2+).

PMID- 20820510
TI  - Direct-write assembly of microperiodic planar and spanning ITO microelectrodes.
AB  - Printed Sn-doped In(2)O(3) (ITO) microelectrodes are fabricated by direct-write
      assembly of sol-gel inks with varying concentration. This maskless, non
      lithographic approach provides a facile route to patterning transparent
      conductive features in planar arrays and spanning architectures.

PMID- 20820509
TI  - Self-assembled Ni/TiO2 nanocomposite anodes synthesized via electroless plating
      and atomic layer deposition on biological scaffolds.
AB  - Ni(core)/TiO(2)(shell) nanocomposite anodes were fabricated on three-dimensional,
      self-assembled nanotemplates of Tobacco mosaic virus using atomic layer
      deposition, exhibiting high capacities and rate capability and extremely low
      average capacity fading (~0.024% per cycle) for ~1000 cycles.

PMID- 20820511
TI  - Golf ball-shaped PLGA microparticles with internal pores fabricated by simple O/W
      emulsion.
AB  - Simple oil-in-water emulsion led to structural complexity at both the surface and
      interior of the PLGA microsphere. A golf ball-like dimpled surface comes from the
      heteroaggregation of volatile nonsolvent colloid originating from the inside of
      the organic droplet as supported by in situ optical microscopy. The internal
      porous structure and encapsulation of hydrophobic agent inside the microparticle
      implies its potential application as a drug carrier.

PMID- 20820512
TI  - Selective synthesis of trienes and dienes via nickel-catalyzed intermolecular
      cotrimerization of acrylates and alkynes.
AB  - Tailoring nickel-catalyzed linear cotrimerization of acrylates and alkynes
      effectively proceeds to produce trienes and dienes highly selectively.

PMID- 20820513
TI  - Hydrogen peroxide as sustainable fuel: electrocatalysts for production with a
      solar cell and decomposition with a fuel cell.
AB  - Hydrogen peroxide was electrochemically produced by reducing oxygen in an aqueous
      solution with [Co(TCPP)] as a catalyst and photovoltaic solar cell operating at
      0.5 V. Hydrogen peroxide thus produced is utilized as a fuel for a one
      compartment fuel cell with Ag-Pb alloy nanoparticles as the cathode.

PMID- 20820514
TI  - Dioxygen activation by mixed-valent dirhodium complexes of redox non-innocent
      azoaromatic ligands.
AB  - The isolation, structural chracterisation and electronic structure of a formally
      mixed-valent Rh(-I)-Rh(III) complex is described, along with its reaction with
      dioxygen leading to double arene hydroxylation of the coordinated ligands.

PMID- 20820515
TI  - Enhanced G4-DNA binding of 5,10,15,20 (N-propyl-4-pyridyl) porphyrin (TPrPyP4): a
      comparative study with TMPyP4.
AB  - The cationic porphyrin TPrPyP4, with four propyl substituents in the pyridinium
      rings, is evaluated in vitro by spectroscopic and polymerase-stop assays as a G4
      DNA ligand and in cultured cells as a modulator of gene transcription. A
      comparison with the widely used TMPyP4 is presented.

PMID- 20820516
TI  - Chiral cobalt-catalyzed enantioselective aerobic oxidation of alpha-hydroxy
      esters.
AB  - A chiral cobalt-catalyzed enantioselective aerobic oxidative kinetic resolution
      of (+/-)-alpha-hydroxy esters, using molecular oxygen as a sole oxidant, is
      reported and a maximum of selectivity factor (s) 31.9 was achieved with >99%
      enantiomeric excess for unreacted alpha-hydroxy esters.

PMID- 20820517
TI  - One-pot asymmetric cyclocarbohydroxylation sequence for the enantioselective
      synthesis of functionalised cyclopentanes.
AB  - A new method has been developed for the enantioselective synthesis of highly
      functionalised cyclopentanes bearing up to three stereogenic centres with very
      high stereoselectivity. This one-pot process combines an enantioselective
      organocatalytic Michael addition with a highly diastereoselective [3+2]
      cycloaddition-fragmentation step.

PMID- 20820518
TI  - Desymmetrizations of meso-tert-norbornenols by rhodium(I)-catalyzed
      enantioselective retro-allylations.
AB  - Rhodium-catalyzed desymmetrizations of meso-tert-norbornenols by retro
      allylations generate allyl-rhodium species that allow for a rich and diverse
      downstream reactivity.

PMID- 20820519
TI  - NiWO4 nanoparticles: a promising catalyst for hydrodesulfurization.
AB  - NiWO(4) nanoparticles have been facilely synthesized by a hydrothermal approach,
      and used as a catalyst for the hydrodesulfurization of thiophene and its
      derivative 4,6-dimethyldibenzothiophene, showing a significantly higher activity
      than commercial NiW/Al(2)O(3).

PMID- 20820520
TI  - Hydrogen generation by electrolysis of liquid ammonia.
AB  - Hydrogen gas is generated by the electrolysis of liquid ammonia which has high
      hydrogen capacity of 17.8 mass%. The metal amides are used as supporting
      electrolytes to dissolve the amide ion in liquid ammonia. The results presented
      here indicate that liquid ammonia is promising as an energy medium for hydrogen
      storage and generation.

PMID- 20820521
TI  - Simultaneous templating of polymer nanocapsules and entrapped silver
      nanoparticles.
AB  - Nanorattles made of hollow polymer nanocapsules with entrapped silver
      nanoparticles were synthesized in one step by using lipid vesicles as templates.
      Free radical photoinitiator facilitated both polymerization within the bilayer
      and formation of metal nanoparticles in the aqueous core.

PMID- 20820522
TI  - One-pot synthesis of conducting polymer-coated latex particles: ammonium
      persulfate as free radical initiator and chemical oxidant.
AB  - Conducting polymer-coated polystyrene latex particles were synthesized in one pot
      using ammonium persulfate as an initiator for free radical polymerization of
      styrene and a chemical oxidant for chemical oxidative polymerization. Pressed
      pellets of the core-shell particles showed an efficient electrical conduction.

PMID- 20820523
TI  - Highly sensitive protein detection based on aptamer probe and isothermal nicking
      enzyme assisted fluorescence signal amplification.
AB  - An isothermal and sensitive fluorescence assay for protein detection using
      aptamer-protein-aptamer conjugates based on nicking enzyme amplification has been
      developed, which was combined with magnetic microparticles separation, making
      this assay suitable for protein detection in biological samples.

PMID- 20820524
TI  - Facile synthesis of highly luminescent UV-blue emitting ZnSe/ZnS core/shell
      quantum dots by a two-step method.
AB  - New water-soluble and highly luminescent ZnSe/ZnS core/shell quantum dots with
      tunable emission ranging between 390 and 460 nm were synthesized via a two-step
      method.

PMID- 20820525
TI  - Alzheimer's disease amyloid beta converting left-handed Z-DNA back to right
      handed B-form.
AB  - Herein we report that Abeta aggregates, not Abeta monomer, can convert Z-DNA back
      to B-form, and curcumin, a well-known Abeta aggregation inhibitor, can stop DNA Z
      B transition studied by means of biophysical and biochemical methods.

PMID- 20820526
TI  - Advances in selective conversions by heterogeneous photocatalysis.
AB  - Selective photocatalytic conversions are offering an alternative green route for
      replacing environmentally hazardous processes with safe and energy efficient
      routes. This paper reports the most recent advances in the application of
      heterogeneous photocatalysis to synthesize valuable compounds by selective
      oxidation and reduction.

PMID- 20820527
TI  - Enzymatic single-step preparation of multifunctional proteins.
AB  - A small glutamine donor substrate was designed for single-step and site-specific
      protein multifunctionalization catalyzed by microbial transglutaminase.

PMID- 20820528
TI  - Reversible morphological switching of nanostructures in solution.
AB  - The design and synthesis of a tuneable and reversible morphology switching
      copolymer system is reported. The kinetics of the transition under a range of
      conditions has been explored, as has the stabilization of the resultant
      structures.

PMID- 20820529
TI  - Synthesis and characterization of an infinite sheet of metal-alkyl bonds:
      unfolding the elusive structure of an unsolvated alkali-metal
      trisalkylmagnesiate.
AB  - The study of co-complexation reactions between NaCH(2)SiMe(3) and
      Mg(CH(2)SiMe(3))(2) has allowed the isolation and structural elucidation of the
      first solvent-free alkali-metal alkylmagnesiate
      [{NaMg(CH(2)SiMe(3))(3)}(infinity)] (1) as well as the related solvent-free
      sodium alkyl [{(NaCH(2)SiMe(3))(4)}(infinity)] (3).

PMID- 20820530
TI  - A solid-state trimerisation of a diene diacid affords a bicyclobutyl: reactant
      structure from X-ray powder data and product separation and structure
      determination via co-crystallisation.
AB  - A bicyclobutyl that bears six carboxylic acid groups results from a trimerisation
      of a diene diacid in the solid state. Powder X-ray diffraction and a co
      crystallisation are used to solve the structure of the diene and elucidate the
      stereochemistry of the bicyclobutyl, respectively.

PMID- 20820531
TI  - Benziodoxole-based hypervalent iodine reagents for atom-transfer reactions.
AB  - In the last decades, hypervalent iodine reagents have raised from chemical
      curiosities to mainstream reagents in organic synthesis. The use of benziodoxole
      derived reagents has been especially successful in oxidation methods, whereas non
      cyclic iodinanes have been used both for oxidation and atom-transfer reactions.
      On the other hand, the exceptional properties of benziodoxole reagents for atom
      transfer reactions have only started to attract the attention of the synthetic
      community more recently. In this review, progress in the use of these compounds
      for C-X and C-C bond formations will be presented. In particular, recent
      breakthroughs in trifluoromethylation and alkynylation reactions have been
      realized since 2006 based on benziodoxole-derived reagents and these results are
      the main focus of this article.

PMID- 20820532
TI  - Aryne cycloaddition: highly efficient chemical modification of graphene.
AB  - We have developed a simple and efficient approach for the synthesis of chemically
      converted graphene sheets via aryne cycloaddition under mild reaction conditions.
      The resulting highly functionalized and thermally stable aryne-modified graphene
      sheets can be well dispersed in various solvents.

PMID- 20820533
TI  - Guest-induced capsule formation based on concerted interactions in water at
      neutral pH.
AB  - The interaction of a tetracationic calixarene (TAC4) with dianionic guest (BS) in
      water was studied with NMR, nano-ITC and ESI-MS experiments; the convergent
      evidence provided by these different techniques shows that the addition of a
      suitable guest molecule triggers the formation of a homodimeric capsule in
      aqueous neutral solution.

PMID- 20820534
TI  - A facile route to end-functionalised polymers synthesised by SET-LRP via a one
      pot reduction/thiol-ene Michael-type addition.
AB  - We report the facile synthesis of well defined, disulfide containing polymers via
      SET-LRP. A one-pot reduction/conjugation reaction enables post polymerisation
      modification with functional (meth)acrylates and acrylamides.

PMID- 20820535
TI  - Direct observation and pH control of reversed supramolecular chirality in insulin
      fibrils by vibrational circular dichroism.
AB  - The controlled reversal of supramolecular helical chirality in protein fibrils is
      reported for the first time. Normal or reversed insulin fibrils were grown by
      precise adjustment of pH. AFM images show two polymorphs corresponding to
      opposite senses of helical twist of the supramolecular structure with the same
      cross-beta-sheet core.

PMID- 20820536
TI  - Hyperbranched alternating block copolymers using thiol-yne chemistry: materials
      with tuneable properties.
AB  - Alternating-block hyperbranched polymers were synthesized using the highly
      versatile thiol-yne reaction. Dimethyl acrylamide-styrene and tert-butyl acrylate
      styrene polymers were prepared, with subsequent hydrolysis of the tert-butyl
      ester to acrylic acid. The dimethyl acrylamide-styrene hyperbranched polymers
      self-assembled into large aggregates, as did the acrylic acid-styrene system at
      low pH. However, high pH triggers the formation of very well defined small
      particles in the latter system.

PMID- 20820537
TI  - Competing ring cleavage of transient O-protonated oxaphosphirane complexes: 1,3
      oxaphospholane and eta2-Wittig ylide complex formation.
AB  - O-Protonation and ring cleavage of oxaphosphirane complexes 1a,b enabled the
      synthesis of novel compounds such as the bicyclic 1,3-oxaphospholane complex 5
      and the eta(2)-Wittig ylide complex 7, which demonstrate the emerging chemistry
      of this new reactive intermediate. Whereas P-O bond cleavage occurred, in the
      first case, thus revealing the superior ability of the P-bonded Cp* group to
      stabilize cationic charge, in the second case competing C-O and P-O bond
      cleavages occurred, thus leading to a mixture of complexes 3, 4 and 7.

PMID- 20820538
TI  - On the relationship between structure and reaction rate in olefin ring-closing
      metathesis.
AB  - In the RCM reactions of a series of simple alpha,omega-dienes, the relative order
      of reactivity has been unambiguously determined showing that cyclohexene forms
      faster than cyclopentene or cycloheptene. 1,5-Hexadiene inhibits the RCM of 1,7
      octadiene; 1,5-hexadiene cannot progress to the RCM product (cyclobutene) but
      forms an unexpectedly stable cyclic eta(2)-complex.

PMID- 20820539
TI  - Mixed N-heterocyclic carbene/phosphite ruthenium complexes: towards a new
      generation of olefin metathesis catalysts.
AB  - The synthesis, characterisation and catalytic behaviour of ruthenium indenylidene
      complexes bearing an N-heterocyclic carbene and triisopropylphosphite are
      described.

PMID- 20820540
TI  - Diazirine-containing RNA photocrosslinking probes for the study of siRNA-protein
      interactions.
AB  - We here report the synthesis and characterization of small interfering RNAs with
      aryl trifluoromethyl diazirine moieties in the 3'-overhang regions, which allow
      sensitive detection of interacting proteins during assembly of the effector
      ribonucleoprotein complex by irradiation with minimally destructive long
      wavelength ultraviolet light.

PMID- 20820541
TI  - Minimal complementary hydrogen-bonded double helices.
AB  - Molecular strands incorporating three hydrogen bond donor (D) or acceptor (A)
      heterocycles form highly stable double helical complexes through a complementary
      AAA-DDD array structure.

PMID- 20820542
TI  - Contrasting reactivity of anionic boron- and gallium-containing NHC analogues: E
      C vs. E-M bond formation (E = B, Ga).
AB  - The anionic Group 13 NHC analogues [(CHNDipp)(2)E](-) (E = B or Ga) display
      contrasting reactivity towards the half-sandwich titanium imido complex
      Cp*TiCl(NtBu)py; while the gallium system undergoes salt metathesis yielding the
      first example of a titanium gallyl compound, the more nucleophilic boryl anion
      generates a dearomatized pyridyl fragment via attack at the ligand 2-position.

PMID- 20820543
TI  - Methylerythritol cyclodiphosphate (MEcPP) in deoxyxylulose phosphate pathway:
      synthesis from an epoxide and mechanisms.
AB  - In this communication, we reported another unique IspG-catalyzed transformation,
      the production of its substrate, MEcPP, from (2R,3R)-4-hydroxy-3-methyl-2,3
      epoxybutanyl diphosphate (Epoxy-HMBPP) when reductants are excluded from the
      reaction mixture.

PMID- 20820544
TI  - Ultra-fast dye sensitisation and co-sensitisation for dye sensitized solar cells.
AB  - We present a rapid (5 min) and controlled sensitisation method for dye sensitized
      solar cells which gives 6.0% for the Ru dye N719 and 3.7% for the IR absorbing
      squaraine SQ1. Rapid co-sensitization (N719 and SQ1) gives efficiencies up to
      7.9%. Devices have similar or better efficiency to those dyed passively for 18 h.

PMID- 20820545
TI  - Thermosensitive gating effect and selective gas adsorption in a porous
      coordination nanocage.
AB  - A porous coordination nanocage functionalized with 24 triisopropylsilyl groups
      exhibits a remarkable thermosensitive gate opening phenomenon and demonstrates a
      molecular sieving effect at a certain temperature range, which can be used for
      gas separation purposes.

PMID- 20820546
TI  - Selective and efficient magnetic separation of Pb2+ via gold nanoparticle-based
      visual binding enrichment.
AB  - We employed gold nanoparticles to visually enrich lead ions, which led to
      selective magnetic separation with 99% removal efficiency.

PMID- 20820547
TI  - Photoinduced drug release from thermosensitive AuNPs-liposome using a AuNPs
      switch.
AB  - A thermosensitive liposome with embedded AuNPs in a bilayer was prepared using
      supercritical CO(2). The AuNPs-liposome can absorb a certain wavelength light,
      convert optical energy into heat, induce phase transition, and release drug. The
      results show that drug release from the liposome is due to the photothermic
      effects inducing phase transition of the liposome rather than destruction of the
      liposome structure.

PMID- 20820548
TI  - Molecular logic circuit based on a multi-state mononuclear platinum(ii)
      terpyridyl complex.
AB  - A new type of multi-state platinum(ii) terpyridyl acetylide complex: platinum(ii)
      4'-(4-dimethylaminophenyl)-2,2' : 6',2''-terpyridyl ferrocenyl acetylide (1),
      together with its reference complexes: platinum(ii) 4'-(4-methylphenyl)-2,2' :
      6',2''-terpyridyl ferrocenyl acetylide (2), platinum(ii) 4'-(4
      dimethylaminophenyl)-2,2' : 6',2''-terpyridyl phenyl acetylide (3) and
      platinum(ii) 4'-(4-methylphenyl)-2,2' : 6',2''-terpyridyl phenyl acetylide (4),
      are designed and synthesized. UV-vis-NIR absorption and electrochemical studies
      demonstrate that complex 1 possesses three ordered intraligand charge transfer
      (ILCT), ligand-to-ligand charge transfer (LLCT) and metal-to-ligand charge
      transfer (MLCT) states, and the successive modulation of the intramolecular ILCT,
      LLCT and MLCT states in a single mononuclear platinum(ii) complex 1 is well
      evidenced by their reference complexes 2-4. More interestingly, a near-infrared
      absorption band ranging from 720-1000 nm was clearly observed for complexes 1 and
      2 upon oxidation of the sigma-bonded ferrocene-ethynyl group by Fe(ClO(4))(3),
      which was tentatively assigned to platinum(ii)-disturbed ligand-to-metal charge
      transfer (LM'CT) of the ferrocenium group. These promising features allow us to
      integrate the multiple states to reproduce basic logic operations at the
      molecular level. A four-state (LLCT, ILCT, MLCT and LM'CT) molecular switch of
      complex 1 that responds to the stimulation of H(+), Fe(ClO(4))(3) and Zn
      producing four outputs has been encoded in binary digits. The logic function
      executed by complex 1 is equivalent to that of a combinational logic circuit
      integrating seven or eight logic functions as AND, OR, NOT. A three-input-four
      output molecular logic circuit has been established.

PMID- 20820549
TI  - Peroxide and superoxide states of adsorbed O(2) on anatase TiO(2) (101) with
      subsurface defects.
AB  - Density Functional Theory (DFT) calculations within the Generalized Gradient
      Approximation (GGA) and the GGA + U approach are carried out to investigate the
      adsorption of O(2) on anatase (101) surfaces having subsurface oxygen vacancies.
      Our results show that O(2) adsorption is strongly enhanced at sites close to the
      subsurface defect, whereas dissociation is unfavorable at all sites. The
      adsorption is accompanied by the transfer of the defect electrons to O(2)-derived
      electronic states in the anatase surface band gap. Peroxide species (O(2)(2-), O
      O = 1.48 A) are stable when the number of adsorbed O(2) molecules is less or
      equal the number of defects, whereas superoxide species (O(2)(-), O-O = 1.33 A)
      become more favorable at coverages exceeding approximately 1.5 O(2) molecules per
      oxygen vacancy.

PMID- 20820550
TI  - Microfluidic characterization of sustained solute release from porous
      supraparticles.
AB  - We present a novel microfluidic technique for precise characterization of
      controlled release of solute from porous latex supraparticles in a laminar flow
      environment. Dye-infused supraparticles are fabricated via dry self-assembly
      method using droplet templates dispensed on superhydrophobic substrates. A water
      soluble dye is used as a model compound, the release rate of which is measured
      colorimetrically. The sustained release rates of dye from supraparticles and dye
      pellets are quantified and compared to common diffusion/dissolution mass transfer
      models. The results illustrate the potential of microfluidics as a tool in
      monitoring controlled release process and the role of the uniformly porous
      supraparticle matrix for the prolonged continuous solute delivery.

PMID- 20820551
TI  - Morphological tuning, self-assembly and optical properties of indium oxide
      nanocrystals.
AB  - In this paper, weak acids, weak bases or their mixtures were used as reaction
      media/coordinating ligands to achieve systematic morphological control over
      amphoteric indium oxide nanostructures. Different indium/oleic acid molar ratios
      from 1 : 0, 1 : 1, 1 : 2, 1 : 3, 1 : 6 and 1 : 15 in non-coordinating, weakly
      coordinating, strongly coordinating and their mixed media were adopted to prepare
      irregular aggregated nanoparticles and uniform regular/truncated octahedra, etc.
      In addition to their strong size-dependent absorption, single-crystalline indium
      oxide octahedra also gave a strong band-edge emission while irregular indium
      oxide aggregated nanoparticles only exhibited a weak deep-trap emission.
      Meanwhile, the truncated octahedra were self-assembled into either zigzag lines
      or pentagram patterns, and the regular octahedra and truncated cubes were self
      assembled into hexagonally packed nanocrystal arrays. In addition, the formation
      mechanism of the various nanostructures under different conditions was
      investigated in detail.

PMID- 20820552
TI  - (14)N NQR, (1)H NMR and DFT/QTAIM study of hydrogen bonding and polymorphism in
      selected solid 1,3,4-thiadiazole derivatives.
AB  - The 1,3,4-thiadiazole derivatives (2-amino-1,3,4-thiadiazole, acetazolamide,
      sulfamethizole) have been studied experimentally in the solid state by (1)H-(14)N
      NQDR spectroscopy and theoretically by Density Functional Theory (DFT). The
      specific pattern of the intra and intermolecular interactions in 1,3,4
      thiadiazole derivatives is described within the QTAIM (Quantum Theory of Atoms in
      Molecules)/DFT formalism. The results obtained in this work suggest that
      considerable differences in the NQR parameters permit differentiation even
      between specific pure association polymorphic forms and indicate that the
      stronger hydrogen bonds are accompanied by the larger eta and smaller nu(-) and
      e(2)Qq/h values. The degree of pi-electron delocalization within the 1,3,4
      thiadiazole ring and hydrogen bonds is a result of the interplay between the
      substituents and can be easily observed as a change in NQR parameters at N atoms.
      In the absence of X-ray data NQR parameters can clarify the details of
      crystallographic structure revealing information on intermolecular interactions.

PMID- 20820553
TI  - Multilamellar liposomes entrapping aminosilane-modified maghemite nanoparticles:
      "magnetonions".
AB  - 4.6 nm-sized aminosilane-modified maghemite (gamma-Fe(2)O(3)) nanoparticles
      (aMNPs) were synthesized and encapsulated into onion-type multilamellar vesicles
      of soybean phosphatidylcholine (90%mol) and monoolein (10%mol). The magnetic
      multilamellar vesicles were obtained by shearing lipids with an aqueous
      dispersion of the preformed aMNPs (ferrofluid). The influence of ferrofluid
      concentration on the stability of the constitutive lamellar phase and the
      resulting dispersed onions was analyzed by small-angle X-ray diffraction (SAXD)
      and cryo-TEM imaging, respectively. When [Fe(III)] <60 mM, stable, magnetic
      onions were produced with aMNPs inserted inside onion water compartments as
      isolated or aggregated particles. Encapsulation efficiencies were measured by EPR
      spectroscopy and magnetic measurements: much higher values (up to 75%) than
      unilamellar liposomes were found. The deduced aMNP-to-onion ratio increased with
      ferrofluid concentration before reaching a maximal value of ca. 45 as confirmed
      by cryo-TEM imaging. When [Fe(III)] >60 mM, uni- or oligolamellar vesicles in
      addition to onions formed, probably because of a two-phase separation between an
      aMNP-rich phase and an aMNP-containing lamellar phase as revealed by SAXD.

PMID- 20820554
TI  - The importance of fuel dissociation and propargyl + allyl association for the
      formation of benzene in a fuel-rich 1-hexene flame.
AB  - Fuel decomposition and benzene formation processes in a premixed, laminar, low
      pressure, fuel-rich flame of 1-hexene (C(6)H(12), CH(2)=CH-CH(2)-CH(2)-CH(2)
      CH(3)) are investigated by comparing quantitative mole fraction profiles of flame
      species with kinetic modeling results. The premixed flame, which is stabilized on
      a flat-flame burner under a reduced pressure of 30 Torr (= 40 mbar), is analyzed
      by flame-sampling molecular-beam time-of-flight mass spectrometry which uses
      photoionization by tunable vacuum-ultraviolet synchrotron radiation. The
      temperature profile of the flame is measured by OH laser-induced fluorescence.
      The model calculations include the latest rate coefficients for 1-hexene
      decomposition (J. H. Kiefer et al., J. Phys. Chem. A, 2009, 113, 13570) and for
      the propargyl (C(3)H(3)) + allyl (a-C(3)H(5)) reaction (J. A. Miller et al., J.
      Phys. Chem. A, 2010, 114, 4881). The predicted mole fractions as a function of
      distance from the burner are acceptable and often even in very good agreement
      with the experimentally observed profiles, thus allowing an assessment of the
      importance of various fuel decomposition reactions and benzene formation routes.
      The results clearly indicate that in contrast to the normal reactions of fuel
      destruction by radical attack, 1-hexene is destroyed mainly by decomposition via
      unimolecular dissociation forming allyl (a-C(3)H(5)) and n-propyl (n-C(3)H(7)).
      Minor fuel-consumption pathways include H-abstraction reactions producing various
      isomeric C(6)H(11) radicals with subsequent beta-scissions into C(2), C(3), and
      C(4) intermediates. The reaction path analysis also highlights a significant
      contribution through the propargyl (C(3)H(3)) + allyl (a-C(3)H(5)) reaction to
      the formation of benzene. In this flame, benzene is dominantly formed through H
      assisted isomerization of fulvene, which itself is almost exclusively produced by
      the C(3)H(3) + a-C(3)H(5) reaction.

PMID- 20820555
TI  - Interactions of TRIS [tris(hydroxymethyl)aminomethane] and related buffers with
      peptide backbone: thermodynamic characterization.
AB  - In a situation which is far from ideal, many buffers have been found to be quite
      reactive, besides maintaining their stable pH values. On the basis of apparent
      transfer free energies (DeltaG(tr)'), through solubility measurements the
      interactions of zwitterionic glycine peptides: glycine (Gly), diglycine (Gly(2)),
      triglycine (Gly(3)), and tetraglycine (Gly(4)), with several common neutral pH,
      amine-based buffers have been studied. The biological buffers studied in this
      work, including TRIS, TES, TAPS, TAPSO, and TABS are structurally related and all
      contain TRIS groups. These buffers have pK(a) values ranging from 7.5-9.0, which
      allow them to be used in biological, biochemical or environmental studies. We
      observed negative values of DeltaG(tr)' for Gly(3) and Gly(4) from water to
      buffer, indicating that the interactions are favorable. However, the DeltaG(tr)'
      values are positive for Gly and Gly(2), revealing unfavorable interactions, which
      except for the latter in TRIS buffer are negative. The surprising result in our
      data is the unexpected extraordinarily high favorable interactions between TRIS
      buffer and peptides (in comparison with the effect of the most common
      denaturants, urea and guanidine hydrochloride). The transfer free energies
      (DeltaG(tr)') of the peptide backbone unit (-CH(2)C=O-NH-) contributions have
      been estimated from DeltaG(tr)' values. We have also investigated the
      interactions of TRIS buffer with Bovine Serum Albumin (BSA), as a globular
      protein, using dynamic light scattering (DLS), zeta potential, UV-Visible
      absorption, fluorescence and Raman spectroscopy measurements. The results
      indicated that TRIS buffer stabilized the BSA molecules.

PMID- 20820556
TI  - Assessment of noncollinear spin-flip Tamm-Dancoff approximation time-dependent
      density-functional theory for the photochemical ring-opening of oxirane.
AB  - Under the usual assumption of noninteracting v-representability, density
      functional theory (DFT) together with time-dependent DFT (TDDFT) provide a
      formally exact single-reference method suitable for the theoretical description
      of the electronic excited-states of large molecules, and hence for the
      description of excited-state potential energy surfaces important for
      photochemistry. The quality of this single-reference description is limited in
      practice by the need to use approximate exchange-correlation functionals. In
      particular it is far from clear how well approximations used in contemporary
      practical TDDFT calculations can describe funnel regions such as avoided
      crossings and conical intersections. These regions typically involve biradical
      like structures associated with bond breaking and conventional wisdom would seem
      to suggest the need to introduce explicit double excitation character to describe
      these structures. Although this is lacking in ordinary spin-preserving (SP)
      TDDFT, it is present to some extent in spin-flip (SF) TDDFT. We report our tests
      of Wang-Ziegler noncollinear SF-TDDFT within the Tamm-Dancoff approximation for
      describing the avoided crossing in the C(2v) CC ring-opening reaction of oxirane
      and for describing the conical intersection relevant for the more physical
      asymmetric CO ring-opening reaction of oxirane. Comparisons are made with
      complete active space self-consistent field and quantum Monte Carlo benchmark
      results from two previous papers on the subject [J. Chem. Phys., 2007, 127,
      164111; ibid 129, 2008, 124108]. While the avoided crossing in the C(2v) pathway
      is found to be reasonably well described, the method was found to be only
      partially successful for the conical intersection (CX) associated with the
      physically more important asymmetric pathway. The origin of the difficulties
      preventing the noncollinear SF-TDDFT method from giving a completely satisfactory
      description of the CX was traced back to the inability of SF-TDDFT based upon a
      single triplet reference state to correlate all potentially relevant
      configurations involving not just two but three nearly degenerate orbitals (n,
      sigma(CO), and sigma(CO)(*)). This article is also the first report of our
      implementation of SF-TDDFT within the deMon2k program.

PMID- 20820557
TI  - Mesoscopic non-equilibrium thermodynamics of non-isothermal reaction-diffusion.
AB  - We show how the law of mass action can be derived from a thermodynamic basis, in
      the presence of temperature gradients, chemical potential gradients and
      hydrodynamic flow. The solution gives the law of mass action for the forward and
      the reverse contributions to the net chemical reaction. In addition we derive the
      fluctuation-dissipation theorem for the fluctuating contributions to the reaction
      rate, heat flux and mass fluxes. All these results arise without any other
      assumptions than those which are common in mesoscopic non-equilibrium
      thermodynamics; namely quasi-stationary transport across a high activation energy
      barrier, and local equilibrium along the reaction coordinate. Arrhenius-type
      behaviour of the kinetic coefficients is recovered. The thermal conductivity,
      Soret coefficient and diffusivity are significantly influenced by the presence of
      a chemical reaction. We thus demonstrate how chemical reactions can be fully
      reconciled with non-equilibrium thermodynamics.

PMID- 20820558
TI  - Detection of chemical vapors with tunable emission of binary organic nanobelts.
AB  - Tunable emission of binary organic nanobelts was realized via the fluorescence
      resonance energy transfer (FRET) process, which can be exploited for the
      detection of acid and basic chemical vapors.

PMID- 20820559
TI  - Fabrication and surface characterization of single crystal PtBi and PtPb (100)
      and (001) surfaces.
AB  - High quality single crystal PtM (M = Bi or Pb) (100) and (001) surfaces have been
      generated from solid state bulk materials. The specific orientation was
      determined via X-ray Laue back-reflection and the miscut angles of the single
      crystal surfaces were ~0.3 degrees  which was limited by instrumental resolution.
      The PtM (001) electrode had a Pt termination based on cyclic voltammetric (CV)
      profiles. The surface structure and composition of single crystal PtM surfaces
      have been studied by synchrotron-based in situ X-ray grazing incidence
      diffraction (GID) under active electrochemical control. Cycling of the potential
      to increasingly high values resulted in dramatic changes to the surface
      crystalline structure and composition of these single crystal electrodes. Well
      defined Pt nano-domains in a hexagonal pattern with a 23 degrees  offset angle to
      the substrate were formed on the PtM (001) surface after electrochemical
      pretreatment in supporting electrolyte (0.1M H(2)SO(4)), especially for E(ulp)
      (E(ulp) = upper limit potential) of +0.80 V or beyond. From an analysis of the
      diffraction peaks, the size of the Pt domains was estimated to be ~15 nm. The Pt
      domain formation on the single crystal surfaces, similar to results on
      polycrystalline intermetallic phases, was due to leaching of the less-noble
      elements (Bi or Pb) from the intermetallic matrix and sintering of the Pt atoms
      on the surfaces. On the other hand, Pt domains with a preferential direction but
      no offset angle to the substrate were formed on PtM (100) surface after similar
      electrochemical pretreatment. PtBi and PtPb single crystal surfaces exhibited
      different anisotropic electrocatalytic activities towards the electrooxidation of
      formic acid and other potential fuels for fuel cell applications. The
      reactivities of these single crystal electrodes towards the oxidation of small
      organic molecules were a function of E(ulp) values and maximal activities were
      around +0.60 V for PtBi(001) surface which might be due to formation of partially
      oxidized surfaces but around +1.20 V for PtPb(100) and (001) surfaces which might
      be due to the increasing boundary lines of Pt and PtPb grains.

PMID- 20820560
TI  - Sublimation of the endohedral fullerene Er(3)N@C(80).
AB  - The heat of sublimation of the endohedral metallofullerene Er(3)N@C(80) was
      measured via Knudsen effusion mass spectrometry. The large molecule consists of a
      C(80) fullerene cage which is stabilized by a complex of three erbium atoms
      bounded to a nitrogen atom and has a mass of 1475 amu. The mass spectrum at a
      temperature of 1045 K and the relative intensities of the thermal fractions of
      Er(3)N@C(80) are provided. We also discuss possible thermal decomposition
      processes for these particles. By measuring the quantity of evaporated molecules
      in thermal equilibrium using a quadrupole mass spectrometer in a temperature
      range between 782 K and 1128 K, a value for the sublimation enthalpy of
      DeltaH(sub) = 237 +/- 7 kJ mol(-1) is obtained via the second-law method.

PMID- 20820561
TI  - Quantification of H(2)O(2) concentrations in aqueous solutions by means of
      combined NMR and pH measurements.
AB  - The NMR transverse relaxation time T(2), determined by a CPMG multipulse
      sequence, of aqueous hydrogen peroxide (H(2)O(2)) solutions strongly depends on
      the rate of exchange of the spin-bearing protons between the H(2)O(2) and H(2)O
      molecules. For pulse separations exceeding the inverse exchange rate, this value
      becomes a constant only depending on proton exchange time and magnetic field
      strength. Since this exchange time depends in a non-analytical way on the
      concentration of H(2)O(2) and on the pH value, a measurement of T(2) and pH
      allows the inversion of the data for the non-invasive determination of the
      H(2)O(2) concentration. The generation of calibration data for a range of
      concentrations and pH values is presented and is applied to a heterogeneously
      catalyzed H(2)O(2) decomposition involving commercial catalyst pellets. The
      evolution of the concentration during the course of reactions is monitored and
      the long-time deactivation of the pellet is demonstrated using this technique.
      The method is suggested as a means for contact-free and non-invasive on-line
      monitoring of H(2)O(2) concentrations.

PMID- 20820563
TI  - Facile approaches to build ordered amphiphilic tris(phthalocyaninato) europium
      triple-decker complex thin films and their comparative performances in ozone
      sensing.
AB  - Solution processed thin films of an amphiphilic tris(phthalocyaninato) rare earth
      triple-decker complex, Eu(2)[Pc(15C5)(4)](2)[Pc(OC(10)H(21))(8)], have been
      prepared from three different methods: self-assembly (SA) annealed in solvent
      vapor, quasi-Langmuir-Shafer (QLS) and drop casting methods. In particular, we
      successfully developed a simple QLS process for fabricating ordered multilayers
      with a good thickness control. The films prepared from three different methods
      were characterized by a wide range of methods including electronic absorption
      spectra, IR, X-ray diffraction, atomic force microscopy (AFM), and current
      voltage (I-V) measurements. J-type aggregates have been formed with the
      increasing degree of order of molecular stacking Cast < QLS < SA films. Moreover,
      the gas sensing behavior of the three types of films was investigated towards
      ozone in the 8-300 ppb range. Unexpectedly good sensitive, stable and
      reproducible responses to O(3) gas are obtained for these kinds of ultra-thin
      solution processed films in a fast response/recovery cycle of only 1/4 min. The
      response of Eu(2)[Pc(15C5)(4)](2)[Pc(OC(10)H(21))(8)] films is linearly
      correlated to the ozone concentration. The interaction between the
      Eu(2)[Pc(15C5)(4)](2)[Pc(OC(10)H(21))(8)] films and different ozone
      concentrations was found to follow first-order kinetics. Strikingly, QLS films
      showed the most stable response and the largest average sensor response rate
      constant among the three types of films.

PMID- 20820562
TI  - Influence of KCl on the interfacial activity and conformation of hemoglobin
      studied by Langmuir-Blodgett technique.
AB  - We report here the influence of KCl on the interfacial surface activity and
      conformation of human adult hemoglobin (Hb) using Langmuir and Langmuir-Blodgett
      (LB) techniques. The studies were done in absence and in presence of KCl salt in
      the subphase. We have studied the surface pressure-area (pi-A) isotherm and
      surface pressure-time (pi-t) kinetics of Hb with the variation of KCl
      concentrations (C(KCl)). The pi-t study shows that the surface activity as well
      as the magnitude of diffusion and rearrangement of Hb at air/water interface is a
      function of C(KCl). Conformational study was done by CD spectroscopy and by the
      FTIR technique. Both the studies show an increasing trend of the alpha-helix form
      of Hb in the presence of KCl which may be responsible for the increased surface
      activity of Hb. The free energy calculations show that the compression of the Hb
      monolayer is involved in the small free energy change (~5-25 kcal mol(-1)) of Hb.
      The changes in area per molecule and free energy, as well as other results,
      indicate that the influence of KCl on the Hb monolayer is in line with modified
      DLVO theory of ion-protein interaction. FE-SEM study shows that the LB films in
      absence of KCl comprise higher aggregates, whereas in the presence of KCl (0.5 M)
      it comprises lower aggregates, indicating the structural change of Hb. KCl salt
      here enhances the alpha-helix from of Hb, promoting the folded conformation by
      perturbing the water structure. The overall results show that the intermolecular
      forces and the surface activity as well as the population of the alpha-helix of
      Hb can be tuned by KCl salt.

PMID- 20820564
TI  - Nitrate radical addition-elimination reactions of atmospherically relevant sulfur
      containing molecules.
AB  - We have used different computational methods, including B3LYP, CCSD(T)-F12 and
      CBS-QB3, to study and compare the addition-elimination reaction of the nitrate
      radical NO(3) with four sulfur-containing species relevant to atmospheric
      chemistry: hydrogen sulfide (H(2)S), dimethyl sulfide [(CH(3))(2)S], dimethyl
      sulfoxide [(CH(3))(2)SO] and sulfur dioxide (SO(2)). We find that the reaction
      with (CH(3))(2)SO to give NO(2) + (CH(3))(2)SO(2) has a very low barrier, and is
      likely to be the dominant oxidation mechanism for (CH(3))(2)SO in the atmosphere.
      In agreement with previous experimental data and computational results, we find
      that the reaction with H(2)S and SO(2) is very slow, and the reaction with
      (CH(3))(2)S is not competitive with the hydrogen abstraction route. The
      differences in reaction energetics and rates between the four species are
      explained in terms of stabilizing interactions in the transition states and
      differences in sulfur-oxygen bond strengths.

PMID- 20820565
TI  - Synergy effect of nanostructure electrodes supported by tungsten carbide and
      oxide for methanol electrooxidation.
AB  - We report nanostructure electrodes for methanol electrooxidation by means of the
      co-sputtering deposition method. The Pt-WC-WO(3) three-phase electrode has higher
      I(f)/I(b) and oxidation current density i.e. improved electrocatalytic activity
      in comparison with those of pure Pt and two-phase electrodes because of both
      catalysis of tungsten carbide and size-control by tungsten oxide.

PMID- 20820566
TI  - Transverse piezoelectric field-effect transistor based on single ZnO nanobelts.
AB  - A transverse piezoelectric field-effect transistor (TP-FET) based on single ZnO
      nanobelts has been fabricated on a metallic graphite substrate in an atomic force
      microscope (AFM). The source-to-drain current of the TP-FET was found to decrease
      with increasing loading force under a positive bias due to the carrier-trapping
      effect and the creation of a charge-depletion zone. This TP-FET can be applied as
      a force/pressure sensor for measuring nanoNewton forces ranged from 0 to 700 nN.

PMID- 20820567
TI  - CCl(4) dissociation on the ice I(h) surface: an excess electron mediated process.
AB  - Dissociation of chlorofluorocarbons in the atmosphere is a heterogeneous process
      that takes place mainly on the surface of ice particles. Recently an enhancement
      of the dissociation rate due to excess electrons has been shown theoretically and
      correspondingly measured experimentally. Our density functional theory
      calculations show that CCl(4) dissociates due to an excess electron with an
      energy gain of 0.8 eV on the ice surface as opposed to in the gas phase. Through
      the use of ab initio molecular dynamics, an atomistic pathway for this
      dissociation has been elucidated, this pathway shows the capture of Cl(-) by the
      ice surface through a partial solvation mechanism, in agreement with recent
      experimental findings.

PMID- 20820568
TI  - Competing ultrafast photoinduced quenching reactions in cinnamic acid : peptide
      blends.
AB  - This report focuses on the ultrafast photoinduced excited state dynamics of
      cinnamic acid : peptide blends, prototypical MALDI samples. We prepared thin
      homogeneous layers of closely spaced microcrystals using alpha-cyano-4
      hydroxycinnamic acid (alpha-CHC) and sinapinic acid (SA) as cinnamic acid (CA)
      derivatives and Angiotensin II (Ang II) as peptide. We applied spectrally and
      temporally resolved photoluminescence (PL) spectroscopy and identified in these
      blends different ultrafast and strongly competing PL quenching mechanisms. [2+2]
      Photodimerization is a known ultrafast solid-state photoreaction in CA crystals.
      We show that-after sufficient illumination times-it also governs the PL dynamics
      of CA : peptide blends. In addition, the peptide admixture induces a new PL
      quenching pathway, which proceeds most probably via photoisomerization or via
      energy transfer to stereoisomers at the CA : peptide interface, i.e., at disorder
      sites inside the microcrystals or at their surface. For alpha-CHC : Ang II
      blends, we find a photodimerization rate of (20 ps)(-1) and a quenching rate
      coefficient of 2.67 * 10(15) s(-1) mol(-1) cm(3) when adding the Ang II peptide.
      For SA : Ang II blends, the corresponding rates are even faster but the more
      remarkable feature is that the PL of the photoproduced stereoisomers is in turn
      quenched with increasing illumination time by the growing number of photodimers.
      Both photodimerization and peptide-induced quenching are obviously fast enough to
      compete with singlet-singlet annihilations even at typical MALDI fluences. We
      suggest that photoinduced ultrafast changes of the crystalline or molecular
      structure play a substantial role for the release of large molecular ions from
      MALDI substrates and are a common feature for UV-MALDI.

PMID- 20820569
TI  - Effects of potential shift and efficiency of charge collection on nanotube-based
      porphyrin-sensitized solar cells with conjugated links of varied length.
AB  - For dye-sensitized solar-cell devices fabricated from porphyrin sensitizers with
      links of varied length (PE1-PE4) adsorbed on anodic titanium-oxide nanotube
      arrays, we measured induced photocurrent and photovoltage decays under constant
      bias illumination; the evaluated efficiencies of charge collection of the devices
      show a systematic trend PE4 > PE3 > PE2 > PE1 at a large short-circuit current,
      implying that a long link would improve the charge separation if the electrons
      were effectively injected into the semiconductor.

PMID- 20820570
TI  - Hydrolysis of tetravalent group IV metal ions: an ab initio simulation study.
AB  - Simulations of the tetravalent group IV metal ions, Ge(IV), Sn(IV), and Pb(IV),
      in aqueous solution were performed using ab initio quantum mechanical charge
      field molecular dynamics (QMCF MD). The process of hydrolysis, which occurred for
      each of the metal ions, was analyzed in terms of the time evolution of solvent
      configuration. Several important factors involved in the initiation of proton
      dissociation from first shell water molecules are discussed in connection to the
      nature of proton mobility in aqueous solution.

PMID- 20820571
TI  - Coherence resonances in an excitable thermochemical system with multiple
      stationary states.
AB  - A master equation approach is used to study the influence of internal
      fluctuations on the dynamics of three excitable thermochemical systems exhibiting
      continuous as well as discrete changes of temperature. The systems differ by the
      types of excitability. The dependences of the relative deviations from mean
      values of the interspike intervals and escape times from the stable stationary
      state on the size of the systems calculated from simulations of stochastic
      trajectories exhibit minima, which testify to the appearance of resonance
      phenomena. An explanation for the appearance of the stochastic resonances is
      presented.

PMID- 20820572
TI  - The potential of AB(1Phi) systems for direct actinometry. Diarylethenes as
      successful actinometers for the visible range.
AB  - A new actinometric procedure based on the analysis of kinetic traces of the
      actinometer is proposed in this study. It is suitable for thermally-stable
      photochromes, such as diaryethenes, which may be useful candidates for visible
      range actinometry. The treatment of the traces employs a rate law which was
      achieved via the closed-form integration of the differential equation describing
      the kinetics of unimolecular photoreactions (i.e. an initial species A converted
      into a photoproduct B, AB(1Phi)), subjected to monochromatic irradiation. The
      advantage of the present method is that it may allow the development of reliable
      actinometers without the need for prior knowledge of some important reaction
      attributes, namely, the absolute values of the photoreaction quantum yield, the
      concentration and the molar absorption coefficient of the actinometric species at
      the irradiation wavelength or their variation with irradiation. This method has
      been tested against both kinetic data obtained from Runge-Kutta calculations and
      experimental traces of a diarylethene derivative. The usefulness of this
      derivative for actinometry has been studied in the visible (405-570 nm) spectral
      range. It has also been shown that the procedure can be applied to individual
      measurements from steady-state experiments and it is able to identify and
      overcome quantum yield variability with irradiation wavelength. This method is
      expected to help recruit AB(1Phi) photochromes for actinometry with the aim of
      extending their operative range over the entire visible region.

PMID- 20820573
TI  - N-H...F hydrogen bonds in fluorinated benzanilides: NMR and DFT study.
AB  - Using (19)F and (1)H-NMR (with (14)N decoupling) spectroscopic techniques
      together with density functional theoretical (DFT) calculations, we have
      investigated weak molecular interactions in isomeric fluorinated benzanilides.
      Simultaneous presence of through space nuclear spin-spin couplings ((1h)J(N-HF))
      of diverse strengths and feeble structural fluctuations are detected as a
      function of site specific substitution of fluorine atoms within the basic
      identical molecular framework. The transfer of hydrogen bonding interaction
      energies through space is established by perturbing their strengths and
      monitoring the effect on NMR parameters. Multiple quantum (MQ) excitation, up to
      the highest possible MQ orders of coupled protons, is utilized as a tool for
      accurate (1)H assignments. Results of NMR studies and DFT calculations are
      compared with the relevant structural parameters taken from single crystal X-ray
      diffraction studies.

PMID- 20820574
TI  - Chiral supramolecular self-assembly of rubrene.
AB  - Large area chiral supramolecular self-assembly of rubrene has been achieved on
      Au(111) surface at room temperature. The basic building block of such self
      assembled layers consists of two double-layered Y-shape supramolecular structures
      containing eight twisted rubrene molecules. Chirality is maintained and
      transferred from the bottom layer to the top layer in the successive molecular
      layers for up to five layers. Such chiral multilayers can be potential candidates
      in enantioselective catalysis and chiral separations.

PMID- 20820575
TI  - Ultrafast inter- and intramolecular vibrational energy transfer between molecules
      at interfaces studied by time- and polarization-resolved SFG spectroscopy.
AB  - We present experimental results on femtosecond time-resolved surface vibrational
      spectroscopy aimed at elucidating the sub-picosecond reorientational dynamics of
      surface molecules. The approach, which relies on polarization- and time-resolved
      surface sum frequency generation (SFG), provides a general means to monitor
      interfacial reorientational dynamics through vibrations inherent in surface
      molecules in their electronic ground state. The technique requires an anisotropic
      vibrational excitation of surface molecules using orthogonally polarized infrared
      excitation light. The decay of the resulting anisotropy is followed in real-time.
      We employ the technique to reveal the reorientational dynamics of vibrational
      transition dipoles of long-chain primary alcohols on the water surface, and of
      water molecules at the water-air interface. The results demonstrate that, in
      addition to reorientational motion of specific molecules or molecular groups at
      the interface, inter- and intramolecular energy transfer processes can serve to
      scramble the initial anisotropy very efficiently. In the two exemplary cases
      demonstrated here, energy transfer occurs much faster than reorientational motion
      of interfacial molecules. This has important implications for the interpretation
      of static SFG spectra. Finally, we suggest experimental schemes and strategies to
      decouple effects resulting from energy transfer from those associated with
      surface molecular motion.

PMID- 20820576
TI  - Model anodes and anode models for understanding the mechanism of hydrogen
      oxidation in solid oxide fuel cells.
AB  - This article presents a literature review and new results on experimental and
      theoretical investigations of the electrochemistry of solid oxide fuel cell
      (SOFC) model anodes, focusing on the nickel/yttria-stabilized zirconia (Ni/YSZ)
      materials system with operation under H(2)/H(2)O atmospheres. Micropatterned
      model anodes were used for electrochemical characterization under well-defined
      operating conditions. Structural and chemical integrity was confirmed by ex situ
      pre-test and post-test microstructural and chemical analysis. Elementary kinetic
      models of reaction and transport processes were used to assess reaction pathways
      and rate-determining steps. The comparison of experimental and simulated
      electrochemical behaviors of pattern anodes shows quantitative agreement over a
      wide range of operating conditions (p(H(2)) = 8*10(2) - 9*10(4) Pa, p(H(2)O) =
      2*10(1) - 6*10(4) Pa, T = 400-800  degrees C). Previously published experimental
      data on model anodes show a strong scatter in electrochemical performance.
      Furthermore, model anodes exhibit a pronounced dynamics on multiple time scales
      which is not reproduced in state-of-the-art models and which is also not observed
      in technical cermet anodes. Potential origin of these effects as well as
      consequences for further steps in model anode and anode model studies are
      discussed.

PMID- 20820577
TI  - Electron capture induced dissociation of dipeptide dications: where does the
      charge go?
AB  - Charge partitioning after electron capture induced dissociation of dipeptide
      dications is determined by proton mobility in the evanescent ion-molecule complex
      as the remaining proton has enough time to choose the fragment with the highest
      proton affinity.

PMID- 20820578
TI  - Influence of urea and guanidine hydrochloride on lysozyme stability and thermal
      denaturation; a correlation between activity, protein dynamics and conformational
      changes.
AB  - The effect of urea and guanidine hydrochloride (GuHCl) on lysozyme stability has
      been investigated using activity measurements, microcalorimetry and Raman
      spectroscopy in the low-frequency and amide I regions. Raman investigations on
      lysozyme dissolved in H(2)O and D(2)O in the presence of up to 10 M denaturants
      have revealed direct binding between the protein and both denaturants. The
      analysis of isotopic exchanges in the amide I region allows the identification of
      binding sites as hydrophilic and hydrophobic groups, respectively, for urea and
      GuHCl. The weak loss of activity of lysozyme in the presence of urea (~15%
      maximum) is mainly assigned to a transformation of the tertiary structure
      corresponding to a molten globule state without unfolding of alpha-helix
      structures, in contrast to GuHCl which clearly induces conformational changes,
      associated with a larger loss of activity (40% maximum). The denaturing power of
      urea and guanidine hydrochloride on lysozyme has been related to the solvent and
      protein dynamics, reflecting direct interaction between denaturants and protein.
      It clearly appears that solvent dynamics control protein dynamics, and the
      significant hardening of the dynamics of GuHCl aqueous solutions is considered
      responsible for its important denaturing power. The comparison between the low
      frequency spectra of solvents and lysozyme aqueous solutions in the absence and
      presence of different types of additives (urea, GuHCl, trehalose) reveals the
      Raman signature of the hydration water dynamics. This comparison points out the
      exclusion of trehalose around the protein surface.

PMID- 20820579
TI  - Photocatalytic hydrogen evolution on dye-sensitized mesoporous carbon nitride
      photocatalyst with magnesium phthalocyanine.
AB  - Spectral sensitization of a mesoporous graphite carbon nitride (mpg-C(3)N(4))
      photocatalyst was investigated by depositing magnesium phthalocyanine (MgPc) to
      expand the absorption to wavelengths longer than those of the principal mpg
      C(3)N(4). The obtained sample, MgPc/Pt/mpg-C(3)N(4) (Pt as a cocatalyst) showed
      stable photocatalytic evolution of hydrogen from aqueous solution in the presence
      of sacrificial reagents (triethanolamine), even under irradiation at wavelengths
      longer than 600 nm. Increasing the amount of MgPc led to ordered MgPc aggregation
      on the photocatalyst surfaces. The rate of photocatalytic hydrogen evolution was
      highest on a sample with an amount of MgPc corresponding to a monolayer on the
      Pt/mpg-C(3)N(4) photocatalyst surface. The obtained action spectra of hydrogen
      evolution and the observation that the amount of evolved hydrogen substantially
      surpassed the amount of MgPc, confirm that the introduced MgPc functioned as a
      photocatalytic sensitizer.

PMID- 20820581
TI  - Computational study of lanthanide(III) hydration.
AB  - Lanthanide(iii) hydration was studied by utilizing density-functional theory and
      second-order Moller-Plesset perturbation theory combined with scalar-relativistic
      4f-in-core pseudopotentials and valence-only basis sets for the Ln(iii) ions. For
      [Ln(iii)(H(2)O)(h)](3+) (h = 7, 8, 9) and [Ln(iii)(H(2)O)(h-1).H(2)O](3+) (h = 8,
      9) molecular structures, binding energies, entropies and energies of hydration as
      well as Gibbs free energies of hydration were calculated using
      (8s7p6d3f2g)/[6s5p5d3f2g] basis sets for Ln(iii) and aug-cc-pV(D,T)Z basis sets
      for O and H in combination with the COSMO solvation model. At the generalized
      gradient approximation level of density-functional theory a preferred hydration
      number of 8 is found for La(iii)-Tm(iii) and 7 for Yb(iii)-Lu(iii), whereas
      hybrid density-functional theory predicts a hydration number 8 for all Ln(iii).
      At the SCS-MP2 level of theory the preferred hydration number is found to be 9
      for La(iii)-Sm(iii) and 8 for Eu(iii)-Lu(iii) in good agreement with experimental
      evidence.

PMID- 20820580
TI  - Electron transfer reaction of light harvesting zinc naphthalocyanine
      subphthalocyanine self-assembled dyad: spectroscopic, electrochemical,
      computational, and photochemical studies.
AB  - Electron transfer reaction of a self-assembled donor-acceptor dyad formed by
      axial coordination of zinc naphthalocyanine, ZnNc, and subphthalocyanine appended
      with pyridine coordinating ligand, SubPc(py), was investigated in the present
      study. The SubPc(Py) : ZnNc self-assembled dyad absorbs the light in a wide
      section of the UV/Vis/NIR spectra. The formation constant of SubPc(py) : ZnNc in
      o-dichlorobenzene was found to be 1.2 * 10(5) M(-1) from the steady-state
      absorption and emission measurements, suggesting stable complex formation. The
      geometric and electronic calculations by using ab initio B3LYP/6-311G methods
      showed the majority of the highest occupied frontier molecular orbital (HOMO) on
      the zinc naphthalocyanine entity, while the lowest unoccupied molecular orbital
      (LUMO) was on the subphthalocyanine entity, suggesting that the charge-separated
      state of the supramolecular complex is (SubPc(py))(-) : ZnNc(+). The
      electrochemical results suggest the exothermic charge-separation process via the
      singlet states of both SubPc(py) and ZnNc entities. Upon coordination the
      pyridine appended subphthalocyanine to ZnNc; the main quenching pathway involved
      charge separation via the singlet excited states of ZnNc and SubPc(py). A clear
      evidence of the intramolecular electron transfer from the singlet state of ZnNc
      to SubPc(py) was monitored by femtosecond laser photolysis in o-dichlorobenzene
      by observing the characteristic absorption band of the ZnNc radical cation in the
      NIR region at 960 nm. The rate of charge-separation process was found to be 1.3 *
      10(10) s(-1), indicating fast and efficient charge separation. The rate of charge
      recombination and the lifetime of the charge-separated state were found to be 1.0
      * 10(9) s(-1) and 1 ns, respectively. The absorption in a wide section of the
      solar spectrum and high charge-separation/charge-recombination ratio suggests the
      usefulness of self-assembled SubPc(Py) : ZnNc for being a photosynthetic model.

PMID- 20820582
TI  - A density functional theory study on ligand additive effects on redox potentials.
AB  - Adiabatic energy differences DeltaE(adiabatic) are computed at density functional
      theory (DFT) level for the oxidation half reaction of [M(CO)(n)L(6-n)] complexes
      (M = Ru(2+/3+), Os(2+/3+), Tc(2+/3+); L = CN(-), Cl(-), water, CH(3)CN, N(2) and
      CO). Linear trends in DeltaE(adiabatic) with respect to the substitution number
      n(CO) support the hypothesis of additive ligand effects on the redox potential.
      The values of the slope of these linear regression curves are shown to be
      independent of metal type (Ru, Os and Tc) and can therefore act as a ligand
      specific parameter. Based on these parameters, a computed electrochemical series
      was constructed, which was in good agreement with Pickett's P(L), Lever E(L)(L)
      and CEP parameters. The linearity in DeltaE(adiabatic) is also reflected in the
      structural properties such as the M-CO bond distances of [M(CO)(n)L(6-n)]
      complexes. An energy decomposition analysis of the bond between the metal
      fragment and ligand gave an additional insight into the ligand's bonding
      properties in terms of electrostatic and orbital contributions.

PMID- 20820583
TI  - The transfer of neutral molecules, ions and ionic species from water to wet
      octanol.
AB  - Partition coefficients for transfer from water to wet octanol have been set out
      for permanent ions, and for ionic species derived from neutral molecules by loss
      or acceptance of a proton. A previous equation for the partition of neutral
      compounds from water to wet octanol has been extended to include the partition of
      permanent ions, and ionic species; the only additional descriptors required are
      J(+) for cations and J(-) for anions. Fourteen cations and twelve anions are
      included in the equation. It is shown that differences in partition coefficients
      between neutral species and the corresponding ionic species, as log P(oct), are
      not at all constant. For carboxylic acids and the corresponding anion,
      differences are about 5.0 log units, for phenols and the corresponding anion
      differences range from 2.2 to 4.9 log units, and for amines and the corresponding
      protonated cations there is an enormous range of differences from 0.6 to 7.1 log
      units.

PMID- 20820584
TI  - Interfacial charge transfer dynamics in CdSe/dipole molecules coated quantum dot
      polymer blends.
AB  - We report our results on the influence of the dipole moment of small molecules
      anchored to the surface of CdSe nanocrystals, over the interfacial charge
      recombination dynamics in CdSe/P3HT (P3HT : poly-3-hexylthiophene). The
      polarizability of the CdSe/P3HT interface is key to achieving efficient charge
      separation and slow back electron transfer, two of the most important processes
      to boost the photocurrent and voltage in CdSe/P3HT photovoltaic devices.

PMID- 20820585
TI  - Stabilizing metal nanoparticles for heterogeneous catalysis.
AB  - Metal nanoparticles hold great promise for heterogeneous catalysis due to their
      high dispersion, large concentration of highly undercoordinated surface sites,
      and the presence of quantum confinement effects, which can drastically alter
      their reactivity. However, the poor thermal stability of nano-sized particles
      limits their use to low temperature conditions and constitutes one of the key
      hurdles towards industrial application. The present perspective paper briefly
      reviews the mechanisms underlying nanoparticle sintering, and then gives an
      overview of emerging approaches towards stabilizing metal nanoparticles for
      heterogeneous catalysis. We conclude by highlighting the current needs for
      further developments in the field.

PMID- 20820586
TI  - Photodissociation of group-6 hexacarbonyls: observation of coherent oscillations
      in an antisymmetric (pseudorotation) vibration in Mo(CO)(5) and W(CO)(5).
AB  - On dissociation of M(CO)(6), M = Cr, Mo and W, by a femtosecond UV laser (<270 to
      360 nm), pronounced coherent oscillations are observed in the pentacarbonyl
      products on probing by long-wavelength (810 nm) ionization in the gas phase. They
      are vibrations in the ground state, driven by the slope from a conical
      intersection on relaxation from the initially formed excited state (S(1)).
      Surprisingly, with M = Mo and W we also find a fundamental of an antisymmetric
      (b(2) in C(4v)) vibration. From positive and negative displacements along such a
      coordinate one would expect the same signal, so that there should be only
      overtones. Vibrational selection rules are therefore considered for time-resolved
      spectroscopy. The reason for the symmetry breaking is suggested to result from
      the fact that the phase in superposition of wave functions is established by the
      pump process and this phase is conserved in probing, independently of the probe
      delay. An antisymmetric fundamental can be observed, if there is a small
      tunneling splitting in a state involved in the probe process. The observations
      also imply some conclusions on the dissociation and relaxation processes and the
      potentials: with longer wavelengths, the wave packet enters on the same surface
      but from a different direction to S(1). Only a very minor fraction of the
      available energy appears as coherent oscillation. There is no equipartition at
      the end, and a second CO is cleaved off in few picoseconds, even if there is only
      very little excess energy. Triplets do not contribute, even in the tungsten
      system and at longest wavelengths. The dissociation mechanism involves passage of
      the wave packet from all initial states over an avoided crossing to a repulsive
      ligand-field surface. It predicts that in some other molecules, the barrier
      caused thereby is larger and for long photolysis wavelength the lifetime is long
      enough for intersystem crossing to take place; it also predicts wavelength
      dependences in these cases. It is again emphasized that there is no vertical
      internal conversion; instead, the molecule is controlled by slopes and
      intersections of potentials. Also lifetimes can be considered as a control
      parameter in photochemistry.

PMID- 20820588
TI  - Boron K4 crystal: a stable chiral three-dimensional sp(2) network.
AB  - Based on first-principles equation-of-state and lattice dynamics calculations, a
      new boron allotrope with K(4) structure is proposed, which gives the first
      example of a three-dimensional all sp(2) network.

PMID- 20820587
TI  - ATP synthases: cellular nanomotors characterized by LILBID mass spectrometry.
AB  - Mass spectrometry of membrane protein complexes is still a methodological
      challenge due to hydrophobic and hydrophilic parts of the species and the fact
      that all subunits are bound non-covalently together. The present study with the
      novel laser induced liquid bead ion desorption mass spectrometry (LILBID-MS)
      reports on the determination of the subunit composition of the F(1)F(o)-ATP
      synthase from Bacillus pseudofirmus OF4, that of both bovine heart and, for the
      first time, of human heart mitochondrial F(1)F(o)-ATP synthases. Under selected
      buffer conditions the mass of the intact F(1)F(o)-ATP synthase of B. pseudofirmus
      OF4 could be measured, allowing the analysis of complex subunit stoichiometry.
      The agreement with theoretical masses derived from sequence databases is very
      good. A comparison of the ATP synthase subunit composition of 5 different ATPases
      reveals differences in the complexity of eukaryotic and bacterial ATP synthases.
      However, whereas the overall construction of eukaryotic enzymes is more complex
      than the bacterial ones, functionally important subunits are conserved among all
      ATPases.

PMID- 20820589
TI  - Nanoporous gold: a new material for catalytic and sensor applications.
AB  - Nanostructured materials are governed by their surface chemical properties. This
      is strikingly reflected by np-Au. This material can be generated by corrosion of
      bulk Ag-Au alloys. Based on a self-organisation process, a 3 dimensional sponge
      like gold structure evolves with ligaments in the range of only a few tens of
      nanometers. Due to its continuous porosity, the material can be penetrated by
      gases which then adsorb and interact with the surface. In this perspective we
      will review potential applications of np-Au resulting from this effect, namely
      heterogeneous gas phase catalysis, surface chemistry driven actuation, and
      adsorbate controlled stability of the nanostructure. We will summarize the
      current knowledge about the low temperature oxidation of CO as well as the highly
      selective oxidation of methanol. Furthermore, we will address the question how
      surface chemistry can influence the material properties itself. In particular, we
      will deal with (a) the actuation of np-Au by the reversible oxidation of its
      surface using ozone and (b) the adsorbate controlled coarsening of ligaments,
      using annealing experiments under ozone or inert gas atmosphere.

PMID- 20820590
TI  - Hydrogen bonding in electronically excited states: a comparison between formic
      acid dimer and its mono-substituted thioderivatives.
AB  - A multi-state complete active space second order perturbation theory (MS-CASPT2)
      study on the valence singlet electronic excited states of formic acid dimer is
      presented. The electronic spectrum of this dihydrogen bonded system is dominated
      by npi* and pipi* intramonomer and charge transfer excitations and consists of a
      very intense pipi* transition at 8.25 eV and three weaker npi*(2*) and pipi*(1*)
      electronic excitations at 6.21 eV, 9.13 eV, and 9.93 eV, respectively. The
      characteristic npi*-npi*-pipi*-pipi*... pattern found in the formic acid dimer
      electronic spectrum is altered when a sulfur atom is introduced in the molecule.
      Furthermore, carbonyl-by-thiocarbonyl or hydroxyl-by-thiohydroxyl substitution is
      predicted to strongly affect the intensity of the above electronic transitions.
      The effect of oxygen-by-sulfur substitution on the geometry of the first excited
      state (S(1)) has been investigated at the CC2 and CASSCF levels of theory.
      Although the two methods qualitatively predict the same geometrical changes upon
      npi* excitation, the geometries of the S(1) state are found to differ
      considerably between the two levels.

PMID- 20820591
TI  - Cationized phenylalanine conformations characterized by IRMPD and computation for
      singly and doubly charged ions.
AB  - Electrospray ionization produces phenylalanine (Phe) complexes of the alkali
      metal ion series, plus Ag(+) and Ba(2+). Infrared multiple photon dissociation
      (IRMPD) spectroscopy using the FELIX free electron laser light source is used to
      characterize the conformations of the ions, in conjunction with density
      functional theory (DFT) calculations giving thermochemical information and
      computed infrared spectra for likely candidate conformations. For complexes of
      small, singly charged ions (Li(+), Na(+), K(+) and Ag(+)) a single tridentate,
      charge-solvated conformational theme (N/O/Ring) binding amino nitrogen, carbonyl
      oxygen and the aromatic ring to the metal ion accounts for all the observations.
      The larger alkalis Rb(+) and Cs(+) show clear spectroscopic evidence of mixed
      populations, containing substantial fractions of both tridentate and also
      bidentate chelation. For Rb(+) the bidentate fraction is assigned as the (O/Ring)
      chelation pattern, while for Cs(+) a mixture of (O/Ring) and (O/O) chelation
      patterns seems likely. All of the smaller ions with high positive charge density
      have a clear preference for cation-pi interaction with the side-chain aromatic
      ring, but for the larger ions Rb(+) and particularly Cs(+) this interaction
      becomes sufficiently weak to allow conformations having the metal ion remote from
      the pi system. The Ba(2+) complex is unique in showing clear evidence of a major
      fraction of salt-bridge (zwitterionic) ions along with charge-solvated
      conformations. Plots of the frequency shifts of the two highly perturbed ligand
      vibrational modes (C[double bond, length as m-dash]O stretch and NH(2) frustrated
      inversion) give good linear correlations with the binding energy of the metal to
      the ligand.

PMID- 20820592
TI  - BaCO3 mesocrystals: new morphologies using peptide-polymer conjugates as
      crystallization modifiers.
AB  - Nanocrystal superstructures of barium carbonate (BaCO(3)) which exhibit unusual
      morphologies are obtained by the carbon dioxide vapor diffusion technique in the
      presence of poly(ethylene oxide)-block-eicosa aspartate (PEO-b-Asp(20)). The
      highly effective bioconjugate acts as a crystal growth modifier over a broad
      range of concentrations. Instead of commonly observed branched needles, the
      morphology can be systematically varied along different twinned growth patterns
      towards well-defined branched dumbbells. Detailed analysis of the crystal
      substructures with high resolution scanning electron microscopy (HRSEM) and
      dynamic light scattering (DLS) discloses a potential growth mechanism of the
      superstructures and reveals the role of the polymeric bioconjugate therein.

PMID- 20820593
TI  - Effect of the surface on the secondary structure of soft landed peptide ions.
AB  - Ion soft landing (SL) enables highly selective modification of substrates for
      applications in materials science, nanotechnology and biology. Our previous study
      [P. Wang and J. Laskin, Angew. Chem., Int. Ed., 2008, 47, 6678-6680] showed that
      SL can be used for preparation of conformation-selected peptide arrays. Here we
      present a first study of the effect of the surface on the secondary structures of
      peptides soft-landed onto self-assembled monolayer surfaces (SAMs). Conformations
      of soft-landed peptide ions were examined using a newly constructed instrument
      that enables in situ infrared reflection absorption spectroscopy (IRRAS)
      characterization of surfaces during and after ion deposition. Polyalanine
      peptides, Ac-A(n)K and Ac-KA(n) (n = 7, 15), that have been extensively studied
      both in solution and in the gas phase were used as model systems in this study.
      We demonstrate that physical and chemical properties of SAM surfaces have a
      strong effect on the conformations of soft-landed peptide ions. For example,
      deposition of the alpha-helical [Ac-A(15)K + H](+) ion on the CH(3)-terminated
      (HSAM) surface results in immobilization of both the alpha- and 3(10)-helical
      conformations. In contrast, a significant fraction of Ac-A(15)K molecules are
      present in the beta-sheet conformation on the CF(3)-(FSAM) and COOH-terminated
      (COOH-SAM) surfaces. We show that the kinetic energy of the polyalanine ion, the
      charge, and the initial conformation have only a minor effect on the conformation
      of deposited species suggesting that the interaction between the molecule and the
      surface plays a major role in determining the secondary structures of immobilized
      polyalanines. This study demonstrates that SL of mass-selected ions can be
      utilized for obtaining fundamental understanding of the intrinsic properties of
      biomolecules and surfaces responsible for conformational changes upon adsorption.

PMID- 20820594
TI  - Photochemical induced growth and aggregation of metal nanoparticles in diode
      array spectrophotometer via excited dimethyl-sulfoxide.
AB  - Ag(0) and Au(0) nanoparticles suspended in dilute aqueous solutions containing
      (CH(3))(2)SO are photochemically unstable. The light source of a diode-array
      spectrophotometer induces, within less than a minute, particle growth and
      aggregation. The results indicate that this process is triggered by UV light
      absorption by the (CH(3))(2)SO.

PMID- 20820595
TI  - Hosting anions. The energetic perspective.
AB  - Hosting anions addresses the widely spread molecular recognition event of
      negatively charged species by dedicated organic compounds in condensed phases at
      equilibrium. The experimentally accessible energetic features comprise the entire
      system including the solvent, any buffers, background electrolytes or other
      components introduced for e.g. analysis. The deconvolution of all these
      interaction types and their dependence on subtle structural variation is required
      to arrive at a structure-energy correlation that may serve as a guide in receptor
      construction. The focus on direct host-guest interactions (lock-and-key
      complementarity) that have dominated the binding concepts of artificial receptors
      in the past must be widened in order to account for entropic contributions which
      constitute very significant fractions of the total free energy of interaction.
      Including entropy necessarily addresses the ambiguity and fuzziness of the host
      guest structural ensemble and requires the appreciation of the fact that most
      liquid phases possess distinct structures of their own. Apparently, it is the
      perturbation of the intrinsic solvent structure occurring upon association that
      rules ion binding in polar media where ions are soluble and abundant. Rather than
      specifying peculiar structural elements useful in anion binding this critical
      review attempts an illumination of the concepts and individual energetic
      contributions resulting in the final observation of specific anion recognition
      (95 references).

PMID- 20820596
TI  - De novo structure-based design of anion receptors.
AB  - This tutorial review presents an account of how de novo structure-based design
      methods have been used to facilitate the discovery of novel anion receptors
      formed by combination of hydrogen bond donor groups. Topics include the
      development of criteria needed for the design, how the input structures for each
      design were obtained, and subsequent use of molecular modeling to more accurately
      rank the initial list of candidates produced by the builder. The effectiveness of
      the design approach is illustrated in several cases where host molecules
      identified on the computer were subsequently synthesized and shown to function as
      efficient anion hosts.

PMID- 20820597
TI  - Cryptand-like anion receptors.
AB  - The design of supramolecular hosts for anions began with simple diaza bicycles,
      named katapinands, and has evolved over the last 40 years to a number of
      elegantly designed receptors capable of binding many different anions. About the
      same time the term cryptand appeared in reference to another bicyclic compound
      that was selective for alkaline-earth ions. Since the first report these simple
      bicycles, a vast arena of hosts has appeared, including acyclic, monocyclic, and
      other multicyclic supramolecular receptors. Studies of these systems have
      revealed considerable information about anion coordination chemistry, including
      the fact that many of these complexes mimic their transition-metal corollaries in
      terms of coordination numbers. However, for anions interactions occur via H
      bonding most often, rather than the coordinate covalent or dative bonds observed
      in transition-metal coordination. This critical review examines the design of
      enclosed, primarily bicyclic cryptands as hosts for anions, with a small
      scattering of higher polyhedra when deemed appropriate to the discussion. In
      order to show the development (evolution) of the field, key examples of early
      work will be noted and compared with more recent developments (136 references).

PMID- 20820599
TI  - Synthesis and characterization of anionic rare-earth metal amides stabilized by
      phenoxy-amido ligands and their catalytic behavior for the polymerization of
      lactide.
AB  - A dianionic phenoxyamido ligand was the first to be used to stabilize organo-rare
      earth metal amido complexes. Amine elimination reaction of Nd[N(TMS)(2)](3)(MU
      Cl)Li(THF)(3) (TMS = SiMe(3)) with aminophenol [HNOH] {[HNOH] = N-p
      methylphenyl(2-hydroxy-3,5-di-tert-butyl)benzylamine} in a 1 : 1 molar-ratio gave
      the anionic phenoxyamido neodymium amide [NO](2)Nd[N(TMS)(2)][Li(THF)](2) (2) in
      a low isolated yield. A further study revealed that the stoichiometric reactions
      of Ln[N(TMS)(2)](3)(MU-Cl)Li(THF)(3) with the lithium aminophenoxy
      [HNOLi(THF)](2) (1) in tetrahydrofuran (THF) gave the anionic rare-earth metal
      amido complexes [NO](2)Ln[N(TMS)(2)][Li(THF)](2) [Ln = Nd (2), Sm (3), Yb (4), Y
      (5)] in high isolated yields. All of these complexes are fully characterized. X
      Ray structure determination revealed that complex 1 has a solvated dimeric
      structure, and complexes 2-5 are isostructural, and have solvated monomeric
      structures. Each of the rare-earth metal ions is coordinated by two oxygen atoms
      and two nitrogen atoms from two phenoxyamido ligands and one nitrogen atom from
      the N(TMS)(2) group to form a distorted trigonal bipyramidal geometry. Each of
      the lithium atoms in complexes 2-5 is coordinated with one oxygen atom and one
      nitrogen atom from two different phenoxyamido groups, and one oxygen atom from
      one THF molecule to form a trigonal planar geometry. Furthermore, the catalytic
      behavior of complexes 2-5 for the ring-opening polymerization of l-lactide was
      explored.

PMID- 20820600
TI  - Periodic mesoporous titanium phosphonate spheres for high dispersion of CuO
      nanoparticles.
AB  - Periodic mesoporous titanium phosphonate spheres are prepared in the presence of
      surfactant Brij 56 by utilizing sodium salt of ethylene diamine tetra(methylene
      phosphonic acid) as the coupling molecule. The spherical morphology could be only
      obtained with the water-ethanol ratio of 75/25. The synthesized hybrids possess
      periodic mesoporosity with specific surface area of 606 m(2) g(-1) and irregular
      macrovoids throughout the microspheres, revealed by the measurements of X-ray
      diffraction, nitrogen adsorption, scanning and transmission electron microscopy.
      The structure and chemical states of the materials are characterized by chemical
      analysis, FT-IR, MAS NMR, XPS and thermogravimetric analysis, indicating the
      homogeneous integrity of organic groups inside the hybrid framework, which allows
      Cu(2+) ions extensively coordinated with these organic ligands. The monolayer
      adsorption behavior of Cu(2+) ions is confirmed, and further calcination of the
      Cu(2+) ion-dispersed matrix results in the highly dispersed CuO active components
      on the pore surface of mesoporous titanium phosphonates. The H(2)-TPR analysis
      and catalytic CO oxidation testing prove that the CuO nanoparticles, dispersed on
      either hybrid or inorganic supports, prepared by this coordination and
      calcination strategy, possess high oxidation activity, making them promising
      catalysts for potential environmental applications.

PMID- 20820601
TI  - Unexpected activation of carbon-bromide bond promoted by palladium nanoparticles
      in Suzuki C-C couplings.
AB  - Dihydroanthracene derivatives (1-6) containing imide (1-3) and amine (4-6)
      functions have been used for the stabilization of palladium nanoparticles,
      starting from Pd(0) and Pd(ii) organometallic precursors. Well-dispersed
      nanoparticles of mean size in the range ca. 1.9 to 3.6 nm could be obtained using
      Pd(0) precursors (PdLc and PdLd, where L = 1-6 and c and d mean the
      organometallic precursor involved, [Pd(2)(dba)(3)] and [Pd(ma)(nbd)]
      respectively). With the aim to evaluate the behaviour of homogeneous species and
      nanoparticles used as catalytic precursors, palladium complex coordinated to the
      diamine 6, [Pd(OAc)(2)(kappa(2)-N,N-6)], was prepared, reporting for the first
      time the X-ray diffraction structure of a metallic complex containing a ligand
      with a 9,10-dihydroanthracene backbone. Palladium systems were evaluated in
      Suzuki C-C coupling reactions and relevant differences were observed comparing
      the reactivity of the homogeneous systems in relation to that obtained using
      palladium nanoparticles as starting catalyst in relation to the activation of the
      C-Br bonds for deactivated substrates.

PMID- 20820602
TI  - Ag(I) and Au(I) complexes of sterically crowded cyclic phosphinimine ligands.
AB  - Cyclic phosphinimines are strong bases with structural similarities to carbene
      ligands. The cyclic phosphinimines R(2)PNCPh(2)(CH(2)CH(CO(2)Me)) (R = Ph 4, i-Pr
      5, Me 6), R(2)PNCPh(2)(CCOMe)(2) (R = Ph 7, i-Pr 8) and
      Ph(2)PNCPh(2)(CH(2)CH(CN)) 9 are readily prepared via cycloaddition of the
      compounds R(2)PNCPh(2) (R = Ph 1, i-Pr 2, Me 3) and olefins or alkynes. In the
      case of 4 this phosphinimine proved to be moisture sensitive, converting to
      Ph(2)C(NH(2))CH(CO(2)Me)CH(2)P(O)Ph(2)10 upon hydrolysis. Nonetheless, the Ag(i)
      and Au(i) complexes [{Ph(2)PNCPh(2)(CH(2)CH(CO(2)Me)}(2)Ag][NO(3)] 11
      (Ph(2)PNCPh(2)(CH(2)CH(CO(2)Me)AuCl 12 and (Ph(2)PNCPh(2)(C(CO(2)Me)(2))AuCl 13
      were prepared and characterized. Compounds 1, 2 and 7-13 have been characterized
      crystallographically.

PMID- 20820603
TI  - Synthesis, characterization, cellular uptake and interaction with native DNA of a
      bis(pyridyl)-1,2,4-oxadiazole copper(II) complex.
AB  - The copper(II) complex of 3,5-bis(2'-pyridyl)-1,2,4-oxadiazole was synthesized
      and characterized. X-Ray crystallography revealed that the complex consists of a
      discrete [Cu(3,5-bis(2'-pyridyl)-1,2,4-oxadiazole)(2)(H(2)O)(2)](2+) cation and
      two ClO(4)(-) anions. The Cu(II) coordination sphere has a distorted octahedral
      geometry and each ligand chelates the copper ion through the N(4) nitrogen of the
      oxadiazole ring and the nitrogen of one pyridine moiety. The coordinated water
      molecules are in cis position and each of them is H-bonded to the 5-pyridyl
      nitrogen of the oxadiazole ligand and to an oxygen of the perchlorate anion.
      Biological assays showed that, despite the free ligand not being effective,
      [Cu(3,5-bis(2'-pyridyl)-1,2,4-oxadiazole)(2)(H(2)O)(2)](2+) reduced the vitality
      of human hepatoblastoma HepG2 and colorectal carcinoma HT29 cells in a dose- and
      time-dependent manner. The interaction of the cationic copper complex with native
      DNA was investigated by variable-temperature UV-vis spectroscopy, circular
      dichroism, viscosity and gel electrophoresis, indicating that it is a groove
      binder with binding constant K(b) = 2.2 * 10(4) M(-1).

PMID- 20820604
TI  - Dimetallic complexes of macrocycles with two rigid dibenzofuran units as
      receptors for detection of anionic substrates.
AB  - The hexaazamacrocycles [28](DBF)(2)N(6) {cyclo[bis(4,6
      dimethyldibenzo[b,d]furaniminoethyleneiminoethylene]} and [32](DBF)(2)N(6)
      {cyclo[bis(4,6-dimethyldibenzo[b,d]furaniminopropyleneiminopropylene]} form
      stable dinuclear copper(ii) complexes suitable to behave as receptors for several
      anionic substrates. These two receptors were used to study the binding
      interactions with several substrates, such as imidazole (Him) and some
      carboxylates [benzoate (bz(-)), oxalate (ox(2-)), malonate (mal(2-)), phthalate
      (ph(2-)), isophthalate (iph(2-)), and terephthalate (tph(2-))] by
      spectrophotometric titrations and EPR spectroscopy in MeOH (or H(2)O):DMSO (1 : 1
      v/v) solution. The largest association constant was found for ox(2-) with
      Cu(2)[32](DBF)(2)N(6)(4+), whereas for the aromatic dicarboxylate anions the
      binding constants follow the trend ph(2-) > iph(2-) > tph(2-), i.e. decrease with
      the increase of the distance of the two binding sites of the substrate. On the
      other hand, the large blue shift of 68 nm observed by addition of Him to
      Cu(2)[32](DBF)(2)N(6)(4+) points out for the formation of the bridged CuimCu
      cascade complex, indicating this receptor as a potential sensor for the detection
      and determination of imidazole in solution. The X-band EPR spectra of the
      Cu(2)[28](DBF)(2)N(6)(4+) and Cu(2)[32](DBF)(2)N(6)](4+) complexes and the
      cascade complexes with the substrates, performed in H(2)O:DMSO (1 : 1 v/v) at 5
      to 15 K, showed that the CuCu distance is slightly larger than the one found in
      crystal state and that this distance increases when the substrate is accommodated
      between the two copper centres. The crystal structure of
      [Cu(2)[28](DBF)(2)N(6)(ph)(2)].CH(3)OH was determined by X-ray diffraction and
      revealed the two copper centres bridged by two ph(2-) anions at a CuCu distance
      of 5.419(1) A. Each copper centre is surrounded by three carboxylate oxygen atoms
      from two phthalate anions and three contiguous nitrogen atoms of the macrocycle
      in a pseudo octahedral coordination environment.

PMID- 20820605
TI  - Co(II), Ni(II), Cu(II) and Zn(II) complexes of a bipyridine bis-phenol conjugate:
      generation and properties of coordinated radical species.
AB  - Four bis-phenolate complexes [Zn(II)L], [Ni(II)L], [Cu(II)L] and [Co(II)L] (where
      [H(2)L = 2,2'-[2,2']bipyridinyl-6-yl-bis-4,6-di-tert-butylphenol] have been
      synthesized. The copper(II) and nickel(II) complexes have been characterized by X
      ray diffraction, showing a metal ion within a square planar geometry, slightly
      distorted towards tetrahedral. The cyclic voltametry (CV) curve of [Zn(II)L]
      consists of a single bi-electronic reversible wave at 0.06 V vs. Fc/Fc(+). The
      electrochemically generated dication is a diradical species [Zn(II)L](2+) that
      exhibits the typical phenoxyl pi-pi* band at 395 nm. It is EPR-silent due to
      magnetic interactions between the phenoxyl moieties. The CV curves of [Ni(II)L]
      and [Cu(II)L] exhibit two distinct ligand-centred one-electron oxidation waves.
      The first one is observed at E(1/2)(1) = 0.38 and 0.40 V for the nickel and
      copper complex, respectively, and corresponds to the formation of M(II)
      coordinated phenoxyl radicals. Accordingly, [Ni(II)L](+) exhibits a strong
      absorption band at 960 nm and an (S = 1/2) EPR signal centred at g(iso) = 2.02.
      [Cu(II)L](+) is EPR-silent, in agreement with a magnetic coupling between the
      metal and the radical spin. In contrast with the other complexes, [Co(II)L] was
      found to react with dioxygen (mostly in the presence of pyridine), giving rise to
      a stable (S = 1/2) superoxo radical complex [Co(III)L(Py)(O(2))]. One-electron
      oxidation of [Co(II)L] at -0.01 V affords a diamagnetic cobalt(III) complex
      [Co(III)L](+) that is inert towards O(2) binding, whereas two-electron oxidation
      leads to the paramagnetic phenoxyl radical species [Co(III)L](+) whose EPR
      spectrum features an (S = 1/2) signal at g(iso) = 2.00.

PMID- 20820606
TI  - Novel neutral hexacoordinate silicon(IV) complexes with two bidentate monoanionic
      benzamidinato ligands.
AB  - The novel neutral hexacoordinate bis(benzamidinato)silicon(iv) complexes 1-10
      (SiN(4)X(2) skeletons; X = F, Cl, Br, C, N, S, Se) were synthesised and
      characterised by elemental analyses, single-crystal X-ray diffraction (except for
      2) and NMR spectroscopy in the solid state and in solution. The dynamic behavior
      of 1 (SiN(4)Cl(2) skeleton) and 3 (SiN(4)F(2)) was additionally studied by
      variable-temperature NMR experiments. Compounds 1 and 2 (SiN(4)Br(2)) were
      obtained by reaction of SiCl(4) and SiBr(4), respectively, with two molar
      equivalents of the corresponding lithium amidinate. Compound 1 served as the
      starting material in the syntheses of 3-10, in which the two chloro ligands of 1
      were substituted by two (pseudo)halogeno or one bidentate dianionic S,S, S,Se or
      Se,Se ligand. Compound 4 contains an SiN(4)C(2) skeleton and 5-7 contain an
      SiN(6) skeleton. With the preparation of 8 (SiN(4)S(2) skeleton), 9 (SiN(4)SSe)
      and 10 (SiN(4)Se(2)) it could be demonstrated that syntheses of hexacoordinate
      silicon(iv) complexes with soft chalcogeno ligand atoms are indeed feasible.
      Compounds 9 and 10 are the first hexacoordinate silicon(iv) complexes with Si-Se
      bonds.

PMID- 20820607
TI  - Rhenium(I) and platinum(II) complexes with diimine ligands bearing acidic phenol
      substituents: hydrogen-bonding, acid-base chemistry and optical properties.
AB  - Tricarbonylchloro-rhenium(i) (1-4) and catecholato-platinum(ii) complexes (6, 7)
      of diimine ligands bearing phenol and O-protected phenol substituents have been
      prepared and fully characterised including single crystal structure analyses of
      1, 4 and 7. The redox behaviour of the catecholato platinum(ii) complexes 6 and 7
      has been probed by cyclic voltammetry, preparative oxidation and EPR spectroscopy
      (6(+), 7(+)). Reversible deprotonation of the hydroxy substituted complexes 1, 3
      and 6 to 1(-), 3(-) and 6(-) resulted in significant changes in their electronic
      spectra. The luminescence properties of the diamagnetic complexes have been
      investigated using emission spectroscopy. DFT and TD-DFT calculations were
      invoked to shed some light onto the geometric and electronic structures as well
      as the experimental spectroscopic properties of the neutral complexes 1-7, the
      radical cations 6(+) and 7(+) and the conjugate bases 1(-), 3(-) and 6(-).

PMID- 20820608
TI  - Synthesis and structures of (dialkylsilylene)bis(phosphine)-nickel, palladium,
      and platinum complexes and (eta(6)-arene)(dialkylsilylene)nickel complexes.
AB  - A series of dialkylsilylene-group 10 metal complexes (R(H)(2)Si)(Me(3)P)(2)M (M =
      Ni, Pd, Pt, R(H)(2) = 1,1,4,4-tetrakis(trimethylsilyl)butane-1,4-diyl) and novel
      (eta(6)-arene)(dialkylsilylene)nickel complexes (eta(6)-arene)(R(H)(2)Si)Ni were
      synthesized and characterized by NMR spectroscopy and X-ray analysis. The
      perpendicular geometry around the Si-M bond and the short Si-M distances of
      (R(H)(2)Si)(Me(3)P)(2)M complexes indicate the significant back donation from the
      metal to the silylene ligand.

PMID- 20820609
TI  - Synthesis and properties of 5,10,15,20-tetrakis[4-(alkoxysilyl)phenyl]porphyrins:
      an application of selective deprotection of benzaldehyde diethyl acetals in the
      presence of alkoxysilyl groups.
AB  - Selective deprotection of 4-(alkoxysilyl)benzaldehyde diethyl acetals 1a-1c in
      the two-solvent system of hydrochloric acid and chloroform gave 4
      (alkoxysilyl)benzaldehydes 2a-2c in good yields. Under these conditions,
      undesired hydrolysis of the alkoxysilyl group was minimized. The reaction of
      benzaldehydes 2a and 2b with pyrrole in the presence of boron trifluoride diethyl
      etherate led to 5,10,15,20-tetrakis[4-(alkoxysilyl)phenyl]porphyrins 3a and 3b.
      The X-ray structural analysis showed that 3b has a planar porphyrin ring and
      shows typical structural features of porphyrin rings. Hydrolysis-condensation of
      3a in the presence of a surfactant afforded a porphyrin-silica hybrid (PSH) as
      insoluble brown powder. The PSH was found to be amorphous and to consist of
      aggregated nonspherical micrometre-sized particles with rough surfaces. The PSH
      has mesopores, and the specific surface area is 330 m(2) g(-1) which increases to
      810 m(2) g(-1) upon calcination.

PMID- 20820610
TI  - Fabrication and catalytic tests of MCM-22/silicon carbide structured catalysts.
AB  - The structured catalyst of zeolite MCM-22/silicon carbide (SiC) was prepared for
      the first time through the in situ hydrothermal synthesis approach. The zeolite
      loading of the structured catalyst could be tuned by changing the synthesis time
      and applying alkali pre-treatment of SiC substrate. An additional silica layer
      formed on SiC substrate after the precalcination treatment facilitated the
      crystallization of MCM-22 zeolite on the SiC substrate. The MCM-22/SiC structured
      catalyst thus prepared exhibited good catalytic performance in the methane
      dehydroaromatization reaction.

PMID- 20820611
TI  - Synthesis and structural and magnetic characterisation of cobalt(ii) complexes of
      mixed phosphonate-antimonate ligands.
AB  - The polynucleating oxygen donor ligands, [(SbAr)(4)O(2)(PhPO(3)H)(4)(PhPO(3))(4)]
      1 and [(SbAr)(2)O(HO(3)P(t)Bu)(6)] 2, based on condensation of p
      chlorophenylstibonic acid (ArSbO(3)H(2)) and phosphonic acids, were used to
      prepare polymetallic cobalt(ii) complexes. Reaction of 1 with cobalt acetate
      under solvothermal conditions produces three different types of polymetallic
      cobalt complexes. With LiOMe/pyridine as base in MeOH a dinuclear cobalt cage,
      [Co(2)(SbAr)(4)O(4)(O(3)PPh)(4)(OMe)(4)py(2)] 3, is formed, with four Sb(ii) and
      two Co(ii) centres bridged by MU(3)-oxides and phosphonates. The pyridine in the
      structure can be replaced by 3-picoline 4, 4-picoline 5, quinoline 6, 1,2-diazole
      7, 4-phenylpyridine 8, 4-ethyl pyridine 9 and methanol 10. Using pyrazine (pyz)
      instead of pyridine under the same conditions a polymer,
      [Co(2)(SbAr)(4)O(4)(O(3)PPh)(4)(OMe)(4)(C(4)H(4)N(2))](n)11, is formed. A similar
      1D-polymer forms with 4,4'-bipyridyl-ethylene 12 in place of pyrazine. With
      Et(3)N/pyridine as base in MeCN a tetranuclear cobalt cage,
      [Co(4)(SbAr)(5)O(9)(O(3)PPh)(6)(py)(4)] 13, with five Sb(ii) centres forming a
      "bowtie" and bridging to four Co(ii) centres by phosphonates and MU(3)-oxides, is
      formed. The reaction of 2 with cobalt acetate using LiOMe/pyridine as base in
      methanol, under solvothermal conditions, produces a dinuclear Co(ii) complex,
      [Co(2)(SbAr)(2)(O(3)P(t)Bu)(3)O(2)(OMe)(2)(py)(2)] 14, with two Co(II) and two Sb
      centres at the vertices of a distorted tetrahedron. Magnetic measurements on
      selected number of these cobalt cages are reported.

PMID- 20820612
TI  - Imine-assisted C-F bond activation using low-valent cobalt compounds supported by
      trimethylphosphine ligands and formation of novel organic fluorides.
AB  - A cyclometalation reaction involving C-F bond activation at a cobalt(i) center
      with an aldazine-N atom as anchoring group affords ortho-chelated cobalt(iii)
      complexes containing a [C-Co-F] fragment [CoFMe(PMe(3))(2){(C(6)H(3)F
      ortho)CH[double bond, length as m-dash]N-R}] 5-8. Under similar reaction
      conditions pi-coordinated cobalt(0) complexes [Co(PMe(3))(3)((C(6)H(3)F
      ortho)CH[double bond, length as m-dash]N-R)] 12-14 were formed when
      [Co(PMe(3))(4)], instead of [CoMe(PMe(3))(4)], was applied. C-F bond activation
      did not occur. Carbonylation of complexes 6-8 delivered novel organic fluorides
      15-17. A proposed formation mechanism of the novel organic fluorides with
      demetallation and carbonylation of complexes 6-8 by CO is discussed with
      experimental support. As important intermediates, an acetyl cobalt complex,
      [CoFMeC[double bond, length as m-dash]O(PMe(3))(2){(C(6)H(3)F-ortho)CH[double
      bond, length as m-dash]N-R}] 20, and a 19-electron cobalt(0) complex,
      Co(CO)(3)(PMe(3))(2)21, were structurally characterized. The crystal and
      molecular structures of complexes 5, 6, 8, 12, 20 and 21 were determined by X-ray
      diffraction.

PMID- 20820613
TI  - Ferromagnetic coupling in oximato-bridged multi-decker Ni(II) clusters.
AB  - Single-, double- and triple-decker oximato-bridged Ni(ii) clusters based on
      pyridine-2-amidoxime (H(2)pyaox) have been synthesized and characterized. The
      decks have the same tetranuclear cationic units [Ni(4)(Hpyaox)(2)(pyaox)(2)](2+)
      that are stably present in the reaction solution. Magnetic studies show that
      uncommon ferromagnetic exchange between the adjacent Ni(ii) ions through the
      oxime bridges is operative in the compounds with the magnetic coupling constant
      (J) in the range 0.6-6.3 cm(-1) (H = -2JS(Ni1)S(Ni2)). Density function
      theoretical (DFT) calculations and the experimental data confirm that the N-O
      bond distances of the bridging oxime group have a decisive effect in magnetic
      coupling. For the present Ni(ii) species, the elongation of N-O bond distances
      are responsible for the switching from antiferromagnetic to ferromagnetic
      exchange with the critical bond distance of 1.394 A.

PMID- 20820614
TI  - Lacunary tungstotellurates(IV): [Te2W17O61]12-, [Te2W16O58(OH)2]14- and
      [Te2W18O62(OH)2]10-.
AB  - A simple procedure is reported for the isolation of the new lacunary
      tungstotellurate(IV) [Te(2)W(17)O(61)](12-) (1a) in multi-gram quantities, with
      (125)Te and (183)W NMR spectroscopy indicating retention of the solid state
      structure in solution. The structurally related polyanions
      [Te(2)W(16)O(58)(OH)(2)](14-) (2a) and [Te(2)W(18)O(62)(OH)(2)](10-) (2b) were
      also isolated.

PMID- 20820615
TI  - Sodium and potassium compounds of [(eta(6)-benzenecarboxylate)Cr(CO)(3)] and
      [(eta(6)-1,4-benzenedicarboxylate)Cr(CO)(3)].
AB  - Reactions of [{eta(6)-C(6)H(5)COOH}Cr(CO)(3)] with sodium and potassium hydroxide
      resulted in the corresponding alkali metal derivatives [Na(H(2)O)(3){eta(6)
      C(6)H(5)COO}Cr(CO)(3)] and [K(2)(H(2)O)(CH(3)OH)(1.5)[{eta(6)
      C(6)H(5)COO}Cr(CO)(3)](2)]. Deprotonation of [{eta(6)-p
      C(6)H(4)(COOH)(2)}Cr(CO)(3)] with sodium and potassium hydroxide gave the sodium
      compound [{Na(H(2)O)(3)}(2){eta(6)-p-C(6)H(4)(COO)(2)}Cr(CO)(3)] and the
      potassium compound [{K(2)(CH(3)OH)(H(2)O)(2)}{eta(6)-p
      C(6)H(4)(COO)(2)}Cr(CO)(3)]. All substances form two-dimensional structures in
      the solid state. Hydrogen bonds are observed in all sodium complexes between some
      carboxylate groups and coordinated water molecules. The hydrogen bonds are an
      essential part of the network. As a result of the higher coordination number of
      the potassium atoms, the polymeric networks can be constructed by direct
      interaction of the oxygen atoms of the carboxylic anions with the alkali metal
      atom. No hydrogen bonds are observed in the potassium compounds. In all
      compounds, except those of [Na(H(2)O)(3){eta(6)-C(6)H(5)COO}Cr(CO)(3)], the
      alkali metal atoms form isocarbonyl bridges to the chromium atoms.

PMID- 20820616
TI  - Engineering functionality in the multiferroic BiFeO3--controlling chemistry to
      enable advanced applications.
AB  - An in-depth look at the complex materials chemistry of multiferroics is
      undertaken. In the last decade, considerable attention has been focused on the
      search for and characterization of new multiferroic materials as scientists and
      researchers have been driven by the promise of exotic materials functionality
      (i.e., electric field control of ferromagnetism). In this manuscript we develop a
      picture of multiferroic materials, including details on the nature of order
      parameters and coupling in these materials, the scarcity of such materials,
      routes to create and control the properties in these materials, and we finish by
      investigating such effects in the model multiferroic BiFeO(3).

PMID- 20820617
TI  - Assembly of the heterometallic Au(I)-M(I) (M = Cu, Ag) clusters containing the
      dialkyne-derived diphosphines: synthesis, luminescence and theoretical studies.
AB  - The novel heterobimetallic Au(I)-M(I) (M = Cu, Ag) alkynyl-diphosphine clusters
      were effectively prepared using a family of dialkynyl-based diphosphines, PPh(2)
      C(2)-(C(6)H(4))(n)-C(2)-PPh(2) (n = 0-2). These compounds consist of
      [Au(x)M(y)(C(2)C(6)H(4)R)(2x)](y-x) clusters (x = (n + 2)(n + 3)/2; y = (n + 1)(n
      + 2)) "wrapped" in gold-diphosphine "belts" (M = Cu, n = 0, R = H (4); n = 1, R =
      H (6), OMe (8), NMe(2) (9). M = Ag, n = 0, 1, 2, R = H (5, 7, 10). The solid
      state structures of 5 and 6 have been determined by X-ray crystallographic
      studies, other complexes were characterized by NMR spectroscopy and ESI-MS
      measurements. The luminescence behavior of these compounds has been studied both
      in the solid state and solution, and intense room-temperature emission in fluid
      medium with maximum quantum yield of 0.5 (6) was detected. Computational studies
      have been carried out and the theoretical results obtained are in good agreement
      with the experimental data. The calculations provided additional information on
      the structural and electronic properties of the aggregates under investigation
      and allowed for the rationalization of the difference in their photophysical
      behavior.

PMID- 20820618
TI  - An 18+delta iridium dimer releasing metalloradicals spontaneously.
AB  - Reductive elimination of a bridged chlorine from a diiridium(iii) core,
      [(dfpbo)(2)Ir(MU-Cl)](2) (dfpbo = 2-(3.5-difluorophenyl)benzoxazolato-N,C(2)),
      afforded an iridium dimer, [(fpbo)(2)Ir](2)(MU-Cl), showing an 18+delta structure
      with a bent bridge, which can release metalloradicals spontaneously in solution
      at room temperature.

PMID- 20820619
TI  - The Pd3(dppm)3(CO)n clusters (n = 1-,2-); rare cases of anionic palladium
      species.
AB  - Two novel anionic palladium clusters, Pd(3)(dppm)(3)(CO)(n-) (Pd(3)(n); n = 1-,2
      ) were electrochemically generated from the dicationic cluster Pd(3)(2+) in 0.2 M
      THF/Bu(4)NPF(6)via two first consecutive reversible 1-electron reductions
      (Pd(3)(2+) + 1 e(-) ? Pd(3)(+), -0.210, and Pd(3)(+) + 1 e(-) ? Pd(3)(0), -0.470
      V vs. SCE) followed by two others at -2.350 (Pd(3)(0) + 1 e(-) ? Pd(3)(1-),
      reversible) and at -2.690 V vs. SCE (Pd(3)(1-) + 1 e(-) ? Pd(3)(2-),
      irreversible). The chemical stability and instability, respectively, of the
      Pd(3)(dppm)(3)(CO)(n-) clusters (Pd(3)(n); n = 1-,2-) at the time scale of the
      electrochemical experiments were addressed by DFT computations. Indeed, geometry
      optimisations (B3LYP) indicate expected Pd-Pd, Pd-P, Pd-C bond length variations,
      but severe structure distortions are noted for the anions Pd(3)(1-) and Pd(3)(2
      ), including large deviations from the planarity of the Pd(3)P(6) core and for
      the triangular frame of the Pd(3) center. Space filling models indicate that this
      skeleton distortion places the phenyl-dppm groups above the unsaturated site of
      the M(3) frame hence protecting it from any interactions with substrates, and
      hence explaining the stability of the Pd(3)(1-) species. The computed gas phase
      total energy shows a decrease going from Pd(3)(2+) to Pd(3)(1+) to Pd(3)(0) and
      to Pd(3)(1-), but increases going to Pd(3)(2-) hence corroborating the relative
      stability of these species and the observed chemical reversibility of the CV
      waves. Large steps in energy stabilisation going from Pd(3)(2+) to Pd(3)(1+) to
      Pd(3)(0) is totally consistent with the low reduction potentials associated with
      these species, but the much smaller steps going from Pd(3)(0) to Pd(3)(1-) and to
      Pd(3)(2-) corroborates their much larger reduction potentials. The host-guest
      behaviour of Pd(3)(1-) and Pd(3)(2-) in the presence of the neutral substrate
      EtO(2)C-CC-CO(2)Et (L) and CF(3)CO(2)(-) (X(-)) was examined by CV. From the
      shifts of the reduction waves, it was possible to demonstrate that Pd(3)(2+) and
      Pd(3)(+) act as host for X(-) but not Pd(3)(0), Pd(3)(1-) and Pd(3)(2-), whereas
      Pd(3)(2+), Pd(3)(+), Pd(3)(0), bind L but Pd(3)(1-) and Pd(3)(2-) do not,
      corroborating evidence for stability but non-reactivity at the same time,
      particularly for the Pd(3)(1-) cluster. All in all, these anionic clusters
      exhibit the lowest oxidation state for palladium species ever investigated.

PMID- 20820620
TI  - Synthesis of carbon-encapsulated superparamagnetic colloidal nanoparticles with
      magnetic-responsive photonic crystal property.
AB  - The core/shell structure of magnetite/carbon colloidal nanoparticles (CNPs) with
      average size about 190 nm has been prepared via a one-step solvothermal process
      using ferrocene as a single reactant. The composition, phase, and morphology of
      the nanostructure have been characterized by X-ray diffraction, and transmission
      electron microscopy. Magnetic measurements reveal the superparamagnetic nature of
      the material with a magnetization saturation of 40.2 emu/g at room temperature.
      Under the induction of an external magnetic field, strong diffraction in the
      visible light spectrum can be observed in a suspension of CNPs in ethanol and the
      diffraction wavelength varies with the strength of the external magnetic field.
      After being stored for eight months in an ethanol solution, these CNPs can still
      diffract visible lights when a magnetic field was applied, which is attributed to
      carbon coating and creating carboxyl groups on the surface of carbon shells
      introducing both a steric hindrance and electrostatic repulsions between
      magnetite nanoparticles.

PMID- 20820621
TI  - Unusual Fe9 and Fe18 structural types from the use of 2,6-pyridinedimethanol in
      Fe(III) cluster chemistry.
AB  - The syntheses, crystal structures and magnetochemical characterization are
      reported for two new Fe(III) complexes
      [Fe(18)O(6)(OH)(8)(pdm)(10)(pdmH)(4)(H(2)O)(4)](ClO(4))(10) (3) and
      [Fe(9)O(4)(OH)(2)(O(2)CMe)(10)(pdm)(pdmH)(4)](NO(3)) (4). They were synthesized
      from the use of the potentially O,N,O tridentate chelate, 2,6-pyridinedimethanol
      (pdmH(2)), in the presence or absence of carboxylate groups. Octadecanuclear
      complex 3 was obtained during reactivity studies on previously-reported
      [Fe(8)O(3)(OEt)(pdm)(4)(pdmH)(4)(EtOH)(2)](ClO(4))(5) (2), the latter undergoing
      hydrolysis to 3 on recrystallization from undried MeCN. The reaction of pdmH(2)
      with preformed [Fe(3)O(O(2)CMe)(6)(py)(3)](NO(3)) in CH(2)Cl(2) gave enneanuclear
      complex 4. Both complexes 3 and 4 are unprecedented structural types. The core of
      3 comprises a central [Fe(4)O(6)] defective-dicubane attached on either side to a
      [Fe(7)O(11)] unit, which can be described as two [Fe(4)(MU(4)-O)] tetrahedra
      fused at a common Fe atom. The core of 4 can be considered as four vertex-fused
      triangular [Fe(3)(MU(3)-O)] units. Variable-temperature (T) and -field (H) solid
      state dc and ac magnetization (M) studies were carried out on complexes 3 and 4
      in the 1.8-300 K range. Analysis of the obtained data revealed that complexes 3
      and 4 possess an S = 4 and S = 5/2 ground state spin, respectively.

PMID- 20820622
TI  - Stabilization of acyclic water tetramer in a copper(II) malonate framework
      structure.
AB  - Copper(II) complex [Cu(dpq)(mal)(H(2)O)].3H(2)O (1) (dpq = dipyrido-[3,2-d:2',3'
      f]-quinoxaline, mal = malonato) was synthesized and characterized by elemental
      analysis, infrared spectroscopy, thermogravimetric analysis and single-crystal X
      ray crystallography. The single-crystal X-ray structure of 1 reveals a square
      pyramidal structure, with the dipyrido-[3,2-d:2',3'-f]-quinoxaline and malonato
      at the equatorial positions and a water molecule at the axial position. The
      molecule acts as a building block generating a supramolecular three-dimensional
      metal-organic framework (MOF) encapsulating metal linked acyclic water tetramer.
      The H-bonding capacity of malonato and the pi-pi stacking interactions of
      dipyrido-[3,2-d:2',3'-f]-quinoxaline further reinforce the framework. The
      copper(II) bound hydroxyl group is demonstrated to mediate hydrolytic cleavage of
      plasmid pBR322 DNA under dark conditions.

PMID- 20820623
TI  - Long-range ferromagnetic ordering in a 3D Cu(II)-tetracarboxylate framework
      assisted by an unprecedented bidentate MU2-O1,N4 hypoxanthine nucleobase.
AB  - The first hypoxanthine (hypH)-assisted 3D Cu(II)-tetracarboxylate framework,
      {[Cu(2)(hypH)(0.5)(H(2)O)(0.5)(btec)].1.5H(2)O}(n) (btec = 1,2,4,5
      benzenetetracarboxylate), was synthesized and exhibits long-range ferromagnetic
      ordering below 4.5 K, which opens a new window for the applications of nucleobase
      based MOFs as magnetic materials.

PMID- 20820624
TI  - A new stable monomeric lead(ii) dithiolate Pb(SCH(2)CH(2)NMe(2))(2): an interplay
      between a dynamic "flip-flop" process in solution and conformational isomerism in
      the solid-state.
AB  - The structure and dynamic behaviour of monomeric lead(ii) dithiolate
      Pb(SCH(2)CH(2)NMe(2))(2) are studied by multi-nuclear NMR, IR and Raman
      spectroscopy in solution, as well as variable-temperature Raman spectroscopy and
      X-ray diffraction analysis in the solid-state, revealing an unusual dynamic "flip
      flop" process in solution and reversible conformational isomerism of the chelated
      five-membered rings in the solid-state.

PMID- 20820625
TI  - What contribution do detergent fatty alcohols make to sewage discharges and the
      marine environment?
AB  - To investigate the potential sources of fatty alcohols arriving at a WWTP and
      entering the receiving waters, a study was conducted at Treborth North Wales
      using compound specific stable isotope mass spectrometry (13C and 2H). Samples
      were collected from soils, marine sediments, detergents used in the catchment and
      in the WWTP. Total fatty alcohol concentrations decreased in the liquid phases
      through the treatment works with the majority of the compounds accumulating in
      the sludge (biosolids). Natural plant based detergents have delta13C values
      between -26 and -320/00 while petroleum-based detergents occupy a range between 
      25 and -300/00. The corresponding delta2H values are -2500/00 for natural sourced
      materials and -500/00 for oil-based detergents which enable these two sources to
      be separated. The influent to the WWTP contained fatty alcohols which originated
      mainly from faecal sources and natural surfactants (~75%) with a smaller amount
      potentially derived from petroleum-based surfactants (~25%). The effluents from
      the WWTP contained mainly short chain compounds with a chain length less than
      C16. Their delta2H stable isotope signature was different to the other potential
      sources examined and suggests bacterial synthesis during the treatment processes.
      The sludge had relatively high concentrations of fatty alcohols as would be
      expected from their low water solubility. The stable isotopic signatures were
      consistent with a mixture of faecal and detergent sources. The sludge in this
      area is routinely spread on agricultural land as a fertiliser and may find its
      way back into the sea via land runoff. On the basis of the mean discharge rates
      and the mean C12 concentration in the effluent, this WWTP would contribute ~300 g
      day-1 to the receiving waters. The marine sediment samples had short chain fatty
      alcohols that are typical of marine production and with stable isotope values
      that indicate exclusive marine production for the C14 potentially mixed with
      terrestrial sources for the C16 and C18 compounds. Therefore, the fatty alcohols
      in the marine sediments are not the same as those that were discharged in the
      liquid effluent and these fatty alcohols were not the ones that entered the works
      through the influent but were synthesised or recycled within the works.

PMID- 20820626
TI  - Simultaneous quantitation of parabens, triclosan, and methyl triclosan in indoor
      house dust using solid phase extraction and gas chromatography-mass spectrometry.
AB  - An integrated analytical method for the simultaneous determination of five
      parabens (methyl-, ethyl-, propyl-, butyl-, and benzyl-), triclosan, and methyl
      triclosan in indoor house dust was developed based on gas chromatographic-mass
      spectrometric technique (GC/MS). Analytes were extracted from dust samples by
      sonication. After sample cleanup by solid-phase extraction (SPE), the extracts
      were derivatized with N-methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA) and
      then analyzed by gas chromatography coupled with ion trap mass spectrometry
      operated in multiple reaction monitoring (MRM) mode. For quantitation, isotope
      labelled internal standards were used for each corresponding target analyte. Only
      0.05 g of dust sample was needed for the analysis. Method detection limits ranged
      from 6.5 to 10 ng/g, and absolute recoveries from 74% to 92%. The developed
      method demonstrated good repeatability and reproducibility, with relative
      standard deviations (RSDs) less than 16% for all the analytes. The analytes were
      determined in dust samples collected using two vacuum sampling methods from 63
      Canadian homes: a sample of fresh or "active" dust (FD) collected using a Pullman
      Holt vacuum sampler, and a composite sample taken from the household vacuum
      cleaner (HD). Methyl paraben, propyl paraben, and triclosan were detected in all
      HD and FD samples. HD samples yielded median values for methyl paraben, propyl
      paraben, and triclosan of 1080, 463, and 378 ng/g, respectively, which were
      comparable to the FD sample medians of 1120, 618 and 571 ng/g. Ethyl paraben was
      detected at frequencies of 89% in FD and 73% in HD samples, with median values of
      52 and 25 ng/g, respectively. Butyl paraben was detected at frequencies of 44% in
      FD and 75% in HD samples, with median values of <10 and 59 ng/g, respectively.
      Benzyl paraben and methyl triclosan were not detected in any of the samples
      collected by either method. Samples collected according to the fresh dust
      protocol agreed with the household vacuum samples 90% of the time. Widely
      scattered concentration levels were observed for target analytes from this
      preliminary set of 63 Canadian samples, which suggests a wide variability in
      Canadian household exposures to these chemicals.

PMID- 20820627
TI  - Manganese inhibits poly(ADP-ribosyl)ation in human cells: a possible mechanism
      behind manganese-induced toxicity?
AB  - For humans manganese is both an essential trace element and, at higher doses, a
      toxic metal. Due to the ubiquitous occurrence of manganese in foodstuff, in
      industrial countries daily dietary uptake is higher as compared to the estimated
      daily requirement. Therefore manganese deficiency is extremely rare. In contrast
      chronic manganese toxicity, affecting primarily the central nervous system, is
      more prevalent. Thus manganese occupational and dietary overexposure has been
      shown to cause progressive, permanent, neurodegenerative damage, resulting in
      syndromes similar to idiopathic Parkinson's disease. To date modes of manganese
      neurotoxic action are poorly understood and in most studies oxidative stress is
      postulated as the underlying mechanism. The present study searched on the
      cellular level for a molecular mechanism behind manganese-induced neurotoxicity
      and investigated bioavailability, cytotoxicity and genotoxicity of MnCl(2), as
      well as its impact on the DNA damage response in human cells (HeLa S3) in
      culture. Whereas up to 10 uM MnCl(2) showed no induction of DNA strand breaks
      after 24 h incubation, manganese strongly inhibited H(2)O(2)-stimulated poly(ADP
      ribosyl)ation at low, completely non-cytotoxic, for certain human exposure,
      relevant concentrations starting at 1 uM. Thereby inhibition of this essential
      DNA damage response signalling reaction was not due to a reduced gene expression
      or protein level of the responsible polymerase PARP-1. Taken together, the
      results indicate that manganese, under conditions of either overload due to high
      exposure or disturbed homeostasis, can disturb the cellular response to DNA
      strand breaks, which has been shown before (S. Katyal and P. J. McKinnon, Mech.
      Ageing Dev., 2008, 129, 483-491) to result in neurological diseases.

PMID- 20820628
TI  - Imposex in Bolinus brandaris from the Ria formosa lagoon (southern Portugal):
      usefulness of "single-site baselines" for environmental monitoring.
AB  - The present study aimed at creating a so called "single-site baseline" (SSB) of
      imposex in the purple dye murex (Bolinus brandaris) from the Ria Formosa lagoon
      (Algarve coast, southern Portugal), at the moment that the IMO Antifouling System
      Convention (banning globally the use of organotin compounds in antifouling paints
      on ships' hulls) entered into force (September 2008). In the context of
      monitoring long-term temporal trends of pollution levels, SSBs are proposed
      whenever it is difficult to obtain adequate numbers of bioindicator specimens in
      most of the study area or if significant short-term variability in imposex levels
      is likely to occur. In order to deal with these constraints, this study created a
      SSB by sampling on a monthly-basis (from October 2008 to September 2009) in a
      single site considered to be representative of the Ria Formosa as a whole
      (vicinities of the Culatra Island) and where B. brandaris is abundant all year
      round. The SSB provided a good characterisation of the monthly variation in the
      imposex indices, which ranged throughout the year between 72.7 < I% < 100; 0.08 <
      FPLI < 1.73; 1.20 < RPLI < 23.27; 1.29 < VDSI < 3.54. Only a SSB could have
      detected this large variability, which otherwise might have been unnoticed and
      would have produced biased temporal and spatial comparisons, leading to erroneous
      interpretations of environmental monitoring data. Therefore, this SSB of imposex
      in B. brandaris constitutes valuable reference data to assess the future trend of
      organotin pollution in the Ria Formosa, after the benchmark date of the complete
      eradication of organotin from antifouling agents was implemented worldwide.

PMID- 20820629
TI  - Control of crystal polymorph in microfluidics using molluscan 28 kDa Ca2(+)
      binding protein.
AB  - Biominerals produced by biological systems in physiologically relevant
      environments possess extraordinary properties that are often difficult to
      replicate under laboratory conditions. Understanding the mechanism that underlies
      the process of biomineralisation can lead to novel strategies in the development
      of advanced materials. Using microfluidics, we have demonstrated for the first
      time, that an extrapallial (EP) 28 kDa protein, located in the extrapallial
      compartment between mantle and shell of Mytilus edulis, can influence, at both
      micro- and nanoscopic levels, the morphology, structure and polymorph that is
      laid down in the shell ultrastructure. Crucially, this influence is predominantly
      dependent on the existence of an EP protein concentration gradient and its
      consecutive interaction with Ca2(+) ions. Novel lemon-shaped hollow vaterite
      structures with a clearly defined nanogranular assembly occur only where
      particular EP protein and Ca2(+) gradients co-exist. Computational fluid dynamics
      enabled the progress of the reaction to be mapped and the influence of
      concentration gradients across the device to be calculated. Importantly, these
      findings could not have been observed using conventional bulk mixing methods. Our
      findings not only provide direct experimental evidence of the potential influence
      of EP proteins in crystal formation, but also offer a new biomimetic strategy to
      develop functional biomaterials for applications such as encapsulation and drug
      delivery.

PMID- 20820631
TI  - Multiplexed protein detection using antibody-conjugated microbead arrays in a
      microfabricated electrophoretic device.
AB  - We report the development of a microfabricated electrophoretic device for
      assembling high-density arrays of antibody-conjugated microbeads for chip-based
      protein detection. The device consists of a flow cell formed between a gold
      coated silicon chip with an array of microwells etched in a silicon dioxide film
      and a glass coverslip with a series of thin gold counter electrode lines. We have
      demonstrated that 0.4 and 1 MUm beads conjugated with antibodies can be rapidly
      assembled into the microwells by applying a pulsed electric field across the
      chamber. By assembling step-wise a mixture of fluorescently labeled antibody
      conjugated microbeads, we incorporated both spatial and fluorescence encoding
      strategies to demonstrate significant multiplexing capabilities. We have shown
      that these antibody-conjugated microbead arrays can be used to perform on-chip
      sandwich immunoassays to detect test antigens at concentrations as low as 40 pM
      (6 ng/mL). A finite element model was also developed to examine the electric
      field distribution within the device for different counter electrode
      configurations over a range of line pitches and chamber heights. This device will
      be useful for assembling high-density, encoded antibody arrays for multiplexed
      detection of proteins and other types of protein-conjugated microbeads for
      applications such as the analysis of protein-protein interactions.

PMID- 20820630
TI  - Multiplexed, high-throughput analysis of 3D microtissue suspensions.
AB  - Three-dimensional (3D) tissue models have significantly improved our
      understanding of structure/function relationships and promise to lead to new
      advances in regenerative medicine. However, despite the expanding diversity of 3D
      tissue fabrication methods, approaches for functional assessment have been
      relatively limited. Here, we describe the fabrication of microtissue (MU-tissue)
      suspensions and their quantitative evaluation with techniques capable of
      analyzing large sample numbers and performing multiplexed parallel analysis. We
      applied this platform to 3D MU-tissues representing multiple stages of liver
      development and disease including: embryonic stem cells, bipotential hepatic
      progenitors, mature hepatocytes, and hepatoma cells photoencapsulated in
      polyethylene glycol hydrogels. Multiparametric MU-tissue cytometry enabled
      quantitation of fluorescent reporter expression within populations of intact MU
      tissues (n>= 102-103) and sorting-based enrichment of subsets for subsequent
      studies. Further, 3D MU-tissues could be implanted in vivo, respond to systemic
      stimuli, retrieved and quantitatively assessed. In order to facilitate
      multiplexed 'pooled' experimentation, fluorescent labeling strategies were
      developed and utilized to investigate the impact of MU-tissue composition and
      exposure to soluble factors. In particular, examination of drug/gene interactions
      on collections of 3D hepatoma MU-tissues indicated synergistic influence of
      doxorubicin and siRNA knockdown of the anti-apoptotic gene BCL-XL. Collectively,
      these studies highlight the broad utility of MU-tissue suspensions as an enabling
      approach for high n, populational analysis of 3D tissue biology in vitro and in
      vivo.

PMID- 20820632
TI  - Surface-modified microprojection arrays for intradermal biomarker capture, with
      low non-specific protein binding.
AB  - Minimally invasive biosensors are of great interest for rapid detection of
      disease biomarkers for diagnostic screening at the point-of-care. Here we
      introduce a device which extracts disease-specific biomarkers directly from the
      upper dermis, without the needle and syringe or resource-intensive blood
      processing. Using antigen-specific antibodies raised in mice as a model system,
      we confirm the analytical specificity and sensitivity of the antibody capture and
      extraction in comparison to the conventional methods based on needle/syringe
      blood draw followed by processing and antigen-specific ELISAs.

PMID- 20820635
TI  - Protein trans-splicing and its use in structural biology: opportunities and
      limitations.
AB  - Obtaining insights into the molecular structure and dynamics of a protein by NMR
      spectroscopy and other in-solution biophysical methods relies heavily on the
      incorporation of isotopic labels or other chemical modifications such as
      fluorescent groups into the protein of interest. These types of modifications can
      be elegantly achieved with the use of split inteins in a site- and/or region
      specific manner. Split inteins are split derivatives of the protein splicing
      element intein, and catalyze the formation of a peptide bond between two
      proteins. Recent progress in split intein engineering provided the opportunity to
      also perform peptide bond formation between a protein and a chemically
      synthesized peptide. We review the current state-of-the-art in preparing
      segmental isotope-labeled proteins for NMR spectroscopy, and highlight the
      importance of split intein orthogonality for the ligation of a protein from
      multiple fragments. Furthermore, we use split intein-mediated site-specific
      fluorescent labeling as a framework to illustrate the general usefulness of split
      inteins for custom protein modifications in the realm of structural biology. We
      also address some limitations of split intein technology, and offer constructive
      advice to overcome these shortcomings.

PMID- 20820633
TI  - Quantitative analysis of protein translocations by microfluidic total internal
      reflection fluorescence flow cytometry.
AB  - Protein translocation, or the change in a protein's location between different
      subcellular compartments, is a critical process by which intracellular proteins
      carry out their cellular functions. Aberrant translocation events contribute to
      various diseases ranging from metabolic disorders to cancer. In this study, we
      demonstrate the use of a newly developed single-cell tool, microfluidic total
      internal reflection fluorescence flow cytometry (TIRF-FC), for detecting both
      cytosol to plasma membrane and cytosol to nucleus translocations using the
      tyrosine kinase Syk and the transcription factor NF-kappaB as models. This
      technique detects fluorescent molecules at the plasma membrane and in the
      membrane-proximal cytosol in single cells. We were able to record quantitatively
      changes in the fluorescence density in the evanescent field associated with these
      translocation processes for large cell populations with single cell resolution.
      We envision that TIRF-FC will provide a new approach to explore the molecular
      biology and clinical relevance of protein translocations.

PMID- 20820636
TI  - A proteomic study of microgravity cardiac effects: feature maps of label-free LC
      MALDI data for differential expression analysis.
AB  - We present a computational analysis of Mass Spectrometry (MS) data based on a
      proteomic study of mice cardiac tissue samples whose measured changes in peptide
      and protein abundance were obtained under normal (control or CTRL) and simulated
      microgravity conditions (hind-limb unloading or HLU). A pipeline consisting of
      experimental and computational steps has been designed to achieve, respectively,
      pre-fractionation to simplify mouse heart protein extracts and data synthesis by
      feature consensus maps. Both acid and neutral protein fractions obtained from
      differential solubility have been digested, and peptide mixtures have been
      resolved by LC-MALDI. The computational tools employed to analyze the MS data and
      reduce their complex dimensionality have included spectra alignment, denoising
      and normalization to obtain good-quality peak detection performance. In turn,
      features could be identified and further refined by searching patterns across
      repeated measurements obtained under differential conditions (HLU-CTRL, acid
      neutral protein extracts). The assessment of reproducibility aspects for
      evaluating the efficacy of label-free comparative proteomic analysis, combined
      with the goal of identifying from HLU-CTRL consensus maps candidate proteins with
      differential expression, led to a computationally efficient approach delivering
      proteins related to the basic heart functions, cardiac stress and energy supply.

PMID- 20820637
TI  - 3D structures of membrane-associated small molecules as determined in isotropic
      bicelles.

PMID- 20820638
TI  - Development of adsorptive (non-ionic) macroporous resins and their uses in the
      purification of pharmacologically-active natural products from plant sources.

PMID- 20820640
TI  - Intermediate-dominated controllable biomimetic synthesis of gold nanoparticles in
      a quasi-biological system.
AB  - A new biomimetic strategy of creating a quasi-biological system (an aqueous
      solution containing electrolytes, peptide, enzyme and coenzyme) for the
      preparation of gold nanoparticles with uniform and tunable sizes has been put
      forward and validated, adopting environmentally-friendly reducing agents and a
      biocompatible capping ligand in aqueous solution at room temperature. The
      biomimetic synthetic route has the characteristics for good stability of the
      resulting AuNPs capped with glutathione via strong Au-S bond in aqueous solution,
      an appropriate composition of the intermediate with a redox potential favorable
      for the biomimetic reduction under mild conditions, suitable pH values to adjust
      the rate of the reduction, and the addition of enzyme catalyzing the reduction.
      By only adjusting the concentration of the reducing agent NADPH, a series of
      AuNPs with narrow size-distribution could be controllably synthesized. This
      method of rational utilization of biological processes could provide a new way
      for the sustainable development of nanotechnology.

PMID- 20820641
TI  - Formation of periodic nanoring arrays on self-assembled PS-b-PMMA film under
      rapid solvent-annealing.
AB  - Periodic nanoring arrays are prepared by self-assembled poly styrene-block
      polymethylmethacrylate (PS-b-PMMA) diblock copolymer under rapid solvent
      annealing. The dimension of the nanorings can be modified by controlling the
      solvent-annealing time.

PMID- 20820642
TI  - Analytical ultracentrifugation of colloids.
AB  - In this contribution the use of Analytical Ultracentrifugation (AUC) for the
      modern analysis of colloids is reviewed. Since AUC is a fractionation technique,
      distributions of the sedimentation coefficient, particle size and shape, molar
      mass and density can be obtained for particle sizes spanning the entire colloidal
      range. The Angstrom resolution and the reliable statistics with which particle
      size distributions can be obtained from analytical ultracentrifugation makes this
      a high resolution analysis technique for the characterization of nanoparticles in
      solution or suspension. Several examples showing successful applications of AUC
      to complex problems in colloid science are given to illustrate the broad range
      and versatility of questions that can be answered by AUC experiments.

PMID- 20820643
TI  - Dominance of broken bonds and nonbonding electrons at the nanoscale.
AB  - Although they exist ubiquitously in human bodies and our surroundings, the impact
      of nonbonding lone electrons and lone electron pairs has long been
      underestimated. Recent progress demonstrates that: (i) in addition to the shorter
      and stronger bonds between under-coordinated atoms that initiate the size trends
      of the otherwise constant bulk properties when a substance turns into the
      nanoscale, the presence of lone electrons near to broken bonds generates
      fascinating phenomena that bulk materials do not demonstrate; (ii) the lone
      electron pairs and the lone pair-induced dipoles associated with C, N, O, and F
      tetrahedral coordination bonding form functional groups in biological, organic,
      and inorganic specimens. By taking examples of surface vacancy, atomic chain end
      and terrace edge states, catalytic enhancement, conducting-insulating transitions
      of metal clusters, defect magnetism, Coulomb repulsion at nanoscale contacts,
      Cu(3)C(2)H(2) and Cu(3)O(2) surface dipole formation, lone pair neutralized
      interface stress, etc, this article will focus on the development and
      applications of theory regarding the energetics and dynamics of nonbonding
      electrons, aiming to raise the awareness of their revolutionary impact to the
      society. Discussion will also extend to the prospective impacts of nonbonding
      electrons on mysteries such as catalytic enhancement and catalysts design, the
      density anomalies of ice and negative thermal expansion, high critical
      temperature superconductivity induced by B, C, N, O, and F, the molecular
      structures and functionalities of CF(4) in anti-coagulation of synthetic blood,
      NO signaling, and enzyme telomeres, etc. Meanwhile, an emphasis is placed on the
      necessity and effectiveness of understanding the properties of substances from
      the perspective of bond and nonbond formation, dissociation, relaxation and
      vibration, and the associated energetics and dynamics of charge repopulation,
      polarization, densification, and localization. Finding and grasping the factors
      controlling the nonbonding states and making them of use in functional materials
      design and identifying their limitations will form, in the near future, a subject
      area of "nonbonding electronics and energetics", which could be even more
      challenging, fascinating, promising, and rewarding than dealing with core or
      valence electrons alone.

PMID- 20820644
TI  - Signal transmission, conversion and multiplication by polar molecules confined in
      nanochannels.
AB  - The mechanism of signal transmission, conversion and multiplication at molecular
      level has been of great interest lately, due to its wide applications in
      nanoscience and nanotechnology. The interferences between authentic signals and
      thermal noises at the nanoscale make it difficult for molecular signal
      transduction. Here we review some of our recent progress on the signal
      transduction mediated by water and other polar molecules confined in
      nanochannels, such as Y-shaped carbon nanotubes. We also explore possible future
      directions in this emerging field. These studies on molecular signal conduction
      might have significance in future designs and applications of nanoscale
      electronic devices, and might also provide useful insights for a better
      understanding of signal conduction in both physical and biological systems.

PMID- 20820645
TI  - Visible-light-driven reversible and switchable hydrophobic to hydrophilic
      nitrogen-doped titania surfaces: correlation with photocatalysis.
AB  - Visible-light-responsive nitrogen-doped titanium dioxide nanorods have been
      synthesized by a hydrothermal method at low temperature. X-Ray diffraction,
      scanning electron microscopy, UV-vis spectroscopy, and contact angle measurements
      were used to obtain the crystal structures, morphologies, visible-light
      absorbance, and hydrophobicity, respectively, of the prepared nanorods. The
      surface wettability of the samples could be reversibly tuned from hydrophobic to
      hydrophilic upon visible-light illumination. This switchable surface wettability
      is crucial since the photocatalytic activity of this nanoscaled catalyst for the
      decomposition of organic molecules exhibits a strong dependence on the surface
      wettability.

PMID- 20820647
TI  - Aqueous-based route toward noble metal nanocrystals: morphology-controlled
      synthesis and their applications.
AB  - Noble metal nanocrystals with controlled morphologies play important role in many
      fields, such as catalysis and SERS, etc. To date, solution-based methods
      developed to synthesize nanocrystals mainly exploit organic reagents as solvents
      including polyol, oleic acid/oleylamine, toluene, diphenyl ether and so on. In
      organic solvent systems, expensive organometallic precursors and toxic organic
      solvents are often used, bringing about substantial environmental issues. In this
      article, based on our recent endeavors, we will summarize facile, general aqueous
      methods to synthesize monodisperse, uniform, single and binary noble metal
      nanostructures and their applications in liquid fuel cells. We believe this
      review article will be useful to those devoted to the catalysis and nanocrystal
      fields.

PMID- 20820646
TI  - Sr(0.4)H(1.2)Nb(2)O(6).H(2)O nanopolyhedra: an efficient photocatalyst.
AB  - A photocatalyst Sr(0.4)H(1.2)Nb(2)O(6).H(2)O (HSN) nanopolyhedra with high
      surface area has been successfully prepared by a simple hydrothermal method. The
      as-prepared samples were characterized by XRD, BET, SEM, TEM and XPS. The
      electronic structure of HSN determined by DFT calculations and electrochemical
      measurement revealed that HSN is an indirect-bandgap and n-type semiconductor,
      respectively. HSN samples showed high photocatalytic activities for both pure
      water splitting and the decomposition of benzene. The rate of H(2) evolution over
      HSN was 15 times higher than that of P25 and the conversion ratio of benzene
      exceeded twice that of P25. The photocatalytic activities for water splitting can
      be greatly improved by loading various co-catalysts on HSN, such as Au, Pt, and
      Pd. The photocatalytic mechanisms were proposed based on the band structure and
      characterization results of the photocatalyst.

PMID- 20820648
TI  - Morphological and phase stability of zinc blende, amorphous and mixed core-shell
      ZnS nanoparticles.
AB  - Zinc sulfide (ZnS) nanoparticles are of interest for their luminescent and
      catalytic properties which are being considered for the next generation of
      optical, electronic and photovoltaic devices. However, ZnS nanoparticles undergo
      reversible and irreversible phase transformations under ambient conditions, so a
      detailed understanding of the nanomorphology is critical in ensuring these
      desirable properties can be controlled and maintained. Anticipating the structure
      and transformations in ZnS nanoparticles experimentally is difficult, since
      selectivity among competing phases, shapes and sizes is intrinsically linked.
      Presented here are the results of first principle computer simulations and
      advanced theoretical modelling used to investigate the relationship between size
      and shape in determining the crystallinity of ZnS nanoparticles. We find that the
      equilibrium morphology is characterised by {220} facets, irrespective of the size
      of the particle, but that the presence of different high energy facets introduced
      kinetically may significantly influence the zinc blende to amorphous ZnS
      transformation size, as well as the agglomeration behaviour. In addition to this,
      we model the relationship between transformation size, morphology and the ratio
      of crystalline core to amorphous shell and show that at small sizes, a core-shell
      crystalline/amorphous structure is thermodynamically favourable.

PMID- 20820649
TI  - Concise syntheses of selective inhibitors against alpha-1,3
      galactosyltransferase.
AB  - Several iminosugar-based uridine diphosphate galactose (UDP-Gal) mimetics 1-4
      including d- and l-epimers were designed and synthesized by concise routes, and
      these synthetic compounds were evaluated for the inhibition of alpha-1,3- and
      beta-1,4-galactosyltransferases in vitro. The experimental data demonstrated that
      l-epimer 2 displayed the strongest inhibitory activity with moderate selectivity
      against alpha-1,3-galactosyltransferase.

PMID- 20820650
TI  - Effect of substituents of alloxazine derivatives on the selectivity and affinity
      for adenine in AP-site-containing DNA duplexes.
AB  - Using the DNA duplex containing an AP site (5'-TCC AGX GCA AC-3'/3'-AGG TCN CGT
      TG-5', X = AP site, N = A, T, C, or G), we have found that 2-amino-4
      hydroxypteridine (pterin) selectively binds to guanine (G), and that the enhanced
      binding affinity for G is obtained by its methylated derivative 2-amino-6,7
      dimethyl-4-hydroxypteridine (diMe pteridine). Similarly, among the cytosine (C)
      selective ligands, i.e. derivatives of 2-amino-1,8-naphthyridine, a trimethyl
      substituted derivative (2-amino-5,6,7-trimethyl-1,8-naphthyridine) selectively
      binds to C with a strong binding affinity of 1.9 * 10(7) M(-1). In the case of
      lumazine derivatives, pteridine-2,4(1H,3H)-dione (lumazine) binds to adenine (A),
      and its methylated derivative, 6,7-dimethylpteridine-2,4(1H,3H)-dione (diMe
      lumazine) strongly binds to A with enhanced binding affinity, keeping the same
      base-selectivity. On the other hand, the benzo-annelated (with phenyl ring, 2.4
      A) derivative of lumazine, benzo[g]pteridine-2,4(1H,3H)-dione (alloxazine), can
      bind to A selectively, whereas its methylated ligand, 7,8
      dimethylbenzo[g]pteridine-2,4(1H,3H)-dione (lumichrome) selectively binds to
      thymine (T) over A, C and G. Methyl-substituted lumichrome derivatives show
      moderate binding affinities for target nucleobases. The changes in the base
      selectivity and binding affinities are discussed in detail with respect to the
      substituents of these ligands, considering hydrogen-bonding patterns, size of AP
      site and stacking interactions.

PMID- 20820651
TI  - Highly efficient macrolactonization of omega-hydroxy acids using benzotriazole
      esters: synthesis of Sansalvamide A.
AB  - A facile and mild macrolactonization reaction of omega-hydroxy acids was
      developed based on the transesterification of benzotriazole esters. Treatment of
      omega-hydroxy acids with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and
      1-hydroxy benzotriazole (HOBT) in chloroform provided macrolactones in excellent
      yields. The reactions were performed under basic, neutral and acidic conditions
      using N,N-dimethylaminopyridine (DMAP), tetrabutylammonium tetrafluoroborate
      (TBABF(4)) and BF(3).Et(2)O, respectively. A calcined hydrotalcite was also used
      instead of DMAP. Finally, to test the scope of the protocol in the synthesis of
      biologically relevant macrolactones, the total synthesis of Sansalvamide A was
      carried out.

PMID- 20820652
TI  - Pyrimidine based highly sensitive fluorescent receptor for Al3+ showing dual
      signalling mechanism.
AB  - A new fluorescent probe (5-[(4-diethylamino-2-hydroxy-benzylidene)-amino]-1H
      pyrimidine-2, 4-dione) (Receptor 1) has been synthesized by the Schiff base
      condensation of 5-aminouracil with 4-(diethylamino)salicylaldehyde. The receptor
      1 exhibits high selectively for Al(3+) in DMSO as well as in aqueous solution
      even in the presence of biologically relevant cations such as Na(+), K(+),
      Ca(2+), Mg(2+), Pb(2+) and several transition metal ions. The lowest detection
      limit for the receptor 1 was found to be 1.62 * 10(-10) M with its linear
      response towards Al(3+) in the concentration range of 1.75 * 10(-9) to 3.3 * 10(
      8) M in DMSO. Receptor 1 is the first ever example where a single molecular probe
      is able to show imine (C=N) isomerization inhibition along with twisted
      intramolecular charge transfer (TICT) in combinatorial fashion.

PMID- 20820653
TI  - A ligand-free copper (1) catalysed intramolecular N-arylation of
      diazoaminobenzenes in PEG-water: an expeditious protocol towards regiospecific 1
      aryl benzotriazoles.
AB  - An efficient and highly versatile method for the synthesis of diverse
      regiospecific 1-arylbenzotriazoles being important medicinal scaffolds, by the
      copper (1) catalysed intramolecular N-arylation of diazoaminobenzenes of 2
      haloaryldiazonium salts in PEG-water has been developed. A very simple reaction
      protocol, large number of substrate affordability and excellent yields are the
      main features of this methodology.

PMID- 20820654
TI  - Domino reactions initiated by intramolecular hydride transfers from
      tri(di)arylmethane fragments to ketenimine and carbodiimide functions.
AB  - The ability of triarylmethane and diarylmethane fragments to behave as hydride
      donors participating in thermal [1,5]-H shift/6pi-ERC tandem processes involving
      ketenimine and carbodiimide functions is disclosed. C-Alkyl-C-phenyl ketenimines
      N-substituted by a triarylmethane substructure convert into a variety of 3,3,4,4
      tetrasubstituted-3,4-dihydroquinolines, as structurally related carbodiimides
      transform into 3,4,4-trisubstituted-3,4-dihydroquinazolines via transient ortho
      azaxylylenes. The first step of these one-pot conversions, the [1,5]-H shift, is
      considered to be a hydride migration on the basis of the known hydricity of the
      tri(di)arylmethane fragment and the electrophilicity of the central
      heterocumulenic carbon atom, whereas the final electrocyclization involves the
      formation of a sterically congested C-C or C-N bond. In the cases of C,C-diphenyl
      substituted triarylmethane-ketenimines the usual 6pi-ERC becomes prohibited by
      the presence of two phenyl rings at each end of the azatrienic system. This
      situation opens new reaction channels: (a) following the initial hydride shift,
      the tandem sequence continues with an alternative electrocyclization mode to give
      9,10-dihydroacridines, (b) the full sequence is initiated by a rare 1,5 migration
      of an electron-rich aryl group, followed by a 6pi-ERC which leads to 2-aryl-3,4
      dihydroquinolines, or (c) a different [1,5]-H shift/6pi-ERC sequence involving
      the initial migration of a hydrogen atom from a methyl group at the ortho
      position to the nitrogen atom of the ketenimine function. Diarylmethane
      ketenimines bearing a methyl group at the benzylic carbon atom experience a
      tandem double [1,5]-H shift, the first one being the usual benzylic hydride
      transfer whereas the second one involves the methyl group at the initial benzylic
      carbon atom, the reaction products being 2-aminostyrenes. Diarylmethane
      ketenimines lacking such a methyl group convert into 3,4-dihydroquinolines by the
      habitual tandem [1,5]-H shift/6pi-ERC processes.

PMID- 20820655
TI  - An expedient and facile route for the general synthesis of 3-aryl substituted
      1,2,3-triazolo[1,5-a][1,4]benzodiazepin-6-ones and 1,2,3-triazolo[1,5
      a][1,5]benzodiazocin-7-ones.
AB  - We describe herein a convenient approach for the general synthesis of novel
      tricyclic scaffolds incorporating a fusion of the 1,2,3-triazole ring with
      difficultly obtainable medium sized rings such as [1,4]benzodiazepin-5-ones and
      [1,5]benzodiazocin-6-ones through Sonogashira coupling of an aryl iodide with 2
      amino-N-methyl-N-(prop-2-ynyl)benzamide or homologue followed by in situ
      diazotisation, azidation and cycloaddition reactions. The strategy also allows
      easy accessibility of the corresponding amide-reduced analogues. The operational
      simplicity and easy substrate availability make the process cost effective and
      practical.

PMID- 20820656
TI  - pH-Sensitive, N-ethoxybenzylimidazole (NEBI) bifunctional crosslinkers enable
      triggered release of therapeutics from drug delivery carriers.
AB  - This paper presents a pH-sensitive bifunctional crosslinker that enables facile
      conjugation of small molecule therapeutics to macromolecular carriers for use in
      drug delivery systems. This N-ethoxybenzylimidazole (NEBI) bifunctional
      crosslinker was designed to exploit mildly acidic, subcellular environments to
      trigger the release of therapeutics upon internalization in cells. We demonstrate
      that an analog of doxorubicin (a representative example of an anticancer
      therapeutic) conjugated to human serum albumin (HSA, a representative example of
      a macromolecular carrier) via this NEBI crosslinker can internalize and localize
      into acidic lysosomes of ovarian cancer cells. Fluorescence imaging and cell
      viability studies demonstrate that the HSA-NEBI-doxorubicin conjugate exhibited
      improved uptake and cytotoxic activity compared to the unconjugated doxorubicin
      analog. The pH-sensitive NEBI group was also shown to be relatively stable to
      biologically-relevant metal Lewis acids and to serum proteins, supporting that
      these bifunctional crosslinkers may be useful for constructing drug delivery
      systems that will be stable in biological fluids such as blood.

PMID- 20820657
TI  - Diastereoselective syntheses of 3-aryl-5-(arylalkyl)-6-methyl-1-(1
      phenylethyl)thioxotetrahydropyrimidin-4(1H)-ones: a stereochemical perspective
      from endo and exocyclic chiral centres.
AB  - Diastereoselective syntheses of 3-aryl-(S/R)-6-methyl-1-[(S/R)-1-phenylethyl)]-2
      thioxotetrahydro pyrimidin-4(1H)-ones were achieved in good yields by the
      condensation of aryl isothiocyanates with ethyl 3-(1-phenylethylamino)butanoate
      in a one-pot reaction. Benzylation of these substrates illustrated that the
      orientations of the exocylic and endocylic groups determine the stereochemical
      outcome of the product formed.

PMID- 20820658
TI  - Radical formation of amino acid precursors in interstellar regions? Ser, Cys and
      Asp.
AB  - It is proposed that the glycine precursor NH(2)CH(2)CN may be synthesised in
      interstellar dust clouds by the radical combination reactions NH(2) + CH(2)CN ->
      NH(2)CH(2)CN (DeltaG = -302 kJ mol(-1)) and/or NH(2)CH(2) + CN -> NH(2)CH(2)CN
      (DeltaG = -414 kJ mol(-1)). All calculations at the CCSD(T)/aug-cc-pVDZ//B3LYP/6
      31+G(d) level of theory. This paper extends that concept to radical/radical
      coupling reactions to form Ser, Cys and Asp precursor nitriles. The hydrogen
      abstraction process NH(2)CH(2)CN + HO-> NH(2)CHCN + H(2)O (DeltaG = -130 kJ mol(
      1)) is suggested to precede the radical coupling reactions NH(2)CHCN + R->
      NH(2)CHRCN (R = CH(2)OH, CH(2)SH and CH(2)CN) to form nitrile precursors of the
      amino acids Ser, Cys and Asp. These three reactions are all favourable (DeltaG = 
      240, -227 and -223 kJ mol(-1)). The radical species CH(2)NH(2), CH(2)OH, CH(2)SH
      and CH(2)CN are shown to be stable for the microsecond timeframe by a combination
      of theoretical calculations and the experimental mass spectrometric
      neutralization/reionization procedure.

PMID- 20820659
TI  - Enantioselective formal [2+2] cycloaddition of ketenes with nitroso compounds
      catalyzed by N-heterocyclic carbenes.
AB  - Chiral N-heterocyclic carbenes were found to be efficient catalysts for the
      formal [2+2] cycloaddition reaction of alkyl(aryl)ketenes and nitroso compounds
      to give the corresponding 1,2-oxazetidin-3-ones in moderate to good yields with
      high enantioselectivities. Reductive ring-opening of the oxazetidinones give the
      corresponding alpha-hydroxy acid derivatives in good yields.

PMID- 20820660
TI  - Radiolytic cyclization of stem-and-loop structured oligodeoxynucleotide with
      neighboring arrangement of alpha,omega-bis-disulfides.
AB  - Upon X-ray irradiation of hypoxic aqueous solution, modified
      oligodeoxynucleotides (ODNs) bearing a pair of disulfides at both ends of the
      strand that forms a stem-and-loop structure with a neighboring arrangement of
      alpha,omega-bis-disulfides underwent efficient cyclization via an intramolecular
      exchange reaction at the disulfide moieties with a multiple turnover process.
      Mechanistic studies revealed that hydrogen atoms generated in the radiolysis of
      water are key active species initiating a chain reaction to produce cyclic ODN
      disulfides, in which addition of hydrogen atom results in dissociation of the
      original disulfide bond to generate a thiyl radical intermediate as the chain
      carrier for the succeeding disulfide exchange into cyclization. The properties
      were also assessed for the resultant cyclic ODN disulfide that has several
      favorable features for use in the transcriptional decoy strategy. The cyclic ODN
      disulfides produced by the present radiolytic method showed high thermal
      stability, resistance to nuclease, and high binding activity to a representative
      transcriptional factor of nuclear factor kappaB.

PMID- 20820661
TI  - Reaction of heterocyclic enamines with nitrile oxide and nitrilimine precursors.
AB  - Alkylidenepyrrolidines 1, 21, 24 and 26 undergo reactions with nitrile oxides and
      nitrilimines or their precursors to give a range of novel heterocyclic compounds.
      With alkylidenepyrrolidine ester 1, nitrolic acids give products in which the
      liberated nitrous acid reacts with the alkylidenepyrrolidine, followed by two
      cycloadditions to give adducts 3. In contrast, hydroximoyl chlorides give
      isoxazoles 10, presumably by cycloaddition/elimination. With hydrazonyl
      chlorides, simple acylation of the alkylidenepyrrolidine occurs to give compounds
      17. With sulfonyl alkylidenepyrrolidines 24 and 26, cycloaddition onto the imine
      tautomer is the preferred pathway, with a stereoselective reaction taking place
      in the latter case.

PMID- 20820662
TI  - Selective inhibition of ADAR2-catalyzed editing of the serotonin 2c receptor pre
      mRNA by a helix-threading peptide.
AB  - RNA editing by adenosine deamination is a form of epigenetic control of gene
      expression wherein the ADAR enzymes convert adenosine to inosine in RNA often
      changing the meaning of codons. The pre-mRNA for the 2c subtype of serotonin
      receptor (5-HT2cR) is shown here to support small molecule binding near known
      editing sites. Furthermore, a helix-threading peptide binds this site and
      inhibits the in vitro reaction of ADAR2 in an RNA-substrate selective manner.
      This is the first example of substrate-selective inhibition of editing by an RNA
      binding small molecule and sets the stage for the development of new reagents
      capable of controlling gene function through manipulation of mRNA editing.

PMID- 20820663
TI  - LNA 5'-phosphoramidites for 5'->3'-oligonucleotide synthesis.
AB  - Hereby we report an efficient synthesis of LNA thymine and LNA 5-methylcytosine
      5'-phosphoramidites, allowing incorporation of LNA thymine and LNA 5
      methylcytosine into oligonucleotides synthesized in the 5'->3' direction. Key
      steps include regioselective enzymatic benzoylation of the 5'-hydroxy group of
      unprotected LNA thymine, and subsequent 4,4'-dimethoxytritylation of the 3'
      hydroxy group of the O5'-benzoylated LNA thymine nucleoside.

PMID- 20820665
TI  - A domino synthesis of benzoquinolinamide in the presence of iodine.
AB  - The domino synthesis of benzo[f]quinolinyl and benzo[h]quinolinyl acetamides from
      diketene, amines, aromatic aldehydes and naphthalenamine was developed, and the
      catalyst iodine was found to be crucial to the reaction. The structure was
      deduced from the mass spectrum, (1)H NMR, (13)C NMR spectrum and 2D NMR performed
      on two representative products.

PMID- 20820664
TI  - Asymmetric synthesis of chiral cyclic amine from cyclic imine by bacterial whole
      cell catalyst of enantioselective imine reductase.
AB  - Streptomyces sp. GF3587 and 3546 were found to be imine-reducing strains with
      high R- and S-selectivity by screening using 2-methyl-1-pyrroline (2-MPN). Their
      whole-cell catalysts produced 91 mM R-2-methylpyrrolidine (R-2-MP) with 99.2%e.e.
      and 27.5 mM S-2-MP (92.3%e.e.) from 2-MPN at 91-92% conversion in the presence of
      glucose, respectively.

PMID- 20820667
TI  - New fluorescent trans-dihydrofluoren-3-ones from aldol-Robinson annulation
      regioselective addition involved one-pot reaction.
AB  - An unexpected discovery of new trans-4-acetyl-1,9-dimethyl-4,4a-dihydro-3H
      fluoren-3-ones from one pot reactions of benzaldehydes and acetylacetone is
      described. The synthetic mechanism and stereochemistry were discussed. These new
      derivatives exhibit good fluorescent properties in solutions.

PMID- 20820666
TI  - Design, synthesis and biological evaluation of carbohydrate-functionalized
      cyclodextrins and liposomes for hepatocyte-specific targeting.
AB  - Targeting glycan-binding receptors is an attractive strategy for cell-specific
      drug and gene delivery. The C-type lectin asialoglycoprotein receptor (ASGPR) is
      particularly suitable for liver-specific delivery due to its exclusive expression
      by parenchymal hepatocytes. In this study, we designed and developed an efficient
      synthesis of carbohydrate-functionalized beta-cyclodextrins (betaCDs) and
      liposomes for hepatocyte-specific delivery. For targeting of ASGPR, rhodamine B
      loaded betaCDs were functionalized with glycodendrimers. Liposomes were equipped
      with synthetic glycolipids containing a terminal D-GalNAc residue to mediate
      binding to ASGPR. Uptake studies in the human hepatocellular carcinoma cell line
      HepG2 demonstrated that betaCDs and liposomes displaying terminal D-Gal/D-GalNAc
      residues were preferentially endocytosed. In contrast, uptake of betaCDs and
      liposomes with terminal d-Man or D-GlcNAc residues was markedly reduced. The d
      Gal/d-GalNAc-functionalized betaCDs and liposomes presented here enable
      hepatocyte-specific targeting. Gal-functionalized betaCDs are efficient molecular
      carriers to deliver doxorubicin in vitro into hepatocytes and induce apoptosis.

PMID- 20820668
TI  - Straightforward synthesis of enantiopure (R)- and (S)-trifluoroalaninol.
AB  - Two efficient routes are reported for the synthesis of both enantiomers of
      trifluoroalaninol in enantiopure form. The first pathway involves a Strecker-type
      reaction performed from a chiral trifluoromethyloxazolidine (Fox). The second
      route, which is more direct, involves, as a key step, the reduction of chiral
      oxazolidines or imines derived from ethyl trifluoropyruvate.

PMID- 20820669
TI  - Site-specific incorporation of perylene into an N-terminally modified light
      harvesting complex II.
AB  - Employing the utility of the native chemical ligation, site-specific attachment
      of an ultrastable perylene dye to a derivative of the major light-harvesting
      complex (LHCII) was demonstrated. Biochemical analysis of the conjugate indicated
      that the structure and function of LHCII remain largely unaffected by the N
      terminal modification.

PMID- 20820670
TI  - Photophysical characterization of atorvastatin (Lipitor(r)) ortho-hydroxy
      metabolite: role of hydroxyl group on the drug photochemistry.
AB  - The influence of the phenolic hydroxyl group of ortho-hydroxy atorvastatin
      metabolite (Ato-OH) on the photochemistry of atorvastatin (Ato) has been
      evaluated by steady and time-resolved experiments. Direct excitation of Ato and
      Ato-OH led to phenanthrene-like intermediate formation, being ~30% for Ato-OH
      less efficient than that for its parent compound in methanol. Both, Ato and Ato
      OH are able to quench benzophenone (E(T)~69 kcal mol(-1)) and xanthone (E(T)~74
      kcal mol(-1)) triplet excited state with rate constants close to diffusion limit
      control which suggest energy transfer mechanism is taking place. In fact, lower
      triplet energies ~63 kcal mol(-1) and pi,pi* character, were confirmed by DFT
      calculations for both compounds. Interestingly, only Ato-OH can act as a hydrogen
      donor towards triplet benzil excited state (E(T)~ 54 kcal mol(-1)) due to the
      presence of the phenolic hydroxyl group. Nevertheless, the presence of this group
      in Ato-OH does not modify to a significant degree the compound reactivity toward
      singlet oxygen. The importance of triplet energy transfer in biological systems
      to form Ato and Ato-OH triplet excited state as well as the hydrogen donor
      capacity of Ato-OH toward triplet excited state are discussed in the present
      communication.

PMID- 20820672
TI  - Diffusion pathways of oxygen species in the phototoxic fluorescent protein
      KillerRed.
AB  - The fluorescent protein KillerRed generates reactive oxygen species through the
      CALI effect. This property paves the way for the design of genetically encoded
      photosensitizers for use in cell killing and cancer photodynamic therapy. In this
      article, we have investigated the diffusion pathways of di-oxygen and the
      superoxide radical in KillerRed, using molecular dynamics simulations. Our
      results suggest that, by comparison to the Ser-65-Thr mutant of GFP, diffusion of
      molecular oxygen (and singlet oxygen) is greatly facilitated in KillerRed, mostly
      due to the presence of a unique water-filled channel. In contrast, due to their
      negative charge, superoxide radical ions putatively produced inside the
      chromophore pocket are unable to escape the protein. These results are consistent
      with the hypothesis that superoxide generation, if it occurs, proceeds via light
      induced photoreduction of the chromophore followed by long-range electron
      transfer, a mechanism in which the long hydrogen bond network through the channel
      could play a key role. Alternatively, the facilitated diffusion of di-oxygen
      through the channel suggests that singlet di-oxygen could be the principal cause
      of specific CALI of fused proteins. The entry of di-oxygen through the channel
      probably also accounts for the high susceptibility of KillerRed to
      photobleaching.

PMID- 20820673
TI  - Ultrafast excited-state dynamics in some spirooxazines and chromenes. Evidence
      for a dual relaxation pathway.
AB  - A great variety of technological applications makes photochromism a currently
      appealing theme for basic studies. In this work, excited state dynamics of two
      spirooxazines and two naphthopyrans, that upon UV irradiation undergo thermally
      reversible conversion to coloured photomerocyanines, have been investigated by
      using pump-probe techniques (femtosecond time resolution). The breakage of the C
      O bond, involved in the photoreaction, has been found to occur within a few
      hundreds of femtoseconds producing a first transient that evolved on picosecond
      time-scale to the most stable isomer through a number of intermediates that
      depended on the solvent and the structure of the photochrome. The peculiar
      behaviour of one of the molecules studied (1,3-dihydro-3,3-dimethyl-1-isobutyl-6'
      (2,3-dihydro-1H-indol-1-yl)spiro [2H-indole-2,3'-3H-naphtho[2,1-b][1,4]oxazine])
      has been investigated in depth in various media because it revealed an unusual
      dual photochemistry pathway. This finding is traced to reactivity of pi,pi* and
      ICT excited states whose relative populations are controlled by the polarity of
      the solvent.

PMID- 20820671
TI  - Human ocular carotenoid-binding proteins.
AB  - Two dietary carotenoids, lutein and zeaxanthin, are specifically delivered to the
      human macula at the highest concentration anywhere in the body. Whenever a tissue
      exhibits highly selective uptake of a compound, it is likely that one or more
      specific binding proteins are involved in the process. Over the past decade, our
      laboratory has identified and characterized several carotenoid-binding proteins
      from human retina including a pi isoform of glutathione S-transferase (GSTP1) as
      a zeaxanthin-binding protein, a member of the steroidogenic acute regulatory
      domain (StARD) family as a lutein-binding protein, and tubulin as a less
      specific, but higher capacity site for carotenoid deposition. In this article, we
      review the purification and characterization of these carotenoid-binding
      proteins, and we relate these ocular carotenoid-binding proteins to the transport
      and uptake role of serum lipoproteins and scavenger receptor proteins in a
      proposed pathway for macular pigment carotenoid delivery to the human retina.

PMID- 20820674
TI  - Effect of titanium dioxide crystalline structure on the photocatalytic production
      of hydrogen.
AB  - The effect of the crystalline phase of TiO(2) (anatase, rutile and brookite) on
      its photocatalytic activity in hydrogen production from methanol-water vapours
      has been investigated by testing a series of both home-made and commercial TiO(2)
      photocatalysts, either bare or surface-modified by deposition of a fixed amount,
      i.e. 1 wt%, of platinum as co-catalyst. For all of the TiO(2) samples the rate of
      hydrogen production increased by one order of magnitude upon Pt deposition,
      because of the ability of Pt to enhance the separation of photoproduced electron
      hole pairs. Under irradiation in the 350-450 nm wavelength range, brookite and
      anatase showed similar photoactivities, both superior to that of rutile. By
      contrast, rutile, possessing a narrower band gap, was active also under visible
      light (lambda > 400 nm), whereas no hydrogen evolution was observed with anatase
      and brookite under such conditions. Surface area proved to be a key parameter,
      strongly influencing photoactivity. However, as the particle size became ultra
      small, the semiconductor absorption edge was blue-shifted because of size
      quantisation effects, with a consequent decrease in hydrogen production rate due
      to the smaller portion of incident photons absorbed by the photocatalyst.

PMID- 20820675
TI  - Photocatalytic activity of nano and microcrystalline TiO(2) hybrid systems
      involving phthalocyanine or porphyrin sensitizers.
AB  - Hybrid photocatalysts based on TiO(2)-anatase matrix, representing the both micro
      and nano-structures, impregnated with selected lanthanide diphthalocyanine and
      metalloporphyrin sensitizers, were compared to evaluate their activity and
      effectiveness in a water suspension catalytic system designed to degrade 4
      nitrophenol (4-NP) in a UV-stimulated reaction. Either type of the anatase
      catalyst was proved to be effective in mineralizing of 4-NP. However, kinetic
      studies confirmed that the composite's efficiency basically depends on the nature
      of the macromolecular sensitizer and to a minor extent on the dimensions
      (micro/nano) of the TiO(2) particles. The apparent higher activity observed for
      the micro-TiO(2) catalysts indicates improvement of the electron transfer between
      the sensitizer and the micro-crystalline structure of TiO(2)-anatase in contrast
      to the nano-crystalline matrix. The mechanistic aspects of the observed catalytic
      performances have been discussed.

PMID- 20820676
TI  - Colorimetric detection of achiral anions and chiral carboxylates by a chiral
      thiourea-phthalimide dyad.
AB  - The chiral chemosensor 1, based on a thiourea-activated phthalimide, is available
      by four reaction steps from 4-nitrophthalimide. 1 detects fluoride, chloride,
      acetate, and dihydrogen phosphate anions by changes in UV-vis absorption.
      Fluoride in excess induces deprotonation whereas the other anions show only
      complex formation in the ground state. (1)H-NMR studies confirm the formation of
      these H-bonded complexes and the fluoride-induced receptor deprotonation in the
      recognition process. Moderate chiral recognition was observed for sodium D/L
      lactate with K(ass)(D)/K(ass)(L) = 1.93.

PMID- 20820677
TI  - Porphycene-mediated photooxidation of benzylamines by visible light.
AB  - A variety of primary and secondary benzylic amines were oxidized efficiently to N
      benzylidenebenzylamines and imines, respectively, using 2,7,12,17
      tetrapropylporphycene (H(2)TPrPc) photocatalyst and blue light emitting diodes
      (LEDs). The photooxidation of 4-methoxybenzylamine in the presence of H(2)TPrPc
      and its tin(IV) complex Sn(TPrPc)Cl(2) was studied in detail in order to show
      that operating mechanisms can be different depending on the photosensitizer type.
      Two experiments involving solvent deuterium isotope effect and competitive
      quenching with DABCO provide evidence for the singlet oxygen mechanism as the
      major pathway in the H(2)TPrPc-catalyzed reaction and the predominance of the
      direct electron transfer from the photoexcited dye to the amine when the
      Sn(TPrPc)Cl(2) complex was used as a photocatalyst.

PMID- 20820678
TI  - Laboratory apparatus for the accurate, facile and rapid determination of visible
      light photoreaction quantum yields.
AB  - A novel setup for the direct determination of the quantum yield in photocatalytic
      and photochemical processes is reported. It combines the opto-electronic
      measurement of the absorbed amount of light with established quantitative
      chemical analysis of the products. High power visible LEDs are found to be
      convenient light sources for the illumination without the need for spectral
      filtering. The LED output can be imaged efficiently and in a controlled fashion
      into the sample. The residual transmitted light is continuously monitored by a
      dedicated and calibrated solar cell. The setup can be used under the conditions
      of a chemical synthesis laboratory. All information needed for the assembly and
      operation of the device is made available. The performance is validated by
      comparison to standard chemical actinometry and by the determination of quantum
      yields for reactions reported by others and ones investigated in our own
      laboratory.

PMID- 20820679
TI  - Light-responsive nanogated ensemble based on polymer grafted mesoporous silica
      hybrid nanoparticles.
AB  - Mesoporous silica nanoparticles grafted with light-responsive polymer on the
      outer surface were developed as novel nanogated ensembles, which allow
      encapsulation and release of drug and biological molecules under light
      irradiation.

PMID- 20820680
TI  - Chiral BINOL-derived phosphoric acids: privileged Bronsted acid organocatalysts
      for C-C bond formation reactions.
AB  - BINOL-derived phosphoric acids have emerged during the last five years as
      powerful chiral Bronsted acid catalysts in many enantioselective processes. The
      most successful transformations carried out with chiral BINOL phosphates include
      C-C bond formation reactions. The recent advances have been reviewed in this
      article with a focus being placed on hydrocyanations, aldol-type, Mannich,
      Friedel-Crafts, aza-ene-type, Diels-Alder, as well as cascade and multi-component
      reactions.

PMID- 20820685
TI  - Modification of oxysulfides with two nanoparticulate cocatalysts to achieve
      enhanced hydrogen production from water with visible light.
AB  - Modification of oxysulfides, such as Sm(2)Ti(2)S(2)O(5) and Gd(2)Ti(2)S(2)O(5),
      with nanoparticulate Rh (reduction site) and Ag(2)S (oxidation site) resulted in
      enhanced H(2) production from water containing Na(2)S and Na(2)SO(3) as electron
      donors, showing an apparent quantum yield of 8.8% at 440 nm. This was
      approximately 9 or 160 times the yield achieved using samples modified with Rh or
      Ag(2)S, respectively.

PMID- 20820687
TI  - Label-free biological and chemical sensors.
AB  - Highly sensitive, label-free biodetection methods have applications in both the
      fundamental research and healthcare diagnostics arenas. Therefore, the
      development of new transduction methods and the improvement of the existing
      methods will significantly impact these areas. A brief overview of the different
      types of biosensors and the critical parameters governing their performance will
      be given. Additionally, a more in-depth discussion of optical devices, surface
      functionalization methods to increase device specificity, and fluidic techniques
      to improve sample delivery will be reviewed.

PMID- 20820686
TI  - Hydrothermal synthesis of alpha-Fe(2)O(3)@SnO(2) core-shell nanotubes for highly
      selective enrichment of phosphopeptides for mass spectrometry analysis.
AB  - In this work, we synthesized alpha-Fe(2)O(3)@SnO(2) core-shell structure
      nanotubes by a facile two-step hydrothermal method for selective enrichment of
      phosphopeptides. The core-shell structure nanotubes were found to have outer
      diameters of 90-110 nm, thicknesses of 30 nm, and lengths of 260-280 nm. SnO(2)
      nanoparticles with an average crystallite size of around 5 nm form a layer of
      about 10 nm on both walls of the alpha-Fe(2)O(3) nanotubes. To demonstrate their
      ability for selective enrichment of phosphopeptides, we applied alpha
      Fe(2)O(3)@SnO(2) nanotubes to the isolation and enrichment of the phosphopeptides
      from standard protein digestion and real samples. The enriched peptides were
      analyzed by MALDI-MS and LC-ESI MS. Experiment results demonstrate that SnO(2)
      coated alpha-Fe(2)O(3) nanotubes show excellent potential for selective
      enrichment of phosphopeptides.

PMID- 20820688
TI  - Solution synthesis of one-dimensional ZnO nanomaterials and their applications.
AB  - Recently, one-dimensional (1D) ZnO nanomaterials (NMs) have been extensively
      studied because both their functional properties and highly controllable
      morphology make them important building blocks for understanding nanoscale
      phenomena and realizing nanoscale devices. Compared with high temperature (>450
      degrees C) vapor phase methods, solution-based synthesis methods can be conducted
      at low temperatures (25-200 degrees C) allowing for compatibility with many
      organic substrate materials and offer additional advantages such as
      straightforward processing, low cost, and ease of scale up. Although there exist
      several review articles in the literature regarding the synthesis and
      applications of 1D ZnO NMs, those focusing on solution-based synthesis methods
      are lacking. Thus, this review focuses mainly on 1D ZnO NMs synthesized by
      solution-based processing. Firstly, 1D ZnO non-patterned, nanoparticle-seeded
      synthesis and its associated solution growth kinetics are discussed. Next,
      synthesis of vertically-aligned ZnO nanorod arrays with controlled pattern and
      density on various substrates is reviewed. Finally, important applications of 1D
      ZnO NMs are highlighted including sensors, field emission devices,
      photodetectors, optical switches, and solar cells.

PMID- 20820689
TI  - Extended-nano fluidic systems for analytical and chemical technologies.
AB  - Recently, integrated chemical systems have been further downscaled to the 10(1)
      10(3) nm scale, which we call extended-nano space. The extended-nano space is a
      transient space from single molecules to bulk condensed phase, and fluidics and
      chemistry have not been explored. One of the reasons is the lack of research
      tools for the extended-nano space, because the space locates the gap between the
      conventional nanotechnology (10(0)-10(1) nm) and microtechnology (>1 microm). For
      these purposes, basic methodologies were developed such as nanofabrication,
      fluidic control, detection methods, and surface modification methods. Especially,
      fluidic control is one of the important methods. By utilizing the methodologies,
      new specific phenomena in fluidics and chemistry were reported, and the new
      phenomena are increasingly applied to unique applications. Microfluidic
      technologies are now entering new research phase combined with the nanofluidic
      technologies. In this review, we mainly focus on pressure-driven or shear-driven
      extended-nano fluidic systems and illustrate the basic nanofluidics and the
      representative applications.

PMID- 20820690
TI  - Dendrimer-based organic/inorganic hybrid nanoparticles in biomedical
      applications.
AB  - This review reports some recent advances on the synthesis, self-assembly, and
      biofunctionalization of various dendrimer-based organic/inorganic hybrid
      nanoparticles (NPs) for various biomedical applications, including but not
      limited to protein immobilization, gene delivery, and molecular diagnosis. In
      particular, targeted molecular imaging of cancer using dendrimer-based
      organic/inorganic hybrid NPs will be introduced in detail.

PMID- 20820691
TI  - Probing the electronic structure of carbon nanotubes by nanoscale spectroscopy.
AB  - Among the carbon allotropes newly discovered during the last few decades, carbon
      nanotubes (CNTs) have attracted enormous attention due to their structural and
      electronic properties with strong one dimensional character. The physical and
      chemical features of such systems are intrinsically rich and complex, and can
      only be probed by using multiple experimental and theoretical techniques. In this
      feature, we focus on the structural and electronic properties of CNTs that can be
      accessed by using transmission electron energy loss spectroscopies. The latter
      are complementary to optical and X-ray absorption techniques, yet allow to obtain
      the electronic structure with nanoscale spatial resolution. An improved
      understanding of the structure-electronic properties relationship of these unique
      1D systems would represent a fundamental advance, and holds the promise of using
      CNTs in future applications.

PMID- 20820692
TI  - Silver nanowires--unique templates for functional nanostructures.
AB  - This feature article reviews the synthesis and application of silver nanowires
      with the focus on a polyol process that is capable of producing high quality
      silver nanowires with high yield. The as-synthesized silver nanowires can be used
      as both physical templates for the synthesis of metal/dielectric core/shell
      nanowires and chemical templates for the synthesis of metal nanotubes as well as
      semiconductor nanowires. Typical examples including Ag/SiO(2) coaxial nanocables,
      single- and multiple-walled nanotubes made of Au-Ag alloy, AgCl nanowires and
      AgCl/Au core/shell nanowires are discussed in detail to illustrate the
      versatility of nanostructures derived from silver nanowire templates. Novel
      properties associated with these one-dimensional nanostructures are also briefly
      discussed to shed the light on their potential applications in electronics,
      photonics, optoelectronics, catalysis, and medicine.

PMID- 20820693
TI  - Hydrothermal transformation from Au core-sulfide shell to Au nanoparticle
      decorated sulfide hybrid nanostructures.
AB  - Core-shell Au nanorod-AgAuS nanostructures were hydrothermally prepared from Au
      nanorods and metal thiobenzoates and then transformed into Au nanoparticle
      decorated sulfide nanostructures.

PMID- 20820694
TI  - Fullerol ionic fluids.
AB  - We report for the first time an ionic fluid based on hydroxylated fullerenes
      (fullerols). The ionic fluid was synthesized by neutralizing the fully protonated
      fullerol with an amine terminated polyethylene/polypropylene oxide oligomer
      (Jeffamine). The ionic fluid was compared to a control synthesized by mixing the
      partially protonated form (sodium form) of the fullerols with the same oligomeric
      amine in the same ratio as in the ionic fluids (20 wt% fullerol). In the fullerol
      fluid the ionic bonding significantly perturbs the thermal transitions and
      melting/crystallization behavior of the amine. In contrast, both the normalized
      heat of fusion and crystallization of the amine in the control are similar to
      those of the neat amine consistent with a physical mixture of the fullerols/amine
      with minimal interactions. In addition to differences in thermal behavior, the
      fullerol ionic fluid exhibits a complex viscoelastic behavior intermediate
      between the neat Jeffamine (liquid-like) and the control (solid-like).

PMID- 20820695
TI  - Synthesis and surface activity of single-crystalline Co3O4 (111) holey
      nanosheets.
AB  - Single crystalline, thermally stable, Co(3)O(4) (111) holey nano-sheets were
      prepared by an efficient, template-free, wet chemical synthetic approach. The
      high energy (111) surfaces formed can be used as highly active heterogeneous
      catalysts for methanol decomposition.

PMID- 20820696
TI  - Large-scale fabrication of single crystalline tin nanowire arrays.
AB  - Large-scale single crystalline tin nanowire arrays with preferred lattice
      orientation along the [100] direction were fabricated in porous anodic aluminium
      oxide (AAO) membranes by the electrodeposition method using copper nanorod as a
      second electrode.

PMID- 20820697
TI  - Surface plasmon resonance of gold nanoparticles assemblies at liquid | liquid
      interfaces.
AB  - Surface plasmon resonance (SPR) was observed when a planar close-packed assembly
      of gold nanoparticles (Au NPs) is adsorbed at the water|1,2-dichloroethane
      interface. Aqueous gold nanoparticles, 13 or 16 nm in diameter, are deposited at
      the interface by adding methanol to form a close-packed film with a visible gold
      mirror reflectance. By total internal reflection of a light beam on the
      interface, the angular dependence of the interfacial reflectivity was measured in
      a pseudo-Kretschmann configuration and compared to Fresnel simulations for a
      homogeneous gold film. The experimental angles for minimum reflectivity were
      found to match the simulated values. Then, the fluorescence of dye molecules co
      adsorbed within 13 and 16 nm gold nanoparticles assemblies at the liquid|liquid
      interface was measured. The fluorescence intensity under SPR is revealed to be
      much greater than under total internal reflection conditions, yielding an
      enhancement factor of approximately 30 and 50 for 13 and 16 nm Au NPs assemblies,
      respectively. Also, the fluorescence lifetime was found to decrease under SPR
      conditions.

PMID- 20820698
TI  - Synthesis of continuous TiC nanofibers and/or nanoribbons through electrospinning
      followed by carbothermal reduction.
AB  - Continuous titanium carbide (TiC) nanofibers that possess an intriguing
      nanoribbon morphology with a width and thickness of approximately 300 nm and
      approximately 40 nm, respectively, and containing TiC crystallites with sizes
      ranging from 5 nm to 30 nm were synthesized through electrospinning followed by
      carbothermal reduction.

PMID- 20820699
TI  - Complex ZnO nanotree arrays with tunable top, stem and branch structures.
AB  - Hierarchical tree-, mushroom- and cockscomb-like ZnO arrays with increasing
      branching order and complexities have been grown in situ on cheap zinc plates by
      a simple hydrothermal oxidation approach. Their morphology, crystal structure and
      orientation relationship are characterized by powder X-ray diffraction, scanning
      electron microscopy (SEM) and cross-sectional high-resolution transmission
      electron microscopy (HRTEM). The wurtzite ZnO arrays, growing mainly in the
      [0001] direction, show a special orientation relationship between the stem and
      the branch as well as a novel stem-branch boundary which might be attributed to
      the least mismatch between [symbol: see text] and (0002) lattice planes. The co
      solvent ethylenediamine (en) was used to control the morphology and complexing of
      these complex ZnO nanostructures. Correspondingly, the physical properties of ZnO
      nanostructure assembly arrays were tuned and a stronger UV emission was observed
      with negligible emissions in the visible range, indicating the highly crystalline
      features of the complex ZnO micro-/nanostructured materials.

PMID- 20820700
TI  - Facile synthesis of iv-vi SnS nanocrystals with shape and size control:
      nanoparticles, nanoflowers and amorphous nanosheets.
AB  - SnS nanocrystals have been synthesized in a simple and facile way.
      Sn(6)O(4)(OH)(4) is introduced to synthesize tin sulfide, which is used as tin
      precursor. By changing the reaction conditions (reaction temperature and Sn/S
      molar ratio), SnS nanocrystals with different shape and size can be produced. SnS
      nanoparticles and nanoflowers with orthorhombic crystal structure have uniform
      size distribution. The SnS nanoflowers firstly transform to polycrystalline
      nanoflowers, and then become amorphous nanosheets. The drive force of
      amorphization reduces the high free-energy of nanocrystals. The layered crystal
      structure of SnS is the main reason for the shape evolution and amorphization
      processes. The optical properties of nanoparticles are investigated by optical
      absorption spectra. The optical direct band gap and optical indirect band gap in
      SnS nanoparticles are 3.6 eV and 1.6 eV, respectively. Compared to direct band
      gap (1.3 eV) and indirect band gap (1.09 eV) in bulk SnS, both direct transition
      and indirect transition in nanoparticles show an obvious quantum-size effect.

PMID- 20820701
TI  - Growth of horizontally aligned single-walled carbon nanotubes on anisotropically
      etched silicon substrate.
AB  - Directional controllability of single-walled carbon nanotubes (SWNTs) is an
      important issue for future nanoelectronics applications. For direct integration
      of carbon nanotubes with modern electronics, aligned growth of carbon nanotubes
      on SiO(2)/Si is desirable. We developed a new method to horizontally align SWNTs
      directly on SiO(2)/Si substrate by creating trenches on Si(100) through
      anisotropic etching followed by thermal oxidation. The V-shaped trenches highly
      improved the alignment of SWNTs and the degree of alignment is comparable to the
      step-templated alignment of carbon nanotubes on crystals. The trenches also
      improved the density of aligned nanotubes due to the combination of "trench
      guided" and gas-flow guided alignment. Our new insights on carbon nanotube
      alignment on SiO(2)/Si will greatly contribute to future large-scale
      nanoelectronic applications.

PMID- 20820702
TI  - Design and characterization of optical nanorulers of single nanoparticles using
      optical microscopy and spectroscopy.
AB  - Current conventional imaging methods cannot determine sizes of single
      nanoparticles (NPs) in solution and living organisms at the nanometre scale,
      which limits the applications of NPs. In this study, we developed new imaging
      calibration approaches to characterize the sizes of single Ag NPs in solution at
      nanometre resolution by measuring their size-dependent scattering localized
      surface-plasmon-resonance (LSPR) spectra and scattering intensity using dark
      field optical microscopy and spectroscopy (DFOMS). We synthesized nearly
      spherical shape Ag NPs, ranging from 2 to 110 nm in diameter, and characterized
      the sizes of single NPs using high-resolution transmission electron microscopy,
      and the LSPR spectra and scattering intensity of single NPs using DFOMS. We
      constructed calibration curves of the peak wavelength (lambda(max)) of LSPR
      spectra or scattering intensity of single NPs versus their sizes. These
      calibration curves allow us to determine the sizes of single NPs at 1 nm
      resolution by measuring the LSPR spectra or scattering intensity of single NPs
      using DFOMS. These new approaches enable us to create optical nanorulers
      (calibration curves) of single Ag NPs for simultaneously imaging and measuring
      sizes of multiple single NPs in solution in real time at nanometre resolution
      using optical microscopy. One can now use these new imaging calibration
      approaches to study and characterize single NPs in solution and living organisms
      in real time for a wide variety of applications.

PMID- 20820703
TI  - Removal of acrylic coatings from works of art by means of nanofluids:
      understanding the mechanism at the nanoscale.
AB  - Conservation of works of art often involves the inappropriate application of
      synthetic polymers. We have proposed the use of alternative methodologies for
      conservation and formulated innovative cleaning nanostructured systems to remove
      previously applied polymer films and grime from painted surfaces. In particular,
      a novel "micellar system" composed of water, SDS, 1-pentanol, ethyl acetate and
      propylene carbonate was recently formulated and successfully used to remove
      acrylic and vinyl/acrylic copolymers from Mesoamerican wall paintings in the
      archeological site of Cholula, Mexico. This contribution reports on the mechanism
      of the interaction process that takes place between the nanostructured fluid and
      the polymer coating at the nanoscale. The structural properties of the "micellar
      solution" and of the polymer film are investigated before, during and after the
      interaction process using several surface and solution techniques. Rather than a
      classical detergency mechanism, we demonstrate that micelles act as solvent
      containers and interact with the polymer film leading to its swelling and
      detachment from the surface and to its segregation in a liquid droplet, which
      phase-separates from the aqueous bulk. After the removal process the micelles
      become smaller in size and undergo a structural re-arrangement due to the
      depletion of the organic solvents. These findings can be framed in an interaction
      mechanism which describes the removal process, opening up new perspectives in the
      design and formulation of new cleaning systems specifically tailored for
      intervention on particular conservation issues.

PMID- 20820704
TI  - Numerical investigations into mechanical properties of hexagonal silicon carbon
      nanowires and nanotubes.
AB  - Single-crystalline hexagonal faceted silicon carbon nanowires and nanotubes
      possess simultaneous high strength and failure strain. As long as SiC nanowires
      or nanotubes are large or thick enough to sustain a single atomic configuration
      under loading, their mechanical properties are size independent. Surface atoms
      are firstly forced to move by stretching and then destroy the equilibrium of
      subsurface atoms. Then, the force in carbon-silicon bonds along the tensile
      directions becomes larger than that in other bonds and results in elongation by
      three-times of the former than that of the latter. However, the latter bonds
      connecting the surface to the subsurface are broken and the wires or tubes are
      ruptured. For thinner nanowires and nanotubes, the broken bonds don't propagate
      instantly, but initiate transformation from a wurtzite to a graphitic structure.
      This structure transformation can strengthen and plasticize SiC nanowires and
      nanotubes.

PMID- 20820705
TI  - Gel-carbon nanotube materials: the relationship between nanotube network
      connectivity and conductivity.
AB  - The electrical resistance of carbon nanotube networks (NNs) prepared from
      combinations of gellan gum, xanthan gum, Triton X-100, SWNT and MWNT is reported.
      It is demonstrated that the NN conductivity can be obtained by analysing the
      resistance of two overlapping NN as a function of their overlap distance.
      Unexpectedly, the connectivity between two overlapping NN was found to scale with
      the electrical conductivity over 4 orders of magnitude. Insights into the
      dependence of inter-NN contact on applied pressure were obtained.

PMID- 20820706
TI  - Fabrication of self-supporting porous silicon membranes and tuning transport
      properties by surface functionalization.
AB  - This study presents a simple approach to perform selective mass transport through
      freestanding porous silicon (pSi) membranes. pSi membranes were fabricated by the
      electrochemical etching of silicon to produce membranes with controlled structure
      and pore sizes close to molecular dimensions (approximately 12 nm in diameter).
      While these membranes are capable of size-exclusion based separations, chemically
      specific filtration remains a great challenge especially in the biomedical field.
      Herein, we investigate the transport properties of chemically functionalized pSi
      membranes. The membranes were functionalized using silanes (heptadecafluoro
      1,1,2,2-tetrahydrodecyl)dimethylchlorosilane (PFDS) and N-(triethoxysilylpropyl)
      o-polyethylene oxide urethane (PEGS) to give membranes hydrophobic (PFDS) and
      hydrophilic (PEGS) properties. The transport of probe dyes tris(2,2'
      bipyridyl)dichlororuthenium(ii) hexahydrate (Rubpy) and Rose Bengal (RB) through
      these functionalized membranes was examined to determine the effect surface
      functionalization has on the selectivity and separation ability of pSi membranes.
      This study provides the basis for further investigation into more sophisticated
      surface functionalization and coupled with the biocompatibility of pSi will lead
      to new advances in membrane based bio-separations.

PMID- 20820707
TI  - Covalent modification and exfoliation of graphene oxide using ferrocene.
AB  - Large scale preparation of single-layer graphene and graphene oxide is of great
      importance due to their potential applications. We report a simple room
      temperature method for the exfoliation of graphene oxide using covalent
      modification of graphene oxide with ferrocene to obtain single-layer graphene
      oxide sheets. The samples were characterized by FESEM, HRTEM, AFM, EDAX, FT-IR,
      Raman and Mossbauer spectroscopic studies. HRTEM micrograph of the covalently
      modified graphene oxide showed increased interlayer spacing of approximately 2.4
      nm due to ferrocene intercalation. The presence of single-layer graphene oxide
      sheets were confirmed by AFM studies. The covalently modified ferrocene-graphene
      oxide composite showed interesting magnetic behavior.

PMID- 20820708
TI  - Fundamental properties of oligo double-stranded DNA/single-walled carbon nanotube
      nanobiohybrids.
AB  - Fundamental properties of single-walled carbon nanotubes (SWNTs) that are
      individually dissolved using twenty base paired-double-stranded (ds) DNA,
      (dA)(20)/(dT)(20), as well as single-stranded (ss) twenty-mers of oligo DNAs,
      adenine (dA)(20) and thymine (dT)(20), for comparison are described. In this
      study, unbound oligo DNAs are fully removed from the hybrid aqueous solutions
      using size-exclusion chromatography (SEC)-HPLC. Each SEC chromatogram of the
      solutions shows two separated peaks; one is the free oligo DNAs and the others
      are the oligo DNA/SWNT hybrids. The earlier eluent fractions (the hybrids) are
      separated into four size-separated fractions, and then their stability is
      evaluated by the re-injection of the fractions. The chromatograms of the earlier
      eluent fractions are almost identical to those of the original ones even after
      storage for one month, indicating the high stability of the dsDNA/SWNTs and
      ssDNA/SWNTs hybrids in water. The results free us from considering the desorption
      of the bound-oligo dsDNA or oligo ssDNA from their nanohybrids with the SWNTs,
      which is of significant advantage to the utilization of oligo DNA/SWNT
      nanobiohybrids in wide areas of science. We also investigated the near-IR
      absorption and photoluminescence (PL) spectral behaviors of the fractionated
      oligo DNA/SWNTs hybrids not containing corresponding free oligo DNA.

PMID- 20820709
TI  - 2D analogues of the inverted hexagonal phase self-assembled from 4,6
      dialkoxylated isophthalic acids at solid-liquid interfaces.
AB  - Self-assembly of organic molecules at solid-liquid interfaces is a route for
      developing novel functional materials on surfaces and modeling assembly phenomena
      in 3D. 5-Alkoxylated isophthalic acids (ISA) are known to self-assemble into two
      dimensional (2D) lamellae at the interface between a surface of Au(111) or HOPG
      (highly oriented pyrolytic graphite) and a solvent. Presently, the self-assembly
      of 4,6-dialkoxylated isophthalic acid derivatives with variable alkyl chain
      length is investigated at Au(111)-water, Au(111)-tetradecane and HOPG-tetradecane
      interfaces with a particular focus on the first one. The main aspect of this
      study is to evaluate the role of the molecular geometry and different
      interactions in the 2D assembly of amphiphilic molecules. In contrast to 5
      alkoxylated ISA, 4,6-dialkoxylated ISA derivatives self-assemble preferentially
      into arrays of cyclic pentameric/hexameric structures, which appear as 2D
      analogues of the inverted hexagonal phase of lipids. As a general trend, the
      derivatives bearing shorter alkyl chains show a higher level of ordering at
      Au(111)-liquid interfaces. In particular, at the Au(111)-water interface, the 4,6
      diheptyloxy ISA derivative forms exclusively pentamers, which are arranged in a
      quasi-hexagonal lattice. Moreover, the cyclic pentameric features are not empty
      but host a single isophthalic acid residue which is found to be dynamic. Finally,
      the packing of the diheptyloxy derivative shows a distinct potential dependence:
      while at more negative potentials the pentameric arrangement is converted into
      lamellae, at more positive potentials a loosely packed zig-zag pattern is formed.
      The present results show that at different solid-liquid interfaces 4,6
      dialkoxylated ISA derivatives tend to form cyclic structures that are 2D
      analogues of an inverted hexagonal phase, akin to lipids having two hydrophobic
      alkyl chains and a small polar head group. Moreover, the substrate potential at
      the Au(111)-water interface can tune the 2D molecular arrangement.

PMID- 20820710
TI  - Structuration of pH-responsive fluorescent molecules on surfaces by soft
      lithographic techniques.
AB  - Two different soft lithographic techniques (LCW and microCP) have been
      successfully used for the structuration of fluorescent pH-responsive molecules on
      surface. The molecules of choice, fluorescein (1) and a new catechol derivative
      (2), exhibit several protonation states with distinct emission properties over a
      large acid-base range. This allowed us to fabricate fluorescent arrays that
      respond over a large pH-window.

PMID- 20820716
TI  - FoF1-ATPase, rotary motor and biosensor.
AB  - F(o)F(1)-ATPase is an amazing molecular rotary motor at the nanoscale. Single
      molecule technologies have contributed much to the understanding of the motor.
      For example, fluorescence imaging and spectroscopy revealed the physical rotation
      of isolated F(1) and F(o), or F(o)F(1) holoenzyme. Magnetic tweezers were
      employed to manipulate the ATP synthesis/hydrolysis in F(1), and proton
      translation in F(o). Here, we briefly review our recent works including a
      systematic kinetics study of the holoenzyme, the mechanochemical coupling
      mechanism, reconstituting the delta-free F(o)F(1)-ATPase, direct observation of
      F(o) rotation at single molecule level and activity regulation through external
      links on the stator.

PMID- 20820717
TI  - Nano active materials for lithium-ion batteries.
AB  - Lithium-ion batteries have been widely used to power portable electronic devices,
      such as mobile phones, digital cameras, laptops etc., and are considered to be a
      promising choice of power system for the next generation of electric vehicles,
      which are central to the reduction of CO(2) emissions arising from transport. In
      order to increase energy and power density to meet the future challenges of
      energy storage, many efforts have been made to develop nano active materials for
      lithium-ion batteries. Herein we review the advantages of nano active materials
      for lithium-ion batteries. Moreover, some disadvantages of nano active materials
      and their solutions are also discussed.

PMID- 20820718
TI  - Properties, synthesis, and growth mechanisms of carbon nanotubes with special
      focus on thermal chemical vapor deposition.
AB  - Carbon nanotubes (CNTs) have been extensively investigated in the last decade
      because their superior properties could benefit many applications. However, CNTs
      have not yet made a major leap into industry, especially for electronic devices,
      because of fabrication challenges. This review provides an overview of state-of
      the-art of CNT synthesis techniques and illustrates their major technical
      difficulties. It also charts possible in situ analyses and new reactor designs
      that might enable commercialization. After a brief description of the CNT
      properties and of the various techniques used to synthesize substrate-free CNTs,
      the bulk of this review analyzes chemical vapor deposition (CVD). This technique
      receives special attention since it allows CNTs to be grown in predefined
      locations, provides a certain degree of control of the types of CNTs grown, and
      may have the highest chance to succeed commercially. Understanding the primary
      growth mechanisms at play during CVD is critical for controlling the properties
      of the CNTs grown and remains the major hurdle to overcome. Various factors that
      influence CNT growth receive a special focus: choice of catalyst and substrate
      materials, source gases, and process parameters. This review illustrates
      important considerations for in situ characterization and new reactor designs
      that may enable researchers to better understand the physical growth mechanisms
      and to optimize the synthesis of CNTs, thus contributing to make carbon nanotubes
      a manufacturing reality.

PMID- 20820719
TI  - Flame spray pyrolysis: An enabling technology for nanoparticles design and
      fabrication.
AB  - Combustion of appropriate precursor sprays in a flame spray pyrolysis (FSP)
      process is a highly promising and versatile technique for the rapid and scalable
      synthesis of nanostuctural materials with engineered functionalities. The
      technique was initially derived from the fundamentals of the well-established
      vapour-fed flame aerosols reactors that was widely practised for the
      manufacturing of simple commodity powders such as pigmentary titania, fumed
      silica, alumina, and even optical fibers. In the last 10 years however, FSP
      knowledge and technology was developed substantially and a wide range of new and
      complex products have been synthesised, attracting major industries in a diverse
      field of applications. Key innovations in FSP reactor engineering and precursor
      chemistry have enabled flexible designs of nanostructured loosely-agglomerated
      powders and particulate films of pure or mixed oxides and even pure metals and
      alloys. Unique material morphologies such as core-shell structures and nanorods
      are possible using this essentially one step and continuous FSP process. Finally,
      research challenges are discussed and an outlook on the next generation of
      engineered combustion-made materials is given.

PMID- 20820720
TI  - Preparation and applications of functional nanofibers based on the combination of
      electrospinning, controlled radical polymerization and 'Click Chemistry'.
AB  - This feature article provides an overview of the preparation of functional
      nanofibers by combined electrospinning, controlled radical polymerization and
      'Click Chemistry'. A combination of the powerful capability of controlled radical
      polymerization and 'Click Chemistry' for the synthesis of functional
      macromolecules and on surface modification as well as their wide applicability to
      electrospinning materials, functional nanofibers with a crosslinked structure,
      core-shell structures, and switchable surface properties etc. were prepared. In
      addition, the applications of the functional nanofibers in antibacterial fields
      and controlled release are also explored.

PMID- 20820721
TI  - One-dimensional boron nanostructures: Prediction, synthesis, characterizations,
      and applications.
AB  - One-dimensional (1D) boron nanostructures are very potential for nanoscale
      electronic devices since their physical properties including electric transport
      and field emission have been found very promising as compared to other well
      developed 1D nanomaterials. In this article, we review the current progress that
      has been made on 1D boron nanostructures in terms of theoretical prediction,
      synthetic techniques, characterizations and potential applications. To date, the
      synthesis of 1D boron nanostructures has been well-developed. The popular
      structures include nanowires, nanobelts, and nanocones. Some of these 1D
      nanostructures exhibited improved electric transport properties over bulk boron
      materials as well as promising field emission properties. By current experimental
      findings, 1D boron nanostructures are promising to be one of core materials for
      future nanodevices. More efforts are expected to be made in future on the
      controlled growth of 1D boron nanostructures and tailoring their physical
      properties.

PMID- 20820722
TI  - Hybrid materials based on Pd nanoparticles on carbon nanostructures for
      environmentally benign C-C coupling chemistry.
AB  - The combination of different nanomaterials such as metallic nanoparticles and
      carbon nanostructures in a new hybrid material should give rise to interesting
      properties that combine the advantages of each of the nanocomponents. This review
      highlights the latest advances in the synthetic design of these hybrid materials
      where carbon nanostructures act as supports as well as stabilizing agents for
      very reactive metallic nanoparticles. The striking applications of Pd
      nanoparticles anchored on the surface of carbon nanostructures in C-C coupling
      chemistry are analyzed. Special emphasis is placed on the stability of these
      materials, which is linked to their recyclability. Numerous examples are given
      that involve the use of these catalysts in Heck, Suzuki and Sonogashira coupling
      reactions.

PMID- 20820723
TI  - Patterning of hydrophobic three-dimensional carbon nanotube architectures by a
      pattern transfer approach.
AB  - Hydrophobic three-dimensional carbon nanotube architectures with patterned
      morphologies have been fabricated by a pattern transfer method, in which the
      components of the masks served as promoters/inhibitors to increase/decrease the
      catalyst activity for the self-organization of carbon nanotubes into a family of
      patterned nanoarchitectures.

PMID- 20820724
TI  - Estimating conformation content of a protein using citrate-stabilized Au
      nanoparticles.
AB  - Herein we report the use of the optical properties of citrate-stabilized gold
      nanoparticles (Au NPs) for estimation of native or denatured conformation content
      in a mixture of a protein in solution. The UV-vis extinction spectrum of citrate
      stabilized Au NPs is known to broaden differently in the presence of native and
      denatured states of alpha-amylase, bovine serum albumin (BSA) or amyloglucosidase
      (AMG). On the other hand, herein we show that when a mixture of native and
      denatured protein was present in the medium, the broadening of the spectrum
      differed for different fractional content of the conformations. Also, the total
      area under the extinction spectrum varied linearly with the change in the mole
      fraction content of a state and for a constant total protein concentration.
      Transmission electron microscopy (TEM) measurements revealed different levels of
      agglomeration for different fractional contents of the native or denatured state
      of a protein. In addition, time-dependent denaturation of a protein could be
      followed using the present method. The rate constants calculated for denaturation
      indicated a possible fast change in conformation of a protein before complete
      thermal denaturation. The observations have been explained based on the changes
      in extinction coefficient (thereby oscillator strength) upon interaction of
      citrate-stabilized NPs with proteins being in different states and levels of
      agglomeration.

PMID- 20820725
TI  - Development of nanoparticle probes for multiplex SERS imaging of cell surface
      proteins.
AB  - Multiplexed SERS imaging of receptor proteins on the surface of mammalian cells
      has been carried out using functionalized silver nanoparticles. Deconvolution of
      four differently functionalized nanoparticles is readily achieved, and using this
      approach, receptor co-localization can be probed and protein-protein interactions
      can be elucidated at the surface of cells.

PMID- 20820726
TI  - Absolute quantum yield measurements of colloidal NaYF4: Er3+, Yb3+ upconverting
      nanoparticles.
AB  - In this communication we describe a technique for measuring the absolute quantum
      yields (QYs) of upconverting nanomaterials based on the use of a commercially
      available fluorimeter and an integrating sphere. Using this setup, we have
      successfully acquired luminescence efficiency data (pump laser, absorbed pump,
      and visible emitted intensities) for lanthanide-doped upconverting nanoparticles.
      QYs in the range of 0.005% to 0.3% were measured for several NaYF(4): 2% Er(3+),
      20% Yb(3+) nanoparticles with particle sizes ranging from 10 to 100 nm while a QY
      of 3% was measured for a bulk sample.

PMID- 20820727
TI  - Opening of DNA double helix at room temperature: Application of alpha
      cyclodextrin self-aggregates.
AB  - Self-aggregation of alpha-cyclodextrin (alpha-CD) can induce DNA opening at room
      temperature (25 degrees C) owing to the hydroxyl groups on the surface of the
      spherical aggregates of alpha-CD, which promote hydrogen bonding with the flipped
      out bases in DNA duplex prohibiting them from reverting back.

PMID- 20820728
TI  - Surface diffusion driven nanoshell formation by controlled sintering of
      mesoporous nanoparticle aggregates.
AB  - We report a general method for the synthesis of hollow structures of a variety of
      functional inorganics by partial sintering of mesoporous nanocrystal aggregates.
      The formation of a thin shell initiates the transport of mass from the interior
      leading to growth of the shell. The principles are general and the hollow
      structures thus produced are attractive for many applications including
      catalysis, drug delivery and biosensing.

PMID- 20820729
TI  - Nanoscale heterogeneities in CeO2-ZrO2 nanocrystals highlighted by UV-resonant
      Raman spectroscopy.
AB  - Selection of the excitation wavelength at nonresonant and resonant Raman
      conditions provided detection selectivity in the tetragonal and cubic phases in
      CeO(2)-ZrO(2) nanocrystals, respectively. It was suggested that cubic-phase
      domains containing Ce(3+) deficiencies were involved in the tetragonal-phase
      matrix.

PMID- 20820730
TI  - A density functional study of strong local magnetism creation on MoS2 nanoribbon
      by sulfur vacancy.
AB  - In this study a low-width MoS(2) ribbon has been used for probing the electronic
      structure and local magnetic moment near vacancies. A theoretical study with the
      full-potential Density Functional Theory (DFT) approach (Wien2K code) have shown
      that when the dimension of MoS(2) is reduced from 2-D to 1-D the nonmagnetic semi
      conductor MoS(2) becomes a magnetic conductor. Our study has shown that a vacancy
      on the S-edge with 50% coverage intensifies the magnetization of the edge of the
      MoS(2) nanoribbon but such a vacancy on S-edge with 100% coverage causes this
      magnetic property to disappear. It is concluded that in both of them, there are
      positive or negative strong gradients of local magnetic moment near the vacancy.
      This may explain why lattice defects are essential for catalysis processes.

PMID- 20820731
TI  - Field-assisted synthesis of SERS-active silver nanoparticles using conducting
      polymers.
AB  - A gradient of novel silver nanostructures with widely varying sizes and
      morphologies is fabricated on a single conducting polyaniline-graphite (P-G)
      membrane with the assistance of an external electric field. It is believed that
      the formation of such a silver gradient is a synergetic consequence of the
      generation of a silver ion concentration gradient along with an electrokinetic
      flow of silver ions in the field-assisted model, which greatly influences the
      nucleation and growth mechanism of Ag particles on the P-G membrane. The produced
      silver dendrites, flowers and microspheres, with sharp edges, intersections and
      bifurcations, all present strong surface enhanced Raman spectroscopy (SERS)
      responses toward an organic target molecule, mercaptobenzoic acid (MBA). This
      facile field-assisted synthesis of Ag nanoparticles via chemical reduction
      presents an alternative approach to nanomaterial fabrication, which can yield a
      wide range of unique structures with enhanced optical properties that were
      previously inaccessible by other synthetic routes.

PMID- 20820732
TI  - Access to small size distributions of nanoparticles by microwave-assisted
      synthesis. Formation of Ag nanoparticles in aqueous carboxymethylcellulose
      solutions in batch and continuous-flow reactors.
AB  - This article examines the effect(s) of the 2.45-GHz microwave (MW) radiation in
      the synthesis of silver nanoparticles in aqueous media by reduction of the
      diaminesilver(i) complex, [Ag(NH(3))(2)](+), with carboxymethylcellulose (CMC) in
      both batch-type and continuous-flow reactor systems with a particular emphasis on
      the characteristics of the microwaves in this process and the size distributions.
      This microwave thermally-assisted synthesis is compared to a conventional heating
      (CH) method, both requiring a reaction temperature of 100 degrees C to produce
      the nanoparticles, in both cases leading to the formation of silver colloids with
      different size distributions. Reduction of the diaminesilver(i) precursor
      complex, [Ag(NH(3))(2)](+), by CMC depended on the solution temperature. Cooling
      the reactor during the heating process driven with 390-Watt microwaves (MW
      390W/Cool protocol) yielded silver nanoparticles with sizes spanning the range 1
      2 nm. By contrast, the size distribution of Ag nanoparticles with 170-Watt
      microwaves (no cooling; MW-170W protocol) was in the range 1.4-3.6 nm (average
      size approximately 3 nm). The overall results suggest the potential for a scale
      up process in the microwave-assisted synthesis of nanoparticles. Based on the
      present data, a flow-through microwave reactor system is herein proposed for the
      continuous production of silver nanoparticles. The novel flow reactor system
      (flow rate, 600 mL min(-1)) coupled to 1200-Watt microwave radiation generated
      silver nanoparticles with a size distribution 0.7-2.8 nm (average size ca. 1.5
      nm).

PMID- 20820733
TI  - Correlation between nanoscale surface potential and power conversion efficiency
      of P3HT/TiO2 nanorod bulk heterojunction photovoltaic devices.
AB  - This is an in depth study on the surface potential changes of P3HT/TiO(2) nanorod
      bulk heterojunction thin films. They are affected by interlayer structures, the
      molecular weight of P3HT, the processing solvents and the surface ligands on the
      TiO(2). The addition of an electron blocking layer and/or the hole blocking layer
      to the P3HT/TiO(2) thin film can facilitate charge carrier transport and result
      in a high surface potential shift. The changes in surface potential of
      multilayered bulk heterojunction films are closely correlated to their power
      conversion efficiency of photovoltaic devices. Changing ligand leads to the
      largest change in surface potential yielding the greatest effect on the power
      conversion efficiency. Merely changing the P3HT molecular weight is less
      effective and varying the processing solvents is least effective in increasing
      power conversion efficiency. The steric effect of the ligand has a large
      influence on the reduction of charge carrier recombination resulting in a great
      effect on the power conversion efficiency. By monitoring the changes in the
      surface potential of bulk heterojunction film of multilayer structures, we have
      obtained a useful guide for the fabrication of high performance photovoltaic
      devices.

PMID- 20820734
TI  - 3D ordered nanostructures fabricated by nanosphere lithography using an
      organometallic etch mask.
AB  - A new approach for fabricating porous structures on silicon substrates and on
      polymer surfaces, using colloidal particle arrays with a polymer mask of a highly
      etch-resistant organometallic polymer, is demonstrated. Monolayers of silica
      particles, with diameters of 60 nm, 150 nm, 300 nm, or 500 nm, were deposited
      either on a silicon substrate or on a surface coated with polyethersulfone (PES),
      and the voids of the arrays were filled with poly(ferrocenylmethylphenylsilane)
      (PFMPS). Argon ion sputtering removed the excess PFMPS on the particles which
      enabled removal of the particles with HF. Further pattern transfer steps with
      reactive ion etching for different time intervals provided structures in silicon
      or in a PES layer. Free-standing PES membranes exhibiting regular arrays of
      circular holes with high porosity were fabricated by using cellulose acetate as a
      sacrificial layer. The pores obtained on silicon substrates after etching were
      used as molds for nanoimprint lithography (NIL). A combination of the techniques
      of nanosphere lithography (NSL) and NIL has resulted in 3D nanostructures with a
      hemispherical shape (inherited from the nanoparticles) which was obtained both in
      silicon and in PMMA.

PMID- 20820735
TI  - Excitation profile of surface-enhanced Raman scattering in graphene-metal
      nanoparticle based derivatives.
AB  - Understanding energy transfer mechanisms in graphene derivatives is strongly
      motivated by the unusually interesting electronic properties of graphene, which
      can provide a template for the creation of novel nanostructured derivatives. From
      a synthetic point of view, it is highly attractive to envision being able to
      synthesize pristine graphene from precursors such as graphene oxide (GO). While
      this goal may be challenging over large length-scales, it is possible to generate
      regions of graphene at the nanoscale, confirmed by Raman spectroscopy or other
      methods. We describe an in situ method of nucleating gold or palladium
      nanoparticles in the presence of ethylene glycol as a reducing agent, while
      simultaneously reducing GO to graphene. The Au nanoparticles aid in spectroscopic
      characterization by both quenching fluorescence, allowing the graphene D and G
      bands to be quantified, and yielding a surface enhancement of about two orders of
      magnitude. We observe the excitation profile (488-785 nm) of the surface enhanced
      Raman spectrum (SERS) of graphene with Au nanoparticles adsorbed on the surface.
      Both the D and G bands display a resonance at approximately 593 nm (2.09 eV).
      This resonance may be interpreted as a combination of the plasmon resonance at
      548 nm and a likely contribution from charge transfer as well. In addition, we
      observe a stiffening of the G band compared with that of graphene. The mechanism
      of the SERS, whether plasmonic or charge transfer-based, enables insight into the
      electronic pathways available to the graphene-nanoparticle system. We discuss our
      results in the context of several existing studies of graphene-based
      nanostructure derivatives.

PMID- 20820736
TI  - Size exclusion chromatography of quantum dots by utilizing nanoparticle repelling
      surface of concentrated polymer brush.
AB  - We have found that the concentrated poly(methyl methacrylate) (PMMA) brush showed
      the very good nanoparticles (NPs) repellency in its good solvent, e.g.
      tetrahydrofuran (THF). Whereas the oil- and hydro-phobic (fluorinated),
      hydrophobic and hydrophilic surfaces adsorbed a lot of NPs. The repellency of NPs
      did not depend on the surface nature of the NPs. Preparing absorption free
      columns for size exclusion chromatography (SEC) may enable us to separate quantum
      dots (QDs) and NPs according to their size. By installing the concentrated PMMA
      brush into silica monolith columns, we tried to achieve SEC of QDs and NPs. The
      concentrated PMMA brush immobilized silica monolith columns were prepared by
      surface initiated atom transfer polymerization of MMA. As a result, we have
      succeeded in separating QDs according to their size. This SEC system may be
      advantageous because it can be used in good solvents of the brush regardless of
      the stability of the surface modifier layer on the NPs.

PMID- 20820737
TI  - Bidirectional mediation of TiO2 nanowires field effect transistor by dipole
      moment from purple membrane.
AB  - Bacteriorhodopsin-embedded purple membrane (bR-PM) is one of the most promising
      biomaterials for various bioelectronics applications. In this work, we
      demonstrate that a dipole bio-originated from bR-PM can bidirectionally mediate
      the performance of a bottom-contact TiO(2) nanowire field effect transistor (FET)
      for performance improvement. When negative gate voltage is applied, both transfer
      and output characteristics of the TiO(2) nanowire FET are enhanced by the bR-PM
      modification, resulting in a hole mobility increased by a factor of 2. The effect
      of the number of the deposited bR-PM layers on the normalized DeltaI(D) of the
      FET suggests that the additional electric field generated by the dipole moment
      natively existing in bR-PM actually boosts the performance of the TiO(2)
      nanowires FET.

PMID- 20820738
TI  - Hydrophilic TiO2 porous spheres anchored on hydrophobic polypropylene membrane
      for wettability induced high photodegrading activities.
AB  - TiO(2) porous nanospheres on polypropylene (PP) films (TiO(2)/PP composite) are
      produced at ambient temperature. Particle/pore size match up is the key anchoring
      point to overcome the low affinity between hydrophilic materials and hydrophobic
      materials. With the hydrophilic TiO(2) catalyst evenly dispersed on a hydrophobic
      surface, the aqueous solution will selectively skip the substrate and wet the
      catalysts. Such a wettability-induced smart system maximizes the degrading
      activity of the TiO(2) catalyst. In photodegrading reactions, the resulting
      TiO(2)/PP composite film exhibits a 10 times higher activity in flow-type setup
      than the same TiO(2) catalyst in a traditional batch-type setup.

PMID- 20820739
TI  - Nanoelectronic biosensors based on CVD grown graphene.
AB  - Graphene, a single-atom-thick and two-dimensional carbon material, has attracted
      great attention recently. Because of its unique electrical, physical, and optical
      properties, graphene has great potential to be a novel alternative to carbon
      nanotubes in biosensing. We demonstrate the use of large-sized CVD grown graphene
      films configured as field-effect transistors for real-time biomolecular sensing.
      Glucose or glutamate molecules were detected by the conductance change of the
      graphene transistor as the molecules are oxidized by the specific redox enzyme
      (glucose oxidase or glutamic dehydrogenase) functionalized onto the graphene
      film. This study indicates that graphene is a promising candidate for the
      development of real-time nanoelectronic biosensors.

PMID- 20820740
TI  - Uniform and controllable preparation of Au-Ag core-shell nanorods using
      anisotropic silver shell formation on gold nanorods.
AB  - Anisotropic and controllable silver shell formation on gold nanorods was realized
      in a micellar solution of hexadecytrimethylammonium chloride. Uniformity of the
      anisotropic Au-Ag core-shell particles contributes separation of four extinction
      bands. The ability to manipulate the shapes and sizes of these nanoparticles
      offers a wide-range control of the surface extinction from the visible to the
      near infrared regions (450-800 nm).

PMID- 20820741
TI  - Electrodeposition of thermally stable gold and silver nanoparticle ensembles
      through a thin alumina nanomask.
AB  - Hemispheric gold or silver nanoparticle (Au and AgNP) ensembles were
      electrodeposited on a smooth ITO electrode through a thin Al(2)O(3) nanomask. The
      nanomask reduced the deviation in the particle size and interparticle distance.
      The absorption peak based on localized surface plasmon resonance (LSPR) of the
      AuNP ensemble redshifted with increasing environmental refractive index,
      suggesting that the ensemble would be used as a LSPR sensor for chemical analysis
      and bioanalysis. The Al(2)O(3) nanomask prevented the Au and AgNPs from thermal
      coalescence even at 500 degrees C, and consequently, it improved thermal
      stabilities of nanoparticle ensembles. The ensembles exhibit LSPR-based
      absorption peak in the visible region, even after annealing. The nanomask allowed
      AgNPs, which are thermally and chemically less stable than AuNPs, to be coated
      with sintered TiO(2). The ITO/AgNP/TiO(2) electrode thus obtained functions as a
      photocathode on the basis of photoinduced electron transfer from silver
      nanoparticles to TiO(2).

PMID- 20820742
TI  - Schematic construction of flanged nanobearings from double-walled carbon
      nanotubes.
AB  - The performance of nanobearings constructed from double walled carbon nanotubes
      is considered to be crucially dependent on the initial rotational speed. Wearless
      rotation ceases for a nanobearing operating beyond a certain angular velocity. We
      propose a new design of nanobearings by manipulation of double walled carbon
      nanotubes leading to a flanged structure which possesses a built-in hindrance to
      the intertube oscillation without obstructing rotational motion. Through blocking
      the possible leakage path for rotational kinetic energy to the intertube
      oscillatory motion, the flanged bearing lowers its dissipative tendency when set
      into motion. Using molecular dynamics, it is shown that on account of its
      distinctive structure, the flanged bearing has superior operating characteristics
      and a broader working domain.

PMID- 20820743
TI  - Experimental and theoretical investigations on magnetic behavior of (Al,Co) co
      doped ZnO nanoparticles.
AB  - We present the structural and magnetic properties of Zn(0.95-x)Co(0.05)Al(x)O (x
      = 0.0 to 0.1) nanoparticles, synthesized by a novel sol-gel route followed by
      pyrolysis. Powder X-ray diffraction data confirms the formation of a single phase
      wurtzite type ZnO structure for all the compositions. The Zn(0.95)Co(0.05)O
      nanoparticles show diamagnetic behavior at room temperature. However, when Al is
      co-doped with Co with x = 0.0 to 0.10 in Zn(0.95-x)Co(0.05)Al(x)O, a systematic
      increase in ferromagnetic moment is observed up to x = 0.07 at 300 K. Above x =
      0.07 (e.g. for x = 0.10) a drastic decrease in ferromagnetic nature is observed
      which is concomitant with the segregation of poorly crystalline Al rich ZnO phase
      as evidenced from TEM studies. Theoretical studies using density functional
      calculations on Zn(0.95-x)Co(0.05)Al(x)O suggest that the partial occupancy of S2
      states leads to an increased double exchange interaction favoring the
      ferromagnetic ground states. Such ferromagnetic interactions are favorable beyond
      a threshold limit. At a high level doping of Al, the exchange splitting is
      reduced, which suppresses the ferromagnetic ordering.

PMID- 20820744
TI  - Intracellular trafficking of silicon particles and logic-embedded vectors.
AB  - Mesoporous silicon particles show great promise for use in drug delivery and
      imaging applications as carriers for second-stage nanoparticles and higher order
      particles or therapeutics. Modulation of particle geometry, surface chemistry,
      and porosity allows silicon particles to be optimized for specific applications
      such as vascular targeting and avoidance of biological barriers commonly found
      between the site of drug injection and the final destination. In this study, the
      intracellular trafficking of unloaded carrier silicon particles and carrier
      particles loaded with secondary iron oxide nanoparticles was investigated.
      Following cellular uptake, membrane-encapsulated silicon particles migrated to
      the perinuclear region of the cell by a microtubule-driven mechanism. Surface
      charge, shape (spherical and hemispherical) and size (1.6 and 3.2 microm) of the
      particle did not alter the rate of migration. Maturation of the phagosome was
      associated with an increase in acidity and acquisition of markers of late
      endosomes and lysosomes. Cellular uptake of iron oxide nanoparticle-loaded
      silicon particles resulted in sorting of the particles and trafficking to unique
      destinations. The silicon carriers remained localized in phagosomes, while the
      second stage iron oxide nanoparticles were sorted into multi-vesicular bodies
      that dissociated from the phagosome into novel membrane-bound compartments.
      Release of iron from the cells may represent exocytosis of iron oxide
      nanoparticle-loaded vesicles. These results reinforce the concept of multi
      functional nanocarriers, in which different particles are able to perform
      specific tasks, in order to deliver single- or multi-component payloads to
      specific sub-cellular compartments.

PMID- 20820745
TI  - Liposomal squalenoyl-gemcitabine: formulation, characterization and anticancer
      activity evaluation.
AB  - A new prodrug of gemcitabine, based on the covalent coupling of squalene to
      gemcitabine (GemSQ), has been designed to enhance the anticancer activity of
      gemcitabine, a nucleoside analogue active against a wide variety of tumors. In
      the present study, the feasibility of encapsulating GemSQ into liposomes either
      PEGylated or non-PEGylated has been investigated. The in vivo anticancer activity
      of these formulations has been tested on subcutaneous grafted L1210wt leukemia
      model and compared to that of free gemcitabine. The liposomal GemSQ appears to be
      a potential delivery system for the effective treatment of tumors.

PMID- 20820750
TI  - Immunoglobulin E-mediated sensitization to pine and beech dust in relation to
      wood dust exposure levels and respiratory symptoms in the furniture industry.
AB  - OBJECTIVES: Wood dust exposure may cause Immunoglobulin E (IgE)-mediated allergic
      diseases. Our objectives were to estimate pine and beech dust sensitization rates
      among woodworkers and a reference group, explore the association between exposure
      and sensitization and between sensitization and respiratory symptoms, and finally
      investigate the impact of proteinogenic specific IgE (sIgE) epitopes on
      respiratory symptoms. METHODS: In a Danish study among 52 furniture factories and
      2 reference factories, we evaluated the workers' asthma and rhinitis status using
      questionnaires and blood samples collected from 1506 woodworkers and 195
      references. Workers with asthma symptoms (N=298), a random study sample (N=399)
      and a random rhinitis sample (N=100) were evaluated for IgE-mediated
      sensitization to pine and beech dust. RESULTS: The prevalence of pine and beech
      sensitization among current woodworkers was 1.7 and 3.1%, respectively. No
      differences in sensitization rates were found between woodworkers and references,
      but the prevalence of wood dust sensitization was dose-dependently associated
      with the current level of wood dust exposure. No relation was observed between
      wood dust sensitization per se and respiratory symptoms. Only symptomatic
      subjects had proteinogenic IgE epitopes to pine. Increased odds ratios for sIgE
      based on proteinogenic epitopes to beech and respiratory symptoms were found,
      although they were not statistically significant. CONCLUSIONS: Sensitization
      rates to pine and beech were the same for woodworkers and references but
      dependent on the current wood dust exposure level. The importance of beech and
      pine wood sensitization is limited, but may be of clinical significance for a few
      workers if the IgE epitopes are proteinogenic.

PMID- 20820751
TI  - Mitochondrial metabolic adaptation in right ventricular hypertrophy and failure.
AB  - Right ventricular failure (RVF) is the leading cause of death in pulmonary
      arterial hypertension (PAH). Some patients with pulmonary hypertension are
      adaptive remodelers and develop RV hypertrophy (RVH) but retain RV function;
      others are maladaptive remodelers and rapidly develop RVF. The cause of RVF is
      unclear and understudied and most PAH therapies focus on regressing pulmonary
      vascular disease. Studies in animal models and human RVH suggest that there is
      reduced glucose oxidation and increased glycolysis in both adaptive and
      maladaptive RVH. The metabolic shift from oxidative mitochondrial metabolism to
      the less energy efficient glycolytic metabolism may reflect myocardial ischemia.
      We hypothesize that in maladaptive RVH a vicious cycle of RV ischemia and
      transcription factor activation causes a shift from oxidative to glycolytic
      metabolism thereby ultimately promoting RVF. Interrupting this cycle, by reducing
      ischemia or enhancing glucose oxidation, might be therapeutic. Dichloroacetate, a
      pyruvate dehydrogenase kinase inhibitor, has beneficial effects on RV function
      and metabolism in experimental RVH, notably improving glucose oxidation and
      enhancing RV function. This suggests the mitochondrial dysfunction in RVH may be
      amenable to therapy. In this mini review, we describe the role of impaired
      mitochondrial metabolism in RVH, using rats with adaptive (pulmonary artery
      banding) or maladaptive (monocrotaline-induced pulmonary hypertension) RVH as
      models of human disease. We will discuss the possible mechanisms, relevant
      transcriptional factors, and the potential of mitochondrial metabolic
      therapeutics in RVH and RVF.

PMID- 20820752
TI  - Pattern recognition of viral nucleic acids by RIG-I-like helicases.
AB  - Recognition of pathogenic microbes by the innate immune system is based on the
      principle of pathogen-associated molecular patterns (PAMPs). These are conserved
      molecular structures that are present in the pathogen but not in the host. Cells
      of the innate immune system or, in some cases, virtually all cells of our body
      express receptors that are able to specifically recognize PAMPs and trigger the
      appropriate responses including the production of cytokines. In the case of
      viruses, an interesting complication exists: Viruses use the host's cellular
      metabolism and building blocks to replicate. As a consequence, protein
      modifications, lipid or carbohydrate configurations restricted to viruses do not
      exist. Instead, parts of the innate immune system have evolved to detect viral
      nucleic acids mainly by virtue of their (non-physiological) localization and
      structure. Understanding the molecules involved in anti-viral defence and the
      patterns they recognize will allow harnessing them for therapeutic strategies
      targeting viral and autoimmune diseases and tumours. This review presents
      important recent advances in understanding intracellular recognition of nucleic
      acid patterns by the innate immune system.

PMID- 20820754
TI  - Changes in rates, methods and characteristics of suicide attempters over a 15
      year period: comparison between Stockholm, Sweden, and Wurzburg, Germany.
AB  - PURPOSE: To investigate age and sex-specific changes in rates, methods used and
      characteristics of suicide attempters receiving medical care, over a 15-year
      period in two European WHO catchment areas (Stockholm, Sweden; and Wurzburg,
      Germany). METHODS: The data for this study were obtained from the WHO/EURO
      Multicentre Study on Suicidal Behaviour for the period 1989-2003. Sex-specific,
      person-based suicide attempt rates were calculated for each year separately for
      the age groups 15-24 and 25 or above. The Chi-square test for trend was applied
      to estimate changes in proportions of socio-demographic and socio-economic
      variables. RESULTS: Significantly, increasing trends in suicide attempt rates
      occurred in young females, and in males and females aged 25 or above in Wurzburg.
      On the contrary, men 25 years and above showed a significant decrease in suicide
      attempt rates in Stockholm. Young females in Wurzburg tended to use less violent
      methods for their attempts whereas in Stockholm young females were increasingly
      inclined to attempt suicide using violent methods. In Stockholm, young female
      suicide attempters tended to be more often economically inactive, particularly
      due to an increasing proportion of students. Young females in Wurzburg were often
      less well educated, as were their young male counterparts. This contrasted with
      trends in the education of men and women of 25 or above in Stockholm.
      CONCLUSIONS: The results of this study suggest temporal changes in trends,
      methods used and in the social profile of suicide attempters.

PMID- 20820753
TI  - Association of glycaemia with lipids in adults with type 1 diabetes: modification
      by dyslipidaemia medication.
AB  - AIMS/HYPOTHESIS: Hyperglycaemia and dyslipidaemia are common metabolic
      abnormalities in adults with type 1 diabetes and both increase cardiovascular
      disease (CVD) risk. The hypothesis of this study was that change in HbA(1c) over
      6 years would be associated with change in fasting lipids in adults with type 1
      diabetes. METHODS: The Coronary Artery Calcification in Type 1 Diabetes (CACTI)
      study examined 652 patients with type 1 diabetes (54% female); 559 and 543 had
      follow-up visits at 3 and 6 years. Baseline age (mean +/- SD) was 37 +/- 9 years,
      diabetes duration 23 +/- 9 years, and HbA(1c) 8.0 +/- 1.3%. Use of dyslipidaemia
      medication was 17%, 32%, and 46% at the three visits. Separate longitudinal mixed
      models were fitted to examine the relationship between change in HbA(1c) and
      change in fasting total cholesterol (TC), HDL-cholesterol (HDL-c), LDL
      cholesterol (LDL-c), log triacylglycerols (TG), and non-HDL-cholesterol (non-HDL
      c). Because of an interaction between dyslipidaemia medication use and
      association of HbA(1c) with lipids, results were stratified by dyslipidaemia
      medication use. RESULTS: Among patients not using dyslipidaemia medication, a
      higher HbA(1c) was associated with significantly worse levels of the lipids TC,
      LDL-c, TG and non-HDL-c (per 1% change in HbA1c, TC 0.101 mmol/l, 95% CI 0.050,
      0.152; LDL-c 0.103 mmol/l, 95% CI 0.058, 0.148; TG 0.052 mmol/l, 95% CI 0.024,
      0.081; and non-HDL-c 0.129 mmol/l, 95% CI 0.078, 0.180) but not HDL-c (-0.20
      mmol/l, 95% CI -0.047, 0.007). The associations between HbA(1c) and any lipid
      outcome among those on dyslipidaemia medication were in the same direction, but
      attenuated compared with persons not on medication. CONCLUSIONS/INTERPRETATION:
      Change in HbA(1c) is significantly associated with change in fasting lipids, but
      dyslipidaemia medications may be required to optimise lipid and cardiovascular
      health.

PMID- 20820755
TI  - Suicidal behavior among immigrants.
AB  - INTRODUCTION: This paper explores the association between suicidal behavior and
      immigrant status among Israeli residents from the former USSR (FSU). METHOD: The
      Israeli component of the World Mental Health Survey (INHS) provided information
      on suicide ideations, plans and attempts. The INHS samples included Israel-born
      Jews (n = 2,114) and post-1990 immigrants from the FSU (n = 814). Data on
      completed suicide were extracted from the countrywide report of the Ministry of
      Health. RESULTS: The controlled lifetime rates of suicidal behavior among FSU
      immigrants were significantly higher than among their Israel-born counterparts. A
      higher risk was found in the first years following immigration among young adults
      with higher education and without a spouse. Completed suicide rates were higher
      among the FSU immigrants than in the general Israeli population with the largest
      risk among young-adult immigrant men. DISCUSSION: The findings are consistent
      with previous studies and are discussed in the context of both suicide rates in
      the country of origin and migratory stressors. Preventive measures are suggested.

PMID- 20820756
TI  - The short-term outcome of depressive disorder in adolescents attending primary
      care: a cohort study.
AB  - BACKGROUND: Depressive disorder is common amongst adolescents attending primary
      care, but little is known about its time course. AIM: To determine the 6-month
      outcome of depressive disorder in adolescent primary care attendees with regard
      to the time to recovery from (1) the date of index GP consultation and (2) the
      date of depressive episode onset, and to identify risk factors associated with
      time to recovery. METHOD: A prospective cohort study of 13-18-year-olds attending
      a general practice in northwest London. Attendees were screened for depressive
      disorder at consultation: high scorers underwent a psychiatric research
      interview. Six months later, adolescents who were depressed at consultation were
      interviewed using a research psychiatric follow-up interview. RESULTS: Of the 274
      young people who completed the baseline questionnaires, 26 had a depressive
      disorder at consultation; over 50% failed to recover by the 6-month follow-up.
      Median episode duration from illness onset was 13 months. Multivariate cox
      regression showed that fewer positive life events and more physical symptoms
      predicted a longer time to recovery from consultation. Younger age, fewer recent
      positive life events and more depressive symptoms predicted a longer time to
      recovery from illness onset. CONCLUSIONS: Adolescent depressive disorders in
      general practice attendees are persistent, highlighting the appropriateness of
      intervention.

PMID- 20820758
TI  - Calcium channel subtypes for cholinergic and nonadrenergic noncholinergic
      neurotransmission in isolated guinea pig trachea.
AB  - The Ca(2+) channel subtypes in the neurotransmission of isolated guinea pig
      trachea were elucidated by monitoring the effects of specific Ca(2+) channel
      blockers on cholinergic contractions and nonadrenergic noncholinergic (NANC)
      relaxation elicited by electrical field stimulation (EFS). In isolated guinea pig
      trachea, cholinergic contractile responses to low- and high-frequency EFS were
      inhibited by the selective N-type calcium channel blocker, omega-conotoxin MVIIA.
      omega-Agatoxin IVA (a selective P-type blocker), omega-conotoxin MVIIC (a
      nonselective N-, Q-, and P-type blocker), and nifedipine (a selective L-type
      blocker) were ineffective, whereas Ni(2+) (a T- and R-type blocker) facilitated
      cholinergic contractions and produced a late contracture when its concentration
      exceeded 30 MUM. The more the concentration of Ni(2+) increased, the greater the
      number of incidences and the late contracture areas which occurred. Late
      contracture did not seem to be due to the effects of acetylcholine, tachykinins,
      or other polypeptides, but disappeared in the absence of indomethacin. The NANC
      relaxant responses elicited by the low- and high-frequency EFS were inhibited by
      omega-conotoxin MVIIA or Ni(2+), but unaffected by omega-Agatoxin IVA, omega
      conotoxin MVIIC, and nifedipine. In the absence of indomethacin, Ni(2+) did not
      alter the omega-conotoxin MVIIA (100 nM)-resistant component of cholinergic
      contraction, but significantly further inhibited that of NANC relaxation. These
      results suggest that in isolated guinea pig trachea, cholinergic contraction is
      regulated by N-type calcium channels which may mask T- and R-type calcium
      channels and may be co-modulated by both, while NANC relaxation is mainly and
      independently controlled by N-, T-, and R-type calcium channels.

PMID- 20820759
TI  - Angiotensin II type 1 receptor blockers improve insulin sensitivity in patients
      with schizophrenia being treated with olanzapine.
AB  - RATIONALE: Olanzapine (OLZ) is known to cause weight gain and metabolic
      disturbances, which may have serious implications with respect to medical
      comorbidities such as metabolic syndrome and insulin resistance. OBJECTIVES: The
      aim of this study was to evaluate the effects of two angiotensin II type 1
      receptor blockers (ARBs) which are widely used as antihypertensive agents,
      valsartan (VAL) and telmisartan (TEL), on insulin resistance in patients with
      schizophrenia treated with OLZ. METHODS: Thirty inpatients with schizophrenia
      with OLZ monotherapy over 8 weeks participated in this study. To assess insulin
      resistance, the homeostasis model assessment of insulin resistance (HOMA-IR),
      fasting plasma glucose (PG) levels and immunoreactive insulin (IRI) levels were
      measured [HOMA-IR = fasting PG level (mmol/L) x fasting IRI level (MUU/ml)/22.5].
      VAL add-on treatment was performed in insulin-resistant patients (HOMA-IR > 1.6)
      for 12 weeks. After a 12-week VAL washout period, TEL add-on treatment was
      carried out for 12 weeks. The effects of ARBs on insulin resistance and other
      metabolic variables were assessed. RESULTS: In all 30 patients, both body mass
      index and abdominal circumference were strongly correlated with HOMA-IR. Twelve
      patients showed high HOMA-IR and were deemed to be insulin resistant. Add-on
      therapy of VAL and TEL resulted in a significant decrease in fasting IRI levels
      and HOMA-IR. No differences in any effects were observed between VAL and TEL. No
      adverse effects of either ARBs were observed in this study. CONCLUSIONS: ARBs for
      patients treated with OLZ improved insulin sensitivity and attenuated insulin
      resistance.

PMID- 20820760
TI  - How automatic is the hand's automatic pilot? Evidence from dual-task studies.
AB  - The ability to correct reaching movements for changes in target position has been
      described as the hand's 'automatic pilot'. These corrections are preconscious and
      occur by default in double-step reaching tasks, even if the goal is to react to
      the target jump in some other way, for instance by stopping the movement (STOP
      instruction). Nonetheless, corrections are strongly modulated by conscious
      intention: participants make more corrections when asked to follow the target (GO
      instruction) and can suppress them when explicitly asked not to follow the target
      (NOGO instruction). We studied the influence of a cognitively demanding (auditory
      1-back) task upon correction behaviour under GO, STOP and NOGO instructions.
      Correction rates under the STOP instruction were unaffected by cognitive load,
      consistent with the assumption that they reflect the default behaviour of the
      automatic pilot. Correction rates under the GO instruction were also unaffected,
      suggesting that minimal cognitive resources are required to enhance online
      correction. By contrast, cognitive load impeded the ability to suppress online
      corrections under the NOGO instruction. These data reveal a constitutional bias
      in the automatic pilot system: intentional suppression of the default correction
      behaviour is cognitively demanding, but enhancement towards greater
      responsiveness is seemingly effortless.

PMID- 20820762
TI  - Implicit motor learning from target error during explicit reach control.
AB  - Many studies have shown adapted reaching in the face of altered visual feedback.
      These studies typically involve iterative corrections to the error induced by the
      perturbation until relatively normal performance is achieved. Here, we
      investigate whether adaptation (indexed by aftereffects) can occur when direct
      corrections to a target are inhibited by giving participants an explicit reach
      task. During the exposure phase of our study, participants were instructed to
      undershoot a target that imperceptibly moved between movement onset and movement
      end. The size of the target displacement was gradually increased, while the
      instructed undershoot distance was equivalently increased, such that participants
      were, unknowingly, aiming to the same location throughout exposure. When
      participants were subsequently instructed to aim at the target during the post
      test, they overshot the target, suggesting that adaptation had occurred in the
      presence of an explicit task and in the absence of direct corrections to the
      target perturbation.

PMID- 20820761
TI  - The conjugacy of the vestibulo-ocular reflex evoked by single labyrinth
      stimulation in awake monkeys.
AB  - It is well known that the vestibulo-ocular reflex (VOR) is conjugate when
      measured in the dark with minimal vergence. But the neural basis of the VOR
      conjugacy remains to be identified. In the present study, we measured the VOR
      conjugacy during single labyrinth stimulation to examine whether the VOR
      conjugacy depends on reciprocal stimulation of the two labyrinths. There are
      conflicting views on this issue. First, since the vestibular signals carried by
      the ascending tract of Deiters' are distributed exclusively to the motoneurons of
      the ipsilateral eye, the neural innervations after single labyrinth stimulation
      are not symmetrical for the two eyes. Thus, single labyrinth stimulation may
      generate disjunctive VOR responses. Second, the only published study on this
      issue was an electrooculography (EOG) study that reported disjunctive VOR
      responses during unilateral caloric irrigation (Wolfe in Ann Otol 88:79-85,
      1979). Third, the VOR during unilateral caloric stimulation performed in clinical
      vestibular tests is routinely perceived to be conjugate. To resolve these
      conflicting views, the present study examined the VOR conjugacy during single
      labyrinth stimulation by recording binocular eye position signals in awake
      monkeys with a search coil technique. In contradiction to the previous EOG study
      and the prediction based on the asymmetry of the unilateral brainstem VOR
      circuits, we found that the VOR during unilateral caloric irrigation was
      conjugate over a wide range of conditions. We conclude that the net neural
      innervations received by the two eyes are symmetrical after single labyrinth
      stimulation, despite the apparent asymmetry in the unilateral VOR pathways. A
      novel role for the ascending tract of Deiters' in the VOR conjugacy is proposed.

PMID- 20820763
TI  - Does planning a different trajectory influence the choice of grasping points?
AB  - We examined whether the movement path is considered when selecting the positions
      at which the digits will contact the object's surface (grasping points). Subjects
      grasped objects of different heights but with the same radius at various
      locations on a table. At some locations, one digit crossed to the side of the
      object opposite of where it started. In doing so, it moved over a short object
      whereas it curved around a tall object. This resulted in very different paths for
      different objects. Importantly, the selection of grasping points was unaffected.
      That subjects do not appear to consider the path when selecting grasping points
      suggests that the grasping points are selected before planning the movements
      towards those points.

PMID- 20820764
TI  - The expression of IL-6 by osteoblasts is increased in healthy elderly
      individuals: stimulated proliferation and differentiation are unaffected by age.
AB  - Increasing age is associated with reduced bone mineral content and increased risk
      of fractures. This is caused by a relative insufficiency of osteoblasts compared
      with osteoclasts. We therefore wanted to examine the potential differences in
      proliferation, differentiation, and expression of cytokines between human
      osteoblasts (hOBs) obtained from young and elderly individuals. Cultures of hOBs
      were obtained from 11 elderly (73-85 years) and 15 young (21-27 years) healthy
      individuals. The cells were stimulated with hGH, IGF-I, hGH + IGF-I, and TGF
      beta1. Proliferation was evaluated by thymidine incorporation, and
      differentiation was evaluated by alkaline phosphatase, OPG, and PINP production.
      Expression of IL-6, TGF-beta1, OPG, and RANKL was investigated using real-time
      PCR and three carefully selected housekeeping genes. Combined stimulation with
      hGH and IGF-I increased proliferation without differences between hOBs obtained
      from young and elderly individuals. hOBs from young individuals responded to
      stimulation with vitamin D with a more pronounced increase in alkaline
      phosphatase: 107 +/- 17% vs. 43 +/- 5%, P < 0.01. Stimulation with TGF-beta1
      decreased OPG production by hOBs from elderly individuals but not from young
      individuals, P < 0.05. hOBs from elderly individuals expressed significantly
      higher amounts of IL-6 mRNA (P < 0.05) and less OPG and TGF-beta1 mRNA (P = 0.08
      and P = 0.08, respectively) compared with hOBs from young individuals. In
      conclusion, hOBs from elderly individuals express more IL-6 mRNA and less OPG and
      TGF-beta1 mRNA than hOBs from young individuals. This could partly explain the
      reduced bone mass and increased fracture risk seen in the elderly. hOBs from
      young and elderly individuals responded similarly to short-term stimulation of
      proliferation and differentiation.

PMID- 20820765
TI  - Imaging tests in determination of brain death.

PMID- 20820767
TI  - The issue of whether studies involving off-label use of new devices need to be
      replaced by controlled studies.

PMID- 20820768
TI  - Detection of functional overlapping genes: simulation and case studies.
AB  - As far as protein-coding genes are concerned, there is a non-zero probability
      that at least one of the five possible overlapping sequences of any gene will
      contain an open-reading frame (ORF) of a length that may be suitable for coding a
      functional protein. It is, however, very difficult to determine whether or not
      such an ORF is functional. Recently, we proposed a method that predicts
      functionality of an overlapping ORF if it can be shown that it has been subject
      to purifying selection during its evolution. Here, we use simulation to test this
      method under several conditions and compare it with the method of Firth and
      Brown. We found that under most conditions, our method detects functional
      overlapping genes with higher sensitivity than Firth and Brown's method, while
      maintaining high specificity. Further, we tested the hypothesis that the two
      aminoacyl tRNA synthetase classes have originated from a pair of overlapping
      genes. A central piece of evidence ostensibly supporting this hypothesis is the
      assertion that an overlapping ORF of a heat-shock protein-70 gene, which exhibits
      some similarity to class 2 aminoacyl tRNA synthetases, is functional. We found
      signature of purifying selection only in highly divergent sequences, suggesting
      that the method yields false-positives in high sequence divergence and that the
      overlapping ORF is not a functional gene. Finally, we examined three cases of
      overlap in the human genome. We find varying signatures of purifying selection
      acting on these overlaps, raising the possibility that two of the overlapping
      genes may not be functional.

PMID- 20820769
TI  - Ventriculocoronary artery connections with the hypoplastic left heart: a 4-year
      prospective study: incidence, echocardiographic and clinical features.
AB  - Ventriculocoronary connections (VCCs), also called sinusoids, occur with
      hypoplastic left heart (HLH). Previous reports are limited to case reports,
      pathologic series, and surgical series with limited detail, which may
      underestimate the incidence and overestimate the severity of VCCs in HLH. A study
      was conducted to determine the incidence VCCs in HLH, their effect on survival,
      and their echocardiographic and clinical features. The echocardiograms and
      medical records of 100 consecutive neonatal HLH cases were analyzed. All had an
      aortic and a mitral valve diameter and a left ventricular (LV) volume less than Z
      3. For palliation, Norwood, Sano, or hybrid procedures were used, and if the
      patient was alive, subsequent bidirectional Glenn and extracardiac Fontan
      procedures were applied. Cases were classified as manifesting mitral and aortic
      atresia (MAAA), mitral and aortic stenosis (MSAS), or mitral stenosis and aortic
      atresia (MSAA). All other diagnoses or any case with additional cardiac anomalies
      were excluded from the study. Overall, VCCs were found in 15% of the cases. They
      occurred in 56% of the MSAA subtype cases and were not statistically associated
      with a high mortality rate. However, in one case, large and multiple VCCs
      definitely caused or contributed to early death. All VCCs had a transmyocardial
      course, a turbulent color-Doppler flow, and a dominant usually retrograde
      systolic coronary artery flow pattern. The VCCs were associated (p < 0.05) with
      MSAA, endocardial fibroelastosis, and ascending aortic size less than 2 mm. As
      shown by the findings, 15% of the HLH patients had MSAA with VCCs. Unless the
      VCCs were large or extensive, they did not contribute to mortality. Detailed
      echocardiographic analysis of VCCs in HLH was feasible. Recent reports emphasize
      more severe cases.

PMID- 20820771
TI  - Symptomatic hip plica: MR arthrographic and arthroscopic correlation.
AB  - Two cases of unilateral hip pain are reported in which MR arthrography
      demonstrated a prominent band medial to the ligamentum teres, running in the AP
      direction, consistent with a hip plica. Both patients underwent hip arthroscopy
      with resection of the band. No labral tear or additional intra-articular
      pathological features was identified in either case. Both patients became
      asymptomatic following surgery and have remained such. The pathology report
      demonstrated the specimens to be a synovial band with fibroconnective tissue.
      This is the first MR arthrographic report of the identification and resection of
      a symptomatic hip plica. The symptomatic plica may represent an alternative
      diagnosis for mechanical hip pain.

PMID- 20820770
TI  - Comparative analysis of nonaspanin protein sequences and expression studies in
      zebrafish.
AB  - Nonaspanins constitute a family of proteins, also called TM9SF, characterized by
      a large non-cytoplasmic domain and nine putative transmembrane domains. This
      family is highly conserved through evolution and comprises three members in
      Saccharomyces cerevisiae, Dictyostelium discoideum, and Drosophila melanogaster,
      and four members are reported in mammals (TM9SF1-TM9SF4). Genetic studies in
      Dictyostelium and Drosophila have shown that TM9SF members are required for
      adhesion and phagocytosis in innate immune response, furthermore, human TM9SF1
      plays a role in the regulation of autophagy and human TM9SF4 in tumor
      cannibalism. Here we report that the zebrafish genome encodes five members of
      this family, TM9SF1-TM9SF5, which show high level of sequence conservation with
      the previously reported members. Expression analysis in zebrafish showed that all
      members are maternally expressed and continue to be present throughout
      embryogenesis to adults. Gene expression could not be regulated by pathogen
      associated molecular patterns such as LPS, CpG, or Poly I:C. By bioinformatic
      analyses of 80 TM9SF protein sequences from yeast, plants, and animals, we
      confirmed a very conserved protein structure. An evolutionary conserved
      immunoreceptor tyrosine-based inhibition motif has been detected in the
      cytoplasmic domain between transmembrane domain (TM) 7 and TM8 in TM9SF1, TM9SF2,
      TM9SF4 and TM9SF5, and at the extreme C-terminal end of TM9SF4. Finally, a
      conserved TRAF2 binding domain could also be predicted in the cytoplasmic regions
      of TM9SF2, TM9SF3, TM9SF4, and TM9SF5. This confirms the hypothesis that TM9SF
      proteins may play a regulatory role in a specific and ancient cellular mechanism
      that is involved in innate immunity.

PMID- 20820772
TI  - Inadvertent intra-articular lumbar facet joint injection during fluoroscopically
      guided interlaminar epidural steroid injection.
AB  - OBJECTIVE: Inadvertent lumbar facet joint injection during an interlaminar
      epidural steroid injection (ESI) is rare when using the loss-of-resistance
      technique. The pattern of contrast material on the lateral view can mimic that of
      a successful ESI. The purpose of this study is to illustrate the imaging features
      of this event. MATERIALS AND METHODS: From 2001 to 2009, 6,631 interlaminar
      lumbar ESIs were performed. Cases in which facet joint injection was recognized
      by the radiologist were identified by a text search of the report for the term
      "facet" and corroborated by review of the case images and the patients' medical
      records. RESULTS: Forty-two positive events were identified. Imaging features are
      characteristic and include sigmoid-shaped area of contrast material projecting
      over the posterior elements on the lateral view and an ovoid area of contrast
      material projecting over the facet joints on the anteroposterior (AP) view.
      Thirty-one out of 42 events were recognized by the operator during the procedure.
      In 17 cases, the final images documented the appropriate location of the needle
      tip within the epidural space. In 9 cases, simultaneous epidural and facet joint
      injection occurred. In 16 cases, epidural contrast material was not documented.
      CONCLUSION: Lumbar facet joint injection has a characteristic appearance and can
      be distinguished from epidural injection. However, since this event can simulate
      the appearance of a successful ESI, it may be unrecognized during the procedure.
      Therefore, the true incidence is likely higher than that suggested by this study.
      Recognizing the imaging features of this event permits the operator to further
      manipulate the needle tip and increase the success rate of ESIs.

PMID- 20820773
TI  - Synovial plicae of the hip: evaluation using MR arthrography in patients with hip
      pain.
AB  - OBJECTIVE: The appearance and distribution of the intra-articular plicae of the
      hip have been addressed in few reports in the anatomic and radiological
      literature. This study aims to determine the prevalence of visible synovial hip
      plicae using MR arthrography and to measure the association of visible synovial
      hip plicae with MR arthrographic diagnosis of labral tears, femoroacetabular
      impingement, and osteoarthritis. MATERIALS AND METHODS: Following institutional
      review board approval, 63 direct MR arthrographic examinations of the hip in 61
      patients with a clinical history of hip pain were retrospectively reviewed by two
      experienced musculoskeletal radiologists in consensus. The following variables
      were measured using a binary system (0 = absent; 1 = present): labral plica, neck
      plica, ligamental plica, labral tear, femoroacetabular impingement, and
      osteoarthritis. The surgical reports and arthroscopic images of 10 patients were
      reviewed. Statistical analysis was performed using the Fisher's exact test.
      RESULTS: In all 63 cases at least one plica was visualized on MR-arthrographic
      images. Labral, neck, and ligamental plicae were found with a prevalence of 76,
      97, and 78%, respectively. There was no statistically significant association
      between the presence of labral tears, femoroacetabular impingement, and
      osteoarthritis among patients with visible labral, neck, and ligamental plicae.
      The prevalence of labral tears, femoroacetabular impingement, and osteoarthritis
      in our patient population was 79, 28, and 28%, respectively. The presence of
      intra-articular plicae was the only MR-arthrographic finding in 5 of our 63
      symptomatic cases. CONCLUSION: Visible labral, neck, and/or ligamental plicae are
      highly prevalent on MR-arthrographic images of the hip performed in the setting
      of hip pain. There was no statistically significant association between the
      presence of labral tears, femoroacetabular impingement, and osteoarthritis and
      visible labral, neck, and ligamental plicae.

PMID- 20820774
TI  - Deep rectosigmoid endometriosis: "mushroom cap" sign on T2-weighted MR imaging.
AB  - PURPOSE: The purpose of this study is to evaluate the "mushroom cap" sign on T2
      weighted MR imaging in patients with submucosal tumors in the rectosigmoid colon.
      METHODS: From January 2001 to August 2009, 12 patients with four different
      diseases presenting or mimicking submucosal tumors in the rectosigmoid colon
      underwent colonic resection. All patients with deep endometriosis (n = 6),
      gastrointestinal stromal tumor (n = 4), metastasis from ovary cancer (n = 1), and
      carcinoid tumor (n = 1) had either an MRI of the rectum or pelvis before surgery.
      We evaluated the MRI findings and compared them with the macroscopic and
      microscopic observations in the resected specimens. RESULTS: In all six cases of
      deep endometriosis, a characteristic "mushroom cap" shaped appearance was found
      on T2-weighted MR imaging. Heterogeneous low signal intensity of the hypertrophic
      muscularis propria, covered with high signal intensity of the mucosa and
      submucosa on T2-weighted MR images, looked like a "mushroom cap" with the pattern
      of intraluminal endophytic growth. In histological findings, deep endometriosis
      involved the submucosa (n = 4) or mucosa (n = 2). The "mushroom cap" sign was not
      present in any of the six other tumors. CONCLUSION: The "mushroom cap" sign on T2
      weighted MR imaging may be a characteristic sign for diagnosing deep rectosigmoid
      endometriosis.

PMID- 20820775
TI  - Toll-like receptor-7 agonist administered subcutaneously in a prolonged dosing
      schedule in heavily pretreated recurrent breast, ovarian, and cervix cancers.
AB  - BACKGROUND: The primary objective was to study the antitumor activity of
      prolonged subcutaneous dosing of systemic 852A, a Toll-like receptor-7 agonist
      (TLR-7), in recurrent breast, ovarian and cervix cancer. Secondary objectives
      included assessment of safety and immune system activation. METHODS: Adults with
      recurrent breast, ovarian or cervix cancer failing multiple therapies received
      0.6 mg/m(2) of 852A subcutaneously twice weekly for 12 weeks. Doses increased by
      0.2 mg/m(2)/week to a maximum of 1.2 mg/m(2). Serum was collected to assess
      immune activation. RESULTS: Fifteen patients enrolled: 10 ovarian, 2 cervix and 3
      breast. Three completed all 24 injections. There were two grade 2 (decreased
      ejection fractions), nine grade 3 (1 cardiovascular, 1 anorexia, 3 dehydration, 2
      infections, 2 renal) and two grade 4 (hepatic and troponin elevation)
      unanticipated toxicities. Cardiac toxicities included three cardiomyopathies (2
      asymptomatic) and one stress-related non-ST elevated myocardial infarction. Five
      patients discontinued therapy due to possibly associated side effects. One who
      had stable disease (SD) following 24 doses received 17 additional doses. A cervix
      patient with SD following 24 doses received chemotherapy after progressing 3
      months later, and remains disease free at 18 months. Immune activation, as
      evidenced by increased IP-10 and IL-1ra, was observed. CONCLUSIONS: In this first
      human experience of a TLR-7 agonist delivered subcutaneously using a prolonged
      dosing schedule, 852A demonstrated sustained tolerability in some patients.
      Clinical benefit was modest, but immune activation was seen suggesting further
      study of antitumor applications is warranted. Because of cardiac toxicity; 852A
      should be used cautiously in heavily pretreated patients.

PMID- 20820776
TI  - Alternative Ii-independent antigen-processing pathway in leukemic blasts involves
      TAP-dependent peptide loading of HLA class II complexes.
AB  - During HLA class II synthesis in antigen-presenting cells, the invariant chain
      (Ii) not only stabilizes HLA class II complexes in the endoplasmic reticulum, but
      also mediates their transport to specialized lysosomal antigen-loading
      compartments termed MIICs. This study explores an alternative HLA class II
      presentation pathway in leukemic blasts that involves proteasome and transporter
      associated with antigen processing (TAP)-dependent peptide loading. Although HLA
      DR did associate with Ii, Ii silencing in the human class II-associated invariant
      chain peptide (CLIP)-negative KG-1 myeloid leukemic cell line did not affect
      total and plasma membrane expression levels of HLA-DR, as determined by western
      blotting and flow cytometry. Since HLA-DR expression does require peptide
      binding, we examined the role of endogenous antigen-processing machinery in HLA
      DR presentation by CLIP(-) leukemic blasts. The suppression of proteasome and TAP
      function using various inhibitors resulted in decreased HLA-DR levels in both
      CLIP(-) KG-1 and ME-1 blasts. Simultaneous inhibition of TAP and Ii completely
      down-modulated the expression of HLA-DR, demonstrating that together these
      molecules form the key mediators of HLA class II antigen presentation in leukemic
      blasts. By the use of a proteasome- and TAP-dependent pathway for HLA class II
      antigen presentation, CLIP(-) leukemic blasts might be able to present a broad
      range of endogenous leukemia-associated peptides via HLA class II to activate
      leukemia-specific CD4(+) T cells.

PMID- 20820777
TI  - A cementless elastic monoblock socket in young patients: a ten to 18-year
      clinical and radiological follow-up.
AB  - The survival of acetabular components depends on several factors: wear,
      osteolysis and septic or aseptic loosening. Osteolysis seems to be the main cause
      for concern in cementless arthroplasties. Acetabular osteolysis results from
      particle debris and segmental unloading of acetabular bone by rigid sockets. We
      investigated a cementless elastic monoblock socket with regard to acetabular
      osteolysis and aseptic loosening in a cohort of young patients. We evaluated 158
      hip arthroplasties with a minimum follow-up of ten years (ten to 18) and a mean
      age of 42 years (18-50). The overall revision rate at 14 years was 80% with a 98%
      survival rate for aseptic loosening. The mean polyethylene wear rate was 0.11
      mm/year. Progressive acetabular osteolysis was seen in 3% of patients evaluated.
      In conclusion, we found low pelvic osteolysis rates, acceptable overall wear
      rates, satisfactory overall survival and excellent survival rates for aseptic
      loosening of a cementless elastic monoblock socket in patients younger than 50
      years. Ongoing tribology developments and knowledge about acetabular bone
      adaptations behind acetabular implants will further lower wear and osteolysis
      rates and optimise survival rates of cementless sockets.

PMID- 20820779
TI  - Improvement of renal functions after embolization of renal AVF in a patient who
      had been on dialysis for 5 years.
AB  - Recently, ultrasound-guided percutaneous renal biopsy has been used in the
      diagnosis of renal diseases. Development of an arteriovenous fistula (AVF), which
      is one of the post-biopsy complications, is not frequently encountered. AVFs are
      usually asymptomatic; however, they may lead to serious outcomes. We report a 21
      year-old patient, who had been on dialysis for 5 years. Due to high blood
      pressure (230/160 mmHg) and a thrill in the lumbar area detected on physical
      examination, Doppler examination was performed and a renal AVF was detected.
      Because the patient had a history of renal biopsy 5 years previously, the fistula
      was thought to be secondary to the biopsy. After embolization of the AVF, renal
      functions improved enough to terminate dialysis treatment.

PMID- 20820780
TI  - Long-term safety and effectiveness of the "OptEase" vena cava filter.
AB  - PURPOSE: To assess the long-term safety and effectiveness of the OptEase inferior
      vena cava (IVC) filter. MATERIALS AND METHODS: In this Institutional Review Board
      approved, retrospective study, we reviewed data of 71 patients who received an
      OptEase filter at our institution from 2002 to 2007. Thirty-nine (55%) patients
      had symptoms of venous thromboembolism before filter placement. The indications
      for filter included contraindication to anticoagulation in 31 (44%) patients,
      prophylaxis against pulmonary embolism (PE) in 29 (41%) patients, and failure of
      anticoagulation in 11 (15%) patients. Procedure-related complications, such as
      symptomatic post-filter PE, deep venous thrombosis (DVT), IVC occlusion, and
      incidental imaging-evident filter-related complications, were recorded. Safety
      was assessed by the occurrence of filter-related complications during placement
      and follow-up. Effectiveness was assessed by the occurrence of post-filter PE.
      RESULTS: Sixty-five (92%) filters were placed under fluoroscopy, and 6 (8%) were
      placed using intravascular ultrasound guidance. Seventy (99%) filters were placed
      successfully. Seven (10%) filters were placed in the suprarenal cava. Retrieval
      was attempted in 14 (20%) patients, and 12 filters were successfully retrieved.
      Clinical follow-up was available for 20 +/- 21 months. Symptoms of postfilter PE
      and DVT occurred in 15% (n = 11) and 10% (n = 7) patients, respectively. None of
      these patients had computed tomography (CT)-proven PE, and only one had
      ultrasound-proven new DVT. One patient had symptomatic IVC occlusion. Follow-up
      abdominal CT in 20 patients showed thrombus in the filter in two of them. There
      were no instances of filter migration, filter tilt, or caval wall penetration.
      CONCLUSION: The OptEase filter appears to have an acceptable long-term safety
      profile. The filter was effective against PE.

PMID- 20820781
TI  - Superiority of transcutaneous oxygen tension measurements in predicting limb
      salvage after below-the-knee angioplasty: a prospective trial in diabetic
      patients with critical limb ischemia.
AB  - PURPOSE: To assess postprocedural angiograms, the ankle-brachial index (ABI), and
      transcutaneous oxygen tension (TcPO2) to predict outcome after infrageniculate
      angioplasty (PTA) in diabetic patients with critical limb ischemia (CLI)
      scheduled for amputation. MATERIALS AND METHODS: PTA was performed in 28 diabetic
      patients with CLI confined to infrapopliteal vessels. We recorded patency of
      crural vessels, including the vascular supply of the foot as well as the ABI and
      TcPO2 of the foot. RESULTS: Technical success rate was 92.9% (n = 26), and limb
      salvage rate at 12 months was 60.7% (n = 17). The number of patent straight
      vessels above and below the level of the malleoli increased significantly in
      patients avoiding amputation. Amputation was unnecessary in 88.2% (n = 15)
      patients when patency of at least one tibial artery was achieved. In 72.7% (n =
      8) of patients, patency of the peroneal artery alone was not sufficient for limb
      salvage. ABI was of no predictive value for limb salvage. TcPO2 values increased
      significantly only in patients not requiring amputation (P = 0.015). In patients
      with only one tibial artery supplying the foot or only a patent peroneal artery
      in postprocedural angiograms, TcPO2 was capable of reliably predicting the
      outcome. CONCLUSION: Below-the-knee PTA as an isolated part of therapy was
      effective to prevent major amputation in more than a half of diabetic patients
      with CLI. TcPO2 was a valid predictor for limb salvage, even when angiographic
      outcome criteria failed.

PMID- 20820782
TI  - Cryptotanshinone has diverse effects on cell cycle events in melanoma cell lines
      with different metastatic capacity.
AB  - PURPOSE: Cryptotanshinone is a major active component of Salvia miltiorrhiza,
      which is often used as Chinese herbal medicine in cancer therapy. Here, we
      systematically assessed the anti-tumor effect of Cryptotanshinone on two melanoma
      cell lines with low/high-metastatic capacity (B16/B16BL6). METHODS: MTT and LDH
      assays were used to evaluate cell growth and cytotoxicity. We assessed the effect
      of Cryptotanshinone on cell apoptosis or proliferation by Annexin V, TUNEL or
      BrdU assay. Cell cycle distribution was detected by flow cytometry. The integrity
      of cell cycle checkpoints was determined by mutational analyses of B-RAF and N
      RAS, and the expression of cell cycle-associated proteins by western blotting.
      RESULTS: Treatment with Cryptotanshinone had no obvious effect on cell apoptosis
      but significantly inhibited cell proliferation. Cryptotanshinone slightly
      increased the expression of p53, Chk1, and Chk2 in both B16 and B16BL6.
      Interestingly, Cryptotanshinone induced G1 arrest with a concomitant increase in
      p21 expression in B16BL6 cells. However, in B16 cells, Cryptotanshinone induced
      the G2/M arrest through its induction of Cdc25c. Regulation of Cyclin A1, Cyclin
      B1 and Cdk1/cdc2 expression might contribute to the different cell cycle patterns
      in B16 and B16BL6 after Cryptotanshinone treatment. CONCLUSIONS: Cryptotanshinone
      could have diverse effects on cell cycle events in melanoma cell lines with
      different metastatic capacity. This property might offer an opportunity to study
      underlying mechanisms for the different antitumor effects of administered
      Cryptotanshinone in B16 and B16BL6 cells.

PMID- 20820783
TI  - Joostella atrarenae sp. nov., a novel member of the Flavobacteriaceae originating
      from the black sea sand of Jeju Island.
AB  - Strain M1-2(T) was isolated from the black sand from the seashore of Jeju Island,
      Republic of Korea and was classified using a polyphasic taxonomic approach.
      Strain M1-2(T) appeared as Gram-negative, motile rods that could grow in the
      presence of 1-10% (w/v) NaCl and at temperatures ranging from 4 to 37 degrees C.
      This isolate has catalase and oxidase activity and hydrolyses aesculin, DNA and
      L: -tyrosine. Based on phylogenetic analysis using 16S rRNA gene sequences,
      strain M1-2(T) belongs to the genus Joostella and is clearly distinct from the
      other described species of this genus, Joostella marina (type strain En5(T)). The
      16S rRNA gene sequence similarity level between M1-2(T) and J. marina En5(T) is
      97.2%, and the DNA-DNA relatedness value between the two strains is 23.9%. Strain
      M1-2(T) contains MK-6 as the major menaquinone and iso-C15:0, summed feature 3
      (C16:1 omega7c and/or iso-C15:0 2OH) and iso-C17:0 3OH as major cellular fatty
      acids. The DNA G + C content is 32.3 mol%. These data suggest that strain M1-2(T)
      should be classified as a novel species, for which the name Joostella atrarenae
      sp. nov. is proposed. The type strain for the novel species is M1-2(T) (= KCTC
      23194(T) = NCAIM B.002413(T)).

PMID- 20820784
TI  - AtCML8, a calmodulin-like protein, differentially activating CaM-dependent
      enzymes in Arabidopsis thaliana.
AB  - Plants express many calmodulins (CaMs) and calmodulin-like (CML) proteins that
      sense and transduce different Ca(2+) signals. Previously, we reported divergent
      soybean (Glycine max) CaM isoforms (GmCaM4/5) with differential abilities to
      activate CaM-dependent enzymes. To elucidate biological functions of divergent
      CaM proteins, we isolated a cDNA encoding a CML protein, AtCML8, from
      Arabidopsis. AtCML8 shows highest identity with GmCaM4 at the protein sequence
      level. Expression of AtCML8 was high in roots, leaves, and flowers but low in
      stems. In addition, the expression of AtCML8 was induced by exposure to salicylic
      acid or NaCl. AtCML8 showed typical characteristics of CaM such as Ca(2+)
      dependent electrophoretic mobility shift and Ca(2+) binding ability. In
      immunoblot analyses, AtCML8 was recognized only by antiserum against GmCaM4 but
      not by GmCaM1 antibodies. Interestingly, AtCML8 was able to activate
      phosphodiesterase (PDE) but did not activate NAD kinase. These results suggest
      that AtCML8 acts as a CML protein in Arabidopsis with characteristics similar to
      soybean divergent GmCaM4 at the biochemical levels.

PMID- 20820785
TI  - Biophysical costs associated with tetrodotoxin resistance in the sodium channel
      pore of the garter snake, Thamnophis sirtalis.
AB  - Tetrodotoxin (TTX) is a potent toxin that specifically binds to voltage-gated
      sodium channels (NaV). TTX binding physically blocks the flow of sodium ions
      through NaV, thereby preventing action potential generation and propagation. TTX
      has different binding affinities for different NaV isoforms. These differences
      are imparted by amino acid substitutions in positions within, or proximal to, the
      TTX-binding site in the channel pore. These substitutions confer TTX-resistance
      to a variety of species. The garter snake Thamnophis sirtalis has evolved TTX
      resistance over the course of an arms race, allowing some populations of snakes
      to feed on tetrodotoxic newts, including Taricha granulosa. Different populations
      of the garter snake have different degrees of TTX-resistance, which is closely
      related to the number of amino acid substitutions. We tested the biophysical
      properties and ion selectivity of NaV of three garter snake populations from Bear
      Lake, Idaho; Warrenton, Oregon; and Willow Creek, California. We observed changes
      in gating properties of TTX-resistant (TTXr) NaV. In addition, ion selectivity of
      TTXr NaV was significantly different from that of TTX-sensitive NaV. These
      results suggest TTX-resistance comes at a cost to performance caused by changes
      in the biophysical properties and ion selectivity of TTXr NaV.

PMID- 20820786
TI  - Olfactory sensitivity for sperm-attractant aromatic aldehydes: a comparative
      study in human subjects and spider monkeys.
AB  - Using a three-alternative forced-choice ascending staircase procedure, we
      determined olfactory detection thresholds in 20 human subjects for seven aromatic
      aldehydes and compared them to those of four spider monkeys tested in parallel
      using an operant conditioning paradigm. With all seven odorants, both species
      detected concentrations <1 ppm, and with several odorants single individuals of
      both species even discriminated concentrations <1 ppb from the solvent. No
      generalizable species differences in olfactory sensitivity were found despite
      marked differences in neuroanatomical and genetic features. The across-odorant
      patterns of sensitivity correlated significantly between humans and spider
      monkeys, and both species were more sensitive to bourgeonal than to lilial,
      cyclamal, canthoxal, helional, lyral, and 3-phenylpropanal. No significant
      correlation between presence/absence of an oxygen-containing moiety attached to
      the benzene ring or presence/absence of an additional alkyl group next to the
      functional aldehyde group, and olfactory sensitivity was found in any of the
      species. However, the presence of a tertiary butyl group in para position
      (relative to the functional aldehyde group) combined with a lack of an additional
      alkyl group next to the functional aldehyde group may be responsible for the
      finding that both species were most sensitive to bourgeonal.

PMID- 20820787
TI  - Antennae in the hawkmoth Manduca sexta (Lepidoptera, Sphingidae) mediate
      abdominal flexion in response to mechanical stimuli.
AB  - Flying insects rely on the integration of feedback signals from multiple sensory
      modalities. Thus, in addition to the visual input, mechanosensory information
      from antennae is crucial for stable flight in the hawkmoth Manduca sexta.
      However, the nature of compensatory reflexes mediated by mechanoreceptors on the
      antennae is unknown. In this study we describe an abdominal flexion response
      mediated by the antennal mechanosensory input during mechanical body rotations.
      Such reflexive abdominal motions lead to shifts in the animal's center of mass,
      and therefore changes in flight trajectory. Moths respond with abdominal flexion
      both to visual and mechanical rotations, but the mechanical response depends on
      the presence of the mass of the flagellum. In addition, the mechanically mediated
      flexion response is about 200 degrees  out of phase with the visual response and
      adds linearly to it. Phase-shifting feedback signals in such a manner can lead to
      a more stable behavioral output response when the animal is faced with turbulent
      perturbations to the flight path.

PMID- 20820788
TI  - Vision as a third sensory modality to elicit attack behavior in a nocturnal
      spider.
AB  - Cupiennius salei (Ctenidae) has been extensively studied for many years and is
      probably the only spider that presently can be considered a model organism for
      neuro-ethology. The night-active spiders have been shown to predominantly rely on
      their excellent mechano-sensory systems for courtship and prey capture, whereas
      vision was assumed to play a minor role, if any, in these behavioral contexts.
      Using slowly moving discs presented on a computer screen it could be shown for
      the first time that visual stimuli alone can elicit attack behavior (abrupt
      approaching reactions) in these spiders as well. These observations suggest that
      visual information could be used by the spiders to elicit and guide predatory
      behavior. Attack behavior in Cupiennius salei can thus be triggered independently
      by three sensory modalities--substrate vibrations, airflow stimuli, and visual
      cues--and offers an interesting model system to study the interactions of
      multimodal sensory channels in complex behavior.

PMID- 20820789
TI  - Comparative outcomes in intestinal atresia: a clinical outcome and
      pathophysiology analysis.
AB  - OBJECTIVE: To describe the outcomes of 130 intestinal atresias between 1982 and
      2007. METHODS: Records were analyzed for location, demographics, prenatal
      diagnosis, birth weight, associated anomalies, surgery, establishment of oral
      intake, re-interventions and mortality. Statistical analyses were performed using
      Fisher test and ANOVA. RESULTS: There were 59 duodenal (30 male), 63 jejuno-ileal
      (34 male) and 8 colonic atresias (3 male). Prenatal diagnosis was established in
      27 (46%) duodenal (DA), 26 (41%) jejuno-ileal (JIA) and 1 (12.5%) colonic
      atresias (CA). The mean birth weights, 2,380.5 g (SD 988) DA, 2,814 g (SD 755)
      JIA and 3,153 g (SD 527) CA were significantly different (p = 0.011). The mean
      gestational ages were 36, 37 and 37 weeks in DA, JIA and CA, respectively (p-NS).
      Associated congenital anomalies were seen in 41 (76%) DA, 32 (52%) JIA and 3
      (38%) CA (p = 0.08, NS). The median time to full oral feeds after surgery was 18
      days in DA, 20 days in JIA and 15.6 days in CA, respectively (p > 0.05). Eight
      patients with DA and nine patients with JIA underwent repeat surgery for adhesive
      obstruction. Adhesive bowel obstruction was most common in the first year after
      surgery in both groups (15/17). Gastroschisis was seen in six (10%) of JIA and
      three (35%) of CA. Two patients in the JIA group underwent bowel lengthening.
      Patients with gastroschisis and those with associated anomalies needed prolonged
      duration of TPN after JIA correction. There was no mortality in the duodenal
      atresia and colonic atresia groups. Six patients in the JIA group died, three of
      severe atresias coupled with multiple anomalies and three of cholestasis and
      sepsis. CONCLUSION: Distal atresias are difficult to diagnose antenatally.
      Proximal atresias have a significantly lower birth weight than distal atresias.
      Associated anomaly screening is important in all atresias.

PMID- 20820790
TI  - Bladder injuries following inguinal canal surgery in infants.
AB  - PURPOSE: Surgery of the inguinal canal is very common in infancy. Occasionally,
      injury of the bladder may occur with severe consequences. The aim of this paper
      was to warn young surgeons of this serious complication. METHODS: During the last
      2 years, we observed four cases of bladder injury following surgery on inguinal
      canal. All were males. The indication for surgery was inguinal hernia in three
      patients and cryptorchidism in one patient. RESULTS: Two cases presented with
      urinary peritonitis. One child was referred later for a retracted bladder with
      reflux. In one child, the lesion was promptly recognized and repaired. Of the
      four cases, two ruptures of the bladder caused transient sequaele, i.e.
      persisting catheter drainage, and voiding disorders later. In two cases, there
      were serious consequences: the bladder had to be partially removed in one child,
      ending up in temporary ureterostomy and subsequent reconstruction with bladder
      augmentation. The fourth child developed a small, water clock-shaped bladder with
      a thick wedge of scarred tissue, and bilateral ureteral reimplantation with
      bladder augmentation was necessary. CONCLUSIONS: Surgery of the inguinal canal is
      very common in children and infants, and is often performed by trainees.
      Awareness of this serious event should be emphasized in training programs.

PMID- 20820791
TI  - Effect of a vegetable-oil emulsion on body composition; a 12-week study in
      overweight women on a meal replacement therapy after an initial weight loss: a
      randomized controlled trial.
AB  - PURPOSE: The maintenance of an obtained lower weight level is often found to be
      difficult. The aim of this study was to determine weight maintenance after an
      initial weight loss by consumption of a meal replacement with a vegetable-oil
      emulsion associated with prolonged satiety. METHODS: After a 6-week weight loss
      period with very low calorie diet (VLCD), subjects with >5% body weight (BW) loss
      were randomized to a 12-week weight maintenance follow-up period, comparing a
      partial meal replacement diet containing a vegetable-oil emulsion (test) or dairy
      fat (control). Anthropometric data and safety variables were collected at
      baseline and after 4, 8 and 12 weeks. RESULTS: A significant weight loss was
      observed during the 12-week weight maintenance diet in the test and control
      group, respectively; 1.0 +/- 2.1 kg (p < 0.05) versus 1.3 +/- 2.1 kg (p < 0.05)
      with no significant difference between the groups. Body fat mass (BFM) decreased
      significantly (p < 0.05) in the test group (--1.7%) compared to the control group
      (--0.8%). CONCLUSIONS: Addition of a vegetable-oil emulsion to a meal replacement
      weight maintenance program after an initial weight loss using VLCD was associated
      with decreased BFM by 0.9% without any change in BW between the two groups.

PMID- 20820792
TI  - Retrograde dynamic locked nailing for aseptic nonunion of femoral supracondyle
      after antegrade locked nailing.
AB  - INTRODUCTION: Using antegrade exchange locked nailing to treat femoral
      supracondylar aseptic nonunion may sometimes have some limitations. Using
      retrograde locked nailing to treat such situations may achieve great advantages.
      The feasibility of such a technique was investigated. MATERIALS AND METHODS:
      Fifteen consecutive adult patients were treated. Indications for this technique
      were an aseptic nonunion of the femoral supracondyle, an antegradely inserted
      locked nail, shortening of the femur less than 1.5 cm, and a dilapidated cortex
      of the distal fragment unsuitable for performing antegrade exchange locked
      nailing. The technique included the closed removal of all previous implants,
      insertion of a retrograde dynamic locked nail, cancellous bone grafting from the
      lateral tibial condyle, and with or without plate augmentation. Early ambulation
      with protected weight bearing was allowed postoperatively, and knee range of
      motion exercise was encouraged. RESULTS: Thirteen patients were followed up for a
      median of 2.5 years (range 1.1-4.5 years). All fractures were healed with a
      median union period of 4.5 months (range 3.5-5.5 months). There were no wound
      infections, nonunions or malunions. The knee function satisfactorily improved
      from none to 11 out of 13 patients (p < 0.001). CONCLUSION: Retrograde dynamic
      locked nailing is an excellent alternative treatment for the treatment of aseptic
      nonunions of femoral supracondyles after antegrade locked nailing. However, this
      technique may only be used when antegrade exchange locked nailing is unsuitable
      for use. The technique is not complex and its success rate is high.

PMID- 20820793
TI  - Localized gray matter volume abnormalities in generalized anxiety disorder.
AB  - Generalized anxiety disorder (GAD) is characterized by excessive and persistent
      worrying. Neural substrates of this disorder are insufficiently understood, which
      relates to functional as well as to structural brain abnormalities. Especially,
      findings on the neuroanatomy of GAD have been inconsistent and were predominantly
      derived from pediatric samples. Therefore, we studied adult patients. Thirty-one
      women (16 patients with GAD and 15 healthy control participants) underwent
      structural MRI scanning. Gray matter volumes for specific brain regions involved
      in worrying, anticipatory anxiety, and emotion regulation were analyzed by means
      of voxel-based morphometry. Relative to controls, patients with GAD had larger
      volumes of the amygdala and the dorsomedial prefrontal cortex (DMPFC). Moreover,
      patients' self-reports on symptom severity were positively correlated with
      volumes of the DMPFC and the anterior cingulate cortex. Patients with GAD show
      localized gray matter volume differences in brain regions associated with
      anticipatory anxiety and emotion regulation. This abnormality may represent
      either a predisposition for GAD or a consequence of disorder-specific behavior,
      such as chronic worrying. This issue should be addressed in future MRI studies.

PMID- 20820794
TI  - Olfactory identification and preference in bipolar disorder and schizophrenia.
AB  - Olfactory identification deficit appears to be an enduring feature of
      schizophrenia, but it is unclear whether it is specific to schizophrenia or
      present in psychotic disorders in general. The aim of the present study was to
      compare olfactory identification and olfactory preference in schizophrenia and
      bipolar disorder. Individuals with schizophrenia or bipolar disorder and
      demographically matched healthy participants were given the University of
      Pennsylvania Smell Identification Test (UPSIT) to assess olfactory identification
      ability. To examine olfactory hedonic judgment, participants were also asked to
      indicate their preference for each UPSIT item on a 5-point rating scale,
      immediately after odor identification. Clinical symptoms and social competence
      were also assessed. Both schizophrenic and bipolar groups showed olfactory
      identification deficits compared with the healthy controls, but schizophrenic
      patients were more impaired than bipolar patients on the UPSIT accuracy.
      Interestingly, both bipolar and schizophrenic patients rated odors to be more
      pleasant than did healthy controls, but all groups preferred odors that they
      could correctly identify to unidentified smells. Restricted range of preference
      ratings was associated with the severity of negative symptoms in schizophrenia,
      and with mania in bipolar disorder. Social competence was associated with better
      olfactory identification performance. These findings suggest that olfactory
      identification and preference are compromised in bipolar disorder as well as in
      schizophrenia, but the precise nature of these abnormalities needs to be further
      elucidated.

PMID- 20820795
TI  - Metabolic parameters in the short- and long-term treatment of schizophrenia with
      sertindole or risperidone.
AB  - The presence of the metabolic syndrome is an important risk factor for
      cardiovascular disease and diabetes. The short- and long-term metabolic safety of
      sertindole was compared to that of risperidone in a subset of patients enrolled
      in the sertindole cohort prospective (SCoP) study, an open randomized study. In
      261 randomized patients, there were moderate increases in mean weight, BMI, and
      waist circumference during treatment with either sertindole or risperidone; after
      12 weeks, the increase in weight was 1.3 and 1.1 kg, respectively, and after 36
      weeks, it was 2.2 and 2.0 kg, respectively. From baseline to last assessment (up
      to 60 weeks), weight gains of 1.8 and 1.7 kg for sertindole and risperidone,
      respectively, were observed. Similar proportions of patients (sertindole: 17%
      versus risperidone: 16%) had weight increases >=7% from baseline to last
      assessment. The mean changes from baseline in triglycerides, total cholesterol,
      HDL-cholesterol, LDL-cholesterol, plasma glucose and blood pressure were small
      and not clinically relevant in both treatment groups. No patient in either of the
      groups developed type 2 diabetes during the study. At last assessment, the
      prevalence of metabolic syndrome (International Diabetes Federation) was 17% in
      the sertindole group and 26% in the risperidone group and the incidence of
      metabolic syndrome was 7% in the sertindole group and 10% in the risperidone
      group. Treatment with either sertindole or risperidone did not appear to be
      associated with an increased comparative risk of developing metabolic syndrome.
      In general, the metabolic effects of sertindole and risperidone were similar.

PMID- 20820796
TI  - Restless legs syndrome as a possible predictor for psychiatric disorders in
      parents of children with ADHD.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a common disorder with
      estimated prevalence of 5% in children and 3.4% in adults. Psychiatric disorders
      are a frequent concomitant feature. Restless legs syndrome (RLS) may mimic the
      symptoms of ADHD. The aim of the study is to evaluate whether the presence of RLS
      predicts occurrence of psychiatric disorders in parents of children with ADHD.
      Thirty-seven parents of 26 children with ADHD were examined for RLS and for
      lifetime prevalence rates of psychiatric disorders and personality disorders
      based on the Structured Clinical Interview for DSM-IV Diagnoses (SCID).
      Prevalence rates in parents were 29.7% for RLS, 67.6% for Axis I and 40.5% for
      Axis II disorders. Mothers revealed higher rates for depression, anxiety
      disorders and ADHD than fathers, whereas personality disorders occurred at higher
      rates in fathers. The presence of RLS predicted a diagnosis of ADHD (odds ratio
      (OR) 21.9), agoraphobia (OR = 20.4) and any anxiety disorder (OR = 8.5). Although
      limited by the small sample size, we found evidence for increased rates of
      cluster B personality disorders (OR = 59.3) in parents with RLS. All parents of
      the latter group (100%) reported a positive family history of psychiatric
      disorders which was not the case in parents without RLS (69.2%) excluding the
      index children with ADHD. RLS seems to indicate increased vulnerability for
      psychiatric disorders, i.e., ADHD and anxiety disorders, in a subgroup of parents
      from ADHD children. Synaptic dysfunction affecting dopaminergic transmission
      among other transmitter systems may be a common final pathway related to the
      phenotypic spectrum of ADHD.

PMID- 20820797
TI  - Charles Foix (1882-1927).

PMID- 20820798
TI  - Autonomic dysfunction in non-paraneoplastic sensory neuronopathy: beyond sensory
      abnormalities.
AB  - Sensory neuronopathies (SN) represent a subgroup of peripheral nervous system
      disorders which are becoming increasingly recognized. Despite a few reports of
      autonomic dysfunction, this complication has not been fully appreciated.
      Autonomic function was quantified through tests of sympathetic and
      parasympathetic function (forming the Autonomic Tests Score, ATS), and through a
      40-item questionnaire assessing autonomic symptoms (constituting the Autonomic
      Questionnaire Score, AQS). Twenty patients were enrolled. Forty-six age- and
      gender-matched controls were evaluated for the AQS and 15 for the ATS. All
      patients reported symptoms of autonomic dysfunction. Of the patients, 60% had one
      or more abnormal cardiovagal test, 60% orthostatic hypotension and 20% abnormal
      pupillary function. Their ATS was significantly different from the controls (p <
      0.0001). Neither the ATS nor AQS were different between groups of SN associated
      disorders. Autonomic dysfunction is a frequent and important complication in SN,
      and it does not seem to be related to a specific etiology, as previously thought.

PMID- 20820799
TI  - FDG-PET SUV can distinguish between spinal sarcoidosis and myelopathy with canal
      stenosis.
AB  - Spinal cord sarcoidosis is a rare manifestation of sarcoidosis. Magnetic
      resonance imaging (MRI) of spinal cord sarcoidosis sometimes resembles that of
      the non-inflammatory spinal cord lesion. (18)F-fluorodeoxyglucose positron
      emission tomography (FDG-PET) is an effective method to detect both systemic and
      central nervous system lesions in sarcoidosis. This study compared the standard
      uptake value (SUV) of FDG-PET between spinal cord sarcoidosis and non
      inflammatory spinal cord lesions. We retrospectively reviewed the records of
      patients who underwent both spinal MRI and FDG-PET scans. We used SUV to evaluate
      the FDG-PET uptake of the lesion. The region of interest was the center of high
      intensity areas on T2-weighted MR images. We included three patients with spinal
      cord sarcoidosis, five with myelomalacia caused by cervical spondylosis or
      ossification of the posterior longitudinal ligament, one with spinal cord edema
      associated with cervical spondylosis, and one with spinal cord edema associated
      with dural arteriovenous fistula. The spinal cord sarcoidosis group had a
      significantly higher SUV (mean 4.38, range 3.30-4.93) than patients with the
      other diseases (mean 1.87, range 1.42-2.74). The SUV of FDG-PET thus may be able
      to distinguish spinal cord sarcoidosis from other non-inflammatory lesions. FDG
      PET can play an important role in the diagnosis of spinal cord sarcoidosis
      because the gadolinium enhancement in MRI is sometimes seen in spondylotic
      myelopathy or vascular malformation. FDG-PET is informative for the accurate
      diagnosis of spinal cord sarcoidosis and may enable clinicians to start treatment
      at an earlier stage.

PMID- 20820800
TI  - Gamma-aminobutyric acid (GABA) receptor rho (GABRR) polymorphisms and risk for
      essential tremor.
AB  - Some clinical and experimental data suggest a possible role of gamma
      aminobutyrate (GABA)-ergic mechanisms in the pathophysiology of essential tremor
      (ET), such as the improvement of ET with some GABAergic drugs and the development
      of an experimental model of ET in GABA A receptor alpha-1 knockout mice (postural
      and kinetic tremor and motor incoordination similar to human ET). To investigate
      the possible association between the GABA receptor subtype rho1, rho2, and rho3
      (GABRR1, GABRR2, and GABRR3) genotypes and allelic variants of the single
      nucleotide polymorphisms GABRR1-M26V (Met26Val, rs12200969), GABRR1-H27R
      (His26Arg, rs1186902), GABRR2-T455M (Thr55Met, rs282129), and GABRR3-Y205X
      (Tyr205X, rs832032), and the risk for ET, we studied the frequency of the
      previously mentioned GABRR genotypes and allelic variants in 200 patients with ET
      and 250 healthy controls using TaqMan genotyping. The frequencies of the GABBR1
      genotypes and allelic variants of the studied polymorphisms did not differ
      significantly between patients with ET and controls, and were unrelated with the
      age at onset of tremor, gender, localization of tremor, and response of tremor to
      ethanol. These data suggest that the single nucleotide polymorphisms studied in
      the GABBR genes are not related to the risk for ET.

PMID- 20820802
TI  - Proteome analysis of Arabidopsis seedlings exposed to bacterial volatiles.
AB  - Plant root-associated bacteria (rhizobacteria) elicit plant basal immunity
      referred to as induced systemic resistance (ISR) against multiple pathogens.
      Among multi-bacterial determinants involving such ISR, the induction of ISR and
      promotion of growth by bacterial volatile compounds was previously reported. To
      exploit global de novo expression of plant proteins by bacterial volatiles,
      proteomic analysis was performed after exposure of Arabidopsis plants to the
      rhizobacterium Bacillus subtilis GB03. Ethylene biosynthesis enzymes were
      significantly up-regulated. Analysis by quantitative reverse transcriptase
      polymerase chain reaction confirmed that ethylene biosynthesis-related genes SAM
      2, ACS4, ACS12, and ACO2 as well as ethylene response genes, ERF1, GST2, and CHIB
      were up-regulated by the exposure to bacterial volatiles. More interestingly, the
      emission of bacterial volatiles significantly up-regulated both key defense
      mechanisms mediated by jasmonic acid and salicylic acid signaling pathways. In
      addition, high accumulation of antioxidant proteins also provided evidence of
      decreased sensitivity to reactive oxygen species during the elicitation of ISR by
      bacterial volatiles. The present results suggest that the proteomic analysis of
      plant defense responses in bacterial volatile-mediated ISR can reveal the
      mechanisms of plant basal defenses orchestrated by endogenous ethylene production
      pathways and the generation of reactive oxygen species.

PMID- 20820803
TI  - Survival prognostic factors and clinical outcomes in patients with spinal
      metastases.
AB  - PURPOSE: In patients with metastatic disease to the spine, patient selection for
      surgery and the extent of surgery to perform thereafter remains controversial,
      with the patient's survival prognosis the most important consideration. For this
      reason, we conducted a prospective study investigating prognostic factors and
      clinical outcomes in a consecutive series of patients with vertebral metastases.
      METHODS: A total of 142 consecutive patients with vertebral metastases referred
      to us for consideration of surgery were prospectively enrolled into this study.
      Of these, 118 patients subsequently underwent palliative surgery for intractable
      pain or radiculopathy, bony instability or spinal cord compression. Patients were
      followed up for 12 months or until death. A multivariate analysis of the patients
      was conducted using the Cox proportional hazards model. The survival predictive
      accuracy of the Tokuhashi score was also investigated. For the patients who
      underwent surgery, pre- and post-operative outcomes were assessed on pain,
      neurological deficit, function and overall quality of life. RESULTS: The overall
      12-month mortality rate was 50.7% and the median survival was 5 months.
      Multivariate analysis showed that independent prognostic factors for survival
      after spinal metastases include primary tumour type, Karnofsky functional status,
      ASA score and pain. Neither the original nor revised Tokuhashi scores were
      reliable in predicting survival in our European population. In the patients who
      underwent operative intervention, there was an immediate and prolonged
      improvement in pain, neurological deficit, function and quality of life in the
      majority of cases. CONCLUSIONS: The potential for rapid and maintained
      improvement in clinical outcome and quality of life should be considered when
      selecting patients with metastatic disease to the spine for surgery rather than
      basing decisions solely on survival prognostic factors comprising current scoring
      systems.

PMID- 20820804
TI  - Comprehensive geriatric assessment in Korean elderly cancer patients receiving
      chemotherapy.
AB  - BACKGROUND: Growing evidence suggests that a comprehensive geriatric assessment
      (CGA) in older patients with cancer can detect unsuspected health problems,
      predict survival, and predict tolerance to chemotherapy. However, studies
      regarding CGA in cancer patients are scarce in Asia. METHODS: We prospectively
      enrolled 65 elderly cancer patients who were candidates of systemic chemotherapy
      between July 2006 and March 2008. Baseline CGA data including demographic
      information, comorbidity, functional status by means of Activities of Daily
      Living (ADL), and Instrumental Activities of Daily Living (IADL), cognition,
      psychological state, nutritional status, and medication were collected and
      analyzed. Quality of life (QoL) was assessed by the EORTC questionnaire QLQ-C30.
      RESULTS: Of the 65 patients, the median age was 71 years (range, 65-80), 49 (75%)
      were males, and 58 (89%) had Eastern Cooperative Oncology Group performance
      status (ECOG PS) 0 or 1. All patients had solid tumor, 74% received palliative
      chemotherapy, and 18% received adjuvant chemotherapy. Twenty-five percent of
      patients had Charlson's comorbidity index score of 2 or more, 23% were ADL
      dependent, and 14% were IADL dependent. Using Mini-Mental Status Exam (MMSE), it
      was found that 51% of patients had mild cognitive impairment (MMSE score 17-24),
      and 5% had cognitive impairment (<= 16). Forty percent of patients had depression
      by Short form Geriatric Depression Scale (SGDS), 19% had malnutrition by Mini
      Nutritional Assessment (MNA), and 23% had body mass index (BMI) less than 19.4
      kg/m(2) (lowest 10%). Global health status/quality of life (QoL) was less than
      50% in 39% of patients. Frail patients according to the Balducci classification
      had significantly poor ECOG PS and worse global health status/QoL. CONCLUSION:
      CGA was feasible and could detect multiple unsuspected health problems including
      functional impairment and malnutrition in Korean elderly cancer patients
      receiving chemotherapy.

PMID- 20820805
TI  - Horses naturally infected by Trypanosoma vivax in southern Brazil.
AB  - In this study, we reported the first outbreak of the infection by Trypanosoma
      vivax in horses in southern Brazil, a non-endemic region where bovines have only
      recently been found infected by this trypanosome species. We evaluated 12 horses
      from a farm in southern Brazil, where four horses displayed pale mucous
      membranes, fever, weight loss, and swelling of abdomen, prepuce, or vulva. The
      diagnosis of T. vivax was confirmed in four horses by morphological parameters of
      trypomastigotes in blood smears and species-specific PCR. All T. vivax-infected
      animals showed anemia, and most showed increased levels of beta-1, beta-2, and
      gamma globulins. Horses were treated with diminazene aceturate, but cure was not
      achieved, and the disease relapsed after therapy. These findings demonstrated
      that Brazilian T. vivax isolates, which were already reported infecting cattle,
      buffaloes, goats, and sheep, can be highly pathogenic for horses, causing severe
      disease and even death of the animals due to the recurrence of the infection.

PMID- 20820806
TI  - 1,3-Propandiol production by engineered Hansenula polymorpha expressing dha genes
      from Klebsiella pneumoniae.
AB  - Currently, 1,3-propanediol (1,3-PD) is an important chemical widely used in
      polymer production, but its availability is being restricted owing to its
      expensive chemical synthesis. A methylotrophic yeast Hansenula polymorpha was
      engineered by expression of dhaB1, dhaB2, dhaB3, dhaB(RA1) and dhaB(RA2) encoding
      glycerol dehydratase complex and dhaT encoding 1,3-PD oxidoreductase from
      Klebsiella pneumoniae under direction of promoter of glyceraldehyde-3 phosphate
      dehydrogenase (GAPDH). The engineered recombinant yeast strain can produce 1,3-PD
      from glucose (2.4 g L(-1)) as well as glycerol (0.8 g L(-1)), which might lead to
      a safe and cost-effective method for industrial production of 1,3-PD from various
      biomass resources.

PMID- 20820807
TI  - Posterior cricoid region fluoroscopic findings: the posterior cricoid plication.
AB  - The region posterior to the cricoid cartilage is challenging to assess
      fluoroscopically. The purpose of this investigation is to critically evaluate the
      posterior cricoid (PC) region on fluoroscopy and describe patterns of common
      findings. This was a case control study. All fluoroscopic swallowing studies
      performed between June 16, 2009, and February 9, 2010, were reviewed for features
      seen in the PC region. These findings were categorized into distinct patterns and
      compared to fluoroscopic studies performed in a cohort of normal volunteers. Two
      hundred patient studies and 149 healthy volunteer studies were reviewed. The mean
      age of the referred patient cohort and the volunteer cohort was 57 years (+/-19)
      and 61 years (+/-16), respectively (p > 0.05). The patient cohort was 53% male
      and the control cohort was 56% female (p > 0.05). Four groups were identified.
      Pharyngoesophageal webs were seen in 7% (10/149) of controls and 14% (28/200) of
      patients (p = 0.03). A PC arch impression was seen in 16% of patients (32/200)
      and controls (24/149) (p = 1). A PC plication was demonstrated in 23% (34/149) of
      controls and 30% (60/200) of patients (p = 0.13). No distinctive PC region
      findings were seen in 54% (81/149) of controls and 42% (84/200) of referred
      patients (p = 0.02). Four patients (2%) had both a web and a PC plication. Four
      categories of PC region findings were identified (unremarkable PC region, web, PC
      arch impression, and PC plication). Both patients referred for swallowing studies
      and healthy volunteers demonstrated esophageal webs, PC arch impressions, and PC
      plications. Only webs were more common in patients than in control subjects (p =
      0.03). The PC impression and PC plication are likely to represent normal variants
      that may be identified on fluoroscopic swallow studies.

PMID- 20820808
TI  - Videofluorographic evaluation of mastication and swallowing of Japanese udon
      noodles and white rice.
AB  - A videofluorographic (VF) swallowing study was performed on 22 healthy volunteers
      to observe the complete mastication and swallowing phases for Japanese udon
      noodles and white rice. The hardness, stickiness, and cohesiveness of food
      samples were measured using a food texture analyzing system. VF images were
      acquired using a versatile fluoroscopic unit and barium sulfate was used as a
      contrast medium. Udon noodles had a harder and smoother food texture than white
      rice. Fewer chewing movements and more stage 2 transport were seen during the
      consumption of udon noodles than for white rice.

PMID- 20820810
TI  - Who should decide the best minimally invasive approach? Should we listen to our
      patients?

PMID- 20820811
TI  - Stent placement provides safe esophageal closure in thoracic NOTES(TM)
      procedures.
AB  - BACKGROUND: Safe esophageal closure remains a challenge in transesophageal
      Natural Orifice Transluminal Endoscopic Surgery (NOTES). Previously described
      methods, such as suturing devices, clips, or submucosal tunneling, all have
      weaknesses. In this survival animal series, we demonstrate safe esophageal
      closure with a prototype retrievable, antimigration stent. METHODS: Nine
      Yorkshire swine underwent thoracic NOTES procedures. A double-channel gastroscope
      equipped with a mucosectomy device was used to create an esophageal mucosal
      defect. A 5-cm submucosal tunnel was created and the muscular esophageal wall was
      incised with a needle-knife. Mediastinoscopy and thoracoscopy were performed in
      all swine; lymphadenectomy was performed in seven swine. A prototype small
      intestinal submucosal (SurgiSIS((r))) covered stent was deployed over the
      mucosectomy site and tunnel. Three versions of the prototype stent were
      developed. Prenecropsy endoscopy confirmed stent location and permitted stent
      retrieval. Explanted esophagi were sent to pathology. RESULTS: Esophageal
      stenting was successful in all animals. Stent placement took 15.8 +/- 4.8 minuted
      and no stent migration occurred. Prenecropsy endoscopy revealed proximal ingrowth
      of esophageal mucosa and erosion with Stent A. Mucosal inflammation and erosion
      was observed proximally with Stent B. No esophageal erosion or pressure damage
      from proximal radial forces was seen with Stent C. On necropsy, swine 5 had a 0.5
      cm periesophageal abscess. Histology revealed a localized inflammatory lesion at
      the esophageal exit site in swine 1, 3, and 9. The mucosectomy site was partially
      healed in three swine and poorly healed in six. All swine thrived clinically,
      except for a brief period of mild lethargy in swine 9 who improved with short
      term antibiotic therapy. The submucosal tunnels were completely healed and no
      esophageal bleeding or stricture formation was observed. All swine survived 13.8
      +/- 0.4 days and gained weight in the postoperative period. CONCLUSIONS:
      Esophageal stenting provides safe closure for NOTES thoracic procedures but may
      impede healing of the mucosectomy site.

PMID- 20820812
TI  - How well does the MESTT correlate with CTCAE scale for the grading of
      dermatological toxicities associated with oral tyrosine kinase inhibitors?
AB  - BACKGROUND: Dermatological toxicities associated with tyrosine kinase inhibitors
      (TKIs) are commonly graded using the National Cancer Institute Common Terminology
      Criteria for Adverse Events (NCI-CTCAE). A new tool has been proposed by the
      Multinational Association for Supportive Care in Cancer (MASCC), namely the MASCC
      EGFRI Skin Toxicity Tool (MESTT), as a class-specific grading system. This study
      was designed to assess the correlation between the severity grading of the
      dermatological toxicities associated with TKIs using the NCI-CTCAE v4.0 and the
      MESTT. PATIENT AND METHODS: One hundred patients were interviewed at the National
      Cancer Centre Singapore with the criteria of being on erlotinib, gefitinib,
      lapatinib, sorafenib, or sunitinib over 2 weeks and manifested dermatological
      toxicities. Dermatological toxicities were graded using CTCAE and MESTT 1,
      respectively, by a single observer. Spearman's correlation test was performed on
      the results. RESULTS: Sixty-five patients (65%) experienced papulopustular rash,
      72 patients (72%) had pruritus, 85 patients (85%) had xerosis, 33 patients (33%)
      experienced nail changes, and 24 patients (24%) had alopecia. There was
      significant positive correlation between the two grading systems for all
      investigated dermatological toxicities, namely rash (r = 0.734), pruritus (r =
      0.917), xerosis (r = 0.635), and paronychia (r = 0.611) at 99% confidence level.
      CONCLUSION: Good correlation was observed between the scales, but there is a
      tendency for the MESTT tended to report higher toxicity grades for rash, xerosis,
      and paronychia. The MESTT was also found to be more useful to grade rash specific
      to TKIs and had similar usefulness for grading other studied toxicities.

PMID- 20820813
TI  - A prospective longitudinal study of chemotherapy-induced cognitive changes in
      breast cancer patients.
AB  - PURPOSE: Evidence for chemotherapy-induced cognitive impairment remains
      inconclusive. This study was designed to determine the trajectory of cognitive
      function over time in women with breast cancer, who received doxorubicin and
      cyclophosphamide (AC) alone or followed by a taxane. Associations between changes
      in cognitive function and potential covariates including anxiety, depression,
      fatigue, hemoglobin level, menopausal status, and perception of cognitive
      function were evaluated. METHODS: The Repeatable Battery for the Assessment of
      Neuropsychological Status, Stroop Test, and Grooved Pegboard were used to assess
      cognitive function in a group of 71 women prior to chemotherapy, a week after
      completing the last cycle of AC, as well as 1 week and 6 months after the
      completion of all chemotherapy. RESULTS: Cognitive impairment was found in 23% of
      women prior to chemotherapy. Hierarchical linear modeling showed significant
      decreases after receiving chemotherapy followed by improvements 6 months after
      the completion of chemotherapy in the cognitive domains of visuospatial skill (p
      < 0.001), attention (p = 0.022), delayed memory (p = 0.006), and motor function
      (p = 0.043). In contrast, immediate memory, language, and executive function
      scores did not change over time. CONCLUSION: These results suggest that having a
      breast cancer diagnosis may be associated with cognitive impairment. While
      chemotherapy may have a negative impact on cognitive function, chemotherapy
      related impairments appear to be more acute than chronic side effects of therapy.
      Further studies are needed to provide insight into the clinical significance and
      potential mechanisms of cancer and treatment-related cognitive impairments.

PMID- 20820814
TI  - How do non-physician clinicians respond to advanced cancer patients' negative
      expressions of emotions?
AB  - PURPOSE: Patients with advanced cancer often experience negative emotion;
      clinicians' empathic responses can alleviate patient distress. Much is known
      about how physicians respond to patient emotion; less is known about non
      physician clinicians. Given that oncology care is increasingly provided by an
      interdisciplinary team, it is important to know more about how patients with
      advanced cancer express emotions to non-physician clinicians (NPCs) and how NPCs
      respond to those empathic opportunities. METHOD: We audio recorded conversations
      between non-physician clinicians and patients with advanced cancer. We analyzed
      45 conversations between patients and oncology physician assistants, nurse
      practitioners, and nurse clinicians in which patients or their loved ones
      expressed at least one negative emotion to the NPC (i.e., an empathic
      opportunity). Empathic opportunities were coded three ways: type of emotion
      (anger, sadness, or fear), severity of emotion (least, moderate, or most severe),
      and NPC response to emotion (not empathic, on-topic medical response, and
      empathic response). RESULTS: We identified 103 empathic opportunities presented
      to 25 different NPCs during 45 visits. Approximately half of the empathic
      opportunities contained anger (53%), followed by sadness (25%) and fear (21%).
      The majority of emotions expressed were moderately severe (73%), followed by most
      severe (16%), and least severe (12%). The severity of emotions presented was not
      found to be statistically different between types of NPCs. NPCs responded to
      empathic opportunities with empathic statements 30% of the time. Additionally,
      40% of the time, NPCs responded to empathic opportunities with on-topic, medical
      explanations and 30% of the responses were not empathic. CONCLUSION: Patients
      expressed emotional concerns to NPCs typically in the form of anger; most
      emotions were moderately severe, with no statistical differences among types of
      NPC. On average, NPCs responded to patient emotion with empathic language only
      30% of the time. A better understanding of NPC-patient interactions can
      contribute to improved communication training for NPCs and, ultimately, to higher
      quality patient care in cancer.

PMID- 20820815
TI  - Prediction of outcome in cancer patients with febrile neutropenia: a prospective
      validation of the Multinational Association for Supportive Care in Cancer risk
      index in a Chinese population and comparison with the Talcott model and
      artificial neural network.
AB  - PURPOSE: We aimed to validate the Multinational Association for Supportive Care
      in Cancer (MASCC) risk index, and compare it with the Talcott model and
      artificial neural network (ANN) in predicting the outcome of febrile neutropenia
      in a Chinese population. METHODS: We prospectively enrolled adult cancer patients
      who developed febrile neutropenia after chemotherapy and risk classified them
      according to MASCC score and Talcott model. ANN models were constructed and
      temporally validated in prospectively collected cohorts. RESULTS: From October
      2005 to February 2008, 227 consecutive patients were enrolled. Serious medical
      complications occurred in 22% of patients and 4% died. The positive predictive
      value of low risk prediction was 86% (95% CI = 81-90%) for MASCC score >= 21, 84%
      (79-89%) for Talcott model, and 85% (78-93%) for the best ANN model. The
      sensitivity, specificity, negative predictive value, and misclassification rate
      were 81%, 60%, 52%, and 24%, respectively, for MASCC score >= 21; and 50%, 72%,
      33%, and 44%, respectively, for Talcott model; and 84%, 60%, 58%, and 22%,
      respectively, for ANN model. The area under the receiver-operating characteristic
      curve was 0.808 (95% CI = 0.717-0.899) for MASCC, 0.573 (0.455-0.691) for
      Talcott, and 0.737 (0.633-0.841) for ANN model. In the low risk group identified
      by MASCC score >= 21 (70% of all patients), 12.5% developed complications and
      1.9% died, compared with 43.3%, and 9.0%, respectively, in the high risk group (p
      < 0.0001). CONCLUSIONS: The MASCC risk index is prospectively validated in a
      Chinese population. It demonstrates a better overall performance than the Talcott
      model and is equivalent to ANN model.

PMID- 20820816
TI  - Myeloid growth factor therapy in malignant lymphomas--a 5-year retrospective
      study from Hungary.
AB  - Myeloid growth factors help to prevent and cure neutropenic events in malignant
      lymphoma patients treated by chemotherapeutical regimens. Administering either
      filgrastim or pegfilgrastim, treatment schedule can be kept well and less dose
      reductions are needed, which results in better survival rates. The aim of this
      study was to examine the indications and the outcome of myeloid precursor therapy
      among our malignant lymphoma patients. Between 2003 and 2007, 249 malignant
      lymphoma patients received 1,655 cycles of different polychemotherapies. Myeloid
      growth factor therapy was administered in 138 cases by 65 patients, which meant
      8.33% of all treatment cycles and 26.1% of all patients, respectively. As for the
      indications, prevention was more common than intervention (71.7% vs. 28.3%). By
      preventive usage of growths factors, two-thirds of threatening neutropenic events
      could be avoided. Side effects were uncommon and mild: grades I-II toxicity was
      observed in 31% of all treatments. Analyzing the risk factors for febrile
      neutropenia among patients who received myeloid growth factor therapy compared to
      those who did not, we found the incidence of comorbidities, hypoalbuminemia,
      advanced stage disease, and aggressive chemotherapies significantly different in
      the two groups. Interestingly, there was no significant difference regarding the
      median age and the incidence of low body surface area. Our observations support
      that myeloid precursor therapy is an effective and safe implement to prevent or
      treat neutropenia in high-risk malignant lymphoma patients.

PMID- 20820817
TI  - Prophylactic tetracycline does not diminish the severity of epidermal growth
      factor receptor (EGFR) inhibitor-induced rash: results from the North Central
      Cancer Treatment Group (Supplementary N03CB).
AB  - PURPOSE: Previous studies suggest tetracycline and other antibiotics lessen the
      severity of epidermal growth factor receptor (EGFR) inhibitor-induced rash. This
      study sought to confirm such findings. METHODS: Patients starting an EGFR
      inhibitor were eligible for this randomized, double-blinded, placebo-controlled
      study and had to be rash-free. They were then randomly assigned to tetracycline
      500 mg orally twice a day for 28 days versus a placebo. Rash development and
      severity (monthly physician assessment and weekly patient-reported
      questionnaires), quality of life (SKINDEX-16), and adverse events were monitored
      during the 4-week intervention and then for an additional 4 weeks. The primary
      objective was to compare the incidence of grade 2 or worse rash between study
      arms; 32 patients per group provided a 90% probability of detecting a 40%
      difference in incidence with a type I error rate of 0.05 (two-sided). RESULTS:
      Sixty-five patients were enrolled, and groups were balanced on baseline
      characteristics. During the first 4 weeks, healthcare provider-reported data
      found that 27 tetracycline-treated patients (82%) and 24 placebo-exposed patients
      (75%) developed a rash. This rash was a grade 2+ in 17 (52%) and 14 (44%),
      respectively (p = 0.62). Comparable grade 2+ rash rates were observed during
      weeks 5 through 8 as well as with patient-reported rash data throughout the study
      period. Quality of life was comparable across study arms, and tetracycline was
      well tolerated. CONCLUSION: Although previous studies suggest otherwise, this
      randomized, double-blinded, placebo-controlled study did not find that
      tetracycline lessened rash incidence or severity in patients who were taking EGFR
      inhibitors.

PMID- 20820818
TI  - Sexual concerns in lung cancer patients: an examination of predictors and
      moderating effects of age and gender.
AB  - PURPOSE: Sexual concerns are understudied and undertreated for patients with lung
      cancer. Objectives were to: (1) assess sexual concerns in lung cancer patients
      and examine differences by age and gender; (2) examine stability of sexual
      concerns over time; and (3) evaluate whether sexual concerns in lung cancer
      patients are significantly related to physical and emotional symptoms. MATERIALS
      AND METHODS: Data were collected from lung cancer patients during four outpatient
      clinic visits over 6 months. Measures included sexual concerns (reduced sexual
      enjoyment, interest, or performance), fatigue (FACIT Fatigue Scale), shortness of
      breath, and emotional distress (acute distress, despair; Patient Care Monitor).
      Linear mixed model analyses were conducted. RESULTS: Sexual concerns were common,
      with 52% of patients reporting at least mild sexual concerns and were stable.
      Sexual concerns were significantly associated with physical and emotional
      symptoms; particularly strong relationships were found between sexual concerns
      and shortness of breath and emotional distress. Age moderated the relationship
      between both fatigue and shortness of breath and sexual concerns; gender
      moderated the relationship between emotional distress and sexual concerns.
      CONCLUSIONS: Self-reported sexual concerns are common in people with lung cancer,
      are stable, and are related significantly to physical and emotional symptoms; age
      and gender influence the distress associated with sexual symptoms in this
      population. Better attention to patient concerns, treatment, and more research
      are clearly needed.

PMID- 20820819
TI  - Exploring risk factors of hepatitis B virus-associated hepatocellular carcinoma:
      prospective verse retrospective studies.

PMID- 20820820
TI  - A population-based cohort study for the risk factors of HCC among hepatitis B
      virus mono-infected subjects in Japan.
AB  - BACKGROUND: There have only been a few prospective studies investigating risk
      factors associated with the development of hepatocellular carcinoma (HCC) among
      chronic hepatitis B patients all over the world, and no study has been conducted
      in Japanese population. METHODS: A population-based cohort consisting of 19393
      subjects (middle aged or older) with over 13 years' follow-up was investigated in
      Japan. RESULTS: Of 19393 subjects, 479 had hepatitis B virus (HBV) mono-infection
      (2.5%). During the 245923 person-years' follow-up (average follow-up period 12.7
      years), 13 cases of newly diagnosed HCC were documented in the HBV mono-infected
      group. Several factors at baseline (male, smoking, alanine aminotransferase, the
      positivity of HBe antigen and HB core-related antigen, the proportion of HBV DNA
      >= 5 log copies/mL, T1753V mutation, and A1762T/G1764A double mutation) were
      significantly associated with HCC among HBV mono-infected subjects. Multivariate
      adjusted Cox hazard model showed that A1762T/G1764A (hazard ratio 7.05 [95%
      confidence interval (CI) 1.03-48.12, P = 0.046]) was the only independent risk
      factor for the development of HCC. Kaplan-Meier method also showed that the
      probability of HCC occurrence-free was significantly lower in HBV mono-infected
      subjects with A1762T/G1764A double mutation than those without these mutations.
      CONCLUSION: HBV mono-infected subjects with A1762T/G1764A double mutation could
      be at high risk of HCC development during the natural course of HBV infection.

PMID- 20820821
TI  - Extended endoscopic transphenoidal approach for tuberculum sellae meningiomas.
AB  - PURPOSE: Removal of tuberculum sella (TS) meningiomas is traditionally performed
      through transcranial approaches. Wide use of the endoscope in transphenoidal
      pituitary surgery is recently accessible through the tuberculum sellae with an
      endoscope-assisted or purely endoscopic technique. Extended endoscopic approach
      is an important and alternative route for meningiomas, which are located on the
      midline originating from the tuberculum sella. However, cerebrospinal fluid (CSF)
      leakage is an important problem in extended endoscopic approaches. In this
      report, we discuss surgical limitations and nuances of endoscopic transphenoidal
      approach from a retrospective analysis of nine patients with TS meningiomas.
      METHODS: Endoscopic transphenoidal approach was performed for seven women and two
      men (mean age, 51.1 years; age range, 32-78 years) with TS meningiomas between
      July 2007 and March 2010 in the Department of Neurosurgery, Kocaeli, Turkey.
      RESULTS: Total removal was achieved in six of nine patients. An improvement of
      the preoperative visual deficits was observed in six of the nine patients.
      Multilayer closure was performed for reconstruction, and lumbar external drainage
      was used for all patients for 3-5 days. CSF leakage was not seen in any of the
      patients after the operation and removal of the drainage. CONCLUSION: Endoscopic
      extended transphenoidal approach is still not a standardized procedure for TS
      meningiomas, but it may be considered as an alternative procedure in selected
      cases.

PMID- 20820822
TI  - Variability of the S gene of hepatitis B virus in southeastern China.
AB  - In a study of 315 HBV specimens obtained from southern China, 240 (76.9%) were
      assigned to genotype B, 72 (22.9%) were genotype C, two (0.6%) were genotype A
      and one (0.3%) was genotype D. Statistical analysis revealed that variables such
      as age, gender, HBV vaccination rate, hepatitis anamnesis rate, anti-HBs and
      HBeAg prevalence and virus load were insignificant between genotype B (n = 240)
      and genotype C cases (n = 72) (P > 0.05). However, the frequency of amino acid
      (aa) substitutions in the major hydrophilic region (MHR; aa 99-169) and the
      putative HLA class I-restricted cytotoxic T lymphocyte (CTL) epitope region of
      the S gene, as well as the overlapping polymerase/RT region (aa 32-212), were
      significantly higher in genotype C group than genotype B (P < 0.001). These
      results suggest that the higher variability within genotype C carriers may
      account for the pathogenic potential.

PMID- 20820823
TI  - Molecular detection of porcine kobuviruses in pigs in Korea and their association
      with diarrhea.
AB  - Kobuviruses are small, non-enveloped viruses with a single-stranded, positive
      sense genomic RNA, belonging to the family Picornaviridae, a highly diverse
      family of important pathogens of human and other animals. Porcine kobuvirus has
      been found recently, and consequently, information about the virus is lacking. In
      this study, we identified porcine kobuviruses from pigs in Korea by RT-PCR,
      cloning and sequencing, and we showed the existence of genetic diversity among
      geographically separated porcine kobuviruses through genetic and phylogenetic
      analysis. Epidemiological studies of porcine kobuvirus linked to diarrhea
      indicated that porcine kobuvirus infections are endemic in diarrheic pigs in
      Korea. Statistical analysis of the porcine kobuvirus positive rate between
      diarrheic and healthy pigs as well as a survey for other enteric pathogens in
      diarrheic pigs suggests that porcine kobuvirus may play a role as a causative
      agent of gastroenteritis in pigs.

PMID- 20820824
TI  - Nafamostat mesilate, a potent tryptase inhibitor, modulates periodontitis in
      rats.
AB  - Previous reports have demonstrated increased tryptase-like proteolytic activity
      in the crevicular fluid of patients with periodontal disease. In the present
      study, we have investigated the effect of tryptase inhibition with nafamostat
      mesilate (NM, 6-amino-2-naphtlyl p-guanidinobenzoate dimethansulfonate) on the
      development of experimental periodontitis in rats. Eighty (80) male Wistar rats
      were randomly separated into four groups: Control group, NM group (daily 0.1
      mg/kg body weight of NM, i.p.), Ligature group (ligature placed at lower right
      first molars), and NM+Ligature group. The amount of alveolar bone loss (ABL)
      around the mesial root surface of the first mandibulary molar, as well as the
      myeloperoxidase (MPO) activity, and total proteolytic activity [N-benzoyl-L: 
      arginine-p-nitroanilide (BApNA) substrate] were determined at 7 and 14 days. NM
      led to significantly (p < 0.05) decreased ABL in animals subjected to ligature
      induced periodontitis. Tryptase inhibition prevented the onset of significant ABL
      at 7 days of experiment (0.44 +/- 0.16 and 0.60 +/- 0.22, p > 0.05, NM+Ligature
      and Control, respectively) and significantly decreased the ABL at 14 days (0.97
      +/- 0.17 versus 1.82 +/- 0.26, p < 0.001, NM+Ligature versus Ligature,
      respectively). In addition, NM significantly decreased MPO and total proteolytic
      activity at 14 days (p < 0.05). These data provided evidence that tryptase
      inhibition with NM attenuates gingival granulocyte infiltration and ABL in an
      experimental model of periodontitis in rats.

PMID- 20820825
TI  - Preference for bridging versus terminal ligands in magnesium dimers.
AB  - Magnesium dimers play important roles in inorganic and organometallic chemistry.
      This study evaluates the inherent bridging ability of a range of different
      ligands in magnesium dimers. In the first part, the Cambridge Structural Database
      is interrogated to establish the frequency of different types of ligands found in
      bridging versus terminal positions in two key structural motifs: one in which
      there are two bridging ligands (the D(2h) "Mg(2)(MU-X(2))" structure); the other
      in which there are three bridging ligands (the C(3v) "Mg(2)(MU-X(3))" structure).
      The most striking finding from the database search is the overwhelming preference
      for magnesium dimers possessing two bridging ligands. The most common bridging
      ligands are C-, N-, and O-based. In the second part, DFT calculations (at the
      B3LYP/6-311+G(d) level of theory) are carried out to examine a wider range of
      structural types for dimers consisting of the stoichiometries Mg(2)Cl(3)R and
      Mg(2)Cl(2)R(2), where R = CH(3), SiH(3), NH(2), PH(2), OH, SH, CH(2)CH(3),
      CH=CH(2), C=CH, Ph, OAc, F and Br. Consistent with the database search, the most
      stable magnesium dimers are those that contain two bridging ligands. Furthermore,
      it was demonstrated that the electronic effect of the bridging ligands is
      important in influencing the stability of the magnesium dimers. The preference
      for a bridging ligand, which reflects its ability to stabilize a magnesium dimer,
      follows the order: OH > NH(2) > C=CH > SH > Ph > Br > PH(2) = CH=CH(2) >
      CH(2)CH(3) > CH(3) > SiH(3). Finally, the role that the ether solvent Me(2)O has
      on the stability of isomeric Mg(2)Cl(2)Me(2) dimers was studied. It was found
      that the first solvent molecule stabilizes the dimers, while the second solvent
      molecule can either have a stabilizing or destabilizing effect, depending on the
      isomer structure.

PMID- 20820826
TI  - Aromaticity balance, pi-electron cooperativity and H-bonding properties in
      tautomerism of salicylideneaniline: the quantum theory of atoms in molecules
      (QTAIM) approach.
AB  - Topological analysis based on DFT calculations regarding proton transfer reaction
      in salicylideneaniline (SA) was performed to scrutinize possible changes in the
      intramolecular H-bond, pi-electron delocalization and aromaticity levels of
      certain fragments. Quantum chemical calculations and natural bond orbital (NBO)
      analyses were carried out over a tautomeric ensemble whose members correspond to
      the molecules at different stages in tautomeric interconversion of SA. The
      elaboration of intramolecular hydrogen bonding in terms of the relevant
      topological parameters and the interpretation of certain dependencies regarding
      its strength were examined. The results show that delocalization index (DI)
      between donor and acceptor atom delta(O,N) is a useful topological parameter for
      describing H-bond strength, which is influenced by pi-delocalization level within
      quasiaromatic chelate ring, indicating its resonance-assisted character. NBO
      analyses reveal that lone-pair (LP) population on N center also affects the
      strength of intramolecular H-bond in SA. Furthermore, pi-electron transfer
      accompanying intramolecular proton migration in SA is brought into being through
      formally vacant non-Lewis type LP* orbital on the tautomeric proton. As a result
      of this, tautomeric protons in molecular entities near TS have hypovalent
      character due to the lack of electron population in the bonding orbital relative
      to that in LP* orbital. While H-bonds in the tautomeric ensemble of SA are
      predominantly partial covalent, molecular entities close to transition state have
      the strongest covalent H-bonds. The most important result is also that there are
      linear correlations between the orders of bonds (hydroxyl and amine) involving
      intramolecular H-bond and electron density values at the relevant BCPs due to
      partially covalent character of these bonds, contrary to exponential behavior as
      for purely covalent bonds. Quasiaromatic chelate ring formation is established
      not only to compel a reduced aromaticity of salicylidene ring but also to
      decrease in LP-population on N.

PMID- 20820827
TI  - Comparative analysis of receptor binding by chicken and human interleukin-1beta.
AB  - Interleukin-1beta (IL-1beta) is an important cytokine in the immune system.
      Mammalian and avian IL-1betas share only 31-35% sequence identity, and the
      function of avian IL-1betas is less well understood by comparison. Although
      chicken and mammalian IL-1betas have similar tertiary structures, these ILs
      differ significantly with respect to receptor activation. Analysis of the
      structures and sequences of IL-1betas reveals that the major differences lie in
      loops. Modeling docking of chicken IL-1beta to its receptor reveals that these
      variable loops are critical for receptor binding. Molecular dynamics simulations
      of the IL-1betas reveal significant changes in the dynamic range of motion upon
      receptor binding. Loops 3 and 9 of the unbound chicken IL-1beta had greater
      fluctuations compared with the other loops. Upon binding, the flexibility of
      these loops, which directly contact the receptor, markedly decreases. Taken
      together, these results suggest that receptor binding leads to not only favorable
      enthalpy but also lower conformational entropy.

PMID- 20820828
TI  - Theoretical studies on sulfanilamide and derivatives with antibacterial activity:
      conformational and electronic analysis.
AB  - Quantum chemical methods have been used to study the conformational and
      electronic properties of sulfanilamide and derivatives with antibacterial
      activity. Calculations at B3LYP/6-311++G(3df,2p) level of theory predict the
      existence of four conformers for sulfanilamide depending on the orientation of p
      amino and amide groups. Focusing on the sulfonamide moiety, amide NH(2) and SO(2)
      groups could exist either in an eclipsed or staggered arrangement. Gas-phase
      results predict the eclipsed conformer to be most stable but opposite to what has
      been rationalized previously, no stabilizing hydrogen bonds between those groups
      has been found through NBO analysis. When solvent effect is taken into account
      through the IEF-PCM method, staggered conformer is preferred; in fact, eclipsed
      conformation changed when explicit solvent molecules were included.
      Conformational analysis of all derivatives has shown two global minima which are
      specular images. Five out of the seven derivatives studied adopted a particular
      minimum energy conformation with very similar geometries.

PMID- 20820829
TI  - Aromaticity in cyanuric acid.
AB  - This study analyzes the aromatic nature of cyanuric acid (hexahydrotriazine) and
      some of its derivatives, in terms of aromatic stabilization energy (ASE) and
      electronic behavior. The simplest molecule (C(3)N(3)O(3)H(3)) is the most
      aromatic item out of the entire set, but some of the others also display aromatic
      character. The structure of all the rings is analyzed considering their molecular
      orbitals as well as studying the inductive effect.

PMID- 20820830
TI  - A novel CLN2/TPP1 mutation in a Chinese patient with late infantile neuronal
      ceroid lipofuscinosis.

PMID- 20820831
TI  - Confirmed association between monoamine oxidase A molecular polymorphisms and
      Sudden Infant Death Syndrome.

PMID- 20820832
TI  - Time to detection of the growth of Mycobacterium tuberculosis in MGIT 960 for
      determining the early bactericidal activity of antituberculosis agents.
AB  - Evaluation of early bactericidal activity (EBA) by the determination of a fall in
      viable colony-forming units (CFU) of Mycobacterium tuberculosis in sputum is a
      first step in the clinical study of new antituberculosis agents. The time to
      detection (TTD) of growth in liquid media is more sensitive and could substitute
      for CFU counting on solid media. Overnight sputum samples collected during the
      evaluation of the novel agent TMC207 in comparison to isoniazid and rifampicin
      were studied. For the determination of CFU, we incubated 10-fold dilutions of
      homogenized sputum on selective 7H10 agar. The TTD was measured by incubating
      decontaminated sputum in the BACTEC MGIT 960 system. The fall in bacillary load
      over 7 days determined by CFU counting closely matched the prolongation of the
      TTD in the BACTEC MGIT 960 system. The CFU counts correlated significantly with
      the TTD. While the ranking of agents and different dosages of TMC207 was similar,
      the highest dose of TMC207 showed markedly better activity when measured by the
      TTD than CFU counting when compared to the activity of isoniazid. Automated TTD
      could augment, or, in future, replace, CFU counting to determine sputum bacillary
      load in EBA clinical trials pending a more formal evaluation of the correlation
      of the measurements.

PMID- 20820833
TI  - Carriage rates of methicillin-resistant Staphylococcus aureus (MRSA) depend on
      anatomic location, the number of sites cultured, culture methods, and the
      distribution of clonotypes.
AB  - The present study was carried out to determine how active surveillance for
      methicillin-resistant Staphylococcus aureus (MRSA) could be improved by the use
      of enrichment broth and the inclusion of extra-nasal sites with nares cultures.
      Molecular typing was also performed to identify colonization by single or
      multiple strains. Surveillance cultures for MRSA were obtained from 650 patients
      on admission to a medical and surgical intensive care unit (ICU) in Taiwan. MRSA
      was detected on directly plated vs. broth-enrichment cultures in any site at
      10.0% vs. 24.2%, nares 8.2% vs. 17.5%, throat 4.8% vs. 13.4%, axilla 1.2% vs.
      9.1%, and perineum 1.8% vs. 9.5%, respectively. Nares cultures alone detected
      only 81.5% and 72.5% of all colonized patients by direct and broth-enriched
      cultures, respectively. The molecular typing of 68 isolates from 17 patients
      revealed that multisite isolates were largely indistinguishable within each
      patient, but four patients had multiple subtypes and another three patients had
      different clonotypes. The detection of MRSA carriers was considerably enhanced by
      broth-enrichment cultures at multiple anatomic sites and simultaneous
      colonization by multiple strains at different sites can occur. Epidemiological
      studies are needed to determine the likelihood of subsequent nosocomial infection
      among colonized patients detected via direct nasal versus broth-enriched cultures
      from multiple sites.

PMID- 20820834
TI  - Cytokine and chemokine response in children with the 2009 pandemic influenza A
      (H1N1) virus infection.
AB  - We report the systemic cytokine and chemokine response in children with the 2009
      pandemic influenza A (H1N1) virus infection. In patients with pneumonia, the
      serum levels of IFN-gamma and IL-5 were significantly higher than those in
      patients without pneumonia. This tendency was also present for IL-6, IL-8, IL-10,
      IL-13, and MCP-1 in patients with pneumonia. Among patients with pneumonia, the
      levels of MCP-1 were significantly higher in the group of patients with pneumonia
      with severe respiratory failure than patients with mild pneumonia.

PMID- 20820835
TI  - The relationship between the symptoms of female gonococcal infections and serum
      progesterone level and the genotypes of Neisseria gonorrhoeae multi-antigen
      sequence type (NG-MAST) in Wuhan, China.
AB  - The objective of this investigation was to study the relationship between the
      symptoms of female gonococcal infections and serum progesterone level and the
      genotypes of Neisseria gonorrhoeae multi-antigen sequence type (NG-MAST) in
      Wuhan, China. Eighty-one strains of N. gonorrhoeae were harvested from the
      vaginal discharge of 975 adult females in Wuhan and were genotyped by using NG
      MAST. Serum progesterone (P) and estradiol (E(2)) levels were measured by radio
      immunoassay (RIA) in 39 gonorrhea-infected patients with slight symptoms
      (asymptomatic group) and 42 patients with conspicuous symptoms (symptomatic
      group). The average levels of serum progesterone in the asymptomatic group were
      significantly higher than in the symptomatic group (p < 0.05), while no
      significant difference was found in serum estradiol between the two groups. Of 81
      wild-type isolates, 50 NG-MAST sequence types were associated with female
      infections in Wuhan, and N. gonorrhoeae ST2951, ST735, and ST436 were principally
      found in asymptomatic patients. ST809 and ST369, however, were mainly detected in
      asymptomatic female subjects. Gonococcal genetic island (GGI)-positive and GGI
      negative strains were found in both the asymptomatic group and the symptomatic
      group. In females with gonococcal infection, high serum progesterone level is
      associated with the absence of symptoms, but no association was revealed between
      genotypes and the presence of symptoms. The GGI bears no relation to the absence
      of symptoms in the patients.

PMID- 20820836
TI  - Streptococcus equi subspecies zooepidemicus meningitis--a case report and review
      of the literature.
AB  - A case is described of a 79-year-old man, trampled by his horses, who
      subsequently developed a wound infection and, later, meningitis. Streptococcus
      equi subsp. zooepidemicus was isolated as the causative organism. S. equi subsp.
      zooepidemicus, which carries the Lancefield Group C antigen, is an uncommon human
      pathogen but is commonly isolated from bacterial infections in animals,
      particularly horses. It is most commonly acquired by humans following animal
      contact. A review of the literature identified 20 previously described cases of
      S. equi subsp. zooepidemicus meningitis. Crude mortality following infection was
      24%. All of the patients who died were over 70 years of age and the ingestion of
      unpasteurised dairy products was associated with all but one of the fatal cases.
      Hearing loss was a frequent complication, occurring in 19% of cases. Only 38% of
      patients made a complete recovery. Treatment regimes commonly included
      benzylpenicillin or a third-generation cephalosporin, with a mean treatment
      duration in survivors of 23 days.

PMID- 20820837
TI  - Correlation of mutations and recombination with growth kinetics of poliovirus
      vaccine strains.
AB  - Attenuated strains of Sabin poliovirus vaccine replicate in the human gut and, in
      rare cases, may cause vaccine-associated paralytic poliomyelitis (VAPP). The
      genetic instability of Sabin strains constitutes one of the main causes of VAPP,
      a disease that is most frequently associated with type 3 and type 2 Sabin
      strains, and more rarely with type 1 Sabin strains. In the present study, the
      growth phenotype of eight oral poliovirus vaccine (OPV) isolates (two non
      recombinants and six recombinants), as well as of Sabin vaccine strains, was
      evaluated using two different assays, the reproductive capacity at different
      temperatures (Rct) test and the one-step growth curve test in Hep-2 cells at two
      different temperatures (37 degrees C and 40 degrees C). The growth phenotype of
      isolates was correlated with genomic modifications in order to identify the
      determinants and mechanisms of reversion towards neurovirulence. All of the
      recombinant OPV isolates showed a thermoresistant phenotype in the Rct test.
      Moreover, both recombinant Sabin-3 isolates showed significantly higher viral
      yield than Sabin 3 vaccine strain at 37 degrees C and 40 degrees C in the one
      step growth curve test. All of the OPV isolates displayed mutations at specific
      sites of the viral genome, which are associated with the attenuated and
      temperature-sensitive phenotype of Sabin strains. The results showed that both
      mutations and recombination events could affect the phenotype traits of Sabin
      derivatives and may lead to the reversion of vaccinal strains to neurovirulent
      ones. The use of phenotypic markers along with the genomic analysis may shed
      additional light on the molecular determinants of the reversed neurovirulent
      phenotype of Sabin derivatives.

PMID- 20820838
TI  - Numerical investigation of nanoparticle-assisted laser-induced interstitial
      thermotherapy toward tumor and cancer treatments.
AB  - In this work, we numerically investigated nanoparticle-assisted laser-induced
      interstitial thermotherapy for tumor/cancer treatments. The goal of the study was
      to investigate the therapeutic effects of treatment conditions including laser
      wavelength, power, exposure time, concentrations of tailored nanoparticles, and
      optical/thermal properties of the tissue that is under treatment. It was found
      that using absorbing preferential nanoparticles as the photothermal agent weakens
      fluence rate distributions in terms of lowering fluence rate peaks and reducing
      laser penetration depths. However, the local enhancement in laser photon
      absorption induced by nanoparticles is so significant that the reduced fluence
      rate will be balanced out, and the eventual medical hyperthermia is greatly
      prompted by using nanoparticles. Also, the results of numerical simulations
      indicated that with constant laser illumination, an increase in nanoparticle
      concentration beyond a certain range has only an insignificant impact on
      hyperthermia.

PMID- 20820839
TI  - Pure red cell aplasia caused by parvovirus B19 in two patients without chronic
      hemolysis.
AB  - Infection with human parvovirus B19 (PVB19) induces acquired pure red cell
      aplasia (PRCA). Chronic hemolytic anemia is well known as an underlying
      condition. However, additional factors have been recognized to accompany
      parvoviral PRCA; however, there are only limited reports on iron-deficiency
      anemia (IDA) and rituximab-induced B-cell dysfunction. We report two patients
      with PVB19-associated PRCA confirmed by positivity of viral DNA. Although they
      had no chronic hemolysis, patient 1 had IDA, and patient 2 had remitted small
      lymphocytic lymphoma treated with rituximab-containing chemotherapy. Absence of
      reticulocytes in peripheral blood and marked depletion of erythroid precursors in
      bone marrow were observed both. Whereas patient 1 received only symptomatic
      therapy because anemia was not severe, patient 2 was treated with steroids, as
      PRCA etiology was at first uncertain, and immunological PRCA was not excluded.
      Both showed rapid increase of reticulocyte counts and recovery from anemia.
      Although immunoglobulin is considered effective for parvoviral PRCA, notable
      adverse reactions have been reported. When anemic symptom is not severe,
      reticulocyte observation only is recommended. The effects of steroids should also
      be re-evaluated. Optimal treatment according to disease severity remains to be
      established.

PMID- 20820840
TI  - Effects of TJN-598, a new selective phosphodiesterase type IV inhibitor on anti
      Thy1 nephritis in rats.
AB  - BACKGROUND: Phosphodiesterase type IV (PDEIV) plays an important role in the
      immune response and inflammation. However, it is well known that classical PDEIV
      inhibitors have systemic side effects, so the clinical and chronic use of these
      agents as therapy for glomerulonephritis is difficult. This study was performed
      to elucidate the anti-nephritic effects of TJN-598, a new chemical compound
      derived from herbal components, on experimental mesangial proliferative
      glomerulonephritis. METHODS: We first examined the effects of TJN-598 and
      captopril on mesangial expansion induced by anti-Thy1 serum in rats. Second, to
      investigate the effects of TJN-598 and rolipram, which are typical PDEIV
      inhibitors, on the production of tumor necrosis factor (TNF)-alpha and
      transforming growth factor (TGF)-beta1, glomeruli were isolated from rats with
      anti-Thy1 nephritis and incubated with the test drugs in vitro for 48 h. RESULTS:
      Treatment with TJN-598 prevented an increase in the mesangial area/total
      glomerular area, in the number of cells in the glomerular cross section and
      matrix index. TJN-598 also inhibited the increases in the expression of alpha
      smooth muscle actin, the TGF-beta1-positive area, in the number of ED-1 positive
      cells and proliferating cell nuclear antigen-positive cells in the glomeruli.
      Furthermore, administration of TJN-598 inhibited increases in the levels of TGF
      beta1 protein derived from glomeruli with anti-Thy-1 nephritis. The addition of
      both TJN-598 and rolipram to the culture supernatant inhibited both increased
      expression of TGF-beta1 and increases in levels of TNF-alpha in glomeruli
      isolated from rats with anti-Thy1 nephritis in a dose-dependent manner.
      CONCLUSION: These results suggest that TJN-598, a PDEIV inhibitor, is effective
      against expansion of mesangial cells, via the suppression of secretion of TGF
      beta1 and TNF-alpha from inflamed glomeruli.

PMID- 20820842
TI  - Insulin-like growth factor binding protein-related protein 1 is expressed in
      rheumatoid synovium and regulates synovial fibroblast proliferation.
AB  - Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is a
      secretory protein that shares a structural similarity with IGFBP. Studies have
      shown that IGFBP-rP1 synergistically increases fibroblast growth with insulin and
      stimulates angiogenesis in tumor tissues. In this report, we examined the
      expression and function of IGFBP-rP1 in rheumatoid arthritis (RA). IGFBP-rP1
      expression in synovial tissues was examined by reverse transcription-polymerase
      chain reaction (RT-PCR), real-time PCR, and immunohistochemical analysis. In
      vitro, IGFBP-rP1 expression was examined in synovial fibroblasts established from
      rheumatoid synovium (RASFs) by RT-PCR, Western blot, and immunostaining. The
      effect of IGFBP-rP1 small interfering RNA (siRNA) on RASF proliferation was
      assessed by alamarBlue assay. IGFBP-rP1 mRNA was detected by RT-PCR in all
      synovial tissues from RA and OA patients. In immunohistochemical analysis, IGFBP
      rP1 was mainly expressed in synovial cells in the lining layers and endothelial
      cells in the sublining layers of RA synovium. In vitro, constitutive expression
      of IGFBP-rP1 in RASFs was detected by RT-PCR, Western blot, and immunostaining.
      Treatment with IGFBP-rP1 siRNA induced a 26% decrease in RASF growth compared to
      control siRNA. A similar extent of growth-suppressive effect by IGFBP-rP1 siRNA
      was also observed when RASF proliferation was induced by TNF-alpha. Collectively,
      these data suggest that IGFBP-rP1 may regulate synovial fibroblast proliferation
      in RA.

PMID- 20820843
TI  - Peroxisome proliferator-activated receptor gamma in osteoarthritis.
AB  - Osteoarthritis (OA) is among the most prevalent chronic human health disorders
      and the most common form of arthritis. It is a leading cause of disability in
      developed countries. This disease is characterized by cartilage deterioration,
      synovitis, and remodeling of the subchondral bone. There is not yet a
      satisfactory treatment to stop or arrest this disease process. Although several
      candidates for therapeutic approaches have been put forward, recent studies
      suggest that activation of the transcription factor peroxisome proliferator
      activated receptor gamma (PPARgamma) is an interesting target for this disease.
      PPARgamma is a ligand-activated transcription factor and member of the nuclear
      receptor superfamily. Agonists of PPARgamma inhibit inflammation and reduce
      synthesis of cartilage degradation products both in vitro and in vivo, and reduce
      the development/progression of cartilage lesions in OA animal models. This review
      will highlight the recent experimental studies on the presence of PPARgamma in
      articular tissues and its effect on inflammatory and catabolic responses in
      chondrocytes and synovial fibroblasts, as well as the protective effects of
      PPARgamma ligands in arthritis experimental models. Finally, the role of
      PPARgamma polymorphism in the pathogenesis of OA and related musculoskeletal
      diseases will also be discussed.

PMID- 20820841
TI  - High-calorie diet with moderate protein restriction prevents cachexia and
      ameliorates oxidative stress, inflammation and proteinuria in experimental
      chronic kidney disease.
AB  - BACKGROUND: In earlier studies we found that a high-fat, high-energy diet (HFED)
      attenuates proteinuria, azotemia and lipid accumulation in the remnant kidney of
      rats subjected to 5/6 nephrectomy. This study was conducted to explore the
      mechanism of the salutary effect of HFED in association with moderate protein
      restriction in this model. METHODS: The 5/6 nephrectomized male rats were
      randomized to receive regular rat chow (CRF group, n = 6) or HFED diet (CRF +
      HFED, n = 7) for 12 weeks. Sham-operated rats served as controls (n = 6).
      RESULTS: The CRF group exhibited azotemia, hypertension, proteinuria, diminished
      body weight, oxidative stress, glomerulosclerosis, tubulo-interstitial
      inflammation and upregulation of pro-oxidant [NAD(P)H oxidase], pro-inflammatory
      (NF-kappaB activation, increased MCP-1, lipoxygenase, ICAM-1, VCAM-1), pro
      fibrotic (TGF-beta, CTGF) and pro-apoptotic pathways (Bax, caspase-3) in the
      remnant kidney. Consumption of the HFED resulted in a 66% increment in lipid
      intake, 8% increment in carbohydrate intake and a 24% reduction in protein
      intake. The CRF + HFED group gained weight normally, had increments in leptin and
      adiponectin levels, and despite increments in plasma cholesterol and fatty acids,
      showed significant attenuation of oxidative stress, proteinuria and inflammation,
      and partial reversal of the remnant kidney upregulation of pro-oxidant, pro
      inflammatory, pro-fibrotic and pro-apoptotic pathways. CONCLUSION: Consumption of
      high-energy diet in association with mild protein restriction results in
      suppression of upregulated pathways that drive progression of renal injury in the
      remnant kidney model. These findings may have relevance in the management of
      chronic kidney disease in humans.

PMID- 20820844
TI  - Granular Leidenfrost effect in vibrated beds with bumpy surfaces.
AB  - The effects of subjecting a bed of granular materials to horizontal vibrations by
      a bumpy oscillating surface have been investigated computationally in this study.
      The behaviour of the granular bed is determined by the vibration conditions
      applied which include the vibrating frequency and amplitude as well as the
      bumpiness of the oscillating surface. Under sufficiently vigorous vibration
      conditions, the granular Leidenfrost effect whereby the entire granular bed is
      levitated above the vibrating base by a layer of highly energetic particles may
      be observed. Granular temperature profiles of systems that exhibit the granular
      Leidenfrost effect indicate an unequal distribution of energy between particles
      near the vibrating base and those in the bulk. A bumpy oscillating surface was
      also observed to be more effective at introducing perturbations and transferring
      energy into a granular bed. The granular Leidenfrost effect can be induced by the
      application of larger grain sizes of particles constituting the bumpy vibrating
      base under vibration conditions that are normally insufficient for the onset of
      the effect. Lastly, a phase diagram which can be utilized for predicting the
      behaviours of granular beds that are subjected to oscillations by various types
      of bumpy surfaces has been constructed based on the simulation results obtained.

PMID- 20820845
TI  - Influence of reproductive traits on pollination success in two Daphne species
      (Thymelaeaceae).
AB  - Taxonomically related species can differ in a number of reproductive traits,
      which may translate into a differential mating system and pollination success.
      Here we compare two hermaphroditic insect-pollinated Daphne species (D.
      rodriguezii and D. gnidium) which differ in distribution (island endemic vs.
      mediterranean) and floral traits (long- vs. short-tube corolla). We investigated
      their mating system and pollen limitation by means of hand-pollination
      experiments and quantified the diversity and abundance of flower visitors by
      direct observations. Plant size and five reproductive traits (flower production,
      proportion of viable anthers, pollen production, flower tube length and tepal
      area) were studied to assess how they contribute to reproductive success,
      measured as proportion of pollen grains germinated per stigma and fruit set.
      Selfing was very low and pollen limitation existed in both species, though was
      higher in D. rodriguezii probably due to the scarcity of flower visitors. The low
      fruit set in both species suggests that most of the pollen grains found on
      stigmas are self-pollen. Pollinators appeared to favour some floral traits
      (specifically, flower tube length or tepal area) in both species, although flower
      crop in D. rodriguezii was the only reproductive trait influencing fruit set. In
      both species, the highest variability in reproductive traits and pollination
      success was within individuals. Our findings suggest that despite both species
      showed similar mating system, dependency on outcrossing pollen and selection of
      floral traits, pollen limitation was higher in D. rodriguezii, probably as a
      higher proportion of self-pollen arrives to its stigmas.

PMID- 20820847
TI  - The role of endosomal-recycling in long-term potentiation.
AB  - Long-term potentiation (LTP) defines persistent increases in neurotransmission
      strength at synapses that are triggered by specific patterns of neuronal
      activity. LTP, the most widely accepted molecular model for learning, is best
      characterised at glutamatergic synapses on dendritic spines. In this context, LTP
      involves increases in dendritic spine size and the insertion of glutamate
      receptors into the post-synaptic spine membrane, which together boost post
      synaptic responsiveness to neurotransmitters. In dendrites, the material required
      for LTP is sourced from an organelle termed the endosomal-recycling compartment
      (ERC), which is localised to the base of dendritic spines. When LTP is induced,
      material derived from the recycling compartment, which contains alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionate-type glutamate receptors (AMPARs), is
      mobilised into dendritic spines feeding the increased need for receptors and
      membrane at the spine neck and head. In this review, we discuss the importance of
      endosomal-recycling and the role of key proteins which control these processes in
      the context of LTP.

PMID- 20820846
TI  - Mechanistic principles of RAF kinase signaling.
AB  - The RAF family of kinases are key components acting downstream of receptor
      tyrosine kinases and cells employ several distinct mechanisms to strictly control
      their activity. RAF transitions from an inactive state, where the N-terminal
      regulatory region binds intramolecularly to the C-terminal kinase domain, to an
      open state capable of executing the phosphoryl transfer reaction. This transition
      involves changes both within and between the protein domains in RAF. Many
      different proteins regulate the transition between inactive and active states of
      RAF, including RAS and KSR, which are arguably the two most prominent regulators
      of RAF function. Recent developments have added several new twists to our
      understanding of RAF regulation. Among others, dimerization of the RAF kinase
      domain is emerging as a crucial step in the RAF activation process. The multitude
      of regulatory protein-protein interactions involving RAF remains a largely
      untapped area for therapeutic applications.

PMID- 20820848
TI  - Palmitate-induced skeletal muscle insulin resistance does not require NF-kappaB
      activation.
AB  - Palmitate activates the NF-kappaB pathway, and induces accumulation of lipid
      metabolites and insulin resistance in skeletal muscle cells. Little information
      is available whether and how these processes are causally related. Therefore, the
      objectives were to investigate whether intra-cellular lipid metabolites are
      involved in FA-induced NF-kappaB activation and/or insulin resistance in skeletal
      muscle and to investigate whether FA-induced insulin resistance and NF-kappaB
      activation are causally related. Inhibiting DGAT or CPT-1 by using, respectively,
      amidepsine or etomoxir increased DAG accumulation and sensitized myotubes to
      palmitate-induced insulin resistance. While co-incubation of palmitate with
      etomoxir increased NF-kappaB transactivation, co-incubation with amidepsine did
      not, indicating that DAG accumulation is associated with insulin resistance but
      not with NF-kappaB activation. Furthermore, pharmacological or genetic inhibition
      of the NF-kappaB pathway could not prevent palmitate-induced insulin resistance.
      In conclusion, we have demonstrated that activation of the NF-kappaB pathway is
      not required for palmitate-induced insulin resistance in skeletal muscle cells.

PMID- 20820849
TI  - Smad linker region phosphorylation in the regulation of extracellular matrix
      synthesis.
AB  - The canonical TGF-beta signalling pathway involves Smad transcription factors
      through direct serine phosphorylation of the carboxy termini, nuclear
      translocation and regulation of transcription by receptor-regulated (R)-Smad
      complexes. Smads can also be phosphorylated in the linker region most prominently
      by the action of mitogen-activated protein (MAP) kinases, which in turn have been
      activated by TGF-beta or a multitude of other growth factors and hormones. Linker
      region phosphorylation can prevent nuclear translocation of Smads and inhibit TGF
      beta signalling, potentially leading to oncogenesis. However, some evidence has
      revealed that linker region phosphorylated Smads can be translocated to the
      nucleus where they regulate transcription particularly of the synthesis of
      extracellular matrix molecules. Matrix molecules such as collagen and
      proteoglycans are involved in diseases such a fibrosis and atherosclerosis,
      respectively, and the involvement of linker region phosphorylation may represent
      a new therapeutic target.

PMID- 20820850
TI  - Comparing peripheral glial cell differentiation in Drosophila and vertebrates.
AB  - In all complex organisms, the peripheral nerves ensure the portage of information
      from the periphery to central computing and back again. Axons are in part
      amazingly long and are accompanied by several different glial cell types. These
      peripheral glial cells ensure electrical conductance, most likely nature the long
      axon, and establish and maintain a barrier towards extracellular body fluids.
      Recent work has revealed a surprisingly similar organization of peripheral nerves
      of vertebrates and Drosophila. Thus, the genetic dissection of glial
      differentiation in Drosophila may also advance our understanding of basic
      principles underlying the development of peripheral nerves in vertebrates.

PMID- 20820851
TI  - Bafilomycin A1 activates respiration of neuronal cells via uncoupling associated
      with flickering depolarization of mitochondria.
AB  - Bafilomycin A1 (Baf) induces an elevation of cytosolic Ca(2+) and acidification
      in neuronal cells via inhibition of the V-ATPase. Also, Baf uncouples
      mitochondria in differentiated PC12 ((d)PC12), (d)SH-SY5Y cells and cerebellar
      granule neurons, and markedly elevates their respiration. This respiratory
      response in (d)PC12 is accompanied by morphological changes in the mitochondria
      and decreases the mitochondrial pH, Ca(2+) and DeltaPsim. The response to Baf is
      regulated by cytosolic Ca(2+) fluxes from the endoplasmic reticulum. Inhibition
      of permeability transition pore opening increases the depolarizing effect of Baf
      on the DeltaPsim. Baf induces stochastic flickering of the DeltaPsim with a
      period of 20 +/- 10 s. Under conditions of suppressed ATP production by
      glycolysis, oxidative phosphorylation impaired by Baf does not provide cells with
      sufficient ATP levels. Cells treated with Baf become more susceptible to
      excitation with KCl. Such mitochondrial uncoupling may play a role in a number of
      (patho)physiological conditions induced by Baf.

PMID- 20820852
TI  - Cigarette smoking reprograms apical junctional complex molecular architecture in
      the human airway epithelium in vivo.
AB  - The apical junctional complex (AJC), composed of tight and adherens junctions,
      maintains epithelial barrier function. Since cigarette smoking and chronic
      obstructive pulmonary disease (COPD), the major smoking-induced disease, are
      associated with increased lung epithelial permeability, we hypothesized that
      smoking alters the transcriptional program regulating airway epithelial AJC
      integrity. Transcriptome analysis revealed global down-regulation of
      physiological AJC gene expression in the airway epithelium of healthy smokers (n
      = 59) compared to nonsmokers (n = 53) in association with changes in canonical
      epithelial differentiation pathways such as PTEN signaling accompanied by
      induction of cancer-related AJC components. The overall expression of AJC-related
      genes was further decreased in COPD smokers (n = 23). Exposure of airway
      epithelial cells to cigarette smoke extract in vitro resulted in down-regulation
      of several AJC genes paralleled by decreased transepithelial resistance. Thus,
      cigarette smoking induces transcriptional reprogramming of airway epithelial AJC
      architecture from its physiological pattern necessary for barrier function toward
      a disease-associated molecular phenotype.

PMID- 20820853
TI  - Beta-carotene affects gene expression in lungs of male and female Bcmo1 (-/-)
      mice in opposite directions.
AB  - Molecular mechanisms triggered by high dietary beta-carotene (BC) intake in lung
      are largely unknown. We performed microarray gene expression analysis on lung
      tissue of BC supplemented beta-carotene 15,15'-monooxygenase 1 knockout (Bcmo1 (
      /-)) mice, which are-like humans-able to accumulate BC. Our main observation was
      that the genes were regulated in an opposite direction in male and female Bcmo1 (
      /-) mice by BC. The steroid biosynthetic pathway was overrepresented in BC
      supplemented male Bcmo1 (-/-) mice. Testosterone levels were higher after BC
      supplementation only in Bcmo1 (-/-) mice, which had, unlike wild-type (Bcmo1
      (+/+)) mice, large variations. We hypothesize that BC possibly affects hormone
      synthesis or metabolism. Since sex hormones influence lung cancer risk, these
      data might contribute to an explanation for the previously found increased lung
      cancer risk after BC supplementation (ATBC and CARET studies). Moreover, effects
      of BC may depend on the presence of frequent human BCMO1 polymorphisms, since
      these effects were not found in wild-type mice.

PMID- 20820855
TI  - Glycoside hydrolases as components of putative carbohydrate biosensor proteins in
      Clostridium thermocellum.
AB  - The composition of the cellulase system in the cellulosome-producing bacterium,
      Clostridium thermocellum, has been reported to change in response to growth on
      different carbon sources. Recently, an extensive carbohydrate-sensing mechanism,
      purported to regulate the activation of genes coding for polysaccharide-degrading
      enzymes, was suggested. In this system, CBM modules, comprising extracellular
      components of RsgI-like anti-sigma factors, were proposed to function as
      carbohydrate sensors, through which a set of cellulose utilization genes are
      activated by the associated sigma(I)-like factors. An extracellular module of one
      of these RsgI-like proteins (Cthe_2119) was annotated as a family 10 glycoside
      hydrolase, RsgI6-GH10, and a second putative anti-sigma factor (Cthe_1471),
      related in sequence to Rsi24, was found to contain a module that resembles a
      family 5 glycoside hydrolase (termed herein Rsi24C-GH5). The present study
      examines the relevance of these two glycoside hydrolases as sensors in this
      signal-transmission system. The RsgI6-GH10 was found to bind xylan matrices but
      exhibited low enzymatic activity on this substrate. In addition, this glycoside
      hydrolase module was shown to interact with crystalline cellulose although no
      hydrolytic activity was detected on cellulosic substrates. Bioinformatic analysis
      of the Rsi24C-GH5 showed a glutamate-to-glutamine substitution that would
      presumably preclude catalytic activity. Indeed, the recombinant module was shown
      to bind to cellulose, but showed no hydrolytic activity. These observations
      suggest that these two glycoside hydrolases underwent an evolutionary adaptation
      to function as polysaccharide binding agents rather than enzymatic components and
      thus serve in the capacity of extracellular carbohydrate sensors.

PMID- 20820854
TI  - Helicobacter pylori: a ROS-inducing bacterial species in the stomach.
AB  - BACKGROUND: Reactive oxygen species (ROS) and reactive nitrogen species (RNS)
      have been reported to impact gastric inflammation and carcinogenesis. However,
      the precise mechanism by which Helicobacter pylori induces gastric carcinogenesis
      is presently unclear. AIM: This review focuses on H. pylori-induced ROS/RNS
      production in the host stomach, and its relationship with gastric carcinogenesis.
      RESULTS: Activated neutrophils are the main source of ROS/RNS production in the
      H. pylori-infected stomach, but H. pylori itself also produces ROS. In addition,
      extensive recent studies have revealed that H. pylori-induced ROS production in
      gastric epithelial cells might affect gastric epithelial cell signal
      transduction, resulting in gastric carcinogenesis. Excessive ROS/RNS production
      in the stomach can damage DNA in gastric epithelial cells, implying its
      involvement in gastric carcinogenesis. CONCLUSION: Understanding the molecular
      mechanism behind H. pylori-induced ROS, and its involvement in gastric
      carcinogenesis, is important for developing new strategies for gastric cancer
      chemoprevention.

PMID- 20820856
TI  - A study on using fireclay as a biomass carrier in an activated sludge system.
AB  - By adding a biomass carrier to an activated sludge system, the biomass
      concentration will increase, and subsequently the organic removal efficiency will
      be enhanced. In this study, the possibility of using excess sludge from ceramic
      and tile manufacturing plants as a biomass carrier was investigated. The aim of
      this study was to determine the effect of using fireclay as a biomass carrier on
      biomass concentration, organic removal and nitrification efficiency in an
      activated sludge system. Experiments were conducted by using a bench scale
      activated sludge system operating in batch and continuous modes. Artificial
      simulated wastewater was made by using recirculated water in a ceramic
      manufacturing plant. In the continuous mode, hydraulic detention time in the
      aeration reactor was 8 and 22 h. In the batch mode, aeration time was 8 and 16 h.
      Fireclay doses were 500, 1,400 and 2,250 mg l(-1), and were added to the reactors
      in each experiment separately. The reactor with added fireclay was called a
      Hybrid Biological Reactor (HBR). A reactor without added fireclay was used as a
      control. Efficiency parameters such as COD, MLVSS and nitrate were measured in
      the control and HBR reactors according to standard methods. The average
      concentration of biomass in the HBR reactor was greater than in the control
      reactor. The total biomass concentration in the HBR reactor (2.25 g l(-1)
      fireclay) in the continuous mode was 3,000 mg l(-1) and in the batch mode was
      2,400 mg l(-1). The attached biomass concentration in the HBR reactor (2.25 g l(
      1) fireclay) in the continuous mode was 1,500 mg l(-1) and in the batch mode was
      980 mg l(-1). Efficiency for COD removal in the HBR and control reactor was 95
      and 55%, respectively. In the HBR reactor, nitrification was enhanced, and the
      concentration of nitrate was increased by 80%. By increasing the fireclay dose,
      total and attached biomass was increased. By adding fireclay as a biomass
      carrier, the efficiency of an activated sludge system to treat wastewater from
      ceramic manufacturing plants was increased.

PMID- 20820857
TI  - Quantification of phototrophic biomass on rocks: optimization of chlorophyll-a
      extraction by response surface methodology.
AB  - Biological colonization of rock surfaces constitutes an important problem for
      maintenance of buildings and monuments. In this work, we aim to establish an
      efficient extraction protocol for chlorophyll-a specific for rock materials, as
      this is one of the most commonly used biomarkers for quantifying phototrophic
      biomass. For this purpose, rock samples were cut into blocks, and three different
      mechanical treatments were tested, prior to extraction in dimethyl sulfoxide
      (DMSO). To evaluate the influence of the experimental factors (1) extractant-to
      sample ratio, (2) temperature, and (3) time of incubation, on chlorophyll-a
      recovery (response variable), incomplete factorial designs of experiments were
      followed. Temperature of incubation was the most relevant variable for
      chlorophyll-a extraction. The experimental data obtained were analyzed following
      a response surface methodology, which allowed the development of empirical models
      describing the interrelationship between the considered response and experimental
      variables. The optimal extraction conditions for chlorophyll-a were estimated,
      and the expected yields were calculated. Based on these results, we propose a
      method involving application of ultrasound directly to intact sample, followed by
      incubation in 0.43 ml DMSO/cm(2) sample at 63 degrees C for 40 min. Confirmation
      experiments were performed at the predicted optimal conditions, allowing
      chlorophyll-a recovery of 84.4 +/- 11.6% (90% was expected), which implies a
      substantial improvement with respect to the expected recovery using previous
      methods (68%). This method will enable detection of small amounts of
      photosynthetic microorganisms and quantification of the extent of biocolonization
      of stone surfaces.

PMID- 20820858
TI  - Differences in stationary-phase cells of a commercial Saccharomyces cerevisiae
      wine yeast grown in aerobic and microaerophilic batch cultures assessed by
      electric particle analysis, light diffraction and flow cytometry.
AB  - We applied electric particle analysis, light diffraction and flow cytometry to
      obtain information on the morphological changes during the stationary phase of
      Saccharomyces cerevisiae. The reported analyses of S. cerevisiae populations were
      obtained under two different conditions, aerobic and microaerophilic, at 27
      degrees C. The samples analysed were taken at between 20 and 50 h from the
      beginning of culture. To assist in the interpretation of the observed
      distributions a complexity index was used. The aerobically grown culture reached
      significantly greater cell density. Under these conditions, the cell density
      experienced a much lower reduction (3%) compared with the microaerophilic
      conditions (30%). Under aerobic conditions, the mean cell size determined by both
      electric particle analysis and light diffraction was lower and remained similar
      throughout the experiment. Under microaerophilic conditions, the mean cell size
      determined by electric particle analysis decreased slightly as the culture
      progressed through the stationary phase. Forward and side scatter distributions
      revealed two cell subpopulations under both growth conditions. However, in the
      aerobic growing culture the two subpopulations were more separated and hence
      easier to distinguish. The distributions obtained with the three experimental
      techniques were analysed using the complexity index. This analysis suggested that
      a complexity index is a good descriptor of the changes that take place in a yeast
      population in the stationary phase, and that it aids in the discussion and
      understanding of the implications of these distributions obtained by these
      experimental techniques.

PMID- 20820859
TI  - Evaluation and optimization of ethanol production from carob pod extract by
      Zymomonas mobilis using response surface methodology.
AB  - In this research, ethanol production from carob pod extract (extract) using
      Zymomonas mobilis with medium optimized by Plackett-Burman (P-B) and response
      surface methodologies (RSM) was studied. Z. mobilis was recognized as useful for
      ethanol production from carob pod extract. The effects of initial concentrations
      of sugar, peptone, and yeast extract as well as agitation rate (rpm), pH, and
      culture time in nonhydrolyzed carob pod extract were investigated. Significantly
      affecting variables (P = 0.05) in the model obtained from RSM studies were:
      weights of bacterial inoculum, initial sugar, peptone, and yeast extract. Acid
      hydrolysis was useful to complete conversion of sugars to glucose and fructose.
      Nonhydrolyzed extract showed higher ethanol yield and residual sugar compared
      with hydrolyzed extract. Ethanol produced (g g(-1) initial sugar, as the
      response) was not significantly different (P = 0.05) when Z. mobilis performance
      was compared in hydrolyzed and nonhydrolyzed extract. The maximum ethanol of 0.34
      +/- 0.02 g g(-1) initial sugar was obtained at 30 degrees C, initial pH 5.2, and
      80 rpm, using concentrations (g per 50 mL culture media) of: inoculum bacterial
      dry weight, 0.017; initial sugar, 5.78; peptone, 0.43; yeast extract, 0.43; and
      culture time of 36 h.

PMID- 20820860
TI  - Phytostimulation and biofertilization in wheat by cyanobacteria.
AB  - Cyanobacteria are commonly used for the phytostimulation and biofertilization of
      agriculture crops due to their nitrogen-fixing ability. However, the contribution
      by their phytohormones has been neglected. This study focuses on the screening of
      rhizospheric and free-living cyanobacteria for in vitro phytohormones production
      and growth stimulation in wheat. Selected isolates were shown to release
      cytokinin and indole-3-acetic acid (IAA) by using UPLC coupled with MS/MS via an
      electrospray interface. The maximum cytokinin and IAA concentration was 22.7 pmol
      mg(-1) ch-a and 38 pmol mg(-1) ch-a, respectively, in the culture medium of
      Chroococcidiopsis sp. Ck4 and Anabaena sp. Ck1. The growth of wheat inoculated
      with cyanobacterial strains was stimulated under axenic as well as field
      conditions. Seed germination, shoot length, tillering, number of lateral roots,
      spike length, and grain weight were significantly enhanced in inoculated plants.
      The maximum increase in grain weight (43%) was demonstrated in wheat plants
      inoculated with Chroococcidiopsis sp. Ck4 under natural conditions. Positive
      linear correlation of cyanobacterial cytokinin with shoot length (r = 0.608; P =
      0.01), spike length (r = 0.682; P = 0.01), and grain weight (r = 0.0.869; P =
      0.01) was recorded. Similarly, cyanobacterial IAA was correlated with the root
      growth parameters shoot length (r = 0.588; P = 0.01), spike length (r = 0.0.689;
      P = 0.01), and weight of seeds (r = 0.480; P = 0.05). The endogenous
      phytohormones pool of the plant was enhanced significantly as a result of the
      plant-cyanobacteria association in the rhizosphere. It was concluded that
      cyanobacterial phytohormones are a major tool for improved growth and yield in
      wheat.

PMID- 20820861
TI  - Transcriptional repression by Kluyveromyces lactis Tup1 in Saccharomyces
      cerevisiae.
AB  - The general repression complex, constituted by the yeast Tup1 and Ssn6 factors,
      is a conserved global regulator of transcription in eukaryotes. In the yeast
      Saccharomyces cerevisiae, it is an important repressor of hypoxic genes, such as
      ANB1, under aerobic conditions and deletion of the TUP1 gene causes a
      flocculation phenotype. The KlTUP1 gene from the yeast Kluyveromyces lactis
      encodes for a protein with 83% similarity to Tup1 in S. cerevisiae. Despite the
      general domain conservation, the database searches showed the absence of a
      characteristic Tup1 glutamine-rich domain (Q1 at positions 96-116). Instead,
      there was a non-conserved sequence lacking the alpha-helix structure in this
      region. The ability to act as a transcriptional repressor was tested by
      expressing the KlTUP1 gene, in both high- and low-copy vectors, in an S.
      cerevisiae tup1 mutant strain. Repression effects were studied using the aerobic
      repressible reporter ANB1-lacZ and the effect on flocculation. In both regulatory
      systems, low levels of KlTup1 caused moderate (~30%) repression, but when the
      number of KlTup1 copies was increased, only the ANB1 reporter raised the
      repression levels of S. cerevisiae Tup1. These results show the capability of
      KlTup1 to act as a repressor in S. cerevisiae. The lower repression reached in S.
      cerevisiae is discussed in terms of structural differences.

PMID- 20820862
TI  - Fungal microbiota from rain water and pathogenicity of Fusarium species isolated
      from atmospheric dust and rainfall dust.
AB  - In order to determine the presence of Fusarium spp. in atmospheric dust and
      rainfall dust, samples were collected during September 2007, and July, August,
      and October 2008. The results reveal the prevalence of airborne Fusarium species
      coming from the atmosphere of the South East coast of Spain. Five different
      Fusarium species were isolated from the settling dust: Fusarium oxysporum, F.
      solani, F. equiseti, F. dimerum, and F. proliferatum. Moreover, rainwater samples
      were obtained during significant rainfall events in January and February 2009.
      Using the dilution-plate method, 12 fungal genera were identified from these
      rainwater samples. Specific analyses of the rainwater revealed the presence of
      three species of Fusarium: F. oxysporum, F. proliferatum and F. equiseti. A total
      of 57 isolates of Fusarium spp. obtained from both rainwater and atmospheric
      rainfall dust sampling were inoculated onto melon (Cucumis melo L.) cv. Pinonet
      and tomato (Lycopersicon esculentum Mill.) cv. San Pedro. These species were
      chosen because they are the main herbaceous crops in Almeria province. The
      results presented in this work indicate strongly that spores or propagules of
      Fusarium are able to cross the continental barrier carried by winds from the
      Sahara (Africa) to crop or coastal lands in Europe. Results show differences in
      the pathogenicity of the isolates tested. Both hosts showed root rot when
      inoculated with different species of Fusarium, although fresh weight measurements
      did not bring any information about the pathogenicity. The findings presented
      above are strong indications that long-distance transmission of Fusarium
      propagules may occur. Diseases caused by species of Fusarium are common in these
      areas. They were in the past, and are still today, a problem for greenhouses
      crops in Almeria, and many species have been listed as pathogens on agricultural
      crops in this region. Saharan air masses dominate the Mediterranean regions. The
      evidence of long distance dispersal of Fusarium spp. by atmospheric dust and
      rainwater together with their proved pathogenicity must be taken into account in
      epidemiological studies.

PMID- 20820863
TI  - Inhibitory action of toxic compounds present in lignocellulosic hydrolysates on
      xylose to xylitol bioconversion by Candida guilliermondii.
AB  - The inhibitory action of acetic acid, ferulic acid, and syringaldehyde on
      metabolism of Candida guilliermondii yeast during xylose to xylitol bioconversion
      was evaluated. Assays were performed in buffered and nonbuffered semidefined
      medium containing xylose as main sugar (80.0 g/l), supplemented or not with
      acetic acid (0.8-2.6 g/l), ferulic acid (0.2-0.6 g/l), and/or syringaldehyde (0.3
      0.8 g/l), according to a 2(3) full factorial design. Since only individual
      effects of the variables were observed, assays were performed in a next step in
      semidefined medium containing different concentrations of each toxic compound
      individually, for better understanding of their maximum concentration that can be
      present in the fermentation medium without affecting yeast metabolism. It was
      concluded that acetic acid, ferulic acid, and syringaldehyde are compounds that
      may affect Candida guilliermondii metabolism (mainly cell growth) during
      bioconversion of xylose to xylitol. Such results are of interest and reveal that
      complete removal of toxic compounds from the fermentation medium is not necessary
      to obtain efficient conversion of xylose to xylitol by Candida guilliermondii.
      Fermentation in buffered medium was also considered as an alternative to overcome
      the inhibition caused by these toxic compounds, mainly by acetic acid.

PMID- 20820864
TI  - Nickel(II) biosorption by Rhodotorula glutinis.
AB  - The present study reports the feasibility of using Rhodotorula glutinis biomass
      as an alternative low-cost biosorbent to remove Ni(II) ions from aqueous
      solutions. Acetone-pretreated R. glutinis cells showed higher Ni(II) biosorption
      capacity than untreated cells at pH values ranging from 3 to 7.5, with an optimum
      pH of 7.5. The effects of other relevant environmental parameters, such as
      initial Ni(II) concentration, shaking contact time and temperature, on Ni(II)
      biosorption onto acetone-pretreated R. glutinis were evaluated. Significant
      enhancement of Ni(II) biosorption capacity was observed by increasing initial
      metal concentration and temperature. Kinetic studies showed that the kinetic data
      were best described by a pseudo-second-order kinetic model. Among the two-, three
      , and four-parameter isotherm models tested, the Fritz-Schluender model exhibited
      the best fit to experimental data. Thermodynamic parameters (activation energy,
      and changes in activation enthalpy, activation entropy, and free energy of
      activation) revealed that the biosorption of Ni(II) ions onto acetone-pretreated
      R. glutinis biomass is an endothermic and non-spontaneous process, involving
      chemical sorption with weak interactions between the biosorbent and Ni(II) ions.
      The high sorption capacity (44.45 mg g(-1) at 25 degrees C, and 63.53 mg g(-1) at
      70 degrees C) exhibited by acetone-pretreated R. glutinis biomass places this
      biosorbent among the best adsorbents currently available for removal of Ni(II)
      ions from aqueous effluents.

PMID- 20820865
TI  - A stress response related to the carbon source and the absence of KlHAP2 in
      Kluyveromyces lactis.
AB  - The Kluyveromyces lactis HIS4 gene (KlHIS4) is transcriptionally regulated by the
      carbon source. The promoter region encompassing positions -238 to -139 is
      responsible for this regulation according to lacZ reporter assays.
      Electrophoretic Mobility Shift Assay (EMSA) experiments on KlHIS4 promoter
      (positions -218 to -213, Fragment 6, F6) show a specific gel-shift band, CS1,
      whose intensity is carbon-source dependent in K. lactis hap2 (klhap2) knock-out
      strains. The klhap3 mutation is not able to cause this effect by itself, but the
      combination of klhap2 and klhap3 mutations has an enhanced effect on CS1 band
      formation. Introducing a heat shock element (HSE) at the sequence in the F6
      fragment (mutated F6, F6*) increases the binding activity in the klhap2 mutant.
      KlHIS4 mRNA levels in the klhap2 or the double Klhap2/3p mutant do not correlate
      with the increase in CS1 binding activity, indicating that the factor causing CS1
      is acting and only detectable in vitro. EMSA experiments with K. lactis wild-type
      cells under temperature stress conditions show a band enhancement (Ts1), similar
      in size to CS1. Cross-competition experiments between F6 and F6* show that F6*
      competes more efficiently than F6 for both CS1 and Ts1 formation, indicating the
      involvement of the HSE in the formation of the specific gel-shift bands.
      Moreover, the similar gel-shift patterns suggest that both bands are caused by
      the same heat shock-like factor under different stress conditions. Therefore, the
      enhancement of the CS1 band signal in the klhap2 (and klhap2/3) mutants is due to
      the increase in heat shock-like factors in the protein extracts from these mutant
      cells grown in a non-fermentable carbon source. This Klhap2-dependent stress
      effect was not previously described in K. lactis.

PMID- 20820866
TI  - Effect of biofumigation with manure amendments and repeated biosolarization on
      Fusarium densities in pepper crops.
AB  - In the region of Murcia (southeast Spain), sweet pepper has been grown as a
      monoculture in greenhouses for many years. Until 2005, when it was banned, soils
      were disinfested with methyl bromide (MB) to control pathogens and to prevent
      soil fatigue effects. The genus Fusarium plays an important role in the
      microbiological component associated with yield decline in pepper monocultures.
      In the present study, soils were treated with manure amendments, alone
      (biofumigation, B) or in combination with solarization (biosolarization, BS),
      with or without the addition of pepper plant residues. The B and BS treatments
      were compared with a treatment using MB. The extent of disinfestation was
      measured from the density of Fusarium spp. isolated from the soil before and
      after the respective treatments. Three different species were systematically
      isolated: Fusarium oxysporum, Fusarium solani and Fusarium equiseti. The repeated
      use of manure amendments with pepper crop residues, without solarization, was
      unable to decrease the Fusarium spp. density (which increased from 2,047.17 CFU
      g(-1) to 3,157.24 CFU g(-1) before and after soil disinfestation, respectively),
      unlike MB-treated soil (in which the fungi decreased from 481.39 CFU g(-1) to
      23.98 CFU g(-1)). However, the effectiveness of the repeated application of BS in
      diminishing doses (with or without adding plant residues) on Fusarium populations
      (reductions greater than 72%) was similar to or even greater than the effect of
      MB.

PMID- 20820867
TI  - Characterization of Bacillus phage-K2 isolated from chungkookjang, a fermented
      soybean foodstuff.
AB  - An investigation of a virulent Bacillus phage-K2 (named Bp-K2) isolated from
      chungkookjang (a fermented soybean foodstuff) was made. Bp-K2 differed in
      infectivity against a number of Bacillus subtilis strains including starter
      strains of chungkookjang and natto, being more infectious to Bacillus strains
      isolated from the chungkookjang, but much less active against a natto strain. Bp
      K2 is a small DNA phage whose genome size is about 21 kb. Bp-K2 is a tailed
      bacteriophage with an isometric icosahedral head (50 nm long on the lateral side,
      80 nm wide), a long contractile sheath (85-90 nm * 28 nm), a thin tail fiber (80
      85 nm long, 10 nm wide), and a basal plate (29 nm long, 47 nm wide) with a number
      of spikes, but no collar. The details of the structures of Bp-K2 differ from
      natto phage phiBN100 as well as other known Bacillus phages such as SPO1-like or
      phi 29-like viruses. These data suggest that Bp-K2 would be a new member of the
      Myoviridae family of Bacillus bacteriophages.

PMID- 20820868
TI  - Mannitol production by lactic acid bacteria grown in supplemented carob syrup.
AB  - Detailed kinetic and physiological characterisation of eight mannitol-producing
      lactic acid bacteria, Leuconostoc citreum ATCC 49370, L. mesenteroides subsp.
      cremoris ATCC19254, L. mesenteroides subsp. dextranicum ATCC 19255, L. ficulneum
      NRRL B-23447, L. fructosum NRRL B-2041, L. lactis ATCC 19256, Lactobacillus
      intermedius NRRL 3692 and Lb. reuteri DSM 20016, was performed using a carob
      based culture medium, to evaluate their different metabolic capabilities.
      Cultures were thoroughly followed for 30 h to evaluate consumption of sugars, as
      well as production of biomass and metabolites. All strains produced mannitol at
      high yields (>0.70 g mannitol/g fructose) and volumetric productivities (>1.31
      g/l h), and consumed fructose and glucose simultaneously, but fructose
      assimilation rate was always higher. The results obtained enable the studied
      strains to be divided mainly into two groups: one for which glucose assimilation
      rates were below 0.78 g/l h (strains ATCC 49370, ATCC 19256 and ATCC 19254) and
      the other for which they ranged between 1.41 and 1.89 g/l h (strains NRRL B-3692,
      NRRL B-2041, NRRL B-23447 and DSM 20016). These groups also exhibited different
      mannitol production rates and yields, being higher for the strains with faster
      glucose assimilation. Besides mannitol, all strains also produced lactic acid and
      acetic acid. The best performance was obtained for L. fructosum NRRL B-2041, with
      maximum volumetric productivity of 2.36 g/l h and the highest yield,
      stoichiometric conversion of fructose to mannitol.

PMID- 20820869
TI  - The detection of CMV pp65 and IE1 in glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) is a highly lethal brain tumor affecting children
      and adults, with the majority of affected individuals dying from their disease by
      2 years following diagnosis. Other groups have reported the association of
      cytomegalovirus (CMV) with GBM, and we sought to confirm these findings in a
      large series of patients with primary GBM from our institution.
      Immunohistochemical analysis of paraffin embedded tissue sections was performed
      on 49 newly diagnosed GBM tumors, the largest series reported to date. We
      confirmed the presence of CMV pp65 on 25/49 (51%) and of IE1 on 8/49 (16%) of
      these tumors. While pp65 and IE1 are generally found in the nucleus of cells that
      are permissibly infected by CMV, GBM in this series had mostly cytoplasmic
      staining, with only 16% having nuclear staining for one or both of these
      antigens. We infected GBM cell lines with a laboratory strain of CMV, and found
      that most of the staining was cytoplasmic, with some perinuclear localization of
      IE1. To test the potential for CMV infected GBM cells to be recognized by CMV
      pp65 and IE1 specific cytotoxic T lymphocytes (CTL), we used CMV infected GBM
      cell lines in cytotoxicity assays with human leukocyte antigen partially matched
      CMV CTL. Lysis of CMV infected GBM tumor cells was accentuated by pre-treating
      these cell lines with either the demethylating agent decitabine or interferon
      gamma, both of which were shown to increase MHC Class I and II expression on
      tumor cells in vitro. These studies confirm the presence of CMV pp65 or IE1 on
      approximately half of GBM, with the possibility that CMV positive tumor cells can
      be recognized by CMV pp65/IE1 specific T cells.

PMID- 20820870
TI  - Genomic aberrations associated with outcome in anaplastic oligodendroglial tumors
      treated within the EORTC phase III trial 26951.
AB  - Despite similar morphological aspects, anaplastic oligodendroglial tumors (AOTs)
      form a heterogeneous clinical subgroup of gliomas. The chromosome arms 1p/19q
      codeletion has been shown to be a relevant biomarker in AOTs and to be perfectly
      exclusive from EGFR amplification in gliomas. To identify new genomic regions
      associated with prognosis, 60 AOTs from the EORTC trial 26951 were analyzed
      retrospectively using BAC-array-based comparative genomic hybridization. The data
      were processed using a binary tree method. Thirty-three BACs with prognostic
      value were identified distinguishing four genomic subgroups of AOTs with
      different prognosis (p < 0.0001). Type I tumors (25%) were characterized by: (1)
      an EGFR amplification, (2) a poor prognosis, (3) a higher rate of necrosis, and
      (4) an older age of patients. Type II tumors (21.7%) had: (1) loss of prognostic
      BACs located on 1p tightly associated with 19q deletion, (2) a longer survival,
      (3) an oligodendroglioma phenotype, and (4) a frontal location in brain. Type III
      AOTs (11.7%) exhibited: (1) a deletion of prognostic BACs located on 21q, and (2)
      a short survival. Finally, type IV tumors (41.7%) had different genomic patterns
      and prognosis than type I, II and III AOTs. Multivariate analysis showed that
      genomic type provides additional prognostic data to clinical, imaging and
      pathological features. Similar results were obtained in the cohort of 45
      centrally reviewed-validated cases of AOTs. Whole genome analysis appears useful
      to screen the numerous genomic abnormalities observed in AOTs and to propose new
      biomarkers particularly in the non-1p/19q codeleted AOTs.

PMID- 20820871
TI  - Wilms' tumor 1 silencing decreases the viability and chemoresistance of
      glioblastoma cells in vitro: a potential role for IGF-1R de-repression.
AB  - Wilms' tumor 1 (WT1) is a transcription factor with a multitude of downstream
      targets that have wide-ranging effects in non-glioma cell lines. Though its
      expression in glioblastomas is now well-documented, the role of WT1 in these
      tumors remains poorly defined. We hypothesized that WT1 functions as an oncogene
      to enhance glioblastoma viability and chemoresistance. WT1's role was examined by
      studying the effect of WT1 silencing and overexpression on DNA damage, apoptosis
      and cell viability. Results indicated that WT1 silencing adversely affected
      glioblastoma viability, at times, in synergy with 1,3-bis(2-chloroethyl)-1
      nitrosourea (BCNU) and cisplatin. To investigate other mechanisms through which
      WT1 could affect viability, we measured cell cycle distribution, senescence, and
      autophagy. WT1 silencing had no effect on these processes. Lastly, we examined
      WT1 regulation of IGF-1R expression. Counterintuitively, upregulation of IGF-1R
      was evident after WT1 silencing. In conclusion, WT1 functions as a survival
      factor in glioblastomas, possibly through inhibition of IGF-1R expression.

PMID- 20820872
TI  - Whole-genomic survey of oligodendroglial tumors: correlation between allelic
      imbalances and gene expression profiles.
AB  - Malignant gliomas are the most common subtype of primary central nervous system
      (CNS) tumors. Their pathological classification, however, remains subjective,
      stimulating researchers to actively seek objective molecular markers to discover
      alternative and more reproducible tools for improved subtypification. Herein, we
      present a global survey of genomic alterations in oligodendroglial tumors (OT).
      Genetic and epigenetic alterations identified in this study are correlated with
      OT molecular groups we have recently reported: a neurogenic group composed of
      tumors with loss of heterozygosity (LOH) at 1p-19q, IDH1 mutations, and MGMT
      promoter methylation, showing good prognosis; an intermediate group, presenting
      TP53 mutations or LOH at 17p, IDH1 mutations, and GSTP1 promoter methylation; and
      a proliferative group, presenting major genetic alterations (LOH at 10q, EGFR
      amplification, and CDKN2A/ARF deletion) and poor prognosis. These results allowed
      us to refine our molecular characterization associated with prognosis, referring
      exclusively to oligodendroglial tumors.

PMID- 20820873
TI  - Expression of O6-methylguanine-DNA methyltransferase in childhood
      medulloblastoma.
AB  - Medulloblastomas (MB) are the most common malignant brain tumors in childhood.
      Alkylator-based drugs are effective agents in the treatment of patients with MB.
      In several tumors, including malignant glioma, elevated O(6)-methylguanine-DNA
      methyltransferase (MGMT) expression levels or lack of MGMT promoter methylation
      have been found to be associated with resistance to alkylating chemotherapeutic
      agents such as temozolomide (TMZ). In this study, we examined the MGMT status of
      MB and central nervous system primitive neuroectodermal tumor (PNET) cells and
      two large sets of primary MB. In seven MB/PNET cell lines investigated, MGMT
      promoter methylation was detected only in D425 human MB cells as assayed by the
      qualitative methylation-specific PCR and the more quantitative pyrosequencing
      assay. In D425 human MB cells, MGMT mRNA and protein expression was clearly lower
      when compared with the MGMT expression in the other MB/PNET cell lines. In
      MB/PNET cells, sensitivity towards TMZ and 1-(2-chloroethyl)-3-cyclohexyl-1
      nitrosourea (CCNU) correlated with MGMT methylation and MGMT mRNA expression.
      Pyrosequencing in 67 primary MB samples revealed a mean percentage of MGMT
      methylation of 3.7-92% (mean: 13.25%, median: 10.67%). Percentage of MGMT
      methylation and MGMT mRNA expression as determined by quantitative RT-PCR
      correlated inversely (n = 46; Pearson correlation r (2) = 0.14, P = 0.01). We
      then analyzed MGMT mRNA expression in a second set of 47 formalin-fixed paraffin
      embedded primary MB samples from clinically well-documented patients treated
      within the prospective randomized multicenter trial HIT'91. No association was
      found between MGMT mRNA expression and progression-free or overall survival.
      Therefore, it is not currently recommended to use MGMT mRNA expression analysis
      to determine who should receive alkylating agents and who should not.

PMID- 20820874
TI  - Health-related quality of life and cognitive functioning in adult patients with
      supratentorial WHO grade II glioma: status prior to therapy.
AB  - The present prospective study intends to evaluate health-related quality of life
      (HRQL) and cognitive functioning in adult patients with supratentorial World
      Health Organization (WHO) grade II glioma (LGG) prior to observation/therapy and
      to determine possible influences of tumor-related factors on these measures.
      Adult patients with biopsy-proven supratentorial LGG were considered eligible
      (study period 18 months). Besides detailed documentation of patient clinical
      status we evaluated HRQL using the Short Form-36 (SF-36) Health Survey and
      applied the Beck Depression Inventory. Furthermore, attention and verbal memory
      functions were tested. Data from matched healthy control populations served as
      reference, and T-values were compared using Mann-Whitney U tests. For correlation
      of scores the Pearson test was utilized. Thirty-three patients with median
      Karnofsky Performance Status (KPS) of 80 were evaluated. Selective and divided
      attention showed significant impairment (P < 0.005), while verbal memory
      functions were unaffected. HRQL evaluated by SF-36 Health Survey was
      significantly reduced predominantly in the psychological domains (P < 0.025 to P
      < 0.0005). Nine patients displayed mild to moderate depression. Duration of
      symptoms >20 weeks and presence of seizures negatively affected aspects of HRQL,
      while cognitive functions were not influenced. KPS <80 correlated significant
      only with reduced physical functioning (P < 0.002) and role functioning (P <
      0.01) on the SF-36 Health Survey. While displaying good clinical status, patients
      with LGG showed significant impairment in aspects of attention and affections of
      HRQL already at time of diagnosis. These results suggest that these impairments
      originate from the tumor and/or potentially from confrontation with the diagnosis
      itself.

PMID- 20820876
TI  - Molecular cloning and characterization of an achene-seed-specific promoter from
      motherwort (Leonurus japonicus Houtt).
AB  - LJAMP1 is a small antimicrobial protein purified previously from the seeds of
      motherwort, and it is expressed preferentially in seeds. A 794-bp upstream
      sequence of the ATG start codon was isolated using a genome walking method and
      cloned into the upstream of the beta-glucuronidase (GUS) reporter gene to
      determine the GUS tissue-specific expression pattern. The transgenic tobacco
      showed that pLJAMP1 promoter derived GUS reporter gene special expression in
      pollen, achene and seed. The analysis of cis-acting elements also revealed
      pLJAMP1 promoter contained pollen and seed related transcriptional control
      elements.

PMID- 20820877
TI  - Synthesis of double-layered rotavirus-like particles using internal ribosome
      entry site vector system in stably-transformed Drosophila melanogaster.
AB  - We established a bicistronic expression system using an encephalomyocarditis
      virus (EMCV)-derived internal ribosomal entry site (IRES) element to generate
      stably transformed Drosophila melanogaster Schneider 2 (S2) cells expressing
      human rotavirus Wa capsid proteins, VP2 and VP6, for the synthesis of VP2/6
      double-layered virus-like particle (DVLP). The EMCV-derived IRES permitted
      bicistronic translation of recombinant VP6. Recombinant VP2 and VP6 were detected
      in extracellular fractions of stably transformed S2 cells. A wheel-like DVLP
      (diam ~ 50-55 nm) with short spikes was produced from the extracellular fraction
      of stably transformed S2 cells. A bicistronic expression system using an EMCV
      derived IRES element can thus be used to express two proteins of interest in
      stably transformed S2 cells. The bi-or tri-cistronic expression of recombinant
      VP2/6/7 using stably transformed S2 cells can also be used to produce rotavirus
      VLPs.

PMID- 20820875
TI  - Medical therapies for meningiomas.
AB  - Meningiomas are the most common primary brain tumor in adults. Although the
      majority of these tumors can be effectively treated with surgery and radiation
      therapy, an important subset of patients have inoperable tumors, or develop
      recurrent disease after surgery and radiotherapy, and require some form of
      medical therapy. There are increasing numbers of studies evaluating various
      medical therapies but the results remain disappointing. Chemotherapies and
      hormonal therapies have been generally ineffective, although somatostatin
      analogues may have therapeutic potential. There is also increasing interest in
      targeted molecular therapies. Agents inhibiting platelet derived growth factor
      receptors and epidermal growth factor receptors have shown little efficacy, but
      molecular agents inhibiting vascular endothelial growth factor receptors appear
      to have some promise. As with other tumors, advances in the medical therapies for
      meningiomas will require improved understanding of the molecular pathogenesis of
      these tumors, more predictive preclinical models, and efficient mechanisms for
      conducting clinical trials, given the small population of eligible patients.

PMID- 20820878
TI  - Lactoferrin promotes hyaluronan synthesis in human dermal fibroblasts.
AB  - Bovine lactoferrin (BLF) enhanced production of hyaluronan in normal human dermal
      fibroblasts. The elevation of hyaluronan was accompanied by elevation of HAS2
      (hyaluronan synthase 2) mRNA transcription and HAS2 protein expression. The
      promoting effect of BLF was not observed for HAS1. In addition, COL1A1
      transcription and collagen synthesis were enhanced by BLF. These observations
      suggest that BLF promotes wound healing by increasing hyaluronan and type-I
      collagen synthesis.

PMID- 20820879
TI  - Expression of human apolipoprotein A-I in Nicotiana tabacum.
AB  - Several transgenic tobacco lines expressing human apolipoprotein A-I (ApoA-I)
      were obtained. Western blot analyses indicated the expression of the recombinant
      protein in plant organs at various stages of development, including senescent
      leaves. A cell line expressing human ApoA-I was established from a T(1)
      transgenic plant. Recombinant ApoA-I was isolated either from extracts of
      transgenic leaves and from the culture medium of transgenic cells using an
      antibody-based one-step procedure.

PMID- 20820880
TI  - Improvement of the CuZn-superoxide dismutase enzyme activity and stability as a
      therapeutic agent by modification with polysialic acids.
AB  - The optimal process for the polysialylation reaction was as follows:
      polysialicacid (PSA) was activated by periodate oxidation, then coupled to CuZn
      superoxide dismutase (SOD) with a PSA:SOD molar ratio of 40:1 for 24 h. The
      resulting polysialylated protein contained 3.9 +/- 0.3 mol PSA per mol SOD. SDS
      PAGE and atomic force microscopy revealed that the molecular weight of
      polysialylated SOD was about 90-100 kDa. The average size was 10-15 nm, about
      four-fold of the native enzyme. Compared to the native enzyme, the activity and
      stability of the polysialylated SOD, as well as resistance to heat, acid, alkali
      and proteases present in human digestive system such as pepsin and trypsin, were
      improved significantly as therapeutic agent.

PMID- 20820882
TI  - Analysis of genetic diversity in flowering dogwood natural stands using
      microsatellites: the effects of dogwood anthracnose.
AB  - Flowering dogwood (Cornus florida L.) populations recently have experienced
      severe declines caused by dogwood anthracnose. Mortality has ranged from 48 to
      98%, raising the concern that genetic diversity has been reduced significantly.
      Microsatellite data were used to evaluate the level and distribution of genetic
      variation throughout much of the native range of the tree. Genetic variation in
      areas affected by anthracnose was as high as or higher than areas without die
      offs. We found evidence of four widespread, spatially contiguous genetic
      clusters. However, there was little relationship between geographic distance and
      genetic difference. These observations suggest that high dispersal rates and
      large effective population sizes have so far prevented rapid loss of genetic
      diversity. The effects of anthracnose on demography and community structure are
      likely to be far more consequential than short-term genetic effects.

PMID- 20820881
TI  - Both the stimulation and inhibition of root hair growth induced by extracellular
      nucleotides in Arabidopsis are mediated by nitric oxide and reactive oxygen
      species.
AB  - Root hairs secrete ATP as they grow, and extracellular ATP and ADP can trigger
      signaling pathways that regulate plant cell growth. In several plant tissues the
      level of extracellular nucleotides is limited in part by ectoapyrases (ecto
      NTPDases), and the growth of these tissues is strongly influenced by their level
      of ectoapyrase expression. Both chemical inhibition of ectoapyrase activity and
      suppression of the expression of two ectoapyrase enzymes by RNAi in Arabidopsis
      resulted in inhibition of root hair growth. As assayed by a dose-response curve,
      different concentrations of the poorly hydrolysable nucleotides, ATPgammaS and
      ADPbetaS, could either stimulate (at 7.5-25 MUM) or inhibit (at >= 150 MUM) the
      growth rate of root hairs in less than an hour. Equal amounts of AMPS, used as a
      control, had no effect on root hair growth. Root hairs of nia1nia2 mutants, which
      are suppressed in nitric oxide (NO) production, and of atrbohD/F mutants, which
      are suppressed in the production of H(2)O(2), did not show growth responses to
      applied nucleotides, indicating that the growth changes induced by these
      nucleotides in wild-type plants were likely transduced via NO and H(2)O(2)
      signals. Consistent with this interpretation, treatment of root hairs with
      different concentrations of ATPgammaS induced different accumulations of NO and
      H(2)O(2) in root hair tips. Two mammalian purinoceptor antagonists also blocked
      the growth responses induced by extracellular nucleotides, suggesting that they
      were initiated by a receptor-based mechanism.

PMID- 20820883
TI  - Modification of cell surface properties of Pseudomonas alcaligenes S22 during
      hydrocarbon biodegradation.
AB  - Biodegradation of water insoluble hydrocarbons can be significantly increased by
      the addition of natural surfactants one. Very promising option is the use of
      saponins. The obtained results indicated that in this system, after 21 days, 92%
      biodegradation of diesel oil could be achieved using Pseudomonas alcaligenes. No
      positive effect on the biodegradation process was observed using synthetic
      surfactant Triton X-100. The kind of carbon source influences the cell surface
      properties of microorganisms. Modification of the surface cell could be observed
      by control of the sedimentation profile. This analytical method is a new approach
      in microbiological analysis.

PMID- 20820884
TI  - Evaluation of ozone for preventing fungal influenced corrosion of reinforced
      concrete bridges over the River Nile, Egypt.
AB  - Fungal influenced corrosion (FIC) of some corroded sites in three selected
      bridges [Embaba bridge (E-bridge), Kasr al-Nile-bridge (K-bridge) and University
      bridge (U-bridge)] located over the River Nile in Egypt were investigated. Six
      fungal species, belong to 12 fungal genera, were isolated from the corroded
      reinforced concrete of the three tested bridges. Fourier transform infrared
      spectroscopy (FTIR) was screened for the most dominant fungal species (Fusarium
      oxysporium) which showed in all tested bridges that indicated the presence of
      amine group accompanied with polysaccharides contents. FIC of the most
      deteriorated bridge (K-bridge) was documented with FTIR. The association of
      fungal spores with corrosion products was recorded with scanning electron
      microscope (SEM). Evaluation of ozone for preventing FIC of the K-bridge was
      carried out by recording the corrosion rate and the corresponding inhibition
      efficiency (IE%). No mycelial growth with 100% IE was observed at 3 ppm ozone
      concentration after 120 min exposure time. With longer duration of ozone
      exposure, the membrane permeability of F. oxysporium was compromised as indicated
      by protein and nucleic acid leakages accompanied with lipid and tryptophan
      oxidation. The total intracellular and extracellular proteins of F. oxysporium
      were run on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)
      indicated the increasing of the supernatant protein on the expense of the
      cellular protein bands with extending ozone exposure time (0-80 min).

PMID- 20820885
TI  - ENPP1/PC-1 K121Q polymorphism and genetic susceptibility to type 2 diabetes in
      North Indians.
AB  - Genetic susceptibility may be responsible for high prevalence of type 2 diabetes
      worldwide. A common missense single nucleotide polymorphism, K121Q in the
      ectoenzyme nucleotide pyrophosphate phosphodiesterase (ENPP1) gene, has recently
      been associated with type 2 diabetes in Italian, South Indian, and American
      populations. The objective of this study was to investigate the possible role of
      K121Q polymorphism in ENPP1 gene with type 2 diabetes in North Indians. The
      genotype of the ENPP1/PC-1 K121Q polymorphism was determined using polymerase
      chain reaction-restriction fragment length polymorphism analysis for 328 T2DM
      patients and 326 non-diabetic participants. Anthropometric and clinical
      characteristics (Body mass index (BMI), glucose, total cholesterol, triglyceride,
      high-density lipoprotein cholesterol (HDL), Creatinine, HbA1c, and insulin
      levels) were measured using standard protocols. Their Chi-square analyses were
      used to test the significance differences in genotypic and allelic frequencies.
      Association studies were undertaken using the t test and logistic regression
      analyses. Our results revealed there was no significant difference in the
      genotypic distribution between T2DM patients and control subjects. The KK and KQ
      genotype frequencies were similar in T2DM cases and controls (60.7 and 39.3% in
      T2DM and 59.8 and 40.2% in controls). No subjects with the QQ genotype were
      found. Binary logistic regression analysis of data did not show any association
      of K121Q polymorphism with type 2 diabetes (OR; 0.97, 95% CI; 0.7-1.32, P =
      0.82). No significant correlation among the BMI, WHR, BP, TG, TC, HDL-C, LDL-C,
      Glucose, HbA1c, Creatinine, and insulin indices (HOMA-IR) was observed in the
      individuals carrying KK and KQ genotypes. In conclusion, our results showed that
      ENPP1/PC-1 K121Q polymorphism is not associated with type 2 diabetes and related
      quantitative metabolic traits in North Indian Punjabi population.

PMID- 20820886
TI  - In vitro and in vivo behavior of ketoprofen intercalated into layered double
      hydroxides.
AB  - Ketoprofen (Ket) was intercalated into layered double hydroxides (ZnAlLDH and
      MgAlLDH) using the ionic exchange method. The drug intercalation was confirmed by
      X-ray diffraction (XRD) and FTIR spectroscopy. Ket release from the inorganic
      matrix was studied at pH 7.4 in continuous regime with a flow rate of 0.5 and
      respectively 1.0 ml/min. The kinetical data were interpreted using the Ritger and
      Peppas model. The data prove that the release kinetics and mechanism depend on
      the eluent flow rate. Quantification of gastric tolerance shows that the
      ulcerogenic effect of the intercalated drug is lower than the one of the raw Ket.
      The antinociceptive effect of both formulations was studied by the hot-plate
      method performed on mice. The MgAlLDH_Ket formulation shows a tendency towards a
      stronger antinociceptive effect than its ZnAlLDH_Ket counterpart during the 210
      min recorded period.

PMID- 20820887
TI  - Expression of ladybird-like homeobox 2 (LBX2) during ovarian development and
      folliculogenesis in the mouse.
AB  - The Ladybird-like homeobox gene 2 (Lbx2) belongs to the homeodomain-containing
      family of transcription factor that are known to play crucial role in various
      developmental processes. During early mouse embryogenesis, Lbx2 was shown to be
      expressed in the developing eye, brain and urogenital system. Although Lbx2 was
      detected in the testis and epididymis throughout development, no data was
      available regarding its expression in the female gonad. Here we have determined
      Lbx2 expression throughout mouse ovarian development by in situ hybridization. In
      contrast to the strong expression in the male fetal gonad, no Lbx2 signal could
      be detected in the fetal ovary. Soon after birth, however, Lbx2 expression was
      detected at different levels in various ovarian compartments (oocyte, granulosa
      cells, theca cells) where its expression was highly dynamic depending on the
      stage of follicular maturation. Our data would be consistent with a role for LBX2
      in ovarian maturation and folliculogenesis.

PMID- 20820888
TI  - Carbonic anhydrases in the mouse harderian gland.
AB  - The harderian gland is located within the orbit of the eye of most terrestrial
      vertebrates. It is especially noticeable in rodents, in which it synthesises
      lipids, porphyrins, and indoles. Various functions have been ascribed to the
      harderian gland, such as lubrication of the eyes, a site of immune response, and
      a source of growth factors. Carbonic anhydrases (CAs) are zinc-containing
      metalloenzymes that catalyse the reaction CO2 + H2O <--> H+ + HCO3. They are
      involved in the adjustment of pH in the secretions of different glands. Thirteen
      enzymatically active isozymes have been described in the mammalian alpha-CA
      family. Here, we first investigated the mRNA expression of all 13 active CAs in
      the mouse harderian gland by quantitative real-time PCR. Nine CA mRNAs were
      detectable in the gland. Car5b and Car13 showed the highest signals. Car4, Car6,
      and Car12 showed moderate expression levels, whereas Car2, Car3, Car7, and Car15
      mRNAs were barely within the detection limits. Immunohistochemical staining was
      performed to study the expression of Car2, Car4, Car5b, Car12, and Car13 at the
      protein level. The epithelial cells were intensively stained for CAVB, whereas
      only weak signal was detected for CAXIII. Positive signals for CAIV and CAXII
      were observed in the capillary endothelial cells and the basolateral plasma
      membrane of the epithelial cells, respectively. This study provides an expression
      profile of all CAs in the mouse harderian gland. These results should improve our
      understanding of the distribution of CA isozymes and their potential roles in the
      function of harderian gland. The high expression of mitochondrial CAVB at both
      mRNA and protein levels suggests a role in lipid synthesis, a key physiological
      process of the harderian gland.

PMID- 20820889
TI  - Methyl 6-methylsalicylate: a female-produced pheromone component of the
      parasitoid wasp Spalangia endius.
AB  - Sex-pheromone-related behavior and chemistry were studied in the wasp Spalangia
      endius Walker (Hymenoptera: Pteromalidae), a pupal parasitoid of the house fly,
      Musca domestica L. (Diptera: Muscidae). Males responded behaviorally to female
      extracts by arrestment, whereas females did not arrest to male extracts. In a
      comparison of male and female extracts by gas chromatography-mass spectrometry
      (GC-MS), two female-specific compounds were found. One was identified as methyl 6
      methylsalicylate (gas chromatographic retention time and mass spectrum versus an
      authentic standard), but the chemical structure of the second compound is still
      unknown. Male antennae were sensitive to both compounds in electrophysiological
      tests (GC-EAD). Males responded behaviorally to methyl 6-methylsalicylate by
      arrestment, but did not arrest to the second compound. Methyl 6-methylsalicylate
      has been reported previously from some ant and beetle species, but never from the
      Pteromalidae. Chemical analysis of the extracts and the male behavioral results
      are consistent with the hypothesis that methyl 6-methylsalicylate functions as a
      female-emitted pheromone component at short range, but the exact role of both
      compounds in intersexual interactions in S. endius remains to be determined.

PMID- 20820890
TI  - Molecular, biochemical, and organismal analyses of tomato plants simultaneously
      attacked by herbivores from two feeding guilds.
AB  - Previous work identified aphids and caterpillars as having distinct effects on
      plant responses to herbivory. We sought to decipher these interactions across
      different levels of biological organization, i.e., molecular, biochemical, and
      organismal, with tomato plants either damaged by one 3rd-instar beet armyworm
      caterpillar (Spodoptera exigua), damaged by 40 adult potato aphids (Macrosiphum
      euphorbiae), simultaneous damaged by both herbivores, or left undamaged
      (controls). After placing insects on plants, plants were transferred to a growth
      chamber for 5 d to induce a systemic response. Subsequently, individual leaflets
      from non-damaged parts of plants were excised and used for gene expression
      analysis (microarrays and quantitative real-time PCR), C/N analysis, total
      protein analysis, proteinase inhibitor (PI) analysis, and for performance assays.
      At the molecular level, caterpillars up-regulated 56 and down-regulated 29 genes
      systemically, while aphids up-regulated 93 and down-regulated 146 genes, compared
      to controls. Although aphids induced more genes than caterpillars, the magnitude
      of caterpillar-induced gene accumulation, particularly for those associated with
      plant defenses, was often greater. In dual-damaged plants, aphids suppressed 27%
      of the genes regulated by caterpillars, while caterpillars suppressed 66% of the
      genes regulated by aphids. At the biochemical level, caterpillars induced three
      fold higher PI activity compared to controls, while aphids had no effects on PIs
      either alone or when paired with caterpillars. Aphid feeding alone reduced the
      foliar C/N ratio, but not when caterpillars also fed on the plants. Aphid and
      caterpillar feeding alone had no effect on the amount of protein in systemic
      leaves; however, both herbivores feeding on the plant reduced the amount of
      protein compared to aphid-damaged plants. At the organismal level, S. exigua
      neonate performance was negatively affected by prior caterpillar feeding,
      regardless of whether aphids were present or absent. This study highlights areas
      of concordance and disjunction between molecular, biochemical, and organismal
      measures of induced plant resistance when plants are attacked by multiple
      herbivores. In general, our data produced consistent results when considering
      each herbivore separately but not when considering them together.

PMID- 20820891
TI  - Parasitoids modify their oviposition behavior according to the sexual origin of
      conspecific cuticular hydrocarbon traces.
AB  - Hydrocarbons play a crucial role in insect behavior in general and in sexual
      recognition in particular. Parasitoids often modify their oviposition behavior
      according to hydrocarbons left by conspecifics on the reproductive patch, such as
      oviposition markers left by females after oviposition, or cuticular hydrocarbon
      (CHC) traces left by individuals by walking or rubbing. This study determined
      whether Eupelmus vuilleti females are able to distinguish CHCs left by male or
      female conspecifics on seeds. The results show that the cuticular profile of E.
      vuilleti differs according to its gender, and that females are able to detect the
      sexual origin of these CHCs. Moreover, they adjust their oviposition behavior
      according to the nature of these traces. Although females lay fewer eggs on hosts
      when confronted with female CHCs, they lay more daughters when confronted with
      male CHCs, thus changing the sex ratio.

PMID- 20820893
TI  - The oxoglutarate/malate carrier of rat brain mitochondria operates by a uniport
      exchange mechanism.
AB  - Here, the oxoglutarate carrier, already isolated from various sources and
      described in the literature, has been purified from rat brain and reconstituted
      in proteoliposomes for an accurate kinetic study. The rate of uptake of labelled
      oxoglutarate and malate has been measured in various conditions, essentially in
      double substrate experiments. The data so obtained fit the hypothesis that the
      carrier operates by a uniport-exchange mechanism and provide significant values
      for the kinetic constants and the equilibrium constants implied in the process.
      Their analysis leads to the conclusion that the carrier is maximally efficient in
      the exchange between external malate and internal oxoglutarate, as required by
      the malate/aspartate shuttle, which should be the main role of the oxoglutarate
      carrier in brain mitochondria.

PMID- 20820894
TI  - Maternal acceptance and adolescents' emotional communication: a longitudinal
      study.
AB  - With substantive evidence suggesting that adolescents' disclosure is likely a
      protective factor against problem behaviors, as well as evidence that many
      adolescents will go to great lengths to avoid sharing information with parents,
      one may conclude that parents' face a formidable task. Previous studies have
      identified parental acceptance as a concurrent correlate of adolescents'
      behavioral disclosure, but have neglected to investigate potential ways that
      parents could encourage their adolescents to feel comfortable disclosing
      emotional information. The present study extends the literature by using a
      longitudinal, multi-method, multi-reporter design to examine whether maternal
      acceptance is predictive of emotional disclosure over time among a
      racially/socioeconomically diverse sample of 184 adolescents (53% female).
      Results indicate that adolescents who perceive their mothers as high in
      acceptance during early adolescence exhibit greater relative increases in both
      self-reported emotional communication and observed emotional disclosure to their
      mothers 3 years later. Interestingly, mothers' perceptions of their own
      acceptance does not provide any additional predictive value. These findings
      support the notion that adolescents' emotional disclosure is an ongoing process
      that can be fostered in early adolescence, and emphasize the importance of
      considering adolescents' perceptions of the relationship to successfully do so.

PMID- 20820895
TI  - Associations of parental and peer characteristics with adolescents' social
      dominance orientation.
AB  - Studies with adults of social dominance orientation (SDO), a preference for
      inequality among social groups, have found correlations with various prejudices
      and support for discriminatory practices. This study explores the construct among
      adolescents at an age when they are beginning to recognize the social groups in
      their environment, particularly adolescent crowds. The relationship of SDO and
      perceptions of parents' responsiveness and demandingness were also investigated.
      Subjects were in grades 9-12 (N = 516, 53% female, 96% White). Mother's and
      father's responsiveness significantly predicted adolescent's SDO scores, with
      greater perceived responsiveness associated with lower SDO. To analyze the
      multiple crowd memberships of the 76% belonging to more than one crowd, two-step
      cluster analysis was used to identify patterns, resulting in 8 clusters of
      distinct, heterogeneous composition. SDO differed significantly among males in
      different clusters, but not females. The importance of membership was positively
      associated with SDO among high-status crowds and negatively associated with SDO
      among the academic and normal crowds. The findings have implications for
      prejudices that may be developing in adolescence and indicate a need for further
      research into the social context of SDO and its development.

PMID- 20820897
TI  - Views of older Native American adults in colonial New England.
AB  - This study examines the perceptions and treatment of older Native American adults
      in colonial New England (1620-1783). Social scientists have found that varying
      degrees of persistence and change have historically characterized Indian
      attitudes toward older adults in communities located in the central and western
      United States. In regards to northeastern North America, historians have learned
      that, during the colonial period, older Europeans dealt with a variety of
      attitudes and experiences. This study examines how English colonists and Indians
      viewed and treated older Native American adults in part of northeastern North
      America. Available documents show that while indigenous persons valued and
      respected older adults before and throughout the colonial period, English
      colonists, particularly among the clergy, held more mixed views of older Native
      Americans, including notions that they were frail and stubborn.

PMID- 20820896
TI  - Feelings of abandonment and quality of life among older persons in rural
      northeast Thailand.
AB  - The purpose of this study was to determine the extent to which older persons in
      rural Northeast Thailand felt abandoned by the emigration of their children and
      the impact this may have on their quality of life. A cross sectional survey,
      consisting of 113 questions including the 26-item WHOQOL-BREF and the 24-item
      WHOQOL-OLD was administered to 212 participants. Participants ranged in age from
      60 to 107 with a mean age of 71. While only 9% were found to live alone, 20%
      stated that they felt abandoned to some degree. A one-way between groups MANOVA
      was conducted to determine if those who felt abandoned differed from those who
      did not on a single-item question of Overall QOL and the total scores for the
      WHOQOL-BREF and WHOQOL-OLD. A statistically significant difference was found
      between the groups on the combined dependent variable [F (3, 208) = 4.75, p =
      .003; Wilks' Lambda = .94]. When the results for each of the dependent variables
      were considered separately, statistically significant differences were found on
      the WHOQOL-BREF [F (1, 210) = 13.61, p < .001] and the WHOQOL-OLD [F (1, 210) =
      9.85, p = .001] only.

PMID- 20820898
TI  - Does greater low frequency EEG activity in normal immaturity and in children with
      epilepsy arise in the same neuronal network?
AB  - Greater low frequency power (<8 Hz) in the electroencephalogram (EEG) at rest is
      normal in the immature developing brain of children when compared to adults.
      Children with epilepsy also have greater low frequency interictal resting EEG
      activity. Whether these power elevations reflect brain immaturity due to a
      developmental lag or the underlying epileptic pathophysiology is unclear. The
      present study addresses this question by analyzing spectral EEG topographies and
      sources for normally developing children and children with epilepsy. We first
      compared the resting EEG of healthy children to that of healthy adults to isolate
      effects related to normal brain immaturity. Next, we compared the EEG from 10
      children with generalized cryptogenic epilepsy to the EEG of 24 healthy children
      to isolate effects related to epilepsy. Spectral analysis revealed that global
      low (delta: 1-3 Hz, theta: 4-7 Hz), medium (alpha: 8-12 Hz) and high (beta: 13-25
      Hz) frequency EEG activity was greater in children without epilepsy compared to
      adults, and even further elevated for children with epilepsy. Topographical and
      tomographic EEG analyses showed that normal immaturity corresponded to greater
      delta and theta activity at fronto-central scalp and brain regions, respectively.
      In contrast, the epilepsy-related activity elevations were predominantly in the
      alpha band at parieto-occipital electrodes and brain regions, respectively. We
      conclude that lower frequency activity can be a sign of normal brain immaturity
      or brain pathology depending on the specific topography and frequency of the
      oscillating neuronal network.

PMID- 20820899
TI  - Breast cancer screening interventions in selected counties across US regions.
AB  - OBJECTIVES: To determine the types of, and the populations targeted by
      interventions implemented to increase breast cancer screening rates in counties
      with large African American populations across different US regions. METHODS: A
      brief questionnaire was administered by e-mail to county representatives from 33
      states from October 2008 through March 2009. Responses were obtained from 33% of
      203 targeted counties. RESULTS: Most counties (>80%) reported interventions for
      African American women and for women with low income. Women were exposed to
      different kinds of interventions depending on where they lived. Most counties in
      the Northeast (93%), Southwest (82%), and Midwest (100%) implemented
      interventions that provided free or low cost mammograms. Counties in the
      Southeast (83%) were more likely to report education interventions. Counties from
      the Southwest reported using a variety of interventions to encourage breast
      cancer screening. CONCLUSION: In this selected group of counties, different types
      of interventions were used to increase breast cancer screening in minority and
      disadvantaged women. Interventions implemented were similar to those shown in the
      literature to be effective in increasing screening rates in specific populations.
      Future research should examine the use of screening interventions in a larger
      sample of US counties.

PMID- 20820900
TI  - Pooled analyses of 13 prospective cohort studies on folate intake and colon
      cancer.
AB  - OBJECTIVE: Studies of folate intake and colorectal cancer risk have been
      inconsistent. We examined the relation with colon cancer risk in a series of 13
      prospective studies. METHODS: Study- and sex-specific relative risks (RRs) were
      estimated from the primary data using Cox proportional hazards models and then
      pooled using a random-effects model. RESULTS: Among 725,134 participants, 5,720
      incident colon cancers were diagnosed during follow-up. The pooled multivariate
      RRs (95% confidence interval [CI]) comparing the highest vs. lowest quintile of
      intake were 0.92 (95% CI 0.84-1.00, p-value, test for between-studies
      heterogeneity = 0.85) for dietary folate and 0.85 (95% CI 0.77-0.95, p-value,
      test for between-studies heterogeneity = 0.42) for total folate. Results for
      total folate intake were similar in analyses using absolute intake cutpoints
      (pooled multivariate RR = 0.87, 95% CI 0.78-0.98, comparing >= 560 mcg/days vs.
      <240 mcg/days, p-value, test for trend = 0.009). When analyzed as a continuous
      variable, a 2% risk reduction (95% CI 0-3%) was estimated for every 100 MUg/day
      increase in total folate intake. CONCLUSION: These data support the hypothesis
      that higher folate intake is modestly associated with reduced risk of colon
      cancer.

PMID- 20820902
TI  - Cognitive deficits and positively biased self-perceptions in children with ADHD.
AB  - This study examined the relation between cognitive deficits and positive bias in
      a sample of 272 children with and without Attention Deficit Hyperactivity
      Disorder (ADHD; 7-12 years old). Results indicated that children with ADHD with
      and without biased self-perceptions exhibit differences in specific cognitive
      deficits (executive processes, working memory, broad attention, and cognitive
      fluency) compared to each other and to control children. Further, specific
      cognitive deficits emerged as partial mediators of the relation between ADHD
      diagnostic status and positive bias. Interestingly, some differences in results
      emerged based on the domain considered (academic, social, behavioral competence).
      Results lend initial support to the role of cognitive deficits in the positive
      bias of some children with ADHD. Implications for future research and
      intervention are discussed.

PMID- 20820901
TI  - Intakes of vitamins A, C, and E and use of multiple vitamin supplements and risk
      of colon cancer: a pooled analysis of prospective cohort studies.
AB  - OBJECTIVE: To evaluate the associations between intakes of vitamins A, C, and E
      and risk of colon cancer. METHODS: Using the primary data from 13 cohort studies,
      we estimated study- and sex-specific relative risks (RR) with Cox proportional
      hazards models and subsequently pooled RRs using a random effects model. RESULTS:
      Among 676,141 men and women, 5,454 colon cancer cases were identified (7-20 years
      of follow-up across studies). Vitamin A, C, and E intakes from food only were not
      associated with colon cancer risk. For intakes from food and supplements (total),
      the pooled multivariate RRs (95% CI) were 0.88 (0.76-1.02, >4,000 vs. <= 1,000
      MUg/day) for vitamin A, 0.81 (0.71-0.92, >600 vs. <= 100 mg/day) for vitamin C,
      and 0.78 (0.66-0.92, > 200 vs. <= 6 mg/day) for vitamin E. Adjustment for total
      folate intake attenuated these associations, but the inverse associations with
      vitamins C and E remained significant. Multivitamin use was significantly
      inversely associated with colon cancer risk (RR = 0.88, 95% CI: 0.81-0.96).
      CONCLUSIONS: Modest inverse associations with vitamin C and E intakes may be due
      to high correlations with folate intake, which had a similar inverse association
      with colon cancer. An inverse association with multivitamin use, a major source
      of folate and other vitamins, deserves further study.

PMID- 20820903
TI  - Analysis of genetic diversity of chukar partridge (Alectoris chukar) populations
      in Khorasan-e-Razavi province of Iran by RAPD-PCR.
AB  - RAPD markers were used to investigate population genetic parameters of an
      endangered partridge, Alectoris chukar, in four areas of Iran, as a part of a
      genetic conservation program. The aim of this study was to analyze the genetic
      similarity among these populations. Blood samples from 75 birds were used for DNA
      extraction and RAPD-PCR analysis of 67 loci, with 28 polymorphic bands (41.79%).
      The populations of Kalat-e-Nader and Mashhad were found to be closely related, as
      were the Torbat-e-Jaam and the Quchan populations. Mean heterozygosity for all
      populations was 0.4405 +/- 0.0755. The results indicate that chukar partridge
      genetic diversity in Khorasan-e-Razavi province is sufficient and the amount of
      gene flow among populations is acceptable.

PMID- 20820904
TI  - PON1 55 and 192 gene polymorphisms in type 2 diabetes mellitus patients in a
      Turkish population.
AB  - Diabetes mellitus is a multifactorial metabolic disease, caused by the complete
      or relative absence of insulin hormone, which results in the deterioration of
      carbohydrate, protein, and lipid metabolism. The PON1 55 and 192 polymorphisms
      have been reported to be associated with type 2 diabetes and its complications.
      In this study, the involvement of the PON1 55 and 192 polymorphisms and
      paraoxonase enzyme activity in diabetic complications was assessed. The MM and QQ
      genotypes were the most frequent in complications of type 2 diabetes in both of
      the polymorphisms. PON enzyme activity was lower in the type 2 diabetes group
      with respect to the control group. Regarding both genotypes and enzyme activity,
      correlations were found between the PON1 55 and 192 genotypes and diabetic
      complications. This study thus helps to outline a genotype-phenotype relation for
      the PON1 gene in a Turkish population.

PMID- 20820905
TI  - Genetic diversity of the melanocortin 4 receptor (MC4R) gene and its association
      with slaughter traits in the Landes goose.
AB  - Melanocortin 4 receptor (MC4R) plays a crucial part in regulating feeding
      behavior in humans and rodents. We detected two single nucleotide polymorphisms
      (SNPs; c.108G -> A and c.627C -> T) in the goose MC4R gene and genotyped 94
      Landes geese for association analysis with several carcass traits. Significant
      associations (P < 0.05) were obtained for c.108G -> A with carcass weight, breast
      muscle percentage, and leg muscle percentage, and for c.627C -> T with body
      weight, carcass weight, semi-eviscerated weight, and eviscerated weight. We re
      constructed haplotypes based on the two SNPs and analyzed diplotypes in
      association with carcass traits, obtaining significant associations with several
      of the traits. These results suggest that polymorphisms in the MC4R gene could
      have effects on carcass traits in Landes geese. More study is required to confirm
      these results.

PMID- 20820906
TI  - The origin of the white Roman goose.
AB  - In order to avoid interference from nuclear copies of mitochondrial DNA (numts),
      mtDNA of the white Roman goose (domestic goose) was extracted from liver
      mitochondria. The mtDNA control region was amplified using a long PCR strategy
      and then sequenced. Neighbor-joining, maximum parsimony, and maximum-likelihood
      approaches were implemented using the 1,177 bp mtDNA control region sequences to
      compute the phylogenetic relationships of the domestic goose with other geese.
      The resulting identity values for the white Roman geese were 99.1% (1,166/1,177)
      with western graylag geese and 98.8% (1,163/1,177) with eastern graylag geese. In
      molecular phylogenetic trees, the white Roman goose was grouped in the graylag
      lineage, indicating that the white Roman goose came from the graylag goose (Anser
      anser). Thus, the scientific name of the white Roman goose should be Anser anser
      'White Roman.'

PMID- 20820907
TI  - Combined treatment with bevacizumab and standard chemotherapy restores abnormal
      immune parameters in advanced colorectal cancer patients.
AB  - BACKGROUND: Bevacizumab, a monoclonal antibody (mAb) targeting vascular
      endothelial growth factor (VEGF), has produced promising results when combined
      with chemotherapy in the treatment of advanced colorectal cancer (CRC). The aim
      of the present study was to define the immunological profile of metastatic CRC
      patients at baseline and following chemotherapy with either irinotecan/5
      fluorouracil/leucovorin (IFL) alone or IFL in combination with.bevacizumab (B
      IFL). METHODS: Peripheral blood mononuclear cells (PBMCs) obtained from healthy
      donors (HD) (n = 20) and patients (n = 40) were tested for T-cell proliferation
      in the autologous mixed lymphocyte reaction (auto-MLR), and cytokine production
      following stimulation with anti-CD3 mAb. RESULTS: PBMCs obtained from CRC
      patients prior to treatment exhibited lower auto-MLR responses and low production
      of IL-2, IFN-gamma, IL-12 and IL-18 cytokines, whereas IL-4 and IL-10 cytokines
      were increased as compared to HD (p < 0.001, for all parameters) following in
      vitro stimulation with anti-CD3 mAb. During treatment, and in particular in week
      12 of evaluation, IL-2 (p < 0.001 for both IFL and B-IFL groups), IFN-gamma (p <
      0.001 for IFL and p = 0.001 for B-IFL), IL-12 (p < 0.001 for both IFL and B-IFL)
      and IL-18 (p < 0.001 for both IFL and B-IFL) production, as well as auto-MLR
      responses increased (p < 0.001 for both IFL and B-IFL), whereas IL-4 (p < 0.001
      for IFL and p = 0.001 for B-IFL) and IL-10 [p < 0.001 for IFL and p = 0.067 (non
      significant) for B-IFL] production decreased over baseline in the two treatment
      groups, yet their respective values never reached those of HD. Moreover, IL-2,
      IFN-gamma production, and auto-MLR were higher in the B-IFL over the IFL
      treatment group (p < 0.001, p < 0.04, p < 0.001, respectively). CONCLUSION: Our
      study demonstrates that the abnormal immune parameters observed in metastatic CRC
      patients at presentation can substantially improve during treatment with either
      IFL or B-IFL. The immune parameters examined can provide a sensitive and valuable
      tool for monitoring immune function in CRC patients, and could be applied as
      surrogate markers predicting treatment-related outcome.

PMID- 20820908
TI  - Cytotoxic activity of the titanium alkoxide (OPy)(2)Ti(4AP)(2) against cancer
      colony forming cells.
AB  - A novel family of titanium alkoxides with two stable pyridinemethoxide moieties
      bound to a titanium metal center were synthesized and tested for cytotoxic
      activity on a variety of cancer cell lines using colony formation assays. One
      compound, (OPy)(2)Ti(4AP)(2), where OPy is NC(5)H(5)CH(2)O(-), and 4AP is 4
      aminophenoxide ((-)OC(6)H(5)(NH(2))-4), demonstrated increased cytotoxicity in
      breast, colon, and pancreatic cancer cell lines at 100 nanomolar levels with only
      short exposures. Further, (OPy)(2)Ti(4AP)(2) had activity in colon and pancreatic
      cancer cell lines that are usually resistant to chemotherapy. This demonstrates
      that these titanium compounds may have a role in anti-cancer therapy, similar to
      platinum-based compounds, and the (OPy)(2)Ti(4AP)(2) compound specifically
      deserves further investigation as an anti-cancer agent in chemo-resistant solid
      tumors.

PMID- 20820909
TI  - A phase I dose-escalating study of ES-285, a marine sphingolipid-derived
      compound, with repeat dose administration in patients with advanced solid tumors.
AB  - BACKGROUND: ES-285 (Spisulosine) is a novel marine compound with antitumor
      activity in preclinical studies. A phase I study was performed in patients with
      advanced solid tumors to determine the maximum tolerated dose (MTD), establish a
      safety profile, and to evaluate pharmacokinetics and efficacy of the drug.
      PATIENTS AND METHODS: Thirty patients from two centers were treated with a three
      hour ES-285 intravenous infusion for five consecutive days, every 3 weeks. Eleven
      dose levels were explored. RESULTS: No dose-limiting toxicity (DLT) occurred from
      2 to 81 mg/m2/day. Three patients had DLT, one each at dose levels 160, 120 and
      100 mg/m2/day; all had grade 4 transaminase increases, one of whom (160
      mg/m2/day) had concomitant grade 4 hepatitis and grade 3 bilirubin elevation. The
      MTD of this regimen was not reached due to early termination of the ES-285 phase
      I program, but was considered to be 80 to 100 mg/m2/day. Other toxicities
      included mild to moderate asthenia, nausea, vomiting, anemia, lymphopenia, and
      injection site reaction. Pharmacokinetic analyses showed dose proportionality on
      Days 1 and 5, a wide distribution and a long half-life. Seven patients (five with
      colorectal cancer) had stable disease (1.2-4.1 months), lasting for more than 3
      months in three patients. CONCLUSIONS: Liver enzyme elevations were dose limiting
      for ES-285 in this administration schedule. Low antitumor activity was observed.

PMID- 20820910
TI  - Antiangiogenic and antitumor activity of LP-261, a novel oral tubulin binding
      agent, alone and in combination with bevacizumab.
AB  - LP-261 is a novel tubulin targeting anticancer agent that binds at the colchicine
      site on tubulin, inducing G2/M arrest. Screening in the NCI60 cancer cell lines
      resulted in a mean GI50 of approximately 100 nM. Here, we report the results of
      testing in multiple mouse xenograft models and angiogenesis assays, along with
      bioavailability studies. To determine the antiangiogenic activity of LP-261, both
      in vitro and ex vivo experiments were performed. Human umbilical vein endothelial
      cells (HUVECs) were incubated with LP-261 at 50 nM to 10 MUM. LP-261 was also
      tested in a rat aortic ring assay, from 20 nM to 10 MUM. Multiple mouse xenograft
      studies were performed to assess in vivo antitumor activity. LP-261 was tested as
      a single agent in colon adenocarcinoma (SW620) and prostate cancer (LNCaP and
      PC3) xenografts, evaluating several different dosing schedules. LP-261 was also
      used in combination with bevacizumab in the SW620 xenograft model. LP-261 also
      exhibited high oral bioavailability and apparent lack of efflux by intestinal
      transporters such as ABCB1. LP-261 is a very potent inhibitor of angiogenesis,
      preventing microvessel outgrowth in the rat aortic ring assay and HUVEC cell
      proliferation at nanomolar concentrations. Complete inhibition of tumor growth
      was achieved in the PC3 xenograft model and shown to be schedule dependent.
      Excellent inhibition of tumor growth in the SW620 model was observed, comparable
      with paclitaxel. Combining oral, low dose LP-261 with bevacizumab led to
      significantly improved tumor inhibition. Oral LP-261 is very effective at
      inhibiting tumor growth in multiple mouse xenograft models and is well tolerated.

PMID- 20820911
TI  - Sulfated modification and cytotoxicity of Portulaca oleracea L. polysaccharides.
AB  - A water-soluble polysaccharide (POP1) was isolated from Portulaca oleracea L.
      Four sulfated derivatives of POP1 (POP1-s1, POP1-s2, POP1-s3 and POP1-s4) were
      prepared by chlorosulfonic acid method with N,N-Dicyclohexylcarbodiimide (DCC) as
      a dehydration-condensation agent. FT-IR spectra and 13C NMR spectra indicated the
      sulfated groups had been introduced at the C-6 and C-2 positions of POP1.
      Sulfated derivatives had different degree of substitution (DS) ranging from 1.01
      to 1.81, and different weight-average molecular mass (Mw) ranging from 41.4 to
      48.5 KDa. Sulfated derivatives except POP1-s5 inhibited the growth of HepG2 cells
      and Hela cells in vitro significantly, which indicated that sulfated modification
      could enhance cytotoxicity of POP1 on tumor cells. Flow cytometric studies
      revealed that sulfated derivatives could mediate the cell-cycle arrest of Hela
      cells in the S phase.

PMID- 20820912
TI  - Evidence for impaired vagus nerve activity in heart failure.
AB  - Parasympathetic control of the heart via the vagus nerve is the primary mechanism
      that regulates beat-to-beat control of heart rate. Additionally, the vagus nerve
      exerts significant effects at the AV node, as well as effects on both atrial and
      ventricular myocardium. Vagal control is abnormal in heart failure, occurring at
      early stages of left ventricular dysfunction, and this reduced vagal function is
      associated with worse outcomes in patients following myocardial infarction and
      with heart failure. While central control mechanisms are abnormal, one of the
      primary sites of attenuated vagal control is at the level of the parasympathetic
      ganglion. It remains to be seen whether or not preventing or treating abnormal
      vagal control of the heart improves prognosis.

PMID- 20820913
TI  - Central and peripheral cytokines mediate immune-brain connectivity.
AB  - The immune system is a homeostatic system that contributes to maintain the
      constancy of the molecular and cellular components of the organism. Immune cells
      can detect the intrusion of foreign antigens or alteration of self-components and
      send information to the central nervous system (CNS) about this kind of
      perturbations, acting as a receptor sensorial organ. The brain can respond to
      such signals by emitting neuro/endocrine signals capable of affecting immune
      reactivity. Thus, the immune system, as other physiologic systems, is under brain
      control. Under disease conditions, when priorities for survival change, the
      immune system can, within defined limits, reset brain-integrated neuro-endocrine
      mechanisms in order to favour immune processes at the expenses of other
      physiologic systems. In addition, some cytokines initially conceived as immune
      products, such as IL-1 and IL-6, are also produced in the "healthy" brain by
      glial cells and even by some neurons. These and other cytokines have the capacity
      to affect synaptic plasticity acting as mediators of interactions between
      astrocytes and pre- and post-synaptic neurons that constitute what is actually
      defined as a tripartite synapse. Since the production of cytokines in the brain
      is affected by peripheral immune and central neural signals, it is conceivable
      that tripartite synapses can, in turn, serve as a relay system in immune-CNS
      communication.

PMID- 20820914
TI  - Oncogramme, a new individualized tumor response testing method: application to
      colon cancer.
AB  - Colon cancer is the second leading cause of cancer-related death in
      industrialized countries. Many anti-cancer researches are consequently performed
      and individualized tumor response testing (ITRT) methods are now used to
      individualize patient chemotherapeutic administrations. Then, a new ITRT method,
      Oncogramme, was developed for colon cancer. Colon tumor fragments from different
      patients were dissociated and seeded in a defined culture medium. Cell
      preparation process as well as culture medium allowed high cell viability and a
      good primary culture success rate. After treatment of isolated tumoral cells by
      chemotherapeutics alone or in combination, cytotoxicity was determined by cell
      death assay allowing the Oncogramme establishment, which was validated by
      statistical analysis. Indeed, significant results were obtained such as different
      profile for each patient's cells with various drugs, and variability between
      patient's cells in the response to each drug. Procedure described here to obtain
      the Oncogramme is a new, fast and technically reliable ITRT method applied to
      colon cancer. For an individualized cancer treatment use, this test should be
      further validated by a phase I clinical trial.

PMID- 20820915
TI  - Characterizing changes in kidney and renal pelvis cancer incidence from 1998 to
      2006 in the United States.
AB  - In this study, we characterize the changes in kidney and renal pelvis cancer
      (RCC) from 1998 to 2006 in the United States. The goal is to examine variations
      in stage and treatments. In addition, we explore changes in risk factors that
      have occurred over the same period. Data on over 20,000 patients diagnosed with
      RCC in National Cancer Data Base were used for the study. We investigated the
      changes in stage and treatment rates based on race, gender and age at diagnosis
      from 1998 to 2006. Changes in smoking, obesity and hypertension rates over the
      period were examined for comparison. The increase in RCC incidence rates from
      1998 to 2006 was almost entirely a result of increases in stage I. Increases for
      blacks were proportionally higher than whites. Obesity and hypertension increased
      over the period but smoking declined. In terms of treatment, there was an
      increase in surgery cases primarily for stage I. There were no significant
      differences in trends based on gender, although rates in men were 65% greater
      than in women. The mean age at diagnosis was stable for stages I-IV. There are
      increased incidences of renal tumors, particularly stage I renal cancer among
      blacks and whites from 1998 to 2006. Patients were more likely to undergo
      surgical therapy for these tumors.

PMID- 20820916
TI  - Effect of pentoxifylline on semen parameters, reproductive hormones, and seminal
      plasma antioxidant capacity in men with idiopathic infertility: a randomized
      double-blind placebo-controlled study.
AB  - OBJECTIVE: To determine the safety and efficacy of oral pentoxifylline (PTX)
      administration in improving semen parameters in infertile men with idiopathic
      OAT. PATIENTS AND METHODS: The study included 254 infertile men who underwent
      double-blind therapy with 400 mg PTX (Apotex Inc., Toronto, Canada) twice daily
      (group 1, n = 127), or similar regimen of placebo (group 2, n = 127). The study
      consisted of a 4-week screening phase, a 24-week treatment phase, and a 12-week
      treatment-free period. The effects of treatment on semen parameters, serum
      hormones including testosterone, luteinizing hormone (LH), follicle-stimulating
      hormone (FSH) and inhibin B, seminal plasma catalase-like and superoxide
      dismutase (SOD)-like activity, and acrosome reaction test were evaluated.
      RESULTS: A significant increase in sperm concentration (mean value, 26.4 +/- 4.6
      * 10(6)/ml vs. 16.2 +/- 3.4 * 10(6)/ml), sperm motility (mean value, 35.8 +/-
      4.2% vs. 26.4 +/- 2.4%), and sperm with normal morphology (mean value, 25.4 +/-
      4.3% vs. 17.4 +/- 4.2%) was observed after PTX administration when compared with
      baseline (all P = 0.001); in contrast, a subtle decreased values were observed
      after placebo (median values, 16.4 +/- 4.1 * 10(6)/ml vs. 16.7 +/- 3.6 *
      10(6)/ml, P = 0.1; 25.7 +/- 3.6% vs. 26.8 +/- 2.5%, P = 0.08; and 16.9 +/- 4.1%
      vs. 17.6 +/- 4.4%, P = 0.08, respectively). Mean SOD-like and catalase-like
      activity in the semen of PTX group was significantly greater than in the semen of
      placebo group (46.4 +/- 2.4 vs. 36.3 +/- 1.3 U/ml and 371 +/- 44 vs. 301 +/- 14
      U/ml, respectively, both P = 0.003). The acrosome reaction was observed to be
      increased in PTX group (P = 0.01). Levels of reproductive hormones were also
      affected. CONCLUSIONS: PTX administration significantly improves semen parameters
      in infertile men with idiopathic OAT.

PMID- 20820917
TI  - The correlation of extent and grade of inflammation with serum PSA levels in
      patients with IV prostatitis.
AB  - OBJECTIVES: The inflammation was categorized more profoundly, using the
      standardized histopathological classification system for chronic prostatitis of
      NIH, to determine the influence of prostatic inflammation on serum PSA levels.
      METHODS: The study included 120 patients who underwent transperineal ultrasound
      guided prostate biopsy. The patients were divided into groups using 3 grades for
      the extent, the location and the aggressiveness of prostate inflammation. The
      serum tPSA levels, fPSA levels, %fPSA, and PSAD in each group were compared.
      RESULTS: Of 120 patients, 80 with benign prostatic tissue in their biopsy
      specimens met the inclusion criteria, excluding 40 cases with prostate cancer.
      The inflammation was present in 46(57.5%) of 80 cases. The extent of inflammation
      correlated positively with the total PSA level (r = 0.6, P < 0.001), fPSA (r =
      0.5, P = 0.001) and PSAD (r = 0.6, P < 0.001). The grade of inflammation
      correlated positively with the total PSA level (r = 0.5, P < 0.001), fPSA (r =
      0.4, P = 0.008) and PSAD (r = 0.7, P < 0.001). A negative correlation was found
      between the grade of inflammation and %fPSA (r = -0.4, P = 0.013). CONCLUSIONS:
      If the elevation of serum PSA is thought to be caused by asymptomatic prostatitis
      with high aggressiveness score in BPH patients without clinical prostatitis, it
      might prevent unnecessary repeated biopsies.

PMID- 20820918
TI  - Structure and procedures of the pharmacy and therapeutic committees in Spanish
      hospitals.
AB  - OBJECTIVE: Define the structure and working procedures of the Pharmacy and
      Therapeutic Committees (P&T Committees) in Spanish hospitals. SETTING: Hospitals
      over 75 beds located in all regions of the Spanish State. METHOD: A cross
      sectional descriptive study based on the completion of a questionnaire that
      consisted of 138 questions. The participants were recruited by post, e-mail and
      telephone between November 2007 and January 2008. The Hospitals were classified
      according to their size and public or private and university or non-university
      status. MAIN OUTCOME MEASURES: They are related with the structure and
      composition of the P&T Committees, performance, drug evaluation process, working
      methods and the results of their activity. RESULTS: A total of 200 hospitals
      answered the questionnaire (response rate of 39.0% of hospitals and 57.1% of the
      beds in Spain). All the hospitals have P&T Committees, 99.5% have a Drug
      Formulary, 71.0% have a Therapeutic Interchange Programme and 91.0% have a
      document determining the mission, objectives and functions of the P&T Committee.
      Almost all hospitals (95.5%) have established a formal application for the
      inclusion of a drug in the hospital, while 80.5% have established a model for
      evaluation reports. The mean (SD) number of participants in P&T Committees was
      11.84 (3.82). The annual mean of drugs evaluated per hospital was 10.35 (7.45).
      The proportion of assessments that concludes the inclusion, rejection or deferral
      of the decision was 75.3, 21.4 and 3.2%, respectively. CONCLUSION: Spanish P&T
      Committees have a similar structure and function, a multi-disciplinary
      professional composition to carry out an important assessment activity. This
      activity is higher in large hospitals and in university hospitals. The proportion
      of the approved and rejected drugs is similar in different types of hospital. The
      Therapeutic Interchange Guidelines, the use of application models and the reports
      follow the indications of scientific collaborative groups, thus being used more
      in Spain than in other countries.

PMID- 20820919
TI  - Low-intensity pulsed ultrasound modulates shear stress induced PGHS-2 expression
      and PGE2 synthesis in MLO-Y4 osteocyte-like cells.
AB  - Fluid shear stress (SS) has been shown to be a prevailing physiological stimulus
      in the regulation of bone cell metabolism and so are the exogenous biomechanical
      forces, like ultrasound (US) and vibration. The purpose of this study is to
      elaborate the interplay of laminar fluid SS with low-intensity pulsed US in the
      regulation of prostaglandin H synthase 2 (PGHS-2) and prostaglandin E2 (PGE2).
      Murine long bone osteocyte-like (MLO-Y4) cells were exposed to various regimes of
      US (1.5 Hz, 30 mW/cm2) and SS (19 dyn/cm2) alone and sequentially. Changes in
      PGHS-2 gene expression levels were quantified at 3 and 24 h using real-time RT
      PCR. PGE2 levels in the culture media were measured using enzyme immunoassay at 3
      and 24 h. PGE2 levels significantly increased after exposure to SS for 3 and 24 h
      by 2.17+/-0.02 and 5.47+/-0.42-fold, respectively, compared to control cells. A
      20 min US treatment prior to SS significantly increased SS PGE2 levels 2.95+/
      0.18 and 2.90+/-0.50-fold at 3 and 24 h, respectively. US also significantly
      increased PGHS-2 mRNA levels in cells exposed to SS. SS caused a 2.74 +/- 0.49
      fold increase in PGHS-2 mRNA levels at 3 h and a significant 3.70+/-0.25-fold
      increase at 24 h relative to control. A 20 min US treatment caused 1.35+/-0.49
      and 2.44+/-0.82-fold increase in PGHS-2 mRNA levels in cells exposed to SS at 3
      and 24 h, respectively. These results indicate that combining US with SS may have
      a more anabolic benefit for bone tissue than either stimulus alone.

PMID- 20820920
TI  - Bioreactors for development of tissue engineered heart valves.
AB  - Millions of people worldwide are diagnosed each year with valvular heart disease,
      resulting in hundreds of thousands of valve replacement operations. Prosthetic
      valve replacements are designed to correct narrowing or backflow through the
      valvular orifice. Although commonly used, these therapies have serious
      disadvantages including morbidity associated with long-term anticoagulation and
      limited durability necessitating repeat operations. The ideal substitute would be
      widely available and technically implantable for most cardiac surgeons, have
      normal hemodynamic performance, low risk for structural degeneration, thrombo
      embolism and endocarditis, and growth potential for pediatric patients. Tissue
      engineered heart valves hold promise as a viable substitute to outperform
      existing valve replacements. An essential component to the development of tissue
      engineered heart valves is a bioreactor. It is inside the bioreactor that the
      scaffold and cells are gradually conditioned to the biochemical and mechanical
      environment of the valve to be replaced.

PMID- 20820921
TI  - Multi-factorial analytical study on real-time three-dimensional echocardiographic
      cardiac image display quality.
AB  - Although real-time three-dimensional echocardiography (RT-3DE) can display
      stereoscopic images, its acquisition and image display quality are affected by
      many factors. So, the study aimed to evaluate the importance of factors affecting
      the efficiency of RT-3DE image display quality, and establish an optimized method
      for RT-3DE examination and image processing in children. Based on the specific
      cardiac acoustic characteristics in children, 83 healthy children were studied
      and divided into five groups. Three aspects of seven factors were selected for RT
      3DE examination and analysis of orthogonal test design method, including
      acquisition windows, gain, compress, post process, smoothing, frequency fusion
      and 3D Vision. The principal effective analysis of orthogonal test design method
      and its table L(18)3(7) were used. The efficiency rate of three-dimensional image
      display quality was used as the inspection index for orthogonal test design
      method. From our findings, according to the average deviation orders of seven
      factors, the maximal average deviation was the factor of gain. The aspects with
      maximal average deviation of each factor were at via-subcostal and via-apical
      acoustic windows, 90 of gain, 60 of compress, E of post process, five of
      smoothing, F3 of frequency fusion and A to B of 3D Vision, respectively. Namely,
      the optimized method for RT-3DE examination and image displaying could be
      achieved by setting the factors. Multi-factorial analytical study on RT-3DE
      cardiac image display quality could be helpful to promote clinical application of
      RT-3DE, and be conducive to design a multi-parameter presetting of ultrasound
      system to optimize RT-3DE examination.

PMID- 20820923
TI  - One-step synthesis of chitosan-silica hybrid microspheres in a microfluidic
      device.
AB  - This article describes a simple microfluidic method to fabricate chitosan-silica
      hybrid microspheres in one step. We dissolved tetraethoxysilane (TEOS) into a
      chitosan/acetic acid aqueous solution to form a chitosan-silica sol, and then
      emulsified it in an organic phase mainly containing n-octanol and an organic base
      triotylamine (TOA) via a co-axial microfluidic device. The formed aqueous
      droplets were solidified because of the extraction of acetic acid and water to
      the organic phase. The simple method presented has the advantages of controllable
      sphere diameter, narrow size distribution and good sphericity. The porous
      structures of the microspheres were displayed by SEM images. It is found that the
      inner and surface structures can be controlled by adjusting the solidification
      reagent component. Furthermore, we chemically grafted bovine serum albumin (BSA)
      on the microspheres. The existence of silica in the chitosan spheres can enhance
      both of mechanical intensity and protein loading capacity of the microspheres.

PMID- 20820922
TI  - Impact of luminal density on plaque classification by CT coronary angiography.
AB  - Non-invasive coronary CT angiography (CCTA) has the potential to characterize the
      composition of non-calcified coronary plaques. CT-density values characterized by
      Hounsfield Units (HU) may classify non-calcified plaques as fibrous or lipid
      rich, but the luminal density caused by the applied contrast material influences
      HU in the plaques in vitro. The influence of luminal density on HU in non
      calcified plaques in vivo is unknown. Hence the purpose of this study was to test
      whether plaque characterization by CCTA in vivo depends on luminal density. Two
      CCTA-scans using two different contrast protocols were obtained from 14 male
      patients with coronary artery disease. The two contrast protocols applied
      resulted in high and low luminal density. Eleven non- calcified and 13 calcified
      plaques were identified and confirmed by intravascular ultrasound. Luminal
      attenuation differed with the two contrast protocols; 326[284;367] vs.
      118[103;134] HU (P < 0.00001). In non-calcified plaques mean HU-values was lower
      48[28;69] vs. 11[-4;25] HU (P = 0.004) with the low density protocol. As a
      consequence three out of eleven non-calcified plaques (27%) were reclassified
      from fibrous (high) to lipid rich (low). For calcified plaques a less pronounced
      but still significant difference in HU-values was found with the low luminal
      density. 770[622;919] vs. 675[496;855] HU (P = 0.02). CONCLUSION: Non-calcified
      plaques can be identified and classified by CCTA. However, the luminal density
      affects the absolute HU of both non-calcified and calcified plaques.
      Characterization and classification of non-calcified plaques by absolute CT
      values therefore requires standardization of contrast protocols.

PMID- 20820924
TI  - Sequence analysis and structural characterization of a glyceraldehyde-3-phosphate
      dehydrogenase gene from the phytopathogenic fungus Eremothecium ashbyi.
AB  - Eremothecium ashbyi is a phytopathogenic fungus infesting cotton, soybeans and
      several other plants. This highly flavinogenic fungus has been phylogenetically
      characterized, but the genetic aspects of its central metabolic and riboflavin
      biosynthetic pathways are unknown. An ORF of 996 bp was obtained from E. ashbyi
      by using degenerate primers for glyceraldehyde-3-phosphate dehydrogenase (GPD)
      through reverse transcriptase polymerase chain reaction (RT-PCR) and 5'-3' rapid
      amplification of cDNA ends (RACE-PCR). This nucleotide sequence had a high
      similarity of 88% with GPD sequence of Ashbya gossypii. The putative GPD peptide
      of 331-aa had a high similarity of 85% with the GPD sequence from other
      ascomycetes. The ORF had an unusually strong codon bias with 5 amino acids
      showing strict preference of a single codon. The theoretical molecular weight for
      the putative peptide was 35.58 kDa with an estimated pI of 5.7. A neighbor
      joining tree showed that the putative peptide from E. ashbyi displayed the
      highest similarity to GPD of A. gossypii. The gene sequence is available at the
      GenBank, accession number EU717696. Homology modeling done with Kluyveromyces
      marxianus GPD (PDB: 2I5P) as template indicated high structural similarity.

PMID- 20820925
TI  - Pre-trial beliefs in complementary and alternative medicine: whose pre-trial
      belief should be considered?
AB  - Subjective probabilities play a significant role in the assessment of evidence:
      in other words, our background knowledge, or pre-trial beliefs, cannot be set
      aside when new evidence is being evaluated. Focusing on homeopathy, this paper
      investigates the nature of pre-trial beliefs in clinical trials. It asks whether
      pre-trial beliefs of the sort normally held only by those who are sympathetic to
      homeopathy can legitimately be disregarded in those trials. The paper addresses
      several surprisingly unsuccessful attempts to provide a satisfactory
      justification for ignoring the pre-trial beliefs of the homeopathic community.
      The ensuing diagnosis of the difficulties here emphasizes that the reason the
      arguments for choosing the pre-trial beliefs of the conventional community seem
      insufficient is not the arguments per se. It is rather that there is no cogent
      argument for choosing the conventional stance which would at the same time
      rationally persuade a member of the homeopathic community. The paper concludes
      that, once we understand that this is the predicament, there is no genuine reason
      to doubt the reasoning that leads us to reject the pre-trial beliefs of the
      homeopathic community.

PMID- 20820926
TI  - Measurement properties of a multicultural weight-specific quality-of-life
      instrument for children and adolescents.
AB  - PURPOSE: To evaluate the psychometric properties of a new multicultural weight
      specific quality-of-life (QOL) measure for children and adolescents-Youth Quality
      of-Life Instrument-Weight module (YQOL-W). METHODS: Twenty-five candidate items
      were administered to 443 children and adolescents between 11 and 18 years of age,
      of whom 53% were female, 33% were white, 30% were African American and 37% were
      Mexican American. Thirty-four percent had a healthy body mass index (BMI), 20%
      were overweight and 46% were obese. RESULTS: Twenty-one of the original 25
      candidate items were retained in the final instrument. Exploratory and
      confirmatory factor analyses (CFA) resulted in a one-factor (21 items, alpha =
      0.97) and a three-factor model including a Self factor (4 items, alpha = 0.90), a
      Social factor (11 items, alpha = 0.95) and an Environment factor (5 items, alpha
      = 0.90). CFA found the three-factor model had better model fit (P < 0.05). Both
      the one-factor and three-factor scores were negatively correlated with BMI and
      the Children's Depression Inventory and positively correlated with generic
      quality of life, all at the P < 0.05 level. The 1-week test-retest intra-class
      correlation coefficients were 0.73 for Social, 0.71 for Self, 0.73 Environment
      and 0.77 for the one-factor model. CONCLUSIONS: The YQOL-W shows good reliability
      and validity for assessing weight-specific QOL in children and adolescents.

PMID- 20820927
TI  - Analysis of osteoarthritis in a mouse model of the progeroid human DNA repair
      syndrome trichothiodystrophy.
AB  - The increasing average age in developed societies is paralleled by an increase in
      the prevalence of many age-related diseases such as osteoarthritis (OA), which is
      characterized by deformation of the joint due to cartilage damage and increased
      turnover of subchondral bone. Consequently, deficiency in DNA repair, often
      associated with premature aging, may lead to increased pathology of these two
      tissues. To examine this possibility, we analyzed the bone and cartilage
      phenotype of male and female knee joints derived from 52- to 104-week-old WT
      C57Bl/6 and trichothiodystrophy (TTD) mice, who carry a defect in the nucleotide
      excision repair pathway and display many features of premature aging. Using micro
      CT, we found bone loss in all groups of 104-week-old compared to 52-week-old
      mice. Cartilage damage was mild to moderate in all mice. Surprisingly, female TTD
      mice had less cartilage damage, proteoglycan depletion, and osteophytosis
      compared to WT controls. OA severity in males did not significantly differ
      between genotypes, although TTD males had less osteophytosis. These results
      indicate that in premature aging TTD mice age-related changes in cartilage were
      not more severe compared to WT mice, in striking contrast with bone and many
      other tissues. This segmental aging character may be explained by a difference in
      vasculature and thereby oxygen load in cartilage and bone. Alternatively, a
      difference in impact of an anti-aging response, previously found to be triggered
      by accumulation of DNA damage, might help explain why female mice were protected
      from cartilage damage. These findings underline the exceptional segmental nature
      of progeroid conditions and provide an explanation for pro- and anti-aging
      features occurring in the same individual.

PMID- 20820928
TI  - The endocrine disrupting potential of sediments from the Upper Danube River
      (Germany) as revealed by in vitro bioassays and chemical analysis.
AB  - INTRODUCTION: The present study was part of a comprehensive weight-of-evidence
      approach with the goal of identifying potential causes for the declines in fish
      populations, which have been observed during the past decades in the Upper Danube
      River. METHODS: The specific goal was the investigation of the endocrine
      disrupting potential of sediment extracts from different sites along the Danube
      River. Parallel to the identification and quantification of target estrogens, two
      in vitro bioassays were employed to assess the estrogenic potential (yeast
      estrogen screen, YES) of the sediment samples and to evaluate their effects on
      the production of testosterone (T) and E2 (H295R Steroidogenesis Assay). Using a
      potency balance approach, the contribution of the measured compounds (Chem-EEQs)
      to the total endocrine activity measured by the YES (YES-EEQs) was calculated.
      RESULTS AND DISCUSSION: Of the nine sediment extracts tested five extracts
      exhibited significant estrogenic activities in the YES, which suggested the
      presence of ER agonists in these samples. The xenoestrogens nonylphenol (NP) and
      bisphenol A (BPA) and the natural estrogen estrone (E1) were detected while
      concentrations of 17beta-estradiol (E2) and ethinylestradiol (EE2) were less than
      their respective limits of quantification in all sediment extracts. A comparison
      of the measured YES-EEQs and the calculated Chem-EEQs revealed that as much as 6%
      of estrogenic activity in extracts of most sediments could be explained by two
      xeno- and one natural estrogen. Exposure of H295R cells to sediment extracts from
      four different locations in the Danube River resulted in significantly increased
      concentrations of E2, but only slight inhibition of T synthesis. Furthermore,
      application of the H295R Steroidogenesis Assay provided evidence for endocrine
      disrupting potencies in sediment samples from the Upper Danube River, some of
      which were not detectable with the YES. In conclusion, differential endocrine
      activities were associated with several sediments from the Upper Danube River.
      Further investigations will have to show whether the observed activities are of
      biological relevance with regard to declines in fish populations in the Upper
      Danube River.

PMID- 20820929
TI  - Targeting integrins in malignant glioma.
AB  - The integrin family of cell adhesion receptors is emerging as a promising target
      of anticancer therapy. AlphaVbeta3 and alphaVbeta5 integrins are overexpressed on
      both glioma cells and tumor vasculature. Cilengitide, the most advanced specific
      integrin inhibitor in oncology, has shown antitumor activity against glioma in
      early clinical trials. Durable remissions have been observed in phase I and phase
      II trials for recurrent glioblastoma (GBM) with both lower and higher doses of
      cilengitide. Pilot trials in newly diagnosed glioblastoma in conjunction with
      standard chemoradiotherapy have been encouraging. Preclinical data suggest
      synergy with concomitant chemo- and radiation therapy. A pivotal phase III study
      (CENTRIC) in newly diagnosed GBM patients is currently recruiting. This paper
      summarizes the current understanding of the role of integrins and their
      inhibition in gliomagenesis. The background and design of ongoing trials are
      outlined.

PMID- 20820931
TI  - Selection of direct transesterification as the preferred method for assay of
      fatty acid content of microalgae.
AB  - Assays for total lipid content in microalgae are usually based on the Folch or
      the Bligh and Dyer methods of solvent extraction followed by quantification
      either gravimetrically or by chromatography. Direct transesterification (DT) is a
      method of converting saponifiable lipids in situ directly to fatty acid methyl
      esters which can be quantified by gas chromatography (GC). This eliminates the
      extraction step and results in a rapid, one-step procedure applicable to small
      samples. This study compared the effectiveness of DT in quantifying the total
      fatty acid content in three species of microalgae to extraction using the Folch,
      the Bligh and Dyer and the Smedes and Askland methods, followed by
      transesterification and GC. The use of two catalysts in sequence, as well as the
      effect of reaction water content on the efficiency of DT were investigated. The
      Folch method was the most effective of the extraction methods tested, but
      comparison with DT illustrated that all extraction methods were incomplete.
      Higher levels of fatty acid in the cells were obtained with DT in comparison with
      the extraction-transesterification methods. A combination of acidic and basic
      transesterification catalysts was more effective than each individually when the
      sample contained water. The two-catalyst reaction was insensitive to water up to
      10% of total reaction volume. DT proved a convenient and more accurate method
      than the extraction techniques for quantifying total fatty acid content in
      microalgae.

PMID- 20820935
TI  - An invitation to our medical colleagues: work with us.

PMID- 20820932
TI  - Limited effect of dietary saturated fat on plasma saturated fat in the context of
      a low carbohydrate diet.
AB  - We recently showed that a hypocaloric carbohydrate restricted diet (CRD) had two
      striking effects: (1) a reduction in plasma saturated fatty acids (SFA) despite
      higher intake than a low fat diet, and (2) a decrease in inflammation despite a
      significant increase in arachidonic acid (ARA). Here we extend these findings in
      8 weight stable men who were fed two 6-week CRD (12%en carbohydrate) varying in
      quality of fat. One CRD emphasized SFA (CRD-SFA, 86 g/d SFA) and the other,
      unsaturated fat (CRD-UFA, 47 g SFA/d). All foods were provided to subjects. Both
      CRD decreased serum triacylglycerol (TAG) and insulin, and increased LDL-C
      particle size. The CRD-UFA significantly decreased plasma TAG SFA (27.48 +/- 2.89
      mol%) compared to baseline (31.06 +/- 4.26 mol%). Plasma TAG SFA, however,
      remained unchanged in the CRD-SFA (33.14 +/- 3.49 mol%) despite a doubling in SFA
      intake. Both CRD significantly reduced plasma palmitoleic acid (16:1n-7)
      indicating decreased de novo lipogenesis. CRD-SFA significantly increased plasma
      phospholipid ARA content, while CRD-UFA significantly increased EPA and DHA.
      Urine 8-iso PGF(2alpha), a free radical-catalyzed product of ARA, was
      significantly lower than baseline following CRD-UFA (-32%). There was a
      significant inverse correlation between changes in urine 8-iso PGF(2alpha) and PL
      ARA on both CRD (r = -0.82 CRD-SFA; r = -0.62 CRD-UFA). These findings are
      consistent with the concept that dietary saturated fat is efficiently metabolized
      in the presence of low carbohydrate, and that a CRD results in better
      preservation of plasma ARA.

PMID- 20820930
TI  - Neuroimmune pharmacology of neurodegenerative and mental diseases.
AB  - Neuroimmune pharmacology is a newly emerging field that intersects with
      neuroscience, immunology, and pharmacology and that is seeking avenues for
      translational research and better understanding of disease mechanisms. It focuses
      on the immunity of the central nervous system (CNS) which is greatly influenced
      by endogenous effectors, such as cytokines and neurotransmitters, and by
      exogenous substances, including therapeutic compounds, infectious pathogens, and
      drugs of abuse. In this article, we attempt to raise awareness of the pivotal
      discovery of how those mediators affect the immunity of the CNS in both
      physiological conditions and processes of certain mental illnesses, including
      psychiatric disorders, neurodegenerative diseases, and cerebral dysfunctions due
      to drugs of abuse. The abnormality in cytokine networks, neurotransmitter
      homeostasis, and other immune responses may be involved in the neuropathology
      associated with those mental illnesses, and the therapeutic effects of the
      potential treatments can be attributed, at least partially, to their
      immunomodulatory activities. However, the resulting inflammatory cytokines from
      certain treatments frequently cause psychiatric complications. In addition, the
      poor neuropathological outcomes frequently found among drug abusers with HIV-1
      infection appear to be related to the neurotoxic and immunomodulatory effects of
      the drugs used. Importantly, glial cells, especially microglia and astrocytes,
      are key players in the immunomodulatory activities in the CNS, and the
      functioning CNS is largely dependent upon the reciprocal interactions between
      neurons and glial cells. Therefore, glia-neuron interactions have become a
      critical issue for further understanding the disease mechanism. From this review,
      readers will gain insights into the new field of neuroimmune pharmacology, with a
      focus on the impacts of CNS immunity on the mental illnesses.

PMID- 20820936
TI  - Changes in eating behavior after laparoscopic adjustable gastric banding: a
      systematic review of the literature.
AB  - This systematic review evaluates the current evidence base for eating behavior
      changes after laparoscopic adjustable gastric banding (LAGB). A literature search
      from 1990 to February 2010 was conducted to identify original studies that
      assessed eating behavior in adults who have undergone LAGB. Sixteen articles (14
      separate studies) met inclusion criteria. Although strength of the evidence base
      was limited by observational study designs and methodological weaknesses, results
      suggest that positive changes in eating behavior occur after surgery, including
      reduced over-eating in response to emotional and situational cues. There is some
      evidence to suggest that uncontrolled eating behaviors persist in some
      individuals, and that this may be problematic for weight loss after surgery. Few
      studies examined the relationship between changes in eating behavior and weight
      loss; thus, optimal behavioral strategies for promoting positive weight outcomes
      remain unclear. Further interventional research addressing the inherent
      limitations of the current-evidence base is required to guide development of
      evidence-based management guidelines for LAGB in future.

PMID- 20820937
TI  - Protein intake, body composition, and protein status following bariatric surgery.
AB  - BACKGROUND: Daily protein intake recommendations have recently been proposed for
      the bariatric patient. We aimed to evaluate the accomplishment of these
      recommendations, and the influence of protein intake (PI) on fat free mass (FFM)
      and protein status changes following bariatric surgery. METHODS: We examined 101
      consecutive patients undergoing laparoscopic Roux-in-Y gastric gypass (LGBP) or
      laparoscopic sleeve gastrectomy (LSG). Based on 3-day food records, PI from food
      and supplements were quantified at 4, 8, and 12 months after surgery. The
      association between PI and body composition (bioelectrical impedance), plasma
      albumin and pre-albumin was evaluated at all study time points. RESULTS: A PI <60
      g/day was present respectively in 45%, 35%, and 37% of the cohort at 4, 8, and 12
      months after surgery (p < 0.001 relative to baseline). Despite our universal
      recommendation of protein supplementation, supplements were taken only by 63.4,
      50.5, and 33.7% of the participants at 4, 8, and 12 months. However, protein
      supplementation was effective in helping patients to achieve the daily protein
      intake goal. In linear regression analysis, male gender and weight loss, but not
      PI, were significantly associated with loss of FFM (p < 0.001). No significant
      correlation between PI and plasma albumin or pre-albumin was found. CONCLUSIONS:
      Our study underscores the value of protein supplementation for the achievement of
      the recommended daily protein intake in the bariatric patient. However, our data
      does not help to define a PI goal as critical in determining the FFM and protein
      status changes following LGBP or LSG.

PMID- 20820938
TI  - Early and mid-term outcomes of single-stage laparoscopic sleeve gastrectomy.
AB  - BACKGROUND: This is the largest single-centre series of single-stage laparoscopic
      sleeve gastrectomy (LSG) reporting on perioperative outcomes, weight loss,
      comorbidity resolution including urological outcomes and results in the super
      obese. Review of prospectively collected data for patients who underwent LSG from
      March 2007-August 2009. METHODS: There were 253 patients with a mean age of 44
      years (SD, 9) and a mean preoperative body mass index (BMI) of 50 kg/m(2) (SD,
      7). There were 17 (7%) major complications and no deaths. The mean follow-up was
      9 months. One hundred and seventy-one patients with a mean follow-up of 12 months
      had a mean postoperative weight loss of 41 kg (SD, 16) and mean excess BMI
      (meBMI) loss of 59% (SD, 22). RESULTS: One hundred fourteen patients were super
      obese (BMI, >50 kg/m(2)). The mean weight loss was 45 kg (SD, 18), and the meBMI
      lost was 49% (SD, 21). Super-obese patients experienced more complications (p =
      0.02) and lost less eBMI (49% vs. 61%; p < 0.01). Fifty-three patients (46%)
      remained morbidly obese (BMI, >40 kg/m(2)) postoperatively. Hypertension and
      diabetes improved or resolved in 73 (79%) and 73 (90%) patients, respectively.
      Stress urinary incontinence was reported preoperatively in 60 (32%) females, and
      complete resolution or improvement was reported in 54 (90%) patients.
      CONCLUSIONS: LSG provides satisfactory weight loss and resolution of
      comorbidities in the short- and medium-term with inferior, though acceptable,
      results in the super obese.

PMID- 20820939
TI  - Pregnancy after bariatric surgery: 39 pregnancies follow-up in a
      multidisciplinary team.
AB  - BACKGROUND: We investigate the outcomes of pregnancy in women who undergone
      restrictive-malabsorptive procedure at Centro da Obesidade Morbida-Hospital Sao
      Lucas (COM HSL-PUCRS), Porto Alegre, Brazil. METHODS: All pregnancies started
      after the bariatric surgery and with estimated due date until June 2008 were
      eligible for the study. Only the first pregnancy of each patient was included in
      the data analysis. Data was collected from medical records. RESULTS: Forty seven
      pregnancies were identified in 41 women. Eight of them were ineligible. There
      were 30 complete pregnancies and nine miscarriages (23%). Cesarean delivery was
      performed in 69% of the complete pregnancies. Mature infants occurred in 93.1%.
      Twelve pregnancies (30.8%) occurred in the first year after surgery. Vitamin B12
      was low in 53.4% patients; folic acid in 16.1%, iron in 6.7%, ferritin in 41.7%,
      calcium in 16.7%, and albumin in 10.3% of the patients. Nineteen women (79.2%)
      had no complication during the pregnancy and two (8.3%) presented with internal
      hernia. The average of newborns weight and length on delivery were 3,037 g and
      48.07 cm, respectively. Children from pregnancies started in the first year of
      post operatory had similar outcomes of children from pregnancies started after 1
      year of surgery. CONCLUSIONS: Pregnancy after bariatric surgery is safe and has
      fewer complications than pregnancy in morbidly obese women. However, the
      recommendation to delay the pregnancy for at least 12-18 months post-operatively
      should be kept.

PMID- 20820940
TI  - Cardiorespiratory fitness and health-related quality of life in bariatric surgery
      patients.
AB  - Health-related quality of life (HRQOL) is impaired in severely obese individuals
      presenting for bariatric surgery. Little is known about the relationship between
      cardiorespiratory fitness (CRF) and HRQOL in these individuals. We hypothesized
      that better HRQOL would be reported by those with higher CRF. In 326 gastric
      bypass patients (mean BMI = 46.5 +/- 7.0; mean age=40.9 +/- 10.1; 83.4% female),
      pre-surgical CRF was quantified as duration (minutes) of a submaximal treadmill
      test to 80% of age-predicted maximal heart rate (MHR). Patients completed both a
      general measure of HRQOL [the Medical Outcome Short Form 36 (SF-36)] and a weight
      specific measure of HRQOL [Impact of Weight on Quality of Life--Lite]. Mean HRQOL
      scores were examined, controlling for age, gender, and BMI. Mean treadmill
      duration was 9.9 +/- 3.1 min, and percent age-predicted MHR was 81.2 +/- 3.0%.
      Higher cardiorespiratory fitness tended to be associated with better physical and
      weight-specific HRQOL. Adjustment for differences in gender, age, and BMI
      attenuated the significance of associations between fitness and physical measures
      from the SF-36, whereas adjustment eliminated significance of associations
      between fitness and weight-specific HRQOL in most cases. Results suggest that CRF
      confers some HRQOL benefits in severely obese adults, though these benefits may
      largely be explained by differences in age, gender, and BMI.

PMID- 20820941
TI  - Evaluation of essential trace and toxic elements in biological samples of normal
      and night blindness children of age groups 3-7 and 8-12 years.
AB  - The most common cause of blindness in developing countries is vitamin A
      deficiency. The World Health Organization estimates 13.8 million children to have
      some degree of visual loss related to vitamin A deficiency. The causes of night
      blindness in children are multifactorial, and particular consideration has been
      given to childhood nutritional deficiency, which is the most common problem found
      in underdeveloped countries. Such deficiency can result in physiological and
      pathological processes that in turn influence biological samples composition.
      Vitamin and mineral deficiency prevents more than two billion people from
      achieving their full intellectual and physical potential. This study was designed
      to compare the levels of Zn, Mg, Ca, K, Na, As, Cd, and Pb in scalp hair, blood,
      and urine of night blindness children age ranged 3-7 and 8-12 years of both
      genders, comparing them to sex- and age-matched controls. A microwave-assisted
      wet acid digestion procedure was developed as a sample pretreatment, for the
      determination of As, Ca, Cd, K, Pb, Mg, Na, and Zn in biological samples of night
      blindness children. The proposed method was validated by using conventional wet
      digestion and certified reference samples of hair, blood, and urine. The
      concentrations of trace and toxic elements were measured by atomic absorption
      spectrophotometer prior to microwave-assisted acid digestion. The results of this
      study showed that the mean values of As, Cd, Na, and Pb were significantly higher
      in scalp hair, blood, and urine samples of male and female night blindness
      children than in referents (p < 0.001), whereas the concentrations of Zn, Ca, K,
      and Mg were lower in the scalp hair and blood but higher in the urine samples of
      night blindness children. These data present guidance to clinicians and other
      professional investigating deficiency of essential mineral elements in biological
      samples (scalp hair and blood) of night blindness children.

PMID- 20820942
TI  - Major and trace elements in zooplankton from the Northern Gulf of California
      during summer.
AB  - We report the distribution of major and trace element concentrations in
      epipelagic zooplankton collected in the Northern Gulf of California in August
      2003. The Bray-Curtis index defined three element assemblages in zooplankton: (1)
      major metals, which included only two elements, Na (3.6-17.0%) and Ca (1.0-4.8%).
      Na had its highest concentrations in the shallow tidally mixed Upper Gulf, where
      high salinity, temperature, and zooplankton biomass (dominated by copepods)
      prevailed. Ca showed its highest concentrations south of Ballenas Channel,
      characterized by tidal mixing and convergence-induced upwelling, indicated by low
      sea-surface temperature, salinity, and zooplankton biomass; (2) Six biological
      essential elements, like Fe (80-9,100 mg kg(-1)) and Zn (20-2,570 mg kg(-1)),
      were detected in high concentrations in zooplankton collected near Guaymas Basin,
      which had high surface temperature and chlorophyll a concentrations. (3) Metals
      of terrigenous origin, such as Sc (0.01-1.4 mg kg(-1)) and Th (0.03-2.3 mg kg(
      1)), and redox-sensitive metals, like Co (3-23.8 mg kg(-1)); this was the
      assemblage with the largest number of elements (15). Both types of elements of
      assemblage 3 had maximum concentrations in the cyclonic eddy that dominates the
      summer circulation in the Northern region. We concluded that sediment
      resuspension by tidal mixing in the Upper Gulf, upwelling south of Ballenas
      Channel, and the cyclonic eddy were key oceanographic features that affected the
      element concentrations of epipelagic zooplankton in the Northern Gulf of
      California. Oceanographic mechanisms such as these may contribute to element
      incorporation in marine organisms in other seas.

PMID- 20820943
TI  - Dynamic changes of CD4+CD25 + regulatory T cells in NOD.H-2h4 mice with iodine
      induced autoimmune thyroiditis.
AB  - Iodine is an essential trace element for thyroid hormone synthesis and
      metabolism, either low or high intake may lead to thyroid disease, but the
      pathogenetic mechanisms by which iodine interacts with the thyroid autoimmune are
      poorly understood. We investigated the dynamic changes of CD4(+)CD25(+)
      regulatory T cells in NOD.H-2(h4) mice with iodine-induced autoimmune thyroiditis
      (AIT), and explore potential immune mechanism of AIT induced by iodine. NOD.H
      2(h4) mice were randomly divided into two groups, and received plain water or
      water containing 0.005% sodium iodide. Eight weeks after iodine provision, the
      incidences of thyroiditis, relative weights of thyroids, and serum thyroglobulin
      antibody titers in the iodine-supplied groups were significantly increased
      compared to the control groups (p < 0.05). The AIT mice had fewer
      CD4(+)CD25(+)Foxp3(+) T cells and reduced Foxp3 mRNA expression in splenocytes
      compared with the controls (p < 0.01), and maintained relatively low levels
      during the development of thyroiditis. The changes described above aggravated
      gradually with the extension of iodine treatment. These data suggest that
      CD4(+)CD25(+) regulatory T cells may be involved in the pathogenesis and
      development of AIT induced by iodine.

PMID- 20820944
TI  - Impairment of spermatogenesis in rats by mercuric chloride: involvement of low
      17beta-estradiol level in induction of acute oxidative stress.
AB  - Mercuric chloride (HgCl(2)) has been shown to affect the male reproductive
      organs, and oxidative stress has been linked with hypospermatogenesis and with
      male infertility. However, the specific mode of impairment of spermatogenesis
      during HgCl(2) exposure has not yet been clarified fully. Because of the
      involvement of 17beta-estradiol (E2) in the male reproductive tract and its
      putative role on spermatogenesis, the present study aimed to investigate the
      possibility that HgCl(2)-induced oxidative stress-mediated modulation of the E2
      level exerts adverse effects on testicular steroidogenic and gametogenic
      activities. HgCl(2) treatment at 50 and 100 ppm for 90 days by continuous oral
      administration in the drink water resulted in significant dose-dependent fashion
      decrease in serum and testicular E(2) levels and an increase in testicular
      testosterone levels in dose-dependent manner, without statistical alteration in
      serum testosterone level among HgCl(2) exposed groups compared to the control.
      Cauda epididymal sperm count and motility were decreased significantly (p <
      0.01), in a dose-dependent manner, in the HgCl(2)-treated groups, and qualitative
      examination revealed inhibition of spermatogenesis and the preferential loss of
      maturing and elongated spermatids. The seminiferous tubules were dilated in
      treated animals. When compared to the control, increase in lipid peroxidation due
      to toxic effects of HgCl2 was accompanied by significant reduction (p < 0.01) in
      antioxidant enzymes activities, superoxide dismutase, catalase, and glutathione
      peroxidase of testes, implicating the presence of oxidative tissue damage.
      Furthermore, these tissue injuries caused functional impairment as evidenced with
      testicular elevated activity of lactate dehydrogenase. Unless oxidative stress
      can lead to cancer development, testis' tumor markers as beta human chorionic
      gonadotropin and alpha-fetoprotein levels have shown no significant differences
      in the HgCl(2)-exposed group compared with respect to the control. Large
      quantities of metal accumulated in the testis tissue are in agreement with the
      testis-activity failure verified in this tissue. These findings suggest that a
      decrease in E2 level after mercury exposure may render testis more susceptible to
      oxidative damage leading to its functional inactivation, thus providing new
      dimension to mechanisms underlying heavy metal-induced male infertility.

PMID- 20820945
TI  - Disseminated carcinoma diagnosed by bone marrow biopsy in patients with
      microangiopathic hemolytic anemia and thrombocytopenia: a report of two cases
      with gastric cancer and a review of the literature.
AB  - INTRODUCTION: Malignancy is often associated with hematological disorders, but
      rarely is the diagnosis of malignancy secondary to the diagnosis of
      microangiopathic hemolytic anemia and thrombocytopenia. CASE REPORTS: We report
      hereby two patients with metastatic gastric carcinoma presenting with
      microangiopathic hemolytic anemia and thrombocytopenia. Despite chemotherapy and
      repeated plasmapheresis in one patient, both patients succumbed shortly after the
      diagnosis of cancer was made. CONCLUSION: A review of the literature regarding
      microangiopathic hemolytic anemia in cancer patients is discussed. In patients
      suffering from microangiopathic hemolytic anemia and thrombocytopenia, malignancy
      should be considered as a possible cause. Early diagnosis of malignancy may be
      critical for determining the patient's prognosis and potentially avoiding
      unnecessary overtreatment.

PMID- 20820946
TI  - Non-viral causes of hepatocellular carcinoma.
AB  - INTRODUCTION: Hepatocellular carcinoma (HCC) is a major cause of cancer
      worldwide. The vast majority of cases occur in individuals with a chronic HBV or
      HCV infection. In addition, a number of metabolic diseases of the liver are
      associated with the development of HCC. PATHOPHYSIOLOGIC MECHANISMS: The
      mechanisms responsible for the progression of the metabolic liver disease and HCC
      differ from those associated with viral liver disease. CONCLUSIONS: The purpose
      of this report is to describe the mechanisms responsible for the disease
      progression and HCC in case of metabolic liver disease. A secondary goal is to
      identify the frequency of HCC development in the disorders described.

PMID- 20820947
TI  - The use of the condensed single protein production system for isotope-labeled
      outer membrane proteins, OmpA and OmpX in E. coli.
AB  - Gram-negative bacteria consist of two independent membranes, the inner
      cytoplasmic membrane and the outer membrane. The outer membrane contains a number
      of beta-barrel proteins such as OmpF, OmpC, OmpA, and OmpX. In this article, we
      explored to use the condensed Single Protein Production (cSPP) system for isotope
      labelling of OmpA and OmpX for NMR structural study, both of which are known to
      consist of eight beta-strands forming a barrel in the outer membrane. Using a
      deletion strain lacking all major outer membrane proteins, both OmpA and OmpX
      were expressed well in a 20-fold cSPP system. We demonstrated that outer membrane
      fractions prepared from the cSPP system in M9 medium containing 15N-NH4Cl can be
      directly used for NMR structural study of the outer mebrane proteins without any
      further purification to get excellent [1H-15N]-TROSY spectra. This method would
      be quite valuable for the study of pure proteins in their native membrane
      environment without the need of purification and reconstitution.

PMID- 20820948
TI  - Subdividing the M1 stage of liver metastasis for nasopharyngeal carcinoma to
      better predict metastatic survival.
AB  - In nasopharyngeal carcinoma (NPC), the M1 stage of the TNM classification does
      not differentiate between the site of metastasis or the number of metastatic
      lesions. However, NPC patients with lung or bone metastases survive longer than
      do those with liver metastasis (LM). We subdivided the M1 stage of LM to better
      predict survival in these patients. From the records of 305 NPC patients with LM
      treated at Sun Yat-sen University Cancer Center between January 2000 and December
      2007, we determined the effects of clinical characteristics and the
      subclassifications of the M1 stage for LM characteristics [the number, size,
      timing (synchronous vs. metachronous), and distribution of metastases and
      metastases to other organs] on survival since the diagnosis of LM. Metastatic
      survival rates were 62% at 1 year, 31% at 2 years, and 21% at 3 years. Having 1-3
      metastatic lesions, having lesions less than 5 cm in diameter, and having
      unilobular LM were better univariate predictors of metastatic survival. Better
      survival was independently predicted by having one to three (vs. more than three)
      metastatic lesions (hazards ratio=0.52; 95% CI=0.33-0.82) and unilobular (vs.
      bilobular) lesions (hazards ratio=0.35; 95% CI=0.22-0.57). The current report
      constitutes large samples of LM from NPC from our single institution with
      correlation between LM characteristics and metastatic survival. Patients with NPC
      and one to three liver metastases or unilobular metastases survive longer than
      their counterparts, and aggressive treatment should be considered.

PMID- 20820949
TI  - Medico-legal autopsy in postoperative hemodynamic collapse following coronary
      artery bypass surgery.
AB  - Sudden unexpected postoperative hemodynamic collapse with a high mortality
      develops in 1-3% of patients undergoing coronary artery bypass surgery (CABG).
      The contribution of surgical graft complications to this serious condition is
      poorly known and their demonstration at autopsy is a challenging task. Isolated
      CABG was performed in 8,807 patients during 1988-1999. Of the patients, 76 (0.9%)
      developed sudden postoperative hemodynamic collapse resulting in subsequent
      emergency reopening of the median sternotomy and open cardiac massage. Further
      emergency reoperation could be performed in 62 (82%) whereas 14 patients died
      prior to reoperation and a further 21 did not survive the reoperation or died a
      few days later. All 35 (46%) patients who did not survive were subjected to
      medico-legal autopsy combined with postmortem cast angiography. By combining
      clinical data with autopsy and angiography data, various types of graft
      complications were observed in 27 (36%, 1.3 per patient) of the 76 patients with
      hemodynamic collapse. There were no significant differences in the frequency (33
      vs. 40%) or number of complicated grafts per patient (1.2 vs. 1.4) between those
      who survived reoperation and who did not. Autopsy detected 25 major and minor
      findings not diagnosed clinically. Postmortem cast angiography visualized 2 graft
      twists not possible to detect by autopsy dissection only. Surgical graft
      complications were the most frequent single cause for sudden postoperative
      hemodynamic collapse in CABG patients leading to a fatal outcome in almost half
      of the cases. Postmortem angiography improved the accuracy of autopsy diagnostics
      of graft complications.

PMID- 20820950
TI  - Management of acute lung injury/ARDS.
AB  - Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are
      disorders of pulmonary inflammation characterized by hypoxemia and respiratory
      failure. Children have varying incidence of ALI/ARDS from 2.2 to 16 per 100,000
      pediatric population associated with high morbidity, mortality, and financial
      burden. The diagnostic criteria include: acute onset, severe arterial hypoxemia
      resistant to oxygen therapy alone (PaO2/FIO2 ratio <= 200 for ARDS and <= 300 for
      ALI), diffuse pulmonary inflammation (bilateral infiltrates on chest radiograph)
      and No evidence of left atrial hypertension. Management includes ventilatory
      therapy including lower tidal volume, relatively high PEEP and supportive care.
      Guidelines for diagnosis, ventilator management, rescue therapies and supportive
      care are being discussed in the protocol.

PMID- 20820951
TI  - Thalassemia, protein C, protein S and infarct: correlation?

PMID- 20820952
TI  - Should niacin be the preferred drug to add to a statin?

PMID- 20820953
TI  - Omega-3 fatty acids, mercury, and selenium in fish and the risk of cardiovascular
      diseases.
AB  - Fish consumption is associated with lower risk of cardiovascular disease. Some
      fish species also contain methylmercury, which may increase cardiovascular risk,
      as well as selenium, a trace element that could counter the effects of
      methylmercury or have beneficial effects itself. These potentially conflicting
      effects have created public confusion about the risks and benefits of fish
      consumption in adults. We examined the evidence for cardiovascular effects of
      fish consumption, particularly effects of marine omega-3 fatty acids,
      methylmercury, and selenium. Compelling evidence indicates that modest fish
      consumption substantially reduces cardiovascular risk, in particular cardiac
      mortality, related at least partly to benefits of omega-3 fatty acids. In
      contrast, observational studies and (for selenium) clinical trials demonstrate
      mixed and inconclusive results for cardiovascular effects of methylmercury and
      selenium. Net health benefits of overall fish consumption in adults are clear.
      Quantitative risk-benefit analyses of cardiovascular effects of consuming
      specific fish species, based on joint contents of fatty acids, methylmercury, and
      selenium, cannot currently be performed until the cardiovascular effects of
      methylmercury and selenium are established.

PMID- 20820954
TI  - Effects of whole grains on coronary heart disease risk.
AB  - Characterizing which types of carbohydrates, including whole grains, reduce the
      risk for coronary heart disease (CHD) is challenging. Whole grains are
      characterized as being high in resistant carbohydrates as compared with refined
      grains, meaning they typically are high in fiber, nutrients, and bound
      antioxidants. Whole grain intake consistently has been associated with improved
      cardiovascular disease outcomes, but also with healthy lifestyles, in large
      observational studies. Intervention studies that assess the effects of whole
      grains on biomarkers for CHD have mixed results. Due to the varying nutrient
      compositions of different whole grains, each could potentially affect CHD risk
      via different mechanisms. Whole grains high in viscous fiber (oats, barley)
      decrease serum low-density lipoprotein cholesterol and blood pressure and improve
      glucose and insulin responses. Grains high in insoluble fiber (wheat) moderately
      lower glucose and blood pressure but also have a prebiotic effect. Obesity is
      inversely related to whole grain intake, but intervention studies with whole
      grains have not produced weight loss. Visceral fat, however, may be affected
      favorably. Grain processing improves palatability and can have varying effects on
      nutrition (e.g., the process of milling and grinding flour increases glucose
      availability and decreases phytochemical content whereas thermal processing
      increases available antioxidants). Understanding how individual grains, in both
      natural and processed states, affect CHD risk can inform nutrition
      recommendations and policies and ultimately benefit public health.

PMID- 20820956
TI  - Preconception counseling for adolescent females with type 1 diabetes: the READY
      Girls Program.

PMID- 20820955
TI  - Nuts and berries for heart health.
AB  - Nuts are nutrient-dense foods with complex matrices rich in unsaturated fatty
      acids and other bioactive compounds, such as L-arginine, fiber, minerals,
      tocopherols, phytosterols, and polyphenols. By virtue of their unique
      composition, nuts are likely to beneficially impact heart health. Epidemiologic
      studies have associated nut consumption with a reduced incidence of coronary
      heart disease in both genders and diabetes in women. Limited evidence also
      suggests beneficial effects on hypertension and inflammation. Interventional
      studies consistently show that nut intake has a cholesterol-lowering effect and
      there is emerging evidence of beneficial effects on oxidative stress,
      inflammation, and vascular reactivity. Blood pressure, visceral adiposity, and
      glycemic control also appear to be positively influenced by frequent nut
      consumption without evidence of undue weight gain. Berries are another plant food
      rich in bioactive phytochemicals, particularly flavonoids, for which there is
      increasing evidence of benefits on cardiometabolic risk that are linked to their
      potent antioxidant power.

PMID- 20820957
TI  - The genetics of insulin resistance: Where's Waldo?
AB  - The physiologic hallmarks of type 2 diabetes are insulin resistance in hepatic
      and peripheral tissues and pancreatic beta-cell dysfunction. Thus, genetic loci
      underlying susceptibility to type 2 diabetes are likely to map to one of these
      endophenotypes. Genome-wide association studies have now identified up to 38
      susceptibility loci for type 2 diabetes and a number of other loci underlying
      variation in type 2 diabetes-related quantitative traits. The majority are of
      unknown biology or map to pancreatic beta-cell dysfunction. A seemingly
      disproportionate minority map to insulin resistance. We briefly discuss the known
      insulin resistance loci identified from genome-wide association, and then discuss
      reasons why additional insulin resistance loci have not been identified. We
      present alternative views that may partly explain the apparent dearth of insulin
      resistance loci contributing to genetic susceptibility to type 2 diabetes, rather
      than focus on traditional issues such as study design and sampling, which have
      been addressed elsewhere.

PMID- 20820958
TI  - Childhood rhabdomyosarcoma: new insight on biology and treatment.
AB  - Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. The
      two most common histologic variants are the embryonal and alveolar subtypes.
      Although successive collaborative group clinical trials have improved survival
      rates for many RMS patients, the outcome for those patients with metastatic or
      recurrent disease remains poor. Recent studies have pointed to a possible
      mesenchymal stem cell as the progenitor for alveolar RMS. Other studies have
      implicated several cellular mechanisms and pathways being involved in RMS
      pathogenesis and survival, such as the cyclin-dependent kinase inhibitors,
      insulin-like growth factor pathway, and the mammalian target of rapamycin
      pathway, thus providing potential avenues for targeted therapy. Recent clinical
      trials have tried to improve risk stratification and prediction of clinical
      outcome based upon clinical or radiographic response to initial therapy and also
      to determine the role of high-dose chemotherapy with stem cell rescue in high
      risk RMS patients.

PMID- 20820959
TI  - Can anthracycline therapy for pediatric malignancies be less cardiotoxic?
AB  - Anthracyclines have a central role in the treatment of cancer in pediatric
      patients but confer an increased risk of cardiac dysfunction. Several strategies
      have been employed to help reduce anthracycline-induced cardiotoxicity, including
      pretreating the patient with the iron chelator dexrazoxane and infusing the dose
      of anthracycline over a longer period. Much focus has also been placed on the
      development of methods that decrease the toxicity of parent compounds,
      specifically through the use of drug carriers such as liposomes, and on the
      development of new, potentially less toxic anthracycline derivatives, such as
      amrubicin and pixantrone. We provide a review of these strategies, focusing on
      studies in pediatric patients when available, and support the idea that
      anthracycline therapy can be less cardiotoxic in pediatric patients.

PMID- 20820960
TI  - Maintenance and consolidation strategies in non-Hodgkin's lymphoma: A review of
      the data.
AB  - Results of treatment for patients with non-Hodgkin's lymphomas have significantly
      improved over the last decade, especially following the discovery that anti-CD20
      antibody therapy can significantly change the outlook for patients with both
      aggressive and indolent lymphomas. Although investigators have previously
      attempted to prevent relapses by intensifying chemotherapy programs for patients
      with poor-risk disease, further improvements in treatment will require
      development of biologic agents that can be added to current programs and
      exploitation of currently available drugs that can prevent recurrence of these
      diseases with good tolerability. This review analyzes currently available plans
      that can be used to maintain responses or "consolidate" initial responses to
      therapy, programs that may prevent relapse and potentially cure more patients
      with lymphomas, with a review of current ongoing trials designed along these
      lines.

PMID- 20820961
TI  - Fetal epigenetic mechanisms and innate immunity in asthma.
AB  - Allergy and asthma are chronic inflammatory diseases that result from complex
      gene-environment interactions. Recent evidence points to the importance of
      prenatal and postnatal developmental processes in the maturation of balanced
      immune responses. Novel data indicate that epigenetic mechanisms contribute to
      the development of T-helper-cell function. Environmental factors, including
      diesel exhaust particles, vitamins, and tobacco smoke, operate through such
      mechanisms. Furthermore, the role of environmental microbes provides another-and
      maybe an even more important-group of exogenous exposures that operate in this
      critical time frame. A better understanding of fetal immuno-maturation conditions
      will provide the basis for the development of novel allergo-protective clinical
      strategies.

PMID- 20820962
TI  - The pathophysiology of the aging skeleton.
AB  - In recent decades the population of both elderly men and women has grown
      substantially worldwide. Aging is associated with a number of pathologies
      involving various organs including the skeleton. Age-related bone loss and
      resultant osteoporosis put the elderly population at an increased risk for
      fractures and morbidity. Fortunately, in parallel our understanding of this
      malady has also grown substantially in recent years. A number of clinical as well
      as translational studies have been pivotal in providing us with an understanding
      of the pathophysiology of this condition. This article discusses the current
      concepts of age-related modulation of the skeleton involving intrinsic factors
      such as genetics, hormonal changes, levels of oxidative stress, and changes in
      telomere length, as well as extrinsic factors such as nutritional and lifestyle
      choices. It also briefly outlines recent studies on the relationship between bone
      and fat in the marrow as well as the periphery.

PMID- 20820964
TI  - Investigation of optimal viewing size for detecting nodular ground-glass opacity
      on high-resolution computed tomography with cine-mode display.
AB  - We evaluated the effect of the displayed image sizes on observers' ability to
      detect nodular ground-glass opacity (n-GGO) on CT and investigated the optimal
      viewing size for soft-copy reading at CT screening for lung cancer. A total of 46
      patients' high-resolution computed tomography (HRCT) images (22 patients with one
      GGO; 24 without GGO) were displayed on a monochromatic liquid crystal display
      monitor at a resolution of 1,200 * 1,600. HRCT was presented on the screen with
      cine-mode display. We compared two viewing sizes (original size, i.e., the image
      displayed with a zoom factor of 1 in which each pixel value in the image is
      displayed as one pixel on the display: 13 cm * 13 cm; fit size, i.e., by zooming
      the captured image until it occupies the entire screen: 30 cm * 30 cm) in terms
      of radiologists' performance for detecting n-GGO on HRCT and the viewing times
      required for soft-copy reading decisions. Observer performance was analyzed in
      terms of the receiver operating characteristic (ROC) curve. A statistically
      significant improvement was found with the original size in the average area
      under-the-ROC curve values for the accuracy of diagnosis and the viewing times
      compared to the fit size (P < 0.05). The original size with cine-mode display
      leads to increased lung GGO detection at CT screening for lung cancer, and the
      reduced time spent performing the diagnosis offers cost savings.

PMID- 20820963
TI  - Evolving concepts in neurogenic osteoporosis.
AB  - Convincing evidence has accumulated of regulation of bone by the central nervous
      system. The neural connection between brain and bone is mediated centrally by
      classic neurotransmitters and several neuropeptides, and peripherally by many of
      the same neurotransmitters and neuropeptides, albeit with actions opposite to
      their central effects. Pharmacologic blockade of beta2-adrenergic receptors or
      disruption of the gene encoding them increases bone mass, whereas increased
      activity of the sympathetic nervous system (SNS) contributes to bone loss.
      Brainstem serotonergic neurons regulate SNS activity and its modulation by
      leptin. Physiologic stimulation of osteoblastic nicotinic receptors results in
      proliferation and deposition of bone, whereas higher levels inhibit osteoblast
      function. Activation of sensory nerves has a centrally mediated action on bone,
      albeit poorly understood. The relative importance of, and interactions between
      autonomic, sensory, and peripheral nervous system actions on bone mass are also
      not clear in healthy individuals, and less so in pathologic states.

PMID- 20820965
TI  - Measurement of manganese content in various organs in rats with or without
      glucose stimulation.
AB  - Our purpose in this study was to assess the manganese (Mn) content in various
      organs in rats with or without glucose stimulation in vivo and in vitro by using
      magnetic resonance imaging (MRI) and polarized Zeeman atomic absorption
      spectrophotometry (PZAAS), respectively. MRI studies were performed in 12 rats
      using a 1.5-T MRI system. The rats were injected intravenously with saline (6
      ml/kg) (saline-stimulated group, n = 6) or glucose (2.34 g/kg) (glucose
      stimulated group, n = 6). Ten minutes after saline or glucose administration,
      MnCl2 (0.02 mmol/kg) was injected intravenously, followed by 6 MRI studies at 8
      min intervals. After the last MRI study, rats were killed, and the Mn
      concentrations in various organs were measured using PZAAS. There was a
      discrepancy between in vivo and in vitro measurements, which appeared to be due
      to the partial volume effect and/or the contribution of extracellular Mn. The Mn
      concentration in the pancreas, normalized to that in the liver in the glucose
      stimulated group, increased significantly compared to that in the saline
      stimulated group, suggesting that the influx of Mn into beta cells in the
      pancreas increased in response to glucose stimulation. This study suggested that
      the measurement of the change in the Mn concentration due to glucose stimulation
      using PZAAS was effective for evaluating beta-cell function in the pancreas.

PMID- 20820966
TI  - Calculation of air-kerma rate of diagnostic X-ray generators.
AB  - As one type of basic physical data related to the calculation of the construction
      of X-ray examination room shielding, we investigated the air-kerma rate 1 m from
      the source of the useful beam focus per unit current time product. Compared to
      the X-ray energy penetration values obtained in prior research, we obtained
      higher values. We found three causes for this discrepancy: (1) the X-ray tube
      total filtration (increasing total filtration reduces air kerma), (2) the tube
      voltage ripple percentage (increased voltage ripple reduces air kerma, and (3)
      the target angle (increasing the target angle increases the air kerma). On
      standardizing (1)-(3), we confirmed that our values mostly matched those obtained
      in past research. Consequently, when one employs the air-kerma rate that results
      from the consideration of (1)-(3), without pursuing a path of excessive safety,
      calculation of shielding under clinical conditions is possible.

PMID- 20820967
TI  - Overlap of radiation field and radiation field shape in cardiac catheterization.
AB  - The radiation field shape for cardiac catheterization has changed from being
      circular to being rectangular with the spread of flat-panel detector systems. A
      rectangular radiation field provides a wide fluoroscopy field to the four corners
      of a subject area; however, in cardiac catheterization, there is not much usable
      information around the four corners at several angles, and this tends to be
      regarded as a meaningless radiation exposure. Hence, overlap of radiation fields
      has been of concern recently. The authors changed field sizes/fluoroscopy angles
      and examined entrance dose rates to study radiation field shapes and
      configurations of radiation exposure to patients, and they discussed a radiation
      exposure reduction method. In measurements of phantom entrance dose rates, we
      considered right anterior oblique (RAO) directions, cranial (CRA) directions and
      RAO-CRA directions and found that entrance dose rates rose considerably,
      particularly at the RAO-CRA. In the study of radiation field overlap, we discuss
      radiation field shapes (rectangular/circular) as well as angles. In the RAO-CRA
      directions, differences occurred in angles of non-overlapping radiation field by
      differences in radiation field shapes. For RAO-CRA, compared with the RAO and CRA
      directions, entrance dose rates increased with an increase in angle. When
      convenience in clinics is considered, the utilization frequency of the four
      corners of a rectangular field is low. When one considers the increases in
      radiation exposure caused by radiation field overlap, it is more effective to use
      circular radiation fields.

PMID- 20820968
TI  - Treatment of central nervous system lymphoma in rats with intraventricular
      rituximab and serum.
AB  - B cell lymphomas often develop in the central nervous system (CNS). Although
      rituximab (RTX) has been widely used for most B cell lymphomas, the efficacy for
      CNS lymphomas has yet to be elucidated. A major concern is that RTX might not
      reach lymphoma lesions, and either the antibody-dependent cellular cytotoxicity
      or complement-dependent cytotoxicity might not substantially operate in the CNS
      environment. Here we investigated the potential usefulness of co-administering
      RTX and human serum intraventricularly in nude rats carrying human B cell
      lymphomas in the CNS. Raji, a CD20-positive lymphoma cell line, was inoculated
      into the cerebrum of F344 (rnu/rnu) nude rats. After several days, RTX and human
      serum were delivered into the ipsilateral lateral ventricle via a cannula.
      Intraventricularly administered RTX was localized specifically at the lymphoma
      lesions, indicating that RTX penetrated the ependymal layer of the lateral
      ventricle to reach the tumor lesion, where it specifically bound to the lymphoma
      cells. The combination of RTX and serum (n = 12), but not RTX alone (n = 13),
      significantly extended the survival of the rats (P = 0.049). Intraventricular
      administration of RTX and serum in a rat/human CNS lymphoma model might be a
      potential novel treatment for CNS lymphomas of B cell origin. Clinical trials are
      warranted.

PMID- 20820969
TI  - Congenital dyserythropoietic anemia.
AB  - Congenital dyserythropoietic anemias (CDAs) are a heterogeneous group of rare
      hereditary disorders of erythropoiesis characterized by morphologic abnormal
      erythroblasts in the bone marrow. Three types of the disease are known as type I,
      II and III, and the variant type of CDA and several minor subgroups of CDA have
      been also reported since the first classification. Recently, responsible genes
      for type I (CDAN1) and type II (SEC23B) have been identified and the molecular
      pathogenesis of the disease is currently being explored. Although CDAs rarely
      transform to myelodysplastic syndrome or leukemia, the disease is important to
      understand the mechanism of hemopoiesis in humans.

PMID- 20820970
TI  - Hemophagocytic lymphohistiocytosis associated with myelodysplastic syndromes.

PMID- 20820971
TI  - Implementation science of pre-exposure prophylaxis: preparing for public use.
AB  - As efficacy trials of antiretroviral pre-exposure prophylaxis (PrEP) continue, a
      growing literature has begun anticipating the potential challenges of
      implementing PrEP for HIV prevention. These efforts coincide with a shift toward
      combination interventions for preventing HIV, which integrate biomedical,
      behavioral, and structural components. The optimal implementation of PrEP would
      exemplify this combination model, incorporating not only PrEP drugs, but also HIV
      testing, safety screening, behavioral interventions addressing adherence and risk
      behavior, and long-term monitoring. Efforts to plan for PrEP implementation
      therefore present an opportunity to advance the science of implementation and
      delivery in HIV prevention, in order to better address the challenges of scaling
      up combination approaches. We review the published and unpublished literature on
      PrEP implementation, organizing themes into five categories: scientific
      groundwork, regulatory and policy groundwork, stakeholder and infrastructure
      groundwork, delivery, and long-term monitoring. The lessons from PrEP planning
      can benefit the scale-up of future combination interventions.

PMID- 20820972
TI  - Retention in care among HIV-infected patients in resource-limited settings:
      emerging insights and new directions.
AB  - In resource-limited settings--where a massive scale-up of HIV services has
      occurred in the last 5 years--both understanding the extent of and improving
      retention in care presents special challenges. First, retention in care within
      the decentralizing network of services is likely higher than existing estimates
      that account only for retention in clinic, and therefore antiretroviral therapy
      services may be more effective than currently believed. Second, both magnitude
      and determinants of patient retention vary substantially and therefore
      encouraging the conduct of locally relevant epidemiology is needed to inform
      programmatic decisions. Third, socio-structural factors such as program
      characteristics, transportation, poverty, work/child care responsibilities, and
      social relations are the major determinants of retention in care, and therefore
      interventions to improve retention in care should focus on implementation
      strategies. Research to assess and improve retention in care for HIV-infected
      patients can be strengthened by incorporating novel methods such as sampling
      based approaches and a causal analytic framework.

PMID- 20820973
TI  - Current immunochemotherapy strategies in follicular lymphoma.
AB  - Nowadays, there is no consensus about the best treatment for patients with
      follicular lymphoma (FL) in differing situations. In frontline treatment, a
      watchful waiting policy remains a good option if the patient has no risk
      criteria; the role of rituximab is under investigation in this setting. In
      patients needing therapy, immunotherapy or immunochemotherapy are the best
      options; although it has not been established which chemotherapy, including
      cyclophosphamide, vincristine, and prednisone (CVP); cyclophosphamide,
      adriamycin, vincristine, and prednisone (CHOP); fludarabine, or bendamustine
      combinations, is the best partner for rituximab. Following frontline treatment,
      recent and still unpublished data strongly suggest a role for maintenance with
      rituximab, instead of observation only. At relapse, immunochemotherapy is the
      standard induction approach. The role of maintenance after induction is well
      established, although comparative studies with autologous stem-cell
      transplantation (ASCT) or other combinations are warranted. The role of ASCT in
      this setting is a matter of discussion. Other monoclonal antibodies, as well as
      vaccines and other immunotherapies, are currently under investigation. Finally,
      allogeneic transplantation should be reserved for a very select group of young
      high-risk patients in the setting of clinical trials.

PMID- 20820974
TI  - Molecular changes occurring during reverse remodelling following left ventricular
      assist device support.
AB  - Remodelling is the central feature that occurs in the progression of heart
      failure. However, unloading of the heart with a left ventricular assist device
      (LVAD) can lead to reversal of many of the remodelling changes even in patients
      with advanced heart failure. LVAD unloading can also lead to improved myocardial
      function and this improvement can be sufficient to allow removal of the device
      leaving the patient to lead a normal life. We review the molecular changes that
      have been demonstrated with LVAD unloading in patients bridged to transplantation
      and also those that have occurred in the myocardium of patients that have
      recovered their myocardial function enough to have the device removed. Changes in
      both the myocyte and the matrix are reviewed.

PMID- 20820975
TI  - Current use of the EXCOR pediatric ventricular assist device.
AB  - Since its initial application in the pediatric patient population, the Berlin
      Heart EXCOR ventricular assist device has become a widely accepted form of
      mechanical circulatory support in Europe and the USA. The versatility of the
      device makes it ideal for pediatric patients because it can be tailored to the
      size and needs of the patient. In this review, we will explore the broad range of
      clinical applications of this device including bridge to cardiac transplantation,
      bridge to recovery, and bridge to bridge implantation where the need for cardiac
      transplantation may be unclear but long-term mechanical support may be required.

PMID- 20820978
TI  - Erythropoietin ameliorates the reduced migration of human fibroblasts during in
      vitro hypoxia.
AB  - Erythropoietin promotes the formation of granulation tissue when administered to
      soft tissue wounds and it was shown to be most effective under tissue hypoxia.
      However, the action of erythropoietin on the cellular level is not well
      understood. In order to get a better insight into these processes, an in vitro
      wound healing assay was applied. Two main players of soft tissue healing
      fibroblasts and microvascular endothelial cells-were used as mono- and co
      cultures, subsequently inflicting in vitro wounds. Cell migration, proliferation,
      the differentiation of fibroblasts to myofibroblasts, and the release of vascular
      endothelial cell growth factor A and angiogenin were quantified in response to
      hypoxia and erythropoietin (5 IU/ml). Erythropoietin supplementation did neither
      affect proliferation nor migration of endothelial cells and fibroblasts under
      normoxia. Under hypoxia, the reduced fibroblast migration was ameliorated by
      erythropoietin. This effect coincided with an attenuated release of vascular
      endothelial growth factor A, whereas angiogenin release was unaffected by
      erythropoietin. The in vitro model applied in this study may represent an
      adequate approximation to certain aspects of the in vivo status of soft tissue
      regeneration and the results might serve to interpret the in vivo efficiency of
      erythropoietin at the cellular level: Erythropoietin has different impacts on the
      cells in normoxia and hypoxia. Its positive influence on fibroblast migration
      during hypoxia seems to support the strategies of applying erythropoietin in
      those chronic wounds, which exhibit fibroblastic dysfunction although good
      vascularisation is present.

PMID- 20820976
TI  - Cadherins in cerebellar development: translation of embryonic patterning into
      mature functional compartmentalization.
AB  - Cadherins are cell adhesion molecules with multiple morphogenic functions in
      brain development, for example, in neuroblast migration and aggregation, axon
      navigation, neural circuit formation, and synaptogenesis. More than 100 members
      of the cadherin superfamily are expressed in the developing and mature brain.
      Most of the cadherins investigated, in particular classic cadherins and delta
      protocadherins, are expressed in the cerebellum. For several cadherin subtypes,
      expression begins at early embryonic stages and persists until mature stages of
      cerebellar development. At intermediate stages, distinct Purkinje cell clusters
      exhibit unique rostrocaudal and mediolateral expression profiles for each
      cadherin. In the chicken, mouse, and other species, the Purkinje cell clusters
      are separated by intervening raphes of migrating granule cells. This pattern of
      Purkinje cell clusters/raphes is, at least in part, continuous with the
      parasagittal striping pattern that is apparent in the mature cerebellar cortex,
      for example, for zebrin II/aldolase C. Moreover, subregions of the deep
      cerebellar nuclei, vestibular nuclei and the olivary complex also express
      cadherins differentially. Neuroanatomical evidence suggests that the nuclear
      subregions and cortical domains that express the same cadherin subtype are
      connected to each other, to form neural subcircuits of the cerebellar system.
      Cadherins thus provide a molecular code that specifies not only embryonic
      structures but also functional cerebellar compartmentalization. By following the
      implementation of this code, it can be revealed how mature functional
      architecture emerges from embryonic patterning during cerebellar development.
      Dysfunction of some cadherins is associated with psychiatric diseases and
      developmental impairments and may also affect cerebellar function.

PMID- 20820979
TI  - RNA interference-directed caveolin-1 knockdown sensitizes SN12CPM6 cells to
      doxorubicin-induced apoptosis and reduces lung metastasis.
AB  - Human renal cell carcinoma (HRCC) is characterized by a high level of resistance
      to all treatment modalities. Therefore, the investigation of global gene
      expression in HRCC might help understand its biologic behavior and develop
      treatment strategies. Using cDNA microarray analysis, we initially compared gene
      expression profiles between HRCCs and adjacent normal tissues, and found that 87
      were up-regulated and 127 genes were down-regulated. Next, a subset of genes,
      twofold differentially expressed, were validated by Northern blotting.
      Unexpectedly, caveolin-1, a gene reported to be a tumor suppressor gene, was
      found to be up-regulated in HRCC tissues. Expression level of caveolin-1 in
      SN12CPM6 (high metastatic clone) was higher than in SN12C (low metastatic clone),
      and SN12CPM6 was more resistant to doxorubicin (DXR) than SN12C. Caveolin-1 gene
      was slightly induced in surviving SN12C cells after DXR treatment. Furthermore,
      SN12CPM6-siCav1 cells, which were transfected with siRNA of cavelon-1 gene, were
      more sensitive to DXR, compared to SN12CPM6, but reduction of caveolin-1 gene
      expression did not affect tumor formation in subcapsule of kidney and lung
      metastasis. On the other hand, induction of caveolin-1 gene affected the
      production of lung metastasis under anti-cancer drug treatment: the incidence of
      pulmonary metastasis was significantly lower in SCID mice injected with SN12CPM6
      siCav1 cells, and the number of pulmonary nodules decreased significantly (p =
      0.0004). The above results together suggest that caveolin-1 may confer a growth
      advantage to cancer cells during DXR chemotherapy and surviving HRCC cells
      eventually might develop lung metastasis.

PMID- 20820980
TI  - Influence of the interaction between nodal fibroblast and breast cancer cells on
      gene expression.
AB  - Our aim was to evaluate the interaction between breast cancer cells and nodal
      fibroblasts, by means of their gene expression profile. Fibroblast primary
      cultures were established from negative and positive lymph nodes from breast
      cancer patients and a similar gene expression pattern was identified, following
      cell culture. Fibroblasts and breast cancer cells (MDA-MB231, MDA-MB435, and
      MCF7) were cultured alone or co-cultured separated by a porous membrane (which
      allows passage of soluble factors) for comparison. Each breast cancer lineage
      exerted a particular effect on fibroblasts viability and transcriptional profile.
      However, fibroblasts from positive and negative nodes had a parallel
      transcriptional behavior when co-cultured with a specific breast cancer cell
      line. The effects of nodal fibroblasts on breast cancer cells were also
      investigated. MDA MB-231 cells viability and migration were enhanced by the
      presence of fibroblasts and accordingly, MDA-MB435 and MCF7 cells viability
      followed a similar pattern. MDA-MB231 gene expression profile, as evaluated by
      cDNA microarray, was influenced by the fibroblasts presence, and HNMT, COMT,
      FN3K, and SOD2 were confirmed downregulated in MDA-MB231 co-cultured cells with
      fibroblasts from both negative and positive nodes, in a new series of RT-PCR
      assays. In summary, transcriptional changes induced in breast cancer cells by
      fibroblasts from positive as well as negative nodes are very much alike in a
      specific lineage. However, fibroblasts effects are distinct in each one of the
      breast cancer lineages, suggesting that the inter-relationships between stromal
      and malignant cells are dependent on the intrinsic subtype of the tumor.

PMID- 20820981
TI  - Circulating LTD4 in patients with hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a type of inflammation-related cancer that
      usually follows chronic inflammations. Leukotriene D4 (LTD4) is a potent
      biologically active arachidonic acid-derived lipid mediator that is intimately
      involved in inflammations and cancers. Although previous researches found
      overexpression of LTD4 in several other cancers, the circulating LTD4 level in
      HCC remains unknown. The aim of this study was to examine concentrations of LTD4
      and analyze its roles in HCC. The results showed that remarkably high circulating
      LTD4 in HCC versus healthy subjects (p < 0.001). The levels of LTD4 were neither
      associated with parameters expressing tumor burden, such as AFP, nor with
      inflammation factors AST and gamma-GT. In addition, the significant increase of
      circulating LTD4 levels was obtained in patients with HCC accompanied by chronic
      hepatitis B (CHB), compared with those patients suffering HCC alone(P < 0.05).
      Furthermore, although the slightly lower levels of LTD4 were detected in HCC
      patients with non-metastasis and therapy compared with metastasis and non
      therapy, no significant differences were detected. Taken together, the levels of
      circulating LTD4 are elevated in HCC and it may participate in the pathogenesis
      of HCC as an inflammatory factor from CHB disease to HCC.

PMID- 20820983
TI  - Multicenter phase II study of weekly paclitaxel plus S-1 combination chemotherapy
      in patients with advanced gastric cancer.
AB  - BACKGROUND: A multicenter phase II study was conducted to evaluate the efficacy
      and safety of a combination regimen of weekly paclitaxel plus S-1 in patients
      with advanced gastric cancer. METHODS: Patients with previously untreated
      metastatic or recurrent gastric cancer received intravenous paclitaxel 50 mg/m(2)
      on days 1, 8, and 15, plus oral S-1 40 mg/m(2) b.i.d. on days 1 to 14 followed by
      2 weeks off, in a 28-day cycle. RESULTS: A total of 54 patients were registered.
      All of them had measurable disease and were determined to be eligible for the
      present study. Two complete responses and 23 partial responses were confirmed,
      giving an overall response rate of 46.3%. At a final follow up of 3 years, the
      median progression-free survival and median overall survival were 6.0 and 14.3
      months, respectively. Grade 3 neutropenia occurred in 14 patients, and grade 4 in
      1 patient (total, 27.8%). The most serious nonhematological toxicity was
      diarrhea, where grade 3 occurred in 5 patients (9.3%). There were no treatment
      related deaths. CONCLUSION: A combination of weekly paclitaxel plus S-1 was found
      to be well tolerated and effective in patients with advanced gastric cancer.
      Further investigation with comparative trials is needed for confirmation.

PMID- 20820982
TI  - Lymph node dissection in the resection of gastric cancer: review of existing
      evidence.
AB  - Gastric cancer is one of the leading causes of cancer-related death worldwide.
      Surgery is the only curative therapy for localized gastric cancer, but the extent
      of regional lymphadenectomy has been a matter of considerable debate. Extended
      resections that are regarded as standard procedures in some Asian countries,
      including Japan and Korea, have not been shown to be as effective in Western
      countries. The extent of lymphadenectomy for advanced gastric cancer has been
      studied in many prospective randomized controlled trials. On the other hand,
      patients with early gastric cancer have an excellent survival rate (>90%) after
      radical surgery. Lymph node metastasis from early gastric cancer is relatively
      infrequent. Therefore, it might be practical to perform less invasive surgery for
      early gastric cancer. In this review article, we examine the evidence for lymph
      node dissection as radical surgery in advanced gastric cancer and the possibility
      of limited resection for early gastric cancer.

PMID- 20820984
TI  - Randomized phase II study of sequential docetaxel and irinotecan with 5
      fluorouracil/folinic acid (leucovorin) in patients with advanced gastric cancer:
      the GATAC trial.
AB  - BACKGROUND: The optimal chemotherapy in patients with advanced gastric carcinoma
      (GC) is yet to be determined. We compared sequential administration of docetaxel
      and irinotecan, both in combination with infused 5-fluorouracil/leucovorin (5
      Fu/Lv), and randomly assigned patients to start with either of the two. METHODS:
      Patients with previously untreated locally advanced or metastatic GC and with
      measurable lesions (response evaluation criteria in solid tumors; RECIST) were
      randomly assigned to start with docetaxel 45 mg/m(2) (arm T) or irinotecan 180
      mg/m(2) (arm C) with bolus/44-h infusion of 5-Fu/Lv (day 1 every 2 weeks). After
      four courses, there was a prescheduled crossover to the alternative regimen for
      four additional courses. RESULTS: Eighty-one patients were randomized and 78
      started treatment. Complete and partial responses were seen in 31 (40%) patients
      after 8 weeks and in 32 (41%) after 16 weeks, with similar results in both study
      arms. The median overall survival (OS) was 11.5 and 10.6 months in arms T and C,
      respectively (P = 0.3). The two schedules were feasible and did not differ in the
      overall rate of severe adverse events (SAEs). CONCLUSION: This is the first
      randomized comparison of two of the newer cytostatic drugs in GC therapy. No
      differences favoring either arm T or arm C were found with respect to response
      rate, OS, or toxicity. The median OS of 11 months indicates that sequential
      administration of the two combinations is effective and is similar to triple
      combinations. Thus, comparable efficacy to platinum combinations appears to be
      obtained with newer, less toxic regimens when given sequentially.

PMID- 20820985
TI  - The detection of Helicobacter pylori cag pathogenicity islands (PAIs) and
      expression of matrix metalloproteinase-7 (MMP-7) in gastric epithelial dysplasia
      and intramucosal cancer.
AB  - BACKGROUND: The cag pathogenicity island (PAI), a Helicobacter pylori virulence
      factor, is associated with the pathogenesis of gastric cancer. Matrix
      metalloproteinase-7(MMP-7) is upregulated in the epithelial cells of gastric
      cancer. To date, there is limited information available on the role of cag PAI
      and MMP-7 in precursor lesions. In this study, we aimed to identify virulent H.
      pylori strains and the expression of MMP-7 in samples of gastric epithelial
      dysplasia and intramucosal cancer. METHODS: One hundred and twelve tissues
      excised by endoscopic mucosal resection, 76 specimens with gastric epithelial
      dysplasia and 36 with intramucosal cancer, were examined. All tissue samples were
      paired with surrounding normal epithelial tissue samples. We performed polymerase
      chain reaction for cagA and cagL in neoplasia and paired normal specimens, and
      assessed the matrix metalloproteinase (MMP)-7 expression by immunohistochemical
      staining. RESULTS: There was a significant difference in the frequencies of cagA
      or cagL between specimens with gastric dysplasia and those with intramucosal
      cancer. We confirmed greater expression of MMP-7 immunoreactivity in intramucosal
      cancers infected with a virulent H. pylori strain. CONCLUSION: Our results
      suggest that infection with a virulent H. pylori strain was associated with early
      stage gastric cancer and that carcinogenesis was associated with cag PAI
      dependent MMP-7 upregulation.

PMID- 20820986
TI  - High preoperative neutrophil-lymphocyte ratio predicts poor survival in patients
      with gastric cancer.
AB  - BACKGROUND: The neutrophil-lymphocyte ratio (NLR) reflects inflammatory status.
      An elevated NLR has been reported to be a prognostic indicator in some malignant
      tumors. The aim of this study was to evaluate the clinical significance of the
      preoperative NLR in patients with primary gastric cancer. METHODS: A total of 709
      men and 319 women, with a mean age of 64.4 years, who underwent gastrectomy were
      included. The numbers of patients in each pathological stage were as follows:
      stage I, 584; stage II, 132; stage III, 153; and stage IV, 159. The mean NLR was
      2.62 +/- 1.68. A total of 127 patients (12.4%) with an NLR of 4.0 or more were
      classified as high NLR individuals in this study. The prognostic significance of
      a high NLR, together with various clinicopathological factors, was evaluated by
      multivariate analysis. RESULTS: The 5-year survival of patients with a high NLR
      was significantly worse than that of patients with a low NLR (57% vs 82%, P <
      0.001). Univariate and multivariate analyses of clinicopathological factors
      affecting survival revealed that high NLR, depth of tumor, positive lymph nodes,
      distant metastasis, peritoneal metastasis, poorly differentiated type, and high
      platelet count were significant risk factors for reduced survival. On
      multivariate analysis, after adjusting for tumor stage, a high NLR was an
      independent risk factor for reduced survival (P = 0.003; adjusted hazard ratio,
      1.845; 95% confidence interval, 1.236-2.747). CONCLUSION: A high preoperative NLR
      may be a convenient biomarker to identify patients with a poor prognosis after
      resection for primary gastric cancer.

PMID- 20820987
TI  - Geminin, Ki67, and minichromosome maintenance 2 in gastric hyperplastic polyps,
      adenomas, and intestinal-type carcinomas: pathobiological significance.
AB  - BACKGROUND: Geminin negatively regulates Cdt1 and induces the formation of
      prereplicative complexes by loading mini-chromosome maintenance proteins (Mcm)
      onto chromatin and limiting DNA replication to once per cell cycle. Recent
      studies have suggested that geminin expression is a marker of the S/G2/M phase of
      the cell cycle and is associated with a poor prognosis in various human
      malignancies. This study aimed to clarify the pathobiological role of geminin in
      intestinal-type gastric carcinoma, and its relationships with minichromosome
      maintenance 2 (Mcm2) and Ki67 expression. METHODS: We performed western blot
      analysis of seven human gastric cancer cell lines, and immunohistochemical
      analysis of 72 gastric mucosal lesions and 128 surgically removed advanced
      intestinal-type gastric carcinomas. Double-labeling immuno-fluorescence was
      performed to identify the coexpression of geminin and Ki67. RESULTS: Geminin was
      detected in all cell lines. Geminin labeling indices (LIs) in hyperplastic
      polyps, low-grade adenomas, high-grade adenomas, and intestinal-type
      adenocarcinomas were 3.9%, 10.5%, 18.6%, and 27.2%, respectively. The equivalent
      LIs for Ki67 and Mcm2 were 17.7%, 42.2%, 52.6%, and 59.7%; and 26.7%, 70.0%,
      67.8%, and 77.8%, respectively. Double-labeling immunofluorescence revealed
      coexpression of geminin and Ki67 in both normal and tumor cells. The LI for
      geminin was significantly correlated with N stage, International Union Against
      Cancer (UICC) stage, Mcm2 LI, and Ki67 LI. Patients in stages I-IV and stage III
      with higher LIs for geminin (>25%) had significantly worse prognoses (P < 0.05
      and P < 0.04, respectively). Univariate Cox regression analysis indicated that
      the overall survival of stage I-IV tumors was significantly correlated with high
      geminin LIs (relative risk [RR] = 1.94; P = 0.04). CONCLUSIONS: Geminin
      expression might reflect the biological nature of gastric intramucosal neoplasms
      and could be a possible prognostic marker in advanced intestinal-type gastric
      carcinomas.

PMID- 20820988
TI  - Second-line chemotherapy with irinotecan plus cisplatin after the failure of S-1
      monotherapy for advanced gastric cancer.
AB  - BACKGROUND: For advanced gastric cancer (AGC), second-line chemotherapy after the
      failure of S-1 has not yet been established. The present study aimed to
      retrospectively evaluate the efficacy and safety of irinotecan plus cisplatin
      (IP) therapy after the failure of S-1 in patients with AGC. METHODS: The subjects
      included 87 patients with AGC who received IP therapy as second-line
      chemotherapy. Irinotecan (70 mg/m(2)) was administered by intravenous infusion
      followed by an intravenous infusion of cisplatin (80 mg/m(2)) on day 1. On day
      15, irinotecan (70 mg/m(2)) alone was administered. The treatment was repeated
      every 4 weeks until disease progression, patient refusal, or severe adverse
      events. RESULTS: The median patient age was 62 years (range, 39-75 years), and
      the median number of treatment cycles was 3 (range, 1-9). Out of the 87 patients,
      70 were assessable for clinical response. There were 2 complete responses and 18
      partial responses. The overall response rate was 28.6% (95% confidence interval
      [CI], 18.4%-40.6%) and the disease control ratio was 70.0%. The median time to
      progression and median survival time from the first day of IP therapy were 4.3
      months and 9.4 months, respectively. The 1-year survival rate was 34.6%. Severe
      (grade 3/4) leukopenia, neutropenia, anemia, and thrombocytopenia were observed
      in 34%, 40%, 28%, and 8% of patients, respectively. Grade 3/4 nonhematologic
      toxicities included anorexia (17%), febrile neutropenia (10%), diarrhea (6%),
      fatigue (5%), nausea (2%), and elevated creatinine (1%). CONCLUSIONS: The
      combination of irinotecan plus cisplatin as second-line chemotherapy for AGC
      appears to be an effective and feasible treatment option after S-1 failure.

PMID- 20820989
TI  - The prognostic significance of isolated tumor cells in the lymph nodes of gastric
      cancer patients.
AB  - BACKGROUND: The clinical significance of isolated tumor cells (ITC) detected
      immunohistochemically in the lymph nodes of gastric cancer patients is
      controversial. The aim of this study was to examine the prognostic impact of ITC
      in patients with gastric cancer. METHODS: The data of a total of 402 patients
      with pathological T2N0 and T2N1 gastric cancer who underwent gastrectomy with D2
      lymph node dissection between 1984 and 1990 at four participant hospitals were
      analyzed. All resected lymph nodes were reexamined by serial sectioning with
      hematoxylin & eosin (H&E) staining, and evaluated by immunohistochemistry using
      antibody against cytokeratin (AE1/3). The prevalence and prognostic significance
      of ITC were investigated. RESULTS: ITC were detected in 187 of the 402 (47%)
      patients. A multivariate analysis identified the nodal status, histological type,
      and tumor size as significant factors predictive of the presence/absence of ITC.
      The 5-year and 10-year overall survival rates of patients with vs those without
      ITC were 84.4% (95% confidence interval [CI], 79.1-89.0) and 70.4% (95% CI, 64.1
      76.7) vs 83.9% (95% CI, 78.6-89.2) and 72.0% (95% CI, 65.4-78.5), respectively.
      The hazard ratio for death in patients with ITC as compared with those without
      ITC was 0.90 (95% CI, 0.64-1.26; P = 0.53). CONCLUSIONS: The presence of ITC in
      the lymph nodes does not affect the prognosis of patients with gastric cancer who
      have undergone gastrectomy with D2 lymph node dissection.

PMID- 20820990
TI  - A feasibility study of postoperative chemotherapy with S-1 and cisplatin (CDDP)
      for gastric carcinoma (CCOG0703).
AB  - BACKGROUND: The outcome of stage III gastric cancer patients treated by D2
      dissection followed by adjuvant chemotherapy with S-1 remains unsatisfactory.
      Moreover, some patients with a preoperative diagnosis of stage II/III turn out to
      be stage IV after surgical exploration, and a standard postoperative treatment
      for this population has not been established. METHODS: A feasibility study of
      postoperative S-1/cisplatin (CDDP) was performed with patients who underwent
      gastrectomy for what turned out to be a stage IV gastric cancer. The primary
      endpoint of the trial was the relative dose intensity during five courses of S
      1/CDDP. Several criteria to skip, postpone, or reduce the dose had been
      predetermined. RESULTS: Between 2007 and 2009, 31 patients were accrued,
      including 19 patients who were positive for peritoneal washing cytology, 6 with
      peritoneal seeding, 5 with metastasis to the paraaortic nodes, and 4 with other
      distant metastases. Only 7 patients completed five cycles as planned (median, two
      cycles). The median relative dose intensities of S-1 and CDDP were 37% and 40%,
      respectively. Causes of treatment failure were failure to fulfill criteria for
      starting a new course within 5 weeks of the last administration of S-1 in 7,
      patient refusal in 6, disease recurrence/progression in 4, need to reduce dose by
      two levels in 4, and two successive skips of CDDP in 3 patients. The median
      progression-free survival time of all patients was 363 days. CONCLUSIONS:
      Although promising in the neoadjuvant and advanced/metastatic setting, S-1/CDDP
      is too toxic as a postgastrectomy treatment for Japanese patients.

PMID- 20820991
TI  - Paraneoplastic neurological syndrome in a patient with gastric cancer.
AB  - Paraneoplastic neurological syndromes (PNSs) are a heterogeneous group of
      neurological disorders caused by immune-mediated mechanisms. The incidence of PNS
      is much less than 1% for solid tumors, except for small-cell lung cancer and
      thymoma. We report a rare case of gastric cancer that presented with primary
      clinical findings of PNS. The patient was a 63-year-old woman who was admitted
      for worsening neuropathy. Laboratory and neurological tests excluded a
      nutritional deficit, diabetes mellitus, and connective tissue disease as causes
      of her neuropathy. Computed tomography (CT) of the abdomen, positron emission
      tomography (PET)-CT, and endoscopy of the stomach revealed gastric cancer with
      lymph node swelling. Distal gastrectomy was performed and pathological and
      immunohistochemical examinations indicated endocrine cell carcinoma. The
      gastrectomy stopped the exacerbation of her symptoms and recurrence was not
      observed, but the neurological disorders were irreversible. This case suggests
      that early diagnosis of the primary tumor is required to improve the outcome in
      patients with PNS.

PMID- 20820993
TI  - Behavior of polysaccharide assemblies in field-flow fractionation and size
      exclusion chromatography.
AB  - Asymmetric flow field-flow fractionation (AsFlFFF) and high-performance size
      exclusion chromatography (HPSEC) are techniques for separating and characterizing
      macromolecules; until now the latter is more utilized for analyzing
      polysaccharides. The demand for characterizing complex, high-molar-mass
      polysaccharides has raised interest in the use of AsFlFFF in analyzing polymeric
      carbohydrates in addition to HPSEC. In this paper, we compare the behavior of
      arabinoxylan aggregates present in aqueous solution in AsFlFFF and HPSEC and
      their effect on the obtained molecular characteristics (molar mass averages and
      size). Although the amount of aggregates in aqueous arabinoxylan solutions may be
      low, their role needs to be understood to avoid erroneous interpretations of
      AsFlFFF and HPSEC data. When these two separation systems were compared, AsFlFFF
      seemed to possess more separation power for the differentiation of aggregates
      from individual chains than HPSEC. To our knowledge, this is the first report on
      the characterization of xylans with AsFlFFF.

PMID- 20820992
TI  - Phosphorylation mechanisms in intensive care medicine.
AB  - INTRODUCTION: The phosphorylation states of proteins, lipids, carbohydrates,
      amino acids, and nucleotides control the mechanisms behind nearly all cellular
      functions. Therefore, not surprisingly, recent findings have shown that
      alterations in these phosphorylation pathways play a central role in the
      development and progression of many disease states. This review provides a brief
      summary of the function and activity of various phosphorylation mechanisms,
      outlines some of the major phosphorylation signaling cascades, and describes the
      role of these phosphorylation mechanisms in intensive care medicine. METHODS:
      This article will comprise a comprehensive review of the literature in the
      context of intensive care medicine. Specifically, we will discuss the involvement
      of phosphorylation in the pathogenesis, diagnosis, and treatment of heart
      failure, myocardial infarction, stroke, respiratory failure, ventilation-induced
      lung injury, traumatic brain injury, acute organ failure, systemic sepsis, and
      shock. CONCLUSION: Phosphorylation mechanisms clearly play an important role in
      many pathologies and treatment strategies of intensive care and therefore further
      understanding of these mechanisms may lead to the development of novel therapies
      and improved patient care.

PMID- 20820994
TI  - Analysis of methotrexate and its eight metabolites in cerebrospinal fluid by
      solid-phase extraction and triple-stacking capillary electrophoresis.
AB  - We establish a triple-stacking capillary electrophoresis (CE) separation method
      to monitor methotrexate (MTX) and its eight metabolites in cerebrospinal fluid
      (CSF). Three stacking methods with different mechanisms were combined and
      incorporated into CE separation. Complete stacking and sharp peaks were achieved.
      Firstly, the optimized buffer (60 mM phosphate containing 15% THF and 100 mM SDS)
      was filled into the capillary, which was followed by the higher conductivity
      buffer (100 mM phosphate, 2 psi for 45 s). The analytes extracted from CSF were
      injected at 2 psi for 99.9 s, which provided long sample zones and pH junction
      for focusing. Finally, the stacking step was performed by sweeping, and
      separation was achieved by micellar electrokinetic chromatography. The results of
      the linear regression equations indicated high linearity (r >= 0.9981) over the
      range of 0.5-7 MUM. In intra- and inter-batch results, all data of RSD and RE
      were below 11%, indicating good precision and accuracy of this method. The LODs
      (S/N = 3) were 0.1 MUM for MTX, 7-hydroxymethotrexate (7-OHMTX) and MTX
      polyglutamates (MTX-(Glu)(n, n = 2-5)), 0.2 MUM for MTX-(Glu)(6), and 0.3 MUM for
      2,4-diamino-N(10)-methylpteroic acid (DAMPA) and MTX-(Glu)(7). Our method was
      implemented for analysis of MTX and its metabolites in the CSF, and could be used
      for evaluation of its curative effects of acute lymphoblastic leukemia patients.
      The data were also confirmed by matrix-assisted laser desorption ionization time
      of-flight mass spectrometry. The results showed good coincidence.

PMID- 20820995
TI  - Application of ion mobility spectrometry for the detection of human urine.
AB  - The aim of the present study was to evaluate the suitability of ion mobility
      spectrometry (IMS) for the detection of human urine as an indication of human
      presence during urban search and rescue operations in collapsed buildings. To
      this end, IMS with a radioactive ionization source and a multicapillary column
      was used to detect volatile organic compounds (VOCs) emitted from human urine. A
      study involving a group of 30 healthy volunteers resulted in the selection of
      seven volatile species, namely acetone, propanal, 3-methyl-2-butanone, 2
      methylpropanal, 4-heptanone, 2-heptanone and octanal, which were detected in all
      samples. Additionally, a preliminary study on the permeation of urine volatiles
      through the materials surrounding the voids of collapsed buildings was performed.
      In this study, quartz sand was used as a representative imitating material. Four
      compounds, namely 3-methyl-2-butanone, octanal, acetone and 2-heptanone, were
      found to permeate through the sand layers during all experiments. Moreover, their
      permeation times were the shortest. Although IMS can be considered as a potential
      technique suitable for the detection, localization and monitoring of VOCs evolved
      from human urine, further investigation is necessary prior to selecting field
      chemical methods for the early location of trapped victims.

PMID- 20820996
TI  - Distribution and metabolism of selenohomolanthionine labeled with a stable
      isotope.
AB  - The distribution and metabolism of selenohomolanthionine (4,4'-selenobis[2
      aminobutanoic acid], SeHLan), a newly identified selenoamino acid in selenized
      Japanese pungent radish, were evaluated by administering 77Se-labeled SeHLan at a
      dose of 25 MUg/kg body weight in rats. Exogenous 77Se of SeHLan was preferably
      distributed to the kidneys and remained in the intact form for up to 6 h after
      dosing. The accumulation in the kidneys is one of the specific characteristics of
      SeHLan, differing from other selenoamino acids, such as selenomethionine and Se
      methylselenocysteine, which preferably accumulate in the pancreas. The intact
      form of SeHLan was detected in the serum and kidney supernatant but not in the
      urine, suggesting that the amount of exogenous Se that was distributed to the
      kidneys was within metabolic capacity. Indeed, the exogenous Se was converted
      into two urinary metabolites, Se-methylseleno-N-acetyl-galactosamine and
      trimethylselenonium. Exogenous Se was also detected in several selenoproteins,
      including selenoprotein P and extracellular glutathione peroxidase. SeHLan is
      expected to be a potential supplemental source of Se because its distribution
      differs from that of selenomethionine and Se-methylselenocysteine.

PMID- 20820997
TI  - Matrix-free and material-enhanced laser desorption/ionization mass spectrometry
      for the analysis of low molecular weight compounds.
AB  - The application of matrix-assisted laser desorption/ionization (MALDI) mass
      spectrometry (MS) for the analysis of low molecular weight (LMW) compounds, such
      as pharmacologically active constituents or metabolites, is usually hampered by
      employing conventional MALDI matrices owing to interferences caused by matrix
      molecules below 700 Da. As a consequence, interpretation of mass spectra remains
      challenging, although matrix suppression can be achieved under certain
      conditions. Unlike the conventional MALDI methods which usually suffer from
      background signals, matrix-free techniques have become more and more popular for
      the analysis of LMW compounds. In this review we describe recently introduced
      materials for laser desorption/ionization (LDI) as alternatives to conventionally
      applied MALDI matrices. In particular, we want to highlight a new method for LDI
      which is referred to as matrix-free material-enhanced LDI (MELDI). In matrix-free
      MELDI it could be clearly shown, that besides chemical functionalities, the
      material's morphology plays a crucial role regarding energy-transfer
      capabilities. Therefore, it is of great interest to also investigate parameters
      such as particle size and porosity to study their impact on the LDI process.
      Especially nanomaterials such as diamond-like carbon, C(60) fullerenes and
      nanoparticulate silica beads were found to be excellent energy-absorbing
      materials in matrix-free MELDI.

PMID- 20820998
TI  - GC/MS detection of central nervous tissues as specified BSE risk material in meat
      products: validation by an externally controlled blind trial.
AB  - The addition of central nervous tissues (CNT), such as brain and spinal cord, in
      the manufacturing of meat products is either forbidden--if the material falls
      under the legal definition of specified risk material (SRM)--or must be labelled
      on the packed product. To foster official food control, several CNT detection
      methods were developed, but only fatty acid patterns as detected by gas
      chromatography/mass spectrometry (GC/MS) allow the further characterization of
      the detected CNT as to both the animal species and--surprisingly--the age of the
      animal from which the CNT was derived in accordance with the legal definition.
      Complementing a previous report in this journal by Lucker et al. 2010 (doi:
      10.1007/s00216-010-3956-5) on CNT quantification by GC/MS, we now report results
      of the validation of this new analytical approach by an externally controlled
      blind trial elucidating its potential to identify the species and age of the CNT
      detected. The 72 samples (24 standards of emulsion-type sausage, each heated in
      three different batches: 75 degrees C, 30 min; 115 degrees C, 25 min; 133 degrees
      C, 40 min) containing porcine, ovine or bovine muscle tissue and differing
      amounts of CNT (bovine or ovine brain: 0, 0.1, 0.5, 1.0, 3.0% m/m) were produced
      externally and provided blind for analyses to our laboratory. In accordance with
      the previous study, heating had no detectable effect on the GC/MS analysis.
      Judged by the present sensitivity of this method (cut-off 0.2% CNT), all of the
      samples containing 0.5% or more CNT (n = 57, 100%) were identified correctly as
      CNT-positive. The CNT species was identified correctly in 54 samples (94.7%),
      with three samples of one specific standard (0.5% ovine CNT) falsely classified
      as bovine CNT. However, the CNT age of these samples was correctly classified
      (more than 12 months). Overall, 57 samples (100%) were correctly classified as
      SRM-positive and 15 samples (100%) as SRM-negative. To the best of our knowledge,
      this is the first time that a legal demand for the (1) detection of traces of a
      specific tissue in a food matrix, (2) the identification of its taxonomic origin
      and (3) the classification of its age has been shown to be analytically possible
      in totally blind samples. The very positive validation results of this externally
      controlled blind trial recommend the present GC/MS approach for the detection of
      CNT in meat products as a reference method. However, our results also demonstrate
      the need for further studies, in particular to increase sensitivity and to
      conduct ring trials including more than one laboratory.

PMID- 20820999
TI  - Selective recognition of a saccharide-type tumor marker with natural and
      synthetic ligands: a new trend in cancer diagnosis.
AB  - It is well known that saccharides and their glycoconjugates can have an important
      influence on various serious pathologic stages such as cancer. They can regulate
      tumor proliferation, invasion, hematogenous metastasis, and angiogenesis. These
      facts clearly show the importance of cancer saccharide recognition. In medicine,
      sensor analysis is one of the best methods for recognition and determination of
      biologically important analytes. The development and study of sensors for
      saccharide tumor markers can open a new way for their detection. Therefore, this
      review is focused on recognition of saccharide-based cancer markers by natural or
      synthetic selective ligands working as bio- and chemosensors. The design and
      application of these ligands for cancer diagnosis is a useful direction of
      research. Moreover, it also opens the possibility of using these agents for the
      targeted drug transport required for advanced anticancer therapy.

PMID- 20821000
TI  - Analytical potential of hybrid nanoparticles.
AB  - The growing use of nanoparticles in the analytical process in recent years has
      set a new trend towards the simplification of analytical methods and improvement
      of their performance. Miniaturization and nanotechnology have allowed new
      analytical challenges to be met. Hybrid nanoparticles in particular possess
      exceptional properties enabling further improvement of analytical methods.
      Despite the continuous developments in their synthesis and characterization,
      hybrid nanomaterials have scarcely been used in analytical chemistry, however.
      This paper discusses the analytical potential of hybrid nanoparticles in terms of
      their special characteristics and properties, and describes their analytical
      applications.

PMID- 20821001
TI  - Several conserved positively charged amino acids in OATP1B1 are involved in
      binding or translocation of different substrates.
AB  - OATP1B1 and 1B3 are related transporters mediating uptake of numerous compounds
      into hepatocytes. A putative model of OATP1B3 with a "positive binding pocket"
      containing conserved positively charged amino acids was predicted (Meier-Abt et
      al. J Membr Biol 208:213-227, 2005). Based on this model, we tested the
      hypothesis that these positive amino acids are important for OATP1B1 function. We
      made mutants and measured surface expression and uptake of estradiol-17beta
      glucuronide, estrone-3-sulfate and bromosulfophthalein in HEK293 cells. Two of
      the mutants had low surface expression levels: R181K at 10% and R580A at 30% of
      wild-type OATP1B1. A lysine at position 580 (R580K) rescued the expression of
      R580A. Mutations of several amino acids resulted in substrate-dependent effects.
      The largest changes were seen for estradiol-17beta-glucuronide, while estrone-3
      sulfate and bromosulfophthalein transport were less affected. The wild-type
      OATP1B1 K (m) value for estradiol-17beta-glucuronide of 5.35 +/- 0.54 MUM was
      increased by R57A to 30.5 +/- 3.64 MUM and decreased by R580K to 0.52 +/- 0.18
      MUM. For estrone-3-sulfate the wild-type high-affinity K (m) value of 0.55 +/-
      0.12 MUM was increased by K361R to 1.8 +/- 0.47 MUM and decreased by R580K to 0.1
      +/- 0.04 MUM. In addition, R580K reduced the V (max) values for all three
      substrates to <25% of wild-type OATP1B1. Mutations at intracellular K90, H92 and
      R93 mainly affected V (max) values for estradiol-17beta-glucuronide uptake. In
      conclusion, the conserved amino acids R57, K361 and R580 seem to be part of the
      substrate binding sites and/or translocation pathways in OATP1B1.

PMID- 20821002
TI  - Modulatory effects of natural curcuminoids on P-glycoprotein ATPase of
      insecticide-resistant pest Helicoverpa armigera (Lepidopetera: Noctuidae).
AB  - Three major curcuminoids (I, II and III) were purified from turmeric and tested
      for their ability to modulate the function of P-glycoprotein ATPase of the
      insecticide-resistant pest Helicoverpa armigera (Ha-Pgp). The curcumin mixture
      inhibited the activity of Ha-Pgp ATPase by 80-90% at 100 MUM concentration. Along
      with curcuminoids I, II and III, it inhibited the verapamil- and ethylparaoxon
      stimulated Ha-Pgp ATPase activity. Curcuminoid binding was quantitated by
      quenching the intrinsic Trp fluorescence of purified Ha-Pgp ATPase. Transport was
      monitored in proteoliposomes containing Ha-Pgp ATPase using the high-affinity
      fluorescent substrate tetramethylrosamine (TMR) in real time. Addition of the
      curcuminoid mixture collapsed the TMR concentration gradient generated by Ha-Pgp
      ATPase. Inhibition studies on Ha-Pgp ATPase activity are important to develop
      strategies to overcome insecticide resistance in this pest.

PMID- 20821003
TI  - Osteonecrosis in an adolescent with non-Hodgkin lymphoma resembling a new
      metastatic lesion on (18)F-FDG PET/CT.
AB  - Osteonecrosis may result from complications in a variety of pediatric diseases
      and, in the early stages of healing, may be characterized by inflammation and
      hyperemia. While traditionally assessed by bone scintigraphy, osteonecrosis may
      also present upon [F-18]2-fluoro-2-deoxyglucose PET/CT. Differentiation of
      osteonecrosis from metastatic lesions is important to ensure accurate disease
      staging and to avoid unnecessary imaging and biopsy. Osteonecrosis typically
      presents at the interface of weight-bearing joints after prolonged chemotherapy
      with corticosteroid administration, although prevalence is greater in adults than
      in children. We describe a case of unilateral osteonecrosis in the tibia of an
      adolescent lymphoma patient, which first presented on FDG-PET/CT imaging after 2
      months of combination chemotherapy with corticosteroid administration. This
      report should aid in recognizing rapid-onset osteonecrosis with atypical sites of
      involvement in pediatric patients.

PMID- 20821004
TI  - Minisymposium: molecular imaging.

PMID- 20821005
TI  - Radiation dose for thoracic and coronary step-and-shoot CT using a 128-slice dual
      source machine in infants and small children with congenital heart disease.
AB  - BACKGROUND: For coronary artery visualization, retrospective ECG-gated
      acquisition by dual-source computed tomography (DSCT) was superior to spiral non
      ECG-gated acquisition in a paediatric population of congenital heart disease
      (CHD) patients. However, retrospective cardiac CT is associated with substantial
      radiation doses to the patient. Recently, DSCT with end-systolic reconstruction
      was found to be robust for imaging the coronary arteries in patients with high
      heart rates. OBJECTIVE: To evaluate step-and-shoot DSCT with end-systolic
      reconstruction for evaluating the heart, coronary arteries and other thoracic
      structures in young children with CHD. MATERIALS AND METHODS: All neonates and
      children younger than 6 years of age who were referred to our institution for CHD
      evaluation between September and October 2009 were included in the study. ECG
      gated DSCT was performed in sequential prospective mode centred on the systolic
      phase identified by ECG analysis. To assess the radiation dose, we recorded the
      dose-length product (DLP) in mGy.cm and the effective dose in mSv estimated from
      the DLP. Overall image quality was evaluated using a 5-grade scoring system and
      was assessed by looking at cardiac and vascular structures. The image quality for
      the proximal and middle segments of the right and left coronary arteries was also
      evaluated using a 5-grade scale. RESULTS: Images of diagnostic quality (grade >=
      3) were obtained in all 30 children with a mean image quality grade of 4.7 +/-
      0.6 (range, 3-5). Mean DLP was 5.7 +/- 4.8 mGy*cm (range, 1-22 mGy cm) and mean
      effective radiation dose was 0.26 +/- 0.16 mSv (range, 0.05-0.8 mSv). CONCLUSION:
      Prospective ECG-gated thoracic DSCT at end-systole usually provides adequate
      thoracic and coronary artery image quality in neonates, infants and young
      children with CHD, independent of heart rate. This new method is associated with
      lower radiation doses compared to previous literature (mean effective dose, 0.26
      mSv).

PMID- 20821006
TI  - Reduced coronary flow reserve in patients with primary hyperparathyroidism: a
      study by G-SPECT myocardial perfusion imaging.
AB  - PURPOSE: The mechanisms underlying increased cardiovascular risk in primary
      hyperparathyroidism (pHPT) have not been fully defined. Recently, this issue has
      become the subject of renewed interest due to the increasing evidence that the
      endothelium and vascular wall are targets for parathyroid hormone (PTH). The aim
      of this study was to measure regional coronary flow reserve (CFR) to determine
      whether the vascular damage induced by pHPT extends to affect the coronary
      microvascular function. METHODS: A total of 22 pHPT patients without a history of
      coronary artery disease and 7 age-matched control subjects were recruited.
      Dipyridamole myocardial blood flow (MBF) was assessed using 99mTc-sestamibi by
      measuring first-transit counts in the pulmonary artery and myocardial count rate
      from G-SPECT images. Baseline MBF was estimated 2 h later according to the same
      procedure. Regional CFR was defined as the ratio between dipyridamole and
      baseline MBF using a 17-segment left ventricular model. RESULTS: Three pHPT
      patients showed reversible perfusion defects and were excluded from the analysis.
      In the remaining 19, CFR was significantly lower with respect to the control
      subjects (1.88+/-0.64 vs. 3.36+/-0.66, respectively; p<0.01). Moreover, patients
      studied for more than 28 months from pHPT diagnosis showed lower CFR values than
      the others (1.42+/-0.18 vs. 2.25+/-0.64, respectively; p<0.01). Consequently, the
      time from diagnosis to the nuclear study showed a reasonable correlation with the
      degree of CFR impairment (Spearman's rho -0.667, p<0.02). CONCLUSION: pHPT is
      associated with a significant dysfunction of the coronary microcirculation. This
      disorder might contribute to the high cardiovascular risk of conditions
      characterized by chronic elevations in serum PTH levels.

PMID- 20821007
TI  - Methodological issues in the evaluation of FDG PET/CT accuracy in pediatric
      lymphoma.

PMID- 20821008
TI  - A comparison of primary and secondary rhytidectomy results.
AB  - BACKGROUND: This study aimed to evaluate the authors' surgical experience with
      secondary rhytidectomy and to compare these results with those for primary
      rhytidectomy patients. METHODS: A retrospective review of patients who had
      undergone secondary rhytidectomy was performed. In addition, an equivalent number
      of primary rhytidectomy patients were selected randomly. Data were collected
      evaluating patient age, time elapsed between rhytidectomies, type of procedure
      performed, superficial musculoaponeurotic system (SMAS) thickness, amount of skin
      resected, complications, adjunctive procedures, and patient satisfaction.
      RESULTS: This study enrolled 21 secondary rhytidectomy patients. The average time
      elapsed between their previous and last rhytidectomy was 9.95 years. Using a
      grading scale of -4 to 4, the average SMAS thickness was 2.2 for the primary and
      0.67 for the secondary rhytidectomy patients. The average skin resection was 26.6
      mm for the primary and 17.6 mm for the secondary rhytidectomy patients. The
      complications for secondary rhytidectomy included one hematoma and one
      hypertrophic postauricular scar. The follow-up period ranged from 6 months to 7
      years. All secondary rhytidectomy patients expressed satisfaction with their
      overall aesthetic result. CONCLUSIONS: Secondary rhytidectomy is a safe and
      effective procedure for the aging face. The SMAS of older patients appears to be
      thinner and more delicate and therefore must be handled with care. Additionally,
      skin resection is significantly reduced compared with that for primary
      rhytidectomy patients.

PMID- 20821010
TI  - Selecting sites for converting farmlands to wetlands in the Sanjiang Plain,
      Northeast China, based on remote sensing and GIS.
AB  - Wetlands in the Sanjiang Plain are rich in biodiversity and natural resources in
      the northeast of China. However, this wetland area has decreased in size and
      deteriorated in quality owing to expanded agricultural activities since the
      1950s. Converting farmlands to wetlands is necessary to improve these conditions.
      Using Remote Sensing (RS) and Geographic Information Systems (GIS) technologies,
      we derived farmland productivity data and hydrology data for the Sanjiang Plain.
      The farmland productivity data were derived from land use and net primary
      productivity (NPP) data of the MODIS products. We obtained three productivity
      farmland classes (low, medium, and high) through the NPP anomaly percentage
      method. We were only concerned with the low-productivity farmland. Hydrology data
      were modeled with a wetness index, which was derived from Digital Elevation Model
      (DEM) data. Based on these two data layers, we identified and prioritized sites
      for the conversion of farmlands to wetlands. The areas with low farmland
      productivity and medium or high wetness values have potential to support the
      conversion of farmlands to wetlands. Potential sites were prioritized in terms of
      patch size and proximity to natural wetlands and water bodies. We obtained three
      priority classes, among which the high-priority class would be used as the areas
      for the recent conversion of farmlands to wetlands. The area of this class was
      75,888 ha and accounted for 1.3% of the total farmland area.

PMID- 20821009
TI  - In situ burning restores the ecological function and structure of an oil-impacted
      coastal marsh.
AB  - As the use of in situ burning for oil spill remediation in coastal wetlands
      accelerates, the capacity of this procedure to restore the ecological structure
      and function of oil-impacted wetlands becomes increasingly important. Thus, our
      research focused on evaluating the functional and structural recovery of a
      coastal marsh in South Louisiana to an in situ burn following a Hurricane Katrina
      induced oil spill. Permanent sampling plots were set up to monitor marsh recovery
      in the oiled and burned areas as well as non-oiled and non-burned (reference)
      marshes. Plots were monitored for species composition, stem density, above- and
      belowground productivity, marsh resiliency, soil chemistry, soil residual oil,
      and organic matter decomposition. The burn removed the majority of the oil from
      the marsh, and structurally the marsh recovered rapidly. Plant biomass and
      species composition returned to control levels within 9 months; however, species
      richness remained somewhat lower in the oiled and burned areas compared to the
      reference areas. Recovery of ecological function was also rapid following the in
      situ burn. Aboveground and belowground plant productivity recovered within one
      growing season, and although decomposition rates were initially higher in the
      oiled areas, over time they became equivalent to those in reference sites. Also,
      marsh resiliency, i.e., the rate of recovery from our applied disturbances, was
      not affected by the in situ burn. We conclude that in situ burning is an
      effective way to remove oil and allow ecosystem recovery in coastal marshes.

PMID- 20821011
TI  - Aggressive LGL leukaemia presentation in old age.

PMID- 20821012
TI  - Proliferation and differentiation potential of CD133+ and CD34+ populations from
      the bone marrow and mobilized peripheral blood.
AB  - CD34 is the most frequently used marker for the selection of cells for bone
      marrow (BM) transplantation. The use of CD133 as an alternative marker is an open
      research topic. The goal of this study was to evaluate the proliferation and
      differentiation potential for hematopoiesis (short and long term) of CD133+ and
      CD34+ populations from bone marrow and mobilized peripheral blood. Eight cell
      populations were compared: CD34+ and CD133+ cells from both the BM (CML Ph-, CML
      Ph+, and healthy volunteers) and mobilized peripheral blood cells. Multicolor
      flow cytometry and cultivation experiments were used to measure expression and
      differentiation of the individual populations. It was observed that the CD133+ BM
      population showed higher cell expansion. Another finding is that during a 6-day
      cultivation with 5(6)-carboxyfluorescein diacetate N-succinimidyl ester (CFSE),
      more cells remained in division D0 (non-dividing cells). There was a higher
      percentage of CD38- cells observed on the CD133+ BM population. It was also
      observed that the studied populations contained very similar but not the same
      pools of progenitors: erythroid, lymphoid, and myeloid. This was confirmed by CFU
      GM and CFU-E experiments. The VEGFR antigen was used to monitor subpopulations of
      endothelial sinusoidal progenitors. The CD133+ BM population contained
      significantly more VEGFR+ cells. Our findings suggest that the CD133+ population
      from the BM shows better proliferation activity and a higher distribution of
      primitive progenitors than any other studied population.

PMID- 20821013
TI  - Additional benefit of 18F-fluorodeoxyglucose integrated positron emission
      tomography/computed tomography in the staging of oesophageal cancer.
AB  - OBJECTIVE: 18F-fluorodeoxyglucose positron emission tomography (FDG PET) has been
      shown to improve the accuracy of staging in oesophageal cancer. We assessed the
      benefit of PET/CT over conventional staging and determined if tumour histology
      had any significant impact on PET/CT findings. METHODS: A retrospective cohort
      study, reviewing the results from 200 consecutive patients considered suitable
      for radical treatment, undergoing routine PET/CT staging comparing the results
      from CT and endoscopic ultrasound, as well as multi-disciplinary team records.
      Adenocarcinoma and squamous cell carcinoma were compared for maximum Standardised
      Uptake Value (SUV(max)), involvement of local lymph nodes and distant metastases.
      RESULTS: PET/CT provided additional information in 37 patients (18.5%) and
      directly altered management in 34 (17%): 22 (11%) were upstaged; 15 (7.5%) were
      downstaged, 12 of whom (6%) received radical treatment. There were 11 false
      negatives (5.5%) and 1 false positive (0.5%). SUV(max) was significantly lower
      for adenocarcinoma than squamous cell carcinoma (median 9.1 versus 13.5, p =
      0.003). CONCLUSIONS: Staging with PET/CT offers additional benefit over
      conventional imaging and should form part of routine staging for oesophageal
      cancer. Adenocarcinoma and squamous cell carcinoma display significantly
      different FDG-avidity.

PMID- 20821014
TI  - Fetal liver iron overload: the role of MR imaging.
AB  - OBJECTIVE: To assess the potential role of MR imaging in the diagnosis of fetal
      liver iron overload. METHODS: We reviewed seven cases of abnormal liver signal in
      fetuses referred to MR imaging in a context of suspected congenital infection (n
      = 2), digestive tract anomalies (n = 3) and hydrops fetalis (n = 2). The average
      GA of the fetuses was 31 weeks. The antenatal diagnoses were compared with
      histological data (n = 6) and postnatal work-up (n = 1). RESULTS: Magnetic
      resonance imaging demonstrated unexpected abnormal fetal liver signal suggestive
      of iron overload in all cases. The iron overload was confirmed on postnatal
      biopsy (n = 2) and fetopathology (n = 4). The final diagnosis was hepatic
      hemosiderosis (haemolytic anaemia (n = 2) and syndromal anomalies (n = 2)) and
      congenital haemochromatosis (n = 3). In all cases, the liver appeared normal on
      US. CONCLUSIONS: Magnetic resonance is the only imaging technique able to
      demonstrate liver iron overload in utero. Yet, the study outlines the fundamental
      role of MR imaging in cases of congenital haemochromatosis. The antenatal
      diagnosis of such a condition may prompt ante-(in the case of recurrence) or
      neonatal treatment, which might improve the prognosis.

PMID- 20821015
TI  - Functional effects of beta1-adrenoceptor polymorphisms on the hemodynamic
      response to dobutamine with and without beta-blocker administration.
AB  - BACKGROUND: The relevance of the Arg389Gly- and Ser49Gly-beta1-adrenoceptor (AR)
      polymorphisms for cardiovascular function and pharmacotherapy is controversial.
      METHODS: Out of 38 healthy male volunteers who were screened for both types of
      the beta1-AR polymorphism 23 subjects underwent dobutamine stress
      echocardiography at baseline, after administration of metoprolol succinate (n =
      18, 190 mg/day) and 44 h after abrupt termination of the beta-blocker (n = 17).
      Heart rate (HR), systolic blood pressure (SAP), HR-corrected left ventricular
      circumferential fiber shortening (VCF(C)), cardiac output (CO), systemic vascular
      resistance (SVR) and left ventricular end-systolic meridional wall stress (EsMWS)
      were measured. beta1-AR gene polymorphisms were analyzed by TaqMan-PCR. RESULTS:
      Genotype frequency distributions and allele frequencies of the Gly389Arg and
      Ser49Gly polymorphisms of the beta1-AR were similar to published data. Although
      body surface area was similar for Arg/Arg subjects and Gly carriers the latter
      group revealed smaller left ventricular end-diastolic (-0.4 cm, p = 0.04) and end
      systolic LV dimensions (-0.4 cm, p = 0.01). During dobutamine stimulation before,
      during and after termination of metoprolol coadministration no significant effect
      of the Arg389Gly-beta1-AR polymorphism on HR, SAP, CO and VCF(c) was detected. In
      contrast, SVR (p = 0.01) and EsMWS (p = 0.04) were significantly higher in
      Arg/Arg subjects. The VCF(C)-EsMWS regressions were similar for both groups, but
      revealed a minutely higher baseline contractility in the Arg/Arg group (p <
      0.01). The beta1-AR Ser49Gly polymorphism had no effect on any of the measured
      parameters. CONCLUSIONS: Although the Arg389Gly-beta1-AR polymorphism has only
      minor relevance for LV contractility it may impact left ventricular size and
      afterload. The Ser49Gly-beta1-AR polymorphism has no relevant effect on LV
      geometry or function.

PMID- 20821016
TI  - Ivabradine for the treatment of stable angina pectoris in octogenarians.
AB  - PURPOSE: In patients >80 years (octogenarians), there is an increased incidence
      of bradycardia due to age-related alteration of the sinus node, AV node, and the
      conduction system. Therefore, the treatment of angina pectoris with beta-blockers
      may be limited by bradycardia. The REDUCTION multicenter study evaluated the
      efficacy of ivabradine in stable angina pectoris in everyday practice. This
      subgroup analysis evaluated the efficacy and safety of ivabradine in
      octogenarians. METHODS: A total of 4,954 patients were included in the REDUCTION
      study for treatment of stable angina pectoris. This group included 382
      octogenarians (mean age 83 +/- 2.9 years) who were followed up over 4 months.
      Patients were treated with ivabradine in flexible doses (2.5, 5, or 7.5 mg bid).
      Heart rate (HR), angina pectoris attacks, nitrate consumption, overall efficacy,
      and tolerance were evaluated. RESULTS: After 4 months of treatment with
      ivabradine, HR was reduced by 12.0 +/- 12.0 bpm from 83.0 +/- 15.4 to 71.0 +/-
      10.1 bpm (p < 0.0001). Angina pectoris attacks were reduced from 3.0 +/- 4.6 to
      0.8 +/- 1.8 per week (p < 0.0001). Consumption of nitrates decreased from 4.2 +/-
      5.1 to 1.2 +/- 2.7 (p < 0.0001). Four patients reported suspected adverse drug
      reactions. In one patient a syncope occurred. There was no symptomatic
      bradycardia reported. Efficacy and tolerance were assessed as 'very good/good'
      for 95 and 99%. CONCLUSIONS: The results demonstrate that ivabradine efficiently
      reduces HR, number of angina attacks, and nitrate consumption in octogenarian
      patients. The treatment was safe and well tolerated without relevant bradycardia.

PMID- 20821017
TI  - Time between first symptoms and diagnosis in patients with acute pulmonary
      embolism: are patients with recurrent episodes diagnosed earlier?
AB  - BACKGROUND: Early diagnosis can be life-saving in acute pulmonary embolism (PE).
      It is unknown, whether patients with recurrent PE are diagnosed earlier than
      those with their first episode. METHODS: Admission data of patients with
      symptomatic acute PE were reviewed over a period of 47 months. Delay in
      diagnosis, demographics, body mass index, comorbidity, mortality, risk factors
      for venous thromboembolism and socio-economic status were recorded. RESULTS: 56
      out of 248 patients had recurrent PE, 192 patients were hospitalized because of
      their first episode. Delay in diagnosis after symptom onset was significantly
      greater in patients with recurrent than in patients with their first PE (3.4 +/-
      2.3 vs. 2.2 +/- 1.7 days, p = 0.006). Recurrent PE was significantly more often
      unprovoked (p < 0.001); by contrast, preceding trauma or surgery were
      significantly (p = 0.007) more frequent in first PE. CONCLUSIONS: Missing
      predisposing factors in unprovoked PE might explain the greater delay in
      diagnosis in recurrent PE. Physicians should focus more on informing patients
      about the possibility of PE recurrence and associated symptoms and thereby enable
      earlier diagnosis in recurrent PE.

PMID- 20821018
TI  - Transient elevation of NT-pro-BNP as a predictor for myocardial ischemia.

PMID- 20821019
TI  - Cardiac memory in humans: vectocardiographic quantification in cardiac
      resynchronization therapy.
AB  - BACKGROUND: "Cardiac memory" (CM) refers to a change in repolarization induced by
      an altered pathway of activation. The effects of biventricular pacing on CM
      induction have not been investigated. OBJECTIVE: To investigate the development
      of CM during cardiac resynchronization therapy (CRT) through vectorcardiography
      (VCG). METHODS: Eleven patients undergoing CRT were enrolled. VCG was acquired
      during spontaneous ventricular activation at baseline and during AAI and DDD
      pacing immediately after and 7, 14, 21 and 60 days after the implantation.
      RESULTS: At 1-week follow-up, during AAI pacing T vector angles significantly
      changed (azimuth 23 +/- 19 degrees ; p = 0.002; elevation 23 +/- 27 degrees ; p =
      0.019) and magnitude significantly increased (baseline 1.13 +/- 0.69 mV; 7 days:
      1.77 +/- 1.27 mV; p = 0.026). T angle changes remained stable throughout the
      follow-up period while a further significant increase in magnitude was observed
      at 60 days (2.21 +/- 1.50 mV; p = 0.01 vs. baseline and p = 0.04 vs. 7 days).
      Paced T vector magnitude at implant (2.24 +/- 1.25 mV) decreased significantly at
      7 days (1.64 +/- 1.26 mV; p = 0.030) with a further significant decrease at 60
      days (1.40 +/- 1.18 mV; p = 0.003 vs. baseline; p = 0.02 vs. 7 days). CONCLUSION:
      CRT induces a significant change in T vector magnitude, azimuth, and elevation
      after resumption of spontaneous ventricular activation after 7 days from
      implantation. While further changes in T vector angle were not observed, after 2
      months of CRT a significant decrease of paced T vector magnitude and a
      significant increase of spontaneous T vector magnitude were observed.

PMID- 20821020
TI  - Use of ivabradine in catecholamine-induced tachycardia after high-risk cardiac
      surgery.

PMID- 20821021
TI  - Ecstasy-induced myocardial infarction in a teenager: rare complication of a
      widely used illicit drug.

PMID- 20821022
TI  - Non-compaction cardiomyopathy of the left ventricle diagnosed by cardiac magnetic
      resonance in a 2-generation family.

PMID- 20821023
TI  - Headspace measurements of irradiated in vitro cultured cells using PTR-MS.
AB  - A pilot study was performed to evaluate a new concept for a radiation
      biodosimetry method. Proton transfer reaction-mass spectrometry (PTR-MS) was used
      to find out whether radiation induces changes in the composition of volatile
      organic compounds (VOCs) in the headspace of in vitro cultured cells. Two
      different cell lines, retinal pigment epithelium cells hTERT-RPE1 and lung
      epithelium cells A-549, were irradiated with gamma radiation at doses of 4 Gy and
      8 Gy. For measuring the cell-specific effects, the VOC concentrations in the
      headspace of flasks containing cells plus medium, as well as of flasks containing
      pure medium were analyzed for changes before and after irradiation. No
      significant radiation-induced alterations in VOC concentrations in the headspace
      could be observed after irradiation.

PMID- 20821024
TI  - Seasonal changes in haematology, lymphocyte transferrin receptors and
      intracellular iron in Ironman triathletes and untrained men.
AB  - We investigated whether 12 months of chronic endurance training would affect
      haematology, CD4(+) lymphocyte transferrin receptor (CD71) expression, CD4(+)
      intracellular iron and the incidence of upper respiratory tract illnesses (URTI)
      in Ironman triathletes compared with untrained men. Resting venous blood samples
      were taken from 15 Ironman triathletes (TR 30 +/- 5 year) and 12 untrained men
      (UT 30 +/- 6 year) every 4 weeks for 12 months. Erythrocyte, leukocyte and
      platelet concentration, haematocrit, haemoglobin (Hb) and mean corpuscular
      haemoglobin (MCHC) were measured with a full blood count. CD4(+) lymphocytes were
      analysed for changes in transferrin receptor (CD71) expression (CD4(+)CD71(+)),
      and intracellular iron (Fe(3+)), by flow cytometry. The TR group had
      significantly lower Hb, MCHC, and platelets for 10, 9 and 11 months,
      respectively; lower CD4(+)CD71(+) (3 months) and Fe(3+) (1 month), respectively;
      higher CD4(+)CD71(+) (1 month); a higher lymphocyte count for 4 months. There
      were no between-group differences in other variables. In both groups haematology
      and lymphocytes increased during spring, early summer and winter and decreased
      during late summer/late winter, with an inverse relationship between
      CD4(+)CD71(+) and Fe(3+). The TR group reported significantly fewer URTI than the
      UT. Low Hb and MCHC suggest an iron deficiency which may affect triathlete
      performance. Monthly changes in lymphocytes, CD4(+)CD71(+) and Fe(3+) suggested
      that spring, summer and late autumn are associated with CD4(+) proliferation.
      There may be seasonal relationships between haematology and lymphocyte function,
      independent of endurance training, possibly affecting performance but not the
      incidence of URTI.

PMID- 20821025
TI  - Higher resistance to herbivory in introduced compared to native populations of a
      seaweed.
AB  - Non-indigenous species (NIS) are important components of global change, and in
      order to manage such species it is important to understand which factors affect
      their success. Interactions with enemies in the new range have been shown to be
      important for the outcome of introductions, but thus far most studies on NIS
      enemy interactions have considered only specialist herbivores in terrestrial
      systems. Here we present the results from the first biogeographic study that
      compares herbivore resistance between populations in the native and new region of
      a non-indigenous seaweed. We show that low consumption of the non-indigenous
      seaweed by a generalist herbivore is caused by higher chemical defence levels and
      herbivore resistance in the new range-and not by the failure of the herbivore to
      recognise the non-indigenous seaweed as a suitable host. Since most seaweed
      herbivore interactions are dominated by generalist herbivores, this pattern could
      be common in marine communities. Our results also reveal that traits used to
      predict the invasive potential of species, such as their resistance to enemies,
      can change during the invasion process, but not always in the way predicted by
      dominant theories.

PMID- 20821026
TI  - Climate-based models for West Nile Culex mosquito vectors in the Northeastern US.
AB  - Climate-based models simulating Culex mosquito population abundance in the
      Northeastern US were developed. Two West Nile vector species, Culex pipiens and
      Culex restuans, were included in model simulations. The model was optimized by a
      parameter-space search within biological bounds. Mosquito population dynamics
      were driven by major environmental factors including temperature, rainfall,
      evaporation rate and photoperiod. The results show a strong correlation between
      the timing of early population increases (as early warning of West Nile virus
      risk) and decreases in late summer. Simulated abundance was highly correlated
      with actual mosquito capture in New Jersey light traps and validated with field
      data. This climate-based model simulates the population dynamics of both the
      adult and immature mosquito life stage of Culex arbovirus vectors in the
      Northeastern US. It is expected to have direct and practical application for
      mosquito control and West Nile prevention programs.

PMID- 20821027
TI  - Breakthrough in three-dimensional scoliosis diagnosis: significance of horizontal
      plane view and vertebra vectors.
AB  - Scoliosis is a multifactorial three-dimensional (3D) spinal deformity with
      integral and directly related vertebral deviations in the coronal, sagittal and
      horizontal planes. Current classification and diagnostic methods rely on two
      dimensional (2D) frontal and lateral X-ray images; no routine methods are
      available for the visualization and quantitative evaluation of deviations in the
      horizontal plane. The EOS 2D/3D system presented here is a new, low-dose,
      orthopedic radiodiagnostic device based on Nobel prize-winning X-ray detection
      technology with special software for 3D surface reconstruction capabilities that
      finally led to a breakthrough in scoliosis diagnosis with high-quality, realistic
      3D visualization and accurate quantitative parametric analysis. A new concept
      introducing vertebra vectors and vertebra vector parametric calculations is
      introduced that furnishes simplified visual and intelligible mathematical
      information facilitating interpretation of EOS 2D/3D data, especially with regard
      to the horizontal plane top view images. The concept is demonstrated by a
      reported scoliotic case that was readily characterized through information
      derived from vertebra vectors alone, supplemented with the current angulation
      measurement methods in the coronal and sagittal planes and axial vertebral
      rotation measurements in the horizontal plane, with a calibrated 3D coordinate
      system suitable for inter-individual comparisons. The new concept of vertebra
      vectors may serve as a basis for a truly 3D classification of scoliosis.

PMID- 20821028
TI  - Placement of pedicle screws using three-dimensional fluoroscopy-based navigation
      in lumbar vertebrae with axial rotation.
AB  - Despite potential advantages of three-dimensional fluoroscopy-based navigation,
      there still remain a lot of controversies about the indications of this
      technology, especially whether it is worthy of being used in placement of pedicle
      screws in lumbar spine. However, according to the inconsistent conclusions
      reported in the literature and our experiences, the traditional method relying on
      anatomical landmarks and fluoroscopic views to guide lumbar pedicle screw
      insertion is unable to meet the requirement of precise screw placement. Based on
      our observation, screw malposition seems to occur concomitant with vertebral
      axial rotation which is a ubiquitous phenomenon. Three-dimensional fluoroscopy
      based navigation can provide the most valuable axial images in real-time, so it
      may be useful for placement of pedicle screws in lumbar spine. This study was
      intended to evaluate the effect of axial rotation of lumbar vertebrae on the
      accuracy of pedicle screw placement using the traditional method, as well as
      assess the value of three-dimensional fluoroscopy-based navigation in improving
      the accuracy. Sixteen lumbar simulation models at different degrees of axial
      rotation (0 degrees , 5 degrees , 10 degrees , and 20 degrees ), with every four
      assigned the same degree, were equally divided into two groups (traditional
      method group and three-dimensional fluoroscopy-based navigation group). Random
      placement of pedicle screws was carried out, followed by CT scan postoperatively.
      Then the outer pedicle cortex contours were depicted from reconstructed sectional
      pedicle images using Photoshop. The accuracy of pedicle screw placement was
      evaluated by determining the interrelationship between screw trajectory and
      pedicle cortex (quality), and measuring the shortest distance from pedicle screw
      axis to outer cortex of the pedicle (quantity). Eighty pedicle screws were
      implanted, respectively, in each group. In traditional method group, statistical
      difference existed in the accuracy of pedicle screw placement at different axial
      rotational degrees (P < 0.05). With degrees increasing, the accuracy declined.
      The accuracy of three-dimensional fluoroscopy-based navigation group was higher
      than traditional method group in vertebrae with axial rotation (P < 0.01). In
      qualitative evaluation, the accuracy of the two methods had statistical
      difference when the degree was 20 degrees , and in quantitative evaluation,
      statistical difference existed in 5 degrees , 10 degrees , and 20 degrees  of
      vertebral axial rotation.

PMID- 20821030
TI  - Grynfelt hernia: case report and literature review.
AB  - Back lumbar hernia is a rare abdominal wall defect that usually presents
      spontaneously after trauma or lumbar surgery or, less frequently, during infancy
      (congenital). Few reports have been published in the literature describing
      primary lumbar hernia. A general surgeon will have the opportunity to repair only
      one or a few lumbar hernia cases in his/her lifetime. We report a case of a
      healthy 50-year-old man, with no previous surgeries or history of trauma, who
      presented to the outpatient department with abdominal discomfort, pain, and a
      sensation of a growing mass on his lower left back for 4 years. CT scan of the
      abdomen showed a mass in the left posterolateral abdominal wall. Specifically, a
      herniation of retroperitoneal fat between the erector spinae muscle group and
      internal oblique muscles through aponeurosis of the transversalis muscle
      (Grynfeltt hernia). The patient underwent a small lumbotomy, polypropylene mesh
      was placed and he recovered well. Although many techniques have been described
      for the surgical management of such hernias, none of them can be recommended as
      the preferred method. Our impression, however, is that the open approach, with a
      small lumbotomy, seems to be easy, safe and presents good postoperative recovery.

PMID- 20821031
TI  - The wheat (T. aestivum) sucrose synthase 2 gene (TaSus2) active in endosperm
      development is associated with yield traits.
AB  - Sucrose synthase catalyzes the reaction sucrose + UDP -> UDP-glucose + fructose,
      the first step in the conversion of sucrose to starch in endosperm. Previous
      studies identified two tissue-specific, yet functionally redundant, sucrose
      synthase (SUS) genes, Sus1 and Sus2. In the present study, the wheat Sus2
      orthologous gene (TaSus2) series was isolated and mapped on chromosomes 2A, 2B,
      and 2D. Based on sequencing in 61 wheat accessions, three single-nucleotide
      polymorphisms (SNPs) were detected in TaSus2-2B. These formed two haplotypes (Hap
      H and Hap-L), but no diversity was found in either TaSus2-2A or TaSus2-2D. Based
      on the sequences of the two haplotypes, we developed a co-dominant marker, TaSus2
      2B ( tgw ), which amplified 423 or 381-bp fragments in different wheat
      accessions. TaSus2-2B ( tgw ) was located between markers Xbarc102.2 and Xbarc91
      on chromosome 2BS in a RIL population from Xiaoyan 54 * Jing 411. Association
      analysis suggested that the two haplotypes were significantly associated with
      1,000 grain weight (TGW) in 89 modern wheat varieties in the Chinese mini-core
      collection. Mean TGW difference between the two haplotypes over three cropping
      seasons was 4.26 g (varying from 3.71 to 4.94 g). Comparative genomics analysis
      detected major kernel weight QTLs not only in the chromosome region containing
      TaSus2-2B (tgw), but also in the collinear regions of TaSus2 on rice chromosome 7
      and maize chromosome 9. The preferred Hap-H haplotype for high TGW underwent very
      strong positive selection in Chinese wheat breeding, but not in Europe. The
      geographic distribution of Hap-H was perhaps determined by both latitude and the
      intensity of selection in wheat breeding.

PMID- 20821033
TI  - The vestibular system mediates sensation of low-frequency sounds in mice.
AB  - The mammalian inner ear contains sense organs responsible for detecting sound,
      gravity and linear acceleration, and angular acceleration. Of these organs, the
      cochlea is involved in hearing, while the sacculus and utriculus serve to detect
      linear acceleration. Recent evidence from birds and mammals, including humans,
      has shown that the sacculus, a hearing organ in many lower vertebrates, has
      retained some of its ancestral acoustic sensitivity. Here we provide not only
      more evidence for the retained acoustic sensitivity of the sacculus, but we also
      found that acoustic stimulation of the sacculus has behavioral significance in
      mammals. We show that the amplitude of an elicited auditory startle response is
      greater when the startle stimuli are presented simultaneously with a low
      frequency masker, including masker tones that are outside the sensitivity range
      of the cochlea. Masker-enhanced auditory startle responses were also observed in
      otoconia-absent Nox3 mice, which lack otoconia but have no obvious cochlea
      pathology. However, masker enhancement was not observed in otoconia-absent Nox3
      mice if the low-frequency masker tones were outside the sensitivity range of the
      cochlea. This last observation confirms that otoconial organs, most likely the
      sacculus, contribute to behavioral responses to low-frequency sounds in mice.

PMID- 20821035
TI  - Ethnic differences in health and use of health care: the questions to be
      answered.

PMID- 20821032
TI  - The effect of cochlear-implant-mediated electrical stimulation on spiral ganglion
      cells in congenitally deaf white cats.
AB  - It has long been observed that loss of auditory receptor cells is associated with
      the progressive degeneration of spiral ganglion cells. Chronic electrical
      stimulation via cochlear implantation has been used in an attempt to slow the
      rate of degeneration in cats neonatally deafened by ototoxic agents but with
      mixed results. The present study examined this issue using white cats with a
      history of hereditary deafness as an alternative animal model. Nineteen cats
      provided new data for this study: four normal-hearing cats, seven congenitally
      deaf white cats, and eight congenitally deaf white cats with unilateral cochlear
      implants. Data from additional cats were collected from the literature.
      Electrical stimulation began at 3 to 4 or 6 to 7 months after birth, and cats
      received stimulation for approximately 7 h a day, 5 days a week for 12 weeks.
      Quantitative analysis of spiral ganglion cell counts, cell density, and cell body
      size showed no marked improvement between cochlear-implanted and congenitally
      deaf subjects. Average ganglion cell size from cochlear-implanted and
      congenitally deaf cats was statistically similar and smaller than that of normal
      hearing cats. Cell density from cats with cochlear implants tended to decrease
      within the upper basal and middle cochlear turns in comparison to congenitally
      deaf cats but remained at congenitally deaf levels within the lower basal and
      apical cochlear turns. These results provide no evidence that chronic electrical
      stimulation enhances spiral ganglion cell survival, cell density, or cell size
      compared to that of unstimulated congenitally deaf cats. Regardless of ganglion
      neuron status, there is unambiguous restoration of auditory nerve synapses in the
      cochlear nucleus of these cats implanted at the earlier age.

PMID- 20821036
TI  - Multifocal visual evoked potential recordings in compressive optic neuropathy
      secondary to pituitary adenoma.
AB  - To investigate the effect of pituitary adenoma compressing the optic chiasm on
      multifocal visual evoked potential (mfVEP) responses and to compare these
      responses with visual field defects seen on static automated perimetry (SAP).
      Eight eyes of four subjects (median age, 41.50 years; interquartile range, 33-51
      years) who were diagnosed with pituitary adenoma on magnetic resonance imaging
      (MRI) and seen to have a bitemporal visual field defect on standard automated
      perimetry (SAP), and twelve age-matched normal subjects (median age, 47.00 years;
      interquartile range, 34.75-51.75 years) were subjected to multifocal visual
      evoked potential (mfVEP) testing. The monocular latencies and monocular
      amplitudes of each sector of cases were compared with the responses of normative
      database. The topography of the mfVEP response was compared with corresponding
      field defect as seen in total deviation threshold on SAP to allow a comparison
      with conventional subjective perimetry. The mfVEP amplitudes were reduced in the
      areas with visual field defect on SAP. In 6 out of 8 eyes, locations with
      preserved amplitudes and no visual defects showed prolonged latency. A prolonged
      median latency of 9.17 ms (interquartile range, 3.44-17.69 ms) in cases was seen
      when compared to the median latency of 1.67 ms (interquartile range, 0.94-4.17
      ms) in age-matched controls with P value of 0.054. Chiasmal compression due to
      pituitary adenoma causes the reduction of amplitudes and prolongation of
      latencies of the mfVEP response. The mfVEP can be used to assess objectively the
      topography of the visual field in compressive optic neuropathy secondary to
      pituitary adenomas. It can be used in assessing the subjects whose visual field
      report is unreliable and prolonged median latency can be an early sign of the
      disease.

PMID- 20821037
TI  - Equation or algorithm: differences and choosing between them.
AB  - The issue of whether formal reasoning or a computing-intensive approach is the
      most efficient manner to address scientific questions is the subject of some
      considerable debate and pertains not only to the nature of the phenomena and
      processes investigated by scientists, but also the nature of the equation and
      algorithm objects they use. Although algorithms and equations both rely on a
      common background of mathematical language and logic, they nevertheless possess
      some critical differences. They do not refer to the same level of symbolization,
      as equations are based on integrated concepts in a denotational manner, while
      algorithms specifically break down a complex problem into more elementary
      operations, in an operational manner. They may therefore be considered as suited
      to the representation of different phenomena. Specifically, algorithms are by
      nature sufficient to represent weak emergent phenomena, but not strong emergent
      patterns, while equations can do both. Finally, the choice between equations and
      algorithms are by nature sufficient to represent weak emergent phenomena, but not
      strong emergent patterns, while equations behave conversely. We propose a
      simplified classification of scientific issues for which both equation- and/or
      algorithm-based approaches can be envisaged, and discuss their respective pros
      and cons. We further discuss the complementary and sometimes conflicting uses of
      equations and algorithms in a context of ecological theory of metapopulation
      dynamics. We finally propose both conceptual and practical guidelines for
      choosing between the alternative approaches.

PMID- 20821038
TI  - Attributable risk in men in two French case-control studies on mesothelioma and
      asbestos.
AB  - Pleural mesothelioma is a primary tumor of the pleura that is mainly due to
      asbestos exposure. To study the relationship between mesothelioma and
      occupational asbestos exposure in France, two case-control studies (A and B) were
      conducted. A substantial difference in the attributable risk in the population
      (AR(p)) was observed among men: 44.5% (95% CI: [32.6-56.4]) in study A and 83.2%
      (95% CI: [76.8-89.6]) in study B. As different exposure assessment expert methods
      were used, the main objective of this work was to re-estimate the AR(p) men in
      two case-control studies according to a common standardized exposure assessment
      by using a Job Exposure Matrix (JEM) and to assess the role of subjects'
      selection. The initial observed AR(p) difference was maintained: 36.3% (95% CI:
      [24.3-50.3]) in study A and 69.7% (95% CI: [51.7-83.2]) in study B. Further
      investigations highlighted the potential selection bias introduced in both
      studies, especially among controls. The AR(p) could be underestimated in study A
      and overestimated in study B. After weighting subjects according to distribution
      of socio-economic status in the general population for controls and according to
      distribution of socio-economic status of cases registered by the French National
      Mesothelioma Surveillance Program, re-estimated AR(p) values were 52.4% in study
      A and 70.2% in study B. These results provide additional information to describe
      the relationship between pleural mesothelioma and occupational asbestos exposure,
      but also confirm the importance of subjects' recruitment in case control studies,
      particularly control selection.

PMID- 20821039
TI  - Risk factors for otitis media in children with special emphasis on the role of
      colonization with bacterial airway pathogens: the Generation R study.
AB  - Acute otitis media is the most frequent diagnosis in children visiting
      physicians' offices. Risk factors for otitis media have been widely studied. Yet,
      the correlation between bacterial carriage and the development of otitis media is
      not entirely clear. Our aim was to study in a population-based prospective cohort
      the risk factors for otitis media in the second year of life with special
      emphasis on the role of colonization with Streptococcus pneumoniae, Haemophilus
      influenzae and Moraxella catarrhalis. The study was embedded in the Generation R
      Study. Data on risk factors and doctor-diagnosed otitis media were obtained by
      midwives, hospital registries and postal questionnaires in the whole cohort (n =
      7,295). Nasopharyngeal swabs were obtained at the age of 1.5, 6 and 14 months in
      the focus cohort (n = 1,079). Of these children, 2,515 (47.2%) suffered at least
      one period of otitis media in their second year of life. The occurrence of otitis
      media during the follow-up period in the first 6 months of life and between 6 and
      12 months of age was associated with the risk of otitis media in the second year
      of life (aOR, 1.83 95% CI 1.24-2.71 and aOR 2.72, 95% CI 2.18-3.38,
      respectively). Having siblings was associated with an increased risk for otitis
      media in the second year of life (aOR 1.42, 95% CI 1.13-1.79). No associations
      were found between bacterial carriage in the first year of life and otitis media
      in the second year of life. In our study, otitis media in the first year of life
      is an independent risk factor for otitis media in the second year of life.
      Surprisingly, bacterial carriage in the first year of life did not add to this
      risk. Moreover, no association was observed between bacterial carriage in the
      first year of life and otitis in the second year of life.

PMID- 20821041
TI  - TLR1/2, TLR7, and TLR9 signals directly activate human peripheral blood naive and
      memory B cell subsets to produce cytokines, chemokines, and hematopoietic growth
      factors.
AB  - Recently, it has been reported that using multiple signals, murine and human B
      cells secrete several cytokines with pro-inflammatory and immunoregulatory
      properties. We present the first comprehensive analysis of 24 cytokines,
      chemokines, and hematopoietic growth factors production by purified human
      peripheral blood B cells (CD19+), and naive (CD19+CD27-) and memory (CD19+CD27+)
      B cells in response to direct and exclusive signaling provided by toll-like
      receptor (TLR) ligands Pam3CSK (TLR1/TLR2), Imiquimod (TLR7), and GpG-ODN2006
      (TLR9). All three TLR ligands stimulated B cells (CD19+) to produce cytokines IL
      1alpha, IL-1beta, IL-6, TNF-alpha, IL-13, and IL-10, and chemokines MIP-1alpha,
      MIP-1beta, MCP-1, IP-10, and IL-8. However, GM-CSF and G-CSF production was
      predominantly induced by TLR2 agonist. Most cytokines/chemokines/hematopoietic
      growth factors were predominantly or exclusively produced by memory B cells, and
      in general, TLR2 signal was more powerful than signal provided viaTLR7 and TLR9.
      No significant secretion of eotaxin, IFN-alpha, IFN-gamma, IL-2, IL-3, IL-4, IL
      5, IL-7, IL-15, IL-17, IL-12p40, IL-12p70, and TNF-beta (lymphotoxin) was
      observed. These data demonstrate that human B cells can be directly activated
      viaTLR1/TLR2, TLR7, and TLR9 to induce secretion of cytokines, chemokines, and
      hematopoietic growth factors and suggest a role of B cells in immune response
      against microbial pathogenesis and immune homeostasis.

PMID- 20821040
TI  - Cancer immunotherapy and nanomedicine.
AB  - The immune system has the ability to recognize and kill pre-cancer and cancer
      cells. However, with the immune system's surveillance, the survival tumor cells
      learn how to escape the immune system after immunoselection. Cancer immunotherapy
      develops strategies to overcome these problems. Nanomedicine applications in
      cancer immunotherapy include the nanodiagnostics and nanobiopharmaceuticals. In
      cancer nanodiagnostics, it looks for specific "molecular signatures" in cancer
      cells or their microenvironment by using genomics and proteomics.
      Nanobiopharmaceuticals is the field that studies nanotechnology-based therapeutic
      agents and drug carriers. DNA, RNA, peptides, proteins and small molecules can
      all be used as cancer therapies when formulated in nanocarriers. Currently,
      cancer vaccines are applied in treatments with existing cancer or to prevent the
      development of cancer in certain high risk individuals. Most of the non-specific
      immune activation agents include adjuvants which enhance immunogenicity and
      accelerate and prolong the response of cancer vaccines. The carriers of vaccines,
      such as viruses and nanoparticles, have also been in clinical studies for many
      years. This review will discuss the relationships between the tumor and the
      immune system, and also will include topics covering the strategies used in
      eliminating tumors by using nanomedicine.

PMID- 20821043
TI  - Prolonged gonadotropin stimulation is associated with decreased ART success.
AB  - PURPOSE: to evaluate whether the duration of gonadotropin stimulation predicts
      the likelihood of live birth after ART. METHODS: all IVF or ICSI cycles using
      fresh autologous oocytes at our institution between January 2004 and December
      2007 were analyzed. RESULTS: out of 699 cycles resulting in oocyte retrieval, 193
      produced a live birth (27.6%). Women who achieved a live birth had a
      significantly shorter stimulation phase (11.1 vs. 11.5 days, respectively).
      Multivariable analysis suggested that 13 days or longer of stimulation decreased
      the likelihood of a live birth by 53% as compared to cycles that were 10-12 days
      long (odds ratio [OR] 0.47; 95% confidence interval [CI]: 0.30-0.75) after
      adjustment for female age, maximum historical FSH, total dose of gonadotropin
      received, oocytes retrieved, embryos transferred, antagonist suppression and PCOS
      diagnosis. CONCLUSIONS: prolonged duration of gonadotropin stimulation is an
      independent negative predictor of ART success in our cohort.

PMID- 20821042
TI  - Predictors of breastfeeding in overweight and obese women: data from Active
      Mothers Postpartum (AMP).
AB  - Excess maternal weight has been negatively associated with breastfeeding. We
      examined correlates of breastfeeding initiation and intensity in a racially
      diverse sample of overweight and obese women. This paper presents a secondary
      analysis of data from 450 women enrolled in a postpartum weight loss intervention
      (Active Mothers Postpartum [AMP]). Sociodemographic measures and body mass index
      (BMI), collected at 6 weeks postpartum, were examined for associations with
      breastfeeding initiation and lactation score (a measure combining duration and
      exclusivity of breastfeeding until 12 months postpartum). Data were collected
      September 2004-April 2007. In multivariable analyses, BMI was negatively
      associated with both initiation of breastfeeding (OR: .96; CI: .92-.99) and
      lactation score (beta -0.22; P = 0.01). Education and infant gestational age were
      additional correlates of initiation, while race, working full-time, smoking,
      parity, and gestational age were additional correlates of lactation score. Some
      racial differences in these correlates were noted, but were not statistically
      significant. Belief that breastfeeding could aid postpartum weight loss was
      initially high, but unrelated to breastfeeding initiation or intensity.
      Maintenance of this belief over time, however, was associated with lower
      lactation scores. BMI was negatively correlated with breastfeeding initiation and
      intensity. Among overweight and obese women, unrealistic expectations regarding
      the effect of breastfeeding on weight loss may negatively impact breastfeeding
      duration. In general, overweight and obese women may need additional
      encouragement to initiate breastfeeding and to continue breastfeeding during the
      infant's first year.

PMID- 20821044
TI  - Spindle and chromosome configurations of in vitro-matured oocytes from polycystic
      ovary syndrome and ovulatory infertile women: a pilot study.
AB  - PURPOSE: To evaluate the meiotic spindle and chromosomal distribution of in vitro
      matured oocytes from infertile nonobese women with PCOS and male or tubal causes
      of infertility (controls), and to compare in vitro maturation (IVM) rates between
      groups. METHODS: Seventy four patients (26 with PCOS and 48 controls) undergoing
      stimulated cycles of oocyte retrieval for ICSI were selected prospectively.
      Thirteen PCOS patients and 27 controls had immature oocytes retrieved submitted
      to IVM. After IVM, oocytes showing extrusion of the first polar body were fixed
      and processed for evaluation of the meiotic spindle and chromosome distribution
      by immunofluorescence microscopy. RESULTS: There were no differences between PCOS
      and control groups with respect to IVM rates (50.0% and 42.9%, respectively) nor
      the percentage of meiotic abnormalities in metaphase II oocytes (35.3% and 25%,
      respectively). CONCLUSIONS: In vitro-matured oocytes obtained from stimulated
      cycles of nonobese PCOS did not have an increased ratio of meiotic abnormalities.

PMID- 20821046
TI  - The TGF-beta/Smad pathway induces breast cancer cell invasion through the up
      regulation of matrix metalloproteinase 2 and 9 in a spheroid invasion model
      system.
AB  - Transforming growth factor-beta (TGF-beta) has opposing roles in breast cancer
      progression by acting as a tumor suppressor in the initial phase, but stimulating
      invasion and metastasis at later stages. In contrast to the mechanisms by which
      TGF-beta induces growth arrest, the pathways that mediate tumor invasion are not
      well understood. Here, we describe a TGF-beta-dependent invasion assay system
      consisting of spheroids of MCF10A1 normal breast epithelial cells (M1) and RAS
      transformed (pre-)malignant derivatives (M2 and M4) embedded in collagen gels.
      Both basal and TGF-beta-induced invasion of these cell lines was found to
      correlate with their tumorigenic potential; M4 showing the most aggressive
      behavior and M1 showing the least. Basal invasion was strongly inhibited by the
      TGF-beta receptor kinase inhibitor SB-431542, indicating the involvement of
      autocrine TGF-beta or TGF-beta-like activity. TGF-beta-induced invasion in
      premalignant M2 and highly malignant M4 cells was also inhibited upon specific
      knockdown of Smad3 or Smad4. Interestingly, both a broad spectrum matrix
      metalloproteinase (MMP) inhibitor and a selective MMP2 and MMP9 inhibitor
      mitigated TGF-beta-induced invasion of M4 cells, while leaving basal invasion
      intact. In line with this, TGF-beta was found to strongly induce MMP2 and MMP9
      expression in a Smad3- and Smad4-dependent manner. This collagen-embedded
      spheroid system therefore offers a valuable screening model for TGF-beta/Smad-
      and MMP2- and MMP9-dependent breast cancer invasion.

PMID- 20821045
TI  - The role of the Hoxa10/HOXA10 gene in the etiology of endometriosis and its
      related infertility: a review.
AB  - PURPOSE: endometriosis and its associated infertility have been the object of
      continuous research for over a century. To understand the molecular mechanisms
      underlying the disease, it has become necessary to determine the aspects of its
      etiology that are not explained by the retrograde menstruation theory. This could
      in turn elucidate how various clinical and surgical treatments might affect the
      evolution and remission of the disease. METHODS: this review is focused on the
      most recent clinical and laboratory findings regarding the association of HOXA10
      with endometriosis and infertility. RESULT: the homebox (Hox/HOX) proteins are
      highly conserved transcription factors that determine segmental body identities
      in multiple species, including humans. Hoxa10/HOXA10 is directly involved in the
      embryogenesis of the uterus and embryo implantation via regulation of downstream
      genes. Cyclical endometrial expression of Hoxa10/HOXA10, with a peak of
      expression occurring during the window of implantation, is observed in the adult
      in response to estrogen and progesterone. Women with endometriosis do not
      demonstrate the expected mid-luteal rise of HOXA10 expression, which might
      partially explain the infertility observed in many of these patients. Recent
      studies also demonstrated HOXA10 expression in endometriotic foci outside the
      Mullerian tract. CONCLUSIONS: multiple lines of evidence suggest that the actions
      of the homeobox A10 (Hoxa10/HOXA10) gene could account for some aspects of
      endometriosis.

PMID- 20821047
TI  - Anastrozole and letrozole: an investigation and comparison of quality of life and
      tolerability.
AB  - Previous studies have demonstrated that both anastrozole and letrozole are well
      tolerated. Letrozole suppresses estrogen to a greater degree than anastrozole in
      the serum and breast tumor. Concerns have been raised that greater potency may
      adversely affect patients' quality of life (QOL). One hundred eighty-one
      postmenopausal women with invasive estrogen receptor-positive breast cancers were
      randomized to receive either 12 weeks of letrozole followed by 12 weeks of
      anastrozole or the reverse sequence. One hundred and six received immediate
      adjuvant aromatase inhibitors (AIs) following surgery, and 75 received extended
      adjuvant therapy. The Functional Assessment of Cancer Therapy Endocrine Subscale
      (FACT-B-ES) QOL questionnaires were completed to assess QOL on each drug.
      Additional side-effect profiles were collected. Each patient completed a patient
      preference form. Twenty-one patients withdrew before study end, 10/179 (5.6%)
      while taking letrozole and 4/173 (2.3%) while taking anastrozole (P = 0.12).
      Tamoxifen-naive patients had a higher mean ES (endocrine symptoms subscale) score
      at entry versus those having extended therapy (66.0 vs. 61.9; P = 0.001). There
      was no significant change in FACT-B-ES (overall) scores or ES scores while
      patients were taking anastrozole or letrozole and no significant differences
      between drugs. Nearly 80% of patients reported one or more side effects with
      either agent. No differences in frequency, grade, or range of side effects were
      seen between drugs. Of 160 patients, 49 (30.6%) preferred letrozole, 57 (35.6%)
      preferred anastrozole, and 54 (33.8%) had no preference (P = 0.26, Pearson's Chi
      squared test). In conclusion, both AIs are equally well tolerated. There were no
      significant differences in QOL scores between the two drugs.

PMID- 20821048
TI  - Physiological and behavioural effects of imidacloprid on two ecologically
      relevant earthworm species (Lumbricus terrestris and Aporrectodea caliginosa).
AB  - Earthworms play key roles in soils and sub-lethal effects of environmental
      toxicants on these organisms should be taken seriously, since they might have
      detrimental effects on higher ecological levels. In laboratory experiments we
      have assessed sub-lethal effects (body mass change and cast production) of
      imidacloprid on two earthworm species commonly found in different agricultural
      soils (Lumbricus terrestris and Aporrectodea caliginosa). After 7 days of
      exposure in contaminated soil, a significant loss of body mass was found in both
      species exposed to imidacloprid concentrations as low as 0.66 mg kg(-1) dry soil.
      These losses ranged from 18.3 to 39% for A. caliginosa and from 7.4 to 32.4% for
      L. terrestris, respectively. Changes in cast production, a new biomarker
      previously validated using L. terrestris, was assessed by soil sieving using the
      recommended mesh size (5.6 mm) for L. terrestris and three different mesh sizes
      for A. caliginosa (5.6, 4 and 3.15 mm). The 4 mm mesh size proved to be the most
      suitable sieve size for A. caliginosa. Cast production increased by 26.2% in A.
      caliginosa and by 28.1% in L. terrestris at the lowest imidacloprid concentration
      tested (0.2 mg kg(-1) dry soil), but significantly decreased at higher
      concentrations (equal to and above 0.66 mg kg(-1) dry soil) in both earthworm
      species after the 7 days exposure experiment. These decreases in cast production
      ranged from 44.5 to 96.9% in A. caliginosa and from 42.4 to 95.7% in L.
      terrestris. The EC(50) for cast production were 0.84 (L. terrestris) and 0.76 mg
      kg(-1) dry soil (A. caliginosa), respectively. The detected sub-lethal effects
      were found close to the predicted environmental concentration (PEC) of
      imidacloprid, which is in the range of 0.33-0.66 mg kg(-1) dry soil. The
      biomarkers used in the present study, body mass change and changes in cast
      production, may be of ecological relevance and have shown high sensitivity for
      imidacloprid exposure of earthworms. The measurement of changes in cast
      production should be considered for inclusion in current standard tests.

PMID- 20821050
TI  - Characteristics of staff victims of psychiatric patient assaults: 20-year
      analysis of the Assaulted Staff Action Program.
AB  - Psychiatric patient assaults on healthcare staff are a worldwide occupational
      hazard. This present 20-year, retrospective study examined the characteristics of
      these staff victims in one public-sector, health care system and assessed the
      psychological support provided to these victims by the post-incident Assaulted
      Staff Action Program (ASAP). An additional analysis compared the victim
      characteristics in this same health care system at 10-, 15-, and 20-year
      intervals. The findings were consistent with earlier, worldwide studies. Staff
      victims tend to be younger, less formally educated, less experienced, and less
      trained mental health workers, residential house counselors, and trainees of
      differing disciplines. ASAP provided needed support to staff victims. Risk
      management strategies for safety, methodological issues, and the problem of
      denial in fielding a post-incident crisis intervention program for staff victims
      were discussed.

PMID- 20821049
TI  - Lethal and sublethal effects of cypermethrin to Hypsiboas pulchellus tadpoles.
AB  - The study of the effects of the insecticide cypermethrin (CY) technical grade and
      its Sherpa(r) commercial formulation on Hypsiboas pulchellus tadpoles assessing
      lethality, behavior, growth, and abnormalities under standardized laboratory
      conditions is reported. Observed behaviors were identified and categorized by
      means of a ranking system according to the loss of mobility. Results of acute
      lethal effects indicate higher potency for Sherpa(r) at this level of assessment.
      All effects on behavior showed an increasing degree of injury as insecticide
      concentration increased. Organisms exposed to technical grade CY showed lower
      body length with respect to controls from 3.44 ug CY/L to higher concentrations,
      whereas those exposed to Sherpa(r) exhibited lower growth from 0.83 ug CY/L. Both
      forms of the tested insecticide caused abnormalities between 0.34 and 4.18 ug
      CY/L, but 100% of malformed individuals was detected from 34.4 ug CY/L for those
      exposed to the technical grade CY, and from 8.36 ug CY/L for those exposed to
      Sherpa(r). This study proposes the use of easily identifiable and distinguishable
      sublethal end-points. The high input loads of CY in natural environments, the
      detected concentrations in the field, in addition to the low levels of this
      insecticide required to induce sublethal effects (which could eventually lead to
      death), allow for the conclusion that the insecticide is a risk factor for
      amphibians inhabiting agroecosystems.

PMID- 20821051
TI  - Substrate reduction therapy with miglustat in chronic GM2 gangliosidosis type
      Sandhoff: results of a 3-year follow-up.
AB  - GM2 gangliosidosis type Sandhoff is caused by a defect of beta-hexosaminidase, an
      enzyme involved in the catabolism of gangliosides. It has been proposed that
      substrate reduction therapy using N-butyl-deoxynojirimycin (miglustat) may delay
      neurological progression, at least in late-onset forms of GM2 gangliosidosis. We
      report the results of a 3-year treatment with miglustat (100 mg t.i.d) in a
      patient with chronic Sandhoff disease manifesting with an atypical, spinal
      muscular atrophy phenotype. The follow-up included serial neurological
      examinations, blood tests, abdominal ultrasound, and neurophysiologic, cognitive,
      brain, and muscle MRI studies. We document some minor effects on neurological
      progression in chronic Sandhoff disease by miglustat treatment, confirming the
      necessity of phase II therapeutic trials including early-stage patients in order
      to assess its putative efficacy in chronic Sandhoff disease.

PMID- 20821052
TI  - An adult onset case of alpha-methyl-acyl-CoA racemase deficiency.
AB  - alpha-Methyl-acyl-CoA-racemase (AMACR) deficiency (OMIM 604489) is a rare
      peroxisomal disorder with a variable age of onset from infancy to late adulthood.
      We describe a 45-year-old male with a history of seizures who presented with
      relapsing encephalopathy. Laboratory studies revealed an elevated serum pristanic
      acid concentration, an elevated pristanic/phytanic acid ratio, as well as the
      previously described homozygous mutation in the AMACR gene, c.154T>C, consistent
      with AMACR deficiency. This homozygous mutation is associated with a variable
      phenotype ranging from neonatal cholestasis to late-onset sensorimotor
      neuropathy. Dietary pristanic acid restriction was attempted to improve clinical
      status and the patient has remained in remission for more than 16 months.

PMID- 20821053
TI  - Antenatal diagnosis of pompe disease by fetal echocardiography: impact on outcome
      after early initiation of enzyme replacement therapy.
AB  - Hypertrophic cardiomyopathy (HCM) affects most infants with Pompe disease (PD),
      and may serve as a marker for its antenatal diagnosis (ANDx) by fetal
      echocardiography (FE). Fetuses diagnosed with HCM between 2006 and 2009 were
      included in this study. HCM, defined as Z-score of mean left ventricular wall
      thickness (LVWT) and/or mass (LVM) above 2, was detected in 5/1,268 fetuses
      (0.39%) carried by 1,137 pregnant women referred for FE. Three fetuses (0.24%)
      had postnatal confirmation of PD. Their gestational age and fetal weight at
      diagnosis was (mean +/- standard deviation) 31 +/- 3.6 weeks and 1.9 +/- 0.2 kg,
      respectively. Fetal Z-score of LVM and LVWT was 3.8 +/- 0.9 and 3.1 +/- 0.6,
      respectively. Postnatally, acid alpha-glucosidase (GAA) enzyme activity was
      nearly absent in all patients, 2 were homozygous for the mutation 1327-2A>G in
      the GAA gene, and 1 was homozygous for 340insT. Enzyme replacement therapy (ERT)
      was initiated 4.9 +/- 7.8 days after birth (range 2 h-14 days), and continued
      every 2 weeks. Two infants are alive at 4 and 31 months, and one died of
      aspiration pneumonia at 19 months. Cardiac hypertrophy resolved after 10-12 weeks
      of ERT in all patients, and none required any respiratory support. One patient
      had normal neurodevelopmental assessment at 25 months, and one had severe global
      delay at 15 months before death. ANDx of PD by FE is feasible based on fetal HCM.
      It promotes early initiation of ERT which may improve outcome in some patients.
      However, larger studies and longer follow-ups are required.

PMID- 20821054
TI  - Determination of cystathionine beta-synthase activity in human plasma by LC
      MS/MS: potential use in diagnosis of CBS deficiency.
AB  - Cystathionine beta-synthase (CBS) deficiency is usually confirmed by assaying the
      enzyme activity in cultured skin fibroblasts. We investigated whether CBS is
      present in human plasma and whether determination of its activity in plasma could
      be used for diagnostic purposes. We developed an assay to measure CBS activity in
      20 MUL of plasma using a stable isotope substrate - 2,3,3-(2)H serine. The
      activity was determined by measurement of the product of enzyme reaction, 3,3
      (2)H-cystathionine, using LC-MS/MS. The median enzyme activity in control plasma
      samples was 404 nmol/h/L (range 66-1,066; n = 57). In pyridoxine nonresponsive
      CBS deficient patients, the median plasma activity was 0 nmol/ho/L (range 0-9; n
      = 26), while in pyridoxine responsive patients the median activity was 16
      nmol/hour/L (range 0-358; n = 28); this overlapped with the enzyme activity from
      control subject. The presence of CBS in human plasma was confirmed by an in
      silico search of the proteome database, and was further evidenced by the
      activation of CBS by S-adenosyl-L-methionine and pyridoxal 5'-phosphate, and by
      configuration of the detected reaction product, 3,3-(2)H-cystathionine, which was
      in agreement with the previously observed CBS reaction mechanism. We hypothesize
      that the CBS enzyme in plasma originates from liver cells, as the plasma CBS
      activities in patients with elevated liver aminotransferase activities were more
      than 30-fold increased. In this study, we have demonstrated that CBS is present
      in human plasma and that its catalytic activity is detectable by LC-MS/MS. CBS
      assay in human plasma brings new possibilities in the diagnosis of pyridoxine
      nonresponsive CBS deficiency.

PMID- 20821055
TI  - Enzyme assay and clinical assessment in subjects with a Chinese hotspot late
      onset Fabry mutation (IVS4 + 919G->A).
AB  - Newborn screening for Fabry disease in Taiwan Chinese has revealed a high
      incidence of the late-onset GLA mutation IVS4 + 919G->A (~1 in 1,500-1,600
      males). We studied 94 adults with this mutation [22 men, 72 women; mean age: men
      57.8 +/- 6.0 (range 42-68), women 39.1 +/- 14.1 years (range 19-82)]. Plasma
      alpha-galactosidase A activity assay was 10.4 +/- 11.2% of normal in the men and
      48.6 +/- 19.5% of normal in the women. Echocardiography in 90 of the adults
      revealed left ventricular hypertrophy (LVH) in 19 (21%), including 14 of 21 men
      (67%) and 5 of 69 women (7%). Microalbuminuria, based on the urine albumin-to
      creatinine ratio measured on at least two occasions, was present in 17 of 86
      subjects (20%) (men: 5/20, 25%; women 12/66, 18%). At least one ocular
      manifestation consistent with Fabry disease was present in 41 of 52 subjects
      (79%) who underwent ophthalmologic examination, including 8 (15%) with
      conjunctival vessel tortuosity, 15 (29%) with cornea verticillata, 10 (19%) with
      Fabry cataract, and 34 (65%) with retinal vessel tortuosity. Among subjects over
      40 years of age, men were more likely than women to have LVH [14/21 (67%) vs 5/25
      (20%), p < 0.001]. Cardiovascular, renal and ocular abnormalities are highly
      prevalent in adult Taiwan Chinese subjects with the Fabry mutation IVS4 + 919G
      >A. Our findings contribute to the limited understanding of the course of this
      late-onset disease variant and underscore the need for close follow up in such
      patients.

PMID- 20821057
TI  - Protective effect of urocortin on 1-methyl-4-phenylpyridinium-induced
      dopaminergic neuronal death.
AB  - Recent studies have indicated that the corticotropin releasing hormone (CRF)
      related peptide, urocortin, restores key indicators of damage in animal models
      for Parkinson's disease (PD). However, the molecular mechanism for the
      neuroprotective effect of urocortin is unknown. 1-Methy-4-phenylpyridinium
      (MPP(+)) induces dopaminergic neuronal death. In the present study, MPP(+)
      induced neuroblastoma SH-SY5Y cell death was significantly attenuated by
      urocortin in a concentration-dependent manner. The protective effect of urocortin
      involved the activation of CRF receptor type 1, resulting in the increase of
      cyclic AMP (cAMP) levels. Various cAMP-enhancing reagents mimicked the effect of
      urocortin, while inhibitors for protein kinase A (PKA) blocked the effect of
      urocortin, strongly implicating the involvement of cAMP-PKA pathway in the
      neuroprotective effect of urocortin on MPP(+)-induced cell death. As the
      downstream of this signal pathway, urocortin promoted phosphorylation of both
      glycogen synthase kinase 3beta and extracellular signal-regulated kinases, which
      are known to promote cell survival. These neuroprotective signaling pathways of
      urocortin may serve as potential therapeutic targets for PD.

PMID- 20821058
TI  - Propofol protects the autophagic cell death induced by the ischemia/reperfusion
      injury in rats.
AB  - Autophagy has been implicated in cardiac cell death during ischemia/reperfusion
      (I/R). In this study we investigated how propofol, an antioxidant widely used for
      anesthesia, affects the autophagic cell death induced by the myocardial I/R
      injury. The infarction size in the myocardium was dramatically reduced in rats
      treated with propofol during I/R compared with untreated rats. A large number of
      autophagic vacuoles were observed in the cardiomyocytes of I/R-injured rats but
      rarely in I/R-injured rats treated with propofol. While LC3-II formation, an
      autophagy marker, was up-regulated in the I/R-injured myocardium, it was
      significantly down-regulated in the myocardial tissues of I/R-injured and
      propofol-treated rats. Moreover, propofol inhibited the I/R-induced expression of
      Beclin-1, and it accelerated phosphorylation of mTOR during I/R and Beclin-1/Bcl
      2 interaction in cells, which indicates that it facilitates the inhibitory
      pathway of autophagy. These data suggest that propofol protects the autophagic
      cell death induced by the myocardial I/R injury.

PMID- 20821056
TI  - The role of the cerebellum in cognition and emotion: personal reflections since
      1982 on the dysmetria of thought hypothesis, and its historical evolution from
      theory to therapy.
AB  - The cognitive neuroscience of the cerebellum is now an established
      multidisciplinary field of investigation. This essay traces the historical
      evolution of this line of inquiry from an emerging field to its current status,
      with personal reflections over almost three decades on this journey of discovery.
      It pays tribute to early investigators who recognized the wider role of the
      cerebellum beyond motor control, traces the origins of new terms and concepts
      including the dysmetria of thought theory, the universal cerebellar transform,
      and the cerebellar cognitive affective syndrome, and places these developments
      within the broader context of the scientific efforts of a growing community of
      cerebellar cognitive neuroscientists. This account considers the converging
      evidence from theoretical, anatomical, physiological, clinical, and functional
      neuroimaging approaches that have resulted in the transition from recognizing the
      cerebellar incorporation into the distributed neural circuits subserving
      cognition and emotion, to a hopeful new era of treatment of neurocognitive and
      neuropsychiatric manifestations of cerebellar diseases, and to cerebellar-based
      interventions for psychiatric disorders.

PMID- 20821059
TI  - Reproductive fitness and dietary choice behavior of the genetic model organism
      Caenorhabditis elegans under semi-natural conditions.
AB  - Laboratory breeding conditions of the model organism C. elegans do not correspond
      with the conditions in its natural soil habitat. To assess the consequences of
      the differences in environmental conditions, the effects of air composition,
      medium and bacterial food on reproductive fitness and/or dietary-choice behavior
      of C. elegans were investigated. The reproductive fitness of C. elegans was
      maximal under oxygen deficiency and not influenced by a high fractional share of
      carbon dioxide. In media approximating natural soil structure, reproductive
      fitness was much lower than in standard laboratory media. In seminatural media,
      the reproductive fitness of C. elegans was low with the standard laboratory food
      bacterium E. coli (gamma-Proteobacteria), but significantly higher with C.
      arvensicola (Bacteroidetes) and B. tropica (beta-Proteobacteria) as food. Dietary
      choice experiments in semi-natural media revealed a low preference of C. elegans
      for E. coli but significantly higher preferences for C. arvensicola and B.
      tropica (among other bacteria). Dietary-choice experiments under quasi-natural
      conditions, which were feasible by fluorescence in situ hybridization (FISH) of
      bacteria, showed a high preference of C. elegans for Cytophaga-Flexibacter
      Bacteroides, Firmicutes, and beta-Proteobacteria, but a low preference for gamma
      Proteobacteria. The results show that data on C. elegans under standard
      laboratory conditions have to be carefully interpreted with respect to their
      biological significance.

PMID- 20821060
TI  - A DNA microarray for identification of selected Korean birds based on
      mitochondrial cytochrome c oxidase I gene sequences.
AB  - DNA barcoding with the gene encoding cytochrome c oxidase I (COI) in the
      mitochondrial genome has been proposed as a standard marker to identify and
      discover animal species. Some migratory wild birds are suspected of transmitting
      avian influenza and pose a threat to aircraft safety because of bird strikes. We
      have previously reported the COI gene sequences of 92 Korean bird species. In the
      present study, we developed a DNA microarray to identify 17 selected bird species
      on the basis of nucleotide diversity. We designed and synthesized 19 specific
      oligonucleotide probes; these probes were arrayed on a silylated glass slide. The
      length of the probes was 19-24 bps. The COI sequences amplified from the tissues
      of the selected birds were labeled with a fluorescent probe for microarray
      hybridization, and unique hybridization patterns were detected for each selected
      species. These patterns may be considered diagnostic patterns for species
      identification. This microarray system will provide a sensitive and a high
      throughput method for identification of Korean birds.

PMID- 20821061
TI  - Neural population modes capture biologically realistic large scale network
      dynamics.
AB  - Large scale brain networks are understood nowadays to underlie the emergence of
      cognitive functions, though the detailed mechanisms are hitherto unknown. The
      challenges in the study of large scale brain networks are amongst others their
      high dimensionality requiring significant computational efforts, the complex
      connectivity across brain areas and the associated transmission delays, as well
      as the stochastic nature of neuronal processes. To decrease the computational
      effort, neurons are clustered into neural masses, which then are approximated by
      reduced descriptions of population dynamics. Here, we implement a neural
      population mode approach (Assisi et al. in Phys. Rev. Lett. 94(1):018106, 2005;
      Stefanescu and Jirsa in PLoS Comput. Biol. 4(11):e1000219, 2008), which
      parsimoniously captures various types of population behavior. We numerically
      demonstrate that the reduced population mode system favorably captures the high
      dimensional dynamics of neuron networks with an architecture involving
      homogeneous local connectivity and a large-scale, fiber-like connection with time
      delay.

PMID- 20821063
TI  - A mechanism for ultra-slow oscillations in the cortical default network.
AB  - When the brain is in its noncognitive "idling" state, functional MRI measurements
      reveal the activation of default cortical networks whose activity is suppressed
      during cognitive processing. This default or background mode is characterized by
      ultra-slow BOLD oscillations (~0.05 Hz), signaling extremely slow cycling in
      cortical metabolic demand across distinct cortical regions. Here we describe a
      model of the cortex which predicts that slow cycling of cortical activity can
      arise naturally as a result of nonlinear interactions between temporal (Hopf) and
      spatial (Turing) instabilities. The Hopf instability is triggered by delays in
      the inhibitory postsynaptic response, while the Turing instability is
      precipitated by increases in the strength of the gap-junction coupling between
      interneurons. We comment on possible implications for slow dendritic computation
      and information processing.

PMID- 20821062
TI  - Nonlinear dynamics of emotion-cognition interaction: when emotion does not
      destroy cognition?
AB  - Emotion (i.e., spontaneous motivation and subsequent implementation of a
      behavior) and cognition (i.e., problem solving by information processing) are
      essential to how we, as humans, respond to changes in our environment. Recent
      studies in cognitive science suggest that emotion and cognition are subserved by
      different, although heavily integrated, neural systems. Understanding the time
      varying relationship of emotion and cognition is a challenging goal with
      important implications for neuroscience. We formulate here the dynamical model of
      emotion-cognition interaction that is based on the following principles: (1) the
      temporal evolution of cognitive and emotion modes are captured by the incoming
      stimuli and competition within and among themselves (competition principle); (2)
      metastable states exist in the unified emotion-cognition phase space; and (3) the
      brain processes information with robust and reproducible transients through the
      sequence of metastable states. Such a model can take advantage of the often
      ignored temporal structure of the emotion-cognition interaction to provide a
      robust and generalizable method for understanding the relationship between brain
      activation and complex human behavior. The mathematical image of the robust and
      reproducible transient dynamics is a Stable Heteroclinic Sequence (SHS), and the
      Stable Heteroclinic Channels (SHCs). These have been hypothesized to be possible
      mechanisms that lead to the sequential transient behavior observed in networks.
      We investigate the modularity of SHCs, i.e., given a SHS and a SHC that is
      supported in one part of a network, we study conditions under which the SHC
      pertaining to the cognition will continue to function in the presence of
      interfering activity with other parts of the network, i.e., emotion.

PMID- 20821064
TI  - Coherent Infomax as a computational goal for neural systems.
AB  - Signal processing in the cerebral cortex is thought to involve a common multi
      purpose algorithm embodied in a canonical cortical micro-circuit that is
      replicated many times over both within and across cortical regions. Operation of
      this algorithm produces widely distributed but coherent and relevant patterns of
      activity. The theory of Coherent Infomax provides a formal specification of the
      objectives of such an algorithm. It also formally derives specifications for both
      the short-term processing dynamics and for the learning rules whereby the
      connection strengths between units in the network can be adapted to the
      environment in which the system finds itself. A central assumption of the theory
      is that the local processors can combine reliable signal coding with flexible use
      of those codes because they have two classes of synaptic connection: driving
      connections which specify the information content of the neural signals, and
      contextual connections which modulate that signal processing. Here, we make the
      biological relevance of this theory more explicit by putting more emphasis upon
      the contextual guidance of ongoing processing, by showing that Coherent Infomax
      is consistent with a particular Bayesian interpretation for the contextual
      guidance of learning and processing, by explicitly specifying rules for on-line
      learning, and by suggesting approximations by which the learning rules can be
      made computationally feasible within systems composed of very many local
      processors.

PMID- 20821065
TI  - Decomposition of neurological multivariate time series by state space modelling.
AB  - Decomposition of multivariate time series data into independent source components
      forms an important part of preprocessing and analysis of time-resolved data in
      neuroscience. We briefly review the available tools for this purpose, such as
      Factor Analysis (FA) and Independent Component Analysis (ICA), then we show how
      linear state space modelling, a methodology from statistical time series
      analysis, can be employed for the same purpose. State space modelling, a
      generalization of classical ARMA modelling, is well suited for exploiting the
      dynamical information encoded in the temporal ordering of time series data, while
      this information remains inaccessible to FA and most ICA algorithms. As a result,
      much more detailed decompositions become possible, and both components with sharp
      power spectrum, such as alpha components, sinusoidal artifacts, or sleep
      spindles, and with broad power spectrum, such as FMRI scanner artifacts or
      epileptic spiking components, can be separated, even in the absence of prior
      information. In addition, three generalizations are discussed, the first relaxing
      the independence assumption, the second introducing non-stationarity of the
      covariance of the noise driving the dynamics, and the third allowing for non
      Gaussianity of the data through a non-linear observation function. Three
      application examples are presented, one electrocardigram time series and two
      electroencephalogram (EEG) time series. The two EEG examples, both from epilepsy
      patients, demonstrate the separation and removal of various artifacts, including
      hum noise and FMRI scanner artifacts, and the identification of sleep spindles,
      epileptic foci, and spiking components. Decompositions obtained by two ICA
      algorithms are shown for comparison.

PMID- 20821066
TI  - Attractor dynamics and thermodynamic analogies in the cerebral cortex:
      synchronous oscillation, the background EEG, and the regulation of attention.
AB  - Ongoing changes in attention and cognition depend upon cortical/subcortical
      interactions, which select sequences of different spatial patterns of activation
      in the cortex. It is proposed that each pattern of cortical activation permits
      evolution of electrocortical wave activity toward statistically stationary
      states, analogous to thermodynamic equilibrium. In each steady-state, neurons
      fire with an intrinsic Poisson spike probability and also with a bursting pattern
      related to network oscillations. Excitatory cell dendrites act as a regenerative
      reservoir in which pulse generation is balanced against dissipations. Equilibria
      exhibit contrasting limits. One limit, at high cortical activation, generates
      widespread zero-lag synchrony among excitatory cells, with partial suppression of
      noise. Excitatory and inhibitory cells approach zero-lag local correlation, with
      1/4 cycle lag-correlation at greater distances of separation. The high-activation
      limit defines a correlated system of attractor basins, capable of co-ordinating
      synaptic modifications and intracortical signal generation. Suppression of noise
      would enhance convergence about attractor basins in the manner of simulated
      annealing, while, conversely, the persistence of some noise prevents network
      paralysis by phase locking. At the opposite limit-that of low activation-spikes
      and waves have low cross- and auto-correlation, but have wide-spectrum
      sensitivity to inputs. It is hypothesised that cortical regions, transiently at
      equilibrium near these extremes, engage in interaction with each other and with
      subcortical systems, to generate ongoing sequences of attention and cognition.
      This account is compatible with classical and recently observed experimental
      phenomena. The principle features inferred from a simplified linear mathematical
      account are reproduced in a more physiologically realistic and non-linear
      numerical simulation.

PMID- 20821067
TI  - Logic in a dynamic brain.
AB  - The ability of the human brain to carry out logical reasoning can be interpreted,
      in general, as a by-product of adaptive capacities of complex neural networks.
      Thus, we seek to base abstract logical operations in the general properties of
      neural networks designed as learning modules. We show that logical operations
      executable by McCulloch-Pitts binary networks can also be programmed in analog
      neural networks built with associative memory modules that process inputs as
      logical gates. These modules can interact among themselves to generate dynamical
      systems that extend the repertoire of logical operations. We demonstrate how the
      operations of the exclusive-OR or the implication appear as outputs of these
      interacting modules. In particular, we provide a model of the exclusive-OR that
      succeeds in evaluating an odd number of options (the exclusive-OR of classical
      logic fails in his case), thus paving the way for a more reasonable biological
      model of this important logical operator. We propose that a brain trained to
      compute can associate a complex logical operation to an orderly structured but
      temporary contingent episode by establishing a codified association among memory
      modules. This explanation offers an interpretation of complex logical processes
      (eventually learned) as associations of contingent events in memorized episodes.
      We suggest, as an example, a cognitive model that describes these "logical
      episodes".

PMID- 20821069
TI  - Liaison neurologists facilitate accurate neurological diagnosis and management,
      resulting in substantial savings in the cost of inpatient care.
AB  - BACKGROUND: Despite understaffing of neurology services in Ireland, the demand
      for liaison neurologist input into the care of hospital inpatients is increasing.
      This aspect of the workload of the neurologist is often under recognised.
      AIMS/METHODS: We prospectively recorded data on referral and service delivery
      patterns to a liaison neurology service, the neurological conditions encountered,
      and the impact of neurology input on patient care. RESULTS: Over a 13-month
      period, 669 consults were audited. Of these, 79% of patients were seen within 48
      h and 86% of patients were assessed by a consultant neurologist before discharge.
      Management was changed in 69% cases, and discharge from hospital expedited in
      50%. If adequate resources for neurological assessment had been available, 28%
      could have been seen as outpatients, with projected savings of 857 bed days.
      CONCLUSIONS: Investment in neurology services would facilitate early accurate
      diagnosis, efficient patient and bed management, with substantial savings.

PMID- 20821070
TI  - Pretreatment of synthetic dairy wastewater using the sophorolipid-producing yeast
      Candida bombicola.
AB  - The presence of high strength fats and oils in dairy industry wastewaters poses
      serious challenges for biological treatment systems, and, therefore, its
      pretreatment is necessary in order to remove them. In the present study,
      synthetic dairy wastewater prepared in the laboratory was pretreated using the
      sophorolipid-producing yeast Candida bombicola in a laboratory-scale bioreactor
      under batch, fed-batch, and continuous modes of operation. To support the yeast
      growth, the wastewater was supplemented with sugarcane molasses (1% w/v) and
      yeast extract (0.1% w/v). Results from the batch operated fermentor revealed
      complete utilization of fats present in the wastewater within 96 h with more than
      93% COD removal efficiency. The yeast was, however, able to pretreat the
      wastewater more quickly and efficiently under fed-batch mode of operation than
      under batch operated condition in the same fermentor. Continuous experiments were
      carried out with a wastewater retention time of 28 h in the reactor; results
      showed very good performance of the system in complete utilization of fats and
      COD removal efficiency of more than 90%. The study proved the excellent potential
      of the biosurfactant-producing yeast in pretreating high-fat- and oil-containing
      dairy industry wastewater.

PMID- 20821071
TI  - Breeding an amylolytic yeast strain for alcoholic beverage production.
AB  - A starch-utilizing, yeast-like fusant was successfully created from fused
      protoplasts of Schizosaccharomyces pombe and Monascus anka, and the feasibility
      of using this fusant as a new strain for alcoholic beverage development was
      reported. The new fusant utilized various carbon sources more efficiently than
      its parent cells did. Rice koji prepared separately by cultivating the fusant and
      its parental strains on rice was compared to explore the effect of yeast strain
      on the production of alpha-amylase, glucoamylase, and acid protease that are
      crucial in wine making using cereal grains. It was found that the fusant produced
      greater levels of the above-mentioned enzymes than its parental strain does.
      Consequently, the usage of this fusant in the alcoholic fermentation of polished
      rice was found to reduce approximately 50% consumption of added glucoamylase than
      when its parental strain was used. Besides, at the end of fermentation, the
      fusant yeast resulted in a mash with distribution of flavor components very
      different from that produced by its parental strains. Thus, the fusant can be
      used as a new yeast strain for creating novel alcoholic beverages.

PMID- 20821072
TI  - In vivo evaluation of cerebral transplantation of resovist-labeled bone marrow
      stromal cells in Parkinson's disease rats using magnetic resonance imaging.
AB  - The effectiveness of Resovist-labeled bone marrow stem cells (BMSCs) was
      evaluated in vivo following their cerebral transplantation in a model of
      Parkinson's disease (PD) in rats using MRI, and the MRI findings were further
      compared with the behavior and histopathological manifestations of these rats.
      Forty PD rats were randomly assigned into five groups according to the cell doses
      injected into the rat brain site: control group (normal saline injection) and
      groups injected with 1 * 10(5), 1.5 * 10(5), 2 * 10(5), and 2.5 * 10(5) BMSCs.
      Gradient echo T2-weighted images were obtained immediately after cell
      transplantation and repeatedly taken 1, 4, 8, and 12 week(s) after cell
      transplantation. The rotational behavior of the animals was observed before and
      1, 4, and 8 week(s) after transplantation. The rats were killed after the last
      MRI scanning, the brain tissues were analyzed by histopathology techniques, and
      RNAs were extracted for the expression analysis of selected genes using RT-PCR.
      One week following cell transplantation, all injected sites showed well-defined
      hypointense areas on MR images, with the most significant effect observed in rats
      injected with 2 * 10(5) BMSCs. These MR findings in PD rats lasted up to 12
      weeks. The effectiveness of BMSC transplantation revealed by MRI was well
      confirmed by the behavioral and histopathological observations as well as
      indirectly supported by gene expression analyses. With the use of SPIO labeling,
      MRI techniques provided a dynamic evaluation of the spatial and temporal changes
      following cell transplantation and allowed the association analysis among the
      imaging, functions, and gene expression analysis in rats. These data also suggest
      the therapeutic potential of transplanted BMSCs. It is reasonable to speculate
      that the use of MRI in in vivo evaluation of the effect and fate of transplanted
      cells in various disease models will be beneficial to developing new strategies
      of cell-based gene therapy.

PMID- 20821073
TI  - Poly-beta-hydroxybutyrate and exopolysaccharide biosynthesis by bacterial
      isolates from pigeonpea [Cajanus cajan (L.) Millsp] root nodules.
AB  - The bacterial strains that are able to produce biopolymers that are applied in
      industrial sectors present a source of renewable resources. Some microorganisms
      are already applied at several industrial sectors, but the prospecting of new
      microbes must bring microorganisms that are feasible to produce interesting
      biopolymers more efficiently and in cheaper conditions. Among the biopolymers
      applied industrially, polyhydroxybutyrate (PHB) and exopolysaccharides (EPS)
      stand out because of its applications, mainly in biodegradable plastic production
      and in food industry, respectively. In this context, the capacity of bacteria
      isolated from pigeonpea root nodules to produce EPS and PHB was evaluated, as
      well as the cultural characterization of these isolates. Among the 38 isolates
      evaluated, the majority presented fast growth and ability to acidify the culture
      media. Regarding the biopolymer production, five isolates produced more than 10
      mg PHB per liter of culture medium. Six EPS producing bacteria achieved more than
      200 mg EPS per liter of culture medium. Evaluating different carbon sources, the
      PHB productivity of the isolate 24.6b reached 69% of cell dry weight when
      cultured with starch as sole carbon source, and the isolate 8.1c synthesized 53%
      PHB in dry cell biomass and more than 1.3 g L-1 of EPS when grown using xylose as
      sole carbon source.

PMID- 20821074
TI  - Association study of interferon gamma (IFN-gamma) +874T/A gene polymorphism in
      patients with paranoid schizophrenia.
AB  - Schizophrenia is a multifactorial disease with changes affecting the immune
      system. Dysregulation of the cytokine network in schizophrenia has been well
      documented. Such changes may occur due to disturbances in cytokine levels that
      are linked to polymorphisms of cytokine genes. However, research in the role of
      cytokine gene polymorphisms in schizophrenia has been surprisingly scanty. The
      aim of this study was to identify, in a case control study, whether polymorphism
      of IFN-gamma gene is a risk factor for the development of paranoid schizophrenia.
      To the best of our knowledge, this is the first study that examines the
      association between the IFN-gamma gene polymorphism and psychopathological
      symptoms in patients with paranoid schizophrenia. Polymorphism of IFN-gamma
      (+874T/A, rs 62559044) in schizophrenic patients (n=179), as well as healthy
      individuals (n=196), both Polish residents, was genotyped using AS-PCR method. Of
      note, when analyzing the results, we took into consideration the gender of
      studied individuals. Surprisingly, a single-nucleotide polymorphism in the first
      intron of the IFN-gamma gene was found to be associated with paranoid
      schizophrenia in males, but not in females. The presence of allele A at position
      +874 in the IFN-gamma gene correlates with 1.66-fold higher risk of paranoid
      schizophrenia development in males. Differences in the genotypes may have an
      important role in determining the level of I gene transcription. Because other
      polymorphisms have been demonstrated to influence IFN-gamma transcription,
      further analysis is necessary to clarify the role of this gene in the
      pathogenesis of paranoid schizophrenia.

PMID- 20821075
TI  - PAC1 deficiency in a murine model induces gastric mucosa hypertrophy and higher
      basal gastric acid output.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to
      increase the histamine release from gastric enterochromaffin-like (ECL) cells and
      promote gastric acid secretion in rats. In contrast, in mice, PACAP has been
      demonstrated to induce a decrease of gastric acid secretion, an effect presumably
      due to somatostatin release. To more clearly define the role of PACAP in the
      regulation of gastric acid output, a knockout mouse model for the PACAP-specific
      receptor PAC1 was applied in this study. Measurements of the basal and stimulated
      gastric acid secretion and morphological studies on the gastric mucosa were
      performed in both wild-type and PAC1-deficient mice. Compared with the wild-type
      mice, the PAC1-deficient mice showed a nearly threefold higher basal gastric acid
      output, increased gastric mucosa thickness and glands height, and proportional
      increases in parietal and total cell counts in the gastric mucosa. The PAC1
      deficient mice also showed a trend of increased plasma gastrin levels and gastrin
      gene expression in the gastric mucosa. This study indicates that the expression
      of PAC1 is clearly important for maintaining the homeostasis of gastric acid
      secretion. Loss of PACAP receptor during development may lead to a compensatory
      mechanism regulating gastric acid secretion.

PMID- 20821076
TI  - Human multipotent mesenchymal stromal cells from distinct sources show different
      in vivo potential to differentiate into muscle cells when injected in dystrophic
      mice.
AB  - Limb-girdle muscular dystrophies are a heterogeneous group of disorders
      characterized by progressive degeneration of skeletal muscle caused by the
      absence or deficiency of muscle proteins. The murine model of Limb-Girdle
      Muscular Dystrophy 2B, the SJL mice, carries a deletion in the dysferlin gene.
      Functionally, this mouse model shows discrete muscle weakness, starting at the
      age of 4-6 weeks. The possibility to restore the expression of the defective
      protein and improve muscular performance by cell therapy is a promising approach
      for the future treatment of progressive muscular dystrophies (PMD). We and others
      have recently shown that human adipose multipotent mesenchymal stromal cells
      (hASCs) can differentiate into skeletal muscle when in contact with dystrophic
      muscle cells in vitro and in vivo. Umbilical cord tissue and adipose tissue are
      known rich sources of multipotent mesenchymal stromal cells (MSCs), widely used
      for cell-based therapy studies. The main objective of the present study is to
      evaluate if MSCs from these two different sources have the same potential to
      reach and differentiate in muscle cells in vivo or if this capability is
      influenced by the niche from where they were obtained. In order to address this
      question we injected human derived umbilical cord tissue MSCs (hUCT MSCs) into
      the caudal vein of SJL mice with the same protocol previously used for hASCs; we
      evaluated the ability of these cells to engraft into recipient dystrophic muscle
      after systemic delivery, to express human muscle proteins in the dystrophic host
      and their effect in functional performance. These results are of great interest
      for future therapeutic application.

PMID- 20821077
TI  - Should all hypertensive dialysis patients receive a blocker of the Renin
      Angiotensin system?
AB  - Cardiovascular mortality and hypertension remain common in the dialysis
      population, and two recent meta-analyses have suggested that antihypertensive
      pharmacotherapy reduces cardiovascular events in dialysis patients. Based on
      their benefits in other populations, blockers of the renin-angiotensin
      aldosterone system (RAAS) are an attractive treatment option. The evidence that
      RAAS blockers improve surrogate end points is mixed. However, a recent meta
      analysis found significant improvement in left ventricular mass with RAAS
      blocking drugs in hemodialysis patients. Only a few trials have examined RAAS
      blocking drugs and cardiovascular events in dialysis patients, and a recent meta
      analysis found no significant benefit in hemodialysis patients. The single trial
      of peritoneal dialysis patients that reported cardiovascular events found no
      benefit from RAAS blockers. Fortunately, the risk of hyperkalemia appears low.
      Based on the available evidence, we cannot categorically recommend that all
      hypertensive dialysis patients be treated with RAAS blockers. We await the
      results of adequately powered clinical trials.

PMID- 20821078
TI  - Is the magnesium era for aneurysmal subarachnoid hemorrhage over?

PMID- 20821079
TI  - Update on the mechanisms of gastric acid secretion.
AB  - Acid-related disorders represent a major healthcare concern. In recent years, our
      understanding of the physiologic processes underlying gastric acid secretion has
      improved notably. The identity of several apical ion transport proteins, which
      are necessary for acid secretion to take place, has been resolved. The recent
      developments have uncovered potential therapeutic targets for the treatment of
      acid-related disorders. This brief review provides an update on the mechanisms of
      gastric acid secretion, with a particular focus on apical ion transport.

PMID- 20821080
TI  - The fault is not in ourselves, but in our methods: comment on Schwarz.
AB  - Schwarz is right to question the methodological foundations of much of
      contemporary personality research. I argue that he does not go far enough, opting
      instead to salvage the psychometric tradition for research it cannot possibly
      accomplish, namely the understanding of persons in an evolutionary and historical
      context. Furthermore he does not address the question of measurement that has
      bedeviled the discipline. For all its historical tenacity, the psychometric
      tradition has been good at classification but weak at understanding, explanation,
      or description of the phenomena that most interest psychologists.

PMID- 20821081
TI  - Perturbation correction factors for cylindrical ionization chambers in high
      energy electron beams.
AB  - The aim of the study was to evaluate the perturbation correction factors at a
      reference depth for cylindrical ionization chambers in high-energy electron beams
      by means of the EGSnrc Monte Carlo user code cavity. The cylindrical chambers
      used in this study were the Farmer-type of PTW30010, PTW30011, PTW30012, and
      PTW30013 models. We calculated the wall correction factor, P (wall), the cavity
      or electron fluence correction factor, P (cav), the stem correction factor, P
      (stem), the central electrode correction factor, P (cel), and the overall
      perturbation correction factor, P (Q), for each chamber. The calculated P (cav)
      values were higher by from 2 to 1% than those recommended by the IAEA-TRS-398
      code of practice, in an energy range of 6-18 MeV. The P (wall) values almost
      agreed with the analytical calculation performed with IAEA-TRS-398. The P (cel)
      values agreed with those of Ma and Nahum, performed with IAEA-TRS-398. The P
      (stem) values were approximately 0.995 on average and were independent of the
      electron beam energy. P (stem) needs to be considered in future dosimetry
      protocols. The P (Q) values were higher from 1 to 2% than those of IAEA-TRS-398
      in an energy range of 6-18 MeV.

PMID- 20821082
TI  - Nationwide survey on the operational status of electron accelerators for
      radiation therapy in Japan.
AB  - A nationwide survey was conducted on electron accelerators for radiation therapy
      in Japan for obtaining fundamental data on the actual operational situation of
      these accelerators. The research subjects were all medical institutions equipped
      with electron accelerators for radiation therapy (874 accelerators) in Japan.
      Postcards explaining the purpose and procedure of the survey were sent to each
      institution. Each institution was requested to download a questionnaire from the
      website and return it by e-mail. We obtained the following results. Energy: about
      90% of the accelerators did not exceed 10 MeV as the permitted maximum energy.
      Beam intensity: a total of 94% of the accelerators did not exceed 4 Gy/min as the
      mean exposure dose rate. Beam time: a total of 74% of the accelerators were below
      half of the permitted maximum beam time. However, 2% of the accelerators exceeded
      90% of the permitted maximum time. Cumulative dose: about 10% of institutions
      obtained permission not to use the maximum beam time, but to use the maximum
      cumulative dose to secure sufficient beam time. From these results, it became
      clear that the induced radioactivity based on the maximum beam current and the
      maximum operating time under an official permit would be overestimated.
      Therefore, the neutron dose should be assessed by use of a daily operational
      record, not from an official permit.

PMID- 20821083
TI  - Evaluation of the usefulness of a MOSFET detector in an anthropomorphic phantom
      for 6-MV photon beam.
AB  - In order to evaluate the usefulness of a metal oxide-silicon field-effect
      transistor (MOSFET) detector as a in vivo dosimeter, we performed in vivo
      dosimetry using the MOSFET detector with an anthropomorphic phantom. We used the
      RANDO phantom as an anthropomorphic phantom, and dose measurements were carried
      out in the abdominal, thoracic, and head and neck regions for simple square field
      sizes of 10 x 10, 5 x 5, and 3 x 3 cm(2) with a 6-MV photon beam. The dose
      measured by the MOSFET detector was verified by the dose calculations of the
      superposition (SP) algorithm in the XiO radiotherapy treatment-planning system.
      In most cases, the measured doses agreed with the results of the SP algorithm
      within +/-3%. Our results demonstrated the utility of the MOSFET detector for in
      vivo dosimetry even in the presence of clinical tissue inhomogeneities.

PMID- 20821084
TI  - A study on the validity of quantitative ultrasonic measurement used the bone
      mineral density values on dual-energy X-ray absorptiometry in young and in middle
      aged or older women.
AB  - The influence of age and physique on dual-energy X-ray absorptiometry (DXA) and
      quantitative ultrasound (QUS) was investigated in young, middle-aged, and older
      women. The validity of the bilateral calcaneal QUS values was investigated
      regarding the bone mineral density (BMD) values on DXA of the lumbar spine, left
      femoral neck, and left femur as the optimal standards. The subjects were 55 young
      women (19.6 +/- 1.0 years), and 152 middle-aged and older women (62.9 +/- 7.2
      years). The BMD on DXA was significantly correlated with the bone strength on QUS
      in both young and middle-aged or older women, but the positive likelihood ratios
      of the standard QUS values recommended by the manufacturer to the optimum
      standards on DXA were low, suggesting that osteoporosis cannot be diagnosed or
      predicted by use of the QUS method. Combination with DXA is necessary, such as
      primary screening by QUS followed by secondary screening by DXA.

PMID- 20821085
TI  - Effects of inversion and saturation times on relationships between contrast agent
      concentrations and signal intensities of T1-weighted magnetic resonance images.
AB  - The present study was an attempt to investigate the effect of variation of
      inversion time (T (I)) and saturation time (T (S)) on the linear relationship
      between contrast agent concentration and signal intensity (SI) on Turbo Fast Low
      Angle Shot (TurboFLASH) T (1)-weighted images in MRI. For this purpose, inversion
      recovery (IR) and saturation recovery (SR) sequences (Center out Phase-Encoding
      acquisition) were used. A phantom was designed to hold 25 vials which contained
      either different (between 0 and 19.77 mmol/L) or constant (1.20 mmol/L)
      concentrations of contrast agent. The vials of constant concentration were used
      for the measurement of coil non-uniformity, which was normalized to give a
      correction factor. The vials of different concentrations were used to measure the
      SI by using different sequences and different T (I) and T (S) values. To
      calculate the corrected SI for different concentrations, we multiplied the SI of
      each vial by its correction factor. The relationships between the corrected SI
      and the concentration [were evaluated], where the threshold of (R (2) = 0.95 and
      0.99) was maintained. This study shows that different sequences and different T
      (I) and T (S) values can have an effect on the correlation between the SI and
      concentration. Regardless of the values of T (I), T (S), and the different IR and
      SR sequences chosen, the linear relationship between the SI and concentration was
      about twice that previously reported (i.e., 0.8 mmol/L, R (2) = 0.95).

PMID- 20821086
TI  - Demonstration of iodine K-edge imaging by use of an energy-discrimination X-ray
      computed tomography system with a cadmium telluride detector.
AB  - An energy-discrimination K-edge X-ray computed tomography (CT) system is useful
      for increasing the contrast resolution of a target region by utilizing contrast
      media. The CT system has a cadmium telluride (CdTe) detector, and a projection
      curve is obtained by linear scanning with use of the CdTe detector in conjunction
      with an X-stage. An object is rotated by a rotation step angle with use of a
      turntable between the linear scans. Thus, CT is carried out by repetition of the
      linear scanning and the rotation of an object. Penetrating X-ray photons from the
      object are detected by the CdTe detector, and event signals of X-ray photons are
      produced with use of charge-sensitive and shaping amplifiers. Both the photon
      energy and the energy width are selected by use of a multi-channel analyzer, and
      the number of photons is counted by a counter card. For performing energy
      discrimination, a low-dose-rate X-ray generator for photon counting was
      developed; the maximum tube voltage and the minimum tube current were 110 kV and
      1.0 microA, respectively. In energy-discrimination CT, the tube voltage and the
      current were 60 kV and 20.0 microA, respectively, and the X-ray intensity was
      0.735 microGy/s at 1.0 m from the source and with a tube voltage of 60 kV.
      Demonstration of enhanced iodine K-edge X-ray CT was carried out by selection of
      photons with energies just beyond the iodine K-edge energy of 33.2 keV.

PMID- 20821087
TI  - Investigation of errors by radiological technologists and evaluation of
      preventive measures: general and mobile X-ray examinations.
AB  - The first objective in this study was to identify the errors of incidents and
      accidents that occurred in general and mobile X-ray examinations. Based on the
      analysis of results, the second purpose in this study was to propose useful
      measures to prevent such errors. As much as 553 radiological technologists in the
      Gunma Prefecture were surveyed on their experience with errors related to general
      and mobile X-ray examinations. The questionnaire asked for descriptions of errors
      experienced during examinations and the responses given (multiple answers
      possible), and evaluations of the degree of busyness on a five-point scale. A
      total of 115 questionnaires were returned. Analysis revealed that there was no
      significant relationship between errors and degree of busyness for either general
      or mobile examinations. The most frequent error both in general and in mobile
      examinations was to X-ray a patient mistakenly, the cause of which was cited as
      failure to confirm the patient's name. After the use of solution priority number
      to evaluate proposed preventive measures, such as finger-pointing and call,
      independent double-checks, and verbal self-confirmation would be the simplest and
      most easily implemented countermeasure.

PMID- 20821088
TI  - Microdosimetric investigation of the spectra from YAYOI by use of the Monte Carlo
      code PHITS.
AB  - The purpose of this study was to obtain the neutron energy spectrum on the
      surface of the moderator of the Tokyo University reactor YAYOI and to investigate
      the origins of peaks observed in the neutron energy spectrum by use of the Monte
      Carlo Code PHITS for evaluating biological studies. The moderator system was
      modeled with the use of details from an article that reported a calculation
      result and a measurement result for a neutron spectrum on the surface of the
      moderator of the reactor. Our calculation results with PHITS were compared to
      those obtained with the discrete ordinate code ANISN described in the article. In
      addition, the changes in the neutron spectrum at the boundaries of materials in
      the moderator system were examined with PHITS. Also, microdosimetric energy
      distributions of secondary charged particles from neutron recoil or reaction were
      calculated by use of PHITS and compared with a microdosimetric experiment. Our
      calculations of the neutron energy spectrum with PHITS showed good agreement with
      the results of ANISN in terms of the energy and structure of the peaks. However,
      the microdosimetric dose distribution spectrum with PHITS showed a remarkable
      discrepancy with the experimental one. The experimental spectrum could not be
      explained by PHITS when we used neutron beams of two mono-energies.

PMID- 20821089
TI  - Three-dimensional motion study of femur, tibia, and patella at the knee joint
      from bi-plane fluoroscopy and CT images.
AB  - In diagnosis and treatment of knee joint diseases, it is effective to study the
      three-dimensional (3D) motion of the patient's knee joint involving the femur,
      tibia, and patella. A 2D/3D registration method with use of fluoroscopy and CT
      images is promising for this purpose. However, there is no report showing whether
      the dynamic 3D motion of the patella can be obtained. In this study, we tried to
      examine dynamic 3D motion of the knee joint which included the patella. First, in
      order to investigate the accuracy of the position estimation, we conducted an
      experiment on a pig knee joint which had several fiducial markers placed on it,
      and we found that errors in the estimation of rotation and translation were less
      than 1 mm and 1 deg. We then carried out an image-acquisition experiment with
      healthy knee joints of three volunteers and confirmed that 3D motions of the
      femur, tibia, and patella were successfully obtained for all cases.

PMID- 20821090
TI  - The perturbation correction factors for cylindrical ionization chambers in high
      energy photon beams.
AB  - In this study, we calculated perturbation correction factors for cylindrical
      ionization chambers in high-energy photon beams by using Monte Carlo simulations.
      We modeled four Farmer-type cylindrical chambers with the EGSnrc/Cavity code and
      calculated the cavity or electron fluence correction factor, P (cav), the
      displacement correction factor, P (dis), the wall correction factor, P (wall),
      the stem correction factor, P (stem), the central electrode correction factor, P
      (cel), and the overall perturbation correction factor, P (Q). The calculated P
      (dis) values for PTW30010/30013 chambers were 0.9967 +/- 0.0017, 0.9983 +/-
      0.0019, and 0.9980 +/- 0.0019, respectively, for (60)Co, 4 MV, and 10 MV photon
      beams. The value for a (60)Co beam was about 1.0% higher than the 0.988 value
      recommended by the IAEA TRS-398 protocol. The P (dis) values had a substantial
      discrepancy compared to those of IAEA TRS-398 and AAPM TG-51 at all photon
      energies. The P (wall) values were from 0.9994 +/- 0.0020 to 1.0031 +/- 0.0020
      for PTW30010 and from 0.9961 +/- 0.0018 to 0.9991 +/- 0.0017 for PTW30011/30012,
      in the range of (60)Co-10 MV. The P (wall) values for PTW30011/30012 were around
      0.3% lower than those of the IAEA TRS-398. Also, the chamber response with and
      without a 1 mm PMMA water-proofing sleeve agreed within their combined
      uncertainty. The calculated P (stem) values ranged from 0.9945 +/- 0.0014 to
      0.9965 +/- 0.0014, but they are not considered in current dosimetry protocols.
      The values were no significant difference on beam qualities. P (cel) for a 1 mm
      aluminum electrode agreed within 0.3% with that of IAEA TRS-398. The overall
      perturbation factors agreed within 0.4% with those for IAEA TRS-398.

PMID- 20821091
TI  - Optimization of dual electron multileaf collimator materials by use of EGSnrc.
AB  - A dual electron multileaf collimator (eMLC) has recently been proposed and
      ascertained to be effective in the collimation of therapy electron beams. The
      EGSnrc Monte Carlo code has been used in the optimization of the dual eMLC by
      simulation of the Varian 2100C medical linear accelerator with the applicator
      completely replaced by the dual eMLC, and calculation of the dose distributions
      in a water phantom. The planar fluence results showed that the material
      combination of 2-cm-thick brass and 2-cm-thick tungsten (eMLCT1) as upper and
      lower eMLCs, respectively, offers minimal radiation leakage outside the treatment
      field. Dose calculation results used in estimation of the maximum dose, depth of
      the maximum dose, surface dose, bremsstrahlung background, and penumbra indicate
      that eMLCT1 offers better beam qualities than do the other dual eMLCs that were
      considered. Maximum optimization was obtained with the dual eMLC designed such
      that the material of the lower eMLC had a higher density than that of the upper
      eMLC.

PMID- 20821092
TI  - Quantitative analysis of ontology research articles in the radiologic domain.
AB  - To investigate the most advanced ontology research in health care and its impact
      on the radiologic domain, we proposed a concept identification and abstraction
      technique called "Concept Step". This technique identifies a MeSH term, medical
      subject headings used in PubMed, in a sentence and climbs up through its
      hierarchy to reach an abstract concept. We developed original Java software to
      implement this technique. We tested it on 2,774 abstracts in health-care ontology
      research retrieved from MEDLINE on 23 October 2008. The total number of MeSH
      terms was 112,690. We counted a total of 33 MeSH terms (0.029%) in the radiologic
      domain. The most frequently occurring term was "radiology", which occurred 21
      times in the article set. Other frequent terms were "magnetic resonance imaging"
      and "tomography", the counts of which were 4 and 3, respectively. A pair plot
      showed no correlation among the MeSH categories "Analytical Diagnostic and
      Therapeutic Techniques and Equipment", "Anatomy", "Biological Sciences", and
      "Chemicals and Drugs". We conclude that ontology research is well established in
      the biomedical domain, and that further study is required in the radiologic
      domain.

PMID- 20821093
TI  - Comparison of detectability of a simple object with low contrast displayed on a
      high-brightness color LCD and a monochrome LCD.
AB  - The goal of this study was to investigate the effect of the different luminance
      settings of a high-brightness color liquid-crystal display (LCD) on the
      detectability of a simple grayscale object with low contrast by use of receiver
      operating characteristic (ROC) analysis. The detectability of a high-brightness
      color LCD with two maximum-luminance settings (500 and 170 cd/m(2)) was compared
      with the detectability of a monochrome LCD (500 cd/m(2)). The two LCDs used in
      this study were calibrated to the grayscale standard display function. The
      average areas under the ROC curve (AUCs) and the standard deviations for all
      thirteen observers for the 500 cd/m(2) color LCD, 500 cd/m(2) monochrome LCD, and
      170 cd/m(2) color LCD were 0.937 +/- 0.040, 0.924 +/- 0.056, and 0.915 +/- 0.068,
      respectively. There were no statistically significant differences in the average
      AUCs among the three LCD monitor conditions. On the other hand, the total
      observation time for the 170 cd/m(2) color LCD was significantly shorter than
      that for the 500 cd/m(2) color and monochrome LCDs (p < 0.05). Irrespective of
      the maximum luminance settings (500 and 170 cd/m(2)), the color LCD provided a
      performance comparable to the monochrome LCD for detection of a simple grayscale
      object with low contrast.

PMID- 20821095
TI  - Creation and application of three-dimensional computer-graphic animations for
      introduction to radiological physics and technology.
AB  - Physics-related subjects are important in the educational fields of radiological
      physics and technology. However, conventional teaching tools, for example texts,
      equations, and two-dimensional figures, are not very effective in attracting the
      interest of students. Therefore, we have created several multimedia educational
      materials covering radiological physics and technology. Each educational
      presentation includes several segments of high-quality computer-graphic
      animations designed to attract students' interest. We used personal computers
      (PCs) and commercial software to create and compile these. Undergraduate and
      graduate students and teachers and related professionals contributed to the
      design and creation of the educational materials as part of student research. The
      educational materials can be displayed on a PC monitor and manipulated with
      popular free software. Opinion surveys conducted in undergraduate courses at
      Kitasato University support the effectiveness of our educational tools in helping
      students gain a better understanding of the subjects offered and in raising their
      interest.

PMID- 20821096
TI  - Detectability of a lung nodule displayed on a liquid-crystal display monitor with
      different maximum luminance settings.
AB  - Our purpose in this study was to examine the detectability of a lung nodule at
      different maximum luminance settings of a liquid-crystal display (LCD) monitor by
      utilizing receiver operating characteristic (ROC) analysis. The LCD monitor used
      in this study was calibrated to the grayscale standard display function with
      different maximum luminance settings (670, 450, and 170 cd/m(2)). The average
      area under the ROC curve (AUC) and the standard deviation for all observers at
      670, 450, and 170 cd/m(2) were 0.837 +/- 0.076, 0.832 +/- 0.051, and 0.830 +/-
      0.078, respectively. There was no statistically significant difference in AUC as
      a function of the maximum luminance setting of the LCD monitor. Considering the
      results, setting the maximum luminance of an LCD monitor at a higher level may
      not provide a significant advantage in the detectability of a lung nodule.

PMID- 20821097
TI  - A parameter study of pencil beam proton dose distributions for the treatment of
      ocular melanoma utilizing spot scanning.
AB  - The results of Monte Carlo calculated dose distributions of proton treatment of
      ocular melanoma are presented. An efficient spot scanning method utilizing active
      energy modulation, which also minimizes the number of target spots was developed.
      We simulated various parameter values for the particle energy spread and the
      pencil beam diameter in order to determine values suitable for medical treatment.
      We found that a 2.5-mm-diameter proton beam with a 5% Gaussian energy spread was
      suitable for treatment of ocular melanoma while preserving vision for the typical
      case that we simulated. The energy spectra and the required proton current were
      also calculated and are reported. The results are intended to serve as a
      guideline for a new class of low-cost, compact accelerators.

PMID- 20821098
TI  - Practical approaches to four-dimensional heavy-charged-particle lung therapy.
AB  - We have developed new design algorithms for compensating boli to facilitate the
      implementation of four-dimensional charged-particle lung therapy in clinical
      applications. Four-dimensional CT (4DCT) data for eight lung cancer patients were
      acquired with a 16-slice CT under free breathing. Six compensating boli were
      developed that may be categorized into three classes: (1) boli-based on contoured
      gross tumor volumes (GTV) from a 4DCT data set during each respiratory phase,
      subsequently combined into one (GTV-4DCT bolus); (2) boli-based on contoured
      internal target volume (ITV) from image-processed 3DCT data only [temporal
      maximum-intensity-projection (TMIP)/temporal-average-intensity-projection (TAIP)]
      with calculated boli (ITV-TMIP and ITV-TAIP boli); and (3) boli-based on
      contoured ITV utilizing image-processed 3DCT data, applied to 4DCT for design of
      boli for each phase, which were then combined. The carbon beam dose distribution
      within each bolus was calculated as a function of time and compared to plans in
      which respiratory-ungated/gated strategies were used. The GTV-4DCT treatment plan
      required a prohibitively long time for contouring the GTV manually for each
      respiratory phase, but it delivered more than 95% of the prescribed dose to the
      target volume. The TMIP and TAIP treatments, although more time-efficient,
      resulted in an unacceptable excess dose to normal tissues and underdosing of the
      target volume. The dose distribution for the ITV-4DCT bolus was similar to that
      for the GTV-4DCT bolus and required significantly less practitioner time. The ITV
      4DCT bolus treatment plan is time-efficient and provides a high-quality dose
      distribution, making it a practical alternative to the GTV-4DCT bolus treatment
      plan.

PMID- 20821099
TI  - Measurement of absorbed doses in organs of medical staff at (18)F-FDG pet
      examination.
AB  - In this study, the organ doses were measured using a human- body phantom
      simulating a medical staff member, and we considered an effective method for
      decreasing exposure to staff in positron emission tomography examinations. A
      fluorescence glass dosimeter was arranged for measurements in various organs.
      Regarding exposure, the average ratio of the dose at 100 cm from the source to
      the dose at 30 cm was 0.35. The ratio of the dose at 100 cm with a 3 cm lead
      shield to the dose at 100 cm with no shielding device was 0.01. To reduce the
      radiation exposure effectively, medical staff members should inform the patient
      of the details of the examination in advance, reduce the contact time with the
      patient during the examination, and maximize their distance from the patient when
      contact is necessary.

PMID- 20821100
TI  - Development of pulmonary blood flow evaluation method with a dynamic flat-panel
      detector: quantitative correlation analysis with findings on perfusion scan.
AB  - Pulmonary blood flow is reflected in dynamic chest radiographs as changes in X
      ray translucency, i.e., pixel values. Thus, decreased blood flow should be
      observed as a reduction of the variation of X-ray translucency. We performed the
      present study to investigate the feasibility of pulmonary blood flow evaluation
      with a dynamic flat-panel detector (FPD). Sequential chest radiographs of 14
      subjects were obtained with a dynamic FPD system. The changes in pixel value in
      each local area were measured and mapped on the original image by use of a gray
      scale in which small and large changes were shown in white and black,
      respectively. The resulting images were compared to the findings in perfusion
      scans. The cross-correlation coefficients of the changes in pixel value and
      radioactivity counts in each local area were also computed. In all patients,
      pulmonary blood flow disorder was indicated as a reduction of changes in pixel
      values on the mapping image, and a correlation was observed between the
      distribution of changes in pixel value and those in radioactivity counts (0.7
      <or= r, 3 cases; 0.4 <or= r < 0.7, 7 cases; 0.2 <or= r < 0.4, 4 cases). The
      results indicated that the distribution of changes in pixel value could provide a
      relative measure related to pulmonary blood flow. The present method is
      potentially useful for evaluating pulmonary blood flow as an additional
      examination in conventional chest radiography.

PMID- 20821101
TI  - Patient setup verification procedure for a portal image in a computed radiography
      system with a high-resolution liquid-crystal display monitor.
AB  - In our conventional visual inspection for setup verification, we have routinely
      used a console monitor of a CR system and a monitor of a treatment-planning
      system (i.e., the separate-monitor method) in order to avoid the need for CR
      portal-film generation. However, the separate-monitor method provided
      insufficient precision in detecting setup errors. We devised a setup verification
      procedure that uses a high-resolution liquid-crystal display monitor (i.e., the
      single-monitor method). Our objective in the present study was to evaluate the
      precision of the single-monitor method. These two methods were compared in terms
      of the precision of visual inspection. The single-monitor method was
      significantly superior to the separate-monitor method in sensitivity and in the
      magnitude of the discrepancy that could not be detected. The single-monitor
      method provides higher precision in visual inspection than does the separate
      monitor method, and is a useful verification procedure.

PMID- 20821102
TI  - Evaluation of a real-time semiconductor dosimeter and measurement of finger dose
      in nuclear medicine departments.
AB  - In this study, the nuclear medicine staff wore one finger dosimeter placed at the
      base of the index finger of the working hand. When a physician injected
      radioisotope drugs, the finger dose was 22.4 microSv, that for radiological
      technologists handling (99m)Tc was 29.6 microSv/day (consultation period 20
      days), that for a physician injecting (18)F-FDG-PET drugs was 51.3 microSv (right
      finger 53.9 microSv, left finger 47.2 microSv), that for pharmacists' assay of
      FDG was 31.5 microSv, and that for radiological technologists positioning
      patients was 1.9 microSv. The largest value (94.1 microSv) was observed in
      physicians in the case of aspiration of a delivered drug. The finger dosimeter
      provides an effective solution for radiation protection procedures and follow-up.
      All the above staff members are on rotation and do not constantly handle
      radioactivity throughout the year.

PMID- 20821103
TI  - A treatment planning strategy for heavy-charged-particle radiotherapy of lung
      cancer by the use of computed tomography with projection data-based temporal
      maximum-intensity projection.
AB  - To design a range-compensating bolus for heavy-charged-particle radiotherapy of
      lung cancer, we propose an image-processing method that uses CT projection data
      for treatment planning. We studied six lung cancer patients in 4DCT mode. Three
      types of range-compensating bolus were designed with use of (1) each bolus for
      4DCT images, (2) image-based maximum-intensity projection data (4DIM), and (3) CT
      images reconstructed by the use of maximum-attenuation projection data (4DPM)
      along the time axis around exhale (=respiratory-gated treatment). Carbon-ion dose
      distributions were calculated by the use of these designed range-compensating
      boluses and were compared. The dose distribution with 4DIM caused overdosing
      beyond the target. However, the dose distribution with 4DPM was similar to that
      with a composite of the range-compensating bolus (CCB) designed for the
      respiratory phases. Furthermore, the volume of the receiving dose for >95% (D95)
      for CTV and the volume of the lung receiving dose for >20 GyE (V20) with 4DPM
      were similar to that with the CCB. The range-compensating bolus with 4DPM
      provides dose distributions similar to that with the CCB in peripheral lung
      cancer and improves the calculating efficiency over CCB.

PMID- 20821104
TI  - Effects of ambient-light correction in luminance measurements of liquid-crystal
      display monitors by use of a telescopic-type luminance meter.
AB  - The quality control of liquid-crystal display (LCD) monitors has become one of
      the important topics for maintaining reliable soft-copy readings in the
      interpretation of diagnostic images. In this paper, the effects of correction in
      the luminance measurement of an LCD monitor by use of a telescopic-type luminance
      meter were investigated. The luminance of the LCD monitor in different ambient
      lighting conditions was measured and compared to the results obtained with no
      ambient lighting (0 lux). The reproducibility of luminance measurements and
      luminance ratios without a baffled tube was lower than those measured with the
      baffled tube due to the effect of ambient light. These tendencies were obvious at
      a relatively low luminance. The correction method by subtraction of the reflected
      ambient light on the surface of the LCD monitor and the stray light of the
      telescopic-type luminance meter from the measured luminance was examined. We
      found that the correction was able to bring the luminance close to that measured
      with the baffled tube.

PMID- 20821105
TI  - Preliminary investigation of the clinical usefulness of super-high-resolution
      LCDs with 9 and 15 mega-sub-pixels: observation studies with phantoms.
AB  - Our purpose in this study was to evaluate the preliminary clinical efficacy of
      soft-copy reading of digital mammography, for a 15-mega-sub-pixel (MsP) and a 9
      MsP super-high-resolution liquid-crystal display (SHR-LCD) by use of an
      independent sub-pixel driving technology. We performed three kinds of phantom
      observation studies by six radiological technologists. Detectability of a
      contrast-detail phantom and simulated small objects (SSOs) resembling
      microcalcifications (MCLs), and shape discrimination ability of SSOs with round
      and square shapes, were examined and compared with a 5-MP conventional LCD (5-MP
      LCD). In each study, four types of display magnification ratio were used. The
      detectability and the shape discrimination ability of the 15-MsP SHR-LCD were
      highest among the three LCDs of most of the display magnification ratios. The 9
      MsP SHR-LCD indicated a higher or equal performance as compared with the 5-MP LCD
      in the SSO detection and shape studies. The results of our study demonstrated
      that the SHR-LCDs had good potential to detect MCLs and to evaluate the shape in
      high-resolution digital mammography.

PMID- 20821106
TI  - The optimal cardiac phase for detecting the thrombi of the left atrial appendage
      on multi-slice computed tomography in patients with atrial fibrillation.
AB  - We evaluated patients with atrial fibrillation (Af) to define the optimal phase
      for ECG-gated image reconstruction for multi-slice CT (MSCT) of the left atrial
      appendage (LAA). We performed MSCT scans in 37 patients with Af, and we
      reconstructed multi-planar reformation images of the LAA, defined by the absolute
      delay (ms) immediately after the T wave, and by the relative delay (%). For
      visual analysis of the image quality for each image, a four-grade scoring system
      (poor to excellent) was used by two blinded, independent reviewers. Images
      obtained by absolute delay and by relative delay were classified as being of
      poor, fair, good, or excellent quality in 2, 2, 8, and 25 cases, and in 18, 11,
      8, and 0 cases, respectively. This phase-definition strategy in Af patients is
      more effective by absolute delay than by relative delay, and MSCT could provide
      an alternative diagnostic assessment of LAA thrombi.

PMID- 20821107
TI  - Nuclear collision processes around the Bragg peak in proton therapy.
AB  - In the physical processes of proton interaction in bio-materials, most of the
      proton energy is transferred to electrons. Ionization and excitation occur most
      frequently around the Bragg peak region, where nuclear reactions also exist. In
      this study, we investigated the processes of energy deposition by considering
      interactions including the nuclear reactions between protons and water molecules
      by a Monte Carlo simulation for proton therapy. We estimated the number of
      particles produced by a variety of nuclear reactions, and we focused on the
      interaction in the low-energy region (below 1 MeV). Furthermore, we considered
      the charge-changing processes in the low-energy region (less than a few hundred
      keV). Finally, we evaluated the total dose and the contribution of primary
      protons and secondary particles through nuclear reactions to the absorbed dose.
      The results showed that the protons generate numerous neutrons via nuclear
      reactions. Particularly, neutrons with relatively low energies produce recoil
      protons by elastic collisions with the hydrogen atoms. Around the Bragg peak, low
      energy primary protons (slowed-down protons) are prevalent, whereas recoil
      (secondary) protons gradually become dominant behind the distal falloff region of
      the Bragg peak. Therefore, around the Bragg peak, the main contribution to the
      absorbed dose is that of the primary protons (from 80 to 90%), whereas secondary
      protons created by primary proton-induced reactions contribute to the dose from
      20 to 5%. Behind the distal endpoint of the Bragg peak, the absorbed dose is
      mainly due to the protons produced by (1)H(n, p), and the contribution of these
      is about 70%.

PMID- 20821108
TI  - A statement of the rights of scientists and engineers. Editorial.

PMID- 20821109
TI  - Evaluation of errors influencing accuracy in image-guided neurosurgery.
AB  - Neurosurgeons sometimes find it difficult to locate tumors precisely during
      microsurgery, particularly tumors located in the brain parenchyma because of the
      absence of boundaries in this region. Image-guided neurosurgical techniques
      conducted with the help of neuronavigation systems have been developed and have
      gained importance recently. Accuracy is vital during image-guided neurosurgery.
      We used a phantom to evaluate the errors introduced during navigation. The three
      errors evaluated were skin-shift, marker-gap, and table-rotation errors. The skin
      shift error occurs if the fiducial markers positioned on the scalp move when the
      head is fixed to a head holder with head pins. The marker-gap error occurs when
      the marker ball is positioned incorrectly in the marker socket. The table
      rotation error occurs when the operating table is rotated for obtaining an
      intraoperative MR image and then returned to its original position. Our results
      indicated that skin shift decreased the navigation accuracy by an error of more
      than 4 mm, and the gap between the marker ball and the socket resulted in a
      decrease in navigation accuracy by an error of more than 5 mm. The table-rotation
      error was found to be negligible. The errors can be avoided by ensuring that the
      fiducial markers are positioned appropriately on the scalp and the marker ball is
      fitted well in the marker socket. A phantom is useful for evaluating accuracy,
      particularly for evaluating errors intrinsic to different operating rooms.
      Periodic quality assurance by use of a phantom in each operating room might aid
      in maintaining the accuracy of neuronavigation.

PMID- 20821110
TI  - Nationwide survey on the operational status of medical compact cyclotrons in
      Japan.
AB  - The management of induced radioactivity of the cyclotron itself and structures is
      an important issue in decommissioning of medical compact cyclotrons. To obtain
      basic data on the actual operational conditions of cyclotrons, we performed
      nationwide survey. The actual beam current was about half of the maximum beam
      current indicated in the official permits for cyclotron operation. The actual
      operating time was about 10% of the maximum operating time indicated in the
      official permits. The average daily radioactive-nuclide ((18)F) production was
      only 10% of the allowed maximum quantity. From these results, it became clear
      that the induced radioactivity of a cyclotron and its concrete structures based
      on the maximum beam current and the maximum operating time may be overestimated.
      These basic data are expected to be useful for a realistic evaluation and helpful
      in establishing a rational regulation in regard to radioactive waste control for
      decommissioning of medical cyclotrons.

PMID- 20821111
TI  - Bulk motion-independent analyses of water diffusion changes in the brain during
      the cardiac cycle.
AB  - We evaluated dynamic changes in water diffusion in the brain during the cardiac
      cycle by using cine diffusion MRI. On a 1.5-T MRI, ECG-triggered single-shot
      diffusion echo planar imaging was used with sensitivity encoding, halfscan, and
      rectangular field of view techniques for minimizing bulk motion effects such as
      brain pulsation, with a data-sampling window of 3 ms. The apparent diffusion
      coefficient (ADC) and fractional anisotropy (FA) in the white matter zone were
      determined in ten healthy volunteers and then compared with the intracranial
      volume change (ICVC) revealed by phase-contrast cine MRI during the cardiac
      cycle. In addition, a frequency analysis of these waveforms was performed. ADC
      and FA values changed significantly during the cardiac cycle, despite minimizing
      the effect of bulk motion, i.e., independent of bulk motion. The ADC was
      synchronized with the ICVC during the cardiac cycle. A significant positive
      correlation was noted among their amplitudes. Analysis of the dynamic change of
      water diffusion by use of cine diffusion MRI facilitates the assessment of
      intracranial conditions.

PMID- 20821112
TI  - Investigation of scatter fractions for estimating leakage dose in medical X-ray
      imaging facilities.
AB  - It is essential to make accurate estimates of the scatter of radiation from the
      human body when calculating the leakage dose in medical X-ray imaging facilities.
      The scatter fraction varies with the size and shape of the radiation field in a
      way that is not exactly proportional to the area of the field. Japanese law
      quotes values for the scatter fraction that are provided by the National Council
      on Radiation Protection and Measurements, but these data were obtained 30 years
      ago, using equipment that differed considerably from that employed nowadays. To
      date, no attempt has been made to confirm whether these data accurately describe
      current Japanese equipment. In the present study, we used an ion chamber
      dosimeter to measure scattered radiation fractions, and new scatter factor data
      are presented that resolve these problems.

PMID- 20821113
TI  - A statistical clustering approach to visualizing the relationship between early
      and delayed images in whole-body FDG-PET.
AB  - We propose a new method for diagnostic assistance in oncology, [fluorine-18]-2
      fluoro-2-deoxy-D: -glucose (FDG)-positron emission tomography (PET). Early and
      delayed scans were performed on 10 patients with lung cancer by use of an ECAT
      EXACT 47 PET scanner, and standardized-uptake-value (SUV) images were created.
      Three segmentation (S1, S2, and S3) maps were created from the early and delayed
      SUV images according to various thresholds (SUV(threshold) = 2.0, 2.5, and 3.0)
      based on the early image and the percentage change defined as (SUV(delayed) -
      SUV(early)) x 100/SUV(early). Voxels that had larger voxel values in their early
      images than the SUV(threshold) were clustered into three classes: S1 if the
      percentage change was larger than 10, S2 if the percentage change was between 0
      and 10, and S3 if the percentage change was negative. The S1 segments showed
      malignant lesions clearly; however, the S2 segments showed an SUV that had
      decreased from the S1 areas due to the partial volume effect or misalignment
      between the early and delayed scans. The S3 areas showed benignity or physiologic
      accumulation. The segmented images, S1, S2, and S3, were useful for clinical
      diagnosis with dual-phase FDG-PET scans and offer an easy way of exploring the
      longitudinal alteration in the SUV.

PMID- 20821114
TI  - Effect of daily setup errors on individual dose distribution in conventional
      radiotherapy: an initial study.
AB  - Recent linear accelerators can perform cone-beam computed tomography to correct
      setup errors immediately before dose delivery. We calculated the dose
      distribution with setup errors acquired from cone-beam computed tomography to
      determine a more realistic and individual effect of setup errors. The differences
      in dose distribution were analyzed. The setup errors of three patients who were
      irradiated in the neck, esophagus, and pelvic area were obtained retrospectively.
      We found that the maximum dose variances for the three cases were 19.9-35.9%. The
      maximum dose variance points were relatively far from the isocenter. The volume
      of the 10% dose difference had widths of 1.3-1.85 cm around the beam edges. The
      V95 and mean doses at the clinical target volume were mostly unchanged. Doses
      around the beam edges were more varied than those around the isocenter for every
      case. The dose on the spinal cord located near the beam edges varied by 5-10%
      compared with the dose of the radiotherapy plan in two of the cases. We
      demonstrated the individual dose distributions of the cases affected by daily
      setup errors for all fractions.

PMID- 20821115
TI  - Measurement of thermal neutron fluence distribution with use of 23Na
      radioactivation around a medical compact cyclotron.
AB  - A medical compact cyclotron produces about 10(15) neutrons per day along with 100
      GBq of (18)F. Therefore, it is important to establish radiation safety guidelines
      on residual radioactivity for routine operation, maintenance work, and
      decommissioning. Thus, we developed a simple method for measuring the thermal
      neutrons in a cyclotron room. In order to verify the feasibility of our proposed
      method, we measured the thermal neutron distribution around a cyclotron by using
      the activation of (23)Na in salt. We installed 78 salt dosimeters in the
      cyclotron room with a 50 cm mesh. The photopeak of (24)Na was measured, and the
      neutron flux distribution was estimated. Monitoring the neutron flux distribution
      in a cyclotron room appears to be useful for not only obtaining an accurate
      estimate of the distribution of induced radioactivity, but also optimizing the
      shield design for radiation safety in preparation for the decommissioning
      process.

PMID- 20821116
TI  - Comparison of viewing angle and observer performances in different types of
      liquid-crystal display monitors.
AB  - It is known that the performance of liquid-crystal display (LCD) monitors, such
      as the luminance and contrast ratio, is dependent on the viewing angle. Our
      purpose in this study was to compare the angular performance and the effect on
      observer performance of different types of LCD monitors. The luminance
      performance and contrast ratio as a function of viewing angle (-60 degrees to 60
      degrees) in each direction for two types of LCD monitors, namely, a general
      purpose LCD monitor and one especially designed for medical use, were measured in
      this study. Furthermore, the observer performance at various viewing angles in
      the horizontal direction for a medical-grade LCD monitor was investigated by
      eight observers based on a contrast-detail diagram. The two types of LCD monitors
      showed notable variations in luminance and contrast ratio as a function of the
      viewing angle. Acceptable viewing angles in terms of the contrast ratio were much
      smaller in each direction than those for nominal viewing angles in the
      specifications provided by the manufacturers, and those for the medical-grade LCD
      monitor in the horizontal and vertical directions were broader than those of the
      general-purpose LCD monitor. There was no significant difference in observer
      performance between 0 degrees and 40 degrees. On the other hand, our results
      showed a statistically significant difference in observer performance between 0
      degrees and 60 degrees.

PMID- 20821117
TI  - Application of an artificial neural network to the computer-aided differentiation
      of focal liver disease in MR imaging.
AB  - The differentiation of focal liver lesions in magnetic resonance (MR) imaging is
      primarily based on the intensity and homogeneity of lesions with different
      imaging sequences. However, these imaging findings are falsely interpreted in
      some patients because of the complexities involved. Our aim is to establish a
      computer-aided diagnosis system named LiverANN for classifying the pathologies of
      focal liver lesions into five categories using the artificial neural network
      (ANN) technique. On each MR image, a region of interest (ROI) in the focal liver
      lesion was delineated by a radiologist. The intensity and homogeneity within the
      ROI were calculated automatically, producing numerical data that were analyzed by
      feeding them into the LiverANN as inputs. Outputs were the following five
      pathologic categories of hepatic disease: hepatic cyst, hepatocellular carcinoma,
      dysplasia in cirrhosis, cavernous hemangioma, and metastasis. Of the 320 MR
      images obtained from 80 patients (four images per patient) with liver lesions,
      our LiverANN classified 50 cases of a training set into five types of liver
      lesions with a training accuracy of 100% and 30 test cases with a testing
      accuracy of 93%. The experiment demonstrated that our LiverANN, which functions
      as a computer-aided differentiation tool, can provide radiologists with a second
      opinion during the radiologic diagnostic procedure.

PMID- 20821118
TI  - Investigation on the optimal position for the quantification of hepatic perfusion
      by use of dynamic contrast-enhanced computed tomography in rats.
AB  - Our purpose in this study was to investigate the optimal position for the
      quantification of hepatic perfusion by using a dual-input, single-compartment
      model and dynamic contrast-enhanced computed tomography (DCE-CT) in rats. The DCE
      CT studies were performed with the animals in the supine and prone position, with
      an interval of 1 day, on six male Sprague-Dawley rats. The distance between the
      inferior vena cava (IVC) and portal vein was calculated. The arterial hepatic
      blood flow (AHBF) and portal hepatic blood flow (PHBF) were also estimated by use
      of time-density curves (TDCs) in the aorta, portal vein, and liver. The distance
      between the IVC and portal vein in the supine position (3.68 +/- 0.22 mm) was
      significantly greater than that in the prone position (2.56 +/- 0.19 mm). The
      estimated AHBF (102.1 +/- 8.9 ml/100 ml/min) and PHBF values (114.8 +/- 19.7
      ml/100 ml/min) in the prone position were significantly overestimated and
      underestimated, respectively, as compared to those in the supine position (76.1
      +/- 4.2 ml/100 ml/min for AHBF and 235.1 +/- 17.3 ml/100 ml/min for PHBF). We
      concluded that the supine position was more appropriate than the prone position
      for the quantification of hepatic perfusion by use of a dual-input, single
      compartment model and DCE-CT in rats, because the TDC in the portal vein is
      affected less by the TDC in the IVC in the supine position than in the prone
      position.

PMID- 20821119
TI  - Feasibility study of near-infrared fluorescence tomography using a positron
      emission tomograph equipped with depth-of-interaction PET detectors.
AB  - We are currently developing an imaging system that combines simultaneous positron
      emission tomography (PET) with near-infrared (NIR) optical tomography, thus
      supporting two different types of molecular imaging. For this system, we are
      considering whether to use depth of interaction (DOI) PET detectors as
      simultaneous detectors of gamma rays and NIR light by changing the original upper
      reflectors to dichroic mirrors. The DOI-PET detector has very low spatial
      resolution for NIR light compared to the charge-coupled device cameras that are
      normally used. However, it is possible to reconstruct images of comparable value
      from the data acquired by low-resolution devices because the light is scattered
      by biological tissues and high-resolution devices are not necessarily effective
      at improving image quality. In this study, we demonstrate the feasibility of 3D
      NIR fluorescence tomography imaging by employing DOI-PET detectors in computer
      simulations. In the simulations, we used a 40 mm x 40 mm x 40 mm cubic phantom, a
      square detector geometry, and an optical diffusion equation to approximate the
      light propagation. We then evaluated imaging systems for 3D fluorescence
      tomography with different detector resolutions and excitation light arrangements
      using singular-value analysis and imaging simulation. We confirmed that the
      reconstructed images from low-resolution detectors (8 x 8 pixels for an area of
      40 mm x 40 mm) are the same as those from high-resolution detectors (16 x 16
      pixels for the same area).

PMID- 20821120
TI  - An EGSnrc investigation of the air-kerma strength, dose rate constant, and radial
      dose function of 125I brachytherapy sources.
AB  - Titanium-encapsulated (125)I brachytherapy sources are in use for treatment of
      the eye, brain, and head and neck region, and for early stage prostate cancer.
      The photoelectric interaction of (125)I photons with titanium encapsulation
      generates Ti K X-rays (approximately 5 keV). According to the National Institute
      of Standards and Technology (NIST) 1999 air-kerma strength, S(k), standard, these
      X-rays should be excluded from S (k). We used the EGSnrc Monte Carlo code system
      to calculate the S(k) (including the contribution of approximately 5-keV X-rays),
      dose rate constant, and radial dose function for five different (125)I source
      models. Depending upon the source model, the contribution of 5-keV Ti X-rays to
      S(k) varies between 17.1 and 18.7%. Including these X-rays as part of S(k) would
      result in underestimation of the dose rate constant by up to 19%. The radial dose
      functions of the investigated sources are comparable to published studies that
      are based on an updated photon cross-section dataset.

PMID- 20821121
TI  - Study of intra-abdominal fat distribution in sigmoid colon cancer in Japanese
      patients by use of MDCT data.
AB  - To assess the relationship between intra-abdominal fat and sigmoid colon cancer,
      we investigated the intra-abdominal fat distribution in 172 examples of sigmoid
      colon cancer and 767 examples of various other pathologies by using data from
      multidetector-row computed tomography. One significant finding was that the intra
      abdominal fat area in sigmoid colon cancer presents a small secondary peak in the
      pelvis on the profile of the intra-abdominal fat, which we called the pelvic sub
      peak. The presence or absence of the pelvic sub-peak was determined based on the
      sub-peak ratio, which was calculated by dividing the maximum peak by the sub-peak
      value on the profile of the intra-abdominal fat area. The pelvic sub-peak was
      defined as having a sub-peak ratio >or=0.1. The pelvic sub-peak frequency was
      higher for all male patients than for female patients. The frequency of the
      pelvic sub-peak in sigmoid colon cancer was 77.5% (79/102) for men and 50.0%
      (35/70) for women. Among both men and women, frequencies of the pelvic sub-peak
      were significantly higher in patients with sigmoid colon cancer than in non-tumor
      cases (P < 0.001). Furthermore, the frequency of the pelvic sub-peak was almost
      the same in sigmoid colon cancer as in rectal cancer. No causal relationship
      between sigmoid colon cancer and a pelvic sub-peak could be confirmed in the
      present study; however, patients with sigmoid colon cancer tended to exhibit a
      unique pattern of fat accumulation.

PMID- 20821122
TI  - Monte Carlo simulations of electron beams collimated with a dual electron
      multileaf collimator: a feasibility study.
AB  - Electron applicators and cut-outs have been used for some time in the delivery of
      electron beam therapy. A dual electron multileaf collimator (eMLC) consisting of
      upper and lower eMLCs was designed, and dose distributions of electron beams
      delivered by it were evaluated by Monte Carlo simulations by use of the EGSnrc
      Monte Carlo code. The percentage depth dose (PDD), dose profiles, dose gradient
      falloff (G), depth of maximum dose (R(100)), surface dose, bremsstrahlung
      background, beam flatness, and penumbra of the dual eMLC were evaluated and
      compared with those simulated and measured with the standard applicators inserted
      into the treatment head of the medical linear accelerator (linac). The results
      showed good agreement in most cases. Specifically, the flatness and penumbra
      obtained with the dual eMLC were better than those obtained with standard
      applicators. It is therefore possible to use the proposed dual eMLC in the
      delivery of electron beam therapy without the need for applicators and cut-outs.
      This will minimize the inconvenience of placing cut-outs on the patients; also,
      changes in the required field can be effected without the therapist going into
      the accelerator room when the dual eMLC is finally automated. The absence of a
      helium bag between the upper and lower eMLCs did not offer significant changes in
      the dosimetry parameters compared to the eMLC fitted with the helium bag.

PMID- 20821123
TI  - A review of image-guided radiotherapy.
AB  - Image-guided radiotherapy (IGRT) is in the midst of a strong development and
      implementation cycle, stimulated by pioneering work performed in Japan. We
      present a review of the rationale, technology, and methodology of image guidance,
      as well as an overview of current work in IGRT at the Massachusetts General
      Hospital. The technology is rapidly evolving, and synergisms between the various
      acquisition approaches are converging to provide unparalleled information on
      target and normal tissue location and motion. With these new approaches to
      patient localization, we expect improved clinical results to be forthcoming.

PMID- 20821124
TI  - Use of a clinical MRI scanner for preclinical research on rats.
AB  - This study evaluated the feasibility of imaging rat brains using a human whole
      body 3-T magnetic resonance imaging (MRI) scanner with specially developed
      transmit-and-receive radiofrequency coils. The T(1)- and T(2)-weighted images
      obtained showed reasonable contrast. Acquired contrast-free time-of-flight
      magnetic resonance angiography images clearly showed the cortical middle cerebral
      artery (MCA) branches, and interhemispheric differences could be observed.
      Dynamic susceptibility contrast MRI at 1.17 mm(3) voxel resolution, performed
      three times following administration of gadolinium diethylenetriamine pentaacetic
      acid (Gd-DTPA, 0.1 mmol/kg), demonstrated that the arterial input function (AIF)
      can be obtained from the MCA region, yielding cerebral blood flow (CBF), cerebral
      blood volume, and mean transit time (MTT) maps. The hypothalamus (HT) to parietal
      cortex (Pt) CBF ratio was 45.11 +/- 2.85%, and the MTT was 1.29 +/- 0.40 s in the
      Pt region and 2.32 +/- 0.17 s in the HT region. A single dose of Gd-DTPA enabled
      the assessment of AIF within MCA territory and of quantitative CBF in rats.

PMID- 20821125
TI  - Deriving the modulation transfer function of CT from extremely noisy edge
      profiles.
AB  - The point spread function (PSF) method is currently the one predominantly used to
      determine the modulation transfer function (MTF) of an X-ray CT system. However,
      the image examined with the PSF method must have a very high contrast-to-noise
      ratio (CNR); it must also be reconstructed with a fine pixel pitch using a
      zooming reconstruction. Therefore, the PSF method is often inappropriate for
      describing the MTF of clinical operating conditions when image linearity is not
      guaranteed. The edge spread function (ESF) method requires no zooming
      reconstruction, but its susceptibility to image noise is no better than that of
      the PSF method. We describe a technique for rendering the ESF method robust to
      image noise. We smooth out the noisy ESF through multiple stages of filtering.
      Invariably, the line spread function (LSF) obtained from the smoothed ESF is
      blurred, and the MTF obtained from the LSF is incorrect. However, because the
      filtering that has been applied is known, much of the LSF blurring can be
      corrected. An estimate of the true LSF is obtainable from the blurred LSF,
      assuming that the true LSF is not very different from either a Gaussian or a
      composite of multiple Gaussians. For an image reconstructed with a kernel for
      soft-tissue imaging, the MTF obtained by our method is sufficiently consistent
      with the theoretical MTF, even when the CNR is as low as 2.

PMID- 20821126
TI  - Numerical evaluation of the effectiveness of colloidal gold as a contrast agent.
AB  - Monte Carlo numerical simulations were conducted to evaluate the effectiveness of
      colloidal gold as a contrast agent. The simulations were conducted using a simple
      configuration, modeling a phantom to maintain the generality of the results, and
      the effects of the mass percentage of gold accumulated inside the tumor and the
      energy of the irradiating X-rays were evaluated, as well as other information,
      such as the energy spectrum of the photons reaching the detector and the change
      in the energy deposited inside the phantom. The contrast of the X-ray image due
      to the layer is calculated from the total energy of photons transmitted to the
      back surface of the phantom. The simulation revealed that colloidal gold with a
      mass percentage of 1.0% provided an image for which the contrast was almost 70%
      of that for bone of the same thickness when X-rays from conventional X-ray tubes
      were considered. Monochromatic X-rays of 44, 66, and 88 keV, which simulated the
      Compton scattering monochromatic X-ray source being developed, were also
      evaluated. X-rays at the first two energies did not have a significant advantage
      over the rays from the X-ray tubes. For colloidal gold with a mass percentage of
      1.0%, the 88 keV monochromatic X-ray produced an image contrast that was about
      10% higher than the contrast for bone of the same thickness, as suggested by the
      K-absorption energy of gold. However, the improvement was not large considering
      the difficulty involved in making such a high-energy monochromatic X-ray source
      available.

PMID- 20821127
TI  - Development of a GPU-based multithreaded software application to calculate
      digitally reconstructed radiographs for radiotherapy.
AB  - To provide faster calculation of digitally reconstructed radiographs (DRRs) in
      patient-positioning verification, we developed and evaluated a graphic processing
      unit (GPU)-based DRR software application and compared it with a central
      processing unit (CPU)-based application. The evaluation metrics were calculation
      speed and image quality for various slice thicknesses. The results showed that
      the GPU-based DRR computation was an average of 50 times faster than the CPU
      based methodology, whereas the image quality was very similar. This excellent
      performance may increase the accuracy of patient positioning and improve the
      patient treatment throughput time.

PMID- 20821128
TI  - X-ray fluorescence camera for imaging of iodine media in vivo.
AB  - X-ray fluorescence (XRF) analysis is useful for measuring density distributions
      of contrast media in vivo. An XRF camera was developed for carrying out mapping
      for iodine-based contrast media used in medical angiography. Objects are exposed
      by an X-ray beam from a cerium target. Cerium K-series X-rays are absorbed
      effectively by iodine media in objects, and iodine fluorescence is produced from
      the objects. Next, iodine Kalpha fluorescence is selected out by use of a 58
      microm-thick stannum filter and is detected by a cadmium telluride (CdTe)
      detector. The Kalpha rays are discriminated out by a multichannel analyzer, and
      the number of photons is counted by a counter card. The objects are moved and
      scanned by an x-y stage in conjunction with a two-stage controller, and X-ray
      images obtained by iodine mapping are shown on a personal computer monitor. The
      scan pitch of the x and y axes was 2.5 mm, and the photon counting time per
      mapping point was 2.0 s. We carried out iodine mapping of non-living animals
      (phantoms), and iodine Kalpha fluorescence was produced from weakly remaining
      iodine elements in a rabbit skin cancer.

PMID- 20821129
TI  - Differentiation of hepatic tumors by use of image contrast with T2-weighted MRI.
AB  - Differentiation of hepatic tumors is often evaluated in terms of qualitative
      diagnostic performance. The signal intensity patterns of hepatic masses are known
      to differ on certain T2-weighted imaging sequences. In this study, we
      investigated the quantitative analysis of hepatic masses by using an index called
      the "T2-shine ratio." Fast-spin-echo (FSE), half-Fourier acquisition single-shot
      turbo spin echo (HASTE), and true-FISP sequences obtained with quick-imaging
      techniques during a single breath-hold were examined in 74 patients. T2-shine
      ratios were calculated by use of the signals of regions of interest (ROIs) placed
      on a tumor and peripheral tissue: the T2-shine ratio is defined as (tumor signal
      liver signal)/liver signal. The rate of change in the T2-shine ratio was compared
      among three sequences of FSE, HASTE, and true-FISP. The T2-shine ratio of FSE
      deducted from HASTE was significantly higher for hepatic cysts than for other
      masses. The T2-shine ratio of HASTE deducted from True-FISP was less than zero
      for hemangioma. For the value that deducted the T2-shine ratio of HASTE from the
      T2-shine ratio of true-FISP, hemangiomas had a significantly lower value than did
      cysts and metastases (P < 0.05), but there was no significant difference from
      hepatocellular carcinomas (HCCs). Although liver cysts, cavernous hemangiomas,
      and other lesions could be differentiated, it was virtually impossible to
      distinguish HCCs from metastatic tumors. In conclusion, the quantitative analysis
      of hepatic tumors was able to differentiate among these lesions by use of the T2
      shine ratio.

PMID- 20821130
TI  - Evaluating the performance of a MOSFET dosimeter at diagnostic X-ray energies for
      interventional radiology.
AB  - For reducing the risk of skin injury during interventional radiology (IR)
      procedures, it has been suggested that physicians track patients' exposure doses.
      The metal-oxide semiconductor field effect transistor (MOSFET) dosimeter is
      designed to measure patient exposure dose during radiotherapy applications at
      megavoltage photon energies. Our purpose in this study was to evaluate the
      feasibility of using a MOSFET dosimeter (OneDose system) to measure patients'
      skin dose during exposure to diagnostic X-ray energies used in IR. The response
      of the OneDose system was almost constant at diagnostic X-ray energies, although
      the sensitivity was higher than that at megavoltage photon energies. We found
      that the angular dependence was minimal at diagnostic X-ray energies. The OneDose
      is almost invisible on X-ray images at diagnostic energies. Furthermore, the
      OneDose is easy to handle. The OneDose sensor performs well at diagnostic X-ray
      energies, although real-time measurements are not feasible. Thus, the OneDose
      system may prove useful in measuring patient exposure dose during IR.

PMID- 20821131
TI  - Imaging simulations of an "OpenPET" geometry with shifting detector rings.
AB  - We have proposed a new "OpenPET" geometry consisting of two detector rings of
      axial length W each separated by a gap G. For obtaining an axially continuous
      field of view (FOV) of 2W + G, the maximum limit for G must be W. However, two
      valleys of sensitivity appear on both sides of the gap. Setting a more limited
      range for the gap as G < W, which is desirable for filling in the sensitivity
      valleys, results in not only a shortened gap, but also a shortened axial FOV. In
      this paper, we propose an alternative method for improving the uniformity of
      sensitivity by shifting two detector rings axially closer or further apart at the
      same velocity to each other. In addition, image reconstruction of the OpenPET is
      an incomplete problem, and low-frequency components are missing in the gap.
      Therefore, the proposed method is also expected to improve the conditions for the
      inverse problem. We simulated an OpenPET scanner which measures events
      simultaneously by shifting the detector rings. The results showed that the right
      and left peaks of the sensitivity approach each other upon shifting of the
      detector rings, and these valleys of sensitivity are effectively recovered. The
      results also showed that distortion, which is observed for objects containing low
      frequency components, is reduced. Larger detector shifts allow a more uniform
      axial distribution of sensitivity and a higher image quality, but at the cost of
      a smaller minimum gap. Therefore, an appropriate detector-shifting pattern should
      be determined based on the desired scanner application.

PMID- 20821133
TI  - Embossed radiography utilizing energy subtraction.
AB  - Currently, it is difficult to carry out refraction-contrast radiography by using
      a conventional X-ray generator. Thus, we developed an embossed radiography system
      utilizing dual-energy subtraction for decreasing the absorption contrast in
      unnecessary regions, and the contrast resolution of a target region was increased
      by use of image-shifting subtraction and a linear-contrast system in a flat panel
      detector (FPD). The X-ray generator had a 100-microm-focus tube. Energy
      subtraction was performed at tube voltages of 45 and 65 kV, a tube current of
      0.50 mA, and an X-ray exposure time of 5.0 s. A 1.0-mm-thick aluminum filter was
      used for absorbing low-photon-energy bremsstrahlung X-rays. Embossed radiography
      was achieved with cohesion imaging by use of the FPD with pixel sizes of 48 x 48
      microm, and the shifting dimension of an object in the horizontal direction
      ranged from 100 to 200 microm. At a shifting distance of 100 mum, the spatial
      resolutions in the horizontal and vertical directions measured with a lead test
      chart were both 83 microm. In embossed radiography of non-living animals, we
      obtained high-contrast embossed images of fine bones, gadolinium oxide particles
      in the kidney, and coronary arteries approximately 100 microm in diameter.

PMID- 20821132
TI  - New protocol of myocardial SPECT imaging with technetium-99m sestamibi for
      reducing the time interval between rest and adenosine stress phases.
AB  - We have developed a new protocol of myocardial perfusion-gated single-photon
      emission computed tomography (SPECT), by use of technetium-99m sestamibi (MIBI),
      in which SPECT imaging at rest followed by SPECT imaging after adenosine with low
      level ergometer stress can be conducted by use of the Monzen position within a
      shortened total testing time of 1 h or less. The study group consisted of 137
      patients who underwent this new imaging protocol. The diagnostic quality of the
      images was as good as that of images obtained with the conventional method (30-60
      min after the injection of MIBI). The SPECT image quality for the 137 patients
      was evaluated, and the percentages of images rated as excellent, good, fair, and
      poor were 65.3, 27.4, 5.8, and 1.5% for the rest image, and 68.2, 21.9, 8.4, and
      1.5% for the stress image, respectively. The shortened total testing time reduced
      the physical and mental burden on the patient compared with that of conventional
      myocardial perfusion imaging. Because this technique allows us to perform rest
      and stress myocardial imaging within a short period, it is expected to be very
      useful in the clinical setting.

PMID- 20821134
TI  - Dosimetric verification in inhomogeneous phantom geometries for the XiO
      radiotherapy treatment planning system with 6-MV photon beams.
AB  - We have developed a practical dose verification method for radiotherapy treatment
      planning systems by using only a Farmer ionization chamber in inhomogeneous
      phantoms. In particular, we compared experimental dose verifications of multi
      layer phantom geometries and laterally inhomogeneous phantom geometries for
      homogeneous and inhomogenous dose calculations by using the fast-Fourier
      transform convolution, fast-superposition, and superposition in the XiO
      radiotherapy treatment-planning system. We applied the dose verification method
      to three kernel-based algorithms in various phantom geometries with water-, lung-
      and bone-equivalent media of different field sizes. These calculations were then
      compared with experimental measurements by use of the Farmer ionization chamber.
      The fast-Fourier-transform convolution algorithm overestimated the dose by about
      8% in the lung phantom geometry. The superposition algorithm and the fast
      superposition algorithm were both accurate to better than 2% when compared to the
      measurements even for complex geometries. Our dose verification method was able
      to clarify the differences and equivalences of the three kernel-based algorithms
      and measurements with use only of commonly available apparatus. This will be
      generally useful in commissioning of inhomogeneity-correction algorithms in the
      clinical practice of treatment planning.

PMID- 20821135
TI  - Polarity effect in commercial ionization chambers used in photon beams with small
      fields.
AB  - Ionization chambers are the instruments of choice for use in photon dosimetry.
      Ionization chambers together with radiographic films represent the best detectors
      for measurement of dose distribution for a quality assurance (QA) program in
      intensity-modulated radiotheraphy (IMRT). The polarity effect was investigated
      for seven different commercially available ionization chambers. This study
      concentrated on measuring the dependence of the polarity effect at various
      energies, and for various field size, ionization chamber, and electrometer
      combinations. Of the seven chambers, CC01, PTW23323, and PTW31006 had the largest
      polarity effect for small field sizes. The materials of the central electrode of
      these three chambers were steel or air-equivalent plastic C-552. The magnitude of
      the polarity effect was shown to be strongly dependent on the material of the
      collecting electrode. This polarity effect dependence was observed for the
      ionization chambers and small field sizes studied.

PMID- 20821136
TI  - Need for liquid-crystal display monitors having the capability of rendering
      higher than 8 bits in display-bit depth.
AB  - Our purpose in this study was to examine the potential usefulness of liquid
      crystal display (LCD) monitors having the capability of rendering higher than 8
      bits in display-bit depth. An LCD monitor having the capability of rendering 8,
      10, and 12 bits was used. It was calibrated to the grayscale standard display
      function with a maximum luminance of 450 cd/m(2) and a minimum of 0.75 cd/m(2).
      For examining the grayscale resolution reported by ten observers, various simple
      test patterns having two different combinations of luminance in 8, 10, and 12
      bits were randomly displayed on the LCD monitor. These patterns were placed on
      different uniform background luminance levels, such as 0, 50, and 100%, for
      maximum luminance. All observers participating in this study distinguished a
      smaller difference in luminance than one gray level in 8 bits irrespective of
      background luminance levels. As a result of the adaptation processes of the human
      visual system, observers distinguished a smaller difference in luminance as the
      luminance level of the test pattern was closer to the background. The smallest
      difference in luminance that observers distinguished was four gray levels in 12
      bits, i.e., one gray level in 10 bits. Considering the results obtained by use of
      simple test patterns, medical images should ideally be displayed on LCD monitors
      having 10 bits or greater so that low-contrast objects with small differences in
      luminance can be detected and for providing a smooth gradation of grayscale.

PMID- 20821137
TI  - Water-equivalent pathlength reproducibility due to respiratory pattern variation
      in charged-particle pancreatic radiotherapy.
AB  - We evaluated the water-equivalent length (WEL) reproducibility due to variation
      in the external respiratory marker position when using a 4DCT scan in respiratory
      gated charged-particle treatment. Two sets of pancreatic 4DCT data from two
      patients were acquired under free breathing conditions with 256-slice CT. The
      4DCT data included two exhalation phases and the respiratory patterns in each
      patient differed, one being regular and the other irregular. The WEL calculation
      region is defined in the first respiratory cycle by two planes, one at the
      patient entrance surface and the other behind the target in the anterior
      posterior (AP) and posterior-anterior (PA) directions. In the regular respiratory
      pattern, the WEL variation within the target region was less than 1.7 mm between
      the first and second exhalations in both AP and PA calculation directions.
      However, in the irregular breathing pattern, the respiratory amplitude at the
      second exhalation was 20% lower than that at the first exhalation; therefore, WEL
      variations from 8.1 to -9.1 mm and from 3.1 to -3.4 mm were observed within the
      target region in the AP and PA calculation directions, respectively. The WEL
      variation in the PA direction was smaller than that in the AP direction because
      the abdominal thickness is affected more in the AP direction. Respiratory pattern
      variation even affects WEL values in the respiratory-gated phase. This variation
      should be considered in treatment planning, and necessary improvements in
      respiratory reproducibility should be made.

PMID- 20821138
TI  - Visualization of treatment response in tumors by use of dynamic contrast-enhanced
      magnetic resonance imaging.
AB  - Our goal in this study was to present a method for generating functional
      parametric maps of hemodynamic parameters in tumors and a visualization method
      for assessing treatment response by use of dynamic contrast-enhanced magnetic
      resonance imaging (DCE-MRI). A total of 13 patients with musculoskeletal tumors
      were included in this study. First, tumor blood flow (F(T)) maps were generated
      from DCE-MRI data by use of deconvolution analysis, and K(1), k(2), and f were
      obtained from a two-compartment model, where K(1) and k(2) denote the rate
      constant for the transfer of contrast agent from blood to tissue and from tissue
      to blood, respectively, and f is the fraction of the blood volume. Images were
      generated by application of the linear least squares method pixel by pixel.
      Furthermore, the images of the distribution volume (V(d)) and permeability
      surface area product (PS) were obtained from the relations V(d) = K(1)/k(2) and
      PS = -F(T) x ln(1 - K(1)/(F(T)), respectively. Second, two-dimensional (2D) plots
      were generated with V(d) and K(1) placed on the x- and y-axes, and three
      dimensional (3D) plots were generated by the addition of PS on the z-axis. In the
      case of good responders whose biopsied specimens revealed tumor necrosis greater
      than 90%, both 2D and 3D plots gradually approached the origin after an
      increasing number of treatments. On the other hand, in the case of non-responders
      whose biopsied specimens showed little chemotherapeutic effect, large changes
      were not observed in either plot. In conclusion, our method will be promising for
      evaluating the treatment response in tumors visually.

PMID- 20821139
TI  - Development of functional chest imaging with a dynamic flat-panel detector (FPD).
AB  - Dynamic FPD permits the acquisition of distortion-free radiographs with a large
      field of view and high image quality. In the present study, we investigated the
      feasibility of functional imaging for evaluating the pulmonary sequential blood
      distribution with an FPD, based on changes in pixel values during cardiac
      pumping. Dynamic chest radiographs of seven normal subjects were obtained in the
      expiratory phase by use of an FPD system. We measured the average pixel value in
      each region of interest that was located manually in the heart and lung areas.
      Subsequently, inter-frame differences and differences from a minimum-intensity
      projection image, which was created from one cardiac cycle, were calculated.
      These difference values were then superimposed on dynamic chest radiographs in
      the form of a color display, and sequential blood distribution images and a blood
      distribution map were created. The results were compared to typical data on
      normal cardiac physiology. The clinical effectiveness of our method was evaluated
      in a patient who had abnormal pulmonary blood flow. In normal cases, there was a
      strong correlation between the cardiac cycle and changes in pixel value.
      Sequential blood distribution images showed a normal pattern at determined by the
      physiology of pulmonary blood flow, with a symmetric distribution and no blood
      flow defects throughout the entire lung region. These findings indicated that
      pulmonary blood flow was reflected on dynamic chest radiographs. In an abnormal
      case, a defect in blood flow was shown as defective in color in a blood
      distribution map. The present method has the potential for evaluation of local
      blood flow as an optional application in general chest radiography.

PMID- 20821140
TI  - Sequential dual-energy subtraction technique with a dynamic flat-panel detector
      (FPD): primary study for image-guided radiation therapy (IGRT).
AB  - A sequential dual-energy subtraction technique for image-guided radiation therapy
      (IGRT) was developed. Here, we report on a computerized method for creating
      sequential soft-tissue images and the accuracy of tracking targets on the images
      obtained, in comparison to conventional fluoroscopic images. Two sets of
      sequential chest images during respiration of a normal subject were obtained with
      X-rays of different energy separately with a flat-panel detector (FPD).
      Sequential soft-tissue images were created from the two sets of sequential images
      consisting of real-time images and reference template images, respectively. The
      creation of sequential soft-tissue images consisted of three steps: one-to-one
      image correspondence of the two sequential images, image registration, and image
      subtraction in each frame. Motion tracking of lung vessels was then performed by
      the template-matching technique. For evaluation of the accuracy of motion
      tracking on the sequential soft-tissue images, the results were compared with
      those on the original sequential images. Sequential soft-tissue images provided
      more accurate tracking than the original images (P < 0.01). There was no
      significant error throughout all frames in the soft-tissue images, whereas the
      rib shadow introduced a tracking error in the original images. The maximum errors
      were 4.1 +/- 0.3 mm in the sequential soft-tissue images and 28.1 +/- 20.0 mm in
      the original images. In conclusion, sequential soft-tissue images were helpful
      for tracking of a target affected by respiratory motion. Dual-energy subtraction
      has the potential to improve the accuracy of IGRT without implanted markers.

PMID- 20821141
TI  - Radial-searching contour extraction method based on a modified active contour
      model for mammographic masses.
AB  - In this study, we developed an automatic extraction scheme for the precise
      recognition of the contours of masses on digital mammograms in order to improve a
      computer-aided diagnosis (CAD) system. We propose a radial-searching contour
      extraction method based on a modified active contour model (ACM). In this
      technique, after determining the central point of a mass by searching for the
      direction of the density gradient, we arranged an initial contour at the central
      point, and the movement of a control point was limited to directions radiating
      from the central point. Moreover, it became possible to increase the extraction
      accuracy by sorting out the pixel used for processing and using two images-an
      edge-intensity image and a degree-of-separation image defined based on the pixel
      value histogram-for calculation of the image forces used for constraints on
      deformation of the ACM. We investigated the accuracy of the automated extraction
      method by using 53 masses with several "difficult contours" on 53 digitized
      mammograms. The extraction results were compared quantitatively with the "correct
      segmentation" represented by an experienced physician's sketches. The numbers of
      cases in which the extracted region corresponded to the correct region with
      overlap ratios of more than 81 and 61% were 30 and 45, respectively. The initial
      results obtained with this technique show that it will be useful for the
      segmentation of masses in CAD schemes.

PMID- 20821142
TI  - Evaluation of the accuracy of CT numbers in statistical correction of
      nonlinearity for polychromatic X-ray CT projection data.
AB  - The CT number is theoretically independent of the number of incident photons and
      the thickness of a subject. However, when noise is added, the CT number becomes
      dependent on the number of incident photons because of the nonlinearity of the
      logarithm operation, and so the accuracy of the CT number is degraded, especially
      in a photon-starved state. The inconsistency of the CT number due to nonlinearity
      generates an intense streak artifact in a reconstructed image. We have
      theoretically clarified the statistical characteristics of both the nonlinearity
      of the logarithm transform and the non-zero/non-negative restriction in the
      logarithm operation. Moreover, we have formulated a correction method for such
      nonlinearity according to the statistical distribution of noise, and we carried
      out computer simulations for monochromatic X-ray beams. However, the
      applicability to polychromatic-energy photons has not been confirmed. The
      artifacts induced by the beam-hardening effect, which occurs when incident beams
      are polychromatic, remarkably deteriorate the accuracy of the CT number. In this
      paper, we quantitatively evaluate the improvement of the quality of reconstructed
      images by our correction method by using a numerical experiment when incident
      beams are polychromatic. The experimental results show that there is less
      influence on spatial resolution and that the CT number is hardly dependent on the
      number of incident photons for a polychromatic beam as well as a monochromatic
      beam. Moreover, the results suggest the possibility that the same image quality
      is obtained at a much lower exposure level than the clinical exposure level of
      low-dose CT.

PMID- 20821143
TI  - Dose verifications by use of liquid ionization chamber of an electronic portal
      imaging device (EPID).
AB  - In this study, we examined the ability of an L-EPID to verify rectangular and
      irregular fields and to measure the transmitted exit doses. With respect to the
      beam profile of rectangular and irregular fields and the doses transmitted
      through an inhomogeneous phantom, the L-EPID dose obtained from the L-EPID
      measurement was compared with the conventional dose measured by use of a 0.12-cc
      ionization chamber and a 3D water phantom. In the comparison of the rectangular
      and irregular fields, the difference in the off-center ratio (OCR) between the L
      EPID dose and the conventional dose was approximately 3% in the steep-dose
      gradient region (penumbra regions, >30%/cm) and approximately +/-0.5% in the
      gentle-dose-gradient region (5%/cm). On the other hand, the dose differences
      between the L-EPID and the measured doses were less than approximately 2% in the
      gentle-dose-gradient region. In addition, in the steep-dose-gradient region, the
      maximum difference was 30%. However, the differences in the distance-to-agreement
      (DTA) were less than approximately +/-1 mm and were unrelated to the dose
      gradient. These results suggest that dose verification by L-EPID is very useful
      in clinical applications.

PMID- 20821144
TI  - Analysis of respiration-related movement of upper abdominal arteries: preliminary
      measurement for the development of a respiratory motion compensation technique of
      roadmap navigation.
AB  - In this study, we analyzed the respiratory motion of the upper abdominal arteries
      preliminary to developing a method of respiratory motion correction for the
      roadmap technique used in vascular interventions. We retrospectively obtained six
      digital angiography sequences taken during respiration. The levels of the right
      and left hemidiaphragms and the positions of artery bifurcation points were
      measured manually through each sequence. Artery bifurcation points were
      classified as the hepatic artery group (HAG), splenic artery group (SAG), and
      celiac group (CG). Correlations between the motions of each hemidiaphragm and of
      the artery bifurcation points in each group were determined. We found that the
      vertical motion of the HAG and CG matched that of the right hemidiaphragm (r =
      0.924 and r = 0.888, respectively). The vertical motion of the SAG matched that
      of the left hemidiaphragm (r = 0.949). The mean horizontal movements for all
      groups were up to 1.90 mm. The vertical motion for each group matched that of the
      right or the left hemidiaphragm. These findings will facilitate the development
      of a method of respiratory motion correction for the roadmap technique.

PMID- 20821145
TI  - Dosimetric evaluation of nuclear interaction models in the Geant4 Monte Carlo
      simulation toolkit for carbon-ion radiotherapy.
AB  - We tested the ability of two separate nuclear reaction models, the binary cascade
      and JQMD (Jaeri version of Quantum Molecular Dynamics), to predict the dose
      distribution in carbon-ion radiotherapy. This was done by use of a realistic
      simulation of the experimental irradiation of a water target. Comparison with
      measurement shows that the binary cascade model does a good job reproducing the
      spread-out Bragg peak in depth-dose distributions in water irradiated with a 290
      MeV/u (per nucleon) beam. However, it significantly overestimates the peak dose
      for a 400 MeV/u beam. JQMD underestimates the overall dose because of a tendency
      to break a nucleus into lower-Z fragments than does the binary cascade model. As
      far as shape of the dose distribution is concerned, JQMD shows fairly good
      agreement with measurement for both beam energies of 290 and 400 MeV/u, which
      favors JQMD over the binary cascade model for the calculation of the relative
      dose distribution in treatment planning.

PMID- 20821146
TI  - Method for reducing noise in X-ray images by averaging pixels based on the
      normalized difference with the relevant pixel.
AB  - A real-time digital filter for noise reduction in X-ray images is proposed. The
      filter is based on averaging of only similar pixels (pixels that differ only
      little) rather than neighboring pixels, which are averaged in conventional linear
      low-pass filters. The effectiveness of the filter was evaluated by computer
      simulation, where original images that were acquired by X-ray exposure were
      processed in accordance with the filter algorithm. The resulting images were
      evaluated in terms of the pre-sampled modulation transfer function (MTF), the
      noise power spectrum (NPS), and the lag. Comparison of the filtered and original
      images revealed that the NPS was reduced for the full range of spatial
      frequencies in the filtered image, resulting in a reduction of total noise power
      to about 1/9 the level in the original image with no degradation in the MTF or
      lag. The usefulness of the filter was demonstrated in fluoroscopic, digital
      subtraction angiography (DSA) and mammographic phantom studies. The filter was
      found to have the potential to reduce the patient dose by reducing the noise in
      dynamic as well as static X-ray images.

PMID- 20821147
TI  - Customization of normal data base specific for 3-tesla MRI is mandatory in VSRAD
      analysis.
AB  - A voxel-based specific regional analysis system for Alzheimer's disease (VSRAD)
      was used for quantitative analysis of parahippocampal atropy with 1.5-tesla (T)
      MRI in a voxel-wise manner. The analysis of images acquired under a different
      imaging condition provides an error factor that has a calculated value. Clinical
      application of 3T-MRI is necessary for establishing a normal data base (N-DB)
      specific for 3T-MRI data, which permits appropriate application of VSRAD. We
      established an N-DB specific for 3T-MRI for use in VSRAD. The "Z-score of the
      parahippocampal gyrus" was 0.79 +/- 0.32, and the N-DB of each age group did not
      have a big deflection when we analyzed a group of physically unimpaired persons
      in an N-DB specific for 3T-MRI. Therefore, we were able to confirm the validity
      of the customized N-DB. The "Z-score of the parahippocampal gyrus" was 1.62 +/-
      0.47 for the N-DB of VSRAD. The numerical value was high for the group of
      physically unimpaired persons.

PMID- 20821148
TI  - Analysis method of noise power spectrum for medical monochrome liquid crystal
      displays.
AB  - We investigated methods of analyzing the noise power spectrum (NPS) measurement
      for medical liquid crystal displays (LCDs). Uniform images displayed on the LCDs
      were imaged with a high-performance digital camera equipped with a close-up lens,
      and then the NPSs were calculated from the image data by means of several
      analysis methods. In a method using the 2D fast Fourier transform (FFT) with a
      256 x 256 pixels data segment (basic method), we examined the efficacy of a
      background trend correction (BTC) and a Hanning windowing process used for
      reducing the spectral estimation errors in the Fourier analysis. To improve the
      frequency resolution of the basic method, we examined two 2D FFT methods by using
      512 x 512 and 1024 x 1024 pixel segments. In addition, we studied a 1D FFT method
      with 1024-point 1D noise profiles (1D method). In these three methods, the BTC by
      a second-order polynomial fit and Hanning windowing were commonly applied. A 3
      mega-pixel (MP) and a 5-MP monochrome LCD were employed for evaluating the
      respective methods. Also, a prototype 5-MP LCD equipped with a new anti
      reflection surface-coated panel was compared with the conventional 5-MP LCD. The
      Hanning windowing process was indispensable for avoiding the spectral leakage
      errors caused by the pixel structures of the LCD. Sufficient frequency resolution
      was obtained by the 2D FFT method with the 1024 x 1024 pixels segments and the 1D
      method. The method which provided the most reliable NPSs was the 1D method, with
      which the BTC was achieved successfully.

PMID- 20821149
TI  - Optimal timing of MR sialography by use of a simple method of stimulating the
      salivary gland: a preliminary report.
AB  - The present study was performed for determining the optimal timing of MR
      sialography by use of the Japanese pickled plum (umeboshi) for promoting
      secretion by the salivary glands. MR sialography was performed in four healthy
      male volunteers. The four volunteers were examined before and 10 min after
      stimulation with umeboshi. On the next examination, three volunteers were
      examined before and after umeboshi stimulation every 1 min up to 5 min to allow
      assessment of the temporal changes in duct visualization. Dilatation of the
      salivary gland ducts and improvement of the visualization of the ducts were
      obtained after stimulation with umeboshi. The difference in the dilatation of the
      parotid duct was statistically significant. In the temporal study, the salivary
      gland ducts were shown to be dilated at 2 min after stimulation. As a result, 2
      min after stimulation is the optimal timing for MR sialography by use of umeboshi
      as a stimulator of salivary secretion.

PMID- 20821150
TI  - Automated segmentation of hepatic vessels in non-contrast X-ray CT images.
AB  - Hepatic-vessel trees are the key structures in the liver. Knowledge of the
      hepatic-vessel tree is required because it provides information for liver lesion
      detection in the computer-aided diagnosis (CAD) system. However, hepatic vessels
      cannot easily be distinguished from other liver tissues in plain CT images.
      Automated segmentation of hepatic vessels in plain (non-contrast) CT images is a
      challenging issue. In this paper, an approach to automatic segmentation of
      hepatic vessels is proposed. The approach consists of two processing steps:
      enhancement of hepatic vessels and hepatic-vessel extractions. Enhancement of the
      vessels was performed with two techniques: (1) histogram transformation based on
      a Gaussian function; (2) multi-scale line filtering based on eigenvalues of a
      Hessian matrix. After the enhancement of the vessels, candidates of hepatic
      vessels were extracted by a thresholding method. Small connected regions in the
      final results were considered as false positives and were removed. This approach
      was applied to 2 normal-liver cases for whom plain CT images were obtained.
      Hepatic vessels segmented from the contrast-enhanced CT images of the same
      patient were used as the ground truth in evaluation of the performance of the
      proposed approach. The index of separation ratio between the CT number
      distributions in hepatic vessels and other liver tissue regions was also used in
      the evaluation. A subjective evaluation of the hepatic-vessel extraction results
      based on the additional 16 plain CT cases was carried out for a further
      validation by a radiologist. The preliminary experimental results showed that the
      proposed method could enhance and segment the hepatic-vessel regions even in
      plain CT images.

PMID- 20821151
TI  - Comparison of dosimetric characteristics of 120-leaf and 80-leaf multi-leaf
      collimators in a Varian linear accelerator for a 6-MV photon beam.
AB  - In this study, the dosimetric characteristics of multileaf collimators (MLCs)
      with 120 leaves and 80 leaves were evaluated. The dose rate, percentage depth
      dose, surface dose, dose in the build-up region, beam profile, flatness,
      symmetry, and penumbra width were measured by three field-defining methods: (1)
      "Jaw only", (2) "MLC only", and (3) "MLC + Jaw", for a 6-MV photon beam with the
      two MLC systems. Analysis of the dose rate showed that the dose rate for the "MLC
      only" field was higher than that for the other two fields. The surface dose was
      more pronounced for the "MLC only" fields. The dose in the build-up region was
      higher for the "MLC only" fields, and no significant difference was found in the
      percentage depth dose (PDD) beyond the dose maximum point (d(max)) for both MLC
      systems. Beam profiles showed that the differences in flatness and symmetry for
      both systems were less than 3%. The penumbra width between 80 and 20% isodose
      levels for the "MLC only" field was more than that for the other two field
      defining methods. The widths of the 50% dose levels of the beam profiles were
      analyzed. The dosimetric characteristics of the two MLC systems were the same in
      all aspects except the surface dose, penumbra, the dose in the build-up region,
      and the width of the 50% dose levels.

PMID- 20821152
TI  - Evaluation of the spatial resolution of multiplanar reconstruction images.
AB  - We present a simple method for evaluating the spatial resolution of multi-slice
      computed tomography (MSCT) multiplanar reconstruction images (MPRs). We scanned a
      bead phantom to obtain the three-dimensional point spread function (PSF), and
      bead-centric MPRs were generated. The modulation transfer function (MTF) was
      calculated from the MPRs via a two-dimensional Fourier transform (2DFFT) of the
      PSF. The results showed that, when MPRs were reconstructed using axial images
      less than or equal to a nominal 1.0-mm slice-width with a standard kernel for the
      abdomen, the MTF in the longitudinal direction (z-direction) was superior to that
      in the in-plane (x-y plane) direction. It was also found that the arbitrary-angle
      MTFs of MPRs were between the MTFs of the in-plane and longitudinal directions.
      It was confirmed that this method can be used to evaluate MPR spatial resolution.

PMID- 20821153
TI  - Application of breath-holding SPECT with high-speed-rotation technique in hepatic
      function scintigraphy.
AB  - Recently, a new method for acquiring SPECT data in deep inspiratory breath hold
      with a high-speed rotation (HSR-SPECT) technique was developed for pulmonary
      perfusion scintigraphy. Our purpose in this study was to apply this method to
      hepatic-function scintigraphy. A phantom study was performed for determining data
      acquisition times. The coefficient of variation (CV) value was used for
      evaluating nonuniformity of radioactivity in the liver area. Data acquisition
      times were determined based on the CV value. According to the results of the
      phantom study, this method needs at least ten projection data sets for acquiring
      sufficient counts for a proper diagnosis. Under clinical conditions, breath
      holding HSR-SPECT can suppress the respiratory motion effects, better than the
      conventional method can. In addition, the fusion images made from breath-holding
      HSR-SPECT images match excellently with CT images.

PMID- 20821154
TI  - Evaluation of chest and abdominal exposure dose appropriate for a digital image
      reader system incorporating a columnar-crystal structured phosphor plate and a
      contrast-detail phantom.
AB  - We evaluated a newly developed digital image reader incorporating a columnar
      crystal structured phosphor plate (CPP) to determine its effectiveness for chest
      and abdominal exposures by assessing contrast-detail (C-D) curves and image
      quality figure values obtained from a C-D phantom. With the help of five
      radiologic technologists with 5 years or more of experience in the interpretation
      of plain radiographs, we assessed chest and abdominal radiographic films that had
      undergone image processing. The exposure dose required for obtaining the same
      image quality under chest exposure conditions (110 kV) was 66% of that necessary
      for a conventionally used computed radiography system incorporating a powder
      phosphor plate, whereas the percentage under abdominal exposure conditions (85
      kV) was 82%. The rate of dose reduction varied depending on the anatomic region
      radiographed, the exposure conditions applied, and the method of image processing
      employed. Because the CPP has a higher X-ray detection efficiency than the
      hitherto-used powder phosphor plate, its use has to potential to reduce the
      patients' radiation exposure dose.

PMID- 20821155
TI  - Low-dose CT screening for lung cancer with automatic exposure control: phantom
      study.
AB  - We conducted a study to determine optimal scan conditions for automatic exposure
      control (AEC) in computed tomography (CT) of low-dose chest screening in order to
      provide consistent image quality without increasing the collective dose. Using a
      chest CT phantom, we set CT-AEC scan conditions with a dose-reduction wedge (DR
      Wedge) to the same radiation dose as those for low-tube current, fixed-scan
      conditions. Image quality was evaluated with the use of the standard deviation of
      the CT number, contrast-noise ratios (CNR), and receiver-operating characteristic
      (ROC) analysis. At the same radiation dose, in the scan conditions using CT-AEC
      with the DR-Wedge, the SD of the CT number of each slice position was stable. The
      CNR values were higher at the lung apex and lung base under CT-AEC with the DR
      Wedge than under standard scan conditions (p < 0.0002). In addition, ROC analysis
      of blind evaluation by four radiologists and three technologists showed that the
      image quality was improved for the lung apex (p < 0.009), tracheal bifurcation (p
      < 0.038), and lung base (p < 0.022) in the scan conditions using CT-AEC with the
      DR-Wedge. We achieved improvement of image quality without increasing the
      collective dose by using CT-AEC with the DR-Wedge under low-dose scan conditions.

PMID- 20821156
TI  - Message from the Editor-in-Chief and Deputy Editors.

PMID- 20821158
TI  - Contrast resolution in multidetector-row CT with 16 detector rows: phantom study.
AB  - This study was performed for evaluation of high- and low-contrast resolution in
      multidetector-row CT (MDCT) with 16 detector rows. For evaluating high-contrast
      resolution, a phantom was scanned ten times at 100 mA s with 24 patterns of scan
      parameters under several X-ray beam widths, X-ray tube voltages, X-ray tube
      rotation times, and helical pitches. Three radiological technologists observed
      the images visually. For evaluating low-contrast resolution, a phantom was
      scanned ten times at 100 mA s with the 24 patterns of scan parameters, which were
      the same as for high-contrast resolution. The images were examined based on
      receiver operating characteristic (ROC) curves. The high-contrast resolution
      deteriorated in the off-center locations when helical pitches of 1.375:1 or
      1.75:1 were used. High helical pitch (>0.9375:1) and low tube voltage had
      significant effects on the low-contrast resolution. However, a wide X-ray beam
      width and short X-ray tube rotation time had no definite influence. Therefore, a
      helical pitch of 0.5625:1 should be used when the contrast resolutions are really
      important, and a wide X-ray beam width and short X-ray tube rotation time can
      improve the temporal resolution without deterioration of contrast resolution.

PMID- 20821157
TI  - ROC analysis in medical imaging: a tutorial review of the literature.
AB  - Receiver operating characteristic (ROC) analysis measures the "diagnostic
      accuracy" of a medical imaging system, which represents the second level of
      diagnostic efficacy in the hierarchical model described by Fryback and Thornbury
      (Med Decis Making 11:88-94, 1991). After describing the historical origins of ROC
      analysis, this paper reviews the importance of sampling cases appropriately,
      designing an observer study to avoid bias, and collecting data on a useful scale.
      A variety of methods for fitting ROC curves to observer data and testing the
      statistical significance of apparent differences are then reported. Finally,
      generalized forms of ROC analysis that require lesion localization or allow more
      than two states of truth are surveyed briefly.

PMID- 20821159
TI  - Development and performance evaluation of the second model 256-detector row CT.
AB  - Since our initial development of the 256-detector row CT scanner (256-row CT) for
      four-dimensional (4D) imaging of moving organs in 2003, the results of physical
      performance and those in animal and human studies have suggested that this
      scanner may be useful in the examination of moving organs such as the heart and
      lungs. We have now developed a second model of the 256-row CT with improved
      specifications, with a scan time of 0.5 s/rotation at the highest speed and real
      time reconstruction and display of dynamic 3D images (4D images). Here, we
      investigated the image characteristics of the new model, including spatial
      resolution, noise, and low-contrast detectability, as well as the dose profile
      and its integral in stationary phantoms. One volunteer and one patient with lung
      cancer were scanned, and their images were evaluated. The results show that all
      characteristics have been improved compared with those of the first model, with a
      remarkable improvement in the low-contrast detectability and slice sensitivity
      profile. In a contrast study, coronary arteries were clearly visualized in the
      normal heart without electrocardiographic gating. Movement and deformation of the
      tumor in the patient with lung cancer was captured in a study of a single breath
      cycle. The second model 256-row CT with improved characteristics may be
      beneficial in imaging of moving organs such as the heart and lungs, and may
      enable cerebral perfusion studies of the whole brain.

PMID- 20821160
TI  - Development of a cardiac evaluation method using a dynamic flat-panel detector
      (FPD) system: a feasibility study using a cardiac motion phantom.
AB  - The purpose of this study is to investigate the feasibility of cardiac evaluation
      with a dynamic flat-panel detector (FPD), based on changes in pixel values during
      cardiac pumping. To investigate the feasibility of cardiac evaluation with a
      dynamic flat-panel detector (FPD), based on changes in pixel values during
      cardiac pumping. Sequential radiographs of a cardiac motion phantom and water
      equivalent material step were obtained with an FPD system. Various combinations
      of cardiac output and heart rate were evaluated with and without contrast medium.
      The ventricular area and summation of pixel values in the ventricles were
      measured. The ejection fraction (EF) was calculated based on the rate of changes
      and then compared to EF obtained from computed tomography images. In addition,
      slight changes in pixel values were visualized by use of inter-frame subtraction
      and color-mapping. The result of a clinical case was examined according to
      cardiac physiology. There were strong correlations between EF and our results.
      There was no significant difference between the findings with and without
      contrast medium. When the heart rate was greater than 60 bpm, EF obtained with
      our method were underestimated. It is necessary for a patient to be examined at
      an imaging rate between 7.5 and 10 fps at least. In addition, a +/-1.2% change in
      pixel value was equivalent to a +/-10 mm change in the thickness of water. Color
      mapping images were supported by cardiac physiology. Evaluating changes in pixel
      values on dynamic chest radiography with FPD has the potential to demonstrate
      cardiac function without contrast medium. Inter-frame subtraction and color
      mapping are very useful for interpreting changes in pixel value as velocities of
      blood flow.

PMID- 20821162
TI  - Volumetric tracking tool using four-dimensional CT for image guided-radiation
      therapy.
AB  - To analyze lung vessel motion automatically, we developed computerized tracking
      software for multi-slice CT (MSCT) data. Here, we evaluated the tracking accuracy
      in images of healthy porcine lungs obtained by 256 multi-slice CT (256-MSCT). A
      domestic pig was scanned with 256-MSCT under free breathing conditions. The 256
      MSCT provides 128-mm scan coverage with a 0.5-mm slice thickness in a single
      rotation (1.0 s/rot). Automatic tracking was performed by template matching,
      where volumes of interest (VOIs) can be identified by mouse click on all three
      principal orthogonal planes (axial, sagittal and coronal). The results were
      compared with those obtained by manual tracking. There was no significant
      difference between the results obtained with the computerized method and those
      with the manual method. The maximum tracking error was less than 1.4 mm in all
      directions. The computerized method allowed real-time tracking and significantly
      saved time in determining target displacement. The present method, 256-MSCT with
      a computerized tracking system, could quantify hysteresis-like behavior of lung
      vessels during respiration in 4DCT data. The quantitative information on the
      target trajectory is expected to be useful for clinical radiotherapy planning and
      IGRT to the lower lobe of the lung and liver area, which show large respiratory
      displacement.

PMID- 20821161
TI  - Automatic tube current modulation technique for multidetector CT: is it effective
      with a 64-detector CT?
AB  - To investigate whether it is possible to obtain adequate images at uniform image
      noise levels and reduced radiation exposure with our automatic tube current
      modulation (ATCM) technique for 64-detector CT. The study population consisted of
      64 patients with known or suspected lung or abdominal disease. We used a 64
      detector CT scanner (LightSpeed VCT, GE Healthcare, Waukesha, WI, USA) and a
      combined angular and longitudinal tube current modulation technique (Smart mA, GE
      Healthcare, Waukesha, WI, USA) to examine 34 patients. The scanning parameters
      were identical; the minimum and maximum tube current thresholds were 50 and 800
      mA, respectively. For study of the constant tube current technique, 30 additional
      patients were examined at 350 mA. The CT number and image noise (SD of the CT
      number) were measured in the 64 patients at six levels, i.e., the center of the
      left ventricle, the liver dome, the porta hepatis, the center of the spleen and
      the right and left renal pelvis. When we used the ATCM technique, the mean image
      noise ranged from 8.40 at the center of the left ventricle to 11.31 at the porta
      hepatis; the mean tube current ranged from 105.9 mAs at the center of the left
      ventricle to 169.6 mAs at the center of the spleen. The mean dose reduction rate
      per constant tube current at 175 mAs ranged from 3.1 to 39.5%. By use of the ATCM
      technique, it is possible to maintain a constant image noise level with a 64
      detector CT.

PMID- 20821163
TI  - Experimental verification of proton beam monitoring in a human body by use of
      activity image of positron-emitting nuclei generated by nuclear fragmentation
      reaction.
AB  - Proton therapy is a form of radiotherapy that enables concentration of dose on a
      tumor by use of a scanned or modulated Bragg peak. Therefore, it is very
      important to evaluate the proton-irradiated volume accurately. The proton
      irradiated volume can be confirmed by detection of pair-annihilation gamma rays
      from positron-emitting nuclei generated by the nuclear fragmentation reaction of
      the incident protons on target nuclei using a PET apparatus. The activity of the
      positron-emitting nuclei generated in a patient was measured with a PET-CT
      apparatus after proton beam irradiation of the patient. Activity measurement was
      performed in patients with tumors of the brain, head and neck, liver, lungs, and
      sacrum. The 3-D PET image obtained on the CT image showed the visual
      correspondence with the irradiation area of the proton beam. Moreover, it was
      confirmed that there were differences in the strength of activity from the PET-CT
      images obtained at each irradiation site. The values of activity obtained from
      both measurement and calculation based on the reaction cross section were
      compared, and it was confirmed that the intensity and the distribution of the
      activity changed with the start time of the PET imaging after proton beam
      irradiation. The clinical use of this information about the positron-emitting
      nuclei will be important for promoting proton treatment with higher accuracy in
      the future.

PMID- 20821164
TI  - Dosimetric evaluation of a MOSFET detector for clinical application in photon
      therapy.
AB  - Dosimetric characteristics of a metal oxide-silicon semiconductor field effect
      transistor (MOSFET) detector are studied with megavoltage photon beams for
      patient dose verification. The major advantages of this detector are its size,
      which makes it a point dosimeter, and its ease of use. In order to use the MOSFET
      detector for dose verification of intensity-modulated radiation therapy (IMRT)
      and in-vivo dosimetry for radiation therapy, we need to evaluate the dosimetric
      properties of the MOSFET detector. Therefore, we investigated the
      reproducibility, dose-rate effect, accumulated-dose effect, angular dependence,
      and accuracy in tissue-maximum ratio measurements. Then, as it takes about 20 min
      in actual IMRT for the patient, we evaluated fading effect of MOSFET response.
      When the MOSFETs were read-out 20 min after irradiation, we observed a fading
      effect of 0.9% with 0.9% standard error of the mean. Further, we applied the
      MOSFET to the measurement of small field total scatter factor. The MOSFET for
      dose measurements of small field sizes was better than the reference pinpoint
      chamber with vertical direction. In conclusion, we assessed the accuracy,
      reliability, and usefulness of the MOSFET detector in clinical applications such
      as pinpoint absolute dosimetry for small fields.

PMID- 20821165
TI  - Realization of reliable cerebral-blood-flow maps from low-dose CT perfusion
      images by statistical noise reduction using nonlinear diffusion filtering.
AB  - X-ray computed tomographic perfusion (CTP) imaging, a rapid method for measuring
      cerebral blood flow (CBF), is an effective modality for assessment of the
      severity and extent of brain tissue ischemia. Low-dose scanning has been required
      for CTP imaging for reducing the radiation exposure to patients, because the same
      plane is scanned repeatedly. Low-dose CTP imaging, however, results in
      substantial statistical noise in the images, which may negatively impact the
      accuracy of CBF values. Because CBF values are calculated from the set of CTP
      images, it is important to reduce the statistical noise in raw CTP images to make
      the values reliable. Noise reduction must be performed without blurring of vessel
      structures, because such blurring will overestimate CBF values. For this purpose,
      two-dimensional nonlinear diffusion filtering (NLDF) was introduced. It was
      applied to CTP images of a CTP phantom for evaluating the accuracy of CBF values
      in low-dose CTP and to clinical low-dose CTP images for determining its
      effectiveness in actual CTP examinations. NLDF successfully reduced the
      statistical noise in the CTP images while preserving the sharp edges. This
      feature generated CBF values close to the reference value, producing reliable CBF
      maps from low-dose CT perfusion images. The CBF maps obtained with NLDF were
      comparable to or better than those obtained by other, commercial CTP software
      programs. The use of NLDF was thus effective for manipulation of low-dose CT
      perfusion images.

PMID- 20821166
TI  - Performance evaluation for 120 four-layer DOI block detectors of the jPET-D4.
AB  - The jPET-D4 is a brain positron emission tomography (PET) scanner that we have
      developed to meet user demands for high sensitivity and high spatial resolution.
      For this scanner, we developed a four-layer depth-of-interaction (DOI) detector.
      The four-layer DOI detector is a key component for the jPET-D4, its performance
      has great influence on the overall system performance. Previously, we reported
      the original technique for encoding four-layer DOI. Here, we introduce the final
      design of the jPET-D4 detector and present the results of an investigation on
      uniformity in performance of the detector. The performance evaluation was done
      over the 120 DOI crystal blocks for the detectors, which are to be assembled into
      the jPET-D4 scanner. We also introduce the crystal assembly method, which is
      simple enough, even though each DOI crystal block is composed of 1,024 crystal
      elements. The jPET-D4 detector consists of four layers of 16 x 16 Gd(2)SiO(5)
      (GSO) crystals and a 256-channel flat-panel position-sensitive photomultiplier
      tube (256ch FP-PMT). To identify scintillated crystals in the four-layer DOI
      detector, we use pulse shape discrimination and position discrimination on the
      two-dimensional (2D) position histogram. For pulse shape discrimination, two
      kinds of GSO crystals that show different scintillation decay time constants are
      used in the upper two and lower two layers, respectively. Proper reflector
      arrangement in the crystal block then allows the scintillated crystals to be
      identified in these two-layer groupings with two 2D position histograms. We
      produced the 120 DOI crystal blocks for the jPET-D4 system, and measured their
      characteristics such as the accuracy of pulse shape discrimination, energy
      resolution, and the pulse height of the full energy peak. The results show a
      satisfactory and uniform performance of the four-layer DOI crystal blocks; for
      example, misidentification rate in each GSO layer is <5% based on pulse shape
      discrimination, the averaged energy resolutions for the central four crystals of
      the first (farthest from the FP-PMT), second, third, and 4th layers are 15.7 +/-
      1.0, 15.8 +/- 0.6, 17.7 +/- 1.2, and 17.3 +/- 1.4%, respectively, and variation
      in pulse height of the full energy peak among the four layers is <5% on average.

PMID- 20821167
TI  - Design of a compensating bolus by use of exhalation CT data for covering residual
      motion in respiratory-gated charged-particle lung therapy: four-dimensional
      carbon beam dose calculation.
AB  - We developed an algorithm which we used to design a compensating bolus by using
      respiratory-gated CT data for respiratory-gated carbon beam lung therapy and
      evaluated it by calculating dose distributions as a function of time. Four
      dimensional CT (4DCT) images were obtained for seven lung cancer patients under
      free breathing conditions. The internal target volume (ITV) was calculated by
      maximum intensity projection processing which use of three types of gross tumor
      volumes (GTVs): at peak exhalation and with a 5 mm shift of the GTV to both
      superior and inferior sides. Then a compensating bolus was designed which use of
      the ITV and applied to 4DCT data at the gating window (around exhalation phase).
      The carbon beam distribution was calculated by a pencil-beam algorithm as a
      function of time. The compensating bolus provides a sufficient prescribed dose to
      the target in the gating window and minimizes any excessive dose to the normal
      tissues. The metric of dosimetric assessment metrics of D95 in all patients is
      greater than 96% of the prescribed dose in the gating window. Our results will be
      beneficial for improving the accuracy of charged-particle radiotherapy for
      hospitals where 4DCT cannot be used.

PMID- 20821168
TI  - Fat quantification by use of phase change in dual-echo magnetic resonance
      imaging.
AB  - The demand for measurement of visceral fat in medical checkups is increasing
      because of attention to central obesity. Computed tomography is widely used for
      this purpose, but carries risks associated with radiation exposure. Fast imaging
      with a dual-echo technique acquiring water and fat signals both in-phase and out
      of-phase using magnetic resonance imaging is desirable, but not all scanners are
      capable of this technique. We tried to quantify fat content by using a dual-echo
      gradient echo pulse sequence with an arbitrary echo time (TE) set. We calculated
      the phase change during the TE interval and extracted the region of fat by
      threshold processing. Variations in the precision of counting fat pixels caused
      by differences between TE1 and TE2 were measured in phantom experiments. We then
      evaluated the validity of this method by examination of a volunteer. The phantom
      study showed a large error when the TE interval was a multiple of the in-phase
      time for fat and water, and the error increased according to the prolongation of
      the TE. In the human study, phase wrapping readily occurred in the phase-change
      image. However, the region of fat was easily extracted with high-pass filtering.
      The fat signal can also be extracted by use of scanners that cannot be set
      simultaneously to in-phase and out-of-phase TE.

PMID- 20821169
TI  - Effect of test patterns on measurement of the luminance of LCD devices by use of
      a telescopic-type luminance meter.
AB  - Quality assurance of electronic display devices is important for maintaining
      reliable soft-copy image interpretations. This paper presents effects of test
      patterns on measurement of the luminance of liquid-crystal display (LCD) devices
      by use of a telescopic-type luminance meter. The luminance for different types of
      test patterns having different backgrounds and measurement areas was measured and
      compared with the results obtained with AAPM task group-18 (TG-18) LN test
      patterns. The luminance measured for the test patterns with a black background
      was lower than that measured for TG-18 LN test patterns due to the light emitted
      from the outside the focused area of the telescopic-type luminance meter. Also,
      the luminance obtained with smaller measurement areas indicated lower luminance.
      These tendencies were particularly obvious at low luminance. The luminance of the
      LCD device by use of a telescopic-type luminance meter should be measured with
      test patterns that have a black background and a smaller measurement area than
      that for the TG-18 LN test patterns.

PMID- 20821170
TI  - Dependence of radiographic sensitivity of CR imaging plate on X-ray tube voltage.
AB  - Our purpose in this study was to compare the energy absorbed in a computed
      radiography (CR) plate with that absorbed by a film-screen system over the
      diagnostic X-ray tube voltage range. A Fuji ST-II and Fuji HGM/UR2 were selected
      as a CR plate and film-screen system, respectively. The X-ray energy absorbed by
      the phosphor layer (per mA per unit area) was calculated theoretically as an
      index of the radiographic sensitivity by use of the incident X-ray photon
      spectrum with the Birch-Marshall formula and the sensitivity spectrum for the
      range of 40-140 kV. The radiosensitive media were treated as layers involving
      mass loading. The relative radiographic sensitivity of the ST-II CR plate best
      approached that of the HGM/UR2 film-screen at 60 kV; it was considerably lower
      for the ST-II CR plate on both sides of 60 kV. The relative sensitivities at 40
      and 140 kV of the ST-II CR plate to the HGM/UR2 film-screen decreased by 16 and
      30%, respectively. This result implies that, in the CR system, the mAs values
      must be increased by 16 and 30% at 40 and 140 kV, respectively. These results
      were explained by the relative positions of the K-absorption edges of the
      phosphors. The theoretically calculated result was in good agreement with the
      experimental result obtained with an acrylic resin phantom. These results would
      be useful in preventing under- or overexposure in a CR system and thus
      controlling the dose administered to the patient.

PMID- 20821171
TI  - Simplified simulation of four-layer depth of interaction detector for PET.
AB  - A four-layer depth-of-interaction (DOI) detector was proposed from and developed
      at the research project at the National Institute of Radiological Sciences in
      Japan, with the aim of achieving high resolution and high spatial sensitivity.
      Previously, we had developed a Monte Carlo simulation for a DOI detector with 2 x
      2 x 4 crystal elements. In this study, in order to simulate the final version of
      the DOI detector of the project, which uses a larger number of crystal elements,
      we have developed a much faster and simpler simulator. In this paper the
      algorithm of the simplified simulator as well as the previously proposed Monte
      Carlo method is presented and the validation of the simplified simulator through
      comparisons with the full Monte Carlo simulation and with some experimental
      results is described.

PMID- 20821172
TI  - Clinical evaluation of a newly developed method for avoiding artifacts caused by
      dental fillings on X-ray CT.
AB  - To evaluate the clinical usefulness of gantry tilt scanning as an image
      reconstruction technique for avoiding artifacts caused by metallic dental
      fillings. Gantry tilt scanning was used with multidetector-row computed
      tomography for imaging in patients with dental fillings. Using a novel PC-based
      program, the oblique images obtained were reconstructed to transverse images
      using nearest neighbor and bilinear interpolation methodologies in order to avoid
      metallic streak artifacts. Coronal images were reformatted with the reconstructed
      transverse images, and the continuity of the reconstructed images was evaluated.
      Gantry tilt scanning was performed in 12 patients with metal artifacts, and the
      original and reconstructed images were classified into four grades and assessed
      by two radiologists. Results of the clinical evaluation indicated that the
      original images with artifacts, only 4% had good image quality in the region
      around the medial pterygoid muscle, only 8% depicted areas around the internal
      carotid artery and internal jugular vein, and only 12% could depict the areas
      around the parotid gland in the clinical evaluation. These values were improved
      to 60, 96, and 100%, respectively, in the reconstructed transverse images. Gantry
      tilt scanning as an image reconstruction technique improves image quality and
      removes most, if not all, artifacts caused by metallic dental fillings. The
      resulting images can be used in the evaluation of oropharyngeal lesions in
      patients with dental fillings.

PMID- 20821173
TI  - Sonographic visualization of the normal stomach: left lateral decubitus position.
AB  - The aim of this study was to evaluate the usefulness of an imaging technique that
      takes into account the effect of posture change on the stomach in transabdominal
      ultrasonography (US). A total of 240 adult patients (healthy subjects) underwent
      gastric US. In all subjects, the lesser curvature of the stomach (LCS) and left
      liver were measured in two different positions [left lateral decubitus (LLD) and
      supine]. The maximal length of the LCS was defined as the measured range between
      the cardial orifice and the left liver tip. The anteroposterior length (L1) and
      maximal longitudinal length (L2) of the left liver were determined on epigastric
      longitudinal scans. The mean LCS in the supine and LLD positions was 90.2 +/-
      34.7 and 124.4 +/- 44.4 mm, respectively. The mean L1 in the supine and LLD
      positions was 54.0 +/- 12.7 and 65.6 +/- 14.4 mm, respectively. The mean L2 in
      the supine and LLD positions was 84.3 +/- 18.5 and 107.0 +/- 25.8 mm,
      respectively. The results for the measured LCS, L1, and L2 differed significantly
      between the supine and LLD positions (P < 0.05). This study demonstrated that the
      LCS could be clearly visualized on longitudinal scanning in the LLD position.
      Therefore, this position may potentially be more useful for gastric US, even in
      view of the limitations of this approach.

PMID- 20821174
TI  - Polyethylene glycol on stability of chitosan microparticulate carrier for
      protein.
AB  - Stability enhancement of protein-loaded chitosan microparticles under storage was
      investigated. Chitosan glutamate at 35 kDa and bovine serum albumin as model
      protein drug were used in this study. The chitosan microparticles were prepared
      by ionotropic gelation, and polyethylene glycol 200 (PEG 200) was applied after
      the formation of the particles. All chitosan microparticles were kept at 25
      degrees C for 28 days. A comparison was made between those preparations with PEG
      200 and without PEG 200. The changes in the physicochemical properties of the
      microparticles such as size, zeta potential, pH, and percent loading capacity
      were investigated after 0, 3, 7, 14, and 28 days of storage. It was found that
      the stability decreased upon storage and the aggregation of microparticles could
      be observed for both preparations. The reduction in the zeta potential and the
      increase in the pH, size, and loading capacity were observed when they were kept
      at a longer period. The significant change of those preparations without PEG 200
      was evident after 7 days of storage whereas those with PEG 200 underwent smaller
      changes with enhanced stability after 28 days of storage. Therefore, this
      investigation gave valuable information on the stability enhancement of the
      microparticles. Hence, enhanced stability of chitosan glutamate microparticles
      for the delivery of protein could be achieved by the application of PEG 200.

PMID- 20821175
TI  - Enhancement of bioavailability of cefpodoxime proxetil using different polymeric
      microparticles.
AB  - Poorly water-soluble drugs such as cefpodoxime proxetil (400 MUg/ml) offer a
      challenging problem in drug formulation as poor solubility is generally
      associated with poor dissolution characteristics and thus poor oral
      bioavailability. According to these characteristics, preparation of cefpodoxime
      proxetil microparticle has been achieved using high-speed homogenization.
      Polymers (methylcellulose, sodium alginate, and chitosan) were precipitated on
      the surface of cefpodoxime proxetil using sodium citrate and calcium chloride as
      salting-out agents. The pure drug and the prepared microparticles with different
      concentrations of polymer (0.05-1.0%) were characterized in terms of solubility,
      drug content, particle size, thermal behavior (differential scanning
      calorimeter), surface morphology (scanning electron microscopy), in vitro drug
      release, and stability studies. The in vivo performance was assessed by
      pharmacokinetic study. The dissolution studies demonstrate a marked increase in
      the dissolution rate in comparison with pure drug. The considerable improvement
      in the dissolution rate of cefpodoxime proxetil from optimized microparticle was
      attributed to the wetting effect of polymers, altered surface morphology, and
      micronization of drug particles. The optimized microparticles exhibited excellent
      stability on storage at accelerated condition. The in vivo studies revealed that
      the optimized formulations provided improved pharmacokinetic parameter in rats as
      compared with pure drug. The particle size of drug was drastically reduced during
      formulation process of microparticles.

PMID- 20821176
TI  - Gene expression profiles of cytosolic heat shock proteins Hsp70 and Hsp90 from
      symbiotic dinoflagellates in response to thermal stress: possible implications
      for coral bleaching.
AB  - Unicellular photosynthetic dinoflagellates of the genus Symbiodinium are the most
      common endosymbionts of reef-building scleractinian corals, living in a symbiotic
      partnership known to be highly susceptible to environmental changes such as
      hyperthermic stress. In this study, we identified members of two major heat shock
      proteins (HSPs) families, Hsp70 and Hsp90, in Symbiodinium sp. (clade C) with
      full-length sequences that showed the highest similarity and evolutionary
      relationship with other known HSPs from dinoflagellate protists. Regulation of
      HSPs gene expression was examined in samples of the scleractinian coral Acropora
      millepora subjected to elevated temperatures progressively over 18 h (fast) and
      120 h (gradual thermal stress). Moderate to severe heat stress at 26 degrees C
      and 29 degrees C (+3 degrees C and +6 degrees C above average sea temperature)
      resulted in an increase in algal Hsp70 gene expression from 39% to 57%, while
      extreme heat stress (+9 degrees C) reduced Hsp70 transcript abundance by 60%
      (after 18 h) and 70% (after 120 h). Elevated temperatures decreased an Hsp90
      expression under both rapid and gradual heat stress scenarios. Comparable Hsp70
      and Hsp90 gene expression patterns were observed in Symbiodinium cultures and in
      hospite, indicating their independent regulation from the host. Differential gene
      expression profiles observed for Hsp70 and Hsp90 suggests diverse roles of these
      molecular chaperones during heat stress response. Reduced expression of the Hsp90
      gene under heat stress can indicate a reduced role in inhibiting the heat shock
      transcription factor which may lead to activation of heat-inducible genes and
      heat acclimation.

PMID- 20821177
TI  - Matrix metalloproteinases (MMP-2,9) and their tissue inhibitors (TIMP-1,2) as
      novel markers of stress response and atherogenesis in children with chronic
      kidney disease (CKD) on conservative treatment.
AB  - The system of matrix metalloproteinases (MMPs) and their tissue inhibitors
      (TIMPs) may play a key role in atherogenesis of chronic kidney disease (CKD)
      patients by its impact on matrix accumulation. Connections with inflammation,
      stress, or endothelial dysfunction are also probable. However, the data on
      correlations between these parameters in CKD patients are scarce in adults and
      absent in children. The aim of our study was to evaluate serum concentrations of
      MMP-2, MMP-9, TIMP-1, and TIMP-2, as well as their correlations with markers of
      stress response (Hsp90-alpha, anti-Hsp60), endothelial dysfunction (sE-selectin),
      and inflammation (high-sensitivity C-reactive protein) in CKD children treated
      conservatively. Thirty-seven patients were divided into two groups according to
      the CKD stage (gr.CKDI, 19 children with CKD stages 2-3; gr.CKDII, 18 subjects
      with CKD stages 4-5). Twenty-four age-matched healthy subjects served as
      controls. Serum concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, Hsp90-alpha, anti
      Hsp60, and sE-selectin were assessed by ELISA. Median values of MMP-2, MMP-9,
      TIMP-1, and TIMP-2 were significantly higher in all CKD children vs. controls and
      were increased in patients with CKD stages 4-5 vs. CKD stages 2-3. Hsp90-alpha,
      anti-Hsp60, sE-selectin, and glomerular filtration rate predicted the values of
      MMPs and TIMPs. Chronic kidney disease in children is characterized by MMP/TIMP
      system dysfunction, aggravated by the progression of renal failure. Correlations
      between examined parameters, heat shock proteins, and markers of endothelial
      damage suggest the possibility of MMP/TIMP application as indicators of stress
      response and atherogenesis in children with CKD on conservative treatment.

PMID- 20821178
TI  - [Prevalence of HIV-TB co-infection and impact of HIV infection on pulmonary
      tuberculosis outcome in Togo].
AB  - The aim of this study was to determine the prevalence of HIV infection in
      tuberculosis patients and its impact on the TB treatment. We enrolled 569
      pulmonary TB patients in four diagnosis and treatment centres in Togo. All
      patients were new TB cases and received the first-line TB drugs: two months of
      rifampicin-pyrazinamide-isoniazid-ethambutol and six months of isoniazid
      ethambutol. HIV testing was done according to the national guidelines, using
      rapid diagnosis tests. The CD4 lymphocyte counting was performed by Facscalibur
      (BD, Sciences) for all HIV-positive patients. Of the 569 TB patients enrolled,
      135 (23.7%) were HIV positive (TB/HIV+). HIV prevalence was 22.4% (76 of 339)
      among men and 25.6% (59 of 230) among women without statistical difference. The
      global rate of treatment success was 82.2%. The rate of treatment success was
      lower (64.3%) in TB/HIV+ patients than in TB/HIV- patients (87.5%) (p <0.01). The
      mortality rates were 25.6% and 11.8% in TB/HIV+ patients and TB/HIV- patients,
      respectively, with a statistically significant difference (p <0.01). We did not
      found any statistical difference between the rates of treatment success among
      TB/HIV- (87.5%) patients and TB/HIV+ patients who had TCD4 lymphocyte counts
      above 200/ul (84.4%). TB program in Togo must take into account HIV infection to
      improve its performance.

PMID- 20821179
TI  - [Change of protocol in the verbal autopsy method and measure of malaria mortality
      in rural areas in Senegal].
AB  - In rural Senegal, three populations have been followed up since several decades
      and the malaria mortality trend has been observed since the mid-1980s. However,
      limits are associated with the verbal autopsy method used to determine causes of
      death, especially deaths due to malaria. A change in protocol occurred in recent
      years in two of these three sites with the involvement of two physicians (instead
      of only one) in the diagnosis. The objective is here to measure its potential
      impact on diagnosis of malaria deaths. Five hundred and fifteen diagnoses
      reported on child deaths occurred from 2000 to 2005 have been analysed. We have
      identified, on the basis of a multinomial logistic regression model, factors
      affecting the determination of malaria deaths among the characteristics of the
      child, the death, the illness and its symptoms, and we also took into account
      method factors. Factors related to the method do not play on the malaria
      diagnosis. This result insures the continuity of the series on malaria mortality
      statistics since 2000 in the two sites despite changes in the method. However,
      the new protocol leads to vanish possibility of having deaths among ill-defined
      or unknown causes. In the African context of absence of health statistics, data
      obtained through the verbal autopsy method in demographic surveillance system can
      provide accurate information in the epidemiological field, even regarding
      malaria.

PMID- 20821180
TI  - [Glossina feeding habits and diversity of species of trypanosomes in an active
      focus of human African trypanosomiasis in Gabon].
AB  - Feeding host is an important factor upon which depend the Glossina infection rate
      and the proportion of different species of trypanosome. Glossina feed both upon
      animals and humans. In order to identify species of trypanosomes present in the
      Komo-Mondah focus and to verify whether there is any relationship between the
      prevalence of sleeping sickness and the feeding habits of Glossina, we have
      carried out an entomological survey in this focus of Gabon. Flies were dissected
      and organs were analysed by PCR, while the origin of blood meals was determined
      by ELISA. Three species of trypanosomes were found: Trypanosoma congolense
      "forest type" (14/104; 13.46%), Trypanosoma vivax (11/104; 10.58%) and
      Trypanosoma brucei s.l. (65/104; 62.5%) with 13.46% (14/104) of mixed infections
      of T. brucei s.l. and T. congolense Glossina palpalis palpalis was caught in all
      biotopes investigated (91.85%) and was infected by all these species of
      trypanosomes. Glossina caliginea was not infected and Glossina fuscipes fuscipes
      was infected by T. brucei s.l. Tsetse flies feed more on animals than on humans
      in almost all villages, but there was no significant difference between the
      number of blood meals taken upon these two groups of vertebrates (Chi 2 = 7.43; p
      > 0.05). A negative correlation was found between the zoophylic/anthropophylic
      index and the prevalence of HAT. This result is insufficient to conclude that
      this index can be used as an indicator of the degree of prevalence of HAT. In
      contrary, the trypanosomian risk seems to be an appropriate indicator of the
      prevalence of HAT in an area. The identification of the reservoir hosts in this
      focus would be useful for a good understanding of the HAT epidemiology.

PMID- 20821181
TI  - [Cortical plasticity and changes in tinnitus: treatment options].
AB  - A growing consensus in current tinnitus research suggests central nervous changes
      as the cause of tinnitus. Several animal and human experimental studies were able
      to show altered tonotopic representations as well as spontaneous activity in the
      auditory cortex. However, a causal relationship between altered
      neurophysiological processes and aspects of tinnitus are still missing.
      Furthermore, it is likely that the importance of diverse processes changes with
      continuing duration of tinnitus. These open questions complicate the development
      of effective treatments. Nevertheless, today several neuroscientifically
      motivated treatments are available, or treatments that can be integrated into a
      neuroscientific framework. This article gives an overview of current
      neuroscientific developments in tinnitus research and discusses their
      implications for the treatment of tinnitus.

PMID- 20821182
TI  - [Atlantoaxial malformation as a rare cause of dysphagia and snoring].
AB  - Abnormalities of the atlantoaxial spine are very rare variants. Bony outgrowths,
      osteophytes, clefts and aplasia may be misinterpreted as degenerative diseases.
      One patient presented with intermittent dysphagia and snoring and CT and MRI
      scans of the cervical spine showed an accessory bone located anterior to the
      atlas and axis. Atlantoaxial anomalies are often incidental findings without
      clinical symptoms. Such changes are rarely the cause of intermittent dysphagia
      and snoring.

PMID- 20821183
TI  - [Sjogren syndrome].
AB  - Sjogren's syndrome (SS) is a chronic inflammatory disorder of hitherto unknown
      origin. The characteristic hallmark of SS is focal lymphocytic infiltration and
      slow destruction of exocrine glands, such as lacrimal and salivary glands. Sicca
      symptoms and/or recurrent parotid gland swelling are often accompanied by
      fatigue. Clinically relevant extraglandular manifestations occur in more than 20%
      of patients with primary SS. The development of malignant B cell lymphoma is the
      most important complication, which affects about 5% of primary SS patients who
      are at higher risk to develop malignant B cell lymphoma, both when compared with
      the general population as well as with patients with SS secondary to other
      systemic autoimmune disorders. Treatment of sicca symptoms is primarily
      symptomatic, whereas glucocorticoids, NSAIDs and/or immunosuppressive drugs may
      be indicated for the treatment of extraglandular manifestations. New therapeutic
      strategies, such as B cell targeted therapies, are in clinical testing especially
      for patients with severe organ manifestations.

PMID- 20821184
TI  - [Rehabilitation for digestive and metabolic diseases. Quo vadis?].
AB  - The position of rehabilitation in gastroenterology, hepatology and metabolic
      diseases has changed little in the last 25 years. Initial improvements in quality
      are oriented more to the content of rehabilitative measures and less to
      organizational basic conditions. Nevertheless, there is an urgent need for action
      if rehabilitation medicine is to achieve an equivalent and recognized position in
      the interaction between primary care and other medical specialties. In this
      article suggestions for expedient prerequisites and utilization options of
      rehabilitation in the fields of hepatogastroenterology and metabolism will be
      presented, which are also oriented to the exemplary implemented concepts from
      Sweden and The Netherlands.

PMID- 20821185
TI  - [Rehabilitation in rheumatology].
AB  - Rehabilitation in rheumatology focuses on prevention of functional disorders of
      the musculoskeletal system, maintenance of working ability and prevention of care
      dependency. Drug treatment alone rarely results in long-term remission, therefore
      rehabilitative measures must be integrated into rheumatic care. Rehabilitative
      therapy in rheumatology includes physiotherapy, patient education and
      occupational therapy. Positive effects of physical therapy methods have been
      proven by various studies. Patient education and occupational therapy are
      important tools for stabilizing the course of the disease. To maintain positive
      rehabilitative results patients have to be involved in the selection of treatment
      measures and should take an active part in the long-term treatment process.
      Despite proven efficacy of physical measures there is evidence for a lack of
      utilization of rehabilitative therapy due to increasing cost pressure in the
      health care system which will further increase over time.

PMID- 20821186
TI  - The cues have it; nest-based, cue-mediated recruitment to carbohydrate resources
      in a swarm-founding social wasp.
AB  - This study explores whether or not foragers of the Neotropical swarm-founding
      wasp Polybia occidentalis use nest-based recruitment to direct colony mates to
      carbohydrate resources. Recruitment allows social insect colonies to rapidly
      exploit ephemeral resources, an ability especially advantageous to species such
      as P. occidentalis, which store nectar and prey in their nests. Although
      recruitment is often defined as being strictly signal mediated, it can also occur
      via cue-mediated information transfer. Previous studies indicated that P.
      occidentalis employs local enhancement, a type of cue-mediated recruitment in
      which the presence of conspecifics at a site attracts foragers. This recruitment
      is resource-based, and as such, is a blunt recruitment tool, which does not
      exclude non-colony mates. We therefore investigated whether P. occidentalis also
      employs a form of nest-based recruitment. A scented sucrose solution was applied
      directly to the nest. This mimicked a scented carbohydrate resource brought back
      by employed foragers, but, as foragers were not allowed to return to the nest
      with the resource, there was no possibility for on-nest recruitment behavior.
      Foragers were offered two dishes--one containing the test scent and the other an
      alternate scent. Foragers chose the test scent more often, signifying that its
      presence in the nest induces naive foragers to search for it off-nest. P.
      occidentalis, therefore, employs a form of nest-based recruitment to carbohydrate
      resources that is mediated by a cue, the presence of a scented resource in the
      nest.

PMID- 20821187
TI  - Conditional ablation of Gsk-3beta in islet beta cells results in expanded mass
      and resistance to fat feeding-induced diabetes in mice.
AB  - AIMS/HYPOTHESIS: Glycogen synthase kinase 3beta (GSK-3beta) is an enzyme that is
      suppressed by insulin and when elevated results in insulin resistance in skeletal
      muscle and diabetes. Its role in beta cell development and function is little
      known. Because of the enzyme's anti-proliferative and pro-apoptotic properties,
      the hypothesis to be tested here was that beta cell specific deficiency of GSK
      3beta in mice would result in enhanced beta cell mass and function. METHODS: Mice
      with beta cell deficiency of GSK-3beta (beta-Gsk-3beta [also known as Gsk3b](-/
      )) were generated by breeding Gsk-3beta (flox/flox) mice with mice overexpressing
      the Cre recombinase gene under the control of the rat insulin 2 gene promoter
      (RIP-Cre mice), and glucose tolerance, insulin secretion, islet mass,
      proliferation and apoptosis were measured. Changes in islet proteins were
      investigated by western blotting. RESULTS: On a normal diet beta-Gsk-3beta ( -/-
      ) mice were found to have mild improvement of glucose tolerance and glucose
      induced insulin secretion, and increased beta cell mass accompanied by increased
      proliferation and decreased apoptosis. On a high-fat diet beta-Gsk-3beta (-/-)
      mice exhibited improved glucose tolerance and expanded beta cell mass with
      increased proliferation relative to that in control mice, resisting fat-fed
      diabetes. Molecular mechanisms accounting for these phenotypic changes included
      increased levels of islet IRS1 and IRS2 proteins and phospho-Akt, suggesting
      enhanced signalling through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway,
      and increased islet levels of pancreas/duodenum homeobox protein 1 (PDX1).
      Inhibition of GSK3 in MIN6 cells in vitro led to increased IRS1 and IRS2 protein
      levels through inhibition of proteosomal degradation. CONCLUSIONS/INTERPRETATION:
      These results are consistent with a mechanism whereby endogenous GSK-3beta
      activity controls islet beta cell growth by feedback inhibition of the insulin
      receptor/PI3K/Akt signalling pathway.

PMID- 20821188
TI  - [Monosegmental anterior lumbar interbody fusion with the SynFix-LRTM device. A
      prospective 2-year follow-up study].
AB  - BACKGROUND: With anterior lumbar interbody fusion (ALIF) alone, the morbidity
      associated with a posterior approach can be avoided. In this study we evaluated
      the use of a PEEK cage with an integrated angle-stable locking plate (SynFix
      LRTM). MATERIAL AND METHODS: Thirty-two patients with osteochondrosis at L4/5 or
      L5/S1 were treated with the SynFix-LRTM. Follow-up at 0, 3, 6, 9, 12, and 24
      months included the Oswestry Disability Index (ODI), visual analog scale (VAS),
      and questions regarding satisfaction and use of pain medication. The fusion rate
      was assessed by X-ray and computed tomography (CT) examination. RESULTS: A
      significant reduction of the ODI and VAS was achieved (p<0.05) with a high rate
      of patient satisfaction. After 2 years, 79% of the patients were able to dispense
      with long-term use of analgesics. We observed a fusion rate of 93% (X-ray) and
      70% (CT) at final follow-up. CONCLUSION: The SynFix-LRTM device is a suitable
      option for the treatment of monosegmental osteochondrosis at L4/5 and L5/S1 with
      comparable or superior results in comparison to posterior or combined fusion
      techniques.

PMID- 20821189
TI  - Posterior dislocation in total knee replacement: a price for deep flexion?
AB  - INTRODUCTION: Post-cam dislocation in TKA is a rare complication after posterior
      stabilized TKA. PURPOSE: Four cases of posterior dislocation of the tibia
      relative to the femur are described in one current posterior stabilized design.
      CONCLUSION: Specific design features in one contemporary high flexion TKA design
      contribute to high dislocation rates.

PMID- 20821190
TI  - High tibial valgus osteotomy in unicompartmental medial osteoarthritis of the
      knee: a retrospective follow-up study over 13-21 years.
AB  - PURPOSE: High tibial osteotomy is a well-established method for the treatment of
      medial unicompartmental osteoarthritis of the knee. METHODS: We analysed
      retrospectively the long-term outcome of open and closing wedge valgisation high
      tibial osteotomies. Out of 71 patients, 54 (76%) were available for the study.
      Survival rates and the influence of the osteotomy type were investigated.
      Secondary outcome measures were the course of radiological leg axis and
      osteoarthritis as well as score outcomes. RESULTS: During a median follow-up of
      16.5 years (IQR 14.5-17.9; range 13-21), 13 patients (24%) underwent conversion
      to total knee arthroplasty; the other 41 patients (76%, survivor group) were
      studied by score follow-up as well as clinical and radiological examinations.
      Osteotomy survival was of 98% after 5 years, 92% after 10 years and 71% after 15
      years. Comparison between open and closing wedge high tibial osteotomy showed no
      significant difference in survival and score outcome. The median Visual Analogue
      Score (VAS) was 0 (IQR 0-1; range 0-4), the Satisfaction Index was 80% (IQR 63
      89; range 30-100), the median Knee Injury and Osteoarthritis Outcome Score was 71
      (IQR 49-82; range 9-100) and the median Western Ontario and McMaster Universities
      Osteoarthritis index was 84 (IQR 66-96; range 9-100). Radiological evaluation
      showed only a slight progression of the degree of osteoarthritis following the
      Kellgren and Lawrence classification. In each case, the axis passed through the
      healthy compartment or at least through the centre of the knee. CONCLUSION: Open
      and closing wedge high tibial osteotomies are a successful choice of treatment
      for unicompartmental degenerative diseases with associated varus in active
      patients. Survival of both techniques is comparable in our series and is
      associated with low pain scores, high satisfaction and high activity levels of
      the survivors.

PMID- 20821191
TI  - Fixation of revision TKA: a review of the literature.
AB  - PURPOSE: Early aseptic loosening is a major complication in revision total knee
      arthroplasty (TKA). It is well accepted that intramedullary stems improve the
      anchoring of the prosthetic components; however, controversy still exists about
      the optimal fixation technique of the stems (cementless, hybrid, cemented).
      METHODS: A literature review was carried out in the main medical databases from
      1980 to 04/2010 to evaluate the available literature by evidence-based criteria
      and to analyse the results of the single studies regarding fixation technique in
      knee revision arthroplasty. RESULTS: There are four studies regarding the
      cementless fixation. Eight studies reported the hybrid technique and five studies
      the cemented technique. Hybrid and cemented techniques are comparable regarding
      the survival of arthroplasties, the rate of aseptic loosening and the clinical
      outcome. However, most studies just show a low level of evidence (LoE III and
      IV), a small to medium number of cases and a short follow-up. CONCLUSION: Based
      on the current literature, no final statement can be drawn regarding the optimal
      fixation technique in revision TKA. Future RCTs are needed to enable conclusive
      statements about the possible advantages and disadvantages of the single fixation
      techniques, although the clinical implementation often is critical.

PMID- 20821192
TI  - High serum total cholesterol is a long-term cause of osteoporotic fracture.
AB  - SUMMARY: Risk factors for osteoporotic fractures were evaluated in 1,396 men and
      women for a period of 20 years. Serum total cholesterol was found to be an
      independent osteoporotic fracture risk factor whose predictive power improves
      with time. INTRODUCTION: The purpose of this study was to evaluate long-term risk
      factors for osteoporotic fracture. METHODS: A population random sample of men and
      women aged 25-64 years (the Gothenburg WHO MONICA project, N = 1,396, 53% women)
      was studied prospectively. The 1985 baseline examination recorded physical
      activity at work and during leisure time, psychological stress, smoking habits,
      coffee consumption, BMI, waist/hip ratio, blood pressure, total, HDL and LDL
      cholesterol, triglycerides, and fibrinogen. Osteoporotic fractures over a period
      of 20 years were retrieved from the Gothenburg hospital registers. Poisson
      regression was used to analyze the predictive power for osteoporotic fracture of
      each risk factor. RESULTS: A total number of 258 osteoporotic fractures occurred
      in 143 participants (10.2%). As expected, we found that previous fracture,
      smoking, coffee consumption, and lower BMI each increase the risk for
      osteoporotic fracture independently of age and sex. More unexpectedly, we found
      that the gradient of risk of serum total cholesterol to predict osteoporotic
      fracture significantly increases over time (p = 0.0377). CONCLUSIONS: Serum total
      cholesterol is an independent osteoporotic fracture risk factor whose predictive
      power improves with time. High serum total cholesterol is a long-term cause of
      osteoporotic fracture.

PMID- 20821193
TI  - Tellurite-induced carbonylation of the Escherichia coli pyruvate dehydrogenase
      multienzyme complex.
AB  - The soluble tellurium oxyanion, tellurite, is toxic for most organisms. At least
      in part, tellurite toxicity involves the generation of oxygen-reactive species
      which induce an oxidative stress status that damages different macromolecules
      with DNA, lipids and proteins as oxidation targets. The objective of this work
      was to determine the effects of tellurite exposure upon the Escherichia coli
      pyruvate dehydrogenase (PDH) complex. The complex displays two distinct enzymatic
      activities: pyruvate dehydrogenase that oxidatively decarboxylates pyruvate to
      acetylCoA and tellurite reductase, which reduces tellurite (Te(4+)) to elemental
      tellurium (Te(o)). PDH complex components (AceE, AceF and Lpd) become oxidized
      upon tellurite exposure as a consequence of increased carbonyl group formation.
      When the individual enzymatic activities from each component were analyzed, AceE
      and Lpd did not show significant changes after tellurite treatment. AceF activity
      (dihydrolipoil acetyltransferase) decreased ~30% when cells were exposed to the
      toxicant. Finally, pyruvate dehydrogenase activity decreased >80%, while no
      evident changes were observed in complex's tellurite reductase activity.

PMID- 20821194
TI  - Chromate reductase activity of the Paracoccus denitrificans ferric reductase B
      (FerB) protein and its physiological relevance.
AB  - The homodimeric flavoprotein FerB of Paracoccus denitrificans catalyzed the
      reduction of chromate with NADH as electron donor. When present, oxygen was
      reduced concomitantly with chromate. The recombinant enzyme had a maximum
      activity at pH 5.0. The stoichiometric ratio of NADH oxidized to chromate reduced
      was found to be 1.53 +/- 0.09 (O(2) absent) or > 2 (O(2) present), the apparent K
      (M) value for chromate amounted to 70 +/- 10 MUM with the maximum rate of 2.9 +/-
      0.3 MUmol NADH s(-1) (mg protein)(-1). Diode-array spectrophotometry and
      experiments with one-electron acceptors provided evidence for oxygen consumption
      being due to a flavin semiquinone, formed transiently during the interaction of
      FerB with chromate. At the whole-cell level, a ferB mutant strain displayed only
      slightly diminished rate of chromate reduction when compared to the wild-type
      parental strain. Anaerobically grown cells were more active than cells grown
      aerobically. The activity could be partly inhibited by antimycin, suggesting an
      involvement of the respiratory chain. Chromate concentrations above ten
      micromolars transiently slowed or halted culture growth, with the effect being
      more pronounced for the mutant strain. It appears, therefore, that, rather than
      directly reducing chromate, FerB confers a protection of cells against the
      oxidative stress accompanying chromate reduction. With a strain carrying the
      chromosomally integrated ferB promoter-lacZ fusion, it was shown that the ferB
      gene is not inducible by chromate.

PMID- 20821195
TI  - Antimicrobial activity and occurrence of bacteriocin structural genes in
      Enterococcus spp. of human and animal origin isolated in Portugal.
AB  - The main objective of this study was to detect the antimicrobial activity and the
      presence of bacteriocin structural genes in 224 enterococcal isolates from fecal
      origin obtained from humans, pets, wild animals and birds. Direct antimicrobial
      activity against Listeria monocytogenes CECT4032 was detected in 102 (45.6%) of
      the tested isolates. From these, only 22 displayed bacteriocin activity against
      this indicator. The bacteriocinogenic strains contained one or more of the
      bacteriocin structural genes tested in this study, with those of enterocins P, A
      and L50 (L50A and L50B) being the most abundant. Our results show a high
      occurrence of the combination of different bacteriocin structural genes in the
      enterococcal isolates analyzed, indicating an elevated genetic potential of these
      strains to produce various bacteriocins.

PMID- 20821196
TI  - Organic acid production and plant growth promotion as a function of phosphate
      solubilization by Acinetobacter rhizosphaerae strain BIHB 723 isolated from the
      cold deserts of the trans-Himalayas.
AB  - An efficient phosphate-solubilizing plant growth-promoting Acinetobacter
      rhizosphaerae strain BIHB 723 exhibited significantly higher solubilization of
      tricalcium phosphate (TCP) than Udaipur rock phosphate (URP), Mussoorie rock
      phosphate (MRP) and North Carolina rock phosphate (NCRP). Qualitative and
      quantitative differences were discerned in the gluconic, oxalic, 2-keto gluconic,
      lactic, malic and formic acids during the solubilization of various inorganic
      phosphates by the strain. Gluconic acid was the main organic acid produced during
      phosphate solubilization. Formic acid production was restricted to TCP
      solubilization and oxalic acid production to the solubilization of MRP, URP and
      NCRP. A significant increase in plant height, shoot fresh weight, shoot dry
      weight, root length, root dry weight, and root, shoot and soil phosphorus (P)
      contents was recorded with the inoculated treatments over the uninoculated NP(0)K
      or NP(TCP)K treatments. Plant growth promotion as a function of phosphate
      solubilization suggested that the use of bacterial strain would be a beneficial
      addition to the agriculture practices in TCP-rich soils in reducing the
      application of phosphatic fertilizers.

PMID- 20821198
TI  - Paediatric investigation plans for pain: painfully slow!
AB  - PURPOSE: To examine the early impact of the Paediatric Regulation, which entered
      into force in Europe on 27 January 2007, on the development of pharmaceutical
      drugs in the therapeutic field of pain submitted to the Paediatric Committee
      (PDCO) and to the European Medicines Agency (EMA). METHODS: Paediatric
      Investigations Plans (PIPs) submitted with a Decision (outcome) reached between
      September 2007 and March 2010 were included in the analysis. RESULTS: Of the 17
      Paediatric Investigation Plans submitted, 14 have resulted in an EMA Decision, 3
      were withdrawn by the applicants, 8 were granted a full waiver from development,
      and 1 resulted in a negative opinion. Decisions as issued included 15 clinical
      trials, with at least 1,282 children to be recruited into studies across five
      different products. Neonates were included in four of the products. CONCLUSIONS:
      The small number of submissions indicates a lack of new drugs being developed for
      the management of pain. Ethical concerns that too many vulnerable children will
      be recruited into clinical trials must be balanced against limiting the number of
      off-label prescribing and obtaining age-appropriate information on paediatric
      use. Now is an opportune time for clinicians, academics, learned societies and
      industry to collaborate for the benefit of children in pain.

PMID- 20821197
TI  - Event-related desynchronization of motor cortical oscillations in patients with
      multiple system atrophy.
AB  - Multiple system atrophy (MSA) is a progressive neurodegenerative disease
      characterized by parkinsonism (MSA-P), cerebellar and autonomic deficits. In
      Parkinson's disease (PD), an impaired modulation of motor cortical mu and beta
      range oscillations may be related to the pathophysiology of bradykinesia. Event
      related desynchronization (ERD) of these oscillations occur for 1-2 s preceding a
      voluntary movement in normal subjects and patients with PD treated with levodopa
      while only lasting around 0.5 s in untreated patients. Motor cortical rhythms
      were recorded from subdural strip electrodes in three patients with MSA-P while
      taking their regular dopaminergic medications. Following a ready cue, patients
      performed an externally cued wrist extension movement to a go cue. In addition,
      recordings were obtained during imagined wrist extension movements to the same
      cues and during self-paced wrist extensions. ERD and event-related
      synchronization were examined in subject-specific frequency bands. All patients
      showed movement-related ERD in subject-specific frequency bands below ~40 Hz in
      both externally cued and self-paced conditions. Preparatory ERD latency preceding
      self-cued movement was 900 ms in one patient and at or after movement onset in
      the other two patients. In the externally cued task, a short lasting (<1.3 s)
      ready cue-related ERD that was not sustained to movement onset was observed in
      two patients. Imagined movements resulted in go cue-related ERD with a smaller
      magnitude in the same two patients. These results indicate that the modulation of
      motor cortical oscillations in patients with MSA that are treated with levodopa
      is similar to that occurring in untreated patients with PD. The findings suggest
      that cortical activation in patients with MSA is diminished, may be related to
      pathophysiological changes occurring in the basal ganglia and correlates with the
      poor clinical response that these patients typically obtain with dopaminergic
      therapy.

PMID- 20821199
TI  - Formation of very large conductance channels by Bacillus cereus Nhe in Vero and
      GH(4) cells identifies NheA + B as the inherent pore-forming structure.
AB  - The nonhemolytic enterotoxin (Nhe) produced by Bacillus cereus is a pore-forming
      toxin consisting of three components, NheA, -B and -C. We have studied effects of
      Nhe on primate epithelial cells (Vero) and rodent pituitary cells (GH(4)) by
      measuring release of lactate dehydrogenase (LDH), K(+) efflux and the cytosolic
      Ca(2+) concentration ([Ca(2+)](i)). Plasma membrane channel events were monitored
      by patch-clamp recordings. Using strains of B. cereus lacking either NheA or -C,
      we examined the functional role of the various components. In both cell types,
      NheA + B + C induced release of LDH and K(+) as well as Ca(2+) influx. A specific
      monoclonal antibody against NheB abolished LDH release and elevation of
      [Ca(2+)](i). Exposure to NheA + B caused a similar K(+) efflux and elevation of
      [Ca(2+)](i) as NheA + B + C in GH(4) cells, whereas in Vero cells the rate of
      K(+) efflux was reduced by 50% and [Ca(2+)](i) was unaffected. NheB + C had no
      effect on either cell type. Exposure to NheA + B + C induced large-conductance
      steps in both cell types, and similar channel insertions were observed in GH(4)
      cells exposed to NheA + B. In Vero cells, NheA + B induced channels of much
      smaller conductance. NheB + C failed to insert membrane channels. The conductance
      of the large channels in GH(4) cells was about 10 nS. This is the largest channel
      conductance reported in cell membranes under quasi-physiological conditions. In
      conclusion, NheA and NheB are necessary and sufficient for formation of large
      conductance channels in GH(4) cells, whereas in Vero cells such large-conductance
      channels are in addition dependent on NheC.

PMID- 20821200
TI  - Minimally invasive percutaneous nephrolithotomy with multiple mini tracts in a
      single session in treating staghorn calculi.
AB  - There has been continuing controversy regarding multiple tracts in a percutaneous
      nephrolithotomy (PCNL) session that may bring more complications, especially
      severe bleeding need for transfusion, even nephrectomy. Little tracts may bring
      less trauma to renal parenchyma than standard PCNL tracts. We carried minimally
      invasive PCNL (MPCNL) in treating staghorn calculi with multiple 16Fr
      percutaneous tracts in a single session, in an attempt to get high stone free
      with little trauma, and compared the morbidity of standard PCNL procedures in a
      prospective trial. A total of 54 consecutive patients with staghorn calculi were
      prospectively randomized for MPCNL (29) and PCNL (25). The size and location of
      stone, operative parameters, number of tracts, stone-free rate, operating time,
      hospital stay and complications were analyzed. In MPCNL group, a total of 67
      percutaneous tracts were established in 29 renal units, while 28 tracts in 25
      renal units in PCNL group. Compared to PCNL, MPCNL was associated with higher
      clearance rate (89.7 vs. 68%, p = 0.049), less chance need for adjunctive
      procedure of SWL or second-look PCNL (24.1 vs. 60%, p = 0.007), while a similar
      complication rate (37.9 vs. 52%, p = 0.300). In conclusion, with the development
      of instruments and increased experience, judiciously made multiple percutaneous
      tracts in a single session of MPCNL for treating staghorn calculi were safe,
      feasible and efficient with an acceptable morbidity.

PMID- 20821201
TI  - Pediatric hemiplegic migraine: susceptibility weighted and MR perfusion imaging
      abnormality.
AB  - We report on an 11-year-old girl suffering from a typical attack of hemiplegic
      migraine with characteristic abnormalities in perfusion MR and susceptibility
      weighted MR imaging findings. The imaging abnormalities were resolved 48 h after
      the attack. Susceptibility-weighted MR imaging findings correlated well with the
      MR perfusion, thus it can be used along with conventional MRI for evaluation of
      children with complex migraine attacks. Susceptibility-weighted MR imaging might
      have a diagnostic role in assessing the vascular events in hemiplegic migraine.

PMID- 20821202
TI  - Hydrogen formation by an arsenate-reducing Pseudomonas putida, isolated from
      arsenic-contaminated groundwater in West Bengal, India.
AB  - Anaerobic growth of a newly isolated Pseudomonas putida strain WB from an arsenic
      contaminated soil in West Bengal, India on glucose, L: -lactate, and acetate
      required the presence of arsenate, which was reduced to arsenite. During aerobic
      growth in the presence of arsenite arsenate was formed. Anaerobic growth of P.
      putida WB on glucose was made possible presumably by the non-energy-conserving
      arsenate reductase ArsC with energy derived only from substrate level
      phosphorylation. Two moles of acetate were generated intermediarily and the
      reducing equivalents of glycolysis and pyruvate decarboxylation served for
      arsenate reduction or were released as H(2). Anaerobic growth on acetate and
      lactate was apparently made possible by arsenate reductase ArrA coupled to
      respiratory electron chain energy conservation. In the presence of arsenate, both
      substrates were totally oxidized to CO(2) and H(2) with part of the H(2) serving
      for respiratory arsenate reduction to deliver energy for growth. The growth yield
      for anaerobic glucose degradation to acetate was Y (Glucose) = 20 g/mol, leading
      to an energy coefficient of Y (ATP) = 10 g/mol adenosine-5'-triphosphate (ATP),
      if the Emden-Meyerhof-Parnas pathway with generation of 2 mol ATP/mol glucose was
      used. During growth on lactate and acetate no substrate chain phosphorylation was
      possible. The energy gain by reduction of arsenate was Y (Arsenate) = 6.9 g/mol,
      which would be little less than one ATP/mol of arsenate.

PMID- 20821203
TI  - Metabolic fluxes and beyond-systems biology understanding and engineering of
      microbial metabolism.
AB  - The recent years have seen tremendous progress towards the understanding of
      microbial metabolism on a higher level of the entire functional system. Hereby,
      huge achievements including the sequencing of complete genomes and efficient post
      genomic approaches provide the basis for a new, fascinating era of research
      analysis of metabolic and regulatory properties on a global scale. Metabolic flux
      (fluxome) analysis displays the first systems oriented approach to unravel the
      physiology of microorganisms since it combines experimental data with metabolic
      network models and allows determining absolute fluxes through larger networks of
      central carbon metabolism. Hereby, fluxes are of central importance for systems
      level understanding because they fundamentally represent the cellular phenotype
      as integrated output of the cellular components, i.e. genes, transcripts,
      proteins, and metabolites. A currently emerging and promising area of research in
      systems biology and systems metabolic engineering is therefore the integration of
      fluxome data in multi-omics studies to unravel the multiple layers of control
      that superimpose the flux network and enable its optimal operation under
      different environmental conditions.

PMID- 20821204
TI  - Structural and functional analysis of hybrid enzymes generated by domain
      shuffling between Saccharomyces cerevisiae (var. diastaticus) Sta1 glucoamylase
      and Saccharomycopsis fibuligera Bgl1 beta-glucosidase.
AB  - Saccharomyces cerevisiae Sta1 glucoamylase and Saccharomycopsis fibuligera Bgl1
      beta-glucosidase, two relevant enzymes from a biotechnological point of view, are
      proteins with multidomain structure. Starting with homology-based structural
      models of Sta1 and Bgl1, we have constructed a series of hybrid enzymes by
      interchanging domains of the two proteins. The first purpose of these constructs
      was to check available hypotheses about the uncertain biological functions of two
      domains: the serine/threonine-rich domain (STRD) of Sta1 and a beta-sandwich
      domain present in Bgl1 that we have designated fibronectin-like domain (FLD).
      While, according to the initial hypothesis, proteins carrying the FLD tend to
      adhere to the cell wall, our results argued against the idea of an involvement of
      the STRD in protein secretion that stemmed from the presence of similar domains
      in different proteins secreted by yeast. The second objective of this work was to
      increase the enzymatic repertoire by generating enzymes with new structural and
      functional properties.

PMID- 20821205
TI  - A molecular approach to optimize hIFN alpha2b expression and secretion in
      Yarrowia lipolytica.
AB  - In this work, we investigated the effect of codon bias and consensus sequence
      (CACA) at the translation initiation site on the expression level of heterologous
      proteins in Yarrowia lipolytica; human interferon alpha 2b (hIFN-alpha2b) was
      studied as an example. A codon optimized hIFN-alpha2b gene was synthesized
      according to the frequency of codon usage in Y. lipolytica. Both wild-type (IFN
      wt) and optimized hIFN-alpha2b (IFN-op) genes were expressed under the control of
      a strong inducible promoter acyl-co-enzyme A oxidase (POX2). Protein secretion
      was directed by the targeting sequence of the extracellular lipase (LIP2): pre
      proLIP2. Codon optimization increased protein production by 11-fold, whereas the
      insertion of CACA sequence upstream of the initiation codon of IFN-op construct
      resulted in 16.5-fold increase of the expression level; this indicates that
      translational efficiency plays an important part in the increase of hIFN-alpha2b
      production level. The replacement of the pre-proLIP2 signal secretion with the
      LIP2 pre-region sequence followed by the X-Ala/X-Pro stretch but without the pro
      region also increased the secretion of the target protein by twofold, suggesting
      therefore that the LIP2 pro-region is not necessary for extracellular secretion
      of small heterologous proteins in Yarrowia lipolytica.

PMID- 20821206
TI  - On the effectiveness of recombinant human TSH as a stimulating agent for 131I
      treatment of metastatic differentiated thyroid cancer.

PMID- 20821207
TI  - 99mTc-tetrofosmin SPECT for the evaluation of cerebral lesions.

PMID- 20821208
TI  - A new PET probe, (18)F-tetrafluoroborate, for the sodium/iodide symporter:
      possible impacts on nuclear medicine.

PMID- 20821209
TI  - Breast lymphatic drainage via the pulmonary lymphatic system.

PMID- 20821210
TI  - Is a SUV cut-off necessary in the evaluation of the response of axillary lymph
      node metastases to neoadjuvant therapy?

PMID- 20821211
TI  - Transcatheter arterial chemoembolization with epirubicin-loaded superabsorbent
      polymer microspheres for 135 hepatocellular carcinoma patients: single-center
      experience.
AB  - PURPOSE: To evaluate the safety, clinical outcomes, and hepatic artery damage
      after transcatheter arterial chemoembolization (TACE) with epirubicin-loaded
      superabsorbent polymer microspheres (ELM-TACE) in patients with hepatocellular
      carcinoma (HCC) in a single center in Japan. MATERIALS AND METHODS: This embolic
      agent is the original form of microspheres, which has the same composition and
      nature as HepaSpheres. Between May 2007 and June 2009, 135 patients with
      unresectable HCC who underwent ELM-TACE were enrolled. Embolization through
      extrahepatic collaterals was performed in 27 (20.0%) patients. Tumor response was
      evaluated using European Association for the Study of the Liver criteria at 1 and
      6 months after initial ELM-TACE. RESULTS: All procedures were successfully
      performed. The median number of TACE per patient was 1.7 sessions (range 1-5),
      and the mean epirubicin dose per session was 19.7 mg (range 2.0-60.0). Local
      pooling within target tumors was observed during TACE in 34 (25.2%) patients, and
      in 14 (10.4%) of the patients, gelatin sponge particles were added after the
      microspheres until each pooling disappeared. No serious adverse events associated
      with TACE occurred, and the incidence of postembolization syndrome was <=17.8%.
      The 1- and 6-month tumor response rates were 56.3 and 52.6%, respectively. The
      overall 1- and 2-year survival rates were 73.7 and 59.0%, respectively. Among 99
      evaluated patients, 90 (90.9%) were found to have no hepatic artery damage after
      initial ELM-TACE. CONCLUSION: ELM-TACE is safe and effective treatment for
      unresectable HCC and is associated with low frequency of postembolization
      syndrome and minimal damage to the hepatic artery.

PMID- 20821212
TI  - The balance between soluble receptors regulating IL-6 trans-signaling is
      predictive for the RANKL/osteoprotegerin ratio in postmenopausal women with
      rheumatoid arthritis.
AB  - The objective of this study is to investigate the relationship between soluble
      components of the interleukin 6 (IL-6) system mediating and modifying IL-6 trans
      signaling and the RANKL-RANK-osteoprotegerin system in postmenopausal women with
      rheumatoid arthritis (RA). The following parameters were investigated in 126
      postmenopausal women with RA: IL-6, soluble IL-6-receptor (sIL-6R), soluble
      glycoprotein 130 (sgp130), sRANKL, osteoprotegerin (OPG), osteocalcin,
      erythrocyte sedimentation rate and C-reactive protein in sera, pyridinolin and
      desoxypyridinolin crosslinks in the morning urine. Bone mineral density (BMD) was
      measured by dual X-ray absorptiometry at the lumbar spine (BMD-LS) and at the
      femoral neck (BMD-FN). Predictors of RANKL/OPG ratio and BMD were evaluated by
      multiple linear regression analysis. The following determinants of the RANKL/OPG
      ratio were identified: sIL-6R/sgp130 ratio and daily glucocorticoid (GC) dose as
      positive determinants in the whole group (R (2) = 0.56; P = 0.001), sIL-6R/sgp130
      ratio as the exclusive positive determinant in patients with GC therapy (R (2) =
      0.48; P = 0.001) and sgp130 as negative determinant in patients without GC (R (2)
      = 0.42; P = 0.031). Sgp130 was highly significantly positively correlated with
      OPG in the whole group (P < 0.001) as well as in patients with (n = 70; P < 0.05)
      and without GC therapy (n = 56; P < 0.01). sIL-6R was the main negative predictor
      of BMD-LS (R (2) = 0.41; P = 0.019). High sIL-6R/sgp130 ratio and/or low sgp130
      are associated with a high sRANKL/OPG ratio in sera of postmenopausal women with
      RA indicating the critical significance of IL-6 trans-signaling for an increase
      in the RANKL/OPG ratio and of bone resorption. Inhibition of IL-6 trans-signaling
      may be an effective bone-protecting principle in postmenopausal women with RA.

PMID- 20821213
TI  - Heat shock modulates phosphorylation status and activity of nucleoside
      diphosphate kinase in cultured sugarcane cells.
AB  - Nucleoside diphosphate kinase (NDPK) is involved in the regeneration of
      nucleoside triphosphates (NTPs) through its phosphotransferase activity via an
      autophosphorylating histidine residue. Additionally, autophosphorylation of
      serine and/or threonine residues is documented for NDPKs from various organisms.
      However, the metabolic significance of serine/threonine phosphorylation has not
      been well characterized. In this study we report the cloning and characterization
      of NDPKI from cultured sugarcane (Saccharum officinarum L. line H50-7209) cells,
      and modulation of serine autophosphorylation of NDPK1 in response to heat-shock
      (HS). Heat-shock treatment at 40 degrees C for 2 h resulted in a 40% reduction in
      labeled phosphoserine in NDPK1. This dephosphorylation was accompanied by an
      increase in NDPK enzyme activity. In contrast, NDPK1 in cultured tobacco (cv. W
      38) cells did not show changes in autophosphorylation or increased enzyme
      activity in response to HS. The mRNA or protein level of NDPK1 did not increase
      in response to HS. Sugarcane cells sustain the constitutive protein synthesis in
      addition to heat-shock protein synthesis during HS, while constitutive protein
      synthesis is significantly reduced in tobacco cells during HS. Thus, HS
      modulation of NDPK1 activity and serine dephosphorylation in sugarcane cells may
      represent an important physiological role in maintaining cellular metabolic
      functions during heat stress.

PMID- 20821214
TI  - Obscure manifestations of Salmonella subdural empyema in children: case report
      and literature review.
AB  - PURPOSE: Salmonella intracranial infections, including subdural empyema and brain
      abscess, are rare clinical manifestations in children. The aim of this study is
      to investigate the clinical course of Salmonella subdural empyema in infants and
      children. METHODS: We report a 9-month-old female infant diagnosed as Salmonella
      subdural empyema with clinical features of prolonged fever for more than 2 months
      and episodic focal seizures. Literature published between 1986 and 2010 relevant
      to Salmonella subdural empyema in children were reviewed. The clinical
      presentations and laboratory findings were analyzed. RESULTS: Seventeen cases
      with Salmonella subdural empyema, including our index case, has been reported
      with detailed clinical presentation. Fever (17/17; 100%), symptoms and signs of
      increased intracranial pressure (8/17; 47%), seizures (8/17; 47%), and limb
      paralysis (8/17; 47%) were the most frequent clinical features. Among these
      cases, unknown causative organism prior to surgery (11/17; 65%) and prolonged
      fever for more than 3 weeks (5/17; 29%) were also noticed. Sixteen out of 17
      patients (94%) required surgical intervention for treatment. The morbidity rate
      and mortality rate were 29% (5/17) and 6% (1/17), respectively. CONCLUSION:
      Subdural empyema is considered to be a disease with rapid progression. However,
      the cases caused by Salmonella species may present a slow disease course.
      Surgical intervention is sometimes the only way to detect the pathogen.

PMID- 20821215
TI  - Detection of RASA1 mutations in patients with sporadic Sturge-Weber syndrome.
AB  - OBJECTIVE: The aim of this study was to identify RASA1 mutation in Chinese
      population with sporadic Sturge-Weber syndrome (SWS). METHODS: Genomic DNA was
      obtained from peripheral blood of nine patients with sporadic SWS. The 25 exons,
      promoter regions (-1,000 bp) as well as intron-exon boundaries of RASA1 were
      amplified by polymerase chain reaction, and products were sequenced directly.
      RESULTS: A novel synonymous mutation (c.1229 G > A [p.K420K]) of RASA1 was
      identified in the present series. CONCLUSION: It implied that RASA1 may be not a
      virulence gene, but further study is needed to know RASA1 gene mutation in SWS
      patients.

PMID- 20821216
TI  - Octreotide in the treatment of neonatal postoperative chylothorax: report of
      three cases and literature review.
AB  - Chylothorax is a well-recognized complication after neonatal cardiothoracic
      surgery. Management strategies include cessation of enteral feedings, repeated
      aspiration, chest drainage, and total parenteral nutrition. Somatostatin and its
      analogue, octreotide, have been used with promising results. The authors present
      three cases of neonatal postoperative chylothorax in which octreotide was used.
      After literature review, we can say that octreotide is relatively safe, and may
      reduce clinical course and complications associated with neonatal postoperative
      chylothorax. One should be aware of possible association between octreotide and
      necrotizing enterocolitis. Prospective controlled trials supporting octreotide
      use are lacking.

PMID- 20821217
TI  - Elevated preoperative neutrophil to lymphocyte ratio predicts risk of recurrence
      following curative resection for stage IIA colon cancer.
AB  - BACKGROUND AND OBJECTIVES: Adjuvant chemotherapy for stage II colon cancer
      remains controversial but may be considered for patients with high-risk features.
      Recent studies have shown that elevated neutrophil to lymphocyte ratio (NLR) is a
      worse prognostic factor and a predictor of response to chemotherapy in patients
      with advanced colorectal cancer. The purpose of this study was to evaluate
      whether NLR predicts risk of recurrence in patients with stage IIA colon cancer
      undergoing curative resection without adjuvant chemotherapy. METHODS: We
      retrospectively reviewed 141 consecutive patients with stage IIA colon cancer
      treated with curative surgery alone from 2002 to 2006. NLR, as well as
      demographics, clinical, histopathologic, and laboratory data were analyzed.
      Univariate and multivariate analyses were conducted to identify prognostic
      factors associated with recurrent-free survival (RFS). RESULTS: Cox's regression
      analysis demonstrated that elevated NLR (>4) (hazard ratio, 4.88; P < 0.01) and
      less lymph node sampling (<15 lymph nodes; hazard ratio, 3.80; P < 0.05) were
      adverse prognostic factors for RFS. The 5-year RFS was 91.4% (95% CI, 88.6-94.2%)
      for patients with normal NLR and 63.8% (51.1-76.3%) for patients with elevated
      NLR. The 5-year RFS for patients with 0, 1, and 2 of the identified risk factors
      was 95.1%, 87.4%, and 33.3%, respectively (P < 0.001). CONCLUSIONS: Elevated
      preoperative NLR is an independent predictor of worse RFS for patients with stage
      IIA colon cancer and a potential biomarker to identify candidates for adjuvant
      chemotherapy.

PMID- 20821218
TI  - The inter-observer reliability is very low at clinical examination of parastomal
      hernia.
AB  - INTRODUCTION: Parastomal hernia in patients with a permanent colostomy is common.
      The aim of this study was to evaluate the reliability of the diagnosis based on
      clinical examination and to compare this examination with the result of a
      specially designed questionnaire and computerised tomography (CT) scan. METHODS:
      Forty-one patients operated upon with an abdominoperineal resection due to rectal
      cancer at three hospitals between 1996 and 2002 were included. At minimum of 4
      years after the operation, they underwent clinical examination by two or three
      independent surgeons, answered a colostomy questionnaire and were offered a CT
      scan of the abdominal wall. RESULT: At Hospital I, 17 patients were examined by
      three surgeons, with inter-observer kappa values between 0.35 and 0.64. At
      Hospital II, 13 patients were examined by three surgeons, the kappa values ranged
      between 0.29 and 0.43. At Hospital III, 11 patients were examined by two
      surgeons, with kappa value of 0.73. The kappa value between CT scan and the
      colostomy questionnaire was 0.45. CONCLUSION: The inter-observer reliability was
      low, indicating that parastomal hernia is difficult to diagnose by patient
      history and clinical examination. Some herniae may not be detected by CT scan,
      and the correlation to patient-reported complaints is low. A more sensitive
      radiological method to detect parastomal hernia is needed.

PMID- 20821219
TI  - Assessment of left atrial volume: a focus on echocardiographic methods and
      clinical implications.
AB  - Left atrial enlargement is an important predictor of cardiovascular events such
      as atrial fibrillation, stroke, heart failure and mortality. A number of methods
      of left atrial size assessment by echocardiography have been reported, from the
      simple antero-posterior diameter in the parasternal long axis view to the more
      complex ellipsoid, area-length and Simpson's method of estimating left atrial
      volume. These different methods of left atrial size assessment, their clinical
      implications and some common pitfalls are discussed in this review.

PMID- 20821220
TI  - [History of the German Society of Rheumatology 1947-2007].
AB  - The "German Society of Rheumatology" was founded in Bad Neuenahr in the Federal
      Republic of Germany In 1947. The society perceived itself as the successor to the
      "German Society for the Abatement of Rheumatism". The primary aim of the society
      was close cooperation with other German-speaking rheumatological societies in
      Austria and Switzerland. The establishment of the European Rheumatism Congress in
      Wiesbaden in 1979 represented the society's highpoint on the way to international
      recognition. In the 1980s serious conflict developed within the society which
      could be resolved without the divisions taking real form. The 1990s were
      characterized by organizational changes, with the help of which the society hopes
      to confront changing conditions in the health system.

PMID- 20821221
TI  - [History of the Society of Rheumatology in the GDR 1945/49 to 1990].
AB  - Rheumatology's comeback in the GDR saw the establishment of a rheumatology
      research institute in Dresden, built up by Hans Tichy (1888-1970). It was here
      that initial success was seen in the treatment of rheumatic fever, mainly as a
      result of strict relapse prevention with the administration of penicillin. A
      working group of the "Society for Clinical Medicine in the GDR" was the
      forerunner to what turned in 1967 into the autonomous "Society of Rheumatology of
      the GDR". The latter worked closely with rheumatology societies in Eastern
      European countries. Their shared centre of coordination was in Moscow.
      International symposia took place with participants from Czechoslovakia, Poland
      and Hungary, but also with delegations from Switzerland, Austria and the Federal
      Republic of Germany. The Society of Rheumatology of the GDR merged with the West
      German Society of Rheumatology in September 1990.

PMID- 20821222
TI  - [History of the German Society for the Abatement of Rheumatism 1927-1945].
AB  - The need to unite physicians working in the field of rheumatology in a medical
      society became clear following statistical analysis in the 1920s, which showed
      the significant economic loss resulting rheumatological disease. An international
      association of physicians active in the field of balneology was established in
      1926 in Piestany in today's Slovakia. In 1927, the "German Section of the
      International Committee of Research and Therapy of Rheumatism" was founded in Bad
      Schreiberhau. In August 1927, the section changed into the "German Society for
      the Abatement of Rheumatism". The takeover of the National Socialists lead to a
      reorganisation of the society. The leaders insisted on a change in the previous
      democratic constitution to the so-called "Fuhrerprinzip" (leader principle). The
      outbreak of war in 1939 lead to a further cesura in the activities of the
      society, which were impeded by personal and material deficiencies and were ceased
      in 1945 due to the war.

PMID- 20821223
TI  - Changes in key hypothalamic neuropeptide populations in Huntington disease
      revealed by neuropathological analyses.
AB  - Huntington disease (HD) is a fatal neurodegenerative disorder caused by expansion
      of a CAG repeat in the HD gene. Degeneration concentrating in the basal ganglia
      has been thought to account for the characteristic psychiatric symptoms,
      cognitive decline and motor dysfunction. However, the homeostatic control of
      emotions and metabolism are disturbed early in HD, and focused studies have
      identified a loss of orexin (hypocretin) neurons in the lateral hypothalamus in
      HD patients. There has been limited assessment of other hypothalamic cell
      populations that may be involved. In this study, we quantified the neuropeptide
      expressing hypothalamic neurons known to regulate metabolism and emotion in
      patients with HD compared to healthy controls using unbiased stereological
      methods. We confirmed the loss of orexin-expressing neurons in HD and revealed
      substantial differences in the peptide expression of other neuronal populations
      in the same patients. Both oxytocin- and vasopressin-expressing neurons were
      decreased by 45 and 24%, respectively, while the number of cocaine- and
      amphetamine-regulated transcript (CART)-expressing neurons was increased by 30%.
      The increased expression of CART in the hypothalamus is consistent with a
      previous study showing increased CART levels in cerebrospinal fluid from HD
      patients. There was no difference in the numbers of neuropeptide Y-expressing
      neurons. These results show significant and specific alterations in the peptide
      expression of hypothalamic neurons known to regulate metabolism and emotion. They
      may be important in the development of psychiatric symptoms and metabolic
      disturbances in HD, and may provide potential targets for therapeutic
      interventions.

PMID- 20821224
TI  - Hematoxylin-stainability of keratohyalin granules is due to the novel component,
      fibrinogen gamma-chain protein.
AB  - Hematoxylin-stainability of keratohyalin granules (KHG) using biochemical and
      immunohistochemical techniques is due to the presence of a fibrinogen gamma-chain
      protein. A protein with a molecular weight of 100 kDa was stained with anti-Ted-H
      1 monoclonal antibody and hematoxylin solution (hematoxylin-stainable protein).
      Since the amino acid sequence of the hematoxylin-stainable protein was to that of
      fibrinogen gamma-chain protein, a peptide was synthesized and an antibody against
      the peptide was produced. This antibody reacted with the hematoxylin-stainable
      protein and fibrinogen gamma-chain protein on immunoblot analysis and with KHG on
      immunohistochemical examination. Furthermore, a commercial anti-fibrinogen gamma
      chain protein antibody (Ab) also reacted with the hematoxylin-stainable protein
      as well as fibrinogen. In contrast, anti-fibrinogen beta-chain protein Ab did not
      react with the hematoxylin-stainable protein. The fibrinogen gamma-chain protein
      also stained with hematoxylin. These findings suggested that fibrinogen gamma
      chain protein may be a novel component protein of KHG and may induce the
      hematoxylin-stainability of KHG.

PMID- 20821225
TI  - The impact of previous cesarean section on the success of future fetal
      programming pattern.
AB  - PURPOSE: The purpose of this study is to examine whether cesarean section in the
      first pregnancy is associated with the success or failure of programmed fetal
      growth phenotypes or patterns in the subsequent pregnancy. METHODS: We analyzed
      data from a population-based retrospective cohort of singleton deliveries that
      occurred in the state of Missouri from 1978 to 2005 (n = 1,224,133). The main
      outcome was neonatal mortality, which was used as an index of the success of
      fetal programming. Cox proportional hazard and logistic regression models were
      used to generate point estimates and 95% confidence intervals. RESULTS: Mothers
      delivering by cesarean section in the first pregnancy were less likely to deliver
      subsequent appropriate-for-gestational-age (AGA) neonates (OR 0.91, 95% CI 0.89
      0.92) when compared with mothers delivering vaginally. Of the 1,457 neonatal
      deaths in the second pregnancy, 383 early neonatal and 95 late neonatal deaths
      were to mothers with cesarean section deliveries in the first pregnancy. When
      compared with women with a previous vaginal delivery, AGA neonates of women with
      a primary cesarean section had 20% increased risk of both neonatal (OR 1.20, 95%
      CI 1.05-1.37) and early neonatal (OR 1.23, 95% CI 1.05-1.43) death. CONCLUSION:
      Our study suggests that previous cesarean section is a risk factor for neonatal
      mortality among AGA infants of subsequent pregnancy. Future prospective studies
      are needed to confirm these findings.

PMID- 20821226
TI  - A systematic review: endometriosis presenting with ascites.
AB  - BACKGROUND: The present review aims to increase the awareness of the
      gynecologists by analyzing all the case reports which refer to endometriosis
      presenting either with only ascites or with massive ascites with pleural
      effusion. METHODS: To conduct the present review, the CENTRAL (in the Cochrane
      Library, current issue), MEDLINE (Silver Platter, from 1950 to 2010), and EMBASE
      (from 1950 to 2010) electronic databases were searched. As a result, all the
      publications based on the keywords relating to the review topic were acquired.
      RESULTS: Since the description of first case in 1954, endometriosis-related
      ascites was reported to occur in a total of 63 women who were aged between 19 and
      51 years. Approximately 63.0% of the recruited women for whom ethnicity was
      specified were of African origin (29 out of 46). Of the 50 subjects with known
      obstetric history, 41 (82.0%) were nulliparous. Abdominal distention,
      anorexia/weight loss, abdominal pain, and menometrorrhagia were the most
      frequently encountered clinical symptoms, whereas pelvic mass was the most common
      physical finding. The serum concentrations of CA 125 were between 20 and 3,504
      IU/ml for 19 women whose CA 125 levels were determined. Pleural effusion was also
      present in 38.1% of the reviewed subjects (24 out of 63). The clinical features
      of the women with endometriosis-related ascites and pleural effusion were similar
      to those of the women who had only endometriosis-related ascites. CONCLUSION:
      Endometriosis-related ascites and/or pleural effusion refers to extensive disease
      with a high risk for recurrence which usually affects non-Caucasian, nulliparous
      women of reproductive age and leads to clinical symptoms resembling those of an
      ovarian malignancy. Therefore, clinicians should consider endometriosis in
      differential diagnosis of pelvic masses and also include endometriosis in
      diagnostic workup of ascites or pleural effusion.

PMID- 20821227
TI  - The effects of different lignans and isoflavones, tested as aglycones and
      glycosides, on hormone receptor-positive and -negative breast carcinoma cells in
      vitro.
AB  - PURPOSE: Phytooestrogens are known to cause anti-cancer effects on mamma
      carcinoma cells. In this study, the effects of the lignan secoisolariciresinol
      and the isoflavone glycosides and aglycones genistein, genistin, daidzein and
      daidzin were tested on MCF-7 and BT20 cells in vitro. METHODS: First, the
      cellular expression of hormone receptors was examined by immunohistochemical
      procedures. The effects of the phytooestrogens on the cells were detected by
      using three different assays measuring cell letality, viability and
      proliferation. The phytooestrogens were tested in concentrations of 1, 5, 10 and
      50 MUg/mL, respectively. 17beta-oestradiol and tamoxifen were used as controls,
      respectively, in the same concentrations as the phytooestrogens. RESULTS: The
      immunohistochemistry showed evidence of oestrogen- and progesterone receptors at
      the MCF-7 cell line, whereas no expression could be seen at the BT20 cells. Among
      the phytooestrogens, genistein and secoisolariciresinol showed various anti
      cancerogenic effects on both cell lines, respectively, but only in the highest
      concentration. Regarding the controls, tamoxifen showed a stronger antivital and
      anti-proliferative effect on BT20 than on MCF-7. Oestradiol caused sporadic anti
      cancer effects on both cell lines, respectively, at its highest concentration.
      CONCLUSIONS: Genistein and Secoisolariciresinol have anti-cancer properties on
      MCF-7 and BT20 in vitro. There are differences in the effects of isoflavones
      depending on the glycolysation status. The role of the oestrogen receptors in the
      mechanisms of action of both the phytooestrogens and controls is of less
      importance. Further investigations have to be carried out, especially concerning
      the mechanisms of action. Phytooestrogens may be potential substances in the
      therapy of mamma carcinomas.

PMID- 20821228
TI  - Fibrin-glue assisted multilayered amniotic membrane transplantation in surgical
      management of pediatric corneal limbal dermoid: a novel approach.
AB  - PURPOSE: To report a new surgical technique for excising pediatric corneal limbal
      dermoid and the post-resection ocular surface reconstruction. METHODS: We
      describe a method of deep lamellar excision followed by sutureless multilayered
      amniotic membrane transplantation in surgical management of corneal limbal
      dermoid. RESULT: This technique achieves a rapid corneal re-epithelization,
      reduces post-operative pain, and will diminish post-operative scarring.
      Preoperative corneal astigmatism will persist. CONCLUSION: This method offers an
      alternative surgical approach in comparison to simple excision in removal of
      simple pediatric corneal limbal dermoids.

PMID- 20821229
TI  - Simvastatin suppresses expression of angiogenic factors in the retinas of rats
      with streptozotocin-induced diabetes.
AB  - BACKGROUND: Angiogenic factors such as vascular endothelial growth factor (VEGF),
      erythropoietin, and angiopoietin play important roles in the pathophysiology of
      diabetic retinopathy. Increased amounts of reactive oxygen species (ROS) are also
      known to associated with diabetic retinopathy and VEGF expression. This study
      evaluated the effect of a simvastatin on ROS generation and the changes in
      various angiogenic factors in the retinas of diabetic rats. METHODS: The rats
      were divided into normal, diabetes mellitus (DM), and simvastatin-treated groups
      (each group, n = 10). Diabetes was induced by intraperitoneal injection of
      streptozotocin into 20 Sprague-Dawley rats. After diabetic induction, simvastatin
      (5mg/kg) was administered orally to ten rats. The expression levels of VEGF,
      erythropoietin, angiopoietin 1 and 2, and NADPH oxidase were examined in rat
      retinas by RT-PCR and Western blot. Superoxide formation was examined by
      dihydroethidium (DHE) staining. RESULTS: DHE analysis revealed increased
      superoxide formation in the retinas of the diabetic group, which was decreased in
      the group treated with simvastatin. Western blot analysis showed that NADPH
      oxidase levels were decreased in the diabetic group and remained normal in the
      simvastatin-treated group. Simvastatin treatment blocked hyperglycemia-induced
      increases in VEGF, angiopoietin 2 and erythropoietin levels, as demonstrated by
      RT-PCR and Western blot analysis. CONCLUSIONS: Simvastatin treatment led to
      suppression of superoxide formation and decreased expression of VEGF,
      angiopoietin 2 and erythropoietin in diabetic rat retinas.

PMID- 20821230
TI  - Expression of SHH signaling pathway components in the developing human lung.
AB  - The Sonic hedgehog (Shh) cascade is crucial for the patterning of the early lung
      morphogenesis in mice, but its role in the developing human lung remains to be
      determined. In the present study, the expression patterns of SHH signaling
      pathway components, including SHH, PTCH1, SMO, GLI1, GLI2 and GLI3 were examined
      by in situ hybridization and immunohistochemistry, and compared with the
      equivalent patterns in mice. Our results showed that, as in mice, SHH was
      expressed in the epithelium of the developing human lung. However, SHH receptors
      (PTCH1 and SMO) and SHH signaling effectors (GLI1-3) were strongly detected in
      the human lung epithelium, but weakly in the mesenchyme, slightly different from
      their expressions in mice. Furthermore, the expression levels of SHH signaling
      pathway genes in human lung, but not that of GLI1, were subsequently
      downregulated at the canalicular stage evaluated by real-time PCR, coincident
      with a decline in the developing murine lung. In conclusion, in spite of slight
      differences, the considerable similarities of gene expression in human and mice
      suggest that conserved molecular networks regulate mammalian lung development.

PMID- 20821231
TI  - Cyclin D3 gene amplification in bladder carcinoma in situ.
AB  - Carcinoma in situ (CIS) is a non-papillary high-grade, potentially aggressive,
      and unpredictable manifestation of bladder urothelial carcinoma. The aim of this
      study was to assess patterns of Cyclin D3 gene amplification in Bacillus Calmette
      Guerin (BCG)-treated CIS and correlate gene status with recurrence-free and
      progression-free survival. A sequential cohort series of 28 primary (isolated) or
      secondary (concomitant) bladder CIS samples in which there was enough tissue
      material to assess Cyclin D3 gene status by fluorescent in situ hybridization was
      the study group. Cyclin D3 gene amplification was present in 29% of secondary
      CIS; none of primary CIS samples had Cyclin D3 gene amplification. Cyclin D3
      amplification was related to recurrence- (p = 0.046) and progression-free
      survival (p = 0.002). Type of bladder CIS (primary vs. secondary) was unrelated
      to recurrence- or progression-free survival in the current series. Cox's
      regression analysis selected Cyclin D3 as an independent predictor of progression
      free survival (p = 0.041, relative risk = 61.503, 95% confidence interval = 1.1
      274.710). None of primary CIS cases recurred on follow-up; nine secondary CIS
      recurred and four of them progressed to invasive bladder carcinoma HG T1 (n = 1),
      T2b N0M0 (n = 1), T3b N1M0 (n = 1) and T4aN1M1 (n = 1). Mean recurrence +/- SD
      (months) occurred at 19.5 +/- 2.06 (95% (confidence interval (CI)), 15.5-23.6);
      mean progression (months) occurred at 23.8 +/- 1.46 (95% (CI), 20.9-26.7). Our
      study suggests that Cyclin D3 gene amplification might be a predictor of
      aggressiveness in BCG-treated CIS.

PMID- 20821232
TI  - Effect of inhibitors of arachidonic acid metabolism on prostaglandin E2
      production by Candida albicans and Candida dubliniensis biofilms.
AB  - Arachidonic acid (AA) is released from infected host cells during Candida
      albicans infection and may serve as carbon source for yeast growth and as
      precursor for the production of biologically active eicosanoids, such as
      prostaglandin E2 (PGE2) by C. albicans. However, the mechanism involved in this
      production is still unclear. Therefore, it was of interest to investigate the
      effect of different arachidonic acid metabolism inhibitors on PGE2 production by
      biofilms of C. albicans and the closely related C. dubliniensis. This was done by
      growing Candida biofilms in the presence of AA as well as cytochrome P450 (CYP),
      multicopper oxidase, cyclooxygenase or lipoxygenase inhibitors. The concentration
      of PGE2 was determined by a monoclonal PGE2 enzyme-linked immunosorbent assay and
      verified with LCMS/MS. The results obtained indicate the ability of C. albicans
      and C. dubliniensis biofilms to produce PGE2 from exogenous AA. The use of
      different inhibitors suggested that CYPs and multicopper oxidases are involved in
      PGE2 production by these Candida biofilms.

PMID- 20821233
TI  - Indirect effect of a turmeric diet: enhanced bile duct proliferation in Syrian
      hamsters with a combination of partial obstruction by Opisthorchis viverrini
      infection and inflammation by N-nitrosodimethylamine administration.
AB  - The present study revealed the indirect effect of a turmeric (TUR) diet on the
      histopathological changes and proliferating cell nuclear antigen staining in
      Syrian hamsters with partial obstruction by liver fluke (Opisthorchis viverrini)
      infection and inflammation by N-nitrosodimethylamine (NDMA) administration. The
      result of the analysis of histopathological changes shows that a TUR diet has an
      anti-inflammatory property in the case of a single condition of NDMA
      administration or O. viverrini infection, as has been reported previously.
      Unfortunately, an adverse indirect effect of TUR was observed in the combination
      of infection with O. viverrini and administration of NDMA, with a 30-50% increase
      in new bile duct formation, correlated with an increase in proliferating cell
      nuclear antigen. Our present result suggests that the properties of curcumin are
      anti-inflammation and antioxidant including enhancing biliary contraction and
      bile flow. Thus, a combination of factors (treated with O. viverrini, NDMA, and
      TUR diet) result in an increasing bile duct proliferation which may cause from
      biliary homeostasis.

PMID- 20821234
TI  - [Patients with chronic pain syndromes. Impact of an individual outpatient therapy
      program on pain and health-related quality of life].
AB  - BACKGROUND: The study was performed to reveal the effect of an individualized
      personal outpatient therapy program, based on a multidisciplinary assessment, on
      pain and health-related quality of life in patients with chronic pain. METHODS:
      Fifty patients were prospectively evaluated before and 3 months after
      establishment of an individualized outpatient therapy program. Health-related
      quality of life, pain and pain-related disability, depression and motivation to
      adopt self-management of chronic pain were assessed. Therapy adherence was tested
      with a structured interview. RESULTS: Only marginal improvements were observed in
      terms of pain and health-related quality of life. Therapy adherence varied
      between the different therapies. CONCLUSIONS: An individualized personal
      outpatient therapy program has only marginal effects on pain and health-related
      quality of life in patients with chronic pain.

PMID- 20821235
TI  - Small bile duct involvement in IgG4-related sclerosing cholangitis: liver biopsy
      and cholangiography correlation.
AB  - BACKGROUND: IgG4-related sclerosing cholangitis (IgG4-SC) needs to be
      differentiated from primary sclerosing cholangitis (PSC). In this study, we
      performed a retrospective study to reveal cases in which liver needle biopsy was
      useful for differential diagnosis. METHODS: Nineteen patients with IgG4-SC and 22
      patients with PSC were studied. All patients underwent endoscopic retrograde
      cholangiography and liver needle biopsy. We defined small bile duct involvement
      of IgG4-SC histologically as damage to the small bile duct associated with
      infiltration of >=10 IgG4+ plasma cells per high power field (HPF).
      Clinicopathological characteristics were compared between IgG4-SC patients with
      and without small bile duct involvement. RESULTS: Small bile duct involvement was
      observed in 5 (26%) of the patients with IgG4-SC. Patients with small bile duct
      involvement showed a higher incidence of intrahepatic biliary strictures on
      cholangiography (80 vs. 21%, p = 0.038). Conversely, 4 of 7 (57%) patients with
      intrahepatic biliary strictures on cholangiography had histologically evident
      small duct involvement. The number of IgG4+ plasma cells was significantly
      correlated with the site of the most proximal stricture on cholangiograms (p =
      0.021). The number of IgG4+ plasma cells per HPF was significantly higher in IgG4
      SC patients with intrahepatic biliary strictures than in those with PSC (13.4 vs.
      0.4 cells/HPF, p < 0.001). CONCLUSIONS: Involvement of small bile ducts is more
      frequent in patients with intrahepatic biliary strictures on cholangiography, and
      liver needle biopsy is especially useful for these patients.

PMID- 20821236
TI  - Clinicopathological features of severe and fulminant forms of autoimmune
      hepatitis.
AB  - BACKGROUND AND AIMS: Diagnosis of the acute presentation of autoimmune hepatitis
      (AIH) is difficult because patients do not always show typical
      clinicopathological features of AIH. Although some of them progress to fulminant
      hepatitis, the survival rate of which is <20% without liver transplantation,
      their clinicopathological features have remained uncertain. We examined them for
      a better understanding and improvement of the prognosis of "life-threatening"
      severe and fulminant AIH. METHODS: Clinical, biochemical and pathological
      features of 28 patients with severe or fulminant AIH and treatment responses were
      examined retrospectively. RESULTS: At the time of admission, mean immunoglobulin
      G was 2479 +/- 1170 mg/dl, with 7 (25%) patients showing normal levels. Anti
      nuclear antibody was <= 1:40 in 8 (29%). Liver histology showed severe activity
      in 95% and acute hepatitis in 86% of the patients. Centrilobular necrosis
      including submassive and massive necrosis was characteristic. Of the 25 patients
      treated with corticosteroids, 17 responded and 8 did not. Responders to
      corticosteroids showed younger age and higher prothrombin time (PT) activity than
      non-responders at the time of corticosteroid administration. The improvement of
      PT activity during 2 weeks and 4 weeks and total bilirubin level during 4 weeks
      was statistically significant in responders, but not in non-responders.
      CONCLUSIONS: We should diagnose and treat acute onset AIH patients before they
      develop into severe and fulminant disease. Performing liver biopsy at the early
      stage of acute onset AIH, evaluating the biopsy specimens precisely and
      initiating corticosteroid therapy may be essential for improving the prognosis
      without liver transplantation.

PMID- 20821237
TI  - Evaluation of RAPID((r)) 5 Access software for examination of capsule endoscopies
      and reading of the capsule by an endoscopy nurse.
AB  - BACKGROUND: Since capsule endoscopy (CE) is time consuming, one possible cost
      effective strategy could be the use of an expert endoscopic assistant and
      available software to select images. Aims were to examine the clinical utility of
      RAPID((r)) 5 Access software and find the optimum setting mode for reading. We
      also evaluated whether a nurse could preview the CE video and detect significant
      lesions accurately. METHODS: The capsule images in 14 volunteers with known
      mucosal injury induced by low dose aspirin and in 30 patients who were known to
      have a variety of significant lesions were selected. Using three setting modes of
      RAPID((r)) 5 Access software, the detection rate and reading time for CE images
      by two well-trained physicians and one expert nurse were compared. RESULTS: There
      was no significant difference in detection rate among the three readers. The
      detection rate using Quickview RAPID((r)) 5 Access was significantly higher than
      that using RAPID((r)) Reader version 4.1. Comparison among the three modes of
      RAPID((r)) 5 Access showed that auto mode as well as displaying a single image at
      12 fps was superior in the detection rate of denuded redness, while its reading
      time was longer compared to the other modes. Some significant lesions were not
      detected by using Quickview and Quadview modes. CONCLUSIONS: RAPID((r)) 5 Access
      improves diagnostic yield, reducing reading time; however, it is still
      unacceptable because of the diagnostic miss rate and may be useful as an
      ancillary reading tool. Developing further improved software and training expert
      assistants for reading capsule images are necessary.

PMID- 20821238
TI  - Evaluation of efficacy and safety of fentanyl transdermal patch (Durogesic D
      TRANS) in chronic pain.
AB  - PURPOSE: Opioids are used in controlling several types of pain. This study was
      designed to evaluate the efficacy and safety of the fentanyl transdermal patch
      type system (Durogesic(r) D-TRANS). METHODS: Patients who complained of chronic
      moderate to severe pain were enrolled. Administration dosages of fentanyl patch
      started from 12.5 MUg/h and could be increased by 12.5 MUg/h or 25 MUg/h, if the
      average pain score of 4 or higher occurred within 72 h. The total administration
      period was 12 weeks. The type, location, characteristics, and duration of pain
      were evaluated. Also, on day 0, weeks of 4, 8, and 12, the physician's assessment
      of pain intensity, the patient's assessment of pain intensity, the assessment of
      impact of pain on functions, and the assessment of the impact of pain on sleep
      were assessed. In addition, side effects were evaluated during the study
      duration. RESULTS: A total of 65 cases were enrolled, and the final evaluated
      cases were 41. Before treatment, the average physician's assessment of pain
      intensity was 6.70 +/- 1.41, and the average patient's assessment of pain
      intensity was 7.02 +/- 1.63. In the final visit, the average physician's
      assessment of pain intensity was 2.58 +/- 1.72, and the average patient's
      assessment of pain intensity was 2.86 +/- 1.78. CONCLUSIONS: This prospective
      study shows that the fentanyl patch is effective in alleviating moderate to
      severe chronic noncancer pain including neuropathic pain down to mild pain.
      Therefore, the fentanyl patch should be considered before other invasive
      intervention procedures in chronic moderate to severe noncancer pain.

PMID- 20821239
TI  - ESM-1 silencing decreased cell survival, migration, and invasion and modulated
      cell cycle progression in hepatocellular carcinoma.
AB  - Endothelial cell-specific molecule-1 (ESM-1) is a secretory proteoglycan
      comprising a mature polypeptide of 165 amino acids and a single dermatan sulfate.
      The aim of this study was to evaluate endothelial cell-specific molecule-1 (ESM
      1) as a hepatocellular carcinoma (HCC) marker and to analyze the effect of ESM-1
      gene silencing in hepatocellular carcinoma cells. RT-PCR and Western Blot
      analysis revealed overexpression of ESM-1 in human HCC liver tissue and in serum
      from patients with HCC. Sandwich ELISA assay was used for quantitative analysis
      of ESM-1 in serum. Levels of ESM-1 were significantly elevated in the serum of
      patients with HCC (n = 40) as compared to serum from patients with hepatitis (AH,
      n = 40; CH, n = 39) or liver cirrhosis (n = 40) or from healthy subjects (n =
      40). The accuracy of ESM-1 for HCC was higher than that of alpha-fetoprotein
      (AFP) according to ROC curve analysis. Expression of ESM-1 siRNA decreased cell
      survival through the inhibition of NF-kappaB pathway and induced cell cycle
      arrest by PTEN induction resulting in the inhibition of cyclin D1 in SK-Hep1
      cells. Furthermore, ESM-1 silencing inhibited cell migration and invasion of SK
      Hep1 cells. This study demonstrates that ESM-1 as a potential tumor marker is
      overexpressed in most tissues and serum in the presence of HCC and is involved
      with cell survival, cell cycle progression, migration, and invasion of
      hepatocellular carcinoma cells. Based on our results, we suggest that ESM-1 or a
      combination of ESM-1 and AFP is useful markers for diagnosis of HCC and ESM-1 may
      be useful therapeutic target of hepatocellular carcinoma.

PMID- 20821240
TI  - Crystal structure of the zinc-, cobalt-, and iron-containing adenylate kinase
      from Desulfovibrio gigas: a novel metal-containing adenylate kinase from Gram
      negative bacteria.
AB  - Adenylate kinases (AK) from Gram-negative bacteria are generally devoid of metal
      ions in their LID domain. However, three metal ions, zinc, cobalt, and iron, have
      been found in AK from Gram-negative bacteria. Crystal structures of substrate
      free AK from Desulfovibrio gigas with three different metal ions (Zn(2+), Zn-AK;
      Co(2+), Co-AK; and Fe(2+), Fe-AK) bound in its LID domain have been determined by
      X-ray crystallography to resolutions 1.8, 2.0, and 3.0 A, respectively. The zinc
      and iron forms of the enzyme were crystallized in space group I222, whereas the
      cobalt-form crystals were C2. The presence of the metals was confirmed by
      calculation of anomalous difference maps and by X-ray fluorescence scans. The
      work presented here is the first report of a structure of a metal-containing AK
      from a Gram-negative bacterium. The native enzyme was crystallized, and only zinc
      was detected in the LID domain. Co-AK and Fe-AK were obtained by overexpressing
      the protein in Escherichia coli. Zn-AK and Fe-AK crystallized as monomers in the
      asymmetric unit, whereas Co-AK crystallized as a dimer. Nevertheless, all three
      crystal structures are very similar to each other, with the same LID domain
      topology, the only change being the presence of the different metal atoms. In the
      absence of any substrate, the LID domain of all holoforms of AK was present in a
      fully open conformational state. Normal mode analysis was performed to predict
      fluctuations of the LID domain along the catalytic pathway.

PMID- 20821241
TI  - Structure of anticancer ruthenium half-sandwich complex bound to glycogen
      synthase kinase 3beta.
AB  - The 3.15-A-resolution crystal structure of the R enantiomer of the highly
      bioactive and antiproliferative half-sandwich ruthenium complex DW12 bound to the
      ATP binding site of glycogen synthase kinase 3beta (GSK-3beta) is reported and
      the binding is compared with the GSK-3beta binding of staurosporine and other
      organic inhibitors. The structure reveals a close packing of the organometallic
      inhibitor in the ATP binding site of GSK-3beta via an induced-fit mechanism. The
      molecular structure of (R)-DW12 with the CO ligand oriented perpendicular to the
      pyridocarbazole heterocycle allows the complex to stretch the whole distance
      sandwiched between the faces of the N- and C-terminal lobes and to interact
      tightly with the flexible glycine-rich loop, which is uncommon for the
      interaction of GSK-3beta with organic inhibitors.

PMID- 20821242
TI  - Musculoskeletal damage: what is the difference in children? Pain in the forearm
      due to a fall.

PMID- 20821244
TI  - Permeability of dura mater: a possible link between cortical spreading depression
      and migraine pain? A comment.
AB  - In the wake of cortical spreading depression (CSD) it has been suggested that
      noxious substances diffuse through the dura with resulting firing of epidural
      nerves. In my view this is unlikely because there are good reasons to suggest
      that there must be a dura-brain barrier. Alternatively collateral branches from
      the trigeminal nerve to the pia and the dura may signal what is happening with
      ions and substances on the brain surface during CSD to the epidural space.

PMID- 20821245
TI  - Strain-based estimation of time-dependent transmural myocardial architecture in
      the ovine heart.
AB  - Left ventricular myofibers are connected by an extensive extracellular collagen
      matrix to form myolaminar sheets. Histological cardiac tissue studies have
      previously observed a pleated transmural distribution of sheets in the ovine
      heart, alternating sign of the sheet angle from epicardium to endocardium. The
      present study investigated temporal variations in myocardial fiber and sheet
      architecture during the cardiac cycle. End-diastolic histological measurements
      made at subepicardium, midwall, and subendocardium at an anterior-basal and a
      lateral-equatorial region of the ovine heart, combined with transmural myocardial
      Lagrangian strains, showed that the sheet angle but not the fiber angle varied
      temporally throughout the cardiac cycle. The magnitude of the sheet angle
      decreased during systole at all transmural depths at the anterior-basal site and
      at midwall and subendocardium depths at the lateral-equatorial site, making the
      sheets more parallel to the radial axis. These results support a previously
      suggested accordion-like wall-thickening mechanism of the myocardial sheets.

PMID- 20821247
TI  - Optimization of enantioselective synthesis of methyl (R)-2-chloromandelate by
      whole cells of Saccharomyces cerevisiae.
AB  - Methyl (R)-2-chloromandelate, a key intermediate in the synthesis of clopidogrel,
      was obtained by the reduction of methyl-2-chlorobenzoylformate using whole cells
      of Saccharomyces cerevisiae. A 100% conversion and 96.1% of enantiomeric excess
      (ee) value was obtained when 17 methyl-2-chlorobenzoylformate/l was reacted with
      8 g S. cerevisiae/l and 83 g glucose/l at pH 7.

PMID- 20821243
TI  - Modulation of transcription factor and metabolic pathway genes in response to
      water-deficit stress in rice.
AB  - Water-deficit stress is detrimental for rice growth, development, and yield.
      Transcriptome analysis of 1-week-old rice (Oryza sativa L. var. IR64) seedling
      under water-deficit stress condition using Affymetrix 57 K GeneChip(r) has
      revealed 1,563 and 1,746 genes to be up- and downregulated, respectively. In an
      effort to amalgamate data across laboratories, we identified 5,611 differentially
      expressing genes under varying extrinsic water-deficit stress conditions in six
      vegetative and one reproductive stage of development in rice. Transcription
      factors (TFs) involved in ABA-dependent and ABA-independent pathways have been
      found to be upregulated during water-deficit stress. Members of zinc-finger TFs
      namely, C2H2, C2C2, C3H, LIM, PHD, WRKY, ZF-HD, and ZIM, along with TF families
      like GeBP, jumonji, MBF1 and ULT express differentially under water-deficit
      conditions. NAC (NAM, ATAF and CUC) TF family emerges to be a potential key
      regulator of multiple abiotic stresses. Among the 12 TF genes that are co
      upregulated under water-deficit, salt and cold stress conditions, five belong to
      the NAC TF family. We identified water-deficit stress-responsive genes encoding
      key enzymes involved in biosynthesis of osmoprotectants like polyols and sugars;
      amino acid and quaternary ammonium compounds; cell wall loosening and structural
      components; cholesterol and very long chain fatty acid; cytokinin and secondary
      metabolites. Comparison of genes responsive to water-deficit stress conditions
      with genes preferentially expressed during panicle and seed development revealed
      a significant overlap of transcriptome alteration and pathways.

PMID- 20821246
TI  - Gene delivery of soluble vascular endothelial growth factor receptor-1 (sFlt-1)
      inhibits intra-plaque angiogenesis and suppresses development of atherosclerotic
      plaque.
AB  - Intra-plaque angiogenesis plays an important role in the development of
      atherosclerotic plaque. Vascular endothelial growth factor (VEGF) is a major
      initiating factor in this pathologic progress. One selective and specific
      inhibitor of VEGF is soluble VEGF receptor-1 (sFlt-1). The anti-angiogenic
      utilization of sFlt-1 in treatment of atherosclerotic plaque has not been fully
      confirmed yet. Our study was designed to construct eukaryotic expression
      recombinant pEGFP-N1-sFlt-1, evaluate sFlt-1 recombinant's effects on endothelial
      cells proliferation and tube formation in vitro, and investigate effects of local
      high-expressed sFlt-1 on atherosclerotic plaque in vivo. Rabbit models of
      atherosclerotic plaque were established by high-lipid diet combined with injury
      induced by balloon catheter on iliac artery intima. Animals were divided into
      four groups randomly: control group (C), atherosclerotic plaque group (AP),
      atherosclerotic plaque with blank vector pEGFP-N1 transfection group (APV), and
      atherosclerotic plaque with pEGFP-N1-sFlt-1 transfection group (APsFlt-1). The
      local expression of sFlt-1 protein in target artery was detected by western
      blotting. The plaque area (PA), plaque circumference (PC), and maximum plaque
      thickness (MPT) were measured via HE staining. Degree of intra-plaque
      angiogenesis was evaluated by CD34+ cells immunohistochemistry. As results, we
      observed that pEGFP-N1-sFlt-1 transfection suppressed the HUVECs proliferation
      and ability of tube formation, against the effect of VEGF. We obtained higher
      local expression of sFlt-1 protein in Group APsFlt-1 than that in other groups (P
      < 0.05). PA, PC, and MPT of plaque in group APsFlt-1 were significantly decreased
      when compared with other groups (P < 0.05). Amount of annulations surrounded by
      CD34-positive cells was significantly decreased in pEGFP-N1-sFlt-1 transfection
      group, which represented decreased level of intra-plaque neovessels formation.
      The present study confirmed that local gene delivery of sFlt-1 can suppress
      plaque formation, as one of possible mechanisms, via inhibitive effect on intra
      atherosclerotic plaque angiogenesis, which hints at the clinical utility of sFlt
      1 in atherosclerosis therapy.

PMID- 20821248
TI  - Autoinduction of a genetic locus encoding putative acyltransferase in
      Corynebacterium glutamicum.
AB  - A genetic locus, encoding putative acyltransferase, was induced by autoinducers
      in Corynebacterium glutamicum. The autoinducers were maximally produced by the
      bacterium after 24 h culture. Those molecules are resistant to proteinase K
      treatment (300 MUg ml(-1)) for 30 min at 37 degrees C or at 121 degrees C for 15
      min, and remained stable after extensive storage at 4 degrees C. Autoinducers in
      the cell-free culture fluids from Corynebacterium ammoniagenes and Pseudomonas
      aeruginosa also induced the expression of acyltransferase in C. glutamicum,
      suggesting possible cross-recognition of the autoinducers by C. glutamicum. C.
      glutamicum thus possesses an autoinduction system which secretes autoinducers
      during growth, triggering the expression of downstream genes, exemplified by the
      putative acyltransferase gene.

PMID- 20821249
TI  - Novel bacterial ferulic acid esterase from Cellvibrio japonicus and its
      application in ferulic acid release and xylan hydrolysis.
AB  - Recent genome sequencing of Cellvibrio japonicas revealed the presence of two
      highly homologous ferulic acid esterases (FAEs), encoded by fee1A and fee1B. In
      this work, the putative FAE, Fee1B, was successfully cloned and expressed in an
      E. coli system and the purified enzyme was characterized as a type-D FAE with a
      pH and temperature optima of 6.5 and 35-40 degrees C, respectively. Additionally,
      the two tandem N-terminal carbohydrate binding modules of the multi-domain enzyme
      were shown to be crucial for optimum enzyme activity. The potential of the enzyme
      in biomass processing was demonstrated with its high synergy with a xylanase in
      the release of reducing sugar from arabinoxylan and its ability to liberate
      ferulic acid from various complex xylan substrates.

PMID- 20821250
TI  - High-level expression and improved folding of proteins by using the vp39 late
      promoter enhanced with homologous DNA regions.
AB  - Some recombinant proteins expressed by baculovirus expression vector systems
      (BEVS) aggregate because the BEVS can produce large amounts of protein late
      during infection, when post-translational modification and protein quality
      control mechanisms are inactive. For expression during earlier stages than that
      driven by the polyhedrin (polh) very late promoter, transfer vectors were
      generated in which this promoter was replaced with a green fluorescent protein
      (GFP) gene controlled by a vp39 late promoter modified to contain HR3, one of the
      homologous DNA regions (HRs) of Bombyx mori nuclear polyhedrosis virus (BmNPV).
      The rise times of the fluorescence of GFP expressed by using recombinant viruses
      carrying the modified vp39 promoter were earlier than those associated with
      either the polh promoter or the native vp39 promoter lacking HR3. In transient
      expression assays, the vp39 late promoter in transfer vectors behaved like a
      delayed-early promoter, and was enhanced by HR3, and required IE-1 protein and
      various viral gene products encoded on both sides of BmNPV polh. When the vp39
      promoter with HR3 was used, the aggregation of several foreign proteins expressed
      by the BEVS was markedly decreased. This study provides a new option for the
      expression of sufficiently quality-controlled proteins by using the vp39 promoter
      and HR3 in BEVS early in baculovirus infection, when the infection has caused
      little damage in the host cells.

PMID- 20821251
TI  - DNA repair pathways and their implication in cancer treatment.
AB  - Many cytotoxic agents used in cancer treatment exert their effects through their
      ability to directly or indirectly damage DNA and thus resulting in cell death.
      Major types of DNA damage induced by anticancer treatment include strand breaks
      (double or single strand), crosslinks (inter-strand, intra-strand, DNA-protein
      crosslinks), and interference with nucleotide metabolism and DNA synthesis. On
      the other hand, cancer cells activate various DNA repair pathways and repair DNA
      damages induced by cytotoxic drugs. The purpose of the current review is to
      present the major types of DNA damage induced by cytotoxic agents, DNA repair
      pathways, and their role as predictive agents, as well as evaluate the future
      perspectives of the novel DNA repair pathways inhibitors in cancer therapeutics.

PMID- 20821252
TI  - DNA methylation or histone modification status in metastasis and angiogenesis
      related genes: a new hypothesis on usage of DNMT inhibitors and S
      adenosylmethionine for genome stability.
AB  - Metastasis is a leading cause of mortality and morbidity in cancer. This process
      needs angiogenesis. The biology underlying cancer, metastasis, and angiogenesis
      has been investigated so as to determine the therapeutic targets. Invasive and
      metastatic cancer cells have undergone numerous genetic and epigenetic changes,
      manifested by cytoskeletal changes, loss of adhesion, and expression of
      proteolytic enzymes that degrade the basement membrane. Additionally, in
      endothelial cells, some epigenetic modifications occur during the formation of
      angiogenesis. Researchers have used some methylation inhibitors, histone
      deacetylase inhibitors, or methylating agents (such as S-adenosylmethionine, SAM)
      against cancer and angiogenesis. Although they are effective to beat these
      diseases, each one results in differentiation or changes in genome structure. We
      review epigenetically modified genes related with angiogenesis and metastasis in
      cancer and endothelial cells, and suggest a new proposal. This hypothesis has
      discussed the importance of the usage of DNA methylation inhibitors together with
      SAM to prevent tumor progression and genome instability or changes resulting in
      additional diseases.

PMID- 20821253
TI  - Obesity and breast cancer: status of leptin and adiponectin in pathological
      processes.
AB  - It is well recognized that obesity increases the risk of various cancers,
      including breast malignancies in postmenopausal women. Furthermore, obesity may
      adversely affect tumor progression, metastasis, and overall prognosis in both pre
      and postmenopausal women with breast cancer. However, the precise mechanism(s)
      through which obesity acts is/are still elusive and this relationship has been
      the subject of much investigation and speculation. Recently, adipose tissue and
      its associated cytokine-like proteins, adipokines, particularly leptin and
      adiponectin, have been investigated as mediators for the association of obesity
      with breast cancer. Higher circulating levels of leptin found in obese subjects
      could be a growth-enhancing factor as supported by in vitro and preclinical
      studies, whereas low adiponectin levels in obese women may be permissive for
      leptin's growth-promoting effects. These speculations are supported by in vitro
      studies which indicate that leptin promotes human breast cancer cell
      proliferation while adiponectin exhibits anti-proliferative actions. Further,
      estrogen and its receptors have a definite impact on the response of human breast
      cancer cell lines to leptin and adiponectin. More in-depth studies are needed to
      provide additional and precise links between the in vivo development of breast
      cancer and the balance of adiponectin and leptin.

PMID- 20821254
TI  - Association of fast-food restaurant and fruit and vegetable store densities with
      cardiovascular mortality in a metropolitan population.
AB  - Most studies that link neighbourhoods to disease outcomes have represented
      neighbourhoods as area-level socioeconomic status. Where objective contextual
      attributes of urban environments have been measured, few studies of food
      availability have evaluated mortality as an outcome. We sought to estimate
      associations between the availability of fast-food restaurants (FFR), fruit and
      vegetable stores (FVS), and cardiovascular mortality in an urban area. Food
      business data were extracted from a validated commercial database containing all
      businesses and services in the Montreal Census Metropolitan Area (MCMA).
      Mortality data (1999-2003) were obtained for the MCMA (3.4 million residents).
      Directly standardised mortality rates for cardiovascular deaths (n = 30,388) and
      non-cardiovascular deaths (all causes - cardiovascular deaths) (n = 91,132) and
      FFR and FVS densities (n/km2) were analysed for 845 census tracts. Generalised
      additive models and generalised linear models were used to analyse food source
      mortality relationships. FVS density was not associated with cardiovascular or
      non-cardiovascular mortality (relative risk (RR) = 1.02, 95% confidence interval
      (CI): 0.76, 1.36, and RR = 1.14, 95% CI: 0.87, 1.50, respectively). Higher FFR
      density was associated with mortality in bivariate and multivariable analyses.
      Relative risks of death (95% CI) per 10% increase in FFR density were similar for
      both cardiovascular and non-cardiovascular mortality: 1.39 (1.19, 1.63) and 1.36
      (1.18, 1.57), respectively, accounting for socio-demographic covariates. FFR
      density is associated with cardiovascular mortality but this relationship is no
      different in magnitude than that for non-cardiovascular mortality. These results
      together with null associations between FVS density and mortality do not support
      a major role for food source availability in cardiovascular outcomes.

PMID- 20821255
TI  - Cloning and characterization of the NPCEDRG gene promoter.
AB  - NPCEDRG is a novel tumor suppressive gene that localizes to 3p21.3, a chromosomal
      region frequently associated with loss of heterozygosity (LOH) in a number of
      malignancies including nasopharyngeal carcinoma (NPC). Its transcriptional down
      expression has been shown in the cell lines and primary tumor tissues of NPC.
      Reintroduction of NPCEDRG into CNE2, a cell line derived from NPC, was effective
      to induce cell differentiation, control cell growth, and regulate the cell cycle.
      Little is known about the transcriptional mechanisms controlling NPCEDRG gene
      expression. In this article, we describe the NPCEDRG gene structure and the
      transcriptional expression of NPCEDRG; we found that NPCEDRG was expressed weakly
      in most of NPC cell lines. Using 5' rapid amplification of complementary DNA ends
      (5'-RACEs), we found that the NPCEDRG gene has several transcription start sites
      (TSSs) due to the existence of alternatively spliced variants, and the specific
      TSS of NPCEDRG was located -25 nucleotides upstream of the translation start
      site. We amend that Human NPCEDRG CDS containing 516 bp but not the 510 bp
      reported previously. To characterize the NPCEDRG promoter, transient luciferase
      and/or EGFP reporter assay were carried out with the constructs including various
      lengths of the 5' flanking region of the NPCEDRG gene. The results demonstrated
      that the basal promoter is located at the region from -215 to -8 nucleotides, and
      the optimal promoter is located at the region from -625 to -8 nucleotides
      upstream of the translation start site. In silico analysis suggested that the
      promoter region contained potential binding sites for SP1, c-Myb, AREB6, Nkx2-5,
      and so on. These results provide important clues to elucidate the regulation of
      NPCEDRG gene expression and function. Further studies are apparently required for
      the identification of the transcription factors, essential for NPCEDRG
      expression, which would lead to better understanding of the molecular mechanism
      of NPCEDRG expression in nasopharyngeal epithelial cells.

PMID- 20821257
TI  - The longitudinal relationships between rural adolescents' prosocial behaviors and
      young adult substance use.
AB  - While many adolescents and young adults experiment with substances (e.g.,
      alcohol, cigarette smoking, marijuana), recent research suggests that rural youth
      and young adults may be more at risk for substance use than their urban
      counterparts. This study was designed to examine the longitudinal relationships
      between rural adolescents' prosocial behaviors and substance use in young
      adulthood. Furthermore, we examined the potential mediating effects of adolescent
      substance use, academic investment, and delinquency. Rural youth (N = 531; 263
      girls) were surveyed in grades 10-12 (Time 1; M age = 16.17; SD = .91) and again
      in early adulthood (Time 2). Measures of prosocial behaviors, substance use,
      academic investment, and deviant activities were assessed at Time 1. At Time 2,
      measures of marijuana use, cigarette smoking, and getting drunk were
      administered. Overall, the findings showed that rural adolescents who frequently
      exhibit prosocial behaviors are less likely to engage in substance use in young
      adulthood than those who exhibit relatively low levels of prosocial behaviors.
      These findings indicate that prosocial behaviors may have positive health
      consequences, establishing behavioral trajectories that lead to lower levels of
      risky health behaviors in adulthood in rural populations.

PMID- 20821256
TI  - Actin-sequestering protein, thymosin beta-4, is a novel hypoxia responsive
      regulator.
AB  - Angiogenesis is induced by soluble factors such as vascular endothelial growth
      factor (VEGF) released from tumor cells in hypoxia. It enhances solid tumor
      growth and provides an ability to establish metastasis at peripheral sites by
      tumor cell migration. Thymosin beta-4 (TB4) is an actin-sequestering protein to
      control cytoskeletal reorganization. Here, we investigated whether angiogenesis
      and tumor metastasis are dependent on hypoxia conditioning-induced TB4 expression
      in B16F10 melanoma cells. TB4 expression in B16F10 cells was increased by hypoxia
      conditioning in a time-dependent manner. In addition, we found an increase of
      angiogenesis and HIF-1alpha expression in TB4-transgenic (Tg) mice as compared to
      wildtype mice. When wound healing assay was used to assess in vitro tumor cell
      migration, hypoxia conditioning for 1 h enhanced B16F10 cell migration. When TB4
      expression in B16F10 cells was inhibited by the infection with small hairpin (sh)
      RNA of TB4 cloned in lentiviral vector, tumor cell migration was retarded. In
      addition, hypoxia conditioning-induced tumor cell migration was reduced by the
      infection of lentiviral shRNA of TB4. HIF-1alpha stabilization and the expression
      of VEGF isoform 165 and 121 in hypoxia were also reduced by the infection of
      lentiviral shRNA of TB4 in B16F10 cells. We also found an increase of tumor
      growth and lung metastasis count in TB4-Tg mice as compared to wildtype mice.
      Collectively, hypoxia conditioning induced tumor cell migration by TB4 expression
      dependent HIF-1alpha stabilization. It suggests that TB4 could be a hypoxia
      responsive regulator to control tumor cell migration in angiogenesis and tumor
      metastasis.

PMID- 20821259
TI  - Is experimental research passe.

PMID- 20821258
TI  - The application of the preschool Child Behavior Checklist and the caregiver
      teacher report form to Mainland Chinese children: syndrome structure, gender
      differences, country effects, and inter-informant agreement.
AB  - Preschool children have long been a neglected population in the study of
      psychopathology. The Achenbach System of Empirically Based Assessment (ASEBA),
      which includes the Child Behavior Checklist/1.5-5 (CBCL/1.5-5) and the Caregiver
      Teacher Report Form (C-TRF), constitutes the few available measures to assess
      preschoolers with an empirically derived taxonomy of preschool psychopathology.
      However, the utility of the measures and their taxonomy of preschool
      psychopathology to the Chinese is largely unknown and has not been studied. The
      present study aimed at testing the cross-cultural factorial validity of the
      CBCL/1.5-5 and C-TRF, as well as the applicability of the taxonomy of preschool
      psychopathology they embody, to Mainland Chinese preschoolers. Country effects
      between our Chinese sample and the original U.S. sample, gender differences, and
      cross-informant agreement between teachers and parents were also to be examined.
      A Chinese version of the CBCL/1.5-5 and C-TRF was completed by parents and
      teachers respectively on 876 preschoolers in Mainland China. Confirmatory factor
      analysis (CFA) confirmed the original, U.S.-derived second order, multi-factor
      model best fit the Chinese preschool data of the CBCL/1.5-5 and C-TRF. Rates of
      total behavior problems in Chinese preschoolers were largely similar to those in
      American preschoolers. Specifically, Chinese preschoolers scored higher on
      internalizing problems while American preschoolers scored higher on externalizing
      problems. Chinese preschool boys had significantly higher rates of externalizing
      problems than Chinese preschool girls. Cross-informant agreement between Chinese
      teachers and parents was relatively low compared to agreement in the original
      U.S. sample. Results support the generalizability of the taxonomic structure of
      preschool psychopathology derived in the U.S. to the Chinese, as well as the
      applicability of the Chinese version of the CBCL/1.5-5 and C-TRF.

PMID- 20821260
TI  - IGF-1 reduces BACE-1 expression in PC12 cells via activation of PI3-K/Akt and
      MAPK/ERK1/2 signaling pathways.
AB  - Insulin-like growth factor 1 (IGF-1) stimulates alpha-secretase processing of
      amyloid precursor protein (APP) and decreases Abeta production. Little is known
      about the relationship between IGF-1 and beta-site amyloid precursor protein
      cleaving enzyme 1 (BACE-1), the protease essential for the production of beta
      amyloid peptides (Abeta). Here, we investigated the effect of IGF-1 on BACE-1 in
      PC12 cells. Quantitative polymerase chain reaction analysis and western blot
      showed that treatment of cells with IGF-1 significantly decreased the levels of
      BACE-1 mRNA and protein. Furthermore, IGF-1 increased the phosphorylation of Akt
      and ERK1/2. The presence of the phosphatidylinositol 3-kinase (PI3-K) inhibitor
      LY294002 and the mitogen-activated protein kinase kinases (MEK) inhibitor PD98059
      blocked the effect of IGF-1 on BACE-1. Our data indicated that IGF-1-induced
      reduction of BACE-1 might involve the PI3-K/Akt and MAPK/ERK1/2 signaling
      pathways.

PMID- 20821261
TI  - Behavioral deficit and decreased GABA receptor functional regulation in the
      hippocampus of epileptic rats: effect of Bacopa monnieri.
AB  - In the present study, alterations of the General GABA and GABA(A) receptors in
      the hippocampus of pilocarpine-induced temporal lobe epileptic rats and the
      therapeutic application of Bacopa monnieri and its active component Bacoside-A
      were investigated. Bacopa monnieri (Linn.) is a herbaceous plant belonging to the
      family Scrophulariaceae. Hippocampus is the major region of the brain belonging
      to the limbic system and plays an important role in epileptogenesis, memory and
      learning. Scatchard analysis of [3H]GABA and [3H]bicuculline in the hippocampus
      of the epileptic rat showed significant decrease in B(max) (P < 0.001) compared
      to control. Real Time PCR amplification of GABA(A) receptor sub-units such as
      GABA(Aalpha1), GABA(Aalpha5) GABA(Adelta), and GAD were down regulated (P <
      0.001) in the hippocampus of the epileptic rats compared to control. GABA(Agamma)
      subunit was up regulated. Epileptic rats have deficit in the radial arm and Y
      maze performance. Bacopa monnieri and Bacoside-A treatment reverses all these
      changes near to control. Our results suggest that decreased GABA receptors in the
      hippocampus have an important role in epilepsy associated behavioral deficit,
      Bacopa monnieri and Bacoside-A have clinical significance in the management of
      epilepsy.

PMID- 20821262
TI  - Potential of shock waves to remove calculus and biofilm.
AB  - Effective calculus and biofilm removal is essential to treat periodontitis. Sonic
      and ultrasonic technologies are used in several scaler applications. This was the
      first feasibility study to assess the potential of a shock wave device to remove
      calculus and biofilms and to kill bacteria. Ten extracted teeth with visible
      subgingival calculus were treated with either shock waves for 1 min at an energy
      output of 0.4 mJ/mm(2) at 3 Hz or a magnetostrictive ultrasonic scaler at medium
      power setting for 1 min, which served as a control. Calculus was determined
      before and after treatment planimetrically using a custom-made software using a
      grey scale threshold. In a second experiment, multispecies biofilms were formed
      on saliva-preconditioned bovine enamel discs during 64.5 h. They were
      subsequently treated with shock waves or the ultrasonic scaler (N = 6/group)
      using identical settings. Biofilm detachment and bactericidal effects were then
      assessed. Limited efficiency of the shock wave therapy in terms of calculus
      removal was observed: only 5% of the calculus was removed as compared to 100%
      when ultrasound was used (P <= 0.0001). However, shock waves were able to
      significantly reduce adherent bacteria by three orders of magnitude (P <=
      0.0001). The extent of biofilm removal by the ultrasonic device was statistically
      similar. Only limited bactericidal effects were observed using both methods.
      Within the limitations of this preliminary study, the shock wave device was not
      able to reliably remove calculus but had the potential to remove biofilms by
      three log steps. To increase the efficacy, technical improvements are still
      required. This novel noninvasive intervention, however, merits further
      investigation.

PMID- 20821263
TI  - Parental violence and adolescent mental health.
AB  - Being the target of parental violent acts decreases child adjustment and
      increases the likelihood of mental health problems in childhood and adolescence.
      Our study analyses how different types of parental violence ranging from verbal
      threats and swearing to hitting and kicking a child, are associated with child
      adjustment, indicated by strengths and difficulties scale (SDQ) total problem
      score, internalizing and externalizing problems as well as prosocial behaviour.
      We also study whether girls and boys and youths in two Nordic countries respond
      differently to parental violence. The data consists of a large-scale community
      sample of 15-16-year old Finnish (n = 5,762) and Danish (n = 3,943) adolescents.
      The representative data of continental Finland and its Finnish and Swedish
      speaking ninth graders as well as representative data of Danish ninth grade
      pupils were collected by the Police College of Finland and in Denmark by the
      National Institute of Public Health, University of Southern Denmark. The results
      show a clear dose-response effect between parental violent behaviour and the
      adolescent's problems. The more severe forms of parental violence were associated
      with higher levels of SDQ total difficulties and internalizing and externalizing
      symptoms. There was also a connection between parental violence and the
      deterioration of prosocial behaviour. The association was gender and nationality
      specific. The findings imply a high prevalence of parental violence and adverse
      mental health among the affected Finnish and Danish adolescents. Though the laws
      have been set in motion to prevent the use of parental physical violence the
      challenges remain in several domains of child protection, general health care,
      prevention and intervention.

PMID- 20821264
TI  - Childhood predictors of later psychiatric hospital treatment: findings from the
      Finnish 1981 birth cohort study.
AB  - Psychiatric hospital treatment (PHT) is expensive and indicates a severe
      disorder. Investigation of the early identification of this small patient group
      has though been hindered by small samples or unsatisfactory assessment in
      childhood. The present study aims to study the predictive association between
      psychopathology at age 8 using multi-informant assessment and later PHT. A
      nationwide birth cohort of Finnish children (n = 5,346) was assessed at age 8 to
      obtain information about psychopathology using the Rutter parent and teacher
      reports and self-reports of depressive symptoms. The main outcome was admission
      to any hospital with a primary diagnosis of any psychiatric disorder according to
      the Finnish National Hospital Discharge Register between age 13 and 24. Between
      age 13 and 24, 6.2% of the males and 4.1% of the females had been admitted for
      PHT. Among males, PHT was independently predicted by non-intact family and adult
      reports of conduct and of emotional symptoms, while among females by self
      reported depressive symptoms. However, the combination of conduct and emotional
      problems was the strongest predictor for PHT in both sexes. Admission due to
      psychosis among males was associated with childhood conduct, attention, and
      emotional problems, but with emotional problems among females. Psychopathology at
      age 8 can be seen as a long-lasting increased risk of severe psychiatric
      disorders requiring hospital treatment in adolescence or early adulthood.
      Attention should be paid to self-reports among females and of comorbid conduct
      and emotional problems in both sexes in the early identification of this patient
      group.

PMID- 20821266
TI  - Assessing psychological symptoms in recent immigrant adolescents.
AB  - Immigrant youth are often exposed to numerous psychosocial stressors, placing
      them at risk for psychological distress. Little research assesses psychopathology
      in this population during early stages of acculturation. This study compared
      student and teacher reports of psychological symptoms in a diverse sample of
      recently immigrated youth. Students (N = 174) attended public high schools in a
      northeastern city. Students and teachers independently completed the Achenbach
      System of Empirically Based Assessment, and four DSM-derived subscales were
      explored. Psychological symptoms among immigrant students were higher than
      normative rates. Across all subscales, teacher ratings of student symptoms were
      significantly lower than student self-reported symptoms, and this difference was
      larger than that found in a normative sample. Results suggest that many immigrant
      youth experience psychological problems but may not be perceived as being in
      distress. Therefore, the most effective assessment approach may be active
      screening, rather than relying on self initiated help-seeking or teacher
      observation alone.

PMID- 20821265
TI  - The evolutionary consequences of oxygenic photosynthesis: a body size
      perspective.
AB  - The high concentration of molecular oxygen in Earth's atmosphere is arguably the
      most conspicuous and geologically important signature of life. Earth's early
      atmosphere lacked oxygen; accumulation began after the evolution of oxygenic
      photosynthesis in cyanobacteria around 3.0-2.5 billion years ago (Gya).
      Concentrations of oxygen have since varied, first reaching near-modern values
      ~600 million years ago (Mya). These fluctuations have been hypothesized to
      constrain many biological patterns, among them the evolution of body size. Here,
      we review the state of knowledge relating oxygen availability to body size.
      Laboratory studies increasingly illuminate the mechanisms by which organisms can
      adapt physiologically to the variation in oxygen availability, but the extent to
      which these findings can be extrapolated to evolutionary timescales remains
      poorly understood. Experiments confirm that animal size is limited by
      experimental hypoxia, but show that plant vegetative growth is enhanced due to
      reduced photorespiration at lower O(2):CO(2). Field studies of size distributions
      across extant higher taxa and individual species in the modern provide
      qualitative support for a correlation between animal and protist size and oxygen
      availability, but few allow prediction of maximum or mean size from oxygen
      concentrations in unstudied regions. There is qualitative support for a link
      between oxygen availability and body size from the fossil record of protists and
      animals, but there have been few quantitative analyses confirming or refuting
      this impression. As oxygen transport limits the thickness or volume-to-surface
      area ratio-rather than mass or volume-predictions of maximum possible size cannot
      be constructed simply from metabolic rate and oxygen availability. Thus, it
      remains difficult to confirm that the largest representatives of fossil or living
      taxa are limited by oxygen transport rather than other factors. Despite the
      challenges of integrating findings from experiments on model organisms,
      comparative observations across living species, and fossil specimens spanning
      millions to billions of years, numerous tractable avenues of research could
      greatly improve quantitative constraints on the role of oxygen in the
      macroevolutionary history of organismal size.

PMID- 20821267
TI  - The diagnosis of Cushing's syndrome.
AB  - Spontaneous Cushing's syndrome is well known but unusual clinical disorder. Many
      of the clinical features (central weight gain, glucose intolerance, hypertension,
      muscle weakness) are seen in other common conditions. Recognition of patients
      with multiple features, features unusual for their age (i.e. early onset
      osteoporosis or hypertension), patients with features more specific to Cushing's
      syndrome (i.e. easy bruising, facial plethora, and violaceous striae), and
      patients with incidental adrenal mass or polycystic ovary syndrome should prompt
      an evaluation for cortisol excess. Late-night salivary cortisol, 1 mg overnight
      dexamethasone suppression testing, or 24 h urine free cortisol determination have
      excellent diagnostic characteristics and should be obtain in patients with
      suspected Cushing' syndrome. If this initial testing is abnormal, further
      evaluation should be directed by an endocrinologist experienced in the diagnosis
      and differential diagnosis of Cushing' syndrome.

PMID- 20821268
TI  - Unmasking of undiagnosed pre-existing central diabetes insipidus after renal
      transplantation.
AB  - Acquired central diabetes insipidus (CDI) often occurs abruptly after a cranial
      event causing hypothalamic or pituitary damage. We present a case of a patient
      with pre-existing and clinically unapparent CDI which was unmasked after renal
      transplantation. A 60 year old woman with end-stage renal failure due to
      autosomal dominant polycystic kidney disease (ADPKD) underwent renal
      transplantation. She was noted to be markedly polyuric and polydipsic after the
      transplant. A fluid deprivation test was unequivocally positive for CDI, and
      desmopressin treatment resulted in immediate symptom relief. Neuroimaging
      revealed a midline defect in the region of the hypothalamus. She had a history of
      an intracerebral aneurysm that had ruptured, requiring extensive neurosurgery
      many years previously. This case demonstrates a rare instance of pre-existing but
      clinically unapparent CDI unmasked by renal transplantation. It is likely that
      renal failure due to ADPKD disguised her CDI prior to transplantation. A previous
      intracerebral insult from an aneurysmal bleed is the likely cause of her
      vasopressin deficiency.

PMID- 20821269
TI  - On the shoulders of giants: Harvey Cushing's experience with acromegaly and
      gigantism at the Johns Hopkins Hospital, 1896-1912.
AB  - A review of Dr. Cushing's surgical cases at Johns Hopkins Hospital revealed new
      information about his early operative experience with acromegaly. Although in
      1912 Cushing published selective case studies regarding this work, a review of
      all his operations for acromegaly during his early years has never been reported.
      We uncovered 37 patients who Cushing treated with surgical intervention directed
      at the pituitary gland. Of these, nine patients who presented with symptoms of
      acromegaly, and one with symptoms of gigantism were selected for further review.
      Two patients underwent transfrontal 'omega incision' approaches, and the
      remaining eight underwent transsphenoidal approaches. Of the 10 patients, 6 were
      male. The mean age was 38.0 years. The mean hospital stay was 39.4 days. There
      was one inpatient death during primary interventions (10%) and three patients
      were deceased at the time of last follow-up (33%). The mean time to death,
      calculated from the date of the primary surgical intervention, and including
      inpatient and outpatient deaths, was 11.3 months. The mean time to last follow
      up, calculated from the day of discharge, was 59.3 months. At the time of last
      follow-up, two patients reported resolution of headache; four patients reported
      continued visual deficits, and two patients reported ongoing changes in mental
      status. This review analyzes the outcomes for 10 patients who underwent surgical
      intervention for acromegaly or gigantism, and offers an explanation for Cushing's
      transition from the transfrontal "omega incision" to the transsphenoidal approach
      while practicing at the Johns Hopkins Hospital.

PMID- 20821270
TI  - The potential benefits of a garlic and hydrochlorothiazide combination as
      antihypertensive and cardioprotective in rats.
AB  - The purpose of the present study was to investigate the protective effects of
      combined therapy of garlic homogenate and hydrochlorothiazide (HCTZ) in animals
      with hypertension and myocardial damage. Three weeks of high fructose (10% w/v)
      in fluid to albino rats resulted in hypertension. They were subsequently
      administered garlic (125, 250 and 500 mg/kg, 3 weeks in separate groups) and HCTZ
      (10 mg/kg, 6th week) once daily in their respective groups. At the end of 6
      weeks, myocardial damage was induced by subcutaneous administration of
      isoproterenol (175 mg/kg) for 2 consecutive days. The results showed that garlic
      and HCTZ increase the lactate dehydrogenase, creatinine phosphokinase, superoxide
      dismutase and catalase activities in heart homogenate when used concurrently or
      separately. Further, restoration of normal values in fluid/food intake, body
      weight, systolic blood pressure, cholesterol, triglycerides, glucose and
      histopathological scores were observed in all treated groups. Furthermore,
      histological disturbances and hypertension were significantly ameliorated in
      treated animals. Moreover, moderate dose of garlic was more effective than low
      dose, while a high dose of garlic was least effective in correcting
      electrocardiographic changes. Thus it is concluded that garlic in moderate dose
      (250 mg/kg) with added HCTZ possesses synergistic cardioprotective and
      antihypertensive properties against fructose- and isoproterenol-induced
      toxicities.

PMID- 20821271
TI  - Phenolic glycosides from Rhodohypoxis baurii.
AB  - Three new phenolic glycosides (1-3), together with a known glycoside (4), were
      isolated from the bulbs of Rhodohypoxis baurii (Hypoxidaceae). The structures of
      the new glycosides (1-3) were determined on the basis of extensive spectroscopic
      analyses, including two-dimensional (2D) NMR data, and of hydrolytic cleavage
      followed by chromatographic or spectroscopic analyses.

PMID- 20821274
TI  - Abstracts of the Annual General Meeting of the Irish Cardiac Society. October 7
      9, 2010. Rosses Point, County Sligo, Ireland.

PMID- 20821275
TI  - Competing with oneself: introducing self-interaction in a model of competitive
      learning.
AB  - A competitive learning model was introduced in Mehta and Luck (Phys Rev E 60,
      5:5218-5230, 1999), in which the learning is outcome-related. Every individual
      chooses between a pair of existing strategies or types, guided by a combination
      of two factors: tendency to conform to the local majority, and a preference for
      the type with higher perceived success among its neighbors, based on their
      relative outcomes. Here, an extension of the interfacial model of Mehta and Luck
      (Phys Rev E 60, 5:5218-5230, 1999) is proposed, in which individuals additionally
      take into account their own outcomes in arriving at their outcome-based choices.
      Three possible update rules for handling bulk sites are considered. The
      corresponding phase diagrams, obtained at coexistence, show systematic departures
      from the original interfacial model. Possible relationships of these variants
      with the cooperative model of Mehta and Luck (Phys Rev E 60, 5:5218-5230, 1999)
      are also touched upon.

PMID- 20821276
TI  - Refractory congenital chylous ascites.
AB  - Refractory congenital chylous ascites (CCA) is an uncommon clinical condition.
      Few cases have been described and no gold standard treatment has been defined so
      far. This report describes a case of refractory CCA in a newborn child which was
      treated by surgery. Preoperative lower-limb lymphoscintigraphy associated with
      intraoperative patent blue testing and fibrin glue application were useful in
      order to provide a successful outcome.

PMID- 20821277
TI  - Management of raised intracranial pressure.
AB  - Appropriate management of raised intracranial pressure begins with stabilization
      of the patient and simultaneous assessment of the level of sensorium and the
      cause of raised intracranial pressure. Stabilization is initiated with securing
      the airway, ventilation and circulatory function. The identification of
      surgically remediable conditions is a priority. Emergent use of external
      ventricular drain or ventriculo-peritoneal shunt may be lifesaving in selected
      patients. In children with severe coma, signs of herniation or acutely elevated
      intracranial pressure, treatment should be started prior to imaging or invasive
      monitoring. Emergent use of hyperventilation and mannitol are life saving in such
      situations. Medical management involves careful use of head elevation, osmotic
      agents, and avoiding hypotonic fluids. Appropriate care also includes avoidance
      of aggravating factors. For refractory intracranial hypertension, barbiturate
      coma, hypothermia, or decompressive craniectomy should be considered.

PMID- 20821278
TI  - Utility of CT Scan in detection of melamine--associated urinary stones.
AB  - OBJECTIVE: To detail the utility of CT scan in detection of urinary stones
      induced by melamine tainted formula. MATERIAL AND METHODS: A total of 1062
      children fed with melamine-contaminated infant formula were screened for urinary
      stones in our institute from September through December 2008. Ultrasonography of
      the urinary tract system was performed in all these children. If the children
      with suspected stones or severe obstruction were presented after ultrasound
      examination, the multi-detector row CT urographic examination was advocated
      subsequently. RESULTS: Ultrasound examination in combination with multi-detector
      row CT urography could increase the diagnostic rate from 3.4% (36/1062) by
      ultrasound examination alone to 4.6% (49/1062). CONCLUSIONS: The specificity and
      sensitivity of the multi-detector row CT urographic examination is higher than
      ultrasonography.

PMID- 20821279
TI  - Waist circumference and mesenteric fat in neonates: negative correlation.
AB  - OBJECTIVE: To measure mesenteric fat thickness with ultrasound scan in neonates
      and to assess the correlation with waist circumference. METHODS: Ninety five
      healthy newborns had the maximum thickness of mesenteric leaves measured by
      ultrasound examinations of abdomen with an Envisor scanner (Philips Ultrasound,
      Bothell, Wash) and a L12-5 transducer (Philips Ultrasound). The correlation
      between the thickness of mesenteric leaves with abdominal waist was calculated.
      RESULTS: Maximum thickness of mesenteric leaves ranged from 0.24 to 1.00 mm (x =
      0.57 +/- 0.17) . There was a significant negative correlation between abdominal
      waist (AW) and mesenteric fat thickness (r = -0.384; p < 0.001). CONCLUSIONS:
      Mesenteric fat thickness in newborns is inversely associated with waist
      circumference. Higher visceral adiposity in neonates may be a protective
      mechanism from intrauterine growth restriction however this could persist into
      adulthood life.

PMID- 20821280
TI  - Hypoglycemia in the newborn.
AB  - Hypoglycemia in a neonate is defined as blood sugar value below 40 mg/dL. It is
      commonly associated with a variety of neonatal conditions like prematurity,
      intrauterine growth restriction and maternal diabetes. Screening for hypoglycemia
      in high-risk situations is recommended. Supervised breast-feeding may be an
      initial treatment option in asymptomatic hypoglycemia. However, symptomatic
      hypoglycemia should always be treated with a continuous infusion of parenteral
      dextrose. Neonates needing dextrose infusion rates above 12 mg/kg/min should be
      investigated for a definite cause of hypoglycemia. Hypoglycemia has been linked
      to poor neuro-developmental outcome, and hence aggressive screening and treatment
      is recommended.

PMID- 20821281
TI  - Vaccine related reactogenicity for primary immunization: a randomized controlled
      trial of 23(wider) vs. 25(narrower) gauge needles with same lengths.
AB  - OBJECTIVES: To compare vaccine related reactogenicity during primary immunization
      in healthy infants using 23 vs. 25 gauge needles. METHODS: This randomized
      controlled trial was conducted in Vaccination Room of the Advanced Pediatrics
      Center. 155 participants for primary immunization were assigned to two
      intervention groups (23 vs. 25 gauge). Parent-reported local and systemic
      reactions were recorded daily for three days after the immunization. RESULTS:
      Swelling (24%) and tenderness (21%) were the two most common parent-reported
      local symptoms followed by restriction of movements (18%) and redness (10%) on
      day 1. Any local reaction on day 1 was statistically similar in 25 gauge vs. 23
      gauge group (RR 0.77; 95% CI: 0.32 to 1.82) (P = 0.54), but fever (day 1) showed
      higher trend in 23 gauge needle group (RR 2.24; 95% CI: 0.92-5.47) (P = 0.07).
      Furthermore, on analysis of serially reported local and systemic reactions for 3
      consecutive days by generalized estimating equations, odds of redness, swelling,
      tenderness, restricted movement and fever were statistically similar between two
      needle groups. On the other hand, median (+/- SE) crying time (in seconds) was
      significantly prolonged in the 25 gauge needle (39 +/- 2) as compared to 23 gauge
      group (30 +/- 1.3) (log rank test, P = 0.001). CONCLUSIONS: The use of same
      length needles with narrower (25) or wider (23) gauge did not show significant
      differences in local reactogenicity during primary immunization. Fever, however,
      was reduced marginally in 25 gauge group whereas crying duration was
      significantly shorter with 23 gauge needle. Finally, larger studies are needed to
      further evaluate objectively the outcome of reactogenicity.

PMID- 20821282
TI  - Hyponatremia in birth asphyxia--cause or effect?

PMID- 20821283
TI  - Efficacy of communication DEALL--an indigenous early intervention program for
      children with autism spectrum disorders.
AB  - OBJECTIVE: To establish the efficacy of Communication DEALL, an indigenous early
      intervention program; in the management of children with autism spectrum
      disorders (ASD). METHODS: ABA design of pre intervention assessment, intervention
      and post intervention assessment was utilized, across an 8 month period. The
      first set of measures covered the assessment of developmental skills in the eight
      areas of gross motor skills, fine motor skills, activities of daily life skills,
      receptive language, and expressive language, cognitive, social and emotional
      skills. The second independent measure was the rating of each child on the
      Childhood Autism Rating Scale. Parental observations and parental estimation of
      the child's progress were also recorded. The study was conducted in the Com DEALL
      units in Bangalore, including thirty subjects diagnosed with ASD. Main Outcome
      Measures were developmental skill gains and decrease in behavioral issues.
      RESULTS: Statistically significant increase in all eight developmental domains
      and statistically significant decrease in behavioral symptoms as measured by the
      CARS, were seen. CONCLUSIONS: Thus, the Communication DEALL program shows promise
      as an effective early intervention program. It also indicates a need to further
      enhance the stabilization of the pre linguistic skills such as maintenance of eye
      contact, attention, sitting tolerance and compliance, in the program.

PMID- 20821284
TI  - Approach to a child with monoarthritis.
AB  - Arthritis in childhood is common. The pattern, presentation and duration of
      arthritis help differentiate between the various possible diagnoses. When only
      one joint is involved, i.e., monoarthritis, it may be difficult to make a
      diagnosis as there are many possibilities both acute and chronic in nature. A
      detailed history and clinical examination is important to reach a correct
      diagnosis and the single most important investigation when a child presents
      acutely is a joint aspiration to rule out septic arthritis that may destroy the
      joint in hours. Inflammatory markers, antinuclear antibody testing, test for
      tuberculosis and imaging (in specific cases) play an important role in the
      diagnosis of a child that presents with a chronic monoarthritis. In this article
      we provide a clinical approach to the diagnosis of monoarthritis in a child.

PMID- 20821285
TI  - Getting (the most) out of the research business: interventions for youth with
      T1DM.
AB  - We review research on psychosocial interventions to improve outcomes for youth
      with type 1 diabetes mellitus. Specifically, we discuss individual- and small
      group-focused, family-focused, group-focused, and other interventions. After
      reviewing extant research in each area, we discuss how the current evidence base
      may be used to inform clinical practice. Finally, we conclude by discussing
      variations in effects of interventions on different outcomes (eg, glycemic
      control, family functioning) and how to consider this evidence when selecting
      treatments to transport into clinical settings.

PMID- 20821286
TI  - Assessment of pharmacotherapy for negative symptoms of schizophrenia.
AB  - Negative symptoms in schizophrenia include diminished ability to communicate,
      motivate, and socialize as potentially debilitating aspects of the illness that
      are associated with long-term impairment. Despite such burden, the domain has
      been underrepresented in drug development and treatment research. In this
      article, we review research regarding pharmacotherapy for negative symptoms, with
      a focus on studies published during the past 2 years. Clearly positive studies
      were limited to N-methyl-D-aspartate agonists, while antipsychotics and
      antidepressants did not show substantial benefit, and cognitive enhancers have
      yielded mixed results. Proof-of-concept studies of other agents such as
      minocycline and omega fatty acids yielded promising, albeit preliminary findings
      that warrant replication. Study outcomes and designs are discussed along with
      implications for future research.

PMID- 20821287
TI  - Different mechanisms underlie post-menarchial increase in depression and weight.
AB  - BACKGROUND: Depression and being overweight are correlated health problems in
      adulthood. Adolescence is a significant period for the onset and increase of
      depression and obesity, especially among girls. Pubertal development also occurs
      with concomitant increases in weight. Thus, it is not yet clear whether the
      association between depression and being overweight can be explained by pubertal
      development. PURPOSE: We examined the association between depressive mood, body
      weight, and pubertal status in adolescent girls. METHOD: The design was cross
      sectional. In 962 young adolescent Dutch girls (age range, 11.9-15.9) weight and
      height measurements were used to calculate height, age, and gender-standardized
      body weight (zBMI). Questionnaires assessed depressive mood (the Center for
      Epidemiological Studies-Depression, CES-D, inventory) and menarcheal status (pre
      or post). RESULTS: The correlation between menarcheal status and body weight (r =
      0.34, p < 0.001) was not affected by depressive mood, and the correlation between
      menarcheal status and depressive mood (r = 0.20, p < 0.001) was not affected by
      body weight. A small correlation between depressive mood and body weight (r =
      0.12, p < 0.01) largely disappeared after controlling for menarche. CONCLUSION:
      Menarcheal status largely explains the association between weight and depression.
      It is independently associated with both BMI and depression, suggesting that
      different mechanisms underlie the post-menarcheal increased prevalence of
      depression and overweight.

PMID- 20821289
TI  - Four new species and a new Chinese record of the nectrioid fungi.
AB  - Four new species belonging to Bionectria, Calonectria, Haematonectria and
      Neonectria on plant substrates collected from nature reserves in southern and
      central China are described. Bionectria truncata has smooth perithecia of a
      flattened to shallow discoid apex, clavate asci with an apical ring, and
      ellipsoid, smooth to spinulose ascospores. Calonectria dicephalospora is
      characterized by pyriform perithecia with a warted surface, clavate asci with a
      simple apex and long, narrow stalk, and fusoid ascospores with a cap-like
      appendage at each end. Haematonectria lushanensis possesses warted perithecia
      which are laterally collapsing when dry, cylindrical asci with a simple apex, and
      ellipsoid, spinulose ascospores. Neonectria dinghushanica is distinguishable by
      subglobose perithecia with a warted surface, clavate asci, and striate
      ascospores. Morphological features of these new species are described
      comprehensively and compared with their related fungi. Neonectria castaneicola is
      recorded as new to China.

PMID- 20821288
TI  - Culture of human breast cancer cell line (MDA-MB-231) on fibronectin-coated
      surface induces pro-matrix metalloproteinase-9 expression and activity.
AB  - Interaction between cell surface integrin receptors with extracellular matrix
      (ECM) plays an important role in cell survival, proliferation, and migration
      including tumor development and invasion. Binding of ECM to integrins initiates
      intracellular signaling cascades, modulating expression and activity of different
      matrix metalloproteinases (MMPs) which is important in ECM degradation. The
      present study investigates fibronectin-integrin-mediated signaling and thereby
      modulation of MMPs expression and activity in human breast cancer cell line, MDA
      MB-231. Culture of MDA-MB-231 cells on fibronectin (FN) induced expression and
      activity of pro-matrixmetalloproteinase-9 (MMP-9). Appreciable reduction of FN
      induced pro-MMP-9 activity was observed in anti-alpha5 antibody treated cells.
      Inhibitor studies revealed that inhibitors of phosphatidyl inositiol-3-kinase (PI
      3K), and nuclear factor kappa B (NF-kappaB) inhibited FN-induced pro-MMP-9
      activity. FN increased tyrosine phosphorylation of focal adhesion kinase (FAK),
      integrin linked kinase (ILK), and PI-3K in MDA-MB-231 cells. FN-induced the
      transactivation of MMP-9 promoter by enhancing DNA binding activity of NF-kappaB
      and Sp1. Wound healing assay showed faster migration of MDA-MB-231cells grown on
      fibronectin-coated as surface as compared to control. Our findings indicated that
      culture of MDA-MB-231 on fibronectin perhaps send signals via fibronectin
      integrin-mediated signaling pathways recruiting FAK, PI-3K, ILK, NF-kappaB, and
      modulate expression and activation of pro-MMP-9. These observations may enrich
      fundamental aspects of cancer biology especially role of alpha5beta1 integrin in
      regulation of MMPs expression and activity.

PMID- 20821290
TI  - The tricks plants use to reach appropriate light.
AB  - The perception of ambient light signals that produce a relevant response to
      ensure exposure to appropriate levels of light energy is vital for plants. In
      response to this, intricate molecular mechanisms to mediate light signaling have
      evolved in plants. Among the responses induced by light, seedling extension is a
      determining event for plant survival in darkness, especially in the initial stage
      of plant growth. Here we review previous studies and recent progress towards an
      understanding of light signaling that regulates seedling elongation. We focus on
      the three regions of the sunlight spectrum that primarily control seedling
      elongation, namely red/far-red light, blue/UV-A light and UV-B light, and
      summarize the four signaling pathways that correspond to the three effective
      spectra.

PMID- 20821291
TI  - What we have learned from transcript profile analyses of male and female gametes
      in flowering plants.
AB  - Double fertilization is one of the predominant features of sexual reproduction in
      flowering plants but, because of the physical inaccessibility of gametes, the
      essential molecular mechanisms in these processes are largely unknown. Based on
      the techniques for isolating highly purified gametes from several species and
      well-developed methods for manipulating RNA from limited quantities of gametes,
      genome-wide investigations of gamete transcription profiles were recently
      conducted in flowering plants. In this review, we survey the accumulated
      knowledge on gamete collection and purification, cDNA library construction, and
      transcript profile analysis to assess our understanding of the molecular
      mechanisms of gamete specialization and fertilization.

PMID- 20821292
TI  - Cotton bollworm resistance to Bt transgenic cotton: a case analysis.
AB  - Cotton bollworm (Helicoverpa armigera) is one of the most serious insect pests of
      cotton. Transgenic cotton expressing Cry toxins derived from a soil bacterium,
      Bacillus thuringiensis (Bt), has been produced to target this pest. Bt cotton has
      been widely planted around the world, and this has resulted in efficient control
      of bollworm populations with reduced use of synthetic insecticides. However,
      evolution of resistance by this pest threatens the continued success of Bt
      cotton. To date, no field populations of bollworm have evolved significant levels
      of resistance; however, several laboratory-selected Cry-resistant strains of H.
      armigera have been obtained, which suggests that bollworm has the capacity to
      evolve resistance to Bt. The development of resistance to Bt is of great concern,
      and there is a vast body of research in this area aimed at ensuring the continued
      success of Bt cotton. Here, we review studies on the evolution of Bt resistance
      in H. armigera, focusing on the biochemical and molecular basis of Bt resistance.
      We also discuss resistance management strategies, and monitoring programs
      implemented in China, Australia, and India.

PMID- 20821293
TI  - The metabolic switch and its regulation in cancer cells.
AB  - The primary features of cancer are maintained via intrinsically modified
      metabolic activity, which is characterized by enhanced nutrient supply, energy
      production, and biosynthetic activity to synthesize a variety of macromolecular
      components during each passage through the cell cycle. This metabolic shift in
      transformed cells, as compared with non-proliferating cells, involves aberrant
      activation of aerobic glycolysis, de novo lipid biosynthesis and glutamine
      dependent anaplerosis to fuel robust cell growth and proliferation. Here, we
      discuss the unique metabolic characteristics of cancer, the constitutive
      regulation of metabolism through a variety of signal transduction pathways and/or
      enzymes involved in metabolic reprogramming in cancer cells, and their
      implications in cancer diagnosis and therapy.

PMID- 20821294
TI  - Progress in the development of therapeutic antibodies targeting prion proteins
      and beta-amyloid peptides.
AB  - Prion diseases and Alzheimer's disease (AD) are characterized by protein
      misfolding, and can lead to dementia. However, prion diseases are infectious and
      transmissible, while AD is not. The similarities and differences between these
      diseases have led researchers to perform comparative studies. In the last 2
      decades, progress has been made in immunotherapy using anti-prion protein and
      anti-beta-amyloid antibodies. In this study, we review new ideas and strategies
      for therapeutic antibodies targeting prion diseases and AD through conformation
      dependence.

PMID- 20821295
TI  - New insights into the species problem.
AB  - Historical opinions of the "species problem" are briefly reviewed, and four
      salient stages are recognized according to origin of species concepts. We propose
      that species is the unit preserving superior gene assembly and is maintained by
      specific mechanisms. Based on characteristics of plant evolution, we assume that
      understanding plant species may include three stages, i.e. morphological
      recognition stage, multidisciplinary verification stage, and illuminating
      mechanisms preserving superior gene assembly.

PMID- 20821296
TI  - Quantitative assessment of toxic and nontoxic Microcystis colonies in natural
      environments using fluorescence in situ hybridization and flow cytometry.
AB  - Toxic cyanobacterial blooms constitute a threat to human safety because
      Microcystis sp. releases microcystins during growth, and particularly during cell
      death. Therefore, analysis of toxic and nontoxic Microcystis in natural
      communities is required in order to assess and predict bloom dynamics and toxin
      production by these organisms. In this study, an analysis combining fluorescence
      in situ hybridization (FISH) with flow cytometry (FCM) was used to discriminate
      between toxic and nontoxic Microcystis and also to quantify the percentage of
      toxic Microcystis present in blooms. The results demonstrate that the combination
      of FISH and flow cytometry is a useful approach for studying the ecology of
      Microcystis toxin production and for providing an early warning for toxic
      Microcystis blooms.

PMID- 20821297
TI  - A decade of Bt cotton in Chinese fields: assessing the direct effects and
      indirect externalities of Bt cotton adoption in China.
AB  - The objective of this study is to examine whether or not the gains from reduced
      spraying for bollworms are being sustained more than one decade after the initial
      adoption in 2007. Based on farm-level data collected by the authors in 1999-2007
      in 16 villages from 4 provinces, this study shows that insecticides applied for
      controlling bollworms have declined. This analysis supports Chinese policy
      makers' decision to not require refuges of non-Bt cotton fields. It also suggests
      that past studies may have underestimated the benefits from adopting Bt
      technology.

PMID- 20821298
TI  - DNA barcoding provides distinction between Radix Astragali and its adulterants.
AB  - Based on variable nuclear and/or organellar DNA sequences among vastly divergent
      species as well as morphologically indistinguishable species, DNA barcoding is
      widely applicable in species identification, biodiversity studies, forensic
      analyses, and authentication of medicinal plants. The roots of Astragalus
      membranaceus and A. membranaceus var. mongholica are commonly used as Radix
      Astragali in several Asian countries, including China, Japan, and Korea. However,
      in addition to the two species recorded in the Chinese Pharmacopoeia, there are
      twenty-three species from different genera including Astragalus, Oxytropis,
      Hedysarum, and Glycyrrhiza, which have been used as adulterants not only in
      trading markets but also by the herbal medicine industry. Therefore, a simple,
      reliable, and accurate classification method is important for distinguishing
      authentic Radix Astragali from its adulterants. In this study, we acquired data
      for 37 samples from four related genera within the family Fabaceae. Then we
      compared four candidate DNA barcoding markers using ITS, matK, rbcL, and coxI
      sequences from nuclear, chloroplast, and mitochondrial genomes, all commonly used
      for plants to identify genetic variations among genera, intraspecies, and
      interspecies. We observed higher divergences among genera and interspecies for
      ITS, which have the average Kimura 2-parameter distances of 4.5% and 14.1%,
      respectively, whereas matK was found to have sufficient divergence at the
      intraspecific level. Moreover, two indels detected in the matK sequence are
      useful for PCR studies in distinguishing Radix Astragali from its adulterants.
      This study suggests that the combined barcoding regions of ITS and matK are
      superior barcodes for Radix Astragali and further studies should focus on
      evaluating the applicability and accuracy of such combined markers for a wide
      range of traditional Chinese herbs.

PMID- 20821299
TI  - Fibroblast growth factor (FGF)-21 signals through both FGF receptor-1 and 2.
AB  - Fibroblast growth factor (FGF)-21 is a member of the FGF superfamily based on
      sequence homology. However, unlike most members of this family it does not show
      any mitogenic activity in all cell types tested. The objective of this study is
      to identify and characterize receptors for this molecule. Sequencing of the cDNA
      clones from 3T3-L1 adipocytes indicates that the only isoforms for FGFR-1 and 2
      expressed in 3T3-L1 cells are 1IIIc and 2IIIc, respectively, suggesting that FGF
      21 regulates glucose metabolism in 3T3-L1 adipocytes through FGFR-1IIIc and FGFR
      2IIIc.

PMID- 20821300
TI  - Taxol inhibits stretch-induced electrophysiological alterations in isolated rat
      hearts with acute myocardial infarction.
AB  - Mechanosensitive channels have been determined to work as transducers of
      mechanoelectric feedback in the heart, which is associated with the generation of
      arrhythmias. Recent studies have investigated the role of the cytoskeleton in ion
      channels control. This study explored the ability of taxol to inhibit stretch
      induced electrophysiological alterations in the ischemic myocardium. Thirty-two
      Wistar rats were randomly divided into four groups: normal control group (n=9),
      taxol group (n=7), myocardial infarction (MI) group (n=9), and MI+taxol group
      (n=7). After Langendorff perfusion, the isolated hearts were stretched for 5 s by
      balloon inflation to 0.2 or 0.3 mL. The effects of stretching on 90% monophasic
      action potential duration (MAPD(90)), premature ventricular beats (PVB), and
      ventricular tachycardia (VT) were observed for 30 s. Stretching increased
      MAPD(90) in both the normal control and MI groups, but MAPD(90) increased more in
      the MI group for the same degree of stretch. Taxol (5 mumol L(-1)) had no effect
      on MAPD(90) under baseline, unstretched conditions, but MAPD(90) in the taxol
      group was slightly increased after stretching compared with the normal control
      group (P>0.05). However, taxol reduced MAPD(90) in infarcted myocardium (P<0.05
      at DeltaV=0.3 mL). The incidences of PVB and VT in the MI group were higher than
      in the normal control group (both P<0.01). Taxol had no effect on the occurrence
      of arrhythmias in normal myocardium, but it inhibited PVB and VT in infarcted
      hearts (both P<0.01). Thus changes in MAPD and the occurrence of arrhythmias
      caused by mechanical stretching of the myocardium could be inhibited by taxol in
      isolated rat hearts during AMI, indicating the involvement of tubulin in
      mechanoelectric feedback in AMI.

PMID- 20821301
TI  - Expression and function of heregulin-alpha and its receptors in the mouse mammary
      gland.
AB  - Heregulin-alpha (HRGalpha) is a cytokine secreted by the mammary mesenchyme,
      adjacent to lobuloalveolar structures. To understand the role of HRGalpha and its
      receptors in mammary glands, and the underlying mechanisms, we performed this
      study to determine the expression and localization of HRGalpha and its receptors
      ErbB2 and ErbB3. We also determined the role of HRGalpha in the development of
      mammary glands, beta-casein expression and secretion, Rab3A protein expression
      and the phosphorylation of HRGalpha signaling molecules using confocal laser
      scanning microscopy, tissue culture, capillary electrophoresis, Western blotting
      and enzyme-linked immunosorbent assays. We found that a peak was on pregnancy day
      15. Changes of ErbB2 and ErbB3 expression were positively and linearly correlated
      with HRGalpha, indicating that HRGalpha positively regulates ErbB2 and ErbB3
      expression. During pregnancy, HRGalpha enhanced the phosphorylation of STAT5,
      p42/p44, p38, PKC and Rab3A protein expression, stimulated the proliferation and
      differentiation of the ductal epithelial cells of mammary glands, and increased
      and maintained the expression and secretion of beta-casein. During lactation,
      HRGalpha enhanced the phosphorylation of STAT5 and p38, inhibited the
      phosphorylation of PKC and Rab3A protein expression, maintained the morphology of
      the mammary glands and increased the secretion of lactoprotein to reduce the
      expression of beta-casein in mammary epithelial cells. During involution,
      HRGalpha induced the phosphorylation of STAT3 and Rab3A protein expression, and
      inhibited the phosphorylation of PKC to stimulate the degeneration of mammary
      epithelial cells. It also inhibited the secretion of beta-casein, resulting in
      increased levels of beta-casein in mammary epithelial cells.

PMID- 20821302
TI  - DNA barcoding, phylogenetic relationships and speciation of snappers (genus
      Lutjanus).
AB  - The phylogenetic relationships of 13 snapper species from the South China Sea
      have been established using the combined DNA sequences of three full-length
      mitochondrial genes (COI, COII and CYTB) and two partial nuclear genes (RAG1,
      RAG2). The 13 species (genus Lutjanus) were selected after DNA barcoding 72
      individuals, representing 20 species. Our study suggests that although DNA
      barcoding aims to develop species identification systems, it may also be useful
      in the construction of phylogenies by aiding the selection of taxa. Combined
      mitochondrial and nuclear gene data has an advantage over an individual dataset
      because of its higher resolving power.

PMID- 20821303
TI  - Spatiotemporal expression of Pax genes in amphioxus: insights into Pax-related
      organogenesis and evolution.
AB  - The expression of four AmphiPax genes in 16 developmental stages and different
      organs in amphioxus (Branchiostoma belcheri) was investigated, finding those
      genes expressed throughout amphioxus life with temporal-specific (especially
      during embryogenesis and metamorphosis) and spatial-specific patterns. This study
      suggests that duplicated Pax genes in vertebrates might maintain most of their
      ancestral functions and also expand their expression patterns after the
      divergence of protochordates and vertebrates.

PMID- 20821304
TI  - Asymmetric interaction will facilitate the evolution of cooperation.
AB  - Explaining the evolution of cooperation remains one of the greatest problems for
      both biology and social science. The classical theories of cooperation suggest
      that cooperation equilibrium or evolutionary stable strategy between partners can
      be maintained through genetic similarity or reciprocity relatedness. These
      classical theories are based on an assumption that partners interact
      symmetrically with equal payoffs in a game of cooperation interaction. However,
      the payoff between partners is usually not equal and therefore they often
      interact asymmetrically in real cooperative systems. With the Hawk-Dove model, we
      find that the probability of cooperation between cooperative partners will depend
      closely on the payoff ratio. The higher the payoff ratio between recipients and
      cooperative actors, the greater will be the probability of cooperation
      interaction between involved partners. The greatest probability of conflict
      between cooperative partners will occur when the payoff between partners is
      equal. The results show that this asymmetric relationship is one of the key
      dynamics of the evolution of cooperation, and that pure cooperation strategy
      (i.e., Nash equilibrium) does not exist in asymmetrical cooperation systems,
      which well explains the direct conflict observed in almost all of the well
      documented cooperation systems. The model developed here shows that the cost-to
      benefit ratio of cooperation is also negatively correlated with the probability
      of cooperation interaction. A smaller cost-to-benefit ratio of cooperation might
      be created by the limited dispersal ability or exit cost of the partners
      involved, and it will make the punishment of the non-cooperative individuals by
      the recipient more credible, and therefore make it more possible to maintain
      stable cooperation interaction.

PMID- 20821305
TI  - Sequencing and analysis of the giant panda genome.

PMID- 20821307
TI  - Metabolically engineered male sterility in rapeseed (Brassica napus L.).
AB  - Male sterility is of special interest as a mechanism allowing hybrid breeding,
      especially in important crops such as rapeseed (Brassica napus). Male sterile
      plants are also suggested to be used as a biological safety method to prevent the
      spread of transgenes, a risk that is high in the case of rapeseed due to the mode
      of pollination, out-crossing by wind or insects, and the presence of related,
      cross-pollinating species in the surrounding ecosystem in Europe. Different
      natural occurring male sterilities and alloplasmic forms have been tried to be
      used in rapeseed with more or less success. Due to the difficulties and
      limitations with these systems, we present a biotechnological alternative: a
      metabolically engineered male sterility caused by interference with anther
      specific cell wall-bound invertase. This is an essential enzyme for carbohydrate
      supply of the symplastically isolated pollen. The activity of this enzyme is
      reduced either by antisense interference or by expressing an invertase inhibitor
      under control of the anther-specific promoter of the invertase with the
      consequence of a strong decrease of pollen germination ability.

PMID- 20821308
TI  - Outcome of transvaginal pelvic reconstructive surgery with Prolift after a median
      of 2 years' follow-up.
AB  - INTRODUCTION AND HYPOTHESIS: This study seeks to analyze the medium- to long-term
      outcome of transvaginal pelvic reconstructive surgery using the ProliftTM system
      for pelvic organ prolapse. METHODS: Sixty-five patients who underwent pelvic
      floor reconstruction using ProliftTM were followed for 1 to 3 years
      postoperatively. Assessment included pre- and postoperative Pelvic Organ Prolapse
      Quantification (POP-Q) stage, Urogenital Distress Inventory (UDI-6), and
      Incontinence Impact Questionnaire (IIQ-7) scores. RESULTS: The overall anatomic
      success rate was 97% after a median of 24.5 months and 94% for the 34 women
      followed for more than 2 years. POP-Q stage, UDI-6, and IIQ-7 scores all improved
      significantly after surgery. Complications included one bladder perforation
      (1.5%) and one bowel perforation (1.5%), prolonged catheterization in four
      patients (6%), and mesh erosion in one (2%). Eight received blood transfusion
      (12%). CONCLUSIONS: ProliftTM surgery yielded a good anatomical outcome and
      satisfactory symptom improvement that appeared to be durable after 2 years.

PMID- 20821309
TI  - Intrasphincteric injections of autologous muscular cells in women with refractory
      stress urinary incontinence: a prospective study.
AB  - INTRODUCTION AND HYPOTHESIS: Cell therapy for stress urinary incontinence (SUI)
      management has been experienced with encouraging results. METHODS: We conducted
      an open prospective study on 12 women presenting severe SUI with fixed urethra,
      after previous failed surgical management. Patients underwent intrasphincteric
      injections of autologous progenitor muscular cells isolated from a biopsy of
      deltoid muscle. Primary endpoint focused on safety (measurement of Q(max)
      variation after 3 months). Secondary endpoints assessed side effects and
      efficacy. RESULTS: No variation was diagnosed on Q(max) measurements. Efficacy
      data show that three of 12 patients are dry at 12 months, seven other patients
      are improved on pad test but not on voiding diary, and two patients were slightly
      worsened by the procedure. Quality of life was improved in half of patients.
      CONCLUSIONS: Cell therapy for severe multioperated cases of SUI is a mini
      invasive, feasible, and safe procedure that can improve urinary condition in as a
      second line therapy.

PMID- 20821310
TI  - Ringing the changes in evaluation of urogenital prolapse.
AB  - INTRODUCTION AND HYPOTHESIS: Some women with pelvic organ prolapse (POP) have
      occult urodynamic stress incontinence (OUSI) and might develop incontinence after
      POP surgery. Our aim was to determine predictive value of ring pessary test
      during urodynamics in identifying patients with OUSI, likely to develop stress
      urinary incontinence (SUI) postoperatively. METHODS: Women with POP were
      recruited from surgical lists. All underwent preoperative videocystourethrography
      (VCU). Women with normal VCUs had tests repeated after pessary reduction of POP.
      RESULTS: One hundred and twelve women were studied. Forty-eight women had
      "normal" VCU. Of these, 43 had no OUSI and only 1/43 developed SUI
      postoperatively. Five women had OUSI and 2/5 developed frank SUI. The pessary
      test had poor sensitivity (67%) but high specificity (93%) in predicting
      postoperative SUI. Positive predictive value was low (40%), with an excellent
      negative predictive value (98%). CONCLUSION: This test can identify patients
      likely to remain continent following surgery and be a valuable tool in
      preoperative counselling.

PMID- 20821311
TI  - Correlation between shrinkage and infection of implanted synthetic meshes using
      an animal model of mesh infection.
AB  - INTRODUCTION AND HYPOTHESIS: the aim of this study was to evaluate a link between
      mesh infection and shrinkage. METHODS: twenty-eight Wistar rats were implanted
      with synthetic meshes that were either non-absorbable (polypropylene (PP), n =
      14) or absorbable (poly (D: ,L: -lactic acid) (PLA94), n = 14). A validated
      animal incisionnal abdominal hernia model of mesh infection was used. Fourteen
      meshes (n = 7 PLA94 and n = 7 PP meshes) were infected intraoperatively with 10e6
      CFU Escherichia coli, and compared with 14 non-infected meshes (n = 7 PLA94 and n
      = 7 PP meshes) (control groups). Explantations were performed on day 30.
      Shrinkage was evaluated by a reproducible numerical analysis of mesh area.
      Infection and histological study were evaluated on day 30. RESULTS: non-infected
      meshes were less shrunk than infected meshes for both non-absorbable (5.0 +/-
      1.7% versus 21.6 +/- 6.1%, p < 0.05) and absorbable meshes (2.4 +/- 0.9% versus
      11.0 +/- 2.5%, p < 0.05). CONCLUSION: this study highlights a link between
      infection and shrinkage in the model used.

PMID- 20821312
TI  - Dramatic increase (1997-2007) in the number of procedures for stress urinary
      incontinence in Belgium.
AB  - INTRODUCTION AND HYPOTHESIS: We wondered if the tension-free vaginal tape
      approach, introduced in 1998, influenced the rate of anti-incontinence surgery.
      METHODS: We determined the rates of anti-incontinence surgery in Belgium between
      1997 and 2007, using the Belgian National Health Insurance Fund register covering
      the entire adult female population of nearly 4,420,000 women in Belgium. RESULTS:
      The rate per 1,000 women of anti-incontinence surgery increased from 0.54 in 1997
      to 2.03 in 2004, after which a plateau was reached (2.01 in 2007). This nearly
      fourfold increase coincided with the introduction in 1998 on the Belgian market
      of the tension-free vaginal tape (+66% more interventions between 1998 and 2001).
      After the introduction of the transobturator tape in 2001, the rate increased
      even more dramatically (+118% between 2001 and 2004). CONCLUSIONS: Rates of anti
      incontinence surgery increased by 272% in Belgium between 1997 and 2007. This
      increase coincided with the availability of tension-free mesh sling operations.

PMID- 20821313
TI  - Tandem mass spectrometry identification and LC-MS quantification of intact
      cytokinin nucleotides in K-562 human leukemia cells.
AB  - We describe here a new reversed-phase high-performance liquid chromatography with
      mass spectrometry detection method for quantifying intact cytokinin nucleotides
      in human K-562 leukemia cells. Tandem mass spectrometry was used to identify the
      intracellular metabolites (cytokinin monophosphorylated, diphosphorylated, and
      triphosphorylated nucleotides) in riboside-treated cells. For the protein
      precipitation and sample preparation, a trichloroacetic acid extraction method is
      used. Samples are then back-extracted with diethyl ether, lyophilized,
      reconstituted, and injected into the LC system. Analytes were quantified in
      negative selected ion monitoring mode using a single quadrupole mass
      spectrometer. The method was validated in terms of retention time stabilities,
      limits of detection, linearity, recovery, and analytical accuracy. The developed
      method was linear in the range of 1-1,000 pmol for all studied compounds. The
      limits of detection for the analytes vary from 0.2 to 0.6 pmol.

PMID- 20821314
TI  - Waffle-cone technique with SolitaireTM AB remodeling device: endovascular
      treatment of highly selected complex cerebral aneurysms.
AB  - INTRODUCTION: To evaluate patients with complex aneurysms who underwent waffle
      cone stent-assisted coil embolization. METHODS: From February 2008 to February
      2010, consecutive data were collected from 80 patients with aneurysms treated
      with the SolitaireTM AB Remodeling Device followed by a standard coiling
      procedure using bare or/and bioactive coils. Six of these patients were treated
      using the "waffle-cone-technique" placing the distal end of a stent directly into
      the base of a bifurcation aneurysm and coiling through the expanded and cone
      shaped distal end of the stent allowing for preservation of parent artery
      patency. The aneurysms were located at the P3 segment of the posterior cerebral
      artery (n = 1), the middle cerebral artery bifurcation (n = 1), the basilar tip
      (n = 2), and the AComAnt (n = 2). Four patients underwent follow-up (2-7 months,
      mean 4.5 months). RESULTS: Waffle-cone positioning of the SolitaireTM AB
      Remodeling Device was obtained in all cases without technical problems. No
      permanent procedural morbidity was observed. In all patients, a Raymond class 2
      occlusion was obtained and five patients left the hospital with a good clinical
      status (mRS0 n = 3, mRS1 n = 1) or no new neurologic deficits (mRS4 n = 1). One
      patient with SAH III died due to severe vasospasms. Due to major recanalization
      during follow-up, retreatment was necessary or is planned in four cases; one
      asymptomatic intimal hyperplasia was observed 8 weeks after initial treatment.
      CONCLUSION: The waffle-cone technique may enhance the possibilities of the
      endovascular treatment of these complex aneurysms. Due to the high rate of
      recanalization requiring endovascular retreatment, stringent angiographic and
      clinical follow-up is warranted.

PMID- 20821315
TI  - MHC class I and MHC class II DRB gene variability in wild and captive Bengal
      tigers (Panthera tigris tigris).
AB  - Bengal tigers are highly endangered and knowledge on adaptive genetic variation
      can be essential for efficient conservation and management. Here we present the
      first assessment of allelic variation in major histocompatibility complex (MHC)
      class I and MHC class II DRB genes for wild and captive tigers from India. We
      amplified, cloned, and sequenced alpha-1 and alpha-2 domain of MHC class I and
      beta-1 domain of MHC class II DRB genes in 16 tiger specimens of different
      geographic origin. We detected high variability in peptide-binding sites,
      presumably resulting from positive selection. Tigers exhibit a low number of MHC
      DRB alleles, similar to other endangered big cats. Our initial assessment
      admittedly with limited geographic coverage and sample size-did not reveal
      significant differences between captive and wild tigers with regard to MHC
      variability. In addition, we successfully amplified MHC DRB alleles from scat
      samples. Our characterization of tiger MHC alleles forms a basis for further in
      depth analyses of MHC variability in this illustrative threatened mammal.

PMID- 20821325
TI  - Leukemias induced by altered TRK-signaling are sensitive to mTOR inhibitors in
      preclinical models.
AB  - Rapamycin is a potent allosteric mTORC1 inhibitor with clinical applications as
      an anticancer agent. However, only a fraction of cancer patients responds to the
      drug, and no biomarkers are available to predict tumor sensitivity. Recently, we
      and others have obtained evidence for potential involvement of tropomyosin
      related kinase (TRK) receptor protein tyrosine kinases (TRKA, TRKB, TRKC) in
      leukemia. In the present study, we tested the therapeutic effect of Rapamycin and
      its analog RAD001 on altered TRK-induced leukemia in a murine model. Daily
      treatment with Rapamycin (2 mg/kg) or RAD001 (1 mg/kg) significantly prolonged
      the survival of treated animals (n = 40) compared with the placebo group.
      Consistently, both mTOR and S6 proteins were strongly dephosphorylated in vitro
      and in vivo after treatment with Rapamycin or RAD001. However, Rapamycin did not
      completely inhibit mTORC1-dependent phosphorylation of 4E-BP1. With exception of
      one mouse showing slight reactivation of Akt after treatment, no reactivation of
      MAPK or Akt pathways was observed in other resistant tumors. Interestingly,
      leukemic cells isolated from a Rapamycin-resistant mouse were still highly
      sensitive to Rapamycin in vitro. Our findings suggest that altered TRK signaling
      may be a good predictor of tumor sensitivity to mTOR inhibition and that pathways
      other than MAPK and Akt exist that may trigger resistance of leukemic cells to
      Rapamycin in vivo.

PMID- 20821326
TI  - Efficacy of the combination of bortezomib and dexamethasone in systemic AL
      amyloidosis.
AB  - Bortezomib-dexamethasone (Btz/Dex) is an active regimen in patients with multiple
      myeloma and has been used in few patients with amyloidosis. Here, we report a
      retrospective evaluation of the efficacy and toxicity of Btz/Dex in 26 patients
      with AL amyloidosis (AL). Eighteen patients (69%) received Btz/Dex as first-line
      treatment. Organs most frequently involved were kidneys (100%) and heart (35%);
      five patients (19%) had less than two organs involved. The overall response rate
      was 54% (14 of 26 patients), with eight patients (31%) achieving a hematologic
      complete remission (CR). All patients who reached a CR received Btz/Dex as first
      line therapy. Median time to response was 7.5 weeks. Improvement in organ
      function was noticed in three patients (12%). Median progression-free survival
      (PFS) and overall survival (OS) was 5.0 and 18.7 months, respectively; in CR
      patients, however, median PFS and OS have not yet been reached. Toxicities were
      manageable, with hematological side effects being most common. No grade 3/4
      neuropathy was observed. Our results confirm the activity of
      bortezomib/dexamethasone in patients with AL amyloidosis and suggest that
      patients achieving a CR have a marked benefit for survival.

PMID- 20821327
TI  - High prevalence of hepatitis B and hepatitis C virus infections in Korean
      patients with hematopoietic malignancies.
AB  - We performed a large case-control study (3,932 cases, 15,562 controls) to
      investigate the association of hepatitis B virus (HBV) and hepatitis C virus
      (HCV) with hematopoietic malignancies in Korea, where HBV is endemic. HBV was
      present in 636 control patients (4.1%), 333 lymphoma patients (12.4%), and 75
      leukemia patients (6.0%). HCV infection was present in 173 control patients
      (1.1%), 76 lymphoma patients (2.8%), and 18 leukemia patients (1.4%). Co
      infection of HBV and HCV was present in one (0.007%) control patient, seven
      lymphoma patients (0.3%), and one leukemia patient (0.08%). HBV infection was
      associated with increased risks for most subtypes of B and T/NK-cell lymphomas,
      Hodgkin's lymphoma, and acute myeloid leukemia. HCV infection was associated with
      increased risks for diffuse large B cell lymphoma, extranodal marginal zone B
      cell lymphoma, peripheral T cell lymphoma, and acute lymphoid leukemia B cell
      early pre-B type. HBV seems to have a more important role than HCV in the
      pathogenesis of specific hematologic malignancies in Korea.

PMID- 20821328
TI  - In vitro and in vivo antitumor effects of (4-methoxyphenyl)(3,4,5
      trimethoxyphenyl)methanone.
AB  - PURPOSE: (4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone (PHT) is a phenstatin
      analog compound. PHT is a known tubulin inhibitor that has potent cytotoxic
      activity. In the present study, PHT was synthesized and its antitumor activity
      was determined using in vitro and in vivo experimental models. METHODS: The in
      vitro cytotoxic activity of the PHT was determined by the MTT assay. The
      antimitotic and hemolytic effects were determined based on the inhibition of sea
      urchin embryo development and lysis of mouse erythrocytes, respectively. In vivo
      antitumor activity was assessed in mice inoculated with sarcoma 180 cells.
      RESULTS: In vitro, PHT displayed cytotoxicity in tumor cell lines, showing IC(50)
      values in the nanomolar range. In addition, it inhibited sea urchin embryo
      development during all phases examined, first and third cleavage and blastula
      stage. However, PHT did not induce hemolysis using mouse erythrocytes, suggesting
      that the cytotoxicity of PHT does not involve membrane damage. The in vivo study
      demonstrated tumor inhibition rates of 30.9 and 48.2% for PHT at doses of 20 and
      40 mg/kg, respectively. In addition, PHT was also able to increase the response
      elicited by 5-fluorouracil (5-FU) from 33.3 to 55.7%. The histopathological
      analysis of liver, kidney, and spleen showed that they were just moderately
      affected by PHT treatment. Neither enzymatic activity of transaminases nor urea
      levels were significantly affected. Hematological analysis showed leukopenia
      after 5-FU treatment, but this effect was prevented when 5-FU was combined with
      PHT. CONCLUSIONS: In conclusion, PHT exhibited in vitro and in vivo antitumor
      effects without substantial toxicity.

PMID- 20821329
TI  - Can localised (19)F magnetic resonance spectroscopy pharmacokinetics of 5FU in
      colorectal metastases predict clinical response?
AB  - BACKGROUND: 5-Fluorouracil remains widely used in colorectal cancer treatment
      more than 40 years after its development. 19F magnetic resonance spectroscopy can
      be used in vivo to measure 5FU's half-life and metabolism to cytotoxic
      fluoronucleotides. Previous studies have shown better survival associated with
      longer 5FU tumour half-life. This work investigated 5FU pharmacokinetics in liver
      metastases of colorectal cancer. METHODS: A total of 32 subjects with colorectal
      cancer undergoing 5FU treatment, 15 of whom had liver metastases, were examined
      in a 1.5T MRI scanner, using a large coil positioned over the liver. Non
      localised spectra were acquired in 1-min blocks for 32 min after injection of a
      5FU bolus. The 5FU half-life was measured in each subject, and averaged spectra
      were examined for the presence of fluoronucleotides. Associations with
      progression-free survival were assessed. RESULTS: No association was observed
      between 5FU half-life, tumour burden and survival. Half-lives were all shorter
      than those associated with improved survival in the literature. Remarkably, in
      the group with liver metastases, high levels of fluoronucleotides were associated
      with poorer survival; this counterintuitive result may be due to the higher
      levels of fluoronucleotides (whose level is higher in tumour tissue than in
      normal liver) in patients with higher tumour burdens. CONCLUSIONS: It is
      recommended that future studies use chemical shift imaging at higher field
      strengths to better resolve tumour from normal liver. Non-localised spectroscopy
      retains prognostic potential by enabling straightforward detection of
      fluoronucleotides, which are present at very low concentrations distributed
      throughout the tissue.

PMID- 20821330
TI  - Pegylated liposomal doxorubicin, 5-fluorouracil and cisplatin versus mitomycin-C,
      5-fluorouracil and cisplatin for advanced gastric cancer: a randomized phase II
      trial.
AB  - PURPOSE: Clinical data suggested that a regimen incorporating doxorubicin to 5
      fluorouracil (5-FU) and cisplatin may be more effective but probably quite toxic
      for advanced gastric cancer patients. With the aim to maintain efficacy while
      reducing toxicity, we compared the activity and safety of a combination of 5-FU,
      cisplatin and pegylated liposomal doxorubicin with a combination of 5-FU,
      cisplatin and mitomycin-C. PATIENTS AND METHODS: Seventy-eight patients were
      randomised to receive 5-FU (400 mg/m(2) bolus, 600 mg/m(2) 22 h continuous
      infusion day 1 and 2) and cisplatin (50 mg/m(2) day 1) every 2 weeks, combined
      either with pegylated liposomal doxorubicin (20 mg/m(2) day 1 every two weeks)
      (arm A) or mitomycin-C (7 mg/m(2) every 6 weeks) (arm B). RESULTS: The overall
      response rate was 64.1% in arm A and 38.5% in arm B (P = 0.041). The median time
      to tumour progression and overall survival were 7.93 and 5.14 months (P = 0.04)
      and 12.1 and 8.3 months (P = 0.02) in arm A and B, respectively. Fourteen
      patients in arm A and 18 patients in arm B experienced a grade 3/4 toxic effect.
      CONCLUSIONS: A combination of pegylated liposomal doxorubicin, cisplatin and 5-FU
      can be safely administered in gastric cancer patients with a promising efficacy
      profile.

PMID- 20821331
TI  - Pharmacokinetic results of a phase I trial of sorafenib in combination with
      dacarbazine in patients with advanced solid tumors.
AB  - PURPOSE: Sorafenib, a multikinase inhibitor of Raf and several growth factor
      receptors, is under investigation in combination with dacarbazine, a commonly
      used chemotherapeutic agent for the treatment of many cancers. The current phase
      I study investigates the effects of sorafenib on the pharmacokinetic (PK) profile
      of dacarbazine and its metabolite 5-amino-imidazole-4-carboxamide (AIC). (AIC is
      formed in amounts equimolar to the active alkylating moiety, methane
      diazohydroxide, which is undetectable by known validated assays.) METHODS:
      Patients with advanced solid tumors received intravenous dacarbazine 1,000
      mg/m(2) on day 1 of a 21-day cycle to evaluate the PK of dacarbazine alone.
      Sorafenib 400 mg was administered twice daily continuously starting at day 2 of
      cycle 1. The PK of dacarbazine in the presence of sorafenib was assessed on day 1
      of cycle 2. Sorafenib PK was also assessed at steady state. RESULTS: PK data were
      available for 15 of 23 patients. With concomitant administration of sorafenib,
      the mean AUC and C (max) values of dacarbazine were reduced by 23 and 16%,
      respectively. Mean AUC and C (max) values of AIC were increased by 41 and 45%,
      respectively, with individual increases of up to 106 and 136%, respectively. The
      apparent terminal half-lives of the two compounds were not significantly
      influenced by sorafenib. Based on coefficients of variation, the AUC and C (max)
      values for sorafenib and its three metabolites were highly variable with
      dacarbazine coadministration. CONCLUSIONS: Concomitant administration of
      sorafenib and dacarbazine as described above may result in decreased dacarbazine
      exposure but increased AIC exposure.

PMID- 20821332
TI  - [Comparison of superselective intraarterial fibrinolysis with conservative
      therapy. Use in patients with acute non-arteritic central retinal artery
      occlusion].
AB  - The results of conservative treatment for central retinal artery occlusion (CRAO)
      vary considerably and although local intraarterial fibrinolysis (LIF) is a
      promising treatment, outcomes have not been compared in randomized trials. The
      prospective randomized multicenter study by the European Assessment Group for
      Lysis in the Eye (EAGLE) is the first clinical trial to compare treatment
      outcomes of conservative standard treatment (CST) and LIF for acute non-arteritic
      CRAO. Patients (age 18-75 years) with CRAO present for less than 20 h and best
      corrected visual acuity (BCVA) <0.5 logMAR were randomized to either CST or LIF
      group. Primary endpoint was BCVA after 1 month and secondary endpoint was safety.
      Mean BCVA (logMAR) improved significantly in both groups and did not differ
      between the groups. Because of similar efficacy and the higher rate of adverse
      events in the LIF group the study was halted after the first interim analysis.
      Due to the similar outcomes of the two therapies and the higher rate of adverse
      reactions associated with LIF superselective lysis cannot be recommended for the
      management of acute CRAO.

PMID- 20821333
TI  - [PrefCheck: patient-centered treatment planning with older multimorbid patients.
      Method and design].
AB  - BACKGROUND: The aim of the study is to develop and test a consultation guide
      (PrefCheck) for general practitioners (GPs) based on geriatric assessment
      results. The goal of the consultation guide is to facilitate priority setting and
      treatment planning based on building a partnership with geriatric patients with
      multiple chronic diseases. METHODS AND AIMS: The mixed method study consists of
      three complementary parts: (A) health and treatment priorities of 32 patients and
      their 8 GPs are determined and explored on the basis of assessment results. These
      findings lead to the development of the consultation guide, which is subsequently
      tested in a cluster-randomized controlled intervention study (B) with 40 GPs and
      320 patients. The aim of this study is to assess whether PrefCheck results in
      improved agreement in the number of health and treatment priorities between
      patients and their doctors. The study concludes with an evaluation study (C) with
      5 GPs and 15 patients. CONCLUSIONS: Results will be presented in a future
      publication. In particular it will be demonstrated whether the consultation guide
      can strengthen the position of older patients in the doctor-patient relationship,
      increase the level of information on both sides, and contribute to a shared and
      holistic treatment planning.

PMID- 20821334
TI  - [Quality improvement in Germany: a way to better electrophysiology?].

PMID- 20821335
TI  - Voice handicap index and voice-related quality of life in small laryngeal
      carcinoma.
AB  - Laryngeal cancer can affect the patients' voice. For assessment of the patients'
      self-perception of their voice, several tools were introduced into clinical
      routine. The voice handicap index questionnaire (VHI) is regarded as the "gold
      standard". However, in benign laryngeal pathologies and in functional dysphonia,
      the shorter voice-related quality of life questionnaire (V-RQOL) proved to be
      equivalent. This study examines the correlation of both questionnaires in
      patients who had been treated for small (T1 and T2) laryngeal cancer. It was
      performed during regular outclinic examinations. In total, 65 patients aged 62.1
      +/- 10.0 years completed the German versions of the VHI and V-RQOL. Their average
      VHI total score was 38.9 +/- 26.0 points and the average V-RQOL score was 70.1 +/
      24.4%. The total scores correlated with |rho| = 0.92 and p < 0.01. Both
      questionnaires give quasi identical results, the shorter V-RQOL may be favoured
      for clinical application.

PMID- 20821336
TI  - Slow VO2 kinetics during moderate-intensity exercise as markers of lower
      metabolic stability and lower exercise tolerance.
AB  - An analysis of previously published data obtained by our group on patients
      characterized by markedly slower pulmonary VO2 kinetics (heart transplant
      recipients, patients with mitochondrial myopathies, patients with McArdle
      disease) was carried out in order to suggest that slow VO2 kinetics should not be
      considered the direct cause, but rather a marker, of impaired exercise tolerance.
      For a given ATP turnover rate, faster (or slower) VO2 kinetics are associated
      with smaller (or greater) muscle [PCr] decreases. The latter, however, should not
      be taken per se responsible for the higher (or lower) exercise tolerance, but
      should be considered within the general concept of "metabolic stability". Good
      muscle metabolic stability at a given ATP turnover rate (~power output) is
      associated with relatively smaller decreases, compared to rest, in [PCr] and in
      the Gibbs free energy of ATP hydrolysis, as well as with relatively smaller
      increases in [Pi], [ADP(free)], [AMP(free)], and [IMP(free)], metabolites
      directly related to fatigue. Disturbances in muscle metabolic stability can
      affect muscle function in various ways, whereas good metabolic stability is
      associated with less fatigue and higher exercise tolerance. Smaller [PCr]
      decreases, however, are strictly associated with a faster VO2 kinetics. Thus,
      faster VO2 kinetics may simply be an "epiphenomenon" of a relatively higher
      metabolic stability, which would then represent the relevant variable in terms of
      fatigue and exercise tolerance.

PMID- 20821337
TI  - Using public control genotype data to increase power and decrease cost of case
      control genetic association studies.
AB  - Genome-wide association (GWA) studies are a powerful approach for identifying
      novel genetic risk factors associated with human disease. A GWA study typically
      requires the inclusion of thousands of samples to have sufficient statistical
      power to detect single nucleotide polymorphisms that are associated with only
      modest increases in risk of disease given the heavy burden of a multiple test
      correction that is necessary to maintain valid statistical tests. Low statistical
      power and the high financial cost of performing a GWA study remains prohibitive
      for many scientific investigators anxious to perform such a study using their own
      samples. A number of remedies have been suggested to increase statistical power
      and decrease cost, including the utilization of free publicly available genotype
      data and multi-stage genotyping designs. Herein, we compare the statistical power
      and relative costs of alternative association study designs that use cases and
      screened controls to study designs that are based only on, or additionally
      include, free public control genotype data. We describe a novel replication-based
      two-stage study design, which uses free public control genotype data in the first
      stage and follow-up genotype data on case-matched controls in the second stage
      that preserves many of the advantages inherent when using only an
      epidemiologically matched set of controls. Specifically, we show that our
      proposed two-stage design can substantially increase statistical power and
      decrease cost of performing a GWA study while controlling the type-I error rate
      that can be inflated when using public controls due to differences in ancestry
      and batch genotype effects.

PMID- 20821338
TI  - Time processing in children and adults with ADHD.
AB  - A time-processing deficit has been proposed as a neuropsychological candidate
      endophenotype for Attention Deficit Hyperactivity Disorder (ADHD), but its
      developmental trajectory still needs to be explored. In the present study,
      children (N = 33) and adults (N = 22) with ADHD were compared to normal controls
      on two time-processing tasks. For time reproduction, ADHD-related impairment was
      found in the full group, but not when adults were analyzed separately. For the
      discrimination of brief intervals, children and adults with ADHD showed different
      patterns of deficit. We conclude that in ADHD some time-processing deficits are
      still present in adults, but may take on age-related different forms.

PMID- 20821339
TI  - In vivo evidence for functional NMDA receptor blockade by memantine in rat
      hippocampal neurons.
AB  - Antagonising the NMDA (N-methyl-D: -aspartate) receptor complex is a widely
      hypothesised therapeutic approach in several neurodegenerative conditions, such
      as Alzheimer's disease. Memantine, a moderate affinity uncompetitive NMDA
      receptor antagonist, has been in clinical use for several years and numerous
      experimental data support its NMDA receptor blocking effects. It has recently
      been reported in transfected HEK293T cells that physiological concentrations of
      Mg(2+) may impart partial NMDA receptor subtype selectivity and weaken the
      overall inhibitory actions of memantine in NMDA receptor-mediated cellular
      events. In the present study, we set out to investigate the effect of
      intravenously applied memantine on iontophoresed NMDA-evoked firing of
      hippocampal CA1 neurons using in vivo conditions. Cumulative doses of memantine
      in the rat (4, 8 and 16 mg/kg i.v.) caused the firing rate to decrease in a dose
      dependent manner to 77 +/- 7, 58 +/- 8 and 34 +/- 12% of control, respectively,
      while saline application had no significant effect. We show that therapeutic
      doses of memantine are able to antagonize NMDA receptor-mediated activity in the
      principal cells of the hippocampus in vivo, i.e. in the presence of physiological
      concentrations of Mg(2+).

PMID- 20821340
TI  - Diode laser treatment of Barrett's esophagus: long-term results.
AB  - Different ablation techniques have been utilized in the treatment of Barrett's
      esophagus (BE) to reduce the risk of degeneration. Treatment complications, risk
      of recurrence, and buried intestinal metaplasia (IM) are all major concerns. The
      effect of diode laser treatment on BE, studied in a group of patients over a long
      term period, is presented here. All patients with histology of IM or low-grade
      dysplasia (LGD) treated with diode laser therapy for BE and followed for at least
      24 months were included in the study. Treatment sessions were carried out every 3
      months and bioptic follow-up examinations were done yearly. Patients without
      antireflux surgery received proton pump inhibitors. A total of 20 patients with
      IM, four of them with LGD, were treated with 161 laser sessions (in mean eight
      per patient) without complications. Complete, sustained endoscopic and histologic
      remission was obtained in 13 patients (11/12 with BE <= 3 cm and 2/8 with BE >3
      cm, p < 0.01) and a mean of 83 +/- 27% of the metaplasic tissue was removed in
      all the patients. All four cases of LGD healed to squamous tissue. No buried
      metaplasia, recurrences, or disease progressions were reported after a mean
      follow-up of 6 years and 2 months. Diode laser ablation is a safe and effective
      method in most cases of short BE, while it is less effective in the long form,
      requiring a large number of sessions. Long-term results show that the risk of
      recurrence and of buried intestinal metaplasia underneath neosquamous epithelium
      is negligible.

PMID- 20821341
TI  - Muscle contraction: A mechanical perspective.
AB  - In this paper we present a purely mechanical analog of the conventional chemo
      mechanical modeling of muscle contraction. We abandon the description of kinetics
      of the power stroke in terms of jump processes and instead resolve the continuous
      stochastic evolution on an appropriate energy landscape. In general physical
      terms, we replace hard spin chemical variables by soft spin variables
      representing mechanical snap-springs. This allows us to treat the case of small
      and even disappearing barriers and, more importantly, to incorporate the
      mechanical representation of the power stroke into the theory of Brownian
      ratchets. The model provides the simplest non-chemical description for the main
      stages of the biochemical Lymn-Taylor cycle and may be used as a basis for the
      artificial micro-mechanical reproduction of the muscle contraction mechanism.

PMID- 20821342
TI  - Phase I trial with biomarker studies of vatalanib (PTK787) in patients with newly
      diagnosed glioblastoma treated with enzyme inducing anti-epileptic drugs and
      standard radiation and temozolomide.
AB  - Targeting angiogenesis in glioblastoma (GBM) may improve patient outcome by
      normalizing tumor vasculature and improving delivery of chemotherapeutics and
      oxygen. Consequently, concomitant administration of small molecule inhibitors of
      the VEGF pathway will likely have a positive impact on chemoradiation treatment
      outcome. We conducted a Phase I study of vatalanib, a small molecule inhibitor of
      VEGFR, PDGFR, and c-kit in patients with newly diagnosed GBM receiving radiation,
      temozolomide, and an enzyme-inducing anti-epileptic drug in order to determine
      the MTD of vatalanib in this patient population. We incorporated circulating
      biomarker and SNP analyses and pharmacokinetic studies. Nineteen patients were
      enrolled and the MTD was not reached at the time of study termination. Vatalanib
      was well tolerated with only 2 DLTs (thrombocytopenia and elevated
      transaminases). Other grade 3/4 toxicities included leukopenia, lymphopenia,
      neutropenia, and hand-foot syndrome. There were no wound-healing complications.
      Of the 13 patients evaluable for a radiographic response, 2 had a partial
      response and 9 had stable disease. Vatalanib significantly increased PlGF and
      sVEGFR1 in plasma circulation and decreased sVEGFR2 and sTie2. Plasma collagen IV
      increased significantly by day 50 of treatment. Vatalanib was well tolerated and
      this study demonstrates the safety of oral small molecule inhibitors in newly
      diagnosed GBM patients. Blood biomarkers may be useful as pharmacodynamic markers
      of response to anti-angiogenic therapies.

PMID- 20821343
TI  - Epidemiology and etiology of meningioma.
AB  - Although most meningiomas are encapsulated and benign tumors with limited numbers
      of genetic aberrations, their intracranial location often leads to serious and
      potentially lethal consequences. They are the most frequently diagnosed primary
      brain tumor accounting for 33.8% of all primary brain and central nervous system
      tumors reported in the United States between 2002 and 2006. Inherited
      susceptibility to meningioma is suggested both by family history and candidate
      gene studies in DNA repair genes. People with certain mutations in the
      neurofibromatosis gene (NF2) have a very substantial increased risk for
      meningioma. High dose ionizing radiation exposure is an established risk factor
      for meningioma, and lower doses may also increase risk, but which types and doses
      are controversial or understudied. Because women are twice as likely as men to
      develop meningiomas and these tumors harbor hormone receptors, an etiologic role
      for hormones (both endogenous and exogenous) has been hypothesized. The extent to
      which immunologic factors influence meningioma etiology has been largely
      unexplored. Growing emphasis on brain tumor research coupled with the advent of
      new genetic and molecular epidemiologic tools in genetic and molecular
      epidemiology promise hope for advancing knowledge about the causes of intra
      cranial meningioma. In this review, we highlight current knowledge about
      meningioma epidemiology and etiology and suggest future research directions.

PMID- 20821344
TI  - Podoplanin and CD34 in peripheral nerve sheath tumours: focus on
      neurofibromatosis 1-associated atypical neurofibroma.
AB  - Patients suffering from neurofibromatosis type 1 and 2 (NF1 and NF2) are the main
      risk groups to develop peripheral nerve sheath tumours (PNSTs). In the present
      study, adhesion molecules CD34 and podoplanin were assessed in regard to their
      value for tumour classification and as indicators for tumour progression. A total
      of 103 NF1-, NF2- and schwannomatosis-associated neurofibromas, schwannomas and
      malignant peripheral nerve sheath tumours (MPNST), as well as 20 sporadic
      vestibular schwannomas and 9 control tissue samples, were labelled
      immunohistochemically for detection of podoplanin and CD34. CD34 was shown to be
      expressed in MPNST and all benign PNSTs except for the compact cellular parts of
      both, schwannomas and atypical neurofibromas. Podoplanin showed an inverse
      expression pattern to CD34 labelling mainly the compact parts of schwannoma and
      atypical neurofibroma. MPNSTs were characterized by strong podoplanin staining at
      the invasive front. NF1-patients who suffered from atypical neurofibromas did not
      develop MPNST at a higher frequency than other NF1-patients, although these
      tumours expressed podoplanin. Ki-67 proliferation indices did not differ
      significantly between neurofibromas, atypical neurofibromas and schwannomas. In
      accordance with other studies, CD34 was found to be of limited value for
      classification and grading of PNST due to its ubiquitous expression. Podoplanin
      expression in schwannoma and atypical neurofibroma adds to other phenotypic and
      genotypic similarities between these tumours, like nuclear atypia, regressive
      changes and euploid polyploidisation. Podoplanin expression in atypical
      neurofibroma was not associated with tumour progression towards MPNST.

PMID- 20821345
TI  - Developing transgenic Anopheles mosquitoes for the sterile insect technique.
AB  - In the last 10 years the availability of the genome sequence of Anopheles gambiae
      and the development of a transgenic technology for several species of Anopheles
      mosquitoes have, in combination, helped in enabling us to gain several insights
      into the biology of these mosquitoes that is relevant to their capacity as
      vectors of the malaria parasite. While this information is anticipated to inform
      many novel vector control strategies, the technique most likely to benefit in the
      near future from the availability of a reliable transgenic technology is the
      sterile insect technique (SIT), which relies on releasing large numbers of
      sterile insects to compete for mates in the wild, leading to population
      suppression. Although SIT has been proven to work reliably for many insects, the
      construction of suitable strains, and induction of sterility, has until now been
      a laborious process, combining classical genetics with radiation-induced
      sterility. Using transgenesis to create strains of Anopheles suitable for SIT
      could potentially offer several advantages over current approaches, in that the
      basic design of transgenic constructs designed for other insects should be
      rapidly transferable to mosquitoes, and induction of sterility as a product of
      the transgenic modification could obviate the requirement for radiation and its
      associated deleterious effects. In this paper the progress of different
      transgenic approaches in constructing tools for SIT will be reviewed.

PMID- 20821346
TI  - Responses of Mikania micrantha, an invasive weed to elevated CO2: induction of
      beta-caryophyllene synthase, changes in emission capability and allelopathic
      potential of beta-caryophyllene.
AB  - To better understand the effect of predicted elevated levels of carbon dioxide
      (CO2) on an invasive weed Mikania micrantha, we constructed a suppressive
      subtractive hybridization (SSH) library from the leaves of M. micrantha exposed
      to CO2 at 350 and 750 ppm for 6 d, and isolated a novel gene named beta
      caryophyllene synthase. beta-Caryophyllene synthase catalyses the conversion of
      farnesyl diphosphate to beta-caryophyllene, a volatile sesquiterpene with
      allelopathic potential. Real-time PCR analysis revealed that gene expression of
      beta-caryophyllene synthase in M. micrantha leaves was strongly induced in
      response to elevated CO2. Gas chromatography-mass spectrometry (GC-MS) and gas
      chromatography (GC) analyses showed that emission levels of beta-caryophyllene
      from leaves of M. micrantha increased when exposed to 750 ppm CO2. Bioassays
      showed that phytotoxicity of beta-caryophyllene against Raphanus sativus,
      Brassica campestris, Lactuca sativa, and M. micrantha was dose-dependent and
      varied with the receptor plants and concentrations of CO2. beta-Caryophyllene
      displayed higher phytotoxic effects at 750 ppm than those at 350 ppm CO2,
      especially on R. sativus. These results suggest that elevated atmospheric CO2
      levels may enhance biosynthesis and phytotoxicity of allelochemicals in M.
      micrantha, one of the worst invasive weeds in the world, which in turn might
      enhance its potential allelopathic effect on neighboring native plants if
      released in bioactive concentrations. Further investigations are required to
      determine the adaptive responses of both invasive and native plants to a gradual
      increase of atmospheric CO2 to 750 ppm predicted over a 100 year period.

PMID- 20821347
TI  - Image-guided tumor resection using real-time near-infrared fluorescence in a
      syngeneic rat model of primary breast cancer.
AB  - Tumor involvement of resection margins is found in a large proportion of patients
      who undergo breast-conserving surgery. Near-infrared (NIR) fluorescence imaging
      is an experimental technique to visualize cancer cells during surgery. To
      determine the accuracy of real-time NIR fluorescence imaging in obtaining tumor
      free resection margins, a protease-activatable NIR fluorescence probe and an
      intraoperative camera system were used in the EMR86 orthotopic syngeneic breast
      cancer rat model. Influence of concentration, timing and number of tumor cells
      were tested in the MCR86 rat breast cancer cell line. These variables were
      significantly associated with NIR fluorescence probe activation. Dosing and tumor
      size were also significantly associated with fluorescence intensity in the EMR86
      rat model, whereas time of imaging was not. Real-time NIR fluorescence guidance
      of tumor resection resulted in a complete resection of 17 out of 17 tumors with
      minimal excision of normal healthy tissue (mean minimum and a mean maximum tumor
      free margin of 0.2 +/- 0.2 mm and 1.3 +/- 0.6 mm, respectively). Moreover, the
      technique enabled identification of remnant tumor tissue in the surgical cavity.
      Histological analysis revealed that the NIR fluorescence signal was highest at
      the invasive tumor border and in the stromal compartment of the tumor. In
      conclusion, NIR fluorescence detection of breast tumor margins was successful in
      a rat model. This study suggests that clinical introduction of intraoperative NIR
      fluorescence imaging has the potential to increase the number of complete tumor
      resections in breast cancer patients undergoing breast-conserving surgery.

PMID- 20821348
TI  - The rexinoid bexarotene represses cyclin D1 transcription by inducing the DEC2
      transcriptional repressor.
AB  - Bexarotene is an RXR-selective vitamin A analog that has been shown to prevent ER
      negative mammary tumorigenesis in animal models. While investigating the
      mechanism by which bexarotene prevents ER-negative breast cancer development, we
      found that the expression of cyclin D1, a critical cell cycle promoter, was
      repressed by bexarotene in vitro and in vivo. Time course and cycloheximide
      experiments show that repression of cyclin D1 is a late effect and requires new
      protein synthesis. Previously we discovered that DEC2 (differentially expressed
      in chondrocytes-2), a helix-loop-helix transcription repressor, was induced by
      bexarotene in human mammary epithelial cells. Therefore, we hypothesized that
      bexarotene represses the transcription of cyclin D1 through induction of DEC2.
      Luciferase reporter studies demonstrated that either bexarotene treatment or
      forced expression of DEC2 can repress the transcription of a cyclin D1 promoter
      reporter by affecting the basal transcriptional activity. Results from chromatin
      immunoprecipitation experiments showed that bexarotene treatment causes the
      recruitment of DEC2 and HDAC1 (histone deacetylase 1) to the cyclin D1 promoter.
      Co-immunoprecipitation confirms the interaction between DEC2 and HDAC1,
      suggesting that the recruitment of HDAC1 to the cyclin D1 promoter is through
      DEC2. Trichostatin A, a HDAC inhibitor, reverses the cyclin D1 repression by
      bexarotene, suggesting that repression of cyclin D1 involves histone
      deacetylation. Knock-down of DEC2 by siRNA abolishes the cyclin D1 repression,
      further supporting our hypothesis. Finally, we demonstrated that overexpression
      of DEC2 dramatically inhibited cell proliferation and repressed the expression of
      cyclin D1 in human mammary epithelial cells. These results suggest that
      bexarotene down-regulates cyclin D1 through induction of DEC2, followed by
      recruitment of HDAC1 to the cyclin D1 promoter causing transcriptional
      repression. By elucidating the mechanism by which rexinoids inhibit cell
      proliferation, it will be possible to develop more effective and less toxic drugs
      to prevent ER-negative breast cancers.

PMID- 20821349
TI  - Optimal delineation of ambulatory holter ECG events via false-alarm bounded
      segmentation of a wavelet-based principal components analyzed decision statistic.
AB  - The aim of this study is to develop and describe a new ambulatory holter
      electrocardiogram (ECG) events detection-delineation algorithm with the major
      focus on the bounded false-alarm probability (FAP) segmentation of an information
      optimized decision statistic. After implementation of appropriate preprocessing
      methods to the discrete wavelet transform (DWT) of the original ECG data, a
      uniform length sliding window is applied to the obtained signal and in each slid,
      six feature vectors namely as summation of the nonlinearly amplified Hilbert
      transform, summation of absolute first order differentiation, summation of
      absolute second order differentiation, curve length, area and variance of the
      excerpted segment are calculated to construct a newly proposed principal
      components analyzed geometric index (PCAGI) by application of a linear
      orthonormal projection. In the next step, the alpha-level Neyman-Pearson
      classifier (which is a FAP controlled tester) is implemented to detect and
      delineate QRS complexes. The presented method was applied to MIT-BIH Arrhythmia
      Database, QT Database, and T-Wave Alternans Database and as a result, the average
      values of sensitivity and positive predictivity Se = 99.96% and P+ = 99.96% are
      obtained for the detection of QRS complexes, with the average maximum delineation
      error of 5.7, 3.8 and 6.1 m for P-wave, QRS complex and T-wave, respectively.
      Also, the proposed method was applied to DAY general hospital high resolution
      holter data (more than 1,500,000 beats including Bundle Branch Blocks-BBB,
      Premature Ventricular Complex-PVC and Premature Atrial Complex-PAC) and average
      values of Se = 99.98% and P+ = 99.97% are obtained for QRS detection. In summary,
      marginal performance improvement of ECG events detection-delineation process in a
      widespread values of signal to noise ratio (SNR), reliable robustness against
      strong noise, artifacts and probable severe arrhythmia(s) of high resolution
      holter data and the processing speed 155,000 samples/s can be mentioned as
      important merits and capabilities of the proposed algorithm.

PMID- 20821350
TI  - Editorial: apoptosis in the aging brain.

PMID- 20821352
TI  - Generation of liver disease-specific induced pluripotent stem cells along with
      efficient differentiation to functional hepatocyte-like cells.
AB  - The availability of disease-specific induced pluripotent stem cells (iPSCs)
      offers a unique opportunity for studying and modeling the effects of specific
      gene defects on human liver development in vitro and for testing small molecules
      or other potential therapies for relevant liver disorders. Here we report, for
      the first time, the derivation of iPSCs by the retroviral transduction of
      Yamanaka's factors in serum and feeder-free culture conditions from liver
      specific patients with tyrosinemia, glycogen storage disease, progressive
      familial hereditary cholestasis, and two siblings with Crigler-Najjar syndrome.
      Furthermore, they were differentiated into functional hepatocyte-like cells
      efficiently. These iPSCs possessed properties of human embryonic stem cells
      (hESCs) and were successfully differentiated into three lineages that resembled
      hESC morphology, passaging, surface and pluripotency markers, normal karyotype,
      DNA methylation, and differentiation. The hepatic lineage-directed
      differentiation showed that the iPSC-derived hepatic cells expressed hepatocyte
      specific markers. Their functionality was confirmed by glycogen and lipid storage
      activity, secretion of albumin, alpha-fetoprotein, and urea, CYP450 metabolic
      activity, as well as LDL and indocyanin green uptake. Our results provide proof
      of principal that human liver-disease specific iPSCs present an exciting
      potential venue toward cell-based therapeutics, drug metabolism, human liver
      development and disease models for liver failure disorders.

PMID- 20821351
TI  - Vascular endothelial growth factor inhibitors in malignant gliomas.
AB  - Glioblastomas are highly vascularized tumors. Treatment strategies targeting
      angiogenesis have demonstrated promising results in preclinical studies and
      clinical trials in patients with malignant gliomas. Anti-VEGF agents, either
      alone or in combination with chemotherapy, have been associated with reduction in
      vasogenic brain edema, and prolonged progression-free survival. Larger
      prospective clinical trials are needed to validate these results, and to assess
      the impact of these agents on overall survival. Unfortunately, antiangiogenic
      treatment inevitably fails in most patients. Further studies are needed to
      understand the molecular pathways that enable a tumor to evade antiangiogenic
      therapy.

PMID- 20821353
TI  - Traumatic vasculogenic erectile dysfunction: role of penile microarterial bypass
      surgery.
AB  - Penile microarterial bypass surgery (MABS) may be the only treatment capable of
      restoring normal erectile function without necessity of chronic use of vasoactive
      medications or placement of a penile prosthesis. Lack of standardization in
      patient selection, hemodynamic evaluation, surgical technique, and limited long
      term outcome data using validated instruments has resulted in this surgery being
      considered experimental. In addition, poor reimbursements, long surgical time,
      and the need for microsurgical expertise have lead to infrequent penile
      revascularization procedures. Using the criteria for the Arterial Occlusive
      Disease Index patient, only 4 of 31 manuscripts met the criteria. The total
      studied population of these four publications was 50, which was considered too
      small to determine if MABS is effective or not. Reported successful outcomes were
      36% to 91%. We recently published the largest long-term outcome MABS study using
      validated instruments. We documented MABS provides long-term improvements in
      erectile function, depression, and overall satisfaction in well-selected
      patients. The Members of the Erectile Dysfunction Guideline Update Panel
      consider: "Arterial reconstructive surgery is a treatment option only in healthy
      individuals with recently acquired erectile dysfunction secondary to a focal
      arterial occlusion and in the absence of any evidence of generalized vascular
      disease."

PMID- 20821354
TI  - New concepts in the diagnosis and treatment of premature ejaculation.
AB  - Premature ejaculation is the most common male sexual dysfunction. The
      International Society of Sexual Medicine recently defined premature ejaculation
      as ejaculation less than about 1 min after penetration, inability to control
      ejaculation, and resulting negative personal consequences. Evolving treatments
      target the modulation of the neurobiological causes of the disorder. Current
      pharmaceuticals focus on aerosolized topical agents, selective serotonin reuptake
      inhibitors, 5-hydroxytryptamine receptor modulators, and opioid agonists. These
      emerging medications and the ability to tailor treatments based on genetic
      information likely will change the paradigm of this disorder and how it will be
      treated by clinicians.

PMID- 20821355
TI  - Overactive bladder and pain: management strategies.
AB  - Overactive bladder associated with pain (ie, interstitial cystitis/bladder pain
      syndrome [IC/BPS]) is a prevalent condition that can be very difficult to
      diagnose and even more difficult to treat. In this paper, we review the studied
      therapies for IC/BPS, including non-medication-based therapies, oral and
      intravesical-based medications, and surgical treatments for interstitial
      cystitis. We also review an approach to the treatment of a patient with IC/BPS
      using the previously published UPOINT clinical phenotyping template.

PMID- 20821356
TI  - Penile prosthesis infection: progress in prevention and treatment.
AB  - Almost four decades ago, modern penile implants were introduced as a treatment of
      erectile dysfunction. Infection associated with placement of an implant is a
      feared complication, and fortunately, has become less common due to a number of
      measures, including antibiotic-coated devices and chlorhexidine-alcohol skin
      preparation. When an infection around an implant occurs, the device should be
      removed. An option, termed a salvage (or rescue) procedure, is cleansing the
      wound with a series of antiseptic solutions and replacing a new prosthesis during
      the same procedure, with success in the range of 85%. The alternative is to
      return at a later date to replace the implant. However, the latter approach is
      associated with a difficult insertion, a shorter erection, and a less satisfied
      patient. Most patients elected the salvage approach because they were highly
      motivated to continue sexual activity to have the implant placed initially.

PMID- 20821357
TI  - Need for standardization in definition of success in clinical trials on stress
      urinary incontinence.

PMID- 20821358
TI  - Selection of ideal candidates for neuromodulation in refractory overactive
      bladder.
AB  - Sacral neuromodulation is a minimally invasive, reversible treatment option that
      has been approved by the US Food and Drug Administration for patients with
      urgency/frequency and urge incontinence. While long-term success rates are high,
      the high treatment cost and the need for operative revision or explantation in
      cases of failure make the selection of ideal candidates particularly important.
      Because predictive factors for success and the exact mechanism of action are not
      known, physicians must rely on a preimplantation test procedure, either in the
      office or in the operating room, to select patients for implantation of a pulse
      generator. In this paper, we review the recent literature on performing a test
      procedure with both temporary and permanent leads and the selection of optimal
      candidates for sacral neuromodulation therapy.

PMID- 20821359
TI  - Reverse modeling and solid free-form fabrication of sternum implant.
AB  - The paper presents a case where an implant for a part of the sternum (with costal
      cartilages) affected by cancer was created and implanted by using the specific
      reverse modeling method and solid free-form fabrication. The method provides
      surgeons with a fast and reliable tool for tissue engineering and implantation
      and therefore improves the quality of life for patients. Digital images of
      healthy sternum samples were used to develop a reverse modeling algorithm that
      semi-automatically generates a necessary and sufficient simplification of the
      tissue geometry to be fabricated in an inexpensive and applicable manner. In this
      particular case, the redesign of the missing part of the sternum in CAD software
      took three designer-hours. At the same time, the suitable simplification of the
      geometry affects the fabrication of simpler and less expensive casting molds.
      Furthermore, the core of the developed algorithm for the reverse modeling of
      sternum can be applied in the reverse modeling improvement of other tile (or
      plate-like) bones.

PMID- 20821360
TI  - Small-bowel capsule endoscopy diagnoses early and advanced neoplasms in
      asymptomatic patients with Lynch syndrome.
AB  - BACKGROUND AND STUDY AIMS: Patients with Lynch syndrome are at increased risk of
      developing small-bowel adenocarcinoma, which usually has a bad prognosis and
      needs to be diagnosed early. Our aim was to evaluate the yield of capsule
      endoscopy and CT enteroclysis in this situation. PATIENTS AND METHODS: We
      performed a prospective, blinded, comparative study of capsule endoscopy and CT
      enteroclysis in five academic centers. Thirty-five consecutive asymptomatic
      patients with Lynch syndrome, all with one proven deleterious mutation, were
      included. A double reading was performed blind for both types of examination.
      RESULTS: Histologically confirmed small-bowel neoplasms were diagnosed in three
      patients (8.6 %): one adenocarcinoma (T3N0M0) and two adenomas with low-grade
      dysplasia. Capsule endoscopy identified all neoplasms. CT enteroclysis raised
      suspicion of one neoplasm (adenocarcinoma) but missed the two others. Concordance
      between the two capsule readings was high with a kappa value of 0.78 (95 %CI 0.55
      to 1.0), which was not the case for CT enteroclysis, where the kappa value was
      0.15 (95 %CI -0.27 to 0.58). CONCLUSION: Curable early or advanced neoplasms in
      asymptomatic patients with Lynch syndrome using capsule endoscopy can be detected
      with a better reproducibility than with CT enteroclysis. The clinical usefulness
      of systematic small-bowel screening in these patients should be confirmed through
      large prospective studies.

PMID- 20821361
TI  - Brush cytology vs. endoscopic biopsy for the surveillance of Barrett's esophagus.
AB  - BACKGROUND AND STUDY AIMS: Periodic surveillance with systematic biopsies is
      recommended for patients with Barrett's esophagus. Brush cytology has been
      proposed as a simple inexpensive component of endoscopic surveillance, which may
      also detect abnormalities prior to detection of histologic abnormalities. The aim
      of the current study was to determine whether brush cytology provides any
      additional value over endoscopic surveillance biopsies in patients with Barrett's
      esophagus. PATIENTS: This retrospective cohort study included 530 patients with
      Barrett's esophagus undergoing endoscopic surveillance with paired biopsy and
      cytology specimens at the Cleveland Clinic between January 1994 and July 2008.
      The main outcome measures were sensitivity, specificity, and concordance rates of
      cytology and histology. RESULTS: Sensitivity of cytology for any dysplasia was 49
      % and specificity was 95 %. However, sensitivity was 82 % for detection of high
      grade dysplasia/adenocarcinoma but only 31 % for low grade/indefinite for
      dysplasia. The concordance rate between cytology and histology was 80 %.
      Histology had a higher dysplasia detection rate than cytology (24.0 % vs. 15.7 %,
      respectively; P <0.0001). CONCLUSIONS: Cytology has excellent specificity and
      good sensitivity for the detection of high grade dysplasia/adenocarcinoma but
      poor sensitivity for low grade dysplasia. There was substantial concordance
      between cytology and histology for the detection of dysplasia. However, histology
      had a higher dysplasia detection rate and therefore the value of routine cytology
      in the surveillance of Barrett's esophagus is questionable.

PMID- 20821363
TI  - Endoscopic retrograde cholangiopancreatography.

PMID- 20821364
TI  - [Bone tissue engineering for bone defect therapy].
AB  - In critical size bone defects resulting from failed fracture healing or
      pseudarthrosis surgery is usually required. In this context, autologous bone
      grafts and callus distraction represent the gold standard, while sometimes even
      vascularised bone transfer is mandatory including microsurgical techniques. The
      availability of donor sites for such procedures is limited and the resulting
      morbidity significant. Therefore, synthetic bone grafts have been developed as an
      alternative. They consist of a broad range of different materials such as natural
      and synthetic polymers, ceramic and compound materials, aiming to mimic the three
      dimensional character of autografts. In addition, they may act as a delivery
      vehicle for growth factors, antibiotics or cells. Their main limitation has been
      the lack of an intrinsic blood supply, limiting the potential for
      transplantation. This review provides an overview of matrices, cells and other
      therapeutic substances in the field of bone tissue engineering.

PMID- 20821362
TI  - A national survey of endoscopic mucosal resection for superficial
      gastrointestinal neoplasia.
AB  - BACKGROUND AND STUDY AIM: Studies on endoscopic mucosal resection (EMR) are
      mostly based on data from centers with high expertise. We report the average EMR
      results in a national survey of consecutive patients in France. METHODS: A 1-year
      survey was carried out to record immediate outcome data of all EMRs performed,
      regardless of lesion size or gastrointestinal location. RESULTS: Overall, 1335
      EMRs in 1210 patients were reported by 241 of the 736 gastroenterologists who
      performed such procedures (33 %). Resections were done for upper gastrointestinal
      lesions in 125 cases (41 esophageal, 43 gastric, and 41 duodenal lesions), in 45
      % of cases using specific EMR techniques such as ligation, cap, or traction. The
      technique for resecting the 1210 lower gastrointestinal lesions mostly consisted
      of saline-assisted polypectomy or EMR, with specific techniques used in only 2.2
      %. En bloc resection was less common with esophageal (46 %) or duodenal (54 %)
      neoplasms than in the lower gastrointestinal tract (73 %); size also had some
      influence (53 % > 1 cm vs. 92 % <=  1 cm). The overall complication rate was 5.2
      %; the rate was lower for lesions 1 cm or smaller (0.6 % vs. 4.6 %). Fifty-four
      early and 17 delayed complications were recorded, in 12 % of upper
      gastrointestinal and 4.6 % of colonic lesions. Surgery became necessary in 1.6 %
      for upper and 2.9 % for lower gastrointestinal neoplasms. No association was seen
      between physician EMR caseload and either en bloc resection rate or complication
      rate. CONCLUSIONS: EMR in general, especially saline-assisted polypectomy in the
      colon, appears to be reasonably safe even when performed by nonexperts. EMR for
      larger or for upper gastrointestinal lesions should probably be limited to high
      volume centers.

PMID- 20821365
TI  - [Significance of abdominal wall CT-angiography in planning DIEA perforator flaps,
      TRAM flaps and SIEA flaps].
AB  - Muscle sparing TRAM flaps and DIEA perforator flaps are standard procedures for
      breast reconstruction. Recently CT-angiography has been established to evaluate
      perforator vessels pre-operatively. CT-angiography was introduced to our
      department in July 2009. In a retrospective analysis data of the last 20 patients
      (altogether 22 flaps) before CT-angiography introduction and the following 20
      (also 22 flaps) patients after introduction of CT-angiography were analysed with
      regard to the ratio of TRAM to DIEP flaps, and the time required to raise the
      flaps. The same surgeon raised all flaps. As different surgeons performed
      dissection of the recipient site, anastomoses, and insertion of flaps, and
      patients received primary (with sentinel or complete lymphadenctomy) or secondary
      reconstructions, only the time required harvesting the flap was compared. Thus
      other influences on raising the flap were eliminated. DIEP flaps were harvested
      with one single perforator. If perfusion or was considered not to be safe via one
      single perforator a muscle sparing TRAM flap (ms2) was raised. Angiography was
      performed using a 64-slice multi-detector CT scanner. CT-angiography did not lead
      to an increased rate of DIEP flaps in relation to ms2-TRAM flaps. Harvesting time
      of all flap types with CT-angiography on average was 121 min, without CT
      angiography 135 min. This was not significantly different. However, separate
      analysis of DIEP flaps and ms2-TRAM flaps revealed a significant advantage of CT
      angiography based harvesting of DIEP flaps of 26 min: with CT-angiography 101 min
      vs. 127 min without CT-angiography (p<0.028). There were no significant
      differences for ms2-TRAM flaps. All scans showed course and branching, diameter
      and size of the inferior epigastric artery. If evident the superficial inferior
      epigastric artery (SIEA) was marked. Dosage was 292 mGy-606 mGy*cm dependent on
      body weight. CTDI was 6.8-14.7 mGy. CT-angiography is a reproducible and observer
      independent procedure that reliably demonstrates the inferior epigastric artery
      and its perforating branches. Sensitivity is considered to be 99,6%. Additionally
      the superficial inferior epigastric artery can be evaluated. In our patients the
      ratio of ms2-TRAM flaps to DIEP flaps was not affected by introducing CT
      angiography. However, DIEP flap harvesting was significantly accelerated.
      Harvesting of ms2-TRAM flaps was not affected. It remains to be seen whether the
      observed time advantage is really essential for this operation. Preoperative
      imaging of the perforators allows establishing a detailed, observable and
      comprehensible operation strategy, which particularly facilitates surgical
      training and learning of perforator dissection.

PMID- 20821366
TI  - Association study of energy homeostasis genes and antipsychotic-induced weight
      gain in patients with schizophrenia.
AB  - INTRODUCTION: Marked inter-individual variation has been observed with respect to
      the risk of weight gain and related metabolic disturbances during antipsychotic
      treatment, which in part could be explained by heritability. Such adverse effects
      have been proposed to occur through drug-induced mechanisms involving both the
      central nervous system and different peripheral tissues. METHODS: We genotyped
      tagSNPs in several genes ( ADIPOQ, PRKAA1, PRKAA2, PRKAB1, PRKAG1, PRKAG2,
      PRKAG3, FTO and FABP3) that regulate lipid and energy homeostasis for their
      possible association to antipsychotic-induced weight gain. RESULTS: In a sample
      of 160 patients of German origin with schizophrenia who had been monitored with
      respect to body weight, we found marked association between antipsychotic-related
      changes in BMI and 6 markers in the adiponectin gene ( ADIPOQ). DISCUSSION: These
      findings support previous observations (in patients' serum) that adiponectin is
      involved in antipsychotic-mediated metabolic adverse effects.

PMID- 20821367
TI  - Identifying patients with therapy-resistant depression by using factor analysis.
AB  - INTRODUCTION: Attempts to identify the factor structure in patients with
      treatment-resistant depression have been very limited. METHODS: Principal
      component analysis was performed using the baseline datasets from 3 add-on
      studies [2 with repetitive transcranial magnetic stimulation and one with
      transcranial pulsed electromagnetic fields (T-PEMF)], in which the relative
      effect as percentage of improvement during the treatment period was analysed.
      RESULTS: We identified 2 major factors, the first of which was a general factor.
      The second was a dual factor consisting of a depression subscale comprising the
      negatively loaded items (covering the pure depression items) and a treatment
      resistant subscale comprising the positively loaded items (covering lassitude,
      concentration difficulties and sleep problems). These 2 dual subscales were used
      as outcome measures. Improvement on the treatment resistant subscale was 40% in
      the active treatment group compared to 17-30% improvement in the sham treatments.
      DISCUSSION: It is possible to describe patients with therapy-resistant depression
      by a factor structure. Both rTMS and T-PEMF had a clinical effect on the factor
      derived scales when compared to sham treatment.

PMID- 20821368
TI  - D. R. Bach et al.: Elevated bilirubin in acute and transient psychotic disorder.
      Pharmacopsychiatry 2010; 43: 12-16.

PMID- 20821369
TI  - [Bet on that..?].

PMID- 20821371
TI  - Type II collagen-hyaluronan hydrogel--a step towards a scaffold for
      intervertebral disc tissue engineering.
AB  - Intervertebral disc regeneration strategies based on stem cell differentiation in
      combination with the design of functional scaffolds is an attractive approach
      towards repairing/regenerating the nucleus pulposus. The specific aim of this
      study was to optimise a composite hydrogel composed of type II collagen and
      hyaluronic acid (HA) as a carrier for mesenchymal stem cells. Hydrogel
      stabilisation was achieved by means of 1-ethyl-3(3-dimethyl aminopropyl)
      carbodiimide (EDC) and N-hydroxysuccinimide (NHS) cross-linking. Optimal hydrogel
      properties were determined by investigating different concentrations of EDC (8
      mM, 24 mM and 48 mM). Stable hydrogels were obtained independent of the
      concentration of carbodiimide used. The hydrogels cross-linked by the lowest
      concentration of EDC (8 mM) demonstrated high swelling properties. Additionally,
      improved proliferation of seeded rat mesenchymal stem cells (rMSCs) and hydrogel
      stability levels in culture were observed with this 8 mM cross-linked hydrogel.
      Results from this study indicate that EDC/NHS (8 mM) cross-linked type II
      collagen/HA hydrogel was capable of supporting viability of rMSCs, and
      furthermore their differentiation into a chondrogenic lineage. Further
      investigations should be conducted to determine its potential as scaffold for
      nucleus pulposus regeneration/repair.

PMID- 20821372
TI  - Biological responses of brushite-forming Zn- and ZnSr- substituted beta
      tricalcium phosphate bone cements.
AB  - The core aim of this study was to investigate zinc (Zn)- and zinc and strontium
      (ZnSr)-containing brushite-forming beta-tricalcium phosphate (TCP) cements for
      their effects on proliferation and differentiation of osteoblastic-like cells
      (MC3T3-E1 cell line) as well as for their in vivo behaviour in trabecular bone
      cylindrical defects in a pilot study. In vitro proliferation and maturation
      responses of MC3T3-E1 osteoblastic-like cells to bone cements were studied at the
      cellular and molecular levels. The Zn- and Sr-containing brushite cements were
      found to stimulate pre-osteoblastic proliferation and osteoblastic maturation.
      Indeed, MC3T3-E1 cells exposed to the powdered cements had increased
      proliferative rates and higher adhesiveness capacity, in comparison to control
      cells. Furthermore, they exhibited higher alkaline phosphatase (ALP) activity and
      increased Type-I collagen secretion and fibre deposition into the extracellular
      matrix. Proliferative and collagen deposition properties were more evident for
      cells grown in cements doped with Sr. The in vivo osteoconductive propertiesof
      the ZnCPC and ZnSrCPC cements were also pursued. Histological and
      histomorphometric analyses were performed at 1 and 2 months after implantation,
      using carbonated apatite cement (Norian SRS) as control. There was no evidence of
      cement-induced adverse foreign body reactions, and furthermore ZnCPC and ZnSrCPC
      cements revealed better in vivo performance in comparison to the control apatite
      cement. Additionally, the presence of both zinc and strontium resulted in the
      highest rate of new bone formation. These novel results indicate that the
      investigated ZnCPC and ZnSrCPC cements are both biocompatible and
      osteoconductive, being good candidate materials to use as bone substitutes.

PMID- 20821374
TI  - Interpretation of vicinal proton-proton coupling constants of heteroaromatic
      molecules in terms of topological electron density descriptors.
AB  - The indirect vicinal proton-proton coupling constants for pyrrole, furan,
      thiophene and 15 related heteroaromatic compounds were calculated using the Khon
      Sham approximation. An analysis of the four Ramsey contributions to the coupling
      constants was carried out showing that the Fermi contact term is always positive
      and dominant, although the remaining contributions have a nonnegligible net
      negative contribution. The trends observed for the proton-proton coupling
      constants were rationalized in terms of the properties of the electron density.
      It was found that electron delocalization between the corresponding hydrogen
      atoms plays a major role on the observed behavior with the charges of the carbon
      atoms bonded to them and the accompanying geometric variations being also of
      importance in the coupling mechanism.

PMID- 20821373
TI  - Feasibility study of a randomized controlled trial of a telephone-delivered
      problem-solving-occupational therapy intervention to reduce participation
      restrictions in rural breast cancer survivors undergoing chemotherapy.
AB  - OBJECTIVE: Breast cancer patients receiving adjuvant chemotherapy often
      experience functional effects of treatment that limit participation in life
      activities. The purpose of this study was to examine the feasibility of
      conducting a randomized controlled trial (RCT) of a novel intervention for these
      restrictions, determine acceptability of the intervention, and preliminarily
      assess its effects. METHODS: A pilot RCT of a telephone-delivered Problem-solving
      and Occupational Therapy intervention (PST-OT) to improve participation
      restrictions in rural breast cancer patients undergoing chemotherapy. Thirty-one
      participants with Stages 1-3 breast cancer were randomized to 6 weekly sessions
      of PST-OT (n = 15) and usual care (n = 16). The primary study outcome was the
      feasibility of conducting the trial. Secondary outcomes were functional, quality
      of life and emotional status as assessed at baseline, 6 and 12 weeks. RESULTS: Of
      46 patients referred 31 were enrolled (67% recruitment rate), of which 6
      participants withdrew (81% retention rate). Twenty-four participants completed
      all study-related assessments (77%). Ninety-two percent of PST-OT participants
      were highly satisfied with the intervention, and 92% reported PST-OT to be
      helpful/very helpful for overcoming participation restrictions. Ninety-seven
      percent of planned PST-OT treatment sessions were completed. Completion rates for
      PST-OT homework tasks were high. Measures of functioning, quality of life, and
      emotional state favored the PST-OT condition. CONCLUSION: This pilot study
      suggests that an RCT of the PST-OT intervention is feasible to conduct with rural
      breast cancer patients undergoing adjuvant chemotherapy and that PST-OT may have
      positive effects on function, quality of life, and emotional state.

PMID- 20821375
TI  - Fatigue and its correlates in cancer patients who had returned to work--a cohort
      study.
AB  - OBJECTIVES: Fatigue and other symptoms in cancer patients often interfere with
      social and occupational activities. Only a few studies, however, have examined
      relationship between fatigue and work-related outcomes. The aim of this study was
      to investigate which disease-related factors (treatment, diagnosis, cognitive
      dysfunction, depression, pain, and sleep disturbance) and work-related factors
      (work-load, work pressure, relationship to supervisor and colleagues, size of the
      company, and workplace accommodations) were related to fatigue in employed cancer
      survivors. METHODS: Data was collected by questionnaire at 6 months (baseline)
      and 18 months (end of the follow-up) after cancer diagnosis from 135 people with
      different types of cancer who had returned to work at follow-up. Fatigue was
      measured with a four-item sub-scale of MFI. Scores ranged from 4 to 20, with
      higher scores indicating more fatigue. RESULTS: The mean rate of general fatigue
      was 11.9 at baseline decreasing to 10.4 at the end of the follow-up (p<0.0001).
      At 6 months, higher work pressure (p = 0.02), physical workload (p<0.05) and less
      workplace accommodations (p = 0.03) were related to higher levels of fatigue.
      From disease-related factors, depression was associated with fatigue (p<0.0001)
      at baseline. Lack of workplace accommodations was the only factor affecting
      higher levels of fatigue at 18 months (p<0.001) and was also related to higher
      levels of depression at 6 months (p = 0.02) and at 18 months (p<0.001).
      CONCLUSIONS: Lack of workplace accommodations was significantly related to
      fatigue at the end of the follow-up, which suggests that accommodations for
      illness can help to reduce fatigue and depression.

PMID- 20821376
TI  - Measuring cancer patients' reasons for their information preference: construction
      of the Considerations Concerning Cancer Information (CCCI) questionnaire.
AB  - OBJECTIVES: This paper describes the further development and psychometric
      properties of an instrument to measure cancer patients' reasons to want complete
      or limited information: the Considerations Concerning Cancer Information
      questionnaire (CCCI). Understanding cancer patients' reasons to want complete or
      limited information will provide the physician with information that enables him
      or her to tailor information giving. METHODS: CCCI's content validity, internal
      structure, and convergent validity were investigated among 145 cancer patients,
      new to radiotherapy. RESULTS: Underlying reasons for information preference among
      cancer patients were derived from existing qualitative studies, narratives, and
      interviews. This resulted in the CCCI containing two parts: reasons to favor
      complete information disclosure and reasons to prefer only limited information
      about disease and treatment. The four identified dimensions to prefer information
      consist of: sense of control, expectations of others, anxiety, and autonomy. The
      four dimensions for reasons to give up on acquiring information consist of:
      avoidance, optimism, comprehension, and not wanting to be a burden. Confirmatory
      factor analysis indicated that the measurement model provided good fit to the
      data. Scales had good internal consistency, satisfactory item-total correlations
      corrected for overlap and satisfactory convergent validity. CONCLUSIONS: These
      findings confirm evidence of the reliability and validity of the CCCI for use in
      cancer care. Researchers and health-care providers can use the instrument to
      assess cancer patients' reasons to want complete or limited information and
      provide tailored care.

PMID- 20821377
TI  - The wish to hasten death: a review of clinical studies.
AB  - It is common for patients who are faced with physical or psychological suffering,
      particularly those in the advanced stages of a disease, to have some kind of wish
      to hasten death (WTHD). This paper reviews and summarises the current state of
      knowledge about the WTHD among people with end-stage disease, doing so from a
      clinical perspective and on the basis of published clinical research. Studies
      were identified through a search strategy applied to the main scientific
      databases. Clinical studies show that the WTHD has a multi-factor aetiology. The
      literature review suggests-perhaps in line with better management of physical
      pain-that psychological and spiritual aspects, including social factors, are the
      most important cause of such a wish. One of the difficulties facing clinical
      research is the lack of terminological and conceptual precision in defining the
      construct. Indeed, studies frequently blur the distinction between a generic wish
      to die, a WTDH (whether sporadic or persistent over time), the explicit
      expression of a wish to die, and a request for euthanasia or physician-assisted
      suicide. A notable contribution to knowledge in this field has been made by
      scales designed to evaluate the WTHD, although the problems of conceptual
      definition may once again limit the conclusions, which can be drawn from the
      results. Studies using qualitative methodology have also provided new information
      that can help in understanding such wishes. Further clinical research is needed
      to provide a complete understanding of this phenomenon and to foster the
      development of suitable care plans.

PMID- 20821378
TI  - Predicting the 1H and 13C NMR spectra of paramagnetic Ru(III) complexes by DFT.
AB  - Nuclear shieldings, including the Fermi-contact and pseudocontact terms, have
      been calculated with density functional theory (DFT) (nonrelativistic and
      relativistic) methods in several Ru(III) complexes, thereby predicting (1)H and
      (13)C paramagnetic shifts. A fair agreement with experimental values is observed.
      Structural, magnetic and dynamic parameters have also been input to the Solomon
      Bloembergen equation in order to predict signal lineshapes. It is shown that DFT
      predicted paramagnetic shifts can greatly aid in obtaining and understanding NMR
      spectra of paramagnetic Ru(III) complexes.

PMID- 20821379
TI  - Dose-dependent inhibition of transporter-mediated hepatic uptake and biliary
      excretion of methotrexate by cyclosporine A in an isolated perfused rat liver
      model.
AB  - Methotrexate (MTX) and cyclosporine (CyA) are coadministered in a number of
      diseases. In this study, the effects of CyA on the hepatobiliary disposition of
      MTX were investigated in an isolated perfused rat liver model. A bolus 5-mg dose
      of MTX was added to a recirculating perfusate in the absence or presence of a
      relatively low (0.5 mg) or high (2.5 mg) dose of CyA or vehicle pretreatment, and
      perfusate, bile, and terminal liver samples were collected for analysis by high
      performance liquid chromatography (HPLC). In control and vehicle groups, MTX
      showed a low hepatic extraction ratio (~0.1) and was almost completely eliminated
      by excretion into the bile. The low-dose CyA significantly reduced (60%) the
      hepatic extraction ratio and clearance of MTX, without affecting the bile/liver
      concentration ratio, suggesting inhibition of sinusoidal uptake of MTX only. In
      contrast, the high-dose CyA significantly reduced both hepatic uptake and Mrp2
      mediated biliary excretion of MTX. Isolated rat hepatocyte uptake studies showed
      significant inhibition of [(3)H]MTX uptake in the presence of CyA. It is
      concluded that CyA significantly alters the hepatobiliary disposition of MTX by
      inhibiting its sinusoidal uptake and/or biliary transport, potentially reducing
      enterohepatic recirculation of the drug in vivo.

PMID- 20821380
TI  - Semi-automated protein binding methodology using equilibrium dialysis and a novel
      mixed-matrix cassette approach.
AB  - A semi-automated protein binding assay using equilibrium dialysis (ED) and a
      novel mixed-matrix methodology has been developed. This method decreases mass
      spectrometer run time and reduces the likelihood of experimental artifacts. In
      this cassette-based approach, a single matrix is prepared following dialysis by
      mixing dialyzed plasma and buffer containing different test compounds from the
      same dialysis plate. This approach differs from the traditional mixed-matrix
      method where fresh plasma and fresh buffer are mixed with opposing dialyzed
      samples. This new mixed-matrix methodology is compatible with various high
      throughput ED and ultrafiltration devices, many liquid handling systems, and can
      be used for plasma, serum, albumin, alpha-1 acid glycoprotein, microsomal, and
      fine tissue homogenate binding studies. The utility of the method can be further
      enhanced by varying the number of replicates, concentrations, and matrices with
      simple modifications. Using 29 structurally diverse marketed drugs with a wide
      range of protein binding values reported in the literature, we have shown the new
      procedure reduces the total number of samples by nearly half compared to
      traditional methods, eliminates the need for standard curves, and increases the
      uniformity of the sample matrix for LC/MS/MS analysis.

PMID- 20821381
TI  - A novel controlled release drug delivery system for multiple drugs based on
      electrospun nanofibers containing nanoparticles.
AB  - This study describes development of a novel controlled drug release system for
      multiple drugs, it consisted of Chitosan nanoparticles/PCL composite electrospun
      nanofibers with core-sheath structures. Two model agents' rhodamine B and
      naproxen were successfully loaded in the core and sheath region respectively. The
      behavior of these two agents demonstrated a good controlled release and
      temporality, providing a new way to obtain program or temporality release for
      multiple agents. Particularly, this is potential applications in the field of
      tissue engineering, sutures and wound dressings.

PMID- 20821382
TI  - Factors affecting the viscosity in high concentration solutions of different
      monoclonal antibodies.
AB  - The viscosity profiles of four different IgG(1) molecules were studied as a
      function of concentration at pH 6.0. At high concentrations, MAb-H and -A showed
      significantly higher viscosities as compared to MAb-G and -E. Zeta Potential (xi)
      measurements showed that all the IgG(1) molecules carried a net positive charge
      at this pH. MAb-G showed the highest positive zeta potential followed by MAb-E, 
      H, and -A. A consistent interpretation of the impact of net charge on viscosity
      for these MAbs is not possible, suggesting that electroviscous effects cannot
      explain the differences in viscosity. Values of k(D) (dynamic light scattering)
      indicated that the intermolecular interactions were repulsive for MAb-E and -G;
      and attractive for MAb-H and -A. Solution storage modulus (G') in high
      concentration solutions was consistent with attractive intermolecular
      interactions for MAb-H and -A, and repulsive interactions for MAb-G and -E.
      Effect of salt addition on solution G' and k(D) indicated that the interactions
      were primarily electrostatic in nature. The concentration dependent viscosity
      data were analyzed using a modified Ross and Minton equation. The analysis
      explicitly differentiates between the effect of molecular shape, size, self
      crowding, and electrostatic intermolecular interactions in governing high
      concentration viscosity behavior.

PMID- 20821383
TI  - Curcumin-loaded hydrogel nanoparticles: application in anti-malarial therapy and
      toxicological evaluation.
AB  - The present investigation involved preparation of hydrogel nanoparticles using a
      combination of hydroxyl propyl methyl cellulose and polyvinyl pyrrolidone. The
      objective was to exploit the size and hydrophilic nature of the formulated
      nanocarriers to enhance absorption and prolong the rapid clearance of curcumin
      due to possible evasion of the reticulo-endothelial system. Reproducible
      nanoparticles of size around 100 nm, a fairly narrow distribution and
      encapsulation efficiency of 72%, were produced by the solvent emulsion
      evaporation technique. This optimized system was further subjected to freeze
      drying. The freeze-dried product was readily reconstituted with distilled water.
      The reconstituted product exhibited a size and distribution similar to that
      before freeze-drying, drug content of greater than 99% and presence of amorphous
      drug when analyzed by differential scanning calorimetry (DSC) which may result in
      possible improved absorption of curcumin. In vivo anti-malarial studies revealed
      significant superior action of nanoparticles over curcumin control suggesting the
      possibility of the formulation being employed as an adjunct anti-malarial therapy
      along with the standard therapy. Acute and subacute toxicity studies confirmed
      the oral safety of the formulation. A battery of genotoxicity studies was
      conducted to evaluate the nongenotoxic potential of the developed formulation
      thus indicating the possibility of the formulation being employed for prolonged
      duration.

PMID- 20821384
TI  - Fast and accurate analysis of drugs using amperometry associated with flow
      injection analysis.
AB  - This review presents a general overview about the amperometric detection
      potentialities associated to flow injection analysis (FIA). Fundamental aspects,
      developments, applications and advantages accrued from the coupling of
      voltammetry with FIA for pharmaceutical analyses are discussed. The selected
      references present several examples for this association in various classes of
      drugs and support their advantages. Examples illustrate that the amperometric
      techniques coupled with flow system can usually be used in drug routine analysis
      without sample pretreatment. Amperometry/FIA has proved to be an excellent
      alternative to the chromatographic techniques and it has been used in routine
      analysis, from the simplest analytes to more complex species, solving even
      special cases such as the enantiomeric analysis of pharmaceutical compounds with
      a chiral moiety, which requires time-consuming sample preparation or expensive
      instrumentation. This revision also aims to contribute for reducing the gap
      between the vast possibilities enabled by electroanalytical techniques and their
      effective utilization for pharmaceutical analysis.

PMID- 20821385
TI  - Development of PLGA nanoparticles simultaneously loaded with vincristine and
      verapamil for treatment of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the malignant tumors with poor chemo
      sensitivity to vincristine sulfate (VCR) due to multi-drug resistance (MDR).
      Combinations of encapsulated VCR and verapamil hydrochloride (VRP, a chemo
      sensitizer) might be a potential strategy to improve HCC therapeutic efficacy of
      VCR. PLGA nanoparticles (PLGANPs) simultaneously loaded with VCR and VRP (CVn)
      were prepared. The entrapment efficiencies of VCR and VRP were 70.92 +/- 3.78%
      and 85.78 +/- 3.23%, respectively (n = 3). The HCC therapeutic activity of CVn
      was assessed using MTT assay. In BEL7402 and BEL7402/5-FU human hepatocarcinoma
      cell lines, CVn had the same antitumor effect as one free drug/another agent
      loaded PLGANPs (C + Vn or Cn + V) combination and coadministration of two single
      agent-loaded PLGANPs (Cn + Vn), which was slightly higher than that of the free
      VCR/VRP combination (C - V). CVn might cause lower normal tissue drug toxicity by
      the enhanced permeation and retention effect in vivo. Additionally, CVn might
      cause fewer drug-drug interaction and be the most potential formulation to
      simultaneously deliver VCR and VRP to the target cell in vivo than the other
      three nanoparticle formulations (C + Vn, Cn + V, and Cn + Vn). Therefore, we
      speculate that CVn might be the most effective preparation in the treatment of
      drug-resistant human HCC in vivo.

PMID- 20821386
TI  - Transmembrane delivery and biological effect of human growth hormone via a phage
      displayed peptide in vivo and in vitro.
AB  - For a long time, people have been looking forward to being able to clinically
      deliver bio-drugs systemically by a noninvasive method. Here, we show that a
      synthetic peptide, TD (ACSSSPSKHCG) was efficient in transferring human growth
      hormone (GH) across various kinds of membranes and the blood-brain barrier (BBB)
      in vivo via rectal administration, resulting in elevation of GH level in serum,
      acetylcholine and O-choline acetyltransferase activities and GH /IGF-1 contents
      in brain tissues, manifesting great therapeutic effects on chronic age-related
      dementia in mice and ameliorating neuronal damage in the brain. Furthermore, the
      effects of Abeta and TD/GH on LDH release, apoptosis and its relevant gene
      expression, involving bcl-2 and bax/caspase-3, were observed in a human
      neuroblastoma cell line (SH-SY5Y). Results indicated that GH decreased LDH
      release, apoptosis, and bax/caspase-3 activity, and increased bcl-2 expression
      compared with Abeta treatment, moreover, TD/GH may enhance the effects due to
      existence of TD, which might be dependent on TD assisted cross-membrane delivery
      of GH. The transdermal/transmembrane-enhancing activity of the TD peptide was
      also manifested on porcine abdominal skin in vivo and the murine embryonic
      fibroblast cell line (3T3 cell) in vitro, which was further shown through
      interaction between TD and lecithin (one constituent of the cell membrane) by ESI
      MS. In conclusion, TD/GH counteracted brain defects in aged mice in vivo and cell
      apoptosis induced by Abeta in vitro might explain several underlying mechanisms
      by which GH could ameliorate learning and memory deficits in aged mice. Mixed
      TD/GH transmembrane delivery might be a promising therapy of Alzheimer's disease.

PMID- 20821387
TI  - Prodrugs: Some thoughts and current issues.
AB  - The prodrug approach to resolving formulation, delivery, and toxicity limitations
      on problematic drugs has had its proponents and detractors. Over the last 10
      years or so, about 20% of all new small molecule NCEs have been prodrugs-a number
      that will surprise some. As chemists begin to explore new chemical spaces, larger
      and more complex molecules present greater drug delivery challenges. Prodrugs
      provide a means of solving these challenges, but also have their limitations.
      Prodrugs are becoming an integral part of the drug discovery paradigm in some
      large pharma companies, and a number of small biotech companies have been built
      around the design and application of prodrugs to improve drug candidates. Some
      issues facing the area of prodrug research and the commercialization of prodrugs
      are discussed.

PMID- 20821388
TI  - Effects of cogrinding with beta-cyclodextrin on the solid state fentanyl.
AB  - Fentanyl base and beta-cyclodextrin (beta-CD) were coground at 1:1 and 1:2 molar
      ratios (fentanyl: beta-CD) and the physicochemical characteristics of the
      mixtures were studied using differential scanning calorimetry (DSC), Fourier
      transform infrared spectroscopy (FTIR), solid state (13)C nuclear magnetic
      resonance (NMR) spectroscopy and powder X-ray diffraction (PXRD) measurement.
      Additionally, portions of the coground samples were exposed to high relative
      humidity to investigate fentanyl and beta-CD interactions. The results of DSC and
      PXRD analyses indicate that the ground mixtures are in an amorphous state, and
      the FTIR measurements show hydrogen bonding interactions between fentanyl and
      beta-CD. Solid state (13)C NMR indicates that a fentanyl/beta-CD inclusion
      compound is formed in the humidified mixture. Furthermore, PXRD data from the
      humidified mixtures are similar to the PXRD patterns from the inclusion complex.

PMID- 20821389
TI  - Comparative effects of pH and ionic strength on protein-protein interactions,
      unfolding, and aggregation for IgG1 antibodies.
AB  - Changes in protein-protein interactions, protein unfolding, and nonnative
      aggregation were assessed for a series of human IgG1 antibodies as a function of
      pH and solution ionic strength (I). Unfolding transitions were characterized with
      differential scanning calorimetry. Protein-protein interactions were
      characterized with the apparent second virial coefficient (A(2)) from light
      scattering. Aggregation pathways were assessed using size-exclusion
      chromatography and multi-angle laser light scattering, aggregation kinetics, and
      structural changes monitored by circular dichroism spectroscopy and thioflavine T
      (ThT) binding. Ionic strength had relatively minor qualitative effects on
      unfolding, while pH had large effects for all four antibodies. A(2) was sensitive
      to both pH and I, and indicated that electrostatic interactions and nonuniform
      surface-charge distributions were important near neutral pH. Depending on
      solution pH and I, distinct aggregation pathways were found for each antibody,
      and these shared similar patterns versus pH, I, and A(2). Main differences
      observed across different antibodies included thermal unfolding transitions in
      DSC and the effects of pH and I on aggregation kinetics and pathways. These
      correlated strongly with whether aggregates of a given antibody bound ThT,
      suggesting possible differences with respect to conformational changes and/or
      regions of the proteins that are structurally involved in stabilizing the
      aggregates.

PMID- 20821390
TI  - The developability classification system: application of biopharmaceutics
      concepts to formulation development.
AB  - A revised classification system for oral drugs was developed using the
      biopharmaceutics classification system (BCS) as a starting point. The revised
      system is designed to have a greater focus on drug developability. Intestinal
      solubility, the compensatory nature of solubility and permeability in the small
      intestine and an estimate of the particle size needed to overcome dissolution
      rate limited absorption were all considered in the revised system. The system was
      then validated by comparison with literature on the in vivo performance of a
      number of test compounds. Observations on the test compounds were consistent with
      the revised classification, termed the developability classification system
      (DCS), showing it to be of greater value in predicting what factors are critical
      to in vivo performance than the widely used BCS.

PMID- 20821391
TI  - Synthesis and characterization of chitosan hydrogels containing 5-aminosalicylic
      acid nanopendents for colon: specific drug delivery.
AB  - The main aim of this research was to develop and evaluate a multiparticulate
      system of Ac-poly(amidoamine)(PAMAM)(G4)-chitosan (CS) hydrogels exploiting pH
      sensitive and specific biodegradability properties for colon-targeted delivery of
      5-aminosalicylic acid (5-ASA). All formulations were evaluated for particle size,
      encapsulation efficiency, swellability, and in vitro drug release. The size of
      the hydrogel was found to nanorange. The integrity of 5-ASA in the release
      fraction was assessed using sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The CS-Ac-PAMAM hydrogel was developed based on the modulation
      of ratio show promise as a system for controlled delivery of drug.

PMID- 20821392
TI  - Thiol-disulfide interchange in the tocinoic acid/glutathione system during
      freezing and drying.
AB  - Thiol-disulfide interchange ("disulfide scrambling") is a common mechanism of
      covalent aggregation for protein drugs. Using tocinoic acid (cyclo-S-Cys-Tyr-Ile
      Gln-Asn-Cys-(S); TA(ox)) and glutathione (gammaGlu-Cys-Gly; GSH), our previous
      work demonstrated that thiol/disulfide interchange is affected by lyophilization
      in a manner consistent with irreversible and regioselective loss of TA(ox) (Zhang
      et al., 2009, J Pharm Sci 98/9: 3312-3318). Here, we explore the contributions of
      stages of the lyophilization cycle to perturbations in thiol/disulfide
      interchange in the TA/GSH system. TA(ox) and GSH were co-lyophilized from
      phosphate buffer in the presence or absence of various excipients, then analyzed
      for TA(ox) and mixed disulfide products by reverse phase high performance liquid
      chromatography (rp-HPLC). Perturbations were found to occur primarily during
      freezing, before significant amounts of ice were removed by sublimation. Addition
      of a lyoprotectant (sucrose), a cryoprotectant (Tween-20) and flash-freezing
      influenced the product distribution only while ice was still present. Decreasing
      the redox potential by the addition of oxidized glutathione (GSSG) affected the
      product distribution differently in lyophilized samples and solution controls,
      but in neither case led to increased conservation of TA(ox).

PMID- 20821393
TI  - Investigation of Metformin HCl lot-to-lot variation on flowability differences
      exhibited during drug product processing.
AB  - The purpose of this study was to determine the cause for flowability difference
      observed during drug product processing when different Metformin HCl drug
      substance batches of varying age were used. It was found that the lead time (age)
      between the final step (milling) in the manufacturing process of the Metformin
      HCl drug substance could be a factor. The lead time had an impact on flowability
      of Metformin/excipient blends during drug product processing even though these
      batches had no apparent differences in their release specifications. To study and
      understand the aging effect, two batches of Metformin HCl manufactured at
      different periods of time were selected. The surface energy values obtained by
      the density functional theory (DFT) method together with X-ray diffraction
      patterns, thermally stimulated current measurements, and dynamic vapor sorption
      isotherms indicated that the freshly manufactured Metformin HCl material contains
      detectable amounts of surface crystal defects, but are absent in aged sample,
      which could be the cause of flowability differences of Metformin/excipient blends
      observed during the drug product processing. Having identified the cause for
      different flow behavior, a method to destroy these defects was designed and the
      issue was resolved by rapid aging of Metformin HCl under humidity at room
      temperature.

PMID- 20821394
TI  - The influence of averaging procedure on the accuracy of IVIVC predictions:
      immediate release dosage form case study.
AB  - In vivo-in vitro correlation (IVIVC) is an effective tool to predict absorption
      behavior of active substances from pharmaceutical dosage forms. The model for
      immediate release dosage form containing amoxicillin was used in the presented
      study to check if the calculation method of absorption profiles can influence
      final results achieved. The comparison showed that an averaging of individual
      absorption profiles performed by Wagner-Nelson (WN) conversion method can lead to
      lose the discrimination properties of the model. The approach considering
      individual plasma concentration versus time profiles enabled to average
      absorption profiles prior WN conversion. In turn, that enabled to find
      differences between dispersible tablets and capsules. It was concluded that in
      the case of immediate release dosage form, the decision to use averaging method
      should be based on an individual situation; however, it seems that the influence
      of such a procedure on the discrimination properties of the model is then more
      significant.

PMID- 20821396
TI  - Pharmaceutical applications of separation of absorption and scattering in near
      infrared spectroscopy (NIRS).
AB  - The number of near-infrared (NIR) spectroscopic applications in the
      pharmaceutical sciences has grown significantly in the last decade. Despite its
      widespread application, the fundamental interaction between NIR radiation and
      pharmaceutical materials is often not mechanistically well understood. Separation
      of absorption and scattering in near-infrared spectroscopy (NIRS) is intended to
      extract absorption and scattering spectra (i.e., absorption and reduced
      scattering coefficients) from reflectance/transmittance NIR measurements. The
      purpose of the separation is twofold: (1) to enhance the understanding of the
      individual roles played by absorption and scattering in NIRS and (2) to apply the
      separated absorption and scattering spectra for practical spectroscopic analyses.
      This review paper surveys the multiple techniques reported to date on the
      separation of NIR absorption and scattering within pharmaceutical applications,
      focusing on the instrumentations, mathematical approaches used to separate
      absorption and scattering and related pharmaceutical applications. This
      literature review is expected to enhance the understanding and thereby the
      utility of NIRS in pharmaceutical science. Further, the measurement and
      subsequent understanding of the separation of absorption and scattering is
      expected to increase not only the number of NIRS applications, but also their
      robustness.

PMID- 20821395
TI  - Triggering liposomal drug release with a lysosomotropic agent.
AB  - Drug release from liposomes in the endosome-lysosomal organelles into cytoplasm
      is critical to cytotoxicity and anticancer effects. Chloroquine is a
      lysosomotropic agent that has been reported to enhance in vitro cytotoxicity of
      basic anticancer drugs. To investigate the mechanism of chloroquine triggering
      basic anticancer drugs release from liposomes and the potential to treat solid
      tumors in clinic, daunorubicin was loaded into folate-targeted liposomes by
      ammonium sulfate remote loading method. In vitro triggered release profiles
      showed that chloroquine can instantly expel about 11% daunorubicin out of
      liposomes. In vitro cytotoxicity of folate-targeted liposomal daunorubicin on
      L1210JF(FR+) was enhanced by chloroquine, which was further confirmed by confocal
      micrographs. Intraliposomal pH was increased by adding chloroquine into 8
      hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) liposomes with
      ammonium sulfate gradient, but was not higher than 5.5. Ion exchange and pH
      rising are the most plausible mechanisms of chloroquine triggering daunorubicin
      release from liposomes. In vivo anticancer effects on a murine solid tumor model
      with L1210JF indicated that chloroquine induced daunorubicin release from
      liposomes as well. Overall, these results support the potential application of
      chloroquine to trigger the release of liposomal drugs and ultimately to improve
      the therapeutic efficacy.

PMID- 20821397
TI  - Risk assessment and physicochemical characterization of a metastable dihydrate
      API phase for intravenous formulation development.
AB  - (1S,5R)-2-{[(4S)-azepan-4-ylamino]carbonyl}-7-oxo-2,6-diazabicyclo[3.2.0] heptane
      6-sulfonic acid (Compound 1) is a beta-lactamase inhibitor for intravenous
      administration. The objective of this preformulation study was to determine the
      most appropriate form of the API for development. Compound 1 can exist as an
      amorphous solid and four distinct crystalline phases A, B, C, and D in the solid
      state. Slurry experiments along with analysis of physicochemical properties were
      used to construct a phase diagram and select the most suitable form of the API
      for development. In aqueous formulations, the dihydrate form of the API was
      predominant and, due to the more favorable solubility and dissolution profile
      required for preclinical and clinical studies, a metastable form of the API was
      selected, and the risks associated with developing this form were evaluated.

PMID- 20821398
TI  - Pathoanatomy of posterior ankle impingement in ballet dancers.
AB  - Dance is a high performance athletic activity that leads to great numbers of
      injuries, particularly in the ankle region. One reason for this is the extreme
      range of ankle motion required of dancers, especially females in classical ballet
      where the en pointe and demi-pointe positions are common. These positions of
      maximal plantar flexion produce excessive force on the posterior ankle and may
      result in impingement, pain, and disability. Os trigonum and protruding lateral
      talar process are two common and well-documented morphological variations
      associated with posterior ankle impingement in ballet dancers. Other less well
      known conditions, of both bony and soft tissue origins, can also elicit symptoms.
      This article reviews the anatomical causes of posterior ankle impingement that
      commonly affect ballet dancers with a view to equipping healthcare professionals
      for improved effectiveness in diagnosing and treating this pathology in a unique
      type of athlete.

PMID- 20821399
TI  - Nasal, sellar, and sphenoid sinus measurements in relation to pituitary surgery.
AB  - A study of 24 adult Caucasian cadavers was undertaken to assess and document the
      anatomical measurements within the nasal cavity and sphenoid sinus as routes of
      instrumentation utilized in sublabial transsphenoidal and endonasal endoscopic
      approaches. Five measurements were performed. The mean thickness of the anterior
      sellar wall was 0.8 +/- 0.3 mm for both the sellar and presellar types of
      sinuses, respectively. Also, the mean thickness of the bony floor of the sellar
      type of sinus was 0.9 +/- 0.4 mm. In addition, the mean depth of the sphenoid
      sinus was 13.6 +/- 5.1 mm for the sellar type and 13.2 +/- 3.9 mm for the
      presellar type of sinus. Furthermore, the mean distance between the suspinale
      (inferior-posterior edge of the anterior nasal spine) and the anterior sphenoid
      wall was 62.3 +/- 4.6 mm for the sellar type of sinus (P < 0.05) and 60.6 +/- 2.9
      mm for the presellar type of sinus, while the distance between the subspinale and
      the anterior sellar wall had a mean value of 75.9 +/- 6.3 mm for the sellar type
      of sinus (P < 0.05) and 73.8 +/- 4.2 mm for the presellar type of sinus, with the
      distance of the sellar type sinus being greater for male specimens. Sphenoid
      sinus pneumatization was of a conchal type in 4%, presellar type in 28%, and
      sellar type in 68% of subjects examined. The results of the current study expand
      upon current anatomical knowledge and may be beneficial in the future refinement
      of surgical instrument design.

PMID- 20821400
TI  - Findings of unique small muscle fibers at the superficial portion of the
      orbicularis oculi in the lateral canthal region of Japanese adult cadavers.
AB  - This study reports the existence of previously unknown muscle fascicles in
      Japanese adult cadavers. A bundle of these muscle fascicles diverged from the
      pretarsal portion of the orbicularis oculi muscle and coursed in a lateral
      direction superficial to this muscle. When observed with the naked eye, the
      bundle seemed to originate at the medial canthus and run along or near the edge
      of the upper eyelid. However, its boundary with the orbicularis oculi muscle was
      indistinguishable until it crossed superficial to this muscle. Throughout our
      observations, the thin muscle bundle was identified with high frequency (94%, 49
      of 52 individual cadavers), and is thus unlikely to be an artifact. Light
      microscopy revealed that, in sagittal sections, the thin muscle bundle was
      located on the superficial side of the lateral portion of the orbicularis oculi
      muscle, while in horizontal sections, it ran in a superficial plane to the
      orbicularis oculi muscle in a medial to lateral direction. Despite having some
      similarity to a muscular raphe, the lateral canthal band, and to one of the
      previously known inferior muscles of the orbicularis oculi muscle, the results of
      our anatomical study suggest that the bundle is none of these. Rather, it is a
      previously unreported muscle that likely contributes to the surface morphology at
      the lateral canthus.

PMID- 20821401
TI  - Morphological study of the fetal parotid duct and buccinator muscle and the
      relationship to salivary secretion.
AB  - The parotid glands secrete about 25% of all saliva produced. In the presence of a
      stimulus, the amount of saliva secreted from the parotid gland increases to 50%.
      A decrease in the amount of produced saliva due to aging and parotiditis results
      in a dry mouth. Therefore, the parotid duct is important to maintaining a healthy
      oral cavity. In human adults, the parotid duct, approximately 6-8-cm long,
      travels over the masseter muscle and penetrates the buccinator muscle to enter
      the oral cavity. Although there have been various studies regarding the parotid
      gland, only few suggest a functional role of the parotid duct, especially its
      area of penetration of the buccinator muscle. In this study, 34 fetal specimens
      ranging from 4 to 10 months of age at death were dissected for anatomical and
      histological examinations. The area of the parotid duct penetrating the
      buccinator muscle was fully formed in 5-month-old fetuses. This study found
      buccinator muscle fibers invading the parotid duct wall near its opening in 6
      month-old fetuses and older. Our results support the claim that the buccinator
      muscle may act as a sphincter, playing a role in regulating and possibly
      preventing the reflux of salivary secretions into the parotid duct.

PMID- 20821402
TI  - Human laryngeal ganglia contain both sympathetic and parasympathetic cell types.
AB  - The presence of ganglia associated with the laryngeal nerves is well documented.
      In man, these ganglia have been less well studied than in other species and, in
      particular, the cell types within these ganglia are less well characterized.
      Using a panel of antibodies to a variety of markers found in the paraganglion
      cells of other species, we were able to show the existence of at least two
      populations of cells within human laryngeal paraganglia. One population contained
      chromogranin and tyrosine hydroxylase representing a neurosecretory population
      possibly secreting dopamine. A second population of choline acetyltransferase
      positive cells would appear to have a putative parasympathetic function. Further
      work is needed to characterize these cell populations more fully before it will
      be possible to assign functions to these cell types but our results are
      consistent with the postulated functions of these ganglia as chemoreceptors,
      neurosecretory cells, and regulators of laryngeal mucus secretion.

PMID- 20821403
TI  - The arterial supply of the long head of biceps tendon: Anatomical study with
      implications for tendon rupture.
AB  - Zones of hypovascularity are thought to exist in several tendons of the shoulder,
      contributing to localized tendon weakness and subsequent rupture in clinical
      practice. Although these zones have been demonstrated in many frequently ruptured
      tendons, the existence of a similar area in the often ruptured long head of
      biceps (LHB) tendon is largely unknown. Twenty cadaveric upper limb specimens
      were dissected after injection with either a radio-opaque lead oxide/milk mixture
      or India ink, followed by histological sectioning of the tendons. The LHB tendon
      was consistently supplied via its osteotendinous and musculotendinous junctions
      by branches of the thoracoacromial and brachial arteries respectively. In two
      specimens, additional branches from the anterior circumflex humeral artery
      travelling in a mesotenon vascularized the midsection of tendon. These source
      arteries divided the LHB tendon into either two or three vascular territories,
      depending upon the presence of the mesotenon-derived vascular supply. A zone of
      hypovascularity was consistently found in the region of the LHB tendon most
      frequently prone to rupture. This zone covered an area 1.2-3 cm from the tendon
      origin, extending from midway through the glenohumeral joint to the proximal
      inter-tubercular groove. This hypovascular region occurred on the border of two
      adjacent vascular territories, where reduced caliber choke vessels provide
      limited arterial supply. While it is probable that the limited arterial supply
      contributes to the susceptibility of this area to rupture, similar to other
      tendons the true pathogenesis is likely to be a combination of both vascular and
      mechanical factors.

PMID- 20821404
TI  - Microanatomical and immunohistochemical study of the human lateral antebrachial
      cutaneous nerve of forearm at the antecubital fossa and its clinical
      implications.
AB  - Changes in the intraneural anatomy with age can cause poor prognosis of nerve
      repair in patients after nerve injury. The occurrence of Complex Regional Pain
      Syndrome-Type II, secondary to peripheral nerve injury, is common. The purpose of
      this study is to asses changes in cross-sectional anatomy of the lateral
      antebrachial cutaneous nerve of forearm (LCNF) at the antecubital fossa in the
      fascicular, nonfascicular components (adipose and nonadipose tissue), and
      sympathetic fibers area with respect to age. For the purpose of the study, 32
      human (37-88 years) fresh cadaveric LCNF were collected from left-antecubital
      fossae and processed for histological, morphometric analysis [total cross
      sectional (Asc), fascicular (Af), and nonfascicular area (Anonf)], and
      immunohistochemical method (tyrosine hydroxylase) for sympathetic fibers. The
      LCNF's average total cross-sectional area was 3.024 mm(2), and fascicular area
      was 0.582 mm(2). The average number of fascicles per mm(2) was 3.09. The cross
      sectional area in the nerve was mainly occupied by nonfascicular connective
      tissue (80.75%). There was increased adipose tissue deposition (48.48% of Asc)
      and decreased collagen fibers (32.24% of Asc) in interfascicular domains without
      any definite relationship with age. The average sympathetic fiber area was 0.026
      mm(2) within the nerve fascicular area without any correlation with age. In LCNF,
      there was more adipose tissue and less collagen fibers deposition in the
      interfascicular domains of all age cases, and this may act as an obstacle for
      nerve fiber regeneration on using LCNF as an interpositional nerve graft.

PMID- 20821406
TI  - Direct measurement of tibial cortical bone surface area.
AB  - Cortical bone surface area estimation is generally performed by analysis of
      medical images but its accuracy has not yet been verified by direct bone
      measurements. This study was performed to evaluate the reproducibility of direct
      ex vivo estimations of cross sectional tibial cortical bone surface area. Ten
      tibiae were evaluated by two observers using direct 3D-digitization at 38 and 66%
      of total tibial length using a 'critical' and a 'general' criterion for
      differentiation between cortical and cancellous bone. The results of the analysis
      using the more severe 'critical' differentiation criterion yielded high intra and
      interobserver agreement. Mean intraobserver reliability was demonstrated by R =
      0.98 (Spearman rank correlation between 0.98 and 0.97; P < 0.01) and inter
      observer reliability by R = 0.91 (Spearman rank correlation between 0.95 and
      0.88; P < 0.01). When using strict criteria to differentiate between cortical and
      cancellous bone, intra and interobserver reliability of the presented method of
      direct cortical bone surface area estimation is very high. The results indicate
      that cross-sectional cortical bone surface estimation by direct 3D-digitization
      can serve as a gold standard for validation of other estimations methods.

PMID- 20821405
TI  - Topographical anatomy of Spiegel's lobe and its adjacent organs in mid-term
      fetuses: Its implication on the development of the lesser sac and adult
      morphology of the upper abdomen.
AB  - At 8-16 weeks of gestation, Spiegel's lobe of the caudate lobe appears as a sac
      like herniation of the liver parenchyma between the inferior vena cava and ductus
      venosus or Arantius' duct. In 5 of 11 fetuses at 20-30 weeks of gestation, we
      found that an external notch was formed into the posterior aspect of the caudate
      lobe by a peritoneal fold containing the left gastric artery. This notch appeared
      to correspond to that observed in adults, which is usually seen at the antero
      inferior margin of the lobe after rotation of the lobe along the horizontal or
      transverse axis. However, the notch did not accompany two of the three fetuses in
      which the left hepatic artery originated from the left gastric artery. Notably,
      until 9-10 weeks of gestation, the inferior and left part of Spiegel's lobe rode
      over the hepatoduodenal ligament and protruded medially into the lesser sac
      (bursa omentalis) behind the stomach. Thus, the fetal Winslow's foramen was
      located at the "superior" side of the ligament. However, as seen in adults, the
      protruding Spiegel's lobe was located at the posterior side of the lesser
      omentum. Therefore, a hypothetical rotation along the transverse axis in the
      later stages of development seems necessary to explain this repositioning.
      Considering that Spiegel's lobe develops faster than surrounding structures, it
      is likely that the lesser sac resulting from the rotation of the gastrointestinal
      tract, which actively contributes to facilitate the growth of the Spiegel lobe.

PMID- 20821407
TI  - First-principles calculation of parameters of electron paramagnetic resonance
      spectroscopy in solids.
AB  - The hyperfine A-tensor and Zeeman g-tensor parameterize the interaction of an
      'effective' electron spin with the magnetic field due to the nuclear spin and the
      homogeneous external magnetic field, respectively. The A- and g-tensors are the
      quantities of primary interest in electron paramagnetic resonance (EPR)
      spectroscopy. In this paper, we review our work [E.S. Kadantsev, T. Ziegler, J.
      Phys. Chem. A 2008, 112, 4521; E. S. Kadantsev, T. Ziegler, J. Phys. Chem. A
      2009, 113, 1327] on the calculation of these EPR parameters under periodic
      boundary conditions (PBC) from first-principles. Our methodology is based on the
      Kohn-Sham DFT (KS DFT), explicit usage of Bloch basis set made up of numerical
      and Slater-type atomic orbitals (NAOs/STOs), and is implemented in the 'full
      potential' program BAND. Our implementation does not rely on the frozen core
      approximation. The NAOs/STOs basis is well suited for the accurate representation
      of the electron density near the nuclei, a prerequisite for the calculation of
      highly accurate hyperfine parameters. In the case of g-tensor, our implementation
      is based on the method of Van Lenthe et al. [E. van Lenthe, P. E. S. Wormer, A.
      van der Avoird, J. Chem. Phys. 1997, 107, 2488] in which the spin-orbital
      coupling is taken into account variationally. We demonstrate the viability of our
      scheme by calculating EPR parameters of paramagnetic defects in solids. We
      consider the A-tensor of 'normal' and 'anomalous' muonium defect in IIIA-VA
      semiconductors as well as the S2 anion radical in KCl host crystal lattice.

PMID- 20821408
TI  - Multi-regional clinical trials--what are the challenges?

PMID- 20821410
TI  - Long-TE 1H MRS suggests that liver fat is more saturated than subcutaneous and
      visceral fat.
AB  - Cross-talk between adipose tissue and liver is disturbed in the metabolic
      syndrome. Moreover, the relative fatty acid composition of adipose and liver fat
      is poorly characterized. Long-TE (1)H MRS can determine the unsaturation and
      polyunsaturation of adipose tissue. The aim of this study was to use long-TE (1)H
      MRS to determine the composition of liver fat and its relation to adipose tissue
      composition. Sixteen subjects with increased liver fat (>5%) were recruited for
      the study. Using TE = 200  ms, we were able to resolve the olefinic (=CH, 5.3 
      ppm) and water (H(2)O, 4.7  ppm) resonances in liver spectra and to obtain a
      repeatable estimate of liver fat unsaturation (coefficient of variation, 2.3%).
      With TE = 135  ms, the diallylic (=C-CH(2)-C=, 2.8  ppm) resonance was detectable
      in subjects with a liver fat content above 15%. Long-TE (1)H MRS was also used to
      determine the unsaturation in subcutaneous (n = 16) and visceral (n = 11) adipose
      tissue in the same subjects. Liver fat was more saturated (double bonds per fatty
      acid chain, 0.812 +/- 0.022) than subcutaneous (double bonds per fatty acid
      chain, 0.862 +/- 0.022, p < 0.0004) or visceral (double bonds per fatty acid
      chain, 0.865 +/- 0.033, p < 0.0004) fat. Liver fat unsaturation correlated with
      subcutaneous unsaturation (R = 0.837, p < 0.0001) and visceral unsaturation (R =
      0.879, p < 0.0004). The present study introduces a new noninvasive method for the
      assessment of the composition of liver fat. The results suggest that liver fat is
      more saturated than subcutaneous or visceral adipose tissue, which may be
      attributed to differences in de novo lipogenesis.

PMID- 20821409
TI  - MRI of retinal and choroidal blood flow with laminar resolution.
AB  - The retina is nourished by two distinct circulations: the retinal vessels within
      the inner retina and the choroidal vessels behind the neural retina. The outer
      nuclear layer and the inner and outer segments of the photoreceptors in between
      are avascular. The aim of this study was to determine whether arterial spin
      labeling MRI could provide sufficient resolution to differentiate between
      quantitative retinal blood flow (rBF) and choroidal blood flow (chBF), and
      whether this technique is sufficiently sensitive to detect vascular-specific
      blood flow (BF) changes modulated by anesthetics. Arterial spin labeling MRI was
      performed at 42 * 42 * 400 um(3) in the mouse retina at 7 T, and was used to
      investigate the effects of isoflurane and ketamine/xylazine anesthesia on rBF and
      chBF. MRI yielded unambiguous differentiation of rBF, chBF and the avascular
      layer in between. Under isoflurane, chBF was 7.7 +/- 2.1 mL/g/min and rBF was 1.3
      +/- 0.44 mL/g/min (mean +/- SD, n = 7, p < 0.01). Under ketamine/xylazine
      anesthesia in the same animals, chBF was 4.3 +/- 1.9 mL/g/min and rBF was 0.88 +/
      0.22 mL/g/min (p < 0.01). Under ketamine/xylazine anesthesia, rBF was lower by
      29% (P < 0.01) and chBF by 42% (P < 0.01) relative to isoflurane. This study
      demonstrates, for the first time, the quantitative imaging of rBF and chBF in
      vivo, providing a new method to study basal values and alterations of rBF and
      chBF.

PMID- 20821411
TI  - Complete assignment of the 1H and 13C NMR spectra of antimicrobial 4-arylamino- 3
      nitrocoumarin derivatives.
AB  - Herein, we describe the synthesis and complete assignment of the (1)H and (13)C
      NMR chemical shifts of a series of antimicrobial 4-arylamino-3-nitrocoumarin
      derivatives based on a combination of (1)H and (13)C NMR, (1)H-(1)H-COSY, NOESY,
      HSQC and HMBC experiments. Conformational effects upon the chemical shifts of the
      coumarin moiety arising from the anisotropy of the aryl side group are briefly
      discussed. This study provides the first complete and fully assigned NMR data for
      this important group of antimicrobial compounds and bridges the gap existing in
      the literature with regard to NMR structural data for 4-arylamino-3
      nitrocoumarins.

PMID- 20821412
TI  - First-principles calculations of NMR parameters for phosphate materials.
AB  - In this short review, we discuss the ability to reproduce NMR parameters in the
      case of phosphates materials through electronic structure calculation within
      density functional theory linear response. Indeed, the gauge-including projector
      augmented wave is today largely used by the solid-state NMR community as a tool
      for structural determination and it has been applied to a large variety of
      materials. We emphasise on the crucial points that should be taken into account
      to perform such calculations. In particular, we discuss the influence of the
      electronic structure and of the geometry on the calculation of NMR parameters. To
      illustrate the review, we present experimental and theoretical comparison of
      (31)P, (1)H and (23)Na NMR data on a series of sodium phosphate systems.

PMID- 20821413
TI  - Nanomaterials and the environment: the views of the Royal Commission on
      Environmental Pollution (UK).

PMID- 20821414
TI  - Cholinesterase and glutathione-S-transferase activities in freshwater
      invertebrates as biomarkers to assess pesticide contamination.
AB  - Studies investigating the use of biomarkers in pesticide risk assessment have
      greatly increased in recent years; however, issues concerning the ecological
      meaning of enzymatic responses have proved controversial. Ideally a good
      biomarker response should be modulated by the environmental contaminants alone
      and demonstrate a predictable behavior towards certain types of toxins. As these
      premises are rarely observed, the present study aims to outline research that has
      contributed to an understanding of the behavior of two widely used biomarkers,
      cholinesterase and glutathione-S-transferase, describing environmental and biotic
      factors that affect their response in freshwater invertebrates. Studies were
      performed in the main classes of aquatic invertebrates with these biomarkers and
      conclusions were reached concerning their behavior towards the main classes of
      pesticides. Links between biomarker responses and conventional endpoints were
      evaluated so that ecological relevance could be attributed to enzymatic
      responses. Toxicity of mixtures was investigated, and cases of synergism and
      antagonism were pointed out as factors changing the expected toxicity of aquatic
      systems and leading to misinterpretations of biomarker responses. Finally, the
      use of biomarkers as a tool for biomonitoring and in situ assays was
      investigated, with discussion of advantages and disadvantages of their use.

PMID- 20821415
TI  - Reconcilable differences: the use of reference material to reduce methodological
      artifacts in the reporting of organochlorine pesticides and polychlorinated
      biphenyls.
AB  - Numerous long-term monitoring programs have assessed spatial and temporal trends
      of organochlorine (OC) pesticides and polychlorinated biphenyls (PCBs). Changes
      in analytical approaches (e.g., gas chromatography coupled with electron capture
      detection [GC-ECD] versus mass spectrometric detection [GC-MSD]) can reveal
      artifacts in the reported concentrations. In-house reference material (RM) was
      used to determine the analytical artifacts in the measurement of OCs and PCBs in
      Great Lake herring gull eggs previously analyzed from 1994 to 1996 (GC-ECD) and
      1997 to 1999 (GC-MSD). Approximately 19.0% of the variability of PCB congeners in
      gull eggs was associated with analytical artifacts, and differences among
      colonies were obscured. Although the discrepancy in sum PCBs (SigmaPCBs) was
      fairly small (2.1%), some congeners varied considerably between methods (> 60%).
      After statistically removing the artifacts, only 1.4% of the variability in PCBs
      of herring gull eggs was associated with artifacts, and differences among gull
      colonies became apparent. After excluding OCs near the detection limit in the RM,
      statistically removing the artifacts reduced some of the differences between
      methods for OCs. Analytical artifacts may potentially render inferences
      difficult, confounded, and erroneous. When combining contaminant data obtained
      using different methods, the methods should be assumed to give different results
      unless demonstrated otherwise. Assessments of the compatibility of analytical
      methodologies should be made using an appropriate RM.

PMID- 20821416
TI  - Extent of copper tolerance and consequences for functional stability of the
      ammonia-oxidizing community in long-term copper-contaminated soils.
AB  - Adaptation of soil microbial communities to elevated copper (Cu) concentrations
      has been well documented. However, effects of long-term Cu exposure on adaptation
      responses associated with functional stability and structural composition within
      the nitrifying community are still unknown. Soils were sampled in three field
      sites (Denmark, Thailand, and Australia) where Cu gradients had been established
      from 3 to 80 years prior to sampling. In each field site, the potential
      nitrification rate (PNR) decreased by over 50% with increasing soil Cu,
      irrespective of a 20 to >200-fold increase in Cu tolerance (at the highest soil
      Cu) among the nitrifying communities. This increased tolerance was associated
      with decreasing numbers (15-120-fold) of ammonia-oxidizing bacteria (AOB), except
      in the oldest contaminated field site, decreasing numbers of ammonia-oxidizing
      archaea (AOA; 10-130-fold) and differences in the operational taxonomic unit
      (OTU) composition of the AOB and, to a lesser extent, AOA communities. The
      sensitivity of nitrifying communities, previously under long-term Cu exposure, to
      additional stresses was assessed. Nitrification in soils from the three field
      sites was measured following acidification, pesticide addition, freeze-thaw
      cycles, and dry-rewetting cycles. Functional stability of the nitrification
      process was assessed immediately after stress application (resistance) and after
      an additional three weeks of incubation (resilience). No indications were found
      that long-term Cu exposure affected the sensitivity to the selected stressors,
      suggesting that resistance and resilience were unaffected. It was concluded that
      the nitrifying community changed structurally in all long-term Cu-exposed field
      sites and that these changes were associated with increased Cu tolerance but not
      with a loss of functional stability.

PMID- 20821417
TI  - Bacterial community dynamics in high and low bioavailability soils following
      laboratory exposure to a range of hexahydro-1,3,5-trinitro-1,3,5-triazine
      concentrations.
AB  - Few studies have examined the potential long-term effects of high concentrations
      of hexahydro-1,3,5-trinitro-1,3,5-triaxine (RDX) on bacterial communities in
      soil. In the present study, a sandy loam soil and a silt loam soil (high and low
      bioavailability, respectively) were artificially contaminated with RDX (0, 50,
      500, 1,500, 5,000, 10,000, and 15,000 mg/kg soil). Bacterial communities from
      each treatment were monitored over 63 d to characterize the effects of RDX
      exposure on bacterial activity, biomass, functional diversity (Biolog microtiter
      plates), and structural diversity (denaturing gradient gel electrophoresis of 16S
      rDNA). Bacterial communities native to the high bioavailability soil were
      inherently different than bacterial communities native to the silt loam soil, not
      only in terms of bacterial activity and biomass, but also in terms of bacterial
      community functional and structural diversity. Soil RDX contamination was
      correlated with decreased bacterial biomass in the silt loam soil treatments and
      with decreased bacterial activity in the sandy loam soil treatments on day 7.
      Soil RDX contamination did not cause a significant shift in the functional
      diversity of the bacterial communities native to the silt loam soil, but was
      correlated with a shift in identities of substrates used by bacterial communities
      native to the sandy loam soil on day 7. Bacterial community structure was
      insensitive to the gradient of RDX concentrations at the beginning of the
      incubation. However, the identities of carbon substrates used by bacterial
      communities in both soil types were affected by long-term incubation with RDX.

PMID- 20821418
TI  - Multimedia modeling of human exposure to chemical substances: the roles of food
      web biomagnification and biotransformation.
AB  - The Risk Assessment IDentification And Ranking (RAIDAR) model is refined to
      calculate relative human exposures as expressed by total intake, intake fraction
      (iF), and total body burden (TBB) metrics. The RAIDAR model is applied to three
      persistent organic pollutants (POPs) and six petrochemicals using four mode-of
      entry emission scenarios to evaluate the effect of metabolic biotransformation
      estimates on human exposure calculations. When biotransformation rates are
      assumed to be negligible, daily intake and iFs for the nine substances ranged
      over six orders of magnitude and TBBs ranged over 10 orders of magnitude.
      Including biotransformation estimates for fish, birds, and mammals reduced
      substance-specific daily intake and iF by up to 4.5 orders of magnitude and TBB
      by more than eight orders of magnitude. The RAIDAR iF calculations are compared
      to the European Union System for the Evaluation of Substances (EUSES) model iF
      calculations and differences are discussed, especially the treatment of food web
      bioaccumulation. Model selection and application assumptions result in different
      rankings of human exposure potential. These results suggest a need to critically
      consider model selection and to include reliable biotransformation rate estimates
      when assessing relative human exposure and ranking substances for priority
      setting. Recommendations for further model evaluations and revisions are
      discussed.

PMID- 20821419
TI  - Kinetics of trichloroethylene and toluene toxicity to Pseudomonas putida F1.
AB  - The goal of the present study was to elucidate the distribution of viable
      bacteria in chemical gradients and to evaluate the toxic effect of high
      concentrations of contaminants on contaminant-degrading bacteria under prolonged
      exposure. Accumulations of viable Pseudomonas putida F1 (P. putida F1) cells were
      observed surrounding trichloroethylene (TCE)-containing plugs. Results from this
      work indicate that P. putida F1 immediately adjacent to a TCE source become
      nonviable, whereas cells accumulating farther away use chemotaxis to migrate
      toward regions with optimal chemical concentrations in the form of concentrated
      bacterial bands. A method was developed to test the toxicity of model contaminant
      stressors, TCE and toluene, to P. putida F1; data obtained from toxicity
      experiments were fit to linear and exponential bacterial viability-decay models.
      Toxicity of TCE to P. putida F1 was best described with an exponential viability
      decay model, with a viability-decay constant k(TCE) = 0.025 h(-4.95) (r(2) =
      0.965). Toluene toxicity showed a marginally better fit to the linear viability
      decay model (r(2) = 0.976), with a viability-decay constant k(toluene) = 0.208 h(
      1). Best-fit model parameters obtained for both TCE and toluene were used to
      predict bacterial viability in toxicity experiments with higher contaminant
      concentrations and matched well with experimental data. Results from the present
      study can be used to predict bacterial accumulation and viability near nonaqueous
      phase liquid (NAPL) sources in groundwater and may be helpful in designing
      bioremediation strategies for sites contaminated with residual NAPLs.

PMID- 20821420
TI  - Hierarchical cluster analysis of polychlorinated dioxins and furans in Michigan,
      USA, soils: evaluation of industrial and background congener profiles.
AB  - As part of the University of Michigan Dioxin Exposure Study, soil samples were
      collected from 766 residential properties near the Tittabawassee River between
      Midland and Saginaw; near the Dow Chemical Facility in Midland; and, for
      comparison, in the other areas of Midland and Saginaw Counties and in Jackson and
      Calhoun Counties, all located in the state of Michigan, USA. A total of 2,081
      soil samples were analyzed for 17 polychlorinated dibenzo-p-dioxins (PCDDs) and
      polychlorinated dibenzofurans (PCDFs). In order to better understand the
      distribution and sources of the PCDD/F congeners in the study area, hierarchical
      cluster analysis (HCA) was used to statistically group samples with similar
      congener patterns. The analysis yielded a total of 13 clusters, including: 3
      clusters among the soils impacted by contamination present in the Tittabawassee
      River sediments, a cluster comprised mainly of samples collected within the
      depositional area of the Dow incinerator complex, a small cluster of samples with
      elevated 2,3,7,8-tetrachlorinated dibenzo-p-dioxin (TCDD), and several clusters
      exhibiting background patterns. The clusters related to the Tittabawassee River
      floodplain contamination all contained elevated PCDF levels and were
      differentiated from one another primarily by their relative concentrations of
      higher-chlorinated PCDDs, a difference likely related to both extent and timing
      of impacts from Tittabawassee sediments. The background clusters appear to be
      related to combustion processes and are differentiated, in part, by their
      relative fractions of TCDD. Thus, HCA was useful for identifying congener profile
      characteristics in both contaminated and background soil samples.

PMID- 20821421
TI  - Quantifying the antiestrogen activity of wastewater treatment plant effluent
      using the yeast estrogen screen.
AB  - The yeast estrogen screen (YES) assay was used to measure both estrogenic and
      antiestrogenic activity of wastewater treatment plant (WWTP) effluent for the
      purpose of developing a method to quantify antiestrogenic activity. Wastewater
      treatment plant effluent samples were concentrated by solid-phase extraction
      (SPE) and serially diluted. Five microliters of each dilution plus 195 microl of
      assay medium was placed in well plates and tested for estrogenic substances.
      Antiestrogen activity in WWTP effluent samples was indirectly measured by an
      effluent-volume-dependent suppression of the beta-galactosidase activity induced
      by an estradiol (E2) standard. Antiestrogens and estrogens were quantified by
      median inhibition concentration (IC50) and median effective concentration (EC50)
      statistics, respectively, and were expressed in terms of effluent volume (prior
      to concentration by SPE). Antiestrogen IC50 and estrogen EC50 values, calculated
      by standard linear regression methods, averaged 25.6 microl and 22.1 microl
      effluent, respectively. Taken together, these values suggest that antiestrogens
      were responsible for approximately a 50% reduction in estrogen-induced activity
      in WWTP effluent. Therefore, measurements of estrogenicity by the YES assay in
      WWTP effluent that typically contains a mixture of estrogenic and antiestrogenic
      substances should be considered net estrogenic activity. The potential for false
      positive antiestrogen activity was addressed by assays of beta-galactosidase
      activity in effluent, by measurements of yeast cell turbidity, and by stirred
      cell ultrafiltration for removal of solid-phase coextracted organic substances.

PMID- 20821422
TI  - Antidepressants and their metabolites in municipal wastewater, and downstream
      exposure in an urban watershed.
AB  - Antidepressants are a widely prescribed group of pharmaceuticals that can be
      biotransformed in humans to biologically active metabolites. In the present
      study, the distribution of six antidepressants (venlafaxine, bupropion,
      fluoxetine, sertraline, citalopram, and paroxetine) and five of their metabolites
      was determined in a municipal wastewater treatment plant (WWTP) and at sites
      downstream of two WWTPs in the Grand River watershed in southern Ontario, Canada.
      Fathead minnows (Pimephales promelas) caged in the Grand River downstream of a
      WWTP were also evaluated for accumulated antidepressants. Finally, drinking water
      was analyzed from a treatment plant that takes its water from the Grand River 17
      km downstream of a WWTP. In municipal wastewater, the antidepressant compounds
      present in the highest concentrations (i.e., >0.5 microg/L) were venlafaxine and
      its two demethylation products, O- and N-desmethyl venlafaxine. Removal rates of
      the target analytes in a WWTP were approximately 40%. These compounds persisted
      in river water samples collected at sites up to several kilometers downstream of
      discharges from WWTPs. Venlafaxine, citalopram, and sertraline, and demethylated
      metabolites were detected in fathead minnows caged 10 m below the discharge from
      a WWTP, but concentrations were all < microg/kg wet weight. Venlafaxine and
      bupropion were detected at very low (<0.005 microg/L) concentrations in untreated
      drinking water, but these compounds were not detected in treated drinking water.
      The present study illustrates that data are needed on the distribution in the
      aquatic environment of both the parent compound and the biologically active
      metabolites of pharmaceuticals.

PMID- 20821423
TI  - Binding of ciprofloxacin by humic substances: a molecular dynamics study.
AB  - A comprehensive assessment of the potential impacts of antimicrobials released
      into the environment requires an understanding of their sequestration by natural
      particles. Of particular interest are the strong interactions of antimicrobials
      with natural organic matter (NOM), which are believed to reduce their
      bioavailability, retard their abiotic and biotic degradation, and facilitate
      their persistence in soils and aquatic sediments. Molecular dynamics (MD)
      relaxation studies of a widely used fluoroquinolone antibiotic, ciprofloxacin
      (Cipro), interacting with a model humic substance (HS) in a hydrated environment,
      were performed to elucidate the mechanisms of these interactions. Specifically, a
      zwitterionic Cipro molecule, the predominant species at circumneutral pH, was
      reacted either with protonated HS or deprotonated HS bearing Ca, Mg, or Fe(II)
      cations. The HS underwent conformational changes through rearrangements of its
      hydrophobic and hydrophilic regions and disruption of its intramolecular H-bonds
      to facilitate favorable intermolecular H-bonding interactions with Cipro.
      Complexation of the metal cations with HS carboxylates appeared to impede binding
      of the positively charged amino group of Cipro with these negatively charged HS
      complexation sites. On the other hand, an outer-sphere complex between Cipro and
      the HS-bound cation led to ternary Cipro-metal-HS complexes in the case of Mg-HS
      and Fe(II)-HS, but no such bridging interaction occurred with Ca-HS. The results
      suggested that the ionic potential (valence/ionic radius) of the divalent cation
      may be a determining factor in the formation of the ternary complex, with high
      ionic potential favoring the bridging interaction. Environ. Toxicol. Chem.
      2010;29:90-98. (c) 2009 SETAC.

PMID- 20821424
TI  - Polychlorinated biphenyls, dioxins, furans, and organochlorine pesticides in
      belted kingfisher eggs from the upper Hudson River basin, New York, USA.
AB  - Nesting belted kingfishers (hereafter kingfishers, Ceryle alcyon) were studied on
      the Hudson River near Fort Edward south to New Baltimore (NY, USA) and three
      nearby river drainages in 2004. Concentrations of 28 organochlorine pesticides,
      160 polychlorinated biphenyl (PCB) congeners, and 17 dioxin and furan (PCDD-F)
      congeners were quantified in kingfisher eggs. The pattern of organochlorine
      pesticides and PCDD-F congeners did not differ significantly between 14 eggs
      collected from individual nests on the Hudson River and five eggs similarly
      collected on three other nearby rivers. In contrast, the pattern of PCB congeners
      in eggs collected on the Hudson River differed significantly from the other
      rivers. The differences in patterns of PCB congeners were associated with a
      higher representation of lower-numbered congeners on the Hudson River than the
      other rivers. The higher prevalence of the lower-numbered congeners and lower
      prevalence of the higher-numbered congeners is consistent with Aroclor 1016 and
      1242 being the source of the PCBs on the Hudson River. Concentrations in a sample
      egg collected at each nest were compared to nest survival and egg success (the
      proportion of eggs hatching in a clutch if at least one egg hatched) of the
      remaining eggs in the clutch. Models that predicted nest survival and egg success
      as functions of contaminant levels were poorly distinguished from models that
      presumed no such associations. Small sample sizes could have contributed to the
      inability to distinguish among contaminant and no toxicant models. However, we
      cannot rule out the possibility that contaminant concentrations on the Hudson
      River were not sufficiently high to demonstrate a relationship between
      contaminant concentrations and reproductive success in kingfishers.

PMID- 20821425
TI  - Potato (Solanum tuberosum) greenhouse tuber production as an assay for asexual
      reproduction effects from herbicides.
AB  - The present study determined whether young potato plants can be used as an assay
      to indicate potential effects of pesticides on asexual reproduction. Solanum
      tuberosum (Russet Burbank) plants were grown from seed pieces in a mineral soil
      in pots under greenhouse conditions. Plants were treated with herbicides
      (cloransulam, dicamba, glyphosate, imazapyr, primsulfuron, sulfometuron, or
      tribenuron) at simulated drift levels [</=0.1 x standard field application rates
      (f.a.r.)], approximately 14 d after emergence (DAE). Plant height was measured
      approximately 14 d after treatment (DAT). Production of small tubers and shoot
      dry weight were determined at approximately 28 DAT. Imazapyr, sulfometuron, and
      tribenuron caused significant reductions in tuber fresh weight, with the
      effective concentrations producing a 25% potato tuber fresh weight (EC25) of
      0.00038, 0.0016, and 0.0021 x f.a.r. of 1,124, 52, and 9 g active ingredient
      hectare(-1) (g a.i. HA(-1)), respectively. Primisulfuron, dicamba, and
      cloransulam also significantly reduced tuber fresh weight, but with higher EC25
      values of 0.011, 0.07, and 0.010 to 0.2 x f.a.r. of 40, 558, and 18 g a.i. HA(
      1), respectively. Glyphosate had little effect on tuber fresh weight, with a
      significant reduction in only one experiment. Sulfometuron reduced tuber fresh
      weight at an EC25 value lower than the EC25 values for shoot dry weight or plant
      height. For other herbicides, the reduction in tuber fresh weight occurred within
      the range of EC25 values for other responses. Although additional experiments are
      required to develop further a phytotoxicity test, these results indicated that
      tuber production in young potato plants (harvested approximately 42 DAE) may be
      an effective assay for below-ground asexual reproductive responses to herbicides,
      especially acetolactate synthase inhibitors.

PMID- 20821426
TI  - Acute toxicity of a mixture of copper and single-walled carbon nanotubes to
      Daphnia magna.
AB  - Nanomaterials released into the environment will interact with many materials
      including other contaminants. This may influence bioavailability and fate of both
      the nanoparticles and the other contaminants. The present study examined the
      effect of a combination of soluble copper and surface-modified single-walled
      carbon nanotubes (SWNTs) on Daphnia magna. Lysophosphatidylcholine (LPC) was used
      to modify the surface of SWNTs, reducing the surface hydrophobicity of the tubes
      and thereby producing a stable aqueous nanoparticle suspension. The toxicity of
      the nanoparticle-copper (Cu) mixture was determined to be additive. The addition
      of nontoxic concentration of LPC-SWNTs enhanced the uptake and toxicity of
      copper. Greater amounts of Cu were shown to accumulate in D. magna upon addition
      of 0.5 and 1.0 mg/L LPC-SWNTs.

PMID- 20821427
TI  - Toxicities of fipronil enantiomers to the honeybee Apis mellifera L. and
      enantiomeric compositions of fipronil in honey plant flowers.
AB  - Fipronil is a chiral phenylpyrazole insecticide that is effective for control of
      a wide range of agricultural and domestic pests at low application rates. Wide
      application of fipronil also causes poisoning of some nontarget insects, such as
      honeybees. In the present study, toxicities of fipronil enantiomers and racemate
      to the honeybee Apis mellifera L. were determined to examine whether using
      formulations of single or enriched fipronil enantiomer is a possible option to
      reduce risks to bees. Contact toxicity tests yielded median lethal doses (LD50)
      of 3.45, 3.38, and 3.86 ng/bee for the R(-)-enantiomer, S(+)-enantiomer, and
      racemate, respectively. Analysis of variance indicates that the LD50 values are
      not statistically different (p = 0.41). Oral toxicities of the R-enantiomer, S
      enantiomer, and racemate (nominal median lethal concentration = 0.037, 0.045,
      0.053 mg/L, respectively) were also demonstrated to be not statistically
      different (p = 0.20). In addition, enantiomeric fractions of fipronil in the
      flowers of three honey plants (Brassica campestris, Cucumis sativus, and
      Chrysanthemum indicum L.) were examined after treatment with fipronil. It was
      found that degradation of fipronil in all three plants is not enantioselective.
      These results indicate that it is unlikely that use of formulations with single
      or enriched fipronil enantiomer would reduce the risk that fipronil poses to
      honeybees. Improved fipronil application practices (based on safest timing and
      bloom conditions) and reduction of overall fipronil usage seem to be more
      realistic options.

PMID- 20821428
TI  - Chronic, dietary polybrominated diphenyl ether exposure affects survival, growth,
      and development of Rana pipiens tadpoles.
AB  - Levels of polybrominated diphenyl ethers (PBDEs) in the environment have been
      increasing rapidly over the past two decades; however, the toxicology of these
      compounds to aquatic organisms is poorly understood. Because amphibians play a
      role in both aquatic and terrestrial food webs, and are currently undergoing
      worldwide population declines, it is of interest to determine how PBDEs may
      affect amphibian health. This is the first study that reports chronic, dietary
      effects of environmentally relevant levels (7-277 ng/g wet food) of PBDEs in
      amphibians throughout larval development. Beginning at the free-swimming stage
      (Gosner Stage [GS] 25), Rana pipiens tadpoles were orally exposed to a technical
      pentabromodiphenyl ether mixture (DE-71) through metamorphic climax (GS 42). On
      exposure day 43, a subset of tadpoles was removed for body residue analysis. Sum
      PBDEs in whole-body tissue correlated linearly to dietary concentrations with BDE
      99 represented as the highest contributing congener in both diet and tissue.
      Survival among all treatments compared to the control was decreased by DE-71
      exposure. Further, growth and development were delayed in all but the highest
      treatment, perhaps indicating greater PBDE tolerance among those individuals that
      survived the highest treatment. Time to metamorphic climax was delayed, on
      average, 22 to 36 d in DE-71-treated tadpoles compared to control tadpoles.
      Additionally, size at metamorphosis was smaller in the highest treatment,
      suggesting that individuals that survived and metamorphosed similarly to the
      controls did so with a trade-off in size. At environmentally relevant levels,
      PBDEs induced mortality as well as sublethal effects on developing tadpoles
      through dietary exposure.

PMID- 20821429
TI  - Dieldrin uptake and translocation in plants growing in hydroponic medium.
AB  - It has been known that the Cucurbitaceae family takes up a large amount of
      persistent organic pollutants from soils and that the translocation of those
      compounds in cucurbits is higher than those in non-cucurbits. To understand the
      persistent organic pollutant uptake mechanisms of plant species, we compared the
      dieldrin absorption and transportation potentials of several plants in hydroponic
      medium. Sorghum (Sorghum vulgare Moench), sunflower (Helianthus annuus L.),
      soybean (Glycine max), komatsuna (Brassica rapa var. peruviridis), white-flowered
      gourd (Lagenaria siceraria var. hispida), cucumber (Cucumis sativus L.), and
      zucchini (Cucurbita pepo L.) were grown in a dieldrin-added hydroponic medium for
      10 d, and then the amount of dieldrin in their shoots and roots was measured. All
      of the roots contained dieldrin, whereas only the cucurbits (white-flowered
      gourd, cucumber, and zucchini) contained considerable amounts of dieldrin in
      their shoots. The dieldrin uptake to the roots depended on the concentration of
      the n-hexane soluble components in the roots, regardless of whether the dieldrin
      in the roots was translocated to shoots or not. The dieldrin uptake from the
      solution to the roots was thought to be due to a passive response, such as
      adsorption on the roots. The translocation of dieldrin from the roots to the
      shoots was probably through the xylems. The amounts of dieldrin in the shoots per
      transpiration rates were higher for cucurbits than for non-cucurbits. It seems
      likely that cucurbits have uptake mechanisms for hydrophobic organic chemicals.

PMID- 20821430
TI  - Distribution and toxicity of sediment-associated pesticides in urban and
      agricultural waterways from Illinois, USA.
AB  - A statewide investigation of insecticide presence and sediment toxicity was
      conducted in Illinois, USA, from June to August 2008. Twenty sediment samples
      were collected from urban areas throughout Illinois, and 49 sediment samples were
      collected from 14 agriculture-dominated counties in central and southern
      Illinois. Ten-day sediment toxicity tests were conducted using the amphipod
      Hyalella azteca, and 59% of the urban sites and 2% of the agricultural locations
      sampled caused significant mortality in the amphipods. The field sediments were
      analyzed for 29 pesticides, including 19 organochlorines, one organophosphate,
      and nine pyrethroids. The detection frequencies of organochlorines, chlorpyrifos,
      and pyrethroids were 95, 65, and 95%, respectively, for urban sites, and 45, 6.1,
      and 47%, respectively, for agricultural sites. Based on toxic unit analysis,
      bifenthrin was the main contributor to the detected mortality in urban sediments.
      The present study provides the first broad assessment of pesticide prevalence in
      both urban and agriculture areas in Illinois.

PMID- 20821431
TI  - Identifying the causes of sediment-associated contamination in the Illinois River
      (USA) using a whole-sediment toxicity identification evaluation.
AB  - Whole-sediment toxicity identification evaluation (TIE) techniques were employed
      on the Illinois River Complex (IRC), USA to identify the sources of sediment
      toxicity that may have contributed to the decline in benthic invertebrate
      populations. The TIE focused on three classes of contaminants: ammonia, metals,
      and organics. Sediment toxicity was assessed using the amphipod Hyalella azteca,
      and the focus of the TIE was on assessing spatial and temporal patterns of
      contamination. Past studies suggested that ammonia was the major source of
      contamination in IRC sediments. However, the present study suggested that
      polycyclic aromatic hydrocarbons (PAHs) were the primary contributor to sediment
      toxicity. Phase I testing showed 46% of the site trials (12 of 26) exhibited
      increased H. azteca survival (p < 0.05) with the addition of powdered coconut
      charcoal (organic amendment), whereas zeolite (ammonia amendment) and Resin Tech
      SIR 300 (cationic metals amendment) did not increase H. azteca survival. Phase II
      testing revealed PAH concentrations were high enough to cause the observed
      toxicity, confirming phase I results. Spatially, sediment toxicity as well as
      pore-water ammonia concentrations declined with distance downstream from
      suspected contaminant sources, indicating a potential dilution or remedial
      effect. Temporally, pore-water ammonia, metals, and PAH concentrations varied
      among sampling periods over an annual cycle for some sites near urbanized areas,
      while remaining temporally consistent at others. The results of the present study
      provide new information on the sources of toxicity within the IRC, and
      demonstrate the importance of evaluating spatial and temporal aspects in sediment
      TIEs. This is particularly important for evaluations in riverine systems in which
      hydrologic processes can result in large variation in sediment toxicity on
      temporal and spatial scales.

PMID- 20821432
TI  - The effects of continuous and pulsed exposures of suspended clay on the survival,
      growth, and reproduction of Daphnia magna.
AB  - Suspended sediments are a natural component of aquatic ecosystems, but
      anthropogenic activity such as land development can result in significant
      increases, especially after rain events. Continuous exposures of suspended clay
      and silt have been shown to affect growth and reproduction of Cladocera, leading
      to a decrease in population growth rate. The mechanism of clay toxicity in these
      filter-feeding organisms is clogging of the gut tract, resulting in decreased
      food uptake and assimilation. When placed in clean water, daphnids can purge clay
      from their gut and recover. In many surface waters, aquatic organisms experience
      episodic exposures of high concentrations of suspended solids driven by rain
      events. However, little is known about the consequences of pulsed exposures on
      individuals and populations. The objective of the present study was to
      characterize the effects of continuous and pulsed exposures of natural and
      defined clays on survival, growth, and reproduction of Daphnia magna. Two defined
      clays, montmorillonite and kaolinite, as well as clay isolated from the Piedmont
      region of South Carolina, USA, were used. Continuous exposures of clays elicited
      a dose dependent decrease in survival. Toxicity varied depending on clay source
      with montmorillonite > natural clay > kaolinite. Pulsed exposures caused a
      decrease in survival in a 24 h exposure of 734 mg/L kaolinite. Exposure to 73.9
      mg/L also caused an increase in the time to gravidity, although there was not a
      corresponding decrease in neonate production over 21 d. No significant effects
      resulted from 12 h exposures even at 730 mg/L, almost 10 times the 24-h
      reproductive effects concentration. This suggests that exposure duration impacted
      toxicity more than exposure concentration in these pulsed exposures.

PMID- 20821433
TI  - Perinatal exposure to bisphenol-A changes N-methyl-D-aspartate receptor
      expression in the hippocampus of male rat offspring.
AB  - Bisphenol-A (BPA) is one of the most common environmental endocrine disrupters
      with mixed estrogen agonist/antagonist properties. The toxicity of BPA has been
      extensively evaluated in a variety of tests in rodents, including developmental
      and reproductive toxicity, and carcinogenicity. The objective of the present
      study is to evaluate whether or not perinatal maternal exposure to BPA at 0.05,
      0.5, 5, 50, and 200 mg/kg/d affects N-methyl-D-aspartate (NMDA) receptor (NMDAR)
      subunits NR1, NR2A, 2B, estrogen receptor beta (ERbeta), and aromatase cytochrome
      P450 (P450arom) protein expressions of hippocampus in male rat offspring during
      postnatal development. Western-blotting analyses showed that perinatal exposure
      to BPA significantly affected the expression of NMDAR subunits. At the lower
      doses of 0.05 to 50 mg/kg/d, BPA concentration dependently inhibited the
      expression of NMDAR subunits. However, at the higher dose (200 mg/kg/d), the
      effects of BPA on these subunits were different, with a stronger inhibition of
      NR1 expression and a slighter inhibition of NR2A, 2B expression when compared
      with those at the lower dosage of BPA. In addition, perinatal exposure to BPA
      inhibited the expression of ERbeta protein, but increased P450arom protein
      expression in a concentration-dependent manner, especially during the early
      postnatal period (the first 1-3 postnatal weeks). No significant influence of BPA
      on P450arom was observed at postnatal week 8. These data suggest that
      environmental BPA exposure may affect the development of the brain, enhancing the
      local biosynthesis of estrogen in the brain, inhibiting ERbeta and NMDAR
      expressions.

PMID- 20821434
TI  - Cry1Ab toxin production of MON 810 transgenic maize.
AB  - Levels of Cry1Ab toxin were detected in genetically modified maize of genetic
      event MON 810 against near isogenic maize as negative control by two commercial
      immunoassays. The immunoassays were characterized for their cross-reactivity (CR)
      between Cry1Ab protoxin and activated toxin, and were compared with each other
      for toxin detection in a reference plant sample. Cry1Ab toxin levels, corrected
      for active toxin content using the CR values obtained, were monitored in maize DK
      440 BTY through the entire vegetation period. The toxin concentration was found
      to show a rapid rise in the leaves to 17.15 +/- 1.66 microg/g by the end of the
      fifth week of cultivation, followed by a gradual decline to 9.61 +/- 2.07
      microg/g by the 16th week and a slight increase again to 13.51 +/- 1.96 microg/g
      during the last 2 weeks due to partial desiccation. Similar but lesser
      fluctuation of toxin levels was seen in the roots between 5.32 +/- 0.49 microg/g
      at the less differentiated V1 stage and 2.25 +/- 0.30 microg/g during plant
      development. In contrast, Cry1Ab toxin levels appeared to be stably 1.36 +/-
      0.45, 4.98 +/- 0.31, 0.47 +/- 0.03, and 0.83 +/- 0.15 microg/g in the stem,
      anther wall, pollen, and grain, respectively. Toxin concentrations produced at
      the VT-R4 phenological stages under actual cultivation conditions were compared
      with each other in three different years within an 8-year period.

PMID- 20821435
TI  - Differential effects of copper and cadmium exposure on toxicity endpoints and
      gene expression in Chlamydomonas reinhardtii.
AB  - The toxicity of cadmium to aquatic organisms is well known, but the mechanisms of
      toxicity are not as clearly understood. In the present study, Cd bioassay
      experiments incorporating both traditional endpoints and novel thiol-based
      endpoints were conducted with Chlamydomonas reinhardtii. The results were
      compared with results from previous bioassay experiments to probe the apparent
      contrasting biochemical mechanisms of toxicity of copper and cadmium as expressed
      in cellular glutathione and the glutathione cycle. Total glutathione and reduced
      to oxidized glutathione ratio (GSH/GSSG) measurements were remarkably different
      in Cd- compared with Cu-exposed cells. Whereas total glutathione in cells
      decreased with increasing Cu concentration, Cd caused dramatic increases. Total
      glutathione increased by 4.5-fold with 80 nM Cd treatment over concentrations in
      Cd-free controls. Glutathione reductase (GR) enzyme activity was positively
      correlated (r(2) (Cu) = 0.96, r(2) (Cd) = 0.85) with glutathione concentrations
      for both metals. Measurements of mRNA for GR were increased 2-fold in response to
      Cd exposure (80 nM) and correlated well with GR enzyme activity. Glutathione
      concentrations and GR enzyme activity are useful endpoints for both Cu and Cd
      toxicity in algae, even though the metals elicit opposing responses. We conclude
      that Cu decreases glutathione concentrations by inhibiting GR enzyme activity. In
      contrast, Cd stimulates GR enzyme activity and increases glutathione
      concentrations as cells respond to Cd-induced stress by producing increased
      antioxidant capacity. The present study demonstrates that determining the
      glutathione response in cells is important for understanding the metal-specific
      mechanisms of toxicity and that these associated novel endpoints may be useful
      metrics for accurately predicting toxicity.

PMID- 20821436
TI  - Toxicity of the herbicides bromacil and simazine to the aquatic macrophyte,
      Vallisneria americana Michx.
AB  - Vallisneria americana Michx. (tapegrass) is an ecologically important submersed,
      vascular aquatic plant that provides food and shelter for many aquatic and
      waterfowl species. This plant often occurs close to land areas where herbicides
      are used. Nontarget exposure of these plants to herbicides may compromise
      ecological structure and function. The objective of the present study was to
      evaluate the suitability of several endpoint measurements for determining no
      observable-adverse effect concentrations (NOAECs), lowest-observable-adverse
      effect concentrations (LOAECs), and median effective concentration values (EC50s)
      for tapegrass exposed to the herbicides bromacil (0-0.092 mg/L) and simazine (0
      0.592 mg/L) following a 13-d single-pulse exposure and 15-d (bromacil) or 14-d
      (simazine) postexposure periods. The NOAEC/LOAEC/EC50 for fresh weight gains, new
      leaf production, and total leaf growth after 13-d exposure to bromacil were
      0.020/0.036/0.032, 0.036/0.054/0.036, and 0.036/0.054/0.043 mg/L, respectively.
      The same respective NOAEC/LOAEC/EC50s for simazine were <0.058/0.058/0.067,
      0.229/0.344/0.154, and 0.058/0.116/0.081 mg/L. Reductions in quantity and fresh
      weight of daughter plants produced and stolon fresh weights occurred at bromacil
      concentrations > or = 77, 0.020, and 0.036 mg/L, respectively; and simazine
      concentrations > or = 0.344, >0.592, and > or = 0.116 mg/L, respectively. Neither
      herbicide affected leaf greenness, total chlorophyll concentrations, or
      carbohydrate allocation. Although toxicity was shown for many endpoints, most
      EC50 values were greater than aquatic life benchmark values for algae used by the
      U.S. Environmental Protection Agency (U.S. EPA), but less than for aquatic
      plants, indicating that V. americana would likely be protected by use of the
      algal benchmark criteria.

PMID- 20821437
TI  - Comparing methods for analyzing overdispersed count data in aquatic toxicology.
AB  - Endpoints in aquatic toxicity tests can be measured using a variety of
      measurement scales including dichotomous (survival), continuous (growth) and
      count (number of young). A distribution is assumed for an endpoint and analyses
      proceed accordingly. In certain situations, the assumed distribution may be
      incorrect and this may lead to incorrect statistical inference. The present study
      considers the analysis of count effects, here motivated by the Ceriodaphnia dubia
      reproduction study. While the Poisson probability model is a common starting
      point, this distribution assumes that the mean and variance are the same. This
      will not be the case if there is some extraneous source of variability in the
      system, and in this case, the variability may exceed the mean. A computer
      simulation study was used to examine the impact of overdispersion or outliers on
      the analysis of count data. Methods that assumed Poisson or negative binomially
      distributed outcomes were compared to methods that accommodated this potential
      overdispersion using quasi-likelihood (QL) or generalized linear mixed models
      (GLMM). If the data were truly Poisson, the adjusted methods still performed at
      nominal type I error rates. In the cases of overdispersed counts, the Poisson
      assumed methods resulted in rejection rates that exceeded nominal levels and
      standard errors for regression coefficients that were too narrow. The negative
      binomial methods worked best in the case when the data were, in fact, negative
      binomial but did not maintain nominal characteristics in other situations. In
      general, the QL and GLMM methods performed reasonably based on the present study,
      although all procedures suffered some impact in the presence of potential
      outliers. In particular, the QL is arguably preferred because it makes fewer
      assumptions than the GLMM and performed well over the range of conditions
      considered.

PMID- 20821438
TI  - Toward a unified approach to dose-response modeling in ecotoxicology.
AB  - This study reviews dose-response models that are used in ecotoxicology. The focus
      lies on clarification of differences and similarities between models, and as a
      side effect, their different guises in ecotoxicology are unravelled. A look at
      frequently used dose-response models reveals major discrepancies, among other
      things in naming conventions. Therefore, there is a need for a unified view on
      dose-response modeling in order to improve the understanding of it and to
      facilitate communication and comparison of findings across studies, thus
      realizing its full potential. This study attempts to establish a general
      framework that encompasses most dose-response models that are of interest to
      ecotoxicologists in practice. The framework includes commonly used models such as
      the log-logistic and Weibull models, but also features entire suites of models as
      found in various guidance documents. An outline on how the proposed framework can
      be implemented in statistical software systems is also provided.

PMID- 20821439
TI  - Direct application of biota-sediment accumulation factors.
AB  - In the early stages of risk assessments for sites with contaminated sediments,
      predictions of risks are often complicated or limited by sparse or inadequate
      bioaccumulation data. These limitations often require risk assessors to estimate
      bioaccumulation relationships in order to complete the assessments of risk. In
      the present study, the errors are evaluated with the simple (direct) application
      of field measured biota-sediment accumulation factors (BSAFs) to other species at
      a specific location, and to the same species and/or other species at other
      locations within a site and to other sites. The median (90th percentile)
      differences in directly applying BSAFs to other species at a specific location
      were < or =2.1x (< or =5.1x) for fish and mussel species groups. The median (90th
      percentile) differences for applications across locations within a site for a
      specific species and to other species were < or =3.3x (< or =10x) for fish,
      mussel, and decapod crustacean groups. For direct application across sites,
      slightly larger median (90th percentile) differences were observed, i.e., < or
      =4.0x (< or =12x). The analysis was performed using a data set of 17,848 BSAFs
      spanning 392 chemicals/chemical combinations and 71 species.

PMID- 20821440
TI  - An evaluation of mercury concentrations in three brands of canned tuna.
AB  - There is widespread concern over the presence of Hg in fish consumed by humans.
      While studies have been focused on determining the Hg concentration in sport fish
      and some commercial fish, little attention has been directed to canned tuna; it
      is widely held that concentrations are low. In the present study, the amount of
      Hg present in canned tuna purchased in Las Vegas, Nevada, USA, was examined, and
      the brand, temporal variation, type, and packaging medium impacts on Hg
      concentrations in tuna were explored. A significant (p < 0.001) brand difference
      was noted: Brand 3 contained higher Hg concentrations ($?bar x$ standard
      deviation (SD) (0.777 +/- 0.320 ppm) than Brands 1 (0.541 +/- 0.114 ppm) and 2
      (0.550 +/- 0.199 ppm). Chunk white tuna (0.619 +/- 0.212 ppm) and solid white
      tuna (0.576 +/- 0.178 ppm) were both significantly (p < 0.001) higher in mean Hg
      than chunk light tuna (0.137 +/- 0.063 ppm). No significant temporal variation
      was noted, and packaging had no significant effect on Hg concentration. In total,
      55% of all tuna examined was above the U.S. Environmental Protection Agency's
      (U.S. EPA) safety level for human consumption (0.5 ppm), and 5% of the tuna
      exceeded the action level established by the U.S. Food and Drug Administration
      (U.S. FDA) (1.0 ppm). These results indicate that stricter regulation of the
      canned tuna industry is necessary to ensure the safety of sensitive populations
      such as pregnant women, infants, and children. According to the U.S. EPA
      reference dose of 0.1 microg/kg body weight per day and a mean Hg value of 0.619
      ppm, a 25-kg child may consume a meal (75 g) of canned chunk white tuna only once
      every 18.6 d. Continued monitoring of the industry and efforts to reduce Hg
      concentrations in canned tuna are recommended. Environ.

PMID- 20821441
TI  - Polybrominated diphenyl ethers, toxaphenes, and other halogenated organic
      pollutants in great blue heron eggs.
AB  - The great blue heron (Ardea herodias) has been used as a bioindicator of the
      state of the St. Lawrence River (Quebec, Canada) since 1996. At 5-year intervals,
      selected breeding colonies along the River and its estuary are visited to
      estimate reproductive success and determine levels of contamination. Brominated
      flame retardants are found in many ecosystems and are increasing in concentration
      in the Great Lakes, which is the source of much of the water for the St. Lawrence
      River. In 2001 and 2002, in addition to polychlorinated biphenyls (PCBs) and
      chlorinated pesticides, the levels of polybrominated diphenyl ethers (PBDEs),
      polychlorinated bornanes (toxaphene) congeners and non-ortho-substituted PCBs
      were measured for the first time in pools of great blue heron eggs. The PBDE
      levels in great blue heron eggs (70-1,377 ng/g wet wt) were comparable to those
      measured in herring gull (Larus argentatus) eggs from the Great Lakes. Toxaphene
      was detected in great blue heron eggs at levels comparable to those of other
      major chlorinated pesticides. Major toxaphene congeners were octachlorobornane
      P44 and the nonachlorobornane P50. Environ.

PMID- 20821442
TI  - Phage display as a novel screening tool for primary toxicological targets.
AB  - In the present study the use of phage display as a screening tool to determine
      primary toxicological targets was investigated. These primary toxicological
      targets are the targets in the cell with which a chemical compound initially
      interacts and that are responsible for consecutive (toxic) effects. Nickel was
      used as model compound for the present study. By selection of Ni-binding peptides
      out of a 12-mer peptide phage library, it was possible to identify primary
      toxicological targets of Ni (and other metals). The selected Ni-binding peptides
      showed similarities to important primary toxicological targets of Ni, such as the
      hydrogenase nickel incorporation protein (hypB) and the Mg/Ni/Co transporter
      (corA). This shows that phage display, which is already widely used in other
      research fields, also has potential in ecotoxicology, as a novel screening tool
      with which to determine primary toxicological targets of chemical compounds.

PMID- 20821443
TI  - Sulfate reduction, molecular diversity, and copper amendment effects in bacterial
      communities enriched from sediments exposed to copper mining residues.
AB  - Sulfate-reducing bacterial communities from coastal sediments with a long-term
      exposure to copper (Cu)-mining residues were studied in lactate enrichments. The
      toxicity of excess copper may affect sulfate-reducing bacterial communities.
      Sulfate reduction was monitored by sulfate and organic acid measurements.
      Molecular diversity was analyzed by 16S rRNA, dissimilatory sulfate reduction
      dsrAB, and Cu translocating phospho-type adenosine triphosphatases (P-ATPases)
      cop-like gene sequence profiling. The influence of Cu amendment was tested in
      these enrichments. Results showed fast sulfate reduction mostly coupled to
      incomplete organic carbon oxidation and partial sulfate reduction inhibition due
      to copper amendment. The 16S rRNA clonal libraries analysis indicated that delta-
      and gamma-Proteobacteria and Cytophaga-Flexibacter-Bacteroides dominated the
      enrichments. The dsrAB libraries revealed the presence of Desulfobacteraceae and
      Desulfovibrionaceae families-related sequences. Copper produced significant
      shifts (i.e., a decrease in the relative abundance of sulfate-reducing
      microorganisms) in the enriched bacterial community structure as determined by
      terminal-restriction fragment length polymorphism (T-RFLP) profiling and
      multivariate analyses. Clonal libraries of cop-like sequences showed low richness
      in the enriched microbial communities, and a strong effect of copper on its
      relative abundance. Novel Cu-P(IB)-ATPase sequences encoding Cu resistance were
      detected. The present study indicates that Cu does not significantly affect
      sulfate reduction and genetic diversity of taxonomic and dissimilatory sulfate
      reduction molecular markers. However, the diversity of Cu resistance genetic
      determinants was strongly modified by this toxic metal.

PMID- 20821444
TI  - Exchange of polycyclic aromatic hydrocarbons among the atmosphere, water, and
      sediment in coastal embayments of southern California, USA.
AB  - The present study investigated cross-media transport between both the sediment
      and the water column and between the water column and the atmosphere, to
      understand the role of each compartment as a source or a sink of polycyclic
      aromatic hydrocarbons (PAH) in southern California, USA, coastal waters.
      Concentrations of PAH were measured in the atmosphere, water column, and sediment
      at four water-quality-impaired sites in southern California: Ballona Creek
      Estuary, Los Angeles Harbor, Upper Newport Bay, and San Diego Bay. These
      concentrations were used to calculate site-specific sediment-water and atmosphere
      water exchange fluxes. The net sediment-water exchange of total PAH (t-PAH) was
      positive, indicating that sediments were a source to the overlying water column.
      Furthermore, the net atmosphere-water exchange (gas exchange + dry particle
      deposition) of t-PAH was typically positive also, indicating the water column was
      a net source of PAH to the surrounding atmosphere through gas exchange. However,
      in all cases, the magnitude of the diffusive flux of PAH out of the sediments and
      into the water column far exceeded input or output of PAH through air/water
      exchange processes. These results demonstrate the potential importance of
      contaminated sediments as a source of PAH to the water column in coastal waters
      of southern California.

PMID- 20821445
TI  - Fecal genotyping and contaminant analyses reveal variation in individual river
      otter exposure to localized persistent contaminants.
AB  - The present study investigated polyhalogenated aromatic hydrocarbon (PHAH)
      concentrations in feces of known river otters (Lontra canadensis) along the coast
      of southern Vancouver Island, British Columbia, Canada. Specifically, we combined
      microsatellite genotyping of DNA from feces for individual identification with
      fecal contaminant analyses to evaluate exposure of 23 wild otters to
      organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and
      polybrominated diphenylethers (PBDEs). Overall, feces collected from otters in
      urban/industrial Victoria Harbor had the greatest concentrations of nearly all
      compounds assessed. Fecal concentrations of OCPs and PBDEs were generally low
      throughout the region, whereas PCBs dominated in all locations. Re-sampling of
      known otters over space and time revealed that PCB exposure varied with movement
      and landscape use. Otters with the highest fecal PCB concentrations were those
      inhabiting the inner reaches of Victoria Harbor and adjacent Esquimalt Harbor,
      and those venturing into the harbor systems. Over 50% of samples collected from
      eight known otters in Victoria Harbor had total-PCB concentrations above the
      maximum allowable concentration as established for Eurasian otter (Lutra lutra)
      feces, with a geometric mean value (10.6 mg/kg lipid wt) that exceeded the
      reproductive toxicity threshold (9 mg/kg lipid wt). Those results are consistent
      with our findings from 1998 and 2004, and indicate that the harbors of southern
      Vancouver Island, particularly Victoria Harbor, are a chronic source of PCB
      exposure for otters. The present study further demonstrates the suitability of
      using otter feces as a noninvasive/destructive biomonitoring tool in contaminant
      studies, particularly when sampling of the same individuals at the local
      population-level is desired.

PMID- 20821446
TI  - Fate of trace organic compounds during vadose zone soil treatment in an onsite
      wastewater system.
AB  - During onsite wastewater treatment, trace organic compounds are often present in
      the effluents applied to subsurface soils for advanced treatment during vadose
      zone percolation and groundwater recharge. The fate of the endocrine-disrupting
      surfactant metabolites 4-nonylphenol (NP), 4-nonylphenolmonoethoxylate (NP1EO),
      and 4-nonylphenolmonoethoxycarboxylate (NP1EC), metal-chelating agents
      ethylenediaminetetraacetic acid (EDTA) and nitrilotriacetic acid (NTA),
      antimicrobial agent triclosan, stimulant caffeine, and antibiotic
      sulfamethoxazole during transport through an unsaturated sandy loam soil was
      studied at a field-scale test site. To assess the effects of effluent quality and
      hydraulic loading rate (HLR) on compound fate in the soil profile, two effluents
      (septic tank or textile biofilter) were applied at two design HLRs (2 or 8 cm/d).
      Chemical concentrations were determined in the two effluents and soil pore water
      at 60, 120, and 240 cm below the soil infiltrative surface. Concentrations of
      trace organic compounds in septic tank effluent were reduced by more than 90%
      during transport through 240 cm (often within 60 cm) of soil, likely due to
      sorption and biotransformation. However, the concentration of NP increased with
      depth in the shallow soil profile. Additional treatment of anaerobic septic tank
      effluent with an aerobic textile biofilter reduced effluent concentrations of
      many compounds, but generally did not affect any changes in pore water
      concentrations. The soil profile receiving septic tank effluent (vs. textile
      biofilter effluent) generally had greater percent removal efficiencies. EDTA, NP,
      NP1EC, and sulfamethoxazole were measured in soil pore water, indicating the
      ability of some trace organic compounds to reach shallow groundwater. Risk is
      highly dependent on the degree of further treatment in the saturated zone and the
      types and proximity of uses for the receiving groundwater environment.

PMID- 20821447
TI  - Copper toxicity thresholds in Chinese soils based on substrate-induced
      nitrification assay.
AB  - Copper toxicity in 17 Chinese soils was screened using a substrate-induced
      nitrification assay to generate information for the development of a terrestrial
      biotic ligand model (tBLM). The leaching effect on the Cu toxicity thresholds was
      investigated. Both the total Cu-based median effective concentration (EC50)
      values (46.9-2726 mg/kg) and the solution Cu-based EC50 values (0.04-2.91 mg/L)
      in unleached soils varied substantially among the soils in the present study. For
      unleached soils, linear stepwise multiple regression analysis showed that total
      Ca and soil pH were the best predictors for total Cu-based EC50, while electrical
      conductivity (EC) and soil pH were the best predictors for solution Cu-based
      EC50. The variation in solution Cu-based EC50 was largely (R(2) = 0.75) explained
      by Mg but not Ca and H(+) concentration in soil solution at EC50, suggesting a
      protective effect of Mg(2+) against Cu toxicity in the test soils. Leaching
      impacted Cu toxicity differently among the soils and apparently reduced the
      variations of both the total Cu-based and the solution Cu-based EC50. The
      predictability of the Cu EC50 by empirical models was decreased after leaching.
      The leaching effect on Cu toxicity, indicated by a leaching factor, was not
      predicted by any soil properties. There is a need to investigate quantitatively
      the mechanisms for the leaching effect on Cu toxicity in soils.

PMID- 20821448
TI  - Effects of environmental regimens on the toxin profile of Alexandrium
      ostenfeldii.
AB  - Environmental conditions are key factors in the development of marine toxic
      phytoplankton. Spirolides are marine toxins with a heptacyclic imine ring
      responsible for the toxicity in mice. Alexandrium ostenfeldii (A. ostenfeldii) is
      the main producer of these toxins, although this dinoflagellate often produces
      toxins belonging to the paralytic shellfish poisoning (PSP) group. The present
      study shows the first evidence that external environmental factors can influence
      the toxin profile produced by the dinoflagellate A. ostenfeldii. The species
      investigated is indigenous to the North Atlantic coast, and their cells grew
      under several environmental parameters. Toxin production was measured by means of
      liquid chromatography-mass spectrometry (LC-MS) and the chromatograms reflect the
      presence of two spirolides in all cultures; one in the region m/z 692.5,
      corresponding to 13-desmethyl spirolide C (13-desMeC) and the other in the region
      m/z 678.5, which corresponds to 13,19-didesmethyl spirolide C (13,19-didesMeC).
      The physical parameters studied were salinity, culture media, and photoperiod.
      The highest amount of toxin per cell was obtained when dinoflagellates grew in
      F/2 and Walne medium, 28 per thousand salinity, and 24 h of light. However, the
      highest proportion of 13,19-didesMeC with respect to 13-desMeC was achieved in L1
      medium, 33 per thousand salinity, and 14:10 h light:dark. On the contrary, the
      highest proportion of 13-desMeC in cells was obtained when A. ostenfeldii was
      cultured in F/2 medium, 28 per thousand salinity, and the same photoperiod.
      Therefore, from these data the optimum conditions to culture A. ostenfeldii and
      to obtain the highest amount of spirolide per cell are shown. In addition, these
      environmental conditions can be considered a tool to predict and avoid A.
      ostenfeldii blooms.

PMID- 20821449
TI  - A comparison of the copper sensitivity of six invertebrate species in ambient
      salt water of varying dissolved organic matter concentrations.
AB  - The copper sensitivity of four saltwater invertebrates (the mussel Mytilus
      galloprovincialis, the oyster Crassostrea virginica, the sand dollar Dendraster
      excentricus, and the sea urchin Strongylocentrotus purpuratus) was determined
      experimentally using chronic-estimator embryo-larval test procedures. The effect
      of sample dissolved organic matter (DOM) content on Cu bioavailability was
      determined for these species using commonly prescribed test procedures.
      Comparisons were made among these test results and test results reported
      previously for two other invertebrate species: the mussel Mytilus edulis and the
      copepod Eurytemora affinis. All six species exhibited a direct and significant
      relationship between the sample dissolved organic carbon (DOC; a surrogate
      measure of DOM) and either the dissolved Cu median lethal concentration (LC50)
      values or median effect concentration (EC50) values. This relationship is
      significant even when the DOM has different quality as evidenced by molecular
      fluorescence spectroscopy. Once normalized for the effects of DOM, the Cu
      sensitivity of these species from least to most sensitive were E. affinis < D.
      excitricus < C. virginica approximately S. purpuratus approximately M. edulis
      approximately M. galloprovincialis. This ranking of species sensitivity differs
      from the saltwater species sensitivity distribution proposed in 2003 by the U.S.
      Environmental Protection Agency. These results support the need to account for
      factors that modify Cu bioavailability in future saltwater Cu criteria
      development efforts. More specifically, Cu saltwater species sensitivity
      distribution data will need to be normalized by factors affecting Cu
      bioavailability to assure that accurate and protective criteria are subsequently
      developed for saltwater species and their uses.

PMID- 20821450
TI  - Evaluation of metal toxicity by a modified method based on the fungus Gerronema
      viridilucens bioluminescence in agar medium.
AB  - Metal cation toxicity to basidiomycete fungi is poorly understood, despite its
      well-known importance in terrestrial ecosystems. Moreover, there is no reported
      methodology for the routine evaluation of metal toxicity to basidiomycetes. In
      the present study, we describe the development of a procedure to assess the acute
      toxicity of metal cations (Na(+), K(+), Li(+), Ca(2+),Mg(2+), Co(2+), Zn(2+),
      Ni(2+), Mn(2+), Cd(2+), and Cu(2+)) to the bioluminescent basidiomycete fungus
      Gerronema viridilucens. The method is based on the decrease in the intensity of
      bioluminescence resulting from injuries sustained by the fungus mycelium exposed
      to either essential or nonessential metal toxicants. The assay described herein
      enables us to propose a metal toxicity series to Gerronema viridilucens based on
      data obtained from the bioluminescence intensity (median effective concentration
      [EC50] values) versus metal concentration: Cd(2+) > Cu(2+) > Mn(2+) approximately
      Ni(2+) approximately Co(2+) > Zn(2+) > Mg(2+) > Li(+) > K(+) approximately Na(+)
      > Ca(2+), and to shed some light on the mechanism of toxic action of metal
      cations to basidiomycete fungi.

PMID- 20821451
TI  - Measuring variability in phytotoxicity testing using crop and wild plant species.
AB  - A series of experiments was conducted to assess the level of variability in
      phytotoxicity testing and to investigate factors that may explain some of the
      observed uncertainties and inconsistencies. The work was conducted in greenhouse
      or growth chamber environments with plants growing individually in pots and
      harvested 28 d after spraying with two herbicides, glyphosate and atrazine, as
      formulated products. Between six and 10 doses were used on five or six
      replicates, necessitating over 4,500 individually growing plants. In the first
      set of experiments, several ecotypes (originating from different areas of the
      world) of eight wild plant species were tested. Significant differences in
      sensitivity to atrazine and glyphosate were found among ecotypes of most species
      tested. In the second suite of experiments, the reproducibility of results during
      different seasons (when growing conditions vary) was investigated using three
      crops and four wild plant species. Results showed that seasonal variability
      elicited a pronounced discrepancy in response between plants tested at different
      times of the year. It was found that no consistent effects could be attributed to
      the biotic or abiotic factors investigated. Several ecotypes of the same species
      differed in their seed size, percentage germination, or germination requirements,
      as well as in growth patterns, but these differences could not explain
      differences in herbicide sensitivity. Likewise, differences in phytotoxicity
      could not be attributed to factors such as temperature, light intensity, and
      sunlight duration. The present study supports the inclusion of an uncertainty
      factor in risk assessments to account for the intrinsic variability in plant
      sensitivity to herbicides.

PMID- 20821452
TI  - Toxicity of methyl tert butyl ether to soil invertebrates (springtails: Folsomia
      candida, Proisotoma minuta, and Onychiurus folsomi) and lettuce (Lactuca sativa).
AB  - Experiments were conducted to assess the toxicity of methyl tert butyl ether
      (MTBE) to three species of Collembola (Proisotoma minuta, Folsomia candida, and
      Onychiurus folsomi) and lettuce (Lactuca sativa L.) using an artificial
      Organization for Economic Cooperation and Development (OECD) soil and field
      collected sandy loam and silt loam soil samples. Soil invertebrate tests were
      carried out in airtight vials to prevent volatilization of MTBE out of the test
      units and to allow for direct head-space sampling and gas chromatography-mass
      spectrometry (GC-MS) analysis for residual MTBE. The use of the airtight vial
      protocol proved to be very successful, in that the measured MTBE concentrations
      at the beginning of the experiments were within 95% of nominal concentrations.
      The test methods used in this study could be used to test the toxicity of other
      volatile organic compounds to Collembola. The soil invertebrates tested had
      inhibitory concentration (ICx) and lethal concentration (LCx) values that ranged
      from 242 to 844 mg MTBE/kg dry soil. When the three test species of Collembola
      were tested under identical conditions in the artificial OECD soil, O. folsomi
      was the most sensitive collembolan, with a median inhibitory concentration (IC50;
      reproduction) of 296 mg MTBE/kg dry soil. The most sensitive endpoint for lettuce
      was an IC50 for root length of 81 mg MTBE/kg dry soil after 5 d of germination in
      OECD soil. Data on the loss of MTBE from the three test soils over time indicated
      that MTBE was retained in the silt loam soil longer than in either the sandy loam
      or the artificial OECD soil.

PMID- 20821453
TI  - Observed and predicted reproduction of Ceriodaphnia dubia exposed to chloride,
      sulfate, and bicarbonate.
AB  - Chronic toxicities of Cl(-), SO(4) (2-), and HCO(3) (-) to Ceriodaphnia dubia
      were evaluated in low- and moderate-hardness waters using a three-brood
      reproduction test method. Toxicity tests of anion mixtures were used to determine
      interaction effects and to produce models predicting C. dubia reproduction.
      Effluents diluted with low- and moderate-hardness waters were tested with animals
      acclimated to low- and moderate-hardness conditions to evaluate the models and to
      assess the effects of hardness and acclimation. Sulfate was significantly less
      toxic than Cl(-) and HCO(3) (-) in both types of water. Chloride and HCO(3) (-)
      toxicities were similar in low-hardness water, but HCO(3) (-) was the most toxic
      in moderate-hardness water. Low acute-to-chronic ratios indicate that toxicities
      of these anions will decrease quickly with dilution. Hardness significantly
      reduced Cl(-) and SO(4) (2-) toxicity but had little effect on HCO(3) (-).
      Chloride toxicity decreased with an increase in Na(+) concentration, and HCO(3) (
      ) toxicity may have been reduced by the dissolved organic carbon in effluent.
      Multivariate models using measured anion concentrations in effluents with low to
      moderate hardness levels provided fairly accurate predictions of reproduction.
      Determinations of toxicity for several effluents differed significantly depending
      on the hardness of the dilution water and the hardness of the water used to
      culture test animals. These results can be used to predict the contribution of
      elevated anion concentrations to the chronic toxicity of effluents; to identify
      effluents that are toxic due to contaminants other than Cl(-), SO(4) (2-), and
      HCO(3) (-); and to provide a basis for chemical substitutions in manufacturing
      processes.

PMID- 20821454
TI  - The toxic effects of benzyl glucosinolate and its hydrolysis product, the
      biofumigant benzyl isothiocyanate, to Folsomia fimetaria.
AB  - Natural isothiocyanates (ITCs) are toxic to a range of pathogenic soil-living
      species, including nematodes and fungi, and can thus be used as natural fumigants
      called biofumigants. Natural isothiocyanates are hydrolysis products of
      glucosinolates (GSLs) released from plants after cell rupture. The study
      investigated the toxic effects of benzyl-GSL and its hydrolysis product benzyl
      ITC on the springtail Folsomia fimetaria, a beneficial nontarget soil-dwelling
      micro-arthropod. The soil used was a sandy agricultural soil. Half-lives for
      benzyl-ITC in the soil depended on the initial soil concentration, ranging from
      0.2 h for 67 nmol/g to 13.2 h for 3,351 nmol/g. For benzyl-ITC, the concentration
      resulting in 50% lethality (LC50) value for F. fimetaria adult mortality was 110
      nmol/g (16.4 mg/kg) and the concentration resulting in 50% effect (EC50) value
      for juvenile production was 65 nmol/g (9.7 mg/kg). Benzyl-GSL proved to be less
      toxic and consequently an LC50 value for mortality could not be estimated for
      springtails exposed to benzyl-GSL. For reproduction, an EC50 value was estimated
      to approximately 690 nmol/g. The study indicates that natural soil concentrations
      of ITCs may be toxic to beneficial nontarget soil-dwelling arthropods such as
      springtails.

PMID- 20821456
TI  - Mercury and other metals in muscle and ovaries of goldeye (Hiodon alosoides).
AB  - Concentrations of 24 trace metals were assessed in gravid ovaries and in muscle
      of female juvenile and adult female goldeye (Hiodon alosoides), a fish with both
      low annual growth (16 g/year as adults) and a long life span (maximum longevity
      of 30 years). It was hypothesized that adult fish with these life-history
      characteristics would maintain stable concentrations of metals in their tissues
      with higher levels of essential elements compared with those that are potentially
      toxic. As hypothesized, the concentration of most metals in muscle of adult
      female goldeye was similar at all ages, suggesting that uptake and excretion of
      metals was equal. Mercury was a notable exception. Total Hg concentrations in
      muscle of adults increased throughout life from a mean of 206 ng/g wet weight at
      age 8 to 809 ng/g at age 28, or by 26.2 ng/g/year. Concentrations of Hg were low
      in ovaries (mean 21.1 ng/g wet wt) compared to the mean for muscle, only 7% of
      the concentration in muscle. This was the lowest percent of muscle concentration
      of all 24 metals. Concentrations of Al, Ba, La, V, and Mn were significantly
      greater in muscle of juveniles and in ovaries than in muscle of adults.
      Concentrations of 13 metals were higher in ovaries relative to muscle, seven were
      similar, and four were depleted. Silver was enriched by over 50-fold in ovaries.
      Overall, the present study suggests that low concentrations of some metals in
      muscle of adult female goldeye, relative to concentrations in female juveniles
      and ovaries, may be maintained in part by transfer of metals to the external
      environment in eggs at spawning.

PMID- 20821455
TI  - Effects of dietary cadmium exposure on reproduction of saltwater cladoceran Moina
      monogolica Daday: Implications in water quality criteria.
AB  - The chronic toxicity of dietary cadmium to the saltwater cladoceran Moina
      monogolica Daday and its relative toxicity compared with aquatic exposure were
      investigated in the present study. The microalgae Chlorella pyrenoidosa, exposed
      to cadmium in growth inhibition tests, had a 96-h median effective concentration
      (EC50) of 81.2 microg Cd/L (95% confidence intervals [CIs] = 71.9-95.1). C.
      pyrenoidosa exposed for 96 h to sublethal dissolved cadmium concentrations in the
      range 4.10 +/- 0.30 to 70.29 +/- 0.31 microg/L resulted in algal cadmium burdens
      up to 73.86 x 10(-16) g Cd/cell. Cellular cadmium burdens accumulated in a dose
      dependent manner, whereas cell densities inversely declined from 670 x 10(4) to
      38 x 10(4) cells/ml with exposure to the increasing aqueous cadmium
      concentrations. C. pyrenoidosa preexposed to cadmium and used as food in a
      chronic 21-d toxicity test with the cladoceran M. monogolica, containing no added
      dissolved cadmium, inhibited reproduction. Significant reductions of the net
      reproduction rate (R(0)) per brood were observed in all broods, and the decline
      in the number of neonates produced increased with each subsequent brood. The
      cadmium concentration (4.10 +/- 0.30 microg/L) in the algal culture water that
      produced the lowest algal cadmium burden (2.85 +/- 0.76 x 10(-16) g Cd/cell) was
      shown to inhibit M. monogolica reproduction and was compared with the water
      quality criteria (WQC) of China. This comparison indicated that dietary exposure
      to cadmium may cause sublethal responses at concentrations below the current
      cadmium WQC of China for aquaculture.

PMID- 20821457
TI  - C-fin: a cultured frog tadpole tail fin biopsy approach for detection of thyroid
      hormone-disrupting chemicals.
AB  - There is a need for the development of a rapid method for identifying chemicals
      that disrupt thyroid hormone (TH) action while maintaining complex tissue
      structure and biological variation. Moreover, no assay to date allows a
      simultaneous screen of an individual's response to multiple chemicals. A cultured
      tail fin biopsy or C-fin assay was developed using Rana catesbeiana tadpoles.
      Multiple tail fin biopsies were taken per tadpole, cultured in serum-free medium,
      and then each biopsy was exposed to a different treatment condition. The effects
      of known disruptors of TH action were evaluated in the C-fin assay. Chemical
      exposure was performed +/- 10 nM 3,3',5-triiodothyronine and real-time
      quantitative polymerase chain reaction (QPCR) of two TH-responsive transcripts,
      TH receptor beta (TRbeta) and the Rana larval keratin type I (RLKI), was
      performed. Within 48 h of exposure to Triac (1-100 nM), roscovitine (0.6-60
      microM), or genistein (1-100 microM), perturbations in TH signaling were
      detected. Tetrabromobisphenol A (TBBPA) (10-1,000 nM) showed no effect.
      Acetochlor (1-100 nM) elicited a modest effect on the TH-dependent induction of
      TRbeta transcript. These data reveal that a direct tissue effect may not be
      critical for TBBPA and acetochlor to disrupt TH action previously observed in
      intact tadpoles.

PMID- 20821458
TI  - Predicting mercury concentrations in mallard eggs from mercury in the diet or
      blood of adult females and from duckling down feathers.
AB  - Measurements of Hg concentrations in avian eggs can be used to predict possible
      harm to reproduction, but it is not always possible to sample eggs. When eggs
      cannot be sampled, some substitute tissue, such as female blood, the diet of the
      breeding female, or down feathers of hatchlings, must be used. When female
      mallards (Anas platyrhynchos) were fed diets containing methylmercury chloride,
      the concentration of Hg in a sample of their blood was closely correlated with
      the concentration of Hg in the egg they laid the day they were bled (r2 = 0.88; p
      < 0.001). Even when the blood sample was taken more than two weeks after an egg
      was laid, there was a strong correlation between Hg concentrations in female
      blood and eggs (r2 = 0.67; p < 0.0002). When we plotted the dietary
      concentrations of Hg we fed to the egg-laying females against the concentrations
      of Hg in their eggs, the r2 value was 0.96 (p < 0.0001). When the concentrations
      of Hg in the down feathers of newly hatched ducklings were plotted against Hg in
      the whole ducklings, the r2 value was 0.99 (p < 0.0003). Although measuring Hg in
      eggs may be the most direct way of predicting possible embryotoxicity, our
      findings demonstrate that measuring Hg in the diet of breeding birds, in the
      blood of egg-laying females, or in down feathers of hatchlings all can be used to
      estimate what concentration of Hg may have been in the egg.

PMID- 20821459
TI  - Ranking sediment samples from three Spanish estuaries in relation to its toxicity
      for two benthic species: the microalga Cylindrotheca closterium and the copepod
      Tisbe battagliai.
AB  - The present study assesses the sediment toxicity levels of three Spanish
      estuaries, as well as the suitability of two microorganisms, the benthic
      microalga Cylindrotheca closterium and the harpacticoid copepod Tisbe battagliai,
      as test organisms in whole-sediment toxicity assays. The sensitivity of both
      species to potentially polluted sediments was compared. Three sites at the
      southwest of the Iberian Peninsula were chosen: the Ria of Huelva, the
      Guadalquivir Estuary, and the Bay of Algeciras. Inhibition data were based on
      growth for C. closterium and fecundity for T. battagliai. No toxicity was
      recorded for the microalga in the Guadalquivir Estuary and the Bay of Algeciras.
      However, for T. battagliai, inhibition of fecundity was approximately 50% in
      those zones, indicating higher sensitivity. Samples from stations in the Ria of
      Huelva were the most toxic of all those assayed; inhibition values higher than
      90% were obtained for both organisms. The highest values for total metal
      concentrations such as arsenic (As), cadmium (Cd), copper (Cu), iron (Fe), lead
      (Pb), tin (Sn), and zinc (Zn) were found in the Ria of Huelva, which can be
      classified as severely impacted. The Guadalquivir Estuary and the Bay of
      Algeciras can be considered moderately impacted. In general, both methodologies
      are suitable for application in ecotoxicological studies.

PMID- 20821460
TI  - The influence of diet on the assimilation efficiency of 47 polychlorinated
      biphenyl congeners in Japanese koi (Cyprinus carpio).
AB  - The influence of diet on polychlorinated biphenyl (PCB) assimilation was
      investigated by measuring dietary assimilation efficiencies (AEs) for 47 PCB
      congeners in juvenile koi (Cyprinus carpio) fed five experimental diets. Two of
      the diets were naturally contaminated and were obtained by collecting mayflies
      from Lake Erie (ON, Canada) and emerald shiners from the Detroit River (MI, USA).
      The remaining diets consisted of commercial fish pellets (lipid contents from 6.7
      to 24%) that were contaminated by spiking with a PCB mixture. Experimental fish
      were held individually to quantify the amount of food consumed per fish and,
      following a 48-h fasting period to facilitate food digestion and assimilation;
      AEs were determined by mass balance. Fish fed the benthic invertebrate food
      exhibited the highest PCB AEs (70-101%) and were significantly elevated compared
      to the other diet treatments (AEs ranging from 23 to 87%). The PCB AEs for fish
      fed emerald shiners did not differ from those fed pellet formulations. Variation
      among PCB AEs was not related to diet lipid content. For all diet treatments, PCB
      AEs were significantly related to chemical hydrophobicity. The relationship
      between chemical AE and n-octanol/water partition coefficient (K(OW)) was best
      explained by a linear model compared to a two-phase resistance model. Overall,
      PCB AEs were observed to be dependent on both diet type and chemical
      hydrophobicity, with both factors contributing nearly equally to the variation
      measured in this toxicokinetic parameter.

PMID- 20821461
TI  - Aquatic toxicity of magnesium sulfate, and the influence of calcium, in very low
      ionic concentration water.
AB  - The toxicity of magnesium sulfate (MgSO(4)), and the influence of calcium (Ca),
      were assessed in very soft freshwater (natural Magela Creek water [NMCW]) using
      six freshwater species (Chlorella sp., Lemna aequinoctialis, Amerianna cumingi,
      Moinodaphnia macleayi, Hydra viridissima, and Mogurnda mogurnda). The study
      involved five stages: toxicity of MgSO(4) in NMCW, determination of the toxic
      ion, influence of Ca on Mg toxicity, toxicity of MgSO(4) at an Mg:Ca mass ratio
      of 9:1, and derivation of water quality guideline values for Mg. The toxicity of
      MgSO(4) was higher than previously reported, with chronic median inhibition
      concentration (IC50)/acute median lethal concentration (LC50) values ranging from
      4 to 1,215 mg/L, as Mg. Experiments exposing the 3 most sensitive species (L.
      aequinoctialis, H. viridissima, and A. cumingi) to Na(2)SO(4) and MgCl(2)
      confirmed that Mg was the toxic ion. Additionally, Ca was shown to have an
      ameliorative effect on Mg toxicity. For L. aequinoctialis and H. viridissima, Mg
      toxicity at the IC50 concentration was eliminated at Mg:Ca (mass) ratios of < or
      =10:1 and < or =9:1, respectively. For A. cumingi, a 10 to 30% effect persisted
      at the IC50 concentration at Mg:Ca ratios <9:1. The toxicity of MgSO(4) in NMCW
      at a constant Mg:Ca ratio of 9:1 was lower than at background Ca, with chronic
      IC50/acute LC50 values from 96 to 4,054 mg/L, as Mg. Water quality guideline
      values for Mg (to protect 99% of species) at Mg:Ca mass ratios of >9:1 and < or
      =9:1 were 0.8 and 2.5 mg/L, respectively. Magnesium can be toxic at
      concentrations approaching natural background levels, but toxicity is dependent
      on Ca concentrations, with exposure in very low ionic concentration, Ca-deficient
      waters posing the greatest risk to aquatic life.

PMID- 20821462
TI  - Sediment toxicity and bioaccumulation of nano and micron-sized aluminum oxide.
AB  - Nano-aluminum oxide (Al(2)O(3)) is used commercially in coatings and abrasives.
      Nano-Al(2)O(3) can also be generated through the oxidation of nano-aluminum in
      military propellants and energetics. The purpose of the present study was to
      assess toxicity and bioaccumulation of nano-Al(2)O(3) to a variety of sediment
      organisms (Tubifex tubifex, Hyalella azteca, Lumbriculus variegatus, and
      Corbicula fluminea). The bioaccumulation and toxicity of nano-Al(2)O(3) was
      compared with that of micron-sized Al(2)O(3) to investigate potential size
      related effects. Results of the present study show species-specific differences
      in relative bioaccumulation of nano and micron-sized Al(2)O(3). Significant toxic
      effects (survival and growth) were observed in H. azteca testing, but only at
      high concentrations unlikely to be found in the environment. Nano-Al(2)O(3) was
      found to be more toxic than micron-sized Al(2)O(3) to H. azteca survival in a 14
      d study in which organisms were in direct contact with a thin layer of 625 or
      2,500 mg of Al(2)O(3) dispersed on the surface of either sediment or sand. A
      significant growth effect was also observed for nano but not micron-sized
      Al(2)O(3) at the highest treatment level tested (100 g/kg Al(2)O(3)) in a 10-d H.
      azteca bioassay in which Al(2)O(3) was homogenized with sediment. However,
      differences in measured sediment Al concentrations (micron-sized = 55.1 [+/-0.6]
      g/kg Al; nano-sized = 66.2 [+/-0.6] g/kg Al) in the nano and micron-sized
      Al(2)O(3) preclude direct comparison of the toxicity of these two treatments
      based on particle size.

PMID- 20821463
TI  - Pulp and paper mill effluents induce distinct gene expression changes linked to
      androgenic and estrogenic responses in the fathead minnow (Pimephales promelas).
AB  - Although effluent treatment systems within pulp and paper mills remove many
      toxicants and improve wastewater quality, there is a need to understand and
      quantify the effectiveness of the treatment process. At a combined news and kraft
      pulp and paper mill in northwestern Ontario, Canada, fathead minnow (FHM)
      reproduction and physiology were examined before, during, and after a short-term
      (6-d) exposure to 10% (v/v) untreated kraft mill effluent (UTK), 25% (v/v)
      secondary treated kraft mill effluent (TK), and 100% (v/v) combined mill outfall
      (CMO). Although UTK exposure significantly decreased egg production, neither TK
      nor CMO caused any reproductive changes. The expression of six genes responsive
      to endocrine-disrupting compounds, stress, or metals was then examined in livers
      of these fish using real-time polymerase chain reaction. In female FHMs, none of
      the three effluents induced significant expression changes in any genes
      investigated. By contrast, in males there were significant increases in the mRNA
      levels of androgen receptor, estrogen receptor (ER) beta, and cytochrome P4501A
      (CYP1A) upon UTK and TK exposure but no changes in ERalpha or vitellogenin (VTG)
      gene expression, whereas CMO exposure significantly increased the mRNA levels of
      ERalpha, VTG, and CYP1A. Together, these results suggest that kraft effluent
      before and after biological treatment contained compounds able to induce
      androgenic effects in FHMs, and that combination of kraft and newsmill effluents
      eliminated the androgenic compounds while inducing distinct and significant
      patterns of gene expression changes that were likely due to estrogenic compounds
      produced by the newsmill.

PMID- 20821464
TI  - Effects of pulp and paper mill effluent on fish: a temporal assessment of fish
      health across sampling cycles.
AB  - The Canadian environmental effects monitoring (EEM) program is a regulated,
      cyclical, industry-funded program designed to determine whether receiving water
      impacts exist when a mill is in compliance with its discharge limits. The results
      from three cycles of the fish monitoring program (1992 to 2004) are available
      from over 200 surveys of fish compared between sites located upstream and
      downstream of pulp and paper mill effluent outfalls. Previous meta-analyses have
      shown a national average response pattern across cycles characterized by an
      increase in endpoints measuring energy storage and growth and a decrease in a
      reproductive endpoint, consistent with a response of nutrient enrichment in
      combination with some form of metabolic disruption. Although the national average
      pattern of effects was temporally consistent, there was some variability in the
      magnitude of effects among cycles. Questions were raised as to whether the
      intercycle variability was due to changes in effluent quality or due, at least in
      part, to other factors. The present study compares responses over the first three
      cycles, and shows that the choice of sentinel species is likely to be a major
      contributing factor to the variability in observed effects. Subset analyses using
      studies from mills that used the same sentinel species across cycles reveal
      fairly uniform responses and little evidence of significant improvements in
      overall fish health from cycles one to three. However, a meta-analysis using 1991
      data collected from 10 mills before the implementation of the EEM program and
      data from the same mills collected during cycles one to three of the program
      reveal significantly reduced effects on relative liver weight and potential
      improvements in other endpoints.

PMID- 20821465
TI  - Assessing relationships between chemical exposure, parasite infection, fish
      health, and fish ecological status: a case study using chub (Leuciscus cephalus)
      in the Bilina River, Czech Republic.
AB  - Multiple stressor scenarios, as they are relevant in many watersheds, call for
      approaches extending beyond conventional chemical-focused approaches. The present
      study, investigated the fish population, represented by chub (Leuciscus
      cephalus), in the Bilina River (Czech Republic), which is impacted by various
      pollution sources and might pose a risk on the fish population. To confirm or
      reject this hypothesis it was examined whether there exists an association
      between abundance of chub and exposure to toxic chemicals as well as natural
      stressors, represented by parasites, and whether health-related suborganismal
      traits, namely, organ indices, tissue histopathology, and immune parameters,
      would help in revealing relationships between stressor impact and population
      status. Toxic pressure was assessed by the toxic unit approach, which gives an
      integrative estimate of toxic effect concentrations and by measuring the
      biomarkers cytochrome P4501A and vitellogenin, which indicate exposure to
      bioavailable arylhydrocarbon- or estrogen receptor ligands. Parasite pressure was
      estimated by determining abundance and species composition of ecto- and
      endoparasites of chub. Chub abundance was high upstream in the Bilina, low to
      zero in the middle stretches, and increased again downstream. Toxic pressure
      increased in the downstream direction, while parasite intensity decreased in this
      direction. Health status of chub did not differ clearly between up-, middle-, and
      downstream sites. Thus, it appears that neither toxic pressure nor parasite
      pressure nor their combination translates into a change of chub health status. By
      using varied assessment tools, this study provides evidence against a presumed
      causative role of toxicants impairing the fish ecological status of the Bilina
      River.

PMID- 20821466
TI  - Estimating potential risks to terrestrial invertebrates and plants exposed to
      bisphenol A in soil amended with activated sludge biosolids.
AB  - Bisphenol A (BPA) is a high production volume substance primarily used to produce
      polycarbonate plastic and epoxy resins. During manufacture and use, BPA may enter
      wastewater treatment plants. During treatment, BPA may become adsorbed to
      activated sludge biosolids, which may expose soil organisms to BPA if added to
      soil as an amendment. To evaluate potential risks to organisms that make up the
      base of the terrestrial food web (i.e., invertebrates and plants) in accordance
      with international regulatory practice, toxicity tests were conducted with
      potworms (Enchytraeids) and springtails (Collembolans) in artificial soil, and
      six plant types using natural soil. No-observed-effect concentrations (NOEC) for
      potworms and springtails were equal to or greater than 100 and equal to or
      greater than 500 mg/kg (dry wt), respectively. The lowest organic matter
      normalized NOEC among all tests (dry shoot weight of tomatoes) was 37 mg/kg-dry
      weight. Dividing by an assessment factor of 10, a predicted-no-effect
      concentration in soil (PNEC(soil)) of 3.7 mg/kg-dry weight was calculated.
      Following international regulatory guidance, BPA concentrations in soil
      hypothetically amended with biosolids were calculated using published BPA
      concentrations in biosolids. The upper 95th percentile BPA biosolids
      concentration in North America is 14.2 mg/kg-dry weight, and in Europe is 95
      mg/kg-dry weight. Based on recommended biosolids application rates, predicted BPA
      concentrations in soil (PEC(soil)) would be 0.021 mg/kg-dry weight for North
      America and 0.14 mg/kg-dry weight for Europe. Hazard quotients (ratio of
      PEC(soil) and PNEC(soil)) for BPA were all equal to or less than 0.04. This
      indicates that risks to representative invertebrates and plants at the base of
      the terrestrial food web are low if exposed to BPA in soil amended with activated
      sludge biosolids.

PMID- 20821467
TI  - A new method for ranking mode-specific sensitivity of freshwater arthropods to
      insecticides and its relationship to biological traits.
AB  - The problem of how to deal with species sensitivity differences to toxic
      substances has been addressed successfully with the species sensitivity
      distribution (SSD), yet this has not increased understanding about the underlying
      mechanisms of sensitivity. Other researchers have identified the mode of action
      of chemicals and also biological traits of species as determinants for
      sensitivity, yet no systematic approach combines these factors. To achieve this,
      first existing data on organophosphate, carbamate, and pyrethroid toxicity and
      mode of action and also species trait information were mined. Second, we linked
      taxon sensitivity to their traits at the family level to generate empirical and
      mechanistic hypotheses about sensitivity-trait relationships. In this way, a mode
      specific sensitivity (MSS) ranking method was developed, and tested at the
      taxonomic level of family and genus. The application of several quality criteria
      indicated overall confidence in rankings, but confidence in exact taxon rank was
      less certain, due to data insufficiency for certain groups. The MSS rankings were
      found to be applicable for trait-based approaches and were successfully linked to
      existing trait data to identify traits with predictive potential. Although this
      empirical analysis cannot test causality relationships between traits and
      sensitivity, testable hypotheses were generated, for further experimental
      investigation. Single traits as well as combinations of traits can be used to
      predict laboratory sensitivity to the substances tested, although associations
      were not as strong as in previous studies. We conclude that existing trait data
      are not suitable for every trait-based research question and that important
      traits remain to be identified and quantified in relation to the processes of
      toxicity, i.e., the toxicokinetics and toxicodynamics.

PMID- 20821468
TI  - Influence of deltamethrin on nonspecific cellular and humoral defense mechanisms
      in rainbow trout (Oncorhynchus mykiss).
AB  - The influence of deltamethrin on the innate immunity in rainbow trout was
      examined. Fish were immersed in deltamethrin at doses of 1, 2, and 4 microg/L for
      30 min. The results showed that deltamethrin at doses of 2 and 4 microg/L
      decreased phagocytic activity of spleen macrophages and proliferative response of
      pronephros lymphocytes at days 1, 2, and 5 after immersion. Deltamethrin at these
      doses decreased the lysozyme activity, total protein, and immunoglobulin levels
      in serum. The greatest immunosuppressive influence of deltamethrin at dose 4
      microg/L was observed at the end of the study.

PMID- 20821469
TI  - Protein-based electrochemical biosensor for detection of silver(I) ions.
AB  - Silver(I) ions are extremely toxic to aquatic animals. Hence, monitoring of these
      ions in the environment is needed. The aim of the present study was to suggest a
      simple biosensor for silver(I) ions detection. The suggested biosensor is based
      on the modification of a hanging mercury drop electrode (HMDE) by the heavy metal
      binding protein metallothionein (MT) for silver(I) ions detection.
      Metallothionein accumulated for 120 s onto the HMDE surface. After rinsing the
      electrode, the biosensor (MT modified HMDE) was prepared prior to detection of
      silver(I) ions. The biosensor was immersed in a solution containing silver(I)
      ions. These ions were bound to the MT structure. Furthermore, the electrode was
      rinsed and transferred to a pure supporting electrolyte solution, in which no
      interference was present. Under these experimental conditions, other signals
      relating to heavy metals naturally occurring in MT were not detected. This
      phenomenon confirms the strong affinity of silver(I) ions for MT. The suggested
      biosensor responded well to higher silver(I) ion concentrations. The relative
      standard deviation for measurements of concentrations higher than 50 microM was
      approximately 2% (n = 8). In the case of concentrations lower than 10 microM, the
      relative standard deviation increased to 10% (n = 8). The detection limit (3
      signal/noise) for silver(I) ions was estimated as 500 nM.

PMID- 20821470
TI  - Complexes of glutathione with heavy metal ions as a new biochemical marker of
      aquatic environment pollution.
AB  - Reduced glutathione (GSH) plays a number of key roles in many biochemical
      pathways. This peptide is highly reactive and forms conjugates with other
      molecules via its sulfhydryl moiety. The interactions of the common heavy metal
      pollutant Cd(II) with GSH were determined by using the Brdicka reaction to
      evaluate whether this technique would be suitable as a biomarker. After GSH
      interaction with Cd(II) ions, two characteristic changes in the measured
      voltammogram were observed: Cat2 signal height decreased, and a new signal called
      P1 was found. The observed signal probably relates to the formation of a GSH
      heavy metal ion complex adsorbed on the surface of the working electrode. When
      the interaction of GSH with cisplatin was studied, the same characteristic
      changes in the voltammogram were observed, which confirmed our hypothesis.
      Moreover, changes in the height of P1 and Cat2 signals with increasing time of
      GSH interaction with Cd(II) ions and/or cisplatin were also investigated. Cat2
      peak height decreased proportionally with increasing time of interaction. This
      decrease can be explained by shielding of free sulfhydryl moiety by heavy metal
      ions, so it cannot catalyze the evolution of hydrogen from the supporting
      electrolyte. In addition, we found that, with increasing time of the interaction,
      the P1 signal was enhanced and shifted to more positive potentials for both
      Cd(II) ions and cisplatin.

PMID- 20821471
TI  - Heavy metals and metallothionein in vespertilionid bats foraging over aquatic
      habitats in the Czech Republic.
AB  - There has been growing interest in the study and conservation of bats throughout
      the world. Declines in their absolute numbers in recent decades are due, in part,
      to the fact that insectivorous bats may bioaccumulate toxic pollutants. The
      purpose of the present study was to quantify heavy metal concentrations in
      kidney, liver, and pectoral muscle samples in relation to metallothionein (MT)
      levels. In total, 106 bats belonging to 11 European species (i.e., Myotis myotis,
      Myotis daubentonii, Myotis brandtii, Myotis nattereri, Myotis emarginatus, Myotis
      mystacinus, Pipistrellus pipistrellus, Pipistrellus nathusii, Pipistrellus
      pygmaeus, Nyctalus noctulla, Eptesicus serotinus) were used for the study. The
      highest MT levels were found in Pipistrellus pipistrellus. High MT levels were
      also found in juvenile bats and aquatic-insect-foraging species. Cadmium was
      found only in the liver and kidney of Myotis myotis, except for a solitary
      finding in Pipistrellus pipistrellus. Myotis myotis juveniles had significantly
      higher liver and kidney Zn concentrations than adults. Interestingly, the liver
      Pb concentration was approximately two times higher in females than in males of
      Myotis myotis. The same gender difference was found for kidney Zn concentration
      in Pipistrellus pipistrellus. The present study confirms exposure of
      vespertilionid bats to toxic heavy metals (Pb, Cd) in the Czech Republic and
      provides data on the essential element Zn and the metal-binding protein MT in
      bats foraging over aquatic, aquatic and terrestrial, and terrestrial habitats.

PMID- 20821472
TI  - Kinetic bacterial bioluminescence assay for contact sediment toxicity testing:
      relationships with the matrix composition and contamination.
AB  - The present study represents the first broader evaluation of the rapid 30-s
      kinetic bioluminescence assay with Vibrio fisheri (microplate format
      modification) for contact toxicity testing of whole sediments. The present study
      focused on river sediments from the Morava River basin, Czech Republic,
      repeatedly sampled during 2005 to 2006 and analyzed for geological and
      geochemical parameters, content of toxic metals, major organic pollutants, and
      toxicity. High natural variation in toxicity (50% inhibitory concentration [IC50]
      values ranging from 0.8 to >80 mg sediment dry wt/ml) was found (among different
      sampling periods and years, among sites), and this could be related to the
      sediment dynamics affected by spring high flows and summer droughts. From the 46
      sediment descriptors, exchangeable protons (H(+)) was the only parameter that
      consistently correlated with toxicity. Three other descriptors (i.e., content of
      organic carbon plus two parameters from the detailed silicate analysis of
      sediments: percentage of SO(3) representing total sulfur content, structural
      water H(2)O+) also significantly correlated with toxicity. There were only minor
      and variable correlations with contamination. We propose sediment safety
      guideline categories for the V. fisheri kinetic test with severe toxicity
      threshold of IC50 < 1 mg dry wt/ml. Although sediments are considered a rather
      stable matrix in comparison with river water, we confirmed high variability and
      dynamics that should be reflected in monitoring plans and field studies.

PMID- 20821473
TI  - Liver, gills, and skin histopathology and heavy metal content of the Danube
      sterlet (Acipenser ruthenus Linnaeus, 1758).
AB  - The sterlet (Acipenser ruthenus L.) is a bottom-feeding fish species with a
      direct exposure to contaminants from water and sediments. Although heavy metal
      pollution is believed to be one of the main threats to the sterlet population in
      the Danube River basin, there is a lack of knowledge of the exact impact of heavy
      metals on their survival. In the present study, effects of heavy metal pollution
      on sterlet in the Danube basin were assessed as well as the utility of different
      sterlet organs and tissues as indicators of heavy metal contamination. The
      sterlet were sampled at three different sites in the Danube basin, in Hungary and
      Serbia, isolated from each other by dams. Heavy metal analysis included
      measurement of Cd, As, Pb, Cr, Hg, Cu, Ni, Fe, Mn, and Zn concentrations in
      sterlet gills, muscle, liver, and intestine, and histopathological analyses
      comprised assessment and scoring of the extent and intensity of alterations in
      skin, gills, and liver tissue. Analysis revealed a significant presence of
      sublethal histopathological changes that were most pronounced in the liver and
      skin and increased accumulation of heavy metals, with the highest concentrations
      in the liver. Canonical discriminant analysis showed significant differentiation
      among the three studied localities, suggesting that the heavy metal
      concentrations in sterlet populations were site specific. The present study
      concludes that the accumulation of heavy metals is a response to the presence of
      these pollutants in the environment, and, together with other pollutants, it
      affects the vital organs of natural sterlet populations.

PMID- 20821474
TI  - Seasonally and regionally determined indication potential of bioassays in
      contaminated river sediments.
AB  - River sediments are a dynamic system, especially in areas where floods occur
      frequently. In the present study, an integrative approach is used to investigate
      the seasonal and spatial dynamics of contamination of sediments from a regularly
      flooded industrial area in the Czech Republic, which presents a suitable model
      ecosystem for pollutant distribution research at a regional level. Surface
      sediments were sampled repeatedly to represent two different hydrological
      situations: spring (after the peak of high flow) and autumn (after longer period
      of low flow). Samples were characterized for abiotic parameters and
      concentrations of priority organic pollutants. Toxicity was assessed by Microtox
      test; genotoxicity by SOS-chromotest and green fluorescent protein (GFP)-yeast
      test; and the presence of compounds with specific mode of action by in vitro
      bioassays for dioxin-like activity, anti-/androgenicity, and anti-/estrogenicity.
      Distribution of organic contaminants varied among regions and seasonally.
      Although the results of Microtox and genotoxicity tests were relatively
      inconclusive, all other specific bioassays led to statistically significant
      regional and seasonal differences in profiles and allowed clear separation of
      upstream and downstream regions. The outcomes of these bioassays indicated an
      association with concentrations of polycyclic aromatic hydrocarbons (PAHs) and
      polychlorinated biphenyls (PCBs) as master variables. There were significant
      interrelations among dioxin-like activity, antiandrogenicity and content of
      organic carbon, clay, and concentration of PAHs and PCBs, which documents the
      significance of abiotic factors in accumulation of pollutants. The study
      demonstrates the strength of the specific bioassays in indicating the changes in
      contamination and emphasizes the crucial role of a well-designed sampling plan,
      in which both spatial and temporal dynamics should be taken into account, for the
      correct interpretations of information in risk assessments.

PMID- 20821475
TI  - Effect of nitrite on early-life stages of common carp (Cyprinus carpio L.).
AB  - A one-month chronic exposure of common carp larvae and embryos to nitrite
      revealed significant (p < 0.01) differences in total accumulated mortality in
      fish exposed to 33, 67, and 330 mg/L NO(2)(-) compared with controls. At the
      highest concentration, all fish died within 8 d of exposure. On the basis of
      accumulated mortality in the experimental groups, lethal concentrations of
      nitrite were estimated at 29 d LC50 = 88 mg/L NO(2)(-); lowest-observed-effect
      concentration (LOEC) = 28 mg/L NO(2)(-); and no-observed-effect concentration
      (NOEC) = 7 mg/L NO(2)(-). Fulton's condition factor values were significantly
      lower in fish from all experimental groups compared with controls. By day 12,
      fish exposed to 33 and 67 mg/L NO(2)(-) had significantly lower mass and total
      length compared with controls. No significant negative effects of nitrite at the
      concentrations tested (0.7-330 mg/L NO(2)(-), at 10 mg/L Cl(-)) on hatching or
      embryo viability were demonstrated, but significant differences in early ontogeny
      among groups were noted. Fish from all the concentrations showed a dose-related
      delay in development compared with the controls. Lordosis, kyphosis, scoliosis,
      and body shortening were observed at all concentrations and in controls, as was
      yolk sac deformation and edema, eye deformation, and cardiac edema. The incidence
      of these malformations was positively correlated with nitrite concentration.
      Histopathology revealed epidermal spongiosis; edema and hyperplasia of the gill
      epithelium, including hypertrophy and hyperplasia of eosinophilic granular cells
      (chloride cells); and interstitial edema of skeletal muscle in fish exposed to 67
      mg/L NO(2)(-). Similar, but milder, changes were observed at lower nitrite
      concentrations.

PMID- 20821476
TI  - Assessment of contamination of the Svitava and Svratka rivers in the Czech
      Republic using selected biochemical markers.
AB  - The aim of the present study is to assess aquatic ecosystem contamination using
      selected biochemical markers: cytochrome P450, ethoxyresorufin-O-deethylase
      (EROD), glutathione S-transferase (GST), tripeptide glutathione, vitellogenin,
      and 11-ketotestosterone in chub (Leuciscus cephalus L.). Seven locations on the
      Svitava and Svratka rivers (in the Brno conurbation, Czech Republic) were
      assessed. The results were compared with the levels of the most important
      inductors of these biomarkers: organic pollutants hexachlorocyclohexane (HCH),
      hexachlorobenzene (HCB), DDT and its metabolites, polychlorinated biphenyls, and
      polycyclic aromatic hydrocarbons in bottom sediment, fish muscle, and
      semipermeable membrane devices (SPMDs) and metals in sediment. The highest levels
      of pollutants were observed at sites situated downstream from Brno, especially at
      Modrice and Rajhradice. Significant positive correlations (p < 0.05) were found
      between EROD activity and HCH concentration in SPMDs, and also between GST and
      EROD activity with HCB concentration in muscle, after adjusting for age.

PMID- 20821477
TI  - Passive sampling methods for monitoring endocrine disruptors in the Svratka and
      Svitava rivers in the Czech Republic.
AB  - Endocrine-disrupting chemicals (EDC) are manmade or natural chemicals that have
      the ability to interfere with the endocrine system of animals. They have not been
      monitored systematically in the Czech Republic. The goal of the present study was
      the characterization of aquatic environmental pollution from the Brno (Czech
      Republic) city agglomeration focusing on EDC. Passive sampling devices, as well
      as semipermeable membrane devices (SPMD) and polar organic chemical integrative
      samplers (POCIS), were used for the pilot assessment of EDC. They were deployed
      for 21- to 28-d periods at nine locations in the Svratka and Svitava Rivers,
      Brno, Czech Republic, including at the inlet and outlet of Brno's wastewater
      treatment plant. The SPMDs were used to monitor nonpolar compounds such as
      polychlorinated biphenyls (PCBs), polynuclear aromatic hydrocarbons (PAHs), and
      organochlorinated pesticides (OCP). The POCIS were used to monitor polar
      compounds such as pesticides and their metabolites, perfluoro-organic compounds
      (PFOC), and pharmaceuticals. The passive samplers allowed very low detection
      limits for soluble (bioavailable) fractions of pollutants. The contribution of
      PAH, PCB, and HCB in sewage water to pollution of the Svratka River was low. The
      Brno wastewater treatment plant was identified as the main source of
      pharmaceuticals, triclosan, methyl triclosan, and some polar pesticides.

PMID- 20821478
TI  - Toxicity of cyanobacterial bloom in the eutrophic dam reservoir (Southeast
      Poland).
AB  - Cyanobacterial bloom was observed in a highly eutrophic dam reservoir,
      Zemborzycki, near Lublin (SE Poland) over a warm period in the year 2007. The
      water bloom consisted of several cyanobacterial taxa: Anabaena circinalis,
      Anabaena spiroides, Anabaena flos-aquae, Planktothrix agardhii, Aphanizomenon
      flos-aquae, Aphanizomenon gracile, and Microcystis flos-aquae. Anabaena spp., and
      Aphanizomenon spp., potential producers of neurotoxic anatoxin-a, quantitatively
      predominated in the studied bloom. High-performance liquid chromatography (HPLC)
      analysis of surface scum sampled during Anabaena circinalis domination revealed
      the presence of anatoxin-a at a high concentration (1,035.59 microg per liter of
      surface scum). At the same time, neither gas chromatography/mass spectrometry
      (GC/MS) nor microcystin enzyme-linked immunosorbent assay (ELISA) test showed the
      presence of other frequently found cyanotoxins, microcystins. Toxicity of
      cyanobacterial bloom was assessed by the crustacean acute toxicity test
      Daphtoxkit F pulex using Daphnia pulex, and by the chronic toxicity test
      Protoxkit F with a ciliate protozoan Tetrahymena thermophila. The crude extract
      of cyanobacterial scum showed high toxicity for Daphnia pulex, with 24-h median
      effective concentration (EC50) value of 90.3 microg/L of anatoxin-a, which
      corresponded to the cyanobacterial density in the scum of 1.01 g dry weight/L.
      For Tetrahymena thermophila, 24-h EC50 was lower, evaluated to be 60.48 microg/L
      of anatoxin-a, which corresponded to a cyanobacterial density of 0.68 g dry
      weight/L of the scum. On the basis of evaluated toxicity units, the
      cyanobacterial extract was classified at class IV toxicity, which means high
      toxic hazard.

PMID- 20821479
TI  - Impact of microcystin containing diets on physiological performance of Nile
      tilapia (Oreochromis niloticus) concerning stress and growth.
AB  - Diets containing Microcystis with considerable amounts of the cyanotoxin
      microcystin-LR (MC-LR) were fed to determine their impact on the physiological
      performance of the omnivorous Nile tilapia (Oreochromis niloticus) with regard to
      stress and growth performance. Four different diets were prepared based on a
      commercial diet (control, MC-5% [containing 5% dried Microcystis biomass], MC-20%
      [containing 20% dried Microcystis biomass], and Arthrospira-20% [containing 20%
      dried Arthrospira sp. biomass without toxin]) and fed to female Nile tilapia.
      Blood and tissue samples were taken after 1, 7, and 28 d, and MC-LR was
      quantified in gills, muscle, and liver by using high-performance liquid
      chromatography (HPLC). Only in the liver were moderate concentrations of MC-LR
      detected. The stress hormone cortisol and glucose were analyzed from plasma,
      suggesting that all modified diets caused only minor to moderate stress, which
      was confirmed by analyses of hepatic glycogen. In addition, the effects of the
      different diets on growth performance were investigated by determining gene
      expression of hypophyseal growth hormone (GH) and hepatic insulin-like growth
      factor-I (IGF-I). For all diets, quantitative reverse transcription-polymerase
      chain reaction (RT-qPCR) demonstrated no significant effect on gene expression of
      the major endocrine hormones of the growth axis, whereas classical growth data,
      including growth and feed conversion ratio, displayed slight inhibitory effects
      of all modified diets independent of their MC-LR content. However, no significant
      change was found in condition or hepatosomatic index among the various diets, so
      it seems feasible that dried cyanobacterial biomass might be even used as a
      component in fish diet for Nile tilapia, which requires further research in more
      detail.

PMID- 20821480
TI  - Microcystin-LR modulates selected immune parameters and induces
      necrosis/apoptosis of carp leucocytes.
AB  - Microcystins (MCs) are potent hepatotoxins acting by the inhibition of protein
      phosphatase 1 and 2A, and may promote liver tumors. Moreover, studies also
      suggest they are nephrotoxic. The aim of the present study was to assess possible
      in vitro effects of microcystin-LR (which contains the amino acids leucine and
      arginine, the most widely studied and distributed variant of all microcystins) on
      the selected immune functions of the cells isolated from the head kidney of carp.
      In the experiments, pure microcystin-LR (MC-LR), was used at concentrations of
      0.01, 0.1, 0.5, and 1 microg/ml RPMI-1640 medium. Leucocytes (lymphocytes and
      phagocytes) were isolated by centrifugation on a density gradient. Lymphocyte
      proliferation, intracellular production of reactive oxygen species by phagocytes,
      and the presence of apoptotic and/or necrotic cells were assessed. The
      respiratory burst activity of phagocytic cells was increased at the lowest toxin
      concentration used in the study, but it was decreased at higher concentrations.
      Using a sensitive luminescent immunoassay, MC-LR was observed to have no
      influence on the T-cell proliferation but decreased the proliferation of B
      lymphocytes. Moreover, it was noted that MC-LR induced necrosis to a higher
      degree than apoptosis in fish leucocytes. The results of the present study
      suggest the modulatory potency of microcystin-LR on fish leucocytes.

PMID- 20821481
TI  - The role of indirect photolysis in limiting the persistence of crop protection
      products in surface waters.
AB  - The photodegradation of six crop protection products (CPPs) was studied in 16
      natural waters collected from across the midwest of the United States under
      simulated sunlight to determine the significance of indirect photolysis. The rate
      of degradation of five of the CPPs was faster in irradiated natural waters than
      in buffer systems, with the effect particularly significant with the relatively
      photostable compounds propiconazole and prometryn. Degradation rates were
      correlated with the concentration of one or more photosensitizers, or ratios
      thereof, by means of a Pearson's correlation and linear regression analysis. It
      was found that the photodegradation of chlorotoluron, pinoxaden, propiconazole
      and prometryn were linked to the concentration of nitrate, pointing to a
      significant role of hydroxyl radical ((.)OH) as a reactive intermediate.
      Increased concentrations of dissolved organic carbon (DOC) and bicarbonate
      relative to nitrate were found to decrease the rate of degradation of these
      compounds, consistent with a quenching role. Chlorothalonil appeared to be
      rapidly degraded by means of the carbonate radical ((.)CO(3)(-)), whereas the
      photodegradation of emamectin was particularly complex. Overall, indirect
      photolysis significantly enhanced the rate of CPP degradation and fate models
      based on these experiments appear to offer more realism than those that only take
      into account direct photolysis.

PMID- 20821482
TI  - Enhanced migration of polychlorodibenzo-p-dioxins and furans in the presence of
      pentachlorophenol-treated oil in soil around utility poles: screening model
      validation.
AB  - Field samples were collected around six pentachlorophenol (PCP)-treated wooden
      poles (in clay, organic soil, and sand) to evaluate the vertical migration of
      polychlorodibenzo-p-dioxins and furans (PCDD/Fs). Soils were characterized,
      PCDD/Fs, C(10)-C(50), and PCP were analyzed for seven composite samples located
      at a depth from 0 to 100 cm and at a distance from 0 to 50 cm from each pole.
      Concentrations of PCDD/Fs measured in organic soils were the highest (maximum
      1.2E + 05 pg toxic equivalent TEQ/g soil), followed by clay (maximum 3.8E + 04 pg
      TEQ/g soil) and sand (maximum 1.8E + 04 pg TEQ/g soil). Model predictions,
      including the influence of wood treatment oil, were validated using measured
      concentration values in soils around poles. The model predicts a migration of
      PCDD/Fs due to the migration of oil, which differs depending on the type of soil:
      in clay, 90% of PCDD/Fs are predicted to remain in the first 29 cm, whereas in
      sand, 80 to 90% of the emitted PCDD/Fs are predicted to migrate deeper than 185
      cm. For the organic soil, the predicted migration depth varies from 90 to 155 cm.
      This screening model allows evaluating the danger of microcontaminated sites
      around PCP-treated wooden poles: from a risk assessment perspective, in the case
      of organic soil and clay, no PCDD/F contamination is to be expected below the
      pole, but high levels of PCDD/Fs can be found in the first 2 m below the surface.
      For sand, however, significantly lower levels of PCDD/Fs were predicted in the
      surface soil, while the migration depth remains elevated, posing an inherent
      danger of aquifer contamination under the pole.

PMID- 20821483
TI  - Modeling the response of passive samplers to varying ambient fluid concentrations
      of organic contaminants.
AB  - Passive samplers are an important and versatile adjunct to active sampling
      methods for air and water. The underlying theory is increasingly mature but is
      often based on the assumption of constant concentrations with time in the ambient
      fluid. This theoretical work details the passive sampler response to possible
      environmental situations in which ambient concentrations vary linearly with time,
      decrease exponentially with time, constitute a pulsed event, or oscillate
      regularly with time. The modeled shape of sampler response curve with time is
      characteristic and can be used to determine how fluid concentrations have changed
      with time. The sampler elimination rate constant is shown to be crucial in
      governing sampler response. Thus, by using performance reference compounds and
      under certain conditions, information from the sampler response can in theory be
      used to derive specific details of the temporal variation of the contaminant in
      the ambient fluid. For example, data captured by a passive sampler can be used to
      characterize a contamination pulse. This extends the versatility of passive
      samplers.

PMID- 20821484
TI  - Triclocarban, triclosan, polybrominated diphenyl ethers, and 4-nonylphenol in
      biosolids and in soil receiving 33-year biosolids application.
AB  - Land application of biosolids is a common practice throughout the world. However,
      concerns continue to be raised about the safety of this practice, because
      biosolids may contain trace levels of organic contaminants. The present study
      evaluated the levels of triclocarban (TCC), triclosan (TCS), 4-nonylphenol (4
      NP), and polybrominated diphenyl ethers (PBDEs) in biosolids from 16 wastewater
      treatment plants and in soils from field plots receiving annual applications of
      biosolids for 33 years. All of the four contaminants evaluated were detected in
      most of the biosolids at concentrations ranging from hundreds of microg/kg to
      over 1,000 mg/kg (dry wt basis). They were detected at microg/kg levels in the
      biosolids-amended soil, but their concentrations decreased sharply with
      increasing soil depth for 4-NP, PBDEs, and TCC, indicating limited soil leaching
      of those compounds. However, potential leaching of TCS in the biosolids-amended
      soils was observed. The levels of all four compounds in the surface soil
      increased with increasing biosolids application rate. Compared with the estimated
      33-year cumulative input to the soil during the 33-year consecutive biosolids
      application, most of the PBDEs and a small percentage of 4-NP, TCC, and TCS
      remained in the top 120-cm soil layer. These observations suggest slow
      degradation of PBDEs but rapid transformation of 4-NP, TCC, and TCS in the
      biosolids-amended soils.

PMID- 20821485
TI  - Selenium distribution in a lake system receiving effluent from a metal mining and
      milling operation in Northern Saskatchewan, Canada.
AB  - The release of selenium (Se) at relatively low concentrations into aquatic
      ecosystems over time can result in the accumulation and, if thresholds are
      exceeded, subsequent adverse effects in sensitive species, including higher
      trophic levels (such as fish). A milling operation in Northern Saskatchewan,
      Canada, releases treated effluent into a small stream system, and Se has
      accumulated in sediments and aquatic biota over time. The present study evaluated
      four small lakes downstream of the effluent discharge point, and one lake
      upstream, in order to describe and understand the distribution of Se in abiotic
      environmental compartments and the transfer of Se into benthic
      macroinvertebrates. The concentrations of Se in sampled sediments were highly
      variable but exceeded proposed thresholds for the protection of fish and aquatic
      birds in all study lakes downstream of the effluent discharge point. Selenium
      concentrations in surface water, whole-sediment, and sediment pore water revealed
      that whole-body Se concentrations in benthic invertebrates (chironomids) are best
      correlated with Se in pore water. It is proposed that Se accumulates in sediments
      through an association with the total organic carbon content of sediment and that
      Se is fixed from the surface water by micro-organisms and primary producers. The
      relationship between Se in pore water and Se in whole sediments appears to be
      influenced by the organic carbon content of each medium, and Se bioavailability
      in sediment and transfer to higher trophic levels via benthic macroinvertebrates
      is likely speciation dependent.

PMID- 20821486
TI  - Evaluation of hexavalent chromium in sediment pore water of the Hackensack River,
      New Jersey, USA.
AB  - Pore water was collected from in situ passive samplers in Hackensack River
      sediments adjacent to a chromite ore processing residue site in Kearny, New
      Jersey. Although the sediments at this site contained more than 3,000 mg/kg of
      total chromium (Cr) and shallow groundwater adjacent to the shore contained more
      than 1,000 microg/L of hexavalent Cr [Cr(VI)], concentrations of dissolved total
      Cr and Cr(VI) in pore water (PW) samples were less than ambient water quality
      criteria for Cr(VI) (50 microg/L). Concentrations of dissolved total Cr in pore
      water ranged from <2.0 to 5.3 microg/L, while Cr(VI) was not detected (<10
      microg/L). These findings are consistent with previous studies, which
      demonstrated limited bioavailability and toxicity of Cr in sediment at this site
      and others with similar conditions.

PMID- 20821487
TI  - Mercury concentrations in landlocked Arctic char (Salvelinus alpinus) from the
      Canadian Arctic. Part I: insights from trophic relationships in 18 lakes.
AB  - Concentrations of mercury (Hg) have increased slowly in landlocked Arctic char
      over a 10- to 15-year period in the Arctic. Fluxes of Hg to sediments also show
      increases in most Arctic lakes. Correlation of Hg with trophic level (TL) was
      used to investigate and compare biomagnification of Hg in food webs from lakes in
      the Canadian Arctic sampled from 2002 to 2007. Concentrations of Hg (total Hg and
      methylmercury [MeHg]) in food webs were compared across longitudinal and
      latitudinal gradients in relation to delta(13)C and delta(15)N in periphyton,
      zooplankton, benthic invertebrates, and Arctic char of varying size-classes.
      Trophic magnification factors (TMFs) were calculated for the food web in each
      lake and related to available physical and chemical characteristics of the lakes.
      The relative content of MeHg increased with trophic level from 4.3 to 12.2% in
      periphyton, 41 to 79% in zooplankton, 59 to 72% in insects, and 74 to 100% in
      juvenile and adult char. The delta(13)C signatures of adult char indicated
      coupling with benthic invertebrates. Cannibalism among char lengthened the food
      chain. Biomagnification was confirmed in all 18 lakes, with TMFs ranging from 3.5
      +/- 1.1 to 64.3 +/- 0.8. Results indicate that TMFs and food chain length (FCL)
      are key factors in explaining interlake variability in biomagnification of [Hg]
      among different lakes.

PMID- 20821488
TI  - Mercury concentrations in landlocked Arctic char (Salvelinus alpinus) from the
      Canadian Arctic. Part II: influence of lake biotic and abiotic characteristics on
      geographic trends in 27 populations.
AB  - Among-lake variation in mercury (Hg) concentrations in landlocked Arctic char was
      examined in 27 char populations from remote lakes across the Canadian Arctic. A
      total of 520 landlocked Arctic char were collected from 27 lakes, as well as
      sediments and surface water from a subset of lakes in 1999, 2002, and 2005 to
      2007. Size, length, age, and trophic position (delta(15)N) of individual char
      were determined and relationships with total Hg (THg) concentrations
      investigated, to identify a common covariate for adjustment using analysis of
      covariance (ANCOVA). A subset of 216 char from 24 populations was used for
      spatial comparison, after length-adjustment. The influence of trophic position
      and food web length and abiotic characteristics such as location, geomorphology,
      lake area, catchment area, catchment-to-lake area ratio of the lakes on adjusted
      THg concentrations in char muscle tissue were then evaluated. Arctic char from
      Amituk Lake (Cornwallis Island) had the highest Hg concentrations (1.31 microg/g
      wet wt), while Tessisoak Lake (Labrador, 0.07 microg/g wet wt) had the lowest.
      Concentrations of THg were positively correlated with size, delta(15)N, and age,
      respectively, in 88, 71, and 58% of 24 char populations. Length and delta(15)N
      were correlated in 67% of 24 char populations. Food chain length did not explain
      the differences in length-adjusted THg concentrations in char. No relationships
      between adjusted THg concentrations in char and latitude or longitude were found,
      however, THg concentrations in char showed a positive correlation with catchment
      to-lake area ratio. Furthermore, we conclude that inputs from the surrounding
      environment may influence THg concentrations, and will ultimately affect THg
      concentrations in char as a result of predicted climate-driven changes that may
      occur in Arctic lake watersheds.

PMID- 20821489
TI  - Effects of sublethal concentrations of bifenthrin and deltamethrin on fecundity,
      growth, and development of the honeybee Apis mellifera ligustica.
AB  - Bifenthrin and deltamethrin have been widely used as pesticides in agriculture
      and forestry and are becoming an increasing risk to honeybees. The honeybee, Apis
      mellifera ligustica, is widely recognized as a beneficial insect of agronomic,
      ecological, and scientific importance. It is important to understand what effects
      these chemicals have on bees. Effects of two pesticides at sublethal
      concentrations on fecundity, growth, and development of honeybees were examined
      with the feeding method for a three-year period (2006-2008). It was shown that
      both bifenthrin and deltamethrin significantly reduced bee fecundity, decreased
      the rate at which bees develop to adulthood, and increased their immature
      periods. The toxicity of bifenthrin and deltamethrin on workers of Apis mellifera
      ligustica was also assessed, and the results from the present study showed that
      the median lethal effects of bifenthrin and deltamethrin were 16.7 and 62.8 mg/L,
      respectively.

PMID- 20821490
TI  - Enhanced reproduction in mallards fed a low level of methylmercury: an apparent
      case of hormesis.
AB  - Breeding pairs of mallards (Anas platyrhynchos) were fed a control diet or a diet
      containing 0.5 microg/g mercury (Hg) in the form of methylmercury chloride. There
      were no effects of Hg on adult weights and no overt signs of Hg poisoning in
      adults. The Hg-containing diet had no effect on fertility of eggs, but hatching
      success of eggs was significantly higher for females fed 0.5 microg/g Hg (71.8%)
      than for controls (57.5%). Survival of ducklings through 6 d of age was the same
      (97.8%) for controls and mallards fed 0.5 microg/g mercury. However, the mean
      number of ducklings produced per female was significantly higher for the pairs
      fed 0.5 microg/g Hg (21.4) than for controls (16.8). Although mercury in the
      parents' diet had no effect on mean duckling weights at hatching, ducklings from
      parents fed 0.5 microg/g Hg weighed significantly more (mean = 87.2 g) at 6 d of
      age than did control ducklings (81.0 g). The mean concentration of Hg in eggs
      laid by parents fed 0.5 microg/g mercury was 0.81 microg/g on a wet-weight basis.
      At this time, one cannot rule out the possibility that low concentrations of Hg
      in eggs may be beneficial, and this possibility should be considered when setting
      regulatory thresholds for methylmercury.

PMID- 20821491
TI  - Effects of mercury on reproduction, avoidance, and heat shock protein gene
      expression of the soil springtail Folsomia candida.
AB  - Based on the Cambisols of Beijing (used as agricultural soils), toxicity tests
      were conducted to investigate the effects of mercury (Hg) on reproduction and
      avoidance of Folsomia candida (Hexapoda: Collembola), as well as the
      transcriptional responses of the hsp70 gene, under different Hg concentrations
      and at different exposure times. Results showed that the hsp70 gene of the
      springtail was the most sensitive parameter to soil Hg stress, with a half
      maximal effective concentration (EC50) of 0.42 mg/kg. The EC50 values based on
      reproduction and avoidance tests were 9.29 and 3.88 mg/kg, respectively. The
      expression level of the hsp70 gene was significantly up-regulated when soil Hg
      concentration was over 0.25 mg/kg (lowest-observed-effect concentration [LOEC]).
      In addition, responses of this gene expression were strongly induced after 48 h
      exposure under 1 mg/kg soil Hg, which probably was due to the fast and sensitive
      response of the gene transcription to Hg stress. Thus, the results suggested that
      the responses of the hsp70 gene and individual-level effects (reproduction and
      avoidance) could be integrated to provide helpful information for environmental
      monitoring and assessment of contaminated soils.

PMID- 20821492
TI  - Molecular docking and comparative molecular similarity indices analysis of
      estrogenicity of polybrominated diphenyl ethers and their analogues.
AB  - Molecular docking and three-dimensional quantitative structure-activity
      relationships (3D-QSAR) were used to develop models to predict estrogenicity of
      polybrominated diphenyl ethers (PBDEs), para-hydroxylated polybrominated diphenyl
      ethers (para-HO-PBDEs), and brominated bisphenol A compounds to the human
      estrogen receptor alpha (hERalpha). Based on the molecular conformations
      developed from the molecular docking, predictive comparative molecular similarity
      indices analysis (CoMSIA) models were developed. The results of CoMSIA modeling
      with region focusing included were: leave-one-out (LOO) cross-validated
      coefficient q(2)(LOO) = 0.722 (all 26 compounds), q(2)(LOO) = 0.633 (the training
      set, 20 compounds), q(2)(LMO, two groups) = 0.520 +/- 0.155 (26 compounds),
      q(2)(LMO, five groups) = 0.665 +/- 0.068 (26 compounds), predictive r(2),
      r(2)(pred) = 0.686 (the test set, 6 compounds), and Q(2)(EXT) = 0.678. The 3D
      QSAR can be used to infer the activities of compounds with similar structural
      characteristics. The interaction mechanism between compounds and the hERalpha was
      explored. Hydrogen bonding of the compound with Glu353 in the hERalpha is an
      important determinant of the estrogenic activity of para-HO-PBDEs and brominated
      bisphenol A.

PMID- 20821493
TI  - Developmental phytotoxicity of metal oxide nanoparticles to Arabidopsis thaliana.
AB  - Phytotoxicity is an important consideration to understand the potential
      environmental impacts of manufactured nanomaterials. Here, we report on the
      effects of four metal oxide nanoparticles, aluminum oxide (nAl(2)O(3)), silicon
      dioxide (nSiO(2)), magnetite (nFe(3)O(4)), and zinc oxide (nZnO), on the
      development of Arabidopsis thaliana (Mouse-ear cress). Three toxicity indicators
      (seed germination, root elongation, and number of leaves) were quantified
      following exposure to each nanoparticle at three concentrations: 400, 2,000, and
      4,000 mg/L. Among these particles, nZnO was most phytotoxic, followed by
      nFe(3)O(4), nSiO(2), and nAl(2)O(3), which was not toxic. Consequently, nZnO was
      further studied to discern the importance of particle size and zinc dissolution
      as toxicity determinants. Soluble zinc concentrations in nanoparticle suspensions
      were 33-fold lower than the minimum inhibitory concentration of dissolved zinc
      salt (ZnCl(2)), indicating that zinc dissolution could not solely account for the
      observed toxicity. Inhibition of seed germination by ZnO depended on particle
      size, with nanoparticles exerting higher toxicity than larger (micron-sized)
      particles at equivalent concentrations. Overall, this study shows that direct
      exposure to nanoparticles significantly contributed to phytotoxicity and
      underscores the need for eco-responsible disposal of wastes and sludge containing
      metal oxide nanoparticles.

PMID- 20821494
TI  - Polluted-site killifish (Fundulus heteroclitus) embryos are resistant to organic
      pollutant-mediated induction of CYP1A activity, reactive oxygen species, and
      heart deformities.
AB  - Exposure to coplanar polychlorinated biphenyls (PCBs) and polycyclic aromatic
      hydrocarbons (PAHs) can adversely affect fish embryonic development, induce
      expression of cytochrome P4501A (CYP1A), and increase reactive oxygen species
      (ROS) production, effects believed to be mediated by the aryl hydrocarbon
      receptor (AHR). Killifish (Fundulus heteroclitus) populations in New Bedford
      Harbor, Massachusetts, USA (NBH) and Newark Bay, New Jersey, USA (NB) are
      generationally exposed to coplanar PCBs and PAHs and have developed resistance to
      PCB mediated induction of CYP1A. We hypothesized that fish resistant to CYP1A
      induction would also exhibit resistance to PCB and PAH induced ROS production and
      teratogenesis. Killifish embryos from two contaminated (NB, NBH) and two
      reference-site populations were exposed to vehicle or 3,3'4,4'5
      pentachlorobiphenyl (PCB126) or 3-methylcholanthrene (3-MC) and evaluated for in
      ovo CYP1A activity, heart deformities, and ROS production. Both chemicals
      significantly increased in ovo ethoxyresorufin-O-deethylase (EROD) and ROS
      production in reference-site embryos. These chemicals provoked only moderate
      induction of in ovo EROD in NBH and NB embryos, and neither PCB126 nor 3-MC
      induced ROS production in these populations. Similarly, heart deformities were
      significantly induced by PCB126 in reference-site embryos, but had no significant
      effects on NB and NBH animals. These results indicate that fish resistant to
      CYP1A induction also exhibit decreased sensitivity to PCB126 and 3-MC-induced ROS
      production and teratogenesis. These findings further our understanding of
      toxicant resistance by demonstrating that reduced response to coplanar PCBs and
      PAHs extends beyond resistance to CYP1A induction to resistance to the
      physiological and teratogenic effects of these toxicants, responses that
      undoubtedly contribute to the increased survival of killifish inhabiting
      contaminated sites.

PMID- 20821495
TI  - Enantioselective induction of oxidative stress by permethrin in rat adrenal
      pheochromocytoma (PC12) cells.
AB  - Synthetic pyrethroid (SP) insecticides are chiral compounds with multiple
      asymmetric positions. Several recent studies have focused on the effect of
      enantioselectivity of SPs in acute aquatic toxicity, endocrine-disrupting
      activities, and immunotoxicity. However, the relevant molecular mechanisms are
      still unknown. The potential relationship between ecotoxicological effects and
      oxidative stress could contribute to SP-induced enantioselective cytotoxicity,
      but this requires further investigation. Therefore, this study was undertaken to
      evaluate the role of oxidative stress in enantiomer-specific permethrin (PM)
      induced cytotoxicity in rat adrenal pheochromocytoma (PC12) cells. The study
      demonstrated that PM induced enantioselective oxidative stress and cytotoxicity.
      The reactive oxygen species (ROS) generation and lipid peroxidation production of
      malondialdehyde (MDA) were obviously increased, whereas the activity of
      antioxidant enzymes (superoxide dismutase [SOD] and catalase [CAT]) and
      glutathione (GSH) content had declined after exposure in 1R-trans-PM at a
      concentration of 30 mg/L. Meanwhile, the result of the cytotoxicity assay showed
      a clear, dose-dependent growth-inhibition effect of PM in an enantioselective
      manner. The most toxic effect on PC12 cells was shown by 1R-trans-PM and was
      approximately 1.6 times higher than that with 1S-cis-PM, which exhibited only a
      slightly toxic effect at a concentration of 20 mg/L. These results suggested that
      PM exhibited significant enantioselectivity in oxidative stress, which may be one
      of the initial events in PM-induced enantioselective cytotoxicity. The present
      study also improved understanding of enantiomer-specific, SP-induced
      cytotoxicity. The enantioselectivity should be taken into consideration when
      assessing ecological effects and development of new chiral pesticides.

PMID- 20821496
TI  - Thermal tolerance of juvenile freshwater mussels (Unionidae) under the added
      stress of copper.
AB  - Freshwater mussels fulfill an essential role in aquatic communities, but are also
      one of the most sensitive and rapidly declining faunal groups in North America.
      Rising water temperatures, caused by global climate change or industrial
      discharges, can further challenge impaired unionid communities, but thermal
      stress is almost certainly not the only stressor affecting freshwater mussels.
      Metals, such as copper (Cu), are a common source of toxicant exposure in aquatic
      environments. The toxic effects of Cu on the early life stages of freshwater
      mussels have been well studied, and freshwater mussels are more sensitive to Cu
      than most aquatic organisms. The purpose of the present study was to determine
      the effect of a sublethal copper concentration on the upper thermal tolerance of
      three species, Lampsilis siliquoidea, Potamilus alatus, and Ligumia recta, of
      juvenile freshwater mussels in 48- and 96-h tests. Thermal tolerance was
      determined over a range of experimental temperatures (20-42 degrees C) at three
      acclimation temperatures (17, 22, and 27 degrees C). Median lethal temperatures
      (LT50s) were calculated in the absence and presence of Cu, and at 48 h ranged
      from 34.6 to 44.4 degrees C (mean 37.7 degrees C) without Cu, and from 33.8 to
      38.9 degrees C (mean 35.8 degrees C) with Cu. The LT50s at 96 h ranged from 32.5
      to 35.6 degrees C (mean 34.5 degrees C) without Cu and from 33.0 to 35.4 degrees
      C (mean 34.2 degrees C) with Cu. Potamilus alatus had a significantly lower 48 h
      LT50 with Cu than without Cu at the 22 degrees C acclimation temperature; there
      were no other significant differences in LT50s attributed to Cu. Survival trends
      showed limited evidence of interactive effects between copper and temperature for
      all three species, suggesting the combined stress of elevated temperatures and
      copper exposure to freshwater mussels should be further explored.

PMID- 20821497
TI  - Polychlorinated biphenyl elimination rates and changes in chemical activity in
      hibernating amphibians.
AB  - The present study examined polychlorinated biphenyl (PCB) elimination rates in
      overwintering green frogs (Rana clamitans) to determine if changes in chemical
      activity occurred during hibernation. Adult green frogs were dosed with a 1:1:1
      ratio of Aroclors 1248:1254:1260 in sunflower oil and allowed to enter into
      hibernation. Frogs were collected at four time points over the course of 85 days.
      Significant PCB elimination rates ranged from 0.0027 to 0.0376 d(-1). A negative
      correlation was found between K(OW) and elimination rate. Over the course of the
      present study, a decrease in total body percent lipid was measured. There was an
      overall increase in fugacity of higher K(OW) compounds corresponding to the
      relatively rapid decrease in lipid content. Congeners in metabolic group 2 (meta
      para vicinal hydrogen atoms) were preferentially eliminated over those in
      metabolic group 3 (ortho-meta vicinal hydrogen atoms), suggesting that
      biotransformation was occurring during hibernation. It was concluded that
      metabolic activity during hibernation, associated with water temperature, was
      sufficiently high to reduce lipid concentrations and increase chemical activity
      in emerging adults.

PMID- 20821498
TI  - Bioavailability of a natural lead-contaminated invertebrate diet to zebrafish.
AB  - Dietary metals are increasingly recognized as key determinants of total metal
      burdens in fish, yet their ecotoxicological significance remains unclear. In this
      study, a pairwise experimental design was used to assess reproductive performance
      of zebrafish (Danio rerio) fed diets supplemented with a natural Pb-enriched
      polychaete, Nereis diversicolor. Zebrafish were fed 1% flake food (dry wt
      diet/wet wt fish/d), 1% brine shrimp, and 1% N. diversicolor collected from
      either Gannel estuary, Cornwall, United Kingdom (UK), an estuary with legacy Pb
      contamination, or Blackwater estuary, Essex, UK, a reference site with low
      background metal concentrations, for 63 d. Mean daily dietary doses of Pb were
      0.417 and 0.1 mg/kg/d (dry wt feed:wet wt fish) for fish fed N. diversicolor from
      Gannel and Blackwater estuaries, respectively. With the exception of Ag, which
      was higher for fish fed N. diversicolor from Gannel estuary, there were no
      differences in daily dietary exposures to other metals (As, Cd, Cu, Fe, and Zn)
      between treatment groups. Fish fed Pb-enriched Gannel N. diversicolor exhibited
      no significant impairment to incidence of spawning, numbers of eggs per breeding
      pair or hatch rate of embryos compared with pre-exposure levels, when N.
      diversicolor was omitted from the dietary regimen. Nevertheless, metal analysis
      revealed significant increases in whole-body Pb burdens of male fish fed
      polychaetes from Gannel estuary, Ag in female fish fed Gannel worms, and Ag and
      Cd in male fish fed the Blackwater worms. These data demonstrate that Pb
      naturally incorporated in N. diversicolor is bioavailable to fish, and fish
      exhibit sex-dependent dietary metal accumulation patterns, but after 63 d of the
      experimental feeding regimen, reproductive performance was unaffected.

PMID- 20821499
TI  - Commercially manufactured engineered nanomaterials for environmental and health
      studies: important insights provided by independent characterization.
AB  - Environmental and health studies on nanomaterials are appearing in the literature
      at a rapid pace. These studies will address important issues related to the
      environmental health and safety (EHS) of nanomaterials. As noted in many recent
      workshop and agency reports, studies devoted toward the environmental fate and
      transport, nanomaterial-biological interactions, toxicity, and overall risk
      assessment of nanomaterials should have nanomaterial characterization as a
      central component of the study design. This aspect of the study design is
      necessary so that risks associated with nanomaterials can be fully understood and
      related to specific material properties. For studies that use commercially
      manufactured nanomaterials, the company often provides characterization data
      (e.g., chemical composition, phase, and size) of the purchased materials. One
      question is, how good are these data? Another is, what methods of analysis are
      used to characterize the properties of commercial nanomaterials? In the present
      study, some examples are presented that show marked differences between
      independent characterization of commercially manufactured nanomaterials and that
      provided by the company. Furthermore, information provided by the manufacturer
      may be incomplete and nonrepresentative of the entire sample and, in some cases,
      the information can, in fact, be wrong. Thus, the current study demonstrates an
      important need for independent characterization data in EHS studies of purchased
      materials.

PMID- 20821500
TI  - Accumulation and DNA damage in fathead minnows (Pimephales promelas) exposed to 2
      brominated flame-retardant mixtures, Firemaster 550 and Firemaster BZ-54.
AB  - Firemaster 550 and Firemaster BZ-54 are two brominated formulations that are in
      use as replacements for polybrominated diphenyl ether (PBDE) flame retardants.
      Two major components of these mixtures are 2,3,4,5-tetrabromo-ethylhexylbenzoate
      (TBB) and 2,3,4,5-tetrabromo-bis(2-ethylhexyl) phthalate (TBPH). Both have been
      measured in environmental matrices; however, scant toxicological information
      exists. The present study aimed to determine if these brominated flame-retardant
      formulations are bioavailable and adversely affect DNA integrity in fish. Fathead
      minnows (Pimephales promelas) were orally exposed to either FM 550, FM BZ54, or
      the nonbrominated form of TBPH, di-(2-ethylhexyl) phthalate (DEHP) for 56 d and
      depurated (e.g., fed clean food) for 22 d. At several time points, liver and
      blood cells were collected and assessed for DNA damage. Homogenized fish tissues
      were extracted and analyzed on day 0 and day 56 to determine the residue of TBB
      and TBPH and the appearance of any metabolites using gas chromatography-electron
      capture negative ion mass spectrometry (GC/ECNI-MS). Significant increases (p <
      0.05) in DNA strand breaks from liver cells (but not blood cells) were observed
      during the exposure period compared with controls, although during depuration
      these levels returned to control. Both parent compounds, TBB and TBPH, were
      detected in tissues at approximately 1% of daily dosage along with brominated
      metabolites. The present study provides evidence for accumulation, metabolism,
      and genotoxicity of these new formulation flame retardants in fish and highlights
      the potential adverse effects of TBB- and TBPH-formulated fire retardants to
      aquatic species.

PMID- 20821501
TI  - Adverse outcome pathways: a conceptual framework to support ecotoxicology
      research and risk assessment.
AB  - Ecological risk assessors face increasing demands to assess more chemicals, with
      greater speed and accuracy, and to do so using fewer resources and experimental
      animals. New approaches in biological and computational sciences may be able to
      generate mechanistic information that could help in meeting these challenges.
      However, to use mechanistic data to support chemical assessments, there is a need
      for effective translation of this information into endpoints meaningful to
      ecological risk-effects on survival, development, and reproduction in individual
      organisms and, by extension, impacts on populations. Here we discuss a framework
      designed for this purpose, the adverse outcome pathway (AOP). An AOP is a
      conceptual construct that portrays existing knowledge concerning the linkage
      between a direct molecular initiating event and an adverse outcome at a
      biological level of organization relevant to risk assessment. The practical
      utility of AOPs for ecological risk assessment of chemicals is illustrated using
      five case examples. The examples demonstrate how the AOP concept can focus
      toxicity testing in terms of species and endpoint selection, enhance across
      chemical extrapolation, and support prediction of mixture effects. The examples
      also show how AOPs facilitate use of molecular or biochemical endpoints
      (sometimes referred to as biomarkers) for forecasting chemical impacts on
      individuals and populations. In the concluding sections of the paper, we discuss
      how AOPs can help to guide research that supports chemical risk assessments and
      advocate for the incorporation of this approach into a broader systems biology
      framework.

PMID- 20821502
TI  - Bioavailability assessment of a contaminated field sediment from Patrick Bayou,
      Texas, USA: toxicity identification evaluation and equilibrium partitioning.
AB  - Contaminated sediments are commonly found in urbanized harbors. At sufficiently
      high contaminant levels, sediments can cause toxicity to aquatic organisms and
      impair benthic communities. As a result, remediation is necessary and diagnosing
      the cause of sediment toxicity becomes imperative. In the present study, six
      sediments from a highly industrialized area in Patrick Bayou (TX, USA) were
      subjected to initial toxicity testing with the mysid, Americamysis bahia, and the
      amphipod, Ampelisca abdita. All sediments were toxic to the amphipods, while
      sites PB4A, PB6A, and PB9 were the only sites toxic to mysids. Due to its
      toxicity to both test organisms, site PB6A was chosen for a marine whole sediment
      phase I toxicity identification evaluation (TIE). Results of the TIE found
      toxicity to amphipods was primarily due to nonionic organic contaminants (NOCs),
      rather than cationic metals or ammonia. Causes of mysid toxicity in the TIE were
      less clear. An assessment of metal bioavailability using equilibrium partitioning
      (EqP) approaches supported the results of the TIE that cationic metals were not
      responsible for observed toxicity in PB6A for either organism. Toxic units (TU)
      calculated on measured concentrations of NOCs in the sediment yielded a total TU
      of 1.25, indicating these contaminants are contributing to the observed sediment
      toxicity. Using a combination of these TIE and EqP assessment tools, this
      investigation was capable of identifying NOCs as the likely class of contaminants
      causing acute toxicity to amphipods exposed to Patrick Bayou sediment. The cause
      of mysid toxicity was not definitively determined, but unmeasured NOCs are
      suspected.

PMID- 20821503
TI  - Sampling in the Great Lakes for pharmaceuticals, personal care products, and
      endocrine-disrupting substances using the passive polar organic chemical
      integrative sampler.
AB  - The passive polar organic chemical integrative sampler in the pharmaceutical
      configuration (i.e., pharmaceutical-POCIS) was calibrated for sampling at water
      temperatures of 5, 15 and 25 degrees C to determine the influence of temperature
      on chemical-specific sampling rates (R(S)), thus providing more robust estimates
      of the time-weighted average concentrations of pharmaceuticals and personal care
      products (PPCPs) and endocrine-disrupting substances (EDS) in surface water. The
      effect of water temperature and flow on the R(S) of these analytes was evaluated
      in the laboratory with a static system. The loss of the test compounds from water
      by uptake into POCIS was linear over an 8-d period, and these experimental data
      yielded R(S) values in the range of 0.07 to 2.46 L/d across the temperature range
      for the 30 compounds tested. Water temperature and flow influenced POCIS uptake
      rates, but these effects were relatively small, which is consistent with the
      theory for uptake into POCIS samplers. Therefore, under a narrow range of water
      temperatures and flows, it may not be necessary to adjust the R(S) for POCIS.
      Except for acidic drugs and sulfonamide antibiotics, R(S) values were positively
      correlated with octanol-water partition coefficients (log K(OW)) of the test
      compounds. A linear relationship was also observed between R(S) and
      chromatographic retention times on a C18 reversed-phase column. These
      observations may provide a rapid method for estimating the R(S) of additional
      chemicals in the POCIS. The application of the R(S) to POCIS deployed for one
      month in Lake Ontario, Canada, during the summers of 2006 and 2008 yielded
      estimates of PPCP and EDS concentrations that are consistent with conventional
      concentration measurements of these compounds in Lake Ontario surface water.

PMID- 20821504
TI  - UO(2) 2+ speciation determines uranium toxicity and bioaccumulation in an
      environmental Pseudomonas sp. isolate.
AB  - In the present study, experiments were performed to investigate how
      representative cellulosic breakdown products, when serving as growth substrates
      under aerobic conditions, affect hexavalent uranyl cation (UO(2) (2+)) toxicity
      and bioaccumulation within a Pseudomonas sp. isolate (designated isolate A).
      Isolate A taken from the Cold Test Pit South (CTPS) region of the Idaho National
      Laboratory (INL), Idaho Falls, ID, USA. The INL houses low-level uranium
      contaminated cellulosic material and understanding how this material, and
      specifically its breakdown products, affect U-bacterial interactions is important
      for understanding UO(2) (2+) fate and mobility. Toxicity was modeled using a
      generalized Monod expression. Butyrate, dextrose, ethanol, and lactate served as
      growth substrates. The potential contribution of bicarbonate species present in
      high concentrations was also investigated and compared with toxicity and
      bioaccumulation patterns seen in low-bicarbonate conditions. Isolate A was
      significantly more sensitive to UO(2) (2+) and accumulated significantly more
      UO(2) (2+) in low-bicarbonate concentrations. In addition, UO(2) (2+) growth
      inhibition and bioaccumulation varied depending on the growth substrate. In the
      presence of high bicarbonate concentrations, sensitivity to UO(2) (2+) inhibition
      was greatly mitigated, and did not vary between the four substrates tested. The
      extent of UO(2) (2+) accumulation was also diminished. The observed patterns were
      related to UO(2) (2+) aqueous complexation, as predicted by MINTEQ (ver. 2.52)
      (Easton, PA, USA). In the low- bicarbonate medium, the presence of positively
      charged and unstable UO(2) (2+)-hydroxide complexes explained both the greater
      sensitivity of isolate A to UO(2) (2+), and the ability of isolate A to
      accumulate significant amounts of UO(2) (2+). The exclusive presence of
      negatively charged and stable UO(2) (2+)-carbonate complexes in the high bi
      carbonate medium explained the diminished sensitivity of isolate A to UO(2) (2+)
      toxicity, and limited ability of isolate A to accumulate UO(2) (2+).

PMID- 20821505
TI  - Application of a congener-specific debromination model to study
      photodebromination, anaerobic microbial debromination, and FE0 reduction of
      polybrominated diphenyl ethers.
AB  - A model was used to predict the photodebromination of the BDE-203, 197, 196, and
      153, the major components of the octa-polybrominated diphenyl ether (PBDE)
      technical mixture, as well as BDE-47, and the predicted results were compared to
      the experimental results. The predicted reaction time profiles of the
      photodebromination products correlate well with the experimental results. In
      addition, the slope of the linear regression between the measured product
      concentrations of the first step of the photodebromination products and their
      enthalpies of formation was found to be close to their theoretical value. The
      photodebromination results of the octa-BDE technical mixture were compared with
      anaerobic microbial debromination results and were found to be the same in both
      experiments. The debromination pathways of technical octa-BDE mixture were
      identified and BDE-154, 99, 47, and 31 were found to be the most abundant hexa-,
      penta-, tetra-, and tri-BDE debromination products, respectively. In addition to
      photodebromination and anaerobic biodebromination, the model prediction was also
      compared to the zero-valent iron reduction of BDE-209, 100, and 47 and the same
      debromination products were observed. Good correlation was observed between the
      photodebromination rate constants of fifteen PBDE congeners and their calculated
      lowest unoccupied molecular orbital (LUMO) energies, indicating that PBDE
      photodebromination is caused by electron transfer. Furthermore, the rate
      constants for the three different PBDE debromination processes are controlled by
      C-Br bond dissociation energy. With the model from the present study, the major
      debromination products for any PBDE congener released into the environment can be
      predicted.

PMID- 20821506
TI  - Bioaccumulation and biotransformation of pyrene and 1-hydroxypyrene by the marine
      whelk Buccinum undatum.
AB  - The fates of a phenolic contaminant and its hydrocarbon precursor have rarely
      been compared, especially in an invertebrate species. Two groups of Buccinum
      undatum were exposed to equimolar amounts of pyrene and 1-hydroxypyrene over 15 d
      through their diets. Tissue extracts from the muscle and visceral mass were
      analyzed by liquid chromatography with fluorescence and mass spectrometry
      detection. Nine biotransformation products were detected in animals from both
      exposures. These included 1-hydroxypyrene, pyrene-1-sulfate, pyrene-1
      glucuronide, pyrene glucose sulfate, two isomers each of pyrenediol sulfate and
      pyrenediol disulfate, and one isomer of pyrenediol glucuronide sulfate. These
      compounds represent a more complex metabolic pathway for pyrene than is typically
      reported. Diconjugated metabolites were as important in animals exposed to pyrene
      as in those exposed to 1-hydroxypyrene. Biotransformation products represented
      >90% of the material detected in the animals and highlight the importance of
      analyzing metabolites when assessing exposure. A mean of only 2 to 3% of the body
      burden was present in muscle compared with the visceral mass of both groups. The
      analytical methods were sufficiently sensitive to detect biotransformation
      products both in laboratory control whelks and in those sampled offshore. The
      tissue distribution of [(14)C]pyrene was also studied by autoradiography.
      Radioactivity was present primarily in the digestive and excretory system of the
      whelks and not in the gonads or muscle tissue.

PMID- 20821507
TI  - A multimedia activity model for ionizable compounds: validation study with 2,4
      dichlorophenoxyacetic acid, aniline, and trimethoprim.
AB  - Fugacity models are widely adopted for the environmental exposure assessment of
      organic chemicals but are inconvenient for nonvolatile substances, such as
      ionizable chemicals. The activity approach is a robust alternative to the
      fugacity concept and provides the thermodynamically exact equations to describe
      the behavior of neutral and ionizable molecules in nonideal systems. A multimedia
      activity model applicable to neutral and ionizable molecules (MAMI) was developed
      and tested for 2,4-dichlorophenoxyacetic acid and the bases aniline and
      trimethoprim. The model features pH and ionic strength dependence and species
      specific estimations of partition coefficients from physicochemical properties.
      Sorption estimates consider both lipophilic and electrical interactions. A
      realistic regional exposure scenario was simulated for the three test compounds,
      and model results were compared with results obtained with a conventional
      fugacity model and with monitoring data. The better performance of MAMI indicates
      that the activity approach can enlarge the applicability domain and improve model
      predictions of existing regional models. Model results, supported by experimental
      evidence, showed the importance of dissociation, electrical interactions in
      solids, humidity in air, and to a lesser extent salinity in seawater to describe
      the environmental fate of ionizable organic chemicals.

PMID- 20821508
TI  - Leaching potential of nonsteroidal anti-inflammatory drugs in soils.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) in soils resulting from application
      of municipal wastewater or biosolids may migrate through soils intact or be
      transformed and reach groundwater. In the present study, the leaching potential
      of four NSAIDs (ibuprofen, naproxen, ketoprofen, and diclofenac sodium) in three
      U.S. cropland soils was evaluated, and the effect of CaCl(2) solution (as an
      index of salinity), dissolved organic matter (DOM), and polyacrylamide (PAM)
      amendment was investigated. The soils were spiked with selected NSAIDs, incubated
      for 24 h followed by 7-d storage in glass flasks, and then packed into stainless
      steel columns and leached with deionized water (DIW), 10 mM CaCl(2), DOM (DOC 34
      mg/L), and PAM solution (1.0 mg/L) by gravity. Initial concentrations of
      ibuprofen, naproxen, ketoprofen, and diclofenac sodium in the three packed soils
      were 1.93 to 2.07, 1.74 to 2.27, 1.79 to 2.16, and 1.99 to 2.13 mg/kg,
      respectively. Maximum concentrations of the above NSAIDs in column effluents were
      1.23, 0.92, 0.69, and 1.12 mg/L, respectively, when the soil was leached with 10
      pore volumes of water, which occupied 17.4, 11.1, 9.6, and 15.2% of the total
      chemicals in each soil column. Dissolved organic matter or PAM solution did not
      facilitate the NSAIDs release from soils. The CaCl(2) solution, however, reduced
      the amounts of NSAIDs leached from all three soils. Leaching of NSAIDs differed
      among the three tested soils. The results suggest that the leaching of NSAIDs
      through soil to water is significant, and the mobility of NSAIDs in soil is
      related to their chemicals' characteristics (such as pK(a) values) and soil
      properties (such as soil organic matter and clay content). Amending soil with DOM
      or PAM does not significantly affect the leaching behavior of NSAIDs in soil,
      whereas increasing the salinity of the irrigation water may decrease the extent
      of contamination of groundwater posed by NSAIDs.

PMID- 20821509
TI  - Volatilization of monoaromatic compounds (benzene, toluene, and xylenes; BTX)
      from gasoline: effect of the ethanol.
AB  - The main objective of present study was to assess the evaporation profile of
      monoaromatic compounds, namely, benzene, toluene, and xylenes (BTX) from gasoline
      ethanol-blend fuels. The vapors from two river sand columns contaminated with
      gasoline and gasoline-ethanol were monitored for 77 d. Standards mixtures (batch
      tests) of benzene, toluene, and xylenes with different ethanol contents were also
      analyzed for evaporation rates studies. The instrumental analysis was performed
      via gas chromatography. The concentration of benzene in the vapor phase of the
      gasoline-ethanol column was decreased by 89.09%, considering the entire
      experimental period, whereas the toluene and xylenes concentrations were
      increased by 239.34 and 251.78%, respectively. In the batch tests, the benzene
      concentration in the vapor phase varied from 0.4 to 0.9 mg/L for ethanol
      concentrations (v/v) of 5 and 10%, respectively. For ethanol concentrations
      higher than 10%, no important changes in the benzene concentration were observed.
      The toluene exponentially increases between 20 and 30% ethanol concentration. and
      the maximum concentration of xylenes was observed when the ethanol concentration
      was 20% (v/v). These results suggest that the benzene evaporation behavior is
      preferentially affected by the interactions among ethanol and other aromatic
      compounds rather than the ethanol concentration itself. The evaporation behaviors
      of toluene and xylenes are directly dependent on the ethanol content.

PMID- 20821510
TI  - Pyrethroid insecticide concentrations and toxicity in streambed sediments and
      loads in surface waters of the San Joaquin Valley, California, USA.
AB  - Pyrethroid insecticide use in California, USA, is growing, and there is a need to
      understand the fate of these compounds in the environment. Concentrations and
      toxicity were assessed in streambed sediment of the San Joaquin Valley of
      California, one of the most productive agricultural regions of the United States.
      Concentrations were also measured in the suspended sediment associated with
      irrigation or storm-water runoff, and mass loads during storms were calculated.
      Western valley streambed sediments were frequently toxic to the amphipod,
      Hyalella azteca, with most of the toxicity attributable to bifenthrin and
      cyhalothrin. Up to 100% mortality was observed in some locations with
      concentrations of some pyrethroids up to 20 ng/g. The western San Joaquin Valley
      streams are mostly small watersheds with clay soils, and sediment-laden
      irrigation runoff transports pyrethroid insecticides throughout the growing
      season. In contrast, eastern tributaries and the San Joaquin River had low bed
      sediment concentrations (<1 ng/g) and little or no toxicity because of the
      preponderance of sandy soils and sediments. Bifenthrin, cyhalothrin, and
      permethrin were the most frequently detected pyrethroids in irrigation and storm
      water runoff. Esfenvalerate, fenpropathrin, and resmethrin were also detected.
      All sampled streams contributed to the insecticide load of the San Joaquin River
      during storms, but some compounds detected in the smaller creeks were not
      detected in the San Joaquin River. The two smallest streams, Ingram and Hospital
      Creeks, which had high sediment toxicity during the irrigation season, accounted
      for less than 5% of the total discharge of the San Joaquin River during storm
      conditions, and as a result their contribution to the pyrethroid mass load of the
      larger river was minimal.

PMID- 20821511
TI  - Geographic variation of persistent organic pollutant levels in humpback whale
      (Megaptera novaeangliae) feeding areas of the North Pacific and North Atlantic.
AB  - Seasonal feeding behavior and high fidelity to feeding areas allow humpback
      whales (Megaptera novaeangliae) to be used as biological indicators of regional
      contamination. Biopsy blubber samples from male individuals (n = 67) were
      collected through SPLASH, a multinational research project, in eight North
      Pacific feeding grounds. Additional male samples (n = 20) were collected from one
      North Atlantic feeding ground. Persistent organic pollutants were measured in the
      samples and used to assess contaminant distribution in the study areas. North
      Atlantic (Gulf of Maine) whales were more contaminated than North Pacific whales,
      showing the highest levels of polychlorinated biphenyls (PCBs), polybrominated
      diphenyl ethers (PBDEs), and chlordanes. The highest
      dichlorodiphenyltrichloroethane (DDT) levels were detected in whales feeding off
      southern California, USA. High-latitude regions were characterized by elevated
      levels of hexachlorocyclohexanes (HCHs) but generally nondetectable
      concentrations of PBDEs. Age was shown to have a positive relationship with
      SigmaPCBs, SigmaDDTs, Sigmachlordanes, and total percent lipid. Contaminant
      levels in humpback whales were comparable to other mysticetes and lower than
      those found in odontocete cetaceans and pinnipeds. Although these concentrations
      likely do not represent a significant conservation threat, levels in the Gulf of
      Maine and southern California may warrant further study.

PMID- 20821512
TI  - Influences of soil properties and leaching on copper toxicity to barley root
      elongation.
AB  - The relationships developed between soil properties and phytotoxicity threshold
      values for copper require validation in a wide range of soils with different
      properties and climate characteristics before they can be applied for regulatory
      purposes in countries throughout the world. Seventeen soils, which are
      representative of the major soil types and properties in China, were spiked with
      Cu chloride. A subset of the Cu-spiked soils was leached with artificial rain
      water to compare toxicity with that in unleached soils. Barley root elongation
      tests were performed under controlled environmental conditions. The
      concentrations of added Cu causing a 50% inhibitory effect (EC50) ranged from 67
      to 1,129 mg/kg in unleached soils and from 88 to 1,255 mg/kg in leached soil.
      Compared with the unleached toxicity thresholds, the leached EC10 (10%
      inhibition) and EC50 were higher by an average of 1.43- and 1.15-fold,
      respectively. Soil leaching significantly (p <or= 0.05) decreased the toxicity of
      Cu in approximately 35% of the soils. In this study, no single soil property was
      found to explain over 35% of the variance in (log transformed) EC50. However,
      stepwise multiple regressions using soil pH, organic carbon (OC) content, and
      effective cation exchange capacity (eCEC) were found to explain over 80% of the
      variance in Cu toxicity across soils. The model developed for Chinese soils based
      on these factors was found to predict significantly (r(2), 0.90) the
      phytotoxicity of Cu in European soils. These quantitative relationships between
      Cu toxicity and soil properties are helpful for developing soil-specific guidance
      on Cu toxicity thresholds.

PMID- 20821513
TI  - Analysis, occurrence, and toxic potential of pyrethroids, and fipronil in
      sediments from an urban estuary.
AB  - Eight pyrethroids and fipronil and its three major degradates were analyzed in
      urban estuarine sediments that exhibited a range of toxic effects to an amphipod
      test species. Sediments from Ballona Creek, an urban estuary in Southern
      California (USA), collected during three dry season events were analyzed by gas
      chromatography with electron capture and negative chemical ionization mass
      spectrometric detection (GC-ECD and GC-NCI-MS). The two detection methods were in
      agreement for intermediate levels of pyrethroid contamination (10-50 ng/g dry wt)
      but deviated for both low and high concentrations (< 5 and > 50 ng/g). Sediments
      contained total pyrethroids as high as 473 ng/g with permethrin, bifenthrin, and
      cypermethrin as the most abundant compounds. In contrast, fipronil and its
      desulfinyl, sulfide, and sulfone degradates were detected at much lower levels
      (<or= 0.18-16 ng/g). Toxic units estimated for these compounds revealed that
      bifenthrin and cypermethrin were likely contributors to the mortality observed in
      tests with the estuarine amphipod Eohaustorius estuarius. Although fipronil was
      not a likely contributor to the observed mortality, the concentrations detected
      may be of concern for more sensitive crustacean species. Furthermore, the spatial
      pattern of pyrethroid contamination and potential toxicity was highly correlated
      with fine-grained substrate, which shifted to downstream stations within a three
      month period during the dry season.

PMID- 20821514
TI  - Contaminant pattern and bioaccumulation of legacy and emerging organhalogen
      pollutants in the aquatic biota from an e-waste recycling region in South China.
AB  - Legacy pollutants, polychlorinated biphenyls (PCBs), dichlorodiphenyl
      trichloroethane and its metabolites (DDTs), and some emerging organhalogen
      pollutants, such as polybrominated diphenyl ethers (PBDEs), hexabromobenzene
      (HBB), pentabromotoluene (PBT), 2,3,4,5,6-pentabromoethyl benzene (PBEB), 1,2-bis
      (2,4,6-tribromophenoxy) ethane (BTBPE), and dechlorane plus (DP), were detected
      in an aquatic food chain (invertebrates and fish) from an e-waste recycling
      region in South China. Polychlorinated biphenyls, DDTs, PBDEs, and HBB were
      detected in more than 90% of the samples, with respective concentrations ranging
      from not detected (ND)-32,000 ng/g lipid weight, ND-850 ng/g lipid weight, 8 to
      1,300 ng/g lipid weight, and 0.28 to 240 ng/g lipid weight. Pentabromotoluene,
      PBEB, BTBPE, and DP were also quantifiable in collected samples with a
      concentration range of ND-40 ng/g lipid weight. The elevated levels of PCBs and
      PBDEs in the organisms, compared with those in non-e-waste regions in South
      China, suggest that these two kinds of pollutants derived mainly from e-waste
      recycling practices. Hexabromobenzene was significantly correlated with PBDEs,
      implying that HBB come from the release of e-waste along with PBDEs and/or the
      pyrolysis of BDE209. Most of the compounds whose trophic magnification factor
      (TMF) could be calculated were found to biomagnify (TMF > 1). Hexabromobenzene
      was also found, for the first time, to biomagnify in the present food web, with a
      TMF of 2.1.

PMID- 20821515
TI  - Bioavailability of decabromodiphenyl ether to the marine polychaete Nereis
      virens.
AB  - The flame retardant decabromodiphenyl ether (BDE 209) accumulates in humans and
      terrestrial food webs, but few studies have reported the accumulation of BDE 209
      in aquatic biota. To investigate the mechanisms controlling the bioavailability
      of BDE 209, a 28-d bioaccumulation experiment was conducted in which the marine
      polychaete worm Nereis virens was exposed to a decabromodiphenyl ether (deca-BDE)
      commercial mixture (>85% BDE 209) in spiked sediments, in spiked food, or in
      field sediments. Bioaccumulation from spiked substrate with maximum
      bioavailability demonstrated that BDE 209 accumulates in this species.
      Bioavailability depends on the exposure conditions, however, because BDE 209 in
      field sediments did not accumulate (<0.3 ng/g wet weight; 28-d biota-sediment
      accumulation factors [BSAFs] <0.001). When exposed to deca-BDE in spiked
      sediments also containing lower brominated congeners (a penta-BDE mixture),
      bioaccumulation of BDE 209 was 30 times lower than when exposed to deca-BDE
      alone. Selective accumulation of the lower brominated congeners supports their
      prevalence in higher trophic level species. The mechanisms responsible for
      limited accumulation of BDE 209 may involve characteristics of the sediment
      matrix and low transfer efficiency in the digestive fluid.

PMID- 20821516
TI  - Evaluation of the amphibian metamorphosis assay: exposure to the goitrogen
      methimazole and the endogenous thyroid hormone L-thyroxine.
AB  - The U.S. Environmental Protection Agency (U.S. EPA) has included an amphibian
      metamorphosis assay (AMA) to detect thyroid active chemicals in Tier 1 testing of
      their endocrine screening program. To understand the variability, specificity,
      and reliability of the key endpoints of this assay, two exposure studies with
      Xenopus laevis tadpoles were conducted with two known thyroid-active compounds,
      namely, methimazole or L-thyroxine, for a total of 21 d. In addition, various
      increased-flow-rate treatments were included in the exposures to evaluate the
      effects of physical stress on metamorphic development. The endpoints examined in
      the exposures were wet weight, snout-vent length, hind-limb length, developmental
      stage, and thyroid and gonadal histopathology. As expected, the results indicated
      that both methimazole and L-thyroxine were thyroid active in the AMA, hind-limb
      length and thyroid histopathology being the most sensitive endpoints of thyroid
      activity. Tadpoles that were exposed to the various physical stressors in these
      experiments showed no signs of altered metamorphic development, and exposure to
      the thyroid-active compounds had no effect on the developing gonad of X. laevis.
      Taken together, these results support the use of the AMA as a Tier 1 endocrine
      screen for detection of potential thyroid pathway activity; however, the lack of
      a true negative response (no-effect) during the validation process prevents a
      full evaluation of this assay's specificity at this time.

PMID- 20821517
TI  - 17alpha-ethinylestradiol induces an imbalance between apoptosis and cell
      proliferation to sex steroid disruption in a testis culture of gudgeon, Gobio
      gobio.
AB  - The aim of this study was to investigate the effect of the most potent
      xenoestrogen currently found in the environment, ethinylestradiol (EE2), on some
      physiological events occurring during early spermatogenesis of gudgeon (Gobio
      gobio), a common European fish species. Physiological pathways studies were
      apoptosis, cell proliferation, and steroidogenesis on sex steroids (testosterone
      [T], 11-ketotestosterone [11-KT], and 17beta-estradiol [E2]). Testis pieces were
      cultured in vitro during 21 d at 10(-4), 10(-3), 10(-2), 10(-1), 1 and 10
      microg/L of EE2 as well as in positive (10(-1) microg/L of E2) and ethanol
      control medium. Apoptosis and cell proliferation displayed opposite responses
      related to the EE2 concentration. When apoptosis inhibition was observed, cell
      proliferation was induced at 10(-2) and 10(-1) microg/L of EE2 as well as in the
      positive control. In contrast, a massive cell death was detected for high EE2
      concentrations (1 and 10 microg/L). Steroidogenesis was also disrupted in a dose
      related manner. 11-Ketotestosterone was depressed at 10(-2) and 10(-1) microg/L
      of EE2 whereas E2 was detectable in the medium only at 10(-3), 10(-2), and 10(-1)
      microg/L of EE2. High concentrations of T were detected in the medium at 10(-3),
      10(-2), and 10(-1) microg/L of EE2 but depressed at 1 and 10 microg/L of EE2. In
      conclusion, intermediate EE2 concentrations (10(-2) and 10(-1) microg/L) used in
      this experimental design have obviously disrupted early spermatogenesis, leading
      to an imbalance between cell death and cell proliferation in a sex steroid
      environment toward E2. The results of the present study could be the basis
      conditions for oocyte development within the testis of a common teleost fish
      under xenoestrogen exposure.

PMID- 20821518
TI  - Effect of aluminum on cellular division and photosynthetic electron transport in
      Euglena gracilis and Chlamydomonas acidophila.
AB  - The present study investigated aluminum's effect on cellular division and the
      photosynthetic processes in Euglena gracilis and Chlamydomonas acidophila at pH
      3.0, at which Al is present mostly as Al(3+), AlSO(4) (+), and Al(SO(4))(2) (-).
      These algal species were exposed to 100, 188, and 740 microM Al, and after 24 h
      cell-bound Al was significantly different from control only for the highest
      concentration tested. However, very different effects of Al on algal cellular
      division, biomass per cell, and photosynthetic activity were found. Aluminum
      stimulated cell division but decreased at some level biomass per cell in C.
      acidophila. Primary photochemistry of photosynthesis, as Photosystem II quantum
      yield, and energy dissipation via nonphotochemical activity were slightly
      affected. However, for E. gracilis, under the same conditions, Al did not show a
      stimulating effect on cellular division or photosynthetic activity. Primary
      photochemical activity was diminished, and energy dissipation via
      nonphotochemical pathways was strongly increased. Therefore, when Al is highly
      available in aquatic ecosystems, these effects may indicate very different
      response mechanisms that are dependent on algal species.

PMID- 20821519
TI  - Effect assessment of the herbicide paraquat on a green alga using differential
      gene expression and biochemical biomarkers.
AB  - Effects of the herbicide paraquat were assessed on the green freshwater alga
      Chlamydomonas reinhardtii using different endpoints of toxicity. Cell
      concentration and growth rate were monitored, whereas flow cytometry was applied
      to determine changes in chlorophyll content, viability and presence of reactive
      oxygen species. Furthermore, a transcriptomics approach using microarray
      hybridizations was applied to elucidate the mechanisms of toxicity. The results
      reveal that paraquat concentrations above 0.25 microM induce toxic effects in C.
      reinhardtii, reflected in a significantly reduced growth rate and cell
      concentration with a corresponding median effective concentration (EC50) value of
      0.26 microM. With increasing paraquat concentrations, an increase in cell volume
      was registered with a particle counter as well as in the forward scattering
      signal of flow cytometric measurements, which is a measure of cell size. Flow
      cytometry, moreover, showed an increase in reactive oxygen species with
      increasing exposure concentration, corroborating the general knowledge that this
      herbicide exerts its toxicity through the generation of oxidative stress. At the
      same time, several genes involved in oxidative stress defense mechanisms, such as
      L-ascorbate peroxidase, glutaredoxin, and a possible glutathione-S-transferase
      were differentially expressed, demonstrating the value of microarrays for
      elucidating possible mechanisms of toxicity. The fact that several genes were
      differentially expressed at paraquat concentrations that caused no adverse
      effects on higher levels of biological organization indicates that a
      transcriptomics approach allows for the detection of early effects, even before
      they become manifest at higher levels.

PMID- 20821520
TI  - Insights into the development of fungal biomarkers for metal ecotoxicity
      assessment: case of Trametes versicolor exposed to copper.
AB  - The relationship between the physiological state of fungi and the response of
      their functional system to metals is not known, limiting the use of fungal
      enzymes as tools for assessing metal ecotoxicity in terrestrial ecosystems. The
      present study attempts to establish how the development phases modulate the
      secretion of enzymes in the filamentous fungus Trametes versicolor after exposure
      to Cu. For that purpose, extracellular hydrolases (acid and alkaline
      phosphatases, aryl-sulfatase, beta-glucosidase, beta-galactosidase, and N-acetyl
      beta-glucosaminidase) and oxidoreductases (laccase, manganese and lignin
      peroxidases) were monitored in liquid cultures for 2 weeks. Copper was added
      during either the growth or the stationary phases at 20 or 200 ppm. Results of
      the present study showed that Cu at the highest concentration modifies the
      secretion of enzymes, regardless of the development phase to which the fungus was
      exposed. However, the sensitivity of enzyme responses to Cu depended on the phase
      development and the type of secreted enzyme. In a general way, the production of
      hydrolases was decreased by Cu, whereas that of oxidoreductases was highly
      increased. Furthermore, lignin peroxidase was not detected in control cultures
      and was specifically produced in the presence of Cu. In conclusion, fungal
      oxidoreductases may be enzymatic biomarkers of copper exposure for ecotoxicity
      assessment.

PMID- 20821521
TI  - Effects of egg order on organic and inorganic element concentrations and egg
      characteristics in tree swallows, Tachycineta bicolor.
AB  - The laying order of tree swallow eggs was identified from the Housatonic River,
      Berkshire County, Massachusetts, USA, and eggs were chemically analyzed
      individually to document possible effects of laying order on organic contaminant
      and inorganic element concentrations. Effects of laying order on other parameters
      such as egg weight, size, and lipid and moisture content also were assessed. Some
      effects of egg order on total polychlorinated biphenyls (PCBs) were detected, but
      the effect was not uniform across individual females or between years. In 2004,
      clutches with higher total PCBs tended to have concentrations decline across egg
      order, whereas clutches with lower concentrations of PCBs tended to increase
      across egg order. In contrast, in 2005, there was a tendency for concentrations
      to increase across egg order. Polychlorinated biphenyl concentrations were highly
      variable within and among clutches in both years. The directionality of egg order
      associations (i.e., slopes) for trace elements was element dependent, was
      positive for Mn and Zn, was negative for B, and had no slope for Cr. Whole egg
      weight increased across egg order. Percentage lipid was variable within a clutch,
      with no pattern common across all females. Percentage lipid was also correlated
      with organic contaminant concentration. In highly contaminated environments,
      higher lipid content could have the unanticipated corollary of having higher
      concentrations of lipophilic contaminants such as PCBs. To reduce the effect of
      high variation within a clutch when assessing contamination exposure, it is
      recommended that two eggs per clutch be collected and pooled for chemical
      analysis. We further recommend that, as long as the two eggs are randomly
      collected, the additional effort needed to identify and collect specific eggs is
      not warranted.

PMID- 20821522
TI  - Physiological and potential genetic toxicity of chlortetracycline as an emerging
      pollutant in wheat (Triticum aestivum L.).
AB  - Increasing attention is now being paid to antibiotic contamination as a serious
      environmental issue. Chlortetracycline has been widely used for decades as a
      human and veterinary medicine, which has resulted in environmental residues and
      damage to living organisms. In the present study, the physiological and potential
      genetic toxicity of chlortetracycline was investigated using a wheat (Triticum
      aestivum L.) bioassay at a concentration range of 0.0625 to 300 mg/L and an
      exposure time of 24, 48, and 72 h. The results indicated that chlortetracycline
      at the lower concentrations stimulated germination and cell mitotic division and
      growth, whereas higher concentrations significantly inhibited processes such as
      bud length (50-300 mg/L), percentage germination (25-300 mg/L), root length (25
      300 mg/L), and mitotic index (MI) (25-300 mg/L). The lowest concentration of
      chlortetracycline slightly augmented the frequency of micronucleus (MN),
      chomosomal aberration (CA), and sister chomatid exchange (SCE) in the root tips;
      however, significant (p < 0.05 and 0.01) levels of augmentation were observed at
      higher concentrations in a concentration-dependent manner, including the
      frequencies of MN (25-200 mg/L), CA (10-200 mg/L), and SCE (5-200 mg/L),
      respectively. The inducement of MN, CA, and SCE decreased at 250 and 300 mg/L as
      a result of acute cell toxicity. In addition, all endpoints showed a time
      dependent increase at 0.0625 to 200 mg/L. These results imply that
      chlortetracycline (>or=5 mg/L) may be genotoxic to plant cells, and exposure to
      chlortetracycline may pose a potential genotoxic risk to living organisms.
      Comparatively, SCE was the most sensitive, followed by CA, and MN was the least
      sensitive to chlortetracycline genotoxicity in wheat. The results also suggest
      that the wheat bioassay is efficient, simple, and reproducible for monitoring the
      genotoxicity of chlortetracycline in the environment.

PMID- 20821523
TI  - Effects of pesticides and antibiotics on penaeid shrimp with special emphases on
      behavioral and biomarker responses.
AB  - The purpose of the present study is to provide information on the current state
      of knowledge regarding the effects of pesticides and antibiotics used in
      aquaculture on penaeid shrimp, one of the most common aquatic products for human
      consumption, with a special emphasis on the use of behavioral, physiological, and
      biochemical response. These include behavior; feeding rate changes; respiration
      rate, oxygen consumption, and osmoregulation alterations; nucleic acids, protein,
      and glycogen synthesis; cholinesterase activity inhibition; ATPase activity; and
      oxidative stress responses. This paper also deals with residues of antibiotics
      and pesticides in penaeid shrimp. Antibiotics and pesticides used in aquaculture
      may have adverse effects on treated animals and human consumers health if they
      are not correctly used. As a complement to the measurement of antibiotic and
      pesticide residues in tissues, the use of behavioral and biomarker responses can
      provide more relevant biological information on the potential adverse effects of
      antibiotics and pesticides on penaeid shrimp health.

PMID- 20821524
TI  - Genetic costs of tolerance to metals in Daphnia longispina populations
      historically exposed to a copper mine drainage.
AB  - The present study was conducted to assess three microevolutionary aspects of
      adaptation to pollution in Daphnia longispina populations historically exposed to
      an acid mine drainage from an abandoned pyrite mine: pollution mediated effects
      in acute tolerance to copper (Cu) and zinc (Zn); pollution-mediated effects on
      genetic variability of tolerant and physiological traits related to fitness
      (feeding rates); and fitness costs of tolerance measured as genetic trade-offs
      between tolerance and feeding rates under none and low levels of contamination.
      These objectives were addressed by comparing broad sense heritabilities and
      genetic correlations using up to 20 distinct clonal lineages randomly obtained
      from two populations: one located in a water reservoir contaminated by the acid
      mine drainage, and the other located in a nearby clean water reservoir. Results
      showed that only sensitive and resistant lineages to Cu were present in the
      reference and contaminated site, respectively. For Zn, however, both populations
      had a similar distribution pattern of sensitivities. Heritability values for
      tolerant and feeding traits across metal exposure levels was similar in both
      populations being in most cases greater than 50%. Fitness costs of tolerance were
      illustrated by lower feeding rates of the tolerant population compared to the
      reference one and negative genetic correlations between mean clonal feeding rates
      and median clonal survival time in control conditions (no added Cu or Zn). The
      results obtained thus support the view that tolerance to pollution is
      ecologically costly.

PMID- 20821525
TI  - Uptake and transport of roxarsone and its metabolites in water spinach as
      affected by phosphate supply.
AB  - Roxarsone (ROX) is widely used as a feed additive in intensive animal production.
      While an animal is fed with ROX, the As compounds in the manure primarily occur
      as ROX and its metabolites, including arsenate (As[V]), arsenite (As[III]),
      monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA). Animal manure is
      commonly land applied with phosphorous fertilizers in China. A pot experiment was
      conducted to investigate the phytoavailability of ROX, As(V), As(III), MMA, and
      DMA in water spinach (Ipomoea aquatica), with the soil amended with 0, 0.25,
      0.50, 1.0, and 2.0 g PO(4)/kg, respectively, plus 2% (w/w manure/soil) chicken
      manure (CM) bearing ROX and its metabolites. The results indicate that this
      species of water spinach cannot accumulate ROX and MMA at detectable levels, but
      As(V), As(III), and DMA were present in all plant samples. Increased phosphorous
      decreased the shoot As(V) and As(III) in water spinach but did not affect the
      root As(V). The shoot DMA and root As(III) and DMA were decreased/increased and
      then increased/decreased by elevated phosphorous. The total phosphorous content
      (P) in plant tissue did not correlate with the total As or the three As species
      in tissues. Arsenate, As(III), and DMA were more easily accumulated in the roots,
      and phosphate considerably inhibited their upward transport. Dimethylarsinic acid
      had higher transport efficiency than As(V) and As(III), but As(III) was dominant
      in tissues. Conclusively, phosphate had multiple effects on the accumulation and
      transport of ROX metabolites, which depended on their levels. However, proper
      utilization of phosphate fertilizer can decrease the accumulation of ROX
      metabolites in water spinach when treated with CM containing ROX and its
      metabolites.

PMID- 20821526
TI  - Investigating the link between pulp mill effluent and endocrine disruption:
      attempts to explain the presence of intersex fish in the Wabigoon River, Ontario,
      Canada.
AB  - The ability of some pulp mill effluents (PME) to act as reproductive and
      endocrine disrupters in fish is well documented in the literature. However,
      changes are not always consistent with regard to species, gender, hormones, or
      reproductive effects. In the present study, the presence of the first intersexed
      fish that, to our knowledge, has been found in a Canadian river exposed to PME,
      is reported. A field survey of the Wabigoon River near Dryden, Ontario, in the
      fall of 2000 found intersexed walleye (Sander vitreus vitreus) with significantly
      altered hormone levels and reduced gonad size. The Wabigoon River receives
      discharge from a bleached kraft pulp and paper mill and a municipal wastewater
      (MWW) plant. It also has historical sediment contamination (wood fiber mats)
      contributing to extended periods of low dissolved oxygen under low flow, drought
      conditions. A mesocosm-based partial life cycle test exposing fathead minnows
      (Pimephales promelas) to reference water, 20% effluent volume to river volume
      (v/v), 40% (v/v), or 60% (v/v) PME as well as a field survey of the walleye in
      the Wabigoon River were conducted. The only change in our mesocosm exposure was a
      decrease in testosterone in males with increasing effluent concentration and
      vitellogenin induction in males exposed to 60% (v/v) effluent. These results did
      not reflect the magnitude of endocrine disruption seen in the wild fish survey.
      Several hypotheses that may explain these discrepancies are proposed.
      Specifically, evidence is offered from published studies indicating that either
      hypoxia or MWW, alone or in combination with PME, may explain the discrepancy
      between our field experiment and the wild fish survey. The present study
      illustrates the complexities of multistressor receiving environments and the need
      for the development of cumulative effects assessment approaches.

PMID- 20821527
TI  - The antimicrobial triclocarban stimulates embryo production in the freshwater
      mudsnail Potamopyrgus antipodarum.
AB  - Recent research has indicated that the antimicrobial chemical triclocarban (TCC)
      represents a new type of endocrine disruptor, amplifying the transcriptional
      activity of steroid hormones and their receptors while itself exhibiting little
      affinity for these receptors. The effects of TCC were studied in the freshwater
      mudsnail Potamopyrgus antipodarum. Specimens were exposed to concentrations
      ranging from 0.05 to 10.5 microg/L dissolved TCC and were removed and dissected,
      and embryos contained within the brood pouch were counted and classified as
      shelled or unshelled after two and four weeks of exposure. After four weeks,
      environmentally relevant TCC concentrations of 1.6 to 10.5 microg/L resulted in
      statistically significant increases in the number of unshelled embryos, whereas
      0.2, 1.6, and 10.5 microg/L exposures significantly increased numbers of shelled
      embryos. The lowest observed effect concentration (LOEC) was 0.2 microg/L, the no
      observed effect concentration (NOEC) was 0.05 microg/L; the 10% effective
      concentration (EC10) and the median effective concentration (EC50) for unshelled
      effects were 0.5 microg/L and 2.5 microg/L, respectively. Given the widespread
      occurrence of TCC in the environment and the effects shown at environmentally
      relevant concentrations, these results indicate that TCC may be causing
      reproductive effects in the environment. Furthermore, the present study indicates
      that environmental risk from a new class of endocrine-disrupting chemicals (EDCs)
      is both qualitatively and quantitatively similar to risk from existing classes of
      EDCs.

PMID- 20821528
TI  - Oribatid mites in soil toxicity testing-the use of Oppia nitens (C.L. Koch) as a
      new test species.
AB  - Few soil invertebrate species are available for the toxic assessment of soils
      from boreal or other northern ecozones, yet these soils cover the majority of
      Canada's landmass as well as significant portions of Eurasia. Oppia nitens (C.L.
      Koch) is an herbivorous and fungivorous oribatid mite found in soil throughout
      Holarctic regions, including Canada. Soil tests using O. nitens were performed
      using 15 different forest soil types and horizons to investigate test variability
      in adult survival and reproduction. Adult survival (86.1 +/- 1.1%) was consistent
      across soil types, with a coefficient of variation (CV) of 15%. However,
      reproduction varied significantly, ranging from 2.9 (+/-1.1) to 86.2 (+/-11.7)
      individuals, with a corresponding CV of 118 and 30%, respectively. Of the soil
      factors assessed (NH(3), NO(3), pH, phosphorus [P], organic matter content (OM),
      carbon:nitrogen (C:N), sand, silt, clay, and sodium adsorption ratio), soil
      organic matter (OM) explained 68% of the variation observed for reproduction.
      Increasing the OM using Sphagnum sp. peat moss resulted in optimal reproduction
      at 7% OM (8% peat content) with the lowest variability (CV of 20%). When
      assessing the toxicity of a reference chemical, boric acid, the effect of peat
      amendment reduced lethality to adults with no observable difference on
      reproduction. The use an age-synchronized culture reduced the test variability
      for reproduction relative to the use of unsynchronized cultures. Oppia nitens is
      a good candidate species for a standardized test design, with adult survival
      easily assessed in a relatively simple design. A long-term reproduction test with
      O. nitens will require the use of a synchronized population and, on occasion, OM
      amendment when testing soils with low organic matter content.

PMID- 20821529
TI  - Mercury accumulation along a contamination gradient and nondestructive indices of
      bioaccumulation in amphibians.
AB  - Mercury (Hg) is an important environmental contaminant due to its global
      distribution, tendency to bioaccumulate, and toxicity in wildlife. However, Hg
      has received little attention in amphibians compared to other vertebrates.
      Amphibians vary widely in life history strategies and feeding ecologies, which
      could influence Hg exposure and accumulation. To determine whether species and
      life stage affects Hg bioaccumulation, adults from three species (Plethodon
      cinereus, Eurycea bislineata, and Bufo americanus) and larvae from the latter two
      species were collected along a contamination gradient on the South River (VA,
      USA). Total Hg (THg) concentrations in the contaminated site were 3.5 to 22 times
      higher than in the reference site. Differences were found in THg concentrations
      in amphibians that were consistent with their habitat requirements and feeding
      preferences. In general, adults (3,453 +/- 196 ng/g, dry mass) and larvae (2,479
      +/- 171 ng/g) of the most river-associated species, E. bislineata, had the
      highest THg concentrations, followed by B. americanus tadpoles (2,132 +/- 602
      ng/g), whereas adults of the more terrestrial B. americanus (598 +/- 117 ng/g)
      and P. cinereus (583 +/- 178 ng/g) had the lowest concentrations. In addition,
      nondestructive sampling techniques were developed. For the salamander species,
      THg concentrations in tail tissue were strongly correlated (r >or= 0.97) with the
      remaining carcass. A strong positive correlation (r = 0.92) also existed between
      blood and whole-body THg concentrations in B. americanus. These results suggest
      that amphibians and their terrestrial predators may be at risk of Hg exposure in
      this system and that nondestructive methods may be a viable sampling alternative
      that reduces impacts to local populations.

PMID- 20821530
TI  - Bioaccumulation and maternal transfer of mercury and selenium in amphibians.
AB  - Amphibian population declines have been documented worldwide and environmental
      contaminants are believed to contribute to some declines. Maternal transfer of
      bioaccumulated contaminants to offspring may be an important and overlooked
      mechanism of impaired reproductive success that affects amphibian populations.
      Mercury (Hg) is of particular concern due to its ubiquity in the environment,
      known toxicity to other wildlife, and complex relationships with other elements,
      such as selenium (Se). The objectives of the present study were to describe the
      relationships between total Hg (THg), methlymercury (MMHg), and Se in three
      amphibian species (Plethodon cinereus, Eurycea bislineata cirrigera, and Bufo
      americanus) along a Hg-polluted river and floodplain, and to determine if B.
      americanus maternally transfers Hg and Se to its eggs in a tissue residue
      dependent manner. Total Hg and MMHg concentrations in all species spanned two
      orders of magnitude between the reference and contaminated areas, while Se
      concentrations were generally low in all species at both sites. Strong positive
      relationships between THg and MMHg in tissues of all species were observed
      throughout. Both Hg and Se were maternally transferred from females to eggs in B.
      americanus, but the percentage of the females' Hg body burden transferred to eggs
      was low compared with Se. In addition, Hg concentrations appeared to positively
      influence the amount of Se transferred from female to eggs. The present study is
      the first to confirm a correlation between Hg concentrations in female carcass
      and eggs in amphibians and among the first to describe co-transference of Se and
      Hg in an anamniotic vertebrate. The results suggest future work is needed to
      determine whether maternal transfer of Hg has transgenerational implications for
      amphibian progeny.

PMID- 20821531
TI  - Role of soil interstitial water in the accumulation of hexahydro-1,3,5-trinitro
      1,3,5-triazine in the earthworm Eisenia andrei.
AB  - The uptake of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) from soil by the
      earthworm Eisenia andrei was examined by using the equilibrium partitioning (EqP)
      theory and a three-compartment model including soil (S), interstitial water (IW),
      and earthworms (E). The RDX concentrations were measured using U.S. Environmental
      Protection Agency (U.S. EPA) Method 8330A and high-performance liquid
      chromatography (HPLC). The S-IW studies were conducted using four natural soils
      with contrasting physicochemical properties that were hypothesized to affect the
      bioavailability of RDX. Each soil was amended with nominal RDX concentrations
      ranging from 1 to 10,000 mg/kg. The HPLC analysis showed that the IW extracted
      from soil was saturated with RDX at 80 mg/kg or greater soil concentrations. The
      calculated S-IW coefficient (K(p)) values for RDX ranged from 0.4 to 1.8 ml/g
      soil, depending on the soil type, and were influenced by the organic matter
      content. In the IW-E studies, earthworms were exposed to nonlethal RDX
      concentrations in aqueous media. The uptake of RDX by the earthworms correlated
      well (r(2) = 0.99) with the dissolved RDX concentrations. For the E-S studies,
      earthworms were exposed to RDX-amended soils used in the S-IW studies. The
      bioconcentration factors (BCF; ratios of E-to-IW RDX concentrations) were
      relatively constant ( approximately 5) up to 80 mg/kg soil RDX concentrations,
      which encompass the RDX saturation limit in the interstitial water of the tested
      soils. At this concentration range, the RDX uptake from interstitial water was
      likely dominated by passive diffusion and could be used as an indicator of
      bioavailability. Other mechanisms may be involved at greater RDX soil
      concentrations.

PMID- 20821532
TI  - Ecological models and pesticide risk assessment: current modeling practice.
AB  - Ecological risk assessments of pesticides usually focus on risk at the level of
      individuals, and are carried out by comparing exposure and toxicological
      endpoints. However, in most cases the protection goal is populations rather than
      individuals. On the population level, effects of pesticides depend not only on
      exposure and toxicity, but also on factors such as life history characteristics,
      population structure, timing of application, presence of refuges in time and
      space, and landscape structure. Ecological models can integrate such factors and
      have the potential to become important tools for the prediction of population
      level effects of exposure to pesticides, thus allowing extrapolations, for
      example, from laboratory to field. Indeed, a broad range of ecological models
      have been applied to chemical risk assessment in the scientific literature, but
      so far such models have only rarely been used to support regulatory risk
      assessments of pesticides. To better understand the reasons for this situation,
      the current modeling practice in this field was assessed in the present study.
      The scientific literature was searched for relevant models and assessed according
      to nine characteristics: model type, model complexity, toxicity measure, exposure
      pattern, other factors, taxonomic group, risk assessment endpoint,
      parameterization, and model evaluation. The present study found that, although
      most models were of a high scientific standard, many of them would need
      modification before they are suitable for regulatory risk assessments. The main
      shortcomings of currently available models in the context of regulatory pesticide
      risk assessments were identified. When ecological models are applied to
      regulatory risk assessments, we recommend reviewing these models according to the
      nine characteristics evaluated here.

PMID- 20821533
TI  - Modeling mercury biomagnification (South River, Virginia, USA) to inform river
      management decision making.
AB  - Mercury trophic transfer in the South River (VA, USA) was modeled to guide river
      remediation decision making. Sixteen different biota types were collected at six
      sites within 23 river miles. Mercury biomagnification was modeled using a general
      biomagnification model based on delta(15)N and distance from the historic mercury
      release. Methylmercury trophic transfer was clearer than that for total Hg and,
      therefore, was used to build the predictive model (r(2) (prediction) = 0.76). The
      methylmercury biomagnification factors were similar among sites, but model
      intercept did increase with distance down river. Minimum Akaike's Information
      Criterion Estimation (MAICE) justified the incorporation of distance in the
      model. A model with a very similar biomagnification factor to the South River
      (95% confidence intervals [CI] = 0.38-0.52) was produced for a second
      contaminated Virginia river, the North Fork Holston River (95% CI = 0.41-0.55).
      Percent of total Hg that was methylmercury increased monotonically with trophic
      position. Trophic models based on delta(15)N were adequate for predicting changes
      in mercury concentrations in edible fish under different remediation scenarios.

PMID- 20821534
TI  - Comment on: "Sorption of nitroaromatics to soils: Comparison of the importance of
      soil organic matter versus clay".

PMID- 20821536
TI  - Radioactive uranium measurement in vivo using a handheld interfaced analyzer.
AB  - A trace uranium (U) detection method was developed with a handheld voltammetric
      analyzer that was the size of a mobile phone, with working sensors made of simple
      graphite pencil electrode (PE). The optimum stripping voltammetric conditions
      were sought, and the following results were obtained: 0.0 to 0.08 ng/L working
      ranges and a statistically relative standard deviation of 1.78% (RSD; n=15) at a
      10.0 microg/L U spike. The experiment accumulation time used was only 150 s.
      Under this condition, the diagnostic detection limit approached 0.007 ng/L. The
      method was applied to soil of a natural rock in a radioactive mineralogy site.
      Earthworms that resided at this site were assayed. The method was found to be
      applicable in biological diagnosis or in real-time in vivo survey.

PMID- 20821537
TI  - Human exposure to polybrominated diphenyl ethers at production area, China.
AB  - The concentrations of polybrominated diphenyl ethers (PBDEs) were detected in air
      and aquatic products in PBDEs production areas which are located at the south
      coast area of Laizhou Bay, Shandong province, China in this study. Concentrations
      of SigmaPBDEs in the air ranged from 0.47 ng/m3 to 161 ng/m3. In aquatic
      products, concentrations of SigmaPBDEs ranged from 2.7 ng/g wet weight to 42 ng/g
      wet weight. The mean dietary intake of SigmaPBDEs via aquatic products
      consumption in this study was 218 ng/day. Daily intake of SigmaPBDEs via
      inhalation in this study was 612 ng for men and 455 ng for women. With a
      contribution of 80%, BDE-209 was predominant in the total intake. Dietary intake
      and breathing inhalation contributed 29 and 71%, respectively, to the total PBDEs
      intake. The results indicate that breathing inhalation also plays a very
      significant pathway for the population of the PBDEs production area. Compared
      with similar studies in other countries, human exposure to PBDEs via diet and
      inhalation in this study was the highest in the world.

PMID- 20821538
TI  - Possibilities and limitations of modeling environmental exposure to engineered
      nanomaterials by probabilistic material flow analysis.
AB  - Information on environmental concentrations is needed to assess the risks that
      engineered nanomaterials (ENM) may pose to the environment. In this study,
      predicted environmental concentrations (PEC) were modeled for nano-TiO2, carbon
      nanotubes (CNT) and nano-Ag for Switzerland. Based on a life-cycle perspective,
      the model considered as input parameters the production volumes of the ENMs, the
      manufacturing and consumption quantities of products containing those materials,
      and the fate and pathways of ENMs in natural and technical environments. Faced
      with a distinct scarcity of data, we used a probabilistic material flow analysis
      model, treating all parameters as probability distributions. The modeling
      included Monte Carlo and Markov Chain Monte Carlo simulations as well as a
      sensitivity and uncertainty analysis. The PEC values of the ENMs in the different
      environmental compartments vary widely due to different ENM production volumes
      and different life cycles of the nanoproducts. The use of ENM in products with
      high water relevance leads to higher water and sediment concentrations for nano
      TiO2 and nano-Ag, compared to CNTs, where smaller amounts of ENM reach the
      aquatic compartments. This study also presents a sensitivity analysis and a
      comprehensive discussion of the uncertainties of the simulation results and the
      limitations of the used approach. To estimate potential risks, the PEC values
      were compared to the predicted-no-effect concentrations (PNEC) derived from
      published data. The risk quotients (PEC/PNEC) for nano-TiO2 and nano-Ag were
      larger than one for treated wastewater and much smaller for all other
      environmental compartments (e.g., water, sediments, soils). We conclude that
      probabilistic modeling is very useful for predicting environmental concentrations
      of ENMs given the current lack of substantiated data.

PMID- 20821539
TI  - Fraction of organic carbon predicts labile desorption rates of chlorinated
      organic pollutants in laboratory-spiked geosorbents.
AB  - The resuspension of large volumes of sediments that are contaminated with
      chlorinated pollutants continues to threaten environmental quality and human
      health. Whereas kinetic models are more accurate for estimating the environmental
      impact of these events, their widespread use is substantially hampered by the
      need for costly, time-consuming, site-specific kinetics experiments. The present
      study investigated the development of a predictive model for desorption rates
      from easily measurable sorbent and pollutant properties by examining the
      relationship between the fraction of organic carbon (fOC) and labile release
      rates. Duplicate desorption measurements were performed on 46 unique combinations
      of pollutants and sorbents with fOC values ranging from 0.001 to 0.150. Labile
      desorption rate constants indicate that release rates predominantly depend upon
      the fOC in the geosorbent. Previous theoretical models, such as the macro
      mesopore and organic matter (MOM) diffusion model, have predicted such a
      relationship but could not accurately predict the experimental rate constants
      collected in the present study. An empirical model was successfully developed to
      correlate the labile desorption rate constant (krap) to the fraction of organic
      material where log(krap)=0.291-0.785 . log(fOC). These results provide the first
      experimental evidence that kinetic pollution releases during resuspension events
      are governed by the fOC content in natural geosorbents.

PMID- 20821540
TI  - Spatial patterns of atmospherically deposited organic contaminants at high
      elevation in the southern Sierra Nevada mountains, California, USA.
AB  - Atmospherically deposited contaminants in the Sierra Nevada mountains of
      California, USA have been implicated as adversely affecting amphibians and fish,
      yet little is known about the distributions of contaminants within the mountains,
      particularly at high elevation. The hypothesis that contaminant concentrations in
      a high-elevation portion of the Sierra Nevada decrease with distance from the
      adjacent San Joaquin Valley was tested. Air, sediment, and tadpoles were sampled
      twice at 28 water bodies in 14 dispersed areas in Sequoia and Kings Canyon
      National Parks (2,785-3,375 m elevation; 43-82 km from Valley edge). Up to 15
      chemicals were detected frequently in sediment and tadpoles, including current-
      and historic-use pesticides, polychlorinated biphenyls, and polycyclic aromatic
      hydrocarbons. Only beta-endosulfan was found frequently in air. Concentrations of
      all chemicals detected were very low, averaging in the parts-per-billion range or
      less in sediment and tadpoles, and on the order of 10 pg/m3 for beta-endosulfan
      in air. Principal components analysis indicated that chemical compositions were
      generally similar among sites, suggesting that chemical transport patterns were
      likewise similar among sites. In contrast, transport processes did not appear to
      strongly influence concentration differences among sites, because variation in
      concentrations among nearby sites was high relative to sites far from each other.
      Moreover, a general relationship for concentrations as a function of distance
      from the valley was not evident across chemical, medium, and time. Nevertheless,
      concentrations for some chemical/medium/time combinations showed significant
      negative relationships with metrics for distance from the Valley. However, the
      magnitude of these distance effects among high-elevation sites was small relative
      to differences found in other studies between the valley edge and the nearest
      high-elevation sites.

PMID- 20821541
TI  - Toxic hazard of leachates from furfurylated wood: comparison between two
      different aquatic organisms.
AB  - Environmental concern regarding the use of toxic preservatives such as chromated
      copper arsenate (CCA) has been put forward. In the European Union, United States,
      and Japan, CCA has been phased out for residential and water-contact
      applications. Ecotoxicological studies of wood treated with conventional
      preservatives were carried out in the late 1990s, and it was concluded that the
      main impact is to water and aquatic organisms. Today, alternatives to
      conventional preservation methods, marketed as "environmentally friendly" or
      "nontoxic," are emerging. Examples of such alternatives are modified wood, e.g.,
      thermally modified, furfurylated, and acetylated wood. To date, not enough hazard
      characterization has been performed. In the present study, the Microtox assay
      with the marine bacterium Vibrio fischeri and the Daphtox procedure with the
      crustacean Daphnia magna were used as screening methods in an effect assessment.
      Both organisms were exposed to water leachates from furfurylated wood using two
      different leaching procedures. The results indicate that Microtox is more
      sensitive to the toxic components from furfurylated wood than Daphtox.
      Furthermore, the toxicity of treated Pinus radiata was higher than that of
      treated Pinus sylvestris. The toxicity did not diminish over the test period, as
      is the case for preservative-treated wood. The present study found that treatment
      conditions can influence the toxicity considerably, so toxicity studies should be
      included in the development of new treatment process. The present study also
      shows that using an intermediate vacuum-drying step, leading to a more efficient
      curing/polymerization, results in slightly less hydrophobic oligomers in the
      product, such that the leachates become less toxic to bacteria.

PMID- 20821542
TI  - Analysis of fullerene-C60 and kinetic measurements for its accumulation and
      depuration in Daphnia magna.
AB  - A simple method for analyzing masses of water suspended fullerenes (nC60) in
      Daphnia magna by extracting to toluene and measuring by ultraviolet-vis
      spectrophotometry was developed. This method was used to assess bioaccumulation
      and depuration rates by daphnia after nC60 exposure in artificial freshwater.
      Accumulation was rapid during the first few hours, and based on accumulation
      modeling, 90% of the steady-state concentration was reached in 21 h. After
      exposure for 24 h to a 2 mg/L fullerene solution, the daphnia accumulated 4.5+/
      0.7 g/kg wet weight, or 0.45% of the organism wet mass. Daphnids exposed to 2
      mg/L fullerenes for 24 h eliminated 46 and 74% of the accumulated fullerenes
      after depuration in clean water for 24 and 48 h, respectively. Transmission
      electron microscopy revealed that the majority of the fullerenes present in the
      gut of daphnids were large agglomerates. The significant fullerene uptake and
      relatively slow depuration suggest that D. magna may play a role as a carrier of
      fullerene from one trophic level to another. Additionally, D. magna may impact
      the fate of suspended fullerene particles in aquatic ecosystems by their ability
      to pack fullerene agglomerates into larger particles than were found in the
      exposure water, and then excrete agglomerates that are not stable in water,
      causing them to settle out of solution. This process decreases fullerene exposure
      to other aquatic organisms in the water column but may increase exposure to
      benthic organisms in the sediment.

PMID- 20821543
TI  - Intraperitoneal injections as a possible means of generating varied levels of
      methylmercury in the eggs of birds in field studies.
AB  - The ideal study of the effects of methylmercury on the reproductive success of a
      species of bird would be one in which eggs contained mercury concentrations
      ranging from controls to very heavily contaminated, all at the same site. Such a
      study cannot be realized at a Hg-contaminated area or under laboratory conditions
      but could be achieved by introducing methylmercury into breeding females and
      allowing them to deposit Hg in their eggs. Female mallards (Anas platyrhynchos)
      were intraperitoneally injected with solutions of methylmercury chloride
      dissolved in corn oil, propylene glycol, dimethyl sulfoxide, mineral oil,
      Olestra, Crisco, lard, hard paraffin, and a combination of hard and soft
      paraffin. In some cases, egg laying was delayed, as a result of either the
      solvent itself (in the case of Olestra, Crisco, and lard) or the highest
      concentration of methylmercury chloride (500 microg/g) in some of the solvents.
      Mercury in eggs ranged from a control level (<0.1 microg/g) to approximately 14
      microg/g on a wet weight basis, which more than covers the range of
      concentrations reported in wild bird eggs. Mercury concentrations in a series of
      eggs from the same female declined mostly as a result of excretion of Hg in prior
      eggs and not because of the length of time since the injection. Intraperitoneal
      injections hold promise in field studies in which one would like to study the
      reproductive effects of a wide range of methylmercury levels in the eggs of a
      wild bird and under the natural conditions that exist in the field.

PMID- 20821544
TI  - Influence of soil type and organic matter content on the bioavailability,
      accumulation, and toxicity of alpha-cypermethrin in the springtail Folsomia
      candida.
AB  - The influence of organic matter (OM) content on alpha-cypermethrin porewater
      concentrations and springtail Folsomia candida accumulation was investigated in
      two soils with different levels of organic matter, a forest soil with a total
      organic carbon (TOC) content of 5.0% (OM=11.5%) and an agricultural soil with a
      TOC content of 1.3% (OM=4.0%). Also, the effects of alpha-cypermethrin
      concentrations in soil and pore water and the influence of soil aging on
      springtail reproduction were investigated. Springtail reproduction was severely
      affected by increasing alpha-cypermethrin in soil with 1.3% TOC; the median
      effective concentration value (EC50) was estimated to 23.4 mg/kg (dry wt).
      Reproduction was only marginally affected in the soil with 5.0% TOC, and no EC50
      value could be estimated. However, when expressing alpha-cypermethrin
      accumulation as a function of soil alpha-cypermethrin concentrations, no
      difference was found between the two soil types, and no additional alpha
      cypermethrin uptake was observed at soil concentrations above approximately 200
      mg/kg (dry wt). By using solid-phase microextraction (SPME), it could be
      demonstrated that alpha-cypermethrin porewater concentrations were higher in the
      soil with low organic matter (LOM) content than in the soil with high organic
      matter (HOM) content. Furthermore, a clear relationship was found between alpha
      cypermethrin concentrations in springtails and porewater. Soil aging was not
      found to exert any effect on alpha-cypermethrin toxicity toward springtails. The
      study indicates that the springtail's accumulation of alpha-cypermethrin and
      reproduction is governed by alpha-cypermethrin porewater concentrations rather
      than the total alpha-cypermethrin concentration in soil.

PMID- 20821545
TI  - Effects of 17 beta-estradiol exposure on Xenopus laevis gonadal histopathology.
AB  - The natural estrogen 17 beta-estradiol (E2) is a potential environmental
      contaminant commonly employed as a positive control substance in bioassays
      involving estrogenic effects. The aquatic anuran Xenopus laevis is a frequent
      subject of reproductive endocrine disruptor research; however, histopathological
      investigations have tended to be less than comprehensive. Consequently, a study
      was designed to characterize gross and microscopic changes in the gonads of X.
      laevis as a result of E2 exposure. Additional goals of this study, which
      consisted of three separate experiments, included the standardization of
      diagnostic terminology and criteria, the validation of statistical methodology,
      and the establishment of a half maximal effective concentration (EC50) for E2 as
      defined by an approximately 50% conversion of presumptive genotypic males to
      phenotypic females. In the first experiment, frogs were exposed to nominal
      concentrations of 0, 0.2, 1.5, or 6.0 microg/L E2. From these experimental
      results and those of a subsequent range finding trial, the EC50 for E2 was
      determined to be approximately 0.2 microg/L. This E2 concentration was utilized
      in the other two experiments, which were performed at different facilities to
      confirm the reproducibility of results. Experiments were conducted according to
      Good Laboratory Practice guidelines, and the histopathologic evaluations were
      peer reviewed by an independent pathologist. Among the three trials, the
      histopathological findings that were strongly associated with E2-exposure
      (p<0.001 to 0.0001) included an increase in the proportion of phenotypic females,
      mixed sex, dilated testis tubules, dividing gonocytes in the testis, and dilated
      ovarian cavities in phenotypic ovaries. A comparison of the gross and microscopic
      evaluations suggested that some morphologic changes in the gonads may potentially
      be missed if studies rely entirely on macroscopic assessment.

PMID- 20821546
TI  - Relevance of octanol-water distribution measurements to the potential ecological
      uptake of multi-walled carbon nanotubes.
AB  - Many potential applications of carbon nanotubes (CNTs) require various
      physicochemical modifications prior to use, suggesting that nanotubes having
      varied properties may pose risks in ecosystems. A means for estimating
      bioaccumulation potentials of variously modified CNTs for incorporation in
      predictive fate models would be highly valuable. An approach commonly used for
      sparingly soluble organic contaminants, and previously suggested for use as well
      with carbonaceous nanomaterials, involves measurement of their octanol-water
      partitioning coefficient (KOW) values. To test the applicability of this
      approach, a methodology was developed to measure apparent octanol-water
      distribution behaviors for purified multi-walled carbon nanotubes and those acid
      treated. Substantial differences in apparent distribution coefficients between
      the two types of CNTs were observed, but these differences did not influence
      accumulation by either earthworms (Eisenia foetida) or oligochaetes (Lumbriculus
      variegatus), both of which showed minimal nanotube uptake for both types of
      nanotubes. The results suggest that traditional distribution behavior-based KOW
      approaches are likely not appropriate for predicting CNT bioaccumulation.

PMID- 20821547
TI  - Alarm substance recognition and predator avoidance by chinook salmon
      (Oncorhynchus tschawytscha) following exposure to an organophosphate pesticide.
AB  - The sense of smell in fish is thought to be important for behaviors associated
      with alarm scent recognition and predator avoidance. Olfactory function of
      juvenile chinook salmon was evaluated in two separate experiments following 2-h
      immersion exposures to 0, 1, 10, or 100 microg diazinon/L. In the first test
      system, groups of 10 salmon were transferred to the prechoice zone of a Y-maze
      fluviarium with parallel streams of water. A dilute alarm scent composed of
      either chinook skin extract or L-serine was pumped into the water supply of one
      arm. Fish were allowed to choose either upstream arm by raising a containment
      screen for 10 min, then their positions were photographed and the screen lowered.
      In the second test system the relationship of diazinon exposure to predation
      susceptibility was directly examined by transferring groups of 20 salmon (10
      diazinon-exposed, 10 control) to troughs containing a protective cover. These
      salmon were given two olfactory warnings by delivering conspecific skin extract
      to both their transfer container and the predation tank they entered. After a 2
      min prey acclimation period, larger predator rainbow trout were allowed access to
      the downstream section of the tank containing the test salmon. The combined fish
      were observed until approximately 50% of the prey fish had been consumed.
      Statistical comparisons indicated that although the salmon did avoid the water
      streams containing alarm scents, none of the diazinon exposure levels resulted in
      significantly different outcomes from the controls (alpha=0.05) in either the two
      choice maze study or the predation study. Possible environmental and population
      implications are discussed in light of related olfaction and diazinon studies.

PMID- 20821548
TI  - Chronic toxicity of fluorotelomer acids to Daphnia magna and Chironomus dilutus.
AB  - Saturated and unsaturated fluorotelomer carboxylic acids (fluorotelomer acids:
      FTAs) represent important intermediates in the degradation of fluorotelomer
      alcohols to perfluorinated carboxylic acids (PFCAs). Recent studies have detected
      FTAs at low concentrations (ng/L) in precipitation and surface waters; however,
      information regarding chronic toxicity is lacking. The present study assessed the
      chronic toxicity of the 8:2 saturated fluorotelomer carboxylic acid (8:2 FTCA) to
      Chironomus dilutus and the 10:2 saturated and unsaturated fluorotelomer
      carboxylic acids (10:2 FTCA and 10:2 fluorotelomer unsaturated carboxylic acid
      [FTuCA]) to Daphnia magna in separate life-cycle tests. In D. magna tests the
      FTCA was consistently more toxic than the FTuCA. Lethal concentrations (LC50s)
      were 150 and >60 microg/L for FTuCA and FTCA, respectively. Reproduction was
      significantly reduced relative to the controls, with respective median effective
      concentrations (EC50s) for time to first brood and mean number of
      offspring/female of 287 and 214 microg/L for FTuCA and 50 and 48 microg/L for
      FTCA. In tests with C. dilutus, EC50s for survival and growth at 20 d were 2,610
      and 1,250 microg/L. Total emergence and time to first emergence, the most
      sensitive endpoints, yielded EC50s of 440 and 890 microg/L. Few adults emerged
      and no reproduction occurred at the two highest concentrations (600 and 1540
      microg/L). Mean number of eggs/female was not affected. These results represent
      the first chronic toxicity data for FTCAs and additional evidence that FTCAs are
      more toxic than some PFCAs. While the results indicate that current environmental
      concentrations of FTAs likely pose negligible risk to aquatic biota, additional
      quantification of FTAs in surface waters and assessment of their toxicity is
      needed before meaningful assessments of potential risks to aquatic biota are
      possible.

PMID- 20821549
TI  - Heavy metals, hematology, plasma chemistry, and parasites in adult hellbenders
      (Cryptobranchus alleganiensis).
AB  - Ozark (Cryptobranchus alleganiensis bishopi) and eastern hellbenders (C. a.
      alleganiensis) from seven rivers in Missouri, USA, were collected to investigate
      essential information on hematology, parasites, and plasma chemistry and levels
      of select heavy metals (Hg, Pb, Cd, Cr, and Co) in the animals' blood. The body
      masses of Ozark hellbenders were much smaller than those of eastern hellbenders.
      Blood parasites were detected in Ozark hellbenders, but not eastern hellbenders.
      The higher frequency in occurrence of eosinophils in Ozark hellbenders (8.8
      16.8%) than in eastern hellbenders (highest at 6.6%) might result from the
      infection of parasites. Seven of the 18 hematology and plasma parameters
      (hematocrit, basophils, eosinophils, K, P, Ca, and chloride) showed significant
      differences between subspecies. The blood levels of heavy metals Co, Hg, and Pb
      differed significantly between subspecies. Ozark hellbenders had higher blood
      levels of Co (p<0.001), while blood levels of Hg and Pb were higher in eastern
      hellbenders. The levels of chromium (Cr) and cadmium (Cd) were not different
      between subspecies and among rivers. The eastern hellbenders at Niangua River and
      the Ozark hellbenders at the North Fork of the White River had lower Hg levels
      compared to eastern and Ozark hellbenders at other sites. All together, our
      findings provide important baseline information for managing this endangered
      species.

PMID- 20821550
TI  - Cytochrome P4501A biomarker indication of oil exposure in harlequin ducks up to
      20 years after the Exxon Valdez oil spill.
AB  - Hydrocarbon-inducible cytochrome P4501A (CYP1A) expression was measured, as
      ethoxyresorufin-O-deethylase (EROD) activity, in livers of wintering harlequin
      ducks (Histrionicus histrionicus) captured in areas of Prince William Sound,
      Alaska, USA, oiled by the 1989 Exxon Valdez spill and in birds from nearby
      unoiled areas, during 2005 to 2009 (up to 20 years following the spill). The
      present work repeated studies conducted in 1998 that demonstrated that in
      harlequin ducks using areas that received Exxon Valdez oil, EROD activity was
      elevated nearly a decade after the spill. The present findings strongly supported
      the conclusion that average levels of hepatic EROD activity were higher in ducks
      from oiled areas than those from unoiled areas during 2005 to 2009. This result
      was consistent across four sampling periods; furthermore, results generated from
      two independent laboratories using paired liver samples from one of the sampling
      periods were similar. The EROD activity did not vary in relation to age, sex, or
      body mass of individuals, nor did it vary strongly by season in birds collected
      early and late in the winter of 2006 to 2007, indicating that these factors did
      not confound inferences about observed differences between oiled and unoiled
      areas. We interpret these results to indicate that harlequin ducks continued to
      be exposed to residual Exxon Valdez oil up to 20 years after the original spill.
      This adds to a growing body of literature suggesting that oil spills have the
      potential to affect wildlife for much longer time frames than previously assumed.

PMID- 20821551
TI  - Toxicity and biotransformation of uncoated and coated nickel hydroxide
      nanoparticles on mesquite plants.
AB  - Nanomaterials are of particular interest in environmental chemistry due to their
      unknown toxicity to living organisms. Reports indicate that nanoparticles (NPs)
      affect seed germination, but the uptake and biotransformation of metal
      nanoparticles is not well understood. The present study investigated the toxicity
      and biotransformation of Ni(OH)2 NPs by mesquite plants (Prosopis sp.). Three
      sets of plants were treated for four weeks with 0.01, 0.05, or 0.10 g of either
      uncoated or sodium citrate coated NPs before and after synthesis. Nickel
      concentrations in plants were determined by inductively coupled plasma-optical
      emission spectroscopy (ICP-OES) and the form and oxidation state of Ni was
      determined using X-ray absorption spectroscopy (XAS). Results showed that
      uncoated NPs had an average size of 8.7 nm, whereas coated NPs before and after
      synthesis had an average of 2.5 and 0.9 nm, respectively. The ICP-OES results
      showed that plants treated with 0.10 g of uncoated and coated NPs before and
      after synthesis had 803, 764, and 400 mg Ni kg dry weight, in the leaves,
      respectively. The XAS analyses showed Ni NPs in roots and shoots of plants
      treated with uncoated NPs, whereas leaves showed a Ni(II)-organic acid type
      complex. However, plants treated with coated NPs before or after synthesis showed
      Ni NPs only in roots and a Ni(II)-organic acid complex in shoots and leaves.
      Results also showed that none of the treatments reduced plant size or chlorophyll
      production. To the authors' knowledge, this is the first time that the
      biotransformation of nanoparticles by a plant system is reported.

PMID- 20821552
TI  - Relationship between laying sequence and mercury concentration in tree swallow
      eggs.
AB  - When female birds lay eggs, some of their body burden of mercury is eliminated
      into each egg, potentially leading to declining mercury across the clutch.
      However, there was no decline in mercury with laying sequence in clutches of tree
      swallow (Tachycineta bicolor) eggs at a mercury-contaminated site, presumably due
      to daily replenishment of mercury in females during laying. Sampling just one egg
      from the nest provided an accurate measure of clutch mercury contamination.

PMID- 20821553
TI  - Toxicity of dispersed weathered crude oil to early life stages of Atlantic
      herring (Clupea harengus).
AB  - Reports of the chronic toxicity of dispersed crude oil to early life stages of
      fish perpetuate uncertainty about dispersant use. However, realistic exposures to
      dispersed oil in the water column are thought to be much briefer than exposures
      associated with chronic toxicity testing. To address this issue, the toxicity of
      dispersed weathered oil to early life stages of Atlantic herring (Clupea
      harengus) was tested for short exposure durations, ranging from 1 to 144 h.
      Toxicity was a function of concentration and duration of exposure, as well as of
      the life stage exposed. Medium South American crude oil dispersed with Corexit
      9500 caused blue sac disease in embryos, but not in free-swimming embryos. The
      age of embryos was negatively correlated with their sensitivity to oil; those
      freshly fertilized were most sensitive. Sensitivity increased after hatch, with
      free-swimming embryos showing signs of narcosis. Gametes were also tested;
      dispersed oil dramatically impaired fertilization success. For exposures of less
      than 24 h, gametes and free-swimming embryos were the most sensitive life stages.
      For those of more than 24 h, young embryos (<1 d old) were most sensitive. The
      results are presented as statistical models that could assist decisions about
      dispersant use in the vicinity of fish spawning habitats.

PMID- 20821554
TI  - Comparing weighted and unweighted analyses applied to data with a mix of pooled
      and individual observations.
AB  - Smaller organisms may have too little tissue to allow assaying as individuals. To
      get a sufficient sample for assaying, a collection of smaller individual
      organisms is pooled together to produce a simple observation for modeling and
      analysis. When a dataset contains a mix of pooled and individual organisms, the
      variances of the observations are not equal. An unweighted regression method is
      no longer appropriate because it assumes equal precision among the observations.
      A weighted regression method is more appropriate and yields more precise
      estimates because it incorporates a weight to the pooled observations. To
      demonstrate the benefits of using a weighted analysis when some observations are
      pooled, the bias and confidence interval (CI) properties were compared using an
      ordinary least squares and a weighted least squares t-based confidence interval.
      The slope and intercept estimates were unbiased for both weighted and unweighted
      analyses. While CIs for the slope and intercept achieved nominal coverage, the CI
      lengths were smaller using a weighted analysis instead of an unweighted analysis,
      implying that a weighted analysis will yield greater precision.

PMID- 20821555
TI  - Site-specific probabilistic ecological risk assessment of a volatile chlorinated
      hydrocarbon-contaminated tidal estuary.
AB  - Groundwater contaminated with volatile chlorinated hydrocarbons (VCHs) was
      identified as discharging to Penrhyn Estuary, an intertidal embayment of Botany
      Bay, New South Wales, Australia. A screening-level hazard assessment of surface
      water in Penrhyn Estuary identified an unacceptable hazard to marine organisms
      posed by VCHs. Given the limitations of hazard assessments, the present study
      conducted a higher-tier, quantitative probabilistic risk assessment using the
      joint probability curve (JPC) method that accounted for variability in exposure
      and toxicity profiles to quantify risk (delta). Risk was assessed for 24
      scenarios, including four areas of the estuary based on three exposure scenarios
      (low tide, high tide, and both low and high tides) and two toxicity scenarios
      (chronic no-observed-effect concentrations [NOEC] and 50% effect concentrations
      [EC50]). Risk (delta) was greater at low tide than at high tide and varied
      throughout the tidal cycle. Spatial distributions of risk in the estuary were
      similar using both NOEC and EC50 data. The exposure scenario including data
      combined from both tides was considered the most accurate representation of the
      ecological risk in the estuary. When assessing risk using data across both tides,
      the greatest risk was identified in the Springvale tributary (delta=25%)-closest
      to the source area-followed by the inner estuary (delta=4%) and the Floodvale
      tributary (delta=2%), with the lowest risk in the outer estuary (delta=0.1%),
      farthest from the source area. Going from the screening level ecological risk
      assessment (ERA) to the probabilistic ERA changed the risk from unacceptable to
      acceptable in 50% of exposure scenarios in two of the four areas within the
      estuary. The probabilistic ERA provided a more realistic assessment of risk than
      the screening-level hazard assessment.

PMID- 20821556
TI  - Similarity, independence, or interaction for binary mixture effects of nerve
      toxicants for the nematode Caenorhabditis elegans.
AB  - Intensive agriculture can require the simultaneous use of more than one
      pesticide, resulting in the presence of mixtures in soils and waters. To assess
      mixture effects, concentration addition (CA) for similar acting chemicals and
      independent action (IA) for dissimilar acting chemicals are the most frequently
      used models. While the mechanistic basis for the selection of CA and IA for a
      given mixture appears appealing (similar vs dissimilar action), it has not yet
      been established how similar chemicals need to be in their effect before CA
      should be viewed as the most appropriate model. Here this is investigated in
      studies of the toxicity of binary mixtures of five different pesticides from
      three classes that have the same putative mode of action (neuroexcitation) but
      different molecular mechanisms in binary mixture tests with the nematode
      Caenorhabditis elegans. Effects of exposure on nematode survival were limited at
      the concentrations tested. Data analysis, therefore, focused on reproductive
      toxicity. Both CA and IA were found to be valid models for prediction of the
      toxicity of the 10 mixtures, although for seven CA provided a mathematically
      better fit. Both models could describe the toxicity for four mixtures; however,
      evidence for interaction was found in the remaining six cases. Where interactions
      occurred, these could be explained by information on the potential mechanisms of
      compound toxicokinetics-particularly when mixtures comprised a metabolically
      activated and a metabolically deactivated chemical and/or cases where the
      relative potencies of the two tested chemicals differed greatly. It is concluded,
      therefore, that detailed analysis of toxicokinetics and toxicodynamics can aid
      further understanding of interactions in mixtures.

PMID- 20821557
TI  - Assessment criteria for using the sea-urchin embryo test with sediment elutriates
      as a tool to classify the ecotoxicological status of marine water bodies.
AB  - A large, multiyear data set was generated by pooling the sediment elutriate (SET)
      results collected during previous studies conducted in the Galician Rias
      (northwest Iberian Peninsula) that met the acceptability criteria in the
      controls, to ensure optimum quality of data (n=162). Two subsets of equal to
      reference and lower than reference sites were identified by comparing the
      Percentage Net Response (PNR) value from each sampling site with nontoxic, cruise
      specific, reference sites by using the t test with the unequal variance
      assumption. Ecotoxicological Assessment Criteria (EAC0, EAC1, EAC2, and EAC3)
      were then derived from those two subsets to classify the SET results into five
      categories of ecotoxicological status: high, good, moderate, poor, and bad, in
      line with the European legislation. The 50th and 5th percentiles of the PNR
      distribution of the equal to reference sites subset were EAC0=0.879 and
      EAC1=0.694. An EAC2=0.508 was obtained from the 50th percentile of the lower than
      reference sites subset. Because the PNR values of the entire database showed a
      distribution that can be adjusted to two normal populations, the EAC3=0.240 PNR
      was calculated as the intersection between the first and second normal
      distributions identified. Power analysis proved that the limit between acceptable
      and unacceptable status (EAC1) corresponded to a detectable PNR difference to
      control with a confidence level>99% and a power of 95%.

PMID- 20821559
TI  - Determination of the cultivar and aging of Sicilian olive oils using HPLC-MS and
      linear discriminant analysis.
AB  - A large number of certified samples (84) of Sicilian olive oils arising from the
      eight cultivars most represented in Sicily (Biancolilla, Cerasuola, Moresca,
      Nocellara del Belice, Nocellara Etnea, Oglialora Messinese, Brandofino and Tonda
      Iblea) have been collected and analyzed by HPLC/MS using an atmospheric pressure
      chemical ionization (APCI) source. The sample preparation is very simple; in
      fact, the oil samples are diluted without any chemical derivatization. A
      following statistical data treatment by general discriminant analysis (GDA)
      allows the determination of the olive oil cultivar. Furthermore, changes in the
      composition of glyceridic components of the olive oils lead to easy
      discrimination between fresh oils and 1-year-old samples.

PMID- 20821560
TI  - Urban pesticide risk assessment and risk management: get involved.

PMID- 20821561
TI  - Wash-off potential of urban use insecticides on concrete surfaces.
AB  - Contamination of surface aquatic systems by insecticides is an emerging concern
      in urban watersheds, but sources of contamination are poorly understood,
      hindering development of regulatory or mitigation strategies. Hardscapes such as
      concrete surfaces are considered an important facilitator for pesticide runoff
      following applications around homes. However, pesticide behavior on concrete has
      seldom been studied, and standardized evaluation methods are nonexistent. In the
      present study, a simple batch method for measuring pesticide wash-off potential
      from concrete surfaces was developed, and the dependence of washable pesticide
      residues was evaluated on pesticide types, formulations, time exposed to outdoor
      conditions, and number of washing cycles. After application to concrete, the
      washable fraction of four pyrethroids (bifenthrin, permethrin, cyfluthrin, and
      cyhalothrin) and fipronil rapidly decreased, with half-lives < or =3 d, likely
      due to irreversible retention in micropores below the concrete surface. The
      initial fast decrease was followed by a much slower declining phase with half
      lives ranging from one week to two months, and detectable residues were still
      found in the wash-off solution for most treatments after 112 d. The slow decrease
      may be attributed to a fraction of pesticides being isolated from degradation or
      volatilization after retention below the concrete surface. Wash-off potential was
      consistently higher for solid formulations than for liquid formulations, implying
      an increased runoff contamination risk for granular and powder formulations.
      Trace levels of pyrethroids were detected in the wash-off solution even after 14
      washing-drying cycles over 42 d under outdoor conditions. Results from the
      present study suggest that pesticide residues remain on concrete and are
      available for contaminating runoff for a prolonged time. Mechanisms for the long
      persistence were not clearly known from the present study and merit further
      investigation.

PMID- 20821562
TI  - Pesticide transport with runoff from creeping bentgrass turf: Relationship of
      pesticide properties to mass transport.
AB  - The off-site transport of pesticides with runoff is both an agronomic and
      environmental concern, resulting from reduced control of target pests in the area
      of application and contamination of surrounding ecosystems. Experiments were
      designed to measure the quantity of pesticides in runoff from creeping bentgrass
      (Agrostis palustris) turf managed as golf course fairway to gain a better
      understanding of factors that influence chemical availability and mass transport.
      Less than 1 to 23% of applied chloropyrifos, flutolanil, mecoprop-p (MCPP),
      dimethylamine salt of 2,4-dichlorophenoxyacetic acid (2,4-D), or dicamba was
      measured in edge-of-plot runoff when commercially available pesticide
      formulations were applied at label rates 23 +/- 9 h prior to simulated
      precipitation (62 +/- 13 mm). Time differential between hollow tine core
      cultivation and runoff did not significantly influence runoff volumes or the
      percentage of applied chemicals transported in the runoff. With the exception of
      chlorpyrifos, all chemicals of interest were detected in the initial runoff
      samples and throughout the runoff events. Chemographs of the five pesticides
      followed trends in agreement with mobility classifications associated with their
      soil organic carbon partition coefficient (K(OC).) Data collected from the
      present study provides information on the transport of chemicals with runoff from
      turf, which can be used in model simulations to predict nonpoint source pollution
      potentials and estimate ecological risks.

PMID- 20821563
TI  - Evaluation of core cultivation practices to reduce ecological risk of pesticides
      in runoff from Agrostis palustris.
AB  - Pesticides associated with the turfgrass industry have been detected in storm
      runoff and surface waters of urban watersheds, invoking concern of their
      potential environmental effects and a desire to reduce their transport to
      nontarget locations. Quantities of chlorpyrifos, dicamba, dimethylamine salt of
      2,4-dichlorophenoxyacetic acid (2,4-D), flutolanil, and mecoprop-p (MCPP)
      transported in runoff from bentgrass (Agrostis palustris) fairway turf managed
      with solid tine (ST) or hollow tine (HT) core cultivation were compared to
      determine which cultivation practice is more efficient at mitigating
      environmental risk. Plots receiving HT core cultivation showed a 10 and 55%
      reduction in runoff volume and a 15 to 57% reduction in pesticide transport with
      runoff at 63 d and 2 d following core cultivation. Estimated environmental
      concentrations of the pesticides in a surface water receiving runoff from turf
      managed with ST core cultivation exceeded the median lethal concentration (LC50)
      or median effective concentration (EC50) of nine aquatic organisms evaluated.
      Replacing ST core cultivation with HT core cultivation reduced surface water
      concentrations of the pesticides to levels below the LC50 and EC50 for most these
      aquatic organisms, lessening risk associated with pesticides in runoff from the
      fairway turf. Results of the present research provide quantitative information
      that will allow for informed decisions on cultural practices that can maximize
      pesticide retention at the site of application, improving pest control in turf
      while minimizing environmental contamination and adverse effects associated with
      the off-site transport of pesticides.

PMID- 20821564
TI  - Quantitative analysis of over 20 years of golf course monitoring studies.
AB  - The purpose of the present study was to comprehensively evaluate available golf
      course water quality data and assess the extent of impacts, as determined by
      comparisons with toxicologic and ecologic reference points. Most water quality
      monitoring studies for pesticides have focused on agriculture and often the
      legacy chemicals. There has been increased focus on turf pesticides since the
      early 1990s, due to the intense public scrutiny proposed golf courses receive
      during the local permitting process, as well as pesticide registration
      evaluations by the U.S. Environmental Protection Agency under the Federal
      Insecticide, Fungicide, and Rodenticide Act (FIFRA). Results from permit-driven
      studies are frequently not published and knowledge about them is usually not
      widespread. Forty-four studies involving 80 courses from a 20-year period passed
      our quality control and other review criteria. A total of 38,827 data entries
      (where one analysis for one substance in one sample equals a data entry) from
      pesticide, pesticide metabolite, total phosphorus, and nitrate analyses of
      surface water and groundwater were evaluated. Analytes included 161 turf-related
      pesticides and pesticide metabolites. Widespread and/or repeated water quality
      impacts by golf courses had not occurred at the sites studied, although concerns
      are raised herein about phosphorus. Individual pesticide database entries that
      exceed toxicity reference points for groundwater and surface water are 0.15 and
      0.56%, respectively. These percentages would be higher if they could be expressed
      in terms of samples collected rather than chemicals analyzed. The maximum
      contaminant level ([MCL]; 10 mg/L) for nitrate-nitrogen was exceeded in 16/1,683
      (0.95%) of the groundwater samples. There were 1,236 exceedances of the total
      phosphorus ecoregional criteria in five ecoregions for 1,429 (86.5%) data
      entries. (This comparison is conservative because many of the results in the
      database are derived from storm flow events.) Thus, phosphorus appears to present
      the greatest water quality problem in these studies. Pesticides detected in wells
      had longer soil metabolism half-lives (49 d) compared with those not detected (22
      d), although the means were not significantly different.

PMID- 20821566
TI  - Impacts of crab bioturbation on the fate of polycyclic aromatic hydrocarbons in
      sediment from the Beitang estuary of Tianjin, China.
AB  - Bioturbation by the burrowing crab Helice tiensinensis was investigated to
      determine its impact on polycyclic aromatic hydrocarbon (PAH)-contaminated
      estuarine sediments. The concentrations of 16 U.S. Environmental Protection
      Agency (U.S. EPA) priority PAHs in sediment and pore water from a crab bed
      (including surface and burrow samples) and a control area, as well as in crabs,
      were measured. The total concentration of the 16 U.S. EPA priority PAHs in
      surface sediment of the crab bed (average 2,772 ng/g dry weight) was
      significantly higher than in the control area (1,173 ng/g dry weight). In the
      crab bed, the total concentration of PAHs in burrow sediment (1,239 ng/g dry
      weight) was lower than in surface sediment, and a similar trend was found for
      most of the individual PAHs, except for indeno[1,2,3-cd]pyrene, and
      benzo[ghi]perylene. The enhanced PAH desorption in the burrow, which could be
      attributed to the increase in dissolved organic matter in pore water as well as
      the mechanical mixing by the crab, is expected to increase PAH flux to the sea.
      In addition to increased flushing to the sea, incorporation of PAHs in crab
      biomass and metabolism of PAHs by the crab, stimulated microbial degradation, was
      proposed as an ignorable factor that lowered the PAH concentration in burrow
      sediment, because crab bioturbation increases the abundance and activity of
      microorganisms through several means. Log K(OW) and log K(OC) correlated well for
      individual PAHs in sediment in the control area, although this correlation was
      poor for sediments in the crab bed. The log biota-sediment accumulation factor
      (BSAF) of PAHs exhibited a negative relationship with log K(OW), suggesting that
      the bioaccumulation of sorbed PAHs was controlled primarily by their
      bioavailability.

PMID- 20821565
TI  - Environmental and human exposure to persistent halogenated compounds derived from
      e-waste in China.
AB  - Various classes of persistent halogenated compounds (PHCs) can be released into
      the environment due to improper handling and disposal of electronic waste (e
      waste), which creates severe environmental problems and poses hazards to human
      health as well. In this review, polybrominated diphenyl ethers (PBDEs),
      polybrominated biphenyls (PBBs), tetrabromobisphenol A (TBBPA), polybrominated
      phenols (PBPs), polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p
      dioxins and dibenzofurans (PCDD/Fs), polybrominated dibenzo-p-dioxins and
      dibenzofurans (PBDD/Fs), and chlorinated polycyclic aromatic hydrocarbons
      (ClPAHs) are the main target contaminants for examination. As the world's largest
      importer and recycler of e-waste, China has been under tremendous pressure to
      deal with this huge e-waste situation. This review assesses the magnitude of the
      e-waste problems in China based on data obtained from the last several years,
      during which many significant investigations have been conducted. Comparative
      analyses of the concentrations of several classes of toxic compounds, in which e
      waste recycling sites are compared with reference sites in China, have indicated
      that improper e-waste handling affects the environment of dismantling sites more
      than that of control sites. An assessment of the annual mass loadings of PBDEs,
      PBBs, TBBPA, PBPs, PCDD/Fs, and ClPAHs from e-waste in China has shown that PBDEs
      are the dominant components of PHCs in e-waste, followed by ClPAHs and PCDD/Fs.
      The annual loadings of PBDEs, ClPAHs, and PCDD/Fs emission were estimated to
      range from 76,200 to 182,000, 900 to 2,000 and 3 to 8 kg/year, respectively.
      However, PCDD/Fs and ClPAHs should not be neglected because they are also
      primarily released from e-waste recycling processes. Overall, the magnitude of
      human exposure to these toxics in e-waste sites in China is at the high end of
      the global range.

PMID- 20821567
TI  - Simplified sample preparation procedure for measuring isotope-enriched
      methylmercury by gas chromatography and inductively coupled plasma mass
      spectrometry.
AB  - Many procedures have been developed to measure the concentration of
      monomethylmercury (MeHg) from different sample matrices, and the use of stable
      isotopes of mercury now provides opportunities to determine its formation and
      degradation rates. Here, a modified procedure for measuring mercury isotopes in
      sediment samples that uses acid leaching-ion exchange-thiosulfate extraction
      (TSE) to isolate and purify the methylated mercury from the matrix is proposed.
      The latter is followed by aqueous-phase ethylation, purge and trap on Tenax, gas
      chromatography separation of ethylated mercury compounds, and inductively coupled
      plasma mass spectrometry detection. The new TSE procedure bridges together two
      well-known methods, the acid-leaching and distillation-derivatization procedures,
      offering the advantages of artifact-free formation of the first, and low
      detection limits and the possibility of quantification of individual isotopes of
      mercury of the second. The modified procedure retains the derivatization, purge
      and trap, and gas chromatography and inductively coupled plasma mass spectrometry
      (GC-ICP-MS) detection steps from the distillation-derivatization procedure, and
      eliminates the distillation step, which is not only laborious but also expensive,
      due to the high cost of installation and time-consuming cleaning process. Major
      advantages of the TSE procedure proposed include the extraction and analysis of a
      large number of samples in a short time, excellent analyte recoveries, and the
      lack of artifact formation. Sediment certified reference materials (CRMs), BCR
      580 and IAEA 405, were used to test the TSE procedure accuracy. Recoveries
      between 94 to 106% and 95 to 96% were obtained for CRMs and spiked samples (Milli
      Q(R) water), respectively. Comparisons among thiosulfate extraction,
      distillation, and acid-leaching procedures have shown good agreement of
      methylmercury values.

PMID- 20821568
TI  - Tissue-specific distribution and whole-body burden estimates of persistent
      organic pollutants in the bottlenose dolphin (Tursiops truncatus).
AB  - Most exposure assessments for free-ranging cetaceans focus on contaminant
      concentrations measured in blubber, and few data are available for other tissues
      or the factors governing contaminant distribution among tissues. The goal of this
      study was to provide a detailed description of the distribution of persistent
      organic pollutants (POPs) within the common bottlenose dolphin (Tursiops
      truncatus) body and assess the role of lipid dynamics in mediating contaminant
      distribution. Thirteen tissues (brain, blubber, heart, liver, lung, kidney,
      mammary gland, melon, skeletal muscle, spleen, thyroid, thymus, and
      testis/uterus) were sampled during necropsy from bottlenose dolphins (n = 4) and
      analyzed for lipid and 85 POPs, including polychlorinated biphenyls,
      organochlorine pesticides, and polybrominated diphenyl ethers. Significant
      correlations between tissue POP concentrations and lipid suggest that
      distribution of POPs is generally related to tissue lipid content. However,
      blubber:tissue partition coefficients ranged widely from 0.753 to 6.25,
      suggesting that contaminant distribution is not entirely lipid-dependent. Tissue
      specific and whole-body contaminant burdens confirmed that blubber, the primary
      site of metabolic lipid storage, is also the primary site for POP accumulation,
      contributing >90% to the whole-body burdens. Observations also suggest that as
      lipid mobilizes from blubber, contaminants may redistribute, leading to elevated
      tissue concentrations. These results suggest that individuals with reduced
      blubber lipid may be at increased risk for exposure-related health effects.
      However, this study also provides evidence that the melon, a metabolically inert
      lipid-rich structure, may serve as an alternate depot for POPs, thus preventing
      the bulk of blubber contaminants from being directly available to other tissues.
      This unique physiological adaptation should be taken into consideration when
      assessing contaminant-related health effects in wild cetacean populations.

PMID- 20821569
TI  - Toxicity of the molybdate anion in soil is partially explained by effects of the
      accompanying cation or by soil pH.
AB  - Previous studies have shown that toxicity of cationic trace metals in soil is
      partially confounded by effects of the accompanying anions. A similar assessment
      is reported here for toxicity of an oxyanion, i.e., molybdate (MoO(4) (2-)), the
      soil toxicity of which is relatively unexplored. Solubility and toxicity were
      compared between the soluble sodium molybdate (Na(2)MoO(4)) and the sparingly
      soluble molybdenum trioxide (MoO(3)). Confounding effects of salinity were
      excluded by referencing the Na(2)MoO(4) effect to that of sodium chloride (NaCl).
      The pH decrease from the acid MoO(3) amendment was equally referenced to a
      hydrochloric (HCl) treatment or a lime-controlled MoO(3) treatment. The
      concentrations of molybdenum (Mo) in soil solution or calcium chloride (CaCl(2))
      0.01 M extracts were only marginally affected by either MoO(3) or Na(2)MoO(4) as
      an Mo source after 10 to 13 days of equilibration. Effects of Mo on soil
      nitrification were fully confounded by associated changes in salinity or pH.
      Effects of Mo on growth of wheat seedlings (Triticum aestivum L) were more
      pronounced than those on nitrification, and toxicity thresholds were unaffected
      by the form of added Mo. The Mo thresholds for wheat growth were not confounded
      by pH or salinity at incipient toxicity. It is concluded that oxyanion toxicity
      might be confounded in relatively insensitive tests for which reference
      treatments should be included.

PMID- 20821570
TI  - Assessment of estrogenic activity conducted by combining bioassay and chemical
      analyses of the effluent from wastewater treatment plants in Nanjing, China.
AB  - The estrogenic activity of the effluent from three municipal wastewater treatment
      plants (WWTPs) in Nanjing, China, was investigated. The water samples were
      enriched by solid-phase extraction and then eluted with different polar solvents,
      which gave 11 fractionated extracts. Chemical analysis and a vitellogenin (Vtg)
      assay in goldfish (Carassias auratus) were then utilized to evaluate the
      estrogenic activities 7 d after a single injection of the effluent extracts of
      WWTPs and to identify causative agents that led to the induction of Vtg in male
      fish. The results reveal that Vtg induction occurred primarily in response to the
      75 to 90% methanol extracts, and different concentrations of the natural
      estrogens estrone (E(1)) and 17beta-estradiol (E(2)) were detected in these
      extracts. As the Vtg induction increased, the plasma E(2) levels increased, and a
      correlation between Vtg and E(2) does exist. Furthermore, the gonadal somatic
      index (GSI) did not decrease significantly (p > 0.05) when the Vtg concentrations
      were elevated after 7 d. Different concentrations of estrogens were detected in
      the effluents, which demonstrated that the current treatment processes employed
      by the three WWTPs could not fully remove these compounds. As a result, the
      aquatic organisms in the receiving water (Yangtze River) were at a risk of
      feminization.

PMID- 20821571
TI  - Triclosan has endocrine-disrupting effects in male western mosquitofish, Gambusia
      affinis.
AB  - Triclosan (TCS) is an antibacterial agent used in a variety of personal care and
      industrial products. Triclosan and its environmentally transformed derivative,
      methyl-TCS, have been detected in waters receiving effluent from public
      wastewater treatment plants. Previous studies have demonstrated that TCS has the
      potential to act as an endocrine disruptor. The present study tested the
      hypothesis that TCS acts as an endocrine-disrupting agent in fish. Mature male
      western mosquitofish, Gambusia affinis, were exposed to TCS concentrations of
      100, 200, and 350 nM (29.0, 57.9, and 101.3 microg/L) for 35 d by the static
      renewal method. Induction of the normally female-limited vitellogenin gene
      expression and reduction in sperm count were quantified as biomarkers of
      endocrine disruption. Vitellogenin mRNA expression was significantly elevated in
      the 350 nM TCS treatment. Sperm counts in the same treatment group were
      significantly decreased. The mean hepatosomatic index in the 350 nM treatment
      group was significantly increased. This study demonstrates that TCS has the
      potential to act as an endocrine disruptor in male mosquitofish.

PMID- 20821572
TI  - Population models in pesticide risk assessment: lessons for assessing population
      level effects, recovery, and alternative exposure scenarios from modeling a small
      mammal.
AB  - In the last few years, the interest in using ecological population models as a
      tool for pesticide risk assessment has increased rapidly. Practical guidance,
      however, on how to perform a risk assessment with a population model is still
      lacking. It is still unclear which endpoint (population density, population
      growth, etc.) is the most sensitive indicator of population-level effects and how
      risk can be evaluated at the population level. Moreover, a main added value of
      model-based risk assessments, which is an understanding of the mechanisms
      involved in alternative exposure scenarios, so far has received little attention.
      We therefore used an example model to compare commonly used endpoints and
      alternative exposure scenarios. The model is a structurally realistic, but
      relatively simple, individual-based, spatially explicit model for the common
      shrew (Sorex araneus), which was selected because it has been tested and
      validated extensively. We show that population density is more sensitive for
      detecting population-level effects in the short term (months) than population
      growth rate. Population viability measured by extinction risk can also be a
      relevant endpoint, because it is especially sensitive for small populations. We
      show that landscape structure and the timing of pesticide application (population
      structure at the time of application) can have a great impact on population
      recovery, and we analyze statistical tests for use in population-level risk
      assessments. Our results demonstrate which factors and insights should be taken
      into account in population-level risk assessments.

PMID- 20821573
TI  - Polyhalogenated aromatic hydrocarbons and metabolites: Relation to circulating
      thyroid hormone and retinol in nestling bald eagles (Haliaeetus leucocephalus).
AB  - Polyhalogenated aromatic hydrocarbons are global contaminants that are often
      considered to be endocrine disruptors and include 1,1-dichloro-2,2-bis(4
      chlorophenyl)ethylene (p,p'-DDE), polychlorinated biphenyls (PCBs), and
      polybrominated diphenyl ethers (PBDEs). The present study examined these
      compounds and their hydroxylated metabolites or analogues and relationships with
      circulating thyroid hormones and retinols in plasma from nestling and adult bald
      eagles in British Columbia, Canada, and California, USA. We also compared our
      results with published data. Thyroxine (T4) decreased with summation operatorPCB
      and CB153 in nestling bald eagles, which was congruent with results from nine of
      14 other published avian laboratory and field studies. Free thyroid hormone
      levels also decreased with CB-153 and hydroxylated PCBs (OH-PCBs). Retinol
      increased with CB118 and CB180 in nestling eagles, decreased with OH-PCBs in a
      subset of nestlings, and decreased in 7 of 12 PCB published studies. Thyroxine
      decreased with p,p'-DDE for nestlings and with data reported in one of five other
      published studies. In our samples, plasma retinol, triiodothyronine (T3), and T4
      were independent of summation operatorPBDEs, whereas summation operatorOH-PBDEs
      were weakly but significantly correlated with increases in T3 and retinol. Adult
      bald eagles showed no relationship between contaminants and thyroid hormones,
      which is consistent with other studies of long-lived birds, perhaps because adult
      birds have time to adjust to contaminant levels. Measurement of circulating
      thyroid hormones appears to be a more useful biomarker than retinols, given the
      more consistent response of T4 to PCBs here and reported in the literature. We
      conclude that current environmental exposures to PCBs in British Columbia and in
      southern California are associated with significant decreases in T4, suggesting a
      potential negative effect on the endocrine system of nestling bald eagles.

PMID- 20821574
TI  - Environmental occurrence and reproductive effects of the pharmaceutical
      fluoxetine in native freshwater mussels.
AB  - The present study measured the occurrence, distribution, and bioaccumulation of
      fluoxetine in samples of water, polar organic chemical integrative sampler
      (POCIS), sediment, and caged freshwater mussels at stream sites near a municipal
      wastewater treatment facility effluent discharge. We assessed the relation of the
      environmental concentrations to reproductive endpoints in mussels in acute
      laboratory tests. Concentrations of fluoxetine in water and POCIS samples were
      similar (<20% difference) within each site and were greatest in the effluent
      channel (104-119 ng/L), and decreased at 50 m and 100 m downstream. Likewise,
      concentrations of fluoxetine in sediment and mussel (Elliptio complanata) tissue
      were greatest in the effluent channel (17.4 ng/g wet wt for sediment and 79.1
      ng/g wet wt for mussels). In 96-h lab tests, fluoxetine significantly induced
      parturition of nonviable larvae from female E. complanata exposed to 300 microg/L
      (p = 0.0118) and 3,000 microg/L (p < 0.0001) compared to controls. Fluoxetine
      exposure at 300 microg/L (p = 0.0075) and 3,000 microg/L (p = 0.0001) also
      resulted in stimulation of lure display behavior in female Lampsilis fasciola and
      Lampsilis cardium, respectively. In male E. complanata, 3,000 microg fluoxetine/L
      significantly induced release of spermatozeugmata during a 48-h exposure. These
      results suggest that fluoxetine accumulates in mussel tissue and has the
      potential to disrupt several aspects of reproduction in freshwater mussels, a
      faunal group recognized as one of the most imperiled in the world. Despite the
      disparity between measured environmental concentrations of fluoxetine and effects
      concentrations in our short-term tests with these long-lived animals, additional
      tests are warranted to evaluate the effects of long-term exposure to
      environmentally relevant concentrations and critical lifestages (e.g.,
      juveniles).

PMID- 20821575
TI  - Uptake and elimination of perfluorinated phosphonic acids in the rat.
AB  - The mono- and di-substituted perfluorinated phosphonic acids (mono-PFPAs and di
      PFPAs) are high production volume fluorinated surfactants. Mono-PFPAs have been
      observed in Canadian surface waters and wastewater treatment plant (WWTP)
      effluent. The first observation of the di-PFPAs in the environment is reported
      here, with the observation of the C6/C6 and C6/C8 di-PFPAs in the National
      Institute for Standards and Technology (NIST) WWTP sludge standard reference
      material (SRM) 2781. To characterize the risk associated with human exposure to
      the mono-PFPAs and di-PFPAs, we determined uptake and elimination parameters in
      the rat. After oral gavage all of the mono-PFPA and di-PFPA congeners were
      observed in the blood of the dosed animals. Half-lives after intraperitoneal
      dosing ranged from 0.96 +/- 0.11 to 2.8 +/- 0.5 days for the mono-PFPAs and 1.8
      +/- 0.1 to 9.3 +/- 1.5 days for the di-PFPAs. These half-lives are of similar
      magnitude to those for perfluorooctane sulfonate (PFOS, 8 to 30 days in male
      rats) and perfluorooctanoate (PFOA, 6 days in male rats and 1 hour in female
      rats). Both PFOS and PFOA have human half-lives on the order of years, and so the
      mono-PFPAs and di-PFPAs may also have significant lifetimes in the human body.
      The analysis of paired whole blood and plasma samples demonstrated that the mono
      PFPAs may bind to blood cells underestimating their concentration in plasma and
      sera samples. The biological fate of the mono-PFPAs and di-PFPAs determined here
      suggest there is the potential for human exposure and that if exposure does
      occur, they may be long-lived in the body.

PMID- 20821576
TI  - Fate and effects of Composition B in multispecies marine exposures.
AB  - The vast majority of investigations into the bioavailability and toxicity of
      explosives to receptors in aquatic environments has focused on deriving toxicity
      metrics for discrete chemical exposures to single species using pure compounds at
      relatively high concentrations. This study assessed the environmental fate and
      potential for biological effects of a common military formulation, Composition B,
      under more realistic exposure scenarios (e.g., those that more closely simulate a
      breached artillery round or residual exposure following a low-order detonation).
      We used a novel approach incorporating multiple species and toxicity endpoints in
      sediment exposures over a 34-d exposure period. Composition B fragments exposed
      at the sediment surface rapidly released 2,4,6-trinitrotolune (TNT) and hexahydro
      1,3,5-trinitro-1,3,5-triazine (RDX) to the overlying water column. In comparison,
      burial of fragments resulted in dramatically reduced exposure, bioconcentration,
      and toxicity. The addition of a conservative flow rate to the aquaria also
      reduced water and tissue concentrations by factors of two to three. Although the
      exposure system likely represented a worst-case scenario relative to most
      conditions found in coastal and estuarine environments, overlying water
      concentrations generally did not approach known toxicity thresholds, while
      porewater concentrations were sufficiently elevated above toxicity thresholds
      immediately adjacent to the fragments, limiting hazardous exposure only to very
      localized scales. Bioconcentration correlated closely with observed toxicity and
      was either not detectable (buried), or low (exposed), as is expected based on the
      low hydrophobicities of TNT and RDX.

PMID- 20821577
TI  - Influence of stability on the acute toxicity of CdSe/ZnS nanocrystals to Daphnia
      magna.
AB  - The acute toxicity of polymer-coated CdSe/ZnS quantum dots (QDs) to Daphnia magna
      was investigated using 48-h exposure studies. The principal objective was to
      relate the toxicity of QDs to specific physical and chemical aspects of the QD.
      As such, two different CdSe core diameters, 2 nm QDs (green-emitting) and 5 nm
      QDs (red-emitting), and two different surface coatings, polyethylene oxide (PEO)
      and 11-mercaptoundecanoic acid (MUA) were studied. The QDs were characterized
      before and after the 48-h exposure using fluorescence, ultrafiltrations (3 kDa),
      and inductively coupled plasma-atomic emission spectrometry (ICP-AES) metal
      analysis. In addition, flow field flow fractionation-inductively coupled plasma
      mass spectrometry (Fl FFF-ICP-MS) was used as a more extensive characterization
      technique to determine particle size and composition as well as identify other
      potential constituents in the QD solutions. The more stable QDs (PEO) were found
      to be less acutely toxic than the QDs with accelerated dissolution (MUA),
      suggesting QD stability has significant impact on the nanoparticles' short-term
      toxicity. The emergence of dissolved Cd(2+) in solution indicates that the
      toxicity of the MUA QDs is likely due to Cd poisoning, and a mass-based dose
      response occurred as a consequence of this mode of action. Alternatively, the PEO
      QDs caused acute toxicity without observed particle dissolution (i.e., no
      detectable metals were solubilized), suggesting an alternative mode of toxic
      action for these nanoparticles. Results of the present study suggest that using
      particle number, instead of mass, as a dose metric for the PEO QDs, produces
      markedly different conclusions, in that smaller core size does not equate to
      greater toxicity.

PMID- 20821578
TI  - Quick assessment of cytotoxins effect on Daphnia magna using in vivo fluorescence
      microscopy.
AB  - A novel approach to contaminant toxicity screening is proposed. The use of
      fluorescent microscopy with fluorescent dyes allows for assessing intoxication of
      Daphnia magna tissues, at various stages of exposure, to contaminants present in
      water. As shown, D. magna may not only be used as a test species in toxicity
      tests based on its lethality, but due to its translucency and application of
      fluorescent probes, separate steps of its intoxication and dying can be
      visualized. Using a variety of fluorescent probes, the present study also
      contributes to a better understanding of the toxicity mechanisms.

PMID- 20821579
TI  - Simulating climate change-induced alterations in bioaccumulation of organic
      contaminants in an Arctic marine food web.
AB  - Climate change is expected to alter environmental distribution of contaminants
      and their bioaccumulation due to changes in transport, partitioning, carbon
      pathways, and bioaccumulation process rates. Magnitude and direction of these
      changes and resulting overall bioaccumulation in food webs is currently not
      known. The present study investigates and quantifies the effect of climate change
      in terms of increased temperature and primary production (i.e., concentrations of
      particulate organic carbon, C(POC)), on bioaccumulation of organic contaminants
      in biota at various trophic levels. The present study covers only parts of the
      contaminant behavior that is influenced by climate change, and it was assumed
      that there were no changes in food web structure and in total air and water
      concentrations of organic contaminants. Therefore, other climate change-induced
      effects on net bioaccumulation, such as altered contaminant transport and food
      web structure, should be addressed in future studies. To determine the effect of
      climate change, a bioaccumulation model was used on the pelagic marine food web
      of the Arctic, where climate change is expected to occur fastest and to the
      largest magnitude. The effect of climate change on model parameters and
      processes, and on net bioaccumulation, were quantified for three modeling
      substances (gamma-hexachlorocyclohexane [HCH], polychlorinated biphenyl [PCB]-52,
      and PCB-153) for two possible climate scenarios. In conclusion, increased
      temperature and C(POC) reduced the overall bioaccumulation of organic
      contaminants in the Arctic marine food web, with the largest change being for PCB
      52 and PCB-153. Reduced bioavailability, due to increased C(POC), was the most
      influential parameter for the less water soluble compounds. Increase in
      temperature resulted in an overall reduction in net bioaccumulation.

PMID- 20821580
TI  - Integrated assessment of oil pollution using biological monitoring and chemical
      fingerprinting.
AB  - A full assessment of the impact of oil and chemical spills at sea requires the
      identification of both the polluting chemicals and the biological effects they
      cause. Here, a combination of chemical fingerprinting of surface oils, tissue
      residue analysis, and biological effects measures was used to explore the
      relationship between spilled oil and biological impact following the grounding of
      the MSC Napoli container ship in Lyme Bay, England in January 2007. Initially,
      oil contamination remained restricted to a surface slick in the vicinity of the
      wreck, and there was no chemical evidence to link biological impairment of
      animals (the common limpet, Patella vulgata) on the shore adjacent to the oil
      spill. Secondary oil contamination associated with salvage activities in July
      2007 was also assessed. Chemical analyses of aliphatic hydrocarbons and terpanes
      in shell swabs taken from limpet shells provided an unequivocal match with the
      fuel oil carried by the ship. Corresponding chemical analysis of limpet tissues
      revealed increased concentrations of polycyclic aromatic hydrocarbons (PAHs)
      dominated by phenanthrene and C1 to C3 phenanthrenes with smaller contributions
      from heavier molecular weight PAHs. Concurrent ecotoxicological tests indicated
      impairment of cellular viability (p < 0.001), reduced immune function (p <
      0.001), and damage to DNA (Comet assay, p < 0.001) in these animals, whereas
      antioxidant defenses were elevated relative to un-oiled animals. These results
      illustrate the value of combining biological monitoring with chemical
      fingerprinting for the rapid identification of spilled oils and their sublethal
      impacts on biota in situ.

PMID- 20821581
TI  - Characterization of the androgen-sensitive MDA-kb2 cell line for assessing
      complex environmental mixtures.
AB  - Synthetic and natural steroidal androgens and estrogens and many other non
      steroidal endocrine-active compounds commonly occur as complex mixtures in
      aquatic environments. It is important to understand the potential interactive
      effects of these mixtures to properly assess their risk. Estrogen receptor
      agonists exhibit additivity in mixtures when tested in vivo and in vitro. Little
      is known, however, concerning possible mixture interactions of androgen receptor
      agonists. In these studies we used the MDA-kb2 cell line, a human breast cancer
      cell line with endogenous androgen receptors and a stably transfected luciferase
      reporter gene construct to quantify the androgenic activity of seven natural and
      synthetic androgens: 17beta-trenbolone, dihydrotestosterone, methyltestosterone,
      testosterone, trendione, 17alpha-trenbolone, and androstenedione. We tested
      combinations of these androgens and compared the observed activity to expected
      androgenic activity based on a concentration addition model. Our analyses support
      the hypothesis that androgen receptor agonists cause additive responses in a
      mixture. Binary mixtures of 17beta-trenbolone with 17beta-estradiol or
      triclocarban (an anti-microbial found in the environment) were also tested.
      17beta-Estradiol induced androgenic activity, but only at concentrations 600-fold
      greater than those found in the environment. Triclocarban enhanced the activity
      of 17beta-trenbolone. Additionally, three anti-androgens were each paired with
      three androgens of varying potencies. The relative potencies of the antagonists
      were a vinclozolin metabolite (M2) > procymidone > prochloraz regardless of the
      androgen used. The results of our studies demonstrate the potential utility of
      the androgen-responsive MDA-kb2 cell line for quantifying the activity of
      mixtures of endocrine-active chemicals in complex wastes such as municipal
      effluents and feedlot discharges.

PMID- 20821582
TI  - Occurrence and a screening-level risk assessment of human pharmaceuticals in the
      Pearl River system, South China.
AB  - Ten nonsteroidal antiinflammatory drugs (NSAIDs), two blood lipid regulators
      (BLRs), and two antiepileptic drugs (AEDs) were analyzed in the Pearl River
      system in China (i.e., Liuxi, Zhujiang, and Shijing Rivers) and four sewage
      effluents during the dry and wet seasons, and the environmental risks they posed
      were assessed. Eight pharmaceuticals were detected in the rivers and effluents,
      including five NSAIDs (salicylic acid, ibuprofen, diclofenac, mefenamic acid, and
      naproxen), two BLRs (clofibric acid and gemfibrozil), and one AED
      (carbamazepine). The median concentrations for the eight pharmaceuticals ranged
      from 11.2 to 102 ng/L. Seasonal variations were not obvious for most
      pharmaceuticals in the three rivers, except for salicylic acid and clofibric acid
      in the Zhujiang River, and diclofenac in the Zhujiang and Shijing Rivers.
      However, spatially considerable variations in the concentrations were observed
      for the eight pharmaceuticals in all three rivers. For most of the
      pharmaceuticals, the effluents from the four wastewater treatment plants and
      Shijing River water were found to be the major discharge sources for the Zhujiang
      River, but with additional discharge sources from some small urban streams in the
      wet season. Diclofenac in the Shijing River was the only pharmaceutical that had
      a risk quotient (RQ) >1, indicating a high risk to aquatic organisms in the
      river. Although higher RQs were calculated for the mixture of the pharmaceuticals
      in each river, the risk rating remained the same for the three rivers with the RQ
      being >1 only in Shijing River.

PMID- 20821583
TI  - Food web bioaccumulation model for polychlorinated biphenyls in San Francisco
      Bay, California, USA.
AB  - We document the development and application of a food web bioaccumulation model
      for polychlorinated biphenyls (PCBs) in San Francisco Bay, California, USA. The
      model calculates spatial distributions of PCB concentrations in a range of
      invertebrate, fish, avian, and mammalian organisms, including harbor seals,
      double-crested cormorants, and Forster's terns. The performance of the model is
      evaluated against independent empirical PCB concentrations and shows a mean
      deviation between observed and model-calculated concentrations of 36% for female
      harbor seals and 5% for benthic invertebrates and jack smelt. The model was
      applied to produce bay-wide PCB concentration distributions in fish and wildlife
      species, which were compared with threshold effect concentrations to determine
      ecological risks and human health risks of fish consumption. Because of their
      high trophic position in the food web, harbor seals exhibited the highest
      concentrations of summation operatorPCBs, which exceeded threshold concentrations
      for potential adverse effects. The model was also applied to derive bay-wide
      target sediment concentrations for remediation as part of an ongoing total
      maximum daily loading characterization. The model calculated bay-wide geometric
      mean concentrations of summation operatorPCB in sediments of 1.6 to 73 microg/kg
      dry weight to meet several ecological and human health risk objectives. The bay
      wide geometric summation operatorPCB concentration in the sediments at the time
      of the study was 11.6 microg/kg dry weight. The model was developed for assessing
      the behavior and risks of bioaccumulative substances on an ecosystem level.

PMID- 20821584
TI  - Time is of the essence.
AB  - An organism is a dynamic system, and its life history results from underlying
      processes in time. The effects of biological and chemical stressors on this
      system therefore also change temporally. In the present short communication, we
      emphasize the importance of including time as a factor in stress ecology and
      ecotoxicology and argue that current standard test protocols may benefit
      considerably from this, improving data interpretation and thus also risk
      assessment and risk management.

PMID- 20821586
TI  - Multiple facets of environmental impacts from Hurricane Katrina.

PMID- 20821587
TI  - Sediment quality in near coastal waters of the Gulf of Mexico: influence of
      Hurricane Katrina.
AB  - The results of the present study represent a synoptic analysis of sediment
      quality in coastal waters of Lake Pontchartrain and Mississippi Sound two months
      after the landfall of Hurricane Katrina. Posthurricane conditions were compared
      to prehurricane (2000-2004) conditions, for sediment quality data. There were no
      exceedances of effects range median (ERM) sediment quality guideline values for
      chemical contaminants in any of the sediment samples collected from the Lake
      Pontchartrain or the Mississippi Sound study areas following the hurricane. Lower
      threshold effects range low (ERL) values were exceeded for As, Cd, and Ni at
      several stations in both survey areas, similar to levels of contamination
      observed prior to the hurricane. The comparison of sediment quality indicators
      before and after the hurricane suggests considerable stability of these systems
      with respect to short-term ecological impacts. Although other studies have shown
      storm-related changes could be detected (e.g., effects on benthic communities
      associated with shifts in salinity), there were no indications of widespread
      sediment contamination.

PMID- 20821588
TI  - Use of bioassays and sediment polycyclic aromatic hydrocarbon concentrations to
      assess toxicity at coastal sites impacted by Hurricane Katrina.
AB  - The goal of the present study was twofold: to rapidly assess the potential
      environmental toxicological response following the storm surge and flooding
      caused by Hurricane Katrina along the Gulf Coast of Mississippi, USA, in August
      2005, and to establish post-Katrina baseline toxicological profiles for three
      environmental matrices (water, suspended sediments, and sediments) within the
      intertidal zone. Sediment and water samples were collected monthly from September
      2005 to 2006 from 10 sites along the Gulf Coast from Gulfport, Mississippi, to
      Mobile Bay, Alabama. Water samples and suspended sediment matrices were
      extracted, assayed, and toxic equivalent values calculated for compounds with
      estrogenic potential, using the yeast estrogen screen, and CYP1A induction
      potential, using the H4IIE rat hepatoma ethoxyresorufin-O-deethylase assay.
      Polycyclic aromatic hydrocarbons (PAHs) were measured in surface sediments. It
      was hypothesized that the more heavily storm impacted sites, those closest to
      Katrina's path and time of landfall (e.g., Gulfport, September-October 2005),
      would elicit higher bioassay responses and PAH concentrations compared to those
      further east or approximately a year post-Katrina (e.g., Mobile Bay, August-
      September 2006). Benzo[a]pyrene equivalents decreased along spatial and temporal
      storm intensity gradients, but estrogenic compounds and sediment PAHs did not.
      Estrogen equivalents (approximately 1 ng/L) from water and suspended sediment
      samples occurred primarily in samples collected within a few months post-Katrina.
      Site-averaged surface sediment total PAHs varied significantly between sites and
      were higher than the U.S. National Oceanic and Atmospheric Administration's
      probable effects level at the Gulfport Marina and Back Biloxi Bay, Mississippi,
      sites. Results from the present study suggest that CYP1A inducing compounds
      elicited a short-term bioassay response in the water matrix shortly (within
      weeks) after Katrina's passing but were quickly reduced.

PMID- 20821589
TI  - Toxic trace element assessment for soils/sediments deposited during Hurricanes
      Katrina and Rita from southern Louisiana, USA: a sequential extraction analysis.
AB  - Analysis of soil/sediment samples collected in the southern Louisiana, USA,
      region three weeks after Hurricanes Katrina and Rita passed was performed using
      sequential extraction procedures to determine the origin, mode of occurrence,
      biological availability, mobilization, and transport of trace elements in the
      environment. Five fractions: exchangeable, bound to carbonates, bound to iron
      (Fe)-manganese (Mn) oxides, bound to organic matter, and residual, were
      subsequently extracted. The toxic trace elements Pb, As, V, Cr, Cu, and Cd were
      analyzed in each fraction, together with Fe in 51 soil/sediment samples. Results
      indicated that Pb and As were at relatively high concentrations in many of the
      soil/sediment samples. Because the forms in which Pb and As are present tend to
      be highly mobile under naturally occurring environmental conditions, these two
      compounds pose an increased health concern.Vanadium and Cr were mostly associated
      with the crystal line nonmobile residual fraction. A large portion of the Cu was
      associated with organic matter and residual fraction. Cadmium concentrations were
      low in all soil/sediment samples analyzed and most of this element tended to be
      associated with the mobile fractions. An average of 21% of the Fe was found in
      the Fe-Mn oxide fraction, indicating that a substantial part of the Fe was in an
      oxidized form. The significance of the overall finding of the present study
      indicated that the high concentrations and high availabilities of the potentially
      toxic trace elements As and Pb may impact the environment and human health in
      southern Louisiana and, in particular, the New Orleans area.

PMID- 20821590
TI  - Lead distributions and risks in New Orleans following Hurricanes Katrina and
      Rita.
AB  - During the last four years, significant effort has been devoted to understanding
      the effects that Hurricanes Katrina and Rita had on contaminant distribution and
      redistribution in New Orleans, Louisiana, USA, and the surrounding Gulf Coast
      area. Elevated concentrations were found for inorganic contaminants (including
      As, Fe, Pb, and V), several organic pollutants (polycyclic aromatic hydrocarbons,
      pesticides, and volatiles) and high concentration of bioaerosols, particularly
      Aeromonas and Vibrio. Data from different research groups confirm that some
      contaminant concentrations are elevated, that existing concentrations are similar
      to historical data, and that contaminants such as Pb and As may pose human health
      risks. Two data sets have been compiled in this article to serve as the
      foundation for preliminary risk assessments within greater New Orleans. Research
      from the present study suggests that children in highly contaminated areas of New
      Orleans may experience Pb exposure from soil ranging from 1.37 microg/d to 102
      microg/d. These data are critical in the evaluation of children's health.

PMID- 20821591
TI  - Air quality during demolition and recovery activities in post-Katrina New
      Orleans.
AB  - Air samples were collected during demolition and cleanup operations in the
      Lakeview district of New Orleans, Louisiana, USA, in late 2005 during the period
      immediately after Hurricane Katrina. Three different high-volume air samples were
      collected around waste collection areas that were created to temporarily hold the
      debris from the cleanup of residential properties in the area. Particulate
      concentrations were elevated and included crystalline fibers associated with
      asbestos. Metal concentrations on particulate matter resembled those measured in
      sediments deposited by floodwaters with the exception of Ba, which was elevated
      at all three locations. The highest organic contaminant concentration measured on
      particulates was the pesticide Ziram (Zinc, bis[diethylcarbamodithioato-S,S']-,
      [T-4]-) at 2,200 microg/g of particulate matter during sampling period 2. Ziram
      is used in latex paint, adhesives, caulking, and wallboard as a preservative.
      Fungal isolates developed from particulate air samples included species
      associated with disease including Aspergillus and Penicillium species. These data
      represent the most comprehensive assessment of demolition activities during the
      period immediately after Hurricane Katrina.

PMID- 20821592
TI  - Mechanistic link between uptake of sulfonamides and bacteriostatic effect: model
      development and application to experimental data from two soil microorganisms.
AB  - Sulfonamides (SA) are antibiotic compounds that are widely used as human and
      veterinary pharmaceuticals. They are not rapidly biodegradable and have been
      detected in various environmental compartments. Effects of sulfonamides on
      microbial endpoints in soil have been reported from laboratory incubation
      studies. Sulfonamides inhibit the growth of sensitive microorganisms by
      competitive binding to the dihydropteroate-synthase (DHPS) enzyme of folic acid
      production. A mathematical model was developed that relates the extracellular SA
      concentration to the inhibition of the relative bacterial growth rate. Two
      factors--the anionic accumulation factor (AAF) and the cellular affinity factor
      (CAF)--determine the effective concentration of an SA. The AAF describes the SA
      uptake into bacterial cells and varies with both the extra- and intracellular pH
      values and with the acidic pKa value of an SA. The CAF subsumes relevant cellular
      and enzyme properties, and is directly proportional to the DHPS affinity constant
      for an SA. Based on the model, a mechanistic dose-response relationship is
      developed and evaluated against previously published data, where differences in
      the responses of Pseudomonas aeruginosa and Panthoea agglomerans toward changing
      medium pH values were found, most likely as a result of their diverse pH
      regulation. The derived dose-response relationship explains the pH and pKa
      dependency of mean effective concentration values (EC50) of eight SA and two soil
      bacteria based on AAF and CAF values. The mathematical model can be used to
      extrapolate sulfonamide effects to other pH values and to calculate the CAF as a
      pH-independent measure for the SA effects on microbial growth.

PMID- 20821593
TI  - Measurements of acid volatile sulfide and simultaneously extracted metals are
      irreproducible among laboratories.
AB  - Partitioning with solid phases is a principal control on availability and
      associated toxicity of metals to aquatic biota. In anoxic sediments,
      environmentally active fractions of sulfide and associated metals are defined
      operationally as acid-volatile sulfide (AVS) and simultaneously extracted metals
      (SEM). Ratios of these chemical parameters are often used in establishing
      equilibrium partitioning sediment benchmarks for toxicity and, therefore, require
      analytical accuracy to be useful. To investigate the reproducibility and accuracy
      of AVS and SEM measurements, we distributed subsamples of four physicochemically
      disparate stream sediments to seven independent laboratories, including our own,
      for analysis of both AVS and SEM (Cd, Cu, Pb, Ni, and Zn). Synthesis of these
      results shows that AVS varied from 70 to 3,500x and SEM ranged from 17 to 60x
      among laboratories for each of the four sediments. Inadequate detection limits
      for AVS precluded calculation of SEM:AVS ratios for two of the deposits, whereas
      the ratio varied more than 50-fold among laboratories for the other two
      sediments. This work highlights the need for improved quality control and
      standardization of methods for determination of AVS and SEM in sediments, and
      suggests that predictions of metal toxicity in sediments can be laboratory
      specific, which raises concerns on the use of the AVS:SEM model for risk
      assessments and regulatory decisions.

PMID- 20821594
TI  - Predicting mercury concentrations and fluxes in the water column and sediment of
      lakes with a limited dataset.
AB  - The purpose of the present study was to evaluate the mercury (Hg) Environmental
      Ratios Multimedia Ecosystem Sources (HERMES) model on two Ontario, Canada lakes
      (Harp and Dickie) and to include modifications to enable the model to estimate
      the major model input variables that tend to be missing for lakes with limited
      datasets. No significant differences were found for either sediment solid or bulk
      water total mercury (THg) when the HERMES model was applied to the two Ontario
      lakes, regardless of whether all available data were altered during application
      or only the 10 variables that tend to cause the most variation in model output
      (i.e., concentration of THg in atmosphere, water inflow THg concentration, water
      inflow rate, water volume, surface area, mean depth, suspended particulate matter
      concentration, settling rate of solids in water column, water temperature, and
      precipitation rate). Since measured sediment and water THg values do not exist
      for most lakes removed from industrial activities, empirical relationships were
      incorporated into the HERMES model framework to provide a method to double-check
      model output for lakes where this information is unavailable.

PMID- 20821595
TI  - Modeling the environmental fate of perfluorooctanoic acid and perfluorooctanoate:
      An investigation of the role of individual species partitioning.
AB  - A multimedia multi-species environmental fate model was developed for the
      conjugate pair perfluorooctanoic acid (PFOA):perfluorooctanoate (PFO). The model
      allows assessment of the relative contribution of each individual species, in
      equilibrium with each other, to the overall environmental movement of the pair.
      The Lake Ontario (Canada/USA) watershed system was selected for this
      investigation and is simulated in a single-region, seven-compartment model,
      including a water surface microlayer, and aqueous aerosol generation and
      redeposition. Results indicate that in the equilibrated presence of both PFOA and
      PFO, the environmental fate of the pair can be accomplished by consideration of
      the physical properties of the neutral acid, which govern the intermedia
      distribution of the pair, coupled with processes of media advection, such as air
      or water flow. The role of the anion, while the most populous species in the
      aqueous phase, appears merely to be as a source of the neutral acid for
      subsequent partitioning. Thus, when only the bulk aqueous phase anion
      concentrations are of interest a multimedia fate model is not required because
      these concentrations are largely predictable from the magnitude of emissions to
      and the advection of the phase. With neutral species partitioning, all local
      field measurement concentrations of the conjugate pair, PFO(A), are explained by
      the model to within approximately an order of magnitude, with the exception of
      lake sediment solids. Model results indicate that bulk aqueous phase PFO acts as
      a net source for PFOA to the atmosphere, where it may be subject to long-range
      transport (LRT). Initial calculations suggest an atmospheric LRT potential for
      PFO(A) of thousands of kilometers, rendering it comparable to hexachlorobenzene.

PMID- 20821596
TI  - Impact of changes in analytical techniques for the measurement of polychlorinated
      biphenyls and organochlorine pesticides on temporal trends in herring gull eggs.
AB  - Changes in analytical approaches during the tenure of monitoring programs for
      organochlorine (OC) pesticides and polychlorinated biphenyls (PCBs) may affect
      estimates of temporal trends. We used an in-house reference material to create
      multiplication factors to adjust the estimates of OC pesticides and PCBs (Aroclor
      equivalents) in Great Lake herring gull eggs analyzed using electron capture
      detection (1987-1997) to be more equivalent to estimates using mass spectrometric
      detection (1998-2005) as well as accompanying differences in analytical
      procedures. We examined temporal trends in contaminant concentrations in herring
      gull eggs using change point regressions, to determine whether significant
      changes in long-term trends were associated with analytical methodology. The
      highest frequency of change point occurrences shifted from 1997 (when analytical
      methodology was altered) to 2003 after data adjustment. The explanatory power
      (r2) of the regressions was lower after adjustment, although only marginally so
      (mean r2 difference=0.04). The initial rates of decline before change points in
      contaminant concentrations were generally slower after the data adjustment, but
      after any change points the declines were not significantly different. The
      regression models did not change for 83.3% of the cases. The effects on the
      interpretation of long-term temporal trends in herring gull eggs, although not
      negligible, were minor relative to the magnitude of the temporal changes.

PMID- 20821597
TI  - Occurrence of pharmaceuticals and hormones in sewage sludge.
AB  - The present study evaluates the presence of nine hormones and their conjugates
      and 20 pharmaceuticals such as anti-inflammatories, lipid regulators, and
      antibiotics among others in sewage sludge from two sewage treatment plants (STPs)
      in the Tarragona area (Spain) for the period March 2007 until March 2008. Target
      analytes have been determined using different methods involving pressurized
      liquid extraction and liquid chromatography (electrospray ionization) tandem mass
      spectrometry (MS-MS). Most of the pharmaceuticals and hormones were found at low
      micrograms per kilogram dry weight levels in the sewage sludge samples analyzed.
      Some compounds were present in all samples, such as acetaminophen, caffeine,
      carbamazepine, and ibuprofen, among others. Other compounds, such as estriol,
      were found only in the STP of Reus. The compounds that showed the highest
      concentration in both STPs were roxithromycin and tylosin (1,446 and 1,958
      microg/kg dry wt, respectively). The presence of these compounds in sewage sludge
      demonstrated that they are partially or totally removed from the influent
      wastewater by sorption into the sewage sludge.

PMID- 20821598
TI  - Effects of in ovo exposure of white leghorn chicken, common pheasant, and
      Japanese quail to 2,3,7,8-tetrachlorodibenzo-p-dioxin and two chlorinated
      dibenzofurans on CYP1A induction.
AB  - In birds, activation of the aryl hydrocarbon receptor (AhR) by some
      polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans
      (PCDFs) results in induction of cytochrome P4501A (CYP1A) expression. This
      response has been useful for predicting relative sensitivity of birds to dioxin
      like compounds. To further investigate species-sensitivity to dioxins and dioxin
      like compounds induction of cytochrome P450 1A4 and 1A5 (CYP1A4 and CYP1A5) mRNA
      and ethoxyresorufin O-deethylase (EROD) activity were quantified in liver of
      posthatch white leghorn chicken, common pheasant, and Japanese quail exposed to
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran
      (PeCDF), or 2,3,7,8-tetrachlorodibenzofuran (TCDF) via air cell injection. The
      rank-order of sensitivity of TCDD- and TCDF-exposed birds, based on CYP1A, was
      chicken>pheasant>quail. Based on CYP1A5 mRNA expression and EROD induction, the
      order of sensitivity of PeCDF-exposed birds was identical to that for TCDD and
      TCDF. However, based on CYP1A4 mRNA expression the rank-order was
      pheasant>chicken>quail. When comparing the potency of the three compounds in each
      species, based on CYP1A4 mRNA expression, TCDD was the most potent compound in
      chicken. However, PeCDF was equally potent to TCDD in quail and was more potent
      than TCDD in pheasant. These results suggest that quantitative real-time
      polymerase chain reaction (Q-PCR) analysis of CYP1A expression, particularly
      CYP1A4 mRNA expression, may be a more sensitive biomarker of exposure than
      analysis of EROD induction, especially in less responsive avian species. Based on
      these findings future risk assessments should consider the sensitivity of the
      species inhabiting a site and the congeners of concern that are present.

PMID- 20821599
TI  - Evaluating the biotic ligand model for toxicity and the alleviation of toxicity
      in terms of cell membrane surface potential.
AB  - The electrostatic nature of plant cell membrane (CM) plays significant roles in
      ionic interactions at the CM surface and hence in the biotic effects of metal
      ions. Increases in major cations (commonly Ca2+, Mg2+, H+, Na+, K+, etc.) in bulk
      phase medium reduce the negativity of CM surface electrical potential (psi0), but
      these slightly increase the driving force of a metal ion crossing CMs (surface-to
      surface transmembrane potential difference, Em,surf). Toxicologists commonly
      attributes the interactions between heavy metals and common cations (e.g., H+,
      Ca2+, and Mg2+) to competitions for binding sites at a hypothetical CM surface
      ligand. The psi0 effects are likely to be more important to metal toxicity and
      the alleviation of toxicity than site-specific competition. Models that do not
      consider psi0, such as the biotic ligand model (BLM) and the free ion activity
      model (FIAM), as usually employed are likely to lead to false conclusions about
      competition for binding at CM surface ligands. In the present study a model
      incorporating psi0 effects and site-specific competition effects was developed to
      evaluate metal (Cu2+, Co2+, and Ni2+) toxicities threshold (EA50, causing 50%
      inhibition) for higher plants. In addition, the mechanisms for the effects of
      common cations on toxicity of metals were also explored in terms of CM surface
      electrical potential.

PMID- 20821600
TI  - Dioxin transfer from sediment to the infaunal surface deposit-feeding polychaete
      Perinereis nuntia in a laboratory-rearing experiment.
AB  - In the presented study a laboratory experiment was conducted to investigate the
      transfer of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated
      dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (PCBs) from
      environmentally contaminated marine sediment to an infaunal surface deposit
      feeding polychaete, Perinereis nuntia. Polychaetes were exposed to contaminated
      sediment for 42 d, and elimination of these compounds was studied for an
      additional 28 d. The sediment uptake rate coefficients (ks), elimination rate
      constants (k2), and the biota-sediment accumulation factors (BSAFs) were
      determined for PCDDs, PCDFs (PCDD/Fs), and dioxin-like PCBs. Each of these
      compounds was transferred from sediment to polychaete except for hepta- and
      octachlorinated PCDD/Fs. The BSAFs for dioxin-like PCBs (0.13-2.2) were
      significantly higher than those for PCDD/Fs (0.00022-0.36). The BSAF, ks, and k2
      values obtained in the present study indicate that the bioaccumulation
      characteristics of PCDD/Fs in polychaete are similar to those in fish, and depend
      on their physical and chemical properties such as hydrophobicity and size of
      molecules. The ks values for PCDD/Fs and dioxin-like PCBs declined with an
      increase in their log KOW values, indicating a decrease in bioavailability. The
      negative exponential relationships of k2 versus KOW were observed for these
      compounds. The slope for the log-normalized regression of k2 versus KOW for the
      PCDD/Fs was smaller than that for the dioxin-like PCBs and that of ks versus KOW
      for the PCDD/Fs. Therefore, the negative exponential relationship of BSAF versus
      KOW was observed for PCDD/Fs, but not for dioxin-like PCBs.

PMID- 20821601
TI  - Particle-specific sorption/desorption properties determine test compound fate and
      bioavailability in toxicity tests with Chironomus riparius--high-resolution
      studies with lindane.
AB  - We studied the sorption (batch equilibrium experiments) and desorption
      (consecutively harsher supercritical fluid extractions) of lindane to different
      types of sediment and food particles, as well as larval uptake in standardized
      peat-based artificial sediment toxicity tests with the midge Chironomus riparius.
      Lindane sorption to organic particles was fast and efficient, reaching 98+/-0.1
      and 97+/-0.1% of added compound in 48 h for peat and Tetraphyll(R), respectively,
      and 77+/-0.2% in whole sediment. Sorption to inorganic particles, that is, sand
      and kaolin clay, was much lower, 9.6+/-1.3% and 8.3+/-0.8%, respectively.
      Supercritical fluid extractions showed that most of the lindane sorbed to organic
      particles and sediment was loosely bound, as only 9 to 14% remained associated
      with particles after weak and intermediate extractions strengths. Larval uptake
      of dissolved lindane was 4.9+/-0.71 and 10.8+/-1.2 microg/g wet weight in 22 and
      68 microg/L treatments, respectively, and four to five times higher than that of
      particle-associated lindane, ranging 1.0+/-0.15 to 2.7+/-0.21 microg/g in the
      above treatments. Surprisingly, larval uptake of lindane was similar from
      refractory peat and the more labile Tetraphyll particles. Despite an efficient
      larval uptake of dissolved lindane, sorption/desorption of lindane to/from
      Tetraphyll particles will facilitate digestive uptake in toxicity tests,
      particularly in spiked-water scenarios where food particles may act as vectors.
      Our results show that the exposure scenario is an important determinant for the
      behavior and bioavailability of test compounds in standardized toxicity tests.

PMID- 20821602
TI  - Specific in vitro toxicity of crude and refined petroleum products: II. Estrogen
      (alpha and beta) and androgen receptor-mediated responses in yeast assays.
AB  - The present study is the second in a series aiming at a systematic inventory of
      specific toxic effects of oils. By employing a recombinant yeast stably
      transfected with human estrogen receptor-alpha (ERalpha) or -beta (ERbeta) or
      androgen receptor (AR) and expressing yeast enhanced green fluorescent protein,
      the (anti-)estrogenicity and (anti-)androgenicity of 11 crude oils and refined
      products were studied. None of the oils tested had significant estrogenic effects
      in the ERalpha assay or androgenic effects in the AR assay. However, all oils
      were capable of inducing estrogenic responses in the ERbeta assay, with several
      responses being above even the maximal response of the standard 17beta-estradiol
      (E2). Based on the lowest effect concentrations, the potencies of oils in all the
      assays were between four and seven orders of magnitude lower than those of the
      standards E2 or testosterone (T). The potencies of the actual individual
      petrochemical agonists may, however, be relatively high, considering the complex
      composition of oils. Additive effects, antagonistic effects, and a synergistic
      effect were measured in the assays upon coexposure to a fixed concentration of
      standard (E2 or T) and increasing concentrations of oils. To investigate whether
      the observed effects were receptor-mediated, coexposures to the synthetic
      inhibitors ICI 182,780 (ERbeta assay) or flutamide (AR assay), a fixed
      concentration of standard, and various concentrations of oils were performed. The
      results suggested that the androgenic effects were receptor mediated, whereas the
      estrogenic effects may be only partially mediated via the receptor. The present
      study indicates that oils contain compounds with possible endocrine-disrupting
      potential, some of them acting via the hormone receptors.

PMID- 20821603
TI  - Dose-response relationship, kinetics of formation, and persistence of S-[2-(N7
      guanyl)-ethyl]glutathione-DNA adduct in livers of channel catfish (Ictalurus
      punctatus) exposed in vivo to ethylene dichloride.
AB  - Formation of DNA adducts by reactive chemicals or their metabolites are often a
      precursor of mutagenesis and other adverse effects. Studies in juvenile channel
      catfish (Ictalurus punctatus) were conducted to determine the dose-response,
      kinetics of formation, and persistence of S-[2-(N7-guanyl)ethyl]glutathione
      hepatic-DNA adducts following a 4-h in vivo aqueous exposure to ethylene
      dichloride (EDC) at several dose levels. S-[2-(N7-guanyl)ethyl] glutathione
      adducts were detectable in liver tissue after 2 h of exposure and were still
      detectable three weeks after a single pulse exposure (detection
      limit=approximately 10 fmol, approximately 1 DNA adduct in 10(7) bases).
      Pretreatment of catfish with the glutathione-depleting agent diethylmaleate
      significantly reduced the level of tissue glutathione levels and, as a result,
      DNA adducts were not detected in pretreated fish. Catfish may serve as a useful
      sentinel species for detecting DNA-reactive chemicals in aquatic systems.

PMID- 20821604
TI  - An evaluation of the ability of chemical measurements to predict polycyclic
      aromatic hydrocarbon-contaminated sediment toxicity to Hyalella azteca.
AB  - The present study examined the ability of three chemical estimation methods to
      predict toxicity and nontoxicity of polycyclic aromatic hydrocarbon (PAH) 
      contaminated sediment to the freshwater benthic amphipod Hyalella azteca for 192
      sediment samples from 12 field sites. The first method used bulk sediment
      concentrations of 34 PAH compounds (PAH34), and fraction of total organic carbon,
      coupled with equilibrium partitioning theory to predict pore-water concentrations
      (KOC method). The second method used bulk sediment PAH34 concentrations and the
      fraction of anthropogenic (black carbon) and natural organic carbon coupled with
      literature-based black carbon-water and organic carbon-water partition
      coefficients to estimate pore-water concentrations (KOCKBC method). The final
      method directly measured pore-water concentrations (pore-water method). The U.S.
      Environmental Protection Agency's hydrocarbon narcosis model was used to predict
      sediment toxicity for all three methods using the modeled or measured pore-water
      concentration as input. The KOC method was unable to predict nontoxicity (83% of
      nontoxic samples were predicted to be toxic). The KOCKBC method was not able to
      predict toxicity (57% of toxic samples were predicted to be nontoxic) and,
      therefore, was not protective of the environment. The pore-water method was able
      to predict toxicity (correctly predicted 100% of the toxic samples were toxic)
      and nontoxicity (correctly predicted 71% of the nontoxic samples were nontoxic).
      This analysis clearly shows that direct pore-water measurement is the most
      accurate chemical method currently available to estimate PAH-contaminated
      sediment toxicity to H. azteca.

PMID- 20821605
TI  - Dioxin-like and perfluorinated compounds in pigs in an Indian open waste dumping
      site: toxicokinetics and effects on hepatic cytochrome P450 and blood plasma
      hormones.
AB  - Dioxins and related compounds (DRCs) and perfluorinated compounds were measured
      in the livers of pigs (Sus scrofa) collected from an open waste dumping site in
      South India. Hepatic concentrations of DRCs and perfluorooctanesulfonate (PFOS;
      up to 200 ng/g wet wt) were significantly higher in male and female pigs,
      respectively, collected from the dumping site than in those from a reference
      site. Results suggest that dumping sites are a source of DRCs and PFOS. Hepatic
      concentrations of DRCs in piglets were higher than in mothers, especially for the
      congeners with molecular weights in the range of 360 to 400, implying congener
      specific maternal transfer of DRCs in swine. Concentrations of polychlorinated
      dibenzo-p-dioxins and dibenzofurans and some non-ortho dioxin-like
      polychlorinated biphenyls (PCBs) in the liver of pigs were higher than those in
      the adipose fat and muscle of the same specimens. In addition, the liver-to
      adipose concentration ratios for each congener had a significant positive
      correlation with the levels of hepatic cytochrome P450 (CYP)1A-like protein,
      suggesting congener-specific and CYP1A-dependent hepatic sequestration of DRCs in
      the swine. Total hepatic 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents
      (TEQs; 8.9-350 pg/g fat wt) had a significant positive correlation with CYP1A
      like protein expression (r=0.56, p=0.012), suggesting the induction of CYP1A by
      DRCs. However, the total TEQs had a significant negative correlation with CYP4A
      like protein (r=-0.49, p=0.029), suggesting repression of peroxisome proliferator
      activated receptor-alpha (PPARalpha)-mediated signaling pathway by DRCs.
      Decreases in plasma total thyroxine (T4), free T4, and immunoglobulin (Ig) G were
      also found in pigs from the dumping site compared with those from the reference
      site. This study provides insight into the toxicological impacts of DRCs and
      perfluorinated compounds in wild animals from open waste dumping sites.

PMID- 20821606
TI  - Dual enantioselective effect of the insecticide bifenthrin on locomotor behavior
      and development in embryonic-larval zebrafish.
AB  - Bifenthrin (BF) is a synthetic pyrethroid that targets the nervous system of
      insects and may have adverse effects on the behavior and development of nontarget
      organisms. However, no reports have been issued on the effects of different
      enantiomers on locomotor behavior for synthetic pyrethroids (SPs) in zebrafish,
      and whether locomotor activity is associated with the developmental toxicities
      remains unclear. In this study, enantioselectivity of BF (1S and 1R) on the acute
      locomotor activity and developmental toxicities of embryonic-larval zebrafish
      were first evaluated. The results indicated that 1R-BF was more toxic, causing
      morphological impairments, with a 96-h median effective concentration (EC50) of
      226 microg/L for pericardial edema and 145 microg/L for curved body axis.
      Administration of 20 microg/L of one enantiomer of BF had differential effects on
      the locomotor activity of zebrafish larvae at 4 d postfertilization (dpf) under
      alternating light and dark conditions. Larvae treated with 1R-BF were not
      sensitive to the alteration of light to dark, and the locomotor activities were
      reduced to a level similar to that observed in light, which otherwise increased
      rapidly and markedly. However, 1S-BF did not alter the general pattern of
      zebrafish response to the light or dark compared with the control. The results
      demonstrated that the differential effects on development might have contributed
      to the enantioselectivity in the locomotor activity. The consistency of
      enantioselectivity with insecticidal activity may also indicate a common mode of
      action. Furthermore, 1R-BF accelerated the spontaneous movement and hatching
      process, whereas 1S-BF seemed to be inhibitory. The results suggest the need to
      link behavioral changes to developmental toxicities in order to achieve more
      comprehensive health risk assessments of chiral pesticides.

PMID- 20821607
TI  - Uptake kinetics and subcellular compartmentalization of cadmium in acclimated and
      unacclimated earthworms (Eisenia andrei).
AB  - Acclimation to cadmium (Cd) levels exceeding background concentrations may
      influence the ability of earthworms to accumulate Cd with minimum adverse
      effects. In the present study, earthworms (Eisenia andrei) were acclimated by
      exposure to 20 mg/kg Cd (dry wt) in Webster soil for 28 d. A 224-d
      bioaccumulation test was subsequently conducted with both acclimated and
      unacclimated worms exposed in Webster soils spiked with 20 mg/kg and 100 mg/kg Cd
      (dry wt). Uptake kinetics and subcellular compartmentalization of Cd were
      examined. Results suggest that acclimated earthworms accumulated more Cd and
      required a longer time to reach steady state than unacclimated worms. Most of the
      Cd was present in the metallothionein (MT) fraction. Cadmium in the MT fraction
      increased approximately linearly with time and required a relatively longer time
      to reach steady state than Cd in cell debris and granule fractions, which quickly
      reached steady state. Cadmium in the cell debris fraction is considered
      potentially toxic, but low steady state concentrations observed in the present
      study would not suggest the potential for adverse effects. Future use of
      earthworms in ecological risk assessment should take into consideration pre
      exposure histories of the test organisms. A prolonged test period may be required
      for a comprehensive understanding of Cd uptake kinetics and compartmentalization.

PMID- 20821608
TI  - Assessing the fate and effects of nano aluminum oxide in the terrestrial
      earthworm, Eisenia fetida.
AB  - Nano-sized aluminum is currently being used by the military and commercial
      industries in many applications including coatings, thermites, and propellants.
      Due to the potential for wide dispersal in soil systems, we chose to investigate
      the fate and effects of nano-sized aluminum oxide (Al2O3), the oxidized form of
      nano aluminum, in a terrestrial organism. The toxicity and bioaccumulation
      potential of micron-sized (50-200 microm, nominal) and nano-sized (11 nm,
      nominal) Al2O3 was comparatively assessed through acute and subchronic bioassays
      using the terrestrial earthworm, Eisenia fetida. Subchronic (28-d) studies were
      performed exposing E. fetida to nano- and micron-sized Al2O3-spiked soils to
      assess the effects of long-term exposure. No mortality occurred in subchronic
      exposures, although reproduction decreased at >or=3,000 mg/kg nano-sized Al2O3
      treatments, with higher aluminum body burdens observed at 100 and 300 mg/kg; no
      reproductive effects were observed in the micron-sized Al2O3 treatments. In
      addition to toxicity and bioaccumulation bioassays, an acute (48-h) behavioral
      bioassay was conducted utilizing a soil avoidance wheel in which E. fetida were
      given a choice of habitat between control, nano-, or micron-sized Al2O3 amended
      soils. In the soil avoidance bioassays, E. fetida exhibited avoidance behavior
      toward the highest concentrations of micron- and nano-sized Al2O3 (>5,000 mg/kg)
      relative to control soils. Results of the present study indicate that nano-sized
      Al2O3 may impact reproduction and behavior of E. fetida, although at high levels
      unlikely to be found in the environment.

PMID- 20821609
TI  - Productivity, embryo and eggshell characteristics, and contaminants in bald
      eagles from the Great Lakes, USA, 1986 to 2000.
AB  - Chlorinated hydrocarbon concentrations in eggs of fish-eating birds from
      contaminated environments such as the Great Lakes of North America tend to be
      highly intercorrelated, making it difficult to elucidate mechanisms causing
      reproductive impairment, and to ascribe cause to specific chemicals. An
      information- theoretic approach was used on data from 197 salvaged bald eagle
      (Haliaeetus leucocephalus) eggs (159 clutches) that failed to hatch in Michigan
      and Ohio, USA (1986-2000). Contaminant levels declined over time while eggshell
      thickness increased, and by 2000 was at pre-1946 levels. The number of occupied
      territories and productivity increased during 1981 to 2004. For both the entire
      dataset and a subset of nests along the Great Lakes shoreline, polychlorinated
      biphenyls (SigmaPCBs, fresh wet wt) were generally included in the most
      parsimonious models (lowest-Akaike's information criterion [AICs]) describing
      productivity, with significant declines in productivity observed above 26
      microg/g SigmaPCBs (fresh wet wt). Of 73 eggs with a visible embryo, eight (11%)
      were abnormal, including three with skewed bills, but they were not associated
      with known teratogens, including SigmaPCBs. Eggs with visible embryos had greater
      concentrations of all measured contaminants than eggs without visible embryos;
      the most parsimonious models describing the presence of visible embryos
      incorporated dieldrin equivalents and dichlorodiphenyldichloroethylene (DDE).
      There were significant negative correlations between eggshell thickness and all
      contaminants, with SigmaPCBs included in the most parsimonious models. There
      were, however, no relationships between productivity and eggshell thickness or
      Ratcliffe's index. The SigmaPCBs and DDE were negatively associated with nest
      success of bald eagles in the Great Lakes watersheds, but the mechanism does not
      appear to be via shell quality effects, at least at current contaminant levels,
      while it is not clear what other mechanisms were involved.

PMID- 20821610
TI  - Hatching success and pesticide exposures in amphibians living in agricultural
      habitats of the South Okanagan Valley, British Columbia, Canada (2004-2006).
AB  - In 2004 to 2006, in the Okanagan Valley, British Columbia, Canada, we measured
      pesticides, water chemistry, and hatching success of Great Basin spadefoot (Spea
      intermontana), Pacific treefrog (Pseudacris regilla), Western toad (Bufo boreas),
      and Columbia spotted frog (Rana luteiventris). Predator-proof cages containing
      Gosner Stage 4 eggs were placed in ponds in nonagricultural reference sites in
      conventionally sprayed and organic orchards. Seventeen pesticides were detected
      in ponds in sprayed orchards but occurred at low concentrations (ng/L) except for
      diazinon (1,410 ng/L). Chloride, sulfate, conductivity, nitrate, and phosphorus
      showed significant differences among sites. Spadefoot mean hatching success
      ranged from 0 to 92% among sprayed orchards, whereas the range was 48 to 98.6%
      among organic orchards and 51 to 95.5% among reference sites. Mean hatching
      success for Pacific treefrog was 22.1 to 76.1% among sprayed orchards, whereas
      the range was 83.4 to 97.1% among reference sites. Although sample sizes were
      small and replication was low, we found that trends in hatching success of eggs
      of Western toad and Columbia spotted frogs were consistent with the other
      species. Variables that correlated negatively with amphibian hatching success
      included 12 pesticides and seven water chemistry parameters. However, stepwise
      regression found that, in 2005, atrazine accounted for 79% of the variation in
      spadefoot hatching success and, in 2006, atrazine, total nitrate, and
      chlorpyrifos accounted for 80%. For Pacific treefrog there were no significant
      correlations with pesticide concentrations; rather, hatching success correlated
      with water chemistry parameters. The present study also emphasizes the
      variability in species sensitivity and importance of incorporating water
      chemistry into the interpretation of water quality for amphibians.

PMID- 20821611
TI  - Effects of environmentally relevant concentrations of endosulfan, azinphosmethyl,
      and diazinon on Great Basin spadefoot (Spea intermontana) and Pacific treefrog
      (Pseudacris regilla).
AB  - We conducted dose-response exposures to compare the lethality of endosulfan,
      diazinon, and azinphosmethyl in the early-life stages of the Great Basin
      spadefoot (Spea intermontana) and the Pacific treefrog (Pseudacris regilla). Our
      experiment occurred in two 8-d phases: one, with developing embryos, and two,
      with Gosner Stage 27 tadpoles. Pesticide concentrations were representative of
      field-measured concentrations (60 ng/L of endosulfan, 50 ng/L of azinphosmethyl,
      and 350 ng/L of diazinon), in the same geographic areas where these species occur
      in British Columbia. Although the concentrations met the requirements for federal
      water quality guidelines, we observed mortalities, deformities, and other
      sublethal effects. Phase 1 consisted of exposing Gosner Stage 10 embryos in the
      pesticide solutions for a total of 8 d. Significant mortality of S. intermontana
      began posthatch in the highest lethal concentrations of the commercial
      formulations of endosulfan (Thiodan; LC20(8d)=2,672.7 ng/L) and diazinon
      (LC20(8d)>175,000 ng/L). Phase 2 compared behavior, morphology, and survival of
      captive-reared tadpoles exposed to the same 8-d experimental regime as the embryo
      experiment. Endosulfan induced significant effects on behavior and morphology of
      P. regilla and significantly reduced survivorship of S. intermontana
      (LC20(8d)=77.1 ng/L). Abnormal behavior and excitability was observed in both
      species, with P. regilla tadpoles being more sensitive. At 60,000 ng/L
      endosulfan, P. regilla also lost pigmentation and exhibited abnormal tail
      morphology.

PMID- 20821612
TI  - Mammalian glucocorticoid metabolites act as androgenic endocrine disruptors in
      the medaka (Oryzias latipes).
AB  - Glucocorticoid metabolites enter the aquatic environment via mammalian
      excrements. Molecular structures of their C19O3 metabolites strongly resemble the
      major fish androgen 11-ketotestosterone. Therefore, we tested the hypothesis that
      the cortisol metabolite 5alpha-androstan-3,11,17-trione acts similarly to 11
      ketotestosterone by employing a fish screening assay for endocrine-active
      substances. After 21 d, both 11-oxygenated compounds had masculinized sex
      characteristics of the anal fin in female medaka in a dose-dependent manner.

PMID- 20821613
TI  - Relating the ability of mallards to ingest high levels of sediment to potential
      contaminant exposure in waterfowl.
AB  - When waterfowl feed from the bottom of bodies of water, they sometimes ingest
      sediments along with their food, and this sediment can be a major source of
      contaminants. Learning how much sediment waterfowl can consume in their diet and
      still maintain their health would be helpful in assessing potential threats from
      contaminants in sediment. In a controlled laboratory study the maximum tolerated
      percentage of sediment in the diet of mallards (Anas platyrhynchos) was measured.
      When fed a well-balanced commercial avian diet, 50, 60, or 70% sediment in the
      diet on a dry-weight basis did not cause weight loss over a two-week period.
      Ducks fed this same commercial diet, but containing 80 or 90% sediment, lost 8.6
      and 15.6% of their body weight, respectively, in the first week on those diets.
      After factoring in the ability of the mallards to sieve out some of the sediment
      from their diet before swallowing it, we concluded that the mallards could
      maintain their health even when approximately half of what they swallowed, on a
      dry-weight basis, was sediment.

PMID- 20821614
TI  - Bioaccumulation kinetics of organic xenobiotic pollutants in the freshwater
      invertebrate Gammarus pulex modeled with prediction intervals.
AB  - Uptake and elimination rate constants, bioaccumulation factors, and elimination
      times in the freshwater arthropod Gammarus pulex were measured for 14 organic
      micropollutants covering a wide range of hydrophobicity (imidacloprid, aldicarb,
      ethylacrylate, 4,6-dinitro-o-cresol, carbofuran, malathion, 4-nitrobenzyl
      chloride, 2,4-dichloroaniline, Sea-Nine, 2,4-dichlorophenol, diazinon, 2,4,5
      trichlorophenol, 1,2,3-trichlorobenzene, and hexachlorobenzene; all 14C-labeled).
      The toxicokinetic parameters were determined by least-square fitting of a one
      compartment first-order toxicokinetic model, followed by Markov Chain Monte Carlo
      parameter estimation. The parameter estimation methods used here account for
      decreasing aqueous concentrations during the exposure phase or increasing aqueous
      concentrations during the elimination phase of bioaccumulation experiments. It is
      not necessary to keep exposure concentrations constant or zero during uptake and
      elimination, respectively. Neither is it required to achieve steady state during
      the exposure phase; hence, tests can be shorter. Prediction intervals, which take
      the between-parameter correlation into account, were calculated for
      bioaccumulation factors and simulations of internal concentrations under variable
      exposure. The lipid content of Gammarus pulex was 1.3% of wet weight, consisting
      of 25% phospholipids and 75% triglycerides. Size-dependent bioaccumulation was
      observed for eight compounds, although the magnitudes of the relationships were
      too small to be of practical relevance. Elimination times ranged from 0.45 to 20
      d, and bioaccumulation factors ranged from 1.7 to 4,449 L/kg. The identified
      compounds with unexpectedly long elimination times should be given priority in
      future studies investigating the biotransformation of these compounds.

PMID- 20821615
TI  - Stress response of heavy metal mixture present in wastewater and leachate on heat
      shock protein 47-transfected cells.
AB  - Heavy metals present in water environment and hazardous sites as single compounds
      or mixture may drastically affect human health. In the present work, we
      investigated the risk assessment of wastewater effluents and leachate with a
      focus on three heavy metals-nickel (Ni), cadmium (Cd), and lead (Pb)-and their
      combined effect on mammalian cells, using Chinese hamster ovary cells transfected
      with the heat-shock protein (HSP) 47 promoter. The heavy metal mixture model was
      designed based on the concentrations of metals in wastewater effluents and
      leachate sampled in Tunisia. Using a ternary diagram, we investigated the stress
      response of the interaction model. This research indicated that the single heavy
      metals induced the stress response on HSP(+) cells even at concentrations lower
      than the local and international guidelines. Differences in water quality likely
      influenced the metal responses such that the organic composition of the leachate
      increased the stress response induced by the heavy metals exclusively, whereas
      the effluents included organic compounds that were able to mask the heavy metal
      effect. The mixture characterization discovered the key role played by the high
      levels of Ni or combination of Cd and Pb to induce the highest stress response
      following 3-h incubation. Heat-shock protein 47 has proven its effectiveness for
      assessing the heavy metal mixture effect even at low concentrations. Furthermore,
      the combination of a bioassay system with a statistical model proved extremely
      useful for better understanding the major contributors to the stress response of
      the mixture.

PMID- 20821616
TI  - Occurrence and fate of micropollutants in the Vidy Bay of Lake Geneva,
      Switzerland. Part I: priority list for environmental risk assessment of
      pharmaceuticals.
AB  - Pharmaceuticals are substances designed to have a biological effect in humans.
      Their presence in the environment, especially in surface waters, is of increasing
      concern because of their potential risk to non-target species. A large number of
      pharmaceuticals are on the market; for example, approximately 2,000 active
      ingredients are approved in Europe, and many of them have already been detected
      in surface water. It is therefore crucial to select the substances that may do
      the most harm to the environment prior to performing measurements and extensive
      risk assessment. In the present study, a method to determine a list of
      pharmaceuticals to survey in surface water is proposed. Inclusion of substances
      on the list was based on a screening procedure, the analytical feasibility, and
      previous knowledge of pharmaceuticals detected in water. The screening procedure
      proposed here is an improvement on the standard procedure of the European
      Medicine Evaluation Agency (EMEA). It is designed to decrease the number of
      pharmaceuticals to be evaluated in a stepwise manner, thus decreasing the number
      of data necessary for the evaluation. We applied our approach to determine a list
      of 37 pharmaceuticals and four hormones to survey in a specific region of
      Switzerland, the Lake Geneva area, and discussed the advantages and weak points
      of the method.

PMID- 20821617
TI  - Occurrence and fate of micropollutants in the Vidy Bay of Lake Geneva,
      Switzerland. Part II: micropollutant removal between wastewater and raw drinking
      water.
AB  - The occurrence and removal of 58 pharmaceuticals, endocrine disruptors, corrosion
      inhibitors, biocides, and pesticides, were assessed in the wastewater treatment
      plant (WWTP) of the city of Lausanne, Switzerland, as well as in the effluent
      receiving water body, the Vidy Bay of Lake Geneva. An analytical screening method
      to simultaneously measure all of the 58 micropollutants was developed based on
      ultra performance liquid chromatography coupled to a tandem mass spectrometer
      (UPLC-MS/MS). The selection of pharmaceuticals was primarily based on a
      prioritization study, which designated them as environmentally relevant for the
      Lake Geneva region. Except for the endocrine disruptor 17alpha-ethinylestradiol,
      all substances were detected in 24-h composite samples of wastewater entering the
      WWTP or in the treated effluent. Of these compounds, 40% were also detected in
      raw drinking water, pumped from the lake 3 km downstream of the WWTP. The
      contributions of dilution and degradation to micropollutant elimination between
      the WWTP outlet and the raw drinking water intake were established in different
      model scenarios using hypothetical residence times of the wastewater in Vidy Bay
      of 1, 4, or 90 d. Concentration decrease due to processes other than dilution was
      observed for diclofenac, beta-blockers, several antibiotics, corrosion
      inhibitors, and pesticides. Measured environmental concentrations (MECs) of
      pharmaceuticals were compared to the predicted environmental concentrations
      (PECs) determined in the prioritization study and agreed within one order of
      magnitude, but MECs were typically greater than the corresponding PECs. Predicted
      no-effect concentrations of the analgesic paracetamol, and the two antibiotics
      ciprofloxacin and sulfamethoxazole, were exceeded in raw drinking water samples
      and therefore present a potential risk to the ecosystem.

PMID- 20821618
TI  - Experimental characterization of the mechanism of perfluorocarboxylic acids'
      liver protein bioaccumulation: the key role of the neutral species.
AB  - Perfluorocarboxylic acids (PFCAs) of chain length greater than seven carbon atoms
      bioconcentrate in the livers of fish. However, a mechanistic cause for the
      empirically observed increase in the bioconcentration potential of PFCAs as a
      function of chain length has yet to be determined. To this end, recombinant rat
      liver fatty acid-binding protein (L-FABP) was purified, and its interaction with
      PFCAs was characterized in an aqueous system at pH 7.4. Relative binding
      affinities of L-FABP with PFCAs of carbon chain lengths of five to nine were
      established fluorimetrically. The energetics, mechanism, and stoichiometry of the
      interaction of perfluorooctanoic acid (PFOA) with L-FABP were examined further by
      isothermal titration calorimetry (ITC) and electrospray ionization combined with
      tandem mass spectrometry (ESI-MS/MS). Perfluorooctanoic acid was shown to bind to
      L-FABP with an affinity approximately an order of magnitude less than the natural
      ligand, oleic acid, and to have at least 3:1 PFOA:L-FABP stoichiometry. Two
      distinct modes of PFOA binding to L-FABP were observed by ESI-MS/MS analysis; in
      both cases, PFOA binds solely as the neutral species under typical physiological
      pH and aqueous concentrations of the anion. A comparison of their chemical and
      physical properties with other well-studied biologically relevant chemicals
      showed that accumulation of PFCAs in proteins as the neutral species is
      predictable. For example, the interaction of PFOA with L-FABP is almost identical
      to that of the acidic ionizing drugs ketolac, ibuprofen, and warfarin that show
      specificity to protein partitioning with a magnitude that is proportional to the
      K(OW) (octanol-water partitioning) of the neutral species. The experimental
      results suggest that routine pharmacochemical models may be applicable to
      predicting the protein-based bioaccumulation of long-chain PFCAs.

PMID- 20821619
TI  - Determining the molecular interactions of perfluorinated carboxylic acids with
      human sera and isolated human serum albumin using nuclear magnetic resonance
      spectroscopy.
AB  - Perfluorooctanoate (PFOA) is ubiquitous in North American human sera and has a
      serum half-life of 3.5 years in humans. The molecular interactions that lead to
      the bioaccumulation of these hydrophobic and lipophobic molecules in human blood
      are not well understood. Perfluorohexanoic acid (PFHxA) and PFOA were used as
      model perfluorinated carboxylic acids (PFCAs) to characterize the major site of
      PFCA interaction in human sera. Using novel heteronuclear saturation transfer
      difference nuclear magnetic resonance spectroscopy experiments, human serum
      albumin (HSA) was identified as the major site of interaction for both PFHxA and
      PFOA in human sera. Heteronuclear single quantum coherence nuclear magnetic
      resonance experiments were then performed to interrogate site-specific
      interactions of PFHxA and PFOA with isolated HSA. Perfluorohexanoic acid was
      found to bind specifically to Sudlow's drug-binding site II, whereas PFOA
      interacted preferentially with Sudlow's drug-binding site I at the lower
      concentration, with additional interactions developing at the higher
      concentration. These experiments highlight the utility of nuclear magnetic
      resonance spectrometry as a tool to observe the in situ interactions of chemical
      contaminants with biological systems. Both PFCAs displaced the endogenous HSA
      ligand oleic acid at concentrations lower than observed for the drugs ibuprofen
      and phenylbutazone, which are established HSA ligands. Interactions between PFCAs
      and HSA may affect the pharmacokinetics and distribution of fatty acids and
      certain drugs in the human body and warrant further investigation.

PMID- 20821620
TI  - Fate of fluorotelomer acids in a soil-water microcosm.
AB  - Fluorotelomer carboxylic acids (FTCAs) and the corresponding unsaturated acids
      (FTUCAs) are known intermediates in the biodegradation of industrially produced
      fluorotelomer alcohols (FTOHs) to environmentally persistent perfluorinated
      carboxylic acids (PFCAs). The FTCAs and FTUCAs are of concern for their toxicity,
      reactivity, and unknown disposition in the environment. The fate of these
      compounds was investigated in a simple sediment-water microcosm system.
      Microcosms were spiked with 8:2 FTCA, 10:2 FTCA, 8:2 FTUCA, or 10:2 FTUCA, after
      which sediment and water samples were collected over time and analyzed by liquid
      chromatography-tandem mass spectrometry (LC/MS/MS). The FTCAs and FTUCAs
      investigated in the present study were observed to degrade rapidly, and sorption
      of these analytes to sediment was found to be greater for the 10:2 telomer acids
      compared with the corresponding 8:2 telomer acids. Identifiable degradation
      products of FTCAs and FTUCAs were observed; however, an overall molar balance
      could not be achieved. The observed reactivity and lability of these analytes may
      contribute to the low levels of FTCAs detected in environmental samples.

PMID- 20821621
TI  - pH dependence of binding benzo[h]quinoline and humic acid and effects on
      fluorescence quenching.
AB  - The binding constant (K(DOC)) between humic acid and the nitrogen-containing
      polycyclic aromatic compound (N-PAC), benzo[h]quinoline, was measured at varying
      pH levels using fluorescence quenching (FQ). Because fluorescence characteristics
      of benzo[h]quinoline change with pH, determination required two optimum sets of
      excitation and emission wavelength pairs. A simple mixing model was used to
      eliminate the inherent fluorescence interference between benzo[h]quinoline and
      its protonated form, benzo[h]quinolinium, when estimating binding constants.
      Hydrophobic interaction is likely to control the binding between humic acid and
      benzo[h]quinoline and benzo[h]quinolinium, in lower and higher pH ranges (pH <3,
      pH >6). In contrast, cation exchange seems to control the binding affinity of
      benzo[h]quinolinium in the middle range of pH. The estimates of K(DOC) were up to
      70% smaller after elimination of interference. This indicates that the
      contribution of the minor form influences estimates of the K(DOC)-pH trend for
      benzo[h]quinoline, and potentially explains the large discrepancy reported in the
      literature between results based on using FQ and those based on equilibrium
      dialysis methods. Previous FQ measurements overestimate K(DOC) at some pH values
      and lead to an underestimation of bioavailability in an aquatic environment. The
      application of our models appears to be necessary when using FQ for determining
      the K(DOC)-pH trend for organic compounds with acid-base pair analogs.

PMID- 20821622
TI  - Potential role of sea spray generation in the atmospheric transport of
      perfluorocarboxylic acids.
AB  - The observed environmental concentrations of perfluorooctanoic acid (PFOA) and
      its conjugate base (PFO) in remote regions such as the Arctic have been primarily
      ascribed to the atmospheric transport and degradation of fluorotelomer alcohols
      (FTOHs) and to direct PFO transport in ocean currents. These mechanisms are each
      capable of only partially explaining observations. Transport within marine
      aerosols has been proposed and may explain transport over short distances but
      will contribute little over longer distances. However, PFO(A) has been shown to
      have a very short half-life in aqueous aerosols and thus sea spray was proposed
      as a mechanism for the generation of PFOA in the gas phase from PFO in a water
      body. Using the observed PFO concentrations in oceans of the Northern Hemisphere
      and estimated spray generation rates, this mechanism is shown to have the
      potential for contributing large amounts of PFOA to the atmosphere and may
      therefore contribute significantly to the concentrations observed in remote
      locations. Specifically, the rate of PFOA release into the gas phase from oceans
      in the Northern Hemisphere is calculated to be potentially comparable to global
      stack emissions to the atmosphere. The subsequent potential for atmospheric
      degradation of PFOA and its global warming potential are considered. Observed
      isomeric ratios and predicted atmospheric concentrations due to FTOH degradation
      are used to elucidate the likely relative importance of transport pathways. It is
      concluded that gas phase PFOA released from oceans may help to explain observed
      concentrations in remote regions. The model calculations performed in the present
      study strongly suggest that oceanic aerosol and gas phase field monitoring is of
      vital importance to obtain a complete understanding of the global dissemination
      of PFCAs.

PMID- 20821623
TI  - Bioavailability of hexabromocyclododecane to the polychaete Hediste diversicolor:
      exposure through sediment and food from a contaminated fjord.
AB  - Knowledge of the bioavailability of brominated flame retardants for sediment
      dwelling organisms is limited. The present study investigated bioaccumulation of
      hexabromocyclododecane (HBCD) in the ragworm Hediste diversicolor exposed to
      field-contaminated sediments and food. Sediments and blue mussels (Mytilus
      edulis) were sampled from a fjord on the Norwegian west coast known to be highly
      contaminated with the brominated flame retardant HBCD. During a four-week
      experiment, ragworms were either exposed to sediment containing moderate or high
      concentrations of HBCD, or they were fed contaminated soft tissue from mussel.
      Although mean sediment concentrations were as high as 40 microg/g dry weight in
      the contaminated sediments, no HBCD were detected in the exposed ragworms
      (detection limit up to 2.0 ng/g wet wt). In contrast, the exposure to
      contaminated food (mussel) resulted in elevated body concentrations of 9.1 ng
      HBCD/g wet weight. The partitioning of HBCD in the test-sediments appeared to be
      influenced by the quantity and quality of the sediment organic matter (up to 15%
      total organic carbon). The presence of small plastic beads (<2 mm), which were
      shown to contain a mean of 50 microg/g dry weight of HBCD, could explain the low
      bioavailability of the flame retardant in the sediment. Hexabromocyclododecane in
      food appeared to be readily assimilated in the ragworm, however, and the
      diastereomer pattern indicated a relative increase of alpha-HBCD from mussel to
      ragworm. Hence, in the sampled areas of the fjord, trophic transfer appeared to
      be a more important mechanism for the entry of HBCD into the local benthic food
      web than sediment-to-biota accumulation.

PMID- 20821624
TI  - Toxicity of three binary mixtures to Daphnia magna: comparing chemical modes of
      action and deviations from conceptual models.
AB  - Complex mixtures makes the assessment of environmental hazards difficult due to
      possible antagonistic or synergistic interactions that can occur between
      chemicals, or even more complex effect patterns like dose-level or dose-ratio
      dependent responses. The aim of the present work was to investigate the acute and
      sublethal responses of Daphnia magna Straus exposed to four single chemical
      compounds (imidacloprid, thiacloprid, nickel chloride, and chlorpyrifos) and
      three binary chemical mixtures. In the immobilization and feeding inhibition
      bioassays, chlorpyrifos was the most toxic to D. magna, followed by nickel
      chloride, and imidacloprid and thiacloprid, which showed similar levels of
      toxicity. The MIXTOX was used to evaluate mixture toxicity. Observed data was
      compared with the expected mixture effects predicted by concentration addition
      (CA) and independent action (IA) models; deviations for synergistic/antagonistic
      interactions, dose-level and dose-ratio dependency were also used. In the mixture
      toxicity assessment, several patterns of response were obtained depending on the
      mixture but also on the endpoint tested. For imidacloprid and thiacloprid,
      deviations for synergism were observed in acute exposures (immobilization), and
      antagonism for feeding rates at sublethal concentrations. For imidacloprid and
      chlorpyrifos, antagonism was found in both exposures. In the nickel and
      chlorpyrifos case study, deviations for synergism were observed in the acute
      exposure; a dose-ratio deviation was observed in the feeding inhibition test,
      with a pattern for antagonism, except for where nickel exerts more than 60% of
      the mixture toxicity.

PMID- 20821625
TI  - Influence of the molecular structure and exposure concentration on the uptake and
      elimination kinetics, bioconcentration, and biotransformation of anionic and
      nonionic surfactants.
AB  - In vivo experiments with fish (sole) were performed for pure homologs of linear
      alkylbenzene sulfonates (LAS) and alcohol ethoxylates (AEO), the most widely used
      anionic and nonionic surfactants. The surfactant concentration measured in the
      organism was higher than in the experimental water, and increased with the
      exposure concentration for both compounds. At the exposure levels tested the
      bioconcentration factors (BCF) for AEO were one order of magnitude higher than
      for LAS. Two linear relationships for hydrophobicity were established, one with
      BCF and the other with uptake rate. The influence of the exposure concentration
      on the uptake (k(1)) and elimination (k(2)) velocities was researched. The value
      obtained for k(1) for AEO was higher than for LAS, while k(2) was very similar
      for both compounds, indicating differences in the incorporation and but not in
      the depuration rate. For the first time, internal degradation products of LAS
      were identified and quantified in fish and water and the glucuronic conjugate of
      AEO was detected in an organism. The predominant biotransformation process for
      these compounds may be different: the results suggest a phase I biotransformation
      for LAS and phase II for AEO, due to their different molecular structures.

PMID- 20821626
TI  - Influence of nutrient level on methylmercury content in water spinach.
AB  - Widely consumed vegetables are often cultivated in sewage waters with high
      nutrient levels. They can contain high levels of methylmercury (MeHg), because
      they can form MeHg from inorganic Hg in their young shoots. We determined whether
      the MeHg uptake and the MeHg formation in the shoots of water spinach (Ipomoea
      aquatica) were affected by the presence of a high nutrient level in the growth
      medium. Water spinach shoots were rooted and pretreated in growth medium
      containing 7% (low) or 70% (high) Hoagland nutrient solution; thereafter, the
      plants were treated with either 0.02 microM MeHg or 0.2 microM HgCl2 for 3 d.
      Half the plants were then analyzed for total Hg and MeHg. The remaining plants
      were transferred to mercury-free medium with low or high nutrient levels and
      posttreated for 3 days before analysis of total Hg and MeHg in order to measure
      MeHg formation in the absence of external Hg. The results indicate that nutrient
      level did not influence MeHg uptake, but that a high nutrient level reduced the
      distribution of MeHg to the shoots 2.7-fold versus low nutrient level. After
      treatment with HgCl2, MeHg was found in roots and new shoots but not in old
      shoots. The MeHg:total-Hg ratio was higher in new shoots than in roots, being 13
      times higher at high versus low nutrient levels. Thus, MeHg formation was the
      same in new shoots independent of inorganic Hg concentration, since the total Hg
      level decreased at a high nutrient level.

PMID- 20821627
TI  - Multi-generational effects of polybrominated diphenylethers exposure: embryonic
      exposure of male American kestrels (Falco sparverius) to DE-71 alters
      reproductive success and behaviors.
AB  - Polybrominated diphenylethers (PBDEs) are additive flame-retardants that are
      environmentally persistent and bioaccumulative compounds of particular concern to
      species at high trophic levels, including predatory birds. The developmental
      effects of in ovo exposure to male birds at environmentally relevant levels of
      the PBDE technical mixture, DE-71, on reproductive success and behaviors using
      captive American kestrels (Falco sparverius) were determined. Males were exposed
      in ovo by direct maternal transfer to DE-71 and unintentionally to low
      concentrations of hexabromocyclododecane (HBCD) at three mean +/- standard error
      DE-71 concentrations of 288.60 +/- 33.35 ng/g wet weight (low-exposure), 1130.59
      +/- 95.34 ng/g wet weight (high-exposure), or background levels of 3.01 +/- 0.46
      ng/g wet weight (control). One year following exposure, males were paired with
      unexposed females. Reproductive success was lower in the high exposure pairs: 43%
      failed to lay eggs while all other pairs laid complete clutches; they also laid
      smaller clutches and produced smaller eggs with reduced fertility, parameters
      that were negatively correlated with paternal in ovo concentrations of all PBDEs,
      as well as individual congeners and HBCD. Throughout courtship, there were fewer
      copulations by all in ovo exposed males, fewer mate-calls made by high-exposure
      males, and decreasing trends in pair-bonding and nest-box behaviors across
      treatments that continued during brood rearing. The reductions in clutch size and
      fertility were associated with the reduced frequencies of male courtship
      behaviors, and were associated with increasing concentrations of the PBDE
      congeners BDE-47, -99, -100, -53, -138, and HBCD. The results of the present
      study confirm effects noted in the F(0) generation and demonstrate that exposure
      to DE-71 affects multiple generations of this predatory avian species at
      environmentally relevant levels of exposure.

PMID- 20821628
TI  - Long-term trends in liver neoplasms in brown bullhead in the Buffalo River, New
      York, USA.
AB  - The Buffalo River area of concern (AOC) was assigned an impaired status for the
      fish tumors and other deformities beneficial use impairment category by the New
      York State Department of Environmental Protection in 1989. This was initially
      based on an inadequately documented brown bullhead (Ameiurus nebulosus) feeding
      study using river sediment extracts. The presence of liver tumors was
      subsequently supported by reports of a 19 to 27% prevalence in wild brown
      bullhead between 1983 and 1988 and a 4.8% prevalence in 1998. However, neither
      fish size (or age) nor sample locations were given, and histopathological
      definitions were inconsistent in these previous studies. Therefore, in 2008, we
      re-evaluated the prevalence of hepatocellular and chloangiocellular tumors (as
      well as other gross indicators of fish health) in brown bullhead averaging 25 cm
      in length collected from three reaches of the Buffalo River and recorded our
      collection sites by global positioning system. Among the 37 fish of appropriate
      size collected, only three exhibited liver tumors (8%). The tumors were evenly
      distributed within the three reaches, and only hepatocellular tumors were found.
      There were no differences in the prevalence of hepatic foci of alteration, body
      weight, length, or hepatosomatic index among the three reaches, but the
      conditions factor was significantly lower in fish from reach 2. Natural
      attenuation of water and sediment quality are the most likely causes for the
      decrease in liver tumors. The prevalence of liver tumors between 1998 and 2008 in
      the Buffalo River is similar to that found in recovery-stage AOCs and some Great
      Lakes reference areas.

PMID- 20821629
TI  - Metal (As, Cd, Hg, and CH3Hg) bioaccumulation from water and food by the benthic
      amphipod Leptocheirus plumulosus.
AB  - Benthic invertebrates may be exposed to metals in pore water, overlying water,
      ingested sediments, and other food particles. Rates and routes of metal exposure
      have important implications for predicting toxicity and interpreting toxicity
      test results. For the standard test amphipod Leptocheirus plumulosus, radiotracer
      techniques were used to quantify rates of Cd, As, Hg(II), and CH(3)Hg
      bioaccumulation from water and from suspension feeding on labeled microalgae.
      Measured parameters were incorporated into a bioaccumulation model to predict
      steady-state metal concentrations in L. plumulosus and to evaluate the relative
      importance of aqueous and dietary uptake pathways across a range of ingested
      particle types and ingestion rates. Results indicate that ingested particles
      contribute strongly to metal bioaccumulation and that feeding plasticity could
      strongly influence metal exposure. As L. plumulosus switches from suspension
      feeding to deposit feeding or selectively feeds on particles for which it has a
      high assimilation efficiency, metal exposure and body burden will increase. At
      ingestion rates previously reported for deposit feeding (3 g/g/d), dietary metal
      sources dominate metal bioaccumulation and can be responsible for greater than
      90% of metal bioaccumulated, regardless of metal partitioning or ingested
      particle type. These results suggest that more research on L. plumulosus feeding
      behavior is needed to produce a more complete mechanistic understanding of metal
      bioaccumulation.

PMID- 20821630
TI  - Mercury contamination of the fish community of a semi-arid and arid river system:
      spatial variation and the influence of environmental gradients.
AB  - Mercury (Hg) contamination of aquatic ecosystems is a global environmental
      problem. Data are abundant on Hg contamination and factors that affect its
      bioaccumulation in lake communities, but comparatively little information on
      riverine ecosystems exists. The present study examines fish Hg concentrations of
      the Lower Rio Grande/Rio Bravo del Norte drainage, Texas, USA and several of its
      major tributaries in order to assess whether spatial variation occurs in fish Hg
      concentrations in the drainage and if patterns of Hg contamination of fish are
      related to gradients in environmental factors thought to affect Hg concentrations
      in fish communities. Fish, invertebrates, sediments, and water quality parameters
      were sampled at 12 sites along the lower Rio Grande/Rio Bravo del Norte drainage
      multiple times over a one-year period. Spatial variation was significant in fish
      Hg concentrations when fish were grouped by literature-defined trophic guilds or
      as stable isotope-defined trophic levels, with highest concentrations found in
      the Big Bend region of the drainage. Mercury in fish in most trophic guilds and
      trophic levels were positively related to environmental factors thought to affect
      Hg in fish, including water column dissolved organic carbon (DOC) and sediment Hg
      concentrations. It is likely that fish Hg concentrations in the Big Bend region
      are relatively high because this section of the river has abundant geologic Hg
      sources and environmental conditions which may make it sensitive to Hg inputs
      (i.e., high DOC, variable water levels). Results from the present study indicate
      that Hg contamination of the Rio Grande/Rio Bravo del Norte has substantial
      implications for management and protection of native small-bodied obligate
      riverine fish, many of which are imperiled.

PMID- 20821631
TI  - Combining rapid bioassessment and field-based microcosms for identifying impacts
      in an urban river.
AB  - Rapid bioassessment indices based on macroinvertebrates are the most commonly
      used tools for assessing stream condition. However, once stream degradation has
      been detected, it is often difficult to identify which environmental stressors
      are most important because of changes in multiple correlated factors. In this
      study, we examined eight sites in an urban river watershed using a field-based
      microcosm experiment and the rapid bioassessment-based biotic index, SIGNAL. The
      experiment assessed the effects of polluted river sediment by examining the
      macroinvertebrate taxa that colonized sediments at an unpolluted wetland. Results
      were compared with an assessment of field-collected macroinvertebrates using
      SIGNAL, a biotic index that assigns pollution sensitivity scores to
      macroinvertebrate families, and environmental data, to determine whether sediment
      pollution or other factors such as habitat deterioration were likely to be
      influencing riverine macroinvertebrate communities. The microcosm results
      indicated that common species (Tanytarsus fuscithorax, Procladius paludicola, and
      Ablabesmyia notabilis) and the overall macroinvertebrate assemblage did not
      significantly change among sediments from different sites, with the exception of
      local effects on a few uncommon taxa (Chironomus pseudoppositus, Kiefferulus
      martini, Cladotanytarsus australomancus, Chaoboridae, Polypedilum "S1," and
      Tanytarsus belairensis). In contrast, SIGNAL showed a gradual trend of
      deterioration from upstream to downstream, decreasing from a score of 6.5 in
      upstream areas (unimpacted) to a score of 4.4 in the downstream sites (moderately
      impacted). This result combined with a significant correlation of SIGNAL scores
      to habitat data suggested that habitat deterioration rather than polluted
      sediment was likely to be responsible for the declining stream condition detected
      with the rapid bioassessment approach. The addition of the microcosms to other
      monitoring approaches could be useful for determining whether sediment pollution
      is influencing degraded urban streams.

PMID- 20821632
TI  - Effects of suspended solids and dissolved organic carbon on nickel toxicity.
AB  - Nickel (Ni) is a common and potentially toxic heavy metal in many fluvial
      ecosystems. We examined the potentially competitive and complementary roles of
      suspended sediment and a dissolved organic ligand, humate, in affecting the
      partitioning and toxicity of Ni to a model organism, Daphnia magna, in both batch
      and stream-recirculating flume (SRF) tests. Sediments included a fine-grained
      deposit, montmorillonite, and kaolinite. Survival of D. magna was unaffected by
      the range of suspended solids used in the present study (8-249 mg/L). However,
      exposure to suspended solids that were amended with Ni had a deleterious effect
      on test organism survival, which is attributed to partitioning of Ni into the
      aqueous phase. At comparable levels of dissolved Ni, survival of D. magna was
      reduced in tests with Ni-amended suspended solids compared to Ni-only aqueous
      exposures, suggesting potentiation between these two aquatic contaminants.
      Addition of humate attenuated toxicity to D. magna in both Ni-only and Ni-amended
      suspended sediment exposures. These results indicate that organic ligands and
      suspended solids have important functions in affecting the bioavailability and
      toxicity of Ni to aquatic organisms and should be incorporated into predictive
      models to protect ecosystem quality.

PMID- 20821633
TI  - Embryo malposition as a potential mechanism for mercury-induced hatching failure
      in bird eggs.
AB  - We examined the prevalence of embryo malpositions and deformities in relation to
      total mercury (THg) and selenium (Se) concentrations in American avocet
      (Recurvirostra americana), black-necked stilt (Himantopus mexicanus), and
      Forster's tern (Sterna forsteri) eggs in San Francisco Bay (CA, USA) during 2005
      to 2007. Overall, 11% of embryos were malpositioned in eggs > or =18 d of age (n
      = 282) and 2% of embryos were deformed in eggs > or =13 d of age (n = 470).
      Considering only those eggs that failed to hatch (n = 62), malpositions occurred
      in 24% of eggs > or =18 d of age and deformities occurred in 7% of eggs > or =13
      d of age. The probability of an embryo being malpositioned increased with egg THg
      concentrations in Forster's terns, but not in avocets or stilts. The probability
      of embryo deformity was not related to egg THg concentrations in any species.
      Using a reduced dataset with both Se and THg concentrations measured in eggs (n =
      87), we found no interaction between Se and THg on the probability of an embryo
      being malpositioned or deformed. Results of the present study indicate that
      embryo malpositions were prevalent in waterbird eggs that failed to hatch and the
      likelihood of an embryo being malpositioned increased with egg THg concentrations
      in Forster's terns. We hypothesize that malpositioning of avian embryos may be
      one reason for mercury-related hatching failure that occurs late in incubation,
      but further research is needed to elucidate this potential mechanism.

PMID- 20821634
TI  - Telemetry-based field studies for assessment of acute and short-term risk to
      birds from spray applications of chlorpyrifos.
AB  - In a program of avian field studies, radiotelemetry was combined with
      observations, carcass searches, residue analysis, and determination of brain
      acetylcholinesterase (AChE) activity to assess the acute and short-term risk
      posed by chlorpyrifos to birds. Studies were conducted in field crops (brassicas,
      Poland) and orchards (pome, Italy; citrus, Spain). In total, 25 individual
      applications of chlorpyrifos were studied on 13 sites. Before each application,
      birds were fitted with radio transmitters (with minimum stress to birds).
      Radiotagged birds were monitored and the avifauna observed before, during and for
      7 d following each application. A total of 201 birds representing 19 species were
      radiotagged. In 80% of individual telemetric monitoring periods, birds remained
      at the study sites. No radiotagged birds showed any sign of intoxication. These
      included individuals who spent a major proportion of time within treated areas
      (some individuals located within treated area on >90% of occasions). A total of
      7,238 bird sightings were recorded during constant observation during and
      immediately after application. An additional 4,017 sightings were recorded in 104
      individual surveys during 7 d after each application. Two untagged birds (out of
      11,255 bird sightings) exhibited atypical behavior for <1 min and 2 to 3 min,
      respectively, before flying away. This observation (for 0.02% of bird sightings)
      may or may not have been treatment related. Ten carcasses were recovered (none
      radiotagged). Residue analysis and brain AChE activity indicated that none was
      likely to have died from chlorpyrifos exposure. Radiotracking, supported by more
      traditional assessment methods, was effective for assessing impacts in the field.
      This extensive field program supports a conclusion that spray applications of
      chlorpyrifos present a low risk to birds.

PMID- 20821635
TI  - Preexposure to ultraviolet B radiation and 4-tert-octylphenol affects the
      response of Rana pipiens tadpoles to 3,5,3'-triiodothyronine.
AB  - Exposure to multiple environmental stressors is negatively impacting the health
      of amphibians worldwide. Increased exposure to ultraviolet B radiation (UVBR) and
      chemical pollutants may affect amphibian populations by disrupting metamorphosis;
      however, the actual mechanisms by which these stressors affect development remain
      unknown. Because amphibian metamorphosis is controlled by thyroid hormones (TH),
      changes in developmental rates by environmental stress suggest a disruption of
      the thyroid system. Tadpoles were chronically exposed to environmental levels of
      UVBR (average of 0.15 W/m2) and 4-tert-octylphenol (OP; 10 nM), alone and
      combined, prior to being challenged to exogenous TH triiodothyronine (T3; 5 or 50
      nM). This experimental approach was taken to determine whether exposure to these
      stressors affects the ability of T3 to elicit specific molecular and
      morphological responses. Exposure to OP increased mRNA levels of thyroid
      receptors (TRs) alpha and beta, deiodinase type 2 (D2), and corticotropin
      releasing hormone in the brain and of D2 in the tail of tadpoles. 4-tert
      octylphenol also enhanced T3-induced expression of D2 in the brain. The
      combination of UVBR and OP affected the expression of TR alpha in the brain and
      the responses of TR alpha and beta genes to T3 in the tail, demonstrating the
      importance of considering the effects of multiple stressors on amphibians.
      Tadpoles exposed to UVBR were developmentally delayed and exhibited slowed tail
      resorption and accelerated hindlimb development following exposure to T3.
      Together, these findings indicate that UVBR alters the rate of development and TH
      dependent morphological changes at metamorphosis, and that exposure to UVBR
      and/or OP disrupts the expression of genes important for development and the
      biological action of T3 in peripheral tissues. Our group is the first to
      demonstrate that environmental levels of UVBR and/or OP can affect the thyroid
      system of amphibians.

PMID- 20821636
TI  - Acute toxicity of emamectin benzoate and its desmethyl metabolite to Eohaustorius
      estuarius.
AB  - Emamectin benzoate is one of the active ingredients of the anti-sealice drug
      SLICE. Ten-day acute sediment lethal tests (10-d LC50) of emamectin benzoate and
      its desmethyl metabolite (AB1) were conducted to determine LC50 values using a
      sensitive representative West Coast amphipod crustacean, Eohaustorius estuarius.
      The 10-d LC50s of emamectin benzoate and AB1 to E. estuarius were 0.185 and 0.019
      mg/kg wet weight sediment (0.146 and 0.015 mg/kg dry wt), respectively. The
      degradation properties of emamectin benzoate and AB1 during the 10-d period were
      also measured and described. No obvious decay patterns were observed for either
      emamectin benzoate and AB1 over the 10-d period.

PMID- 20821637
TI  - Determining the influence of rainfall patterns and carbendazim on the surface
      activity of the earthworm Lumbricus terrestris.
AB  - Carbendazim is highly toxic to earthworms and is used as a standard control
      substance when running field-based trials of pesticides, but results using
      carbendazim are highly variable. In the present study, impacts of timing of
      rainfall events following carbendazim application on earthworms were
      investigated. Lumbricus terrestris were maintained in soil columns to which
      carbendazim and then deionized water (a rainfall substitute) were applied.
      Carbendazim was applied at 4 kg/ha, the rate recommended in pesticide field
      trials. Three rainfall regimes were investigated: initial and delayed heavy
      rainfall 24 h and 6 d after carbendazim application, and frequent rainfall every
      48 h. Earthworm mortality and movement of carbendazim through the soil was
      assessed 14 d after carbendazim application. No detectable movement of
      carbendazim occurred through the soil in any of the treatments or controls.
      Mortality in the initial heavy and frequent rainfall was significantly higher
      (approximately 55%) than in the delayed rainfall treatment (approximately 25%).
      This was due to reduced bioavailability of carbendazim in the latter treatment
      due to a prolonged period of sorption of carbendazim to soil particles before
      rainfall events. The impact of carbendazim application on earthworm surface
      activity was assessed using video cameras. Carbendazim applications significantly
      reduced surface activity due to avoidance behavior of the earthworms. Surface
      activity reductions were least in the delayed rainfall treatment due to the
      reduced bioavailability of the carbendazim. The nature of rainfall events'
      impacts on the response of earthworms to carbendazim applications, and details of
      rainfall events preceding and following applications during field trials should
      be made at a higher level of resolution than is currently practiced according to
      standard International Organization for Standardization protocols.

PMID- 20821638
TI  - Functional behavior and reproduction in androgenic sex reversed zebrafish (Danio
      rerio).
AB  - Endocrine-disrupting chemicals released into natural watercourses may cause
      biased sex ratios by sex reversal in fish populations. The present study
      investigated the androgenic sex reversal of zebrafish (Danio rerio) exposed to
      the androgenic compound 17beta-trenbolone (TB) and whether sex-changed females
      would revert to the female phenotype after cessation of TB exposure. 17beta
      Trenbolone is a metabolite of trenbolone acetate, an anabolic steroid used as a
      growth promoter in beef cattle. 17beta-Trenbolone in runoff from cattle feedlots
      may reach concentrations that affect fish sexual development. Zebrafish were
      exposed to a concentration of 20 ng/L TB in a flow-through system for five months
      from egg until sexual maturity. This resulted in an all-male population. It was
      further found that all these phenotypic males displayed normal male courtship
      behavior and were able to reproduce successfully, implying that the sex reversal
      was complete and functional. None of the phenotypic males developed into females
      after six months in clean water, demonstrating that androgenic sex reversal of
      zebrafish is irreversible.

PMID- 20821639
TI  - Acute copper toxicity in the euryhaline copepod Acartia tonsa: implications for
      the development of an estuarine and marine biotic ligand model.
AB  - Copepods (Acartia tonsa) were exposed (48 h) to waterborne, diet-borne (non-Cu
      equilibrated and Cu-equilibrated food), and waterborne plus diet-borne Cu in
      either the absence or the presence of food (diatom Thalassiosira weissflogii).
      Toxicity tests were run in different salinities (5, 15, and 30 ppt) together with
      measurements of physicochemical parameters and total and dissolved Cu
      concentrations in the experimental media. Results show that most of the toxic Cu
      fraction was in the dissolved phase. In general, Cu toxicity was higher in low (5
      ppt) than in high salinity (30 ppt), regardless of the pathway of Cu exposure
      tested. In the absence of food, data clearly indicate that differences in
      waterborne Cu toxicity can be explained by changes in water chemistry. However,
      addition of food (either non-Cu-equilibrated or Cu-equilibrated) to the
      experimental media protected against acute Cu toxicity in salinities 5 and 15
      ppt, suggesting that A. tonsa requires extra energy to cope with the stressful
      condition imposed by Cu exposure associated with the ionoregulatory requirements
      in low salinities. For diet-borne exposure, a very high Cu concentration was
      necessary to precontaminate the diatoms to a level resulting in copepod
      mortality. Therefore, availability of food exerted a more important positive
      impact in protecting against acute Cu toxicity than its potential negative impact
      via contamination resulting in toxicity. Findings indicate the need for
      incorporation of both salinity and food in a future biotic ligand model (BLM)
      version for Cu in estuarine and marine waters. In this context, the euryhaline
      copepod A. tonsa would be a suitable model species with which to perform
      experiments to validate and calibrate any future saltwater BLM.

PMID- 20821640
TI  - Subcellular distribution of zinc in Daphnia magna and implication for toxicity.
AB  - We examined the subcellular partitioning of zinc (Zn) in Daphnia magna both under
      acute and chronic exposures. In the acute Zn toxicity tests, the daphnids were
      exposed to different Zn concentrations for 48 h or to one lethal concentration
      (1,000 microg/L) for different durations (time to death for up to 47 h).
      Significant mortality of daphnids was observed when the newly accumulated Zn
      concentration reached a threshold level of approximately 40 microg/g wet weight
      (or 320 microg/g dry wt), approximately 3.5 times higher than the background
      tissue concentration (92 microg/g dry wt). Chronic exposure (14 d) to Zn resulted
      in nonobservable effect on survivorship and growth at newly accumulated tissue
      concentration of over 40 microg/g wet weight. With increasing Zn acute exposure,
      more Zn was partitioned into the cellular debris fraction, indicating that this
      fraction was presumably the first targeted site of binding for Zn upon entering
      the animals. The importance of other subcellular fractions either decreased
      accordingly or remained comparable. We found that the metal-sensitive fraction
      (Zn distribution in the organelles and heat-denatured proteins) did not predict
      the acute Zn toxicity in Daphnia. During chronic exposure, however, no major
      change of the subcellular partitioning of Zn with increasing Zn exposure was
      documented. Zinc was mainly found in the organelles and heat-stable protein
      fractions during chronic exposure, suggesting that any subcellular repartitioning
      occurred primarily during acute exposure. Metallothioneins were induced upon
      chronic Zn exposure, but its induction evidently lagged behind the Zn
      accumulation. Our present study showed that the subcellular fractionation
      approach could not be readily used to predict the acute and chronic toxicities of
      Zn in Daphnia. A tissue-based Zn accumulation approach with a threshold Zn tissue
      concentration was better in predicting acute Zn toxicity.

PMID- 20821641
TI  - Influence of selected antibiotics on the response of black fly (Simulium
      vittatum) larvae to insecticidal proteins produced by Bacillus thuringiensis
      subsp. israelensis.
AB  - A controlled current toxicity test (CCTT) was developed to evaluate the response
      of black fly (Simulium vittatum) larvae to insecticidal proteins following
      exposure to various antibiotics. The bacterium, Bacillus thuringiensis subsp.
      israelensis (Bti), produces proteins that are toxic to Nemotoceran Diptera, such
      as black flies and mosquitoes, when ingested. These insecticidal crystalline
      proteins (ICPs) are highly efficacious in controlling black flies; however,
      speculation has arisen regarding the potential for antibiotic contamination of
      waterways to mitigate the toxicity of these proteins. A series of experiments was
      conducted with the CCTT in which black fly larvae were exposed to enrofloxacin,
      tylosin, sulfamethoxazole, and trimethoprim followed by exposure to Bti ICPs.
      These antibiotics were selected based on their use in agricultural and documented
      anthropogenic contamination of rivers. Anthropogenic concentrations of a mixture
      of these four antibiotics did not affect the response of the larvae to Bti ICPs.
      Subsequent experiments were conducted with antibiotic concentrations 10,000 to
      80,000 times higher than those found in contaminated rivers. Exposure of black
      fly larvae to high levels of enrofloxacin (0.5 mg/L) had no effect upon the
      susceptibility to Bti ICPs; however, exposure to high levels of tylosin (8 mg/L)
      resulted in a significant increase in the susceptibility of the larvae to Bti
      ICPs at 72 h of exposure, but not at 48 h. Exposure of black fly larvae to high
      concentrations of a mixture of sulfamethoxazole and trimethoprim resulted in a
      significant increase in the efficacy of the larvicide after 48 and 72 h of
      exposure. These results suggest that impairment of the efficacy of Bti ICPs to
      black fly larvae is not due to antibiotic contamination of the larval
      environment.

PMID- 20821642
TI  - A physiologically based toxicokinetic model for methylmercury in female American
      kestrels.
AB  - A physiologically based toxicokinetic (PBTK) model was developed to describe the
      uptake, distribution, and elimination of methylmercury (CH(3)Hg) in female
      American kestrels. The model consists of six tissue compartments corresponding to
      the brain, liver, kidney, gut, red blood cells, and remaining carcass. Additional
      compartments describe the elimination of CH(3)Hg to eggs and growing feathers.
      Dietary uptake of CH(3)Hg was modeled as a diffusion-limited process, and the
      distribution of CH(3)Hg among compartments was assumed to be mediated by the flow
      of blood plasma. To the extent possible, model parameters were developed using
      information from American kestrels. Additional parameters were based on measured
      values for closely related species and allometric relationships for birds. The
      model was calibrated using data from dietary dosing studies with American
      kestrels. Good agreement between model simulations and measured CH(3)Hg
      concentrations in blood and tissues during the loading phase of these studies was
      obtained by fitting model parameters that control dietary uptake of CH(3)Hg and
      possible hepatic demethylation. Modeled results tended to underestimate the
      observed effect of egg production on circulating levels of CH(3)Hg. In general,
      however, simulations were consistent with observed patterns of CH(3)Hg uptake and
      elimination in birds, including the dominant role of feather molt. This model
      could be used to extrapolate CH(3)Hg kinetics from American kestrels to other
      bird species by appropriate reassignment of parameter values. Alternatively, when
      combined with a bioenergetics-based description, the model could be used to
      simulate CH(3)Hg kinetics in a long-term environmental exposure.

PMID- 20821643
TI  - Consequences of stressor-induced changes in species assemblage for biodiversity
      indicators.
AB  - Protection of biodiversity is a major objective in environmental management.
      However, standard protocols for ecological risk assessments use endpoints that
      are not directly related to biodiversity. In the present study, the changes in
      five biodiversity indicators, namely, the Hill, Shannon-Wiener, Simpson's
      diversity index, AZTI's Marine Benthic Index (AMBI), and Benthic Quality Index
      (BQI), are calculated in case species experience direct chemical effects. This is
      done for an uncontaminated situation as well as for situations in which the
      effect concentration of a certain fraction of species (x%) is exceeded, that is,
      at the hazardous concentration (HCx) of the species sensitivity distribution
      (SSD) of the considered community. Results indicate that the response of the
      biodiversity indicators to concentrations spanning the complete concentration
      range of the SSD is variable. This response depends mainly on the type of
      indicator, the species assemblage, and the ratio of the slope of the
      concentration effect curves of the species and the slope of the SSD. At the HC5,
      a commonly used threshold in environmental risk assessment, biodiversity
      indicators, are affected at a marginal level (change is less than 5% in 99.6% of
      the simulated cases). Based on the results, the HC5 level is likely to be a
      protective threshold for changes in biodiversity in terms of richness and
      heterogeneity in the vast majority of the simulated cases (99.6%) for chemicals
      for which direct effects are dominant.

PMID- 20821644
TI  - Occurrence of synthetic musk fragrances in human blood from 11 cities in China.
AB  - We measured two nitro musk fragrances (musk xylene) and musk ketone) and five
      polycyclic musk fragrances (galaxolide [HHCB], tonalide [AHTN], celestolide
      [ADBI], traseolide [ATII], and phantolide [AHMI]) in human blood samples from 11
      cities of China (n = 204). Possible temporal trends in musk concentrations and
      associations with personal factors, such as gender, age, and others, were
      studied. Galaxolide (HHCB) showed the highest median concentration (0.85 ng/g)
      followed by AHTN (0.53 ng/g) with high detection frequency (91 and 77%,
      respectively). Concentrations of the other synthetic musk fragrances, including
      musk ketone and musk xylene, were all below the quantification limits. The
      results suggested that musk concentrations were not significantly relative to
      gender and body weight but positively correlated with age groups and locations.
      Apparent differences were also observed in the ratios of HHCB to AHTN
      concentrations among different cities.

PMID- 20821645
TI  - Evaluation of sorbent amendments for in situ remediation of metal-contaminated
      sediments.
AB  - The present study evaluated sorbent amendments for in situ remediation of
      sediments contaminated with two divalent metals. A literature review screening
      was performed to identify low-cost natural mineral-based metal sorbents and high
      performance commercial sorbents that were carried forward into laboratory
      experiments. Aqueous phase metal sorptivity of the selected sorbents was
      evaluated because dissolved metals in sediment porewater constitute an important
      route of exposure to benthic organisms. Based on pH-edge sorption test results,
      natural sorbents were eliminated due to inferior performance. The potential as in
      situ sediment amendment was explored by comparing the sorption properties of the
      engineered amendments in freshwater and saltwater (10 PPT salinity estuarine
      water) matrices. Self-assembled monolayers on mesoporous supports with thiols
      (Thiol-SAMMS) and a titanosilicate mineral (ATS) demonstrated the highest
      sorption capacity for cadmium (Cd) and lead (Pb), respectively. Sequential
      extraction tests conducted after mixing engineered sorbents with contaminated
      sediment demonstrated transfer of metal contaminants from a weakly bound state to
      a more strongly bound state. Biouptake of Cd in a freshwater oligochaete was
      reduced by 98% after 5-d contact of sediment with 4% Thiol-SAMMS and sorbed Cd
      was not bioavailable. While treatment with ATS reduced the small easily
      extractable portion of Pb in the sediment, the change in biouptake of Pb was not
      significant because most of the native lead was strongly bound. The selected
      sorbents added to sediments at a dose of 5% were mostly nontoxic to a range of
      sensitive freshwater and estuarine benthic organisms. Metal sorbent amendments in
      conjunction with activated carbon have the potential to simultaneously reduce
      metal and hydrophobic contaminant bioavailability in sediments.

PMID- 20821646
TI  - Environmental factors affecting the levels of legacy pesticides in the airshed of
      Delaware and Chesapeake Bays, USA.
AB  - Organochlorine insecticides and their degradation products contribute to toxicity
      in Chesapeake Bay, USA, sediments and affect the reproductive health of avian
      species in the region; however, little is known of atmospheric sources or
      temporal trends in concentrations of these chemicals. Weekly air (n = 265) and
      daily rain samples (n = 494) were collected over 2000 to 2003 from three
      locations in the Delmarva Peninsula, USA. Pesticides were consistently present in
      the gas phase with infrequent detection in the particle phase.
      Hexachlorocyclohexanes (HCHs) and cis- and trans-chlordane were detected most
      frequently (95-100%), and cis- and trans-nonachlor, oxychlordane, heptachlor,
      heptachlor epoxide, dieldrin, and 1-chloro-4-[2,2-dichloro-1-(4
      chlorophenyl)ethenyl]benzene (4,4'-DDE) were also detected frequently. The
      highest mean air concentrations were for dieldrin (60-84 pg/m(3)), gamma-HCH (37
      83 pg/m(3)), and 4,4'-DDE (16-80 pg/m(3)). Multiple regression analyses of air
      concentrations with temperature and wind conditions using modified Clausius
      Clapeyron equations explained only 30 to 60% of the variability in concentration
      for most chemicals. Comparison of the air concentrations and enthalpy of air
      surface exchange values at the three sites indicate sources of chlordanes and
      alpha-HCH sources are primarily from long-range transport. However, examination
      of chlordane isomer ratios indicates some local and regional contributions, and
      gamma-HCH, 4,4'-DDE, dieldrin, heptachlor, heptachlor epoxide, and oxychlordane
      also have local or regional sources, possibly from contaminated soils. Median
      rain sample volumes of 1 to 3 L led to infrequent detections in rain; however,
      average measured concentrations were 2 to 10 times higher than in the Great
      Lakes. Dissipation half-lives in air were well below 10 years for all chemicals
      and below published values for the Great Lakes except dieldrin, which did not
      decline during the sample period.

PMID- 20821647
TI  - Environmental impact of insecticides applied on biotech soybean crops in relation
      to the distance from aquatic ecosystems.
AB  - Aquatic environments located in areas cultivated with biotech soybean were
      studied. Water and sediment samples were analyzed for insecticides, acute
      toxicity, genotoxicity, detoxification biomarkers, and fish diversity. Samples
      were taken in the core area of soybean cultivation in Argentina; all measures
      were related to the distance between the crops and the streams sampled.
      Endosulfan (alpha + beta) concentrations as high as 553.33 microg/kg were found
      in sediments from environments located at 0.15 m from treated fields.
      Ethoxyresorufin-O-deethylase (EROD) activity and cytochrome P4501A1 (CYP1A1) gene
      expression in fish showed the highest correlation with the environmental
      concentration of endosulfan. These biomarkers and mortality of amphipods
      significantly correlated with the concentration of endosulfan in water and
      sediment, which correlates inversely with the distance between the crop and
      streams. The differences with respective controls disappear at distances greater
      than 5 m. The fish diversity was significantly lower from distances between the
      margin of the stream and soybean crops, not exceeding 2 m.

PMID- 20821648
TI  - Toxic hazard and chemical analysis of leachates from furfurylated wood.
AB  - The furfurylation process is an extensively investigated wood modification
      process. Furfuryl alcohol molecules penetrate into the wood cell wall and
      polymerize in situ. This results in a permanent swelling of the wood cell walls.
      It is unclear whether or not chemical bonds exist between the furfuryl alcohol
      polymer and the wood. In the present study, five different wood species were
      used, both hardwoods and softwoods. They were treated with three different
      furfurylation procedures and leached according to three different leaching
      methods. The present study shows that, in general, the leachates from
      furfurylated wood have low toxicity. It also shows that the choice of leaching
      method is decisive for the outcome of the toxicity results. Earlier studies have
      shown that leachates from wood treated with furfuryl alcohol prepolymers have
      higher toxicity to Vibrio fischeri than leachates from wood treated with furfuryl
      alcohol monomers. This is probably attributable to differences in leaching of
      chemical compounds. The present study shows that this difference in the toxicity
      most likely cannot be attributed to maleic acid, furan, furfural, furfuryl
      alcohol, or 2-furoic acid. However, the difference might be caused by the two
      substances 5-hydroxymethylfurfural and 2,5-furandimethanol. The present study
      found no difference in the amount of leached furfuryl alcohol between leachates
      from furfurylated softwood and furfurylated hardwood species. Earlier studies
      have indicated differences in grafting of furfuryl alcohol to lignin. However,
      nothing was found in the present study that could support this. The leachates of
      furfurylated wood still need to be

PMID- 20821649
TI  - Retention-release characteristics of triclocarban and triclosan in biosolids,
      soils, and biosolids-amended soils.
AB  - Transport models that incorporate retention/release characteristics of organic
      compounds in soils and sediments typically assume that organic-carbon normalized
      partition coefficients (K(OC)) apply to all solid matrices and that the
      partitioning process is completely reversible. Partition coefficients (K(d))
      (from which the K(OC) was calculated), and retention/release characteristics of
      triclocarban (TCC) and triclosan (TCS) in biosolids, soils, and biosolids-amended
      soils were determined. Four soils of different physicochemical properties amended
      with biosolids at 10 g/kg, together with unamended soils, and several biosolids
      were separately spiked with either [(14)C]TCC or [(14)C]TCS for the various
      determinations. The hysteresis coefficient values of the two compounds were
      consistently <1 in all three solid matrices, suggesting strong hysteresis.
      Multiple desorption steps (24 h each) over several days revealed incomplete
      desorption of the two compounds from all three solid matrices. The K(d) values
      determined in biosolids (log K(d) 3.34 +/- 0.13 for TCC and 3.76 +/- 0.39 for
      TCS) were greater than those determined in soils (log K(d) 1.71 +/- 0.09 for TCC
      and 2.25 +/- 0.26 for TCS) and biosolids-amended soils (log K(d)1.90 +/- 0.16 for
      TCC and 2.31 +/- 0.19 for TCS), however, the K(OC) values of all three solid
      matrices were similar (log K(OC) of 3.82 +/- 0.16 for TCC and 4.26 +/- 0.31 for
      TCS). Thus, it was concluded that a single or a narrow range of K(OC) values for
      TCC and TCS may be appropriate to describe retention of the compounds in soils
      and sediments. However, models that assume complete reversibility of the
      retention/release processes of the compounds in soils and sediments may not
      adequately describe the retention/release characteristics of the compounds in
      soils and sediments, especially when the chemicals are biosolids borne.

PMID- 20821650
TI  - Tetracycline sorption to coal and soil humic acids: an examination of humic
      structural heterogeneity.
AB  - The sorption properties of tetracycline were compared between a coal humic acid
      (CHA) and a soil humic acid (SHA) under various solution chemistry conditions.
      Structural characteristics of the two humic acids were quantified in detail by
      elemental analysis, solid-state (13)C nuclear magnetic resonance (NMR), acid-base
      titration, and Zeta potential measurement. The CHA consists primarily of
      poly(methylene)-rich aliphatics with more aromatic C--O and higher negative
      surface charge, while SHA is mainly composed of young material residues of
      lignin, carbohydrates and peptides, and oxidized charcoal. At pH 5 the sorption
      affinities of tetracycline to SHA and CHA were very close, but remarkably
      stronger than that to functionality-free model polymeric sorbents (polyethylene
      and polystyrene). Meanwhile, despite the much lower hydrophobicity, tetracycline
      displayed stronger sorption to the humic acids than nonpolar, nonionic 1,3,5
      trichlorobezene. It is thus concluded that specific complexation (H--bonding and
      cation exchange) with the humic functionality overwhelmed hydrophobic effect in
      sorption when tetracycline was dominated by the zwitterion. Furthermore,
      modifying solution chemistry conditions (pH, ionic strength of NaCl and CaCl2,
      and the presence of Zn2+) generally caused more prominent effects on tetracycline
      sorption to CHA than to SHA, which was attributed to the higher surface charge of
      CHA. Results of this research demonstrate the importance of the structural nature
      of humic acids in antibiotic sorption.

PMID- 20821651
TI  - A closer look at bioaccumulation of petroleum hydrocarbon mixtures in aquatic
      worms.
AB  - Petroleum hydrocarbons (oils) are ubiquitous in the aquatic environment, and
      adequate risk assessment is thus essential. Bioaccumulation plays a key role in
      risk assessment, but the current knowledge on bioaccumulation of oils is limited.
      Therefore, this process was studied in detail, using the aquatic worm,
      Lumbriculus variegatus, and 14 field-contaminated sediments. The main focus
      during the present study was on uptake kinetics, the relationship between oil
      boiling point fraction and uptake, and effects of sediment characteristics.
      Uptake kinetics became slower with increasing boiling point fraction, but 70 to
      90% of the equilibrium situation was reached within the standard exposure
      duration of 28 d. Worms accumulated sedimentary petroleum hydrocarbons in the
      range of C(10) to C(34), a range much wider than expected. Biota-to-sediment
      accumulation factors (BSAFs) for separate boiling point fractions were constant
      and around the proposed value of 1 to 2 up to C(22), but gradually decreased
      beyond this point. The decrease was probably caused by a combination of
      nonequilibrium conditions and enhanced sorption of higher boiling point fractions
      to sediments; the latter possibly due to the presence of strongly sorbing
      separate oil phases or black carbon. A negative relationship was observed between
      BSAF and oil concentration in sediment, which was explained by the presence of
      separate oil phases at high oil concentrations. These strongly sorbing phases may
      limit their own availability, particularly when being highly weathered; worms may
      also avoid them. The observed phenomena have obvious implications for
      bioaccumulation assessment of oils and suggest that the current risk assessment
      procedure for oils in sediments may lead to erroneous results.

PMID- 20821652
TI  - Steroid determination in fish plasma using capillary electrophoresis.
AB  - A capillary separation method that incorporates pH-mediated stacking is employed
      for the simultaneous determination of circulating steroid hormones in plasma from
      Perca flavescens (yellow perch) collected from natural aquatic environments. The
      method can be applied to separate eight steroid standards: progesterone,
      17alpha,20beta-dihydroxypregn-4-en-3-one, 17alpha-hydroxyprogesterone,
      testosterone, estrone, 11-ketotestosterone, ethynyl estradiol, and 17beta
      estradiol. Based on screening of plasma, the performance of the analytical method
      was determined for 17alpha,20beta-dihydroxypregn-4-en-3-one, testosterone, 11
      ketotestosterone, and 17beta-estradiol. The within-day reproducibility in
      migration time for these four steroids in aqueous samples was < or =2%. Steroid
      quantification was accomplished using a calibration curve obtained with external
      standards. Plasma samples from fish collected from the Choptank and Severn
      Rivers, Maryland, USA, stored for up to one year were extracted with ethyl
      acetate and then further processed with anion exchange and hydrophobic solid
      phase extraction cartridges. The recovery of testosterone and 17beta-estradiol
      from yellow perch plasma was 84 and 85%, respectively. Endogenous levels of
      testosterone ranged from 0.9 to 44 ng/ml, and when detected 17alpha,20beta
      dihydroxypregn-4-en-3-one ranged from 5 to 34 ng/ml. The reported values for
      testosterone correlated well with the immunoassay technique. Endogenous
      concentrations of 17beta-estradiol were < or =1.7 ng/ml. 11-Ketotestosterone was
      not quantified because of a suspected interferant. Higher levels of
      17alpha,20beta-dihydroxypregn-4-en-3-one were found in male and female fish in
      which 17beta-estradiol was not detected. Monitoring multiple steroids can provide
      insight into hormonal fluctuations in fish.

PMID- 20821653
TI  - Perfluorooctane sulfonate toxicity, isomer-specific accumulation, and maternal
      transfer in zebrafish (Danio rerio) and rainbow trout (Oncorhynchus mykiss).
AB  - Perfluorooctane sulfonate (PFOS; C(8)F(17)SO(3) (-)) bioaccumulation and toxicity
      have been demonstrated in both aquatic and terrestrial organisms. The majority of
      investigations have examined total PFOS concentrations in wildlife and in
      toxicity testing, but isomer-specific monitoring studies are less common, and no
      laboratory-based study of PFOS isomer accumulation in fish has been reported. The
      present study examined accumulation and maternal transfer of PFOS isomers in
      zebrafish and tissue-specific accumulation of PFOS isomers in trout parr. A
      median lethal dose (LC50) of 22.2 and 2.5 mg/L was calculated for adult zebrafish
      and trout parr, respectively. A two-week PFOS exposure resulted in tissue
      specific PFOS accumulation in trout, with maximum concentrations identified in
      the liver tissue (>50 microg/g). Prior exposure to PFOS as alevin did not affect
      the accumulation of PFOS in tissues later in life. In both species, accumulation
      of branched PFOS isomers generally occurred to a lesser extent than linear PFOS,
      which may explain the relative deficiency of branched PFOS isomers in some
      aquatic species in the field. Analysis of exposed trout tissues indicated that
      isomer discrimination may occur at the level of elimination or uptake and
      elimination processes in the kidney or gill, respectively. When zebrafish
      underwent a reproductive cycle in the presence of PFOS, approximately 10% (wt) of
      the adult PFOS body burden was transferred to the developing embryos, resulting
      in a higher total PFOS concentration in eggs (116 +/- 13.3 microg/g) than in the
      parent fish (72.1 +/- 7.6 microg/g). The isomer profile in eggs was not
      significantly different from that of adults, suggesting that the maternal
      transfer of branched and linear PFOS isomers in fish is largely nonisomer
      specific.

PMID- 20821654
TI  - Effects of rice straw-derived dissolved organic matter on pyrene sorption by
      soil.
AB  - The objectives of the present study were to elucidate the chemical and structural
      properties of dissolved organic matter (DOM) derived from aerobic decay of rice
      straw and to quantify the effect of the DOM on the sorption of pyrene on soil.
      The DOM samples were obtained from microcosms incubated at 0, 21, 63, and 180 d.
      The bulk DOM samples were fractionated to four fractions: hydrophilic matter
      (HIM), acid-insoluble matter (AIM), hydrophobic acid (HOA), and hydrophobic
      neutral (HON) fractions. The bulk DOM and the four DOM fractions were
      characterized for their elemental compositions and functionalities. The results
      showed that HIM had the highest H/C atomic ratios, whereas HOA and AIM had the
      lowest H/C atomic ratios. These DOM samples were used as the background DOMs in
      the initial aqueous solutions for measuring sorption of pyrene on a paddy soil.
      The results indicated that, among the four DOM fractions, HOA, HON, and AIM
      significantly lowered the pyrene sorption coefficients, but HIM had little or no
      effect on the pyrene sorption by the soil. It appears that less polar AIM and HON
      had stronger binding affinities for pyrene in water, reducing the sorption
      coefficient for the soil, whereas more polar and less aromatic HIM had much
      weaker binding affinity for pyrene in water, causing little or no effect on the
      pyrene sorption by the soil. The present study showed that rice straw-derived DOM
      may enhance desorption and transport of organic pollutants in soil-water systems.

PMID- 20821655
TI  - Influence of black carbon and chemical planarity on bioavailability of sediment
      associated contaminants.
AB  - Black carbon (BC) and chemical properties may play a significant role in defining
      the bioavailability of hydrophobic organic compounds (HOCs) in sediment. In the
      current study, bioavailability of four HOCs with differing planarity was
      determined in sediments amended with two types of BC (soot and charcoal) at
      different concentrations by matrix solid-phase microextraction (matrix-SPME) and
      bioaccumulation testing using the freshwater oligochaete Lumbriculus variegatus.
      Furthermore, the applicability of the matrix-SPME method to bioavailability
      estimation in BC-amended sediment was tested. The charcoal treatment
      significantly reduced the bioaccumulation of the planar compounds (3,3',4,4'
      tetrachlorobiphenyl and benzo[a]pyrene) in L. variegatus, and the matrix-SPME
      method showed a similar trend as contaminant bioaccumulation in L. variegatus.
      Conversely, manipulation of sediment with soot had no effect or slightly
      increased bioavailability of the planar compounds in both bioaccumulation and
      matrix-SPME tests. Little if any affect was noted in bioavailability of the
      nonplanar compounds (2,2',4,4',5,5'-hexachlorobiphenyl and permethrin) with the
      soot and charcoal amendments. Results showed that the role of BC in defining
      bioavailability of HOCs depends not only on the type and concentrations of BC
      present, but also the planarity of the HOCs.

PMID- 20821656
TI  - Toxicity of brominated volatile organics to freshwater biota.
AB  - As part of a larger study investigating the fate and effects of brominated
      volatile organic compounds (VOCs) in contaminated groundwaters discharging to
      surface waters, the toxicity of 1,2 dibromoethene (DBE) and 1,1,2-tribromoethene
      (TriBE) to freshwater aquatic biota was investigated. Their toxicity to bacteria
      (Microtox(R)), microalgae (Chlorella sp.), cladocerans (Ceriodaphnia dubia),
      duckweed (Lemna sp.) and midges (Chironomus tepperi) was determined after careful
      optimization of the test conditions to minimize chemical losses throughout the
      tests. In addition, concentrations of DBE and TriBE were carefully monitored
      throughout the bioassays to ensure accurate calculation of toxicity values. 1,2
      Dibromoethene showed low toxicity to most species, with concentrations to cause
      50% lethality or effect (LC/EC50 values) ranging from 28 to 420 mg/L, 10%
      lethality or effect (LC/EC10 values) ranging from 18 to 94 mg/L and no-observed
      effect concentrations (NOECs) ranging from 22 to 82 mg/L. 1,1,2-Tribromoethene
      was more toxic than DBE, with LC/EC50 values of 2.4 to 18 mg/L, LC/EC10 values of
      0.94 to 11 mg/L and NOECs of 0.29 to 13 mg/L. Using these limited data, together
      with data from the only other published study on TriBE, moderate-reliability
      water quality guidelines (WQGs) were estimated from species sensitivity
      distributions. The proposed guideline trigger values for 95% species protection
      with 50% confidence were 2 mg/L for DBE and 0.03 mg/L for TriBE. The maximum
      concentrations of DBE and TriBE in nearby surface waters (3 and 1 microg /L,
      respectively) were well below these WQGs, so the risk to the freshwater
      environment receiving contaminated groundwater inflows was considered to be low,
      with hazard quotients <1 for both VOCs. Environ.

PMID- 20821657
TI  - Macroinvertebrate responses to insecticide application between sprayed and
      adjacent nonsprayed ditch sections of different sizes.
AB  - Under typical agricultural use of an insecticide, it is likely that only part of
      an edge-of-field drainage ditch will be directly contaminated by spray drift. The
      response, including recovery, of aquatic macroinvertebrates in sprayed ditch
      sections may be affected by immigration of organisms from adjacent nonsprayed
      ditch sections, but also the population dynamics in nonsprayed sections (refuges)
      may be affected by nearby contaminated patches (known as action at a distance).
      Experimental ditches were used to study the influence of the presence of nearby
      refuges on the responses of macroinvertebrates in ditch sections directly sprayed
      with the insecticide lufenuron, and vice versa. The treatment regimes differed in
      the proportion of the ditch (0, 33, 67, and 100% of surface area) that was
      sprayed to reach a lufenuron concentration of 3 microg/L in the water column of
      the sprayed ditch section. In sprayed ditch sections, clear treatment-related
      effects were observed for adult midges in the emergence traps and for aquatic
      arthropods (mainly juveniles) in the artificial substrate/sweep net samples. The
      extent in magnitude and duration of effects in sprayed ditch sections was overall
      larger when a larger proportion of the ditch was sprayed and/or the distance to
      the refuge was larger. In nonsprayed ditch sections of partially treated ditches,
      treatment-related effects were absent or minor for macroinvertebrates that
      predominantly dwell on or in the sediment compartment, particularly at a larger
      distance from the sprayed ditch sections. More mobile arthropods that
      predominantly dwell in the water column showed clear treatment-related effects in
      the nonsprayed ditch sections as well, but action at a distance was smaller if a
      smaller proportion of ditch was treated.

PMID- 20821658
TI  - Cadmium toxicity on the freshwater microalga Chlamydomonas moewusii Gerloff:
      Biosynthesis of thiol compounds.
AB  - Cadmium (Cd) toxicity and production of different thiols (phytochelatins,
      glutathione, gamma-Glu-Cys and cysteine) were studied in the microalga
      Chlamydomonas moewusii exposed to different concentrations of this metal (1, 2,
      4, 6, 8, and 10 mg/L) for 96 h. The inhibitory effect of Cd on growth was
      demonstrated. The value of EC50 (metal concentration which reduces the population
      growth to 50% of the control) obtained for this microalga was estimated at 4.1 +/
      0.8 mg/L of Cd after 96 h of exposure. The amount of thiol compounds synthesized
      by C. moewusii changed with Cd concentration. Cysteine concentrations were
      significantly higher compared to those of gamma-Glu-Cys and glutathione in all
      the Cd concentrations assayed. The amino acid cysteine reached its higher levels
      in those cultures in which a decrease in the concentration of phytochelatins
      (PCs) was observed. Both cysteine and glutathione concentrations showed
      significant differences along the Cd concentrations assayed, while the amount of
      gamma-Glu-Cys detected remained stable. The PCs detected were of two, three, and
      four subunits. The level of PC(2) was higher than that of PC(3) and PC(4). PC(4)
      was detected only in the cultures exposed to the Cd concentrations of 1 and 2
      mg/L, in which the synthesis of phytochelatins was higher. A rapid increase in
      the production of PC(2) and PC(3) was observed up to a Cd concentration of 2
      mg/L, after which their levels began to decrease. Phytochelatins were not
      detected in cultures without Cd (controls) and in those exposed to the maximum Cd
      concentration (10 mg/L), in which cell growth was completely inhibited.

PMID- 20821659
TI  - Roundup and amphibians: the importance of concentration, application time, and
      stratification.
AB  - The widespread use of pesticides raises the possibility that non-target organisms
      might also be affected. To assess this, the traditional approach has been to
      conduct short-term laboratory experiments spanning a range of lethal
      concentrations and some longer-duration experiments at sublethal concentrations.
      While this approach has been very useful, less attention has been paid to the
      timing of exposure and the impacts of multiple, small exposures versus single,
      large exposures. We examined the role of application amount, timing, and
      frequency using outdoor mesocosm communities containing larval amphibians (Rana
      sylvatica and Bufo americanus) and using a commercial formulation of the
      herbicide glyphosate (Roundup Original MAX(R)). Consistent with past studies,
      exposures of up to 3 mg acid equivalent (a.e.)/L caused substantial amphibian
      death. However, the amount of death was considerably higher when the herbicide
      was applied earlier in the experiment than later in the experiment. Single, large
      applications (at different times) had larger effects on tadpole mortality and
      growth than multiple, small applications (of the same total amount). The results
      may reflect an acclimation to the herbicide over time. In treatments with high
      tadpole mortality, there was no resulting increase in periphyton, suggesting that
      the reduction in tadpole herbivory might have been offset by direct negative
      impacts of the herbicide. We also discovered that temperature stratification
      caused herbicide stratification, with higher concentrations near the surface.
      Such stratification has important implications to the habitat choices of
      ectotherms that might prefer surface waters for thermoregulation or prefer deeper
      waters to avoid predators. Collectively, the present study demonstrates the
      importance of examining multiple applications times and frequencies to understand
      the impacts of pesticides on organisms.

PMID- 20821660
TI  - Comparison of metal concentrations in Corbicula fluminea and Elliptio
      hopetonensis in the Altamaha River system, Georgia, USA.
AB  - The present study evaluated the use of the invasive clam Corbicula fluminea as a
      surrogate for metal accumulation in native mussels. The tissue concentrations of
      As, Cd, Cu, Hg, Mn, Ni, Pb, and Zn were analyzed in Corbicula and a native
      Unionid mussel species (Elliptio hopetonensis) collected from 13 sites in the
      Altamaha River system (GA, USA). Corbicula accumulated greater concentrations of
      As, Cd, Cu, Hg, and Ni when compared to E. hopetonensis at the same sites. The
      reverse was true for the metals Mn and Zn, with E. hopetonensis accumulating
      greater concentrations than Corbicula. Concentrations of As, Cd, Cu, Hg, and Pb
      were found to be significantly (alpha = 0.05) positively correlated between the
      two species. Greater water alkalinity and hardness tended to negatively correlate
      with metal accumulation, while organism size tended to correlate positively with
      tissue concentrations. Tissue Cd, Cu, and Pb concentrations demonstrated a
      correlation between bivalve tissues and concentrations of those metals in fine
      sediments. These correlations were significant (alpha = 0.05) for Cd and Cu
      concentrations in Corbicula and Pb concentrations in E. hopetonensis. The present
      findings support the hypothesis that bioaccumulation of some metals by Corbicula
      can be used to approximate levels accumulated by co-occurring native mussel
      species.

PMID- 20821661
TI  - Hepatic gene expression in rainbow trout (Oncorhynchus mykiss) exposed to
      different hydrocarbon mixtures.
AB  - Traditional biomarkers for hydrocarbon exposure are not induced by all petroleum
      substances. The objective of this study was to determine if exposure to a crude
      oil and different refined oils would generate a common hydrocarbon-specific
      response in gene expression profiles that could be used as generic biomarkers of
      hydrocarbon exposure. Juvenile rainbow trout (Oncorhynchus mykiss) were exposed
      to the water accommodated fraction (WAF) of either kerosene, gas oil, heavy fuel
      oil, or crude oil for 96 h. Tissue was collected for RNA extraction and
      microarray analysis. Exposure to each WAF resulted in a different list of
      differentially regulated genes, with few genes in common across treatments.
      Exposure to crude oil WAF changed the expression of genes including cytochrome
      P4501A (CYP1A) and glutathione-S-transferase (GST) with known roles in
      detoxification pathways. These gene expression profiles were compared to others
      from previous experiments that used a diverse suite of toxicants. Clustering
      algorithms successfully identified gene expression profiles resulting from
      hydrocarbon exposure. These preliminary analyses highlight the difficulties of
      using single genes as diagnostic of petroleum hydrocarbon exposures. Further work
      is needed to determine if multivariate transcriptomic-based biomarkers may be a
      more effective tool than single gene studies for exposure monitoring of different
      oils.

PMID- 20821662
TI  - Toxicity of short-term copper exposure to early life stages of red sea bream,
      Pagrus major.
AB  - Acute (0, 0.1, 0.2, 0.4, 0.8, 1.6 mg Cu/L) and chronic (0, 0.02, 0.04, 0.06,
      0.08, 0.10, 0.12 mg Cu/L) toxicity tests of Cu with embryonic and larval red sea
      bream, Pagrus major, were carried out to investigate their biological responses
      to Cu exposure in static water at 18 +/- 1 degrees C (dissolved organic carbon,
      1.8 +/- 0.65 mg C/L; hardness, 6,183 +/- 360 mg CaCO3/L; salinity, 33 +/- 1 per
      thousand). The 24- and 48-h LC50 (median lethal concentration) values of Cu for
      embryos were 0.23 and 0.15 mg/L, whereas the 48-, 72-, and 96-h LC50 values for
      larvae were 0.52, 0.19, and 0.13 mg/L, respectively, suggesting that embryos were
      more sensitive to Cu toxicity than larvae. Copper exposures at > or =0.06 mg
      concentrations caused low hatching success, a delay in the time to hatching of
      embryos, and reductions in the growth and yolk absorption of the larvae, whereas
      high mortality and morphological malformations occurred in the embryos and larvae
      at > or =0.08 mg/L concentrations. Copper concentration did not significantly
      affect the heart rate of the embryos, but it significantly decreased the heart
      rate of the newly hatched larvae when the Cu concentration was > or =0.08 mg/L,
      suggesting that Cu at high concentrations could induce heartbeat disturbances in
      red sea bream more easily at the larval stage than at the embryonic stage.
      Hatching success, time to hatching, growth rate, morphological abnormality, yolk
      absorption, and heart rate were Cu concentration-dependent and could be effective
      endpoints for evaluating Cu toxicity to the early life stages of red sea bream in
      nature.

PMID- 20821663
TI  - Sensitivity of early life stages of freshwater mussels (Unionidae) to acute and
      chronic toxicity of lead, cadmium, and zinc in water.
AB  - Toxicity of lead, cadmium, or zinc to early life stages of freshwater mussels
      (fatmucket, Lampsilis siliquoidea; Neosho mucket, L. rafinesqueana) was evaluated
      in 48-h exposures with mussel larvae (glochidia), in 96-h exposures with newly
      transformed (5-d-old) and two- or six-month-old juvenile mussels, or in 28-d
      exposures with two- or four-month-old mussels in reconstituted soft water. The 24
      h median effect concentrations (EC50s) for fatmucket glochidia (>299 microg Pb/L,
      >227 microg Cd/L, 2,685 microg Zn/L) and 96-h EC50s for two- or six-month-old
      fatmucket (>426 microg Pb/L, 199 microg Cd/L, 1,700 microg Zn/L) were much higher
      than 96-h EC50s for newly transformed fatmucket (142 and 298 microg Pb/L, 16
      microg Cd/L, 151 and 175 microg Zn/L) and Neosho mucket (188 microg Pb/L, 20
      microg Cd/L, 145 microg Zn/L). Chronic values for fatmucket were 10 microg Pb/L,
      6.0 microg Cd/L, and 63 and 68 microg Zn/L. When mussel data from the present
      study and the literature were included in updated databases for deriving U.S.
      Environmental Protection Agency water quality criteria, mussel genus mean acute
      values were in the lower percentiles of the sensitivity distribution of all
      freshwater species for Pb (the 26th percentile), Cd (the 15th to 29th
      percentile), or Zn (the 12th to 21st percentile). The mussel (Lampsilis) genus
      mean chronic value was the lowest value ever reported for Pb (the 9th percentile)
      but was near the middle of the sensitivity distribution for Cd (the 61st
      percentile) or Zn (the 44th percentile). These results indicate that mussels were
      relatively sensitive to the acute toxicity of these three metals and to the
      chronic toxicity of Pb, but were moderately sensitive to the chronic toxicity of
      Cd or Zn compared to other freshwater species.

PMID- 20821664
TI  - Differences in sensitivity but not selectivity of xenoestrogen binding to
      alligator versus human estrogen receptor alpha.
AB  - Reproductive abnormalities in alligators exposed to contaminants in Lake Apopka,
      Florida, USA represent a clear example of endocrine disruption in wildlife.
      Several of these contaminants that are not able to bind to mammalian estrogen
      receptors (such as atrazine and cyanazine) have previously been reported to bind
      to the alligator estrogen receptor from oviductal tissue. Binding of known Lake
      Apopka contaminants to full length estrogen receptors alpha from human (hERalpha)
      and alligator (aERalpha) was assessed in a side-by-side comparison within the
      same assay system. Baculovirus-expressed recombinant hERalpha and aERalpha were
      used in a competitive binding assay. Atrazine and cyanazine were not able to bind
      to either receptor. p,p'-Dicofol was able to bind to aERalpha with a
      concentration inhibiting 50% of binding (IC50) of 4 microM, while only partially
      displacing 17beta-estradiol (E2) from hERalpha and yielding a projected IC50 of
      45 microM. Chemicals that only partially displaced E2 from either receptor,
      including some dichlorodiphenyltrichloroethane (DDT) metabolites and trans
      nonachlor, appeared to have higher affinity for aERalpha than hERalpha. p,p'
      Dicofol-mediated transcriptional activation through aERalpha and hERalpha was
      assessed to further explore the preferential binding of p,p'-dicofol to aERalpha
      over hERalpha. p,p'-Dicofol was able to stimulate transcriptional activation in a
      similar manner with both receptors. However, the in vitro results obtained with
      p,p'-dicofol were not reflected in an in vivo mammalian model, where Kelthane
      (mixed o,p'- and p,p'-dicofol isomers) did not elicit estrogenic effects. In
      conclusion, although there was no evidence of exclusively species-specific
      estrogen receptor binders, some xenoestrogens, especially p,p'-dicofol, had a
      higher affinity for aERalpha than for hERalpha.

PMID- 20821665
TI  - Rhizotoxic effects of silver in cowpea seedlings.
AB  - Silver (Ag) is highly toxic to aquatic organisms, including algae, invertebrate
      animals, and fish, but little information exists on Ag rhizotoxicity in higher
      plants. In two solution culture experiments with approximately 1,000 microM
      Ca(NO3)2 and 5 microM H3BO3 (pH 5.4), 20 to 80% of added Ag (< or =2 microM) was
      lost from solution within approximately 30 min, with a further decrease after 48
      h root growth. Using measured Ag concentrations at the start of the experiments,
      the median effective concentration (EC50) for root elongation rate of cowpea
      (Vigna unguiculata [L.] Walp. cv. Caloona) was 0.010 microM Ag in the first 4 h
      of exposure (0.021 microM in the first 8 h). This demonstrates that Ag (as Ag+)
      is rapidly rhizotoxic to cowpea seedlings at concentrations similar to those that
      are toxic to freshwater biota. Rupturing of rhizodermal and outer cortical layers
      was evident after 48 h with 0.13 to 0.57 microM Ag initially in solution, being
      most severe at 0.13 or 0.25 microM Ag. An additional experiment showed that
      ruptures were first evident after 20 h exposure to 0.17 microM Ag, with increased
      severity of rupturing over time. The rhizotoxic effects of Ag are similar to
      those of some other trace metals (e.g., Cu, Al, La) that bind strongly to hard
      ligands and weakly to soft ligands. The similarity of rupturing effects, despite
      the difference in strong binding to soft ligands by Ag and to hard ligands by the
      other metals, suggests a distinctive metabolic effect of Ag that binds only
      weakly to hard ligands.

PMID- 20821666
TI  - Exposure of three generations of the estuarine sheepshead minnow (Cyprinodon
      variegatus) to the androgen, 17beta-trenbolone: effects on survival, development,
      and reproduction.
AB  - Estimating long-term effects of endocrine-disrupting chemicals on a species is
      important to assessing the overall risk to the populations. The present study
      reports the results of a 42-week exposure of estuarine sheepshead minnows
      (Cyprinodon variegatus) to the androgen, 17beta-trenbolone (Tb) conducted to
      determine if partial-(F0) or single-generation (F1) fish exposures identify
      multigenerational (F0-F3) effects of androgens on fish. Adult F0 fish were
      exposed to 0.007, 0.027, 0.13, 0.87,and 4.1 microg Tb/L, the F1 generation to <
      or =0.87 microg Tb/L, the F2 fish to < or =0.13 microg Tb/L, and the F3 fish to <
      or =0.027 microg Tb/L. The highest concentrations with reproducing populations at
      the end of the F0, F1, and F2 generations were 4.1, 0.87, and 0.027 microg Tb/L,
      respectively. Reproduction in the F0, F1, and F2 generations was significantly
      reduced at 0.87, 0.027, and 0.027 microg Tb/L, respectively. Fish were
      significantly masculinized in the F1 generation exposed to 0.13 microg Tb/L or
      greater. Female plasma vitellogenin was significantly reduced in F0 fish exposed
      to > or =0.87 microg Tb/L. Gonadosomatic indices of the F0 and F1 generations
      were significantly increased at 0.87 and 0.13 microg Tb/L in the F0 and F1
      generation, respectively, and were accompanied by ovarian histological changes.
      Reproduction was the most consistently sensitive measure of androgen effects and,
      after a life-cycle exposure, the daily reproductive rate predicted concentrations
      affecting successive generations. The present study provides evidence that a
      multiple generation exposure of fish to some endocrine-disrupting chemicals can
      result in developmental and reproductive changes that have a much greater impact
      on the success of a species than was indicated from shorter term exposures.

PMID- 20821667
TI  - 2,3,4,7,8-pentachlorodibenzofuran is a more potent cytochrome P4501A inducer than
      2,3,7,8-tetrachlorodibenzo-p-dioxin in herring gull hepatocyte cultures.
AB  - Concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD),
      2,3,4,7,8-pentachlorodibenzofuran (PeCDF), and 2,3,7,8-tetrachlorodibenzofuran
      (TCDF) on cytochrome P4501A (CYP1A) induction were determined in primary cultures
      of embryonic herring gull (Larus argentatus) hepatocytes exposed for 24 h. Based
      on the concentration that induced 50% of the maximal response (EC50), the
      relative potencies of TCDD and TCDF did not differ by more than 3.5-fold.
      However, also based on the EC50, PeCDF was 40-fold, 21-fold, and 9.8-fold more
      potent for inducing ethoxyresorufin-O-deethylase (EROD) activity, CYP1A4 mRNA
      expression, and CYP1A5 mRNA expression than TCDD, respectively. The relative
      CYP1A-inducing potencies of PeCDF and of other dioxin-like chemicals (DLCs) in
      herring gull hepatocytes (HEH RePs), along with data on concentrations of DLCs in
      Great Lakes herring gull eggs, were used to calculate World Health Organization
      toxic equivalent (WHO-TEQ) concentrations and herring gull embryonic hepatocyte
      toxic equivalent (HEH-TEQ) concentrations. The analysis indicated that, when
      using avian toxic equivalency factors (TEFs) recommended by the WHO, the relative
      contribution of TCDD (1.1-10.2%) to total WHO-TEQ concentration was higher than
      that of PeCDF (1.7-2.9%). These results differ from the relative contribution of
      TCDD and PeCDF when HEH RePs were used; PeCDF was a major contributor (36.5
      52.9%) to total HEH-TEQ concentrations, whereas the contribution by TCDD (1.2
      10.3%) was less than that of PeCDF. The WHO TEFs for avian species were largely
      derived from studies with the domestic chicken (Gallus gallus domesticus). The
      findings of the present study suggest that it is necessary to determine the
      relative potencies of DLCs in wild birds and to re-evaluate their relative
      contributions to the biochemical and toxic effects previously reported in herring
      gulls and other avian species.

PMID- 20821668
TI  - Relationship between biotic ligand model-based water quality criteria and
      avoidance and olfactory responses to copper by fish.
AB  - The U.S. Environmental Protection Agency's (U.S. EPA) water quality criteria for
      Cu were tested to determine whether they protect fish against neurophysiological
      impairment. From published studies with rainbow trout (Oncorhynchus mykiss),
      Chinook salmon (Oncorhynchus tshawytscha), coho salmon (Oncorhynchus kisutch),
      and fathead minnows (Pimephales promelas), 20% inhibition concentrations (IC20s)
      were calculated for avoidance of Cu-containing water and for impairment of
      electroencephalogram (EEG) and electro-olfactogram (EOG) responses to natural
      odorants in Cu-containing water. Additionally, a Cu-olfactory biotic ligand model
      (BLM) that fits the coho salmon EOG data was parameterized by changing the
      sensitivity parameter in the ionoregulatory-based BLM. The IC20s calculated from
      reported Cu avoidance, EEG, and EOG data and IC20s predicted by the olfactory BLM
      were compared with acute and chronic Cu criteria calculated using U.S. EPA's BLM
      2007 or hardness-adjustment equations. The BLM-based chronic criteria were
      protective in all 16 exposure water-species combinations used in avoidance and
      olfaction experiments. Additionally, the BLM-based acute criteria were protective
      in all 11 exposure water-species combinations in which comparisons could be made
      with olfactory BLM-predicted IC20s but not in two of the 16 exposure water
      species combinations in which comparisons could be made with the reported IC20s
      (which were < or =8% lower than but did not differ significantly from the BLM
      based acute criteria; p > 0.05). In effect, the olfactory BLM factored out the
      relatively high variability in the reported IC20s. It is concluded that the U.S.
      EPA's BLM-based water quality criteria for Cu protect against these types of
      neurophysiological impairment in the six species-endpoint combinations analyzed
      in this paper. However, the U.S. EPA's hardness-based criteria for Cu sometimes
      were considerably underprotective and sometimes were much less protective than
      the BLM-based criteria.

PMID- 20821669
TI  - Comparative toxicity and bioconcentration of nonylphenol in freshwater organisms.
AB  - Degradation of alkylphenol ethoxylates to more persistent alkylphenols such as
      nonylphenol occurs in wastewater treatment plants where nonylphenol is released
      to aquatic systems. In this study, acute and chronic tests were conducted to
      determine the toxicity and bioconcentration of nonylphenol to freshwater
      organisms for use in deriving national water quality criteria. Acute median
      effect concentrations (EC50s) based on loss of equilibrium, immobility, and
      lethality for species representing several taxonomic groups ranged from 21 to 596
      microg/L. The EC50s were up to a factor of 2 less than median lethal
      concentrations (LC50s) and decreased with time over the test periods of 24 to 96
      h. In chronic tests, early life stages of rainbow trout were 14 times more
      sensitive to nonylphenol than in acute tests and approximately 20 times more
      sensitive than Daphnia magna exposed over their complete life cycle. Comparisons
      of chronic test endpoints showed that 20% effect concentrations (EC20s),
      determined by regression testing, and chronic values, determined by hypothesis
      testing, were similar for both the rainbow trout and Daphnia magna. The lowest
      mean tissue-effect concentrations of nonylphenol appeared to be greater for the
      fathead minnow than bluegill, and ranged from approximately 130 to 160 microg/g
      after 96-h exposure and from approximately 20 to 90 microg/g after 28-d exposure.
      Mean lipid normalized bioconcentration factors (BCFs) associated with no-effect
      concentrations were approximately 180 and 50 for the fathead minnow and bluegill,
      respectively. The present test results suggest that long-term exposures to
      nonylphenol at concentrations found in some surface waters could adversely impact
      sensitive components of freshwater communities.

PMID- 20821670
TI  - An evaluation of the influence of substrate on the response of juvenile
      freshwater mussels (fatmucket, Lampsilis siliquoidea) in acute water exposures to
      ammonia.
AB  - Acute 96-h ammonia toxicity to three-month-old juvenile mussels (Lampsilis
      siliquoidea) was evaluated in four treatments (water-only, water-only with
      feeding, water and soil, and water and sand) using an exposure unit designed to
      maintain consistent pH and ammonia concentrations in overlying water and in pore
      water surrounding the substrates. Median effect concentrations (EC50s) for total
      ammonia nitrogen in the four treatments ranged from 5.6 to 7.7 mg/L and median
      lethal concentrations (LC50s) ranged from 7.0 to 11 mg/L at a mean pH of 8.4.
      Similar EC50s or LC50s with overlapping 95% confidence intervals among treatments
      indicated no influence of substrate on the response of mussels in acute exposures
      to ammonia.

PMID- 20821671
TI  - Disturbance of perfluorooctanoic acid on development and behavior in Drosophila
      larvae.
AB  - Perfluorooctanoic acid (PFOA) is a well-known perfluorinated compound (PFC), and
      its toxicological impact is currently of worldwide concern. In this study, we
      sought to evaluate the potential biological effects and modes of action of PFOA
      in a range of physiologically and developmentally related phenotypes in the fruit
      fly Drosophila melanogaster. The results clearly indicated that the toxic effects
      of PFOA at the organismal level were associated with the developmental status of
      the organism, with larvae being most sensitive to this chemical. Except for the
      decreased weight of both sexes and the reduced longevity of male adults, PFOA had
      a robust effect on larval development, as determined by reduced body volume,
      aberrant foraging behavior, molting arrest, and polyphasic lethality. Remarkably,
      nutrient supplementation of the diet efficiently rescued the lethal effect of
      high PFOA concentrations on larval development. This result indicated that PFOA
      probably competed with nutritional components, leading to a disruption of the
      metabolic pathways responsible for larval development.

PMID- 20821672
TI  - A similarity-index-based method to estimate chemical concentration limits
      protective for ecological communities.
AB  - A new method is presented to determine retrospectively proportional changes of
      species composition in a community at risk from particular concentrations of
      chemical stressors. The method makes estimates with some similarities to those
      claimed by species sensitivity distributions (SSDs) but is based on species
      presence/absence field data and requires assumptions that are more likely to be
      met. The method uses Jaccard's index (JI), the proportion of species in common to
      two samples. At a similar level of contamination, the occurrence of species is
      usually highly variable, and thus JI values between individual pairs of samples
      can be low. However, by pooling samples with a similar contamination level, an
      increasingly complete set of species present at this level of contamination is
      gained. Our method involves calculating JI between randomly selected groups of
      samples (pooled sample sets) with similar and different levels of contamination.
      It then relates changes in JI to the difference in contamination and produces
      estimates of the proportional change in species between preselected categories of
      contamination. The application of the method is illustrated by using data on
      riverine freshwater macroinvertebrates exposed to salinity in southeastern
      Australia; pesticide runoff potential in the Aller River Catchment, Germany; and
      metal pollution (principle Cu) in the Clark Fork River Catchment, Montana, USA.

PMID- 20821674
TI  - Multicriteria decision analysis to assess options for managing contaminated
      sediments: Application to Southern Busan Harbor, South Korea.
AB  - Many years of untreated effluent discharge from residential areas, a shipyard, a
      marina, and a large fish market resulted in substantial contamination of bottom
      sediment in Southern Busan Harbor, South Korea. Contaminants in these sediments
      include heavy metals and organic compounds. Newly introduced regulations for
      ocean disposal of dredged material in South Korea pose significant challenges,
      because the previous practice of offshore disposal of contaminated dredged
      material was no longer possible after August 2008. The South Korean government
      has mandated that such sediments be assessed in a way that identifies the most
      appropriate dredged material management alternative, addressing environmental,
      social, and cost objectives. An approach using multicriteria decision analysis
      (MCDA) in combination with comparative risk assessment was used as a systematic
      and transparent framework for prioritizing several dredged sediment management
      alternatives. We illustrate how MCDA can recognize the multiple goals of
      contaminated sediment management. Values used in weighting decision criteria were
      derived from surveys of stakeholders who were sediment management professionals,
      business owners, or government decision makers. The results of the analysis
      showed that land reclamation was the preferred alternative among cement-lock,
      sediment washing, 3 contained aquatic disposal alternatives (one in combination
      with a hopper dredge), geotextile tubes, solidification, and land reclamation
      after solidification treatment. Land reclamation was the preferred alternative,
      which performed well across all MCDA objectives, because of the availability of a
      near-shore confined disposal facility within a reasonable distance from the
      dredging area.

PMID- 20821675
TI  - A decision-analysis approach for contaminated dredged material management in
      South Korea.
AB  - To meet London Protocol requirements, South Korea is preparing to reduce the need
      for disposal of dredged material at sea. The new requirements controlling ocean
      disposal of dredged material pose significant challenges to the South Korean
      government, because the previous practice of offshore disposal of contaminated
      dredged material is no longer permitted. Hence, other alternatives for treating
      and disposing of contaminated dredged material are being evaluated and selected
      for implementation. A new management and decision approach is therefore needed
      for regulators and implementers to show what information and what decision-making
      processes were used to make the decision, to increase administrative transparency
      for such projects in the public domain. To address this need, an iterative
      approach was developed for dredged material management that includes the
      essential elements of process, people, and tools needed for successful
      environmental decision making. The approach has 6 steps: problem definition,
      developing objectives and criteria, identifying alternatives, performing the
      evaluation, comparing alternatives, and selecting the preferred alternative. The
      primary objective of the approach is to provide a systematic means of exploring
      contaminated dredged material management alternatives in South Korea using
      criteria that integrate risk with economic and stakeholder value information. The
      approach incorporates the desired decision-making attributes of transparency,
      comparative analysis, and inclusion of public input. Although it was developed
      for South Korea, the approach can be applied in any situation in which dredged
      material management alternatives are being considered to manage contaminated
      sediment risks.

PMID- 20821676
TI  - Refined avian risk assessment for aldicarb in the United States.
AB  - Aldicarb was recently reviewed by the US Environmental Protection Agency (USEPA)
      for re-registration eligibility. In this paper, we describe a refined avian risk
      assessment for aldicarb that was conducted to build upon the screening-level
      methods used by USEPA. The goal of the refined ERA was to characterize and
      understand better the risks posed by aldicarb to birds in areas where the
      pesticide is applied. Aldicarb is a systemic insecticide sold in granular form
      under the trade name Temik. It is applied directly to soil and is used to control
      mites, nematodes, and aphids on a variety of crops (e.g., cotton, potatoes,
      peanuts). Consumption of grit is necessary for proper digestion in many bird
      species, particularly for granivores and insectivores. Thus, aldicarb granules
      may be mistaken for grit by birds. The Granular Pesticide Avian Risk Assessment
      Model (GranPARAM) is described in a companion paper and was used to estimate the
      probability and magnitude of effects to flocks of birds that frequent aldicarb
      treated fields. One hundred thirty-five exposure scenarios were modeled that
      together include a range of bird species, crops, application methods and rates,
      and regions in the United States. The results indicated that, even for the most
      sensitive bird species, the risks associated with the agricultural use of
      granular aldicarb are negligible to low. There are several reasons for the
      limited risk: 1) the Temik formulation includes a gypsum core and a graphite
      coating and is black in color, all of which have been shown to be unattractive to
      birds, and 2) the pesticide is applied subsurface and rapidly dissolves following
      contact with water. The fact that no bird kill incidents involving appropriate
      label uses of aldicarb have been conclusively documented in the United States
      over its 38 years of use supports the results of this refined risk assessment.

PMID- 20821677
TI  - Refined aquatic risk assessment for aldicarb in the United States.
AB  - Aldicarb is a systemic insecticide applied directly to soil and to control mites,
      nematodes, and aphids on a variety of crops (e.g., cotton, potatoes, peanuts). It
      is highly soluble in water (6,000 mg/L) and mobile in soils (K(oc) = 100). As a
      result, aldicarb has the potential to be transported to aquatic systems close to
      treated fields. The US Environmental Protection Agency (USEPA) recently conducted
      an aquatic screening-level ERA for aldicarb as part of the re-registration review
      process. We conducted a refined risk assessment for aldicarb to characterize
      better the risks posed by aldicarb to fish and invertebrates inhabiting small
      freshwater ponds near agricultural areas. For the exposure assessment, tier II
      PRZM/EXAMS (Predicted Root Zone Model [PRZM] and Exposure Analysis Modelling
      System [EXAMS]) modelling was conducted to estimate 30-y distributions of peak
      concentrations of aldicarb and the carbamate metabolites (aldicarb sulfoxide,
      aldicarb sulfone) in surface waters of a standard pond arising from different
      uses of aldicarb. The effects assessment was performed using a species
      sensitivity distribution (SSD) approach. The resulting risk curves as well as
      available incident reports suggest that risks to freshwater fish and
      invertebrates from exposure to aldicarb are minor. The available monitoring data
      did not provide conclusive evidence about risks to aquatic biota.

PMID- 20821678
TI  - Release of active pharmaceutical ingredients from manufacturing sites--need for
      new management strategies.

PMID- 20821680
TI  - Illicit drugs in the environment: Emerging contaminants and indicators of drug
      abuse.

PMID- 20821681
TI  - Improving aquatic ecological assessments.

PMID- 20821682
TI  - Sperm toxicity and the reproductive ecology of marine invertebrates.

PMID- 20821683
TI  - Irreversible climate change will also change environmental assessment and
      management.

PMID- 20821684
TI  - Integrating population modeling into ecological risk assessment.

PMID- 20821685
TI  - Global climate change and environmental contaminants: a SETAC call for research.

PMID- 20821686
TI  - Calibrating biomonitors to ecological disturbance: a new technique for explaining
      metal effects in natural waters.
AB  - Bioaccumulated toxic metals in tolerant biomonitors are indicators of metal
      bioavailability and can be calibrated against metal-specific responses in
      sensitive species, thus creating a tool for defining dose-response for metals in
      a field setting. Dose-response curves that define metal toxicity in natural
      waters are rare. Demonstrating cause and effect under field conditions and
      integrated chemical measures of metal bioavailability from food and water is
      problematic. The total bioaccumulated metal concentration in any organism that is
      a net accumulator of the metal is informative about metal bioavailability summed
      across exposure routes. However, there is typically no one universal metal
      concentration that is indicative of toxicity, especially across species, largely
      because of interspecies differences in detoxification. Stressed organisms are
      also only present across a narrow range in the dose-response curve, limiting the
      use of singles species as both biomonitors and bioindicator of stress. Herein we
      show, in 3 field settings, that bioaccumulated Cu concentrations in a metal
      tolerant, riverine biomonitor (species of the caddisfly genus Hydropsyche spp.)
      can be calibrated against metal-specific ecological responses across very wide
      ranges of contamination. Using the calibrated dose-response, we show that reduced
      abundance of species and individuals from particularly sensitive mayfly families
      (heptageniid mayflies) is more than 2-fold more sensitive to bioavailable Cu than
      other traditional measures of stress like EPT or total number of benthic
      macroinvertebrate species. We propose that this field dose-response curve be
      tested more widely for general application, and that calibrations against other
      stress responses be developed for biomonitors from lakes, estuaries, and coastal
      marine ecosystems.

PMID- 20821687
TI  - Efficiency of sediment quality guidelines for predicting toxicity: the case of
      the St. Lawrence River.
AB  - Multitiered frameworks that are designed for risk assessment of contaminated
      sediment rely on sediment quality guidelines (SQGs) at the first tier or
      screening level. In the case of contamination by multiple pollutants, results can
      be aggregated under indices such as the mean quotient. A decision is then reached
      (e.g., to dispose of dredged materials in open water) without further
      investigation, provided that the SQGs or the specific values of indices or
      quotients derived from the SQGs are not exceeded. In this way, SQGs and quotients
      play a critical role in environmental protection. As part of the development of a
      tiered framework to assess the environmental risk of materials dredged from the
      St. Lawrence River, we evaluated various quotients based on SQGs available for
      this river with a data set that matches chemistry and toxicity test endpoints.
      The overall efficiency of all tested quotients was rather low, and we then
      examined factors such as sediment grain size, nutrients, metal-binding phases
      (e.g., Al, Fe), and dissolved organic carbon to explain misclassified samples.
      This examination led to the design of a modified tier 1 framework in which SQGs
      are used in combination with decision rules based on certain explanatory factors.

PMID- 20821688
TI  - Probabilistic risk-assessment model for birds exposed to granular pesticides.
AB  - For granular formulations of pesticides, direct consumption by birds is generally
      the most important route of exposure. A probabilistic exposure model was
      developed that estimates how many pesticide granules a bird ingests and, from
      that, the quantity of pesticide ingested. This model, referred to as the
      "granular pesticide avian risk assessment model" (GranPARAM), has input variables
      not included in current screening-level assessments for granular pesticides, such
      as proportion of time for which birds forage in the field, grit ingestion rates,
      attractiveness of pesticide granules compared with natural grit, and proportions
      of soil particles and pesticide granules in the size range consumed by birds. For
      input variables that are uncertain, variable, or both, distributions are used
      rather than point estimates. Monte Carlo analysis is then performed to propagate
      input variable uncertainties through the exposure model for granular pesticides.
      The outputs from the exposure portion of GranPARAM are estimated pesticide doses
      for each of 20 birds of a selected species on each of 1000 fields. The dose for
      each bird is compared with a randomly chosen dose from the dose-response curve
      for that species or an appropriate surrogate. If the exposure dose for a bird
      exceeds the randomly chosen effects dose, the bird is considered dead; otherwise,
      the bird is assumed to be alive. Thus, the risk output from GranPARAM is a bar
      chart showing the percentages of fields with 0/20 dead birds, 1/20 dead birds,
      2/20 dead birds, and so forth.

PMID- 20821690
TI  - Broadening our view on chemical diversity in the Baltic Sea.

PMID- 20821691
TI  - Predicting hormesis in mixtures.

PMID- 20821692
TI  - The nano cocktail: ecotoxicological effects of engineered nanoparticles in
      chemical mixtures.

PMID- 20821693
TI  - Is there a distinct tropical ecotoxicology?

PMID- 20821694
TI  - Epigenetics: an emerging field in environmental toxicology.

PMID- 20821695
TI  - Cradle to cradle: old wine or new spirits?

PMID- 20821696
TI  - Chemical risk assessment: pressures, perceptions and expectations.

PMID- 20821697
TI  - Potential application of ecological models in the European environmental risk
      assessment of chemicals. I. Review of protection goals in EU directives and
      regulations.
AB  - Several European directives and regulations address the environmental risk
      assessment of chemicals. We used the protection of freshwater ecosystems against
      plant protection products, biocidal products, human and veterinary
      pharmaceuticals, and other chemicals and priority substances under the Water
      Framework Directive as examples to explore the potential of ecological effect
      models for a refined risk assessment. Our analysis of the directives,
      regulations, and related guidance documents lead us to distinguish the following
      5 areas for the application of ecological models in chemical risk assessment: 1)
      Extrapolation of organism-level effects to the population level: The protection
      goals are formulated in general terms, e.g., avoiding "unacceptable effects" or
      "adverse impact" on the environment or the "viability of exposed species." In
      contrast, most of the standard ecotoxicological tests provide data only on
      organism-level endpoints and are thus not directly linked to the protection goals
      which focus on populations and communities. 2) Extrapolation of effects between
      different exposure profiles: Especially for plant protection products, exposure
      profiles can be very variable and impossible to cover in toxicological tests. 3)
      Extrapolation of recovery processes: As a consequence of the often short-term
      exposures to plant protection products, the risk assessment is based on the
      community recovery principle. On the other hand, assessments under the other
      directives assume a more or less constant exposure and are based on the ecosystem
      threshold principle. 4) Analysis and prediction of indirect effects: Because
      effects on 1 or a few taxa might have consequences on other taxa that are not
      directly affected by the chemical, such indirect effects on communities have to
      be considered. 5) Prediction of bioaccumulation within food chains: All
      directives take the possibility of bioaccumulation, and thus secondary poisoning
      within the food chain, into account.

PMID- 20821698
TI  - Potential application of population models in the European ecological risk
      assessment of chemicals. II. Review of models and their potential to address
      environmental protection aims.
AB  - Whereas current chemical risk assessment (RA) schemes within the European Union
      (EU) focus mainly on toxicity and bioaccumulation of chemicals in individual
      organisms, most protection goals aim at preserving populations of nontarget
      organisms rather than individuals. Ecological models are tools rarely recommended
      in official technical documents on RA of chemicals, but are widely used by
      researchers to assess risks to populations, communities and ecosystems. Their
      great advantage is the relatively straightforward integration of the sensitivity
      of species to chemicals, the mode of action and fate in the environment of
      toxicants, life-history traits of the species of concern, and landscape features.
      To promote the usage of ecological models in regulatory risk assessment, this
      study tries to establish whether existing, published ecological modeling studies
      have addressed or have the potential to address the protection aims and
      requirements of the chemical directives of the EU. We reviewed 148 publications,
      and evaluated and analyzed them in a database according to defined criteria.
      Published models were also classified in terms of 5 areas where their application
      would be most useful for chemical RA. All potential application areas are well
      represented in the published literature. Most models were developed to estimate
      population-level responses on the basis of individual effects, followed by
      recovery process assessment, both in individuals and at the level of
      metapopulations. We provide case studies for each of the proposed areas of
      ecological model application. The lack of clarity about protection goals in
      legislative documents made it impossible to establish a direct link between
      modeling studies and protection goals. Because most of the models reviewed here
      were not developed for regulatory risk assessment, there is great potential and a
      variety of ecological models in the published literature.

PMID- 20821699
TI  - Summing nondetects: incorporating low-level contaminants in risk assessment.
AB  - Low-level contaminants often are present below the detection or reporting limits
      of a laboratory, resulting in values reported as a nondetect or less-than. How
      can these values be summed along with detected concentrations to obtain a total,
      particularly when weighting factors such as toxic equivalence factors (TEFs) are
      used? The most common method employed by environmental scientists for summing
      nondetects along with detected values is to substitute one-half the detection
      limit for each nondetect. This substitution allows the least precise
      measurements, data with high detection limits, to have a strong influence on the
      resulting total amount. Substitution methods have repeatedly been shown to
      provide substandard results in studies over the last 2 decades. Here an
      alternative, the Kaplan-Meier (KM) method used throughout the fields of medical
      and industrial statistics, is used to obtain the total. KM estimates are far less
      affected by the least precise data than are estimates computed using
      substitution. No assumptions about the distribution of data (whether they follow
      a normal or other distribution) need be made. Direct application of KM to
      computation of toxicity equivalence concentrations (TECs) is shown.

PMID- 20821700
TI  - Reducing environmental impact of dairy cattle: a Czech case study.
AB  - We analyze options to reduce the future environmental impact of dairy cattle
      production, using an optimization model (DAIRY) applied to the Czech Republic.
      The DAIRY model can be used to calculate the overall environmental impact (OEI).
      We show that aquatic eutrophication and global warming are the 2 most important
      problems caused by dairy cattle. These problems are largely caused by nitrate
      leaching and emissions from animal housing. The DAIRY model indicates that the
      costs of reducing the OEI in 2020 by 20% are 12 MEuro. It is most cost effective
      to achieve this reduction by improving the efficiency of animal manure used as
      fertilizer. We tested the sensitivity of the model to assumptions about the
      following: 1) the relative importance of environmental problems as expressed in
      weighting factors, and 2) future cattle numbers and milk yield per milking cow.
      The first case indicates that disagreement on which problem is most urgent need
      not lead to disagreement about policies to be undertaken. Regardless of the
      weighting factors used, aquatic eutrophication and global warming are the most
      important problems. However, the overall costs of reducing the OEI differ with
      alternative sets of weighting factors, because the costs of emission reduction
      differ among pollutants. The second case shows that the DAIRY model results are
      more sensitive to changes in cattle numbers than to changes in milk yield. This
      study is the first integrated assessment of dairy cattle production for a Central
      European country and illustrates how systematic analyses may help to find optimal
      solutions.

PMID- 20821701
TI  - Multi-criteria decision analysis of test endpoints for detecting the effects of
      endocrine active substances in fish full life cycle tests.
AB  - Fish full life cycle (FFLC) tests are increasingly required in the
      ecotoxicological assessment of endocrine active substances. However, FFLC tests
      have not been internationally standardized or validated, and it is currently
      unclear how such tests should best be designed to provide statistically sound and
      ecologically relevant results. This study describes how the technique of multi
      criteria decision analysis (MCDA) was used to elicit the views of fish
      ecologists, aquatic ecotoxicologists and statisticians on optimal experimental
      designs for assessing the effects of endocrine active chemicals on fish. In MCDA
      qualitative criteria (that can be valued, but not quantified) and quantitative
      criteria can be used in a structured decision-making process. The aim of the
      present application of MCDA is to present a logical means of collating both data
      and expert opinions on the best way to focus FFLC tests on endocrine active
      substances. The analyses are presented to demonstrate how MCDA can be used in
      this context. Each of 3 workgroups focused on 1 of 3 species: fathead minnow
      (Pimephales promelas), Japanese medaka (Oryzias latipes), and zebrafish (Danio
      rerio). Test endpoints (e.g., fecundity, growth, gonadal histopathology) were
      scored for each species for various desirable features such as statistical power
      and ecological relevance, with the importance of these features determined by
      assigning weights to them, using a swing weighting procedure. The endpoint F1
      fertilization success consistently emerged as a preferred option for all species.
      In addition, some endpoints scored highly in particular species, such as
      development of secondary sexual characteristics (fathead minnow) and sex ratio
      (zebrafish). Other endpoints such as hatching success ranked relatively highly
      and should be considered as useful endpoints to measure in tests with any of the
      fish species. MCDA also indicated relatively less preferred endpoints in fish
      life cycle tests. For example, intensive histopathology consistently ranked low,
      as did measurement of diagnostic biomarkers, such as vitellogenin, most likely
      due to the high costs of these methods or their limited ecological relevance.
      Life cycle tests typically do not focus on identifying toxic modes and/or
      mechanisms of action, but rather, single chemical concentration-response
      relationships for endpoints (e.g., survival, growth, reproduction) that can be
      translated into evaluation of risk. It is, therefore, likely to be an inefficient
      use of limited resources to measure these mechanism-specific endpoints in life
      cycle tests, unless the value of such endpoints for answering particular
      questions justifies their integration in specific case studies.

PMID- 20821702
TI  - Integrated risk assessment of household chemicals and consumer products:
      addressing concerns about triclosan.

PMID- 20821703
TI  - Probabilistic application of a fugacity model to predict triclosan fate during
      wastewater treatment.
AB  - The fate and partitioning of the antimicrobial compound, triclosan, in wastewater
      treatment plants (WWTPs) is evaluated using a probabilistic fugacity model to
      predict the range of triclosan concentrations in effluent and secondary
      biosolids. The WWTP model predicts 84% to 92% triclosan removal, which is within
      the range of measured removal efficiencies (typically 70% to 98%). Triclosan is
      predominantly removed by sorption and subsequent settling of organic particulates
      during primary treatment and by aerobic biodegradation during secondary
      treatment. Median modeled removal efficiency due to sorption is 40% for all
      treatment phases and 31% in the primary treatment phase. Median modeled removal
      efficiency due to biodegradation is 48% for all treatment phases and 44% in the
      secondary treatment phase. Important factors contributing to variation in
      predicted triclosan concentrations in effluent and biosolids include influent
      concentrations, solids concentrations in settling tanks, and factors related to
      solids retention time. Measured triclosan concentrations in biosolids and non
      United States (US) effluent are consistent with model predictions. However,
      median concentrations in US effluent are over-predicted with this model,
      suggesting that differences in some aspect of treatment practices not
      incorporated in the model (e.g., disinfection methods) may affect triclosan
      removal from effluent. Model applications include predicting changes in
      environmental loadings associated with new triclosan applications and supporting
      risk analyses for biosolids-amended land and effluent receiving waters.

PMID- 20821704
TI  - Terrestrial ecological risk evaluation for triclosan in land-applied biosolids.
AB  - Triclosan is an antimicrobial compound found in many consumer products including
      soaps and personal care products. Most triclosan is disposed of down household
      drains, whereupon it is conveyed to wastewater treatment plants. Although a high
      percentage of triclosan biodegrades during wastewater treatment, most of the
      remainder is adsorbed to sludge, which may ultimately be applied to land as
      biosolids. We evaluated terrestrial ecological risks related to triclosan in land
      applied biosolids for soil microbes, plants, soil invertebrates, mammals, and
      birds. Exposures are estimated using a probabilistic fugacity-based model.
      Triclosan concentrations in biosolids and reported biosolids application rates
      are compiled to support estimation of triclosan concentrations in soil.
      Concentrations in biota tissue are estimated using an equilibrium partitioning
      model for plants and worms and a steady-state model for small mammals; the
      resulting tissue concentrations are used to model mammalian and avian dietary
      exposures. Toxicity benchmarks are identified from a review of published and
      proprietary studies. The results indicate that adverse effects related to soil
      fertility (i.e., disruption of nitrogen cycling) would be expected only under
      "worst-case" exposures, under certain soil conditions and would likely be
      transient. The available data indicate that adverse effects on plants,
      invertebrates, birds, and mammals due to triclosan in land-applied biosolids are
      unlikely.

PMID- 20821705
TI  - Probabilistic risk evaluation for triclosan in surface water, sediments, and
      aquatic biota tissues.
AB  - Triclosan, an antimicrobial compound used in personal care products, occurs in
      the aquatic environment due to residual concentrations in municipal wastewater
      treatment effluent. We evaluate triclosan-related risks to the aquatic
      environment, for aquatic and sediment-dwelling organisms and for aquatic-feeding
      wildlife, based on measured and modeled exposure concentrations. Triclosan
      concentrations in surface water, sediment, and biota tissue are predicted using a
      fugacity model parameterized to run probabilistically, to supplement the limited
      available measurements of triclosan in sediment and tissue. Aquatic toxicity is
      evaluated based on a species sensitivity distribution, which is extrapolated to
      sediment and tissues assuming equilibrium partitioning. A probabilistic wildlife
      exposure model is also used, and estimated doses are compared with wildlife
      toxicity benchmarks identified from a review of published and proprietary
      studies. The 95th percentiles of measured and modeled triclosan concentrations in
      surface water, sediment, and biota tissues are consistently below the 5th
      percentile of the respective species sensitivity distributions, indicating that,
      under most scenarios, adverse affects due to triclosan are unlikely.

PMID- 20821706
TI  - Bioaccessibility studies of ferro-chromium alloy particles for a simulated
      inhalation scenario: a comparative study with the pure metals and stainless
      steel.
AB  - The European product safety legislation, REACH, requires that companies that
      manufacture, import, or use chemicals demonstrate safe use and high level of
      protection of their products placed on the market from a human health and
      environmental perspective. This process involves detailed assessment of potential
      hazards for various toxicity endpoints induced by the use of chemicals with a
      minimum use of animal testing. Such an assessment requires thorough understanding
      of relevant exposure scenarios including material characteristics and intrinsic
      properties and how, for instance, physical and chemical properties change from
      the manufacturing phase, throughout use, to final disposal. Temporary or
      permanent adverse health effects induced by particles depend either on their
      shape or physical characteristics, and/or on chemical interactions with the
      particle surface upon human exposure. Potential adverse effects caused by the
      exposure of metal particles through the gastrointestinal system, the pulmonary
      system, or the skin, and their subsequent potential for particle dissolution and
      metal release in contact with biological media, show significant gaps of
      knowledge. In vitro bioaccessibility testing at conditions of relevance for
      different exposure scenarios, combined with the generation of a detailed
      understanding of intrinsic material properties and surface characteristics, are
      in this context a useful approach to address aspects of relevance for accurate
      risk and hazard assessment of chemicals, including metals and alloys and to avoid
      the use of in vivo testing. Alloys are essential engineering materials in all
      kinds of applications in society, but their potential adverse effects on human
      health and the environment are very seldom assessed. Alloys are treated in REACH
      as mixtures of their constituent elements, an approach highly inappropriate
      because intrinsic properties of alloys generally are totally different compared
      with their pure metal components. A large research effort was therefore conducted
      to generate quantitative bioaccessibility data for particles of ferro-chromium
      alloys compared with particles of the pure metals and stainless steel exposed at
      in vitro conditions in synthetic biological media of relevance for particle
      inhalation and ingestion. All results are presented combining bioaccessibility
      data with aspects of particle characteristics, surface composition, and barrier
      properties of surface oxides. Iron and chromium were the main elements released
      from ferro-chromium alloys upon exposure in synthetic biological media. Both
      elements revealed time-dependent release processes. One week exposures resulted
      in very small released particle fractions being less than 0.3% of the particle
      mass at acidic conditions and less than 0.001% in near pH-neutral media. The
      extent of Fe released from ferro-chromium alloy particles was significantly lower
      compared with particles of pure Fe, whereas Cr was released to a very low and
      similar extent as from particles of pure Cr and stainless steel. Low release
      rates are a result of a surface oxide with passive properties predominantly
      composed of chromium(III)-rich oxides and silica and, to a lesser extent, of
      iron(II,III)oxides. Neither the relative bulk alloy composition nor the surface
      composition can be used to predict or assess the extent of metals released in
      different synthetic biological media. Ferro-chromium alloys cannot be assessed
      from the behavior of their pure metal constituents.

PMID- 20821707
TI  - Particles, sweat, and tears: a comparative study on bioaccessibility of
      ferrochromium alloy and stainless steel particles, the pure metals and their
      metal oxides, in simulated skin and eye contact.
AB  - Ferrochromium alloys are manufactured in large quantities and placed on the
      global market for use as master alloys (secondary raw materials), primarily for
      stainless steel production. Any potential human exposure to ferrochromium alloy
      particles is related to occupational activities during production and use, with 2
      main exposure routes, dermal contact and inhalation and subsequent digestion.
      Alloy and reference particles exposed in vitro in synthetic biological fluids
      relevant for these main exposure routes have been investigated in a large
      research effort combining bioaccessibility; chemical speciation; and material,
      surface, and particle characteristics. In this paper, data for the dermal
      exposure route, including skin and eye contact, will be presented and discussed.
      Bioaccessibility data have been generated for particles of a ferrochromium alloy,
      stainless steel grade AISI 316L, pure Fe, pure Cr, iron(II,III)oxide, and
      chromium(III)oxide, upon immersion in artificial sweat (pH 6.5) and artificial
      tear (pH 8.0) fluids for various time periods. Measured released amounts of Fe,
      Cr, and Ni are presented in terms of average Fe and Cr release rates and amounts
      released per amount of particles loaded. The results are discussed in relation to
      bulk and surface composition of the particles. Additional information, essential
      to assess the bioavailability of Cr released, was generated by determining its
      chemical speciation and by providing information on its complexation and
      oxidation states in both media investigated. The effect of differences in
      experimental temperature, 30 degrees C and 37 degrees C, on the extent of metal
      release in artificial sweat is demonstrated. Iron was the preferentially released
      element in all test media and for all time periods and iron-containing particles
      investigated. The extent of metal release was highly pH dependent and was also
      dependent on the medium composition. Released amounts of Cr and Fe were very low
      (close to the limit of detection, <0.008% of particles released or dissolved as
      iron or chromium) for the alloy particles (ferrochromium alloy and stainless
      steel), the pure Cr particles, and the metal oxide particles. The released
      fraction of Cr (Cr/[Cr + Fe]) varied with the material investigated, the test
      medium, and the exposure time and cannot be predicted from either the bulk or the
      surface composition. Chromium was released as noncomplexed Cr(III) and in
      addition in very low concentrations (<3 microg/L). Nickel released was under the
      limit of detection (0.5 microg/L), except for ultrafine stainless steel particles
      (<10 microg/L). It is evident that media chemistry and material properties from a
      bulk and surface perspective, as well as other particle characteristics, and the
      chemical speciation of released metals have to be considered when assessing any
      potential hazard or risk induced by sparingly soluble metal or alloy particles.

PMID- 20821708
TI  - Regulatory aspects on the use of fish embryos in environmental toxicology.
AB  - Animal alternative tests are gaining serious consideration in an array of
      environmental sciences, particularly as they relate to sound management of
      chemicals and wastewater discharges. The ILSI Health and Environmental Sciences
      Institute and the European Centre for Ecotoxicology and Toxicology of Chemicals
      (ECETOC) held an International Workshop on the Application of the Fish Embryo
      Test in March, 2008. This relatively young discipline is following advances in
      animal alternatives for human safety sciences, and it is advisable to develop a
      broad comparison of how animal alternative tests involving fish are viewed in a
      regulatory context over a wide array of authorities or advising bodies. These
      include OECD, Western Europe, North America, and Japan. This paper summarizes
      representative practices from these regions. Presently, the global regulatory
      environment has varying stances regarding the protection of fish for use as an
      experimental animal. Such differences have a long-term potential to lead to a
      lack of harmony in approaches to fish toxicity testing, especially for chemicals
      in commerce across multiple geographic regions. Implementation of alternative
      methods and approaches will be most successful if accepted globally, including
      methods of fish toxicity testing. An important area for harmonization would be in
      the interpretation of protected and nonprotected life stages of fish. Use of fish
      embryos represent a promising alternative and allow bridging to more technically
      challenging alternatives with longer prospective timelines, including cell-based
      assays, ecotoxicogenomics, and QSARs.

PMID- 20821711
TI  - What the news media need from scientists.

PMID- 20821709
TI  - Are endocrine disruptors among the causes of the deterioration of aquatic
      biodiversity?
AB  - Exposure to environmental pollutants such as endocrine-disrupting compounds
      (EDCs) is now taken into account to explain partially the biodiversity decline of
      aquatic ecosystems. Much research has demonstrated that EDCs can adversely affect
      the endocrine system, reproductive health, and immune function in aquatic
      species. These toxicological effects include 1) interference with normal hormonal
      synthesis, release, and transport, 2) impairment of growth, development, and
      gonadal maturation, and 3) increased sensitivity to environmental stressors.
      Recent studies also have confirmed that EDCs have carcinogenic and mutagenic
      potential. In essence, these changes in physiological and biochemical parameters
      reflect, to some extent, some phenotypic characteristics of the deterioration of
      aquatic biodiversity. At present, evidence at the molecular level shows that
      exposure to EDCs can trigger genotoxicity, such as DNA damage, and can reduce
      genetic diversity. Field studies have also provided more direct evidence that
      EDCs contribute to the population decrease and biodiversity decline. Evolutionary
      toxicology and multigenerational toxicity tests have further demonstrated that
      EDCs can damage an organism's offspring and eventually likely lead to loss of
      evolutionary potential. Taken together, these results provide some basis for
      understanding the relationship between variety deterioration and EDC exposure. It
      is conceivable that there is a causal association between EDC exposure and
      variety deterioration of aquatic organisms.

PMID- 20821712
TI  - Statistics and ecotoxicology: shotgun marriage or enduring partnership?

PMID- 20821713
TI  - Incorporating environmental variability from rapid climate change into
      ecotoxicology tests.

PMID- 20821714
TI  - An ecological experimental framework for investigating and managing discharges
      from buildings using seawater as a coolant.

PMID- 20821715
TI  - The legacy lies in the sediments.

PMID- 20821716
TI  - Introduction to the special issue on environmental risk assessment of
      pharmaceuticals.

PMID- 20821717
TI  - Environmental risk assessment for the serotonin re-uptake inhibitor fluoxetine:
      Case study using the European risk assessment framework.
AB  - The serotonin re-uptake inhibitor fluoxetine was selected for an environmental
      risk assessment, using the most recent European guideline (EMEA 2006) within the
      European Union (EU)-funded Environmental Risk Assessment of Pharmaceuticals
      (ERAPharm) project due to its environmental persistence, acute toxicity to
      nontarget organisms, and unique pharmacokinetics associated with a readily
      ionizable compound. As a widely prescribed psychotropic drug, fluoxetine is
      frequently detected in surface waters adjacent to urban areas because municipal
      wastewater effluents are the primary route of entry to aquatic environments. In
      Phase I of the assessment, the initial predicted environmental concentration of
      fluoxetine in surface water (initial PEC(SW)) reached or exceeded the action
      limit of 10 ng/L, when using both a default market penetration factor and
      prescription data for Sweden, Germany, and the United Kingdom. Consequently, a
      Phase II risk assessment was conducted in which green algae were identified as
      the most sensitive species with a NOEC of <0.6 microg/L. From this value, a
      predicted no effect concentration for surface waters (PNEC(SW)) of 0.012 microg/L
      was derived. The PEC/PNEC ratio was above the trigger value of 1 in worst-case
      exposure scenarios indicating a potential risk to the aquatic compartment.
      Similarly, risks of fluoxetine for sediment-dwelling organisms could not be
      excluded. No risk assessment was conducted for the terrestrial compartment due to
      a lack of data on effects of fluoxetine on soil organisms. The need for a
      separate risk assessment for the main metabolite of fluoxetine, norfluoxetine,
      was not conducted because of a lack of fate and effect studies. Based on
      published data, fluoxetine and norfluoxetine appeared to have a low to moderate
      bioaccumulation potential, which should be confirmed in formal studies according
      to OECD guidelines. Exposure assessments for fluoxetine according to the current
      framework rely heavily on K(OC) and K(OW) values. This approach is problematic,
      because fluoxetine is predominantly a cationic substance at environmental pH
      values. Consequently, the fate of fluoxetine (and other ionic substances) cannot
      be predicted using partition coefficients established for nonionic compounds.
      Further, published estimates for partition coefficients of fluoxetine vary,
      resulting in considerable uncertainties in both the exposure and environmental
      risk assessments of fluoxetine.

PMID- 20821718
TI  - Environmental risk assessment of ivermectin: A case study.
AB  - The veterinary parasiticide ivermectin was selected as a case study compound
      within the project ERAPharm (Environmental Risk Assessment of Pharmaceuticals).
      Based on experimental data generated within ERAPharm and additional literature
      data, an environmental risk assessment (ERA) was performed mainly according to
      international and European guidelines. For the environmental compartments surface
      water, sediment, and dung, a risk was indicated at all levels of the tiered
      assessment approach. Only for soil was no risk indicated after the lower tier
      assessment. However, the use of effects data from additional 2-species and
      multispecies studies resulted in a risk indication for collembolans. Although
      previously performed ERAs for ivermectin revealed no concern for the aquatic
      compartment, and transient effects on dung-insect populations were not considered
      as relevant, the present ERA clearly demonstrates unacceptable risks for all
      investigated environmental compartments and hence suggests the necessity of
      reassessing ivermectin-containing products. Based on this case study, several
      gaps in the existing guidelines for ERA of pharmaceuticals were shown and
      improvements have been suggested. The action limit at the start of the ERA, for
      example, is not protective for substances such as ivermectin when used on
      intensively reared animals. Furthermore, initial predicted environmental
      concentrations (PECs) of ivermectin in soil were estimated to be lower than
      refined PECs, indicating that the currently used tiered approach for exposure
      assessment is not appropriate for substances with potential for accumulation in
      soil. In addition, guidance is lacking for the assessment of effects at higher
      tiers of the ERA, e.g., for field studies or a tiered effects assessment in the
      dung compartment.

PMID- 20821723
TI  - MRI of stroke using hyperpolarized 129Xe.
AB  - Because there is no background signal from xenon in biological tissue, and
      because inhaled xenon is delivered to the brain by blood flow, we would expect a
      perfusion deficit, such as is seen in stroke, to reduce the xenon concentration
      in the region of the deficit. Thermal polarization yields negligible xenon signal
      relative to hyperpolarized xenon; therefore, hyperpolarized xenon can be used as
      a tracer of cerebral blood flow. Using a rat permanent right middle cerebral
      artery occlusion model, we demonstrated that hyperpolarized (129)Xe MRI is able
      to detect, in vivo, the hypoperfused area of focal cerebral ischemia, that is the
      ischemic core area of stroke. To the best of our knowledge, this is the first
      time that hyperpolarized (129)Xe MRI has been used to explore normal and abnormal
      cerebral perfusion. Our study shows a novel application of hyperpolarized (129)Xe
      MRI for imaging stroke, and further demonstrates its capacity to serve as a
      complementary tool to proton MRI for the study of the pathophysiology during
      brain hypoperfusion.

PMID- 20821726
TI  - Synchronous acquisition of hyperpolarised 3He and 1H MR images of the lungs -
      maximising mutual anatomical and functional information.
AB  - The development of hybrid medical imaging scanners has allowed imaging with
      different detection modalities at the same time, providing different anatomical
      and functional information within the same physiological time course with the
      patient in the same position. Until now, the acquisition of proton MRI of lung
      anatomy and hyperpolarised gas MRI of lung function required separate breath-hold
      examinations, meaning that the images were not spatially registered or temporally
      synchronised. We demonstrate the spatially registered concurrent acquisition of
      lung images from two different nuclei in vivo. The temporal and spatial
      registration of these images is demonstrated by a high degree of mutual
      consistency that is impossible to achieve in separate scans and breath holds.

PMID- 20821727
TI  - Control of Schistosoma mansoni egg-induced inflammation by IL-4-responsive
      CD4(+)CD25(-)CD103(+)Foxp3(-) cells is IL-10-dependent.
AB  - Host protection to helminth infection requires IL-4 receptor alpha chain (IL
      4Ralpha) signalling and the establishment of finely regulated Th2 responses. In
      the current study, the role of IL-4Ralpha-responsive T cells in Schistosoma
      mansoni egg-induced inflammation was investigated. Egg-induced inflammation in IL
      4Ralpha-responsive BALB/c mice was accompanied with Th2-biased responses, whereas
      T-cell-specific IL-4Ralpha-deficient BALB/c mice (iLck(cre)Il4ra(-) (/lox))
      developed Th1-biased responses with heightened inflammation. The proportion of
      Foxp3(+) Treg in the draining LN of control mice did not correlate with the
      control of inflammation and was reduced in comparison to T-cell-specific IL
      4Ralpha-deficient mice. This was due to IL-4-mediated inhibition of
      CD4(+)Foxp3(+) Treg conversion, demonstrated in adoptively transferred Rag2(-)
      (/) (-) mice. Interestingly, reduced footpad swelling in Il4ra(-) (/lox) mice was
      associated with the induction of IL-4 and IL-10-secreting CD4(+)CD25(
      )CD103(+)Foxp3(-) cells, confirmed in S. mansoni infection studies. Transfer of
      IL-4Ralpha-responsive CD4(+)CD25(-)CD103(+) cells, but not CD4(+)CD25(high) or
      CD4(+)CD25(-)CD103(-) cells, controlled inflammation in iLck(cre)Il4ra(-) (/lox)
      mice. The control of inflammation depended on IL-10, as transferred CD4(+)CD25(
      )CD103(+) cells from IL-10-deficient mice were not able to effectively
      downregulate inflammation. Together, these results demonstrate that IL-4
      signalling in T cells inhibits Foxp3(+) Treg in vivo and promotes CD4(+)CD25(
      )CD103(+)Foxp3(-) cells that control S. mansoni egg-induced inflammation via IL
      10.

PMID- 20821728
TI  - Influenza matrix 1-specific human CD4+ FOXP3+ and FOXP3(-) regulatory T cells can
      be detected long after viral clearance.
AB  - Control and termination of infection with Influenza A virus is associated with
      increased IL-10 production in mouse models. Notably, IL-10 can be produced by
      Treg. Therefore, we investigated whether the population of IL-10-producing
      influenza-specific CD4(+) T cells comprised Treg as they are potent suppressors
      of the adaptive immune response. Influenza-specific IL-10-producing T cells were
      detected in all human donors displaying influenza-specific immunity. Isolation of
      Matrix 1 protein-specific IL-10-producing T-cell clones revealed that a
      substantial proportion of these T-cell clones displayed the capacity to suppress
      effector cells, functionally identifying them as Treg. Both FOXP3(+) and FOXP3(-)
      CD4(+) Treg were isolated and all were able to exert their suppressive capacity
      when stimulated with cognate antigen, including influenza virus-infected cells.
      In vitro suppression was not mediated by IL-10 but involved interference with the
      IL-2 axis. The isolated Treg suppressed amongst others the IL-2 production of
      influenza-specific T-helper cells as well as partially prevented the upregulation
      of the high-affinity IL-2 receptor on CD8 effector cells. So far the induction of
      virus-specific Treg has only been studied in the context of chronic viral
      infections. This study demonstrates that virus-specific Treg can also be induced
      by viruses that are rapidly cleared in humans.

PMID- 20821729
TI  - Concomitant type I IFN receptor-triggering of T cells and of DC is required to
      promote maximal modified vaccinia virus Ankara-induced T-cell expansion.
AB  - Virus-induced expansion of CD8(+) T cells may be promoted by type I IFN receptor
      (IFNAR)-triggering of T cells, depending on the pathogen tested. We studied
      modified vaccinia virus Ankara (MVA), a promising vaccine vector candidate, which
      was derived from conventional vaccinia virus (VACV) by more than 570 consecutive
      in vitro passages. In adoptive transfer experiments, we verified that VACV
      expressing the gp33 epitope of lymphocytic choriomeningitis virus (VACV(gp33))
      induced largely IFNAR-independent expansion of gp33-specific T cells. On the
      contrary, MVA(gp33)-induced T-cell expansion was IFNAR dependent. Interestingly,
      under the latter conditions, T-cell activation was IFNAR independent, whereas T
      cell apoptosis was enhanced in the absence of IFNAR. To address whether MVA
      induced T-cell expansion was solely affected by IFNAR-triggering of T cells,
      expansion of endogenous T cells was studied in conditional mice with a T-cell- or
      DC-specific IFNAR deletion. Interestingly, both mouse strains showed moderately
      reduced T-cell expansion, whereas mice with a combined T-cell- and DC-specific
      IFNAR ablation showed massively reduced T-cell expansion similar to that of
      IFNAR(-/-) mice. These results are compatible with the model that IFN-inducing
      viruses such as MVA confer virus-specific CD8(+) T-cell expansion by concomitant
      IFNAR-triggering of DC and of T cells.

PMID- 20821730
TI  - A dynamic immunological synapse mediates homeostatic TCR-dependent and 
      independent signaling.
AB  - For homeostasis, T cells integrate non-cognate TCR-dependent and -independent
      signals to survive and weakly proliferate. In contrast to antigen-specific,
      stable, and long-lived contacts, signaling in short-lived homeostatic
      interactions depends upon the coordination of ongoing T-cell migration on the
      surface of DC and signaling at the cell-cell junction. To mimic peripheral
      tissues and analyze how T-cell migration and cell-cell signaling are integrated,
      we used live-cell imaging and 3-D reconstruction of fixed conjugates between
      DO11.10 T cells and DC in 3-D low-density collagen matrices. T cells
      simultaneously maintained amoeboid migration and polarized towards the DC,
      leading to a fully dynamic interaction plane that delivered signals for
      homeostatic T-cell survival and proliferation. The contact plane comprised three
      zones, the actin-rich leading edge poor in signal but driving migration, a mid
      zone mediating TCR/MHC-induced signal associated with proliferation, and the rear
      uropod mediating predominantly MHC-independent signals. Thus a dynamic
      immunological synapse with distinct signaling sectors enables moving T cells to
      serially sample resident tissue cells and acquire molecular information "en
      passant".

PMID- 20821732
TI  - Proteomic analysis of germinating urediniospores of Phakopsora pachyrhizi, causal
      agent of Asian soybean rust.
AB  - Phakopsora pachyrhizi is an obligate pathogen that causes Asian soybean rust.
      Asian soybean rust has an unusually broad host range and infects by direct
      penetration through the leaf cuticle. In order to understand the early events in
      the infection process, it is important to identify and characterize proteins in
      P. pachyrhizi. Germination of the urediniospore is the first stage in the
      infection process and represents a critical life stage applicable to studies with
      this obligate pathogen. We have applied a 2-DE and MS approach to identify 117
      proteins from the National Center of Biotechnology Information nonredundant
      protein database and a custom database of Basidiomycota EST sequences. Proteins
      with roles in primary metabolism, energy transduction, stress, cellular
      regulation and signaling were identified in this study. This data set is
      accessible at http://world-2dpage.expasy.org/repository/database=0018.

PMID- 20821731
TI  - Tolerogenic plasmacytoid DC.
AB  - Plasmacytoid DC (pDC) are type-I IFN-producing cells known for their capacity to
      promote anti-viral innate and adaptive immune responses. Despite their potent
      anti-viral function, when compared with conventional DC, pDC exhibit poor
      immunostimulatory ability and their interaction with T cells often favors the
      generation of Treg. pDC are activated primarily in response to ssRNA and ssDNA
      through TLR7 and TLR9, respectively, but also through TLR-independent mechanisms.
      Non-lymphoid tissue pDC, such as those residing in the airways, gut, and liver,
      play a significant role in regulating mucosal immunity and are critical for the
      development of tolerance to inhaled or ingested antigens. Herein we discuss
      properties that define tolerogenic pDC and how their unique characteristics
      translate into an ability to regulate immunity and promote the development of
      tolerance. We cover the importance of pDC during intrathymic Treg development and
      the maintenance of peripheral tolerance, as well as their regulatory role in
      transplantation, autoimmunity, and cancer. We highlight recent findings regarding
      danger-associated molecular pattern and PAMP signaling in the regulation of pDC
      function, and how the ability of pDC to promote tolerance translates into the
      potential clinical applications of these cells as therapeutic targets to regulate
      immune reactivity.

PMID- 20821733
TI  - A novel reactive ester derivative of biotin with reduced membrane permeability
      for in vivo biotinylation experiments.
AB  - The in vivo perfusion of rodent models of disease with biotin derivatives and the
      subsequent comparative proteomic analysis of healthy and diseased tissues
      represent a promising methodology for the identification of vascular accessible
      biomarkers. A novel, triply charged biotinylation reagent, NHS-beta-Ala-(L
      Asp)(3)-biotin, was synthesized and validated in terms of its applicability for
      in vivo protein biotinylation. Compared to sulfo-NHS-LC-biotin, NHS-beta-Ala-(L
      Asp)(3)-biotin exhibited a reduced membrane permeability and a preferential
      labeling of proteins localized in compartments readily accessible in vivo from
      the vasculature.

PMID- 20821734
TI  - Tat acetylation regulates its actions on microtubule dynamics and apoptosis in T
      lymphocytes.
AB  - The transactivator protein Tat of human immunodeficiency virus type 1 (HIV-1) is
      known to suppress microtubule dynamics and thereby trigger apoptosis in T
      lymphocytes. These actions of Tat constitute one of the major mechanisms for the
      massive destruction of T lymphocytes associated with the acquired
      immunodeficiency syndrome. Herein, we show that Tat acetylation at lysine-28
      (K28) enhances its interaction with microtubules and increases its activity to
      promote microtubule assembly, by lowering the critical concentration of tubulin
      for polymerization into microtubules. In addition, K28 acetylation enhances the
      ability of Tat to stabilize microtubules, leading to increased apoptosis in T
      lymphocytes. Our data further reveal that Tat acetylation at K28 stimulates its
      activity to induce the translocation of Bim, a pro-apoptotic protein of the Bcl-2
      family, from microtubules to mitochondria. These findings provide the first
      evidence that Tat acetylation regulates its actions on microtubule dynamics and
      apoptosis, in addition to the regulation of its transactivation activity.

PMID- 20821735
TI  - The analysis of glycosylation: a continued need for high pH anion exchange
      chromatography.
AB  - An appreciation of the structures of the oligosaccharide chains which become
      attached to biomolecules (the process known as glycosylation), and their
      relevance to the biological function of the molecule concerned, has progressed
      rapidly in recent years with developments in site-selective protein
      glycosylation, oligosaccharide synthesis and in vivo targeting of
      oligosaccharides. These developments have necessitated the parallel development
      of effective analytical tools for the determination of the structures of
      glycosylation. The conclusion of studies in the 1980s and 1990s was that high pH
      anion exchange chromatography (HPAEC) was the most effective HPLC mode for the
      analysis of glycosylation. It allowed the fractionation of complex mixtures of
      monosaccharides or oligosaccharides, the latter in terms of charge, size,
      composition, anomerity and intra-chain linkages. This review reinvestigates
      whether HPAEC still appears to offer the most effective means of analysing
      glycosylation.

PMID- 20821736
TI  - Eating disorders, obesity and addiction.
AB  - An addiction model of both eating disorders and obesity has received increasing
      attention in the popular and scientific literature. The addiction is viewed as a
      brain disease that must be directly targeted if treatment is to succeed. Evidence
      from laboratory feeding studies, epidemiology, genetic and familial research,
      psychopathological mechanisms, and treatment outcome research on cognitive
      behaviour therapy (CBT) is inconsistent with the clinical validity or utility of
      the addiction model of eating disorders. Neurobiological research has shown
      commonalities in brain reward processes between obesity and substance abuse
      disorders. Yet emphasis on apparent similarities overlooks important differences
      between obesity and drug addiction. Interest in obesity as a brain disease should
      not detract from a public health focus on the 'toxic food environment' that is
      arguably responsible for the obesity epidemic and related nutrition-based chronic
      disease.

PMID- 20821737
TI  - The diagnosis of eating disorders in adults with learning disabilities:
      Conceptualisation and implications for clinical practice.
AB  - OBJECTIVE: The literature suggests that less attention has been afforded to
      eating disorders (EDs) in adults with learning disabilities (LDs) than in adults
      of normal intellect. This review aimed to examine the methods, prevalence and
      implications of an ED diagnosis in adults with LDs. METHOD: Key texts, journals
      and online databases were searched for literature examining disordered eating in
      adults with LDs. RESULTS: A review of the extant literature revealed that a range
      of dysfunctional eating behaviours have been classified as 'eating disorders' and
      highlighted a lack of clarity about the distinction between feeding and EDs. A
      small body of research suggests that some individuals with LDs show the emotional
      and cognitive characteristics of typical EDs. DISCUSSION: The lack of consensus
      about conceptualisation, assessment, diagnosis and treatment of EDs in
      individuals with LDs needs to be addressed in order to aid awareness and enhance
      clinical approaches for this population.

PMID- 20821738
TI  - Psychological variables impacting weight gain rapidity in adolescents
      hospitalized for eating disorders.
AB  - OBJECTIVE: This prospective study examined whether psychological variables
      related to the transdiagnostic theory of eating disorders measured at admission
      predicted length of time to reach 85 per cent of ideal body weight (IBW) among
      underweight adolescents hospitalized for an eating disorder. METHOD: Thirty-three
      girls (aged 12-17) weighing below 85 per cent of IBW, admitted to an inpatient
      and/or partial hospitalization eating disorder programme completed self-report
      measures at admission. Cox regression tested whether scores on admission measures
      predicted time to reach 85 per cent of IBW. RESULTS: After controlling for IBW at
      admission, higher self-esteem and lower perfectionism predicted shorter time to
      reach 85 per cent of IBW, with emotion regulation as a marginally significant
      predictor. CONCLUSION: Self-esteem and perfectionism may be predictors of
      responsiveness to weight-gain efforts during hospitalization. Further studies are
      necessary to determine whether these variables might be appropriate targets for
      intervention to promote weight gain in underweight girls with eating disorders.

PMID- 20821739
TI  - Olfactory deficits in patients with anorexia nervosa.
AB  - BACKGROUND: Patients with anorexia nervosa (AN) often show gastrointestinal
      symptoms and have altered gastrointestinal functions. Olfaction is part of the
      predigestive function and plays an important role in the selection of food and
      the control of food intake. The question arises if patients with eating disorders
      have changes in olfactory functions as well. The aim of this study was to compare
      olfactory functions in patients with AN and controls using the Sniffin' sticks.
      METHOD: We studied 19 patients with AN, restricting type (10 patients) and binge
      eating/purging type (9 patients) and 21 healthy controls matched by age. For
      evaluation of the severity of AN we used the Eating Disorder Inventory-2 (EDI-2).
      RESULTS: Differences were found in odour identification with patients with AN
      having lower scores and there was a significant correlation between results in
      this subtest and BMI. There were no differences in odour threshold, odour
      discrimination and overall performance. There was no correlation between test
      results and EDI-2 scores. We did not find differences between subtypes of AN.
      CONCLUSIONS: Larger and more homogenous samples are needed to gain a better
      understanding of degree and type of olfactory deficits in AN-patients with
      possible consequences for refeeding therapy.

PMID- 20821740
TI  - Perspectives on eating disorders and service provision: A qualitative study of
      healthcare professionals.
AB  - The study examined healthcare professionals' perspectives of eating disorder
      patients and services. Qualitative semi-structured interviews were conducted with
      18 healthcare professionals resulting in two themes. First, the practical
      difficulties of meeting the complex service needs of people with eating disorders
      were illustrated. Second, staff recognised patient diversity and the consequent
      need for individualised interventions. Services are frustrated in meeting patient
      needs due to complex resource limitations, which do not amount only to lack of
      funding. Rather than eating disordered patients being viewed as 'difficult', as
      reported in previous qualitative research, they are only difficult in a context
      of limited resources.

PMID- 20821741
TI  - The incidence of anorexia nervosa in Netherlands Antilles immigrants in the
      Netherlands.
AB  - OBJECTIVE: Previously we found that the incidence of anorexia nervosa (AN) in the
      general population was much lower in the Netherlands Antilles than in the
      Netherlands. As a follow-up we compared the incidence of AN in the Netherlands in
      persons from the Netherlands Antilles to native Dutch. METHOD: A national
      register of psychiatric hospital admissions was screened for cases of AN.
      Incidence rates (IR) and incidence rate ratios (IRR) were computed. RESULTS: The
      IR of AN was 1.32 per 100 000 person years (95% confidence interval (CI): 0.53
      2.71) for Netherlands Antilleans and 1.09 (95% CI: 1.04-1.15) for native Dutch.
      The age- and sex-adjusted IRR was 1.21 (95% CI: 0.58-2.54). CONCLUSION: Contrary
      to the Netherlands Antilles, in the Netherlands AN is as common among Netherlands
      Antilleans as among native Dutch. Exposure to the Western idealization of
      thinness is a risk factor for the development of AN, possibly in interaction with
      migration-related stress.

PMID- 20821742
TI  - Bevin Boys.

PMID- 20821745
TI  - Magnetically guided lentiviral-mediated transduction of airway epithelial cells.
AB  - BACKGROUND: Lentiviral (LV) vectors are able to only slowly and inefficiently
      transduce nondividing cells such as those of the airway epithelium. To address
      this issue, we have exploited the magnetofection technique in in vitro models of
      airway epithelium. METHODS: Magnetofectins were formed by noncovalent interaction
      between LV particles and polycation-coated iron oxide nanoparticles. Efficiency
      of LV-mediated transduction (as evaluated through green fluorescent protein (GFP)
      expression by cytofluorimetric analysis) was measured in bronchial epithelial
      cells in the presence or absence of a magnetic field. Cytotoxicity was evaluated
      by lactate dehydrogenase (LDH) release; cell monolayer integrity by measurement
      of transepithelial resistance (TER) and evaluation of correct zonula occludens-1
      (ZO-1) localization at tight junctions (TJs) by immunofluorescence and confocal
      microscopy. RESULTS: In nonpolarized cells, magnetofectins enhanced LV-mediated
      transduction at multiplicity of infection (MOI) of 50 up to 3.9-fold upon a 24-h
      incubation, to levels that approached those achieved at MOI of 200 for LV alone,
      in the presence or absence of the magnetic field. Magnetofection significantly
      increased the percentage of transduced cells up to 186-fold already after 15 min
      of incubation. In polarized cells, magnetofection increased GFP+ cells up to 24
      fold compared to LV alone. Magnetofection did not enhance LDH release and
      slightly altered TER but not ZO-1 localization at the TJs. CONCLUSIONS: We
      conclude that magnetofection can facilitate in vitro LV-mediated transduction of
      airway epithelial cells, in the absence of overt cytotoxicity and maintaining
      epithelial integrity, by lowering the necessary vector dose and reducing the
      incubation time required to achieve efficient transduction.

PMID- 20821744
TI  - Persistent interferon transgene expression by RNA interference-mediated silencing
      of interferon receptors.
AB  - BACKGROUND: The in vivo half-life of interferons (IFNs) is very short, and its
      extension would produce a better therapeutic outcome in IFN-based therapy.
      Delivery of IFN genes is one solution for providing a sustained supply. IFNs have
      a variety of functions, including the suppression of transgene expression,
      through interaction with IFN receptors (IFNRs). This suppression could prevent
      IFNs from being expressed from vectors delivered. Silencing the expression of
      IFNAR and IFNGR, the receptors for type I and II IFNs, respectively, in cells
      expressing IFNs may prolong transgene expression of IFNs. METHODS: Mouse melanoma
      B16-BL6 cells or mouse liver were selected as a site expressing IFNs (not a
      target for IFN gene therapy) and IFN-expressing plasmid DNA was delivered with or
      without small interfering RNA (siRNA) targeting IFNRs. RESULTS: Transfection of
      B16-BL6 cells with siRNA targeting IFNAR1 subunit (IFNAR1) resulted in the
      reduced expression of IFNAR on the cell surface. This silencing significantly
      increased the IFN-beta production in cells that were transfected with IFN-beta
      expressing plasmid DNA. Similar results were obtained with the combination of IFN
      gamma and IFNGR. Co-injection of IFN-beta-expressing plasmid DNA with siRNA
      targeting IFNAR1 into mice resulted in sustained plasma concentration of IFN
      beta. CONCLUSIONS: These results provide experimental evidence that the RNAi
      mediated silencing of IFNRs in cells expressing IFN, such as hepatocytes, is an
      effective approach for improving transgene expression of IFNs when their
      therapeutic target comprises cells other than those expressing IFNs.

PMID- 20821746
TI  - Transcriptional regulation of inducible nitric oxide synthase gene therapy:
      targeting early stage and advanced prostate cancer.
AB  - BACKGROUND: Using the tumour type specific human osteocalcin (hOC) promoter, we
      have previously reported strong promoter activation in hormone independent
      prostate cancer cells in vitro. In the present study, we present a comparative
      study of the tissue specific promoter prostate specific membrane antigen (PSMA),
      and the tumour-type specific hOC promoter driving the inducible nitric oxide
      synthase (iNOS) transgene using both in vitro and in vivo models. METHODS: In
      vitro cytotoxicity was assessed by clonogenic assay. Quantification of nitric
      oxide expression was determined by the Griess test. In vivo anti-tumour efficacy
      was determined by tumour growth delay following direct intra-tumoural injection
      of the constructs into PC3 xenografts. In addition, tumours were dissected post
      mortem and examined for morphological differences as well as changes in apoptotic
      protein expression. RESULTS: PSMA/iNOS produced cytotoxicity in both androgen
      dependant and independent cell lines. Nitric oxide quantification confirmed that
      increased cytotoxicity was directly associated with nitric oxide production.
      Tumour growth delays were observed in all groups treated with the iNOS-expressing
      constructs ranging from 10.7 days for the hOC/iNOS single dose treatment group to
      a maximum of 52.2 days for the hOC/iNOS multiple dose group. Intra-tumoural
      assessment of iNOS and cleaved poly (ADP-ribose) polymerase protein expression
      demonstrated a significant up-regulation of both proteins, indicating
      cytotoxicity mediated through the intrinsic apoptotic pathway. CONCLUSIONS:
      Highly significant tumour growth delay coupled with no detrimental side-effects
      were observed following treatment with the PSMA/iNOS and hOC/iNOS constructs. We
      consider that these findings provide a basis for the development of systemically
      delivered PSMA/iNOS or hOC/iNOS targeting early stage and advanced prostate
      cancer.

PMID- 20821747
TI  - RH10 provides superior transgene expression in mice when compared with natural
      AAV serotypes for neonatal gene therapy.
AB  - BACKGROUND: Neonatal gene therapy is a promising strategy for treating diseases
      diagnosed before or shortly after birth. Early and long-term expression of
      therapeutic proteins may limit the consequences of genetic mutations and result
      in a potential 'cure'. Adeno-associated viral vectors have shown promise in many
      areas of adult gene therapy but their properties have not been systematically
      investigated in the neonate. METHODS: In these studies, using a constitutive
      promoter expressing luciferase, animals were administered one of ten serotypes of
      adeno-associated virus (AAV) on the second day of life. Examination of
      expression, organ growth and vector distribution, maintenance of expression and
      copy number were measured. RESULTS: All serotypes demonstrated expression and, in
      general, transduction of all organs within 3 days, albeit with different
      biodistribution patterns and expression levels. The highest expression was
      detected with AAVrh10, whereas the lowest was detected with AAV4. Expression and
      genomes declined with growth over the first 10 weeks of life; thereafter, to day
      100, expression and genomes remained relatively stable. With the highest
      expressing vectors, whole animal expression at 100 days declined to approximately
      10% of that detected on the fifth day. AAVrh10 maintained the highest expression
      level and copy number throughout these studies. CONCLUSIONS: The impact of tissue
      and organ growth on the stability of AAV expression will be important if neonatal
      gene transfer is to be considered as a modality for human gene therapy. Although
      all vectors did demonstrate expression, rh10 holds the greater promise of the
      vectors tested to maintain copy number in both mitotic and post-mitotic tissues.

PMID- 20821748
TI  - An hydrophobically modified arginine peptide vector system effectively delivers
      DNA into human mesenchymal stem cells and maintains transgene expression with
      differentiation.
AB  - BACKGROUND: The ability of human mesenchymal stem cells (hMSCs) to differentiate
      into specific cells holds promise for therapeutic use in cell- or gene-based
      therapy. Genetic modification of hMSCs by introduction of therapeutic genes is an
      important tool for successful cell-mediated gene therapy. Similar to most primary
      cells, hMSCs are difficult to transfect with currently available gene delivery
      methods. Viral vectors are the most efficient DNA delivery system in stem cells.
      However, the use of viral vectors has disadvantages involving safety. To overcome
      these problems, nonviral gene delivery has been studied as an alternative
      strategy, and the cationic peptide was an efficient vector for transfecting
      various mammalian cell types. However, little is known about the capacity of this
      delivery method to transfect to hMSCs. In the present study, we examined the use
      of a short arginine peptide as a carrier for DNA delivery in hMSCs. METHODS:
      Plasmids containing the enhanced green fluorescent protein (EGFP) were
      transfected into hMSCs by arginine peptide in vitro. pEGFP delivery and EGFP
      expression were assessed by the fluorescence-activated cell sorting technique.
      RESULTS: The hydrophobically modified arginine peptide, palmitic acid-R15 (PA
      R15), formed a condensed complex with DNA and successfully delivered the gene
      into hMSCs without compromising cell survival rate. Complexes readily
      internalized into hMSCs after a 4 h incubation, and PA-R15 showed higher cellular
      uptake compared to the unmodified arginine peptide (R15). In addition,
      transfected cells retained their stem cell properties, including the ability to
      differentiate into adipogenic and osteogenic lineages. Moreover, the
      erythropoietin (EPO) gene was successfully transfected into hMSCs and the cells
      produced EPO for 4 weeks. CONCLUSIONS: Hydrophobically modified arginine peptides
      are promising candidates with low toxicity. They comprise efficient nonviral gene
      delivery vectors for hMSCs and these may be used as a potential tool for basic
      research and the therapeutic application of hMSCs.

PMID- 20821751
TI  - You can win by losing: p53 mutations in rhabdomyosarcomas.
AB  - Rhabdomyosarcomas are soft tissue sarcomas of mesenchymal origin. Unlike
      rhabdomyosarcomas observed in paediatric patients which typically respond well to
      chemotherapeutic treatment, adults generally present with pleomorphic
      rhabdomyosarcomas that are typically associated with poor prognosis. Therefore,
      understanding the molecular biology that gives rise to pleomorphic
      rhabdomyosarcomas is critical. In this issue of The Journal of Pathology, Doyle
      and colleagues have generated elegant tissue-specific Cre/loxP-dependent mouse
      models that mimic pleomorphic rhabdomyosarcoma development in humans. In this
      report, the authors employed KRas(G12V)-expressing mouse models that
      concomitantly either express mutant p53 (p53R172H) or have deleted the p53 gene.
      Mice that express mutant p53 have decreased survival with development of
      aggressive metastases as compared to mice that have simply lost wild-type p53.
      The data presented herein provide the first in vivo evidence that in
      rhabdomyosarcomas, expression of mutant p53 results in a more aggressive p53R172H
      dependent gain-of-function phenotype.

PMID- 20821752
TI  - Protein kinase inhibitors can control the progression of endometriosis in vitro
      and in vivo.
AB  - Endometriosis affects 6-10% of women in their reproductive years, causing chronic
      pelvic pain and infertility. Its pathogenesis remains poorly understood and
      current treatments, based on hormonal therapy or surgery, are often insufficient.
      The purpose of our study was to investigate the role of the ERK pathway in the
      development of endometriosis and to test the effects of protein kinase inhibitors
      on the proliferation of endometriotic cells in vitro and in vivo. We studied ex
      vivo human endometrial and endometriotic cells in culture. Stromal and epithelial
      cells were extracted from endometrial and endometriotic biopsies from patients
      with endometriosis and from patients without endometriosis. The ERK pathway was
      explored by western blot on cell lysates and by ELISA on total crushed specimens
      of endometrium. Cells in culture were treated with A771726, PD98059, and U0126.
      Human endometriotic lesions were implanted in nude mice. Mice were treated with
      A771726, leflunomide, PD98059, U0126 or PBS during 2 weeks before sacrifice and
      extraction of the endometriotic implants for histological examination. We found
      that the ERK pathway was significantly activated in endometriotic cells and in
      endometrial cells from patients with endometriosis compared to endometrial cells
      of control patients, both by ELISA and by western blot. This phenomenon was
      associated with an increased proliferation of endometriotic cells compared to
      endometrial cells. Treating endometriotic cells with A771726, PD98059 or U0126
      abrogated the phosphorylation of ERK and significantly decreased the cellular
      proliferation in vitro. In vivo, A771726, leflunomide, PD98059, and U0126
      controlled the growth of endometriotic implants in the mouse model of
      endometriosis. Our study shows that protein kinase inhibitors could be new
      candidates to treat endometriosis. However, further studies are needed to
      evaluate their effects and tolerability in humans.

PMID- 20821753
TI  - Critical appraisal of single port access cholecystectomy.

PMID- 20821754
TI  - Origin of presacral local recurrence after rectal cancer treatment.

PMID- 20821755
TI  - Rectal washout and local recurrence of cancer after anterior resection.

PMID- 20821756
TI  - Closure of the LAPSIS trial.

PMID- 20821759
TI  - Hierarchical hollow Co9S8 microspheres: solvothermal synthesis, magnetic,
      electrochemical, and electrocatalytic properties.
AB  - A simple solvothermal route in a binary solution of triethylenetetramine (TETA)
      and deionized water (DIW) has been used to synthesize hierarchical hollow
      Co(9)S(8) microspheres with high surface area (80.38 m(2) g(-1)). An appropriate
      volume ratio of TETA:DIW has been found to be essential for the formation of
      hollow Co(9)S(8) microspheres. The magnetic study indicated that the Co(9)S(8)
      hollow microspheres are paramagnetic at high temperature and antiferromagnetic at
      low temperature. The oxygen reduction reaction experiments demonstrated that the
      onset potential of the Co(9)S(8) sample is 0.88 V, which is comparable to the
      value predicted for Co(9)S(8) (0.74 V) from the theoretical simulation. The
      discharge capability of Co(9)S(8) hollow microspheres as cathode materials for
      lithium ion batteries and their electrocatalytic activity for the oxygen
      reduction reaction (ORR) have been studied.

PMID- 20821761
TI  - Nonpolar gemini amphiphiles self-assemble into stacked layers of nano-objects.
AB  - Fluorine in bloom: A nonpolar fluorocarbon/hydrocarbon tetrablock self-assembles
      into a first monolayer consisting of an array of densely packed discrete circular
      surface micelles (dark); this layer is surmounted by a second layer of such nano
      objects (light).

PMID- 20821762
TI  - Electronic tuning of a carbene center via remote chemical induction, and relevant
      effects in catalysis.
AB  - The present report develops the idea that an N-heterocyclic carbene incorporating
      a remote anionic functionality--here, a malonate group--as a backbone component
      of its heterocyclic framework, can be "post-functionalized" directly from its
      transition-metal complexes, upon simple addition of a variety of electrophiles
      interacting directly with the malonate group in the outer coordination sphere.
      From a palette of selected electrophilic reagents, it was thus possible to
      modulate the electronic donor properties of the carbene center over a rather
      broad range. Both the zwitterionic complex [Rh{malo-NHC}(cod)] and the cationic
      derivatives [Rh{malo-NHC(E)}(cod)](+) (where "malo-NHC(E)" represents the ligand
      modified by a selected electrophile "E") were used as pre-catalysts in two types
      of catalytic reactions, namely, the polymerization of phenylacetylene and the
      hydroboration of styrene. The results indicate that, in both cases, the
      zwitterionic species is by far the best catalyst, whereas a decrease in the
      ligand donicity induced by the added electrophile results in a concomitant
      reduction of catalytic activity. Apparent deviations to such a trend in the case
      of the hydroboration of styrene were rationalized in terms of an interaction
      between the reactive catecholborane substrate and the remote functionality of the
      N-heterocyclic carbene leading to an in situ modification of the nature of the
      active species. These observations serve as a useful basis to define the scope
      and limitations of the present conceptual approach in catalysis.

PMID- 20821760
TI  - Localized deposition of Au nanoparticles by direct electron transfer through
      cellobiose dehydrogenase.
AB  - Cellobiose dehydrogenase (CDH) is a fascinating extracellular fungal enzyme that
      consists of two domains, one carrying a flavin adenine dinucleotide (FAD) and the
      other a cytochrome-type heme b group as cofactors. The two domains are
      interconnected by a linker and electrons can shuttle from the FAD to the heme
      group by intramolecular electron transfer. Electron transfer between CDH and an
      electrode can occur by direct electron transfer (DET) and by mediated electron
      transfer (MET). This characteristic makes CDH an interesting candidate for
      integration in systems such as biosensors and biofuel cells. Moreover, it makes
      CDH an alternative for the reduction of metal ions through DET and MET. In this
      work we have explored the localized deposition of gold on Pd substrates by CDH
      through DET and MET. For this purpose we exploited the advantage of scanning
      electrochemical microscopy (SECM) as a patterning tool. We first demonstrated
      that gold nanoparticles can be formed in homogenous solution. Then we showed that
      Au nanoparticles can also be locally formed and deposited on surfaces through DET
      at low pH and by MET at neutral pH using benzoquinone/hydroquinone as mediator.

PMID- 20821763
TI  - Getting ring-closing metathesis off the bench: reaction-reactor matching
      transforms metathesis efficiency in the assembly of large rings.
AB  - Reported is the first study of the influence of reactor configuration on the
      efficiency of a challenging ring-closing metathesis (RCM) reaction. With the
      intention of increasing the generality of RCM scaleup and reducing its dependence
      on substrate modification, macrocyclization of an unmodified, low effective
      molarity diene was explored using different reactor types, in conjunction with a
      commercial, homogeneous Grubbs catalyst. Optimized performance is compared for a
      conventional batch reactor (BR), a continuous plug-flow reactor (PFR), and a
      continuous stirred-tank reactor (CSTR). In the PFR, maximum conversion is
      achieved most rapidly, but product yields and selectivity are adversely affected
      by co-entrapment of ethylene with the catalyst, substrate, and product in the
      traveling "plug". Use of the CSTR, in which ethylene is efficiently swept out,
      affords an order-of-magnitude increase in total turnover numbers, and reduces the
      required catalyst loadings by 25* relative to the BR (to 0.2 mol %), while
      improving RCM yields and selectivity to quantitative levels. Continuous-flow
      methodologies that support liberation of the ethylene co-product thus show great
      promise for industrial uptake of RCM.

PMID- 20821764
TI  - Imaging the oxidation of ZnS encapsulated in carbon nanotubes.

PMID- 20821765
TI  - A palladium/copper bimetallic catalytic system: dramatic improvement for Suzuki
      Miyaura-type direct C-H arylation of azoles with arylboronic acids.

PMID- 20821766
TI  - Room-temperature deoxygenation of epoxides with CO catalyzed by hydrotalcite
      supported gold nanoparticles in water.

PMID- 20821767
TI  - Synthesis and structures of multifunctionalized helicenes and dehydrohelicenes:
      an efficient route to construct cyan fluorescent molecules.

PMID- 20821769
TI  - Dramatic impact of ppb levels of palladium on the "copper-catalyzed" Sonogashira
      coupling.

PMID- 20821768
TI  - Electronic and optical properties in the solid-state molecular assemblies of
      anion-responsive pyrrole-based pi-conjugated systems.
AB  - On the basis of the chemistry in solution, the solid-state structures and the
      corresponding electronic and optical properties of dipyrrolyldiketone boron
      complexes as pi-conjugated acyclic anion receptors have been investigated. Solid
      state assemblies of the receptors exhibit anion-dependent properties that are in
      sharp contrast to those in the solution state. Anion complexation, along with
      structural differences in the pyrrole subunits such as a benzo-fused pyrrole,
      plays an essential role not only in the formation of the assembled modes but also
      in determining electronic and optical properties, as well as the charge-carrier
      mobilities. In addition, by anion complexation, inclusion of the counter cations
      into the crystals has also been found to be one of the essential factors to
      determine the properties.

PMID- 20821770
TI  - Dendrimer-induced molecular catalysis in water: the example of olefin metathesis.

PMID- 20821771
TI  - Sonoluminescence from OH(C2Sigma+) and OH(A2Sigma+) radicals in water: evidence
      for plasma formation during multibubble cavitation.

PMID- 20821772
TI  - Imaging of self-assembled structures: interpretation of TEM and cryo-TEM images.
AB  - The investigation of solution-borne nanostructures by transmission electron
      microscopy (TEM) is a frequently used analytical method in materials chemistry.
      In many cases, the preparation of the TEM sample involves drying and staining
      steps, and the collection of images leads to the interaction of the specimen with
      the electron beam. Both aspects call for cautious interpretation of the resulting
      electron micrographs. Alternatively, a near-native solvated state can be
      preserved by cryogenic vitrification and subsequent imaging by low-dose cryogenic
      TEM. In this Minireview, we provide a critical analysis of sample preparation,
      and more importantly, of the acquisition and interpretation of electron
      micrographs. This overview should provide a framework for the application of
      (cryo)-TEM as a powerful and reliable tool for the analysis of colloidal and self
      assembled structures with nanoscopic dimensions.

PMID- 20821773
TI  - Strong detrimental effect of a minute enantiomeric impurity of a chiral selector
      on the enantioselectivity factor.

PMID- 20821774
TI  - Telomeres and telomerase: the means to the end (Nobel lecture).

PMID- 20821775
TI  - Efficient synthesis of pyrazoles: oxidative C-C/N-N bond-formation cascade.

PMID- 20821776
TI  - The cis-[Ru(II)(bpy)2(H2O)2]2+ water-oxidation catalyst revisited.

PMID- 20821778
TI  - (In(1-y)Mn(y))MnO3 (1/9<=y<=1/3): unusual perovskites with unusual properties.

PMID- 20821777
TI  - Discrimination between hard metals with soft ligand donor atoms: an on
      fluorescence probe for manganese(II).

PMID- 20821779
TI  - Acceleration of the substitution of silanes with Grignard reagents by using
      either LiCl or YCl3/MeLi.

PMID- 20821780
TI  - Rhodium-catalyzed asymmetric 1,4-addition of aryl alanes to trisubstituted
      enones: binap as an effective ligand in the formation of quaternary
      stereocenters.

PMID- 20821781
TI  - Increasing the Bronsted acidity of flame-derived silica/alumina up to zeolitic
      strength.

PMID- 20821782
TI  - Amphiphilic self-assembly of an n-type nanotube.

PMID- 20821783
TI  - Carboxylic acid catalyzed keto-enol tautomerizations in the gas phase.

PMID- 20821784
TI  - Structural diversity in non-layered hybrid perovskites of the RMCl3 family.

PMID- 20821785
TI  - Photoswitchable supramolecular hydrogels formed by cyclodextrins and azobenzene
      polymers.

PMID- 20821786
TI  - Diastereoselective synthesis of homoallylic alcohols with adjacent tertiary and
      quaternary centers by using functionalized allylic aluminum reagents.

PMID- 20821787
TI  - Stereocontrolled creation of all-carbon quaternary stereocenters by
      organocatalytic conjugate addition of oxindoles to vinyl sulfone.

PMID- 20821788
TI  - 1,2-Azaborine cations.

PMID- 20821790
TI  - Complementary PCAF-coenzyme A mutagenesis: chemoenzymatic synthesis of a novel
      enlarged coenzyme A analogue and evaluation of its biological activity.

PMID- 20821792
TI  - Metal ion modulated torsion angle in a ditopic oligothiophene ligand: toward
      supramolecular control of pi conjugation.
AB  - A pi-conjugated oligomer bearing two 15-crown-5-containing styryl moieties
      connected at the inner beta positions of the terminal thiophene nuclei can adopt
      either a U or a Z shape depending on the structures of its complexes with
      magnesium and barium ions. We show that barium cations lead to the formation of a
      mononuclear complex in solution, which causes the system to fold into the U
      shape. Magnesium ions lead to the same effect at low concentration, but force the
      ligand to adopt the Z-shaped geometry at high concentrations favoring formation
      of a binuclear complex. These geometrical reorganizations in solution are
      accompanied by profound changes in spectroscopic properties, which can be
      rationalized in terms of variations in the extent of electron delocalization
      along the oligothiophene backbone. The effects are analyzed by mass spectrometry
      and (1)H NMR, UV/Vis absorption, and fluorescence spectroscopy in the steady
      state and time-resolved regimes. The experimental results are compared to data
      calculated by using MOPAC2007 with the PM6 Hamiltonian including the COSMO
      solvation model.

PMID- 20821791
TI  - High specificity in protein recognition by hydrogen-bond-surrogate alpha-helices:
      selective inhibition of the p53/MDM2 complex.

PMID- 20821793
TI  - Flowerlike vanadium sesquioxide: solvothermal preparation and electrochemical
      properties.
AB  - A novel 3D hierarchical flowerlike vanadium sesquioxide (V(2)O(3))
      nano/microarchitecture consisting of numerous nanoflakes is prepared via a
      solvothermal approach followed by an appropriate heating treatment. The as
      obtained nanostructured V(2)O(3) flower is characterized by X-ray diffraction
      (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) analysis,
      and transmission electron microscopy (TEM) (or/and high-resolution TEM, HRTEM),
      and it is found that the V(2)O(3) flower is constructed by single-crystalline
      nanoflakes. Furthermore, it is demonstrated that the surface of the flowerlike
      V(2)O(3) material is composed of nanostructured pores, which derive from the
      adsorption/desorption of nitrogen, and that the pore-size distribution depends on
      the unique three-dimensional interconnection between nanoflakes and on their
      intrinsic properties. The electrochemical behavior of the V(2)O(3) flower for
      lithium-ion insertion/extraction in non-aqueous solution as well as the faradaic
      capacitance for pesudocapacitors in a neutral aqueous solution are also
      investigated. A reversible discharge capacity as high as 325 mA h g(-1) is
      obtained at a current density of 0.02 A g(-1) from a LiClO(4)/EC:DEC electrolyte
      solution (i.e. LiClO(4) in ethyl carbonate and diethyl carbonate). When used as
      the cathode material of pesudocapacitors in Li(2)SO(4), the flowerlike oxide
      displayed a very high initial capacitance of 218 F g(-1) at a current density of
      0.05 A g(-1). We believe that the good performance of the flowerlike V(2)O(3)
      electrode is most probably due to its unique 3D hierarchical
      nano/microarchitecture, which shows that the electrochemical properties of a
      cathodic material do not only depend on the oxidation state of that material but
      also-to a large extent-on its crystalline structure and morphology. The
      aforementioned properties suggest that the present V(2)O(3) flower materials may
      have a great potential to be employed as electrode materials in rechargeable
      lithium batteries and pesudocapacitors.

PMID- 20821794
TI  - Conservation of orbital symmetry can be circumvented in mechanically induced
      reactions.
AB  - In first-principles molecular dynamics simulations of the mechanically induced
      ring-opening of substituted benzocyclobutene we observe both con- and disrotatory
      ring-opening reactions. We show that this finding does not contradict the
      fundamental principle that the orbitals develop continuously in time. However, it
      constitutes an exception from the principle of the conservation of orbital
      symmetry and thus is indeed an exception from the Woodward-Hoffmann rules. In
      contrast, the ring-opening of unsubstituted cyclobutene proceeds in a conrotatory
      fashion. This shows that the breaking of the Woodward-Hoffmann rules is
      significantly facilitated by the substituents.

PMID- 20821795
TI  - MRI thermometry based on encapsulated hyperpolarized xenon.
AB  - A new approach to MRI thermometry using encapsulated hyperpolarized xenon is
      demonstrated. The method is based on the temperature dependent chemical shift of
      hyperpolarized xenon in a cryptophane-A cage. This shift is linear with a slope
      of 0.29 ppm  degrees C(-1) which is perceptibly higher than the shift of the
      proton resonance frequency of water (ca. 0.01 ppm  degrees C(-1)) that is
      currently used for MRI thermometry. Using spectroscopic imaging techniques, we
      collected temperature maps of a phantom sample that could discriminate by direct
      NMR detection between temperature differences of 0.1  degrees C at a sensor
      concentration of 150 MUM. Alternatively, the xenon-in-cage chemical shift was
      determined by indirect detection using saturation transfer techniques (Hyper
      CEST) that allow detection of nanomolar agent concentrations. Thermometry based
      on hyperpolarized xenon sensors improves the accuracy of currently available MRI
      thermometry methods, potentially giving rise to biomedical applications of
      biosensors functionalized for binding to specific target molecules.

PMID- 20821796
TI  - Drugs for hepatitis C: unlocking a new mechanism of action.

PMID- 20821797
TI  - Combat experience and the acquired capability for suicide.
AB  - Rising suicide rates are an increasing concern among military personnel. The
      interpersonal-psychological theory of suicide proposes that three necessary
      factors are needed to die by suicide: feelings that one does not belong with
      other people, feelings that one is a burden on others or society, and an acquired
      capability to overcome the fear and pain associated with suicide. The current
      study tests the theory's proposal that acquired capability may be particularly
      influenced by military experience, because combat exposure may cause habituation
      to fear of painful experiences such as suicide. Utilizing clinical and
      nonclinical samples of military personnel deployed to Iraq, results of the
      current study indicate that a greater range of combat experiences predicts
      acquired capability above and beyond depression and post-traumatic stress
      disorder symptoms, previous suicidality, and other common risk factors for
      suicide. Combat experiences did not, however, predict perceived burdensomeness or
      thwarted belongingness. The authors discuss how combat experiences might serve as
      a mechanism for elevating suicide risk and implications for clinical
      interventions and suicide prevention efforts.

PMID- 20821798
TI  - The contribution of precipitants to depression onset, diagnostic sub-type, and
      treatment paradigm: a "mix and match" model.

PMID- 20821800
TI  - Executive control of attention in individuals with contamination-related
      obsessive-compulsive symptoms.
AB  - BACKGROUND: In this study, we examined executive control of attention in
      individuals with contamination-related obsessive-compulsive (OC) symptoms using a
      modified version of the Eriksen flanker task. The task indexes one's ability to
      resolve attentional conflict between different responses and to ignore task
      distracters. METHODS: For this study, we modified the original flanker task using
      affective words to examine the effect of threat-relevant stimuli on executive
      control of attention. Consistent with research on information processing biases
      in individuals with OC symptoms, we hypothesized that the flanker interference
      effect (i.e., difference in response latencies between incongruent and congruent
      flanker trials) will be greater for threat-related flankers in individuals with
      OC symptoms (n=32), relative to a control group (n=36). RESULTS: Results of our
      study were consistent with our hypothesis: The interference effect for threat
      flankers was greater in individuals with OC symptoms than in those low in
      symptoms. Moreover, there was no differential interference effect in the low and
      high symptom groups for neutral flankers. CONCLUSIONS: These findings suggest
      that the presence of threat-relevant distracters disrupts executive control of
      attention in individuals with contamination-related OC symptoms. These results
      are consistent with extant research on attentional biases in individuals with
      clinical and subclinical symptoms of OCD.

PMID- 20821801
TI  - Deconstructing acrophobia: physiological and psychological precursors to
      developing a fear of heights.
AB  - BACKGROUND: Acrophobia is one of the most prevalent phobias, affecting as many as
      1 in 20 individuals. Of course, heights often evoke fear in the general
      population too, and this suggests that acrophobia might actually represent the
      hypersensitive manifestation of an everyday, rational fear. In this study, we
      assessed the role of sensory and cognitive variables in acrophobia. METHODS:
      Forty-five participants (Mean age 25.07 years, 71% female) were assessed using a
      booklet with self-reports as well as several behavioral measures. The data
      analysis consisted in multivariate linear regression using fear of heights as the
      outcome variable. RESULTS: The regression analyses found that visual field
      dependence (measured with the rod and frame test), postural control (measured
      with the Sharpened Romberg Test), space and motion discomfort (measured with the
      Situational Characteristics Questionnaire), and bodily symptoms (measured with
      the Bodily Sensation Questionnaire) all serve as strong predictors for fear of
      heights (Adjusted r(2)=.697, P<.0001). Trait anxiety (measured with the State
      Trait Anxiety Inventory Form Y-2) was not related with fear of heights,
      suggesting that this higher order vulnerability factor is not necessary for
      explaining this particular specific phobia in a large number of individuals.
      CONCLUSION: The findings reveal that fear of heights is an expression of a
      largely sensory phenomena, which can produce strong feelings of discomfort and
      fear in the otherwise calm individuals. We propose a theory that embraces all
      these factors and provides new insight into the aetiology and treatment of this
      prevalent and debilitating fear.

PMID- 20821799
TI  - Depression and obesity: do shared genes explain the relationship?
AB  - BACKGROUND: Studies have found a modest association between depression and
      obesity, especially in women. Given the substantial genetic contribution to both
      depression and obesity, we sought to determine whether shared genetic influences
      are responsible for the association between these two conditions. METHODS: Data
      were obtained from 712 monozygotic and 281 dizygotic female twin pairs who are
      members of the community-based University of Washington Twin Registry. The
      presence of depression was determined by self-report of doctor-diagnosed
      depression. Obesity was defined as body mass index of > or =30 kg/m(2), based on
      self-reported height and weight. Generalized estimating regression models were
      used to assess the age-adjusted association between depression and obesity.
      Univariate and bivariate structural equation models estimated the components of
      variance attributable to genetic and environmental influences. RESULTS: We found
      a modest phenotypic association between depression and obesity (odds ratio=1.6,
      95% confidence interval=1.2-2.1). Additive genetic effects contributed
      substantially to depression (57%) and obesity (81%). The best-fitting bivariate
      model indicated that 12% of the genetic component of depression is shared with
      obesity. CONCLUSIONS: The association between depression and obesity in women may
      be in part due to shared genetic risk for both conditions. Future studies should
      examine the genetic, environmental, social, and cultural mechanisms underlying
      the relationship between this association.

PMID- 20821802
TI  - The acquired capability for suicide: a comparison of suicide attempters, suicide
      ideators, and non-suicidal controls.
AB  - BACKGROUND: The Interpersonal Theory of Suicide states that to make a serious or
      lethal suicide attempt, a person must experience reductions in fear and pain
      sensitivity sufficient to overcome self preservation reflexes (i.e., the acquired
      capability for suicide). The purpose of this study was to examine the
      fearlessness component of the acquired capability for suicide using self-report
      assessment instruments and an objective measure of aversion (the affectively
      modulated startle reflex task). METHODS: Depressed suicide ideators (n=15),
      depressed suicide attempters (n=15), and a group of control participants (n=14)
      were compared on their self-report of acquired capability and painful and
      provocative life events, and completed the affectively modulated startle reflex
      task. This task compared electromyography recordings of participants' eye-blink
      response to a startle probe while viewing pictures of varying hedonic valence
      (neutral, positive, negative, and suicide-related). RESULTS: Suicide attempters
      reported the highest levels of fearlessness and pain insensitivity and a greater
      history of painful and provocative life events. Although no group differences
      were found on the psychophysiology data, participants reacted to suicide-related
      images with less aversion compared to neutral images with no differences between
      suicide-related and positive images. CONCLUSIONS: Self-reported fearlessness and
      pain insensitivity can differentiate suicide attempters and suicide ideators.
      Results suggest that one's self-perception (i.e., cognitions regarding fear and
      pain tolerance) are more functionally related to suicide attempts than
      psychophysiological reactivity to suicide-related stimuli.

PMID- 20821803
TI  - Psychosocial interventions as part of breast cancer rehabilitation programs?
      Results from a systematic review.
AB  - OBJECTIVE: This systematic review aimed to determine the effectiveness of
      psychoeducation, cognitive behavioural therapy (CBT) and social support
      interventions used in the rehabilitation of breast cancer (BC) patients. METHODS:
      We conducted a systematic literature search to identify randomised controlled
      trials of female BC patients who underwent different psychosocial interventions
      during or after primary cancer treatment. The methodological quality of all
      studies was independently assessed by two reviewers. Studies with low quality,
      less than 20 participants in each group, patients with metastatic cancer, data
      not presented separately for BC and studies that included other cancer types were
      excluded. RESULTS: Among 9617 identified studies, only 18 RCTs published between
      1999 and 2008, including 3272 patients were finally included in this systematic
      evaluation. Outcome measures were categorised into quality of life (QoL),
      fatigue, mood, health behaviour and social function. Six trials examined
      psychoeducation had inconsistent results, both during and after the primary
      treatment. Seven trials examined the effect of CBT, four of which given after
      primary treatment (range 6-12 weeks) demonstrated improvements in QoL; the other
      three CBT studies given during primary treatment (range 9-20 weeks) had
      inconsistencies. Five studies addressed social support and showed no conclusive
      impacts of this intervention. CONCLUSIONS: Limited documentation exists on the
      efficacy of psychosocial rehabilitation interventions among BC patients. However,
      we found that patients might have QoL benefits from CBT given after primary BC
      treatment. More documentation is needed regarding the effects of CBT during
      primary treatment and the effects of psychoeducation and social support.

PMID- 20821804
TI  - Annexin A1 attenuates EMT and metastatic potential in breast cancer.
AB  - Metastasis is the major cause of carcinoma-induced death, but mechanisms involved
      are poorly understood. Metastasis crucially involves epithelial-to-mesenchymal
      transition (EMT), causing loss of epithelial polarity. Here we identify Annexin
      A1 (AnxA1), a protein with important functions in intracellular vesicle
      trafficking, as an efficient suppressor of EMT and metastasis in breast cancer.
      AnxA1 levels were strongly reduced in EMT of mammary epithelial cells, in
      metastatic murine and human cell lines and in metastatic mouse and human
      carcinomas. RNAi-mediated AnxA1 knockdown cooperated with oncogenic Ras to induce
      TGFbeta-independent EMT and metastasis in non-metastatic cells. Strikingly,
      forced AnxA1 expression in metastatic mouse and human mammary carcinoma cells
      reversed EMT and abolished metastasis. AnxA1 knockdown stimulated multiple
      signalling pathways but only Tyk2/Stat3 and Erk1/2 signalling were essential for
      EMT.

PMID- 20821805
TI  - Development of selected reaction monitoring-MS methodology to measure peptide
      biomarkers in prostate cancer.
AB  - Prostate cancer is a leading cause of cancer-related death. The current modality
      of diagnosis, the measurement of serum PSA, not only suffers from lack of
      specificity, but does not distinguish clinical cases in which current treatment
      measures would be most successful, i.e. aggressive, life-threatening tumors. A
      multiplexed MS methodology, selected reaction monitoring-MS/MS coupled with
      stable isotope dilution (SID), was developed and tested in both cells lines and
      clinical tissue samples. Standard curves were generated for two peptides
      representing PSA and one peptide from each of two additional orthogonally
      validated biomarkers, AMACR and EZH2. The standard curves show high
      reproducibility, sensitivity, and good linearity. All four peptides were then
      measured in six clinically relevant cell lines and are in agreement with the
      biochemical characteristics of each individual cell line. The SID selected
      reaction monitoring-MS/MS methodology was then transferred to tissue samples, in
      which the assay shows potential to differentiate benign disease from localized
      cancer and localized cancer from aggressive metastatic disease. These results
      establish the preliminary development of a rational targeted MS platform that
      strives to bridge the gap between discovery and validation of biomarkers for the
      detection of prostate cancer.

PMID- 20821806
TI  - LTQ-iQuant: A freely available software pipeline for automated and accurate
      protein quantification of isobaric tagged peptide data from LTQ instruments.
AB  - Pulsed Q dissociation enables combining LTQ ion trap instruments with isobaric
      peptide tagging. Unfortunately, this combination lacks a technique which
      accurately reports protein abundance ratios and is implemented in a freely
      available, flexible software pipeline. We developed and implemented a technique
      assigning collective reporter ion intensity-based weights to each peptide
      abundance ratio and calculating a protein's weighted average abundance ratio and
      p-value. Using an iTRAQ-labeled standard mixture, we compared our technique's
      performance to the commercial software MASCOT, finding that it performed better
      than MASCOT's nonweighted averaging and median peptide ratio techniques, and
      equal to its weighted averaging technique. We also compared performance of the
      LTQ-Orbitrap plus our technique to 4800 MALDI TOF/TOF plus Protein Pilot, by
      analyzing an iTRAQ-labeled stem cell lysate. We found highly correlated protein
      abundance ratios, indicating that the LTQ-Orbitrap plus our technique yields
      results comparable to the current standard. We implemented our technique in a
      freely available, automated software pipeline, called LTQ-iQuant, which is mzXML
      compatible; supports iTRAQ 4-plex and 8-plex LTQ data; and can be modified for
      and have weights trained to a user's LTQ and other isobaric peptide tagging
      methods. LTQ-iQuant should make LTQ instruments and isobaric peptide tagging
      accessible to more proteomic researchers.

PMID- 20821807
TI  - Contribution of microwave accelerated distillation in the extraction of the
      essential oil of Zygophyllum album L.
AB  - INTRODUCTION: The aerial parts of Zygophyllum album L. are used in folk medicine
      as an antidiabetic agent and as a drug active against several pathologies. In
      this work we present the chemical composition of Algerian essential oils obtained
      by microwave accelerated distillation (MAD) extraction, a solventless method
      assisted by microwave. OBJECTIVE: Under the same analytical conditions and using
      GC-FID and GC-MS, the chemical composition of the essential oil of Zygophyllum
      album L. extracted by MAD was compared with that achieved using hydrodistillation
      (HD). METHODOLOGY: The extracted compounds were hydrosoluble, and they were
      removed from the aqueous solution by a liquid extraction with an organic solvent.
      RESULTS: Employing MAD (100 degrees C, 30  min), the essential oil contained
      mainly oxygenated monoterpenes with major constituents: carvone and alpha
      terpineol. However, most of the compounds present in the hydrodistilled volatile
      fraction were not terpene species, with beta-damascenone as a major constituent.
      CONCLUSION: The MAD method appears to be more efficient than HD: after 30  min
      extraction time, the obtained yields (i.e. 0.002%) were comparable to those
      provided by HD after 3  h extraction. MAD seems to be more convenient since the
      volatile fraction is richer in oxygenated monoterpenes, species that are
      recognised for their olfactory value and their contribution to the fragrance of
      the essential oil.

PMID- 20821808
TI  - Synchronous fluorescence determination of phytic acid in foodstuffs and urine
      based on replacement reaction.
AB  - INTRODUCTION: Phytic acid is a ubiquitous and abundant natural component in many
      plant seeds, fruits and vegetables. Its biological and pharmaceutical functions
      are still controversial. The examination on the level of phytic acid in
      foodstuffs and urine can provide valuable information for its dietary intake and
      metabolism. OBJECTIVE: To develop a sensitive and reliable synchronous
      fluorescence protocol for determination of phytic acid in selected foodstuffs and
      human urine. METHODOLOGY: Phytic acid efficiently catches Cu2+ ion in previously
      prepared Cu(II) -2,2'-bipyridine complex in aqueous solution, releasing the
      fluorescent 2,2'-bipyridine molecule and recovering synchronous fluorescence. The
      recovered fluorescence is proportional to the added phytic acid, by which the
      levels of phytic acid in the selected foodstuffs and human urine are quantified.
      RESULTS: A calibration curve with a regression equation of I(f) = 37.745 +
      39.245c (R2 > 0.9988) showed good linearity over the range 0.18-17.50 mg/L phytic
      acid. The relative standard deviation at 95% confidence degree was less than
      2.04% (n = 5), indicating that the procedures are reproducible. The detection and
      quantification limit of phytic acid were estimated to be 0.12 and 0.18 mg/L,
      respectively. By the proposed method, phytic acid in the selected foodstuffs and
      urine was determined to be 3.25-16.76 and 0.43-1.21 mg/L with recoveries of 96.8%
      105.6% and 95.1%-104.2%, respectively. The results are in good agreement with
      those obtained by the reported HPLC technique. CONCLUSION: The developed method
      is sensitive, reliable and economical, which permits its practical application in
      quantitative analyses of trace phytic acid in foodstuffs and urine.

PMID- 20821809
TI  - Determination of Co(II) in plant tissue by microwave digestion and ion
      chromatography coupled with luminol/perborate or luminol/percarbonate
      chemiluminescence detection.
AB  - INTRODUCTION: The cobalt is an essential element for leguminous plants but may be
      harmful for other species; for that reason determination of Co(II) is very
      important for the management of polluted areas and for discover plants with
      capacity for the hyperaccumulation of heavy metals, which has produced a growing
      necessity of fast, sensitive and selective analytical techniques. OBJECTIVE: To
      develop an analytical procedure for the determination of cobalt in plant tissue
      by coupling the ionic chromatography to the luminol-based chemiluminescence
      detection. METHODOLOGY: The sample was digested in a mixture of concentrated
      nitric acid and hydrogen peroxide, using an microwave oven to dissolve the
      Co(II). The solution containing Co(II) ions was injected to an ionic
      chromatograph using oxalic acid as the eluent. The detection was based on the
      catalytic effect of Co(II) on the luminol chemiluminescence using perborate or
      percarbonate as oxidants. Experimental variables, such as concentrations, pH,
      flow rates and acid digestion conditions were optimised. RESULTS: Well-resolved
      chromatographic peaks were obtained. The height and area showed linear
      dependences with the Co(II) concentration, which were used to quantify the heavy
      metal, with recoveries up to 95%. The microwave irradiation (60  s) was
      sufficient for the complete mineralisation of 200  mg of sample, employing 2  mL
      of the acid mixture. The method was free from the interferences, requiring less
      than 12 minutes to complete the analysis. CONCLUSION: The method was simple and
      rapid for the determination of cobalt in plant tissue with detection limits
      comparable to those obtained with more sophisticated and expensive analytical
      equipment.

PMID- 20821810
TI  - Molecular biology, phytochemistry and bioactivity of three endemic Aloe species
      from Mauritius and Reunion Islands.
AB  - INTRODUCTION: Aloe tormentorii, A. purpurea and A. macra are used as multipurpose
      folk medicines in Reunion and Mauritius Islands and are mistaken for the
      introduced Aloe vera. OBJECTIVE: To compare the phytochemical, antimicrobial and
      DNA profiles of Aloe endemic to Mauritius and Reunion with the profiles of A.
      vera. Methodology - Leaf extracts of these Aloe species were analysed using
      standard phytochemical screening techniques, TLC and by HPLC. These extracts were
      also assayed for antimicrobial activity using microdilution techniques. Genetic
      diversity was studied using RAPD markers. RESULTS: Phytochemical and
      antimicrobial assays and RAPD analysis showed that Mascarene Aloe species were
      very different from A. vera. CONCLUSION: This study is the first report
      highlighting the differences between Aloe sp.p from Mascarene and Aloe vera at
      the metabolic and genomic level.

PMID- 20821811
TI  - Speciation analysis, bioavailability and risk assessment of trace metals in
      herbal decoctions using a combined technique of in Vitro digestion and
      biomembrane filtration as sample pretreatment method.
AB  - Sample preparation is the first crucial step in the speciation analysis,
      bioavailability and risk assessment of trace metals in plant samples such as herb
      and vegetables. Two bionic technologies titled 'in vitro digestion' and
      'extraction with biomembrane' were developed for pre-treatment of herbal
      decoction. The decoctions of Aconiteum carmichaeli and Paeonia lactiflora were
      digested at body temperature, at the acidity of the stomach or intestine and with
      inorganic and organic materials (digestive enzymes were included for whole-bionic
      and excluded for semi-bionic) found in the stomach or intestine. Being similar to
      the biomembrane between the gastrointestinal tract and blood vessels, monolayer
      liposome was used as a biomembrane model. Affinity-monolayer liposome metals and
      water-soluble metals were used for speciation analysis and bioavailability
      assessment of copper and zinc in herbal decoction. In the decoction of Aconiteum
      carmichaeli and Paeonia lactiflora, Zn was mainly absorbed in the intestine and
      Cu was mainly absorbed by both stomach and intestine. The safe dosage for males
      and females is below 257.1 g/day Aconiteum carmichaeli and 529.4 g/day Paeonia
      lactiflora.

PMID- 20821812
TI  - Development of an LC-MS method for simultaneous quantitation of amentoflavone and
      biapigenin, the minor and major biflavones from Hypericum perforatum L., in human
      plasma and its application to real blood.
AB  - INTRODUCTION: Biflavones of Hypericum perforatum L. are bioactive compounds used
      in the treatment of inflammation and depression. Determination of amentoflavone
      and biapigenin from blood is challenging owing to their similar structures and
      low concentrations. OBJECTIVE: To develop a rapid, sensitive and accurate method
      based on liquid-phase extraction followed by high-performance liquid
      chromatography and electrospray ionisation mass spectrometry (HPLC-ESI-MS) for
      quantification of biflavones in human plasma. METHODOLOGY: After extraction from
      blood, the analytes were subjected to HPLC with an XTerra(r) MS C(18) column and
      a binary mobile phase consisting of 2% formic acid in water and acetonitrile
      under isocratic elution conditions, with ESI-MS detection in the negative ion
      mode and multiple reaction monitoring (MRM). RESULTS: Both calibration curves
      showed good linearity within the concentration range 1-500  ng/mL. Limits of
      detection (S/N = 3) were 0.1  ng for pure substances and the limits of
      quantitation (S/N = 5) were 1.0  ng/mL from analyte-spiked serum. The grand mean
      recovery was 90% from several subsamples of each biflavone. The imprecision (RSD)
      of peak areas was between 5% (intraday) and 10% (interday) for high
      concentrations (250  ng/mL) and between 10% (intraday) and 15% (interday) for low
      concentrations (1  ng/mL). Inaccuracy of the mean was less than 20% at the lower
      limit of quantitation. CONCLUSION: The developed and validated method for
      determination of biflavones from human plasma was effectively applied to
      pharmacokinetic studies of 13 probands and preliminary results indicate biphasic
      concentration-time curves.

PMID- 20821813
TI  - Validated TLC method for simultaneous quantitation of kutkoside and picroside-I
      from Kutki extract.
AB  - INTRODUCTION: The two iridoid glycosides kutkoside and picroside-I are the active
      hepatoprotective principles of Picrorhiza kurroa Royle ex Benth
      (Scrophulariaceae), commonly known as Kutki. Quantitation of these
      phytoconstituents is important for the routine quality control of Kutki extract.
      OBJECTIVE: To develop and validate a simple, precise and rapid thin-layer
      chromatography (TLC) method for the simultaneous quantitation of kutkoside and
      picroside-I in Kutki extract. METHODOLOGY: The analysis was performed on a TLC
      precoated silica gel 60 F(254) plate with ethyl acetate:methanol:glacial acetic
      acid:formic acid (25:5:1:1, v/v/v/v) as mobile phase. Densitometric evaluation of
      kutkoside and picroside-I was carried out at 265  nm and the mobile phase showed
      good resolution with R(f) values 0.42 +/- 0.03 and 0.61 +/- 0.03 for kutkoside
      and picroside-I, respectively. The method was validated in terms of specificity,
      linearity, accuracy and precision. RESULTS: The content of kutkoside and
      picroside-I was found to be 2.18 and 1.90%, respectively, and was comparable with
      those obtained by HPLC. The linearity was found to be in the range of 80-480 
      ng/spot for both kutkoside and picroside-I. The average recovery values were
      found to be 96.5 and 96.0% for kutkoside and picroside-I, respectively.
      CONCLUSION: The developed method was found to be relatively simple, precise and
      reproducible for the simultaneous quantitation of kutkoside and picroside-I. The
      method does not employ any derivatisation procedure and can be used as a quality
      control tool for the routine analysis of commercial Kutki extracts.

PMID- 20821814
TI  - Empathy or objectivity: The forensic examiner's dilemma?
AB  - Examiners are ethically bound to manage personal biases that may infect their
      expert opinions. Empathy-related issues that lead to bias in forensic assessment
      of adjudicative competence arise in evaluation interactions with defendants
      (therapeutic empathy) and from examiners' personal views of issues that these
      assessments address (empathy-bias). This article first summarizes flexible
      adjudicative competence legal standards that invite bias by forensic experts.
      Then, after reviewing the therapeutic empathy issue, the article examines empathy
      bias and its effects on the development of expert opinions. The authors assert
      that, properly managed, the often assumed dilemma between empathy and objectivity
      is a false one. Using case law, research psychology, and professional guidelines,
      the authors first emphasize that examiners must actively generate plausible
      alternative explanations of evaluation data as they form their opinions, not
      afterwards. Then the authors present a practical model to help experts develop
      opinions that best explain the data while minimizing empathy-bias.

PMID- 20821815
TI  - Moxibustion for treating pain: a systematic review.
AB  - The objective of this study was to assess the evidence for or against the
      effectiveness of moxibustion as a treatment option for pain. Fourteen electronic
      databases were searched. Randomized clinical trials (RCTs) testing moxibustion in
      human patients with pain of any type were considered. Trials using direct or
      indirect moxibustion were included. Studies comparing moxibustion with other
      treatments of unproven effectiveness, studies testing moxibustion together with
      other treatments of unproven efficacy and trials where pain was not a central
      symptom of the condition were all excluded. The selection of studies, data
      extraction, and validation were performed independently by two reviewers. Four
      RCTs met all the inclusion criteria. Others were of poor methodological quality.
      Two RCTs suggested significant pain reductions for indirect moxibustion in
      osteoarthritis as compared with drug therapy (n = 200, RR, 1.11; 95% CI of 1.02
      to 1.21, p = 0.02, heterogeneity: chi2 = 1.03, p = 0.31, I2 = 3%). The other two
      RCTs suggested positive effects of indirect or direct moxibustion on pain in
      scleroma or herpes zoster compared to drug therapy, respectively. We conclude
      that few RCTs are available that test the effectiveness of moxibustion in the
      management of pain, and most of the existing trials have a high risk of bias.
      Therefore, more rigorous studies are required before the effectiveness of
      moxibustion for the treatment of pain can be determined.

PMID- 20821816
TI  - The acute effects of acupuncture upon autonomic balance in healthy subjects.
AB  - Restoration of the sympathovagal (S/V) balance, involving a lowering of
      sympathetic and/or an augmentation of vagal modulation or a combination of both
      is associated with improvements in cardiovascular morbidity and mortality. To
      determine whether acupuncture exerts a favorable influence upon resting blood
      pressure and sympathovagal balance, a single-blind cross-over investigation was
      used to study the acute effects of acupuncture on S/V balance in normal healthy
      subjects. The ANOVA revealed a significant lowering of the sympathovagal balance
      (LF:HF) during rest for the acupuncture treatment from pre (4 +/- 2 nu) to post
      (2.2 +/- 1.8 nu)(p < 0.05). No such change was seen during sham treatment. The
      ANOVA revealed significant differences in systolic blood pressures during rest
      (114 +/- 4 vs. 108 +/- 3 mmHg) for the acupuncture treatment (p < 0.05). No
      significance was found during the sham treatment. The ANOVA failed to reveal any
      significant improvements in sympathovagal balance during the sustained isometric
      contraction. The clinical significance of these findings appears to suggest that
      acupuncture treatment might be beneficial in lowering blood pressure at rest.
      Furthermore, the lowering of the blood pressure might be in part due to a
      lowering of the sympathovagal balance. These findings are of importance since
      acupuncture treatments are non-pharmacological and have no known detrimental side
      effects. This investigation employed healthy volunteers, yet acupuncture has been
      found to have more potent effects in animal models of hypertension and or in the
      presence of an autonomic imbalance.

PMID- 20821817
TI  - The therapeutic effects of acupuncture on patients with chronic neck myofascial
      pain syndrome: a single-blind randomized controlled trial.
AB  - Chronic neck myofascial pain syndrome (MPS) is a common disorder seen in clinics.
      There is no gold standard method to treat myofascial pain. We investigated the
      effects of acupuncture on patients with chronic neck MPS by a single-blind
      randomized controlled trial. A total of 35 patients were randomly allocated to an
      acupuncture group (AG) or a sham acupuncture group (SG). Each subject received
      acupuncture treatment twice per week for three consecutive weeks. The primary
      outcome measure was quality of life as assessed with Short Form-36, and secondary
      outcome measures were neck range of motion (ROM), motion-related pain, and Short
      Form McGill Pain Questionnaire (SF-MPQ), as determined by a blinded investigator.
      The clinical assessments were made before treatment (BT) and after six
      acupuncture treatments (AT), as well as four weeks (F1) and 12 weeks (F2) after
      the end of the treatment. A total of 34 patients completed the trial. The results
      indicated that there is no significant difference in the ROM, motion-related
      pain, and SF-MPQ scores between AG and SG at AT, F1 and F2 (all p > 0.05).
      However, AG has greater improvement in physical functioning and role emotional of
      Short Form-36 quality of life at F2. The results indicate that acupuncture may be
      used to improve the quality of life in patients with chronic neck MPS.

PMID- 20821818
TI  - Clinical observations on laser acupuncture in simple obesity therapy.
AB  - A previous study has shown that laser acupuncture is a useful healing method for
      the treatment of visceral postmenopausal obesity in combination with a low
      calorie diet. We observe and evaluate the therapeutic effect of laser acupuncture
      in subjects of simple obesity with a non-restrictive diet protocol. Subjects
      included 73 women and 22 men with simple obesity and body mass indices > or = 27
      kg/m2. Daily energy intake recommendations for obese females and males were
      1620.0 and 1894.2 kcal in average, respectively. The gallium aluminum arsenide
      Handylaser Trion was used to apply 0.25 J of energy to each of the following
      acupuncture points three times per week for four consecutive weeks: Stomach,
      Hunger, ST25, ST28, ST40, SP15, and CV9. The subjects' body weights and body mass
      indices were recorded before treatment, and four weeks after treatment, and the
      percent reduction in each parameter was calculated. Statistically significant
      reductions in body weight and body mass index were detected after four weeks of
      treatment. The mean reduction and mean percent reduction in body weight were 3.17
      kg and 3.80% (p < 0.0001), respectively. The corresponding values for the body
      mass index were 1.22 kg/m2 and 3.78% (p < 0.0001), respectively. We concluded
      that laser acupuncture was found to exert a therapeutic effect on simple obesity
      by reducing both body weight and body mass index. Moreover, subjects showed good
      compliance with this comfortable and non-restrictive diet protocol.

PMID- 20821819
TI  - Response properties of nucleus reticularis lateralis neurons after
      electroacupuncture stimulation in rats.
AB  - A descending inhibitory mechanism from the periaqueductal gray (PAG) to the
      spinal cord through the nucleus raphe magnus (NRM) is strongly involved in
      endogenous analgesic system produced by acupuncture stimulation. In addition to
      the PAG to NRM system which descends in the medial pathway of the brain stem, the
      nucleus reticularis lateralis (NRL) situated in the lateral part of the brain
      stem is reported to play an important role in modulating centrifugal
      antinociceptive action. In the present study, to clarify the role of NRL in
      acupuncture analgesia, we investigated the response properties of NRL neurons to
      acupuncture stimulation. The majority of NRM-projecting NRL neurons were
      inhibited by electroacupuncture stimulation. This effect was antagonized by
      ionophoretic application of naloxone, indicating that endogenous opioids act
      directly onto these NRL neurons. By contrast, about half of spinal projecting NRL
      neurons were excited by electroacupuncture stimulation, suggesting that part of
      the NRL neurons may modulate pain transmission directly at the spinal level.

PMID- 20821821
TI  - Pharmacokinetics of laetispicine and its brain distribution in rats.
AB  - Laetispicine, which is a novel amide alkaloid isolated from the stem of Piper
      laetispicum, has been proven to possess antidepressant and antinociceptive
      effects. This study examined the pharmacokinetic characteristics of laetispicine
      in plasma and brain distribution in rats by a simple sensitive HPLC-UV method.
      The separation was performed on a reverse-phase ODS column (250 mm x 4.6 mm,
      i.d., 5 microm) with a mobile phase composed of acetonitrile-water (75:25, v/v)
      as the mobile phase at a flow rate of 1.0 ml/min with UV detection at 259 nm. The
      calibration curve of laetispicine in rat plasma showed excellent linear behavior
      between 0.005-5.0 microg/ml (r2 = 0.9992), and between 0.02-0.5 microg/ml (r2 =
      0.9952) in rat brain samples. The lower limit of quantification (LLOQ) was found
      to be 0.005 microg/ml in rat plasma and 0.02 microg/ml in rat brain samples. This
      HPLC assay was a precise and reliable method for the analysis of laetispicine in
      pharmacokinetic studies. Laetispicine was rapidly and extensively transported
      across the blood-brain barrier (BBB) and distributed into different brain
      regions.

PMID- 20821820
TI  - Hepatoprotection by freshwater clam extract against CCl4-induced hepatic damage
      in rats.
AB  - Freshwater clam is traditionally used as a food and has been mentioned in ancient
      books to have a hepatoprotective effect. The hepatoprotective effect of
      freshwater clam extract was evaluated in the model of chronic hepatic fibrosis
      induced by carbon tetrachloride (CCl4). Male Sprague-Dawley rats were orally
      treated with freshwater clam extract (0.3, 0.6 and 1.5 g/kg of bw) or silymarin
      (0.2 g/kg of bw) along with the administration of CCl4 (0.5 ml/rat, 20% CCl4 in
      olive oil) for eight consecutive weeks. Blood samples were collected for assaying
      serum biochemical parameters. The livers were excised for evaluating peroxidation
      products and antioxidant substances, as well as the activities of antioxidant
      enzymes. Pathological histology was also performed. The data showed that
      supplementation of freshwater clam extract (0.6 g/kg bw) significantly reduced
      the serum levels of alanine aminotransferase and aspartate aminotransferase in
      rats treated with CCl4, and also decreased the thiobarbituric acid reactive
      substances, hydroxyproline and excessive inflammation in the livers of CCl4
      treated rats. Histopathological analysis of the liver showed that freshwater clam
      extract (0.6 g/kg bw) markedly reduced the injury score of the fibrosis induced
      by CCl4 in rats. The data suggest that oral administration with freshwater clam
      extract might provide a novel and alternative approach for treating chronic liver
      failure.

PMID- 20821822
TI  - Pinus massoniana bark extract protects against oxidative damage in L-02 hepatic
      cells and mice.
AB  - The hepatoprotective activity of Pinus massoniana bark extract (PMBE) against
      hydrogen peroxide (H2O2)-induced damage in normal human liver L-02 cells and
      carbon tetrachloride (CCl4)-induced acute hepatotoxicity in mice was
      investigated. The L-02 cells were pre-treated with PMBE for 24 hours prior to
      exposure to 0.5 mM H2O2 for 3 or 24 hours. The cell viability, level of
      malondialdehyde (MDA) and glutathione (GSH), and the catalase (CAT) activity were
      evaluated. For in vivo experiments, mice were divided into groups and PMBE
      administered orally, after which each group was assigned a further treatment.
      Histopathological examination, the serum levels of alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and GSH, the
      liver tissue levels of MDA and GSH, the activities of CAT and glutathione
      peroxidase (GSH-Px), were evaluated. PMBE treatment decreased the level of MDA
      and increased the cell viability, GSH content and CAT activity in H2O2 treated L
      02 cells treated for 3 hours. PMBE obviously decreased serum ALT, AST, ALP, and
      liver tissue MDA, while increasing serum GSH, and liver tissue CAT and GSH-Px
      activities. In conclusion, PMBE treatment prevents H2O2 and CCl4-induced liver
      damage, and therefore could have a potential clinical usage.

PMID- 20821823
TI  - Bee venom inhibits hepatic fibrosis through suppression of pro-fibrogenic
      cytokine expression.
AB  - Bee venom (BV) has a long tradition of use for the control of pain and
      inflammation in various chronic diseases. Carbon tetrachloride (CCl4) is known to
      induce hepatotoxicity after being metabolized to the highly reactive
      trichloromethyl free radical and its peroxy radical. The purpose of the current
      study was to examine whether BV regulates the pro-inflammation and fibrosis
      related genes against a mouse model of hepatic fibrosis induced by CCl4 and
      ethanol-treated hepatocytes (ETH). Test mice were administered with CCl4 (2
      ml/mg) and hepatocytes were treated with 25 mM ethanol. BV was added to the final
      concentration of 0.05-0.5 mg/kg and 1-100 ng/ml for in vivo and in vitro testing,
      respectively. Fibrotic livers and ETH were used for the measurement of hepatocyte
      necrosis, pro-inflammatory cytokines and fibrogenic genes. BV suppressed CCl4
      induced hepatocyte necrosis markers of serum aspartate aminotransferase (AST) and
      alanine aminotransferase (ALT). It also inhibited the secretion of interleukin
      (IL)-1beta and tumor necrosis factor (TNF)-alpha. Moreover, BV inhibited CCl4
      induced expression of transforming growth factor (TGF)-beta1, alpha-smooth muscle
      actin (SMA) and fibronectin. Similarly, ETH exhibited significant suppression of
      IL-1beta, TNF-alpha, TGF-beta1 and fibronectin when cultured with BV. These
      results suggest that BV possesses anti-fibrogenic properties that are mediated by
      the suppression of pro-inflammatory cytokines and fibrogenic gene expression. BV
      has substantial therapeutic potential for the treatment of fibrotic diseases.

PMID- 20821824
TI  - Antioxidative and antiviral properties of flowering cherry fruits (Prunus
      serrulata L. var. spontanea).
AB  - The phenolic compounds of many fruits have been known to be efficient cellular
      protective antioxidants. In this study, antioxidative and antiviral properties of
      flowering cherry cultivars (Prunus yedoensis, Prunus sargentii, Prunus
      lannesiana, and Prunus cerasus) in Korea were investigated. The antioxidant
      property was assayed for specific activities including 2,2-diphenyl-1
      picrylhydrazyl (DPPH) hydroxy radical scavenging activity, reducing power
      capacity, and superoxide dismutase (SOD) like activity. In addition, antiviral
      activity was determined by inhibition studies on the infection cycle of porcine
      epidemic diarrhea virus (PEDV), measured as minimum concentration of cherry
      extracts that inhibited 50% of cytopathic effect (CPE) on PEDV. Our results show
      that the four varieties of cherries contain substantially high antioxidants and
      antiviral activities. In particular, P. cerasus contains higher antioxidants and
      antiviral activities as well as polyphenolic content than other varieties. Our
      data indicate that Korean native cherry cultivars could be beneficial supplements
      of dietary antioxidants and natural antiviral agents.

PMID- 20821825
TI  - Wild Panax ginseng (Panax ginseng C.A. Meyer) protects against methotrexate
      induced cell regression by enhancing the immune response in RAW 264.7
      macrophages.
AB  - Many traditional herbal medicines have been re-evaluated to determine whether
      they enhance immune responses. In this study, the possible use of wild Panax
      ginseng (WPG) for enhancement of host immunity in chemotherapy was investigated.
      In the cell proliferation assay, WPG significantly enhanced the proliferation of
      RAW 264.7 macrophages and protected against cell regression in macrophages
      treated with methotrexate (MTX). WPG induced the production of nitric oxide and
      the expression of inducible nitric oxide synthase and cyclooxygense-2 mRNA.
      Furthermore, WPG enhanced the production of cytokines including interleukin (IL)
      1alpha, IL-1beta, IL-6, tumor necrosis factor-alpha and granulocyte-macrophage
      colony-stimulating factor, and chemokines such as macrophage chemotactic protein
      1 and regulated upon activation, normal T-cell expressed and secreted (RANTES),
      regardless of MTX co-administration. Taken together, these results provide the
      first evidence that WPG triggers immune responses through the prevention of
      macrophage cell regression caused by MTX and functional activation of
      macrophages.

PMID- 20821826
TI  - Immunosuppressive effect of Cordyceps CS-4 on human monocyte-derived dendritic
      cells in vitro.
AB  - Cordyceps CS-4 (C.CS-4), a vegetative form of Cordyceps that contains the same
      active compounds as the fruit body, is widely used as a substitute of Cordyceps
      in China. A number of studies have shown that Cordyceps can positively stimulate
      the activation of T lymphocytes, B lymphocytes, natural killer cells, and
      macrophages. In our previous study, we found that C.CS-4 could inhibit the
      proliferation of CD4+ T cells in autoimmune diseases and prevent the lymphocyte
      infiltration in tissues. However, it is still unclear how the lymphocytes are
      regulated by C.CS-4. In this study, we investigate the effect of C.CS-4 on human
      monocyte-derived dendritic cells (Mo-DCs), which are generated from PBMCs by the
      treatment with GM-CSF and IL-4. It is observed that Mo-DCs pretreated with C.CS-4
      show an immature phenotype. Moreover, C.CS-4 significantly inhibits proliferation
      of CD4+ T cells, attenuates the production of cytokines in Mo-DCs and balances
      the Th1 and Th2 response in immune system. Our findings indicate that C.CS-4
      exerts the immunosuppressive effect through inhibiting the CD4+ T cells
      proliferation, regulating cytokine secretions of Th1 and Th2 response (Mo-DCs)
      and inducing phenotypic immature of Mo-DCs which may be related to the antigen
      presenting dysfunction.

PMID- 20821827
TI  - Methyl gallate inhibits the production of interleukin-6 and nitric oxide via down
      regulation of extracellular-signal regulated protein kinase in RAW 264.7 cells.
AB  - To determine the anti-inflammatory and analgesic activities of methyl gallate
      (MG) isolated from Galla Rhois, MG was studied in vivo for its analgesic
      activities using the writhing response in mice. Anti-inflammatory activity of MG
      was evaluated for NO and IL-6 production in RAW 264.7 cells. MG inhibited LPS
      induced NO and IL-6 production. Consistent with these observations, the protein
      and mRNA expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase
      2 (COX-2) were inhibited by MG. Moreover, MG suppressed the phosphorylation of
      ERK1/2 in LPS-induced RAW 264.7 cells in a dose-dependent manner. Taken together,
      the results of this study indicate that MG has anti-inflammatory effects.

PMID- 20821828
TI  - Eriobotryae folium extract suppresses LPS-induced iNOS and COX-2 expression by
      inhibition of NF-kappaB and MAPK activation in murine macrophages.
AB  - Eriobotryae folium (EF), the dried leaves of Eriobotrya japonica (Thunb.) Lindl.
      has been traditionally used to treat various diseases such as chronic bronchitis,
      cough, inflammation, skin diseases, and diabetes. In this study, we examined the
      effects of Eriobotryae folium extract (EFE) on lipopolysaccharide (LPS)-induced
      production of nitric oxide (NO) and prostaglandin E2(PGE2) in RAW264 murine
      macrophage cells. EFE suppressed LPS-induced NO and PGE2 production in a dose
      dependent manner. Consistent with these observations, EFE reduced the LPS-induced
      expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX
      2) at both protein and mRNA levels. Furthermore, EFE significantly inhibited LPS
      induced NF-kappaB binding activity, which was associated with the inhibition of
      IkappaB-alpha degradation. EFE also attenuated LPS-induced phosphorylation of
      mitogen-activated protein kinases (MAPKs) including extracellular signal
      regulated kinase (ERK), p38 MAPK and c-Jun N-terminal kinase (JNK). These results
      suggest that the anti-inflammatory properties of EF might result from inhibition
      of iNOS and COX-2 expression through the downregulation of NF-kappaB activation
      and MAPK phosphorylation in LPS-stimulated RAW264 cells.

PMID- 20821829
TI  - Tanshinone IIA increases mRNA expression of efflux transporters in cultured human
      intestinal cell.
AB  - Tanshinone IIA (TSNIIA) is the major active component of Salvia miltorrhiza,
      which is used in treatment of cardiovascular and cerebrovascular diseases
      traditionally in China. However, the low bioavailability of TSNIIA limits its
      clinical usage. To reveal the mechanism relating the absorption of TSNIIA, we
      detected the expression of efflux transporters in Caco-2 cells under the
      stimulation of TSNIIA. TSNIIA was purified and above 98% purity was confirmed by
      high-performance liquid chromatography. The expression of nine efflux
      transporters including BCRP, hPepT1, MCT and MRP1-6 in Caco-2 were verified by
      reverse transcription polymerase chain reaction, and the up-regulation of TSNIIA
      on the expression of these transporters was found by reverse transcription real
      time polymerase chain reaction. These results indicate that the low
      bioavailability of TSNIIA is partially due to its up-regulation on efflux
      transporters.

PMID- 20821830
TI  - Two antifungal components isolated from Fructus Psoraleae and Folium Eucalypti
      Globuli by bioassay-guided purification.
AB  - Fructus Psoraleae and Folium Eucalypti Globuli have long been used as Chinese
      medicines to treat various ailments such as asthma, eczema and dermatomycosis. In
      previous studies, their antifungal activities were demonstrated. The aim of the
      present study was to isolate active antidermatophytic compounds from their
      ethanolic extracts by means of bioassay-guided purification. Guided by the
      inhibitory activities on Trichophyton mentagrophytes, Trichophyton rubrum and
      Paecilomyces variotii, bakuchiol was isolated from the n-hexane fraction of
      Fructus Psoraleae whilst macrocarpal C was isolated from the n-hexane fraction of
      Folium Eucalypti Globuli. Both pure compounds could effectively inhibit the
      growth of dermatophytes in vitro. This is the first paper to report the isolation
      and identification of active antidermatophytic compounds from Fructus Psoraleae
      and Folium Eucalypti Globuli by the bioassay-guided purification.

PMID- 20821831
TI  - [Grouped papules on the left chest wall].

PMID- 20821832
TI  - [Comment on Hanken I, Schimmer M, Sander CA. Primary management and drug
      treatment of patients with toxic epidermal necrolysis. JDDG 2010; 8 341-347].

PMID- 20821834
TI  - [Toulouse Congress 2009: update on nephrology].

PMID- 20821833
TI  - [Comment on the letter "Toxic epidermal necrolysis" in JDDG 2010; 5 (8): 319-320
      und 341-347 ].

PMID- 20821835
TI  - Rating the level, quality, and strength of the research evidence.
AB  - Improving patient safety and quality requires more consistent application of best
      practices based on the strongest scientific evidence available. Although evidence
      based practice initiatives are increasingly being implemented in healthcare
      settings, clinicians may not have had the necessary preparation to accurately
      determine the overall strength of evidence supporting specific practice change
      recommendations. A particular issue is lack of clarity in use of the terms level
      of evidence, quality of evidence, and strength of evidence. This article
      clarifies the important differences among these terms.

PMID- 20821836
TI  - Impact of medication storage cabinets on efficient delivery of medication and
      employee frustration.
AB  - This prospective study examined the impact of medication cabinets installed
      outside patient rooms on nursing and pharmacy workflow. Storing medications and
      supplies outside patient rooms decreased nursing visits to the automated
      medication dispensing system, and nurses also reported fewer episodes waiting to
      access the system when it was busy. Benefits of this study include the ability to
      demonstrate the impact of medication cabinets on the medication storage and
      delivery process, prior to housewide implementation.

PMID- 20821837
TI  - Connecting recombination, nucleotide diversity  and species divergence in
      Drosophila.
AB  - The association between recombination rate and nucleotide diversity provides
      compelling evidence for the action of natural selection across much of the
      Drosophila melanogaster genome. This conclusion is further supported by the lack
      of association between recombination rate and nucleotide divergence between
      species. However, studies of other species, including other Drosophila, have not
      always yielded the same results. Our recent study measured these parameters
      within the D. pseudoobscura species group using next-generation sequencing and
      high-throughput genotyping technologies. We documented fine-scale variation in
      crossover rate within D. pseudoobscura, and we observed that crossover variation
      was strongly associated with nucleotide diversity only when measured at a fine
      scale. We also observed associations between crossover rate and sequence
      differences between D. pseudoobscura and its close relatives. These latter
      associations could have been driven in part by mutagenic effects associated with
      double-strand break repair, but we cannot exclude the possibility that it results
      primarily from shared ancestral polymorphisms. Overall, this work strongly
      underscores the importance of scale in testing for associations of recombination
      rate with other parameters, and it brings us one small step closer to
      understanding the role of natural selection and other evolutionary forces in
      shaping divergence among genomes.

PMID- 20821838
TI  - [For the primary prevention of the external causes of deaths].
AB  - Recently in Japan, the primary prevention for life-style related disease has been
      performed based on the comprehensive policies. Although more than 73-thousands of
      persons have died of external causes (i.e., accident, homicide, suicide),
      comprehensive preventive measures for them have not been established in Japan.
      The main objectives of injury research are to prevent the occurrence of injuries
      and to reduce their level of severity. Therefore, we medical staffs have to solve
      these problems and attend on the primary prevention of external causes of deaths.

PMID- 20821839
TI  - [Situation of the occurrence of unexpected accident].
AB  - The situation of the occurrence of an unexpected accident in Japan was outlined.
      The unexpected accident that cause of one's death statistics and can be put is a
      baby especially and a high rate. It is important to make the best use of the
      medical cause investigation for the relapse prevention of the unexpected
      accident.

PMID- 20821840
TI  - [Accidental poisoning and test for it].
AB  - There are many dangerous materials which cause poisoning, toxins or poisons, in
      our lives. We may suddenly suffer from the effects of these materials by
      inhalation or ingestion before we are aware of the risk. It is very important to
      identify toxins or poisons to prevent poisoning and treat the poisoned patients.
      We have to learn from previous accidents the way to resolve future problems.

PMID- 20821841
TI  - [Acute alcoholism and clinical examination].
AB  - Acute alcoholism causes consciousness disorder. It should be suspected when
      expired air smells of alcohol on arrival, or laboratory data suggest
      hyperosmolarity. In addition, an increase in the osmotic pressure gap suggests
      the possibility of acute alcoholism. The blood alcohol level can be estimated
      from the value.

PMID- 20821842
TI  - [Clinical examinations for the traffic accident patients].
AB  - Traffic accident is a leading cause of unintentional death and about six
      thousands annually died in Japan. As about one-million of persons suffer from
      traffic injuries, most of them seek medical attention. Therefore, medical staffs
      have to find the injuries accurately and treat immediately. Furthermore, the
      cause of accident should also be considered; why the accident was occurred, human
      error of the driver? To solve these problems, clinical examinations were needed.
      Medical staffs have to understand the characteristics of the traffic injuries:
      severe and multiple blunt injuries, popular injuries can be estimated with
      considering the pattern of the accident. Because some of the accidents are
      occurred when the driver is under the influence of alcohol and other drugs,
      screening of these subjects should be performed. Because the public is largely
      unaware of the preventable nature of traffic injuries, in addition to diagnose
      and treat accurately, we medical staffs have to attend on the primary prevention
      of the traffic injuries.

PMID- 20821843
TI  - Reaping the longevity dividend in time: biogerontology heavyweights advocate
      seeking late-onset interventions against aging.

PMID- 20821844
TI  - The hippocampus and the sense of smell. A review, by Alf Brodal. Brain 1947: 70;
      179-222.

PMID- 20821853
TI  - A prescription for better health: go alfresco.  Spending time outside might have
      some health benefits--and the 'greening' of exercise might have some more.

PMID- 20821854
TI  - Can aspirin do "that," too? Pain relief? Check. Cardiovascular disease
      prevention? Check. Protection against cancer? To be decided.

PMID- 20821855
TI  - When nerves get damaged. Peripheral neuropathy causes strange feelings of
      numbness and sometimes pain.

PMID- 20821856
TI  - Elevating your HDL game.  "Good" cholesterol levels can be increased in several
      ways, but taking niacin is the most effective.

PMID- 20821857
TI  - By the way, doctor. I am confused about omega-3 fats Are the different types
      equally good for you?

PMID- 20821858
TI  - Coming out of its shell. As fish stocks dwindle, we may find ourselves eating
      other sorts of seafood. Is shellfish a good alternative?

PMID- 20821859
TI  - How your feet work--and three steps for keeping them healthy.

PMID- 20821860
TI  - Agonies of the feet: four common foot problems.

PMID- 20821861
TI  - A guided tour down the foot aisle.

PMID- 20821862
TI  - By the way, doctor. I read your article about hammertoes in the May issue. Are
      flip-flops really that bad for your feet?

PMID- 20821863
TI  - Overdoing acetaminophen.  Many overdoses are accidental, so the FDA may require
      new warnings on the popular pain reliever and lower the daily limit.

PMID- 20821864
TI  - Epidemiological studies of coccidiosis in the domesticated fowl (Gallus gallus):
      IV. reciprocity between the immune status of floor-reared chickens and their
      excretion of oocysts.
AB  - Chickens reared in floorpens for 20 weeks and naturally infected with Eimeria
      acervulina, E. tenella, E brunetti and E. maxima suffered outbreaks of
      coccidiosis, subsequently developing immunity to disease caused by each species.
      Thereafter, fluctuations in immunity occurred, assessed by oocyst production
      following challenge, which did not produce clinical signs. These fluctuations
      where characterized by reciprocity between immunity to each species and the
      excretion of oocysts of the respective species. Hence, as birds approached the
      solidly immune state, oocyst excretion was almost completely inhibited. Immunity
      then began to wane, and oocyst excretion increased once more, stimulating
      immunity to reach such a level that oocyst excretion was again reduced, and so
      on. Immunity to each species developed independently in the same birds, and
      protection against disease was maintained for 20 weeks. Oocysts of E.acervulina,
      E.tenella, E.brunetti and E.maxima were first detected in the faeces of chickens
      after 2, 3, 4 and 9 weeks respectively. Respective peak counts occurred at 4, 4,
      12 and 9 weeks.

PMID- 20821865
TI  - Treating musculoskeletal disorders and pain. Foreword.

PMID- 20821866
TI  - [Opportune restructuring toward an internationally recognized journal].

PMID- 20821867
TI  - Epidemiological studies of coccidiosis in the domesticated fowl (Gallus
      gallus):III. The influence of the fowl's defaecation pattern on the excretion
      patterns of Eimeria tenella and E acervulina oocysts.
AB  - Fifteen 61-day-old chickens (3 lots of 5) caged singly were inoculated five times
      during 3 days with Eimeria tenella or E. acervulina to simulate field infections,
      or kept as uninfected controls. During a 32 h experimental period of constant
      illumination, beginning on the tenth day after the first inoculation, every
      dropping produced by the birds as recorded, collected separately and examines for
      oocysts. All the chickens exhibited a bimodal pattern of colonic defaecation
      between 07.30 and 15.30 GMT the next day, with peaks at 17.00 on the first day
      and 11.00 on the second. Caecal defaecation practically ceased between 17.30 and
      02.30 the next morning. Overall, colonic and caecal droppings were passed in the
      ratio 11.1:1. The patterns of oocyst excretion of both Eimeria species during the
      same 32-hour period exhibited peaks at 15.30 on the first day. Oocysts of either
      species were found both in caecal and colonic droppings. The chickens'
      defaecation pattern was superimposed upon the parasites' oocyst excretion
      patterns, the influence being more marked when lower numbers of oocysts were
      being excreted.

PMID- 20821868
TI  - Plasmodium gallinaceum and subsequent Eimeria acervulina infections in chickens
      are not synergistic.
AB  - Twenty-three years age, the first and only report of synergism between malarial
      and coccidial infections in chickens was published. In view of the potential
      commercial importance of this possible parasitic interaction in some parts of the
      world, and the lack of further supporting publications, this disease complex has
      now been reconsidered. An experiment on Plasmodium gallinaceum and Eimeria
      acervulina revealed no interaction of any kind between these species and a re
      examination, with statistical analysis, of the raw data on which the original
      publication was based shows that no evidence of synergism between malarial and
      coccidial infections in chickens has so far been produced.

PMID- 20821869
TI  - [Status survey on tuberculosis patients hospitalized at the National Hospital
      System--from a nursing viewpoint].

PMID- 20821870
TI  - [Evaluation of the precision in drug sensitivity tests at facilities testing acid
      fast bacteria--results in 2009].

PMID- 20821871
TI  - Packing of cholesterol molecules in human high-density lipoproteins.
AB  - High-resolution, proton-decoupled (13)C nuclear magnetic resonance spectra (90.55
      MHz) of human high-density lipoproteins (HDL) have been employed to investigate
      the physical state of unesterified cholesterol molecules in such particles. The
      cholesterol molecules in HDL(2), and HDL(3) were replaced with [4
      (13)C]cholesterol by either particle reconstitution or exchange from Celite. Two
      well-defined resonances from [4-(13)C]cholesterol molecules in HDL (2) and HDL(3)
      were observed at chemical shifts (delta) of 41.70 and 42.20 ppm, indicating that
      cholesterol molecules are present in two distinct environments. The signal at
      delta 41.70 arises from the C-4 atom of cholesterol molecules associated with the
      phospholipid monolayer at the surface of the particles. The resonance at delta
      42.20 is due to the 4-(13)C atom of cholesterol molecules dissolved in the
      cholesterol ester/triglyceride core. Decomposition of the two [4
      (13)C]cholesterol resonances shows that approximately 40% of the signal arises
      from molecules in the apolar core, with the remainder due to molecules in the
      surface. Spin-lattice relaxation time and line-width measurements indicate that
      the cholesterol molecules dissolved in the core are relatively disordered and
      mobile. The cholesterol molecules located among phospholipid molecules in the
      surface of the particle undergo relatively restricted, anisotropic motions. The
      chemical shifts and relaxation enhancements induced by the addition of
      paramagnetic ions to the aqueous phase indicate that the surface cholesterol
      molecules in HDL(2), and HDL(3) are exposed to the water and that the 4-(13)C
      atom of cholesterol is located in the region of the phospholipid acylcarboxyl
      groups.The NMR data indicate that the residence time for cholesterol molecules in
      either the surface or the core pools of HDL is greater than or equal to 10 ms.
      However, more than 90% of the unesterified cholesterol molecules in HDL are in a
      single kinetic pool for exchange with cholesterol molecules in other lipoprotein
      particles or cells. It follows that cholesterol molecules in the two
      microenvironments undergo fast exchange on the biological time scale and can
      equilibrate between the surface and core of HDL in the time scale 10 ms-ca. 300
      s. Neither the surface nor the core microenvironments of human HDL particles are
      saturated with cholesterol.

PMID- 20821872
TI  - [Proceedings of the 43rd seminar for clinical laboratory technician held by the
      Japanese Society of Clinical Pathology. June 8-12, 2009, Tokyo, Japan].

PMID- 20821873
TI  - The significance of the International Normalized Ratio (INR) for oral
      anticoagulant therapy.
AB  - For the laboratory control of oral anticoagulant treatment, the prothrombin time
      (PT) is used universally as the primary measurement. Important variability of the
      PT ratio (patient PT: mean health persons' PT) caused by different brands and
      batches of thromboplastin and instruments exists not only in North America, but
      throughout the world. To achieve uniformity of reporting, it is recommended that
      the PT ratio be transformed to the International Normalized Ratio (INR). This is
      possible if the thromboplastin manufacturer provides calibration data for each
      batch of thromboplastin. The INR scale facilitates the achievement of consensus
      on optimal therapeutic ranges for various clinical conditions. The INR will
      further improve the stability of anticoagulant treatment of travelling patients.

PMID- 20821874
TI  - Portable roots: Latin New Yorker community building and the meanings of women's
      return migration in San Juan, Puerto Rico, 1960-2000.
AB  - This article examines the life histories of women return migrants to Puerto Rico.
      It emphasizes the cultural aspects of return migration, especially how the
      narrators understood and expressed their collective identity as distinctive from
      Puerto Ricans born and raised on the island. These informants turned their life
      histories into morality fables of class mobility, gender role restriction, and
      social rejection on the island. These tales asserted their radical differences
      from both middle class-islanders, whom they had joined, and the working-class
      diaspora in New York City, from which they had come. The narrators also built an
      organization which reinforced their "Latin New Yorker" identity, invented on the
      island.

PMID- 20821877
TI  - Reconsidering Japan's underperformance in pharmaceuticals: evidence from Japan's
      anticancer drug sector.
AB  - Unlike its automobile or electronics industries, Japan's pharmaceutical industry
      did not become a global leader. Japan remains a net importer of pharmaceuticals
      and has introduced few global blockbuster drugs. Alfred Chandler argued that
      Japan's pharmaceutical firms remained relatively weak because Western firms
      enjoyed an insurmountable first first-mover advantage. However, this case study
      of the anticancer drug sector illustrates that Chandler's explanation is
      incomplete. Japanese medical culture, government policy, and research environment
      also played a substantial role in shaping the industry. In the 1970s and 1980s,
      these factors encouraged firms to develop little few effective drugs with low
      side effects, and profit from Japan's domestic market. But, these drugs were
      unsuitable to foreign markets with more demanding efficacy standards. As a
      result, Japan not only lost more than a decade in developing ineffective drugs,
      but also neglected to create the infrastructure necessary to develop innovative
      drugs and build a stronger pharmaceutical industry.

PMID- 20821878
TI  - "Every woman counts": a gender-analysis of numeracy in the Low Countries during
      the early modern period.
AB  - New evidence from Flanders and the Netherlands demonstrates that age heaping was
      gradually diminishing in large parts of the Low Countries during the sixteenth
      century, that (unexpectedly) almost no gender gap was apparent in the change
      (women even outperforming men at times), and that differences between town and
      countryside were small. These findings suggest an early rise in numeracy (or at
      least a "number sense") in both urban and rural areas, linked to demographic
      change and commercial development. Between 1600 and 1800, Flanders, in
      particular, seems to have lost its strong distinctiveness in this regard.

PMID- 20821879
TI  - The ethnicity of Ohio's strength culture.

PMID- 20821880
TI  - Health issues and medical care in the Ohio penitentiary, 1833-1907.

PMID- 20821881
TI  - "Dont DONT D-O-N-T" to "I do": Antoinette Brown Blackwell's relationship with
      marriage.

PMID- 20821882
TI  - Cacophonies of aid, failed state building and NGOs in Haiti: setting the stage
      for disaster, envisioning the future.
AB  - The January 2010 earthquake in Haiti was a catastrophe not only for the loss of
      life it caused, but also because it destroyed the very thin layer of state
      administrative capacity that was in place in the country. This article argues
      that the fragility of the Haitian state institutions was exacerbated by
      international strategies that promoted NGOs as substitutes for the state. These
      strategies have generated a vicious circle that, while solving immediate
      logistical problems, ended up weakening Haiti's institutions. However, the
      article does not call for an overarching condemnation of NGOs. Instead, it
      explores two cases of community-based NGOs, Partners In Health and Fonkoze, that
      have contributed to creating durable social capital, generated employment and
      provided functioning services to the communities where they operated. The article
      shows that organisations that are financially independent and internationally
      connected, embrace a needs-based approach to their activities and share a long
      term commitment to the communities within which they operate can contribute to
      bringing about substantial improvement for people living in situations of extreme
      poverty. It concludes that in the aftermath of a crisis of the dimension of the
      January earthquake it is crucial to channel support towards organisations that
      show this type of commitment.

PMID- 20821884
TI  - Rebuttal to Ottomanelli et al. Methods of a multisite randomized clinical trial
      of supported employment among veterans with spinal cord injury. J Rehabil Res
      Dev. 2009;46(7):919-30.

PMID- 20821883
TI  - From sex strangler to model citizen: Mexico's most famous murderer and the defeat
      of the death penalty.
AB  - Gregorio Cardenas Hernandez was Mexico's most infamous serial killer. After he
      confessed to killing four young women and burying them behind his home, he became
      the darling of the crime pages and criminological experts alike, and his case
      provoked a lively debate over the reinstatement of the death penalty in congress.
      The following essay uses his story, the policy debates it provoked, and his
      broader institutional odyssey in La Castaneda mental asylum (1943-1947) and
      Lecumberri prison (1948-1976) to explore how issues that affected Mexicans across
      the social spectrum were discussed and settled in a political system that was
      neither a dictatorship nor a democracy.

PMID- 20821885
TI  - [Guidelines of the National Consultant in the Field of Rehabilitation Medicine on
      the Organization and Conduct in Medical Rehabilitation, April 26, 2010.].

PMID- 20821886
TI  - Guidelines on the Diagnosis of Osteoporosis and Assessment of Fracture Risk in
      Poland of III Central European Congress on Osteoporosis and Osteoarthritis, XV
      Congress of the Polish Osteoarthrology Society and Polish Foundation of
      Osteoporosis.

PMID- 20821887
TI  - Position of the American Dietetic Association: food insecurity in the United
      States.
AB  - It is the position of the American Dietetic Association that systematic and
      sustained action is needed to achieve food and nutrition security for all in the
      United States. To eliminate food insecurity, interventions are needed, including
      adequate funding for and increased utilization of food and nutrition assistance
      programs, inclusion of food and nutrition education in such programs, and
      innovative programs to promote and support individual and household economic self
      sufficiency. More than 49 million individuals living in the United States
      experienced food insecurity in 2008. Negative nutrition and non-nutrition-related
      outcomes have been associated with food insecurity in children, adolescents, and
      adults, including substandard academic achievement, inadequate intake of key
      nutrients, poor health, increased risk for and development of chronic disease,
      poor disease management, and poor psychological and cognitive functioning.
      Registered dietitians and dietetic technicians, registered, can play key roles in
      ending food insecurity and are uniquely positioned to make valuable contributions
      through provision of comprehensive food and nutrition education; competent and
      collaborative practice; innovative research related to accessing a safe, secure,
      and sustainable food supply; and advocacy efforts at the local, state, regional,
      and national levels.

PMID- 20821888
TI  - [An opinion about mortality after tonsillectomy in recent years].

PMID- 20821889
TI  - [Who introduced bone substitution . . . Interview with Dr. Miklos Szendroi by B.
      Kiraly Gyorgyi].

PMID- 20821891
TI  - Exploring the causal machinery behind sex ratios at birth: does hepatitis B play
      a role?
AB  - The causal machinery underlying sex determination is directly relevant to many
      questions relating gender and family composition to social and economic outcomes.
      In recent work, Oster highlighted a correlation between parental hepatitis B
      carrier status and sex of the child. One of her analyses went further, speaking
      directly to causality. That analysis appeared to have answered an important
      question that had remained unresolved in medical and biological literatures
      namely, does chronic infection with hepatitis B cause male-skewed sex ratios at
      birth? Oster's creative empirical analysis appeared to suggest that it does;
      however, in this article I reassess the result and present evidence that, at the
      very least, the question remains open. Further investigation into questions
      around the causal machinery of sex determination is warranted in the social
      science literature, as well as in that of biology and medicine. However, my
      results suggest that it is extremely unlikely that chronic hepatitis B infection
      plays a biologically significant role.

PMID- 20821890
TI  - Degeneration and the origins of Mexico's war on drugs.
AB  - In the early twentieth century, the concept of "degeneration" helped to turn
      "drugs" into a problem of national importance in Mexico. By invoking this
      concept, Mexico's sanitary authorities secured provisions in the Constitution of
      1917 which specifically authorized a newly constituted Department of Public
      Sanitation to lead a nation-wide campaign against drug abuse. That Department
      then inaugurated Mexico's modern war on drugs when, in 1920, it declared a law
      governing the import and distribution of the opiates, cocaine, and marijuana
      nationwide. This essay examines the idea of degeneration and how it came to play
      this crucial role in the foundation of Mexico's modern war on drugs.

PMID- 20821892
TI  - The environmental impact of poverty: evidence from firewood collection in rural
      Nepal.
AB  - We investigate determinants of household firewood collection in rural Nepal,
      using 1995-96 and 2002-3 World Bank Living Standards Measurement Survey (LSMS)
      data. We incorporate village fixed effects, endogenous censoring, measurement
      error in living standards and heterogeneous effects of different household
      assets. We find no evidence in favor of the poverty-environment hypothesis. The
      evidence for the environmental Kuznets curve depends on the precise measure of
      living standards and time period studied. Firewood collections fall with a
      transition to modern occupations and rise with increasing population and
      household division. The local interhousehold collection externality is
      negligible, indicating that policy interventions are justified only by ecological
      considerations or nonlocal spillovers.

PMID- 20821893
TI  - Social capital and basic goods: the cautionary tale of drinking water in India.
AB  - This study uses micro-data from the 1998-99 Indian Time Use Survey (ITUS;
      covering 77,593 persons in 18,591 households in Gujarat, Tamil Nadu, Madhya
      Pradesh, Meghalaya, Orissa, and Haryana) to argue that time use data provides a
      natural metric for measuring "social capital" building activities and for
      distinguishing between the relative importance of "bonding" into groups or
      "bridging" within communities. The study examines the correlation between
      inequality in landownership, caste status, measures of local social capital, and
      whether or not a household will have to collect water. In India, the probability
      that a rural household fetches water is 4.8% and 9.1% lower in communities in
      which the average time spent on social interaction and community-based activities
      at the district-level doubles, but it is 18.9% greater when the time in group
      based activities doubles. Inequalities in landownership and home ownership are
      associated with considerably larger differences in local tap water availability.

PMID- 20821894
TI  - Community-based targeting and initial local conditions: evidence from Indonesia's
      IDT Program.
AB  - Community-based selection of social program recipients has the potential to
      benefit from local knowledge about individuals in need. However, this information
      advantage might be offset by local elite capture and administrative incompetency.
      Using data from Indonesia's antipoverty program, Inpres Desa Terttingal (IDT),
      this article investigates which preprogram conditions are associated with
      community-based targeting outcomes. Results show that wealthier and more unequal
      villages constantly target better. The findings for inequality suggest that,
      under certain political and program contexts, any possible influence of local
      elites might be overwhelmed by the ease of identification of the poor. Evidence
      is also found that villages with young, educated heads initially exhibit better
      targeting. However, they lose this advantage as the program design limits the
      continued monitoring of benefit allocations by the village heads.

PMID- 20821895
TI  - Strategic behavior and marriage payments: theory and evidence from Senegal.
AB  - This article proposes an original theory of marriage payments based on insights
      gained from firsthand information collected in the Senegal River valley. This
      theory postulates that decisions about the bride-price, which are made by the
      bride's father, take into account the likely effects of the amount set on the
      risk of ill-treatment of the wife and the risk of marriage failure. Based on a
      sequential game with three players (the bride's father, the husband, and the
      wife) and a matching process, it leads to a number of important predictions that
      are tested against Senegalese data relating to bride-prices and various
      characteristics of women. The empirical results confirm that parents behave
      strategically by keeping bride-prices down so as to reduce the risk of marriage
      failure for their daughters. Other interesting effects on marriage payments and
      the probability of separation are also highlighted, stressing the role of the
      bride's bargaining power in her own family.

PMID- 20821896
TI  - Does money matter? The effects of cash transfers on child development in rural
      Ecuador.
AB  - A large body of research indicates that child development is sensitive to early
      life environments, so that poor children are at higher risk for poor cognitive
      and behavioral outcomes. These developmental outcomes are important determinants
      of success in adulthood. Yet, remarkably little is known about whether poverty
      alleviation programs improve children's developmental outcomes. We examine how a
      government-run cash transfer program for poor mothers in rural Ecuador influenced
      the development of young children. Random assignment at the parish level is used
      to identify program effects. Our data include a set of measures of cognitive
      ability that are not typically included in experimental or quasi-experimental
      studies of the impact of cash transfers on child well-being, as well as a set of
      physical health measures that may be related to developmental outcomes. The cash
      transfer program had positive, although modest, effects on the physical,
      cognitive, and socioemotional development of the poorest children in our sample.

PMID- 20821897
TI  - "Compelled to their bad acts by hunger": three Irish urban crowds, 1817-45.

PMID- 20821898
TI  - Muslim women and foreign prostitutes: victim discourse, subjectivity, and
      governance.
AB  - In this article, we juxtapose the ways "Muslim women" and "foreign prostitutes"
      are commonly constituted as victims in media and politics. We analyze the
      functions of these two prototypical female victims in terms of the role they play
      in epitomizing "the problems of globalization" and in reinforcing the existing
      social and political structures. Victim discourse, when tied to the transnational
      proliferation of the sex industry and of (radical) Islam, has depoliticizing
      effects because it places nonindividual causes of victimization outside of "our"
      polity and society and casts the state as protector and neutral arbiter of
      national and global inequalities, marginalization, and social conflict.

PMID- 20821899
TI  - The problem of dependency: immigration, gender, and the welfare state.
AB  - This article discusses the regulation of marriage migration to Norway through an
      analysis of the subsistence requirement rule which entails that a person who
      wants to bring a spouse to Norway must achieve a certain level of income. Policy
      makers present two main arguments for this regulation. First, the subsistence
      requirement is a means to prevent forced marriage. Second, its aim is to prevent
      family immigrants from becoming a burden on welfare budgets. The major concern of
      both these arguments is that of dependency, either on the family or on the
      welfare state. The article investigates the representations of the "problems"
      underpinning this specific policy proposal and argues that the rule in question,
      and immigration policy more generally, needs to be analyzed with reference to the
      broader concerns and aims of welfare state policy and gender equality policy.

PMID- 20821900
TI  - Cabaret dancers: "Settle down in order to stay mobile?" Bridging theoretical
      orientations within transnational migration studies.
AB  - Adopting a transnational perspective has become essential in understanding the
      contemporary practices taking place across borders, especially with respect to
      migrants. In this article, I argue that we can distinguish two theoretical
      orientations within transnational migration studies: one theorizing the
      complexity of transnational processes and focusing on established migrants
      settled in host countries; and the second theorizing transnational practices on
      the basis of different but continuous forms of mobility. Using the example of
      cabaret dancers in Switzerland, I show how they develop a very specific form of
      transnationality, which corresponds at first sight to the second theoretical
      orientation. Some of them are genuinely "world travelers"-they work in erotic
      clubs in Switzerland, Japan, or Lebanon, go home regularly to visit their
      families, or continue their studies. As such, their transnational morphology is
      highly influenced by gender as well as by the (transnational) nature of the sex
      industry and the opportunities and legal structure in Switzerland. Nevertheless,
      to remain in circulation, the dancers need to develop a kind of mobility capital,
      which involves, paradoxically, becoming "sedentarized" to a certain degree in
      Switzerland. The article thus advocates a theoretical framework that better
      captures the experiences of settled as well as of circulatory migrants.

PMID- 20821901
TI  - A magic bullet for the "African" mother? Neo-Imperial reproductive futurism and
      the pharmaceutical "solution" to the HIV/AIDS Crisis.
AB  - On the basis of a close reading of popular and medical texts which address a
      debate over the ethics of clinical drug trials funded by the United States and
      designed mainly for sub-Saharan Africa, I argue that international public health
      discourse about infant HIV infection in that region reflects and legitimates a
      neo-imperialist, anti-reproductive justice ideology. Participants share a fetal
      centered logic that US-funded biomedicine must shoulder the burden of rescuing
      sub-Saharan Africa from itself by using the bodies of HIV-positive pregnant women
      to transmit biomedicine's magic bullet-antiretroviral drugs-to the next
      generation. The survival of the fetus, disguised as the well-being of the HIV
      positive woman and accomplished by the magic of biomedical research, becomes the
      survival of a region otherwise doomed by its present state of economic,
      political, and medical incapacity. This version of what queer theorist Lee
      Edelman (2004, No Future: Queer Theory and the Death Drive) calls "reproductive
      futurism" redounds to the benefit of the more explicitly women-hating and
      nationalist ideologies of still-powerful right-wing movements against
      reproductive and sexual rights.

PMID- 20821902
TI  - Europeanization in making policies against domestic violence in Central and
      Eastern Europe.
AB  - This article looks at how Europe matters in the development of policies against
      domestic violence, a gender equality field outside the core European Union (EU)
      conditionality criteria. By analyzing the concrete workings and uses of Europe's
      domestic violence policy-making in five Central and Eastern European countries,
      it identifies three mechanisms of Europeanization in the field and shows how
      together they work to expand the reach of the EU to this policy realm. The
      findings point toward an understanding of Europeanization based on social
      learning and dynamic, interactive processes of constructing what membership in
      the EU means in terms of domestic violence policy processes.

PMID- 20821903
TI  - Summary health statistics for U.S. adults: National Health Interview Survey,
      2008.
AB  - OBJECTIVES: This report presents health statistics from the 2008 National Health
      Interview Survey (NHIS) for the civilian noninstitutionalized adult population,
      classified by sex, age, race and ethnicity, education, family income, poverty
      status, health insurance coverage, marital status, and place and region of
      residence. Estimates are presented for selected chronic conditions and mental
      health characteristics, functional limitations, health status, health behaviors,
      health care access and utilization, and human immunodeficiency virus testing.
      Percentages and percent distributions are presented in both age-adjusted and
      unadjusted versions. SOURCE OF DATA: NHIS is a household, multistage probability
      sample survey conducted annually by interviewers of the U.S. Census Bureau for
      the Centers for Disease Control and Prevention's National Center for Health
      Statistics. In 2008, data were collected on 21,781 adults in the Sample Adult
      questionnaire. The conditional response rate was 74.2%, and the final response
      rate was 62.6%. The health information for adults in this report was obtained
      from one randomly selected adult per family. In very rare instances where the
      sample adult was not able to respond for himself or herself, a proxy was used.
      HIGHLIGHTS: In 2008, 61% of adults 18 years of age or over reported excellent or
      very good health. Fifty-nine percent of adults had never participated in any type
      of vigorous leisure-time physical activity, and 16% of adults did not have a
      usual place of health care. Twelve percent of adults had been told by a doctor or
      health professional that they had heart disease, and 24% had been told on two or
      more visits that they had hypertension. Twenty-one percent of all adults were
      current smokers, and 21% were former smokers. Based on estimates of body mass
      index, 35% of adults were overweight and 27% were obese.

PMID- 20821904
TI  - Summary health statistics for the U.S. population: National Health Interview
      Survey, 2008.
AB  - OBJECTIVES: This report presents both age-adjusted and unadjusted health
      statistics from the 2008 National Health Interview Survey (NHIS) for the civilian
      noninstitutionalized population of the United States, classified by sex, age,
      race, Hispanic or Latino origin and race, education, family income, poverty
      status, health insurance coverage (where appropriate), place of residence, and
      region of residence. The topics covered are respondent-assessed health status,
      limitations in activities, special education or early intervention services,
      injury and poisoning episodes, health care access and utilization, and health
      insurance coverage. SOURCE OF DATA: NHIS is a household, multistage probability
      sample survey conducted annually by interviewers of the U.S. Census Bureau for
      the Centers for Disease Control and Prevention's National Center for Health
      Statistics. In 2008, household interviews were completed for 74,236 persons
      living in 28,790 households, reflecting a household response rate of 84.9%.
      SELECTED HIGHLIGHTS: Nearly 7 in 10 persons were in excellent or very good health
      in 2008. About 37 million persons (12%) were limited in their usual activities
      due to one or more chronic health conditions. About 4 million persons (2%)
      required the help of another person with activities of daily living, and about 9
      million persons (4%) required the help of another person with instrumental
      activities of daily living. About 6% of children received special education or
      early intervention services. Among persons under age 65 years, about 44 million
      (17%) did not have any health insurance coverage. The most comrnon reason for
      lacking health insurance was cost, followed by a change in employment.

PMID- 20821905
TI  - Physician assistant role flexibility and career mobility.

PMID- 20821906
TI  - Fracture risk with PPIs and allergy to IV contrast.

PMID- 20821907
TI  - Is this lesion on the gum a worrisome growth?

PMID- 20821908
TI  - A day in the life: Timothy Sayles, MPAS, PA-C.

PMID- 20821909
TI  - Evaluation and management of the acute anterior shoulder dislocation.

PMID- 20821910
TI  - Disclosure of medical errors: the right thing to do.

PMID- 20821911
TI  - A rapidly growing lymphoma and tumor lysis syndrome in a toddler.

PMID- 20821913
TI  - Emergency or urgency? Effective management of hypertensive crises.

PMID- 20821912
TI  - The importance of staying current on rapid sequence intubation.

PMID- 20821914
TI  - Juvederm emerges as the newest hyaluronic acid dermal filler.

PMID- 20821915
TI  - Is banning direct-to-consumer advertising consistent with bioethical principles?

PMID- 20821916
TI  - Left flank pain following cardiac catheterization.

PMID- 20821917
TI  - Love's labors lost: sexual dysfunction in an adolescent male.

PMID- 20821918
TI  - Neuroblastomas.

PMID- 20821919
TI  - Twenty-one percent prevention...

PMID- 20821920
TI  - Obesity epidemic.

PMID- 20821921
TI  - Development of an obesity counseling model based on a study of determinants of
      intentional sustained weight loss.
AB  - BACKGROUND: Overweight and obesity are at epidemic proportions. This study
      examines the attitudes and actions of Oklahoma clinicians in obesity treatment,
      and the characteristics and perceptions of a subset of their patients who lost
      weight and were able to maintain weight loss. METHODS: Our study was a small
      mixed method study involving both surveys and interviews. Descriptive statistics
      were calculated, content analysis of interviews performed, and a model outline
      for obesity counseling was developed. RESULTS: Only 38% of the 66 clinicians
      surveyed try to motivate their patients to lose weight. Patients interviewed
      recommended that clinicians treat obesity as a medical problem. We incorporated
      themes from the patient interviews into the S-MASS model for obesity screening
      and counseling.This was positively reviewed by clinicians and patients.
      CONCLUSION: The S-MASS model can function as a guide to help the
      clinician/patient team develop successful strategies for weight loss and
      maintenance of weight loss.

PMID- 20821922
TI  - Improving the rate and quality of medicaid well child care exams in primary care
      practices.
AB  - BACKGROUND: Providing recommended well child care to children insured bythe
      Medicaid Program can be challenging. Members of the Department of Family and
      Preventive Medicine (DFPM) at the University of Oklahoma Health Sciences Center
      contracted to help practices improve the rates and quality of well child care
      visits within the Oklahoma Medicaid Program. METHODS: Sixteen pediatric and
      family medicine practices in three Oklahoma counties chose to participate in this
      quality improvement initiative. The records of Sooner Care-insured children age 0
      20 were reviewed for both rate and quality of well child care visits made during
      the previous twelve months. Performance feedback was provided. Practice
      guidelines, Sooner Care requirements, and tips from exemplary practices were
      provided. In two of the counties, a case manager helped practices with
      challenging patients. Practice Enhancement Assistants (PEAs) then helped
      practices implement a variety of strategies to increase visit rates and improve
      the quality of early and periodic screening, diagnosis, and treatment (EPSDT)
      visits. Information technology (IT) support was provided when needed. RESULTS:
      The average rates of visits, for all counties combined, increased. Visit rates
      increased more in the younger age groups (birth to two years). There was
      significant improvement in quality of visits. Rates and quality improved much
      more in some practices than in others. CONCLUSIONS: A combination of academic
      detailing, performance feedback, practice facilitation, case management, and IT
      support produced increases in the quality and rates of EPSDT exams.

PMID- 20821923
TI  - Increasing aspirin use among persons at risk for cardiovascular events in
      Oklahoma.
AB  - BACKGROUND: Cardiovascular disease (CVD), including coronary heartdisease
      (CHD)and stroke, is the leading cause of death in the United States and in
      Oklahoma; Oklahoma ranks 48th worst in CVD deaths.This paper will present
      Oklahoma-specific data and review current recommendations regarding aspirin use
      for the prevention of CVD events. METHODS: Average annual age-adjusted death
      rates were calculated. Oklahoma Behavioral Risk Factor Surveillance System
      (BRFSS) data were used to determine past history of CHD, risk factors for CHD and
      stroke, and aspirin use among persons 45 years and older. A literature review of
      recommendations regarding aspirin use was conducted. RESULTS: Between 2005-2008,
      14.8% of Oklahomans 45 years of age and older reported a history of coronary
      heart disease and 6.4% a history of stroke. Approximately 50% of Oklahomans 45
      years and older reported a history of hypertension and hypercholesterolemia;
      21.5% were current smokers and 16.0% had diabetes. Nearly 10,000 Oklahomans die
      annually from CHD or stroke. The United States Preventive Services Task Force
      recommends 81mg per day of aspirin for men 45 to 79 and women 55 to 79 years of
      age unless they are at risk for bleeding complications. Daily aspirin use in
      Oklahoma was 44-57% among those with risk factors but no history of CHD or
      stroke. Fewer than 50% of Oklahomans 45-79 years reported being counseled by a
      health professional to take aspirin. Among those persons without a history of CVD
      who were counseled by a healthcare professional regarding aspirin, 79% were
      taking daily aspirin compared to 18% among persons not counseled. Aspirin sales
      increased significantly in Stephens County following a multifaceted community
      based aspirin campaign. CONCLUSION: Low-dose aspirin is being underutilized as a
      strategy for reducing the excessive numbers of cardiovascular events and deaths
      in Oklahoma. Health professionals play an important role in educating patients
      about appropriate use of low-dose aspirin. Community-based interventions can also
      be effective.

PMID- 20821924
TI  - Preventing tobacco abuse: tar wars, the epic battle.

PMID- 20821926
TI  - Screening brief intervention and referral to treatment (SBIRT) saves lives and
      improves health.

PMID- 20821925
TI  - Prevention and mental illness: a new era for a healthier tomorrow.
AB  - The Department of Mental Health and Substance Abuse Services strives to provide
      the best possible care for Oklahoma communities through preventative programs and
      approaches such as QPR, Mental Health First Aid and mental health screenings. All
      of these techniques have been proven in providing adequate knowledge of risk
      factors in Oklahoma communities for mental health disorders and help to prevent
      those predisposed to mental illness from experiencing an onset of the disorder.

PMID- 20821927
TI  - The Oklahoma Health Improvement Plan.

PMID- 20821928
TI  - Tobacco in Oklahoma--2010.

PMID- 20821929
TI  - Dietary determinants of obesity.
AB  - Obesity has become a serious public health problem worldwide, and dietary
      composition can play a role in its prevention and treatment. However, available
      literature on the impacts of different dietary factors on weight change is
      inconsistent, or even conflicting. In this review, we briefly summarized the
      mechanisms and influences of several major dietary determinants of weight change,
      with a focus on their potential in the prevention of weight gain or regain. We
      discussed the intake of fat, protein, total carbohydrates, fruits and vegetables,
      fibre, free sugars, fructose and sugar sweetened beverages, dietary energy
      density, portion size, eating outside home, glycaemic index and glycaemic load.
      Popular weight loss diets, including the Atkins diet, Weight Watchers, Ornish
      diet and Zone diet, are also briefly discussed for their safety and efficacy in
      the maintenance of weight loss.

PMID- 20821931
TI  - High prevalence of nocturnal arterial hypertension and non-dipping in lung
      transplant recipients.
AB  - OBJECTIVE: An abnormal circadian blood pressure (BP) profile is associated with
      adverse cardiovascular and all-cause outcomes. It is highly prevalent after
      heart, liver and kidney transplantation. We aimed to assess the prevalence of an
      abnormal ambulatory BP pattern in lung transplant recipients (LTx). METHODS:
      Ambulatory BP monitoring (ABPM) was performed in 53 LTx and compared to those of
      42 control subjects matched for age, gender and daytime BP. In 19 patients in
      whom at least two recordings were performed, we compared the first and the last
      one. RESULTS: The non-dipping pattern (a less than 10% reduction in nocturnal BP)
      was more prevalent in LTx than in control subjects (89 versus 64%, P < 0.01).
      Nighttime BP was higher in LTx than in control subjects (P < 0.01 and < 0.001 for
      systolic BP (SBP) and diastolic BP (DBP), respectively). The nocturnal reduction
      of BP was lower in LTx than in control subjects (3 versus 8% for SBP and 6 versus
      13% for DBP, both P < 0.001). These results remained significant after adjustment
      for the presence of diabetes mellitus and creatinine clearance. In the 19
      patients in whom ABPM was performed twice (mean interval between the two
      recordings was 22 months), ambulatory BP values remained unchanged between the
      two recordings, although the number of antihypertensive agents was significantly
      higher. CONCLUSION: An abnormal circadian BP profile is highly prevalent after
      lung transplantation. It is observed consistently over prolonged periods of time.

PMID- 20821930
TI  - Less iodine injected for the same diagnostic performances: comparison of two low
      osmolar contrast agents (iobitridol 350 and iopamidol 370) in coronary
      angiography and ventriculography: a randomized double-blind clinical study.
AB  - OBJECTIVE: Mild reductions in iodine concentration could reduce acute side
      effects after intraarterial contrast media administration without affecting the
      quality of coronary artery images. This study was designed to show the
      equivalence in terms of image quality of two nonionic low-osmolar monomers,
      iobitridol 350 and iopamidol 370, and to compare their clinical safety in
      coronary angiography and ventriculography. METHODS AND RESULTS: In this
      multicentre, double-blind clinical trial, 98 adult patients were randomized to
      receive either iobitridol 350 or iopamidol 370. The image quality (primary
      evaluation criterion) of the whole examination was assessed using a 5-point scale
      (poor, fair, moderate, good, excellent). Secondary endpoints were the image
      quality per territory, diagnostic efficacy, practical comfort (5-point scale:
      impossible to evaluate, not practical, moderately practical, practical, very
      practical to use) and clinical safety (adverse events and vital signs). The
      proportions of examinations presenting with good or excellent global image
      quality was similar with both contrast media: 87.8% with iobitridol 350 vs. 89.8%
      with iopamidol 370. Similar results were observed when considering the image
      quality specifically for each major coronary artery and left ventricle. No
      difference between groups was found with respect to other secondary criteria.
      Adverse events occurred in 7 patients with iobitridol 350 (14.3%) and in 10
      patients with iopamidol 370 (20.4%). CONCLUSIONS: This study showed that, with
      regard to image quality and diagnostic efficacy and using a lower iodine
      concentration, iobitridol 350 was comparable to iopamidol 370 in adult patients
      requiring coronary angiography and ventriculography for diagnostic indications.

PMID- 20821932
TI  - Pioglitazone improves ventricular diastolic function in patients with diabetes
      mellitus: a tissue Doppler study.
AB  - OBJECTIVE: Pioglitazone treatment in type 2 diabetes mellitus produced
      significant improvements in glycaemic control, plasma lipids, blood pressure and
      inflammation. The aim of this study was to investigate the effect of pioglitazone
      on systolic and diastolic function in diabetic patients. METHODS AND RESULTS:
      Forty-nine diabetic patients were included in the study. The patients had never
      received thiazolidinedione therapy before. Clinical and echocardiographic
      variables were measured. 30 mg pioglitazone were administered. The patients were
      followed up for six months and all the measurements were re-evaluated for
      comparison. Body mass index (BMI) significantly increased after treatment.
      Fasting glucose, HbA1c and systolic blood pressure decreased. Insulin resistance
      improved and the HOMA-IR index decreased after pioglitazone treatment. Mean
      aortic diameter, left atrial systolic and diastolic volumes significantly
      decreased after therapy. Among diastolic function variables mitral E wave, E/A,
      ejection time and pulmonary vein peak reverse flow velocity (PVA) significantly
      increased whereas isovolumetric relaxation time (IVRT), isovolumetric contraction
      time (IVCT), deceleration time, E/E' and pulmonary vein late systolic flow (PVS2)
      decreased after pioglitazone therapy. Among tissue Doppler variables early (E)
      ventricular inflow velocities measured from the tricuspid lateral annulus, the
      mitral septal and lateral annulus, the anterior, inferior and posterior free wall
      significantly increased. Late (A) ventricular inflow velocities measured from the
      anterior, inferior free wall and the mitral septal annulus also increased.
      CONCLUSION: Pioglitazone treatment in type 2 diabetes mellitus produced
      significant improvements in measures of glycaemic control and diastolic
      ventricular function.

PMID- 20821933
TI  - Administration and effects of secondary prevention measures in coronary heart
      disease patients from Serbia according to gender and cardiometabolic risk.
AB  - BACKGROUND: The EUROASPIRE surveys showed high rates of modifiable cardiovascular
      risk factors in patients with coronary heart disease, identified after coronary
      artery bypass graft, percutaneous coronary intervention or myocardial infarction,
      with time trends in preventive cardiology over more than a decade. AIM: The aim
      of this study was to test the implementation of European recommendations for
      cardiac rehabilitation and secondary risk prevention programmes in the population
      of coronary heart disease patients from Serbia. SUBJECTS AND METHODS: A total of
      665 consecutive coronary heart disease patients (432 men, 233 women, aged 59.43
      +/- 11.62 years), admitted for specialized cardiovascular rehabilitation,
      interviewed and examined in relation to the presence of coronary risk factors and
      administration of secondary prevention measures, were enrolled in the study.
      RESULTS: High rates of smoking (27.67%), central obesity (58.05%), physical
      inactivity (61.50%) and adverse dietary habits (61.50%) were observed, as well as
      low frequency of patients who have reached recommended targets for waist
      circumference (41.95%), total cholesterol (40%), LDL-cholesterol (39.25%), HDL
      cholesterol (59.69%) and triglycerides (59.25%), while systolic (82.26%) and
      diastolic blood pressures (95.49%) were well regulated. A significantly lower
      rate of achieved therapeutic targets, despite widely used cardioprotective drugs,
      was observed in diabetic patients and patients with the metabolic syndrome.
      CONCLUSION: The results have shown a low proportion of coronary heart disease
      patients, especially with diabetes mellitus and metabolic syndrome, who reached
      the recommended therapeutic targets for cardiometabolic risk profile parameters,
      in spite of widely used cardioprotective drugs, and therefore clearly
      demonstrated the compelling need for more effective lifestyle management in the
      secondary prevention of coronary heart disease.

PMID- 20821934
TI  - Which is worst in patients undergoing primary angioplasty for acute myocardial
      infarction? Hyperglycaemia? Diabetes mellitus? Or both?
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of admission
      hyperglycaemia and/or diabetes mellitus (DM) on the outcomes of primary
      percutaneous coronary intervention (PCI) for ST-segment elevation myocardial
      infarction (STEMI). METHODS: 2482 consecutive patients with STEMI (mean age 56.5
      +/- 11.9, years, 2064 men) undergoing primary PCI between October 2003 and March
      2008 were retrospectively enrolled into the present study. Hyperglycaemia was
      defined as a venous plasma glucose level > or =200 mg/dl on admission. Patients
      were classified into four groups: non-diabetic/non-hyperglycaemic (NDNH, n=1806)
      patients; diabetic/non-hyperglycaemic (DNH, n=271) patients; non
      diabetic/hyperglycaemic (NDH, n=64); and diabetic/hyperglycaemic (DH, n=341).
      RESULTS: In-hospital mortality was higher in NDH (12.5%) compared to DH (8.5%),
      DNH (6.3%), and NDNH (0.9%) patients (P < 0.001). The composite end points
      including death, reinfarction, and target-vessel revascularization (major adverse
      cardiac events [MACE]) in the hospital were also higher in NDH (18.8%) compared
      with other patients (DH, 13.8% vs. DNH, 10.3% vs. NDNH, 3.7%, P < 0.001). The
      median follow-up time was 21 months.The Kaplan-Meier survival plot for long-term
      cardiovascular death was worst for DH patients (log rank P < 0.001). After
      adjustment for potentially confounding factors, NDH (OR 3.04, 95% CI 1.06-8.73; P
      = 0.03), and DH (OR 2.3,95% CI 1.29-4.09; P = 0.005), but not DNH (OR 1.22,95% CI
      0.57-2.6; P = 0.6) status, remained independent predictors of long-term
      cardiovascular mortality. CONCLUSIONS: STEMI patients with NDH represent the
      highest risk population for in-hospital mortality, and MACE. The worst outcomes
      for long-term cardiovascular mortality occur in DH patients.

PMID- 20821935
TI  - Association between hypertension and quality of life in a sample of Iranian
      adults.
AB  - BACKGROUND: This study aimed to investigate the association between hypertension
      and health-related quality of life in a sample of Iranian adults. METHODS:
      Samples were selected from the final phase of the Isfahan Healthy Heart Program
      (IHHP). A structured interview was conducted using a standardized questionnaire
      to obtain information on demographic and socioeconomic characteristics. Subjects
      with a systolic blood pressure of > or =140 mmHg or diastolic blood pressure of >
      or =90 mmHg or taking antihypertensive medication were regarded as hypertensive.
      Quality of life was assessed using the World Health Organization Quality of Life
      questionnaire BREF (WHOQOL-BREF), Persian version. The chi square test, t test,
      ANOVA and MANOVA were used as appropriate. A multiple regression model was used
      to show association of blood pressure and QOL. Statistical analysis was performed
      with the Statistical Program for Social Sciences software (SPSS) version 15. All
      differences were considered statistically significant at P < 0.05. RESULTS:
      Education, income, occupation and marital status were associated with
      hypertension. A negative association was observed between each domain of health
      related QOL and systolic blood pressure after adjustment for socio-demographic
      variables. Increasing systolic blood pressure was associated with a lower score
      of health-related QOL. In contrast, diastolic blood pressure was positively
      associated with health-related QOL. CONCLUSION: Due to a lower health-related
      quality of life hypertensive patients need more attention from health care
      providers.

PMID- 20821936
TI  - Effects of benazepril on cardiac fibrosis in STZ-induced diabetic rats.
AB  - OBJECTIVE: The present study was designed to explore the roles of MMP-2/TIMP-2 in
      cardiac fibrosis and to study the effects of benazepril, an angiotensin
      converting enzyme inhibitor (ACEI) on cardiac remodelling in streptozotocin(STZ)
      induced diabetic rats. METHODS AND RESULTS: Male Wistar rats were randomly
      divided into three groups: a normal control group (NC), a diabetes mellitus
      untreated group (DM) and a diabetes mellitus benazepril-treated group (DB).
      Diabetes mellitus was induced in the DM and DB groups by intraperitoneal
      injection of streptozotocin (60 mg/kg). DB rats were treated with benazepril 10
      mg/kg/day for 12 weeks by remedial perfusing of the stomach. In the DM group,
      compared with the NC group, the gene and protein expression of MMP-2 decreased
      while the TIMP-2 gene and protein expression increased in heart tissues, along
      with a markedly cardiac collagen deposition.All the above changes were attenuated
      by benazepril treatment in the DB group. CONCLUSIONS: The imbalance of MMP-2 and
      TIMP-2 expressions in heart tissues might participate in interstitial fibrosis in
      diabetic myocardiopathy. Benazepril may ameliorate cardiac fibrosis partly by
      regulating the MMP-2/TIMP-2 system.

PMID- 20821937
TI  - Impact of mitral valve repair in patients with mitral regurgitation undergoing
      coronary artery bypass grafting.
AB  - BACKGROUND: The benefit of concomitant mitral valve correction (replacement or
      reconstruction, MVR) and coronary artery bypass grafting (CABG) in patients with
      coronary artery disease and mitral regurgitation (MR) remains unclear. PATIENTS
      AND METHODS: 298 consecutive patients underwent CABG alone (n=196) or CABG+ MVR
      (n=102) between January 2003 and April 2008. Clinical data were collected and MR
      graded according to preoperative echocardiographic studies. Four severity grades
      of MR were determined and patients assigned accordingly. Echocardiographic follow
      up was performed postoperatively to assess heart and valve function. Multivariate
      logistic regression analysis was performed for perioperative morbidity and
      mortality. RESULTS: Patients were comparable within the groups regarding age,
      gender, NYHA-class, ejection fraction and number of graft vessels. Perioperative
      mortality (10.8% vs. 5.1%, P < 0.05) and degree of MR were higher among CABG+MVR
      patients. Among patients with moderate to severe or severe MR, postoperative
      echocardiography showed an improvement of mitral regurgitation in 95% of CABG+MVR
      and in 64% of CABG only patients. In patients with mild or moderate MR,
      improvement rates of both groups were similar (74% and 69%, respectively).
      Postoperatively, ejection fraction increased in both groups (CABG+MVR: 31.3 +/-
      8.5 to 36.4 +/- 11.2; CABG only: 29.9 +/- 6.1 to 33.3 +/- 8.1, P > 0.05).
      Significant predictors for peri-operative mortality were renal insufficiency,
      older age and NYHA class III/IV. CONCLUSIONS: For reduction of ischaemic MR,
      CABG+MVR is preferable in patients with moderate to severe or severe MR. Combined
      CABG+MVR procedures cannot be recommended for patients with a particular risk
      profile because of disproportionately high peri-operative mortality.

PMID- 20821939
TI  - Which strategies of cardiovascular health promotion and disease prevention for
      health professionals?

PMID- 20821940
TI  - Echocardiographic diagnosis of systemic AA amyloidosis presenting with acute
      liver failure.
AB  - We report the case of a 73-year-old man admitted to our hospital for acute
      hepatic failure. Antemortem diagnosis of systemic AA amyloidosis was made because
      of typical electrocardiographic and echocardiographic findings, in the absence of
      the classic clinical picture of kidney involvement.

PMID- 20821938
TI  - Associations of D-dimer and von Willebrand factor with atherosclerosis in
      Japanese and white men.
AB  - OBJECTIVE: D-dimer and von Willebrand factor (vWF) are associated with
      atherosclerosis. We recently reported that in a post-World War II birth cohort,
      Japanese men in Japan had lower levels of atherosclerosis than white men in the
      United States (U.S.). We examined whether the differences in D-dimer and vWF
      levels are associated with differences in atherosclerosis between the two
      populations. METHODS AND RESULTS: Population-based samples of 99 Japanese and 100
      white American men aged 40-49 years were examined for coronary artery
      calcification (CAC), carotid intima-media thickness (IMT), D-dimer, vWF, and
      other factors using a standardized protocol. When compared to white American
      men,Japanese had similar levels of D-dimer (0.22 +/- 0.28 vs. 0.19 +/- 0.24
      microg/L, respectively, P = 0.39) but significantly higher levels of vWF (124.1
      +/- 36.6 vs. 91.3 +/- 48.8%, respectively, P < 0.01). Japanese as compared to
      white American men had significantly lower prevalence of CAC (13.1 vs. 28.0%, P <
      0.01, respectively) and significantly lower IMT (0.61 +/- 0.07 vs. 0.66 +/- 0.08
      mm, P < 0.01, respectively). Japanese men had a significant positive association
      of D-dimer with the prevalence of CAC and a negative association of vWF with IMT,
      whereas white American men did not have any significant associations.
      CONCLUSIONS: In men aged 40-49 years, Japanese as compared to white Americans had
      similar levels of D-dimer and higher levels of vWF although Japanese had a
      significantly lower prevalence of CAC and IMT. These haemostatic factors are
      unlikely to explain the difference in atherosclerosis in these populations.

PMID- 20821941
TI  - Aortic coarctation endarteritis resulting in mycotic pseudoaneurysm and acute
      mediastinitis.

PMID- 20821942
TI  - Aortic coarctation: angioplasty and stenting of a total occlusion.
AB  - A 23-year-old man presented with dyspnoea and a blood pressure of 180/120 mmHg in
      both arms. Femoral and popliteal pulses were absent and there was a systolic
      ejection murmur along the left intercostal area.The chest X-ray showed rib
      notching and a normal cardiac silhouette.Transthoracic echocardiography showed a
      bicuspid aortic valve with a mild degree of left ventricular dysfunction and an
      interruption of the aorta 3 cm distally of the left subclavian artery. A 64-slice
      CT angiography confirmed an interruption with extensive collateral circulation.
      Angioplasty and implantation of a covered stent were successful. Six months after
      the procedure, the patient is asymptomatic and without any complication.

PMID- 20821944
TI  - An unusual right atrial mass: case report and review of the literature.
AB  - An 80-year-old woman presented with dyspnoea. Laboratory test results and ECG
      were normal but echocardiography revealed a right atrial round mobile mass
      measuring about 20 mm. CT scan and cardiac MRI showed a mass appending on the
      right atrial free wall above the tricuspid annulus, enhanced by contrast, without
      any thoracic or abdominal extension, and confirmed the diagnosis of a tumour.
      After surgical treatment, the pathological examination revealed a cardiac
      papillary fibroelastoma. This small primary cardiac benign neoplasm usually
      occurs on cardiac valves, but can also appear, as described here, in a non
      valvular localization. The diagnosis is, up to now, usually made by
      echocardiography, but CT and MR imaging could lead to a better description and
      analysis of this underestimated tumour.

PMID- 20821943
TI  - Carcinoid crisis with fatal coronary spasm in a small localized peripheral
      bronchial carcinoid.
AB  - Presumptive coronary artery spasm, with characteristic ST-segment elevation
      followed by ventricular arrhythmia and cardiac arrest, is a very uncommon
      manifestation of the carcinoid crisis and has been shown on angiography only once
      in a patient with co-existing extensive atheromatous disease. We present the
      history of a 70-year-old man with angiographically documented fatal diffuse
      coronary spasm in the absence of significant atheromatosis, related to an
      unprovoked carcinoid crisis caused by a small peripheral atypical carcinoid
      tumour in the absence of metastasis.

PMID- 20821945
TI  - A vascular tangle on coronary angiography.
AB  - We present a case of an obstructive atrial myxoma that was unexpectedly
      discovered during coronary angiography.

PMID- 20821946
TI  - Extremely enlarged right atrial appendage in paediatric idiopathic pulmonary
      hypertension.
AB  - We report an extremely rare case of a right atrial appendage aneurysm in
      idiopathic pulmonary arterial hypertension (PAH) identified at autopsy. The
      female patient was diagnosed with idiopathic PAH at the age of 7. Despite
      intensive treatment, she expired due to cardiac failure at the age of 18. At
      autopsy, initial thoracotomy revealed an extremely enlarged intrapericardial
      balloon-like chamber with characteristic horizontal stripes, which turned out to
      be a markedly dilated right atrial appendage. The histology of the lungs was
      compatible with idiopathic PAH. In cor pulmonale which may complicate PAH, the
      occurrence of a right atrial appendage aneurysm is extremely rare, although right
      ventricular dilatation is common. Improved prognosis and rare paediatric
      occurrence of idiopathic PAH may have disclosed the unprecedented flexibility and
      expandability of the atrial appendage in children.

PMID- 20821947
TI  - Diagnostic work-up of cardiac amyloidosis.

PMID- 20821949
TI  - Regulators extend their reign.
AB  - As the cogs begin turning to make health reform a reality, who wields the most
      power? Our readers put policymakers in Washington at the top of our ranking S of
      the 100 Most Powerful People in Healthcare. The Patient Protection and Affordable
      Care Act is a "great first step...but it really is only a first step. It sets us
      up to get into a whole body of work on changing the care delivery system", says
      Scott Armstrong of Group Health Cooperative in Seattle, who debuted at No. 38.

PMID- 20821948
TI  - Isolated anomalous left anterior descending artery arising from right sinus of
      Valsalva: a rare anomaly.

PMID- 20821950
TI  - NAIC draws 'blanks'. New forms, rules could hurt quality programs.

PMID- 20821951
TI  - What's So great about organic food?

PMID- 20821952
TI  - Farm vs. supermarket.

PMID- 20821953
TI  - The organic alternative.

PMID- 20821954
TI  - Nightmare on bedbug street.

PMID- 20821955
TI  - The vitamin-D debate.

PMID- 20821956
TI  - Subsidized then scrutinized. Reform will bring billions of dollars to the
      industry, but it could also deliver added examination of executive pay.
AB  - With more government involvement comes more government attention. That's the
      lesson about executive pay healthcare CEOs could learn as the reform law and its
      ramifications settle into place. "It's important for the people who are scraping
      together the dollars to pay their health insurance premiums to know what
      luxurious lives these CEOs are leading. They're living in a parallel universe",
      says U.S. Rep. Jan Schakowsky, left.

PMID- 20821957
TI  - Crowd control. Proposed bill could help ease overflowing EDs.

PMID- 20821958
TI  - Predictable scheduling. Nursing homes can boost quality, bottom line with
      'consistent assignment'.

PMID- 20821959
TI  - Curiosity can pay. Right questions can help find new revenue sources.

PMID- 20821960
TI  - Coaching with care. Patient advocates help guide post-hospital care in an effort
      to improve outcomes, reduce readmissions.

PMID- 20821961
TI  - Most prescribed pharmaceuticals. Ranked by total number of prescriptions, 2009
      (numbers in thousands).

PMID- 20821962
TI  - Is the FDA on drugs?

PMID- 20821963
TI  - Why J&J's headache won't go away.

PMID- 20821964
TI  - Be a better manager: live abroad.

PMID- 20821965
TI  - How anger poisons decision making.

PMID- 20821966
TI  - When emotional reasoning trumps IQ.

PMID- 20821967
TI  - Why men still get more promotions than women.
AB  - Though companies now invest heavily in mentoring and developing their best female
      talent, all that attention doesn't translate into promotions. A Catalyst survey
      of over 4000 high potentials shows that more women than men have mentors-yet
      women are paid $4600 less in their first post-MBA jobs, hold lower-level
      positions, and feel less career satisfaction. To better understand why, the
      authors conducted in-depth interviews with 40 participants in a mentoring program
      at a large multinational. All mentoring is not created equal, they discovered.
      Only sponsorship involves advocacy for advancement. The interviews and survey
      alike indicate that, compared with their male peers, high-potential women are
      overmentored, undersponsored, and not advancing in their organizations. Without
      sponsorship, women not only are less likely than men to be appointed to top roles
      but may also be more reluctant to go for them. Organizations such as Deutsche
      Bank, Unilever, Sodexo, and IBM Europe have established sponsorship programs to
      facilitate the promotion of high-potential women. Programs that get results
      clarify and communicate their goals, match sponsors and mentees on the basis of
      those goals, coordinate corporate and regional efforts, train sponsors, and hold
      those sponsors accountable.

PMID- 20821968
TI  - Four mistakes leaders keep making.
AB  - Again and again, senior managers fall into four behavioral traps that thwart
      organizational change. The behaviors are difficult to recognize and reverse
      because they serve to protect egos and prevent anxiety--but executives can
      overcome them. First, managers fail to set proper expectations. When they
      announce major directional changes or new goals, they don't spell out credible
      plans or specify who's accountable. Second, they excuse subordinates from the
      pursuit of overall goals, allowing people to remain preoccupied with their own
      units. Third, executives essentially collude with staff experts and consultants
      by going along with a deeply flawed contract: The experts agree to deliver and
      implement a "product" (a new system, for instance) but don't include measurable
      gains as part of the deal. Fourth, managers wait while associates overprepare.
      After challenging their employees to make needed improvements, they accept the
      response "Yes, but first we have to..." Finish the sentence: Train our people.
      Set up focus groups. Bring in Six Sigma. And so on. The best way to confront the
      traps is to conduct small personal experiments that rapidly produce tangible
      results, incur little risk of failure, and are confined enough to demonstrate a
      clear link between trial and outcome. For example, one iron plant addressed
      quality problems by targeting five areas for improvement, setting clear and
      measurable goals for each, and holding team Leaders accountable for outcomes. AlL
      five experiments succeeded and were extended to the rest of the plant. Quality
      problems eased up within 100 days and virtually disappeared a few months later.

PMID- 20821969
TI  - Kaiser Permanente's innovation on the front lines.
AB  - The Innovation Consultancy, a small team within the health care provider Kaiser
      Permanente, practices an expansive, service-focused version of innovation that is
      both rapid and economical in comparison with the conventional version. The team's
      members observe how health care providers interact with one another, with
      technology, and with patients, and how the patients respond. They take
      photographs, draw pictures, write stories, and try to capture experiences from
      the point of view of everyone involved. During KP MedRite, a project to reduce
      the error rate in dispensing medication to hospital patients, the team asked
      nurses what they thought was wrong with the dispensing process. The nurses
      usually replied, "Nothing". But when given a chance to make self-portraits, they
      would draw themselves with sad faces and frazzled hair. Interruptions appeared to
      be the leading cause of errors-so one of the resulting innovations was a bright
      yellow sash signaling that its wearer was not to be disturbed. KP's Chris
      McCarthy founded the Innovation Learning Network to accelerate knowledge transfer
      among peers in the nonprofit health care industry. One promising process that has
      emerged, Inflection Navigator, helps patients who've received a frightening
      diagnosis handle the consequent urgent tasks-follow-up tests, visits to
      specialists, decision making about treatment and care--with the aid of care
      coordinators. This innovation and others like it arise from a brand of creativity
      that transcends the media version of the health care debate.

PMID- 20821970
TI  - The boss as human shield.
AB  - As employees strive to do their jobs, they face threats to productivity from all
      quarters-disruptive technology, meddlesome superiors, senseless organizational
      practices, and abusive clients and customers. Sutton, of Stanford University,
      reminds us that the best bosses identify and slay those dragons, thereby
      protecting the time and the dignity of their people and enabling them to focus on
      real work. Self-awareness is the key to defending employees effectively. Good
      leaders resist their own tendency to exercise power: They keep meetings short,
      listen to their followers, and make it safe to disagree with the boss. They also
      work to reduce outside distractions by, for example, championing mornings free of
      e-mail or streamlining performance-review processes. When their own bosses are
      the problem, they occasionally defy orders. Once in a while, they encourage their
      people to overtly comply with misguided demands from on high without actually
      buying in to them. Good bosses fight enemies. They take the heat for their teams.
      They have their employees' backs. Stepping on to this battlefield requires
      humility, intelligence, and bravery. In leading the charge to make the workplace
      safe and productive, however, you may risk martyrdom. Don't lose sight of the
      need to retain your own political power as you defend against the institutional
      forces that threaten your employees. And remember that preserving your own well
      being will ensure that you have the energy to fight the good fight.

PMID- 20821971
TI  - [Levetiracetam modifies the pattern of audiogenic locomotive response in Wistar
      and Krushinsky-Molodkina strain rats].
AB  - The novel antiepileptic drug levetiracetam (keppra, 80 mg/kg, i.p.) produces a
      pronounced anticonvulsant effect on all parameters of the audiogenic locomotion
      response in Wistar rats, leading to the prevention of acoustic seizures
      approximately in 50% animals. Keppra injection also led to a decrease in the
      intensity of single audiogenic convulsive episode, a twofold prolongation of the
      latency of motor reaction, and a change in the pattern of seizure reaction toward
      increasing number of rats with "one-wave" response. In contrast, a lack of sound
      resistant animals and the change from one- to two-wave audiogenic response were
      observed in Krushinsky-Molodkina strain rats.

PMID- 20821972
TI  - [Simultaneous AMPA receptor potentiation and NMDA receptor blockade as strategy
      for creating effective stimulants for cognitive functions].
AB  - New compounds representing derivatives of acyclic isothioureas have been
      synthesized, which are capable of simultaneously activating AMPA receptors and
      blocking NMDA receptors. In order to produce cognitive-stimulating effect, of
      principal importance is the pathway of NMDA receptor blockade produced by the
      drug. Positive influence is due to the blockade of NMDA receptors either by
      mechanism of rapid dissociation of intrachannel site or by inhibition of NR2B
      subunit of NMDA receptor. Substances that only potentiate AMPA receptor currents
      or only block NMDA receptors have less pronounced effect on memory than
      substances with ability to simultaneously potentiate AMPA receptor currents and
      block NMDA receptor currents. Based on these results, it is concluded that the
      simultaneous potentiation of AMPA receptors and blockade of NMDA receptors may be
      a new approach to the stimulation of cognitive functions.

PMID- 20821973
TI  - [Effect of nootropes on quantitative changes in the rat cerebral cortex GABA(A)
      receptor complexes under experimental hypokinesia conditions].
AB  - The influence of picamilon and piracetam on the quantitative changes in the
      central GABA(A) macromolecular receptor complexes in the rat brain has been
      investigated under the experimental conditions of hypokinesia. It was found that
      the injection of these nootropes under the conditions of 7-day hypokinesia and 4
      day recovery period did not show visible changes in the amount of active GABA(A)
      receptors. However, the injection of picamilon under the conditions of 15-day
      hypokinesia and 8-day recovery period showed a tendency to restoration of the
      number of active GABA(A) receptors.

PMID- 20821974
TI  - [Effect of cysteine lithium salt on lipid peroxidation in the model of
      dopaminergic system disorder].
AB  - The antioxidant activity of a newly synthesized compound, cysteine lithium salt,
      was discovered using methyl oleate oxidation model of dopaminergic system
      disorder. Experimental data show that injection of the synthesized compound in
      animals with experimentally induced L-DOPA brings to normalization effect
      conditioned by inhibiting free radical reactions in the nuclear and mitochondrial
      fractions of brain cells. Antioxidant effect of the synthesized compound is
      related to its chemical structure that contains cysteine--an agent involved in
      the biosynthesis of glutathione, which is a component of glutathione peroxidase
      and glutathione reductase enzymes participating in the antiradical protection
      system.

PMID- 20821975
TI  - [Delayed effect of 2-amino-4-acetylthiazolo[5, 4-b]indole hydrobromide on
      physical capability in mice].
AB  - The effect of 2-amino-4-acetylthiazolo[5, 4-b]indole hydrobromide (compound VM
      605), a new antihypoxic drug and an analog of antihypoxant amtizole, on physical
      capability was studied in mice under swimming test conditions. The action of VM
      605 depended both on the terms of testing upon administration of the drug and on
      the psychoemotional type of test animals. Maximum increase of the physical
      capacity in test mice was observed in delayed (up to 72 h) period after drug
      injection rather than in early (within 1-3 h) period. This increase was more
      typical of emotionally active and high-stress-resistant mice that were
      preliminarily selected in open field and forced swimming tests. It is suggested
      that delayed effects of VM-605 on physical capacity are related to the formation
      of active metabolites of the drug.

PMID- 20821976
TI  - [Efficacy of cytoflavine in treating traumatic toxicosis].
AB  - Experiments on rats showed that traumatic toxicosis (crush syndrome) was
      accompanied with hypotension, bradycardia, reduction in temperature, breath
      frequency, and oxygen intake, and violation of acid-base buffer state with
      elevation of lactate acidosis in the blood serum that is typical of shock
      performance. Substrate combined antihypoxant cytoflavine (1.5 ml/kg) administered
      systemically to rats immediately after decompression, increased percentage of
      survived rats and recovered the main indexes of functional systems and acid-base
      buffer state 12 h after trauma, which provided general protection of rats against
      traumatic toxicosis.

PMID- 20821977
TI  - [Effect of erythropoietin on blood oxygen transport in rats during cold exposure
      and subsequent rewarming].
AB  - Effect of erythropoietin (EPO) preparation (epocrine) on the blood oxygen
      transport in rats exposed to cold (120 min in a water-cooled box at 19 degrees C)
      and then rewarmed (next 120 min at a mean heating rate of 0.06 degrees C/min) has
      been studied. The administration of EPO reduced the body temperature fall at the
      end of cold exposure and enhanced its rise during the rewarming stage. The effect
      of EPO in tested rats is associated with a decrease in the hemoglobin affinity to
      oxygen, which increases the oxygen supply of tissues and improves the organism
      adaptability to cold.

PMID- 20821978
TI  - [Combined cycloferon treatment of tuberculosis in patients infected with HIV].
AB  - Outcome of treatment of 102 patients co-infected with HIV and tuberculosis
      hospitalized at Second Municipal Tuberculosis Hospital (St. Petersburg) is
      analyzed. The median period of follow up was 8 weeks. In order to select the
      optimum treatment scheme, all patients were divided into three groups (I-III).
      Group I (51 patients) received, in addition to antituberculosis medications,
      cycloferon 600 mg tablets on alternate days. Group II (16 patients) received
      alpha and gamma interferons (Interal injection, 3 MU and Ingaron injection,
      500,000 on alternate days) in combination with antituberculosis medications.
      Control group III (35 patients) received antituberculosis treatment plus placebo.
      Assessment of the outcome of TB treatment upon 8 weeks of follow up showed a
      remarkable improvement of clinical and immunological conditions in the patients
      who received interferons and cycloferon.

PMID- 20821979
TI  - [Cardiotoxic effects of breast cancer chemotherapy and their possible
      correction].
AB  - Clinical data are reported upon the examination of a group of 160 women aged 18
      55, suffering of a breast cancer and subjected to polychemotherapy using various
      cytostatic schemes: (I) standard CAF scheme, course repetition each 4 weeks; (II)
      alternating CAF and AVCFM schemes (intermittent introductions), a total of 4
      courses. For the reduction of the cardiotoxic effects of anthracyclines, one part
      of patients was given an antioxidant preparation of amber acid--Reamberin--whose
      administration substantially decreased both the frequency of cardial complaints
      and the expression of clinical manifestations of the astheno-neurotic syndrome
      and prevented the occurrence of systolic and diastolic dysfunction of myocardium
      and the heart rhythm and conductivity disturbances.

PMID- 20821980
TI  - [Nanopharmacology: not a constituent part of homeopathy].

PMID- 20821981
TI  - [Alternative experiments in pharmacology and radiobiology (education experience
      at the Molecular Pharmacology and Radiobiology Division of the Department of
      Medical Biology of N I Pirogov Russian State Medical University)].

PMID- 20821982
TI  - [New data on morphogenesis of gunshot bone injuries].
AB  - Studies with the use of atomic-force and scanning electron microscopy yielded new
      data that extend our knowledge of the complicated process underlying bone tissue
      degeneration as a result of its interaction with a high-speed injurious
      projectile. These data open up good prospects for the study of gunshot wounds and
      provide novel opportunities for forensic medical examination and diagnostics
      including confirmation of gunshot origin of the injury, elucidation of the
      properties (in the first place, energetic characteristics) of the injurious
      projectile, and determination of the wound size.

PMID- 20821983
TI  - [Forensic medical evaluation of thanatogenesis in craniocerebral injury].
AB  - Causes of death in survivors of a craniocerebral injury are described. Transition
      of cerebral tanatogenesis to pulmonary one during the hospital stay of the
      affected subjects has been documented. Respiratory distress syndrome in adult
      patients is shown to play an important role in the development of pneumonia after
      a craniocerebral injury.

PMID- 20821984
TI  - [Experimental simulation of blunt cardiac trauma].
AB  - This paper was designed to analyse the main experimental models of blunt cardiac
      trauma proposed during a period of more than 100 years beginning from the study
      of the Italian scientist Felice Meola dated to the 1870s till the present time.
      The analysis demonstrated that even a mild injury to the anterior chest wall in
      the projection of the heart may cause serious changes in hemodynamics and ECG
      characteristics. It was shown that various methods employed to simulate blunt
      cardiac trauma place potential constraints related to the design of experiments.

PMID- 20821985
TI  - [Assessment of injuries to the neck and dentomandibular system complicated by the
      infectious process].
AB  - The objective of the present work was to consider problems pertaining to forensic
      medical examination of injuries to the neck and dentition system complicated by
      pyoinflammatory processes. Two clinical observations are reported to illustrate
      significant difficulties encountered by forensic medical experts during
      assessment of the severity of harm inflicted to human health in the cases
      requiring differential characteristic of injuries, evaluation of opportuneness
      and completeness of the provided medical aid, and the role of these factors in
      the development of fatal pyoseptic complications. Special emphasis is laid on the
      analysis of possibilities to attain these goals based on the "Medical criteria
      for the assessment of severity of harm inflicted to human health" (2008).

PMID- 20821986
TI  - [Characteristics of skin and bone injuries in the cadavers inflicted by rat
      teeth].
AB  - The authors describe the morphological picture of skin and bone injuries
      inflicted by rat bites. Analysis of traces left by rat incisors is presented.
      Mechanism of their action and conditions for the appearance of injuries on human
      cadavers is considered.

PMID- 20821987
TI  - [Prospects for using chemiluminescence technique for the solution of certain
      topical problems of forensic medicine].
AB  - Chemiluminescent techniques are employed in forensic medicine for the elucidation
      of such important problems as prescription of death coming, prescription and life
      timeliness of a mechanical injury. Oxidation of free radicals is known to play an
      important role in pathogenesis of cardiovascular diseases. The present study
      demonstrates the necessity of investigation of chemiluminescent properties of the
      blood and tissue homogenates during the postmortem period for differential
      diagnosis of the causes of sudden death.

PMID- 20821988
TI  - [Application of spectral methods for the identification of rubber-sole footwear
      as a trauma implement].
AB  - Kicking to death is estimated to account for nearly 0.5% of all forensic medical
      autopsies and an appreciable share of murders. Meanwhile, the true number of such
      cases seems to be much in excess of these statistical data due to the difficulty
      of ascertaining the nature of injuring tools. This paper reports the results of a
      comprehensive medico-criminalistic investigation of the traces left by kicking
      with rubber-sole footwear. It is shown that in certain cases the use of spectral
      techniques (X-ray fluorescence and emission-spectral analysis) in combination
      with autopsy data, results of comparative forensic biological studies, and
      inquest information makes it possible to identify a concrete trauma weapon.

PMID- 20821989
TI  - [Differential diagnosis of ethanol poisoning, alcohol withdrawal, and chronic
      alcoholic intoxication from the changes in neurons and macroglyocytes in the
      cerebral cortex].
AB  - The present paper reports results of a quantitative morphometric study of neuron
      and macroglyocyte populations in layers III and V of the brain somatosensory
      cortex in subjects with ethanol poisoning (EP), alcohol withdrawal (AW), and
      chronic alcoholic intoxication (CAI). The study was carried out during a more
      than 7-day period of abstinence in patients presenting with early manifestations
      of alcoholic illness. In subjects with ethanol poisoning, acute swelling of
      neurons in layer III was more pronounced than in layer V. Dynamic changes in the
      number of satellites near bodies of slightly affected neurons were recorded in
      layer III in patients with EP and AW as well as during the long-term break in
      intoxication. Layer V in EP, AW, and CAI exhibited phagocytosis of neurons, an
      elevated number of macroglyocytes and their enhanced proliferation along the
      course of blood vessels. The morphological changes of neurons and macroglyocytes
      under the above conditions can be categorized in terms of their degeneration rate
      from the beginning of the abstinence period into transient (disappearing within 7
      days), persistent, and combined.

PMID- 20821990
TI  - [Forensic chemical investigation of alcohol-containing liquids contained
      polyhexamethylene guanidine hydrochloride and diethylphthalate].
AB  - Alcoholism remains one of the main causes of premature death in the population of
      Russia. Hence, the importance of the problem of uncontrolled distribution and
      consumption of surrogate alcoholic products, such as alcohol-containing liquids
      of uncertain origin. The objective of the present study was to detect ethyl
      alcohol, polyhexamethylene guanidine hydrochloride, and diethylphthalate in
      disinfectant liquids, biological fluids and human tissues and to analyse
      qualitative and quantitative composition of these materials.

PMID- 20821991
TI  - [Organization of the expert work of specialists from Perm regional Forensic
      Medical Bureau after the fire in the "Khromaia loshad'" club].
AB  - The paper summarizes the positive experience with the organization and
      optimization of coordinated activities of different divisions of the Perm
      regional Forensic Medical Bureau during the fire in the Khromaya loshad' (Lame
      horse) club in December 2009. The work of the Bureau personnel exemplifies
      adequate actions of specialists in a mass casualty incident with practically
      simultaneous admission of a large number of corpses. Despite lack of time, the
      staff of the Bureau managed to opportunely and effectively accomplish large
      volume of forensic medical examination without recruitment of additional
      workforce and means from other regions of the country.

PMID- 20821992
TI  - [The ultrasound-assisted method for the extraction of cellular elements from
      saliva traces left on cigarette butts].
AB  - Specimens for cytological studies prepared from the traces of saliva left on
      cigarette butts using an ultrasound bath contained 5-7 times more epithelial
      cells than samples obtained by the traditional method. The new technique requires
      much less material for the analysis. It was validated during forensic medical
      examination of saliva traces left on cigarette.

PMID- 20821993
TI  - [On the necessity to prepare new "Rules for the organization and conduction of
      forensic biological examination and studies by the State Forensic Examination
      Boards of the Russian Federation"].
AB  - The author substantiates the necessity to prepare new "Rules for the organization
      and conduction of forensic biological examination and studies by the State
      Forensic Examination Boards of the Russian Federation". Their long-term absence
      of the reviewed document has negatively influenced the quality of work of these
      facilities. The structure and contents of the three previous versions of the
      Rules for the study of material evidence (1934, 1956, and 1996) are analysed. The
      structure of the new variant is designed to optimize the work of forensic medical
      examination bureaus and the performance of relevant studies.

PMID- 20821994
TI  - [Historical aspects of the problem of work capacity evaluation].
AB  - This article addresses one of the as yet unresolved issues pertaining to forensic
      medical examination of certain health problems, namely the absence of an accurate
      universally accepted approach to the interpretation of the term "working
      capacity". Historical prerequisites for the evolvement of such notions as
      "economic criterion" and "disability percentage tables" are discussed with
      special reference to the estimation of the degree of harm to human health.
      Analysis of the literature data is used to compare different points of view of
      the problem and ascertain their validity.

PMID- 20821996
TI  - What Medicare means for my practice.

PMID- 20821995
TI  - [Iosif Vasil'evich Bertenson, an organizer of forensic medical examination in the
      Sankt-Peterburg region].
AB  - The paper describes the life and professional work of I.V. Bertenson, MD, the
      first medical inspector of the Sankt-Peterburg guberniya (region), distinguished
      forensic medical examiner, surgeon, hygienist, historian of medicine and
      organizer of health services in this country. The versatile activities of I.V.
      Bertenson are exemplified by his work as the editor of the journal "Arkhiv
      sudebnoy meditsiny and obshchestvennoy gigieny (Archive of Forensic Medicine and
      Public Hygiene)", and the chairman of the 5th Pirogov Congress. The materials for
      the paper were borrowed from the Sankt-Peterburg Central State Archive and pre
      revolutionary press publications.

PMID- 20821997
TI  - All Medicare, (almost) all the time...and loving it!

PMID- 20821998
TI  - Saying no to Medicare.

PMID- 20821999
TI  - Know when treatment relationship ends.

PMID- 20822000
TI  - [Chromosome characteristics of three Coptis species].
AB  - In the present paper, three Coptis species, collected from Sichuan and Chongqing,
      China, were used for karyotypic analyses. The results indicated that both C.
      chinensis and C. omeinensis were diploid with chromosome 2n = 2x = 18, and C.
      deltoidea was an autotriploid with chromosomes 2n = 3x = 27, which explained why
      this species was morphologically so isolated from other species and its sterile
      and narrow distributing regions. The relationship between C. chinensis and C.
      omeinensis based on chromosome data was discussed. The probable origin of C.
      deltoidea was also suggested.

PMID- 20822001
TI  - [Effects of soil factor on active components of Radix Ophiopogonis].
AB  - OBJECTIVE: To study the effects of soil factors on the active components in Radix
      Ophiopogonis. METHOD: The content of polysaccharide, flavonoids, saponins, water
      soluble extract and inorganic elements in Radix Ophiopogonis gathered from 7
      different places were compared, physical and chemical properties and inorganic
      elements of soil were analyzed. The path and grey connection analysis were
      applied for studying the effects on the active components of Radix Ophiopogonis.
      RESULT AND CONCLUSION: The concentrations of mineral elements in plant were
      mainly adjusted by active absorption. The active components in Radix Ophiopogonis
      was primarily effected by soil enzyme activity, the other important factors were
      potassium, pH, and organic matter. K, Fe, Mn, B, Ba, Zn of soil also had much
      influence on it then others inorganic elements.

PMID- 20822002
TI  - [Nutrient change in Lonicera macranthoides during cutting propagation process].
AB  - OBJECTIVE: To study the dynamic change of nutrient in the cuttings of Lonicera
      macranthoides. METHOD: In the process of growing, soluble sugar, starch, soluble
      protein, total nitrogen and total phosphorus in the leaves and basal of cuttings
      were determined. RESULT: The relationship between nutrient dynamic change and
      rooting was as follows: the content of the soluble sugar and starch in leaves and
      basal of cuttings was firstly decreased then increased. The soluble protein in
      leaves was also firstly decreased then increased, and in basal of cuttings, it
      showed a downtrend, it decreased slowly at the later stage. The total nitrogen
      content in leaves and basal showed a downtrend and decreased slowly later. The
      C/N ratio in leaves and basal of cuttings was firstly decreased then increased.
      The trend of total phosphorus in leaves was firstly decreases and then increases,
      and in basal of cuttings, it decreased gradually. CONCLUSION: There exists close
      relationship between the adventitious root formation nutrients level, and main
      nutrients play an important role in regulating formation of adventitious root.

PMID- 20822003
TI  - [Quality grading of artificial tuber seed of Pinellia ternata].
AB  - OBJECTIVE: To establish the seed quality grading standard of artificial tuber of
      Pinellia ternata. METHOD: Hundred-grain weight, moisture content, germination
      rate, viability, single-grain diameter, purity and visual form of mature
      artificial tuber seed from tissue culture of P. ternate were determined. The key
      indicator and reference indicators for artificial tubers quality grading were
      defined statistically by SPSS analysis. RESULT: Germination rate and viability
      were the primary indicators, hundred-grain weight, moisture content and purity
      were important reference indicators. CONCLUSION: The quality of each grade should
      reach the following requirements: for first grade, hundred-grain weight > 10 g,
      moisture content > 70%-80% , germination rate > 80%, viability > 85%, single
      grain diameter > 0.7 cm, purity > 80%; for second grade, hundred-grain weight 8
      10 g, moisture content > 70%-80%, germination rate 60%-80%, viability 70%-85%,
      single-grain diameter 0.3-0.7 cm, purity 75%-80%; moisture content > 70%-80%, and
      the others don't reach second grade was the third grade.

PMID- 20822004
TI  - [Antagonistic mechanisms of trichoderma spp. against Phytophthora nicotianae].
AB  - Antagonistic mechanisms of Trichoderma viride M3, Tv04-2, and T. harzianum ThB,
      were studied against Phytophthora nicotianae, the pathogen of stem blight disease
      on Schizonepeta tenuifolia by dual-culture, hydrolase activity, volatile and
      nonvolatile substances. Results indicated that competitive, mycoparasitism and
      antagonism were the antagonistic mechanisms of three Trichoderma spp. against P.
      nicotianae. Hydrolase activity showed that M3 was the highest for beta-1, 3
      glucanases activity while ThB was the highest for proteases activity among the
      three T. strains, and they could produce volatile and non-volatile substances,
      also.

PMID- 20822005
TI  - [Establishment of transformation system in mulberry and biosynthesis of
      quercetin].
AB  - OBJECTIVE: To establish the transformation system of mulberry, and test its
      ability of quercetin biosynthesis. METHOD: Hairy roots of mulberry were obtained
      through infecting etiolated seedlings with Agrobacterium tumefaciens strain
      C58C1. The culture condition of hairy roots was optimized. The transformation of
      T-DNA was examined by PCR assay and quercetin content was determined by HPLC.
      RESULT: When infecting stem cutting of etiolated seedlings via C58C1 strain, the
      optimal transformation conditions were as follows: 10 minutes' infection, two
      days pre-culture and co-culture, additional hydroxylacetosyringone (As) 100 mg x
      L(-1). The PCR examination result showed that rolB and rolC genes could be
      inserted into the hairy roots of mulberry. Hairy roots appeared in 10 days after
      infecting, the frequency of stems explants was up to 92% after 30 days culturing.
      After 50 days culturing in 1/2MS + 0.05 mg x L(-1) IBA liquid medium, the content
      of quercetin increased by 8. 5-fold. CONCLUSION: Hairy root culture system of
      Moraceae plants was established successfully for the first time. In addition, it
      also provides a foundation for further industrial production of active compounds
      such as quercetin.

PMID- 20822006
TI  - [Improvement of solubility of puerarin through deoxycholate/phospholipid mixed
      micelle preparing technology].
AB  - OBJECTIVE: To prepare puerarin deoxycholate/phospholipid mixed micelle to
      increase the solubility of puerarin. METHOD: Sodium deoxycholate and soybean
      phospholipids were used to prepare puerarin mixed micelle through orthogonal
      design experiments. With the solubility, shape and particle size as the response
      indexes, the preparing process of puerarin mixed micelle was optimized. RESULT:
      The optimized process for the puerarin deoxycholate/phospholipid mixed micelle
      was that the puerarin, soya phosphatidylcholine and sodium deoxycholate with the
      mole ratio of 3:2:4 should be dissolved in methanol-chloroform (1:1), and the
      solvents should be evaporated rotatively at 30 degrees C. The particle diameter
      of the mixed micelle was (64.8 +/- 13) nm (volume-weighted particle size
      distribution), and the solubility was 0.811 1 g x L(-1) in water at the room
      temperature, which was 22.3 times as that of the raw puerarin (0.036 4 g x L-1).
      CONCLUSION: The puerarin deoxycholate/phospholipid mixed micelle can improve the
      solubility of puerarin significantly.

PMID- 20822007
TI  - [Everted intestinal sac method for quick finding absorption ingredients of
      Wuzhuyu decoction].
AB  - OBJECTIVE: To establish a method for quick finding the absorption ingredients of
      Wuzhuyu decoction in order to select the index to control its quality. METHOD:
      The absorption of three concentration of Wuzhuyu decotion was investigated with
      the in vitro-everted intestinal sac model. The intestinal bag fluid of jejunum
      and ileum were collected in different time and the eight ingredients, which were
      evodiamine (Ev), rutaecarpine (Ru), limonin (Li), ginsenoside-Rb1, -Rg1, -Re
      (Rb1, Rg1, Re), isorhamnetin-3-O-beta-D-glucosyl(6''-->1'")-alpha-L-rhamnoside
      (Irs)and 6-gingerol (6-Gi), were detected by HPLC as the represent constituents
      in samples. RESULT: Eight ingredients except Ru in samples could be detected, but
      Ev could not be detected in high concentration samples. The ratios between
      absorption ingredients were different from in Wuzhuyu decotion. CONCLUSION: The
      in vitro-everted intestinal sac canc absorb the ingredients of Wuzhuyu decotion
      selectivity. Compare with the ileum, the jejunum can provide the more absorption
      information and faster, the best test time is 60-90 min.

PMID- 20822008
TI  - [Content detection of bacterial endotoxin in two kinds of injection by gelatin
      technique].
AB  - OBJECTIVE: To detect content of bacterial endotoxin in Yuxingcao and Qingkailing
      injections by specific and nonspecific tachypleus amebocyte lysate technique for
      in order to investigate the feasibility of specific tachypleus amebocyte lysate
      technique for detecting bacterial endotoxin in traditional Chinese drug
      injections. METHOD: Different batches of Yuxingcao and Qingkailing injections
      were detected by specific and nonspecific tachypleus amebocyte lysate kits.
      RESULT: Yuxingcao injection could be detected by specific and nonspecific
      tachypleus amebocyte lysate technique, Whereas Qingkailing injection could be
      detected only by specific tachypleus amebocyte lysate. CONCLUSION: Using specific
      tachypleus amebocyte lysate as a substitute for nonspecific tachypleus amebocyte
      lysate is an effective method for detecting content of bacterial endotoxin in
      Qingkailing injection.

PMID- 20822010
TI  - [Determination of two stilbene glycoside in five processed products of Rheum
      palamatum].
AB  - OBJECTIVE: To compare of the contents of two stilbene glycoside in five processed
      products of Rheum palamatum. METHOD: The contents of trans-3, 5, 4'
      trihydroxystilbene-4'-O-beta-D-glucopyranoside (a) and trans-3, 5, 4'
      trihydroxystilbene-4'-Obeta-D-(6"-O-galloyl)-glucopyranoside (b) were determined
      by HPLC analysis at 35 degrees C with methanol-1% acetic acid as mobile phase,
      the wavelengths were set at 280, 300 nm, the flow rate was 1.0 mL x min(-1).
      RESULT: The two components could be detected in five processed products, and
      their contents were more close in the no-parched pieces, the vinegar roasts
      pieces and the wine roast pieces. However, the contents reduced significantly in
      other two kinds of pieces which were lower than 80 percent of no-parched pieces.
      CONCLUSION: High temperature may result in a significant reduction on glycoside
      in the pieces of rhubarb, and we have received similar results from determination
      of other glycoside compounds. Further analysis and comparison with the content of
      their corresponding aglycones, can provide a scientific basis to explain the
      variation of the material basis in the processed products of rhubarb.

PMID- 20822009
TI  - [Using parallel line assay method based on quantitative responses in methodology
      evaluation for determining lumbrokinase potency in Rongshuan capsules].
AB  - OBJECTIVE: To develop an assay methodology for determination of lumbrukinase
      potency in Rongshuan capsules. METHOD: The agarose-fibrin plate assay methodology
      for determination of Lumbrukinase potency in Rongshuan capsules was studied
      including durability, specificity, linearity range, product's handling method,
      accuracy , repetitiveness, solution stability, recovery and statistical method.
      The method of parallel line assay based on quantitative responses in statistical
      methods for biological assays was used in the statistics of potency assay.
      RESULT: The durability and specificity of assay accord with the requirement; The
      linearity range was 12.5 to approximately 400 U, the RSD of accuracy tests was
      3.2%, the RSD of repetitiveness tests was 8.3%, the solution is stable under 4
      degrees C for 72 hours, the recovery rate was 97.0% and the RSD of recovery
      assays was 16.5%. CONCLUSION: The agar-fibrin plate assay is rapidly, feasible,
      simple, convenient and accurate way for determining the Lumbrukinase potency. The
      method of parallel line assay based on quantitative responses in statistical
      methods for biological assays can control the error of determination.

PMID- 20822011
TI  - [Sapodivarin, a new coumarin from roots of Saposhnikovia divaricata].
AB  - OBJECTIVE: To study the chemical constituents in the dried roots of Saposhnikovia
      divaricata (Turcz.) Schischk. METHOD: The chemical constituents were isolated by
      various column chromatographic methods and structurally elucidated by IR, UV, MS
      and NMR evidences. RESULT: Two compounds were obtained and identified as
      nodakenetin (1) and 8-[4-(beta-D-glucopyrano-sy-loxy)-3-methyl-2-buten-1-yl]oxy-5
      methoxy-6,7-furanocoumarin (2), respectively. CONCLUSION: Compound 2 is a new
      compound and named sapodivarin.

PMID- 20822012
TI  - [Chemical constituents from stem barks of Vernonia cumingiana].
AB  - The chemical constituents from the stem barks of Vernonia cumingiana were
      investigated. Various chromatographic techniques such as silica gel
      chromatography, Sephadex LH-20, ODS column chromatography and HPLC were used to
      isolate and purify the constituents. The structures were elucidated by spectral
      methods. Twelve compounds were isolated from the 95% ethanol extract and their
      structures were elucidated as methyl 3,5-dicaffeoylquinate (1), methyl 3,4
      dicaffeoylquinate (2), ethyl 3,4-dicaffeoylquinate (3), methyl 3,4,5
      tricaffeoylquinate (4), stigmasterol (5), alpha-spinasterol (6), beta-sitosterol
      (7), 24-methylene-lanosta-9 (11)-en-3beta-acetate (8), ethyl gallate (9), di-n
      butyl-phthalate (10), stearic acid (11) and palmitic acid (12). Compounds 1-12
      were isolated from this plant for the first time.

PMID- 20822013
TI  - [Chemical constituents of Acacia catechu].
AB  - OBJECTIVE: To study the chemical constituents of Chinese medicine Acacia catechu.
      METHOD: Isolation and purification were carried out on normal phase silica gel,
      Sephadex LH-20, ODS column chromatography etc. Constituents were identified by
      physicochemical properties and spectral analysis. RESULT: Twelve compounds were
      identified as 4-hydroxybenzoic acid( 1), kaempferol (2), quercetin (3), 3,4',7
      trihydroxyl-3', 5-dimethoxyflavone (4), catechin (5), epicatechin (6), afzelechin
      (7), epiafzelechin (8), mesquitol(9), ophioglonin (10), aromadendrin (11), and
      phenol (12). CONCLUSION: Compounds 7, 12 were isolated from A. catechu for the
      first time, and compounds 4, 9-11 were isolated from the genus Acacia for the
      first time.

PMID- 20822014
TI  - [Chemical constituents from seeds of Paeonia suffruticosa].
AB  - OBJECTIVE: To study the chemical constituents from seeds of Paeonia sufruticosa.
      METHOD: Various chromatographic techniques were used to isolate and purify the
      constituents, their physico-chemical properties and spectral data were employed
      to elucidate their structures. RESULT: Thirteen compounds were isolated and
      identified as: paeoniflorin (1), oxypaeoniflorin (2), 6'-O-beta-D
      glucopyranosylalbiflorin (3), 8-debenzoylpaeoniflorin (4), 8-debenzoylpaeonidanin
      (5), 1-O-beta-D-glucopyranosylpaeonisuf-frone (6), 1-O-beta-D-ethyl
      mannopyranoside (7), sucrose (8), luteolin (9), apigenin (10), benzoic acid (11)
      and 1-0-beta-D-(4-hydroxybenzoyl) glucose (12). CONCLUSION: compounds 2, 4-6 were
      isolated from this plant for the first time, compounds 7 and 12 were isolated
      from the family of Paeoniaceae for the first time.

PMID- 20822015
TI  - [Chemical constituents from leaves of Boehmeria nivea].
AB  - OBJECTIVE: To study the chemical constituents from the leaves of Boehmeria nivea.
      METHOD: The leaves were extracted by 95% EtOH at room temprature, the chemical
      leaves were isolated and purified by repeated silica gel column chromatography,
      Sephadex LH-20 column chromatography and semipreparative HPLC, and their
      structures were identified by physical and chemical properties and spectroscpoic
      methods. RESULT: One compound isolated from n-butanol fraction, four compounds
      were obtained from ethyl acetate fraction and three compounds from petroleum
      ether fraction. Their structures were elucidated as kiwiionoside (1), eugenyl
      beta-rutinoside (2), uracil (3), beta-sitosterol glucoside (4), 3-hydroxy-4
      methoxy-benzoic acid (5), cholesterol (6), alpha-amyrin (7). nonacosanol (8).
      CONCLUSION: Compounds 1-3, 5-8 were isolated from the genus Boehmeria for the
      first time.

PMID- 20822016
TI  - [Chemical constituents of Discocleidion rufescens].
AB  - OBJECTIVE: To study chemical constituents of leaves from Discocleidion rufescens.
      METHOD: Column chromatography and spectroscapic methods were used to isolate and
      identify the constituents. RESULT: Fifteen compounds were isolated and identified
      as chrysophanol (1), physcione (2), taraxerol (3), beta-sitosterol (4),
      daucosterol (5), scopoletin (6), apigenin (7), acacetin-7-O-beta-D-glucoside (8),
      apigenin-7-O-beta-D-glucoside (9 ), luteolin (10), diosmetin-7-O-beta-D-glucoside
      (11), luteolin-7-O-beta-D-glucoside (12), gallic acid (13), amentoflavone (14)
      and myo-inositol (15). CONCLUSION: Compounds 1, 2, 8, 11, 13 and 15 were isolated
      from the genus Discocleidion for the first time.

PMID- 20822017
TI  - [Component analysis and acute hepatotoxicity of volatile oils from argy wormwood
      leaf extracted by different methods].
AB  - OBJECTIVE: To analyze the chemical composition and compare acute hepatotoxicity
      of essential oils extracted from argy wormwood leaf in Guangdong by four
      different methods. METHOD: Four extraction methods, including hydrodistillation
      extraction, supercritical fluid CO2 extraction, petroleum ether ultrasonic
      extraction and petroleum ether microwave extraction, were employed to prepare
      essential oil from argy wormwood leaf in Guangdong. The products were analyzed
      qualitatively and quantitatively using GC-MS and GC-FID. Sixty mice were divided
      into 5 groups according to different essential oils and took the same dose
      orally, then after 5 hours, hepatic functional parameters in serum were detected
      such as alanine aminotransferase (ALT) and so on, and morphologic change of
      hepatic tissues was observed. RESULT: The extraction rate of the four methods and
      identified compounds was 1.02%, 80 (hydrodistillation extraction), 2.46%, 56
      (supercritical fluid CO2 extraction), 3.17%, 45 (petroleum ether ultrasonic
      extraction) and 3.32%, 78 (petroleum ether microwave extraction) respectively.
      Totally 153 compounds were identified from those essential oils. Compared with
      that of the control group, some hepatic functional parameters of
      hydrodistillation and supercritical fluid CO2 extraction groups rose
      significantly (P < 0.01 or P < 0.05), and hepatic tissues of hydrodistillation
      group were damaged significantly. CONCLUSION: The essential oils extracted from
      argy wormwood leaf by different methods may have not only different chemical
      composition, but also different acute hepatotoxicity, and monoterpenes and
      benzenes in the essential oils might induce acute hepatotoxicity.

PMID- 20822018
TI  - [Effects of Shaoqiduogan on MMP-13, TIMP-1 expression in liver and hepatic
      stellate cells of hepatic fibrosis rats].
AB  - OBJECTIVE: To investigate the effects of Shaoqiduogan (SQDG) on the expression of
      matrix metalloproteinase 13 (MMP-13) and tissue inhibitor of metalloproteinase 1
      (TIMP-1) in carbon tetrachloride (CCl4) induced hepatic fibrosis rats and
      transforming growth factor beta1 (TGF-beta1) irritated hepatic stellate cells
      (HSC), and to explore its possible mechanisms. METHOD: The model of chemical
      hepatic fibrosis induced by CCl4 was prepared. The rats were randomly divided
      into 5 groups, including normal control group, liver fibrosis model group and
      SQDG (42. 5, 85, 170 mg x kg(-1)) treated groups. The level of collagen type 1 (C
      1) in serum was determined by radioimmunoassay. Masson stain was used to examine
      the histopathological change. MMP-13 and TIMP-1 ex-pression in liver tissues were
      assayed by immunohistochemistry. In vitro, effects of SQDG on the expression of
      MMP-13, TIMP-1 and C-1 in HSC-T6 stimulated by TGF-beta were measured by Western
      blot. RESULT: The results showed that SQDG significantly decreased the elevated
      level of C-1 in serum of hepatic fibrosis rats induced by CCl4. Pathological
      examination showed that SQDG could remarkably alleviate the degree of liver
      fibrogenesis and formation of pseudolobulus. The results of immunohistochemistry
      demonstrated that SQDG significantly increased MMP-13 expression and decreased
      TIMP-1 expression in liver tissues. Furthermore, SQDG (20-160 mg x L(-1)) could
      facilitate MMP-13 expression, inhibit TIMP-1 expression and significantly inhibit
      the C-I production of HSC stimulated with TGF-beta1 in vitro. CONCLUSION: The
      anti-fibrotic effects of SQDG may be associated with its action of promoting
      collagen degradation via controlling the levels of MMP-13 and TIMP-1 in liver.

PMID- 20822019
TI  - [Effects of Baixiangdan capsule on location and expression levels of GABA(A)
      receptor beta2 subunit in hippocampus of PMS model rats with liver-qi invasion].
AB  - OBJECTIVE: To explore the effects of Baixiangdan capsule(BXD), a Chinese herbal
      compound, on the location and expression levels of GABA(A) receptor beta2 subunit
      (GABA(A)Rbeta2) in hippocampus of PMS model rats with liver-qi invasion. METHOD:
      After vaginal smear examination and open field test, the selected SD rats were
      randomly divided into 3 groups Normal group, PMS model group with liver-qi
      invasion and PMS BXD-administration group with liver-qi invasion (BXD was
      administered with oral dosage of 10 g x kg(-1) body weight every day for 5 days).
      PMS model rats with liver-qi invasion were induced by electric stimulating, and
      evaluated by macro-behavior observation and open-field test. The location and
      expression of GABA(A) receptor in hippocampus were measured by fluorescence
      microscopy and western blot respectively. RESULT: Compared with the normal group,
      the open field scores and GABA(A) Rbeta2 expression of PMS model rats with liver
      qi invasion were increased significantly, and the distribution of GABA(A)
      receptor is more concentrated. However, the scores and GABA(A) beta2 expression
      of PMS BXD-administration group with liver-qi invasion were decreased markedly.
      Compared with the PMS model group the location had no significant change.
      CONCLUSION: One of micro-mechanisms of PMS model rats with liver-qi invasion may
      be related with the high expression of GABA(A) Receptor beta2 subunit in
      hippocampus, and the Chinese medicinal formula, BXD granule, had an adjust on the
      above abnormal changes.

PMID- 20822020
TI  - [Effects of Yinqiao detoxifcation oral liquid on NK cell viability and serum
      concentration of IFN-gamma in SCID mouse infected by influenza virus FM1].
AB  - OBJECTIVE: To explore the dynamic effects of Yinqiao detoxifcation oral liquid
      (YQD) on NK cell lysis in spleen and serum concentration of IFN-gamma in SCID
      mouse infected by influenza A virus FM1. METHOD: The mice were divided into six
      different groups randomly. Except normal control, other mice were intranasally
      instilled with 15 TCID of virus. Three dosage groups of YQD (5.0, 10.0, 20.0 g x
      kg(-1)) were respectively fed with YQD. Positive control group was administrated
      orally with 0.07 g x kg(-1) of ribavirin. Normal control and model group were fed
      with physiological saline. After 1, 3, 5 and 7 days' infection, spleens and serum
      were collected. Then the NK cell lysis was detected by LDH release kit and the
      concentration of IFN-gamma was examined by ELISA assay. RESULT: Contents of IFN
      gamma reached to peak value on the 3th day and until the 5th day. Later, the
      level of IFN-gamma returned to normal level. The variation tendency of activity
      of NK cell in spleen was according with that of IFN-gamma. But it reached the
      maximum value until the 5th day. The activity of NK cell lysis in three groups of
      YQD was well above that i n model group. In addition, therapeutic action of both
      10.0 g x kg(-1) and 20.0 g x kg(-1) of YQD treatment groups was better than that
      of 5.0 g x kg(-1). CONCLUSION: The data showed that serum concentration of IFN
      gamma and NK cell lysis were improved by YQD at different time, which was
      demonstrated YQD could perform well in immune system.

PMID- 20822021
TI  - [Preventive effects of multi-glycoside of Tripterygium wilfordii on glomerular
      lesions in experimental diabetic nephropathy].
AB  - OBJECTIVE: To observe the preventive effects of multi-glycoside of Tripterygium
      wilfordii (GTW) on glomerular lesions in experimental diabetic nephropathy (DN).
      METHOD: The DN model of rats was established with streptozotocin (STZ) and
      intervened with GTW. In the same time, normal, benazepril, and vehicle control
      groups were set up. After 8 weeks of oral treatment with GTW (50 mg x kg(-1) BW),
      benazepril (6 mg x kg(-1) BW), and vehicle (physiological saline), the changes of
      body weight, urine albumin (UA1b), blood glucose (BG), serum creatinine (Scr),
      blood urea nitrogen (BUN) and glomerular morphology were examined. In addition,
      the level of protein expression of alpha-smooth muscle actin (alpha-SMA) and
      collagen type I in glomeruli was determined by immunofluorescence. RESULT: Both
      GTW and benazepril reduced UA1b. GTW ameliorated glomerular injury, such as
      mesangial cell proliferation, alpha-SMA and collagen type I over-expression, in
      DN model. Compared with benazepril, beneficial effects of GTW on
      glomerulusclerosis were more significant (total cell number: GTW group 54.44 +/-
      2.41, benazepril group microg/67.83 +/- 4.41, P < 0.05; alpha-SMA score: GTW
      group 1.98 +/- 0.52, benazepril group 2.27 +/- 0.46, P < 0.05; collagen type I
      score: GTW group 2.11 +/- 0.37, benazepril group 2.88 +/- 0.58, P < 0.05).
      CONCLUSION: Preventive effects of GTW on glomerular lesion in DN model are
      related to decreasing UA1b and ameliorating glomerulusclerosis.

PMID- 20822022
TI  - [Effect of polysaccharides in processed Sibiraea on immunologic function of
      immunosuppression mice].
AB  - OBJECTIVE: To study the effect of polysaccharides in processed Sibiraea on the
      immunologic function of immunosuppression mice. METHOD: The immunosuppressed mice
      were induced by cyclophosphamide. After the treatment, the organ weight index and
      the delayed type hypersensitivity of the mice were investigated. The humoral
      immune function was determined by serum hemolysin assay. Non-specific immune
      function was determined by carbon clearance method. Cellular immune function was
      determined by spleen lymphocyte proliferation test. Two hundred kunming mice were
      randomly divided into five groups: normal controls, model group, low-dose group
      (110 mg x kg(-1)), middle-dose group (220 mg x kg(-1)), high-dose group (440 mg x
      kg(-1)). Drugs were given to the mice by oral gavage every day. RESULT: The
      immunosuppressed mice treated with Sibiraea polysibcharide at intragastrica dose
      of 110-440 mg x kg(-1) have increased weight of the immune organs, increased
      content of DTH and content in serum hemolysin lgG and lgM. Mean while the rate of
      carbon clearance was enhanced and the proliferation of spleen lymphocyte was
      increased. CONCLUSION: Polysaccharides in processed Sibiraea can increase the
      weight of the immune organs. At the same time, non-specific immune, DTH, humoral
      immune and cellular immune function were enhanced significantly.

PMID- 20822023
TI  - [Hepatic energy metabolism on rats by six traditional Chinese medicine with hot
      property].
AB  - OBJECTIVE: To investigate the common rule of hepatic energy metabolism on rats by
      six traditional Chinese medicine (TCM) with hot property. METHOD: The activity of
      Na(+)-K(+)-ATPase, Ca2(+)-ATPase and succinate hydrogenase (SDH), the content of
      hepatic glycogen and the mRNA expression of hepatic uncoupling protein2 (UCP2)
      were measured after the rats were administrated with water extracts of Radix
      Aconiti Lateralis Preparata, Rhizoma Zingiberis, Rhizoma Alpiniae Officinarum,
      Pericarpium Zanthoxyli and Cortex Cinnamomi, Fructus Evodiae at the dose of 10.5,
      8.4, 6.0, 4.0, 3.5, 4.2 g x kg(-1). respectively in 30 days, twice a day. RESULT:
      The activity of Na+(-)K(+)-ATPase has been increased by the six TCM and the
      statistical significance has been observed in Rhizoma Alpiniae Officinarum,
      Pericarpium Zanthoxyli, Fructus Evodiae groups. The raising tendency of Ca2(+)
      ATPase activity has been observed by the six TCM and the statistical significance
      has been obtained in Rhizoma Alpiniae Officinarum group. The activity of SDH has
      been increaseded by six TCM while statistical significance has been observed
      except in five groups of the six groups except in Radix Aconiti Lateralis
      Preparata group. The content of hepatic glycogen has been decreased significantly
      by six TCM. No signiticant change of the mRNA expression of UCP2 has been found.
      CONCLUSION: TCM has good effects on hepatic energy metabolism by raising the
      activity of mitochondria SDH to increase the production of ATP and by increasing
      the activity of Na(+)-K+)-ATPase, Ca2(+)-ATPase to increase the consumption of
      ATP.

PMID- 20822024
TI  - [Effects of berberine on serum levels of inflammatory factors and inflammatory
      signaling pathway in obese mice induced by high fat diet].
AB  - OBJECTIVE: To investigate the effect of berberine on serum levels of TNF-alpha,
      IL-6 and adiponectin in obese mice induced by high fat diet and its potential
      molecular mechanisms. METHOD: Normal male Kunming mice were randomly divided into
      two groups taking normal chow (NC, n = 10) and high fat diet (HF, n = 30),
      respectively. After 13 weeks, HF mice were continuously given high fat diet and
      divided into three groups, model group (BM), low-dosage of berberine group (BL)
      and high-dosage of berberine group (BH). Mice in BL and BH were administered
      berberine by gavage at the dosage of 50 mg x kg(-1) and 150 mg x kg(-1),
      respectively. Two weeks later, oral glucose tolerance test was performed. At the
      end of the experiment, the mice were killed and blood samples were collected. The
      epididymal fat tissue and liver were removed promptly and weighed. The serum
      cytokine was measured by ELISA. The levels of IkappaB kinase beta (IKK-beta) and
      IKK-beta (ser181) were detected by Western blotting. RESULT: Serum levels of TNF
      alpha, IL-6 in mice of BM were significantly higher than those in NC (P < 0.05).
      After two-week treatment of berberine, serum levels of TNF-alpha, IL-6 in BL and
      BH were lower than those in BM (P < 0.05, respectively). However, there were no
      significant difference of adiponectin among four groups. The degrees of
      phosphorylation of IKK-beta (ser181) were decreased in liver and adipose tissue
      in BH in comparison to that in BM, although the expression of total IKK-beta did
      not change. Furthermore, the glucose tolerance was improved, while the body
      weight and epididymal fat were reduced in mice treated with berebrine. 9:
      Berberine is able to reduce inflammatory cytokines expression and inhibit
      activation of IKK-beta (ser181) in obese mice, which may partly explain the
      therapeutic effect of berberine on insulin resistance and abnormal glucose
      metabolism.

PMID- 20822025
TI  - [Transmembrane transport activity of paclitaxel regulated by fangchinoline in
      MDR1-mDCK II cells].
AB  - OBJECTIVE: To research the regulation of transmembrane transport activity of
      paclitaxel influenced by fangchinoline in MDR1-MDCK II cells. METHOD: Paclitaxel,
      one of the substrate of P-gp, was selected as the model drug. Verapamil
      hydrochloride was adopted as the active control to investigate the bilateral
      transport activity of paclitaxel regulated by fangchinoline in MDR1-MDCK II
      cells. RP-HPLC was applied to determine the concentration of paclitaxel in the
      transporting medium, which was used to calculate apparent permeability
      coefficient of paclitaxel across MDR1-MDCK I1 monolayer cells. RESULT: The efflux
      rate of paclitaxel was faster than the absorption rates across the MDR1-MDCK II
      monolayer cells with highly expressed P-gp. The absorption rates of paclitaxel
      combinated with fangchinoline and verapamil hydrochloride respectively were
      remarkably increased and the efflux rate was decreased. The reversal effect of
      the fangchinoline was stronger than the verapamil hydrochloride with the same
      molar concention. CONCLUSION: Fangchinoline can apparently decrease the efflux of
      paclitaxel and inhibit the multidrug resistance of antitumor drug mediated by P
      gp.

PMID- 20822026
TI  - [Protective effects of asiaticoside on sepsis-induced acute kidney injury in
      mice].
AB  - OBJECTIVE: The present study is to investigate the protective effects of
      asiaticoside on sepsis-induced acute kidney injury in mice. METHOD: With the
      sepsis induced by cecal ligation and puncture (CLP), forty eight kunming mice
      were randomly divided into four groups as sham operated, CLP treated, CLP +
      asiaticoside 15, 45 mg x kg(-1) groups. General conditions and the amount of dead
      rate of mice were observed. The BUN and Cr levels were observed by the kits. IL-6
      in serum was assayed by enzyme-linked immunosorbent assay (ELISA). Kidney tissues
      were harvested for determination of iNOS expression by Western blotting analysis.
      The pathologic changes were observed under electron microscope via hematoxylin
      eosin (HE) stain. RESULT: Compared with CLP group, the death rate, the levels of
      BUN, Cr, IL-6, and iNOS protein expression of asiaticoside groups were
      significantly reduced. The pathologic changes in kidney tissues induced by sepsis
      were significantly attenuated dose-dependently by asiaticoside under electron
      microscope. CONCLUSION: Asiaticoside has protective effects against sepsis
      induced acute kidney injury, which were probably associated with the inhibition
      of IL-6 in serum and iNOS protein in kidney tissues.

PMID- 20822027
TI  - [Cytokine changes in community-acquired pneumonia in elderly and intervention of
      traditional Chinese medicine].
AB  - OBJECTIVE: To make a study of the cytokine changes in community-acquired
      pneumonia (CAP) in the elderly and the intervention of traditional Chinese
      medicine that can clear away the lung-heat and dissipate blood stasis
      (Qingfeihuayu soup). METHOD: The 82 cases with CAP in the elderly were divided at
      random into two treatment group and control group. Based on heteropathy, the
      treatment group was given Qingfeihuayu soup two times a day. The control group
      was given Rocephin 2 g once daily for 7 days. The clinical effect and the changes
      in TNF-alpha, IL-6 and IL-10 were observed before and after the treatment. A
      healthy group was also set up. RESULT: Before treatment, IL-6 and TNF-alpha in
      both groups were higher than the healthy group (P < 0.01) and IL-10 lower than
      the healthy group (P < 0.01). After treatment, IL-6 and TNF-alpha in both groups
      decreased (P < 0.01) while IL-10 in treatment group increased. There existed a
      great difference compared with the control group (P < 0.01). The total effective
      rate in the treatment group is 92.50% while the control group is 85.71%. thus
      have a great difference (P < 0.05). CONCLUSION: During the process of the
      development of CAP in the elderly, there existed the phenomenon of the excessive
      release of TNF-alpha, IL-6 and the too much inhibition of IL-10. The unbalance of
      TNF-alpha, IL-6, IL-10 can be a monitoring index reflecting the severity of the
      disease. The Chinese medicine Qingfeihuayu soup has obviously have regulating and
      clinical effect.

PMID- 20822028
TI  - [Advanced achievements about neuroprotective mechanisms of paeoniflorin].
AB  - Paeoniflorin is one of the bioactive components of Paeonia lactiflora, a
      traditional Chinese herbal medicine. Some recent studies prove its distinguished
      neuroprotective effect. These neuroprotective mechanisms have become hot points
      and show closely correlated to activating adenosine A1 receptor, ameliorating the
      function of cholinergic nerve, regulating ion channel homeostasis, retarding
      oxidative stress and apoptosis of the neurocytes, promoting nerve growth, having
      an influence on astrocytes and being ableto penetrate though blood brain barrier.
      In this review, we present the neuroprotective mechanisms of paeoniflorin in the
      following eight aspects.

PMID- 20822029
TI  - [A discussion of key issues on postmarketing reevaluation of Chinese medicine].
AB  - Because of relatively simple purposes, narrow population range, small samples,
      stringent controlled conditions for using medicine, and short time of clinical
      trials, the researches for listing approval of Chinese medicine can not draw to
      comprehensive conclusions on safety and effectivenes, which is not conducive to
      the reasonable and safe application of postmarketing Chinese medicine. Safety
      reevaluation is the most important issue of the postmarketing reevaluation of
      Chinese medicine, including adverse reaction/ incidence reporting, monitoring and
      evaluation three aspects, which must be taken into action with strict regulatory
      measures. Effectiveness reevaluation is still an important part of the
      postmarketing reevaluation of Chinese medicine, including reevaluation of
      diseases and syndromes adapted for using Chinese medicine, precise doses and
      appropriate treatment periods, which is an important prerequisite to ensure the
      safety of using Chinese medicine. At the same time, we should pay attention to
      the safety and effectivenes of Chinese medicine on special populations, attach
      great importance to postmarketing reevaluation of Chinese medicine injection, and
      apply appropriate research methods to carry out reevaluation studies. National
      drug administrative departments must strengthen management and supervision on
      postmarketing Chinese medicine, develop and improve policies, regulations and
      technical standards on the reevaluation, forming a legal basis for carrying out
      postmarketing reevaluation of Chinese medicine.

PMID- 20822030
TI  - [Postmarketing herbs clinical evaluation should concern about re-evaluating
      symptoms].
AB  - Re-evaluation of premarketing medicine is a important supplementary of clinical
      and elementary research. It is a basement that establish the medicine
      administration supervisition , found and integrity postmarketing washing out
      mechanism and define reasonable using drug. After drug marketing, we must not
      only concern on the re-evaluation of herbs security but also focus on evaluating
      herbs suitable symptom, as well as its dosage and course of treatment, ect. The
      re-evaluation of symptoms were seen as the core and feature of traditional
      Chinese medicine's clinical evaluation. It is also seen as hot spot and
      difficulty of the research . This article try to focus on simply illustrating the
      necessity and research thinking of re-evaluation symptoms of postmarketing herbs.
      So we can define the re-evaluation of postmarketing drug's objection, method, and
      basement. It will provide beneficial experience and reference to re-evaluation
      symptom of marketed herbs.

PMID- 20822031
TI  - Legal. Protect your procurement.

PMID- 20822032
TI  - Dermatologic toxicities of targeted anticancer therapies.
AB  - The discovery of the intricate intracellular signaling networks that regulate
      normal cellular proliferation and survival but can also drive the oncogenic
      process when aberrantly activated has led to the emergence of targeted agents in
      oncology. The introduction of such agents has resulted in improved survival and
      more tolerable treatments, reducing systemic toxicities such as myelosuppression.
      Nevertheless, it has become evident that these agents are associated with a wide
      spectrum of dermatologic toxicities that often manifest in cosmetically sensitive
      areas and may affect the majority of patients. Associated pain and pruritus can
      negatively impact quality of life, resulting in dose modification or treatment
      interruptions that interfere with potentially life-prolonging therapy. Extensive
      efforts throughout the past decade have concentrated on describing the
      clinicohistopathologic characteristics, elucidating the underlying mechanisms,
      and investigating potential management strategies. Currently, however, proposed
      treatment guidelines arise from expert opinions, anecdotal evidence, and few data
      from clinical trials. This article reviews the spectrum of dermatologic
      toxicities associated with a variety of targeted agents used alone or in
      combination with other modalities, delineating their clinical presentation,
      underlying mechanisms, and management options.

PMID- 20822033
TI  - Rash from newer cancer agents: why do we still not have effective therapy for
      palliation and/or prevention?

PMID- 20822034
TI  - Mechanisms of fatigue.
AB  - Fatigue is a common experience of individuals suffering from chronic illnesses.
      Mechanisms responsible for fatigue may be central or peripheral. Central fatigue
      may result from proximal events and include the neuromuscular junction and are
      subdivided into spinal and supraspinal. Peripheral fatigue arises from the muscle
      and predominately involves muscle bioenergetics or excitation contraction.
      Fatigue from chronic illnesses can be caused by several mechanisms.
      Electromyelography, transcranial magnetic stimulation, magnetic resonance
      imaging, and spectroscopy are helpful tools to clarify the physiologic correlates
      of fatigue. This state-of-the-art review discusses these physiologic correlates
      of fatigue and the mechanisms described in a variety of chronic diseases.

PMID- 20822035
TI  - Cancer-related fatigue: a multidimensional syndrome.

PMID- 20822036
TI  - The underrecognized role of impaired muscle function in cancer-related fatigue.

PMID- 20822037
TI  - Symptom control in stem cell transplantation: a multidisciplinary palliative care
      team approach. Part 2: psychosocial concerns.
AB  - Stem cell transplantation (SCT) offers a potential cure for patients with
      otherwise incurable benign and malignant disorders. However, the treatment will
      cause considerable physical, social, psychological, and spiritual suffering. In
      part 1 of this review, the management of the physical symptoms was reviewed. In
      part 2, we discuss the approaches to managing the other aspects of distress that
      are primarily psychological, social, and spiritual in nature. In practice, these
      dimensions are not so easily distinguished; the division between physical and
      psychological symptoms is blurred, and physical symptoms are often interrelated
      with the patient's emotional status and social support.

PMID- 20822039
TI  - [Letters].

PMID- 20822038
TI  - Fentanyl pectin nasal spray in breakthrough cancer pain.
AB  - Abstract Fentanyl pectin nasal spray (FPNS) is being developed to improve
      analgesic onset, treatment efficacy, and satisfaction/acceptability in treating
      breakthrough cancer pain (BTCP). Patients (n = 114) were entered into a
      randomized, placebo-controlled, double-blind, multicenter study. Patients who
      successfully titrated (n = 83) entered a double-blind phase; 10 episodes of BTCP
      were treated with the effective dose (7) or placebo (3). Pain intensity (11-point
      scale) and pain relief (5-point scale) were assessed between 5 and 60 minutes.
      Use of rescue medications was recorded, and acceptability assessments were
      conducted 30 and 60 minutes post dose. Only 6% of patients failed to titrate to
      an effective dose of FPNS due to lack of efficacy and 5% due to adverse events. A
      total of 91% of randomized patients completed the study. Episode analysis (FPNS,
      n = 459; placebo, n = 200) revealed that compared with placebo, 33% of FPNS
      episodes showed an onset of improvement in pain intensity at 5 minutes (P <
      0.05); 33% of episodes by 10 minutes had clinically meaningful pain relief (> or
      = 2 point decrease in pain intensity; P < 0.0001). Satisfaction with the
      convenience and ease of use of FPNS was reported by 70% and 68% of patients,
      respectively; 87% of patients elected to continue treatment post study. FPNS
      provided rapid analgesia in BTCP and was well accepted by patients.

PMID- 20822040
TI  - Aspects of the epidemiology, research, and control of lentiviral infections of
      small ruminants and their relevance to Dutch sheep and goat farming.
AB  - In 1862, the veterinarian Loman reported the first sheep in The Netherlands with
      symptoms associated with lentiviral infection, although at the time the symptoms
      were ascribed to ovine progressive pneumonia. In the following century, similar
      cases were reported by South African, French, American, and Icelandic
      researchers. Extensive research into the pathology, aetiology, and epidemiology
      of this slowly progressive and ultimately fatal disease was initiated in several
      countries, including the Netherlands. Studies of the causative agents--maedi
      visna virus (MVV) in sheep and caprine arthritis encephalitis virus (CAEV) in
      goats, comprising the heterogeneous group of the small ruminant lentiviruses
      (SRLV)--prompted the development of diagnostic methods and the initiation of
      disease control programmes in many European countries including the Netherlands,
      as a pioneer in 1982, and in the U.S.A. and Canada.

PMID- 20822041
TI  - [Who the bottom of the can wants...].

PMID- 20822042
TI  - [MRSA-positive horses are not necessarily carriers].

PMID- 20822043
TI  - [Frauke Ohl, speaker at the KNMVD congress].

PMID- 20822044
TI  - [Ethics in the practice: a lame collie, reason for euthanasia?].

PMID- 20822045
TI  - [Feline caliciviruses, the feline disease complex amd retrovirus infections in
      the cat].

PMID- 20822046
TI  - [Quality needs to be tested].

PMID- 20822047
TI  - [Vetcis is more than just a database].

PMID- 20822048
TI  - [Third Boehringer Ingelheim 'expert forum' about animal welfare in farm animals].

PMID- 20822049
TI  - [Happy hour with Aart Vierhouten at the Rhederoord Estate].

PMID- 20822050
TI  - [Preparticipation sports screening: state of affairs].

PMID- 20822051
TI  - [What's new after an ACL tear?].
AB  - Following a severe knee sprain during which the anterior cruciate ligament has
      been torn, the patient and his doctor are facing the choice between a
      conservative treatment or a surgical approach. Reviewing the international
      literature allows us to build a pertinent opinion. If the conservative treatment
      is selected, one must be aware that the proportion of good results does not
      exceed 50%. This is why, this treatment is only recommended for little demanding
      and non-sports active persons. In various surgical options, the autologous
      anterior cruciate ligament reconstruction, using a graft of patellar or
      hamstrings tendons gives good, reliable and reproducible results.

PMID- 20822052
TI  - [Overuse injuries of the hip in adolescents].
AB  - Painful femoro-acetabular impingement symptoms localized in the groin in flexion,
      adduction and internal rotation can be explained either by a primary disease of
      the labrum often post-traumatic, and more frequently as part of femoro-acetabular
      primary or secondary dysmorphia. The kinematic of the normal hip joint depends of
      peri-acetabular structures, geometry of joints and possible pathologies that
      could contribute to modify either the geometry or the proprioceptive function. By
      combining and analyzing these parameters it is possible to describe a joint
      concept of centricity, an essential parameter for optimal functions of the joint.
      The concept of overload is explained as the inability of the hip to ensure its
      centricity during activities that could lead to the occurrence of any
      degenerative disorders.

PMID- 20822053
TI  - [Physical activity behavior in the Swiss population: what do we know in 2010?].
AB  - Since 1999 Switzerland has physical activity recommendations for adults, since
      2006 also for school-age children and adolescents. The best available estimates
      indicate that 32% of adults meet the recommendations for three endurance-type
      training sessions and another 9% the minimal recommendations of half an hour
      moderate intensity physical activity on most days of the week. 13% of adolescents
      seem to meet the minimal recommendations of one hour on every day of the week,
      35% on five days per week. All approaches for physical activity promotion are
      very important, with the medical care settings having a particular role in
      reaching inactive individuals.

PMID- 20822054
TI  - [Benefits of physical activity].
AB  - With the evolution of the development of knowledge and progress in automatic
      technologies, the human society gradually turned into a sedentary population. It
      is moreover clearly established that the physical activity is insufficient in
      Europe and in the developed countries. The physical activity is certainly
      beneficial for many reasons, but it is especially the inactivity which is
      dangerous. To date, many scientific publications showed the benefits of the
      physical activity as well in the treatment of chronic diseases as in the
      prevention of those diseases. The objective of this article is, on the one hand,
      to show the concrete influence of the physical activity as a treatment, and on
      the other hand to briefly review its impact on different systems of the human
      organism.

PMID- 20822055
TI  - [Upper respiratory tract infections and sports].
AB  - Upper respiratory tract infections are frequent in athletes. Mainly of viral
      origin, they are treated symptomatically. Infectious mononucleosis is associated
      with an estimated 2% per hundred risk of splenic rupture, which occurs between
      day four and twenty one of the illness. Therefore return to play guidelines
      recommend avoiding, exercice during the first twenty one days. Physical exercise
      seems to influence the immune system, depending on the intensity and length of
      it. But the relationship between physical exercise and risk of infections remains
      controversial: some articles showing an increase in risk, whereas others
      suggesting a certain degree of protection, in athletes. The actual generally
      accepted working theory is the J-curve proposed by Nieman. This model remains to
      be formally proven.

PMID- 20822056
TI  - [Physiotherapy and osteopathy: a real holistic supervision of athletes].
AB  - The medical and paramedical supervison of sportsmen and sportwomen require an
      excellent collaboration and the recognition of the competencies of each person
      among the sport medical team. Physiotherapy and osteopathy are complementary and
      indissociable activities in this framework. The practitioner with this double
      education could provide real holistic care with efficient, safe and evidence
      based methods in cases of traumatic or overload pathologies as well as in cases
      of functional disorders. This will be illustrated with a clinical observation.

PMID- 20822057
TI  - [The biopsychosocial model: much more than additional empathy].
AB  - Despite several limits, the biopsychosocial model is the best available medical
      model today. However, it is still misunderstood and underused. On a theoretical
      point of view, this system of health-explanatory hypotheses considers biological,
      psychological and social factors on equal grounds, in a complex, multiple and
      circular system of causes and effects. A clinical practice derived from this
      model permanently integrates the biological, psychological and social
      perspectives. It necessitates active participation of the patient and stresses
      the importance of educational aspects. The therapeutic relationship is deeply
      modified. A better diffusion of the biopsychosocial model necessitates changes in
      teaching, research and increased resources allocated to the clinical encounter.

PMID- 20822058
TI  - [The Summer, the dizzy spell of Anna and the World Cup of soccer].

PMID- 20822059
TI  - [Recidivism of sex offenses: what can be done? (3)].

PMID- 20822060
TI  - [Premenstrual syndrome and serotonin reuptake inhibitors].

PMID- 20822062
TI  - [The optimism (forced) of global thought].

PMID- 20822061
TI  - [Normality of the libido (andropause)? (4)].

PMID- 20822063
TI  - Free preventive services make sense--up to a point.

PMID- 20822064
TI  - Despite downturn, pharmacy jobs abound.

PMID- 20822065
TI  - Lessons learned in building the patient-centered medical home.

PMID- 20822066
TI  - Drug pipeline loses pressure.

PMID- 20822067
TI  - Health plans prepare to meet challenges of climate change.

PMID- 20822068
TI  - The forces that feed medical travel.

PMID- 20822069
TI  - Medicare's new head--and what he's said.

PMID- 20822070
TI  - Public deserves honest debate on rationing.

PMID- 20822071
TI  - Cost-sharing effects on adherence and persistence for second-generation
      antipsychotics in commercially insured patients.
AB  - PURPOSE: To assess the relationship between patient cost-sharing (e.g.,
      copayments or coinsurance) and adherence and persistence to second-generation
      (atypical) antipsychotic (SGA) medications. DESIGN AND METHODOLOGY: A
      retrospective, observational study of adults aged 18-64 years with schizophrenia
      or bipolar disorder (n = 7,910) who initiated SGA medications with employer
      sponsored insurance in the 2003-2006 MarketScan Commercial Claims and Encounters
      Database. Adherence was defined as percent of days covered in each calendar
      quarter. Persistence was defined as days from initiation of SGA to the first 90
      day gap in medication on-hand. Generalized Estimating Equations were used to
      determine the effects of cost-sharing on adherence to SGA medications based on
      patient-quarter data. A Cox proportional hazards model with patient cost-sharing
      as a time-varying covariate estimated the effects on persistence with SGA
      medication. PRINCIPAL FINDINGS: Higher cost-sharing was associated with a lower
      likelihood of adherence. When compared to plans with cost-sharing below $10,
      adherence rates were approximately 27% lower for patients in plans with SGA cost
      sharing of $50 and above and about 10% lower for patients in plans with cost
      sharing between $30 and $50. In both cases, the reduction in adherence was
      significant. Higher cost-sharing was also associated with a shorter time to
      discontinuation (HR: 1.028; 95% CI [1.006-1.051]). CONCLUSION: High SGA cost
      sharing appears to be a financial barrier to SGA medication compliance,
      especially when cost-sharing levels exceeded $30. Our findings have implications
      for health plans, employers, and policymakers who have, or are, contemplating
      establishing cost-sharing tiers for SCA medications for commercially insured
      patients with serious mental illnesses.

PMID- 20822072
TI  - Who pays more for second- and third-tier drugs?

PMID- 20822073
TI  - Avoiding infusion therapy prime benefit of new MS drug.

PMID- 20822074
TI  - Massachusetts medical home made for Medicaid.

PMID- 20822075
TI  - Kids' health coverage a continuing bright spot.

PMID- 20822076
TI  - Do pacifiers reduce the risk of sudden infant death syndrome?

PMID- 20822077
TI  - Are hypotonic maintenance fluids safe in hospitalized children?

PMID- 20822078
TI  - Hyperlipidemia treatment in children: the younger, the better.

PMID- 20822079
TI  - Screening for hyperlipidemia in children: primum non nocere.

PMID- 20822081
TI  - Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation.

PMID- 20822082
TI  - Anemia in older persons.
AB  - Anemia in older persons is commonly overlooked despite mounting evidence that low
      hemoglobin levels are a significant marker of physiologic decline. Using the
      World Health Organization definition of anemia (hemoglobin level less than 13 g
      per dL [130 g per L] in men and less than 12 g per dL [120 g per L] in women),
      more than 10 percent of persons older than 65 years are anemic. The prevalence
      increases with age, approaching 50 percent in chronically ill patients living in
      nursing homes. There is increasing evidence that even mild anemia is associated
      with increased morbidity and mortality. Anemia warrants evaluation in all older
      persons, except those at the end of life or who decline interventions. About one
      third of persons have anemia secondary to a nutritional deficiency, one third
      have anemia caused by chronic inflammation or chronic kidney disease, and one
      third have unexplained anemia. Nutritional anemia is effectively treated with
      vitamin or iron replacement. Iron deficiency anemia often is caused by
      gastrointestinal bleeding and requires further investigation in most patients.
      Anemia of chronic inflammation or chronic kidney disease may respond to treatment
      of the underlying disease and selective use of erythropoiesis-stimulating agents.
      The treatment of unexplained anemia is difficult, and there is little evidence
      that treatment decreases morbidity and mortality, or improves quality of life.
      Occasionally, anemia may be caused by less common but potentially treatable
      conditions, such as autoimmune hemolytic anemia, malignancy, or myelodysplastic
      syndrome.

PMID- 20822083
TI  - Health effects of prenatal radiation exposure.
AB  - Pregnant women are at risk of exposure to nonionizing and ionizing radiation
      resulting from necessary medical procedures, workplace exposure, and diagnostic
      or therapeutic interventions before the pregnancy is known. Nonionizing radiation
      includes microwave, ultrasound, radio frequency, and electromagnetic waves. In
      utero exposure to nonionizing radiation is not associated with significant risks;
      therefore, ultrasonography is safe to perform during pregnancy. Ionizing
      radiation includes particles and electromagnetic radiation (e.g., gamma rays, x
      rays). In utero exposure to ionizing radiation can be teratogenic, carcinogenic,
      or mutagenic. The effects are directly related to the level of exposure and stage
      of fetal development. The fetus is most susceptible to radiation during
      organogenesis (two to seven weeks after conception) and in the early fetal period
      (eight to 15 weeks after conception). Noncancer health effects have not been
      detected at any stage of gestation after exposure to ionizing radiation of less
      than 0.05 Gy (5 rad). Spontaneous abortion, growth restriction, and mental
      retardation may occur at higher exposure levels. The risk of cancer is increased
      regardless of the dose. When an exposure to ionizing radiation occurs, the total
      fetal radiation dose should be estimated and the mother counseled about the
      potential risks so that she can make informed decisions about her pregnancy
      management.

PMID- 20822084
TI  - Radiation exposure during pregnancy.

PMID- 20822085
TI  - Neuropsychological evaluation in primary care.
AB  - Referring a patient to a neuropsychologist for evaluation provides a level of
      rigorous assessment of brain function that often cannot be obtained in other
      ways. The neuropsychologist integrates information from the patient's medical
      history, laboratory tests, and imaging studies; an in-depth interview; collateral
      information from the family and other sources; and standardized assessment
      instruments to draw conclusions about diagnosis, prognosis, and response to
      therapy. Family physicians can use this information in the diagnosis and
      treatment of patients with depression, dementia, concussion, and similar
      conditions, as well as to address concerns about decision-making capacity.
      Certain assessment instruments, such as the Mini-Mental State Examination and
      Patient Health Questionnaire-9, are readily available and easily performed in a
      primary care office. Distinguishing among depression, dementia, and other
      conditions can be challenging, and consultation with a neuropsychologist at this
      level can be diagnostic and therapeutic. The neuropsychologist typically helps
      the patient, family, and primary care team by establishing decision-making
      capacity; determining driving safety; identifying traumatic brain injury
      deficits; distinguishing dementia from depression and other conditions; and
      detecting malingering. Neuropsychologists use a structured set of therapeutic
      activities to improve a patient's ability to think, use judgment, and make
      decisions (cognitive rehabilitation). Repeat neuropsychological evaluation can be
      invaluable in monitoring progression and treatment effects.

PMID- 20822086
TI  - Osteoporosis in men.
AB  - Osteoporosis is an important and often overlooked problem in men. Although the
      lifetime risk of hip fracture is lower in men than in women, men are twice as
      likely to die after a hip fracture. Bone mineral density measurement with a T
      score of -2.5 or less indicates osteoporosis. The American College of Physicians
      recommends beginning periodic osteoporosis risk assessment in men before 65 years
      of age and performing dual-energy x-ray absorptiometry for men at increased risk
      of osteoporosis who are candidates for drug therapy. All men diagnosed with
      osteoporosis should be evaluated for secondary causes of bone loss. The decision
      regarding treatment of osteoporosis should be based on clinical evaluation,
      diagnostic workup, fracture risk assessments, and bone mineral density
      measurements. Pharmacotherapy is recommended for men with osteoporosis and for
      high-risk men with low bone mass (osteopenia) with a T-score of -1 to -2.5.
      Bisphosphonates are the first-line agents for treating osteoporosis in men.
      Teriparatide (i.e., recombinant human parathyroid hormone) is an option for men
      with severe osteoporosis. Testosterone therapy is beneficial for men with
      osteoporosis and hypogonadism. Adequate intake of calcium and vitamin D should be
      encouraged in all men to maintain bone mass. Men should be educated regarding
      lifestyle measures, which include weight-bearing exercise, limiting alcohol
      consumption, and smoking cessation. Fall prevention strategies should be
      implemented in older men at risk of falls.

PMID- 20822088
TI  - Multiple erythematous-yellow, dome-shaped papules.

PMID- 20822089
TI  - Approaching an employee about her weight.

PMID- 20822092
TI  - Proteomic identification of haptoglobin alpha2 as a glioblastoma serum biomarker:
      implications in cancer cell migration and tumor growth.
AB  - Glioblastoma (GBM; grade IV astrocytoma) is the most malignant and common primary
      brain tumor in adults. Using combination of 2-DE and MALDI-TOF MS, we analyzed 14
      GBM and 6 normal control sera and identified haptoglobin alpha2 chain as an up
      regulated serum protein in GBM patients. GBM-specific up-regulation was confirmed
      by ELISA based quantitation of haptoglobin (Hp) in the serum of 99 GBM patients
      as against lower grades (49 grade III/AA; 26 grade II/DA) and 26 normal
      individuals (p = 0.0001). Further validation using RT-qPCR on an independent set
      (n = 78) of tumor and normal brain (n = 4) samples and immunohistochemcial
      staining on a subset (n = 42) of above samples showed increasing levels of
      transcript and protein with tumor grade and were highest in GBM (p = <0.0001 and
      <0.0001, respectively). Overexpression of Hp either by stable integration of Hp
      cDNA or exogenous addition of purified Hp to immortalized astrocytes resulted in
      increased cell migration. RNAi-mediated silencing of Hp in glioma cells decreased
      cell migration. Further, we demonstrate that both human glioma and mouse melanoma
      cells overexpressing Hp showed increased tumor growth. Thus, we have identified
      haptoglobin as a GBM-specific serum marker with a role on glioma tumor growth and
      migration.

PMID- 20822093
TI  - Combined chemo-immunotherapy as a prospective strategy to combat cancer: a
      nanoparticle based approach.
AB  - The prime objective of this study was to develop a combined chemo
      immunotherapeutic formulation which could directly kill cancer cells as well as
      activate the immunosuppressed tumor microenvironment to mount a robust antitumor
      immune response. Paclitaxel (PTX) and SP-LPS (nontoxic derivative of
      lipopolysaccharide) were selected as anticancer drug and immunostimulant
      respectively. Poly(lactic-co-glycolic acid) (PLGA) based PTX and SP-LPS
      containing nanoparticles (TLNP) were prepared by the double-emulsion method
      (w/o/w) and characterized in terms of size, zeta potential and transmission
      electron microscopy (TEM). The release behavior of PTX and SP-LPS from the TLNP
      exhibited a biphasic pattern characterized by an initial burst followed by slow
      continuous release. In vitro anticancer activity of TLNP was found to be higher
      compared to PTX when studied in a tumor cell-splenocyte coculture system. TLNP
      activated murine monocytes induced the secretion of various proinflammatory
      cytokines. After iv administration of TLNP in tumor bearing C57BL/6 mice, the
      amount of PTX in the tumor mass was found to be higher in TLNP treated mice as
      compared to commercial Taxol group at all time points studied. In vitro studies
      suggest that nanoparticles containing PTX and SP-LPS have both direct
      cytotoxicity and immunostimulatory activity. Hence this might have potential as a
      chemo-immunotherapeutic formulation against cancer with advantage over present
      day chemotherapy with Taxol, in terms of tumor targeting, less toxicity and
      immunostimulation.

PMID- 20822094
TI  - Analysis of secreted proteins as an in vitro model for discovery of liver
      toxicity markers.
AB  - Despite the wealth of sequence data and new technologies that can scan large
      portions of the transcriptome or proteome in a single experiment, attempts to
      identify human biomarkers of toxicity have been met with limited success. We have
      adapted an in vitro model system to identify proteins secreted by a human
      hepatoma-derived cell line (HepG2/C3A) in response to toxicant exposure. Using
      quantitative proteomics, we can find alterations in the abundance of proteins at
      the source of damage-liver cells-that are likely to be present in blood samples
      of exposed animals. In a proof of concept experiment, conditioned medium from
      cells exposed to ethanol was subjected to quantitative mass spectral analysis
      after abundant proteins were immunodepleted. Eighty-seven proteins were
      identified with almost half changing in abundance. Some of these were only
      identified in the highest treatment condition and presumably result from the
      release of intracellular proteins into the medium when the cell membrane is
      disrupted upon cell death. However, the majority of the identified proteins
      reflect known consequences of ethanol exposure or alcoholism. The analysis of
      proteins found in conditioned medium after exposure to toxicants appears to be a
      useful system for the expedited discovery of potential human biomarkers.

PMID- 20822095
TI  - 3-deoxygalactosone, a "new" 1,2-dicarbonyl compound in milk products.
AB  - 1,2-Dicarbonyl compounds are formed in food during Maillard and caramelization
      reactions. 3-Deoxy-D-threo-hexos-2-ulose (3-deoxygalactosone, 3-DGal) and
      galactosone, two 1,2-dicarbonyl compounds originating from the degradation of
      galactose, were synthesized and converted to the respective quinoxalines, which
      were characterized by NMR spectroscopy. Analytical separation of the quinoxalines
      from the epimeric glucose-derived quinoxalines of 3-deoxyglucosone (3-DG) and
      glucosone was achieved by RP-HPLC on an RP-phenyl column. This method was used to
      study the relevance of galactose-derived 1,2-dicarbonyl compounds in a variety of
      foods. 3-DG and 3-DGal were quantified besides 3-deoxypentosone, methylglyoxal,
      and glyoxal after derivatization with o-phenylenediamine in lactose-hydrolyzed
      UHT milk, ranging from 2.5 to 18 mg/L and from 2.0 to 11 mg/L, respectively. The
      concentrations of both compounds tended to be higher in other lactose-hydrolyzed
      food items as well. During storage of lactose-hydrolyzed milk, the concentrations
      of the 3-deoxyhexosones first increased, but especially the concentration of 3
      DGal tended to decrease on prolonged storage, pointing to lower stability of the
      compound. 3-DGal was also detected in galactose-free food items such as apple
      juice and beer. The possible formation of 3-DGal from 3-DG by 3,4
      dideoxyglucosone-3-ene as an intermediate is discussed. Compared to the
      relatively high concentrations of 3-DG and 3-DGal, 3-deoxypentosone,
      methylglyoxal, and glyoxal were of only minor quantitative importance in all
      foods studied.

PMID- 20822096
TI  - Development of bimetallic titanocene-ruthenium-arene complexes as anticancer
      agents: relationships between structural and biological properties.
AB  - A series of bimetallic titanium-ruthenium complexes of general formula [(eta(5)
      C(5)H(5))(MU-eta(5):kappa(1)-C(5)H(4)(CR(2))(n)PR'R'')TiCl(2)](eta(6)-p
      cymene)RuCl(2) (n = 0, 1, 2 or 4; R = H or Me; R' = H, Ph, or Cy; R'' = Ph or Cy)
      have been synthesized, including two novel compounds as well as two cationic
      derivatives of formula [(eta(5)-C(5)H(5))(MU-eta(5):kappa(1)
      C(5)H(4)(CH(2))(n)PPh(2))TiCl(2)] [(eta(6)-p-cymene)RuCl](BF(4)) (n = 0 or 2).
      The solid state structure of two of these compounds was also established by X-ray
      crystallography. The complexes showed a cytotoxic effect on human ovarian cancer
      cells and were markedly more active than their Ti or Ru monometallic analogues
      titanocene dichloride and RAPTA-C, respectively. Studies of cathepsin B
      inhibition, an enzyme involved in cancer progression, showed that enzyme
      inhibition by the bimetallic complexes is influenced by the length of the alkyl
      chain in between the metal centers. Complementary ESI-MS studies provided
      evidence for binding of a Ru(II) fragment to proteins.

PMID- 20822097
TI  - tRNA binding properties of eukaryotic translation initiation factor 2 from
      Encephalitozoon cuniculi.
AB  - A critical consequence of the initiation of translation is the setting of the
      reading frame for mRNA decoding. In eukaryotic and archaeal cells, heterotrimeric
      initiation factor e/aIF2, in its GTP form, specifically binds Met-tRNA(i)(Met)
      throughout the translation initiation process. After start codon recognition, the
      factor, in its GDP-bound form, loses affinity for Met-tRNA(i)(Met) and eventually
      dissociates from the initiation complex. The role of each aIF2 subunit in tRNA
      binding has been extensively studied in archaeal systems. The isolated archaeal
      gamma subunit is able to bind tRNA, but the alpha subunit is required for strong
      binding. Until now, difficulties during purification have hampered the study of
      the role of each of the three subunits of eukaryotic eIF2 in specific binding of
      the initiator tRNA. Here, we have produced the three subunits of eIF2 from
      Encephalitozoon cuniculi, isolated or assembled into heterodimers or into the
      full heterotrimer. Using assays following protection of Met-tRNA(i)(Met) against
      deacylation, we show that the eukaryotic gamma subunit is able to bind by itself
      the initiator tRNA. However, the two peripheral alpha and beta subunits are
      required for strong binding and contribute equally to tRNA binding affinity. The
      core domains of alpha and beta probably act indirectly by stabilizing the tRNA
      binding site on the gamma subunit. These results, together with those previously
      obtained with archaeal aIF2 and yeast eIF2, show species-specific distributions
      of the roles of the peripheral subunits of e/aIF2 in tRNA binding.

PMID- 20822098
TI  - Reaction cycle of the dissimilatory sulfite reductase from Archaeoglobus
      fulgidus.
AB  - A vital process in the biogeochemical sulfur cycle is the dissimilatory sulfate
      reduction pathway in which sulfate (SO4-2) is converted to hydrogen sulfide
      (H2S). Dissimilatory sulfite reductase (dSir), its key enzyme, hosts a unique
      siroheme-[4Fe-4S] cofactor and catalyzes the six-electron reduction of sulfite
      (SO32-) to H2S. To explore this reaction, we determined the X-ray structures of
      dSir from the archaeon Archaeoglobus fulgidus in complex with sulfite, sulfide
      (S2-) carbon monoxide (CO), cyanide (CN-), nitrite (NO2-), nitrate (NO3-), and
      phosphate (PO43-). Activity measurements indicated that dSir of A. fulgidus
      reduces, besides sulfite and nitrite, thiosulfate (S2O32-) and trithionate (S3O62
      ) and produces the latter two compounds besides sulfide. On this basis, a three
      step mechanism was proposed, each step consisting of a two-electron transfer, a
      two-proton uptake, and a dehydration event. In comparison, the related active
      site structures of the assimilatory sulfite reductase (aSir)- and dSir-SO32
      complexes reveal different conformations of Argalpha170 and Lysalpha211 both
      interacting with the sulfite oxygens (its sulfur atom coordinates the siroheme
      iron), a sulfite rotation of ~60 degrees  relative to each other, and different
      access of solvent molecules to the sulfite oxygens from the active site cleft.
      Therefore, solely in dSir a further sulfite molecule can be placed in van der
      Waals contact with the siroheme-ligated sulfite or sulfur-oxygen intermediates
      necessary for forming thiosulfate and trithionate. Although reported for dSir
      from several sulfate-reducing bacteria, the in vivo relevance of their formation
      is questionable.

PMID- 20822099
TI  - Synthesis of 1,4-bis[2,2-bis(4-alkoxyphenyl)vinyl]benzenes and side chain
      modulation of their solid-state emission.
AB  - A series of 1,4-bis[2,2-bis(4-alkoxyphenyl)vinyl]benzene molecules with
      aggregation-induced emission (AIE) activity were synthesized. The conformations
      and packing arrangements of these molecules in the solid state can be adjusted by
      changing the side chains, which subsequently modulates their solid-state
      emission. The fluorescence quantum yield of 1e with the n-C(6)H(13) side chain in
      the solid state could reach up to 60.3% in the solid state.

PMID- 20822100
TI  - Construction of methylenecycloheptane frameworks through 7-exo-dig cyclization of
      acetylenic silyl enol ethers catalyzed by triethynylphosphine-gold complex.
AB  - A cationic gold(I) complex bearing a semihollow-shaped triethynylphosphine ligand
      efficiently catalyzed the 7-exo-dig cyclization of silyl enol ethers with an
      omega-alkynic substituent. The reaction gave various methylenecycloheptane
      derivatives with an exo- or endocyclic carbonyl group. The protocol was
      applicable not only to cyclic substrates that form bicyclic frameworks but also
      to acyclic ones with or without substituents in a carbon chain tether.

PMID- 20822101
TI  - Global concentrations of gaseous elemental mercury and reactive gaseous mercury
      in the marine boundary layer.
AB  - Gaseous elemental mercury (GEM) and reactive gaseous mercury (RGM) were measured
      during an eight month circumnavigation to obtain knowledge of their worldwide
      distributions in the marine boundary layer (MBL). Background GEM concentrations
      were found to be 1.32 +/- 0.2 ng/m(3) (summer) and 2.62 +/- 0.4 ng/m(3) (spring)
      in the northern hemisphere and 1.27 +/- 0.2 ng/m(3) (spring and summer) in the
      southern hemisphere. Radiation and relative humidity are shown to control diurnal
      cycles of RGM. During the cruise the ship passed areas of clean MBL air, air
      influenced by biomass burning (South Atlantic) and air with high concentrations
      of GEM and RGM of unknown origin (Antarctic). High GEM concentrations above the
      Atlantic indicate that emission from the ocean can be an important GEM source.
      Our data combined with data from earlier cruises provides adequate information to
      establish a seasonal cycle for the Atlantic. Results show a cycle similar to that
      found at Mace Head, Ireland but with larger amplitude. We have improved the basic
      knowledge of mean GEM and RGM concentrations in the MBL worldwide and shown how
      natural sources and reemissions can affect GEM concentrations in the MBL.

PMID- 20822102
TI  - Glycan array on aluminum oxide-coated glass slides through phosphonate chemistry.
AB  - A new type of glycan array covalently or noncovalently attached to aluminum oxide
      coated glass (ACG) slides has been developed for studies of enzymatic reactions
      and protein binding. To prepare the noncovalent array, glycans with a
      polyfluorinated hydrocarbon (-C(8)F(17)) tail are spotted robotically onto the
      ACG slide surface containing a layer of polyfluorinated hydrocarbon terminated
      with phosphonate. After incubation and washing, the noncovalent array can be
      characterized by MS-TOF via ionization/desorption at a low laser energy without
      addition of matrix. A representative cellotetraose array was developed to study
      the activity and specificity of different cellulases and to differentiate the exo
      and endoglucanase activities. To prepare the covalent array, glycans with a
      phosphonic acid tail were synthesized and spotted robotically onto the ACG slide
      surface. After incubation, the slides can be used directly for quantitative
      protein binding analysis. Compared to the preparation of glycan arrays on glass
      slides and other surfaces, this method of arraying using phosphonic acid reacting
      with ACG is more direct, convenient, and effective and represents a new platform
      for the high-throughput analysis of protein-glycan interactions.

PMID- 20822103
TI  - Transmembrane structures for Alzheimer's Abeta(1-42) oligomers.
AB  - We model oligomers of the Alzheimer's amyloid beta-peptide Abeta(1-42) in an
      implicit membrane to obtain insight into the mechanism of amyloid toxicity. It
      has been suggested that Abeta oligomers are the toxic species, causing membrane
      disruption in neuronal cells due to pore formation. We use basin-hopping global
      optimization to identify the most stable structures for the Abeta(1-42) peptide
      monomer and small oligomers up to the octamer inserted into a lipid bilayer. To
      improve the efficacy of the basin-hopping approach, we introduce a basin-hopping
      parallel tempering scheme and an oligomer generation procedure. The most stable
      membrane-spanning structure for the monomer is identified as a beta-sheet, which
      exhibits the typical strand-turn-strand motif observed in NMR experiments. We
      find ordered beta-sheets for the dimer to the hexamer, whereas for the octamer,
      we observe that the ordered structures separate into distinct tetrameric units
      that are rotated or shifted with respect to each other. This effect leads to an
      increase in favorable peptide-peptide interactions, thereby stabilizing the
      membrane-inserted octamer. On the basis of these results, we suggest that Abeta
      pores may consist of tetrameric and hexameric beta-sheet subunits. These Abeta
      pore models are consistent with the results of biophysical and biochemical
      experiments.

PMID- 20822104
TI  - Euphorbia peroxidase catalyzes thiocyanate oxidation in two different ways, the
      distal calcium ion playing an essential role.
AB  - The oxidation of the pseudohalide thiocyanate (SCN(-)) by Euphorbia peroxidase,
      in the presence or absence of added calcium, is investigated. After incubation of
      the native enzyme with hydrogen peroxide, the formation of Compound I occurs and
      serves to catalyze the thiocyanate oxidation pathways. The addition of a
      stoichiometric amount of SCN(-) to Compound I leads to the native enzyme
      spectrum; this process clearly occurs via two electron transfers from
      pseudohalide to Compound I. In the presence of 10 mM calcium ions, the addition
      of a stoichiometric amount of SCN(-) to Compound I leads to the formation of
      Compound II that returns to the native enzyme after addition of a successive
      stoichiometric amount of SCN(-), indicating that the oxidation occurs via two
      consecutive one-electron transfer steps. Moreover, different reaction products
      can be detected when the enzyme-hydrogen peroxide-thiocyanate reaction is
      performed in the absence or presence of 10 mM Ca(2+) ions. The formation of
      hypothiocyanous acid is easy demonstrated in the absence of added calcium,
      whereas in the presence of this ion, CN(-) is formed as a reaction product that
      leads to the formation of an inactive species identified as the peroxidase-CN(-)
      complex. Thus, although monomeric, Euphorbia peroxidase is an allosteric enzyme,
      finely tuned by Ca(2+) ions. These ions either can enhance the catalytic
      efficiency of the enzyme toward some substrates or can regulate the ability of
      the enzyme to exploit different metabolic pathways toward the same substrate.

PMID- 20822106
TI  - Kinetic studies of the interaction of beta-lactoglobulin with model membranes:
      stopped-flow CD and fluorescence studies.
AB  - beta-Lactoglobulin (betaLG) is a member of the lipocalin protein family and has
      been shown to undergo changes in structure upon interaction with various
      surfactants and lipid vesicles. Dynamic light scattering (DLS) and Fourier
      transform infrared (FTIR) were used to study the interaction of
      dimyristoylphosphatidylglycerol (DMPG) vesicles with betaLG and showed that the
      vesicles increase in size and become more dispersed and the transitions become
      broader but the lipid IR spectra and transition temperatures are stable.
      Fluorescence studies with vesicles with trapped calcein demonstrate betaLG
      binding induces leakage in DMPG vesicles. To study the dynamics of the
      interaction between betaLG and lipid vesicles further, we undertook kinetic
      studies using stopped-flow methods. Following previous equilibrium studies, three
      lipids, DMPG, dioleoylphosphatidylglycerol, and distearoylphosphatidylglycerol,
      all having the same negatively charged headgroup but with different acyl chain
      lengths, were used to prepare vesicles. Kinetic circular dichroism and
      fluorescence decays were measured simultaneously to monitor changes in secondary
      and tertiary structures, respectively. These were fit to either single- or double
      exponential functions, and a multistep model, with at least two intermediate
      states, has been proposed to explain the major states seen in the kinetic
      interaction of betaLG with lipid vesicles.

PMID- 20822107
TI  - Three-dimensional structures reveal multiple ADP/ATP binding modes for a
      synthetic class of artificial proteins.
AB  - The creation of synthetic enzymes with predefined functions represents a major
      challenge in future synthetic biology applications. Here, we describe six
      structures of de novo proteins that have been determined using protein
      crystallography to address how simple enzymes perform catalysis. Three structures
      are of a protein, DX, selected for its stability and ability to tightly bind ATP.
      Despite the addition of ATP to the crystallization conditions, the presence of a
      bound but distorted ATP was found only under excess ATP conditions, with ADP
      being present under equimolar conditions or when crystallized for a prolonged
      period of time. A bound ADP cofactor was evident when Asp was substituted for Val
      at residue 65, but ATP in a linear configuration is present when Phe was
      substituted for Tyr at residue 43. These new structures complement previously
      determined structures of DX and the protein with the Phe 43 to Tyr substitution
      [Simmons, C. R., et al. (2009) ACS Chem. Biol. 4, 649-658] and together
      demonstrate the multiple ADP/ATP binding modes from which a model emerges in
      which the DX protein binds ATP in a configuration that represents a transitional
      state for the catalysis of ATP to ADP through a slow, metal-free reaction capable
      of multiple turnovers. This unusual observation suggests that design-free methods
      can be used to generate novel protein scaffolds that are tailor-made for
      catalysis.

PMID- 20822105
TI  - Design, synthesis, and crystal structures of 6-alkylidene-2'-substituted
      penicillanic acid sulfones as potent inhibitors of Acinetobacter baumannii OXA-24
      carbapenemase.
AB  - Class D beta-lactamases represent a growing and diverse class of penicillin
      inactivating enzymes that are usually resistant to commercial beta-lactamase
      inhibitors. As many such enzymes are found in multi-drug resistant (MDR)
      Acinetobacter baumannii and Pseudomonas aeruginosa, novel beta-lactamase
      inhibitors are urgently needed. Five unique 6-alkylidene-2'-substituted
      penicillanic acid sulfones (1-5) were synthesized and tested against OXA-24, a
      clinically important beta-lactamase that inactivates carbapenems and is found in
      A. baumannii. Based upon the roles Tyr112 and Met223 play in the OXA-24 beta
      lactamase, we also engineered two variants (Tyr112Ala and Tyr112Ala,Met223Ala) to
      test the hypothesis that the hydrophobic tunnel formed by these residues
      influences inhibitor recognition. IC(50) values against OXA-24 and two OXA-24
      beta-lactamase variants ranged from 10 +/- 1 (4 vs WT) to 338 +/- 20 nM (5 vs
      Tyr112Ala, Met223Ala). Compound 4 possessed the lowest K(i) (500 +/- 80 nM vs
      WT), and 1 possessed the highest inactivation efficiency (k(inact)/K(i) = 0.21 +/
      0.02 MUM(-1)  s(-1)). Electrospray ionization mass spectrometry revealed a
      single covalent adduct, suggesting the formation of an acyl-enzyme intermediate.
      X-ray structures of OXA-24 complexed to four inhibitors (2.0-2.6 A) reveal the
      formation of stable bicyclic aromatic intermediates with their carbonyl oxygen in
      the oxyanion hole. These data provide the first structural evidence that 6
      alkylidene-2'-substituted penicillin sulfones are effective mechanism-based
      inactivators of class D beta-lactamases. Their unique chemistry makes them
      developmental candidates. Mechanisms for class D hydrolysis and inhibition are
      discussed, and a pathway for the evolution of the BlaR1 sensor of Staphylococcus
      aureus to the class D beta-lactamases is proposed.

PMID- 20822108
TI  - Detection of association and fusion of giant vesicles using a fluorescence
      activated cell sorter.
AB  - We have developed a method to evaluate the fusion process of giant vesicles using
      a fluorescence-activated cell sorter (FACS). Three fluorescent markers and FACS
      technology were used to evaluate the extent of association and fusion of giant
      vesicles. Two fluorescent markers encapsulated in different vesicle populations
      were used as association markers; when these vesicles associate, the two
      independent markers should be observed simultaneously in a single detection
      event. The quenched fluorescent marker and the dequencher, which were
      encapsulated in separate vesicle populations, were used as the fusion marker.
      When the internal aqueous solutions mix, the quenched marker is liberated by the
      dequencher and emits the third fluorescent signal. Although populations of pure
      POPC vesicles showed no detectable association or fusion, the same populations,
      oppositely charged by the exogenous addition of charged amphiphiles, showed up to
      50% association and 30% fusion upon population analysis of 100,000 giant
      vesicles. Although a substantial fraction of the vesicles associated in response
      to a small amount of the charged amphiphiles (5% mole fraction compared to POPC
      alone), a larger amount of the charged amphiphiles (25%) was needed to induce
      vesicle fusion. The present methodology also revealed that the association and
      fusion of giant vesicles was dependent on size, with larger giant vesicles
      associating and fusing more frequently.

PMID- 20822109
TI  - Controlled assembly of silane-based polymers: chemically robust thin-films.
AB  - We describe the controlled assembly of silane-based copolymers on various
      interfaces that have surface silanol groups. This assembly occurs as a result of
      the formation of very robust siloxane bonds (Si-O-Si) due to a condensation
      reaction between the alkoxysilane groups of the polymers and surface hydroxyl
      groups of the substrates. Deposition of these copolymers is not self-limiting;
      therefore, they could not be assembled into discrete monolayers. However, UV
      visible data collected as a function of deposition cycle reveals a linear
      relationship, confirming the deposition of a constant amount of polymer in each
      deposition cycle. A linear variation of layer thickness with deposition cycles is
      also observed. The assembled polymer layers are found to be very robust and
      resistant even when exposed to piranha solution for several hours.

PMID- 20822111
TI  - Solubility increases associated with crystalline drug nanoparticles:
      methodologies and significance.
AB  - In this manuscript, the determination of solubility of crystalline drug
      nanosuspensions by a range of methods is critically investigated. As the
      determinations of solubility were performed in the presence of the solubilizing
      nanosuspension stabilizer d-alpha-tocopherol polyethylene glycol 1000 succinate
      (TPGS), the potential effects of this excipient on the measurements were studied
      first. Solubility data of nanosuspensions of itraconazole, loviride, phenytoin
      and naproxen were generated using different methodologies. Data obtained using
      separation-based methodologies (centrifugation, filtration and
      ultracentrifugation) proved to be of limited use, due to poor nanoparticle
      separation efficiencies and/or significant adsorption of TPGS onto the
      nanoparticle surfaces. Light scattering and turbidity were found to be more
      suitable for the determination of nanosuspension solubility. The obtained data
      show that, unlike earlier reports, the solubility increases due to nanosizing are
      small, with measured increases of only 15%. These solubility increases are in
      fair agreement with what would be predicted based on the Ostwald-Freundlich
      equation.

PMID- 20822112
TI  - Plasmon-enhanced luminescence from ultrathin hybrid polymer nanoassemblies for
      microscopic oxygen sensor application.
AB  - Plasmon-enhanced luminescence was developed for luminescent oxygen sensor
      application. Luminescent polymer Langmuir-Blodgett films containing platinum
      porphyrin were assembled plane-to-plane with a silver nanoparticle array. The
      hybrid polymer nanoassemblies allow more than 10-fold luminescence enhancement in
      air. The luminescence intensity and lifetime measurements as functions of the
      number of layers revealed that some platinum-porphyrin, which is close to silver
      nanoparticles, is effectively enhanced. The enhancement enables us to monitor 2D
      oxygen distribution mapping on the micrometer scale.

PMID- 20822110
TI  - Internalization of p53(14-29) peptide amphiphiles and subsequent endosomal
      disruption results in SJSA-1 cell death.
AB  - In vivo peptide inhibition of tumor suppressor p53 binding to the protein MDM2 is
      hampered by inefficient delivery of the peptide. Our approach to couple a
      hydrophobic lipid-like tail on the inhibitory peptide p53(14-29) allowed its
      intracellular delivery in vitro, in a panel of different cell lines. The
      constructed chimeric molecules, termed peptide amphiphiles, further self
      assembled into supramolecular structures, identified as elongated wormlike
      micelles. Internalization of peptides occurred following micelle disassembly,
      partly via clathrin-mediated endocytosis of monomers. Incubation of SJSA-1 cells
      in hypertonic culture media, aimed to disrupt endocytic vesicles, resulted in
      peptide amphiphile-mediated cell death. Our results provide the basis for the
      construction of novel therapeutic supramolecular nanoparticles and suggest
      hydrophobic modification of peptides as a promising strategy for enhancing
      delivery of impermeable peptides.

PMID- 20822113
TI  - Archaeal RibL: a new FAD synthetase that is air sensitive.
AB  - FAD synthetases catalyze the transfer of the AMP portion of ATP to FMN to produce
      FAD and pyrophosphate (PP(i)). Monofunctional FAD synthetases exist in
      eukaryotes, while bacteria have bifunctional enzymes that catalyze both the
      phosphorylation of riboflavin and adenylation of FMN to produce FAD. Analyses of
      archaeal genomes did not reveal the presence of genes encoding either group, yet
      the archaea contain FAD. Our recent identification of a CTP-dependent archaeal
      riboflavin kinase strongly indicated the presence of a monofunctional FAD
      synthetase. Here we report the identification and characterization of an archaeal
      FAD synthetase. Methanocaldococcus jannaschii gene MJ1179 encodes a protein that
      is classified in the nucleotidyl transferase protein family and was previously
      annotated as glycerol-3-phosphate cytidylyltransferase (GCT). The MJ1179 gene was
      cloned and its protein product heterologously expressed in Escherichia coli. The
      resulting enzyme catalyzes the adenylation of FMN with ATP to produce FAD and
      PP(i). The MJ1179-derived protein has been designated RibL to indicate that it
      follows the riboflavin kinase (RibK) step in the archaeal FAD biosynthetic
      pathway. Aerobically isolated RibL is active only under reducing conditions. RibL
      was found to require divalent metals for activity, the best activity being
      observed with Co(2+), where the activity was 4 times greater than that with
      Mg(2+). Alkylation of the two conserved cysteines in the C-terminus of the
      protein resulted in complete inactivation. RibL was also found to catalyze
      cytidylation of FMN with CTP, making the modified FAD, flavin cytidine
      dinucleotide (FCD). Unlike other FAD synthetases, RibL does not catalyze the
      reverse reaction to produce FMN and ATP from FAD and PP(i). Also in contrast to
      other FAD synthetases, PP(i) inhibits the activity of RibL.

PMID- 20822114
TI  - Patterning of functional compounds by multicomponent Langmuir-Blodgett transfer
      and subsequent chemical modification.
AB  - The multicomponent transfer of functional molecules by Langmuir-Blodgett (LB)
      technique onto solid substrates offers an interesting route for generation of
      functionalized patterns by self-assembly over large surface areas. In the present
      paper, we discuss LB transfer of mixed LB films containing different functional
      amphiphiles (an azide, an estrone derivate, a lithocholic acid derivative, or an
      alkoxyamine) in combination with dipalmitoylphosphatidyl choline (DPPC). The
      effect of the mixing ratio on pattern formation is discussed, and we provide some
      general design rules for the synthesis of functional molecules to be applicable
      for the multicomponent LB transfer process. We show that these functional
      compounds can be successfully transferred to oxidized Si wafers in stripe
      pattern. Covalent attachment of the functional entities is easily achieved, and
      the patterned surfaces are then ready for further chemical manipulation. This is
      demonstrated by site-specifically covalent attaching dye molecules applying the
      copper(l)-catalyzed alkyne azide click reaction (CuAAC), the thiol-ene reaction,
      and a surface-initiated radical polymerization.

PMID- 20822115
TI  - Reverse vesicles from a salt-free catanionic surfactant system: a confocal
      fluorescence microscopy study.
AB  - We give a detailed confocal fluorescence microscopy study on reverse vesicles
      from a salt-free catanionic surfactant system. When tetradecyltrimethylammonium
      laurate (TTAL) and lauric acid (LA) are mixed in cyclohexane at the presence of a
      small amount of water, stable reverse vesicular phases form spontaneously. The
      reverse vesicular phases can be easily labeled with dyes of varying molecular
      size and hydrophobicity while the dyes are nearly insoluble in cyclohexane
      without reverse vesicles. This indicates the reverse vesicular phases can be good
      candidates to host guest molecules. With the help of a fluorescence microscope
      combined a confocal method, the features of these interesting reverse
      supramolecular self-assemblies were revealed for the first time. Because of the
      absence of electrostatic repulsions and hydration forces between adjacent
      vesicles, the reverse vesicles have a strong propensity to aggregate with each
      other and form three-dimensional clusters. The size distributions of both
      individual reverse vesicles and clusters are polydisperse. Huge multilamellar
      reverse vesicles with closely stacked thick walls (giant reverse onions) were
      observed. Besides the spherical reverse vesicles and onions, other supramolecular
      structures such as tubes have also been detected and structural evolutions
      between different structures were noticed. These interesting supramolecular self
      assemblies form in a nonpolar organic solvent may serve as ideal micro- or
      nanoreaction centers for biological reactions and synthesis of inorganic
      nanomaterials.

PMID- 20822116
TI  - Synthesis of dibenzazepinones by palladium-catalyzed intramolecular arylation of
      o-(2'-bromophenyl)anilide enolates.
AB  - A new approach for the convenient synthesis of dibenzazepinones is reported. The
      key step is the formation of the seven-membered ring through palladium-catalyzed
      intramolecular arylation of an anilide enolate. The reactions were completed in
      10 min at 100  degrees C with moderate to excellent yields. Aminodibenzazepinone
      1, the core structure in the gamma-secretase inhibitor LY411575, can be prepared
      in five steps from 2-bromophenylboronic acid and 2-iodoaniline in 60% overall
      yield. The synthesis reported here compares favorably with presently available
      approaches to this interesting ring system.

PMID- 20822117
TI  - Dynamic perspective on the function of thermoresponsive nanopores from in situ
      AFM and ATR-IR investigations.
AB  - This article describes the morphological and chemical characterization of stimuli
      responsive functionalized silicon surfaces provided in parallel by atomic force
      spectroscopy (AFM) and Fourier transform infrared spectroscopy (FT-IR) enhanced
      by the single-beam sample reference attenuated total reflection method (SBSR
      ATR). The stimuli-responsive behavior of the surfaces was obtained by grafting-to
      in melt carboxyl-terminated poly-N-isopropylacryl amides (PNIPAAM) with different
      degree of polymerization (DP) on epoxide-functionalized silicon substrates. The
      unprecedented real time and in situ physicochemical insight into the temperature
      triggered response of the densely packed superficial brushes allowed for the
      selection of a PNIPAAM with a specific DP as a suitable polymer for the
      fabrication of silicon membranes exhibiting switchable nanopores. The fabrication
      process combines the manufacture of nanoporous silicon surfaces and their
      subsequent chemical functionalization by the grafting-to in melt of the selected
      polymer. Then, relevant information was obtained in what concerns the chemical
      modifications behind the topographical changes that drive the functioning of
      PNIPAAM-based hybrid nanovalves as well as the timescale on which the opening and
      closing of the nanopores occur.

PMID- 20822118
TI  - Frequency-induced stratification in viscoelastic microfluidics.
AB  - We present a mechanism in the field of microfluidics by which the stratification
      of a viscoelastic fluid can be induced in a channel on the microscale by applying
      a dynamic pressure gradient at frequencies within the range of sound.
      Stratification is obtained with identical layers, parallel to the channel walls,
      whose number can be tailored. These layers are separated by 2D zero-velocity
      planes. This would allow different tracer particles with small diffusion
      coefficients to be confined in different fluid layers within the same
      microchannel. We obtain analytical results that allow us to make theoretical
      predictions regarding the possible experimental realization of stratification in
      a microchannel using a biofluid. We find a relation among the diffusion
      coefficient, fluid properties, and microchannel thickness that establishes a
      condition for the confinement of tracer particles to a layer. This mechanism has
      potential use in micrototal analysis systems and MEMS-containing viscoelastic
      fluids.

PMID- 20822119
TI  - Copper-catalyzed thiolation of the di- or trimethoxybenzene arene C-H bond with
      disulfides.
AB  - A CuI-catalyzed direct access to sulfides from disulfides via C-H bond cleavage
      of di- or trimethoxybenzene is described. The procedure utilizes O(2) as a clean
      and cheap oxidant. Direct selenation of the C-H bond also took place under this
      procedure. Furthermore, the system enables the use of two RS in (RS)(2). Thus, it
      represents an atom-economical procedure for the synthesis of sulfides and
      selenides.

PMID- 20822120
TI  - A versatile and practical solvating agent for enantioselective recognition and
      NMR analysis of protected amines.
AB  - The 3,5-dinitrobenzoyl-derived 1-naphthylethyl amide 3 is an attractive CSA for
      NMR analysis of protected amines. It is readily prepared in a single step and
      combines practical resolution of diastereomeric complexes due to signal sharpness
      and effective signal separation. Crystallographic analysis shows that 3 forms a
      chiral cleft that can selectively bind one enantiomer of a substrate through
      hydrogen bonding, pi-pi stacking, and CH/pi interactions. The enantioselective
      complex formation causes strong upfield shifts in the (1)H NMR spectrum even in
      the presence of only 5 mol % of 3.

PMID- 20822121
TI  - Modular approach to triazole-linked 1,6-alpha-D-oligomannosides to the discovery
      of inhibitors of Mycobacterium tuberculosis cell wall synthetase.
AB  - Aiming at developing inhibitors of mannosyltransferases, the enzymes that
      participate in the biosynthesis of the cell envelope of Mycobacterium
      tuberculosis, the synthesis of a range of designed triazole-linked 1,6
      oligomannosides up to a hexadecamer has been accomplished by a modular approach
      centered on the Cu(I)-catalyzed azide-alkyne cycloaddition as key process. The
      efficiency and fidelity of the cycloaddition are substantiated by high yields (76
      96%) and exclusive formation of the expected 1,4-disubstituted triazole ring in
      all oligomer assembling reactions. Key features of oligomers thus prepared are
      the anomeric carbon-carbon bond of all mannoside residues and the 6
      deoxymannoside capping residue. Suitable bioassays with dimer, tetramer, hexamer,
      octamer, decamer, and hexadecamer showed variable inhibitor activity against
      mycobacterial alpha-(1,6)-mannosyltransferases, the highest activity (IC(50) =
      0.14-0.22 mM) being registered with the hexamannoside and octamannoside.

PMID- 20822122
TI  - Electrostatic stabilization of charged colloidal particles with adsorbed
      polyelectrolytes of opposite charge.
AB  - Repulsive electrostatic double-layer forces are responsible for the stabilization
      of charged colloidal particles in the presence of adsorbed polyelectrolytes of
      opposite and high line charge densities. This mechanism is revealed by studies of
      electrophoretic mobility and colloidal stability performed with dynamic light
      scattering as a function of the polyelectrolyte dose and the ionic strength for
      two different types of latex particles and four different types of
      polyelectrolytes. The dependence of these quantities is very similar for bare
      charged latex particles and the same particles in the presence of the different
      oppositely charged polyelectrolytes. Positively charged particles in the presence
      of anionic polyelectrolytes behave analogously to negatively charged particles in
      the presence of cationic polyelectrolytes.

PMID- 20822123
TI  - Experimental study of methane replacement in gas hydrate by carbon dioxide.
AB  - The process of replacement of methane molecules in clathrate hydrate by carbon
      dioxide is studied experimentally. The dependence of the replacement extent on
      the concentration of the gas mixture coexisting with the hydrate is determined.
      The kinetics of the replacement is governed by two relaxation modes with a
      characteristic time ratio of about 10.

PMID- 20822124
TI  - Influence of hydrostatic pressure on dynamics and spatial distribution of protein
      partial molar volume: time-resolved surficial Kirkwood-Buff approach.
AB  - The influence of hydrostatic pressure on the partial molar volume (PMV) of the
      protein apomyoglobin (AMb) was investigated by all-atom molecular dynamics (MD)
      simulations. Using the time-resolved Kirkwood-Buff (KB) approach, the dynamic
      behavior of the PMV was identified. The simulated time average value of the PMV
      and its reduction by 3000 bar pressurization correlated with experimental data.
      In addition, with the aid of the surficial KB integral method, we obtained the
      spatial distributions of the components of PMV to elucidate the detailed
      mechanism of the PMV reduction. New R-dependent PMV profiles identified the
      regions that increase or decrease the PMV under the high pressure condition. The
      results indicate that besides the hydration in the vicinity of the protein
      surface, the outer space of the first hydration layer also significantly
      influences the total PMV change. These results provide a direct and detailed
      picture of pressure induced PMV reduction.

PMID- 20822125
TI  - Reduction rate constants for nitroaromatic compounds estimated from adiabatic
      electron affinities.
AB  - Nitroaromatic compounds (NACs) are ubiquitous environmental contaminants and
      predicting their environmental fate is important. Linear free energy
      relationships (LFERs) have been reported relating one-electron reduction
      potentials (E(o)(H)) of NACs in water to their reduction rate constants (k)
      measured under various conditions. In a recent effort to calculate E(o)(H), we
      found that E(o)(H) values of NACs are also linearly correlated with their
      adiabatic electron affinities (EA). This suggests that the reactivity of NACs-
      and hence their half-lives--can be predicted based on their EA values. We report
      here a new set of LFERs relating EA and k for NACs. Reduction of substituted
      nitrobenzenes mediated by quinones, natural organic matter, Fe(II) complexes, and
      the (CH(3))(2)COH radical was examined using EA values calculated from quantum
      mechanics. For monosubstituted nitrobenzenes without ortho substituents, strong
      linear correlations were found between EA and log k, leading to accurate
      estimates of k. Deviations between measured and estimated k values for most ortho
      substituted and/or polysubstituted compounds were somewhat higher, but were
      accurate to within approximately an order of magnitude using the same LFER for
      all compounds. We report estimates of 169 reduction rate constants for 23
      compounds in nine reducing systems for which no measured values are available.

PMID- 20822126
TI  - Simple coupling chemistry linking carboxyl-containing organic molecules to
      silicon oxide surfaces under acidic conditions.
AB  - The coupling chemistry of carboxymethylated amylose with organo-silanized silicon
      oxide surfaces at pH 7.4 and 2.0 was investigated using atomic force microscopy
      (AFM) based single-molecule force spectroscopy. At close to neutral pH,
      carbodiimide activation of a carboxylic acid affords formation of an amide bond
      with an amino surface linker. At pH 2.0, no activation with carbodiimide was
      required to anchor carboxymethylated amylose between an AFM tip and a glass
      substrate. At the same time, the mean bond rupture force f(r) dropped from 1.65
      +/- 0.37 nN at pH 7.4 to 1.39 +/- 0.30 nN at pH 2.0 without carbodiimide,
      indicating that a different link to the surface can be formed at low pH. The
      coupling mechanism at pH 2.0 was elucidated by a series of experiments, in which
      the surface was functionalized with four different organosilanes, each containing
      characteristic functional groups. The results are rationalized with an acid
      catalyzed ester condensation between a carboxyl group and a free, unreacted
      silanol group in the surface anchor or on the surface.

PMID- 20822128
TI  - Assessment of sewer source contamination of drinking water wells using tracers
      and human enteric viruses.
AB  - This study investigated the source, transport, and occurrence of human enteric
      viruses in municipal well water, focusing on sanitary sewer sources. A total of
      33 wells from 14 communities were sampled once for wastewater tracers and
      viruses. Wastewater tracers were detected in four of these wells, and five wells
      were virus- positive by qRT-PCR. These results, along with exclusion of wells
      with surface water sources, were used to select three wells for additional
      investigation. Viruses and wastewater tracers were found in the groundwater at
      all sites. Some wastewater tracers, such as ionic detergents, flame retardants,
      and cholesterol, were considered unambiguous evidence of wastewater. Sampling at
      any given time may not show concurrent virus and tracer presence; however, given
      sufficient sampling over time, a relation between wastewater tracers and virus
      occurrence was identified. Presence of infectious viruses at the wellhead
      demonstrates that high-capacity pumping induced sufficiently short travel times
      for the transport of infectious viruses. Therefore, drinking-water wells are
      vulnerable to contaminants that travel along fast groundwater flowpaths even if
      they contribute a small amount of virus-laden water to the well. These results
      suggest that vulnerability assessments require characterization of "low yield
      fast transport" in addition to traditional "high yield-slow transport", pathways.

PMID- 20822127
TI  - Determination of cross sections by overtone mobility spectrometry: evidence for
      loss of unstable structures at higher overtones.
AB  - Overtone mobility spectrometry (OMS) is examined as a means of determining the
      collision cross sections for multiply charged ubiquitin and substance P ions, as
      well as for singly charged rafinose and melezitose ions. Overall, values of
      collision cross section measured by OMS for stable ion conformations are found to
      be in agreement with values determined by conventional ion mobility spectrometry
      (IMS) measurements to within ~1% relative uncertainty. The OMS spectra for
      ubiquitin ions appear to favor different conformations at higher overtones. We
      propose that the changes in the distributions as a function of the overtone
      region in which they are measured arise from the elimination of ions that undergo
      structural transitions in the drift regions. Kinetics simulations suggest that
      structural transitions occurring on the order of a few ms and resulting in an ~4%
      change in ion collision cross sections are detected by OMS measurements. The
      unique method of distinguishing ion mobilities with OMS reveals these structural
      transitions which are not readily apparent from traditional IMS measurements.

PMID- 20822129
TI  - Physiological and transcriptional studies of Cr(VI) reduction under aerobic and
      denitrifying conditions by an aquifer-derived pseudomonad.
AB  - Cr(VI) is a widespread groundwater contaminant that is a potent toxin, mutagen,
      and carcinogen. In situ reductive immobilization is a favored approach for Cr(VI)
      bioremediation, and Cr(VI) reduction has been reported in a variety of aerobic,
      facultative, and anaerobic bacteria, including a number of pseudomonads. However,
      studies comparing Cr(VI) reduction under aerobic and denitrifying conditions in
      the same organism are not available. We have conducted studies with strain RCH2,
      a bacterium similar to Pseudomonas stutzeri that we isolated from a Cr
      contaminated aquifer. Cell suspension studies with lactate demonstrated that
      Cr(VI) reduction could occur under either denitrifying or aerobic conditions (at
      comparable specific rates) and that reduction was at least 20-fold more rapid
      when the terminal electron acceptor (i.e., nitrate or O(2)) was present. Our
      results suggest that Cr(VI) reduction by strain RCH2 under either aerobic or
      denitrifying conditions is primarily cometabolic in the sense that the
      physiological electron acceptor (oxygen or nitrate) appears to be required. Under
      both aerobic and denitrifying conditions, the gene(s) associated with chromate
      reduction are not inducible by Cr. Continuous culture (chemostat) studies showed
      strong correlations (r(2) values >0.93) between nitrate reduction rate and the
      transcript copy number of either nirS (cytochrome cd(1) nitrite reductase) or
      narG (nitrate reductase alpha subunit). As our studies indicate that anaerobic
      Cr(VI) reduction by this pseudomonad requires active denitrification and that
      denitrification and chromate reduction rates are highly correlated (r(2) > 0.99),
      monitoring expression of such denitrification genes in biostimulated aquifers
      could provide valuable proxy information for in situ chromate reduction by
      similar bacteria even if the specific genes involved in chromate reduction have
      not been identified. We also report incomplete removal of reduced Cr from
      solution and on artifacts in the widely used diphenylcarbazide assay for Cr(VI),
      most notably, its complete inactivation in the presence of millimolar nitrite.

PMID- 20822130
TI  - Concomitant microbial generation of palladium nanoparticles and hydrogen to
      immobilize chromate.
AB  - The catalytic properties of various metal nanoparticles have led to their use in
      environmental remediation. Our aim is to develop and apply an efficient
      bioremediation method based on in situ biosynthesis of bio-Pd nanoparticles and
      hydrogen. C. pasteurianum BC1 was used to reduce Pd(II) ions to form Pd
      nanoparticles (bio-Pd) that primarily precipitated on the cell wall and in the
      cytoplasm. C. pasteurianum BC1 cells, loaded with bio-Pd nanoparticle in the
      presence of glucose, were subsequently used to fermentatively produce hydrogen
      and to effectively catalyze the removal of soluble Cr(VI) via reductive
      transformation to insoluble Cr(III) species. Batch and aquifer microcosm
      experiments using C. pasteurianum BC1 cells loaded with bio-Pd showed efficient
      reductive Cr(VI) removal, while in control experiments with killed or viable but
      Pd-free bacterial cultures no reductive Cr(VI) removal was observed. Our results
      suggest a novel process where the in situ microbial production of hydrogen is
      directly coupled to the catalytic bio-Pd mediated reduction of chromate. This
      process offers significant advantages over the current groundwater treatment
      technologies that rely on introducing preformed catalytic nanoparticles into
      groundwater treatment zones and the costly addition of molecular hydrogen to
      above ground pump and treat systems.

PMID- 20822131
TI  - Modeling phototransformation reactions in surface water bodies: 2,4-dichloro-6
      nitrophenol as a case study.
AB  - The anionic form of 2,4-dichloro-6-nitrophenol (DCNP), which prevails in surface
      waters over the undissociated one, has a direct photolysis quantum yield of (4.53
      +/- 0.78) * 10(-6) under UVA irradiation and second-order reaction rate constants
      of (2.8 +/- 0.3) * 10(9) M(-1) s(-1) with *OH, (3.7 +/- 1.4) * 10(9) M(-1) s(-1)
      with (1)O(2), and (1.36 +/- 0.09) * 10(8) M(-1) s(-1) with the excited triplet
      state of anthraquinone-2-sulfonate, adopted as a proxy for the photoactive
      dissolved organic compounds in surface waters. DCNP also shows negligible
      reactivity with the carbonate radical. Insertion of the data into a model of
      surface water photochemistry indicates that the direct photolysis and the
      reactions with *OH and (1)O(2) would be the main phototransformation processes of
      DCNP, with *OH prevailing in organic-poor and (1)O(2) in organic-rich waters. The
      model results compare well with the field data of DCNP in the Rhone river delta
      (Southern France), where (1)O(2) would be the main reactive species for the
      phototransformation of the substrate.

PMID- 20822132
TI  - Interplay of phenol and isopropyl isomerism in propofol from broadband chirped
      pulse microwave spectroscopy.
AB  - The conformational equilibrium of the general anesthetic propofol (2,6
      diisopropylphenol) has been studied in a supersonic expansion using broadband
      chirped-pulse microwave spectroscopy. Three conformers originated by the combined
      internal rotation of the hydroxyl and the two isopropyl groups have been detected
      in the jet-cooled rotational spectrum. The most stable conformer exhibits
      tunneling splittings associated with the internal rotation of the hydroxyl group,
      from which we determined the torsional potential and barrier heights (905-940 cm(
      1)). The carbon backbone structure was derived from the spectral assignments of
      all 12 (13)C monosubtituted isotopologues in natural abundance and confirmed a
      plane-symmetric gauche orientation of the two isopropyl groups (Gg) for this
      conformer. In the other two detected conformers (EG and GE) one of the isopropyl
      groups is eclipsed with respect to the ring plane while the other is gauche,
      differing in a ~180 degrees  rotation of the hydroxyl group. Supporting ab initio
      calculations provided information on the potential energy surface and molecular
      properties of the title compound.

PMID- 20822133
TI  - Design of new N,O hybrid pyrazole derived ligands and their use as stabilizers
      for the synthesis of Pd nanoparticles.
AB  - We describe the stabilization studies of new palladium nanoparticles (Pd NPs)
      with a family of hybrid ligands. For this purpose, two new N,O-hybrid pyrazole
      derived ligands, as well as other previously reported, have been used as NP
      stabilizing agents following an organometallic approach. A comparison with
      corresponding palladium complexes has been carried out. We have also studied the
      superstructures formed by the agglomeration of NPs. To evaluate the scope of the
      system, different parameters have been studied such as the structure of the
      ligand, the ligand/metal ratio, the nature of the solvent, the concentration and
      the reaction time. The colloidal materials resulting from the different syntheses
      were all characterized by IR, transmission electron microscopy techniques at low
      or high resolution (TEM and HR-TEM), and scanning electron microscopy (SEM-FEG).
      All these observations have allowed us to better understand the coordination
      modes of the different ligands onto the surface of the NPs.

PMID- 20822134
TI  - Copper-catalyzed regio- and enantioselective synthesis of chiral enol acetates
      and beta-substituted aldehydes.
AB  - The in situ transformation of alpha,beta-unsaturated aldehydes into alpha
      chloroallylic acetates and subsequent copper-catalyzed regio- and
      enantioselective (up to 94% ee) allylic alkylation with Grignard reagents
      provides chiral enol acetates and chiral beta-substituted aldehydes in a one-pot
      protocol.

PMID- 20822135
TI  - (110)-exposed gold nanocoral electrode as low onset potential selective glucose
      sensor.
AB  - A straightforward electrochemical deposition process was developed to grow gold
      nanostructures, including nanocoral, nanothorn, branched belt, and nanoparticle,
      on carbon electrodes by reducing HAuCl4 under constant potentials in mixtures
      containing CTAC and/or NaNO3. Among the nanostructures, the quasi-one-dimensional
      nanocoral electrode showed the highest surface area. Because of this, it provided
      excellent electrochemical performances in cyclic voltammetric (CV) studies for
      kinetic-controlled enzyme-free glucose oxidation reactions. In amperometric
      studies carried out at 0.200 V in PBS (pH 7.40, 0.100 M), the nanocoral electrode
      showed the highest anodic current response. It also offered the greatest
      sensitivity, 22.6 MUAmM(-1)cm(-2), an extended linear range, 5.00*10(-2) mM to
      3.00*10(1) mM, and a low detection limit, 1.00*10(1) MUm among the electrodes
      investigated in this study. In addition, the glucose oxidation by the nanocoral
      electrode started at -0.280 V, more negative than the one of using a commercial
      Au electrode as the working electrode. This is attributed to the presence of
      exposed Au (110) surfaces on the electrode. The feature was applied to oxidize
      glucose selectively in the presence of ascorbic acid (AA) and uric acid (UA),
      common interferences found in physiological analytes. With an applied voltage at 
      0.100 V, the AA oxidation (started at -0.080 V) can be avoided while the glucose
      oxidation still provides a significant response.

PMID- 20822136
TI  - Functionalization of metallabenzenes through nucleophilic aromatic substitution
      of hydrogen.
AB  - The cationic metallabenzenes [Ir(C(5)H(4){SMe-1})(kappa(2)
      S(2)CNEt(2))(PPh(3))(2)]PF(6) (1) and [Os(C(5)H(4){SMe
      1})(CO)(2)(PPh(3))(2)][CF(3)SO(3)] (2) undergo regioselective nucleophilic
      aromatic substitution of hydrogen at the metallabenzene ring position gamma to
      the metal in a two-step process that first involves treatment with appropriate
      nucleophiles and then oxidation. Thus, reaction between compound 1 and NaBH(4),
      MeLi, or NaOEt gives the corresponding neutral iridacyclohexa-1,4-diene complexes
      Ir(C(5)H(3){SMe-1}{H-3}{Nu-3})(kappa(2)-S(2)CNEt(2))(PPh(3))(2) (Nu = H (3), Me
      (4), OEt (5)). Similarly, reaction between 2 and NaBH(4) or MeLi gives the
      corresponding osmacyclohexa-1,4-diene complexes Os(C(5)H(3){SMe-1}{H-3}{Nu
      3})(CO)(2)(PPh(3))(2) (Nu = H (8), Me (9)). The metallacyclohexa-1,4-diene rings
      in all these compounds are rearomatized on treatment with the oxidizing agent
      O(2), CuCl(2), or 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Accordingly,
      the cationic metallabenzene 1 or 2 is returned after reaction between 3 and
      DDQ/NEt(4)PF(6) or between 8 and DDQ/NaO(3)SCF(3), respectively. The substituted
      cationic iridabenzene [Ir(C(5)H(3){SMe-1}{Me-3})(kappa(2)
      S(2)CNEt(2))(PPh(3))(2)]PF(6) (6) or [Ir(C(5)H(4){SMe-1}{OEt-3})(kappa(2)
      S(2)CNEt(2))(PPh(3))(2)]PF(6) (7) is produced in a similar manner through
      reaction between 4 or 5, respectively, and DDQ/NEt(4)PF(6), and the substituted
      cationic osmabenzene [Os(C(5)H(3){SMe-1}{Me-3})(CO)(2)(PPh(3))(2)]Cl (10) is
      formed in good yield on treatment of 9 with CuCl(2). The starting cationic
      iridabenzene 1 is conveniently prepared by treatment of the neutral iridabenzene
      Ir(C(5)H(4){SMe-1})Cl(2)(PPh(3))(2) with NaS(2)CNEt(2) and NEt(4)PF(6), and the
      related starting cationic osmabenzene 2 is obtained by treatment of Os(C(5)H(4){S
      1})(CO)(PPh(3))(2) with CF(3)SO(3)CH(3) and CO. The stepwise transformations of 1
      into 6 or 7 as well as 2 into 10 provide the first examples in metallabenzene
      chemistry of regioselective nucleophilic aromatic substitutions of hydrogen by
      external nucleophiles. DFT calculations have been used to rationalize the
      preferred sites for nucleophilic attack at the metallabenzene rings of 1 and 2.
      The crystal structures of 1, 3, 6, and 7 have been obtained.

PMID- 20822138
TI  - Folding catalysis by transient coordination of Zn2+ to the Cu ligands of the ALS
      associated enzyme Cu/Zn superoxide dismutase 1.
AB  - How coordination of metal ions modulates protein structures is not only important
      for elucidating biological function but has also emerged as a key determinant in
      protein turnover and protein-misfolding diseases. In this study, we show that the
      coordination of Zn(2+) to the ALS-associated enzyme Cu/Zn superoxide dismutase
      (SOD1) is directly controlled by the protein's folding pathway. Zn(2+) first
      catalyzes the folding reaction by coordinating transiently to the Cu ligands of
      SOD1, which are all contained within the folding nucleus. Then, after the global
      folding transition has commenced, the Zn(2+) ion transfers to the higher affinity
      Zn site, which structures only very late in the folding process. Here it remains
      dynamically coordinated with an off rate of ~10(-5) s(-1). This relatively rapid
      equilibration of metals in and out of the SOD1 structure provides a simple
      explanation for how the exceptionally long lifetime, >100 years, of holoSOD1 is
      still compatible with cellular turnover: if a dissociated Zn(2+) ion is prevented
      from rebinding to the SOD1 structure then the lifetime of the protein is reduced
      to a just a few hours.

PMID- 20822139
TI  - Top-down fabrication of alpha-Fe2O3 single-crystal nanodiscs and microparticles
      with tunable porosity for largely improved lithium storage properties.
AB  - In this work, we report a facile top-down approach to fabricate uniform single
      crystal alpha-Fe(2)O(3) nanodiscs via selective oxalic acid etching. Phosphate
      ions are employed as a capping agent to control the etching to along the [001]
      direction. We also show that alpha-Fe(2)O(3) melon-like microparticles with
      contrasting textural properties can be generated using the same approach. The
      etched particles exhibit a much larger total pore volume and average pore size
      compared to the pristine ones, thus serving as the possible origin for their
      greatly enhanced capacity retention when tested as potential anode materials for
      lithium-ion batteries.

PMID- 20822140
TI  - Glutathione-stabilized magic-number silver cluster compounds.
AB  - Magic-number theories, developed to explain the anomalous stability of clusters
      in the gas phase, are being successfully applied to explain the stability of
      families of condensed phase Au clusters. To test the generalizability of these
      theories, we have synthesized a family of magic-numbered Ag clusters. Silver
      clusters ligated with glutathione (GSH) were synthesized by reduction of silver
      glutathiolate in water and then separated by polyacrylamide gel electrophoresis
      (PAGE). The raw synthetic product consisted of a family of discrete Ag:SG
      clusters, each forming a band in the PAGE gel. Varying reaction conditions
      changed the relative abundance of the family members but not their positions and
      colors within the gel, indicating the molecular precision of magic-number
      clusters. Absorption onsets for the most abundant clusters monotonically
      decreased with increasing cluster size, and spectra contained a small number of
      peaks that corresponded to single electron transitions. Although these Ag:SG
      clusters are related to Au:SG clusters, the distribution of cluster sizes and the
      optical absorption spectra were markedly different for the two families. This
      suggests that the Ag:SG clusters are not a simple extension of the Au:SG system,
      possibly due to differences in Au and Ag chemistry. Alternatively, condensed
      phase magic-number cluster theories may need to be more complex than currently
      believed.

PMID- 20822142
TI  - Charge localization in isolated mixed-valence complexes: an STM and theoretical
      study.
AB  - {Cp*(dppe)Fe(C=C-)}(2)(1,3-C(6)H(4)) is studied both as a neutral molecule,
      Fe(II)-Fe(II), and as a mixed-valence complex, Fe(II)-Fe(III). Scanning tunneling
      microscopy (STM) is used to image these species at 77 K under ultrahigh-vacuum
      conditions. The neutral molecule Fe(II)-Fe(II) has a symmetric, "dumbbell"
      appearance in STM images, while the mixed-valence complex Fe(II)-Fe(III)
      demonstrates an asymmetric, bright-dim double-dot structure. This asymmetry
      results from localization of the electron to one of the iron-ligand centers, a
      result which is confirmed through comparison to theoretical STM images calculated
      using constrained density-functional theory (CDFT). The observation of charge
      localization in mixed-valence complexes outside of the solution environment opens
      up new avenues for the control and patterning of charge on surfaces, with
      potential applications in smart materials and molecular electronic devices.

PMID- 20822141
TI  - Rescue of K12G triosephosphate isomerase by ammonium cations: the reaction of an
      enzyme in pieces.
AB  - The K12G mutation at yeast triosephosphate isomerase (TIM) results in a 5.5 *
      10(5)-fold decrease in k(cat)/K(m) for isomerization of glyceraldehyde 3
      phosphate, and the activity of this mutant can be successfully "rescued" by
      NH(4)(+) and primary alkylammonium cations. The transition state for the K12G
      mutant TIM-catalyzed reaction is stabilized by 1.5 kcal/mol by interaction with
      NH(4)(+). The larger 3.9 kcal/mol stabilization by CH(3)CH(2)CH(2)CH(2)NH(3)(+)
      is due to hydrophobic interactions between the mutant enzyme and the butyl side
      chain of the cation activator. There is no significant transfer of a proton from
      alkylammonium cations to GAP at the transition state for the K12G mutant TIM
      catalyzed reaction, because activation by a series of RNH(3)(+) shows little or
      no dependence on the pK(a) of RNH(3)(+). A comparison of k(cat)/K(m) = 6.6 *
      10(6) M(-1) s(-1) for the wildtype TIM-catalyzed isomerization of GAP and the
      third-order rate constant of 150 M(-2) s(-1) for activation by NH(4)(+) of the
      K12G mutant TIM-catalyzed isomerization shows that stabilization of the bound
      transition state by the effectively intramolecular interaction of the cationic
      side chain of Lys-12 at wildtype TIM is 6.3 kcal/mol greater than that for the
      corresponding intermolecular interaction of NH(4)(+) at K12G mutant TIM.

PMID- 20822143
TI  - Experimental characterization and computational study of unique C,N-chelated
      lithium dianions.
AB  - The structure of a unique C,N-chelated dilithio dianion has been established as a
      solvated monomeric species using a combination of NMR and computational
      techniques. The highly ordered structure of the dianion may be important in its
      reactivity in an oxidative C-N bond-forming process.

PMID- 20822144
TI  - Characterization of phenolics content and antioxidant activity of different beer
      types.
AB  - Despite the wide literature describing the biological effects of polyphenols,
      scarce data are available on their content in the human diet. This study examined
      total polyphenols content, free and total phenolic acids profile, and antioxidant
      activity of different commercial beers types (abbey, ale, bock, wheat, lager,
      pilsner, and dealcoholized). Ferulic acid is by far the most abundant phenolic
      acid in beers, followed by sinapic, vanillic, caffeic, p-coumaric, and 4
      hydroxyphenylacetic acids. Ferulic, caffeic, syringic, sinapic, and, to a lesser
      extent, vanillic acids are present in beers mainly as bound forms, whereas p
      coumaric and 4-hydroxyphenylacetic acids are generally present equally in free
      and bound forms. Total polyphenols and phenolic acids contents greatly vary among
      different beer types (i.e., total polyphenols, from 366 MUg/mL gallic acid
      equivalents for dealcoholized beers to 875 MUg/mL gallic acid equivalents for
      bock beers, with higher values measured in bock, abbey, and ale beers and lower
      values in dealcoholized beers). Similarly, the antioxidant activity measured with
      the ferric reducing antioxidant power (FRAP) assay is remarkably different
      depending on beer type (from 1525 MUM for dealcoholized beers to 4663 MUM for
      bock beers), with higher values in bock, abbey, and ale beers and lower values in
      dealcoholized beers. FRAP values strictly correlate with polyphenols and phenolic
      acids content. The contribution of single phenolic acids to the antioxidant
      activity measured with FRAP assay was also studied.

PMID- 20822145
TI  - Characterization of a thermophilic L-rhamnose isomerase from
      Thermoanaerobacterium saccharolyticum NTOU1.
AB  - L-rhamnose isomerase (EC 5.3.1.14, L-RhI) catalyzes the reversible aldose-ketose
      isomerization between L-rhamnose and L-rhamnulose. In this study, the L-Rhi gene
      encoding L-Rhi was PCR-cloned from Thermoanaerobacterium saccharolyticum NTOU1
      and then expressed in Escherichia coli. A high yield of the active L-RhI, 9780
      U/g of wet cells, was obtained in the presence of 0.2 mM IPTG induction. L-RhI
      was purified sequentially using heat treatment, nucleic acid precipitation, and
      anion-exchange chromatography. The purified L-RhI showed an apparent optimal pH
      of 7 and an optimal temperature at 75  degrees C. The enzyme was stable at pH
      values ranging from 5 to 9, and the activity was fully retained after a 2 h
      incubation at 40-70  degrees C. L-RhI from T. saccharolyticum NTOU1 is the most
      thermostable L-RhI to date, and it has a high specific activity (163 U/mg) and an
      acceptable purity after heat treatment, suggesting that this enzyme has the
      potential to be used in rare sugar production.

PMID- 20822146
TI  - Stereospecific Suzuki-Miyaura coupling of chiral alpha-(acylamino)benzylboronic
      esters with inversion of configuration.
AB  - The first invertive B-alkyl Suzuki-Miyaura coupling has been achieved. The
      coupling of enantioenriched alpha-(acylamino)benzylboronic esters with aryl
      bromides and chlorides took place efficiently in toluene at 80  degrees C in the
      presence of Pd(dba)(2) (5 mol %), XPhos (10 mol %), K(2)CO(3) (3 equiv), and
      H(2)O (2 equiv). The reaction proceeded with inversion of configuration to give
      diarylmethanamine derivatives in high yields with high conservation of
      enantiomeric excesses.

PMID- 20822147
TI  - Coherent interfaces between crystals in nanocrystal composites.
AB  - Numerous materials are polycrystalline or consist with crystals of different
      phases. However, materials consisting of crystals on the nanometer scale
      (nanocrystals) are not simply aggregates of randomly oriented crystals as is
      generally regarded. We found, that in four different materials that consist of
      nanocrystals of two different phases and were obtained by different approaches,
      the nanocrystals of different phases are combined coherently forming interfaces
      with a close crystallographic registry between adjacent crystals (coherent
      interfaces). The four materials were fabricated by (i) depositing Ag(2)O
      nanoparticles on titanate nanofibers, (ii) phase transition from TiO(2)(B)
      nanofibers to the nanofibers of mixed TiO(2)(B) and anatase phases, (iii)
      dehydration of the single crystal fibril titanate core coated with anatase
      nanocrystals, and (iv) attaching zeolite Y nanocrystals on the surface of
      titanate nanofibers. The finding suggests that preferred orientations and
      coherent interfaces generally exist in nanocrystal systems, and according to our
      results, they are largely unaffected by the fabrication process that was used.
      This is because the preferred orientations require that the engaged crystal
      planes from two connected crystals have the same basal spacing and that the
      crystals can interlock tightly at the atomic level to form thermodynamically
      stable interfaces. Hence it is rational that the preferred orientations and
      coherent interfaces dominant the nanostructures formed between the different
      nanocrystals and play a key role in assembling the composite nanostructures. The
      orientation and interfaces between crystals of different phases in mixed-phase
      materials are extremely difficult to determine. Nonetheless, the thermodynamic
      stability of the coherent interfaces allows us to apply phase-transformation
      invariant line strain theory to predict the preferred orientation (and thus the
      structure of the coherent interfaces). The theoretical predications agree
      remarkably with the transmission electron microscopy (TEM) analysis. This implies
      that we may acquire knowledge of the orientation and the interface structures in
      the mixed-phase materials without TEM measurement, and the knowledge is essential
      for comprehensively understanding properties of the many materials and processes
      that depend on the interfaces.

PMID- 20822148
TI  - Molecular characterization of mungbean (Vigna radiata L.) starch branching enzyme
      I.
AB  - Mungbean (Vigna radiata L. cv. Tainan no. 5) starch branching enzyme I (SBE, EC
      2.4.1.18) cDNA, VrsbeI, was cloned, and its expression was characterized.
      Conserved regions of the family B SBE were used to amplify a full length cDNA of
      2208 bp. Phylogeny was analyzed, and the partial 3D structure and functional
      features were predicted. Catalytic residues were identified in the
      (alpha/beta)(8)-fold, and a unique loop from F365 to F376 between beta3/alpha3
      was located. Gene expression of VrsbeI in seeds during growth showed that the
      transcript appeared from week 1 and increased substantially at week 3-4. It was
      cloned into the pET30 vector and expressed in E. coli BL21(DE3) pLysS cells as a
      soluble recombinant protein. The affinity-purified recombinant VrSBEI exhibited a
      specific activity of 314.6 U/mg as an active enzyme with 114-fold activity
      enrichment from the crude extract.

PMID- 20822149
TI  - The Pt-catalyzed ethylene hydroamination by aniline: a computational
      investigation of the catalytic cycle.
AB  - A full QM DFT study without system simplification and with the inclusion of
      solvation effects in aniline as solvent has addressed the addition of aniline to
      ethylene catalyzed by PtBr(2)/Br(-). The resting state of the catalytic cycle is
      the [PtBr(3)(C(2)H(4))](-) complex (II). A cycle involving aniline activation by
      N-H oxidative addition was found energetically prohibitive. The operating cycle
      involves ethylene activation followed by nucleophilic addition of aniline to the
      coordinated ethylene, intramolecular transfer of the ammonium proton to the metal
      center to generate a 5-coordinate (16-electron) Pt(IV)-H intermediate, and final
      reductive elimination of the PhNHEt product. Several low-energy ethylene
      complexes, namely trans- and cis-PtBr(2)(C(2)H(4))(PhNH(2)) (IV and V) and trans-
      and cis-PtBr(2)(C(2)H(4))(2) (VII and VIII) are susceptible to aniline
      nucleophilic addition to generate zwitterionic intermediates. However, only
      [PtBr(3)CH(2)CH(2)NH(2)Ph](-) (IX) derived from PhNH(2) addition to II is the
      productive intermediate. It easily transfers a proton to the Pt atom to yield
      [PtHBr(3)(CH(2)CH(2)NHPh)](-) (XX), which leads to rate-determining C-H reductive
      elimination through transition state TS(XX-L) with formation of the sigma-complex
      [PtBr(3)(kappa(2):C,H-HCH(2)CH(2)NHPh)](-) (L), from which the product can be
      liberated via ligand substitution by a new C(2)H(4) molecule to regenerate II.
      Saturated (18-electron) Pt(IV)-hydride complexes obtained by ligand addition or
      by chelation of the aminoalkyl ligand liberate the product through higher-energy
      pathways. Other pathways starting from the zwitterionic intermediates were also
      explored (intermolecular N deprotonation followed by C protonation or chelation
      to produce platina(II)azacyclobutane derivatives; intramolecular proton transfer
      from N to C, either direct or assisted by an external aniline molecule) but all
      gave higher-energy intermediates or led to the same rate-determining TS(XX-L).

PMID- 20822150
TI  - Facile synthesis of water-dispersible conducting polymer nanospheres.
AB  - Water-dispersible polypyrrole nanospheres with diameters of less than 100 nm were
      synthesized in high yield without any templates, surfactants, or functional
      dopants by the introduction of 2,4-diaminodiphenylamine as an initiator into a
      reaction mixture of pyrrole monomer, oxidant, and acid. The initiator plays a
      critical role in tailoring the nanostructures of polypyrrole. 2,4
      Diaminodiphenylamine interacts with acid to form cations, which combine with
      various anions to self-assemble resulting in different size nanomicelles. These
      nanomicelles, stabilized by initiator molecules, act as templates to encapsulate
      pyrrole and oxidant leading to the formation of nanospheres during
      polymerization. When smaller acids are used, smaller diameter sphere-like
      polypyrrole nanostructures are obtained. The as-synthesized polypyrrole
      nanospheres can then be used to fabricate highly conducting nitrogen-doped carbon
      nanospheres with controllable sizes of 50-220 nm with monodispersities up to 95%
      after pyrolysis. The size of the carbon nanospheres decreases by 20-30 nm due to
      carbonization when compared to the original polymer nanospheres. The molecular
      structures, morphologies, and electrical properties along with the formation
      mechanism of the polypyrrole and carbon nanospheres are discussed.

PMID- 20822151
TI  - Extract of passion fruit (Passiflora edulis) seed containing high amounts of
      piceatannol inhibits melanogenesis and promotes collagen synthesis.
AB  - The effect of passion fruit, the fruit of Passiflora edulis , on melanin
      inhibition and collagen synthesis was studied using cultured human melanoma and
      fibroblast cells. Passion fruit was divided into three parts, rind (PF-R), pulp
      (PF-P), and seed (PF-S), and each part was extracted using 80% ethanol. The
      concentration of polyphenols was higher in PF-S than in PF-R or PF-P. Treatment
      of melanoma cells with PF-S led to inhibition of melanogenesis. In addition, the
      production of total soluble collagen was elevated in dermal fibroblast cells
      cultured in the presence of PF-S. PF-R and PF-P did not yield these effects.
      Furthermore, the removal of polyphenols from PF-S led to the abolishment of the
      effects described above. We discovered that piceatannol (3,4,3',5'-tetrahydroxy
      trans-stilbene) is present in passion fruit seeds in large amounts and that this
      compound is the major component responsible for the PF-S effects observed on
      melanogenesis and collagen synthesis. 

PMID- 20822154
TI  - O-silylative Passerini reaction: a new one-pot synthesis of alpha-siloxyamides.
AB  - A new method for the highly effective synthesis of alpha-siloxyamides is
      described. The addition of isocyanide to aldehyde proceeded smoothly in the
      presence of silanol to give the corresponding alpha-siloxyamides in high yields.
      A wide range of aldehydes and isocyanides are applicable in this reaction.

PMID- 20822153
TI  - A direct intramolecular C-H amination reaction cocatalyzed by copper(II) and
      iron(III) as part of an efficient route for the synthesis of pyrido[1,2
      a]benzimidazoles from N-aryl-2-aminopyridines.
AB  - A novel and efficient synthesis of pyrido[1,2-a]benzimidazoles through direct
      intramolecular aromatic C-H amination of N-aryl-2-aminopyridines has been
      developed. The reaction, cocatalyzed by Cu(OAc)(2) and Fe(NO(3))(3).9H(2)O, is
      carried out in DMF under a dioxygen atmosphere. Diversified pyrido[1,2
      a]benzimidazoles containing various substitution patterns are obtained in
      moderate to excellent yields by using this procedure. The results of mechanistic
      studies suggest that a Cu(III)-catalyzed electrophilic aromatic substitution
      (S(E)Ar) pathway is operating in this process. The unique role of iron(III) is
      believed to lie in its ability to facilitate formation of the more electrophilic
      Cu(III) species. In the absence of iron(III), a much less efficient and
      reversible Cu(II)-mediated S(E)Ar process takes place.

PMID- 20822155
TI  - Stereodivergent construction of aminodiols with a CF3 group.
AB  - A stereodivergent synthesis of various 2-amino-1,3-diols and 3-amino-1,2-diols
      from a single intermediate, 2,3-epoxyketones, is described.

PMID- 20822152
TI  - Physiological parameters for oral delivery and in vitro testing.
AB  - Pharmaceutical solid oral dosage forms must undergo dissolution in the intestinal
      fluids of the gastrointestinal tract before they can be absorbed and reach the
      systemic circulation. Therefore, dissolution is a critical part of the drug
      delivery process. The rate and extent of drug dissolution and absorption depend
      on the characteristics of the active ingredient as well as properties of the
      dosage form. Just as importantly, characteristics of the physiological
      environment such as buffer species, pH, bile salts, gastric emptying rate,
      intestinal motility, and hydrodynamics can significantly impact dissolution and
      absorption. While significant progress has been made since 1970 when the first
      compendial dissolution test was introduced (USP apparatus 1), current dissolution
      testing does not take full advantage of the extensive physiologic information
      that is available. For quality control purposes, where the question is one of lot
      to-lot consistency in performance, using nonphysiologic test conditions that
      match drug and dosage form properties with practical dissolution media and
      apparatus may be appropriate. However, where in vitro-in vivo correlations are
      desired, it is logical to consider and utilize knowledge of the in vivo
      condition. This publication critically reviews the literature that is relevant to
      oral human drug delivery. Physiologically relevant information must serve as a
      basis for the design of dissolution test methods and systems that are more
      representative of the human condition. As in vitro methods advance in their
      physiological relevance, better in vitro-in vivo correlations will be possible.
      This will, in turn, lead to in vitro systems that can be utilized to more
      effectively design dosage forms that have improved and more consistent oral
      bioperformance.

PMID- 20822156
TI  - Sulfur donor atom effects on copper(I)/O(2) chemistry with thioanisole containing
      tetradentate N(3)S ligand leading to MU-1,2-peroxo-dicopper(II) species.
AB  - To better understand the effect of thioether coordination in copper-O(2)
      chemistry, the tetradentate N(3)S ligand L(ASM) (2-(methylthio)-N,N-bis((pyridin
      2-yl)methyl)benzenamine) and related alkylether ligand L(EOE) (2-ethoxy-N,N
      bis((pyridin-2-yl)methyl)ethanamine) have been studied. The corresponding
      copper(I) complexes, [(L(ASM))Cu(I)](+) (1a) and [(L(EOE))Cu(I)](+) (3a), were
      studied as were the related compound [(L(ESE))Cu(I)](+) (2a, L(ESE) = (2
      ethylthio-N,N-bis((pyridin-2-yl)methyl)ethanamine). The X-ray structure of 1a and
      its solution conductivity reveal a monomeric molecular structure possessing
      thioether coordination which persists in solution. In contrast, the C-O
      stretching frequencies of the derivative Cu(I)-CO complexes reveal that for these
      complexes, the modulated ligand arms, whether arylthioether, alkylthioether, or
      ether, are not coordinated to the cuprous ion. Electrochemical data for 1a and 2a
      in CH(3)CN and N,N-dimethylformamide (DMF) show the thioanisole moiety to be a
      poor electron donor compared to alkylthioether (1a is ~200 mV more positive than
      2a). The structures of [(L(ASM))Cu(II)(CH(3)OH)](2+) (1c) and
      [(L(ESE))Cu(II)(CH(3)OH)](2+) (2c) have also been obtained and indicate nearly
      identical copper coordination environments. Oxygenation of 1a at reduced
      temperature gives a characteristic deep blue intermediate
      [{(L(ASM))Cu(II)}(2)(O(2)(2-))](2+) (1b(P)) with absorption features at 442
      (1,500 M(-1) cm(-1)), 530 (8,600 M(-1) cm(-1)), and 605 nm (10,400 M(-1) cm(-1));
      these values compare well to the ligand-to-metal charge-transfer (LMCT)
      transitions previously reported for [{(L(ESE))Cu(II)}(2)(O(2)(2-))](2+) (2b(P)).
      Resonance Raman data for [{(L(ASM))Cu(II)}(2)(O(2)(2-))](2+) (1b(P)) support the
      formation of MU-1,2-peroxo species nu(O-O) = 828 cm(-1)(Delta((18)O(2)) = 48),
      nu(sym)(Cu-O) = 547 cm(-1) (Delta((18)O(2)) = 23), and nu(asym)(Cu-O) = 497 cm(
      1) (Delta((18)O(2)) = 22) and suggest the L(ASM) ligand is a poorer electron
      donor to copper than is L(ESE). In contrast, the oxygenation of
      [(L(EOE))Cu(I)](+) (3a), possessing an ether donor as an analogue of the
      thioether in L(ESE), led to the formation of a bis(MU-oxo) species
      [{(L(EOE))Cu(III)}(2)(O(2-))(2)](2+) (3b(O); 380 nm, epsilon ~ 10,000 M(-1) cm(
      1)). This result provides further support for the sulfur influence in 1b(P) and
      2b(P), in particular coordination of the sulfur to the Cu. Thermal decomposition
      of 1b(P) is accompanied by ligand sulfoxidation. The structure of
      [{(L(EOE))Cu(II)(Cl)}(2)](+) (3c) generated from the reductive dehalogenation of
      organic chlorides suggests that the ether moiety is weakly bound to the cupric
      ion. A detailed discussion of the spectroscopic and structural characteristics of
      1b(P), 2b(P), and 3b(O) is presented.

PMID- 20822157
TI  - Decoupling feature size and functionality in solution-processed, porous hematite
      electrodes for solar water splitting.
AB  - We introduce a simple solution-based strategy to decouple morphological and
      functional effects of annealing nanostructured, porous electrodes by
      encapsulation with a SiO(2) confinement scaffold before high temperature
      treatment. We demonstrate the effectiveness of this approach using porous
      hematite (alpha-Fe(2)O(3)) photoanodes applied for the storage of solar energy
      via water splitting and show that the feature size and electrode functionality
      due to dopant activation can be independently controlled. This allows a
      significant increase in water oxidation photocurrent from 1.57 mA cm(-2) (in the
      control case) to 2.34 mA cm(-2) under standard illumination conditions in 1 M
      NaOH electrolyte-the highest reported for a solution-processed hematite
      photoanode. This increase is attributed to the improved quantum efficiency,
      especially with longer wavelength photons, due to a smaller particle size, which
      is afforded by our encapsulation strategy.

PMID- 20822158
TI  - Kinetic analysis of the bisubstrate cysteine desulfurase SufS from Bacillus
      subtilis.
AB  - Cysteine is the major sulfur donor for thio cofactors in bacterial and eukaryotic
      systems. The first step in sulfur mobilization involves a PLP-dependent enzymatic
      mechanism. During catalysis, free cysteine is converted into alanine with the
      concomitant formation of a persulfide bond with the catalytic cysteine residue,
      thus forming a covalent enzyme intermediate. Cysteine desulfurases in their
      persulfurated forms serve as donors at the intersection of various cellular
      sulfur-requiring pathways. Most Gram-positive bacteria, including Bacillus
      subtilis, contain a cysteine desulfurase gene sufS located adjacent to the gene
      encoding the proposed Fe-S cluster scaffold SufU. In this work, we identified the
      participation of SufU as a substrate in the SufS catalytic mechanism. Development
      of a sensitive method for detection of alanine formed in the SufS reaction
      enabled the identification of its associated mechanistic features. Steady-state
      kinetic analysis of alanine formation provided evidence of a double-displacement
      mechanism (ping-pong) of the cysteine:SufU sulfurtransferase reaction catalyzed
      by SufS. Results from site-directed mutagenesis of the catalytic cysteine
      (SufS(C361A)) and iodoacetamide alkylation of SufU support the occurrence of
      persulfide sulfur transfer steps in the mechanism of SufS.

PMID- 20822159
TI  - Quantum dot peptide biosensors for monitoring caspase 3 proteolysis and calcium
      ions.
AB  - The nanoscale size and unique optical properties of semiconductor quantum dots
      (QDs) have made them attractive as central photoluminescent scaffolds for a
      variety of biosensing platforms. In this report we functionalize QDs with dye
      labeled peptides using two different linkage chemistries to yield Forster
      resonance energy transfer (FRET)-based sensors capable of monitoring either
      enzymatic activity or ionic presence. The first sensor targets the proteolytic
      activity of caspase 3, a key downstream effector of apoptosis. This QD conjugate
      utilized carbodiimide chemistry to covalently link dye-labeled peptide substrates
      to the terminal carboxyl groups on the QD's surface hydrophilic ligands in a
      quantitative manner. Caspase 3 cleaved the peptide substrate and disrupted QD
      donor-dye acceptor FRET providing signal transduction of enzymatic activity and
      allowing derivation of relevant Michaelis-Menten kinetic descriptors. The second
      sensor was designed to monitor Ca2+ ions that are ubiquitous in many biological
      processes. For this sensor, Cu+-catalyzed [3 + 2] azide-alkyne cycloaddition was
      exploited to attach a recently developed azide-functionalized CalciumRuby-Cl
      indicator dye to a cognate alkyne group present on the terminus of a modified
      peptide. The labeled peptide also expressed a polyhistidine sequence, which
      facilitated its subsequent metal-affinity coordination to the QD surface
      establishing the final FRET sensing construct. Adding exogenous Ca2+ to the
      sensor solution increased the dyes fluorescence, altering the donor-acceptor
      emission ratio and manifested a dissociation constant similar to that of the
      native dye. These results highlight the potential for combining peptides with QDs
      using different chemistries to create sensors for monitoring chemical compounds
      and biological processes.

PMID- 20822160
TI  - Ultrasonic detector for high precision measurements of carbon dioxide.
AB  - A new instrument for monitoring atmospheric CO(2) has been developed based on the
      measurement of the speed of sound in air. The instrument uses a selective
      scrubber to yield highly precise and accurate measurements of CO(2) mixing ratios
      at ambient concentrations. The instrument has a precision of 0.3 ppmv (1sigma)
      with a signal that is independent of pressure and requires a flow rate of only 30
      mL/min. Laboratory measurements of atmospheric CO(2) showed excellent agreement
      with values obtained by nondispersive infrared absorption. The instrument has the
      advantage of collecting continuous, high-precision data every 25 s and can be
      modified for vertical profiling studies using kites, balloons, or light aircraft
      for the purpose of measuring landscape-scale fluxes.

PMID- 20822162
TI  - Single-, few-, and multilayer graphene not exhibiting significant advantages over
      graphite microparticles in electroanalysis.
AB  - This report compares the electroanalytical performances of single- (G-SL), few-
      (G-FL), and multilayer graphene (G-ML), graphite microparticles, and edge-plane
      pyrolytic graphite electrodes in terms of sensitivity, linearity, and
      repeatability. We show that in the case of differential pulse voltammetric (DPV)
      detection of ascorbic acid, the sensitivity of a G-SL electrode is about 30%
      greater than that of G-ML and about 40% greater than graphite microparticles.
      However, in the case of DPV determination of uric acid, sensitivity is
      practically the same for all (G-SL, G-FL, and G-ML) and, importantly, the
      graphite microparticles do provide higher sensitivity than graphenes do for this
      analyte. Graphenes also do not provide a significant advantage in terms of
      repeatability. We pose the question of whether the efforts leading to the bulk
      method of producing single-layer graphene are justified for electroanalytical
      applications.

PMID- 20822161
TI  - Species differences in the pharmacology and toxicology of PEGylated helper
      dependent adenovirus.
AB  - Clinically relevant doses of helper-dependent adenoviruses (HDAds) provoke the
      host response against capsid proteins in primates and rodents. To determine if
      PEGylation truly affects this, baboons and mice were given either HDAd or PEG
      HDAd expressing beta-galactosidase at 5 * 1011 or 3 * 1012 virus particles per
      kilogram (vp/kg) by iv infusion. Serum cytokines and blood chemistries were
      assessed for 96 h. PEG-HDAd reduced IL-6 6-fold in mice and 3-fold in the
      primate. This vector reduced IL-12 by 50% in both animal models. PEGylation
      reduced serum transaminases by approximately 50% at each dose in the primate and
      the mouse. PEGylation did not alter hepatic transduction efficiency in the mouse
      but did reduce transduction efficiency in the liver and the spleen of primates.
      Unmodified and PEGylated virus suppressed hepatic CYP3A activity in both animal
      models. PEGylation doubled the half-life (t(1/2)) of the virus in the mouse and
      cut plasma clearance (CL) in half without affecting the half-life in primates.
      These results suggest that there are notable species-specific differences in the
      biodistribution of and response to PEG-modified vectors which may be linked to
      differences in binding properties to coagulation factors, receptor density and
      tissue architecture in the liver.

PMID- 20822163
TI  - Structure and "surfactochromic" properties of conjugated polyelectrolyte (CPE):
      surfactant complexes between a cationic polythiophene and SDS in water.
AB  - We report on the phase transitions, solution structure, and consequent effect on
      the photophysical properties of poly[3-(6-trimethylammoniumhexyl)thiophene]
      bromide (P3TMAHT) in aqueous sodium dodecylsulfate (SDS). Polythiophene was mixed
      with SDS or deuterated SDS to form P3TMAHT(SDS)(x) complex (x = the molar ratio
      of surfactant over monomer units) in D(2)O and studied by small-angle neutron and
      X-ray scattering (SANS/SAXS) and optical spectroscopy. At room temperature,
      P3TMAHT forms charged aggregates with interparticle order. The addition of SDS
      eliminates the interparticle order and leads to rod-like (x = 1/5) or sheet-like
      polymer-SDS aggregates (x = 1/2 to 1) containing rod-like (x = 1/5 to 1/2) or
      sheet-like (x = 1/2 to 1) polymer associations. Partial precipitation occurs at
      the charge compensation point (x = 1). Ellipsoidal particles without
      interparticle order, reminiscent of SDS micelles modified by separated polymer
      chains, occur for x = 2 to 5. Free SDS micelles dominate for x = 20. Structural
      transitions lead to a concomitant variation in the solution color from red
      (P3TMAHT) to violet (x = 1/5 to 1) to yellow (x > 2). The photoluminescence
      fingerprint changes progressively from a broad featureless band (x = 0) through
      the band narrowing and appearance of vibronic structure (x = 1/5 to 1) to the
      return to a blue-shifted broad emission band (x = 5). The polymer stiffness
      reaches a maximum for x = 1, which leads to minimization of the Stokes shift
      (0.08 eV). This work gives fundamental information upon how surfactant
      complexation can influence both the solution structure and photophysical
      properties of a water-soluble polythiophene.

PMID- 20822164
TI  - Microfluidic serial dilution cell-based assay for analyzing drug dose response
      over a wide concentration range.
AB  - In this paper we report a perfusion culture microchamber array chip with a serial
      dilution microfluidic network for analyzing drug dose response over a
      concentration range spanning 6 orders of magnitude, which is required for
      practical drug discovery applications. The microchamber array chip was equipped
      with a pressure-driven interface, in which medium and drug solution were added
      with a micropipet and delivered into the microfluidic network by pneumatic
      pressure. We demonstrated that the microchamber array chip could be used to
      estimate the 50% growth inhibitory concentration using the model anticancer drug
      paclitaxel and the model cancer cell line HeLa. The results obtained by using the
      microchamber array chip were consistent with those obtained by a conventional
      assay using microplates. The microchamber array chip, with its simple interface
      and well-designed microfluidic network, has potential as an efficient platform
      for high-throughput dose response assays in drug discovery applications.

PMID- 20822165
TI  - Effects of multibranching on 3-hydroxyflavone-based chromophores and the excited
      state intramolecular proton transfer dynamics.
AB  - A series of one-, two-, and three-branched chromophores based on 3
      hydroxyflavones (1-3) have been synthesized as the first example of multibranched
      chromophores demonstrating excited-state intramolecular proton transfer (ESIPT).
      Coupling between the 3-hydroxyflavone branches connected by an electron-donating
      triphenylamine core is manifested in the red-shifted and asymmetric absorption
      band of 2, whereas the absorption of 3 is governed by the divided donor strength.
      Their excited-state charge-transfer (ESCT)-coupled ESIPT dynamics is investigated
      via femtosecond fluorescence upconversion and is proved to be well correlated
      with the ratio of normal/tautomer emission in the fluorescence spectra. For 1 and
      2, with increased donor strength compared with the 4'-N,N-dialkylamino-3
      hydroxyflavone analogue, ESIPT appears to cease in the more polar solvent of
      acetonitrile. Nevertheless, similar dependence of 1-3 on solvent polarity
      signifies resembling charge-transfer character at the normal excited states (N*),
      despite their varying structures. As evidenced by the theoretical approach, the
      frontier orbitals of vibrationally relaxed (geometry-optimized) N*, from which
      fluorescence and ESIPT should take place, are localized on one specific branch,
      leading to similar emission patterns and dynamics, whereas the orbitals
      contributing to Franck-Condon excitation (absorption) spread over the entire
      molecule. The localization is found to be facilitated by rotation of a specific
      branch pivoting on the central nitrogen atom, while planarity is maintained
      within each 3-hydroxyflavone chromophore.

PMID- 20822166
TI  - Quantitative determination of biogenic volatile organic compounds in the
      atmosphere using proton-transfer reaction linear ion trap mass spectrometry.
AB  - Although oxidation of biogenic volatile organic compounds (BVOCs) plays an
      important role in tropospheric ozone and secondary organic aerosol production,
      significant uncertainties remain in our understanding of the impacts of BVOCs on
      ozone, aerosols, and climate. To quantify BVOCs, the proton-transfer reaction
      linear ion trap (PTR-LIT) mass spectrometer was previously developed. The PTR-LIT
      represents an improvement over more traditional techniques (including the proton
      transfer reaction mass spectrometer), providing the capability to directly
      quantify and differentiate isomeric compounds by MS/MS analysis, with better time
      resolution and minimal sample handling, compared to gas chromatography
      techniques. Herein, we present results from the first field deployment of the PTR
      LIT. During the Program for Research on Oxidants: Photochemistry, Emissions and
      Transport (PROPHET) summer 2008 study in northern Michigan, the PTR-LIT
      successfully quantified isoprene, total monoterpenes, and isomeric isoprene
      oxidation products methyl vinyl ketone and methacrolein at sub-parts per billion
      (nmol/mol) levels in a complex forest atmosphere. The utility of the fast time
      response of the PTR-LIT was shown by the measurement of rapid changes in
      isoprene, methyl vinyl ketone, and methacrolein, concurrent with changing ozone
      mole fractions. Overall, the PTR-LIT was shown to be a viable field instrument
      with the necessary sensitivity, selectivity, and time response to provide
      detailed measurements of BVOC mole fractions in complex atmospheric samples, at
      trace levels.

PMID- 20822167
TI  - Spontaneous formation of periodic nanostructures by localized dynamic wrinkling.
AB  - Micro/nanoscale periodic structures are widely used in display, optics and bio
      industries as key functional elements. We present a novel nanopatterning method,
      localized dynamic wrinkling (LDW), which creates micro/nanoscale metal gratings
      continuously by simply sliding a flat edge of a hard material over a thin metal
      surface coated on a polymer layer. The LDW process presented in this paper is an
      etching- and template-free nanopatterning technology based on nanoscale wrinkling
      phenomenon. This simple process enables spontaneous formation of large-area metal
      gratings with controllable periodicity from micrometer down to 120 nm.

PMID- 20822168
TI  - Nanotheranostics and image-guided drug delivery: current concepts and future
      directions.
AB  - Nanomedicine formulations aim to improve the biodistribution and the target site
      accumulation of systemically applied (chemo-) therapeutics. Various different
      passively and actively targeted nanomedicines have been evaluated over the years,
      based e.g. on liposomes, polymers, micelles and antibodies, and a significant
      amount of (pre-) clinical evidence has been obtained showing that these 5-200 nm
      sized carrier materials are able to improve the therapeutic index of low
      molecular-weight drugs. Besides for therapeutic purposes, however, nanomedicine
      formulations have also been more and more used for imaging applications, as well
      as, in recent years, for theranostic approaches, i.e. for systems and strategies
      in which disease diagnosis and therapy are combined. Potential applications of
      theranostic nanomedicine formulations range from the noninvasive assessment of
      the biodistribution and the target site accumulation of low-molecular-weight
      drugs, and the visualization of drug distribution and drug release at the target
      site, to the optimization of strategies relying on triggered drug release, and
      the prediction and real-time monitoring of therapeutic responses. Nanotheranostic
      systems are consequently considered to be highly suitable systems for (pre-)
      clinical implementation, not only because they might assist in better
      understanding various important aspects of the drug delivery process, and in
      developing better drug delivery systems, but also because they might contribute
      to realizing the potential of "personalized medicine", and to developing more
      effective and less toxic treatment regimens for individual patients.

PMID- 20822169
TI  - Phenylene bridged boron-nitrogen containing dendrimers.
AB  - The synthesis and characterization of novel phenylene bridged boron-nitrogen
      containing pi-conjugated dendrimers N3B6 and N3B3, with peripheral boron atoms
      and 1,3,5-triaminobenzene moiety as a core, are presented. UV-vis absorption and
      emission measurements reveal that the optical properties of the resulting
      compounds can be controlled by changing the donor/acceptor ratio: a 1:1 ratio
      results in a more efficient charge transfer than the 1:2 ratio. This was proven
      by the red shift of the emission maxima and the stronger solvatochromic effect in
      N3B3 compared to N3B6.

PMID- 20822170
TI  - Development of bifunctional aza-bis(oxazoline) copper catalysts for
      enantioselective Henry reaction.
AB  - Base-functionalized aza-bis(oxazoline) ligands were prepared to explore the
      concept of dual activation through the Lewis acid and a tethered tertiary amine
      base. The catalytic activity of the Cu complex was evaluated for the asymmetric
      Henry reaction. Compared with a corresponding unfunctionalized copper complex
      with external 1-benzyl-4-ethylpiperazine base, the ethylpiperazine-functionalized
      aza-bis(oxazoline) copper catalyst resulted in rate acceleration (2.5 times) as
      well as improved enantioselectivity (72% ee vs 92% ee).

PMID- 20822171
TI  - High yield synthesis of pure alkanethiolate-capped silver nanoparticles.
AB  - One-phase, one-pot synthesis of Ag(0) nanoparticles capped with alkanethiolate
      molecules has been optimized to easily achieve a pure product in quantitative
      yield. We report the synthesis of dodecanethiolate-capped silver particles and
      the chemophysical, structural, and morphologic characterization performed by way
      of UV-vis, (1)H NMR, and X-ray photoelectron (XPS) spectroscopies, X-ray powder
      diffraction (XRD) and X-ray absorption fine structure analysis (XFAS), electron
      diffraction and high-resolution transmission electron microscopy (HR-TEM), and
      scanning and transmission electron microscopy (SEM and TEM). Depending on the
      molar ratio of the reagents (dodecylthiosulphate/Ag(+)), the mean Ag(0) particle
      size D(XRD) is tuned from 4 to 3 nm with a narrow size distribution. The
      particles are highly soluble, very stable in organic solvents (hexane, toluene,
      dichloromethane, etc.), and resistant to oxidation; the hexane solution after one
      year at room temperature does not show any precipitation or formation of
      oxidation byproducts.

PMID- 20822172
TI  - An asymmetric hydrogenation route to (-)-spongidepsin.
AB  - (-)-Spongidepsin 1, a cytotoxic marine natural product, was prepared via two
      iridium-catalyzed hydrogenation reactions; both were highly stereoselective,
      giving convenient access to pivotal intermediates. This synthesis was modified to
      give several spongidepsin analogues, and their cytotoxicities were compared with
      those of the natural product.

PMID- 20822173
TI  - Three-metal coordination by novel bisporphyrin architectures.
AB  - The synthesis and characterization of a new type of bisporphyrin system is
      reported where the two macrocycles are linked in a cofacial arrangement by a
      substituted carbazole bridge. The three nitrogen atoms of the carbazole bridge in
      the compounds may complex a metal ion and thus provide a new parameter for
      varying the physical properties and flexibility of the dyad after formation of a
      three-metal system. In the present study, four bis-metalloporphyrin complexes
      were synthesized and examined by electrochemistry and thin-layer
      spectroelectrochemistry in CH(2)Cl(2) and PhCN. Two of the examined compounds
      contain Cu(II) or Zn(II) porphyrins and a carbazole linker with a bound Cu(II)
      ion, giving a three metal system, while the other two examined compounds
      contained the same porphyrins but with a carbazole bridge which lacks the Cu(II)
      component. Since carbazoles and Cu(II) ions are both electroactive, redox
      properties of several unlinked carbazoles with and without bound Cu(II) ions were
      also examined as to their electrochemical behavior under the same solution
      conditions as the dyads to better understand the redox reactions which may occur
      at the carbazole group linking the two porphyrin macrocycles. Several mononuclear
      porphyrins with structures related to macrocycles in the dyads were also
      investigated.

PMID- 20822174
TI  - Distinct cell responses to substrates consisting of poly(epsilon-caprolactone)
      and poly(propylene fumarate) in the presence or absence of cross-links.
AB  - To investigate the role of chemical cross-links in regulating biomaterial
      properties and cell behavior, we have prepared and characterized a series of
      biodegradable polymer blends in both un-cross-linked and photo-cross-linked
      forms. In this comparative study, these blends consisted of an oligomeric, cross
      linkable, amorphous poly(propylene fumarate) (PPF) and a high-molecular-weight,
      semicrystalline poly(epsilon-caprolactone) (PCL). After cross-linking, semi
      interpenetrating polymer networks (semi-IPNs) were formed by combining PPF
      chemical network and PCL physical network that was associated by the
      crystallites. The material design strategy presented here was different from
      previously studied semicrystalline polymer networks, in which crystallizable
      segments participated covalently in the chemical network and were significantly
      suppressed by the network. For these PPF/PCL blends, thermal properties such as
      melting temperature (T(m)) and crystallinity have been correlated with their
      rheological and mechanical properties to demonstrate the effects of cross-linking
      density and crystallinity. Surface morphology, hydrophilicity, and the capability
      of adsorbing proteins from cell culture media have also been determined. For
      potential applications in bone and vascular tissue engineering and demonstration
      of regulating cell behavior on polymer substrates with controllable
      physicochemical characteristics, in vitro cell studies that included cell
      viability, attachment, spreading, and proliferation have been performed using
      mouse MC3T3 cells and primary rat aortic smooth muscle cells (SMCs). In a similar
      manner, these two cell types have been found to show distinct cell responses to
      the polymer substrates in the presence or absence of cross-links.

PMID- 20822175
TI  - Interplay between secondary and tertiary structure formation in protein folding
      cooperativity.
AB  - Protein folding cooperativity is defined by the nature of the finite-size
      thermodynamic transition exhibited upon folding: two-state transitions show a
      free-energy barrier between the folded and unfolded ensembles, while downhill
      folding is barrierless. A microcanonical analysis, where the energy is the
      natural variable, has proved to be better suited than its canonical counterpart
      to unambiguously characterize the nature of the transition. Replica-exchange
      molecular dynamics simulations of a high-resolution coarse-grained model allow
      for the accurate evaluation of the density of states in order to extract precise
      thermodynamic information and measure its impact on structural features. The
      method has been applied to three helical peptides: a short helix shows sharp
      features of a two-state folder, while a longer helix and a three-helix bundle
      exhibit downhill and two-state transitions, respectively. Extending the results
      of lattice simulations and theoretical models, we have found that it is the
      interplay between secondary structure and the loss of non-native tertiary
      contacts that determines the nature of the transition.

PMID- 20822176
TI  - The stabilizing effect of silicate on biogenic and synthetic amorphous calcium
      carbonate.
AB  - Silicate ions increase the thermal stability of the unstable amorphous calcium
      carbonate (ACC). This effect was observed first by comparing ACC from two
      different species of cystoliths, small calcified bodies formed in the leaves of
      some plants. The temperature of crystallization to calcite in the silicate-rich
      cystoliths from M. alba is 100  degrees C higher than that of the silicate-poor
      cystoliths from F. microcarpa. The stabilizing effect is confirmed in vitro with
      synthetic samples differing in their silicate content. With increasing silicate
      concentration in ACC, the crystallization temperature to calcite also increases.
      A mechanism of geometric frustration is suggested, whereby the presence of the
      tetrahedral silicate ion in the flat carbonate lattice prevents organization into
      crystalline polymorphs.

PMID- 20822177
TI  - Synthesis of isoflavone aglycones and equol in soy milks fermented by food
      related lactic acid bacteria and their effect on human intestinal Caco-2 cells.
AB  - One hundred and three strains of lactic acid bacteria, isolated from various food
      ecosystems, were assayed for beta-glucosidase activity toward p-nitrophenyl-beta
      D-glucopyranoside substrate. Lactobacillus plantarum DPPMA24W and DPPMASL33,
      Lactobacillus fermentum DPPMA114, and Lactobacillus rhamnosus DPPMAAZ1 showed the
      highest activities and were selected as the mixed starter to ferment various soy
      milk preparations, which mainly differed for chemical composition, protein
      dispersibility index, and size dimension. The soy milk made with organically
      farmed soybeans (OFS) was selected as the best preparation. All selected strains
      grew well in OFS soy milk, reaching almost the same values of cell density (ca.
      8.5 log cfu/mL). After 96 h of fermentation with the selected mixed starter, OFS
      soy milk contained 57.0 MUM daidzein, 140.3 MUM genistein, 20.4 MUM glycitein,
      and 37.3 MUM equol. Fermented and nonfermented OFS soy milks were used for the in
      vitro assays on intestinal human Caco-2/TC7 cells. Fermented OFS soy milk
      markedly inhibited the inflammatory status of Caco-2/TC7 cells as induced by
      treatment with interferon-gamma (IFN-gamma) (1000 U/mL) and lipopolysaccharide
      (LPS) (100 ng/mL), maintained the integrity of the tight junctions, even if
      subjected to negative stimulation by IFN-gamma, and markedly inhibited the
      synthesis of IL-8, after treatment with interleukin-1beta (2 ng/mL). As shown by
      using chemical standards, these effects were due to the concomitant activities of
      isoflavone aglycones and, especially, equol, which were synthesized in the
      fermented OFS soy milk preparation.

PMID- 20822178
TI  - Curcuminoids suppress the growth and induce apoptosis through caspase-3-dependent
      pathways in glioblastoma multiforme (GBM) 8401 cells.
AB  - Curcuminoids, natural plant components, have been recently shown to display
      antioxidant and anti-inflammatory activities. They also produce potent chemo
      preventive action against several types of cancer. In the present study, the anti
      proliferative and induced apoptosis effects of curcuminoids have been
      investigated in human brain glioblastoma multiforme (GBM) 8401 cells. Results
      indicated that curcuminoids have produced an inhibition of cell proliferation in
      a dose-dependent manner as dosage increased from 12.5 to 100 MUM (n = 6) via the
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as well
      as activation of apoptosis in GBM 8401 cells. Both effects were observed to
      increase in proportion with the dose of curcuminoids. We have studied the
      mitochondrial membrane potential (DeltaPsim), DNA fragmentation, caspase-3,
      caspase-8, and caspase-9 activation, and nuclear factor kappaB (NF-kappaB)
      transcriptional factor activity to analyze apoptosis in GBM 8401 cells. From
      these approaches, apoptosis was induced by curcuminoids in human brain GBM 8401
      cells via mitochondria and a caspase-dependent pathway. The results observed with
      proliferation inhibition (y = 94.694e(-0.025x), R(2) = 0.9901, and n = 6) and
      apoptosis (y = 0.9789e(-0.0102x), R(2) = 0.99854, and n = 3) depend upon the
      amount of curcuminoid treatment in the cancer cells.

PMID- 20822179
TI  - A lead(II)-driven DNA molecular device for turn-on fluorescence detection of
      lead(II) ion with high selectivity and sensitivity.
AB  - A Pb(2+)-driven DNA molecular device which is constructed based on a DNA duplex
      quadruplex exchange is utilized for the highly selective and sensitive detection
      of Pb(2+). The power of this DNA device originates from the excellent efficiency
      of Pb(2+) for stabilizing G-quadruplexes, which makes the DNA duplex unwind
      thereby driving the device. This device can be reset to the original state by
      addition of a strong Pb(2+) chelator DOTA, endowing the device with good
      reusability. In the whole process, the signal readout is modulated via a
      fluorescent probe binding to and being released from the G-quadruplex. Such a DNA
      device can serve as a novel turn-on fluorescent sensor for Pb(2+) detection with
      high selectivity and sensitivity.

PMID- 20822180
TI  - Conformational space of flexible biological macromolecules from average data.
AB  - The concept of maximum occurrence (MO), i.e., the maximum percent of time that
      flexible proteins can spend in any given conformation, is introduced, and a
      rigorous method is developed to extensively sample the conformational space and
      to construct MO maps from experimental data. The method is tested in a case
      study, the flexible two-domain protein calmodulin (CaM), using SAXS and NMR data
      (i.e., pseudocontact shifts and self-orientation residual dipolar couplings
      arising from the presence of paramagnetic lanthanide ions), revealing that the
      "closed" and "fully extended" conformations trapped in the crystalline forms of
      CaM have MOs of only 5 and 15%, respectively. Compact conformations in general
      have small MOs, whereas some extended conformations have MO as high as 35%,
      strongly suggesting these conformations to be most abundant in solution. The
      method is universally applicable as it requires only standard SAXS data and
      specific NMR data on lanthanide derivatives of the protein (using native metal
      sites or lanthanide tagging). The computer program is publicly available using
      the grid computing infrastructure through the authors' Web portal.

PMID- 20822181
TI  - Structure-based design and synthesis of potent, ethylenediamine-based, mammalian
      farnesyltransferase inhibitors as anticancer agents.
AB  - A potent class of anticancer, human farnesyltransferase (hFTase) inhibitors has
      been identified by "piggy-backing" on potent, antimalarial inhibitors of
      Plasmodium falciparum farnesyltransferase (PfFTase). On the basis of a 4-fold
      substituted ethylenediamine scaffold, the inhibitors are structurally simple and
      readily derivatized, facilitating the extensive structure-activity relationship
      (SAR) study reported herein. Our most potent inhibitor is compound 1f, which
      exhibited an in vitro hFTase IC(50) value of 25 nM and a whole cell H-Ras
      processing IC(50) value of 90 nM. Moreover, it is noteworthy that several of our
      inhibitors proved highly selective for hFTase (up to 333-fold) over the related
      prenyltransferase enzyme geranylgeranyltransferase-I (GGTase-I). A crystal
      structure of inhibitor 1a co-crystallized with farnesyl pyrophosphate (FPP) in
      the active site of rat FTase illustrates that the para-benzonitrile moiety of 1a
      is stabilized by a pi-pi stacking interaction with the Y361beta residue,
      suggesting a structural explanation for the observed importance of this component
      of our inhibitors.

PMID- 20822182
TI  - Selective C-4 alkylation of pyridine by nickel/Lewis acid catalysis.
AB  - Direct C-4-selective addition of pyridine across alkenes and alkynes is achieved
      for the first time by nickel/Lewis acid cooperative catalysis with an N
      heterocyclic carbene ligand. A variety of substituents on both alkenes and
      pyridine are tolerated to give linear 4-alkylpyridines in modest to good yields.
      The addition across styrene, on the other hand, gives branched 4-alkylpyridines.
      A single example of C-4-selective alkenylation is also described.

PMID- 20822183
TI  - DNA pol lambda's extraordinary ability to stabilize misaligned DNA.
AB  - DNA polymerases have the venerable task of maintaining genome stability during
      DNA replication and repair. Errors, nonetheless, occur with error propensities
      that are polymerase specific. For example, DNA polymerase lambda (pol lambda)
      generates single-base deletions through template-strand slippage within short
      repetitive DNA regions much more readily than does the closely related polymerase
      beta (pol beta). Here we present in silico evidence to help interpret pol
      lambda's greater tendency for deletion errors than pol beta by its more favorable
      protein/DNA electrostatic interactions immediately around the extrahelical
      nucleotide on the template strand. Our molecular dynamics and free energy
      analyses suggest that pol lambda provides greater stabilization to misaligned DNA
      than aligned DNA. Our study of several pol lambda mutants of Lys544 (Ala, Phe,
      Glu) probes the interactions between the extrahelical nucleotide and the adjacent
      Lys544 to show that the charge of the 544 residue controls stabilization of the
      DNA misalignment. In addition, we identify other thumb residues (Arg538, Lys521,
      Arg517, and Arg514) that play coordinating roles in stabilizing pol lambda's
      interactions with misaligned DNA. Interestingly, their aggregate stabilization
      effect is more important than that of any one component residue, in contrast to
      aligned DNA systems, as we determined from mutations of these key residues and
      energetic analyses. No such comparable network of stabilizing misaligned DNA
      exists in pol beta. Evolutionary needs for DNA repair on substrates with minimal
      base-pairing, such as those encountered by pol lambda in the non-homologous end
      joining pathway, may have been solved by a greater tolerance to deletion errors.
      Other base-flipping proteins share similar binding properties and motions for
      extrahelical nucleotides.

PMID- 20822184
TI  - Chemistry and pharmacological characterization of novel nitrogen analogues of
      AMOP-H-OH (Sazetidine-A, 6-[5-(azetidin-2-ylmethoxy)pyridin-3-yl]hex-5-yn-1-ol)
      as alpha4beta2-nicotinic acetylcholine receptor-selective partial agonists.
AB  - In order to advance therapeutic applications of nicotinic ligands, continuing
      research efforts are being directed toward the identification and
      characterization of novel nicotinic acetylcholine receptor (nAChR) ligands that
      are both potent and subtype selective. Herein we report the synthesis and
      pharmacological evaluation of members of a new series of 3-alkoxy-5-aminopyridine
      derivatives that display good selectivity for the alpha4beta2-nAChR subtype based
      on ligand binding and functional evaluations. The most potent ligand in this
      series, compound 64, showed high radioligand binding affinity and selectivity for
      rat alpha4beta2-nAChR with a K(i) value of 1.2 nM and 4700-fold selectivity for
      alpha4beta2- over alpha3beta4-nAChR, and ~100-fold selectivity for functional,
      high-sensitivity, human alpha4beta2-nAChR over alpha3beta4*-nAChR. In the mouse
      forced swim test, compound 64 exhibited antidepressant-like effects. Structure
      activity relationship (SAR) analyses suggest that the introduction of additional
      substituents to the amino group present on the pyridine ring of the N
      demethylated analogue of compound 17 can provide potent alpha4beta2-nAChR
      selective ligands for possible use in treatment of neurological and psychiatric
      disorders including depression.

PMID- 20822185
TI  - Toponome imaging system: in situ protein network mapping in normal and cancerous
      colon from the same patient reveals more than five-thousand cancer specific
      protein clusters and their subcellular annotation by using a three symbol code.
AB  - In a proof of principle study, we have applied an automated fluorescence toponome
      imaging system (TIS) to examine whether TIS can find protein network structures,
      distinguishing cancerous from normal colon tissue present in a surgical sample
      from the same patient. By using a three symbol code and a power of combinatorial
      molecular discrimination (PCMD) of 2(21) per subcellular data point in one single
      tissue section, we demonstrate an in situ protein network structure, visualized
      as a mosaic of 6813 protein clusters (combinatorial molecular phenotype or CMPs),
      in the cancerous part of the colon. By contrast, in the histologically normal
      colon, TIS identifies nearly 5 times the number of protein clusters as compared
      to the cancerous part (32 009). By subcellular visualization procedures, we found
      that many cell surface membrane molecules were closely associated with the cell
      cytoskeleton as unique CMPs in the normal part of the colon, while the same
      molecules were disassembled in the cancerous part, suggesting the presence of
      dysfunctional cytoskeleton-membrane complexes. As expected, glandular and stromal
      cell signatures were found, but interestingly also found were potentially TIS
      signatures identifying a very restricted subset of cells expressing several
      putative stem cell markers, all restricted to the cancerous tissue. The detection
      of these signatures is based on the extreme searching depth, high degree of
      dimensionality, and subcellular resolution capacity of TIS. These findings
      provide the technological rationale for the feasibility of a complete colon
      cancer toponome to be established by massive parallel high throughput/high
      content TIS mapping.

PMID- 20822186
TI  - Mass spectrometric immunoassay for quantitative determination of protein
      biomarker isoforms.
AB  - Protein biomarkers are essential in assessing pathogenic processes. The impetus
      for finding new biomarkers has been accelerated by the arrival of the "omics"
      technologies. However, equally important is the rediscovery of existing
      biomarkers with these new approaches as novel variants can be discovered that can
      improve their utility. Presented here is a mass spectrometric immunoassay method
      for quantitative determination of beta-2-microglobulin, an established biomarker
      used in the diagnosis of active rheumatoid arthritis and kidney disease, and its
      structural variant, cleaved at and deficient in lysine-58 (DeltaK58-b2m). beta
      Lactoglobulin was incorporated into the assay as an internal reference standard,
      serving as normalization point for beta-2-microglobulin quantification. The
      precision, linearity, and recovery characteristics of the assay were established.
      The new assay was also benchmarked against existing beta-2-microglobulin ELISA.
      The assay was utilized to determine the individual concentration of beta-2
      microglobulin and its variant across a larger cohort of samples, demonstrating
      the ability to simultaneously quantify both proteins.

PMID- 20822187
TI  - Quantitative proteomic analysis reveals the perturbation of multiple cellular
      pathways in jurkat-T cells induced by doxorubicin.
AB  - Doxorubicin remains an important part of chemotherapy regimens in the clinic and
      is considered an effective agent in the treatment of acute lymphoblastic leukemia
      (ALL). Although the cellular responses induced by doxorubicin treatment have been
      investigated for years, the precise mechanisms underlying its cytotoxicity and
      therapeutic activity remain unclear. Here we utilized mass spectrometry, together
      with stable isotope labeling by amino acids in cell culture (SILAC), to analyze
      comparatively the protein expression in Jurkat-T cells before and after treatment
      with a clinically relevant concentration of doxorubicin. We were able to quantify
      1066 proteins in Jurkat-T cells with both forward and reverse SILAC measurements,
      among which 62 were with significantly altered levels of expression induced by
      doxorubicin treatment. These included the up-regulation of core histones,
      heterogeneous nuclear ribonucleoproteins, and superoxide dismutase 2 as well as
      the down-regulation of hydroxymethylglutaryl-CoA synthase and farnesyl
      diphosphate synthase. The latter two are essential enzymes for cholesterol
      biosynthesis. We further demonstrated that the doxorubicin-induced growth
      inhibition of Jurkat-T cells could be rescued by treatment with cholesterol,
      supporting that doxorubicin exerts its cytotoxic effect, in part, by suppressing
      the expression of hydroxymethylglutaryl-CoA synthase and farnesyl diphosphate
      synthase, thereby inhibiting the endogenous production of cholesterol. The
      results from the present study provide important new knowledge for gaining
      insights into the molecular mechanisms of action of doxorubicin.

PMID- 20822188
TI  - Role of Hmbox1 in endothelial differentiation of bone-marrow stromal cells by a
      small molecule.
AB  - Bone marrow stromal cells (BMSCs) play critical roles in repairing endothelium
      damage. However, the mechanisms underlying BMSC differentiation into vascular
      endothelial cells (VECs) is not well understood. We aimed to find new factors
      involved in this process by exploiting a novel chemical inducer in a gene
      microarray assay. We first identified a novel benzoxazine derivative (6-amino-2,3
      dihydro-3-hydroxymethyl-1,4-benzoxazine; ABO) that can induce BMSC
      differentiation to VECs in a capillary-like tube formation assay, promote
      analysis of endothelial cell-specific marker expression, and facilitate uptake of
      1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-acetylated low
      density lipoprotein (Dil-Ac-LDL). Microarray analysis of BMSCs treated with ABO
      for 4 h revealed changes in only a handful of genes. The only one upregulated was
      homeobox-containing 1 (Hmbox1) gene, whereas six genes, including IP-10 and
      others, were downregulated. The upregulation of Hmbox1 and downregulation of IP
      10 were confirmed by RT-PCR, quantitative PCR (qPCR), and Western blot analysis.
      It is reported that IP-10 could suppresse EC differentiation into capillary
      structures. In this study ABO could not induce BMSC differentiation to VECs in
      the presence of IP-10. Small interfering RNA knockdown of Hmbox1 blocked ABO
      induced BMSC differentiation and increased the level of IP-10 but decreased Ets
      1. Thus, ABO is a novel inducer for BMSC differentiation to VECs, and Hmbox1 is a
      key factor in the differentiation. IP-10 and Ets-1 might be relevant targets of
      Hmbox1 in BMSC differentiation to VECs. These findings provide information on a
      novel target and a new platform for further investigating the gene control of
      BMSC differentiation to VECs.

PMID- 20822189
TI  - The efficacy of a targeted personalized drinking feedback intervention among
      intercollegiate athletes: a randomized controlled trial.
AB  - College athletes are an at-risk population for excessive alcohol use and
      subsequent alcohol-related harms. The purpose of this study was to test the
      efficacy of an electronically delivered personalized drinking feedback (PDF)
      intervention targeted specifically to college athletes, both in comparison with a
      standard (i.e., nontargeted) PDF intervention and an education-only (EO)
      condition that also included targeted information. Data were collected on 263
      intercollegiate athletes from three colleges (76% women, 86% White) who were
      randomly assigned to one of the conditions. Results provided partial support for
      the efficacy of the targeted PDF intervention. Students in the targeted PDF
      condition reported a lower peak blood alcohol concentration (BAC) at the 6-month
      follow-up than those in the other conditions. Heavy drinking students in the
      targeted PDF condition reported a lower peak BAC than those in the other
      conditions at the 1-month follow-up and a lower peak BAC than those in the EO
      condition at the 6-month follow-up. Finally, in-season athletes in the targeted
      PDF condition reported fewer drinks per week than those in the PDF-standard
      condition at the 1-month follow-up. These findings provide preliminary support
      for the use of targeted PDF interventions with at-risk alcohol users, such as
      college athletes.

PMID- 20822190
TI  - A risk model for disordered eating in late elementary school boys.
AB  - The authors tested the following risk model for disordered eating in late
      elementary school-age boys: Pubertal status is associated with increases in
      negative urgency, that is, the tendency to act rashly when distressed; high
      levels of negative urgency then influence binge eating through psychosocial
      learning; and binge eating influences purging. A sample of 908 fifth-grade boys
      completed questionnaire measures of puberty, negative urgency, dieting/thinness
      and eating expectancies, and eating pathology. Eating disorder symptoms were
      present in these young boys: 10% reported binge eating and 4.2% reported purging
      through self-induced vomiting. Each hypothesis in the risk model was supported.
      Boys this young do in fact engage in the maladaptive behaviors of binge eating
      and purging; it is crucial to develop explanatory risk models for this group. To
      this end, it appears that characteristics of boys, including their pubertal
      status, personalities, and psychosocial learning, help identify boys at risk.

PMID- 20822191
TI  - Subtyping pathological gamblers based on impulsivity, depression, and anxiety.
AB  - This study examined putative subtypes of pathological gamblers (PGs) based on the
      Pathways model, and it also evaluated whether the subtypes would benefit
      differentially from treatment. Treatment-seeking PGs (N = 229) were categorized
      into Pathways subtypes based on scores from questionnaires assessing anxiety,
      depression, and impulsivity. The Addiction Severity Index-Gambling assessed
      severity of gambling problems at baseline, posttreatment, and 12-month follow-up.
      Compared with behaviorally conditioned (BC) gamblers, emotionally vulnerable (EV)
      gamblers had higher psychiatric and gambling severity, and were more likely to
      have a parent with a psychiatric history. Antisocial impulsive (AI) gamblers also
      had elevated gambling and psychiatric severity relative to BC gamblers. They were
      more likely to have antisocial personality disorder and had the highest legal and
      family/social severity scores. They were also most likely to have a history of
      substance abuse treatment, history of inpatient psychiatric treatment, and a
      parent with a substance use or gambling problem. AI and EV gamblers experienced
      greater gambling severity throughout treatment than BC gamblers, but all three
      subtypes demonstrated similar patterns of treatment response. Thus, the three
      Pathways subtypes differ on some baseline characteristics, but subtyping did not
      predict treatment outcomes beyond a simple association with problem gambling
      severity.

PMID- 20822192
TI  - Risk factors for elementary school drinking: pubertal status, personality, and
      alcohol expectancies concurrently predict fifth grade alcohol consumption.
AB  - Little is known about the correlates and potential causes of very early drinking.
      The authors proposed this risk theory: (a) pubertal onset is associated with
      increased levels of positive urgency (the tendency to act rashly when
      experiencing intensely positive mood), negative urgency (the tendency to act
      rashly when distressed), and sensation seeking; (b) those traits predict
      increased endorsement of high-risk alcohol expectancies; (c) the expectancies
      predict drinker status among fifth graders; and (d) the apparent influence of
      positive urgency, negative urgency, and sensation seeking on drinker status is
      mediated by alcohol expectancies. The authors conducted a concurrent test of
      whether the relationships among these variables were consistent with the theory
      in a sample of 1,843 fifth grade students. In a well-fitting structural model,
      their hypotheses were supported. Drinker status among fifth graders is not just a
      function of context and factors external to children: it is predictable from a
      combination of pubertal status, personality characteristics, and learned alcohol
      expectancies.

PMID- 20822193
TI  - Do expectancies for reinforcement from smoking change after smoking initiation?
AB  - Expectancies are important predictors of smoking behavior. Recent research
      suggests that expectancies are not stable and vary across internal and external
      states and levels of cigarette consumption. Expectancies may also vary between
      individuals as a function of temperamental characteristics such as behavioral
      undercontrol (BU). Although pre-initiation expectancies have been linked to
      subsequent smoking behaviors, no study has assessed the effect of smoking
      initiation on expectancies. The present study was designed to test the hypotheses
      that both positive (PRE) and negative (NRE) reinforcement expectancies would
      increase following initiation, and that these changes would be moderated by BU.
      College students were interviewed 12-15 months apart. Those who initiated smoking
      between assessments (n = 69) were included in the present study. Linear mixed
      models showed a significant increase in PRE but not NRE from pre- to
      postinitiation. The relationship between NRE and time was moderated by BU, such
      that higher BU was associated with significantly larger post-initiation increases
      in NRE. Findings suggest that PRE and NRE change significantly following
      experience with smoking. Furthermore, undercontrolled, impulsive individuals may
      be particularly vulnerable to smoking with the intention of alleviating aversive
      states.

PMID- 20822194
TI  - Motivational pathways to unique types of alcohol consequences.
AB  - Individuals consume alcohol for a variety of reasons (motives), and these reasons
      may be differentially associated with the types of drinking outcomes that result.
      The present study examined whether specific affect-relevant motivations for
      alcohol use (i.e., coping, enhancement) are associated with distinct types of
      consequences, and whether such associations occur directly, or only as a function
      of increased alcohol use. It was hypothesized that enhancement motives would be
      associated with distinct problem types only through alcohol use, whereas coping
      motives would be linked directly to hypothesized problem types. Regularly
      drinking undergraduates (N = 192, 93 female) completed self-report measures of
      drinking motives and alcohol involvement. Using structural equation modeling, we
      tested direct associations between coping motives and indirect associations
      between enhancement motives and eight unique alcohol problem domains: risky
      behaviors, blackout drinking, physiological dependence, academic/occupational
      problems, poor self-care, diminished self-perception, social/interpersonal
      problems, and impaired control. We observed direct effects of coping motives on
      three unique problem domains (academic/occupational problems, risky behaviors,
      and poor self-care). Both coping and enhancement motives were indirectly
      associated (through use) with several problem types. Unhypothesized associations
      between conformity motives and unique consequence types also were observed.
      Findings suggest specificity in the consequences experienced by individuals who
      drink to cope with negative affect versus to enhance positive affect, and may
      have intervention implications. Findings depict the coping motivated student as
      one who is struggling across multiple domains, regardless of levels of drinking.
      Such students may need to be prioritized for interventions.

PMID- 20822195
TI  - Does it matter where we live?: The urban psychology of character strengths.
AB  - Psychology has neglected the study of variation across cities. An urban
      psychology is needed that takes seriously such variation and focuses on strengths
      and assets contributing to the good life as much as on problems of urbanization.
      To illustrate the value of an urban psychology, we describe studies of character
      strengths among residents in the 50 largest U.S. cities (N = 47,369). Differences
      in character strengths were found to exist across cities, were robustly related
      to important city-level outcomes such as entrepreneurship and 2008 presidential
      election voting, and were associated in theoretically predicted ways with city
      level features. We propose a framework that distinguishes between strengths of
      the "head," which are intellectual and self-oriented, and strengths of the
      "heart," which are emotional and interpersonal. Cities whose residents had higher
      levels of head strengths were those rated as creative and innovative. Head
      strengths predicted the likelihood of a city voting for Barack Obama, whereas
      heart strengths predicted voting for John McCain. More than half of the world's
      population now resides in cities, and urban psychology deserves greater
      attention.

PMID- 20822196
TI  - Statewide differences in personality: toward a psychological geography of the
      United States.
AB  - There is overwhelming evidence from research in the regional sciences that the
      attitudes, values, and behaviors of Americans are geographically clustered.
      Psychologists, however, have historically had little to say about regional
      differences. This article aims to redress that neglect. In so doing, I provide
      evidence that there are statewide personality differences across the United
      States, offer potential explanations for those differences, and show that
      regional personality differences are linked to a variety of important social
      indicators. I also explain how a regional perspective can inform research in a
      variety of areas in psychology and suggest ways in which researchers can study
      regional differences in their own work. Ultimately, this work is intended to
      raise awareness in psychology about the value that a regional perspective can add
      to theory and research.

PMID- 20822197
TI  - Ethos of independence across regions in the United States: the production
      adoption model of cultural change.
AB  - Contemporary U.S. culture has a highly individualistic ethos. Nevertheless,
      exactly how this ethos was historically fostered remains unanalyzed. A new model
      of dynamic cultural change maintains that sparsely populated, novel environments
      that impose major threats to survival, such as the Western frontier in the United
      States during the 18th and 19th centuries, breed strong values of independence,
      which in turn guide the production of new practices that encourage self-promotion
      and focused, competitive work. Faced with few significant threats to survival,
      residents in traditional areas are likely to seek social prestige by adopting
      existing practices of other, higher status groups. Because of both the massive
      economic success of the frontier and the official endorsement of the frontier by
      the federal government, eastern residents of the United States in the 18th and
      19th centuries may have actively adopted the frontier practices of independence,
      thus incorporating the frontier ethos of independence to form the contemporary
      U.S. national culture. Available evidence is reviewed, and implications for
      further research on cultural change are suggested.

PMID- 20822198
TI  - Children's contact with their incarcerated parents: research findings and
      recommendations.
AB  - Approximately 1.7 million children have parents who are incarcerated in prison in
      the United States, and possibly millions of additional children have a parent
      incarcerated in jail. Many affected children experience increased risk for
      developing behavior problems, academic failure, and substance abuse. For a
      growing number of children, incarcerated parents, caregivers, and professionals,
      parent-child contact during the imprisonment period is a key issue. In this
      article, we present a conceptual model to provide a framework within which to
      interpret findings about parent-child contact when parents are incarcerated. We
      then summarize recent research examining parent-child contact in context. On the
      basis of the research reviewed, we present initial recommendations for children's
      contact with incarcerated parents and also suggest areas for future intervention
      and research with this vulnerable population.

PMID- 20822199
TI  - The impact of deployment on U.S. military families.
AB  - Several recent articles have explored the effects of military deployment on U.S.
      service members' mental health outcomes. Although increased attention has also
      begun to focus on the effects of deployment on military families, providing a
      conceptualization for the mechanisms of this process can help organize existing
      information and inform future efforts. In this article we seek to draw greater
      attention to the effects of deployment on service members and to provide an
      overview of recent literature on the impact of deployment on service members and
      military families. A further goal is then to provide one conceptual perspective-
      a model of family stability--that may help inform our understanding of the impact
      of military deployment on families. Beyond informing research, the issues
      presented in this article have far-reaching consequences not only for American
      military families and their current mental health and primary care providers but
      also for practitioners in the broader mental health community who will be
      increasingly called upon to provide services to this population.

PMID- 20822206
TI  - Predicting adult occupational environments from gender and childhood personality
      traits.
AB  - To test aspects of a theory of the role of personality and gender on the
      development of vocational interests and their subsequent effects on adult
      occupational choices, the authors of this study examined associations among
      childhood personality traits, gender, and occupational environments more than 40
      years later. Participants (N = 587) were assessed on the Big Five by their
      teachers when the participants were between 6 and 12 years old. In middle-age
      (late 40s), the participants reported their occupation. Holland's (1997) RIASEC
      vocational types (Realistic, Investigative, Artistic, Social, Enterprising,
      Conventional) were used to characterize the job environments of reported
      occupations. Childhood Openness/Intellect and Conscientiousness, but no other Big
      Five traits, were associated with occupational environments. For the most
      strongly sex-typed work environments, associations with Openness/Intellect were
      moderated by gender. These findings suggest that the roots of the strongest
      gender-stereotyping effects in occupations may be found not only in the social
      factors associated with gender but also in the individual differences of children
      related to Openness/Intellect.

PMID- 20822207
TI  - Equality versus differentiation: the effects of power dispersion on group
      interaction.
AB  - Power is an inherent characteristic of social interaction, yet research has yet
      to fully explain what power and power dispersion may mean for conflict resolution
      in work groups. We found in a field study of 42 organizational work groups and a
      laboratory study of 40 negotiating dyads that the effects of power dispersion on
      conflict resolution are contingent on the level of interactants' power, thereby
      explaining contradictory theory and findings on power dispersion. We found that
      when members have low power, power dispersion is positively related to conflict
      resolution, but when members have high power, power dispersion is negatively
      related to conflict resolution (i.e., power equality is better). These findings
      can be explained by the mediating role of intragroup power struggles. Together,
      these findings suggest that power hierarchies function as a heuristic solution
      for conflict and contribute to adaptive social dynamics in groups with low, but
      not high, levels of power.

PMID- 20822208
TI  - A metaphor-enriched social cognition.
AB  - Social cognition is the scientific study of the cognitive events underlying
      social thought and attitudes. Currently, the field's prevailing theoretical
      perspectives are the traditional schema view and embodied cognition theories.
      Despite important differences, these perspectives share the seemingly
      uncontroversial notion that people interpret and evaluate a given social stimulus
      using knowledge about similar stimuli. However, research in cognitive linguistics
      (e.g., Lakoff & Johnson, 1980) suggests that people construe the world in large
      part through conceptual metaphors, which enable them to understand abstract
      concepts using knowledge of superficially dissimilar, typically more concrete
      concepts. Drawing on these perspectives, we propose that social cognition can and
      should be enriched by an explicit recognition that conceptual metaphor is a
      unique cognitive mechanism that shapes social thought and attitudes. To advance
      this metaphor-enriched perspective, we introduce the metaphoric transfer strategy
      as a means of empirically assessing whether metaphors influence social
      information processing in ways that are distinct from the operation of schemas
      alone. We then distinguish conceptual metaphor from embodied simulation--the
      mechanism posited by embodied cognition theories--and introduce the alternate
      source strategy as a means of empirically teasing apart these mechanisms.
      Throughout, we buttress our claims with empirical evidence of the influence of
      metaphors on a wide range of social psychological phenomena. We outline
      directions for future research on the strength and direction of metaphor use in
      social information processing. Finally, we mention specific benefits of a
      metaphor-enriched perspective for integrating and generating social cognitive
      research and for bridging social cognition with neighboring fields.

PMID- 20822209
TI  - Goal-directed aiming: two components but multiple processes.
AB  - This article reviews the behavioral literature on the control of goal-directed
      aiming and presents a multiple-process model of limb control. The model builds on
      recent variants of Woodworth's (1899) two-component model of speed-accuracy
      relations in voluntary movement and incorporates ideas about dynamic online limb
      control based on prior expectations about the efferent and afferent consequences
      of a planned movement. The model considers the relationship between movement
      speed and accuracy, and how performers adjust their trial-to-trial aiming
      behavior to find a safe, but fast, zone for movement execution. The model also
      outlines how the energy and safety costs associated with different movement
      outcomes contribute to movement planning processes and the control of aiming
      trajectories. Our theoretical position highlights the importance of advance
      knowledge about the sensory information that will be available for online control
      and the need to develop a robust internal representation of expected sensory
      consequences. We outline how early practice contributes to optimizing strategic
      planning to avoid worst-case outcomes associated with inherent neural-motor
      variability. Our model considers the role of both motor development and motor
      learning in refining feed-forward and online control. The model reconciles
      procedural and representational accounts of the specificity-of-learning
      phenomenon. Finally, we examine the breakdown of perceptual-motor precision in
      several special populations (i.e., Down syndrome, Williams syndrome, autism
      spectrum disorder, normal aging) within the framework of a multiple-process
      approach to goal-directed aiming.

PMID- 20822210
TI  - A review of contemporary ideomotor theory.
AB  - A framework for action planning, called ideomotor theory, suggests that actions
      are represented by their perceivable effects. Thus, any activation of the effect
      image, either endogenously or exogenously, will trigger the corresponding action.
      We review contemporary studies relating to ideomotor theory in which researchers
      have investigated various manipulations of action effects and how those effects
      acquire discriminative control over the actions. Evidence indicates that the
      knowledge about the relation between response and effect is still a critical
      component even when other factors, such as stimulus-response or response-response
      relations, are controlled. When consistent tone effects are provided after
      responses are made, performance in serial-reaction tasks is better than when the
      effects are random. Methodology in which acquisition and test stages are used
      with choice-reaction tasks shows that an action is automatically associated with
      its effect bilaterally and that anticipation of the effect facilitates action.
      Ideomotor phenomena include stimulus-response compatibility, in which the
      perceptual feature of the stimulus activates its corresponding action code when
      the stimulus itself resembles the effect codes. For this reason, other stimulus
      driven action facilitation such as ideomotor action and imitation are treated as
      ideomotor phenomena and are reviewed. Ideomotor theory also implies that ongoing
      action affects perception of concurrent events, a topic which we review briefly.
      Issues concerning ideomotor theory are identified and evaluated. We categorize
      the range of ideomotor explanations into several groups by whether intermediate
      steps are assumed to complete sensorimotor transformation or not and by whether a
      general theoretical framework or a more restricted one is provided by the
      account.

PMID- 20822211
TI  - Shifting perceptions: developmental changes in judgments of melodic similarity.
AB  - Musical melodies are recognized on the basis of pitch and temporal relations
      between consecutive tones. Although some previous evidence (e.g., Saffran &
      Griepentrog, 2001) points to an absolute-to-relative developmental shift in
      listeners' perception of pitch, other evidence (e.g., Plantinga & Trainor, 2005;
      Schellenberg & Trehub, 2003) suggests that both absolute- and relative-pitch
      processing are evident among listeners of all ages (infants, children, and
      adults). We attempted to resolve this apparent discrepancy by testing adults as
      well as children 5-12 years of age. On each trial, listeners rated how similar or
      how different 2 melodies sounded. The melodies were identical, transposed (all
      tones shifted in pitch by the same amount), different (same tones reordered,
      changing pitch relations between successive tones), or transposed and different.
      Listeners of all ages were sensitive to both changes, but younger listeners
      attended selectively to transpositions as a source of perceived differences. With
      increasing age, melodic differences played an increasingly important role,
      whereas transpositions became less relevant.

PMID- 20822212
TI  - The transmission and evolution of experimental microcultures in groups of young
      children.
AB  - A new experimental microculture approach was developed to investigate the
      creation and transmission of differing traditions in small communities of young
      children. Four playgroups, with a total of 88 children, participated. In each of
      2 playgroups, a single child was shown how to use 1 of 2 alternative methods of
      tool use, "lift" or "poke," to extract a reward from an artificial "foraging"
      device (the "panpipes") used in earlier diffusion experiments with chimpanzees.
      Each of these proficient models then participated in his or her playgroup during
      free play for 5 days, with the panpipes available to all. Compared with a
      condition in which no model was witnessed, where only 18% of children
      successfully gained rewards and the lift technique never appeared, 66% of
      children in the open diffusion conditions (83% of those who attempted the task)
      were successful. Each of the 2 different seeded approaches initially spread
      strongly in their respective groups. These seeded differences eroded over time as
      modifications were spontaneously invented, but social learning played a dominant
      role throughout, with a majority of children adopting the technique they
      witnessed most commonly, whether initially seeded or resulting from other
      children's innovations. A majority of children thus fell into 1 of several
      categories of "follower," relying primarily on social learning, with a minority
      displaying 1 of several other categories of innovation. One of the techniques was
      modified into a distinctively different form that was then socially transmitted
      further, allowing us to document the microevolution of small-scale traditions in
      this cultural microcosm.

PMID- 20822213
TI  - Do different types of school mathematics development depend on different
      constellations of numerical versus general cognitive abilities?
AB  - The purpose of this study was to examine the interplay between basic numerical
      cognition and domain-general abilities (such as working memory) in explaining
      school mathematics learning. First graders (N = 280; mean age = 5.77 years) were
      assessed on 2 types of basic numerical cognition, 8 domain-general abilities,
      procedural calculations, and word problems in fall and then reassessed on
      procedural calculations and word problems in spring. Development was indexed by
      latent change scores, and the interplay between numerical and domain-general
      abilities was analyzed by multiple regression. Results suggest that the
      development of different types of formal school mathematics depends on different
      constellations of numerical versus general cognitive abilities. When controlling
      for 8 domain-general abilities, both aspects of basic numerical cognition were
      uniquely predictive of procedural calculations and word problems development.
      Yet, for procedural calculations development, the additional amount of variance
      explained by the set of domain-general abilities was not significant, and only
      counting span was uniquely predictive. By contrast, for word problems
      development, the set of domain-general abilities did provide additional
      explanatory value, accounting for about the same amount of variance as the basic
      numerical cognition variables. Language, attentive behavior, nonverbal problem
      solving, and listening span were uniquely predictive.

PMID- 20822214
TI  - Gender-nonconforming lesbian, gay, bisexual, and transgender youth: school
      victimization and young adult psychosocial adjustment.
AB  - Past research documents that both adolescent gender nonconformity and the
      experience of school victimization are associated with high rates of negative
      psychosocial adjustment. Using data from the Family Acceptance Project's young
      adult survey, we examined associations among retrospective reports of adolescent
      gender nonconformity and adolescent school victimization due to perceived or
      actual lesbian, gay, bisexual, or transgender (LGBT) status, along with current
      reports of life satisfaction and depression. The participants included 245 LGBT
      young adults ranging in age from 21 to 25 years. Using structural equation
      modeling, we found that victimization due to perceived or actual LGBT status
      fully mediates the association between adolescent gender nonconformity and young
      adult psychosocial adjustment (i.e., life satisfaction and depression).
      Implications are addressed, including specific strategies that schools can
      implement to provide safer environments for gender-nonconforming LGBT students.

PMID- 20822215
TI  - The value of reanalysis and replication: introduction to special section.
AB  - In their 2007 article in this journal, Duncan et al. examined 6 longitudinal data
      sets to gauge the links between 3 key elements of readiness at school entry
      (academic, attention, and socioemotional skills) and later achievement. Across
      all 6 data sets, the strongest predictors of later achievement were school-entry
      math, reading, and attention skills. Social skills and internalizing and
      externalizing behavior did not predict subsequent achievement, even among
      children with relatively high levels of problem behavior. Patterns of association
      were similar for boys and girls and were not moderated by socioeconomic status.
      The 5 articles in this section reconsider the original findings and reanalyze the
      data involved. Overall, the thrust of these articles confirms the original
      article. The articles in this section, however, do offer some new insights. In
      general, the articles find somewhat more support for socioemotional factors,
      especially for prosocial skills, but the relationships involved are very small.
      Perhaps the most striking new finding is the added emphasis on fine motor skills,
      which is the focus of 2 articles. Taken together, the articles reveal the value
      of reanalysis and replication in developmental psychology.

PMID- 20822216
TI  - Early behavioral associations of achievement trajectories.
AB  - Duncan et al. (2007) examined associations between early behavioral and cognitive
      skills with later achievement. These associations were examined in 6 different
      data sets and results converged to suggest that early behavioral competences or
      problems had little, if any, prediction to later achievement and that attentional
      competences had small positive relations with later achievement. In contrast,
      cognitive abilities were by far the strongest predictors of achievement. We
      provide and investigate potential reasons why Duncan et al. found little to no
      association between behavior and later achievement in a reanalysis of data from 3
      studies previously analyzed by Duncan et al. Potential reasons include the
      validity of the behavioral measures, treatment of the behavioral measures as
      continuous as opposed to categorical, and the choice of data analytic method. In
      this article, we discuss these issues at greater length and address them in our
      reanalysis. We also bring into question the nature of the relationship between
      behavior and achievement. Generally, our reanalysis supports the idea that
      attention measures are more predictive than behavioral measures; however, certain
      behavior measures showed small to moderate associations to concurrent levels of
      academic achievement and changes in academic achievement through elementary
      school.

PMID- 20822217
TI  - School readiness and later achievement: a French Canadian replication and
      extension.
AB  - We first replicated the data analytic strategy used in Duncan et al. (2007) with
      a population-based data set of French-speaking children from Quebec (Canada).
      Prospective associations were examined between cognitive, attention, and
      socioemotional characteristics underlying kindergarten school readiness and
      second grade math, reading, and general achievement. We then extended this school
      readiness model by including motor skills as an additional element in the
      prediction equation and expanded the original strategy by including classroom
      engagement. The Montreal Longitudinal-Experimental Preschool Study, featured in
      Duncan et al., served as the Canadian reference group. In the replication model,
      kindergarten cognitive and attention characteristics predicted achievement by the
      end of 2nd grade. Although inconsistent across outcomes, behavioral problems and
      skills also emerged as predictors of some aspects of later achievement.
      Coefficients for kindergarten math skills were largest, followed by attention
      skills, receptive language skills, attention problems, and behavior. Most
      coefficients resembled those generated in the initial study. In our extension
      model, fine motor skills added their significant contribution to the prediction
      of later achievement above and beyond the original key elements of school
      readiness. Our extension model confirmed prospectively associations between
      kindergarten cognitive, attention, fine motor, and physical aggression
      characteristics and later achievement and classroom engagement by the end of 2nd
      grade. Although they comparatively showed better long-term benefits from stronger
      early attention skills, girls with less kindergarten cognitive skills were more
      vulnerable than boys with similar deficits when predicting 2nd grade math.

PMID- 20822218
TI  - School readiness and later achievement: replication and extension using a
      nationwide Canadian survey.
AB  - In this article we replicate and extend findings from Duncan et al. (2007). The
      1st study used Canada-wide data on 1,521 children from the National Longitudinal
      Survey of Children and Youth (NLSCY) to examine the influence of kindergarten
      literacy and math skills, mother-reported attention, and mother-reported
      socioemotional behaviors on 3rd-grade math and reading outcomes. Similar to
      Duncan et al., (a) math skills were the strongest predictor of later achievement,
      (b) literacy and attention skills predicted later achievement, and (c)
      socioemotional behaviors did not significantly predict later school achievement.
      As part of extending the findings, we incorporated a multiple imputation approach
      to handle missing predictor variable data. Results paralleled those from the
      original study in that kindergarten math skills and Peabody Picture Vocabulary
      Test-Revised scores continued to predict later achievement. However, we also
      found that kindergarten socioemotional behaviors, specifically
      hyperactivity/impulsivity, prosocial behavior, and anxiety/depression, were
      significant predictors of 3rd-grade math and reading. In the 2nd study, we used
      data from the NLSCY and the Montreal Longitudinal-Experimental Preschool Study
      (MLEPS), which was included in Duncan et al., to extend previous findings by
      examining the influence of kindergarten achievement, attention, and
      socioemotional behaviors on 3rd-grade socioemotional outcomes. Both NLSCY and
      MLEPS findings indicated that kindergarten math significantly predicted
      socioemotional behaviors. There were also a number of significant relationships
      between early and later socioemotional behaviors. Findings support the importance
      of socioemotional behaviors both as predictors of later school success and as
      indicators of school success.

PMID- 20822219
TI  - Fine motor skills and early comprehension of the world: two new school readiness
      indicators.
AB  - Duncan et al. (2007) presented a new methodology for identifying kindergarten
      readiness factors and quantifying their importance by determining which of
      children's developing skills measured around kindergarten entrance would predict
      later reading and math achievement. This article extends Duncan et al.'s work to
      identify kindergarten readiness factors with 6 longitudinal data sets. Their
      results identified kindergarten math and reading readiness and attention as the
      primary long-term predictors but found no effects from social skills or
      internalizing and externalizing behavior. We incorporated motor skills measures
      from 3 of the data sets and found that fine motor skills are an additional strong
      predictor of later achievement. Using one of the data sets, we also predicted
      later science scores and incorporated an additional early test of general
      knowledge of the social and physical world as a predictor. We found that the test
      of general knowledge was by far the strongest predictor of science and reading
      and also contributed significantly to predicting later math, making the content
      of this test another important kindergarten readiness indicator. Together,
      attention, fine motor skills, and general knowledge are much stronger overall
      predictors of later math, reading, and science scores than early math and reading
      scores alone.

PMID- 20822220
TI  - Longitudinal predictors of reading and math trajectories through middle school
      for African American versus Caucasian students across two samples.
AB  - This study's primary purpose was to examine the relative contribution of social
      behavioral predictors to reading and math skills. The study expands on Duncan et
      al.'s (2007) work by using longitudinal methodology from the National Institute
      of Child Health and Human Development's Study of Child Care and Youth Development
      (SECCYD) and the Early Childhood Longitudinal Study, Kindergarten Class of 1998
      1999 (ECLS-K) databases, and by focusing on potential differences in patterns of
      early predictors of later reading and math trajectories for African American
      versus Caucasian students. Predictor measures were selected at kindergarten, and
      the outcomes included standardized reading and math scores obtained from Grades
      1, 3, 5, and 9 for the SECCYD sample, and Grades 3, 5, and 8 for the ECLS-K
      sample. Consistent with Duncan et al.'s findings, results reflect the relative
      contributions of early reading and math skills to later functioning in these
      respective academic domains for both samples, and there are indications for the
      importance of early expressive language skills to both reading and math in the
      SECCYD sample. Findings related to the power of social-behavioral predictors,
      however, are not consistent across samples. Although the SECCYD sample evidenced
      no such predictors, several interactions in the ECLS-K sample suggested the
      moderating effects of early ratings of aggressive behaviors and internalizing
      behaviors on later reading and math for African American students. The moderating
      effects of early teacher ratings of attention and internalizing behaviors for
      African American students as compared with Caucasian students in later math
      growth also were noted. The importance of early social-behavioral functions as
      related to later academic skills remains an important area of inquiry.

PMID- 20822221
TI  - A tale of two methods: comparing regression and instrumental variables estimates
      of the effects of preschool child care type on the subsequent externalizing
      behavior of children in low-income families.
AB  - We apply instrumental variables (IV) techniques to a pooled data set of
      employment-focused experiments to examine the relation between type of preschool
      childcare and subsequent externalizing problem behavior for a large sample of low
      income children. To assess the potential usefulness of this approach for
      addressing biases that can confound causal inferences in child care research, we
      compare instrumental variables results with those obtained using ordinary least
      squares (OLS) regression. We find that our OLS estimates concur with prior
      studies showing small positive associations between center-based care and later
      externalizing behavior. By contrast, our IV estimates indicate that preschool
      aged children with center care experience are rated by mothers and teachers as
      having fewer externalizing problems on entering elementary school than their
      peers who were not in child care as preschoolers. Findings are discussed in
      relation to the literature on associations between different types of community
      based child care and children's social behavior, particularly within low-income
      populations. Moreover, we use this study to highlight the relative strengths and
      weaknesses of each analytic method for addressing causal questions in
      developmental research.

PMID- 20822222
TI  - Defining the boundary: age-related changes in childhood amnesia.
AB  - Childhood amnesia refers to the inability of adults to recall events that
      occurred during their infancy and early childhood. Although it is generally
      assumed that children and adolescents also experience childhood amnesia, with
      limited exceptions, most empirical research on the phenomenon has focused
      exclusively on adults. Here, we developed a new Timeline procedure to directly
      compare the early memories reported by children, adolescents, and adults.
      Overall, the proportion of memories reported before the age of 3 years was
      greater for the children and adolescents relative to the adults. In addition, the
      single earliest memory reported by children and adolescents was at a younger age
      than that reported by adults. In fact, the earliest memories reported by the
      children and adolescents, but not the adults, were significantly younger than the
      traditional 3 (1/2)-year-old boundary of childhood amnesia. Regardless of the age
      of the rememberer, participants' early memories had the same episodic
      characteristics. We conclude that the boundary and the density of childhood
      amnesia may increase over the course of human development and that age-related
      changes in basic memory mechanisms make an important contribution to our
      understanding of the source of childhood amnesia.

PMID- 20822223
TI  - Children's early approaches to learning and academic trajectories through fifth
      grade.
AB  - Children's early approaches to learning (ATL) enhance their adaptation to the
      demands they experience with the start of formal schooling. The current study
      uses individual growth modeling to investigate whether children's early ATL,
      which includes persistence, emotion regulation, and attentiveness, explain
      individual differences in their academic trajectories during elementary school.
      Using data from the Early Childhood Longitudinal Study - Kindergarten Cohort
      (ECLS-K), the present investigation examined the association between ATL at
      kindergarten entry and trajectories of reading and math achievement across 6
      waves of data from kindergarten, 1st, 3rd, and 5th grade (n = 10,666). The
      current study found a positive link between early ATL and individual trajectories
      of reading and math performance. Overall, children's early ATL was equally
      beneficial for children regardless of their race/ethnicity and dimensions of
      their socioeconomic background. However, links between early ATL and academic
      trajectories differed by their gender and initial levels of math and reading
      achievement.

PMID- 20822224
TI  - Traits as dimensions or categories? Developmental change in the understanding of
      trait terms.
AB  - Recent research has suggested that young children have relatively well-developed
      trait concepts. However, this literature overlooks potential age-related
      differences in children's appreciation of the fundamentally dimensional nature of
      traits. In Study 1, we presented 4-, 5-, and 7-year-old children and adults with
      sets of characters and asked them to indicate the preferences of a target
      character who shared appearance attributes with one character (appearance match)
      and shared a common trait with the other character (trait match). Traits were
      presented in a way that emphasized either their categorical or their dimensional
      nature. When the dimensional nature of trait terms was emphasized, the youngest
      children made fewer trait-based inferences, and the use of traits increased with
      age. In Study 2, we gave 4-year-old children and adults the same task except that
      the extent to which appearance cues could serve as a meaningful basis of judgment
      was varied. Results were consistent with the findings of Study 1, although
      children were more likely to rely on dimensional presentations of traits in the
      absence of strong appearance cues. (PsycINFO Database Record (c) 2010 APA, all
      rights reserved).

PMID- 20822225
TI  - Contributions of child's physiology and maternal behavior to children's
      trajectories of temperamental reactivity.
AB  - Trajectories of children's temperamental reactivity (negative affectivity and
      surgency) were examined in a community sample of 370 children across the ages of
      4 to 7 with hierarchical linear modeling. Children's physiological reactivity
      (respiratory sinus arrhythmia [RSA]), physiological regulation (Delta RSA), and
      maternal parenting behavior were included as predictors of children's
      trajectories of temperamental reactivity. Results indicated that negative
      affectivity and surgency decreased from 4 to 7 years of age; however, within
      person changes in negative affectivity were dependent on levels of baseline RSA
      and not age. Increases in negative affectivity were also predicted by higher
      levels of earlier maternal controlling behavior. Decreases in surgency were
      predicted by higher levels of Delta RSA during mother-child interaction tasks and
      positive parenting behavior. Baseline RSA and maternal controlling parenting also
      accounted for interindividual differences in children's negative affectivity at
      age 7, and gender and children's baseline RSA accounted for interindividual
      differences in children's surgency at age 7. Overall, these results provide
      further evidence that parenting behavior and children's RSA influence the changes
      that occur in children's temperamental reactivity.

PMID- 20822226
TI  - The nature and impact of changes in home learning environment on development of
      language and academic skills in preschool children.
AB  - In this study, we examined changes in the early home learning environment as
      children approached school entry and whether these changes predicted the
      development of children's language and academic skills. Findings from a national
      sample of the National Institute of Child Health and Human Development Study of
      Early Child Care and Youth Development (N = 1,018) revealed an overall
      improvement in the home learning environment from 36 to 54 months of children's
      age, with 30.6% of parents of preschoolers displaying significant improvement in
      the home environment (i.e., changes greater than 1 SD) and with only 0.6% showing
      a decrease. More important, the degree of change uniquely contributed to the
      children's language but not to their academic skills. Home changes were more
      likely to be observed from mothers with more education and work hours and with
      fewer symptoms of depression.

PMID- 20822227
TI  - With development, list recall includes more chunks, not just larger ones.
AB  - The nature of the childhood development of immediate recall has been difficult to
      determine. There could be a developmental increase in either the number of chunks
      held in working memory or the use of grouping to make the most of a constant
      capacity. In 3 experiments with children in the early elementary school years and
      adults, we show that improvements in the immediate recall of word and picture
      lists come partly from increases in the number of chunks of items retained in
      memory. This finding was based on a distinction between access to a studied group
      of items (i.e., recall of at least 1 item from the group) and completion of the
      accessed group (i.e., the proportion of the items recalled from the group).
      Access rates increased with age, even with statistical controls for completion
      rates, implicating development of capacity in chunks.

PMID- 20822228
TI  - Risk and resilience factors in coping with daily stress in adulthood: the role of
      age, self-concept incoherence, and personal control.
AB  - This study observed young, middle-aged, and older adults (N = 239; Mage = 49.6
      years; range = 18-89 years) for 30 consecutive days to examine the association
      between daily stress and negative affect, taking into account potential risk
      (i.e., self-concept incoherence) and resilience (i.e., age, perceived personal
      control) factors. Results indicated that younger individuals and individuals with
      a more incoherent self-concept showed higher average negative affect across the
      study. As well, individuals reported higher negative affect on days that they
      experienced more stress than usual and on days that they reported less control
      than usual. These main effects were qualified by significant interactions. In
      particular, the association between daily stress and negative affect was stronger
      on days on which adults reported low control compared with days on which they
      reported high control (i.e., perceptions of control buffered stress). Reactivity
      to daily stress did not differ for individuals of different ages or for
      individuals with different levels of self-concept incoherence. Although all
      individuals reported higher negative affect on days on which they reported less
      control than usual, this association was more pronounced among younger adults.
      The current study helps to elucidate the role of risk and resilience factors when
      adults are faced with daily stress.

PMID- 20822229
TI  - Genetic liability, environment, and the development of fussiness in toddlers: the
      roles of maternal depression and parental responsiveness.
AB  - Using a longitudinal, prospective adoption design, the authors of this study
      examined the effects of the environment (adoptive parents' depressive symptoms
      and responsiveness) and genetic liability of maternal depression (inferred by
      birth mothers' major depressive disorder [MDD]) on the development of fussiness
      in adopted children between 9 and 18 months old. The sample included 281 families
      linked through adoption, with each family including 4 individuals (i.e., adopted
      child, birth mother, adoptive father and mother). Results showed that adoptive
      mothers' depressive symptoms when their child was 9 months old were positively
      associated with child fussiness at 18 months. A significant interaction between
      birth mothers' MDD and adoptive mothers' responsiveness indicated that children
      of birth mothers with MDD showed higher levels of fussiness at 18 months when
      adoptive mothers had been less responsive to the children at 9 months. However,
      in the context of high levels of adoptive mothers' responsiveness, children of
      birth mothers with MDD did not show elevated fussiness at 18 months. Findings are
      discussed in terms of gene-environment interactions in the intergenerational risk
      transmission of depression.

PMID- 20822230
TI  - Trajectories of pure and co-occurring internalizing and externalizing problems
      from age 2 to age 12: findings from the National Institute of Child Health and
      Human Development Study of Early Child Care.
AB  - How and why do internalizing and externalizing problems, psychopathological
      problems from different diagnostic classes representing separate forms of
      psychopathology, co-occur in children? We investigated the development of pure
      and co-occurring internalizing and externalizing problems from ages 2 to 12 with
      the use of latent class growth analysis. Furthermore, we examined how early
      childhood factors (temperament, cognitive functioning, maternal depression, and
      home environment) and early adolescent social and behavioral adjustment variables
      were related to differential trajectories of pure and co-occurring internalizing
      and externalizing problems. The sample (National Institute of Child Health and
      Human Development Study of Early Child Care) consisted of 1,232 children (52%
      male). Mother reports on the Child Behavior Checklist (Achenbach, 1991, 1992)
      were used to construct the trajectories of externalizing and internalizing
      problems. Analyses identified groups of children exhibiting pure and co-occurring
      internalizing and externalizing problems. Children exhibiting continuous
      externalizing or continuous co-occurring internalizing and externalizing problems
      across the 10-year period under investigation were more likely to (a) engage in
      risky behaviors, (b) be associated with deviant peers, (c) be rejected by peers,
      and (d) be asocial with peers at early adolescence. However, children exhibiting
      pure internalizing problems over time were only at higher risk for being asocial
      with peers as early adolescents. Moreover, the additive effects of individual and
      environmental early childhood risk factors influenced the development of chronic
      externalizing problems, although pure internalizing problems were uniquely
      influenced by maternal depression. Results also provided evidence for the
      concepts of equifinality and multifinality.

PMID- 20822231
TI  - Preschool executive functioning abilities predict early mathematics achievement.
AB  - Impairments in executive function have been documented in school-age children
      with mathematical learning difficulties. However, the utility and specificity of
      preschool executive function abilities in predicting later mathematical
      achievement are poorly understood. This study examined linkages between
      children's developing executive function abilities at age 4 and children's
      subsequent achievement in mathematics at age 6, 1 year after school entry. The
      study sample consisted of a regionally representative cohort of 104 children
      followed prospectively from ages 2 to 6 years. At age 4, children completed a
      battery of executive function tasks that assessed planning, set shifting, and
      inhibitory control. Teachers completed the preschool version of the Behavior
      Rating Inventory of Executive Function. Clinical and classroom measures of
      children's mathematical achievement were collected at age 6. Results showed that
      children's performance on set shifting, inhibitory control, and general executive
      behavior measures during the preschool period accounted for substantial
      variability in children's early mathematical achievement at school. These
      associations persisted even after individual differences in general cognitive
      ability and reading achievement were taken into account. Findings suggest that
      early measures of executive function may be useful in identifying children who
      may experience difficulties learning mathematical skills and concepts. They also
      suggest that the scaffolding of these executive skills could potentially be a
      useful additional component in early mathematics education.

PMID- 20822233
TI  - Attributions of intentions and fairness judgments regarding interracial peer
      encounters.
AB  - To investigate how adolescents interpret ambiguous actions in hypothetical
      interracial peer encounters, we conducted a study in which 8th- and 11th-grade
      students (N = 837) evaluated 4 interracial peer encounters in which the
      intentions of the protagonist were ambiguous. The sample was evenly divided by
      gender and included both African American and European American adolescents.
      European American students, male adolescents, and 8th graders were more likely to
      attribute negative intentions to the protagonist in interracial exchanges than
      were African American students, female adolescents, and 11th graders. Although
      all participants viewed peer and teacher accusations of wrongdoing in ambiguous
      situations as unfair, ethnic minority students as well as female adolescents
      rated accusations of wrongdoing as more unfair than did ethnic majority or male
      adolescents. Eleventh graders were more likely to view accusations of wrongdoing
      for protagonists with a prior history of transgression as fair than were 8th
      graders. The findings are discussed in light of efforts to reduce prejudice and
      to facilitate positive intergroup peer interactions.

PMID- 20822232
TI  - Early temperamental and family predictors of shyness and anxiety.
AB  - With a sample of 242 twins (135 girls, 107 boys) studied longitudinally,
      behavioral inhibition (BI) and inhibitory control (IC) measured at 3 years, as
      well as early and concurrent family process variables, were examined as
      predictors of shyness and of anxiety symptoms approximately 4 years later.
      Structured observational data from laboratory and home contexts were used in
      conjunction with parent and experimenter ratings. A key goal was to extend
      previous findings of the positive relationship between early BI and anxiety
      development by incorporating the consideration of IC and family process
      variables. Using hierarchical linear modeling with restricted maximum likelihood
      estimation to adjust for twin dependency, early BI (b = 0.37, p < .01), IC (b =
      0.14, p < .05), and concurrent lower family stress (b = -0.22, p < .05) predicted
      shyness during middle childhood. Findings were similar for parent-rated and
      laboratory-based shyness measures. Anxiety symptoms were predicted by BI (b =
      0.14, p < .05), early negative family affect (b = 0.20, p < .05), and family
      stress in middle childhood (b = 0.26, p < .05). These findings clarify the
      relative importance of temperament and family factors in the development of both
      shyness and anxiety symptoms during childhood.

PMID- 20822234
TI  - Parental socialization of sadness regulation in middle childhood: the role of
      expectations and gender.
AB  - The authors of this study investigated mothers' and fathers' socialization of
      their children's sadness. The particular focus was an examination of how
      socialization practices changed when parents' expectancies concerning their
      child's sadness management abilities were violated. Methods included an
      experimental manipulation and direct observation of parent-child interactions in
      62 families of White, middle-class children in 3rd and 4th grades. Families were
      randomly assigned to 1 of 2 conditions. After parents were provided with a
      description of normative child behavior on a sadness-induction task, feedback was
      manipulated such that parents in the control condition were told their child had
      demonstrated typical regulation while parents in the violated-expectancy
      condition were informed their child did not manage sadness as well as peers. The
      hypothesis that violated expectancies influence socialization processes was
      supported, with greater evidence emerging for fathers than mothers. In certain
      circumstances within the violated-expectancy condition, there was more parental
      similarity in socialization practices than in the control condition. Further,
      mother-father comparisons indicated differences in socialization as a function of
      parent and child gender that were generally consistent with gender stereotypes.

PMID- 20822236
TI  - Parental work schedules and adolescent risky behaviors.
AB  - Using a large contemporary data set (the National Longitudinal Survey of Youth
      Child Supplement), the authors examined the effects of parental work schedules on
      adolescent risky behaviors at age 13 or 14 and the mechanisms that might explain
      them. Structural equation modeling suggests mothers who worked more often at
      night spent significantly less time with children and had lower quality home
      environments, and these mediators were significantly linked to adolescent risky
      behaviors. Similar effects were not found for evening work schedules, while other
      types of maternal and paternal nonstandard work schedules were linked to higher
      parental knowledge of children's whereabouts, which led to lower levels of
      adolescent risky behaviors. Subgroup analyses revealed that boys, those in
      families with low incomes, and those whose mothers never worked at professional
      jobs may particularly be affected by mothers working at nights, due to spending
      less time together, having a lower degree of maternal closeness, and experiencing
      lower quality home environments. In addition, the effects of maternal night
      shifts were particularly pronounced if children were in the preschool or middle
      childhood years when their mothers worked those schedules. Implications and
      avenues for future research are discussed.

PMID- 20822235
TI  - Understanding the positive role of neighborhood socioeconomic advantage in
      achievement: the contribution of the home, child care, and school environments.
AB  - The goal of this study was to examine the mechanisms underlying associations
      between neighborhood socioeconomic advantage and children's achievement
      trajectories between ages 54 months and 15 years. Results of hierarchical linear
      growth models based on a diverse sample of 1,364 children indicate that
      neighborhood socioeconomic advantage was nonlinearly associated with youths'
      initial vocabulary and reading scores, such that the presence of educated,
      affluent professionals in the neighborhood had a favorable association with
      children's achievement among those in less advantaged neighborhoods until it
      leveled off at moderate levels of advantage. A similar tendency was observed for
      math achievement. The quality of the home and child care environments as well as
      school advantage partially explained these associations. The findings suggest
      that multiple environments need to be considered simultaneously for understanding
      neighborhood-achievement links.

PMID- 20822237
TI  - A multiprocess account of hindsight bias in children.
AB  - In hindsight, that is, after receiving the correct answers to difficult
      questions, people's recall of their own prior answers tends to be biased toward
      the correct answers. We tested 139 participants from 3 age groups (9- and 12-year
      olds and adults) in a hindsight-bias paradigm and found that all groups showed
      hindsight bias. Multinomial model-based analyses indicated that all age groups
      used the correct answers to reconstruct their original answers. In addition, the
      youngest group showed memory impairment caused by the presentation of the correct
      answers as well as an increased belief that they knew the correct answers all
      along. These results support a multiprocess explanation of hindsight bias in
      children.

PMID- 20822238
TI  - Video comprehensibility and attention in very young children.
AB  - Earlier research established that preschool children pay less attention to
      television that is sequentially or linguistically incomprehensible. The authors
      of this study determined the youngest age for which this effect can be found. One
      hundred and three 6-, 12-, 18-, and 24-month-olds' looking and heart rate were
      recorded while they watched Teletubbies, a television program designed for very
      young children. Experimenters manipulated comprehensibility by either randomly
      ordering shots or reversing dialogue to become backward speech. Infants watched 1
      normal segment and 1 distorted version of the same segment. Only 24-month-olds,
      and to some extent 18-month-olds, distinguished between normal and distorted
      videos by looking for longer durations toward the normal stimuli. The results
      suggest that it may not be until the middle of the second year that children
      demonstrate the earliest beginnings of comprehension of video as it is currently
      produced.

PMID- 20822239
TI  - Mothers' teaching strategies and children's effortful control: a longitudinal
      study.
AB  - Findings on the relation of maternal verbal teaching strategies to children's
      effortful control (EC; i.e., self-regulation) are limited in quantity and
      somewhat inconsistent. In this study, children's EC was assessed at 18, 30, and
      42 months (ns = 255, 229, and 209, respectively) with adults' reports and a
      behavioral measure. Mothers' verbal teaching strategies were assessed while the
      mother and child worked on a task together. Children's general vocabulary also
      was measured. In a structural panel model taking into account prior levels of
      constructs and correlations within time, as well as the relations of EC and
      teaching strategies to children's vocabulary, socioeconomic status, age, and sex
      of the child, 18-month EC positively predicted mothers' 30-month cognitive
      assistance and questioning strategies and negatively predicted 30-month maternal
      directive strategies. In addition, high 30-month EC predicted greater 42-month
      maternal cognitive assistance and fewer directive strategies. Thus, mothers'
      teaching strategies were predicted by individual differences in self-regulatory
      skills, supporting potential evocative child effects on mothers' teaching
      strategies.

PMID- 20822240
TI  - What counts in the development of young children's number knowledge?
AB  - Prior studies indicate that children vary widely in their mathematical knowledge
      by the time they enter preschool and that this variation predicts levels of
      achievement in elementary school. In a longitudinal study of a diverse sample of
      44 preschool children, we examined the extent to which their understanding of the
      cardinal meanings of the number words (e.g., knowing that the word "four" refers
      to sets with 4 items) is predicted by the "number talk" they hear from their
      primary caregiver in the early home environment. Results from 5 visits showed
      substantial variation in parents' number talk to children between the ages of 14
      and 30 months. Moreover, this variation predicted children's knowledge of the
      cardinal meanings of number words at 46 months, even when socioeconomic status
      and other measures of parent and child talk were controlled. These findings
      suggest that encouraging parents to talk about number with their toddlers, and
      providing them with effective ways to do so, may positively impact children's
      school achievement.

PMID- 20822241
TI  - Children's conscience during toddler and preschool years, moral self, and a
      competent, adaptive developmental trajectory.
AB  - We investigated whether children's robust conscience, formed during early family
      socialization, promotes their future adaptive and competent functioning in
      expanded ecologies. We assessed two dimensions of conscience in young children (N
      = 100) at 25, 38, and 52 months in scripted laboratory contexts: internalization
      of their mothers' and fathers' rules, observed when the child was alone, and
      empathic concern toward each parent, observed in simulated distress paradigms. We
      also assessed the child's self-perception on moral dimensions (the moral self),
      using a puppet interview at 67 months. At 80 months, parents and teachers
      produced an overall measure of competent, adaptive functioning by rating children
      on multiple scales of competent, prosocial, rule-abiding behavior and antisocial
      behavior. As expected, children with histories of a stronger internalization of
      both parents' rules were more competent and better socialized; for maternal
      rules, that link was mediated by the child's moral self. The link between the
      child's history of empathy toward the mother and future socialization was also
      significant, but it was not mediated by the moral self. This study elucidates the
      roles of classic components of morality--moral conduct, affect, and self--as
      antecedents of an adaptive developmental trajectory from toddler to early school
      age.

PMID- 20822242
TI  - The impact of generic language about ability on children's achievement
      motivation.
AB  - Nuances in how adults talk about ability may have important consequences for
      children's sustained involvement and success in an activity. In this study, I
      tested the hypothesis that children would be less motivated while performing a
      novel activity if they were told that boys or girls in general are good at this
      activity (generic language) than if they were told that a particular boy or girl
      is good at it (non-generic language). Generic language may be detrimental because
      it expresses normative societal expectations regarding performance. If these
      expectations are negative, they may cause children to worry about confirming
      them; if positive, they may cause worries about failing to meet them. Moreover,
      generic statements may be threatening because they imply that performance is the
      result of stable traits rather than effort. Ninety-seven 4- to 7-year-olds were
      asked to play a game in which they succeeded at first but then made a few
      mistakes. Since young children remain optimistic in achievement situations until
      the possibility of failure is made clear, I hypothesized that 4- and 5-year-olds
      would not be affected by the implications of generic language until after they
      made mistakes; 6- and 7-year-olds, however, may be susceptible earlier. As
      expected, the older children who heard that boys or girls are good at this game
      displayed lower motivation (e.g., more negative emotions, lower perceived
      competence) from the start, while they were still succeeding and receiving
      praise. Four- and 5-year-olds who heard these generic statements had a similar
      reaction, but only after they made mistakes. These findings demonstrate that
      exposure to generic language about ability can be an obstacle to children's
      motivation and, potentially, their success.

PMID- 20822243
TI  - Development's tortoise and hare: pubertal timing, pubertal tempo, and depressive
      symptoms in boys and girls.
AB  - Although the sequence of pubertal maturation remains consistent across most
      individuals, the timing and tempo of development fluctuate widely. While past
      research has largely focused on the sequelae of pubertal timing, a faster tempo
      of maturation might also present special challenges to children for acclimating
      to new biological and social milestones. Using latent growth curve modeling, the
      present study investigated how pubertal tempo and pubertal timing predicted
      depressive symptoms over a 4-year period in a sample of children recruited from
      New York City area public schools. Rate of intraindividual change in parent
      reported Tanner stages was used as an index of pubertal tempo, and more advanced
      Tanner development at an earlier chronological age was used as an index of
      pubertal timing. For girls (N = 138, M = 8.86 years old at Time 1), pubertal
      timing emerged as the most salient factor, and the tempo at which girls
      progressed through puberty was not significant. In boys (N = 128, M = 9.61 years
      old at Time 1), both timing and tempo of development were significant; notably,
      however, the effects of pubertal tempo were stronger than those of timing. These
      findings highlight the need to consider multiple sources of individual
      variability in pubertal development and suggest different pubertal challenges for
      boys and girls.

PMID- 20822244
TI  - Ability mindsets influence the quality of mothers' involvement in children's
      learning: an experimental investigation.
AB  - This research examined the role of mothers' mindsets about the malleability of
      children's ability in the quality of their involvement in children's learning.
      Mothers (N = 79) of early elementary school children (mean age = 7.65 years) were
      induced to hold either an entity mindset, in which children's ability is seen as
      unchangeable, or an incremental mindset, in which children's ability is seen as
      changeable. Mothers and children were then observed as they worked on a set of
      challenging problems for 15 min. Unconstructive involvement (i.e., performance
      oriented teaching, control, and negative affect) was more frequent among mothers
      induced to hold an entity mindset than those induced to hold an incremental
      mindset. Mothers with an entity (vs. incremental) mindset also responded to
      children's helplessness more unconstructively.

PMID- 20822245
TI  - Developmental progression of looking and reaching performance on the A-not-B
      task.
AB  - From a neuropsychological perspective, the cognitive skills of working memory,
      inhibition, and attention and the maturation of the frontal lobe are requisites
      for successful A-not-B performance on both the looking and reaching versions of
      the task. This study used a longitudinal design to examine the developmental
      progression of infants' performance on the looking and reaching versions of the A
      not-B task. Twenty infants were tested on both versions of the task once a month
      from 5 to 10 months of age. Infants had higher object permanence scores on the
      looking version of the task from 5 to 8 months, with comparable performance
      across response modalities at 9 and 10 months. The same pattern of performance
      was found on nonreversal (A) trials: Infants performed better on looking trials
      from 5 to 7 months, and they performed equally on both response trials from 8 to
      10 months. Overall, infants performed better on looking reversal (B) trials than
      reaching reversal trials. These data suggest that performance differences between
      response modalities early in development can be attributed to major differences
      in the maturation of brain circuitry associated with the actual task response.

PMID- 20822246
TI  - An intersectional approach for understanding perceived discrimination and
      psychological well-being among African American and Caribbean Black youth.
AB  - The present study examined whether combinations of ethnicity, gender, and age
      moderated the association between perceived discrimination and psychological well
      being indicators (depressive symptoms, self-esteem, and life satisfaction) in a
      nationally representative sample of Black youth. The data were from the National
      Survey of American Life, which includes 810 African American and 360 Caribbean
      Black adolescents. The results indicated main effects such that perceived
      discrimination was linked to increased depressive symptoms and decreased self
      esteem and life satisfaction. Additionally, there were significant interactions
      for ethnicity, gender, and race. Specifically, older Caribbean Black female
      adolescents exhibited higher depressive symptoms and lower life satisfaction in
      the context of high levels of perceived discrimination compared with older
      African American male adolescents.

PMID- 20822247
TI  - Selective information seeking after a single encounter.
AB  - In 3 experiments, the authors examined whether a single act of testimony can
      inform children's subsequent information seeking. In Experiment 1, participants
      saw one informant give a correct and another informant give an incorrect answer
      to a question, assessed who was right (wrong), and decided to whom to address a
      2nd question. Adults and 7-year-olds but not 4-year-olds selected the previously
      correct informant. In Experiment 2, after assessing which informant was (not)
      very good at answering, even 4-year-olds selected the previously correct
      informant. In Experiment 3, in the absence of external demands to evaluate the
      informants, 7-year-olds and adults still selected the previously correct
      informant. Thus, a single encounter is sufficient for 7-year-olds and adults to
      engage in selective information seeking and trait labels enable 4-year-olds to do
      so too.

PMID- 20822248
TI  - Are you thinking what I'm thinking? Peer group similarities in adolescent hostile
      attribution tendencies.
AB  - A bias toward attributing hostile intent to others has been linked to aggression.
      In an adolescent sample, the question of whether peer group homophily exists in
      the tendency toward attributing hostile intent was investigated. Hostile
      attribution tendencies and self-reported aggressive behaviors were assessed in a
      normative sample of 910 adolescents and average peer group scores were computed
      on the basis of nominated friend scores. Results indicated that adolescents
      showed significant correlations between their own level of hostile attributions
      and that of their peer group. Further analyses indicated that this effect
      occurred specifically in reciprocal friendships and was retained even when own
      and peer group levels of aggression were controlled.

PMID- 20822249
TI  - A general multilevel SEM framework for assessing multilevel mediation.
AB  - Several methods for testing mediation hypotheses with 2-level nested data have
      been proposed by researchers using a multilevel modeling (MLM) paradigm. However,
      these MLM approaches do not accommodate mediation pathways with Level-2 outcomes
      and may produce conflated estimates of between- and within-level components of
      indirect effects. Moreover, these methods have each appeared in isolation, so a
      unified framework that integrates the existing methods, as well as new multilevel
      mediation models, is lacking. Here we show that a multilevel structural equation
      modeling (MSEM) paradigm can overcome these 2 limitations of mediation analysis
      with MLM. We present an integrative 2-level MSEM mathematical framework that
      subsumes new and existing multilevel mediation approaches as special cases. We
      use several applied examples and accompanying software code to illustrate the
      flexibility of this framework and to show that different substantive conclusions
      can be drawn using MSEM versus MLM.

PMID- 20822251
TI  - The importance of covariate selection in controlling for selection bias in
      observational studies.
AB  - The assumption of strongly ignorable treatment assignment is required for
      eliminating selection bias in observational studies. To meet this assumption,
      researchers often rely on a strategy of selecting covariates that they think will
      control for selection bias. Theory indicates that the most important covariates
      are those highly correlated with both the real selection process and the
      potential outcomes. However, when planning a study, it is rarely possible to
      identify such covariates with certainty. In this article, we report on an
      extensive reanalysis of a within-study comparison that contrasts a randomized
      experiment and a quasi-experiment. Various covariate sets were used to adjust for
      initial group differences in the quasi-experiment that was characterized by self
      selection into treatment. The adjusted effect sizes were then compared with the
      experimental ones to identify which individual covariates, and which conceptually
      grouped sets of covariates, were responsible for the high degree of bias
      reduction achieved in the adjusted quasi-experiment. Such results provide strong
      clues about preferred strategies for identifying the covariates most likely to
      reduce bias when planning a study and when the true selection process is not
      known.

PMID- 20822252
TI  - Testing multiple outcomes in repeated measures designs.
AB  - This study investigates procedures for controlling the familywise error rate
      (FWR) when testing hypotheses about multiple, correlated outcome variables in
      repeated measures (RM) designs. A content analysis of RM research articles
      published in 4 psychology journals revealed that 3 quarters of studies tested
      hypotheses about 2 or more outcome variables. Several procedures originally
      proposed for testing multiple outcomes in 2-group designs are extended to 2-group
      RM designs. The investigated procedures include 2 modified Bonferroni procedures
      that adjust the level of significance, alpha, for the effective number of
      outcomes and a permutation step-down (PSD) procedure. The FWR, any-variable
      power, and all-variable power are investigated in a Monte Carlo study. One
      modified Bonferroni procedure frequently resulted in inflated FWRs, whereas the
      PSD procedure controlled the FWR. The PSD procedure could be substantially more
      powerful than the conventional Bonferroni procedure, which does not account for
      dependencies among the outcome variables. However, the difference in power
      between the PSD procedure, which does account for these dependencies, and
      Hochberg's step-up procedure, which does not, were negligible. A numeric example
      illustrates implementation of these multiple-testing procedures.

PMID- 20822250
TI  - Propensity score techniques and the assessment of measured covariate balance to
      test causal associations in psychological research.
AB  - There is considerable interest in using propensity score (PS) statistical
      techniques to address questions of causal inference in psychological research.
      Many PS techniques exist, yet few guidelines are available to aid applied
      researchers in their understanding, use, and evaluation. In this study, the
      authors give an overview of available techniques for PS estimation and PS
      application. They also provide a way to help compare PS techniques, using the
      resulting measured covariate balance as the criterion for selecting between
      techniques. The empirical example for this study involves the potential causal
      relationship linking early-onset cannabis problems and subsequent negative mental
      health outcomes and uses data from a prospective cohort study. PS techniques are
      described and evaluated on the basis of their ability to balance the
      distributions of measured potentially confounding covariates for individuals with
      and without early-onset cannabis problems. This article identifies the PS
      techniques that yield good statistical balance of the chosen measured covariates
      within the context of this particular research question and cohort.

PMID- 20822253
TI  - Bayesian evaluation of inequality and equality constrained hypotheses for
      contingency tables.
AB  - In this article, a Bayesian model selection approach is introduced that can
      select the best of a set of inequality and equality constrained hypotheses for
      contingency tables. The hypotheses are presented in terms of cell probabilities
      allowing researchers to test (in)equality constrained hypotheses in a format that
      is directly related to the data. The proposed method is investigated by several
      simulation studies and shows good performance. Software that allows researchers
      to apply the Bayesian approach to their own data is also provided.

PMID- 20822254
TI  - How often is prep close to the true replication probability?
AB  - Largely due to dissatisfaction with the standard null hypothesis significance
      testing procedure, researchers have begun to consider alternatives. For example,
      Killeen (2005a) has argued that researchers should calculate prep that is
      purported to indicate the probability that, if the experiment in question were
      replicated, the obtained finding would be in the same direction as the original
      finding. However, Killeen also seems to indicate that rather than being the
      probability of replication, prep is actually the probability of obtaining a
      finding whereby the experimental group mean exceeds the control group mean. Our
      goal was to determine the relative frequency with which obtained prep statistics
      are close to true replication probabilities. Regardless of which way prep is
      defined, our simulations show that it is unlikely to be close to the true value
      unless both the population effect magnitude and the sample size are uncommonly
      large. The definitional problem in combination with the inaccuracy under either
      interpretation, constitutes an important challenge for those who espouse the
      routine computation of prep statistics.

PMID- 20822255
TI  - Structural invariance and age-related performance differences in face cognition.
AB  - Perceiving and memorizing faces swiftly and correctly are important social
      competencies. The organization of these interpersonal abilities and how they
      change across the life span are still poorly understood. We investigated changes
      in the mean and covariance structure of face cognition abilities across the adult
      life span. A sample of 448 participants, with age ranging from 18 to 88 years,
      completed a battery of 15 face cognition tasks. After establishing a measurement
      model of face cognition that distinguishes between face perception, face memory,
      and the speed of face cognition, we used multiple group models and age-weighted
      measurement models to explore age-related changes. The modeling showed that the
      loadings and intercepts of all measures are age invariant. The factor means
      showed substantial decrements with increasing age. Age-related decrements in
      performance were strongest for the speed of face cognition but were also salient
      for face perception and face memory. The onset of age decrements is apparent in
      the 60s for face perception, in the late 40s for face memory, and in the early
      30s for speed of face cognition. Implications of these findings on a theoretical
      and methodological level are discussed, and potential consequences for applied
      settings are considered.

PMID- 20822257
TI  - Use it or lose it? Wii brain exercise practice and reading for domain knowledge.
AB  - We investigated the training effects and transfer effects associated with 2
      approaches to cognitive activities (so-called brain training) that might mitigate
      age-related cognitive decline. A sample of 78 adults between the ages of 50 and
      71 completed 20 one-hr training sessions with the Nintendo Wii Big Brain Academy
      software over the course of 1 month and, in a second month, completed 20 one-hr
      reading sessions with articles on 4 different current topics (order of assignment
      was counterbalanced for the participants). An extensive battery of cognitive and
      perceptual speed ability measures was administered before and after each month of
      cognitive training activities, along with a battery of domain-knowledge tests.
      Results indicated substantial improvements on the Wii tasks, somewhat less
      improvement on the domain knowledge tests, and practice-related improvements on 6
      of the 10 ability tests. However, there was no significant transfer of training
      from either the Wii practice or the reading tasks to measures of cognitive and
      perceptual speed abilities. Implications for these findings are discussed in
      terms of adult intellectual development and maintenance.

PMID- 20822256
TI  - Associative deficit in recognition memory in a lifespan sample of healthy adults.
AB  - Advanced age is associated with decrements in episodic memory, which are more
      pronounced in memory for associations than for individual items. The associative
      deficit hypothesis (ADH) states that age differences in recognition memory
      reflect difficulty in binding components of a memory episode and retrieving bound
      units. To date, ADH has received support only in studies of extreme age groups,
      and the influence of sex, education, and health on age-related associative
      deficit is unknown. We address those issues using a verbal paired-associate yes
      no recognition paradigm on a lifespan sample of 278 healthy, well-educated
      adults. In accord with the ADH, greater age was associated with lower hit and
      greater false alarm rates and more liberal response bias on associative
      recognition tests. Women outperformed men on recognition of items and
      associations, but among normotensive participants, women outperformed men only on
      memory for associations and not on item recognition. Thus, although supporting
      ADH in a large lifespan sample of healthy adults, the findings indicate that the
      effect may be partially driven by an age-related increase in liberal bias in
      recognition of associations. Sex differences and health factors may modify the
      associative deficit regardless of age.

PMID- 20822258
TI  - The latent structure of dietary restraint, body dissatisfaction, and drive for
      thinness: a series of taxometric analyses.
AB  - Although the latent structure of various eating disorders has been explored in
      previous studies, no published studies have examined the latent structure of
      theoretically relevant variables that have been shown to cut across eating
      disorder diagnoses. The current study examined 3 such variables (dietary
      restraint, body dissatisfaction, and drive for thinness) among undergraduate
      women using the taxometric method. The 5 items from the Eating Disorders
      Examination Questionnaire's Dietary Restraint subscale were used as dietary
      restraint indicators, whereas items from the Eating Disorders Inventory Body
      Dissatisfaction and Drive for Thinness subscales were used as indicators of body
      dissatisfaction and drive for thinness, respectively. As hypothesized, MAXCOV
      (maximum covariance) and MAMBAC (mean above minus below a cut) analyses suggested
      that all 3 variables are dimensional; therefore, individuals with high levels of
      reported dietary restraint, body dissatisfaction, and drive for thinness appear
      to differ in degree, but not in kind, from those with lower levels. Implications
      for prevention, assessment, classification, and treatment are discussed.

PMID- 20822259
TI  - Investigation of the factor structure of the Wechsler Adult Intelligence Scale-
      Fourth Edition (WAIS-IV): exploratory and higher order factor analyses.
AB  - The present study examined the factor structure of the Wechsler Adult
      Intelligence Scale--Fourth Edition (WAIS-IV; D. Wechsler, 2008a) standardization
      sample using exploratory factor analysis, multiple factor extraction criteria,
      and higher order exploratory factor analysis (J. Schmid & J. M. Leiman, 1957) not
      included in the WAIS-IV Technical and Interpretation Manual (D. Wechsler, 2008b).
      Results indicated that the WAIS-IV subtests were properly associated with the
      theoretically proposed first-order factors, but all but one factor-extraction
      criterion recommended extraction of one or two factors. Hierarchical exploratory
      analyses with the Schmid and Leiman procedure found that the second-order g
      factor accounted for large portions of total and common variance, whereas the
      four first-order factors accounted for small portions of total and common
      variance. It was concluded that the WAIS-IV provides strong measurement of
      general intelligence, and clinical interpretation should be primarily at that
      level.

PMID- 20822260
TI  - Development and validation of an attributional style questionnaire for
      adolescents.
AB  - We describe the development and psychometric characteristics of a new version of
      the Attributional Style Questionnaire (ASQ; Seligman, Abramson, Semmell, & Von
      Baeyer, 1979)--a version called the Attributional Style Questionnaire for
      Adolescents (ASQ-A)--using 3 samples (Ns = 547, 438, and 240) of Spanish
      secondary school students. In Study 1, the initial pool of 87 items was reduced
      to 54. Study 2 further analyzed the 54 scale items and revealed that the
      Internality, Stability, and Globality subscale scores had good reliability, good
      factorial construct validity, and satisfactory associations with maladaptive mood
      ratings. In Study 3, the regression analyses showed good and specific predictive
      validities of ASQ-A subscales for the attributions that the adolescents made
      about a particular real-life stressful situation. Study 4 showed that over an 8
      month period the changes in the Stability and Globality subscales depended on the
      intensity of stressful life events experienced in this period. Overall, the
      studies revealed that the new ASQ-A served as an appropriate instrument to assess
      attributional style in adolescents.

PMID- 20822261
TI  - A new look at the big five factor structure through exploratory structural
      equation modeling.
AB  - NEO instruments are widely used to assess Big Five personality factors, but
      confirmatory factor analyses (CFAs) conducted at the item level do not support
      their a priori structure due, in part, to the overly restrictive CFA assumptions.
      We demonstrate that exploratory structural equation modeling (ESEM), an
      integration of CFA and exploratory factor analysis (EFA), overcomes these
      problems with responses (N = 3,390) to the 60-item NEO-Five-Factor Inventory: (a)
      ESEM fits the data better and results in substantially more differentiated (less
      correlated) factors than does CFA; (b) tests of gender invariance with the 13
      model ESEM taxonomy of full measurement invariance of factor loadings, factor
      variances-covariances, item uniquenesses, correlated uniquenesses, item
      intercepts, differential item functioning, and latent means show that women score
      higher on all NEO Big Five factors; (c) longitudinal analyses support measurement
      invariance over time and the maturity principle (decreases in Neuroticism and
      increases in Agreeableness, Openness, and Conscientiousness). Using ESEM, we
      addressed substantively important questions with broad applicability to
      personality research that could not be appropriately addressed with the
      traditional approaches of either EFA or CFA.

PMID- 20822262
TI  - Psychometric properties of the MMPI-2-RF Somatic Complaints (RC1) scale.
AB  - The MMPI-2 Restructured Form (MMPI-2-RF; Tellegen & Ben-Porath, 2008) was
      designed to be psychometrically superior to its MMPI-2 counterpart. However, the
      test has yet to be extensively evaluated in diverse clinical settings. The
      purpose of this study was to examine the psychometric properties of the MMPI-2-RF
      Somatic Complaints (RC1) scale in a clinically relevant population. Participants
      were 399 patients diagnosed with either epilepsy or psychogenic nonepileptic
      seizures on the basis of video-electroencephalograph monitoring. The internal
      structure of the MMPI-2-RF was evaluated using taxometric, confirmatory factor
      analysis, and item response theory procedures. Data from 4 content-specific
      scales directly related to RC1 (Malaise, Gastrointestinal Complaints, Head Pain
      Complaints, and Neurological Complaints) indicated that the latent construct of
      somatization is a dimensional variable with a bifactor structure. However,
      consistent with the scale's construction, a unidimensional model also provided
      adequate fit. A 2-parameter logistic item response theory model better accounted
      for observed item responses than did 1- or 3-parameter models. Results suggest
      that the RC1 scale is most precise for T score estimates between 55 and 90.
      Overall, the scale appears to be well suited for the assessment of somatization.

PMID- 20822263
TI  - Development and validation of culture-specific Variable Response Inconsistency
      and True Response Inconsistency scales for use with the Korean MMPI-2.
AB  - In response to the concern that Minnesota Multiphasic Personality Inventory-2
      (MMPI-2; J. N. Butcher, W. Dahlstrom, J. R. Graham, A. Tellegen, & B. Kaemmer,
      1989; J. N. Butcher et al., 2001) Variable Response Inconsistency (VRIN) and True
      Response Inconsistency (TRIN) score invalidity criteria recommended for use with
      American samples results in an excessive number of exclusions in Asian samples
      (F. M. Cheung, W. Z. Song, & J. X. Zhang, 1996), we examined the cross cultural
      equivalence of the original VRIN and TRIN scales, and developed and validated
      Korean-specific VRIN and TRIN scales with Korean adult normative, clinical, and
      college samples. Although the results from item pair correlation analyses
      suggested the superiority of the Korean VRIN and TRIN over the original VRIN and
      TRIN, the mean comparison results and classification accuracy statistics using
      data with varying degrees of randomly inserted true and/or false responses did
      not reveal a strong advantage of one version over the other. We present and
      discuss plausible causes of the findings.

PMID- 20822264
TI  - The Process of Retirement Planning Scale (PRePS): development and validation.
AB  - Although a substantial proportion of the western population is approaching
      retirement age, little is known about how they are preparing for the future. Much
      attention has been paid to the consumption of educational material and retirement
      wealth in the present literature, but the process of retirement planning has been
      ignored. S. L. Friedman and E. K. Scholnick's (1997) theoretical model provided
      the basis for a comprehensive measure of retirement planning. According to their
      process theory, individuals develop an understanding of the problem, set goals,
      make a decision to start preparing, and finally undertake the behaviors needed to
      fulfill their goals. Fifty-two items were developed to assess each stage of the
      planning process for financial, health, lifestyle, and psychosocial retirement
      planning. These were tested on a population sample of 1,449 New Zealanders aged
      49-60. Confirmatory factor analysis, bivariate correlations, and hierarchical
      regression provided support for the valid use of the measure. Necessary
      antecedents, such as the tendency to look to the future, and locus of control
      were significantly related to the Process of Retirement Planning Scale (PRePS).
      The PRePS also outperformed retirement planning measures used in the Health and
      Retirement Study (F. T. Juster & R. Suzman, 1995) after controlling for
      socioeconomic and psychological variables. This measure will enable social policy
      makers to determine which stages of retirement planning require support and
      intervention. The PRePS will also help to determine which domains of retirement
      planning predict well-being in later life and the factors which differentiate
      those who are planning from those who are not.

PMID- 20822265
TI  - Combining major life events and recurrent hassles in the assessment of stress in
      Chinese adolescents: preliminary evidence.
AB  - Major life events and hassles have been considered 2 distinct constructs in the
      measurement of stress. Research also shows that chronic events are more impactful
      than time-limited ones. This study reports a new approach to measuring stress in
      which major life events are combined with recurrent hassles to form a single
      index--the Adolescent Stress Index (ASI). High school students (N = 365) in Hong
      Kong responded twice at a 3-month interval to measures of major life events and
      hassles, the ASI, and measures of physical and depressive symptoms. Data were
      analyzed using structural equation modeling. Results showed that the ASI
      predicted symptoms concurrently and prospectively above and beyond the effects of
      existing measures of major life events and hassles. The ASI is a viable
      instrument for documenting the cumulative impact of major and minor events in the
      lives of adolescents.

PMID- 20822266
TI  - The impact of NEO PI-R gender norms on the assessment of personality disorder
      profiles.
AB  - Many personality assessment inventories provide gender-specific norms to allow
      comparison of an individual's standing relative to others of the same gender. In
      some cases, this means that an identical raw score produces standardized scores
      that differ notably depending on whether the respondent is male or female. Thus,
      an important question is whether unisex-normed scores or gender-normed scores
      more validly assess personality. Gender-normed and unisex-normed scores from the
      NEO Personality Inventory--Revised (P. T. Costa & R. R. McCrae, 1992) were
      examined in a large clinical sample, using 2 measures of personality disorder as
      validating criteria. Gender-normed scores did not obtain significantly higher
      correlations. In fact, for 2 personality disorders (antisocial and narcissistic),
      gender-normed scores yielded significantly lower correlations, suggesting that
      personality disorder pathology relates most closely to one's absolute level of a
      personality trait, rather than one's standing relative to others of the same
      gender. Ramifications of this finding for personality research and clinical
      assessment are discussed.

PMID- 20822267
TI  - Attention-deficit/hyperactivity disorder symptoms in preschool children:
      examining psychometric properties using item response theory.
AB  - Clear and empirically supported diagnostic symptoms are important for proper
      diagnosis and treatment of psychological disorders. Unfortunately, the symptoms
      of many disorders presented in the Diagnostic and Statistical Manual of Mental
      Disorders (4th ed., text rev.; DSM-IV-TR; American Psychiatric Association, 2000)
      lack sufficient psychometric evaluation. In this study, an item response theory
      (IRT) analysis was applied to ratings of the 18 attention-deficit/hyperactivity
      disorder (ADHD) symptoms in 268 preschool children. Children (55% boys, 45%
      girls) in this sample ranged in age from 37 to 74 months; 80.4% were identified
      as African American, 15.1% as Caucasian, and 4.5% as other ethnicity. Dichotomous
      and polytomous scoring methods for rating ADHD symptoms were compared and
      psychometric properties of these symptoms were calculated. Symptom-level analyses
      revealed that, in general, the current symptoms provided useful information in
      diagnosing ADHD in preschool children; however, several symptoms provided
      redundant information and should be examined further.

PMID- 20822268
TI  - Psychometric characteristics and clinical correlates of NEO-PI-R fearless
      dominance and impulsive antisociality in the Collaborative Longitudinal
      Personality Disorders Study.
AB  - This study evaluates the validity of derived measures of the psychopathic
      personality traits of Fearless Dominance and Impulsive Antisociality from the NEO
      Personality Inventory-Revised (NEO-PI-R; Costa & McCrae, 1992) using data from
      the Collaborative Longitudinal Personality Disorders Study (baseline N = 733).
      These 3 issues were examined: (a) the stability of the measures over a 10-year
      interval, (b) their criterion-related validity, and (c) their incremental
      validity relative to an alternative NEO-PI-R profile-rating approach for
      assessing psychopathy. NEO-PI-R Fearless Dominance and Impulsive Antisociality
      scales were relatively stable across 10 years and demonstrated differential
      associations with measures of personality pathology and psychopathology generally
      consistent with past research and theoretical considerations. Moreover, these
      measures demonstrated an appreciable degree of incremental validity over the NEO
      PI-R profile-rating approach.

PMID- 20822269
TI  - Do core interpersonal and affective traits of PCL-R psychopathy interact with
      antisocial behavior and disinhibition to predict violence?
AB  - The utility of psychopathy measures in predicting violence is largely explained
      by their assessment of social deviance (e.g., antisocial behavior;
      disinhibition). A key question is whether social deviance interacts with the core
      interpersonal-affective traits of psychopathy to predict violence. Do core
      psychopathic traits multiply the (already high) risk of violence among
      disinhibited individuals with a dense history of misbehavior? This meta-analysis
      of 32 effect sizes (N = 10,555) tested whether an interaction between the
      Psychopathy Checklist-Revised (PCL-R; R. D. Hare, 2003) Interpersonal-Affective
      and Social Deviance scales predicted violence beyond the simple additive effects
      of each scale. Results indicate that Social Deviance is more uniquely predictive
      of violence (d = .40) than Interpersonal-Affective traits (d = .11), and these
      two scales do not interact (d = .00) to increase power in predicting violence. In
      fact, Social Deviance alone would predict better than the Interpersonal-Affective
      scale and any interaction in 81% and 96% of studies, respectively. These findings
      have fundamental practical implications for risk assessment and theoretical
      implications for some conceptualizations of psychopathy.

PMID- 20822270
TI  - Causal client models in selecting effective interventions: a cognitive mapping
      study.
AB  - An important reason to choose an intervention to treat psychological problems of
      clients is the expectation that the intervention will be effective in alleviating
      the problems. The authors investigated whether clinicians base their ratings of
      the effectiveness of interventions on models that they construct representing the
      factors causing and maintaining a client's problems. Forty clinical child
      psychologists drew causal models and rank ordered interventions according to
      their expected effectiveness for 2 cases. The authors found that different
      clinicians constructed different causal models for the same client. Also, the
      authors found low to moderate agreement about the effectiveness of different
      interventions. Nevertheless, the authors could predict clinicians' ratings of
      effectiveness from their individual causal models.

PMID- 20822271
TI  - Therapeutic assessment for preadolescent boys with oppositional defiant disorder:
      a replicated single-case time-series design.
AB  - The Therapeutic Assessment (TA) model is a relatively new treatment approach that
      fuses assessment and psychotherapy. The study examines the efficacy of this model
      with preadolescent boys with oppositional defiant disorder and their families. A
      replicated single-case time-series design with daily measures is used to assess
      the effects of TA and to track the process of change as it unfolds. All 3
      families benefitted from participation in TA across multiple domains of
      functioning, but the way in which change unfolded was unique for each family.
      These findings are substantiated by the Behavior Assessment System for Children
      (Reynolds & Kamphaus, 2004). The TA model is shown to be an effective treatment
      for preadolescent boys with oppositional defiant disorder and their families.
      Further, the time-series design of this study illustrated how this empirically
      grounded case-based methodology reveals when and how change unfolds during
      treatment in a way that is usually not possible with other research designs.

PMID- 20822272
TI  - The latent symptom structure of the Beck Depression Inventory-II in outpatients
      with major depression.
AB  - The Beck Depression Inventory-II (BDI-II) is a self-report instrument frequently
      used in clinical and research settings to assess depression severity. Although
      investigators have examined the factor structure of the BDI-II, a clear consensus
      on the best fitting model has not yet emerged, resulting in different
      recommendations regarding how to best score and interpret BDI-II results. In the
      current investigation, confirmatory factor analysis was used to evaluate
      previously identified models of the latent symptom structure of depression as
      assessed by the BDI-II. In contrast to previous investigations, we utilized a
      reliably diagnosed, homogenous clinical sample, composed only of patients with
      major depressive disorder (N = 425)--the population for whom this measure of
      depression severity was originally designed. Two 3-factor models provided a good
      fit to the data and were further evaluated by means of factor associations with
      an external, interviewer-rated measure of depression severity. The results
      contribute to a growing body of evidence for the Ward (2006) model, including a
      General (G) depression factor, a Somatic (S) factor, and a Cognitive (C) factor.
      The results also support the use of the BDI-II total scale score. Research
      settings may wish to model minor factors to remove variance extraneous to
      depression where possible.

PMID- 20822273
TI  - Assessment of dysregulated children using the Child Behavior Checklist: a
      receiver operating characteristic curve analysis.
AB  - Disorders of self-regulatory behavior are common reasons for referral to child
      and adolescent clinicians. Here, the authors sought to compare 2 methods of
      empirically based assessment of children with problems in self-regulatory
      behavior. Using parental reports on 2,028 children (53% boys) from a U.S.
      national probability sample of the Child Behavior Checklist (CBCL; T. M.
      Achenbach & L. A. Rescorla, 2001), the receiver operating characteristic curve
      analysis was applied to compare scores on the Posttraumatic Stress Problems Scale
      (PTSP) of the CBCL with the CBCL Dysregulation Profile (DP), identified using
      latent class analysis of the Attention Problems, Aggressive Behavior, and
      Anxious/Depressed scales of the CBCL. The CBCL-PTSP score demonstrated an area
      under the curve of between .88 and .91 for predicting membership in the CBCL-DP
      profile for boys and for girls. These findings suggest that the CBCL-PTSP, which
      others have shown does not uniquely identify children who have been traumatized,
      does identify the same profile of behavior as the CBCL-DP. Therefore, the authors
      recommend renaming the CBCL-PTSP the Dysregulation Short Scale and provide some
      guidelines for the use of the CBCL-DP scale and the CBCL-PTSP in clinical
      practice.

PMID- 20822274
TI  - Psychometric comparisons of the Pictorial Child Behavior Checklist with the
      standard version of the instrument.
AB  - The low level of literacy and lack of language proficiency possessed by some
      immigrants from low socioeconomic status backgrounds create communication
      barriers in the healthcare setting, thus interfering with their ability to access
      appropriate medical care and their subsequent participation in medical research.
      Adding pictorial descriptions to questionnaires appears to improve patient
      response when literacy levels are low. Psychometric results from 4 studies using
      a pictorial version of the Child Behavior Checklist (Pictorial Child Behavior
      Checklist, or PCBCL) to assess behavioral and emotional problems in children from
      low-income Hispanic families attending hospital-based pediatric practices are
      reported here. The 2 form versions (the original Child Behavior Checklist, or
      CBCL, vs. the PCBCL), which were randomly assigned, manifested comparable test
      retest reliability (Study 1), alternate-form reliability (Study 2), and mean
      problem scores (Study 3). The PCBCL was also comparable to the CBCL in
      discriminating between community children attending regular pediatric clinics and
      children attending an outpatient psychiatric clinic (Study 4). Thus, the PCBCL
      yielded results that were comparable to those obtained with the CBCL, indicating
      that it may be a viable alternative for parents confronting communication
      barriers due to low literacy levels.

PMID- 20822275
TI  - The latent structure of childhood aggression: a taxometric analysis of self
      reported and teacher-rated aggression in Israeli schoolchildren.
AB  - The purpose of this study was to determine whether the latent structure of
      childhood aggression, like the latent structure of adult antisocial behavior, is
      dimensional. One thousand and five Israeli schoolchildren completed a translation
      of the Buss-Perry Aggression Questionnaire (AQ; Buss & Perry, 1992) and were
      rated by their homeroom teachers on the Eyberg Child Behavior Inventory (ECBI;
      Robinson, Eyberg, & Ross, 1980). The AQ Physical Aggression and Verbal Aggression
      scales were combined to form the 1st indicator, the AQ Anger and Hostility scales
      were combined to form the 2nd indicator, the 10-item ECBI Oppositional Defiant
      Behavior Toward Adults scale composed the 3rd indicator, and the 8-item ECBI
      Conduct Problem Behavior scale composed the 4th indicator. Subjecting these
      indicators to taxometric analysis revealed consistent support for dimensional
      latent structure in the full sample as well as in 5 of the 6 subsamples.
      Childhood aggression, it would seem, differs quantitatively along a dimension
      (degree of aggression) rather than bifurcating into qualitatively distinct
      categories (aggressive vs. nonaggressive).

PMID- 20822276
TI  - Understanding psychopathy through an evaluation of interpersonal behavior:
      testing the factor structure of the interpersonal measure of psychopathy in a
      large sample of jail detainees.
AB  - Interpersonal characteristics are core features of the psychopathy construct
      which have a unique pattern of correlations with a variety of external
      correlates. To improve the assessment of interpersonal traits, the current study
      evaluated the internal structure of the Interpersonal Measure of Psychopathy (IM
      P) through exploratory and confirmatory factor analyses (CFA) in a large sample
      of jail inmates. A 17-item, 3-factor (Dominance, Grandiosity, and Boundary
      Violations) structure evidenced good fit in European American inmates. A second
      CFA demonstrated good fit for this structure in a sample of African American
      inmates. Moreover, a multigroup CFA indicated structural invariance between
      European and African American inmates. External validity was tested and
      demonstrated through positive correlations between IM-P factor scores and
      Psychopathy Checklist--Revised total and facet scores (R. D. Hare, 2003) and
      antisocial personality disorder symptoms and diagnoses. Modest correlations
      between Grandiosity scores and scores on the Shipley Institute of Living Scale-
      Revised (R. A. Zachary, 1994) were also observed. Finally, a step-down
      hierarchical regression was conducted to test for racial bias of the IM-P factor
      scores in relation to external correlates. Little evidence was found for slope
      bias, but there was evidence of intercept bias for some analyses. Implications
      and advantages of assessing psychopathy through a comprehensive evaluation of
      interpersonal traits are discussed.

PMID- 20822277
TI  - Seeing the forest for the trees: prevalence of low scores on the Wechsler
      Intelligence Scale for Children, fourth edition (WISC-IV).
AB  - Low scores across a battery of tests are common in healthy people and vary by
      demographic characteristics. The purpose of the present article was to present
      the base rates of low scores for the Wechsler Intelligence Scale for Children,
      fourth edition (WISC-IV; D. Wechsler, 2003). Participants included 2,200 children
      and adolescents between 6 and 16 years of age from the WISC-IV U.S.
      standardization sample. Measures considered in the base rates analyses included
      the 10 core subtests and the 4 index scores. Analyses were conducted for the
      entire standardization sample as well as stratified by different classifications
      of intelligence and different years of parental education. In the total sample,
      it is uncommon to have 6 or more subtest scores or 2 or more Index scores <or=
      9th percentile. The prevalence of low scores typically increased with lesser
      intelligence and fewer years of parental education (e.g., children with below
      average intelligence were 75 times more likely than children with above
      intelligence to have at least one impaired subtest score). Consistent with
      existing studies of the base rates of low scores, some low scores on the WISC-IV
      were common in children and adolescents, and the frequency was related to a
      child's level of intelligence and parental education.

PMID- 20822278
TI  - A proposal for evaluating cognition in assertiveness.
AB  - This article presents the development process and initial psychometric features
      of an instrument for evaluating cognition in assertiveness. This is an essential
      social skill for adolescent development and seems to encompass emotional,
      behavioral, and cognitive aspects. The instrument was created by combining both
      empirical and theoretical methods for item construction, aiming to evaluate the
      cognitive realm of assertiveness. A sample of 996 adolescent students was used to
      test for reliability and validity. Results indicate good psychometric properties.
      The instrument is composed of 4 subscales: Outer Emotional Support, Functional
      Personal Ability, Interpersonal Management, and Affective Personal Ability. The
      Assertive Interpersonal Schema Questionnaire may potentially be a useful tool in
      the diagnosis of, understanding of, and development of a treatment plan for
      individuals with persistent difficulties in social events.

PMID- 20822279
TI  - Heterogeneity in the latent structure of PTSD symptoms among Canadian veterans.
AB  - The current study used factor mixture modeling to identify heterogeneity (i.e.,
      latent classes) in 2 well-supported models of posttraumatic stress disorder's
      (PTSD) factor structure. Data were analyzed from a clinical sample of 405
      Canadian veterans evaluated for PTSD. Results were consistent with our
      hypotheses. Each PTSD factor model was best represented by 2 latent classes of
      participants, differing with respect to PTSD symptom severity. Furthermore,
      classes were most strongly distinguished by factor scores related to emotional
      numbing or dysphoria. For both factor models, class membership was significantly
      predicted by age and depression diagnosis. Implications of these findings are
      discussed.

PMID- 20822281
TI  - The Aberrant Salience Inventory: a new measure of psychosis proneness.
AB  - Aberrant salience is the unusual or incorrect assignment of salience,
      significance, or importance to otherwise innocuous stimuli and has been
      hypothesized to be important for psychosis and psychotic disorders such as
      schizophrenia. Despite the importance of this concept in psychosis research, no
      questionnaire measures are available to assess aberrant salience. The current
      research describes 4 studies designed to develop and validate the Aberrant
      Salience Inventory (ASI) as a measure of aberrant salience. In Study 1, an
      overinclusive item pool was subjected to an exploratory factor analysis, and
      items were kept or discarded based on factor loadings. In Study 2, the 5-factor
      structure of the ASI was confirmed with a confirmatory factor analysis, and a 2nd
      order factor analysis found evidence consistent with a single higher order
      factor. Study 2 also provided support for the scale score's convergent validity
      as the ASI was strongly associated with psychosis-proneness measures and
      dissociation measures and moderately correlated with measures associated with
      levels of dopamine. This study also provided support for its discriminant
      validity as the ASI was only weakly associated with social anhedonia. Study 3
      found that participants with elevated psychosis proneness had increased ASI
      scores, but in contrast, participants with elevated social anhedonia had similar
      scores to comparison participants. Finally, Study 4 found that participants with
      a history of psychosis had elevated ASI scores compared to a psychiatric
      comparison group. Overall, the ASI demonstrated sound psychometric properties and
      may be useful for measuring aberrant salience and psychosis proneness in clinical
      and nonclinical samples.

PMID- 20822280
TI  - Factorial validity of the Texas Revised Inventory of Grief-Present scale among
      bereaved older adults.
AB  - The Texas Revised Inventory of Grief-Present scale (TRIG-Present) is one of the
      most widely used grief measures; however, researchers have only empirically
      examined the validity and underlying factor structure of TRIG-Present scores in a
      few studies. Hence, in the present investigation, we sought to examine the
      factorial validity of the TRIG-Present (those scores that index current grief)
      among 2 samples of bereaved older adults--a community-dwelling sample of 162
      individuals who experienced a diverse set of losses in terms of relationship to
      the deceased and time since loss, and a recently widowed sample of 212
      individuals who were assessed at 2-months and 12-months postloss. Across both
      samples, we found support for a 3-factor model, composed of clusters of items
      representing Emotional Response, Thoughts, and Nonacceptance regarding a loss.
      Additionally, this 3-factor model exhibited significant invariance from 2-months
      to 12-months postloss in the recently widowed sample. Analyses examining the
      convergent validity of these 3 factors also suggest that this conceptualization
      of the TRIG-Present could have practical advantages and potentially influence the
      way in which clinicians and/or researchers assess grief and evaluate bereavement
      interventions.

PMID- 20822283
TI  - Screening for depressive disorders using the Mood and Anxiety Symptoms
      Questionnaire Anhedonic Depression Scale: a receiver-operating characteristic
      analysis.
AB  - The present study examined the utility of the anhedonic depression scale from the
      Mood and Anxiety Symptoms Questionnaire (MASQ-AD scale) as a way to screen for
      depressive disorders. Using receiver-operating characteristic analysis, we
      examined the sensitivity and specificity of the full 22-item MASQ-AD scale, as
      well as the 8- and 14-item subscales, in relation to both current and lifetime
      Diagnostic and Statistical Manual of Mental Disorders (4th ed.) depressive
      disorder diagnoses in two nonpatient samples. As a means of comparison, the
      sensitivity and specificity of a measure of a relevant personality dimension,
      Neuroticism, was also examined. Results from both samples support the clinical
      utility of the MASQ-AD scale as a means of screening for depressive disorders.
      Findings were strongest for the MASQ-AD 8-item subscale and when predicting
      current depression status. Furthermore, the MASQ-AD 8-item subscale outperformed
      the Neuroticism measure under certain conditions. The overall usefulness of the
      MASQ-AD scale as a screening device is discussed, as are possible cutoff scores
      for use in research.

PMID- 20822284
TI  - A reexamination of the factor structure of the Center for Epidemiologic Studies
      Depression Scale: is a one-factor model plausible?
AB  - The Center for Epidemiologic Studies Depression Scale (CES-D) is one of the most
      widely used measures of depressive symptoms in research today. The original
      psychometric work in support of the CES-D (Radloff, 1977) described a 4-factor
      model underlying the 20 items on the scale. Despite a long history of evidence
      supporting this structure, researchers routinely report single-number summaries
      from the CES-D. The research described in this article examines the plausibility
      of 1-factor model using an initial sample of 595 subjects and a cross-validation
      sample of 661. After comparing a series of models found in the literature or
      suggested by analyses, we determined that the good fit of the 4-factor model is
      mostly due to its ability to model excess covariance associated with the 4
      reverse-scored items. A 2-factor model that included a general depression factor
      and a positive wording method factor loading only on those 4 items had fit that
      was nearly as good as the original 4-factor model. We conclude that although a 1
      factor model may not be the best model for the full 20-item CES-D, it is at least
      plausible. If a unidimensional set of items is required (e.g., for a
      unidimensional item response theory analysis), by dropping 5 items, we were able
      to find a 1-factor model that had very similar fit to the 4-factor model with the
      original 20 items.

PMID- 20822285
TI  - Adjudicative competence: evidence that impairment in "rational understanding" is
      taxonic.
AB  - In Dusky v. United States (1960), the U.S. Supreme Court articulated 3 abilities
      that determine a criminal defendant's competence to stand trial: He or she must
      be able to consult with counsel, have a factual understanding of the proceedings,
      and have a rational understanding of the proceedings. Although the legal
      determination of a defendant's competence involves a dichotomous judgment, the
      latent structures of the constructs that underlie the abilities articulated in
      Dusky are unknown. The current study focused on the rational understanding prong
      of the Dusky standard. We hypothesized that, whereas factual knowledge of the
      legal system and ability to assist counsel may fall on a continuum, plausible
      (i.e., rational) beliefs about legal proceedings may be dichotomous in nature.
      Taxometric analyses of the Appreciation scale of the MacArthur Competence
      Assessment Tool--Criminal Adjudication, with a sample of 721 defendants, provided
      support for a taxonic structure.

PMID- 20822286
TI  - The regulatory function of self-esteem: testing the epistemic and acceptance
      signaling systems.
AB  - The authors draw on sociometer theory (e.g., Leary, 2004) and self-verification
      theory (e.g., Swann, 1997) to propose an expanded model of the regulatory
      function of self-esteem. The model suggests that people not only possess an
      acceptance signaling system that indicates whether relational value is high or
      low but also possess an epistemic signaling system that indicates whether social
      feedback is consistent or inconsistent with chronic perceived relational value
      (i.e., global self-esteem). One correlational study and 5 experiments, with
      diverse operationalizations of social feedback, demonstrated that the epistemic
      signaling system responds to self-esteem consistent or inconsistent relational
      value feedback with increases or deceases in epistemic certainty. Moreover,
      Studies 3-6 demonstrated that the acceptance and epistemic signaling systems
      respond uniquely to social feedback. Finally, Studies 5 and 6 provide evidence
      that the epistemic signaling system is part of a broader self-regulatory system:
      Self-esteem inconsistent feedback caused cognitive efforts to decrease the
      discrepancy between self-views and feedback and caused depleted self-regulatory
      capacity on a subsequent self-control task.

PMID- 20822287
TI  - Ovulation as a male mating prime: subtle signs of women's fertility influence
      men's mating cognition and behavior.
AB  - Women's reproductive fertility peaks for a few days in the middle of their cycle
      around ovulation. Because conception is most likely to occur inside this brief
      fertile window, evolutionary theories suggest that men possess adaptations
      designed to maximize their reproductive success by mating with women during their
      peak period of fertility. In this article, we provide evidence from 3 studies
      that subtle cues of fertility prime mating motivation in men, thus facilitating
      psychological and behavioral processes associated with the pursuit of a sexual
      partner. In Study 1, men exposed to the scent of a woman near peak levels of
      fertility displayed increased accessibility to sexual concepts. Study 2
      demonstrated that, among men who reported being sensitive to odors, scent cues of
      fertility triggered heightened perceptions of women's sexual arousal. Study 3
      revealed that, in a face-to-face interaction, high levels of female fertility
      were associated with a greater tendency for men to make risky decisions and to
      behaviorally mimic a female partner. Hence, subtle cues of fertility led to a
      cascade of mating-related processes-from lower order cognition to overt behavior
      that reflected heightened mating motivation. Implications for theories of goal
      pursuit, romantic attraction, and evolutionary psychology are discussed.

PMID- 20822288
TI  - Retraining attitudes and stereotypes to affect motivation and cognitive capacity
      under stereotype threat.
AB  - In a series of experiments, a retraining paradigm was used to test the effects of
      attitudes and stereotypes on individuals' motivation and cognitive capacity in
      stereotype-threatening contexts. Women trained to have a more positive math
      attitude exhibited increased math motivation (Study 1). This effect was not
      observed for men but was magnified among women when negative stereotypes were
      either primed subtly (Study 2) or indirectly reinforced (Study 3). Although
      attitudes had no effect on working memory capacity, women retrained to associate
      their gender with being good at math exhibited increased working memory capacity
      (Studies 3 and 4), which in turn mediated increased math performance (Study 4) in
      a stereotype-threatening context. Results suggest that although positive
      attitudes can motivate stigmatized individuals to engage with threatening
      domains, stereotypes need to be retrained to give them the cognitive capacity
      critical for success. Implications for interventions to reduce stereotype threat
      are discussed.

PMID- 20822290
TI  - The categorization-individuation model: an integrative account of the other-race
      recognition deficit.
AB  - The other-race effect (ORE), or the finding that same-race faces are better
      recognized than other-race faces, is one of the best replicated phenomena in face
      recognition. The current article reviews existing evidence and theory and
      proposes a new theoretical framework for the ORE, which argues that the effect
      results from a confluence of social categorization, motivated individuation, and
      perceptual experience. This categorization-individuation model offers not only a
      parsimonious account of both classic and recent evidence for category-based
      biases in face recognition but also links the ORE to broader evidence and theory
      in social cognition and face perception. Finally, the categorization
      individuation model makes a series of novel predictions for how the ORE can be
      exacerbated, attenuated, or even eliminated via perceptual and motivational
      processes, both by improving other-race recognition and by reducing same-race
      recognition. The authors propose that this new model for the ORE also leads to
      applied interventions that differ sharply from other theories of the ORE, while
      simultaneously providing an integrative theoretical framework for future research
      on the ORE.

PMID- 20822289
TI  - Representational explanations of "process" dissociations in recognition: the
      DRYAD theory of aging and memory judgments.
AB  - It is widely assumed that older adults suffer a deficit in the psychological
      processes that underlie remembering of contextual or source information. This
      conclusion is based in large part on empirical interactions, including disordinal
      ones, that reveal differential effects of manipulations of memory strength on
      recognition in young and old subjects. This article lays out an alternative
      theory that takes as a starting point the overwhelming evidence from the
      psychometric literature that the effects of age on memory share a single
      mediating influence. Thus, the theory assumes no differences between younger and
      older subjects other than a global difference in memory fidelity--that is, the
      older subjects are presumed to have less valid representations of events and
      objects than are young subjects. The theory is articulated through 3 major
      assumptions and implemented in a computational model, DRYAD, to simulate
      fundamental results in the literature on aging and recognition, including the
      very interactions taken to imply selective impairment in older people. The
      theoretical perspective presented here allows for a critical examination of the
      widely held belief that aging entails the selective disruption of particular
      memory processes.

PMID- 20822292
TI  - Democracy under uncertainty: the wisdom of crowds and the free-rider problem in
      group decision making.
AB  - We introduce a game theory model of individual decisions to cooperate by
      contributing personal resources to group decisions versus by free riding on the
      contributions of other members. In contrast to most public-goods games that
      assume group returns are linear in individual contributions, the present model
      assumes decreasing marginal group production as a function of aggregate
      individual contributions. This diminishing marginal returns assumption is more
      realistic and generates starkly different predictions compared to the linear
      model. One important implication is that, under most conditions, there exist
      equilibria where some, but not all, members of a group contribute, even with
      completely self-interested motives. An agent-based simulation confirmed the
      individual and group advantages of the equilibria in which behavioral asymmetry
      emerges from a game structure that is a priori perfectly symmetric for all agents
      (all agents have the same payoff function and action space but take different
      actions in equilibria). A behavioral experiment demonstrated that cooperators and
      free riders coexist in a stable manner in groups performing with the nonlinear
      production function. A collateral result demonstrated that, compared to a
      dictatorial decision scheme guided by the best member in a group, the
      majority/plurality decision rules can pool information effectively and produce
      greater individual net welfare at equilibrium, even if free riding is not
      sanctioned. This is an original proof that cooperation in ad hoc decision-making
      groups can be understood in terms of self-interested motivations and that,
      despite the free-rider problem, majority/plurality decision rules can function
      robustly as simple, efficient social decision heuristics.

PMID- 20822293
TI  - The robust beauty of ordinary information.
AB  - Heuristics embodying limited information search and noncompensatory processing of
      information can yield robust performance relative to computationally more complex
      models. One criticism raised against heuristics is the argument that complexity
      is hidden in the calculation of the cue order used to make predictions. We
      discuss ways to order cues that do not entail individual learning. Then we
      propose and test the thesis that when orders are learned individually, people's
      necessarily limited knowledge will curtail computational complexity while also
      achieving robustness. Using computer simulations, we compare the performance of
      the take-the-best heuristic--with dichotomized or undichotomized cues--to
      benchmarks such as the naive Bayes algorithm across 19 environments. Even with
      minute sizes of training sets, take-the-best using undichotomized cues excels.
      For 10 environments, we probe people's intuitions about the direction of the
      correlation between cues and criterion. On the basis of these intuitions, in most
      of the environments take-the-best achieves the level of performance that would be
      expected from learning cue orders from 50% of the objects in the environments.
      Thus, ordinary information about cues--either gleaned from small training sets or
      intuited--can support robust performance without requiring Herculean
      computations.

PMID- 20822294
TI  - Experimental renewal in human participants.
AB  - Two experiments with human participants are presented that differentiate renewal
      from other behavioral effects that can produce a response after extinction.
      Participants played a video game and learned to suppress their behavior when
      sensor stimuli predicted an attack. Contexts (A, B, & C) were provided by
      fictitious galaxies where the game play took place. In Experiment 1, participants
      who received conditioning in A, extinction in B, and testing in A showed some
      context specificity of conditioning during extinction and a recovery of
      suppression on test. Experiment 2 demonstrated recovery of extinguished
      responding when participants were conditioned in A, extinguished in B, and tested
      in C, a third, neutral context. The experiment also demonstrated that the context
      of extinction did not control performance by becoming inhibitory. Results are
      discussed in terms of mechanisms that can produce a response recovery after
      extinction. The experiments demonstrated a renewal effect: a response recovery
      that was not attributable to the contexts acting as simple conditioned stimuli
      and is the first work with human participants to conclusively do so.

PMID- 20822291
TI  - Neurally constrained modeling of perceptual decision making.
AB  - Stochastic accumulator models account for response time in perceptual decision
      making tasks by assuming that perceptual evidence accumulates to a threshold. The
      present investigation mapped the firing rate of frontal eye field (FEF) visual
      neurons onto perceptual evidence and the firing rate of FEF movement neurons onto
      evidence accumulation to test alternative models of how evidence is combined in
      the accumulation process. The models were evaluated on their ability to predict
      both response time distributions and movement neuron activity observed in monkeys
      performing a visual search task. Models that assume gating of perceptual evidence
      to the accumulating units provide the best account of both behavioral and neural
      data. These results identify discrete stages of processing with anatomically
      distinct neural populations and rule out several alternative architectures. The
      results also illustrate the use of neurophysiological data as a model selection
      tool and establish a novel framework to bridge computational and neural levels of
      explanation.

PMID- 20822295
TI  - Blocking of potentiation of latent inhibition.
AB  - We present a theory of latent inhibition based on the Pearce-Hall (Pearce & Hall,
      1980) model for classical conditioning. Its central features are (1) that the
      associability of a stimulus declines as it comes to predict its consequences and
      (2) that nonreinforced exposure to a stimulus engages an associative learning
      process that makes the stimulus an accurate predictor of its consequences (in
      this case, the occurrence of no event). A formalization of this theory is shown
      to accommodate the finding that preexposure in compound with another cue can
      potentiate latent inhibition to the target cue. It further predicts that
      preexposure to the added cue will eliminate the potentiation effect. An
      experiment using rats and the flavor-aversion procedure confirmed this
      prediction.

PMID- 20822296
TI  - The role of working memory in spatial S-R correspondence effects.
AB  - This study investigates the impact of working memory (WM) load on response
      conflicts arising from spatial (non) correspondence between irrelevant stimulus
      location and response location (Simon effect). The dominant view attributes the
      Simon effect to automatic processes of location-based response priming. The
      automaticity view predicts insensitivity of the Simon effect to manipulations of
      processing load. Four experiments investigated the role of spatial and verbal WM
      in horizontal and vertical Simon tasks by using a dual-task approach.
      Participants maintained different amounts of spatial or verbal information in WM
      while performing a horizontal or vertical Simon task. Results showed that high
      load generally decreased, and sometimes eliminated, the Simon effect. It is
      interesting to note that spatial load had a larger impact than verbal load on the
      horizontal Simon effect, whereas verbal load had a larger impact than spatial
      load on the vertical Simon effect. The results highlight the role of WM as the
      perception-action interface in choice-response tasks. Moreover, the results
      suggest spatial coding of horizontal stimulus-response (S-R) tasks, and verbal
      coding of vertical S-R tasks.

PMID- 20822297
TI  - Multiple mechanisms in the perception of face gender: Effect of sex-irrelevant
      features.
AB  - Effects of sex-relevant and sex-irrelevant facial features on the evaluation of
      facial gender were investigated. Participants rated masculinity of 48 male facial
      photographs and femininity of 48 female facial photographs. Eighty feature points
      were measured on each of the facial photographs. Using a generalized Procrustes
      analysis, facial shapes were converted into multidimensional vectors, with the
      average face as a starting point. Each vector was decomposed into a sex-relevant
      subvector and a sex-irrelevant subvector which were, respectively, parallel and
      orthogonal to the main male-female axis. Principal components analysis (PCA) was
      performed on the sex-irrelevant subvectors. One principal component was
      negatively correlated with both perceived masculinity and femininity, and another
      was correlated only with femininity, though both components were orthogonal to
      the male-female dimension (and thus by definition sex-irrelevant). These results
      indicate that evaluation of facial gender depends on sex-irrelevant as well as
      sex-relevant facial features.

PMID- 20822298
TI  - Canonical visual size for real-world objects.
AB  - Real-world objects can be viewed at a range of distances and thus can be
      experienced at a range of visual angles within the visual field. Given the large
      amount of visual size variation possible when observing objects, we examined how
      internal object representations represent visual size information. In a series of
      experiments which required observers to access existing object knowledge, we
      observed that real-world objects have a consistent visual size at which they are
      drawn, imagined, and preferentially viewed. Importantly, this visual size is
      proportional to the logarithm of the assumed size of the object in the world, and
      is best characterized not as a fixed visual angle, but by the ratio of the object
      and the frame of space around it. Akin to the previous literature on canonical
      perspective, we term this consistent visual size information the canonical visual
      size.

PMID- 20822299
TI  - Is this object balanced or unbalanced? Judgments are on the safe side.
AB  - Do we perceive correctly whether a 2-D object is balanced or unbalanced? What
      would be the cause of biased equilibrium judgments? In two psychometric studies,
      we varied independently the characteristics of the objects and the equilibrium
      states. First, we observed that observers were excessively sensitive to the
      eccentricity of the object top. Second, we found that the subjective transition
      from "staying upright" to "falling" occurred before the object would have lost
      balance according to physical laws. To determine the role of naive physics
      beliefs, we tested the effect of physical knowledge. Indeed, participants gave
      much less erroneous fall responses, once they were acquainted with the physical
      law. However, a slight bias remained that could not be attributed to an error in
      locating the position of the center of mass, as fall judgments occurred even when
      participants judged that the center of mass was above the object base. That is,
      participants seemed to act according to the principle that it is safer to judge
      that an object will fall though it would not, rather than making the opposite
      error.

PMID- 20822300
TI  - Diluting the burden of load: perceptual load effects are simply dilution effects.
AB  - The substantial distractor interference obtained for small displays when the
      target appears alone is reduced in large displays when the target is embedded
      among neutral letters. This finding has been interpreted as reflecting low-load
      and high-load processing, respectively, thereby supporting the theory of
      perceptual load (Lavie & Tsal, 1994). However, a possible alternative
      interpretation of this effect is that the distractor is similarly processed in
      both displays, yet its interference in the large ones is diluted by the presence
      of the neutral letters. We separated the effects of load and dilution by
      introducing dilution displays. They contained as many letters as the high-load
      displays but were clearly distinguished from the target, thus allowing for a low
      load processing mode. Distractor interference obtained under both the low-load
      and high-load conditions disappeared under the dilution condition. Hence, the
      display size effect traditionally misattributed to perceptual load is fully
      accounted for by dilution. Furthermore, when dilution is controlled for, it is
      high load not low load producing greater interference.

PMID- 20822301
TI  - The sparing is far from spurious: reevaluating within-trial contingency effects
      in the attentional blink.
AB  - The attentional blink is the marked deficit in awareness of a 2nd target (T2)
      when it is presented shortly after the 1st target (T1) in a stream of
      distractors. When the distractors between T1 and T2 are replaced by even more
      targets, the attentional blink is reduced or absent, indicating that the
      attentional blink results from online selection mechanisms that act in response
      to distracting input rather than being the result of T1-induced cognitive
      resource depletion. However, Dell'Acqua, Jolicoeur, Luria, and Pluchino (2009)
      recently contended that an attentional blink is found in the multiple-target case
      as long as the appropriate trial context and analyses are used, thus reinstating
      resource-based explanations of the attentional blink and challenging the
      selection account. Specifically, an attentional blink reemerges when target
      performance is analyzed contingent on previous target accuracy. We argue on
      theoretical and empirical grounds that neither the trial context nor the type of
      analysis poses a serious problem for selection accounts. We show that the
      attentional blink and previous target contingency effects can be dissociated,
      with the latter depending more on low-level, short-range competition. We conclude
      that selection mechanisms involved in filtering for targets still provide a
      strong and coherent explanation of the attentional blink.

PMID- 20822302
TI  - An alternative to the computational Speech Intelligibility Index estimates:
      direct measurement of rectangular passband intelligibilities.
AB  - The need for determining the relative intelligibility of passbands spanning the
      speech spectrum has been addressed by publications of the American National
      Standards Institute (ANSI). When the Articulation Index (AI) standard (ANSI,
      S3.5, 1969, R1986) was developed, available filters confounded passband and slope
      contributions. The AI procedure and its updated successor, the Speech
      Intelligibility Index (SII) standard (ANSI, S3.5, 1997, R2007), cancel slope
      contributions by using intelligibility scores for partially masked highpass and
      lowpass speech to calculate passband importance values; these values can be
      converted to passband intelligibility predictions using transfer functions.
      However, by using very high-order digital filtering, it is now possible to
      eliminate contributions from filter skirts and produce rectangular passbands.
      Employing the same commercial recording and the same one-octave passbands
      published in the SII standard (Table B.3), the present study compares Rectangular
      Passband Intelligibility (RPI) with SII estimates of intelligibility. The
      directly measured RPI differs from the computational SII predictions. Advantages
      resulting from direct measurement are discussed.

PMID- 20822303
TI  - Loudness change in response to dynamic acoustic intensity.
AB  - Three experiments investigate psychological, methodological, and domain-specific
      characteristics of loudness change in response to sounds that continuously
      increase in intensity (up-ramps), relative to sounds that decrease (down-ramps).
      Timbre (vowel, violin), layer (monotone, chord), and duration (1.8 s, 3.6 s) were
      manipulated in Experiment 1. Participants judged global loudness change between
      pairs of spectrally identical up-ramps and down-ramps. It was hypothesized that
      loudness change is overestimated in up-ramps, relative to down-ramps, using
      simple speech and musical stimuli. The hypothesis was supported and the
      proportion of up-ramp overestimation increased with stimulus duration. Experiment
      2 investigated recency and a bias for end-levels by presenting paired dynamic
      stimuli with equivalent end-levels and steady-state controls. Experiment 3 used
      single stimulus presentations, removing artifacts associated with paired stimuli.
      Perceptual overestimation of loudness change is influenced by (1) intensity
      region of the dynamic stimulus; (2) differences in stimulus end-level; (3) order
      in which paired items are presented; and (4) duration of each item. When
      methodological artifacts are controlled, overestimation of loudness change in
      response to up-ramps remains. The relative influence of cognitive and sensory
      mechanisms is discussed.

PMID- 20822304
TI  - Long-term semantic priming of word meaning.
AB  - Three experiments investigated facilitation in synonym decisions as a function of
      prior synonym decision trials that were either identical or semantically related.
      Experiment 1 demonstrated that semantically related prime trials produced less
      facilitation than identical prime trials, but facilitation from both persisted
      over 14 intervening trials. Experiments 2 and 3 demonstrated that word meaning
      retrieval without meaning comparison in prime trials was sufficient for
      persistent facilitation in semantically related targets, and meaning comparison
      was necessary for repetition priming to show greater facilitation than semantic
      priming. Results suggest that semantic priming in this task may solely reflect
      strength changes in abstract semantic representations, whereas repetition priming
      may reflect additional nondeclarative memory for operations performed in prime
      events.

PMID- 20822305
TI  - Attention is required for acquisition but not expression of new response biases.
AB  - Throughout a lifetime of interaction with the physical environment, people
      develop a strong bias to respond on the same side as the location of a target
      object, even when its location is irrelevant to the task at hand. Recent research
      has shown that this compatibility bias can be overridden with relatively brief
      but focused training. To better understand how such training affects preexisting
      response biases, we investigated whether attention is required to acquire and
      express a new bias to respond on the opposite side, thus creating an
      incompatibility bias. Participants practiced making responses on the opposite
      side from left and right tones and then made responses based on the frequencies
      (high or low) of the same tones. As in previous research, practice with a
      spatially incompatible mapping eliminated the compatible bias in the Simon task.
      The addition of an attention load (continuous secondary tracking task) during
      practice prevented learning the new response bias. However, once the new bias was
      learned, it overrode the compatibility bias regardless of available attentional
      resources. We suggest that not only can a quickly learned response bias overwhelm
      preexisting biases that are acquired over years of experience but that recently
      learned and older, preexisting biases are similarly affected by attention load.

PMID- 20822306
TI  - Metacognitive control and spaced practice: clarifying what people do and why.
AB  - What do learners do when they control whether to engage in massed or spaced
      practice? According to theories by Son (2004) and by Metcalfe and Kornell (2005),
      the tendency for learners to choose spaced practice over massed practice should
      decline as item difficulty becomes greater. Support originally was obtained when
      pairs containing unfamiliar words were presented briefly for study, but
      subsequent research has suggested that, under these conditions, learners had
      difficulty initially encoding the members of the to-be-learned pairs. In
      Experiments 1 and 2, we failed to support the previously mentioned prediction in
      conditions in which the difficulty of learning was not correlated with the
      difficulty of initially encoding the pair members. Learners' relative preference
      for spaced practice increased, rather than decreased, with greater item
      difficulty, consistent with either a discrepancy-reduction-like account or an
      agenda-based-regulation account. In Experiment 3, we independently varied item
      difficulty and the point value that items were worth on the final test. Learners'
      relative preference for spaced practice was greater for high- than for low-value
      items but was unaffected by item difficulty. These results are more consistent
      with an agenda-based-regulation account than with a discrepancy-reduction
      account. More generally, learners' choices appear to be strategic and to reflect
      theory-based decisions, suggesting some level of appreciation for the relative
      benefits of massed versus spaced practice.

PMID- 20822307
TI  - Molecular characteristics of the human pandemic influenza A virus (H1N1).
AB  - The outbreak of the human pandemic influenza A (H1N1) has caused a considerable
      public concern. The aim of this review was to improve our understanding of this
      novel virus by analyzing the relationships between its molecular characteristics
      and pathogenic properties. Results of this analysis indicate that the human
      pandemic influenza A (H1N1) virus is a new re-assorted virus, which combines
      genetic materials from the avian flu (H1N1) virus, classical swine flu (H1N1)
      virus, human flu (H3N2) virus, and Eurasian swine flu (H1N1) virus. Analysis of
      the sequences for receptor-binding and cleavage sites of hemagglutinin (HA),
      stalk region of neuraminidase (NA), non-structural protein 1 (NS1), polymerase
      basic protein 2 (PB2), and polymerase basic protein 1 (PB1) suggested that (i)
      the human pandemic influenza A (H1N1) virus is a low virulent and low pathogenic
      virus, (ii) its replication is restricted to the cells of upper respiratory
      tract, so it does not lead to a systemic infection, (iii) it spreads among humans
      only, (iv) its replication could be inhibited by oseltamivir, zanamivir,
      interferon (IFN), and tumor necrosis factor alpha (TNF-alpha). A potential
      application of amantadine might be complicated by the drug-resistant virus
      strains.

PMID- 20822308
TI  - Molecular characterization of long terminal repeat of porcine endogenous
      retroviruses in Chinese pigs.
AB  - Pigs offer an unlimited source of xenografts for humans. However, vertically
      transmitted Porcine endogenous retrovirus (PERV) poses an infectious risk in the
      course of pig-to-human transplantation. In this study, we characterized PERV long
      terminal repeat (LTR) sequences from three species of Chinese pigs Banna minipig
      inbred (BMI), Wu-Zhi-Shan pig (WZSP), and Neijiang pig (NJP-A), and compared them
      with those of known PERVs (PERV-A, PERV-B, PERV-C, PERV-NIH, and 293-PERV-43).
      Genomic DNA extracted from peripheral blood mononuclear cells (PBMCs) of the
      Chinese pigs was used for PCR-amplification, cloning, and sequencing of LTRs. The
      sequences of BMI and WZSP LTRs were found identical with those of PERV-A and PERV
      B, while that of NJP-A LTR was found close to those of PERV-C and PERV-NIH. The
      gammaretroviral nature of PERV LTRs from Chinese pigs was proved. These LTRs
      contained also promoter elements including enhancer-like repeats comparable with
      those of other PERVs. These findings suggested that PERVs from Chinese pigs were
      similar to PERV-A and PRV-B. Moreover, this study provided new data for the
      evaluation and selection of pigs to be used in the xenotransplantation.

PMID- 20822309
TI  - Characterization of antigens for Q fever serodiagnostics.
AB  - The aim of this study was to identify candidate proteins for serodiagnostics of Q
      fever by monoclonal antibodies (MAbs), and to clone, express, and purify the
      selected proteins for use as antigens in ELISA. The reactivity of three MAbs to
      Coxiella burnetii (C. b.) Nine Mile strain and one MAb to Priscilla strain was
      tested using SDS-PAGE, 2-D gel electrophoresis, immunoblot analysis, and mass
      spectrometry. Three immunoreactive Q fever-specific proteins discriminated by
      MAbs, namely the CBU_0937 protein, outer membrane Com1 (CBU_1910) protein, and
      elongation factor Tu (CBU_0236) were identified. Successful PCR-amplification,
      cloning, expression, and purification of the recombinant proteins Com1 and
      CBU_0937 allowed their use for the screening of sera from patients with Q fever
      endocarditis (18) or acute Q fever (16) in ELISA. The recombinant protein
      CBU_0937 with unknown biological function proved to be a more applicable
      diagnostic tool for Q fever ELISA as compared to the Com1 protein.

PMID- 20822310
TI  - Glycosylation is not necessary for recognition of the fusion glycoprotein domain
      of the human respiratory syncytial virus by a polyclonal antibody.
AB  - Human respiratory syncytial virus (HRSV) is a leading pathogen causing lower
      respiratory tract infections in infants and young children worldwide. In line
      with the development of an effective vaccine against HRSV, a domain of the fusion
      (F) glycoprotein of HRSV was produced and its immunogenicity and antigenic
      properties, namely the effect of deficient glycosylation was examined. A His
      tagged recombinant F (rF) protein was expressed in Escherichia coli, solubilized
      with 8 mol/l urea, purified by the Ni-NTA affinity chromatography and used for
      the raising of a polyclonal antibody in rabbits. The non-glycosylated rF protein
      proved to be a strong immunogen that induced a polyclonal antibody that was able
      to recognize also the glycosylated F1 subunit of native HRSV. The other way
      around, a polyclonal antibody prepared against the native HRSV was able to react
      with the rF protein. These results indicated that glycosylation was not necessary
      for the F domain aa 212-574 in order to be recognized by the specific polyclonal
      antibody.

PMID- 20822311
TI  - Study of a chimeric foot-and-mouth disease virus DNA vaccine containing
      structural genes of serotype O in a genome backbone of serotype Asia 1 in guinea
      pigs.
AB  - Since foot-and-mouth disease virus (FMDV) serotypes display a great genetic and
      antigenic diversity, there is a constant requirement to monitor the performance
      of FMDV vaccines in the field with respect to their antigenic coverage. To avoid
      possible antigenic changes in field FMDV isolates during their adaptation to BHK
      21 cells, a standard step used in production of conventional FMDV vaccines, the
      custom-made chimeric conventional or DNA vaccines, in which antigenic
      determinants are replaced with those of appropriate field strains, should be
      constructed. Using this approach, we made a plasmid-based chimeric FMDV DNA
      vaccine containing structural genes of serotype O in the genome backbone of
      serotype Asia 1, all under the control of Human cytomegalovirus (HCMV) immediate
      early gene promoter. BHK-21 cells transfected with the chimeric DNA vaccine did
      not show cytopathic effect (CPE), but expressed virus-specific proteins as
      demonstrated by 35S-methionine labeling and immunoprecipitation. Guinea pigs
      immunized with the chimeric DNA vaccine produced virus-specific antibodies
      assayed by ELISA and virus neutralization test (VNT), respectively. The chimeric
      DNA vaccine showed a partial protection of guinea pigs challenged with the
      virulent FMDV. Although the chimeric DNA vaccine, in general, was not as
      effective as a conventional one, this study encourages further work towards the
      development of genetically engineered custom-made chimeric vaccines against FMDV.

PMID- 20822312
TI  - Human immunodeficiency virus 1 Vpu protein does not affect the conversion of
      influenza A virus hemagglutinin to its low-pH conformation in an acidic trans
      Golgi compartment.
AB  - The 81-aa Vpu protein of Human immunodeficiency virus 1 (HIV-1) is a structural
      analogue of the M2 protein of influenza A virus (IAV). Expression of Vpu in
      Xenopus oocytes has showed that it can form a voltage-activated ion channel
      permeable to Na+ and K+ ions (Ewart et al., 1996). To investigate whether Vpu has
      a pH-modulating activity comparable to that of M2, Vpu was co-expressed with the
      pH-sensitive hemagglutinin (HA) from IAV. The results indicated that Vpu was
      unable to reduce the acidity of the exocytic pathway and reduce the conversion of
      the pH-sensitive HA to its low-pH conformation during transport to the cell
      surface. Despite these findings, we did not exclude the possibility that Vpu
      formed a weak ion channel with almost pore-like characteristics as was recently
      suggested.

PMID- 20822313
TI  - Sequence and phylogenetic analyses of neuraminidase gene of Iranian seasonal
      influenza H1N1 viruses from 2005-2009 and corresponding vaccine strains.
AB  - Prophylaxis of influenza A virus infections is based on the vaccines inducing
      antibodies to the major viral antigens, hemagglutinin (HA) and neuraminidase
      (NA). Since these antigens continuously change during virus replication in
      various hosts, only the currently circulating strains should be used in the
      vaccines. Besides, monitoring of the naturally occurring changes in HA, NA, and
      respective genes, especially those associated with resistance to the NA
      inhibitors is necessary. The NA genes of 30 Iranian isolates of influenza H1N1
      virus from the seasons 2005-2009 were sequenced and subjected to the sequence and
      phylogenetic analyses. The seasonal isolates turned out to be closely related to
      the corresponding vaccine strains, except for the 2007-2008 isolates, which also
      displayed a higher nucleotide variation. A resistance to the NA inhibitors was
      found in the 2008-2009 isolates only. The average nucleotide identities of the
      isolates with corresponding vaccine strains for the years 2005-2009 were 98.83%,
      98.55%, 98.7%, 97.55%, and 98.76%, respectively.

PMID- 20822314
TI  - Identification of target cells for Goose parvovirus infection in the immune
      system organs.
AB  - Target cells for Goose parvovirus (GPV) in natural infection are still unknown.
      In this study, immune system organs namely the spleen, bone marrow, thymus, bursa
      of Fabricius, and blood of experimentally GPV-infected goslings were examined by
      an immunoassay and flow cytometry for the presence of viral antigen and by a PCR
      for viral genome. The results indicated that the virus replicated in some cells
      of the spleen and bone marrow, but not in peripheral blood lymphocytes (PBLs).
      These data suggested that some cell populations in the spleen and bone marrow
      were targets for GPV infection. In addition, the immunoassay used for the
      detection of GPV was found comparable with a PCR in reliability and sensitivity.

PMID- 20822315
TI  - La France disease of the cultivated mushroom Agaricus bisporus in Poland.
AB  - Presence of the virus associated with La France disease was confirmed in the
      mushrooms collected from different farms located in Western Poland. Double
      stranded RNA (dsRNA) was isolated from the mushrooms exhibiting a wide range of
      the disease symptoms including premature veil opening, brown-colored mushrooms,
      and loss of crop yield. The presence of dsRNA molecules (M1, M2, and L3) was
      confirmed by RT-PCR and sequencing. Furthermore, La France isometric virus (LFIV)
      like particles were observed in the mushrooms extracts in electron microscopy.
      The LFIV infection was found in 120 of 200 mushroom samples tested. The amount of
      the infected samples indicated the high occurrence of La France disease that
      could be a threat to the mushroom industry in Poland.

PMID- 20822316
TI  - Development of a probe-based blotting technique for the detection of tobacco
      streak virus.
AB  - Digoxigenin (DIG)-labeled DNA probe was developed for a sensitive and rapid
      detection of the tobacco streak virus (TSV) isolates in India by dot-blot and
      tissue print hybridization techniques. DIG-labeled DNA probe complementary to the
      coat protein (CP) region of TSV sunflower isolate was designed and used to detect
      the TSV presence at field levels. Dot-blot hybridization was used to check a
      large number of TSV isolates with a single probe. In addition, a sensitivity of
      the technique was examined with the different sample extraction methods. Another
      technique, the tissue blot hybridization offered a simple, reliable procedure and
      did not require a sample processing. Thus, both non-radioactively labeled probe
      techniques could facilitate the sample screening during TSV outbreaks and offer
      an advantage in quarantine services.

PMID- 20822317
TI  - Molecular characterization of Ramie mosaic virus isolates detected in Jiangsu and
      Zhejiang provinces, China.
AB  - Virus isolates were obtained from three ramie samples (Boehmeria nivea L.)
      showing yellow mosaic symptoms collected in Jiangsu and Zhejiang provinces,
      China. Comparison of partial DNA-A fragments amplified with begomovirus universal
      primers PA/PB revealed that these viral isolates shared a high sequence identity.
      The complete DNA-A sequences of two isolates J4 and Z1 were determined to be 2736
      and 2737 nts, respectively, sharing 94.7% nucleotide sequence identity with each
      other. Also, the DNA-B components were identified for J4 and Z1 isolates and
      comprised 2717 and 2719 nts, respectively, sharing 88.6% nucleotide sequence
      identity with each other. Furthermore, sequence alignment and phylogenetic
      analysis showed that J4 and Z1 isolates had the highest sequence identities (93.6
      94.7%) with isolates of Ramie mosaic virus (RamMV) for DNA-A. These molecular
      data suggested that J4 and Z1 may be two different isolates of RamMV. This is the
      first report about the occurrence of a bipartite begomovirus in these regions of
      China.

PMID- 20822318
TI  - ATLA - a truly international journal.

PMID- 20822319
TI  - FRAME and the three Rs: yesterday, today and tomorrow.

PMID- 20822320
TI  - A comparative evaluation of in vitro skin sensitisation tests: the human cell
      line activation test (h-CLAT) versus the local lymph node assay (LLNA).
AB  - We previously developed the human cell-line activation test (h-CLAT) in vitro
      skin sensitisation test, based on our reported finding that a 24-hour exposure of
      THP-1 cells (a human monocytic leukaemia cell line) to sensitisers is sufficient
      to induce the augmented expression of CD86 and CD54. The aim of this study is to
      confirm the predictive value of h-CLAT for skin sensitisation activity by
      employing a larger number of test chemicals. One hundred chemicals were selected,
      according to their categorisation in the local lymph node assay (LLNA), as being:
      extreme, strong, moderate and weak sensitisers, and non-sensitisers. The
      correlation of the h-CLAT results with the LLNA results was 84%. There were some
      false negatives (e.g. benzoyl peroxide, hexyl cinnamic aldehyde) and some false
      positives (e.g. 1-bromobutane, diethylphthalate). Eight out of the 9 false
      negatives (89%) were water-insoluble chemicals. The h-CLAT could positively
      predict not only extreme and strong sensitisers, but also moderate and weak
      sensitisers, though the detection rates of weak sensitisers and non-sensitisers
      were comparatively low. Some sensitisers enhanced both CD86 and CD54 levels, and
      some enhanced the level of only one of them. The use of the combination of CD86
      and CD54 induction as a positive indicator, improved the accuracy of the test. In
      conclusion, the h-CLAT is expected to be a useful cell-based in vitro method for
      predicting skin sensitisation potential.

PMID- 20822321
TI  - The Pharmaceutical Aerosol Deposition Device on Cell Cultures (PADDOCC) in vitro
      system: design and experimental protocol.
AB  - The development of aerosol medicines typically involves numerous tests on
      animals, due to the lack of adequate in vitro models. A new in vitro method for
      testing pharmaceutical aerosol formulations on cell cultures was developed,
      consisting of an aerosolisation unit fitting a commercial dry powder inhaler
      (HandiHaler(c), Boehringer Ingelheim, Germany), an air-flow control unit
      (Akita(c), Activaero, Germany) and a custom-made sedimentation chamber. This
      chamber holds three Snapwell(c) inserts with monolayers of pulmonary epithelial
      cells. The whole set-up, referred to as the Pharmaceutical Aerosol Deposition
      Device On Cell Cultures (PADDOCC) system, aims to mimic the complete process of
      aerosol drug delivery, encompassing aerosol generation, aerosol deposition onto
      pulmonary epithelial cells and subsequent drug transport across this biological
      barrier, to facilitate the investigation of new aerosol formulations in the early
      stages of development. We describe here, the development of the design and the
      protocol for this device. By testing aerosol formulations of budesonide and
      salbutamol sulphate, respectively, reproducible deposition of aerosol particles
      on, and the integrity of, the pulmonary cell monolayer could be demonstrated.

PMID- 20822322
TI  - E-SovTox: An online database of the main publicly-available sources of toxicity
      data concerning REACH-relevant chemicals published in the Russian language.
AB  - A new open-access online database, E-SovTox, is presented. E-SovTox provides
      toxicological data for substances relevant to the EU Registration, Evaluation,
      Authorisation and Restriction of Chemicals (REACH) system, from publicly
      available Russian language data sources. The database contains information
      selected mainly from scientific journals published during the Soviet Union era.
      The main information source for this database - the journal, Gigiena Truda i
      Professional'nye Zabolevania [Industrial Hygiene and Occupational Diseases],
      published between 1957 and 1992 - features acute, but also chronic, toxicity data
      for numerous industrial chemicals, e.g. for rats, mice, guinea-pigs and rabbits.
      The main goal of the abovementioned toxicity studies was to derive the maximum
      allowable concentration limits for industrial chemicals in the occupational
      health settings of the former Soviet Union. Thus, articles featured in the
      database include mostly data on LD50 values, skin and eye irritation, skin
      sensitisation and cumulative properties. Currently, the E-SovTox database
      contains toxicity data selected from more than 500 papers covering more than 600
      chemicals. The user is provided with the main toxicity information, as well as
      abstracts of these papers in Russian and in English (given as provided in the
      original publication). The search engine allows cross-searching of the database
      by the name or CAS number of the compound, and the author of the paper. The E
      SovTox database can be used as a decision-support tool by researchers and
      regulators for the hazard assessment of chemical substances.

PMID- 20822323
TI  - Combined in vitro tests as an alternative to in vivo eye irritation tests.
AB  - Accurate methods that test the eye irritation potential of chemicals, which do
      not involve the use of animals, are needed to meet new regulatory standards. We
      evaluated the applicability and predictive capacity of five in vitro tests for
      eye irritation: the Hen's Egg Test-Chorioallantoic Membrane (HET-CAM) assay; the
      Chorioallantoic Membrane-Trypan Blue Staining (CAM-TBS) assay; the Fluorescein
      Leakage Test (FLT); the 3T3-Neutral Red Uptake (3T3-NRU) cytotoxicity assay; and
      the red blood cell (RBC) haemolysis assay. A panel of 16 chemicals (some at
      multiple concentrations) was assessed by using the five tests, and the results
      were compared with historical in vivo Draize test data. The results showed rank
      correlation and class concordance between the five alternative methods and the
      Draize test for the 16 chemicals. These in vitro assays had good predictive
      capacity, reproducibility and reliability when compared to the Draize test. The
      best relationship was between the HET-CAM, CAM-TBS and FLT results, and the
      modified maximum average score(s) (MMAS). A prediction model (PM) was developed,
      based on the maximum possible correlation between the MMAS and the HET-CAM, CAM
      TBS and FLT results. The PM had a good predictive capacity when compared to the
      results of animal tests, indicating its potential value for the in vitro
      screening of chemicals for eye irritation effects.

PMID- 20822324
TI  - The current scientific and legal status of alternative methods to the LD50 test
      for botulinum neurotoxin potency testing. The report and recommendations of a
      ZEBET Expert Meeting.

PMID- 20822325
TI  - Introducing ethical evaluation of the use of animals in experiments in the Near
      East.
AB  - Turkey and Iran are two Near East countries that are developing ethical
      regulation systems for animal experiments, following significant developments in
      this field in neighbouring Europe. In Turkey, legislation was passed between 2004
      and 2006 to mandate ethical review of experiments which involve the use of
      laboratory animals. Today, one central and 73 local ethics committees exist, to
      evaluate the use of animals and the numbers of animals used, and to consider
      applications for animal experimentation. In Iran, Animal Ethics Committees (AECs)
      were established in 2004 in approximately 50 medical universities. The objective
      of the AECs is to preserve animal welfare and ethics, taking into account Islamic
      principles, and to be cognisant of world trends for the improvement of laboratory
      animal welfare. The recent establishment of animal ethical review in the Near
      East could benefit from experiences in Western countries, in their evolution
      toward high standards of experimental animal ethics.

PMID- 20822327
TI  - Biomarkers of inflammation and placental dysfunction are associated with
      subsequent preterm birth.
AB  - OBJECTIVE: To assess whether the analysis of high sensitivity C-Reactive Protein
      (hsCRP), a biomarker of inflammation, and placental growth factor (PlGF), a
      biomarker of placental dysfunction, could help identify patients at risk for
      preterm birth (PTB). METHODS: We performed a prospective cohort study of women
      with symptoms of preterm labor (22-33 6/7 weeks). Maternal serum was analyzed for
      hsCRP and PlGF. Median biomarker values were used as analytic cut-points. We
      performed chi-square tests of association between biomarkers and PTB,
      nonparametric tests to compare medians, and logistic regression to determine the
      odds of PTB associated with biomarker values. Test characteristics of each
      biomarker were calculated. RESULTS: 56.3% of the cohort (N = 96) delivered
      preterm. Median hsCRP (N = 78) was 4.34 mg/L, and median PlGF (N = 86) was 558.25
      mg/l. In the setting of inflammation (high hsCRP), women with low PlGF had a 6.84
      fold (95%CI: 1.57-29.80) increased risk of PTB. In the setting of placental
      dysfunction (low PlGF), women with high hsCRP had a 5.97-fold (95%CI: 1.52-23.43)
      increased risk of PTB. CONCLUSIONS: Our results suggest an interplay between
      inflammation and placental dysfunction in the pathogenesis of PTB. Analyzing
      biomarkers that reflect different pathways of PTB may hold promise for
      identifying patients at greatest risk.

PMID- 20822326
TI  - Antipyretic and antinociceptive effects of Nauclea latifolia root decoction and
      possible mechanisms of action.
AB  - CONTEXT:  Nauclea latifolia Smith (Rubiaceae) is a small tree found in tropical
      areas in Africa. It is used in traditional medicine to treat malaria, epilepsy,
      anxiety, pain, fever, etc. OBJECTIVE:  The aim of this study was to investigate
      the effects of Nauclea latifolia roots decoction on the peripheral and central
      nervous systems and its possible mechanisms of action. MATERIALS AND METHODS: 
      The analgesic investigation was carried out against acetic acid-induced writhing,
      formalin-induced pain, hot-plate and tail immersion tests. The antipyretic
      activity was studied in Brewer's yeast-induced pyrexia in mice. Rota-rod test and
      bicuculline-induced hyperactivity were used for the assessment of locomotor
      activity. RESULTS:  Nauclea latifolia induced hypothermia and had antipyretic
      effects in mice. The plant decoction produced significant antinociceptive
      activity in all analgesia animal models used. The antinociceptive effect
      exhibited by the decoction in the formalin test was reversed by the systemic
      administration of naloxone, N(omega)-L-nitro-arginine methyl ester or
      glibenclamide. In contrast, theophylline did not reverse this effect. Nauclea
      latifolia (antinociceptive doses) did not exhibit a significant effect on motor
      coordination of the mice in Rota-rod performance. Nauclea latifolia protected
      mice against bicuculline-induced behavioral excitation. DISCUSSION AND
      CONCLUSION:  Overall, these results demonstrate that the central and peripheral
      effects of Nauclea latifolia root decoction might partially or wholly be due to
      the stimulation of peripheric opioid receptors through the action of the nitric
      oxide/cyclic monophosphate guanosin/triphosphate adenosine (NO/cGMP/ATP)
      sensitive- K(+) channel pathway and/or facilitation of the GABAergic
      transmission.

PMID- 20822328
TI  - Biochemical markers of neonatal myocardial dysfunction.
AB  - INTRODUCTION: Cardiac ultrasounds (US) are not always available at the bedside.
      Cardiac Troponin I (cTnI), CK-MB and NT-proBNP may be an alternative or
      complementary to influence evaluation and treatment. OBJECTIVES: To determine
      reference ranges of biochemical markers cTnI, CK-MB and NT-proBNP in normal
      neonates. METHODOLOGY: Cord and blood samples were collected from neonates and
      the above biochemical markers were determined. Ultrasounds were performed
      blindly. RESULTS: CK-MB remains constant from cord blood to the first day,
      declining thereafter to almost half the values (81.5 vs 52.0 U/l); cTnI increases
      from 0.004 to 0.058 ng/ml by 72 h falling to 0.030 by day 10; NT-proBNP peaks by
      24 h (5085.5 pg/ml), subsiding to 3388.5 pg/ml by day 3, falling to 1316.0 pg/ml
      by day 10. CONCLUSIONS: CK-MB, mostly of muscle origin and reflecting labor
      stress or injury, is not to recommend as a measure of myocardial damage in the
      neonate. The rise in cTnI may be explained by a degree of myocardial involvement,
      albeit physiological. The initial rise and subsequent fall of NT-proBNP
      represents the physiological ventricular overload of transient birth adaptation.

PMID- 20822329
TI  - Fetal alloimmune thrombocytopenia: is less invasive antenatal management safe?
AB  - OBJECTIVES: The aim of this study was to review recent multicenter data on
      antenatal management of anti-HPA-1a fetal alloimmune thrombocytopenia and, based
      on this retrospective study and on recent literature, to evaluate if FBS modified
      the obstetrical management. MATERIAL AND METHODS: This retrospective study in
      France includes 23 pregnancies in 21 women who had a previous thrombocytopenic
      infant due to anti HPA-1a alloimmunization. All pregnant women received
      intravenous immunoglobulin (IVIG) treatment, with or without corticosteroids.
      Fetal blood sampling (FBS) was performed before any therapy (four cases) or
      during pregnancy (nine cases). RESULTS: Infants whose mother received treatment
      had a significantly higher neonatal platelet count than the corresponding sibling
      (p = 0.003). In eight cases, therapy was started late during pregnancy. In three
      cases, treatment was discontinued 3 or 4 weeks before birth, and this was
      associated with a poorer result. No in utero intracranial hemorrhage was recorded
      in the infants for whom maternal therapy continued to term. Adverse effects were
      not observed in any case. All babies were delivered by cesarean even when FBS was
      performed. One emergency cesarean was performed for fetal bradycardia after FBS.
      CONCLUSION: This study confirmed that maternal therapy with intravenous
      immunoglobulin for fetal alloimmune thrombocytopenia gives satisfactory results.
      It also showed that a less invasive approach, especially a reduction in the
      number of fetal blood samples, is possible without deleterious consequences. This
      observation suggests also to start IVIG early during pregnancy and to continue
      treatment up to delivery.

PMID- 20822330
TI  - The significance of -786T > C polymorphism of endothelial NO synthase (eNOS) gene
      in severe preeclampsia.
AB  - OBJECTIVE: Preeclampsia (PE) is believed to be induced by endothelial cell
      dysfunction in placenta. Highly polymorphic endothelial nitric oxide synthase
      (eNOS) activity belongs to the factors significantly influencing vaso-motor tone
      in placenta and PE susceptibility. The aim of this study was to evaluate
      prevalence of -786T/C polymorphism of eNOS gene in the groups of women with mild
      and severe PE. STUDY DESIGN: The study was performed in the group of 218
      preeclamptic (including 136 with severe PE) and of 400 normotensive healthy women
      delivered normally after a healthy gestation. The eNOS -786T/C polymorphism was
      determined using PCR/RFLP assay. Additionally, detailed correlation between eNOS
      genotypes and clinical/laboratory data in the PE group has been analyzed.
      RESULTS: The higher frequency of mutated homozygous CC genotypes (17.4% vs. 11.5%
      in controls, OR 1.62, n.s.) and of C alleles (allelic frequency 44.1 vs. 36.6%;
      OR 1.36, p = 0.012) in the group of PE has been determined. Furthermore, in the
      group of severe PE the overrepresentation of mutated CC genotypes (23.5% vs.
      11.5%, OR 2.37, p = 0.0014) and mutated C alleles (47.8 vs. 36.6%, OR 1.58, p =
      0.0016) has been found. CONCLUSIONS: The presence of mutated homozygous CC
      genotype and C allele of -786T/C polymorphism of eNOS gene influences the higher
      susceptibility to develop severe PE development.

PMID- 20822331
TI  - Early origin of adult renal disease.
AB  - Observational studies in humans and experimental studies in animals have clearly
      shown that renal failure may start early in life. 'Fetal programming' is
      regulated by adaptations occurring in uterus including maternal nutrition,
      placental blood supply, and epigenetic changes. Low birth weight predisposes to
      hypertension and renal insufficiency. Congenital abnormalities of the kidney and
      urinary tract, adverse postnatal events, wrong nutritional habits may produce
      renal damage that will become clinically relevant in adulthood. Prevention should
      start early in children at risk of renal disease.

PMID- 20822332
TI  - Neonatal outcomes in a population of late-preterm infants.
AB  - The late-preterm infants are a group of premature steadily increasing, different
      from term infants as immature in terms of respiratory, metabolic, neurological,
      and immunological features. They may present at birth and during the first week
      of life various diseases and brain lesions echographically evident. We analyzed
      the neonatal outcomes of 417 late-preterm infants, born in our Department of
      Neonatology in a period of two and a half years, evaluating respiratory problems
      (RDS, transient tachypnea, pneumonia, pneumothorax, and apnea), metabolic
      problems (hypoglycemia, hypomagnesemia, hypo-hypernatremia, dehydration,
      hypocalcemia, and hyperbilirubinemia), infections, neurological symptoms
      associated with electrolyte disturbances, the disease patterns observed by
      ultrasound examination of the brain, the kidney ultrasound images, genital
      malformations.

PMID- 20822333
TI  - The strange destiny of Caterina de' Medici and a case of puerperal fever in the
      sixteenth century.
AB  - The aim of this study is the reconstruction of a case of puerperal fever, which
      affected the mother of Caterina de' Medici, the future Queen of France, in 1519.
      Only unpublished data found in the Archives were used, to follow the onset and
      the development of the disease, offering a glimpse into medical perception of the
      time. The description of the case provides interesting points of contact with
      modern medicine.

PMID- 20822334
TI  - Polymorphisms of plasminogen activator inhibitor-1, angiotensin converting enzyme
      and coagulation factor XIII genes in patients with recurrent spontaneous
      abortion.
AB  - We investigated polymorphisms of plasminogen activator inhibitor-1 (PAI-1),
      angiotensin converting enzyme (ACE ) and coagulation factor XIII (FXIII) genes
      and their association with recurrent spontaneous abortion (RSA) in Iranian
      patients and normal healthy controls. Ten (18.5%) patients were homozygote
      (4G/4G) for PAI-1 polymorphism, in contrast with two (2%) controls (p = 0.001).
      Patients with homozygote 4G mutation were significantly more prone to RSA in
      contrast to others (odds ratio: 11.0, 95% CI: 2.3-52.4). Nineteen (30.2%)
      patients and 25 (26.6%) controls were homozygote (DD) for ACE polymorphism. We
      observed only two patients and one control with homozygosity (34leu) for FXIII
      polymorphism. 4G/4G polymorphism for PAI-1 gene could be a thrombophilic mutation
      leading to abortion in Iranian population.

PMID- 20822335
TI  - Shared decision-making in neonatology: an utopia or an attainable goal?
AB  - Medical decision making is sometimes considered as a relatively simple process in
      which a decision may be made by the physician, by the patient, or by both patient
      and physician working together. There are three main models of decision making-
      paternalism, patient informed choice, and shared decision-making (SDM), having
      each one of these drawbacks and limitations. Historically, the most adopted one
      was the paternalism (strongly 'Doctor knows best'), where the professional made
      the decision based on what he/she considered to be as the patient's best
      interest, not necessarily contemplating patient's will and wishes. Currently, at
      the antipodes, the patient informed choice, where the patient makes his/her
      decision based on information received from the physician with no possible
      interference of professional's own preferences, seems to be the preferred
      relationship standard. SDM represents an intermediate approach between the two
      above-mentioned opposite models, being a medical process that involves actively
      the doctor and the patient who both bring their own facts and preferences to
      reach an agreement on the decision on if, when and how to treat a disease. This
      model, being characterized by elements pertaining to both the others, is gaining
      popularity in several medical and surgical scenarios whenever a competent patient
      is able to actively participate into the decisional process. On this basis can
      this model be implemented also in a Neonatology Intensive Care Unit where little
      patients are--by nature--incompetent, being the diagnostic/therapeutic choices
      taken by parents? We focused on this complex item considering four possible
      different scenarios and it seems to us that it could be possible to introduce
      such an approach, providing that parents' empowerment, a good physician's
      communication skill and consideration of all cultural, religious, economic, and
      ethic values of every single actor have been fairly taken into account.

PMID- 20822336
TI  - Personalized neonatal medicine.

PMID- 20822337
TI  - Decreased VASP phosphorylation in platelets of male and female smokers of young
      age.
AB  - Cigarette smoking represents a major risk factor for atherosclerosis as smoking
      delivers huge amounts of oxidants and toxins to the human body and elicits an
      inflammatory response. Notably, oxidative stress and inflammation-derived
      oxidants are able to modulate platelet function. This is of particular interest
      as platelets and their activation state are implicated in the very early phases
      of the development of cardiovascular disease. We therefore investigated the
      impact of smoking on platelet reactivity and phosphorylation of vasodilator
      stimulated phosphoprotein (VASP) in a group of 20 young smokers (age 25.7 +/-
      4.36 years; 10 male/10 female) and an age- and gender-matched control group.
      After overnight smoking cessation, basal and prostaglandin E1-induced
      phosphorylation state of intraplatelet VASP was compared between smokers and non
      smokers. Furthermore, the ability of several concentrations of ADP to induce
      surface expression of P-selectin was assessed. Our results show that both the
      basal as well as prostaglandin E1-induced phosphorylation states of VASP are
      significantly decreased in the smokers group. These effects can be observed in
      both male and female smokers to a similar extent. Furthermore, we found
      significantly enhanced surface expression of P-selectin in response to different
      concentrations of ADP in smokers; these differences are even more pronounced in
      the presence of prostaglandin E1. As phosphorylated VASP represents a negative
      regulator of platelet activation, decreased VASP phosphorylation would be
      supposed to result in platelet hyperreactivity and pro-coagulant and pro
      inflammatory consequences. Therefore, our findings add another piece of evidence
      to the harmful effects of smoking in both male and female smokers.

PMID- 20822338
TI  - Wound healing activity of Withania coagulans in streptozotocin-induced diabetic
      rats.
AB  - CONTEXT: Withania coagulans Dunal. (Solanaceae) has been shown to possess
      hypoglycemic, free radical scavenging and wound healing activity. Therefore, it
      may be worthwhile to study the effect of Withania coagulans in diabetic wound
      healing. OBJECTIVE: This study included determination of rate of wound
      contraction and estimation of various biochemical parameters such as collagen,
      hexosamine, total protein, total DNA, SOD and CAT levels in the granulation
      tissues. MATERIALS AND METHODS: The hydroalcoholic fraction of the methanolic
      extract (standardized by withaferin-A using high performance thin layer
      chromatography (HPTLC) )of Withania coagulans in the form of 10% w/w ointment
      topically and at a dose of 500 mg/kg per oral (p.o.) was administered to
      streptozotocin-induced diabetic rats. The results obtained were compared with
      diabetic control and Aloe barbadensis Miller (syn. Aloe vera L.) (Liliaceae) was
      used as a reference drug. RESULTS: The amount of withaferin-A present in the
      methanolic extract was 3.67 mg/g of the extract. The hydroalcoholic fraction in
      both the forms, i.e., topical (10% w/w ointment) and oral (500 mg/kg, p.o.)
      showed a significant increase in the rate of wound contraction (83.02% topical
      and 65.14% oral) topical and 93.18% oral) when compared to diabetic control (66
      which was further justified with significant increase in the levels of collagen,
      protein, DNA, SOD, CAT, and decreased level of hexosamine. DISCUSSION AND
      CONCLUSION: The hydroalcoholic fraction of Withania coagulans in oral form is
      found to be more effective than the topical form. However, further studies are in
      progress to find the lead molecules responsible for the wound healing effect.

PMID- 20822339
TI  - Paradigm change in immune correlation: cellular or humoral?

PMID- 20822340
TI  - Bluetongue vaccination in Europe.

PMID- 20822342
TI  - Phase III HIV vaccine trial in Thailand: a step toward a protective vaccine for
      HIV.
AB  - The large human efficacy trail in Thailand, RV144, was concluded in the summer of
      2009. This is the first Phase III trial to show limited, but significant,
      efficacy in preventing HIV acquisition. This trial represents the first sign that
      a preventive vaccine for HIV may be feasible. The vaccine regimen tested in
      Thailand consisted of priming with a Canarypox vector carrying three synthetic
      HIV genes. The priming was followed by booster inoculations with two recombinant
      envelope proteins from HIV, clade B and E. The need to understand the role in
      protection from HIV acquisition of the new responses, induced by this vaccine
      combination, has brought together many researchers with the common goal of
      improving the development of a safe and effective vaccine for HIV.

PMID- 20822343
TI  - Current status of GV1001 and other telomerase vaccination strategies in the
      treatment of cancer.
AB  - GV1001 is a telomerase-specific, promiscuous class II peptide vaccine which is
      currently in an advanced stage of clinical development. This article reviews the
      biological rationale underpinning the design of ongoing studies with the vaccine
      as well as its immunogenicity and clinical activity. It places GV1001 in the
      context of other immunotherapeutic approaches targeting telomerase and assesses
      the chances of the vaccine becoming a future standard of care in the treatment of
      cancer.

PMID- 20822344
TI  - Current status of pneumococcal vaccines: lessons to be learned and new insights.
AB  - One of the great success stories in pneumococcal vaccines is the 7-valent
      conjugated pneumococcal vaccine (PCV-7); and with wider coverage, the broad
      prevention it offers would be possible with new vaccines. The 7th International
      Symposium on Pneumococci and Pneumococcal Diseases (ISPPD-7) was held on the 14
      18 March 2010 in Tel Aviv, Israel. During this symposium, clinical and
      epidemiological features in the post-PCV-7 era, current studies about two new
      approved PCVs (PHiD-CV and PCV-13) and new data about protein-based vaccines were
      extensively evaluated. Routine surveillance for pneumococcal infections is
      essential for all countries whether pneumococcal vaccines are available or not,
      and long-term results of surveillance help us to understand the PCVs potential
      benefits. Current epidemiological data about serotype 6C have also been presented
      from different countries and existing PCVs' efficacy against serotype 6C should
      be evaluated. In the post-PCV7 era, we have some new emerging serotypes and we
      also need new vaccines or interventions focused on protection for children
      against serotypes prevalent in the developing world or broad protection across
      all pneumococcal serotypes. Effectiveness of the new PCVs against nasopharyngeal
      carriage, acute otitis media and invasive infections need to be investigated in
      the real world; immunogenicity of investigational protein-based vaccines, are
      still evaluated in different settings. We will have a chance to hear and discuss
      all the new achievements in the many aspects related to pneumococcal diseases at
      the next ISPPD-8, which will be held in Iguacu Falls in 2012.

PMID- 20822345
TI  - Vaccines for all: Institut Pasteur vaccinology course, 2010.
AB  - A comprehensive 5-week vaccinology course was recently held in Paris (1 March-2
      April 2010) hosted by the Institut Pasteur, a world-renowned center for science
      and vaccinology. A total of 25 young scientists from different parts of the world
      participated and 63 world experts gave lectures in six specific modules that
      covered all aspects of vaccinology, from basic research to clinical studies.
      Students also had the opportunity to attend a 2-day "Pandemic Influenza
      Workshop". This article summarizes the issues discussed during this course and
      highlights the importance of global access to vaccines.

PMID- 20822347
TI  - MMR vaccination and disease elimination: the Finnish experience.
AB  - Measles, mumps and rubella (MMR) vaccinations have been included in Finland's
      national vaccination program as a two-dose schedule since 1982. Owing to the high
      (>95%) coverage of vaccinations, indigenous MMR diseases were eliminated from
      Finland by the mid-1990s. In 1982, the incidence of measles, mumps and rubella
      was 105, 43 and 64 per 100,000 population, respectively, but declined to 0.1 per
      100,000 population for all MMR diseases in 1995. Since then, the few cases of
      measles, mumps and rubella imported annually have not caused any outbreaks.
      Several research projects that started along with the vaccination campaign have
      provided important support throughout the program. The vaccine was proven to be
      safe, immunogenic and effective. Antibody follow-up has revealed that MMR vaccine
      induced antibodies wane over time, and concerns have arisen about the
      continuation of this good situation. High vaccination coverage, enhanced
      surveillance and preparedness to administer additional doses when needed are key
      factors for future success. Here we present an overview of MMR vaccinations and
      the Finnish experience of the MMR disease elimination process, and we describe
      surveillance activities in the era following elimination in Finland.

PMID- 20822346
TI  - Back to the future: covalent epitope-based HIV vaccine development.
AB  - Traditional HIV vaccine approaches have proved ineffective because the
      immunodominant viral epitopes are mutable and the conserved epitopes necessary
      for infection are not sufficiently immunogenic. The CD4 binding site expressed by
      the HIV envelope protein of glycoprotein 120 is essential for viral entry into
      host cells. In this article, we review the B-cell superantigenic character of the
      CD4 binding site as the cause of its poor immunogenicity. We summarize evidence
      supporting development of covalent immunization as the first vaccine strategy
      with the potential to induce an antibody response to a conserved HIV epitope that
      neutralizes genetically divergent HIV strains.

PMID- 20822348
TI  - Prime-boost immunization with poxvirus or adenovirus vectors as a strategy to
      develop a protective vaccine for HIV-1.
AB  - Challenges in the development of an effective HIV-1 vaccine are myriad with
      significant hurdles posed by viral diversity, the lack of a human correlate of
      protection and difficulty in creating immunogens capable of eliciting broadly
      neutralizing antibodies. The implicit requirement for novel approaches to these
      problems has resulted in vaccine candidates designed to elicit cellular and/or
      humoral immune responses, to include recombinant DNA, viral and bacterial
      vectors, and subunit proteins. Here, we review data from clinical studies
      primarily of poxvirus and adenovirus vector vaccines, used in a heterologous
      prime-boost combination strategy. Currently, this strategy appears to hold the
      most promise for an effective vaccine based on results from immunogenicity
      testing and nonhuman primate challenge models, as well as the modest efficacy
      recently observed in the Thai prime-boost trial.

PMID- 20822350
TI  - Generating humoral immune memory following infection or vaccination.
AB  - The production of long-lived, high-affinity antibodies forms the basis of many
      successful vaccination strategies. Although much is known of the proteins and
      pathways of the immune system that lead to the production of these antibodies,
      there are also many processes that remain unexplained or poorly explained. Some
      vaccines and infections lead to life-long protection while others elicit poor
      immune responses. Understanding the processes that lead to effective antibody
      production will allow us to recognize what aspects of the function of the immune
      system are subverted or compromised in the situation of ineffective vaccines and
      chronic persisting infection. This article will discuss the latest research into
      the mechanisms, pathways and proteins important for the production of long-lived
      humoral immunity, with a particular emphasis on the role of the germinal center,
      and how this research may be harnessed in the search for more effective vaccines
      and vaccination strategies.

PMID- 20822349
TI  - Progress and obstacles in vaccine development for the ehrlichioses.
AB  - Ehrlichia are tick-borne obligately intracellular bacteria that cause significant
      diseases in veterinary natural hosts, including livestock and companion animals,
      and are now considered important zoonotic pathogens in humans. Vaccines are
      needed for these veterinary and zoonotic human pathogens, but many obstacles
      exist that have impeded their development. These obstacles include understanding
      genetic and antigenic variability, influence of the host on the pathogen
      phenotype and immunogenicity, identification of the ehrlichial antigens that
      stimulate protective immunity and those that elicit immunopathology, development
      of animal models that faithfully reflect the immune responses of the hosts and
      understanding molecular host-pathogen interactions involved in immune evasion or
      that may be blocked by the host immune response. We review the obstacles and
      progress in addressing barriers associated with vaccine development to protect
      livestock, companion animals and humans against these host defense-evasive and
      cell function-manipulative, vector-transmitted pathogens.

PMID- 20822351
TI  - Nano-microparticles as immune adjuvants: correlating particle sizes and the
      resultant immune responses.
AB  - The development of novel immune adjuvants is emerging as a significant area of
      vaccine delivery based on the continued necessity to amplify immune responses to
      a wide array of new antigens that are poorly immunogenic. This article
      specifically focuses on the application of nanoparticles and microparticles as
      vaccine adjuvants. Many investigators are in agreement that the size of the
      particles is crucial to their adjuvant activities. However, reports on
      correlating the size of particle-based adjuvants and the resultant immune
      responses have been conflicting, with investigators on both sides of the fence
      with impressive data in support of the effectiveness of particles with small
      sizes (submicron) over those with larger sizes (micron) and vice versa, while
      other investigators reported data that showed submicron- and micron-sized
      particles are effective to the same degree as immune adjuvants. We have generated
      a list of biological, immunological and, more importantly, vaccine formulation
      parameters that may have contributed to the inconsistency from different studies
      and made recommendations on future studies attempting to correlate the size of
      particulate adjuvants and the immune responses induced. The information gathered
      could lead to strategies to optimize the performance of nano-microparticles as
      immune adjuvants.

PMID- 20822354
TI  - Comparative survival and cost of antifungal therapy: posaconazole versus standard
      antifungals in the treatment of refractory invasive aspergillosis.
AB  - BACKGROUND: Refractory invasive aspergillosis (IA) is a life-threatening
      condition. Cost of treatment, although secondary, is important if newer drugs are
      to be widely accepted. Posaconazole has been shown to have activity against
      aspergillosis. METHODS: Analyses were conducted to compare the effectiveness and
      cost of posaconazole 800 mg/day with those of standard antifungal therapy, using
      Walsh et al. 2007 data. All-cause mortality and total drug costs were analyzed
      for three patient groups: All Refractory, Refractory Non-neutropenic, and
      Refractory Neutropenic IA Patients. Comparative survival analysis using Kaplan
      Meier estimates after censoring data at 28, 42, 84, 182, and 365 days and Cox
      proportional hazard method was used to estimate hazard rates after controlling
      for difference in baseline neutropenia. For cost analysis, only antifungal drug
      acquisition cost was used. RESULTS: Significantly more of the 94 patients treated
      with posaconazole remained alive at every time point compared with the 68
      external control patients within the All Refractory group (p = 0.0001). Similar
      results were obtained for the other two groups. For the posaconazole-treated
      patients mean total drug costs were $11846 (+/-$12406), $12642 (+/-$11811), and
      $8903 (+/-$14345), and for the external controls total drug costs were $35537 (+/
      $73059), $48097 (+/-$88702), and $13556 (+/-$16324) for the All Refractory,
      Refractory Non-neutropenic, and Neutropenic IA groups, respectively. Key
      limitations of the study included noninclusion of hospitalization or other drug
      costs, low patient numbers beyond 84 days, and the fact that the Walsh et al.
      2007 study was completed before other newer antifungal agents (such as
      voriconazole and caspofungin) were available. CONCLUSIONS: Posaconazole appears
      to confer a survival benefit and reduced total drug cost compared with standard
      antifungal therapy, such as amphotericin B (lipid and nonlipid formulations),
      itraconazole, or both, to treat patients with probable or proven refractory IA.

PMID- 20822352
TI  - Anti-cocaine vaccine development.
AB  - Cocaine abuse is an ongoing and serious problem that has led to the growth of a
      brutal criminal enterprise, particularly in the Americas and Europe. At present,
      there are no effective pharmacological agents available to treat the addiction by
      blocking cocaine or reversing its effects. In order to help motivated addicts
      conquer their addiction, vaccines against cocaine are being developed and one has
      progressed to clinical trials. This article will discuss the concept of antidrug
      vaccines in general, the successes and limitations of the various anti-cocaine
      vaccine approaches, the results of the clinical trials with an anti-cocaine
      vaccine and some new vaccine-mediated approaches to combat cocaine addiction.

PMID- 20822358
TI  - Suicide in films: the impact of suicide portrayals on nonsuicidal viewers' well
      being and the effectiveness of censorship.
AB  - The effects of suicide films on recipients' emotional and mental state, as well
      as the influence of censorship, was studied. Nonsuicidal subjects watched the
      original or a censored version of a suicide film or a drama without suicide. Data
      were collected by questionnaires. The viewing led to a deterioration of mood and
      an increase in inner tension and depression scores, but also to a rise in self
      esteem and life satisfaction and to a drop in suicidality. There were no relevant
      differences between the film groups. The more a subject identified with the
      protagonist, the greater were the negative effects.

PMID- 20822357
TI  - Increased risk of suicidal ideation in smokers and former smokers compared to
      never smokers: evidence from the Baltimore ECA follow-up study.
AB  - The incidence rate of suicidal ideation among current and former smokers versus
      never smokers is not known. In this study, the age-adjusted incidence of suicidal
      ideation was highest among current smokers, followed by former, then never
      smokers. The adjusted hazard for suicide ideation was 2.22 (95%CI = 1.48, 3.33)
      and 1.19 (95%CI = 0.78, 1.82) for current and former smokers, respectively,
      compared to never smokers. Results indicate that current smokers have increased
      risks of suicidal ideation above and beyond the risk for never and former smokers
      regardless of age, gender, history of depressive disorder or anxiety symptoms,
      and alcohol abuse/dependence. Smoking cessation might be beneficial for some
      suicide prevention efforts.

PMID- 20822359
TI  - Patient suicide: a survey of therapists' reactions.
AB  - A substantial proportion of therapists will at some point in their professional
      life experience the loss of a patient to suicide. Our aims were to assess how
      therapists react to patient's suicide over time and which factors contribute to
      the reaction. One third of the therapists, mostly women, suffer from severe
      distress. The impact is not different for therapists in institutional settings
      and therapists in private practice. The item "overall distress" immediately after
      the suicide predicts emotional reactions and changes in behavior. Our data
      suggest that identifying the severely distressed subgroup could be done using a
      visual analogue scale for overall distress. As a consequence, more specific and
      intensified help could be provided to these individuals.

PMID- 20822360
TI  - Aggression and the risk for suicidal behaviors among children.
AB  - Two subtypes of aggression--reactive and proactive--were examined to see how they
      relate to suicidal behaviors among young children admitted for acute psychiatric
      inpatient care. The children and their parents completed self-report
      questionnaires/interviews. Regression analyses revealed that depressed girls who
      scored higher on reactive aggression reported more suicidal behaviors; whereas
      proactive aggression did not relate to suicidal behaviors for either boys or
      girls.

PMID- 20822361
TI  - Myths and facts about suicide from individuals involved in suicide prevention.
AB  - Myth-busting, in which a so-called myth is presented and dispelled by facts, is
      used in suicide prevention gatekeeper trainings such as QPR. Evidence from other
      areas of public health shows this technique leads to memory for myths and not
      facts. An internet survey was used to determine if the "myths" and "facts"
      presented in QPR are endorsed as such by the suicidology community and to
      determine if demographics influenced statement identification. Overall,
      statements did reflect the opinions of the suicidology community and any type of
      training increased correct identification. Future research should focus on
      whether myth-busting is an appropriate strategy for suicidology.

PMID- 20822362
TI  - Factors of early suicide after discharge: a national linkage study for suicide
      victims in Taiwan.
AB  - Patients recently discharged from psychiatric inpatient care have a higher
      suicide rate. The study aimed to identify the characteristics associated with
      early suicide of those patients discharged from psychiatric wards in Taiwan. The
      results indicated that among 672 suicide victims who died within one year post
      discharge from psychiatric wards in Taiwan between 2000 and 2004, diagnosis of
      schizophrenia, shorter disease duration, and co-morbidity with cancer were all
      significantly associated with suicide occurring within one month of discharge.
      Clinical diagnosis of psychiatric disorders, recent psychiatric diagnosis, and co
      morbidity with severe physical illnesses should receive special monitoring for
      potential suicide after discharge.

PMID- 20822363
TI  - Autobiographical memory and suicide attempts in schizophrenia.
AB  - According to the cry of pain model of suicidal behavior, an over-general
      autobiographical memory function is often found in suicide attempters. The model
      has received empirical support in several studies, mainly of depressed patients.
      The present study investigated whether deficits in autobiographical memory may be
      associated with an increased frequency of suicide attempts in patients with
      schizophrenia. We found support for our hypothesis that patients with
      schizophrenia and previous suicide attempts have an over-generalized
      autobiographical memory compared to patients with schizophrenia without previous
      suicide attempts. Adjustment for sociodemographic and clinical variables did not
      change the results.

PMID- 20822364
TI  - Rural-urban differences in suicide rates for current patients of a public mental
      health service in Australia.
AB  - Rural versus urban rates of suicide in current patients of a large area mental
      health service in Australia were compared. Suicide deaths were identified from
      compulsory root cause analyses of deaths, 2003-2007. Age-standardized rates of
      suicide were calculated for rural versus urban mental health service and compared
      using variance of age-standardized rates with 95% confidence intervals. There
      were 44 suicides and the majority (62%) were rural. Only urban patients used
      jumping from heights as a method of suicide (4/17; p = 0.02). Rural patients had
      2.7 times higher rates of suicide, similar to findings for rural versus urban
      community suicides and may reflect the underlying community rates, differences in
      mental health service delivery, or socioeconomic disadvantage.

PMID- 20822365
TI  - Age-specific characteristics of serious suicide attempters in China.
AB  - Characteristics of four age groups of patients with medically serious suicide
      attempts from nine general hospitals in China (N = 617) were compared. There were
      no significant age-group differences by residence (rural vs. urban), method of
      attempt, proportion with prior attempts, or level of family functioning.
      Attempters < or = 20 years of age were less likely to use alcohol at the time of
      the attempt. Attempters age 20-44 years had less regular contact with family
      members but were more likely to make the attempt in the presence of someone else.
      And attempters > or = 45 years were more likely to have high suicidal intent,
      lower quality of life, mood disorders, and substance abuse disorders. These
      results highlight the need for age-specific intervention programs for suicide
      attempters.

PMID- 20822366
TI  - Awareness effects of a youth suicide prevention media campaign in Louisiana.
AB  - Research on the efficacy of mediated suicide awareness campaigns is limited. The
      impacts of a state-wide media campaign on call volumes to a national hotline were
      analyzed to determine if the advertisements have raised awareness of the hotline.
      We use a quasi-experimental design to compare call volumes from ZIP codes where
      and when the campaign is active with those where and when the campaign is not
      active. Multilevel model estimates suggest that the campaign appears to have
      significantly and substantially increased calls to the hotline. Results from this
      study add evidence to the growing public health literature that suggests that
      mediated campaigns can be an effective tool for raising audience awareness.

PMID- 20822367
TI  - Prior health care utilization patterns and suicide among U.S. Army soldiers.
AB  - Suicides among U.S. Army soldiers are increasing and, in January 2009, outpaced
      deaths due to combat. For this study, 1,873 army suicides identified through
      death, inpatient, and emergency room records were matched with 5,619 controls. In
      multivariate models, older, male, White, single, and enlisted soldiers with a
      prior injury (OR = 2.04, 95% CI = 1.64-2.54), alcohol (OR = 3.41, 95% CI = 2.32
      4.99), or mental health hospitalization (OR = 6.62, 95% CI = 4.77-9.20) were at
      increased risk for suicide. Risk was greatest immediately following diagnoses,
      but remained elevated even after 5 or more years of follow-up. Most injury
      hospitalizations were unintentional but, nonetheless, significantly associated
      with suicide. Interactions indicate soldiers with both mental health and injury
      history are particularly vulnerable.

PMID- 20822368
TI  - Risk factors for attempting suicide in heroin addicts.
AB  - In order to examine risk factors for attempting suicide in heroin dependent
      patients, a group of 527 abstinent opiate dependent patients had a psychiatric
      interview and completed the Childhood Trauma Questionnaire. Patients who had or
      had never attempted suicide were compared on putative suicide risk factors. It
      was found that 207 of the 527 heroin abusers (39.3%) had attempted suicide.
      Attempters were younger; more were female, reported childhood trauma, a family
      history of suicidal behavior, a history of aggression, treatment with
      antidepressant medication, and alcohol and cocaine dependence. Logistic
      regression revealed that a family history of suicidal behavior, alcohol
      dependence, cocaine dependence, and treatment with antidepressant medication were
      significant predictors of attempting suicide. These results suggest that
      attempting suicide is common among opiate dependent patients and that both distal
      and proximal risk factors may play a role.

PMID- 20822369
TI  - A natural product telomerase activator as part of a health maintenance program.
AB  - Most human cells lack sufficient telomerase to maintain telomeres, hence these
      genetic elements shorten with time and stress, contributing to aging and disease.
      In January, 2007, a commercial health maintenance program, PattonProtocol-1, was
      launched that included a natural product-derived telomerase activator (TA-65(r),
      10-50 mg daily), a comprehensive dietary supplement pack, and physician
      counseling/laboratory tests at baseline and every 3-6 months thereafter. We
      report here analysis of the first year of data focusing on the immune system. Low
      nanomolar levels of TA-65(r) moderately activated telomerase in human
      keratinocytes, fibroblasts, and immune cells in culture; similar plasma levels of
      TA-65(r) were achieved in pilot human pharmacokinetic studies with single 10- to
      50-mg doses. The most striking in vivo effects were declines in the percent
      senescent cytotoxic (CD8(+)/CD28(-)) T cells (1.5, 4.4, 8.6, and 7.5% at 3, 6, 9,
      and 12 months, respectively; p = not significant [N.S.], 0.018, 0.0024, 0.0062)
      and natural killer cells at 6 and 12 months (p = 0.028 and 0.00013,
      respectively). Most of these decreases were seen in cytomegalovirus (CMV)
      seropositive subjects. In a subset of subjects, the distribution of telomere
      lengths in leukocytes at baseline and 12 months was measured. Although mean
      telomere length did not increase, there was a significant reduction in the
      percent short (<4 kbp) telomeres (p = 0.037). No adverse events were attributed
      to PattonProtocol-1. We conclude that the protocol lengthens critically short
      telomeres and remodels the relative proportions of circulating leukocytes of
      CMV(+) subjects toward the more "youthful" profile of CMV(-) subjects. Controlled
      randomized trials are planned to assess TA-65(r)-specific effects in humans.

PMID- 20822370
TI  - Silver nanoparticles enhance thrombus formation through increased platelet
      aggregation and procoagulant activity.
AB  - Despite the wide use of silver nanoparticles (nano Ag), its toxicity still
      remains poorly understood. In this report, nano Ag induced an increase in
      platelet aggregation and procoagulant activation which are the key contributors
      to thrombotic diseases. In freshly isolated human platelets, nano Ag induced
      platelet aggregation and procoagulant activation evident by increased
      phosphatidylserine exposure and thrombin generation. Interestingly, the sub
      threshold level of thrombin enhanced nano Ag-induced platelet activation
      significantly indicating that the prothrombotic effects of nano Ag might be
      further potentiated in activated platelets. An increase in intracellular calcium
      mediated nano Ag induced platelet activation and P-selectin expression, and
      serotonin release was also enhanced by nano Ag. Consistent with the in vitro
      results, exposure to nano Ag (0.05-0.1 mg/kg i.v. or 5-10 mg/kg intratracheal
      instillation) in vivo enhanced venous thrombus formation, platelet aggregation,
      and phosphatidylserine externalization ex vivo in rats suggesting that nano Ag,
      indeed, does enhance thrombus formation through platelet activation.

PMID- 20822371
TI  - Latent simian varicella virus reactivates in monkeys treated with tacrolimus with
      or without exposure to irradiation.
AB  - Simian varicella virus (SVV) infection of primates resembles human varicella
      zoster virus (VZV) infection. After primary infection, SVV becomes latent in
      ganglia and reactivates after immunosuppression or social and environmental
      stress. Herein, natural SVV infection was established in 5 cynomolgus macaques
      (cynos) and 10 African green (AG) monkeys. Four cynos were treated with the
      immunosuppressant tacrolimus (80 to 300 &#x03BC;g/kg/day) for 4 months and 1 was
      untreated (group 1). Four AG monkeys were exposed to a single dose (200 cGy) of x
      irradiation (group 2), and 4 other AG monkeys were irradiated and treated with
      tacrolimus for 4 months (group 3); the remaining 2 AG monkeys were untreated.
      Zoster rash developed 1 to 2 weeks after tacrolimus treatment in 3 of 4 monkeys
      in group 1, 6 weeks after irradiation in 1 of 4 monkeys in group 2, and 1 to 2
      weeks after irradiation in all 4 monkeys in group 3. All monkeys were euthanized
      1 to 4 months after immunosuppression. SVV antigens were detected
      immunohistochemically in skin biopsies as well as in lungs of most monkeys. Low
      copy number SVV DNA was detected in ganglia from all three groups of monkeys,
      including controls. RNA specific for SVV ORFs 61, 63, and 9 was detected in
      ganglia from one immunosuppressed monkey in group 1. SVV antigens were detected
      in multiple ganglia from all immunosuppressed monkeys in every group, but not in
      controls. These results indicate that tacrolimus treatment produced reactivation
      in more monkeys than irradiation and tacrolimus and irradiation increased the
      frequency of SVV reactivation as compared to either treatment alone.

PMID- 20822372
TI  - Dysbindin gene (DTNBP1) in major depressive disorder (MDD) patients: lack of
      association with clinical phenotypes.
AB  - OBJECTIVES: Dystrobrevin binding protein 1 (Dysbindin) is a plausible candidate
      gene for major depressive disorders (MDD) due to its involvement in synaptic
      signaling, plasticity and localization in the brain. METHODS: Two intronic SNPs
      of DTNBP1; rs760761 (P1320) and rs2619522 (P1763) were analyzed in 206 patients
      with DSM-IV MDD to investigate the functional impact of genotypes on
      susceptibility for depression and some clinical phenotypes. The Sequenom iPLEX
      assay (Sequenom, Cambridge, MA) was used for genotyping. RESULTS AND CONCLUSIONS:
      Despite the limited power of analysis, our results showed that these two SNPs in
      DTNPB1 gene were not related to clinical phenotypes such as melancholia, age at
      onset, suicidality and co-morbid anxiety disorders, as well as to treatment
      response phenotypes.

PMID- 20822373
TI  - Salivary dehydroepiandrosterone, but not cortisol, is associated with attention
      deficit hyperactivity disorder.
AB  - OBJECTIVES: The purposes of this study were to determine whether salivary levels
      of dehydroepiandrosterone (DHEA) and cortisol are associated with attention
      deficit hyperactivity disorder (ADHD) or correlated with performance on the
      Continuous Performance Test (CPT). METHODS: Fifty ADHD patients and 50 age- and
      gender-matched controls aged between 6 and 12 years were included in this cross
      sectional study. DHEA and cortisol levels were determined from saliva samples
      collected by the passive drool method at 08:00 h. ADHD patients subsequently
      performed a computerized Continuous Performance Test (CPT). ADHD symptoms were
      evaluated with the Swanson, Nolan, and Pelham, Version IV Scale for ADHD (SNAP
      IV), completed by the patients' parents, and with the ADHD Rating Scale (ADHD
      RS), administered by a child psychiatrist. RESULTS: Saliva DHEA levels and
      DHEA/cortisol ratios differed significantly between ADHD patients and controls.
      Among ADHD patients, saliva DHEA levels and DHEA/cortisol ratios were
      independently correlated with composite scores of CPT distractibility and CPT
      impulsivity. Basal levels of cortisol were not significantly associated with
      ADHD. CONCLUSIONS: DHEA, but not the cortisol basal level, may be a biological
      laboratory marker for ADHD, particularly for performance on the CPT. Both the
      causal relationship between DHEA and ADHD and the role of DHEA in treating ADHD
      require further investigation.

PMID- 20822374
TI  - Who receives anticoagulant treatment with warfarin and why? A population-based
      study in Finland.
AB  - OBJECTIVE: To ascertain the age and gender distribution of patients receiving
      anticoagulant (AC) treatment with warfarin, and to establish the prevalence of AC
      treatment and its indications among the Finnish population. DESIGN: A cross
      sectional study in which the patients were identified from the patient records of
      health centres. SETTING: Primary health care in the Hospital District of South
      Ostrobothnia in Finland. PATIENTS: Those inhabitants of 15 municipalities in the
      study area who received AC treatment with warfarin on 1 April 2004. The total
      number of inhabitants was 132 621 at the end of 2003. MAIN OUTCOME MEASURES:
      Patient age and gender distributions, the prevalence of AC treatment in the study
      area, and indications for AC treatment. RESULTS: Altogether 2389 patients were
      identified, 51.4% of them men. The mean age of the patients was 72.4 years. The
      prevalence of AC treatment was 1.8%; when age-adjusted to match the Finnish
      population it was 1.64%. The proportion of men receiving AC treatment was higher
      than that of women in all age groups. Atrial fibrillation (AF) was the most
      common main (60.2%) and second (7.2%) indication for AC treatment. CONCLUSION:
      Compared with Finnish figures 12 years earlier the prevalence of AC treatment has
      more than doubled, and the proportion of AF among indications has increased from
      47% to 67%. New current care guidelines on AF and the increasing proportion of
      the elderly among the population are probable explanations.

PMID- 20822375
TI  - Considerations made by the general practitioner when dealing with sick-listing of
      patients suffering from subjective and composite health complaints.
AB  - OBJECTIVES: To explore GPs' considerations in decision-making regarding sick
      listing of patients suffering from SHC. DESIGN: Qualitative analysis of data from
      nine focus-group interviews. SETTING: Three cities in different regions of
      Norway. Participants. A total of 48 GPs (31 men, 17 women; aged 32-65)
      participated. The GPs were recruited when invited to a course dealing with
      diagnostic practice and assessment of sickness certificates related to patients
      with composite SHCs. RESULTS: Decisions on sick-listing patients with SHCs were
      regarded as a very challenging task. Trust in the patient's own story and self
      judgement was deemed crucial, but many GPs missed hard evidence of illness and
      loss of function. Several factors that might influence decision-making were
      identified: the patients' ability to present their story to evoke sympathy, the
      GP's prior knowledge of the patient, and the GPs' own experience as a patient and
      their tendency to avoid conflicts. The approach to the task of sick-listing
      differed from patient-led cooperation to resistant confrontation. CONCLUSION AND
      IMPLICATIONS: Issuing sickness certification in patients with composite health
      complaints is considered challenging and burdensome. It is seen as mainly patient
      driven, and the decisions vary according to GPs' attitudes, beliefs, and
      personalities. Guiding the GPs to a more focused awareness of the decision
      process should be considered.

PMID- 20822376
TI  - Efficacy and cost-effectiveness of consensus interferon monotherapy with high
      dose induction for hepatitis C patients with genotype 2.
AB  - OBJECTIVE: Several treatment strategies for patients with chronic hepatitis C
      have been compared mainly in terms of their efficacy, and it has been found that
      pegylated interferon (IFN) plus ribavirin has become the standard therapy, but
      aged patients may not tolerate ribavirin and the cost-effectiveness of treatment
      should also be further considered. We conducted a study to evaluate the efficacy,
      safety, and cost-effectiveness of consensus IFN monotherapy with high-dose
      induction for patients with chronic hepatitis C in clinical practice. MATERIAL
      AND METHODS: We consecutively enrolled 104 patients with chronic hepatitis C.
      Patients were scheduled to receive 12 or 18 MUg of consensus IFN daily for 2
      weeks, then three times a week for 22 weeks. Efficacy, safety, and cost
      effectiveness were assessed. A Markov model was developed to investigate cost
      effectiveness in patients with chronic hepatitis C treated by different IFN-based
      treatment strategies. RESULTS: Of the 104 study patients, a sustained virological
      response (SVR) was achieved in 66 (63%). Logistic regression analysis revealed
      that genotype 2, lower hepatitis C virus RNA levels, and patient age were
      independently associated with SVR. The response rate was significantly higher in
      patients with genotype 2 (51/66, 77%) versus genotype 1 (15/38, 40%). Cost
      effectiveness analysis in patients with genotype 2 revealed that high-dose
      induction with consensus IFN monotherapy was as highly cost-effective as
      pegylated IFN plus ribavirin. CONCLUSION: Consensus IFN monotherapy with high
      dose induction shows high efficacy and cost-effectiveness in chronic hepatitis C
      patients with genotype 2 infection. Thus, it may be a reliable alternative in
      aged patients and for those excluded from standard combination therapy.

PMID- 20822377
TI  - Up-regulated myeloid-derived suppressor cell contributes to hepatocellular
      carcinoma development by impairing dendritic cell function.
AB  - OBJECTIVE: Defective immune function is an important cause of tumor development.
      Accumulation of myeloid-derived suppressor cell (MDSC) associated with inhibition
      of dendritic cell (DC) function is one of the major immunological abnormalities
      in cancer. However, the molecular mechanism of the phenomenon remains unclear.
      MATERIAL AND METHODS: We evaluated T cell stimulatory activity and interleukin
      (IL)-12 production of DC in a mouse model of liver cancer (hepatocellular
      carcinoma [HCC] mice). Then we detected the frequency of MDSC in spleen,
      peripheral blood (PB), lymph node (LN) and tumor tissue of HCC mice and its
      potential mechanisms. We also evaluated IL-10 production of MDSC and mechanism by
      which MDSC inhibit DC function. RESULTS: Toll-like receptor (TLR)-ligand (LPS,
      CpG, poly(I:C))-induced IL-12 production of DC was decreased in HCC mice compared
      with control. The T cell stimulatory activity of DC was lower in HCC mice than in
      controls. Meanwhile, an increase in the frequency of MDSC in tumor development
      was detected in spleen, PB, LN and tumor, and the IL-10 levels were higher in HCC
      mice derived MDSC than in control. Furthermore, the MDSC inhibited TLR-ligand
      induced IL-12 production of DC by IL-10 production and suppressed T cell
      stimulatory activity of DC. Finally, we demonstrated that the increase in the
      frequency of MDSC was mediated by MyD88-NF-kB pathway. CONCLUSIONS: Our study
      suggests a new role for MDSCs in HCC development by suppressing host immune
      responses, and these findings have important implications when designing
      immunotherapy protocols.

PMID- 20822378
TI  - The acquisition of consonants in Quebecois French: a cross-sectional study of pre
      school aged children.
AB  - This study provides a systematic description of French consonant acquisition in a
      large cohort of pre-school aged children: 156 children aged 20-53 months
      participated in a picture-naming task. Five analyses were conducted to study
      consonant acquisition: (1) consonant inventory, (2) consonant accuracy, (3)
      consonant acquisition, (4) a comparison of consonant inventory to consonant
      acquisition, and (5) a comparison to English cross-sectional data. Results
      revealed that more consonants emerge at an earlier age in word initial position,
      followed by medial position, and then word final position. Consonant accuracy
      underwent the greatest changes before the age of 36 months, and achieved a
      relative plateau towards 42 months. The acquisition of consonants revealed that
      four early consonants were acquired before the age of 36 months (i.e., /t, m, n,
      z/); 12 intermediate consonants were acquired between 36 and 53 months (i.e., /p,
      b, d, k, g, nu, f, v, [symbol in text], l, w, ch/); and four consonants were
      acquired after 53 months (/s, ze, ?, j/). In comparison to English data, language
      specific patterns emerged that influence the order and pace of phonological
      acquisition. These findings highlight the important role of language specific
      developmental data in understanding the course of consonant acquisition.

PMID- 20822379
TI  - Prostate cancer imaging: what the next decade holds.

PMID- 20822380
TI  - Microspheres for radioembolization of liver malignancies.

PMID- 20822382
TI  - ExAblate magnetic resonance-guided focused ultrasound system in multiple body
      applications.
AB  - Focused ultrasound surgery (FUS) is a completely noninvasive method of thermally
      destroying a target tissue while sparing adjacent tissues and organs. Treatment
      is relatively painless and can be carried out under conscious sedation on an out
      patient basis. The combination of magnetic resonance guidance with FUS (MRgFUS)
      provides the ability to plan and monitor treatments in near real-time, further
      increasing the safety profile of MRgFUS. This technology provides a very
      personalized treatment, adjusted to the individual patient anatomy, pathology and
      treatment response, hence it meets the needs of patients, as well as of
      physicians. MRgFUS has been used extensively in the successful treatment of
      uterine fibroids, and has been shown to be an effective treatment in the breast
      and in bone metastases in smaller scale studies. It shows great potential in the
      treatment of prostate and liver tumors, as well as in the brain and facet joints.

PMID- 20822383
TI  - Titanium-nitride-oxide-coated Titan-2 bioactive coronary stent: a new horizon for
      coronary intervention.
AB  - The introduction of drug-eluting stents has revolutionized the field of
      interventional cardiology, since it has reduced the incidence of restenosis by 50
      70%. However, recent worrisome data from registries and meta-analyses emphasized
      higher rates of late and very late stent thrombosis associated with drug-eluting
      stents. The recently introduced titanium-nitride-oxide-coated stent (Titan-2) has
      demonstrated an excellent biocompatibility, as reflected by lower rates of
      platelet aggregation and fibrin deposition, and better endothelialization.
      Preclinical and clinical trials and registries involving both real-life
      unselected populations and populations with the most challenging patient and
      lesion characteristics have shown a low rate of major adverse cardiac events in
      the long-term, with a restenosis rate comparable with that of drug-eluting
      stents, with the virtual absence of stent thrombosis.

PMID- 20822384
TI  - Self-treatment of benign paroxysmal positional vertigo with DizzyFix, a new
      dynamic visual device.
AB  - Benign paroxysmal positional vertigo is one of the most common disorders of the
      vestibular system. It is characterized by episodes of recurrent vertigo triggered
      by head movements or position changes associated with nystagmus. There is
      scientific evidence that in the majority of cases this condition responds well to
      the particle repositioning maneuver (PRM) correctly performed by the physician.
      However, the PRM needs to be repeated in approximately 30% of the cases. Although
      the maneuver is simple, patients often find it difficult to perform correctly as
      self-treatment, with the result that it fails to bring about an improvement in
      the symptoms. DizzyFix (Clearwater Clinical Limited, Canada) is the name given to
      a new dynamic visual device designed to provide a visual representation of the
      PRM based on the canalith theory. The DizzyFiX consists of a specially curved
      acrylic tube containing a nontoxic viscous fluid and a bead, the purpose of which
      is to help the patient and the inexperienced physician to perform the PRM
      correctly. A randomized clinical trial has shown that it reliably enables the
      maneuver to be performed correctly, and a study investigating the effectiveness
      of patient self-treatment of benign paroxysmal positional vertigo with the device
      in comparison with standard office treatment revealed both techniques to be
      equally effective. The device has now been approved by the US FDA.

PMID- 20822385
TI  - The comparative safety of bare-metal and drug-eluting intracoronary stents.
AB  - Bare-metal stents were a significant advance over percutaneous transluminal
      coronary angioplasty in the treatment of atherosclerotic coronary artery disease.
      However, bare-metal stents are plagued by a restenosis rate of approximately 30%.
      First-generation drug-eluting stents greatly reduce restenosis but are associated
      with a troublesome persistence of late thrombotic events. Stent thrombosis is a
      devastating clinical event, with high mortality rates. While the superior
      efficacy of drug-eluting stents is unquestioned, the relative safety of bare
      metal and drug-eluting stents has been hotly debated. This article will address
      the safety of bare-metal and drug-eluting stents, and will describe current and
      future stent systems that promise to maintain current efficacy, while reducing
      thrombosis risk even further.

PMID- 20822386
TI  - Perioperative assessment of platelet function in patients under antiplatelet
      therapy.
AB  - Platelets play a central role in primary hemostasis. Analysis of platelet
      function is therefore a cornerstone in the global assessment of the coagulation
      status in the perioperative setting, primarily in patients receiving antiplatelet
      medication, such as cyclooxygenase-1 inhibitors, adenosine diphosphate
      antagonists and glycoprotein IIb/IIIa inhibitors. In these patients, knowledge of
      residual platelet function is highly warranted in order to maintain an optimal
      and individual balance perioperatively between platelet function and inhibition -
      that is, bleeding and thrombosis. Traditional laboratory-based assays, such as
      light-transmission aggregometry and flow cytometry, are the clinical standards of
      platelet function testing today. Light-transmission aggregometry is one of the
      most widely used tests to identify and diagnose defects in platelet function. The
      majority of the conventional laboratory-based techniques are labor intensive,
      costly and time consuming, and require a high degree of experience and expertise
      to perform and interpret. Therefore, new automated technologies have been
      developed to measure platelet function more rapidly and easily, and several
      techniques can be used at the bedside, including whole blood aggregometry, high
      shear-induced platelet function assessment or viscoelastic measurement
      techniques. All methods assessing platelet function are summarized and their
      limitations are discussed in this article, emphasizing their perioperative use.

PMID- 20822387
TI  - Novel wound sealants: biomaterials and applications.
AB  - Wound sealants provide an excellent alternative for closing surgical and non
      surgical wounds, as well as stopping external bleeding for prehospital trauma
      injuries. Numerous biomaterials have been investigated to address specific
      requirements for their use as suitable wound sealants. This article focuses on
      the development of new wound sealant biomaterials and recent advances in the
      surgical applications of wound sealants. In the past 5 years, many new sealant
      materials had been reported, including keratin, mussel-adhesive proteins,
      dendrimers and in situ-forming hydrogels. Fibrin sealants remain the most
      clinically studied for a variety of surgical procedures, while clinical
      experience with wound sealants for orthopedic surgery is limited. Both liquid and
      solid wound sealants have been developed and found effective by possessing strong
      adhesive properties. Biocompatible and biodegradable wound sealants hold much
      promise in eventually replacing sutures in most surgical procedures.

PMID- 20822388
TI  - Aqueous shunts in the treatment of glaucoma.
AB  - The main goal of surgical glaucoma treatment is to reduce the intraocular
      pressure. The standard procedure over the past 40 years has been trabeculectomy,
      first described in 1968. This procedure comes with a very high risk profile, and
      results in moderate long-term results at best. Tube shunt devices were introduced
      as an alternate means to divert fluid out of the glaucomatous eye, attempting to
      improve upon the poor long-term outcomes of trabeculectomy, particularly in
      refractory cases that had failed attempts at prior glaucoma surgeries. They are
      currently available in a handful of different designs and have evolved from
      representing a second- or third-line treatment in refractory cases, to their
      current standing of accepted first-line surgical intervention for many surgeons.
      The designs of the aqueous shunts are simple and installation involves
      straightforward principles of ophthalmic surgery. Recent additions to the
      literature, as well as the development of the Ex-PRESS Miniature Shunt, are
      changing the way shunts are employed in the treatment algorithm for surgical
      glaucoma. The outcomes of these procedures are encouraging, and support their use
      as first-line surgical options for the treatment of adult and juvenile glaucoma.

PMID- 20822389
TI  - Development of speech prostheses: current status and recent advances.
AB  - Brain-computer interfaces (BCIs) have been developed over the past decade to
      restore communication to persons with severe paralysis. In the most severe cases
      of paralysis, known as locked-in syndrome, patients retain cognition and
      sensation, but are capable of only slight voluntary eye movements. For these
      patients, no standard communication method is available, although some can use
      BCIs to communicate by selecting letters or words on a computer. Recent research
      has sought to improve on existing techniques by using BCIs to create a direct
      prediction of speech utterances rather than to simply control a spelling device.
      Such methods are the first steps towards speech prostheses as they are intended
      to entirely replace the vocal apparatus of paralyzed users. This article outlines
      many well known methods for restoration of communication by BCI and illustrates
      the difference between spelling devices and direct speech prediction or speech
      prosthesis.

PMID- 20822390
TI  - Endoscopic stenting for palliation of malignant biliary obstruction.
AB  - Malignant biliary obstruction results in jaundice, often with symptoms that
      decrease the quality of life. Biliary stent placement has largely supplanted
      surgical bypass for palliation of malignant biliary obstruction. Traditional
      rigid plastic stents are commonly used, inexpensive and easily removed, although
      with limited duration of stent patency. Self-expandable metal stents (SEMS)
      attain larger luminal diameters and provide longer patency than traditional rigid
      plastic stents in patients with distal bile duct obstruction. SEMS are composed
      of a variety of metals and can be uncoated, partially covered, or fully covered.
      Data do not support a prolongation of patency with covered SEMS for distal
      obstruction, although they have the potential for removability. The data to
      support SEMS for palliation of hilar biliary obstruction are not as convincing
      and reintervention for stent occlusion can be difficult. In this article, the
      design and performance of expandable metal stents for treatment of malignant
      biliary obstruction will be reviewed.

PMID- 20822391
TI  - Energy sources and their development for application in medical devices.
AB  - Electronic medical devices have become an indispensable part of modern
      healthcare. Currently, a wide variety of electronic medical devices are being
      used to monitor physiological parameters of the body, perform therapy and
      supplement or even entirely replace complex biological functions. Cardiac
      pacemakers, cardioverter-defibrillators and cochlear implants are a few examples
      of such medical devices. Proper functionality of these devices relies heavily on
      the continuous supply of a sufficient amount of electricity to them. In this
      sense, a reliable, safe and convenient method for the provision of energy is very
      crucial. Various approaches have been developed to fulfil the divergent and
      challenging energy requirements of medical devices. In this article, we present a
      brief overview of the energy requirements of medical devices and review the
      existing and emerging energy sources for application in these devices,
      particularly wearable and implantable devices.

PMID- 20822392
TI  - An overview of temperature monitoring devices for early detection of diabetic
      foot disorders.
AB  - Diabetic foot complications are associated with substantial costs and loss of
      quality of life. This article gives an overview of available and emerging devices
      for the monitoring of foot temperature as a means of early detection of foot
      disorders in diabetes. The aim is to describe the technologies and to summarize
      experiences from experimental use. Studies show that regular monitoring of foot
      temperature may limit the incidence of disabling conditions such as foot ulcers
      and lower-limb amputations. Infrared thermometry and liquid crystal thermography
      were identified as the leading technologies in use today. Both technologies are
      feasible for temperature monitoring of the feet and could be used as a complement
      to current practices for foot examinations in diabetes.

PMID- 20822395
TI  - Mastering social and organization goals: strategy use by two children with
      Asperger syndrome during cognitive orientation to daily occupational performance.
AB  - Preliminary data supports the effectiveness of Cognitive Orientation to (daily)
      Occupational Performance (CO-OP) for children with Asperger syndrome (AS).
      Children with AS often experience social and organizational difficulties spanning
      daily occupations. This case study explored the pattern of Global Strategies and
      Domain-Specific Strategies (DSS) use, the type of guidance, and dimensions of
      time on task used by two children with AS (aged 10 and 12 years) in addressing
      social and organizational goals during the CO-OP intervention. Coding of the
      videotaped CO-OP sessions suggested that both children (a) utilized all the
      Global strategies, particularly "understanding the context" and "plan"; (b) used
      six common DSS, namely transitional supports, affective supports, attending, task
      specification, task modification, and supplementing task knowledge, with task
      specification being most prominent; (c) required minimal guidance while "doing";
      and (d) engaged in considerable time "talking about the task." The results
      provide initial insights into strategies that may enable children with AS to
      achieve social and organizational goals.

PMID- 20822396
TI  - Development and pilot testing of the challenge module: a proposed adjunct to the
      Gross Motor Function Measure for high-functioning children with cerebral palsy.
AB  - The aim was to develop a Challenge Module (CM) as a proposed adjunct to the Gross
      Motor Function Measure for children with cerebral palsy who have high-level motor
      function. Items were generated in a physiotherapist (PT) focus group. Item
      reduction was based on PTs' ratings of item importance and safety via online
      surveys. The proposed CM items were pilot-tested with children in Gross Motor
      Function Classification System Level I. The focus group identified 35 items for
      consideration. The first item-reduction survey (n = 86 PT respondents) resulted
      in 20 items. A second survey yielded two additional items. Seven pilot-test
      participants (6-14 years) had a CM total mean score of 74.5% (SD = 19.4). Three
      easy items were subsequently removed and two items combined. Of seven additional
      items suggested by the children during testing, two were accepted in a third item
      reduction survey. The final result was a 20-item CM to evaluate advanced motor
      skills. The CM requires refinement through Rasch scaling and formal validation.

PMID- 20822397
TI  - Pharmacological basis for the medicinal use of Holarrhena antidysenterica in gut
      motility disorders.
AB  - CONTEXT: Holarrhena antidysenterica Wall. (Apocynaceae) is widely used in
      traditional medical system for treatment of constipation, colic, and diarrhea.
      AIM: This study was carried out to provide pharmacological basis for medicinal
      use of Holarrhena antidysenterica in gastrointestinal disorders. MATERIALS AND
      METHODS: Hydro-ethanolic crude extract of Holarrhena antidysenterica (HaCE) and
      its fractions were studied in various gastrointestinal isolated tissue
      preparations. RESULTS: In guinea pig ileum tissues, HaCE at 0.3-10 mg/mL caused
      pyrilamine-sensitive spasmogenic effect. When tested in spontaneously contracting
      rabbit jejunum preparations, HaCE (0.01-3.0 mg/mL) caused moderate stimulation,
      followed by a relaxant effect at next higher concentrations. In presence of
      pyrilamine, the contractile effect was blocked and the relaxation was observed at
      lower concentrations (0.01-0.3 mg/mL). HaCE inhibited the high K(+) (80 mM)
      induced contractions at concentration range of 0.01-1.0 mg/mL and shifted Ca(++)
      concentration response curves to the right, like that caused by verapamil.
      Activity-directed fractionation revealed that the spasmogenic component was
      concentrated in the aqueous fraction, while the spasmolytic component was
      concentrated in the organic fraction. DISCUSSION AND CONCLUSION: These results
      indicate that the gut stimulant and relaxant activities of Holarrhena
      antidysenterica are mediated possibly through activation of histamine receptors
      and Ca(++) channel blockade, respectively and this study provides sound
      mechanistic background for its usefulness in gut motility disorders such as
      constipation, colic, and possibly diarrhea.

PMID- 20822398
TI  - Colonization to aquifers and adaptations to subterranean interstitial life by a
      water beetle clade (Noteridae) with description of a new Phreatodytes species.
AB  - Due to its tectonically uplifted, mountainous landscape and copious rainfall, the
      Japanese archipelago possesses plentiful, persistent groundwater in alluvial
      plains. However, Phreatodytes, an endemic water beetle genus found in
      groundwater, is now critically endangered due to the devastation of subterranean
      water ecosystems. Phreatodytes beetles were collected from driven wells near the
      Ooi River estuary in central Japan. The beetles were distinguished from all
      described species by their thoracic and genital morphologies, and described as a
      new species, Phreatodytes haibaraensis. The unique habitat of this species is the
      hyporheic zone of a gravelly riverbed in an estuary, and the habitat represents
      the eastern limit of the known distribution range of the genus. Molecular
      phylogenetic analysis based on mitochondrial and nuclear gene sequences revealed
      that Phreatodytes is a member of the Noteridae and forms a clade with Notomicrus.
      This suggests that the genus colonized the hyporheic zone from surface waters,
      and that it adapted to subterranean interstitial life by becoming minute and
      slender, by losing its eyes, pigmentation, as well as its ability to fly and
      swim, and by developing a permanent underwater life cycle, and erect hairlike
      setae on the thorax and elytra. In addition to the beetle, several stygobiontic
      species, including mollusks and fishes, were found in pumped groundwater. These
      results suggest that the gravelly riverbed of a rapid river estuary in Central
      Japan harbors biodiverse, locally differentiated hyporheic organisms comprising a
      unique subterranean interstitial ecosystem.

PMID- 20822399
TI  - Population structure of Aegialites beetles (Coleoptera, Salpingidae) on the
      coasts of Hokkaido, northern Japan.
AB  - We conducted a molecular phylogeographic analysis of Aegialites beetles sampled
      on the coasts of Hokkaido, northern Japan, using a partial sequence (553 bp) of
      the mitochondrial ND2 gene. The beetles are flightless and are adapted to the
      supralittoral zone of rocky shores. In all, 249 individuals from 17 populations
      were included in the molecular analysis. Haplotypes of the Aegialites beetles
      studied comprised two distinct lineages with different distributional ranges: one
      (lineage A) on the coasts of Hokkaido facing the Sea of Japan and the Sea of
      Okhotsk, and the other (lineage B) mostly on the Pacific coast and on the
      Shiretoko Peninsula in northeastern Hokkaido. These haplotype lineages clearly
      indicate two groups of populations, one comprising lineage A haplotypes (group A)
      and the other lineage B haplotypes (group B). Only one population, at Taisei
      facing the Sea of Japan on the Oshima Peninsula, contained a mixture of
      haplotypes from the two lineages. Genetic divergence among populations was larger
      in group B than in group A. Despite the unidimensional nature of the beetles'
      habitat, no correlation was found between the degree of genetic differentiation
      and geographic distance in either group of populations. Population genetic
      parameters suggested that the two lineages originated in the Pliocene, and that
      the populations in group A underwent a rapid increase in population size, whereas
      those in group B did not. We present a scenario for the allopatric divergence of
      the two lineages.

PMID- 20822400
TI  - Epizoanthus spp. associations revealed using DNA markers: a case study from
      Kochi, Japan.
AB  - Zoanthids (Cnidaria, Hexacorallia) of the genus Epizoanthus are often found in
      association with other marine invertebrates, including gastropods and hermit
      crabs. However, little information exists on the specificity and nature of these
      associations due to a lack of investigation into Epizoanthus species diversity,
      and the taxonomy of Epizoanthus is therefore confused. In this study, analyses of
      morphological data (tentacle number, polyp size, etc) and molecular data
      (mitochondrial cytochrome oxidase subunit 1 = COI, 16S ribosomal DNA = 16S rDNA)
      were used to examine Epizoanthus specimens from Tosa Bay, Kochi, Japan. The
      Epizoanthus specimens were found on both live gastropods (Gemmula unedo) and
      hermit crabs (Paguristes palythophilus) inhabiting G. unedo and G. cosmoi shells.
      While morphological analyses did not show clear differences between examined
      specimens, both COI and mt 16S rDNA clearly divided the specimens into two
      groups, one associated only with hermit crabs (= Epizoanthus sp. C), and another
      associated only with living gastropods (= Epizoanthus sp. S). Unexpectedly, DNA
      sequences from both groups did not match with two previously reported Epizoanthus
      species from Japan (E. indicus, E. ramosus), indicating they both may be
      undescribed species. These results highlight the utility of DNA "barcoding" of
      unknown zoanthids, and will provide a foundation for re-examinations of
      Epizoanthus species diversity and specificity, which will be critical in
      understanding the evolution of these unique marine invertebrates.

PMID- 20822401
TI  - Comparison of the life cycle and photoperiodic response between northern and
      southern populations of the terrestrial slug Lehmannia valentiana in Japan.
AB  - The terrestrial slug Lehmannia valentiana was first recorded in Japan in the late
      1950s and is now distributed throughout the country. Previous studies have
      revealed that in Osaka, southwestern Japan, L. valentiana reproduces from
      November to April. In the present study, in order to clarify the climatic
      adaptations of L. valentiana in Japan, we examined the life cycle of this slug in
      Sapporo, northern Japan. In the Sapporo population, the ratio of gonad weight to
      body weight reached a maximum in September. Most slugs had mature sperm from late
      August to April and large oocytes from September to April. Thus, the Sapporo
      population of L. valentiana commenced reproduction two months earlier than the
      Osaka population. We also examined the effect of various photoperiodic conditions
      on growth and reproductive maturation in both the Osaka and Sapporo populations.
      The effect of photoperiod on growth was different in the two populations. In both
      populations, however, reproductive maturation was induced by short days of
      photophase 14 h or less, and there was no obvious difference between the two
      populations, even though reproductive maturation in the wild commences in
      different seasons. This indicates the possibility that L. valentiana adapts to
      climatically different regions without changes in its critical daylength in
      photoperiodic response.

PMID- 20822402
TI  - Apoptosis and autophagy in the midgut epithelium of Acheta domesticus (Insecta,
      Orthoptera, Gryllidae).
AB  - The midgut epithelium of Acheta domesticus (Insecta, Orthoptera, Gryllidae),
      which is composed of columnar digestive cells and regenerative crypts,
      degenerates in two manners: necrotic and apoptotic. While necrosis was described
      in our previous paper, programmed cell death was the aim of the present studies.
      The first morphological signs of programmed cell death in midgut epithelium cells
      are alterations in the cytoplasm connected with shrinkage of the cells. Gradual
      modifications in a cell's structure cause it to be discharged into the midgut
      lumen, where it disintegrates. Autophagy is involved in the disintegration of
      organelles. The transitions of apoptotic cells are described at the
      ultrastructural level. Immunostaining methods were used in order to indicate the
      early stages of apoptosis when DNA fragmentation, which results from apoptotic
      signaling cascades, occurs.

PMID- 20822403
TI  - The influence of Pleistocene refugia on the evolutionary history of the Japanese
      hare, Lepus brachyurus.
AB  - We performed a phylogeographic analysis of the Japanese hare, Lepus brachyurus,
      using the mitochondrial cytochrome b gene (1140 bp). In total, 119 haplotypes
      were recovered from 197 samples isolated from 82 localities on three main islands
      of the Japanese archipelago: Honshu, Sikoku, Kyushu, Sado Island and the Oki
      Islands. Results showed two distinct clades at a genetic distance of 3.5%,
      equivalent to an estimated 1.2 million years. The two clades, encompassing seven
      subclades, showed an apparent geographic affinity to Kyushu, Shikoku and the
      nearby area of Honshu (southern group) by one clade, whereas the other clade
      covered the remaining area of Honshu (northern group). The landscape shape
      interpolation analysis exhibited a higher genetic diversity in the southern parts
      of central Honshu (northern group) and Shikoku and Kyushu regions (southern
      group), suggesting the existence of multiple geographical origins of population
      expansion in each clade. The Bayesian skyline plot analysis showed that lineage
      diversifications occurred about 0.35, 0.20 and 0.05 million years ago (Mya),
      which coincide closely with the glacial-interglacial cycles during the
      Pleistocene. Therefore, we suggest that the Japanese hare population once
      inhabited northern and southern refugia, and subsequently developed several
      populations through local demographic fluctuations. The present day demarcation
      in the northern and southern geographic groups is considered to be a temporal
      remnant of Pleistocene population dynamics and the geographic boundary between
      them could move or fade away in time.

PMID- 20822405
TI  - A new in vitro ovulation model for medaka based on whole ovary culture.
AB  - We sought to establish a new in vitro ovulation model using the whole ovaries of
      the medaka. Ovaries of the fish, which had been acclimated to the usual
      reproductive conditions (26 degrees C, 14 h light/10 h dark) and which had then
      been kept at least one day at 30 degrees C, were isolated 2 h before the expected
      in vivo ovulation time. When the ovaries were cultured in 90% medium 199 solution
      at 30 degrees C or 36 degrees C, oocytes were liberated with a gradual increase
      in the ovulation rate at 2 to 5 h of ovulation time. The maximum ovulation rate
      was approximately 45%. Ovulated oocytes were fertilized and subsequently
      developed into adults. In vitro ovulation of medaka ovaries was inhibited by the
      addition of metalloproteinase inhibitors to the culture. In this in vitro
      ovulation model, the holes formed on the follicle layer upon follicle rupture at
      ovulation were sealed, strongly suggesting the importance of the germinal
      epithelium in the process. The present study indicates that our new in vitro
      ovulation model is useful for investigating the role of germinal epithelial cells
      in the ovulate process of the medaka fish.

PMID- 20822404
TI  - Subcellular localization of Tektin2 in rat sperm flagellum.
AB  - Tektins are evolutionarily conserved filament-forming proteins localized in
      flagella and cilia, and have been reported to be involved in the stability and
      structural complexity of axonemal microtubules. Five mammalian Tektins (Tektin1
      5) have been reported. Of these, Tektin2 (TEKT2) has been found to be required
      for normal flagellum structure and function. Tekt2-null sperm display flagellum
      bending and reduced motility, probably due to disruption of the dynein inner arm.
      However, the subcellular localization of TEKT2 in spermatozoa has not been
      clarified at the ultrastructural level. To elucidate the molecular localization
      of TEKT2 in flagella of rat spermatozoa, we performed confocal laser scanning
      microscopy, extraction of flagella followed by immunoblot analysis, and
      immunogold electron microscopy. Extraction of sperm flagella by SDS-EDTA resulted
      in complete extraction of axonemal tubulins, while TEKT2 was only partially
      released from flagella, suggesting that TEKT2 might be present in the peri
      axonemal component, not directly associated with axonemal tubulins. Confocal
      laser scanning microscopy and pre-embedding immunoelectron microscopy revealed
      that TEKT2 is associated with the surface of outer dense fibers (ODFs). TEKT2 may
      function as an ODF-affiliated molecule required for flagellum stability and sperm
      motility.

PMID- 20822406
TI  - Limnodrilus simplex sp. nov. (Oligochaeta: Naididae: Tubificinae) from Changjiang
      River, China.
AB  - Limnodrilus simplex sp. nov. (Oligochaeta: Naididae: Tubificinae) is described
      based on a single specimen from the mainstream of the Changjiang River near
      Anqing City, Anhui Province, China. The new species is assigned to Limnodrilus by
      the presence of long vasa deferentia, spindle-shaped atria with long ejaculatory
      ducts, large prostate glands, and thick cylindrical penial sheaths. It differs
      from its congeners in having simple-pointed chaetae and cuticularized penial
      sheaths without hoods. Limnodrilus simplex is closer to L. paramblysetus and L.
      amblysetus in possessing penial sheaths with relatively low length/maximum width
      ratio.

PMID- 20822407
TI  - A review of the leafhopper genus Hishimonoides Ishihara (Hemiptera: Cicadellidae:
      Deltocephalinae).
AB  - Here, we review the species of the Old World leafhopper genus Hishimonoides
      lshihara. Twelve species, including two new species, are recognized in the genus:
      H. arbudae Viraktamath et al. (India), H. aurifascialis Kuoh (China), H.
      bougainvilleae Viraktamath et al. (India, China), H. chinensis Anufriev (China),
      H. curvatus sp. nov. (China: Guangxi), H. dentimarginus Li and Zhang (China), H.
      miaolingensis Li and Zhang (China), H. orientalis Mahmood (Bangladesh, India), H.
      recurvatis Li (China), H. sellatiformis lshihara (China, Japan), H. spinosus
      Viraktamath et al. (India) and H. similis sp. nov. (China: Zhejiang, Gansu,
      Hunan). The type species and all known species from China are redescribed. One
      new synonym is revealed, Hishimonoides laterosporeus Li and Zhang, 2005 , a
      junior synonym of Hishimonoides chinensis Anufriev, 1970 . A key to the species
      in this genus is given, and their genital structures are illustrated.

PMID- 20822415
TI  - Verification of clipless closure of cystic duct by harmonic scalpel.
AB  - INTRODUCTION: The excellent results of harmonic scalpel (HS) for closure of blood
      vessels encouraged surgeons to use these instruments for cystic ducts. The use of
      HS on tissues other than blood vessels was started with little data about its
      efficacy or safety. Therefore, this study was designed to verify the safety and
      efficacy of HS for achieving safe closure of the cystic ducts after laparoscopic
      cholecystectomy. MATERIALS AND METHODS: Sixty patients with symptomatic gallstone
      disease were enrolled in this prospective case control study. The patients were
      operated with laparoscopic technic and divided into two groups (n = 30). After
      the dissection of Calot's triangle, proximal cystic ducts on common bile ducts
      were sealed with single surgical clips (SC) in both groups. In the first group,
      distal of the cystic ducts was sealed with single SC and the gallbladders were
      removed with SC. In the second group, distal of the cystic ducts was sealed with
      HS and the gallbladders were removed as sealed cystic ducts with HS. Twenty-gauge
      catheters were inserted into the fundus of gallbladders in vitro and connected to
      the arterial line transducer set. A gradually increasing pressure was applied
      through a sphygmomanometer. The bursting pressures of the gallbladders were
      measured, and differences between HS and single SC groups were calculated with
      independent samples t-test. The value of P < 0.05 was accepted as significant.
      RESULTS: The mean cystic duct bursting pressures in single SC and HS groups were
      332.46 +/- 4.62 and 343.06 +/-4.28 mmHg, respectively. The mean values between
      the groups were found significant and indicated the superior results of HS.
      CONCLUSIONS: HS sealer could be an alternative method for cystic duct closure,
      especially for avoiding the clip displacement and migration of the clip. Results
      of this study indicated that HS sealer was as reliable as single SC and it could
      be accepted as a standard closure technic.

PMID- 20822416
TI  - Removal of long, complex foreign bodies from bladder using single laparoscopic
      port under pneumovesicum.
AB  - Whereas the majority of foreign bodies are managed endoscopically, complex
      objects, or those associated with significant injury, may require open removal.
      However, with the advent of newer, minimally invasive techniques, these objects
      can be successfully removed by using laparoscopic instruments. In this article,
      we describe our experience of using a single 5-mm laparoscopic port under
      pneumovesicum for removal of a knotted electric wire measuring 149 cm in length,
      with minimal invasiveness and avoidance of urethral injury. Using a cystoscope as
      the optical device through the urethra, a port can be introduced suprapubically.
      After insufflations of carbon dioxide at 12 mm Hg, the knotted electric cables
      were fragmented into several parts by laparoscopic scissor, then these parts were
      removed one by one. The optimal removal technique is dictated primarily by the
      nature of the foreign body. This case presents the feasibility of the
      pneumovesicum method in using a single laparoscopic port in cases of long,
      complex objects in the adult bladder.

PMID- 20822417
TI  - Partial amniotic carbon dioxide insufflation during minimally invasive fetoscopic
      interventions seems safe for the fetal brain in sheep.
AB  - BACKGROUND: Partial amniotic carbon dioxide insufflation (PACI) during fetoscopic
      interventions greatly improves visualization of intraamniotic contents. The
      purpose of this study was to assess any histologically discernable effects from
      this approach on the fetal brain after long-term survival in sheep. METHODS: Six
      pregnant ewes between 63 and 92 days of gestation underwent PACI after fetoscopic
      intraamniotic access. Insufflation pressures ranged between 7 and 15 mm Hg (mean
      11.7; median 12.5). Insufflation times ranged between 45 and 80 minutes (mean
      55.8 minutes; median 52.5) and depended on the duration of various percutaneous
      fetoscopic maneuvers (e.g., posturing, fetal transesophageal electrocardiography,
      and chronic fetal vascular access) that were tested during these studies. After
      fetal spontaneous delivery between 147 and 150 days of gestation, 5 of the lambs
      were observed for abnormal neurological symptoms. The last ewe and her sheep were
      terminated at 133 days of gestation for humane reasons. All six brains were
      examined for hemorrhage, embolism, infarctions, inflammatory changes, and
      abnormal cortical maturation. An unoperated sibling was available as a control.
      RESULTS: The 5 sheep that were spontaneously delivered exhibited no abnormal
      neurological findings. In all 6 sheep, PACI did not result in any histologically
      discernable damage to their brain in these long-term studies. Maternal and fetal
      complications were not observed during or after the approach. CONCLUSION: The
      application of PACI during minimally invasive fetoscopic interventions seems safe
      for the fetal brain. Due to the still limited clinical experience with PACI,
      continued assessment of its maternal and fetal risks as well as management are
      required.

PMID- 20822418
TI  - Open versus laparoscopic treatment for pan-peritonitis secondary to perforated
      appendicitis in children: a prospective analysis.
AB  - PURPOSE: Reports on laparoscopic treatment (LT) of peritonitis secondary to
      perforated appendicitis (PA) in children often include localized
      peritonitis/appendiceal mass, without specifically referring to pan-peritonitis
      (PP). This study compared LT with open treatment (OT) in only those patients with
      PP secondary to PA. METHODS: PP was defined as generalized abdominal rigidity on
      presentation with purulent material intraoperatively found throughout the entire
      abdominal cavity. Based on this definition, we identified 23 cases of PP
      secondary to PA from all our cases of appendicitis from 2004 to 2008 and
      prospectively collected data. RESULTS: Surgical intervention was LT in 12 cases
      and OT in 11 cases. Appendectomy was successful in all cases without
      intraoperative complications. Mean age at surgery, sex ratio, preoperative mean
      white blood cell count, and C-reactive protein were similar. Mean operative time
      was 119 minutes for LT and 107 minutes for OT (P = NS). Mean volume of saline
      used for peritoneal lavage was 2730 mL for LT and 2950 mL for OT (P = NS).
      Duration of analgesic usage was significantly shorter in LT (P = 0.01).
      Postoperative wound infections were significantly less in LT (P = 0.04: LT 0, OT
      4/11). Adhesive bowel obstruction occurred in one LT case and three OT cases (P =
      NS); none required surgery. There were two cases of intraabdominal abscess in
      each group, all were conservatively treated. Time taken to become afebrile, for
      white blood cell count and C-reactive protein to normalize, for intravenous
      antibiotics to be ceased, and for oral feeding to be commenced were not
      significantly different. Mean hospitalization was significantly shorter for LT (P
      = 0.04). CONCLUSIONS: LT would appear to be superior for the treatment of PP
      secondary to appendicitis in children and would even seriously consider it as the
      procedure of choice.

PMID- 20822419
TI  - Outcomes of laparoscopic and open total colectomy in the pediatric population.
AB  - INTRODUCTION: Total colectomy, performed either with proctecomy and ileal pouch
      anal anastomosis or with ileorectostomy, is standard for pediatric patients with
      ulcerative colitis or familial adenomatous polyposis syndrome, respectively. The
      complication rates from adult series have been reported to be as high as 40%-50%.
      We audited our experience to define the complication rates in children and
      determine whether the use of laparoscopy has the potential to lessen the number
      or change the type of complications. METHODS: We conducted a retrospective review
      of all pediatric patients who underwent total colectomy with either proctectomy
      with ileal pouch anal anastomosis or with ileorectostomy at a single institution
      from 1998 to 2008. Data are expressed as mean +/- standard deviation. Continuous
      variables were analyzed using a Student's t-test; and discrete variables were
      analyzed using a Fisher's exact test, where appropriate. Significance was set as
      P < or = 0.05. RESULTS: Forty-four patients aged 58 days to 18 years (mean 11.7
      +/- 5.3 years) underwent total colectomy from 1998 to 2008. The indications for
      surgery were ulcerative colitis (27), familial adenomatous polyposis syndrome
      (11), total colonic Hirschprungs (2), and others (3). Follow-up was significantly
      greater in the open group (2.8 years) than in the laparoscopic group (1.1 years,
      P = 0.02). Nineteen patients (43%) suffered major complications (other than
      pouchitis). There was 1 anastomotic leak. There were no statistically significant
      differences found between the laparoscopic and open approaches with regard to
      postoperative small bowel obstruction, postoperative abdominal or pelvic abscess,
      anal stricture requiring dilation, wound infection, other complications, or time
      to complication. Patients who underwent laparoscopic ileal pouch anal anastomosis
      had one occurrence of pouchitis (1/10) compared with 19/34 in the open group (P =
      0.03). CONCLUSIONS: This series demonstrates that laparopscopic colectomy yields
      similar outcomes as the traditional open method, both in type and severity of
      complications. Patients who had an ileal pouch created through the laparoscopic
      approach had fewer occurrences of pouchitis.

PMID- 20822420
TI  - Outcome after laparoscopic fundoplication in children under 1 year.
AB  - BACKGROUND: Laparoscopic fundoplication has not been extensively reviewed to
      establish the efficacy and outcome in infants. Our aims were to investigate the
      outcome of laparoscopic fundoplication in infants and assess factors predicting
      outcome. METHODS: We performed a retrospective study on infants undergoing
      laparoscopic fundoplication. Demographic data, operating time, length of hospital
      stay, complications, and need for redo fundoplication were recorded. Chi-squared
      test was performed to correlate symptoms and outcome. There were 79 patients.
      Median age was 6 months (range 0.5 to 11) and weight was 5.6 kg (2.6 to 10).
      Forty-eight were neurologically impaired, 4 had esophageal atresia and tracheo
      esophageal fistula. RESULTS: The most common presenting symptoms were vomiting
      (71), failure to thrive (63), recurrent aspiration (47), and acute life
      threatening events (35). Thirty-six had severe, 20 moderate, and 19 mild reflux.
      Three intraoperative complications occurred: 2 (2.5%) conversions (liver bleed,
      inability to tolerate pneumoperitoneum) and 1 pneumothorax. Median time to full
      feeds was 4 days (interquartile range 3 to 6) and discharge 6 days (4 to 16).
      Thirty-one patients had late complications. Nineteen had retching; 2 had
      dysphagia-needing dilatation. Sixteen patients (20%) had late mortality due to co
      morbidities. Fourteen (18%) needed redo fundoplication. There was no correlation
      between weight, severity of reflux, presence of either ATLE, or neurological
      impairment and the incidence of recurrence. CONCLUSIONS: Laparoscopic
      fundoplication can be safely performed in infants. There was no predictor of
      recurrence. However, there is a 20% late mortality in patients with severe co
      morbidities, which needs to be taken into account when counseling patients.

PMID- 20822421
TI  - Laparoscopic Nissen fundoplication versus Thal fundoplication in children:
      comparison of short-term outcomes.
AB  - BACKGROUND: The aim of this study was to compare short-term outcomes, including
      intra- and perioperative complications following laparoscopic Nissen versus Thal
      fundoplication. PATIENTS AND METHODS: From July 1998 until April 2007, 175
      patients were recruited. Patients were prospectively randomized to either a
      Nissen wrap or a Thal wrap. Observation period was 6 weeks after surgery.
      RESULTS: 89 Nissen and 86 Thal were performed. The mean age at the time of
      operation (OP) was 5.2 years. Demographics were similar, although weight at OP
      was significantly less in the Nissen group. Intraoperative complications during a
      Nissen included bleeding from a liver laceration in 2 patients (1 required
      conversion) and small bowel perforation during open port insertion in 1 patient.
      There were two conversions in the Thal group, due to bleeding from the omentum in
      1 patient and equipment failure in the other. In a third patient the colon was
      perforated during insertion of percutaneous endoscopic gastrostomy (PEG) and
      repaired laparoscopically. Post-OP dysphagia was similarly distributed among both
      groups, but was significantly more severe after a Nissen (P = 0.018). There were
      two early deaths: in the Nissen group, 1 child died from peritonitis after the
      gastrostomy tube fell out, whereas one death in the Thal group was caused by
      respiratory failure associated with the patient's underlying condition.
      CONCLUSIONS: There was no statistical difference in the short-term outcomes
      between laparoscopic Nissen and Thal fundoplication, apart from a higher rate of
      esophagoscopy for severe dysphagia in the Nissen group. The higher number of
      postoperative complications in the Nissen group was largely due to gastrostomy
      related problems.

PMID- 20822422
TI  - Morphological and molecular analyses of host and nonhost interactions involving
      barley and wheat and the covered smut pathogen Ustilago hordei.
AB  - Ustilago hordei interactions on coleoptiles of barley host cultivars Odessa
      (compatible), Hannchen (incompatible, carrying the Ruh1 resistance gene), and on
      nonhost Neepawa wheat were studied using light and fluorescent microscopy.
      Autofluorescence, mainly caused by callose accumulation, was more rapidly
      expressed in nonhost wheat at 30 to 72 h compared with the incompatible reaction
      between 72 and 144 h. Microarray results demonstrated that more than half of the
      893 differentially regulated genes were observed in Neepawa; of these genes, 45%
      fell into the defense- and stress-related classes in Neepawa compared with 25 and
      37% in Odessa and Hannchen, respectively. Their expression coincided with the
      early morphological defense responses observed and were associated with the
      jasmonic acid and ethylene (JA/ET) signaling pathway. Expression patterns in
      Odessa and Hannchen were similar, involving fewer genes and coinciding with later
      morphological defense responses of these varieties. Although no visible
      hypersensitive response was apparent in Hannchen or Neepawa, specific
      upregulation of hypersensitivity-related proteins was observed, such as beta-VPE
      at 48 h. Expression levels of the callose synthase gene were closely associated
      with callose accumulation. Differential responses in defense-gene expression
      among disease reaction types included upregulation of PR-1.1b and downregulation
      of a nonspecific lipid transfer protein in the incompatible and compatible
      interactions, respectively. Transcript levels of EDS1 and PAD4, involved in both
      basal resistance and R-mediated resistance to avirulent pathogens, were up
      regulated during both nonhost and Ruh1-mediated resistance. Application of methyl
      jasmonate, salicylic acid and ET to leaves revealed that only PR1.1b is strongly
      up-regulated by all three compounds, while the majority of the defense-related
      genes are only slightly up-regulated by these signaling compounds.

PMID- 20822423
TI  - Biological activity of the Agrobacterium rhizogenes-derived trolC gene of
      Nicotiana tabacum and its functional relation to other plast genes.
AB  - Agrobacterium rhizogenes induces hairy roots through the activity of three
      essential T-DNA genes, rolA, rolB, and rolC, whereas the orf13 gene acts as an
      accessory root-inducing gene. rolB, rolC, and orf13 belong to the highly diverged
      plast gene family with remotely related representatives in the endomycorrhizal
      basidiomycete Laccaria bicolor. Nicotiana glauca and N. tabacum contain A.
      rhizogenes-derived T-DNAs with active plast genes. Here, we report on the
      properties of a rolC homolog in N. tabacum, trolC. Dexamethasone-inducible trolC
      and A4-rolC genes from A. rhizogenes A4 induce comparable, strong growth effects
      affecting all parts of the plants. Several have not been described earlier and
      were found to be very similar to the effects of the distantly related plast gene
      6b. They include leaf chlorosis and starch accumulation, enations, increase of
      sucrose-dependent leaf disk expansion, growth of isolated roots on low-sucrose
      media, and stimulation of sucrose uptake by small root fragments. Collectively,
      our findings indicate that enhancement of sucrose uptake plays an important role
      in generating the complex 6b and rolC phenotypes and might be an ancestral
      property of the plast genes.

PMID- 20822424
TI  - High uric acid level during the first 20 weeks of pregnancy is associated with
      higher risk for gestational diabetes mellitus and mild preeclampsia.
AB  - OBJECTIVE: To examine the association between uric acid (UA) level during the
      first 20 weeks of pregnancy and the development of gestational diabetes mellitus
      (GDM) and preeclampsia in the second half of pregnancy. METHODS: The study
      population included registered births (n = 5507) between 2001 and 2007 in a
      tertiary medical center. The UA levels during the first 20 weeks of pregnancy
      were sorted by UA <= 2.4 mEq/L; UA = 2.5-4.0 mEq/L, UA = 4.1-5.5 mEq/L, and UA >
      5.5 mEq/L. The linear-by-linear chi-square test and ROC curves were used to
      determine the association between UA level during the first 20 weeks and
      pregnancy complications. Multivariate analyses were performed to demonstrate
      whether UA level is an independent factor for the prevalence of preeclampsia and
      GDM. RESULTS: Significant linear association was documented between UA level in
      the first 20 weeks and the prevalence of GDM and mild preeclampsia. The lowest
      and the highest prevalence of GDM were found in the UA <= 2.4 mEq/L group (6.3%)
      and in the UA > 5.5 mEq/L group (10.5%) (p < 0.001), respectively. Mild
      preeclampsia was diagnosed in 2.1% of the patients from the UA <= 2.4 mEq/L
      group, 3.3% from the UA = 2.5-4.0 mEq/L group, 5.3% from the UA = 4.1-5.5 mEq/L
      group, and 4.5% from the UA > 5.5 mEq/L group (p < 0.001). Three multiple
      logistic regression models controlling for maternal age showed that UA level is
      an independent risk factor for both GDM and mild preeclampsia. CONCLUSIONS: UA
      levels in the highest quartile of the normal range during the first 20 weeks of
      pregnancy are associated with higher risk for the development of GDM and mild
      preeclampsia.

PMID- 20822425
TI  - HELLP syndrome: 8 years of experience from a tertiary referral center in western
      Turkey.
AB  - OBJECTIVE: This study was performed to determine the incidence, symptomatology,
      complications, mode of delivery, treatment modalities, and risk factors for
      maternal outcome and perinatal outcome in women with HELLP syndrome. METHODS: A
      total of 303 pregnancies with hemolysis, elevated liver enzymes, and low platelet
      count (HELLP) syndrome diagnosed antenatally were reviewed between 2002 and 2009.
      Demographic data, including age, parity, gestational age, and clinical and
      laboratory findings, were recorded from the medical files. In addition, delivery
      route, indication of cesarean section, and fetal and maternal complications were
      determined. RESULTS: Acute renal failure (20.5%) was the most common
      complication. Eclampsia was present in 303 women with HELLP syndrome (52%). There
      were four maternal deaths (1.4%). The perinatal mortality rate was 20.3%. The
      percentages of intracerebral hemorrhage and maternal death were higher in women
      with eclampsia than in those without (6.3% vs. 0.8%, p = 0.01 and 4.8% vs. 0.4%,
      p = 0.02, respectively). A nadir platelet count of <=50,000 cells/mm(3), a peak
      serum AST of >150 IU/L, and a peak serum LDH of >=1400 IU/L were not independent
      risk factors of an adverse outcome. CONCLUSION: We concluded that the incidence
      rates of serious maternal and fetal morbidities and mortalities are increased in
      HELLP syndrome. Laboratory parameters of HELLP syndrome are not independent risk
      factors for adverse neonatal-maternal outcome. Adequate and prompt diagnosis and
      management are crucial in patients with HELLP syndrome.

PMID- 20822426
TI  - Risk indicators for eclampsia in gestational hypertension or mild preeclampsia at
      term.
AB  - OBJECTIVE: To evaluate whether eclampsia can be predicted in gestational
      hypertension or mild preeclampsia at term. METHODS: For this case-control study
      we selected 76 cases with eclampsia from the LEMMoN study and 1149 controls with
      mild hypertensive disease of pregnancy, who did not develop eclampsia, from the
      HYPITAT study. Risk indicators for eclampsia, identified in multivariable
      logistic regression, were used to assess the predictive capacity of our model
      with receiver-operating characteristic (ROC) curve analysis. Model optimism was
      assessed with bootstrapping. RESULTS: Maternal age, non-Caucasian ethnicity,
      systolic blood pressure >155 mmHg, >=2+ protein on dipstick, elevated uric acid,
      creatinin >74 MUmol/L, aspartate aminotransferase >30 U/L, and lactate
      dehydrogenase >400 U/L were significantly associated with eclampsia. Other
      factors included in the model were previous fetal loss, previous miscarriage,
      gestational age, and low platelet count. The area under the ROC curve was 0.92.
      Bootstrapping showed minimal overfitting of the model. CONCLUSION: In women with
      gestational hypertension or mild preeclampsia at term eclampsia can be predicted.

PMID- 20822427
TI  - Impedance cardiography facilitates differentiation of severe and superimposed
      preeclampsia from other hypertensive disorders.
AB  - OBJECTIVE: To determine if hemodynamic profiling using noninvasive impedance
      cardiography (ICG) reliably identifies the patient with severe (SPRE) or
      superimposed (SuPRE) preeclampsia. METHODS: Late gestation hypertensive pregnant
      patients underwent immediate ICG evaluation. Findings were compared between
      patients subsequently achieving or not achieving American College of
      Obstetricians and Gynecologists criteria for SPRE or SuPRE. RESULTS: Patients
      with severe disease were more likely to have depressed cardiac function and
      higher systolic blood pressure, mean arterial blood pressure, systemic vascular
      resistance, and thoracic fluid content compared to nonsevere hypertensive
      disease. CONCLUSION: ICG hemodynamic profiling of late gestation hypertensive
      patients can rapidly and reliably identify those with SPRE or SuPRE.

PMID- 20822428
TI  - Combined vitamin C and E supplementation for preeclampsia: no significant effect
      but significant heterogeneity?

PMID- 20822429
TI  - The concentrations of markers of bone turnover in normal pregnancy and
      preeclampsia.
AB  - BACKGROUND: The purpose of our study was to investigate the concentrations of
      markers of bone turnover in normal pregnancy and preeclampsia. MATERIAL AND
      METHODS: Forty-five pregnant patients with preeclampsia, 78 healthy pregnant
      women (26 in first, 26 in the second, and 26 in third trimester of pregnancy),
      and 20 nonpregnant women were included in the study. Serum concentrations of
      osteoprotegrin (OPG), receptor activator of nuclear factor kappa B ligand
      (sRANKL), and the markers of bone turnover, osteocalcin and CrossLaps-degradation
      products of type I collagen, were determined using the ELISA method. Statistical
      analysis was performed using Mann-Whitney U-test. RESULTS: The concentrations of
      sRANKL and OPG were significantly higher in the second trimester of normal
      pregnancy when compared to the first and the third trimesters and to nonpregnant
      controls. The concentrations of osteocalcin were significantly higher in the
      first trimester of physiological pregnancy in comparison with nonpregnant women
      and with second and third trimesters of pregnancy. The concentrations of
      CrossLaps were significantly higher in the second trimester of normal pregnancy
      when compared to the first and third trimester. In preeclampsia, the sera
      concentrations of osteocalcin and CrossLaps were significantly higher when
      compared to the third trimester of normal pregnancy. CONCLUSION: The results
      suggest that the bone formation is increased in the first trimester, whereas the
      bone resorption is increased in the second trimester of normal pregnancy.
      Furthermore, the results suggest that the bone turnover is increased in patients
      with preeclampsia when compared to healthy normotensive pregnant women.

PMID- 20822430
TI  - Effect of Meloidogyne incognita inoculum density and application rate of
      Paecilomyces lilacinus strain 251 on biocontrol efficacy and colonization of egg
      masses analyzed by real-time quantitative PCR.
AB  - The fungal biocontrol agent, Paecilomyces lilacinus strain 251 (PL251), was
      evaluated for its potential to control the root-knot nematode Meloidogyne
      incognita on tomato at varying application rates and inoculum densities.
      Conversely to previous studies, significant dose-response relationships could not
      be established. However, we demonstrated that a preplanting soil treatment with
      the lowest dose of commercially formulated PL251 (2 * 10(5) CFU/g soil) was
      already sufficient to reduce root galling by 45% and number of egg masses by 69%
      when averaged over inoculum densities of 100 to 1,600 eggs and infective
      juveniles per 100 cm(3) of soil. To determine the role of colonization of M.
      incognita egg masses by PL251 for biocontrol efficacy, a real-time quantitative
      polymerase chain reaction (PCR) assay with a detection limit of 10 CFU/egg mass
      was used. Real-time PCR revealed a significant relationship between egg mass
      colonization by PL251 and the dose of product applied to soil but no correlation
      was found between fungal density and biocontrol efficacy or nematode inoculum
      level. These results demonstrate that rhizosphere competence is not the key mode
      of action for PL251 in controlling M. incognita on tomato.

PMID- 20822431
TI  - Comparison of soil fungal community structure in different peanut rotation
      sequences using ribosomal intergenic spacer analysis in relation to aflatoxin
      producing fungi.
AB  - The present study focuses on determining soil fungal community structure in
      different peanut-cropping sequences by using a high-resolution DNA fingerprinting
      technique: ribosomal intergenic spacer analysis (RISA). This study was initiated
      to determine fungal community profiles in four peanut-cropping sequences
      (continuous peanut, 4 years of continuous bahiagrass followed by peanut, peanut
      corn-cotton, and peanut-cotton rotations), with a special focus to evaluate
      whether the profiles under investigation may have also indicated microbial
      differences that could affect Aspergillus flavus populations. Results indicated
      75% similarities among fungal communities from the same cropping sequences as
      well as with similar times of sampling. Polymerase chain reaction (PCR)-based
      detection of A. flavus directly from these soils was carried out using A. flavus
      specific primers (FLA1 and FLA2) and also through quantitative estimation on A.
      flavus and A. parasiticus agar medium. Population levels of A. flavus in soil
      samples ranged from zero to 1.2 * 10(3) CFU g(-1) of soil (based on culturable
      methods); however, the fungus was not detected with A. flavus-specific primers.
      The minimum threshold limit at which these aflatoxin-producing fungi could be
      detected from the total soil genomic DNA was determined through artificial
      inoculation of samples with 10-fold increases in concentrations. The results
      indicated that a minimum population density of 2.6 * 10(6) CFU g(-1) of soil is
      required for PCR detection in our conditions. These results are useful in further
      determining the relative population levels of these fungi in peanut soils with
      other soil fungi. This is a new approach to understanding soil fungal communities
      and how they might change over time and under different rotation systems.

PMID- 20822432
TI  - Assessment of the process of movement of Xylella fastidiosa within susceptible
      and resistant grape cultivars.
AB  - To better understand the processes contributing to symptoms and resistance to
      Pierce's disease of grape, we examined the movement and multiplication of a green
      fluorescent protein-marked strain of Xylella fastidiosa in the stems and petioles
      of Cabernet Sauvignon, Chenin Blanc, Roucaneuf, and Tampa grape cultivars that
      differ in their susceptibility to this disease. X. fastidiosa achieved much lower
      population sizes and colonized fewer xylem vessels in the stem of resistant
      cultivars compared with more susceptible cultivars. In contrast, X. fastidiosa
      achieved similarly high population sizes and colonized a similar proportion of
      the vessels in petioles of susceptible and resistant cultivars, suggesting that,
      compared with the stem, X. fastidiosa is relatively unrestricted in its movement
      and growth within the petiole. There was not a direct relationship between the
      population size of X. fastidiosa in the stem and the proportion of vessels
      colonized; a much higher population size of the pathogen was observed in
      susceptible cultivars than expected based on the proportion of vessels colonized.
      The high population sizes of X. fastidiosa in stems of susceptible genotypes were
      associated with both a high number of infected vessels and a much higher extent
      of colonization of those vessels that become infested than in more resistant
      cultivars. The formation of large cellular aggregates in vessels is not required
      for X. fastidiosa to move laterally in the stem to adjacent vessels because most
      vessels harbored only small assemblages, especially in resistant cultivars such
      as Roucaneuf, in which some intervessel movement was detected. Resistance to
      Pierce's disease is apparently not due to inhibitory compounds that circulate in
      the xylem because they might be expected to operate similarly in all tissues.

PMID- 20822433
TI  - A Bayesian approach to meta-analysis of plant pathology studies.
AB  - Bayesian statistical methods are used for meta-analysis in many disciplines,
      including medicine, molecular biology, and engineering, but have not yet been
      applied for quantitative synthesis of plant pathology studies. In this paper, we
      illustrate the key concepts of Bayesian statistics and outline the differences
      between Bayesian and classical (frequentist) methods in the way parameters
      describing population attributes are considered. We then describe a Bayesian
      approach to meta-analysis and present a plant pathological example based on
      studies evaluating the efficacy of plant protection products that induce systemic
      acquired resistance for the management of fire blight of apple. In a simple
      random-effects model assuming a normal distribution of effect sizes and no prior
      information (i.e., a noninformative prior), the results of the Bayesian meta
      analysis are similar to those obtained with classical methods. Implementing the
      same model with a Student's t distribution and a noninformative prior for the
      effect sizes, instead of a normal distribution, yields similar results for all
      but acibenzolar-S-methyl (Actigard) which was evaluated only in seven studies in
      this example. Whereas both the classical (P = 0.28) and the Bayesian analysis
      with a noninformative prior (95% credibility interval [CRI] for the log response
      ratio: -0.63 to 0.08) indicate a nonsignificant effect for Actigard, specifying a
      t distribution resulted in a significant, albeit variable, effect for this
      product (CRI: -0.73 to -0.10). These results confirm the sensitivity of the
      analytical outcome (i.e., the posterior distribution) to the choice of prior in
      Bayesian meta-analyses involving a limited number of studies. We review some
      pertinent literature on more advanced topics, including modeling of among-study
      heterogeneity, publication bias, analyses involving a limited number of studies,
      and methods for dealing with missing data, and show how these issues can be
      approached in a Bayesian framework. Bayesian meta-analysis can readily include
      information not easily incorporated in classical methods, and allow for a full
      evaluation of competing models. Given the power and flexibility of Bayesian
      methods, we expect them to become widely adopted for meta-analysis of plant
      pathology studies.

PMID- 20822434
TI  - Nivalenol-type populations of Fusarium graminearum and F. asiaticum are prevalent
      on wheat in southern Louisiana.
AB  - U.S. populations of the Fusarium graminearum clade cause head blight on wheat and
      barley and usually contaminate grain with the trichothecene mycotoxin
      deoxynivalenol (DON). Recently, however, individual nivalenol (NIV)-type isolates
      from the United States were described that belonged to either the newly described
      species F. gerlachii or the genetically distinct Gulf Coast population of F.
      graminearum sensu stricto (s.s.). Here, we describe the discovery of NIV-type F.
      graminearum s.s. populations that were found in high proportion (79%) among
      isolates from small-grain-growing regions of Louisiana. We genotyped 237 isolates
      from Louisiana with newly developed polymerase chain reaction (PCR) restriction
      fragment length polymorphism markers and multiplex PCR primers that distinguish
      among the three trichothecene types: the two DON types (15ADON and 3ADON) and
      NIV. These isolates were compared with 297 isolates from 11 other U.S. states,
      predominantly from the Midwest. Using Bayesian-model-based clustering, we
      discovered a southern Louisiana population of F. graminearum s.s. that was
      genetically distinct from the previously recognized pathogen population in the
      Midwest (MW15ADON population). Population membership was correlated with
      trichothecene type. Most isolates from the southern Louisiana population were of
      the NIV type, while the majority of the isolates from the Midwest were of the
      15ADON type. A smaller proportion of isolates from Louisiana belonged to the
      previously described Gulf Coast population that was mostly of the 3ADON type. The
      NIV type was also identified in collections from Arkansas (12%), North Carolina
      (40%), and Missouri (2%), with the collections from Arkansas and North Carolina
      being small and unrepresentative. F. asiaticum was detected from the two southern
      Louisiana parishes Acadia and Alexandria. All identified 41 F. asiaticum isolates
      were of the NIV type. Greenhouse tests indicated that U.S. NIV types accumulated
      four times less trichothecene toxin than DON types on inoculated wheat. This is
      the first report of NIV-type populations of F. graminearum s. s. and F. asiaticum
      in the United States.

PMID- 20822435
TI  - The development of problem solving in young children: a critical cognitive skill.
AB  - Problem solving is a signature attribute of adult humans, but we need to
      understand how this develops in children. Tool use is proposed as an ideal way to
      study problem solving in children less than 3 years of age because overt manual
      action can reveal how the child plans to achieve a goal. Motor errors are as
      informative as successful actions. Research is reviewed on intentional actions,
      beginning with block play and progressing to picking up a spoon in different
      orientations, and finally retrieving objects with rakes and from inside tubes.
      Behavioral and kinematic measures of motor action are combined to show different
      facets of skill acquisition and mastery. We need to design environments that
      encourage and enhance problem solving from a young age. One goal of this review
      is to excite interest and spur new research on the beginnings of problem solving
      and its elaboration during development.

PMID- 20822436
TI  - Early care, education, and child development.
AB  - Children growing up in the United States today typically spend a substantial
      portion of their early childhood years in early care and education (ECE)
      settings. These settings are thus an essential element of any effort to
      understand the ecology of early development. Research aimed at identifying the
      short- and long-term impacts of ECE experiences has a long history, the results
      of which now point to three key conclusions. (a) Although parents are the most
      important influence on children's development, ECE experiences have both short-
      and long-term impacts on a wide range of developmental outcomes that are best
      understood in interaction with family effects. (b) The quality of adult-child
      interactions in ECE settings is the most potent source of variation in child
      outcomes, although the amount of exposure to these settings also plays a role,
      perhaps especially with regard to social-emotional development. (c) Some
      children, notably those growing up in poverty, appear to be more vulnerable to
      variation in the quality of ECE settings than do other children. The frontiers of
      ECE research are addressing individual differences in children's responses to
      child care and approaching these settings both as sites for intervention research
      and as part of a wider web of important settings in young children's lives.

PMID- 20822437
TI  - The neuroscience of social decision-making.
AB  - Given that we live in highly complex social environments, many of our most
      important decisions are made in the context of social interactions. Simple but
      sophisticated tasks from a branch of experimental economics known as game theory
      have been used to study social decision-making in the laboratory setting, and a
      variety of neuroscience methods have been used to probe the underlying neural
      systems. This approach is informing our knowledge of the neural mechanisms that
      support decisions about trust, reciprocity, altruism, fairness, revenge, social
      punishment, social norm conformity, social learning, and competition. Neural
      systems involved in reward and reinforcement, pain and punishment, mentalizing,
      delaying gratification, and emotion regulation are commonly recruited for social
      decisions. This review also highlights the role of the prefrontal cortex in
      prudent social decision-making, at least when social environments are relatively
      stable. In addition, recent progress has been made in understanding the neural
      bases of individual variation in social decision-making.

PMID- 20822439
TI  - Psychological wisdom research: commonalities and differences in a growing field.
AB  - Wisdom represents a fruitful topic for psychological investigations for at least
      two reasons. First, the study of wisdom emphasizes the search for the continued
      optimization and the further cultural evolution of the human condition. Second,
      it exemplifies the collaboration of cognitive, emotional, and motivational
      processes. The growth and scope of psychological wisdom research over the past
      few decades demonstrate that it is possible to investigate this complex construct
      with empirical rigor. Since the 1970s, five main areas have been established: lay
      definitions of wisdom, conceptualizing and measuring wisdom, understanding the
      development of wisdom, investigating the plasticity of wisdom, and applying
      psychological knowledge about wisdom in life contexts.

PMID- 20822438
TI  - Long-term impact of prevention programs to promote effective parenting: lasting
      effects but uncertain processes.
AB  - This article reviews findings from 46 randomized experimental trials of
      preventive parenting interventions. The findings of these trials provide evidence
      of effects to prevent a wide range of problem outcomes and to promote
      competencies from one to 20 years later. However, there is a paucity of evidence
      concerning the processes that account for program effects. Three alternative
      pathways are proposed as a framework for future research on the long-term effects
      of preventive parenting programs: (a) through program effects on parenting
      skills, perceptions of parental efficacy, and reduction in barriers to effective
      parenting; (b) through program-induced reductions in short-term problems of youth
      that persist over time, improvements in youth adaptation to stress, and
      improvements in youth belief systems concerning the self and their relationships
      with others; and (c) through effects on contexts in which youth become involved
      and on youth-environment transactions.

PMID- 20822440
TI  - Genetic engineering of Escherichia coli for biofuel production.
AB  - In order to mitigate climate change without adversely affecting global energy
      supply, there is growing interest in the possibility of producing transportation
      fuels from renewable sources via microbial fermentation. Central to this
      challenge is the design of biocatalysts that can efficiently convert cheap
      lignocellulosic raw materials into liquid fuels. Owing to the wealth of genetic
      and metabolic knowledge associated with Escherichia coli, this bacterium is the
      most convenient starting point for engineering microbial catalysts for biofuel
      production. Here, we review the range of liquid fuels that can be produced in E.
      coli and discuss the underlying biochemistry that enables these metabolic
      products. The fundamental and technological challenges encountered in the
      development of efficient fermentation processes for biofuel production are
      highlighted. The example of biodiesel is a particularly illustrative case study
      and is therefore discussed in detail.

PMID- 20822441
TI  - Arbuscular mycorrhiza: the challenge to understand the genetics of the fungal
      partner.
AB  - Arbuscular mycorrhizal symbioses occur between fungi and the majority of plant
      species. They are important for plant nutrition, plant growth, protection from
      pathogens, plant diversity, nutrient cycling, and ecosystem processes. A key goal
      in research is to understand the molecular basis of the establishment,
      regulation, and functioning of the symbiosis. However, lack of knowledge on the
      genetics of the fungal side of this association has hindered progress. Here, we
      show how several key, recently discovered processes concerning the genetics of
      arbuscular mycorrhizal fungi could be essential for ultimately understanding the
      molecular genetics of this important symbiosis with plants.

PMID- 20822442
TI  - The genomic enzymology of antibiotic resistance.
AB  - The need for new antibiotic therapies is acute and growing in large part because
      of the emergence of drug-resistant pathogens. A vast number of resistance
      determinants are, however, found in nonpathogenic micro-organisms. The resistance
      totality in the global microbiota is the antibiotic resistome and includes not
      only established resistance genes but also genes that have the potential to
      evolve into resistance elements. We term these proto-resistance genes and
      hypothesize that they share common ancestry with other functional units known as
      housekeeping genes. Genomic enzymology is the study of protein structure-function
      in light of genetic context and evolution of protein superfamilies. This concept
      is highly applicable to study of antibiotic resistance evolution from proto
      resistance elements. In this review, we summarize some of the genomic enzymology
      evidence for resistance enzymes pointing to common ancestry with genes of other
      metabolic functions. Genomic enzymology plays a key role in understanding the
      origins of antibiotic resistance and aids in designing strategies for diagnosis
      and prevention thereof.

PMID- 20822443
TI  - Vision and visual navigation in nocturnal insects.
AB  - With their highly sensitive visual systems, nocturnal insects have evolved a
      remarkable capacity to discriminate colors, orient themselves using faint
      celestial cues, fly unimpeded through a complicated habitat, and navigate to and
      from a nest using learned visual landmarks. Even though the compound eyes of
      nocturnal insects are significantly more sensitive to light than those of their
      closely related diurnal relatives, their photoreceptors absorb photons at very
      low rates in dim light, even during demanding nocturnal visual tasks. To explain
      this apparent paradox, it is hypothesized that the necessary bridge between
      retinal signaling and visual behavior is a neural strategy of spatial and
      temporal summation at a higher level in the visual system. Exactly where in the
      visual system this summation takes place, and the nature of the neural circuitry
      that is involved, is currently unknown but provides a promising avenue for future
      research.

PMID- 20822444
TI  - The role of phytopathogenicity in bark beetle-fungus symbioses: a challenge to
      the classic paradigm.
AB  - The idea that phytopathogenic fungi associated with tree-killing bark beetles are
      critical for overwhelming tree defenses and incurring host tree mortality, herein
      called the classic paradigm (CP), has driven research on bark beetle-fungus
      symbiosis for decades. It has also strongly influenced our views of bark beetle
      ecology. We discuss fundamental flaws in the CP, including the lack of
      consistency of virulent fungal associates with tree-killing bark beetles, the
      lack of correspondence between fungal growth in the host tree and the development
      of symptoms associated with a successful attack, and the ubiquity of similar
      associations of fungi with bark beetles that do not kill trees. We suggest that,
      rather than playing a supporting role for the host beetle (tree killing),
      phytopathogenicity performs an important role for the fungi. In particular,
      phytopathogenicity may mediate competitive interactions among fungi and support
      survival and efficient resource capture in living, defensive trees.

PMID- 20822445
TI  - Robert F. Denno (1945-2008): insect ecologist extraordinaire.
AB  - Robert F. Denno was widely recognized as one of the leading insect ecologists in
      the world. He made major contributions to the study of plant-insect interactions,
      dispersal, interspecific competition, predator-prey interactions, and food web
      dynamics. He was especially well known for his detailed and comprehensive study
      of the arthropods that inhabit salt marshes. Denno promoted a research approach
      that included detailed knowledge of the natural history of the study system,
      meticulous experiments that often pushed logistical possibilities, and a focus on
      important ecological questions of the day. He was an enthusiastic collaborator
      and excellent mentor who invested incredible amounts of time and energy in the
      training and placement of graduate students and postdoctoral associates. As a
      result, Denno's legacy will continue to shape the field of insect ecology for
      generations to come.

PMID- 20822446
TI  - Arthropod-borne diseases associated with political and social disorder.
AB  - The living conditions and the crowded situations of the homeless, war refugees,
      or victims of a natural disaster provide ideal conditions for the spread of lice,
      fleas, ticks, flies and mites. The consequence of arthropod infestation in these
      situations is underestimated. Along with louse-borne infections such as typhus,
      trench fever, and relapsing fever, the relationship between Acinetobacter spp.
      infected lice and bacteremia in the homeless is not clear. Murine typhus,
      tungiasis, and myiasis are likely underestimated, and there has been a
      reemergence of bed bugs. Attempted eradication of the body louse, despite
      specific measures, has been disappointing, and infections with Bartonella
      quintana continue to be reported. The efficacy of ivermectin in eradicating the
      human body louse, although the effect is not sustained, might provide new
      therapeutic approaches. Arthropod-borne diseases continue to emerge within the
      deprived population. Public health programs should be engaged rapidly to control
      these pests and reduce the incidence of these transmissible diseases.

PMID- 20822447
TI  - The role of resources and risks in regulating wild bee populations.
AB  - Recent declines of bee species have led to great interest in preserving and
      promoting bee populations for agricultural and wild plant pollination. Many
      correlational studies have examined the indirect effects of factors such as
      landscape context and land management practices and found great variation in bee
      response. We focus here on the evidence for effects of direct factors (i.e., food
      resources, nesting resources, and incidental risks) regulating bee populations
      and then interpret varied responses to indirect factors through their species
      specific and habitat-specific effects on direct factors. We find strong evidence
      for food resource availability regulating bee populations, but little clear
      evidence that other direct factors are commonly limiting. We recommend
      manipulative experiments to illuminate the effects of these different factors. We
      contend that much of the variation in impact from indirect factors, such as
      grazing, can be explained by the relationships between indirect factors and
      floral resource availability based on environmental circumstances.

PMID- 20822448
TI  - Venom proteins from endoparasitoid wasps and their role in host-parasite
      interactions.
AB  - Endoparasitoids introduce a variety of factors into their host during oviposition
      to ensure successful parasitism. These include ovarian and venom fluids that may
      be accompanied by viruses and virus-like particles. An overwhelming number of
      venom components are enzymes with similarities to insect metabolic enzymes,
      suggesting their recruitment for expression in venom glands with modified
      functions. Other components include protease inhibitors, paralytic factors, and
      constituents that facilitate/enhance entry and expression of genes from symbiotic
      viruses or virus-like particles. In addition, the venom gland may itself support
      replication/production of some viruses or virus-like entities. Overlapping
      functions and structural similarities of some venom, ovarian, and virus-encoded
      proteins suggest coevolution of molecules recruited by endoparasitoids to
      maintain their fitness relative to their host.

PMID- 20822449
TI  - A roadmap for bridging basic and applied research in forensic entomology.
AB  - The National Research Council issued a report in 2009 that heavily criticized the
      forensic sciences. The report made several recommendations that if addressed
      would allow the forensic sciences to develop a stronger scientific foundation. We
      suggest a roadmap for decomposition ecology and forensic entomology hinging on a
      framework built on basic research concepts in ecology, evolution, and genetics.
      Unifying both basic and applied research fields under a common umbrella of
      terminology and structure would facilitate communication in the field and the
      production of scientific results. It would also help to identify novel research
      areas leading to a better understanding of principal underpinnings governing
      ecosystem structure, function, and evolution while increasing the accuracy of and
      ability to interpret entomological evidence collected from crime scenes. By
      following the proposed roadmap, a bridge can be built between basic and applied
      decomposition ecology research, culminating in science that could withstand the
      rigors of emerging legal and cultural expectations.

PMID- 20822450
TI  - Systematics and evolution of Heteroptera: 25 years of progress.
AB  - Heteroptera, or true bugs, are part of the most successful radiation of
      nonholometabolous insects. Twenty-five years after the first review on the
      influence of cladistics on systematic research in Heteroptera, we summarize
      progress, problems, and future directions in the field. The few hypotheses on
      infraordinal relationships conflict on crucial points. Understanding
      relationships within Gerromorpha, Nepomorpha, Leptopodomorpha, Cimicomorpha, and
      Pentatomomorpha is improving, but progress within Enicocephalomorpha and
      Dipsocoromorpha is lagging behind. Nonetheless, the classifications of several
      superfamily-level taxa within the Pentatomomorpha, such as Aradoidea, Coreoidea,
      and Pyrrhocoroidea, are still unaffected by cladistic studies. Progress in
      comparative morphology is slow and drastically impedes our understanding of the
      evolution of major clades. Molecular systematics has dramatically contributed to
      accelerating the generation and testing of hypotheses. Given the fascinating
      natural history of true bugs and their status as model organisms for evolutionary
      studies, integration of cladistic analyses in a broader biogeographic and
      evolutionary context deserves increased attention.

PMID- 20822451
TI  - Forest habitat conservation in Africa using commercially important insects.
AB  - African forests, which host some of the world's richest biodiversity, are rapidly
      diminishing. The loss of flora and fauna includes economically and socially
      important insects. Honey bees and silk moths, grouped under commercial insects,
      are the source for insect-based enterprises that provide income to forest-edge
      communities to manage the ecosystem. However, to date, research output does not
      adequately quantify the impact of such enterprises on buffering forest ecosystems
      and communities from climate change effects. Although diseases/pests of honey
      bees and silk moths in Africa have risen to epidemic levels, there is a dearth of
      practical research that can be utilized in developing effective control
      mechanisms that support the proliferation of these commercial insects as
      pollinators of agricultural and forest ecosystems. This review highlights the
      critical role of commercial insects within the environmental complexity of
      African forest ecosystems, in modern agroindustry, and with respect to its
      potential contribution to poverty alleviation and pollination services. It
      identifies significant research gaps that exist in understanding how insects can
      be utilized as ecosystem health indicators and nurtured as integral tools for
      important socioeconomic and industrial gains.

PMID- 20822452
TI  - Evolution of sexual dimorphism in the Lepidoptera.
AB  - Among the animals, the Lepidoptera (moths and butterflies) are second only to
      beetles in number of described species and are known for their striking intra-
      and interspecific diversity. Within species, sexual dimorphism is a source of
      variation in life history (e.g., sexual size dimorphism and protandry),
      morphology (e.g., wing shape and color pattern), and behavior (e.g., chemical and
      visual signaling). Sexual selection and mating systems have been considered the
      primary forces driving the evolution of sexual dimorphism in the Lepidoptera, and
      alternative hypotheses have been neglected. Here, we examine opportunities for
      sexual selection, natural selection, and the interplay between the two forces in
      the evolution of sexual differences in the moths and butterflies. Our primary
      goal is to identify mechanisms that either facilitate or constrain the evolution
      of sexual dimorphism, rather than to resolve any perceived controversy between
      hypotheses that may not be mutually exclusive.

PMID- 20822453
TI  - Evaluation of immunological cross-reactivity between clade A9 high-risk human
      papillomavirus types on the basis of E6-Specific CD4+ memory T cell responses.
AB  - CD4(+) T cell responses against the E6 oncoprotein of human papillomavirus (HPV)
      type 16 and 5 closely related members of clade A9 (HPV31, 33, 35, 52, and 58)
      were charted in peripheral blood mononuclear cell cultures from healthy subjects
      and patients who underwent HPV16 E6/E7-specific vaccination. Initial analyses
      with overlapping peptide arrays showed that approximately one-half of the
      responding subjects displayed reactivity against corresponding E6 peptides from
      >or=2 HPV types. This suggested immunological cross-reactivity and complicated
      retrospective evaluation of the infection history of the healthy subjects.
      Importantly, further dissection of the response by means of enriched and clonal T
      cell cultures (with protein antigen instead of peptides) revealed that CD4(+) T
      cells that are capable of efficiently reacting against E6 antigen from multiple
      HPV types are rare and only occur when epitope sequences are highly conserved.
      Our data indicate that natural and vaccine-induced HPV16 E6-specific CD4(+) T
      cell responses are unlikely to mediate efficient cross-protection against other
      clade A9 members.

PMID- 20822454
TI  - Influenza enhances susceptibility to natural acquisition of and disease due to
      Streptococcus pneumoniae in ferrets.
AB  - The role of respiratory viruses in the transmission of Streptococcus pneumoniae
      is poorly understood. Key questions, such as which serotypes are most fit for
      transmission and disease and whether influenza virus alters these parameters in a
      serotype-specific manner, have not been adequately studied. In a novel model of
      transmission in ferrets, we demonstrated that pneumococcal transmission and
      disease were enhanced if donors had previously been infected with influenza
      virus. Bacterial titers in nasal wash, the incidence of mucosal and invasive
      disease, and the percentage of contacts that were infected all increased. In
      contact ferrets, viral infection increased their susceptibility to S. pneumoniae
      acquisition both in terms of the percentage infected and the distance over which
      they could acquire infection. These influenza-mediated effects on colonization,
      transmission, and disease were dependent on the pneumococcal strain. Overall,
      these data argue that the relationship between respiratory viral infections,
      acquisition of pneumococci, and development of disease in humans needs further
      study to be better understood.

PMID- 20822456
TI  - Prenatal diagnosis of orofacial clefts: association with maternal satisfaction,
      team care, and treatment outcomes.
AB  - OBJECTIVE: Prenatal diagnosis of an orofacial cleft is thought to allow mothers
      greater opportunity to become prepared for the special needs of an infant with a
      cleft and plan for the care of their child. Using a population-based sample, we
      determined which children were more likely to be diagnosed prenatally, and
      whether early diagnosis was associated with maternal satisfaction and treatment
      outcomes. DESIGN: Interviews were completed with 235 (49% of eligible) mothers of
      children ages 2 to 7 with orofacial clefts initially enrolled in the National
      Birth Defects Prevention Study from the Arkansas, Iowa, and New York sites.
      Maternal satisfaction with information, support, and treatment outcomes was
      compared between women who received a prenatal diagnosis and those who did not.
      RESULTS: Of 235 infants with clefts, 46 (19.6%) were identified prenatally. One
      third of mothers were somewhat or not satisfied with information provided by
      medical staff. Satisfaction did not vary by timing of the diagnosis. Infants
      diagnosed prenatally were no more likely to have received care provided by a
      recognized multidisciplinary cleft team (76%) than were infants diagnosed at
      birth (78%). Speech problems and facial appearance as rated by the mother did not
      vary by timing of the diagnosis. CONCLUSIONS: Timing of the cleft diagnosis did
      not alter maternal satisfaction with information, whether care was provided by a
      designated cleft team, or maternal perception of facial appearance or speech.
      Further research should determine whether prenatal diagnoses alter maternal
      anxiety or influence postnatal morbidity.

PMID- 20822459
TI  - Infectious diseases in the nursing home setting: challenges and opportunities for
      clinical investigation.
AB  - The global population is aging. With the high prevalence of dementia and
      functional decline in older Americans, many aging adults with disabilities reside
      in nursing homes in their final stage of life. Immunosenescence, multiple
      comorbid diseases, and grouped quarter living all coalesce in nursing home
      residents to increase the risk for infectious disease. The unique issues involved
      with diagnosis, prognosis, and management of infectious diseases in nursing home
      residents make research based in the nursing home setting both necessary and
      exciting for the physician investigator. This review discusses the opportunities
      and challenges involved with research of the evolving public health problem of
      infections among nursing home residents.

PMID- 20822460
TI  - Near infrared light reduces oxidative stress and preserves function in CNS tissue
      vulnerable to secondary degeneration following partial transection of the optic
      nerve.
AB  - Traumatic injury to the central nervous system (CNS) is accompanied by the
      spreading damage of secondary degeneration, resulting in further loss of neurons
      and function. Partial transection of the optic nerve (ON) has been used as a
      model of secondary degeneration, in which axons of retinal ganglion cells in the
      ventral ON are spared from initial dorsal injury, but are vulnerable to secondary
      degeneration. We have recently demonstrated that early after partial ON injury,
      oxidative stress spreads through the ventral ON vulnerable to secondary
      degeneration via astrocytes, and persists in the nerve in aggregates of cellular
      debris. In this study, we show that diffuse transcranial irradiation of the
      injury site with far red to near infrared (NIR) light (WARP 10 LED array, center
      wavelength 670 nm, irradiance 252 W/m(-2), 30 min exposure), as opposed to
      perception of light at this wavelength, reduced oxidative stress in areas of the
      ON vulnerable to secondary degeneration following partial injury. The WARP 10 NIR
      light treatment also prevented increases in NG-2-immunopositive oligodendrocyte
      precursor cells (OPCs) that occurred in ventral ON as a result of partial ON
      transection. Importantly, normal visual function was restored by NIR light
      treatment with the WARP 10 LED array, as assessed using optokinetic nystagmus and
      the Y-maze pattern discrimination task. To our knowledge, this is the first
      demonstration that 670-nm NIR light can reduce oxidative stress and improve
      function in the CNS following traumatic injury in vivo.

PMID- 20822461
TI  - Early and sustained increase in the expression of hippocampal IGF-1, but not EPO,
      in a developmental rodent model of traumatic brain injury.
AB  - Pediatric traumatic brain injury (pTBI) is the leading cause of traumatic death
      and disability in children in the United States. Impaired learning and memory in
      these young survivors imposes a heavy toll on society. In adult TBI (aTBI)
      models, cognitive outcome improved after administration of erythropoietin (EPO)
      or insulin-like growth factor-1 (IGF-1). Little is known about the production of
      these agents in the hippocampus, a brain region critical for learning and memory,
      after pTBI. Our objective was to describe hippocampal expression of EPO and IGF
      1, together with their receptors (EPOR and IGF-1R, respectively), over time after
      pTBI in 17-day-old rats. We used the controlled cortical impact (CCI) model and
      measured hippocampal mRNA levels of EPO, IGF-1, EPOR, IGF-1R, and markers of
      caspase-dependent apoptosis (bcl2, bax, and p53) at post-injury days (PID) 1, 2,
      3, 7, and 14. CCI rats performed poorly on Morris water maze testing of spatial
      working memory, a hippocampally-based cognitive function. Apoptotic markers were
      present early and persisted for the duration of the study. EPO in our pTBI model
      increased much later (PID7) than in aTBI models (12 h), while EPOR and IGF-1
      increased at PID1 and PID2, respectively, similar to data from aTBI models. Our
      data indicate that EPO expression showed a delayed upregulation post-pTBI, while
      EPOR increased early. We speculate that administration of EPO in the first 1-2
      days after pTBI would increase hippocampal neuronal survival and function.

PMID- 20822462
TI  - Diffusion tensor imaging and fiber tractography of patients with cervical spinal
      cord injury.
AB  - To verify the usefulness of diffusion tensor imaging (DTI) and fiber tractography
      (FT) compared with routine magnetic resonance imaging (MRI) in patients with
      cervical spinal cord injury, and to clarify the relationship between motor and
      sensory impairments and DTI and FT parameters, we performed routine MRI and DTI
      on 10 patients with chronic cervical spinal cord injury and on 10 controls.
      Quantitative parameters of DTI, such as fractional anisotropy (FA) and apparent
      diffusion coefficient (ADC), were calculated for each cervical cord level. FT
      parameters of imaginary crossing fiber numbers were also determined at the C3
      level, from C3-C6, and from C3-C7, as well as each connection rate. All patients'
      clinical motor and sensory functions were examined using the International
      Standards for the Neurological Classification of Spinal Cord Injury (ISCSCI). FA
      values in the controls and patients were 0.76 +/- 0.08 (mean +/- standard
      deviation) and 0.58 +/- 0.11, respectively, and ADC values in the controls and
      patients were 1.29 +/- 0.75 * 10(-3) mm(2)/sec and 1.26 +/- 0.66 * 10(-3)
      mm(2)/sec, respectively. In patients with cervical cord injury, abnormal cervical
      levels detected on routine MRI were not correlated with clinical findings and DTI
      parameters, but FA of DTI was correlated with motor function, as were imaginary
      crossing fiber numbers and connection rates of FT. Quantitative DTI and FT
      analyses were useful in the evaluation of patients with cervical spinal cord
      injury. The injured cervical spinal cord can be evaluated in more detail and more
      precisely using DTI and FT, for which findings are correlated with clinical
      findings such as neurological impairments.

PMID- 20822463
TI  - Sympathetic vasoconstriction is potentiated in arteries caudal but not rostral to
      a spinal cord transection in rats.
AB  - Sympathetic nerve-mediated contractions of mesenteric and tail arteries
      controlled by preganglionic neurones decentralized by a spinal cord injury (SCI)
      are potentiated, and likely contribute to autonomic dysreflexia. However,
      reactivity to the alpha(1)-adrenoceptor agonist phenylephrine has been reported
      to be enhanced in vascular beds controlled by preganglionic neurones lying both
      rostral and caudal to an SCI in vivo. Here responses of isometrically-mounted
      median and saphenous arteries isolated from rats 2 and 8 weeks after transection
      of the T4 spinal cord have been compared with those from sham-operated rats.
      After SCI, contractions of median arteries to perivascular nerve stimulation, to
      alpha-adrenoceptor agonists (phenylephrine and clonidine), to the P2X
      purinoceptor agonist alpha,beta-methylene ATP, and to 60 mM K(+) were unchanged.
      Blockade of nerve-evoked contractions by alpha-adrenoceptor antagonists (prazosin
      and idazoxan) was not affected by SCI in either the median or saphenous arteries.
      In contrast, at 2 and 8 weeks after SCI, nerve-evoked contractions of saphenous
      arteries were potentiated. Saphenous arteries were less sensitive to
      phenylephrine 8 weeks after SCI, and their contractions to 60 mM K(+) were
      reduced. However, the sensitivity of saphenous arteries to clonidine was
      unchanged by SCI. Eight weeks after SCI, the reactivity of saphenous arteries to
      alpha,beta-methylene ATP was unchanged, but the P2-antagonist suramin produced
      more blockade of nerve-evoked contractions. These findings demonstrate that
      neurovascular transmission is enhanced in arteries located caudal, but not
      rostral, to a spinal transection. In the saphenous artery, the most likely
      explanation seems to be an increase in neurotransmitter release, as may occur in
      other inactive sympathetic pathways caudal to the lesion.

PMID- 20822464
TI  - Repetitive intrathecal catheter delivery of bone marrow mesenchymal stromal cells
      improves functional recovery in a rat model of contusive spinal cord injury.
AB  - Transplantation of bone marrow mesenchymal stromal cells (MSCs) has been shown to
      improve the functional recovery in various models of spinal cord injury (SCI).
      However, the issues of the optimal dose, timing, and route of MSC application are
      crucial factors in achieving beneficial therapeutic outcomes. The objective of
      this study was to standardize the intrathecal (IT) catheter delivery of rat MSCs
      after SCI in adult rats. MSCs labeled with PKH-67 were administered by IT
      delivery to rats at 3 or 7 days after SCI as one of the following treatment
      regimens: (1) a single injection (5*10(5) MSCs/rat), or (2) as three daily
      injections (5*10(5) MSCs/rat/d for a total of 1.5*10(6) MSCs/rat over 3 days,
      injected on days 3, 4, and 5, or days 7, 8, and 9 following SCI. The animals were
      behaviorally tested for 4 weeks using the Basso, Beattie, and Bresnahan (BBB)
      locomotor rating scale, and histologically assessed for MSC survival,
      distribution, and engraftment properties after 28 days. Rats treated with a
      single injection of MSCs at 3 or 7 days post-injury showed a modest, non
      significant improvement in function and low survival of grafted MSCs, which were
      found attached to the pia mater or accumulated around the anterior spinal artery.
      In contrast, rats treated with three daily injections of MSCs at days 7, 8, and
      9, but not on days 3, 4, and 5, showed significantly higher motor function
      recovery (BBB score 16.8+/-1.7) at 14-28 days post-injury. Transplanted PKH-67
      MSCs were able to migrate and incorporate into the central lesion. However, only
      a limited number of surviving MSCs, ranging from 24,128+/-1170 to 116,258+/-8568
      cells per graft, were observed within the damaged white matter. These results
      suggest that repetitive IT transplantation, which imposes a minimal burden on the
      animals, may improve behavioral function when the dose, timing, and targeted IT
      delivery of MSCs towards the lesion cavity are optimized.

PMID- 20822465
TI  - The effect of spontaneous alterations in brain temperature on outcome: a
      prospective observational cohort study in patients with severe traumatic brain
      injury.
AB  - There are few prospective studies reporting the effect of spontaneous temperature
      changes on outcome after severe traumatic brain injury (TBI). Where studies have
      been conducted, results are based on systemic rather than brain temperature per
      se. However, body temperature is not a reliable surrogate for brain temperature.
      Consequently, the effect of brain temperature changes on outcome in the acute
      phase after TBI is not clear. Continuous intraparenchymal brain temperature was
      measured in consecutive admissions of severe TBI patients during the course of
      the first 5 days of admission to the intensive care unit (ICU). Patients received
      minimal temperature altering therapy during their ICU stay. Logistic regression
      was used to explore the relationship between the initial, the 24-h mean, and the
      48-h mean brain temperature with outcome for mortality at 30 days and outcome at
      3 months. Multifactorial analysis was performed to account for potential
      confounders. At the 24-h time point, brain temperature within the range of 36.5
      degrees C to 38 degrees C was associated with a lower probability of death (10
      20%). Brain temperature outside of this range was associated with a higher
      probability of death and poor 3-month neurological outcome. After adjusting for
      other predictors of outcome, low brain temperature was independently associated
      with a worse outcome. Lower brain temperatures (below 37 degrees C) are
      independently associated with a higher mortality rate after severe TBI. The
      results suggest that, contrary to current opinion, temperatures within the normal
      to moderate fever range during the acute post-TBI period do not impose an
      additional risk for a poor outcome after severe TBI.

PMID- 20822466
TI  - Post-traumatic hypoxia exacerbates brain tissue damage: analysis of axonal injury
      and glial responses.
AB  - Traumatic brain injury (TBI) resulting in poor neurological outcome is
      predominantly associated with diffuse brain damage and secondary hypoxic insults.
      Post-traumatic hypoxia is known to exacerbate primary brain injury; however, the
      underlying pathological mechanisms require further elucidation. Using a rat model
      of diffuse traumatic axonal injury (TAI) followed by a post-traumatic hypoxic
      insult, we characterized axonal pathology, macrophage/microglia accumulation, and
      astrocyte responses over 14 days. Rats underwent TAI alone, TAI followed by 30
      min of hypoxia (TAI + Hx), hypoxia alone, or sham-operation (n = 6/group).
      Systemic hypoxia was induced by ventilating rats with 12% oxygen in nitrogen,
      resulting in a ~ 50% reduction in arterial blood oxygen saturation. Brains were
      assessed for axonal damage, macrophage/microglia accumulation, and astrocyte
      activation at 1, 7, and 14 days post-treatment. Immunohistochemistry with axonal
      damage markers (beta-amyloid precursor protein [beta-APP] and neurofilament)
      showed strong positive staining in TAI + Hx rats, which was most prominent in the
      corpus callosum (retraction bulbs 69.8 +/- 18.67; swollen axons 14.2 +/- 5.25),
      and brainstem (retraction bulbs 294 +/- 118.3; swollen axons 50.3 +/- 20.45) at 1
      day post-injury. Extensive microglia/macrophage accumulation detected with the
      CD68 antibody was maximal at 14 days post-injury in the corpus callosum
      (macrophages 157.5 +/- 55.48; microglia 72.71 +/- 20.75), and coincided with
      regions of axonal damage. Astrocytosis assessed with glial fibrillary acidic
      protein (GFAP) antibody was also abundant in the corpus callosum and maximal at
      14 days, with a trend toward an increase in TAI + Hx animals (18.99 +/- 2.45
      versus 13.56 +/- 0.81; p = 0.0617). This study demonstrates for the first time
      that a hypoxic insult following TAI perpetuates axonal pathology and cellular
      inflammation, which may account for the poor neurological outcomes seen in TBI
      patients who experience post-traumatic hypoxia.

PMID- 20822468
TI  - Atraumatic removal of an asymptomatic migrated dental implant into the maxillary
      sinus: a case report.

PMID- 20822469
TI  - Surgical relocation of a malpositioned, unserviceable implant protruding into the
      maxillary sinus cavity. A clinical report.
AB  - Malpositioned implants always result in significant mechanical and aesthetic
      restorative challenges. This case report describes the correction of position of
      an unserviceable osseointegrated implant also protruding into the maxillary sinus
      cavity. This surgical technique facilitated the relocation of an implant-bony
      segment into a more favorable aesthetic and biomechanical position in a single
      stage surgery.

PMID- 20822470
TI  - Jaw bite force measurement device.
AB  - We describe a cost-effective device that uses an off-the-shelf force transducer
      to measure patient bite force as a diagnostic aid in determining dental implant
      size, number of implants, and prosthetic design for restoring partial edentulism.
      The main advantages of the device are its accuracy, simplicity, modularity, ease
      of manufacturing, and low cost.

PMID- 20822471
TI  - Genetics of early onset cognitive impairment.
AB  - Intellectual disability (ID) is the leading socio-economic problem of health
      care, but compared to autism and schizophrenia, it has received very little
      public attention. Important risk factors for ID are malnutrition, cultural
      deprivation, poor health care, and parental consanguinity. In the Western world,
      fetal alcohol exposure is the most common preventable cause. Most severe forms of
      ID have genetic causes. Cytogenetically detectable and submicroscopic chromosomal
      rearrangements account for approximately 25% of all cases. X-linked gene defects
      are responsible in 10-12% of males with ID; to date, 91 of these defects have
      been identified. In contrast, autosomal gene defects have been largely
      disregarded, but due to coordinated efforts and the advent of next-generation DNA
      sequencing, this is about to change. As shown for Fra(X) syndrome, this renewed
      focus on autosomal gene defects will pave the way for molecular diagnosis and
      prevention, shed more light on the pathogenesis of ID, and reveal new
      opportunities for therapy.

PMID- 20822472
TI  - Peripartum serum leptin and soluble leptin receptor levels in women with
      gestational diabetes.
AB  - The purpose of the study was to clarify the alterations in serum leptin and
      soluble leptin receptor levels at term and early postpartum in gestational
      diabetes mellitus (GDM). Twenty women with normal pregnancy and 20 with GDM were
      recruited and blood samples were taken on the day of delivery and Days 1, 3 and 5
      after delivery. Serum leptin levels were significantly higher in women with GDM
      than in the controls before delivery and decreased significantly after delivery
      (p < 0.001). After delivery there were no significant differences in serum leptin
      concentrations between women with GDM and the controls. Serum soluble leptin
      receptor concentrations did not differ neither between the two groups, nor before
      or after delivery. Leptin may play a role in GDM through a positive correlation
      with insulin resistance.

PMID- 20822473
TI  - Partners towards autonomy: risky choices and relational autonomy in
      rehabilitation care.
AB  - PURPOSE: A common source of ethical challenge for health care professionals
      (HCPs) in rehabilitation is situations when patients wish to make risky choices
      not related or contrary to rehabilitation goals. We explore the potential
      contribution of a relational understanding of autonomy for orienting clinical
      practice when patients wish to enact choices with associated risks for the
      patient or others. METHOD: We provide a theoretical analysis that is oriented by
      an examination of risk and a relational conception of autonomy, as relevant to
      rehabilitation care. We illustrate our analysis through the examination of a
      clinical case. RESULTS: Relational autonomy assumes that the patient, and the
      patient's decisional autonomy, is situated and shaped by relationships. From this
      perspective, HCPs can engage in a process of communication and deliberation with
      the patient about the risky choices at issue, leading towards improved patient
      autonomy. CONCLUSIONS: Relational autonomy can contribute to understanding
      patients' risky choices and guiding HCPs as they partner with patients towards
      autonomy. Such an approach supports patient-centred rehabilitation care.
      Ultimately, as clinicians respond to a patient who wishes to enact a risky
      choice, they should aim for a partnership towards autonomy with the patient and
      family.

PMID- 20822474
TI  - Acupressure to reduce labor pain: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effect of acupressure administered during the active
      phase of labor on nulliparous women's ratings of labor pain. DESIGN: Randomized
      controlled trial. SETTING: Public hospital in India. SAMPLE: Seventy-one women
      randomized to receive acupressure at acupuncture point spleen 6 (SP6) on both
      legs during contractions over a 30-minute period (acupressure group), 71 women to
      receive light touch at SP6 on both legs during the same period of time (touch
      group) and 70 women to receive standard care (standard care group). METHODS:
      Experience of in-labor pain was assessed by visual analog scale at baseline
      before treatment, immediately after treatment, and at 30, 60 and 120 minutes
      after treatment. MAIN OUTCOME MEASURE: Labor pain intensity at different time
      intervals after treatment compared with before treatment. RESULTS: A reduction of
      in-labor pain was found in the acupressure group and was most noticeable
      immediately after treatment (acupressure group vs. standard care group p < 0.001;
      acupressure group vs. touch group p < 0.001). CONCLUSION: Acupressure seems to
      reduce pain during the active phase of labor in nulliparous women giving birth in
      a context in which social support and epidural analgesia are not available.
      However, the treatment effect is small which suggests that acupressure may be
      most effective during the initial phase of labor.

PMID- 20822475
TI  - Application of ICF in clinical settings across Europe.

PMID- 20822476
TI  - The role of ERK1/2 in 15-HETE-inhibited apoptosis in pulmonary arterial smooth
      muscle cells.
AB  - 15-Hydroxyeicosatetrenoic acid (15-HETE) is an important product of arachidonic
      acid catalyzed by 15-lipoxygenase (15-LO) in the wall of pulmonary vessels, which
      plays a key role in pulmonary arterial hypertension. The previous studies showed
      that 15-HETE inhibits apoptosis. It is still unknown, however, whether 15-HETE
      acts on the apoptotic responses through the extracellular signal-regulated kinase
      1/2 (ERK1/2) pathway. The aim of the study is to test the hypothesis that ERK1/2
      pathway participates in the protective effects of 15-HETE on the cell survival.
      This hypothesis was validated by cell viability measurement, nuclear morphology
      determination, terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling (TUNEL) assay, mitochondrial potentials assay and Western blot. We found
      that 15-HETE enhanced cell survival, suppressed the expression of phosphatase and
      tensin homologue deleted on chromosome ten, upregulated X-linked inhibitor of
      apoptosis protein and Bcl-2 and attenuated mitochondrial depolarization in
      pulmonary artery muscle smooth cells (PASMCs) under serum-deprived conditions.
      These effects were reversed by ERK1/2 inhibitor PD98059. Taken together, our data
      indicated that the ERK1/2 kinase is a regulator of PASMC apoptosis, and potential
      therapeutical strategy for pulmonary hypertension may be developed by targeting
      at intracellular signaling systems centered by the kinase.

PMID- 20822478
TI  - In-silico characterization of the effects of phosphorylated tyrosines 86 and 106
      on structure and binding of MAL: insight into hyperinflammatory response to
      infection by the human malaria parasites.
AB  - The innate immune system uses inflammation to respond to infection of humans by
      various parasitic organisms and in some individuals can produce a
      hyperinflammatory response to infection by the human malaria parasites Plasmodium
      falciparum and vivax, leading to a more severe form of the disease-cerebral
      malaria (CM). Toll-like receptors (TLRs) 2 and 4 and members of its signaling
      pathway, including myeloid differentiation primary response protein (MyD88),
      MyD88 adapter-like protein (MAL) and suppressor of cytokine signaling 1 (SOCS1),
      are involved in this inflammatory response. A number of studies have suggested a
      possible role for MAL in developing CM and that modulating the behavior of MAL
      may prevent such complications. Mutagenesis studies have suggested that MAL
      becomes active after phosphorylation of tyrosines and the computational studies
      presented here characterize the possible roles of two tyrosines-Tyr86 and Tyr106
      in MAL activity. The effects of phosphorylation on the structure of MAL and on
      its binding with two binding partners MyD88 and SOCS1 are studied here. The
      results suggest that phosphorylation of Tyr86 leads to conformational changes in
      the BB loop of MAL, and this conformational switch forms the interface for
      binding with MyD88. Similarly, our results suggest that phosphorylation of Tyr106
      contributes to the stability of MAL-MyD88 dimer formation, and may form a
      possible binding site for SOCS1. Thus, our study supports roles for tyrosines 86
      and 106 in signaling pathways involving MAL, and hence as potential drug targets
      against hyperinflammatory response to infection by Plasmodium falciparum and
      vivax.

PMID- 20822479
TI  - Pharmacokinetics, antifungal activity and clinical efficacy of anidulafungin in
      the treatment of fungal infections.
AB  - IMPORTANCE OF THE FIELD: Anidulafungin is one of three available intravenous
      echinocandins that plays an important role in the treatment of serious fungal
      infections. Currently, anidulafungin is approved for the treatment of esophageal
      candidiasis, candidemia and other invasive Candida infections including intra
      abdominal abscesses and peritonitis. AREAS COVERED IN THIS REVIEW: This paper
      covers a comprehensive review of anidulafungin. WHAT THE READER WILL GAIN: The
      reader will be provided the most recent data available regarding the
      pharmacology, pharmacokinetics, in vitro activity and clinical utility of
      anidulafungin for the treatment of serious fungal infections. TAKE HOME MESSAGE:
      Echinocandin antifungals, such as anidulafungin, are now considered first line
      for the treatment of candidemia and invasive candidiasis, particularly in
      critically ill patients or those who have previously received azole therapy.
      Anidulafungin has potent in vitro activity against Candida and Aspergillus
      species, predictable pharmacokinetics that does not require dosage adjustment,
      few drug interactions and is well tolerated. Because of these favorable
      characteristics, anidulafungin is an important addition to our antifungal
      armamentarium.

PMID- 20822480
TI  - Increased mixing improves hydrogel homogeneity and quality of three-dimensional
      printed constructs.
AB  - As the tissue engineering and drug delivery communities place greater emphasis on
      producing constructs of prescribed geometry and organization, three-dimensional
      printing is becoming as an increasingly important technique. While numerous
      tissue printing techniques have emerged, little has been done to characterize the
      properties of printing inks and the resultant effects on geometric fidelity, cell
      viability, and mechanical integrity. These questions have been neglected largely
      because of the lack of methods to characterize the real-time properties of
      printing inks. We present a novel technique for characterizing the homogeneity of
      hydrogel tissue printing inks that measures loads during ink deposition and its
      temporal variation, called, mechanical noise. We then used this technique to
      determine the effects of increased mixing on the homogeneity of alginate
      hydrogels and determined whether this results in improved geometric fidelity of
      printed constructs. We also studied potential adverse effects on cell viability
      and mechanical integrity of printed parts. Increased mixing between alginate and
      crosslinker to 128 cycles yielded an 82% reduction in mechanical noise. Geometric
      fidelity also improved with this increased mixing, in terms of a smoother surface
      texture, better matching of the target geometry, and fewer point defects.
      Viability was not adversely affected by increased mixing, and it actually
      improved by 34% with a 45 min curing time. As mixing before printing was
      increased from 8 to 200 cycles, the modulus also increased by 110% from 4.0  +/- 
      0.1 to 8.4  +/-  1.0 kPa. The results presented herein motivate a radical shift
      in alginate printing protocol, and also propose a useful methodology for
      characterizing three-dimensional printing materials.

PMID- 20822477
TI  - Production of adenovirus vectors and their use as a delivery system for influenza
      vaccines.
AB  - IMPORTANCE OF THE FIELD: With the emergence of highly pathogenic avian influenza
      H5N1 viruses that have crossed species barriers and are responsible for lethal
      infections in humans in many countries, there is an urgent need for the
      development of effective vaccines which can be produced in large quantities at a
      short notice and confer broad protection against these H5N1 variants. In order to
      meet the potential global vaccine demand in a pandemic scenario, new vaccine
      production strategies must be explored in addition to the currently used egg
      based technology for seasonal influenza. AREAS COVERED IN THIS REVIEW: Adenovirus
      (Ad) based influenza vaccines represent an attractive alternative/supplement to
      the currently licensed egg-based influenza vaccines. Ad-based vaccines are
      relatively inexpensive to manufacture, and their production process does not
      require either chicken eggs or labor-intensive and time-consuming processes
      necessitating enhanced biosafety facilities. Most importantly, in a pandemic
      situation, this vaccine strategy could offer a stockpiling option to reduce the
      response time before a strain-matched vaccine could be developed. WHAT THE READER
      WILL GAIN: This review discusses Ad-vector technology and the current progress in
      the development of Ad-based influenza vaccines. TAKE HOME MESSAGE: Ad vector
      based influenza vaccines for pandemic preparedness are under development to meet
      global vaccine demand.

PMID- 20822481
TI  - Consistent osteoblastic differentiation of human mesenchymal stem cells with bone
      morphogenetic protein 4 and low serum.
AB  - Providing fully mature and functional osteoblasts is challenging for bone tissue
      engineering and regenerative medicine. Such cells could be obtained from
      multipotent bone marrow mesenchymal stem cells (MSCs) after induction by
      different osteogenic factors. However, there are some discrepancies in results,
      notably due to the use of sera and to the type of osteogenic factor. In this
      study, we compared the osteogenic differentiation of bone marrow MSCs induced by
      dexamethasone (Dex) or bone morphogenetic proteins (BMPs) by assessing phenotypes
      in vitro and functional osteoblasts in vivo. Reducing the content of fetal calf
      serum from 10% to 2% significantly increased the mineral deposition and
      expression of osteoblastic markers during osteogenesis. In comparison to Dex
      condition, the addition of BMP4 greatly improved the differentiation of MSCs into
      fully mature osteoblasts as seen by high expression of Osterix. These results
      were confirmed in different supportive matrixes, plastic flasks, or biphasic
      calcium phosphate biomaterials. In contrast to Dex-derived osteoblasts, BMP4
      derived osteoblasts from MSCs were significantly able to produce new bone in
      subcutis of nude mice in accordance with in vitro results. In conclusion, we
      describe a convenient ex vivo method to produce consistently mature functional
      osteoblasts from human MSCs with use of BMP4 and low serum.

PMID- 20822482
TI  - The importance of raising the profile of alcohol hangover research.

PMID- 20822483
TI  - Evolutionary origin of the cell nucleus and its functional architecture.
AB  - Understanding the evolutionary origin of the nucleus and its compartmentalized
      architecture provides a huge but, as expected, greatly rewarding challenge in the
      post-genomic era. We start this chapter with a survey of current hypotheses on
      the evolutionary origin of the cell nucleus. Thereafter, we provide an overview
      of evolutionarily conserved features of chromatin organization and arrangements,
      as well as topographical aspects of DNA replication and transcription, followed
      by a brief introduction of current models of nuclear architecture. In addition to
      features which may possibly apply to all eukaryotes, the evolutionary plasticity
      of higher-order nuclear organization is reflected by cell-type- and species
      specific features, by the ability of nuclear architecture to adapt to specific
      environmental demands, as well as by the impact of aberrant nuclear organization
      on senescence and human disease. We conclude this chapter with a reflection on
      the necessity of interdisciplinary research strategies to map epigenomes in space
      and time.

PMID- 20822484
TI  - Spatial epigenetics: linking nuclear structure and function in higher eukaryotes.
AB  - Eukaryotic cells are defined by the genetic information that is stored in their
      DNA. To function, this genetic information must be decoded. In doing this, the
      information encoded in DNA is copied first into RNA, during RNA transcription.
      Primary RNA transcripts are generated within transcription factories, where they
      are also processed into mature mRNAs, which then pass to the cytoplasm. In the
      cytoplasm these mRNAs can finally be translated into protein in order to express
      the genetic information as a functional product. With only rare exceptions, the
      cells of an individual multicellular eukaryote contain identical genetic
      information. However, as different genes must be expressed in different cell
      types to define the structure and function of individual tissues, it is clear
      that mechanisms must have evolved to regulate gene expression. In higher
      eukaryotes, mechanisms that regulate the interaction of DNA with the sites where
      nuclear functions are performed provide one such layer of regulation. In this
      chapter, I evaluate how a detailed understanding of nuclear structure and
      chromatin dynamics are beginning to reveal how spatial mechanisms link chromatin
      structure and function. As these mechanisms operate to modulate the genetic
      information in DNA, the regulation of chromatin function by nuclear architecture
      defines the concept of 'spatial epigenetics'.

PMID- 20822485
TI  - Epigenetic markers and their cross-talk.
AB  - Post-translational modifications of histone proteins in conjunction with DNA
      methylation represent important events in the regulation of local and global
      genome functions. Advances in the study of these chromatin modifications
      established temporal and spatial co-localization of several distinct 'marks' on
      the same histone and/or the same nucleosome. Such complex modification patterns
      suggest the possibility of combinatorial effects. This idea was originally
      proposed to establish a code of histone modifications that regulates the
      interpretation of the genetic code of DNA. Indeed, interdependency of different
      modifications is now well documented in the literature. Our current understanding
      is that the function of a given histone modification is influenced by
      neighbouring or additional modifications. Such context sensitivity of the readout
      of a modification provides more flexible translation than would be possible if
      distinct modifications function as isolated units. The mechanistic principles for
      modification cross-talk can originate in the modulation of the activity of
      histone-modifying enzymes or may be due to selective recognition of these marks
      via modification of specific binding proteins. In the present chapter, we discuss
      fundamental biochemical principles of modification cross-talk and reflect on the
      interplay of chromatin marks in cellular signalling, cell-cycle progression and
      cell-fate determination.

PMID- 20822486
TI  - Nucleosome dynamics and epigenetic stability.
AB  - Nucleosome remodelling is an essential principle to assure that the packaging of
      eukaryotic genomes in chromatin remains flexible and adaptable to regulatory
      needs. Nucleosome remodelling enzymes spend the energy of ATP to alter histone
      DNA interactions, to catalyse nucleosome displacement and reassembly, on histone
      exchange and on the relocation of histone octamers on DNA. Despite these
      dynamics, chromatin structures encode 'epigenetic' information that governs the
      expression of the underlying genes. These information-bearing structures must be
      maintained over extended periods of time in resting cells and may be sufficiently
      stable to resist the turmoil of the cell cycle to be passed on to the next cell
      generation. Intuitively, nucleosome remodelling should antagonize the maintenance
      of stable structures. However, upon closer inspection it becomes evident that
      nucleosome remodelling is intimately involved in the assembly of stable chromatin
      structures that correspond to functional states. Remodellers may even contribute
      structural information themselves. Their involvement can be seen at several
      structural levels: at the levels of positioning individual nucleosomes,
      homoeostasis of linker histones, histone variants and non-histone proteins, as
      well as the differential folding of the nucleosome fibre. All of them may
      contribute to the assembly of heritable epigenetic structures.

PMID- 20822487
TI  - Nucleosome dynamics and histone variants.
AB  - In eukaryotes, DNA is organized into chromatin, a dynamic structure that enables
      DNA to be accessed for processes such as transcription, replication and repair.
      To form, maintain or alter this organization according to cellular needs,
      histones, the main protein component of chromatin, are deposited, replaced,
      exchanged and post-translationally modified. Histone variants, which exhibit
      specialized deposition modes in relation to the cell cycle and possibly
      particular chromatin regions, add an additional level of complexity in the
      regulation of histone flow. During their metabolism, from their synthesis to
      their delivery for nucleosome formation, the histones are escorted by proteins
      called histone chaperones. In the present chapter we summarize our current
      knowledge concerning histone chaperones and their interaction with particular
      histones based on key structural properties. From a compilation of selected
      histone chaperones identified to date, we discuss how they may be placed in a
      network to regulate histone dynamics. Finally, we provide working models to
      explain how H3 variants, deposited on to DNA using different histone chaperone
      machineries, can be transmitted or lost through cell divisions.

PMID- 20822488
TI  - RNA-directed epigenetic regulation of DNA rearrangements.
AB  - Ciliated protozoa undergo extensive DNA rearrangements, including DNA
      elimination, chromosome breakage and DNA unscrambling, when the germline
      micronucleus produces the new macronucleus during sexual reproduction. It has
      long been known that many of these events are epigenetically controlled by DNA
      sequences of the parental macronuclear genome. Recent studies in some model
      ciliates have revealed that these epigenetic regulations are mediated by non
      coding RNAs. DNA elimination in Paramecium and Tetrahymena is regulated by small
      RNAs that are produced and operated by an RNAi (RNA interference)-related
      mechanism. It has been proposed that the small RNAs from the micronuclear genome
      can be used to identify eliminated DNAs by whole-genome comparison of the
      parental macronucleus and the micronucleus. In contrast, DNA unscrambling in
      Oxytricha is guided by long non-coding RNAs that are produced from the somatic
      parental macronuclear genome. These RNAs are proposed to act as templates for the
      direct unscrambling events that occur in the developing macronucleus. The
      possible evolutionary benefits of these RNA-directed epigenetic regulations of
      DNA rearrangement in ciliates are discussed in the present chapter.

PMID- 20822489
TI  - Non-Mendelian epigenetic heredity: gametic RNAs as epigenetic regulators and
      transgenerational signals.
AB  - Inheritance of epigenetic variations may account for a significant part of
      heritability in human and in mammalian models. Heritable epigenetic variations
      were reported in plants under the name 'paramutation' more than 50 years ago.
      Reports by E. Whitelaw and her colleagues and by our laboratory now describe a
      variety of situations resulting in epigenetic inheritance in mouse systems. In
      the three cases that we have analysed, a transcriptional increase is initiated by
      RNAs related to the locus, either microRNAs or transcript fragments. RNAs carried
      by the spermatozoon appear as the transgenerational signals responsible for
      paternal transmission. Extension from mouse models to human heredity, obviously
      speculative at present, is encouraged by the high load of RNA in human sperm.

PMID- 20822490
TI  - Epigenetic dynamics across the cell cycle.
AB  - Progression of the mammalian cell cycle depends on correct timing and co
      ordination of a series of events, which are managed by the cellular
      transcriptional machinery and epigenetic mechanisms governing genome
      accessibility. Epigenetic chromatin modifications are dynamic across the cell
      cycle, and are shown to influence and be influenced by cell-cycle progression.
      Chromatin modifiers regulate cell-cycle progression locally by controlling the
      expression of individual genes and globally by controlling chromatin condensation
      and chromosome segregation. The cell cycle, on the other hand, ensures a correct
      inheritance of epigenetic chromatin modifications to daughter cells. In this
      chapter, we summarize the current knowledge on the dynamics of epigenetic
      chromatin modifications during progression of the cell cycle.

PMID- 20822491
TI  - Epigenetic regulation of cell life and death decisions and deregulation in
      cancer.
AB  - For every cell, there is a time to live and a time to die. It is apparent that
      cell life and death decisions are taken by individual cells based on their
      interpretation of physiological or non-physiological stimuli, or their own self
      assessment of internal damage or changes in their environment. Apoptosis or
      programmed cell death is a key regulator of physiological growth control and
      regulation of tissue homoeostasis. One of the most important advances in cancer
      research in recent years is the recognition that cell death, mostly by apoptosis,
      is crucially involved in the regulation of tumour formation and also critically
      determines treatment response. The initiation and progression of cancer,
      traditionally seen as a genetic disease, is now realized to involve epigenetic
      abnormalities along with genetic alterations. The study of epigenetic mechanisms
      in cancer, such as DNA methylation, histone modifications and microRNA
      expression, has revealed a plethora of events that contribute to the neoplastic
      phenotype through stable changes in the expression of genes critical to cell
      death pathways. A better understanding of the epigenetic molecular events that
      regulate apoptosis, together with the reversible nature of epigenetic
      aberrations, should contribute to the emergence of the promising field of
      epigenetic therapy.

PMID- 20822492
TI  - Dynamics of telomeric chromatin at the crossroads of aging and cancer.
AB  - Telomeres are nucleoprotein structures that protect the ends of human chromosomes
      through the formation of a 'cap', thus preventing exonucleolytic degradation,
      inter- and intra-chromosomal fusion, and subsequent chromosomal instability.
      During aging, telomere shortening correlates with tissue dysfunction and loss of
      renewal capacity. In human cancer, telomere dysfunction is involved in early
      chromosome instability, long-term cellular proliferation, and possibly other
      processes related to cell survival and microenvironment. Telomeres constitute an
      attractive target for the development of novel small-molecule anti-cancer drugs.
      In particular, individual protein components of the core telomere higher-order
      chromatin structure (known as the telosome or 'shelterin' complex) are promising
      candidate targets for cancer therapy.

PMID- 20822493
TI  - MicroRNAs, epigenetics and disease.
AB  - Epigenetics is defined as the heritable chances that affect gene expression
      without changing the DNA sequence. Epigenetic regulation of gene expression can
      be through different mechanisms such as DNA methylation, histone modifications
      and nucleosome positioning. MicroRNAs are short RNA molecules which do not code
      for a protein but have a role in post-transcriptional silencing of multiple
      target genes by binding to their 3' UTRs (untranslated regions). Both epigenetic
      mechanisms, such as DNA methylation and histone modifications, and the microRNAs
      are crucial for normal differentiation, development and maintenance of tissue
      specific gene expression. These mechanisms also explain how cells with the same
      DNA content can differentiate into cells with different functions. Changes in
      epigenetic processes can lead to changes in gene function, cancer formation and
      progression, as well as other diseases. In the present chapter we will mainly
      focus on microRNAs and methylation and their implications in human disease,
      mainly in cancer.

PMID- 20822494
TI  - Genomic imprinting and human disease.
AB  - In many epigenetic phenomena, covalent modifications on DNA and chromatin mediate
      somatically heritable patterns of gene expression. Genomic imprinting is a
      classical example of epigenetic regulation in mammals. To date, more than 100
      imprinted genes have been identified in humans and mice. Many of these are
      involved in foetal growth and deve lopment, others control behaviour. Mono
      allelic expression of imprinted genes depends on whether the gene is inherited
      from the mother or the father. This remarkable pattern of expression is
      controlled by specialized sequence elements called ICRs (imprinting control
      regions). ICRs are marked by DNA methylation on one of the two parental alleles.
      These allelic marks originate from either the maternal or the paternal germ line.
      Perturbation of the allelic DNA methylation at ICRs is causally involved in
      several human diseases, including the Beckwith-Wiedemann and Silver-Russell
      syndromes, associated with aberrant foetal growth. Perturbed imprinted gene
      expression is also implicated in the neuro-developmental disorders Prader-Willi
      syndrome and Angelman syndrome. Embryo culture and human-assisted reproduction
      procedures can increase the occurrence of imprinting-related disorders. Recent
      research shows that, besides DNA methylation, covalent histone modifications and
      non-histone proteins also contribute to imprinting regulation. The involvement of
      imprinting in specific human pathologies (and in cancer) emphasizes the need to
      further explore the underlying molecular mechanisms.

PMID- 20822495
TI  - Epigenetics and transcriptional control in African trypanosomes.
AB  - The African trypanosome Trypanosoma brucei is a unicellular parasite which causes
      African sleeping sickness. Transcription in African trypanosomes displays some
      unusual features, as most of the trypanosome genome is transcribed as extensive
      polycistronic RNA Pol II (polymerase II) transcription units that are not
      transcriptionally regulated. In addition, RNA Pol I is used for transcription of
      a small subset of protein coding genes in addition to the rDNA (ribosomal DNA).
      These Pol I-transcribed protein coding genes include the VSG (variant surface
      glycoprotein) genes. Although a single trypanosome has many hundreds of VSG
      genes, the active VSG is transcribed in a strictly monoalleleic fashion from one
      of approx. 15 telomeric VSG ESs (expression sites). Originally, it was thought
      that chromatin was not involved in the transcriptional control of ESs; however,
      this view is now being re-evaluated. It has since been shown that the active ES
      is depleted of nucleosomes compared with silent ESs. In addition, a number of
      proteins involved in chromatin remodelling or histone modification and which play
      a role in ES silencing {including TbISWI [T. brucei ISWI (imitation-switch
      protein)] and DOT1B} have recently been identified. Lastly, the telomere-binding
      protein TbRAP1 (T. brucei RAP1) has been shown to establish a repressive gradient
      extending from the ES telomere end up to the ES promoter. We still need to
      determine which epigenetic factors are involved in 'marking' the active ES as
      part of the counting mechanism of monoallelic exclusion. The challenge will come
      in determining how these multiple regulatory layers contribute to ES control.

PMID- 20822496
TI  - Epigenetic regulation of V(D)J recombination.
AB  - Chromosome breaks are dangerous business, carrying the risk of loss of genetic
      information or, even worse, misrepair of the break, leading to outcomes such as
      dicentric chromosomes or oncogenic translocations. Yet V(D)J recombination, a
      process that breaks, rearranges and repairs chromosomes, is crucial to the
      development of the adaptive immune system, for it gives B- and T-cells the
      capacity to generate a virtually unlimited repertoire of antigen receptor
      proteins to combat an equally vast array of antigens. To minimize the risks
      inherent in chromosomal breakage, V(D)J recombination is carefully orchestrated
      at multiple levels, ranging from DNA sequence requirements all the way up to
      chromatin conformation and nuclear architecture. In the present chapter we
      introduce various regulatory controls, with an emphasis on epigenetic mechanisms
      and recent work that has begun to elucidate their interdependence.

PMID- 20822497
TI  - Chromatin plasticity in pluripotent cells.
AB  - ESCs (embryonic stem cells), derived from the blastocyst stage embryo, are
      characterized by an indefinite ability for self-renewal as well as pluripotency,
      enabling them to differentiate into all cell types of the three germ layers. In
      the undifferentiated state, ESCs display a global promiscuous transcriptional
      programme which is restricted gradually upon differentiation. Supporting
      transcriptional promiscuity, chromatin in pluripotent cells is more 'plastic' or
      'open', with decondensed heterochromatin architecture, enrichment of active
      histone modifications, and a hyperdynamic association of chromatin proteins with
      chromatin. During ESC differentiation, nuclear architecture and chromatin undergo
      substantial changes. Heterochromatin foci appear smaller, more numerous and more
      condensed in the differentiated state, the nuclear lamina becomes more defined
      and chromatin protein dynamics becomes restricted. In the present chapter we
      discuss chromatin plasticity and epigenetics and the mechanisms that regulate the
      various chromatin states, which are currently a central theme in the studies of
      stem cell maintenance and differentiation, and which will no doubt assist in
      delineating the secrets of pluripotency and self-renewal.

PMID- 20822498
TI  - Epigenetic regulation of genes in learning and memory.
AB  - Rapid advances in the field of epigenetics are revealing a new way to understand
      how we can form and store strong memories of significant events in our lives.
      Epigenetic modifications of chromatin, namely the post-translational
      modifications of nuclear proteins and covalent modification of DNA that regulate
      gene activity in the CNS (central nervous system), continue to be recognized for
      their pivotal role in synaptic plasticity and memory formation. At the same time,
      studies are correlating aberrant epigenetic regulation of gene activity with
      cognitive dysfunction prevalent in CNS disorders and disease. Epigenetic
      research, then, offers not only a novel approach to understanding the molecular
      transcriptional mechanisms underlying experience-induced changes in neural
      function and behaviour, but potential therapeutic treatments aimed at alleviating
      cognitive dysfunction. In this chapter, we discuss data regarding epigenetic
      marking of genes in adult learning and memory formation and impairment thereof,
      as well as data showcasing the promise for manipulating the epigenome in
      restoring memory capacity.

PMID- 20822499
TI  - Environmental epigenomics: understanding the effects of parental care on the
      epigenome.
AB  - An organism's behavioural and physiological and social milieu influence and are
      influenced by the epigenome, which is comprised predominantly of chromatin and
      the covalent modification of DNA by methylation. Epigenetic patterns are sculpted
      during development to shape the diversity of gene expression programmes in the
      organism. In contrast with the genetic sequence, which is determined by
      inheritance and is virtually identical in all tissues, the epigenetic pattern
      varies from cell type to cell type and is potentially dynamic throughout life. It
      is postulated that different environmental exposures could effect epigenetic
      patterns relevant for human behaviour. Because epigenetic programming defines the
      state of expression of genes, epigenetic differences could have the same
      consequences as genetic polymorphisms. Yet in contrast with genetic sequence
      differences, epigenetic alterations are potentially reversible. In the present
      chapter, we will discuss evidence that epigenetic processes early in life play a
      role in defining inter-individual trajectories of behaviour, with implications
      for mental health in adulthood.

PMID- 20822500
TI  - Clinical trial: oral zinc in hepatic encephalopathy.
AB  - BACKGROUND: Hepatic encephalopathy has a negative effect on patient health
      related quality of life (HRQOL). Zinc supplementation has been effective with
      regard to altered nitrogen metabolism. AIM: To investigate the effectiveness of
      oral zinc supplementation on hepatic encephalopathy and HRQOL. METHODS: Seventy
      nine cirrhotic patients with hepatic encephalopathy were randomized to receive
      225 mg of polaprezinc in addition to standard therapies of a protein-restricted
      diet including branched-chain amino acid and lactulose, or to continue only
      standard therapies for 6 months. The change of HRQOL by Short Form-36, hepatic
      encephalopathy grade, laboratory parameters, and neuropsychological (NP) tests
      were compared at baseline and at 6 months. We also evaluated via multivariate
      analysis whether zinc supplementation and clinical variables correlated with the
      changes in physical component scale (PCS) and mental component scale (MCS)
      between the two visits. RESULTS: Zinc supplementation significantly improved the
      PCS (P = 0.04), but not the MCS (P = 0.95). Zinc supplementation significantly
      decreased hepatic encephalopathy grade and blood ammonia levels (P = 0.03 and P =
      0.01), and improved Child-Pugh score and NP tests compared with standard therapy
      (P = 0.04 and P = 0.02). In multivariate analysis, zinc supplementation was
      significantly associated with improvement in PCS (P = 0.03), whereas it was not
      significantly associated with change in MCS (P = 0.98). CONCLUSION: Zinc
      supplementation is effective in hepatic encephalopathy and consequently improves
      patients HRQOL.

PMID- 20822501
TI  - De-regulation of abscisic acid contents causes abnormal endosperm development in
      the barley mutant seg8.
AB  - Grain development of the maternal effect shrunken endosperm mutant seg8 was
      analysed by comprehensive molecular, biochemical and histological methods. The
      most obvious finding was de-regulation of ABA levels, which were lower compared
      to wild-type during the pre-storage phase but higher during the transition from
      cell division/differentiation to accumulation of storage products. Ploidy levels
      and ABA amounts were inversely correlated in the developing endosperms of both
      mutant and wild-type, suggesting an influence of ABA on cell-cycle regulation.
      The low ABA levels found in seg8 grains between anthesis and beginning endosperm
      cellularization may result from a gene dosage effect in the syncytial endosperm
      that causes impaired transfer of ABA synthesized in vegetative tissues into
      filial grain parts. Increased ABA levels during the transition phase are
      accompanied by higher chlorophyll and carotenoid/xanthophyll contents. The data
      suggest a disturbed ABA-releasing biosynthetic pathway. This is indicated by up
      regulation of expression of the geranylgeranyl reductase (GGR) gene, which may be
      induced by ABA deficiency during the pre-storage phase. Abnormal
      cellularization/differentiation of the developing seg8 endosperm and reduced
      accumulation of starch are phenotypic characteristics that reflect these
      disturbances. The present study did not reveal the primary gene defect causing
      the seg8 phenotype, but presents new insights into the maternal/filial
      relationships regulating barley endosperm development.

PMID- 20822502
TI  - Biological implications of the occurrence of 32 members of the XTH (xyloglucan
      endotransglucosylase/hydrolase) family of proteins in the bryophyte
      Physcomitrella patens.
AB  - This comprehensive overview of the xyloglucan endotransglucosylase/hydrolase
      (XTH) family of genes and proteins in bryophytes, based on research using genomic
      resources that are newly available for the moss Physcomitrella patens, provides
      new insights into plant evolution. In angiosperms, the XTH genes are found in
      large multi-gene families, probably reflecting the diverse roles of individual
      XTHs in various cell types. As there are fewer cell types in P. patens than in
      angiosperms such as Arabidopsis and rice, it is tempting to deduce that there are
      fewer XTH family genes in bryophytes. However, the present study unexpectedly
      identified as many as 32 genes that potentially encode XTH family proteins in the
      genome of P. patens, constituting a fairly large multi-gene family that is
      comparable in size with those of Arabidopsis and rice. In situ localization of
      xyloglucan endotransglucosylase activity in this moss indicates that some P.
      patens XTH proteins exhibit biochemical functions similar to those found in
      angiosperms, and that their expression profiles are tissue-dependent. However,
      comparison of structural features of families of XTH genes between P. patens and
      angiosperms demonstrated the existence of several bryophyte-specific XTH genes
      with distinct structural and functional features that are not found in
      angiosperms. These bryophyte-specific XTH genes might have evolved to meet
      morphological and functional needs specific to the bryophyte. These findings
      raise interesting questions about the biological implications of the XTH family
      of proteins in non-seed plants.

PMID- 20822503
TI  - The Arabidopsis vacuolar anion transporter, AtCLCc, is involved in the regulation
      of stomatal movements and contributes to salt tolerance.
AB  - In plant cells, anion channels and transporters are essential for key functions
      such as nutrition, resistance to biotic or abiotic stresses, and ion homeostasis.
      In Arabidopsis, members of the chloride channel (CLC) family located in
      intracellular organelles have been shown to be required for nitrate homeostasis
      or pH adjustment, and previous results indicated that AtCLCc is involved in
      nitrate accumulation. We investigated new physiological functions of this CLC
      member in Arabidopsis. Here we report that AtCLCc is strongly expressed in guard
      cells and pollen and more weakly in roots. Use of an AtCLCc:GFP fusion revealed
      localization to the tonoplast. Disruption of the AtCLCc gene by a T-DNA insertion
      in four independent lines affected physiological responses that are directly
      related to the movement of chloride across the tonoplast membrane. Opening of
      clcc stomata was reduced in response to light, and ABA treatment failed to induce
      their closure, whereas application of KNO3 but not KCl restored stomatal opening.
      clcc mutant plants were hypersensitive to NaCl treatment when grown on soil, and
      to NaCl and KCl in vitro, confirming the chloride dependence of the phenotype.
      These phenotypes were associated with modifications of chloride content in both
      guard cells and roots. These data demonstrate that AtCLCc is essential for
      stomatal movement and salt tolerance by regulating chloride homeostasis.

PMID- 20822504
TI  - Engineering traditional monolignols out of lignin by concomitant up-regulation of
      F5H1 and down-regulation of COMT in Arabidopsis.
AB  - Lignin engineering is a promising strategy to optimize lignocellulosic plant
      biomass for use as a renewable feedstock for agro-industrial applications.
      Current efforts focus on engineering lignin with monomers that are not normally
      incorporated into wild-type lignins. Here we describe an Arabidopsis line in
      which the lignin is derived to a major extent from a non-traditional monomer. The
      combination of mutation in the gene encoding caffeic acid O-methyltransferase
      (comt) with over-expression of ferulate 5-hydroxylase under the control of the
      cinnamate 4-hydroxylase promoter (C4H:F5H1) resulted in plants with a unique
      lignin comprising almost 92% benzodioxane units. In addition to biosynthesis of
      this particular lignin, the comt C4H:F5H1 plants revealed massive shifts in
      phenolic metabolism compared to the wild type. The structures of 38 metabolites
      that accumulated in comt C4H:F51 plants were resolved by mass spectral analyses,
      and were shown to derive from 5-hydroxy-substituted phenylpropanoids. These
      metabolites probably originate from passive metabolism via existing biochemical
      routes normally used for 5-methoxylated and 5-unsubstituted phenylpropanoids and
      from active detoxification by hexosylation. Transcripts of the phenylpropanoid
      biosynthesis pathway were highly up-regulated in comt C4H:F5H1 plants, indicating
      feedback regulation within the pathway. To investigate the role of flavonoids in
      the abnormal growth of comt C4H:F5H1 plants, a mutation in a gene encoding
      chalcone synthase (chs) was crossed in. The resulting comt C4H:F5H1 chs plants
      showed partial restoration of growth. However, a causal connection between
      flavonoid deficiency and this restoration of growth was not demonstrated;
      instead, genetic interactions between phenylpropanoid and flavonoid biosynthesis
      could explain the partial restoration. These genetic interactions must be taken
      into account in future cell-wall engineering strategies.

PMID- 20822505
TI  - OsMADS6 plays an essential role in endosperm nutrient accumulation and is subject
      to epigenetic regulation in rice (Oryza sativa).
AB  - MADS-box transcription factors are known for their roles in plant growth and
      development. The regulatory mechanisms of spatial and temporal specific
      expression of MADS-box genes and the function of MADS-box genes in other
      biological processes are still to be explored. Here, we report that OsMADS6 is
      highly expressed in flower and endosperm in Oryza sativa (rice). In addition to
      displaying a homeotic organ identity phenotype in all the four whorls of the
      flowers, the endosperm development is severely affected in its mutant. At least
      32% of the seeds lacked starch filling and aborted. For seeds that have starch
      filling and develop to maturity, the starch content is reduced by at least 13%.
      In addition, the seed shape changes from elliptical to roundish, and the protein
      content increases from 12.1 to 15.0% (P < 0.05). Further investigation shows that
      ADP-glucose pyrophosphorylase genes, encoding the rate-limiting step enzyme in
      the starch synthesis pathway, are subject to the regulation of OsMADS6. Chromatin
      immunoprecipitation (ChIP)-PCR analyses on the chromatin of the OsMADS6 gene find
      that H3K27 is trimethylated in tissues where OsMADS6 is silenced, and that H3K36
      is trimethylated in tissues where OsMADS6 is highly activated. Point mutation
      analysis reveals that leucine at position 83 is critical to OsMADS6 function.

PMID- 20822506
TI  - A large proportion of asymptomatic Plasmodium infections with low and sub
      microscopic parasite densities in the low transmission setting of Temotu
      Province, Solomon Islands: challenges for malaria diagnostics in an elimination
      setting.
AB  - BACKGROUND: Many countries are scaling up malaria interventions towards
      elimination. This transition changes demands on malaria diagnostics from
      diagnosing ill patients to detecting parasites in all carriers including
      asymptomatic infections and infections with low parasite densities. Detection
      methods suitable to local malaria epidemiology must be selected prior to
      transitioning a malaria control programme to elimination. A baseline malaria
      survey conducted in Temotu Province, Solomon Islands in late 2008, as the first
      step in a provincial malaria elimination programme, provided malaria epidemiology
      data and an opportunity to assess how well different diagnostic methods performed
      in this setting. METHODS: During the survey, 9,491 blood samples were collected
      and examined by microscopy for Plasmodium species and density, with a subset also
      examined by polymerase chain reaction (PCR) and rapid diagnostic tests (RDTs).
      The performances of these diagnostic methods were compared. RESULTS: A total of
      256 samples were positive by microscopy, giving a point prevalence of 2.7%. The
      species distribution was 17.5% Plasmodium falciparum and 82.4% Plasmodium vivax.
      In this low transmission setting, only 17.8% of the P. falciparum and 2.9% of P.
      vivax infected subjects were febrile (>= 38 degrees C) at the time of the survey.
      A significant proportion of infections detected by microscopy, 40% and 65.6% for
      P. falciparum and P. vivax respectively, had parasite density below 100/MUL.
      There was an age correlation for the proportion of parasite density below 100/MUL
      for P. vivax infections, but not for P. falciparum infections. PCR detected
      substantially more infections than microscopy (point prevalence of 8.71%),
      indicating a large number of subjects had sub-microscopic parasitemia. The
      concordance between PCR and microscopy in detecting single species was greater
      for P. vivax (135/162) compared to P. falciparum (36/118). The malaria RDT
      detected the 12 microscopy and PCR positive P. falciparum, but failed to detect
      12/13 microscopy and PCR positive P. vivax infections. CONCLUSION: Asymptomatic
      malaria infections and infections with low and sub-microscopic parasite densities
      are highly prevalent in Temotu province where malaria transmission is low. This
      presents a challenge for elimination since the large proportion of the parasite
      reservoir will not be detected by standard active and passive case detection.
      Therefore effective mass screening and treatment campaigns will most likely need
      more sensitive assays such as a field deployable molecular based assay.

PMID- 20822507
TI  - Epidemiological study of phylogenetic transmission clusters in a local HIV-1
      epidemic reveals distinct differences between subtype B and non-B infections.
AB  - BACKGROUND: The number of HIV-1 infected individuals in the Western world
      continues to rise. More in-depth understanding of regional HIV-1 epidemics is
      necessary for the optimal design and adequate use of future prevention
      strategies. The use of a combination of phylogenetic analysis of HIV sequences,
      with data on patients' demographics, infection route, clinical information and
      laboratory results, will allow a better characterization of individuals
      responsible for local transmission. METHODS: Baseline HIV-1 pol sequences,
      obtained through routine drug-resistance testing, from 506 patients, newly
      diagnosed between 2001 and 2009, were used to construct phylogenetic trees and
      identify transmission-clusters. Patients' demographics, laboratory and clinical
      data, were retrieved anonymously. Statistical analysis was performed to identify
      subtype-specific and transmission-cluster-specific characteristics. RESULTS:
      Multivariate analysis showed significant differences between the 59.7% of
      individuals with subtype B infection and the 40.3% non-B infected individuals,
      with regard to route of transmission, origin, infection with Chlamydia (p = 0.01)
      and infection with Hepatitis C virus (p = 0.017). More and larger transmission
      clusters were identified among the subtype B infections (p < 0.001). Overall, in
      multivariate analysis, clustering was significantly associated with Caucasian
      origin, infection through homosexual contact and younger age (all p < 0.001).
      Bivariate analysis additionally showed a correlation between clustering and
      syphilis (p < 0.001), higher CD4 counts (p = 0.002), Chlamydia infection (p =
      0.013) and primary HIV (p = 0.017). CONCLUSIONS: Combination of phylogenetics
      with demographic information, laboratory and clinical data, revealed that HIV-1
      subtype B infected Caucasian men-who-have-sex-with-men with high prevalence of
      sexually transmitted diseases, account for the majority of local HIV
      transmissions. This finding elucidates observed epidemiological trends through
      molecular analysis, and justifies sustained focus in prevention on this high risk
      group.

PMID- 20822508
TI  - Association between CETP Taq1B and LIPC -514C/T polymorphisms with the serum
      lipid levels in a group of Tehran's population: a cross sectional study.
AB  - BACKGROUND: Low level of high density lipoprotein cholesterol (HDL-C) has high
      prevalence in the Tehran Lipid and Glucose Study (TLGS) cohort. About 50% of the
      inter-individual variation in serum HDL-C levels is genetically determined.
      Polymorphisms in cholesteryl ester transfer protein (CETP) and hepatic lipase
      (LIPC) genes have been found to be associated with the metabolism and serum
      concentration of the HDL-C. OBJECTIVES: To determine the association between
      Taq1B polymorphism in CETP gene and -514C/T polymorphism in LIPC gene with serum
      lipid levels and lipid peroxidation in a subgroup of the TLGS population.
      RESULTS: Serum HDL-C level had significant association with CETP Taq1B
      polymorphism and B2B2 subjects had the highest HDL-C levels compared to B2B1 and
      B1B1 genotypes (37.9 vs. 36.9 and 35.3 mg/dl, respectively; P = 0.01). However,
      carriers of "B1" allele, in comparison to the non carriers (B2B2), had
      significantly lower levels of TC (200.1 vs. 215.2 mg/dl; P = 0.005), HDL-C (35.8
      vs. 37.9 mg/dl; P = 0.009) and malondialdehyde MDA (4.5 vs. 5.0 nmol/mL;
      P=0.031). Carriers of the "T" allele in -514C/T polymorphism in LIPC gene had
      higher means of HDL-C than non carriers (37.7 vs. 35.7 mg/dl, P = 0.04). No other
      association was found between -514C/T polymorphism and any other serum lipids or
      MDA level. CONCLUSION: This study demonstrates the association between Taq1B and 
      514C/T polymorphisms in the CETP and LIPC genes with the serum HDL-C levels.

PMID- 20822509
TI  - Sequential introduction of single room isolation and hand hygiene campaign in the
      control of methicillin-resistant Staphylococcus aureus in intensive care unit.
AB  - BACKGROUND: After renovation of the adult intensive care unit (ICU) with
      installation of ten single rooms, an enhanced infection control program was
      conducted to control the spread of methicillin-resistant Staphylococcus aureus
      (MRSA) in our hospital. METHODS: Since the ICU renovation, all patients colonized
      or infected with MRSA were nursed in single rooms with contact precautions. The
      incidence of MRSA infection in the ICU was monitored during 3 different phases:
      the baseline period (phase 1); after ICU renovation (phase 2) and after
      implementation of a hand hygiene campaign with alcohol-based hand rub (phase 3).
      Patients infected with extended spectrum beta-lactamase (ESBL)-producing
      Escherichia coli and Klebsiella species were chosen as controls because they were
      managed in open cubicles with standard precautions. RESULTS: Without a major
      change in bed occupancy rate, nursing workforce, or the protocol of environmental
      cleansing throughout the study period, a stepwise reduction in ICU onset
      nonbacteraemic MRSA infection was observed: from 3.54 (phase 1) to 2.26 (phase 2,
      p = 0.042) and 1.02 (phase 3, p = 0.006) per 1000-patient-days. ICU onset
      bacteraemic MRSA infection was significantly reduced from 1.94 (phase 1) to 0.9
      (phase 2, p = 0.005) and 0.28 (phase 3, p = 0.021) per 1000-patient-days.
      Infection due to ESBL-producing organisms did not show a corresponding reduction.
      The usage density of broad-spectrum antibiotics and fluoroquinolones increased
      from phase 1 to 3. However a significant trend improvement of ICU onset MRSA
      infection by segmented regression analysis can only be demonstrated when
      comparison was made before and after the severe acute respiratory syndrome (SARS)
      epidemic. This suggests that the deaths of fellow healthcare workers from an
      occupational acquired infection had an overwhelming effect on their compliance
      with infection control measures. CONCLUSION: Provision of single room isolation
      facilities and promotion of hand hygiene practice are important. However
      compliance with infection control measures relies largely on a personal
      commitment, which may increase when personal safety is threatened.

PMID- 20822510
TI  - Global regulation of gene expression in response to cysteine availability in
      Clostridium perfringens.
AB  - BACKGROUND: Cysteine has a crucial role in cellular physiology and its synthesis
      is tightly controlled due to its reactivity. However, little is known about the
      sulfur metabolism and its regulation in clostridia compared with other
      firmicutes. In Clostridium perfringens, the two-component system, VirR/VirS,
      controls the expression of the ubiG operon involved in methionine to cysteine
      conversion in addition to the expression of several toxin genes. The existence of
      links between the C. perfringens virulence regulon and sulfur metabolism prompted
      us to analyze this metabolism in more detail. RESULTS: We first performed a
      tentative reconstruction of sulfur metabolism in C. perfringens and correlated
      these data with the growth of strain 13 in the presence of various sulfur
      sources. Surprisingly, C. perfringens can convert cysteine to methionine by an
      atypical still uncharacterized pathway. We further compared the expression
      profiles of strain 13 after growth in the presence of cystine or homocysteine
      that corresponds to conditions of cysteine depletion. Among the 177 genes
      differentially expressed, we found genes involved in sulfur metabolism and
      controlled by premature termination of transcription via a cysteine specific T
      box system (cysK-cysE, cysP1 and cysP2) or an S-box riboswitch (metK and metT).
      We also showed that the ubiG operon was submitted to a triple regulation by
      cysteine availability via a T-box system, by the VirR/VirS system via the VR-RNA
      and by the VirX regulatory RNA.In addition, we found that expression of pfoA
      (theta-toxin), nagL (one of the five genes encoding hyaluronidases) and genes
      involved in the maintenance of cell redox status was differentially expressed in
      response to cysteine availability. Finally, we showed that the expression of
      genes involved in [Fe-S] clusters biogenesis and of the ldh gene encoding the
      lactate dehydrogenase was induced during cysteine limitation. CONCLUSION: Several
      key functions for the cellular physiology of this anaerobic bacterium were
      controlled in response to cysteine availability. While most of the genes involved
      in sulfur metabolism are regulated by premature termination of transcription,
      other still uncharacterized mechanisms of regulation participated in the
      induction of gene expression during cysteine starvation.

PMID- 20822511
TI  - Mechanisms underlying dioxygen reduction in laccases. Structural and modelling
      studies focusing on proton transfer.
AB  - BACKGROUND: Laccases are enzymes that couple the oxidation of substrates with the
      reduction of dioxygen to water. They are the simplest members of the multi-copper
      oxidases and contain at least two types of copper centres; a mononuclear T1 and a
      trinuclear that includes two T3 and one T2 copper ions. Substrate oxidation takes
      place at the mononuclear centre whereas reduction of oxygen to water occurs at
      the trinuclear centre. RESULTS: In this study, the CotA laccase from Bacillus
      subtilis was used as a model to understand the mechanisms taking place at the
      molecular level, with a focus in the trinuclear centre. The structures of the
      holo-protein and of the oxidised form of the apo-protein, which has previously
      been reconstituted in vitro with Cu(I), have been determined. The former has a
      dioxygen moiety between the T3 coppers, while the latter has a monoatomic oxygen,
      here interpreted as a hydroxyl ion. The UV/visible spectra of these two forms
      have been analysed in the crystals and compared with the data obtained in
      solution. Theoretical calculations on these and other structures of CotA were
      used to identify groups that may be responsible for channelling the protons that
      are needed for reduction of dioxygen to water. CONCLUSIONS: These results present
      evidence that Glu 498 is the only proton-active group in the vicinity of the
      trinuclear centre. This strongly suggests that this residue may be responsible
      for channelling the protons needed for the reduction. These results are compared
      with other data available for these enzymes, highlighting similarities and
      differences within laccases and multicopper oxidases.

PMID- 20822512
TI  - Sequencing and analysis of an Irish human genome.
AB  - BACKGROUND: Recent studies generating complete human sequences from Asian,
      African and European subgroups have revealed population-specific variation and
      disease susceptibility loci. Here, choosing a DNA sample from a population of
      interest due to its relative geographical isolation and genetic impact on further
      populations, we extend the above studies through the generation of 11-fold
      coverage of the first Irish human genome sequence. RESULTS: Using sequence data
      from a branch of the European ancestral tree as yet unsequenced, we identify
      variants that may be specific to this population. Through comparisons with HapMap
      and previous genetic association studies, we identified novel disease-associated
      variants, including a novel nonsense variant putatively associated with
      inflammatory bowel disease. We describe a novel method for improving SNP calling
      accuracy at low genome coverage using haplotype information. This analysis has
      implications for future re-sequencing studies and validates the imputation of
      Irish haplotypes using data from the current Human Genome Diversity Cell Line
      Panel (HGDP-CEPH). Finally, we identify gene duplication events as constituting
      significant targets of recent positive selection in the human lineage.
      CONCLUSIONS: Our findings show that there remains utility in generating whole
      genome sequences to illustrate both general principles and reveal specific
      instances of human biology. With increasing access to low cost sequencing we
      would predict that even armed with the resources of a small research group a
      number of similar initiatives geared towards answering specific biological
      questions will emerge.

PMID- 20822513
TI  - Immunosenescence and Cytomegalovirus: where do we stand after a decade?

PMID- 20822514
TI  - Reciprocal control of cell proliferation and migration.
AB  - In adult tissue the quiescent state of a single cell is maintained by the steady
      state conditions of its own microenvironment for what concern both cell-cell as
      well as cell-ECM interaction and soluble factors concentration. Physiological or
      pathological conditions can alter this quiescent state through an imbalance of
      both soluble and insoluble factors that can trigger a cellular phenotypic
      response. The kind of cellular response depends by many factors but one of the
      most important is the concentration of soluble cytokines sensed by the target
      cell. In addition, due to the intrinsic plasticity of many cellular types, every
      single cell is able, in response to the same stimulus, to rapidly switch
      phenotype supporting minimal changes of microenviromental cytokines
      concentration. Wound healing is a typical condition in which epithelial,
      endothelial as well as mesenchymal cells are firstly subjected to activation of
      their motility in order to repopulate the damaged region and then they show a
      strong proliferative response in order to successfully complete the wound repair
      process. This schema constitute the leitmotif of many other physiological or
      pathological conditions such as development vasculogenesis/angiogenesis as well
      as cancer outgrowth and metastasis.Our review focuses on the molecular mechanisms
      that control the starting and, eventually, the switching of cellular phenotypic
      outcome in response to changes in the symmetry of the extracellular environment.

PMID- 20822515
TI  - Aquaporin-4 autoantibodies in neuromyelitis optica spectrum disorders: comparison
      between tissue-based and cell-based indirect immunofluorescence assays.
AB  - BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are severe central
      nervous system inflammatory demyelinating disorders (CNS IDD) characterized by
      monophasic or relapsing, longitudinally extensive transverse myelitis (LETM)
      and/or optic neuritis (ON). A significant proportion of NMOSD patients are
      seropositive for aquaporin-4 (AQP4) autoantibodies. We compared the AQP4
      autoantibody detection rates of tissue-based indirect immunofluorescence assay
      (IIFA) and cell-based IIFA. METHODS: Serum of Chinese CNS IDD patients were
      assayed for AQP4 autoantibodies by tissue-based IIFA using monkey cerebellum and
      cell-based IIFA using transfected HEK293 cells which express human AQP4 on their
      cell membranes. RESULTS: In total, 128 CNS IDD patients were studied. We found
      that 78% of NMO patients were seropositive for AQP4 autoantibodies by cell-based
      IIFA versus 61% by tissue-based IFA (p = 0.250), 75% of patients having relapsing
      myelitis (RM) with LETM were seropositive by cell-based IIFA versus 50% by tissue
      based IIFA (p = 0.250), and 33% of relapsing ON patients were seropositive by
      cell-based IIFA versus 22% by tissue-based IIFA (p = 1.000); however the
      differences were not statistically significant. All patients seropositive by
      tissue-based IIFA were also seropositive for AQP4 autoantibodies by cell-based
      IIFA. Among 29 NMOSD patients seropositive for AQP4 autoantibodies by cell-based
      IIFA, 20 (69%) were seropositive by tissue-based IIFA. The 9 patients
      seropositive by cell-based IIFA while seronegative by tissue-based IIFA had NMO
      (3), RM with LETM (3), a single attack of LETM (1), relapsing ON (1) and a single
      ON attack (1). Among 23 NMO or RM patients seropositive for AQP4 autoantibodies
      by cell-based IIFA, comparison between those seropositive (n = 17) and
      seronegative (n = 6) by tissue-based IIFA revealed no differences in clinical and
      neuroradiological characteristics between the two groups. CONCLUSION: Cell-based
      IIFA is slightly more sensitive than tissue-based IIFA in detection of AQP4
      autoantibodies, which are highly specific for NMOSD.

PMID- 20822516
TI  - Acetylcholinesterase Inhibitors (AChEI's) for the treatment of visual
      hallucinations in schizophrenia: a case report.
AB  - BACKGROUND: Visual hallucinations are commonly seen in various neurological and
      psychiatric disorders including schizophrenia. Current models of visual
      processing and studies in diseases including Parkinsons Disease and Lewy Body
      Dementia propose that Acetylcholine (Ach) plays a pivotal role in our ability to
      accurately interpret visual stimuli. Depletion of Ach is thought to be associated
      with visual hallucination generation. AchEI's have been used in the targeted
      treatment of visual hallucinations in dementia and Parkinson's Disease patients.
      In Schizophrenia, it is thought that a similar Ach depletion leads to visual
      hallucinations and may provide a target for drug treatment CASE PRESENTATION: We
      present a case of a patient with Schizophrenia presenting with treatment
      resistant and significantly distressing visual hallucinations. After optimising
      treatment for schizophrenia we used Rivastigmine, an AchEI, as an adjunct to
      treat her symptoms successfully. CONCLUSIONS: This case is the first to
      illustrate this novel use of an AchEI in the targeted treatment of visual
      hallucinations in a patient with Schizophrenia. Targeted therapy of this kind can
      be considered in challenging cases although more evidence is required in this
      field.

PMID- 20822517
TI  - Acetylcholinesterase Inhibitors (AChEI's) for the treatment of visual
      hallucinations in schizophrenia: a review of the literature.
AB  - BACKGROUND: Visual hallucinations occur in various neurological diseases, but are
      most prominent in Lewy body dementia, Parkinson's disease and schizophrenia. The
      lifetime prevalence of visual hallucinations in patients with schizophrenia is
      much more common than conventionally thought and ranges from 24% to 72%. Cortical
      acetylcholine (ACh) depletion has been associated with visual hallucinations; the
      level of depletion being related directly to the severity of the symptoms.
      Current understanding of neurobiological visual processing and research in
      diseases with reduced cholinergic function, suggests that AChEI's may prove
      beneficial in treating visual hallucinations. This offers the potential for
      targeted drug therapy of clinically symptomatic visual hallucinations in patients
      with schizophrenia using acetylcholinesterase inhibition. METHODS: A systematic
      review was carried out investigating the evidence for the effects of AChEI's in
      treating visual hallucinations in Schizophrenia. RESULTS: No evidence was found
      relating to the specific role of AChEI's in treating visual hallucinations in
      this patient group. DISCUSSION: Given the use of AChEI's in targeted, symptom
      specific treatment in other neuropsychiatric disorders, it is surprising to find
      no related literature in schizophrenia patients. The use of AChEI's in
      schizophrenia has investigated effects on cognition primarily with non cognitive
      effects measured more broadly. CONCLUSIONS: We would suggest that more focused
      research into the effects of AChEI's on positive symptoms of schizophrenia,
      specifically visual hallucinations, is needed.

PMID- 20822518
TI  - Filtering, FDR and power.
AB  - BACKGROUND: In high-dimensional data analysis such as differential gene
      expression analysis, people often use filtering methods like fold-change or
      variance filters in an attempt to reduce the multiple testing penalty and improve
      power. However, filtering may introduce a bias on the multiple testing
      correction. The precise amount of bias depends on many quantities, such as
      fraction of probes filtered out, filter statistic and test statistic used.
      RESULTS: We show that a biased multiple testing correction results if non
      differentially expressed probes are not filtered out with equal probability from
      the entire range of p-values. We illustrate our results using both a simulation
      study and an experimental dataset, where the FDR is shown to be biased mostly by
      filters that are associated with the hypothesis being tested, such as the fold
      change. Filters that induce little bias on the FDR yield less additional power of
      detecting differentially expressed genes. Finally, we propose a statistical test
      that can be used in practice to determine whether any chosen filter introduces
      bias on the FDR estimate used, given a general experimental setup. CONCLUSIONS:
      Filtering out of probes must be used with care as it may bias the multiple
      testing correction. Researchers can use our test for FDR bias to guide their
      choice of filter and amount of filtering in practice.

PMID- 20822520
TI  - Grip strength measurements at two different wrist extension positions in chronic
      lateral epicondylitis-comparison of involved vs. uninvolved side in athletes and
      non athletes: a case-control study.
AB  - BACKGROUND: Lateral epicondylitis is a common sports injury of the elbow caused
      due to altered muscle activation during repetitive wrist extension in many
      athletic and non-athletic endeavours. The amount of muscle activity and timing of
      contraction eventually is directly dependent upon joint position during the
      activity. The purpose of our study was to compare the grip strength in athletes
      with lateral epicondylalgia in two different wrist extension positions and
      compare them between involved and uninvolved sides of athletes and non-athletes.
      METHODS: An assessor-blinded case-control study of eight athletes and twenty-two
      non-athletes was done. The grip strength was measured using JAMAR(r) hand
      dynamometer in kilograms-force at 15 degrees (slightly extended) and 35 degrees
      (moderately extended) wrist extension positions (maintained by wrist splints) on
      both involved and uninvolved sides of athletes and non-athletes with unilateral
      lateral epicondylitis of atleast 3 months duration. Their pain was to be elicited
      with local tenderness and two of three tests being positive- Cozen's, Mill's
      manoeuvre, resisted middle finger extension tests. For comparisons of grip
      strength, Wilcoxon signed rank test was used for within-group comparison (between
      15 and 35 degrees wrist extension positions) and Mann-Whitney U test was used for
      between-group (athletes vs. non-athletes) comparisons at 95% confidence interval
      and were done using SPSS 11.5 for Windows. RESULTS: Statistically significant
      greater grip strength was found in 15 degrees (27.75 +/- 4.2 kgms in athletes;
      16.45 +/- 4.2 kgms in non-athletes) wrist extension than at 35 degrees (25.25 +/-
      3.53 kgm in athletes and 14.18 +/- 3.53 kgm in non-athletes). The athletes had
      greater grip strength than non-athletes in each of test positions (11.3 kgm at 15
      degrees and 11.07 kgm at 35 degrees) measured. There was also a significant
      difference between involved and uninvolved sides' grip strength at both wrist
      positions (4.44 +/- .95 kgm at 15 degrees and 4.44 +/- .86 kgm in 35 degrees)
      which was significant (p < .05) only in non-athletes. CONCLUSION: The grip
      strength was greater in 15 degrees wrist extension position and this position
      could then be used in athletes with lateral epicondylalgia for grip strength
      assessment and designing wrist splint in this population.

PMID- 20822519
TI  - Associations of fetuin-A levels with vascular disease in type 2 diabetes patients
      with early diabetic nephropathy.
AB  - BACKGROUND: Ambigous results exist on fetuin-A as marker for vascular disease in
      type 2 diabetes. This study aims to define the role of fetuin-A as marker for
      micro- and macrovascular disease in a high risk population of patients with type
      2 diabetes mellitus and early diabetic nephropathy. METHODS: Fetuin-A serum
      levels were assessed by ELISA in a cross-sectional setting in 153 patients with
      type 2 diabetes. Associations of fetuin-A with metabolic, inflammatory and
      vascular markers were studied. Atherosclerotic burden was assessed by ankle
      brachial-index (ABI) as well as detection of common carotid artery intima-media
      thickness (IMT). RESULTS: Levels of fetuin-A were lower in male than in female
      patients (0.49 +/- 0.15 vs. 0.56 +/- 0.20 g/L, p = 0.02). In addition, there was
      an inverse correlation with age (r = -0.20, P = 0.01). Bivariate correlations
      adjusted for age and gender revealed no significant correlations with metabolic
      parameters, except for a weak inverse correlation with serum adiponectin (r = 
      0.19, p = 0.02). Regarding parameters of micro- and macrovascular disease, fetuin
      A was significantly associated with ABI (r = 0.18, p = 0.04), while there was no
      association with IMT (r = -0.07, p = n.s). Patients with an ABI < 0.9 had lower
      fetuin A levels than patients with an ABI 0.9-1.3 or > 1.3 (0.43 +/- 0.10 vs.
      0.52 +/- 0.17 vs. 0.54 +/- 0.18 g/L p = 0.05). Neither GFR nor albuminuria were
      associated with fetuin-A serum levels. Patients with prevalent neuropathy did not
      have altered fetuin-A levels compared to diabetic controls. In step-wise logistic
      regression analysis including age, gender, HbA1c, total cholesterol, glomerular
      filtration rate and fetuin-A, only total cholesterol (beta = 0.01, p = 0.02) and
      fetuin-A (beta = -5.99, p = 0.03) proved to be independent predictors of an ABI <
      0.9. CONCLUSIONS: The results of this cross-sectional study suggest that lower
      fetuin-A levels are associated with macrovascular late complications in high-risk
      type 2 diabetes patients while there are no associations of fetuin-A with
      metabolic status or microvascular complications.

PMID- 20822521
TI  - The perspectives of clients and unqualified allopathic practitioners on the
      management of delivery care in urban slums, Dhaka, Bangladesh - a mixed method
      study.
AB  - BACKGROUND: BRAC is implementing a program to improve maternal and newborn health
      among the urban poor in the slums of Bangladesh (Mansohi), funded by the Bill &
      Melinda Gates Foundation. Formative research has demonstrated that unqualified
      allopathic practitioners (UAPs) are commonly assisting home-delivery. The
      objective of this study was to explore the role of unqualified allopathic
      practitioners during home delivery in urban slums of Dhaka. METHODS: This cross
      sectional study was conducted between September 2008 and June 2009 in
      Kamrangirchar slum in Dhaka, Bangladesh, using both qualitative and quantitative
      research methods. Through a door-to-door household survey, quantitative data were
      collected from 463 women with a home birth and/or trial of labor at home. We also
      conducted seven in-depth interviews with the UAPs to explore their practices.
      RESULTS: About one-third (32%) of the 463 women interviewed sought delivery care
      from a UAP. We did not find an association between socio-demographic
      characteristics and care-seeking from a UAP, except for education of women.
      Compared to women with three or more pregnancies, the highest odds ratio was
      found in the primi-gravidity group [odds ratio (OR): 3.46; 95% confidence
      interval (CI): 1.65-7.25)], followed by women with two pregnancies (OR: 2.54; 95%
      CI: 1.36-4.77) to use a UAP. Of women who reported at least one delivery-related
      complication, 45.2% received care from the UAPs. Of 149 cases where the UAP was
      involved with delivery care, 133 (89.3%) received medicine to start or increase
      labor with only 6% (9 of 149) referred by a UAP to any health facility. The
      qualitative findings showed that UAPs provided a variety of medicines to manage
      excessive bleeding immediately after childbirth. CONCLUSION: There is demand
      among slum women for delivery-related care from UAPs during home births in
      Bangladesh. Some UAPs' practices are contrary to current World Health
      Organization recommendations and could be harmful. Programs need to develop
      interventions to address these practices to improve perinatal care outcomes.

PMID- 20822522
TI  - Association between HIV replication and serum leptin levels: an observational
      study of a cohort of HIV-1-infected South African women.
AB  - BACKGROUND: Advanced HIV infection can result in lipoatrophy and wasting, even in
      the absence of ongoing opportunistic infections, suggesting that HIV may directly
      affect adipose tissue amount and distribution. METHODS: We assessed the
      relationship of fat (measured using anthropometry, DEXA, MRI scans) or markers
      related to glucose and lipid metabolism with viral load in a cross-sectional
      sample of 83 antiretroviral-naive HIV-1-infected South African women. A
      multivariable linear model was fitted to log10VL to assess the combined effect of
      these variables. RESULTS: In addition to higher T cell activation, women with
      viral load greater than the population median had lower waist circumference, body
      mass index and subcutaneous abdominal fat, as well as lower serum leptin. We
      demonstrate that leptin serum levels are inversely associated with viral
      replication, independent of the amount of adipose tissue. This association is
      maintained after adjusting for multiple variables associated with disease
      progression (i.e., cellular activation and innate immunity effector levels).
      CONCLUSIONS: Our results demonstrate that serum leptin levels are inversely
      associated with viral replication, independent of disease progression: we
      postulate that leptin may affect viral replication.

PMID- 20822523
TI  - An ANOCEF genomic and transcriptomic microarray study of the response to
      radiotherapy or to alkylating first-line chemotherapy in glioblastoma patients.
AB  - BACKGROUND: The molecular characteristics associated with the response to
      treatment in glioblastomas (GBMs) remain largely unknown. We performed a
      retrospective study to assess the genomic characteristics associated with the
      response of GBMs to either first-line chemotherapy or radiation therapy. The gene
      expression (n = 56) and genomic profiles (n = 67) of responders and non
      responders to first-line chemotherapy or radiation therapy alone were compared on
      Affymetrix Plus 2 gene expression arrays and BAC CGH arrays. RESULTS: According
      to Verhaak et al.'s classification system, mesenchymal GBMs were more likely to
      respond to radiotherapy than to first-line chemotherapy, whereas classical GBMs
      were more likely to respond to first-line chemotherapy than to radiotherapy. In
      patients treated with radiation therapy alone, the response was associated with
      differential expression of microenvironment-associated genes; the expression of
      hypoxia-related genes was associated with short-term progression-free survival (<
      5 months), whereas the expression of immune genes was associated with prolonged
      progression-free survival (> 10 months). Consistently, infiltration of the tumor
      by both CD3 and CD68 cells was significantly more frequent in responders to
      radiotherapy than in non-responders. In patients treated with first-line
      chemotherapy, the expression of stem-cell genes was associated with resistance to
      chemotherapy, and there was a significant association between response to
      treatment and p16 locus deletions. Consistently, in an independent data set of
      patients treated with either radiotherapy alone or with both radiotherapy and
      adjuvant chemotherapy, we found that patients with the p16 deletion benefited
      from adjuvant chemotherapy regardless of their MGMT promoter methylation status,
      whereas in patients without the p16 deletion, this benefit was only observed in
      patients with a methylated MGMT promoter. CONCLUSION: Differential expression of
      microenvironment genes and p16 locus deletion are associated with responses to
      radiation therapy and to first-line chemotherapy, respectively, in GBM. Recently
      identified transcriptomic subgroups of GBMs seem to respond differently to
      radiotherapy and to first-line chemotherapy.

PMID- 20822524
TI  - Isoform of APOE with retained intron 3; quantitation and identification of an
      associated single nucleotide polymorphism.
AB  - BACKGROUND: Alleles of apolipoprotein E (APOE) are the major genetic risk factor
      for late onset Alzheimer's Disease (LOAD). Recently, an APOE splice variant that
      retains intron 3 (APOE-I3) was identified. To gain insight into the possible role
      of this isoform in LOAD, we quantified its expression in a cohort of 56 human
      brain specimens by using quantitative RT-PCR. RESULTS: We found that APOE-I3
      generally represents a low percentage (< 0.5%) of overall APOE expression.
      However, in one specimen, the proportion of APOE-I3 was increased about ~13 fold.
      This specimen was unique in the cohort for possessing the minor allele of an
      intron 3 single nucleotide polymorphism (SNP), rs12982192. Additionally, an
      allelic expression imbalance study indicated that the rs12982192 minor allele was
      associated with increased APOE-I3 expression. CONCLUSIONS: Overall, we interpret
      our results as suggesting that APOE-I3 represents a minor portion of APOE
      expression and that rs12982192 is associated with APOE intron 3 retention. Since
      the minor allele of this SNP is on the same haplotype as the minor allele of
      rs429358, which defines the APOE4 allele, we speculate that rs12982192 may
      reflect a modest loss of mRNA encoding functional APOE4.

PMID- 20822525
TI  - Tumor interactions with soluble factors and the nervous system.
AB  - In the genomic era of cancer research, the development of metastases has been
      attributed to mutations in the tumor that enable the cells to migrate. However,
      gene analyses revealed that primary tumors and metastases were in some cases
      genetically identical and the question was raised whether metastasis formation
      might be an inherent feature of certain tumor cells. In contradiction to this
      view, the last decade of cancer research has brought to light, that tumor cell
      migration, similar to leukocyte and fibroblast migration, is a highly regulated
      process. The nervous system plays an important role in this regulation, at least
      in two respects: firstly, neurotransmitters are known to regulate the migratory
      activity of tumor cells, and secondly, nerve fibers are used as routes for
      perineural invasion. We also summarize here the current knowledge on the
      innervation of tumors. Such a process might establish a neuro-neoplastic synapse,
      with the close interaction of tumor cells and nerve cells supporting metastasis
      formation.

PMID- 20822526
TI  - The role of the tissue microenvironment in the regulation of cancer cell motility
      and invasion.
AB  - During malignant neoplastic progression the cells undergo genetic and epigenetic
      cancer-specific alterations that finally lead to a loss of tissue homeostasis and
      restructuring of the microenvironment. The invasion of cancer cells through
      connective tissue is a crucial prerequisite for metastasis formation. Although
      cell invasion is foremost a mechanical process, cancer research has focused
      largely on gene regulation and signaling that underlie uncontrolled cell growth.
      More recently, the genes and signals involved in the invasion and
      transendothelial migration of cancer cells, such as the role of adhesion
      molecules and matrix degrading enzymes, have become the focus of research. In
      this review we discuss how the structural and biomechanical properties of
      extracellular matrix and surrounding cells such as endothelial cells influence
      cancer cell motility and invasion. We conclude that the microenvironment is a
      critical determinant of the migration strategy and the efficiency of cancer cell
      invasion.

PMID- 20822527
TI  - Analysis of Ggamma-158(C->T) polymorphism in hemoglobin E/beta-thalassemia major
      in Southern China.
AB  - BACKGROUND: The Ggamma-158(C->T) polymorphism plays important function in the
      clinical variability of HbE/beta-thalassemia. There is little known about Ggamma
      158(C->T) polymorphism in HbE/beta-thalassemia major in Southern China. This
      study aimed to explore the association between HbE/beta-thalassemia major and
      this polymorphism in Southern China. METHODS AND RESULTS: The frequency of the
      Ggamma-158(C->T) polymorphism has been evaluated in 32 patients with HbE/beta
      thalassemia major from Southern China. Further analysis of the Ggamma-158(C->T)
      polymorphism revealed the prominent frequency of this polymorphic pattern among
      HbE/beta-thalassemia major patients (65.63%). The presence of this polymorphism
      was strongly correlated with the increase of HbF synthesis. CONCLUSIONS: The
      frequency of the Ggamma-158(C->T) polymorphism was relatively high in Southern
      Chinese patients with HbE/beta-thalassemia major, often accompanying with high
      production of HbF. This feature appears to be different with reports in other
      races and regions.

PMID- 20822528
TI  - Rac and Rho GTPases in cancer cell motility control.
AB  - Rho GTPases represent a family of small GTP-binding proteins involved in cell
      cytoskeleton organization, migration, transcription, and proliferation. A common
      theme of these processes is a dynamic reorganization of actin cytoskeleton which
      has now emerged as a major switch control mainly carried out by Rho and Rac
      GTPase subfamilies, playing an acknowledged role in adaptation of cell motility
      to the microenvironment. Cells exhibit three distinct modes of migration when
      invading the 3 D environment. Collective motility leads to movement of cohorts of
      cells which maintain the adherens junctions and move by photolytic degradation of
      matrix barriers. Single cell mesenchymal-type movement is characterized by an
      elongated cellular shape and again requires extracellular proteolysis and
      integrin engagement. In addition it depends on Rac1-mediated cell polarization
      and lamellipodia formation. Conversely, in amoeboid movement cells have a rounded
      morphology, the movement is independent from proteases but requires high Rho
      GTPase to drive elevated levels of actomyosin contractility. These two modes of
      cell movement are interconvertible and several moving cells, including tumor
      cells, show an high degree of plasticity in motility styles shifting ad hoc
      between mesenchymal or amoeboid movements. This review will focus on the role of
      Rac and Rho small GTPases in cell motility and in the complex relationship
      driving the reciprocal control between Rac and Rho granting for the opportunistic
      motile behaviour of aggressive cancer cells. In addition we analyse the role of
      these GTPases in cancer progression and metastatic dissemination.

PMID- 20822529
TI  - Hemin inhibits NO production by IL-1beta-stimulated human astrocytes through
      induction of heme oxygenase-1 and reduction of p38 MAPK activation.
AB  - BACKGROUND: Heme oxygenase (HO)-1 has been shown to attenuate oxidative injury
      and reduce apoptosis. HO-1 can be induced by various stimuli released during
      cellular injury, such as heme. Deleterious free heme is degraded by HO-1 to
      carbon monoxide, iron and biliverdin, which have potent anti-oxidant and anti
      inflammatory properties. In this study, we tested the hypothesis that
      upregulation of HO-1 would inhibit production of the free radical (NO) by
      interleukin (IL)-1beta-activated human astrocytes. METHODS: To measure NO
      production, inducible NO synthase (iNOS), HO-1 expression and mitogen-activated
      protein (MAP) kinase activation we used hemin as an HO-1 inducer and tin
      protoporphyrin (SnPP) IX as an inhibitor of HO-1 activity in human astrocyte
      cultures prior to IL-1beta exposure. Transfection of astrocyte cultures was
      performed using a pLEX expression vector carrying the human HO-1 sequence prior
      to IL-1beta treatment. Supernatants of astrocyte cultures pretreated with
      inhibitors of p38 MAPK or MEK1/2 prior to IL-1beta exposure were collected for NO
      assay. RESULTS: IL-1beta treatment of astrocytes alone induced undetectable
      amounts of HO-1 protein by western blot. However, HO-1 mRNA expression was
      modestly up-regulated in response to IL-1beta stimulation. Pretreatment with
      hemin alone substantially induced both HO-1 mRNA and protein expression, and HO-1
      mRNA expression was further enhanced when hemin was combined with IL-1beta
      treatment. In contrast, IL-1beta-induced iNOS mRNA expression and NO production
      were markedly inhibited by hemin treatment. When pretreated with SnPP, the
      inhibitory effect of hemin on IL-1beta-induced NO production and iNOS expression
      was reversed, suggesting the involvement of HO-1. IL-1beta-induced p38 MAPK
      activation, which is known to be required for NO production, was also down
      regulated by hemin. CONCLUSION: These findings support the hypothesis that up
      regulation of HO-1 in astrocytes is associated with down-regulation of iNOS
      expression and thereby NO production, an effect that involves the p38 MAPK
      signaling pathway, which suggests that this glial cell response could play an
      important protective role against oxidative stress in the brain.

PMID- 20822530
TI  - Standardized ultrasound evaluation of carotid stenosis for clinical trials:
      University of Washington Ultrasound Reading Center.
AB  - INTRODUCTION: Serial monitoring of patients participating in clinical trials of
      carotid artery therapy requires noninvasive precision methods that are
      inexpensive, safe and widely available. Noninvasive ultrasonic duplex Doppler
      velocimetry provides a precision method that can be used for recruitment
      qualification, pre-treatment classification and post treatment surveillance for
      remodeling and restenosis. The University of Washington Ultrasound Reading Center
      (UWURC) provides a uniform examination protocol and interpretation of duplex
      Doppler velocity measurements. METHODS: Doppler waveforms from 6 locations along
      the common carotid and internal carotid artery path to the brain plus the
      external carotid and vertebral arteries on each side using a Doppler examination
      angle of 60 degrees are evaluated. The UWURC verifies all measurements against
      the images and waveforms for the database, which includes pre-procedure, post
      procedure and annual follow-up examinations. Doppler angle alignment errors
      greater than 3 degrees and Doppler velocity measurement errors greater than 0.05
      m/s are corrected. RESULTS: Angle adjusted Doppler velocity measurements produce
      higher values when higher Doppler examination angles are used. The definition of
      peak systolic velocity varies between examiners when spectral broadening due to
      turbulence is present. Examples of measurements are shown. DISCUSSION: Although
      ultrasonic duplex Doppler methods are widely used in carotid artery diagnosis,
      there is disagreement about how the examinations should be performed and how the
      results should be validated. In clinical trails, a centralized reading center can
      unify the methods. Because the goals of research examinations are different from
      those of clinical examinations, screening and diagnostic clinical examinations
      may require fewer velocity measurements.

PMID- 20822531
TI  - VIGOR, an annotation program for small viral genomes.
AB  - BACKGROUND: the decrease in cost for sequencing and improvement in technologies
      has made it easier and more common for the re-sequencing of large genomes as well
      as parallel sequencing of small genomes. It is possible to completely sequence a
      small genome within days and this increases the number of publicly available
      genomes. Among the types of genomes being rapidly sequenced are those of
      microbial and viral genomes responsible for infectious diseases. However,
      accurate gene prediction is a challenge that persists for decoding a newly
      sequenced genome. Therefore, accurate and efficient gene prediction programs are
      highly desired for rapid and cost effective surveillance of RNA viruses through
      full genome sequencing. RESULTS: we have developed VIGOR (Viral Genome ORF
      Reader), a web application tool for gene prediction in influenza virus,
      rotavirus, rhinovirus and coronavirus subtypes. VIGOR detects protein coding
      regions based on sequence similarity searches and can accurately detect genome
      specific features such as frame shifts, overlapping genes, embedded genes, and
      can predict mature peptides within the context of a single polypeptide open
      reading frame. Genotyping capability for influenza and rotavirus is built into
      the program. We compared VIGOR to previously described gene prediction programs,
      ZCURVE_V, GeneMarkS and FLAN. The specificity and sensitivity of VIGOR are
      greater than 99% for the RNA viral genomes tested. CONCLUSIONS: VIGOR is a user
      friendly web-based genome annotation program for five different viral agents,
      influenza, rotavirus, rhinovirus, coronavirus and SARS coronavirus. This is the
      first gene prediction program for rotavirus and rhinovirus for public access.
      VIGOR is able to accurately predict protein coding genes for the above five viral
      types and has the capability to assign function to the predicted open reading
      frames and genotype influenza virus. The prediction software was designed for
      performing high throughput annotation and closure validation in a post-sequencing
      production pipeline.

PMID- 20822532
TI  - An automated in vitro model for the evaluation of ultrasound modalities measuring
      myocardial deformation.
AB  - BACKGROUND: Echocardiography is the method of choice when one wishes to examine
      myocardial function. Qualitative assessment of the 2D grey scale images obtained
      is subjective, and objective methods are required. Speckle Tracking Ultrasound is
      an emerging technology, offering an objective mean of quantifying left
      ventricular wall motion. However, before a new ultrasound technology can be
      adopted in the clinic, accuracy and reproducibility needs to be investigated.
      AIM: It was hypothesized that the collection of ultrasound sample data from an in
      vitro model could be automated. The aim was to optimize an in vitro model to
      allow for efficient collection of sample data. MATERIAL & METHODS: A tissue
      mimicking phantom was made from water, gelatin powder, psyllium fibers and a
      preservative. Sonomicrometry crystals were molded into the phantom. The solid
      phantom was mounted in a stable stand and cyclically compressed. Peak strain was
      then measured by Speckle Tracking Ultrasound and sonomicrometry. RESULTS: We
      succeeded in automating the acquisition and analysis of sample data. Sample data
      was collected at a rate of 200 measurement pairs in 30 minutes. We found good
      agreement between Speckle Tracking Ultrasound and sonomicrometry in the in vitro
      model. Best agreement was 0.83 +/- 0.70%. Worst agreement was -1.13 +/- 6.46%.
      CONCLUSIONS: It has been shown possible to automate a model that can be used for
      evaluating the in vitro accuracy and precision of ultrasound modalities measuring
      deformation. Sonomicrometry and Speckle Tracking Ultrasound had acceptable
      agreement.

PMID- 20822533
TI  - Environmental control of invasiveness and metastatic dissemination of tumor
      cells: the role of tumor cell-host cell interactions.
AB  - Recent advances in tumor biology led to the realization that, in order to
      understand the mechanisms involved in proliferation and invasion of tumor cells,
      an analysis of the complex interactions that tumor cells establish with host
      cells of tumor microenvironment is required. The bidirectional interactions
      between tumor cells and components of tumor microenvironment, in particular
      endothelial cells, cells of monocyte/macrophage lineage and
      fibroblasts/myofibroblasts, play a critical role in most of the events that
      characterize tumor progression and metastasis. Interactions between these
      "reactive" normal cells and the genetically altered tumor cells, by either cell
      to-cell contacts or soluble mediators, control the most aspects of tumor
      formation and progression. This review addresses some of the experimental
      evidences documenting that tumor cells may influence host cells of their own
      microenvironment by triggering changes that facilitate their local as well as
      distant dissemination. Therefore, it focuses on macrophages and fibroblasts that,
      upon stimulation by tumor cells, change their state towards a tumor-promoting
      like phenotype.

PMID- 20822534
TI  - Escaping from, moving towards, following a path, squeezing through: lots of
      opportunities for moving cells.

PMID- 20822536
TI  - Large-scale data integration framework provides a comprehensive view on
      glioblastoma multiforme.
AB  - BACKGROUND: Coordinated efforts to collect large-scale data sets provide a basis
      for systems level understanding of complex diseases. In order to translate these
      fragmented and heterogeneous data sets into knowledge and medical benefits,
      advanced computational methods for data analysis, integration and visualization
      are needed. METHODS: We introduce a novel data integration framework, Anduril,
      for translating fragmented large-scale data into testable predictions. The
      Anduril framework allows rapid integration of heterogeneous data with state-of
      the-art computational methods and existing knowledge in bio-databases. Anduril
      automatically generates thorough summary reports and a website that shows the
      most relevant features of each gene at a glance, allows sorting of data based on
      different parameters, and provides direct links to more detailed data on genes,
      transcripts or genomic regions. Anduril is open-source; all methods and
      documentation are freely available. RESULTS: We have integrated multidimensional
      molecular and clinical data from 338 subjects having glioblastoma multiforme, one
      of the deadliest and most poorly understood cancers, using Anduril. The central
      objective of our approach is to identify genetic loci and genes that have
      significant survival effect. Our results suggest several novel genetic
      alterations linked to glioblastoma multiforme progression and, more specifically,
      reveal Moesin as a novel glioblastoma multiforme-associated gene that has a
      strong survival effect and whose depletion in vitro significantly inhibited cell
      proliferation. All analysis results are available as a comprehensive website.
      CONCLUSIONS: Our results demonstrate that integrated analysis and visualization
      of multidimensional and heterogeneous data by Anduril enables drawing conclusions
      on functional consequences of large-scale molecular data. Many of the identified
      genetic loci and genes having significant survival effect have not been reported
      earlier in the context of glioblastoma multiforme. Thus, in addition to generally
      applicable novel methodology, our results provide several glioblastoma multiforme
      candidate genes for further studies.Anduril is available at
      http://csbi.ltdk.helsinki.fi/anduril/The glioblastoma multiforme analysis results
      are available at http://csbi.ltdk.helsinki.fi/anduril/tcga-gbm/

PMID- 20822535
TI  - Non-dominant hand movement facilitates the frontal N30 somatosensory evoked
      potential.
AB  - BACKGROUND: Previous literature has shown that the frontal N30 is increased
      during movement of the hand contralateral to median nerve stimulation. This
      finding was a result of non-dominant left hand movement in right-handed
      participants. It is unclear however if the effect depends upon non-dominant hand
      movement or if this is a generalized phenomenon across the upper-limbs. This
      study tests the effect of dominant and non-dominant hand movement upon
      contralateral frontal and parietal somatosensory evoked potentials (SEPs) and
      further tests if this relationship persists in left hand dominant participants.
      Median nerve SEPs were elicited from the wrist contralateral to movement in both
      right hand and left hand dominant participants alternating the movement hand in
      separate blocks. Participants were required to volitionally squeeze (~20% of a
      maximal voluntary contraction) a pressure-sensitive bulb every ~3 seconds with
      the hand contralateral to median nerve stimulation. SEPs were continuously
      collected during the task and individual traces were grouped into time bins
      relative to movement according to the timing of components of the
      Bereitschaftspotential. SEPs were then averaged and quantified from both FCZ and
      CP3/4 scalp electrode sites during both the squeeze task and at rest. RESULTS:
      The N30 is facilitated during non-dominant hand movement in both right and left
      hand dominant individuals. There was no effect for dominant hand movement in
      either group. CONCLUSIONS: N30 amplitude increase may be a result of altered
      sensory gating from motor areas known to be specifically active during non
      dominant hand movement.

PMID- 20822537
TI  - Antibiotic-free selection in E. coli: new considerations for optimal design and
      improved production.
AB  - BACKGROUND: The increasing regulatory requirements to which biological agents are
      subjected will have a great impact in the field of industrial protein expression
      and production. There is an expectation that in a near future, there may be "zero
      tolerance" towards antibiotic-based selection and production systems. Besides the
      antibiotic itself, the antibiotic resistance gene is an important consideration.
      The complete absence of antibiotic-resistance gene being the only way to ensure
      that there is no propagation in the environment or transfer of resistance to
      pathogenic strains. RESULTS: In a first step, we have designed a series of
      vectors, containing a stabilization element allowing a complete elimination of
      antibiotics during fermentation. Vectors were further improved in order to
      include alternative selection means such as the well known poison/antidote
      stabilization system. Eventually we propose an elegant positive pressure of
      selection ensuring the elimination of the antibiotic-resistance gene through
      homologous recombination. In addition, we have shown that the presence of an
      antibiotic resistance gene can indirectly reduce the amount of expressed protein,
      since even in absence of selection pressure the gene would be transcribed and
      account for an additional stress for the host during the fermentation process.
      CONCLUSIONS: We propose a general strategy combining plasmid stabilization and
      antibiotic-free selection. The proposed host/vector system, completely devoid of
      antibiotic resistance gene at the end of construction, has the additional
      advantage of improving recombinant protein expression and/or plasmid recovery.

PMID- 20822538
TI  - A six-generation Chinese family in haplogroup B4C1C exhibits high penetrance of
      1555A > G-induced hearing Loss.
AB  - BACKGROUND: The 1555A > G mutation is the most common cause of aminoglycoside
      induced and non-syndromic deafness. However, the variable clinical phenotype and
      incomplete penetrance of A1555G-induced hearing loss complicate our understanding
      of this mutation. Environmental factors, nuclear genes, mitochondrial
      haplotypes/variants and a possible threshold effect have been reported to may be
      involved in its manifestation. METHODS: Here, we performed a clinical, molecular,
      genetic and phylogenic analysis in a six-generation Chinese family. RESULTS: A
      clinical evaluation revealed that affected individuals without aminoglycoside
      exposure developed hearing loss extending gradually from 12000 Hz to 8000 Hz and
      then to 4000 Hz. Using pyrosequencing, we detected an identical homoplasmic 1555A
      > G mutation in all individuals except one. We did not find any correlation
      between the mutation load and the severity of hearing loss. T123N coexisted with
      the 1555A > G mutation in six affected subjects in our pedigree. Analysis of the
      complete mtDNA genome of this family revealed that this family belonged to
      haplotype B4C1C and exhibited high penetrance. Upon the inclusion of subjects
      that had been exposed to aminoglycosides, the penetrance of the hearing loss was
      63.6%.; without exposure to aminoglycosides, it was 51.5%. This pedigree and
      another reported Chinese pedigree share the same haplotype (B4C1C) and lack
      functionally significant mitochondrial tRNA variants, but nevertheless they
      exhibit a different penetrance of hearing loss. CONCLUSIONS: Our results imply
      that the factors responsible for the higher penetrance and variable expression of
      the deafness associated with the 1555A > G mutation in this pedigree may not be
      mtDNA haplotype/variants, but rather nuclear genes and/or aminoglycosides.

PMID- 20822539
TI  - Bleeding disorders in the tribe: result of consanguineous in breeding.
AB  - OBJECTIVE: To determine the frequency and clinical features of bleeding disorders
      in the tribe as a result of consanguineous marriages. DESIGN: Cross Sectional
      Study INTRODUCTION: Countries in which consanguinity is a normal practice, these
      rare autosomal recessive disorders run in close families and tribes. Here we
      describe a family, living in village Ali Murad Chandio, District Badin, labeled
      as haemophilia. PATIENTS & METHODS: Our team visited the village & developed the
      pedigree of the whole extended family, up to seven generations. Performa was
      filled by incorporating patients, family history of bleeding, signs & symptoms,
      and bleeding from any site. From them 144 individuals were screened with CBC,
      bleeding time, platelet aggregation studies & RiCoF. While for PT, APTT, VWF
      assay and Factor VIII assay, samples were kept frozen at -70 degrees C until
      tested. RESULTS: The family tree of the seven generations comprises of 533
      individuals, 63 subjects died over a period of 20 years and 470 were alive. Out
      of all those 144 subjects were selected on the basis of the bleeding history.
      Among them 98(68.1%) were diagnosed to have a bleeding disorder; 44.9% patients
      were male and 55.1% patients were female. Median age of all the patients was
      20.81, range (4 months- 80 yrs). The results of bleeding have shown that majority
      had gum bleeding, epistaxis and menorrhagia. Most common bleeding disorder was
      Von Willebrand disease and Platelet functional disorders. CONCLUSION:
      Consanguineous marriages keep all the beneficial and adversely affecting
      recessive genes within the family; in homozygous states. These genes express
      themselves and result in life threatening diseases. Awareness, education &
      genetic counseling will be needed to prevent the spread of such common occurrence
      of these bleeding disorders in the community.

PMID- 20822540
TI  - Effect of cAMP derivates on assembly and maintenance of tight junctions in human
      umbilical vein endothelial cells.
AB  - BACKGROUND: Endothelial tight and adherens junctions control a variety of
      physiological processes like adhesion, paracellular transport of solutes or
      trafficking of activated leukocytes. Formation and maintenance of endothelial
      junctions largely depend on the microenvironment of the specific vascular bed and
      on interactions of the endothelium with adjacent cell types. Consequently,
      primary cultures of endothelial cells often lose their specific junctional
      pattern and fail to establish tight monolayer in vitro. This is also true for
      endothelial cells isolated from the vein of human umbilical cords (HUVEC) which
      are widely used as model for endothelial cell-related studies. RESULTS: We here
      compared the effect of cyclic 3'-5'-adenosine monophosphate (cAMP) and its
      derivates on formation and stabilization of tight junctions and on alterations in
      paracellular permeability in HUVEC. We demonstrated by light and confocal laser
      microscopy that for shorter time periods the sodium salt of 8-bromoadenosine-cAMP
      (8-Br-cAMP/Na) and for longer incubation periods 8-(4-chlorophenylthio)-cAMP
      (pCPT-cAMP) exerted the greatest effects of all compounds tested here on
      formation of continuous tight junction strands in HUVEC. We further demonstrated
      that although all compounds induced protein kinase A-dependent expression of the
      tight junction proteins claudin-5 and occludin only pCPT-cAMP slightly enhanced
      paracellular barrier functions. Moreover, we showed that pCPT-cAMP and 8-Br
      cAMP/Na induced expression and membrane translocation of tricellulin.
      CONCLUSIONS: pCPT-cAMP and, to a lesser extend, 8-Br-cAMP/Na improved formation
      of continuous tight junction strands and decreased paracellular permeability in
      primary HUVEC. We concluded that under these conditions HUVEC represent a
      feasible in vitro model to study formation and disassembly of endothelial tight
      junctions and to characterize tight junction-associated proteins.

PMID- 20822541
TI  - Inhibition of class II histone deacetylases in the spinal cord attenuates
      inflammatory hyperalgesia.
AB  - BACKGROUND: Several classes of histone deacetylases (HDACs) are expressed in the
      spinal cord that is a critical structure of the nociceptive pathway. HDAC
      regulated histone acetylation is an important component of chromatin remodeling
      leading to epigenetic regulation of gene transcription. To understand the role of
      histone acetylation in epigenetic regulation of pathological pain, we have
      studied the impact of different classes of HDACs in the spinal cord on
      inflammatory hyperalgesia induced by complete Freund's adjuvant (CFA). RESULTS:
      We intrathecally applied inhibitors specific to different classes of HDACs and
      evaluated their impact on inflammatory hyperalgesia. Pre-injected inhibitors
      targeting class I as well as II (SAHA, TSA, LAQ824) or IIa (VPA, 4-PB) HDACs
      significantly delayed the thermal hyperalgesia induced by unilateral CFA
      injection in the hindpaw. Existing hyperalgesia induced by CFA was also
      attenuated by the HDAC inhibitors (HDACIs). In contrast, these inhibitors did not
      interfere with the thermal response either in naive animals, or on the
      contralateral side of inflamed animals. Interestingly, MS-275 that specifically
      inhibits class I HDACs failed to alter the hyperalgesia although it increased
      histone 3 acetylation in the spinal cord as SAHA did. Using immunoblot analysis,
      we further found that the levels of class IIa HDAC members (HDAC4, 5, 7, 9) in
      the spinal dorsal horn were upregulated following CFA injection while those of
      class I HDAC members (HDAC1, 2, 3) remained stable or were slightly reduced.
      CONCLUSIONS: Our data suggest that activity of class II HDACs in the spinal cord
      is critical to the induction and maintenance of inflammatory hyperalgesia induced
      by CFA, while activity of class I HDACs may be unnecessary. Comparison of the
      effects of HDACIs specific to class II and IIa as well as the expression pattern
      of different HDACs in the spinal cord in response to CFA suggests that the
      members of class IIa HDACs may be potential targets for attenuating persistent
      inflammatory pain.

PMID- 20822542
TI  - The effect of infliximab plus methotrexate on the modulation of inflammatory
      disease markers in juvenile idiopathic arthritis: analyses from a randomized,
      placebo-controlled trial.
AB  - BACKGROUND: We evaluated the effect of infliximab on markers of inflammation in
      patients with juvenile idiopathic arthritis (JIA). METHODS: In this randomized,
      placebo-controlled substudy, 122 patients with JIA received infliximab 3 mg/kg +
      methotrexate (MTX)(n = 60) or placebo + MTX (n = 62) at weeks 0, 2, and 6. At
      week 14, patients receiving placebo + MTX crossed over to infliximab 6 mg/kg +
      MTX; patients receiving infliximab 3 mg/kg + MTX continued treatment through week
      44. Sera and plasma from eligible patients receiving infliximab 3 mg/kg + MTX (n
      = 34) and receiving placebo->infliximab 6 mg/kg +MTX (n = 38) were collected at
      weeks 0, 2, 14, 16, 28, and 52 and analyzed for inflammatory markers (IL-6, IL
      12p40, ICAM-1, MMP-3, VEGF, TNF-alpha, and CRP). RESULTS: At week 2, decreases
      from baseline in IL-6, ICAM-1, MMP-3, TNF-alpha, and CRP were greater with
      infliximab versus placebo treatment, and with the exception of CRP, these
      differences were generally maintained through week 14. The decreases from
      baseline to week 52 in IL-6, ICAM-1, VEGF, MMP-3, and CRP and increases in IL
      12p40 levels were larger in patients receiving placebo->infliximab 6 mg/kg +MTX
      versus infliximab 3 mg/kg + MTX treatment. Patients receiving infliximab 3
      mg/kg+MTX who achieved an American College of Rheumatology Pediatric 30 (ACR-Pedi
      30) response had significantly larger decreases from baseline in ICAM-1 (p =
      0.0105) and MMP-3 (p = 0.0253) at week 2 and in ICAM-1 (p = 0.0304), MMP-3 (p =
      0.0091), and CRP (p = 0.0011) at week 14 versus ACR-Pedi-30 nonresponders.
      CONCLUSION: Infliximab + MTX attenuated several inflammatory markers in patients
      with JIA; larger decreases in ICAM-1, MMP-3, and CRP levels were observed in ACR
      Pedi-30 responders versus nonresponders. TRIAL REGISTRATION: NCT00036374.

PMID- 20822543
TI  - A cluster randomised trial to evaluate a physical activity intervention among 3-5
      year old children attending long day care services: study protocol.
AB  - BACKGROUND: Young children are not participating in recommended levels of
      physical activity and exhibit high levels of sedentary behaviour. Childcare
      services provide access to large numbers of young children for prolonged periods,
      yet there is limited experimental evidence regarding the effectiveness of
      physical activity interventions implemented in this setting. The aim of this
      study is to assess the effectiveness and acceptability of a multi-component
      physical activity intervention, delivered by childcare service staff, in
      increasing the physical activity levels of children attending long day care
      services. METHODS/DESIGN: The study will employ a cluster randomised controlled
      trial design. Three hundred children aged between 3-5 years from twenty randomly
      selected long day care services in the Hunter Region of New South Wales,
      Australia will be invited to participate in the trial. Ten of the 20 long day
      care services will be randomly allocated to deliver the intervention with the
      remaining ten services allocated to a wait list control group. The physical
      activity intervention will consist of a number of strategies including:
      delivering structured fundamental movement skill activities, increasing physical
      activity opportunities, increasing staff role modelling, providing children with
      a physical activity promoting indoor and outdoor environment and limiting
      children's small screen recreation and sedentary behaviours. Intervention
      effectiveness will be measured via child physical activity levels during
      attendance at long day care. The study also seeks to determine the acceptability
      and extent of implementation of the intervention by services and their staff
      participating in the study. DISCUSSION: The trial will address current gaps in
      the research evidence base and contribute to the design and delivery of future
      interventions promoting physical activity for young children in long day care
      settings. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
      ACTRN12610000087055.

PMID- 20822544
TI  - Comparing the probability of stroke by the Framingham risk score in hypertensive
      Korean patients visiting private clinics and tertiary hospitals.
AB  - BACKGROUND: The purpose of this study was to investigate the pattern of
      distribution of risk factors for stroke and the 10-year probability of stroke by
      the Framingham risk score in hypertensive patients visiting private clinics vs.
      tertiary hospitals. METHODS: A total of 2,490 hypertensive patients who attended
      61 private clinics (1088 patients) and 37 tertiary hospitals (1402 patients) were
      enrolled. The risk factors for stroke were evaluated using a series of laboratory
      tests and physical examinations, and the 10-year probability of stroke was
      determined by applying the Framingham stroke risk equation. RESULTS: The
      proportion of patients who had uncontrolled hypertension despite the use of
      antihypertensive agents was 49% (66 and 36% of patients cared for at private
      clinics and tertiary hospitals, respectively; p < 0.001). The average 10-year
      probability of stroke by the Framingham risk score in hypertensive patients was
      21% (approximately 2.2 times higher than of the risk of stroke in the Korean
      Cancer Prevention Study [KCPS] cohort) and was higher in patients attending
      tertiary hospitals compared to private clinics (16 and 24% of patients attending
      private clinics and tertiary hospitals, respectively; p < 0.001). CONCLUSIONS:
      Since the 10-year probability of stroke by the Framingham risk score in
      hypertensive patients attending tertiary hospitals was higher than the risk for
      patients attending private clinics. We suggest that the more aggressive
      interventions are needed to prevent and early detect an attack of stroke in
      hypertensive patients attending tertiary hospitals.

PMID- 20822545
TI  - Comparative analysis of proteome maps of silkworm hemolymph during different
      developmental stages.
AB  - BACKGROUND: The silkworm Bombyx mori is a lepidopteran insect with four
      developmental stages: egg, larva (caterpillar), pupa, and adult. The hemolymph of
      the silkworm is in an open system that circulates among all organs, and functions
      in nutrient and hormone transport, injury, and immunity. To understand the
      intricate developmental mechanisms of metamorphosis, silkworm hemolymph from
      different developmental stages, including the 3rd day of fifth instar, the 6th
      day of fifth instar, the 3rd day of pupation, the 8th day of pupal stage and the
      first day of the moth stage, was investigated by two-dimensional electrophoresis
      and mass spectrometry. RESULTS: Two-dimensional polyacrylamide gel
      electrophoresis showed that from the larval to moth stages, silkworm hemolymph
      proteins changed markedly. Not only did major proteins such as SP1, SP2, and the
      30 K lipoprotein change, but other proteins varied greatly at different stages.
      To understand the functions of these proteins in silkworm development, 56 spots
      were excised from gels for analysis by matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry (MALDI-TOF MS). We identified 34
      proteins involved in metamorphosis, programmed cell death, food digestion,
      metabolism, and nutrient storage and transport. Most proteins showed different
      expression at different stages, suggesting functions in development and
      metamorphosis. An abundance of proteins related to immunity were found, including
      hemolin, prophenoloxidase, serine proteinase-like protein, paralytic peptide
      binding protein, and protease inhibitor. CONCLUSIONS: Proteomics research not
      only provides the opportunity for direct investigation of protein expression
      patterns, but also identifies many attractive candidates for further study. Two
      dimensional maps of hemolymph proteins expressed during the growth and
      metamorphosis of the silkworm offer important insights into hemolymph function
      and insect metamorphosis.

PMID- 20822546
TI  - Improving responses to depression and related disorders: evaluation of a
      innovative, general, mental health care workers training program.
AB  - BACKGROUND: Australian General Practitioners have been beneficiaries of extensive
      training in mental health care delivery over the last few years but less so other
      workers who support those with mental illness. Training is needed as it is widely
      recognised that the most effective interventions to prevent and treat mental
      disorders are often not readily available. The Mental Health Aptitudes into
      Practice (MAP) training package is a broad, innovative, interdisciplinary,
      general mental health training aimed at improving responses to individuals with
      depression and related disorders. The modular structure of this training program
      meant that such training could be targeted at those with varied backgrounds. Two
      hundred and seventy one days of free MAP training was delivered across Victoria
      in 2004/2005. The evaluation reported here assessed whether changes occurred in
      the trainees' confidence, mental health literacy, attitudes towards effective
      treatments, mental health knowledge and skills and community mental health
      ideology following training. METHODS: These elements were assessed using pen and
      paper tests prior, immediately following, 6 months after and then 12 months after
      the training. Trainees' confidence, mental health literacy and social distance
      were measured using scales that have been used in evaluations of Mental Health
      First Aid Training. Community mental health ideology was measured using a sub
      scale of the Community Attitudes to the Mentally Ill (CAMI) scale. The trainees'
      knowledge and skills were accessed using instrumentation specifically designed
      for this evaluation. RESULTS: Following training, participants had more
      confidence in their ability to work with those who have mental health issues and
      less desire for social distance from them. Participants' knowledge and skills in
      relation to the treatment of mental disorders increased. These changes were
      observed immediately after training. The limited existing evidence suggests these
      changes were sustained six and twelve months later. CONCLUSIONS: MAP training can
      be used to develop the capacity and capabilities of mental health workers.

PMID- 20822547
TI  - Alternative way to test the efficacy of swine FMD vaccines: measurement of pigs
      median infected dose (PID50) and regulation of live virus challenge dose.
AB  - Foot-and -mouth disease to pigs is serious recently around the world.
      "Vaccination prevention" is still an important policy. OIE specifies 10,000
      TCID50(0.2 ml) of virulent virus for challenge test in pigs to test the potency
      of FMD vaccine by intradermal route inoculating the virus in the heel bulbs of
      one foot or by intramuscular route administering into one site of the neck behind
      the ear. Convenience and speediness are available in the process of potency test
      of commercial FMD vaccine. We selected the route of "administering into one site
      of the muscular part of the neck behind the ear" because of convenience and
      speediness. However, it was difficult to infect control pigs even up to
      100,000TCID50, so we changed the challenged virus from cell-passaged strain to
      suckling mice-passaged one, measured its PID50 (pigs median infected dose) and
      defined the virus challenge dose as 1000PID50. Meanwhile, we arranged the number
      of control pigs from two to three for easy evaluation.

PMID- 20822548
TI  - Surgical outcomes of borderline breast lesions detected by needle biopsy in a
      breast screening program.
AB  - BACKGROUND: The Australian Capital Territory and South East New South Wales
      branch of BreastScreen Australia (BreastScreen ACT&SENSW) performs over 20,000
      screening mammograms annually. This study describes the outcome of surgical
      biopsies of the breast performed as a result of a borderline lesion being
      identified after screening mammography and subsequent workup.A secondary aim was
      to identify any parameters, such as a family history of breast cancer, or
      radiological findings that may indicate which borderline lesions are likely to be
      upgraded to malignancy after surgery. METHODS: From a period of just over eight
      years, all patients of BreastScreen ACT&SENSW who were diagnosed with a
      borderline breast lesion were identified. These women had undergone needle biopsy
      in Breastscreen ACT&SENSW and either atypical ductal hyperplasia (ADH), flat
      epithelial atypia (FEA), atypical lobular hyperplasia (ALH), radial scar/complex
      sclerosing lesion, papillary lesion, mucocoele-like lesion (MLL) or lobular
      carcinoma in situ (LCIS) was found. Final outcomes for each type of borderline
      lesion after referral for surgical biopsy were recorded and analysed. Results of
      the surgical biopsy were compared to the type of needle biopsy and its result,
      radiological findings and family history status. RESULTS: Of the 94 surgical
      biopsies performed due to the presence of a borderline breast lesion, 20% showed
      benign pathology, 55% remained as borderline lesions, 17% showed non-invasive
      malignancy and 7% showed invasive malignancy. VALCS biopsy was the most common
      needle biopsy method used to identify the lesions in this study (76%). Malignant
      outcomes resulted from 24% of the surgical biopsies, with the most common
      malignant lesion being non-comedo ductal carcinoma in situ (DCIS). The most
      common borderline lesion for which women underwent surgical biopsy was ADH (38%).
      Of these women, 22% were confirmed as ADH on surgical biopsy and 47% with a
      malignancy. CONCLUSIONS: Further research is required to determine whether
      characteristics of the mammographic lesion (particularly calcification patterns),
      the area targeted for biopsy and number of core samples retrieved, can indicate a
      closer correlation with eventual pathology. This study identified no findings in
      the diagnostic assessment that could exclude women with borderline lesions from
      surgical biopsy.

PMID- 20822549
TI  - Hypocrea jecorina CEL6A protein engineering.
AB  - The complex technology of converting lignocellulose to fuels such as ethanol has
      advanced rapidly over the past few years, and enzymes are a critical component of
      this technology. The production of effective enzyme systems at cost structures
      that facilitate commercial processes has been the focus of research for many
      years. Towards this end, the H. jecorina cellobiohydrolases, CEL7A and CEL6A,
      have been the subject of protein engineering at Genencor. Our first rounds of
      cellobiohydrolase engineering were directed towards improving the thermostability
      of both of these enzymes and produced variants of CEL7A and CEL6A with apparent
      melting temperatures above 70 degrees C, placing their stability on par with that
      of H. jecorina CEL5A (EG2) and CEL3A (BGL1). We have now moved towards improving
      CEL6A- and CEL7A-specific performance in the context of a complete enzyme system
      under industrially relevant conditions. Achievement of these goals required
      development of new screening strategies and tools. We discuss these advances
      along with some results, focusing mainly on engineering of CEL6A.

PMID- 20822550
TI  - Identification of an effective siRNA target site and functional regulatory
      elements, within the hepatitis B virus posttranscriptional regulatory element.
AB  - BACKGROUND: Infection with hepatitis B virus (HBV) is major public health
      concern. The limitations of available antiviral drugs require development of
      novel approaches to inhibit HBV replication. This study was conducted to identify
      functional elements and new siRNA target sites within the highly conserved
      regions of the 533 base post-transcriptional regulatory element (PRE) of HBV
      RNAs. RESULTS: Computational analysis of the PRE sequence revealed several
      conserved regulatory elements that are predicted to form local secondary
      structures some of these within known regulatory regions. A deletion analysis
      showed that sub-elements of the PRE have different effects on the reporter
      activity suggesting that the PRE contains multiple regulatory elements. Conserved
      siRNA targets at nucleotide position 1317-1337 and 1329-1349 were predicted.
      Although the siRNA at the position 1329-1349 had no effect on the expression of
      reporter gene, the siRNA target site at the position 1317-1337 was observed to
      significantly decrease expression of the reporter protein. This siRNA also
      specifically reduced the level of cccDNA in transiently HBV infected cells.
      CONCLUSION: The HBV PRE is likely to contain multiple regulatory elements. A
      conserved target within this region at 1317-1337 is an effective siRNA target.

PMID- 20822551
TI  - Prevalence of Chlamydia infection among women visiting a gynaecology outpatient
      department: evaluation of an in-house PCR assay for detection of Chlamydia
      trachomatis.
AB  - BACKGROUND: Screening women for Chlamydia trachomatis infection in developing
      countries is highly desirable because of asymptomatic infection. The existing
      diagnostic methods in developing countries are not effective and their
      sensitivity fall below 45.0% which leads to further spread of infection. There is
      an urgent need for improved and cost effective diagnostic tests that will reduce
      the burden of sexually transmitted infections in the developing world. METHODS:
      Prevalence of C. trachomatis infection among women visiting gynaecology
      department of Hindu Rao hospital in Delhi, India was determined using Roche
      Amplicor Multi Well Plate kit (MWP) as well as using in-house PCR assay. We used
      593 endocervical swabs for clinical evaluation of the in-house developed assay
      against Direct Fluorescence Assay (DFA; Group I n = 274) and Roche Amplicor MWP
      kit (Group II, n = 319 samples) and determined the sensitivity, specificity,
      positive predictive value (PPV), negative predictive value (NPV) of the in-house
      developed assay. RESULTS: We detected 23.0% positive cases and there was a higher
      representation of women aged 18-33 in this group. An in-house PCR assay was
      developed and evaluated by targeting unique sequence within the gyrA gene of C.
      trachomatis. Specificity of the reaction was confirmed by using genomic DNA of
      human and other STI related microorganisms as template. Assay is highly sensitive
      and can detect as low as 10 fg of C. trachomatis DNA. The resolved sensitivity of
      in-house PCR was 94.5% compared with 88.0% of DFA assay. The high specificity
      (98.4%) and sensitivity (97.1%) of the in-house assay against Roche kit and
      availability of test results within 3 hours allowed for immediate treatment and
      reduced the risk of potential onward transmission. CONCLUSIONS: The in-house PCR
      method is cost effective (~ 20.0% of Roche assay) and hence could be a better
      alternative for routine diagnosis of genital infection by C. trachomatis to
      facilitate improved screening and treatment management.

PMID- 20822552
TI  - Media coverage of health issues and how to work more effectively with
      journalists: a qualitative study.
AB  - BACKGROUND: The mass media has enormous potential to influence health-related
      behaviours and perceptions. Much research has focused on how the media frames
      health issues. This study sought to explore how journalists in Australia select
      and shape news on health issues. METHODS: The study involved semi-structured
      interviews with 16 journalists from major Australian print, radio and television
      media organisations reporting on avian influenza and pandemic planning.
      Journalists, including reporters, editors and producers, were interviewed between
      October 2006 and August 2007. Thematic analysis was used to draw out major
      lessons for health communicators. RESULTS: Journalists routinely attempted to
      balance different, sometimes competing, aims amidst significant operational
      constraints. They perceived the most trusted sources on health issues to be
      respected and independent doctors. Specialist health and medical reporters had a
      more sound technical knowledge, channels to appropriate sources, power within
      their organisations, and ability to advocate for better quality coverage.
      CONCLUSIONS: An awareness of how to work with the media is essential for health
      communicators. This includes understanding journalists' daily routines, being
      available, providing resources, and building relationships with specialist health
      reporters.

PMID- 20822553
TI  - New genetic links in eosinophilic esophagitis.
AB  - Eosinophilic esophagitis (EoE) is increasingly diagnosed as a disorder throughout
      the world. It is characterized by eosinophils in the esophagus due to food
      allergies. Molecular analysis of esophageal biopsies and mouse models have
      indicated a clear role for the T helper 2 pathway, in particular interleukins 5
      and 13, in this disease. Current treatment options for EoE involve avoidance of
      the allergens or using anti-inflammatory medications such as topical
      corticosteroids. In the past year, genomic research has led to the identification
      of single nucleotide polymorphisms in the gene encoding thymic stromal
      lymphopoietin (TSLP), and subsequently in the gene encoding its receptor, as
      disease susceptibility markers for EoE. Identification of this molecule and its
      receptor suggest the potential for new treatment options in the future.

PMID- 20822554
TI  - Drugs targeting Bcl-2 family members as an emerging strategy in cancer.
AB  - Inhibiting apoptosis is widely accepted as a necessary step in the transition
      from normal to cancer cells, and most cancer therapies exert their effects by
      indirectly reversing this process. Commitment to apoptosis is caused by
      permeabilisation of the outer mitochondrial membrane--a process regulated by the
      binding between different members of the Bcl-2 family. Furthermore, Bcl-2 family
      members also bind to the endoplasmic reticulum, where they modify processes such
      as the unfolded-protein response and autophagy that also cause or modify
      different types of cell death. With the growing understanding of the importance
      of the Bcl-2 family as crucial regulators of the decision to initiate apoptosis,
      much effort has been directed at developing small molecules that modify function
      by directly binding to Bcl-2 proteins. Preclinical experiments have confirmed
      that these agents kill cancer cells and overcome chemotherapy resistance. Two of
      these drugs are in the initial stages of clinical development (ABT-263 and
      obatoclax), and early results show clinical efficacy at tolerable doses.
      Important questions for the future include the role of these drugs as monotherapy
      versus combination therapy with other anticancer drugs, and the related issue of
      the relative toxicity to cancerous versus normal cells.

PMID- 20822555
TI  - Basic bio-ecological parameters of the invasive red palm weevil, Rhynchophorus
      ferrugineus (Coleoptera: Curculionidae), in Phoenix canariensis under
      Mediterranean climate.
AB  - The invasive red palm weevil, Rhynchophorus ferrugineus Olivier (Coleoptera,
      Curculionidae), is one of the most destructive pests of palms in the world. Since
      its detection in the Mediterranean Basin, the ornamental Phoenix canariensis
      Hort. ex Chabaud has become its main host. This study was aimed at determining
      the life cycle of R. ferrugineus in live P. canariensis palms. Egg lethal
      temperature threshold and thermal constant were determined in the laboratory and
      resulted in 13.1 degrees C and 40.4 degree days (DD), respectively. A semi field
      assay was carried out in a mesh enclosure where living P. canariensis palms were
      artificially infested with neonate larvae at one-month intervals from June 2008
      to May 2009 under natural conditions. Infested palms were dissected at different
      time intervals. Maximum mortality rates for R. ferrugineus were observed for
      palms infested either in December or January (100%), whereas those infested from
      April through September showed maximum survival rates. Mean monthly temperatures
      below 10.3 degrees C were lethal for neonate larvae, as 4.5 degrees C were for
      older immature stages. All recovered larvae could be classed according to one of
      13 instars. A thermal constant of 666.5 DD was estimated for complete larval
      development. Pupal develoment required an additional 282.5 DD. Based on these
      results and on the temperatures from 46 climatic stations selected in the Iberian
      Peninsula, less than one generation per year can be expected in areas with mean
      annual temperature below 15 degrees C and more than two where mean annual
      temperature is above 19 degrees C.

PMID- 20822556
TI  - Distribution and dynamics of Bemisia tabaci invasive biotypes in central China.
AB  - The tobacco whitefly, Bemisia tabaci (Gennadius), causes severe crop losses in
      many agricultural systems. The worst of these losses are often associated with
      the invasion and establishment of specific whitefly biotypes. In a comprehensive
      survey of biotypes present in central China between 2005 and 2007, we obtained
      191 samples of B. tabaci from 19 districts in Hubei province and its surrounds.
      Biotypes were identified by RAPD-PCR and by sequencing the mitochondrial
      cytochrome oxidase I gene (mtCO1). We determined that these central Chinese
      haplotypes included the world's two most invasive B. tabaci biotypes (B and Q)
      and two indigenous biotypes (ZHJ1 and ZHJ3). The B biotype shared >99.7% identity
      with other Chinese B biotypes and the Q biotype shared >99.5% of its identity
      with Q samples from the Mediterranean, USA, Africa and East Asia. By 2007, the Q
      biotype was dominant over much of Hubei province and appeared to be supplanting
      all other biotypes, although both the invasive and indigenous biotypes existed in
      sympatry in some regions. The invasion and rapid establishment of the Q biotype
      in China mirrors events elsewhere in the world, and we suggest that this is a
      consequence of its reproductive isolation, its polyphagous nature and its broad
      spectrum resistance to insecticides. Its dominance has severe implications for
      the sustainability of some insecticide groups and for the production of a number
      of crops.

PMID- 20822557
TI  - Association of production factors with milk IgA and IgM concentrations in normal
      lactating cows.
AB  - Concentrations of IgA and IgM in milk from normal lactating cows were measured to
      determine whether they were affected by lactation number, lactation stage, daily
      milk production, milk composition and somatic cell score (SCS). A total of 284
      Chinese Holstein cows showing no signs of mastitis were selected from more than
      1600 cows from one farm. Concentrations of IgA and IgM in normal milk were
      determined by ELISA. Results revealed that average milk IgA and IgM
      concentrations were 235+/-11 and 32+/-3 MUg/ml, respectively. IgA and IgM
      concentrations in milk were found to have an association with lactation number,
      stage of lactation, daily milk production and SCS. Both SCS and daily milk
      production were found to be strong significant (P<0.01) direct factors
      correlating to IgA concentration. Stage of lactation and SCS were found to be
      strong significant (P<0.01) direct factors correlating to IgM concentration.

PMID- 20822558
TI  - Immune response of bovine milk somatic cells to endotoxin in healthy quarters
      with normal and very low cell counts.
AB  - Low somatic cell count (SCC) is a reliable indicator of high-quality milk free of
      pathogenic microorganisms. Thus, an important goal in dairy practice is to
      produce milk with low SCC. Selection for cows with low SCC can sometimes lead to
      extremely low SCC in single quarters. The cells in milk are, however,
      predominantly immune cells with important immune functions. To investigate the
      mammary immune competence of quarters with very low SCC, healthy udder quarters
      of cows with normal SCC of (40-100) x 103 cells/ml and very low SCC of < 20 x 103
      cells/ml were challenged with lipopolysaccharide (LPS) from Escherichia coli. In
      the first experiment, SCC and cell viability after a challenge with 50 ng of
      LPS/quarter was investigated. In the second experiment, tumour necrosis factor
      alpha (TNF-alpha) concentration and lactate dehydrogenase (LDH) activity in milk,
      and mRNA expression of various innate immune factors in milk cells were measured
      after a challenge with 100 MUg LPS/quarter. LPS challenge induced an increase of
      SCC. SCC levels reached were higher in quarters with normal SCC and maximum SCC
      was reached 1 h earlier than in very low SCC quarters. The increase of TNF-alpha
      concentrations in milk in response to LPS challenge was lower in quarters with
      very low SCC than in quarters with normal SCC. The viability of cells and the LDH
      activity in milk increased in response to LPS challenge, however, without a
      difference between the groups. The mRNA expression of IL-1beta and IL-8 was
      increased in milk cells at 12 h after LPS challenge, whereas that of TNF-alpha
      and lactoferrin was not increased at the measured time points (12, 24 and 36 h
      after LPS challenge). No differences of mRNA expression of measured immune
      factors between normal and very low SCC samples were detected. The study showed
      that udder quarters with very low SCC responded with a less marked increase of
      SCC compared with quarters with normal SCC. This difference corresponded with
      simultaneously lower TNF-alpha concentrations in milk. However, the immune
      competence of the cells themselves based on mRNA expression of TNF-alpha, IL-8,
      IL-1beta, and lactoferrin, did not differ. The results may indicate that very low
      SCC can impair the immune competence of udder quarters, because the immune
      response in udder quarters with lower SCC is less efficient as fewer cells
      contribute to the production of immunoregulators.

PMID- 20822559
TI  - Teat anatomy affects requirements for udder preparation in Mediterranean
      buffaloes.
AB  - The present study was conducted to assess the interrelation between teat anatomy
      and machine milking in dairy buffaloes raised in Switzerland. A 3-min pre
      stimulation induced milk ejection before cluster attachment in most cases and
      caused an optimal milk removal during machine milking. In an additional
      experiment, longitudinal cross-section ultrasound was obtained before and after a
      3-min pre-stimulation. Teat wall thickness, teat diameter, cisternal diameter and
      teat canal length were evaluated. It was observed that 3-min pre-stimulation
      dramatically reduced teat canal length whereas all the other anatomical
      parameters remained unchanged. The vacuum needed to open the teat canal was also
      measured before and after a 3-min pre-stimulation by using a special teat cup
      with only the mouthpiece of the liner remaining on the top of the teat cup (no
      liner, no pulsation). Without pre-stimulation but after wetting the teat canal by
      stripping one squirt of milk out of the teat, no milk could be withdrawn with a
      vacuum up to 39 kPa. However, after pre-stimulation, milk flow occurred in all
      buffaloes at a vacuum between 16 and 38 kPa. In the last experiment, the teat
      tissue was examined in slaughtered buffaloes and compared with teat tissue of
      cows. No difference was noted in histological sections and teat canal length was
      similar in cows and buffaloes. Proximal to the teat canal, the teat did not pass
      into an open cistern but the lumen was collapsed. In conclusion, buffaloes need
      to be well pre-stimulated because the tissue above the teat canal provides
      additional teat closure before milk ejection. Therefore, milk can only be
      obtained after pre-stimulation.

PMID- 20822560
TI  - Effects of divergent Holstein-Friesian strain and diet on diurnal patterns of
      plasma metabolites and hormones.
AB  - Commonly measured metabolite and hormone concentrations used to describe the
      metabolic status of lactating cows undergo diurnal variation resulting in
      distinct patterns. Studies have shown that feeding events can modulate these
      diurnal patterns as cows respond to the nutrient intake. What is less clear is
      the extent to which cow genetics and diet interact to modify the diurnal patterns
      of specific nutritionally related metabolites and hormones. The objective of this
      study was to investigate diurnal patterns in circulating metabolite and hormone
      concentrations in divergent strains of Holstein-Friesian cows (North American,
      NA; and New Zealand, NZ) offered either fresh pasture (FP) or a total mixed
      ration (TMR). Plasma concentrations of growth hormone (GH), insulin-like growth
      factor-1 (IGF-1), glucose, insulin, beta-hydroxybutyrate (BHBA), and non
      esterified fatty acids (NEFA) were determined at 4-h intervals for a minimum of
      three consecutive days. All of the above metabolites and hormones exhibited
      within-day variability. Main effects of genetic strain and diet were observed for
      plasma IGF-1, and a strain by diet interaction was observed for GH. Time of day x
      diet interactions were observed for both glucose and insulin. Three-way
      interactions (time of day x diet x strain) were observed for BHBA and NEFA. These
      data indicate different levels of diurnal variation, with glucose, insulin, NEFA
      and BHBA having the largest daily variation. These diurnal patterns need to be
      considered in future investigations of these metabolites and hormones.

PMID- 20822561
TI  - Assessment of epithelial cells' immune and inflammatory response to
      Staphylococcus aureus when exposed to a macrolide.
AB  - Non-specific (innate) immune response plays a major role in defending the udder
      from bacterial invasion. Moreover, recent investigations suggest that mammary
      gland epithelial cells (MGEC) could have a large and important role as a source
      of soluble components of immune defences. Despite many attempts to find other
      ways to control/prevent mastitis (i.e. vaccine) antimicrobial therapy is still
      the most used and effective means of curing clinical and subclinical mastitis.
      However, drug concentrations and therapy durations are far from the optimal in
      order to reduce costs. Therefore, efficacy of antimicrobial therapy is dependent
      not only on the substance activity but also on the positive interactions with the
      host innate immune response. Surprisingly, information on these interactions is
      rather scarce in the mastitis field. A simple experimental model was developed
      based on BME-UV cell line, Staphylococcus aureus as a challenge and a macrolide
      as an antimicrobial to assess the interactions among epithelial cells, Staph.
      aureus and the potential effects of antimicrobials on the immune system. The
      results of this study confirmed that tylosin has good antimicrobial activity
      against both intracellular and extracellular Staph. aureus in bovine MGEC without
      affecting cell functions. In this study, a significant down-regulation of IL-1
      and IL-6 was observed, while TNF and IL-8 expression rate numerically increased,
      but differences were not significant. To our knowledge, this is the first paper
      assessing the concentration of two lysosomal enzymes, lysozyme and N-acetyl-beta
      d-glucosaminidase (NAGase), in Staph. aureus-stimulated MGEC. The results of this
      study confirmed that tylosin could have a significant effect on the release of
      these enzymes. Moreover, even if both enzymes have a similar substrate as a
      target, the results suggest different secretion mechanisms and an influence of
      antimicrobial treatment on these mechanisms. Successful mastitis cure is the
      result of achieving the optimal efficiency of both innate immune defences and
      therapeutical activities, by means of killing bacteria without eliciting an
      excessive inflammatory response. Therefore, antimicrobials for mastitis therapy
      should be selected not only on bacterial sensitivity, but also for their positive
      interactions with the innate immune response of the mammary gland. This study
      showed that an in-vitro model based on Staph. aureus challenge on MGEC could be
      helpful in assessing both the intracellular and extracellular activity of
      antimicrobials and their influence on epithelial cell immune and inflammatory
      response.

PMID- 20822562
TI  - Efficacy of homeopathic and antibiotic treatment strategies in cases of mild and
      moderate bovine clinical mastitis.
AB  - The objective of this clinical control trial was to examine the effectiveness of
      the classical homeopathic treatment strategy in cases of mild and moderate bovine
      clinical mastitis in comparison with antibiotic and placebo treatments. Owing to
      characteristics of the selected herds, only cases of clinical mastitis caused by
      environmental pathogens and clinical cases with negative bacteriological result
      in the pre-treatment milk sample were included in the trial. A total of 136
      lactating dairy cows with 147 affected quarters from four herds in Germany were
      randomly allocated to three treatment groups. The cows were examined on days 0,
      1, 2 and on days 7, 14, 28 and 56 post initial infection to assess clinical
      signs. Simultaneously, with the exception of days 1 and 2, quarter milk samples
      for laboratory examinations (bacteriology, somatic cell count) were collected to
      assess bacteriological and cytological cure rates. On days 28 and 56, treatment
      strategies did not differ significantly with respect to the clinical outcomes and
      the total cure rate in cases of bacteriological negative mastitis (n=56). In
      cases of pathogen-positive mastitis (n=91), the cure rate after 4 and 8 weeks was
      similar between the two treatment strategies, homeopathy and antibiotic
      treatment, but the difference between the homeopathic and the placebo treatment
      at day 56 was significant (P<0.05). The results indicate a therapeutic effect of
      homeopathic treatment in cases of mild and moderate clinical mastitis. However,
      independent of treatment strategy and bacteriological status, the total cure rate
      was on a low level, revealing limitations in the effectiveness of both antibiotic
      and homeopathic treatment strategies.

PMID- 20822563
TI  - Single nucleotide polymorphisms at the imprinted bovine insulin-like growth
      factor 2 (IGF2) locus are associated with dairy performance in Irish Holstein
      Friesian cattle.
AB  - The imprinted insulin-like growth factor 2 gene (IGF2) encodes a fetal mitogenic
      hormone protein (IGF-II) and has previously been shown to be associated with
      performance in dairy cattle. In this study we assessed genotype-phenotype
      associations between four single nucleotide polymorphisms (SNPs) located within
      the bovine IGF2 locus on chromosome 29 and a range of performance traits related
      to milk production, animal growth and body size, fertility and progeny survival
      in 848 progeny-tested Irish Holstein-Friesian sires. Two of the four SNPs
      (rs42196909 and IGF2.g-3815A>G), which were in strong linkage disequilibrium (r2
      = 0.995), were associated with milk yield (P <= 0.01) and milk protein yield (P
      <= 0.05); the rs42196901 SNP was also associated (P <= 0.05) with milk fat yield.
      Associations (P <= 0.05) with milk fat percentage and milk protein percentage
      were observed at the rs42196901 and IGF2.g-3815A>G SNPs, respectively. The
      rs42196909 and IGF2.g-3815A>G SNPs were also associated with progeny carcass
      conformation (P <= 0.05), while an association (P <= 0.01) with progeny carcass
      weight was observed at the rs42194733 SNP locus. None of the four SNPs were
      associated with body size, fertility and progeny survival. These findings support
      previous work which suggests that the IGF2 locus is an important biological
      regulator of milk production in dairy cattle and add to an accumulating body of
      research showing that imprinted genes influence many complex performance traits
      in cattle.

PMID- 20822564
TI  - Fluorometric determination of uric acid in bovine milk.
AB  - The primary objective of this study is to validate a new fast method for
      determination of uric acid in milk. The method is based on an enzymatic
      fluorometric technique that requires minimal pre-treatment of milk samples. The
      present determination of uric acid is based on the enzymatic oxidation of uric
      acid to 5-hydroxyisourate via uricase where the liberated hydrogen peroxide
      reacts with 10-acetyl-3,7-dihydroxyphenoxazine via peroxidase and the fluorescent
      product, resorufin, is measured fluorometrically. Fresh composite milk samples
      (n=1,072) were collected from both Jersey (n=38) and Danish Holstein (n=106) cows
      from one local herd. The average inter- and intra-assay variations were 7.1% and
      3.0%, respectively. Percent recovery averaged 103.4, 107.0 and 107.5% for samples
      spiked with 20, 40 or 60 MUm of standard, respectively, with a correlation
      (r=0.98; P<0.001) observed between the observed and expected uric acid
      concentrations. A positive correlation (r=0.96; P<0.001) was observed between
      uric acid concentrations using the present method and a reference assay. Storage
      at 4 degrees C for 24 h resulted in lower (P<0.01) uric acid concentrations in
      milk when compared with no storage or samples stored at -18 degrees C for 24 h.
      Addition of either allopurinol (a xanthine oxidase inhibitor) or
      dimethylsulfoxide (a solvent for allopurinol) did not affect milk uric acid
      concentrations (P=0.96) and may indicate that heat treatment before storage and
      analysis was sufficient to degrade xanthine oxidase activity in milk. No
      relationship was observed between milk uric acid and milk yield and milk
      components. Authors recommend a single heat treatment (82 degrees C for 10 min)
      followed by either an immediate analysis of fresh milk samples or storage at -18
      degrees C until further analysis.

PMID- 20822565
TI  - Influenza virus A subtype H1N1 is inhibited by methylated beta-lactoglobulin.
AB  - Addition of methylated beta-lactoglobulin (Met-BLG) in the medium of MDCK cell
      lines infected with influenza virus subtype H1N1 reduced hemagglutination
      activity (HA) in a concentration dependent manner. Antiviral activity of Met-BLG
      depended on its concentration, viral load, and duration of infection. Using 17
      MUg/ml of Met-BLG inhibited 50% of HA of H1N1 grown in MDCK cells at 1 MOI after
      24 h incubation at 37 degrees C and in 5% CO2. Extension of incubation time
      enhanced antiviral action since the same concentration of Met-BLG inhibited about
      61% of viral activity after 48 h. This viral inhibition was accompanied by a
      protection of MDCK cells as observed by using neutral red or by direct microscope
      examination. Reduction of viral RNA replication upon the addition of Met-BLG (50
      MUg/ml) was observed by real time-PCR showing a reduction of viral log value of
      about 0.9. When viral stock solution was mixed with 25 MUg/ml Met-BLG in absence
      of cell lines, the morphology and viability of virus particles were significantly
      affected as observed by electron microscopy, and the number of intact virus
      particles was reduced by roughly 65%.

PMID- 20822566
TI  - Observed reduction in recovery of Corynebacterium spp. from bovine milk samples
      by use of a teat cannula.
AB  - Although Corynebacterium bovis and coagulase-negative staphylococci are
      frequently the most commonly isolated bacteria from milk samples submitted for
      identification of pathogens causing intramammary infection, the individual
      quarter somatic cell count (SCC) from those samples is most often low. The
      present study aimed at evaluating the difference in bacteriology results from
      milk sampled by the standard technique (as recommended by the National Mastitis
      Council) and by the use of a teat cannula surpassing the teat canal, since C.
      bovis is often only found in the teat canal. Single quarter milk samples were
      collected in duplicate from 132 dairy cows on a commercial dairy farm using the
      standard milk sampling technique and also using a cannula introduced into the
      teat. Two groups of quarters were sampled: a group that was selected randomly at
      cow and quarter level and a group that was selected based on having SCC >200,000
      cells/ml at the previous milk recording at cow level and on California mastitis
      test result at quarter level. Bacteriological culture performed on the samples
      yielded 29 Corynebacterium spp. isolates from the samples collected with the
      standard technique and 6 isolates from the samples collected with a cannula.
      Bacteriological culture yielded 73 and 100 culture negative samples respectively
      with the standard and the alternative sampling technique. A significant
      difference between the two sampling techniques was observed for recovery of
      Corynebacterium spp. and for no-growth samples. There was no significant
      difference in the isolation of Corynebacterium spp. or other bacterial species
      when using the standard technique before or after sampling with the cannula; thus
      the observed difference in bacteriology results could not be attributed to a
      particular sampling order. No significant change was observed overall in
      individual quarter SCC measured on the sampling day and 7 d later. Our results
      agree with several studies showing that Corynebacterium bovis often colonizes the
      teat canal, without causing true intramammary infection.

PMID- 20822567
TI  - Effect of freeze-drying on viability and in vitro probiotic properties of a
      mixture of lactic acid bacteria and yeasts isolated from kefir.
AB  - The effect of freeze-drying on viability and probiotic properties of a microbial
      mixture containing selected bacterial and yeast strains isolated from kefir
      grains (Lactobacillus kefir, Lactobacillus plantarum, Lactococcus lactis,
      Saccharomyces cerevisiae and Kluyveromyces marxianus) was studied. The
      microorganisms were selected according to their potentially probiotic properties
      in vitro already reported. Two types of formulations were performed, a microbial
      mixture (MM) suspended in milk and a milk product fermented with MM (FMM). To
      test the effect of storage on viability of microorganisms, MM and FMM were freeze
      dried and maintained at 4 degrees C for six months. After 180 days of storage at
      4 degrees C, freeze-dried MM showed better survival rates for each strain than
      freeze-dried FMM. The addition of sugars (trehalose or sucrose) did not improve
      the survival rates of any of the microorganisms after freeze-drying. Freeze
      drying did not affect the capacity of MM to inhibit growth of Shigella sonnei in
      vitro, since the co-incubation of this pathogen with freeze-dried MM produced a
      decrease of 2 log in Shigella viability. The safety of freeze-dried MM was tested
      in mice and non-translocation of microorganisms to liver or spleen was observed
      in BALB/c mice feed ad libitum during 7 or 20 days. To our knowledge, this is the
      first report about the effect of freeze-drying on viability, in vitro probiotic
      properties and microbial translocation of a mixture containing different strains
      of both bacteria and yeasts isolated from kefir.

PMID- 20822568
TI  - Characterization of lactoferrin oil-in-water emulsions and their stability in
      recombined milk.
AB  - Emulsions were prepared with 20% soy oil and different concentrations of
      lactoferrin, and tested at pH values from 3 to 7.5. The stability of the
      emulsions decreased as the pH got closer to the isoelectric point of the protein.
      A concentration of 1% lactoferrin was determined to be sufficient to provide full
      coverage of the emulsion droplets. Lactoferrin-stabilized emulsions were then
      prepared in water at pH 6.6 and their behaviour when added to reconstituted milk
      was studied. It was observed that lactoferrin emulsions were stable when
      reconstituted in milk, but they showed aggregation when diluted in milk serum
      alone. The destabilization was caused by shielding of the charges on the surface
      of the oil droplets. Stabilization in milk occurred due to interactions at the
      interface with other soluble proteins. In fact, when beta-lactoglobulin or sodium
      caseinate were added to the serum, stability of the emulsion droplets was
      restored, indicating that these proteins were able to adsorb at the interface and
      aid in the stabilization. Since zeta-potential measurements did not show
      significant overall charge on the emulsion droplets, this suggests that the
      stabilization forces are not only electrostatic in nature, but that there are
      other mechanisms at play.

PMID- 20822569
TI  - In situ generation of milk protein-derived peptides in drying-off cows.
AB  - Our previous studies demonstrated prompt elevation of proteinase activity in
      mammary secretion of drying-off cows and goats. The current study examined the
      progressive changes in composition of cow mammary secretion following drying-off
      and, in parallel, characterized the mode of peptide neogenesis using matrix
      assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF
      MS) and liquid chromatography-electrospray-ionization (LC-ESI) MS/MS. The results
      show that the percentage of casein of total milk protein at time of drying-off
      was 76%, which dropped to 41%, 24%, and 16%, respectively, 1, 2, and 3 weeks
      after drying-off. Levels of beta-lactoglobulin and alpha-lactoalbumin in mammary
      secretions of drying-off cows decreased prominently while levels of lactoferrin,
      BSA, and casein derived-proteins increased concomitantly compared with regular
      milk. A fractionation procedure was applied to remove molecules larger than 10
      kDa before MALDI-TOF MS and LC-ESI MS/MS and the results show that the MALDI-TOF
      MS peptide profile of mammary secretion ranging from m/z 600 to 4000 was
      apparently modified after drying-off for 1 week, whereas species 1590 m/z and
      2460 m/z were most obviously enriched compared with regular milk. LC-ESI MS/MS
      results were used to map peptide sequence with Mascot search server and under no
      post translational modification to reduce database size and 202 novel beta-casein
      derived peptides were successfully identified in mammary secretion after drying
      off for 1 week in contrast to regular milk. Accordingly at least 48 additional
      cleavage positions were assigned on beta-casein for mammary secretion. Among the
      202 novel peptides, 5 are homologous with confirmed opioid agonists, angiotensin
      1-converting enzyme inhibitors, or immuno-modulators. In conclusion, peptides are
      released in situ from milk proteins within short intervals following drying-off
      in cows. They might play roles in the transition of mammary glands from lactating
      to non-lactating. With specified post-translational modifications and focused
      functional screening, novel peptides are yet to be discovered in dry cow mammary
      secretion.

PMID- 20822570
TI  - Measurement of thyroid hormones in donkey (Equus asinus) blood and milk:
      validation of ELISA kits and evaluation of sample collection, handling and
      storage.
AB  - Donkey's milk is well tolerated by human infants with cow's milk allergy and is
      useful in the treatment of human immune-related diseases and in the prevention of
      atherosclerosis. Thyroid hormones (TH) stimulate lactation and active
      triiodothyronine (T3) in colostrum and milk could take paracrine action
      supporting lactogenesis in the mother, and play physiological roles for the
      suckling offspring (systemic or within the gastrointestinal tract). The aims were
      to measure TH concentrations in donkey blood and milk, validate ELISA methods,
      evaluate the effects of sample collection and post-collection handling and the
      stability of TH in milk and blood serum and plasma samples. In milk and blood
      samples obtained from lactating jennies total concentrations of TH were assayed
      using competitive-type ELISA kits. Good validation results were obtained for both
      TH concentrations in blood serum and plasma and T3 in milk samples extracted with
      cold (-20 degrees C) ethanol alkalinized (pH 9.0) with NH4OH. In most of the milk
      extract samples, thyroxine (T4) concentrations resulted below the sensitivity
      threshold. Intra- and inter-assay coefficients of variations of TH concentrations
      in different blood and milk samples were below 10%. Parallelism tests gave
      displacement lines parallel to those of the calibrators for both TH in blood
      serum and plasma and for T3 in milk extracts. Mean recovery rates were between
      95% and 123%, but the concentration values approaching the highest calibrators
      were overestimated. Therefore, serum and plasma samples for T3 assay must be
      previously diluted with buffer. Both TH concentrations in blood serum and plasma
      and T3 in milk did not change during storage for up to 6 months at -20 degrees C.
      In conclusion, the ELISA methods tested in the present study are suitable for
      determination of both TH concentrations in donkey blood samples, and for T3
      measurement in milk, after extraction with cold alkaline ethanol.

PMID- 20822571
TI  - Rapid and direct quantitative detection of viable bifidobacteria in probiotic
      yogurt by combination of ethidium monoazide and real-time PCR using a molecular
      beacon approach.
AB  - The potential of ethidium monoazide (EMA) real-time PCR method based on molecular
      beacon probe for rapid detection of viable bifidobacteria present in probiotic
      yogurt was evaluated in this work. A real-time PCR with molecular beacon assay
      was developed to determine genus Bifidobacterium quantitatively in order to
      increase the sensitivity and specificity of assay. EMA was used to treat
      probiotic yogurt prior to DNA extraction and real-time PCR detection to allow
      detection of only viable bacteria. The primer set of Bif-F/Bif-R which is genus
      specific for Bifid. was designed. The specificity of the probes ensures that no
      signal is generated by non-target amplicons. Linear regression analysis
      demonstrated a good correlation (R2 = 0.9948) between the EMA real-time PCR
      results and the plate counting, and real-time quantitative PCR results correlated
      adequately with enumeration of bifidobacteria by culture for commercial probiotic
      yogurt. This culture-independent approach is promising for the direct and rapid
      detection of viable bifidobacteria in commercial probiotic yogurt, and the
      detection can be carried out within 4 h. The detection limit for this method is
      about 104 cell/ml. In conclusion, the direct quantitative EMA real-time PCR assay
      based on molecular beacon described in this research is a rapid and quantitative
      method.

PMID- 20822572
TI  - Composition of poorly and non-coagulating bovine milk and effect of calcium
      addition.
AB  - Ninety-nine individual milk samples from 37 cows in lactation week 10-35,
      selected for producing well or poorly/non-coagulating milk, were compared
      regarding protein composition, total calcium content, casein micelle size, pH,
      and coagulating properties after addition of 0.05% CaCl2. The results showed that
      a low kappa-casein concentration in milk was a risk factor for non-coagulation.
      CaCl2 addition improved coagulating properties (coagulation time, curd firmness)
      of nearly all samples and eliminated differences between poorly/non-coagulating
      and well-coagulating milk, particularly regarding curd firmness. A second,
      independent data set with 18 non-coagulating or well-coagulating milk samples
      were analysed for protein composition, where indications of a similar association
      with kappa-casein was observed.

PMID- 20822573
TI  - The development of rediae of Fasciola hepatica in Radix natalensis subjected
      twice to bimiracidial exposures.
AB  - Experimental infections of Egyptian Radix natalensis with a French isolate of
      Fasciola hepatica (each snail was subjected twice to a bimiracidial exposure)
      were carried out to determine how many sporocysts grew in these snails and to
      study the developmental patterns of redial generations. Single-sporocyst
      infections were found in 69.3% (34/49) of infected snails, with equivalent
      numbers of normal and abnormal patterns. Snails with two- and three-sporocyst
      infections were 24.4% and 6.1%, respectively. In single- and two-sporocyst
      infections at days 42 and 56 post-exposure, the total redial burden was
      significantly higher in snails with a normal redial development. In two- and
      three-sporocyst infections, the overall maturity of rediae was delayed at days 42
      and 56. The high frequency of abnormal patterns in R. natalensis (53.1% of all
      infected snails showed degeneration of a first mother redia) might be due to
      incomplete adaptation between the snail population and the parasite. The delayed
      redial maturity in two- and three-sporocyst infections can mainly be explained by
      the volume of the snail body, which would be insufficient to allow the
      simultaneous differentiation of most rediae over time.

PMID- 20822575
TI  - Multiple-locus variable-number tandem-repeat analysis for discriminating within
      Salmonella enterica serovar Typhimurium definitive types and investigation of
      outbreaks.
AB  - The discriminatory power of multiple-locus variable-number tandem-repeat analysis
      (MLVA) needs to be evaluated for all Salmonella enterica subspecies enterica
      serovar Typhimurium (S. Typhimurium) phage types so that the power of this
      methodology is understood and results can be interpreted correctly during
      outbreak investigations. We evaluated the ability of MLVA to characterize four
      definitive phage types (DT) problematic in New Zealand. MLVA discriminated
      between DT104 isolates although there was very limited variation in the MLVA
      profiles for isolates with an RDNC phage type (reacts but does not conform to a
      recognized Typhimurium phage pattern) first observed in New Zealand's Enteric
      Reference Laboratory in May 2006. Most DT101 isolates had indistinguishable MLVA
      profiles or profiles that differed at one or two loci. This was also observed in
      DT160 isolates. MLVA may not identify all common-source outbreaks although it
      provided valuable data when applied to case isolates from two S. Typhimurium
      outbreaks.

PMID- 20822574
TI  - The glmS ribozyme: use of a small molecule coenzyme by a gene-regulatory RNA.
AB  - The glmS ribozyme is the first known example of a natural ribozyme that has
      evolved to require binding of an exogenous small molecule for activity. In Gram
      positive bacteria, this RNA domain is part of the messenger RNA (mRNA) encoding
      the essential enzyme that synthesizes glucosamine-6-phosphate (GlcN6P). When
      present at physiologic concentration, this small molecule binds to the glmS
      ribozyme and uncovers a latent self-cleavage activity that ultimately leads to
      degradation of the mRNA. Biochemical and structural studies reveal that the RNA
      adopts a rigid fold stabilized by three pseudoknots and the packing of a
      peripheral domain against the ribozyme core. GlcN6P binding to this pre-organized
      RNA does not induce conformational changes; rather, the small molecule functions
      as a coenzyme, providing a catalytically essential amine group to the active
      site. The ribozyme is not a passive player, however. Active site functional
      groups are essential for catalysis, even in the presence of GlcN6P. In addition
      to being a superb experimental system with which to analyze how RNA catalysts can
      exploit small molecule coenzymes to broaden their chemical versatility, the
      presence of the glmS ribozyme in numerous pathogenic bacteria make this RNA an
      attractive target for the development of new antibiotics and antibacterial
      strategies.

PMID- 20822576
TI  - Geographical association between livestock density and human Shiga toxin
      producing Escherichia coli O157 infections.
AB  - Shiga toxin-producing Escherichia coli (STEC) bacteria can cause outbreaks and
      sporadic cases of gastroenteritis in humans. Ruminants are seen as the main
      reservoir. The aim of this study was to evaluate the spatial association between
      reported human STEC O157 infections in The Netherlands and different livestock
      densities. Data were collected at the municipality level and a spatial regression
      analysis was performed. Between April 1999 and December 2008, 409 symptomatic
      sporadic cases were registered. Adding an interaction term between season, age,
      and livestock density showed an increased risk of STEC cases in summer for living
      in areas with cattle, in particular for young children. In conclusion, cattle,
      but not pigs or poultry, are indicated as an important source for human STEC O157
      infections in rural areas. The association is probably due to direct or indirect
      contact with cattle, resulting in symptomatic infections, especially in young
      children.

PMID- 20822577
TI  - Environmental risk factors for haemorrhagic fever with renal syndrome in a French
      new epidemic area.
AB  - In France, haemorrhagic fever with renal syndrome (HFRS) is endemic along the
      Belgian border. However, this rodent-borne zoonosis caused by the Puumala virus
      has recently spread south to the Franche-Comte region. We investigated the space
      time distribution of HFRS and evaluated the influence of environmental factors
      that drive the hantavirus reservoir abundance and/or the disease transmission in
      this area. A scan test clearly indicated space-time clustering, highlighting a
      single-year (2005) epidemic in the southern part of the region, preceded by a
      heat-wave 2 years earlier. A Bayesian regression approach showed an association
      between a variable reflecting biomass (normalized difference vegetation index)
      and HFRS incidence. The reasons why HFRS cases recently emerged remain largely
      unknown, and climate parameters alone do not reliably predict outbreaks.
      Concerted efforts that combine reservoir monitoring, surveillance, and
      investigation of human cases are warranted to better understand the
      epidemiological patterns of HFRS in this area.

PMID- 20822579
TI  - Misplaced trust? Gaping flaws in drug registration and licensing.

PMID- 20822581
TI  - Clinical trials in South Africa: Need for capacity building and training.

PMID- 20822582
TI  - Mercury exposure in a low-income community in South Africa.

PMID- 20822583
TI  - Meckel's diverticulitis revisited.

PMID- 20822585
TI  - Gauteng MEC shifts corruption focus to healthcare workers.

PMID- 20822584
TI  - Mother and child care services 'insufficient to save lives' - HSRC report.

PMID- 20822586
TI  - Crowded wards, lousy admin contribute to death and suffering.

PMID- 20822587
TI  - Reversible nephrotic syndrome secondary to pulmonary hydatid disease.
AB  - Most patients with pulmonary hydatidosis are children. The disease may be
      asymptomatic or revealed by unusual events such as a glomerulopathy. An 8-year
      old boy from a rural part of Tunisia presented with generalised oedema and
      macroscopic haematuria. There was no familial history of renal disease. He had a
      normal blood pressure (100/60 mmHg), and a pleural effusion was detected.
      Urinalysis showed nephrotic range proteinuria (375 mg/kg/d) and microscopic
      haematuria. His serum total protein concentration was 40 g/l and his serum
      albumin was 10 g/l. Renal biopsy showed capillary wall thickening and
      duplication, and mesangial cell proliferation in the glomeruli, characteristic of
      mesangiocapillary glomerulonephritis. Renal and abdominal ultrasound images
      showed increased echogenicity of the kidneys and mild ascites. Radiology revealed
      three large pulmonary hydatid cysts. The largest cyst occupied the entire right
      upper lobe and compressed the superior vena cava. Hydatid disease was confirmed
      by a strongly positive serum enzyme-linked immunosorbent assay (ELISA) for
      echinococcus. The patient was treated with high protein intake, dipyramidol and
      captopril; both right lung cysts were resected, followed by the left pulmonary
      cyst 4 weeks later. Hydatid cyst was confirmed histopathologically. He recovered
      well, the serum ELISA for echinococcus became negative, and follow-up urine
      examination and thoracic computerised tomography were normal 6 months after
      surgery, confirming good renal recovery and absence of pulmonary hydatid disease.

PMID- 20822590
TI  - Potential for nosocomial transmission of multidrug-resistant (MDR) tuberculosis
      in a South African tertiary hospital.
AB  - BACKGROUND: Tuberculosis (TB) is a major health problem in the Western Cape, with
      an incidence exceeding 900 per 100 000 people. Nosocomial transmission of TB, and
      particularly drug-resistant TB, is a potential risk that may be undetected. Rapid
      diagnosis and rapid institution of effective anti-TB treatment, combined with
      appropriate infection control measures, are essential to prevent nosocomial
      transmission of TB. To estimate the potential for nosocomial transmission, we
      aimed to determine the in-hospital delays in diagnosis and treatment of patients
      with multidrug-resistant (MDR)-TB at a tertiary care hospital. METHODS: A
      descriptive study, based on retrospective review of patient records and
      laboratory data, including all adult patients (>13 years) where TB culture and
      susceptibility testing confirmed MDR- TB on specimens submitted to Tygerberg
      Hospital's National Health Laboratory Service (NHLS) laboratory in 2007. RESULTS:
      Thirty-one patients with MDR-TB were identified. The median laboratory turnaround
      time (TAT) from collection of specimen to confirmation of MDR-TB was 40 days,
      while the median time from the time of first presentation at Tygerberg Hospital
      to institution of MDR treatment was 44 days. Twenty patients were considered
      infectious during their hospital stay, generating 345 inpatient infectious days.
      CONCLUSIONS: The study suggests that there is an ongoing substantial risk for
      nosocomial transmission of MDR-TB at Tygerberg Hospital. We propose improvements,
      including the use of rapid drug susceptibility testing. The consistent
      application of infection control measures to prevent nosocomial spread of TB,
      including MDR-TB, remains vital.

PMID- 20822591
TI  - The correlation between C-reactive protein and toxic granulation of neutrophils
      in the peripheral blood.
AB  - BACKGROUND: During inflammation, the serum concentrations of granulocyte colony
      stimulating factor (G-CSF), plasma interleukin-6 (IL-6), and C-reactive protein
      (CRP) increase. A positive correlation between CRP and the percentages of
      neutrophils exhibiting toxic granulation during inflammation has been
      demonstrated, and that the fluctuations of CRP and toxic granulation of
      neutrophils were similar. OBJECTIVES: We studied whether grading of toxic
      granulated neutrophils can be used as a surrogate marker for infection or
      inflammation, and also be an easier method than previously described methods.
      MATERIALS AND METHODS: We graded 357 consecutive peripheral blood slides from
      patients on whom a full blood count with differential count and CRP level was
      performed, according to intensity of toxic granulation in the neutrophil
      population, according to a newly proposed grading system. RESULTS: The CRP range
      was between 1 and 530.3 mg/l. The results confirm the association between a rise
      in CRP and progressive intensity of toxic granulation in neutrophils in
      peripheral blood. Kruskal-Wallis equality of populations rank test showed a
      statistically significant difference between the graded categories (p=0.0001).
      The Trend test was also statistically significant (p=0.000). CONCLUSION: The
      proposed system can be applied to patients with inflammatory or infectious
      conditions, where grading of toxic granulation of neutrophils can possibly be
      used as a surrogate marker to assess infection or inflammation and their response
      to treatment. It may be of particular use in cases where traditional infectious
      or inflammatory markers cannot be used, owing to inherent problems associated
      with the respective conditions.

PMID- 20822592
TI  - Anaemia among clinically well under-fives attending a community health centre in
      Venda, Limpopo Province.
AB  - BACKGROUND: Anaemia has been reported to affect 20 - 75% of children in South
      Africa. The range suggests the effects that geography, health, and socio-economic
      status can have on the observed prevalence of anaemia within a specific
      community. Our objective was to investigate the prevalence of anaemia in children
      aged under 5 presenting for well-child examinations at a community health centre
      in Thohoyandou, Limpopo Province. DESIGN: A cross-sectional observational study
      was carried out in June and July 2007. Caregivers participated in a brief
      interview where demographic, health, and nutritional information was collected. A
      blood sample was collected from each child, and haemoglobin levels were assessed
      with a point-of-care haemoglobin testing system. Anaemia was defined as having a
      haemoglobin value <2 standard deviations below age-altitude adjusted normal
      values. RESULTS: Three-quarters (39/52 - 75%) of children were anaemic. Girls
      were significantly more likely to be anaemic than boys (20/20 v. 19/32
      respectively; p=0.001). Anaemic children were significantly less likely to be
      underweight compared with their peers (32/38 v. 5/12 respectively; p=0.007).
      There was no significant association between anaemia and infection with
      Helicobacter pylori (p=0.729), intestinal helminths (p=1.000) or food insecurity
      (p=0.515). CONCLUSION: We found a striking prevalence of anaemia among clinically
      well children <5 years old in Thohoyandou, Limpopo Province. The rates of anaemia
      were higher than those found in previous studies conducted in similar settings in
      South Africa. Future work should focus on aetiologies and interventions.

PMID- 20822593
TI  - Profile and management of patients at a memory clinic.
AB  - Increasing longevity and a growing older population are being accompanied by a
      higher prevalence of dementia and concomitant demand for care. In this
      connection, the University of Cape Town/Groote Schuur Hospital (UCT/GSH) Memory
      Clinic provides a valuable service to patients, families and health
      professionals. High levels of behavioural and psychological symptoms of dementia
      need expert tertiary level assessment and management. Public education on
      dementia, early referral for assessment by primary care health professionals, and
      advanced training of health professionals are needed to encourage early
      recognition and appropriate management. Community-based care services too are
      needed to support caregivers of cognitively impaired older individuals.

PMID- 20822594
TI  - Testicular cancer: Management challenges in an African developing country.
AB  - BACKGROUND: Advances in oncology have greatly improved the prognosis of
      testicular cancer. In developing countries, however, the outcome is still poor.
      PATIENTS AND METHODS: Twenty-four patients managed for testicular cancer at two
      centres (University of Nigeria Teaching Hospital, Enugu, Nigeria, and JAMA
      Urological Clinic, Enugu) between April 1984 and March 2003 were prospectively
      studied. Histopathological data were obtained in all cases. RESULTS: Peak age
      incidence was 20 - 29 years. Testicular swelling was the principal complaint in
      23 patients. The mean interval between onset of symptoms and presentation was 5.3
      months. Two patients (8.3%) presented with stage 1 disease, 7 (29.2%) with stage
      2, 7 (29.2%) with stage 3, and 8 (33.3%) with stage 4. Seventy-five per cent of
      tumours were right-sided, and 25% were left-sided. Treatment consisted of radical
      orchidectomy in all patients and cisplatin-based chemotherapy and radiotherapy in
      some patients. One patient with a tumour in an intra-abdominal testis underwent
      laparotomy. The most common histological types were seminoma and embryonal
      carcinoma. A fifth of the patients died, while half were lost to follow-up. The
      mean follow-up period was 9 months. CONCLUSION: Morbidity and mortality of
      testicular cancer is high in developing countries. Late presentation, poverty,
      paucity of resources and the high cost of newer imaging modalities and treatment
      are major challenges to management. Better health funding and education regarding
      testicular self-examination is essential.

PMID- 20822595
TI  - Snakebite: Admissions at a tertiary health care centre in Maharashtra, India.
AB  - OBJECTIVES: To determine the outcome, seasonal variation, and death pattern of
      snakebite cases admitted at the tertiary health care centre in the last 10 years.
      METHODS: This was a record-based retrospective descriptive study at the Dr
      Shankarrao Chavan Government Medical College and Hospital in Vazirabad, a
      tertiary health care centre in Maharashtra, India. RESULTS: Out of 5 639 admitted
      snakebite cases, 65.24% were male. The 16 - 45-year age group accounted for 84.7%
      of cases; 46% were referred from other health centres, mostly from rural areas;
      55.2% occurred during July to September, which coincided with the rainy season in
      this region; 94.6% of the snakebite patients survived; and 5.4% died. Case
      fatality rates were higher for females (8.78%) and for bites by neurotoxic snakes
      (8.91%). CONCLUSIONS: Snakebite is a common life-threatening emergency in the
      study area. Ready availability and appropriate use of antivenom, early referral
      when required and close monitoring of patients in the hospital will help to
      reduce mortality from snakebites.

PMID- 20822597
TI  - Validation of a dosing regimen for fixed-dose, weight-adjusted, subcutaneous
      unfractionated heparin for the acute treatment of venous thrombo-embolism in a
      population from a resource-constrained environment.
AB  - A study in Canada and New Zealand (Kearon et al.) suggested that fixed-dose
      unmonitored subcutaneous (SC) unfractionated heparin (UFH) is as effective and
      safe as low-molecular-weight heparin (LMWH) for the acute treatment of venous
      thrombo-embolism. While this trial has limitations, it provides evidence to
      support the use of SC UFH in a resource-constrained environment. However, because
      public sector patients with VTE in South Africa often have multiple co
      morbidities and are thinner and younger than those in that study, the local
      validity of the published dosing regimen is unclear.

PMID- 20822598
TI  - Achieving the HIV and AIDS National Strategic Plan: A practical calculator for
      local target setting in district health facilities.
AB  - The South African HIV National Strategic Plan (NSP) aims to provide access to
      appropriate treatment, care and support to 80% of the HIV-infected population by
      2011. By mid-2008, highly active antiretroviral treatment (HAART) was being
      dispensed to about half the HIV-infected population in need. Reaching the NSP
      targets will require full mobilisation of all of South Africa's health
      facilities. While the NSP has broad political and programmatic support from the
      Department of Health and civil society, and managers are able to recite the
      national targets, it has been difficult for these managers to relate the targets
      to their own geographical areas of responsibility. National, regional and
      district targets for HIV care have been set from South Africa's relatively good
      census, modelling and epidemiological data. However, few practical tools are
      available to help clinicians and managers understand their facility's actual
      contribution to the district regional and national NSP targets for each step of
      the HIV care pathway (HIV testing, CD4 testing, HAART referral and initiation).
      The calculation of HAART initiation targets is complicated by the anticipated
      additional demand for treatment that will be generated by a change in the
      recommended CD4-count threshold for initiation of treatment.4 Accordingly, we
      provide a data-based tool that is readily available, and that district and
      facility managers can use to calculate their annual steady-state HIV testing, CD4
      testing and HAART initiation requirements. These calculated values can be used
      for local and regional planning and to assess and improve current performance at
      facility level.

PMID- 20822599
TI  - Emergency centres lack defibrillator knowledge.

PMID- 20822600
TI  - Surviving in the public sector.

PMID- 20822601
TI  - The scramble for influenza vaccine in 2010.

PMID- 20822606
TI  - Delusions: What truth to believe?

PMID- 20822608
TI  - IVH - the rise (and fall) of the surfactant dose?

PMID- 20822609
TI  - Approval of chronic medication - Discovery Health hits new lows.

PMID- 20822610
TI  - 'No deals' for unlucky few strikers - HPCSA.

PMID- 20822611
TI  - 'Want private sector help? Make state health care managers accountable'.

PMID- 20822612
TI  - Mostly warnings for welfare staff who stole/squandered R70 million.

PMID- 20822613
TI  - Multiple organ failure - death of consumer protection?
AB  - The enormously profitable complementary medicines, dietary supplements and
      traditional medicines markets are largely unregulated internationally and South
      Africa. Attempts to ensure that consumers are not exposed to harmful or
      ineffective products have met with varying success around the world.

PMID- 20822614
TI  - Requiem for Babinski.

PMID- 20822615
TI  - Lionel Shelsley (LS) Smith (10 July 1922 - 29 November 2009).

PMID- 20822616
TI  - The four pillars of rheumatic heart disease control.

PMID- 20822617
TI  - A paradoxical reduction in upper genital tract infection despite the massive HIV
      epidemic.

PMID- 20822618
TI  - Pleuro-pulmonary disease in central South Africa: A thoracic surgical deficiency.
AB  - We wished to estimate the performance gap between thoracic surgical service
      provision and the burden of thoracic surgical disease in central South Africa
      (SA). We compared burden of disease data to the number of thoracic operations
      performed for inflammatory pleuro-pulmonary disease and primary lung cancer. The
      performance gap was estimated to be a factor of 1:20 for lung cancer and 1:10 for
      thoracic surgery as a whole. The extent of under-provision of thoracic surgical
      services in central SA demonstrates that urgent major healthcare system reforms
      are required at all levels to address the significant performance gap between
      service provision by thoracic surgery and the burden of disease in central SA.

PMID- 20822619
TI  - Haiti: The South African perspective.
AB  - BACKGROUND AND PROBLEM STATEMENT: The South African response to the Haitian
      earthquake consisted of two independent non-government organisations (NGOs)
      working separately with minimal contact. Both teams experienced problems during
      the deployment, mainly owing to not following the International Search and Rescue
      Advisory Group (INSARAG) guidelines. CRITICAL AREAS IDENTIFIED: To improve future
      South African disaster responses, three functional deployment categories were
      identified: urban search and rescue, triage and initial stabilisation, and
      definitive care. To best achieve this, four critical components need to be taken
      into account: rapid deployment, intelligence from the site, government
      facilitation, and working under the auspices of recognised organisations such as
      the United Nations and the World Health Organization. CONCLUSION: The proposed
      way forward for South African medical teams responding to disasters is to be
      unified under a leading academic body, to have an up-to-date volunteer database,
      and for volunteers to be current with the international search and rescue course
      currently being developed by the Medical Working Group of INSARAG. An additional
      consideration is that South African rescue and relief personnel have a primary
      responsibility to the citizens of South Africa, then the Southern African
      Development Community region, then the rest of the African continent and finally
      further afield. The commitment of government, private and military health
      services as well as NGOs is paramount for a unified response.

PMID- 20822620
TI  - Canada's health care system: A relevant approach for South Africa?
AB  - BACKGROUND: While countries such as the USA, South Africa and China debate health
      reforms to improve access to care while rationalising costs, Canada's health care
      system has emerged as a notable option. In the USA, meaningful discussion of the
      advantages and disadvantages of the Canadian system has been thwarted by
      ideological mudslinging on the part of large insurance companies seeking to
      preserve their ultra-profitable turf and backed by conservative political forces
      stirring up old fears of 'socialised medicine'. These distractions have relegated
      the possibility of a 'public option' to the legislative dustbin, leaving tens of
      millions of people to face uninsurance, under-insurance, bankruptcy and
      unnecessary death and suffering, even after passage of the Obama health plan.
      While South Africa appears to experience similar legislative paralysis, there
      remains room for reasoned health reform debate to address issues of equity,
      access, and financing. OBJECTIVE: Our aim is to contribute to the debate from a
      Canadian perspective, setting out the basic principles of Medicare (Canada's
      health care system), reviewing its advantages and challenges, clarifying
      misunderstandings, and exploring its relevance to South Africa. We periodically
      refer to the USA because of the similarities to the South African situation,
      including its health care system, which mirrors South Africa's current position
      if left unchanged. CONCLUSION: While Medicare is neither flawless nor a model
      worthy of wholesale imitation, we contend that open discussion of Canada's
      experience is a useful component in South Africa's current policy and political
      efforts.

PMID- 20822621
TI  - Does South Africa need a national clinical trials support unit?
AB  - BACKGROUND: No national South African institution provides a coherent suite of
      support, available skills and training for clinicians wishing to conduct
      randomised controlled trials (RCTs) in the public sector. We report on a study to
      assess the need for establishing a national South African Clinical Trials Support
      Unit. OBJECTIVES: To determine the need for additional training and support for
      conduct of RCTs within South African institutions; identify challenges facing
      institutions conducting RCTs; and provide recommendations for enhancing trial
      conduct within South African public institutions. DESIGN: Key informant
      interviews of senior decision-makers at institutions with a stake in the South
      African public sector clinical trials research environment. RESULTS: Trial
      conduct in South Africa faces many challenges, including lack of dedicated
      funding, the burden on clinical load, and lengthy approval processes. Strengths
      include the high burden of disease and the prevalence of treatment-naive
      patients. Participants expressed a significant need for a national initiative to
      support and enhance the conduct of public sector RCTs. Research methods training
      and statistical support were viewed as key. There was a broad range of views
      regarding the structure and focus of such an initiative, but there was agreement
      that the national government should provide specific funding for this purpose.
      CONCLUSIONS: Stakeholders generally support the establishment of a national
      clinical trials support initiative. Consideration must be given to the
      sustainability of such an initiative, in terms of funding, staffing, expected
      research outputs and permanence of location.

PMID- 20822622
TI  - Can fireworks-related injuries to children during festivities be prevented?
AB  - OBJECTIVE: To determine the epidemiological features and outcome of fireworks
      related injuries among children 0 - 13 years old. DESIGN: A retrospective study
      from the trauma registry of a children's hospital from 2001 - 2009. RESULTS:
      Fifty-five children were treated for injuries from fireworks. The mean age was
      8.8 years, 78% were boys, and the largest age group was 5 - 9 years old.
      Firecrackers accounted for 95% of the injuries; the most commonly injured body
      sites were hands (44%), eyes (42%) and face (31%); 47% of the patients had more
      than one injury. The most common injury type was burns (67%); 25 children were
      admitted, mostly to the burns and ophthalmology units. The mean length of
      hospital stay was 3.5 days. Surgical intervention was required in 38% of the
      patients. Most of the fireworks accidents occurred in or around the patients'
      homes. There were more fireworks-related injuries around Guy Fawkes Day (85%)
      than New Year's Eve (9%). CONCLUSION: Consumer fireworks cause serious but
      preventable injuries to children, either as users or bystanders. Children and
      their families should be encouraged to enjoy pyrotechnical displays conducted by
      professionals at designated areas. All fireworks for individual private use
      should either be supervised by an adult or banned. Current legislation should be
      more strictly enforced, especially the sale to under-age children.

PMID- 20822623
TI  - Microbiology of acute complicated bacterial sinusitis at the University of the
      Witwatersrand.
AB  - DESIGN: A retrospective chart review study at two referral hospitals identified
      226 consecutive surgical patients with acute complicated sinusitis. SUBJECTS: One
      hundred and fifty-nine male and 67 female patients, with a mean age of 16.5
      (standard deviation 0.7) years, underwent external fronto-ethmoidectomy with
      maxillary sinus washout and 13 had a concurrent craniotomy. RESULTS: A total of
      233 micro-organisms were isolated from 163 patients(72.1%), and 63 (27.9%) were
      culture-negative. Positive isolates included Streptococcus milleri (18.5%),
      Staphylococcus aureus (12.4%), beta-haemolytic streptococci (10.8%), coagulase
      negative staphylococci (8.6%), Haemophilus influenzae (8.6%) and the anaerobes,
      Peptostreptococcus (6.4%) and Prevotella (4.7%) species. The prevalences of S.
      pneumoniae (2.6%), methicillin-resistant S. aureus (MRSA) (1.3%) and Moraxella
      catarrhalis (0.4%) were low. Polymicrobial disease was present in 56 patients
      (34.4%). There was a significant difference between the two hospitals in the
      prevalences of some bacteria (p<0.05). Antibiotic resistance was highest towards
      the penicillins (64.3%) and cephalosporins (12.5%). Effective empiric treatment
      was achieved with metronidazole and a choice of amoxicillin-clavulanate or
      ampicillin plus cloxacillin or penicillin plus chloramphenicol. CONCLUSION: The
      polymicrobial nature and severity of complicated sinusitis warrants a de
      escalation approach to antimicrobial therapy. The combination of beta-lactamase
      resistant penicillins and metronidazole is a reasonable choice for initial
      empiric antibacterial therapy. Selection of drugs for empirical antibiotic
      therapy in patients with acute complicated sinusitis should be supported by
      knowledge of the local prevalence and antimicrobial susceptibilities of bacteria
      isolated from patients.

PMID- 20822624
TI  - Balantidium coli-induced pulmonary haemorrhage with iron deficiency.
AB  - BACKGROUND: Balantidium coli, a ciliated protozoan parasite that infects primates
      and pigs, and is the largest protozoan to infect humans, is a well-known cause of
      diarrhoea and dysentery in humans. Extra-intestinal disease is uncommon, however.
      OBJECTIVE: We describe a case of lung involvement, with severe pulmonary
      haemorrhage resulting in iron deficiency anaemia and respiratory failure, of a 20
      year-old, immune-competent man. RESULTS: Diagnosis was made by bronchial biopsy
      and lavage, which showed numerous trophozoites compatible with B. coli with a
      background of acute inflammatory cells. The origin of infection was not clear,
      but inhalation of pig manure was postulated as there was no history of intestinal
      disease. The patient was treated with oxytetracyline and metronidazole, kept in
      an ICU, improved within 48 hours, and was discharged within 4 days. CONCLUSION:
      B. coli infection should be considered as part of the differential diagnosis of
      pulmonary haemorrhage.

PMID- 20822625
TI  - Haitian reflections.
AB  - Natural disasters and acts of terrorism demonstrate a similar critical need for
      national preparedness. As one of a team of volunteers with a local South African
      NGO who recently went on a medical mission, I would like to share glimpses of our
      experience and reflect on the mistakes - and also to state the obvious: that we
      do not learn from our mistakes. A simple literature search has shown that the
      same mistakes happen repeatedly. 'Humanitarian disasters occur with frightening
      regularity, yet international responses remain fragmented, with organizations and
      responders being forced to "reinvent the wheel" with every new event'. This is
      the result of an obvious lack of preparedness.

PMID- 20822628
TI  - South Africa's first century.

PMID- 20822630
TI  - Clinical haematology training in South Africa.

PMID- 20822631
TI  - Traditional circumcision--the unkindest cut of all.

PMID- 20822632
TI  - CRP and toxic granulation.

PMID- 20822633
TI  - Vuvuzelas: Ex Africa semper aliquid novis--again?

PMID- 20822634
TI  - The UCT Department of Medicine at 90 years: continuity and change.

PMID- 20822635
TI  - Haiti tragedy shakes up SA's emergency response planning.

PMID- 20822636
TI  - Silver 'porn bullet' for information technology industry?

PMID- 20822637
TI  - Still a long wait for approved HIV-protective gel.

PMID- 20822638
TI  - Bullish new medical measures to give more pilots wings.

PMID- 20822639
TI  - Prolonged deferral of antiretroviral therapy in the SAPIT trial: did we need a
      clinical trial to tell us that this would increase mortality?

PMID- 20822640
TI  - Establishing liability for harm caused to patients in a resource-deficient
      environment.

PMID- 20822643
TI  - Intimate partner violence: are we ready for action?

PMID- 20822644
TI  - Is 'planning' missing from our family planning services?

PMID- 20822645
TI  - New fly species causing human myiasis identified in Eastern Cape, South Africa.

PMID- 20822647
TI  - Guns and gender-based violence in South Africa.
AB  - BACKGROUND: The criminal use of firearms in South Africa is widespread and a
      major factor in the country having the third-highest homicide rate in the world.
      Violence is a common feature of South African society. A firearm in the home is a
      risk factor in intimate partner violence, but this has not been readily
      demonstrated in South Africa because of a lack of data. METHODS: We drew on
      several South African studies including national homicide studies, intimate
      partner studies, studies with male participants and studies from the justice
      sector, to discuss the role of gun ownership on gender-based violence.
      CONCLUSION: Guns play a significant role in violence against women in South
      Africa, most notably in the killing of intimate partners. Although the overall
      homicide data suggest that death by shooting is decreasing, data for intimate
      partner violence are not readily available. We have no idea if the overall
      decrease in gunshot homicides applies to women in relationships, and therefore
      gun control should remain high on the legislative agenda.

PMID- 20822646
TI  - Intimate partner violence, health behaviours, and chronic physical illness among
      South African women.
AB  - OBJECTIVES: An association between intimate partner violence and adverse physical
      health outcomes and health-risk behaviours among women has been established, most
      scientific research having been conducted in the USA and other developed
      countries. There have been few studies in developing countries, including South
      Africa, which has one of the highest rates of intimate partner violence in the
      world. We therefore sought to study the association between physical intimate
      partner violence and physical health outcomes and behaviours among South African
      women. METHODS: Using data from the cross-sectional, nationally representative
      South Africa Stress and Health Study, we assessed exposure to intimate partner
      violence, health-risk behaviours, health-seeking behaviours and chronic physical
      illness among a sample of 1 229 married and cohabiting women. RESULTS: The
      prevalence of reported violence was 31%. This correlated with several health-risk
      behaviours (smoking, alcohol consumption, and use of non-medical sedatives,
      analgesics and cannabis) and health-seeking behaviours (recent visits to a
      medical doctor or healer). Intimate partner violence was not significantly
      associated with chronic physical illness, although rates of headache, heart
      attack and high blood pressure reached near-significance. CONCLUSIONS: Partner
      violence against women is a significant public health problem in South Africa,
      associated with health-risk behaviours and increased use of medical services.
      Public health programmes should incorporate interventions to mitigate the impact
      of violence on victims and reduce the risk of negative behavioural outcomes.
      Further investigation of the pathways between violence exposure and health
      behaviours is needed to inform the design of such programming.

PMID- 20822648
TI  - Towards universal ARV access: achievements and challenges in Free State Province,
      South Africa.
AB  - OBJECTIVE: To study the progress and challenges with regard to universal
      antiretroviral (ARV) access in Free State Province, South Africa. METHODS: Data
      from the first 4 years of the public sector ARV roll-out and selected health
      system indicators were used. Data were collected from the public sector ARV
      database in Free State Province for new patients on ARVs, average waiting times
      and median CD4 counts at the start of treatment. Information on staff training,
      vacancy rates and funding allocations for the ARV roll-out was obtained from
      official government reports. Projections were made of expected new ARV enrolments
      for 2008 and 2009 and compared with goals set by the National Strategic Plan
      (NSP) to achieve universal access to ARVs by 2011. RESULTS: New ARV enrolments
      increased annually to 25% of the estimated need by the end of 2007. Average
      waiting times to enrolment decreased from 5.82 months to 3.24 months. Median CD4
      counts at enrolment increased from 89 to 124 cells/mm3. There is a staff vacancy
      rate of 38% in the ARV programme and an inadequate increase in budget
      allocations. CONCLUSION: The current vertical model of ARV therapy delivery is
      unlikely to raise the number of new enrolments sufficiently to achieve the goals
      of universal access by 2011 as envisaged by the NSP. The Free State is
      implementing a project (STRETCH trial) to broaden the ARV roll-out in an attempt
      to increase access to ARVs.

PMID- 20822649
TI  - Epidemiology of conventional cardiovascular risk factors among hypertensive
      subjects with normal and impaired fasting glucose.
AB  - BACKGROUND: Impaired fasting or glucose tolerance and/or diabetes can occur with
      hypertension, which theoretically predicts a worse cardiovascular risk profile,
      and consequently requires intensive cardiovascular risk management. OBJECTIVES:
      To characterise the frequency of the occurrence of conventional cardiovascular
      risk factors among hypertensive subjects with impaired fasting blood glucose.
      METHODS: We studied 120 hypertensive subjects and 80 age- and sex-matched
      normotensive controls. Relevant history, clinical examination, laboratory and
      other tests were undertaken. Body mass index was determined. Informed consent was
      obtained from all participants, and ethical approval was obtained. RESULTS: There
      was no statistically significant difference between the age and gender of the
      hypertensive subjects and the controls (55.1+/-10.83 v. 54.7+/-10.89 years,
      p=0.76). The serum fasting lipids were higher, but not statistically
      significantly, among the hypertensives than the controls (triglycerides 1.23+/
      0.50 v. 1.22+/-0.48, p=0.900; total cholesterol 4.51+/-1.52 v. 4.38+/-0.84,
      p=0.842; LDL 2.51+/-1.41 v. 2.4+/-0.63, p=0.811, respectively). The prevalence of
      impaired glucose tolerance among newly presenting hypertensive subjects was
      30.0%. Hypertriglyceridaemia (38.9% v. 6.0%, p=0.038), hypo-HDL cholesterolaemia
      (52.7% v. 31.0%, p=0.028) and visceral obesity (52.8% v. 27.4%, p=0.036) were
      statistically more prevalent among hypertensive subjects with impaired glucose
      tolerance than among those with normal glucose tolerance. CONCLUSION: The
      prevalence of impaired glucose tolerance among newly presenting hypertensive
      subject is very high, and they have more clusters of cardiovascular risks than
      those without impaired glucose tolerance. The former therefore need intensive
      cardiovascular assessment and appropriate preventive and treatment modalities.
      Glucose parameters of newly presenting hypertensive subjects must be determined
      to evaluate their cardiovascular risk profile.

PMID- 20822650
TI  - Dual time-point FDG PET-CT for differentiating benign from malignant solitary
      pulmonary nodules in a TB endemic area.
AB  - OBJECTIVE: Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is an
      accurate non-invasive imaging test for differentiating benign from malignant
      solitary pulmonary nodules (SPNs). We aimed to assess its diagnostic accuracy for
      differentiating benign from malignant SPNs in a tuberculosis (TB)-endemic area.
      METHODS: Thirty patients, 22 men and 8 women, mean age 60 years, underwent dual
      time point FDG-PET/computed tomography (CT) imaging, followed by histological
      examination of the SPN. Maximum standard uptake values (SUVmax) with the greatest
      uptake in the lesion were calculated for two time points (SUV1 and SUV2), and the
      percentage change over time per lesion was calculated (%DSUV). Routine
      histological findings served as the gold standard. RESULTS: Histological
      examination showed that 14 lesions were malignant and 16 benign, 12 of which were
      TB. SUVmax for benign and malignant lesions were 11.02 (standard deviation (SD)
      6.6) v. 10.86 (SD 8.9); however, when tuberculomas were excluded from the
      analysis, a significant difference in mean SUV1max values between benign and
      malignant lesions was observed (p=0.0059). Using an SUVmax cut-off value of 2.5,
      a sensitivity of 85.7% and a specificity of 25% was obtained. Omitting the TB
      patients from analysis resulted in a sensitivity of 85.7% and a specificity of
      100%. Mean %DSUV of benign lesions did not differ significantly from mean %DSUV
      of malignant lesions (17.1% (SD 16.3%) v. 19.4% (SD 23.7%)). Using a cut-off of
      %DSUV>10% as indicative of malignancy, a sensitivity of 85.7% and a specificity
      of 50% was obtained. Omitting the TB patients from the analysis yielded a
      sensitivity of 85.7% and a specificity of 75%. CONCLUSION: Our findings suggest
      that FDG-PET cannot distinguish malignancy from tuberculoma and therefore cannot
      reliably be used to reduce futile biopsy/thoracotomy.

PMID- 20822651
TI  - Clinical predictors of low CD4 count among HIV infected pulmonary tuberculosis
      clients: a health facility-based survey.
AB  - OBJECTIVES: The study aimed to determine the clinical and laboratory predictors
      of a low CD4+ cell count (<200 cells/microl) in HIV-infected patients with
      pulmonary tuberculosis (PTB). DESIGN AND SETTING: A prospective cohort study on
      HIV-positive patients with smear-positive PTB attending an outpatient clinic in
      Zimbabwe. PARTICIPANTS: Consecutively consenting HIV-positive adults, aged 18
      years and over, who had positive sputum smears for acid-fast bacilli and were
      naive to both antituberculosis drugs and ART. INTERVENTIONS: Baseline CD4+ cell
      count, full blood count, functional status using the Karnofsky Performance Status
      (KPS) score and body mass index (BMI, kg/m2) were determined for all
      participants. Univariate and multiple logistic regression analyses of the data
      were done. RESULTS: Of the 97 participants recruited, 59 (61%) were females. The
      overall mean age was 34 years (standard deviation (SD) 8). The median CD4+ cell
      count was 104.5 cells/microl (intraquartile range (IQR) 41-213 cells/microl).
      Patients with pleuritic chest pain were less likely to have a low CD4+ cell count
      than patients who did not (odds ratio (OR) 0.2; confidence interval (CI) 0.03
      0.8). The following were statistically significant predictors of a CD4+ cell
      count of <200 cells /microl: BMI<18 kg/m2 (OR 3.8; CI 1.2-12), KPS<54.4 (OR 3; CI
      1.1-12) and haemoglobin concentration<8 g/dl (OR 13; CI 1.8 - 533). CONCLUSIONS:
      HIV-infected sputum-positive PTB patients presenting with a BMI<18, KPS<54.4% and
      haemoglobin concentration<8 g/dl should have early initiation of ART since they
      are more likely to have a low CD4+ cell count, whereas those presenting with
      pleuritic pain are less likely to have a low CD4+ cell count.

PMID- 20822654
TI  - Validated binary high-performance thin-layer chromatographic fingerprints of
      polyphenolics for distinguishing different Salvia species.
AB  - Salvia (sage) is the largest plant genus in the family Lamiaceae, embracing ca.
      900 species. There is a growing interest in investigating chemical contents of
      different Salvia species, as some of them have been reported to exhibit a wide
      spectrum of biological activity. In this paper, conjugated (i.e., binary)
      chromatographic fingerprints have been introduced for the twenty Salvia species
      that are grown and cultivated in Poland. Apart from videoscans traditionally used
      for a comparison of the high-performance thin-layer chromatography fingerprints,
      digital scanning profiles and images obtained with use of the image processing
      program have also been employed. It is the first time that binary chromatographic
      fingerprints are used for the investigation of chemical contents of the Salvia
      species. The proposed procedure is rapid when compared with the similar ones
      presented in the literature, and moreover, it is easy to handle. The proposed
      method offers a possibility to discern the investigated species. It can be
      applied not only for chemotaxonomic purposes but also for finding new plant
      species that can be used as medical herbs (as it has been proposed, with S.
      triloba having a similar profile to S. officinalis). Validation of the method
      reveals that it is specific, reproducible, precise, and robust.

PMID- 20822655
TI  - Fingerprint development for Ginkgo biloba extracts by pressurized capillary
      electrochromatography: comparison of column types.
AB  - A pressurized capillary electrochromatographic (pCEC) fingerprint of Ginkgo
      biloba leaf extract was developed on three different types of capillary columns.
      A commercial column packed with 3-microm particles and an in-house column packed
      with 5-microm particles were investigated for their performance. Additionally, a
      monolithic column was included in the fingerprint study as a potential
      alternative to the conventional packed columns. The effects of experimental
      parameters, such as the composition of the mobile phase, the concentration and pH
      of the buffer, and the applied voltage, were studied. Binary mobile phases
      consisting of acetonitrile and a 5 mM sodium dihydrogen phosphate electrolyte at
      pH 2.8 were used in gradient elution mode with an applied voltage of 5 kV. Under
      optimal gradient conditions, at least 45 peaks were observed within 60 min on the
      commercial packed column, whereas only about 20 peaks were separated on the
      methacrylate-based monolithic and the in-house packed columns. The commercial
      column thus clearly outperforms the two other. However, the properties of the
      monolithic stationary phase still might be adapted (i.e., by changing the
      polymerization-mixture composition, the porosity, and thus the selectivity of the
      phase might be changed), which could lead to an improved efficiency.

PMID- 20822656
TI  - Determination of capsidiol in tobacco cells culture by HPLC.
AB  - Capsidiol is a bicyclic sesquiterpene, which accumulates extracellularly in
      plants, and has been isolated from many types of Solanaceae. It acts as a
      phytoalexin produced by Nicotiana tabacum in response to pathogens. Capsidiol has
      antifungal activity and is formed first in tobacco and pepper plants after
      infestation. The amount of capsidiol in tobacco cell suspension culture has been
      previously determined by solid-phase extraction and organic solvent extraction
      with thin-layer chromatography or gas chromatography analysis. A high-performance
      liquid chromatography method with UV detection at 210 nm on a C(8) column
      utilizing both extraction methods was developed to analyze capsidiol in
      suspension cell culture. The HPLC method was linear in the concentration range of
      0.1-2.0 mg/L. The lower limit of quantitation was 0.1 mg/L. Organic solvent
      extraction and solid-phase extraction methods were compared. Both methods are
      generally similar in their overall efficiency (82% and 75%, respectively), but
      eliminations of interfering compounds are different. The relative standard
      deviation across five extractions of known amounts of capsidiol from plant sample
      was less than 5.1%. The relative standard deviation across five elicitations of
      cell cultures was less than 5.9%. Gas chromatography-mass spectrometry and liquid
      chromatography-mass spectrometry analysis of capsidiol was performed, and
      corresponding mass spectra are presented.

PMID- 20822657
TI  - HPLC-MS analysis of ethanol extract of Corydalis yanhusuo and simultaneous
      determination of eight protoberberine quaternary alkaloids by HPLC-DAD.
AB  - An accurate and simple analysis method by high-performance liquid chromatography
      (HPLC)-electrospray tandem mass spectrometry (ESI-MS-MS) for the ethanol extract
      of Corydalis yanhusuo was established in this study. In this method, a C(18)
      column was used, and the mobile phase was water (0.2% acetic acid, 0.1%
      triethylamine, v/v)-acetonitrile (24:76, v/v). Under the optimal analysis
      conditions established in this study, eight protoberberine quaternary alkaloids
      in the ethanol extract of Corydalis yanhusuo were well separated and identified,
      respectively. Eight regression equations showed a good linear relationship
      between the peak area of each marker and concentration (r = 0.9990-0.9995). The
      various other aspects of analysis (i.e., peak purity, precision, recovery, and
      repeatability) were also validated. For the eight components, the recoveries were
      found to be 98.9%, 99.2%, 105.0%, 97.7%, 101.4%, 98.6%, 98.5%, and 98.7%,
      respectively. The limits of detection were 14.6, 42.5, 22.4, 17.9, 25.4, 10.0,
      18.7, 3.9 ng/mL, respectively, and the limits of quantitation were 48.6, 141.7,
      74.6, 59.6, 84.8, 33.2, 62.3, and 12.9 ng/mL, respectively. The developed method
      is useful for the simultaneous determination of these alkaloids in a large number
      of ethanol extracts of Corydalis yanhusuo.

PMID- 20822658
TI  - Determination of a pyranocoumarin and three carbazole compounds in Clausena
      excavata by RP-HPLC.
AB  - Clausenidin, O-methylmukonal, 3-formyl-2,7-dimethoxycarbazole, and clauszoline-J,
      isolated from the rhizomes and roots of Clausena excavata, exhibit anti-HIV-1
      activity in a syncytial assay with EC(50) values of 5.3, 12.0, 29.1, and 34.2
      microM, respectively. Due to the highly active anti-HIV-1 property, quantitative
      analysis of four compounds are investigated. The direct analysis of these four
      compounds in the crude extracts of the combined rhizomes and roots of Clausena
      excavata from ten various sources in Thailand by high-performance liquid
      chromatography is accomplished. Chromatographic separation is achieved on a C(18)
      column, and the mobile phase is a mixture of methanol and distilled water in a
      mode of isocratic or gradient elution detected at 254 nm at a flow rate of 0.6
      mL/min for clausenidin, at 274 nm at a flow rate of 0.6 mL/min for O
      methylmukonal, at 298 nm at a flow rate of 0.4 mL/min for 3-formyl-2,7
      dimethoxycarbazole, and at 242 nm at a flow rate of 0.4 mL/min for clauszoline-J.
      This is the first quantitative analysis of these four anti-HIV-1 compounds from
      the crude extract without prior isolation and purification steps.

PMID- 20822659
TI  - Determination of thiamphenicol in honey by dispersive liquid-liquid
      microextraction with high-performance liquid chromatography.
AB  - Dispersive liquid-liquid microextraction (DLLME) coupled with high-performance
      liquid chromatography-variable wavelength detector (HPLC-VWD) was developed for
      extraction and determination of thiamphenicol (THA) in honey. A mixture of
      extraction solvent (30 microL 1,1,2,2-tetrachloroethane) and dispersive solvent
      (1.0 mL of acetonitrile) was rapidly injected into 5.00 mL sample solution for
      the formation of cloudy solution. The analyte in the sample was extracted into
      the fine droplets of C(2)H(2)Cl(4). After extraction, phase separation was
      performed by centrifugation, and the enriched analyte in the sedimented phase was
      determined by HPLC-VWD. Some important parameters, such as the kind and volume of
      extraction solvent and dispersive solvent, extraction time, sample solution pH,
      sample volume, and salt effect, were investigated and optimized. Under the
      optimum extraction condition, the method yielded a linear calibration curve in
      the concentration range from 3 to 2000 microg/kg for target analyte. The
      enrichment factors for THA was 87.9, and the limit of detection (S/N = 3) was 0.1
      microg/kg. The relative standard deviation for the extraction of 10 microg/kg of
      THA was 6.2% (n = 6). The main advantages of DLLME-HPLC method are simplicity of
      operation, rapidity, low cost, high enrichment factor, high recovery, good
      repeatability, and extraction solvent volume at the microL level. Honey samples
      were successfully analyzed using the proposed method.

PMID- 20822660
TI  - Antioxidant assay-guided purification and LC determination of ellagic acid in
      pomegranate peel.
AB  - On the basis of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay
      guided purification, ellagic acid was isolated from the methanol extract of
      pomegranate fruit peel by liquid-liquid extraction and chromatographic
      techniques. A reversed-phase high-performance liquid chromatography was described
      for determination of ellagic acid in pomegranate fruit peel extract. The method
      involved the use of a TSK-gel ODS-80Tm column with a mixture of 2% aqueous acetic
      acid and methanol (gradient elution mode: 0-15 min, 40-60% v/v methanol and 15-20
      min, 60% v/v methanol) as the mobile phase and detection at 254 nm. The
      parameters of linearity, repeatability, reproducibility, accuracy, and
      specificity of the method were evaluated. The recovery of the method was 98.5%
      and linearity (r(2) > 0.9995) was obtained for ellagic acid. A high degree of
      specificity as well as repeatability and reproducibility (relative standard
      deviation values less than 5%) were also achieved. The limits of detection and
      quantification were 1.00 and 2.50 microg/mL, respectively. The solvent for
      extraction of ellagic acid from pomegranate fruit peel was examined in order to
      maximize the ellagic acid content of the extract. A solution of 10% v/v water in
      methanol was capable of increasing the ellagic acid content in the extract up to
      7.66% w/w. The ellagic acid content and antioxidant activity of the ethyl acetate
      fraction separated from the crude extract using water and ethyl acetate partition
      was higher than that of the crude extract.

PMID- 20822661
TI  - A sensitive HPLC-ESI-MS-MS method for the determination of cotinine in urine.
AB  - A simple, sensitive, selective, and reproducible method based on high-performance
      liquid chromatography-electrospray ionization-tandem mass spectrometry was
      developed for the determination of nicotine and its major metabolite cotinine in
      human urine. The internal standard (acetaminophen) was separated from cotinine on
      a Hypersil Gold C(18) column with retention times of 9.3 and 13.0 min,
      respectively. The mobile phase consisted of a mixture of 10 mM acetate buffer (pH
      5.4) and methanol (45:55, v/v), running through the column at a flow rate of 0.6
      mL/min. The chromatographic analysis was operated at 25 degrees C. Sample
      preparation was prepared by liquid-liquid extraction with a mixture of methyl-t
      butyl ether in dichloromethane (1:1, v/v). The precision of the method based on
      within-day repeatability and reproducibility (day-to-day variation) was below 15%
      (% coefficient of variation). Good accuracy was observed for both the intra-day
      or inter-day assays. Limit of quantification was accepted as 0.02 ng using 100 mL
      samples. The mean recoveries for cotinine and the internal standard were greater
      than 90%. The method has been applied to the investigation of a 2-h urinary
      excretion of cotinine in 154 healthy non-smoking Thai volunteers (aged 18-45
      years) following the administration of a half-piece (2 mg) of nicotine gum.

PMID- 20822663
TI  - Thin-layer chromatographic specification and separation of Cu(1+), Cu(2+),
      Ni(2+), and Co(2+) cations.
AB  - The M(PyDTC)(2) (M: Cu, Co, or Ni) and CuPyDTC complexes, prepared by reactions
      of ammonium pyrrolidinedithiocarbamate with metal nitrates, are examined for
      qualitative analysis, speciation, and mutual separation using thin-layer
      chromatography systems. These complexes and their mixtures are spotted to the
      activated and non-activated thin layers of silica gel 60GF(254) (Si-60GF(254))
      with a 250-microm thickness. Toluene-dichloromethane mixtures (4:1, 1:1, 1:4 v/v)
      are used as mobile phases for running of the complexes. All of these
      chromatographic systems are successfully used for speciation of Cu(2+) and Cu(1+)
      cations. The best analytical separation for the qualitative analysis of
      corresponding metal cations and mutual separation of components in M(PyDTC)(2)
      and CuPyDTC complexes are obtained when using pure toluene-dichloromethane (1:1
      v/v) on the activated layer. This study shows that it is possible to
      qualitatively analyze and satisfactorily separate a mixture of Cu(1+), Cu(2+),
      Ni(2+), and Co(2+) cations on cited chromatographic systems. These results may be
      also said for the adaptability or validity on column chromatography.

PMID- 20822662
TI  - Catalytically-promoted analyte derivatization inside a gas chromatographic inlet.
AB  - Reported here is a preliminary assessment of the feasibility of catalyzing on
      line derivatization reactions inside the inlet (i.e., the injection port) of a
      gas chromatograph (GC) with solid heterogeneous catalysts. The experiments
      described here entail the installation of candidate catalysts inside the GC inlet
      liner and the subsequent injection of analyte/reagent mixtures onto the catalyst
      beds. Two catalysts are identified, each of which clearly catalyzes one of the
      chosen model derivatization reactions in the inlet of a GC. This result supports
      our hypothesis that on-line derivatizations can, in principle, be reproducibly
      catalyzed inside the GC inlet by solid heterogeneous catalysts and that the
      presence of such catalysts in the inlet do not necessarily cause a serious loss
      of instrument performance or chromatographic efficiency.

PMID- 20822664
TI  - Application of moment analysis to mass transfer kinetics of reversed-phase liquid
      chromatography: part 1. Experimental investigation of measurement of the third
      central moment.
AB  - The first three statistical moments of the eluted band profiles from reversed
      phase liquid chromatographic columns were attempted to be measured and analyzed
      in this work. And in this first part, the effect of the experimental conditions
      on the measurement accuracy of the third central moment is investigated. The
      optimized experimental condition is determined under which the measurement
      accuracy of the third central moment is much improved. Further analysis of the
      measurement result of the third central moment (micro(3)) shows that the linear
      correlation exists between micro(3)u(0)(4) and the flow velocity (u(0)).

PMID- 20822665
TI  - A single reversed-phase UPLC method for quantification of levofloxacin in aqueous
      humour and pharmaceutical dosage forms.
AB  - An attempt was made to develop a single, rapid, specific, and sensitive gradient
      reversed-phase ultra-performance liquid chromatographic method for quantitative
      analysis of levofloxacin. The single method thus developed is applied for the
      quantification of levofloxacin both in aqueous humour as well as pharmaceutical
      dosage forms (i.e., tablets and eye drops). The newly developed method is
      applicable for pharmacokinetic studies of eye formulations. The chromatographic
      separation of levofloxacin was achieved on a Waters Acquity HSS T-3 column (100 x
      2.1 mm, 1.8 microm) within a short run-time of 5 min. The method was validated
      according to the ICH guidelines with respect to system suitability, linearity,
      limit of quantitation and detection, precision, accuracy, robustness, and
      specificity. Forced degradation studies were also performed in levofloxacin bulk
      drug samples to demonstrate the stability-indicating power of the developed ultra
      performance liquid chromatography method. The developed method was then
      successfully applied for the ocular pharmacokinetic study of levofloxacin eye
      formulations and assay of levofloxacin pharmaceutical dosage form.

PMID- 20822666
TI  - Quantification of rimonabant (SR 141716A) in monkey plasma using HPLC with UV
      detection.
AB  - Using an isocratic high-performance liquid chromatography (HPLC) system and UV
      detection, a simple and precise analytical procedure was developed to quantify
      levels of the CB(1) receptor antagonist rimonabant in the plasma of rhesus
      monkeys. Rimonabant was extracted from plasma samples into 5% isopropanol in
      hexane. After separation, the isopropanol-hexane fractions were dried to residue,
      redissolved in mobile phase, and then injected into the HPLC. The HPLC system
      included an acetonitrile-phosphate buffer (62:38, v/v) mobile phase (pH 6.7),
      flow rate of 1.5 mL/min, C(18) column (4.6 mm i.d. x 150 mm length, 5 microm),
      and UV detection at 280 nm. Retention times for rimonabant and doxepin (internal
      standard) were 9.9 and 2.4 min, respectively. The regression of the spiked
      calibrator curve was linear from 60 to 4000 ng/mL (r(2) = 0.996). The lower limit
      of quantification was 60 ng/mL, and recovery was 83.6%. Rimonabant was stable in
      stock solutions and monkey plasma across a range of temperatures and
      concentrations. To demonstrate utility, plasma rimonabant was measured in six
      rhesus monkeys at 60 and 240 min after intramuscular administration of 1 mg/kg
      rimonabant. Rimonabant levels ranged from 175 to 1290 ng/mL. The analytical assay
      described here provides a simple and accurate procedure for multiple within
      subject measurements of the CB(1) antagonist rimonabant.

PMID- 20822667
TI  - Purification of M-MLVH- RT on a 9-aminoethyladenine-(1,6-diamine-hexane)-triazine
      selected from a combinatorial library of dNTP-mimetic ligands.
AB  - Reverse transcriptase (RT) catalyzes the formation of dsDNA from single-stranded
      retroviral RNA genome. This enzyme is unique among DNA polymerases in its ability
      to use either RNA or DNA as a template. Moloney Murine Leukemia virus reverse
      transcriptase lacking RNase H activity (M-MLVH- RT) especially holds particular
      interest because of its ability to eliminate the deleterious effect of RNase H,
      which results in more efficient synthesis of full-length cDNA from mRNA.
      Therefore, the development of a simple purification method attracts the attention
      of retroviral drug and enzyme researchers and manufacturers. The present work is
      the first purification example of a non-tagged (native) RT by affinity
      chromatography using synthetic affinity ligands. In this study, the ligand was
      selected from a structure-biased combinatorial library of dNTP-mimetic ligands,
      and it was evaluated for its ability to bind and purify M-MLVH- RT from inclusion
      bodies of recombinant E. coli. The selected ligand (AEAd), bearing 9
      aminoethyladenine and 1,6-diamine-hexane both linked on the same triazine
      scaffold, displayed the highest enzyme purifying ability after applying mild
      desorption conditions (6 mM MnCl(2) in 20 mM Tris-HCl buffer, pH 7.5). The
      binding capacity of immobilized AEAd with M-MLVH- RT was determined to be equal
      to approximately 1 mg enzyme/g moist weight gel. Adsorption studies with
      immobilized AEAd and soluble M-MLVH- RT demonstrated that the formation of the
      respective complex was perturbed by ATP. Quality control tests of the purified M
      MLVH- RT essentially showed a single band (sodium dodecyl sulfate polyacrylamide
      gel electrophoresis) and absence of nucleic acids and contaminating nuclease
      activities.

PMID- 20822668
TI  - Stereoselective analysis of ritodrine diastereomers in human serum using HPLC.
AB  - A sensitive and selective method has been developed for the determination of
      ritodrine diastereomers in human serum using high-performance liquid
      chromatography with a chiral stationary phase column and a fluorescence detector.
      No interfering peaks from endogenous substances were observed. The method showed
      good reproducibility and accuracy, and the standard curve was linear up to 100
      ng/mL with a correlation coefficient of 0.999. Limit of detection (signal-to
      noise = 3) and quantitation (signal-to-noise = 10) were found to be 2 and 5
      ng/mL, respectively. This method is suitable for chiral pharmacological and
      pharmacokinetic studies as well as the therapeutic drug monitoring of ritodrine
      diastereomers for which no information currently exists.

PMID- 20822669
TI  - LC for analysis of two sustained-release mixtures containing cough cold
      suppressant drugs.
AB  - A liquid chromatographic method was applied for the analysis of two sustained
      release mixtures containing dextromethorphane hydrobromide, carbinoxamine maleate
      with either phenylephrine hydrochloride in pharmaceutical capsules (Mix 1) or
      phenyl-propanolamine, methylparaben, and propylparaben, which bonds as a drug
      base to ion exchange resin in pharmaceutical syrup (Mix 2). The method was used
      for their simultaneous determination using a CN column with a mobile phase
      consisting of acetonitrile-12 mM ammonium acetate in the ratio of 60:40 (v/v, pH
      6.0) for Mix 1 and 45:55 (v/v, pH 6.0) for Mix 2.

PMID- 20822670
TI  - Thin-layer chromatographic mobility of aryl-substituted porphyrins and their
      metalloporphyrins.
AB  - The migration behavior of aryl-substituted porphyrins and their metalloporphyrins
      with Zn(II), Ni(II), and Cu(II) were studied in high-performance thin-layer
      chromatography systems with silica gel and RP(18) plates using different organic
      mobile phases having different polarities. The (bromohydroxy)phenyl,
      (phenoxy)phenyl, and oxy(acetic acid)phenyl porphyrins migrated at similar rate.
      Chloromethylphenylporphyrin was weakly adsorbed on silica gel using either polar
      or nonpolar mobile phases. The mobility of metal complexes generally tends to
      increase in the given order of central metal ions: Zn(II) < Ni(II) < Cu(II) on
      silica gel. The favorable mobile phase for the separation of ligands and the
      metalloporphyrins is a mixture of acetonitrile-benzene.

PMID- 20822671
TI  - Preparation of a novel glycidyl methacrylate-based monolith and its application
      for the determination of m-nisoldipine in human plasma.
AB  - A new method has been developed for preparing monolithic materials by
      polymerisation of the oil-in-water (O/W) emulsions with nonion-surfactant
      (Pluronic F68). Morphology of monolithic materials is studied by scanning
      electron microscopy. The properties of the column are investigated, and the
      column exhibits the ability of low backpressure and fast analysis. Using this
      monolithic column, on-line sample clean-up and screening of m-nisoldipine in
      human plasma samples have been investigated. Chromatography is performed by
      reversed-phase high-performance liquid chromatography (RP-HPLC) on a C(18) column
      with UV detection at 237 nm. The linear range of m-nisoldipine in human plasma is
      2-200 ng/mL (r = 0.9992, n = 7). And the limit of detection is 1.5 ng/mL. The 12
      h pharmacokinetic profile of m-nisoldipine in mice after oral administration has
      been investigated. The results indicate that the method could be used for
      monitoring of m-nisoldipine and enabled simple and rapid assay of the drugs in
      human plasma.

PMID- 20822672
TI  - Identification and quantification of nicotine biomarkers in human oral fluid from
      individuals receiving low-dose transdermal nicotine: a preliminary study.
AB  - The objective of this preliminary study was to identify and quantify potential
      nicotine (NIC) biomarkers in post-exposure oral fluid samples collected from 10
      NIC-abstinent human participants administered 7 mg transdermal NIC using liquid
      chromatography-tandem mass spectrometry (LC-MS-MS). Oral fluid samples were
      collected prior to NIC patch application and at 0.5 and 0.75 h after patch
      removal using the Quantisal() oral fluid collection device. The validated LC-MS
      MS analyte panel included nicotine-Nbeta-D-glucuronide, cotinine-N-oxide, trans-3
      hydroxycotinine, norcotinine, trans-nicotine-1'-N-oxide, cotinine (COT),
      nornicotine, NIC, anatabine, anabasine, and cotinine-N-beta-D-glucuronide.
      Analytes and corresponding deuterated internal standards were extracted by solid
      phase extraction. NIC and COT concentrations were quantifiable in oral fluid
      samples collected from 6 of the 10 participants 0.5 h after patch removal and in
      oral fluid samples collected from 7 of the 10 participants 0.75 h after patch
      removal. Based on the mean NIC and COT concentrations in oral fluid and plasma
      for the participants with both quantifiable NIC and COT at the 0.5 and 0.75 h
      collection times, the oral fluid-plasma ratio was 6.4 for NIC and 3.3 for COT. An
      ELISA procedure was also validated and successfully applied as a screening tool
      for these oral fluid samples in conjunction with LC-MS-MS confirmation. An ELISA
      cut-off concentration of 5.0 ng/mL provided excellent sensitivity for
      discrimination of COT-positive post-exposure oral fluid samples collected after
      low-level transdermal NIC exposure and oral fluid samples collected prior to
      patch application.

PMID- 20822673
TI  - Screening and quantitative determination of twelve acidic and neutral
      pharmaceuticals in whole blood by liquid-liquid extraction and liquid
      chromatography-tandem mass spectrometry.
AB  - We describe a multi-method for simultaneous identification and quantification of
      12 acidic and neutral compounds in whole blood. The method involves a simple
      liquid-liquid extraction, and the identification and quantification are performed
      using liquid chromatography-tandem mass spectrometry. The method was fully
      validated for salicylic acid, paracetamol, phenobarbital, carisoprodol,
      meprobamate, topiramate, etodolac, chlorzoxazone, furosemide, ibuprofen,
      warfarin, and salicylamide. The method also tentatively includes thiopental,
      theophylline, piroxicam, naproxen, diclophenac, and modafinil, but these drugs
      were not included in the full validation program and are not described in detail
      here. Limit of quantitation was 1 mg/kg for the compounds with coefficients of
      variation of < 20%, except for furosemide, which had a coefficient of variation
      of 32% at limit of quantitation. The measuring interval was wide for most
      components. Extraction efficiencies were high, reflecting the high-yield capacity
      of the method.

PMID- 20822674
TI  - Quantification of methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3
      diphenylpyrrolidine in third instar larvae of Lucilia sericata (Diptera:
      Calliphoridae) using liquid chromatography-tandem mass spectrometry.
AB  - Entomotoxicology studies the application of toxicological analysis on
      necrophageous insects present on human remains. This paper describes the
      development and validation of a sensitive liquid chromatography tandem mass
      spectrometry method for quantification of methadone and its main metabolite, 2
      ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), in developmental stages
      of Lucilia sericata. One single larva was pulverized in a disposable vial and
      then extracted with 1-chlorobutane. After evaporation of the organic layer,
      samples were reconstituted in the mobile phase. Chromatographic separation was
      achieved on a NUCLEODUR Sphinx RP column with a liquid chromatographic gradient
      (0.1% formic acid and methanol), ensuring the elution of methadone and EDDP
      within 15 min. The method was fully validated according to international
      guidelines. The use of liquid liquid extraction was demonstrated to be effective
      (matrix effect < 27% and recovery > 66%). The method was linear over the dynamic
      range (10-400 pg/mg larva) with excellent within- and between-run precision and
      bias (CV% < 5%). The lower limit of quantification was fixed at 10 pg/mg larva.
      No instability of the extracted samples was observed in the autosampler after
      three freeze/thaw cycles and after two months at -20 degrees C. The validated
      method was applied to third instar larvae of Lucilia sericata reared on beef
      heart spiked with 4 microg/g methadone and on a postmortem methadone overdose
      case. The validation and actual sample analysis showed that the method is
      sensitive, rugged, precise, accurate, and well-suited for routine analysis of
      methadone and EDDP in a single larva obtained from forensic cases.

PMID- 20822675
TI  - Uptake and distribution of the abused inhalant 1,1-difluoroethane in the rat.
AB  - 1,1-Difluoroethane (DFE) is a halogenated hydrocarbon used as a propellant in
      products designed for dusting electronic equipment and air brush painting. When
      abused, inhaled DFE produces intoxication and loss of muscular coordination. To
      investigate DFE toxicokinetics, groups (n = 3) of Sprague-Dawley rats were
      exposed to 30 s of 20 L/min DFE. The experimental model was designed to mimic
      exposure during abuse, a protocol which has not been conducted. Tissue collection
      (blood, brain, heart, liver, and kidney) occurred at 0, 10, 20, 30, 45, 60, 120,
      240, 480, and 900 s. Average peak DFE levels were blood 352, brain 519, heart
      338, liver 187, and kidney 364 mg/L or mg/kg. The total percent uptake of the
      administered dose was 4.0%. Uptake into individual compartments was 2.72, 0.38,
      0.15, 0.41, and 0.32% for blood, brain, heart, liver, and kidney, respectively.
      All animals showed signs of intoxication within 20 s manifested as lethargy,
      prostration and loss of righting reflex. Marked intoxication continued for about
      4 min when DFE averaged 21 mg/L in blood and 17 mg/kg in brain. Between 4 and 8
      min, animals continued to show signs of sedation as evidenced by reduced
      aggression and excitement during handling. No discernable intoxication was
      evident after 8 min and blood and brain levels had fallen to 10 and 6 mg/L or kg,
      respectively. Plots of concentration (log) versus time were consistent with a two
      compartment model. Initial distribution was rapid with average half life
      (t((1/2))) during the alpha phase of 9 s for blood, 18 s for brain and 27 s in
      cardiac tissue. During beta slope elimination average t((1/2)) was 86 s in blood,
      110 s in brain and 168 s in heart. Late elimination half lives were longer with
      blood gamma = 240 s, brain gamma = 340 s, and heart gamma = 231 s. Following
      acute exposure the Vd = 0.06 L, beta = 0.48 min(-1), AUC = 409.8 mg.min L(-1),
      and CL from blood was 0.03 L min(-1). The calculated toxicokinetic data may
      underestimate these parameters if DFE is abused chronically due to continued
      uptake into lowly perfused tissues with repeated dosing.

PMID- 20822676
TI  - A simple and sensitive method for the determination of propofol in human solid
      tissues by gas chromatography-mass spectrometry.
AB  - Propofol is a widely used intravenous agent for induction and maintenance of
      anesthesia and for sedation in intensive care patients, but it is also associated
      with abuse and dependency. A simple and sensitive method for the determination of
      propofol in human whole blood, brain, liver, and adipose tissue by gas
      chromatography-mass spectrometry using selected-ion monitoring mode is described.
      Propofol was extracted from 0.2-mL or 0.2-g sample size by a single-step basic
      extraction procedure using 100 microL heptane with thymol (50 ng) as an internal
      standard. The calibration curves of the specimens were linear in the
      concentration range of 10-5000 ng/mL or ng/g, and the limit of detection was 2.5
      ng/mL in blood, 5.0 ng/g in brain and liver, and 10 ng/g in adipose tissue.
      Absolute recovery of propofol was determined in three samples and averaged over
      95% for blood and brain, 66% for liver, and 51% for adipose tissue. Within-day
      and between-day precision was measured in five samples each at 50 and 500 ng/mL
      or ng/g in all specimens and was determined to be less than 10%. The developed
      propofol method was applied to a forensic autopsy case where a suspected propofol
      misinjection occurred eight days prior to death, and the tissue analysis was
      vital to the case.

PMID- 20822677
TI  - Urinary concentrations of gamma-hydroxybutyric acid and related compounds in
      pregnancy.
AB  - Endogenous production complicates the interpretation when gamma-hydroxybutyric
      acid (GHB) is measured in urine for forensic purposes. We performed a cross
      sectional study to test the hypothesis that pregnant women have higher levels of
      urinary GHB than non-pregnant controls, and thus increased risk of false-positive
      GHB tests. GHB, gamma-butyrolactone (GBL) and beta-hydroxybutyric acid (BHB)
      concentrations in urine from 66 pregnant women and 69 non-pregnant controls were
      analyzed by liquid chromatography-tandem mass spectrometry (LC-MS-MS). The mean
      GHB, GBL, and BHB concentrations were 0.36, 0.34 and 1.92 mg/L in the pregnant
      women, and 0.24, 0.08 and 0.40 mg/L in the control group. The pregnant women had
      significantly higher levels of GHB (1.5-fold), GBL (4.3-fold), and BHB (4.8
      fold). Creatinine-adjusted GHB concentrations were similar in both groups.
      Pregnant women have higher urinary levels of GHB, GBL, and BHB. In LC-MS-MS
      assays not distinguishing between GHB and BHB, there is a significantly increased
      risk of false-positive GHB tests in pregnant women. This false-positive rate can
      be reduced by correcting for creatinine concentration, by using GHB-specific
      assays or by introducing higher interpretative cut-off levels for pregnant women
      in assays that do not discriminate between GHB and GBL or BHB.

PMID- 20822678
TI  - Correlations between phthalate metabolites in urine, serum, and seminal plasma
      from young Danish men determined by isotope dilution liquid chromatography tandem
      mass spectrometry.
AB  - Phthalates are suspected of endocrine disrupting effects. We aimed to develop an
      analytical method for simultaneous determination of several phthalate metabolites
      in human urine, serum, and seminal plasma and to study correlations between
      levels of metabolites in these matrices. Thirteen metabolites were determined in
      samples from 60 young Danish men. Metabolites of common di-ester phthalates were
      detected in most urine samples. Summed di-(2-ethylhexyl) phthalate (DEHP)
      metabolites were excreted in urine in the highest amount (median = 91.1 ng/mL),
      followed by monoethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP), mono-n
      butyl phthalate (MnBP), mono-benzyl phthalate (MBzP), and finally summed di
      isononyl phthalate (DiNP) metabolites. All these metabolite levels correlated
      significantly, indicating that when a participant was highly exposed to one
      phthalate he was also highly exposed to other phthalates. Several metabolites
      were also detectable in serum and in seminal plasma, although in much lower
      levels. Significant correlations between MEP and MiBP levels in serum and urine
      were observed, showing that serum levels could be used as biomarkers of human
      exposure. For DEHP and DiNP metabolites, correlations between urine and serum
      levels were only observed for mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) and
      mono-(4-methyl-7-carboxyheptyl) phthalate (MCiOP), indicating that these
      secondary carboxylated metabolites were better serum markers than primary
      metabolites [mono(2-ethylhexyl) phthalate (MEHP) and mono-iso-nonyl phthalate
      (MiNP)]. In seminal plasma, only MEP levels correlated significantly to levels in
      urine and in serum.

PMID- 20822679
TI  - Stability of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)
      1-butanol in urine samples stored at various temperatures.
AB  - Urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and NNAL
      glucuronide, which are metabolites of the tobacco-specific nitrosamine 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are valuable biomarkers of
      tobacco exposure. In epidemiologic investigations, it is often necessary for
      samples to be collected and stored for various periods of time prior to analysis,
      and as a consequence, it is important to determine the stability of these
      analytes during storage. In this study, two urine pools were stored at six
      different temperatures ranging from -70 degrees C to 55 degrees C. Free NNAL and
      NNAL-glucuronide were measured at scheduled time intervals for 28 days, after
      which samples stored at -20 degrees C and -70 degrees C were further monitored
      for an additional four years. NNAL-glucuronide was not completely stable at room
      temperature (ca. 22 degrees C) or above. At those temperatures, a gradual loss of
      NNAL-glucuronide with concomitant increases in free NNAL was observed. However,
      both free NNAL and NNAL-glucuronide appeared to be stable for at least four weeks
      when stored in the refrigerator (4 degrees C) and for at least four years at -20
      degrees C and -70 degrees C, respectively. These results suggest that valid NNAL
      concentrations can be measured in frozen urine samples that have been stored for
      an extended period of time prior to analysis.

PMID- 20822680
TI  - The prevalence of alcohol and drugs in sampled oral fluid is related to sample
      volume.
AB  - About 22,000 samples of oral fluid have been collected in five population studies
      in Norway using either the Intercept or Statsure oral fluid sampling devices. The
      prevalence of alcohol and drugs was found to be higher in oral fluid samples with
      small volumes than in those with large volumes for both sampling devices; the
      largest differences were observed for tetrahydrocannabinol, alcohol,
      amphetamines, and cocaine/benzoylecgonine when using the Statsure device. Our
      recommendation is that samples of oral fluid with smaller volume than required by
      the analytical methods should not be discarded, but instead be analyzed using a
      smaller sample volume, if necessary, after dilution. If not analyzed, positive
      drug cases will be missed, and the total prevalence of alcohol and drugs in the
      population being studied will be underestimated.

PMID- 20822681
TI  - Comparison of ethanol and other drugs of abuse concentrations in whole blood
      stored in venoject glass and plastic and venosafe plastic evacuated tubes.
AB  - The aim of this study was to evaluate the stability of blood concentrations of a
      variety of illegal and medicinal drugs that are important for forensic analyses
      when spiked and stored in Vacutainer or Venosafe evacuated plastic collection
      tubes compared to Vacutainer evacuated glass tubes. Tubes were filled with spiked
      whole blood and analyzed after storage for one week at ambient temperature and at
      -20 degrees C, respectively. Freeze-and-thaw stability was included in the study.
      No significant difference between storage in glass or plastic tubes was noted for
      any compound investigated.

PMID- 20822682
TI  - Low exercise among children with asthma: a culture of over protection? A
      qualitative study of experiences and beliefs.
AB  - BACKGROUND: Research shows that children are insufficiently active in most
      affluent societies. Although children with asthma may particularly benefit from
      physical activity, they are less active than their peers. AIM: To explore the
      reasons for low physical activity levels among children with asthma and to
      identify strategies to improve activity. DESIGN OF STUDY: A qualitative study
      using in-depth interviews and focus groups. SETTING: Six GP practices, a
      Paediatric Respiratory Unit, and four schools in Tayside, Scotland. METHOD:
      Purposive sampling identified 30 children with asthma, their parents (n = 38) and
      school staff (n = 28), who were interviewed or took part in focus groups. Data
      were examined using constant comparative analysis. RESULTS: The lower level of
      activity among children with asthma was supported by a climate of fear among
      parents and teachers about what was safe and possible for the child. Restrictions
      were imposed because of perceived dangers of exercising in the presence of
      'triggers'. Physical activity was regarded as a threat to be managed rather than
      something beneficial. Teachers found it difficult to distinguish between children
      who were physically incapable of exercise due to asthma and those who were
      unmotivated. GPs were unknowingly drawn into the controversy by children and
      parents who cite medical advice to sanction exemption from exercise. CONCLUSION:
      GPs and asthma nurses need to provide clear management plans explaining what is
      appropriate and safe in terms of exercise on a child-by-child basis, to counter
      the considerable misunderstanding and disagreement among children, parents, and
      teachers.

PMID- 20822685
TI  - The exercise prescription.

PMID- 20822683
TI  - A simple risk score using routine data for predicting cardiovascular disease in
      primary care.
AB  - BACKGROUND: Population-based screening for cardiovascular disease (CVD) risk,
      incorporating blood tests, is proposed in several countries. AIM: The aim of this
      study was to evaluate whether a simple approach to identifying individuals at
      high risk of CVD using routine data might be effective. DESIGN OF STUDY:
      Prospective cohort study (EPIC-Norfolk). SETTING: Norfolk area, UK. METHOD: A
      total of 21 867 men and women aged 40-74 years, who were free from CVD and
      diabetes at baseline, participated in the study. The discrimination (the area
      under the receiver operating characteristic curve [aROC]), calibration,
      sensitivity/specificity, and positive/negative predictive value were evaluated
      for different risk thresholds of the Framingham risk equations and the Cambridge
      diabetes risk score (as an example of a simple risk score using routine data from
      electronic general practice records). RESULTS: During 203 664 person-years of
      follow-up, 2213 participants developed a first CVD event (10.9 per 1000 person
      years). The Cambridge diabetes risk score predicted CVD events reasonably well
      (aROC 0.72; 95% confidence interval [CI] = 0.71 to 0.73), while the Framingham
      risk score had the best predictive ability (aROC 0.77; 95% CI = 0.76 to 0.78).
      The Framingham risk score overestimated risk of developing CVD in this
      representative British population by 60%. CONCLUSION: A risk score incorporating
      routinely available data from GP records performed reasonably well at predicting
      CVD events. This suggests that it might be more efficient to use routine data as
      the first stage in a stepwise population screening programme to identify people
      at high risk of developing CVD before more time- and resource-consuming tests are
      used.

PMID- 20822686
TI  - Impact of lifestyle in middle-aged women on mortality: one article and many
      questions.

PMID- 20822687
TI  - Cardiovascular disease beyond the QOF.

PMID- 20822688
TI  - Citation, citation, citation.

PMID- 20822689
TI  - Impact of lifestyle in middle-aged women on mortality: evidence from the Royal
      College of General Practitioners' Oral Contraception Study.
AB  - BACKGROUND: Although many individuals have multiple lifestyle risk factors, few
      studies have investigated the impact of lifestyle risk factor combinations among
      women. AIM: To investigate the relationship between individual and combinations
      of lifestyle risk factors in middle-aged women with subsequent mortality, and to
      estimate the associated population attributable risks. DESIGN OF STUDY:
      Prospective cohort study. SETTING: Royal College of General Practitioners' (RCGP)
      Oral Contraception Study, UK. METHOD: In 1994-1995, women remaining under follow
      up in the RCGP Oral Contraception Study were sent a lifestyle survey, from which
      modifiable risk factors were identified: pack-years smoked, physical inactivity,
      never drinking versus consuming at least 7 units of alcohol weekly, and being
      underweight, overweight, or obese. The cohort was followed to December 2006 or
      death. Population attributable risks were calculated. RESULTS: Of 10 059 women
      studied, 896 died. Pack-years smoked (11-20 years: adjusted hazard ratio [HR] =
      1.82, 95% confidence interval [CI] = 1.46 to 2.27; >20 years: adjusted HR = 2.34,
      95% CI = 2.00 to 2.74); never drinking alcohol (adjusted HR = 1.66, 95% CI = 1.34
      to 2.05); being underweight (adjusted = HR 1.66, 95% CI = 1.03 to 2.68); and
      physical inactivity (<15 hours/week: adjusted HR = 1.73, 95% CI = 1.46 to 2.04)
      were significantly associated with mortality compared with their respective
      reference group. Women with multiple lifestyle risk factors had higher mortality
      risks than those reporting one factor. The population attributable risk of the
      combination of smoking, physical inactivity, body mass index outside normal
      range, and alcohol (never drinking or excess intake) was 59% (95% CI = 31% to
      78%). CONCLUSION: Assuming a causal relationship between lifestyle and mortality,
      avoidance of four lifestyle risk factors would have prevented 60% of the deaths.
      The importance of avoiding smoking and undertaking physical inactivity during
      midlife should continue to be emphasised.

PMID- 20822690
TI  - Type 2 diabetes and dog walking: patients' longitudinal perspectives about
      implementing and sustaining physical activity.
AB  - BACKGROUND: Physical activity is particularly important for people with type 2
      diabetes, as evidence suggests that any reduction in sedentary time is good for
      metabolic health. AIM: To explore type 2 diabetes patients' talk about
      implementing and sustaining physical activity. DESIGN OF STUDY: Longitudinal,
      qualitative study using repeat in-depth interviews with 20 patients over 4 years
      following clinical diagnosis. SETTING: Patients were recruited from 16 general
      practices and three hospitals across Lothian, Scotland. RESULTS: Discussion, and
      salience, of physical activity was marginal in patient accounts of their diabetes
      management. Patients claimed to have only received vague and non-specific
      guidance about physical activity from health professionals, and emphasised a
      perceived lack of interest and encouragement. Aside from walking, physical
      activities which were adopted tended to attenuate over time. Patients' accounts
      revealed how walking a dog assisted this kind of activity maintenance over time.
      Three main themes are highlighted in the analysis: 1) incidental walking; 2)
      incremental physical activity gains; and 3) augmenting physical activity
      maintenance. The problems arising from walking without a dog (for example, lack
      of motivation) are also examined. CONCLUSION: Asking patients about pet
      preferences might seem tangential to medical interactions. However, encouraging
      dog walking or identifying another interest that promotes a regular commitment to
      undertake physical activity may yield long-term health benefits.

PMID- 20822691
TI  - Cardiovascular events in patients with obesity: an observational study.
AB  - BACKGROUND: Overweight and obesity are positively correlated with increased risk
      of morbidity and mortality. AIM: To evaluate whether obesity may be considered an
      independent cardiovascular risk factor in patients of ages from 35 to 74 years
      followed-up for 10 years. DESIGN OF STUDY: Observational, longitudinal
      retrospective study. SETTING: Primary care practices in Badajoz (Spain). METHOD:
      A cohort of 899 patients (mean 55.7 years; 58.2% female) without evidence of
      cardiovascular disease was studied. RESULTS: A total of 33.5% of the population
      were obese (body mass index > or =30 kg/m2). Patients meeting the obesity
      criteria were more commonly female (36.6%) and were older, had higher mean values
      of blood pressure and triglycerides, higher percentages of diabetes, and higher
      coronary risk using either the original Framingham or the Framingham function
      calibrated for the Spanish population (Framingham-REGICOR). During the follow-up
      period, the rates of cardiovascular events and death in patients with obesity
      tended to be higher: 16.3% versus 11.7%, P = 0.056 and 4.7% versus 2.2%, P<0.05,
      respectively. In the final model of the logistic regression multivariate
      analysis, the significant predictors of cardiovascular events in patients with
      obesity were age, sex (male), diastolic blood pressure, diabetes, and smoking.
      The highest odds ratio corresponded to smoking (odds ratio 2.03; 95% confidence
      interval = 1.22 to 3.38). CONCLUSION: Obesity may not be considered an
      independent cardiovascular risk factor in patients aged from 35 to 74 years
      followed-up for 10 years.

PMID- 20822692
TI  - Perceptions of joint pain and feeling well in older people who reported being
      healthy: a qualitative study.
AB  - BACKGROUND: Older people often view osteoarthritis as a part of normal ageing and
      see themselves as healthy despite painful joints. Professionals have mixed views
      about this. One concern is that seeing osteoarthritis as a result of 'wear and
      tear' leads to restricting exercise in order to avoid further wear. AIM: To
      explore lay perceptions of wellness and joint pain, and their implications for
      consulting healthcare professionals and taking exercise. DESIGN OF STUDY:
      Qualitative, longitudinal study. SETTING: General practice in the North Midlands.
      METHOD: Semi-structured interviews with 27 older people who reported a joint
      problem but rated themselves as healthy. Diary sheets were sent for 11
      consecutive months to record changes in health and circumstances. Thematic data
      analysis was facilitated by NVivo 8. RESULTS: A key element of wellness was being
      able to continue with everyday roles and activities. 'Wear and tear' was used to
      categorise arthritis that is a normal part of old age. New joint symptoms that
      came on suddenly and severely were not necessarily attributed to 'wear and tear'
      arthritis, and were likely to lead to a professional consultation. Physical
      activity was not restricted to prevent further wear of affected joint(s). Keeping
      joints mobile was important in order to maintain independence. CONCLUSION:
      Professionals should explore patients' ideas and concerns about their joint
      problem, in order to individually tailor explanations and advice. Patients are
      likely to be receptive to recommendations that promote independence, but advice
      needs to be set into patients' existing ways of living and coping with joint
      pain.

PMID- 20822693
TI  - GPs and involuntary admission: a qualitative study.
AB  - BACKGROUND: In many countries, medical authorities are responsible for
      involuntary admissions of mentally ill patients. Nonetheless, very little is
      known about GPs' experiences with involuntary admission. AIM: The aim of the
      present study was to explore GP's experiences from participating in involuntary
      admissions. SETTING: General practice, Aarhus, Denmark. METHOD: One focus group
      interview and six individual interviews were conducted with 13 Danish GPs, who
      had recently sectioned one of their own patients. RESULTS: GPs experienced stress
      and found the admission procedure time consuming. They felt that sectioning
      patients was unpleasant, and felt nervous, but experienced relief and
      professional satisfaction if things went well. The GPs experienced the doctor
      patient relationship to be at risk, but also reported that it could be improved.
      GPs felt that they were not taken seriously by the psychiatric system.
      CONCLUSION: The unpleasant experiences and induced feelings resulting from
      involuntary admissions reflect an undesirable and stressful working environment.

PMID- 20822694
TI  - NICE clinical guideline: chest pain of recent onset.

PMID- 20822695
TI  - Clinical burden and health service challenges of chronic heart failure.

PMID- 20822696
TI  - Hypertension in Pakistan.

PMID- 20822697
TI  - Detection of congenital heart disease in mid-Essex.

PMID- 20822698
TI  - Access to computed tomography.

PMID- 20822699
TI  - Are 'polysystems' for doctors or patients?

PMID- 20822701
TI  - Academic general practice: reflections on a 60-year journey.

PMID- 20822707
TI  - A clinical prediction rule combining routine assessment and power Doppler
      ultrasonography for predicting progression to rheumatoid arthritis from early
      onset undifferentiated arthritis.
AB  - OBJECTIVES: The ability to predict the development of rheumatoid arthritis (RA)
      in patients with an early-onset undifferentiated arthritis (UA) is highly
      required if the remission or an adequate response to the treatment are the main
      goal. The aim of the study was to develop a predictive rule combining clinical
      variables, serological biomarkers and power Doppler ultrasonography (PDUS) for
      the progression from an early-onset UA to RA in daily rheumatological practice.
      METHODS: A prediction rule was developed after a 12 months study of 149 adult
      patients with a recent-onset UA. The combination of routine assessment variables
      and PDUS findings was investigated. Logistic regression analysis was performed to
      identify the independent factors for the development of RA and global predictive
      score was calculated. The score of the predictive rule ranged from 0 to 10. The
      area under the receiver operating characteristic curve was used to evaluate the
      diagnostic performance of the rule. The post-test probability (post-TP) was
      evaluated using the Bayes theorem. RESULTS: Sixty-two patients (41.6%) developed
      a RA. The rule demonstrated excellent discriminative ability, with an AUC of
      0.919 (p=0.0001). With the optimal cut-off point of 5, sensitivity was 89.9%,
      specificity was 88.6% and positive likelihood ratio was 7.89. If a threshold of
      6.5 was applied a higher value of specificity (97.7%) was obtained, but
      sensitivity (47.6%) decreased. The post-TP value of the two different cut-off
      points mentioned above were 62% and 80%, respectively. CONCLUSIONS: Our
      predictive rule, which includes PDUS assessment, revealed an excellent
      discriminative ability for assessing the likelihood of development of RA in
      patients with an early-onset UA. Further studies are required to confirm the
      results and to tailor a therapeutic approach in patients with an early-onset UA.

PMID- 20822708
TI  - Risk of tuberculosis in patients with rheumatoid arthritis in Hong Kong--the role
      of TNF blockers in an area of high tuberculosis burden.
AB  - OBJECTIVES: To elucidate the incidence rate and relative risk of tuberculosis
      (TB) in patients with rheumatoid arthritis (RA) compared to the general
      population in Hong Kong between 2004 and 2008, and to assess whether this risk is
      associated with exposure to tumour necrosis factor (TNF) blockers after adjusting
      for other known risk factors. METHODS: We reviewed all the medical records of RA
      patients to determine the standardised incidence ratio (SIR) of TB in RA
      patients. Independent explanatory variables associated with active TB in RA were
      ascertained using the Cox regression model. RESULTS: A total of 2441 RA patients
      followed at the 5 centres were recruited. The mean age at the start of follow up
      was 56+/-14 years. The median follow-up duration was 6,616 and 185 patient-years
      for the TNF naive and TNF treated groups, respectively. Compared to age- and sex
      matched population controls, the SIR of active TB in RA was significantly
      increased (SIR for TNF naive RA: 2.35, 95% CI 1.17-4.67, p=0.013, SIR for TNF
      treated RA: 34.92, 95% CI 8.89-137.20, p<0.001). Independent explanatory
      variables associated with an increase risk of active TB included older age at
      study entry (RR 1.05, p=0.013) a past history of pulmonary TB (RR 5.48, p=0.001),
      extra-pulmonary TB (RR 16.45, p<0.001), Felty's syndrome (RR 43.84, p=0.005),
      prednisolone>10mg daily (RR 4.44, p=0.009) and the use of TNF blockers (RR 12.48,
      p<0.001). CONCLUSIONS: Exposure to TNF blockers remained to be an independent
      risk factor for TB in RA after adjusting for other known risk factors.

PMID- 20822709
TI  - Italian validation of the Wagnild and Young Resilience Scale: a perspective to
      rheumatic diseases.
AB  - OBJECTIVES: Studying the characteristics of resilience may help to explain how,
      in the face of a chronic disease, people are able to cope in productive and
      effective ways. The Wagnild and Young Resilience Scale (RS) is an appropriate
      instrument to study resilience and has already been translated from the original
      English version into several languages. The aim of this study was to validate the
      Italian version of the RS, a 25-item scale ranging from 25 to 175 where higher
      scores indicate stronger resilience. METHODS: The Minimal Translation Criteria
      were followed to translate the scale which was then filled out by 1090 students
      to assess the reliability, stability, internal consistency and concurrent
      validity. RESULTS: Time stability was assessed in a sample of 117 students (M
      age=20.18 yr, SD 1.25) by test-retest correlation (r=0.78). RS reliability was
      evaluated in a second sample of 973 students (M age=16.95 yr, SD 1.50) with RS
      mean of 126.6 (SD 17.4). Concurrent validity was assessed by correlation with
      General Health Questionnaire (r=-0.51), Ego-Resilience Scale (r=0.63) and Beck
      Depression Inventory (r=-0.45). Internal consistency was evaluated by Cronbach
      alpha (alpha=0.84). Principal component analysis was performed on 24 out of the
      25 items and resulted in six components. CONCLUSIONS: Our data indicated that the
      24-item Italian version of the RS scale can be considered a useful instrument to
      measure resilience and can be used by healthcare staff to help patients cope
      effectively with stressful situations such as rheumatic and other chronic
      diseases.

PMID- 20822710
TI  - Functional evaluation of TNFAIP3 (A20) in rheumatoid arthritis.
AB  - OBJECTIVES: To determine the protein expression of TNFAIP3 in synovium and to
      show the capability of 6q23 intergenic SNPs, associated with rheumatoid arthritis
      (RA) susceptibility, to influence TNFAIP3 gene transcription. METHODS:
      Immunohistochemistry for TNFAIP3, NF-kB p65 and phosphorylated NF-kB p65 protein
      expression was performed in 6 RA knee joint synovium samples compared to 9
      osteoarthritis (OA) samples. Luciferase reporter gene assays were used to examine
      the regulatory ability of RA associated SNP variants on TNFAIP3 promoter
      activity. Sense and antisense constructs were prepared for rs6920220 alleles,
      together with each of the 4 SNPs in r2=1 with it (rs6933404, rs2327832, rs6927172
      and rs17264332), coupled to the TNFAIP3 promoter. Transient transfections were
      performed in a human T lymphoblastoid (CEMC7A) cell line. Bioinformatic software
      was utilised to prioritise SNPs for further investigation. Electrophoretic
      mobility shift assays (EMSA), using CEMC7A nuclear extracts, were conducted for
      the rs6927172 SNP alleles. RESULTS: TNFAIP3 protein expression was seen in the
      synovium samples and differential TNFAIP3 protein expression between RA vs. OA
      synoviocytes observed. Within RA synoviocytes TNFAIP3 expression is predominately
      cytoplasmic, whereas in OA its expression is strongly nuclear and cytoplasmic.
      For 3 of the 5 SNPs investigated (rs6920220, rs6933404, rs6927172) evidence of
      repressor activity of TNFAIP3 transcription was seen and EMSA data showed
      evidence of differential transcription factor binding to rs6927172 alleles.
      CONCLUSIONS: This is the first observation of TNFAIP3 protein expression in RA
      and OA synovium. In vitro analysis of 6q23 intergenic SNPs supports the
      possibility of the functional regulation of TNFAIP3.

PMID- 20822711
TI  - The formation of autoantibodies and antibodies to TNF-alpha blocking agents in
      relation to clinical response in patients with ankylosing spondylitis.
AB  - OBJECTIVES: To investigate the influence of antibody formation to TNF-alpha
      blocking agents on the clinical response in AS patients treated with infliximab
      (IFX), etanercept (ETA), or adalimumab (ADA), and to investigate the development
      of ANA, ANCA, and anti-dsDNA antibodies in association with the formation of
      antibodies to TNF-alpha blocking agents. METHODS: Consecutive AS outpatients with
      active disease who started treatment with IFX (n=20), ETA (n=20), or ADA (n=20)
      were included in this longitudinal observational study. Clinical data were
      collected prospectively at baseline and after 3, 6, and 12 months of anti-TNF
      alpha treatment. At the same time points, serum samples were collected. In these
      samples, antibodies to TNF-alpha blocking agents, serum TNF-alpha blocker levels,
      and ANA, ANCA, and anti-dsDNA antibodies were measured retrospectively. RESULTS:
      Anti-IFX, anti-ETA, and anti-ADA antibodies were induced in 20%, 0%, and 30% of
      patients, respectively. Although ANA, ANCA, and anti-dsDNA antibodies were
      detected during anti-TNF-alpha treatment, no significant association was found
      between the presence of these autoantibodies and the formation of antibodies to
      TNF-alpha blocking agents. Patients with anti-IFX or anti-ADA antibodies had
      significantly lower serum TNF-alpha blocker levels compared to patients without
      these antibodies. Furthermore, significant negative correlations were found
      between serum TNF-alpha blocker levels and assessments of disease activity.
      CONCLUSIONS: This study indicates that antibody formation to IFX or ADA is
      related to a decrease in efficacy and early discontinuation of anti-TNF-alpha
      treatment in AS patients. Furthermore, autoantibody formation does not seem to be
      associated with antibody formation to TNF-alpha blocking agents.

PMID- 20822712
TI  - Lack of association of PTPN22, STAT4 and TRAF1/C5 gene polymorphisms with
      cardiovascular risk in rheumatoid arthritis.
AB  - OBJECTIVES: To determine whether the PTPN22, STAT4 and TRAF1/C5 gene
      polymorphisms may be implicated in the development of cardiovascular (CV) events
      and subclinical atherosclerosis manifested by the presence of endothelial
      dysfunction or increased carotid intima-media thickness (IMT) in a series of
      Spanish patients with rheumatoid arthritis (RA). METHODS: Six hundred and twelve
      patients fulfilling the 1987 American College of Rheumatology classification
      criteria for RA, seen at the rheumatology outpatient clinics of Hospital Xeral
      Calde, Lugo, and Hospital San Carlos, Madrid, were studied. Patients were
      genotyped using predesigned TaqMan single nucleotide polymorphism genotyping
      assays. Moreover, between March and December 2007, a subgroup of unselected RA
      patients with no history of CV events was studied for the presence of subclinical
      atherosclerosis by the assessment of the endothelial function (n=126) and the
      carotid artery IMT (n=110) by ultrasonography studies. RESULTS: No significant
      differences in the allele or genotype frequencies for the PTPN22, STAT4 and
      TRAF1/C5 gene polymorphisms between RA patients with or without CV events were
      found. It was also the case when we analysed the potential influence of the
      genotypes in the presence of endothelial dysfunction or increased carotid artery
      IMT of patients with RA. CONCLUSIONS: Our results do not show that the PTPN22,
      STAT4 and TRAF1/C5 gene polymorphisms may confer a direct risk of CV disease in
      patients with RA.

PMID- 20822713
TI  - Serum levels of long pentraxin PTX3 in patients with polymyalgia rheumatica.
AB  - OBJECTIVES: To evaluate PTX3 feasibility to provide a prognostic tool in PMR
      clinical practice. METHODS: Circulating PTX3 levels were measured in 93 PMR
      patients at disease onset and during corticosteroid therapy and in 46 normal
      controls (NC) by ELISA. RESULTS: No difference in PTX3 concentrations was
      observed between NC and PMR either at disease onset and during follow-up or
      between groups of patients defined according to the presence of
      recurrence/relapse. CONCLUSIONS: PTX3 serum levels do not increase significantly
      in active PMR. Further studies on patients with giant-cell arteritis could
      evaluate whether large vessel involvement may be associated to increased PTX3
      levels.

PMID- 20822714
TI  - Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis involving the
      central nervous system: case report and review of the literature.
AB  - OBJECTIVES: To report a case of biopsy-proven, ANCA-associated vasculitis (AAV)
      involving the central nervous system (CNS) and to review the relevant literature.
      METHODS: Descriptive case report of one patient with AAV-related CNS vasculitis
      and review of the relevant literature (PubMed search from 1966 to February 2010).
      RESULTS: A 61-year-old female patient with AAV developed cognitive impairment.
      Cerebrospinal fluid analysis was unremarkable, while magnetic resonance (MR)
      imaging showed multiple left hemisphere infarctions and MR angiography revealed
      multiple stenoses of the distal branches of the left median cerebral artery.
      Treatment with glucocorticoids, cyclophosphamide, and intravenous immunoglobulins
      led to improvement. CNS vasculitis often arises when vasculitis is active
      elsewhere. There is no clear preponderance of gender or of age of onset. Both
      ANCA-positive and -negative cases of CNS vasculitis are documented. The diagnosis
      is usually based on clinical CNS manifestations and multiple ischaemic (sometimes
      haemorrhagic) MR lesions mainly affecting the white matter. Angiography is often
      negative. Treatment with glucocorticoids and cyclophosphamide, sometimes with
      adjunctive intravenous immunoglobulins, usually improves clinical features and MR
      lesions. CONCLUSIONS: AAV rarely involves the CNS. CNS vasculitis should be
      suspected if patients have neurological manifestations consistent with CNS
      involvement, particularly if they have evidence of disease activity elsewhere,
      and if MR shows multiple ischaemic (sometimes haemorrhagic) lesions mainly
      affecting the white matter. Sepsis, coagulation disorders, and severe
      hypertension must be ruled out. Awareness of this rare but severe complication
      can allow early recognition and prompt treatment.

PMID- 20822715
TI  - Neuropsychiatric aid in children born to patients with rheumatic diseases.
AB  - A chronic disease may have an adverse impact on patients' quality of life and on
      their relationship styles. If this occurs in a mother, the related emotional and
      physical distress can interfere with baby holding, impacting on the antenatal
      maternal-foetal attachment and on the upbringing and development of the baby.
      Ineffective holding leads to the persistence of a condition of 'vulnerability to
      stress' and the possible development of psychosomatic problems in the offspring.
      In this paper we present our experience and a review from the current literature
      on the psychological aspects of pregnancy and parenthood in women with rheumatic
      diseases (RD) and children's development. To ameliorate family global quality of
      life, different experts (the rheumatologist, the obstetric, the neonatologist,
      the psychologist and the neuropsychiatric experts) should cooperate in teamwork
      to keep the patients' needs integrated. In particular, the neuropsychiatric
      intervention might support the patients and their partners throughout the
      experience of pregnancy and parenthood and prevent the occurrence of
      psychopathologic traits.

PMID- 20822716
TI  - Prevalence of antibodies against mutated citrullinated vimentin and cyclic
      citrullinated peptide in children with juvenile idiopathic arthritis.

PMID- 20822717
TI  - Interpreting the Carotid Revascularization Endarterectomy Versus Stent Trial
      (CREST): additional trials are needed.

PMID- 20822718
TI  - Thoracic aortic trauma: outcomes and hospital resource utilization after
      endovascular and open repair.
AB  - Thoracic endovascular aortic repair (TEVAR) has evolved as a treatment option for
      the management of thoracic aortic trauma as an alternative to open thoracic
      aortic repair (OTAR). Population-level outcomes are not known and were evaluated.
      Secondary data analysis of the 2005-2006 Nationwide Inpatient Sample data was
      performed, and 1,561 patients with thoracic aortic injury (mean age 44.8 +/- 18.8
      years; men 77.2%) were identified. Of these, 510 underwent emergent surgical
      intervention: 240 OTAR (47%) and 270 TEVAR (53%). Males were more likely to
      undergo any surgery (77.2% vs 22.8%; p = .03). Hospital mortality after OTAR was
      greater compared to TEVAR (14.61% vs 7.43%; p = .009). OTAR patients were more
      likely to have pulmonary complications (37.8% vs 21.65; p < .0001) but were less
      likely to have stroke (2.1% vs 5.8%; p = .03) compared to TEVAR patients. After
      adjustment, OTAR patients remained more likely to die compared to TEVAR patients
      (OR 11.5; 95% CI 4.0-33.2). Hospital length of stay and hospital cost were
      significantly greater for OTAR than for TEVAR. An increase in patients with
      thoracic aortic injury undergoing repair was found (23.0% vs 40.3%; p < .0002).
      In trauma, TEVAR was associated with decreased hospital mortality, hospital use,
      and pulmonary complications but increased rates of stroke. Further implementation
      of TEVAR for management of thoracic aortic trauma may improve future outcomes and
      reduce hospital resource use.

PMID- 20822719
TI  - Effect of anastomotic length on the development of intimal hyperplasia in the
      distal anastomosis of bypass graft.
AB  - Many hemodynamic factors have been shown to be associated with increased intimal
      hyperplasia at the distal anastomosis of arterial bypass graft. However, the
      relationship between the length of anastomosis and the development of such a
      complication has not been studied before. The aim of this study was to assess
      this relationship at the distal anastomosis with a Dacron graft. Iliofemoral
      bypass using 6 mm Dacron grafts was performed in 10 German shepherd dogs. In
      accordance with preoperative randomization to individual animal legs, distal
      anastomoses were reconstructed using four different groups (A, B, C, and D),
      depending on the length of the arteriotomy: 3.0, 3.5, 4.0, and 4.5 times the
      internal diameter of the artery, respectively. The vessels were harvested 6
      months after the operation, and specimens were processed for histologic and
      transmission electron microscopic (TEM) studies. Quantitative analysis was
      performed to assess the extent of intimal hyperplasia at three zones (heel, toe,
      and midzone of the arterial bed) of the distal anastomosis. Sixteen arterial
      bypasses were included in this study. Both light and TEM studies revealed
      evidence of intimal hyperplasia in the four groups. Quantitative analysis showed
      a significant decrease in intimal hyperplasia with increasing the length of the
      anastomosis at the heel, toe, or midzone of the arterial bed. Mean (mum +/- SD)
      intimal hyperplasia of the three zones together was significantly higher in group
      A than group B (585 +/- 106 vs 423 +/- 8.6, p < .001) and in group B than group C
      (423 +/- 8.6 vs 202 +/- 15, p < .001). However, the difference between group C
      and group D (202 +/- 15 vs 162 +/- 8.6; p = .13) was statistically insignificant.
      The present study showed that the length of the anastomosis is one of the
      hemodynamic factors involved in the development of intimal hyperplasia.
      Anastomotic techniques that resulted in the least intimal hyperplasia were end to
      side, with length 4 or 4.5 times the internal diameter of the artery.

PMID- 20822720
TI  - Proteomics and pitfalls in the search for potential biomarkers of abdominal
      aortic aneurysms.
AB  - Proteomics is evolving as an important research technique in cardiovascular
      disease. We present exploratory research for a systemic biomarker of abdominal
      aortic aneurysm (AAA) in serum. Forty patients, 20 with large AAAs and 20 matched
      controls, were prospectively recruited. Serum was harvested, enriched, and mined
      for differential protein expression. Difference in gel electrophoresis using a
      two-dimensional platform, cyanine labeling, and Progenesis SameSpots software
      identified protein spots with significantly altered intensity. Liquid
      chromatography mass spectrometry aligned to the Seaquest protein database
      characterized proteins of interest, and 436 protein spots were demonstrated from
      the 20 processed gels. Thirteen spots of interest, demonstrating fold change (1.7
      4) between the two patient cohorts and consistent significant differential
      expression (analysis of variance, p </= .003), were picked for identification.
      Four of 13 spots were identified according to their tandem mass spectra. These
      were fragments of serum albumin, hemoglobin, and apolipoprotein C-II precursor.
      Identified spots represented proteins highly abundant in serum, not candidate
      biomarkers. Issues of variability surrounding serum harvest, processing,
      enrichment, and the challenge of identifying minimally expressed proteins
      currently limit this avenue of research. No proteins identified in this study had
      the biologic plausibility to represent a possible biomarker of aneurysmal
      disease. The tissue proteome may be a more rewarding approach for preliminary
      investigation of plausible biomarkers.

PMID- 20822721
TI  - Technical considerations for transabdominal aortic reconstruction with renal
      fusion and ectopia: case series.
AB  - Aortic diseases associated with renal anomalies can present special challenges
      during surgery of the abdominal aorta. The aim of this paper is evaluation of
      morbidity and definition of optimal management according to the clinical
      histories of 30 patients with horseshoe and ectopic kidneys who underwent
      surgical procedures on the abdominal aorta over a 20-year period. Twenty-two of
      them had horseshoe kidney and eight had ectopic kidney. Indications for surgery
      included aortic aneurysms in 25 patients and aortoiliac occlusive disease in 5.
      Preoperative diagnostics were performed in all cases by means of computed
      tomography and angiography (except in the cases with ruptures) associated with
      duplex ultrasonography. In patients with ectopic kidney a Carrel patch technique
      was used for the reimplantation of the renal arteries into the body of the
      bifurcated (four cases) or tubular (four cases) Dacron graft in five (62.5%)
      cases whereas aortorenal bypass with Dacron graft was obtained in three cases
      (37.5%). Sixteen patients from the horseshoe kidney group required renal
      revascularization (reimplantation using Carrel patch in 10 patients and
      aortorenal bypass using Dacron graft in 6 patients). Two patients, both with
      ruptured abdominal aortic aneurysms died after the operation. In other cases the
      average follow up period was 6.2 years (6 months to 17 years). In one case
      control, angiography after 6 months revealed an occluded left renal artery that
      was reimplanted by Carrel patch but without repercussions on the renal function.
      Aortic surgery in patients with renal anomalies can be safely performed without
      increased mortality.

PMID- 20822722
TI  - Hemodynamic effects of closure of residual arteriovenous fistulae during in situ
      graft procedures.
AB  - The objective was to study the intraoperative hemodynamic effects of closure of
      residual arteriovenous fistulae during in situ saphenous vein graft procedures.
      Data on 60 residual arteriovenous fistulae in nine patients (five men) with a
      median age of 74 years (range 64-83 years) with critical lower limb ischemia were
      obtained. Direct measurements of proximal and distal blood pressures in the graft
      were taken and simultaneous determinations of volume blood flow proximally and
      distally in the graft with ultrasound transit time technique before and after
      closure of residual fistulae were made. Closure of a fistula with blood flow
      around or below 100 mL/min did not increase distal outflow, whereas closure of
      fistulae with higher blood flow resulted in unpredictable changes in distal
      outflow. Only fistulae with a blood flow above approximately 100 mL/min may be of
      hemodynamic significance.

PMID- 20822723
TI  - Delirium after emergency/elective open and endovascular aortoiliac surgery at a
      surgical ward with a high-standard delirium care protocol.
AB  - Delirium is a common problem in elderly patients undergoing surgery. Standard
      delirium care is not available at all surgical wards. We determined the
      incidence, risk factors, and outcomes of postoperative delirium among patients
      undergoing elective/emergency aortoiliac surgery at a surgical ward with high
      standard delirium care. A prospective descriptive survey in 107 patients was
      conducted. High-standard delirium care was given to patients above age 65,
      consisting of an extended focus on risk factors and intensive screening. The
      Delirium Observation Scale was used as a screening instrument for delirium.
      Patients were classified as having delirium if they met the DSM-IV criteria. The
      overall incidence of delirium was 23%. The incidence was 14% after elective
      surgery. Delirium occurred in 59% after emergency surgery and more often after
      open than after endovascular aneurysm repair (p < .01). Delirium was associated
      with age (p < .01) and emergency surgery (p = .01) and is an important and
      frequent complication after aortoiliac surgery.

PMID- 20822724
TI  - Repeat endovascular exclusion for distal tear after treatment of primary aortic
      dissection by endovascular exclusion.
AB  - An obese, hypertensive, 70-year-old man was found to have an extensive chronic
      Stanford type B aortic dissection. The dissection was treated by placement of a
      stent graft. One year later, he developed a small protrusion of the intimal flap
      at the distal end of the stent graft that gradually enlarged, until 4 years after
      the procedure, it had become disrupted, and angiography showed contrast medium
      entering the false lumen. A second stent graft was successfully placed, and
      imaging 2 years later indicated no recurrence of the tear, endoleak, or
      malperfusion of the aortic arch vessels.

PMID- 20822725
TI  - Duplication of the superficial femoral artery.
AB  - A computed tomographic angiogram for pseudoaneurysm after previous puncture in
      the groin showed duplication of the superficial femoral artery in a 52-year-old
      man without symptoms or signs of arterial insufficiency. It is doubtful whether
      this very rare anatomic variant has clinical relevance, but it should be known by
      vascular specialists.

PMID- 20822726
TI  - Surgical treatment of symptomatic coiling or kinking internal carotid artery.
AB  - Coiling of the artery is a rare morphologic entity most frequently described in
      the internal carotid artery. Herein we present two cases with symptomatic kinked
      internal carotid artery: one suffering from paresthesia of the right arm and
      speech disturbances and the other suffering from weakness of the left half of the
      body and speech disturbances. Both patients were treated surgically. None of the
      patients experienced any peri- or postoperative complications.

PMID- 20822727
TI  - Down syndrome: a risk factor for mycotic aneurysm?
AB  - Down syndrome, or trisomy 21, has a characteristic constellation of clinical
      findings, including various congenital heart defects. We report a case of an
      adult male with Down syndrome who presented with a 3-week history of lower limb
      pain and swelling, attributed to cellulitis. Clinical and angiographic evaluation
      identified a below-knee mycotic pseudoaneurysm secondary to infective
      endocarditis. Surgical aneurysmal repair and revascularization were performed.
      Various management options are outlined in this report.

PMID- 20822728
TI  - Recurrent aortic aneurysms in Behcet disease.
AB  - The following is a case of a 22-year-old male with recurrent thoracic aneurysms
      with several constitutional symptoms, including gastrointestinal discomfort,
      irritable bowel syndrome, lactose intolerance, and a 2-week history of severe
      lower back pain. The patient underwent an initial thoracoabdominal repair of a
      visceral aneurysm followed by endovascular repair of a recurrent thoracic
      pseudoaneurysm. The etiology of the visceral aneurysm was initially hypothesized
      to be mycotic; however, further information revealed signs and symptoms
      consistent with the diagnostic criteria for Behcet disease (BD). We suggest that
      BD be considered in younger patients who present with an aortic aneurysm.
      Although open repair is the traditional approach for arterial lesions in BD, the
      role for endovascular intervention should be considered as it represents a
      surgical repair with a significant reduction in morbidity.

PMID- 20822729
TI  - Rupture of an abdominal aortic aneurysm following nonaccidental blunt abdominal
      trauma.
AB  - A 78-year-old woman presented to our trauma center with an initial, erroneous
      history of a ground-level fall. Further investigation revealed that the patient
      had been assaulted by her husband immediately prior to presentation. The initial
      abdominal examination was benign, and the patient was hemodynamically stable. The
      patient was found to have a large subdural hematoma (SDH). Following open
      evacuation of the SDH, the patient developed ongoing hemodynamic instability.
      Further evaluation with computed tomography of the abdomen and pelvis uncovered
      the diagnosis of a 6 cm abdominal aortic aneurysm (AAA) with a large
      retroperitoneal hematoma. The patient underwent emergent repair of the ruptured
      AAA. There were no other significant intra-abdominal injuries, and the patient
      had an uneventful recovery. This case highlights the need for thorough evaluation
      of the trauma patient and recognition of the possibility of coexistent AAA in the
      elderly trauma patient. We believe that this is the first reported case of a
      ruptured AAA following nonaccidental blunt abdominal trauma.

PMID- 20822730
TI  - Epithelioid hemangioma of the ulnar artery.
AB  - This case report describes a rare vascular tumor (epithelioid hemangioma) in the
      ulnar artery of a young male patient, treated by excision and bypass grafting.

PMID- 20822732
TI  - Micro-simulation of a smallpox outbreak using official register data.
AB  - To explore the efficacy of four vaccine-based policy strategies (ring
      vaccination, targeted vaccination, mass vaccination, and pre-vaccination of
      healthcare personnel combined with ring vaccination) for controlling smallpox
      outbreaks in Sweden, disease transmission on a spatially explicit social network
      was simulated. The mixing network was formed from high-coverage official register
      data of the entire Swedish population, building on the Swedish Total Population
      Register, the Swedish Employment Register, and the Geographic Database of Sweden.
      The largest reduction measured in the number of infections was achieved when
      combining ring vaccination with a pre-vaccination of healthcare personnel. In
      terms of per dose effectiveness, ring vaccination was by far the most effective
      strategy. The results can to some extent be adapted to other diseases and
      environments, including other countries, and the methods used can be analysed in
      their own right.

PMID- 20822733
TI  - Antibiotics for the common cold: expectations of Germany's general population.
AB  - Physicians mention patients' expectations as a reason for prescribing antibiotics
      for common (viral) upper respiratory tract infections despite clinical evidence
      against their use and the physicians' better judgement. We aimed to assess the
      prevalence of such expectations and factors of influence (knowledge and
      attitudes) in Germany's general population. In November 2008, 1,778 persons
      registered with a large market research company were invited to complete an
      online questionnaire on expectations concerning prescription of antibiotics and
      on knowledge and attitudes regarding the effectiveness and use of antibiotics for
      upper respiratory tract infections. A total of 1,076 persons aged 15-78 years
      participated (response: 61%), of whom 91.8% reported using antibiotics 'only if
      absolutely necessary'. Prescription of antibiotics was expected by 113 (10.5%) of
      the 1,076 respondents for the common cold and by 997 (92.7%) for pneumonia. In a
      logistic regression analysis, predictors for expecting a prescription for
      antibiotics for the common cold included the following opinions: 'common cold or
      flu can effectively be treated with antibiotics' (prevalence: 37.6%; odds ratio
      (OR): 9.6; 95% confidence interval (CI): 3.8 to 24.3) and 'antibiotics should be
      taken when having a sore throat to prevent more serious illness' (prevalence
      8.6%; OR: 7.6; 95% CI: 3.9 to 14.5). Among those expecting a prescription
      (n=113), 80 (71%) reported that they would trust their physician when he or she
      deems a prescription unnecessary; a further eight (7%) would be unsatisfied, but
      would accept the decision. Our results suggest that only a minority expects
      antibiotics for the treatment of cold symptoms. Physicians should be educated
      that their decisions not to prescribe antibiotics for the common cold, even when
      against patients' expectations, are apparently accepted by the majority.

PMID- 20822734
TI  - Spotlight on measles 2010: excretion of vaccine strain measles virus in urine and
      pharyngeal secretions of a child with vaccine associated febrile rash illness,
      Croatia, March 2010.
AB  - We describe excretion of measles vaccine strain Schwarz in a child who developed
      a febrile rash illness eight days after primary immunisation against measles,
      mumps and rubella. Throat swabs and urine specimens were collected on the fifth
      and sixth day of illness, respectively. Genotyping demonstrated measles vaccine
      strain Schwarz (genotype A). If measles and rubella were not under enhanced
      surveillance in Croatia, the case would have been either misreported as rubella
      or not recognised at all.

PMID- 20822735
TI  - Pertussis outbreak in northwest Ireland, January - June 2010.
AB  - We report a community pertussis outbreak that occurred in a small town located in
      the northwest of Ireland. Epidemiological investigations suggest that waning
      immunity and the absence of a booster dose during the second year of life could
      have contributed to the outbreak. The report also highlights the need to
      reinforce the surveillance of pertussis in Ireland and especially to improve the
      clinical and laboratory diagnosis of cases.

PMID- 20822736
TI  - ESCAIDE 2010 - an opportunity for sharing knowledge, building capacity and
      strengthening networks.

PMID- 20822737
TI  - [Management of quality in an Intensive Care Unit: implementation of ISO 9001:2008
      international standard].
AB  - The Quality Management Systems make it possible to prioritize actions to maintain
      the safety and efficacy of health technologies. The Intensive Care Unit of our
      hospital has implemented a quality management plan, which has obtained
      accreditation as "Service Certificate that manages its activities according to
      UNE-EN ISO 9001:2008" standard. With the application of quality management
      system, it has been possible to detect the needs that the Service can cover in
      order to obtain the satisfaction of the patient, relative or health personnel of
      the other services of the hospital, to improve communications inside and outside
      of service, to secure greater understanding of the processes of the organization
      and control of risk, to delimit responsibilities clearly to all the personnel, to
      make better use of the time and resources and, finally, to improve the motivation
      of the personnel.

PMID- 20822738
TI  - Intense implementation of a strict insulin infusion protocol does not guarantee
      postoperative glycemic control.
AB  - BACKGROUND: The Surgical Care Improvement Project (SCIP) has benchmarked 6:00 AM
      blood sugars on postoperative days (PODs) 1 and 2 at <200 mg/dL as an indicator
      of overall glycemic control (GC) in postoperative cardiac surgery patients.
      However, even in demonstration hospitals that publicly report for incentive
      payments, only 10% are compliant with this benchmark. The objectives of this
      study were to validate that the SCIP indicator correlates with overall GC, and
      relate the intensity of implementation of an insulin infusion protocol (IIP)
      (goal, blood sugar 100 to 140 mg/dL) to effective GC. STUDY DESIGN: All
      postoperative cardiac surgery patients for 12 consecutive months on the IIP were
      divided into 2 groups: group 1 included patients who were SCIP compliant (n =
      98), and group 2 were patients who were not SCIP compliant (n = 10). For each
      patient, we determined average blood sugar, duration of hyperglycemia (percent of
      time with blood sugar >200mg/dL), and intensity of implementation of the IIP,
      defined as (number of blood sugar checks/hours on IIP), with 0.5 = minimum
      intensity of implementation dictated by the IIP, ie, an insulin adjustment every
      2 hours. RESULTS: The average blood sugar for each of the 110 patients was no
      different than the SCIP 6:00 AM blood sugar: 146 versus 154 mg/dL, p = 0.18. SCIP
      noncompliance correlated with more intense implementation of the IIP, 0.72 +/-
      0.03 versus 0.83 +/- 0.06 blood sugar checks/hour. CONCLUSIONS: The SCIP 6:00 AM
      blood sugar metric does correlate with average blood sugar on POD 1. Compliance
      with SCIP 6:00 AM blood sugar measurement is a valid surrogate for GC, though
      duration of hyperglycemia was still 14% in the compliant group. Use of an IIP
      does not guarantee GC, despite increased intensity of its application. Even
      intense use of an IIP may be ineffective when it fails to account for patient
      risk factors for hyperglycemia.

PMID- 20822739
TI  - A fast-track recovery protocol improves outcomes in elective laparoscopic
      colectomy for diverticulitis.
AB  - BACKGROUND: Fast-track (FT) postoperative protocols have been shown to be highly
      beneficial in open colectomy. Some have questioned the necessity of an FT
      protocol in the setting of laparoscopic colectomy because hospital stays are
      short and morbidity is low compared with open surgery. We set out to determine
      whether an FT protocol has any utility in the setting of elective laparoscopic
      colectomy. STUDY DESIGN: A retrospective review was conducted on a cohort of 334
      patients who underwent elective laparoscopic sigmoid resection for diverticulitis
      from 1998 to 2008, at Mayo Clinic, a tertiary care center in Rochester, MN. There
      were 235 patients who were managed with traditional postoperative care, and 99
      who were managed with an FT protocol initiated in 2006. The main outcomes
      measures were time to soft diet, length of stay, overall morbidity, and
      readmission rate. RESULTS: Times to soft diet (mean 2.3 vs 3.6 days), and first
      bowel movement (mean 2.6 vs 3.5 days) were shorter in the FT group (p < 0.001).
      The median lengths of stay were 3 days (interquartile range 3 to 4 days) and 5
      days (interquartile range 4 to 6 days) for the FT and non-FT groups, respectively
      (p < 0.001). Morbidity was significantly lower in the FT group compared with the
      non-FT group (15.2% vs 25.5%, p < 0.03). The 30-day readmission rate was 2.9% for
      the FT group and 7.6% for the non-FT group (p = NS). There were no deaths in
      either group. CONCLUSIONS: Even in patients undergoing laparoscopic colectomy, FT
      protocols further improve the speed of gastrointestinal recovery, shorten the
      length of stay, and decrease morbidity.

PMID- 20822740
TI  - Surgical management of acute right lower-quadrant pain in pregnancy: a
      prospective cohort study.
AB  - BACKGROUND: The etiology of right lower-quadrant pain in pregnant patients is a
      challenge in diagnosis. We discuss the surgical issues among pregnant patients
      with right lower-quadrant pain and demonstrate the method to diagnosis. STUDY
      DESIGN: This was a prospective cohort study with enrollment during 2 years.
      Pregnant patients presenting with acute right lower-quadrant abdominal pain and
      requiring surgical consult were included. Demographics, gestational age,
      symptoms, workup, operative results, and pathology were recorded. RESULTS: One
      hundred patients were enrolled, 38 had nonspecific abdominal pain, 15 of whom
      were admitted. There were no differences in temperature, leukocyte count, and
      neutrophil shift among the admitted and nonadmitted patients. Forty-one patients
      underwent surgery and had a substantially higher gestational age, leukocyte
      count, and neutrophil shift than those who did not. Ultrasound was performed
      considerably more often on first-trimester patients (81.6%) compared with second-
      (58.1%) and third-trimester (57.9%) patients, and CT scan was used considerably
      less in the first trimester compared with the second and third trimesters, and
      considerably less than ultrasound for the first trimester. Sensitivity of
      ultrasound for appendicitis was inversely correlated to fetal gestational age,
      and CT scan retained high sensitivity and specificity throughout pregnancy.
      CONCLUSIONS: This is one of the first prospective studies assessing diagnoses and
      workup of pregnant patients with right lower-quadrant pain. We recommend
      abdominal ultrasound be the first imaging modality for patients for whom surgical
      consultation is necessary, thereby determining if the pathology is obstetric. If
      inconclusive, a CT scan is necessary to guide treatment.

PMID- 20822741
TI  - Perioperative management of hepatic resection toward zero mortality and
      morbidity: analysis of 793 consecutive cases in a single institution.
AB  - BACKGROUND: The mortality rates associated with hepatectomy are still not zero.
      Our aim was to define the risk factors for complications and to evaluate our
      perioperative management. STUDY DESIGN: Between 2001 and 2008, 793 consecutive
      patients (547 men and 246 women; mean age +/- SD, 56.1 +/- 14.9 years) underwent
      hepatectomy without gastrointestinal resection and choledocojejunostomy at our
      center. Of these patients, 354 (44.6%) were positive for the hepatitis B virus
      surface antigen and/or the hepatitis C virus antibody. We categorized 783 (98.7%)
      patients as Child-Pugh class A. Major resection (sectionectomy, hemihepatectomy,
      and extended hemihepatectomy), was performed in 535 patients (67.5%) and re
      resection in 81 patients (10.2%). RESULTS: The median operative time was 345.5
      minutes and median blood loss was 360 mL. The rate of red blood cell transfusion
      was 6.8%. The morbidity rate was 15.6%. Reoperations were performed in 19
      patients (2.4%). The mean postoperative hospital stay was 18.4 +/- 10.4 days. The
      in-hospital mortality rate was 0.1% (1 of 793 patients; caused by hepatic
      failure). The independent relative risk for morbidity was influenced by an
      operative time of more than 360 minutes, blood loss of more than 400 mL, and
      serum albumin levels of less than 3.5 g/dL, as determined using multivariate
      logistic regression analysis. CONCLUSIONS: Shorter operative times and reduced
      blood loss were obtained by improving the surgical technique and using new
      surgical devices and intraoperative management, including anesthesia.
      Additionally, decision making using our algorithm and perioperative management
      according to CDC guidelines reduced the morbidity and mortality associated with
      hepatectomy.

PMID- 20822742
TI  - Plugoma: CT findings after prosthetic plug inguinal hernia repairs.
AB  - BACKGROUND: Unrecognized CT findings of a prosthetic plug used in inguinal hernia
      repair can lead to incorrect diagnosis or unnecessary workup of a patient. The
      objective of this study is to review the expected CT findings present in patients
      with a history of plug repair. STUDY DESIGN: Retrospective cohort study
      retrieving clinical and image data from a single-institution database. Patients
      who underwent prosthetic plug hernia repair during a 5-year period at our
      institution had their records queried for subsequent abdominal CT scans. These CT
      scans were reviewed by 2 radiologists for findings referable to the hernia
      repair. RESULTS: Five-hundred and sixty-four consecutive patients underwent
      prosthetic plug hernia repair during a 5-year period. Fifty-one patients who had
      had 55 surgical procedures had subsequent CT scans, none in the early
      postoperative period. Readers identified 100% of the plugs, 68% of which were
      described as round or oval in shape. All the plugs were in close proximity to the
      inferior epigastric artery and were of low density on CT images. Surgical scar
      was identifiable in 87% of patients. Thirty-two patients (63%) had a second CT
      scan, demonstrating no change in size and location of the plugoma. CONCLUSIONS: A
      prosthetic mesh plug is easily seen on CT images, typically appearing as a smooth
      round or oval hypodense mass close to the inferior epigastric artery, deep to a
      surgical scar, and stable over time. It can usually be distinguished from
      pathologic findings. It is important that the radiologist be familiar with the
      patient's surgical history when interpreting these images.

PMID- 20822743
TI  - Does routine use of ultrasound result in additional thyroid procedures in
      patients with primary hyperparathyroidism?
AB  - BACKGROUND: Minimally invasive parathyroidectomy for primary hyperparathyroidism
      depends on accurate preoperative imaging. Cervical ultrasound is commonly used to
      localize parathyroid adenomas, but can lead to discovery of concomitant thyroid
      gland pathology requiring modification of the operative approach. How the
      identification of incidental thyroid lesions affects patient management is
      unclear. STUDY DESIGN: A prospective database of patients undergoing
      parathyroidectomy was analyzed for thyroid pathology discovered by ultrasound.
      Lesions were biopsied if indicated, and operative management was adjusted
      accordingly. Clinical data were correlated with operative decision-making.
      RESULTS: Between July 2002 and November 2009, 310 patients with primary
      hyperparathyroidism underwent ultrasound. Concomitant thyroid pathology was noted
      in 89 (29%) patients. Thirty-seven patients (42% of pathology) underwent fine
      needle aspiration of a thyroid nodule. Thirteen patients (4% of all patients)
      underwent a thyroid operation not related to parathyroid disease: 9 thyroid
      lobectomies for presumably benign nodules and 4 total thyroidectomies for
      malignancy. Two were for confirmed papillary thyroid cancer, and the other 2 were
      for an indeterminate biopsy that later proved to be papillary thyroid cancer. One
      lobectomy discovered microscopic papillary thyroid cancer independent of the
      biopsied nodule. In total, 5 (2% of all patients) malignancies were discovered.
      CONCLUSIONS: Twenty-nine percent of patients with primary hyperparathyroidism had
      concomitant thyroid pathology on ultrasound. Forty-two percent of these patients
      underwent biopsy, and 2% had malignant pathology. Routine use of ultrasound in
      patients with primary hyperparathyroidism leads to discovery of unrecognized
      thyroid pathology and cancer.

PMID- 20822744
TI  - Second impact syndrome: concussion and second injury brain complications.

PMID- 20822745
TI  - Living donor hepatectomies with procedures to prevent biliary complications.
AB  - BACKGROUND: Biliary complications in donor hepatectomies are still common, and
      occur in approximately 5% of the procedures. STUDY DESIGN: To evaluate the
      usefulness of the management and surgical procedures to prevent the biliary
      complications in donor hepatectomies, a total of 343 donors were retrospectively
      studied. The clinical and surgical parameters of the donors and the postoperative
      biliary complications were evaluated. RESULTS: Fourteen donors had biliary
      complication (BC) during the follow-up period (4.1%). Donors were divided into 2
      groups; donors without BC (non-BC group; n = 329) and donors with BC (BC group; n
      = 14). Mean peak level of total bilirubin, mean duration of hospital stay after
      surgery, and medical cost in the BC group were significantly higher than in the
      non-BC group (p < 0.01). As improved procedures to prevent the BC were
      established at 2005, including the use of a real-time cholangiography by the C
      arm, a minimized dissection of the hepatic vessels, the meticulous closure of the
      bile duct, and/or the use of Pringle maneuver during the parenchymal transection,
      the donors were divided into 2 groups before and after these establishments (the
      early period, n = 173; the later period, n = 170). Refinements in the management
      and surgical procedures reduced the occurrence of biliary complications from 6.4%
      during the early period to 1.8% during the later period (p < 0.01), and no
      biliary complications in the last 69 consecutive donors were observed.
      CONCLUSIONS: Technical refinements described in this study might be useful to
      prevent the occurrence of biliary complications in a donor hepatectomy. It is
      particularly important to preserve the blood supply for the biliary tract of both
      the graft and the remnant liver.

PMID- 20822746
TI  - Recent changes in our scientific journal.

PMID- 20822747
TI  - Surgical-site infections and surgery of the salivary glands.
AB  - OBJECTIVES: To determine the surgical-site infection (SSI) incidence rate
      targeted on salivary gland surgery over a 2-year period (from January 2007 to
      December 2008). Then identify any risk factors associated with SSI in all the
      patients operated with no antibiotic prophylaxis in accordance with French
      Anesthesiology Society guidelines. POPULATION AND METHODS: Ninety-three patients
      were operated during the standard SSI surveillance period. A case-control (one
      case for five controls) study was then conducted aiming to identify risk factors.
      RESULTS: The SSI incidence rate was 9.7%. The case-control study failed to
      identify any relevant risk factor with univariate analysis. CONCLUSION: As no
      risk factors could be identified, we suggest that surgical antibioprophylaxis
      could be relevant in salivary glands surgery and should be evaluated in this
      setting.

PMID- 20822748
TI  - Pendred syndrome in Tunisia.
AB  - OBJECTIVES: We report a clinical and genetic study of three consanguineous
      Tunisian families affected by Pendred syndrome. PATIENTS AND METHODS: Three
      families from the south of Tunisia were identified as affected by Pendred
      syndrome. The patients and their families underwent ENT and general examination
      and audiovestibular and radiological tests. Molecular DNA analysis was performed
      by the Sfax Human Molecular Genetics Department. RESULTS: Forty-three patients
      (mean age: 21 years [2-60 years]) were affected. Tonal audiometry showed
      bilateral sensorineural hearing loss in 87.5% of cases, and mixed hearing loss in
      12.5% with bilateral high frequency sensorineural hearing loss and conductive
      hearing loss at lower frequencies. Deafness was severe in 21% and profound in 79%
      of cases. Thyroid goiter was found in 46.5% of cases. Inner ear CT scan found
      enlarged bilateral vestibular aqueducts in all cases. Hormone analysis was normal
      and perchlorate test negative in all cases. A single Pendred syndrome (PDS) gene
      mutation, L445W, was found. DISCUSSION: Pendred syndrome is the most frequent
      congenital deafness syndrome. It is characterized by great intrafamilial
      phenotype variability.

PMID- 20822749
TI  - Middle ear implant for mixed hearing loss with malformation in a 9-year-old
      child.
AB  - OBJECTIVE: The aim was to report the results of the first case in France of
      pediatric auditory rehabilitation with a middle ear implant and to discuss the
      putative indications with this new therapeutic option in children. PATIENT AND
      METHODS: A prospective study over 18 months on clinical and audiometric results
      after a middle ear implantation with a Vibrant Med-El(R) implant in a 9-year-old
      child with mixed hearing loss. RESULTS: Postoperative unaided pure tone
      audiometry (PTA) was unchanged by the surgical procedure. After 18 months of
      implant use, the mean PTA loss in free-field warble tone audiometry was 33.75 dB
      and the intelligibility threshold was 30 dB. After 18 months of follow-up, the
      intelligibility threshold was improved by 25 dB in comparison with the
      preoperative results with two hearing aids. The implant worked perfectly well and
      the child did not show any complication during this period. CONCLUSION: The
      reliability of the implant and the quality of the auditory results obtained in
      this case and in a limited number of cases in the world make the Vibrant Med
      El(R) a new therapeutic option in hearing loss in children with bilateral
      auricular atresia.

PMID- 20822750
TI  - Osteoma of the internal auditory canal.
AB  - OBJECTIVE: Osteoma occurs almost exclusively in the head and neck region, only
      rarely developing into the internal auditory canal. We report an incidental
      finding of a case in the radiological evaluation of a patient with left
      hemifacial spasm. PATIENTS AND METHODS: A 79-year-old woman consulted for left
      hemifacial spasm associated with left anacusis. Symptoms occurred up to 30 years
      prior to the first radiological investigations. Computed tomographic (CT) and
      magnetic resonance (MRI) images were taken. RESULTS: MRI demonstrated a left
      internal auditory canal lesion with spontaneous hypointense signal on T1- and T2
      weighted images. CT showed the lesion as a typically dense and opaque osteoma. It
      measured 0.6 cm in maximum size. No surgery was performed because of the slow
      growing features of the lesion. Clinical monitoring was recommended. CONCLUSION:
      Osteomas are diagnosed incidentally in asymptomatic patients. Our case was
      symptomatic and raised the question of surgical management. This article
      discusses the presentation and management associated with this exceptional
      osteoma location.

PMID- 20822751
TI  - Sclerosing polycystic adenosis of the parotid gland: diagnosis and management.
AB  - OBJECTIVE: To describe diagnostic and therapeutic management of a rare parotid
      lesion: sclerosing polycystic adenosis. PATIENT AND METHOD: We report a case of
      persistent right intraparotid tumefaction. RESULTS: A 68-year-old man was
      referred with a right parotid nodule of 2 years' evolution. Cytology diagnosed
      pleomorphic adenoma, verified on MRI. Conservative subtotal parotidectomy
      diagnosed sclerosing polycystic adenosis. Over 1 year's regular follow-up, there
      were no signs of local recurrence. CONCLUSION: Sclerosing polycystic adenosis of
      the parotid gland is a rare and recently described entity presenting several
      analogies to the much more frequent cystic mastitis. Although benign and well
      delimited, it requires complete exeresis of the parotid, due to a non-negligible
      risk of recurrence.

PMID- 20822752
TI  - Laryngotracheal separation in neonatal brainstem dysfunction.
AB  - INTRODUCTION: Neonatal brainstem dysfunction (NBD) associates four symptoms of
      variable presence and intensity: suction-swallowing dysfunction, abnormal
      laryngeal sensitivity and motility, gastroesophageal reflux, and cardiac vagal
      overactivity. MATERIALS AND METHODS: We report three cases of severe NBD with
      chronic aspiration which required surgical management. Successive failures and
      clinical deterioration led us to perform laryngotracheal separation. The surgical
      procedure consisted in suturing the distal segment of the trachea to the cervical
      skin after complete closure of the larynx. RESULTS: After surgery, these children
      did not present any pulmonary infection and were allowed oral nutrition. However,
      oral communication was no longer possible. Although it is a theoretically
      reversible procedure, the decision is ethically difficult in children free of
      mental deficiency, because of the vocal loss and the unpredictable NBD outcome.
      CONCLUSION: Laryngotracheal separation may be recommended after multidisciplinary
      decision for severe chronic aspiration in the particular case of children
      presenting with NBD.

PMID- 20822753
TI  - Sinonasal mucormycosis: case report.
AB  - OBJECTIVES: To present and discuss the case of a diabetic patient admitted with
      acidoketotic coma, with inner canthus tumefaction due to mucormycosis. CASE
      STUDY: A 38-year-old diabetic man was admitted with acidoketotic coma and poor
      general health status. Clinical examination found right inner canthus tumefaction
      and mucopurulent rhinorrhea. Endoscopy of the nasal fossae found medial meatus
      sphaceluses. Sinus CT scan found a bilateral ethmoid infiltrating and osteolytic
      infectious process. Emergency endoscopic bilateral ethmoidectomy was performed.
      Mucormycosis was diagnosed, and liposomal amphotericin B was administered
      intravenously for 1 month then replaced by posaconazole. The patient was followed
      up monthly; the antifungal treatment was terminated after 8 months, the disease
      appearing to have resolved. COMMENTS AND CONCLUSION: Mucormycosis is one of the
      most rapidly fatal fungal infections. Facial and cerebral CT scan is essential
      and is systematically abnormal in case of sinonasal mucormycosis. Emergency
      multidisciplinary treatment should address the diabetes and include rapid
      surgical debridement and effective antifungal medication. The reference
      antifungal is amphotericin B, to be administered at maximal dose (3 to 5 mg/kg
      per day). Posaconazole, available in Europe since July 2005, proved successful in
      the present case.

PMID- 20822754
TI  - Fetal rhabdomyoma of the infratemporal fossa in children.
AB  - INTRODUCTION: Fetal rhabdomyomas are very rare benign tumors with infrequent head
      and neck involvement. We present the first report of a case of a 3-year-old child
      with an infratemporal fossa location. MATERIAL AND METHODS: Case study.
      DISCUSSION: Given the volume of the tumor and its difficult-to-access location,
      medical treatment associating methotrexate and Velbe(R) was proposed, but was not
      effective on the tumor volume after four courses. Surgical intervention via a
      combined intraoral and preauricular temporal approach allowed monoblock excision.
      There were no postoperative complications. CONCLUSION: Medical treatment was
      unsuccessful. Surgical excision controlled the lesion with no recurrence since
      surgery. The main differential diagnosis is rhabdomyosarcoma.

PMID- 20822755
TI  - Image-guided sinus surgery.
AB  - Image-guided surgery (IGS) is extremely useful for anatomic location in at-risk
      sinus surgery: extensive inflammatory disease, sinus cavity revision, and frontal
      sinus, posterior ethmoid, sphenoid or nasosinal tumor surgery. There are two
      systems on the market, based on electromagnetic and infrared detection,
      respectively; optimal functioning depends on calibration. IGS is only a location
      aid, complementary to and not a substitute for endoscopy. It enables the
      experienced endonasal surgeon to check the endoscopic location at any time, and
      provides appreciable "psychological" comfort in what are difficult and sometimes
      stressful operations, the limits of which are being forever pushed back.

PMID- 20822756
TI  - Role of positron emission tomography (PET) in head and neck cancer.
AB  - F-18 fluorodeoxyglucose positron emission tomography is now part of the initial
      stage III and IV cancer work-up and each time that metastasis or the presence of
      a second cancer is suspected that may contraindicate major surgery. Similarly,
      this exam should be undertaken when the conventional work-up is negative but
      there is isolated metastatic adenopathy. In therapeutic follow-up, a 3- or 4
      month delay must be respected to prevent false-positive exams caused by
      inflammation. Although FDG-PET seems very promising in determining target volumes
      in radiotherapy, its implementation raises a number of problems that can only be
      resolved through the collaboration of all of the different specialists.

PMID- 20822757
TI  - Glioblastoma multiforme mimicking a frontal abscess after surgery for a large
      vestibular schwannoma.
AB  - OBJECTIVES: Routine vestibular schwannoma surgery can result in serious and
      potentially lethal infectious complications. A high degree of vigilance is
      necessary to diagnose these uncommon infections and in case of postoperative
      neurological symptoms, brain magnetic resonance imaging should be performed to
      eliminate a brain abscess. In some cases, the final diagnosis is not the expected
      one. CLINICAL PRESENTATION: A 39-year-old man presented three months
      postoperatively after a vestibular schwannoma removal by translabyrinthin
      approach with a rapid and progressive history of headaches, confusion, and left
      hemi paresis with fever. The brain CT and MRI were in favour of a delayed
      postoperative frontal abscess. TECHNIQUE: A biopsy under stereotactic guidance
      was performed. Histopathologic examination revealed WHO grade 4 glioblastoma
      multiforme. CONCLUSION: Symptoms and signs of glioblastoma multiforme are
      congruent with brain abscess. Its rapid evolution, the normality of the first
      magnetic resonance imaging, and its radiological aspect made it a differential
      diagnosis of a postoperative brain abscess and should be systematically
      researched.

PMID- 20822758
TI  - Surgical repair of labial defect.
AB  - The main cause of labial defect is carcinological, in 90% of cases involving the
      lower lip. Reconstruction for labial defect is a therapeutic challenge imposing
      two main requirements: to achieve good esthetic quality, and to conserve labial
      function. Steps of defect analysis is proposed. Very numerous techniques have
      been described that are not exhaustively explained in this surgical review. Thus,
      the authors suggest reliable, reproducible solutions that should enable the
      surgeon to deal with most of the labial defect situations encountered in
      practice, based on consensual indications. Node involvement and alternatives to
      surgery, such as X-ray therapy, also fall outside the field of the present
      article.

PMID- 20822759
TI  - Surgical treatment of large vestibular schwannomas (stages III and IV).
AB  - OBJECTIVE: Study the results of surgical treatment of large vestibular
      schwannomas. MATERIAL AND METHODS: Between January 1995 and December 2005, 87
      stage III and IV unilateral vestibular schwannomas (Koos classification) were
      operated. RESULTS: The approach used was for the most part translabyrinthine.
      Nine patients were operated in two phases. Tumor exeresis was total in 79% of the
      cases, nearly total in 17%, and subtotal in 3.6%. Good facial function was
      preserved in 63% of the patients. Mortality was zero. Tumor control after a mean
      follow-up of 45 months was 86%. CONCLUSIONS: Surgery for large vestibular
      schwannomas should have a 0% mortality rate and low morbidity. Otoneurosurgical
      collaboration, with a preference for the translabyrinthine approach, with surgery
      undertaken in several phases if need be, provides maximum safety and good
      functional results as well as an acceptable residual tumor rate.

PMID- 20822760
TI  - Sinonasal mucosal melanomas.
AB  - OBJECTIVES: Sinonasal mucosal melanomas account for approximately 1% of all
      melanomas. These tumors are particularly aggressive, with a recurrence rate
      between 37 and 54% and a 5-year survival rate between 20 and 46%. Metastases are
      frequent. The main objective of this study was to analyze all of our cases of
      sinonasal mucosal melanomas and determine any prognostic factors. PATIENTS AND
      METHODS: All our cases of sinonasal mucosal melanoma over a period of 10 years
      were included. Ten cases were analyzed. The mean age was 71 years (range: 61-85
      years) for seven women and three men. The clinical, radiological,
      anatomopathological, and surgical data as well as the characteristics of disease
      progression were analyzed. These data were compared to those reported in the
      literature. RESULTS: The mean follow-up was 36.3 months (range: 2-96 months). The
      5-year overall survival was 40%. Seven patients developed local recurrences after
      a mean follow-up of 16 months (range: 2-27 months) with associated metastases in
      three cases. Analysis of the prognostic factors showed that tumors classified as
      T1 and limited to the nasal fossae had a better prognosis. CONCLUSION: Sinonasal
      mucosal melanomas are rare tumors with a high mortality rate. Treatment of these
      tumors requires extensive surgical treatment associated with external
      radiotherapy.

PMID- 20822761
TI  - Coblation turbinate reduction in childhood allergic rhinitis.
AB  - INTRODUCTION: Nasal obstruction is the allergic rhinitis symptom least amenable
      to medical treatment, and inferior turbinectomy may be required. Coblation is a
      minimally invasive technique that is effective in obstruction secondary to
      inferior turbinate hypertrophy. The present study assessed efficacy in children
      presenting with obstructive allergic rhinitis after failure of medical
      management. PATIENT AND METHODS: This prospective study included nine children
      with allergic rhinitis. Coblation was performed after assessment of rhinitis.
      Obstruction was assessed on rhinomanometry and a visual analog scale; other
      rhinologic functional signs were assessed on interview, and functional impact was
      assessed on the PRQLQ quality of life questionnaire. RESULTS: After the
      procedure, all nine children showed reduced nasal obstruction and improved
      rhinologic function signs, confirmed by the favorable evolution of PRQLQ scores.
      CONCLUSIONS: The study demonstrated the interest of coblation in controlling
      nasal obstruction in children with allergic rhinitis refractory to medical
      treatment, with conserved nasal function. Larger-scale studies with longer follow
      up will be needed to confirm these results.

PMID- 20822762
TI  - Hypopharyngeal amyloidosis: A case report.
AB  - Hypopharyngeal amyloidosis is rare. Management depends on etiology. We report a
      case of hypopharyngeal amyloidosis and review the characteristics of this
      exceptional pathology. A 60-year-old woman with a history of diabetes and chronic
      cervicalgia consulted for dysphagia and deteriorated general health status, which
      had been evolving for 2 months. Clinical examination found two ulcerations of the
      lateral edge of the tongue and right pyriform sinus salivary stasis. Panendoscopy
      found regular swelling of the posterior wall of the hypopharynx and cervical
      esophagus. The pyriform sinuses and larynx were normal. Cervical CT and MRI
      showed thickening of the posterior wall of the hypopharynx. Biopsy found
      amorphous acellular eosinophil interstitial deposits, shown to be amyloid on
      Congo red staining, leading to a diagnosis of amyloidosis. Etiological assessment
      pointed to myeloma. The patient was managed by chemotherapy associating melphalan
      and prednisone. Evolution at 12 months' follow-up was good. Localized amyloidosis
      is a rare lesion of the superior aerodigestive tract, predominating in the
      larynx. Hypopharyngeal involvement is exceptional. Diagnosis is histological.
      Management depends on etiology. Local treatment is exceptional other than in case
      of complication. Systemic forms with associated myeloma are of poor prognosis.

PMID- 20822763
TI  - Obstructive congenital epulis.
AB  - INTRODUCTION: Congenital epulis, known as a congenital gingival granular cell
      tumor, is a benign tumor and very rare in newborns. Voluminous or multiple tumors
      can cause mechanical obstruction of the oral cavity and may result in postnatal
      feeding and respiratory problems. DISCUSSION: We report the clinical case of a
      female full-term newborn who presented a tumor on the upper gum obtruding into
      the oral cavity discovered at birth. The pregnancy was followed normally with
      three prenatal ultrasounds, which did not show abnormalities. The mass was
      excised under local anesthesia on the second day of life. The outcome was good
      after surgery and regular feedings were started on the second postoperative day.
      Histological examination confirmed the diagnosis of gingival tumor with granular
      cells and absence of signs of malignancy. CONCLUSION: Prenatal diagnosis is
      fundamental in the therapeutic approach to this rare lesion but remains difficult
      because the findings are non specific and the generally late development of the
      tumor.

PMID- 20822764
TI  - Transnasal endoscopic approach in the treatment of Graves ophthalmopathy: the
      value of a medial periorbital strip.
AB  - OBJECTIVES: Present our experience with orbital decompression using an endoscopic
      transnasal approach and test whether preservation of an anteroposterior
      periorbital strip overlying the medial rectus muscle can reduce the incidence of
      postoperative diplopia. PATIENT AND METHODS: Retrospective, descriptive study
      conducted on 16 patients with Graves ophthalmopathy operated on with orbital
      decompression between 2004 and 2009. RESULTS: Twelve women and four men (mean
      age, 34.6 years), a total of 30 orbits, were operated. A medial periorbital strip
      along the medial rectus muscle was preserved in 13 patients. A single case (7.7%)
      presented postoperative diplopia. The mean reduction of proptosis was 4.3mm.
      CONCLUSIONS: The endoscopic transnasal approach provides comparable results to
      those obtained with other techniques. The incidence of postoperative diplopia
      seems to decrease when an anteroposterior periorbital periosteal strip is
      preserved along the medial rectus muscle.

PMID- 20822765
TI  - Amyloid goiter: first manifestation of systemic amyloidosis.
AB  - Amyloidosis is an abnormal extracellular deposit, which can occur in several
      tissues. The mechanism is not clearly defined. In systemic amyloidosis, all the
      organs can be infiltrated, but amyloid goiter as the initial manifestation of
      systemic amyloidosis is an exceedingly rare condition. We report a rare case of a
      patient who presented an amyloid goiter as the first manifestation of systemic
      amyloidosis. This patient had a known Crohn's disease. He developed a goiter
      without compressive complications. Histologic examination revealed a diffuse
      amyloid deposition surrounding thyroid follicles. The gland was enlarged with an
      eosinophilic and amorphic deposit. Confirmation of amyloid was made by the
      presence of congophilia and apple-green birefringence under polarized-light
      microscopy. An immunoreactivity was seen with AA protein. Amyloid goiter is a
      rare manifestation of amyloidosis. About 250 cases of amyloid goiter have been
      reported in the literature. The goiter enlarges rapidly and progressively, often
      becoming compressive like thyroid cancer. The prognosis depends on the treatment
      of the amyloidosis and the underlying chronic disease.

PMID- 20822766
TI  - Supraglottic laryngeal paraganglioma.
AB  - INTRODUCTION: Laryngeal paraganglioma is a rare, mainly supraglottic, tumor.
      CLINICAL CASE: A 67-year-old woman was operated on in June 2009 for supraglottic
      laryngeal paraganglioma, with simple postoperative course. DISCUSSION:
      Anatomopathologic features, malignant paraganglioma and the various possible
      treatments are presented and discussed. Surgical exeresis with an external
      approach should in our opinion remain the reference treatment, for optimal
      control of exeresis of this potentially hemorrhagic tumor with risk of recurrence
      in case of incomplete exeresis.

PMID- 20822767
TI  - Maternal high-fat intake predisposes nonalcoholic fatty liver disease in C57BL/6
      offspring.
AB  - OBJECTIVE: This work aimed to verify the hypothesis that maternal intake of high
      fat diet in critical periods of pregnancy and/or suckling period predisposes
      nonalcoholic fatty liver disease in adult C57BL/6 mice offspring. STUDY DESIGN:
      Male pups were divided into 5 groups: (1) SC, from standard chow-fed dams; (2) G,
      from high-fat chow (HF)-fed dams during the gestation (G) period; (3) L, from HF
      fed dams during the lactation (L) period; (4) GL, from HF-fed dams during the
      gestation and lactation (GL) periods; and (5) GL/HF, from HF-fed dams during GL,
      maintaining an HF diet from postweaning to adulthood. We analyzed body mass,
      plasma blood, and liver structure. RESULTS: The G offspring showed insulin
      resistance and lower glucose transporter-2 expression. Hepatic steatosis was
      present in the G, L, GL, and mainly in GL/HF offspring. Sterol regulatory element
      binding protein-1c expression was higher in G, GL, and GL/HF offspring.
      CONCLUSION: Programming by HF chow predisposes hepatic adverse remodeling in the
      liver of adult offspring.

PMID- 20822768
TI  - Right-shift for non-speech motor processing in adults who stutter.
AB  - INTRODUCTION: In adults who do not stutter (AWNS), the control of hand movement
      timing is assumed to be lateralized to the left dorsolateral premotor cortex
      (PMd). In adults who stutter (AWS), the network of speech motor control is
      abnormally shifted to the right hemisphere. Motor impairments in AWS are not
      restricted to speech, but extend to non-speech orofacial and finger movements. We
      here investigated the lateralization of finger movement timing control in AWS.
      METHODS: We explored PMd function in 14 right-handed AWS and 15 age matched AWNS.
      In separate sessions, they received subthreshold repetitive transcranial magnetic
      stimulation (rTMS) for 20 min at 1Hz over the left or right PMd, respectively.
      Pre- and post-stimulation participants were instructed to synchronize their index
      finger taps of either hand with an isochronous sequence of clicks presented
      binaurally via earphones. Synchronization accuracy was measured to quantify the
      effect of the PMd stimulation. RESULTS: In AWNS inhibition of left PMd affected
      synchronization accuracy of the left hand. Conversely, in AWS TMS over the right
      PMd increased the asynchrony of the left hand. CONCLUSIONS: The present data
      indicate an altered functional connectivity in AWS in which the right PMd seems
      to be important for the control of timed non-speech movements. Moreover, the
      laterality-shift suggests a compensatory role of the right PMd to successfully
      perform paced finger tapping.

PMID- 20822769
TI  - Rates of screening colonoscopy are not increased when women are offered a female
      endoscopist in a health promotion outreach program.
AB  - BACKGROUND: In surveys, almost 50% of women prefer a female endoscopist (FE) to
      perform their screening colonoscopies (SCOs). OBJECTIVE: To assess whether
      offering women an FE is associated with higher rates of SCOs. DESIGN: Prospective
      cohort study. SETTING: University of Colorado Hospital primary care clinics.
      PATIENTS: Women of ages 50 to 69 years eligible for an SCO. INTERVENTIONS: SCO
      offers through mail and telephone outreach, with and without an explicit FE
      option. MAIN OUTCOME MEASUREMENTS: Outreach intervention differences in SCO
      completion rates and percentages of women requesting FE. RESULTS: Of 396 women,
      72 (18.2%) underwent SCO without difference by type of invitation. Women who
      received an FE invitation were more likely to request an FE than patients who
      received no invitation (44.2% and 4.8%, respectively, P < .001), but women who
      requested an FE were not more likely to undergo an SCO than those who did not.
      LIMITATIONS: SCO was offered through an outreach program rather than through in
      clinic referrals. The study used a nonrandomized trial comparison group.
      CONCLUSIONS: Women offered an FE were not more likely to undergo an SCO than
      those who were not. This study is unique in describing outcomes associated with
      actual offers of an FE at the time of scheduling. More direct evidence is needed
      to support the notion that the absence of FEs is an important barrier to
      colorectal cancer screening among women.

PMID- 20822770
TI  - Comparison of the TVT SECUR System "hammock" and "U" tape positions for
      management of stress urinary incontinence.
AB  - OBJECTIVE: To assess the efficacy and complications associated with use of the
      TVT SECUR System device with placement of the tape in either a "hammock" or "U"
      position for management of stress urinary incontinence (SUI). METHODS: A
      prospective study of patients with SUI allocated into one of two groups:
      "hammock" or "U" tape placement. Preoperative urodynamic results were compared
      with results at the 6-month and 1-year follow up. Outcome measures were objective
      cough test assessment and subjective patient responses to a questionnaire at
      follow up. RESULTS: Of 82 patients included in the study, 43 comprised the
      "hammock" group and 39 comprised the "U" group. The objective cure rate at 1-year
      follow up was 62.8% (n=27) in the "hammock" group and 71.8% (n=28) in the "U"
      group. At 1-year follow up, the subjective cure, improvement, and failure rates
      for the "hammock" group were 60.5%, 13.9%, and 25.7% respectively, and 69.2%,
      12.8%, and 17.9% respectively, for the "U" group. CONCLUSION: The efficacy of the
      TVT SECUR System was lower (<72%) than the cure rates reported for other TVT
      procedures; further studies are required.

PMID- 20822771
TI  - Determination of aldehydes in rainwater using micro-solid-phase extraction and
      high-performance liquid chromatography.
AB  - A simple and rapid extraction procedure was developed for determining aldehydes
      in rainwater samples. This extraction technique involved the use of micro-solid
      phase extraction in which the sorbent was held within a polypropylene membrane
      envelope, followed by high-performance liquid chromatographic analysis. Aldehydes
      such as formaldehyde, acetaldehyde, propionaldehyde and valeraldehyde were used
      as model compounds. Extraction conditions were optimized. The method linearity
      ranged between 0.5 and 50 MUgl(-1) with the correlation coefficient of 0.987
      0.999. The relative standard deviations (RSDs) of the method ranged from 7 to
      12%. Method detection limits were in the range of 0.07-0.15 MUgl(-1), which is
      lower than those previously reported for solid-phase microextraction combined
      with gas chromatography-mass spectrometric techniques. The proposed extraction
      technique was used for determination of aldehydes in rainwater samples to
      demonstrate the applicability of the method.

PMID- 20822772
TI  - Alternative sample-introduction technique to avoid breakthrough in gradient
      elution liquid chromatography of polymers.
AB  - Gradient-elution liquid chromatography (GELC) is a powerful tool for the
      characterization of synthetic polymers. However, gradient-elution chromatograms
      often suffer from breakthrough phenomena. Breakthrough can be averted by using a
      sample solvent as weak as the mobile phase. However, this approach is only
      applicable to polymers for which a sufficiently strong solvent exists which is at
      the same time a weak eluent. Finding such a solvent for a given polymer can be
      laborious or may even be impossible. Besides, when working with comprehensive two
      dimensional LC the effluent of the first dimension is the injection solvent of
      the second dimension. In this case, it is not possible to avoid breakthrough by
      adjusting the eluent strength of the second-dimension injection solvent.
      Therefore, another strategy to avert breakthrough has to be implemented. In this
      work, we successfully avoided breakthrough in GELC by mixing the mobile phase not
      before, but after the autosampler. This was demonstrated measuring a blend of
      poly(methyl methacrylate) standards with different molecular-weights as model
      mixture with comprehensive two-dimensional GELC*size-exclusion chromatography.
      The strategy is thought to be applicable to all substances with a sufficiently
      strong dependence of retention on mobile-phase composition. This typically
      applies to large molecules (synthetic and natural polymers) and allows efficient
      refocusing. Unretained and barely retained substances are not refocused and
      therefore suffer in the proposed setup from peak broadening.

PMID- 20822773
TI  - Water repellent porous silica films by sol-gel dip coating method.
AB  - The wetting of solid surfaces by water droplets is ubiquitous in our daily lives
      as well as in industrial processes. In the present research work, water repellent
      porous silica films are prepared on glass substrate at room temperature by sol
      gel process. The coating sol was prepared by keeping the molar ratio of
      methyltriethoxysilane (MTES), methanol (MeOH), water (H(2)O) constant at
      1:12.90:4.74, respectively, with 2M NH(4)OH throughout the experiments and the
      molar ratio (M) of MTES/Ph-TMS was varied from 0 to 0.22. A simple dip coating
      technique is adopted to coat silica films on the glass substrates. The static
      water contact angle as high as 164 degrees  and water sliding angle as low as 4
      degrees  was obtained for silica film prepared from M=0.22. The surface
      morphological studies of the prepared silica film showed the porous structure
      with pore sizes typically ranging from 200nm to 1.3MUm. The superhydrophobic
      silica films prepared from M=0.22 retained their superhydrophobicity up to a
      temperature of 285 degrees C and above this temperature the films became
      superhydrophilic. The porous and water repellent silica films are prepared by
      proper alteration of the Ph-TMS in the coating solution. The prepared silica
      films were characterized by surface profilometer, scanning electron microscopy
      (SEM), transmission electron microscopy (TEM), Fourier Transform Infrared (FT-IR)
      spectroscopy, humidity tests, chemical aging tests, static and dynamic water
      contact angle measurements.

PMID- 20822774
TI  - Characteristics of deformation and electrical charging of large water drops
      immersed in an insulating liquid on the electrode surface.
AB  - Electrical manipulation of charged droplet has attracted much attention owing to
      its potential applications in various industrial and laboratorial units. In this
      paper, deformation and electrical charging of large conductive water drops on the
      electrode surface studied experimentally. Moreover, the quality of drop motion
      and deformation near the electrode surface discussed in details by performing a
      precise image processing of the experimental photos. Based on the experimentally
      extracted drop shapes, the distribution of the electrical charge on the drop
      surface obtained numerically. The results revealed some important effects of the
      drop deformation on the amount of the acquired charge on the drop surface, which
      could be helpful to step forward in design of the electrically driven droplet
      based systems.

PMID- 20822775
TI  - In situ SAXS observation on metal-salt-derived alumina sol-gel system accompanied
      by phase separation.
AB  - The structure formation process of hierarchically porous alumina gels has been
      investigated by in situ small angle X-ray scattering (SAXS). The measurement was
      performed on the sol-gel solution containing aluminum chloride hexahydrate
      (AlCl(3).6H(2)O), poly(ethylene oxide) (PEO), and propylene oxide (PO). The
      temporal divergence of scattering intensity in the low q regime was observed in
      the early stage of reaction, indicating that the occurrence of spinodal
      decomposition-type phase separation. Detailed analysis of the SAXS profiles
      revealed that phase separation occurs between weakly branched polymerizing
      aluminum hydroxide (AH) and PEO. Further progress of the condensation reaction
      forms phase-separated two phases, that is, AH-rich phase and PEO-rich phase with
      the micrometer-range heterogeneity. The growth and aggregation of primary
      particles occurs in the phase-separated AH-rich domain, and therefore, the
      addition of PEO influences on the structure in nanometer regime as well as
      micrometer regime. The moderate stability of oligomeric species allows
      homogeneous condensation reaction parallel to phase separation and successful
      formation of hierarchically porous alumina gel.

PMID- 20822776
TI  - Production variability and single word intelligibility in aphasia and apraxia of
      speech.
AB  - This study was designed to estimate test-retest reliability of orthographic
      speech intelligibility testing in speakers with aphasia and AOS and to examine
      its relationship to the consistency of speaker and listener responses.
      Monosyllabic single word speech samples were recorded from 13 speakers with
      coexisting aphasia and AOS. These words were transcribed phonetically by two
      trained listeners and also presented to non-brain-damaged listeners for
      identification in a computerized speech intelligibility test. Overall
      intelligibility scores were computed for each speaker, and word-by-word responses
      for individual words were examined for both speaker and listener consistency. The
      clinical feasibility of the approach was supported by a strong correlation
      between scores from the phonetic transcription and speech intelligibility tests
      and by strong test-retest reliability for all speakers. Detailed analyses of
      individual responses indicated that the intelligibility test stability was not
      due to consistency either in the kind of errors speakers made or in the responses
      listeners gave when they heard a word different from the target. LEARNING
      OUTCOMES: The reader will be able to describe the purpose of single word speech
      intelligibility testing in individuals with aphasia and apraxia of speech and to
      discuss the relationship between word-by-word production consistency and overall
      test-retest reliability.

PMID- 20822777
TI  - The development of norm-based coding and race-specific face prototypes: an
      examination of 5- and 8-year-olds' face space.
AB  - The current research investigated the organization of children's face space by
      examining whether 5- and 8-year-olds show race-contingent aftereffects.
      Participants read a storybook in which Caucasian and Chinese children's faces
      were distorted in opposite directions. Before and after adaptation, participants
      judged the normality/attractiveness of expanded, compressed, and undistorted
      Caucasian and Chinese faces. The method was validated with adults and then
      refined to test 8- and 5-year-olds. The 5-year-olds were also tested in a simple
      aftereffects paradigm. The current research provides the first evidence for
      simple attractiveness aftereffects in 5-year-olds and for race-contingent
      aftereffects in both 5- and 8-year-olds. Evidence that adults and 5-year-olds may
      possess only a weak prototype for Chinese children's faces suggests that
      Caucasian adults' prototype for Chinese adult faces does not generalize to child
      faces and that children's face space undergoes a period of increasing
      differentiation between 5 and 8 years of age.

PMID- 20822779
TI  - Human health benefits supplied by Mediterranean marine biodiversity.
AB  - This paper summarizes the overall benefits supplied by Mediterranean marine
      biodiversity to human health and highlights the anthropogenic and environmental
      causes that are threatening these benefits. First, the Mediterranean Sea is a
      valuable source of seafood, which is an important component of the so-called
      "Mediterranean diet". This type of diet has several health benefits, including
      cardio and cancer protective effects, which are attributed to the high intake of
      seafood-derived n-3 (omega-3) fatty acids. Second, the Mediterranean marine
      organisms, particularly the benthic ones, have furnished a large variety of
      bioactive metabolites, some of which are being developed into new drugs to threat
      major human diseases such as cancer. Third, the Mediterranean coastal areas
      provide environments for practising maritime leisure activities that provide
      physical and psychological benefits to users. Despite all this, fishing, tourism,
      contamination and sea warming are deteriorating this rich marine ecosystem, which
      needs to be protected to assure human welfare.

PMID- 20822778
TI  - Quality of life and functional impairment in compulsive hoarding.
AB  - Compulsive hoarding patients have been found in previous studies to have
      substantial disability and functional impairment. However, no prior study has
      examined subjective and objective quality of life (QOL) in patients with
      compulsive hoarding. This present study compared compulsive hoarders and non
      hoarding OCD patients across a variety of QOL domains. Subjects were 171
      consecutive adult patients (34 compulsive hoarders, 137 non-hoarding patients
      with DSM-IV OCD) treated openly between 1998 and 2004 in the UCLA OCD Partial
      Hospitalization Program (OCD PHP), a specialized, intensive, multi-modal
      treatment program for treatment-refractory patients. Scores on the Quality of
      Life Scale and other symptom severity measures on admission were compared between
      compulsive hoarders and non-hoarding OCD patients. Compulsive hoarders were older
      and had lower global functioning than non-hoarding OCD patients. Both groups had
      low overall QOL scores across multiple domains. Compulsive hoarders had
      significantly lower levels of satisfaction with their safety than non-hoarding
      OCD patients, were more often the victims of both violent and non-violent crime,
      felt less safe in their neighborhoods, and felt less protected against attack.
      Compulsive hoarders were also much less satisfied with their living arrangements
      than non-hoarding OCD patients. No differences were found on financial variables,
      but the vast majority of patients in both groups were unemployed. Compulsive
      hoarders have lower QOL than non-hoarding OCD patients in the domains of safety
      and living situation. Psychosocial rehabilitation that focuses on problems with
      victimization, safety, employment, and financial areas may be a beneficial
      augmentation to treatment for compulsive hoarding.

PMID- 20822780
TI  - Influence of tracer selection on protein synthesis rates at rest and postexercise
      in multiple human muscles.
AB  - The goal of this investigation was to assess the influence of tracer selection on
      mixed muscle fractional synthesis rate (FSR) at rest and postexercise during
      amino acid infusion in multiple human skeletal muscles. Fractional synthesis rate
      was measured before and 24 hours after 45 minutes of running using simultaneous
      infusion of [(2)H(5)]-phenylalanine (Phe) and [(2)H(3)]-leucine (Leu) coupled
      with muscle biopsies from the vastus lateralis and soleus in aerobically trained
      men (n = 8; age, 26 +/- 2 years). Mixed muscle protein FSR was analyzed by gas
      chromatography-mass spectrometry combined with a standard curve using the
      enriched muscle tissue fluid as the precursor pool. To control for potential
      analytical differences between tracers, all samples and standards for both
      tracers were matched for m + 0 abundance. Tracer selection did not influence
      resting FSR for the vastus lateralis or soleus (P > .05). Fractional synthesis
      rate measured 24 hours postexercise was higher (P < .05) compared with rate at
      rest and was similar between tracers for the vastus lateralis (Phe, 0.110% +/-
      0.010%.h(-1); Leu, 0.109% +/- 0.005%.h(-1)) and soleus (Phe, 0.123% +/- 0.008%.h(
      1); Leu, 0.122% +/- 0.005%.h(-1)). These data demonstrate that tracer selection
      does not influence the assessment of resting or postexercise FSR, thereby
      supporting the use of both [(2)H(5)]-phenylalanine and [(2)H(3)]-leucine for the
      measurement of FSR in exercise-based studies of human skeletal muscle.

PMID- 20822781
TI  - Phenolic dimers and an indole alkaloid from Campylospermum flavum (Ochnaceae).
AB  - From the leaves and stem bark of Campylospermum flavum (Ochnaceae), three
      compounds, namely 4'''-O-methylagathisflavone, flavumchalcone, and flavumindole
      have been isolated together with 10 known compounds, including three flavonoids,
      two biflavonoids, two alkaloids, two nitrile glucosides, and glucopyranosyl-beta
      sistosterol. The structures of these compounds and their relative configurations
      were established by 1D and 2D NMR experiments. The methanolic crude extracts of
      leaves and stem bark of C. flavum and compounds displayed a significant
      cytotoxicity towards Artemia salina larvae.

PMID- 20822782
TI  - Phenolic glucosides from Hasseltia floribunda.
AB  - The leaves of Hasseltia floribunda were examined for their chemical constituents.
      Twelve phenolic glucosides, namely three hydroxycyclohexenyl acyl glucosides,
      four acylated salicortin derivatives, and five coumaroyl salicin derivatives,
      were isolated along with eight known phenolic glycosides, six known flavones, and
      two known sesquiterpenoid cyclohexenone derivatives. The structures of the
      isolated compounds were elucidated by NMR spectroscopic and HRMS spectrometric
      methods and by comparing analytical data with those of related structures.

PMID- 20822783
TI  - TNF-alpha inhibitory diterpenoids from the Chinese mangrove plant Excoecaria
      agallocha L.
AB  - Chemical examination of the stems and twigs of the mangrove plant Excoecaria
      agallocha L. resulted in the isolation of six ent-kaurane diterpenoids named
      agallochaols K-P (1-6), an atisane-type diterpenoid agallochaol Q (7), along with
      eight known diterpenoids (8-15). Their structures were elucidated on the basis of
      extensive spectroscopic analysis and by comparison of their NMR spectroscopic
      data with those reported in literature, in association with the biogenetic
      relationship with the X-ray structure of 9. Compounds 1, 5-7, 9-10, and 13 showed
      anti-inflammatory potency to suppress expression of NF-kappaB and AP-1 targeted
      genes including TNF-alpha and IL-6 induced by lipopolysaccharide (LPS) in mouse
      macrophages Raw 264.7 cells. In addition, compounds 1, 5-7, 9-10, and 13 block NF
      kappaB activation, while compounds 1 and 7 block AP-1 activation dramatically,
      indicating these compounds possess an anti-inflammatory potential in vitro.

PMID- 20822784
TI  - Xanthine oxidase inhibitory terpenoids of Amentotaxus formosana protect cisplatin
      induced cell death by reducing reactive oxygen species (ROS) in normal human
      urothelial and bladder cancer cells.
AB  - The diterpenoids (+)-ferruginol (1), ent-kaur-16-en-15-one (2), ent-8(14),15
      sandaracopimaradiene-2alpha,18-diol (3), 8(14),15-sandaracopimaradiene
      2alpha,18,19-triol (4), and (+)-sugiol (5) and the triterpenoids 3beta
      methoxycycloartan-24(24(1))-ene (6), 3beta,23beta-dimethoxycycloartan-24(24(1))
      ene (7), 3beta,23beta-dimethoxy-5alpha-lanosta-24(24(1))-ene (8), and 23(S)-23
      methoxy-24-methylenelanosta-8-en-3-one (9), isolated from Amentotaxus formosana,
      showed inhibitory effects on xanthine oxidase (XO). Of the compounds tested,
      compound 5 was a potent inhibitor of XO activity, with an IC(50) value of 6.8+/
      0.4 MUM, while displaying weak ABTS radical cation scavenging activity. Treatment
      of the bladder cancer cell line, NTUB1, with 3-10 MUM of compound 5 and 10 MUM
      cisplatin, and immortalized normal human urothelial cell line, SV-HUC1, with 0.3
      1 MUM and 10-50 MUM of compound 5 and 10 MUM cisplatin, respectively, resulted in
      increased viability of cells compared with cytotoxicity induced by cisplatin.
      Treatment of NTUB1 with 20 MUM cisplatin and 10 or 30 MUM of compound 5 resulted
      in decreased ROS production compared with ROS production induced by cisplatin.
      These results indicate that 10 or 30 MUM of compound 5 in NTUB1 cells may mediate
      through the suppression of XO activity and reduction of reactive oxygen species
      (ROS) induced by compound 5 cotreated with 20 MUM cisplatin and protection of
      subsequent cell death.

PMID- 20822785
TI  - [Psychotic disorder revealing epilepsy linked to a dysembryoma of the left
      hippocampus].
AB  - INTRODUCTION: Psychotic symptoms are a rare but well-known complication of
      epilepsy. The prevalence is estimated between 4 and 9%. PATIENT: We report a case
      of a 40-year-old patient, unrecognized epileptic, who presented an acute
      psychotic syndrome which seemed to be of functional origin, the EEG performed
      during the episode, and the cerebral CT scan being normal. Nevertheless, the
      clinical presentation, especially the sudden ending of delusions, led to further
      investigations. Careful history taking and repeated EEG recordings allowed the
      diagnosis of partial epilepsy that had begun 17 years earlier and symptomatic of
      a dysembryoplastic tumour of the left hippocampus revealed by MRI. DISCUSSION AND
      CONCLUSION: Search for an epileptic origin of an acute psychotic syndrome must
      always be undertaken by systematic EEG. The possibility of a symptomatic temporal
      tumor must not be overlooked.

PMID- 20822786
TI  - Calculation of the effect of pressurizing gases on the resonant modes of single
      crystal parallelepiped.
AB  - Resonant ultrasound spectroscopy provides for an experimental determination of
      the elastic moduli of a solid sample. The moduli are extracted by matching a
      theoretically computed resonant spectrum to the experimental vibrational
      spectrum. To determine the pressure dependence of the moduli, the vibrational
      spectrum can be taken with the sample in a pressurizing gas. Then the extraction
      of the intrinsic, pressure dependent moduli requires a theoretical treatment
      which permits removal of the perturbation of the spectrum due to the surface
      loading by the pressure and shear waves in the gas. In order to illustrate a
      treatment which accomplishes this removal, the theoretically computed frequency
      shifts and the quality factors are reported for two single-crystal parallelepiped
      pressurized by noble gases.

PMID- 20822787
TI  - Lipoprotein lipase and hepatic triglyceride lipase reduce the infectivity of
      hepatitis C virus (HCV) through their catalytic activities on HCV-associated
      lipoproteins.
AB  - The effect of lipolysis by lipoprotein lipase (LPL) and hepatic triglyceride
      lipase (HTGL) on hepatitis C virus (HCV) infection was evaluated. First, medium
      from HuH7.5 cells bearing HCV genome replication was treated with LPL. LPL
      treatment led to reduced HCV infectivity, shifted HCV to higher densities, and
      lowered the amount of apolipoprotein E-associated HCV. The effect of endogenous
      HTGL secreted from HuH7.5 on HCV infectivity was next examined. Neutralization of
      HTGL by an anti-HTGL antibody resulted in suppression of LPL-induced reduction in
      infectivity of HCV-bearing medium, while knockdown of HTGL by siRNA led to
      increased HCV infectivity irrespective of LPL. HCV in medium from HTGL knockdown
      cells was found in fractions with a lower density. These results indicate that
      changes in the nature of HCV-associated lipoproteins by LPL and/or HTGL affect
      HCV infectivity, suggesting that association of HCV with specific lipoproteins is
      important for HCV infectivity.

PMID- 20822788
TI  - Establishment of a cynomolgus macaque model of influenza B virus infection.
AB  - Pathogenicity of influenza B virus was examined in cynomolgus macaques to
      establish a macaque model suitable for vaccine and antiviral drug development. We
      prepared influenza B viruses for inoculation with minimal passages after
      isolation from patients. Macaques inoculated with influenza B virus showed higher
      body temperature than that before infection for 6 to 12 days. Virus was detected
      in nasal, tracheal, and bronchial samples until 6 days after inoculation followed
      by an increase in neutralizing antibody. High levels of IL-6 and TNF-alpha in
      nasal swabs from the infected macaques were correlated with fever. Symptoms and
      duration of the viral replication would be sufficient to evaluate efficacy of
      vaccines and antiviral agents. In addition, measurement of immune responses
      including antibody and cytokine production would provide an immunological
      rationale in efficacy of vaccines and antiviral agents. The results suggest that
      cynomolgus macaques are appropriate model animals for research of influenza B
      virus.

PMID- 20822789
TI  - The second extracellular loop dictates Occludin-mediated HCV entry.
AB  - Recent findings have implicated tight junction (TJ) protein Occludin (OCLN) as an
      essential factor for hepatitis C virus (HCV) to enter human hepatocytes. To gain
      insights into OCLN-mediated HCV entry, we created a panel of OCLN deletion
      mutants and found that without impairing OCLN's cell surface localization,
      removal of the extracellular loop 2 (EL2) from OCLN abolished both its ability to
      mediate HIV-HCV pseudotypes' (HCVpp) entry as well as its ability to
      coprecipitate HCV glycoprotein E2. Recombinant OCLN EL2, however, failed to
      robustly bind soluble E2 (sE2) in pull-down assays. Subsequent studies revealed
      that OCLN formed complex with Dynamin II, an important GTPase for endocytosis, in
      an EL2-dependent fashion. HCVpp, as well as cell culture grown HCV (HCVcc), was
      sensitive to Dynamin knockdown or inhibition. We conclude that OCLN EL2 dictates
      the Dynamin-dependent HCV entry. Furthermore, OCLN could function to bridge
      virions to Dynamin-dependent endocytic machineries.

PMID- 20822790
TI  - Biological nitrogen removal with a real-time control strategy using moving slope
      changes of pH(mV)- and ORP-time profiles.
AB  - A new real-time control strategy using moving slope changes of oxidation
      reduction potential (ORP)- and pH(mV)-time profiles was designed. Its
      effectiveness was evaluated by operating a farm-scale sequencing batch reactor
      (SBR) process using the strategy. The working volume of the SBR was 18 m(3), and
      the volumetric loading rate of influent was 1 m(3) cycle(-1). The SBR process
      comprised six phases: feeding -> anoxic -> anaerobic -> aerobic -> settle ->
      discharge. The anoxic and aerobic phases were controlled by the developed real
      time control strategy. The nitrogen break point (NBP) in the pH(mV)-time profile
      and the nitrate knee point (NKP) in the ORP-time profile were designated as real
      time control points for the aerobic and anoxic phases, respectively. Through
      successful real-time control, the duration of the aerobic and anoxic phases could
      be optimized and this resulted in very high N removal and a flexible hydraulic
      retention time. Despite the large variation in the loading rate (0.5-1.8 kg NH(4)
      N m(-3) cycle(-1)) due to influent strength fluctuation, complete removal of
      NH(4)-N (100%) was always achieved. The removal efficiencies of soluble nitrogen
      (NH(4)-N plus NO(x)-N), soluble total organic carbon, and soluble chemical oxygen
      demand were 98%, 90%, and 82%, respectively. Monitoring the ORP and pH(mV)
      revealed that pH(mV) is a more reliable control parameter than ORP for the real
      time control of the oxic phase. In some cases, a false NBP momentarily appeared
      in the ORP-time profile but was not observed in the pH(mV)-time profile. In
      contrast, ORP was more the reliable control parameter for NKP detection in the
      anoxic phase, since the appearance of NKP in the pH(mV)-time profile was
      sometimes vague.

PMID- 20822791
TI  - Mn oxide coated catalytic membranes for a hybrid ozonation-membrane filtration:
      comparison of Ti, Fe and Mn oxide coated membranes for water quality.
AB  - In this study the performance of catalytic membranes in a hybrid ozonation
      ceramic membrane filtration system was investigated. The catalytic membranes were
      produced by coating commercial ceramic ultrafiltration membranes with manganese
      or iron oxide nanoparticles using a layer-by-layer self-assembly technique. A
      commercial membrane with a titanium oxide filtration layer was also evaluated.
      The performance of the coated and uncoated membranes was evaluated using water
      from a borderline eutrophic lake. The permeate flux and removal of the organic
      matter was found to depend on the type of the metal oxide present on the membrane
      surface. The performance of the manganese oxide coated membrane was superior to
      that of the other membranes tested, showing the fastest recovery in permeate flux
      when ozone was applied and the greatest reduction in the total organic carbon
      (TOC) in the permeate. The removal of trihalomethanes (THMs) and haloacetic acids
      (HAAs) precursors using the membrane coated 20 times with manganese oxide
      nanoparticles was significantly better than that for the membranes coated with 30
      or 40 times with manganese oxide nanoparticles or 40 times with iron oxide
      nanoparticles.

PMID- 20822792
TI  - Mechanisms of SMP production in membrane bioreactors: choosing an appropriate
      mathematical model structure.
AB  - Being able to predict the soluble microbial product (SMP) concentration, an
      important foulant in membrane bioreactors (MBRs), with mathematical models
      provides the opportunity to use foulant production as an MBR design and
      optimization parameter. This study examined the ability of three mathematical
      model structures to describe two distinct mechanisms of SMP production. The
      production mechanisms evaluated are (1) the erosion or hydrolysis of floc
      associated extracellular polymeric substance (EPS) and (2) decay of active cells.
      The models were compared based on their ability to predict SMP concentrations
      observed in an MBR system during a period of increased SMP and floc-associated
      EPS production due to increased predation. Predation was an important contributor
      to overall biomass decay. Short-term batch experiments were also preformed to
      examine model assumptions related to the (1) production of SMP due to decay of
      active cells, (2) production of SMP due to erosion of floc-associated EPS, (3)
      degradability of SMP present in the MBR mixed liquor during increased predation
      and (4) degradability of eroded floc-associated EPS. Both erosion of floc
      associated EPS and decay of active cells were shown to be important independent
      mechanisms of SMP production. Therefore, a mathematical model used to predict SMP
      concentrations should provide the ability to capture both mechanisms
      independently. SMP produced during increased predation were slowly degradable
      while eroded floc-associated EPS was rapidly degradable. Model results
      demonstrate that the slowly biodegradable SMP fraction will dominate the bulk
      phase SMP concentration.

PMID- 20822793
TI  - Autotrophic nitrogen removal from black water: calcium addition as a requirement
      for settleability.
AB  - Black (toilet) water contains half of the organic load in the domestic
      wastewater, as well as the major fraction of the nutrients nitrogen and
      phosphorus. When collected with vacuum toilets, the black water is 25 times more
      concentrated than the total domestic wastewater stream, i.e. including grey water
      produced by laundry, showers etc. A two-stage nitritation-anammox process was
      successfully employed and removed 85%-89% of total nitrogen in anaerobically
      treated black water. The (free) calcium concentration in black water was too low
      (42 mg/L) to obtain sufficient granulation of anammox biomass. The granulation
      and retention of the biomass was improved considerably by the addition of 39 mg/L
      of extra calcium. This resulted in a volumetric nitrogen removal rate of 0.5
      gN/L/d, irrespective of the two temperatures of 35  degrees C and 25  degrees C
      at which the anammox reactors were operated. Nitrous oxide, a very strong global
      warming gas, was produced in situations of an incomplete anammox conversion
      accompanied by elevated levels of nitrite.

PMID- 20822794
TI  - Estimating true human and animal host source contribution in quantitative
      microbial source tracking using the Monte Carlo method.
AB  - Cultivation- and library-independent, quantitative PCR-based methods have become
      the method of choice in microbial source tracking. However, these qPCR assays are
      not 100% specific and sensitive for the target sequence in their respective
      hosts' genome. The factors that can lead to false positive and false negative
      information in qPCR results are well defined. It is highly desirable to have a
      way of removing such false information to estimate the true concentration of host
      specific genetic markers and help guide the interpretation of environmental
      monitoring studies. Here we propose a statistical model based on the Law of Total
      Probability to predict the true concentration of these markers. The distributions
      of the probabilities of obtaining false information are estimated from
      representative fecal samples of known origin. Measurement error is derived from
      the sample precision error of replicated qPCR reactions. Then, the Monte Carlo
      method is applied to sample from these distributions of probabilities and
      measurement error. The set of equations given by the Law of Total Probability
      allows one to calculate the distribution of true concentrations, from which their
      expected value, confidence interval and other statistical characteristics can be
      easily evaluated. The output distributions of predicted true concentrations can
      then be used as input to watershed-wide total maximum daily load determinations,
      quantitative microbial risk assessment and other environmental models. This model
      was validated by both statistical simulations and real world samples. It was able
      to correct the intrinsic false information associated with qPCR assays and output
      the distribution of true concentrations of Bacteroidales for each animal host
      group. Model performance was strongly affected by the precision error. It could
      perform reliably and precisely when the standard deviation of the precision error
      was small (<= 0.1). Further improvement on the precision of sample processing and
      qPCR reaction would greatly improve the performance of the model. This
      methodology, built upon Bacteroidales assays, is readily transferable to any
      other microbial source indicator where a universal assay for fecal sources of
      that indicator exists.

PMID- 20822795
TI  - Enzymatic hydrolysis of structurally diverse phthalic acid esters by porcine and
      bovine pancreatic cholesterol esterases.
AB  - A weak hydrolyzing activity against bis (2-ethylhexyl) phthalate (DEHP) was
      discovered in a commercial crude lipase (EC 3.1.1.3) preparation from porcine
      pancreas. DEHP was hydrolyzed to mono (2-ethylhexyl) phthalate (MEHP) not by a
      pancreatic lipase but by a cholesterol esterase (CEase, EC 3.1.1.13), a trace
      contaminant in the crude lipase preparation. Enzymatic hydrolysis of phthalic
      acid esters (PAEs), suspected to be endocrine-disrupting chemicals, was
      investigated using CEases from two species of mammals and a microorganism. Eight
      structurally diverse PAEs, namely diethyl phthalate (DEP), di-n-propyl phthalate
      (DPrP), di-n-butyl phthalate (DBP), di-n-pentyl phthalate (DPeP), di-n-hexyl
      phthalate (DHP), DEHP, n-butyl benzyl phthalate (BBP), and dicyclohexyl phthalate
      (DCHP), were hydrolyzed to their corresponding monoesters by both porcine and
      bovine pancreatic CEases, while a microbial CEase from Pseudomonas sp. had no
      hydrolyzing activity against these PAEs. The hydrolysis experiments with bovine
      pancreatic CEase (50 U) indicated complete hydrolysis of every PAE (5 MUmole)
      except for BBP and DCHP within 15 min; BBP and DCHP were hydrolyzed within 30 min
      and 6h, respectively. The rates of PAE hydrolysis could be affected by the
      bulkiness of alkyl side chains in the PAEs. This study provides important
      evidence that mammalian pancreatic CEases, such as those from porcine and bovine
      sources, are potential enzymes for nonspecific degradation of structurally
      diverse PAEs.

PMID- 20822796
TI  - Effect of hybrid UV-thermal energy stimuli on inactivation of S. epidermidis and
      B. subtilis bacterial bioaerosols.
AB  - Bioaerosols have become an increasingly important issue due to their harmful
      effects on human health. As the concern over airborne microorganisms grows, so
      does the need to develop and study efficient methods of controlling them. In this
      study, we designed a hybrid system involving ultraviolet (UV) irradiation and
      thermal energy and investigated its effects on bacterial bioaerosols, followed by
      a comparison with thermal energy alone and UV irradiation alone. The results show
      that the hybrid effect caused no variation in the shape of the normalized
      particle size distributions of S. epidermidis and B. subtilis bioaerosols.
      However, a physical transport loss of bacterial bioaerosols developed as the
      temperature inside the glass quartz tube increased. When bacterial bioaerosols
      were simultaneously exposed to UV irradiation and thermal energy for less than
      1.05 s, more than 99% of S. epidermidis bioaerosols were inactivated at 120 
      degrees C with exposure to one UV lamp and at 80  degrees C with exposure to two
      UV lamps; and 93.5% and 98.5% of B. subtilis bioaerosols were inactivated at 280 
      degrees C with exposure to one and two UV lamps, respectively. Moreover, the
      hybrid UV-thermal stimuli significantly reduced the concentration of ozone, which
      is a secondary UV-induced pollutant. Our results show that to obtain the same
      inactivation efficiency, the hybrid UV-thermal stimuli were more efficient than
      thermal energy alone in terms of energy consumption and produced significantly
      less ozone than UV irradiation alone. The hybrid stimuli also had higher
      inactivation efficiency than UV alone. Therefore, these results provide valuable
      information for the development of new methods for controlling bioaerosols.

PMID- 20822797
TI  - Use of native species Crenicichla menezesi (Ariidae) as a model for in situ
      evaluation of genotoxicity in surface water.
AB  - The aim of this work was to analyze the genotoxicity in surface water from the
      Pitimbu River (Natal, Brazil) using a neotropical species Crenicichla menezesi as
      bioindicator for in situ evaluation. The genotoxicity was analyzed using the
      micronucleus (MN) and comet assays in erythrocytes. The animals were collected
      from five sites of the river. A significant increase of MN frequency and comet
      class L1 to L4 were observed only in specimens collected from three sampling
      sites (SS3, SS4 and SS5) located into urban areas. These same sites also
      presented high metals concentration. Correlation of DNA damage and concentrations
      of Cu (Spearman r=0.8080), Cr (Spearman r=0.9772), and Ni (Spearman r=0.9909)
      were observed. These data indicate the presence of genotoxic agents. Moreover the
      C. menezesi species showed to be a good indicator for prompt analyses since this
      species presents sedentary and carnivore habits.

PMID- 20822798
TI  - Injection of botulinum toxin for treatment of chronic lateral epicondylitis:
      systematic review and meta-analysis.
AB  - OBJECTIVES: Lateral epicondylitis can be chronic and difficult to manage with
      conservative measures such as physical therapy and corticosteroid injection. We
      attempted to determine the efficacy of botulinum toxin for the treatment of
      chronic lateral epicondylitis. METHODS: We searched PubMed, MEDLINE, CINAHL,
      Google Scholar, EMBASE, PEDro, and ISI web of Science databases from inception
      until November 2009. Studies were included if they used any formulation of
      botulinum toxin A for treatment of chronic lateral epicondylitis and reported at
      least 1 pain outcome. One author extracted the relevant data using a standardized
      data extraction sheet and a second author checked the data. We performed a meta
      analysis by computing effect sizes for each study separately for pain and grip
      strength at 3 months after injection. Impact of bias was assessed independently
      by 2 authors. RESULTS: The search found 10 studies relevant to the question. Four
      of these were randomized controlled trials that could be pooled in a meta
      analysis. Results showed a moderate effect for pain favoring botulinum toxin
      (effect size -0.5, 95% CI -0.9, -0.1, I(2) = 56%) at 3 months and a no effect for
      grip strength. Qualitative analysis of the studies that could not be pooled also
      showed improvement in pain, but was limited by potential bias. CONCLUSIONS:
      Present literature provides support for use of botulinum toxin A injections into
      the forearm extensor muscles (60 units) for treatment of chronic treatment
      resistant lateral epicondylitis. It is minimally invasive and can be performed in
      an outpatient setting.

PMID- 20822799
TI  - British isles survey of methotrexate monitoring practice during treatment of
      juvenile idiopathic arthritis.
AB  - OBJECTIVES: We surveyed current pediatric rheumatology monitoring practice in
      methotrexate treatment of juvenile idiopathic arthritis in the British Isles, and
      experiences of significant side effects during methotrexate monitoring. METHODS:
      Single-center responses were sought from the current British Society for
      Pediatric and Adolescent Rheumatology membership, using a web-based survey tool.
      RESULTS: Thirty-three centers across the British Isles responded. Twenty-eight
      centers reported following British Society for Pediatric and Adolescent
      Rheumatology or local guidelines. Thirty-one centers were willing to modify their
      monitoring practice to individual circumstances. All centers used a full blood
      count and liver enzymes as monitoring tests. There was variation in frequency at
      which monitoring tests were performed, both at initiation of methotrexate therapy
      and once methotrexate therapy was established; 27 centers were willing to change
      the frequency of monitoring blood tests after a period of stability. Centers
      reported acting on alanine aminotransferase values ranging from 50 to 500 IU/L.
      Particular variation existed between smaller and larger centers. Few centers
      reported any experience of serious side effects, and only 1 cited a case of liver
      cirrhosis. CONCLUSIONS: Despite specific pediatric guidance for monitoring low
      dose methotrexate use in juvenile idiopathic arthritis, variation in practice
      exists in the British Isles. It may be that blood test monitoring could safely be
      performed less frequently than currently recommended. To inform future changes to
      guidance, we suggest establishing a prospective registry for serious side
      effects.

PMID- 20822800
TI  - Detection of cardiovascular system involvement in Behcet's disease using
      fluorodeoxyglucose positron emission tomography.
AB  - OBJECTIVES: Behcet's disease (BD) theoretically affects all sizes and types of
      vessels; however, there have been few reports describing the clinical efficacy of
      using (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients
      with BD. METHODS: Eight patients who were registered at the BD Specialty Clinic
      of Severance Hospital between 2004 and 2008 underwent FDG-PET scans to evaluate
      the cardiovascular presentations associated with BD. Medical records and FDG-PET
      images of the patients were retrospectively reviewed to determine the clinical
      significance of the cardiovascular findings. RESULTS: The median quantitative FDG
      uptake index was 1.46 (range, 0.58-2.61). FDG uptake was detected in multiple
      pseudoaneurysms, aortitis and arteritis associated with aortic regurgitation, and
      aneurysmatic dilation of the sinus of Valsalva, atherosclerotic change of the
      proximal ascending aorta associated with aortic regurgitation, and multiple
      pulmonary artery aneurysms. The quantitative FDG uptake intensity was
      significantly associated with the ESR level. CONCLUSIONS: FDG-PET scans may have
      clinical value as a workup study for patients with BD who have cardiovascular
      presentations.

PMID- 20822801
TI  - Trans-rectal ultrasound-coupled spectral optical tomography of total hemoglobin
      concentration enhances assessment of the laterality and progression of a
      transmissible venereal tumor in canine prostate.
AB  - OBJECTIVES: To evaluate whether trans-rectal spectral optical tomography of total
      hemoglobin concentration (HbT) can image longitudinal and lateral developments of
      a canine transmissible venereal tumor (TVT) in a canine prostate. METHODS: A near
      infrared (NIR) applicator was integrated with a trans-rectal ultrasound (TRUS)
      transducer to perform ultrasound (US)-coupled optical tomography of the canine
      prostate. Spectral detection at 785 and 830 nm enabled quantitation of HbT.
      Canine TVT cells were injected into the right lobe of a dog's prostate gland.
      Longitudinal imaging assessment of the post-injection prostate was performed by
      coupled US/NIR imaging over a 45-day duration. RESULTS: By day 7, NIR indicated
      TVT infiltration in the noninjected left prostatic lobe with the gray-scale US
      indistinct. By day 31, both NIR and gray-scale US revealed more widespread TVT
      involvement in the left than in the right lobe, as well as an extensive TVT mass
      in the caudal aspect of the gland, of which the peak HbT increased 3-fold and the
      mass volume grew exponentially over the 45-day duration. Increased blood supply
      to the mass was also observed on Doppler US. CONCLUSIONS: TRUS-coupled spectral
      optical tomography enhances assessment of the laterality and progression of
      prostate tumor compared with using gray-scale and Doppler TRUS.

PMID- 20822802
TI  - Immunization with synthetic VEGF peptides in ovarian cancer.
AB  - OBJECTIVE: To assess the role of active immunotherapy targeting VEGF with a
      peptide vaccine as a potential treatment for ovarian cancer. METHODS: A peptide
      vaccine targeting antigenic B-cell epitopes of VEGF were identified and linked to
      a promiscuous T-cell epitope. Elicited antibodies were assessed for their ability
      to recognize the VEGF protein, inhibit angiogenesis, inhibit the interaction of
      VEGF with its receptor, and inhibit cancer growth in mice. RESULTS: Following
      immunization, high-titered elicited antibodies were shown to be specific for the
      full-length VEGF protein by ELISA and Western blot. Anti-VEGF peptide antibodies
      inhibited cellular migration, proliferation, invasion, tube formation, and growth
      of aortic ring cultures. These antibodies inhibited the interaction between VEGF
      and its receptor (VEGFR2) in a concentration-dependent manner. Confirmation of
      this mechanism was demonstrated through inhibition of VEGFR2 phosphorylation
      following culture of human endothelial vein endothelial cells with anti-VEGF
      peptide antibodies. These antibodies were shown to inhibit ovarian cancer
      xenograft growth in a nude mouse model following intraperitoneal passive
      immunization. Active immunization with the VEGF peptide vaccine inhibited VEGF
      dependent pancreatic islet cell tumor growth in RIP1-Tag2 transgenic mice and was
      associated with decreased vasculogenesis in these tumors compared with animals
      vaccinated with an irrelevant peptide. Active immunization also inhibited growth
      of tumors from a VEGF overexpressing ovarian cancer cell line, resulting in
      decreased tumor size and tumor vessel density compared with control mice.
      CONCLUSIONS: Active immunization with VEGF peptides elicits antibodies that
      inhibit tumor growth by blocking VEGF-dependent angiogenesis.

PMID- 20822803
TI  - Hybrid imaging by SPECT/CT for sentinel lymph node detection in patients with
      cancer of the uterine cervix.
AB  - INTRODUCTION: Conventional lymphoscintigraphy provides planar images with little
      spatial information on location of pelvic sentinel lymph nodes (SLN). SPECT has
      better spatial resolution and, in combination with anatomic accuracy provided by
      CT improves SLN preoperative localization. The aim of the study was to report on
      the results of hybrid imaging of SLN in early cervical cancer patients treated at
      Claudius Regaud Cancer Center. METHODS: Stages IA-IB1 cervical cancer patients
      undergoing preoperative SPECT/CT for SLN detection were analysed. RESULTS: Forty
      one patients were included. A 100% SLN detection rate was achieved when a
      combined technique (radiotracer and blue dye) was used. At least one SLN was
      clearly visualized by SPECT/CT in 39 of 41 patients (95%) and full anatomic
      concordance with intraoperative anatomical location of SLN was found in 37 of the
      39 patients with at least one SLN identified by SPECT/CT (95%). Location of
      removed SLN included the external and internal iliac area in 88% patients, the
      common iliac area in 10.5%, and the inframesenteric para-aortic area in 1.5%. No
      SLN was found in the infrarenal para-aortic region. Lymph node involvement was
      identified in 5 patients (12.1%). SLN correctly predicted lymph node involvement
      in all node-positive patients. However, SPECT/CT failed to identify 1 of the 5
      metastatic SLN. DISCUSSION: SPECT/CT accurately detected preoperative SLN
      topography and enhanced diagnostic sensitivity of SLN imaging, improving surgical
      approach to patients with cervical cancer staging. Diagnostic quality of anatomic
      landmarks of CT images of SPECT/CT could be further improved by the use of
      contrast injected CT.

PMID- 20822804
TI  - Identification of a patient group at low risk for parametrial invasion in early
      stage cervical cancer.
AB  - AIM: Using parameters obtained from magnetic resonance imaging (MRI), we
      constructed a prediction model for parametrial invasion (PMI) of cervical cancer
      and validated the model in different sets of patients. PATIENTS AND METHODS:
      Retrospectively, 251 patients with cervical cancer stages IA2-IIA, who had
      received a radical hysterectomy, were assigned to training and validation
      cohorts. After the development of the scoring index using logistic coefficient
      analysis, the performance of the prediction model was assessed using independent
      validation sets. RESULTS: In the training cohort (n = 167), multivariate analysis
      indicated that the patient's stage, the cephalocaudal tumor diameter measured by
      MRI, and finding of PMI as obtained by MRI were independent predictors of PMI (P
      = 0.010, < 0.001, and 0.020, respectively). These predictors were internally
      validated by a rigorous bootstrapping method with statistical significance. The
      scoring index was created based on logistic coefficients, and the maximal score
      yielding a negative likelihood ratio less than 0.05 was selected as a cutoff. The
      cutoff was translated into the following criteria identifying a very low-risk
      group for PMI: (1) FIGO stage IA2-IB1, (2) no MRI finding suggesting PMI, and (3)
      cephalocaudal tumor diameter less than 1.0 cm by MRI. The negative predictive
      value (NPV) was 98.5% (95% confidence interval [CI]=91.7% to 100%). In the
      external validation cohort (n = 84), the NPV was 100% (95% CI = 90% to 100%).
      CONCLUSION: The current prediction model showed reliable performance for the
      identification of patients at low risk for PMI. It may be useful for
      stratification of patients and evaluation of results in future trials.

PMID- 20822805
TI  - What is the role of neoadjuvant chemotherapy in advanced endometrial cancer?

PMID- 20822806
TI  - Expression of CYP450-2E1 and formation of 2,3-epoxymethacrylic acid (2,3-EMA) in
      human oral cells exposed to dental materials.
AB  - OBJECTIVES: Methacrylate-based (co)monomers released from dental composites can
      be, metabolized in vivo to methacrylic acid (MA). MA can be further oxidized to
      the toxic 2,3-epoxymethacrylic acid (2,3-EMA) by cytochrome P450 (CYP450)
      enzymes. The subform CYP450-2E1, can metabolize xenobiotics with low-molecular
      weight to epoxides. Oral cells are highly exposed to (co)monomers released from
      composites. Therefore in this study the, expression of CYP450-2E1 in human oral
      (and other) cells was investigated as well as the formation of 2,3-EMA in cells
      exposed to MA. METHODS: Following human oral cells were used: human gingiva
      fibroblasts (HGF), human pulp fibroblasts (HPF), and human tumor buccal
      keratinocytes (SqCC/Y1). As negative control V79 cells without CYP450-2E1
      expression were used. As positive controls V79 cells with CYP450-2E1 expression
      (V79-CYP450-2E1) and pooled human liver microsomes were used. The expression of
      CYP450-2E1 in cells was analyzed with the real-time polymerase chain reaction (RT
      PCR). 2,3-EMA was quantified by the use of the method of gas chromatography/mass
      spectrometry (GC/MS). RESULTS: The highest expression of CYP450-2E1 was found in
      human liver microsomes, followed by SqCC/Y1 cells, V79-CYP450-2E1 cells, HGF, and
      HPF. The highest amount of 2,3-EMA (MUmol/L; mean+/-SEM, n=3) was found in human
      liver microsomes (5.0+/-1.0), followed by SqCC/Y1 cells (2.5+/-0.8), V79-CYP450
      2E1 cells (1.5+/-0.6), HPF (0.3+/-0.3), and HGF (0.2+/-0.2). SIGNIFICANCE: It is
      concluded that the formation of the toxic epoxide 2,3-EMA, as intermediate in the
      metabolism of dental materials, can occur also in human oral cells which can
      express the CYP450-2E1 enzyme system.

PMID- 20822807
TI  - Antiphospholipid syndrome.
AB  - The antiphospholipid syndrome causes venous, arterial, and small-vessel
      thrombosis; pregnancy loss; and preterm delivery for patients with severe pre
      eclampsia or placental insufficiency. Other clinical manifestations are cardiac
      valvular disease, renal thrombotic microangiopathy, thrombocytopenia, haemolytic
      anaemia, and cognitive impairment. Antiphospholipid antibodies promote activation
      of endothelial cells, monocytes, and platelets; and overproduction of tissue
      factor and thromboxane A2. Complement activation might have a central
      pathogenetic role. Of the different antiphospholipid antibodies, lupus
      anticoagulant is the strongest predictor of features related to antiphospholipid
      syndrome. Therapy of thrombosis is based on long-term oral anticoagulation and
      patients with arterial events should be treated aggressively. Primary
      thromboprophylaxis is recommended in patients with systemic lupus erythematosus
      and probably in purely obstetric antiphospholipid syndrome. Obstetric care is
      based on combined medical-obstetric high-risk management and treatment with
      aspirin and heparin. Hydroxychloroquine is a potential additional treatment for
      this syndrome. Possible future therapies for non-pregnant patients with
      antiphospholipid syndrome are statins, rituximab, and new anticoagulant drugs.

PMID- 20822808
TI  - Emotional abuse: a neglected dimension of partner violence.

PMID- 20822809
TI  - Violence against women by their intimate partner during pregnancy and postnatal
      depression: a prospective cohort study.
AB  - BACKGROUND: Partner violence against women is common during pregnancy and might
      have an adverse effect on the mental health of women after delivery. We aimed to
      investigate the association of postnatal depression with psychological, physical,
      and sexual violence against women by their intimate partners during pregnancy.
      METHODS: In a prospective cohort study undertaken in Recife, northeastern Brazil,
      between July, 2005, and December, 2006, we enrolled pregnant women (aged 18-49
      years) in their third trimester of pregnancy who were attending primary health
      care clinics. The women were interviewed during pregnancy and after delivery. The
      form of partner violence in pregnancy was assessed with a validated
      questionnaire, and the Edinburgh postnatal depression scale was used to measure
      postnatal depression. Associations were estimated with odds ratios (ORs),
      adjusted for confounding factors contributing to the association between
      postnatal depression and intimate partner violence. FINDINGS: 1133 pregnant women
      were eligible for inclusion in the study, of whom 1045 had complete data for all
      variables and were included in the analysis. 270 women (25.8%, 95% CI 23.2-28.6)
      had postnatal depression. The most common form of partner violence was
      psychological (294 [28.1%, 25.4-31.0]). Frequency of psychological violence
      during pregnancy was positively associated with occurrence of postnatal
      depression, and although this association was attenuated after adjustment, women
      reporting the highest frequency of psychological violence were more likely to
      have postnatal depression even after adjustment (adjusted OR 2.29, 95% CI 1.15
      4.57). Women who reported physical or sexual violence in pregnancy were more
      likely to develop postnatal depression (OR 3.28, 2.29-4.70), but this association
      was substantially reduced after adjustment for psychological violence and
      confounding factors. INTERPRETATION: Psychological violence during pregnancy by
      an intimate partner is strongly associated with postnatal depression,
      independently of physical or sexual violence. This finding has important policy
      implications since most social policies focus on prevention and treatment of
      physical violence. FUNDING: Departamento de Ciencia e Tecnologia da Secretaria de
      Ciencia, Tecnologia, e Insumos Estrategicos, and Conselho Nacional de
      Desenvolvimento Cientifico e Tecnologico (Brazil).

PMID- 20822810
TI  - EMF directive still poses a risk to MRI research in Europe.

PMID- 20822812
TI  - The restoration of full-thickness cartilage defects with BMSCs and TGF-beta 1
      loaded PLGA/fibrin gel constructs.
AB  - Poly(lactide-co-glycolide) (PLGA) sponge was filled with fibrin gel, bone marrow
      mesenchymal stem cells (BMSCs) and transforming growth factor-beta1 (TGF-beta1)
      to obtain a construct for cartilage restoration in vivo. The PLGA sponge lost its
      weight steadily in vitro, but degraded much faster in the construct of
      PLGA/fibrin gel/BMSCs implanted in the full-thickness cartilage defects. The in
      vivo degradation of the fibrin gel inside the construct was prolonged to 12 wk
      too. The CM-DiI labeled allogenic BMSCs were detectable after transplantation
      (implantation) into the defects for 12 wk by small animal in vivo fluorescence
      imaging and confocal laser scanning microscopy. In vivo repair experiments were
      firstly performed by implantation of the PLGA/fibrin gel/BMSCs and PLGA/BMSCs
      constructs into full-thickness cartilage defects (3 mm in diameter and 4 mm in
      depth) of New Zealand white rabbits for 12 wk. The defects implanted with the
      PLGA/fibrin gel/BMSCs constructs were filled with cartilage-like tissue
      containing collagen type II and glycosaminoglycans (GAGs), while those by the
      PLGA/BMSCs constructs were filled with fibrous-like tissues. To repair the
      defects of larger size (4 mm in diameter), addition of growth factors was
      mandatory as exemplified here by further loading of TGF-beta1. Implantation of
      the PLGA/fibrin gel/BMSCs/TGF-beta1 constructs into the full-thickness cartilage
      defects for 12 wk resulted in full restoration of the osteochondral tissue. The
      neo-cartilage integrated well with its surrounding cartilage and subchondral
      bone. Immunohistochemical and GAGs staining confirmed the similar distribution of
      collagen type II and GAGs in the regenerated cartilage as that of hyaline
      cartilage. The quantitative reverse transcription-polymerase chain reaction (qRT
      PCR) revealed that the cartilage special genes were significantly up-regulated
      compared with those of the TGF-beta1 absent constructs.

PMID- 20822813
TI  - Differentially expressed microRNAs regulate plasmacytoid vs. conventional
      dendritic cell development.
AB  - microRNAs have emerged as a novel layer of regulation of cellular development and
      function, including cells of the immune system. microRNA expression profiles and
      function of several microRNAs have been elucidated in granulocyte macrophage
      colony-stimulating factor derived dendritic cells (GM-CSF DC). In this study we
      determined the microRNA expression profile from plasmacytoid DC (pDC) and
      conventional DC (cDC) generated in murine FMS-related tyrosine kinase 3 ligand
      (Flt3L) bone marrow culture. We observed distinct miRNA expression signatures in
      these two different DC subsets and found that pDC were closer related to CD4(+) T
      cells than to cDC. Expression of a selected subset of microRNAs was also compared
      between cDC and GM-CSF DC. Furthermore, we show that inhibition of two
      differentially expressed microRNAs, miR-221 and miR-222, during differentiation
      resulted in skewed pDC/cDC ratios. Among the confirmed or potential targets for
      miR-221 and miR-222 are c-Kit, p27(kip1) and E2-2. While c-Kit is expressed by DC
      progenitors and p27(kip1) is a cell cycle regulator, E2-2 does transcriptionally
      regulate pDC development. Our data demonstrate that microRNAs can influence Flt3
      driven DC differentiation.

PMID- 20822811
TI  - Incorporation of active DNA/cationic polymer polyplexes into hydrogel scaffolds.
AB  - The effective and sustained delivery of DNA and siRNAs locally would increase the
      applicability of gene therapy in tissue regeneration and cancer therapy. One
      promising approach is to use hydrogel scaffolds to encapsulate and deliver
      nucleotides in the form of nanoparticles to the disease sites. However, this
      approach is currently limited by the inability to load concentrated and active
      gene delivery nanoparticles into the hydrogels due to the severe nanoparticle
      aggregation during the loading process. Here, we present a process to load
      concentrated and un-aggregated non-viral gene delivery nanoparticles, using
      DNA/polyethylene imine (PEI) polyplexes as an example, into neutral polyethylene
      glycol (PEG), negatively charged hyaluronic acid (HA) and protein fibrin
      hydrogels crosslinked through various chemistries. The encapsulated polyplexes
      are highly active both in vitro and in vivo. We believe this process will
      significantly advance the applications of hydrogel scaffold mediated non-viral
      gene delivery in tissue regeneration and cancer therapy.

PMID- 20822814
TI  - Cognitive behavioral analysis system of psychotherapy versus interpersonal
      psychotherapy for early-onset chronic depression: a randomized pilot study.
AB  - BACKGROUND: The only psychotherapy specifically designed and evaluated for the
      treatment of chronic depression, the Cognitive Behavioral Analysis System of
      Psychotherapy (CBASP), has never been directly compared to another depression
      specific psychological method. METHODS: Thirty patients with early-onset chronic
      depression were randomized to 22 sessions of CBASP or Interpersonal Psychotherapy
      (IPT) provided in 16 weeks. Primary outcome was the score on the 24-item Hamilton
      Rating Scale for Depression (HRSD) assessed posttreatment by an independent
      blinded evaluator. Secondary endpoints were, among others, remission (HRSD<=8)
      rates and the Beck Depression Inventory (BDI). The study included a prospective
      naturalistic 12-month follow-up. RESULTS: Intent-to-treat analyses of covariance
      (ANCOVA) revealed that there was no significant difference in posttreatment HRSD
      scores between the CBASP and the IPT condition, but in self-rated BDI scores. We
      found significantly higher remission rates in the CBASP (57%) as compared to the
      IPT (20%) group. One year posttreatment, no significant differences were found in
      the self-reported symptom level (BDI) using ANCOVA. LIMITATIONS: The study used
      only a small sample size and no placebo control. The generalizability of the
      results may be limited to patients with a preference for psychological treatment.
      CONCLUSIONS: While the primary outcome was not significant, secondary measures
      showed relevant benefits of CBASP over IPT. We found preliminary evidence that in
      early-onset chronic depression, an approach specifically designed for this
      patient population was superior to a method originally developed for the
      treatment of acute depressive episodes. Long-term results suggest that
      chronically depressed patients may need extended treatment courses.

PMID- 20822815
TI  - Effects of two commercially available immunostimulants on leukocyte function of
      foals following ex vivo exposure to Rhodococcus equi.
AB  - The objective of this study was to determine the effect of immunostimulants on
      neutrophil, macrophage, and lymphocyte function following ex vivo exposure to
      Rhodococcus equi. Eighteen foals were randomly assigned to one of 3 treatment
      groups. Treatment consisted of inactivated Propionibacterium acnes (PA),
      inactivated parapoxvirus ovis (PPVO), or saline (control) administered on days 0
      (7 days of age), 2, and 8. Bronchoalveolar lavage (BAL) fluid and blood were
      collected on days 0 (baseline), 12, 24 and 36. Intracellular replication of R.
      equi in macrophages, cytokine induction by R. equi-infected macrophages,
      phagocytic and oxidative burst activity of neutrophils, lymphoproliferative
      responses, and cytokine induction of proliferating lymphocytes were measured.
      Neutrophils from foals treated with PPVO had significantly greater ability to
      phagocytize R. equi and undergo oxidative burst on day 12 and day 24 compared to
      baseline values. On day 24, foals treated with PPVO had significantly greater
      phagocytosis and oxidative burst than foals treated with PA. Treatment with PA
      resulted in significantly less intracellular proliferation of R. equi within
      monocyte-derived macrophages on day 12 compared to control foals. The ability of
      R. equi to replicate in BAL macrophages decreased significantly (P=0.005) with
      time with lower replication in BAL macrophages of older foals compared to younger
      foals, regardless of treatment. On day 12, TNF-alpha induction in monocyte
      derived macrophages and IL-12 p40 induction in BAL macrophages infected with R.
      equi was significantly higher in foals treated with PPVO than in controls.
      Lymphoproliferative responses and IFN-gamma induction were not significantly
      different between groups.

PMID- 20822816
TI  - Nasal chondromesenchymal hamartoma in children with pleuropulmonary blastoma--A
      report from the International Pleuropulmonary Blastoma Registry registry.
AB  - OBJECTIVES: Nasal chondromesenchymal hamartoma (NCMH) is an uncommon chondro
      stromal tumor of the nasal cavity and paranasal sinuses in infancy and childhood.
      Pleuropulmonary blastoma (PPB) is also a rare malignancy of lung and pleura in
      childhood and is the sentinel disease of an important familial tumor and
      dysplasia syndrome. This study identified NCMH in PPB patients. METHODS: The
      International PPB Registry collects cases of PPB using central pathology review
      and evaluation of clinical records. The Registry also evaluates PPB literature.
      Examples of NCMH occurring with PPB were identified. Clinical records, digital
      radiography and pathologic specimens of PPB-associated NCMH cases were analyzed.
      RESULTS: Among approximately 625 cases of PPB, four children developed NCMH.
      These cases are among 28 total reported NCMH cases. NCMH presented with sinonasal
      congestion and visible polypoid nasal masses and were diagnosed from ages 7 to 15
      years, similar to older reported NCMH cases. NCMH involved the nasal cavity,
      paranasal sinuses and upper nasopharynx, was bilateral in three children and
      locally recurrent in one. In two children, NCMH had the characteristic pathologic
      spectrum of immature nodules of cartilage surrounded by spindle cell stroma,
      whereas the other two NCMH displayed mature chondroid nodules and a less varied
      fibrous stroma. NCMH was not identified in family members with PPB. CONCLUSIONS:
      NCMH developing in four children with PPB indicates that NCMH is part of the
      heredofamilial disease complex associated with PPB. Otorhinolaryngologists and
      pediatric oncologists should be aware that these two rare conditions occur
      together and that affected patients may have a familial predisposition to
      childhood malignant and dysplastic disease.

PMID- 20822817
TI  - Ultrastructural effects on gill, muscle, and gonadal tissues induced in zebrafish
      (Danio rerio) by a waterborne uranium exposure.
AB  - Experiments on adult zebrafish (Danio rerio) were conducted to assess
      histopathological effects induced on gill, muscle, and gonadal tissues after
      waterborne uranium exposure. Although histopathology is often employed as a tool
      for the detection and assessment of xenobiotic-mediated effects in aquatic
      organisms, few studies have been dedicated to the investigation of
      histopathological consequences of uranium exposure in fish. Results showed that
      gill tissue architecture was markedly disrupted. Major symptoms were alterations
      of the secondary lamellae epithelium (from extensive oedema to desquamation),
      hyperplasia of chloride cells, and breakdown of the pillar cell system. Muscle
      histology was also affected. Degeneration and disorganization of myofibrillar
      sarcomeric pattern as well as abnormal localization of mitochondria within muscle
      and altered endomysial sheaths were observed. Morphological alterations of
      spermatozoa within the gonadal tissue were also noticed. This study demonstrated
      that uranium exposure induced a variety of histological impairments in fish,
      supporting environmental concerns when uranium contaminates aquatic systems.

PMID- 20822818
TI  - Surgery for valve disease in young people--beyond morbidity and mortality.

PMID- 20822819
TI  - On the cognitive processes underlying contextual interference: Contributions of
      practice schedule, task similarity and amount of practice.
AB  - This experiment was designed to assess the combined influence of practice
      schedule (blocked or random), task similarity (similar or dissimilar), and amount
      of practice on motor learning. Participants were required to perform three
      movement times (200, 350, and 500ms) in a blocked or random schedule while
      pointing towards the target located in the front direction in the similar
      condition, or towards three targets (left, front, and right) in the dissimilar
      condition. In each condition, participants completed 99 or 297 acquisition trials
      before a delayed retention test similar for all participants. Results indicated a
      contextual interference (CI) effect due to the schedule of practice following 297
      trials for similar task variations: blocked schedule tended to produce better
      performance early in practice; random schedule enhanced learning for a larger
      amount of practice. However, when participants experienced dissimilar task
      variations, no blocked-random difference was found whatever the amount of
      practice. This suggests that task similarity is a learning variable that
      modulates the CI effect. Our findings argue for the evidence that the intertask
      processing evoked by random schedule is not sufficient to improve learning and
      that there may be a ceiling effect on retention performance due to the extent of
      additional intertask processing.

PMID- 20822821
TI  - Treatment regimens with insulin analogues and haemoglobin A1c target of <7% in
      type 2 diabetes: a systematic review.
AB  - We conducted a systematic review of randomized controlled trials that evaluated
      the effectiveness of insulin regimens (basal, biphasic, prandial, and basal
      bolus) with insulin analogues to reach the haemoglobin A1c target of <7% in
      patients with type 2 diabetes. We identified 48 trials, with 85 arms and 30,588
      patients. There were 38 arms using basal insulin, with 17,588 patients, and a
      primary outcome of 41.4% (95% CI=35.6-47.4%); 26 arms using biphasic insulin,
      with 9237 patients, and a primary outcome of 46.5% (40.8-52.3%); 9 arms using
      prandial insulin, with 1605 patients, and a primary outcome of 39.6% (95% CI,
      28.6-51.3%); and 12 arms using basal-bolus insulin, with 2114 patients, and a
      primary outcome of 53.9% (43.5-64). The high heterogeneity was related, in part,
      to first time insulin use, final insulin dose, and use of oral drug. The overall
      incidence of hypoglycaemia ranged from 0 to 4.71 events/patient/30 days; weight
      gain ranged from 1.75 kg for basal to 3 kg for biphasic insulin. The HbA1c target
      of <7% can be achieved in a percentage of type 2 diabetic patients ranging from
      40% to 54% depending on the particular insulin regimen.

PMID- 20822820
TI  - C-reactive protein as an outcome predictor for percutaneous transluminal
      angioplasty in diabetic patients with peripheral arterial disease and infected
      foot ulcers.
AB  - AIM: Although percutaneous transluminal angioplasty (PTA) is an effective
      therapeutic procedure for critical limb ischemia, several clinical factors can
      influence the outcome of PTA for peripheral arterial disease (PAD). The aim of
      this study is to identify the outcome predictors of PTA in infected diabetic foot
      patients with PAD. METHODS: Eighty-five diabetic patients with a total of 90
      infected limbs treated by PTA participated in this study. Patients were initially
      admitted for infected foot ulcers and were later diagnosed with PAD. Even though
      all patients underwent successful PTA within 15 days of admission, limb salvage
      was successful in 66 cases while 24 underwent subsequent amputation. The clinical
      characteristics and laboratory variables of both groups before PTA were compared
      and analyzed. RESULTS: Significantly higher level of C-reactive protein (CRP) was
      observed in the major amputation group before PTA. The cutoff value via receiver
      operating characteristic curve was 50mg/L (81.8% specificity, 70.7% sensitivity).
      Multivariate logistic regression analysis revealed that CRP levels may serve as
      valuable marker in determining a successful outcome. CONCLUSION: Reduced CRP
      levels (<50mg/L), which indicates a low infection severity, may serve as a major
      predictor of successful PTA outcome in diabetic patients with infected foot
      ulcers.

PMID- 20822822
TI  - Impact of diabetes and hypertension on left ventricular longitudinal systolic
      function.
AB  - BACKGROUND: The assessment of the longitudinal component of left ventricular (LV)
      function is of major clinical importance for the early detection of LV
      contractile impairment. The aim of this study was to compare the impact of
      isolated type-2 diabetes, isolated hypertension, and co-existence of both on LV
      longitudinal systolic performance, with particular focus on their potential
      interaction effect. METHODS: The study population included 163 consecutive
      patients: 84 patients with hypertension, 36 with diabetes, and 43 who have both
      hypertension and diabetes; 70 healthy controls were also recruited. Systolic
      mitral annulus velocity (S(m)) by Tissue Doppler and left atrioventricular plane
      displacement (AVPD) by M-mode were measured in all subjects. RESULTS: AVPD was
      similarly reduced in hypertensives (13.2+/-2.2mm) and diabetics (13.5+/-2.3mm)
      when compared with the controls (15.1+/-2.4mm), and further depressed in diabetic
      hypertensives (11.5+/-3.0mm). Similar results were found for S(m). General linear
      model analysis revealed no significant interaction terms between diabetes and
      hypertension. CONCLUSIONS: Normotensive diabetics and nondiabetic hypertensives
      show comparable depression in LV longitudinal systolic indices when compared with
      age- and gender-matched healthy controls; the co-existence of diabetes and
      hypertension leads to further impairment in LV longitudinal systolic function in
      an additive manner.

PMID- 20822823
TI  - Healthcare utilisation among the Belgian elderly in relation to their socio
      economic status.
AB  - OBJECTIVES: To analyse the association between healthcare utilisation of elderly
      persons (65 and over) in Belgium in terms of contacts with GP or specialist and
      the socio-economic indicators household income, highest educational level within
      the household, and housing tenure. METHODS: A cross-sectional study based on 4494
      non-institutionalised elderly participants in the Belgian Health Interview
      Surveys of 2001 and 2004. Socio-economic gradients in contacts (yes or no) with a
      GP or specialist were explored, based on the socio-behavioural model of Andersen,
      a conceptual framework that includes the most important determinants of
      healthcare utilisation. Three multivariate models were constructed using multiple
      logistic regression. RESULTS: After adjustment for age, sex, health status (self
      assessed health, functional restrictions, and comorbidity), region, and living
      situation, initial differences in contacts with a GP and specialist between the
      different socio-economic groups disappeared among the elderly. On the other hand,
      contacts with a specialist remain dependent on SES in the younger population.
      CONCLUSIONS: Adjustment for the determinants of healthcare utilisation among the
      Belgian elderly nullified the socio-economic gradients in contacts with a GP and
      specialist that initially existed. The results point to a potential link with the
      Belgian social and health policy.

PMID- 20822824
TI  - A rapid review of key strategies to improve the cognitive and social development
      of children in Scotland.
AB  - OBJECTIVES: Inequalities in health and educational outcomes in Scotland show a
      strong and persistent socioeconomic status gradient. Our aims were to provide
      policy-makers with a synthesis of international research evidence that assesses
      the effectiveness of early childhood interventions aimed at equitably promoting
      cognitive and social development and suggest potential areas for action in
      Scotland. METHODS: A rapid review was conducted of review level studies of early
      childhood interventions with outcome measures relating to child cognitive
      language or social-emotional development, subsequent academic and life
      achievement. Websites were searched and interviews were conducted to identify
      relevant interventions, policies and programmes delivered in Scotland. RESULTS: :
      Early childhood intervention programmes can reduce disadvantage due to social and
      environmental factors. Scottish health policy demonstrates a clear commitment to
      early childhood development but much work remains in terms of detail of policy
      implementation, identification of high risk children and families, and early
      childhood monitoring systems. CONCLUSIONS: Programmes should provide a universal
      seamless continuum of care and support from pregnancy through to school entry
      with the intensity of support graded according to need. The current information
      systems in Scotland would be inadequate for monitoring the effects of early
      childhood interventions especially in relation to cognitive-language and social
      emotional development.

PMID- 20822825
TI  - Analysis of multiple linear regression algorithms used for respiratory mechanics
      monitoring during artificial ventilation.
AB  - Many patients undergo long-term artificial ventilation and their respiratory
      system mechanics should be monitored to detect changes in the patient's state and
      to optimize ventilator settings. In this work the most popular algorithms for
      tracking variations of respiratory resistance (R(rs)) and elastance (E(rs)) over
      a ventilatory cycle were analysed in terms of systematic and random errors.
      Additionally, a new approach was proposed and compared to the previous ones. It
      takes into account an exact description of flow integration by volume-dependent
      lung compliance. The results of analyses showed advantages of this new approach
      and enabled to form several suggestions. Algorithms including R(rs) and E(rs)
      dependencies on airflow and lung volume can be effectively applied only at low
      levels of noise present in measurement data, otherwise the use of the simplest
      model with constant parameters is preferable. Additionally, one should avoid
      including the resistance dependence on airflow alone, since this considerably
      destroys the retrieved trace of R(rs). Finally, the estimated cyclic trajectories
      of R(rs) and E(rs) are more sensitive to noise present in pressure than in the
      flow signal, and the elastance traces are estimated more accurately than the
      resistance ones.

PMID- 20822826
TI  - Analysis of wait times and costs during the peri-diagnostic period for non-small
      cell lung cancer.
AB  - PURPOSE: To determine the wait times and healthcare costs around the time of non
      small cell lung cancer (NSCLC) diagnosis for a large, population-based cohort of
      patients. METHODS: Data on baseline demographics, diagnostic and staging tests,
      timelines of investigations, and frequency of physician visits and hospital
      admissions were obtained from a provincial cancer registry and health
      administrative databases for 2852 patients, who were diagnosed with NSCLC from
      1996 to 2000 in Manitoba, Canada. Dates between investigations were used to
      determine wait times surrounding diagnosis and fee codes for physician and
      hospital services were used to estimate costs. RESULTS: The median wait times
      from chest x-ray to chest computed tomography (CT) scan and from CT scan to
      definitive histological diagnosis were 8 (inter-quartile range 1-25) and 18
      (inter-quartile range 3-42) days, respectively. At least 25% of patients waited
      more than 55 days from initial suspicion on chest x-ray to final diagnosis of
      NSCLC. The mean cost per case of NSCLC diagnosis was $6,978 (in Canadian dollars)
      where the majority of expenses was attributed to hospital admissions and repeated
      physician visits before a diagnosis was confirmed. CONCLUSIONS: Despite clinical
      suspicion for NSCLC, a significant number of patients wait more than 8 weeks for
      a definitive diagnosis. Substantial costs are incurred by the Canadian universal
      healthcare system in the months surrounding diagnosis. Establishment of more
      efficient and cost-effective healthcare delivery in the peri-diagnostic time
      period may benefit the system as well as the patients.

PMID- 20822827
TI  - Prognostic implications of hypoxia-inducible factor-1alpha in epidermal growth
      factor receptor-negative non-small cell lung cancer.
AB  - Hypoxia-inducible factor (HIF)-1alpha is a regulatory subunit of HIF-1 that is
      stabilized and activated under hypoxic conditions. In non-small cell lung cancer
      (NSCLC), over-expression of HIF-1alpha has been associated with poor overall
      survival. However, there is conflicting data on the role of HIF-1alpha as a
      prognostic factor. Some studies have demonstrated close association between the
      HIF-1alpha signal pathways and epidermal growth factor receptors (EGFRs). We
      evaluated the prognostic significance of HIF-1alpha expression in 178 NSCLC
      patients using tissue microarray in the context of EGFR gene copy number and
      protein expression status. EGFR gene copy number was evaluated using fluorescent
      in situ hybridization (FISH), and EGFR protein expression was determined using
      immunohistochemistry (IHC). The difference in overall survival (OS) between HIF
      1alpha-positive and HIF-1alpha-negative groups was statistically significant in
      patients with low EGFR gene copy number and negative EGFR expression (log-rank
      test, P = 0.03). In univariate and multivariate analyses, HIF-1alpha was a
      significant worse prognostic factor for OS in patients with low EGFR gene copy
      number and negative EGFR expression (hazard ratio = 2.992; 95% CI, 1.113-8.045; P
      = 0.03 in univariate analysis and hazard ratio = 8.127; 95% CI, 1.874-35.251; P <
      0.01 in multivariate analysis). The results demonstrated that the prognostic
      significance of HIF-1alpha should be validated in the context of EGFR status in
      NSCLC patients, and the gene and protein status of EGFR and HIF-1alpha will be
      important to help select patients most likely to derive the greatest clinical
      benefit from EGFR or HIF-1alpha targeted therapies.

PMID- 20822828
TI  - Enhanced tryptophan degradation in patients with ovarian carcinoma correlates
      with several serum soluble immune activation markers.
AB  - Tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) represents an
      antimicrobial and antitumoral immune effector mechanism, but IDO also suppresses
      T-cell responses and thus can cause immune system failure. Therefore, IDO was
      proposed as an immunoescape mechanism of tumor cells. Compared to healthy
      controls, accelerated tryptophan degradation was observed in the blood of 20
      patients with ovarian carcinoma as is reflected by an increased kynurenine to
      tryptophan ratio (kyn/trp) which allows an estimate of IDO activity. Higher FIGO
      stage but not tumor grading was associated with a higher rate of tryptophan
      degradation. Kyn/trp correlated strongly with concentrations of cytokine IL-6, of
      soluble interleukin-2 receptor-alpha and 75 kDa TNF-alpha receptor and of the
      macrophage marker neopterin (all p<0.001 or p<0.01) but not with TNF-alpha.
      Findings further supports the concept that increased IDO activity in ovarian
      cancer patients relates to immune activation pathways. Accordingly, accelerated
      tryptophan degradation appears to represent an immune escape mechanism. However
      IDO activity is not necessarily a spontaneous activity of ovarian cancer cells
      rather it is elicited by the activated immune system although an additional
      spontaneous activity of tumor cells cannot be ruled out.

PMID- 20822829
TI  - T lymphocytes from malnourished infants are short-lived and dysfunctional cells.
AB  - To investigate T-cell functional molecules and inflammatory cytokines and to
      assess T-cell apoptosis in malnourished infants, 64 infants from undernourished
      women and 28 healthy control infants were recruited to the study. Malnourished
      infants showed a significant decrease in the levels of circulating IL-2 and IL-7
      and increases in the levels of IL-1beta, IL-6, IL-10 and TNF-alpha, as measured
      by flow cytometry. There was a significant reduction in the number of CD3(+) T
      cells and an increase in apoptotic T cells, which was associated with an up
      regulation of CD95 and PD-1 expression on CD3(+) T cells in malnourished compared
      to control infants. Significant reductions were also observed in the
      phosphorylation of AKT and STAT5 and in the expression of CCR7 and CXCR4
      receptors in malnourished children, and these reductions were associated with a
      significant reduction in T-cell migratory capacity to their ligands CCL21 and
      CXCL12, respectively, as measured using an in vitro chemotaxis assay. Taken
      together, these data suggest that lymphocytes from malnourished infants are short
      lived and dysfunctional.

PMID- 20822830
TI  - Significant reduction of laboratory specimen labeling errors by implementation of
      an electronic ordering system paired with a bar-code specimen labeling process.
AB  - STUDY OBJECTIVE: We measure the rate of emergency department (ED) specimen
      processing error reduction after implementation of an electronic physician order
      entry system paired with a bar-coded specimen labeling process. METHODS: A cohort
      pre- and postintervention study was conducted in the ED during a 61-month period
      ending September 2008 in a large urban teaching hospital. Historically,
      laboratory order and requisition processing was done by hand. Interventions
      included implementing an ED-specific electronic documentation and information
      system, which included physician order entry with patient verification through
      bar-coded wristbands and bar-coded specimen labels. The main outcome measure was
      processing error rate, defined as unlabeled/mislabeled/wrong patient specimen or
      requisition. Pre- and postimplementation data were tabulated monthly and compared
      in aggregate by chi(2) test. The contribution of ED error to total institution
      specimen error was also calculated. RESULTS: Of the 724,465 specimens collected
      preintervention, 3,007 (0.42%) were recorded as errors versus 379 errors (0.11%)
      of 334,039 specimens collected postintervention, which represents a 74% relative
      and 0.31% absolute decrease (95% confidence interval 0.28% to 0.32%). The
      proportion of institutional errors contributed by the ED was reduced from 20.4%
      to 11.4%, a 44% relative and 9.0% absolute reduction (95% confidence interval
      7.7% to 10.3%). Subanalysis revealed that the majority of continued errors occur
      when the physician order entry/bar-code system could not be used (eg, blood bank
      or surgical pathology specimens). CONCLUSION: Combining an electronic physician
      order entry with bar-coded patient verification and electronic documentation and
      information system-generated specimen labels can significantly reduce ED specimen
      related errors, with sizable influence on institutional specimen-related errors.
      Continued use of hand labeling and processing for special specimens appears
      inadvisable, though the cost-effectiveness of this intervention has not been
      established.

PMID- 20822831
TI  - First outbreak of methicillin-resistant Staphylococcus aureus USA300 harboring
      the Panton-Valentine leukocidin genes among Japanese health care workers and
      hospitalized patients.
AB  - This report describes the first outbreak of methicillin-resistant Staphylococcus
      aureus USA300 in a general hospital ward in Japan, involving 6 health care
      workers and 4 patients. This report emphasizes the need for health care personnel
      to be alert that methicillin-resistant Staphylococcus aureus harboring Panton
      Valentine leukocidin gene poses a threat for both nosocomial and occupational
      infection.

PMID- 20822833
TI  - Synthesis and anti-tubercular and antimicrobial activities of some 2r,4c-diaryl-3
      azabicyclo[3.3.1]nonan-9-one N-isonicotinoylhydrazone derivatives.
AB  - In this study, seven 2r,4c-diaryl-3-azabicyclo[3.3.1]nonan-9-one N
      isonicotinoylhydrazones 8-14 were synthesized. The structure and stereochemistry
      of these compounds were established by IR and NMR spectral data. The purities
      were checked by elemental analysis. The synthesized compounds adopt twin-chair
      conformation with equatorial orientations of the aryl groups. The compounds were
      evaluated for their in vitro anti-tubercular and antimicrobial activities. The
      initial screen was conducted against Mycobacterium tuberculosis H(37)Rv (ATTCC
      27294) and INH-TB by luciferase reporter phage assay method. All the synthesized
      compounds showed very good activity against MTB and INH-TB. Though all the
      compounds showed good antimicrobial activity only 11 (Ar = p-chlorophenyl), 12
      (Ar = p-fluorophenyl), 13 (Ar = m-chlorophenyl) and 14 (Ar = m-methoxyphenyl)
      exhibited activity against all the tested (bacterial and fungal) microorganisms.
      The results suggest that the formation of hydrogen bonds may play a significant
      role in drug action.

PMID- 20822834
TI  - Only connect . . . a response (connected!).

PMID- 20822835
TI  - Involvement of inpatient mental health clients in the practical training and
      assessment of mental health nursing students: Can it benefit clients and
      students?
AB  - Even though the central position of the client has been recognized in psychiatric
      nursing education, the client is seldom formally involved in the feedback
      provided to students during practical training. This research paper focuses on
      three questions: (1) What conditions support the gathering of meaningful client
      feedback to enhance the student's learning process and client's wellbeing? (2)
      Does the use of the practical model for client feedback lead to positive
      experiences, and if so, under what conditions? (3) To what extent is a client's
      feedback on the student's work performance, consistent with feedback from the
      mentor (nurse from the ward), the teacher and the student? Based on a literature
      review, participatory observation and contacts with experts, a practical model
      was developed to elicit client feedback. Using this model in two psychiatric
      inpatient services, clients were actively and formally involved in providing
      feedback to four, final year psychiatric nursing students. Clients, nurses,
      teachers and students were interviewed and data were analysed using a qualitative
      explorative research approach. Analyses revealed that client feedback becomes
      meaningful in a safe environment created by the psychiatric nurse. Client
      feedback generates a learning effect for the student and supports the student's
      recognition of the value and vulnerability of the psychiatric client.

PMID- 20822836
TI  - A biomechanical analysis of trunk and pelvis motion during gait in subjects with
      knee osteoarthritis compared to control subjects.
AB  - BACKGROUND: Trunk lean over the stance limb during gait has been linked to a
      reduction in the knee adduction moment, which is associated with joint loading.
      We examined differences in knee adduction moments and frontal plane trunk lean
      during gait between subjects with knee osteoarthritis and a control group of
      healthy adults. METHODS: Gait analysis was performed on 80 subjects (40
      osteoarthritis). To define lateral trunk lean two definitions were used. The line
      connecting the midpoint between two reference points on the pelvis and the
      midpoint between the acromion processes was projected onto the lab frontal plane
      and the pelvis frontal plane. Pelvic tilt was also measured in the frontal plane
      as the angle between the pelvic and lab coordinate systems. Angles were
      calculated across the stance phase of gait. We analyzed the data, (i) by
      extracting discrete parameters (mean and peak) waveform values, and (ii) using
      principal component analysis to extract shape and magnitude differences between
      the waveforms. FINDINGS: Osteoarthritis subjects had a higher knee adduction
      moment than the control group (alpha=0.05). Although the discrete parameters for
      trunk lean did not show differences between groups, principal component analysis
      did detect characteristic waveform differences between the control and
      osteoarthritis groups. INTERPRETATION: A thorough biomechanical analysis revealed
      small differences in the pattern of motion of the pelvis and the trunk between
      subjects with knee osteoarthritis and control subjects; however these differences
      were only detectable using principal component analysis.

PMID- 20822837
TI  - Influence of arsenic stress on synthesis and localization of low-molecular-weight
      thiols in Pteris vittata.
AB  - The roles of low-molecular-weight thiols (LMWTs), such as glutathione and
      phytochelatins, in arsenic (As) tolerance and hyperaccumulation in Pteris vittata
      an As-hyperaccumulator fern remain to be better understood. This study aimed to
      thoroughly characterize LMWT synthesis in P. vittata to understand the roles
      played by LMWTs in As tolerance and hyperaccumulation. LMWT synthesis in P.
      vittata was induced directly by As, and not by As-mediated oxidative stress.
      Expression of PvECS2, one of the putative genes of gamma-glutamylcysteine
      synthetase (gammaECS), increases in P. vittata shoots at 48h after the onset of
      As exposure, almost corresponding to the increase in the concentrations of gamma
      glutamylcysteine and glutathione. Furthermore, localization of As showed similar
      trends to those of LMWTs in fronds at both whole-frond and cellular levels. This
      study thus indicates the specific contribution of LMWTs to As tolerance in P.
      vittata. gammaECS may be responsible for the As-induced enhancement of LMWT
      synthesis.

PMID- 20822838
TI  - Compartmentation of metals in foliage of Populus tremula grown on soils with
      mixed contamination. I. From the tree crown to leaf cell level.
AB  - In order to achieve efficient phytoextraction of heavy metals using trees, the
      metal allocation to aboveground tissues needs to be characterised. In his study,
      the distribution of heavy metals, macro- and micronutrients and the metal micro
      localisation as a function of the leaf position and heavy metal treatment were
      analysed in poplars grown on soil with mixed metal contamination. Zinc was the
      most abundant contaminant in both soil and foliage and, together with cadmium,
      was preferentially accumulated in older foliage whereas excess copper and lead
      were not translocated. Changes in other element concentrations indicated an
      acceleration in aging as a consequence of the metal treatment. Excess zinc was
      irregularly accumulated inside leaf tissues, tended to saturate the veins and was
      more frequently stored in cell symplast than apoplast. Storage compartments
      including metabolically safe and sensitive subcellular sites resulted in sizable
      metal accumulation as well as stress reactions.

PMID- 20822839
TI  - Advancing health equity in the global marketplace: how human rights can help.
AB  - The WHO Commission on Social Determinants of Health (CSDH) ascribed health
      disparities within and between countries to "a toxic combination of poor social
      policies and programmes, unfair economic arrangements, and bad politics." This
      article analyzes the relevance of the international human rights framework (IHRF)
      to the Commission's goal of reducing health disparities with reference to both
      social scientific and legal scholarship. We begin with an overview of the IHRF,
      demonstrating its potential as a challenge to the normative foundations of the
      emerging global economic order. We then survey the research literature on
      mechanisms to ensure accountability for realization of health-related rights,
      emphasizing the potential effectiveness of making human rights enforceable
      through the courts, and the special need for mechanisms to hold countries and
      international institutions accountable for obligations related to the human right
      to health. We conclude by identifying three key directions for further research,
      policy and advocacy: comparative human rights litigation, specifically the
      willingness of courts to address broad policy and budgetary issues; the
      conditions under which governments legislate or constitutionalize economic and
      social rights; and how rich, powerful countries affect economic and social rights
      outside their borders.

PMID- 20822840
TI  - The public health critical race methodology: praxis for antiracism research.
AB  - The number of studies targeting racial health inequities and the capabilities for
      measuring racism effects have grown substantially in recent years. Still, the
      need remains for a public health framework that moves beyond merely documenting
      disparities toward eliminating them. Critical Race Theory (CRT) has been the
      dominant influence on racial scholarship since the 1980s; however, its
      jurisprudential origins have, until now, limited its application to public health
      research. To improve the ease and fidelity with which health equity research
      applies CRT, this paper introduces the Public Health Critical Race praxis (PHCR).
      PHCR aids the study of contemporary racial phenomena, illuminates disciplinary
      conventions that may inadvertently reinforce social hierarchies and offers tools
      for racial equity approaches to knowledge production.

PMID- 20822841
TI  - Longing to belong: social inclusion and wellbeing among youth with refugee
      backgrounds in the first three years in Melbourne, Australia.
AB  - For young people with refugee backgrounds, establishing a sense of belonging to
      their family and community, and to their country of resettlement is essential for
      wellbeing. This paper describes the psychosocial factors associated with
      subjective health and wellbeing outcomes among a cohort of 97 refugee youth (aged
      11-19) during their first three years in Melbourne, Australia. The findings
      reported here are drawn from the Good Starts Study, a longitudinal investigation
      of settlement and wellbeing among refugee youth conducted between 2004 and 2008.
      The overall aim of Good Starts was to identify the psychosocial factors that
      assist youth with refugee backgrounds in making a good start in their new
      country. A particular focus was on key transitions: from pre-arrival to
      Australia, from the language school to mainstream school, and from mainstream
      school to higher education or to the workforce. Good Starts used a mix of both
      method and theory from anthropology and social epidemiology. Using standardized
      measures of wellbeing and generalised estimating equations to model the
      predictors of wellbeing over time, this paper reports that key factors strongly
      associated with wellbeing outcomes are those that can be described as indicators
      of belonging - the most important being subjective social status in the broader
      Australian community, perceived discrimination and bullying. We argue that
      settlement specific policies and programs can ultimately be effective if embedded
      within a broader socially inclusive society - one that offers real opportunities
      for youth with refugee backgrounds to flourish.

PMID- 20822842
TI  - Management of the infected temporomandibular joint total joint prosthesis.
AB  - PURPOSE: Patients with specific temporomandibular joint (TMJ) conditions and
      pathology may benefit from TMJ reconstruction by use of total joint prostheses. A
      potential risk to patients receiving TMJ total joint prostheses is infection. The
      purpose of this study was to present our experience in treating infected TMJ
      total joint prostheses over a 12-year period, as well as the protocol we have
      developed to manage acute infections and the protocol we follow for chronic
      infections of TMJ total joint prostheses. PATIENTS AND METHODS: This
      retrospective study evaluated the records of 316 consecutive patients (290 female
      and 26 male patients) who had TMJ reconstruction from 1997 to 2009 by 1 surgeon,
      using patient-fitted TMJ Concepts total joint prostheses (TMJ Concepts, Ventura,
      CA), with a total of 579 prostheses placed, to determine the occurrence and
      management methods of postoperative infections. Postoperative infections
      involving the TMJ prostheses developed in 8 of 316 patients (2.5%) and 9 of 579
      prostheses (1.6%): 7 patients unilaterally and 1 patient bilaterally. Patients
      were divided into 2 groups: group 1 (n = 5) had acute infections in 6 joints and
      group 2 (n = 3) had chronic infections in 3 joints. Patient 5 began in group 1
      but was transferred to group 2. One patient with Munchausen syndrome and self
      induced infections was eliminated from the study. Patients were treated by our
      protocol for management of acute or chronic infections. RESULTS: In group 1 (n =
      5) the onset of infection symptoms averaged 12 days after surgery (range, 5-24
      days). The time from onset of symptoms to surgical intervention was 3.4 days
      (range, 2-5 days). We found that 4 of 5 patients (80%) and 5 of 6 joints (83%)
      were successfully treated with retention of the prostheses. Patient 5 varied from
      the protocol and maintained a chronic infection of her right TMJ prosthesis that
      transferred her to group 2. In group 2 (n = 3) all 3 patients (including patient
      5) had chronic infections with draining fistulas that were successfully treated
      by the chronic infection protocol including prosthesis removal and replacement.
      CONCLUSIONS: TMJ total joint prostheses can become infected. The earlier the
      diagnosis is made and the acute infection protocol initiated (within 2-5 days),
      the greater the chance of salvage of the prosthesis. For chronic infections, the
      treatment protocol has likewise been very successful, but it does require 2
      surgical stages for removal and replacement of the prosthesis. Management of
      infected total joint prosthesis can be challenging, but with aggressive treatment
      following the appropriate protocol, infected prostheses can be successfully
      managed.

PMID- 20822843
TI  - Management of facial nerve schwannoma in the accessory parotid region.

PMID- 20822844
TI  - Temporomandibular joint-related symptoms as initial presentation of lung
      carcinoma in a patient with Takayasu's arteritis.

PMID- 20822845
TI  - Oral and maxillofacial surgery and chronic painful temporomandibular disorders--a
      systematic review.
AB  - PURPOSE: To provide a systematic review of the best available research literature
      investigating the relation of oral and maxillofacial surgical procedures to the
      onset or relief of chronic painful temporomandibular disorder (TMD). MATERIALS
      AND METHODS: A comprehensive review of the databases CINAHL, Cochrane Library,
      Embase, Medline, NHS Evidence--Oral Health, PsycINFO, Web of Knowledge, and
      MetaLib was undertaken by 2 authors (P.S., M.H.) up to June 2009 using search
      terms appropriate to establishing a relation between orofacial surgical
      procedures and TMD. The search was restricted to English-language publications.
      RESULTS: Of the 1,777 titles reviewed, 35 articles were critically appraised but
      only 32 articles were considered eligible. These were observational studies that
      fell into 2 groups; 9 were seeking to establish a surgical cause for TMD. Of
      these, only 2 of a series of 3 claimed that there was a significant link, but
      this claim was based on weak data (health insurance records) and was abandoned in
      a subsequent report. Twenty-three studies were seeking to achieve relief by
      orthognathic surgical intervention. These were also negative overall, with 7
      articles showing varying degrees of mostly nonsignificant improvement, whereas 16
      showed no change or a worse outcome. No published report on the putative effect
      of implant insertion was found. CONCLUSION: These apparently contradictory
      approaches underline a belief that oral surgical trauma or gross malocclusion has
      a causative role in the onset of TMD. However, there was no overall evidence of a
      surgical causal etiology or orthognathic therapeutic value. This review
      emphasizes that it is in the patients' best interest to carry out prospective
      appropriately controlled randomized trials to clarify the situation.

PMID- 20822846
TI  - Clarifications to the consensus document on the diagnosis, treatment and
      prevention of tuberculosis.

PMID- 20822847
TI  - Younger maternal age (at initiation of childbearing) and recurrent perinatal
      mortality.
AB  - OBJECTIVE: To assess whether young maternal age at initiation of childbearing is
      associated with recurrence of perinatal mortality (PM), as well as its
      components: stillbirth and neonatal death. STUDY DESIGN: We conducted a
      population-based, retrospective cohort study on the Missouri maternally linked
      longitudinal data files comprising adolescent (10-19 years; n = 73,533) or mature
      (20-24 years; n = 78,618) mothers in their first pregnancy with follow-up in
      their second pregnancy to document the occurrence of PM or its components. The
      study covered the period 1989-2005. We used unconditional logistic regression
      modeling to generate odds ratios and to control for confounding. RESULTS: A
      history of perinatal mortality, stillbirth, or neonatal mortality increased the
      risk of a recurrence by 4-5 times. Among women with a history of PM or stillbirth
      in the first pregnancy, maternal age at initiation of pregnancy was not a risk
      factor for subsequent PM or its components. However, adolescent mothers with a
      history of neonatal mortality in the first pregnancy were about 5 times as likely
      to experience stillbirth in the second pregnancy, as compared to their mature
      counterparts. CONCLUSIONS: Young maternal age at the initiation of childbearing
      is not associated with an overall increased risk of recurrent perinatal loss.
      However, prior history of neonatal mortality among teen mothers is strongly
      predictive of subsequent stillbirth.

PMID- 20822848
TI  - Elephants can remember.

PMID- 20822849
TI  - Performance evaluation and application of molecularly imprinted polymer for
      separation of carbamazepine in aqueous solution.
AB  - A molecularly imprinted polymer (MIP) for selective adsorption of carbamazepine
      (CBZ) in aqueous solution was synthesized by precipitation polymerization using
      CBZ as a template molecule and methacrylic acid (MAA) as a functional monomer.
      The performance of the CBZ-MIP was evaluated in terms of selectivity, adsorption
      capacity, binding characteristics, loading volume, and elution volume. The CBZ
      MIP exhibited a high affinity for CBZ over the competitive compound (Diclofenac)
      and was more suitable to remove low concentrations of CBZ in large-volume water
      samples. A binding performance experiment indicated that the adsorption of CBZ
      MIP was characterized by both specific and non-specific binding interactions.
      Moreover, the regenerability of the MIP was affirmed in ten sequential cycles of
      adsorption/desorption without a significant loss in recovery. Finally, the CBZ
      MIP was applied to enrich CBZ in environmental water samples, and the CBZ
      concentrations were subsequently determined using HPLC-UV. The results were in
      good agreement with corresponding LC-MS/MS data.

PMID- 20822850
TI  - The interactions between spatial summation and DNIC: effect of the distance
      between two painful stimuli and attentional factors on pain perception.
AB  - The ability of a painful stimulus to suppress pain in another, remote area (DNIC)
      has been intensely studied. However, the effect of the distance between the two
      painful stimuli and the attentional factors during the measurement of pain
      perception received minimal treatment. We evaluated the effect of these factors
      on DNIC and on the interaction between DNIC and spatial summation (SS) of pain.
      Subjects rated the intensity of a test stimulus (applied to one hand) alone and
      simultaneously with conditioning stimuli applied to four different locations; 5
      and 30cm from the test stimulus on the same hand, the contralateral hand and
      contralateral leg. In each location, ratings were performed under three different
      instructions: summation, attention to test stimulus, attention to conditioning
      stimulus. The distance between the conditioning and test stimulus significantly
      affected pain perception (p<0.01) regardless of the instructions; SS occurred
      only at a distance of 5cm and DNIC occurred only in the remaining distances.
      DNIC's magnitude increased as the distance between the two stimuli increased
      (p<0.01). However, the instruction to summate attenuated DNIC and the DNIC
      instruction attenuated SS of pain. Attention to the conditioning stimulus induced
      a stronger DNIC than attention to the test stimulus (p<0.001). We conclude that
      (1) DNIC and SS of pain appear to be antagonistic processes. (2) DNIC is affected
      by the distance between two noxious stimuli and to a lesser extent, by attention.
      (3) The interaction between DNIC, SS and attention is complex and reflects the
      role of sensory-cognitive integration in pain perception.

PMID- 20822851
TI  - Asparaginase in the management of adult acute lymphoblastic leukaemia: is it used
      appropriately?
AB  - BACKGROUND: Whereas the disease free survival (DFS) continues to improve in
      paediatric acute lymphoblastic leukaemia (ALL), the prognosis of adult ALL has
      not altered significantly for last 2-3 decades. About 85% of children with ALL
      are leukaemia free at 5 years, but at best, only about 40% adults with 'standard
      risk' ALL remain in remission at that time. This is in spite of almost an equal
      proportion of adult patients achieving a complete remission as their much younger
      counterparts. Current data supports the efficacy of asparaginase in the treatment
      of ALL. PURPOSE: This review focuses on the role of asparaginase in the
      management of adult acute lymphoblastic leukaemia (ALL). It examines the current
      use of this agent in this disease and the potential for optimising its
      application and monitoring of efficacy in treatment regimens. CONCLUSION: Use of
      L-asparaginase has revolutionised the anti-leukaemia therapy in ALL. Early and
      sustained asparagine depletion, at least up to the first 30 weeks of therapy,
      appears to be crucial. Given the clear correlation between the depth of
      asparagine depletion and the patient outcome, asparaginase therapy should be
      monitored for adequate asparagine depletion for achievement of optimum results.

PMID- 20822852
TI  - How good is fine-grained Timeline Follow-back data? Comparing 30-day TLFB and
      repeated 7-day TLFB alcohol consumption reports on the person and daily level.
AB  - OBJECTIVE: This study examined the correspondence of two types of Timeline Follow
      back (TLFB) methods, a web-based self-administered, repeated 7-day TLFB and an
      interviewer-administered 30-day TLFB of alcohol consumption. METHOD: Participants
      were first- and second-year college students (n=323, 58.5% female). Day-to-day
      correspondence of drinking reports and correspondence of person-level indicators
      of drinking were assessed. RESULTS: Results indicated that correspondence between
      the TLFB-30 and TLFB-7 reports was generally good for summary indicators of
      drinking, but TLFB-7 data indicated a statistically significantly higher number
      of total drinks consumed, a higher number of days drinking 4+/5+ drinks per day,
      and a lower number of abstinent days than TLFB-30. Similarly, day-to-day
      comparison of drinking reports showed that drinking days were more frequently
      reported using the TLFB-7, a trend which was more pronounced for distal weekdays
      than recent weekdays. Correlations between TLFB-7 and TLFB-30 reports of drinks
      per drinking day were also lower for distal compared to recent weekdays (r=0.61
      vs. r=0.76). Using a Poisson regression model, a linearly increasing trend in the
      absolute value of the difference between TLFB-7 and TLFB-30 drinking reports per
      day as length of recall increases was found (b=0.013, z=4.43, with p<0.001).
      CONCLUSIONS: Our results indicate that participants reported more drinking on the
      repeated TLFB-7 than on the standard TLFB-30. Furthermore, the result of daily
      level analyses showed that discrepancies between the methods increased as the
      length of recall increased. These findings suggest that TLFB assessments covering
      longer intervals may have reduced accuracy on a fine-grained scale.

PMID- 20822853
TI  - Hyperactive immune cells (T cells) may be responsible for acute lung injury in
      influenza virus infections: a need for early immune-modulators for severe cases.
AB  - It has been believed that acute lung injury in influenza virus infections is
      caused by a virus-induced cytopathy; viruses that have multiplied in the upper
      respiratory tract spread to lung tissues along the lower respiratory tract.
      However, some experimental and clinical studies have suggested that the
      pathogenesis of acute lung injury in influenza virus infections is associated
      with excessive host response including a cell-mediated immune reaction. During
      the pandemic H1N1 2009 influenza A virus infections in Korea, we experienced a
      dramatic effect of immune-modulators (corticosteroids) on the patients with
      severe pneumonia who had significant respiratory distress at presentation and
      those who showed rapidly progressive pneumonia during oseltamivir treatment. We
      also found that the pneumonia patients treated with corticosteroids showed the
      lowest lymphocyte differential and that the severity of pneumonia was associated
      with the lymphocyte count at presentation. From our findings and previous
      experimental and clinical studies, we postulated that hyperactive immune cells (T
      cells) may be involved in the acute lung injury of influenza virus infections,
      using a hypothesis of 'protein homeostasis system'; the inducers of the cell
      mediated immune response are initially produced at the primary immune sites by
      the innate immune system. These substances reach the lung cells, the main target
      organ, via the systemic circulation, and possibly the cells of other organs,
      including myocytes or central nerve system cells, leading to extrapulmonary
      symptoms (e.g., myalgia and rhabdomyolysis, and encephalopathy). To control these
      substances that may be possibly toxic to host cells, the adaptive immune reaction
      may be operated by immune cells, mainly lymphocytes. Hyperimmune reaction of
      immune cells produces higher levels of cytokines which may be associated with
      acute lung injury, and may be controlled by early use of immune-modulators. Early
      initiation and proper dosage of immune-modulators with antiviral agents for
      severe pneumonia patients may reduce morbidity and prevent progressive fatal
      pneumonia.

PMID- 20822854
TI  - Reasonable neuropsychological battery to identify mild cognitive impairment.
AB  - Mild cognitive impairment (MCI) was popular studied while the neuropsychological
      tests to evaluate and identify MCI patients were not standard used. So there is a
      need to develop objective, cost-effective and normative screening tests which can
      evaluate cognitive problems for older individuals at risk of Alzheimer's disease
      (AD). According to lots of valuable research results, we hypothesize that a
      neuropsychological battery containing MMSE, AVLT, and MoCA could successfully
      identify MCI from other cognitive impairment. And CDT in MoCA should not only be
      scored by a 3-point scoring method but for the second time in qualitative
      assessments and quantitative analysis independently. This battery measures almost
      the broadest aspects of cognition in relatively short time to avoid lacking of
      concentration due to long time. Of course, general physical examinations and a
      computed tomography (CT) or magnetic resonance imaging (MRI) brain scan should be
      performed before neuropsychological tests to exclude neurologic diseases which
      would affect cognition.

PMID- 20822855
TI  - Possible contribution of intraocular tumour-associated lymphangiogenesis to the
      novel uveolymphatic pathway.

PMID- 20822856
TI  - Chronic intermittent hypoxia caused by obstructive sleep apnea may play an
      important role in explaining the morbidity-mortality paradox of obesity.
AB  - Obesity has reached global pandemic that threatens the health of millions of
      people and is associated with numerous morbidities such as hypertension, type II
      diabetes mellitus, dyslipidemia, cor pulmonale, gallbladder disease, obstructive
      sleep apnea (OSA), certain cancers, osteoarthritis, increased surgical risk and
      postoperative complications, lower extremity venous and/or lymphatic problems,
      pulmonary embolism, stroke/cerebrovascular diseases and coronary arterial
      disease. Despite all these adverse associations, numerous studies and meta
      analyses have documented an "obesity paradox" in which overweight and obese
      population with established cardiovascular disease have a better prognosis than
      do their lean counterparts. There are potential and plausible explanations
      offered by literature for these puzzling data; however, it still remains
      uncertain whether this phenomenon is attributable to a real protective effect of
      high body fat mass. In recent years, the survival advantage of patients with OSA,
      combined with the potential cardioprotective effects of chronic intermittent
      hypoxia, raise the possibility that apneas during sleep may activate
      preconditioning-like cardioprotective effect. Chronic intermittent hypoxia, one
      of the physiological markers of OSA, is characterized by transient periods of
      oxygen desaturation followed by reoxygenation, and is a major cause of its
      systemic harmful (oxidative stress, inflammation, sympathetic activity,
      vasculature remodelling and endothelial dysfunction) and/or protective
      (preconditioning-like cardioprotective) effects. Since many OSA subjects are
      obese, and obesity is an independent risk factor for many comorbidities
      associated with OSA; and also most OSA has never been diagnosed in obese
      patients, we hypothesed that the chronic intermittent hypoxia caused by OSA in
      obese patients may be one of the underlying mechanisms in morbi-mortality paradox
      of obesity.

PMID- 20822857
TI  - Rotational stress: role in development of ossification of posterior longitudinal
      ligament and ligamentum flavum.
AB  - Ossification of the posterior longitudinal ligament (OPLL) and ossification of
      ligamentum flavum (OLF) are characterized by progressive ectopic bone formation
      in the spinal ligaments. OPLL and OLF involved multiple etiological factors, and
      mechanical stress plays an important role. However, the details that what kind of
      mechanical stress promotes ligament ossification are still unknown. In this
      paper, we try to make a hypothesis that rotational mechanical stress might play a
      key role in OPLL and OLF development. It was supported by the conclusions that
      drawn from literature review: (1) Lumbar spine had the lowest prevalence of OPLL
      and OLF. (2) Lumbar spine was most rigid in axial rotation. (3) Atlanto-axial
      fusion might cause the development of sub-axial cervical OPLL. (4) Incidence of
      OLF was related to the range of rotation of the vertebrae.

PMID- 20822858
TI  - High-BMI: a possible risk factor for sport-related sudden death?

PMID- 20822859
TI  - A possible mechanism of sadism.
AB  - Sadists enjoy inflicting pain upon others. The pathophysiology of sadism is
      poorly understood but the traits of major psychiatric disorders have been noted
      among these people. Because an abnormal threshold for pain occurs in major
      psychiatric disorders, I here hypothesize that the practice of sadism may be used
      as self-medication for an inherently aberrant pain pathway. The neurobiological
      basis of the mechanism and its possible relevance in the treatment of psychiatric
      disorders await further study.

PMID- 20822860
TI  - 7-Ketocholesterol and 7-hydroxycholesterol in pork meat and its gravy thermally
      treated without additives and in the presence of onion and garlic.
AB  - The effect of onion and garlic on the formation of two cholesterol oxidation
      products (COPs): 7-ketocholesterol and 7-hydroxycholesterol was evaluated by
      comparing their concentrations in meat and gravy samples obtained from three pork
      dishes prepared in the presence and absence of these flavourings. The
      concentration of these compounds in meat samples was between 82.4 and 1331.6 ng/g
      of cooked meat. Gravies contained lower amounts: from 18.3 to 45.6 ng/g of cooked
      meat. The addition of onion (30 g/100g of meat) caused a decrease in 7
      ketocholesterol and 7-hydroxycholesterol concentrations in all of the
      investigated pork dishes by 9.5-79%, whilst the addition of 15 g of garlic to
      100g of meat lowered the concentration by 17 to 88%. The greatest decrease was
      found in grilled minced chops. The quantitative assessment of 7-ketocholesterol
      and 7-hydroxycholesterol was carried out by thin-layer chromatography with
      densitometric detection.

PMID- 20822861
TI  - [Activated partial thromboplastin time prolongation in paediatrics. Retrospective
      monocentric study at the Nice University Hospital].
AB  - The study of hemostasis often arises in paediatrics. Evidence of activated
      partial thromboplastin time (aPTT) prolongation sometime due to the presence of a
      circulating anticoagulant (antiphospholipid syndrome [APS]) may be embarrassing
      for the physician. AIM OF THE STUDY: To evaluate the prevalence of this
      situation, to identify the leading indicators and assess their impact. PATIENTS
      AND METHOD: All children aged 1 to 18 years old undergoing blood sample whatever
      was the reason, at the Nice University Hospital with existing isolated aPTT
      prolongation, were included. The assessment was completed by a mixing test,
      calculation of Rosner's index as well as the study of an APS and the measurement
      of factor VIII, IX, XI, XII. RESULTS: Between July 2006 and March 2008, 27 of
      1845 children observed (1.5%) were selected for further study. Mean age was 6.17
      years old. For 16 of the patients, aPTT prolongation was fortuitously discovered.
      Symptomatic subjects were older (9.8 vs. 5.2 years of age; P = 0.03). A
      significantly higher aPTT was indicative of an APS and predicted a positive
      Rosner Test outcome. A prolongated kaolin clotting time, observed among the
      younger subjects (3.45 vs. 8.88 years of age; P = 0.0011), was associated with a
      high aPTT prolongation (57.3 vs. 42.6s; P = 0.0009). CONCLUSION: In our study,
      the discovery of a prolongated aPTT is most often incidental and tends to occur
      during winter. The presence of a highly prolongated aPTT, abnormal kaolin
      clotting time and positive Rosner Test are strong predictors of the existence of
      an APS, especially in very young children. These antibodies are nonpathogenic and
      transitional.

PMID- 20822862
TI  - [Usefulness of PCR test for the management of a Mycoplasma pneumoniae outbreak in
      Bethune Hospital (Pas-de-Calais, France)].
AB  - SUBJECT: Molecular amplification (PCR) provides adequate rapid and specific
      diagnosis of Mycoplasma pneumoniae infection (first agent responsible for
      community-wide bacterial pneumonia in children above 5 years of age). METHOD:
      Positive (Chlamylege((r)), Argene) PCR in nasopharyngeal aspirate, respiratory
      samples and nasopharyngeal swab and/or positive serological test (ELISA).
      RESULTS: Diagnosis of M. pneumoniae infection in 39 cases: 31 between September
      and December 2008 (30 children and one adult) and eight since June 2009 (three
      adults and five children). Children (mean age: 3.6years) were hospitalized in
      88.6% of cases, mean hospitalization duration was 2.9 days for respiratory tract
      infections, mainly due to lack of response to beta-lactamines therapy (65.7%).
      Four adults (mean age: 29.5 years) presented a pneumonia, with hospitalization
      for three of them with one in intensive care unit. Twenty-eight PCR have proved
      positive (87%): without associated serology (13), eight negative serologies, IgG
      and IgM positive (five), and IgG alone (two). Seven patients had only serological
      test for diagnosis: IgM+/-IgG. For two children, IgM positive only in isolation,
      with a PCR probably false negative. CONCLUSION: The sensitivity of the serology
      in the diagnosis of mycoplasma infection is limited: IgM, which appear
      traditionally 1 week after clinical signs are mostly inexistent for adults and
      IgG rise at a later stage. Early diagnosis of child pneumoniae by PCR helped
      rapidly characterize this epidemic phenomenon and adapt the treatment.

PMID- 20822863
TI  - [A priori prediction of gentamicin peak concentrations: Use of a simple and
      practical tool].
AB  - Aminoglycosides are concentration-dependent killing antibiotics, so that it is
      necessary to obtain elevated peak levels to reach the pharmacokinetic
      pharmacodynamic objectives. Because of their nephrotoxicity, this class of
      antibiotics are frequently underprescribed and giving at an insufficient dosage
      when prescribed. That is why therapeutical drug monitoring (TDM) of
      aminoglycosides is recommanded to assess efficacy. Unfortunately, this TDM allows
      not a dosage adaptation on the first dose of aminoglycosides. The aim of the work
      was to elaborate a model using simple pharmacokinetics formulae to estimate
      gentamicin peak levels and so to propose an optimal a priori dosage on the first
      dose of gentamicin. The final model was tested out on 24 patients treated by
      gentamicin. The model was able to predict gentamicin peak levels in 62% of
      patients with a 10% precision and in 79% of patients with a 15% precision. Using
      this simple and practical tool might avoid under-dosage of gentamicin and
      clinical failure due to the selection of resistant bacteriae.

PMID- 20822864
TI  - [Genetic diversity of a rare hepatitis A virus genotype].
AB  - PURPOSE OF THE STUDY: Very few is known on genotype II hepatitis A virus (HAV)
      since it is rarely isolated. From 2002 to 2007, the French observatory of HAV
      identified six sub-genotype IIA strains of which one from a patient having
      travelled to West Africa. To investigate the possible African origin of sub
      genotype IIA, we determined its prevalence among French travellers in 2008 and
      characterised its genetic variability. PATIENTS AND METHODS: The 2008 mandatory
      notification records were screened for travel to Africa. Viral genotype was
      determined on the nucleotide sequencing of the VP1/2A junction region. The P1
      region coding for capsid proteins was used to compare the genetic diversity of
      IIA isolates to those of other genotypes. RESULTS: In 2008, five out of 54
      patients returning from West Africa were infected by IIA strains and an
      additional "autochthonous" case was identified. Two more African cases were
      identified in 2009. A total of 14 IIA isolates (eight African and six
      "autochthonous") were analysed. Nucleotide and amino-acid variability of IIA
      sequences was lower than that of the other genotypes. Phylogenetic analysis
      revealed the clustering of two "autochthonous" cases with African isolates
      whereas the other ones belonged to a different lineage. CONCLUSION: Most IIA
      strains isolated in France are imported by travellers returning from West Africa.
      However, the unexplained contamination mode of some "autochthonous" cases
      suggests another geographical origin to discover or a French reservoir to
      explore.

PMID- 20822865
TI  - [Development and validation of a specific method for relative HBV-genotype G (G
      HBV) quantification in the context of co-infection with other genotypes].
AB  - GOAL OF THE STUDY: A detection and quantification method specific of genotype G
      hepatitis B virus (G-HBV) was developed and used to study the epidemiology and
      evolution of G-HBV co-infection during antiviral therapy. PATIENTS AND METHODS: A
      multiplex real time PCR was developed and validated on A-HBV and G-HBV plasmid
      mixes. G-HBV infection was sought for on chronic hepatitis B carriers followed in
      our institution. RESULTS: Two primers, flanking the specific G-HBV 36 nucleotide
      insertion and two probes, including one specific for the insertion, were
      validated for a multiplex real time PCR. This new tool was well correlated to
      commercially available quantification systems within a 2 to 7 log(10) IU/mL
      range. On A- and G-HBV clonal mixes, G-HBV was quantified with a precision
      between 5 to 10%. On HBV-HIV infected patients, a 25% G-HBV prevalence was found,
      while it was below 1% in HBV mono-infected patients. Longitudinal G-HBV
      quantifications on five treated patients indicate that G-HBV is not selected by
      antiviral treatment. CONCLUSION: A specific method for G-HBV quantification
      within multi-genotype mixes was set up. The important G-HBV prevalence in HIV
      patients was unexpected. Our data are not in favour of an intrinsic resistance of
      G-HBV to current antivirals.

PMID- 20822866
TI  - [Monitoring of chimerism in myeloid cells sorting of transplanted patients with
      acute myeloid leukaemia: a study from Lyon (France)].
AB  - Chimerism analysis after allogeneic haematopoietic stem cell transplantation has
      been used to document engraftment and to adapt therapy promptly. The aim of this
      study was to document engraftment and to detect as soon as possible relapse in
      patients with acute myeloid leukaemia who underwent stem cell transplantation.
      Real-time quantitative polymerase chain reaction is a highly sensitive and
      reproducible technology. It is useful in some disease to target selected sub
      populations in order to have an earlier detection of relapse on cell fractions.
      In the acute myeloid leukaemia (n=65), analysis of the chimerism on whole
      peripheral blood cells and bone marrow cells, CD3+ cells, specific myeloid CD33+
      cells (from blood) and CD34+ cells (from bone marrow) is of importance. After
      transplant, 25 patients relapsed (38%), three massively, with chimerism detection
      in whole blood and bone marrow and 22 insidiously following two different schemes
      (GRI and GRII). In GRI, (n=13): chimerism of CD33+ and CD34+ cellular fractions
      allowed an early detection of relapse in 100% of cases undetected in whole cells
      whereas in GRII (n=9): myeloid cells could identified relapse in 89% of cases
      when whole blood cells and CD3+ cells expressed a mixed chimerism. This study
      highlighted the importance of sub-cellular population chimerism documentation
      enable to ascertain a stable engraftment and to detect early relapse. The
      selection of sub-cellular population studied with high sensitive technology
      allows a rapid and efficient intervention before the onset of clinical signs in
      patient with acute myeloid leukaemia and could improve the patient's follow-up.

PMID- 20822867
TI  - Sequential combination of self-report, breath carbon monoxide, and saliva
      cotinine to assess smoking status.
AB  - The purpose of this analysis was to develop an algorithm for the cost effective
      and accurate assessment of smoking during the previous few days by combining self
      report, breath carbon monoxide (BCO), and saliva cotinine (sCOT). These
      measurements are convenient, quantitative, and do not require invasive
      procedures. The data used to devise the algorithm were gathered during a
      treatment trial of participants seeking to stop smoking. Self-report of smoking
      was determined using a written questionnaire, BCO was measured with a handheld
      breathalyzer, and sCOT was quantified using a high sensitivity ELISA.
      Participants were 130 males and 97 females between the ages of 19 and 67 years
      who reported smoking at least 15 cigarettes a day and had a BCO level >= 15 ppm.
      Self-reports and BCO levels were collected at each of 6 visits (V0-V5) and sCOT
      levels were determined at V0 and V5. Based on the data collected, we recommend
      that the sequential determination of self-reported smoking, BCO level, and sCOT
      level be employed to assess smoking during the previous few days to minimize the
      higher cost and longer turnaround time associated with the sCOT test while
      maximizing accuracy.

PMID- 20822868
TI  - The relativity of integrity testing by telemetry in the diagnosis of cochlear
      implant defect: A case study and literature review.
AB  - OBJECTIVE: This paper report a rare case that showed the limitation of integrity
      testing by telemetry in detecting the cause of cochlear implant defect. METHOD:
      We are reporting the case of a 45-year-old female who received a cochlear implant
      10 years ago, owing to a profound bilateral sensorineural hearing loss. Following
      the cochlear implant the patient's speech discrimination threshold improved
      dramatically. In March 2009, after a car accident, the patient was unable to
      hear. The clinical and radiological examination revealed no abnormality, nor did
      the telemetry test, with normal implant function and normal NRT. The proceeding
      medical treatment with a corticosteroid therapy and hearing rehabilitation
      brought no improvement. Thus we decided to revise both implantations. RESULT: The
      cochlear reimplantation was postoperatively found to have brought a marked
      improvement in the hearing and speech discrimination threshold. Conclusively we
      chose to perform a second cochlear reimplantation on the opposite side which
      after surgery revealed the same postoperative result. CONCLUSION: The telemetry
      test does not always enable one to discover the cause of the cochlear implant
      failure.

PMID- 20822869
TI  - Leptin as a new approach for treatment for autism and epilepsy, a hypothesis with
      clinical implications.

PMID- 20822870
TI  - [Inadequate vaccination coverage in a French cohort of HIV positive patients].
AB  - INTRODUCTION: HIV patients have a high rate of infectious complications.
      Vaccination, though less efficient in case of severe immunosuppression, can
      prevent some of these infections. Since 2006, new vaccine recommendations have
      been elaborated in France. We studied the vaccine status of HIV+ patients for
      influenza, Streptococcus pneumoniae, tetanus, and hepatitis A and B among an
      alsatian HIV+ population. PATIENTS AND METHODS: From August 20, 2007 to September
      15, 2007, HIV patients of the Alsace HIV center (COREVIH) were included in a
      prospective study, screening demographic, medical, immunovirological, and
      vaccination data. RESULTS: Three hundred and thirty-one patients were included,
      49% of whom were asymptomatic, 29% symptomatic without AIDS, 18% at AIDS stage,
      and no documentation for 4%. Seventy-one patients (21.4%) were vaccinated against
      influenza, 11 (3.3%) against Streptococcus pneumoniae, 34 against HAV (only 16.3%
      of patients with a negative test before), 120 against HBV (60% of patients with
      no serological markers before), and 186 (56.2%) against tetanus. The most
      frequent reasons for non-vaccination were non-proposal by physicians, lack of
      expected effectiveness, and fear of an immunovirological adverse effect.
      CONCLUSION: Vaccination coverage for recommended vaccines of HIV infected people
      remains at a low level and appears sometimes inferior to the rates reached among
      the general French population. It is necessary to inform prescribers and HIV
      positive patients about the interest of vaccination.

PMID- 20822871
TI  - Celiac crisis in a patient with chronic lymphocytic  leukemia and
      hypogammaglobulinemia.
AB  - Celiac crisis is an acute, fulminant form of celiac disease manifesting with
      severe diarrhea, metabolic and electrolyte abnormalities, and weight loss. It is
      mostly seen in children, and there are very few reports in adults. We present a
      67-year-old patient with chronic lymphocytic leukemia (CLL) who presented with
      weight loss of 40 pounds, severe diarrhea, hypoalbuminemia and hypokalemia. The
      patient was immunosuppressed with hypogammaglobulinemia, which is common in CLL.
      Thus, the patient had negative serological studies for celiac disease. An
      endoscopic evaluation and HLA typing supported the diagnosis of celiac disease.
      Although the differential diagnosis was broad, exclusion of other etiologies for
      diarrhea, prompt diagnosis of celiac disease and initiation of gluten-free diet
      resolved the crisis. This is the first such report of a patient presenting with
      celiac crisis on a background of hypogammaglobulinemia.

PMID- 20822872
TI  - Outcome of patients with obscure gastrointestinal bleeding after negative capsule
      endoscopy: results of a one-year follow-up study.
AB  - BACKGROUND: Capsule endoscopy (CE) is an effective method for investigating the
      small bowel, especially in cases of obscure gastrointestinal bleeding (OGIB),
      although the long-term outcome of patients with a negative CE is generally not
      known. PATIENTS AND METHODS: For 49 patients with OGIB and a negative CE, their
      referring physicians filled out a follow-up questionnaire to assess bleeding
      recurrence and any repeat investigations after negative video capsule endoscopy
      (VCE). RESULTS: A minimum follow-up duration of one year (median: 15.9 months)
      was available for 35 patients with an overall rebleeding rate of 23% (n=8). Of
      these eight patients, four women presented with recurrence prior to new
      investigations. In the four remaining patients, repeat endoscopy work-ups after
      negative CE were performed and revealed previously missed lesions with bleeding
      potential, mainly in the stomach. Overall, 13 patients, with or without
      rebleeding, had repeat endoscopy work-ups after a negative CE, leading to a
      definitive diagnosis in nine patients, with lesions located in the stomach and
      colon in eight of them. CONCLUSION: Patients with OGIB and a negative CE had a
      low rate of rebleeding. This study highlights the importance of the initial
      endoscopy work-up, and suggests that CE be proposed after a minimum of two
      gastroscopies and one complete colonoscopy.

PMID- 20822873
TI  - Treatment of fistula-in-ano with the Surgisis((r)) AFP(TM) anal fistula plug.
AB  - OBJECTIVE: Closure of the fistula tract with an anal fistula plug has been
      reported to provide success rates as high as 80%. The purpose of this study was
      to evaluate our results with this new method. METHOD: From June 2006 to September
      2007, an anal fistula plug was used for the treatment of high transsphincteric
      fistulas. Success was defined as no residual leakage or abscess formation and
      closure of the external opening. RESULTS: Fifteen patients (seven women), median
      age 46 years (range 32-58 years), were included in the study. Three had Crohn's
      disease, three had an anovulvar fistula and seven had undergone previous surgical
      repair attempts. Three patients expelled the prosthesis on postoperative day 2, 5
      and 7, respectively, and a second plug placement was followed by expulsion again.
      One patient developed an abscess that was noted on postoperative day 4. The
      fistula tract healed in 6/15 patients (40%) after 3 months and in 8/15 (53.3%)
      after 7 months. The success rate in Crohn's disease was 33%. No significant
      difference was found between patients with or without previous surgical repair.
      CONCLUSION: In our experience, this simple technique provided success rates of
      40% at 3 months and 53% at 7 months.

PMID- 20822874
TI  - Phaseolus vulgaris seed-borne endophytic community with novel bacterial species
      such as Rhizobium endophyticum sp. nov.
AB  - The bacterial endophytic community present in different Phaseolus vulgaris (bean)
      cultivars was analyzed by 16S ribosomal RNA gene sequences of cultured isolates
      derived from surface disinfected roots and immature seeds. Isolated endophytes
      from tissue-macerates belonged to over 50 species in 24 different genera and some
      isolates from Acinetobacter, Bacillus, Enterococcus, Nocardioides, Paracoccus,
      Phyllobacterium, and Sphingomonas seem to correspond to new lineages. Phytate
      solubilizing bacteria were identified among Acinetobacter, Bacillus and
      Streptomyces bean isolates, phytate is the most abundant reserve of phosphorus in
      bean and in other seeds. Endophytic rhizobia were not capable of forming nodules.
      A novel rhizobial species Rhizobium endophyticum was recognized on the basis of
      DNA-DNA hybridization, sequence of 16S rRNA, recA, rpoB, atpD, dnaK genes,
      plasmid profiles, and phenotypic characteristics. R. endophyticum is capable of
      solubilizing phytate, the type strain is CCGE2052 (ATCC BAA-2116; HAMBI 3153)
      that became fully symbiotic by acquiring the R. tropici CFN299 symbiotic plasmid.

PMID- 20822875
TI  - Heterologous expression of glycoside hydrolase family 2 and 42 beta
      galactosidases of lactic acid bacteria in Lactococcus lactis.
AB  - This study characterized a glycoside hydrolase family 42 (GH42) beta
      galactosidase of Lactobacillus acidophilus (LacA) and compared lactose
      hydrolysis, hydrolysis of oNPG, pNPG and pNPG-analogues and
      galactooligosaccharides (GOSs) formation to GH2 beta-galactosidases of
      Streptococcus thermophilus (LacZ type), Lactobacillus plantarum and Leuconostoc
      mesenteroides subsp. cremoris (both LacLM type). Beta-galactosidases were
      heterologously expressed in Lactococcus lactis using a p170 derived promoter;
      experiments were performed with L. lactis crude cell extract (CCE). The novel
      GH42 beta-galactosidase of Lb. acidophilus had lower activity on lactose, oNPG
      and pNPG but higher relative activity on pNP analogues compared to GH2 beta
      galactosidases, and did not transgalactosylate at high lactose concentrations.
      Temperature and pH optima for lactose hydrolysis varied between GH2 beta
      galactosidases. oNPG and pNPG were the preferred substrates for hydrolysis; in
      comparison, activity on pNPG-analogues was less than 1.5%. GH2 beta
      galactosidases formed structurally similar GOS with varying preferences. The
      diversity of lactic acid bacteria beta-galactosidase activity in L. lactis CCE
      can be exploited in future nutritional or therapeutic applications.

PMID- 20822876
TI  - Acute low back pain in an elderly woman.

PMID- 20822877
TI  - Maximizing your Patient Education Skills (MPES): a multi-site evaluation of an
      innovative patient education skills training course for oncology health care
      professionals.
AB  - OBJECTIVE: To evaluate the acceptability and relevance of the Maximizing your
      Patient Education Skills (MPES) course and to determine whether it significantly
      improved knowledge regarding patient education (PE) theory, self-assessed PE
      competencies, and PE skills using case based vignettes. METHODS: 1-Group, multi
      site, pre-post-intervention. Participants completed a pre-assessment (T1),
      participated in the 4-h MPES course, and then a 3-month post-assessment (T2). A
      focus group was conducted with sub-set of participants. RESULTS: 98 (75%) of
      participants completed both time points. Participants were highly satisfied with
      MPES and found it to be relevant. Results showed that MPES had a significant
      impact on all of our outcome measures. CONCLUSION: Findings from this study show
      that oncology HCPs knowledge of patient education theory, self-assessed
      competencies and skills can improve after participating in a brief problem
      focused and interactive workshop. PRACTICE IMPLICATIONS: Given the evidence that
      well-planned education and support can contribute to a number of positive health
      outcomes and the evidence that HCPs may lack the skills to teach and support
      patients and their families effectively, these results suggest that MPES course
      may be of value to oncology professionals. Efforts to further develop this course
      include exploring alternative funding models and using different learning
      platforms.

PMID- 20822878
TI  - Validation of the Alcohol Use Disorders Identification Test and the Drug Use
      Disorders Identification Test in a Swedish sample of suspected offenders with
      signs of mental health problems: results from the Mental Disorder, Substance
      Abuse and Crime study.
AB  - Substance abuse is common among offenders. One method widely used for the
      detection of substance abuse is screening. This study explored the concurrent
      validity of the Alcohol Use Disorders Identification Test (AUDIT) and the Drug
      Use Disorders Identification Test (DUDIT) screening tools in relation to (a)
      substance abuse and dependency diagnoses and (b) three problem severity domains
      of the sixth version of the Addiction Severity Index in a sample of 181 suspected
      offenders with signs of mental health problems. The screening tools showed
      moderate to high accuracy for identification of dependency diagnoses. The AUDIT
      was associated with alcohol problem severity, whereas the DUDIT was associated
      with drug and legal problem severity. Administering the screening tools in the
      current population yields valid results. However, the suggested cutoff scores
      should be applied with caution due to the discrepancy between present and
      previous findings.

PMID- 20822879
TI  - Motivation for reducing substance use among minority adolescents: targets for
      intervention.
AB  - Motivation to change substance use is considered to be one of the most important
      predictors of client readiness for alcohol and other drug treatment and ability
      to benefit from treatment. Enhancing motivation to change substance use is an
      important emphasis of many substance use intervention programs. The specific
      factors predicting motivation to change substance use remain largely unidentified
      and poorly understood, particularly among racial/ethnic minority youth. This
      study examines the influence of adolescent and parental factors on motivation to
      change substance use among 310 alcohol-using and/or drug-using racial/ethnic
      minority adolescent males. The analytic plan involved the use of structural
      equation modeling. Adolescents' motivation to change substance use was influenced
      directly and indirectly by parental factors, as well as by adolescent substance
      use severity and externalizing disorders. Findings have implications for
      treatment with racial/ethnic minority youth, as parental factors may be
      exceptionally useful targets for interventions aimed at enhancing motivation to
      reduce substance use among these at-risk youth.

PMID- 20822880
TI  - [Proton pump inhibitors and clopidogrel: what are we doing now?].

PMID- 20822881
TI  - Assessing the factor structure of posttraumatic stress disorder symptoms in war
      exposed youths with and without Criterion A2 endorsement.
AB  - Posttraumatic stress disorder's (PTSD) tripartite factor structure proposed by
      the DSM-IV is rarely empirically supported. Other four-factor models (King et
      al., 1998; Simms et al., 2002) have proven to better account for PTSD's latent
      structure; however, results regarding model superiority are conflicting. The
      current study assessed whether endorsement of PTSD's Criterion A2 would impact on
      the factorial invariance of the King et al. (1998) model. Participants were 1572
      war-exposed Bosnian secondary students who were assessed two years following the
      1992-1995 Bosnian conflict. The sample was grouped by those endorsing both parts
      of the DSM-IV Criterion A (A2 Group) and those endorsing only A1 (Non-A2 Group).
      The factorial invariance of the King et al. (1998) model was not supported
      between the A2 vs. Non-A2 Groups; rather, the groups significantly differed on
      all model parameters. The impact of removing A2 on the factor structure of King
      et al. (1998) PTSD model is discussed in light of the proposed removal of
      Criterion A2 for the DSM-V.

PMID- 20822882
TI  - Cerebral Visual Impairment: which perceptive visual dysfunctions can be expected
      in children with brain damage? A systematic review.
AB  - The current definition of Cerebral Visual Impairment (CVI) includes all visual
      dysfunctions caused by damage to, or malfunctioning of, the retrochiasmatic
      visual pathways in the absence of damage to the anterior visual pathways or any
      major ocular disease. CVI is diagnosed by exclusion and the existence of many
      different causes and symptoms make it an overall non-categorized group. To date,
      no discrimination is made within CVI based on types of perceptive visual
      dysfunctions. The aim of this review was to outline which perceptive visual
      dysfunctions are to be expected based on a number of etiologies of brain damage
      and brain development disorders with their onset in the pre-, peri- or postnatal
      period. For each period two etiologies were chosen as the main characteristic
      brain damage. For each etiology a main search was performed. The selection of the
      articles was based on the following criteria: age, etiology, imaging, central
      pathology and perceptive visual function test. The perceptive visual functions
      included for this review were object recognition, face recognition, visual
      memory, orientation, visual spatial perception, motion perception and
      simultaneous perception. Our search resulted in 11 key articles. A diversity of
      research history is performed for the selected etiologies and their relation to
      perceptive visual dysfunctions. Periventricular Leukomalacia (PVL) was most
      studied, whereas the main tested perceptive visual function was visual spatial
      perception. As a conclusion, the present status of research in the field of CVI
      does not allow to correlate between etiology, location and perceptive visual
      dysfunctions in children with brain damage or a brain development disorder. A
      limiting factor could be the small number of objective tests performed in
      children experiencing problems in visual processing. Based on recent insights in
      central visual information processing, we recommend an alternative approach for
      the definition of CVI that is based on functional visual processing, rather than
      anatomical landmarks. This could be of benefit in daily practice to diagnose CVI.

PMID- 20822883
TI  - Disrupted Mer receptor tyrosine kinase expression leads to enhanced MZ B-cell
      responses.
AB  - Control of lymphocyte homeostasis is essential to ensure efficient immune
      responses and to prevent autoimmunity. Splenic marginal zone B cells are
      important producers of autoantibodies, and are subject to stringent tolerance
      mechanisms to prevent autoimmunity. In this paper, we explore the role of the Mer
      tyrosine kinase (Mertk) in regulating autoreactive B cells. This receptor
      tyrosine kinase serves to bind apoptotic cells, to mediate their phagocytosis,
      and to regulate subsequent cytokine production. Mice lacking Mertk suffer from
      impaired apoptotic cell clearance and develop a lupus-like autoimmune syndrome.
      Here we show that such Mertk-KO mice have expanded numbers of splenic marginal
      zone B cells. Mertk-KO mice bearing a DNA-specific immunoglobulin heavy-chain
      transgene (3H9) produced anti-DNA antibodies that appeared to be secreted largely
      by marginal zone B cells. Finally, Mertk-KO mice developed greater antibody
      responses after NP-Ficoll immunization than their B6 counterparts. Taken
      together, our data show that Mertk has a major effect on the development of the
      marginal zone B-cell compartment. Mertk is also important in establishing DNA
      specific B-cell tolerance in 3H9 anti-DNA transgenic mice.

PMID- 20822885
TI  - Circulating level of chemerin is upregulated in psoriasis.

PMID- 20822884
TI  - Gray matter volume reduction in rostral middle frontal gyrus in patients with
      chronic schizophrenia.
AB  - The dorsolateral prefrontal cortex (DLPFC) is a brain region that has figured
      prominently in studies of schizophrenia and working memory, yet the exact
      neuroanatomical localization of this brain region remains to be defined. DLPFC
      primarily involves the superior frontal gyrus and middle frontal gyrus (MFG). The
      latter, however is not a single neuroanatomical entity but instead is comprised
      of rostral (anterior, middle, and posterior) and caudal regions. In this study we
      used structural MRI to develop a method for parcellating MFG into its component
      parts. We focused on this region of DLPFC because it includes BA46, a region
      involved in working memory. We evaluated volume differences in MFG in 20 patients
      with chronic schizophrenia and 20 healthy controls. Mid-rostral MFG (MR-MFG) was
      delineated within the rostral MFG using anterior and posterior neuroanatomical
      landmarks derived from cytoarchitectonic definitions of BA46. Gray matter volumes
      of MR-MFG were then compared between groups, and a significant reduction in gray
      matter volume was observed (p<0.008), but not in other areas of MFG (i.e.,
      anterior or posterior rostral MFG, or caudal regions of MFG). Our results
      demonstrate that volumetric alterations in MFG gray matter are localized
      exclusively to MR-MFG. 3D reconstructions of the cortical surface made it
      possible to follow MFG into its anterior part, where other approaches have
      failed. This method of parcellation offers a more precise way of measuring MR-MFG
      that will likely be important in further documentation of DLPFC anomalies in
      schizophrenia.

PMID- 20822886
TI  - Antimicrobial susceptibility and resistance determinants of Clostridium butyricum
      isolates from preterm infants.
AB  - This study reports the antibiotic susceptibility and genetic resistance
      determinants of 39 Clostridium butyricum strains isolated from the faeces of
      preterm infants as well as one reference strain. Results showed that all the
      strains were susceptible to cefoxitin, imipenem, vancomycin, tigecycline,
      metronidazole, chloramphenicol and linezolid. Resistance was observed to
      clindamycin (100%), penicillin G, amoxicillin and piperacillin (15%),
      tetracycline (7.5%) and erythromycin (5%). Investigation of the genetic basis of
      the observed resistance phenotypes showed that resistance to penicillin was due
      to beta-lactamase activity and that resistance to tetracycline involved tet(O) or
      tet(O/32/O) homologue genes. Clindamycin and erythromycin resistance may involve
      another genetic determinant, different from those commonly described for
      clostridia.

PMID- 20822887
TI  - Protective effect of quercitrin against hydrogen peroxide-induced dysfunction in
      osteoblastic MC3T3-E1 cells.
AB  - The protective effect of quercitrin on the response of osteoblastic MC3T3-E1
      cells to oxidative stress was evaluated. Osteoblasts were incubated with H(2)O(2)
      and/or quercitrin, and markers of osteoblast function and oxidative damage were
      examined. Quercitrin treatment reversed the cytotoxic effect of H(2)O(2)
      significantly (P<0.05). This effect was blocked by ICI182780 and LY294002,
      suggesting that quercitrin's effect might be involved in estrogen action and
      results from PI3K mediated signaling pathway. Pretreatment of quercitrin
      increased collagen content, alkaline phosphatase (ALP) activity, and calcium
      deposition of osteoblasts compared with H(2)O(2) treated cells and these effects
      were blocked by ERKs and p38 mitogen-activated protein kinases (MAPKs) inhibitors
      such as PD98059 and SB203580, respectively. These suggest that quercitrin-induced
      protective effect against osteoblast dysfunction by oxidative stress is
      associated with increased activation of ERKs and p38 MAPK. Pretreatment with
      quercitrin also reduced the increase in bone-resorbing factor, receptor activator
      of nuclear factor-kB ligand (RANKL) and oxidative damage markers
      (malondialdehyde, protein carbonyl, and nitrotyrosine) induced by H(2)O(2). These
      results suggest that quercitrin may be protective against H(2)O(2)-induced
      dysfunction in osteoblasts.

PMID- 20822888
TI  - The 'chemoinvasion' assay, 25 years and still going strong: the use of
      reconstituted basement membranes to study cell invasion and angiogenesis.
AB  - Invasive and metastatic cells must cross basement membranes (BMs) in order to
      disseminate to distant sites. The 'chemoinvasion assay' using a reconstituted
      basement membrane, matrigel, in Boyden blind-well chambers was developed 25 years
      ago as a tool for invasion and metastasis research. Since then, it was adapted
      for investigation of how different cells types engage with and penetrate basement
      membrane, including research in angiogenesis, invasive cell migration, protease
      functions, and preclinical development of anti-invasive and anti-angiogenic
      agents. As novel mechanisms of metastasis and angiogenesis come to light and old
      paradigms are challenged, we examine how the assay can still provide innovative
      insights. We review established applications and variants of the matrigel
      invasion assay, highlight key findings derived from it and discuss future
      developments, including roles for accessory and cancer stem cells.

PMID- 20822889
TI  - Bodies of evidence - compartmentalization of the piRNA pathway in mouse fetal
      prospermatogonia.
AB  - Epigenetic reprogramming of embryonic mouse germ cells involves DNA demethylation
      of the genome that is accompanied by derepression of transposable elements (TEs).
      Threatening the genome's integrity, TE activation is efficiently countered by the
      concerted action of de novo DNA methylation and PIWI-interacting small RNAs
      (piRNAs). Recent studies have closely examined the subcellular localization of
      various piRNA pathway proteins in fetal prospermatogonia of wild-type and piRNA
      pathway mutant mice. Our survey highlights hierarchies and partnerships between
      the members of this ancient defensive mechanism. Overall, the elaborate
      cytoplasmic compartmentalization of the piRNA pathway in fetal prospermatogonia
      provides a highly informative context to aid our understanding of the mouse piRNA
      pathway.

PMID- 20822890
TI  - Tissue morphogenesis: how multiple cells cooperate to generate a tissue.
AB  - Genetic analysis in model organisms has recently achieved a detailed molecular
      description of many key cellular processes controlling embryonic morphogenesis.
      To understand higher order tissue morphogenesis, we now need to define how these
      processes become integrated across different cell groups and cell layers. Here,
      we review progress in this fast moving area, which was to a large degree made
      possible by novel imaging methods and the increasingly frequent use of modeling.
      Discussing examples from Caenorhabditis elegans and Drosophila embryos, two
      powerful and simple models, we highlight novel principles relying in part on
      mechanical tension, and outline the role of junctions as signal integrators.

PMID- 20822892
TI  - Frontiers of microscopy-based research into cell-matrix adhesions.
AB  - Focal adhesions (FAs) are highly dynamic multi-protein complexes, through which
      cells interact with the extracellular matrix (ECM) via integrin receptors. These
      large assemblies, which typically measure several micrometers in diameter,
      mediate interactions of cells with external surfaces, and are linked at their
      cytoplasmic faces with F-actin bundles. Over the last four decades, the molecular
      diversity of these adhesions and their roles in cell migration and matrix sensing
      have been extensively studied. Microscopy-based research is considered critical
      for characterizing and understanding the nature of these assemblies. Here, we
      review the contributions of, advanced microscopy to the characterization of the
      functional architecture of integrin-mediated, cell-matrix adhesions.

PMID- 20822891
TI  - Dynamic interplay between the collagen scaffold and tumor evolution.
AB  - The extracellular matrix (ECM) is a key regulator of cell and tissue function.
      Traditionally, the ECM has been thought of primarily as a physical scaffold that
      binds cells and tissues together. However, the ECM also elicits biochemical and
      biophysical signaling. Controlled proteolysis and remodeling of the ECM network
      regulate tissue tension, generate pathways for migration, and release ECM protein
      fragments to direct normal developmental processes such as branching
      morphogenesis. Collagens are major components of the ECM of which basement
      membrane type IV and interstitial matrix type I are the most prevalent. Here we
      discuss how abnormal expression, proteolysis and structure of these collagens
      influence cellular functions to elicit multiple effects on tumors, including
      proliferation, initiation, invasion, metastasis, and therapy response.

PMID- 20822893
TI  - The potential environmental gains from recycling waste plastics: simulation of
      transferring recycling and recovery technologies to Shenyang, China.
AB  - With the increasing attention on developing a low-carbon economy, it is necessary
      to seek appropriate ways on reducing greenhouse gas (GHG) emissions through
      innovative municipal solid waste management (MSWM), such as urban symbiosis.
      However, quantitative assessments on the environmental benefits of urban
      symbiosis, especially in developing countries, are limited because only a limited
      number of planned synergistic activities have been successful and it is difficult
      to acquire detailed inventory data from private companies. This paper modifies
      and applies a two-step simulation system and used it to assess the potential
      environmental benefits, including the reduction of GHG emissions and saving of
      fossil fuels, by employing various Japanese plastics recycling/energy-recovery
      technologies in Shenyang, China. The results showed that among various
      recycling/energy-recovery technologies, the mechanical waste plastics recycling
      technology, which produces concrete formwork boards (NF boards), has the greatest
      potential in terms of reducing GHG emissions (1.66 kg CO(2)e/kg plastics),
      whereas the technology for the production of refuse plastic fuel (RPF) has the
      greatest potential on saving fossil fuel consumption (0.77 kg ce/kg-plastics).
      Additional benefits can be gained by applying combined technologies that cascade
      the utilization of waste plastics. Moreover, the development of clean energy in
      conjunction with the promotion of new waste plastics recycling programs could
      contribute to additional reductions in GHG emissions and fossil fuel consumption.

PMID- 20822894
TI  - Potential use of densified polymer-pastefill mixture as waste containment barrier
      materials.
AB  - Mining activities generate a large amount of solid waste, such as waste rock and
      tailings. The surface disposal of such waste can create several environmental and
      geotechnical problems. Public perception and strict government regulations with
      regards to the disposal of such waste compel the mining industry to develop new
      strategies which are environmentally sound and cost effective. In this scenario,
      recycling of such waste into mining or civil engineering construction materials
      have become a great challenge for the mining and civil engineering community.
      Hence, in this study, taking advantage of the inherent low hydraulic conductivity
      of paste tailings (pastefill), small amounts (0.05, 0.1, 0.2, 0.5%) of a super
      absorbent polymer (SAP) are added to the latter after moisturizing the tailings.
      The resulting densified polymer-pastefill (PP) materials are compacted and
      submitted to permeability tests at room temperature and performance tests under
      cyclic freeze-thaw and wet-dry conditions to evaluate their suitability as a
      barrier for waste containment facilities. Valuable results are obtained. It is
      found that the hydraulic conductivity of the proposed barrier material (PP)
      decreases as the amount of SAP increases. Hydraulic conductivity values as low as
      1 * 10(-7) and 6 * 10(-9)cm/s are obtained for PPs which contain 0.1-0.5% SAP,
      respectively. The PP material also shows relatively good resistance to cyclic
      freeze-thaw and wet-dry stresses. The results show that negligible to acceptable
      changes in hydraulic conductivity occur after five freeze-thaw and six wet-dry
      cycles. None of the changes reach one order of magnitude. As a final step, a cost
      analysis is undertaken to evaluate the economical benefits that could be drawn
      from such a proposed barrier material. When compared to a conventional compacted
      sand-bentonite barrier with 12% bentonite concentration, it is found that the
      benefit realized could be estimated to 98, 96 and 90% when using PP material that
      contains 0.10, 0.20 and 0.5% of SAP. From this study, it can be concluded that PP
      materials show encouraging performance properties for barrier design.

PMID- 20822895
TI  - Pt nanoparticle label-mediated deposition of Pt catalyst for ultrasensitive
      electrochemical immunosensors.
AB  - Herein we describe a novel signal amplification strategy for the development of
      ultrasensitive electrochemical immunosensors. The amplification strategy is based
      on platinum catalyzing a hydrogen evolution reaction. To demonstrate its
      practicality, the electrochemical signal enhancement strategy has been applied
      for the development of a novel prostate-specific antigen (PSA) immunosensor. The
      immunosensing protocol utilized a gold electrode with PSA capture antibodies
      bound to its surface via covalent bonding. After PSA was bound to the electrode
      surface, a secondary platinum nanoparticle-labeled detection antibody was used to
      complete the sandwich immunosensor. The resulting electrode was then dipped in a
      platinum developer solution containing 1 mM of PtCl4(2-), 0.1M of formate
      (reductant) and 0.5% Tween 80 (pH 6.5) to generate bare platinum catalysts in
      close proximity to the Au electrode surface through a seed-mediated nucleation
      and growth mechanism. The signal readout was obtained electrochemically via a Pt
      catalyzed hydrogen evolution reaction in an acidic aqueous medium containing 10
      mM of HCl and 1 M of KCl. A detection limit of 1 fg/ml was achieved.

PMID- 20822896
TI  - The prevalence and burden of symptoms amongst cancer patients attending
      palliative care in two African countries.
AB  - BACKGROUND: The majority of cancer presentations in Africa are advanced and
      incurable, with incidence of malignancies projected to increase significantly.
      Despite the African cancer burden, almost nothing is known about the
      symptomatology of malignant progressive disease. This study aimed to determine
      the symptom prevalence and burden amongst advanced cancer patients in two African
      countries. METHODS: The Memorial Symptom Assessment Schedule Short Form (MSAS-SF)
      was used to measure the 7-d period prevalence and associated burden of
      multidimensional symptoms amongst adult patients attending palliative care in
      South Africa and Uganda. Further demographic and clinical variables were
      collected. RESULTS: Of the 112 patients recruited, 22 (19.6%) had an underlying
      HIV diagnosis. The most common cancer primaries were breast (N=24), cervix (N=21)
      and lung (N=14). The mean number of symptoms was 18 (SD=6.6). The five most
      prevalent symptoms were pain (87.5%), lack of energy (77.7%), feeling sad
      (75.9%), feeling drowsy (72.3%) and worrying (69.6%). The five symptoms ranked as
      most severe were as follows: pain n=26 (23.2%), sexual problems n=24 (21.4%),
      weight loss n=21 (18.8%), 'I don't look like myself'n=21 (18.8%) and lack of
      energy n=20 (17.9%). DISCUSSION: Pain and psychological problems were four of the
      five most common symptoms, found in more than 3 out of 4 patients. Our sample's
      reported mean number of symptoms was far higher than reported in other global
      studies. These data can inform the delivery of appropriate clinical care. The
      prevalence of multidimensional symptoms underlines the importance of holistic
      approaches to patient assessment and management, taking account of multiple and
      potentially interacting symptoms and locally appropriate intervention.

PMID- 20822897
TI  - Phase I evaluation of seliciclib (R-roscovitine), a novel oral cyclin-dependent
      kinase inhibitor, in patients with advanced malignancies.
AB  - AIM: Phase I study of seliciclib (CYC202, R-roscovitine), an inhibitor of cyclin
      dependent kinases 2, 7 and 9, causing cell cycle changes and apoptosis in cancer
      cells. PATIENTS AND METHODS: This phase I trial aimed at defining the toxicity
      profile, the maximum tolerated dose (MTD), the recommended phase II dose (RD) and
      the main pharmacokinetic and pharmacodynamic parameters of oral seliciclib. Three
      schedules were evaluated: seliciclib given twice daily for 5 consecutive days
      every 3 weeks (schedule A), for 10 consecutive days followed by 2 weeks off
      (schedule B) and for 3d every 2 weeks (schedule C). RESULTS: Fifty-six patients
      received a total of 218 cycles of seliciclib. Dose-Limiting Toxicities (DLT)
      consisting of nausea, vomiting, asthenia and hypokalaemia occurred at 1600 mg bid
      for schedule A and in schedule C, DLT of hypokalaemia and asthenia occurred at
      1800 mg bid. The evaluation of longer treatment duration in schedule B was
      discontinued because of unacceptable toxicity at lower doses. Other adverse
      events included transient serum creatinine increases and liver dysfunctions.
      Pharmacokinetic data showed that exposure to seliciclib and its carboxylate
      metabolite increased with increasing dose. Soluble cytokeratin 18 fragments
      allowed monitoring of seliciclib-induced cell death in the blood of patients
      treated with seliciclib at doses above 800 mg/d. One partial response in a
      patient with hepatocellular carcinoma and sustained tumour stabilisations were
      observed. CONCLUSIONS: The MTD and RD for seliciclib are 1250 mg bid for 5d every
      3 weeks and 1600 mg bid for 3d every 2 weeks, respectively.

PMID- 20822898
TI  - Diagnostic and prognostic role of plasma levels of two forms of cytokeratin 18 in
      patients with non-small-cell lung cancer.
AB  - PURPOSE: Cytokeratin 18 (CK18) can be used as a serum biomarker for carcinoma
      cell death, whereas caspase-cleaved (ccCK18) fragments reflect tumour apoptosis.
      We explored the potential diagnostic and prognostic role of circulating CK18 and
      ccCK18 in patients with non-small-cell lung cancer (NSCLC) in comparison with
      Cyfra 21.1, a fragment of cytokeratin 19. METHODS: Subject cohorts consisted of
      200 healthy blood donors (HBD), 113 patients with benign lung diseases (BLD) and
      179 NSCLC cases. Plasma levels of ccCK18, total CK18 and Cyfra 21.1 were
      determined with ELISA assays. RESULTS: Plasma levels of ccCK18 and total CK18
      were higher in the NSCLC group compared to the HBD and BLD cohorts (p<0.0001).
      Using a cut-off of 104 U/L for ccCK18 and 302 U/L for total CK18 (95% specificity
      in the HBD group) the diagnostic accuracy of both CK18 forms to distinguish
      between NSCLC and BLD cases was 56%, whereas it was 94% for Cyfra 21.1.
      Multivariate survival analysis showed that total CK18 was a stronger prognostic
      factor than both ccCK18 and Cyfra 21.1 (HR 0.64 for low versus high total CK18
      levels, 95% confidence interval (CI) 0.50-0.82; p=0.0004) in the entire NSCLC
      cohort and in 78 patients with locally advanced or metastatic disease treated
      with chemoradiotherapy or first-line chemotherapy (HR 0.70 95% CI 0.52-0.94;
      p=0.018). CONCLUSIONS: Cyfra 21.1 is a useful diagnostic biomarker for NSCLC.
      Total CK18 shows a promising potential as prognostic marker in NSCLC patients,
      independently of the therapeutical intervention. In contrast, ccCK18 was not of
      prognostic value in NSCLC, suggesting that tumour necrosis is of particular
      importance in this disease.

PMID- 20822899
TI  - Bioconversion of novel substrate Saccharum spontaneum, a weedy material, into
      ethanol by Pichia stipitis NCIM3498.
AB  - Rising fuel prices and environmental issues have paved the way for the
      exploration of cellulosic ethanol. However, challenges involving substrate
      hydrolysis and cost-effectiveness still limit the efficient bioconversion and
      utilization of cellulosic ethanol. We aimed to evaluate a cheaper and abundantly
      available wild sugarcane variety, Saccharum spontaneum, as the raw substrate for
      bioconversion of ethanol by Pichia stipitis NCIM3498. Three different strategies
      for substrate hydrolysis using acid (dilute sulfuric acid) and alkali (dilute
      sodium hydroxide) and aqueous ammonia (AA) treatment followed by enzymatic
      hydrolysis were studied. A maximum of 631.5+/-3.25 mg/g sugars with 89.38%
      hydrolytic efficiency (HE) could be achieved after enzymatic hydrolysis of AA
      pretreated S. spontaneum. All the substrate hydrolysates were evaluated for
      ethanol conversion in batches by P. stipitis. The microbial fermentation of
      released sugars into ethanol showed (g/g) 0.36+/-0.011, 0.384+/-0.022, 0.391+/
      0.02, and 0.40+/-0.01 yield from detoxified acid hydrolysate and acid-, NaOH- and
      AA-pretreated substrate S. spontaneum enzymatic hydrolysates, respectively.

PMID- 20822900
TI  - Improving the fermentability of enzymatic hydrolysates of lignocellulose through
      chemical in-situ detoxification with reducing agents.
AB  - Inhibitory lignocellulose hydrolysates were treated with the reducing agents
      dithionite and sulfite to achieve improved fermentability. Addition of these
      reducing agents (in the concentration range 5.0-17.5 mM) to enzymatic
      hydrolysates of spruce wood or sugarcane bagasse improved processes based on both
      SHF (simultaneous hydrolysis and fermentation) and SSF (simultaneous
      saccharification and fermentation). The approach was exemplified in ethanolic
      fermentations with Saccharomyces cerevisiae and by using hydrolysates with sugar
      concentrations>100 g/L (for SHF) and with 10% dry-matter content (for SSF). In
      the SHF experiments, treatments with dithionite raised the ethanol productivities
      of the spruce hydrolysate from 0.2 to 2.5 g*L(-1)*h(-1) and of the bagasse
      hydrolysate from 0.9 to 3.9 g*L(-1)*h(-1), values even higher than those of
      fermentations with reference sugar solutions without inhibitors. Benefits of the
      approach include that the addition of the reducing agent can be made in-situ
      directly in the fermentation vessel, that the treatment can be performed at a
      temperature and pH suitable for fermentation, and that the treatment results in
      dramatically improved fermentability without degradation of fermentable sugars.
      The many benefits and the simplicity of the approach offer a new way to achieve
      more efficient manufacture of fermentation products from lignocellulose
      hydrolysates.

PMID- 20822901
TI  - Structural basis for binding of cyclic 2-oxoglutarate analogues to factor
      inhibiting hypoxia-inducible factor.
AB  - Aromatic analogues of the 2-oxoglutarate co-substrate of the hypoxia-inducible
      factor hydroxylases are shown to bind at the active site iron: Pyridine-2,4
      dicarboxylate binds as anticipated with a single molecule chelating the iron in a
      bidentate manner. The binding mode of a hydroxamic acid analogue, at least in the
      crystalline state, is unusual because two molecules of the inhibitor are observed
      at the active site and partial displacement of the iron binding aspartyl residue
      was observed.

PMID- 20822902
TI  - The selected flavonol glycoside derived from Sophorae Flos improves glucose
      uptake and inhibits adipocyte differentiation via activation AMPK in 3T3-L1
      cells.
AB  - Among nine flavonols (1-9) obtained from Sophorae Flos, we first isolated
      compounds 4, 5, 8, and 9. These isolates (1-9) were evaluated for the
      phosphorylation of AMPK and ACC. Administered at 10 MUM, 9 possessed high potent
      activity. Compound 9 displayed a dose-dependent stimulation of glucose uptake in
      3T3-L1 cells, and this increase was obviously attenuated by compound C, an AMPK
      inhibitor. In addition, 9 also phosphorylated AMPK and its downstream substrate
      ACC in 3T3-L1 cells in a time- and dose-dependent manner. Moreover, we discovered
      that compound C inhibits 9-stimulated ACC phosphorylation and motivated the 9
      inhibited C/EBPalpha and PPARgamma, and FAS gene expression, significantly. These
      results revealed the role of the AMPK downstream signaling pathway in 9-improved
      glucose metabolism in 3T3-L1 cells and 9-inhibited adipocyte differentiation.
      Differentiation was investigated by Oil Red O staining activity after 9
      administration (0-20 MUM) in 6 days. Compound 9 decreased mean droplet size in a
      dose-dependent manner. The results revealed that 9 blocked adipogenic conversion
      in 3T3-L1 cells together with several significant downregulating adipocyte
      specific transcription factors, including PPARgamma, C/EBPalpha, and SREBP1. It
      also reduced FAS gene expression in a dose-dependent manner, which is crucial for
      adipogenesis in vitro.

PMID- 20822903
TI  - Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: structure
      activity relationship of the aryl region.
AB  - The structure-activity relationship of the prime region of hydroxyethylamine BACE
      inhibitors is described. Variation in the aryl linker region with 5- and 6
      membered heterocycles provided compounds such as 33 with improved permeability
      and reduced P-gp liability compared to benzyl amine analog 1.

PMID- 20822904
TI  - 3-alkylthio-1,2,4-triazine dimers with potent antimalarial activity.
AB  - We report on the discovery of 3-alkylthio-1,2,4-triazine dimers that are potently
      toxic to Plasmodium falciparum, with single digit nanomolar activity, and up to
      several thousand-fold lower toxicity to mammalian cells. They are equipotent
      against chloroquine-resistant strains of P. falciparum.

PMID- 20822905
TI  - Structure-based optimization of pyrazolo-pyrimidine and -pyridine inhibitors of
      PI3-kinase.
AB  - Starting from HTS hit 1a, X-ray co-crystallization and molecular modeling were
      used to design potent and selective inhibitors of PI3-kinase. Bioavailablity in
      this series was improved through careful modulation of physicochemical
      properties. Compound 12 displayed in vivo knockdown of PI3K pharmacodynamic
      markers such as pAKT, pPRAS40, and pS6RP in a PC3 prostate cancer xenograft
      model.

PMID- 20822906
TI  - A stereo-controlled synthesis of 2,4-dimethyl-4-hydroxy-16-phenylhexadecanoic
      acid 1,4-lactone and its PPAR activities.
AB  - A novel class of natural PPAR agonists, 2,4-dimethyl-4-hydroxy-16
      phenylhexadecanoic acid 1,4-lactone (1), were discovered in marine natural
      product libraries. The synthesis of 1 was accomplished starting from vinylmethyl
      ketone. Ring formation of the alpha,gamma dialkyl gamma-lactone was achieved via
      the stereo-controlled reaction of a ketyl radical anion with a chiral
      methacrylate. In the PPAR agonistic assay, the most potent of the four
      stereoisomers had EC(50) values of 12 MUM for mPPARalpha, 9 MUM for mPPARdelta
      and >100 MUM for mPPARgamma.

PMID- 20822907
TI  - Synthesis of biologically active biotinylated muramyl dipeptides.
AB  - Muramyl dipeptide (MDP) is believed to interact with an innate immune receptor,
      Nod2. To identify the cellular receptor for MDP, we have synthesized biotinylated
      MDP isomers and tested the ability of these compounds to activate Nod2 in a cell
      based assay. We found that the modification of MDP does not perturb its ability
      to activate Nod2. These tagged versions of MDP will be useful to identify the
      cellular receptor of the immunostimulatory molecules.

PMID- 20822908
TI  - Expression of platelet-derived growth factor ligand and receptor in cerebral
      arteriovenous and cavernous malformations.
AB  - The aim of this study was to investigate the expression of platelet-derived
      growth factor (PDGF) ligands A and B and receptors alpha and beta in cerebral
      arteriovenous and cavernous malformations. Fifteen arteriovenous malformation
      (AVM) and 15 cerebral cavernous malformation (CCM) tissue samples were
      immunostained for PDGF ligands A and B, PDGF receptors (PDGFR) alpha and beta,
      and vascular endothelial growth factor. Tissues were compared in terms of
      expression levels within various vascular layers, and the results were confirmed
      using western blotting. AVM had higher levels of PDGF-A expression than CCM (p =
      0.004, 0.009, 0.001, and 0.027, for endothelium, media, adventitia, and
      perilesional tissue, respectively) and western blotting showed that there was
      higher expression of PDGFR-alpha in AVM tissues. In contrast, CCM endothelium,
      media, and adventitia had higher PDGF-B expression compared with AVM (p = 0.007,
      0.001, and 0.039, respectively). PDGFR-beta expression was also significantly
      higher in the endothelium of CCM tissue (p = 0.007). Overexpression of PDGF
      ligands and receptors in AVM and CCM may mean that therapeutic strategies
      targeting the PDGF pathway could be useful in the treatment of these two
      malformations.

PMID- 20822909
TI  - The rs522616 polymorphism in the matrix metalloproteinase-3 (MMP-3) gene is
      associated with sporadic brain arteriovenous malformation in a Chinese
      population.
AB  - In this study, we investigated the association between common variants in the
      matrix metalloproteinase-3 (MMP-3) gene and the risk of developing sporadic brain
      arteriovenous malformation (BAVM). We performed genotyping analyses for five
      single nucleotide polymorphisms (SNPs) in MMP-3 in a case-control study involving
      319 Chinese patients with BAVM and 333 Chinese controls. The association between
      MMP-3 genotypes and the risk of developing BAVM was evaluated using logistic
      regression analyses. We found that the genotype frequencies were significantly
      different between patients and controls for the rs522616 A > G variant of MMP-3
      (p = 0.02). Logistic regression analysis revealed that the variant genotype of
      this polymorphism was associated with a significantly decreased risk of BAVM
      (adjusted odds ratio = 0.62, 95% confidence interval = 0.44-0.87, p = 0.006 for
      the AG compared with the AA genotype; adjusted odds ratio=0.68, 95% confidence
      interval = 0.49-0.94, p = 0.019 for the AG + GG compared with the AA genotype).
      These findings indicate for the first time that the MMP-3 rs522616 polymorphism
      may contribute to the etiology of sporadic BAVM in the Chinese population.

PMID- 20822910
TI  - Implications for immunotherapy of tumor-mediated T-cell apoptosis associated with
      loss of the tumor suppressor PTEN in glioblastoma.
AB  - The ability of glioma cells to escape the immune system remains a significant
      barrier to successful immunotherapy. Here we demonstrate that loss of the PTEN
      tumor suppressor gene, with associated activation of the PI3K/Akt/mTOR pathway,
      leads to a human glioma phenotype that induces autologous T-cell apoptosis upon
      contact. The PTEN status of pathologically confirmed glioblastoma specimens was
      defined, and primary cultures established after surgical resection of tumor from
      26 patients. Autologous T-cells were isolated from these patients, and after T
      cell activation was induced, these cells were co-cultured with matched autologous
      glioma cells, either alone, or after treatment with one of three inhibitors of
      the PI3K/Akt/mTOR pathway. When co-cultured with autologous T-cells, PTEN wild
      type tumor cells induced apoptosis in a minimal number of activated T-cells (6
      12% of T-cells), whereas tumors with PTEN loss induced much more profound levels
      of T-cell apoptosis (42-56% of T-cells). Prior treatment of PTEN-deficient tumor
      cells with specific inhibitors of the PI3K/Akt/mTOR pathway diminished T-cell
      apoptosis to levels seen after co-culture with wild-type PTEN tumor cells,
      suggesting that PTEN loss confers this immunoresistant phenotype through the
      PI3K/Akt/mTOR pathway. These results suggest that PTEN-deficient glioblastoma
      patients are suboptimal candidates for immunotherapy. In addition, our results
      raise the possibility of combining T-cell based immunotherapy protocols with
      clinical inhibitors of the PI3K/Akt/mTOR pathway.

PMID- 20822911
TI  - Secondary signs on static stress MRI in anterior cruciate ligament rupture.
AB  - The MRI diagnosis of ACL rupture based on primary signs has variable rates of
      diagnostic accuracy. These signs observed on direct visualisation of the ACL
      include discontinuity of fibres, abnormal ligament contour and increased
      intrasubstance signal intensity. Secondary radiological signs of ACL rupture are
      increasingly being used. These indirect ancillary signs include PCL angle,
      translocation of the tibia relative to the femur and displacement of the
      posterior horns of the menisci. The aim of this study was to investigate if the
      application of static stress force to the knee will accentuate the secondary
      signs of ACL rupture on MRI. One hundred and forty-eight subjects (50 subjects
      with arthroscopically confirmed ACL rupture, 48 subjects with arthroscopically
      confirmed intact ACL and 50 subjects with clinically confirmed normal knees)
      underwent MRI of their knee with the application of specially designed fibreglass
      leg splints which exert a translational force on the knee joint. Five secondary
      radiological signs were evaluated and all were found to be significantly
      accentuated following the application of the splints (p<0.001). The MRI diagnosis
      of ACL rupture demonstrated a sensitivity of 95.9%, specificity of 91.7% and
      accuracy of 93.8%. The static stress technique improved the accuracy of
      diagnosing ACL ruptures on MRI and illustrated the abnormal tibiofemoral
      kinematics.

PMID- 20822912
TI  - OGA inhibition by GlcNAc-selenazoline.
AB  - The title compound, which differs from the powerful O-GlcNAcase (OGA) inhibitor
      GlcNAc-thiazoline only at the chalcogen atom (Se for S), is a much weaker
      inhibitor in a direct OGA assay. In human cells, however, the selenazoline shows
      comparable ability to induce hyper-O-GlcNAc-ylation, and the two show similar
      reduction of insulin-stimulated translocation of glucose transporter 4 in
      differentiated 3T3 adipocytes.

PMID- 20822914
TI  - Characterization of FaSPT, a SPATULA gene encoding a bHLH transcriptional factor
      from the non-climacteric strawberry fruit.
AB  - The involvement of basic-helix-loop-helix (bHLH) transcription factors in
      essential physiological and developmental processes is well established. Although
      a lot of animal bHLH proteins were characterized functionally, much less bHLHs of
      plant origin have been studied so far. Using a cDNA-AFLP approach, a ripening
      related SPATULA gene was identified from strawberry fruit (Fragaria * ananassa
      Duch.), which encodes a bHLH protein. It is an orthologue of an Arabidopsis
      SPATULA protein, which has an important role in carpel and fruit development. Our
      experiments revealed that FaSPT is repressed by auxin in green fruits, and shows
      different expression patterns in receptacles at various stages of fruit ripening
      by ethylene treatment. Moreover, we applied a reverse genetic tool to elucidate
      the in planta function of FaSPT in early fruit development. To our knowledge,
      this work is the first report for the characterization of a SPATULA gene from a
      non-climacteric fruit.

PMID- 20822913
TI  - Study of oxidative stress related responses induced in Arabidopsis thaliana
      following mixed exposure to uranium and cadmium.
AB  - In this study, toxicity effects in plants of uranium in a binary pollution
      condition were investigated by studying biological responses and unraveling
      oxidative stress related mechanisms in Arabidopsis thaliana seedlings, grown on
      hydroponics and exposed for 3 days to 10 MUM uranium in combination with 5 MUM
      cadmium. While uranium mostly accumulated in the roots with very low root-to
      shoot transport, cadmium was taken up less by the roots but showed higher
      translocation to the shoots. Under mixed exposure, cadmium influenced uranium
      uptake highly but not the other way round resulting in a doubled uranium
      concentration in the roots. Under our mixed exposure conditions, it is clear that
      micronutrient concentrations in the roots are strongly influenced by addition of
      cadmium as a second stressor, while leaf macronutrient concentrations are mostly
      influenced by uranium. Oxidative stress related responses are highly affected by
      cadmium while uranium influence is more limited. Hereby, an important role was
      attributed to the ascorbate redox balance together with glutathione as both
      metabolites, but more explicitly for ascorbate, increased their reduced form,
      indicating an important defense and regulatory function. While for roots, based
      on an increase in FSD1 gene expression, oxidative stress was suggested to be
      superoxide induced, in leaves on the other hand, hydrogen peroxide related genes
      were mostly altered.

PMID- 20822915
TI  - Correction of secondary vermilion notching deformity in unilateral cleft lip
      patients: complete revision of two errors.
AB  - BACKGROUND: Vermilion notching deformity is one of the most common secondary
      deformities in unilateral cleft lip patients. Two errors during primary
      cheiloplasty seem to cause notching deformity. The first one is insufficiently
      lengthened oral lining of the medial lip compared to the cutaneous surface, and
      the other is medialized marking of the height of cupid's bow on cleft side rather
      than marking it at the thickest portion of the vermilion. The authors were able
      to obtain satisfactory results after revising notching deformities by correcting
      these two errors. METHODS: A total of 104 patients (median age: 13) with
      secondary notching deformity underwent revision surgery from 1987 to 2009. After
      the new height of cupid's bow on the cleft side was marked on the white roll with
      the greatest vermilion fullness, the notched vermilion including the cutaneous
      scar was elevated. For sufficient lengthening of the oral lining, the elevated
      tissue was interposed as an inferior pedicled flap into a relaxing incision of
      the central portion of the oral sulcus. RESULTS: The follow-up period ranged from
      1 year to 12 years. The patients were satisfied with the aesthetic outcomes.
      Seven patients experienced lateral vermilion bulging which was easily corrected
      by an elliptical excision. CONCLUSION: Complete revision by lengthening the oral
      lining of the central lip portion, and lateralizing the height of cupid's bow of
      cleft side to the region where vermilion is thickest, is an effective method for
      correction of secondary notching deformity.

PMID- 20822916
TI  - Autologous fat transfer to the cranio-maxillofacial region: updates and
      controversies.
AB  - BACKGROUND: Autologous fat grafts have gained popularity among Cranio
      Maxillofacial surgeons within the past years. Most publications report favourable
      outcomes but lack quantifiable evidence of graft survival. OBJECTIVES: To assess
      autologous fat transfer for facial asymmetry, and review the literature focusing
      on current indications, techniques, complications, fat survival and patient
      satisfaction. PATIENTS AND METHODS: Nine patients presented facial asymmetry due
      to onchological resection, congenital anomaly, or craniofacial traumatism. A
      total of 11 autologous fat transfers were performed. Four procedures followed the
      Coleman technique; in the other seven procedures, fat centrifugation was
      obviated. RESULTS: No significant complications derived. Progressive volumetric
      decrease was evidenced for up to 6 months after surgery. A second procedure was
      performed in two patients. No clinical differences in cosmetic outcomes or graft
      survival were observed between centrifuged and non-centrifuged grafts. Patients
      reported high satisfaction. CONCLUSIONS: Facial recontouring with autologous fat
      transfer restores volumetric defects with high patient satisfaction. The
      scientific literature offers inconsistent results. The authors did not find
      clinical differences between centrifuged and non-centrifuged grafts. Volume gain
      may result from induced fibrosis, inflammation and native adipocyte growth or
      differentiation. The heightened interest in these procedures should instigate
      further investigation to refine surgical procedures and improve predictability.

PMID- 20822917
TI  - Cystic fibrosis and the thoracic surgeon.
AB  - Indications for thoracic surgery in patients with cystic fibrosis (CF) are
      principally represented by pleural diseases including pneumothorax, pleural
      effusion, and empyema and by parenchymal lung diseases including bronchiectasis,
      hemoptysis, and pulmonary abscess. Moreover, lung transplantation has proved a
      viable therapeutic option for progressive respiratory failure due to end-stage
      CF. Main surgical experiences in this setting are reviewed and discussed.

PMID- 20822918
TI  - Effect of walking speed and severity of hip osteoarthritis on gait variability.
AB  - Gait analysis in orthopaedic and neurological examinations is important; however,
      few studies assess gait variability at different walking speeds in patients with
      varying degrees of hip osteoarthritis. We aimed to clarify (1) how different
      controlled speeds and (2) various severities of hip osteoarthritis influence gait
      variability. Gait variability was described by the standard deviation (SD) of the
      spatial-temporal and mean standard deviation (MeanSD) of angular parameters. The
      spatial positions of the anatomical points for calculating gait parameters were
      determined in 20 healthy elderly controls and 20 patients with moderate and 20
      patients with severe hip osteoarthritis with a zebris CMS-HS ultrasound-based
      motion analysis system at three walking speeds. The SD of the spatial-temporal
      and MeanSD of angular parameters of gait, which together describe gait
      variability, significantly depended on speed and osteoarthritis severity. The
      lowest variability in the gait was found near the self-selected walking speeds.
      Hip joint degeneration significantly worsened variability on the affected side,
      with non-affected joints and the pelvis compensating by increasing flexibility
      and adapting to step-by-step motions. Particular attention must be paid to
      improving gait stability and the reliability of limb movements in the presence of
      and increasing severity of osteoarthritis.

PMID- 20822919
TI  - A double-orifice, severely stenotic aortic valve: is leaflet perforation or
      extensive central calcification with near fusion the culprit?

PMID- 20822920
TI  - Behcet's disease and heart transplantation: a word of caution.
AB  - Behcet's disease is a rare autoimmune disease characterized by oral and genital
      ulcers, and by multisystem disease, including arthritis, neurologic complications
      and vasculitis. Large-vessel and coronary artery aneurysms are often an
      indication for surgery, but the return of aneurysms, thrombosis, and the tendency
      to exhibit an exaggerated inflammatory response at puncture sites (pathergy)
      complicate surgical recovery. As such, cardiac transplantation, which requires
      atrial and large-vessel anastomoses, has not been reported in patients with
      Behcet's disease. We report the first orthotopic heart transplant with >1-year
      survival in a patient with Behcet's disease despite major complications. The
      investigators remain pessimistic about cardiac transplantation in patients with
      Behcet's disease until advances in preventing recurrent vascular pathology ensue.

PMID- 20822921
TI  - Metastatic epithelioid sarcoma in a non-healing ventricular device pocket.

PMID- 20822922
TI  - Prevention of primary graft dysfunction in lung transplantation by N
      acetylcysteine after prolonged cold ischemia.
AB  - BACKGROUND: N-Acetylcysteine (NAC), a thiol-containing compound that has been
      used as an anti-oxidant, may also lead to an increased glutathione synthesis.
      This study assessed the protective effect of NAC on primary graft dysfunction
      after lung transplantation. METHODS: Porcine single left-lung transplantation was
      performed in 2 experimental groups after 24 hours of cold storage. Donor and
      recipient animals were treated with intravenous injection of 150 mg/kg NAC 60
      minutes before harvest and reperfusion, followed by 12.5 mg/kg/hour continuous
      perfusion during the 8-hour observation period (NAC). Control animals did not
      receive any treatment. Hemodynamic and respiratory parameters were recorded
      throughout the observation period. Bronchoalveolar lavage (BAL) nitrite,
      neutrophil elastase (NE), protein accumulation, interleukin (IL)-8, nuclear
      factor-kappaB (p50 sub-unit), and reduced glutathione (GSH) in lung tissue and
      red blood were measured. RESULTS: During the observation period, the mean
      pulmonary artery pressure, oxygenation, airway pressure, and static lung
      compliance were significantly better in NAC animals compared with controls (p <
      0.05). Extravascular lung water index was higher at points during the reperfusion
      in the control group. BAL protein, nitrite, NE, and IL-8 cytokine levels at the
      end of the experiment were significantly higher in the controls than in the NAC
      group (p < 0.05). Lung tissue reduced GSH levels were significantly higher in the
      NAC group than in the control group. Red blood cell GSH levels were always higher
      in the NAC group during the reperfusion period. Reverse transcription polymerase
      chain reaction for IL-8 messenger RNA was significantly higher in controls during
      the reperfusion period than in the NAC group (p = 0.001). The amount of lung
      tissue nuclear NF-kappaB (p50 sub-unit) was significantly higher in controls than
      in NAC pigs (p = 0.03). CONCLUSION: In this model, donor and recipient treatment
      with NAC effectively protected the lung from primary graft dysfunction after
      prolonged cold ischemia.

PMID- 20822923
TI  - H1N1 influenza vaccination and infection in pediatric heart transplants.

PMID- 20822924
TI  - Survey of current practice related to grading of rejection in cardiac transplant
      recipients in North America.
AB  - BACKGROUND: The acceptance and implementation of the International Society for
      Heart and Lung Transplantation's most recently adopted grading system (ISHLT
      2004), which supplanted the ISHLT-1990 system for diagnosing cardiac allograft
      rejection, are unknown. METHODS: We performed an online survey of pathologists at
      cardiac transplant centers in the United States and Canada to determine how
      cardiac transplant rejection is reported. The survey consisted of a series of
      questions related to biopsy volume, the rejection grading system used, and
      reasons why that grading system was used. RESULTS: Survey responses were obtained
      from 96 of 122 centers in the United States and Canada. Eighty-seven percent of
      respondents reported adopting the ISHLT-2004 grading system, either exclusively
      or in combination with other grading systems. Overall, 45% of respondents use
      only the ISHLT-2004 grading system, 40% issue reports containing both the ISHLT
      2004 and the ISHLT-1990 grading systems, 12% use only the ISHLT-1990 system, and
      3% use either the ISHLT-2004 or the ISHLT-1990 system in combination with an
      older scoring system. The primary reasons for not using the ISHLT-2004 grading
      system exclusively were (1) the perceived preference of cardiologists and cardiac
      surgeons at that particular center (77%) and (2) a belief that the ISHLT-2004
      grading system is not as informative as the ISHLT-1990 grading system (62%).
      CONCLUSIONS: There is appreciable variability in the system(s) used for reporting
      rejection among North American cardiac transplant centers. Understanding the
      reasons behind this variability will be crucial for the optimization of future
      grading systems for cardiac allograft rejection.

PMID- 20822926
TI  - The role of survivin and Bcl-2 in zinc-induced apoptosis in prostate cancer
      cells.
AB  - OBJECTIVES: To study the effects of zinc treatment on the gene expression levels
      of survivin and Bcl-2 in prostate cancer cells. MATERIALS AND METHODS: The
      effects of zinc exposure on apoptosis were assessed using two human prostate
      cancer cell lines, LNCaP and PC-3. Zinc-induced apoptosis was measured by Annexin
      V staining. The direct effect of zinc on the expression levels of zinc
      transporters (ZnT-1 and ZnT-4) and apoptosis-related genes (Bax, Bcl-2, and
      survivin) was determined by RT-PCR analysis. RESULTS: When LNCaP and PC-3 cells
      were exposed to various concentrations of zinc sulfate for 48 hors, their growth
      was inhibited in a dose-dependent manner. The levels of zinc in both cell lines
      treated with zinc sulfate for 24 hours were higher than in untreated cells.
      Exposure to zinc induced apoptosis and necrosis in LNCaP and PC-3 cells.
      Apoptosis became more extensive as the treatment time with zinc increased. There
      was a significant increase in the gene expression levels of ZnT-1 and ZnT-4 in
      both cell lines treated with zinc sulfate compared with untreated cells. The
      expression of Bax mRNA was up-regulated, while the expression of Bcl-2 and
      survivin were decreased in both cell lines following zinc treatment. CONCLUSIONS:
      Exposure to zinc sulfate in human prostate cancer cells increased intracellular
      levels of zinc, which resulted in increased apoptosis. The apoptogenic effect of
      elevated concentration of zinc could be due either to increased expression of
      zinc transporters and increased levels of Bax or decreased Bcl-2 and survivin
      expression.

PMID- 20822927
TI  - Serum tumor markers in testicular cancer.
AB  - Testicular cancer has become a model for a curable neoplasm, where biochemical
      markers play a critical role. Serum tumor markers are integral in patient
      management and contributes to the diagnosis, staging, and risk assessment, as
      well as evaluation of response to therapy and detection of relapse. We review
      their biochemistry, biology, and clinical use in the setting of localized and
      metastatic disease. The integration of tumor markers in prognostic models as well
      as the significance of marker kinetics during chemotherapy is discussed.

PMID- 20822928
TI  - Oncogenic role of fibroblast growth factor receptor 3 in tumorigenesis of urinary
      bladder cancer.
AB  - Bladder cancer is the second most common genitourinary tumor and constitutes a
      very heterogeneous disease. Molecular and pathologic studies suggest that low
      grade noninvasive and high-grade invasive urothelial cell carcinoma (UCC) arise
      via distinct pathways. Low-grade noninvasive UCC represent the majority of tumors
      at presentation. A high proportion of patients with low-grade UCC develop
      recurrences but usually with no progression to invasive disease. At presentation,
      a majority of the bladder tumors (70%-80%) are low-grade noninvasive (pTa).
      Several genetic changes may occur in bladder cancer, but activating mutations in
      the fibroblast growth factor receptor 3 (FGFR3) genes are the most common and
      most specific genetic abnormality in bladder cancer. Interestingly, these
      mutations are associated with bladder tumors of low stage and grade, which makes
      the FGFR3 mutation the first marker that can be used for diagnosis of noninvasive
      bladder tumors. Since the first report of FGFR3 involvement in bladder tumors,
      numerous studies have been conducted to understand its function and thereby
      confirm the oncogenic role of this receptor particularly in noninvasive groups.
      Efforts are on to exploit this receptor as a therapeutic target, which holds much
      promise in the treatment of bladder cancer, particularly low-grade noninvasive
      tumors. Further studies need to explore the potential use of FGFR3 mutations in
      bladder cancer diagnosis, prognosis, and in surveillance of patients with bladder
      cancer. This review focuses on the role of FGFR3 in bladder tumors in the
      backdrop of various studies published.

PMID- 20822929
TI  - The effect of minimally invasive and open radical prostatectomy surgeon volume.
AB  - OBJECTIVE: To determine the effect of minimally invasive radical prostatectomy
      (MIRP) surgeon volume on outcomes, and correlate with those of open radical
      prostatectomy retropubic (ORP). METHODS AND MATERIALS: Observational population
      based study of 8,831 men undergoing MIRP and ORP by 1,457 low, medium, and high
      volume surgeons from SEER-Medicare linked data from 2003 to 2007. After
      stratifying by surgeon ORP and MIRP volume, the following outcomes were studied:
      length of stay, transfusions, post-operative 30-day and anastomotic stricture
      complications, and use of additional cancer therapies. RESULTS: Men undergoing
      MIRP with high and medium vs. low volume surgeons were less likely to require
      additional cancer therapies (4.5% and 4.7% vs. 7%, P = 0.020). Similarly, men
      undergoing ORP with high vs. medium and low volume surgeons were less likely to
      require additional cancer therapies (5.7% vs. 6.8% and 7.1%, P = 0.044). Men
      undergoing ORP with high vs. medium and low volume surgeons experienced shorter
      lengths of stay (2.9 vs. 3.3 and 3.6 days, P < 0.001), and fewer transfusions
      (15.4% vs. 21.3% and 22.7%, P = 0.017), 30-day complications (18.4% vs. 25.6% and
      25.7%, P < 0.001), and anastomotic strictures (10.1% vs. 15.6% and 16.3%, P =
      0.003). However, MIRP surgeon volume did not affect these outcomes. CONCLUSIONS:
      Men undergoing MIRP or ORP with high volume surgeons were less likely to require
      additional cancer therapies. Additionally, patients of high volume ORP surgeons
      were more likely to experience shorter hospital stays, fewer transfusions, 30-day
      complications, and anastomotic strictures, while MIRP surgeon volume did not
      affect these peri-operative outcomes.

PMID- 20822931
TI  - To the editor: response to Barlow et al, Urol Oncol 2010.

PMID- 20822930
TI  - External validation of the cancer of the prostate risk assessment (CAPRA) score
      in a single-surgeon radical prostatectomy series.
AB  - OBJECTIVES: Prostate cancer clinical staging has significant limitations in the
      ability to accurately risk-stratify patients for prompt treatment or expectant
      management. The University of California San Francisco Cancer of the Prostate
      Risk Assessment (UCSF CAPRA) was recently described as a straightforward staging
      system that uses clinical variables to generate a score ranging from 0 to 10. Our
      objective was to perform an external validation of the CAPRA score as a predictor
      of 5-year progression-free survival (PFS) in a single-surgeon radical retropubic
      prostatectomy (RRP) series. MATERIALS AND METHODS: We examined the performance
      characteristics of the preoperative CAPRA score (0-10) to predict biochemical
      progression-free survival (PFS) in 990 men who underwent RRP by a single surgeon
      from 2003 to 2009. RESULTS: CAPRA scores were significantly associated with the
      risk of early biochemical progression in our series. For example, 5-year PFS was
      markedly different for scores at the extremes of 0 to 1 vs. >=7 (95% vs. 40%,
      respectively). The concordance index was 0.764 for the prediction of biochemical
      progression using CAPRA scores in this cohort, which compares favorably with the
      concordance index of 0.66 in the original CaPSURE dataset. CONCLUSIONS: Our
      results validate the UCSF-CAPRA score as a significant predictor of 5-year PFS in
      a single surgeon series. The CAPRA score is a simple preoperative tool that can
      be readily applied in clinical practice to help risk-stratify prostate cancer
      patients.

PMID- 20822932
TI  - Recurrent seminomas: clinical features and biologic implications.
AB  - OBJECTIVES: Certain patients with seminoma and clinically atypical phenotypes-
      visceral metastases, elevated levels of beta human chorionic gonadotropin
      (betaHCG), and/or recurrent disease--have a poor prognosis. The primary goal of
      this pilot study was to characterize the clinical characteristics and treatment
      profile of these rare patients. We also wished to test whether these tumors
      expressed any specific biomarkers that might distinguish them as a unique subtype
      of seminoma. MATERIALS AND METHODS: We retrospectively identified 25 patients
      with a history of seminoma plus visceral metastases, betaHCG levels >200 mU/ml,
      and/or recurrent disease. We reviewed these patients' histories for treatment
      efficacy and clinical outcome. Tissue samples were available from 6 of those
      patients, and we studied them for expression of the markers OCT 3/4, PLAP, CD30,
      TRA-1-60, c-kit, and gp200. We compared our results with the expression of those
      markers in tissue samples from mixed seminoma/embryonal carcinomas and classic
      seminomas. RESULTS: Our analysis suggested that certain chemotherapeutic regimens
      (such as ifosfamide, paclitaxel, and cisplatin) are efficacious for the treatment
      of patients with these atypical seminomas. Further, specimens from the atypical
      seminomas generally had staining profiles that resembled those of classic
      seminomas and the seminoma components in mixed germ-cell tumors, but the profiles
      differed from those of the embryonal carcinoma components in the same mixed germ
      cell tumors. CONCLUSIONS: Although these atypical seminomas tend to be resistant
      to chemotherapy, they may still respond to certain chemotherapeutic regimens. Our
      pilot immunohistochemical study also suggested that the unique phenotypes
      associated with these atypical seminomas do not result from any relationship with
      embryonal carcinomas. More study is needed to confirm these initial findings.

PMID- 20822933
TI  - Are cell cycle and apoptosis genes associated with prostate cancer risk in North
      Indian population?
AB  - OBJECTIVE: Prostate cancer (CaP) is a heterogeneous, multifactorial, and
      multifocal disease. Therefore, the search for a combination of functional
      polymorphisms using cell cycle and apoptotic genes as tumor markers is
      fundamental for a more precise and reliable diagnosis. In the present study, we
      investigated the diagnostic value of 3 different genes associated with CaP
      carcinogenesis, encoding for cell cycle (MDM2, CCND1) and apoptotic (Fas) genes
      that are differentially expressed in CaP. METHODS: In a hospital-based case
      control study of northern India, blood samples were obtained from 192 CaP
      patients and 224 cancer-free age matched unrelated healthy controls of similar
      ethnicity. They were genotyped for MDM2 G309T, CCND1 G870A, Fas A670G, and G1377A
      polymorphisms using polymerase chain restriction fragment length polymorphism
      (PCR-RFLP) method. RESULTS: MDM2 309GG variant was at reduced risk for developing
      CaP (P = 0.041; OR, 0.59). Whereas CCND1 AA genotype demonstrated increased risk
      (P = 0.018; OR, 1.86). The diplotype analysis of Fas G670A and G1377A (G-A) was
      observed to be associated with a significant increase in CaP risk (P = 0.024; OR,
      1.63). CONCLUSION: Findings based on current sample size our results suggested a
      positive association of CCND1AA genotype and diplotype analysis of Fas G670A and
      G1377A (G-A) to be associated with CaP risk that could influence the
      pathophysiology, thereby modulating the risk of CaP.

PMID- 20822934
TI  - Prostate cancer: evidence-based indications for postoperative radiotherapy.

PMID- 20822935
TI  - CA9 as a molecular marker for differential diagnosis of cystic renal tumors.
AB  - OBJECTIVE: CA9 is proven to be a powerful marker for clear cell renal cell
      carcinoma. The studies on CA9 have been limited to solid renal cell carcinomas
      (RCC). We have conducted a study of CA9 expression in renal cystic tumors. The
      purpose of the present study was to extend the utility of CA9 for cystic renal
      tumors. MATERIALS AND METHODS: Immunohistochemistry and enzyme-linked
      immunosorbent assay (ELISA) were used to detect CA9 expression in cystic renal
      tumors. Forty-three cystic renal tumors (22 benign and 21 malignant) were
      included for the immunohistochemical staining. Thirty-six patients with a cystic
      renal mass (20 malignant and 16 benign cystic tumors) were studied to measure CA9
      level in the fluid by ELISA. Sixteen cysts (9 malignant and 7 benign cysts) were
      subjected both to immunohistochemistry and CA9 measurement in the fluid. RESULTS:
      Using immunohistochemical staining, all the benign cystic renal tumors including
      the 18 simple cyst and 4 benign multilocular cystic nephromas did not express
      CA9. All 13 cystic clear cell RCC were scored as strong staining for CA9. For 8
      multilocular clear cell RCC, 7 were scored as strong staining for CA9 and the
      other one was negative. There was a significant difference in positive percentage
      (P < 0.001) between the 2 groups of malignant and benign cysts. For the 16 benign
      cysts, the mean concentration of CA9 in the fluid of cyst was 162 +/- 133 pg/ml
      (median: 0 pg/ml; range: 0-2140 pg/ml). For the 20 malignant renal cystic tumors,
      the mean concentration of CA9 in the fluid of cyst was 2043 +/- 62 pg/ml (median:
      2,140 pg/ml; range: 1,112-2,140 pg/ml). There was a significant difference in
      mean concentration of CA9 between the two groups of malignant and benign cysts (P
      < 0.001). The presence or absence of CA9 expression measured by
      immunohistochemistry and ELISA test was concordant in 14 out of 16 cases (88%).
      CONCLUSIONS: Malignant cystic renal tumors expressed strongly CA9 while the
      benign renal cysts did not express CA9. CA9 can be detected in the fluid of
      malignant cystic renal tumors. CA9 is a promising molecular marker to
      differentiate the malignant cystic renal tumors from the benign cysts.

PMID- 20822936
TI  - Effects of age and immune suppression of sheep on fecundity, hatching and larval
      feeding of different strains of Haemonchus contortus.
AB  - The effects of host age and immune suppression on abomasal parasitic infection in
      sheep were investigated following single experimental oral infections with MHco3
      (ISE), MHco4 (WRS) and MHco10 (CAVR) strains of Haemonchus contortus in naive 5
      month-old crossbred lambs (n=1 per group) and 15-month-old Greyface sheep treated
      with methyl prednisolone acetate (n=2 per group) or without corticosteroid
      treatment (n=2 per group). Adult female H. contortus in 5-month-old lambs (n=1
      per group) shed on average 6.5, 3.1 and 8.0 times more eggs than in 15-month-old
      sheep (n=4 per group) following infection with MHco3 (ISE), MHco4 (WRS) and
      MHco10 (CAVR) strains of H. contortus, respectively, over a period of 28 days
      following the commencement of patency. There was no obvious effect of age of
      sheep or corticosteroid treatment on the abomasal establishment of H. contortus
      or on in vitro assays for egg hatching or larval feeding at different
      concentrations of anthelmintics, although statistical analysis could not be
      performed due to the small group sizes.

PMID- 20822937
TI  - Canine ischaemic stroke: current status and future directions.

PMID- 20822938
TI  - Multinucleated giant cells with an osteoclast phenotype derived from caprine
      peripheral blood mononuclear cells.
AB  - Formation of multinucleated giant cells (MGCs) by macrophage fusion is a typical
      cytopathic effect of lentiviral replication in caprine monocytes and MGC
      formation from cultured caprine peripheral blood mononuclear cells (PBMCs) has
      been considered to be diagnostic for small ruminant lentivirus (SRLV) infection.
      In this study, formation of MGCs was observed after 7-14 days when PBMCs were
      cultured from healthy goats free from SRLV infection. These MGCs expressed
      tartrate-resistant acid phosphatase, calcitonin receptor, integrin alphaVbeta3,
      cathepsin K and matrix metalloproteinase 9 and were able to resorb bone in vitro
      in the absence of RANKL and macrophage colony stimulating factor, consistent with
      an osteoclast phenotype.

PMID- 20822939
TI  - Brain-natriuretic peptide and cyclic guanosine monophosphate as biomarkers of
      myxomatous mitral valve disease in dogs.
AB  - Elevations in the plasma concentrations of natriuretic peptides correlate with
      increased severity of myxomatous mitral valve disease (MMVD) in dogs. This study
      correlates the severity of MMVD with the plasma concentrations of the biomarkers
      N-terminal fragment of the pro-brain-natriuretic peptide (NT-proBNP) and its
      second messenger, cyclic guanosine monophosphate (cGMP). Furthermore, the L
      arginine:asymmetric dimethylarginine (ADMA) ratio was measured as an index of
      nitric oxide availability. The study included 75 dogs sub-divided into five
      groups based on severity of MMVD as assessed by clinical examination and
      echocardiography. Plasma NT-proBNP and cGMP concentrations increased with
      increasing valve dysfunction and were significantly elevated in dogs with heart
      failure. The cGMP:NT-proBNP ratio decreased significantly in dogs with heart
      failure, suggesting the development of natriuretic peptide resistance. Although
      the l-arginine:ADMA ratio decreased with increasingly severe MMVD, this was
      largely due to the older age of the dogs with heart failure.

PMID- 20822940
TI  - Molecular and virulence characteristics of multi-drug resistant Salmonella
      Enteritidis strains isolated from poultry.
AB  - Forty-six Salmonella enterica subspecies enterica serovar Enteritidis (S.
      Enteritidis) strains were isolated from chicken meat, faeces, and eggshells
      collected from hatcheries throughout Korea. The strains were examined for the
      presence of antimicrobial resistance and virulence genes. All 46 isolates were
      resistant to at least one of 21 antibiotics used in this study, 30 (65.2%) were
      resistant to three or more antimicrobials, and a single remarkable isolate was
      resistant to 15 antimicrobials. The isolates were primarily resistant to
      penicillins, sulfisoxazole, streptomycin, tetracycline and quinolones. The high
      rate of resistance in S. Enteritidis strains, sometimes to multiple drugs, may
      complicate future options for treating human infections. Nineteen of the 21
      penicillin resistant isolates carried the bla(TEM) gene, while one strain,
      resistant both to penicillins and ceftriaxone, carried the bla(CTX-M) gene.
      Thirty-seven of the 45 sulfisoxazole resistant isolates carried sul2, and 23/24
      streptomycin resistant isolates carried both strA and strB. All 10 tetracycline
      resistant isolates carried the tet(A) gene. Most isolates harboured both SPI-1
      and SPI-2-associated genes, and the spv operon, which are known to be associated
      with human infections. The presence of these genes suggests that these strains
      could give rise to public health problems if dispersed in the general human
      population.

PMID- 20822941
TI  - Which variables are associated with pain intensity and treatment response in
      advanced cancer patients?--Implications for a future classification system for
      cancer pain.
AB  - BACKGROUND: This study is part of a research program to reach consensus on an
      international cancer pain classification system. A confirmative and explorative
      approach was applied to investigate which of the variables identified in the
      literature, by experts and patients that are associated with pain. METHODS: Data
      from an international, multicentre, cross-sectional study of cancer patients
      treated with opioids were investigated. Dependent variables were: average pain,
      worst pain, and pain relief (11-point Numerical Rating Scales). Forty-six
      independent variables were chosen based upon previous studies. Bivariate analyses
      identified independent variables associated with at least one of the dependent
      ones; 21 were included in multivariate linear regression analyses. RESULTS: Two
      thousand two hundred and seventy-eight patients were investigated; 52% males,
      mean age 62 years, mean Karnofsky Performance Status 59%, mean daily opioid oral
      equivalent dose 341 mg. Fifty-eight percent had breakthrough pain. Mean pain
      scores were: average pain 3.5, worst pain 5.3 and pain relief 74%. Variables most
      strongly associated with these three dependent variables were: breakthrough pain,
      psychological distress, sleep, and opioid dose. CONCLUSIONS: Breakthrough pain
      and psychological distress were confirmed as key variables of a future
      classification system. Candidate variables were: sleep, opioid dose, pain
      mechanism, use of non-opioids, pain localisation, cancer diagnosis, location of
      metastases, and addiction.

PMID- 20822943
TI  - Design and characterization of a calixarene inclusion compound for calibration of
      long-range carbon-fluorine distance measurements by solid-state NMR.
AB  - An inexpensive, easily synthesized calixarene:fluorotoluene host:guest inclusion
      complex has been designed for optimization and calibration of solid-state NMR
      measurements of carbon-fluorine distances using Rotational Echo DOuble Resonance
      (REDOR). Complexation of the fluorotoluene with the calixarene host separates the
      molecules such that simple two-spin behavior is observed for one site with a 4.08
      A carbon-fluorine distance. Fluorotoluene dynamics within the calixarene matrix
      cause motional averaging of the dipolar couplings, which makes it possible to
      easily optimize REDOR experiments and test their accuracy for relatively long
      distance measurements (>6.6 A). This provides a new tool for accurate REDOR
      measurements of long carbon-fluorine distances, which have important applications
      in the characterization of fluorine-containing drugs, proteins, and polymers.

PMID- 20822942
TI  - Clinical effects and brain metabolic correlates in non-invasive cortical
      neuromodulation for visceral pain.
AB  - BACKGROUND AND AIMS: Chronic visceral pain is frequent, extremely debilitating,
      and generally resistant to pharmacological treatment. It has been shown that
      chronic visceral inflammation, through altered afferent visceral sensory input,
      leads to plastic changes in the central nervous system that ultimately sustain
      pain. Therefore approaches aiming at modulation of brain activity are attractive
      candidates to control visceral pain. METHODS: Here we report findings of a phase
      II, sham-controlled clinical trial assessing the clinical effects and brain
      metabolic correlates of a 10-day course of daily sessions of slow-frequency,
      repetitive transcranial magnetic stimulation (rTMS) targeting the right secondary
      somatosensory cortex (SII) in patients with chronic pancreatitis and severe
      visceral pain. RESULTS: Our results show a significant reduction in pain after
      real rTMS that lasted for at least 3 weeks following treatment. These clinical
      changes were correlated with increases in glutamate and N-acetyl aspartate (NAA)
      levels--neurometabolites associated with cortical activity and brain damage--as
      measured by in vivo single-voxel proton magnetic resonance spectroscopy (1H-MRS).
      Adverse effects in the real rTMS group were mild and short-lasting. CONCLUSIONS:
      Our results support preliminary findings showing that modulation of right SII
      with rTMS is associated with a significant analgesic effect and that this effect
      is correlated with an increase in excitatory neurotransmitter levels such as
      glutamate and NAA.

PMID- 20822944
TI  - Clinical comparison of primary versus secondary epilepsy in 125 cats.
AB  - In the present study 125 cats with recurrent seizures were analysed. The main
      goal was to investigate the aetiology and compare primary epilepsy (PE) with
      secondary epilepsy (SE) regarding signalment, history, ictal pattern, clinical
      and neurological findings. Seizure aetiology was classified as PE in 47 (38%) and
      SE in 78 (62%) cats. SE was caused mainly by intracranial neoplasia (16),
      hippocampal necrosis (14), toxicosis (eight), and encephalitis (seven). A
      significant difference between PE and SE was found in: age, body weight, duration
      of seizure, occurrence of status epilepticus and neurological deficits. Status
      epilepticus, altered interictal neurological status and seizure onset over the
      age of 7 years indicated SE more frequently than PE. If the seizures occurred
      during resting conditions and rapid running occurred the aetiology was more
      likely to be PE than SE.

PMID- 20822945
TI  - Incidental findings in post-mortem CT: Calcified ligamentum arteriosum.
AB  - This case report describes the incidental finding of a calcified ligamentum
      arteriosum during post-mortem CT examination. The calcification of the ligament
      was confirmed at autopsy. Subsequent histological examination revealed the
      presence of cartilage-like and bone-like tissue as well as extended calcification
      areas. The importance of not confusing this normal post-mortem CT finding with
      vessel pathology is being emphasized.

PMID- 20822947
TI  - Enzyme dynamics point to stepwise conformational selection in catalysis.
AB  - Recent data increasingly reveal that conformational dynamics are indispensable to
      enzyme function throughout the catalytic cycle, in substrate recruiting, chemical
      transformation, and product release. Conformational transitions may involve
      conformational selection and induced fit, which can be viewed as a special case
      in the catalytic network. NMR, X-ray crystallography, single-molecule FRET, and
      simulations clearly demonstrate that the free enzyme dynamics already encompass
      all the conformations necessary for substrate binding, preorganization,
      transition-state stabilization, and product release. Conformational selection and
      substate population shift at each step of the catalytic turnover can accommodate
      enzyme specificity and efficiency. Within such a framework, entropy can have a
      larger role in conformational dynamics than in direct energy transfer in
      dynamically promoted catalysis.

PMID- 20822946
TI  - Choreographing an enzyme's dance.
AB  - While ground state structures combined with chemical tools and enzyme kinetics
      deliver useful information on possible chemical mechanisms of enzyme catalysis,
      they do not unravel the finely balanced energy inventory to explain the
      impressive rate enhancement of enzymes. For this goal, a complete description of
      enzyme catalysis in the form of an energy landscape is needed. Since the rate of
      catalysis is determined by the climb over a sequence of energy barriers, we focus
      here on the critical question of transition pathways. A combination of time
      resolved NMR and simulation deliver a glimpse into how proteins can so
      efficiently move within the ensemble of the native conformations while avoiding
      unfolding during that journey. The loss of energy due to breakage of native
      contacts is compensated by non-native transient hydrogen bonds during the
      transition thereby 'holding on' to the energy until the new native contacts form
      that define the alternate functional state. The use of kinetic isotope effects
      (KIE) to study the chemical step show that coordinated atomic fluctuations of the
      protein component dictate the probability of 'correct' distance and orientation,
      due to its extreme sensitivity to distance. The examples here stress the point
      that highly choreographed conformational sampling together with chemical
      integrity is a prerequisite for efficient enzyme catalysis.

PMID- 20822948
TI  - Regulated trafficking of cellulose synthases.
AB  - New findings reveal that proteins involved in cellulose biosynthesis undergo
      regulated trafficking between intracellular compartments and the plasma membrane.
      The coordinated secretion and internalization of these proteins involve both the
      actin and cortical microtubule cytoskeletons. This regulated trafficking allows
      the dynamic remodeling of cellulose synthase complex (CSC) secretion during cell
      expansion and differentiation. Several new actors of the cellulose synthesis
      machinery have been recently identified.

PMID- 20822949
TI  - Spectroscopic and theoretical study on the interaction between diperoxovanadate
      complexes and glycyl-histidine.
AB  - The interaction between diperoxovanadate complexes (K3)[VO(O2)2(C2O4)].H2O and
      [VO(O2)2(D2O)](-)/[VO(O2)2(HOD)](-)) and glycyl-histidine (abbr. GlyHis) in
      solution was studied by 1D NMR including variable-temperature NMR, 2D diffusion
      ordered spectroscopy (DOSY), HMQC and density functional theory (DFT)
      calculations. The results indicate that a pair of [VO(O2)2(GlyHis)](-) isomers is
      formed. The vanadium in the new species is coordinated by either the E-N or delta
      N in the imidazole ring. The relative ratio of the isomers was affected by
      temperature. Theoretical calculation results provide a reasonable explanation on
      the relative coordination capability of different nitrogen sites. Solvation
      effect is shown to be important for the reactivity of the interaction system.

PMID- 20822950
TI  - Homogeneous competitive assay of ligand affinities based on quenching
      fluorescence of tyrosine/tryptophan residues in a protein via Forster-resonance
      energy-transfer.
AB  - A new homogeneous competitive assay of ligand affinities was proposed based on
      quenching the fluorescence of tryptophan/tyrosine residues in a protein via
      Forster-resonance-energy-transfer using a fluorescent reference ligand as the
      acceptor. Under excitation around 280 nm, the fluorescence of a protein or a
      bound acceptor was monitored upon competitive binding against a nonfluorescent
      candidate ligand. Chemometrics for deriving the binding ratio of the acceptor
      with either fluorescence signal was discussed; the dissociation constant (K(d))
      of a nonfluorescent candidate ligand was calculated from its concentration to
      displace 50% binding of the acceptor. N-biotinyl-N'-(1-naphthyl)-ethylenediamine
      (BNEDA) and N-biotinyl-N'-dansyl-ethylenediamine (BDEDA) were used as the
      reference ligands and acceptors to streptavidin to test this new homogeneous
      competitive assay. Upon binding of an acceptor to streptavidin, there were the
      quench of streptavidin fluorescence at 340 nm and the characteristic fluorescence
      at 430 nm for BNEDA or at 525 nm for BDEDA. K(d) of BNEDA and BDEDA was obtained
      via competitive binding against biotin. By quantifying BNEDA fluorescence, K(d)
      of each tested nonfluorescent biotin derivative was consistent with that by
      quantifying streptavidin fluorescence using BNEDA or BDEDA as the acceptor. The
      overall coefficients of variation were about 10%. Therefore, this homogeneous
      competitive assay was effective and promising to high-throughput-screening.

PMID- 20822951
TI  - Point-to-point projection from muscle afferent to area 4 cortex.

PMID- 20822953
TI  - Does the motor cortex influence denervation in ALS? EMG studies of muscles with
      both contralateral and bilateral corticospinal innervation.
AB  - OBJECTIVES: To evaluate the pattern of degeneration of lower motor neuron
      progression in ALS in relation to the contralateral and ipsilateral corticospinal
      innervation of the tested muscles. METHODS: EMG evaluation of the sternomastoid
      and trapezius muscles on one or both sides, and transcranial magnetic stimulation
      to record motor evoked responses from these muscles after ipsilateral and
      contralateral cortical stimulation. The sternomastoid muscle receives
      corticospinal input from both hemispheres, but the trapezius only a contralateral
      corticospinal innervation; however the power motor innervation of both these
      muscles is derived from the same spinal nucleus, and the same motor nerve.
      Seventy-five patients with ALS were studied at the time of diagnosis, and 54
      control subjects, consisting of normal subjects and disease control subjects. MUP
      analysis and spontaneous activity were assessed. RESULTS: We confirmed that the
      sternomastoid receives both contralateral and ipsilateral corticospinal
      innervation, and the trapezius usually only contralateral innervation. The MUP
      analysis revealed symmetric changes in sternomastoid and trapezius muscles, and
      both muscles were equally affected. CONCLUSIONS: Our findings are in accord with
      the concept that LMN degeneration in ALS is related to local factors in the
      spinal cord. SIGNIFICANCE: Our findings suggest that local factors in the spinal
      grey matter are important in causing LMN degeneration in ALS, but they do not
      rule out a corticomotoneuronal contribution.

PMID- 20822952
TI  - Auditory cortical N100 in pre- and post-synaptic auditory neuropathy to frequency
      or intensity changes of continuous tones.
AB  - OBJECTIVES: Auditory cortical N100s were examined in ten auditory neuropathy (AN)
      subjects as objective measures of impaired hearing. METHODS: Latencies and
      amplitudes of N100 in AN to increases of frequency (4-50%) or intensity (4-8 dB)
      of low (250 Hz) or high (4000 Hz) frequency tones were compared with results from
      normal-hearing controls. The sites of auditory nerve dysfunction were pre
      synaptic (n=3) due to otoferlin mutations causing temperature sensitive deafness,
      post-synaptic (n=4) affecting other cranial and/or peripheral neuropathies, and
      undefined (n=3). RESULTS: AN consistently had N100s only to the largest changes
      of frequency or intensity whereas controls consistently had N100s to all but the
      smallest frequency and intensity changes. N100 latency in AN was significantly
      delayed compared to controls, more so for 250 than for 4000 Hz and more so for
      changes of intensity compared to frequency. N100 amplitudes to frequency change
      were significantly reduced in ANs compared to controls, except for pre-synaptic
      AN in whom amplitudes were greater than controls. N100 latency to frequency
      change of 250 but not of 4000 Hz was significantly related to speech perception
      scores. CONCLUSIONS: As a group, AN subjects' N100 potentials were abnormally
      delayed and smaller, particularly for low frequency. The extent of these
      abnormalities differed between pre- and post-synaptic forms of the disorder.
      SIGNIFICANCE: Abnormalities of auditory cortical N100 in AN reflect disorders of
      both temporal processing (low frequency) and neural adaptation (high frequency).
      Auditory N100 latency to the low frequency provides an objective measure of the
      degree of impaired speech perception in AN.

PMID- 20822954
TI  - CA125--a test with a change of heart.
AB  - CA125 is well known as a tumour marker for ovarian cancer. Like all tumour
      markers it is not specific for a specific tumour and may be elevated in benign
      disease. Even in ovarian cancer it seems that CA125 is derived from mesothelial
      production rather than from the cancer cells. CA125 is a natural product of
      serosal epithelial cells and present in most serosal fluids whether malignant or
      benign. Benign causes of CA125 elevation include liver cirrhosis, peritoneal
      infection, abdominal surgery or the congestion of cardiac failure. Elevated CA125
      levels are found in ascitic, pleural or pericardial fluid of patients with
      cardiac failure and the serum levels correlate with the clinical staging of
      cardiac failure. Whilst CA125 levels might be useful for diagnosis of cardiac
      failure, it has an equally impressive ability for defining prognosis in that
      condition, especially when combined with measuring natriuretic peptides. The
      CA125 assay is not standardised and different methods, such as new CA125II
      assays, often give differing results. Furthermore, as CA125 levels fall at the
      menopause, and may rise in the elderly, reference limits appropriate for age and
      gender need to be refined in order for CA125 to fulfil any of its potential as a
      marker of cardiac failure in these age groups.

PMID- 20822956
TI  - Expectations and voluntary attrition in nursing students.
AB  - This paper presents a series of findings generated during a larger study which
      aimed to develop a theoretical understanding of the reasons why nursing students
      voluntarily leave pre-registration nursing programmes. In this study, significant
      incongruence was found to exist between student expectations of pre-registration
      nursing programmes and the reality of these programmes following entry. The
      resulting dissonance was identified as an important factor in student decisions
      to voluntarily withdraw. A single case study design was selected to explore the
      causes of voluntary attrition in nursing students within a School of Nursing and
      Midwifery. The study population was obtained through purposeful sampling and
      consisted of 15 students who had previously voluntarily withdrawn from pre
      registration nursing programmes. A semi-structured interview method was used to
      collect data from study participants. The interview schedule developed for use in
      the study reflected the key components of the conceptual model of higher
      education (HE) student attrition (Tinto, 1975, 1987, 1993). All interviews were
      tape recorded to facilitate later transcription. The Cyclical or Interactive
      Model of Qualitative Research (Miles and Huberman, 1994) was used to analyse data
      collected from study participants. This paper describes the unrealistic range of
      expectations which nursing students have of nursing, the information sources and
      experiences which inform student expectations and how ambiguous expectations
      contributed to voluntarily attrition.

PMID- 20822955
TI  - SnoN in mammalian development, function and diseases.
AB  - SnoN (Ski-novel protein) was discovered as a nuclear proto-oncogene on the basis
      of its ability to induce transformation of chicken and quail embryonic
      fibroblasts. As a crucial negative regulator of transforming growth factor-beta
      (TGF-beta) signaling and also an activator of p53, it plays an important role in
      regulating cell proliferation, senescence, apoptosis, and differentiation. Recent
      studies of its expression patterns and functions in mouse models and mammalian
      cells have revealed important functions of SnoN in normal epithelial development
      and tumorigenesis. Evidence suggests that SnoN has both pro-oncogenic and anti
      oncogenic functions by modulating multiple signaling pathways. These studies
      suggest that SnoN may have broad functions in the development and homeostasis of
      embryonic and postnatal tissues.

PMID- 20822957
TI  - Fertility preservation for breast-cancer patients using IVM followed by oocyte or
      embryo vitrification.
AB  - Unstimulated in-vitro maturation (IVM) cycles are considered for fertility
      preservation in breast cancer due to avoidance of ovarian stimulation and
      shortened time to oocyte retrieval. This study evaluated the efficacy of this
      approach in a retrospective cohort analysis of 66 patients with breast cancer.
      Immature oocytes were collected and matured in vitro and then either vitrified or
      fertilized and preserved as vitrified embryos. In group 1 (vitrified oocytes,
      n=35), the average number of oocytes retrieved was 11.4 +/- 8.8, the maturation
      rate was 64.2% and an average of 7.9 +/- 6.6 oocytes were vitrified per patient
      treated. The median duration from the first evaluation to oocyte retrieval was 8
      days. In group 2 (vitrified embryos, n=31) the average number of oocytes
      retrieved was 9.7 +/- 6.4, the maturation rate was 53.2% and an average of 5.8 +/
      2.7 mature oocytes were available for fertilization/patient. The fertilization
      rate was 77.8%, resulting in 4.5 +/- 2.7 vitrified embryos/patient. The median
      duration from the first evaluation to oocyte retrieval was 13 days. Calculated
      pregnancy rates per vitrified oocyte and embryo were 3.8% and 8.1%, respectively.
      IVM can be considered a useful option for fertility preservation in breast-cancer
      patients.

PMID- 20822958
TI  - Tuberculous meningitis: a uniform case definition for use in clinical research.
AB  - Tuberculous meningitis causes substantial mortality and morbidity in children and
      adults. More research is urgently needed to better understand the pathogenesis of
      disease and to improve its clinical management and outcome. A major stumbling
      block is the absence of standardised diagnostic criteria. The different case
      definitions used in various studies makes comparison of research findings
      difficult, prevents the best use of existing data, and limits the management of
      disease. To address this problem, a 3-day tuberculous meningitis workshop took
      place in Cape Town, South Africa, and was attended by 41 international
      participants experienced in the research or management of tuberculous meningitis.
      During the meeting, diagnostic criteria were assessed and discussed, after which
      a writing committee was appointed to finalise a consensus case definition for
      tuberculous meningitis for use in future clinical research. We present the
      consensus case definition together with the rationale behind the recommendations.
      This case definition is applicable irrespective of the patient's age, HIV
      infection status, or the resources available in the research setting. Consistent
      use of the proposed case definition will aid comparison of studies, improve
      scientific communication, and ultimately improve care.

PMID- 20822959
TI  - Biomarkers of immunoregulatory status in stable liver transplant recipients
      undergoing weaning of immunosuppressive therapy.
AB  - Biomarkers that reflect immune response recovery and predict clinical events
      during withdrawal or minimization of immunosuppressive therapy have not been
      evaluated. This study aimed to evaluate whether immune response recovers after
      withdrawal of long-term immunosuppressive treatment in stable liver transplant
      patients and to determine whether specific biomarkers reflect immune response
      reactivity and predict rejection. Pharmacokinetic-pharmacodynamic profiles were
      determined in 24 patients and 80 healthy donors before immunosuppressive
      treatment reduction began, at 50%, and at complete withdrawal. In patients who
      rejected, effector-T-cell response mediated by soluble IFN-gamma, %CD4(+)IFN
      gamma and %CD8(+)IL-2/IFN-gamma were significantly increased, while TGF-beta1
      production and the TGF-beta1/IFN-gamma ratio were significantly decreased. In
      patients with rejection, soluble IFN-gamma and %CD8(+)IL-2 were significantly
      higher before immunosuppressive treatment was reduced. Further studies are
      required, but this battery of biomarkers performed in whole blood could be a
      useful tool to monitor immunosuppressive treatment minimization or withdrawal
      protocols and identify patients at increased risk of rejection.

PMID- 20822960
TI  - A distinct subset of HLA-DR+-regulatory T cells is involved in the induction of
      preterm labor during pregnancy and in the induction of organ rejection after
      transplantation.
AB  - Regulatory T cells (Tregs) are known to suppress alloimmune responses during
      pregnancy and post organ transplantation. We demonstrate that a distinct subset
      of FoxP3(+)DR(+)-Tregs among the total CD4(+)CD127(low+/-)CD25(+)-Treg cell pool
      is critically involved in preterm labor induction and kidney transplant rejection
      as well. Compared to healthy pregnancies and non-rejecting kidney recipients, we
      found that the percentage of the FoxP3(+)DR(+)-Treg subset was not reduced, but
      that the level of HLA-DR expression of such Tregs was strongly diminished in
      preterm laboring women and in patients with acute renal allograft rejection. In
      addition, both patient collectives showed a significantly reduced suppressive
      activity of their circulating CD4(+)CD127(low+/-)CD25(+)-Treg cell pool. Our
      findings propose that the FoxP3(+)DR(+)-Treg subset may be decisively responsible
      for the suppressive activity of the total CD4(+)CD127(low+/-)CD25(+)-Treg cell
      pool and that the immunologic mechanisms leading to preterm labor necessitating
      preterm delivery may be similar to those leading to allograft rejection after
      transplantation.

PMID- 20822961
TI  - Commissioning abortion and sexual health services.
AB  - This guidance offers best practice advice for commissioning termination of
      pregnancy services. It presents relevant publications including Department of
      Health guidance in connection with the key requirements for service provision.
      Commissioners are encouraged to examine their existing care pathways and
      contracted services to ensure that women are offered an equitable, appropriate
      and holistic service, which can be accessed as quickly as possible. The
      importance of associated services such as contraception and sexual health
      screening is explained. The National Service Specification for Termination of
      Pregnancy Services is examined in depth and key suggestions for compliance are
      supplied. This includes an outline of the benefits of extending the choice of
      service providers in conjunction with the implementation of self-referral and
      central booking services.

PMID- 20822963
TI  - CT evaluation of torsional malalignment after intertrochanteric fracture
      fixation.
AB  - INTRODUCTION: Trochanteric fractures are commonly stabilized either by
      intramedullary nailing or plate and screw fixation after reduction on the
      orthopaedic surgical table under radiological guidance. HYPOTHESIS: Closed
      trochanteric fracture anatomic reduction is difficult in the transversal plane.
      OBJECTIVES: The objective of this prospective study was to assess the rotational
      malalignment induced after reduction and osteosynthesis of trochanteric
      fractures. PATIENTS AND METHODS: Prospective study including 40 patients (mean
      age, 78 years; range, 51-90 years) operated for a trochanteric fracture between
      January 2007 and September 2008. Fourteen fractures were treated using DHSTM
      (SynthesTM) plate and screw fixation and 26 with intramedullary nailing
      (trochanteric nailTM, StrykerTM). All these patients underwent postoperative CT
      of the pelvis during their hospitalization with measurement of anteversion of the
      operated and healthy femoral necks at the posterior condyles. The evaluation
      criterion was whether or not there was malalignment greater than 15 degrees  on
      the operated side compared to the healthy side. RESULTS: The mean anteversion was
      14.2 degrees  for the healthy side and 23 degrees  for the operated side. The
      mean rotational malalignment was 15.3 degrees . Forty percent of the rotational
      malalignments were greater than 15 degrees , with a majority of cases showing
      excess internal rotation (35%) of the distal fragment. CONCLUSION AND DISCUSSION:
      The rate of internal rotational malalignment of the distal fragment greater than
      15 degrees  was high (40% of this series). This should encourage surgeons to
      reduce the excess internal rotation that tends to be attributed to the distal
      fragment during preoperative reduction of these fractures. LEVEL OF EVIDENCE:
      Level III. Prospective diagnostic study with no control group.

PMID- 20822964
TI  - Does cancer in a child affect parents' employment and earnings? A population
      based study.
AB  - PURPOSE: Cancer in a child may adversely affect parents' work opportunities due
      to enlarged care burdens and/or altered priorities. Few studies exist, and
      possible effects on parental employment and earnings were therefore explored.
      MATERIALS AND METHODS: Data on the entire Norwegian population aged 27-65 with
      children under the age of 20 in 1990-2002 (N=1.2 million) was retrieved from
      national registries. Employment rates for parents of 3263 children with cancer
      were compared to those of parents with children without cancer by means of
      logistic regression models. Log-linear regression models were used to explore
      childhood cancer's effect on parental earnings for the large majority of parents
      who remained employed. RESULTS: Cancer in a child was in general not associated
      with a reduced risk of employment, although some exceptions exist among both
      mothers and fathers. For employed mothers, CNS cancers, germinal cell cancers,
      and unspecified leukemia were associated with significant reductions in earnings
      (10%, 21%, and 60%, respectively). Reductions were particularly pronounced for
      mothers with a young and alive child, and became more pronounced with time
      elapsed from diagnosis. Fathers' earnings were not affected significantly.
      DISCUSSION AND CONCLUSION: Parents' employment is not adversely affected by a
      child's cancer in Norway. Earnings are reduced in certain instances, but the
      overall effects are minor. Generous welfare options and flexible labor markets
      typical for Nordic welfare states may account for this. In line with traditional
      caregiving responsibilities, reductions in earnings were most pronounced for
      mothers.

PMID- 20822965
TI  - Management of major vascular complications of laparoscopic surgery.

PMID- 20822966
TI  - Cryptoglandular anal fistula.
AB  - Fistula arising from the glands of the anal crypts is the most common form of
      anoperineal sepsis. It is characterized by a primary internal orifice in the anal
      canal, a fistulous tract, and an abscess and/or secondary perineal orifice with
      purulent discharge. Antibiotics are not curative. The treatment of an abscess is
      urgent and consists, whenever possible, of incision and drainage under local
      anesthesia. Definitive treatment of the fistulous tract can await a second stage.
      The primary aim is to control infection without sacrificing anal continence.
      Fistulotomy is the basis for all treatments but the specific technique depends on
      the height of the fistula in relation to the sphincteric mechanism. Overall
      results of fistulotomy are excellent but there is some risk of anal incontinence.
      This explains the growing interest in sphincter sparing techniques such as the
      mucosal advancement flap, the injection of fibrin glue, and the plug procedure.
      However, results of these procedures are not yet good enough and leave much room
      for improvement.

PMID- 20822968
TI  - Vascular effects of ultrafine particles in persons with type 2 diabetes.
AB  - BACKGROUND: Diabetes confers an increased risk for cardiovascular effects of
      airborne particles. OBJECTIVE: We hypothesized that inhalation of elemental
      carbon ultrafine particles (UFP) would activate blood platelets and vascular
      endothelium in people with type 2 diabetes. METHODS: In a randomized, double
      blind, crossover trial, 19 subjects with type 2 diabetes inhaled filtered air or
      50 ug/m3 elemental carbon UFP (count median diameter, 32 nm) by mouthpiece for 2
      hr at rest. We repeatedly measured markers of vascular activation, coagulation,
      and systemic inflammation before and after exposure. RESULTS: Compared with air,
      particle exposure increased platelet expression of CD40 ligand (CD40L) and the
      number of platelet-leukocyte conjugates 3.5 hr after exposure. Soluble CD40L
      decreased with UFP exposure. Plasma von Willebrand factor increased immediately
      after exposure. There were no effects of particles on plasma tissue factor,
      coagulation factors VII or IX, or D-dimer. CONCLUSIONS: Inhalation of elemental
      carbon UFP for 2-hr transiently activated platelets, and possibly the vascular
      endothelium, in people with type 2 diabetes.

PMID- 20822969
TI  - The influence of dietary patterns on acne vulgaris in Koreans.
AB  - The association between acne and food has been evaluated with inconsistent
      results. We enrolled 783 patients with acne and 502 control subjects. For the
      patients with acne, blood tests for insulin, insulin-like growth factor-1 (IGF
      1), insulin-like growth factor binding protein-3 (IGFBP-3), post prandial 2 hours
      blood glucose (PP2), and dehydroepiandrosterone sulphate (DHEAS) were performed.
      The acne patients were divided into an "aggravated by food" group (AF) and a "not
      aggravated by food" group (NAF). All participants were asked to fill out a
      questionnaire. The frequency of vegetables (yellow, green leafy, cruciferous) (P
      = .001) and fish (white flesh and green fish, blue tuna) ((P = .03) intake was
      significantly higher in the control group than in the acne group. Intake of
      instant noodles (P = .01), junk food (P = .002), carbonated drinks (P = .005),
      snacks (P = .001), processed cheeses (P = .04), pork (braised) (P = .02), pork
      (roast) (P < .001), chicken (fried) (P = .001), chicken (stewed) (P = .001), nuts
      (P = .002) and seaweed (P = .003) were significantly higher in the acne patients
      than in the controls. Intake of roast pork (P = .02), fried chicken (P < .02),
      and nuts (P = .03) was significantly higher in the AF than NAF. In addition, the
      regularity of inter-meal intervals (P < .001) and breakfast intake (P < .001)
      were significantly lower in the acne patients. IGF-1 and IGFBP-3 showed sexual
      differences. This study also showed that a high glycemic load diet, dairy food
      intake, high fat diet, and iodine in Korean foods appear to play a role in acne
      exacerbation. In addition, irregular dietary patterns were found to aggravate
      acne.

PMID- 20822970
TI  - The evolution and use of skin explants: potential and limitations for
      dermatological research.
AB  - Different models have been developed to understand the biology of skin or to test
      pharmaceutical/cosmetic products. These models can be in vitro models that
      possess advantages such as mono and co-culture models in 2D, which are very
      reproducible, or organotypic models (skin explant and reconstructed skin) that
      present a 3D organisation. Animal or human in vivo models allow studies that are
      closer to reality. In virtuo models developed on computers control all known
      parameters and do not require animals. The major limitations of these models are
      the lack of 3D structure for in vitro culture, the variability of results from
      organotypic models, ethical problems inherent to human and animal tests and the
      presence of numerous unknown parameters in in virtuo systems. Despite their
      limitations, skin explants seem to be an interesting model for studies. Skin
      explants may be kept from a few hours to 10-14 days on supports or directly in
      culture medium. These explants are generally cultivated at 37  degrees C, 5%
      CO(2), preferentially in serum-free conditions. Three basic techniques are used
      to characterise these models: histological stains, proliferation, apoptosis and
      cytotoxicity tests. Skin explants could be a very convenient model to study wound
      healing, inflammation processes, autoimmune diseases, malignant transformation,
      stress, ageing, and to serve as screening tests.

PMID- 20822971
TI  - A comparative study of allergic contact dermatitis by patch test versus
      reflectance confocal laser microscopy, with nickel and cobalt.
AB  - Few studies have reported on the accuracy of reflectance confocal laser
      microscopy (RCLM) in observing allergic contact dermatitis in vivo. However,
      distinction of skin reactions from different reagents is not well understood. We
      sought to diagnose allergic contact dermatitis by RCLM images and compare with
      routine, visual patch test (PT) reading for 2 major allergen metals in Japan. The
      PT was performed on the upper back skin with 5% nickel sulfate (Ni) and 2% cobalt
      chloride (Co) in eight healthy volunteers and eleven patients. RCLM was used to
      calculate the thickness of the suprabasal epidermis after visual assessment of
      PT. Comparison of clinical scoring versus suprabasal epidermal thickness was
      observed. RCLM images of positive PT showed increased suprabasal epidermal
      thickness on day 2 (D2), and D3 for Co, whereas there was vesicle formation and
      an overall increase suprabasal epidermal thickness for Ni. In two of 3 doubtful
      positive PT to Co, RCLM images presented characteristics of irritant reactions;
      and one characteristic of a positive reaction. The frequency of Co doubtful
      positive PT was higher than that of Ni. We found advantages in using RCLM for
      visualizing features of allergic contact dermatitis and found it a useful tool as
      an objective parameter in grading severity and types of PT reaction.

PMID- 20822972
TI  - Buruli ulcer caused by "Mycobacterium ulcerans subsp. shinshuense".

PMID- 20822973
TI  - Multiple pilosebaceous cysts induced by topical steroid therapy.

PMID- 20822974
TI  - Annular atrophic lichen planus.

PMID- 20822975
TI  - Benign infantile focal epilepsy with midline spikes and waves during sleep: a new
      epileptic syndrome or a variant of benign focal epilepsy?
AB  - OBJECTIVE: To analyze the electroclinical features and evolution of seven infants
      with benign infantile focal epilepsy with midline spikes and waves during sleep
      (BIMSE). MATERIAL AND METHODS: Seven patients were examined at our department
      between February 2003 and February 2009, with onset of seizures between six and
      13 months of age (mean, 10.2 months; median, 11 months). Patients with
      cryptogenic and symptomatic focal epilepsies were excluded. Sex, age, familial
      history, type of seizures and AED treatment were noted and EEG monitoring, MRI
      and CT scanning, and developmental and psychomotor evolution were investigated.
      RESULTS: Patients included five males and two females. All patients suffered from
      seizures during wakefulness. Two of the patients (29%) did not have a recurrence.
      Five (71%) had sporadic seizures (ranging between two and five). One of the seven
      patients (14%) presented with seizures in clusters. During seizures, staring was
      observed in six (86%), motion arrest in five (71%), stiffening in five (71%),
      cyanosis in three (42%), automatisms in one (14%) and lateralizing signs in four
      (57%). Two patients (29%) had secondary generalisation. The duration of the
      seizures ranged between 30 seconds and five minutes. No status epilepticus was
      observed. The interictal EEG recording during sleep showed low-voltage unilateral
      or bilateral spikes located in the central and vertex regions, followed by slow
      waves in all patients. Outcome was excellent in all patients. CONCLUSION: We
      believe that BIMSE is a new syndrome rather than an early presentation of benign
      epilepsy of childhood with centrotemporal spikes, Panayiotopoulos syndrome, or a
      late presentation of benign focal infantile seizures.

PMID- 20822980
TI  - Wind-instruments lung: a foul note.

PMID- 20822981
TI  - Tobacco smoke, malignancies, and history.

PMID- 20822982
TI  - The clustering of disorders related to childhood sleep-disordered breathing: are
      they related to a single mechanism?

PMID- 20822983
TI  - Exhaled breath condensate: delusion or dilution?

PMID- 20822984
TI  - "Meaningful use" means process redesign.

PMID- 20822986
TI  - Point: adherence to early goal-directed therapy: does it really matter? Yes.
      After a decade, the scientific proof speaks for itself.

PMID- 20822987
TI  - Counterpoint: adherence to early goal-directed therapy: does it really matter?
      No. Both risks and benefits require further study.

PMID- 20822990
TI  - Exhaled nitric oxide in pulmonary diseases: a comprehensive review.
AB  - The upregulation of nitric oxide (NO) by inflammatory cytokines and mediators in
      central and peripheral airway sites can be monitored easily in exhaled air. It is
      now possible to estimate the predominant site of increased fraction of exhaled NO
      (FeNO) and its potential pathologic and physiologic role in various pulmonary
      diseases. In asthma, increased FeNO reflects eosinophilic-mediated inflammatory
      pathways moderately well in central and/or peripheral airway sites and implies
      increased inhaled and systemic corticosteroid responsiveness. Recently, five
      randomized controlled algorithm asthma trials reported only equivocal benefits of
      adding measurements of FeNO to usual clinical guideline management including
      spirometry; however, significant design issues may exist. Overall, FeNO
      measurement at a single expiratory flow rate of 50 mL/s may be an important
      adjunct for diagnosis and management in selected cases of asthma. This may
      supplement standard clinical asthma care guidelines, including spirometry,
      providing a noninvasive window into predominantly large-airway-presumed
      eosinophilic inflammation. In COPD, large/central airway maximal NO flux and
      peripheral/small airway/alveolar NO concentration may be normal and the role of
      FeNO monitoring is less clear and therefore less established than in asthma.
      Furthermore, concurrent smoking reduces FeNO. Monitoring FeNO in pulmonary
      hypertension and cystic fibrosis has opened up a window to the role NO may play
      in their pathogenesis and possible clinical benefits in the management of these
      diseases.

PMID- 20822992
TI  - Respiratory function in an obese patient with sleep-disordered breathing.

PMID- 20822993
TI  - Electronic medical records: a practitioner's perspective on evaluation and
      implementation.
AB  - This article describes the initial and ongoing efforts of our pulmonary medicine
      practice to deploy an electronic medical records (EMR) system. Key factors in the
      vendor selection and implementation process included (1) identification and
      commitment to long-term goals for EMR; (2) dedicated resources, including both
      physician and nonphysician champions to lead the design and implementation teams;
      and (3) ample patience and time allotted to achieve the desired results: a fully
      functional system that enhances quality, improves operational efficiency, and
      reduces costs. An EMR scorecard including multiple system attributes was designed
      to facilitate vendor comparisons. Perseverance, patience, and compromise were
      necessary to overcome the challenge of changing the behavior of providers and
      support staff. We have accomplished improvements in workflow automation and
      reductions in staff hours, office supplies, file space, and transcription costs.
      Our system lacks pulmonary-specific templates and prompts for work flow and
      clinical decision making. We have directed internal resources and outsourced
      professional support to design these features as our practice strives to enhance
      our quality of care with pulmonary disease management that conforms to national
      guidelines.

PMID- 20822991
TI  - Workshop on idiopathic pulmonary fibrosis in older adults.
AB  - Idiopathic pulmonary fibrosis (IPF), a heterogeneous disease with respect to
      clinical presentation and rates of progression, disproportionately affects older
      adults. The diagnosis of IPF is descriptive, based on clinical, radiologic, and
      histopathologic examination, and definitive diagnosis is hampered by poor
      interobserver agreement and lack of a consensus definition. There are no
      effective treatments. Cellular, molecular, genetic, and environmental risk
      factors have been identified for IPF, but the initiating event and the
      characteristics of preclinical stages are not known. IPF is predominantly a
      disease of older adults, and the processes underlying normal aging might
      significantly influence the development of IPF. Yet, the biology of aging and the
      principles of medical care for this population have been typically ignored in
      basic, translational, or clinical IPF research. In August 2009, the Association
      of Specialty Professors, in collaboration with the American College of Chest
      Physicians, the American Geriatrics Society, the National Institute on Aging, and
      the National Heart, Lung, and Blood Institute, held a workshop, summarized
      herein, to review what is known, to identify research gaps at the interface of
      aging and IPF, and to suggest priority areas for future research. Efforts to
      answer the questions identified will require the integration of geriatrics,
      gerontology, and pulmonary research, but these efforts have great potential to
      improve care for patients with IPF.

PMID- 20822994
TI  - Hypersensitivity pneumonitis due to molds in a saxophone player.
AB  - This 48-year-old patient was evaluated for an interstitial pneumonia. An open
      lung biopsy showed a pattern of nonspecific interstitial pneumonia. The CT scan
      appearance, showing mosaic ground-glass opacities in the ventilated parts of the
      lung, the centrolobular predominance of inflammation on the lung sections, and
      the presence of a lymphocytic alveolitis at BAL suggested a hypersensitivity
      pneumonitis. The patient was a white-collar worker and had no contact with pets,
      birds, drugs, or molds at home. He used to play the saxophone as a hobby. Two
      molds, Ulocladium botrytis and Phoma sp, were detected in the saxophone.
      Precipitating antibodies to these molds were present in his serum. An additional
      study confirmed the frequent colonization of saxophones with potentially
      pathogenic molds, such as Fusarium sp, Penicillium sp, and Cladosporium sp.
      Respiratory physicians should be aware of the risk of hypersensitivity
      pneumonitis in saxophone or perhaps other wind instrument players.

PMID- 20822995
TI  - Azygos vein to pulmonary vein fistula is a pathway for cerebral embolism.
AB  - A 43-year-old man was admitted for right upper and lower limb weakness and
      aphasia. He had suffered dizziness and transient blindness 6 months ago and had
      also been found lying in the bathroom on another occasion. Multiple cerebral
      infarctions were confirmed by brain CT scan and MRI. Diffuse nodes in the
      mediastinum and postperitoneum had been found in pulmonary CT scans and MRI scans
      since 1999. Pulmonary CT scan revealed multiple bilateral pneumatoceles in the
      lungs. Contrast CT scan showed an enlarged azygos vein on the right side of the
      spinal column and an enlarged azygos arch. CT scan-guided biopsy revealed a few
      fibers, fat, and vascular tissues in the mass. Transcranial Doppler bubble test
      showed gas microembolic signals in both middle cerebral arteries. Pulmonary
      digital subtraction angiogram confirmed an enlarged azygos vein. A fistula was
      found between the pulmonary and azygos veins with turbulent flow from pulmonary
      to azygos at rest. Cavography revealed that the pulmonary vein appeared
      simultaneously with the superior cava vein during Valsalva maneuver. In summary,
      the pathway of cerebral embolism was based on three pathologic mechanisms: (1)
      increased inferior vena cava pressure, (2) enlarged right azygos aneurysm, and
      (3) the presence of a fistula between the azygos and pulmonary veins.

PMID- 20822996
TI  - Two cases with pulmonary mucosa-associated lymphoid tissue lymphoma successfully
      treated with clarithromycin.
AB  - A 70-year-old woman with a history of sinobronchial syndrome was admitted to the
      hospital because of a cough, sputum, and abnormal chest shadow. She was diagnosed
      with pulmonary mucosa-associated lymphoid tissue lymphoma (p-MALToma) based on
      results of a pathologic examination and the gene rearrangements in the Ig heavy
      chain on Southern blot hybridization. Although p-MALToma did not regress with
      conventional therapy, it was reduced after long-term treatment with
      clarithromycin (CAM) (200 mg/d). A 57-year-old woman with a history of Sjogren
      syndrome and lymphocytic interstitial pneumonia had a mass lesion in the left
      lower lung field. CT image-guided biopsy established a diagnosis of p-MALToma.
      The p-MALToma regressed with long-term treatment with CAM (200 mg/d), whereas
      Helicobacter pylori (HP) eradication therapy was not effective in concurrent
      atrophic gastritis with HP. It is suggested that CAM, a macrolide antibiotic, may
      be effective in some patients with p-MALToma.

PMID- 20822997
TI  - Hypothesis testing, study power, and sample size.

PMID- 20822998
TI  - Metastatic papillary thyroid carcinoma and severe airflow obstruction.

PMID- 20822999
TI  - A 61-year-old man with unexplained daytime and nighttime hypoxia.

PMID- 20823000
TI  - A 30-year-old man with facial flushing and a mediastinal mass.

PMID- 20823005
TI  - Dr Friedrich Wegener and the American College of Chest Physicians Award.

PMID- 20823006
TI  - Trombone player's lung: a probable new cause of hypersensitivity pneumonitis.

PMID- 20823007
TI  - Clinical implications of MRI to assess cardiac and pulmonary function in patients
      with duchenne muscular dystrophy.

PMID- 20823008
TI  - Association of chronic mountain sickness with abnormal pulmonary
      microcirculation: importance of adjusting predicted diffusing capacity of the
      lung for carbon monoxide for altitude, hemoglobin, and lung volume.

PMID- 20823009
TI  - How to compare two different metered-dose inhaler-valved holding chambers in the
      administration of salbutamol.

PMID- 20823010
TI  - Occlusion and malposition of small-bore chest tubes for pleural infection.

PMID- 20823011
TI  - Standardization of interventional pulmonology training.

PMID- 20823012
TI  - Duchenne muscular dystrophy.

PMID- 20823013
TI  - Commissioners doing it for themselves.

PMID- 20823014
TI  - Mentally disordered or lacking capacity? Lessons for management of serious
      deliberate self harm.

PMID- 20823015
TI  - Advance directives and suicidal behaviour.

PMID- 20823016
TI  - Preventing dementia. Targeting depressive symptoms is unlikely to help.

PMID- 20823017
TI  - Preventing dementia. Bridging theory and reality gap.

PMID- 20823018
TI  - When is restraint appropriate? An American view.

PMID- 20823019
TI  - Media training for researchers. A win-win situation.

PMID- 20823020
TI  - Risks of working time directive. Shorter shifts and more frequent handover.

PMID- 20823021
TI  - FDA on rosiglitazone. More on advisory committee decision.

PMID- 20823025
TI  - Friends of man who went to Dignitas clinic wait to see if they will be
      prosecuted.

PMID- 20823026
TI  - Pharmacists would like compensation for expanded role in patient care.

PMID- 20823027
TI  - Expanding phenotype and clinical analysis of tyrosine hydroxylase deficiency.
AB  - This study included 12 Chinese patients with a wide spectrum of phenotypes of
      tyrosine hydroxylase deficiency. Seven females and 5 males, aged 2.2 to 41 years,
      had phenotypes ranging from severe type with onset at infancy to mild type with
      onset after 3 years of age. Patients with the severe type had encephalopathy with
      poor treatment response or infantile parkinsonism with motor delay. Patients with
      the less common mild type had dopa-responsive dystonia or a newly recognized
      predominant symptom of myopathy. Female siblings had more severe phenotypes. The
      phenotype and treatment outcomes were strongly related to a homovanillic acid
      level and homovanillic acid/5-hydroxyindolacetic acid ratio of less than 1 in the
      cerebrospinal fluid. Hyperprolactinemia was found in 50% of the severe cases.
      Levodopa was the mainstay of treatment, and early addition of selegiline resulted
      in a remarkable response in some patients. Treatment response for mild-type
      patients is universally good even with a treatment delay of 10 years after onset
      of neurological symptoms.

PMID- 20823028
TI  - Acute necrotizing encephalopathy of childhood with spinal cord involvement: a
      case report.
AB  - Acute necrotizing encephalopathy of childhood is a rare acute encephalopathy
      occurring after febrile illness with subsequent rapid deterioration of
      consciousness and convulsions. Typical brain magnetic resonance imaging (MRI)
      findings are symmetric involvement of the bilateral thalami, brainstem, and
      cerebral periventricular white matter or the cerebellum. Spinal cord involvement
      has never been reported. This report describes a healthy 2-year-old girl, who
      displayed typical clinical manifestations of acute necrotizing encephalopathy.
      Brain MRI demonstrated symmetrical lesions over the bilateral thalami and
      periventricular white matter. The clinical features and radiologic images
      suggested spinal cord involvement. This is the first reported case of acute
      necrotizing encephalopathy with spinal cord involvement. Spinal cord lesions are,
      therefore, possible in cases of acute necrotizing encephalopathy of childhood,
      and these require special attention.

PMID- 20823029
TI  - Relapsing acute disseminated encephalomyelitis in children: further evaluation of
      the diagnosis.
AB  - We examined our cases of relapsing acute disseminated encephalomyelitis (n = 13)
      in which diagnosis was made before the publication of the International Pediatric
      Multiple Sclerosis Study Group criteria in 2007, with the aim of reevaluating the
      primary diagnosis, examining any features indicative of other disorders, and
      determining the final diagnosis. Mean duration of follow-up was 9.4 (range, 2-20)
      years. Most (n = 11) were multiphasic, and 2 were recurrent cases. The final
      diagnosis changed in only 2 patients, both in the multiphasic group: one multiple
      sclerosis, and one other possible central nervous system vasculitis. All others
      are still being followed up as relapsing acute disseminated encephalomyelitis and
      had no further attacks. Six patients in this category did not have encephalopathy
      at first episode, which suggested the requirement for encephalopathy might be
      restrictive for certain cases. These results suggest the diagnosis of relapsing
      acute disseminated encephalomyelitis can be made correctly in most cases by
      clinical and imaging features.

PMID- 20823030
TI  - Experience with hyperphenylalaninemia in a developing country: unusual clinical
      manifestations and a novel gene mutation.
AB  - We report our experience in a cohort of patients with hyperphenylalaninemia in a
      tertiary care referral center in Lebanon. Forty-one sequential patients were
      studied: 34 classical phenylketonuria (PKU), 3 hyperphenylalaninemia (non-PKU),
      and 4 biopterin metabolism defects. The majority of cases were clinically
      diagnosed at variable ages with variable neurological outcomes. Only 29.3% were
      detected by neonatal screening. Two unusual cases were observed in the context of
      inadequate treatment in 1 and delayed therapy in the other: a newborn with PKU
      developed severe keratomalacia; and a 5-year-old girl with dihydropteridine
      reductase deficiency due to a novel mutation identified in the quinoid
      dihydropteridine reductase gene developed Lennox-Gastaut syndrome and white
      matter changes with periventricular cysts. Part of our experience parallels that
      in the West. However, the clinical manifestations observed in our patients
      emphasize the importance of a national newborn screening program with efficient
      management of diagnosed cases.

PMID- 20823031
TI  - Depressed brainstem auditory function in children with cerebral palsy.
AB  - Brainstem auditory evoked responses were studied to examine brainstem auditory
      function in 80 children with cerebral palsy. The response waveform, particularly
      later waves, tended to be depressed. Thirty-three (41.3%) showed abnormal
      results. The main abnormality was reduced wave V amplitude. Other abnormalities
      were decreased V/I amplitude ratio, missing waves, prolonged I-V interval, and
      increased interaural difference in I-V interval. The abnormalities were
      persistent during the follow-up. In contrast to common findings in the responses
      in progressive neurologies, abnormalities in interpeak intervals were rare in
      children with cerebral palsy. There were some characteristic changes in the
      responses in certain etiologies. These results suggest that brainstem auditory
      function in children with cerebral palsy is depressed, which may be owing to
      decreased or altered neural firing or synchrony in the auditory brainstem. A
      detailed analysis of central components of the responses is valuable in detecting
      central auditory dysfunction in children with cerebral palsy.

PMID- 20823032
TI  - Dandy-Walker malformation masking the molar tooth sign: an illustrative case with
      magnetic resonance imaging follow-up.
AB  - Joubert syndrome is a disorder characterized by ataxia, developmental delay,
      oculomotor anomalies, and breathing irregularities, with cerebellar vermian and
      midbrain dysgenesis. The molar tooth sign, reflecting the midbrain dysgenesis of
      Joubert syndrome, is the neuroradiological hallmark and is an essential sign in
      the identification of this condition. Variable vermian agenesis, an expanded
      fourth ventricle, and a large posterior cranial fossa with a normal brainstem are
      typical of Dandy-Walker malformation. The authors report a case in which a Dandy
      Walker malformation coexisted with Joubert syndrome, but initially prevented the
      ''molar tooth sign'' from being recognized because of an important cystic
      dilatation of the fourth ventricle. In this article, they discuss the importance
      of the re-examination of brain magnetic resonance features after decompression of
      the posterior cranial fossa in a patient with Dandy-Walker malformation and
      additional clinical neurological or systemic abnormalities typical of Joubert
      syndrome, to not miss the correct diagnosis.

PMID- 20823033
TI  - Association of rapidly progressive moyamoya syndrome with bevacizumab treatment
      for glioblastoma in a child with neurofibromatosis type 1.
AB  - Neurofibromatosis type 1 is a common multisystemic disorder that can result in
      tumors of the central and peripheral nervous system. Individuals with
      neurofibromatosis type 1 are also at increased risk to develop moyamoya syndrome,
      which is a cerebrovascular condition that predisposes affected individuals to
      develop strokes as a result of progressive narrowing of the intracranial internal
      carotid arteries and failure of adequate blood supply through collateral vessels.
      We report a case of a young boy with neurofibromatosis type 1 with glioblastoma
      who developed rapidly progressive moyamoya vasculopathy after treatment with the
      angiogenesis inhibitor bevacizumab.

PMID- 20823034
TI  - A clinical picture of Guillain-Barre syndrome in children in the United States.
AB  - The authors describe the demographics, clinical presentation, investigation,
      treatment, and outcomes of pediatric patients with Guillain-Barre syndrome. They
      identified 35 pediatric patients with Guillain-Barre syndrome presenting to a
      tertiary academic center over a 20-year period. The most common presenting
      symptoms were paresthesias (54%), weakness (49%), and myalgias (49%). Sensation
      was affected in 54% of patients, and hyporeflexia or areflexia was present in 94%
      of patients. Cranial nerve dysfunction (46%) and autonomic involvement (eg,
      changes in blood pressure, pulse, bowel/bladder control, or priapism; 46%) were
      also common. Autonomic dysfunction, cranial nerve involvement, and
      albuminocytological dissociation were significantly associated with a decreased
      time to nadir, the point when symptoms peaked (P = .015, .007, and .005,
      respectively). Although not statistically significant, treatment with
      plasmapheresis had a better success rate than intravenous immunoglobulin. The
      authors' results will help to further delineate the clinical picture of Guillain
      Barre syndrome in children and refine treatment strategies.

PMID- 20823035
TI  - Thyroid mass in children and adolescents living in the most exposed areas to
      Chernobyl fallout in Belarus.
AB  - This paper aims to determine the thyroid volumes in children and teenagers living
      in Gomel and Mogilev Oblasts, which are the areas of Belarus that were most
      affected by the Chernobyl accident. Results of thyroid volume measurements
      performed in 1991-1996 by the Sasakawa Memorial Health Foundation were used to
      evaluate the variation by age of the thyroid volumes for girls and boys aged from
      5 to 16 y. Thyroid volumes for age groups without measurements were also
      estimated. For a given age and gender, the differences between children from
      Gomel and Mogilev Oblasts do not exceed 12 %, which is relatively small when the
      variability of individual values is considered. For children of a given age, the
      individual values show a variability characterised by geometric standard
      deviation (GSD) of 1.25-1.4. Values of thyroid mass that were derived from the
      measured thyroid volumes are being used within the framework of the on-going
      Belarusian-American cohort study of thyroid cancer and other thyroid diseases
      after the Chernobyl accident to estimate with more accuracy the thyroid doses
      that were received by the cohort members.

PMID- 20823036
TI  - Semi-empirical relationship for photon buildup factor in soft tissue and water.
AB  - Buildup factor of gamma and X-ray photons in the energy range of 0.2-2 MeV in
      water and soft tissue is computed using Monte Carlo code MCNP4C. The results are
      compared with the buildup factor data of pure water. A new relationship
      estimating buildup factor as a function of penetration depth, Compton scattering
      and energy absorption cross sections is introduced. The new relationship
      estimates buildup factor with 5 % deviation compared with the existing data.

PMID- 20823037
TI  - Development of a medical resource database for radiological emergency
      preparedness.
AB  - In order for Canada to be better prepared to respond quickly to a radiological or
      nuclear emergency detailed knowledge regarding the locations and capacities of
      hospitals, relevant medical supplies and radiological or nuclear professionals is
      needed. These key points of information were identified at a CRTI workshop in
      2009, and it was proposed that a medical resource database (MRD) was required.
      This database is in addition to the development of a radiation accident registry
      which was also proposed at the CRTI Workshop in 2009. The MRD has been designed,
      built and populated where possible; it is now ready for field testing and
      deployment. The creation of the database is one more step towards a better and
      more effective response in a radiological or nuclear emergency. In order to
      maintain this database and keep it up to date, contributions from all levels of
      radiation protection professionals will be needed. In this paper, the database
      structure and the data collected will be presented and discussed.

PMID- 20823038
TI  - Do we all understand the ambient dose equivalent in the same way?

PMID- 20823039
TI  - Evaluation of mean glandular dose in a full-field digital mammography unit in
      Tabriz, Iran.
AB  - This study was aimed at evaluating the mean glandular dose (MGD) and affecting
      factors during mammography examinations by a full-field digital mammography unit.
      An extensive quality control program was performed to assure that the unit is
      properly working. Required information including compressed breast thickness
      (CBT), breast parenchymal pattern and technical factors used for imaging were
      recorded. An entrance skin exposure measurement was also performed using slabs of
      polymethylmethacrylate with 2-8 cm thickness. On the basis of recorded
      information and measured data, the MGD was estimated for 1145 mammography
      examinations obtained from 298 patients. Mean CBTs of 4.9 and 5.8 cm and MGDs of
      2 and 2.4 mGy were observed for craniocaudal and mediolateral oblique views,
      respectively. Significant correlation was seen between MGD and CBT, breast
      parenchymal pattern and applied kVp and mAs.

PMID- 20823040
TI  - Carotid sinus hypersensitivity: disease state or clinical sign of ageing?
      Insights from a controlled study of autonomic function in symptomatic and
      asymptomatic subjects.
AB  - AIMS: This study sought to improve the currently limited understanding of the
      pathophysiology of carotid sinus hypersensitivity (CSH) by comparing autonomic
      function measured by heart rate variability (HRV) and baroreflex sensitivity
      inpatients with symptomatic CSH and asymptomatic individuals with and without
      CSH. METHODS AND RESULTS: Twenty-two patients with symptomatic CSH, 18
      individuals with asymptomatic CSH, and 14 asymptomatic older individuals without
      CSH were recruited to our study. Non-invasive measurements of heart rate and
      blood pressure were obtained during 10 min of supine rest. Low frequency (LF),
      high frequency (HF), and total power spectral density (PSD) for HRV were
      determined using the autoregressive method. The baroreflex slope (BRS) and
      baroreflex effectiveness index (BEI) were determined using the sequence method
      for baroreflex sensitivity. There were significant increases in the LF-HRV (P =
      0.014), total PSD (P = 0.031), LF:HF (P = 0.047), normalized (nu) LF-HRV (0.049),
      down ramp BEI (P = 0.017), and total BEI (P = 0.038) in the symptomatic CSH group
      compared with non-CSH controls. The asymptomatic CSH group had significantly
      higher LF-HRV (P = 0.001), total PSD (P = 0.002), nuLF-HRV (P = 0.026), and LF:HF
      (P = 0.030), as well as up, down, and total BRS (P = 0.012, P = 0.015, and P =
      0.011, respectively) and BEI (P = 0.049, P = 0.001, and P = 0.006, respectively)
      than non-CSH control participants. CONCLUSION: This study has demonstrated an
      association between CSH with increased resting sympathetic activity and
      baroreflex sensitivity regardless of the presence of symptoms, indicating the
      presence of autonomic dysregulation in individuals with CSH. Our findings
      therefore suggest that CSH is part of a generalized autonomic disorder but do not
      differentiate between asymptomatic and symptomatic individuals.

PMID- 20823041
TI  - Anatomical variations of the right coronary artery may be a source of difficult
      block and conduction recurrence in catheter ablation of common-type atrial
      flutter.
AB  - AIMS: Although Eustachian valves and recesses have been related to resistance to
      block, the effect of convective cooling by the right coronary artery (RCA) has
      not been evaluated in the clinical setting. METHODS AND RESULTS: The distance and
      course of the RCA in relation to the cavotricuspid isthmus (CTI) in addition to
      variants of CTI anatomy and the presence of Eustachian valves were analysed from
      computed tomography scans of 54 patients. Ablation power was titrated using a
      step-up protocol. Invasive follow-up was available for 34 patients. The RCA came
      closest to the CTI inferiorly separated by a mean of 5.3 +/- 2.5 mm compared with
      7.3 +/- 3.3 mm septally and 5.7 +/- 2.3 mm anteriorly (P < 0.01). The maximum
      power required for CTI block correlated inversely with the distance of the RCA to
      the CTI, whereas the cumulative energy was highest in the presence of recesses.
      Neither failure of acute block nor a higher rate of conduction recurrence could
      be attributed to variants of CTI anatomy or the presence of a Eustachian valve.
      Using multivariate analysis, a position of the RCA underneath the central part of
      the CTI was the only significant predictor for late conduction recurrence. These
      patients showed a 2.7 mm larger distance of the RCA to the tricuspid valve plane
      (P = 0.05). CONCLUSION: The RCA affects CTI ablation as higher power settings are
      required at closer distances to the ablation site. Late conduction recurrences
      were observed in patients with a variation of the RCA, leaving the
      atrioventricular groove towards the atrial aspect.

PMID- 20823042
TI  - Impact of variant pulmonary vein anatomy and image integration on long-term
      outcome after catheter ablation for atrial fibrillation.
AB  - AIMS: To investigate the impact of variant pulmonary vein (PV) anatomy and the
      use of three-dimensional image integration (3D-II) on long-term efficacy of
      catheter ablation for atrial fibrillation (AF). METHODS: Consecutive procedures
      from 2002 to 2007 were analysed from a prospective database. All patients
      underwent wide area circumferential ablation, with linear lesions added and
      complex fractionated electrograms targeted for persistent AF. Imaging was
      segmented on Carto to assess PV anatomy. RESULTS: Three hundred and fifty
      patients underwent 1.9 +/- 0.9 procedures. The mean age was 57 +/- 11 years, 73%
      males, and 55% paroxysmal AF. Freedom from AF/atrial tachycardia was 42% for
      paroxysmal AF and 20% for persistent AF at 3.1 years after the first procedure,
      or 86 and 66%, respectively, at 2.5 years after the last procedure. The Kaplan
      Meier analysis showed a trend towards improved single-procedure efficacy with 3D
      II (8.9% difference, P = 0.087) and a reduction in the number of procedures per
      patient from 2.1 +/- 1.1 to 1.8 +/- 0.9 (P < 0.0001). The use of 3D-II improved
      single-procedure efficacy with Carto (13.3% difference, P = 0.018), but not with
      Ensite NavX. Variant PV anatomy was identified in 28% and was associated with a
      lower single-procedure efficacy (10.0% difference, P = 0.024) but with no effect
      on final outcome. Multivariate analysis confirmed the impact of 3D-II [hazard
      ratio (HR) for recurrence of AF 0.67, P = 0.020] and variant PV anatomy (HR 1.37,
      P = 0.044). CONCLUSION: The use of 3D-II improves single-procedure efficacy of PV
      isolation for AF. Variant PV anatomy was associated with a lower single-procedure
      success rate.

PMID- 20823043
TI  - Predictors of costs related to cardiovascular disease among patients with atrial
      fibrillation in five European countries.
AB  - AIMS: To estimate predictors of direct costs and costs of hospitalization related
      to cardiovascular disease (CVD) in patients with atrial fibrillation (AF)
      recruited to the Euro Heart Survey on AF (EHS-AF) in Greece, Italy, Poland,
      Spain, and the Netherlands. METHODS AND RESULTS: Annual direct costs were
      modelled by country using ordinary least squares (OLS) regression. For costs of
      hospitalization related to CVD, logistic regressions followed by conditional OLS
      regression were employed. In each case, effects of the following potential
      explanatory variables were tested: age, sex, body mass index, type of AF,
      diabetes, hypertension, myocardial infarction (MI), angina pectoris (AP),
      valvular heart disease (VHD), congestive heart failure (CHF), stroke, and/or
      other underlying heart disease at the time of enrolment in the EHS-AF. Estimated
      direct annual costs for the reference EHS-AF patient (female aged <65 years with
      first-detected AF and no co-morbidities at baseline) were ?933 in Greece, ?1383
      in Italy, ?698 in Poland, ?1316 in Spain, and ?1544 in the Netherlands. The co
      morbidities identified as predictors of direct costs were VHD in Greece, Italy,
      and Spain, AP in Italy and Spain, diabetes and stroke in Poland, CHF in Italy, MI
      in Spain and other underlying heart disease in Poland and the Netherlands. For
      costs of CVD-related hospitalization, the most important co-morbidity identified
      as a predictor was VHD. CONCLUSION: The results reported in this study increase
      the understanding of the cost structure of CVD in AF patients and may therefore
      inform the targeting of intervention therapy in selected groups of at-risk
      patients.

PMID- 20823044
TI  - Genetics of lone atrial fibrillation.

PMID- 20823045
TI  - Overweight and obesity in Sweden. A five year follow-up, 2004-2008.
AB  - OBJECTIVE: The number of overweight and obese persons increased through the 1980s
      and 1990s in Sweden, for instance for men from 35% in 1980 to 52% in 2007. This
      study investigated whether this trend continued over the past 5 years, including
      trends for diet and physical activity. MATERIALS AND METHODS: The sampling frame
      in these surveys was established from the Swedish National Registry where all
      people registered in Sweden between 18 and 84 years in 2004 and 16-84 years in
      2005-08 were included. RESULTS: There were no changes in the number of overweight
      (approximately 42% for men and 27% for women) and obese (approximately 11% for
      both men and women) persons between 2004 and 2008. Approximately 65% of the men
      and 64% of the women were physically active for an average of 30 minutes per day
      in 2008. Thirteen percent of women and 5% of men reported consuming at least five
      servings of fruit and vegetables per day during the 5-year period. CONCLUSIONS:
      Sweden seems to have reached a steady state regarding overweight and obesity. It
      would probably be fruitful to further discuss life-style issues, such as diet and
      physical activity, in the Swedish healthcare system and how to deal with the
      social gradient.

PMID- 20823046
TI  - Associations of high-risk behaviour and HIV status with HIV knowledge among
      persons in Tallinn, Estonia.
AB  - AIM: The aim of this study was to determine the associations between the level of
      HIV knowledge, HIV-related risk behaviours, and HIV status among persons
      receiving voluntary counselling and testing services in Tallinn, Estonia. DESIGN:
      A cross-sectional study design was used. METHODS: A total of 772 subjects
      completed a 47-item questionnaire gathering information on demographics, HIV
      related risk behaviours, and HIV-related knowledge. Participant's HIV status was
      determined by an anonymous rapid test. Only incident HIV cases were included in
      regression analyses. An analysis of covariance (ANCOVA) modelling evaluated
      associations between HIV knowledge and high-risk behaviours while multivariable
      logistic regression assessed association between HIV status and HIV knowledge.
      RESULTS: The final ANCOVA model indicates that HIV risk behaviours are
      significantly associated with HIV knowledge (p = 0.01). Compared to participants
      with no identified high-risk behaviour, the adjusted mean score of HIV knowledge
      was higher among persons sharing injection equipment (p = 0.05), and persons
      engaging in unprotected heterosexual intercourse (p = 0.03); there was no
      statistical difference observed among men engaging in unprotected sex with other
      men. Women had higher mean scores than men (p = 0.01) and persons of ''other''
      ethnicities had a higher mean knowledge score than ethnic Estonians (p = 0.01)
      and Russians (p < 0.01). Logistic regression indicated that mean knowledge was
      higher among participants who tested HIV positive (OR = 1.42; 95% CI = 1.12
      1.87). CONCLUSIONS: In this sample, higher knowledge scores were not associated
      with lower infection rates. These results indicate the importance of targeting
      all high-risk groups in HIV prevention and education programmes.

PMID- 20823047
TI  - Construct validity of a revised Physical Activity Scale and testing by cognitive
      interviewing.
AB  - AIM: To validate the construct validity of a new version of a Physical Activity
      Scale (PAS 2) for measuring average weekly physical activity of sleep, work, and
      leisure time to determine whether a further criterion validation is justified.
      METHODS: The validity of responses to the questionnaire was evaluated by
      cognitive interviewing in 16 Danish men and women aged 21-70 years. Construct
      validity was validated in 342 men and women aged 35-66 years by assessing
      agreement between 24-h MET-scores obtained from average weekly physical activity
      measured by PAS 2 and a 24-h Physical Activity Scale (PAS 1), previously found to
      overestimate physical activity. RESULTS: Cognitive interviewing revealed few
      problems in the questions on physical activity in different domains. No problems
      regarding the structure of the questionnaire were identified. The agreement
      between PAS 1 and PAS 2 MET-scores was high among participants with a PAS 1 24-h
      MET-score <45 MET-hours. Among participants with a PAS 1 24-h MET-score >=45 MET
      hours, the weekly-based scale, PAS 2, systematically estimated fewer MET-hours
      compared to the 24-h based scale, PAS 1. The difference increased proportionally
      with the average of the two MET-scores. CONCLUSIONS: Few, small, lexical
      revisions were implemented into the new scale to improve the validity. As
      hypothesized, PAS 2 produced lower estimates of energy expenditure compared to
      PAS 1, indicating that the new scale may provide more valid measurements and that
      further validation against an objective criterion is justified.

PMID- 20823048
TI  - Incidence and risk factors of clinically significant chemotherapy-induced
      thrombocytopenia in patients with solid tumors.
AB  - PURPOSE AND RELEVANCE: Chemotherapy-induced thrombocytopenia (CIT) can be a
      significant problem in patients with cancer, leading to numerous clinical
      complications. Understanding the types of patients at risk for these
      complications is essential to improve monitoring, counseling, and provide future
      targeted prophylaxis measures. Previous studies have limited prospective utility
      since they do not examine risk factors associated with complications from multi
      agent regimens. This evaluation aims to identify the incidence and risk factors
      associated with clinical complications of CIT in patients receiving common
      chemotherapy regimens. METHODS: Retrospective evaluation of adult patients
      receiving first or second line regimens for the most common solid tumors
      associated with high rates (>=5%) of laboratory diagnosed thrombocytopenia.
      Patients were examined for clinically significant CIT (defined as platelet count
      <75,000 cells/uL as well as the presence of one of the following: bleeding, dose
      reduction/delay, platelet transfusion, or therapy cessation) and associated risk
      factors. RESULTS: About 254 patients receiving a total of 278 regimens were
      evaluated. The incidence of clinically significant CIT=10.1%; complications were
      most common in patients receiving cisplatin/gemcitabine for bladder cancer (57%),
      or carboplatin/gemcitabine (29%) or cisplatin/etoposide (18%) for lung cancer.
      Bladder cancer (OR=13.7 (2.89-64.7); p=0.001) and concurrent or recent infection
      (OR=3.8 (1.45-10.1); p=0.007) was found to increase the risk of clinical
      complications while smoking was found to have a protective effect (OR=0.17 (0.04
      0.71)). CONCLUSIONS: The incidence of clinically significant CIT is most commonly
      seen in patients using cisplatin/gemcitabine for bladder cancer, or
      carboplatin/gemcitabine or cisplatin/etoposide for lung cancer. Further
      evaluation of these patients is warranted.

PMID- 20823049
TI  - Occupational exposure to antineoplastic drugs in seven Italian hospitals: the
      effect of quality assurance and adherence to guidelines.
AB  - In health care facilities, dermal contact and inhalation are considered to be the
      main routes of exposure to cytotoxic antineoplastic drugs (ADs). Hand-to-mouth
      contamination or accidental needle sticks as well as events due to inadequate
      disposal may also contribute to exposure. In order to measure the extent of
      contamination, biological and environmental monitoring are essential tools for
      routine testing. Moreover, reliable sampling and analytical procedures are
      required. During the last decade, several methods have been developed and
      validated. The appropriate analytical techniques were used to quantify even very
      low levels of some of the more commonly used ADs, such as cyclophosphamide, 5
      fluoruracil, taxol, anthracyclines, and platinum-compounds. The main objective of
      this study is to assess the adherence to existing standards of practice through
      an effective monitoring program, including environmental and biological
      measurements. In seven hospitals located in Northern-Central Italy, periodic
      surveys were scheduled to verify continuing compliance with guidelines over a 5
      year period. All biological samples were found to be below detection limits and a
      progressive, significant decrease in workplace contamination was observed. Our
      results confirm that a cost-effective monitoring regime, including fast and
      simple sample pre-treatment procedures, simultaneous determination of the
      analytes and their metabolites, validated procedures including uncertainty
      evaluation, and periodic surveys, is the adequate approach for the collection of
      reliable exposure data and hence for effective intervention.

PMID- 20823050
TI  - The efficiacy of bismuth subnitrate against genotoxicity and oxidative stress
      induced by aluminum sulphate.
AB  - Aluminum (Al) is commonly used in industrial processes and drugs and is thought
      to induce erythrocytes damage via activation of oxidative stress. Recently,
      bismuth (Bi)-containing drugs are used in the treatment of various diseases.
      However, uncertain effects of Bi in blood tissue may participate in the
      therapeutic efficacy of Bi compounds as related to metals. Hence, this study
      aimed to determine the roles on human blood cells of the various concentrations
      of aluminum sulphate (Al(2)(SO(4))(3)) and bismuth subnitrate (BSN), separate and
      together. With this aim, oxidative status was assessed on erythrocytes by
      measuring following oxidative stress markers: reduced glutathione (GSH),
      superoxide dismutase (SOD), glucose-6-phosphate dehydrogenase (G-6-PDH) and
      catalase (CAT). Two chemicals were tested for their ability to induce cytogenetic
      change in human lymphocytes using assays for chromosome aberrations (CAs) and
      sister chromatid exchanges (SCEs). Our results showed that high dose of
      Al(2)(SO(4))(3) (20 ug/mL) caused oxidative stress and increased CA and SCE
      frequencies. Whereas, BSN doses did not change CA and SCE rates. Moreover, it led
      to changes of antioxidant capacity at different concentrations. After concomitant
      treatment with Al(2)(SO(4))(3) and BSN, the effects of BSN doses were different
      on enzyme activities and decreased the genotoxic damage. However, the high dose
      of BSN and Al(2)(SO(4))(3) was shown to enhance the frequencies of CAs and SCEs
      in a synergistic manner. In conclusion, BSN could be effective in the protection
      against the blood toxicity of Al(2)(SO(4))(3).

PMID- 20823051
TI  - The possible effect of diets containing Nigella sativa and Thymus vulgaris on
      blood parameters and some organs structure in rabbit.
AB  - Because of the increasing cost of animal feed ingredients as well as the high
      demand, especially for the protein supplements, several efforts were carried out
      to use untraditional feed protein ingredients to participate in facing feed
      shortage problem and at the same time to decrease feeding costs. Nigella sativa
      (black cumin) and Thymus vulgaris are the most famous medical plants that have
      attracted the attention of many investigators for long time. The present study
      aimed to evaluate the possible effects of a partial replacement of soybean meal
      in control diet by Nigella sativa and/or Thymus vulgaris on the possible harmful
      changes in histological structure of some organs and blood parameters in growing
      New Zealand White rabbits. Blood constituents showed that the percentages of
      hemoglobin, hematocrate, the mean corpuscular hemoglobin and white blood cells
      (WBCs) count were significantly increased with the presence of black cumin seeds
      in the diets while WBCs count and the mean corpuscular volume in rabbit blood
      tends to decrease in Thymus vulgaris diets. Feeding diet supplemented with
      Nigella sativa increased the plasma total proteins, albumin, globulin, serum
      glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate
      transaminase (SGPT) and decreased total lipids, cholesterol and triglycerides.
      The use of Nigella sativa alone or either mixture with Thymus vulgaris are good
      supplements for growing rabbits without any adverse effect on histological
      structure of liver, kidney and testis in rabbits.

PMID- 20823053
TI  - Effects of 50 Hertz-1 mT magnetic field on action potential in isolated rat
      sciatic nerve.
AB  - The aim of this study was to investigate possible effects of 50 Hz-1 mT magnetic
      field (MF) on action potential in isolated rat sciatic nerve. We used 16 Wistar
      rats in the study. They were divided into control (n = 10) and MF (n = 6) groups.
      The sciatic nerve of left legs in the MF group was exposed to 50 Hz-1 mT MF for
      30 min by using a Helmholtz applicator and then action potentials in control and
      experimental groups were recorded extracellularly. Maximum amplitude and
      hyperpolarization time and action potential were significantly (p <= 0.025) lower
      in the MF group than in control. However, conduction time, minimum amplitude,
      depolarization and repolarization times of the action potential was not different
      between control and MF groups evaluated. In conclusion, 50-1 mT MF caused to
      decrease amplitude value and hyperpolarization time of action potential in the
      rat nerve.

PMID- 20823052
TI  - Di-n-butyl phthalate (DBP) exposure induces oxidative stress in epididymis of
      adult rats.
AB  - Di-n-butyl phthalate (DBP) is a ubiquitous environmental pollutant, extensively
      used as a plasticizer in many products including plastics, cosmetics and medical
      devices. Previous studies have shown that DBP has potential testicular toxicity.
      Epididymis is known to play an important role in the maturation and storage of
      sperm. However, the effect and mechanism of action of DBP on epididymis is
      unclear. The present study was designed to investigate the effect of DBP on
      structure and function of epididymis in adult male rats by histological and
      biochemical study. Oxidative stress was also assessed in rat epididymis as an
      underlying mechanism. Forty SD adult rats were randomly allotted to four groups,
      and DBP was administered to each group by oral gavage at doses of 0 (control),
      100, 250 and 500 mg/kg/day for 2 consecutive weeks. The results indicated that
      the epididymal toxicity of DBP is dose-dependent. Epididymal weight, activities
      of epididymal alpha-glucosidase and glutathione peroxidase (GSH-Px) was
      significantly decreased in rats of 500 mg/kg DBP exposure group compared to the
      control. The activity of superoxide dismutase (SOD) was significantly decreased
      while the level of malondialdehyde (MDA) was significantly increased in the
      epididymal tissue of the 250 and 500 mg/kg DBP exposure groups compared with the
      control group. Moreover, microscopy with hematoxylin and eosin (HE) staining
      showed that atrophy of epididymal tubules, the interstitial vascular was
      hyperemia and the lumina were oligozoospermic in rats of 500 mg/kg DBP exposure
      group. In conclusion, DBP exposure alters the epididymal structure and function
      by inducing oxidative stress in epididymis of adult rats.

PMID- 20823054
TI  - Toxicity assessment of dye containing industrial effluents by acute toxicity test
      using Daphnia magna.
AB  - Toxicity of dye containing effluent of tannery, textile, dyes and pulp-paper
      industries was evaluated in an acute toxicity test using Daphnia magna. The 48
      hour EC(50) values were 4.33% and 19.5% for tannery effluents (Tn1 and Tn2).
      Textile effluents (Tx1-Tx7) had 48-hour EC(50) values; >100%, >100%, 62.9%,
      63.0%, 40.3%, >100% and >100%, respectively. Dye industries (D1-D7) had 48-hour
      EC(50) values; 14.1%, 15.5%, 24.5%, 29.7%, 23.2%, >100% and >100%, respectively.
      Similarly pulp-paper effluents (P1-P5) showed acute toxicity as 100%, 77.87%,
      46.44%, 69.55% and 82.84%, respectively. These results showed linear relationship
      with high degree of confidence (r(2) >= 0.84-0.99) between immobility and test
      concentrations. Toxicity classification criteria showed that out of five
      effluents from pulp-paper mill, four were minor acutely toxic having 48-hour
      EC(50) value in between >46%-100%. Out of seven textile effluents, four were not
      acutely toxic (48-hour EC(50) value >100%) and three were minor acutely toxic (48
      hour EC( 50) value in the range of 40.3%-63.0%). Similarly, out of seven dye
      industrial effluents, two were not acutely toxic and five minor acutely toxic.
      One of the two tanneries was moderately acutely toxic and another one was minor
      acutely toxic. Classification based on toxic unit revealed that four out of five
      pulp-paper effluent, three out of seven textile effluents, five out of seven dye
      effluents and both the tannery effluents were toxic. Overall, 66.67% effluents
      were found toxic and 33.33% as non-toxic. In general, tannery and dyes effluents
      showed more toxicity than textile and paper mill effluents.

PMID- 20823059
TI  - Neuromyelitis optica: a demyelinating disease characterized by acute destruction
      and regeneration of perivascular astrocytes.
AB  - BACKGROUND: A serum antibody directed against astrocytes is present in a high
      proportion of patients with neuromyelitis optica (NMO). The pathogenicity of the
      antibody is uncertain because no consistent astrocyte lesion is known to occur in
      NMO. OBJECTIVE: To determine whether there is an astrocyte lesion in NMO and if
      this differs from astrocyte changes in multiple sclerosis (MS). METHODS:
      Astrocyte pathology in early (still-myelinated) lesions and subacute NMO and MS
      lesions was examined immunohistochemically and in sections stained for astrocytes
      using routine histological techniques. RESULTS: Demyelination in early NMO
      lesions is accompanied by oligodendrocyte apoptosis in a pattern identical to
      that seen in MS and this is preceded by an abrupt destruction of perivascular
      astrocytes. Reparative astrogliosis is effected by a population of unipolar, new
      astrocytes. Evidence of a different type of astrocyte lesion was found in MS.
      DISCUSSION: The findings add to experimental evidence that the antibody is
      pathogenic. They also raise the possibility that demyelination in MS may be a
      bystander effect of an astrocyte lesion, i.e. that MS is not a disease primarily
      of myelin and oligodendrocytes.

PMID- 20823060
TI  - An interview with Ken Zaret. Interviewed by Kathryn Senior.

PMID- 20823061
TI  - KNOX genes: versatile regulators of plant development and diversity.
AB  - Knotted1-like homeobox (KNOX) proteins are homeodomain transcription factors that
      maintain an important pluripotent cell population called the shoot apical
      meristem, which generates the entire above-ground body of vascular plants. KNOX
      proteins regulate target genes that control hormone homeostasis in the meristem
      and interact with another subclass of homeodomain proteins called the BELL
      family. Studies in novel genetic systems, both at the base of the land plant
      phylogeny and in flowering plants, have uncovered novel roles for KNOX proteins
      in sculpting plant form and its diversity. Here, we discuss how KNOX proteins
      influence plant growth and development in a versatile context-dependent manner.

PMID- 20823062
TI  - A genome-wide screen in EpiSCs identifies Nr5a nuclear receptors as potent
      inducers of ground state pluripotency.
AB  - In rodents, the naive early epiblast undergoes profound morphogenetic,
      transcriptional and epigenetic changes after implantation. These differences are
      maintained between blastocyst-derived embryonic stem (ES) cells and egg cylinder
      derived epiblast stem cells (EpiSCs). Notably, ES cells robustly colonise
      chimaeras, whereas EpiSCs show little or no contribution. ES cells self-renew
      independently of mitogenic growth factors, whereas EpiSCs require fibroblast
      growth factor. However, EpiSCs retain the core pluripotency factors Oct4 and Sox2
      and the developmental barrier dividing them from unrestricted pluripotency can be
      surmounted by a single reprogramming factor. This provides an opportunity to
      identify molecules that can reset the naive state. We undertook a forward genetic
      screen for effectors of EpiSC reprogramming, employing piggyBac transposition to
      activate endogenous gene expression at random and selecting for undifferentiated
      colonies in the absence of growth factor signalling. Three recovered clones
      harboured integrations that activate the closely related orphan nuclear receptor
      genes Nr5a1 and Nr5a2. Activity of Nr5a1 and Nr5a2 was confirmed by direct
      transfection. Reprogrammed colonies were obtained without transgene integration
      and at 10-fold higher frequency than with other single factors. Converted cells
      exhibited the diagnostic self-renewal characteristics, gene expression profile
      and X chromosome activation signature of ground state pluripotency. They
      efficiently produced adult chimaeras and gave germline transmission. Nr5a
      receptors regulate Oct4 transcription but this is insufficient for reprogramming.
      Intriguingly, unlike previously identified reprogramming molecules, Nr5a
      receptors play no evident role in ES cell self-renewal. This implies a different
      foundation for their capacity to reset pluripotency and suggests that further
      factors remain to be identified.

PMID- 20823063
TI  - Glucose and aging control the quiescence period that follows pancreatic beta cell
      replication.
AB  - Pancreatic beta cell proliferation has emerged as the principal mechanism for
      homeostatic maintenance of beta cell mass during adult life. This underscores the
      importance of understanding the mechanisms of beta cell replication and suggests
      novel approaches for regenerative therapy to treat diabetes. Here we use an in
      vivo pulse-chase labeling assay to investigate the replication dynamics of adult
      mouse beta cells. We find that replicated beta cells are able to re-enter the
      cell division cycle shortly after mitosis and regain their normal proliferative
      potential after a short quiescence period of several days. This quiescence period
      is lengthened with advanced age, but shortened during injury-driven beta cell
      regeneration and following treatment with a pharmacological activator of
      glucokinase, providing strong evidence that metabolic demand is a key determinant
      of cell cycle re-entry. Lastly, we show that cyclin D2, a crucial factor in beta
      cell replication, is downregulated during cell division, and is slowly
      upregulated post-mitosis by a glucose-sensitive mechanism. These results
      demonstrate that beta cells quickly regain their capacity to re-enter the cell
      cycle post-mitosis and implicate glucose control of cyclin D2 expression in the
      regulation of this process.

PMID- 20823066
TI  - Clonal analysis reveals common lineage relationships between head muscles and
      second heart field derivatives in the mouse embryo.
AB  - Head muscle progenitors in pharyngeal mesoderm are present in close proximity to
      cells of the second heart field and show overlapping patterns of gene expression.
      However, it is not clear whether a single progenitor cell gives rise to both
      heart and head muscles. We now show that this is the case, using a retrospective
      clonal analysis in which an nlaacZ sequence, converted to functional nlacZ after
      a rare intragenic recombination event, is targeted to the alpha(c)-actin gene,
      expressed in all developing skeletal and cardiac muscle. We distinguish two
      branchiomeric head muscle lineages, which segregate early, both of which also
      contribute to myocardium. The first gives rise to the temporalis and masseter
      muscles, which derive from the first branchial arch, and also to the extraocular
      muscles, thus demonstrating a contribution from paraxial as well as prechordal
      mesoderm to this anterior muscle group. Unexpectedly, this first lineage also
      contributes to myocardium of the right ventricle. The second lineage gives rise
      to muscles of facial expression, which derive from mesoderm of the second
      branchial arch. It also contributes to outflow tract myocardium at the base of
      the arteries. Further sublineages distinguish myocardium at the base of the aorta
      or pulmonary trunk, with a clonal relationship to right or left head muscles,
      respectively. We thus establish a lineage tree, which we correlate with genetic
      regulation, and demonstrate a clonal relationship linking groups of head muscles
      to different parts of the heart, reflecting the posterior movement of the
      arterial pole during pharyngeal morphogenesis.

PMID- 20823064
TI  - Integrin-linked kinase regulates p38 MAPK-dependent cell cycle arrest in ureteric
      bud development.
AB  - The integrin-linked kinase (ILK), pinch and parvin ternary complex connects the
      cytoplasmic tails of beta1 integrins to the actin cytoskeleton. We recently
      showed that constitutive expression of ILK and alpha parvin in both the ureteric
      bud and the metanephric mesenchyme of the kidney is required for kidney
      development. In this study, we define the selective role of ILK in the ureteric
      bud of the mouse kidney in renal development by deleting it in the ureteric cell
      lineage before the onset of branching morphogenesis (E10.5). Although deleting
      ILK resulted in only a moderate decrease in branching, the mice died at 8 weeks
      of age from obstruction due to the unprecedented finding of intraluminal
      collecting duct cellular proliferation. ILK deletion in the ureteric bud resulted
      in the inability of collecting duct cells to undergo contact inhibition and to
      activate p38 mitogen-activated protein kinase (MAPK) in vivo and in vitro. p38
      MAPK activation was not dependent on the kinase activity of ILK. Thus, we
      conclude that ILK plays a crucial role in activating p38 MAPK, which regulates
      cell cycle arrest of epithelial cells in renal tubulogenesis.

PMID- 20823065
TI  - Plasma membrane-bound AGC3 kinases phosphorylate PIN auxin carriers at TPRXS(N/S)
      motifs to direct apical PIN recycling.
AB  - Polar membrane cargo delivery is crucial for establishing cell polarity and for
      directional transport processes. In plants, polar trafficking mediates the
      dynamic asymmetric distribution of PIN FORMED (PIN) carriers, which drive polar
      cell-to-cell transport of the hormone auxin, thereby generating auxin maxima and
      minima that control development. The Arabidopsis PINOID (PID) protein kinase
      instructs apical PIN localization by phosphorylating PINs. Here, we identified
      the PID homologs WAG1 and WAG2 as new PIN polarity regulators. We show that the
      AGC3 kinases PID, WAG1 and WAG2, and not other plant AGC kinases, instruct
      recruitment of PINs into the apical recycling pathway by phosphorylating the
      middle serine in three conserved TPRXS(N/S) motifs within the PIN central
      hydrophilic loop. Our results put forward a model by which apolarly localized
      PID, WAG1 and WAG2 phosphorylate PINs at the plasma membrane after default non
      polar PIN secretion, and trigger endocytosis-dependent apical PIN recycling. This
      phosphorylation-triggered apical PIN recycling competes with ARF-GEF GNOM
      dependent basal recycling to promote apical PIN localization. In planta,
      expression domains of PID, WAG1 and WAG2 correlate with apical localization of
      PINs in those cell types, indicating the importance of these kinases for apical
      PIN localization. Our data show that by directing polar PIN localization and PIN
      mediated polar auxin transport, the three AGC3 kinases redundantly regulate
      cotyledon development, root meristem size and gravitropic response, indicating
      their involvement in both programmed and adaptive plant development.

PMID- 20823067
TI  - Anterior neural development requires Del1, a matrix-associated protein that
      attenuates canonical Wnt signaling via the Ror2 pathway.
AB  - During early embryogenesis, the neural plate is specified along the anterior
      posterior (AP) axis by the action of graded patterning signals. In particular,
      the attenuation of canonical Wnt signals plays a central role in the
      determination of the anterior brain region. Here, we show that the extracellular
      matrix (ECM) protein Del1, expressed in the anterior neural plate, is essential
      for forebrain development in the Xenopus embryo. Overexpression of Del1 expands
      the forebrain domain and promotes the formation of head structures, such as the
      eye, in a Chordin-induced secondary axis. Conversely, the inhibition of Del1
      function by a morpholino oligonucleotide (MO) represses forebrain development.
      Del1 also augments the expression of forebrain markers in neuralized animal cap
      cells, whereas Del1-MO suppresses them. We previously reported that Del1
      interferes with BMP signaling in the dorsal-ventral patterning of the gastrula
      marginal zone. By contrast, we demonstrate here that Del1 function in AP neural
      patterning is mediated mainly by the inhibition of canonical Wnt signaling. Wnt
      induced posteriorization of the neural plate is counteracted by Del1, and the
      Del1-MO phenotype (posteriorization) is reversed by Dkk1. Topflash reporter
      assays show that Del1 suppresses luciferase activities induced by Wnt1 and beta
      catenin. This inhibitory effect of Del1 on canonical Wnt signaling, but not on
      BMP signaling, requires the Ror2 pathway, which is implicated in non-canonical
      Wnt signaling. These findings indicate that the ECM protein Del1 promotes
      forebrain development by creating a local environment that attenuates the
      cellular response to posteriorizing Wnt signals via a unique pathway.

PMID- 20823068
TI  - SPAT-1/Bora acts with Polo-like kinase 1 to regulate PAR polarity and cell cycle
      progression.
AB  - During asymmetric cell division, cell polarity and cell cycle progression are
      tightly coordinated, yet mechanisms controlling both these events are poorly
      understood. Here we show that the Bora homologue SPAT-1 regulates both PAR
      polarity and cell cycle progression in C. elegans embryos. We find that,
      similarly to mammalian cells, SPAT-1 acts with PLK-1 and not with the mitotic
      kinase Aurora A (AIR-1), as shown in Drosophila. SPAT-1 binds to PLK-1, and
      depletion of SPAT-1 or PLK-1 leads to similar cell division defects in early
      embryos, which differ from the defects caused by depletion of AIR-1.
      Additionally, SPAT-1 and PLK-1 depletion causes impaired polarity with abnormal
      length of the anterior and posterior PAR domains, and partial plk-1(RNAi) or spat
      1(RNAi), but not air-1(RNAi), can rescue the lethality of a par-2 mutant. SPAT-1
      is enriched in posterior cells, and this enrichment depends on PAR polarity and
      PLK-1. Taken together, our data suggest a model in which SPAT-1 promotes the
      activity of PLK-1 to regulate both cell polarity and cell cycle timing during
      asymmetric cell division, providing a link between these two processes.

PMID- 20823069
TI  - A genetic cascade involving klumpfuss, nab and castor specifies the abdominal
      leucokinergic neurons in the Drosophila CNS.
AB  - Identification of the genetic mechanisms underlying the specification of large
      numbers of different neuronal cell fates from limited numbers of progenitor cells
      is at the forefront of developmental neurobiology. In Drosophila, the identities
      of the different neuronal progenitor cells, the neuroblasts, are specified by a
      combination of spatial cues. These cues are integrated with temporal competence
      transitions within each neuroblast to give rise to a specific repertoire of cell
      types within each lineage. However, the nature of this integration is poorly
      understood. To begin addressing this issue, we analyze the specification of a
      small set of peptidergic cells: the abdominal leucokinergic neurons. We identify
      the progenitors of these neurons, the temporal window in which they are specified
      and the influence of the Notch signaling pathway on their specification. We also
      show that the products of the genes klumpfuss, nab and castor play important
      roles in their specification via a genetic cascade.

PMID- 20823070
TI  - Extracellular control of PAR protein localization during asymmetric cell division
      in the C. elegans embryo.
AB  - The axis of asymmetric cell division is controlled to determine the future
      position of differentiated cells during animal development. The asymmetric
      localization of PAR proteins in the Drosophila neuroblast and C. elegans embryo
      are aligned with the axes of the embryo. However, whether extracellular or
      intracellular signals determine the orientation of the localization of PAR
      proteins remains controversial. In C. elegans, the P0 zygote and germline cells
      (P1, P2, and P3) undergo a series of asymmetric cell divisions. Interestingly,
      the axis of the P0 and P1 divisions is opposite to that of the P2 and P3
      divisions. PAR-2, a ring-finger protein, and PAR-1, a kinase, relocalize to the
      anterior side of the P2 and P3 germline precursors at the site of contact with
      endodermal precursors. Using an in vitro method, we have found that the PAR-2
      protein is distributed asymmetrically in the absence of extracellular signals,
      but the orientation of the protein localization in the P2 and P3 cells is
      determined by contact with endodermal precursor cells. Our mutant analyses
      suggest that mes-1 and src-1, which respectively encode a transmembrane protein
      and a tyrosine kinase, were not required to establish the asymmetric distribution
      of PAR-2, but were required to determine its orientation at the site of contact
      with the endodermal precursors. The PAR-2 localization during the asymmetric P2
      and P3 divisions is controlled by extracellular signals via MES-1/SRC-1
      signaling. Our findings suggest that Src functions as an evolutionarily conserved
      molecular link that coordinates extrinsic cues with PAR protein localization.

PMID- 20823071
TI  - Why do women use intimate partner violence? A systematic review of women's
      motivations.
AB  - Studies report that women use as much or more physical intimate partner violence
      (IPV) as men. Most of these studies measure IPV by counting the number of IPV
      acts over a specified time period, but counting acts captures only one aspect of
      this complex phenomenon. To inform interventions, women's motivations for using
      IPV must be understood. A systematic review, therefore, was conducted to
      summarize evidence regarding women's motivations for the use of physical IPV in
      heterosexual relationships. Four published literature databases were searched,
      and articles that met inclusion criteria were abstracted. This was supplemented
      with a bibliography search and expert consultation. Eligible studies included
      English-language publications that directly investigated heterosexual women's
      motivations for perpetrating nonlethal, physical IPV. Of the 144 potentially
      eligible articles, 23 met inclusion criteria. Over two thirds of studies enrolled
      participants from IPV shelters, courts, or batterers' treatment programs. Women's
      motivations were primarily assessed through interviews or administration of an
      author-created questionnaire. Anger and not being able to get a partner's
      attention were pervasive themes. Self-defense and retaliation also were commonly
      cited motivations, but distinguishing the two was difficult in some studies.
      Control was mentioned but not listed as a primary motivation. IPV prevention and
      treatment programs should explore ways to effectively address women's
      relationship concerns and ability to manage anger and should recognize that women
      commonly use IPV in response to their partner's violence.

PMID- 20823072
TI  - Psychological trauma and substance abuse: the need for an integrated approach.
AB  - There is consensus that an integrated approach which addresses the clinical needs
      of individuals who have histories of substance abuse and psychological trauma
      concurrently is an acceptable and preferred approach to treatment. Several
      integrated models have emerged in recent years. In this paper we first define the
      concepts of substance abuse and psychological trauma, investigate the
      relationship between both and proceed to discuss why an integrated approach is
      most compelling. Finally, we review and critically examine the different
      integrated models that have been developed in terms of efficacy, effectiveness
      and empirical evidence. The paper concludes with suggestions on how the field can
      be improved.

PMID- 20823073
TI  - Should the size threshold for elective abdominal aortic aneurysm repair be
      lowered in the endovascular era? Yes.
AB  - According to current international guidelines, patients with infrarenal or
      juxtarenal abdominal aortic aneurysms (AAAs) measuring > or = 5.5 cm should
      undergo repair to reduce the risk of rupture. The 5.5-cm-diameter threshold is
      the size when the AAA rupture rate balances the mortality rates of elective open
      surgical AAA repair (3%). Endovascular AAA repair (EVAR) is associated with lower
      perioperative mortality and complication rates compared with open surgical
      repair. This debate addresses the issue whether the current size threshold for
      elective AAA repair needs to be lowered in the endovascular era. This paper
      supports the position that the size threshold for AAA repair should be lowered in
      the endovascular era.

PMID- 20823074
TI  - Should the size threshold for elective abdominal aortic aneurysm repair be
      lowered in the endovascular era? No.
AB  - According to the current international guidelines, patients with infrarenal or
      juxtarenal abdominal aortic aneurysms (AAAs) measuring > or = 5.5 cm should
      undergo repair to reduce the risk of rupture. The 5.5-cm-diameter threshold is
      the size when the AAA rupture rate balances the mortality rates of elective open
      surgical AAA repair (3%). Endovascular AAA repair (EVAR) is associated with lower
      perioperative mortality and complication rates compared with open surgical
      repair. This debate addresses the issue whether the current size threshold for
      elective AAA repair needs to be lowered in the endovascular era. This article
      supports the position that the size threshold for AAA repair should not be
      lowered.

PMID- 20823076
TI  - Do excessive internet use, television viewing and poor lifestyle habits affect
      low vision in school children?
AB  - The aim of this study is to determine whether excessive internet use, television
      viewing and the ensuing poor lifestyle habits affect low vision in school
      children in a rapidly developing country. This is a cross-sectional study and
      3000 school students aged between six and 18 years were approached and 2467
      (82.2%) students participated. Of the studied school children 12.6 percent had
      low vision. Most of the low vision school children were in the 6-10 years age
      group and came from middle income backgrounds (41.8%; p = 0.008). A large
      proportion of the children with low vision spent >= 3 hours per day on the
      internet (48.2%; p< 0.001) and >= 3 hours reclining (62.4%; p < 0.001). A
      significantly smaller frequency of studied children with low vision participated
      in each of the reviewed forms of physical activity (p < 0.001) yet a larger
      proportion consumed fast food (86.8%; p < 0.001). Highly significant positive
      correlations were found between low vision and BMI, hours spent reclining and on
      the internet respectively. Blurred vision was the most commonly complained of
      symptom among the studied children (p < 0.001). The current study suggested a
      strong association between spending prolonged hours on the computer or TV, fast
      food eating, poor lifestyle habits and low vision.

PMID- 20823075
TI  - Analysis of the microbiota of sputum samples from patients with lower respiratory
      tract infections.
AB  - Sputum is the most common sample collected from patients suffering from lower
      respiratory tract infections and it is crucial for the bacterial identification
      of these infections. In this study, we enrolled 101 sputum samples from 101
      patients with lower respiratory tract infections. Initially, pyrosequencing of
      the 16S rDNA V3 hypervariable regions of the bacteria contained in the sputum was
      utilized as a culture-independent approach for microbiota analysis. For
      comparison, clinical laboratory tests using a culture-dependent automated
      bacterial identification system for the same cohort of sputum samples were also
      done. By pyrosequencing, >70,000 DNA fragments were found and classified into 129
      bacterial genera after being analyzed by the Ribosomal Database Project (RDP)
      process. Most sequences belonged to several predominant genera, such as
      Streptococcus and Staphylococcus, indicating that these genera play an important
      role in lower respiratory tract infections. In addition, some sequences belonging
      to potential causative agents, such as Mycoplasma, Haemophilus, and Moraxella,
      were also found, but these sequences were not found by clinical laboratory tests.
      For the nine genera detected by both methods, the methods' sensitivities were
      compared and the results showed that pyrosequencing was more sensitive, except
      for Klebsiella and Mycobacterium. Significantly, this method revealed much more
      complicated bacterial communities and it showed a promising ability for the
      detection of bacteria.

PMID- 20823077
TI  - Ethical dilemmas before and during anaesthetic induction of young children, as
      described by nurse anaesthetists.
AB  - Research on physicians', nurses' and enrolled nurses' experiences of ethical
      dilemmas have been conducted in many healthcare fields. The aim of this study was
      to elucidate ethical dilemmas before and during the induction of anaesthesia of
      children aged three to six years as described by nurse anaesthetists (NAs). Two
      group interviews with NAs were conducted where they were asked to describe
      ethically problematic situations. Three situations were chosen from a total of
      15: administration of anaesthesia to an already sleeping child, lack of
      information given to a child, and a child is anaesthetized against his/her will.
      Conceivable and reasonable alternative options were identified and consequences
      of the different actions were presented. Finally the conflicts of value were
      discussed and commented on. The cases describe when a child's rights are given
      less weight and the child has little opportunity to participate in the decision
      making. However, parents and NAs acted in the best interest of the child.
      Analysing and reflecting on situations involving ethical dilemmas would enhance
      NAs critical thinking and guide NAs in their decision making when providing
      anaesthesia care.

PMID- 20823078
TI  - Containing acute childhood illness within family life: a substantive grounded
      theory.
AB  - Acute childhood illness is a universal experience for children and families. This
      paper presents the central process of a Glaserian grounded theory study which
      explored family management of acute childhood illness at home. Twenty-nine
      interviews were conducted with 15 families of children 0-9 years of age. Constant
      comparative analysis generated the substantive grounded theory 'Containing acute
      childhood illness within family life'. This informal social rule was identified
      from families' persistent desire to do the right thing, for their child and in
      the eyes of others in social life. Families perceived that they were expected to
      contain illnesses which are defined as minor and to seek medical help for 'real'
      illnesses. Considerable uncertainty was evident around defining the illness and
      the legitimacy of seeking medical help. Their concern with the latter indicates
      doctors' role as moral agents for parents' behaviour, directing the containment
      of acute childhood illness.

PMID- 20823079
TI  - Scopolamine disrupts hippocampal activity during allocentric spatial memory in
      humans: an fMRI study using a virtual reality analogue of the Morris Water Maze.
AB  - The role of the septohippocampal cholinergic system in memory disorders is well
      established. The effects of cholinergic challenge in animals have been
      extensively studied using the Morris Water Maze (MWM) which engages allocentric
      spatial memory. The present study investigated the effect of the centrally active
      muscarinic antagonist scopolamine on allocentric spatial memory in humans using a
      virtual reality analogue of the MWM task, the Arena task. Twenty right-handed
      healthy male adults with a mean age of 28 years (range 23-35 years) were studied
      using functional MRI in a randomized double-blind cross-over design with
      scopolamine bromide (0.4 mg i.m.) or placebo (saline) administered 70-90 min
      before the beginning of the functional scan. Scopolamine induced a significant
      reduction in the activation of the hippocampus/parahippocampal gyrus compared
      with placebo. Furthermore, there was dissociation between hippocampus-based and
      striatal-based memory systems, which were significantly more activated in the
      placebo and scopolamine conditions, respectively. The activation of the striatal
      system under scopolamine challenge was accompanied by the activation of the
      amygdala. In conclusion, the study extends the well-documented finding in animals
      of the attenuating effect of scopolamine on hippocampal activity during
      allocentric spatial memory to humans. Furthermore, the results call for further
      investigation of the dissociation between the hippocampal and neostriatal memory
      systems during allocentric spatial processing under cholinergic blockade in
      humans.

PMID- 20823080
TI  - Lamotrigine: when and where does it act in affective disorders? A systematic
      review.
AB  - Recent published data and treatment guidelines have created uncertainty about the
      use of lamotrigine in affective disorders, especially in acute bipolar
      depression. Furthermore, unpublished data on lamotrigine in mania, mixed
      episodes, unipolar depression and rapid cycling are still waiting to be
      integrated into the literature. Therefore, we critically reviewed the position of
      lamotrigine in the acute and long-term treatment of affective disorders. Studies
      were identified by searching English language articles published in MEDLINE using
      the key words: lamotrigine, bipolar depression, unipolar depression, mania, mixed
      episode, long-term treatment, rapid-cycling. Results of unpublished trials were
      obtained from the GlaxoSmithKline website. Lamotrigine showed efficacy in the
      prophylaxis of bipolar disorder, more so in depressive than manic episodes. There
      was no evidence of effectiveness in the acute treatment of mania, mixed episodes,
      unipolar depression or rapid-cycling bipolar I disorder. Its effect in the acute
      treatment of bipolar depression is at most small. Based on current evidence,
      lamotrigine is indicated for the prophylaxis of bipolar disorder with
      predominantly depressive episodes. Its effectiveness in the acute treatment of
      bipolar depression is open to debate, and practical considerations limit its
      usefulness here. There are no grounds for recommending its use in manic or mixed
      states, in rapidly-cycling bipolar I or in unipolar depression.

PMID- 20823081
TI  - Lower vitamin D levels are associated with depression among community-dwelling
      European men.
AB  - Low serum 25-hydroxyvitamin D (25(OH)D) and elevated parathyroid hormone (PTH)
      levels have been linked with depressive symptoms among adults in various clinical
      settings. Data in generally healthy, community-dwelling individuals remain
      inconclusive. We investigated whether depression was associated with 25(OH)D
      and/or PTH in a sample of middle-aged and older men (n = 3369; mean age 60 +/-
      11) participating in the European Male Ageing Study, and whether any associations
      were explained by lifestyle and health factors. The Beck Depression Inventory-II
      (BDI-II) was used to screen for depression, and serum 25(OH)D and PTH levels
      measured by radioimmunoassay. Univariate analysis revealed that 25(OH)D levels
      were lower (p < 0.001) and PTH higher (p = 0.004) in people with depression. In
      age- and centre-adjusted linear regressions a higher BDI-II score was
      significantly associated with lower levels of 25(OH)D (p = 0.004). After
      adjustment for lifestyle and health factors this relationship was attenuated but
      remained significant (p = 0.01). Using multivariable logistic regression the odds
      for depression increased approximately 70% across decreasing 25(OH)D quartiles (p
      (trend) = 0.04). There was no independent association between PTH and depression
      in any of the multivariable regressions. Our results reveal an inverse
      association between 25(OH)D levels and depression, largely independent of several
      lifestyle and health factors. Further studies are required to determine whether
      higher levels of vitamin D have an antidepressant effect in older adults.

PMID- 20823082
TI  - The bioinformatics of next generation sequencing: a meeting report.

PMID- 20823083
TI  - Partial reversal of the methylation pattern of the X-linked gene HUMARA during
      hematopoietic differentiation of human embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) can be induced to differentiate towards
      hematopoiesis with high efficiency. In this work, we analyzed the methylation
      status of the X-linked HUMARA (human androgen receptor) gene in hematopoietic
      cells derived from hESC line H9 before and after induction of hematopoietic
      differentiation. All passages of H9 and H9-derived hematopoietic cells displayed
      homogenous methylation pattern with disappearance of the same allele upon HpaII
      digestion. This pattern persisted in the great majority of different
      hematopoietic progenitors derived from H9, except in 11 of 86 individually
      plucked colonies in which an equal digestion of the HUMARA alleles has been
      found, suggesting that a methylation change occurring at this locus during
      differentiation. Interestingly, quantification of X inactive-specific transcript
      (XIST) RNA in undifferentiated H9 cell line and day 14 embryoid bodies (EB) by RT
      PCR did not show any evidence of XIST expression either before or after
      differentiation. Thus, during self-renewal conditions and after induction of
      commitment towards the formation of EB, the methylation pattern of the HUMARA
      locus appears locked with the same unmethylated allele. However, hematopoietic
      differentiation seems to be permissive to the reversal of methylation status of
      HUMARA in some terminally differentiated progenitors. These data suggest that
      monitoring methylation of HUMARA gene during induced differentiation could be of
      use for studying hESC-derived hematopoiesis.

PMID- 20823084
TI  - Implicit awareness in anosognosia for hemiplegia: unconscious interference
      without conscious re-representation.
AB  - Some patients with anosognosia for hemiplegia, i.e. apparent unawareness of
      hemiplegia, have been clinically observed to show 'tacit' or 'implicit' awareness
      of their deficits. Here we have experimentally examined whether implicit and
      explicit responses to the same deficit-related material can dissociate. Fourteen
      stroke patients with right hemisphere lesions and contralesional paralysis were
      tested for implicit and explicit responses to brief sentences with deficit
      related themes. These responses were elicited using: (i) a verbal inhibition test
      in which patients had to inhibit completing each sentence with an automatic
      response (implicit task) and (ii) a rating procedure in which patients rated the
      self-relevance of the same sentences (explicit task). A group of anosognosic
      hemiplegic patients was significantly slower than a control group of aware
      hemiplegic patients in performing the inhibition task with deficit-related
      sentences than with other emotionally negative themes (relative to neutral
      themes). This occurred despite their explicit denial of the self-relevance of the
      former sentences. Individual patient analysis showed that six of the seven
      anosognosic patients significantly differed from the control group in this
      dissociation. Using lesion mapping procedures, we found that the lesions of the
      anosognosic patients differed from those of the 'aware' controls mainly by
      involving the anterior parts of the insula, inferior motor areas, basal ganglia
      structures, limbic structures and deep white matter. In contrast, the anosognosic
      patient without implicit awareness had more cortical lesions, mostly in frontal
      areas, including lateral premotor regions, and also in the parietal and occipital
      lobes. These results provide strong experimental support for a specific
      dissociation between implicit and explicit awareness of deficits. More generally,
      the combination of our behavioural and neural findings suggests that an explicit,
      affectively personalized sensorimotor awareness requires the re-representation of
      sensorimotor information in the insular cortex, with possible involvement of
      limbic areas and basal ganglia circuits. The delusional features of anosognosia
      for hemiplegia can be explained as a failure of this re-representation.

PMID- 20823085
TI  - Brain activation during cognitive planning in twins discordant or concordant for
      obsessive-compulsive symptoms.
AB  - Neuroimaging studies have indicated abnormalities in cortico-striatal-thalamo
      cortical circuits in patients with obsessive-compulsive disorder compared with
      controls. However, there are inconsistencies between studies regarding the exact
      set of brain structures involved and the direction of anatomical and functional
      changes. These inconsistencies may reflect the differential impact of
      environmental and genetic risk factors for obsessive-compulsive disorder on
      different parts of the brain. To distinguish between functional brain changes
      underlying environmentally and genetically mediated obsessive-compulsive
      disorder, we compared task performance and brain activation during a Tower of
      London planning paradigm in monozygotic twins discordant (n=38) or concordant
      (n=100) for obsessive-compulsive symptoms. Twins who score high on obsessive
      compulsive symptoms can be considered at high risk for obsessive-compulsive
      disorder. We found that subjects at high risk for obsessive-compulsive disorder
      did not differ from the low-risk subjects behaviourally, but we obtained evidence
      that the high-risk subjects differed from the low-risk subjects in the patterns
      of brain activation accompanying task execution. These regions can be separated
      into those that were affected by mainly environmental risk (dorsolateral
      prefrontal cortex and lingual cortex), genetic risk (frontopolar cortex, inferior
      frontal cortex, globus pallidus and caudate nucleus) and regions affected by both
      environmental and genetic risk factors (cingulate cortex, premotor cortex and
      parts of the parietal cortex). Our results suggest that neurobiological changes
      related to obsessive-compulsive symptoms induced by environmental factors involve
      primarily the dorsolateral prefrontal cortex, whereas neurobiological changes
      induced by genetic factors involve orbitofrontal-basal ganglia structures.
      Regions showing similar changes in high-risk twins from discordant and concordant
      pairs may be part of compensatory networks that keep planning performance intact,
      in spite of cortico-striatal-thalamo-cortical deficits.

PMID- 20823086
TI  - Agent strain variation in human prion disease: insights from a molecular and
      pathological review of the National Institutes of Health series of experimentally
      transmitted disease.
AB  - Six clinico-pathological phenotypes of sporadic Creutzfeldt-Jakob disease have
      been characterized which correlate at the molecular level with the type (1 or 2)
      of the abnormal prion protein, PrP(TSE), present in the brain and with the
      genotype of polymorphic (methionine or valine) codon 129 of the prion protein
      gene. However, to what extent these phenotypes with their corresponding molecular
      combinations (i.e. MM1, MM2, VV1 etc.) encipher distinct prion strains upon
      transmission remains uncertain. We studied the PrP(TSE) type and the prion
      protein gene in archival brain tissues from the National Institutes of Health
      series of transmitted Creutzfeldt-Jakob disease and kuru cases, and characterized
      the molecular and pathological phenotype in the affected non-human primates,
      including squirrel, spider, capuchin and African green monkeys. We found that the
      transmission properties of prions from the common sporadic Creutzfeldt-Jakob
      disease MM1 phenotype are homogeneous and significantly differ from those of
      sporadic Creutzfeldt-Jakob disease VV2 or MV2 prions. Animals injected with
      iatrogenic Creutzfeldt-Jakob disease MM1 and genetic Creutzfeldt-Jakob disease
      MM1 linked to the E200K mutation showed the same phenotypic features as those
      infected with sporadic Creutzfeldt-Jakob disease MM1 prions, whereas kuru most
      closely resembled the sporadic Creutzfeldt-Jakob disease VV2 or MV2 prion
      signature and neuropathology. The findings indicate that two distinct prion
      strains are linked to the three most common Creutzfeldt-Jakob disease clinico
      pathological and molecular subtypes and kuru, and suggest that kuru may have
      originated from cannibalistic transmission of a sporadic Creutzfeldt-Jakob
      disease of the VV2 or MV2 subtype.

PMID- 20823087
TI  - Relationship of dementia screening tests with biomarkers of Alzheimer's disease.
AB  - Screening tests for Alzheimer's disease lack sensitivity and specificity. We
      developed the AD8, a brief dementia screening interview validated against
      clinical and cognitive evaluations, as an improvement over current screening
      methods. Because insufficient follow-up has occurred to validate the AD8 against
      the neuropathologic findings of Alzheimer's disease, we investigated whether AD8
      scores correspond to impairment in episodic memory testing and changes in
      biomarkers of Alzheimer's disease (cerebrospinal fluid and amyloid imaging with
      Pittsburgh compound B) characteristic of symptomatic Alzheimer's disease. We also
      compared informant-based assessments with brief performance-based dementia
      screening measurements such as the Mini Mental State Exam. The sample (n = 257)
      had a mean age of 75.4 years with 15.1 years of education; 88.7% were Caucasian
      and 45.5% were male. The sample was divided into two groups based on their AD8
      scores: those with a negative dementia screening test (AD8 score 0 or 1, n = 137)
      and those with a positive dementia screening test (AD8 score >=2, n = 120).
      Individuals with positive AD8 scores had abnormal Pittsburgh compound B binding
      (P < 0.001) and cerebrospinal fluid biomarkers (P < 0.001) compared with
      individuals with negative AD8 scores. Individuals with positive AD8 tests and
      positive biomarkers scored in the impaired range on the Wechsler Logical Memory
      Story A (mean score 7.0 +/- 4.5 for Pittsburgh compound B; mean score 7.6 +/- 5.3
      for cerebrospinal fluid amyloid beta protein 1-42). The AD8 area under the curve
      for Pittsburgh compound B was 0.737 (95% confidence interval: 0.64-0.83) and for
      cerebrospinal fluid amyloid beta protein 1-42 was 0.685 (95% confidence interval:
      0.60-0.77) suggesting good discrimination. The AD8 had superior sensitivity in
      detecting early stages of dementia compared with the Mini Mental State
      Examination. The AD8 had a likelihood ratio of a positive test of 5.8 (95%
      confidence interval: 5.4-6.3) and likelihood ratio of a negative test of 0.04
      (95% confidence interval: 0.03-0.06), increasing the pre-test probability of an
      individual having symptomatic Alzheimer's disease. Individuals with AD8 scores of
      >=2 had a biomarker phenotype consistent with Alzheimer's disease and lower
      performance on episodic memory tests, supporting a diagnosis of Alzheimer's
      disease. Informant-based assessments may be superior to performance-based
      screening measures such as the Mini Mental State Examination in corresponding to
      underlying Alzheimer's disease pathology, particularly at the earliest stages of
      decline. The use of a brief test such as the AD8 may improve strategies for
      detecting dementia in community settings where biomarkers may not be readily
      available, and may enrich clinical trial recruitment by increasing the likelihood
      that participants have underlying biomarker abnormalities.

PMID- 20823088
TI  - Predictors of long-term anti-retroviral therapy effectiveness among Brazilian HIV
      1-infected children in a hybrid scenario: what really matters?
AB  - The study objective was to evaluate the effectiveness and durability of highly
      active anti-retroviral therapy (HAART) in perinatally HIV-1-infected children and
      adolescents and its predictors. A historical cohort study was done at IMIP's
      Hospital in Recife, Brazil. The study included 195 subjects, 102 (52.3%) had
      successful response to HAART with a mean time of any HAART use of 4.9 [standard
      deviation (SD) 2.5; min. 0.7, max. 9.9] years. The time to failure of first HAART
      was negatively associated with male sex [relative hazard (RH) = 0.5, p = 0.021)
      and living out of metropolitan area (RH = 0.4, p = 0.009), and associated with
      Centres for Diseases Control and Prevention (CDC) immunological Stage 1 (RH =
      2.9, p = 0.003) and patients who were adherent (RH = 2.2, p = 0.003). HAART
      success rate and mean time durability was similar to developed country data.
      However, the main predictors of success were: female sex, living in a
      metropolitan area, CDC1 immunological category and adherence.

PMID- 20823089
TI  - Pre-exchange 5% albumin infusion in low birth weight neonates with intensive
      phototherapy failure--a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the role of 5% albumin infusion before exchange
      transfusion in reducing post-exchange unconjugated serum bilirubin (UCB) levels
      in low birth weight (LBW) neonates with intensive phototherapy failure. METHODS:
      In a placebo-controlled Randomized Controlled Trial, 42 healthy LBW (birth weight
      between 1000 and 2499 g and gestational age >= 32 weeks) neonates were randomly
      allocated into intervention and control groups. Post-exchange UCB at 6 and 12 h
      were compared in the two groups along with the duration of post-exchange
      phototherapy, repeat-exchange requirement, adverse effects of albumin and
      hospital stay. RESULTS: The intervention group (n = 21) with mean birth weight
      1619 +/- 324 g, gestational age 34.5 +/- 1.65 weeks, peak UCB 19 +/- 3.85 mg dl(
      1), was demographically comparable with the control group (n = 21) (1660 +/- 320
      g, 34 +/- 1.6 weeks, 19.4 +/- 3.59 mg dl(-1), respectively). Significant
      reduction in the post-exchange UCB (10.55 +/- 1.53 mg dl(-1) at 6 h; 5.86 +/-
      1.21 mg dl(-1) at 12 h in albumin group; 15.26 +/- 1.78 mg dl(-1) at 6 h; 11.69
      +/- 1.52 mg dl(-1) at 12 h in control group) and phototherapy duration (23.8 +/-
      3.2 h vs. 40.3 +/- 7.2 h) was observed in the intervention group (p < 0.0001).
      Repeat exchange requirement was reduced by 86% (RR = 0.14; 95%CI: 0.19-1.06).
      Mean duration of hospital stay was significantly lower (10.1 +/- 5.8 days vs.
      12.4 +/- 6.6 days) (p = 0.021). No albumin transfusion-related complications were
      observed.

PMID- 20823090
TI  - Allotopic expression of mitochondrial-encoded genes in mammals: achieved goal,
      undemonstrated mechanism or impossible task?
AB  - Mitochondrial-DNA diseases have no effective treatments. Allotopic expression
      synthesis of a wild-type version of the mutated protein in the nuclear-cytosolic
      compartment and its importation into mitochondria-has been proposed as a gene
      therapy approach. Allotopic expression has been successfully demonstrated in
      yeast, but in mammalian mitochondria results are contradictory. The evidence
      available is based on partial phenotype rescue, not on the incorporation of a
      functional protein into mitochondria. Here, we show that reliance on partial
      rescue alone can lead to a false conclusion of successful allotopic expression.
      We recoded mitochondrial mt-Nd6 to the universal genetic code, and added the N
      terminal mitochondrial-targeting sequence of cytochrome c oxidase VIII (C8) and
      the HA epitope (C8Nd6HA). The protein apparently co-localized with mitochondria,
      but a significant part of it seemed to be located outside mitochondria. Complex I
      activity and assembly was restored, suggesting successful allotopic expression.
      However, careful examination of transfected cells showed that the allotopically
      expressed protein was not internalized in mitochondria and that the selected
      clones were in fact revertants for the mt-Nd6 mutation. These findings
      demonstrate the need for extreme caution in the interpretation of functional
      rescue experiments and for clear-cut controls to demonstrate true rescue of
      mitochondrial function by allotopic expression.

PMID- 20823091
TI  - The many paths to frameshifting: kinetic modelling and analysis of the effects of
      different elongation steps on programmed -1 ribosomal frameshifting.
AB  - Several important viruses including the human immunodeficiency virus type 1 (HIV
      1) and the SARS-associated Coronavirus (SARS-CoV) employ programmed -1 ribosomal
      frameshifting (PRF) for their protein expression. Here, a kinetic framework is
      developed to describe -1 PRF. The model reveals three kinetic pathways to -1 PRF
      that yield two possible frameshift products: those incorporating zero frame
      encoded A-site tRNAs in the recoding site, and products incorporating -1 frame
      encoded A-site tRNAs. Using known kinetic rate constants, the individual
      contributions of different steps of the translation elongation cycle to -1 PRF
      and the ratio between two types of frameshift products were evaluated. A dual
      fluorescence reporter was employed in Escherichia coli to empirically test the
      model. Additionally, the study applied a novel mass spectrometry approach to
      quantify the ratios of the two frameshift products. A more detailed understanding
      of the mechanisms underlying -1 PRF may provide insight into developing antiviral
      therapeutics.

PMID- 20823092
TI  - Bone marrow lesions in people with knee osteoarthritis predict progression of
      disease and joint replacement: a longitudinal study.
AB  - OBJECTIVES: The presence of bone marrow lesions (BMLs) has been linked to pain
      and progression of knee OA. The aim of this study was to determine the
      relationship between BMLs and longitudinal change in tibial cartilage volume and
      risk of knee joint replacement in subjects with knee OA. METHODS: One hundred and
      nine men and women with symptomatic knee OA were recruited. The same knee was
      imaged using MRI at baseline and ~2 years later. Tibial cartilage volume and BMLs
      were measured. Knee joint replacement over 4 years was determined. RESULTS: The
      mean age of the subjects at baseline was 63.2 (s.d. 10.3) years. BMLs were
      present in 66% of the subjects. Cross-sectionally, BMLs were negatively
      associated with both medial (regression coefficient -121.4; 95% CI -183.8, 
      859.1; P<0.001) and lateral (regression coefficient -142.1; 95% CI -241.8, -42.4;
      P=0.01) tibial cartilage volume data. Longitudinally, for every 1-score increase
      in baseline BML severity (range 0-4), the annual total tibial cartilage loss was
      increased by 1.14% (95% CI 0.29%, 1.87%; P=0.01). The risk of knee joint
      replacement over 4 years increased with increasing BML score (odds ratio 1.57;
      95% CI 1.04, 2.35; P=0.03). CONCLUSION: The prevalence and severity of BMLs are
      associated with less tibial cartilage volume and greater cartilage loss over 2
      years. Moreover, severity of BMLs was positively associated with risk of knee
      joint replacement over 4 years. This provides further support for the importance
      of BMLs in identifying those with OA most likely to progress. Identifying factors
      that prevent or reduce the severity of BMLs may provide an important target in
      the prevention of disease progression and treatment of OA, and the subsequent
      need for arthroplasty.

PMID- 20823093
TI  - The management of peripheral blood cytopenias in systemic lupus erythematosus.
AB  - Haematological complications are frequently seen in SLE. Anaemia, leucopenias and
      thrombocytopenia may result from bone marrow failure or excessive peripheral cell
      destruction, both of which may be immune mediated. Drugs and infection are other
      common causes. In this review, we will focus on the diagnosis and management of
      immune-mediated leucopenias and thrombocytopenia in SLE. The roles of bone marrow
      examination and the measurement of antibodies against leucocytes and platelets
      are discussed. Although many patients do not require specific treatment for
      cytopenias in SLE, CSs remain the mainstay of treatment. Other conventional
      therapies include AZA, CYC and human normal immunoglobulin. More recently, MMF
      has found a role as a CS and CYC-sparing agent. We also review B-cell depletion
      in the management of thrombocytopenia associated with SLE and other novel
      therapies including thrombopoeitin receptor agonists.

PMID- 20823094
TI  - A national registry for juvenile dermatomyositis and other paediatric idiopathic
      inflammatory myopathies: 10 years' experience; the Juvenile Dermatomyositis
      National (UK and Ireland) Cohort Biomarker Study and Repository for Idiopathic
      Inflammatory Myopathies.
AB  - OBJECTIVES: The paediatric idiopathic inflammatory myopathies (IIMs) are a group
      of rare chronic inflammatory disorders of childhood, affecting muscle, skin and
      other organs. There is a severe lack of evidence base for current treatment
      protocols in juvenile myositis. The rarity of these conditions means that
      multicentre collaboration is vital to facilitate studies of pathogenesis,
      treatment and disease outcomes. We have established a national registry and
      repository for childhood IIM, which aims to improve knowledge, facilitate
      research and clinical trials, and ultimately to improve outcomes for these
      patients. METHODS: A UK-wide network of centres and research group was
      established to contribute to the study. Standardized patient assessment, data
      collection forms and sample protocols were agreed. The Biobank includes
      collection of peripheral blood mononuclear cells, serum, genomic DNA and biopsy
      material. An independent steering committee was established to oversee the use of
      data/samples. Centre training was provided for patient assessment, data
      collection and entry. RESULTS: Ten years after inception, the study has recruited
      285 children, of which 258 have JDM or juvenile PM; 86% of the cases have
      contributed the biological samples. Serial sampling linked directly to the
      clinical database makes this a highly valuable resource. The study has been a
      platform for 20 sub-studies and attracted considerable funding support.
      Assessment of children with myositis in contributing centres has changed through
      participation in this study. CONCLUSIONS: This establishment of a multicentre
      registry and Biobank has facilitated research and contributed to progress in the
      management of a complex group of rare muscloskeletal conditions.

PMID- 20823095
TI  - Usefulness of a centralized system of data collection for the development of an
      international multicentre registry of spondyloarthritis.
AB  - OBJECTIVE: To present the usefulness of a centralized system of data collection
      for the development of an international multicentre registry of SpA. METHOD: The
      originality of this registry consists in the creation of a virtual network of
      researchers in a computerized Internet database. From its conception, the
      registry was meant to be a dynamic acquiring system. RESULTS: REGISPONSER has two
      developing phases (Conception and Universalization) and gathers several evolving
      secondary projects (REGISPONSER-EARLY, REGISPONSER-AS, ESPERANZA and RESPONDIA).
      Each sub-project answered the necessity of having more specific and complete data
      of the patients even from the onset of the disease so, in the end, obtaining a
      well-defined picture of SpAs spectrum in the Spanish population. CONCLUSION:
      REGISPONSER is the first dynamic SpA database composed of cohorts with a
      significant number of patients distributed by specific diagnosis, which provides
      basic specific information of the sub-cohorts useful for patients' evaluation in
      rheumatology ambulatory consulting.

PMID- 20823096
TI  - Lysophosphatidic acid-activated Cl- current activity in human systemic sclerosis
      skin fibroblasts.
AB  - OBJECTIVES: SSc (scleroderma) is an often fatal disease characterized by
      widespread tissue fibrosis. Fibroblasts play a key role in SSc-associated
      fibrosis. This study was designed to determine: (i) whether fibroblasts isolated
      from skin of patients with SSc have increased lysophosphatidic acid-activated Cl-
      current (IClLPA) activity vs healthy controls; (ii) whether myofibroblast
      differentiation is involved in SSc skin fibrosis; and (iii) whether SSc
      fibroblasts have different proliferation rates vs controls. METHODS: Skin
      biopsies were taken from involved and uninvolved skin of SSc patients and
      controls. Whole-cell perforated patch-clamping was used to measure IClLPA
      activity in fibroblasts isolated and cultured from these biopsies. Western
      blotting was used to measure alpha-smooth muscle actin (alpha-SMA). Proliferation
      was measured using a colorimetric assay. RESULTS: Fibroblasts cultured from SSc
      skin show significantly increased IClLPA activity following LPA exposure compared
      with control skin fibroblasts. alpha-SMA protein was significantly increased in
      cultured SSc skin fibroblasts vs controls. No significant differences in
      proliferation rates were found. CONCLUSIONS: Elevated IClLPA activity is a
      hallmark of SSc skin fibroblasts. Blocking IClLPA activation may be a new
      therapeutic approach for treating SSc-associated fibrosis.

PMID- 20823097
TI  - Haemodynamic effects of rolofylline in the treatment of patients with heart
      failure and impaired renal function.
AB  - AIMS: The direct effects of adenosine A1 receptor antagonists on haemodynamic
      parameters in patients with acute heart failure (HF) remain largely unknown.
      METHODS AND RESULTS: We evaluated the haemodynamic effects of the AA(1)RA
      rolofylline in 59 HF patients with concomitant renal impairment (estimated
      creatinine clearance 20-80 mL/min). Placebo or rolofylline 30 mg was administered
      as a 4 h infusion followed by intravenous (i.v.) loop diuretic administration.
      Haemodynamic measurements were carried out hourly up to 8 h post-dosing by
      pulmonary artery catheterization. Urine output, fractional excretion of sodium,
      potassium, urea, and uric acid, and blood urea nitrogen (BUN) and creatinine
      levels were also measured. In both groups, the changes from baseline in all
      haemodynamic indices except mean pulmonary artery pressure (PAP) were not
      clinically significant. Mean [95% confidence interval (CI)] PAP showed a placebo
      adjusted decrease with rolofylline of -1.5 (-4.1, 1.1)mmHg at Hour 4 and -3.5
      mmHg (95% CI: -6.2, -0.2) at Hour 8. There was a significant increase with
      rolofylline in diuresis [placebo-corrected mean (95% CI) change of 68 (20,
      116)mL/h at Hour 2-4 and 103 (21, 185)mL/h at Hour 4-8] and in fractional
      excretion of sodium, potassium, and uric acid. Placebo-corrected changes in
      plasma levels of creatinine and BUN with rolofylline were non-significant.
      CONCLUSION: Single administration of rolofylline in patients with HF and impaired
      renal function produced a slight decrease in mean PAP and consistently increased
      diuresis and natriuresis without compromising renal function, both before and
      after administration of i.v. loop diuretics.

PMID- 20823098
TI  - Novel small molecule glucagon-like peptide-1 receptor agonist stimulates insulin
      secretion in rodents and from human islets.
AB  - OBJECTIVE: The clinical effectiveness of parenterally-administered glucagon-like
      peptide-1 (GLP-1) mimetics to improve glucose control in patients suffering from
      type 2 diabetes strongly supports discovery pursuits aimed at identifying and
      developing orally active, small molecule GLP-1 receptor agonists. The purpose of
      these studies was to identify and characterize novel nonpeptide agonists of the
      GLP-1 receptor. RESEARCH DESIGN AND METHODS: Screening using cells expressing the
      GLP-1 receptor and insulin secretion assays with rodent and human islets were
      used to identify novel molecules. The intravenous glucose tolerance test (IVGTT)
      and hyperglycemic clamp characterized the insulinotropic effects of compounds in
      vivo. RESULTS: Novel low molecular weight pyrimidine-based compounds that
      activate the GLP-1 receptor and stimulate glucose-dependent insulin secretion are
      described. These molecules induce GLP-1 receptor-mediated cAMP signaling in
      HEK293 cells expressing the GLP-1 receptor and increase insulin secretion from
      rodent islets in a dose-dependent manner. The compounds activate GLP-1 receptor
      signaling, both alone or in an additive fashion when combined with the endogenous
      GLP-1 peptide; however, these agonists do not compete with radiolabeled GLP-1 in
      receptor-binding assays. In vivo studies using the IVGTT and the hyperglycemic
      clamp in Sprague Dawley rats demonstrate increased insulin secretion in compound
      treated animals. Further, perifusion assays with human islets isolated from a
      donor with type 2 diabetes show near-normalization of insulin secretion upon
      compound treatment. CONCLUSIONS: These studies characterize the insulinotropic
      effects of an early-stage, small molecule GLP-1 receptor agonist and provide
      compelling evidence to support pharmaceutical optimization.

PMID- 20823099
TI  - Antiatherosclerotic and renoprotective effects of ebselen in the diabetic
      apolipoprotein E/GPx1-double knockout mouse.
AB  - OBJECTIVE: To investigate the effect of the GPx1-mimetic ebselen on diabetes
      associated atherosclerosis and renal injury in a model of increased oxidative
      stress. RESEARCH DESIGN AND METHODS: The study was performed using diabetic
      apolipoprotein E/GPx1 (ApoE(-/-)GPx1(-/-))-double knockout (dKO) mice, a model
      combining hyperlipidemia and hyperglycemia with increased oxidative stress. Mice
      were randomized into two groups, one injected with streptozotocin, the other with
      vehicle, at 8 weeks of age. Groups were further randomized to receive either
      ebselen or no treatment for 20 weeks. RESULTS: Ebselen reduced diabetes
      associated atherosclerosis in most aortic regions, with the exception of the
      aortic sinus, and protected dKO mice from renal structural and functional injury.
      The protective effects of ebselen were associated with a reduction in oxidative
      stress (hydroperoxides in plasma, 8-isoprostane in urine, nitrotyrosine in the
      kidney, and 4-hydroxynonenal in the aorta) as well as a reduction in VEGF, CTGF,
      VCAM-1, MCP-1, and Nox2 after 10 weeks of diabetes in the dKO aorta. Ebselen also
      significantly reduced the expression of proteins implicated in fibrosis and
      inflammation in the kidney as well as reducing related key intracellular
      signaling pathways. CONCLUSIONS: Ebselen has an antiatherosclerotic and
      renoprotective effect in a model of accelerated diabetic complications in the
      setting of enhanced oxidative stress. Our data suggest that ebselen effectively
      repletes the lack of GPx1, and indicate that ebselen may be an effective
      therapeutic for the treatment of diabetes-related atherosclerosis and
      nephropathy. Furthermore, this study highlights the feasibility of addressing two
      diabetic complications with one treatment regimen through the unifying approach
      of targeted antioxidant therapy.

PMID- 20823100
TI  - Impact of physical inactivity on subcutaneous adipose tissue metabolism in
      healthy young male offspring of patients with type 2 diabetes.
AB  - OBJECTIVE: Physical inactivity is a risk factor for type 2 diabetes and may be
      more detrimental in first-degree relative (FDR) subjects, unmasking underlying
      defects of metabolism. Using a positive family history of type 2 diabetes as a
      marker of increased genetic risk, the aim of this study was to investigate the
      impact of physical inactivity on adipose tissue (AT) metabolism in FDR subjects.
      RESEARCH DESIGN AND METHODS: A total of 13 FDR and 20 control (CON) subjects
      participated in the study. All were studied before and after 10 days of bed rest
      using the glucose clamp technique combined with measurements of glucose uptake,
      lipolysis, and lactate release from subcutaneous abdominal (SCAAT) and femoral
      (SCFAT) adipose tissue by the microdialysis technique. Additionally, mRNA
      expression of lipases was determined in biopsies from SCAAT. RESULTS: Before bed
      rest, the FDR subjects revealed significantly increased glucose uptake in SCAAT.
      Furthermore, mRNA expression of lipases was significantly decreased in the SCAAT
      of FDR subjects. Bed rest significantly decreased lipolysis and tended to
      increase glucose uptake in the SCFAT of both CON and FDR subjects. In response to
      bed rest, SCAAT glucose uptake significantly increased in CON subjects but not in
      FDR subjects. CONCLUSIONS: FDR subjects exhibit an abnormal AT metabolism
      including increased glucose uptake prior to bed rest. However, the differences
      between FDR and CON subjects in AT metabolism were attenuated during bed rest due
      to relatively more adverse changes in CON subjects compared with FDR subjects.
      Physical inactivity per se is not more deleterious in FDR subjects as compared
      with CON subjects with respect to derangements in AT metabolism.

PMID- 20823101
TI  - High levels of serum prolactin protect against diabetic retinopathy by increasing
      ocular vasoinhibins.
AB  - OBJECTIVE: Increased retinal vasopermeability (RVP) occurs early in diabetes and
      is crucial for the development of sight-threatening proliferative diabetic
      retinopathy (DR). The hormone prolactin (PRL) is proteolytically processed to
      vasoinhibins, a family of peptides that inhibit the excessive RVP related to DR.
      Here, we investigate the circulating levels of PRL in association with DR in men
      and test whether increased circulating PRL, by serving as a source of ocular
      vasoinhibins, can reduce the pathological RVP in diabetes. RESEARCH DESIGN AND
      METHODS: Serum PRL was evaluated in 40 nondiabetic and 181 diabetic men at
      various stages of DR. Retinal vasoinhibins were measured in rats rendered
      hyperprolactinemic by placing two anterior pituitary grafts under the kidney
      capsule and in PRL receptor-null mice. RVP was determined in hyperprolactinemic
      rats subjected to the intraocular injection of vascular endothelial growth factor
      (VEGF) or made diabetic with streptozotocin. RESULTS: The circulating levels of
      PRL increased in diabetes and were higher in diabetic patients without
      retinopathy than in those with proliferative DR. In rodents, hyperprolactinemia
      led to vasoinhibin accumulation within the retina; genetic deletion of the PRL
      receptor prevented this effect, indicating receptor-mediated incorporation of
      systemic PRL into the eye. Hyperprolactinemia reduced both VEGF-induced and
      diabetes-induced increase of RVP. This reduction was blocked by bromocriptine, an
      inhibitor of pituitary PRL secretion, which lowers the levels of circulating PRL
      and retinal vasoinhibins. CONCLUSIONS: Circulating PRL influences the progression
      of DR after its intraocular conversion to vasoinhibins. Inducing
      hyperprolactinemia may represent a novel therapy against DR.

PMID- 20823102
TI  - Maternal antioxidant supplementation prevents adiposity in the offspring of
      Western diet-fed rats.
AB  - OBJECTIVE: Obesity in pregnancy significantly increases the risk of the offspring
      developing obesity after birth. The aims of this study were to test the
      hypothesis that maternal obesity increases oxidative stress during fetal
      development, and to determine whether administration of an antioxidant supplement
      to pregnant Western diet-fed rats would prevent the development of adiposity in
      the offspring. RESEARCH DESIGN AND METHODS: Female Sprague Dawley rats were
      started on the designated diet at 4 weeks of age. Four groups of animals were
      studied: control chow (control); control + antioxidants (control+Aox); Western
      diet (Western); and Western diet + antioxidants (Western+Aox). The rats were
      mated at 12 to 14 weeks of age, and all pups were weaned onto control diet.
      RESULTS: Offspring from dams fed the Western diet had significantly increased
      adiposity as early as 2 weeks of age as well as impaired glucose tolerance
      compared with offspring of dams fed a control diet. Inflammation and oxidative
      stress were increased in preimplantation embryos, fetuses, and newborns of
      Western diet-fed rats. Gene expression of proadipogenic and lipogenic genes was
      altered in fat tissue of rats at 2 weeks and 2 months of age. The addition of an
      antioxidant supplement decreased adiposity and normalized glucose tolerance.
      CONCLUSIONS; Inflammation and oxidative stress appear to play a key role in the
      development of increased adiposity in the offspring of Western diet-fed pregnant
      dams. Restoration of the antioxidant balance during pregnancy in the Western diet
      fed dam is associated with decreased adiposity in offspring.

PMID- 20823103
TI  - High glucose increases lysyl oxidase expression and activity in retinal
      endothelial cells: mechanism for compromised extracellular matrix barrier
      function.
AB  - OBJECTIVE: In diabetes, retinal vascular basement membrane (BM) undergoes
      significant thickening and compromises vessel function including increased
      vascular permeability, a prominent lesion of early diabetic retinopathy. In this
      study we determined whether altered expression and activity of lysyl oxidase
      (LOX), a cross-linking enzyme, may compromise vascular basement membrane
      functional integrity under high-glucose (HG) conditions. RESEARCH DESIGN AND
      METHODS: Rat retinal endothelial cells (RRECs) grown in normal (5 mmol/l) or HG
      (30 mmol/l glucose) medium for 7 days were assessed for expression of LOX and
      proLOX by Western blot analysis and LOX enzyme activity. To determine whether HG
      alters cellular distribution patterns of LOX and proLOX, immunostaining with
      respective antibodies was performed. Similarly, cells grown in normal or HG
      medium were subjected to both LOX inhibition with beta-aminopropionitrile (BAPN)
      and by small interfering RNA knockdown, and respectively examined for cell
      monolayer permeability. Additionally, retinas of streptozotocin (STZ)-induced
      diabetic rats were analyzed to determine if diabetes altered LOX expression.
      RESULTS: Western blot analysis revealed significantly increased LOX and proLOX
      expression in cells grown in HG medium compared with those grown in normal
      medium. The increased LOX level was strikingly similar to LOX upegulation in the
      diabetic retinas. In cells grown in HG medium, LOX activity and cell monolayer
      permeability was significantly increased, as were LOX and proLOX immunostaining.
      Small interfering RNA- or BAPN-induced-specific blockage of LOX expression or
      activity, respectively, reduced cell monolayer permeability. CONCLUSIONS: HG
      induced increased LOX expression and activity compromises barrier functional
      integrity, a prominent lesion of diabetic retinopathy.

PMID- 20823104
TI  - A soluble guanylate cyclase-dependent mechanism is involved in the regulation of
      net hepatic glucose uptake by nitric oxide in vivo.
AB  - OBJECTIVE: We previously showed that elevating hepatic nitric oxide (NO) levels
      reduced net hepatic glucose uptake (NHGU) in the presence of portal glucose
      delivery, hyperglycemia, and hyperinsulinemia. The aim of the present study was
      to determine the role of a downstream signal, soluble guanylate cyclase (sGC), in
      the regulation of NHGU by NO. RESEARCH DESIGN AND METHODS: Studies were performed
      on 42-h-fasted conscious dogs fitted with vascular catheters. At 0 min,
      somatostatin was given peripherally along with 4* basal insulin and basal
      glucagon intraportally. Glucose was delivered at a variable rate via a leg vein
      to double the blood glucose level and hepatic glucose load throughout the study.
      From 90 to 270 min, an intraportal infusion of the sGC inhibitor 1H-[1,2,4]
      oxadiazolo[4,3-a] quinoxalin-1-one (ODQ) was given in -sGC (n = 10) and -sGC/+NO
      (n = 6), whereas saline was given in saline infusion (SAL) (n = 10). The -sGC/+NO
      group also received intraportal SIN-1 (NO donor) to elevate hepatic NO from 180
      to 270 min. RESULTS: In the presence of 4* basal insulin, basal glucagon, and
      hyperglycemia (2* basal ), inhibition of sGC in the liver enhanced NHGU
      (mg/kg/min; 210-270 min) by ~55% (2.9 +/- 0.2 in SAL vs. 4.6 +/- 0.5 in -sGC).
      Further elevating hepatic NO failed to reduce NHGU (4.5 +/- 0.7 in -sGC/+NO). Net
      hepatic carbon retention (i.e., glycogen synthesis; mg glucose
      equivalents/kg/min) increased to 3.8 +/- 0.2 in -sGC and 3.8 +/- 0.4 in -sGC/+NO
      vs. 2.4 +/- 0.2 in SAL (P < 0.05). CONCLUSIONS: NO regulates liver glucose uptake
      through a sGC-dependent pathway. The latter could be a target for pharmacologic
      intervention to increase meal-associated hepatic glucose uptake in individuals
      with type 2 diabetes.

PMID- 20823105
TI  - Impact of different empirical antibiotic treatment regimens for community
      acquired pneumonia on the emergence of Clostridium difficile.
AB  - BACKGROUND: Treatment of community-acquired pneumonia (CAP) with newer
      fluoroquinolones may contribute to selection for Clostridium difficile. We
      studied the prevalence of C. difficile carriage and C. difficile infection (CDI)
      on admission, and nosocomial acquisition rates in patients hospitalized for CAP
      and compared different empirical treatment strategies. METHODS: In a prospective
      study among patients admitted for antibiotic treatment of CAP, consecutive stool
      and skin samples were collected and cultured for C. difficile. Cultured isolates
      were typed by PCR ribotyping and characterized for toxinogenicity. RESULTS: In
      total, 20 of 107 (18.7%) patients included carried C. difficile. Various
      ribotypes were found and 14 (70%) isolates were toxinogenic. On admission,
      prevalence of C. difficile carriage was 9.4% (n=9), of which 22% also carried C.
      difficile on the skin and one patient had mild CDI with persistent positive
      cultures. The overall nosocomial acquisition rate of C. difficile carriage was
      11.2%. No nosocomially acquired CDI occurred. Acquisition rates of C. difficile
      were 11.9% (5/45) in moxifloxacin-, 11.1% (5/47) in beta-lactam- and 9.0% (1/14)
      in beta-lactam plus macrolide- or fluoroquinolone-treated patients (P=0.84). Risk
      factors for C. difficile carriage were intravenous antibiotic treatment >7 days
      [odds ratio (OR) 3.89; 95% confidence interval (CI) 1.30 to 11.79] and
      hospitalization during the past 3 months (OR 4.08; 95% CI 1.40 to 11.90).
      CONCLUSIONS: In a non-outbreak setting with a low endemic rate, the prevalence of
      C. difficile carriage in patients admitted because of CAP is high and nosocomial
      acquisition rates for C. difficile colonization are 11%. Fluoroquinolones were
      not associated with increased acquisition rates for C. difficile as compared with
      other empirical regimens for CAP.

PMID- 20823106
TI  - Disparities in hepatocellular carcinoma survival among Californians of Asian
      ancestry, 1988 to 2007.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) represents a significant health
      disparity affecting Asian Americans, a population comprised of distinct ethnic
      groups. The purpose of this article is to analyze Californians of Asian ancestry
      with HCC with respect to socioeconomic status, demographic factors, stage of
      disease, treatment received, and survival. METHODS: To investigate ethnic
      differences in survival, we analyzed ethnically disaggregated data from 6,068
      Californians of Asian ancestry with HCC diagnosed in 1988 to 2007 and reported to
      the California Cancer Registry. RESULTS: Compared with the average of all ethnic
      groups, cause-specific mortality was significantly higher among Laotian/Hmong
      [hazard ratio, 2.08; 95% confidence interval (95% CI), 1.78-2.44] and Cambodian
      patients (hazard ratio, 1.26; 95% CI, 1.06-1.51), groups with higher proportions
      of their populations at low levels of socioeconomic status; in addition,
      Laotian/Hmong patients disproportionately presented at later stages of disease,
      with only 3% receiving local surgical treatment, resection, or liver
      transplantation. After adjustment for time of diagnosis, age at diagnosis,
      gender, geographic region, stage at diagnosis, type of surgery, and socioeconomic
      status, survival disparities remained for both groups (Laotian/Hmong hazard
      ratio, 1.51; 95% CI, 1.28-1.79; Cambodian hazard ratio, 1.24; 95% CI, 1.03-1.48).
      CONCLUSIONS: Our hypothesis that survival outcomes would differ by ethnicity was
      verified. IMPACT: Research is needed not only to develop more effective
      treatments for HCC but also to develop community-based interventions to recruit
      Asian Americans, particularly Laotian/Hmong and Cambodians, for hepatitis B
      screening and into medical management to prevent or detect this tumor at an early
      stage.

PMID- 20823107
TI  - The FOXM1 transcriptional factor promotes the proliferation of leukemia cells
      through modulation of cell cycle progression in acute myeloid leukemia.
AB  - FOXM1 is an important cell cycle regulator and regulates cell proliferation. In
      addition, FOXM1 has been reported to contribute to oncogenesis in various
      cancers. However, it is not clearly understood how FOXM1 contributes to acute
      myeloid leukemia (AML) cell proliferation. In this study, we investigated the
      cellular and molecular function of FOXM1 in AML cells. The FOXM1 messenger RNA
      (mRNA) expressed in AML cell lines was predominantly the FOXM1B isoform, and its
      levels were significantly higher than in normal high aldehyde dehydrogenase
      activity (ALDH(hi)) cells. Reduction of FOXM1 expression in AML cells inhibited
      cell proliferation compared with control cells, through induction of G(2)/M cell
      cycle arrest, a decrease in the protein expression of Aurora kinase B, Survivin,
      Cyclin B1, S-phase kinase-associated protein 2 and Cdc25B and an increase in the
      protein expression of p21(Cip1) and p27(Kip1). FOXM1 messenger RNA (mRNA) was
      overexpressed in all 127 AML clinical specimens tested (n = 21, 56, 32 and 18 for
      M1, M2, M4 and M5 subtypes, respectively). Compared with normal ALDH(hi) cells,
      FOXM1 gene expression was 1.65- to 2.26-fold higher in AML cells. Moreover, the
      FOXM1 protein was more strongly expressed in AML-derived ALDH(hi) cells compared
      with normal ALDH(hi) cells. In addition, depletion of FOXM1 reduced colony
      formation of AML-derived ALDH(hi) cells due to inhibition of Cdc25B and Cyclin B1
      expression. In summary, we found that FOXM1B mRNA is predominantly expressed in
      AML cells and that aberrant expression of FOXM1 induces AML cell proliferation
      through modulation of cell cycle progression. Thus, inhibition of FOXM1
      expression represents an attractive target for AML therapy.

PMID- 20823108
TI  - Honokiol, a phytochemical from the Magnolia plant, inhibits photocarcinogenesis
      by targeting UVB-induced inflammatory mediators and cell cycle regulators:
      development of topical formulation.
AB  - To develop newer and more effective chemopreventive agents for skin cancer, we
      assessed the effect of honokiol, a phytochemical from the Magnolia plant, on
      ultraviolet (UV) radiation-induced skin tumorigenesis using the SKH-1 hairless
      mouse model. Topical treatment of mice with honokiol in a hydrophilic cream-based
      topical formulation before or after UVB (180 mJ/cm(2)) irradiation resulted in a
      significant protection against photocarcinogenesis in terms of tumor multiplicity
      (28-60%, P < 0.05 to <0.001) and tumor volume per tumor-bearing mouse (33-80%, P
      < 0.05 to 0.001, n = 20). Honokiol also inhibited and delayed the malignant
      progression of papillomas to carcinomas. To investigate the in vivo molecular
      targets of honokiol efficacy, tumors and tumor-uninvolved skin samples from the
      tumor-bearing mice were analyzed for inflammatory mediators, cell cycle
      regulators and survival signals using immunostaining, western blotting and enzyme
      linked immunosorbent assay. Treatment with honokiol significantly inhibited UVB
      induced expression of cyclooxygenase-2, prostaglandin E(2) (P < 0.001),
      proliferating cell nuclear antigen and proinflammatory cytokines, such as tumor
      necrosis factor-alpha (P < 0.001), interleukin (IL)-1beta (P < 0.01) and IL-6 (P
      < 0.001) in the skin as well as in skin tumors. Western blot analysis revealed
      that honokiol: (i) inhibited the levels of cyclins D1, D2 and E and associated
      cyclin-dependent kinases (CDKs)2, CDK4 and CDK6, (ii) upregulated Cip/p21 and
      Kip/p27 and (iii) inhibited the levels of phosphatidylinositol 3-kinase and the
      phosphorylation of Akt at Ser(473) in UVB-induced skin tumors. Together, our
      results indicate that honokiol holds promise for the prevention of UVB-induced
      skin cancer by targeting inflammatory mediators, cell cycle regulators and cell
      survival signals in UVB-exposed skin.

PMID- 20823109
TI  - Imaging of coronary atherosclerosis: intravascular ultrasound.
AB  - Atherosclerosis is the main cause of coronary heart disease, which is today the
      leading cause of death worldwide and will continue to be the first in the world
      in 2030. In the formation of atherosclerotic coronary lesions, a critical primary
      step is the accumulation and oxidation of low-density lipoprotein (LDL)
      particles. Oxidized-LDL favours leucocyte recruitment and their activation, as
      well as cell death. This leads to generation of complex atherosclerotic plaques.
      These plaques have a high content of necrotic core, a thin inflamed fibrous cap
      (intense accumulation of macrophages) and scarce presence of smooth muscle cells
      (i.e. thin-capped fibroatheroma). At early stages of the formation of the
      atheroma, the remodelling of the vessel wall usually prevents plaque from
      encroaching on the lumen, thereby masking the presence of atheroma on
      angiography. In contrast, greyscale intravascular ultrasound can fully assess the
      extension of the disease axially and longitudinally. This intravascular imaging
      technique has played a vital role in advancing our understanding of the
      pathophysiology of coronary artery disease, and in the development of novel
      cardiovascular drugs and device therapies. This intravascular imaging technology
      and its clinical and research applications are discussed in more detail below.

PMID- 20823110
TI  - Genetic counselling and testing in cardiomyopathies: a position statement of the
      European Society of Cardiology Working Group on Myocardial and Pericardial
      Diseases.
AB  - Advances in molecular genetics present new opportunities and challenges for
      cardiologists who manage patients and families with cardiomyopathies. The aims of
      this position statement of the European Society of Cardiology Working Group on
      Myocardial and Pericardial Diseases are to review the general issues related to
      genetic counselling, family screening and genetic testing in families with a
      cardiomyopathy, and to provide key messages and suggestions for clinicians
      involved in their management.

PMID- 20823111
TI  - Protamine contents and P1/P2 ratio in human spermatozoa from smokers and non
      smokers.
AB  - BACKGROUND: Protamine content is necessary for proper sperm chromatin
      condensation and subsequent male fertility. The exact effect of smoking on male
      fertility remains controversial. The objective of this study was to evaluate the
      effect of smoking on protamine content of sperm in smoker and non-smoker
      patients. METHODS: Protamines 1 (P1) and 2 (P2) were quantified by gel
      electrophoresis in the sperm of 53 smokers and 63 non-smokers. Sperm DNA
      fragmentation was analyzed employing the terminal deoxynucleotidyltransferase
      mediated dUTP nick-end labelling (TUNEL) assay and non-condensed chromatin was
      evaluated using chromomycin A(3) (CMA(3)). Levels of smoking and oxidative stress
      markers were determined in seminal plasma using an enzyme linked immunosorbant
      assay (ELISA) and chemical reactions. RESULTS: Protamine 2 concentrations were
      significantly lower (P < 0.050) in smokers than in non-smokers. In contrast P1/P2
      ratios were significantly higher (P < 0.010) in smokers (1.34 +/- 0.46 ng/10(6)
      sperm) than in non-smokers (1.11 +/- 0.20 ng/10(6) sperm). The oxidative stress
      and smoking markers, reactive oxygen species (ROS), malondialdehyde, 8
      Hydroxyguanosine (8-OHdG) and cotinine were significantly higher (P < 0.010) in
      smokers than in non-smokers, and correlated significantly (P < 0.050) with P1/P2
      ratios. P2 showed significant negative (P < 0.050) correlations with ROS, 8-OHdG
      and cotinine. CMA(3) and TUNEL were also significantly higher (P < 0.010) in
      smokers (36.4 +/- 8.1 and 17.4 +/- 5.3%) than in non-smokers (29.8 +/- 7.1 and
      11.3 +/- 4.2%). CONCLUSIONS: This is the first study to evaluate the effect of
      smoking on protamines. Abnormal elevation of the P1/P2 ratio appears to be
      associated with aberrant P2 expression in smokers. These results suggest that
      induced oxidative stress by cigarette smoking may have significant inverse effect
      on the protamination process by disrupting P2.

PMID- 20823112
TI  - Cigarette smoking during early pregnancy reduces the number of embryonic germ and
      somatic cells.
AB  - BACKGROUND: Cigarette smoking during pregnancy is associated with negative
      reproductive consequences for male fetuses in adult life such as reduced
      testicular volume and sperm concentration. The present study evaluates the number
      of germ and somatic cells present in human embryonic first-trimester gonads in
      relation to maternal smoking. METHODS: The study includes 24 human first
      trimester testes, aged 37-68 days post-conception, obtained from women undergoing
      legal termination of pregnancy. A questionnaire was used to obtain information
      about smoking and drinking habits during pregnancy. Validated stereological
      methods were used to estimate gonadal cell numbers in histological sections.
      Results were also evaluated in the context of previously published data on
      ovaries from our laboratory. RESULTS: A significant reduction in the number of
      germ cells by 55% [95% confidence interval (CI) 74-21% reduction, P = 0.004] and
      somatic cells by 37% (95% CI 59-3%, P = 0.023) was observed in testes prenatally
      exposed to maternal cigarette smoking, compared with unexposed. The effect of
      maternal smoking was dose-dependent being higher in the heavy smokers and
      remained consistent after adjusting for possible confounders such as alcohol and
      coffee consumption (P = 0.002). The number of germ cells in embryonic gonads,
      irrespective of gender, was also significantly reduced by 41% (95% CI 58-19%, P =
      0.001) in exposed versus non-exposed embryonic gonads. CONCLUSIONS: Prenatal
      exposure to maternal cigarette smoke reduces the number of germ and somatic cells
      in embryonic male and female gonads. This effect may have long-term consequences
      on the future fertility of exposed offspring. These findings may provide one
      potential cause of the reduced fertility observed during recent years.

PMID- 20823113
TI  - Oxygen consumption and ROS production are increased at the time of fertilization
      and cell cleavage in bovine zygotes.
AB  - BACKGROUND: Oxygen consumption is a key indicator of metabolic activity within
      embryos. Increased oxidative activity and REDOX changes at the time of
      fertilization have been suggested to signal Ca(2+) oscillations after sperm
      penetration. The objective of the present study was to determine the oxygen
      consumption and the REDOX status of zygotes and early embryos at the time of
      sperm penetration and cell cleavage and to investigate how metabolism relates to
      key temporal events and developmental competence. METHODS: Individual oxygen
      consumption rates of bovine in vitro matured oocytes and presumptive zygotes (n =
      101) were measured using the Nanorespirometer at 0, 7, 12, 17 and 24 h after IVF.
      Using the Embryoscope, oxygen-consumption profiles of individual oocytes and
      embryos (n = 75) were recorded repeatedly from 6 h until 30 h after IVF and time
      lapse images were acquired, at intervals of ~36 min. Oocytes and embryos were
      stained with Hoechst 33342 and visualization of nuclear stage was performed by
      fluorescence microscopy. To determine the REDOX status, cohorts of oocytes and
      zygotes (n = 55) were individually stained with REDOX-Sensor Red CC-1 and Hoechst
      33342 at 0, 7, 12, 17 and 24 h after IVF and subsequently imaged by confocal
      microscopy. RESULTS: A peak of oxygen consumption was observed at the time of
      fertilization and a smaller rise and fall in oxygen consumption could be detected
      prior to the first cell cleavage. Increased reactive oxygen species production
      was also observed at 7 h and then at 24 h after IVF, just preceding the first
      embryonic cleavage. CONCLUSIONS: There are specific events during embryo
      development that appear to be associated with a change in oxygen consumption and
      REDOX state, indicating that both have a role in sperm-mediated oocyte activation
      and cell cleavage in bovine embryos.

PMID- 20823114
TI  - The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human
      endometrial stromal cells.
AB  - BACKGROUND: Decidualization, the differentiation of endometrial stromal cells is
      a crucial step for successful implantation of an embryo, development of the
      placenta and completion of pregnancy to term. Epigenetic mechanisms are thought
      to be strongly involved in the regulation of processes controlling implantation,
      placentation, organ formation and foetal growth. Recent studies suggest that
      decreased DNA methylation facilitates a receptive endometrium. Hence, the aim of
      this project was to compare the transcriptional profile changes induced by the
      inhibitor of DNA methylation, 5-Aza-2'-deoxycytidine (AZA) to the transcriptional
      changes that happen during decidualization. METHODS AND RESULTS: When DNA
      methylation was inhibited in a human endometrial stromal cell (HESC) line with
      AZA, it resulted in the fibroblast-like stromal cells being transformed into
      decidual-like morphology after 9 days. Expression of both prolactin and insulin
      like growth factor binding protein-1, the two established decidualization marker
      genes, were minimally up-regulated by AZA after 10 days of treatment. In a
      microarray of a three-way experiment between AZA-treated and
      oestradiol/progestin/cAMP-treated [medroxy-progesterone acetate (MPA)-mix] HESC
      and the untreated controls, we detected more than 1000 common genes that had a
      significant difference of expression compared with the controls. AZA-treated
      cells in the microarray significantly expressed 76 genes in common with the MPA
      mix treated cells, and AZA treatment also differentially regulated 148 genes
      independently to that of MPA-mix treatment. The MPA-mix regulated at least 36
      genes in the cell adhesion, extracellular matrix remodelling and RhoGTPase
      cytoskeletal reorganization pathway; AZA regulated 19 of these genes in common
      and 15 other RhoGTPase pathway genes. CONCLUSION: AZA induced some
      decidualization-like responses of endometrial stromal cells independently of
      progestins or cAMP, possibly via the cytoskeletal reorganization pathway of the
      RhoGTPase family.

PMID- 20823115
TI  - Pregnancy-triggered antiphospholipid syndrome in a patient with multiple late
      miscarriages.
AB  - Antiphospholipid syndrome (APS) is a multisystemic disorder of coagulation
      causing thrombosis in the arterial and venous system as well as pregnancy-related
      complications such as miscarriage, stillbirth, preterm delivery and pre
      eclampsia. The disease is characterized by the autoimmune production of
      antibodies against phospholipid, a substance found in the cell membrane. We here
      report the case of a patient with four second trimester miscarriages, who apart
      from a heterozygous plasminogen activator-inhibitor-1 mutation, had no risk
      factors explaining her condition. In the subsequent pregnancy she was therefore
      put on low-molecular-weight heparin, aspirin and granulocyte colony-stimulating
      factor. Antiphospholipid antibodies (APL), which had been negative before
      gestation, increased and remained high throughout pregnancy, thus suggesting a
      pregnancy-induced or -aggravated APS. The patient was kept on the above-mentioned
      medication and delivered a healthy male baby by Caesarean section after an
      otherwise uneventful pregnancy. Thus, in order to diagnose and treat pregnancy
      triggered APS in patients with unexplained recurrent miscarriage, screening for
      APL should also be performed at several time points after conception.

PMID- 20823116
TI  - H-Y antibody titers are increased in unexplained secondary recurrent miscarriage
      patients and associated with low male : female ratio in subsequent live births.
AB  - BACKGROUND: The birth of a boy is significantly more common than a girl prior to
      secondary recurrent miscarriage (SRM) and is associated with a poorer chance of a
      subsequent live birth. Children born after SRM are more likely to be girls. High
      titer antisera specific for male antigens (H-Y) have been shown to arrest
      development of male bovine embryos efficiently. We consequently questioned the
      role of H-Y antibodies in women with SRM. METHODS: Serum samples from patients
      with unexplained SRM (n = 84), unexplained primary recurrent miscarriage (PRM) (n
      = 12) and healthy women (n = 37) were obtained. The samples were taken during
      pregnancy (gestational weeks 4-5) for 77 (80%) of the patients. Enzyme-linked
      immunosorbent assay was used to detect immunoglobulin G antibodies that
      specifically recognized any of the five recombinant H-Y proteins (EIF1AY, RPS4Y1,
      ZFY, DDX3Y and UTY) and their H-X homologs. RESULTS: H-Y-specific antibodies were
      more frequent in SRM patients (46%) compared with female controls (19%, P =
      0.004) and PRM patients (8%, P = 0.01). The presence of H-Y antibodies in early
      pregnancy was associated with a low male: female birth ratio among the subsequent
      live births, as only 12% of children born to H-Y antibody-positive patients were
      boys compared with 44% boys born to H-Y antibody negative patients (P = 0.03).
      CONCLUSIONS: The high frequency of H-Y antibody-positive SRM patients and the
      association between the presence of these antibodies in early pregnancy and the
      low number of male offspring, suggest that maternal immune responses against H-Y
      antigens can cause pregnancy losses. Further exploring these mechanisms may
      increase our understanding of unexplained SRM.

PMID- 20823117
TI  - Appearance of an oocyte activation-related substance during spermatogenesis in
      mice and humans.
AB  - BACKGROUND: Recently we reported that an oocyte activation ability in human and
      mouse sperm is associated with head flatness or the presence of perinuclear theca
      (PT) substance, MN13, which is an oocyte activation-related protein localized on
      the post-acrosomal sheath (PAS). As such, we hypothesize that the appearance of
      oocyte activation ability is stage-specifically regulated and depends on the
      formation of the acrosome or PAS/PT in spermatids. METHODS: We monitored the
      appearance and movement of MN13 as a PT-specific molecule during spermatogenesis
      and analysed how the MN13 localization is affected in mouse and human
      globozoospermic acrosomeless sperm. RESULTS: MN13 was first detected on the
      surface of acrosomic vesicles, i.e. on the nascent outer acrosomal membrane of
      step 5-6 round spermatids (Sb1 spermatids in human), and it was then translocated
      via the outer acrosomal membrane surface to the most distal region of the
      acrosome in step 7 round spermatids (Sb2 spermatids). As spermatids elongated,
      MN13 was translocated via the cytoplasmic space between the nuclear envelope and
      the overlying plasma membrane towards the post-acrosomal region, and it was
      organized on the top of the nascent PAS that was typically found in step 14
      elongated spermatids (Sd1 spermatids). In contrast, MN13 was not found in any
      GOPC-deficient spermatids, which completely lack the acrosome but have manchettes
      (microtubule bundles), nor in mouse and human acrosomeless sperm. CONCLUSIONS:
      The MN13 appearance or the MN13-related PAS/PT formation is highly dependant on
      acrosome formation; the MN13-related oocyte activation factor/ability is stage
      specifically acquired in elongating/elongated spermatids.

PMID- 20823118
TI  - Four KH domains of the C. elegans Bicaudal-C ortholog GLD-3 form a globular
      structural platform.
AB  - Caenorhabditis elegans GLD-3 is a five K homology (KH) domain-containing protein
      involved in the translational control of germline-specific mRNAs during
      embryogenesis. GLD-3 interacts with the cytoplasmic poly(A)-polymerase GLD-2. The
      two proteins cooperate to recognize target mRNAs and convert them into a
      polyadenylated, translationally active state. We report the 2.8-A-resolution
      crystal structure of a proteolytically stable fragment encompassing the KH2, KH3,
      KH4, and KH5 domains of C. elegans GLD-3. The structure reveals that the four
      tandem KH domains are organized into a globular structural unit. The domains are
      involved in extensive side-by-side interactions, similar to those observed in
      previous structures of dimeric KH domains, as well as head-to-toe interactions.
      Small-angle X-ray scattering reconstructions show that the N-terminal KH domain
      (KH1) forms a thumb-like protrusion on the KH2-KH5 unit. Although KH domains are
      putative RNA-binding modules, the KH region of GLD-3 is unable in isolation to
      cross-link RNA. Instead, the KH1 domain mediates the direct interaction with the
      poly(A)-polymerase GLD-2, pointing to a function of the KH region as a protein
      protein interaction platform.

PMID- 20823119
TI  - Clustered O-glycans of IgA1: defining macro- and microheterogeneity by use of
      electron capture/transfer dissociation.
AB  - IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the
      world. Aberrantly glycosylated IgA1, with galactose (Gal)-deficient hinge region
      (HR) O-glycans, plays a pivotal role in the pathogenesis of the disease. It is
      not known whether the glycosylation defect occurs randomly or preferentially at
      specific sites. We have described the utility of activated ion-electron capture
      dissociation (AI-ECD) mass spectrometric analysis of IgA1 O-glycosylation.
      However, locating and characterizing the entire range of O-glycan attachment
      sites are analytically challenging due to the clustered serine and threonine
      residues in the HR of IgA1 heavy chain. To address this problem, we analyzed all
      glycoforms of the HR glycopeptides of a Gal-deficient IgA1 myeloma protein,
      mimicking the aberrant IgA1 in patients with IgAN, by use of a combination of IgA
      specific proteases + trypsin and AI-ECD Fourier transform ion cyclotron resonance
      (FT-ICR) tandem mass spectrometry (MS/MS). The IgA-specific proteases provided a
      variety of IgA1 HR fragments that allowed unambiguous localization of all O
      glycosylation sites in the six most abundant glycoforms, including the sites
      deficient in Gal. Additionally, this protocol was adapted for on-line liquid
      chromatography (LC)-AI-ECD MS/MS and LC-electron transfer dissociation MS/MS
      analysis. Our results thus represent a new clinically relevant approach that
      requires ECD/electron transfer dissociation-type fragmentation to define the
      molecular events leading to pathogenesis of a chronic kidney disease.
      Furthermore, this work offers generally applicable principles for the analysis of
      clustered sites of O-glycosylation.

PMID- 20823120
TI  - Trimming of ubiquitin chains by proteasome-associated deubiquitinating enzymes.
AB  - The proteasome generally recognizes substrate via its multiubiquitin chain
      followed by ATP-dependent unfolding and translocation of the substrate from the
      regulatory particle into the proteolytic core particle to be degraded. Substrate
      bound ubiquitin groups are for the most part not delivered to the core particle
      and broken down together with substrate but instead recovered as intact free
      ubiquitin and ubiquitin chains. Substrate deubiquitination on the proteasome is
      mediated by three distinct deubiquitinating enzymes associated with the
      regulatory particle: RPN11, UCH37, and USP14. RPN11 cleaves at the base of the
      ubiquitin chain where it is linked to the substrate, whereas UCH37 and apparently
      USP14 mediate a stepwise removal of ubiquitin from the substrate by disassembling
      the chain from its distal tip. In contrast to UCH37 and USP14, RPN11 shows
      degradation-coupled activity; RPN11-mediated deubiquitination is apparently
      delayed until the proteasome is committed to degrade the substrate. Accordingly,
      RPN11-mediated deubiquitination promotes substrate degradation. In contrast,
      removal of ubiquitin prior to commitment could antagonize substrate degradation
      by promoting substrate dissociation from the proteasome. Emerging evidence
      suggests that USP14 and UCH37 can both suppress substrate degradation in this
      way. One line of study has shown that small molecule USP14 inhibitors can enhance
      proteasome function in cells, which is consistent with this model. Enhancing
      protein degradation could potentially have therapeutic applications for diseases
      involving toxic proteins that are proteasome substrates. However, the
      responsiveness of substrates to inhibition of proteasomal deubiquitinating
      enzymes may vary substantially. This substrate specificity and its mechanistic
      basis should be addressed in future studies.

PMID- 20823122
TI  - Increased power for the analysis of label-free LC-MS/MS proteomics data by
      combining spectral counts and peptide peak attributes.
AB  - Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics
      provides a wealth of information about proteins present in biological samples. In
      bottom-up LC-MS/MS-based proteomics, proteins are enzymatically digested into
      peptides prior to query by LC-MS/MS. Thus, the information directly available
      from the LC-MS/MS data is at the peptide level. If a protein-level analysis is
      desired, the peptide-level information must be rolled up into protein-level
      information. We propose a principal component analysis-based statistical method,
      ProPCA, for efficiently estimating relative protein abundance from bottom-up
      label-free LC-MS/MS data that incorporates both spectral count information and LC
      MS peptide ion peak attributes, such as peak area, volume, or height. ProPCA may
      be used effectively with a variety of quantification platforms and is easily
      implemented. We show that ProPCA outperformed existing quantitative methods for
      peptide-protein roll-up, including spectral counting methods and other methods
      for combining LC-MS peptide peak attributes. The performance of ProPCA was
      validated using a data set derived from the LC-MS/MS analysis of a mixture of
      protein standards (the UPS2 proteomic dynamic range standard introduced by The
      Association of Biomolecular Resource Facilities Proteomics Standards Research
      Group in 2006). Finally, we applied ProPCA to a comparative LC-MS/MS analysis of
      digested total cell lysates prepared for LC-MS/MS analysis by alternative lysis
      methods and show that ProPCA identified more differentially abundant proteins
      than competing methods.

PMID- 20823123
TI  - Predictors of long-term survival in nonagenarians: the NonaSantfeliu study.
AB  - BACKGROUND: few studies have prospectively evaluated long-term predictors of
      mortality in nonagenarians. OBJECTIVE: to determine predictors of death in a
      nonagenarian cohort after 5 years of follow-up. DESIGN: a prospective community
      based study. SETTING: a community-based study. SUBJECTS: one hundred and eighty
      six nonagenarians both living in the community and institutionalised. METHODS:
      functional status was determined by the Lawton-Brody and Barthel Indexes (BI) and
      cognition by the Spanish version of the mental state examination (MEC). The
      Charlson Index was used to measure comorbidity. Nutritional status was evaluated
      by the short version of the Mini-Nutritional Assessment questionnaire. RESULTS:
      mortality after 5 years was 75.53%. Patients who did not survive were
      significantly older, with lower cognitive and functional performance, with
      diminished visual acuity, higher comorbidity, high risk of malnutrition, higher
      number of drugs taken and a higher percentage of patients with the diagnosis of
      dyslipidaemia, heart failure or previous stroke. Cox regression analysis,
      identified the Charlson Index (hazard ratio 1.23, 95% CI 1.09-1.37) and MEC
      (hazard ratio 0.98, 95% CI 0.97-0.99) as independent predictors of mortality
      after 5 years. CONCLUSIONS: better cognitive status and lesser comorbidity at
      baseline are the best predictors to identify which nonagenarians survived after a
      5-year follow-up period.

PMID- 20823121
TI  - The Penicillium chrysogenum extracellular proteome. Conversion from a food
      rotting strain to a versatile cell factory for white biotechnology.
AB  - The filamentous fungus Penicillium chrysogenum is well-known by its ability to
      synthesize beta-lactam antibiotics as well as other secondary metabolites. Like
      other filamentous fungi, this microorganism is an excellent host for secretion of
      extracellular proteins because of the high capacity of its protein secretion
      machinery. In this work, we have characterized the extracellular proteome
      reference map of P. chrysogenum Wisconsin 54-1255 by two-dimensional gel
      electrophoresis. This method allowed the correct identification of 279 spots by
      peptide mass fingerprinting and tandem MS. These 279 spots included 328 correctly
      identified proteins, which corresponded to 131 different proteins and their
      isoforms. One hundred and two proteins out of 131 were predicted to contain
      either classical or nonclassical secretion signal peptide sequences, providing
      evidence of the authentic extracellular location of these proteins. Proteins with
      higher representation in the extracellular proteome were those involved in plant
      cell wall degradation (polygalacturonase, pectate lyase, and glucan 1,3-beta
      glucosidase), utilization of nutrients (extracellular acid phosphatases and 6
      hydroxy-d-nicotine oxidase), and stress response (catalase R). This filamentous
      fungus also secretes enzymes specially relevant for food industry, such as
      sulfydryl oxidase, dihydroxy-acid dehydratase, or glucoamylase. The
      identification of several antigens in the extracellular proteome also highlights
      the importance of this microorganism as one of the main indoor allergens.
      Comparison of the extracellular proteome among three strains of P. chrysogenum,
      the wild-type NRRL 1951, the Wis 54-1255 (an improved, moderate penicillin
      producer), and the AS-P-78 (a penicillin high-producer), provided important
      insights to consider improved strains of this filamentous fungus as versatile
      cell-factories of interest, beyond antibiotic production, for other aspects of
      white biotechnology.

PMID- 20823124
TI  - A multicentre randomised controlled trial of day hospital-based falls prevention
      programme for a screened population of community-dwelling older people at high
      risk of falls.
AB  - OBJECTIVE: to determine the clinical effectiveness of a day hospital-delivered
      multifactorial falls prevention programme, for community-dwelling older people at
      high risk of future falls identified through a screening process. DESIGN:
      multicentre randomised controlled trial. SETTING: eight general practices and
      three day hospitals based in the East Midlands, UK. PARTICIPANTS: three hundred
      and sixty-four participants, mean age 79 years, with a median of three falls risk
      factors per person at baseline. INTERVENTIONS: a day hospital-delivered
      multifactorial falls prevention programme, consisting of strength and balance
      training, a medical review and a home hazards assessment. MAIN OUTCOME MEASURE:
      rate of falls over 12 months of follow-up, recorded using self-completed monthly
      diaries. RESULTS: one hundred and seventy-two participants in each arm
      contributed to the primary outcome analysis. The overall falls rate during follow
      up was 1.7 falls per person-year in the intervention arm compared with 2.0 falls
      per person-year in the control arm. The stratum-adjusted incidence rate ratio was
      0.86 (95% CI 0.73-1.01), P = 0.08, and 0.73 (95% CI 0.51-1.03), P = 0.07 when
      adjusted for baseline characteristics. There were no significant differences
      between the intervention and control arms in any secondary outcomes. CONCLUSION:
      this trial did not conclusively demonstrate the benefit of a day hospital
      delivered multifactorial falls prevention programme, in a population of older
      people identified as being at high risk of a future fall.

PMID- 20823125
TI  - Frequency of inappropriate drugs in primary care: analysis of a sample of
      immobile patients who received periodic home visits.
AB  - BACKGROUND: drug intake is associated with the risk of drug-related problems
      (DRPs), e.g. the intake of PIM. OBJECTIVE: the proportion of potentially
      inappropriate medication (PIM) taken by elderly people was analysed. DESIGN:
      community-based, prospective cohort study. SETTING: ambulatory health-care sector
      in a German rural area. SUBJECTS: seven hundred and forty-four patients with age
      >65 years and regular intake of drugs. METHODS: comprehensive home medication
      review (HMR) provided by specially qualified assistants of GP practices using
      electronic case reporting forms (eCRFs), and GP's diagnoses were extracted from
      patients' health records. Updated Beers' list of Fick et al. was used to detect
      PIM for patients >65 years and drug-condition interaction. RESULTS: a total of
      18% (n= 134) of the patients received 163 inappropriate drugs. Out of these
      drugs, most prevalent PIM were benzodiazepine derivates (n= 45). Out of all
      drugs, 25 drug-condition interactions were identified. The intake of PIM was
      slightly associated with self-reported falls (: 0.1074; P= 0.0244). Multivariate
      logistic regression showed significant results for the number of taken substances
      (OR = 1.176; 95% CI 1.121-1.234, P< 0.001). CONCLUSIONS: a high proportion of
      patients taking PIM in a community-based setting were investigated. Statistical
      associations with self-reported falls were found. Confounding may influence data.
      Further research to investigate findings is needed.

PMID- 20823126
TI  - Renal function in a narrow-age cohort of adults at 79 and 87 years.

PMID- 20823127
TI  - Walking and night-time restlessness in mild-to-moderate dementia: a randomized
      controlled trial.

PMID- 20823128
TI  - Atypical familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D
      and STXBP2 overlaps with primary immunodeficiency diseases.
AB  - BACKGROUND: Familial hemophagocytic lymphohistiocytosis is a genetic disorder of
      lymphocyte cytotoxicity that usually presents in the first two years of life and
      has a poor prognosis unless treated by hematopoietic stem cell transplantation.
      Atypical courses with later onset and prolonged survival have been described, but
      no detailed analysis of immunological parameters associated with typical versus
      atypical forms of familial hemophagocytic lymphohistiocytosis has been performed.
      DESIGN AND METHODS: We analyzed disease manifestations, NK-cell and T-cell
      cytotoxicity and degranulation, markers of T-cell activation and B-cell
      differentiation as well as Natural Killer T cells in 8 patients with atypical
      familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D and
      STXBP2. RESULTS: All but one patient with atypical familial hemophagocytic
      lymphohistiocytosis carried at least one splice-site mutation in UNC13D or
      STXBP2. In most patients episodes of hemophagocytic lymphohistiocytosis were
      preceded or followed by clinical features typically associated with
      immunodeficiency, such as chronic active Epstein Barr virus infection, increased
      susceptibility to bacterial infections, granulomatous lung or liver disease,
      encephalitis or lymphoma. Five of 8 patients had hypogammaglobulinemia and
      reduced memory B cells. Most patients had a predominance of activated CD8(+) T
      cells and low numbers of Natural Killer T cells. When compared to patients with
      typical familial hemophagocytic lymphohistiocytosis, NK-cell cytotoxicity and NK
      cell and CTL degranulation were impaired to a similar extent. However, in
      patients with an atypical course NK-cell degranulation could be partially
      reconstituted by interleukin-2 and cytotoxic T-cell cytotoxicity in vitro was
      normal. CONCLUSIONS: Clinical and immunological features of atypical familial
      hemophagocytic lymphohistiocytosis show an important overlap to primary
      immunodeficiency diseases (particularly common variable immunodeficiency and X
      linked lymphoproliferative syndrome) and must, therefore, be considered in a
      variety of clinical presentations. We show that degranulation assays are helpful
      screening tests for the identification of such patients.

PMID- 20823129
TI  - Analysis of 12,517 inhabitants of a Sardinian geographic isolate reveals that
      predispositions to thrombocytopenia and thrombocytosis are inherited traits.
AB  - BACKGROUND: Thrombocytopenia is a common finding in several diseases but almost
      nothing is known about the prevalence of thrombocytopenia in the general
      population. We examined the prevalence of thrombocytopenia and determinants of
      platelet count in a healthy population with a wide age range. DESIGN AND METHODS:
      We performed a cross-sectional study on 12,517 inhabitants of ten villages (80%
      of residents) in a secluded area of Sardinia (Ogliastra). Participants underwent
      a complete blood count evaluation and a structured questionnaire, used to collect
      epidemiological data. RESULTS: We observed a platelet count lower than 150 *
      109/L in 3.2% (2.8%-3.6%) of females and 4.8% (4.3%-5.4%) of males, with a value
      of 3.9% (3.6%-4.3%) in the entire population. Thrombocytopenia was mild (platelet
      count: 100 * 109/L-150 * 109/L), asymptomatic and not associated with other
      cytopenias or overt disorders in most cases. Its standardized prevalence was
      quite different in different villages, with values ranging from 1.5% to 6.8%, and
      was negatively correlated with the prevalence of a mild form of thrombocytosis,
      which ranged from 0.9% to 4.5%. Analysis of platelet counts across classes of age
      revealed that platelet number decreased progressively with aging. As a
      consequence, thrombocytopenia was nearly absent in young people and its
      prevalence increased regularly during lifetime. The opposite occurred for
      thrombocytosis. CONCLUSIONS: Given the high genetic differentiation among
      Ogliastra villages with "high" and "low" platelet counts and the substantial
      heritability of this quantitative trait (54%), we concluded that the propensity
      to present mild and transient thrombocytosis in youth and to acquire mild
      thrombocytopenia during aging are new genetic traits.

PMID- 20823130
TI  - Histone deacetylase 2 is required for chromatin condensation and subsequent
      enucleation of cultured mouse fetal erythroblasts.
AB  - BACKGROUND: During the final stages of differentiation of mammalian erythroid
      cells, the chromatin is condensed and enucleated. We previously reported that Rac
      GTPases and their downstream target, mammalian homolog of Drosophila diaphanous 2
      (mDia2), are required for enucleation of in vitro cultured mouse fetal liver
      erythroblasts. However, it is not clear how chromatin condensation is achieved
      and whether it is required for enucleation. DESIGN AND METHODS: Mouse fetal liver
      erythroblasts were purified from embryonic day 14.5 pregnant mice and cultured in
      erythropoietin-containing medium. Enucleation was determined by flow-cytometry
      based analysis after treatment with histone deacetylase inhibitors or infection
      with lentiviral short hairpin RNA. RESULTS: We showed that histone deacetylases
      play critical roles in chromatin condensation and enucleation in cultured mouse
      fetal liver erythroblasts. Enzymatic inhibition of histone deacetylases by
      trichostatin A or valproic acid prior to the start of enucleation blocked
      chromatin condensation, contractile actin ring formation and enucleation. We
      further demonstrated that histone deacetylases 1, 2, 3 and 5 are highly expressed
      in mouse fetal erythroblasts. Short hairpin RNA down-regulation of histone
      deacetylase 2, but not of the other histone deacetylases, phenotypically mimicked
      the effect of trichostatin A or valproic acid treatment, causing significant
      inhibition of chromatin condensation and enucleation. Importantly, knock-down of
      histone deacetylase 2 did not affect erythroblast proliferation, differentiation,
      or apoptosis. CONCLUSIONS: These results identify histone deacetylase 2 as an
      important regulator, mediating chromatin condensation and enucleation in the
      final stages of mammalian erythropoiesis.

PMID- 20823131
TI  - p-ERK1/2 is a predictive factor of response to erythropoiesis-stimulating agents
      in low/int-1 myelodysplastic syndromes.
AB  - Serum erythropoietin level less than 100U/L and a transfusion requirement of less
      than 2 units per month are the best predictive factors for response to treatment
      by erythropoiesis-stimulating agents in low/int-1 myelodysplastic syndromes. To
      investigate the factors influencing the response to erythropoiesis-stimulating
      agents, we enrolled 127 low/int-1 myelodysplastic syndrome patients at diagnosis
      in a biological study of erythropoiesis. The 54 non-responders had a
      significantly lower number of burst-forming unit-erythroid and colony-forming
      unit-erythroid than responders. Erythropoietin-dependent proliferation and
      survival, and phospho (p)-ERK1/2 expression in steady state and after
      erythropoietin stimulation were defective in cultured erythroblasts. By flow
      cytometry, p-ERK1/2 was significantly lower in bone marrow CD45(-)/CD71(+)/GPA(
      )cells from non-responders compared to responders or controls. Receiver Operator
      Characteristic curve analysis showed that this flow cytometry test was a
      sensitive biomarker for predicting the response to erythropoiesis-stimulating
      agents.

PMID- 20823132
TI  - The pre-B-cell receptor associated protein VpreB3 is a useful diagnostic marker
      for identifying c-MYC translocated lymphomas.
AB  - BACKGROUND: During B-cell development, precursor B cells transiently express the
      pre-B-cell receptor composed of MU heavy chain complexed with VpreB and lambda5
      surrogate light chain polypeptides. Recent profiling studies unexpectedly
      revealed abundant transcripts of one member of the VpreB family, VpreB3, in a
      subset of mature B cells and Burkitt lymphoma. DESIGN AND METHODS: Here we used a
      novel antibody to investigate the normal expression pattern of VpreB3 protein in
      human hematopoietic and lymphoid tissues, and to determine whether VpreB3 could
      serve as a useful diagnostic biomarker for select B-cell lymphomas. RESULTS: We
      found that VpreB3 protein is normally expressed by precursor B cells in bone
      marrow and by a subset of normal germinal center B cells in secondary lymphoid
      organs. Among lymphoid malignancies, we found an association between VpreB3
      expression and B-cell tumors with c-MYC abnormalities. VpreB3 was highly
      expressed in all cases of Burkitt lymphoma, whether of endemic or sporadic origin
      (44/44 cases, 100%), all cases of B-cell lymphoma, unclassifiable, with features
      intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (5/5
      cases, 100%), and the majority of diffuse large B-cell lymphomas harboring a c
      MYC translocation (15/18 cases, 83%). The expression of VpreB3 in diffuse large B
      cell lymphomas without a c-MYC translocation was associated with c-MYC polysomy
      in 25/75 cases (33%) but only rarely observed in diffuse large B-cell lymphomas
      lacking a c-MYC abnormality (9/98 cases, 9%). CONCLUSIONS: We conclude that for B
      cell tumors with features suggesting a possible c-MYC translocation, such as
      intermediate to large cell size and high proliferation rate, the presence of
      VpreB3 should prompt subsequent confirmatory genetic testing, whereas the absence
      of VpreB3 is virtually always associated with wild-type c-MYC alleles.

PMID- 20823133
TI  - Delta-tocotrienol protects mouse and human hematopoietic progenitors from gamma
      irradiation through extracellular signal-regulated kinase/mammalian target of
      rapamycin signaling.
AB  - BACKGROUND: Exposure to gamma-radiation causes rapid hematopoietic cell apoptosis
      and bone marrow suppression. However, there are no approved radiation
      countermeasures for the acute radiation syndrome. In this study, we demonstrated
      that natural delta-tocotrienol, one of the isomers of vitamin E, significantly
      enhanced survival in total body lethally irradiated mice. We explored the effects
      and mechanisms of delta-tocotrienol on hematopoietic progenitor cell survival
      after gamma-irradiation in both in vivo and in vitro experiments. DESIGN AND
      METHODS: CD2F1 mice and human hematopoietic progenitor CD34(+) cells were treated
      with delta-tocotrienol or vehicle control 24 h before or 6 h after gamma
      irradiation. Effects of delta-tocotrienol on hematopoietic progenitor cell
      survival and regeneration were evaluated by clonogenicity studies, flow
      cytometry, and bone marrow histochemical staining. delta-tocotrienol and gamma
      irradiation-induced signal regulatory activities were assessed by
      immunofluorescence staining, immunoblotting and short-interfering RNA assay.
      RESULTS: delta-tocotrienol displayed significant radioprotective effects. A
      single injection of delta-tocotrienol protected 100% of CD2F1 mice from total
      body irradiation-induced death as measured by 30-day post-irradiation survival.
      delta-tocotrienol increased cell survival, and regeneration of hematopoietic
      microfoci and lineage(-)/Sca-1(+)/ckit(+) stem and progenitor cells in irradiated
      mouse bone marrow, and protected human CD34(+) cells from radiation-induced
      damage. delta-tocotrienol activated extracellular signal-related kinase 1/2
      phosphorylation and significantly inhibited formation of DNA-damage marker gamma
      H2AX foci. In addition, delta-tocotrienol up-regulated mammalian target of
      rapamycin and phosphorylation of its downstream effector 4EBP-1. These
      alterations were associated with activation of mRNA translation regulator eIF4E
      and ribosomal protein S6, which is responsible for cell survival and growth.
      Inhibition of extracellular signal-related kinase 1/2 expression by short
      interfering RNA abrogated delta-tocotrienol-induced mammalian target of rapamycin
      phosphorylation and clonogenicity, and increased gamma-H2AX foci formation in
      irradiated CD34(+) cells. CONCLUSIONS: Our data indicate that delta-tocotrienol
      protects mouse bone marrow and human CD34(+) cells from radiation-induced damage
      through extracellular signal-related kinase activation-associated mammalian
      target of rapamycin survival pathways.

PMID- 20823134
TI  - Detection of genomic aberrations in molecularly defined Burkitt's lymphoma by
      array-based, high resolution, single nucleotide polymorphism analysis.
AB  - BACKGROUND: Knowledge about the genetic lesions that occur in Burkitt's lymphoma,
      besides the pathognomonic IG-MYC translocations, is limited. DESIGN AND METHODS:
      Thirty-nine molecularly-defined Burkitt's lymphomas were analyzed with high
      resolution single-nucleotide polymorphism chips for genomic imbalances and
      uniparental disomy. Imbalances were correlated to expression profiles and
      selected micro-RNA analysis. Translocations affecting the MYC locus were studied
      by fluorescence in situ hybridization. RESULTS: We detected 528 copy number
      changes, defining 29 recurrently imbalanced regions. Five hundred and eighteen
      regions of uniparental disomy were found, but these were rarely recurrent.
      Combined imbalance mapping and expression profiling revealed a strong correlation
      between copy number and expression. Several recurrent imbalances affected the MYC
      pathway: the micro-RNA-supercluster 17-92 was frequently gained and the
      transcription factor E2F2 was recurrently deleted. Molecular Burkitt's lymphoma
      lacking MYC translocations showed MYC gains. Amplifications of the polymerase
      iota gene were associated with increased frequency of positions scored as
      aberrant. CONCLUSIONS: The present findings suggest that uniparental disomies do
      not play a major role in the pathogenesis of Burkitt's lymphoma, whereas some
      genes may contribute to the development of this lymphoma through gene dosage
      effects. Amplifications of the polymerase iota gene may be functionally linked
      with increased genomic alterations in Burkitt's lymphoma. The pattern and rarity
      of chromosomal changes detectable, even at the high resolution employed here,
      together with aberrations of genes regulating MYC activity, support the
      hypothesis that deregulation of the MYC pathway is the major force driving the
      pathogenesis of Burkitt's lymphoma, but show that this deregulation is more
      complex than previously known.

PMID- 20823135
TI  - Nuclear factor-kappaB inducing kinase is required for graft-versus-host disease.
AB  - BACKGROUND: Donor T lymphocytes are directly responsible for graft-versus-host
      disease. Molecules important in T-cell function may, therefore, be appropriate
      targets for graft-versus-host disease therapy and/or prophylaxis. Here we
      analyzed whether nuclear factor-kappa B inducing kinase might have a role in
      graft-versus-host disease. DESIGN AND METHODS: We studied the expression of
      nuclear factor-kappa B inducing kinase in human samples from patients with graft
      versus-host disease. We also explored the effect of nuclear factor-kappa B
      inducing kinase in a murine model of graft-versus-host disease using donor cells
      from aly/aly mice (deficient in nuclear factor-kappa B inducing kinase) and
      C57BL/6 mice (control). RESULTS: We detected expression of nuclear factor-kappa B
      inducing kinase in T-lymphocytes in the pathological lesions of patients with
      acute graft-versus-host disease. Mice transplanted with aly/aly T lymphocytes did
      not develop graft-versus-host disease at all, while mice receiving C57BL/6 cells
      died of a lethal form of the disease. Deficiency of nuclear factor-kappa B
      inducing kinase did not affect the engrafting ability of donor T cells, but
      severely impaired their expansion capacity early after transplantation, and
      aly/aly T cells showed a higher proportion of apoptosis than did C57BL/6 T cells.
      Effector T lymphocytes were the T-cell subset most affected by nuclear factor
      kappa B inducing kinase deficiency. We also detected lower amounts of
      inflammatory cytokines in the serum of mice receiving aly/aly T cells than in the
      serum of mice receiving C57BL/6 T cells. CONCLUSIONS: Our results show that
      nuclear factor-kappa B inducing kinase has a role in graft-versus-host disease by
      maintaining the viability of activated alloreactive T lymphocytes.

PMID- 20823136
TI  - Molecular mechanisms associated with leukemic transformation of MPL-mutant
      myeloproliferative neoplasms.
AB  - Somatic activating mutations in MPL, the thrombopoietin receptor, occur in the
      myeloproliferative neoplasms, although virtually nothing is known about their
      role in evolution to acute myeloid leukemia. In this study, the MPL T487A
      mutation, identified in de novo acute myeloid leukemia, was not detected in 172
      patients with a myeloproliferative neoplasm. In patients with a prior MPL W515L
      mutant myeloproliferative neoplasm, leukemic transformation was accompanied by
      MPL-mutant leukemic blasts, was seen in the absence of prior cytoreductive
      therapy and often involved loss of wild-type MPL by mitotic recombination.
      Moreover, clonal analysis of progenitor colonies at the time of leukemic
      transformation revealed the presence of multiple genetically distinct but
      phylogenetically-related clones bearing different TP53 mutations, implying a
      mutator-phenotype and indicating that leukemic transformation may be preceded by
      the parallel expansion of diverse hematopoietic clones.

PMID- 20823137
TI  - Dynamic chromosomal rearrangements in Hodgkin's lymphoma are due to ongoing three
      dimensional nuclear remodeling and breakage-bridge-fusion cycles.
AB  - BACKGROUND: Hodgkin's lymphoma is characterized by the presence of mono-nucleated
      Hodgkin cells and bi- to multi-nucleated Reed-Sternberg cells. We have recently
      shown telomere dysfunction and aberrant synchronous/asynchronous cell divisions
      during the transition of Hodgkin cells to Reed-Sternberg cells.1 DESIGN AND
      METHODS: To determine whether overall changes in nuclear architecture affect
      genomic instability during the transition of Hodgkin cells to Reed-Sternberg
      cells, we investigated the nuclear organization of chromosomes in these cells.
      RESULTS: Three-dimensional fluorescent in situ hybridization revealed irregular
      nuclear positioning of individual chromosomes in Hodgkin cells and, more so, in
      Reed-Sternberg cells. We characterized an increasingly unequal distribution of
      chromosomes as mono-nucleated cells became multi-nucleated cells, some of which
      also contained chromosome-poor 'ghost' cell nuclei. Measurements of nuclear
      chromosome positions suggested chromosome overlaps in both types of cells.
      Spectral karyotyping then revealed both aneuploidy and complex chromosomal
      rearrangements: multiple breakage-bridge-fusion cycles were at the origin of the
      multiple rearranged chromosomes. This conclusion was challenged by super
      resolution three-dimensional structured illumination imaging of Hodgkin and Reed
      Sternberg nuclei. Three-dimensional super resolution microscopy data documented
      inter-nuclear DNA bridges in multi-nucleated cells but not in mono-nucleated
      cells. These bridges consisted of chromatids and chromosomes shared by two Reed
      Sternberg nuclei. The complexity of chromosomal rearrangements increased as
      Hodgkin cells developed into multi-nucleated cells, thus indicating tumor
      progression and evolution in Hodgkin's lymphoma, with Reed-Sternberg cells
      representing the highest complexity in chromosomal rearrangements in this
      disease. CONCLUSIONS: This is the first study to demonstrate nuclear remodeling
      and associated genomic instability leading to the generation of Reed-Sternberg
      cells of Hodgkin's lymphoma. We defined nuclear remodeling as a key feature of
      Hodgkin's lymphoma, highlighting the relevance of nuclear architecture in cancer.

PMID- 20823138
TI  - Primary Ewing's sarcoma presenting as a Pancoast tumour.

PMID- 20823139
TI  - DNA repair: a reinvigorated therapeutic target.

PMID- 20823140
TI  - Regulation of excision repair cross-complementation group 1 by Snail contributes
      to cisplatin resistance in head and neck cancer.
AB  - PURPOSE: We investigated the mechanism and clinical significance of the
      epithelial-mesenchymal transition (EMT)-induced chemoresistance in head and neck
      squamous cell carcinoma (HNSCC). EXPERIMENTAL DESIGN: The correlation between the
      expression of different EMT regulators and chemoresistance genes, such as
      excision repair cross complementation group 1 (ERCC1), was evaluated in cancer
      cell lines from the NCI-60 database and four human HNSCC cell lines. Ectopic
      expression of Snail or short-interference RNA-mediated repression of Snail or
      ERCC1 was done in HNSCC cell lines. Cell viability was examined for cells after
      cisplatin treatment. A luciferase reporter assay and chromatin
      immunoprecipitation were used to identify the transcriptional regulation of ERCC1
      by Snail. Immunohistochemical analysis of Snail, Twist1, ERCC1, hypoxia inducible
      factor-1 alpha (HIF-1alpha), and NBS1 were done in samples from 72 HNSCC patients
      receiving cisplatin-based chemotherapy. RESULTS: The correlation between the
      expression of Snail and ERCC1 was confirmed in different cell lines, including
      HNSCC cells. In HNSCC cell lines, overexpression of Snail in the low endogenous
      Snail/ERCC1 cell lines FaDu or CAL-27 increased ERCC1 expression, and hypoxia or
      overexpression of NBS1 also upregulated ERCC1. Knockdown of Snail in the high
      endogenous Snail/ERCC1 cell line OECM-1 downregulated ERCC1 expression and
      attenuated cisplatin resistance. Furthermore, suppression of ERCC1 in Snail- or
      NBS1-overexpressing HNSCC cells enhanced sensitivity to cisplatin. Snail directly
      regulated ERCC1 transcription. In patients with HNSCC, coexpression of Snail and
      ERCC1 correlated with cisplatin resistance and a poor prognosis. CONCLUSIONS:
      Activation of ERCC1 by Snail is critical in the generation of cisplatin
      resistance of HNSCC cells.

PMID- 20823141
TI  - Jumonji domain containing 1A is a novel prognostic marker for colorectal cancer:
      in vivo identification from hypoxic tumor cells.
AB  - PURPOSE: This study aimed to identify novel hypoxia-inducible and prognostic
      markers in vivo from hypoxic tumor cells. EXPERIMENTAL DESIGN: Using carbonic
      anhydrase 9 and CD34 as a guide for hypoxic tumor cells, laser capture
      microdissection was used to isolate colorectal cancer (CRC) liver metastases. The
      samples were analyzed by microarray analysis, in parallel with five CRC cell
      lines cultured under hypoxic conditions. To evaluate the prognostic impact of the
      expression of certain genes, samples from a total of 356 CRC patients were
      analyzed by microarray or quantitative reverse transcription-PCR. In vitro
      mechanistic studies and in vivo therapeutic experiments were also done about a
      histone H3 Lys(9) demethylase, Jumonji domain containing 1A (JMJD1A). RESULTS:
      Several candidate genes were identified by microarray analysis of liver
      metastases and culturing of CRC cells under hypoxic conditions. Among them, we
      found that JMJD1A was a novel independent prognostic factor for CRC (P = 0.013).
      In vitro assays revealed that loss of JMJD1A by small interfering RNA treatment
      was associated with a reduction of proliferative activity and decrease in
      invasion of CRC cell lines. Furthermore, treatment with an adenovirus system for
      antisense JMJD1A construct displayed prominent therapeutic effects when injected
      into established tumor xenografts of the CRC cell lines HCT116 and DLD1.
      CONCLUSIONS: JMJD1A is a useful biomarker for hypoxic tumor cells and a
      prognostic marker that could be a promising therapeutic target against CRC.

PMID- 20823142
TI  - Poly (ADP-ribose) polymerase as a novel therapeutic target in cancer.
AB  - Cancer chemotherapy exploits limitations in repairing DNA damage in order to kill
      proliferating malignant cells. Recent evidence suggests that cancers within and
      across tissue types have specific defects in DNA repair pathways, and that these
      defects may predispose for sensitivity and resistance to various classes of
      cytotoxic agents. Poly (ADP-ribose) polymerase (PARP) and BRCA proteins are
      central to the repair of DNA strand breaks and, when defective, lead to the
      accumulation of mutations introduced by error-prone DNA repair. Breast, ovarian,
      and other cancers develop in the setting of BRCA deficiency, and these cancers
      may be more sensitive to cytotoxic agents that induce DNA strand breaks, as well
      as inhibitors of PARP activity. A series of recent clinical trials has tested
      whether PARP inhibitors can achieve synthetic lethality in BRCA-pathway-deficient
      tumors. Future studies must seek to identify sporadic cancers that harbor genomic
      instability, rendering susceptibility to agents that induce additional and lethal
      DNA damage.

PMID- 20823144
TI  - DNA damage and repair in translational oncology: an overview.
AB  - Unknown to early investigators, DNA damage and repair has been a major focus of
      anticancer therapy from the beginning of clinical oncology. From the early days
      of using x-irradiation, to the development of nitrogen mustard analogs, to
      today's more sophisticated approaches, DNA damage and repair has strongly
      impacted our ability to successfully treat human malignancy. This area of basic,
      translational, and clinical science is very broad. The traditional focus of DNA
      damage and repair has been on diseases such as Xeroderma pigmentosum, and
      attempting to understand the basic molecular mechanisms of DNA repair processes.
      It is only recently that we have begun to appreciate how we might modulate these
      processes to improve our ability to advance cancer care. No fewer than 10
      separate DNA repair processes are operative in higher organisms, and the total
      number of separable processes could be substantially higher. Some of our most
      useful clinical agents depend on causing DNA damage that is repaired by
      nucleotide excision repair. X-irradiation induces damage that is mostly repaired
      by base excision repair and double-strand break repair. We are now learning how
      to modulate select DNA repair pathways to benefit patients with breast cancer and
      other malignancies.

PMID- 20823143
TI  - Inhibitory effect of silibinin against azoxymethane-induced colon tumorigenesis
      in A/J mice.
AB  - PURPOSE: Colorectal cancer is the second leading cause of cancer-associated
      deaths, which suggests that more effort is needed to prevent/control this
      disease. Herein, for the first time, we investigate in vivo the efficacy of
      silibinin against azoxymethane-induced colon tumorigenesis in A/J mice.
      EXPERIMENTAL DESIGN: Five-week-old male mice were gavaged with vehicle or
      silibinin (250 and 750 mg/kg) for 25 weeks starting 2 weeks before initiation
      with azoxymethane (pretreatment regime) or for 16 weeks starting 2 weeks after
      the last azoxymethane injection (posttreatment regime). The mice were then
      sacrificed, and colon tissues were examined for tumor multiplicity and size, and
      molecular markers for proliferation, apoptosis, inflammation, and angiogenesis.
      RESULTS: Silibinin feeding showed a dose-dependent decrease in azoxymethane
      induced colon tumorigenesis with stronger efficacy in pretreatment versus
      posttreatment regimen. Mechanistic studies in tissue samples showed that
      silibinin inhibits cell proliferation as evident by a decrease (P < 0.001) in
      proliferating cell nuclear antigen and cyclin D1, and increased Cip1/p21 levels.
      Silibinin also decreased (P < 0.001) the levels of inducible nitric oxide
      synthase, cyclooxygenase-2, and vascular endothelial growth factor, suggesting
      its anti-inflammatory and antiangiogenic potential in this model. Further,
      silibinin increased cleaved caspase-3 and poly(ADP-ribose) polymerase levels,
      indicating its apoptotic effect. In other studies, colonic mucosa and tumors
      expressed high levels of beta-catenin, insulin-like growth factor-1 receptorbeta,
      phospho Glycogen synthase kinase-3beta, and phospho protein kinase B/pAkt
      proteins in azoxymethane-treated mice, which were strongly lowered (P < 0.001) by
      silibinin treatment. Moreover, azoxymethane reduced insulin-like growth factor
      binding protein-3 protein level, which was enhanced by silibinin. CONCLUSIONS:
      Silibinin targets beta-catenin and IGF-1Rbeta pathways for its chemopreventive
      efficacy against azoxymethane-induced colon carcinogenesis in A/J mice. Overall,
      these results support the translational potential of silibinin in colorectal
      cancer chemoprevention.

PMID- 20823145
TI  - "Contextual" synthetic lethality and/or loss of heterozygosity: tumor hypoxia and
      modification of DNA repair.
AB  - Hypoxia exists in every solid tumor and is associated with poor prognosis because
      of both local and systemic therapeutic resistance. Recent studies have focused on
      the interaction between tumor cell genetics and the dynamic state of oxygenation
      and metabolism. Hypoxia generates aggressive tumor cell phenotypes in part owing
      to ongoing genetic instability and a "mutator" phenotype. The latter may be due
      to suppression of DNA mismatch repair (MMR), nucleotide excision repair (NER),
      and double-strand break (DSB) repair. We propose a theoretical model in which
      hypoxia-mediated defects in DNA repair can lead to "contextual loss of
      heterozygosity" and drive oncogenesis. Additionally, hypoxia-mediated repair
      defects can be specifically targeted by DNA damaging agents and/or "contextual
      synthetic lethality" to kill repair-deficient cells and preserve the therapeutic
      ratio. These proposed concepts support the interrogation of solid tumors to
      document repair defects in both oxic and hypoxic tumor subregions as a conduit to
      novel clinical trials within the context of personalized medicine.

PMID- 20823146
TI  - Histone gammaH2AX and poly(ADP-ribose) as clinical pharmacodynamic biomarkers.
AB  - Tumor cells are often deficient in DNA damage response (DDR) pathways, and
      anticancer therapies are commonly based on genotoxic treatments using radiation
      and/or drugs that damage DNA directly or interfere with DNA metabolism, leading
      to the formation of DNA double-strand breaks (DSB), and ultimately to cell death.
      Because DSBs induce the phosphorylation of histone H2AX (gammaH2AX) in the
      chromatin flanking the break site, an antibody directed against gammaH2AX can be
      employed to measure DNA damage levels before and after patient treatment.
      Poly(ADP-ribose) polymerases (PARP1 and PARP2) are also activated by DNA damage,
      and PARP inhibitors show promising activity in cancers with defective homologous
      recombination (HR) pathways for DSB repair. Ongoing clinical trials are testing
      combinations of PARP inhibitors with DNA damaging agents. Poly(ADP-ribosylation),
      abbreviated as PAR, can be measured in clinical samples and used to determine the
      efficiency of PARP inhibitors. This review summarizes the roles of gammaH2AX and
      PAR in the DDR, and their use as biomarkers to monitor drug response and guide
      clinical trials, especially phase 0 clinical trials. We also discuss the choices
      of relevant samples for gammaH2AX and PAR analyses.

PMID- 20823148
TI  - Perspective on the pipeline of drugs being developed with modulation of DNA
      damage as a target.
AB  - Inhibitors of various elements of the DNA repair pathways have entered clinical
      development or are in late preclinical stages of drug development. It was
      initially considered that agents targeting DNA repair would act to overcome tumor
      resistance to chemotherapy and radiotherapy. More recent data have shown that
      targeting DNA repair pathways can be effective in selected tumors via a
      synthetically lethal route, with single agent activity having been shown with
      poly-ADP ribose polymerase (PARP) inhibitors. An increased understanding of the
      biology and interaction of the DNA repair pathways also means that rational
      combination of DNA repair inhibitors may also give great benefit in the clinic.

PMID- 20823147
TI  - Epigenetic modifications in double-strand break DNA damage signaling and repair.
AB  - Factors involved in the cellular response to double-strand break (DSB) DNA damage
      have been identified as potential therapeutic targets that would greatly
      sensitize cancer cells to radiotherapy and genotoxic chemotherapy. These targets
      could disable the repair machinery and/or reinstate normal cell-cycle checkpoint
      leading to growth arrest, senescence, and apoptosis. It is now clear that a major
      aspect of the DNA damage response occurs through specific interactions with
      chromatin structure and its modulation. It implicates highly dynamic
      posttranslational modifications of histones that are critical for DNA damage
      recognition and/or signaling, repair of the lesion, and release of cell-cycle
      arrest. Therefore, drugs that target the enzymes responsible for these
      modifications, or the protein modules reading them, have very high therapeutic
      potential. This review presents the current state of knowledge on the different
      chromatin modifications and their roles in each step of eukaryotic DSB DNA damage
      response.

PMID- 20823149
TI  - Therapeutic targeting of the DNA mismatch repair pathway.
AB  - The mismatch repair (MMR) pathway is involved in the removal of DNA base
      mismatches that arise either during DNA replication or are caused by DNA damage.
      Mutations in four genes involved in MMR, MSH2, MLH1, PMS2 and MSH6, predispose to
      a range of tumorigenic conditions, including hereditary nonpolyposis colon
      cancer, also known as Lynch syndrome. Here we discuss the canonical MMR pathway
      and the burgeoning evidence for noncanonical roles for the MMR genes, and
      highlight the therapeutic implications of MMR. In particular, we discuss how the
      DNA repair defect in MMR-deficient cancers could be exploited by the development
      of novel therapeutic strategies based on synthetic lethal approaches.

PMID- 20823150
TI  - Antibody-dependent natural killer cell-mediated cytotoxicity engendered by a
      kinase-inactive human HER2 adenovirus-based vaccination mediates resistance to
      breast tumors.
AB  - Cancer vaccines may have applications in the therapy and prevention of mammary
      carcinoma. To investigate such applications, we constructed a recombinant
      adenoviral vaccine expressing a kinase-inactive mutant form of human HER2 and
      introduced this into BALB/c wild-type (WT) or HER2 transgenic mice. Here, we
      report contributions by antibody responses and natural killer (NK) cells in tumor
      protection in this model. One i.p. vaccination protected WT mice from the HER2
      expressing mouse carcinoma D2F2/E2. Half of the HER2 transgenic mice were
      protected fully and long term after preventive vaccination. Tumor growth in mice
      that eventually developed neoplastic lesions was delayed. Protection in WT and
      HER2 transgenic mice was associated with high or low levels of IgG2a antibodies,
      respectively, whereas CTLs were observed in WT but not in HER2 transgenic mice.
      Depleting CD4(+) or CD8(+) cells in vaccinated WT mice had limited effects,
      suggesting that protection was largely independent of CD4(+) or CD8(+) T cells.
      In contrast, antibody-mediated tumor rejection seemed to contribute significantly
      based on a loss of protection in mice deficient for Fc-gamma RI/III or B cells.
      Further, a role for antibody-dependent cellular cytotoxicity (ADCC) mediated by
      NK cells was indicated by evidence that vaccine protection could be abolished by
      in vivo depletion of NK cells. Lastly, NK cells and immune sera purified from WT
      or HER2 transgenic mice exhibited efficient ADCC of HER2-expressing tumor cells
      in vitro. Our findings define a critical requirement for NK cells in vaccine
      induced protection against HER2-expressing tumors.

PMID- 20823151
TI  - AACR special conference on epithelial-mesenchymal transition and cancer
      progression and treatment.
AB  - Epithelial-mesenchymal transition (EMT) is a developmental program implicated in
      cancer progression and was the subject of the 2010 AACR meeting on the topic of
      EMT and Cancer Progression and Treatment held on February 28 to March 2 in
      Arlington, Virginia. A review of the involvement of EMT in gastrulation,
      organogenesis, carcinogenesis, and metastatic progression elucidated the overlap
      of EMT in these physiologic and pathologic conditions. Both novel and traditional
      markers of cells undergoing EMT were discussed and compared with features used to
      define cancer stem cells. Importantly, these defining characteristics of cells
      undergoing EMT were discussed in the context of therapeutic and prognostic
      developments.

PMID- 20823152
TI  - Ligand-independent toll-like receptor signals generated by ectopic overexpression
      of MyD88 generate local and systemic antitumor immunity.
AB  - Although critical for initiating and regulating immune responses, the therapeutic
      use of individual cytokines as anticancer immunotherapeutic agents has achieved
      only modest clinical success. Consequently, many current strategies have focused
      on the use of specific immunotherapeutic agonists that engage individual
      receptors of innate immune networks, such as the Toll-like receptor (TLR) system,
      each resulting in specific patterns of gene expression, cytokine production, and
      inflammatory outcome. However, these immunotherapeutics are constrained by
      variable cellular TLR expression and responsiveness to particular TLR agonists,
      as well as the specific cellular context of different tumors. We hypothesized
      that overexpression of MyD88, a pivotal regulator of multiple TLR signaling
      pathways, could circumvent these constraints and mimic coordinated TLR signaling
      across all cell types in a ligand-independent fashion. To explore this
      hypothesis, we generated an adenoviral vector expressing MyD88 and show that Ad
      MyD88 infection elicits extensive Th1-specific transcriptional and secreted
      cytokine signatures in all murine and human cell types tested in vitro and in
      vivo. Importantly, in vivo intratumoral injection of Ad-MyD88 into established
      tumor masses enhanced adaptive immune responses and inhibited local tumor
      immunosuppression, resulting in significantly inhibited local and systemic growth
      of multiple tumor types. Finally, Ad-MyD88 infection of primary human dendritic
      cells, tumor-associated fibroblasts, and colorectal carcinoma cells elicited
      significant Th1-type cytokine responses, resulting in enhanced tumor cell lysis
      and expansion of human tumor antigen-specific T cells. Thus, Ad-MyD88 initiated
      robust antitumor activity in established murine tumor microenvironments and in
      human contexts, suggesting its potential effectiveness as a clinical
      immunotherapeutic strategy.

PMID- 20823153
TI  - Loss of osteoclasts contributes to development of osteosarcoma pulmonary
      metastases.
AB  - We conducted a transcriptomic screen of osteosarcoma (OS) biopsies and found that
      expression of osteoclast-specific tartrate-resistant acid phosphatase 5
      (ACP5/TRAP) is significantly downregulated in OS compared with nonmalignant bone
      (P < 0.0001). Moreover, lesions from OS patients with pulmonary metastases had 2
      fold less ACP5/TRAP expression (P < 0.018) than lesions from patients without
      metastases. In addition, we found a direct correlation (P = 0.0166) between
      ACP5/TRAP expression and time to metastasis. Therefore, we examined whether
      metastasis-competent (MC) OS cells could induce loss of ACP5(+) osteoclasts and
      contribute to metastasis. We found that MC OS cell lines can inhibit
      osteoclastogenesis in vitro and in vivo. In addition, osteoclasts can inhibit the
      migration of MC OS cells in vitro. Finally, ablation of osteoclasts with
      zoledronic acid increases the number of metastatic lung lesions in an orthotopic
      OS model, whereas fulvestrant treatment increases osteoclast numbers and reduces
      metastatic lesions. These data indicate that the metastatic potential of OS is
      determined early in tumor development and that loss of osteoclasts in the primary
      lesion enhances OS metastasis.

PMID- 20823154
TI  - Angiopoietin-4 promotes glioblastoma progression by enhancing tumor cell
      viability and angiogenesis.
AB  - Glioblastoma multiforme (GBM) is a highly invasive and vascularized aggressive
      brain tumor. Less than 10% of GBM patients survive >5 years after diagnosis.
      Angiogenesis plays an important role in GBM growth, and antiangiogenesis-based
      therapies have shown clinical efficacy for GBM patients. Unfortunately,
      therapeutic resistance often develops in these patients, suggesting that GBM
      cells are capable of switching their dependency on one proangiogenic signaling
      pathway to an alternative one. Therefore, it is important to identify novel
      angiogenic factors that play essential roles in tumor angiogenesis and GBM
      progression. Angiopoietins (Ang-1, Ang-2, and Ang-4) are the ligands of the Tie-2
      receptor tyrosine kinase (RTK). The roles of Ang-1 and Ang-2 in tumor
      angiogenesis have been established. However, little is known about how Ang-4
      affects tumor angiogenesis and GBM progression and the mechanism underlying its
      effects. In our current study, we establish that Ang-4 is upregulated in human
      GBM tissues and cells. We show that, like endothelial cells, human GBM cells
      express Tie-2 RTK. We first establish that Ang-4 promotes in vivo growth of human
      GBM cells by promoting tumor angiogenesis and directly activating extracellular
      signal-regulated kinase 1/2 (Erk1/2) in GBM cells. Our results establish the
      novel effects of Ang-4 on tumor angiogenesis and GBM progression and suggest that
      this pro-GBM effect of Ang-4 is mediated by promoting tumor angiogenesis and
      activating Erk1/2 kinase in GBM cells. Together, our results suggest that the Ang
      4-Tie-2 functional axis is an attractive therapeutic target for GBM.

PMID- 20823155
TI  - The sympathetic nervous system induces a metastatic switch in primary breast
      cancer.
AB  - Metastasis to distant tissues is the chief driver of breast cancer-related
      mortality, but little is known about the systemic physiologic dynamics that
      regulate this process. To investigate the role of neuroendocrine activation in
      cancer progression, we used in vivo bioluminescence imaging to track the
      development of metastasis in an orthotopic mouse model of breast cancer. Stress
      induced neuroendocrine activation had a negligible effect on growth of the
      primary tumor but induced a 30-fold increase in metastasis to distant tissues
      including the lymph nodes and lung. These effects were mediated by beta
      adrenergic signaling, which increased the infiltration of CD11b(+)F4/80(+)
      macrophages into primary tumor parenchyma and thereby induced a prometastatic
      gene expression signature accompanied by indications of M2 macrophage
      differentiation. Pharmacologic activation of beta-adrenergic signaling induced
      similar effects, and treatment of stressed animals with the beta-antagonist
      propranolol reversed the stress-induced macrophage infiltration and inhibited
      tumor spread to distant tissues. The effects of stress on distant metastasis were
      also inhibited by in vivo macrophage suppression using the CSF-1 receptor kinase
      inhibitor GW2580. These findings identify activation of the sympathetic nervous
      system as a novel neural regulator of breast cancer metastasis and suggest new
      strategies for antimetastatic therapies that target the beta-adrenergic induction
      of prometastatic gene expression in primary breast cancers.

PMID- 20823156
TI  - The neutrophil elastase inhibitor elafin triggers rb-mediated growth arrest and
      caspase-dependent apoptosis in breast cancer.
AB  - Elafin, an endogenous inhibitor of neutrophil elastase, is expressed in human
      mammary epithelial cells but is transcriptionally downregulated in breast cancer
      cells. We hypothesized that elafin may exert a tumor-suppressive activity in the
      context of breast cancer. In this study, we show that the retinoblastoma (Rb)
      pathway governs the antitumor properties of elafin. In breast cancer cells with
      functional Rb, the expression of elafin triggered Rb-dependent cell cycle arrest.
      Elafin also exhibited suppressive activity in breast cancer cell lines lacking
      Rb, but this was associated with an induction of caspase-3-dependent, p53
      independent apoptotic cell death. Normal mammary epithelial cells were not
      affected by elafin. Collectively, these results argue that elafin mediates tumor
      suppressive effects that are cytostatic or cytotoxic depending on the Rb status.
      Our findings suggest that elafin could be engineered as a therapeutic modality to
      treat breast cancer without toxicity to normal proliferating cells.

PMID- 20823157
TI  - IFN{gamma} markedly cooperates with intratumoral dendritic cell vaccine in dog
      tumor models.
AB  - Dendritic cell (DC)-based immunotherapy can trigger effective immune responses
      against cancer in human patients. Although accompanied by little toxicity,
      further improvements are needed to optimize immune responses for fully
      satisfactory clinical outcomes. IFNgamma, a potent inducer of T helper type 1
      immune responses, is considered an important tool to realize improvements. In
      this study, we sought to clarify the effect of IFNgamma on the maturation and
      activation of DCs and the clinical outcome of DC-based cancer therapy in dogs. In
      vitro experiments indicated that IFNgamma significantly enhanced the expression
      of immune stimulatory molecules and interleukin-12 by DCs derived from canine
      monocytes. IFNgamma also significantly strengthened DC-mediated growth
      suppression against tumor cell lines. DC inoculation with concomitant delivery of
      IFNgamma into primary or recurrent tumors elicited significant clinical
      responses, including four complete responses and two partial responses against
      malignant tumors, also eliciting partial responses against benign but actively
      growing tumors. Together, our results indicate that combining IFNgamma and DCs
      could induce strong immune responses against tumors, significantly improving
      clinical outcomes. The present study of dogs bearing common types of cancer in
      humans offers a unique line of support for the development of human cancer
      therapies.

PMID- 20823158
TI  - Hyaluronan deficiency in tumor stroma impairs macrophage trafficking and tumor
      neovascularization.
AB  - Despite the importance of stromal cells in tumor progression, our overall
      understanding of the molecular signals that regulate the complex cellular
      interactions within tumor stroma is limited. Here, we provide multiple lines of
      evidence that tumor-associated macrophages (TAM) preferentially traffic to
      stromal areas formed within tumors in a manner dependent on a hyaluronan (HA)
      rich tumor microenvironment. To address the role of stroma-derived HA in
      macrophage recruitment, we disrupted the HA synthase 2 (Has2) gene in stromal
      fibroblasts using conditional gene targeting. The Has2 null fibroblasts showed
      severe impairment in recruiting macrophages when inoculated with tumor cells into
      nude mice, which shows the contribution of stroma-derived HA in intratumoral
      macrophage mobilization. Furthermore, a deficiency in stromal HA attenuated tumor
      angiogenesis and lymphangiogenesis concomitantly with impaired macrophage
      recruitment. Taken together, our results suggest that stromal HA serves as a
      microenvironmental signal for the recruitment of TAMs, which are key regulatory
      cells involved in tumor neovascularization.

PMID- 20823159
TI  - Quantitative imaging of lymphatic function with liposomal indocyanine green.
AB  - Lymphatic vessels play a major role in cancer progression and in postsurgical
      lymphedema, and several new therapeutic approaches targeting lymphatics are
      currently being developed. Thus, there is a critical need for quantitative
      imaging methods to measure lymphatic flow. Indocyanine green (ICG) has been used
      for optical imaging of the lymphatic system, but it is unstable in solution and
      may rapidly enter venous capillaries after local injection. We developed a novel
      liposomal formulation of ICG (LP-ICG), resulting in vastly improved stability in
      solution and an increased fluorescence signal with a shift toward longer
      wavelength absorption and emission. When injected intradermally to mice, LP-ICG
      was specifically taken up by lymphatic vessels and allowed improved visualization
      of deep lymph nodes. In a genetic mouse model of lymphatic dysfunction, injection
      of LP-ICG showed no enhancement of draining lymph nodes and slower clearance from
      the injection site. In mice bearing B16 luciferase-expressing melanomas
      expressing vascular endothelial growth factor-C (VEGF-C), sequential near-IR
      imaging of intradermally injected LP-ICG enabled quantification of lymphatic
      flow. Increased flow through draining lymph nodes was observed in mice bearing
      VEGF-C-expressing tumors without metastases, whereas a decreased flow pattern was
      seen in mice with a higher lymph node tumor burden. This new method will likely
      facilitate quantitative studies of lymphatic function in preclinical
      investigations and may also have potential for imaging of lymphedema or improved
      sentinel lymph detection in cancer.

PMID- 20823160
TI  - Dacarbazine treatment before peptide vaccination enlarges T-cell repertoire
      diversity of melan-a-specific, tumor-reactive CTL in melanoma patients.
AB  - Combination of chemotherapy and immunotherapy to increase the effectiveness of an
      antitumor immune response is currently regarded as an attractive antitumor
      strategy. In a pilot clinical trial, we have recently documented an increase of
      melanoma antigen A (Melan-A)-specific, tumor-reactive, long-lasting effector
      memory CD8(+) T cells after the administration of dacarbazine (DTIC) 1 day before
      peptide vaccination in melanoma patients. Global transcriptional analysis
      revealed a DTIC-induced activation of genes involved in the immune response and
      leukocyte activation. To identify the possible mechanisms underlying this
      improved immune response, we have compared the endogenous and the treatment
      induced anti-Melan-A response at the clonal level in patients treated with the
      vaccine alone or with DTIC plus vaccine. We report a progressive widening of T
      cell receptor (TCR) repertoire diversity, accompanied by high avidity and tumor
      reactivity, only in Melan-A-specific T-cell clones of patients treated with
      chemoimmunotherapy, with a trend toward longer survival. Differently, patients
      treated with vaccine alone showed a tendency to narrowing the TCR repertoire
      diversity, accompanied by a decrease of tumor lytic activity in one patient.
      Collectively, our findings indicate that DTIC plus vaccination shapes the TCR
      repertoire in terms of diversity and antitumor response, suggesting that this
      combined therapy could be effective in preventing melanoma relapse.

PMID- 20823161
TI  - Modifying akt signaling in B-cell chronic lymphocytic leukemia cells.
AB  - Emerging evidence suggests that the survival of B-cell chronic lymphocytic
      leukemia (CLL) cells is dependent on microenvironmental influences such as
      antigenic stimulation and support by stromal cells. Akt, also known as protein
      kinase B, is a central component in prosurvival signaling downstream of these
      events. We investigated the role of Akt and its modulation by the protooncogene T
      cell leukemia 1a (Tcl1a) in the survival pathways of primary CLL samples and CLL
      derived prolymphocytic cell lines MEC-1 and MEC-2. Akt activation was increased
      by the protective presence of human bone marrow stromal cells and B-cell receptor
      mimicking signals but antagonized by direct Akt blockade with the novel specific
      inhibitor AiX, with preferential apoptosis induction in CLL cells with an
      unmutated immunoglobulin status, which predicts poor clinical outcome. In
      addition, we found a direct interaction of Akt with Tcl1a in an endogenous
      coimmunoprecipitation assay. Confirming the critical role of Tcl1a in modulating
      Akt signaling, Akt activation was enhanced by overexpressing Tcl1a in CLL. In
      contrast, decreasing Tcl1a levels by small interfering RNA reduced Akt activation
      in the fludarabine-insensitive CLL cell line MEC-2 and sensitized the malignant
      cells to fludarabine treatment. In summary, our data reveal a significant role
      for the Akt-Tcl1a axis in CLL survival and propose a further evaluation of this
      interplay for targeting chemoresistance phenomena.

PMID- 20823162
TI  - Colorectal tumors are effectively eradicated by combined inhibition of {beta}
      catenin, KRAS, and the oncogenic transcription factor ITF2.
AB  - Colorectal carcinomas (CRC) harbor well-defined genetic abnormalities, including
      aberrant activation of beta-catenin (beta-cat) and KRAS, but independent
      targeting of these molecules seems to have limited therapeutic effect. In this
      study, we report therapeutic effects of combined targeting of different oncogenes
      in CRC. Inducible short hairpin RNA (shRNA)-mediated silencing of beta-cat, ITF2,
      or KRAS decreased proliferation by 88%, 72%, and 45%, respectively, with no
      significant apoptosis in any case. In contrast, combined blockade of beta-cat and
      ITF2 inhibited proliferation by 99% with massive apoptosis. Similar effects
      occurred after combined shRNA against beta-cat and KRAS. In vivo, single oncogene
      blockade inhibited the growth of established tumors by up to 30%, whereas dual
      beta-cat and ITF2 targeting caused 93% inhibition. Similar tumor growth
      suppression was achieved by double beta-cat/KRAS shRNA in vivo. Our findings
      illustrate an effective therapeutic principle in CRC based on a combination
      targeting strategy that includes the ITF2 oncogene, which represents a novel
      therapeutic target.

PMID- 20823163
TI  - Discovery and canine preclinical assessment of a nontoxic procaspase-3-activating
      compound.
AB  - A critical event in the apoptotic cascade is the proteolytic activation of
      procaspases to active caspases. The caspase autoactivating compound PAC-1 induces
      cancer cell apoptosis and exhibits antitumor activity in murine xenograft models
      when administered orally as a lipid-based formulation or implanted s.c. as a
      cholesterol pellet. However, high doses of PAC-1 were found to induce
      neurotoxicity, prompting us to design and assess a novel PAC-1 derivative called
      S-PAC-1. Similar to PAC-1, S-PAC-1 activated procaspase-3 and induced cancer cell
      apoptosis. However, S-PAC-1 did not induce neurotoxicity in mice or dogs.
      Continuous i.v. infusion of S-PAC-1 in dogs led to a steady-state plasma
      concentration of ~10 MUmol/L for 24 to 72 hours. In a small efficacy trial of S
      PAC-1, evaluation of six pet dogs with lymphoma revealed that S-PAC-1 was well
      tolerated and that the treatments induced partial tumor regression or stable
      disease in four of six subjects. Our results support this canine setting for
      further evaluation of small-molecule procaspase-3 activators, including S-PAC-1,
      a compound that is an excellent candidate for further clinical evaluation as a
      novel cancer chemotherapeutic.

PMID- 20823164
TI  - Chemotherapy-induced genotoxic stress promotes sensitivity to natural killer cell
      cytotoxicity by enabling missing-self recognition.
AB  - Natural killer (NK) cells can recognize and kill tumor cells lacking "self"
      markers, such as class I MHC, but the basis for this recognition is not
      completely understood. NKR-P1 receptors are members of the C-type lectin-related
      NK receptor superfamily that are conserved from rodents to humans. Identification
      of Clr ligands for the NKR-P1 receptors has facilitated functional analysis of
      MHC-independent target cell recognition by NK cells. One receptor-ligand pair,
      NKR-P1B:Clr-b, can mediate "missing-self" recognition of tumor and infected
      cells, but the role of this axis in sensing stressed cells remains unknown. Here,
      we show that Clr-b is rapidly downregulated in cells undergoing genotoxic and
      cellular stress at the level of both RNA and surface protein. Stress-mediated
      loss of Clr-b on leukemia cells enhanced cytotoxicity mediated by NKR-P1B(+) NK
      cells. Notably, Clr-b downregulation was coordinated functionally with stress
      mediated upregulation of NKG2D ligands (but not class I MHC). Our findings
      highlight a unique role for the MHC-independent NKR-P1B:Clr-b missing-self axis
      in recognition of stressed cells, and provide evidence of two independent levels
      of Clr-b regulation in stressed cells.

PMID- 20823165
TI  - In vivo imaging of tumor transduced with bimodal lentiviral vector encoding human
      ferritin and green fluorescent protein on a 1.5T clinical magnetic resonance
      scanner.
AB  - A combination of reporter genes for magnetic resonance imaging (MRI) and optical
      imaging can provide an additional level of noninvasive and quantitative
      information about biological processes occurring in deep tissues. We developed a
      bimodal lentiviral vector to monitor deep tissue events using MRI to detect myc
      tagged human ferritin heavy chain (myc-hFTH) expression and fluorescence imaging
      to detect green fluorescent protein (GFP) expression. The transgene construct was
      stably transfected into MCF-7 and F-98 cells. After transplantation of the cells
      expressing myc-hFTH and GFP into mice or rats, serial MRI and fluorescence
      imaging were performed with a human wrist coil on a 1.5T MR scanner and optical
      imaging analyzer for 4 weeks. No cellular toxicity due to overexpression of myc
      hFTH and GFP was observed in MTT and trypan blue exclusion assays. Iron
      accumulation was observed in myc-hFTH cells and tumors by Prussian blue staining
      and iron binding assays. The myc-hFTH cells and tumors had significantly lower
      signal intensities in T(2)-weighted MRI than mock-transfected controls (P <=
      0.05). This is direct evidence that myc-hFTH expression can be visualized
      noninvasively with a 1.5T clinical MR scanner. This study shows that MRI and
      fluorescence imaging of transplanted cells at molecular and cellular levels can
      be performed simultaneously using our bimodal lentiviral vector system. Our
      techniques can be used to monitor tumor growth, metastasis, and regression during
      cell and gene-based therapy in deep tissues.

PMID- 20823167
TI  - Estimated cumulative incidence of pandemic (H1N1) influenza among pregnant women
      during the first wave of the 2009 pandemic.
AB  - BACKGROUND: Hospitalization and lab confirmed cases of H1N1 have been reported
      during the first wave of the 2009 pandemic but these are not accurate measures of
      influenza incidence in the population. We estimated the cumulative incidence of
      pandemic (H1N1) influenza among pregnant women in the province of Manitoba during
      the first wave of the 2009 pandemic. METHODS: Two panels of stored frozen serum
      specimens collected for routine prenatal screening were randomly selected for
      testing before (March 2009, n = 252) and after (August 2009, n = 296) the first
      wave of the pandemic. A standard hemagglutination inhibition assay was used to
      detect the presence of IgG antibodies against the pandemic (H1N1) 2009 virus. The
      cumulative incidence of pandemic (H1N1) influenza was calculated as the
      difference between the point prevalence rates in the first and second panels.
      RESULTS: Of the specimens collected in March, 7.1% were positive for the IgG
      antibodies (serum antibody titre >= 1:40). The corresponding prevalence was 15.7%
      among the specimens collected in August. The difference indicated a cumulative
      incidence of 8.6% (95% confidence interval [CI] 3.2%-13.7%). The rate differed
      geographically, the highest being in the northern regions (20.8%, 95% CI 7.9%
      31.8%), as compared with 4.0% (95% CI 0.0%-11.9%) in Winnipeg and 8.9% (95% CI
      0.0%-18.8%) in the rest of the province. INTERPRETATION: We estimated that the
      cumulative incidence of pandemic (H1N1) influenza among pregnant women in
      Manitoba during the first wave of the 2009 pandemic was 8.6%. It was 20.8% in the
      northern regions of the province.

PMID- 20823169
TI  - Cast versus splint in children with minimally angulated fractures of the distal
      radius: a randomized controlled trial.
AB  - BACKGROUND: Minimally angulated fractures of the distal radius are common in
      children and have excellent outcomes. We conducted a randomized controlled trial
      to determine whether the use of a prefabricated splint is as effective as a cast
      in the recovery of physical function. METHODS: We included 96 children 5 to 12
      years of age who were treated for a minimally angulated (<= 15 degrees )
      greenstick or transverse fracture of the wrist between April 2007 and September
      2009 at a tertiary care pediatric hospital. Participants were randomly assigned
      to receive either a prefabricated wrist splint or a short arm cast for four
      weeks. The primary outcome was physical function at six weeks, measured using the
      performance version of the Activities Scale for Kids. Additional outcomes
      included the degree of angulation, range of motion, grip strength and
      complications. RESULTS: Of the 96 children, 46 received a splint and 50 a cast.
      The mean Activities Scale for Kids score at six weeks was 92.8 in the splint
      group and 91.4 in the cast group (difference 1.44, 95% confidence interval [CI] 
      1.75 to 4.62). Thus, the null hypothesis that the splint is less effective by at
      least seven points was rejected. The between-group difference in angulation at
      four weeks was not statistically significant (9.85 degrees  in the splint group
      and 8.20 degrees  in the cast group; mean difference 1.65 degrees , 95% CI -1.82
      degrees  to 5.11 degrees ), nor was the between-group differences in range of
      motion, grip strength and complications. INTERPRETATION: In children with
      minimally angulated fractures of the distal radius, use of a splint was as
      effective as a cast with respect to the recovery of physical function. In
      addition, the devices were comparable in terms of the maintenance of fracture
      stability and the occurrence of complications. (ClinicalTrials.gov trial register
      no. NCT00610220.).

PMID- 20823170
TI  - Academic branding: erythema ab igne and use of laptop computers.

PMID- 20823171
TI  - Kikuchi-Fujimoto disease: lymphadenopathy in siblings.

PMID- 20823172
TI  - Polluted waterways and physician shortages.

PMID- 20823173
TI  - Reducing infant mortality rate a challenge in Liberia.

PMID- 20823174
TI  - Cadaver shows stir controversy.

PMID- 20823175
TI  - Pregnant and alone in Uganda.

PMID- 20823176
TI  - Continuing medical education programs being placed under closer scrutiny.

PMID- 20823177
TI  - Contribution of lifelong adverse experiences to social health inequalities:
      findings from a population survey in France.
AB  - BACKGROUND: Recent research shows that adverse experiences, such as economic
      hardships or exclusion, contribute to deterioration of health status. However,
      individuals currently experiencing adverse experiences are excluded from
      conventional health surveys, which, in addition, often focus on current social
      situation but rarely address past adverse experiences. This research explores the
      role of such experiences on health and related social inequalities based on a new
      set of ad hoc questions included in a regular health survey. METHODS: In 2004,
      the National Health, Health Care and Insurance Survey included three questions on
      lifelong adverse experiences (LAE): financial difficulties, housing difficulties
      due to financial hardship, isolation. Logistic regressions were used to analyse
      associations between LAE, current socio-economic status (SES) (education,
      occupation, income) and health status (self-perceived health, activity
      limitation, chronic morbidity), on a sample of 4308 men and women aged >=35
      years. RESULTS: LAE were reported by 20% of the sample. They were more frequent
      in low SES groups but concerned >10% of the highest income group. LAE increased
      the risk of poor self-perceived health, diseases and activity limitations, even
      after controlling for current SES [odds ratio (OR) > 2]. LAE experienced only
      during childhood are also linked to health. LAE account for up to 32% of the OR
      of activity limitations associated with the lowest quintile among women and 26%
      among men. CONCLUSIONS: LAE contribute to the social health gradient and explain
      variability within social groups. It is useful to take lifetime social factors
      into account when monitoring health inequalities.

PMID- 20823181
TI  - Assisted death without consent?

PMID- 20823182
TI  - Legislation protects the vulnerable?

PMID- 20823183
TI  - Moving on from euthanasia.

PMID- 20823184
TI  - Moving on from euthanasia.

PMID- 20823185
TI  - Ontario immunization rate for polio.

PMID- 20823186
TI  - Increasing rates of flu vaccination in primary care staff.

PMID- 20823189
TI  - Urine cultures for kids.

PMID- 20823191
TI  - Cardiovascular disease among South Asians.

PMID- 20823192
TI  - The ubiquitin-proteasome system regulates the accumulation of Turnip yellow
      mosaic virus RNA-dependent RNA polymerase during viral infection.
AB  - Replication of positive-strand RNA viruses, the largest group of plant viruses,
      is initiated by viral RNA-dependent RNA polymerase (RdRp). Given its essential
      function in viral replication, understanding the regulation of RdRp is of great
      importance. Here, we show that Turnip yellow mosaic virus (TYMV) RdRp (termed
      66K) is degraded by the proteasome at late time points during viral infection and
      that the accumulation level of 66K affects viral RNA replication in infected
      Arabidopsis thaliana cells. We mapped the cis-determinants responsible for 66K
      degradation within its N-terminal noncatalytic domain, but we conclude that 66K
      is not a natural N-end rule substrate. Instead, we show that a proposed PEST
      sequence within 66K functions as a transferable degradation motif. In addition,
      several Lys residues that constitute target sites for ubiquitylation were mapped;
      mutation of these Lys residues leads to stabilization of 66K. Altogether, these
      results demonstrate that TYMV RdRp is a target of the ubiquitin-proteasome system
      in plant cells and support the idea that proteasomal degradation may constitute
      yet another fundamental level of regulation of viral replication.

PMID- 20823194
TI  - Calpain inhibitor protects cells against light-induced retinal degeneration.
AB  - Calpains are activated by excessive light exposure and related to retinal
      degeneration. We investigated the protective effects of ((1S)-1-((((1S)-1-benzyl
      3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl)carbamic acid 5
      methoxy-3-oxapentyl ester (SNJ-1945), a calpain inhibitor, against light-induced
      retinal degeneration in mice. SNJ-1945 was orally administrated at doses of 100
      and 200 mg/kg at 30 min before and just after light exposure. Light-induced
      calpain activation was evaluated by using proteolysis of alpha-spectrin and p35
      (a neuron-specific activator for cyclin-dependent kinase 5). The effects of SNJ
      1945 against light-induced retinal damage were examined by the thickness of the
      outer nuclear layer (ONL). Photoreceptor apoptosis was assessed by counting
      terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive
      cells in ONL. Retinal functions were measured in terms of a- and b-wave
      amplitudes by using an electroretinogram. As the mechanism of SNJ-1945, caspase
      3/7 measurement was carried out. SNJ-1945 inhibited the proteolysis of alpha
      spectrin and p35 by light exposure and presented a decrease in the numbers of
      TUNEL-positive cells and ONL atrophy. Furthermore, SNJ-1945 presented a decrease
      in a- and b-wave amplitude and caspase-3/7 activation induced by light exposure.
      These findings suggest that the activation of calpain plays a pivotal role in
      photoreceptor degeneration by light exposure, and SNJ-1945 may be a candidate for
      effectively treating diseases related to photoreceptor degeneration.

PMID- 20823193
TI  - Cytokinin regulation of auxin synthesis in Arabidopsis involves a homeostatic
      feedback loop regulated via auxin and cytokinin signal transduction.
AB  - Together, auxin and cytokinin regulate many of the processes that are critical to
      plant growth, development, and environmental responsiveness. We have previously
      shown that exogenous auxin regulates cytokinin biosynthesis in Arabidopsis
      thaliana. In this work, we show that, conversely, the application or induced
      ectopic biosynthesis of cytokinin leads to a rapid increase in auxin biosynthesis
      in young, developing root and shoot tissues. We also show that reducing
      endogenous cytokinin levels, either through the induction of CYTOKININ OXIDASE
      expression or the mutation of one or more of the cytokinin biosynthetic
      ISOPENTENYLTRANSFERASE genes leads to a reduction in auxin biosynthesis.
      Cytokinin modifies the abundance of transcripts for several putative auxin
      biosynthetic genes, suggesting a direct induction of auxin biosynthesis by
      cytokinin. Our data indicate that cytokinin is essential, not only to maintain
      basal levels of auxin biosynthesis in developing root and shoot tissues but also
      for the dynamic regulation of auxin biosynthesis in response to changing
      developmental or environmental conditions. In combination with our previous work,
      the data suggest that a homeostatic feedback regulatory loop involving both auxin
      and cytokinin signaling acts to maintain appropriate auxin and cytokinin
      concentrations in developing root and shoot tissues.

PMID- 20823195
TI  - Magnetic resonance imaging detection and time course of cerebral microhemorrhages
      during passive immunotherapy in living amyloid precursor protein transgenic mice.
AB  - In recent years immunotherapy-based approaches for treating Alzheimer's disease
      have become the subject of intensive research. However, an important mechanistic
      related safety concern is exacerbation of the risk of microhemorrhage that may be
      associated with fast removal of amyloid-beta (Abeta) deposits found in blood
      vessels or brain parenchyma. Rapid in vivo detection of microhemorrhages in
      living amyloid precursor protein transgenic mice has not been described, and
      histological analysis can take several months before this risk is assessed. Aged
      transgenic mice were divided into two groups that would undergo longitudinal
      passive immunotherapy for 12 or 18 weeks. 6G1, a nonselective anti-Abeta
      monoclonal antibody, and 8F5, a more selective antioligomeric Abeta monoclonal
      antibody, were examined in both longitudinal studies. High-resolution T2*
      weighted magnetic resonance microscopy (100 * 100 * 400 MUm) was used for
      microhemorrhage detection in vivo. Cerebral microhemorrhages by magnetic
      resonance imaging were compared with histological hemosiderin staining in each
      animal; results showed that T2*-weighted magnetic resonance microscopy can
      reliably detect microhemorrhages of >=60 MUm in diameter at baseline and after 12
      to 18 weeks of treatment in the same animals in vivo. This correlated
      significantly with histological readings. This new imaging safety biomarker can
      be readily applied to preclinical antibody screening in a longitudinal manner.
      6G1 and 8F5, however, both increased microhemorrhage incidence in aged amyloid
      precursor protein transgenic mice compared with their baseline and vehicle
      treatment. A highly selective antibody for soluble Abeta is needed to address the
      question of whether antibodies that do not bind to deposited Abeta have
      microhemorrhage liability.

PMID- 20823196
TI  - Volaemic assessment of the elderly hyponatraemic patient: reliability of clinical
      assessment and validation of bioelectrical impedance analysis.
AB  - BACKGROUND: Hyponatraemia is the commonest electrolyte disturbance of hospital
      inpatients. Assessment of volaemic status is an important part of diagnosis and
      management. AIM: To determine reliability of clinical assessment of volaemic
      state by assessing inter-observer variability of clinical measures of volaemic
      state. To assess validity of bioelectrical impedance analysis as a tool to
      measure total body water in elderly hyponatraemic patients. DESIGN: Observational
      study conducted in a Department of Medicine for the Elderly. METHODS: Hospital
      inpatients >65 years old (n=22) with serum sodium concentration <130 mmol/l were
      included. Two assessors determined volaemic state on two occasions 72 h apart.
      Level of agreement between observers was determined on each occasion. Total body
      water estimation was undertaken with bioelectrical impedance analysis and
      measurement of dilution of deuterium oxide. Correlation between these two
      measures was then analysed. RESULTS: Cohen's kappa for agreement between two
      observers for overall assessment of volaemic state was 0.59 (P<0.01). Values for
      agreement between individual clinical markers of volaemic state ranged between
      0.16 and 0.45. Pearson correlation coefficient (r) for correlation between
      estimation of total body water undertaken by bioelectrical impedance analysis and
      by measurement of dilution of deuterium oxide was 0.69 (P<0.001). CONCLUSION:
      There was moderate inter-observer agreement of overall clinical volaemic
      assessment of elderly hyponatraemic patients. Total body water estimation by
      bioelectrical impedance analysis correlates well with estimation by measurement
      of dilution of deuterium oxide, providing a potentially useful tool to improve
      the management of the elderly hyponatraemic patient.

PMID- 20823197
TI  - Interleukin-7 (IL-7) treatment accelerates neutrophil recruitment through gamma
      delta T-cell IL-17 production in a murine model of sepsis.
AB  - The sepsis syndrome represents an improper immune response to infection and is
      associated with unacceptably high rates of mortality and morbidity. The
      interactions between T cells and the innate immune system while combating sepsis
      are poorly understood. In this report, we observed that treatment with the
      potent, antiapoptotic cytokine interleukin-7 (IL-7) accelerated neutrophil
      recruitment and improved bacterial clearance. We first determined that T cells
      were necessary for the previously observed IL-7-mediated enhanced survival. Next,
      IL-7 increased Bcl-2 expression in T cells isolated from septic mice as early as
      3 h following treatment. This treatment resulted in increased gamma interferon
      (IFN-gamma) and IP-10 production within the septic peritoneum together with local
      and systemic increases of IL-17 in IL-7-treated mice. We further demonstrate that
      the increase in IL-17 was largely due to increased recruitment and production by
      gammadelta T cells, which express CXCR3. Consistent with increased IL-17
      production, IL-7 treatment increased CXCL1/KC production, neutrophil recruitment,
      and bacterial clearance. Significantly, end-organ tissue injury was not
      significantly different between vehicle- and IL-7-treated mice. Collectively,
      these data illustrate that IL-7 can mediate the cross talk between Th1 and Th17
      lymphocytes during sepsis such that neutrophil recruitment and bacterial
      clearance is improved while early tissue injury is not increased. All together,
      these observations may underlay novel potential therapeutic targets to improve
      the host immune response to sepsis.

PMID- 20823198
TI  - Enteroaggregative Escherichia coli disrupts epithelial cell tight junctions.
AB  - Enteroaggregative Escherichia coli (EAEC) is responsible for inflammatory
      diarrhea in diverse populations, but its mechanisms of pathogenesis have not been
      fully elucidated. We have used a previously characterized polarized intestinal
      T84 cell model to investigate the effects of infection with EAEC strain 042 on
      tight junction integrity. We find that infection with strain 042 induces a
      decrease in transepithelial electrical resistance (TER) compared to uninfected
      controls and to cells infected with commensal E. coli strain HS. When the
      infection was limited after 3 h by washing and application of gentamicin, we
      observed that the TER of EAEC-infected monolayers continued to decline, and they
      remained low even as long as 48 h after the infection. Cells infected with the
      afimbrial mutant strain 042aafA exhibited TER measurements similar to those seen
      in uninfected monolayers, implicating the aggregative adherence fimbriae II
      (AAF/II) as necessary for barrier dysfunction. Infection with wild-type strain
      042 induced aberrant localization of the tight junction proteins claudin-1 and,
      to a lesser degree, occludin. EAEC-infected T84 cells exhibited irregular shapes,
      and some cells became elongated and/or enlarged; these effects were not observed
      after infection with commensal E. coli strain HS or 042aafA. The effects on tight
      junctions were also observed with AAF/I-producing strain JM221, and an afimbrial
      mutant was similarly deficient in inducing barrier dysfunction. Our results show
      that EAEC induces epithelial barrier dysfunction in vitro and implicates the AAF
      adhesins in this phenotype.

PMID- 20823199
TI  - Development of two animal models to study the function of Vibrio parahaemolyticus
      type III secretion systems.
AB  - Vibrio parahaemolyticus is an emerging food- and waterborne pathogen that encodes
      two type III secretion systems (T3SSs). Previous studies have linked type III
      secretion system 1 (T3SS1) to cytotoxicity and T3SS2 to intestinal fluid
      accumulation, but animal challenge models needed to study these phenomena are
      limited. In this study we evaluated the roles of the T3SSs during infection using
      two novel animal models: a model in which piglets were inoculated orogastrically
      and a model in which mice were inoculated in their lungs (intrapulmonarily). The
      bacterial strains employed in this study had equivalent growth rates and beta
      hemolytic activity based on in vitro assays. Inoculation of 48-h-old conventional
      piglets with 10(11) CFU of the wild-type strain (NY-4) or T3SS1 deletion mutant
      strains resulted in acute, self-limiting diarrhea, whereas inoculation with a
      T3SS2 deletion mutant strain failed to produce any clinical symptoms.
      Intrapulmonary inoculation of C57BL/6 mice with the wild-type strain and T3SS2
      deletion mutant strains (5 * 10(5) CFU) induced mortality or a moribund state
      within 12 h (80 to 100% mortality), whereas inoculation with a T3SS1 deletion
      mutant or a T3SS1 T3SS2 double deletion mutant produced no mortality. Bacteria
      were recovered from multiple organs regardless of the strain used in the mouse
      model, indicating that the mice were capable of clearing the lung infection in
      the absence of a functional T3SS1. Because all strains had a similar beta
      hemolysin phenotype, we surmise that thermostable direct hemolysin (TDH) plays a
      limited role in these models. The two models introduced herein produce robust
      results and provide a means to determine how different T3SS1 and T3SS2 effector
      proteins contribute to pathogenesis of V. parahaemolyticus infection.

PMID- 20823200
TI  - The two variants of the Streptococcus pneumoniae pilus 1 RrgA adhesin retain the
      same function and elicit cross-protection in vivo.
AB  - Thirty percent of Streptococcus pneumoniae isolates contain pilus islet 1, coding
      for a pilus composed of the backbone subunit RrgB and two ancillary proteins,
      RrgA and RrgC. RrgA is the major determinant of in vitro adhesion associated with
      pilus 1, is protective in vivo in mouse models, and exists in two variants
      (clades I and II). Mapping of the sequence variability onto the RrgA structure
      predicted from X-ray data showed that the diversity was restricted to the "head"
      of the protein, which contains the putative binding domains, whereas the
      elongated "stalk" was mostly conserved. To investigate whether this variability
      could influence the adhesive capacity of RrgA and to map the regions important
      for binding, two full-length protein variants and three recombinant RrgA portions
      were tested for adhesion to lung epithelial cells and to purified extracellular
      matrix (ECM) components. The two RrgA variants displayed similar binding
      abilities, whereas none of the recombinant fragments adhered at levels comparable
      to those of the full-length protein, suggesting that proper folding and
      structural arrangement are crucial to retain protein functionality. Furthermore,
      the two RrgA variants were shown to be cross-reactive in vitro and cross
      protective in vivo in a murine model of passive immunization. Taken together,
      these data indicate that the region implicated in adhesion and the functional
      epitopes responsible for the protective ability of RrgA may be conserved and that
      the considerable level of variation found within the "head" domain of RrgA may
      have been generated by immunologic pressure without impairing the functional
      integrity of the pilus.

PMID- 20823201
TI  - Epithelial cell-derived S100 calcium-binding proteins as key mediators in the
      hallmark acute neutrophil response during Candida vaginitis.
AB  - Vulvovaginal candidiasis (VVC), caused by Candida species, is a significant
      problem in women of childbearing age. Similar to clinical observations, a robust
      vaginal polymorphonuclear neutrophil (PMN) migration occurs in a subset of mice
      without affecting vaginal fungal burden. We hypothesize that the vaginal PMN
      infiltrate and accompanying inflammation are not protective but instead are
      responsible for the symptoms of infection. The purpose of this study was to
      identify the signal(s) associated with the PMN response in the established mouse
      model. Vaginal lavage fluid from inoculated mice were categorized base on PMN
      counts, evaluated for PMN chemotactic activity and analyzed by SDS-PAGE and mass
      spectrometry (MS) for unique protein identification. The lavage fluid from
      inoculated mice with high, but not low, PMN levels showed increased chemotactic
      activity. Likewise, SDS-PAGE of lavage fluid with high PMN levels showed distinct
      protein patterns. MS revealed that bands at 6 and 14 kDa matched the PMN
      chemotactic calcium-binding proteins (CBPs), S100A8 and S100A9, respectively. The
      presence of the CBPs in lavage fluid was confirmed by Western blots and enzyme
      linked immunosorbent assay. Vaginal tissues and epithelial cells from inoculated
      mice with high PMN levels stained more intensely and exhibited increased mRNA
      transcripts for both proteins compared to those in mice with low PMN levels.
      Subsequent antibody neutralization showed significant abrogation of the
      chemotactic activity when the lavage fluid was treated with anti-S100A8, but not
      anti-S100A9, antibodies. These results reveal that the PMN chemotactic CBP S100A8
      and S100A9 are produced by vaginal epithelial cells following interaction with
      Candida and that S100A8 is a strong candidate responsible for the robust PMN
      migration during experimental VVC.

PMID- 20823202
TI  - Inadequate binding of immune regulator factor H is associated with sensitivity of
      Borrelia lusitaniae to human complement.
AB  - Spirochetes belonging to the Borrelia burgdorferi sensu lato complex differ in
      resistance to complement-mediated killing by human serum. Here, we characterize
      complement sensitivity of a panel of B. lusitaniae isolates derived from ticks
      collected in Germany and Portugal as well as one patient-derived isolate, PoHL.
      All isolates are highly susceptible to complement-mediated lysis in human serum
      and activate complement predominantly by the alternative pathway, leading to an
      increased deposition of complement components C3, C6, and the terminal complement
      complex. Interestingly, serum-sensitive B. lusitaniae isolates were able to bind
      immune regulator factor H (CFH), and some strains also bound CFH-related protein
      1 (CFHR1) and CFHR2. Moreover, CFH bound to the surface of B. lusitaniae was
      inefficient in mediating C3b conversion. Furthermore, the identification and
      characterization of a potential CFH-binding protein, OspE, revealed that this
      molecule possesses a significantly reduced binding capacity for CFH compared to
      that of CFH-binding OspE paralogs expressed by various serum-resistant Borrelia
      species. This finding suggests that a reduced binding capability of CFH is
      associated with an increased serum sensitivity of B. lusitaniae to human
      complement.

PMID- 20823203
TI  - In vivo discrimination of type 3 secretion system-positive and -negative
      Pseudomonas aeruginosa via a caspase-1-dependent pathway.
AB  - Microbe-associated molecular patterns are recognized by Toll-like receptors of
      the innate immune system. This recognition enables a rapid response to potential
      pathogens but does not clearly provide a way for the innate immune system to
      discriminate between virulent and avirulent microbes. We find that pulmonary
      infection of mice with type 3 translocation-competent Pseudomonas aeruginosa
      triggers a rapid inflammatory response, while infection with isogenic
      translocation-deficient mutants does not. Discrimination between translocon
      positive and -negative bacteria requires caspase-1 activity in bone marrow
      derived cells and interleukin-1 receptor signaling. Thus, the activation of
      caspase-1 by bacteria expressing type 3 secretion systems allows for rapid
      recognition of bacteria expressing conserved functions associated with virulence.

PMID- 20823204
TI  - Characterization of toxin plasmids in Clostridium perfringens type C isolates.
AB  - Clostridium perfringens type C isolates cause enteritis necroticans in humans or
      necrotizing enteritis and enterotoxemia in domestic animals. Type C isolates
      always produce alpha toxin and beta toxin but often produce additional toxins,
      e.g., beta2 toxin or enterotoxin. Since plasmid carriage of toxin-encoding genes
      has not been systematically investigated for type C isolates, the current study
      used Southern blot hybridization of pulsed-field gels to test whether several
      toxin genes are plasmid borne among a collection of type C isolates. Those
      analyses revealed that the surveyed type C isolates carry their beta toxin
      encoding gene (cpb) on plasmids ranging in size from ~65 to ~110 kb. When present
      in these type C isolates, the beta2 toxin gene localized to plasmids distinct
      from the cpb plasmid. However, some enterotoxin-positive type C isolates appeared
      to carry their enterotoxin-encoding cpe gene on a cpb plasmid. The tpeL gene
      encoding the large clostridial cytotoxin was localized to the cpb plasmids of
      some cpe-negative type C isolates. The cpb plasmids in most surveyed isolates
      were found to carry both IS1151 sequences and the tcp genes, which can mediate
      conjugative C. perfringens plasmid transfer. A dcm gene, which is often present
      near C. perfringens plasmid-borne toxin genes, was identified upstream of the cpb
      gene in many type C isolates. Overlapping PCR analyses suggested that the toxin
      encoding plasmids of the surveyed type C isolates differ from the cpe plasmids of
      type A isolates. These findings provide new insight into plasmids of proven or
      potential importance for type C virulence.

PMID- 20823205
TI  - Critical role for the host GTPase-activating protein ARAP2 in InlB-mediated entry
      of Listeria monocytogenes.
AB  - The bacterial pathogen Listeria monocytogenes causes food-borne illnesses
      culminating in gastroenteritis, meningitis, or abortion. Listeria induces its
      internalization into some mammalian cells through binding of the bacterial
      surface protein InlB to the host receptor tyrosine kinase Met. Interaction of
      InlB with the Met receptor elicits host downstream signaling pathways that
      promote F-actin cytoskeletal changes responsible for pathogen engulfment. Here we
      show that the mammalian signaling protein ARAP2 plays a critical role in
      cytoskeletal remodeling and internalization of Listeria. Depletion of ARAP2
      through RNA interference (RNAi) caused a marked inhibition of InlB-mediated F
      actin rearrangements and bacterial entry. ARAP2 contains multiple functional
      domains, including a GTPase-activating protein (GAP) domain that antagonizes the
      GTPase Arf6 and a domain capable of binding the GTPase RhoA. Genetic data
      indicated roles for both the Arf GAP and RhoA binding domains in Listeria entry.
      Experiments involving Arf6 RNAi or a constitutively activated allele of Arf6
      demonstrated that one of the ways in which ARAP2 promotes bacterial uptake is by
      restraining the activity of Arf6. Conversely, Rho activity was dispensable for
      Listeria internalization, suggesting that the RhoA binding domain in ARAP2 acts
      by engaging a host ligand other than Rho proteins. Collectively, our findings
      indicate that ARAP2 promotes InlB-mediated entry of Listeria, in part, by
      antagonizing the host GTPase Arf6.

PMID- 20823206
TI  - Branched-chain fatty acids promote Listeria monocytogenes intracellular infection
      and virulence.
AB  - Anteiso-branched-chain fatty acids (BCFA) represent the dominant group of
      membrane fatty acids and have been established as crucial determinants in
      resistance against environmental stresses in Listeria monocytogenes, a
      facultative intracellular pathogen. Here, we investigate the role of anteiso-BCFA
      in L. monocytogenes virulence by using mutants deficient in branched-chain alpha
      keto acid dehydrogenase (BKD), an enzyme complex involved in the synthesis of
      BCFA. In tissue culture models of infection, anteiso-BCFA contributed to
      intracellular growth and survival in macrophages and significantly enhanced
      plaque formation upon prolonged infection in L2 fibroblasts. The intracellular
      defects observed could be attributed partially to insufficient listeriolysin O
      (LLO) production, indicating a requirement for anteiso-BCFA in regulating
      virulence factor production. In a murine model of infection, the BKD-deficient
      mutant was highly attenuated, further emphasizing the importance of BKD-mediated
      metabolism in L. monocytogenes virulence. This study demonstrates an
      underappreciated role for BCFA in bacterial pathogenesis, which may provide
      insight into the development and application of antimicrobial agents.

PMID- 20823207
TI  - OI-57, a genomic island of Escherichia coli O157, is present in other
      seropathotypes of Shiga toxin-producing E. coli associated with severe human
      disease.
AB  - Strains of Shiga toxin-producing Escherichia coli (STEC) are a heterogeneous E.
      coli group that may cause severe disease in humans. STEC have been categorized
      into seropathotypes (SPTs) based on their phenotypic and molecular
      characteristics and the clinical features of the associated diseases. SPTs range
      from A to E, according to a decreasing rank of pathogenicity. To define the
      virulence gene asset ("virulome") characterizing the highly pathogenic SPTs, we
      used microarray hybridization to compare the whole genomes of STEC belonging to
      SPTs B, C, and D with that of STEC O157 (SPT A). The presence of the open reading
      frames (ORFs) associated with SPTs A and B was subsequently investigated by PCR
      in a larger panel of STEC and in other E. coli strains. A genomic island termed
      OI-57 was present in SPTs A and B but not in the other SPTs. OI-57 harbors the
      putative virulence gene adfO, encoding a factor enhancing the adhesivity of STEC
      O157, and ckf, encoding a putative killing factor for the bacterial cell. PCR
      analyses showed that OI-57 was present in its entirety in the majority of the
      STEC genomes examined, indicating that it represents a stable acquisition of the
      positive clonal lineages. OI-57 was also present in a high proportion of the
      human enteropathogenic E. coli genomes assayed, suggesting that it could be
      involved in the attaching-and-effacing colonization of the intestinal mucosa. In
      conclusion, OI-57 appears to be part of the virulome of pathogenic STEC and
      further studies are needed to elucidate its role in the pathogenesis of STEC
      infections.

PMID- 20823208
TI  - Listeria monocytogenes PrsA2 is required for virulence factor secretion and
      bacterial viability within the host cell cytosol.
AB  - In the course of establishing its replication niche within the cytosol of
      infected host cells, the facultative intracellular bacterial pathogen Listeria
      monocytogenes must efficiently regulate the secretion and activity of multiple
      virulence factors. L. monocytogenes encodes two predicted posttranslocation
      secretion chaperones, PrsA1 and PrsA2, and evidence suggests that PrsA2 has been
      specifically adapted for bacterial pathogenesis. PrsA-like chaperones have been
      identified in a number of Gram-positive bacteria, where they are reported to
      function at the bacterial membrane-cell wall interface to assist in the folding
      of proteins translocated across the membrane; in some cases, these proteins have
      been found to be essential for bacterial viability. In this study, the
      contributions of PrsA2 and PrsA1 to L. monocytogenes growth and protein secretion
      were investigated in vitro and in vivo. Neither PrsA2 nor PrsA1 was found to be
      essential for L. monocytogenes growth in broth culture; however, optimal
      bacterial viability was found to be dependent upon PrsA2 for L. monocytogenes
      located within the cytosol of host cells. Proteomic analyses of prsA2 mutant
      strains in the presence of a mutationally activated allele of the virulence
      regulator PrfA revealed a critical requirement for PrsA2 activity under
      conditions of PrfA activation, an event which normally takes place within the
      host cell cytosol. Despite a high degree of amino acid similarity, no detectable
      degree of functional overlap was observed between PrsA2 and PrsA1. Our results
      indicate a critical requirement for PrsA2 under conditions relevant to host cell
      infection.

PMID- 20823209
TI  - Small molecule inhibitors of LcrF, a Yersinia pseudotuberculosis transcription
      factor, attenuate virulence and limit infection in a murine pneumonia model.
AB  - LcrF (VirF), a transcription factor in the multiple adaptational response (MAR)
      family, regulates expression of the Yersinia type III secretion system (T3SS).
      Yersinia pseudotuberculosis lcrF-null mutants showed attenuated virulence in
      tissue culture and animal models of infection. Targeting of LcrF offers a novel,
      antivirulence strategy for preventing Yersinia infection. A small molecule
      library was screened for inhibition of LcrF-DNA binding in an in vitro assay. All
      of the compounds lacked intrinsic antibacterial activity and did not demonstrate
      toxicity against mammalian cells. A subset of these compounds inhibited T3SS
      dependent cytotoxicity of Y. pseudotuberculosis toward macrophages in vitro. In a
      murine model of Y. pseudotuberculosis pneumonia, two compounds significantly
      reduced the bacterial burden in the lungs and afforded a dramatic survival
      advantage. The MAR family of transcription factors is well conserved, with
      members playing central roles in pathogenesis across bacterial genera; thus, the
      inhibitors could have broad applicability.

PMID- 20823210
TI  - Multiple antigen peptide vaccines against Plasmodium falciparum malaria.
AB  - The multiple antigen peptide (MAP) approach is an effective method to chemically
      synthesize and deliver multiple T-cell and B-cell epitopes as the constituents of
      a single immunogen. Here we report on the design, chemical synthesis, and
      immunogenicity of three Plasmodium falciparum MAP vaccines that incorporated
      antigenic epitopes from the sporozoite, liver, and blood stages of the life
      cycle. Antibody and cellular responses were determined in three inbred (C57BL/6,
      BALB/c, and A/J) strains, one congenic (HLA-A2 on the C57BL/6 background) strain,
      and one outbred strain (CD1) of mice. All three MAPs were immunogenic and induced
      both antibody and cellular responses, albeit in a somewhat genetically restricted
      manner. Antibodies against MAP-1, MAP-2, and MAP-3 had an antiparasite effect
      that was also dependent on the mouse major histocompatibility complex background.
      Anti-MAP-1 (CSP-based) antibodies blocked the invasion of HepG2 liver cells by P.
      falciparum sporozoites (highest, 95.16% in HLA-A2 C57BL/6; lowest, 11.21% in
      BALB/c). Furthermore, antibodies generated following immunizations with the MAP-2
      (PfCSP, PfLSA-1, PfMSP-1(42), and PfMSP-3b) and MAP-3 (PfRAP-1, PfRAP-2, PfSERA,
      and PfMSP-1(42)) vaccines were able to reduce the growth of blood stage parasites
      in erythrocyte cultures to various degrees. Thus, MAP-based vaccines remain a
      viable option to induce effective antibody and cellular responses. These results
      warrant further development and preclinical and clinical testing of the next
      generation of candidate MAP vaccines that are based on the conserved protective
      epitopes from Plasmodium antigens that are widely recognized by populations of
      divergent HLA types from around the world.

PMID- 20823211
TI  - Mannheimia haemolytica and its leukotoxin cause neutrophil extracellular trap
      formation by bovine neutrophils.
AB  - Mannheimia haemolytica is an important member of the bovine respiratory disease
      complex, which is characterized by abundant neutrophil infiltration into the
      alveoli and fibrin deposition. Recently several authors have reported that human
      neutrophils release neutrophil extracellular traps (NETs), which are protein
      studded DNA matrices capable of trapping and killing pathogens. Here, we
      demonstrate that the leukotoxin (LKT) of M. haemolytica causes NET formation by
      bovine neutrophils in a CD18-dependent manner. Using an unacylated, noncytotoxic
      pro-LKT produced by an DeltalktC mutant of M. haemolytica, we show that binding
      of unacylated pro-LKT stimulates NET formation despite a lack of cytotoxicity.
      Inhibition of LKT binding to the CD18 chain of lymphocyte function-associated
      antigen 1 (LFA-1) on bovine neutrophils reduced NET formation in response to LKT
      or M. haemolytica cells. Further investigation revealed that NETs formed in
      response to M. haemolytica are capable of trapping and killing a portion of the
      bacterial cells. NET formation was confirmed by confocal microscopy and by
      scanning and transmission electron microscopy. Prior exposure of bovine
      neutrophils to LKT enhanced subsequent trapping and killing of M. haemolytica
      cells in bovine NETs. Understanding NET formation in response to M. haemolytica
      and its LKT provides a new perspective on how neutrophils contribute to the
      pathogenesis of bovine respiratory disease.

PMID- 20823212
TI  - Human conjunctival transcriptome analysis reveals the prominence of innate
      defense in Chlamydia trachomatis infection.
AB  - Trachoma is the leading infectious cause of blindness and is endemic in 52
      countries. There is a critical need to further our understanding of the host
      response during disease and infection, as millions of individuals are still at
      risk of developing blinding sequelae. Infection of the conjunctival epithelial
      cells by the causative bacterium, Chlamydia trachomatis, stimulates an acute host
      response. The main clinical feature is a follicular conjunctivitis that is
      incompletely defined at the tissue-specific gene expression and molecular levels.
      To explore the features of disease and the response to infection, we measured
      host gene expression in conjunctival samples from Gambian children with active
      trachoma and healthy controls. Genome-wide expression and transcription network
      analysis identified signatures characteristic of the expected infiltrating immune
      cell populations, such as neutrophils and T/B lymphocytes. The expression
      signatures were also significantly enriched for genes in pathways which regulate
      NK cell activation and cytotoxicity, antigen processing and presentation,
      chemokines, cytokines, and cytokine receptors. The data suggest that in addition
      to polymorph and adaptive cellular responses, NK cells may contribute to a
      significant component of the conjunctival inflammatory response to chlamydial
      infection.

PMID- 20823213
TI  - The chemokine receptor CXCR2 ligand KC (CXCL1) mediates neutrophil recruitment
      and is critical for development of experimental Lyme arthritis and carditis.
AB  - Deletion of the chemokine receptor CXCR2 prevents the recruitment of neutrophils
      into tissues and subsequent development of experimental Lyme arthritis. Following
      footpad inoculation of Borrelia burgdorferi, the agent of Lyme disease,
      expression of the CXCR2 ligand KC (CXCL1) is highly upregulated in the joints of
      arthritis-susceptible mice and is likely to play an important role in the
      recruitment of neutrophils to the site of infection. To test this hypothesis, we
      infected C3H KC(-/-) mice with B. burgdorferi and followed the development of
      arthritis and carditis. Ankle swelling was significantly attenuated during the
      peak of arthritis in the KC(-/-) mice. Arthritis severity scores were
      significantly lower in the KC(-/-) mice on days 11 and 21 postinfection, with
      fewer neutrophils present in the inflammatory lesions. Cardiac lesions were also
      significantly decreased in KC(-/-) mice at day 21 postinfection. There were,
      however, no differences between C3H wild-type and KC(-/-) mice in spirochete
      clearance from tissues. Two other CXCR2 ligands, LIX (CXCL5) and MIP-2 (CXCL2),
      were not increased to compensate for the loss of KC, and the production of
      several innate cytokines was unaltered. These results demonstrate that KC plays a
      critical nonredundant role in the development of experimental Lyme arthritis and
      carditis via CXCR2-mediated recruitment of neutrophils into the site of
      infection.

PMID- 20823214
TI  - Hierarchical, domain type-specific acquisition of antibodies to Plasmodium
      falciparum erythrocyte membrane protein 1 in Tanzanian children.
AB  - Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a variant
      antigen expressed on the surface of malaria-infected erythrocytes. PfEMP1
      attaches to the vascular lining and allows infected erythrocytes to avoid
      filtration through the spleen. Each parasite genome encodes about 60 different
      PfEMP1 variants, each PfEMP1 comprises several domains in its extracellular
      region, and the PfEMP1 repertoire in different parasites contains domain types
      that are serologically cross-reactive. In this longitudinal study, we followed
      672 children living in an area of high malaria transmission during the first
      years of life and compared the acquisitions of antibodies to 32 Duffy-binding
      ligand-like (DBL) domains representing different types. For each child, we
      determined whether an antibody response to each domain was acquired before,
      after, or at the same time as responses to each of the other domains. We next
      used this information to calculate population-level odds ratios to measure the
      odds that antibodies to a given domain were acquired before antibodies to other
      domains. Odds ratios for 269 of the 496 possible domain combinations were
      statistically significant. Thus, the sequence in which individuals acquire
      antibodies to different PfEMP1 domains is ordered, and children in areas of
      endemicity first acquire antibodies to particular PfEMP1 domains encoded by the
      so-called group A and B/A var genes. The results imply that anti-PfEMP1
      antibodies effectively structure PfEMP1 expression and play a major role in
      limiting parasite multiplication in the blood.

PMID- 20823215
TI  - Fusobacterium nucleatum outer membrane proteins Fap2 and RadD induce cell death
      in human lymphocytes.
AB  - Bacterially induced cell death in human lymphocytes is an important virulence
      factor for pathogenic bacteria. Previously discovered mechanisms of bacterially
      induced cell death are predominantly based on the transfer of bacterial proteins
      to the target host cell, such as the toxins secreted through type I, II, and VI
      secretion systems or effector proteins injected through type III, IV, and Vb
      secretion systems. Here, we report a mechanism employed by the Gram-negative oral
      pathogen Fusobacterium nucleatum for cell death induction of human lymphocytes
      via two outer membrane proteins (OMPs), Fap2 and RadD, which share regions
      homologous to autotransporter secretion systems (type Va secretion systems).
      Genetic and physiological studies established that inactivation of the two OMPs
      led to significantly reduced ability to trigger cell death in Jurkat cells, while
      the corresponding double mutant was almost completely attenuated. Additional
      biochemical and molecular analyses demonstrated that cell-free F. nucleatum
      membranes are sufficient to induce cell death in Jurkat cells, suggesting that no
      active process or effector protein transfer was necessary to induce eukaryotic
      cell death.

PMID- 20823216
TI  - Pro-sustainability choices and child deaths averted: from project experience to
      investment strategy.
AB  - The pursuit of the Millennium Development Goals and advancing the 'global health
      agenda' demand the achievement of health impact at scale through efficient
      investments. We have previously offered that sustainability-a necessary condition
      for successful expansion of programmes-can be addressed in practical terms. Based
      on benchmarks from actual child survival projects, we assess the expected impact
      of translating pro-sustainability choices into investment strategies. We review
      the experience of Save the Children US in Guinea in terms of investment, approach
      to sustainability and impact. It offers three benchmarks for impact: Entry
      project (21 lives saved of children under age five per US$100 000), Expansion
      project (37 LS/US$100k), and Continuation project (100 LS/US$100k). Extrapolating
      this experience, we model the impact of a traditional investment scenario against
      a pro-sustainability scenario and compare the deaths averted per dollar spent
      over five project cycles. The impact per dollar spent on a pro-sustainability
      strategy is 3.4 times that of a traditional one over the long run (range from 2.2
      to 5.7 times in a sensitivity analysis). This large efficiency differential
      between two investment approaches offers a testable hypothesis for large
      scale/long-term studies. The 'bang for the buck' of health programmes could be
      greatly increased by following a pro-sustainability investment strategy.

PMID- 20823217
TI  - Comparison of unrestrained plethysmography and forced oscillation for identifying
      genetic variability of airway responsiveness in inbred mice.
AB  - Lung function detection in mice is currently most accurately measured by invasive
      techniques, which are costly, labor intensive, and terminal. This limits their
      use for large-scale or longitudinal studies. Noninvasive assays are often used
      instead, but their accuracy for measuring lung function parameters such as
      resistance and elastance has been questioned in studies involving small numbers
      of mouse strains. Here we compared parameters detected by two different methods
      using 29 inbred mouse strains: enhanced pause (Penh), detected by unrestrained
      plethysmography, and central airway resistance and lung elastance, detected by a
      forced oscillation technique. We further tested whether the phenotypic variations
      were determined by the same genomic location in genome-wide association studies
      using a linear mixed model algorithm. Penh, resistance, and elastance were
      measured in nonexposed mice or mice exposed to saline and increasing doses of
      aerosolized methacholine. Because Penh differed from airway resistance in several
      strains and because the peak genetic associations found for Penh, resistance, or
      elastance were located at different genomic regions, we conclude that using Penh
      as an indicator for lung function changes in high-throughput genetic studies
      (i.e., genome-wide association studies or quantitative trait locus studies)
      measures something fundamentally different than airway resistance and lung
      elastance.

PMID- 20823218
TI  - Tethered agonist analogs as site-specific probes for domains of the human alpha7
      nicotinic acetylcholine receptor that differentially regulate activation and
      desensitization.
AB  - Homomeric alpha7 nicotinic acetylcholine receptors represent an important and
      complex pharmaceutical target. They can be activated by structurally diverse
      agonists and are highly likely to enter and remain in desensitized states at
      rates determined by the structures of the agonists. To identify structural
      elements regulating this function, we introduced reactive cysteines into the
      alpha7 ligand-binding domain allowing us to bind sulfhydryl-reactive (SH) agonist
      analogs or control reagents onto specific positions in the ligand binding domain.
      We identified four alpha7 mutants (S36C, L38C, W55C, and L119C) in which the
      tethering of the SH reagents blocked further acetylcholine-evoked activation of
      the receptor. However, after selective reaction with SH agonist analogs, the type
      II allosteric modulator N-(5-chloro-2,4-dimethoxyphenyl)-N'-(5-methyl-3
      isoxazolyl-3-isoxazolyl)-urea (PNU-120596) could reactivate L119C and W55C
      mutants and receptors with a reduced or modified C-loop. Modified S36C and L38C
      mutants were insensitive to reactivation by PNU-120596, whether they were reacted
      with agonist analogs or alternative SH reagents. Molecular modeling showed that
      in the W55C and L119C mutants, the ammonium pharmacophore of the agonist analog
      methanethiosulfonate-ethyltrimethylammonium would be in a similar but
      nonidentical position underneath the C-loop. The orientation assumed by the
      ligand tethered to 119C was approximately 3-fold more sensitive to PNU-120596
      than the alternative pose at 55C. Our results support the hypothesis that a
      single ligand can bind within the receptor in different ways and, depending on
      the specific binding pose, may variously promote activation or desensitization,
      or, alternatively, function as a competitive antagonist. This insight may provide
      a new approach for drug development.

PMID- 20823219
TI  - Targeting botulinum neurotoxin persistence by the ubiquitin-proteasome system.
AB  - Botulinum neurotoxins (BoNTs) are the most potent natural toxins known. The
      effects of BoNT serotype A (BoNT/A) can last several months, whereas the effects
      of BoNT serotype E (BoNT/E), which shares the same synaptic target, synaptosomal
      associated protein 25 (SNAP25), last only several weeks. The long-lasting effects
      or persistence of BoNT/A, although desirable for therapeutic applications,
      presents a challenge for medical treatment of BoNT intoxication. Although the
      mechanisms for BoNT toxicity are well known, little is known about the mechanisms
      that govern the persistence of the toxins. We show that the recombinant catalytic
      light chain (LC) of BoNT/E is ubiquitylated and rapidly degraded in cells. In
      contrast, BoNT/A LC is considerably more stable. Differential susceptibility of
      the catalytic LCs to ubiquitin-dependent proteolysis therefore might explain the
      differential persistence of BoNT serotypes. In this regard we show that TRAF2, a
      RING finger protein implicated in ubiquitylation, selectively associates with
      BoNT/E LC and promotes its proteasomal degradation. Given these data, we asked
      whether BoNT/A LC could be targeted for rapid proteasomal degradation by
      redirecting it to characterized ubiquitin ligase domains. We describe chimeric
      SNAP25-based ubiquitin ligases that target BoNT/A LC for degradation, reducing
      its duration in a cellular model for toxin persistence.

PMID- 20823220
TI  - Rigid amphipathic fusion inhibitors, small molecule antiviral compounds against
      enveloped viruses.
AB  - Antiviral drugs targeting viral proteins often result in prompt selection for
      resistance. Moreover, the number of viral targets is limited. Novel antiviral
      targets are therefore needed. The unique characteristics of fusion between virion
      envelopes and cell membranes may provide such targets. Like all fusing bilayers,
      viral envelopes locally adopt hourglass-shaped stalks during the initial stages
      of fusion, a process that requires local negative membrane curvature. Unlike
      cellular vesicles, however, viral envelopes do not redistribute lipids between
      leaflets, can only use the energy released by virion proteins, and fuse to the
      extracellular leaflets of cell membranes. Enrichment in phospholipids with
      hydrophilic heads larger than their hydrophobic tails in the convex outer leaflet
      of vesicles favors positive curvature, therefore increasing the activation energy
      barrier for fusion. Such phospholipids can increase the activation barrier beyond
      the energy provided by virion proteins, thereby inhibiting viral fusion. However,
      phospholipids are not pharmacologically useful. We show here that a family of
      synthetic rigid amphiphiles of shape similar to such phospholipids, RAFIs (rigid
      amphipathic fusion inhibitors), inhibit the infectivity of several otherwise
      unrelated enveloped viruses, including hepatitis C and HSV-1 and -2 (lowest
      apparent IC(50) 48 nM), with no cytotoxic or cytostatic effects (selectivity
      index > 3,000) by inhibiting the increased negative curvature required for the
      initial stages of fusion.

PMID- 20823221
TI  - NMDA receptors regulate GABAA receptor lateral mobility and clustering at
      inhibitory synapses through serine 327 on the gamma2 subunit.
AB  - Modification of the number of GABA(A) receptors (GABA(A)Rs) clustered at
      inhibitory synapses can regulate inhibitory synapse strength with important
      implications for information processing and nervous system plasticity and
      pathology. Currently, however, the mechanisms that regulate the number of
      GABA(A)Rs at synapses remain poorly understood. By imaging superecliptic pHluorin
      tagged GABA(A)R subunits we show that synaptic GABA(A)R clusters are normally
      stable, but that increased neuronal activity upon glutamate receptor (GluR)
      activation results in their rapid and reversible dispersal. This dispersal
      correlates with increases in the mobility of single GABA(A)Rs within the clusters
      as determined using single-particle tracking of GABA(A)Rs labeled with quantum
      dots. GluR-dependent dispersal of GABA(A)R clusters requires Ca(2+) influx via
      NMDA receptors (NMDARs) and activation of the phosphatase calcineurin. Moreover,
      the dispersal of GABA(A)R clusters and increased mobility of individual GABA(A)Rs
      are dependent on serine 327 within the intracellular loop of the GABA(A)R gamma2
      subunit. Thus, NMDAR signaling, via calcineurin and a key GABA(A)R
      phosphorylation site, controls the stability of synaptic GABA(A)Rs, with
      important implications for activity-dependent control of synaptic inhibition and
      neuronal plasticity.

PMID- 20823222
TI  - Identification of a gene essential for protoporphyrinogen IX oxidase activity in
      the cyanobacterium Synechocystis sp. PCC6803.
AB  - Protoporphyrinogen oxidase (Protox) catalyses the oxidation of protoporphyrinogen
      IX to protoporphyrin IX during the synthesis of tetrapyrrole molecules. Protox is
      encoded by the hemY gene in eukaryotes and by the hemG gene in many gamma
      proteobacteria, including Escherichia coli. It has been suggested that other
      bacteria possess a yet unidentified type of Protox. To identify a unique
      bacterial gene encoding Protox, we first introduced the Arabidopsis hemY gene
      into the genome of the cyanobacterium, Synechocystis sp. PCC6803. We subsequently
      mutagenized the cells by transposon tagging and screened the tagged lines for
      mutants that were sensitive to acifluorfen, which is a specific inhibitor of the
      hemY-type Protox. Several cell lines containing the tagged slr1790 locus
      exhibited acifluorfen sensitivity. The slr1790 gene encodes a putative membrane
      spanning protein that is distantly related to the M subunit of NADH dehydrogenase
      complex I. We attempted to disrupt this gene in the wild-type background of
      Synechocystis, but we were only able to obtain heteroplasmic disruptants. These
      cells accumulated a substantial amount of protoporphyrin IX, suggesting that the
      slr1790 gene is essential for growth and Protox activity of cells. We found that
      most cyanobacteria and many other bacteria possess slr1790 homologs. We
      overexpressed an slr1790 homolog of Rhodobacter sphaeroides in Escherichia coli
      and found that this recombinant protein possesses Protox activity in vitro. These
      results collectively demonstrate that slr1790 encodes a unique Protox enzyme and
      we propose naming the slr1790 gene "hemJ."

PMID- 20823223
TI  - High income improves evaluation of life but not emotional well-being.
AB  - Recent research has begun to distinguish two aspects of subjective well-being.
      Emotional well-being refers to the emotional quality of an individual's everyday
      experience--the frequency and intensity of experiences of joy, stress, sadness,
      anger, and affection that make one's life pleasant or unpleasant. Life evaluation
      refers to the thoughts that people have about their life when they think about
      it. We raise the question of whether money buys happiness, separately for these
      two aspects of well-being. We report an analysis of more than 450,000 responses
      to the Gallup-Healthways Well-Being Index, a daily survey of 1,000 US residents
      conducted by the Gallup Organization. We find that emotional well-being (measured
      by questions about emotional experiences yesterday) and life evaluation (measured
      by Cantril's Self-Anchoring Scale) have different correlates. Income and
      education are more closely related to life evaluation, but health, care giving,
      loneliness, and smoking are relatively stronger predictors of daily emotions.
      When plotted against log income, life evaluation rises steadily. Emotional well
      being also rises with log income, but there is no further progress beyond an
      annual income of ~$75,000. Low income exacerbates the emotional pain associated
      with such misfortunes as divorce, ill health, and being alone. We conclude that
      high income buys life satisfaction but not happiness, and that low income is
      associated both with low life evaluation and low emotional well-being.

PMID- 20823224
TI  - Unveiling a phytoplankton hotspot at a narrow boundary between coastal and
      offshore waters.
AB  - In terrestrial ecosystems, transitional areas between different plant communities
      (ecotones) are formed by steep environmental gradients and are commonly
      characterized by high species diversity and primary productivity, which in turn
      influences the foodweb structure of these regions. Whether comparable zones of
      elevated diversity and productivity characterize ecotones in the oceans remains
      poorly understood. Here we describe a previously hidden hotspot of phytoplankton
      diversity and productivity in a narrow but seasonally persistent transition zone
      at the intersection of iron-poor, nitrate-rich offshore waters and iron-rich,
      nitrate-poor coastal waters of the Northeast Pacific Ocean. Novel continuous
      measurements of phytoplankton cell abundance and composition identified a complex
      succession of blooms of five distinct size classes of phytoplankton populations
      within a 100-km-wide transition zone. The blooms appear to be fueled by natural
      iron enrichment of offshore communities as they are transported toward the coast.
      The observed succession of phytoplankton populations is likely driven by spatial
      gradients in iron availability or time since iron enrichment. Regardless of the
      underlying mechanism, the resulting communities have a strong impact on the
      regional biogeochemistry as evidenced by the low partial pressure of CO(2) and
      the nearly complete depletion of nutrients. Enhanced phytoplankton productivity
      and diversity associated with steep environmental gradients are expected wherever
      water masses with complementary nutrient compositions mix to create a region more
      favorable for phytoplankton growth. The ability to detect and track these
      important but poorly characterized marine ecotones is critical for understanding
      their impact on productivity and ecosystem structure in the oceans.

PMID- 20823225
TI  - Potential for reduced methane and carbon dioxide emissions from livestock and
      pasture management in the tropics.
AB  - We estimate the potential reductions in methane and carbon dioxide emissions from
      several livestock and pasture management options in the mixed and rangeland-based
      production systems in the tropics. The impacts of adoption of improved pastures,
      intensifying ruminant diets, changes in land-use practices, and changing breeds
      of large ruminants on the production of methane and carbon dioxide are calculated
      for two levels of adoption: complete adoption, to estimate the upper limit to
      reductions in these greenhouse gases (GHGs), and optimistic but plausible
      adoption rates taken from the literature, where these exist. Results are
      expressed both in GHG per ton of livestock product and in Gt CO(2)-eq. We
      estimate that the maximum mitigation potential of these options in the land-based
      livestock systems in the tropics amounts to approximately 7% of the global
      agricultural mitigation potential to 2030. Using historical adoption rates from
      the literature, the plausible mitigation potential of these options could
      contribute approximately 4% of global agricultural GHG mitigation. This could be
      worth on the order of $1.3 billion per year at a price of $20 per t CO(2)-eq. The
      household-level and sociocultural impacts of some of these options warrant
      further study, however, because livestock have multiple roles in tropical systems
      that often go far beyond their productive utility.

PMID- 20823226
TI  - Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's
      ubiquitination and protective function.
AB  - Mutations in PARK2/Parkin, which encodes a ubiquitin E3 ligase, cause autosomal
      recessive Parkinson disease (PD). Here we show that the nonreceptor tyrosine
      kinase c-Abl phosphorylates tyrosine 143 of parkin, inhibiting parkin's ubiquitin
      E3 ligase activity and protective function. c-Abl is activated by dopaminergic
      stress and by dopaminergic neurotoxins, 1-methyl-4-phenylpyridinium (MPP(+)) in
      vitro and in vivo by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), leading
      to parkin inactivation, accumulation of the parkin substrates aminoacyl-tRNA
      synthetase-interacting multifunctional protein type 2 (AIMP2) (p38/JTV-1) and
      fuse-binding protein 1 (FBP1), and cell death. STI-571, a c-Abl-family kinase
      inhibitor, prevents the phosphorylation of parkin, maintaining parkin in a
      catalytically active and protective state. STI-571's protective effects require
      parkin, as shRNA knockdown of parkin prevents STI-571 protection. Conditional
      knockout of c-Abl in the nervous system also prevents the phosphorylation of
      parkin, the accumulation of its substrates, and subsequent neurotoxicity in
      response to MPTP intoxication. In human postmortem PD brain, c-Abl is active,
      parkin is tyrosine-phosphorylated, and AIMP2 and FBP1 accumulate in the
      substantia nigra and striatum. Thus, tyrosine phosphorylation of parkin by c-Abl
      is a major posttranslational modification that inhibits parkin function, possibly
      contributing to pathogenesis of sporadic PD. Moreover, inhibition of c-Abl may be
      a neuroprotective approach in the treatment of PD.

PMID- 20823227
TI  - A small molecule accelerates neuronal differentiation in the adult rat.
AB  - Adult neurogenesis occurs in mammals and provides a mechanism for continuous
      neural plasticity in the brain. However, little is known about the molecular
      mechanisms regulating hippocampal neural progenitor cells (NPCs) and whether
      their fate can be pharmacologically modulated to improve neural plasticity and
      regeneration. Here, we report the characterization of a small molecule (KHS101)
      that selectively induces a neuronal differentiation phenotype. Mechanism of
      action studies revealed a link of KHS101 to cell cycle exit and specific binding
      to the TACC3 protein, whose knockdown in NPCs recapitulates the KHS101-induced
      phenotype. Upon systemic administration, KHS101 distributed to the brain and
      resulted in a significant increase in neuronal differentiation in vivo. Our
      findings indicate that KHS101 accelerates neuronal differentiation by interaction
      with TACC3 and may provide a basis for pharmacological intervention directed at
      endogenous NPCs.

PMID- 20823228
TI  - Thymopoiesis in mice depends on a Foxn1-positive thymic epithelial cell lineage.
AB  - The thymus is essential for T-cell development. Here, we focus on the role of the
      transcription factor Foxn1 in the development and function of thymic epithelial
      cells (TECs) of the mouse. TECs are of endodermal origin; they initially express
      Foxn1 and give rise to orthotopic (thoracic) and additional (cervical) thymi.
      Using Foxn1-directed cytoablation, we show that during embryogenesis, cervical
      thymi develop a few days after the thoracic lobes, and that bipotent epithelial
      progenitors of cortical and medullary compartments express Foxn1. We also show
      that following acute selective near-total ablation during embryogenesis, complete
      regeneration of TECs does not occur, providing an animal model for human thymic
      aplasia syndromes. Finally, we address the functional role of Foxn1-negative TECs
      that arise postnatally in the mouse. Lineage tracing shows that such Foxn1
      negative TECs are descendants of Foxn1-positive progenitors; furthermore, Foxn1
      directed subacute intoxication of TECs by polyglutamine-containing EGFP proteins
      indicates that a presumptive Foxn1-independent lineage does not contribute to
      thymopoietic function of the adult thymus. Our findings therefore support the
      notion that Foxn1 is the essential transcription factor regulating the
      differentiation of TECs and that its expression marks the major functional
      lineage of TECs in embryonic and adult thymic tissue.

PMID- 20823229
TI  - Viral terminal protein directs early organization of phage DNA replication at the
      bacterial nucleoid.
AB  - The mechanism leading to protein-primed DNA replication has been studied
      extensively in vitro. However, little is known about the in vivo organization of
      the proteins involved in this fundamental process. Here we show that the terminal
      proteins (TPs) of phages phi29 and PRD1, infecting the distantly related bacteria
      Bacillus subtilis and Escherichia coli, respectively, associate with the host
      bacterial nucleoid independently of other viral-encoded proteins. Analyses of
      phage phi29 revealed that the TP N-terminal domain (residues 1-73) possesses
      sequence-independent DNA-binding capacity and is responsible for its nucleoid
      association. Importantly, we show that in the absence of the TP N-terminal domain
      the efficiency of phi29 DNA replication is severely affected. Moreover, the TP
      recruits the phage DNA polymerase to the bacterial nucleoid, and both proteins
      later are redistributed to enlarged helix-like structures in an MreB cytoskeleton
      dependent way. These data disclose a key function for the TP in vivo: organizing
      the early viral DNA replication machinery at the cell nucleoid.

PMID- 20823230
TI  - Hippocampal long-term depression is required for the consolidation of spatial
      memory.
AB  - Although NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) and long
      term depression (LTD) of glutamatergic transmission are candidate mechanisms for
      long-term spatial memory, the precise contributions of LTP and LTD remain poorly
      understood. Here, we report that LTP and LTD in the hippocampal CA1 region of
      freely moving adult rats were prevented by NMDAR 2A (GluN2A) and 2B subunit
      (GluN2B) preferential antagonists, respectively. These results strongly suggest
      that NMDAR subtype preferential antagonists are appropriate tools to probe the
      roles of LTP and LTD in spatial memory. Using a Morris water maze task, the LTP
      blocking GluN2A antagonist had no significant effect on any aspect of
      performance, whereas the LTD-blocking GluN2B antagonist impaired spatial memory
      consolidation. Moreover, similar spatial memory deficits were induced by
      inhibiting the expression of LTD with intrahippocampal infusion of a short
      peptide that specifically interferes with AMPA receptor endocytosis. Taken
      together, our findings support a functional requirement of hippocampal CA1 LTD in
      the consolidation of long-term spatial memory.

PMID- 20823231
TI  - Essential role of c-myb in definitive hematopoiesis is evolutionarily conserved.
AB  - The transcription factor c-myb has emerged as one of the key regulators of
      vertebrate hematopoiesis. In mice, it is dispensable for primitive stages of
      blood cell development but essentially required for definitive hematopoiesis.
      Using a conditional knock-out strategy, recent studies have indicated that c-myb
      is required for self-renewal of mouse hematopoietic stem cells. Here, we describe
      and characterize the c-myb mutant in a lower vertebrate, the zebrafish Danio
      rerio. The recessive loss-of-function allele of c-myb (c-myb(t25127)) was
      identified in a collection of N-ethyl-N-nitrosourea (ENU)-induced mutants
      exhibiting a failure of thymopoiesis. The sequence of the mutant allele predicts
      a missense mutation (I181N) in the middle of the DNA recognition helix of repeat
      3 of the highly conserved DNA binding domain. In keeping with the findings in the
      mouse, primitive hematopoiesis is not affected in the c-myb mutant fish. By
      contrast, definitive hematopoiesis fails, resulting in the loss of all blood
      cells by day 20 of development. Thus, the mutant fish lack lymphocytes and other
      white and red blood cells; nonetheless, they survive for 2-3 mo but show stunted
      growth. Because the mutant fish survive into early adulthood, it was possible to
      directly show that their definitive hematopoiesis is permanently extinguished.
      Our results, therefore, suggest that the key role of c-myb in definitive
      hematopoiesis is similar to that in mammals and must have become established
      early in vertebrate evolution.

PMID- 20823232
TI  - In vivo pair correlation analysis of EGFP intranuclear diffusion reveals DNA
      dependent molecular flow.
AB  - No methods proposed thus far have the capability to measure overall molecular
      flow in the nucleus of living cells. Here, we apply the pair correlation function
      analysis (pCF) to measure molecular anisotropic diffusion in the interphase
      nucleus of live cells. In the pCF method, we cross-correlate fluctuations at
      several distances and locations within the nucleus, enabling us to define
      migration paths and barriers to diffusion. We use monomeric EGFP as a
      prototypical inert molecule and measure flow in and between different nuclear
      environments. Our results suggest that there are two disconnect molecular flows
      throughout the nucleus associated with high and low DNA density regions. We show
      that different density regions of DNA form a networked channel that allows EGFP
      to diffuse freely throughout, however with restricted ability to traverse the
      channel. We also observe rare and sudden bursts of molecules traveling across DNA
      density regions with characteristic time of ~300 ms, suggesting intrinsic
      localized change in chromatin structure. This is a unique in vivo demonstration
      of the intricate chromatin network showing channel directed diffusion of an inert
      molecule with high spatial and temporal resolution.

PMID- 20823233
TI  - High-resolution forest carbon stocks and emissions in the Amazon.
AB  - Efforts to mitigate climate change through the Reduced Emissions from
      Deforestation and Degradation (REDD) depend on mapping and monitoring of tropical
      forest carbon stocks and emissions over large geographic areas. With a new
      integrated use of satellite imaging, airborne light detection and ranging, and
      field plots, we mapped aboveground carbon stocks and emissions at 0.1-ha
      resolution over 4.3 million ha of the Peruvian Amazon, an area twice that of all
      forests in Costa Rica, to reveal the determinants of forest carbon density and to
      demonstrate the feasibility of mapping carbon emissions for REDD. We discovered
      previously unknown variation in carbon storage at multiple scales based on
      geologic substrate and forest type. From 1999 to 2009, emissions from land use
      totaled 1.1% of the standing carbon throughout the region. Forest degradation,
      such as from selective logging, increased regional carbon emissions by 47% over
      deforestation alone, and secondary regrowth provided an 18% offset against total
      gross emissions. Very high-resolution monitoring reduces uncertainty in carbon
      emissions for REDD programs while uncovering fundamental environmental controls
      on forest carbon storage and their interactions with land-use change.

PMID- 20823234
TI  - Notch signaling contributes to proliferation and tumor formation of human T-cell
      leukemia virus type 1-associated adult T-cell leukemia.
AB  - The Notch signaling pathway plays an important role in cellular proliferation,
      differentiation, and apoptosis. Unregulated activation of Notch signaling can
      result in excessive cellular proliferation and cancer. Human T-cell leukemia
      virus type 1 (HTLV-I) is the etiological agent of adult T-cell leukemia (ATL).
      The disease has a dismal prognosis and is invariably fatal. In this study, we
      report a high frequency of constitutively activated Notch in ATL patients. We
      found activating mutations in Notch in more than 30% of ATL patients. These
      activating mutations are phenotypically different from those previously reported
      in T-ALL leukemias and may represent polymorphisms for activated Notch in human
      cancers. Compared with the exclusive activating frameshift mutations in the
      proline, glutamic acid, serine, and threonine (PEST) domain in T-ALLs, those in
      ATLs have, in addition, single-substitution mutations in this domain leading to
      reduced CDC4/Fbw7-mediated degradation and stabilization of the intracellular
      cleaved form of Notch1 (ICN1). Finally, we demonstrated that inhibition of Notch
      signaling by gamma-secretase inhibitors reduced tumor cell proliferation and
      tumor formation in ATL-engrafted mice. These data suggest that activated Notch
      may be important to ATL pathogenesis and reveal Notch1 as a target for
      therapeutic intervention in ATL patients.

PMID- 20823235
TI  - Corepressor for element-1-silencing transcription factor preferentially mediates
      gene networks underlying neural stem cell fate decisions.
AB  - The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive
      silencer factor (REST/NRSF) silences neuronal genes in neural stem cells (NSCs)
      and nonneuronal cells through its role as a dynamic modular platform for
      recruitment of transcriptional and epigenetic regulatory cofactors to RE1
      containing promoters. In embryonic stem cells, the REST regulatory network is
      highly integrated with the transcriptional circuitry governing self-renewal and
      pluripotency, although its exact functional role is unclear. The C-terminal
      cofactor for REST, CoREST, also acts as a modular scaffold, but its cell type
      specific roles have not been elucidated. We used chromatin immunoprecipitation-on
      chip to examine CoREST and REST binding sites in NSCs and their proximate
      progenitor species. In NSCs, we identified a larger number of CoREST (1,820)
      compared with REST (322) target genes. The majority of these CoREST targets do
      not contain known RE1 motifs. Notably, these CoREST target genes do play
      important roles in pluripotency networks, in modulating NSC identity and fate
      decisions and in epigenetic processes previously associated with both REST and
      CoREST. Moreover, we found that NSC-mediated developmental transitions were
      associated primarily with liberation of CoREST from promoters with
      transcriptional repression favored in less lineage-restricted radial glia and
      transcriptional activation favored in more lineage-restricted neuronal
      oligodendrocyte precursors. Clonal NSC REST and CoREST gene manipulation
      paradigms further revealed that CoREST has largely independent and previously
      uncharacterized roles in promoting NSC multilineage potential and modulating
      early neural fate decisions.

PMID- 20823236
TI  - PCNA and MutLalpha: partners in crime in triplet repeat expansion?

PMID- 20823237
TI  - Scaling expectations for the time to establishment of complex adaptations.
AB  - Although the vast majority of research in evolutionary biology is focused on
      adaption, a general theory for the population-genetic mechanisms by which complex
      adaptations are acquired remains to be developed. The issue explored here is the
      procurement of novel traits that specifically require multiple mutations to
      achieve a fitness advantage. By highlighting the roles played by the forces of
      mutation, recombination, and random genetic drift, and drawing from observations
      on the joint constraints on these factors, the ways in which rates of acquisition
      of specific types of adaptations scale with population size are explored. These
      general results provide insight into a number of ongoing controversies regarding
      the molecular basis of adaptation, including the adaptive utility of
      recombination and the role of drift in the passage through adaptive valleys.

PMID- 20823238
TI  - Constitutively active androgen receptor splice variants expressed in castration
      resistant prostate cancer require full-length androgen receptor.
AB  - Androgen receptor (AR) splice variants lacking the ligand binding domain (ARVs),
      originally isolated from prostate cancer cell lines derived from a single
      patient, are detected in normal and malignant human prostate tissue, with the
      highest levels observed in late stage, castration-resistant prostate cancer. The
      most studied variant (called AR-V7 or AR3) activates AR reporter genes in the
      absence of ligand and therefore, could play a role in castration resistance. To
      explore the range of potential ARVs, we screened additional human and murine
      prostate cancer models using conventional and next generation sequencing
      technologies and detected several structurally diverse AR isoforms. Some, like AR
      V7/AR3, display gain of function, whereas others have dominant interfering
      activity. We also find that ARV expression increases acutely in response to
      androgen withdrawal, is suppressed by testosterone, and in some models, is
      coupled to full-length AR (AR-FL) mRNA production. As expected, constitutively
      active, ligand-independent ARVs such as AR-V7/AR3 are sufficient to confer
      anchorage-independent (in vitro) and castration-resistant (in vivo) growth.
      Surprisingly, this growth is blocked by ligand binding domain-targeted
      antiandrogens, such as MDV3100, or by selective siRNA silencing of AR-FL,
      indicating that the growth-promoting effects of ARVs are mediated through AR-FL.
      These data indicate that the increase in ARV expression in castrate-resistant
      prostate cancer is an acute response to castration rather than clonal expansion
      of castration or antiandrogen-resistant cells expressing gain of function ARVs,
      and furthermore, they provide a strategy to overcome ARV function in the clinic.

PMID- 20823239
TI  - Human mucosal in vivo transcriptome responses to three lactobacilli indicate how
      probiotics may modulate human cellular pathways.
AB  - Probiotic bacteria, specific representatives of bacterial species that are a
      common part of the human microbiota, are proposed to deliver health benefits to
      the consumer by modulation of intestinal function through largely unknown
      molecular mechanisms. To explore in vivo mucosal responses of healthy adults to
      probiotics, we obtained transcriptomes in an intervention study after a double
      blind placebo-controlled cross-over design. In the mucosa of the proximal small
      intestine of healthy volunteers, probiotic strains from the species Lactobacillus
      acidophilus, L. casei, and L. rhamnosus each induced differential gene-regulatory
      networks and pathways in the human mucosa. Comprehensive analyses revealed that
      these transcriptional networks regulate major basal mucosal processes and
      uncovered remarkable similarity to response profiles obtained for specific
      bioactive molecules and drugs. This study elucidates how intestinal mucosa of
      healthy humans perceives different probiotics and provides avenues for rationally
      designed tests of clinical applications.

PMID- 20823241
TI  - Climate not to blame for African civil wars.
AB  - Vocal actors within policy and practice contend that environmental variability
      and shocks, such as drought and prolonged heat waves, drive civil wars in Africa.
      Recently, a widely publicized scientific article appears to substantiate this
      claim. This paper investigates the empirical foundation for the claimed
      relationship in detail. Using a host of different model specifications and
      alternative measures of drought, heat, and civil war, the paper concludes that
      climate variability is a poor predictor of armed conflict. Instead, African civil
      wars can be explained by generic structural and contextual conditions: prevalent
      ethno-political exclusion, poor national economy, and the collapse of the Cold
      War system.

PMID- 20823240
TI  - Selective viral vector transduction of ErbB4 expressing cortical interneurons in
      vivo with a viral receptor-ligand bridge protein.
AB  - Both treatment of disease and basic studies of complex tissues can benefit from
      directing viral vector infection to specific cell types. We have used a unique
      cell targeting method to direct viral vector transduction to cerebral cortical
      neurons expressing the neuregulin (NRG) receptor ErbB4; both NRG and ErbB4 have
      been implicated in schizophrenia, and ErbB4 expression in cerebral cortex is
      known to be restricted to inhibitory neurons. We find that a bridge protein
      composed of the avian viral receptor TVB fused to NRG, along with EnvB
      pseudotyped virus, is able to direct infection selectively to ErbB4-expressing
      inhibitory cortical neurons in vivo. Interestingly, although ErbB4 is expressed
      in a broad range of cortical inhibitory cell types, NRG-dependent infection is
      restricted to a more selective subset of inhibitory cell types. These results
      demonstrate a tool that can be used for further studies of NRG and ErbB receptors
      in brain circuits and demonstrate the feasibility for further development of
      related bridge proteins to target gene expression to other specific cell types in
      complex tissues.

PMID- 20823242
TI  - A sensitive period for environmental regulation of eating behavior and leptin
      sensitivity.
AB  - Western lifestyle contributes to body weight dysregulation. Leptin down-regulates
      food intake by modulating the activity of neural circuits in the hypothalamic
      arcuate nucleus (ARC), and resistance to this hormone constitutes a permissive
      condition for obesity. Physical exercise modulates leptin sensitivity in diet
      induced obese rats. The role of other lifestyle components in modulating leptin
      sensitivity remains elusive. Environmentally enriched mice were used to explore
      the effects of lifestyle change on leptin production/action and other metabolic
      parameters. We analyzed adult mice exposed to environmental enrichment (EE),
      which showed decreased leptin, reduced adipose mass, and increased food intake.
      We also analyzed 50-d-old mice exposed to either EE (YEE) or physical exercise
      (YW) since birth, both of which showed decreased leptin. YEE mice showed no
      change in food intake, increased response to leptin administration, increased
      activation of STAT3 in the ARC. The YW leptin-induced food intake response was
      intermediate between young mice kept in standard conditions and YEE. YEE
      exhibited increased and decreased ratios of excitatory/inhibitory synapses onto
      alpha-melanocyte-stimulating hormone and agouti-related peptide neurons of the
      ARC, respectively. We also analyzed animals as described for YEE and then placed
      in standard cages for 1 mo. They showed no altered leptin production/action but
      demonstrated changes in excitatory/inhibitory synaptic contacts in the ARC
      similar to YEE. EE and physical activity resulted in improved insulin
      sensitivity. In conclusion, EE and physical activity had an impact on feeding
      behavior, leptin production/action, and insulin sensitivity, and EE affected ARC
      circuitry. The leptin-hypothalamic axis is maximally enhanced if environmental
      stimulation is applied during development.

PMID- 20823243
TI  - Long-term reductions in anthropogenic nutrients link to improvements in
      Chesapeake Bay habitat.
AB  - Great effort continues to focus on ecosystem restoration and reduction of
      nutrient inputs thought to be responsible, in part, for declines in estuary
      habitats worldwide. The ability of environmental policy to address restoration is
      limited, in part, by uncertainty in the relationships between costly restoration
      and benefits. Here, we present results from an 18-y field investigation (1990
      2007) of submerged aquatic vegetation (SAV) community dynamics and water quality
      in the Potomac River, a major tributary of the Chesapeake Bay. River and
      anthropogenic discharges lower water clarity by introducing nutrients that
      stimulate phytoplankton and epiphyte growth as well as suspended sediments.
      Efforts to restore the Chesapeake Bay are often viewed as failing. Overall
      nutrient reduction and SAV restoration goals have not been met. In the Potomac
      River, however, reduced in situ nutrients, wastewater-treatment effluent
      nitrogen, and total suspended solids were significantly correlated to increased
      SAV abundance and diversity. Species composition and relative abundance also
      correlated with nutrient and water-quality conditions, indicating declining
      fitness of exotic species relative to native species during restoration. Our
      results suggest that environmental policies that reduce anthropogenic nutrient
      inputs do result in improved habitat quality, with increased diversity and native
      species abundances. The results also help elucidate why SAV cover has improved
      only in some areas of the Chesapeake Bay.

PMID- 20823244
TI  - LIL3, a light-harvesting-like protein, plays an essential role in chlorophyll and
      tocopherol biosynthesis.
AB  - The light-harvesting chlorophyll-binding (LHC) proteins are major constituents of
      eukaryotic photosynthetic machinery. In plants, six different groups of proteins,
      LHC-like proteins, share a conserved motif with LHC. Although the evolution of
      LHC and LHC-like proteins is proposed to be a key for the diversification of
      modern photosynthetic eukaryotes, our knowledge of the evolution and functions of
      LHC-like proteins is still limited. In this study, we aimed to understand
      specifically the function of one type of LHC-like proteins, LIL3 proteins, by
      analyzing Arabidopsis mutants lacking them. The Arabidopsis genome contains two
      gene copies for LIL3, LIL3:1 and LIL3:2. In the lil3:1/lil3:2 double mutant, the
      majority of chlorophyll molecules are conjugated with an unsaturated
      geranylgeraniol side chain. This mutant is also deficient in alpha-tocopherol.
      These results indicate that reduction of both the geranylgeraniol side chain of
      chlorophyll and geranylgeranyl pyrophosphate, which is also an essential
      intermediate of tocopherol biosynthesis, is compromised in the lil3 mutants. We
      found that the content of geranylgeranyl reductase responsible for these
      reactions was severely reduced in the lil3 double mutant, whereas the mRNA level
      for this enzyme was not significantly changed. We demonstrated an interaction of
      geranylgeranyl reductase with both LIL3 isoforms by using a split ubiquitin
      assay, bimolecular fluorescence complementation, and combined blue-native and SDS
      polyacrylamide gel electrophoresis. We propose that LIL3 is functionally involved
      in chlorophyll and tocopherol biosynthesis by stabilizing geranylgeranyl
      reductase.

PMID- 20823245
TI  - Fatal attraction: bacterial bait lures worms to their death.

PMID- 20823246
TI  - Oral methylphenidate normalizes cingulate activity in cocaine addiction during a
      salient cognitive task.
AB  - Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a
      hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical
      function, enhancing task salience and improving associated cognitive abilities,
      in other frontal lobe pathologies; however, in clinical trials, MPH did not
      improve treatment outcome in cocaine addiction. We hypothesized that oral MPH
      will attenuate ACC hypoactivations and improve associated performance during a
      salient cognitive task in individuals with cocaine-use disorders (CUD). In the
      current functional MRI study, we used a rewarded drug cue-reactivity task
      previously shown to be associated with hypoactivations in both major ACC
      subdivisions (implicated in default brain function) in CUD compared with healthy
      controls. The task was performed by 13 CUD and 14 matched healthy controls on 2
      d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a
      counterbalanced fashion. Results show that oral MPH increased responses to this
      salient cognitive task in both major ACC subdivisions (including the caudal
      dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal
      cortex) in the CUD. These functional MRI results were associated with reduced
      errors of commission (a common impulsivity measure) and improved task accuracy,
      especially during the drug (vs. neutral) cue-reactivity condition in all
      subjects. The clinical application of such MPH-induced brain-behavior
      enhancements remains to be tested.

PMID- 20823247
TI  - Differential effects of STAT5 and PI3K/AKT signaling on effector and memory CD8 T
      cell survival.
AB  - During viral infection, effector CD8 T cells contract to form a population of
      protective memory cells that is maintained by IL-7 and IL-15. The mechanisms that
      control effector cell death during infection are poorly understood. We
      investigated how short- and long-lived antiviral CD8 T cells differentially used
      the survival and cell growth pathways PI3K/AKT and JAK/STAT5. In response to IL
      15, long-lived memory precursor cells activated AKT significantly better than
      short-lived effector cells. However, constitutive AKT activation did not enhance
      memory CD8 T-cell survival but rather repressed IL-7 and IL-15 receptor
      expression, STAT5 phosphorylation, and BCL2 expression. Conversely, constitutive
      STAT5 activation profoundly enhanced effector and memory CD8 T-cell survival and
      augmented homeostatic proliferation, AKT activation, and BCL2 expression. Taken
      together, these data illustrate that effector and memory cell viability depends
      on properly balanced PI3K/AKT signaling and the maintenance of STAT5 signaling.

PMID- 20823248
TI  - Dual stage synthesis and crucial role of cytoadherence-linked asexual gene 9 in
      the surface expression of malaria parasite var proteins.
AB  - Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family members
      mediate the adherence of parasite-infected red blood cells (IRBCs) to various
      host receptors. A previous study has shown that the parasite protein,
      cytoadherence-linked asexual gene 9 (CLAG9), is also essential for IRBC
      adherence. However, how CLAG9 influences this process remains unknown. In this
      study, we show that CLAG9 interacts with VAR2CSA, a PfEMP1 that mediates IRBC
      adherence to chondroitin 4-sulfate in the placenta. Importantly, our results show
      that the adherent parasites synthesize CLAG9 at two stages--the early ring and
      late trophozoite stages. Localization studies revealed that a substantial level
      of CLAG9 is located mainly at or in close proximity of the IRBC membrane in
      association with VAR2CSA. Upon treatment of IRBCs with trypsin, a significant
      amount of CLAG9 (~150 kDa) was converted into ~142-kDa polypeptide. Together
      these data demonstrate that a considerable amount of CLAG9 is embedded in the
      IRBC membrane such that at least a portion of the polypeptide at either N or C
      terminus is exposed on the cell surface. In parasites lacking CLAG9, VAR2CSA
      failed to express on the IRBC surface and was located within the parasite. Based
      on these findings, we propose that CLAG9 plays a critical role in the trafficking
      of PfEMP1s onto the IRBC surface. These results have important implications for
      the development of therapeutics for cerebral, placental, and other cytoadherence
      associated malaria illnesses.

PMID- 20823249
TI  - Mutations in mouse Aspm (abnormal spindle-like microcephaly associated) cause not
      only microcephaly but also major defects in the germline.
AB  - Mutations in ASPM (abnormal spindle-like microcephaly associated) cause primary
      microcephaly in humans, a disorder characterized by a major reduction in brain
      size in the apparent absence of nonneurological anomalies. The function of the
      Aspm protein in neural progenitor cell expansion, as well as its localization to
      the mitotic spindle and midbody, suggest that it regulates brain development by a
      cell division-related mechanism. Furthermore, evidence that positive selection
      affected ASPM during primate evolution has led to suggestions that such a
      function changed during primate evolution. Here, we report that in Aspm mutant
      mice, truncated Aspm proteins similar to those causing microcephaly in humans
      fail to localize to the midbody during M-phase and cause mild microcephaly. A
      human ASPM transgene rescues this phenotype but, interestingly, does not cause a
      gain of function. Strikingly, truncated Aspm proteins also cause a massive loss
      of germ cells, resulting in a severe reduction in testis and ovary size
      accompanied by reduced fertility. These germline effects, too, are fully rescued
      by the human ASPM transgene, indicating that ASPM is functionally similar in mice
      and humans. Our findings broaden the spectrum of phenotypic effects of ASPM
      mutations and raise the possibility that positive selection of ASPM during
      primate evolution reflects its function in the germline.

PMID- 20823250
TI  - Dimensionality of mate choice, sexual isolation, and speciation.
AB  - Multiple cues, across multiple sensory modalities, are involved in mate choice in
      a wide range of animal taxa. This multiplicity leads to the prediction that, in
      adaptive radiations, sexual isolation results from divergence in multiple
      dimensions. However, difficulties in directly measuring preferences and detecting
      multiple effects limit our ability to empirically assess the number of
      independent traits contributing to mate choice and sexual isolation. We present
      an approach to estimate the dimensionality of sexual isolation using mating
      trials across groups of related populations. We analyze nine radiations: seven in
      fruit flies (Drosophila) and one each in salamanders (Desmognathus) and cichlid
      fishes (Pseudotropheus). We find strong evidence that multiple latent traits-
      linear combinations of phenotypic traits and preferences--are responsible for the
      patterns of sexual isolation in all nine radiations but that dimensionality has a
      strong upper limit. Just two latent traits are implicated in the majority of
      cases. Mapping along latent trait axes tests predictions of sexual-selection
      models and allows correlation with specific phenotypic traits and functional
      components of mate choice. We find support for the role of stabilizing natural
      selection on the sexually selected (male) traits. In the cichlids, latent-trait
      axes incorporate male-coloration patterns and exhibit convergence as well as
      divergence among populations. In the salamanders, temporal patterning in sensory
      modalities and male vs. female preferences are reflected in different latent
      trait axes.

PMID- 20823251
TI  - Deficiency of 5-hydroxyisourate hydrolase causes hepatomegaly and hepatocellular
      carcinoma in mice.
AB  - With the notable exception of humans, uric acid is degraded to (S)-allantoin in a
      biochemical pathway catalyzed by urate oxidase, 5-hydroxyisourate (HIU)
      hydrolase, and 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase in
      most vertebrate species. A point mutation in the gene encoding mouse HIU
      hydrolase, Urah, that perturbed uric acid metabolism within the liver was
      discovered during a mutagenesis screen in mice. The predicted substitution of
      cysteine for tyrosine in a conserved helical region of the mutant-encoded HIU
      hydrolase resulted in undetectable protein expression. Mice homozygous for this
      mutation developed elevated platelet counts secondary to excess thrombopoietin
      production and hepatomegaly. The majority of homozygous mutant mice also
      developed hepatocellular carcinoma, and tumor development was accelerated by
      exposure to radiation. The development of hepatomegaly and liver tumors in mice
      lacking Urah suggests that uric acid metabolites may be toxic and that urate
      oxidase activity without HIU hydrolase function may affect liver growth and
      transformation. The absence of HIU hydrolase in humans predicts slowed metabolism
      of HIU after clinical administration of exogenous urate oxidase in conditions of
      uric acid-related pathology. The data suggest that prolonged urate oxidase
      therapy should be combined with careful assessment of toxicity associated with
      extrahepatic production of uric acid metabolites.

PMID- 20823252
TI  - Brain size, life history, and metabolism at the marsupial/placental dichotomy.
AB  - The evolution of mammalian brain size is directly linked with the evolution of
      the brain's unique structure and performance. Both maternal life history
      investment traits and basal metabolic rate (BMR) correlate with relative brain
      size, but current hypotheses regarding the details of these relationships are
      based largely on placental mammals. Using encephalization quotients, partial
      correlation analyses, and bivariate regressions relating brain size to maternal
      investment times and BMR, we provide a direct quantitative comparison of brain
      size evolution in marsupials and placentals, whose reproduction and metabolism
      differ extensively. Our results show that the misconception that marsupials are
      systematically smaller-brained than placentals is driven by the inclusion of one
      large-brained placental clade, Primates. Marsupial and placental brain size
      partial correlations differ in that marsupials lack a partial correlation of BMR
      with brain size. This contradicts hypotheses stating that the maintenance of
      relatively larger brains requires higher BMRs. We suggest that a positive BMR
      brain size correlation is a placental trait related to the intimate physiological
      contact between mother and offspring during gestation. Marsupials instead achieve
      brain sizes comparable to placentals through extended lactation. Comparison with
      avian brain evolution suggests that placental brain size should be constrained
      due to placentals' relative precociality, as has been hypothesized for precocial
      bird hatchlings. We propose that placentals circumvent this constraint because of
      their focus on gestation, as opposed to the marsupial emphasis on lactation.
      Marsupials represent a less constrained condition, demonstrating that hypotheses
      regarding placental brain size evolution cannot be generalized to all mammals.

PMID- 20823253
TI  - Gene limiting cadmium accumulation in rice.
AB  - Intake of toxic cadmium (Cd) from rice caused Itai-itai disease in the past and
      it is still a threat for human health. Therefore, control of the accumulation of
      Cd from soil is an important food-safety issue, but the molecular mechanism for
      the control is unknown. Herein, we report a gene (OsHMA3) responsible for low Cd
      accumulation in rice that was isolated from a mapping population derived from a
      cross between a high and low Cd-accumulating cultivar. The gene encodes a
      transporter belonging to the P(1B)-type ATPase family, but shares low similarity
      with other members. Heterologous expression in yeast showed that the transporter
      from the low-Cd cultivar is functional, but the transporter from the high-Cd
      cultivar had lost its function, probably because of the single amino acid
      mutation. The transporter is mainly expressed in the tonoplast of root cells at a
      similar level in both the low and high Cd-accumulating cultivars. Overexpression
      of the functional gene from the low Cd-accumulating cultivar selectively
      decreased accumulation of Cd, but not other micronutrients in the grain. Our
      results indicated that OsHMA3 from the low Cd-accumulating cultivar limits
      translocation of Cd from the roots to the above-ground tissues by selectively
      sequestrating Cd into the root vacuoles.

PMID- 20823254
TI  - Photophoretic levitation of engineered aerosols for geoengineering.
AB  - Aerosols could be injected into the upper atmosphere to engineer the climate by
      scattering incident sunlight so as to produce a cooling tendency that may
      mitigate the risks posed by the accumulation of greenhouse gases. Analysis of
      climate engineering has focused on sulfate aerosols. Here I examine the
      possibility that engineered nanoparticles could exploit photophoretic forces,
      enabling more control over particle distribution and lifetime than is possible
      with sulfates, perhaps allowing climate engineering to be accomplished with fewer
      side effects. The use of electrostatic or magnetic materials enables a class of
      photophoretic forces not found in nature. Photophoretic levitation could loft
      particles above the stratosphere, reducing their capacity to interfere with ozone
      chemistry; and, by increasing particle lifetimes, it would reduce the need for
      continual replenishment of the aerosol. Moreover, particles might be engineered
      to drift poleward enabling albedo modification to be tailored to counter polar
      warming while minimizing the impact on equatorial climates.

PMID- 20823255
TI  - Self-catalyzed growth of S layers via an amorphous-to-crystalline transition
      limited by folding kinetics.
AB  - The importance of nonclassical, multistage crystallization pathways is
      increasingly evident from theoretical studies on colloidal systems and
      experimental investigations of proteins and biomineral phases. Although
      theoretical predictions suggest that proteins follow these pathways as a result
      of fluctuations that create unstable dense-liquid states, microscopic studies
      indicate these states are long-lived. Using in situ atomic force microscopy to
      follow 2D assembly of S-layer proteins on supported lipid bilayers, we have
      obtained a molecular-scale picture of multistage protein crystallization that
      reveals the importance of conformational transformations in directing the pathway
      of assembly. We find that monomers with an extended conformation first form a
      mobile adsorbed phase, from which they condense into amorphous clusters. These
      clusters undergo a phase transition through S-layer folding into crystalline
      clusters composed of compact tetramers. Growth then proceeds by formation of new
      tetramers exclusively at cluster edges, implying tetramer formation is
      autocatalytic. Analysis of the growth kinetics leads to a quantitative model in
      which tetramer creation is rate limiting. However, the estimated barrier is much
      smaller than expected for folding of isolated S-layer proteins, suggesting an
      energetic rationale for this multistage pathway.

PMID- 20823256
TI  - Computational model for nanocarrier binding to endothelium validated using in
      vivo, in vitro, and atomic force microscopy experiments.
AB  - A computational methodology based on Metropolis Monte Carlo (MC) and the weighted
      histogram analysis method (WHAM) has been developed to calculate the absolute
      binding free energy between functionalized nanocarriers (NC) and endothelial cell
      (EC) surfaces. The calculated NC binding free energy landscapes yield binding
      affinities that agree quantitatively when directly compared against analogous
      measurements of specific antibody-coated NCs (100 nm in diameter) to
      intracellular adhesion molecule-1 (ICAM-1) expressing EC surface in in vitro cell
      culture experiments. The effect of antibody surface coverage (sigma(s)) of NC on
      binding simulations reveals a threshold sigma(s) value below which the NC binding
      affinities reduce drastically and drop lower than that of single anti-ICAM-1
      molecule to ICAM-1. The model suggests that the dominant effect of changing
      sigma(s) around the threshold is through a change in multivalent interactions;
      however, the loss in translational and rotational entropies are also important.
      Consideration of shear flow and glycocalyx does not alter the computed threshold
      of antibody surface coverage. The computed trend describing the effect of
      sigma(s) on NC binding agrees remarkably well with experimental results of in
      vivo targeting of the anti-ICAM-1 coated NCs to pulmonary endothelium in mice.
      Model results are further validated through close agreement between computed NC
      rupture-force distribution and measured values in atomic force microscopy (AFM)
      experiments. The three-way quantitative agreement with AFM, in vitro (cell
      culture), and in vivo experiments establishes the mechanical, thermodynamic, and
      physiological consistency of our model. Hence, our computational protocol
      represents a quantitative and predictive approach for model-driven design and
      optimization of functionalized nanocarriers in targeted vascular drug delivery.

PMID- 20823257
TI  - Real-time single-cell response to stiffness.
AB  - Living cells adapt to the stiffness of their environment. However, cell response
      to stiffness is mainly thought to be initiated by the deformation of adhesion
      complexes under applied force. In order to determine whether cell response was
      triggered by stiffness or force, we have developed a unique method allowing us to
      tune, in real time, the effective stiffness experienced by a single living cell
      in a uniaxial traction geometry. In these conditions, the rate of traction force
      buildup dF/dt was adapted to stiffness in less than 0.1 s. This integrated fast
      response was unambiguously triggered by stiffness, and not by force. It suggests
      that early cell response could be mechanical in nature. In fact, local force
      dependent signaling through adhesion complexes could be triggered and coordinated
      by the instantaneous cell-scale adaptation of dF/dt to stiffness. Remarkably, the
      effective stiffness method presented here can be implemented on any mechanical
      setup. Thus, beyond single-cell mechanosensing, this method should be useful to
      determine the role of rigidity in many fundamental phenomena such as
      morphogenesis and development.

PMID- 20823258
TI  - Statistical tests for whether a given set of independent, identically distributed
      draws comes from a specified probability density.
AB  - We discuss several tests for determining whether a given set of independent and
      identically distributed (i.i.d.) draws does not come from a specified probability
      density function. The most commonly used are Kolmogorov-Smirnov tests,
      particularly Kuiper's variant, which focus on discrepancies between the
      cumulative distribution function for the specified probability density and the
      empirical cumulative distribution function for the given set of i.i.d. draws.
      Unfortunately, variations in the probability density function often get smoothed
      over in the cumulative distribution function, making it difficult to detect
      discrepancies in regions where the probability density is small in comparison
      with its values in surrounding regions. We discuss tests without this deficiency,
      complementing the classical methods. The tests of the present paper are based on
      the plain fact that it is unlikely to draw a random number whose probability is
      small, provided that the draw is taken from the same distribution used in
      calculating the probability (thus, if we draw a random number whose probability
      is small, then we can be confident that we did not draw the number from the same
      distribution used in calculating the probability).

PMID- 20823259
TI  - Sharp rates of decay of solutions to the nonlinear fast diffusion equation via
      functional inequalities.
AB  - The goal of this paper is to state the optimal decay rate for solutions of the
      nonlinear fast diffusion equation and, in self-similar variables, the optimal
      convergence rates to Barenblatt self-similar profiles and their generalizations.
      It relies on the identification of the optimal constants in some related Hardy
      Poincare inequalities and concludes a long series of papers devoted to
      generalized entropies, functional inequalities, and rates for nonlinear diffusion
      equations.

PMID- 20823260
TI  - Selective cell death mediated by small conditional RNAs.
AB  - Cancer cells are characterized by genetic mutations that deregulate cell
      proliferation and suppress cell death. To arrest the uncontrolled replication of
      malignant cells, conventional chemotherapies systemically disrupt cell division,
      causing diverse and often severe side effects as a result of collateral damage to
      normal cells. Seeking to address this shortcoming, we pursue therapeutic
      regulation that is conditional, activating selectively in cancer cells. This
      functionality is achieved using small conditional RNAs that interact and change
      conformation to mechanically transduce between detection of a cancer mutation and
      activation of a therapeutic pathway. Here, we describe small conditional RNAs
      that undergo hybridization chain reactions (HCR) to induce cell death via an
      innate immune response if and only if a cognate mRNA cancer marker is detected
      within a cell. The sequences of the small conditional RNAs can be designed to
      accept different mRNA markers as inputs to HCR transduction, providing a
      programmable framework for selective killing of diverse cancer cells. In cultured
      human cancer cells (glioblastoma, prostate carcinoma, Ewing's sarcoma), HCR
      transduction mediates cell death with striking efficacy and selectivity, yielding
      a 20- to 100-fold reduction in population for cells containing a cognate marker,
      and no measurable reduction otherwise. Our results indicate that programmable
      mechanical transduction with small conditional RNAs represents a fundamental
      principle for exploring therapeutic conditional regulation in living cells.

PMID- 20823261
TI  - Improvement of phi29 DNA polymerase amplification performance by fusion of DNA
      binding motifs.
AB  - Bacteriophage phi29 DNA polymerase is a unique enzyme endowed with two
      distinctive properties, high processivity and faithful polymerization coupled to
      strand displacement, that have led to the development of protocols to achieve
      isothermal amplification of limiting amounts of both circular plasmids and
      genomic DNA. To enhance the amplification efficiency of phi29 DNA polymerase, we
      have constructed chimerical DNA polymerases by fusing DNA binding domains to the
      C terminus of the polymerase. The results show that the addition of Helix-hairpin
      Helix [(HhH)(2)] domains increases DNA binding of the hybrid polymerases without
      hindering their replication rate. In addition, the chimerical DNA polymerases
      display an improved and faithful multiply primed DNA amplification proficiency on
      both circular plasmids and genomic DNA and are unique phi29 DNA polymerase
      variants with enhanced amplification performance. The reported chimerical DNA
      polymerases will contribute to make phi29 DNA polymerase-based amplification
      technologies one of the most powerful tools for genomics.

PMID- 20823262
TI  - Charge-density-based analysis of the current-voltage response of
      polythiophene/fullerene photovoltaic devices.
AB  - A key challenge for organic electronics research is to develop device models that
      correctly account for the structural and energetic disorder typically present in
      such materials. In this paper we report an approach to analyze the electrical
      performance of an organic electronic device based upon charge extraction
      measurements of charge densities and transient optoelectronic measurements of
      charge carrier dynamics. This approach is applied to a poly(3-hexyl thiophene)
      (P3HT)/6,6 phenyl C61 butyric acid methyl ester (PCBM) blend photovoltaic device.
      These measurements are employed to determine the empirical rate law for
      bimolecular recombination losses, with the energetic disorder present in the
      materials being accounted for by a charge-density-dependent recombination
      coefficient. This rate law is then employed to simulate the current/voltage
      curve. This simulation assumes the only mechanism for the loss of photogenerated
      charges is bimolecular recombination and employs no fitting parameters.
      Remarkably the simulation is in good agreement with the experimental
      current/voltage data over a wide range of operating conditions of the solar cell.
      We thus demonstrate that the primary determinant of both the open-circuit voltage
      and fill factor of P3HT:PCBM devices is bimolecular recombination. We go on to
      discuss the applicability of this analysis approach to other materials systems,
      and particularly to emphasize the effectiveness of this approach where the
      presence of disorder complicates the implementation of more conventional, voltage
      based analyses such as the Shockley diode equation.

PMID- 20823263
TI  - Breakdown of the first hyperpolarizability/bond-length alternation parameter
      relationship.
AB  - We have investigated the dependence of the static first hyperpolarizability on
      the bond-length alternation (BLA) parameter. Our analysis indicates that the
      validity of the first hyperpolarizability/BLA parameter relationship is
      restricted to the no-field, vacuum, limit, while it successively breaks down
      along with increasing polarity of a surrounding medium, becoming invalid, for
      instance, in an aqueous solution. This contention is based on a series of TD-DFT,
      TD-DFT/PCM and hybrid TD-DFT/MM calculations of the first hyperpolarizability for
      a set of molecular configurations generated from Car-Parrinello hybrid QM/MM
      simulations of the stilbazolium merocyanine chromophore in chloroform and water
      solvents, and on a rationalization by means of the two-state model for the first
      hyperpolarizability. The BLA dependence of the three parameters entering the two
      state model is shown to be qualitatively different in vacuum and in solvents.
      Particularly, in the vacuum case, the difference between ground and excited state
      dipole moments goes to zero for a vanishing BLA, which is not true in the
      presence of an aqueous medium. In the aqueous medium, an opposing behavior of the
      parameters involved in the two-state model results in an almost constant first
      hyperpolarizability with varying BLA parameter.

PMID- 20823264
TI  - The AhR is constitutively activated and affects granulosa cell features in the
      human cell line KGN.
AB  - A well-balanced activity of the aryl hydrocarbon receptor (AhR) is necessary for
      normal ovarian function. As known from murine AhR knock-out (KO) models, the AhR
      is involved in folliculogenesis, gonadotrophin receptor expression, proliferation
      of granulosa cells and intraovarian estrogen signalling. Highly potent, non
      physiological ligands such as the dioxin 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) lead to a blockade of ovulation, estrogen receptor degradation and
      reduction of estrogen levels. Estrogen synthesis is a typical function of
      granulosa cells and essential for normal cyclicity and fertility. We employed the
      human granulosa cell line KGN to further characterize AhR signalling and AhR
      function in granulosa cell physiology. Real-time PCR quantification of the target
      genes Cyp1a1 and Cyp1b1 and reporter gene assays after stimulation with TCDD or
      beta-naphthoflavone (BNF) or inhibition with alpha-naphthoflavone (ANF) or 3'
      methoxy-4'-nitroflavone (3,4-MNF) of the AhR demonstrated constitutive activity
      and functionality of AhR pathway in KGN granulosa cells. In untreated KGN cells,
      AhR protein was exclusively detected in the nuclear fraction. TCDD stimulation
      affected the gonadotrophin receptor but not estrogen receptor beta (ERbeta)
      protein expression. Additionally, the constitutively activated AhR suppressed
      aromatase expression and estrogen synthesis (enzyme-linked immunoassay, ELISA)
      and enhanced proliferation [Bromodeoxyuridine (BrdU) ELISA] of KGN cells.
      Activation of the AhR by BNF did not override this inhibitory effect on estrogen
      synthesis or proliferation. In conclusion, the AhR pathway is constitutively
      activated and functional in human KGN granulosa cells. It is a potential target
      for endocrine disruption by exogenous ligands and subsequent dysfunction of
      granulosa cells.

PMID- 20823265
TI  - The Fowler syndrome-associated protein FLVCR2 is an importer of heme.
AB  - Mutations in FLVCR2, a cell surface protein related by homology and membrane
      topology to the heme exporter/retroviral receptor FLVCR1, have recently been
      associated with Fowler syndrome, a vascular disorder of the brain. We previously
      identified FLVCR2 to function as a receptor for FY981 feline leukemia virus
      (FeLV). However, the cellular function of FLVCR2 remains unresolved. Here, we
      report the cellular function of FLVCR2 as an importer of heme, based on the
      following observations. First, FLVCR2 binds to hemin-conjugated agarose, and
      binding is competed by free hemin. Second, mammalian cells and Xenopus laevis
      oocytes expressing FLVCR2 display enhanced heme uptake. Third, heme import is
      reduced after the expression of FLVCR2-specific small interfering RNA (siRNA) or
      after the binding of the FY981 FeLV envelope protein to the FLVCR2 receptor.
      Finally, cells overexpressing FLVCR2 are more sensitive to heme toxicity, a
      finding most likely attributable to enhanced heme uptake. Tissue expression
      analysis indicates that FLVCR2 is expressed in a broad range of human tissues,
      including liver, placenta, brain, and kidney. The identification of a cellular
      function for FLVCR2 will have important implications in elucidating the
      pathogenic mechanisms of Fowler syndrome and of phenotypically associated
      disorders.

PMID- 20823266
TI  - Nuclear import of cytoplasmic poly(A) binding protein restricts gene expression
      via hyperadenylation and nuclear retention of mRNA.
AB  - Poly(A) tail length is emerging as an important marker of mRNA fate, where
      deviations from the canonical length can signal degradation or nuclear retention
      of transcripts. Pathways regulating polyadenylation thus have the potential to
      broadly influence gene expression. Here we demonstrate that accumulation of
      cytoplasmic poly(A) binding protein (PABPC) in the nucleus, which can occur
      during viral infection or other forms of cellular stress, causes mRNA
      hyperadenylation and nuclear accumulation of poly(A) RNA. This inhibits gene
      expression but does not affect mRNA stability. Unexpectedly, PABPC-induced
      hyperadenylation can occur independently of mRNA 3'-end processing yet requires
      the canonical mRNA poly(A) polymerase II. We find that nuclear PABPC-induced
      hyperadenylation is triggered by multiple divergent viral factors, suggesting
      that altering the subcellular localization of PABPC may be a commonly used
      mechanism to regulate cellular gene expression in a polyadenylation-linked
      manner.

PMID- 20823267
TI  - Thrombocytopenia in mice lacking the carboxy-terminal regulatory domain of the
      Ets transcription factor Fli1.
AB  - Targeted disruption of the Fli1 gene results in embryonic lethality. To dissect
      the roles of functional domains in Fli1, we recently generated mutant Fli1 mice
      that express a truncated Fli1 protein (Fli1(DeltaCTA)) that lacks the carboxy
      terminal regulatory (CTA) domain. Heterozygous Fli1(DeltaCTA) mice are viable,
      while homozygous mice have reduced viability. Early postnatal lethality accounts
      for 30% survival of homozygotes to adulthood. The peripheral blood of these
      viable Fli1(DeltaCTA)/Fli1(DeltaCTA) homozygous mice has reduced platelet
      numbers. Platelet aggregation and activation were also impaired and bleeding
      times significantly prolonged in these mutant mice. Analysis of mRNA from total
      bone marrow and purified megakaryocytes from Fli1(DeltaCTA)/Fli1(DeltaCTA) mice
      revealed downregulation of genes associated with megakaroyctic development,
      including c-mpl, gpIIb, gpIV, gpIX, PF4, NF-E2, MafG, and Rab27B. While Fli1 and
      GATA-1 synergistically regulate the expression of multiple megakaryocytic genes,
      the level of GATA-1 present on a subset of these promoters is reduced in vivo in
      the Fli1(DeltaCTA)/Fli1(DeltaCTA) mice, providing a possible mechanism for the
      impared transcription observed. Collectively, these data showed for the first
      time a hemostatic defect associated with the loss of a specific functional domain
      of the transcription factor Fli1 and suggest previously unknown in vivo roles in
      megakaryocytic cell differentiation.

PMID- 20823269
TI  - The function of two Rho family GTPases is determined by distinct patterns of cell
      surface localization.
AB  - Rho family GTPases are critical regulators in determining and maintaining cell
      polarity. In Saccharomyces cerevisiae, Rho3 and Cdc42 play important but distinct
      roles in regulating polarized exocytosis and overall polarity. Cdc42 is highly
      polarized during bud emergence and is specifically required for exocytosis at
      this stage. In contrast, Rho3 appears to play an important role during the
      isotropic growth of larger buds. Using a novel monoclonal antibody against Rho3,
      we find that Rho3 localizes to the cell surface in a dispersed pattern which is
      clearly distinct from that of Cdc42. Using chimeric forms of these GTPases, we
      demonstrate that a small region at the N terminus is necessary and sufficient to
      confer Rho3 localization and function onto Cdc42. Analysis of this domain reveals
      two essential elements responsible for distinguishing function. First,
      palmitoylation of a cysteine residue by the Akr1 palmitoyltransferase is required
      both for the switch of function and the switch of localization properties of this
      domain. Second, two basic residues distal to the palmitoylation site are required
      for regulating binding affinity with the Exo70 and Sec3 effectors. This
      demonstrates the importance of localization and effector binding in determining
      how these GTPases evolved specific functions at distinct stages of polarized
      growth.

PMID- 20823268
TI  - The mitogen-activated protein kinase Slt2 regulates nuclear retention of non-heat
      shock mRNAs during heat shock-induced stress.
AB  - Cellular adaptation to environmental stress conditions requires rapid and
      specific changes in gene expression. During heat shock, most polyadenylated mRNAs
      are retained in the nucleus, whereas the export of heat shock-induced mRNAs is
      allowed. Although essential mRNA export factors are known, the precise mechanism
      for regulating transport is not fully understood. Here we find that during heat
      shock in Saccharomyces cerevisiae, the mRNA-binding protein Nab2 is
      phosphorylated on threonine 178 and serine 180 by the mitogen-activated protein
      (MAP) kinase Slt2/Mpk1. Slt2 is required for nuclear poly(A(+)) mRNA accumulation
      upon heat shock, and thermotolerance is decreased in a nup42 nab2-T178A/S180A
      mutant. Coincident with phosphorylation, Nab2 and Yra1 colocalize in nuclear foci
      with Mlp1, a protein involved in mRNA retention. Nab2 nuclear focus formation and
      Nab2 phosphorylation are independent, suggesting that heat shock induces multiple
      cellular alterations that impinge upon transport efficiency. Under normal
      conditions, we find that the mRNA export receptor Mex67 and Nab2 directly
      interact. However, upon heat shock stress, Mex67 does not localize to the Mlp1
      nuclear foci, and its association with Nab2 complexes is reduced. These results
      reveal a novel mechanism by which the MAP kinase Slt2 and Mlp1 control mRNA
      export factors during heat shock stress.

PMID- 20823270
TI  - An upstream open reading frame and the context of the two AUG codons affect the
      abundance of mitochondrial and nuclear RNase H1.
AB  - RNase H1 in mammalian cells is present in nuclei and mitochondria. Its absence in
      mitochondria results in embryonic lethality due to the failure to amplify
      mitochondrial DNA (mtDNA). Dual localization to mitochondria and nuclei results
      from differential translation initiation at two in-frame AUGs (M1 and M27) of a
      single mRNA. Here we show that expression levels of the two isoforms depend on
      the efficiency of translation initiation at each AUG codon and on the presence of
      a short upstream open reading frame (uORF) resulting in the mitochondrial isoform
      being about 10% as abundant as the nuclear form. Translation initiation at the M1
      AUG is restricted by the uORF, while expression of the nuclear isoform requires
      reinitiation of ribosomes at the M27 AUG after termination of uORF translation or
      new initiation by ribosomes skipping the uORF and the M1 AUG. Such translational
      organization of RNase H1 allows tight control of expression of RNase H1 in
      mitochondria, where its excess or absence can lead to cell death, without
      affecting the expression of the nuclear RNase H1.

PMID- 20823271
TI  - Regulation of eukaryotic initiation factor 4E (eIF4E) phosphorylation by mitogen
      activated protein kinase occurs through modulation of Mnk1-eIF4G interaction.
AB  - The m(7)G cap binding protein eukaryotic initiation factor 4E (eIF4E) is a rate
      limiting determinant of protein synthesis. Elevated eIF4E levels, commonly
      associated with neoplasia, promote oncogenesis, and phosphorylation of eIF4E at
      Ser209 is critical for its tumorigenic potential. eIF4E phosphorylation is
      catalyzed by mitogen-activated protein kinase (MAPK)-interacting serine/threonine
      kinase (Mnk), a substrate of Erk1/2 and p38 MAPKs. Interaction with the
      scaffolding protein eIF4G, which also binds eIF4E, brings Mnk and its substrate
      into physical proximity. Thus, Mnk-eIF4G interaction is important for eIF4E
      phosphorylation. Through coimmunoprecipitation assays, we showed that MAPK
      mediated phosphorylation of the Mnk1 active site controls eIF4G binding.
      Utilizing a naturally occurring splice variant, we demonstrated that the C
      terminal domain of Mnk1 restricts its interaction with eIF4G, preventing eIF4E
      phosphorylation in the absence of MAPK signaling. Furthermore, using a small
      molecule Mnk1 inhibitor and kinase-dead mutant, we established that Mnk1
      autoregulates its interaction with eIF4G, releasing itself from the scaffold
      after phosphorylation of its substrate. Our findings indicate tight control of
      eIF4E phosphorylation through modulation of Mnk1-eIF4G interaction.

PMID- 20823272
TI  - Protein arginine methylation facilitates cotranscriptional recruitment of pre
      mRNA splicing factors.
AB  - Cotranscriptional recruitment of pre-mRNA splicing factors to their genomic
      targets facilitates efficient and ordered assembly of a mature messenger
      ribonucleoprotein particle (mRNP). However, how the cotranscriptional recruitment
      of splicing factors is regulated remains largely unknown. Here, we demonstrate
      that protein arginine methylation plays a novel role in regulating this process
      in Saccharomyces cerevisiae. Our data show that Hmt1, the major type I arginine
      methyltransferase, methylates Snp1, a U1 small nuclear RNP (snRNP)-specific
      protein, and that the mammalian Snp1 homolog, U1-70K, is likewise arginine
      methylated. Genome-wide localization analysis reveals that the deletion of the
      HMT1 gene deregulates the recruitment of U1 snRNP and its associated components
      to intron-containing genes (ICGs). In the same context, splicing factors acting
      downstream of U1 snRNP addition bind to a reduced number of ICGs. Quantitative
      measurement of the abundance of spliced target transcripts shows that these
      changes in recruitment result in an increase in the splicing efficiency of
      developmentally regulated mRNAs. We also show that in the absence of either Hmt1
      or of its catalytic activity, an association between Snp1 and the SR-like protein
      Npl3 is substantially increased. Together, these data support a model whereby
      arginine methylation modulates dynamic associations between SR-like protein and
      pre-mRNA splicing factor to promote target specificity in splicing.

PMID- 20823273
TI  - Sub1 globally regulates RNA polymerase II C-terminal domain phosphorylation.
AB  - The transcriptional coactivator Sub1 has been implicated in several aspects of
      mRNA metabolism in yeast, such as activation of transcription, termination, and
      3'-end formation. Here, we present evidence that Sub1 plays a significant role in
      controlling phosphorylation of the RNA polymerase II large subunit C-terminal
      domain (CTD). We show that SUB1 genetically interacts with the genes encoding all
      four known CTD kinases, SRB10, KIN28, BUR1, and CTK1, suggesting that Sub1 acts
      to influence CTD phosphorylation at more than one step of the transcription
      cycle. To address this directly, we first used in vitro kinase assays, and we
      show that, on the one hand, SUB1 deletion increased CTD phosphorylation by Kin28,
      Bur1, and Ctk1 but, on the other, it decreased CTD phosphorylation by Srb10.
      Second, chromatin immunoprecipitation assays revealed that SUB1 deletion
      decreased Srb10 chromatin association on the inducible GAL1 gene but increased
      Kin28 and Ctk1 chromatin association on actively transcribed genes. Taken
      together, our data point to multiple roles for Sub1 in the regulation of CTD
      phosphorylation throughout the transcription cycle.

PMID- 20823274
TI  - Symplekin specifies mitotic fidelity by supporting microtubule dynamics.
AB  - Using a pangenomic loss-of-function screening strategy, we have previously
      identified 76 potent modulators of paclitaxel responsiveness in non-small-cell
      lung cancer. The top hit isolated from this screen, symplekin, is a well
      established component of the mRNA polyadenylation machinery. Here, we performed a
      high-resolution phenotypic analysis to reveal the mechanistic underpinnings by
      which symplekin depletion collaborates with paclitaxel. We find that symplekin
      supports faithful mitosis by contributing to the formation of a bipolar spindle
      apparatus. Depletion of symplekin attenuates microtubule polymerization activity
      as well as expression of the critical microtubule polymerization protein CKAP5
      (TOGp). Depletion of additional members of the polyadenylation complex induces
      similar phenotypes, suggesting that polyadenylation machinery is intimately
      coupled to microtubule function and thus mitotic spindle formation. Importantly,
      tumor cells depleted of symplekin display reduced fecundity, but the mitotic
      defects that we observe are not evident in immortalized cells. These results
      demonstrate a critical connection between the polyadenylation machinery and
      mitosis and suggest that tumor cells have an enhanced dependency on these
      components for spindle assembly.

PMID- 20823275
TI  - Expression of skeletal muscle sodium channel (Nav1.4) or connexin32 prevents
      reperfusion arrhythmias in murine heart.
AB  - AIMS: acute myocardial ischaemia induces a decrease in resting membrane potential
      [which leads to reduction of action potential (AP) V(max)] and intracellular
      acidification (which closes gap junctions). Both contribute to conduction
      slowing. We hypothesized that ventricular expression of the skeletal muscle Na(+)
      channel, Nav1.4 (which activates fully at low membrane potentials), or connexin32
      (Cx32, which is less pH-sensitive than connexin43) would support conduction and
      be antiarrhythmic. We tested this hypothesis in a murine model of ischaemia and
      reperfusion arrhythmias. METHODS AND RESULTS: empty adenovirus (Sham) or
      adenoviral constructs expressing either SkM1 (gene encoding Nav1.4) or Cx32 genes
      were injected into the left ventricular wall. Four days later, ventricular
      tachycardia (VT) occurred during reperfusion following a 5 min coronary
      occlusion. In Nav1.4- and Cx32-expressing mice, VT incidence and duration were
      lower than in Sham (P < 0.05). In vitro multisite microelectrode mapping was
      performed in the superfused right ventricular wall. To simulate ischaemic
      conditions, [K(+)] in solution was increased to 10 mmol/L and/or pH was decreased
      to 6.0. Western blots revealed Cx32 and Nav1.4 expression in both ventricles.
      Nav1.4 APs showed higher V(max) and conduction velocity (CV) than Shams at normal
      and elevated [K(+)]. Exposure of tissue to acid solution reduced intracellular pH
      to 6.4. There was no difference in CV between Sham and Cx32 groups in control
      solution. Acid solution slowed CV in Sham (P < 0.05) but not in Cx32. CONCLUSION:
      Nav1.4 or Cx32 expression preserved normal conduction in murine hearts and
      decreased the incidence of reperfusion VT.

PMID- 20823276
TI  - Membrane raft-lysosome redox signalling platforms in coronary endothelial
      dysfunction induced by adipokine visfatin.
AB  - AIMS: The adipokine visfatin, produced during obesity, has been reported to
      participate in the development of cardiovascular disease associated with
      metabolic syndrome. The present study was designed to test a hypothesis that
      visfatin causes coronary endothelial dysfunction through lysosome trafficking and
      fusion to cell membranes, membrane raft (MR) clustering, and formation of redox
      signalosomes. METHODS AND RESULTS: By using confocal microscopy, it was found
      that visfatin, but not adiponectin, stimulated NADPH oxidase (NOX) subunits,
      gp91(phox) aggregation in MR clusters and p47(phox) translocation to these MR
      clusters in bovine coronary arterial endothelial cells (CAECs), leading to
      activation of NOX with a 2.5-fold increase in O(2)(.-) production. A signalling
      lipid, ceramide, was found to be enriched in such membrane MR-NOX complexes of
      CAECs. Lysosomal fluorescent dye (FM1-43) quenching and de-quenching revealed
      that visfatin induced the fusion of lysosomes to cell membranes and incorporation
      of acid sphingomyelinase and its product, ceramide, in such MR-NOX signalling
      platforms. Functionally, visfatin significantly attenuated endothelium-dependent
      vasodilation in small coronary arteries (by 80%), which was blocked by lysosomal
      function inhibitor and MR disruptors. CONCLUSION: These results suggest that
      lysosome-associated molecular trafficking and consequent ceramide accumulation in
      cell membrane may mediate the assembly of NOX subunits and their activation in
      response to adipokine visfatin in CAECs, thereby producing endothelial
      dysfunction in coronary circulation.

PMID- 20823277
TI  - Lysine deacetylation in ischaemic preconditioning: the role of SIRT1.
AB  - AIMS: Acute ischaemic preconditioning (IPC) induces protection against cardiac
      ischaemia-reperfusion (IR) via post-translational modification of key proteins.
      Lysine (Lys) acetylation is an important regulator of protein function, but this
      type of modification has not been studied in the context of IPC. We investigated
      Lys acetylation in IPC and its upstream regulation by SIRT1. METHODS AND RESULTS:
      Hearts from C57BL/6 mice were Langendorff-perfused and subjected to IPC and IR
      injury. Mice were exposed to IPC by in vivo coronary artery occlusion. An
      isolated cardiomyocyte model of IPC was also developed. Lys acetylation was
      measured by western blotting, and pharmacological modulators of Lys acetylation
      were tested. More Lys deacetylation was observed in IPC, in the Langendorff, in
      vivo, and cellular IPC models; this was concurrent with an increase in SIRT1
      activity measured by p53 Lys379 deacetylation. IPC was not accompanied by changes
      in SIRT1 protein level, but evidence was obtained for SIRT1 modification by Small
      Ubiquitin-like Modifier (SUMOylation) in IPC. Furthermore, the specific SIRT1
      inhibitor splitomicin reversed both IPC-mediated Lys deacetylation and IPC
      induced cardioprotection. Inhibition of nicotinamide phosphoribosyltransferase
      (Nampt, an important enzyme which regulates SIRT1 activity by maintaining
      availability of the substrate NAD(+)) also blocked both IPC-induced deacetylation
      and cardioprotection. CONCLUSION: Lys deacetylation occurs during IPC and an
      elevation in SIRT1 activity plays a role in this phenomenon. Inhibition of SIRT1,
      either directly or by restricting the availability of its substrate NAD(+),
      inhibits IPC. Together these data suggest a role for SIRT1-mediated Lys
      deacetylation in the mechanism of acute IPC.

PMID- 20823278
TI  - Brucellosis-induced autoimmune hemolytic anemia treated with rituximab.
AB  - OBJECTIVE: To present a case of brucellosis-induced severe autoimmune hemolytic
      anemia (AIHA) that was refractory to traditional corticosteroid treatment and
      eventually treated with rituximab apart from antibiotic therapy and to discuss
      the potential role of rituximab in similar cases of AIHA triggered by an
      underlying reversible cause. CASE SUMMARY: A 79-year-old woman was diagnosed with
      severe AIHA (reticulocyte count 21.5%, hemoglobin 6 g/dL). Initial treatment with
      prednisone in a regional hospital was not efficacious. Brucellosis was diagnosed
      by serology; the disease was further complicated by hepatic and splenic
      granulomatous involvement and sacral bone localization. Due to the severity of
      AIHA as demonstrated by reticulocyte count and hemoglobin levels, the initial
      unresponsiveness to corticosteroid therapy, the potential of the underlying
      infectious cause to relapse along with AIHA, and the localization of the pathogen
      in a focal site (bone involvement) that could act as a constant AIHA trigger, the
      patient was treated aggressively with rituximab, apart from the typical
      antimicrobial therapy. DISCUSSION: Brucellosis can induce autoimmunity and mimic
      primary hematologic diseases. We reviewed reports on the unique forms of Brucella
      induced hemolysis available in the literature. Massive hemolysis, though, is
      rare, and in the case of a pathogen such as brucellosis, one cannot ignore the
      potential for infection relapse accompanied by hemolysis relapse. Cases
      refractory to corticosteroids are typically treated with invasive amputative
      procedures such as splenectomy. However, in cases where an underlying
      therapeutically reversible cause of infection can be identified, the proven short
      term efficacy and safety profile of rituximab can be of significance.
      CONCLUSIONS: Novel therapeutic approaches with molecular agents such as rituximab
      may assist in treatment of considerably severe infectious pathogen-induced
      autoimmune hemolytic anemia that is refractory to first-line therapy.

PMID- 20823279
TI  - Trimethoprim/Sulfamethoxazole pharmacokinetics in two patients undergoing
      continuous venovenous hemodiafiltration.
AB  - OBJECTIVE: To determine the extent of elimination of trimethoprim (TMP) and
      sulfamethoxazole (SMX) via continuous venovenous hemodiafiltration (CVVHDF) in 2
      critically ill patients with renal failure. CASE SUMMARY: A 62-year-old woman
      with Pneumocystis jirovecii pneumonia (PCP) was admitted to our intensive care
      unit for severe acute respiratory distress syndrome. A 77-year-old man was
      admitted for aortic root replacement and developed septic shock and nosocomial
      pneumonia due to Stenotrophomonas maltophilia. Both patients developed acute
      renal failure, necessitating CVVHDF. They were treated with intravenous TMP/SMX
      adapted to renal function. The first patient received TMP 6.4 mg/kg/day and SMX
      32 mg/kg/day, corresponding to 50% of the recommended high-dose TMP/SMX regimen
      in PCP patients. The second patient received TMP 1.7 mg/kg/day and SMX 8.6
      mg/kg/day, corresponding to 50% of the usual dose in bacterial infections. We
      determined peak and trough serum TMP and SMX concentrations and the extent of
      TMP/SMX CVVHDF clearance at steady-state while the patients were still anuric and
      oliguric. DISCUSSION: Data on TMP and SMX pharmacokinetics in CVVHDF are lacking
      and dosing recommendations are inconclusive. In both patients, CVVHDF clearance
      of TMP ranged from 21.5 to 28.9 mL/min, corresponding with normal renal clearance
      (20-80 mL/min). SMX clearance in CVVHDF showed high variability (18.7, 26.7, and
      42.6 mL/min) and exceeded renal clearance values in normal renal function (1-5
      mL/min). Accordingly, peak TMP serum concentrations were within the recommended
      range in the patient treated with a reduced TMP/SMX dose for PCP, whereas her SMX
      peak concentrations were only one third of recommended target concentrations.
      CONCLUSIONS: Our data indicate that both TMP and SMX are removed by CVVHDF to a
      significant degree, and dose reduction of TMP/SMX in CVVHDF bears the risk of
      underdosing. Given variability in drug exposure in critically ill patients,
      therapeutic drug monitoring is advisable in anuric or oliguric patients
      undergoing continuous renal replacement therapy to ensure optimal TMP/SMX dosing.

PMID- 20823280
TI  - Echocardiography in aortic diseases: EAE recommendations for clinical practice.
AB  - Echocardiography plays an important role in the diagnosis and follow-up of aortic
      diseases. Evaluation of the aorta is a routine part of the standard
      echocardiographic examination. Transthoracic echocardiography (TTE) permits
      adequate assessment of several aortic segments, particularly the aortic root and
      proximal ascending aorta. Transoesophageal echocardiography (TOE) overcomes the
      limitations of TTE in thoracic aorta assessment. TTE and TOE should be used in a
      complementary manner. Echocardiography is useful for assessing aortic size,
      biophysical properties, and atherosclerotic involvement of the thoracic aorta.
      Although TOE is the technique of choice in the diagnosis of aortic dissection,
      TTE may be used as the initial modality in the emergency setting. Intimal flap in
      proximal ascending aorta, pericardial effusion/tamponade, and left ventricular
      function can be easily visualized by TTE. However, a negative TTE does not rule
      out aortic dissection and other imaging techniques must be considered. TOE should
      define entry tear location, mechanisms and severity of aortic regurgitation, and
      true lumen compression. In addition, echocardiography is essential in selecting
      and monitoring surgical and endovascular treatment and in detecting possible
      complications. Although other imaging techniques such as computed tomography and
      magnetic resonance have a greater field of view and may yield complementary
      information, echocardiography is portable, rapid, accurate, and cost-effective in
      the diagnosis and follow-up of most aortic diseases.

PMID- 20823281
TI  - Relationship between meniscal extrusion and various clinical findings after
      meniscus allograft transplantation.
AB  - BACKGROUND: Meniscus allograft transplantation (MAT) is useful for meniscus
      deficient knees. Although meniscal extrusion is common after MAT, there is no
      consensus regarding the criteria for normal meniscal extrusion or the
      relationship between clinical and radiologic results. HYPOTHESIS: Meniscal
      extrusion after MAT results in poor clinical, radiologic, and arthroscopic
      outcomes. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Thirty-six of
      60 patients undergoing MAT from September 2002 to June 2007 who were available
      for follow-up evaluation for more than 2 years were evaluated. The study
      population (31 men, 5 women) consisted of 15 and 21 cases of medial and lateral
      meniscus transplant, respectively. Knee status was evaluated by Lysholm score,
      plain radiography, and magnetic resonance imaging preoperatively and
      postoperatively. Second-look examinations were performed in 18 cases. RESULTS:
      Mean follow-up was 31.4 months (range, 24-36). Lysholm knee score increased
      significantly (mean, 88.2; range, 70-100) on final visit versus the preoperative
      value (mean, 61.2; range, 26-83; P < .001). Joint-space narrowing was 0.08 mm
      (range, -2.58 to 1.92) in extension AP and -0.09 mm (range, -2.3 to 1.8) in
      Rosenberg view. Kellgren-Lawrence arthrosis grade did not change in 28 knees
      (77.8%) and progressed by 1 grade in 8 knees. Meniscal extrusion extent was 3.87
      +/- 1.94 mm and relative percentage extrusion was 42.1% +/- 17.7%. Seven cases
      (19.4%) showed minor extrusion (<3 mm), 27 (75%) showed major extrusion (>3 mm),
      and 2 (5.6%) showed no extrusion. Further degeneration was absent in 28 knees
      (77.8%) on magnetic resonance imaging. In second-look arthroscopic examinations
      at an average of 26.3 months, 11 of 18 (63.6%) cases showed no progression of
      cartilage degeneration. There was no significant correlation between meniscal
      extrusion and other parameters. CONCLUSION: This study indicated that MAT can
      improve the clinical status of the meniscectomized knee. Although meniscal
      extrusion occurred after surgery in most cases, there was no significant
      correlation with various clinical, radiologic, or arthroscopic outcomes. Further
      studies are required to evaluate long-term effects of meniscal extrusion.

PMID- 20823282
TI  - Pharmacokinetics and pharmacogenomics of once-daily raltegravir and atazanavir in
      healthy volunteers.
AB  - Atazanavir inhibits UDP-glucuronyl-transferase-1A1 (UGT1A1), which metabolizes
      raltegravir, but the magnitude of steady-state inhibition and role of the UGT1A1
      genotype are unknown. Sufficient inhibition could lead to reduced-dose and -cost
      raltegravir regimens. Nineteen healthy volunteers, age 24 to 51 years, took
      raltegravir 400 mg twice daily (arm A) and 400 mg plus atazanavir 400 mg once
      daily (arm B), separated by >=3 days, in a crossover design. After 1 week on each
      regimen, raltegravir and raltegravir-glucuronide plasma and urine concentrations
      were measured by liquid chromatography-tandem mass spectrometry in multiple
      samples obtained over 12 h (arm A) or 24 h (arm B) and analyzed by
      noncompartmental methods. UGT1A1 promoter variants were detected with a
      commercially available kit and published primers. The primary outcome was the
      ratio of plasma raltegravir C(tau), or concentration at the end of the dosing
      interval, for arm B (24 h) versus arm A (12 h). The arm B-to-arm A geometric mean
      ratios (95% confidence interval, P value) for plasma raltegravir C(tau), area
      under the concentration-time curve from 0 to 12 h (AUC(0-12)), and raltegravir
      glucuronide/raltegravir AUC(0-12) were 0.38 (0.22 to 0.65, 0.001), 1.32 (0.62 to
      2.81, 0.45), and 0.47 (0.38 to 0.59, <0.001), respectively. Nine volunteers were
      heterozygous and one was homozygous for a UGT1A1 reduction-of-function allele,
      but these were not associated with metabolite formation. Although atazanavir
      significantly reduced the formation of the glucuronide metabolite, its steady
      state boosting of plasma raltegravir did not render the C(tau) with a once-daily
      raltegravir dose of 400 mg similar to the C(tau) with the standard twice-daily
      dose. UGT1A1 promoter variants did not significantly influence this interaction.

PMID- 20823283
TI  - Mutational analysis of flucytosine resistance in Candida glabrata.
AB  - The antifungal flucytosine (5-fluorocytosine [5FC]) is a prodrug metabolized to
      its toxic form, 5-fluorouracil (5FU), only by organisms expressing cytosine
      deaminase. One such organism is Candida glabrata, which has emerged as the second
      most common agent of bloodstream and mucosal candidiasis. This emergence has been
      attributed to the high rate at which C. glabrata develops resistance to azole
      antifungals. As an oral agent, 5FC represents an attractive alternative or
      complement to azoles; however, the frequency of 5FC resistance mutations and the
      mechanisms by which these mutations confer resistance have been explored only
      minimally. On RPMI 1640 medium containing 1 MUg/ml 5FC (32-fold above the MIC,
      but less than 1/10 of typical serum levels), resistant mutants occurred at a
      relatively low frequency (2 * 10-7). Three of six mutants characterized were 5FU
      cross-resistant, suggesting a mutation downstream of the Fcy1 gene (cytosine
      deaminase), which was confirmed by sequence analysis of the Fur1 gene (uracil
      phosphoribosyl transferase). The remaining three mutants had Fcy1 mutations. To
      ascertain the effects of 5FC resistance mutations on enzyme function, mutants
      were isolated in ura3 strains. Three of seven mutants harbored Fcy1 mutations and
      failed to grow in uridine-free, cytosine-supplemented medium, consistent with
      inactive Fcy1. The remainder grew in this medium and had wild-type Fcy1; further
      analysis revealed these to be mutated in the Fcy2L homolog of S. cerevisiae Fcy2
      (purine-cytosine transporter). Based on this analysis, we characterized three 5FC
      resistant clinical isolates, and mutations were identified in Fur1 and Fcy1.
      These data provide a framework for understanding 5FC resistance in C. glabrata
      and potentially in other fungal pathogens.

PMID- 20823284
TI  - Preclinical characterization of BI 201335, a C-terminal carboxylic acid inhibitor
      of the hepatitis C virus NS3-NS4A protease.
AB  - BI 201335 is a hepatitis C virus (HCV) NS3-NS4A (NS3 coexpressed with NS4A)
      protease inhibitor that has been shown to have potent clinical antiviral
      activity. It is a highly optimized noncovalent competitive inhibitor of full
      length NS3-NS4A proteases of HCV genotypes 1a and 1b with K(i) values of 2.6 and
      2.0 nM, respectively. K(i) values of 2 to 230 nM were measured against the NS3
      NS4A proteases of HCV genotypes 2 to 6, whereas it was a very weak inhibitor of
      cathepsin B and showed no measurable inhibition of human leukocyte elastase. BI
      201335 was also shown to be a potent inhibitor of HCV RNA replication in vitro
      with 50% effective concentrations (EC(50)s) of 6.5 and 3.1 nM obtained in
      genotype 1a and 1b replicon assays. Combinations of BI 201335 with either
      interferon or ribavirin had additive effects in replicon assays. BI 201335 had
      good permeability in Caco-2 cell assays and high metabolic stability after
      incubation with human, rat, monkey, and dog liver microsomes. Its good
      absorption, distribution, metabolism, and excretion (ADME) profile in vitro, as
      well as in rat, monkey, and dog, predicted good pharmacokinetics (PK) in humans.
      Furthermore, drug levels were significantly higher in rat liver than in plasma,
      suggesting that distribution to the target organ may be especially favorable. BI
      201335 is a highly potent and selective NS3-NS4A protease inhibitor with good in
      vitro and animal ADME properties, consistent with its good human PK profile, and
      shows great promise as a treatment for HCV infection.

PMID- 20823285
TI  - Importance of infusion volume and pump characteristics in extended administration
      of beta-lactam antibiotics.

PMID- 20823286
TI  - Tolerance of benznidazole in treatment of Chagas' disease in adults.
AB  - Chagas' disease is an emerging public health problem in areas where the disease
      is not endemic. Treatment with benznidazole has shown efficacy in the acute stage
      of the disease, but its efficacy in the chronic stage remains controversial, and
      unwanted side effects are more frequent and severe in adults than in children.
      This study describes the profile of side effects of benznidazole in a cohort of
      Trypanosoma cruzi-infected patients in a European country.

PMID- 20823287
TI  - Amikacin monotherapy for sepsis caused by panresistant Pseudomonas aeruginosa.
AB  - Two patients with severe sepsis due to panresistant Pseudomonas aeruginosa,
      deteriorating despite therapy with colistin and beta-lactams, were cured with a
      high daily dose (25 to 50 mg/kg) of amikacin to obtain a peak/MIC ratio of at
      least 8 to 10 (MIC = 16 MUg/ml). Concomitant use of continuous venovenous
      hemodiafiltration (CVVHDF) provided no deterioration in renal function after
      treatment. High dosage of aminoglycosides combined with CVVHDF may represent a
      valuable therapeutic option for infection due to multiresistant pathogens.

PMID- 20823289
TI  - Emergence of metallo-beta-lactamase NDM-1-producing multidrug-resistant
      Escherichia coli in Australia.
AB  - A multidrug-resistant Escherichia coli isolate recovered in Australia produced a
      carbapenem-hydrolyzing beta-lactamase. Molecular investigations revealed the
      first identification of the bla(NDM-1) metallo-beta-lactamase gene in that
      country. In addition, this E. coli isolate expressed the extended-spectrum beta
      lactamase CTX-M-15, together with two 16S rRNA methylases, namely, ArmA and RmtB,
      conferring a high level of resistance to aminoglycosides.

PMID- 20823288
TI  - Hexadecyloxypropyl-cidofovir (CMX001) suppresses JC virus replication in human
      fetal brain SVG cell cultures.
AB  - JC virus (JCV) is a polyomavirus that infects human oligodendrocytes, leading to
      development of progressive multifocal leukoencephalopathy (PML), an often fatal
      demyelinating disease occurring in immunocompromised individuals. Currently there
      are no effective therapies for the treatment of PML that result in clearance of
      JCV from the brain. Cidofovir (CDV) is an acyclic nucleoside phosphonate that
      inhibits DNA polymerases and has been used for the treatment of PML. However, CDV
      demonstrated little efficacy as a treatment for PML and causes substantial side
      effects to patients. To improve efficacy and reduce the toxicity of CDV, a lipid
      ester derivative, CMX001, was generated by Chimerix and is currently in
      multicenter phase II clinical trials for the prevention or control of
      cytomegalovirus infection in hematopoietic stem cell transplant recipients and of
      BK virus in the urine of stem cell or renal allograft recipients. CMX001 caused
      minimal cytotoxic effects in human fetal brain SVG cells when used at
      concentrations between 0.01 MUM and 0.1 MUM. CMX001 resulted in a dose-dependent
      decrease in the number of JCV-infected cells during initial infection and nearly
      eliminated JCV-infected cells during an established infection. In addition,
      CMX001 treatment resulted in a 60% reduction in JCV DNA copy number during
      initial infection, which suggests that suppression of JCV infection by CMX001 is
      likely due to inhibition of virus DNA replication. This study demonstrates that
      CMX001 suppresses JCV infection at concentrations that have limited toxicity to
      human brain cells, indicating its potential use to limit JCV replication in
      infected patients.

PMID- 20823290
TI  - Pharmacokinetics-pharmacodynamics of a respiratory syncytial virus fusion
      inhibitor in the cotton rat model.
AB  - Human respiratory syncytial virus (RSV) is a major cause of lower respiratory
      tract infections in infants, young children, elderly persons, and severely
      immunocompromised patients. Effective postinfection treatments are not widely
      available, and currently there is no approved vaccine. TMC353121 is a potent RSV
      fusion inhibitor in vitro, and its ability to reduce viral loads in vivo was
      demonstrated in cotton rats following prophylactic intravenous administration.
      Here, the pharmacokinetics of TMC353121 in the cotton rat, which is
      semipermissive for RSV replication, were further explored to build a
      pharmacokinetic-pharmacodynamic (PK-PD) model and to estimate the plasma drug
      levels needed for significant antiviral efficacy. TMC353121 reduced the viral
      titers in bronchoalveolar lavage fluid in a dose-dependent manner after a single
      subcutaneous administration and intranasal RSV inoculation 24 h after compound
      administration. The viral titer reduction and plasma TMC353121 concentration at
      the time of RSV inoculation were well described using a simple E(max) model with
      a maximal viral titer reduction (E(max)) of 1.5 log(10). The plasma drug level
      required to achieve 50% of the E(max) (200 ng/ml) was much higher than the 50%
      inhibitory concentration observed in vitro in HeLaM cells (0.07 ng/ml). In
      conclusion, this simple PK-PD approach may be useful in predicting efficacious
      exposure levels for future RSV inhibitors.

PMID- 20823292
TI  - Effect of immune complex formation on the distribution of a novel antibody to the
      ovarian tumor antigen CA125.
AB  - 3A5 is a novel antibody that binds repeated epitopes within CA125, an ovarian
      tumor antigen that is shed into the circulation. Binding to shed antigen may
      limit the effectiveness of therapeutic antibodies because of unproductive immune
      complex (IC) formation and/or altered antibody distribution. To evaluate this
      possibility, we characterized the impact of shed CA125 on the in vivo
      distribution of 3A5. In vitro, 3A5 and CA125 were found to form ICs in a
      concentration-dependent manner. This phenomenon was then evaluated in vivo using
      quantitative whole-body autoradiography to assess the tissue distribution of
      (125)I-3A5 in an orthotopic OVCAR-3 tumor mouse model at different stages of
      tumor burden. Low doses of 3A5 (75 MUg/kg) and pathophysiological levels of shed
      CA125 led to the formation of ICs in vivo that were rapidly distributed to the
      liver. Under these conditions, increased clearance of 3A5 from normal tissues was
      observed in mice bearing CA125-expressing tumors. Of importance, despite IC
      formation, 3A5 uptake by tumors was sustained over time. At a therapeutically
      relevant dose of 3A5 (3.5 mg/kg), IC formation was undetectable and distribution
      to normal tissues followed that of blood. In contrast, increased levels of
      radioactivity were observed in the tumors. These data demonstrate that CA125 and
      3A5 do form ICs in vivo and that the liver is involved in their uptake. However,
      at therapeutic doses of 3A5 and clinically relevant CA125 levels, IC formation
      consumes only a minor fraction of 3A5, and tumor targeting seems to be
      unaffected.

PMID- 20823291
TI  - Diet-induced obesity accelerates acute lymphoblastic leukemia progression in two
      murine models.
AB  - Obesity is associated with an increased incidence of many cancers, including
      leukemia, although it is unknown whether leukemia incidence is increased directly
      by obesity or rather by associated genetic, lifestyle, health, or socioeconomic
      factors. We developed animal models of obesity and leukemia to test whether
      obesity could directly accelerate acute lymphoblastic leukemia (ALL) using
      BCR/ABL transgenic and AKR/J mice weaned onto a high-fat diet. Mice were observed
      until development of progressive ALL. Although obese and control BCR/ABL mice had
      similar median survival, older obese mice had accelerated ALL onset, implying a
      time-dependent effect of obesity on ALL. Obese AKR mice developed ALL
      significantly earlier than controls. The effect of obesity was not explained by
      WBC count, thymus/spleen weight, or ALL phenotype. However, obese AKR mice had
      higher leptin, insulin, and interleukin-6 levels than controls, and these obesity
      related hormones all have potential roles in leukemia pathogenesis. In
      conclusion, obesity directly accelerates presentation of ALL, likely by
      increasing the risk of an early event in leukemogenesis. This is the first study
      to show that obesity can directly accelerate the progression of ALL. Thus, the
      observed associations between obesity and leukemia incidence are likely to be
      directly related to biological effects of obesity.

PMID- 20823293
TI  - Antigen-dependent internalization is related to rapid elimination from plasma of
      humanized anti-HM1.24 monoclonal antibody.
AB  - Anti-HM1.24 monoclonal antibody (AHM) is a humanized anti-HM1.24 monoclonal
      antibody that binds to the HM1.24 antigen, a protein that is highly expressed in
      multiple myeloma cells. The pharmacokinetics of AHM was determined in experiments
      in which AHM was administered intravenously to cynomolgus monkeys. The area under
      the plasma concentration-time curve increased by more than the dose ratio between
      2 and 20 mg/kg, and nonlinear pharmacokinetics was observed. The elimination half
      life of AHM from the plasma was 7.56 h at 2 mg/kg and 28.6 h at 20 mg/kg, which
      was shorter than that observed for other therapeutic humanized monoclonal
      antibodies, such as trastuzumab and bevacizumab. Although antibodies to AHM were
      detected in all monkeys on or after 10 days of administration, there was a
      temporal disassociation between the rapid elimination of AHM and the appearance
      of anti-AHM antibodies. HM1.24 antigen-dependent internalization and
      intracellular metabolism of AHM were investigated in peripheral blood
      mononuclear, KPMM2, and U937 cells. In all cases, AHM was rapidly internalized
      from the cell surface; this internalization was significantly prevented by
      phenylarsine oxide in KPMM2 cells, an inhibitor of receptor-mediated endocytosis,
      and the internalized AHM was subsequently degraded within the cells. Furthermore,
      immunofluorescence microscopy revealed that the internalized AHM is delivered to
      and degraded in late endosomes/lysosomes. Taken together, our results suggest
      that the rapid elimination of AHM from plasma in monkey is due to HM1.24 antigen
      dependent internalization followed by delivery to the lysosomes.

PMID- 20823294
TI  - Involvement of carboxylesterase 1 and 2 in the hydrolysis of mycophenolate
      mofetil.
AB  - Mycophenolate mofetil (MMF) is the ester prodrug of the immunosuppressant agent
      mycophenolic acid (MPA) and is rapidly activated by esterases after oral
      administration. However, the role of isoenzymes in MMF hydrolysis remains
      unclear. Although human plasma, erythrocytes, and whole blood contain MMF
      hydrolytic activities, the mean half-lives of MMF in vitro were 15.1, 1.58, and
      3.20 h, respectively. Thus, blood esterases seemed to contribute little to the
      rapid MMF disappearance in vivo. In vitro analyses showed that human intestinal
      microsomes exposed to 5 and 10 MUM MMF exhibited hydrolytic activities of 2.38
      and 4.62 nmol/(min . mg protein), respectively. Human liver microsomes exhibited
      hydrolytic activities of 14.0 and 26.1 nmol/(min . mg protein), respectively,
      approximately 6-fold higher than those observed for intestinal microsomes. MMF
      hydrolytic activities in human liver cytosols were 1.40 and 3.04 nmol/(min . mg
      protein), respectively. Because hepatic cytosols generally contain 5-fold more
      protein than microsomes, MMF hydrolysis in human liver cytosols corresponded to
      approximately 50% of that observed in microsomes. Fractions obtained by 9000g
      centrifugation of supernatants from COS-1 cells expressing human carboxylesterase
      (CES) 1 or 2 exhibited MMF hydrolytic activity, with CES1-containing fractions
      showing higher catalytic efficiency than CES2-containing fractions. The CES
      inhibitor bis-p-nitrophenylphosphate inhibited MMF hydrolysis in human liver
      microsomes and cytosols with IC(50) values of 0.51 and 0.36 MUM, respectively. In
      conclusion, both intestinal and hepatic CESs and in particular CES1 may be
      involved in MMF hydrolysis and play important roles in MMF bioactivation. Hepatic
      CES1 activity levels may help explain the between-subject variability observed
      for MMF usage.

PMID- 20823295
TI  - Prediction of efficacious inhalation lung doses via the use of in silico lung
      retention quantitative structure-activity relationship models and in vitro
      potency screens.
AB  - Lung concentrations of a drug are expected to drive the pharmacodynamic response
      to local inflammation after inhalation delivery, and the only way of determining
      the efficacious dose has been to measure it directly in animal models. In this
      study, we present a method to predict efficacious lung doses after inhalation in
      a rat lipopolysaccharide challenge model from in silico predictions of lung
      concentration and in vitro measurements only. A quantitative structure-activity
      relationship (QSAR) model, based on calculated physical properties predicted the
      partitioning of 34 compounds between lung and plasma. Because it was observed
      that lung/plasma partitioning correlated with lung concentration, it was possible
      to use this relationship to predict lung concentration at a given dose and time
      point. Based on the pharmacokinetic-pharmacodynamic (PKPD) relationship observed,
      a minimal free lung concentration relative to potency to drive significant
      inhibition of neutrophilia was established. By using predicted lung
      concentrations, measured fraction unbound in plasma, and cellular potency, it was
      possible to estimate an inhaled lung dose that would be expected to achieve this
      target exposure. These predictions were made for 23 compounds, which were not
      part of the original QSAR training set, and all except one were predicted to
      within 3-fold of their measured values. This novel approach shows that by
      understanding PKPD relationships and drivers for lung affinity after inhalation
      dosing, it is possible to estimate in vivo lung doses required for efficacy. This
      methodology provides a useful screening tool to rank candidate compounds and
      minimizes the use of extensive animal testing.

PMID- 20823297
TI  - Aggressive, funny, and thirsty: a Motivational Inference Model (MIMO) approach to
      behavioral rebound.
AB  - Rebound of thoughts after thought suppression is widely documented. Much less is
      known about the effects of suppression on rebound of behavior. The current
      studies show that suppressing thoughts (Experiment 1 and 2) and suppressing
      behavior (Experiment 3) may cause rebound of behavior. In Experiment 1
      suppressing thoughts of thirst rebounded in enhanced drinking, in Experiment 2
      suppressing aggressive thoughts rebounded in subsequent aggression, and in
      Experiment 3 suppressing laughter rebounded in enhanced subsequent laughing.
      Supporting the Motivational Inference Model of postsuppressional rebound, the
      studies show that behavioral rebound is reduced if participants are led to
      believe that suppression is difficult for everybody (Experiments 1 and 2). Also
      consistent with this model is the finding that motivation to do the suppressed
      behavior mediated rebound (Experiment 3). The implications for rebound of
      unwanted behaviors are discussed.

PMID- 20823296
TI  - Role of PTPRJ genotype in papillary thyroid carcinoma risk.
AB  - The strong genetic predisposition to papillary thyroid carcinoma (PTC) might be
      due to a combination of low-penetrance susceptibility variants. Thus, the
      research into gene variants involved in the increase of susceptibility to PTC is
      a relevant field of investigation. The gene coding for the receptor-type tyrosine
      phosphatase PTPRJ has been proposed as a cancer susceptibility gene, and its role
      as a tumor suppressor gene is well established in thyroid carcinogenesis. In this
      study, we want to ascertain the role of PTPRJ genotype in the risk for PTC. We
      performed a case-control study in which we determined the PTPRJ genotype for the
      non-synonymous Gln276Pro and Asp872Glu polymorphisms by PCR amplification and
      sequencing. We calculated allele and genotype frequencies for the considered
      polymorphisms of PTPRJ in a total sample of 299 cases (PTC patients) and 339
      controls (healthy subjects) selected from Caucasian populations. We observed a
      significantly higher frequency of homozygotes for the Asp872 allele in the group
      of PTC patients than in the control group (odds ratio=1.61, 95% confidence
      interval 1.15-2.25, P=0.0053). We observed a non-significant increased frequency
      of homozygotes for Gln276Pro polymorphism in PTC cases in two distinct Caucasian
      populations. Therefore, the results reported here show that the homozygous
      genotype for Asp872 of PTPRJ is associated with an increased risk to develop PTC.

PMID- 20823298
TI  - Automated construction and analysis of the design space for biochemical systems.
AB  - MOTIVATION: Our recent work introduced a generic method to construct the design
      space of biochemical systems: a representation of the relationships between
      system parameters, environmental variables and phenotypic behavior. In design
      space, the qualitatively distinct phenotypes of a biochemical system can be
      identified, counted, analyzed and compared. Boundaries in design space indicate a
      transition between phenotypic behaviors and can be used to measure a system's
      tolerance to large changes in parameters. Moreover, the relative size and
      arrangement of such phenotypic regions can suggest or confirm global properties
      of the system. RESULTS: Our work here demonstrates that the construction and
      analysis of design space can be automated. We present a formal description of
      design space and a detailed explanation of its construction. We also extend the
      notion to include variable kinetic orders. We describe algorithms that automate
      common steps of design space construction and analysis, introduce new analyses
      that are made possible by such automation and discuss challenges of
      implementation and scaling. In the end, we demonstrate the techniques using
      software we have created. AVAILABILITY: The Design Space Toolbox for MATLAB is
      freely available at http://www.bme.ucdavis.edu/savageaulab/ CONTACT:
      masavageau@ucdavis.edu

PMID- 20823300
TI  - Yves Moreau and Jaap Heringa, on behalf of the ECCB10 organizing and steering
      committees.

PMID- 20823301
TI  - A fast algorithm for exact sequence search in biological sequences using
      polyphase decomposition.
AB  - MOTIVATION: Exact sequence search allows a user to search for a specific DNA
      subsequence in a larger DNA sequence or database. It serves as a vital block in
      many areas such as Pharmacogenetics, Phylogenetics and Personal Genomics. As
      sequencing of genomic data becomes increasingly affordable, the amount of
      sequence data that must be processed will also increase exponentially. In this
      context, fast sequence search algorithms will play an important role in
      exploiting the information contained in the newly sequenced data. Many existing
      algorithms do not scale up well for large sequences or databases because of their
      high-computational costs. This article describes an efficient algorithm for
      performing fast searches on large DNA sequences. It makes use of hash tables of Q
      grams that are constructed after downsampling the database, to enable efficient
      search and memory use. Time complexity for pattern search is reduced using beam
      pruning techniques. Theoretical complexity calculations and performance figures
      are presented to indicate the potential of the proposed algorithm.

PMID- 20823302
TI  - Characteristics of 454 pyrosequencing data--enabling realistic simulation with
      flowsim.
AB  - MOTIVATION: The commercial launch of 454 pyrosequencing in 2005 was a milestone
      in genome sequencing in terms of performance and cost. Throughout the three
      available releases, average read lengths have increased to approximately 500 base
      pairs and are thus approaching read lengths obtained from traditional Sanger
      sequencing. Study design of sequencing projects would benefit from being able to
      simulate experiments. RESULTS: We explore 454 raw data to investigate its
      characteristics and derive empirical distributions for the flow values generated
      by pyrosequencing. Based on our findings, we implement Flowsim, a simulator that
      generates realistic pyrosequencing data files of arbitrary size from a given set
      of input DNA sequences. We finally use our simulator to examine the impact of
      sequence lengths on the results of concrete whole-genome assemblies, and we
      suggest its use in planning of sequencing projects, benchmarking of assembly
      methods and other fields. AVAILABILITY: Flowsim is freely available under the
      General Public License from http://blog.malde.org/index.php/flowsim/.

PMID- 20823303
TI  - Classification of ncRNAs using position and size information in deep sequencing
      data.
AB  - MOTIVATION: Small non-coding RNAs (ncRNAs) play important roles in various
      cellular functions in all clades of life. With next-generation sequencing
      techniques, it has become possible to study ncRNAs in a high-throughput manner
      and by using specialized algorithms ncRNA classes such as miRNAs can be detected
      in deep sequencing data. Typically, such methods are targeted to a certain class
      of ncRNA. Many methods rely on RNA secondary structure prediction, which is not
      always accurate and not all ncRNA classes are characterized by a common secondary
      structure. Unbiased classification methods for ncRNAs could be important to
      improve accuracy and to detect new ncRNA classes in sequencing data. RESULTS:
      Here, we present a scoring system called ALPS (alignment of pattern matrices
      score) that only uses primary information from a deep sequencing experiment, i.e.
      the relative positions and lengths of reads, to classify ncRNAs. ALPS makes no
      further assumptions, e.g. about common structural properties in the ncRNA class
      and is nevertheless able to identify ncRNA classes with high accuracy. Since ALPS
      is not designed to recognize a certain class of ncRNA, it can be used to detect
      novel ncRNA classes, as long as these unknown ncRNAs have a characteristic
      pattern of deep sequencing read lengths and positions. We evaluate our scoring
      system on publicly available deep sequencing data and show that it is able to
      classify known ncRNAs with high sensitivity and specificity. AVAILABILITY:
      Calculated pattern matrices of the datasets hESC and EB are available at the
      project web site http://www.bio.ifi.lmu.de/ALPS. An implementation of the
      described method is available upon request from the authors.

PMID- 20823304
TI  - Integrating genome assemblies with MAIA.
AB  - MOTIVATION: De novo assembly of a eukaryotic genome with next-generation
      sequencing data is still a challenging task. Over the past few years several
      assemblers have been developed, often suitable for one specific type of
      sequencing data. The number of known genomes is expanding rapidly, therefore it
      becomes possible to use multiple reference genomes for assembly projects. We
      introduce an assembly integrator that makes use of all available data, i.e.
      multiple de novo assemblies and mappings against multiple related genomes, by
      optimizing a weighted combination of criteria. RESULTS: The developed algorithm
      was applied on the de novo sequencing of the Saccharomyces cerevisiae CEN.PK 113
      7D strain. Using Solexa and 454 read data, two de novo and three comparative
      assemblies were constructed and subsequently integrated, yielding 29 contigs,
      covering more than 12 Mbp; a drastic improvement compared with the single
      assemblies. AVAILABILITY: MAIA is available as a Matlab package and can be
      downloaded from http://bioinformatics.tudelft.nl.

PMID- 20823305
TI  - Maximum likelihood estimation of locus-specific mutation rates in Y-chromosome
      short tandem repeats.
AB  - MOTIVATION: Y-chromosome short tandem repeats (Y-STRs) are widely used for
      population studies, forensic purposes and, potentially, the study of disease,
      therefore knowledge of their mutation rate is valuable. Here we show a novel
      method for estimation of site-specific Y-STR mutation rates from partial
      phylogenetic information, via the maximum likelihood framework. RESULTS: Given Y
      STR data classified into haplogroups, we de-scribe the likelihood of observed
      data, and develop optimization strategies for deriving maximum likelihood
      estimates of mutation rates. We apply our method to Y-STR data from two recent
      papers. We show that our estimates are comparable, often more accurate than those
      obtained in familial studies, although our data sample is much smaller, and was
      not collected specifically for our study. Furthermore, we obtain mutation rate
      estimates for DYS388, DYS426, DYS457, three STRs for which there were no mutation
      rate measures until now.

PMID- 20823306
TI  - Parsimony and likelihood reconstruction of human segmental duplications.
AB  - MOTIVATION: Segmental duplications > 1 kb in length with >or= 90% sequence
      identity between copies comprise nearly 5% of the human genome. They are
      frequently found in large, contiguous regions known as duplication blocks that
      can contain mosaic patterns of thousands of segmental duplications.
      Reconstructing the evolutionary history of these complex genomic regions is a non
      trivial, but important task. RESULTS: We introduce parsimony and likelihood
      techniques to analyze the evolutionary relationships between duplication blocks.
      Both techniques rely on a generic model of duplication in which long, contiguous
      substrings are copied and reinserted over large physical distances, allowing for
      a duplication block to be constructed by aggregating substrings of other blocks.
      For the likelihood method, we give an efficient dynamic programming algorithm to
      compute the weighted ensemble of all duplication scenarios that account for the
      construction of a duplication block. Using this ensemble, we derive the
      probabilities of various duplication scenarios. We formalize the task of
      reconstructing the evolutionary history of segmental duplications as an
      optimization problem on the space of directed acyclic graphs. We use a simulated
      annealing heuristic to solve the problem for a set of segmental duplications in
      the human genome in both parsimony and likelihood settings. AVAILABILITY:
      Supplementary information is available at
      http://www.cs.brown.edu/people/braphael/supplements/.

PMID- 20823307
TI  - Discriminatory power of RNA family models.
AB  - MOTIVATION: RNA family models group nucleotide sequences that share a common
      biological function. These models can be used to find new sequences belonging to
      the same family. To succeed in this task, a model needs to exhibit high
      sensitivity as well as high specificity. As model construction is guided by a
      manual process, a number of problems can occur, such as the introduction of more
      than one model for the same family or poorly constructed models. We explore the
      Rfam database to discover such problems. RESULTS: Our main contribution is in the
      definition of the discriminatory power of RNA family models, together with a
      first algorithm for its computation. In addition, we present calculations across
      the whole Rfam database that show several families lacking high specificity when
      compared to other families. We give a list of these clusters of families and
      provide a tentative explanation. Our program can be used to: (i) make sure that
      new models are not equivalent to any model already present in the database; and
      (ii) new models are not simply submodels of existing families. AVAILABILITY:
      www.tbi.univie.ac.at/software/cmcompare/. The code is licensed under the GPLv3.
      Results for the whole Rfam database and supporting scripts are available together
      with the software.

PMID- 20823308
TI  - RactIP: fast and accurate prediction of RNA-RNA interaction using integer
      programming.
AB  - MOTIVATION: Considerable attention has been focused on predicting RNA-RNA
      interaction since it is a key to identifying possible targets of non-coding small
      RNAs that regulate gene expression post-transcriptionally. A number of
      computational studies have so far been devoted to predicting joint secondary
      structures or binding sites under a specific class of interactions. In general,
      there is a trade-off between range of interaction type and efficiency of a
      prediction algorithm, and thus efficient computational methods for predicting
      comprehensive type of interaction are still awaited. RESULTS: We present RactIP,
      a fast and accurate prediction method for RNA-RNA interaction of general type
      using integer programming. RactIP can integrate approximate information on an
      ensemble of equilibrium joint structures into the objective function of integer
      programming using posterior internal and external base-paring probabilities.
      Experimental results on real interaction data show that prediction accuracy of
      RactIP is at least comparable to that of several state-of-the-art methods for RNA
      RNA interaction prediction. Moreover, we demonstrate that RactIP can run
      incomparably faster than competitive methods for predicting joint secondary
      structures. AVAILABILITY: RactIP is implemented in C++, and the source code is
      available at http://www.ncrna.org/software/ractip/.

PMID- 20823309
TI  - Solenoid and non-solenoid protein recognition using stationary wavelet packet
      transform.
AB  - MOTIVATION: Solenoid proteins are emerging as a protein class with properties
      intermediate between structured and intrinsically unstructured proteins.
      Containing repeating structural units, solenoid proteins are expected to share
      sequence similarities. However, in many cases, the sequence similarities are weak
      and non-detectable. Moreover, solenoids can be degenerated and widely vary in the
      number of units. So that it is difficult to detect them. Recently, several
      solenoid repeats detection methods have been proposed, such as self-alignment of
      the sequence, spectral analysis and discrete Fourier transform of sequence.
      Although these methods have shown good performance on certain data sets, they
      often fail to detect repeats with weak similarities. In this article, we propose
      a new approach to recognize solenoid repeats and non-solenoid proteins using
      stationary wavelet packet transform (SWPT). Our method associates with three
      advantages: (i) naturally representing five main factors of protein structure and
      properties by wavelet analysis technique; (ii) extracting novel wavelet features
      that can capture hidden components from solenoid sequence similarities and
      distinguish them from global proteins; (iii) obtaining statistics features that
      capture repeating motifs of solenoid proteins. RESULTS: Our method analyzes the
      characteristics of amino acid sequence in both spectral and temporal domains
      using SWPT. Both global and local information of proteins are captured by SWPT
      coefficients. We obtain and integrate wavelet-based features and statistics-based
      features of amino acid sequence to improve the classification task. Our proposed
      method is evaluated by comparing to state-of-the-art methods such as HHrepID and
      REPETITA. The experimental results show that our algorithm consistently
      outperforms them in areas under ROC curve. At the same false positive rate, the
      sensitivity of our WAVELET method is higher than other methods. AVAILABILITY:
      http://www.naaan.org/anvo/Software/Software.htm.

PMID- 20823310
TI  - Vorescore--fold recognition improved by rescoring of protein structure models.
AB  - SUMMARY: The identification of good protein structure models and their
      appropriate ranking is a crucial problem in structure prediction and fold
      recognition. For many alignment methods, rescoring of alignment-induced models
      using structural information can improve the separation of useful and less useful
      models as compared with the alignment score. Vorescore, a template-based protein
      structure model rescoring system is introduced. The method scores the model
      structure against the template used for the modeling using Vorolign. The method
      works on models from different alignment methods and incorporates both knowledge
      from the prediction method and the rescoring. RESULTS: The performance of
      Vorescore is evaluated in a large-scale and difficult protein structure
      prediction context. We use different threading methods to create models for 410
      targets, in three scenarios: (i) family members are contained in the template
      set; (ii) superfamily members (but no family members); and (iii) only fold
      members (but no family or superfamily members). In all cases Vorescore improves
      significantly (e.g. 40% on both Gotoh and HHalign at the fold level) on the model
      quality, and clearly outperforms the state-of-the-art physics-based model scoring
      system Rosetta. Moreover, Vorescore improves on other successful rescoring
      approaches such as Pcons and ProQ. In an additional experiment we add high
      quality models based on structural alignments to the set, which allows Vorescore
      to improve the fold recognition rate by another 50%. AVAILABILITY: All models of
      the test set (about 2 million, 44 GB gzipped) are available upon request.

PMID- 20823311
TI  - A predictor for toxin-like proteins exposes cell modulator candidates within
      viral genomes.
AB  - MOTIVATION: Animal toxins operate by binding to receptors and ion channels. These
      proteins are short and vary in sequence, structure and function. Sporadic
      discoveries have also revealed endogenous toxin-like proteins in non-venomous
      organisms. Viral proteins are the largest group of quickly evolving proteomes. We
      tested the hypothesis that toxin-like proteins exist in viruses and that they act
      to modulate functions of their hosts. RESULTS: We updated and improved a
      classifier for compact proteins resembling short animal toxins that is based on a
      machine-learning method. We applied it in a large-scale setting to identify toxin
      like proteins among short viral proteins. Among the approximately 26 000
      representatives of such short proteins, 510 sequences were positively identified.
      We focused on the 19 highest scoring proteins. Among them, we identified
      conotoxin-like proteins, growth factors receptor-like proteins and anti-bacterial
      peptides. Our predictor was shown to enhance annotation inference for many
      'uncharacterized' proteins. We conclude that our protocol can expose toxin-like
      proteins in unexplored niches including metagenomics data and enhance the
      systematic discovery of novel cell modulators for drug development. AVAILABILITY:
      ClanTox is available at http://www.clantox.cs.huji.ac.il.

PMID- 20823312
TI  - Improved sequence-based prediction of disordered regions with multilayer fusion
      of multiple information sources.
AB  - MOTIVATION: Intrinsically disordered proteins play a crucial role in numerous
      regulatory processes. Their abundance and ubiquity combined with a relatively low
      quantity of their annotations motivate research toward the development of
      computational models that predict disordered regions from protein sequences.
      Although the prediction quality of these methods continues to rise, novel and
      improved predictors are urgently needed. RESULTS: We propose a novel method,
      named MFDp (Multilayered Fusion-based Disorder predictor), that aims to improve
      over the current disorder predictors. MFDp is as an ensemble of 3 Support Vector
      Machines specialized for the prediction of short, long and generic disordered
      regions. It combines three complementary disorder predictors, sequence, sequence
      profiles, predicted secondary structure, solvent accessibility, backbone dihedral
      torsion angles, residue flexibility and B-factors. Our method utilizes a custom
      designed set of features that are based on raw predictions and aggregated raw
      values and recognizes various types of disorder. The MFDp is compared at the
      residue level on two datasets against eight recent disorder predictors and top
      performing methods from the most recent CASP8 experiment. In spite of using
      training chains with <or=25% similarity to the test sequences, our method
      consistently and significantly outperforms the other methods based on the MCC
      index. The MFDp outperforms modern disorder predictors for the binary disorder
      assignment and provides competitive real-valued predictions. The MFDp's outputs
      are also shown to outperform the other methods in the identification of proteins
      with long disordered regions. AVAILABILITY:
      http://biomine.ece.ualberta.ca/MFDp.html.

PMID- 20823313
TI  - Prototypes of elementary functional loops unravel evolutionary connections
      between protein functions.
AB  - MOTIVATION: Earlier studies of protein structure revealed closed loops with a
      characteristic size 25-30 residues and ring-like shape as a basic universal
      structural element of globular proteins. Elementary functional loops (EFLs) have
      specific signatures and provide functional residues important for
      binding/activation and principal chemical transformation steps of the enzymatic
      reaction. The goal of this work is to show how these functional loops evolved
      from pre-domain peptides and to find a set of prototypes from which the EFLs of
      contemporary proteins originated. RESULTS: This article describes a computational
      method for deriving prototypes of EFLs based on the sequences of complete
      genomes. The procedure comprises the iterative derivation of sequence profiles
      followed by their hierarchical clustering. The scoring function takes into
      account information content on profile positions, thus preserving the signature.
      The statistical significance of scores is evaluated from the empirical
      distribution of scores of the background model. A set of prototypes of EFLs from
      archaeal proteomes is derived. This set delineates evolutionary connections
      between major functions and illuminates how folds and functions emerged in pre
      domain evolution as a combination of prototypes.

PMID- 20823314
TI  - A varying threshold method for ChIP peak-calling using multiple sources of
      information.
AB  - MOTIVATION: Gene regulation commonly involves interaction among DNA, proteins and
      biochemical conditions. Using chromatin immunoprecipitation (ChIP) technologies,
      protein-DNA interactions are routinely detected in the genome scale.
      Computational methods that detect weak protein-binding signals and simultaneously
      maintain a high specificity yet remain to be challenging. An attractive approach
      is to incorporate biologically relevant data, such as protein co-occupancy, to
      improve the power of protein-binding detection. We call the additional data
      related with the target protein binding as supporting tracks. RESULTS: We propose
      a novel but rigorous statistical method to identify protein occupancy in ChIP
      data using multiple supporting tracks (PASS2). We demonstrate that utilizing
      biologically related information can significantly increase the discovery of true
      protein-binding sites, while still maintaining a desired level of false positive
      calls. Applying the method to GATA1 restoration in mouse erythroid cell line, we
      detected many new GATA1-binding sites using GATA1 co-occupancy data.
      AVAILABILITY: http://stat.psu.edu/ approximately yuzhang/pass2.tar.

PMID- 20823315
TI  - De-correlating expression in gene-set analysis.
AB  - MOTIVATION: Group-wise pattern analysis of genes, known as gene-set analysis
      (GSA), addresses the differential expression pattern of biologically pre-defined
      gene sets. GSA exhibits high statistical power and has revealed many novel
      biological processes associated with specific phenotypes. In most cases, however,
      GSA relies on the invalid assumption that the members of each gene set are
      sampled independently, which increases false predictions. RESULTS: We propose an
      algorithm, termed DECO, to remove (or alleviate) the bias caused by the
      correlation of the expression data in GSAs. This is accomplished through the
      eigenvalue-decomposition of covariance matrixes and a series of linear
      transformations of data. In particular, moderate de-correlation methods that
      truncate or re-scale eigenvalues were proposed for a more reliable analysis.
      Tests of simulated and real experimental data show that DECO effectively corrects
      the correlation structure of gene expression and improves the prediction accuracy
      (specificity and sensitivity) for both gene- and sample-randomizing GSA methods.
      AVAILABILITY: The MATLAB codes and the tested data sets are available at
      ftp://deco.nims.re.kr/pub or from the author.

PMID- 20823316
TI  - Discovering graphical Granger causality using the truncating lasso penalty.
AB  - MOTIVATION: Components of biological systems interact with each other in order to
      carry out vital cell functions. Such information can be used to improve
      estimation and inference, and to obtain better insights into the underlying
      cellular mechanisms. Discovering regulatory interactions among genes is therefore
      an important problem in systems biology. Whole-genome expression data over time
      provides an opportunity to determine how the expression levels of genes are
      affected by changes in transcription levels of other genes, and can therefore be
      used to discover regulatory interactions among genes. RESULTS: In this article,
      we propose a novel penalization method, called truncating lasso, for estimation
      of causal relationships from time-course gene expression data. The proposed
      penalty can correctly determine the order of the underlying time series, and
      improves the performance of the lasso-type estimators. Moreover, the resulting
      estimate provides information on the time lag between activation of transcription
      factors and their effects on regulated genes. We provide an efficient algorithm
      for estimation of model parameters, and show that the proposed method can
      consistently discover causal relationships in the large p, small n setting. The
      performance of the proposed model is evaluated favorably in simulated, as well as
      real, data examples. AVAILABILITY: The proposed truncating lasso method is
      implemented in the R-package 'grangerTlasso' and is freely available at
      http://www.stat.lsa.umich.edu/~shojaie/.

PMID- 20823317
TI  - is-rSNP: a novel technique for in silico regulatory SNP detection.
AB  - MOTIVATION: Determining the functional impact of non-coding disease-associated
      single nucleotide polymorphisms (SNPs) identified by genome-wide association
      studies (GWAS) is challenging. Many of these SNPs are likely to be regulatory
      SNPs (rSNPs): variations which affect the ability of a transcription factor (TF)
      to bind to DNA. However, experimental procedures for identifying rSNPs are
      expensive and labour intensive. Therefore, in silico methods are required for
      rSNP prediction. By scoring two alleles with a TF position weight matrix (PWM),
      it can be determined which SNPs are likely rSNPs. However, predictions in this
      manner are noisy and no method exists that determines the statistical
      significance of a nucleotide variation on a PWM score. RESULTS: We have designed
      an algorithm for in silico rSNP detection called is-rSNP. We employ novel
      convolution methods to determine the complete distributions of PWM scores and
      ratios between allele scores, facilitating assignment of statistical significance
      to rSNP effects. We have tested our method on 41 experimentally verified rSNPs,
      correctly predicting the disrupted TF in 28 cases. We also analysed 146 disease
      associated SNPs with no known functional impact in an attempt to identify
      candidate rSNPs. Of the 11 significantly predicted disrupted TFs, 9 had previous
      evidence of being associated with the disease in the literature. These results
      demonstrate that is-rSNP is suitable for high-throughput screening of SNPs for
      potential regulatory function. This is a useful and important tool in the
      interpretation of GWAS. AVAILABILITY: is-rSNP software is available for use at:
      www.genomics.csse.unimelb.edu.au/is-rSNP.

PMID- 20823318
TI  - Nonlinear dimension reduction and clustering by Minimum Curvilinearity unfold
      neuropathic pain and tissue embryological classes.
AB  - MOTIVATION: Nonlinear small datasets, which are characterized by low numbers of
      samples and very high numbers of measures, occur frequently in computational
      biology, and pose problems in their investigation. Unsupervised hybrid-two-phase
      (H2P) procedures-specifically dimension reduction (DR), coupled with clustering
      provide valuable assistance, not only for unsupervised data classification, but
      also for visualization of the patterns hidden in high-dimensional feature space.
      METHODS: 'Minimum Curvilinearity' (MC) is a principle that-for small datasets
      suggests the approximation of curvilinear sample distances in the feature space
      by pair-wise distances over their minimum spanning tree (MST), and thus avoids
      the introduction of any tuning parameter. MC is used to design two novel forms of
      nonlinear machine learning (NML): Minimum Curvilinear embedding (MCE) for DR, and
      Minimum Curvilinear affinity propagation (MCAP) for clustering. RESULTS: Compared
      with several other unsupervised and supervised algorithms, MCE and MCAP, whether
      individually or combined in H2P, overcome the limits of classical approaches.
      High performance was attained in the visualization and classification of: (i)
      pain patients (proteomic measurements) in peripheral neuropathy; (ii) human organ
      tissues (genomic transcription factor measurements) on the basis of their
      embryological origin. CONCLUSION: MC provides a valuable framework to estimate
      nonlinear distances in small datasets. Its extension to large datasets is
      prefigured for novel NMLs. Classification of neuropathic pain by proteomic
      profiles offers new insights for future molecular and systems biology
      characterization of pain. Improvements in tissue embryological classification
      refine results obtained in an earlier study, and suggest a possible
      reinterpretation of skin attribution as mesodermal. AVAILABILITY:
      https://sites.google.com/site/carlovittoriocannistraci/home.

PMID- 20823319
TI  - BioXSD: the common data-exchange format for everyday bioinformatics web services.
AB  - MOTIVATION: The world-wide community of life scientists has access to a large
      number of public bioinformatics databases and tools, which are developed and
      deployed using diverse technologies and designs. More and more of the resources
      offer programmatic web-service interface. However, efficient use of the resources
      is hampered by the lack of widely used, standard data-exchange formats for the
      basic, everyday bioinformatics data types. RESULTS: BioXSD has been developed as
      a candidate for standard, canonical exchange format for basic bioinformatics
      data. BioXSD is represented by a dedicated XML Schema and defines syntax for
      biological sequences, sequence annotations, alignments and references to
      resources. We have adapted a set of web services to use BioXSD as the input and
      output format, and implemented a test-case workflow. This demonstrates that the
      approach is feasible and provides smooth interoperability. Semantics for BioXSD
      is provided by annotation with the EDAM ontology. We discuss in a separate
      section how BioXSD relates to other initiatives and approaches, including
      existing standards and the Semantic Web. AVAILABILITY: The BioXSD 1.0 XML Schema
      is freely available at http://www.bioxsd.org/BioXSD-1.0.xsd under the Creative
      Commons BY-ND 3.0 license. The http://bioxsd.org web page offers documentation,
      examples of data in BioXSD format, example workflows with source codes in common
      programming languages, an updated list of compatible web services and tools and a
      repository of feature requests from the community.

PMID- 20823320
TI  - Discovering drug-drug interactions: a text-mining and reasoning approach based on
      properties of drug metabolism.
AB  - MOTIVATION: Identifying drug-drug interactions (DDIs) is a critical process in
      drug administration and drug development. Clinical support tools often provide
      comprehensive lists of DDIs, but they usually lack the supporting scientific
      evidences and different tools can return inconsistent results. In this article,
      we propose a novel approach that integrates text mining and automated reasoning
      to derive DDIs. Through the extraction of various facts of drug metabolism, not
      only the DDIs that are explicitly mentioned in text can be extracted but also the
      potential interactions that can be inferred by reasoning. RESULTS: Our approach
      was able to find several potential DDIs that are not present in DrugBank. We
      manually evaluated these interactions based on their supporting evidences, and
      our analysis revealed that 81.3% of these interactions are determined to be
      correct. This suggests that our approach can uncover potential DDIs with
      scientific evidences explaining the mechanism of the interactions.

PMID- 20823321
TI  - Discriminative and informative features for biomolecular text mining with
      ensemble feature selection.
AB  - MOTIVATION: In the field of biomolecular text mining, black box behavior of
      machine learning systems currently limits understanding of the true nature of the
      predictions. However, feature selection (FS) is capable of identifying the most
      relevant features in any supervised learning setting, providing insight into the
      specific properties of the classification algorithm. This allows us to build more
      accurate classifiers while at the same time bridging the gap between the black
      box behavior and the end-user who has to interpret the results. RESULTS: We show
      that our FS methodology successfully discards a large fraction of machine
      generated features, improving classification performance of state-of-the-art text
      mining algorithms. Furthermore, we illustrate how FS can be applied to gain
      understanding in the predictions of a framework for biomolecular event extraction
      from text. We include numerous examples of highly discriminative features that
      model either biological reality or common linguistic constructs. Finally, we
      discuss a number of insights from our FS analyses that will provide the
      opportunity to considerably improve upon current text mining tools. AVAILABILITY:
      The FS algorithms and classifiers are available in Java-ML (http://java
      ml.sf.net). The datasets are publicly available from the BioNLP'09 Shared Task
      web site (http://www-tsujii.is.s.u-tokyo.ac.jp/GENIA/SharedTask/).

PMID- 20823322
TI  - Improving disease gene prioritization using the semantic similarity of Gene
      Ontology terms.
AB  - MOTIVATION: Many hereditary human diseases are polygenic, resulting from sequence
      alterations in multiple genes. Genomic linkage and association studies are
      commonly performed for identifying disease-related genes. Such studies often
      yield lists of up to several hundred candidate genes, which have to be
      prioritized and validated further. Recent studies discovered that genes involved
      in phenotypically similar diseases are often functionally related on the
      molecular level. RESULTS: Here, we introduce MedSim, a novel approach for ranking
      candidate genes for a particular disease based on functional comparisons
      involving the Gene Ontology. MedSim uses functional annotations of known disease
      genes for assessing the similarity of diseases as well as the disease relevance
      of candidate genes. We benchmarked our approach with genes known to be involved
      in 99 diseases taken from the OMIM database. Using artificial quantitative trait
      loci, MedSim achieved excellent performance with an area under the ROC curve of
      up to 0.90 and a sensitivity of over 70% at 90% specificity when classifying gene
      products according to their disease relatedness. This performance is comparable
      or even superior to related methods in the field, albeit using less and thus more
      easily accessible information. AVAILABILITY: MedSim is offered as part of our
      FunSimMat web service (http://www.funsimmat.de).

PMID- 20823323
TI  - Utopia documents: linking scholarly literature with research data.
AB  - MOTIVATION: In recent years, the gulf between the mass of accumulating-research
      data and the massive literature describing and analyzing those data has widened.
      The need for intelligent tools to bridge this gap, to rescue the knowledge being
      systematically isolated in literature and data silos, is now widely acknowledged.
      RESULTS: To this end, we have developed Utopia Documents, a novel PDF reader that
      semantically integrates visualization and data-analysis tools with published
      research articles. In a successful pilot with editors of the Biochemical Journal
      (BJ), the system has been used to transform static document features into objects
      that can be linked, annotated, visualized and analyzed interactively
      (http://www.biochemj.org/bj/424/3/). Utopia Documents is now used routinely by BJ
      editors to mark up article content prior to publication. Recent additions include
      integration of various text-mining and biodatabase plugins, demonstrating the
      system's ability to seamlessly integrate on-line content with PDF articles.
      AVAILABILITY: http://getutopia.com.

PMID- 20823324
TI  - A graphical method for reducing and relating models in systems biology.
AB  - MOTIVATION: In Systems Biology, an increasing collection of models of various
      biological processes is currently developed and made available in publicly
      accessible repositories, such as biomodels.net for instance, through common
      exchange formats such as SBML. To date, however, there is no general method to
      relate different models to each other by abstraction or reduction relationships,
      and this task is left to the modeler for re-using and coupling models. In
      mathematical biology, model reduction techniques have been studied for a long
      time, mainly in the case where a model exhibits different time scales, or
      different spatial phases, which can be analyzed separately. These techniques are
      however far too restrictive to be applied on a large scale in systems biology,
      and do not take into account abstractions other than time or phase
      decompositions. Our purpose here is to propose a general computational method for
      relating models together, by considering primarily the structure of the
      interactions and abstracting from their dynamics in a first step. RESULTS: We
      present a graph-theoretic formalism with node merge and delete operations, in
      which model reductions can be studied as graph matching problems. From this
      setting, we derive an algorithm for deciding whether there exists a reduction
      from one model to another, and evaluate it on the computation of the reduction
      relations between all SBML models of the biomodels.net repository. In particular,
      in the case of the numerous models of MAPK signalling, and of the circadian
      clock, biologically meaningful mappings between models of each class are
      automatically inferred from the structure of the interactions. We conclude on the
      generality of our graphical method, on its limits with respect to the
      representation of the structure of the interactions in SBML, and on some
      perspectives for dealing with the dynamics. AVAILABILITY: The algorithms
      described in this article are implemented in the open-source software modeling
      platform BIOCHAM available at http://contraintes.inria.fr/biocham The models used
      in the experiments are available from http://www.biomodels.net/.

PMID- 20823325
TI  - A novel approach for determining environment-specific protein costs: the case of
      Arabidopsis thaliana.
AB  - MOTIVATION: Comprehensive understanding of cellular processes requires
      development of approaches which consider the energetic balances in the cell. The
      existing approaches that address this problem are based on defining energy
      equivalent costs which do not include the effects of a changing environment. By
      incorporating these effects, one could provide a framework for integrating
      'omics' data from various levels of the system in order to provide
      interpretations with respect to the energy state and to elicit conclusions about
      putative global energy-related response mechanisms in the cell. RESULTS: Here we
      define a cost measure for amino acid synthesis based on flux balance analysis of
      a genome-scale metabolic network, and develop methods for its integration with
      proteomics and metabolomics data. This is a first measure which accounts for the
      effect of different environmental conditions. We applied this approach to a
      genome-scale network of Arabidopsis thaliana and calculated the costs for all
      amino acids and proteins present in the network under light and dark conditions.
      Integration of function and process ontology terms in the analysis of protein
      abundances and their costs indicates that, during the night, the cell favors
      cheaper proteins compared with the light environment. However, this does not
      imply that there is squandering of resources during the day. The results from the
      association analysis between the costs, levels and well-defined expenses of amino
      acid synthesis, indicate that our approach not only captures the adjustment made
      at the switch of conditions, but also could explain the anticipation of resource
      usage via a global energy-related regulatory mechanism of amino acid and protein
      synthesis.

PMID- 20823326
TI  - Bayesian experts in exploring reaction kinetics of transcription circuits.
AB  - MOTIVATION: Biochemical reactions in cells are made of several types of
      biological circuits. In current systems biology, making differential equation
      (DE) models simulatable in silico has been an appealing, general approach to
      uncover a complex world of biochemical reaction dynamics. Despite of a need for
      simulation-aided studies, our research field has yet provided no clear answers:
      how to specify kinetic values in models that are difficult to measure from
      experimental/theoretical analyses on biochemical kinetics. RESULTS: We present a
      novel non-parametric Bayesian approach to this problem. The key idea lies in the
      development of a Dirichlet process (DP) prior distribution, called Bayesian
      experts, which reflects substantive knowledge on reaction mechanisms inherent in
      given models and experimentally observable kinetic evidences to the subsequent
      parameter search. The DP prior identifies significant local regions of unknown
      parameter space before proceeding to the posterior analyses. This article reports
      that a Bayesian expert-inducing stochastic search can effectively explore unknown
      parameters of in silico transcription circuits such that solutions of DEs
      reproduce transcriptomic time course profiles. AVAILABILITY: A sample source code
      is available at the URL http://daweb.ism.ac.jp/~yoshidar/lisdas/.

PMID- 20823327
TI  - Dynamic deterministic effects propagation networks: learning signalling pathways
      from longitudinal protein array data.
AB  - MOTIVATION: Network modelling in systems biology has become an important tool to
      study molecular interactions in cancer research, because understanding the
      interplay of proteins is necessary for developing novel drugs and therapies. De
      novo reconstruction of signalling pathways from data allows to unravel
      interactions between proteins and make qualitative statements on possible
      aberrations of the cellular regulatory program. We present a new method for
      reconstructing signalling networks from time course experiments after external
      perturbation and show an application of the method to data measuring abundance of
      phosphorylated proteins in a human breast cancer cell line, generated on reverse
      phase protein arrays. RESULTS: Signalling dynamics is modelled using active and
      passive states for each protein at each timepoint. A fixed signal propagation
      scheme generates a set of possible state transitions on a discrete timescale for
      a given network hypothesis, reducing the number of theoretically reachable
      states. A likelihood score is proposed, describing the probability of
      measurements given the states of the proteins over time. The optimal sequence of
      state transitions is found via a hidden Markov model and network structure search
      is performed using a genetic algorithm that optimizes the overall likelihood of a
      population of candidate networks. Our method shows increased performance compared
      with two different dynamical Bayesian network approaches. For our real data, we
      were able to find several known signalling cascades from the ERBB signalling
      pathway. AVAILABILITY: Dynamic deterministic effects propagation networks is
      implemented in the R programming language and available at
      http://www.dkfz.de/mga2/ddepn/.

PMID- 20823328
TI  - Efficient parameter search for qualitative models of regulatory networks using
      symbolic model checking.
AB  - MOTIVATION: Investigating the relation between the structure and behavior of
      complex biological networks often involves posing the question if the
      hypothesized structure of a regulatory network is consistent with the observed
      behavior, or if a proposed structure can generate a desired behavior. RESULTS:
      The above questions can be cast into a parameter search problem for qualitative
      models of regulatory networks. We develop a method based on symbolic model
      checking that avoids enumerating all possible parametrizations, and show that
      this method performs well on real biological problems, using the IRMA synthetic
      network and benchmark datasets. We test the consistency between IRMA and time
      series expression profiles, and search for parameter modifications that would
      make the external control of the system behavior more robust. AVAILABILITY: GNA
      and the IRMA model are available at http://ibis.inrialpes.fr/.

PMID- 20823329
TI  - How threshold behaviour affects the use of subgraphs for network comparison.
AB  - MOTIVATION: A wealth of protein-protein interaction (PPI) data has recently
      become available. These data are organized as PPI networks and an efficient and
      biologically meaningful method to compare such PPI networks is needed. As a first
      step, we would like to compare observed networks to established network models,
      under the aspect of small subgraph counts, as these are conjectured to relate to
      functional modules in the PPI network. We employ the software tool GraphCrunch
      with the Graphlet Degree Distribution Agreement (GDDA) score to examine the use
      of such counts for network comparison. RESULTS: Our results show that the GDDA
      score has a pronounced dependency on the number of edges and vertices of the
      networks being considered. This should be taken into account when testing the fit
      of models. We provide a method for assessing the statistical significance of the
      fit between random graph models and biological networks based on non-parametric
      tests. Using this method we examine the fit of Erdos-Renyi (ER), ER with fixed
      degree distribution and geometric (3D) models to PPI networks. Under these
      rigorous tests none of these models fit to the PPI networks. The GDDA score is
      not stable in the region of graph density relevant to current PPI networks. We
      hypothesize that this score instability is due to the networks under
      consideration having a graph density in the threshold region for the appearance
      of small subgraphs. This is true for both geometric (3D) and ER random graph
      models. Such threshold behaviour may be linked to the robustness and efficiency
      properties of the PPI networks.

PMID- 20823330
TI  - Candidate gene prioritization based on spatially mapped gene expression: an
      application to XLMR.
AB  - MOTIVATION: The identification of genes involved in specific phenotypes, such as
      human hereditary diseases, often requires the time-consuming and expensive
      examination of a large number of positional candidates selected by genome-wide
      techniques such as linkage analysis and association studies. Even considering the
      positive impact of next-generation sequencing technologies, the prioritization of
      these positional candidates may be an important step for disease-gene
      identification. RESULTS: Here, we report a large-scale analysis of spatial, i.e.
      3D, gene-expression data from an entire organ (the mouse brain) for the purpose
      of evaluating and ranking positional candidate genes, showing that the spatial
      gene-expression patterns can be successfully exploited for the prediction of gene
      phenotype associations not only for mouse phenotypes, but also for human central
      nervous system-related Mendelian disorders. We apply our method to the case of X
      linked mental retardation, compare the predictions to the results obtained from a
      previous large-scale resequencing study of chromosome X and discuss some
      promising novel candidates.

PMID- 20823331
TI  - Inferring cancer subnetwork markers using density-constrained biclustering.
AB  - MOTIVATION: Recent genomic studies have confirmed that cancer is of utmost
      phenotypical complexity, varying greatly in terms of subtypes and evolutionary
      stages. When classifying cancer tissue samples, subnetwork marker approaches have
      proven to be superior over single gene marker approaches, most importantly in
      cross-platform evaluation schemes. However, prior subnetwork-based approaches do
      not explicitly address the great phenotypical complexity of cancer. RESULTS: We
      explicitly address this and employ density-constrained biclustering to compute
      subnetwork markers, which reflect pathways being dysregulated in many, but not
      necessarily all samples under consideration. In breast cancer we achieve
      substantial improvements over all cross-platform applicable approaches when
      predicting TP53 mutation status in a well-established non-cross-platform setting.
      In colon cancer, we raise prediction accuracy in the most difficult instances
      from 87% to 93% for cancer versus non-cancer and from 83% to (astonishing) 92%,
      for with versus without liver metastasis, in well-established cross-platform
      evaluation schemes. AVAILABILITY: Software is available on request.

PMID- 20823332
TI  - Modeling associations between genetic markers using Bayesian networks.
AB  - MOTIVATION: Understanding the patterns of association between polymorphisms at
      different loci in a population (linkage disequilibrium, LD) is of fundamental
      importance in various genetic studies. Many coefficients were proposed for
      measuring the degree of LD, but they provide only a static view of the current LD
      structure. Generative models (GMs) were proposed to go beyond these measures,
      giving not only a description of the actual LD structure but also a tool to help
      understanding the process that generated such structure. GMs based in coalescent
      theory have been the most appealing because they link LD to evolutionary factors.
      Nevertheless, the inference and parameter estimation of such models is still
      computationally challenging. RESULTS: We present a more practical method to build
      GM that describe LD. The method is based on learning weighted Bayesian network
      structures from haplotype data, extracting equivalence structure classes and
      using them to model LD. The results obtained in public data from the HapMap
      database showed that the method is a promising tool for modeling LD. The
      associations represented by the learned models are correlated with the
      traditional measure of LD D'. The method was able to represent LD blocks found by
      standard tools. The granularity of the association blocks and the readability of
      the models can be controlled in the method. The results suggest that the
      causality information gained by our method can be useful to tell about the
      conservability of the genetic markers and to guide the selection of subset of
      representative markers. AVAILABILITY: The implementation of the method is
      available upon request by email.

PMID- 20823333
TI  - Prediction of a gene regulatory network linked to prostate cancer from gene
      expression, microRNA and clinical data.
AB  - MOTIVATION: Cancer is a complex disease, triggered by mutations in multiple genes
      and pathways. There is a growing interest in the application of systems biology
      approaches to analyze various types of cancer-related data to understand the
      overwhelming complexity of changes induced by the disease. RESULTS: We
      reconstructed a regulatory module network using gene expression, microRNA
      expression and a clinical parameter, all measured in lymphoblastoid cell lines
      derived from patients having aggressive or non-aggressive forms of prostate
      cancer. Our analysis identified several modules enriched in cell cycle-related
      genes as well as novel functional categories that might be linked to prostate
      cancer. Almost one-third of the regulators predicted to control the expression
      levels of the modules are microRNAs. Several of them have already been
      characterized as causal in various diseases, including cancer. We also predicted
      novel microRNAs that have never been associated to this type of tumor.
      Furthermore, the condition-dependent expression of several modules could be
      linked to the value of a clinical parameter characterizing the aggressiveness of
      the prostate cancer. Taken together, our results help to shed light on the
      consequences of aggressive and non-aggressive forms of prostate cancer.
      AVAILABILITY: The complete regulatory network is available as an interactive
      supplementary web site at the following URL:
      http://bioinformatics.psb.ugent.be/webtools/pronet/.

PMID- 20823334
TI  - Semi-supervised multi-task learning for predicting interactions between HIV-1 and
      human proteins.
AB  - MOTIVATION: Protein-protein interactions (PPIs) are critical for virtually every
      biological function. Recently, researchers suggested to use supervised learning
      for the task of classifying pairs of proteins as interacting or not. However, its
      performance is largely restricted by the availability of truly interacting
      proteins (labeled). Meanwhile, there exists a considerable amount of protein
      pairs where an association appears between two partners, but not enough
      experimental evidence to support it as a direct interaction (partially labeled).
      RESULTS: We propose a semi-supervised multi-task framework for predicting PPIs
      from not only labeled, but also partially labeled reference sets. The basic idea
      is to perform multi-task learning on a supervised classification task and a semi
      supervised auxiliary task. The supervised classifier trains a multi-layer
      perceptron network for PPI predictions from labeled examples. The semi-supervised
      auxiliary task shares network layers of the supervised classifier and trains with
      partially labeled examples. Semi-supervision could be utilized in multiple ways.
      We tried three approaches in this article, (i) classification (to distinguish
      partial positives with negatives); (ii) ranking (to rate partial positive more
      likely than negatives); (iii) embedding (to make data clusters get similar
      labels). We applied this framework to improve the identification of interacting
      pairs between HIV-1 and human proteins. Our method improved upon the state-of-the
      art method for this task indicating the benefits of semi-supervised multi-task
      learning using auxiliary information. AVAILABILITY:
      http://www.cs.cmu.edu/~qyj/HIVsemi.

PMID- 20823335
TI  - Detecting host factors involved in virus infection by observing the clustering of
      infected cells in siRNA screening images.
AB  - MOTIVATION: Detecting human proteins that are involved in virus entry and
      replication is facilitated by modern high-throughput RNAi screening technology.
      However, hit lists from different laboratories have shown only little
      consistency. This may be caused by not only experimental discrepancies, but also
      not fully explored possibilities of the data analysis. We wanted to improve
      reliability of such screens by combining a population analysis of infected cells
      with an established dye intensity readout. RESULTS: Viral infection is mainly
      spread by cell-cell contacts and clustering of infected cells can be observed
      during spreading of the infection in situ and in vivo. We employed this
      clustering feature to define knockdowns which harm viral infection efficiency of
      human Hepatitis C Virus. Images of knocked down cells for 719 human kinase genes
      were analyzed with an established point pattern analysis method (Ripley's K
      function) to detect knockdowns in which virally infected cells did not show any
      clustering and therefore were hindered to spread their infection to their
      neighboring cells. The results were compared with a statistical analysis using a
      common intensity readout of the GFP-expressing viruses and a luciferase-based
      secondary screen yielding five promising host factors which may suit as potential
      targets for drug therapy. CONCLUSION: We report of an alternative method for high
      throughput imaging methods to detect host factors being relevant for the
      infection efficiency of viruses. The method is generic and has the potential to
      be used for a large variety of different viruses and treatments being screened by
      imaging techniques.

PMID- 20823336
TI  - Mass spectrometry data processing using zero-crossing lines in multi-scale of
      Gaussian derivative wavelet.
AB  - MOTIVATION: Peaks are the key information in mass spectrometry (MS) which has
      been increasingly used to discover diseases-related proteomic patterns. Peak
      detection is an essential step for MS-based proteomic data analysis. Recently,
      several peak detection algorithms have been proposed. However, in these
      algorithms, there are three major deficiencies: (i) because the noise is often
      removed, the true signal could also be removed; (ii) baseline removal step may
      get rid of true peaks and create new false peaks; (iii) in peak quantification
      step, a threshold of signal-to-noise ratio (SNR) is usually used to remove false
      peaks; however, noise estimations in SNR calculation are often inaccurate in
      either time or wavelet domain. In this article, we propose new algorithms to
      solve these problems. First, we use bivariate shrinkage estimator in stationary
      wavelet domain to avoid removing true peaks in denoising step. Second, without
      baseline removal, zero-crossing lines in multi-scale of derivative Gaussian
      wavelets are investigated with mixture of Gaussian to estimate discriminative
      parameters of peaks. Third, in quantification step, the frequency, SD, height and
      rank of peaks are used to detect both high and small energy peaks with robustness
      to noise. RESULTS: We propose a novel Gaussian Derivative Wavelet (GDWavelet)
      method to more accurately detect true peaks with a lower false discovery rate
      than existing methods. The proposed GDWavelet method has been performed on the
      real Surface-Enhanced Laser Desorption/Ionization Time-Of-Flight (SELDI-TOF)
      spectrum with known polypeptide positions and on two synthetic data with Gaussian
      and real noise. All experimental results demonstrate that our method outperforms
      other commonly used methods. The standard receiver operating characteristic (ROC)
      curves are used to evaluate the experimental results. AVAILABILITY:
      http://ranger.uta.edu/~heng/MS/GDWavelet.html or
      http://www.naaan.org/nhanguyen/archive.htm.

PMID- 20823338
TI  - Genetic and epigenetic dynamics of a retrotransposon after allopolyploidization
      of wheat.
AB  - Allopolyploidy, or the combination of two or more distinct genomes in one
      nucleus, is usually accompanied by radical genomic changes involving transposable
      elements (TEs). The dynamics of TEs after an allopolyploidization event are
      poorly understood. In this study, we analyzed the methylation state and genetic
      rearrangements of a high copied, newly amplified terminal-repeat retrotransposon
      in miniature (TRIM) family in wheat termed Veju. We found that Veju insertion
      sites underwent massive methylation changes in the first four generations of a
      newly formed wheat allohexaploid. Hypomethylation or hypermethylation occurred in
      ~43% of the tested insertion sites; while hypomethylation was significantly
      predominant in the first three generations of the newly formed allohexaploid,
      hypermethylation became predominant in the subsequent generation. In addition, we
      determined that the methylation state of Veju long terminal repeats (LTRs) might
      be correlated with the deletion and/or insertion of the TE. While most of the
      methylation changes and deletions of Veju occurred in the first generation of the
      newly formed allohexaploid, most Veju insertions were seen in the second
      generation. Finally, using quantitative PCR, we quantitatively assessed the
      genome composition of Veju in the newly formed allohexaploid and found that up to
      50% of Veju LTRs were deleted in the first generation. Retrotransposition bursts
      in subsequent generations, however, led to increases in Veju elements. In light
      of these findings, the underlying mechanisms of TRIM rearrangements are
      discussed.

PMID- 20823339
TI  - Insights into species divergence and the evolution of hermaphroditism from
      fertile interspecies hybrids of Caenorhabditis nematodes.
AB  - The architecture of both phenotypic variation and reproductive isolation are
      important problems in evolutionary genetics. The nematode genus Caenorhabditis
      includes both gonochoristic (male/female) and androdioecious (male/hermaprodite)
      species. However, the natural genetic variants distinguishing reproductive mode
      remain unknown, and nothing is known about the genetic basis of postzygotic
      isolation in the genus. Here we describe the hybrid genetics of the first
      Caenorhabditis species pair capable of producing fertile hybrid progeny, the
      gonochoristic Caenorhabditis sp. 9 and the androdioecious C. briggsae. Though
      many interspecies F(1) arrest during embryogenesis, a viable subset develops into
      fertile females and sterile males. Reciprocal parental crosses reveal asymmetry
      in male-specific viability, female fertility, and backcross viability. Selfing
      and spermatogenesis are extremely rare in XX F(1), and almost all hybrid self
      progeny are inviable. Consistent with this, F(1) females do not express male
      specific molecular germline markers. We also investigated three approaches to
      producing hybrid hermaphrodites. A dominant mutagenesis screen for self-fertile
      F(1) hybrids was unsuccessful. Polyploid F(1) hybrids with increased C. briggsae
      genomic material did show elevated rates of selfing, but selfed progeny were
      mostly inviable. Finally, the use of backcrosses to render the hybrid genome
      partial homozygous for C. briggsae alleles did not increase the incidence of
      selfing or spermatogenesis relative to the F(1) generation. These hybrid animals
      were genotyped at 23 loci, and significant segregation distortion (biased against
      C. briggsae) was detected at 13 loci. This, combined with an absence of
      productive hybrid selfing, prevents formulation of simple hypotheses about the
      genetic architecture of hermaphroditism. In the near future, this hybrid system
      will likely be fruitful for understanding the genetics of reproductive isolation
      in Caenorhabditis.

PMID- 20823340
TI  - Tissue culture-induced novel epialleles of a Myb transcription factor encoded by
      pericarp color1 in maize.
AB  - Plants regenerated from tissue culture often display somaclonal variation, that
      is, somatic and often meiotically heritable phenotypic variation that can result
      from both genetic and epigenetic modifications. To better understand the
      molecular basis of somaclonal variation, we have characterized four unique tissue
      culture-derived epialleles of the pericarp color1 (p1) gene of maize (Zea mays
      L.). The progenitor p1 allele, P1-wr, is composed of multiple head-to-tail
      tandemly arranged copies of the complete gene unit and specifies brick-red
      phlobaphene pigmentation in the cob glumes. The novel epialleles identified in
      progeny plants regenerated from tissue culture showed partial to complete loss of
      p1 function indicated by pink or colorless cob glumes. Loss of pigmentation was
      correlated with nearly complete loss of p1 steady-state transcripts. DNA gel-blot
      analysis and genomic bisulfite sequencing showed that silencing of the epialleles
      was associated with hypermethylation of a region in the second intron of P1-wr.
      Presence of Unstable factor for orange1 (Ufo1), an unlinked epigenetic modifier
      of p1, restored the cob glume pigmentation in the silenced alleles, and such
      reactivation was accompanied by hypomethylation of the p1 sequence. This
      observation confirmed that silencing of the epialleles is indeed due to
      epigenetic modifications and that the p1 epialleles were capable of functioning
      in the presence of the correct trans-acting factors. While the low-copy regions
      of the genome generally undergo hypomethylation during tissue culture, our study
      shows that the tandemly repeated genes are also prone to hypermethylation and
      epigenetic silencing.

PMID- 20823341
TI  - Signaling events leading to red-light-induced suppression of photomorphogenesis
      in wheat (Triticum aestivum).
AB  - Perception of red light (400 MUmol photon m2/s) by the shoot bottom turned off
      the greening process in wheat. To understand the signaling cascade leading to
      this photomorphogenic response, certain signaling components were probed in
      seedlings grown in different light regimes. Upon analysis the gene expression of
      heterotrimeric Galpha and Gbeta were severely down-regulated in seedlings grown
      without vermiculite and having their shoot bottom exposed to red light (R/V-) and
      was similar to that of dark-grown seedlings. Supplementing the red-light-grown V-
      seedlings with blue light resulted in up-regulation of both Galpha and Gbeta
      expression, suggesting that blue light is able to modulate G protein expression.
      Treatment of cytokinin analog benzyladenine to cytokinin-deficient red-light
      grown R/V- seedlings resulted in up-regulation of gene expression of both Galpha
      and Gbeta. To probe further, modulators of signal transduction pathway--AlF3 (G
      protein activator), LaCl3 (Ca(2+) channel blocker), NaF (nonspecific phosphatase
      inhibitor), or calmodulin (CaM) antagonists trifluoperazine (TFP) and N-(6
      aminohexyl)-5-chloro-1-nafthalene-sulfonamide (W-7)--were added along with
      Hoagland solution to the roots of 4-day-old etiolated seedlings, grown on
      germination paper and transferred to red light. AlF3, LaCl3, NaF failed to elicit
      any photomorphogenic response. However, CaM antagonists TFP and W-7 significantly
      reversed the red-light-induced suppression of photomorphogenesis. Phosphorylation
      of proteins assayed in the absence or presence of CaM antagonist TFP revealed
      respective up-regulation or down-regulation of phosphorylation of several
      plastidic proteins in R/V- seedlings. These suggest that signal transduction of
      red light perceived by the shoot bottom to suppress photomorphogenesis is
      mediated by CaM-dependent protein kinases.

PMID- 20823342
TI  - Smoking and risk for diabetes incidence and mortality in Korean men and women.
AB  - OBJECTIVE: Mounting evidence suggests that smoking is a cause of type 2 diabetes.
      We explored the association of cigarette smoking with diabetes incidence and
      mortality in a large cohort of Koreans. RESEARCH DESIGN AND METHODS: A 14-year
      prospective cohort study was performed on 1,236,443 Korean men and women, aged 30
      95 years at baseline, who underwent standardized biennial medical examinations
      provided by the National Health Insurance Corporation (NHIC). Incident diabetes
      was identified on the basis of outpatient visits, hospitalization, or
      prescription medication treatment for diabetes, as captured in the NHIC database.
      Diabetes mortality was obtained through the national statistical office. Cox
      proportional hazards models were used to investigate associations of smoking with
      indicators of diabetes and diabetes mortality. RESULTS: Smoking was significantly
      associated with increased risk for diabetic outpatient treatment,
      hospitalization, and mortality among both men and women, and the risk among
      current smokers increased modestly with the number of cigarettes smoked daily
      (P(trend) < 0.0001 for all associations). Compared with never smokers, current
      male smokers who smoked >= 20 cigarettes/day had increased risk for incident
      diabetes defined by outpatient treatment (adjusted hazard ratio 1.55 [1.51
      1.60]), incident diabetes defined by >= 3 prescription medications for diabetes
      (1.71 [1.63-1.80]), and death from diabetes (1.60 [1.25-2.06]). The risks for
      outpatient treatment among smokers were higher in men than in women with evidence
      for effect modification by sex and age (P(interaction) < 0.0001). CONCLUSIONS:
      Our study provides longitudinal evidence that smoking increases the risk of
      incident diabetes and mortality.

PMID- 20823343
TI  - Antidepressant medication use, weight gain, and risk of type 2 diabetes: a
      population-based study.
AB  - OBJECTIVE: To examine antidepressant medication use as a risk factor for type 2
      diabetes and weight gain. RESEARCH DESIGN AND METHODS: A series of nested studies
      within a prospective cohort of 151,347 working-aged men and women including 9,197
      participants with continuing antidepressant medication, 224 with severe
      depression, and 851 with incident type 2 diabetes during a mean follow-up of 4.8
      years, as indicated by national health and prescription registers (the Public
      Sector study, Finland 1995-2005). RESULTS: In the first analysis, the case
      subjects were individuals with incident type 2 diabetes compared with matched
      diabetes-free control subjects. Antidepressant use of >= 200 defined daily doses
      was associated with a doubling of diabetes risk in both participants with no
      indication of severe depression (odds ratio 1.93 [95% CI 1.48-2.51]) and
      participants with severe depression (2.65 [1.31-5.39]). In further analyses, the
      exposed group was antidepressant users and the reference group was nonusers
      matched for depression-related characteristics. The 5-year absolute risk of
      diabetes was 1.1% for nonusers, 1.7% for individuals treated with 200-399 defined
      daily doses a year, and 2.3% for those with >= 400 defined daily doses (P(trend)
      < 0.0001). An average self-reported weight gain, based on repeated surveys, was
      1.4 kg (2.5%) among nonusers and 2.5 kg (4.3%) among users of >= 200 defined
      daily doses (P(trend) < 0.0001). Separate analyses for tricyclic antidepressants
      and selective serotonin reuptake inhibitors replicated these findings.
      CONCLUSIONS: In these data, continuing use of antidepressant medication was
      associated with an increased relative risk of type 2 diabetes, although the
      elevation in absolute risk was modest.

PMID- 20823344
TI  - Patient age, ethnicity, medical history, and risk factor profile, but not drug
      insurance coverage, predict successful attainment of glycemic targets: Time 2 Do
      More Quality Enhancement Research Initiative (T2DM QUERI).
AB  - OBJECTIVE: To identify factors in patients with type 2 diabetes and A1C >7.0%
      associated with attainment of A1C <= 7.0%. RESEARCH DESIGN AND METHODS: We used a
      prospective registry of 5,280 Canadian patients in primary care settings enrolled
      in a 12-month glycemic pharmacotherapy optimization strategy based on national
      guidelines. RESULTS: At close out, median A1C was 7.1% (vs. 7.8% at baseline)
      with 48% of subjects achieving A1C <= 7.0% (P < 0.0001). Older patients of Asian
      or black origin, those with longer diabetes duration, those with lower baseline
      A1C, BMI, LDL cholesterol, and blood pressure, and those on angiotensin receptor
      blockers and a lower number of antihyperglycemic agents, were more likely to
      achieve A1C <= 7.0% at some point during the study (all P < 0.0235). Access to
      private versus public drug coverage did not impact glycemic target realization.
      CONCLUSIONS: Patient demography, cardiometabolic health, and ongoing
      pharmacotherapy, but not access to private drug insurance coverage, contribute to
      the care gap in type 2 diabetes.

PMID- 20823345
TI  - Effects of thyroid hormone on A1C and glycated albumin levels in nondiabetic
      subjects with overt hypothyroidism.
AB  - OBJECTIVE: We aimed to determine the effects of thyroid hormone on A1C and
      glycated albumin (GA) in nondiabetic patients with overt hypothyroidism. RESEARCH
      DESIGN AND METHODS: A1C levels were measured in 45 nondiabetic patients with
      overt hypothyroidism and 180 euthyroid control subjects. A1C, GA, fasting blood
      glucose (FBG), 1,5-anhydroglucitol, and erythrocyte indexes were determined in 30
      nondiabetic patients with overt hypothyroidism before and after thyroid hormone
      replacement. RESULTS: A1C levels were higher in patients with hypothyroidism
      compared with control subjects. A1C levels were decreased by thyroid hormone
      replacement. Thyroid hormone replacement increased serum erythropoietin,
      reticulocyte count, and mean corpuscular hemoglobin (MCH). The change in A1C
      level was significantly correlated with the change in reticulocyte count or MCH.
      Thyroid hormone replacement decreased serum levels of albumin and GA. However,
      FBG and 1,5-anhydroglucitol levels were not altered. CONCLUSIONS: Levels of A1C
      and GA are spuriously high in nondiabetic patients with overt hypothyroidism.

PMID- 20823346
TI  - Low peripheral nerve conduction velocities and amplitudes are strongly related to
      diabetic microvascular complications in type 1 diabetes: the EURODIAB Prospective
      Complications Study.
AB  - OBJECTIVE: Slow nerve conduction velocity and reduction in response amplitude are
      objective hallmarks of diabetic sensorimotor polyneuropathy. Because subjective
      or clinical indicators of neuropathy do not always match well with the presence
      of abnormal nerve physiology tests, we evaluated associations to nerve conduction
      in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Nerve conduction
      studies were performed in the distal sural and ulnar sensory nerves and the
      peroneal motor nerve in 456 individuals with type 1 diabetes who participated in
      the follow-up visit of the EURODIAB Prospective Complications Study (EPCS). We
      used multivariate regression models to describe associations to decreased nerve
      conduction measures. RESULTS: In addition to an effect of duration of diabetes
      and A1C, which were both associated with low nerve conduction velocity and
      response amplitude, we found that the presence of nephropathy, retinopathy, or a
      clinical diagnosis of neuropathy was associated with low nerve conduction
      velocity and amplitude. In the case of nonproliferative retinopathy, the odds
      ratio (OR) for being in lowest tertile was 2.30 (95% CI 1.13-4.67) for nerve
      conduction velocity. A similar OR was found for each 2% difference in A1C (2.39
      [1.68-3.41]). CONCLUSIONS: We show that the presence of other microvascular
      diabetes complications, together with diabetes duration and A1C, are associated
      with low nerve conduction velocity and amplitude response and that cardiovascular
      disease or risk factors do not seem to be associated with these measures.

PMID- 20823347
TI  - Preterm birth--a risk factor for type 2 diabetes? The Helsinki birth cohort
      study.
AB  - OBJECTIVE: The association between low birth weight and type 2 diabetes is well
      established. We studied whether preterm birth carries a similar risk. RESEARCH
      DESIGN AND METHODS: The Helsinki Birth Cohort includes 13,345 men and women born
      between 1934 and 1944. Of them, 12,813 had adequate data on length of gestation,
      which we linked with data on special reimbursement for diabetes medication.
      RESULTS: Of the subjects, 5.1% had received special reimbursement after age 40.
      In subjects born before 35 weeks of gestation, the odds ratio for diabetes was
      1.68 (95% CI 1.06-2.65) compared with that in those born at term. After
      adjustment for birth weight relative to length of gestation, the odds ratio was
      1.59 (1.00-2.52). CONCLUSIONS: Preterm birth before 35 weeks of gestation is
      associated with an increased risk of type 2 diabetes in adult life. The risk is
      independent of that associated with slow fetal growth.

PMID- 20823348
TI  - The words we use, the procedures we do, and how we change (medical care
      information for family physicians).

PMID- 20823349
TI  - Re: nasolaryngoscopy in a family medicine clinic: indications, findings, and
      economics.

PMID- 20823350
TI  - From bench to clinic: accessing promising investigational medications for
      patients with HIV infection in an urban family health center.
AB  - BACKGROUND: Patients who experience failure of treatment for human
      immunodeficiency virus and who have no other treatment options can sometimes
      obtain promising investigational medications through expanded access programs.
      However, psychosocial and socioeconomic factors, common among underserved
      populations, create barriers to enrollment at referral centers. To increase
      access for unstable patients, an urban family health center developed the
      capacity to provide investigational medications directly to patients. This
      article describes that process and the treatment outcomes. METHODS: The necessary
      steps to implement the program were outlined and accomplished. Patient outcomes
      were analyzed and the project's value to the organization and its clients was
      evaluated. RESULTS: Twenty-five patients received one or more investigational
      antiretroviral medications. Within 24 weeks of enrollment, the majority of
      patients achieved undetectable viral levels (80% achieved <400 copies/mL and 64%
      achieved <50 copies/mL), with a median decrease of 49,173 copies/mL (P = .0002)
      and a median increase in CD4 lymphocyte count of 95 cells/mm(3) (P < .0001).
      CONCLUSION: Community health centers can mitigate barriers to access and meet the
      needs of unstable patients who have no therapeutic options by incorporating
      access to promising investigational treatments into primary care. The use of
      centralized institutional review boards can increase efficiency of the review
      process, but provisions to address local cultural and social issues should be
      included.

PMID- 20823351
TI  - Effects of labeling patients as prehypertensive.
AB  - BACKGROUND: Labeling patients as hypertensive has some negative effects. The
      effects of being labeled as having prehypertension are unknown. We examined
      whether the label of prehypertension exerts a negative effect on patients'
      perceived health and whether it motivates people to adopt lifestyle
      recommendations to prevent hypertension. METHODS: We randomized 97
      prehypertensive adults to either a labeling message or a generic (no label)
      message. At 3 months we assessed self-reports of change in perceived health and
      reported adoption of lifestyle recommendations to try to prevent hypertension.
      RESULTS: Except for more participants with asthma in the label group, the 2
      groups were similar at baseline. Among the 70 participants who provided 3-month
      follow-up data, 18 people (56%) in the no-label group and 22 people (58%) in the
      label group reported their health as the same; 13 people (41%) in the no label
      group and 16 people (42%) in the label group reported health as better; and 1
      person (in no label group) reported his health as worse. At 3 months there were
      no differences in reports of changing eating habits (risk ratio [RR], 1.06; 95%
      CI, 0.86-1.31), cutting down on salt (RR, 0.99; 95% CI, 0.84-1.15), reducing
      alcohol intake (RR, 1.23; 95% CI, 0.80-1.90), or exercising (RR, 1.17; 95% CI,
      0.91-1.51) to try to prevent hypertension. CONCLUSION: Being labeled as
      prehypertensive seems to exert neither harmful nor helpful effects.

PMID- 20823352
TI  - Clinical outcomes of electrodiagnostic testing conducted in primary care.
AB  - BACKGROUND: Focal and generalized neuropathies, such as carpal tunnel syndrome
      and diabetic peripheral neuropathy, have high prevalence among the US population.
      Primary care physicians are increasingly using computerized electrodiagnostic
      (EDX) testing to evaluate these patients. The impact of this diagnostic modality
      on physician diagnostic reasoning and patient management has not been directly
      studied. METHODS: Consecutive computerized EDX tests conducted in a primary care
      clinic were prospectively evaluated using a diagnostic before-and-after study
      design. The pretest diagnosis and patient management plan were noted before EDX
      testing. Five clinical outcomes were assessed after the test: (1) test
      abnormality, (2) confirmation of pretest diagnosis, (3) change in pretest
      diagnosis, (4) expansion of pretest diagnosis, and (5) change to patient
      management plan. RESULTS: One hundred computerized EDX tests were performed among
      85 patients. A total of 88 tests were abnormal. The pretest diagnosis was
      confirmed in 59 tests. The pretest diagnosis was changed by 14 tests and it was
      expanded by 18 tests. The computerized EDX tests triggered a change in clinical
      management in 30 cases, with referral to orthopedic surgery and metabolic workup
      for polyneuropathy as the most common changes. CONCLUSIONS: Computerized EDX
      testing was clinically valuable in patients with moderate to high pretest
      probability of common neuropathies such as carpal tunnel syndrome and diabetic
      polyneuropathy. In approximately one third of cases, the test led to a change in
      clinical management.

PMID- 20823353
TI  - Nasolaryngoscopy in a family medicine clinic: indications, findings, and
      economics.
AB  - BACKGROUND: Nasopharyngeal complaints are common among patients who present to
      primary care. Patients with these complaints are often referred for
      nasolaryngoscopy evaluation to exclude serious conditions such as laryngeal
      cancer. METHODS: This study is a retrospective case series in which 276 charts of
      adult outpatients who were referred for nasolaryngoscopy were reviewed. We
      examined patient demographics, procedure indications and findings, complications,
      and changes in clinical management. RESULTS: Nasolaryngoscopy was completed in
      273 (98.9%) patients (mean age, 51.3 +/- 14.6 years; 71.4% were women). The most
      common indications for nasolaryngoscopy were hoarseness (51.3%), globus sensation
      (32.0%), and chronic cough (17.1%); the most common findings included
      laryngopharyngeal reflux (42.5%), chronic rhinitis (32.2%), and vocal cord
      lesions (13.2%). Three patients (1.1%) were diagnosed with laryngeal cancer and
      this diagnosis was significantly associated with a history of smoking (P = .03).
      No major complications occurred. CONCLUSIONS: We found that nasolaryngoscopy was
      a safe procedure in the primary care setting, and no major complications occurred
      in our series. Patients who have ever smoked and complain of hoarseness are at
      higher risk for laryngeal cancer. An alarming 1% of patients in our series were
      diagnosed with laryngeal cancer. This is the first study to define the rates of
      laryngopharyngeal reflux, vocal cord lesions, and laryngeal cancer among primary
      care patients.

PMID- 20823354
TI  - Sustainability of depression care improvements: success of a practice change
      improvement collaborative.
AB  - BACKGROUND: Long-term sustainment of improvements in care continues to challenge
      primary care practices. During the 2 years after of our Improving Depression Care
      collaborative, we examined how well practices were sustaining their depression
      care improvements. METHODS: Our study design used a qualitative interview follow
      up of a modified learning collaborative intervention. We conducted telephone
      interviews with practice champions from 15 of the original 16 practices.
      Interviews were conducted during a 3-month period in 2008, and were recorded and
      professionally transcribed. Data on each of the depression care improvements and
      the change management strategy emphasized during the learning collaborative were
      summarized after review of the primary data and a consensus process to resolve
      differing interpretations. RESULTS: During the period from 15 months to 3 years
      since our project began, depression screening or case finding was sustained in 14
      of 15 practices. Thirteen practices sustained use of the 9-item Patient Health
      Questionnaire for depression monitoring, and one additional practice initiated
      it. Seven practices initiated self-management support and 2 of 3 practices
      sustained it. In contrast, tracking and case management proved difficult to
      sustain, with only 4 of 8 practices continuing this activity. Diffusion of use of
      the 9-item Patient Health Questionnaire to other clinicians in the practice was
      maintained in all but 3 practices and expanded in one practice. Six of the
      practices continued to use the change management strategy, including all 4 of the
      practices that sustained tracking. CONCLUSIONS: Practices demonstrated long-term
      sustained improvement in depression care with the exception of tracking and care
      management, which may be a more challenging innovation to sustain. We hypothesize
      that sustaining complex depression care innovations may require active management
      by the practice.

PMID- 20823355
TI  - What words should we use when discussing excess weight?
AB  - BACKGROUND: There is limited research on how patients prefer physicians to
      communicate about the topic of obesity, and there is even less understanding of
      which terms physicians most commonly use. METHODS: In this cross-sectional,
      nonrandom sampling study, patients who were seeking treatment for weight loss
      rated the desirability of 12 terms to describe excess weight, and physicians
      rated the likelihood with which they would use those terms during clinical
      encounters. Participants rated terms on a 5-point scale, with -2 representing
      "very undesirable" or "definitely would not use" and +2 representing "very
      desirable" or "definitely would use." RESULTS: Patients (n = 143; mean age, 46.8
      years; mean body mass index, 36.9 kg/m(2)) rated "weight" (mean +/- SD) as the
      most desirable term (1.13 +/- 1.10), although it did not significantly differ
      from 5 other terms provided. They rated "fatness" (-1.30 +/- 1.22) as the most
      undesirable term, although this rating did not differ significantly from 4 other
      terms. Physicians affiliated with a community-based medical school (n = 108; mean
      age, 48.8 years; 79.6% primary care specialty) were most likely to use "weight"
      (1.42 +/- 0.89), which was significantly different from ratings for all other
      terms. They were least likely to use "fatness" (-1.74 +/- 0.59), although this
      rating did not differ significantly from 3 other terms. CONCLUSION: Physicians
      generally reported that they use terminology that patients had rated more
      favorably, and they tend to avoid terms that patients may find undesirable.
      Understanding the preferences and terminology used by patients and physicians is
      an important initial step to ensure that communications related to obesity and
      weight loss are efficient and effective.

PMID- 20823356
TI  - Assessing safe and independent living in vulnerable older adults: perspectives of
      professionals who conduct home assessments.
AB  - OBJECTIVES: The objectives of this study were to describe social services and
      health professionals' perceptions of vulnerability among older adults living in
      the community and to elicit how these professionals screen vulnerability in
      community and in-home settings. METHODS: Focus group sessions were conducted and
      analyzed using standardized methods of qualitative analysis. Participants
      included social services and health professionals (n = 45) who routinely
      encounter vulnerable older adults. RESULTS: Four themes characterized
      vulnerability: the inability to perform activities of daily living, lack of
      social support, sociodemographic factors, and neuropsychiatric conditions. When
      screening older adults, participants reported evaluating basic cognitive
      abilities, decision-making processes, and the capacity to adequately plan and
      safely perform everyday tasks. Participants stated that screening is best
      performed by an interdisciplinary team in the home setting and preferably on more
      than one occasion. CONCLUSIONS: Social services and health professionals in this
      study described routinely screening for vulnerability in community-living older
      adults using a multidomain approach. These professionals endorse the use of
      assessments that screen an older adult's cognitive and functional capacities for
      safe and independent living. Further research is needed that integrates routine
      screening for vulnerability by community social services professionals with the
      assessments and interventions conducted by primary care physicians.

PMID- 20823357
TI  - Effect of financial incentives on improvement in medical quality indicators for
      primary care.
AB  - PURPOSE: The efficacy of rewarding physicians financially for preventive services
      is unproven. The objective of this study was to evaluate the effect of a
      physician pay-for-performance program similar to the Medicare Physician Quality
      Reporting Initiative program on quality of preventive care in a network of
      community health centers. METHODS: A retrospective review of administrative data
      was done to evaluate a natural quasi-experiment in a network of publicly funded
      primary care clinics. Physicians in 6 of 11 clinics were given a financial
      incentive twice the size of the current Centers for Medicare and Medicaid
      Services' incentive for achieving group targets in preventive care that included
      cervical cancer screening, mammography, and pediatric immunization. They also
      received productivity incentives. Six years of performance indicators were
      compared between incentivized and nonincentivized clinics. We also surveyed the
      incentivized clinicians about their perception of the incentive program. RESULTS:
      Although some performance indicators improved for all measures and all clinics,
      there were no clinically significant differences between clinics that had
      incentives and those that did not. A linear trend test approached conventional
      significance levels for Papanicolaou smears (P = .08) but was of very modest
      magnitude compared with observed nonlinear variations; there was no suggestion of
      a linear trend for mammography or pediatric immunizations. The survey revealed
      that most physicians felt the incentives were not very effective in improving
      quality of care. CONCLUSION: We found no evidence for a clinically significant
      effect of financial incentives on performance of preventive care in these
      community health centers. Based on our findings and others, we believe there is
      great need for more research with strong research designs to determine the
      effects, both positive and negative, of financial incentives on clinical quality
      indicators in primary care.

PMID- 20823358
TI  - It takes two: using coleaders to champion improvements in small primary care
      practices.
AB  - BACKGROUND: Making the kind of improvement changes necessary to move toward a
      patient-centered medical home will continue to challenge small, independent
      primary care practices. Here we describe further analysis of a successful program
      to understand the roles of coleaders of a change management process. METHODS:
      Through an improvement collaborative we trained 2 coleaders (a physician and a
      non-physician) from 16 small primary care practices to institute depression care
      improvements. These coleaders participated in 3 learning sessions that provided
      depression care content as well as skills to implement a change management
      strategy. Qualitative data were collected by observation during the learning
      sessions and through in-depth interviews conducted at baseline, between each
      learning session, at the end of the project, 6 months after the project ended,
      and, finally, 26 months after the project's end. RESULTS: Interview results with
      the coleaders affirmed that a team approach is a viable strategy for practice
      improvement. The 2 coleaders used their complementary skills, relationships, and
      credibility among the practice staff to implement and sustain practice
      improvements. In their differing roles, they varied in how they perceived
      barriers to change and how they assessed their team's progress. CONCLUSIONS:
      Involving both a physician and a non-physician as coleaders enables improvement
      teams in small primary care practices to make progress both in the clinical
      content of their work and in the critical change management activities involved
      with creating a team, managing meetings, and coordinating work between meetings.
      Using a coleader structure enriches the improvement process, broadens
      participation in the change process, and helps to sustain these efforts over
      time.

PMID- 20823359
TI  - Dry needling in the management of musculoskeletal pain.
AB  - Myofascial pain is a common syndrome seen by family practitioners worldwide. It
      can affect up to 10% of the adult population and can account for acute and
      chronic pain complaints. In this clinical narrative review we have attempted to
      introduce dry needling, a relatively new method for the management of
      musculoskeletal pain, to the general medical community. Different methods of dry
      needling, its effectiveness, and physiologic and adverse effects are discussed.
      Dry needling is a treatment modality that is minimally invasive, cheap, easy to
      learn with appropriate training, and carries a low risk. Its effectiveness has
      been confirmed in numerous studies and 2 comprehensive systematic reviews. The
      deep method of dry needling has been shown to be more effective than the
      superficial one for the treatment of pain associated with myofascial trigger
      points. However, over areas with potential risk of significant adverse events,
      such as lungs and large blood vessels, we suggest using the superficial
      technique, which has also been shown to be effective, albeit to a lesser extent.
      Additional studies are needed to evaluate the effectiveness of dry needling.
      There also is a great need for further investigation into the development of pain
      at myofascial trigger points.

PMID- 20823360
TI  - Lifetime follow-up care after childhood cancer.
AB  - Cancers that occur during childhood and adolescence (ages 0 to 19 years) are very
      responsive to treatment, with a current overall cure rate of better than 80%.
      However, approximately 75% of childhood cancer survivors develop late effects,
      including problems with growth and development, vital organ function,
      reproduction, and psychological health, as well as serious complications of
      secondary neoplasms and recurrence. The primary physician should continue some
      level of involvement during all phases of patient care and pay special attention
      to possible late effects during the follow-up phase.

PMID- 20823361
TI  - Systematic review of health information exchange in primary care practices.
AB  - BACKGROUND: Unprecedented federal interest and funding are focused on secure,
      standardized, electronic transfer of health information among health care
      organizations, termed health information exchange (HIE). The stated goals are
      improvements in health care quality, efficiency, and cost. Ambulatory primary
      care practices are essential to this process; however, the factors that motivate
      them to participate in HIE are not well studied, particularly among small
      practices. METHODS: We conducted a systematic review of the literature about HIE
      participation from January 1990 through mid-September 2008 to identify peer
      reviewed and non-peer-reviewed publications in bibliographic databases and
      websites. Reviewers abstracted each publication for predetermined key issues,
      including stakeholder participation in HIE, and the benefits, barriers, and
      overall value to primary care practices. We identified themes within each key
      issue, then grouped themes and identified supporting examples for analysis.
      RESULTS: One hundred and sixteen peer-reviewed, non-peer-reviewed, and web
      publications were retrieved, and 61 met inclusion criteria. Of 39 peer-reviewed
      publications, one-half reported original research. Among themes of cost savings,
      workflow efficiency, and quality, the only benefits to be reliably documented
      were those regarding efficiency, including improved access to test results and
      other data from outside the practice and decreased staff time for handling
      referrals and claims processing. Barriers included cost, privacy and liability
      concerns, organizational characteristics, and technical barriers. A positive
      return on investment has not been documented. CONCLUSIONS: The potential for HIE
      to reduce costs and improve the quality of health care in ambulatory primary care
      practices is well recognized but needs further empiric substantiation.

PMID- 20823362
TI  - Refusal: deciding to pull the tube.
AB  - A senior medical student grapples with her patient's end-of-life decisions, which
      are in stark contrast to the decisions made by her own grandfather facing a
      similar disease. As she explores her role and responsibility to her patient, she
      considers what it means to provide futile care and how to negotiate her own
      beliefs with the demands of her patient's family.

PMID- 20823363
TI  - The dilemma of goodness: acknowledging beneficence tension in the search for
      consensus.
AB  - Patient care in family medicine and palliative medicine involves important
      communication with stakeholders. Beneficence is assumed to be crucial to
      achieving consensus in these encounters. However, stakeholders may have different
      perspectives of beneficence. The term beneficence tension is introduced to
      conceptualize these differing perspectives. Acknowledging beneficence tension is
      suggested as a way to enhance effective communication with patients and families.

PMID- 20823364
TI  - Primary hyperparathyroidism as a secondary cause of depression.
AB  - A 27-year-old woman was initially diagnosed and treated for depression with
      suicide ideation. Thirteen months later, kidney stones, an elevated parathyroid
      hormone, and elevated calcium levels led to a diagnosis of primary
      hyperparathyroidism. The patient was treated for hyperparathyroidism by resection
      of the superior right parathyroid gland. When the calcium levels were regulated,
      the patient's moods, concentration, and memory were back to baseline.

PMID- 20823365
TI  - Intermittent diarrhea as a delayed presentation of percutaneous endoscopic
      gastrostomy (PEG)-associated fistula.
AB  - A 60-year-old patient with severe dysphagia, weight loss, and recurrent
      aspiration pneumonia required a percutaneous endoscopic gastrostomy (PEG) for
      long-term feeding. After 24 uneventful days, she developed an enigmatic recurring
      but intermittent diarrhea. On day 62, staff noted a feculent odor from her
      gastrostoma, along with undigested formula in her stools. This prompted her
      hospitalization. A plain abdominal radiograph demonstrated the PEG tube in the
      upper abdomen, but could not differentiate if its tip was misplaced. Next, an
      abdominal barium-contrast computed tomography scan was performed but was
      inadvertently misinterpreted as normal. Finally, a colonoscopy demonstrated that
      the tip of the PEG tube was malpositioned in the transverse colon, resulting in a
      colocutaneous fistula (CCF). The PEG tube was withdrawn uneventfully through the
      gastrostoma. A laparotomy was performed. Strong adhesions were found between the
      stomach and the colon; these were lysed and the CCF tract was excised. The
      patient recovered. CCF should be considered in the differential diagnosis of PEG
      patients with unexplained diarrhea even if the diarrhea is delayed or
      intermittent; the diagnosis should be confirmed by a tubogram.

PMID- 20823366
TI  - Cat scratch disease and arthropod vectors: more to it than a scratch?
AB  - PURPOSE: Cat scratch disease is a common infection, particularly in children, and
      clinicians need to be aware of its potential transmission to humans by arthropod
      vectors such as fleas and ticks in addition to animal bites and scratches. The
      absence of a vertebrate bite or scratch does not preclude infection with
      Bartonella henselae. METHODS: Literature regarding arthropod transmission of B.
      henselae was reviewed. RESULTS: B. henselae and related bacterial species are
      transmitted among cats and dogs by arthropod vectors. In the absence of these
      vectors, disease does not spread amongst the animals. On the other hand, disease
      can be spread to humans by bite and scratch as well as by arthropod vectors.
      Animals commonly infected with B. henselae and arthropod vectors are discussed.
      CONCLUSIONS: Clinicians should be aware that a common illness, cat scratch
      disease, can be transmitted by arthropod vectors and a history of an animal
      scratch or bite is not necessary for disease transmission.

PMID- 20823367
TI  - Re: future of board certification in a new era of public accountability.

PMID- 20823368
TI  - Re: parental acceptance of a mandatory human papillomavirus (HPV) vaccination
      program.

PMID- 20823369
TI  - Re: a randomized, controlled trial of a behavioral intervention to reduce crying
      among infants.

PMID- 20823371
TI  - Properties of silkworm Na+/K+-ATPase.
AB  - The high Na(+) and low K(+) concentrations in mammalian blood are maintained by
      Na(+)/K(+)-ATPase. In contrast, the K(+) concentration is higher than the Na(+)
      concentration in the hemolymph of the silkworm Bombyx mori, a Lepidopterous
      insect. Although Na(+)/K(+)-ATPase, therefore, appears not to be in silkworm, we
      confirmed the presence of Na(+)/K(+)-ATPase in nerve tissues of silkworm but not
      in skeletal muscle or the dorsal vessel. The enzymatic properties of silkworm
      Na(+)/K(+)-ATPase were characterized in detail and compared with those of dog
      Na(+)/K(+)-ATPase. Silkworm Na(+)/K(+)-ATPase had a much lower affinity for K(+)
      and a somewhat higher affinity for Na(+) than dog Na(+)/K(+)-ATPase. The optimal
      temperature of silkworm Na(+)/K(+)-ATPase activity was lower than that of dog
      Na(+)/K(+)-ATPase. The optimal Mg(2+) concentration, pH and sensitivities to
      Ca(2+) and ouabain, a specific inhibitor of Na(+)/K(+)-ATPase, of the two ATPases
      were identical. These results indicate that the enzymatic properties of the
      silkworm Na(+)/K(+)-ATPase are suitable for its growth, despite the differences
      between dog and silkworm Na(+)/K(+)-ATPases. Antisera raised against dog
      Na(+)/K(+)-ATPase recognized only the alpha-subunit of silkworm Na(+)/K(+)
      ATPase.

PMID- 20823370
TI  - Functional proteomic analysis of promyelocytic leukaemia nuclear bodies in
      irradiation-induced MCF-7 cells.
AB  - It is well established that promyelocytic leukaemia nuclear bodies (PML NBs) play
      important roles in DNA damage responses (DDR). After irradiation, PML NBs
      dynamically recruit or release important proteins involved in cell-cycle
      regulation, DNA repair and apoptosis. As PML protein is the key molecule of PML
      NBs' dynamic assembling, we aimed to characterize the PML-interacting proteins in
      (60)Co-irradiated MCF-7 cells. A proteomic approach using CoIP, mono-dimensional
      electrophoresis and tandem mass spectrometry, allowed us to identify a total of
      124 proteins that may associate with PML after irradiation. Bioinformatic
      analysis of the identified proteins showed that most of them were related to
      characterized PML functions, such as transcriptional regulation, cell-cycle
      regulation, cell-death regulation and response to stress. Four proteins, B23,
      MVP, G3BP1 and DHX9, were verified to co-localize with PML differentially before
      and after ionizing radiation (IR) treatment. The proteins identified in this
      study will significantly improve our understanding of the dynamic organization
      and multiple functions of PML NBs in DDR.

PMID- 20823372
TI  - Self-embedding behavior: radiologic management of self-inserted soft-tissue
      foreign bodies.
AB  - PURPOSE: To report on a series of self-embedding behavior (SEB), demonstrate the
      effectiveness and clinical effect of image-guided foreign body removal (IGFBR) in
      the treatment of embedded soft-tissue foreign bodies (STFBs), and evaluate the
      role of the radiologist in the clinical management of SEB. MATERIALS AND METHODS:
      This retrospective study was approved by the institutional review board. From a
      database of 600 patients treated with IGFBR with ultrasonographic (US) and/or
      fluoroscopic guidance, self-injury was identified in 11 (1.8%) mainly adolescent
      patients with a mean age of 16 years (age range, 14-18 years). Evaluated data
      included number of foreign bodies; number of repeat episodes of foreign body
      insertion; location, type, and size of foreign body; incision size; imaging
      modality; and success or failure of foreign body removal. RESULTS: Seventy-six
      foreign bodies were inserted into the arm (n = 69), neck (n = 4), ankle (n = 1),
      foot (n = 1), or hand (n = 1) in the 11 patients. The number of STFBs per case
      ranged from one to 15. Foreign body types included metal (n = 40), plastic (n =
      15), graphite (n = 12), glass (n = 4), wood (n = 3), crayon (n = 1), and stone (n
      = 1). STFB dimensions were 2.5-160.0 mm in length by 0.25-3.0 mm in thickness.
      Sixty-eight of the 76 STFBs were removed in the interventional radiology section.
      Incision lengths ranged from 4 to 8 mm (mean, 6 mm). The STFBs were removed with
      US guidance (n = 43), fluoroscopic guidance (n = 15), or a combination of the two
      modalities (n = 10). IGFBR was successful in all 68 cases, without complications.
      CONCLUSION: Greater awareness of SEB may result in radiologists being the first
      physicians to identify SEB and rapidly mobilize an interdisciplinary team for
      early and effective intervention and treatment. Percutaneous radiologic treatment
      of self-imbedded STFBs is safe, precise, and effective for radiopaque and
      nonradiopaque foreign bodies.

PMID- 20823373
TI  - Origin of clothing lice indicates early clothing use by anatomically modern
      humans in Africa.
AB  - Clothing use is an important modern behavior that contributed to the successful
      expansion of humans into higher latitudes and cold climates. Previous research
      suggests that clothing use originated anywhere between 40,000 and 3 Ma, though
      there is little direct archaeological, fossil, or genetic evidence to support
      more specific estimates. Since clothing lice evolved from head louse ancestors
      once humans adopted clothing, dating the emergence of clothing lice may provide
      more specific estimates of the origin of clothing use. Here, we use a Bayesian
      coalescent modeling approach to estimate that clothing lice diverged from head
      louse ancestors at least by 83,000 and possibly as early as 170,000 years ago.
      Our analysis suggests that the use of clothing likely originated with
      anatomically modern humans in Africa and reinforces a broad trend of modern human
      developments in Africa during the Middle to Late Pleistocene.

PMID- 20823374
TI  - Effects of 2-bromoethanamine on TonEBP expression and its possible role in
      induction of renal papillary necrosis in mice.
AB  - Chronic analgesic abuse has been shown to induce severe renal injury
      characterized by renal papillary necrosis (RPN), an injury detectable at late
      stage. While direct toxicity of the drug may exist, the molecular mechanisms
      underlying analgesics induction of RPN remain unknown. A major limitation to
      study the pathogenesis of RPN is the required chronic exposure before detection
      of injury. Here, we employed 2-bromoethanamine (BEA) to simulate rapid papillary
      toxicity using inner medullary collecting duct (IMCD3) cells. Although exposure
      to 10MUM BEA had no effect on cellular viability under isotonic conditions, a 50%
      loss in cell viability was observed in the first 24 h when cells were subjected
      to sublethal hypertonic stress and nearly complete cell death after 48 h
      suggesting that BEA exerts cytotoxicity only under hypertonic conditions. Because
      TonEBP is a transcription factor critical for cell survival during hypertonic
      conditions, we undertook experiments to examine the effect of BEA on TonEBP
      expression and activity. Exposure of cells to 10MUM BEA resulted in a substantial
      reduction in TonEBP protein expression after 24 h. In addition, TonEBP was not
      translocated to the nucleus in BEA-treated IMCD3 cells under acute hypertonic
      stress for transcription of target genes essential for osmolyte accumulation.
      Finally, we found a substantial decrease in TonEBP expression in medullary kidney
      tissues of mice injected with a single ip dose of BEA. Our data suggest that
      TonEBP is a potential target for BEA leading to the process of papillary necrosis
      in the settings of hypertonic stress.

PMID- 20823376
TI  - Acute stroke: lower blood pressure looks better and better.

PMID- 20823375
TI  - A population-based study of trends in the use of total hip and total knee
      arthroplasty, 1969-2008.
AB  - OBJECTIVE: To study the rates of use of total hip arthroplasty (THA) and total
      knee arthroplasty (TKA) during the past 4 decades. METHODS: The Rochester
      Epidemiology Project was used to identify all Olmsted County, Minnesota,
      residents who underwent THA or TKA from January 1, 1969, through December 31,
      2008. We used a population-based approach because few data are available on long
      term trends in the use of THA and TKA in the United States. Rates of use were
      determined by age- and sex-specific person-years at risk. Poisson regression was
      used to assess temporal trends by sex and age group. RESULTS: The age- and sex
      adjusted use of THA increased from 50.2 (95% confidence interval [CI], 40.5-59.8)
      per 100,000 person-years in 1969-1972 to 145.5 (95% CI, 134.2-156.9) in 2005
      2008, whereas TKA increased markedly from 31.2 (95% CI, 25.3-37.1) per 100,000
      person-years in 1971-1976 to 220.9 (95% CI, 206.7-235.0) in 2005-2008. For both
      procedures, use was greater among females, and the rate generally increased with
      age. CONCLUSION: In this community, TKA and THA use rates have increased steadily
      since the introduction of the procedures and continue to increase for all age
      groups. On the basis of these population-based data, the probable need for TKA
      and THA exceeds current federal agency projections.

PMID- 20823377
TI  - Effects on peripheral and central blood pressure of cocoa with natural or high
      dose theobromine: a randomized, double-blind crossover trial.
AB  - Flavanol-rich cocoa products have been reported to lower blood pressure. It has
      been suggested that theobromine is partially responsible for this effect. We
      tested whether consumption of flavanol-rich cocoa drinks with natural or added
      theobromine could lower peripheral and central blood pressure. In a double-blind,
      placebo-controlled 3-period crossover trial we assigned 42 healthy individuals
      (age 62+/-4.5 years; 32 men) with office blood pressure of 130 to 159 mm Hg/85 to
      99 mm Hg and low added cardiovascular risk to a random treatment sequence of
      dairy drinks containing placebo, flavanol-rich cocoa with natural dose consisting
      of 106 mg of theobromine, or theobromine-enriched flavanol-rich cocoa with 979 mg
      of theobromine. Treatment duration was 3 weeks with a 2-week washout. The primary
      outcome was the difference in 24-hour ambulatory systolic blood pressure between
      placebo and active treatment after 3 weeks. The difference in central systolic
      blood pressure between placebo and active treatment was a secondary outcome.
      Treatment with theobromine-enriched cocoa resulted in a mean+/-SE of 3.2+/-1.1 mm
      Hg higher 24-hour ambulatory systolic blood pressure compared with placebo
      (P<0.01). In contrast, 2 hours after theobromine-enriched cocoa, laboratory
      peripheral systolic blood pressure was not different from placebo, whereas
      central systolic blood pressure was 4.3+/-1.4 mm Hg lower (P=0.001). Natural dose
      theobromine cocoa did not significantly change either 24-hour ambulatory or
      central systolic blood pressure compared with placebo. In conclusion, theobromine
      enriched cocoa significantly increased 24-hour ambulatory systolic blood pressure
      while lowering central systolic blood pressure.

PMID- 20823378
TI  - Cardiovascular consequences of genetic variation at -6/235 in human
      angiotensinogen using "humanized" gene-targeted mice.
AB  - Genetic and functional data support a role for angiotensinogen in blood pressure
      control, and many population studies have suggested that polymorphisms in the
      angiotensinogen gene contribute to hypertension. Two common haplotypes of the
      human angiotensinogen gene are -6A/235T and -6G/235M. To study their
      contributions to blood pressure regulation in a controlled model system, we
      developed triple-transgenic mice expressing either -6A/235T or -6G/235M human
      angiotensinogen, expressing either an overexpressed and poorly regulated (REN9)
      or a tightly regulated (PAC160) human renin, and all carrying a null mutation in
      the endogenous murine angiotensinogen gene. These humanized mice were then
      examined for blood pressure differences at baseline and after a high-salt diet,
      changes in cardiovascular organ weight, and differences in angiotensinogen and
      renin gene expression. Mice expressing the -6G/235M haplotype on the PAC160
      background exhibited increased blood pressure and cardiac hypertrophy at
      baseline. In contrast, all of the mice with the REN9 background had equivalent
      baseline blood pressures. On the REN9 background, there was a greater increase in
      blood pressure in -6A/235T in response to a high-salt diet, providing evidence it
      may be a susceptibility allele. There were no differences in angiotensinogen
      expression between haplotypes on either background strain. The data suggest that
      the impact of angiotensinogen haplotypes on cardiovascular end points may be
      dependent on renin status and environmental influences, such as dietary sodium.
      These insights may help explain the discrepancies among observational studies
      that have examined roles for the -6A/235T and -6G/235M angiotensinogen haplotypes
      in varied human populations.

PMID- 20823379
TI  - Endothelin-1 increases glomerular permeability and inflammation independent of
      blood pressure in the rat.
AB  - Endothelin (ET) 1 is a potent vasoactive peptide implicated in the pathogenesis
      of hypertension and renal disease. The aim of the current study was to test the
      hypotheses that ET-1 increases albumin permeability of glomeruli isolated from
      normal rats and that chronic ET-1 infusion will increase glomerular permeability
      and inflammation independent of blood pressure. Glomerular permeability to
      albumin was determined from the change in glomerular volume induced by exposing
      isolated glomeruli to oncotic gradients. Incubation of glomeruli taken from
      normal rats with ET-1 at a concentration that did not produce direct glomerular
      contraction (1 nmol/L) significantly increased glomerular permeability to
      albumin, reaching a maximum after 4 hours. Chronic ET-1 infusion for 2 weeks in
      Sprague-Dawley rats significantly increased glomerular permeability to albumin
      and nephrin excretion rate, effects that were attenuated in rats given an ET(A)
      receptor antagonist (ABT-627, 5 mg/kg per day). Urinary protein and albumin
      excretion and mean arterial pressure (telemetry) were not changed by ET-1
      infusion. Acute incubation of glomeruli isolated from ET-1-infused rats with the
      selective ET(A) antagonist significantly reduced glomerular permeability to
      albumin, an effect not observed with acute treatment with a selective ET(B)
      antagonist. Chronic ET-1 infusion increased glomerular and plasma soluble
      intercellular adhesion molecule 1 and monocyte chemoattractant protein 1 and
      elevated the number of macrophages and lymphocytes in renal cortices (ED-1 and
      CD3-positive staining, respectively). These effects were all attenuated in rats
      given an ET(A) selective antagonist. These data support the hypothesis that ET-1
      directly increases glomerular permeability to albumin and renal inflammation via
      ET(A) receptor activation independent of changes in arterial pressure.

PMID- 20823380
TI  - Renal ischemia regulates marinobufagenin release in humans.
AB  - Cardiotonic steroids, including marinobufagenin, are a group of new steroid
      hormones found in plasma and urine of patients with congestive heart failure,
      myocardial infarction, and chronic renal failure. In animal studies, partial
      nephrectomy induces marinobufagenin elevation, cardiac hypertrophy, and fibrosis.
      The objective of this study is to test the effect of renal ischemia on
      marinobufagenin levels in humans with renal artery stenosis (RAS). To test this,
      plasma marinobufagenin levels were measured in patients with RAS of the
      Prospective Randomized Study Comparing Renal Artery Stenting With or Without
      Distal Protection, non-RAS patient controls who were scheduled for coronary
      angiography, and normal healthy individuals. Marinobufagenin levels were
      significantly higher in patients with RAS compared with those of the other 2
      groups. Multivariate analysis shows that occurrence of RAS is independently
      related to marinobufagenin levels. In addition, renal artery revascularization by
      stenting partially reversed marinobufagenin levels in the patients with RAS
      (0.77+/-0.06 nmol/L at baseline; 0.66+/-0.06 nmol/L at 24 hours; and 0.61+/-0.05
      nmol/L at 1 month). In conclusion, we have found that marinobufagenin levels are
      increased in patients with RAS, whereas reversal of renal ischemia by stenting
      treatment reduces marinobufagenin levels. These results suggest that RAS-induced
      renal ischemia may be a major cause of marinobufagenin release.

PMID- 20823381
TI  - Lower treatment blood pressure is associated with greatest reduction in hematoma
      growth after acute intracerebral hemorrhage.
AB  - The pilot phase of the Intensive Blood Pressure Reduction in Acute Cerebral
      Haemorrhage Trial (INTERACT) showed that rapid blood pressure (BP) lowering can
      attenuate hematoma growth in acute intracerebral hemorrhage. We sought to define
      the systolic BP level associated with greatest attenuation of hematoma growth.
      INTERACT included 404 patients with computed tomographic-confirmed intracerebral
      hemorrhage, elevated systolic BP (150 to 220 mm Hg), and capacity to commence BP
      lowering treatment within 6 hours of onset. Computed tomography was done at
      baseline and at 24 hours using standardized techniques, with digital images
      analyzed centrally, blinded to clinical data. Associations of baseline and
      achieved on-treatment (mean during the first 24 hours) systolic BP levels with
      the primary outcome of increase in hematoma volume were explored. There were 346
      patients with duplicate computed tomographic scans. There was no significant
      association between baseline systolic BP levels and either the absolute or
      proportional growth in hematoma volume (P trend=0.26 and 0.12, respectively). By
      contrast, achieved on-treatment systolic BP levels in the first 24 hours were
      clearly associated with both absolute and proportional hematoma growth (both P
      trend=0.03). Maximum reduction in hematoma growth occurred in the one third of
      participants with the lowest on-treatment systolic BP levels (median: 135 mm Hg).
      Intensive BP reduction to systolic levels between 130 and 140 mm Hg is likely to
      provide the maximum protection against hematoma growth after intracerebral
      hemorrhage.

PMID- 20823382
TI  - The search for strategies to control hypertension.

PMID- 20823383
TI  - Reoperations after the Ross procedure.

PMID- 20823384
TI  - Genetic deficiency of plasminogen activator inhibitor-1 promotes cardiac fibrosis
      in aged mice: involvement of constitutive transforming growth factor-beta
      signaling and endothelial-to-mesenchymal transition.
AB  - BACKGROUND: Elevated levels of plasminogen activator inhibitor-1 (PAI-1), a
      potent inhibitor of urokinase plasminogen activator and tissue plasminogen
      activator, are implicated in the pathogenesis of tissue fibrosis. Paradoxically,
      lack of PAI-1 in the heart is associated with the development of cardiac fibrosis
      in aged mice. However, the molecular basis of cardiac fibrosis in aged PAI-1
      deficient mice is unknown. Here, we investigated the molecular and cellular bases
      of myocardial fibrosis. METHODS AND RESULTS: Histological evaluation of
      myocardial tissues derived from aged PAI-1-deficient mice revealed myocardial
      fibrosis resulting from excessive accumulation of collagen. Immunohistochemical
      characterization revealed that the levels of matrix metalloproteinase-2, matrix
      metalloproteinase-9, and transforming growth factor-beta1/2 and the number of
      Mac3-positive and fibroblast specific protein-1-positive cells were significantly
      elevated in aged PAI-1-deficient myocardial tissues compared with controls.
      Zymographic analysis revealed that matrix metalloproteinase-2 enzymatic activity
      was elevated in PAI-1-deficient mouse cardiac endothelial cells. Real-time
      quantitative polymerase chain reaction analyses of RNA from myocardial tissues
      revealed the upregulation of profibrotic markers in aged PAI-1-deficient mice.
      The numbers of phosphorylated Smad2-, phosphorylated Smad3-, and phosphorylated
      ERK1/2 MAPK-, but not pAkt/PKB-, positive cells were significantly increased in
      PAI-1-deficient myocardial tissues. Western blot and immunocytochemical analysis
      revealed that PAI-1-deficient mouse cardiac endothelial cells were more
      susceptible to endothelial-to-mesenchymal transition in response to transforming
      growth factor-beta2. CONCLUSIONS: These results indicate that spontaneous
      activation of both Smad and non-Smad transforming growth factor-beta signaling
      may contribute to profibrotic responses in aged PAI-1-deficient mice hearts and
      establish a possible link between endothelial-to-mesenchymal transition and
      cardiac fibrosis in PAI-1-deficient mice.

PMID- 20823385
TI  - Preeclampsia and gestational hypertension are associated with childhood blood
      pressure independently of family adiposity measures: the Avon Longitudinal Study
      of Parents and Children.
AB  - BACKGROUND: Offspring of women with hypertensive disorders of pregnancy are at
      increased risk of cardiovascular complications later in life, but the mechanisms
      underlying these associations are unclear. Our aim was to examine whether
      adjusting for birth weight and familial adiposity changed the association of
      hypertensive disorders of pregnancy with offspring blood pressure. METHODS AND
      RESULTS: Using data from 6343 nine-year-old participants in the Avon Longitudinal
      Study of Parents and Children, we examined the association between hypertensive
      disorders of pregnancy (preeclampsia and gestational hypertension) and offspring
      blood pressure. Both preeclampsia and gestational hypertension were associated
      with systolic and diastolic blood pressures in the 9-year-old offspring; after
      adjustment for parental and own adiposity and for other potential confounders,
      the mean difference in systolic blood pressure was 2.05 mm Hg (95 confidence
      interval, 0.72 to 3.38) and 2.04 mm Hg (95 confidence interval, 1.42 to 2.67) for
      preeclampsia and gestational hypertension, respectively, compared with those with
      no hypertensive disorders of pregnancy. Equivalent results for diastolic blood
      pressure were 1.00 mm Hg (95 confidence interval, -0.01 to 2.10) and 1.07 mm Hg
      (95 confidence interval, 0.60 to 1.54). The association of preeclampsia with
      offspring systolic and diastolic blood pressures attenuated toward the null with
      further adjustment for birth weight and gestational age, whereas these
      adjustments did not attenuate the association of gestational hypertension with
      offspring blood pressure. CONCLUSIONS: The associations of hypertensive disorders
      of pregnancy with higher offspring blood pressure are not explained by familial
      adiposity. The mechanisms linking preeclampsia and gestational hypertension with
      offspring blood pressure may differ, with the former mediated at least in part by
      the effect of preeclampsia on intrauterine growth restriction.

PMID- 20823386
TI  - Association of colony-forming units with coronary artery and abdominal aortic
      calcification.
AB  - BACKGROUND: Certain bone marrow-derived cell populations, called endothelial
      progenitor cells, have been reported to possess angiogenic activity. Experimental
      data suggest that depletion of these angiogenic cell populations may promote
      atherogenesis, but limited data are available on their relation to subclinical
      atherosclerotic cardiovascular disease in humans. METHODS AND RESULTS: We studied
      889 participants of the Framingham Heart Study who were free of clinically
      apparent cardiovascular disease (mean age, 65 years; 55% women). Participants
      underwent endothelial progenitor cell phenotyping with an early-outgrowth colony
      forming unit assay and cell surface markers. Participants also underwent
      noncontrast multidetector computed tomography to assess the presence of
      subclinical atherosclerosis, as reflected by the burden of coronary artery
      calcification and abdominal aortic calcification. Across decreasing tertiles of
      colony-forming units, there was a progressive increase in median coronary artery
      calcification and abdominal aortic calcification scores. In multivariable
      analyses adjusting for traditional cardiovascular risk factors, each 1-SD
      increase in colony-forming units was associated with a ~16% decrease in coronary
      artery calcification (P=0.02) and 17% decrease in abdominal aortic calcification
      (P=0.03). In contrast, neither CD34(+)/KDR(+) nor CD34(+) variation was
      associated with significant differences in coronary or aortic calcification.
      CONCLUSIONS: In this large, community-based sample of men and women, lower colony
      forming unit number was associated with a higher burden of subclinical
      atherosclerosis in the coronary arteries and aorta. Decreased angiogenic
      potential could contribute to the development of atherosclerosis in humans.

PMID- 20823387
TI  - Scimitar syndrome: a European Congenital Heart Surgeons Association (ECHSA)
      multicentric study.
AB  - BACKGROUND: Scimitar syndrome is a rare congenital heart disease. To evaluate the
      surgical results, we embarked on the European Congenital Heart Surgeons
      Association (ECHSA) multicentric study. METHODS AND RESULTS: From January 1997 to
      December 2007, we collected data on 68 patients who underwent surgery for
      scimitar syndrome. Primary outcomes included hospital mortality and the efficacy
      of repair at follow-up. Median age at surgery was 1.4 years (interquartile range,
      0.46 to 7.92 years). Forty-four patients (64%) presented with symptoms. Surgical
      repair included intraatrial baffle in 38 patients (56%; group 1) and
      reimplantation of the scimitar vein onto the left atrium in 21 patients (31%;
      group 2). Eight patients underwent right pneumectomy, and 1 had a right lower
      lobe lobectomy (group 3). Four patients died in hospital (5.9%; 1 patient in
      group 1, 2.6%; 3 patients in group 3, 33%). Median follow-up time was 4.5 years.
      There were 2 late deaths (3.1%) resulting from severe pulmonary arterial
      hypertension. Freedom from scimitar drainage stenosis at 13 years was 83.8% in
      group 1 and 85.8% in group 2. Four patients in group 1 were reoperated, and 3
      patients (2 in group 1 [6%] and 1 in group 2 [4.8%]) required balloon
      dilation/stenting for scimitar drainage stenosis. CONCLUSIONS: The surgical
      treatment of this rare syndrome is safe and effective. The majority of patients
      were asymptomatic at the follow-up control. There were a relatively high
      incidence of residual scimitar drainage stenosis that is similar between the 2
      reported corrective surgical techniques used.

PMID- 20823388
TI  - Attained educational level and incident atherothrombotic events in low- and
      middle-income compared with high-income countries.
AB  - BACKGROUND: Studies report a protective effect of higher attained educational
      level (AEL) on cardiovascular outcomes. However, most of these studies have been
      conducted in high-income countries (HICs) and lack representation from low- and
      middle-income countries (LMICs), which bear >80% of the global burden of
      cardiovascular disease. METHODS AND RESULTS: The Reduction of Atherothrombosis
      for Continued Health (REACH) Registry is a prospective study of 67 888 subjects
      with either established atherothrombotic (coronary, cerebrovascular, and/or
      peripheral arterial) disease or multiple atherothrombotic risk factors enrolled
      from 5587 physician practices in 44 countries. At baseline, AEL (0 to 8 years, 9
      to 12 years, trade or technical school, and university) was self-reported for 61
      332 subjects. Outcomes included the baseline prevalence of atherothrombotic risk
      factors and the rate of incident cardiovascular events (cardiovascular death,
      nonfatal myocardial infarction, or nonfatal stroke) through 23 months across AEL
      groups, stratified by sex and world region (LMICs or HICs). Educational
      attainment was inversely associated with age and diabetes mellitus and directly
      associated with hypercholesterolemia in all subjects. However, for other risk
      factors such as obesity, smoking, hypertension, and baseline burden of vascular
      disease, AEL was protective (inversely associated) in HICs but not protective in
      LMICs. The protective effect of greater AEL on incident cardiovascular events was
      strongest in men from HICs (P<0.0001), more modest in women from HICs (P=0.0026)
      and in men from LMICs (P=0.082), and essentially absent in women from LMICs
      (P=0.32). CONCLUSION: In contrast to HICs, higher AEL may not be protective
      against cardiovascular events in LMICs, particularly in women.

PMID- 20823389
TI  - Prophylactic implantable defibrillator in patients with arrhythmogenic right
      ventricular cardiomyopathy/dysplasia and no prior ventricular fibrillation or
      sustained ventricular tachycardia.
AB  - BACKGROUND: The role of implantable cardioverter-defibrillator (ICD) in patients
      with arrhythmogenic right ventricular cardiomyopathy/dysplasia and no prior
      ventricular fibrillation (VF) or sustained ventricular tachycardia is an unsolved
      issue. METHODS AND RESULTS: We studied 106 consecutive patients (62 men and 44
      women; age, 35.6+/-18 years) with arrhythmogenic right ventricular
      cardiomyopathy/dysplasia who received an ICD based on 1 or more arrhythmic risk
      factors such as syncope, nonsustained ventricular tachycardia, familial sudden
      death, and inducibility at programmed ventricular stimulation. During follow-up
      of 58+/-35 months, 25 patients (24%) had appropriate ICD interventions and 17
      (16%) had shocks for life-threatening VF or ventricular flutter. At 48 months,
      the actual survival rate was 100% compared with the VF/ventricular flutter-free
      survival rate of 77% (log-rank P=0.01). Syncope significantly predicted any
      appropriate ICD interventions (hazard ratio, 2.94; 95% confidence interval, 1.83
      to 4.67; P=0.013) and shocks for VF/ventricular flutter (hazard ratio, 3.16; 95%
      confidence interval, 1.39 to 5.63; P=0.005). The positive predictive value of
      programmed ventricular stimulation was 35% for any appropriate ICD intervention
      and 20% for shocks for VF/ventricular flutter, with a negative predictive value
      of 70% and 74%. None of the 27 asymptomatic patients with isolated familial
      sudden death had appropriate ICD therapy. Twenty patients (19%) had inappropriate
      ICD interventions, and 18 (17%) had device-related complications. CONCLUSIONS:
      One fourth of patients with arrhythmogenic right ventricular
      cardiomyopathy/dysplasia and no prior sustained ventricular tachycardia or VF had
      appropriate ICD interventions. Syncope was an important predictor of life-saving
      ICD intervention and is an indication for ICD. Prophylactic ICD may not be
      indicated in asymptomatic patients because of their low arrhythmic risk
      regardless of familial sudden death and programmed ventricular stimulation
      findings. Programmed ventricular stimulation had a low predictive accuracy for
      ICD therapy.

PMID- 20823390
TI  - Spectrum and outcome of reoperations after the Ross procedure.
AB  - BACKGROUND: Proposed advantages to the Ross procedure included presumed increased
      freedom from reoperation and simpler reoperation for pulmonary conduit
      replacement if needed. It is increasingly apparent, however, that reoperations
      are frequent after the Ross procedure and that when required, they may be more
      complex than previously thought. METHODS AND RESULTS: Between September 1991 and
      August 2008, 56 patients underwent reoperation at our institution after a Ross
      procedure performed by ourselves (n=13) or elsewhere (n=43). Median age at first
      reoperation at our institution was 26 years (range 1 to 69 years). The 4 most
      common indications for reoperation were isolated autograft (neoaortic)
      regurgitation in 11 cases (20), isolated pulmonary conduit regurgitation/stenosis
      in 9 (16), combined autograft regurgitation/dilatation in 8 (14), and combined
      autograft regurgitation and pulmonary conduit regurgitation/stenosis in 6 (11). A
      total of 144 procedures were performed in these 56 patients during first
      reoperation at our institution. The autograft valve required replacement in 21
      cases (38) and aortic root replacement in 21 (38), with ascending aortic/arch
      reconstruction in 13 (23) and mitral valve surgery in 5 (9). The pulmonary valve
      was replaced in 33 cases (59) and the tricuspid valve was repaired/replaced in 10
      (18). Early mortality was 1.8 (1 of 56 patients), and morbidity included 6
      patients with respiratory failure and 3 who required postcardiotomy
      extracorporeal membrane oxygenation. There were 4 late deaths during the median
      follow-up of 8 months (range 1 to 179 months). CONCLUSIONS: A broad spectrum of
      complex reoperations may be required after the Ross procedure. Patients and
      family members considering the procedure should be informed of the potential for
      associated morbidity should reoperation be necessary.

PMID- 20823392
TI  - Very long-term (15 to 20 years) clinical and angiographic outcome after coronary
      bare metal stent implantation.
AB  - BACKGROUND: We previously reported that the long-term luminal response after
      coronary bare metal stenting is triphasic, with an early restenosis phase
      spanning the 6 months after the index procedure, an intermediate-term regression
      phase from 6 months to 3 years, and a late renarrowing phase beyond 4 years.
      However, the clinical significance of late luminal renarrowing remains unknown.
      METHODS AND RESULTS: Angiographic and clinical follow-up of the same cohort of
      405 patients with successful Palmaz-Schatz stent placement was extended beyond 15
      years. Clinical follow-up was completed in 98% of patients at 5 years and in 81%
      at 15 years. The incidence of death and cardiac death at 15 years was 45.4% and
      20.6%, respectively. Paired long-term (4 to 10 years) and very long-term (>10
      years) angiographic studies without intercurrent target lesion revascularization
      were performed in 55 lesions, and minimal luminal diameter further decreased from
      1.88+/-0.50 mm to 1.60+/-0.73 mm (P=0.002). Late target lesion revascularization
      after initial stabilization of the stented segments occurred rarely within 4
      years. Beyond 4 years, however, the incidence of late target lesion
      revascularization increased steadily from 3.3% at 4 years to 24.7% at 15 years.
      The incidence of definite very late stent thrombosis was low (1.5% at 15 years).
      CONCLUSIONS: Luminal renarrowing of the stented segment beyond 4 years was a
      progressive process extending beyond 10 years. The angiographic observation of
      late in-stent restenosis was clinically relevant because a corresponding
      progressive increase in the incidence of late target lesion revascularization was
      observed beyond 4 years and up to 15 to 20 years after bare metal stent
      implantation.

PMID- 20823393
TI  - Cytochrome 2C19 polymorphism and response to adjunctive cilostazol versus high
      maintenance-dose clopidogrel in patients undergoing percutaneous coronary
      intervention.
AB  - BACKGROUND: Among patients treated with clopidogrel, carriers of the cytochrome
      P450 (CYP) 2C19 loss-of-function allele have shown increased platelet reactivity
      and higher rates of ischemic events. Although adjunctive cilostazol to dual
      antiplatelet therapy (or "triple antiplatelet therapy") intensifies platelet
      inhibition, it remains unknown whether triple antiplatelet therapy after
      percutaneous coronary intervention can achieve adequate platelet inhibition in
      patients with the CYP2C19 mutant allele. METHODS AND RESULTS: CYP2C19 genotyping
      for *1, *2, and *3 was performed in 134 high-risk patients undergoing elective
      percutaneous coronary intervention. After measurement of preprocedural platelet
      reactivity, patients were randomly assigned to receive either adjunctive
      cilostazol 100 mg twice daily (triple group; n=69) or high maintenance-dose (MD)
      clopidogrel of 150 mg daily (high-MD group; n=65). Using light transmittance
      aggregometry and the VerifyNow P2Y(12) assay, platelet reactivity was assessed
      before the index procedure and at 30-day follow-up. The primary end point was
      absolute change in maximal platelet aggregation (DeltaAgg(max)) according to
      CYP2C19 genotyping. High posttreatment platelet reactivity was defined as 5
      MUmol/L ADP-induced maximal platelet aggregation >50%. In noncarriers of the
      CYP2C19*2/*3 mutant allele, DeltaAgg(max) values after 5 and 20 MUmol/L ADP
      stimuli did not differ significantly between the triple (n=22) versus the high-MD
      group (n=22) (23.6+/-21.6% versus 16.6+/-15.4%, P=0.224 and 26.4+/-22.2% versus
      18.6+/-14.9%, P=0.174, respectively). Absolute changes in late platelet
      aggregation and P2Y(12) reaction unit were not different between the groups. The
      rate of high posttreatment platelet reactivity at 30-day follow-up also was
      comparable between the triple versus the high-MD group (4.5% versus 13.6%,
      P=0.607). In carriers of at least 1 CYP2C19*2/*3 mutant allele, the triple group
      (n=47) showed greater values of DeltaAgg(max) after addition of 5 MUmol/L (25.8+/
      16.8% versus 11.1+/-19.8%, P<0.001) and 20 MUmol/L ADP (26.3+/-16.0% versus
      11.5+/-16.3%, P<0.001) compared with the high-MD group (n=43). Likewise, absolute
      changes in late platelet aggregation and P2Y(12) reaction unit were consistently
      greater in the triple versus the high-MD group. Fewer patients in the triple
      group met the criteria of high posttreatment platelet reactivity at 30-day follow
      up compared with the high-MD group (6.4% versus 37.2%, P<0.001). CONCLUSIONS:
      Among high-risk patients undergoing elective percutaneous coronary intervention,
      adjunctive cilostazol can achieve consistently intensified platelet inhibition
      and reduce the risk of high posttreatment platelet reactivity irrespective of
      CYP2C19 genotyping. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01012193.

PMID- 20823394
TI  - Late vascular responses from 2 to 4 years after implantation of sirolimus-eluting
      stents: serial observations by intracoronary optical coherence tomography.
AB  - BACKGROUND: Late vascular responses after implantation of drug-eluting stents may
      play a key role in steadily increasing occurrence of very late stent thrombosis
      have not yet been fully investigated in human beings. METHODS AND RESULTS: Serial
      optical coherence tomography observations at 2 and 4 years were collected for 17
      patients treated with 21 sirolimus-eluting stents. Corresponding 376 cross
      sections within single-stent segments at intervals of 1 mm were selected for
      analyses, and neointimal thickness on each strut was measured. Extrastent lumen
      (ESL) was defined as an external lumen of the stent. Area and angle of ESL were
      measured. A total of 3369 and 3221 struts were identified at 2 and 4 years,
      respectively. From 2 to 4 years, mean neointimal thickness increased (76.8+/-75.6
      MUm versus 123.0+/-102.5 MUm; P<0.0001), whereas frequency of patients with
      uncovered struts decreased (88% versus 29%; P=0.002). Although prevalence of
      patients that had ESL was similar (59% of 2 years versus 65% of 4 years; P=1.0),
      the cross sections with ESL increased (9.6% versus 15.2%; P=0.02). Moreover, area
      and angle of ESL increased from 2 to 4 years (0.28+/-0.27 mm(2) versus 0.62+/
      0.68 mm(2) and 16.6+/-5.4 degrees  versus 65.1+/-38.4 degrees ; P<0.01,
      respectively). The incidence of subclinical thrombus did not decrease (24% at 2
      years versus 29% at 4 years; P=1.0). All thrombi were identified in patients who
      had cross sections with ESL. CONCLUSIONS: The current serial optical coherence
      tomography study showed an augmentation of neointimal growth at the late phase of
      sirolimus-eluting stent implantation. ESL may contribute to thrombus formation
      and ESL of sirolimus-eluting stents expanded from 2 to 4 years.

PMID- 20823395
TI  - Thrombotic occlusion of giant circumflex artery aneurysm after ligation of
      arteriovenous fistula.

PMID- 20823391
TI  - Multicenter cluster-randomized trial of a multifactorial intervention to improve
      antihypertensive medication adherence and blood pressure control among patients
      at high cardiovascular risk (the COM99 study).
AB  - BACKGROUND: Medication nonadherence is common and results in preventable disease
      complications. This study assessed the effectiveness of a multifactorial
      intervention to improve both medication adherence and blood pressure control and
      to reduce cardiovascular events. METHODS AND RESULTS: In this multicenter,
      cluster-randomized trial, physicians from hospital-based hypertension clinics and
      primary care centers across Spain were randomized to receive and provide the
      intervention to their high-risk patients. Eligible patients were >= 50 years of
      age, had uncontrolled hypertension, and had an estimated 10-year cardiovascular
      risk greater than 30%. Physicians randomized to the intervention group counted
      patients' pills, designated a family member to support adherence behavior, and
      provided educational information to patients. The primary outcome was blood
      pressure control at 6 months. Secondary outcomes included both medication
      adherence and a composite end point of all-cause mortality and cardiovascular
      related hospitalizations. Seventy-nine physicians and 877 patients participated
      in the trial. The mean duration of follow-up was 39 months. Intervention patients
      were less likely to have an uncontrolled systolic blood pressure (odds ratio
      0.62, 95% confidence interval 0.50 to 0.78) and were more likely to be adherent
      (odds ratio 1.91, 95% confidence interval 1.19 to 3.05) than control group
      patients at 6 months. After 5 years, 16% of the patients in the intervention
      group and 19% in the control group met the composite end point (hazard ratio
      0.97, 95% confidence interval 0.67 to 1.39). CONCLUSIONS: A multifactorial
      intervention to improve adherence to antihypertensive medication was effective in
      improving both adherence and blood pressure control, but it did not appear to
      improve long-term cardiovascular events.

PMID- 20823396
TI  - Letter by Antonelli Incalzi et al regarding article, "endogenous erythropoietin
      and outcome in heart failure".

PMID- 20823398
TI  - Cardiac resynchronization therapy in patients with New York Heart Association
      class I and II heart failure: an approach to 2010.

PMID- 20823399
TI  - In vivo histological assessment of a spontaneous coronary artery dissection.

PMID- 20823400
TI  - Looking ahead to the past.

PMID- 20823401
TI  - Receptor tyrosine kinase transmembrane domain interactions: potential target for
      "interceptor" therapy.
AB  - Signaling by receptor tyrosine kinases (RTKs) involves ligand-induced
      dimerization of receptors within the plasma membrane, triggering subsequent
      downstream signaling events. Although the transmembrane domains play an important
      role in dimerization, the importance of their interactions in transmembrane
      signaling is not clearly understood. Here, I highlight recent research that
      describes the intrinsic propensity of the single transmembrane domains of all 58
      human RTKs to self-interact and suggest that these interactions could be
      exploited for designing peptides to inhibit signaling through these receptors.
      Such "interceptor" peptides would be potentially valuable as therapeutic tools
      for treating disease symptoms caused by excessive or ectopic RTK signaling.

PMID- 20823402
TI  - NF-kappaB: much learned, much to learn.
AB  - Although NF-kappaB (nuclear factor kappaB) was discovered less than 25 years ago,
      it is one of the most well-studied transcription factors. It plays critical roles
      in various immune and cellular processes, and its dysregulation is a major driver
      of cancer and inflammatory pathology. A new book published by Cold Spring Harbor
      Laboratory Press, NF-kappaB: A Network Hub Controlling Immunity, Inflammation,
      and Cancer, provides a series of excellent reviews on the architecture,
      regulation, and pathophysiological roles of NF-kappaB signaling by some of the
      leading investigators in the field.

PMID- 20823404
TI  - The great imitator: systemic nocardiosis mimicking Richter's transformation in
      relapsed chronic lymphocytic leukemia.

PMID- 20823405
TI  - Thyroid carcinosarcoma in a patient with lung carcinoma.

PMID- 20823407
TI  - Gastroduodenal ulcerations as a delayed complication of hepatic metastasis
      radioembolization.

PMID- 20823406
TI  - Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus
      dexamethasone as induction treatment prior to autologous stem-cell
      transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01
      phase III trial.
AB  - PURPOSE: To compare efficacy and safety of bortezomib plus dexamethasone and
      vincristine plus doxorubicin plus dexamethasone (VAD) as induction before stem
      cell transplantation in previously untreated myeloma. PATIENTS AND METHODS: Four
      hundred eighty-two patients were randomly assigned to VAD (n = 121), VAD plus
      dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) consolidation (n
      = 121), bortezomib plus dexamethasone (n = 121), or bortezomib plus dexamethasone
      plus DCEP (n = 119), followed by autologous stem-cell transplantation. Patients
      not achieving very good partial response (VGPR) required a second
      transplantation. The primary end point was postinduction complete response/near
      complete response (CR/nCR) rate. RESULTS: Postinduction CR/nCR (14.8% v 6.4%), at
      least VGPR (37.7% v 15.1%), and overall response (78.5% v 62.8%) rates were
      significantly higher with bortezomib plus dexamethasone versus VAD; CR/nCR and at
      least VGPR rates were higher regardless of disease stage or adverse cytogenetic
      abnormalities. Response rates were similar in patients who did and did not
      receive DCEP. Post first transplantation, CR/nCR (35.0% v 18.4%) and at least
      VGPR (54.3% v 37.2%) rates remained significantly higher with bortezomib plus
      dexamethasone. Median progression-free survival (PFS) was 36.0 months versus 29.7
      months (P = .064) with bortezomib plus dexamethasone versus VAD; respective 3
      year survival rates were 81.4% and 77.4% (median follow-up, 32.2 months). The
      incidence of severe adverse events appeared similar between groups, but
      hematologic toxicity and deaths related to toxicity (zero v seven) were more
      frequent with VAD. Conversely, rates of grade 2 (20.5% v 10.5%) and grades 3 to 4
      (9.2% v 2.5%) peripheral neuropathy during induction through first
      transplantation were significantly higher with bortezomib plus dexamethasone.
      CONCLUSION: Bortezomib plus dexamethasone significantly improved postinduction
      and post-transplantation CR/nCR and at least VGPR rates compared with VAD and
      resulted in a trend for longer PFS. Bortezomib plus dexamethasone should
      therefore be considered a standard of care in this setting.

PMID- 20823408
TI  - Recurrent scrotal hemangiomas during treatment with sunitinib.

PMID- 20823409
TI  - Primary cutaneous Epstein-Barr virus-associated B-cell lymphoma arising at the
      site of subcutaneous injections of methotrexate.

PMID- 20823410
TI  - Adolescent and young adult oncology training for health professionals: a position
      statement.
AB  - We outline here the essential elements of training for health care professionals
      who work with adolescent and young adult (AYA) patients with cancer. Research is
      emerging that a number of cancers manifest themselves differently in the AYA
      population, both in terms of biology and treatment response. In addition, there
      are a number of issues uniquely experienced by the AYA population that are
      critical for health care professionals working within AYA oncology (AYAO) to
      understand. The LIVESTRONG Young Adult Alliance, a Lance Armstrong Foundation
      program and a result of the Adolescent and Young Adult Oncology Progress Review
      Group cosponsored by the Lance Armstrong Foundation and the National Cancer
      Institute, assembled a group of experts representing relevant medical,
      psychosocial, and advocacy disciplines to create a blueprint for the training and
      development of health care professionals caring for AYA patients with cancer. The
      Alliance recommends that all health care professionals working in AYAO receive
      training that provides expertise in the following three critical areas: AYA
      specific medical knowledge; care delivery specific to AYAs relative to pediatric
      and older adult populations; and competency in application and delivery of AYA
      specific practical knowledge. These three areas should form the foundation for
      curricula and programs designed to train health care professionals caring for
      AYAO patients.

PMID- 20823412
TI  - Miliary brain metastases in lung cancer.

PMID- 20823411
TI  - Survival benefit with proapoptotic molecular and pathologic responses from dual
      targeting of mammalian target of rapamycin and epidermal growth factor receptor
      in a preclinical model of pancreatic neuroendocrine carcinogenesis.
AB  - PURPOSE: Pancreatic neuroendocrine tumors (PNETs), although rare, often
      metastasize, such that surgery, the only potentially curative therapy, is not
      possible. There is no effective systemic therapy for patients with advanced
      PNETs. Therefore, new strategies are needed. Toward that end, we investigated the
      potential benefit of dual therapeutic targeting of the epidermal growth factor
      receptor (EGFR) and mammalian target of rapamycin (mTOR) kinases, using a
      preclinical mouse model of PNET. MATERIALS AND METHODS: Rapamycin and erlotinib,
      inhibitors of mTOR and EGFR, respectively, were used to treat RIP-Tag2 transgenic
      mice bearing advanced multifocal PNET. Tumor growth and survival were monitored,
      and tumors were surveyed for potential biomarkers of response to the
      therapeutics. RESULTS: Rapamycin monotherapy was notably efficacious, prolonging
      survival concomitant with tumor stasis (stable disease). However, the tumors
      developed resistance, as evidenced by eventual relapse to progressive tumor
      growth. Erlotinib monotherapy slowed tumor growth and elicited a marginal
      survival benefit. In combination, there was an unprecedented survival benefit in
      the face of this aggressive multifocal cancer and, in contrast to either
      monotherapy, the development of adaptive resistance was not apparent.
      Additionally, the antiapoptotic protein survivin was implicated as a biomarker of
      sensitivity and beneficial responses to the dual targeted therapy. CONCLUSION:
      Preclinical trials in a mouse model of endogenous PNET suggest that combined
      targeting of the mTOR and EGFR signaling pathways could have potential clinical
      benefit in treating PNET. These results have encouraged development of an ongoing
      phase II clinical trial aimed to evaluate the efficacy of this treatment regimen
      in human neuroendocrine tumors.

PMID- 20823413
TI  - Small tumors, intermediate models, big hopes.

PMID- 20823414
TI  - Renal cell carcinoma with t(6;11) translocation: a patient case with a novel
      Alpha-TFEB fusion point.

PMID- 20823415
TI  - Non-small-cell lung cancer mRNA expression signature predicting response to
      adjuvant chemotherapy.

PMID- 20823416
TI  - Patient with HIV-associated plasmablastic lymphoma responding to bortezomib alone
      and in combination with dexamethasone, gemcitabine, oxaliplatin, cytarabine, and
      pegfilgrastim chemotherapy and lenalidomide alone.

PMID- 20823417
TI  - Medulloblastoma comprises four distinct molecular variants.
AB  - PURPOSE: Recent genomic approaches have suggested the existence of multiple
      distinct subtypes of medulloblastoma. We studied a large cohort of
      medulloblastomas to determine how many subgroups of the disease exist, how they
      differ, and the extent of overlap between subgroups. METHODS: We determined gene
      expression profiles and DNA copy number aberrations for 103 primary
      medulloblastomas. Bioinformatic tools were used for class discovery of
      medulloblastoma subgroups based on the most informative genes in the data set.
      Immunohistochemistry for subgroup-specific signature genes was used to determine
      subgroup affiliation for 294 nonoverlapping medulloblastomas on two independent
      tissue microarrays. RESULTS: Multiple unsupervised analyses of transcriptional
      profiles identified the following four distinct, nonoverlapping molecular
      variants: WNT, SHH, group C, and group D. Supervised analysis of these four
      subgroups revealed significant subgroup-specific demographics, histology,
      metastatic status, and DNA copy number aberrations. Immunohistochemistry for DKK1
      (WNT), SFRP1 (SHH), NPR3 (group C), and KCNA1 (group D) could reliably and
      uniquely classify formalin-fixed medulloblastomas in approximately 98% of
      patients. Group C patients (NPR3-positive tumors) exhibited a significantly
      diminished progression-free and overall survival irrespective of their metastatic
      status. CONCLUSION: Our integrative genomics approach to a large cohort of
      medulloblastomas has identified four disparate subgroups with distinct
      demographics, clinical presentation, transcriptional profiles, genetic
      abnormalities, and clinical outcome. Medulloblastomas can be reliably assigned to
      subgroups through immunohistochemistry, thereby making medulloblastoma
      subclassification widely available. Future research on medulloblastoma and the
      development of clinical trials should take into consideration these four distinct
      types of medulloblastoma.

PMID- 20823418
TI  - Favorable response to gefitinib treatment of lung adenocarcinoma with coexisting
      germline and somatic epidermal growth factor receptor mutations.

PMID- 20823419
TI  - Non-Sentinel Node Risk Score (N-SNORE): a scoring system for accurately
      stratifying risk of non-sentinel node positivity in patients with cutaneous
      melanoma with positive sentinel lymph nodes.
AB  - PURPOSE: Sentinel node (SN) biopsy allows identification of patients with
      melanoma at risk of further metastatic disease in regional non-sentinel nodes
      (NSN). We investigated clinicopathologic factors that predict NSN positivity in
      an attempt to identify patients who may be safely spared completion lymph node
      dissection (CLND). PATIENTS AND METHODS: Clinicopathologic factors previously
      shown to be predictive of NSN positivity were analyzed in 409 patients with SN
      positive disease (309 of whom underwent CLND) managed at a single melanoma
      center. A weighted score Non-Sentinel Node Risk Score [N-SNORE] incorporating
      predictive factors was derived, and the efficacy of N-SNORE at stratifying risk
      of NSN involvement was studied. RESULTS: Factors independently predictive of NSN
      positivity included primary tumor regression, proportion of harvested SNs
      involved by melanoma (%PosSN), sex (trend), and SN tumor burden indices (maximum
      size of largest deposit [MaxSize], % cross-sectional area of SN occupied by
      tumor, tumor penetrative depth, intranodal location of tumor) and perinodal
      lymphatic invasion (PLI). Of SN tumor burden criteria, MaxSize was the strongest
      predictor. N-SNORE was the sum of scores for five parameters: sex (female = 0,
      male = 1), regression (absent = 0, present = 2), %PosSN (absent = 0, present =
      2), MaxSize (<= 0.5 mm = 0, 0.51 to 2.00 mm = 1, 2.01 to 10.00 mm = 2, > 10.00 mm
      = 3), and PLI (absent = 0, present = 3). N-SNOREs of 0, 1 to 3, 4 to 5, 6 to 7,
      and >= 8 were associated with very low (0%), low (5% to 10%), intermediate (15%
      to 20%), high (40% to 50%), and very high (70% to 80%) risks of NSN involvement.
      CONCLUSION: A weighted score (N-SNORE) based on clinicopathologic characteristics
      accurately stratifies risk of NSN involvement in patients with melanoma. If
      validated in future studies, N-SNORE will better predict prognosis, aid in
      management decisions, and stratify patient groups for entry into clinical trials.

PMID- 20823420
TI  - Angiosarcoma of the ovary: is it always a lethal disease?

PMID- 20823421
TI  - Avoidance of CYP2D6 inhibitors in patients receiving tamoxifen.

PMID- 20823422
TI  - Prognostic and predictive gene signature for adjuvant chemotherapy in resected
      non-small-cell lung cancer.
AB  - PURPOSE: The JBR.10 trial demonstrated benefit from adjuvant
      cisplatin/vinorelbine (ACT) in early-stage non-small-cell lung cancer (NSCLC). We
      hypothesized that expression profiling may identify stage-independent subgroups
      who might benefit from ACT. PATIENTS AND METHODS: Gene expression profiling was
      conducted on mRNA from 133 frozen JBR.10 tumor samples (62 observation [OBS], 71
      ACT). The minimum gene set that was selected for the greatest separation of good
      and poor prognosis patient subgroups in OBS patients was identified. The
      prognostic value of this gene signature was tested in four independent published
      microarray data sets and by quantitative reverse-transcriptase polymerase chain
      reaction (RT-qPCR). RESULTS: A 15-gene signature separated OBS patients into high
      risk and low-risk subgroups with significantly different survival (hazard ratio
      [HR], 15.02; 95% CI, 5.12 to 44.04; P < .001; stage I HR, 13.31; P < .001; stage
      II HR, 13.47; P < .001). The prognostic effect was verified in the same 62 OBS
      patients where gene expression was assessed by qPCR. Furthermore, it was
      validated consistently in four separate microarray data sets (total 356 stage IB
      to II patients without adjuvant treatment) and additional JBR.10 OBS patients by
      qPCR (n = 19). The signature was also predictive of improved survival after ACT
      in JBR.10 high-risk patients (HR, 0.33; 95% CI, 0.17 to 0.63; P = .0005), but not
      in low-risk patients (HR, 3.67; 95% CI, 1.22 to 11.06; P = .0133; interaction P <
      .001). Significant interaction between risk groups and ACT was verified by qPCR.
      CONCLUSION: This 15-gene expression signature is an independent prognostic marker
      in early-stage, completely resected NSCLC, and to our knowledge, is the first
      signature that has demonstrated the potential to select patients with stage IB to
      II NSCLC most likely to benefit from adjuvant chemotherapy with
      cisplatin/vinorelbine.

PMID- 20823423
TI  - Light chain-induced acute renal failure can be reversed by bortezomib-doxorubicin
      dexamethasone in multiple myeloma: results of a phase II study.
AB  - PURPOSE: To assess the efficacy of bortezomib-doxorubicin-dexamethasone (BDD)
      therapy in patients with multiple myeloma with light chain-induced acute renal
      failure. PATIENTS AND METHODS: Sixty-eight patients with light chain-induced
      acute renal failure and glomerular filtration rate (GFR) less than 50 mL/min
      received bortezomib (1.0 mg/m(2) on days 1, 4, 8, and 11), doxorubicin (9 mg/m(2)
      on days 1 and 4), and dexamethasone (40 mg on days 1, 4, 8, and 11); if well
      tolerated after two cycles, bortezomib could be increased to 1.3 mg/m(2) and
      doxorubicin administered on days 1, 4, 8, and 11. RESULTS: By intent-to-treat
      analysis a myeloma response was obtained in 72% of 18 previously and 50 not
      previously treated patients (complete response [CR]/near CR [nCR], 38%; very good
      partial response [VGPR], 15%; partial response [PR], 13%; minor response [MR],
      6%). Renal response was achieved in 62% of patients (renal CR, 31%; renal PR, 7%;
      renal MR, 24%). Median GFR increased from 20.5 to 48.4 mL/min. GFR improvement
      correlated with tumor response; the greatest increase to 59.6 mL/min was seen in
      the group of patients with CR/nCR/VGPR. Median progression-free survival was 12.1
      months. One- and 2-year survival rates were 72% and 58%, respectively. Survival
      did not differ between patients with and without renal response but was inferior
      in previously treated patients (P < .001). In multivariate analysis, baseline GFR
      and tumor response correlated with renal response, and pretreatment status,
      lactate dehydrogenase, and myeloma response correlated with survival. The most
      common grade 3 or 4 toxicities were infection (19.1%), thrombocytopenia (14.7%),
      neutropenia (14.7%), fatigue/weakness (10.3%), and polyneuropathy (8.8%).
      CONCLUSION: BDD induced a high rate of myeloma and renal responses, and treatment
      was well tolerated.

PMID- 20823425
TI  - The cover. Hester Street.

PMID- 20823424
TI  - Re: Mortality from lymphohematopoietic malignancies and brain cancer among
      embalmers exposed to formaldehyde.

PMID- 20823426
TI  - A piece of my mind. The hands that guide me.

PMID- 20823427
TI  - AIDS conference: encouraging advances amid funding worries for global treatment.

PMID- 20823428
TI  - Have polio-free countries lost sight of need to keep vaccination rates high?

PMID- 20823429
TI  - From research to health care practice: how the UK uses data on comparative
      effectiveness. Interview by Bridget M. Kuehn.

PMID- 20823430
TI  - Bleeding avoidance strategies and percutaneous coronary intervention.

PMID- 20823431
TI  - Guidelines for glycemic control and individualized targets.

PMID- 20823432
TI  - Pediatric mortality due to inborn errors of metabolism in Victoria, Australia: a
      population-based study.

PMID- 20823435
TI  - Clinical characteristics and 30-day outcomes for influenza A 2009 (H1N1), 2008
      2009 (H1N1), and 2007-2008 (H3N2) infections.
AB  - CONTEXT: The clinical characteristics of pandemic 2009 influenza A(H1N1)
      infections have not been compared directly with illnesses caused by other
      influenza A strains. OBJECTIVE: To compare clinical features and outcomes for
      2009 H1N1, seasonal H1N1, and H3N2 influenza in a population-based cohort.
      DESIGN, SETTING, AND PARTICIPANTS: Active surveillance with 30-day follow-up for
      influenza cases among children and adults living in a 14-zip code area in
      Wisconsin. Patients with subjective fever, chills, or cough of fewer than 8 days'
      duration were screened for eligibility during an outpatient or inpatient
      encounter. Consenting patients were interviewed and tested for influenza A during
      the 2007-2008 and 2008-2009 influenza seasons and from May to November 2009; 6874
      patients (70%-86% of eligible patients) agreed to participate. Medical records
      were reviewed to assess outcomes. MAIN OUTCOME MEASURES: Hospital admission,
      radiographically confirmed pneumonia, and clinical characteristics of influenza A
      by strain. RESULTS: We identified 545 2009 H1N1, 221 seasonal H1N1, and 632 H3N2
      infections. The median ages of infected participants were 10, 11, and 25 years,
      respectively (P < .001). Hospital admission occurred within 30 days for 6 of 395
      children with 2009 H1N1 (1.5%; 95% confidence interval [CI], 0.6%-3.1%), 5 of 135
      with seasonal H1N1 (3.7%; 95% CI, 1.4%-8.0%), and 8 of 255 with H3N2 (3.1%; 95%
      CI, 1.5%-5.9%). Among adults, hospital admission occurred in 6 of 150 with 2009
      H1N1 (4.0%; 95% CI, 1.6%-8.1%), 2 of 86 with seasonal H1N1 (2.3%; 95% CI, 0.3%
      8.1%), and 17 of 377 with H3N2 (4.5%; 95% CI, 2.7%-7.0%). Pneumonia occurred in
      10 children with 2009 H1N1 (2.5%; 95% CI, 1.3%-4.5%), 2 with seasonal H1N1 (1.5%;
      95% CI, 0.2%-5.2%), and 5 with H3N2 (2.0%; 95% CI, 0.7%-4.3%). Among adults,
      pneumonia occurred in 6 with 2009 H1N1 (4.0%; 95% CI, 1.6%-8.1%), 2 with seasonal
      H1N1 (2.3%; 95% CI, 0.3%-8.1%), and 4 with H3N2 (1.1%; 95% CI, 0.3%-2.7%).
      CONCLUSIONS: In this population, individuals with 2009 H1N1 infection were
      younger than those with H3N2. The risk of most serious complications was not
      elevated in adults or children with 2009 H1N1 compared with recent seasonal
      strains.

PMID- 20823434
TI  - Reuse of nevirapine in exposed HIV-infected children after protease inhibitor
      based viral suppression: a randomized controlled trial.
AB  - CONTEXT: Protease inhibitor (PI)-based therapy is recommended for infants
      infected with human immunodeficiency virus (HIV) who were exposed to nevirapine
      for prevention of mother-to-child HIV transmission. However, there are
      limitations of continuing PI-based therapy indefinitely and reuse of nevirapine
      has many advantages. OBJECTIVE: To test whether nevirapine-exposed infants who
      initially achieve viral suppression with PI-based therapy can maintain viral
      suppression when switched to nevirapine-based therapy. DESIGN, SETTING, AND
      PATIENTS: Randomized trial conducted between April 2005 and May 2009 at a
      hospital in Johannesburg, South Africa, among 195 children who achieved viral
      suppression less than 400 copies/mL for 3 or more months from a cohort of 323
      nevirapine-exposed children who initiated PI-based therapy before 24 months of
      age. INTERVENTIONS: Control group children continued to receive ritonavir-boosted
      lopinavir, stavudine, and lamivudine (n = 99). Switch group children substituted
      nevirapine for ritonavir-boosted lopinavir (n = 96). MAIN OUTCOME MEASURES:
      Children were followed up for 52 weeks after randomization. Plasma HIV-1 RNA of
      greater than 50 copies/mL was the primary end point. Confirmed viremia greater
      than 1000 copies/mL was used as a criterion to consider regimen changes for
      children in either group (safety end point). RESULTS: Plasma viremia greater than
      50 copies/mL occurred less frequently in the switch group (Kaplan-Meier
      probability, 0.438; 95% CI, 0.334-0.537) than in the control group (0.576; 95%
      CI, 0.470-0.668) (P = .02). Confirmed viremia greater than 1000 copies/mL
      occurred more frequently in the switch group (0.201; 95% CI, 0.125-0.289) than in
      the control group (0.022; 95% CI, 0.004-0.069) (P < .001). CD4 cell response was
      better in the switch group (median CD4 percentage at 52 weeks, 34.7) vs the
      control group (CD4 percentage, 31.3) (P = .004). Older age (relative hazard [RH],
      1.71; 95% CI, 1.08-2.72) was associated with viremia greater than 50 copies/mL in
      the control group. Inadequate adherence (RH, 4.14; 95% CI, 1.18-14.57) and drug
      resistance (RH, 4.04; 95% CI, 1.40-11.65) before treatment were associated with
      confirmed viremia greater than 1000 copies/mL in the switch group. CONCLUSION:
      Among HIV-infected children previously exposed to nevirapine, switching to
      nevirapine-based therapy after achieving viral suppression with a ritonavir
      boosted lopinavir regimen resulted in lower rates of viremia greater than 50
      copies/mL than maintaining the primary ritonavir-boosted lopinavir regimen. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00117728.

PMID- 20823436
TI  - Pneumococcal conjugate vaccination and nasopharyngeal acquisition of pneumococcal
      serotype 19A strains.
AB  - CONTEXT: The rapid increase in multiresistant serotype 19A as a cause of invasive
      and respiratory pneumococcal disease has been associated in time with the
      widespread implementation of 7-valent pneumococcal conjugate vaccination (PCV-7)
      in several countries. Because spontaneous fluctuations in time and antibiotic
      selective pressure may have induced this serotype 19A increase, controlled
      studies are needed to assess the role of PCV-7. OBJECTIVE: To examine the
      association of PCV-7 vaccination and nasopharyngeal acquisition of serotype 19A
      pneumococci, their clonal distribution, and antibiotic susceptibility. DESIGN,
      SETTING, AND PATIENTS: Post hoc per-protocol completer's analysis as part of a
      randomized controlled trial of nasopharyngeal Streptococcus pneumoniae carriage
      enrolling 1003 healthy newborns with follow-up to the age of 24 months in The
      Netherlands, which has low antibiotic resistance rates. The study was conducted
      before widespread PCV-7 implementation in infants, between July 7, 2005, and
      February 14, 2008. Nasopharyngeal swabs were obtained at the age of 6 weeks and
      at 6, 12, 18, and 24 months. INTERVENTION: Infants were randomly assigned to
      receive 2 doses of PCV-7 at 2 and 4 months; 2 + 1 doses of PCV-7 at 2, 4, and 11
      months; or no dosage (unvaccinated control group). MAIN OUTCOME MEASURE:
      Cumulative proportion of children with nasopharyngeal acquisition of a new
      serotype 19A strain from 6 through 24 months of age. RESULTS: Nine hundred forty
      eight children completed the study. Fifty-four nasopharyngeal serotype 19A
      carriage isolates from 318 in the 2-dose group, 66 isolates from 327 in the 2 + 1
      dose group, and 33 isolates from 303 in the unvaccinated were collected from 6
      weeks through 24 months. The cumulative proportion who tested positive for new
      nasopharyngeal serotype 19A acquisition from 6 through 24 months of age was
      significantly higher in those having received the 2 + 1-dose PCV-7 schedule
      (16.2%; 95% confidence interval [CI], 12.6%-20.6%) vs those who were unvaccinated
      (9.2%; 95% CI, 6.5%-13.0%; relative risk [RR], 1.75; 95% CI, 1.14-2.70) but not
      after a 2-dose schedule (13.2%; 95% CI, 9.9%-17.4%; RR, 1.43; 95% CI, 0.91-2.25).
      There were 28 different sequence types identified, including 6 new types. The
      proportion of children with new 19A acquisition who had used antibiotics in the
      last 6 months (18.7%) did not differ among groups. Five isolates were penicillin
      intermediate susceptible and another 3 were nonsusceptible to erythromycin and
      azithromycin, all in the vaccine groups. CONCLUSION: A 2 + 1-dose PCV-7 schedule
      was associated with an increase in serotype 19A nasopharyngeal acquisition
      compared with unvaccinated controls. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00189020.

PMID- 20823438
TI  - Public reporting of hospital hand hygiene compliance--helpful or harmful?

PMID- 20823437
TI  - Relationship between patient panel characteristics and primary care physician
      clinical performance rankings.
AB  - CONTEXT: Physicians have increasingly become the focus of clinical performance
      measurement. OBJECTIVE: To investigate the relationship between patient panel
      characteristics and relative physician clinical performance rankings within a
      large academic primary care network. DESIGN, SETTING, AND PARTICIPANTS: Cohort
      study using data from 125,303 adult patients who had visited any of the 9
      hospital-affiliated practices or 4 community health centers between January 1,
      2003, and December 31, 2005, (162 primary care physicians in 1 physician
      organization linked by a common electronic medical record system in Eastern
      Massachusetts) to determine changes in physician quality ranking based on an
      aggregate of Health Plan Employer and Data Information Set (HEDIS) measures after
      adjusting for practice site, visit frequency, and patient panel characteristics.
      MAIN OUTCOME MEASURES: Composite physician clinical performance score based on 9
      HEDIS quality measures (reported by percentile, with lower scores indicating
      higher quality). RESULTS: Patients of primary care physicians in the top quality
      performance tertile compared with patients of primary care physicians in the
      bottom quality tertile were older (51.1 years [95% confidence interval {CI}, 49.6
      52.6 years] vs 46.6 years [95% CI, 43.8-49.5 years], respectively; P < .001), had
      a higher number of comorbidities (0.91 [95% CI, 0.83-0.98] vs 0.80 [95% CI, 0.66
      0.95]; P = .008), and made more frequent primary care practice visits (71.0% [95%
      CI, 68.5%-73.5%] vs 61.8% [95% CI, 57.3%-66.3%] with >3 visits/year; P = .003).
      Top tertile primary care physicians compared with the bottom tertile physicians
      had fewer minority patients (13.7% [95% CI, 10.6%-16.7%] vs 25.6% [95% CI, 20.2%
      31.1%], respectively; P < .001), non-English-speaking patients (3.2% [95% CI,
      0.7%-5.6%] vs 10.2% [95% CI, 5.5%-14.9%]; P <.001), and patients with Medicaid
      coverage or without insurance (9.6% [95% CI, 7.5%-11.7%] vs 17.2% [95% CI, 13.5%
      21.0%]; P <.001). After accounting for practice site and visit frequency
      differences, adjusting for patient panel factors resulted in a relative mean
      change in physician rankings of 7.6 percentiles (95% CI, 6.6-8.7 percentiles) per
      primary care physician, with more than one-third (36%) of primary care physicians
      (59/162) reclassified into different quality tertiles. CONCLUSION: Among primary
      care physicians practicing within the same large academic primary care system,
      patient panels with greater proportions of underinsured, minority, and non
      English-speaking patients were associated with lower quality rankings for primary
      care physicians.

PMID- 20823439
TI  - Exclusion of genetic information from the medical record: ethical and medical
      dilemmas.

PMID- 20823433
TI  - Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine
      following pancreatic cancer resection: a randomized controlled trial.
AB  - CONTEXT: Adjuvant fluorouracil has been shown to be of benefit for patients with
      resected pancreatic cancer. Gemcitabine is known to be the most effective agent
      in advanced disease as well as an effective agent in patients with resected
      pancreatic cancer. OBJECTIVE: To determine whether fluorouracil or gemcitabine is
      superior in terms of overall survival as adjuvant treatment following resection
      of pancreatic cancer. DESIGN, SETTING, AND PATIENTS: The European Study Group for
      Pancreatic Cancer (ESPAC)-3 trial, an open-label, phase 3, randomized controlled
      trial conducted in 159 pancreatic cancer centers in Europe, Australasia, Japan,
      and Canada. Included in ESPAC-3 version 2 were 1088 patients with pancreatic
      ductal adenocarcinoma who had undergone cancer resection; patients were
      randomized between July 2000 and January 2007 and underwent at least 2 years of
      follow-up. INTERVENTIONS: Patients received either fluorouracil plus folinic acid
      (folinic acid, 20 mg/m(2), intravenous bolus injection, followed by fluorouracil,
      425 mg/m(2) intravenous bolus injection given 1-5 days every 28 days) (n = 551)
      or gemcitabine (1000 mg/m(2) intravenous infusion once a week for 3 of every 4
      weeks) (n = 537) for 6 months. MAIN OUTCOME MEASURES: Primary outcome measure was
      overall survival; secondary measures were toxicity, progression-free survival,
      and quality of life. RESULTS: Final analysis was carried out on an intention-to
      treat basis after a median of 34.2 (interquartile range, 27.1-43.4) months'
      follow-up after 753 deaths (69%). Median survival was 23.0 (95% confidence
      interval [CI], 21.1-25.0) months for patients treated with fluorouracil plus
      folinic acid and 23.6 (95% CI, 21.4-26.4) months for those treated with
      gemcitabine (chi(1)(2) = 0.7; P = .39; hazard ratio, 0.94 [95% CI, 0.81-1.08]).
      Seventy-seven patients (14%) receiving fluorouracil plus folinic acid had 97
      treatment-related serious adverse events, compared with 40 patients (7.5%)
      receiving gemcitabine, who had 52 events (P < .001). There were no significant
      differences in either progression-free survival or global quality-of-life scores
      between the treatment groups. CONCLUSION: Compared with the use of fluorouracil
      plus folinic acid, gemcitabine did not result in improved overall survival in
      patients with completely resected pancreatic cancer. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00058201.

PMID- 20823440
TI  - Do IRBs protect human research participants?

PMID- 20823441
TI  - Refinement of adjuvant therapy for pancreatic cancer.

PMID- 20823443
TI  - JAMA patient page. Pancreatic cancer.

PMID- 20823448
TI  - Chronic consumption of a high-fat/high-fructose diet renders the liver incapable
      of net hepatic glucose uptake.
AB  - The objective of this study was to assess the response of a large animal model to
      high dietary fat and fructose (HFFD). Three different metabolic assessments were
      performed during 13 wk of feeding an HFFD (n = 10) or chow control (CTR, n = 4)
      diet: oral glucose tolerance tests (OGTTs; baseline, 4 and 8 wk),
      hyperinsulinemic-euglycemic clamps (HIEGs; baseline and 10 wk) and
      hyperinsulinemic-hyperglycemic clamps (HIHGs, 13 wk). The DeltaAUC for glucose
      during the OGTTs more than doubled after 4 and 8 wk of HFFD feeding, and the
      average glucose infusion rate required to maintain euglycemia during the HIEG
      clamps decreased by ~30% after 10 wk of HFFD feeding. These changes did not occur
      in the CTR group. The HIHG clamps included experimental periods 1 (P1, 0-90 min)
      and 2 (P2, 90-180 min). During P1, somatostatin, basal intraportal glucagon, 4 *
      basal intraportal insulin, and peripheral glucose (to double the hepatic glucose
      load) were infused; during P2, glucose was also infused intraportally (4.0 mg.kg(
      1).min(-1)). Net hepatic glucose uptake during P1 and P2 was -0.4 +/- 0.1
      [output] and 0.2 +/- 0.8 mg.kg(-1).min(-1) in the HFFD group, respectively, and
      1.8 +/- 0.8 and 3.5 +/- 1.0 mg.kg(-1).min(-1) in the CTR group, respectively (P <
      0.05 vs. HFFD during P1 and P2). Glycogen synthesis through the direct pathway
      was 0.5 +/- 0.2 and 1.5 +/- 0.4 mg.kg(-1).min(-1) in the HFFD and CTR groups,
      respectively (P < 0.05 vs. HFFD). In conclusion, chronic consumption of an HFFD
      diminished the sensitivity of the liver to hormonal and glycemic cues and
      resulted in a marked impairment in NHGU and glycogen synthesis.

PMID- 20823450
TI  - Odyssey between Scylla and Charybdis through storms of carbohydrate metabolism
      and diabetes: a career retrospective.
AB  - This research perspective allows me to summarize some of my work completed over
      50 years, and it is organized in seven sections. 1) The treatment of diabetes
      concentrates on the liver and/or the periphery. We quantified hormonal and
      metabolic interactions involved in physiology and the pathogenesis of diabetes by
      developing tracer methods to separate the effects of diabetes on both. We
      collaborated in the first tracer clinical studies on insulin resistance,
      hypertriglyceridemia, and the Cori cycle. 2) Diabetes reflects insulin deficiency
      and glucagon abundance. Extrapancreatic glucagon changed the prevailing dogma and
      permitted precise exploration of the roles of insulin and glucagon in physiology
      and diabetes. 3) We established the critical role of glucagon-insulin interaction
      and the control of glucose metabolism during moderate exercise and of
      catecholamines during strenuous exercise. Deficiencies of the release and effects
      of these hormones were quantified in diabetes. We also revealed how acute and
      chronic hyperglycemia affects the expression of GLUT2 gene and protein in
      diabetes. 4) We outlined molecular and physiological mechanisms whereby exercise
      training and repetitive neurogenic stress can prevent diabetes in ZDF rats. 5) We
      and others established that the indirect effect of insulin plays an important
      role in the regulation of glucose production in dogs. We confirmed this effect in
      humans and demonstrated that in type 2 diabetes it is mainly the indirect effect.
      6) We indicated that the muscle and the liver protected against glucose changes.
      7) We described molecular mechanisms responsible for increased HPA axis in
      diabetes and for the diminished responses of HPA axis, catecholamines, and
      glucagon to hypoglycemia. We proposed a new approach to decrease the threat of
      hypoglycemia.

PMID- 20823449
TI  - Treatment with a CRH-R1 antagonist prevents stress-induced suppression of the
      central neural drive to the reproductive axis in female macaques.
AB  - In response to everyday life stress, some individuals readily develop
      reproductive dysfunction (i.e., they are stress sensitive), whereas others are
      more stress resilient. When exposed to mild combined psychosocial plus metabolic
      stress (change in social environment plus reduced diet), female cynomolgus
      monkeys can be categorized as stress sensitive (SS; they rapidly become
      anovulatory in response to stress), medium stress resilient (MSR; they slowly
      become anovulatory in response to prolonged stress), or highly stress resilient
      (HSR; they maintain normal menstrual cycles in response to stress). Previously,
      we reported that monkeys that develop abnormal menstrual cycles following
      exposure to mild combined stress (MSR + SS) have increased plasma cortisol levels
      the day they move to a novel room and start a reduced diet compared with HSR
      monkeys. In this study, we examined whether there is a similar acute effect of
      mild combined stress on the reproductive axis specifically in the combined group
      of MSR + SS animals by measuring LH pulse frequency and whether treatment with a
      CRH-R1 antagonist can prevent a stress-induced suppression of LH pulse frequency
      presumably by inhibiting activity of the HPA axis. Animals that developed
      abnormal menstrual cycles in response to stress (MSR + SS monkeys) suppressed LH
      pulse frequency in response to stress exposure. Pretreatment with 10 mg/kg iv
      antalarmin prevented the stress-induced suppression of LH secretion in these
      animals without the stress-induced increase in cortisol secretion being blocked.
      We conclude that CRH, acting via nonneuroendocrine mechanisms to regulate
      neurotransmitter systems other than the HPA axis, plays a role in causing stress
      induced reproductive impairment in stress-sensitive individuals.

PMID- 20823452
TI  - Fructose: a highly lipogenic nutrient implicated in insulin resistance, hepatic
      steatosis, and the metabolic syndrome.
AB  - As dietary exposure to fructose has increased over the past 40 years, there is
      growing concern that high fructose consumption in humans may be in part
      responsible for the rising incidence of obesity worldwide. Obesity is associated
      with a host of metabolic challenges, collectively termed the metabolic syndrome.
      Fructose is a highly lipogenic sugar that has profound metabolic effects in the
      liver and has been associated with many of the components of the metabolic
      syndrome (insulin resistance, elevated waist circumference, dyslipidemia, and
      hypertension). Recent evidence has also uncovered effects of fructose in other
      tissues, including adipose tissue, the brain, and the gastrointestinal system,
      that may provide new insight into the metabolic consequences of high-fructose
      diets. Fructose feeding has now been shown to alter gene expression patterns
      (such as peroxisome proliferator-activated receptor-gamma coactivator-1alpha/beta
      in the liver), alter satiety factors in the brain, increase inflammation,
      reactive oxygen species, and portal endotoxin concentrations via Toll-like
      receptors, and induce leptin resistance. This review highlights recent findings
      in fructose feeding studies in both human and animal models with a focus on the
      molecular and biochemical mechanisms that underlie the development of insulin
      resistance, hepatic steatosis, and the metabolic syndrome.

PMID- 20823451
TI  - Sustained activation of renal N-methyl-D-aspartate receptors decreases vitamin D
      synthesis: a possible role for glutamate on the onset of secondary HPT.
AB  - N-methyl-D-aspartate (NMDA) receptors (NMDAR) are tetrameric amino acid receptors
      that act as membrane calcium channels. The presence of the receptor has been
      detected in the principal organs responsible for calcium homeostasis (kidney,
      bone, and parathyroid gland), pointing to a possible role in mineral metabolism.
      The aim of this study was to test the effect of NMDAR activation in the kidney
      and on 1,25(OH)2D3 synthesis. We determined the presence of NMDAR subunits in HK
      2 (human kidney cells) cells and proved its functionality. NMDA treatment for 4
      days induced a decrease in 1alpha-hydroxylase levels and 1,25(OH)2D3 synthesis
      through the activation of the MAPK/ERK pathway in HK-2 cells. In vivo
      administration of NMDA for 4 days also caused a decrease in blood 1,25(OH)2D3
      levels in healthy animals and an increase in blood PTH levels. This increase in
      PTH induced a decrease in the urinary excretion of calcium and an increase in
      urinary excretion of phosphorous and sodium as well as in diuresis. Bone turnover
      markers also increased. Animals with 5/6 nephrectomy showed low levels of renal
      1alpha-hydroxylase as well as high levels of renal glutamate compared with
      healthy animals. In conclusion, NMDAR activation in the kidney causes a decrease
      in 1,25(OH)2D3 synthesis, which induces an increase on PTH synthesis and release.
      In animals with chronic kidney disease, high renal levels of glutamate could be
      involved in the downregulation of 1alpha-hydroxylase expression.

PMID- 20823453
TI  - IL-6 selectively stimulates fat metabolism in human skeletal muscle.
AB  - Interleukin (IL)-6 is chronically elevated in type 2 diabetes but also during
      exercise. However, the exact metabolic role, and hence the physiological
      significance, has not been elucidated. The objective of this study was to
      investigate the in vivo effect of recombinant human (rh) IL-6 on human fat and
      glucose metabolism and signaling of both adipose tissue and skeletal muscle.
      Eight healthy postabsorptive males were infused with either rhIL-6 or saline for
      4 h, eliciting IL-6 levels of ~40 and ~1 pg/ml, respectively. Systemic, skeletal
      muscle, and adipose tissue fat and glucose metabolism was assessed before,
      during, and 2 h after cessation of the infusion. Glucose metabolism was
      unaffected by rhIL-6. In contrast, rhIL-6 increased systemic fatty acid oxidation
      approximately twofold after 60 min, and it remained elevated even 2 h after the
      infusion. The increase in oxidation was followed by an increase in systemic
      lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with
      rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an
      increase in skeletal muscle unidirectional fatty acid and glycerol release,
      indicative of an increase in lipolysis. The increased lipolysis in muscle could
      account for the systemic changes. Skeletal muscle signaling increased after 1 h
      of rhIL-6 infusion, indicated by a fourfold increase in the phosphorylated signal
      transducer and activator of transcription (STAT) 3-to-STAT3 ratio, whereas no
      changes in phosphorylated AMP-activated protein kinase or acetyl-CoA carboxylase
      levels could be observed. Our findings suggest that an acute increase in IL-6 at
      a normophysiological level selectively stimulates lipolysis in skeletal muscle,
      whereas adipose tissue is unaffected.

PMID- 20823454
TI  - Hepatic toxicity and prognosis in hepatitis C virus-infected patients with
      diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy
      regimens: a Japanese multicenter analysis.
AB  - The influence of hepatitis C virus (HCV) infection on prognosis and hepatic
      toxicity in patients with diffuse large B-cell lymphoma in the rituximab era is
      unclear. Thus, we analyzed 553 patients, 131 of whom were HCV-positive and 422 of
      whom were HCV-negative, with DLBCL treated with rituximab, cyclophosphamide,
      doxorubicin, vincristine, and prednisone (RCHOP)-like chemotherapy. Survival
      outcomes and hepatic toxicity were compared according to HCV infection. The
      median follow-up was 31 and 32 months for patients who were HCV-positive and HCV
      negative, respectively. HCV infection was not a significant risk factor for
      prognosis (3-year progression-free survival, 69% vs 77%, P = .22; overall
      survival, 75% vs 84%, P = .07). Of 131 patients who were HCV-positive, 36 (27%)
      had severe hepatic toxicity (grade 3-4), compared with 13 of 422 (3%) patients
      who were HCV-negative. Multivariate analysis revealed that HCV infection was a
      significant risk factor for severe hepatic toxicity (hazard ratio: 14.72; 95%
      confidence interval, 6.37-34.03; P < .001). An exploratory analysis revealed that
      pretreatment transaminase was predictive of severe hepatic toxicity. HCV-RNA
      levels significantly increased during immunochemotherapy (P = .006). These
      results suggest that careful monitoring of hepatic function and viral load is
      indicated during immunochemotherapy for HCV-positive patients.

PMID- 20823455
TI  - Increased thrombosis susceptibility and altered fibrin formation in STAT5
      deficient mice.
AB  - To explore the effect(s) of growth hormone signaling on thrombosis, we studied
      signal transduction and transcription factor 5 (STAT5)-deficient mice and found
      markedly reduced survival in an in vivo thrombosis model. These findings were not
      explained by a compensatory increase in growth hormone secretion. There was a
      modest increase in the activity of several procoagulant factors, but there was no
      difference in the rate or magnitude of thrombin generation in STAT5-deficient
      mice relative to control. However, thrombin-triggered clot times were markedly
      shorter, and fibrin polymerization occurred more rapidly in plasma from STAT5
      deficient mice. Fibrinogen depletion and mixing studies indicated that the effect
      on fibrin polymerization was not due to intrinsic changes in fibrinogen, but
      resulted from changes in the concentration of a circulating plasma inhibitor.
      While thrombin-triggered clot times were significantly shorter in STAT5-deficient
      animals, reptilase-triggered clot times were unchanged. Accordingly, while the
      rate of thrombin-catalyzed release of fibrinopeptide A was similar, the release
      of fibrinopeptide B was accelerated in STAT5-deficient plasma versus control.
      Taken together, these studies demonstrated that the loss of STAT5 resulted in a
      decrease in the concentration of a plasma inhibitor affecting thrombin-triggered
      cleavage of fibrinopeptide B. This ultimately resulted in accelerated fibrin
      polymerization and greater thrombosis susceptibility in STAT5-deficient animals.

PMID- 20823456
TI  - Racial disparities in incidence and outcome in multiple myeloma: a population
      based study.
AB  - Multiple myeloma (MM) is the most common hematologic malignancy in blacks. Some
      prior studies suggest inferior survival in blacks; others suggest similar
      survival. Using the original 9 Surveillance, Epidemiology, and End Results
      registries, we conducted a large-scale population-based study including 5798
      black and 28 939 white MM patients diagnosed 1973-2005, followed through 2006.
      Age-adjusted incidence rates, disease-specific survival, and relative survival
      rates were calculated by race, age, and time period of diagnosis. Mean age at
      diagnosis was 65.8 and 69.8 years for blacks and whites, respectively (P < .001).
      Incidence among blacks was m twice that among whites; this disparity was greater
      among patients < 50 years (P = .002). Over the entire study period, disease
      specific and relative survival rates were higher in blacks than whites (P <
      .001). For whites, 5-year relative survival rates increased significantly 1973
      1993 to 1994-1998 (26.3% to 30.8%; P < .001) and 1994-1998 to 1999-2005 (30.8% to
      35.0%; P = .004). Survival improvements among blacks were smaller and
      nonsignificant (1973-1993 to 1999-2005: 31.0% to 34.1%; P = .07). We found (1) a
      younger age of onset among blacks; (2) better survival in blacks 1973-2005; and
      (3) significant survival improvement among whites over time, with smaller,
      nonsignificant change seen among blacks, possibly due to unequal access to and/or
      disparate responsiveness to novel therapies.

PMID- 20823464
TI  - Approach to the patient with persistent acromegaly after pituitary surgery.
AB  - The approach to a patient with acromegaly and persistent disease after surgery
      requires a complex diagnostic assessment. Acromegaly is a chronic and insidious
      disease that is associated with multisystem comorbidities, including
      cardiovascular disease, hypertension, sleep apnea syndrome, colon polyposis,
      arthropathy, and metabolic complications including glucose intolerance and type 2
      diabetes mellitus. Patients also have a variety of signs and symptoms, including
      headache, arthralgias, carpal tunnel syndrome, sweating, fatigue, and
      psychological issues that impact significantly on quality of life. The
      recommended approach to the evaluation of the postoperative patient includes a
      biochemical assessment, with measurement of serum IGF-I along with a glucose
      suppressed GH value, radiological assessment to determine location of residual
      tumor and presence of mass effects, a physical examination for evidence of
      skeletal and soft tissue overgrowth and related signs of acromegaly, and a
      thorough clinical assessment for the presence of comorbidities. Repeat surgery is
      indicated if there is residual tumor that is surgically accessible and there may
      be a chance for surgical cure, or if there are persistent mass effects upon the
      optic chiasm. Otherwise, medical therapy is indicated, utilizing somatostatin
      analogs, dopamine agonists, and pegvisomant, a GH receptor antagonist. Radiation
      therapy is usually relegated to situations where medical therapy is ineffective
      or poorly tolerated or where patients would prefer not to sustain the cost of
      long-term medical therapy. The choice of therapy requires close dialog among
      endocrinologists, neurosurgeons, radiation therapists, and neuroophthalmologists
      for optimal care of patients.

PMID- 20823463
TI  - Approach to the patient with an adrenal incidentaloma.
AB  - Unsuspected adrenal masses, or incidentalomas, are increasingly found with the
      widespread use of thoracic and abdominal imaging. These masses may be hormonally
      active or nonfunctional and malignant or benign. Clinicians must determine the
      nature of the mass to decide what treatment, if any, is needed. Measurement of
      precontrast Hounsfield units (HU) and contrast washout on computed tomography
      scan provide useful diagnostic information. All patients should undergo
      biochemical testing for pheochromocytoma, either with plasma or urinary
      catecholamine measurements. This is particularly important before surgical
      resection, which is routinely recommended for masses larger than 4 cm in diameter
      without a clear-cut diagnosis and for others with hormonal secretion or ominous
      imaging characteristics. Hypertensive patients should undergo biochemical testing
      for hyperaldosteronism. Patients with features consistent with Cushing's
      syndrome, such as glucose intolerance, weight gain, and unexplained osteopenia,
      should be evaluated for cortisol excess. Here, the dexamethasone suppression test
      and late-night salivary cortisol may be preferred over measurement of urine
      cortisol. The ability of surgical resection to reverse features of mild
      hypercortisolism is not well established. For masses that appear to be benign
      (<10 HU; washout, >50%), small (<3 cm), and completely nonfunctioning, imaging
      and biochemical reevaluation (pheochromocytoma and hypercortisolism only) at 1-2
      yr (or more) is appropriate. For more indeterminate lesions, repeat evaluation
      for growth after 3-12 months is useful, with subsequent testing intervals based
      on the rate of growth.

PMID- 20823465
TI  - Update in serotonin and bone.
AB  - CONTEXT: Serotonin (5-HT) may be an important regulatory agent in bone, and
      agents that modify 5-HT signaling, such as selective serotonin reuptake
      inhibitors (SSRIs), are in widespread clinical use. EVIDENCE ACQUISITION:
      Evidence was obtained by PubMed search and the author's knowledge of the field.
      EVIDENCE SYNTHESIS: Recent data suggest that gut-derived 5-HT may mediate the
      skeletal effects of LDL receptor-related protein 5, stimulating intense interest
      in a novel mechanism for regulating bone mass. However, the specific biochemical
      nature of serotonergic pathways influencing bone and their direct and/or indirect
      effects on bone metabolism are still unclear. The weight of epidemiological
      evidence suggests that SSRIs are associated with reduced bone mass, increased
      bone loss, and increased risk of fractures. Interpretation of these studies is
      complicated by the confounding effects of depression, the usual indication for
      treatment with SSRIs. The mechanisms for putative SSRI-induced deleterious
      effects on the skeleton are unknown, and are likely multifactorial. CONCLUSIONS:
      5-HT may have regulatory effects on bone. Initial preclinical data suggest that
      its effects may be deleterious and may be regulated by low-density lipoprotein
      receptor-related protein 5. These studies need confirmation, as well as
      elucidation, of the biochemical pathways utilized and the feedback loops involved
      among bone, gut, and perhaps brain. Paradoxically, targeting of 5-HT synthesis
      and/or signaling in selective tissues may hold promise as an anabolic
      intervention for bone. Epidemiological data suggest that clinicians should be
      vigilant about detection of bone disease in patients who are using SSRIs.

PMID- 20823467
TI  - Clinical review: Adult height in patients with congenital adrenal hyperplasia: a
      systematic review and metaanalysis.
AB  - CONTEXT: Treatment for patients with congenital adrenal hyperplasia (CAH) may
      affect the final height of these patients. OBJECTIVE: Our objective was to
      determine the distribution of achieved height in patients with classic CAH
      diagnosed at infancy or early childhood and treated with glucocorticoids. DATA
      SOURCES: We searched MEDLINE, EMBASE, Cochrane Library, ISI Web of Science, and
      Scopus through September 2008; the reference sections of included studies; and
      expert files. STUDY SELECTION: Eligible studies included patients diagnosed with
      CAH before age 5 and followed to final height. DATA EXTRACTION: Reviewers working
      in duplicate independently extracted data on study characteristics and outcomes
      and determined each study's risk of bias. DATA SYNTHESIS: The sd score (SDS) for
      final height and corrected height (defined as final height SDS - midparental
      height SDS) were estimated from each study and pooled using random-effects
      metaanalysis. The I(2) statistic was used to assess inconsistency in results
      across studies. RESULTS: We found 35 eligible studies, most of which were
      retrospective single-cohort studies. The final height SDS achieved by CAH
      patients was -1.38 (-1.56 to -1.20; I(2) = 90.2%), and the corrected height SDS
      was -1.03 (-1.20 to -0.86; I(2) = 63.1%). This was not significantly associated
      with age at diagnosis, gender, type and dose of steroid, and age of onset of
      puberty. Mineralocorticoid users had a better height outcome in comparison with
      the nonusers (P = 0.02). CONCLUSION: Evidence derived from observational studies
      suggests that the final height of CAH patients treated with glucocorticoids is
      lower than the population norm and is lower than expected given parental height.

PMID- 20823468
TI  - Image in endocrinology. Marginal-zone lymphoma mimicking adrenal myelolipoma on
      computed tomography scan.

PMID- 20823469
TI  - Image in endocrinology. Pemberton's sign in patient with substernal goiter.

PMID- 20823470
TI  - Insulin resistance and outcomes in surgery.

PMID- 20823466
TI  - Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an
      Endocrine Society clinical practice guideline.
AB  - OBJECTIVE: We developed clinical practice guidelines for congenital adrenal
      hyperplasia (CAH). PARTICIPANTS: The Task Force included a chair, selected by The
      Endocrine Society Clinical Guidelines Subcommittee (CGS), ten additional
      clinicians experienced in treating CAH, a methodologist, and a medical writer.
      Additional experts were also consulted. The authors received no corporate funding
      or remuneration. CONSENSUS PROCESS: Consensus was guided by systematic reviews of
      evidence and discussions. The guidelines were reviewed and approved sequentially
      by The Endocrine Society's CGS and Clinical Affairs Core Committee, members
      responding to a web posting, and The Endocrine Society Council. At each stage,
      the Task Force incorporated changes in response to written comments. CONCLUSIONS:
      We recommend universal newborn screening for severe steroid 21-hydroxylase
      deficiency followed by confirmatory tests. We recommend that prenatal treatment
      of CAH continue to be regarded as experimental. The diagnosis rests on clinical
      and hormonal data; genotyping is reserved for equivocal cases and genetic
      counseling. Glucocorticoid dosage should be minimized to avoid iatrogenic
      Cushing's syndrome. Mineralocorticoids and, in infants, supplemental sodium are
      recommended in classic CAH patients. We recommend against the routine use of
      experimental therapies to promote growth and delay puberty; we suggest patients
      avoid adrenalectomy. Surgical guidelines emphasize early single-stage genital
      repair for severely virilized girls, performed by experienced surgeons.
      Clinicians should consider patients' quality of life, consulting mental health
      professionals as appropriate. At the transition to adulthood, we recommend
      monitoring for potential complications of CAH. Finally, we recommend judicious
      use of medication during pregnancy and in symptomatic patients with nonclassic
      CAH.

PMID- 20823471
TI  - 25-OH vitamin D: is it the universal panacea for metabolic syndrome and type 2
      diabetes?

PMID- 20823472
TI  - Congenital hypothyroidism: an evolving common clinical conundrum.

PMID- 20823484
TI  - A supplement on palm oil--why?

PMID- 20823485
TI  - Palm oil and health: a case of manipulated perception and misuse of science.
AB  - In the 1980s, a combination of forces came together to convince the public that
      food products containing tropical oils contributed to their risk of coronary
      heart disease. Tropical oils were competing with the U.S. soy bean oil market as
      an alternative vegetable oil, yet they were higher in saturated fat, which had
      become the target of the health promotion community for its theoretical
      association with coronary heart disease risk. Successful national campaigns were
      undertaken to force food manufacturers to remove tropical oils, including palm
      oil, from their products and to replace them with hydrogenated vegetable oils,
      resulting in increased intakes of trans-fatty acids, which later became the
      target of the same advocacy groups. Today palm oil is being touted as a suitable
      replacement for hydrogenated vegetable oils.

PMID- 20823486
TI  - The importance of the global oils and fats supply and the role that palm oil
      plays in meeting the demand for oils and fats worldwide.
AB  - This article highlights the importance of the role that palm oil plays in meeting
      the demand for oils and fats worldwide for food. On top of this food demand, the
      demand for vegetable oils for biofuels, which now absorb over 10% of world oil
      and fat supplies, has rapidly increased.

PMID- 20823487
TI  - Replacing trans fat: the argument for palm oil with a cautionary note on
      interesterification.
AB  - To replace dietary trans fatty acids (TFA), two practical options exist: revert
      to a natural saturated fat without cholesterol (most likely palm oil or its
      fractions) or move to a newer model of modified fat hardened by
      interesterification (IE). This review summarizes the relative risks for
      cardiovascular disease inherent in these options. Interestingly, both types of
      fat have been the subject of nutritional scrutiny for approximately the last 40
      years, and both have positive and negative attributes. Only during that period
      has palm oil production developed to the point where it has become the major
      edible oil in world markets, making clinical studies of it an important
      objective. On the other hand, approximately 25 human studies have fed
      interesterified fat in one form or another over this period, some for weeks, some
      as a single meal. Two types of diet designs exist. Several fed a small amount of
      interesterified fat, usually incorporated within a margarine, and stayed below
      the radar of biological detection of any abnormal metabolism. A few fed
      interesterified fat that incorporated stearic acid, as interesterified 18:0 (IE
      18:0), even comparing it to trans fat and saturated fat, as a major part of total
      daily calories to assess its metabolic impact per se. These latter 5 to 6 studies
      clearly reveal negative biological effects on lipoproteins, blood glucose,
      insulin, immune function, or liver enzymes when relatively high intake of IE-18:0
      or palmitic acid (IE-16:0) were fed in fats with sn2-saturated fatty acids. High
      intake of 18:0 in natural fats can depress total lipoproteins, while IE-18:0 and
      IE-16:0 at high levels adversely affect lipoprotein metabolism. Still other
      studies have supplied interesterified fat as a single meal or fed such fat daily
      only in a single snack, as opposed to incorporating the fat into the entire fat
      pool consumed at all meals in association with most foods (which is the more
      physiological approach and more apt to elicit effects). Even in meal studies, IE
      18:0 typically delayed fat absorption postprandially, indicating its effect on
      fat metabolism originating, in part, in the intestine. Mainly 2 saturated fatty
      acids (18:0 or 16:0) have been interesterified to harden oils, using the 16:0
      from fully hydrogenated palm oil or 18:0 from fully hydrogenated soybean oil as
      the source material. It is not clear that IE-16:0 is as problematic as IE-18:0,
      but IE-16:0 has been studied less. Levels between 8% energy (%E) and 12%E from
      18:0 as interesterified fat (the typical diet provides about 2%E-4%E as 18:0 from
      natural fats) show the most effect. Detection of adverse effects would seem to
      start around 7%E-8%E as IE-18:0, but one can assume that effects are initiated,
      even if undetected, at a lower intake, similar to the situation with TFA. Thus,
      although an intake of 1%E to 4%E from IE-18:0 does not appear to influence
      lipoproteins, it is not necessarily the only system affected. The negative
      effects of IE-18:0 may be alleviated or masked by dilution with other fats,
      especially by adding 18:2-rich polyunsaturated oils to the diet. This is similar
      to the trans fat story, i.e., if a limited intake of TFA is heavily diluted with
      other oils, the consumption of TFA fails to be detected as an adverse effect.
      Accordingly, more research is warranted to determine the appropriateness of
      interesterified fat consumption, particularly before it becomes insidiously
      embedded in the food supply similar to TFA and intake levels are achieved that
      compromise long-term health.

PMID- 20823488
TI  - Fatty acid expert roundtable: key statements about fatty acids.

PMID- 20823489
TI  - Obesity, the metabolic syndrome, and type 2 diabetes in developing countries:
      role of dietary fats and oils.
AB  - Developing countries are undergoing rapid nutrition transition concurrent with
      increases in obesity, the metabolic syndrome, and type 2 diabetes mellitus
      (T2DM). From a healthy traditional high-fiber, low-fat, low-calorie diet, a shift
      is occurring toward increasing consumption of calorie-dense foods containing
      refined carbohydrates, fats, red meats, and low fiber. Data show an increase in
      the supply of animal fats and increased intake of saturated fatty acid (SFAs)
      (obtained from coconut oil, palm oil, and ghee [clarified butter]) in many
      developing countries, particularly in South Asia and South-East Asia. In some
      South Asian populations, particularly among vegetarians, intake of n-3
      polyunsaturated fatty acids (PUFAs) (obtained from flaxseed, mustard, and canola
      oils) and long-chain (LC) n-3 PUFAs (obtained from fish and fish oils) is low.
      Further, the effect of supplementation of n-3 PUFAs on metabolic risk factors and
      insulin resistance, except for demonstrated benefit in terms of decreased
      triglycerides, needs further investigation among South Asians. Data also show
      that intake of monounsaturated fatty acids (MUFAs) ranged from 4.7% to 16.4%en in
      developing countries, and supplementing it from olive, canola, mustard,
      groundnut, and rice bran oils may reduce metabolic risk. In addition, in some
      developing countries, intake of n-6 PUFAs (obtained from sunflower, safflower,
      corn, soybean, and sesame oils) and trans-fatty acids (TFAs) is increasing. These
      data show imbalanced consumption of fats and oils in developing countries, which
      may have potentially deleterious metabolic and glycemic consequences, although
      more research is needed. In view of the rapid rise of T2DM in developing
      countries, more aggressive public health awareness programs coupled with
      governmental action and clear country-specific guidelines are required, so as to
      promote widespread use of healthy oils, thus curbing intake of SFAs and TFAs, and
      increasing intake of n-3 PUFAs and MUFAs. Such actions would contribute to
      decelerating further escalation of "epidemics" of obesity, the metabolic
      syndrome, and T2DM in developing countries.

PMID- 20823490
TI  - Moving from efficacy to effectiveness: red palm oil's role in preventing vitamin
      A deficiency.
AB  - Vitamin A deficiency is one of the most widespread nutritional deficiencies
      worldwide. Hundreds of millions of children and tens of millions of women living
      in Sub-Saharan Africa and Southeast Asia are at particularly high risk of the
      adverse health consequences associated with this largely preventable condition.
      Red palm oil comes from oil palms that are traditionally grown in tropical
      regions of West Africa and are now cultivated on a large-scale commercial basis
      in Southeast Asia. Red palm oil is the richest naturally occurring source of beta
      carotene, a carotenoid that the human body can convert into usable vitamin A
      (retinol). This paper reviews a series of key intervention studies designed to
      investigate the impact of using red palm oil-based interventions to improve
      vitamin A status. These included studies from Africa, Asia, and Latin America in
      which red palm oil was used (or proposed for use) (1) as a dietary supplement,
      (2) as an in-home fortificant, (3) to fortify foods used for distribution in
      targeted supplementary feeding programs, and (4) to fortify staple food products.
      Overall, the results suggest that red palm oil is highly efficacious in improving
      vitamin A status among populations at risk of vitamin A deficiency. The time has
      come to move beyond trials of biological efficacy and focus on conducting
      operational research projects, effectiveness trials, and cost-benefit analyses
      that will help expand the use of red palm oil in areas where it is likely to be
      well accepted but remains underutilized as a dietary source of provitamin A.

PMID- 20823492
TI  - The value of tocotrienols in the prevention and treatment of cancer.
AB  - Tocopherols and tocotrienols represent the 2 subgroups that make up the vitamin E
      family of compounds, but only tocotrienols display potent anticancer activity.
      Although in vitro experimental evidence has been very promising, oral
      supplementation of tocotrienols in animal and human studies has produced
      inconsistent results. However, recent studies have now clarified the reasons for
      these discrepancies observed between in vitro and in vivo studies. Oral
      absorption of tocotrienols into the circulation is mediated in large part by
      carrier transporter systems that display saturation and apparently down
      regulation when exposed to high concentrations of tocotrienols. To circumvent
      these limitations in oral absorption of tocotrienols, investigators have
      developed novel prodrug derivatives and nanoparticle delivery systems that
      greatly enhance tocotrienol bioavailability and therapeutic responsiveness.
      Additional studies have also demonstrated that combined treatment of tocotrienols
      with other traditional chemotherapeutic agents results in a synergistic
      anticancer response, and this synergistic response was further enhanced when
      these agents were encapsulated in a nanoparticle delivery system. Taken together,
      these findings clarify the limitations of oral tocotrienol administration and
      provide novel alternative drug-delivery systems that circumvent these limitations
      and greatly enhance the therapeutic effectiveness of tocotrienols in the
      prevention and treatment of cancer.

PMID- 20823491
TI  - Palm oil-derived natural vitamin E alpha-tocotrienol in brain health and disease.
AB  - A growing body of research supports that members of the vitamin E family are not
      redundant with respect to their biological function. Palm oil derived from Elaeis
      guineensis represents the richest source of the lesser characterized vitamin E,
      alpha-tocotrienol. One of 8 naturally occurring and chemically distinct vitamin E
      analogs, alpha-tocotrienol possesses unique biological activity that is
      independent of its potent antioxidant capacity. Current developments in alpha
      tocotrienol research demonstrate neuroprotective properties for the lipid-soluble
      vitamin in brain tissue rich in polyunsaturated fatty acids (PUFAs). Arachidonic
      acid (AA), one of the most abundant PUFAs of the central nervous system, is
      highly susceptible to oxidative metabolism under pathologic conditions. Cleaved
      from the membrane phospholipid bilayer by cytosolic phospholipase A(2), AA is
      metabolized by both enzymatic and nonenzymatic pathways. A number of
      neurodegenerative conditions in the human brain are associated with disturbed
      PUFA metabolism of AA, including acute ischemic stroke. Palm oil-derived alpha
      tocotrienol at nanomolar concentrations has been shown to attenuate both
      enzymatic and nonenzymatic mediators of AA metabolism and neurodegeneration. On a
      concentration basis, this represents the most potent of all biological functions
      exhibited by any natural vitamin E molecule. Despite such therapeutic potential,
      the scientific literature on tocotrienols accounts for roughly 1% of the total
      literature on vitamin E, thus warranting further investment and investigation.

PMID- 20823493
TI  - Role of NF-kappaB in the anti-inflammatory effects of tocotrienols.
AB  - The NF-kappaB family of transcription factors regulates genes that are critical
      for inflammation and immunity. In most cells, NF-kappaB function is induced upon
      activation of cells by various stimuli. However, constitutive NF-kappaB activity
      is an equally important aspect of NF-kappaB function that is particularly
      relevant to chronic inflammation and cancer. Here, we provide a brief overview of
      NF-kappaB biology and discuss the role of NF-kappaB in mediating the anti
      inflammatory effects of tocotrienols The NF-kappaB family of transcription
      factors is a central player in the regulation of inflammation and immune
      responses. Consequently, NF-kappaB dysregulation has been implicated in diverse
      human pathologies ranging from autoimmune diseases to cancers. Additionally,
      there is considerable interest in the contribution of NF-kappaB-mediated chronic
      inflammation in aging. Because NF-kappaB-dependent gene regulation is important
      in virtually all mammalian cell types, it is critical to keep in mind some basic
      features of its functions when considering interventional therapeutics.

PMID- 20823495
TI  - Robust gold nanoparticles stabilized by trithiol for application in
      chemiresistive sensors.
AB  - The use of gold nanoparticles coated with an organic monolayer of thiol for
      application in chemiresistive sensors was initiated in the late 1990s; since
      then, such types of sensors have been widely pursued due to their high
      sensitivities and reversible responses to volatile organic compounds (VOCs).
      However, a major issue for chemical sensors based on thiol-capped gold
      nanoparticles is their poor long-term stability as a result of slow degradation
      of the monothiol-to-gold bonds. We have devised a strategy to overcome this
      limitation by synthesizing a more robust system using Au nanoparticles capped by
      trithiol ligands. Compared to its monothiol counterpart, the new system is
      significantly more stable and also shows improved sensitivity towards different
      types of polar or non-polar VOCs. Thus, the trithiol-Au nanosensor shows great
      promise for use in real world applications.

PMID- 20823496
TI  - A graphene sheet exfoliated with microwave irradiation and interlinked by carbon
      nanotubes for high-performance transparent flexible electrodes.
AB  - High quality graphene was obtained though microwave irradiated expansion
      following a solution process. This method is facile, inexpensive, and produces
      usable results. Ultrathin, uniform graphene films were fabricated at room
      temperature by a vacuum filtration method. Combining carbon nanotubes (CNTs) as
      bridges between graphene flakes allowed the fabrication of high-performance
      conductive films for flexible applications, with conductivities and optical
      properties comparable to commercial ITO: 181 Omega sq(-1) at 82.2% transmittance
      after chemical treatment and doping. With future work, this versatile material
      could well provide an appropriate transparent electrode for flexible optical
      electronics.

PMID- 20823497
TI  - The synthesis and growth mechanism of bamboo-like In2O3 nanowires.
AB  - Bamboo-like In(2)O(3) nanowires are successfully synthesized at 850 degrees C by
      a simple thermal evaporation method with an Au catalyst. The morphology of
      In(2)O(3) nanowires is controlled by the N(2) flow rate. Three different
      morphologies-straight, bamboo-like, and bent and tangled-are obtained under N(2)
      flow rates of 500, 700, and 1000 sccm, respectively. A possible growth mechanism
      of the bamboo-like In(2)O(3) nanowires is proposed. The bamboo-like In(2)O(3)
      nanowires consist of a stem and nodes, which are formed by rapid precipitation
      and oxidation processes of indium from an In-rich Au-In alloy at the bottom of an
      Au catalyst during their growth. Low-temperature photoluminescence of the In(2)O
      nanowires shows a sharp blue emission at 440 nm and a broad orange emission
      centered at 620 nm. The possible origin of the orange emission is discussed.

PMID- 20823498
TI  - Physicochemical characterization and in vivo bioluminescence imaging of
      nanostructured lipid carriers for targeting the brain: apomorphine as a model
      drug.
AB  - Nanostructured lipid carriers (NLCs) were prepared to investigate whether the
      duration of brain targeting and accumulation of drugs in the brain can be
      improved by intravenous delivery. NLCs were developed using cetyl palmitate as
      the lipid matrix, squalene as the cationic surfactant, and Pluronic F68,
      polysorbate 80 and polyethylene glycol as the interfacial additives. Solid lipid
      nanoparticles (SLNs) and lipid emulsions (LEs) were also prepared for comparison.
      An anti-Parkinson's drug, apomorphine, was used as the model drug. Nuclear
      magnetic resonance and differential scanning calorimetry showed possible
      interactions between the solid and liquid lipids in the inner core. The lipid
      nanoparticles with different compositions were characterized by mean size, zeta
      potential, apomorphine encapsulation and in vitro drug release. NLCs were 370-430
      nm in size, which was between the sizes of the SLNs and LEs. A cationic
      surfactant was used to produce a positive surface charge of 42-50 mV. The base
      form of apomorphine was successfully entrapped by NLCs with an entrapment
      percentage of > 60%. The loading of apomorphine in nanoparticles resulted in a
      slower release behavior compared to the aqueous solution, with LEs showing the
      lowest release. In vivo real-time bioluminescence imaging of the rat brain
      revealed that NLCs could be targeted, through certain vessels, to selected brain
      regions. This effect was further confirmed by imaging the entire brain and brain
      slices. The results indicated that NLCs with moderate additives are a promising
      controlled-release and drug-targeting system.

PMID- 20823499
TI  - Direct observation of the semimetal-to-semiconductor transition of individual
      single-crystal bismuth nanowires grown by on-film formation of nanowires.
AB  - We have systematically investigated the semimetal-to-semiconductor transition of
      individual single-crystalline Bi nanowires. For this work, we developed a
      technique to reduce the diameter of Bi nanowires grown by our unique on-film
      formation of nanowires (OFF-ON) method. Cooling down the substrate temperature
      during Bi film deposition by use of liquid nitrogen, film structures with small
      sized grains were obtained. Through thermal annealing of these fine-granular Bi
      films, single-crystalline Bi nanowires can be produced with minimum diameter of
      approximately 20 nm. Elaborative nanofabrication techniques were employed to
      shape state-of-the-art four-probe devices based on the individual small diameter
      Bi nanowires. Diameter-dependent transport measurements on the individual Bi
      nanowires revealed that the semimetal-to-semiconductor transition really occurred
      at about d(w) = 63 nm. Moreover, band structure calculations supported this
      occurrence of the semimetal-to-semiconductor transition.

PMID- 20823500
TI  - Resolution theory, and static and frequency-dependent cross-talk in piezoresponse
      force microscopy.
AB  - Probing the functionality of materials locally by means of scanning probe
      microscopy (SPM) requires a reliable framework for identifying the target signal
      and separating it from the effects of surface morphology and instrument non
      idealities, e.g. instrumental and topographical cross-talk. Here we develop a
      linear resolution theory framework in order to describe the cross-talk effects,
      and apply it for elucidation of frequency-dependent cross-talk mechanisms in
      piezoresponse force microscopy. The use of a band excitation method allows
      electromechanical/electrical and mechanical/topographic signals to be
      unambiguously separated. The applicability of a functional fit approach and
      multivariate statistical analysis methods for identification of data in band
      excitation SPM is explored.

PMID- 20823501
TI  - Understanding atomic-resolved STM images on TiO2(110)-(1 x 1) surface by DFT
      calculations.
AB  - We present a combination of experimental STM images and DFT calculations to
      understand the atomic scale contrast of features found in high-resolution STM
      images. Simulating different plausible structural models for the tip, we have
      been able to reproduce various characteristics previously reported in
      experimental images on TiO(2)(110)-(1 x 1) under controlled UHV conditions. Our
      results allow us to determine the influence of different chemical and
      morphological tip terminations on the atomic-resolution STM images of the
      TiO(2)(110)-(1 x 1) surface. The commonest images have been properly explained
      using standard models for a W tip, either clean or with a single O atom located
      at the apex. Furthermore, a double transfer of oxygen atoms can account for
      different types of bizarre atomic-resolution features occasionally seen, and not
      conclusively interpreted before. Importantly, we discuss how typical point
      defects are imaged on this surface by different tips, namely bridging O vacancies
      and adsorbed OH groups.

PMID- 20823502
TI  - Unique nanopore pattern formation by focused ion beam guided anodization.
AB  - The fabrication of ordered porous templates in large areas with sophisticated
      patterns beyond mono-sized pores in hexagonal packing remains a great technical
      challenge. Conventional anodization cannot overcome this limitation and a new
      approach needs to be sought. This study is focused on designing pore patterns in
      square and hexagonal arrangements via focused ion beam lithography with varying
      interpore distances in order to form organized pore arrays with more
      sophisticated patterns. The results demonstrate that the small pores from the
      anodization can be meshed with the larger pores from the focused ion beam
      lithography and unique, complicated nanopore patterns can be created. Large pore
      patterns that cross the grain boundaries are also made possible with the guidance
      of the pores from focused ion beam lithography. A fundamental pore pattern
      formation mechanism is proposed.

PMID- 20823503
TI  - Hippocampal neurons respond uniquely to topographies of various sizes and shapes.
AB  - A number of studies have investigated the behavior of neurons on microfabricated
      topography for the purpose of developing interfaces for use in neural engineering
      applications. However, there have been few studies simultaneously exploring the
      effects of topographies having various feature sizes and shapes on axon growth
      and polarization in the first 24 h. Accordingly, here we investigated the effects
      of arrays of lines (ridge grooves) and holes of microscale (approximately 2
      microm) and nanoscale (approximately 300 nm) dimensions, patterned in quartz
      (SiO2), on the (1) adhesion, (2) axon establishment (polarization), (3) axon
      length, (4) axon alignment and (5) cell morphology of rat embryonic hippocampal
      neurons, to study the response of the neurons to feature dimension and geometry.
      Neurons were analyzed using optical and scanning electron microscopy. The
      topographies were found to have a negligible effect on cell attachment but to
      cause a marked increase in axon polarization, occurring more frequently on sub
      microscale features than on microscale features. Neurons were observed to form
      longer axons on lines than on holes and smooth surfaces; axons were either
      aligned parallel or perpendicular to the line features. An analysis of cell
      morphology indicated that the surface features impacted the morphologies of the
      soma, axon and growth cone. The results suggest that incorporating microscale and
      sub-microscale topographies on biomaterial surfaces may enhance the biomaterials'
      ability to modulate nerve development and regeneration.

PMID- 20823505
TI  - Study of albumin and fibrinogen membranes formed by interfacial crosslinking
      using microfluidic flow.
AB  - Microfluidics enables scale reduction in sample volume with obvious benefits for
      reagent conservation. In contrast to conventional macro-scale flow, microfluidics
      also offers unprecedented control over flow dynamics. In particular, laminar flow
      is readily achieved, allowing for new analytical and synthetic strategies. Here,
      two parallel flows of buffer and xylene were used to create a stable liquid
      liquid interface within linear micro-channels. These, respectively, carried
      protein (albumin or fibrinogen) and an acyl chloride to effect protein
      crosslinking. This created robust, micro-membranes at the interface that bisected
      the fluid channel. Membrane formation was self-limiting, with fibrinogen
      membranes showing greater solute permeability than albumin, based on dye
      transport (Ponceau S, Meldola Blue). The crosslinker isophthaloyl dichloride led
      to thinner, less permeable membranes than terephthaloyl chloride. Larger surface
      area membranes formed at a static liquid-liquid interface served as a more
      physically accessible model and allowed precise electrochemical determination of
      acetaminophen, catechol and peroxide diffusion coefficients, which confirmed the
      greater fibrinogen permeability. Scanning electron microscopy (SEM) of the
      membranes also indicated a higher population of discrete nanopores at the
      fibrinogen surface. A crosslinking pH had a strong effect on overall
      permeability. Adhesion of B50 neuronal cells was demonstrated, and it is proposed
      that the membranes could facilitate cell growth through bidirectional nutrient
      supply in a micrbioreactor format.

PMID- 20823504
TI  - Fabrication of three-dimensional porous cell-laden hydrogel for tissue
      engineering.
AB  - For tissue engineering applications, scaffolds should be porous to enable rapid
      nutrient and oxygen transfer while providing a three-dimensional (3D)
      microenvironment for the encapsulated cells. This dual characteristic can be
      achieved by fabrication of porous hydrogels that contain encapsulated cells. In
      this work, we developed a simple method that allows cell encapsulation and pore
      generation inside alginate hydrogels simultaneously. Gelatin beads of 150-300
      microm diameter were used as a sacrificial porogen for generating pores within
      cell-laden hydrogels. Gelation of gelatin at low temperature (4 degrees C) was
      used to form beads without chemical crosslinking and their subsequent dissolution
      after cell encapsulation led to generation of pores within cell-laden hydrogels.
      The pore size and porosity of the scaffolds were controlled by the gelatin bead
      size and their volume ratio, respectively. Fabricated hydrogels were
      characterized for their internal microarchitecture, mechanical properties and
      permeability. Hydrogels exhibited a high degree of porosity with increasing
      gelatin bead content in contrast to nonporous alginate hydrogel. Furthermore,
      permeability increased by two to three orders while compressive modulus decreased
      with increasing porosity of the scaffolds. Application of these scaffolds for
      tissue engineering was tested by encapsulation of hepatocarcinoma cell line
      (HepG2). All the scaffolds showed similar cell viability; however, cell
      proliferation was enhanced under porous conditions. Furthermore, porous alginate
      hydrogels resulted in formation of larger spheroids and higher albumin secretion
      compared to nonporous conditions. These data suggest that porous alginate
      hydrogels may have provided a better environment for cell proliferation and
      albumin production. This may be due to the enhanced mass transfer of nutrients,
      oxygen and waste removal, which is potentially beneficial for tissue engineering
      and regenerative medicine applications.

PMID- 20823506
TI  - Fabrication of interconnected microporous biomaterials with high hydroxyapatite
      nanoparticle loading.
AB  - Hydroxyapatite (HA) is known to promote osteogenicity and enhance the mechanical
      properties of biopolymers. However, incorporating a large amount of HA into a
      porous biopolymer still remains a challenge. In the present work, a new method
      was developed to produce interconnected microporous poly(glycolic-co-lactic acid)
      (PLGA) with high HA nanoparticle loading. First, a ternary blend comprising
      PLGA/PS (polystyrene)/HA (40/40/20 wt%) was prepared by melt blending under
      conditions for formation of a co-continuous phase structure. Next, a dynamic
      annealing stage under small-strain oscillation was applied to the blend to
      facilitate nanoparticle redistribution. Finally, the PS phase was sacrificially
      extracted, leaving a porous matrix. The results from different characterizations
      suggested that the applied small-strain oscillation substantially accelerated the
      migration of HA nanoparticles during annealing from the PS phase to the PLGA
      phase; nearly all HA particles were uniformly presented in the PLGA phase after a
      short period of annealing. After dissolution of the PS phase, a PLGA material
      with interconnected microporous structure was successfully produced, with a high
      HA loading above 30 wt%. The mechanisms beneath the experimental observations,
      particularly on the enhanced particle migration process, were discussed, and
      strategies for producing highly particle loaded biopolymers with interconnected
      microporous structures were proposed.

PMID- 20823507
TI  - Additive manufacturing for in situ repair of osteochondral defects.
AB  - Tissue engineering holds great promise for injury repair and replacement of
      defective body parts. While a number of techniques exist for creating living
      biological constructs in vitro, none have been demonstrated for in situ repair.
      Using novel geometric feedback-based approaches and through development of
      appropriate printing-material combinations, we demonstrate the in situ repair of
      both chondral and osteochondral defects that mimic naturally occurring
      pathologies. A calf femur was mounted in a custom jig and held within a
      robocasting-based additive manufacturing (AM) system. Two defects were induced:
      one a cartilage-only representation of a grade IV chondral lesion and the other a
      two-material bone and cartilage fracture of the femoral condyle. Alginate
      hydrogel was used for the repair of cartilage; a novel formulation of
      demineralized bone matrix was used for bone repair. Repair prints for both
      defects had mean surface errors less than 0.1 mm. For the chondral defect, 42.8+/
      2.6% of the surface points had errors that were within a clinically acceptable
      error range; however, with 1 mm path planning shift, an estimated approximately
      75% of surface points could likely fall within the benchmark envelope. For the
      osteochondral defect, 83.6+/-2.7% of surface points had errors that were within
      clinically acceptable limits. In addition to implications for minimally invasive
      AM-based clinical treatments, these proof-of-concept prints are some of the only
      in situ demonstrations to-date, wherein the substrate geometry was unknown a
      priori. The work presented herein demonstrates in situ AM, suggests potential
      biomedical applications and also explores in situ-specific issues, including
      geometric feedback, material selection and novel path planning techniques.

PMID- 20823508
TI  - The structure of a family GH25 lysozyme from Aspergillus fumigatus.
AB  - Lysins are important biomolecules which cleave the bacterial cell-wall polymer
      peptidoglycan. They are finding increasing commercial and medical application. In
      order to gain an insight into the mechanism by which these enzymes operate, the X
      ray structure of a CAZy family GH25 ;lysozyme' from Aspergillus fumigatus was
      determined. This is the first fungal structure from the family and reveals a
      modified alpha/beta-barrel-like fold in which an eight-stranded beta-barrel is
      flanked by three alpha-helices. The active site lies toward the bottom of a
      negatively charged pocket and its layout has much in common with other solved
      members of the GH25 and related GH families. A conserved active-site DXE motif
      may be implicated in catalysis, lending further weight to the argument that this
      glycoside hydrolase family operates via a ;substrate-assisted' catalytic
      mechanism.

PMID- 20823509
TI  - Structure of a 14-3-3sigma-YAP phosphopeptide complex at 1.15 A resolution.
AB  - The 14-3-3 proteins are a class of eukaryotic acidic adapter proteins, with seven
      isoforms in humans. 14-3-3 proteins mediate their biological function by binding
      to target proteins and influencing their activity. They are involved in pivotal
      pathways in the cell such as signal transduction, gene expression, enzyme
      activation, cell division and apoptosis. The Yes-associated protein (YAP) is a WW
      domain protein that exists in two transcript variants of 48 and 54 kDa in humans.
      By transducing signals from the cytoplasm to the nucleus, YAP is important for
      transcriptional regulation. In both variants, interaction with 14-3-3 proteins
      after phosphorylation of Ser127 is important for nucleocytoplasmic trafficking,
      via which the localization of YAP is controlled. In this study, 14-3-3sigma has
      been cloned, purified and crystallized in complex with a phosphopeptide from the
      YAP 14-3-3-binding domain, which led to a crystal that diffracted to 1.15 A
      resolution. The crystals belonged to space group C222(1), with unit-cell
      parameters a=82.3, b=112.1, c=62.9 A.

PMID- 20823511
TI  - Near-atomic resolution analysis of BipD, a component of the type III secretion
      system of Burkholderia pseudomallei.
AB  - Burkholderia pseudomallei, the causative agent of melioidosis, possesses a type
      III protein secretion apparatus that is similar to those found in Salmonella and
      Shigella. A major function of these secretion systems is to inject virulence
      associated proteins into target cells of the host organism. The bipD gene of B.
      pseudomallei encodes a secreted virulence factor that is similar in sequence and
      is most likely to be functionally analogous to IpaD from Shigella and SipD from
      Salmonella. Proteins in this family are thought to act as extracellular
      chaperones at the tip of the secretion needle to help the hydrophobic
      translocator proteins enter the target cell membrane, where they form a pore and
      may also link the translocon pore with the secretion needle. BipD has been
      crystallized in a monoclinic crystal form that diffracted X-rays to 1.5 A
      resolution and the structure was refined to an R factor of 16.1% and an Rfree of
      19.8% at this resolution. The putative dimer interface that was observed in
      previous crystal structures was retained and a larger surface area was buried in
      the new crystal form.

PMID- 20823510
TI  - The structural plasticity of Tom71 for mitochondrial precursor translocations.
AB  - Mitochondrial precursors are transported through the translocase of the outer
      membrane (TOM) complex. Tom70/Tom71 is a major surface receptor of the TOM
      complex for mitochondrial precursors and facilitates Hsp70/Hsp90-escorted
      precursor translocation into the mitochondrion. Previous structural studies of
      Tom71 have revealed that it contains an N-terminal and a C-terminal domain and
      that the two domains may remain in an open conformation when binding to
      Hsp70/Hsp90. In a newly obtained crystal form of a complex of Tom71 and the Hsp70
      C-terminus, the N-terminal domain was found to have rotated about 12 degrees
      towards the C-terminal domain compared with the previous determined crystal
      structure of Tom71 in the open conformation. This newly solved structure is
      defined as the ;intermediate conformation'. The domain rearrangements in Tom71
      significantly change the surface hydrophobicity and the volume of the precursor
      binding pocket. This work suggests that Tom70/Tom71-family members may exhibit
      structural plasticity from the intermediate conformation to the fully open
      conformation when complexed with Hsp70/Hsp90. This structural plasticity enables
      the precursor receptors to accommodate different precursor substrates for
      mitochondrial translocation.

PMID- 20823512
TI  - A new crystal form of Lys48-linked diubiquitin.
AB  - Lys48-linked polyubiquitin chains are recognized by the proteasome as a tag for
      the degradation of the attached substrates. Here, a new crystal form of Lys48
      linked diubiquitin (Ub2) was obtained and the crystal structure was refined to
      1.6 A resolution. The structure reveals an ordered isopeptide bond in a trans
      configuration. All three molecules in the asymmetric unit were in the same closed
      conformation, in which the hydrophobic patches of both the distal and the
      proximal moieties interact with each other. Despite the different crystallization
      conditions and different crystal packing, the new crystal structure of Ub2 is
      similar to the previously published structure of diubiquitin, but differences are
      observed in the conformation of the flexible isopeptide linkage.

PMID- 20823513
TI  - An inhibited conformation for the protein kinase domain of the Saccharomyces
      cerevisiae AMPK homolog Snf1.
AB  - AMP-activated protein kinase (AMPK) is a master metabolic regulator for
      controlling cellular energy homeostasis. Its homolog in yeast, SNF1, is activated
      in response to glucose depletion and other stresses. The catalytic (alpha)
      subunit of AMPK/SNF1 in yeast (Snf1) contains a protein Ser/Thr kinase domain
      (KD), an auto-inhibitory domain (AID) and a region that mediates interactions
      with the two regulatory (beta and gamma) subunits. Here, the crystal structure of
      residues 41-440 of Snf1, which include the KD and AID, is reported at 2.4 A
      resolution. The AID is completely disordered in the crystal. A new inhibited
      conformation of the KD is observed in a DFG-out conformation and with the glycine
      rich loop adopting a structure that blocks ATP binding to the active site.

PMID- 20823514
TI  - Structure of the endonuclease IV homologue from Thermotoga maritima in the
      presence of active-site divalent metal ions.
AB  - The most frequent lesion in DNA is at apurinic/apyrimidinic (AP) sites resulting
      from DNA-base losses. These AP-site lesions can stall DNA replication and lead to
      genome instability if left unrepaired. The AP endonucleases are an important
      class of enzymes that are involved in the repair of AP-site intermediates during
      damage-general DNA base-excision repair pathways. These enzymes hydrolytically
      cleave the 5'-phosphodiester bond at an AP site to generate a free 3'-hydroxyl
      group and a 5'-terminal sugar phosphate using their AP nuclease activity.
      Specifically, Thermotoga maritima endonuclease IV is a member of the second
      conserved AP endonuclease family that includes Escherichia coli endonuclease IV,
      which is the archetype of the AP endonuclease superfamily. In order to more fully
      characterize the AP endonuclease family of enzymes, two X-ray crystal structures
      of the T. maritima endonuclease IV homologue were determined in the presence of
      divalent metal ions bound in the active-site region. These structures of the T.
      maritima endonuclease IV homologue further revealed the use of the TIM-barrel
      fold and the trinuclear metal binding site as important highly conserved
      structural elements that are involved in DNA-binding and AP-site repair processes
      in the AP endonuclease superfamily.

PMID- 20823515
TI  - Metal-ion dependence of the active-site conformation of the translesion DNA
      polymerase Dpo4 from Sulfolobus solfataricus.
AB  - Crystal structures of a binary Mg2+-form Dpo4-DNA complex with 1,N2-etheno-dG in
      the template strand as well as of ternary Mg2+-form Dpo4-DNA-dCTP/dGTP complexes
      with 8-oxoG in the template strand have been determined. Comparison of their
      conformations and active-site geometries with those of the corresponding Ca2+
      form complexes revealed that the DNA and polymerase undergo subtle changes as a
      result of the catalytically more active Mg2+ occupying both the A and B sites.

PMID- 20823516
TI  - Structure of a stacked anthraquinone-DNA complex.
AB  - The crystal structure of the telomeric sequence d(UBrAGG) interacting with an
      anthraquinone derivative has been solved by MAD. In all previously studied
      complexes of intercalating drugs, the drug is usually sandwiched between two DNA
      base pairs. Instead, the present structure looks like a crystal of stacked
      anthraquinone molecules in which isolated base pairs are intercalated. Unusual
      base pairs are present in the structure, such as G.G and A.UBr reverse Watson
      Crick base pairs.

PMID- 20823517
TI  - High-resolution structure of an alpha-spectrin SH3-domain mutant with a
      redesigned hydrophobic core.
AB  - The alpha-spectrin SH3 domain (Spc-SH3) is a small modular domain which has been
      broadly used as a model protein in folding studies and these studies have
      sometimes been supported by structural information obtained from the coordinates
      of Spc-SH3 mutants. The structure of B5/D48G, a multiple mutant designed to
      improve the hydrophobic core and as a consequence the protein stability, has been
      solved at 1 A resolution. The crystals belonged to the orthorhombic space group
      P2(1)2(1)2(1), with unit-cell parameters a=24.79, b=37.23, c=62.95 A. This mutant
      also bears a D48G substitution in the distal loop and this mutation has also been
      reported to increase the stability of the protein by itself. The structure of the
      B5/D48G mutant shows a highly packed hydrophobic core and a more ordered distal
      loop compared with previous Spc-SH3 structures.

PMID- 20823518
TI  - Comparison between the orthorhombic and tetragonal forms of the heptamer sequence
      d[GCG(xT)GCG]/d(CGCACGC).
AB  - Cyclohexene nucleic acid (CeNA) building blocks can be introduced into natural
      DNA sequences without a large conformational influence because of the ability of
      the six-membered sugar ring to mimic both the C2'-endo and C3'-endo conformations
      of the naturally occurring ribofuranose sugar ring. The non-self-complementary
      DNA sequence d[GCG(xT)GCG]/d(CGCACGC) with one incorporated CeNA (xT) moiety
      crystallizes in two forms: orthorhombic and tetragonal. The tetragonal form,
      which diffracts to 3 A resolution, is a kinetically stable polymorph of the
      orthorhombic form [Robeyns et al. (2010), Artificial DNA, 1, 1-7], which
      diffracts to 1.17 A resolution and is the thermodynamically stable form of the
      CeNA-incorporated duplex. Here, the two structures are compared, with special
      emphasis on the differences in crystal packing and the irreversible conversion of
      the kinetic form into the high-resolution diffracting thermodynamic form.

PMID- 20823519
TI  - Crystallization and calcium/sulfur SAD phasing of the human EF-hand protein
      S100A2.
AB  - Human S100A2 is an EF-hand protein and acts as a major tumour suppressor, binding
      and activating p53 in a Ca2+-dependent manner. Ca2+-bound S100A2 was crystallized
      and its structure was determined based on the anomalous scattering provided by
      six S atoms from methionine residues and four calcium ions present in the
      asymmetric unit. Although the diffraction data were recorded at a wavelength of
      0.90 A, which is usually not assumed to be suitable for calcium/sulfur SAD, the
      anomalous signal was satisfactory. A nine-atom substructure was determined at 1.8
      A resolution using SHELXD, and SHELXE was used for density modification and phase
      extension to 1.3 A resolution. The electron-density map obtained was well
      interpretable and could be used for automated model building by ARP/wARP.

PMID- 20823520
TI  - Crystallization and preliminary X-ray studies of a galactose-specific lectin from
      the seeds of bitter gourd (Momordica charantia).
AB  - A galactose-specific lectin from the seeds of bitter gourd (Momordica charantia)
      is a four-chain type II ribosome-inactivating protein (RIP) resulting from
      covalent association through a disulfide bridge between two identical copies of a
      two-chain unit. The available structural information on such four-chain RIPs is
      meagre. The bitter gourd lectin was therefore crystallized for structural
      investigation and the crystals have been characterized. It is anticipated that
      the structure of the orthorhombic crystals will be analysed using molecular
      replacement by taking advantage of its sequence, and presumably structural,
      homology to normal two-chain type II RIPs.

PMID- 20823521
TI  - Purification, crystallization and preliminary crystallographic analysis of the
      catalytic domain of the extracellular cellulase CBHI from Trichoderma harzianum.
AB  - The filamentous fungus Trichoderma harzianum has a considerable cellulolytic
      activity that is mediated by a complex of enzymes which are essential for the
      hydrolysis of microcrystalline cellulose. These enzymes were produced by the
      induction of T. harzianum with microcrystalline cellulose (Avicel) under
      submerged fermentation in a bioreactor. The catalytic core domain (CCD) of
      cellobiohydrolase I (CBHI) was purified from the extracellular extracts and
      submitted to robotic crystallization. Diffraction-quality CBHI CCD crystals were
      grown and an X-ray diffraction data set was collected under cryogenic conditions
      using a synchrotron-radiation source.

PMID- 20823522
TI  - Crystallization and preliminary X-ray analysis of PaaAC, the main component of
      the hydroxylase of the Escherichia coli phenylacetyl-coenzyme A oxygenase
      complex.
AB  - The Escherichia coli paa operon encodes enzymes of the phenylacetic acid
      utilization pathway that metabolizes phenylacetate in the form of a coenzyme A
      (CoA) derivative. The phenylacetyl-coenzyme A oxygenase complex, which has been
      postulated to contain five components designated PaaABCDE, catalyzes ring
      hydroxylation of phenylacetyl-CoA. The PaaAC subcomplex shows low sequence
      similarity to other bacterial multicomponent monooxygenases (BMMs) and forms a
      separate branch on the phylogenetic tree. PaaAC, which catalyzes the
      hydroxylation reaction, was purified and crystallized in the absence of a bound
      ligand as well as in complexes with CoA, 3-hydroxybutyryl-CoA, benzoyl-CoA and
      the true substrate phenylacetyl-CoA. Crystals of the ligand-free enzyme belonged
      to space group P2(1)2(1)2(1) and diffracted to 2.65 A resolution, whereas
      complexes with CoA and its derivatives crystallized in space group P4(1)2(1)2 and
      diffracted to approximately 2.0 A resolution. PaaAC represents the first
      crystallized BMM hydroxylase that utilizes a CoA-linked substrate.

PMID- 20823523
TI  - Crystallization and preliminary X-ray crystallographic analysis of the ArsM
      arsenic(III) S-adenosylmethionine methyltransferase.
AB  - Arsenic is the most ubiquitous environmental toxin and carcinogen and
      consequently ranks first on the Environmental Protection Agency's Superfund
      Priority List of Hazardous Substances. It is introduced primarily from
      geochemical sources and is acted on biologically, creating an arsenic
      biogeocycle. A common biotransformation is methylation to monomethylated,
      dimethylated and trimethylated species. Methylation is catalyzed by the ArsM (or
      AS3MT) arsenic(III) S-adenosylmethionine methyltransferase, an enzyme (EC
      2.1.1.137) that is found in members of every kingdom from bacteria to humans.
      ArsM from the thermophilic alga Cyanidioschyzon sp. 5508 was expressed, purified
      and crystallized. Crystals were obtained by the hanging-drop vapor-diffusion
      method. The crystals belonged to the monoclinic space group C2, with unit-cell
      parameters a=84.85, b=46.89, c=100.35 A, beta=114.25 degrees and one molecule in
      the asymmetric unit. Diffraction data were collected at the Advanced Light Source
      and were processed to a resolution of 1.76 A.

PMID- 20823524
TI  - Cloning, expression, purification, crystallization and preliminary
      crystallographic analysis of 5-aminolaevulinic acid dehydratase from Bacillus
      subtilis.
AB  - 5-aminolaevulinic acid dehydratase (ALAD), a crucial enzyme in the biosynthesis
      of tetrapyrrole, catalyses the condensation of two 5-aminolaevulinic acid (ALA)
      molecules to form porphobilinogen (PBG). The gene encoding ALAD was amplified
      from genomic DNA of Bacillus subtilis and the protein was overexpressed in
      Escherichia coli strain BL21 (DE3). The protein was purified and crystallized
      with an additional MGSSHHHHHHSSGLVPRGSH- tag at the N-terminus of the target
      protein. Diffraction-quality single crystals were obtained by the hanging-drop
      vapour-diffusion method. An X-ray diffraction data set was collected at a
      resolution of 2.7 A.

PMID- 20823525
TI  - Crystallization and preliminary crystallographic characterization of the PAS
      domains of EAG and ELK potassium channels.
AB  - Per-Arnt-Sim (PAS) domains are ubiquitous in nature; they are approximately 130
      amino-acid protein domains that adopt a fairly conserved three-dimensional
      structure despite their low degree of sequence homology. These domains constitute
      the N-terminus or, less frequently, the C-terminus of a number of proteins, where
      they exert regulatory functions. PAS-containing proteins generally display two or
      more copies of this motif. In this work, the crystallization and preliminary
      analysis of the PAS domains of two eukaryotic potassium channels from the ether-a
      go-go (EAG) family are reported.

PMID- 20823526
TI  - Preliminary crystallographic analysis of the Escherichia coli antitoxin MqsA
      (YgiT/b3021) in complex with mqsRA promoter DNA.
AB  - The Escherichia coli proteins MqsR and MqsA comprise a novel toxin-antitoxin (TA)
      system. MqsA, the antitoxin, defines a new family of antitoxins because unlike
      other antitoxins MqsA is structured throughout its entire sequence, binds zinc
      and coordinates DNA via its C-terminal and not its N-terminal domain. In order to
      understand how bacterial antitoxins, and MqsA in particular, regulate
      transcription, the MqsA protein was cocrystallized with a 26-mer duplex DNA
      corresponding to the palindromic region of the mqsRA promoter. The merohedrally
      twinned crystal belonged to space group P4(1), with unit-cell parameters a=60.99,
      b=60.99, c=148.60 A. A complete data set was collected to a resolution of 2.1 A.
      The solvent content of the crystal was consistent with the presence of two MqsA
      molecules bound to the duplex DNA in the asymmetric unit.

PMID- 20823527
TI  - Crystallization and preliminary X-ray analysis of formate oxidase, an enzyme of
      the glucose-methanol-choline oxidoreductase family.
AB  - Formate oxidase (FOD), which catalyzes the oxidation of formate to yield carbon
      dioxide and hydrogen peroxide, belongs to the glucose-methanol-choline
      oxidoreductase (GMCO) family. FOD from Aspergillus oryzae RIB40, which has a
      modified FAD as a cofactor, was crystallized at 293 K by the hanging-drop vapour
      diffusion method. The crystal was orthorhombic and belonged to space group
      C222(1). Diffraction data were collected from a single crystal to 2.4 A
      resolution.

PMID- 20823528
TI  - Cloning, expression, crystallization and preliminary X-ray crystallographic
      analysis of a human condensin SMC2 hinge domain with short coiled coils.
AB  - In higher eukaryotes, the condensin complex, which mainly consists of two
      structural maintenance of chromosomes (SMC) subunits, SMC2 (CAP-E) and SMC4 (CAP
      C), plays a critical role in the formation of higher order chromosome structures
      during mitosis. Biochemical and electron-microscopic studies have revealed that
      the SMC2 and SMC4 subunits dimerize through the interaction of their hinge
      domains, forming a characteristic V-shaped heterodimer. However, the details of
      their function are still not fully understood owing to a lack of structural
      information at the atomic level. In this study, the human SMC2 hinge domain with
      short coiled coils was cloned, expressed, purified and crystallized in the
      orthorhombic space group C222 in native and SeMet-derivatized forms. Because of
      the poor diffraction properties of these crystals, the mutant Leu68-->SeMet was
      designed and crystallized in order to obtain the experimental phases. The SeMet
      derivatized crystals of the mutant belonged to space group P3(2)12, with unit
      cell parameters a=b=128.8, c=91.4 A. The diffraction data obtained from a crystal
      that diffracted to 2.4 A resolution were suitable for SAD phasing.

PMID- 20823529
TI  - Crystallization and preliminary X-ray analysis of the major peanut allergen Ara h
      1 core region.
AB  - Peanuts contain some of the most potent food allergens known to date. Ara h 1 is
      one of the three major peanut allergens. As a first step towards three
      dimensional structure elucidation, recombinant Ara h 1 core region was cloned,
      expressed in Escherichia coli and purified to homogeneity. Crystals were obtained
      using 0.1 M sodium citrate pH 5.6, 0.1 M NaCl, 15% PEG 400 as precipitant. The
      crystals diffracted to 2.25 A resolution using synchrotron radiation and belonged
      to the monoclinic space group C2, with unit-cell parameters a=156.521, b=88.991,
      c=158.971 A, beta=107.144 degrees. Data were collected at the BL-38B1 station of
      SPring-8 (Hyogo, Japan).

PMID- 20823530
TI  - The Corynebacterium glutamicum aconitase repressor: scratching around for
      crystals.
AB  - Imperfections on the surfaces of crystallization containers are known to
      influence crystal formation and are thought to do so by helping to overcome the
      nucleation barrier. The intentional creation of imperfections has been widely
      applied to induce crystallization of small molecules, but has not been reported
      for protein crystallization. Here, the crystallization and preliminary X-ray
      analysis of the TetR-type aconitase repressor are reported. This regulator was
      the first transcription factor to be identified in the regulation of the
      tricarboxylic acid cycle in Corynebacterium glutamicum, an organism that is of
      special industrial interest and is an emerging model organism for
      Corynebacterineae. Successful crystallization involved introducing manual
      scratches on the surface of standard commercial plates, which led to a
      substantial improvement in crystal nucleation and quality.

PMID- 20823531
TI  - Cloning, expression, purification, crystallization and preliminary X-ray
      diffraction studies of the catalytic domain of a hyperthermostable endo-1,4-beta
      D-mannanase from Thermotoga petrophila RKU-1.
AB  - Endo-1,4-beta-D-mannanases play key roles in seed germination and fruit ripening
      and have recently received much attention owing to their potential applications
      in the food, detergent and kraft pulp industries. In order to delineate their
      structural determinants for specificity and stability, X-ray crystallographic
      investigations combined with detailed functional studies are being performed. In
      this work, crystals of the catalytic domain of a hyperthermostable endo-1,4-beta
      D-mannanase from Thermotoga petrophila RKU-1 were obtained from three different
      conditions, resulting in two crystalline forms. Crystals from conditions with
      phosphate or citrate salts as precipitant (CryP) belonged to space group
      P2(1)2(1)2(1), with unit-cell parameters a=58.76, b=87.99, c=97.34 A, while a
      crystal from a condition with ethanol as precipitant (CryE) belonged to space
      group I2(1)2(1)2(1), with unit-cell parameters a=91.03, b=89.97, c=97.89 A. CryP
      and CryE diffracted to resolutions of 1.40 and 1.45 A, respectively.

PMID- 20823532
TI  - Crystallographic study of wild-type carbonic anhydrase alpha CA1 from
      Chlamydomonas reinhardtii.
AB  - Carbonic anhydrases (CAs) are ubiquitously distributed and are grouped into three
      structurally independent classes (alphaCA, betaCA and gammaCA). Most alphaCA
      enzymes are monomeric, but alphaCA1 from Chlamydomonas reinhardtii is a dimer
      that is uniquely stabilized by disulfide bonds. In addition, during maturation an
      internal peptide of 35 residues is removed and three asparagine residues are
      glycosylated. In order to obtain insight into the effects of these structural
      features on CA function, wild-type C. reinhardtii alphaCA1 has been crystallized
      in space group P6(5), with unit-cell parameters a=b=134.3, c=120.2 A. The crystal
      diffracted to 1.88 A resolution and a preliminary solution of its crystal
      structure has been obtained by the MAD method.

PMID- 20823533
TI  - Crystallization and preliminary X-ray analysis of a glucansucrase from the dental
      caries pathogen Streptococcus mutans.
AB  - Glucansucrases encoded by Streptococcus mutans play essential roles in the
      synthesis of sticky dental plaques. Based on amino-acid sequence similarity,
      glucansucrases are classified as members of glycoside hydrolase family 70 (GH
      70). Data on the crystal structure of GH 70 glucansucrases have yet to be
      reported. Here, the GH 70 glucansucrase GTF-SI from S. mutans was overexpressed
      in Escherichia coli strain BL21 (DE3), purified to homogeneity and crystallized
      using the hanging-drop vapour-diffusion method. Orthorhombic GTF-SI crystals
      belonging to space group P2(1)2(1)2 were obtained. A diffraction data set was
      collected to 2.1 A resolution.

PMID- 20823534
TI  - Expression, purification and crystallization of Chaetomium thermophilum Cu,Zn
      superoxide dismutase.
AB  - Cu,Zn superoxide dismutase (Cu,ZnSOD) from the thermophilic fungus Chaetomium
      thermophilum was expressed in Pichia pastoris and purified. Crystals were grown
      in over 120 conditions but only those produced with 1.4 M sodium potassium
      phosphate pH 8.2 as precipitant were suitable for structural studies. Data were
      collected to 1.9 A resolution at 100 K from a single crystal using a synchrotron
      radiation source. The crystals belonged to space group P6(1)/P6(5), with unit
      cell parameters a=90.2, c=314.5 A and eight molecules in the asymmetric unit.
      Elucidation of the crystal structure will provide insights into the active site
      of the enzyme and a better understanding of the structure-activity relationship,
      assembly and thermal stability of Cu,ZnSODs.

PMID- 20823535
TI  - Crystallization and preliminary X-ray studies of the C-terminal domain of
      Mycobacterium tuberculosis LexA.
AB  - The C-terminal domain of Mycobacterium tuberculosis LexA has been crystallized in
      two different forms. The form 1 and form 2 crystals belonged to space groups
      P3(1)21 and P3(1), respectively. Form 1 contains one domain in the asymmetric
      unit, while form 2 contains six crystallographically independent domains. The
      structures have been solved by molecular replacement.

PMID- 20823536
TI  - Preliminary crystallographic study of the Streptococcus agalactiae sortases,
      sortase A and sortase C1.
AB  - Sortases are cysteine transpeptidases that are essential for the assembly and
      anchoring of cell-surface adhesins in Gram-positive bacteria. In Streptococcus
      agalactiae (GBS), the pilin-specific sortase SrtC1 catalyzes the polymerization
      of pilins encoded by pilus island 1 (PI-1) and the housekeeping sortase SrtA is
      necessary for cell-wall anchoring of the resulting pilus polymers. These sortases
      are known to utilize different substrates for pilus polymerization and cell-wall
      anchoring; however, the structural correlates that dictate their substrate
      specificity have not yet been clearly defined. This report presents the
      expression, purification and crystallization of SrtC1 (SAG0647) and SrtA
      (SAG0961) from S. agalactiae strain 2603V/R. The GBS SrtC1 has been crystallized
      in three crystal forms and the GBS SrtA has been crystallized in one crystal
      form.

PMID- 20823537
TI  - Crystallization and preliminary X-ray crystallographic analysis of a bacterial
      tyrosinase from Bacillus megaterium.
AB  - Tyrosinases are type 3 copper enzymes that are involved in the production of
      melanin and have two copper ions in the active site. Here, the crystallization
      and primary analysis of a tyrosinase from Bacillus megaterium is reported. The
      purified protein was crystallized in the absence or presence of zinc ions and the
      crystals diffracted to a resolution of 2.0 A. Crystals obtained in the presence
      of zinc belonged to space group P2(1)2(1)2(1), while crystals grown in the
      absence of zinc belonged to space group P2(1). In both space groups the
      asymmetric unit contained a dimer, with minor differences in the crystal density
      and in packing interactions.

PMID- 20823538
TI  - Crystallization and preliminary X-ray analysis of mycophenolic acid-resistant and
      mycophenolic acid-sensitive forms of IMP dehydrogenase from the human fungal
      pathogen Cryptococcus.
AB  - Fungal human pathogens such as Cryptococcus neoformans are becoming an
      increasingly prevalent cause of human morbidity and mortality owing to the
      increasing numbers of susceptible individuals. The few antimycotics available to
      combat these pathogens usually target fungal-specific cell-wall or membrane
      related components; however, the number of these targets is limited. In the
      search for new targets and lead compounds, C. neoformans has been found to be
      susceptible to mycophenolic acid through its target inosine monophosphate
      dehydrogenase (IMPDH); in contrast, a rare subtype of the related C. gattii is
      naturally resistant. Here, the expression, purification, crystallization and
      preliminary crystallographic analysis of IMPDH complexed with IMP and NAD+ is
      reported for both of these Cryptococcus species. The crystals of IMPDH from both
      sources had the symmetry of the tetragonal space group I422 and diffracted to a
      resolution of 2.5 A for C. neoformans and 2.6 A for C. gattii.

PMID- 20823539
TI  - Cloning, purification, crystallization and preliminary X-ray diffraction of the
      OleC protein from Stenotrophomonas maltophilia involved in head-to-head
      hydrocarbon biosynthesis.
AB  - OleC, a biosynthetic enzyme involved in microbial hydrocarbon biosynthesis, has
      been crystallized. Synchrotron X-ray diffraction data have been collected to 3.4
      A resolution. The crystals belonged to space group P3(1)21 or P3(2)21, with unit
      cell parameters a=b=98.8, c=141.0 A.

PMID- 20823540
TI  - Preliminary crystallographic analysis of the N-terminal domain of FILIA, a
      protein essential for embryogenesis.
AB  - FILIA is a component of the subcortical maternal complex that is essential for
      early stage embryogenesis. Its 6xHis-tagged N-terminal domain was expressed in
      Escherichia coli and purified to homogeneity. Two types of crystals formed under
      different crystallization conditions during screening. Orthorhombic crystals
      appeared in a solution containing 1.4 M ammonium sulfate, 0.1 M Tris pH 8.2 and
      12% glycerol, while tetragonal crystals were obtained using 15% PEG 4000 mixed
      with 0.1 M HEPES pH 7.5 and 15% 2-propanol. High-quality diffraction data were
      collected from the two crystal forms to resolutions of 1.8 and 2.2 A,
      respectively, using synchrotron radiation. The Matthews coefficients indicated
      that the P2(1)2(1)2(1) and P4(1)2(1)2 crystals contained two molecules and one
      molecule per asymmetric unit, respectively. A selenomethionine-substituted sample
      failed to crystallize under the native conditions, but another orthorhombic
      crystal form was obtained under different conditions and anomalous diffraction
      data were collected.

PMID- 20823541
TI  - Crystallization and preliminary X-ray crystallographic study of GenX, a lysyl
      tRNA synthetase paralogue from Escherichia coli, in complex with translation
      elongation factor P.
AB  - GenX, a lysyl-tRNA synthetase paralogue from Escherichia coli, was overexpressed
      in E. coli, purified by three chromatographic steps and cocrystallized with a
      lysyl adenylate analogue (LysAMS) by the hanging-drop vapour-diffusion method
      using PEG 4000 as a precipitant. The GenX-LysAMS crystals belonged to the
      triclinic space group P1, with unit-cell parameters a=54.80, b=69.15, c=94.08 A,
      alpha=95.47, beta=106.51, gamma=90.46 degrees, and diffracted to 1.9 A
      resolution. Furthermore, GenX was cocrystallized with translation elongation
      factor P (EF-P), which is believed to be a putative substrate of GenX, and LysAMS
      using PEG 4000 and ammonium sulfate as precipitants. The GenX-EF-P-LysAMS
      crystals belonged to the monoclinic space group P2(1), with unit-cell parameters
      a=105.93, b=102.96, c=119.94 A, beta=99.4 degrees, and diffracted to 2.5 A
      resolution. Structure determination of the E. coli GenX-LysAMS and GenX-EF-P
      LysAMS complexes by molecular replacement was successful and structure
      refinements are now in progress.

PMID- 20823542
TI  - Crystallization and preliminary crystallographic characterization of the iron
      regulated outer membrane lipoprotein FrpD from Neisseria meningitidis.
AB  - Fe-regulated protein D (FrpD) is a Neisseria meningitidis outer membrane
      lipoprotein that may be involved in the anchoring of the secreted repeat in
      toxins (RTX) protein FrpC to the outer bacterial membrane. However, the function
      and biological roles of the FrpD and FrpC proteins remain unknown. Native and
      selenomethionine-substituted variants of recombinant FrpD43-271 protein were
      crystallized using the sitting-drop vapour-diffusion method. Diffraction data
      were collected to a resolution of 2.25 A for native FrpD43-271 protein and to a
      resolution of 2.00 A for selenomethionine-substituted FrpD43-271 (SeMet FrpD43
      271) protein. The crystals of native FrpD43-271 protein belonged to the hexagonal
      space group P6(2) or P6(4), while the crystals of SeMet FrpD43-271 protein
      belonged to the primitive orthorhombic space group P2(1)2(1)2(1).

PMID- 20823543
TI  - Expression, purification and crystallization of Swi5 and the Swi5-Sfr1 complex
      from fission yeast.
AB  - The assembly of the presynaptic filament of recombinases represents the most
      important step in homologous recombination. The formation of the filament
      requires assistance from mediator proteins. Swi5 and Sfr1 have been identified as
      mediators in fission yeast and these proteins form a complex that stimulates
      strand exchange. Here, the expression, purification and crystallization of Swi5
      and its complex with an N-terminally truncated form of Sfr1 (DeltaN180Sfr1) are
      presented. Analytical ultracentrifugation of the purified samples showed that
      Swi5 and the protein complex exist as tetramers and heterodimers in solution,
      respectively. Swi5 was crystallized in two forms belonging to space groups C2 and
      R3 and the crystals diffracted to 2.7 A resolution. Swi5-DeltaN180Sfr1 was
      crystallized in space group P2(1)2(1)2 and the crystals diffracted to 2.3 A
      resolution. The crystals of Swi5 and Swi5-DeltaN180Sfr1 are likely to contain one
      tetramer and two heterodimers in the asymmetric unit, respectively.

PMID- 20823544
TI  - Crystallization and preliminary X-ray diffraction analysis of rat autotaxin.
AB  - Rat autotaxin has been cloned, expressed, purified to homogeneity and
      crystallized via hanging-drop vapour diffusion using PEG 3350 as precipitant and
      ammonium iodide and sodium thiocyanate as salts. The crystals diffracted to a
      maximum resolution of 2.05 A and belonged to space group P1, with unit-cell
      parameters a=53.8, b=63.3, c=70.5 A, alpha=98.8, beta=106.2, gamma=99.8 degrees.
      Preliminary X-ray diffraction analysis indicated the presence of one molecule per
      asymmetric unit, with a solvent content of 47%.

PMID- 20823545
TI  - Mammalian cell expression, purification, crystallization and microcrystal data
      collection of autotaxin/ENPP2, a secreted mammalian glycoprotein.
AB  - Autotaxin (ATX or ENPP2) is a secreted glycosylated mammalian enzyme that
      exhibits lysophospholipase D activity, hydrolyzing lysophosphatidylcholine to the
      signalling lipid lysophosphatidic acid. ATX is an approximately 100 kDa multi
      domain protein encompassing two N-terminal somatomedin B-like domains, a central
      catalytic phosphodiesterase domain and a C-terminal nuclease-like domain.
      Protocols for the efficient expression of ATX from stably transfected mammalian
      HEK293 cells in amounts sufficient for crystallographic studies are reported.
      Purification resulted in protein that crystallized readily, but various attempts
      to grow crystals suitable in size for routine crystallographic structure
      determination were not successful. However, the available micrometre-thick plates
      diffracted X-rays beyond 2.0 A resolution and allowed the collection of complete
      diffraction data to about 2.6 A resolution. The problems encountered and the
      current advantages and limitations of diffraction data collection from thin
      crystal plates are discussed.

PMID- 20823546
TI  - The structure of the genomic Bacillus subtilis dUTPase: novel features in the Phe
      lid.
AB  - dUTPases are a ubiquitous family of enzymes that are essential for all organisms
      and catalyse the breakdown of 2-deoxyuridine triphosphate (dUTP). In Bacillus
      subtilis there are two homotrimeric dUTPases: a genomic and a prophage form.
      Here, the structures of the genomic dUTPase and of its complex with the substrate
      analogue dUpNHpp and calcium are described, both at 1.85 A resolution. The
      overall fold resembles that of previously solved trimeric dUTPases. The C
      terminus, which contains one of the conserved sequence motifs, is disordered in
      both structures. The crystal of the complex contains six independent protomers
      which accommodate six dUpNHpp molecules, with three triphosphates in the trans
      conformation and the other three in the active gauche conformation. The structure
      of the complex confirms the role of several key residues that are involved in
      ligand binding and the position of the catalytic water. Asp82, which has
      previously been proposed to act as a general base, points away from the active
      site. In the complex Ser64 reorients in order to hydrogen bond the phosphate
      chain of the substrate. A novel feature has been identified: the position in the
      sequence of the ;Phe-lid', which packs against the uracil moiety, is adjacent to
      motif III, whereas in all other dUTPase structures the lid is in a conserved
      position in motif V of the flexible C-terminal arm. This requires a
      reconsideration of some aspects of the accepted mechanism.

PMID- 20823547
TI  - Atomic resolution studies of haloalkane dehalogenases DhaA04, DhaA14 and DhaA15
      with engineered access tunnels.
AB  - The haloalkane dehalogenase DhaA from Rhodococcus rhodochrous NCIMB 13064 is a
      bacterial enzyme that shows catalytic activity for the hydrolytic degradation of
      the highly toxic industrial pollutant 1,2,3-trichloropropane (TCP). Mutagenesis
      focused on the access tunnels of DhaA produced protein variants with
      significantly improved activity towards TCP. Three mutants of DhaA named DhaA04
      (C176Y), DhaA14 (I135F) and DhaA15 (C176Y + I135F) were constructed in order to
      study the functional relevance of the tunnels connecting the buried active site
      of the protein with the surrounding solvent. All three protein variants were
      crystallized using the sitting-drop vapour-diffusion technique. The crystals of
      DhaA04 belonged to the orthorhombic space group P2(1)2(1)2(1), while the crystals
      of DhaA14 and DhaA15 had triclinic symmetry in space group P1. The crystal
      structures of DhaA04, DhaA14 and DhaA15 with ligands present in the active site
      were solved and refined using diffraction data to 1.23, 0.95 and 1.22 A,
      resolution, respectively. Structural comparisons of the wild type and the three
      mutants suggest that the tunnels play a key role in the processes of ligand
      exchange between the buried active site and the surrounding solvent.

PMID- 20823548
TI  - Percentile-based spread: a more accurate way to compare crystallographic models.
AB  - The comparison of biomacromolecular crystal structures is traditionally based on
      the root-mean-square distance between corresponding atoms. This measure is
      sensitive to the presence of outliers, which inflate it disproportionately to
      their fraction. An alternative measure, the percentile-based spread (p.b.s.), is
      proposed and is shown to represent the average variation in atomic positions more
      adequately. It is discussed in the context of isomorphous crystal structures,
      conformational changes and model ensembles generated by repetitive automated
      rebuilding.

PMID- 20823549
TI  - Structures of the nucleotide-binding domain of the human ABCB6 transporter and
      its complexes with nucleotides.
AB  - The human ATP-binding cassette (ABC) transporter ABCB6 is involved in haem
      precursor transport across the mitochondrial membrane. The crystal structure of
      its nucleotide-binding domain (NBD) has been determined in the apo form and in
      complexes with ADP, with ADP and Mg(2+) and with ATP at high resolution. The
      overall structure is L-shaped and consists of two lobes, consistent with other
      reported NBD structures. Nucleotide binding is mediated by the highly conserved
      Tyr599 and the Walker A motif, and induces notable structural changes. Structural
      comparison with other structurally characterized NBDs and full-length ABC
      transporters gives the first insight into the possible catalytic mechanism of
      ABCB6 and the role of the N-terminal helix alpha(1) in full-length ABCB6.

PMID- 20823550
TI  - Inclusion of weak high-resolution X-ray data for improvement of a group II intron
      structure.
AB  - It is common to report the resolution of a macromolecular structure with the
      highest resolution shell having an averaged I/sigma(I) > or = 2. Data beyond the
      resolution thus defined are weak and often poorly measured. The exclusion of
      these weak data may improve the apparent statistics and also leads to claims of
      lower resolutions that give some leniency in the acceptable quality of refined
      models. However, the inclusion of these data can provide additional strong
      constraints on atomic models during structure refinement and thus help to correct
      errors in the original models, as has recently been demonstrated for a protein
      structure. Here, an improved group II intron structure is reported arising from
      the inclusion of these data, which helped to define more accurate solvent models
      for density modification during experimental phasing steps. With the improved
      resolution and accuracy of the experimental phases, extensive revisions were made
      to the original models such that the correct tertiary interactions of the group
      II intron that are essential for understanding the chemistry of this ribozyme
      could be described.

PMID- 20823551
TI  - Structural study and thermodynamic characterization of inhibitor binding to
      lumazine synthase from Bacillus anthracis.
AB  - The crystal structure of lumazine synthase from Bacillus anthracis was solved by
      molecular replacement and refined to R(cryst) = 23.7% (R(free) = 28.4%) at a
      resolution of 3.5 A. The structure reveals the icosahedral symmetry of the enzyme
      and specific features of the active site that are unique in comparison with
      previously determined orthologues. The application of isothermal titration
      calorimetry in combination with enzyme kinetics showed that three designed
      pyrimidine derivatives bind to lumazine synthase with micromolar dissociation
      constants and competitively inhibit the catalytic reaction. Structure-based
      modelling suggested the binding modes of the inhibitors in the active site and
      allowed an estimation of the possible contacts formed upon binding. The results
      provide a structural framework for the design of antibiotics active against B.
      anthracis.

PMID- 20823552
TI  - Performance of phased rotation, conformation and translation function: accurate
      protein model building with tripeptidic and tetrapeptidic fragments.
AB  - The automatic building of protein structures with tripeptidic and tetrapeptidic
      fragments was investigated. The oligopeptidic conformers were positioned in the
      electron-density map by a phased rotation, conformation and translation function
      and refined by a real-space refinement. The number of successfully located
      fragments lay within the interval 75-95% depending on the resolution and phase
      quality. The overlaps of partially located fragments were analyzed. The correctly
      positioned fragments were connected into chains. Chains formed in this way were
      extended directly into the electron density and a sequence was assigned. In the
      initial stage of the model building the number of located fragments was between
      60% and 95%, but this number could be increased by several cycles of reciprocal
      space refinement and automatic model rebuilding. A nearly complete structure can
      be obtained on the condition that the resolution is reasonable. Computer graphics
      will only be needed for a final check and small corrections.

PMID- 20823553
TI  - A smooth and differentiable bulk-solvent model for macromolecular diffraction.
AB  - Inclusion of low-resolution data in macromolecular crystallography requires a
      model for the bulk solvent. Previous methods have used a binary mask to
      accomplish this, which has proven to be very effective, but the mask is
      discontinuous at the solute-solvent boundary (i.e. the mask value jumps from zero
      to one) and is not differentiable with respect to atomic parameters. Here, two
      algorithms are introduced for computing bulk-solvent models using either a
      polynomial switch or a smoothly thresholded product of Gaussians, and both models
      are shown to be efficient and differentiable with respect to atomic coordinates.
      These alternative bulk-solvent models offer algorithmic improvements, while
      showing similar agreement of the model with the observed amplitudes relative to
      the binary model as monitored using R, R(free) and differences between
      experimental and model phases. As with the standard solvent models, the
      alternative models improve the agreement primarily with lower resolution (>6 A)
      data versus no bulk solvent. The models are easily implemented into
      crystallographic software packages and can be used as a general method for bulk
      solvent correction in macromolecular crystallography.

PMID- 20823554
TI  - High-speed crystal detection and characterization using a fast-readout detector.
AB  - A novel raster-scanning method combining continuous sample translation with the
      fast readout of a Pilatus P6M detector has been developed on microfocus beamline
      I24 at Diamond Light Source. This fast grid-scan tool allows the rapid evaluation
      of large sample volumes without the need to increase the beam size at the sample
      through changes in beamline hardware. A slow version is available for slow
      readout detectors. Examples of grid-scan use in centring optically invisible
      samples and in detecting and characterizing numerous microcrystals on a mesh-like
      holder illustrate the most common applications of the grid scan now in routine
      use on I24.

PMID- 20823555
TI  - Molecular recognition between Escherichia coli enolase and ribonuclease E.
AB  - In Escherichia coli and many other bacterial species, the glycolytic enzyme
      enolase is a component of the multi-enzyme RNA degradosome, an assembly that is
      involved in RNA processing and degradation. Enolase is recruited into the
      degradosome through interactions with a small recognition motif located within
      the degradosome-scaffolding domain of RNase E. Here, the crystal structure of
      enolase bound to its cognate site from RNase E (residues 823-850) at 1.9 A
      resolution is presented. The structure suggests that enolase may help to organize
      an adjacent conserved RNA-binding motif in RNase E.

PMID- 20823556
TI  - Is too 'creative' language acceptable in crystallography?
AB  - While figures of speech are often useful and even educational, flashy titles
      combined with hyperbolae and imprecise language can mislead or deceive non
      specialist readers and should therefore be avoided. The possibility of such
      confusion exists when poorly defined terms like ;structure quality' or ;super
      resolution' are used to describe a protein structure.

PMID- 20823557
TI  - Medicinal herb research: serum pharmacological method and plasma pharmacological
      method.
AB  - Serum pharmacological method has generally been used in herb studies. However,
      preparation of test serum for ex vivo experiment is an intricate process: besides
      pretreatment (heat or chemicals), it involves the proteolytic cascades of
      coagulation along with fibrinolysis, complement and kinin systems, as well as
      platelet and leukocyte activation resulting in release reactions. These processes
      deviate serum sample components away from the original in vivo state, and
      possibly also have effects on the absorbed herbal components and their downstream
      effectors in blood. The conclusions drawn from serum pharmacological method are
      at least partially uncertain in its validity. These processes can be avoided by
      anticoagulation. Compared to those of the serum, constituents of plasma are
      better reflectors of the in vivo physiological/pathological state and medicinal
      herb-induced changes. Therefore, we have advocated the adoption of plasma
      pharmacological method in ex vivo experiments of herb studies. Recent studies
      including our work demonstrated that the constituents and biological activities
      are partially different between absorbed medicinal herbs in plasma and serum.
      This review summarizes the experimental evidence supporting the feasibility of
      plasma pharmacological method and discusses the reasons and facts that flaw the
      serum pharmacological method. But serum pharmacological method can be used if
      anticoagulants interfere with experiments. It should be emphasized that the
      domination between plasma and serum pharmacological methods is different
      depending on the usage. Indeed, the pros and cons of both methods as well as the
      appropriate choices of coagulants in different ex vivo experimental settings
      remain to be further elucidated.

PMID- 20823558
TI  - Development of an in vitro drug release assay of PEGylated liposome using bovine
      serum albumin and high temperature.
AB  - In this study, to establish the conditions of a drug release assay for PEGylated
      liposome formulations that relates with the drug stability profile in serum in
      vivo, the influences of incubation temperature and serum protein in the release
      buffer were examined using liposomal doxorubicin (DXR). In in vitro drug release
      assays, a PEGylated liposomal DXR in phosphate buffered saline (PBS) at 37
      degrees C showed higher drug release rate than non-PEGylated formulation although
      PEGylated liposomal DXR had higher stability than an equivalent non-PEGylated
      formulation following intravenous injection. When bovine serum albumin (BSA) and
      increased temperature, 50 degrees C, were used to accelerate drug release from
      the liposomes and to mimic in vivo result, non-PEGylated liposomal DXR showed
      conversely higher release than a PEGylated formulation. Since high temperature
      increased BSA adsorption onto liposomes, BSA may cause non-PEGylated liposomes
      instability more than PEGylated ones, resulting in the reverse of the drug
      release rate of both liposomes. This finding suggested that the conditions in the
      drug release assay with PEGylated liposomal DXR may be able to be set by a
      combination of BSA and providing additional thermal energy.

PMID- 20823559
TI  - Effect of delta-tocotrienol on melanin content and enzymes for melanin synthesis
      in mouse melanoma cells.
AB  - In the present study, we investigated the dose-dependent effect of delta
      tocotrienol long term (48, 72 h) on the melanin content of cells treated with
      delta-tocotrienol, and whether cells treated with delta-tocotrienol for long a
      time show cytotoxicity. We also examined whether other enzymes responsible for
      melanin biosynthesis, tyrosinase-related protein-1 (TRP-1) and -2 (TRP-2), are
      involved in the decrease in melanin levels. Protein levels in cells treated with
      25 or 50 microM delta-tocotrienol for 48 h or 72 h were similar to those in
      control cells. Melanin content decreased by 44 (25 microM delta-tocotrienol) to
      50% (50 microM) at 48 h, and by 14 to 21% at 72 h, compared to control levels.
      Tyrosinase activity, amounts of tyrosinase and TRP-1 decreased dependent on dose
      : by 50 (25 microM delta-tocotrienol) to 75% (50 microM), 20 to 45% and 42 to 82%
      at 48 h, and by 25 to 50%, 75 to 80% and 78 to 77% at 72 h, respectively.
      Although the amount of TRP-2 increased by 20% on treatment with 25 microM delta
      tocotrienol for 48 h, it decreased by 52% on treatment with 50 microM delta
      tocotrienol for 48 h. The amount of TRP-2 dose-dependently decreased by 55% and
      75% on 72 h by treatment with 25 and 50 microM delta-tocotrienol, respectively.
      From these findings, delta-tocotrienol at up to 50 microM dose-dependently caused
      a reduction in melanin content by the decrease of TRP-1 and TRP-2 as well as
      tyrosinase, and no cytotoxicity.

PMID- 20823560
TI  - Protective effect of combination of sulforaphane and riluzole on glutamate
      mediated excitotoxicity.
AB  - Threohydroxyaspartate (THA) causes glutamate excitotoxicity in motor neurons in
      organotypic culture of rat spinal cord. Some drugs, including sulforaphane (SF)
      and riluzole, can protect motor neuron against excitotoxicity. It has been
      demonstrated that SF is a potent inducer of Phase II enzymes, while riluzole is a
      classic anti-glutamate agent. The objective of the current study is to
      investigate whether the combination of SF and riluzole is superior to either one
      used alone. In our study, the combination of SF with riluzole not only stimulates
      the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), reduced
      nicotinamide adenine dinucleotide phosphate (NADPH): quinone oxidoreductase 1
      (NQO1) and heme oxygenase 1 (HO-1), but also reduces the extracellular
      accumulation of glutamate. When used at optimal doses, SF (10 microM) and
      riluzole (5 microM), either alone or in combination, all exert significant and
      similar neuroprotection, as measured by the number of motor neuron, medium
      malondialdehyde (MDA) level and lactate dehydrogenase (LDH) level. When used at
      low doses, the combination is better than each agent used alone. In conclusion,
      these results suggest the potential utility of combination use of SF and riluzole
      for protection of motor neuron against excitotoxicity.

PMID- 20823561
TI  - Caffeic acid phenethyl ester inhibits differentiation to adipocytes in 3T3-L1
      mouse fibroblasts.
AB  - We investigated the inhibitory effect of caffeic acid phenethyl ester (CAPE) on
      the differentiation of 3T3-L1 mouse fibroblasts to adipocytes. 3T3-L1 cells were
      differentiated for adipocytes given high glucose Dulbecco's modified Eagle's
      medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 1 microM
      dexamethasone (DEX), 500 microM isobutylmethylxanthine (IBMX), and 5 microg/ml
      insulin for 7 days. After differentiation, cells were stained with Oil-Red-O to
      detect oil droplets in adipocytes. Additionally, the cells were lysed and
      measured for triglyceride contents. Total RNA was isolated from differentiated
      cells on day 0, 4 and 7. Then, RNA was analyzed using reverse transcription (RT)
      polymerase chain reaction (PCR). CAPE dose-dependently suppressed oil droplet
      accumulation and reduced the droplet size. These findings showed that CAPE at
      concentrations of 25 to 50 microM could significantly inhibit triglyceride
      deposition (p<0.05). Treatment of 3T3-L1 with CAPE reduced the mRNA levels of
      peroxisome proliferator-activated receptor (PPAR) gamma and CCAAT/enhancer
      binding protein (C/EBPalpha). Fatty acid synthase (Fas) and adipocyte-specific
      fatty acid binding protein (aP2) are known to be associated with lipid metabolism
      in adipocytes, and both Fas mRNA and aP2 mRNA were significantly suppressed by
      CAPE treatment. These findings suggested that CAPE suppresses 3T3-L1
      differentiation to adipocytes through inhibition of PPARgamma, C/EBPalpha, Fas
      and aP2 expression.

PMID- 20823562
TI  - In vitro antibacterial activity of panduratin A against enterococci clinical
      isolates.
AB  - Panduratin A, a natural chalcone compound isolated from the rhizome of fingerroot
      (Boesenbergia rotunda (L.) MANSF. A). The antibacterial activity of panduratin A
      against clinical enterococci isolates was compared in terms of minimum inhibitory
      concentration (MIC) and minimal bactericidal concentration (MBC) to those of
      commonly used antimicrobials, according to the CLSI guidelines. Time-kill curves
      were constructed to assess the concentration between MIC and bactericidal
      activity of panduratin A at concentrations ranging from 0x MIC to 4x MIC. The
      activity of panduratin A against biofilm-producing enterococcal strains was also
      evaluated. The growth of all clinical enterococci isolates (n=23) were inhibited
      by panduratin A at a concentration of 2 microg/ml. Panduratin A was able to kill
      all clinical enterococci isolates with a MBC of 8 microg/ml. The time-kill curves
      demonstrated that the bactericidal endpoint for clinical enterococci was reached
      after 30 min of incubation at a panduratin A concentration of 4x MIC. The growth
      of biofilm-producing enterococcal strains can be inhibited and eradicated by
      panduratin A at concentrations of <or=4 microg/ml and <or=16 microg/ml,
      respectively. The antibacterial activity of panduratin A against all clinical
      enterococci isolates was generally more potent than commonly used antimicrobials.
      Panduratin A has stronger activity against biofilm-producing enterococcal strains
      than daptomycin and linezolid. Panduratin A is an antimicrobial agent with high
      in vitro activity against clinical enterococci, including organisms resistant to
      other antimicrobials.

PMID- 20823563
TI  - 7-O-methylaromadendrin stimulates glucose uptake and improves insulin resistance
      in vitro.
AB  - The stimulation of glucose uptake into peripheral tissues is an important
      mechanism for the removal of glucose in blood and for the management of diabetes
      mellitus (DM). Since recent results have demonstrated the beneficial effects of
      flavonoids in relation to DM, this study was designed to examine the effects of 7
      O-methylaromadendrin (7-O-MA), a flavonoid isolated from Inula viscosa, on
      glucose uptake into liver and fat tissue, and investigate the molecular
      mechanisms involved. 7-O-MA at 10 microM significantly stimulated insulin-induced
      glucose uptake measured by 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy
      D-glucose (2-NBDG) in both human hepatocellular liver carcinoma (HepG2) cells and
      differentiated 3T3-L1 adipocytes. Adipocyte-specific fatty acid binding protein
      (aP2) gene expression was increased by 7-O-MA in adipocytes, and both gene and
      protein level of peroxisome proliferator-activated receptor gamma2 (PPARgamma2)
      was also increased. Moreover, 7-O-MA stimulated the reactivation of insulin
      mediated phosphorylation of phosphatidylinositol 3-kinase (PI3K)-linked protein
      kinase B (Akt/PKB) and adenosine 5'-monophosphate-activated protein kinase (AMPK)
      in high glucose-induced, insulin-resistant HepG2 cells, and this effect was
      blocked by either LY294002, a PI3K inhibitor, or compound C, an AMPK inhibitor.
      Therefore, these results suggest that 7-O-MA might stimulate glucose uptake via
      PPARgamma2 activation and improve insulin resistance via PI3K and AMPK-dependent
      pathways, and be a potential candidate for the management of type 2 DM.

PMID- 20823564
TI  - A novel sphingosine-1-phosphate receptor 1 antagonist prevents the proliferation
      and relaxation of vascular endothelial cells by sphingosine-1-phosphate.
AB  - A sphingosine-1-phosphate receptor 1 (S1P1) antagonist is expected to be an anti
      angiogenic compound; however, there are few reports that demonstrated that a S1P1
      inhibitor improved the disease state in an angiogenic animal model. Since we
      determined that a prototype S1P1 antagonist was an in vivo angiogenesis
      inhibitor, we developed the derivatives to acquire more effective compounds. In
      this report, we show the S1P1 antagonistic activity of some representatives,
      especially compound 5 {sodium 4-[(4-butoxyphenyl)thio]-2'-[{4
      [(heptylthio)methyl]-2-hydroxyphenyl}(hydroxy)methyl]biphenyl-3-sulfonate}. The
      IC50 values calculated from an intracellular cyclic AMP measurement assay and a
      [33P]sphingosine-1-phosphate (Sph-1-P)/S1P1 binding assay were 38 and 200 nM,
      respectively. A subtype specificity test for the other Sph-1-P receptors showed
      that compound 5 was the S1P1-directional antagonist. It also inhibited the
      proliferation, migration, and tube formation of human umbilical vein endothelial
      cells stimulated by Sph-1-P with the IC50 values of 18, 650, and 230 nM,
      respectively. A cytotoxicity assay concurrently performed with a tube formation
      assay supported the hypothesis that these biological effects were not due to its
      cytotoxicity. Furthermore, administration (10 mg/kg, intravenously) to
      anesthetized Sprague-Dawley rats inhibited Sph-1-P-induced hypotension by 100-90%
      for 30 min. This is presumably through the inhibition of Sph-1-P-induced
      vasorelaxation, mainly by the blocking of S1P1 and/or S1P3. Taken together, these
      results show that compound 5 is an inhibitor of in vitro and in vivo Sph-1-P
      signaling, and that it will be useful to elucidate the in vivo effect of Sph-1-P
      on vascular endothelial cells.

PMID- 20823565
TI  - Effects of metformin on rosiglitazone-induced cardiac hypertrophy in mice.
AB  - Thiazolidinediones (TZD) can cause adipose tissue accumulation and myocardial
      hypertrophy. This study aimed to determine if combined Metformin (Glucophage) and
      Rosiglitazone (Avandia) could reduce the risk of heart failure caused by
      Rosiglitazone in BALB/c mice. BALB/c mice were treated with oral
      Rosiglitazone/Metformin twice daily for four weeks. Metformin or Rosiglitazone
      alone and non-treated mice acted as double control. Myocardial hypertrophy and
      associated side effects of the combined therapy were determined through isolated
      heart and body weights. Reverse transcription-polymerase chain reaction (RT-PCR)
      and Western blot were applied to evaluate expression of sulfonylurea receptor 2A
      (SUR2A) and Kir 6.2. The activities of peroxisome proliferator activated receptor
      alpha (PPARalpha) in the myocardium were also observed. Rosiglitazone/Metformin
      decreased body weight gain and food intake, and inhibited an increasing adipose
      ratio but did not reduce myocardial hypertrophy. Rosiglitazone increased
      Kir6.2/SUR2A, Kir6.2/SUR2B, and PPARalpha gene expression. The
      Rosiglitazone/Metformin combination further increased these gene expressions,
      especially PPARalpha. Metformin inhibits obesity but has no effect in reducing
      myocardial hypertrophy caused by Rosiglitazone. Whether Metformin can reduce side
      effects of TZDs in humans warrants further study.

PMID- 20823566
TI  - Antidiabetic effect and mechanism of chitooligosaccharides.
AB  - The aim of this study was to observe the antidiabetic effect and mechanism of
      chitooligosaccharides (COS). Type 2 diabetic rats were fed a high-energy diet
      together with an injection of streptozotocin (STZ). After 8 weeks of COS
      treatment, the changes in glycometabolism, insulin sensitivity, serum hepatic
      marker enzyme levels, liver glycogen content, expressions of glucose transporter
      GLUT-4, malonaldehyde content, superoxide dismutase activity and morphology of
      the pancreas were observed. The results showed that COS significantly reduced
      fasting blood glucose (FBG), fasting insulin (FINS), increased the insulin
      sensitivity index (ISI) and improved oral glucose tolerance. COS increased liver
      glucokinase activity and glycogen content and upregulated the expressions of GLUT
      4 mRNA in adipose and soleus muscle. They also raised the superoxide dismutase
      activity and reduced the malonaldehyde content in pancreas homogenate. Pancreas
      hematoxylin/eosin (HE) staining of the diabetic rats showed ruptured islet, but
      changes of pancreatic islet in the animals were minimized by administration of
      COS. The effect of COS on pancreatic beta cell (INS-1) in vitro was also
      examined. It was found that COS played important roles in INS-1 cells by
      promoting proliferation, increasing glucose stimulated insulin release,
      upregulating the expressions of GLUT-2 mRNA and protecting against STZ-induced
      apoptosis. The results from the present study indicate COS have protective effect
      for type 2 diabetes by ameliorating insulin resistance, promoting the
      proliferation of beta cells, increasing insulin secretion and protecting beta
      cells.

PMID- 20823567
TI  - Effects of captopril and telmisartan on matrix metalloproteinase-2 and -9
      expressions and development of left ventricular fibrosis induced by isoprenaline
      in rats.
AB  - The aim of this study was to clarify the effects of renin-angiotensin system
      (RAS) blockade by captopril, an angiotensin converting enzyme inhibitor, and
      telmisartan, an angiotensin II type 1 receptor antagonist, on matrix
      metalloproteinase (MMP)-2 and MMP-9 expressions and development of left
      ventricular (LV) fibrosis induced by isoprenaline in rats. Rats were treated with
      subcutaneous injection of isoprenaline (5 mg/kg/d) and with oral administration
      of captopril (30 mg/kg/d) or telmisartan (3 mg/kg/d) for 1 or 7 d. Hearts were
      excised at the day 2 and day 8. Degree of fibrosis was evaluated by Azan
      staining. MMP-2 and MMP-9 expressions were analyzed by Western blotting.
      Localization of MMP-9 expression in LV section was detected by
      immunohistochemical staining. At the day 8, myocardial fibrosis was observed in
      LV section from isoprenaline-treated rats. Captopril but not telmisartan
      significantly enhanced the isoprenaline-induced myocardial fibrosis. MMP-9
      expression at the day 2 and MMP-2 expression at the day 8 increased significantly
      in LV from isoprenaline-treated rats. Captopril had no influence on the MMP-2
      expression, but significantly augmented the isoprenaline-induced MMP-9
      expression. Telmisartan had no effect on the isoprenaline-induced MMP-2 and MMP-9
      expressions. In immunohistochemical staining, MMP-9 positive-interstitial cells
      were extensively observed in LV sections from isoprenaline + captopril-treated
      rats at the day 2. The present study reveals that RAS blockade by captopril and
      telmisartan does not have suppressive effects on isoprenaline-induced MMP-2 and
      MMP-9 expressions as well as LV fibrosis. Furthermore, captopril may enhance LV
      fibrosis through promoting isoprenaline-induced MMP-9 expression in cardiac
      interstitial cells.

PMID- 20823568
TI  - Effects of combination treatment with dexamethasone and mannitol on neuronal
      damage and survival in experimental heat stroke.
AB  - There is evidence that increased plasma cytokines, elevated brain levels of
      monoamines and hydroxyl radical production may be implicated in pathogenesis
      during heat stroke in rats. Acute treatment with a combined therapeutic approach
      has been repeatedly advocated in cerebral ischemia experiments. The aim of this
      study was to investigate whether the combined agent (mannitol and dexamethasone)
      has beneficial efficacy to improve the survival time (ST) and heat stroke-induced
      damage in experimental heat stroke. Urethane-anesthetized rats underwent
      instrumentation for the measurement of colonic temperature, mean arterial
      pressure (MAP), striatal cerebral blood flow (CBF), heart rate, and neuronal
      damage score. The rats were exposed to an ambient temperature (43 degrees C) to
      induce heat stroke. Concentrations of the ischemic and damage markers, dopamine,
      serotonin, and hydroxyl radical production in corpus striatum, and the plasma
      levels of tumor necrosis factor-alpha (TNF-alpha) were observed during heat
      stroke. After the onset of heat stroke, the heat stroke rats display decreased
      MAP, decreased CBF, increased the plasma levels of TNF-alpha, increased cerebral
      striatal monoamines and hydroxyl radical production release, and severe cerebral
      ischemia and neuronal damage compared with those of normothermic control rats.
      However, immediate treatment with the combined agent confers significant
      protection against heat stroke-induced arterial hypotension, systemic
      inflammation, cerebral ischemia, cerebral monoamines and hydroxyl radical
      production overloads, and improves neuronal damage and the ST in heat stroke
      rats. Our data suggest that administration of this combined agent seems to have
      more effective to ameliorate the heat stroke-induced neuronal damage and prolong
      the ST.

PMID- 20823569
TI  - 3-O-demethylswertipunicoside protects against oxidative toxicity in PC12 cells.
AB  - Xanthone compounds have been reported to inhibit cancer cell growth as well as
      possessing antioxidant properties. The xanthone compound 3-O
      demethylswertipunicoside (3-ODS), extracted from Swertia punicea HEMSL, has not
      previously been demonstrated to have clear neuroprotective effects. In our study,
      the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell death
      assay revealed that treatment of PC12 cells with 3-ODS ameliorated the decreased
      cell viability induced by exposure to 1-methyl-4-phenylpyridinium ion (MPP+),
      rotenone or H2O2. The acridine orange/ethidium bromide (AO/EB) apoptosis assay
      demonstrated a significant suppression of cell death in PC12 cells. by 3-ODS
      treatment. 3-ODS increased the protein expression of both tyrosine hydroxylase
      (TH) and DJ-1 expression in PC12 cells. The current study demonstrates that 3-ODS
      has potential neuroprotective effects mediated via the elevation of TH and DJ-1
      protein levels.

PMID- 20823570
TI  - The natural flavonoid quercetin ameliorates cerulein-induced acute pancreatitis
      in mice.
AB  - Many plant-derived flavonoids including quercetin exhibit antioxidant and
      antiinflammatory properties. Proinflammatory cytokines and oxidative stress play
      an important role in acute pancreatitis. This study aimed to evaluate the effect
      of quercetin on cerulein-induced acute pancreatitis in mice. Animal groups were
      pretreated with quercetin (25, 50, 100 mg/kg, per os (p.o.)), thalidomide (200
      mg/kg, p.o.) or vehicle (2% dimethyl sulfoxide (DMSO)) 1 h before hourly (x5)
      intraperitoneal injections of cerulein. A saline (0.9%, NaCl)-treated control
      group was included for comparison. Cerulein significantly enhanced the serum
      levels of amylase and lipase, and pancreatic myeloperoxidase activities,
      malondialdehyde and the proinflammatory cytokines tumor necrosis factor-alpha
      (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6, as well as the pancreatic
      wet weight/body weight ratio. Cerulein significantly reduced the serum levels of
      IL-10. Histological assessment of the pancreas showed tissue edema, neutrophil
      infiltration, acinar vacuolization, and cell necrosis and a marked increase in
      the immunoreactivity staining for TNF-alpha. Pretreatment with quercetin or
      thalidomide significantly attenuated the severity of cerulein-induced acute
      pancreatitis as evidenced by effective reductions in the pancreatic wet
      weight/body weight ratio, biochemical indices, proinflammatory cytokines,
      myeloperoxidase activity, malondialdehyde formation, and an increase in
      antiinflammatory cytokine IL-10. Quercetin treatment also markedly suppressed the
      histological changes such as pancreatic edema, inflammatory cell infiltration,
      acinar cell necrosis, and the expression of TNF-alpha. Taken together, these
      results indicate that quercetin ameliorates the severity of cerulein-induced
      acute pancreatitis by acting as an antiinflammatory and antioxidant agent.

PMID- 20823571
TI  - Optimized PEGylated adenovirus vector reduces the anti-vector humoral immune
      response against adenovirus and induces a therapeutic effect against metastatic
      lung cancer.
AB  - Application of adenovirus vectors (Adv) in metastatic cancer treatment is
      limited. We previously demonstrated that covalent conjugation of
      polyethleneglycol (PEG) to Adv enhances therapeutic effects and decreases toxic
      side-effects after systemic administration, but the level of immune response to
      PEGylated Adv (PEG-Ad) was not examined. Here, we examined the effect of
      PEGylation of Adv on the production of anti-Adv antibodies and antitumor
      response. We constructed a set of PEG-Ad using 5-kDa PEG, with modification rates
      of 30%, 45% and 90%. After systemic administration of Advs to rats, we examined
      the level of anti-Adv immunoglobulin (Ig)G and IgM in serum. The levels of anti
      Adv IgG and anti-Adv IgM in rats treated with unmodified Adv were higher than
      those in control group. Rats treated with PEG-Ad that had a 90% modification rate
      showed lower level of anti-Adv IgG and anti-Adv IgM than those treated with
      unmodified Adv, whereas rats treated with PEG-Ad that had a 30% or 45%
      modification rate showed a similar level of anti-Adv IgG and IgM to those treated
      with unmodified Adv. Systemic administration of PEG-Ad that had a 90%
      modification rate, and expressed tumor necrosis factor-alpha, significantly
      reduced the number of metastatic colonies in the lung compared to unmodified Adv,
      with negligible side effects. These results suggest that systemic administration
      of PEG-Ad with an appropriate PEG modification rate has the potential to reduce
      the production of antibodies against Adv and increase the therapeutic response
      against metastatic cancer.

PMID- 20823572
TI  - Specific alternation of rhythm in temperature (SART) stress-induced irritable
      bowel syndrome-like changes in mice and effects of drugs.
AB  - Stress is closely associated with the manifestation and progress of irritable
      bowel syndrome (IBS). For the purpose of establishing experimentally the
      relationship between IBS and stress, the transportation capacity of the small
      intestine in specific alternation of rhythm in temperature (SART)-stressed
      animals was studied using charcoal transportation method. The charcoal suspension
      was administered orally into the stomach of fasting mice. Mice were sacrificed
      after a certain time and %charcoal transit (%CT) of the small intestine was
      measured. The %CTs in SART-stressed mice were greater than those in unstressed or
      continuously cold-stressed mice. This increase in %CT remained for 1 week after
      discontinuation of SART stress loading. Cholinergic blockers decreased %CTs in
      SART-stressed mice. Increases in %CT by a cholinesterase inhibitor were less in
      SART-stressed mice than in unstressed mice. Increases of %CT in SART-stressed
      mice were suppressed by Neurotropine. These results suggested that the
      parasympathetic hypertonicity, not just cold, played a role in the increases in
      the transportation capacity in SART-stressed mice and that these animals can be a
      useful tool for elucidation of the mechanism of IBS.

PMID- 20823573
TI  - Hypoxia-inducible factor-1alpha is involved in the pro-angiogenic effect of
      hydrogen sulfide under hypoxic stress.
AB  - Hydrogen sulfide (H2S) is known to have pro-angiogenic properties in mammals. In
      this study, we examined H2S played the role in pro-angiogenesis mediated by
      hypoxia-inducible factor (HIF)-1alpha under hypoxic conditions. Rat brain
      capillary endothelial cells (ECs) were treated with NaHS (a H2S donor) pretreated
      vascular smooth muscle cells (VSMCs) conditioned media. ECs proliferation was
      evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      assay. ECs migration was assessed by chemotaxis chamber assay. Angiogenesis
      associated gene expression levels were determined by reverse transcription
      polymerase chain reaction (RT-PCR). HIF-1alpha and vascular endothelial growth
      factor (VEGF) accumulation was analyzed by Western blotting. HIF-1 binding
      activity was measured by electrophoretic mobility shift assay (EMSA). We found
      H2S induced both endothelial proliferation and migration in mimic hypoxic
      condition. In addition, H2S promoted VEGF and HIF-1alpha mRNA levels. H2S also
      significantly upregulated HIF-1alpha and VEGF protein levels and increased HIF
      1alpha binding activity under hypoxic condition. Our findings suggest that HIF
      1/VEGF is involved in H2S promotes proliferation and migration of ECs.

PMID- 20823574
TI  - Vasorelaxant activity of Sappan Lignum constituents and extracts on rat aorta and
      mesenteric artery.
AB  - We investigated the vasorelaxant activity of the methanolic extracts of Sappan
      Lignum (CSE) and its constituents, brazilin, sappanchalcone, and protosappanins A
      E, on rat aorta and mesenteric artery. By comparing the vasorelaxant activity of
      CSE and brazilin on both blood vessels, we found that CSE contained active
      constituents other than brazilin. When added to brazilin, sappanchalcone and
      protosappanin D showed vasorelaxant activity on both blood vessels precontracted
      with phenylephrine. We clarified that the vasorelaxant activity of brazilin was
      endothelium-independent, while that of sappanchalcone was endothelium-dependent,
      on both blood vessels. On the other hand, the vasorelaxant activity of
      protosappanin D was independent of the endothelium of the aorta and dependent on
      the endothelium of the mesenteric artery. Experiments on sappanchalcone and
      protosappanin D using NG-nitro-L-arginine and indomethacin revealed the
      involvement of nitric oxide and prostaglandin as endothelium-derived relaxation
      factors (EDRFs). The anti-oketsu effect of Sappan Lignum might be attributable to
      the interaction of those compounds. We could partly evaluate the anti-oketsu
      activity of Sappan Lignum using both the aorta and the mesenteric artery. Through
      this study, we showed the importance of comparing the effects on the aorta and
      the mesenteric artery as we found that natural compounds showed different
      mechanisms of action on the two blood vessels.

PMID- 20823576
TI  - Regulation of monocarboxylate transporter 1 in skeletal muscle cells by
      intracellular signaling pathways.
AB  - Skeletal muscle is the major producer of lactic acid in the body, but its
      oxidative fibers also use lactic acid as a respiratory fuel. Monocarboxylate
      transporter (MCT) 1 has been suggested to play a major role in influx of L-lactic
      acid for oxidation. The regulation mechanism of MCT1 was characterized utilizing
      rhabdomyosarcoma cells as an in vitro skeletal muscle model. The uptake of L
      lactic acid via MCT1 was studied in the presence of various intracellular
      regulatory pathways, including pathways mediated by protein kinases A, C and G
      (PKA, PKC and PKG), protein tyrosine kinase (PTK), and Ca2+/calmodulin
      modulators. The results showed that PKG-, PTK-, and Ca2+/calmodulin-mediated
      regulatory pathways play no role in the regulation of L-lactic acid uptake, but a
      role for PKC- and PKA-mediated pathways was apparent. Uptake of L-lactic acid
      appeared to be stimulated by phorbol 12-myristate 13-acetate (PMA, a PKC
      activator) via an increase in Vmax of transport processes with no alteration in
      Km. In parallel, PMA treatment also resulted in an increase in the level of MCT1
      expression. On the other hand, exposure to 8-Br-cAMP, a cAMP analog, and to
      forskolin, an adenylyl cyclase activator, resulted in a significant decrease in L
      lactic acid uptake. Additionally, 8-Br-cAMP reduced Vmax but not Km values.
      Parallel to the decrease in Vmax of L-lactic acid uptake, the level of MCT1
      expression was decreased in response to incubation with 8-Br-cAMP. These results
      indicate the possible involvement of a PKC- and PKA-mediated pathway associated
      with expression of MCT1 and lactate transport.

PMID- 20823575
TI  - Oral sustained release tablets of zidovudine using binary blends of natural and
      synthetic polymers.
AB  - Oral sustained release matrix tablets of zidovudine (ZDV) were prepared using
      different types, proportions and blends of carbopol 71G (C71) and a plant gum
      obtained from Abelmoschus esculentus (AEG). The effect of various formulation
      factors like polymer proportion, polymer type and pH of the dissolution medium on
      the in vitro release of the drug was studied, using the half change technique, in
      900 ml of dissolution medium, at 100 rpm. Release kinetics were analyzed using
      Zero-order, Higuchi's square-root and Ritger-Peppas' empirical equations. In
      vitro release performance as revealed by the time taken for 70% of the drug to be
      released (t70%), showed that the release rate decreased with increase in polymer
      proportion. Matrix tablets containing 10 and 20% AEG were found to exhibit
      immediate-release characteristics. Matrix tablets containing 30% AEG showed t70%
      value of 204 min and extended the release up to 5 h, while matrix tablets
      containing 30% carbopol showed t70% value of 234 min and extended the release up
      to 6 h. Three blends of AEG and C71 at the ratio of 1:2, 2:1 and 1:3 showed t70%
      values of 132, 312 and 102 min respectively and extended the release up to 8 h.
      Mathematical analysis of the release kinetics indicated that the nature of drug
      release from the matrix tablets followed Fickian and anomalous release. Drug
      release from matrix tablets of zidovudine containing blends of AEG and C71
      demonstrates the advantage of blending a natural and synthetic polymer over
      single polymer use.

PMID- 20823577
TI  - Reduction in intraocular pressure by the instillation of eye drops containing
      disulfiram included with 2-hydroxypropyl-beta-cyclodextrin in rabbit.
AB  - We have studied the effect of disulfiram (DSF) solution containing 2
      hydroxypropyl-beta-cyclodextrin and hydroxypropylmethylcellulose (DSF eye drops)
      on intraocular pressure (IOP) in experimentally induced ocular hypertension in
      rabbits. In both in vitro and in vivo transcorneal penetration experiments using
      rabbit corneas, only diethyldithiocarbamate (DDC) was detected in the aqueous
      humor, while DSF was not detected. The amount of DDC penetration for 0.25% DSF
      eye drops was about 4-fold that for 0.1% DSF eye drops in in vivo transcorneal
      penetration experiments. The elevation in IOP was induced by the rapid infusion
      of 5% glucose solution (15 ml/kg of body weight) through the marginal ear vein,
      and IOP was measured with an electronic tonometer. The induced elevation in IOP
      was reduced by the instillation of 0.1-0.5% DSF eye drops, and the IOP-reducing
      effect increased with the increase in DSF concentration in the drops. Nitric
      oxide (NO) levels increased in the aqueous humor following the infusion of the 5%
      glucose solution, and this increase was also suppressed by the instillation of
      DSF eye drops. In conclusion, the present study demonstrates that the
      instillation of DSF eye drops has an IOP-reducing effect in rabbits with
      experimentally induced ocular hypertension, probably caused by the suppression of
      NO production.

PMID- 20823578
TI  - Construction of genomic DNA library of Korean ginseng (Panax ginseng C. A. MEYER)
      and development of sequence-tagged sites.
AB  - This study describes an efficient approach for developing sequence tagged sites
      (STS) for Panax ginseng C.A. MEYER, and their applications for line
      discrimination. By using the methylation filtering (MF) technique, a genomic
      library was constructed, in which clone inserts were derived from the
      hypomethylated regions of ginseng genome. A methylation unfiltered genomic
      library was also constructed and the clone inserts were compared to those from
      the MF library in terms of sequence characteristics. Sequence analysis revealed
      that MF efficiently enriched the protein coding region of P. ginseng, for which
      the repetitive DNA appeared to be as little as 2.5 fold lower than clones in the
      unfiltered library, and also indicated that the P. ginseng genome may contain a
      large fraction of methylated repetitive DNA elements. A total of 99 and 100
      highly stringent STS primer sets were designed from the filtered and unfiltered
      library, respectively. Amplification products were tested for latent polymorphism
      across six cultivars of P. ginseng and other 2 Panax species using six
      endonucleases recognizing four-bases. STS primer sets described here will be
      useful for marker-assisted selection, genome mapping and line discrimination of
      P. ginseng or its cultivars from other Panax species.

PMID- 20823579
TI  - Radioimmunodetection of membrane type-1 matrix metalloproteinase relevant to
      tumor malignancy with a pre-targeting method.
AB  - Since membrane type-1 matrix metalloproteinase (MT1-MMP) is exclusively expressed
      in tumors and is closely associated with metastasis and invasion, MT1-MMP is a
      potential target of radiotracers for the evaluation of tumor malignancy. In this
      study, we planned to visualize MT1-MMP in vivo by a two-step pre-targeting
      strategy using a streptavidin (SAv)-biotin system combined with anti-MT1-MMP
      monoclonal immunoglobulin (IgG) (anti-MT1-MMP monoclonal antibody (mAb)).
      Streptavidinylated anti-MT1-MMP mAb was synthesized by reacting biotinylated anti
      MT1-MMP mAb with SAv. In the pre-targeting study, FM3A mouse breast carcinoma
      implanted mice were injected with anti-MT1-MMP mAb-SAv, followed 72 h later with
      radioiodinated biotin, (3-[123/125I]iodobenzoyl)norbiotinamide (123/125I-IBB).
      Biodistribution and imaging (single photon emission computed tomography
      (SPECT)/CT) data were collected at several time points in the 24 h period
      following introduction of the tracer. The comparison groups were injected with
      125I-IBB alone or with 125I-IBB pre-targeted with negative control IgG-SAv. In
      the pre-targeting study for MT1-MMP, within 1 h of tracer injection, rapid tumor
      uptake and abrupt clearance from the blood of radioactivity (2.22, 0.87% injected
      dose/g at 1 h) were observed. The tumor to blood (T/B) radioactivity ratios were
      significantly higher than those from mice dosed with the pre-targeting negative
      control (p<0.0001). 125I-IBB alone did not accumulate in tumors. SPECT/CT image
      analysis of FM3A bearing mice showed high-contrast tumor images after 3 h with
      minimal blood-pool activity. The present study that uses a pre-targeting method
      showed high T/B radioactivity ratios and clear tumor images of MT1-MMP. This
      imaging method may be useful for the clinical diagnosis of malignant tumors.

PMID- 20823580
TI  - Measurement of sialic acid content is insufficient to assess bioactivity of
      recombinant human erythropoietin.
AB  - Assessment of biological potency and its comparison with clinical effects are
      important in the quality control of therapeutic glycoproteins. Animal models are
      usually used for evaluating bioactivity of these compounds. However, alternative
      methods are required to simplify the bioassay and avoid ethical issues associated
      with animal studies. Negatively charged sialic acid residues are known to be
      critical for in vivo bioactivity of recombinant human erythropoietin (rhEPO). In
      this study, we used capillary zone electrophoresis, a charge-based separation
      method, to estimate the sialic acid content for predicting in vivo bioactivity of
      rhEPO. In vivo bioactivities of rhEPO subfractions were measured and compared
      with sialylation levels. The results obtained indicated that in vivo bioactivity
      of rhEPO is not simply correlated with the sialylation level, which suggests that
      it is difficult to predict biological potency from the sialic acid content alone.
      N-Glycan moieties as well as sialic acid residues may have a significant impact
      on in vivo bioactivity of rhEPO.

PMID- 20823581
TI  - Discovery of phosphatidylinositol 3-kinase inhibitory compounds from the
      Screening Committee of Anticancer Drugs (SCADS) library.
AB  - Identification of new uses for existing drugs is known to be an efficient
      approach in drug discovery. The identification of a novel phosphatidylinositol 3
      kinase (PI3K) inhibitor is important in terms of cancer chemotherapy because PI3K
      is implicated in many types of cancer. In an effort to discover new PI3K
      inhibitory compounds, we recently carried out a screening of Screening Committee
      of Anticancer Drugs (SCADS) library, a compound library mainly composed of
      antitumor drugs and kinase inhibitors. As a result, six new PI3K inhibitory
      compounds were identified each of which displayed over 60% inhibition of
      PI3Kalpha at 10 microM. Baicalein, the most potent of these inhibitors, exhibited
      73% inhibition at 1 microM. Further characterization of Baicalein and Akt
      inhibitor VIII showed that both compounds displayed comparable inhibition against
      PI3Kbeta and delta, but relatively weak activity against PI3Kgamma. Growth
      inhibition effects of Akt inhibitor VIII and Baicalein on human cancer cell line
      panel JFCR39 were also investigated, and the mean logarithm of the concentration
      required for 50% growth inhibition of cells (Log GI50) was determined to be -5.59
      and -4.70, respectively. In addition, COMPARE analysis of the two compounds
      together with known PI3K inhibitors was carried out by using PI3K inhibitor
      ZSTK474 as a seed. Our results show that Akt inhibitor VIII displays a similar
      fingerprint to that of ZSTK474 (r=0.633), while Baicalein does not (r=0.126).
      These findings suggest the inhibition profile of Baicalein in cells is different
      from that of a typical PI3K inhibitor.

PMID- 20823582
TI  - Inhibition of aldose reductase and xylose-induced lens opacity by puerariafuran
      from the roots of Pueraria lobata.
AB  - High sugar levels found in diabetic cataract cause the opacification of lenses by
      osmotic changes induced via the aldose reductase (AR)-mediated polyol pathway. In
      this study, puerariafuran, a 2-arylbenzofuran from Pueraria lobata, investigated
      the inhibitory effects upon AR, antioxidant contents and enzyme activities in the
      lens. The effect of puerariafuran on xylose-induced lens opacity was also
      examined. Puerariafuran showed potential inhibitory activity with an IC50 value
      of 22.34 microM against rat lens AR. The xylose-induced opacity of lenses was
      significantly improved when treated with puerariafuran. Xylose exposure of rat
      lenses significantly decreased the reduced glutathione (GSH)/oxidized glutathione
      (GSSG) ratio, superoxide dismutase (SOD), and catalase (CAT) activity and
      treatment with puerariafuran significantly increased these factors. These results
      suggest that puerariafuran may provide a potential therapeutic approach for
      prevention of diabetic complications, such as cataracts.

PMID- 20823583
TI  - Inhibitory effects of coumarins from the stem barks of Fraxinus rhynchophylla on
      adipocyte differentiation in 3T3-L1 cells.
AB  - In the course of screening anti-adipogenic activity of natural products employing
      the preadipocyte cell line, 3T3-L1 as an in vitro assay system, the EtOAc
      fraction of the stem barks of Fraxinus rhynchophylla DENCE (Oleaceae) showed
      significant inhibitory activity on adipocyte differentiation as assessed by
      measuring fat accumulation using Oil Red O staining. Activity-guided
      fractionation led to the isolation of six coumarins such as esculetin (1),
      scopoletin (2), fraxetin (3), fraxidin (4) esculin (5) and fraxin (6). Among the
      six coumarins isolated, esculetin (1) showed the most potent inhibitory activity
      on adipocyte differentiation, followed by fraxetin (3). Further studies with
      interval treatment demonstrated that esculetin (1) exerted inhibitory activity on
      adipocyte differentiation when treated within 2 d (days 0-2) after
      differentiation induction. We further investigated the effect of esculetin (1) on
      peroxisome proliferator activated receptor gamma (PPARgamma), one of the early
      adipogenic transcription factors. Esculetin (1) significantly blocked the
      induction of PPARgamma protein expression and inhibited adipocyte differentiation
      induced by troglitazone, a PPARgamma agonist. Taken together, these results
      suggest that esculetin (1), an active compound from F. rhynchophylla, inhibited
      early stage of adipogenic differentiation, in part, via inhibition of PPARgamma
      dependent pathway.

PMID- 20823584
TI  - Effects of quercetin on human alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid receptor-mediated ion currents.
AB  - Quercetin is a low molecular weight flavonoid found in dietary fruits and
      vegetables. Quercetin, like other flavonoids, has demonstrated neuroprotective
      effects in vitro and in vivo. However, relatively little is known about how
      quercetin achieves its neuroprotective abilities. The alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) receptor is one of several excitatory
      receptors, which play an important role in postsynaptic neurotransmission. Over
      stimulation of ionotropic glutamate receptor including AMPA receptors is closely
      associated with excitatory neurotoxicities. In the present study, we investigated
      the effects of quercetin on the glutamate-induced inward current (IGlu) in
      Xenopus oocytes that heterologously express human AMPA receptor and stargazin, an
      auxiliary subunit of AMPA receptor. IGlu was measured using the two-electrode
      voltage clamp technique. In oocytes injected with cRNAs coding AMPA receptor
      (GluR1) and stargazin, quercetin inhibited IGlu in a reversible and concentration
      dependent manner. The IC50 was 84.9+/-15.0 microM. Quercetin action on IGlu was
      attenuated by increasing glutamate concentration, and was membrane holding
      potential-dependent. These results show a possibility that quercetin interacts
      with AMPA receptor, which was heterologously expressed in Xenopus oocytes and
      that quercetin action on IGlu of AMPA receptor could be one of contributions of
      quercetin-mediated neuroprotections.

PMID- 20823585
TI  - 3alpha,23-isopropylidenedioxyolean-12-en-27-oic acid, a triterpene isolated from
      Aceriphyllum rossii, induces apoptosis in human cervical cancer HeLa cells
      through mitochondrial dysfunction and endoplasmic reticulum stress.
AB  - In the present study, we investigated the effect of 3alpha,23
      isopropylidenedioxyolean-12-en-27-oic acid (IPA), an active compound isolated
      from Aceriphyllum rossii, on the apoptotic activity and the molecular mechanism
      of the action in human cervical cancer HeLa cells. Treatment with IPA
      significantly increased externalization of phosphatidylserine residues and
      apoptotic DNA fragmentation as shown by Annexin V staining and 4',6-diamidino-2
      phenylindole-dihydrochloride (DAPI) staining, respectively. In addition, IPA
      induced the activations of caspase-8, -9, -3, and cleavage of poly(ADP ribose)
      polymerase (PARP-1) in HeLa cells. Pretreatment with a specific caspase-8, -9, or
      -3 inhibitor neutralized the pro-apoptotic activity of IPA in HeLa cells.
      Furthermore, IPA was found to induce the loss of mitochondrial membrane
      potential, the release of cytochrome c to the cytosol, and the increased ratio of
      mitochondrial Bax/Bcl-2. Moreover, we demonstrated that IPA triggered endoplasmic
      reticulum (ER) stress, as shown by changes in cytosol-calcium level, activation
      of mu-calpain and caspase-12, and up-regulation of glucose-regulated protein 78
      (GRP78) and growth arrest DNA damage-inducible gene 153 (GADD153). IPA-induced
      apoptosis was substantially reduced in the presence of an intracellular calcium
      chelator BAPTA/AM. Taken together, these results suggest that both mitochondrial
      dysfunction and ER stress contribute to IPA-induced apoptosis of human cervical
      cancer HeLa cells.

PMID- 20823586
TI  - Key physiological phenomena governing transgene expression based on tissue
      pressure-mediated transfection in mice.
AB  - It is generally recognized that in vivo gene transfection is one of the most
      important techniques used in the post-genome era. Above all, naked plasmid DNA
      transfection has attracted much attention because of its advantages including
      convenience of preparation and handling and lack of toxicity associated with the
      transfection agents. We have investigated tissue pressure-mediated transfection
      performed by light and controlled pressure of the target tissue after normal
      intravenous injection of plasmid DNA. So far, we have demonstrated that plasmid
      DNA and small-interfering RNA (siRNA) are very efficiently transfected into
      murine kidney, liver and spleen without causing marked tissue damage. In this
      study, in order to understand the key physiological phenomena affecting transgene
      expression, we performed a set of experiments involving tissue pressure-mediated
      transfection, including the biodistribution and cellular transport of plasmid DNA
      and activation of transcriptional factors and obtained the following results: i)
      plasmid DNA transfer to the target tissue and its cells increased although the
      transferred fraction was small compared to the total administered plasmid DNA,
      ii) a transient increase in cellular translocation of plasmid DNA was induced,
      and iii) transcriptional factors were activated. Taking all these results into
      consideration, it would appear that tissue pressure-mediated transfection
      enhances plasmid DNA transfer to the target tissue and its cells and also
      activation of the transcriptional process. This information will allow a better
      understanding of in vivo transgene expression based on naked plasmid DNA
      transfection involving tissue pressure-mediated transfection.

PMID- 20823587
TI  - Inhibitory effects of nitrative stress on the sulfation of 17beta-estradiol and 4
      methoxyestradiol by human MCF 10A mammary epithelial cells.
AB  - Prolonged exposure to high level of estrogen is a known risk factor for breast
      carcinogenesis. It has been suggested recently that nitrative stress may be an
      etiologic factor for breast carcinogenesis. Since sulfation plays a major role in
      the homeostasis of estrogens and their metabolites, we attempted in the present
      study to find out whether nitrative stress may affect the homeostasis of
      estrogens through sulfation. Metabolic labeling experiments revealed that the
      amount of sulfated 17beta-estradiol or 4-methoxyestradiol decreased dramatically
      in MCF-10A mammary epithelial cells incubated in the presence of 3
      morpholinosydnonimine (SIN-1) or diethylenetriamine NONOate (DETA NONOate), two
      nitric oxide donors commonly used to simulate nitrative stress conditions. In
      searching for the mechanism underlying the decrease of the sulfation of 17beta
      estradiol and 4-methoxyestradiol, we demonstrated in an in vitro nitration
      experiment, that the human cytosolic sulfotransferase isoform 1E1 (SULT1E1), a
      major estrogen-sulfating enzyme, lost its estrogen-sulfating activity
      proportionately to the degree of nitration on tyrosine residues. Moreover, cell
      lysates prepared from MCF-10A cells treated with SIN-1 or DETA NONOate also
      showed much lower 4-methoxyestradiol-sulfating activities, compared with those
      determined with cell lysate prepared from control MCF-10A cells.

PMID- 20823588
TI  - Design, synthesis and biological evaluation of 3-(4-halophenyl)-3-oxopropanal and
      their derivatives as novel antibacterial agents.
AB  - In continuing our program aimed to search for potent drugs for bacterial
      infections, a series of 3-(4-halophenyl)-3-oxopropanal and their derivatives were
      designed, synthesized and their antibacterial activities in vitro against both
      Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria
      Escherichia coli and Pseudomonas aeruginosa were evaluated. Compounds 7, 8, 13
      16, 21 and 22 had moderate antibacterial activities against Staphylococcus aureus
      (minimal inhibitory concentration (MIC) <16 microg/ml), suggesting that the
      introduction of mono-methoxyamine or ethoxyamine moiety might play an important
      role in determining the potent antibacterial activities. Furthermore, the
      antibacterial activities of select compounds 7, 15 and 16 against the clinically
      important pathogenic bacteria-methicillin-resistant Staphylococcus aureus (MRSA)
      were also investigated. Results showed that these compounds exhibited more potent
      activities than the well-known antibacterial agents Houttuynin and Levofloxacin.

PMID- 20823589
TI  - Solubility of pioglitazone hydrochloride in binary mixtures of polyethylene
      glycol 400 with ethanol, propylene glycol, N-methyl-2-pyrrolidone, and water at
      25 degrees C.
AB  - The solubility of pioglitazone hydrochloride in binary mixtures of polyethylene
      glycol 400 with ethanol, N-methyl-2-pyrrolidone, propylene glycol, and water at
      25 degrees C are reported. The generated data are fitted to the Jouyban-Acree
      model and the mean relative deviations are 2.6%, 1.5%, 5.8%, and 7.4%,
      respectively for ethanol, N-methyl-2-pyrrolidone, propylene glycol, and water.

PMID- 20823590
TI  - Nateglinide controlled release tablet containing compressionable enteric coated
      granules.
AB  - We designed a single unit type controlled release tablet containing nateglinide
      to decrease both postprandial blood glucose level (PBG) and fasting blood glucose
      level (FBG) in normal beagle dogs. The tablet contains 60 mg of nateglinide in an
      immediate release portion, and 90 mg of nateglinide in a controlled release
      portion. Compressionable enteric coated granules were selected as the controlled
      release portion to primarily decrease FBG, and they were prepared by an aqueous
      coating with Eudragit. Three types of nateglinide controlled release tablets were
      obtained, and their weights were 418.1-425.1 mg/tablet containing the above
      compressionable enteric coated granules. Even after tableting, the dissolution
      behavior of enteric coated granules was maintained approximately. In vivo single
      oral administration studies using normal male beagle dogs demonstrated that these
      tablets were able to decrease both PBG and FBG. The relative bioavailability
      values of the obtained tablets containing enteric coated granules having a
      dissolution pH of 6.0 and 6.8 were estimated at about 57.2 and 60.8% respectively
      against nateglinide immediate release tablets. In an in vivo repeated
      administration study with the tablets containing enteric coated granules having a
      dissolution pH of 6.8 (an interval: 8 h), decreases in both PBG and FBG were
      observed continuously twice. On the basis of the above results, it is expected to
      enable control of both PBG and FBG for moderate and severe diabetes patients with
      a controlled release formulation containing a short-acting type oral blood
      glucose regulator, not only nateglinide but also meglitinides (repaglinide,
      mitiglinide, etc.).

PMID- 20823591
TI  - Treatment of rat brain tumors using sustained-release of camptothecin from
      poly(lactic-co-glycolic acid) microspheres in a thermoreversible hydrogel.
AB  - A thermoreversible gelation polymer consisting of an aqueous solution in the sol
      state at room temperature and in the gel state near body temperature was examined
      for its use in the retention of microspheres and sustained, long-term delivery of
      anti-cancer drugs using a rat model of malignant glioma. The poly(lactic-co
      glycolic acid) (PLGA) microspheres containing camptothecin at ratios of 1 : 33 or
      1 : 50 mediated sustained release, with approximate 80% of camptothecin released
      after 28 d. Rats were inoculated in the brain with C6 glioma cells, followed 7 d
      later by injection in the tumor site with 1 : 33 and 1 : 50 PLGA microspheres
      dispersed in a thermoreversible gelation polymer (TGP) solution. Kaplan-Meier
      analysis showed that the mean survival period of the untreated group was 16 d,
      with a slight increase in rats treated with TGP-only solution, empty or 1 : 50
      microspheres in phosphate-buffered saline. The mean survival period of rats
      treated with the camptothecin powder in TGP was 21 d, while that of rats treated
      with 1 : 33 and 1 : 50 microspheres in TGP was significantly longer than the
      untreated group; long-term survival rats were observed. These results suggest
      that the anti-tumor effect of camptothecin can be enhanced by long-term sustained
      release from microspheres retained in the rat brain by TGP gel.

PMID- 20823592
TI  - Synthesis and anticonvulsant activity of certain substituted furochromone,
      benzofuran and flavone derivatives.
AB  - Synthesis of furochromone, 2-phenylchromone (flavone) and benzofuran derivatives
      substituted with thiosemicarbazide or thiazolidin-4-one moieties were
      accomplished. All the newly synthesized compounds were tested for their
      anticonvulsant activity in both subcutaneous pentylenetetrazole induced seizures
      (scPTZ) and maximal electric shock induced seizures (MES) tests using valproic
      acid and phenytoin respectively as reference standards. The most active compounds
      in scPTZ model were 1c, 2b, 5a and 7e showing 100% protection at 300 mg/kg upon
      intraperitoneal administration. Also, the effect of pre-treatment of three of the
      most active compounds (1c, 2b, 5a) on 4-amino pyridine-induced lethality in mice
      was investigated. Pre-treatment with these compounds significantly increased the
      latency for clonic and tonic seizures and prevented 4-amino pyridine induced
      death. Hence, this provides evidence for anticonvulsant activity of these
      compounds, and a neuroprotective activity for them. The structure-activity
      relationship was studied based on the obtained data.

PMID- 20823593
TI  - A new commercially viable synthetic route for donepezil hydrochloride: anti
      Alzheimer's drug.
AB  - An economical new process has been developed for the synthesis of donepezil
      hydrochloride (1) an anti-Alzheimer's drug. The process involves Darzen reaction
      of pyridine-4-carboxaldehyde and 2-bromo-5,6-dimethoxy indanone affording epoxide
      5,6-dimethoxy-3-(pyridine-4-yl)spiro[indene-2,2'-oxiran]-1(3H)-one (4) as a key
      intermediate. The one-pot deoxygenation of 4 and hydrogenation of the aryl moiety
      in high yield improved the overall yield of the process.

PMID- 20823594
TI  - A quadruped study on chitosan microspheres containing atorvastatin calcium:
      preparation, characterization, quantification and in-vivo application.
AB  - Atorvastatin is commonly used as a cholesterol lowering agent in patients.
      Recently, the neuroprotective effects of atorvastatin became the focus of many
      research studies. In this study, we have formulated chitosan microspheres
      containing atorvastatin calcium. In-vitro characterization of chitosan
      microspheres and quantification of atorvastatin calcium from formulations were
      also evaluated. The neuroprotective efficiency of atorvastatin calcium was
      investigated by an experimental spinal cord injury model. Atorvastatin calcium
      microspheres were implanted at the laminectomy area (1 mg/kg) immediately after
      trauma. Twenty-four hours after injury, motor functions of animals were scored
      according to modified Tarlov Scale. In spinal cord tissues tumor necrosis factor
      (TNF)-alpha, interleukin (IL)-1beta, IL-6 and lipid peroxidation levels were
      quantified and ultrastructural changes have been investigated. The results of all
      parameters indicate that microspheres containing atorvastatin calcium were
      capable of improving functional outcome, attenuating the expression of TNF-alpha,
      IL-1beta and IL-6; lowering lipid peroxidation levels and maintaining the
      preservation of the cellular uniformity.

PMID- 20823595
TI  - Design and development of oral mucoadhesive multiparticulate system containing
      atenolol: in vitro-in vivo characterization.
AB  - The aim of the present study was to prepare mucoadhesive multiparticulate system
      for oral drug delivery using ionic gelation technique. Microspheres of different
      mucoadhesive polymers including hydroxypropyl methylcellulose (HPMC) K15M and
      carbopol 971P were prepared. In this technique cross linking of sodium alginate
      with calcium chloride was done which retarded the release of drug from the
      mucoadhesive polymer. In the present work atenolol was used as model drug.
      Interaction studies performed using FT-IR spectroscopy revealed that there was no
      drug to polymer interactions. Multiparticulates so prepared were discrete, bulky,
      free flowing and showed an average encapsulation efficiency ranging from 23-74%.
      Particle size of the multiparticulates as determined by the scanning electron
      microscopic analysis (SEM) studies was found to be between 561-831 microm. The
      prepared formulations also exhibited a good mucoadhesive strength which was
      determined in in vitro conditions through falling film technique. The
      multiparticulate so prepared also exhibited a good swelling index which confirmed
      the strong mucoadhesive property of the formulation. Atenolol release from the
      multiparticulate system was regulated and extended until 12 h and exhibited a non
      Fickian anomalous transport from the swellable microspheres, as evident from the
      release rate exponent values which varied between 0.569-0.622. The stability
      studies performed on the optimized batch at 40 degrees C/75% RH for 90 d
      indicated no significant change in the physicochemical properties. In vivo
      radioimaging studies in rabbits showed the residence of mucoadhesive microspheres
      for 6-8 h in upper part of gastrointestinal tract (GIT).

PMID- 20823596
TI  - Cyathane diterpenoids and nitrogenous terphenyl derivative from the fruiting
      bodies of basidiomycete Phellodon niger.
AB  - Two new cyathane-type diterpenoids, nigernin A and B (1, 2), one new nitrogenous
      terphenyl derivative, phellodonin (3), together with three known compounds, 2',3'
      diacetoxy-3,4,5',6',4''-pentahydroxy-p-terphenyl, grifolin, and 4-O
      methylgrifolic acid, were isolated from the fruiting bodies of basidiomycete
      Phellodon niger. The structures of these new compounds were elucidated by
      spectroscopic methods and comparison with the data of known compounds in the
      literature. All these compounds were isolated from this fungus for the first
      time.

PMID- 20823597
TI  - Scandium-catalyzed propargylation of 1,3-diketones with propargyl alcohols
      bearing sulfur or selenium functional groups: useful transformation to furans and
      pyrans.
AB  - Propargylations of 1,3-diketones using 3-sulfanyl and 3-selanylpropargyl alcohols
      1 in MeNO(2)-H(2)O gave alkynyl ketones 2a-m, 2o-v and 6,7-dihydro-5H
      cyclohexa[b]pyran-5-ones 3k-n. With some bases, the useful propargylated 1,3
      diketones underwent intramolecular cyclization to give 6,7-dihydro-5H-benzofuran
      4-ones 4a-i or 4,5,6,7-tetrahydrobenzofurans 5p, 6p-v.

PMID- 20823598
TI  - A quantitative structure-activity relationship for the modulation effects of
      flavonoids on p-glycoprotein-mediated transport.
AB  - P-Glycoprotein accounts for multidrug resistance in chemotherapy patients and
      contributes to reduced oral bioavailability and distribution of drugs in the
      brain. The aim of this study was to establish the qualitative and quantitative
      structure-activity relationships (QSAR) of flavonoid modulation effects on P
      glycoprotein (P-gp)'s function. Using human colorectal adenocarcinoma (HCT15)
      cells as an in vitro model and fexofenadine as a P-gp substrate, the modulation
      effects on P-gp at three concentration levels of 22 representative compounds from
      four flavonoid families were evaluated. Results showed that the modulation
      (enhanced or inhibitory) effects could be divided into three ranges designated as
      enhanced (<100%) as compared to the control, low inhibitory (100-217%) and high
      inhibitory (>217%) as compared to verapamil. An optimal QSAR was constructed for
      Y1 (adjusted R(2)=0.4798), Y2 (adjusted R(2)=0.6809), and Y3 (adjusted
      R(2)=0.5902), respectively. This was further confirmed by a highly correlated
      plot of the predicted percent inhibition against observed values from a
      respective QSAR equation.

PMID- 20823599
TI  - Preparation of gel-core-solid lipid nanoparticle: a novel way to improve the
      encapsulation of protein and peptide.
AB  - Using thymopentin and insulin as the model protein-drugs, novel Gel-Core-solid
      lipid nanoparticle (SLN) with the hydrogel core and lipid shell were prepared by
      double emulsion and thermal sensitive gel technology, with the intention to
      improve the entrapment efficiency. Pluronic F127 and Glyceryl palmitostearate
      were selected as hydrogel material and lipid material, respectively. The particle
      sizes and zeta-potential were characterized by dynamic light scattering and
      electrophoretic light scattering. Transmission electron microscopy (TEM) was
      employed to investigate the structure of this Gel-Core-SLN. The Gel-Core-SLN was
      successfully prepared and the particle size was 305.2 nm with zeta potential of 
      17.15 mV. Observations by TEM confirmed that most solidified hydrogel particles
      were dispersed in the central of Gel-Core-SLN as a form of single core, which
      effectively prevented the diffusion of proteins to the external water phase
      during preparation process. The entrapment efficiency of thymopentin-loaded Gel
      Core-SLN and insulin-loaded Gel-Core-SLN were 61.97% and 57.36%, respectively.
      Both the two drug-loaded Gel-Core-SLNs showed relatively low burst release. The
      pharmacological availability of insulin-loaded Gel-Core-SLN was 6.02%. It was
      suggested that the Gel-Core-SLN could be a promising drug delivery system with
      the outstanding encapsulation efficiency, low burst release and relatively high
      pharmacological availability.

PMID- 20823600
TI  - Four new cembrane diterpenes isolated from an Okinawan soft coral Lobophytum
      crassum with inhibitory effects on nitric oxide production.
AB  - Four new cembrane diterpenes (1-4) and fifteen known cembranoids (5-19) were
      isolated from an Okinawan soft coral Lobophytum crassum. The structures of these
      four new cembranoids were determined on the basis of spectroscopic evidence. In
      particular, the absolute stereochemistry of 1, 2, 5 and 6 were elucidated by the
      application of the modified Mosher's method and circular dichroism (CD) spectral
      data. The inhibitory effects of some isolates were evaluated on nitric oxide (NO)
      production against a murine macrophage-like cell line (Raw 264.7). Cembranoids
      consisting of alpha-methylene-gamma-lactone, exhibited the significant effect on
      NO production.

PMID- 20823601
TI  - Synthesis of N-heteroaroyl aminosaccharide derivatives as fibroblast growth
      factor 2 signaling modulators.
AB  - Fibroblast growth factor 2 (FGF2) signaling plays an important role in
      angiogenesis. Heparin/heparan sulfate (HS) is required for FGF2 signaling but
      heparin mimics either promotes or inhibits FGF2 signaling. To take advantage such
      properties of heparin mimics, a series of N-heteroaroyl aminosaccharide
      derivatives were designed and synthesized as FGF2 signaling modulators. The
      bioactivity was determined in a FGF2 and heparin-dependent cell proliferation
      assay using FGFR1c expressing BaF3 cells. We found that most of the compounds
      inhibited heparin- and FGF2-dependent BaF3 cell proliferation while three
      compounds promoted the cell proliferation. These results suggest that the small
      molecular heparin mimics approach might be useful in developing novel anti
      angiogenic agents.

PMID- 20823602
TI  - Design, synthesis and evaluation of difunctionalized 4-hydroxybenzaldehyde
      derivatives as novel cholinesterase inhibitors.
AB  - A series of difunctionalized 4-hydroxybenzaldehyde derivatives were designed,
      synthesized and evaluated as cholinesterase (acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE)) inhibitors. The results demonstrated that all the
      compounds had more potent AChE and BChE inhibitory activities than galanthamine
      HBr, one of the best cholinesterase inhibitors known so far. The inhibition
      mechanism revealed that the best active compound 4e displayed a mix-type mode of
      AChE and BChE by its dual-site interactions with the catalytic triad active
      center and the peripheral anionic site (PAS) of enzyme. All these data suggested
      that further development of such compounds may be of interest.

PMID- 20823603
TI  - Butenolide and furandione from an endophytic Aspergillus terreus.
AB  - A new butenolide, aspernolide D (1), and furandione, asperterone (2), together
      with four known butenolides, butyrolactones I-IV and aspernolide B, were obtained
      from cultures of the endophytic fungus Aspergillus terreus, isolated from the
      flowering plant Mammea siamensis. The structures of these compounds were
      elucidated by analysis of NMR spectroscopic and mass spectrometric data.

PMID- 20823604
TI  - Two new drimane sesquiterpenoids from compound Changweikang and their inhibitory
      activity against nitric oxide production.
AB  - Two new drimane sesquiterpenoids, changweikangic acid A (1) and B (2), were
      isolated from Compound Changweikang. Their structures were established on basis
      of extensive spectroscopic analyses including two dimensional (2D) NMR and X-ray
      crystallographic data. The two compounds were evaluated for their inhibitory
      activity against nitric oxide production in lipopolysaccharide-activated
      macrophage cell line, RAW 264.7 cells.

PMID- 20823605
TI  - Three new stereoisomers of condensed tannins from the roots of Rosa multiflora.
AB  - Three new stereoisomers of condensed tannins (1-3), and four known phenolic
      compounds (4-7) were isolated from the 80% acetone extract of the roots of Rosa
      multiflora Thunberg. The structures of these compounds were elucidated using
      1D/2D NMR, high resolution (HR)-MS, and circular dichroism (CD) spectra. In order
      to evaluate their anti-oxidative and anti-inflammatory activities, their 1,1
      diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and inhibitory
      activity on nitric oxide (NO) production were determined.

PMID- 20823606
TI  - Two new glycosidic acids, quamoclinic acids G and H, of the resin glycosides
      (Convolvulin) from the seeds of Quamoclit pennata.
AB  - Two new glycosidic acids, quamoclinic acids G and H, were isolated from the
      glycosidic acid fraction afforded by alkaline hydrolysis of the ether-insoluble
      resin glycoside (convolvulin) fraction from the seeds of Quamoclit pennata BOJER.
      Both compounds are the first examples of bisdesmosides of glycosidic acid having
      the sugar linkages at C-3 of 3,11-dihydroxytetradecanoic acid (ipurolic acid) as
      well as at its C-11.

PMID- 20823607
TI  - Anticholinesterase and antioxidant constituents from Gloiopeltis furcata.
AB  - Activity-directed isolation of the ethyl acetate, methylene chloride and n-hexane
      fractions of Gloiopeltis furcata resulted in the isolation of 18 compounds. Their
      structures were elucidated as 2-(3-hydroxy-5-oxotetrahydrofuran-3-yl)acetic acid
      (1), glutaric acid (2), succinic acid (3), nicotinic acid (4), (E)-4-hydroxyhex-2
      enoic acid (5), cholesterol (6), 7-hydroxycholesterol (7), uridine (8), glycerol
      (9), 5-(hydroxymethyl)-2-methoxybenzene-1,3-diol (10), (5E,7E)-9-oxodeca-5,7
      dienoic acid (11), (Z)-3-ethylidene-4-methylpyrrolidine-2,5-dione (12),
      dehydrovomifoliol (13), loliolide (14), cholesteryl stearate (15), palmitic acid
      (16), cis-5,8,11,14,17-eicosapentaenoic acid (17) and alpha-linolenic acid (18)
      on the basis of spectroscopic and chemical evidences. Their anticholinesterase
      and antioxidant activities were evaluated via inhibitory activities on
      acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) as well as
      scavenging activities on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and
      peroxynitrite (ONOO(-)). All isolated compounds (1-18) exhibited moderate AChE
      inhibitory activities with IC(50) values ranging from 1.14-12.50 microg/ml,
      whereas 1, 7, 9, 17, and 18 showed mild BChE inhibitory activities with IC(50)
      values ranging from 5.57-15.89 microg/ml. Although most of the compounds isolated
      were lacking the scavenging activity on DPPH radical and ONOO(-), 5 and 10 showed
      good DPPH radical scavenging activity, and 5, 10, and 16 showed potent ONOO(-)
      scavenging activity.

PMID- 20823608
TI  - New 3beta,5alpha,6beta-trihydroxysteroids from the octocorals Bebryce sp.
      (Plexauridae) and Carijoa sp. (Clavulariidae).
AB  - A new 3beta,5alpha,6beta-trihydroxysteroid, bebryceoid A (1), has been isolated
      from an octocoral Bebryce sp. In addition, an octocoral Carijoa sp. yielded two
      new 3beta,5alpha,6beta-trihydroxysteroids, carijoids A (2) and B (3). The
      structures of steroids 1-3 were elucidated by spectroscopic methods and by
      comparison of the spectral data with those of known steroid analogues.

PMID- 20823609
TI  - Solid-state carbon NMR characterization and investigation of intrinsic
      dissolution behavior of fluconazole polymorphs, anhydrate forms I and II.
AB  - Solid-state (13)C nuclear magnetic resonance ((13)C-SSNMR) revealed significant
      differences in the chemical shift of specific carbon atoms between two
      fluconazole polymorphs, reflecting a change in molecular conformation. A single
      resonance signal without splitting was observed in the spectrum of anhydrate form
      II, while the spectrum of anhydrate form I showed signals with splitting,
      indicating the presence of two dissimilar molecular conformations in the unit
      cell of anhydrate form I. The Fourier transform infrared (FT-IR) and Raman
      spectra associated with the triazole group, the 2,4-difluorobenzyl group, and the
      propane backbone provided also evidence of structural differences between forms I
      and II accompanying with (13)C-SSNMR. (1)H T(1) relaxation times, measured using
      saturation recovery experiments, showed that the metastable anhydrate form II was
      more mobile than the stable form I. The solubility and intrinsic dissolution
      tests showed that the anhydrate form II was more soluble and dissolved faster
      than the anhydrate form I.

PMID- 20823610
TI  - Triterpenoid saponins from Ardisia gigantifolia.
AB  - Four new triterpenoid saponins (1-4) were isolated from the rhizome of Ardisia
      gigantifolia STAPF. The structures of new saponins were established as 3beta-o
      alpha-L-rhamnopyranosyl-(1-->3)-[beta-D-xylopyranosyl-(1-->2)]-beta-D
      glucopyranosyl-(1-->4)-[beta-D-glucopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl
      16alpha-hydroxy-13,28-epoxy-oleanane (1), 3beta-o-alpha-L-rhamnopyranosyl-(1-->3)
      [beta-D-xylopyranosyl-(1-->2)]-beta-D-glucopyranosyl-(1-->4)-[beta-D-glucopyrano
      syl-(1-->2)]-alpha-L-arabinopyranosyl-16alpha-hydroxy-13,28-epoxy-30-acetoxy
      oleanane (2), 3beta-o-alpha-L-rhamnopyranosyl-(1-->3)-[beta-D-glucopyranosyl-(1-
      >4)-beta-D-xylopyranosyl-(1-->2)]-beta-D-glucopyranosyl-(1-->4)-[beta-D
      glucopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl-16alpha-hydroxy-13,28-epoxy
      oleanane (3) and 3beta-o-alpha-L-rhamnopyranosyl-(1-->3)-[beta-D-xylopyranosyl-(1
      ->2)]-beta-D-glucopyranosyl-(1-->4)-[beta-D-6-O-acetylglucopranosyl-(1-->2)]
      alpha-L-arabinopyranosyl-16alpha-hydroxy-13,28-epoxy-oleanane (4) were isolated
      from Ardisia gigantifolia STAPF. Their structures were elucidated by means of
      (1)H- and (13)C-NMR spectroscopic studies, including 2D-NMR technique. The
      cytotoxic activities of saponins 1-4 are reported against three human cancer cell
      lines, namely, Hela human cervical carcinoma cells, EJ human bladder tumor cells,
      and BCG-823 human gastric carcinoma cells.

PMID- 20823611
TI  - Enantioselective synthesis of the novel chiral sulfoxide derivative as a glycogen
      synthase kinase 3beta inhibitor.
AB  - Glycogen synthase kinase 3beta (GSK-3beta) inhibitors are expected to be
      attractive therapeutic agents for the treatment of Alzheimer's disease (AD).
      Recently we discovered sulfoxides (S)-1 as a novel GSK-3beta inhibitor having in
      vivo efficacy. We investigated practical asymmetric preparation methods for the
      scale-up synthesis of (S)-1. The highly enantioselective synthesis of (S)-1 (94%
      ee) was achieved by titanium-mediated oxidation with D-(-)-diethyl tartrate on
      gram scale.

PMID- 20823612
TI  - Site-selective cross-coupling of dichlorinated benzo-fused nitrogen-heterocycles
      with Grignard reagents.
AB  - Site-selective cross-coupling of dihaloarenes constitutes a useful method for
      synthesis of multi-substituted arenes. In this paper, we report the site
      selective cross-coupling of dichlorinated benzo-fused nitrogen-heterocycles
      having two chloro groups on the benzene ring. These dichlorinated heterocycles
      reacted with Grignard reagents in the presence of PdCl(2)(PCy(3))(2) at the
      positions ortho to the nitrogen-based substituents with high selectivities. A
      mechanism in which interaction between Lewis acidic Mg and Cl of the ortho
      position facilitates C-Cl bond cleavage is proposed.

PMID- 20823613
TI  - Six new acylated anthocyanins from red radish (Raphanus sativus).
AB  - Six new acylated anthocyanins (1-6) were isolated along with the three known
      congeners (7-9) from the fresh roots of red radishes (Raphanus sativus L.)
      cultivated by our group. Their chemical structures were elucidated by
      spectroscopic properties. Among the six new anthocyanins, the five constituents
      (1, 2, 4-6) were shown to contain the malonyl function at 6-OH in the
      glucopyranosyl residue linked to C-5 in the pelargonidin nucleus.

PMID- 20823614
TI  - Four new sesquiterpenoids from the roots of Incarvillea arguta and their
      inhibitory activities against lipopolysaccharide-induced nitric oxide production.
AB  - Four new sesquiterpenoids, argutosines A-D (1-4), together with two known ones
      (5, 6), were isolated from the roots of Incarvillea arguta. Their chemical
      structures were elucidated on the basis of MS, NMR spectroscopic analysis. All
      the sesquiterpenoids were tested for inhibitory activities against
      lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7
      macrophages. Argutosines A, B and C (1-3) showed potent inhibitory activities
      with IC(50) values of 2.05, 0.55, and 9.87 microM, respectively.

PMID- 20823615
TI  - Scutebarbatines W-Z, new neo-clerodane diterpenoids from Scutellaria barbata and
      structure revision of a series of 13-spiro neo-clerodanes.
AB  - Four new neo-clerodane diterpenoids, scutebarbatines W-Z (1-4), were isolated
      from the ethanol extract of Scutellaria barbata (Labiatae), and their structures
      were elucidated on the basis of extensive spectroscopic studies. In addition, the
      proposed structures of at least seven 13-spiro subtype neo-clerodanes:
      scutehenanine B (5), scutebarbatine G (6), 6-O-nicotinoylscutebarbatine G (7),
      barbatin A (8), 6,7-di-O-nicotinoylscutebarbatine G (9), 6-O-nicotinoyl-7-O
      acetylscutebarbatine G (10), and scutebarbatine F (11), reported by Dai and co
      workers from the same species, were incorrectly assigned and have been revised by
      reanalysis of the published NMR data.

PMID- 20823616
TI  - Nitrosation of N-methyl derivatives of uric acid and their transnitrosation
      ability to N-acetylcysteine.
AB  - When 1,3-dimethyluric acid was treated with a nitric oxide donor, diethylamine
      NONOate, in an aerobic neutral solution and the reaction was analyzed by HPLC,
      1,3-dimethyluric acid was consumed to yield a nitrosated derivative, which
      decomposed with a half-life of 17.9 min at pH 7.4 and 37 degrees C. When 1,3,7
      trimethyluric acid was treated with diethylamine NONOate, no consumption of 1,3,7
      trimethyluric acid was observed. However, in the reaction of N-acetylcysteine
      with diethylamine NONOate, the yield of N-acetyl-S-nitrosocysteine increased by
      the addition of 1,3,7-trimethyluric acid as well as 1,3-dimethyluric acid. For
      1,3,7,9-tetramethyluric acid, no consumption in the reaction with diethylamine
      NONOate and no effect on the S-nitrosation were observed. These results suggest
      that 1,3-dimethyluric and 1,3,7-trimethyluric acids are both nitrosated by
      diethylamine NONOate on the nitrogen atom of their oxoimidazole ring, although
      the half-life of the nitrosated 1,3,7-trimethyluric acid is too short to detect
      by HPLC. Consequently, these two acids can act as vehicles of nitric oxide.

PMID- 20823617
TI  - Inhibitory effects of acylated acyclic sesquiterpene oligoglycosides from the
      pericarps of Sapindus rarak on tumor necrosis factor-alpha-induced cytotoxicity.
AB  - Four new acylated acyclic sesquiterpene oligoglycosides (1-4) were isolated from
      the pericarps of Sapindus rarak DC. together with four known acyclic
      sesquiterpene oligoglycosides, mukuroziosides Ia (5), Ib (6), IIa (7), and IIb
      (8). Their structures were elucidated on the basis of chemical and
      physicochemical evidence. These newly isolated compounds (1-4) were found to show
      inhibitory effects on tumor necrosis factor-alpha-induced cytotoxicity in L929
      cells at concentrations of 30-100 microM.

PMID- 20823619
TI  - Dentin bond durability and water sorption/solubility of one-step self-etch
      adhesives.
AB  - The purpose of this study was to evaluate the dentin bonding durability of three
      HEMA-containing one-step self-etch adhesives after one-year water storage and to
      measure the amounts of their water sorption/solubility. OptiBond All-In-One (OP),
      Bond Force (BF) and Clearfil S3Bond (S3) were applied to the dentin surfaces
      according to manufacturers' instructions. Bond strengths to dentin were
      determined using uTBS test after water storage for 24 hours, six months, and one
      year. In addition, water sorption and solubility of the polymerized adhesives
      were measured. The uTBS of S3 and OP significantly decreased after one year. On
      the other hand, for BF there were no significant differences in uTBS between all
      storage periods. There were significant differences in water sorption and
      solubility among the adhesives (BF>S3>OP). The initial amounts of water sorption
      and solubility of the three adhesives did not affect their bonding durability to
      dentin.

PMID- 20823620
TI  - Morphological and chemical analysis of different precipitates on mineral trioxide
      aggregate immersed in different fluids.
AB  - The purpose of this study was to analyze the ultrastructures and chemical
      compositions of precipitates formed on mineral trioxide aggregate (MTA; White
      ProRoot MTA) immersed in distilled water (DW) or phosphate buffered saline (PBS),
      based on the attribution that MTA's bioactivity and sealing ability are
      influenced by its interaction with the external fluid environment. After 1 and 14
      days of immersion, precipitates formed on MTA disks were analyzed using
      wavelength-dispersive X-ray spectroscopy electron probe microanalyzer with image
      observation function (SEM-EPMA; EPMA1601, Shimadzu, Kyoto, Japan), and Fourier
      transform-infrared (FT-IR) spectroscopy. On DW specimens, cubic-like crystals
      containing Ca, O, and C (17, 66, and 17 at% respectively) were produced. State
      analysis of calcium k(beta)spectrum also revealed calcium hydroxide. On PBS
      specimens, acicular-spherical and lath-like crystals with Ca/P molar ratios of
      1.42 and 1.58 respectively were produced. In conclusion, the precipitates formed
      on DW specimens were identified as calcium carbonate and calcium hydroxide
      primarily, whereas the precipitates on PBS specimens were inferred to be
      amorphous calcium phosphate.

PMID- 20823621
TI  - Thin resin coating by dual-application of all-in-one adhesives improves dentin
      bond strength of resin cements for indirect restorations.
AB  - This study was evaluated the tensile bond strength (TBS) of resin cements to
      bovine dentin resin-coated with all-in-one adhesive systems. Each of the dual
      polymerizing resin cements; Link Max, Clearfil Esthetic Cement, Bistite II and
      Chemiace II were used to bond indirect resin disks to bovine dentin, as control,
      or coated by single-application or by dual-application of an adhesive system from
      the same manufacturer; G-Bond, Clearfil Tri-S Bond, Tokuyama Bond Force and
      Hybrid-Coat (n=10). After 24-hour water storage, TBSs were measured. The fracture
      pattern and the adhesive interface were observed using an SEM. Dual-application
      of the adhesive yielded significantly higher TBSs compared to control and single
      application groups for all materials (p<0.001). From the limited information of
      this study, it was concluded that dual-application of all-in-one adhesive systems
      created a thin coating on dentin, and significantly improved the bond strengths
      of resin cements.

PMID- 20823622
TI  - Study of corrosion of combinations of titanium/Ti-6Al-4V implants and dental
      alloys.
AB  - Metal ions released in 1% lactic acid solution from combinations of titanium
      fixtures with superstructures made of dental precious metal alloys (dental
      alloys) and titanium and differences based on the fixing method were
      investigated. In combinations of titanium with dental alloys, the level of Ti
      release was influenced by micro-structure of titanium: it was lower when the
      grain size was smaller. In titanium-titanium combinations, differences in the
      micro-structure of metal also markedly influenced the dissolution: the level of
      release increased when the micro-structure of titanium was different. The Ti and
      V release levels were higher in combination with titanium alloy and titanium than
      with titanium alloy and dental alloys. Regarding the superstructure-fixture
      fixing method, the level of Ti release was significantly lower in cement than in
      direct fixation.

PMID- 20823624
TI  - Homeostatic inflammation, an emerging concept.

PMID- 20823623
TI  - Minimally invasive surgery for primary hyperparathyroidism with or without
      intraoperative parathyroid hormone monitoring.
AB  - We analyzed the utility of intraoperative parathyroid hormone (IOPTH) monitoring
      in minimally invasive surgery for primary hyperparathyroidism (pHPT). The
      subjects were the 167 consecutive patients with pHPT performed initial operation
      with or without IOPTH between January 2000 and December 2006. Patients were
      divided into 2 groups. A group who underwent surgery without IOPTH monitoring
      (Group 1; n=87), and a group who underwent surgery with IOPTH monitoring (Group
      2; n=80), in which IOPTH was measured at 5, 10, 15 minutes after excision of the
      abnormal parathyroid gland. Criterion for evaluation as a cure was a drop in
      intact PTH level of 50% or more from the preoperative baseline value. The overall
      cure rate in Group 1 was 93.1%. An enlarged parathyroid gland that was consistent
      with the results of a preoperative imaging study was found in 84 patients
      (96.6%). The overall cure rate in Group 2 was 97.5%. In 7 of the patients, there
      was no drop of 50% or more at any of the 3 points in time measured. Two of these
      patients were found to have had double adenomas, one on each side, during the
      initial surgery. Three others were eucalcemic and had normal intact PTH values
      after surgery, and the remaining 2 patients had persistent disease. Although
      preoperative localization studies are accurate and essential, IOPTH monitoring
      improves the cure rate of minimally invasive parathyroidectomy. IOPTH monitoring
      is a valuable adjunct to achieve adequate intraoperative decision-making,
      recognizing and resecting additional image-negative hyperfunctioning lesions.

PMID- 20823625
TI  - Occupational exposure in methyl bromide manufacturing workers: 17-year follow-up
      study of urinary bromide ion concentration for biological monitoring.
AB  - To elucidate the circumstances of their occupational exposure to methyl bromide
      (MeBr), we conducted a 17-yr study on 124 workers employed by a MeBr
      manufacturer. Subjects were classified into three groups according to the nature
      of their work: synthesis group, filling group, and other group. Urinary
      concentrations of bromide ion (Br(-)) were assessed, and data attained via MeBr
      health examinations were analyzed. The highest Br(-) concentrations were seen in
      the synthesis group, with a median value of 13.0 MUg/mg CRE (2.5-51.8), followed
      by the filling group, with a concentration of 11.9 MUg/mg CRE (3.1-34.8). Both
      values were significantly higher than the levels noted in the other group
      (p<0.001). Three major opportunities for exposure were identified: during
      exchange of reaction equipment for maintenance or cleaning, during operations to
      adjust for weight variations after filling canisters, or when canisters were
      recycled. Overall, however, the workplace environment concentration remained
      largely below the administrative control level throughout the study period.
      Therefore, while this was a relatively well-controlled workplace, exposure
      opportunities still arose when performing certain tasks, indicating the need for
      ongoing improvement in workplace procedures and underscoring the importance of
      biological monitoring.

PMID- 20823626
TI  - Monitoring of occupational exposure to volatile organohalogen solvents (VOXs) in
      human urine samples of dry-cleaner workers by TLHS-DAI-GC-ECD procedure.
AB  - Chlorinated hydrocarbon solvents are often used for dry-cleaning clothes in the
      laundry industry. The object of this study was to monitor the occupational
      exposure of dry-clean employees coming into contact with VOXs. Twenty five
      workers collected their urine samples before the work shift, after 4 h of work
      and after the work shift. The analyses of urine samples and solvents used in dry
      cleaning were performed using TLHS-DAI-GC-ECD. Chloroform was detected in all
      urine samples, and dichloromethane and tetrachloroethene in nearly all urine
      samples collected before and after the work shift. The concentrations of the
      compounds determined in urine samples were higher at the end of the workday in
      directly exposed individuals. Concentrations of the compounds determined in urine
      samples depended mainly on the type of activities carried out at the dry-cleaning
      establishments.

PMID- 20823627
TI  - Pericardial plaque: a unique complication of silicosis.
AB  - The heart and the respiratory system are closely connected in such a way that
      disorders of one system would influence the function of the other. This unique
      case of silicosis complicated by corpulmonale associated with pericardial plaque
      formation in a young adult male is reported here due to an unknown complication
      of silicosis.

PMID- 20823628
TI  - Job satisfaction, common cold, and sickness absence among white-collar employees:
      a cross-sectional survey.
AB  - The purpose of this study is to examine the independent association of job
      satisfaction with common cold and sickness absence among Japanese workers. A
      total of 307 apparently healthy white-collar employees (165 men and 142 women),
      aged 22-69 (mean 36) yr, completed a questionnaire survey during April to June,
      2002. Global job satisfaction was measured by a 4-item scale from the Japanese
      version of a generic job stress questionnaire with higher scores indicating
      greater satisfaction. Information about whether the employees had a common cold
      (within the past 6 months) and sickness absence (within the past 12 months) was
      self-reported. Hierarchical log-linear Poisson regression analysis controlling
      for confounders revealed that greater job satisfaction was inversely correlated
      with days (B = -0.116; p<0.001) and times (B = -0.058; p = 0.067) of common cold
      and days (B = -0.160; p<0.001) and times (B = -0.141; p<0.001) of sickness
      absence. Our findings suggested that poor job satisfaction is associated with
      both common cold and sickness absence.

PMID- 20823629
TI  - Thermal environment assessment reliability using temperature--humidity indices.
AB  - A reliable assessment of the thermal environment should take into account the
      whole of the six parameters affecting the thermal sensation (air temperature, air
      velocity, humidity, mean radiant temperature, metabolic rate and thermo-physical
      properties of clothing). Anyway, the need of a quick evaluation based on few
      measurements and calculations has leaded to like best temperature-humidity
      indices instead of rational methods based on the heat balance on the human body.
      Among these, Canadian Humidex, preliminarily used only for weather forecasts, is
      becoming more and more widespread for a generalized assessment of both outdoor
      and indoor thermal environments. This custom arouses great controversies since
      using an index validated in outdoor conditions does not assure its indoor
      reliability. Moreover is it really possible to carry out the thermal environment
      assessment ignoring some of variables involved in the physiological response of
      the human body? Aiming to give a clear answer to these questions, this paper
      deals with a comparison between the assessment carried out according to the
      rational methods suggested by International Standards in force and the Humidex
      index. This combined analysis under hot stress situations (indoor and outdoor)
      has been preliminarily carried out; in a second phase the study deals with the
      indoor comfort prediction. Obtained results show that Humidex index very often
      leads to the underestimation of the workplace dangerousness and a poor
      reliability of comfort prediction when it is used in indoor situations.

PMID- 20823630
TI  - Respiratory morbidity induced by occupational inhalation exposure to
      formaldehyde.
AB  - The potential of formaldehyde to produce chronic respiratory tract disease
      remains a controversial issue. The main purpose of this study was to investigate
      the respiratory effects, if any, of long term occupational exposure to
      formaldehyde. This cross-sectional study was carried out at a local melamine
      formaldehyde resin producing plant. The study population consisted of seventy
      exposed and 24 non-exposed (referent) employees. Using respiratory questionnaire,
      data on respiratory symptoms were gathered. Atmospheric concentrations of
      formaldehyde were measured at different contaminated areas of the plant.
      Similarly, the parameters of pulmonary function were measured at the beginning
      (preshift) and at the end (postshift) of the first working day of the week. The
      results showed that airborne concentrations of formaldehyde exceeded current
      permissible levels. Additionally, significant decrements in some preshift and
      postshift parameters of pulmonary function of exposed workers were noted.
      However, a relative recovery in lung functional capacity observed following
      temporary cessation of exposure (preshift values). Furthermore, exposed workers
      had higher prevalence rates of regular cough, wheezing, phlegm, shortness of
      breath, chest tightness and episodes of chest illness associated with cold. The
      findings of this study collectively indicate that exposure to formaldehyde may
      induce respiratory symptoms, acute partially reversible and chronic irreversible
      functional impairments of the lungs.

PMID- 20823631
TI  - Exploring risk groups workplace bullying with categorical data.
AB  - In this study, we first explore whether different exposure groups of workplace
      bullying exist, employing a large, heterogeneous sample. The results show six
      different exposure groups: almost 30.5% is not bullied since they report hardly
      any negative act at work at all, 27.2% face some limited work criticism, 20.8%
      face limited negative encounters, 8.3% is occasionally bullied, 9.5% are
      predominately work related bullied, and a total of 3.6% can be seen victims of
      severe workplace bullying. In a second step, the relationship between the
      identified target groups and social demographics were investigated using
      multinomial logistic regression to identify risk groups of workplace bullying.
      Employees between the age of 35 and 54, public servants, blue-collar workers, as
      well as employees working in the food and manufacturing industries have a
      significantly elevated risk to be victims of workplace bullying. In contrast,
      employees younger than 25, employees with a temporary contract, teachers, nurses
      and assistant nurses are those least likely at risk. These findings are important
      for policymakers at the national and organisational level as they assist in
      focussing towards possible avenues to prevent workplace bullying.

PMID- 20823632
TI  - Personal exposure to metal fume, NO2, and O3 among production welders and non
      welders.
AB  - The objective of this study was to characterize personal exposures to welding
      related metals and gases for production welders and non-welders in a large
      manufacturing facility. Welding fume metals and irritant gases nitrogen dioxide
      (NO(2)) and ozone (O(3)) were sampled for thirty-eight workers. Personal exposure
      air samples for welding fume metals were collected on 37 mm open face cassettes
      and nitrogen dioxide and ozone exposure samples were collected with diffusive
      passive samplers. Samples were analyzed for metals using Inductively Coupled
      Plasma Mass Spectrometry (ICP-MS) and welding fume metal exposure concentrations
      were defined as the sum of welding-related metals mass per volume of air sampled.
      Welding fume metal exposures were highly variable among similar types of welding
      while NO(2) and O(3) exposure were less variable. Welding fume metal exposures
      were significantly higher 474 MUg/m(3) for welders than non-welders 60 MUg/m(3)
      (p=0.001). Welders were exposed to higher concentrations of NO(2) and O(3) than
      non-welders but the differences were not statistically significant. Welding fume
      metal exposure concentrations for welders performing gas metal arc welding (GMAW)
      and shielded metal arc welding (SMAW) were higher than welders performing gas
      tungsten arc welding (GTAW). Non-welders experienced exposures similar to GTAW
      welders despite a curtain wall barrier separating welding and non-welding work
      areas.

PMID- 20823633
TI  - A study on industrial accident rate forecasting and program development of
      estimated zero accident time in Korea.
AB  - To begin a zero accident campaign for industry, the first thing is to estimate
      the industrial accident rate and the zero accident time systematically. This
      paper considers the social and technical change of the business environment after
      beginning the zero accident campaign through quantitative time series analysis
      methods. These methods include sum of squared errors (SSE), regression analysis
      method (RAM), exponential smoothing method (ESM), double exponential smoothing
      method (DESM), auto-regressive integrated moving average (ARIMA) model, and the
      proposed analytic function method (AFM). The program is developed to estimate the
      accident rate, zero accident time and achievement probability of an efficient
      industrial environment. In this paper, MFC (Microsoft Foundation Class) software
      of Visual Studio 2008 was used to develop a zero accident program. The results of
      this paper will provide major information for industrial accident prevention and
      be an important part of stimulating the zero accident campaign within all
      industrial environments.

PMID- 20823634
TI  - Safety evaluation of rock wool after nasal inhalation in rats.
AB  - Asbestos is reported to cause pulmonary fibrosis, and its use has been banned. We
      examined the biopersistence and histopathological effect of rock wool (RW) fibers
      in rat lungs by a nose-only inhalation exposure study. Twenty-four rats were
      exposed to RW fibers for 6 h daily for 5 consecutive days. Six rats each were
      sacrificed shortly and 1, 2, and 4 wk after exposure, and the fiber numbers and
      sizes in lungs were determined. The fiber number in the lungs 4 wk after exposure
      significantly decreased. The clearance half time was 28 d for fibers with L>20
      MUm and 50 d for World Health Organization fibers. The reasons for the decrease
      in number and size of fibers include: 1) discharge outside of the body by
      mucociliary movement, 2) dissolution by body fluid, and 3) phagocytosis and
      digestion by alveolar macrophages. Twelve rats were used for histopathological
      examination, and the pathological changes were classified by Wagner's criteria.
      As a result, changes up to only Grade 2 were observed. The reason for the
      increase in macrophage number was considered to be a transient reaction of body
      defense. These results suggest that RW has low biopersistence and only a limited
      pathological effect.

PMID- 20823635
TI  - Skin lead contamination of family members of boat-caulkers in southern Thailand.
AB  - Powdered lead oxide (Pb(3)O(4)) is used in the wooden-boat repair industry as a
      constituent of the caulking material. This study compared skin lead of household
      members of caulkers' and control homes, and examined the relationship of
      household member's skin lead with household floor lead loading (FLL) and dust
      lead content (DLC). FLL and DLC were measured in 67 caulkers' houses and 46
      nearby houses with no known lead exposure. In each household, wipe specimens of
      skin lead were obtained from one selected family member. Hand lead loading (HdLL)
      and foot lead loading (FtLL) were significantly higher in family members of
      caulkers than controls (geometric mean 64.4 vs. 36.2 MUg m(-2); p = 0.002 and
      77.8 vs 43.8 MUg m(-2); p = 0.002, respectively). This pattern mirrored FLL and
      DLC, which were also higher in caulkers' than in control houses (geometric mean
      109.9 vs. 40.1 MUg m(-2); p<0.001 and 434.8 vs 80.8 MUg g(-1); p<0.001,
      respectively). Multiple linear regression modelling revealed FLL to be a better
      predictor than DLC for HdLL in all age groups and for FtLL in adult family
      members. In conclusion, skin lead levels are elevated in family members living in
      a lead-exposed worker's house and are related to the levels of household lead
      contamination.

PMID- 20823636
TI  - Effects of load carrying methods and stair slopes on physiological response and
      postures during stairs ascending and descending.
AB  - The purpose of this study was to examine the effects of load carrying methods,
      stair slopes and walking speeds on heart rate and walking postures. Nine
      participants climbed up and down stairs with various stair slopes (24 degrees ,
      30 degrees  and 36 degrees ), walking speeds (72, 96, and 132 steps per minute),
      and using different load carrying methods (empty loads, backpack, and hand-held).
      The effects of these factors on heart rate, Borg-RPE and flexion angles of knee
      joints, hip joints and trunk angles were investigated. This study demonstrated
      that increased stair slopes and walking speed were associated with increased
      heart rate and RPE. The heart rate for empty loads subjects was lowest, followed
      by backpack load and hand-held load. Climbing stairs with larger inclination was
      associated with smaller knee joint flexion angle and larger trunk and hip joint
      flexion angle. In conclusion, it is easier for subjects to carry a load of the
      same weight up stairs by backpack than by hand. However, the stair slope should
      be less than 30 degrees . Thus, the standard fixed stair slope (30 degrees  of
      stair slope) on recommended for riser height and tread depth are 160 mm (6.5
      inches) and tread depth 280 mm (11 inches).

PMID- 20823637
TI  - Use of a holder-vacuum tube device to save on-site hands in preparing urine
      samples for head-space gas-chromatography, and its application to determine the
      time allowance for sample sealing.
AB  - To facilitate urine sample preparation prior to head-space gas-chromatographic
      (HS-GC) analysis. Urine samples containing one of the five solvents (acetone,
      methanol, methyl ethyl ketone, methyl isobutyl ketone and toluene) at the levels
      of biological exposure limits were aspirated into a vacuum tube via holder, a
      device commercially available for venous blood collection (the vacuum tube
      method). The urine sample, 5 ml, was quantitatively transferred to a 20-ml head
      space vial prior to HS-GC analysis. The loaded tubes were stored at +4 C in dark
      for up to 3 d. The vacuum tube method facilitated on-site procedures of urine
      sample preparation for HS-GC with no significant loss of solvents in the sample
      and no need of skilled hands, whereas on-site sample preparation time was
      significantly reduced. Furthermore, no loss of solvents was detected during the 3
      d storage, irrespective of hydrophilic (acetone) or lipophilic solvent (toluene).
      In a pilot application, high performance of the vacuum tube method in sealing a
      sample in an air-tight space succeeded to confirm that no solvent will be lost
      when sealing is completed within 5 min after urine voiding, and that the
      allowance time is as long as 30 min in case of toluene in urine. The use of the
      holder-vacuum tube device not only saves hands for transfer of the sample to air
      tight space, but facilitates sample storage prior to HS-GC analysis.

PMID- 20823638
TI  - An integrated model for the assessment of stress-related risk factors in health
      care professionals.
AB  - To assess the risk from exposure to occupational stress and burnout in health
      care workers (HCW), a cross-sectional study was planned to compare objective data
      that can represent potential job stressors in hospital wards and subjective
      symptoms reported by the workers. Medical doctors, nurses and ancillary workers
      of the Internal Medicine Wards of a large public hospital in Northern Italy
      participated in the study. Three subjective questionnaires were administered: the
      Job Content Questionnaire (JCQ), the State-Trait Anxiety Inventory (STAI), the
      Maslach Burnout Inventory (MBI). In addition, seven objective parameters were
      collected as average during the 3 months period prior to the study: a) working
      understaffed; b) ratio number of patients/HCW on service; c) ratio number of HCW
      on sick leave/ HCW on service; d) number of skipped days off after night shifts;
      e) days of sick leave; f) number of deceased patients; g) number of accidents at
      work. A total group of 230 HCW were examined, employed in six different sub-units
      of the Medical wards. The female workers were 67.8% and the male workers 32.2%,
      the mean age was 37.4 yr (SD 9.3) in the total group of HCW, 35.1 yr (SD 7.9) in
      females and 42.3 yr (SD 10.3) in males. The average scores of subjective and
      objective parameters resulted significantly higher in the same sub-units. The
      correlation analysis showed that the subjective questionnaires were highly inter
      related. The multivariate analysis showed that the days of sick leave were
      significantly related to the subjective questionnaires, and the subjective
      subscales of emotional exhaustion (from MBI), job demand and decision latitude
      (from JCQ) and STAIt were significantly related to some of the objective
      parameters. These results support the integrated use of multiple subjective and
      objective assessment as the most appropriate approach for the evaluation of
      occupational stress.

PMID- 20823639
TI  - Changes in oxidative stress biomarker and gene expression levels in workers
      exposed to volatile organic compounds.
AB  - Exposure to volatile organic compounds (VOCs) was known to result in immunologic,
      respiratory, carcinogenic, reproductive, neurologic, and cardiovascular effects.
      However, the mechanisms by which VOCs induce these adverse health effects are not
      well understood. To evaluate the change of oxidative stress biomarker and gene
      expression levels in workers exposed to VOCs, we obtained urine and blood samples
      from 21 subjects before and after occupational exposure to VOCs. We measured
      levels of muconic acid (MuA), hippuric acid (HA), mandelic acid (MaA), and methyl
      hippuric acid (MHA) as urinary exposure biomarkers for benzene, toluene,
      ethylbenzene, and xylene (collectively BTEX), and malondialdehyde (MDA) and 8
      hydroxydeoxyguanine (8-OHdG) as oxidative stress biomarkers in all subjects. We
      also evaluated BTEX-mediated RNA expression using cDNA microarray in 14 subjects.
      HA and MHA levels were higher following occupational exposure to VOCs (p < 0.01).
      In the linear regression analysis, HA ratios of after- and before-exposure were
      found to be significantly associated with increase of MDA ratios of after- and
      before-exposure after controlling for age, body mass index, and smoking (beta =
      0.06, p = 0.031). Evaluation of the gene expressions by HA showed that 23 gene
      expressions were found to be significantly associated with HA levels after
      adjusting for age, body mass index, and smoking (p < 0.001). In particular,
      expressions of ENO3 and CDNA FLJ39461 fis among the 23 genes were significantly
      associated with the change in MDA level (p < 0.05). Our study results suggest
      that exposure to VOCs, specifically toluene, induces oxidative stress and various
      gene expression change of which some may be responsible for oxidative stress.

PMID- 20823640
TI  - Work-related cerebrovascular and cardiovascular diseases (WR-CVDs) in Korea.
AB  - The effects of work on the heart are mediated by chemical, physical, and
      psychological stressors. It is standard clinical practice to assess personal risk
      factors such as cigarette smoking, hypertension, and cholesterol. Evaluation of a
      patient's acute symptoms and activity level at the time of presentation is also
      standard practice. However, clinicians typically do not assess workplace risk
      factors; nor do they usually identify the location and its possible exposures
      that may have contributed to the patient's symptoms. In Korea, work-related
      cerebrovascular and cardiovascular diseases (WR-CVDs) are among the most
      compensated cases, second only to work-related musculoskeletal disorders (WR
      MSDs). The average accumulated insurance benefit per injured worker is an
      estimated USD 75,000, which is thought to have a major impact on the financial
      stability of insurers. Therefore, the present study was performed to 1) review
      the physicochemical agents of cardiovascular diseases in Korea, 2) review the
      effects of psychosocial factors such as work-related stress on WR-CVDs in Korea,
      and 3) discuss the concepts and perspectives of WR-CVDs in Korea by comparing
      with those in Japan.

PMID- 20823641
TI  - The new concept of therapeutic strategy for neuroendocrine tumors: important
      information from a case report of gastrinoma.

PMID- 20823642
TI  - FAP is a candidate disease in patients with undetermined polyneuropathy.

PMID- 20823643
TI  - Effects of telmisartan on insulin resistance in Japanese type 2 diabetic
      patients.
AB  - OBJECTIVE: PPARgamma agonists are widely used in type 2 diabetic patients to
      reduce insulin resistance. Recently, telmisartan, an AT1 receptor antagonist, was
      reported to function as a partial agonist of PPARgamma based on in vitro
      experiments. The aim of the present study was to investigate whether the
      PPARgamma enhancing activity of telmisartan is exerted clinically in diabetic
      patients. METHODS: We compared the effects of telmisartan with those of
      candesartan, on insulin sensitivity, the serum levels of various adipocytokines
      and oxidative stress. PATIENTS: In total, 85 Japanese type 2 diabetic patients
      with hypertension, maintained on 8 mg per day of candesartan, were randomly
      assigned to the TM group (candesartan switched to 40 mg of telmisartan, n=38) or
      the CD group (no treatment change, n=47). RESULTS: After 3 months, oxidized
      lipids were significantly decreased only in the TM group. Although the
      homeostasis assessment model of insulin resistance (HOMA-R) tended to be improved
      and serum concentrations of HDL-cholesterol and HMW adiponectin tended to be
      increased only in the TM group, these alterations were too small to be
      significant by unpaired t-test. Interestingly, in subgroup analysis, the
      alterations of HOMA-R, serum concentrations of oxidized lipids, and HMW
      adiponectin were more apparent in obese TM group subjects and the changes reached
      statistical significance. CONCLUSION: Switching from candesartan to telmisartan
      in obese subjects increases serum adiponectin and improves both insulin
      resistance and oxidative stress, while these effects were not statistically
      apparent in the total patient population. These results support the idea that
      telmisartan exerts its PPARgamma enhancing activity clinically in obese type 2
      diabetic patients.

PMID- 20823644
TI  - Impact of peripheral lymphocyte count on the sensitivity of 2 IFN-gamma release
      assays, QFT-G and ELISPOT, in patients with pulmonary tuberculosis.
AB  - OBJECTIVE: This study evaluated the effect of peripheral lymphocyte count on 2
      interferon-gamma release assays [QuantiFERON TB-Gold (QFT-G) and enzyme-linked
      immunospot (ELISPOT)] and their sensitivity in patients with pulmonary
      tuberculosis, including HIV-negative immunocompromised patients. PATIENTS AND
      METHODS: Two hundred thirty patients with microbiologically confirmed active
      pulmonary tuberculosis were subjected to the tests. Lymphocyte counts were
      analyzed simultaneously. RESULTS: Overall sensitivity was 74% (159/215; 95% CI,
      68-80%) for QFT-G and 92% (198/215; 89-96%) for ELISPOT (p<0.0001). In patients
      with peripheral lymphocyte counts of > or =1000/microL, sensitivity was high for
      both QFT-G (88%, 111/126; 82-94%) and ELISPOT (97%, 122/126; 94-100%). However,
      the sensitivity decreased significantly with decreasing peripheral lymphocyte
      count for both QFT-G (test for trend p<0.0001) and ELISPOT (test for trend
      p=0.007). When lymphocyte counts were <500/microL, the sensitivity was 81%
      (25/31; 66-96%) for ELISPOT, but only 39% (12/31; 21-57%) for QFT-G. CONCLUSION:
      Both QFT-G and ELISPOT are sensitive methods for detecting active pulmonary
      tuberculosis, but their sensitivity partly depends on peripheral lymphocyte
      counts. At low lymphocyte count conditions, ELISPOT is superior to QFT-G for
      detecting tuberculosis, irrespective of age, gender, and nutrition.

PMID- 20823645
TI  - Amrubicin monotherapy for elderly patients with previously treated lung cancer.
AB  - OBJECTIVE: The novel anthracycline agent amrubicin, has been approved in Japan to
      treat small and non-small cell lung cancers (SCLC and NSCLC). The present study
      evaluates the toxicity and effect of amrubicin especially in elderly patients
      with previously treated lung cancer. PATIENTS AND METHODS: This retrospective
      study analyzed data from 51 patients (<70 years of age, n=29; > oor =70 years of
      age, n=22) with lung cancer (NSCLC, n=21; SCLC, n=30) who were treated with
      amrubicin at our hospital, between July 2003 and October 2009. All patients had
      recurrent or refractory lung cancer after one or more chemotherapy regimens. We
      compared the outcomes of patients younger and older than 70 years of age.
      Amrubicin (30-40 mg/m(2)/day) was infused depending on patient performance status
      and laboratory data over a period of 5 minutes on days 1-3, with courses repeated
      at intervals of at least 3 weeks. The dose was modified according to
      myelosuppression. RESULTS: The mean number of treatment cycles, mean dose and
      mean interval of amrubicin administration did not significantly differ between
      patients aged <70 and > or =70 years. The rate of hematological toxicities (> or
      = Grade 3) also did not significantly differ between the two age groups
      (leukopenia, 48.3% and 59.1% for age <70 and > or =70 years, p=0.573;
      neutropenia, 65.5% vs. 77.3%, p=0.536; anemia, 20.7% vs. 22.7%, p=1.000;
      thrombocytopenia, 13.8% vs. 31.8%, p=0.173). The incidence of grade 2-4 non
      hematological toxicities also did not significantly differ between the groups.
      The response rate of SCLC and disease control rate of NSCLC were similar in the
      younger and older groups. CONCLUSION: Amrubicin monotherapy might be equally
      tolerated by elderly and younger patients. Further studies are needed to
      investigate the benefit of amrubicin monotherapy among elderly patients with
      previously treated lung cancer.

PMID- 20823646
TI  - Radiofrequency energy induced ventricular fibrillation in a case of idiopathic
      premature ventricular contraction originating from the left ventricular papillary
      muscle.
AB  - A 15-year-old boy without structural heart disease was admitted for the treatment
      of frequent episodes of premature ventricular contractions (PVCs). Left
      ventricular mapping revealed that the origin of PVC was at the posterior
      papillary muscle. Diastolic small potentials were observed during sinus rhythm
      with a constant interval following QRS beats. This potential eventually coupled
      with the ventricular myocardium, resulting in the generation of PVC, and thus
      preceded QRS by 31 msec. Catheter ablation to this site induced non-sustained
      ventricular tachycardia, followed by transient ventricular fibrillation. Repeated
      application of radiofrequency energy eliminated PVC accompanied by the split of
      the diastolic potential.

PMID- 20823647
TI  - A lethal case of Plasmodium falciparum infection in a young patient with end
      stage renal failure who underwent regular hemodialysis.
AB  - Acute renal failure associated with Plasmodium falciparum infection is already
      well recognized. Nevertheless, end-stage chronic renal failure and falciparum
      malaria comorbidity is a rare condition. We report a case of Plasmodium
      falciparum infection in a young male Javanese patient with end-stage chronic
      renal failure who underwent regular hemodialysis. This rare comorbidity led to
      rapid deterioration of consciousness and metabolic disturbances which had already
      existed in end-stage renal failure. Because of the immunosuppressive condition
      due to organ failure, the patient did not survive despite anti-malarial
      chemotherapy.

PMID- 20823648
TI  - Foreign body granulomatous change from absorbable gelatin sponge and microcoil
      embolization after a guidewire-induced perforation in the distal coronary artery.
AB  - We report an autopsy case of treatment by absorbable gelatin sponge and microcoil
      embolization after perforation of the distal coronary artery by guidewire.
      Histological examination revealed a foreign body granuloma in the coronary artery
      with embolization. Foreign body reaction to absorbable gelatin sponge seemed to
      be stronger than that to the microcoil.

PMID- 20823649
TI  - Aborted cardiac arrest in a patient carrying KCNE1 D85N variant during the
      postpartum period.
AB  - The postpartum period is associated with an increased risk of fatal ventricular
      tachyarrhythmias in patients with congenital long QT syndrome (LQTS). We describe
      a 20-year-old female with LQTS who experienced aborted cardiac arrest during the
      postpartum period. Genetic screening identified a KCNE1 D85N variant, which has
      been reported to be a LQTS-causing gene variant, in the patient and her younger
      sister, whose QT interval was also prolonged. Since the allele frequency of this
      variant is almost 1%, it may be important to clarify whether such variant
      carriers indeed have an increased risk of fatal ventricular tachyarrhythmias
      during the postpartum period.

PMID- 20823650
TI  - Emphysematous cystitis with diabetic neurogenic bladder.
AB  - A 62-year-old diabetic woman suffering from high fever was admitted to our
      hospital. She had a lower abdominal phantom tumor and hyperglycemia. The results
      of urine analysis showed hematuria and bacteriuria. X-ray and computed tomography
      revealed gas accumulation in the wall of the bladder. Escherichia coli was
      identified in urine culture. On the basis of the lack of urine output and the
      identification of residual urine on catheterization, a diagnosis of emphysematous
      cystitis with diabetic neurogenic bladder was established. The patient recovered
      after discontinuation of urinary drainage, intensive insulin therapy, and
      antibiotic therapy.

PMID- 20823651
TI  - Transient polyuria related to central diabetes insipidus caused by lymphocytic
      infundibulo-neurohypophysitis in a patient treated for Graves' disease.
AB  - A 45-year-old man was hospitalized because of weight loss, finger tremor, thirst,
      polydipsia and increased urinary frequency. He was diagnosed with Graves' disease
      (GD) and central diabetes insipidus (CDI). Magnetic resonance imaging revealed
      the enlarged posterior pituitary with thickened stalk. Histological examination
      obtained from biopsy of the pituitary revealed lymphocytic infundibulo
      neurohypophysitis. He received treatment with thiamazole (MMI) for GD and
      desmopressin acetate (DDAVP) for CDI. However, DDAVP administration could be
      discontinued as GD was gradually improved. This course indicates that not only
      the recovered renal response to arginine-vasopressin but also the
      immunomodulative effects of MMI might attribute to the improvement of polyuria.

PMID- 20823652
TI  - Thrombosis in inferior vena cava due to enlarged renal cysts in autosomal
      dominant polycystic kidney disease.
AB  - We report a rare case of thrombosis in the inferior vena cava (IVC) due to
      enlarged cysts in autosomal dominant polycystic kidney disease. A 71-year-old
      woman visited our hospital with a complaint of rapid left lower extremity
      swelling. Computed tomography (CT) revealed massive thrombosis from the IVC to
      the bilateral common iliac vein. The extrinsic mechanical stress of renal cysts
      to the IVC seemed to have induced thrombosis in the vein that resulted in the
      cause of severe edema in the left lower extremity. Her renal cysts were
      percutaneously punctured for the relief of compression and she received injection
      of 99.5% ethanol for prevention against reaccumulation of cyst fluid after IVC
      filter had been positioned. The edema of her left lower extremity improved
      temporarily, however, follow-up CT two months after cyst puncture showed
      reaccumulation of the fluid. Therefore, excision of the responsible cyst wall by
      open surgery was carried out.

PMID- 20823653
TI  - A case of isolated peripheral pulmonary artery branch stenosis associated with
      multiple pulmonary artery aneurysms.
AB  - Selective right pulmonary arteriography and 3-dimensional computed tomography
      revealed multiple severe stenoses of the peripheral pulmonary artery associated
      with poststenotic aneurysms in a 65-year-old woman. She was referred to the
      hospital for evaluation of dry cough, gradually increasing dyspnea and multiple
      nodular shadows on a chest radiograph. Echocardiography and cardiac
      catheterization showed severe pulmonary hypertension, though other structural
      heart diseases or well-characterized congenital syndromes were ruled out. She was
      diagnosed as isolated peripheral pulmonary artery branch stenosis. Recent
      advances in CT technology enable a less-invasive assessment of pulmonary artery,
      and can be useful in the management of pulmonary arterial hypertension.

PMID- 20823654
TI  - Pandemic (H1N1) 2009-associated ARDS rescued by neuraminidase inhibitors with
      emergency use of extracorporeal membrane oxygenation.
AB  - A 36-year-old man with underlying systemic lupus erythematosus complicated by
      autoimmune hemolytic anemia underwent immunosuppressive treatment. After showing
      a low-grade fever for two days, his fever spiked. He was confirmed to have
      pandemic (H1N1) 2009 by real-time reverse transcription polymerase chain reaction
      (PCR). His condition deteriorated to acute respiratory distress syndrome (ARDS),
      and mechanical ventilation became necessary. The lowest PaO(2)/FIO(2) ratio was
      77, and he was placed on extracorporeal membrane oxygenation (ECMO). Based on our
      observation, the emergency use of ECMO in addition to peramivir might be useful.
      A noteworthy point is that once ARDS deteriorates due to pandemic (H1N1) 2009,
      intensive supportive care should be started.

PMID- 20823655
TI  - Successful allogeneic hematopoietic stem cell transplantation for aggressive NK
      cell leukemia.
AB  - Aggressive natural killer cell leukemia (ANKL) is a highly aggressive
      lymphoproliferative disease. An appropriate therapeutic strategy for ANKL remains
      to be established, but a few case reports have suggested that allogeneic
      hematopoietic stem cell transplantation (allo-HCT) can be curative. Here, we
      report a young woman with ANKL showing central nervous system (CNS) invasion, who
      has been in complete remission for more than a year after allo-HCT following two
      courses of intravenous chemotherapy and several rounds of intrathecal
      chemotherapy. Intensive remission induction chemotherapy followed by conventional
      myeloablative allo-HCT is a promising approach for long-term remission in cases
      of this aggressive malignancy.

PMID- 20823656
TI  - Rheumatoid leptomeningitis: radiological alteration of cerebral hypoperfusion and
      subarachnoid lesions.
AB  - A 56-year-old man with rheumatoid arthritis developed emotional lability and
      myoclonic seizure in the left arm, followed by fever and generalized convulsion.
      Brain magnetic resonance imaging (MRI) revealed leptomeningeal lesions with
      abnormal enhancement. MRI lesions were localized predominantly in the right
      cerebral subarachnoid spaces. Electroencephalogram showed epileptogenic focus at
      the right frontal and central points. After administration of valproate sodium
      improved convulsion and myoclonus, single photon emission computed tomography
      (SPECT) using N-isopropyl-p-(123)I-iodoamphetamine was performed. Brain SPECT
      displayed hypoperfusion predominantly in the right cerebral hemisphere.
      Cerebrospinal fluid (CSF) disclosed mild pleocytosis and marked elevations of
      interleukin-6 levels. Repeated CSF analyses showed cytology of class I and
      negative results for infectious pathogens. Methylprednisolone pulse therapy (1 g
      for 3 days, iv) and subsequent prednisolone administration (daily 50 mg, po)
      ameliorated neurological symptoms dramatically. Prednisolone was tapered to 20
      mg/day for 5 months. Leptomeningeal MRI lesions were attenuated gradually
      followed by restoration of cerebral hypoperfusion on SPECT. He was diagnosed as
      rheumatoid leptomeningitis (RLM). Although clinical features of RLM exhibited
      variable deficits of the central nervous system (CNS), MRI failed to detect the
      corresponding CNS lesions. We first highlighted neuroradiological changes of
      cerebral hypoperfusion and leptomeningeal lesions in RLM. These neuroimages of
      our patient supported that leptomeningeal inflammation and the adjacent
      cerebrocortical ischemia could cause encephalitis-like symptoms in RLM patients.

PMID- 20823657
TI  - Bilateral basal ganglia lesions in a hemodialysis patient.

PMID- 20823658
TI  - POEMS syndrome, congestive heart failure and thalidomide -food for thought.

PMID- 20823660
TI  - Feature on erythropoiesis in dietary restricted rats.
AB  - We attempted to characterize the influence of undernutrition on erythropoiesis in
      toxicity studies. Male rats were divided into the following 5 groups: dietary
      restriction groups in which feeding was restricted by 33% or 66% for 14 days (R33
      and R66); phlebotomy groups in which 1% or 4% of total blood volume was removed
      by serial phlebotomy for 14 days (PB01 and PB04); and a nontreated group (NT).
      Toxicological parameters such as hematology and blood chemistry were evaluated.
      The body weight gains in the R33 and phlebotomy groups (PB01 and PB04) were
      similar and were less than that observed in the NT group. Decreases in peripheral
      blood reticulocytes, bone marrow erythroids and the unsaturated iron binding
      capacity (UIBC) were observed as changes that suppressed erythropoiesis in the
      R33 and R66 groups. However, increases in reticulocytes and UIBC were observed as
      opposite changes in the phlebotomy groups. In addition, an increase in the blood
      urea nitrogen level and a decrease in the serum alkaline phosphatase level were
      observed as changes reflecting poor nutrition in the phlebotomy groups. Decreased
      reticulocytes which are related to poor nutrition were not observed. However,
      increases in those cells as reflected by a loss of blood were observed in the
      phlebotomy groups. Even if undernutrition suppresses erythropoiesis, the ability
      of erythropoiesis to respond to a demand appears to be retained. In repeated dose
      toxicity studies, decreased food consumption is often observed in the drug
      administration groups. Our study results provide useful information for
      hematological evaluations in toxicity studies.

PMID- 20823662
TI  - Progression of glomerulonephritis to end-stage kidney disease in a cat with
      nephrotic syndrome.
AB  - A percutaneous renal biopsy was performed on a 3-year-old female Japanese
      domestic cat with pleural effusion, mild azotemia, hypoalbuminemia,
      hypercholesterolemia, and proteinuria. Glomerular lesions included mild diffuse
      hypercellularity and numerous capsular adhesions with segmental
      sclerosis/hyalinosis of glomerular tufts. Electron microscopy revealed many
      subendothelial dense deposits with characteristic outer protrusion of glomerular
      basement membrane. Diffuse and global granular deposits of IgG and C3 were
      detected along the capillary walls. Tubulo-interstitial changes were mild at the
      time of biopsy, but progression of the disease was predicted because of the many
      capsular adhesions of the glomerular tufts. The cat was fed a prescription diet
      without any other specific or symptomatic therapy after renal biopsy, and died 43
      weeks after the biopsy. At necropsy, extensive tubulo-interstitial fibrosis and
      mononuclear cell infiltration had developed throughout the cortex and outer
      medulla, and most glomeruli had extensive global sclerosis or obsolescence with
      less prominent depositions of IgG and C3.

PMID- 20823663
TI  - Therapeutic changes of plasma N-terminal pro-brain natriuretic peptide
      concentrations in 9 dogs with patent ductus arteriosus.
AB  - The plasma N-terminal proBNP (NT-proBNP) concentration is measured for
      determining the diagnosis and severity of heart failure in dogs. However, it is
      still unclear whether measurements of circulating NT-proBNP levels provide
      clinical utility as an indicator of therapeutic efficacy. Thus, we investigated
      the surgical correction-related changes of plasma NT-proBNP concentrations in 9
      dogs with patent ductus arteriosus (PDA). Physical examination, thoracic
      radiography and echocardiography were conducted both before and after surgery.
      Similarly, the plasma NT-proBNP concentrations were determined using an enzyme
      immunoassay for canine pro-BNP. The International Small Animal Cardiac Health
      Council (ISACHC) class and murmur grade were significantly improved after surgery
      compared with before surgery. Vertebral heart size (VHS) and cardiothoracic ratio
      (CTR) were significantly decreased after surgery. Fractional shortening was
      significantly decreased and relative wall thickness (RWT) was significantly
      increased after surgery. Furthermore, the plasma NT-proBNP concentrations were
      significantly decreased by surgical correction. The plasma NT-proBNP
      concentration showed significant positive correlation with the ISACHC class,
      murmur grade, VHS and CTR and significant negative correlation with the RWT.
      Therefore, measurement of plasma NT-proBNP levels can be used to monitor the
      effectiveness of therapies such as surgical correction of PDA.

PMID- 20823664
TI  - Plasma growth hormone is elevated immediately after resistance exercise with
      electrical stimulation and voluntary muscle contraction.
AB  - Resistance exercise is a physiological stimulus for acute increases in growth
      hormone (GH) secretion, and it also causes lactate accumulation and stimulates
      norepinephrine (NE) secretion as a sympathetic nervous response. The hybrid
      exercise method (HYB) is a novel resistance exercise method that combines a
      voluntary concentric muscle contraction and an electrically stimulated eccentric
      muscle contraction. This study was designed to compare the hormonal responses of
      HYB with typical weight training (WT), as regards GH, lactate, and NE. Twenty
      four healthy male subjects (20-27 years) were divided into the HYB group and the
      WT group. All the subjects performed bilateral leg exercises with 10 sets of 10
      reciprocal 2-second (45 degrees /sec) knee flexion-and-extension contractions,
      and with 1-min interset rest intervals. Plasma concentrations of GH, lactate, and
      NE were determined before exercise and immediately after exercise (0 min) as well
      as at 15, 30, 60, and 120 min. The plasma concentrations of GH and lactate were
      significantly increased immediately after HYB or WT (P < 0.05). Moreover, the
      degree of the increases of GH and lactate after HYB was significantly higher than
      that after WT (P < 0.05). The plasma concentration of NE was significantly
      increased after HYB or WT (P < 0.01), but no significant difference was observed
      between the two groups. These results indicate that HYB is more efficient in
      stimulating acute increases in plasma GH and lactate without enhancing
      sympathetic nerve stimulation, compared to WT. Therefore, HYB may be an effective
      countermeasure to muscle disuse associated with bed rest or spaceflight.

PMID- 20823665
TI  - Cardio-ankle vascular index for evaluating immunosuppressive therapy in a patient
      with aortitis syndrome.
AB  - Aortitis syndrome is a chronic vasculitis that leads to arterial wall thickening
      and stiffening in large elastic arteries. However, there are no established
      markers for assessing arterial stiffening in aortitis syndrome. The cardio-ankle
      vascular index (CAVI) has recently been utilized to assess arterial stiffening
      that is associated with atherosclerosis-related diseases. We hypothesized that
      CAVI can be applicable for assessing alterations in arterial stiffness during
      immunosuppressive therapy for aortitis syndrome. A 69-year-old woman with a 2
      month history of recurrent fever, fatigue, and malaise, showed intense 18F
      fluorodeoxyglucose (18F-FDG) uptake in the thoracic aorta and common carotid
      arteries in 18F-FDG-positron emission tomography. These clinical and imaging
      findings resulted in the diagnosis of aortitis syndrome. The patient also showed
      the elevated CAVIs on both sides (right, 10.3; left, 10.4) (normal value for her
      age, 9.1 +/- 0.8), indicating the arterial stiffness due to aortitis syndrome.
      The patient was treated for 34 weeks with immunosuppressive therapy, which
      included oral prednisolone and methotrexate. C-reactive protein (from 4.24 to
      0.49 mg/dL) and immunoglobulin G (from 2,627 to 1,524 mg/dL) were decreased by 7
      weeks after initiation of the treatment. The decrease in these inflammatory
      parameters suggests the effectiveness of the immunosuppressive therapy. In
      addition, after the 34-week treatment, the CAVIs on both sides (right, 9.3; left,
      9.2) were within the normal range. These data indicate that the immunosuppressive
      therapy ameliorates the degree of arterial stiffness. In conclusion, CAVI may be
      a promising marker for evaluating the effectiveness of immunosuppressive therapy
      in patients with aortitis syndrome.

PMID- 20823666
TI  - A high-throughput biotin-avidin-ELISA for studying expression of platelet
      membrane glycoproteins and its clinical application.
AB  - Platelet membrane glycoproteins (GPs) are critical for normal platelet adhesion,
      activation and aggregation. To define the abnormalities in surface GP expression
      on circulating platelets and provide a better biomarker of bleeding and
      thrombotic disorders, we have developed a accurate, time-saving and high
      throughput biotin-avidin enzyme-linked immunosorbent assay (BA-ELISA) with the
      monoclonal antibodies (mAbs), 7E3 against the complex of GPIIb and GPIIIa
      (GPIIb/IIIa), SZ-51 against P-selectin, and SZ-2 against GPIb, respectively. The
      levels of P-selectin and GPIIb/IIIa were measured in patients with acute
      myocardial infarction (AMI), intracerebral hemorrhage (ICH), or diabetes mellitus
      (DM)) and healthy subjects. Inhibition of GP expression was evaluated with SZ-21,
      an inhibitory mAb against GPIIIa and aspirin, respectively. The sensitivity of BA
      ELISA is high enough to detect platelet count as low as 3.13 x 10(9)/L in
      platelet-rich plasma (PRP). Both the inter-assay and intra-assay coefficient
      variation are less than 10%. Adenosine diphosphate (ADP)-induced or non-ADP
      induced expression of P-selectin and GPIIb/IIIa was significantly higher in AMI,
      ICH or DM than that in controls (P < 0.01 for each). Either SZ-21 or aspirin can
      inhibit the ADP-induced expression of P-selectin and GPIIb/IIIa. Importantly, a
      high correlation was detected between BA-ELISA and flow cytometry methods. These
      observations indicate that BA-ELISA is a sensitive and high-throughput assay for
      evaluating platelet GP expression. The newly developed BA-ELISA can be
      popularized in community hospitals, because it does not require sophisticated
      equipments and reagents. This method is suitable for screening inhibitors of
      platelet activation and has a potential in use for diagnostic purposes.

PMID- 20823667
TI  - [Development of novel delivery systems of drugs for the treatment of diabetes and
      osteoporosis].

PMID- 20823668
TI  - [Enhancement of insulin absorption through mucosal membranes using cationic
      polymers].
AB  - Cationic polymers (e.g., cationated gelatins, cationated pullulans and poly-L
      arginines) have potential to promote transmucosal delivery of peptide and protein
      drugs without producing any toxic effects on epithelial cells. These cationic
      polymers could interact with the mucosal membranes and increase the number of
      pathways for water-soluble macromolecules in the tight junctions. In the case of
      insulin having negative charges in neutral solutions, interaction between the
      cationic polymers and insulin is also important to promote suitable delivery. An
      appropriate interaction can help insulin to access to cell surface, but too
      strong interaction suppresses insulin absorption. When the absorption-enhancing
      effects of sperminated pullulans and gelatin having different numbers of amino
      groups on the pulmonary absorption of insulin in rats were evaluated, their
      enhancing effects correlated with the amino group content. Cationic polymers
      having suitable charge density will be useful for pulmonary delivery systems of
      insulin.

PMID- 20823669
TI  - [Improvement of intestinal absorption of poorly absorbable drugs by
      polyamidoamine (PAMAM) dendrimers as novel absorption enhancers].
AB  - The intestinal absorption of hydrophilic drugs and macromolecular drugs is
      generally limited by their poor membrane permeability characteristics in the
      intestine. Therefore, absorption enhancers were usually adopted for improving the
      intestinal absorption of these poorly absorbable drugs. However, conventional
      absorption enhancers were generally more effective in the large intestine rather
      than the small intestine and absorption enhancers with high effectiveness in the
      small intestine is highly desirable. Based on the background, we focused on
      polyamidoamine (PAMAM) dendrimers as novel absorption enhancers and effects of
      PAMAM dendrimers on the intestinal absorption of poorly absorbable drugs were
      examined by an in situ closed loop method in rats. The absorption of 5(6)
      carboxyfluorescein (CF), fluorescein isothiocyanate-dextran with an average
      molecular weight of 4000 (FD4) and calcitonin from the rat small intestine was
      significantly enhanced in the presence of PAMAM dendrimers. However, PAMAM
      dendrimers had almost no absorption enhancing effect on the small intestinal
      absorption of macromolecular drugs including fluorescein isothiocyanate-dextran
      with an average molecular weight of 10000 (FD10) and insulin. Furthermore, we
      evaluated the intestinal membrane damage with or without PAMAM dendrimers. PAMAM
      dendrimers at concentrations of 0.05% (w/v) and 0.1% (w/v) did not increase the
      activities of lactate dehydrogenase (LDH) and amounts of protein in the
      intestine. These findings suggested that PAMAM dendrimers at lower concentrations
      might be potential and safe absorption enhancers for improving absorption of
      poorly absorbable drugs from the small intestine.

PMID- 20823670
TI  - [Development of delivery system of bisphosphonates for the treatment of
      osteoporosis].
AB  - Bisphosphonates are carbon-substituted pyrophosphate (PCP) analogues that exhibit
      high affinity to hydroxylapatite and inhibit bone resorption after their
      administration. They are widely used as the first-choice drug for the treatment
      and prevention of bone diseases, including Paget's disease, hypercalcemia of
      malignancy, and osteoporosis. However, the oral bioavailability of
      bisphosphonates is quite low (1-2%). In addition, the oral administration of
      bisphosphonates has been associated with mucosal damage, including gastritis,
      gastric ulcer, and erosive esophagitis. Therefore, it is highly desirable to
      develop new delivery systems that improve their bioavailability and safety. In
      this review, recent challenges in the developments of novel delivery system of
      bisphosphonates are summarized. Then, future developments of delivery system of
      bisphosphonates are also discussed in order to improve their therapeutic efficacy
      and safety in the treatment of bone diseases.

PMID- 20823671
TI  - [Absorption of calcitonin in oral and pulmonary administration with polymer
      coated liposomes].
AB  - We have developed polymer-coated liposomes for effective and non-invasive
      delivery of peptide drugs. Polymer-coated liposomes, which are liposomal
      particles coated with functional polymers, were designed in order to have
      suitable functions required for drug delivery. So far, we have reported prolonged
      retention in the gastro-intestinal tract owing to the mucoadhesive properties of
      the polymer-coated liposomes. This review shows outline of effectiveness of
      polymer-coated liposomes in absorption of calcitonin after oral administration.
      The main factors for absorption enhancing of calcitonin are mucoadhesion and
      penetration of polymer-coated liposomes into the mucus layer. Application of
      polymer-coated liposomes in pulmonal drug delivery and novel strategies for
      designing mucoadhesive particulate systems are also described.

PMID- 20823672
TI  - [Application of mercury-resistant genes in bioremediation of mercurials in
      environments].
AB  - Mercury and its organic compounds, especially methylmercury are extremely
      hazardous pollutants that have been released into the environment in substantial
      quantities by natural events and anthropogenic activities. Due to the acute
      toxicity of these contaminants, there is an urgent need to develop an effective
      and affordable technology to remove them from the environments. Recently,
      attempts have been made to utilize bacterial mer operon-mediated reduction and
      volatilization of mercurials for environmental remediation of mercury pollution.
      However, application of this technology to the treatment of mercury-contaminated
      environments has been limited by social concerns about the release of volatile
      mercury that will become part of the local mercury cycle and repollute the
      environment again, into the ambient air. To improve this environmental problem, a
      new mercury scavenging mechanism that could be expressed in living cells and
      accumulates mercury from contaminated site without releasing mercury vapor is
      necessitated. To construct a new biocatalyst that is capable of specifically
      accumulating mercury from contaminated sites without releasing mercury vapor, we
      have genetically engineered bacteria and tobacco plant for removal of mercury
      from wastewater and soils, respectively, to express a mercury transport system
      and organomercurial lyase enzyme simultaneously, and overexpress polyphosphate, a
      chelator of divalent metals. The applicability of these new engineered
      biocatalysts in the environmental remediation of mercurials is evaluated and
      discussed in this review.

PMID- 20823673
TI  - [Formation mechanism and chemical safety of nonintentional chemical substances
      present in chlorinated drinking water and wastewater].
AB  - This paper reviews the formation mechanism and chemical safety of nonintentional
      chemical substances (NICS) present in chlorine-treated water containing organic
      contaminants. Undesirable compounds, i.e., NICS, may be formed under certain
      conditions when chlorine reacts with organic matter. The rate and extent of
      chlorine consumption with organics are strongly dependent on their chemical
      structures, particularly whether double bonds or sulfur and nitrogen atoms occur
      in the molecules. Organothiophosphorus pesticides (P=S type) are easily oxidized
      to their phosphorus compounds (P=O type) in chlorinated water containing HOCl as
      little as 0.5 mg/l, resulting in an increase in cholinesterase-inhibitory
      activity. Chlorination of phenols in water also produces a series of highly
      chlorinated compounds, including chlorophenols, chloroquinones, chlorinated
      carboxylic acids, and polychlorinated phenoxyphenols (PCPPs). In some of these
      chloroquinones, 2,6-dichloroalkylsemiquinones exhibit a strong mutagenic response
      as do positive controls used in the Ames test. 2-phenoxyphenols in these PCPPs
      are particularly interesting, as they are present in the chlorine-treated phenol
      solution and they are also precursors (predioxins) of the highly toxic
      chlorinated dioxins. Polynuclear aromatic hydrocarbons (PAHs) were found to
      undergo chemical changes due to hypochlorite reactions to give chloro-substituted
      PAHs, oxygenated (quinones) and hydroxylated (phenols) compounds, but they
      exhibit a lower mutagenic response. In addition, field work was performed in
      river water and drinking water to obtain information on chemical distribution and
      their safety, and the results are compared with those obtained in the model
      chlorination experiments.

PMID- 20823674
TI  - [Functional glutamate signaling in bone].
AB  - L-glutamate (Glu) has been thought to be an excitatory amino acid
      neurotransmitter in the mammalian central nervous system. Relatively little
      attention has been paid to the functional expression of Glu signaling machineries
      in peripheral tissues. In this review, therefore, we summarized the possible
      signaling by Glu as an extracellular signal mediator in mechanisms underlying
      maintenance of cellular homeostasis in bone tissues. Constitutive expression of
      mRNAs for particular Glu receptors (GluR), Glu transporters (GluT) was found in
      osteoblasts. N-methyl-D-aspartic acid receptor antagonist MK-801 significantly
      prevented differentiation and maturation of osteoblasts through modulation of
      expression of Runx2. DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid
      significantly increased the release of endogenous Glu from osteoblasts through
      its receptor expressed by osteoblasts. In addition, [3H]Glu uptake was also seen
      in a temperature- and sodium-dependent manner with pharmacological profiles
      similar to those for brain GluTs in osteoblasts. Although no mRNA expression was
      found for all GluRs examined in primary cultured mouse osteoclasts, constitutive
      expression of mRNAs was seen with GluT, such as excitatory amino acid
      transporters and cystine/Glu antiporter. Glu markedly inhibited
      osteoclastogenesis in a manner sensitive to the antiporter inhibitor. The
      systemic administration of Glu significantly prevented the decreased bone mineral
      density in addition to increased osteoclastic indices in ovariectomized mice in
      vivo. Taken together, Glu could play a pivotal role in mechanisms underlying the
      maintenance of cellular homeostasis as an extracellular signal mediator in bone.

PMID- 20823675
TI  - [Recent studies on gas sensors, CooA, FixL, and Dos].
AB  - Heme-containing proteins, the heme proteins, are known to have physiologic
      functions in humans, mammalians, fish, plants, and bacteria. For example,
      hemoglobin and myoglobin, which belong to the globin family, have been studied in
      terms of their structures and functions with spectroscopic and mutagenic methods.
      Recently, a new class of heme proteins has been discovered, referred to as gas
      sensors. These are heme-based sensor proteins that play important roles in
      transcriptional activation, histidinekinase activities, phosphodiesterase
      activities, etc. CooA is a CO-sensing transcriptional activator derived from the
      photosynthetic bacterium Rhodospirillum rubrum. FixL is a rhizobial oxygen sensor
      protein, and we have targeted Bj FixL derived from Bradyrhizobium japonicum. Dos
      from Escherichia coli is an oxygen sensor protein, which senses oxygen in the
      heme-containing domain and induces phosphodiesterase activity in other domains.
      In previous work, we studied the axial ligands and C-helix of CooA to clarify the
      activation mechanism. Moreover, FixL and Dos were investigated using time
      resolved spectroscopic methods. Whereas FixL has a pentacoordinate heme in the
      ferrous deoxy form, there are a proximal histidine (His 77) and a distal
      methionine (Met 95) as axial ligands to coordinate to the heme iron in EcDos.
      However almost all gas sensors show mono-exponential rebinding (6-7 ps), while
      EcDosH and full-length Dos show biexponential rebinding (7 ps and 35 ps) on the
      internal ligand. The results were also supported by molecular dynamic simulation.
      Here we discuss recent work on gas sensors with implications provided by our
      research.

PMID- 20823676
TI  - [Regeneration of perivascular nerve and role of angiotensin receptors].
AB  - The present study was designed to investigate involvement of angiotensin (Ang) II
      type 2 receptors (AT2R) in restoration of perivascular nerve innervation injured
      by topical phenol treatment. Male Wistar rats underwent in vivo topical
      application of 10% phenol around the superior mesenteric artery to induce nerve
      injure. Phenol treatment markedly reduced densities of both calcitonin gene
      related peptide (CGRP)-like immunoreactivity (LI)- and neuropeptide Y (NPY)-LI
      containing fibers. NGF restored densities of both nerve fibers to the Sham
      control level. Coadministration of Ang II and losartan (AT1R antagonist)
      significantly increased the density of CGRP-LI-fibers but not NPY-LI-fibers
      compared with saline control. The increase of the density of CGRP-LI-fibers by
      coadministration of Ang II and losartan was suppressed by adding PD123319 (AT2R
      antagonist). Furthermore, NGF-induced CGRP-LI nerve regeneration was inhibited by
      PD123319 treatment. NGF-induced increase of AT2R mRNA level was significantly
      suppressed by AT1R antagonist treatment in phenol treated rats dorsal root
      ganglia. These results suggest that selective stimulation of AT2R by Ang II
      facilitates reinnervation of mesenteric perivascular CGRP-containing nerves
      injured by topical phenol application in the rat.

PMID- 20823677
TI  - [Practical study for seminar program certified by Japanese Society of Hospital
      Pharmacists for Clinical Psychiatric Pharmacists organized by Chiba Society of
      Hospital Pharmacists, and investigation of participants' background and issues
      for taking board certified psychiatric pharmacy specialists and board certified
      pharmacists in psychiatric pharmacy certifications using questionnaires].
AB  - Recently, certification systems for Board-Certified Psychiatric Pharmacy
      Specialists (BCPPS) and Board-Certified Pharmacists in Psychiatric Pharmacy
      (BCPPP) were established by the Japanese Society of Hospital Pharmacists (JSHP)
      in 2008, to meet the increasing needs for specialists in psychiatric pharmacy.
      However, there was no report on the background and opinion of pharmacists who
      have intention to take the BCPPS or BCPPP and/or seminar programs for BCPPS or
      BCPPP. The Chiba Society of Hospital Pharmacists has started to provide a seminar
      program certified by the JSHP to study psychiatry for pharmacists and also
      investigated the participants' background, demand for the program, and issues in
      taking the BCPPS or BCPPP using questionnaires. We found that many participants
      wanted lectures to obtain information on issues they face in routine work as well
      as for certification testing. For many participants, satisfying the requirements
      for applying for the BCPPS or BCPPP was one of the most important issues in
      receiving the qualifications. We found that over 40% of participants working at
      community pharmacies intended to take the BCPPS or BCPPP, although working
      experience at a community pharmacy does not entitle them to apply for the BCPPS
      or BCPPP. The intention of community pharmacists indicates that discussion of the
      requirements for BCPPS or BCPPP certification systems is necessary to improve
      psychiatric community care. We will plan a practical seminar program with
      feedback from this investigation.

PMID- 20823678
TI  - Establishment of a novel model for studying the effects of extracts of Chinese
      herb medicine on human type II 5alpha-reductase in vitro.
AB  - Human steroid 5alpha-reductase type II (hSRD5A2) and dihydrotestosterone (DHT)
      play important roles in benign prostatic hyperplasia (BPH). The aim of our study
      was to establish a novel model to investigate the inhibitory effects of extracts
      and compounds of Chinese herb medicine on hSRD5A2. The gene, hSRD5A2, was
      artificially synthesized and cloned into pcDNA3.1(+) vector, which was
      transfected into CHO cells by liposome. Transfected cells were screened through
      G418 and MTX. The expressed protein of hSRD5A2 by cells was purified and detected
      by western blotting. A minimum reactive system comprising hSRD5A2 and
      testosterone (T) as substrate together with NADPH as hydrogen donor was
      established for screening inhibitors of hSRD5A2. The reaction system was
      optimized in the concentrations of T, NADPH, and hSRD5A2 and reaction
      temperature, time, and activity of hSRD5A2 were determined by the production of
      DHT. Furthermore, we screened some extracts and compounds of Chinese herb
      medicine using this model. The concentrations of T, NADPH, and hSRD5A2 were 0.02
      microM, 0.8 mM, and 0.05 U/microl, respectively, in the model; maximum activity
      of hSRD5A2 was achieved at 37 degrees C and 60 min reaction, and mangiferin had
      significant inhibitory effect on the activity of hSRD5A2. The model in this study
      is convenient and reliable for screening and evaluation of inhibitors of hSRD5A2;
      mangiferin may be a potential medicine for the treatment of BPH.

PMID- 20823679
TI  - [Development and analyses of evaluation criteria for meta-analysis-relationship
      between renin-angiotensin system inhibitor and diabetes mellitus].
AB  - In recent years, evidence-based medicine is practiced in medical care, and meta
      analysis is positioned as the highest quality research paper. However, there are
      no unified criteria to evaluate meta-analysis. Thus, we developed and evaluated
      objective criteria of meta-analysis paper. Meta-analysis was evaluated from the
      standpoint of format and quality. Format score was developed based on QUOROM
      statement. Quality scores were evaluated in each step of meta-analysis. We
      evaluated meta-analysis for advantageous or adverse effect in the relationship
      between Renin-angiotensin system (RAS) inhibitor and diabetes mellitus. Research
      articles either in English or Japanese were searched in PubMed and the Cochrane
      Library in July 2009. Fifty-five studies were evaluated for format and quality
      score. Format score was 64.5+/-25.3% (Mean+/-S.D.), and quality score was 57.1+/
      21.6%. After plotting each score along the X-Y coordinate, format score was
      correlated with quality score (R2=0.702, p<0.001). In studies with quality score
      of 70% or higher, RAS inhibitor prevented new-onset diabetes mellitus.
      Angiotensin converting enzyme (ACE) inhibitor reduced risk of myocardial
      infarction, however, angiotensin receptor blockers (ARB) increased the incidence
      in odds ratio 1.21 (95%CI: 1.04-1.40). We evaluated meta-analysis by format and
      quality score, and these factors showed correlation. Therefore, assessment of
      quality score leads to prompt and reliable evaluation of meta-analysis. According
      to articles evaluated by quality score, RAS inhibitor showed effectiveness on
      diabetes mellitus. However, careful attention must be given in ARB therapy on
      patients with myocardial infarction risk.

PMID- 20823680
TI  - Formulation and development of matrix tablets of tramadol using katira gum as
      release modifier.
AB  - The present study was aimed to study the drug release retardant property of
      katira gum in matrix tablets containing tramadol as a model drug. Katira gum was
      characterized in terms of pH, viscosity and swelling index. The tablets were
      evaluated for various physical tests viz. hardness, friability, tensile strength
      and drug content. In vitro dissolution studies were performed and different
      empirical models were applied to drug release data for evaluating the drug
      release mechanisms and kinetics. Owing to good swelling properties (swelling
      index 340% and 480% after 6 and 24 h hydration) of the gum, the n values (as
      computed from Korsmeyer-Peppas model) were found to be ranging between 0.453 to
      0.710 indicating involvement of both polymeric hydration and relaxation in the
      diffusion of drug from the matrix tablet.

PMID- 20823681
TI  - [Detection of adverse drug reactions with the use of a simple questionnaire].
AB  - In order to detect adverse events in patients at pharmacies, a questionnaire was
      developed to evaluate adverse drug reactions that may come from the use of
      pharmaceuticals. The questionnaire enabled pharmacists to assume possible adverse
      drug reactions while they dispense a prescription but was designed not to make
      patients sensitive. An investigation method was developed to detect adverse drug
      reactions that may be attributable to drug treatment by leading patient natural
      complaints while pharmacists provide drug treatment guidance to patients. This
      investigation was conducted at six pharmacies. As a result, 26.6% of the adverse
      drug reactions that can be associated with the question items ticked by at least
      five patients who had received the same drug were not indicated in the
      precautionary statements of the drugs. This suggests that this investigation may
      possibly contribute to detection of unknown adverse drug reactions. Furthermore,
      some of the patients who ticked question items related to prodromal symptoms of
      serious adverse drug reactions had received drug therapies that were known to be
      associated with those adverse drug reactions. This also suggests that the
      investigation may possibly contribute to detection of serious adverse drug
      reactions. It was considered to be more effective to focus on detection of
      serious adverse drug reactions with the use of the questionnaire in the future,
      which is more important than safety precautions. The accuracy in judging adverse
      drug reactions can be enhanced by asking patients with chronic diseases to
      respond to the questionnaire every time a prescription is dispensed.

PMID- 20823683
TI  - Is Europe really battling obesity?

PMID- 20823682
TI  - Amelioration of dextran sulfate sodium-induced chronic colitis by sulfasalazine
      salicylazosulfapyridine via reducing NF-kappaB transcription factor p65
      recruitment to ICAM-1 gene promoters.
AB  - Sulfasalazine salicylazosulfapyridine (SASP), consisting of 5-aminosalicylic acid
      bound to sulfapyridine by a diazo bond, is an effective drug in the treatment of
      inflammatory bowel diseases (IBD). However, its mechanism of action remains a
      matter of debate. The objective of our work was to investigate SASP's effect on
      NF-kappaB signal transduction pathway in transcriptional regulation level.
      Repeated colitis was induced by administration of 4 cycles of 4% dextran sulfate
      sodium (DSS); The severity of colitis was assessed on the basis of clinical
      signs, colon length, and histology scores. Moreover, sIgA and haptoglobin (HP)
      were analyzed by enzyme linked immunosorbent assay, and ICAM-1 gene expression
      was analyzed by quantitative reverse transcriptase real-time polymerase chain
      reaction (qRT-PCR) using SYBA green I. NF-kappaB signal transduction proteins and
      transcriptional factor p65 interaction with promoter of ICAM-1 were assessed by
      western blotting and chromatin immunoprecipitation assay. SASP administration
      significantly attenuated the colitis signs and caused substantial reductions of
      HP expression, and maintained the level of cecum sIgA. SASP inhibited ICAM-1 gene
      expression and had no effect on MIF gene expression. Also, SASP was able to
      reduce p-IkBalpha protein expression; however, no change in the activation of
      IKKalpha, IKKbeta, p65, and IKBalpha was noted. SASP inhibited p65 recruitment to
      the gene ICAM-1 promoter. In conclusion, inhibition of NF-kappaB pathway signal
      proteins and blockade of p65 binding to gene ICAM-1 promoter might explain the
      effect and mechanisms of SASP at alleviating DSS-induced colitis in mice.

PMID- 20823684
TI  - The assessment of side effects of health recommendations given to youth in
      general and children and adolescents with obesity.

PMID- 20823685
TI  - Are overweight and obese youth at increased risk for physical activity injuries?
AB  - OBJECTIVE: To determine whether relationships between physical activity and
      physical activity injuries are modified by BMI status in youth. METHOD: Data were
      obtained from the 2006 Canadian Health Behaviour in School-Aged Children survey;
      a representative study of 7,714 grade 6-10 youth. A sub-sample of 1,814 were re
      administered the survey in 2007. Analyses considered relationships among the
      major variables in theory-driven cross-sectional and longitudinal analyses.
      RESULT: Among normal weight youth, cross-sectional analyses indicated that those
      who reported high levels of physical activity outside of school experienced 2.28
      (95% confidence interval 1.95-2.68) the relative odds for physical activity
      injury in comparison to those with low levels of physical activity outside of
      school. Analogous odds ratios for overweight and obese youth were 1.89 (1.31
      2.72) and 3.72 (1.89-7.33), respectively. BMI status was not an effect modifier
      of the relationship between physical activity and physical activity injury.
      Similar observations were made in the confirmatory longitudinal analyses.
      CONCLUSION: Concerns surrounding the design of physical activity programmes
      include side-effects such as injury risk. This study provides some re-assurance
      that physical activity participation relates to injury in a consistent manner
      across BMI groups.

PMID- 20823686
TI  - Pharmaceutical quality of nine generic orlistat products compared with
      Xenical(r).
AB  - OBJECTIVE: To compare the pharmaceutical quality of Xenical (chemically produced
      orlistat) with nine generic products, each produced by fermentation processes.
      METHODS: Xenical 120 mg capsules (Roche, Basel, Switzerland) were used as
      reference material. Generic products were from India, Malaysia, Argentina,
      Philippines, Uruguay, and Taiwan. Colour, melting temperature, crystalline form,
      particle size, capsule fill mass, active pharmaceutical ingredient content,
      amount of impurities, and dissolution were compared. Standard physical and
      chemical laboratory tests were those developed by Roche for Xenical. RESULTS: All
      nine generic products failed the Xenical specifications in four or more tests,
      and two generic products failed in seven tests. A failure common to all generic
      products was the amount of impurities present, mostly due to different by
      products, including side-chain homologues not present in Xenical. Some impurities
      were unidentified. Two generic products tested failed the dissolution test, one
      product formed a capsule-shaped agglomerate on storage and resulted in poor
      (</=15%) dissolution. Six generic products were powder formulations. CONCLUSIONS:
      All tested generic orlistat products were pharmaceutically inferior to Xenical.
      The high levels of impurities in generic orlistat products are a major safety and
      tolerability concern.

PMID- 20823687
TI  - Physical activity in normal-weight and overweight youth: associations with weight
      teasing and self-efficacy.
AB  - OBJECTIVE: To examine self-reported physical activity with regard to weight
      teasing and self-efficacy. METHODS: Within a cross-sectional study, 321
      overweight and normal-weight students, consisting of 51% girls (n = 161) and 49%
      boys (n = 160) at a mean age of 12.22 years (SD = 1.07), were sampled from German
      secondary schools. The Perception of Teasing Scale, the Physical Self-Efficacy
      Scale, and the Leipzig Lifestyle Questionnaire for Adolescents were used to
      assess experiences with weight-related teasing, self-efficacy, physical activity
      and social context variables. RESULTS: Self-efficacy, weight teasing and social
      context variables were related to physical activity within the full sample (R(2)
      = 0.433). More frequent weight teasing was associated with decreased physical
      activity in boys, but not in girls. Overweight participants reported more
      frequent weight teasing experiences and less self-efficacy than participants of
      normal weight (all p < 0.001), but there was no difference in physical activity
      (p > 0.05).There were large correlations between self-efficacy and physical
      activity (r = 0.614, p < 0.01), and medium correlations for male sex and physical
      activity (r = 0.298, p < 0.01). Weight teasing and self-efficacy were negatively
      correlated (r = -0.190, p < 0.05). CONCLUSIONS: These results suggest that self
      efficacy and an encouraging social context are beneficial to physical activity
      while weight teasing experiences are detrimental. Interventions against weight
      teasing in youth are needed.

PMID- 20823688
TI  - Expression of neuropeptide Y, omentin and visfatin in visceral and subcutaneous
      adipose tissues in humans: relation to endocrine and clinical parameters.
AB  - OBJECTIVE: We aimed at exploring the expression of neuropeptide Y (NPY), omentin
      and visfatin in adipose tissues of adults along with clinical parameters and
      hormones. METHODS: We included 168 adult patients (31 surgical obese patients and
      31 surgical controls, 76 non-surgical obese patients, 30 non-surgical controls).
      We measured plasma NPY (by radioimmunoassay), cortisol (with an
      electrochemiluminescence immunoassay) and urinary cortisol metabolites (by gas
      chromatography/mass spectrometry). Expression of NPY, omentin and visfatin in
      subcutaneous and visceral adipose tissue specimens of the surgical patients was
      quantified using real-time PCR. RESULTS: NPY was detectable in adipose tissue
      specimens and, like plasma NPY concentrations, comparable between groups. Omentin
      gene expression was higher in visceral than in subcutaneous adipose tissues (p <
      0.0001). Visfatin expression was lower in the subcutaneous tissue of obese
      patients compared with controls (p < 0.05). Cortisol was lower in obese adults
      compared with controls (136.5 +/- 74.1 vs. 162.2 +/- 56.1 ng/ml; p < 0.05),
      cortisol metabolites were comparable between groups. CONCLUSION: In our obese
      adults, plasma NPY levels and the glucocorticoid measures were not elevated. Even
      though the expression of NPY, omentin and visfatin was comparable between obese
      individuals and controls, we have to consider differences in the total production
      rate of adipose tissue-derived factors.

PMID- 20823689
TI  - Influence of lifestyle aspects on the association of body size and shape with all
      cause mortality in middle-aged men and women.
AB  - OBJECTIVE: Waist circumference, BMI and hip circumference are differentially
      associated with mortality. We investigated the potential influence of selected
      lifestyle aspects such as smoking, alcohol intake, sports activity and education.
      METHOD: The Danish prospective study 'Diet, Cancer and Health' recruited 27,179
      men and 29,875 women from 1993 to 1997. Cox regression models were used to
      estimate mortality rate ratios. RESULTS: Adjustment for smoking habits attenuated
      the associations between mortality and the three body size measurements in both
      sexes. Adjustment for sport activity and, to a lesser extent, alcohol intake
      weakened the associations further for the men, whereas alcohol intake slightly
      weakened associations for the women. In the fully adjusted models, mortality
      increased highly significantly with higher waist circumference and lower hip
      circumference, and decreased highly significantly with higher BMI for BMI below
      25 kg/m(2). This pattern was seen for all levels of the selected lifestyle
      factor. CONCLUSION: A large waist circumference remained a strong risk indicator
      for mortality, and a large hip circumference appeared to be protective when
      smoking habits, alcohol intake and sport activity were accounted for. BMI below
      25 kg/m(2) remained a risk factor, but not above 25 kg/m(2) once waist
      circumference was adjusted for.

PMID- 20823690
TI  - A non-randomized direct comparison of cognitive-behavioral short- and long-term
      treatment for binge eating disorder.
AB  - BACKGROUND: To compare treatment outcomes of a cognitive-behavioral long-term
      (CBT-L) and short-term (CBT-S) treatment for binge eating disorder (BED) in a non
      randomized comparison and to identify moderators of treatment outcome. METHODS:
      76 female patients with BED participated in the study: 40 in CBT-L and 36 in CBT
      S. Outcome values were compared at the end of the active treatment phase (16
      sessions for CBT-L, 8 sessions for CBT-S) and at 12-month follow-up. RESULTS:
      Both treatments produced significant reductions in binge eating. At the end of
      active treatment, but not at the end of follow-up, effects of primary outcomes
      (e.g. remission from binge eating, EDE shape concern) were better for CBT-L than
      for CBT-S. Dropout rates were significantly higher in CBT-L (35%) than in CBT-S
      (14%). Moderator analyses revealed that treatment efficacy for rapid responders
      and individuals exhibiting high scores on the mixed dietary negative affect
      subtype differed between the CBT-L and CBT-S with respect to objective binges,
      restraint eating and eating concern. CONCLUSION: Findings suggest that CBT in
      general represents an effective treatment for BED, but that subgroups of patients
      might profit more from a prolonged treatment. Short, less-intensive CBT
      treatments could nevertheless be a viable option in the treatment of BED.

PMID- 20823691
TI  - Tackling the problem of overweight and obesity: the Dutch approach.
AB  - OBJECTIVE: The aim of this article is to share the Dutch experience of a nation
      wide approach to reduce the prevalence of overweight and obesity. This is an
      practice example of national health policy. METHODS: The Ministry of Health
      facilitates three complementary initiatives to tackle overweight and obesity: i)
      the Knowledge Centre Overweight (KCO) (since 2002) to enhance knowledge about
      prevention and treatment of overweight, ii) the Covenant on Overweight (CO)
      (since 2005), a public-private partnership, iii) the Partnership Overweight
      Netherlands (PON) (since 2008), to facilitate the development and implementation
      of a chronic disease management model. RESULTS: The KCO has a platform with 20
      partners that functions as a sounding board. It consists of specialists in the
      area of overweight and obesity. Moreover KCO has a well-visited website:
      www.overgewicht.org. The CO with 20 partners from the (local) government, private
      and public sector has instigated various activities regarding the settings home,
      school, work, and recreation. The PON has the commitment of 18 partners
      (organisations of health care providers, health insurance companies and patient
      organisations) and facilitates the implementation of the national clinical
      guideline for the diagnosis and treatment of obesity. CONCLUSION: In the
      Netherlands relevant stakeholders work together at all levels. The ambition is to
      make this the first integrated, practice-and evidence-based, national approach
      for tackling overweight and obesity.

PMID- 20823693
TI  - Blockade of the Renin-Angiotensin system improves insulin receptor signaling and
      insulin-stimulated skeletal muscle glucose transport in burn injury.
AB  - Burn injury is associated with a decline in glucose utilization and insulin
      sensitivity due to alterations in postreceptor insulin signaling pathways. We
      have reported that blockade of the renin-angiotensin system with losartan, an
      angiotensin II type 1 (AT1) receptor blocker, improves whole body insulin
      sensitivity and glucose metabolism after burn injury. This study examines whether
      losartan improves insulin signaling pathways and insulin-stimulated glucose
      transport in skeletal muscle in burn-injured rats. Rats were injured by a 30%
      full-skin-thickness scalding burn and treated with losartan or placebo for 3 days
      after burn. Insulin signaling pathways were investigated in rectus abdominus
      muscle taken before and 90 s after intraportal insulin injection (10 U.kg).
      Insulin-stimulated insulin receptor substrate 1-associated phosphatidylinositol 3
      kinase and plasma membrane-associated GLUT4 transporter were substantially
      increased with losartan treatment in burn-injured animals (59% above sham).
      Serine phosphorylated AKT/PKB was decreased with burn injury, and this decrease
      was attenuated with losartan treatment. In a separate group of rats, the effect
      of insulin on 2-deoxyglucose transport was significantly impaired in burned as
      compared with sham soleus muscles, in vitro; however, treatment of burned rats
      with losartan completely abolished the reduction of insulin-stimulated 2
      deoxyglucose transport. These findings demonstrate a cross talk between the AT1
      and insulin receptor that negatively modulates insulin receptor signaling and
      suggest a potential role of renin-angiotensin system blockade as a therapeutic
      strategy for enhancing insulin sensitivity in skeletal muscle and improving whole
      body glucose homeostasis in burn injury.

PMID- 20823695
TI  - Protein C concentrate as adjuvant treatment in neonates with sepsis-induced
      coagulopathy: a pilot study.
AB  - The objective of the study is to describe safety and effects of protein C
      concentrate (PCConc) administration in neonates with sepsis-induced coagulopathy.
      Eighteen neonates (12 preterm and 6 full term) aged between 1 and 28 days who
      have severe sepsis (n = 6) or septic shock (n = 12), with coagulopathy and
      acquired protein C (PC) deficiency received PCConc (i.v. bolus of 100 IU/kg,
      followed by 50 IU/kg every 6 h for 72 h). Platelet counts, prothrombin time (PT),
      activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, C-reactive
      protein (CRP), antithrombin (AT), PC, CRP, and neonatal therapeutic intervention
      scoring system (NTISS) were assessed before and 24, 48, and 72 h after the study
      entry. According to Clinical Risk Index for Babies II score (CRIB II score), the
      expected mortality in preterms was 10%. After 24 h of treatment, PC activity
      levels increased from an average of 19% to 57%, and they were within normal
      limits before the last PCConc bolus. During the treatment period, a shortening of
      PT (P = 0.04) and activated partial thromboplastin time (P = 0.02), and an
      increase in antithrombin levels (P < 0.0001) were observed, along with a
      reduction in CRP (P = 0.005) and NTISS values (P = 0.003). No adverse events were
      observed. This pilot study shows that in neonatal severe sepsis, normalization of
      PC levels is safe and probably effective in modulating the inflammatory response
      and in controlling coagulopathy. However, for the potential beneficial effects of
      PCConc administration on morbidity and mortality, a placebo-controlled, double
      blind study is required.

PMID- 20823694
TI  - The association between the transfusion of older blood and outcomes after trauma.
AB  - Allogeneic packed red blood cells (PRBCs) suppress immunity and influence
      outcomes. The influence of blood on the risk of infection and death may be
      related to the duration of storage. We sought to determine whether blood storage
      duration was associated with infection or death in a large cohort of injury
      victims. We reviewed a cohort of trauma patients transfused at least 1 U of PRBCs
      within 24 h of admission to a level 1 trauma center. The outcomes of interest
      were complicated sepsis and mortality. We compared the amount of older blood (>14
      days storage) given to patients who did or did not develop the outcomes of
      interest using univariate and multivariate methods. A total of 820 patients were
      included. Patients who died (n = 117) received more units of older blood than
      those who lived (5 U [inter quartile range {IQR}, 2-9] vs. 3 U [IQR, 2-6]; P <
      0.001). Patients with complicated sepsis (n = 244) received a greater volume of
      older blood than those without complicated sepsis (6 U [IQR, 2-10] vs. 3 U [IQR,
      1-5]; P < 0.001). After adjusting for clinical factors, including the total
      amount of blood transfused, patients receiving greater than or equal to 7 U of
      older blood had a higher risk of complicated sepsis than patients receiving 1 or
      fewer units (odds ratio, 1.9; P = 0.03). The risk for complicated sepsis and
      death in trauma victims who are transfused blood is high. The amount of older
      blood transfused is associated with complicated sepsis. Although the best
      strategy to minimize the effects of allogeneic blood is to avoid unnecessary
      transfusions, it may be particularly important to avoid transfusing multiple
      units of older blood.

PMID- 20823696
TI  - Heat stroke induces autophagy as a protection mechanism against neurodegeneration
      in the brain.
AB  - Heat stroke (HS) is defined clinically as a condition when core body temperature
      rises above 40 degrees C and is accompanied by central nervous system
      abnormalities. In this study, we established a rat model of HS by exposing
      anesthetized rats to elevated ambient temperature (40 degrees C) until core
      temperature reaching 40.5 degrees C (HS onset). The rat was immediately removed
      from heating chamber, allowed recovery for various time periods, and killed for
      histological and biochemical studies. Our results indicated neuronal shrinkage
      and pyknosis of the nucleus and sustained up to 12 h recovery time in cerebral
      cortex. Elevated expression of autophagy-related proteins, including microtubule
      associated protein light chain 3 and beclin 1 in cortical tissue at various times
      (3, 6, 12 h) of recovery was observed. In addition, the number of autophagosomes
      stained by monodansylcadaverine, a specific autophagosome marker, increased after
      heat exposure but was reduced by pretreatment with 3-methyladenine, an autophagy
      inhibitor. Furthermore, heat exposure increased neuronal degeneration in cortical
      tissue, as evidenced by staining with the fluorescent dye Fluoro-Jade B for
      degenerating neuron. Pretreatment with 3-methyladenine in HS rats aggravated
      neurodegeneration. Taken together, these results suggest that HS induces
      autophagy as a protection mechanism against neurodegeneration. Modulation of
      autophagy may provide a potential therapeutic approach for HS and await further
      research.

PMID- 20823697
TI  - Inhibition of guanylyl cyclase restores neutrophil migration and maintains
      bactericidal activity increasing survival in sepsis.
AB  - Sepsis results from an overwhelming response to infection and is a major
      contributor to death in intensive care units worldwide. In recent years, we and
      others have shown that neutrophil functionality is impaired in sepsis. This
      correlates with sepsis severity and contributes to aggravation of sepsis by
      precluding bacterial clearance. Nitric oxide (NO) is a major contributor to the
      impairment of neutrophil function in sepsis. However, attempts to inhibit NO
      synthesis in sepsis resulted in increased death despite restoring neutrophil
      migration. This could be in part attributed to a reduction of the NO-dependent
      microbicidal activity of neutrophils. In sepsis, the beneficial effects resulting
      from the inhibition of soluble guanylyl cyclase (sGC), a downstream target of NO,
      have long been appreciated but poorly understood. However, the effects of sGC
      inhibition on neutrophil function in sepsis have never been addressed. In the
      present study, we show that TLR activation in human neutrophils leads to
      decreased chemotaxis, which correlated with chemotactic receptor internalization
      and increased G protein-coupled receptor kinase 2 expression, in a process
      involving the NO-sGC-protein kinase G axis. We also demonstrate that inhibition
      of sGC activity increased survival in a murine model of sepsis, which was
      paralleled by restored neutrophil migratory function and increased bacterial
      clearance. Finally, the beneficial effect of sGC inhibition could also be
      demonstrated in mice treated after the onset of sepsis. Our results suggest that
      the beneficial effects of sGC inhibition in sepsis could be at least in part
      attributed to a recovery of neutrophil functionality.

PMID- 20823699
TI  - Treatment of infections caused by antimicrobial-resistant gram-positive bacteria.
AB  - An increasing proportion of Staphylococcus aureus infections are caused by
      methicillin-resistant S aureus. Treatment of infections caused by this organism
      is challenging, especially because therapy with vancomycin, the traditional
      antibiotic of choice for methicillin-resistant S aureus infections, is associated
      with an increasing frequency of treatment failure, and vancomycin insensitive and
      vancomycin-resistant strains have emerged. In addition, Enterococcus sp. isolated
      from human infections are increasingly resistant to multiple antimicrobial
      agents. Newer drugs available for treatment of resistant Gram-positive bacterial
      infections in the United States include linezolid, daptomycin, tigecycline and
      telavancin. The precise role for these newer agents is still evolving. Organisms
      resistant to each of these antimicrobials have emerged. New drugs in development
      include cephalosporins and carbapenems with MRSA activity.

PMID- 20823700
TI  - The dilemma of multidrug-resistant gram-negative bacteria.
AB  - Antimicrobial resistance is one of the world's most pressing public health
      problems. The worldwide use and misuse of antimicrobials in medicine and
      agriculture have resulted in the selection of bacteria resistant to the
      microbiologic activity of these agents. These resistant bacteria fail to respond
      to treatment, resulting in prolonged hospitalizations, increased cost and greater
      risk of death. This article will review the emergence of multidrug-resistant Gram
      negative bacteria, with a focus on risk factors, consequences, treatment and
      prevention for healthcare-associated infections.

PMID- 20823698
TI  - Peritoneal negative pressure therapy prevents multiple organ injury in a chronic
      porcine sepsis and ischemia/reperfusion model.
AB  - Sepsis and hemorrhage can result in injury to multiple organs and is associated
      with an extremely high rate of mortality. We hypothesized that peritoneal
      negative pressure therapy (NPT) would reduce systemic inflammation and organ
      damage. Pigs (n = 12) were anesthetized and surgically instrumented for
      hemodynamic monitoring. Through a laparotomy, the superior mesenteric artery was
      clamped for 30 min. Feces was mixed with blood to form a fecal clot that was
      placed into the peritoneum, and the abdomen was closed. All subjects were treated
      with standard isotonic fluid resuscitation, wide spectrum antibiotics, and
      mechanical ventilation, and were monitored for 48 h. Animals were separated into
      two groups 12 h (T12) after injury: for NPT (n = 6), an abdominal wound vacuum
      dressing was placed in the laparotomy, and negative pressure (-125 mmHg) was
      applied (T12 - T48), whereas passive drainage (n = 6) was identical to the NPT
      group except the abdomen was allowed to passively drain. Negative pressure
      therapy removed a significantly greater volume of ascites (860 +/- 134 mL) than
      did passive drainage (88 +/- 56 mL). Systemic inflammation (e.g. TNF-alpha, IL
      1beta, IL-6) was significantly reduced in the NPT group and was associated with
      significant improvement in intestine, lung, kidney, and liver histopathology. Our
      data suggest NPT efficacy is partially due to an attenuation of peritoneal
      inflammation by the removal of ascites. However, the exact mechanism needs
      further elucidation. The clinical implication of this study is that sepsis/trauma
      can result in an inflammatory ascites that may perpetuate organ injury; removal
      of the ascites can break the cycle and reduce organ damage.

PMID- 20823701
TI  - Infectious agents of food- and water-borne illnesses.
AB  - Food- and water-borne infections have afflicted mankind since the earliest days
      of human development and preceded the emergence of civilization. Despite current
      knowledge of microbial pathogenicity, modern methods of food production and
      rigorous industrial hygiene, these infections are still commonplace and exact
      significant health and economic tolls on human populations in all parts of the
      globe. This review uses data derived from new surveillance networks to survey the
      current epidemiology of bacterial, protozoan and viral pathogens transmitted by
      food and water. In addition, we will discuss clinical features of human disease
      caused by pathogens of current and emerging relevance.

PMID- 20823702
TI  - Opportunistic fungi: a view to the future.
AB  - Opportunistic fungi are a constantly evolving group of pathogens that plague a
      growing group of vulnerable patients. These include hospitalized patients,
      especially those in the intensive care unit; stem cell and solid organ transplant
      recipients; patients treated with immunosuppressant medications; those with
      advanced human immunodeficiency virus or other acquired immunodeficiency
      conditions; and patients with organ failure syndromes. Rapid diagnosis of
      invasive fungal infection is essential to optimize outcomes. Several newer
      nonculture-based diagnostics, including the Aspergillus galactomannan enzyme
      linked immunosorbent assay, the beta-d-glucan assay and the multiplex polymerase
      chain reaction-based assays, may emerge as important tools facilitating early
      intervention with effective antifungal therapy. Newer azoles, including
      posaconazole, isavuconazole and ravuconazole, will potentially provide more
      effective therapeutic options in the future, diminishing the role for
      amphotericin B.

PMID- 20823703
TI  - Congenital diaphragmatic hernia is a feature of Opitz G/BBB syndrome.

PMID- 20823704
TI  - Congenital diaphragmatic hernia in Lowe syndrome: a rare association?

PMID- 20823706
TI  - Foreword by Teruo Nishida.

PMID- 20823707
TI  - Transforming growth factor beta signal transduction: a potential target for
      maintenance/restoration of transparency of the cornea.
AB  - Maintenance of the transparency and regular shape of the cornea are essential to
      the normal vision, whereas opacification of the tissue impairs vision. Fibrogenic
      reaction leading to scarring in an injured cornea is characterized by appearance
      of myofibroblasts, the key player of the fibrogenic reaction, and excess
      accumulation of fibrous extracellular matrix. Inflammatory/fibrogenic growth
      factors/cytokines produced by inflammatory cells play a pivotal role in
      fibrogenic response. Signaling systems involved in myofibroblast formation and
      fibrogenesis are activated by various growth factors, i.e., transforming growth
      factor beta or others. Modulation of transforming growth factor beta signal
      transduction molecules, e.g., Smad and mitogen-activated protein kinases, by gene
      transfer and other technology provides a new concept of prevention/treatment of
      unfavorable fibrogenesis in the cornea.

PMID- 20823708
TI  - Ex vivo expansion of corneal stem cells on amniotic membrane and their outcome.
AB  - OBJECTIVES: To identify the stem-cell property of the ex vivo expansion of limbal
      stem cells (LSCs) on amniotic membrane (AM) in culture system and after clinical
      transplantation. METHODS: Four key factors have to be performed in the defined
      culture system: (1) the label-retaining cells have to be identified; (2) the
      cells can be serially expanded and passaged in vitro; (3) the expanded cells can
      be labeled by tissue-specific keratin or markers, and (3) their stem cells cannot
      be labeled by those keratin or markers. RESULTS: The ex vivo-expanded LSCs on AM
      were positive for p63 and ABCG2 and BrdU label-retaining studies on flat mount
      preparation. When the ex vivo-expanded LSCs with AM were transplanted into a
      subcutaneous layer of nude mice, they formed multiple layers of cells. Only the
      basal layer of cells was positive for p63 and BrdU. The cells over the suprabasal
      layers were positive for K12/K3. The pathologic studies of corneal specimen of
      successful LSC transplantation after penetrating keratoplasty demonstrated that
      P63-positive cells were noticed all over the basal layer of central cornea and AM
      could be identified at 10 months after LSC transplantation. CONCLUSIONS: These
      results indicate that the AM provided the niche function for cultured LSCs and
      maintained the limbal-like environment for the transplanted area of cornea. The
      survival of cases depends on the severity of the disease entity, culture
      technique, and maintenance of the niche environment for LSCs in the culture and
      after clinical transplantation.

PMID- 20823709
TI  - Corneal staining as a response to contact lens wear.
AB  - OBJECTIVE: To review the effects of contact lenses on the corneal surface.
      METHODS: A review of the literature and in-house research of corneal staining and
      its various forms of presentation. RESULTS: Corneal staining manifests in many
      different forms. The severity of staining or insult of the cornea is usually
      determined by the extent (area of coverage), density, and depth. The cause of
      staining is multifactorial, and its location is often linked to the type of lens
      that is being worn, the solution used to clean/disinfect the lens, the state of
      hydration of the soft lens, and the state of the cornea that has been affected by
      the lens. CONCLUSIONS: Sodium fluorescein dye effectively highlights corneal
      integrity changes referred to as corneal staining. This review describes the
      manifestations, the cause, the mechanisms, and the methods of remediation of
      corneal staining.

PMID- 20823710
TI  - Remodelling of the heart and vessels in experimental hypertension: advances in
      protection.
AB  - Left ventricular hypertrophy (LVH), despite its adaptive nature, increases
      cardiovascular morbidity and mortality. Novel approaches for protection against
      pathological heart remodelling are presented in this supplement. Melatonin
      diminishes myocardial fibrosis in rats exposed to continuous light and N-nitro-L
      arginine-methyl ester (L-NAME) treatment and reduces production of endothelium
      derived constricting factors in L-NAME-induced hypertension. Melatonin, because
      of its extraordinary antioxidant and scavenging properties, benefits for
      endothelium and sympatholytic action, may prove to be a useful protective drug
      against heart remodelling. In hypertension induced by relative aldosteronism, the
      correction of macro and micronutrient dyshomeostasis appears to act beneficially
      within pathological myocardial remodelling. Alterations in the signal cascade of
      pathological myocardial growth, including humoral stimuli, receptors,
      intracellular messengers or transcriptional factors, may be favourably modified
      at different levels. Inhibition of nuclear factor kappa B (NF-kappaB) potentiates
      hypertension development, enhances oxidative load, increases the cross-sectional
      area of the aorta and reduces nitric oxide (NO) synthase activity in L-NAME
      hypertension. It is suggested that NF-kappaB may play a protective rather than a
      deleterious role in the haemodynamically overloaded circulation. Compound 21, a
      recently developed peptide angiotensin II type 2 (AT2) receptor agonist, offers a
      novel approach in investigating the role of AT2 receptors in the protection of
      the hypertensive heart. A novel NO donor, L-419, with its intrinsic protection of
      NO, improves the entire NO signalling cascade and thus favourably influencing the
      response of the left ventricle to haemodynamic overload. LVH prevention or
      regression should be considered a therapeutic success only when, along with
      hypertrophied mass reduction, an improvement of the heart structure, function,
      metabolism and electrical stability is achieved.

PMID- 20823711
TI  - Continuous light and L-NAME-induced left ventricular remodelling: different
      protection with melatonin and captopril.
AB  - OBJECTIVE: Blood pressure enhancement induced by continuous light exposure
      represents an attractive but rarely investigated model of experimental
      hypertension. DESIGN AND METHODS: The aim of this study was to show whether the
      combination of continuous light (24 h/day) exposure and chronic N-nitro-L
      arginine-methyl ester (L-NAME) treatment induces remodelling of the left
      ventricle and whether captopril or melatonin can modify these potential
      alterations. Six groups of 3-month-old Wistar rats (nine per group) were treated
      for 6 weeks: control (untreated), L-NAME (40 mg/kg per day), exposed to
      continuous light, L-NAME treated and exposed to continuous light (L24), L24 rats
      treated with either captopril 100 mg/kg per day, or melatonin (10 mg/kg/24 h).
      Systolic blood pressure (SBP), relative weights of the left ventricle,
      endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE)
      expression in tissues, malondialdehyde and advanced oxidation protein product
      concentrations in the plasma and hydroxyproline levels in collagenous protein
      fractions were measured. RESULTS: The continuous light and L-NAME treatment led
      to hypertension, left ventricular hypertrophy (LVH) and fibrosis. An increase in
      SBP was completely prevented by captopril and partly by melatonin in the L24
      group. Both drugs reduced oxidative damage and attenuated enhanced expression of
      ACE in the myocardium. Neither of the drugs prevented the attenuation of eNOS
      expression in the combined hypertensive model. Only captopril reduced LVH
      development in L24, whereas captopril and melatonin reduced left ventricular
      hydroxyproline concentrations in soluble and insoluble collagen, respectively.
      The total hydroxyproline concentration was reduced only by melatonin. CONCLUSION:
      In hypertension induced by a combination of continuous light and L-NAME
      treatment, melatonin and captopril protect the heart against pathological left
      ventricular remodelling differently.

PMID- 20823712
TI  - Melatonin improves the restoration of endothelium-derived constricting factor
      signalling and inner diameter in the rat femoral artery after cessation of L-NAME
      treatment.
AB  - OBJECTIVE: Melatonin is suggested to be beneficial in several pathological
      conditions including arterial hypertension. One of the mechanisms proposed for
      its antihypertensive action is the protection against endothelial dysfunction. We
      investigated whether melatonin can accelerate the recovery from N(G)-nitro-L
      arginine-methyl ester (L-NAME)-induced hypertension after the cessation of L-NAME
      administration. METHODS: Male adult Wistar rats (n=40) were randomized into 3
      treated groups: 5-week L-NAME, 5-week L-NAME + 3-week vehicle, 5-week L-NAME + 3
      week melatonin and into 2 age-matched control groups. The blood pressure was
      measured in the carotid artery. The NO-signalling was represented by NO-synthase
      activity and expression in the aorta and NO-mediated relaxations of femoral and
      mesenteric arteries. The endothelium-derived-constricting factor (EDCF)
      signalling was represented by aortic cyclooxygenase-2 expression and femoral EDCF
      mediated contractions. Oxidative load was determined in the aorta based on
      conjugated dienes concentration and inner diameter was measured in femoral
      arteries. RESULTS: L-NAME caused hypertension, reduced NO-signalling and arterial
      diameter and increased oxidative load and EDCF-signalling. While the NO
      signalling was restored spontaneously 3 weeks after L-NAME cessation, the EDCF
      signalling, oxidative load and arterial remodeling were completely restored only
      when melatonin treatment was administered during the recovery period. The blood
      pressure regression was comparable between spontaneous and melatonin recovery.
      CONCLUSION: Although melatonin did not accelerate blood pressure reduction, it
      attenuated EDCF-contractions and oxidative load and enlarged arterial diameter.
      These effects may be beneficial for cardiovascular protection.

PMID- 20823714
TI  - Novel regulators and drug targets of cardiac hypertrophy.
AB  - Cardiac hypertrophy is classically considered as an adaptive and compensatory
      response enabling cardiomyocytes to increase their work output and thus cardiac
      function. Biomechanical stress and neurohumoral activation are the most important
      triggers of pathological hypertrophy and the transition of cardiac hypertrophy to
      heart failure. Several novel regulators and putative drug targets of cardiac
      hypertrophy have been found by using gene-modified and acquired models of cardiac
      hypertrophy. Recent studies have also revealed distinct patterns of cardiac
      substrate utilization in cardiac hypertrophy and heart failure. The use of novel
      systems biology techniques such as metabolomics may therefore in future provide
      insights into the metabolic processes and cardiovascular biology related to
      cardiac hypertrophy and also extend the ability to discover circulating
      biomarkers for cardiovascular diseases. The present review discusses current
      knowledge on molecular mechanisms of cardiac hypertrophy, with special emphasis
      on novel regulators and putative drug targets of cardiac hypertrophy such as the
      tissue renin-angiotensin-aldosterone system, calcineurin/nuclear factor of
      activated T cells pathway, phosphatidylinositol 3-kinase/growth promoting protein
      kinase B, mammalian target of rapamycin, histone deacetylases, AMPkinases,
      microRNAs and angiogenetic factors.

PMID- 20823713
TI  - Fibrosis in hypertensive heart disease: molecular pathways and cardioprotective
      strategies.
AB  - Fibrosis is a fundamental component of the adverse structural remodelling of
      myocardium found in hypertensive heart disease (HHD). A replacement fibrosis
      appears at sites of previous cardiomyocyte necrosis to preserve the structural
      integrity of the myocardium. Such scarring has adverse functional consequences.
      The extensive distribution of fibrosis involving the right and left heart
      suggests cardiomyocyte necrosis is widespread. Together, the loss of these
      contractile elements and fibrous tissue deposition in the form of stiff in-series
      and in-parallel elastic elements contribute to the progressive failure of this
      normally efficient muscular pump. Pathogenic mechanisms modulating fibrous tissue
      formation at sites of repair include auto/paracrine properties of locally
      generated angiotensin II and endothelin-1. This study focuses on the signal
      transducer-effector pathway involved in cardiomyocyte necrosis and the crucial
      pathogenic role of intracellular calcium overloading, and the subsequent
      induction of oxidative stress originating within its mitochondria that dictates
      the opening of the mitochondrial permeability transition pore. The ensuing
      osmotic destruction of these organelles is followed by necrotic cell death. It is
      now further recognized that calcium overloading of cardiac myocytes and
      mitochondria functioning as pro-oxidant is pathophysiologically counterbalanced
      by an intrinsically coupled zinc entry, which serves as an antioxidant. The
      prospect of raising intracellular zinc by adjuvant nutriceutical supplementation
      can, therefore, be preferentially exploited to uncouple this intrinsically
      coupled calcium-zinc dyshomeostasis in favour of endogenous antioxidant defences.
      Novel cardioprotective strategies may thus be at hand and deserve to be explored
      further in the overall management of patients with HHD.

PMID- 20823715
TI  - The role of nuclear factor kappa B and nitric oxide interaction in heart
      remodelling.
AB  - Hypertrophy of the myocardium is induced by haemodynamic and humoral alterations,
      which in turn stimulate the production of factors triggering protein synthesis,
      thus initiating myocardial growth. It has recently been documented that nuclear
      factor kappa B (NF-kappaB) represents a key factor that mediates both
      neurohormonal and proinflammatory signals leading finally to hypertrophic and/or
      fibrotic processes in the cardiovascular system. It was suggested that blockade
      of NF-kappaB may exert a protective effect against pathological myocardial
      growth. Recent data indicate that increased activity of NF-kappaB, besides its
      deleterious effects, leads to the increased production of nitric oxide, which as
      a result of its hypotensive and antigrowth activity exerts protection against the
      hypertrophic and proliferative processes. This ambivalent nature of NF-kappaB
      might limit the use of NF-kappaB inhibitors for therapeutic purposes and should
      evoke further studies to clarify unequivocally the nature of NF-kappaB inhibition
      in the haemodynamically overloaded circulation.

PMID- 20823716
TI  - Effect of nuclear factor kappa B inhibition on L-NAME-induced hypertension and
      cardiovascular remodelling.
AB  - OBJECTIVE: We aimed to analyze effects of nuclear factor-kappa B (NF-kappaB)
      inhibition on blood pressure (BP) regulation and cardiovascular remodelling.
      DESIGN: Adult 12-week-old male Wistar Kyoto rats (WKY) were treated with the
      nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME,
      40 mg/kg/day) for seven weeks. From the fourth week of L-NAME treatment, the NF
      kappaB inhibitor lactacystin (1 microg/kg) was applied once a week. Furthermore,
      age-matched WKY received L-NAME or lactacystin alone for 7 or 3 weeks,
      respectively. METHODS: Total NOS activity was determined in the left ventricle
      (LV) and aorta. The concentration of conjugated dienes, fibrosis, and collagen I
      and III levels were determined in the LV. The cross-sectional area (CSA) and wall
      thickness to internal diameter ratio (WT/ID) were measured in the aorta. RESULTS:
      L-NAME treatment increased BP significantly (145 +/- 2 mmHg vs. 110 +/- 1 mmHg in
      controls). The addition of lactacystin resulted in further significant increase
      in BP (161 +/- 3 mmHg). Similarly, lactacystin potentiated the increased
      conjugated dienes concentration induced by L-NAME. Whereas L-NAME alone did not
      affect NOS activity, the addition of lactacystin decreased it in both tissues
      investigated. The addition of lactacystin did not affect LV hypertrophy,
      fibrosis, and collagen I and III, already increased by L-NAME; however, it
      further amplified CSA in the aorta increased by L-NAME alone. WT/ID increased
      significantly only after the addition of lactacystin. CONCLUSION: Decreased NOS
      activity along with increased oxidative load may be responsible for decreased NO
      bio-availability and further BP increase after NF-kappaB inhibition in L-NAME
      induced hypertension. Increased CSA and WT/ID could contribute to this
      hypertensive process.

PMID- 20823717
TI  - The angiotensin AT2 receptor in left ventricular hypertrophy.
AB  - Left ventricular hypertrophy (LVH) is considered a major predictor of
      cardiovascular morbidity and mortality. While it is unanimously accepted that the
      angiotensin AT1 receptor is involved in the pathogenesis of hypertension and LVH,
      the role of the AT2 receptor in LVH is still controversial. Most studies
      addressing the involvement of the AT2 receptor in LVH have been performed in
      genetically altered, either AT2 receptor-deficient or AT2 receptor-overexpressing
      mice. Unfortunately, this experimental approach turned out to yield highly
      controversial results with an almost equal number of studies supporting
      prohypertrophic or antihypertrophic or neutral effects of the AT2 receptor in
      LVH. Interestingly, in-vivo studies in wild-type animals using the AT2 receptor
      antagonist, PD123319, are less controversial and mainly revealed antigrowth
      effects of the AT2 receptor provided the study duration was sufficiently long. In
      the future, the novel non-peptide AT2 receptor agonist, compound 21, will allow
      the effects of the AT2 receptor in LVH to be studied by direct, selective AT2
      receptor stimulation in vivo- a novel approach, which will hopefully help to
      overcome current controversies.

PMID- 20823718
TI  - Nitric oxide pathway in hypertrophied heart: new therapeutic uses of nitric oxide
      donors.
AB  - Left ventricular hypertrophy (LVH) is regarded as a complication common to a
      number of cardiovascular diseases, including hypertension, myocardial infarction
      and ischaemia associated with coronary artery disease. Initially LVH is a
      compensatory mechanism, but in the long term cardiac hypertrophy predisposes
      individuals to heart failure, myocardial infarction and sudden death. Alteration
      of the nitric oxide (NO) pathway is believed to play an important role in the
      haemodynamically overloaded heart and pathological cardiac remodelling. Although
      re-establishment of the physiological NO pathway could be considered an important
      therapeutic target, the use of conventional nitrates is limited in the clinical
      setting by the development of tissue resistance and tolerance and by the shortage
      of large-scale clinical trials unequivocally confirming the beneficial impact of
      NO donors on cardiovascular morbidity and mortality. The aim of this review is to
      present current therapeutic options for dealing with changes in the L-arginine-NO
      pathway. The most promising therapeutic approach is represented by a new neutral
      sugar organic nitrate, LA-419, the thiol group of which seems to protect NO from
      degradation, thereby increasing its bioavailability. In a model of aortic
      stenosis-induced pressure overload, LA-419 has been found to restore the complete
      NO signalling cascade and reduce left ventricular remodelling, but without
      restoring the original pressure gradient, indicating a possible direct
      antiproliferative effect. Future studies are needed to confirm this therapeutic
      benefit in other animal models of hypertension and in the clinical setting.

PMID- 20823719
TI  - Cardiac hypertrophy and remodelling: pathophysiological consequences and
      protective effects of melatonin.
AB  - This survey summarizes the limited findings related to the ability of
      endogenously produced and exogenously administered melatonin to modify the
      response of the heart musculature to pathological situations that are normally
      accompanied by hypertrophy of the cardiomyocytes and alterations in
      cardiovascular physiology. Whereas melatonin did not reduce left ventricular
      hypertrophy in spontaneously hypertensive rats or in nitric oxide-deficient
      hypertension, it did have other beneficial effects, e.g. it curtailed oxidative
      damage to the heart that resulted in an attenuation of left ventricular fibrosis.
      In contrast to the findings in hypertensive rats, melatonin administration was
      effective in overcoming cardiac enlargement resulting from induced
      hyperthyroidism or chronic hypoxia exposure. In addition, in these situations,
      melatonin also conferred protection against free radical-mediated damage at the
      level of cardiomyocytes. Collectively, the results of the publications summarized
      herein along with numerous other published reports on other aspects of
      cardiovascular physiology indicate that, when damage to the heart is a result of
      free radicals, melatonin is clearly protective. This is not unexpected
      considering the now well documented potent antioxidative actions of both
      melatonin and its metabolites. In general, melatonin improves cardiovascular
      physiology and heart function.

PMID- 20823720
TI  - The role of complex emotions in inconsistent diagnoses of schizophrenia.
AB  - In the case of large-scale epidemiological studies, there is evidence of
      substantial disagreement when lay diagnoses of schizophrenia based on structured
      interviews are compared with expert diagnoses of the same patients. Reasons for
      this level of disagreement are investigated in the current study, which made use
      of advances in text-mining techniques and associated structural representations
      of language expressions. Specifically, the current study examined whether content
      analyses of transcribed diagnostic interviews obtained from 150 persons with
      serious psychiatric disorders yielded any discernable patterns that correlated
      with diagnostic inconsistencies of schizophrenia. In summary, it was found that
      the patterning or structure of spontaneous self-reports of emotion states in the
      diagnostic interview was associated with diagnostic inconsistencies of
      schizophrenia, irrespective of confounders; i.e., age of patient, gender, or
      ethnicity. In particular, complex emotion patterns were associated with greater
      disagreement between experts and trained lay interviewers than were simpler
      patterns.

PMID- 20823722
TI  - Attachment style and defense mechanisms in parents who abuse their children.
AB  - Adult attachment style, defense mechanisms, and personal history of abuse was
      studied in a group of abusive parents. As a group, these parents made unusually
      high use of the defense of denial; this was especially true of those with a
      Fearful attachment style. However, the use of Identification was characteristic
      of those with a Preoccupied attachment style. Further, personal abuse history was
      related to adult attachment style. Those who reported having been abused as a
      child were less likely to have a Secure attachment style, and a history of
      physical or sexual abuse was associated with a Preoccupied style. In general,
      these findings support the deactivating/hyperactivating defensive theory of
      Mikulincer et al (Emotion Regulation in Couples and Families: Pathways to
      Dysfunction and Health. 2006; pp 77-99. Washington (WA): American Psychological
      Association).

PMID- 20823721
TI  - The influence of clinicians' previous trauma exposure on their assessment of
      child abuse risk.
AB  - Research has identified high levels of trauma exposure and PTSD in professionals
      responsible for assessing children at risk for abuse. An important question
      arising is the influence of stress and trauma on professional judgment. This
      study examined the association between critical incident exposure, PTSD and
      workers' judgments of child risk. Ninety-six child protection workers
      participated in 2 simulated clinical interviews and subsequently completed
      standardized risk assessment measures. Workers reported high levels of exposure
      to critical events in the workplace and high levels of traumatic stress symptoms.
      Number of prior critical events encountered was negatively associated with
      assessment of risk. Level of traumatic stress symptoms was negatively associated
      with risk on one, but not other measures of risk. It is concluded that
      standardized measures for assessing a child's risk of abuse may be influenced by
      previous exposure to critical workplace events and levels of traumatic stress in
      workers.

PMID- 20823723
TI  - Treatment delay and excessive substance use in bipolar disorder.
AB  - The aim of the present study was to investigate the relationship between
      treatment delay and excessive substance use. A total of 151 bipolar disorder (BD)
      I and II patients were consecutively recruited from in- and outpatient
      psychiatric units, and categorized as primary or secondary BD (without or with
      antecedent excessive substance use). Predictors of treatment delay among all
      patients, and predictors of subsequent excessive substance use among primary BD
      patients, were investigated with logistic regression analyses. The median
      treatment delay was 2.0 years (IQR 14.0). The risk of long treatment delays was
      increased in patients with BD II disorder, no lifetime psychosis, a higher age at
      first contact with specialized psychiatric services, primary BD, and excessive
      substance use. In primary BD, the risk for developing excessive substance use was
      increased in males, in patients with shorter education and longer treatment
      delays. Patients with antecedent excessive substance use had reduced risk of long
      treatment delays. The risk of developing excessive substance use after BD onset
      increased with longer treatment delays.

PMID- 20823724
TI  - Linguistic ability and mental health outcomes among deaf people with
      schizophrenia.
AB  - Cognition has become prominent in the study of schizophrenia because of its
      importance for understanding the etiology of the illness and its consequences for
      living independently. For people with schizophrenia who are also deaf,
      investigations of cognition and schizophrenia are infrequent. This study examines
      the role of linguistic ability in relation to cognition, social cognition, and
      functional outcome among deaf adults with schizophrenia or schizoaffective
      disorder. The primary finding is that linguistic ability is positively and
      significantly associated with functional outcome above and beyond the
      contribution of cognition and social cognition. A younger age of sign language
      acquisition is significantly associated with superior linguistic ability, but did
      not moderate the effect of linguistic ability on other domains. Opportunities for
      deaf mental health consumers to participate in sign language enrichment programs
      and communicate with other skilled signers may be useful additions to standard
      psychiatric rehabilitation programming. More research is needed to clarify the
      consequences of deafness with regards to schizophrenia especially as it relates
      to language, vision, and symptoms.

PMID- 20823725
TI  - Lifetime prevalence and correlates of suicidal ideation, plan, and single and
      multiple attempts in a Korean nationwide study.
AB  - This was the first Korean national study to evaluate prevalence and correlates of
      suicidal behavior, and to compare multiple and single attempts. A total of 6510
      adults completed face-to-face interviews (response rate, 81.7%) through randomly
      chosen one-person-per-households. Lifetime prevalence and correlates were
      evaluated with the Korean version of Composite International Diagnostic Interview
      (K-CIDI), and a questionnaire to inquire about suicidal behaviors. The lifetime
      prevalence of suicidal ideation, plan, and attempt in South Korea was 15.2%,
      3.3%, and 3.2% (single 2.1% and multiple 1.1%), respectively. Younger age was
      associated with attempts and more strongly associated with multiple attempts.
      Attempts were the most strongly associated with mood disorders, especially
      bipolar disorder, which was more strongly associated with multiple attempts. In
      conclusion, suicidal behaviors are highly prevalent in Korea, especially in young
      adults. Bipolar disorder was the most strongly associated disorder with suicide
      attempts, more with multiple attempts.

PMID- 20823726
TI  - Short-term psychodynamic psychotherapy versus treatment as usual for depressive
      and anxiety disorders: a randomized clinical trial of efficacy.
AB  - This randomized clinical trial aimed to evaluate the clinical efficacy of short
      term psychodynamic psychotherapy (STPP) in the treatment of patients suffering
      from anxiety or depressive disorders, as compared with a control case sample
      composed of patients undergoing treatment as usual (TAU). Sixty patients with
      depressive or anxiety disorders according to DSM IV-TR were randomly assigned in
      a 1:1 ratio to an intervention group (STPP) or control group for 12 months (T1).
      Primary outcome measures were the Symptom Checklist 90-Revised (SCL-90-R), the
      Inventory of Interpersonal Problems (IIP), and the Clinical Global Impression
      Improvement Scale. Intention to treat analysis revealed that patients who
      received STPP showed significantly more improvements in comparison with those who
      were in the TAU group on Clinical Global Impression Improvement Scale and IIP
      measures. This study offers evidence that STPP is an effective treatment for
      patients with anxiety or depressive disorders, and it could be more effective
      than TAU in improving interpersonal problems as measured by IIP.

PMID- 20823727
TI  - Attachment insecurity predicts eating disorder symptoms and treatment outcomes in
      a clinical sample of women.
AB  - We examined the extent to which attachment insecurity was related to eating
      disorder (ED) symptoms, and predictive of treatment outcomes. Women diagnosed
      with anorexia nervosa (AN) restricting subtype (ANR), AN binge purge subtype
      (ANB), or bulimia nervosa (BN) completed an attachment scale pretreatment, and ED
      symptom scales pretreatment (N = 243) and post-treatment (N = 157). A comparison
      sample of 126 non-ED women completed attachment scales on 1 occasion. Those with
      EDs had significantly higher attachment insecurity than non-ED. ANB was
      associated with higher attachment avoidance compared with ANR and BN, and higher
      attachment anxiety compared with BN. Higher attachment anxiety was significantly
      related to greater ED symptom severity and poorer treatment outcome across all
      EDs even after controlling for ED diagnosis. Attachment dimensions substantially
      contribute to our understanding of ED symptoms and treatment outcome. Addressing
      attachment insecurity when treating those with EDs may improve treatment
      outcomes.

PMID- 20823728
TI  - The factor structure of the Kessler-10 questionnaire in a treatment-seeking
      sample.
AB  - The Kessler-10 (K10) questionnaire was developed as a screening instrument for
      nonspecific psychological distress. Although it was validated using
      epidemiological samples, it is increasingly being used in clinical settings. We
      sought to determine whether the factor structure of the K10 as established in
      epidemiological samples, could be replicated in a sample of treatment seeking
      adults. We used confirmatory factor analysis to investigate two established
      models of the factor structure of the K10 in a sample of clinic attendees.
      Neither the single factor model of Kessler et al., Psychol Med. 2002;32:959-976,
      nor the multifactorial model of Brooks et al., Psychol Assess. 2006;18:62-70
      fitted the data. Respecification of the Kessler et al. model to reduce item
      redundancy did not result in adequate fit. These findings call into question the
      construct validity of the K10 in treatment seeking samples, and the suitability
      of the scale for clinical settings may need to be reconsidered.

PMID- 20823729
TI  - Attrition in a multicenter clinical trial for panic disorder.
AB  - This study examined attrition in a multisite clinical trial for panic disorder.
      Of 379 eligible patients, 19 refused treatment (5% Refusal Rate), 104
      discontinued treatment prematurely (19% Dropout Rate) or were withdrawn by the
      investigators (8% Withdrawal Rate), and 256 completed the treatment (68%
      Completion Rate). Logistic regression was used to examine 5 domains theorized to
      be related to attrition (e.g., diagnostic severity, treatment factors). Few
      variables were associated with increased odds of attrition at padj < 0.004.
      Younger age was the only independent predictor of attrition in the demographic
      factor model. Diagnostic severity and comorbidity, panic disorder symptom
      severity, treatment factors, and therapist factors were unrelated to study
      attrition. Patient dropout was highest after treatment sessions that targeted
      interoceptive and situational exposure exercises. Findings suggest that attrition
      may not strongly threaten the validity of results from treatment outcome studies.

PMID- 20823731
TI  - Clinical predictors associated with duration of repetitive transcranial magnetic
      stimulation treatment for remission in bipolar depression: a naturalistic study.
AB  - Repetitive transcranial magnetic stimulation (rTMS) has been widely tested and
      shown to be effective for unipolar depression. Although it has also been
      investigated for bipolar depression (BD), there are only few rTMS studies with
      BD. Here, we investigated 56 patients with BD who received rTMS treatment until
      remission (defined as Hamilton Depression Rating Scores < or =7). We used simple
      and multiple logistic regressions to identify clinical and demographic predictors
      associated with duration of treatment (defined as <15 vs. >15 rTMS sessions).
      Age, refractoriness, number of prior depressive episodes, and severe depression
      at baseline were associated with a longer rTMS treatment. In the multivariate
      analysis, refractoriness (likelihood ratio (LR) = 4.33; p < 0.01) and baseline
      severity (LR = 0.18, p < 0.01) remained significant predictors. Our preliminary
      study showed that, in remitted patients, refractoriness and severity of index
      episode are associated with the need of a longer rTMS treatment; providing
      preliminary evidence of important factors associated with rTMS parameters
      adjustment.

PMID- 20823730
TI  - Prenatal exposure to maternal and paternal smoking on attention deficit
      hyperactivity disorders symptoms and diagnosis in offspring.
AB  - The study examined the effect of maternal and paternal smoking during pregnancy
      on the child's inattention and hyperactivity/impulsivity symptoms, and the risk
      for attention deficit hyperactivity disorder (ADHD) and oppositional defiant
      disorder (ODD). Generalized estimating equations, incorporating data from
      multiple informants (parents and teachers), was used to evaluate levels of ADHD
      as a function of parental smoking. The risk for ADHD, ODD, and comorbid ADHD and
      ODD was evaluated using polytomous logistic regression. We found that maternal,
      but not paternal, smoking was significantly associated with elevated inattention,
      hyperactivity/impulsivity, and total ADHD symptoms in children. Children of
      smoking, relative to nonsmoking, mothers had a significant increased risk for
      comorbid ADHD and ODD and ADHD, but not ODD. Although father's smoking was not
      associated with an increased risk, as it strongly influenced mothers' smoking,
      intervention for both parents may be most effective in preventing the pathway to
      ADHD-related problems in the children.

PMID- 20823732
TI  - Prevalence of diagnosed HIV disease among medicaid beneficiaries with
      schizophrenia in U.S. metropolitan areas.
AB  - Numerous reports suggest HIV may be elevated among those with severe mental
      illnesses such as schizophrenia or bipolar illness, but this has been studied in
      only a limited number of sites. Medicaid claim's files from 2002 to 2003 were
      examined for metropolitan statistical areas (MSAs) in 8 states, focusing on
      schizophrenia. Across 102 MSAs, 1.81% of beneficiaries with schizophrenia had
      received diagnoses of HIV/AIDS. MSA rates ranged widely, from 5.2% in Newark, NJ,
      to no cases in 16 of the MSAs.

PMID- 20823733
TI  - The role of depression in the differential effect of childhood parental divorce
      on male and female adult offspring suicide attempt risk.
AB  - In previous studies by our group, we found that female offspring of parental
      divorce and parental remarriage are more susceptible to suicide attempt than male
      offspring. In this study, we examine whether these findings remain even after
      controlling for offspring depression. The sample consists of respondents from the
      2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions.
      Multivariable regressions controlled for offspring depression, parental
      depression, age, race/ethnicity, income, and marital status. Our previous
      findings that female offspring of parental divorce and parental remarriage are
      more likely to report a lifetime suicide attempt than male offspring remained
      even after controlling for offspring depression. Findings suggest that focusing
      on engaging female offspring who demonstrate symptoms of depression is not
      sufficient to reduce suicide attempt risk in this group as many at risk
      individuals will remain unrecognized.

PMID- 20823734
TI  - Negative emotional valence is associated with non-right-handedness and increased
      imbalance of hemispheric activation as measured by tympanic membrane temperature.
AB  - We investigated the possibility that individual differences in hand preference
      influence hemispheric emotional valence asymmetries using the Profile of Mood
      States Short-Form (Shacham, J Pers Assess. 1983;47:305-306) as a measure of
      emotional valence and tympanic membrane temperature (TMT) as a measure of
      hemispheric activity. We replicate others' findings of increased negative valence
      in the non-right-handed. We further demonstrate handedness effects on the
      absolute difference between left and right TMT, and a positive relationship
      between this measure and the anger/hostility subscale of the Profile of Mood
      States Short Form. Findings suggest (i) negative emotional valence is associated
      with extreme asymmetries of cortical activation and (ii) TMT may be a simple
      means by which emotional state may be indicated, with increased difference
      between left and right TMT, suggesting increased anger/hostility. These findings
      offer the possibility of an exceptionally simple measure that may, in conjunction
      with more established techniques, offer valuable diagnostic information,
      particularly for disorders involving anger/hostility.

PMID- 20823736
TI  - Mortality, morbidity, and pediatric critical care.

PMID- 20823737
TI  - Pathophysiology of disinhibition of complement activation.

PMID- 20823738
TI  - Pulling the triggers on adverse events in the pediatric intensive care unit.

PMID- 20823739
TI  - Dexmedetomidine and pulmonary artery pressure in the pediatric cardiac surgery
      patient--A new insight.

PMID- 20823740
TI  - Intracranial pressure: A role for a surrogate measurement?

PMID- 20823741
TI  - Impact of influenza A/pH1N1 2009 in Canada and elsewhere.

PMID- 20823742
TI  - Is electric impedance tomography the white knight for acute respiratory distress
      syndrome?

PMID- 20823743
TI  - A call for full public disclosure and moratorium on donation after cardiac death
      in children.

PMID- 20823746
TI  - Dexmedetomidine as a postoperative sedative after congenital cardiac surgery-
      Consideration of the anesthetic management has an important role.

PMID- 20823748
TI  - Management of asymptomatic ovarian and other adnexal cysts imaged at US Society
      of Radiologists in Ultrasound consensus conference statement.
AB  - The Society of Radiologists in Ultrasound (SRU) convened a panel of specialists
      from gynecology, radiology, and pathology to arrive at a consensus regarding the
      management of ovarian and other adnexal cysts imaged sonographically in
      asymptomatic women. The panel met in Chicago, IL, on October 27-28, 2009, and
      drafted this consensus statement. The recommendations in this statement are based
      on analysis of current literature and common practice strategies, and are thought
      to represent a reasonable approach to asymptomatic ovarian and other adnexal
      cysts imaged at ultrasonography.

PMID- 20823749
TI  - Takayasu arteritis.

PMID- 20823750
TI  - Dynamic ultrasound of hernias of the groin and anterior abdominal wall.

PMID- 20823751
TI  - Pearls and pitfalls of thyroid nodule sonography and fine-needle aspiration.
AB  - PURPOSE: To review the ultrasound appearances of thyroid nodules with an emphasis
      on morphological features and to illustrate pearls and pitfalls related to
      ultrasound interpretation and fine-needle aspiration. METHODS: The ultrasound
      features of 156 consecutive thyroid nodules with available cytological diagnoses
      were retrospectively reviewed. The presence of "honeycomb" morphology, aspect
      ratio, taller-than-wide shape, presence of colloid, consistency, echogenicity,
      presence of halo, margin definition, multiplicity of the nodules, largest nodule
      dimension, and lesion vascularity were compared between benign and malignant
      nodules. RESULTS: Sonographic features that are significantly more common among
      malignant lesions include the presence of microcalcifications, coarse internal
      calcifications, markedly hypoechoic components, mostly solid-to-solid contents,
      infiltrative or microlobulated margins, taller-than-wide shape, and a high aspect
      ratio (0.85 vs 0.71). Characteristics that are statistically significantly
      associated with benignity include peripheral calcification and purely cystic
      composition. The honeycomb morphology was 100% specific for nodular hyperplasia.
      Benign and malignant follicular and Hurthle cell neoplasms can have identical
      sonographic and cytological features. Colloid on both ultrasound and cytology may
      be found in malignant lesions, whereas microcalcifications can sometimes be found
      in benign lesions. Cystic components in malignant nodules are not uncommon and
      should not be dismissed as benign on this basis alone. Fine-needle aspiration may
      alter the appearance of thyroid nodules. CONCLUSIONS: Certain morphological
      sonographic features are helpful for differentiating between benign and malignant
      thyroid nodules and guided subsequent management. However, thyroid nodule
      ultrasound and fine-needle aspiration must be interpreted with awareness of
      potential pitfalls.

PMID- 20823752
TI  - Ultrasound-guided percutaneous biopsy of the augmented breast using implant
      displacement: a new technique.
AB  - The purpose of the technique was to develop a method of performing ultrasound
      guided percutaneous biopsy of the augmented breast that would reduce risk of
      causing implant rupture. Using adhesive tape, we have displaced retropectoral
      implants away from the lesion to be biopsied. This resulted in greater space
      between the lesion and the implant and allowed ultrasound-guided biopsy to be
      accomplished with greater ease and with reduced risk of rupturing the implant.

PMID- 20823756
TI  - Sitting posture decreases collapsibility of the passive pharynx in anesthetized
      paralyzed patients with obstructive sleep apnea.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is an independent risk factor for
      difficult and/or impossible mask ventilation during anesthesia induction.
      Postural change from supine to sitting improves nocturnal breathing in patients
      with OSA. The purpose of this study was to evaluate the effect of patient
      position on collapsibility of the pharyngeal airway in anesthetized and paralyzed
      patients with OSA. The authors tested the hypothesis that the passive pharynx is
      structurally less collapsible during sitting than during supine posture. METHOD:
      Total muscle paralysis was induced with general anesthesia in nine patients with
      OSA, eliminating neuromuscular factors contributing to pharyngeal patency. The
      cross-sectional area of the pharynx was measured endoscopically at different
      static airway pressures. Comparison of static pressure-area plots between the
      supine and sitting (62 degrees  head-up) allowed assessment of the postural
      differences of the mechanical properties of the pharynx. RESULTS: : Maximum cross
      sectional area was greater during sitting than during supine posture at both
      retropalatal (median (10th-90th percentile): 1.91 (1.52-3.40) versus 1.25 (0.65
      1.97) cm) and retroglossal (2.42 (1.72-3.84) versus 1.75 (0.47-2.35) cm) airways.
      Closing pressure of the passive pharynx was significantly lower during sitting
      than supine posture. Differences of the closing pressures between the postures
      are 5.89 (3.73-11.6) and 6.74 (4.16-9.87) cm H2O, at retropalatal and
      retroglossal airways, respectively, and did not differ between the pharyngeal
      segments. CONCLUSIONS: Postural change from supine to sitting significantly
      improves collapsibility of pharyngeal airway in anesthetized and paralyzed
      patients with OSA.

PMID- 20823758
TI  - The American Society of Anesthesiologists closed claims project: the beginning.

PMID- 20823757
TI  - Isoflurane preconditioning elicits competent endogenous mechanisms of protection
      from oxidative stress in cardiomyocytes derived from human embryonic stem cells.
AB  - BACKGROUND: Human embryonic stem cell (hESC)-derived cardiomyocytes potentially
      represent a powerful experimental model complementary to myocardium obtained from
      patients that is relatively inaccessible for research purposes. We tested whether
      anesthetic-induced preconditioning (APC) with isoflurane elicits competent
      protective mechanisms in hESC-derived cardiomyocytes against oxidative stress to
      be used as a model of human cardiomyocytes for studying preconditioning. METHODS:
      H1 hESC cell line was differentiated into cardiomyocytes using growth factors
      activin A and bone morphogenetic protein-4. Living ventricular hESC-derived
      cardiomyocytes were identified using a lentiviral vector expressing a reporter
      gene (enhanced green fluorescent protein) driven by a cardiac-specific human
      myosin light chain-2v promoter. Mitochondrial membrane potential, reactive oxygen
      species production, opening of mitochondrial permeability transition pore, and
      survival of hESC-derived cardiomyocytes were assessed using confocal microscopy.
      Oxygen consumption was measured in contracting cell clusters. RESULTS:
      Differentiation yielded a high percentage (~85%) of cardiomyocytes in beating
      clusters that were positive for cardiac-specific markers and exhibited action
      potentials resembling those of mature cardiomyocytes. Isoflurane depolarized
      mitochondria, attenuated oxygen consumption, and stimulated generation of
      reactive oxygen species. APC protected these cells from oxidative stress-induced
      death and delayed mitochondrial permeability transition pore opening.
      CONCLUSIONS: APC elicits competent protective mechanisms against oxidative stress
      in hESC-derived cardiomyocytes, suggesting the feasibility to use these cells as
      a model of human cardiomyocytes for studying APC and potentially other
      treatments/diseases. Our differentiation protocol is very efficient and yields a
      high percentage of cardiomyocytes. These results also suggest a promising ability
      of APC to protect and improve engraftment of hESC-derived cardiomyocytes into the
      ischemic heart.

PMID- 20823760
TI  - Neurally adjusted ventilatory assist in critically ill postoperative patients: a
      crossover randomized study.
AB  - BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is a new mode of
      mechanical ventilation that delivers ventilatory assist in proportion to the
      electrical activity of the diaphragm. This study aimed to compare the ventilatory
      and gas exchange effects between NAVA and pressure support ventilation (PSV)
      during the weaning phase of critically ill patients who required mechanical
      ventilation subsequent to surgery. METHODS: Fifteen patients, the majority of
      whom underwent abdominal surgery, were enrolled. They were ventilated with PSV
      and NAVA for 24 h each in a randomized crossover order. The ventilatory
      parameters and gas exchange effects produced by the two ventilation modes were
      compared. The variability of the ventilatory parameters was also evaluated by the
      coefficient of variation (SD to mean ratio). RESULTS: Two patients failed to
      shift to NAVA because of postoperative bilateral diaphragmatic paralysis, and one
      patient interrupted the study because of worsening of his sickness. In the other
      12 cases, the 48 h of the study protocol were completed, using both ventilation
      modes, with no signs of intolerance or complications. The Pao2/Fio2 (mean +/- SD)
      ratio in NAVA was significantly higher than with PSV (264 +/- 71 vs. 230 +/- 75
      mmHg, P < 0.05). Paco2 did not differ significantly between the two modes. The
      tidal volume (median [interquartile range]) with NAVA was significantly lower
      than with PSV (7.0 [6.4-8.6] vs. 6.5 [6.3-7.4] ml/kg predicted body weight, P <
      0.05).Variability of insufflation airway pressure, tidal volume, and minute
      ventilation were significantly higher with NAVA than with PSV. Electrical
      activity of the diaphragm variability was significantly lower with NAVA than with
      PSV. CONCLUSIONS: Compared with PSV, respiratory parameter variability was
      greater with NAVA, probably leading in part to the significant improvement in
      patient oxygenation.

PMID- 20823759
TI  - Caspase-1 modulates incisional sensitization and inflammation.
AB  - BACKGROUND: Surgical injury induces production and release of inflammatory
      mediators in the vicinity of the wound. They in turn trigger nociceptive
      signaling to produce hyperalgesia and pain. Interleukin-1beta plays a crucial
      role in this process. The mechanism regulating production of this cytokine after
      incision is, however, unknown. Caspase-1 is a key enzyme that cleaves
      prointerleukin-1beta to its active form. We hypothesized that caspase-1 is a
      crucial regulator of incisional interleukin-1beta levels, nociceptive
      sensitization, and inflammation. METHODS: These studies employed a mouse hind paw
      incisional model. Caspase-1 was blocked using the selective inhibitors Ac-YVAD
      CMK and VRTXSD727. Nociceptive sensitization, edema, and hind paw warmth were
      followed in intact animals whereas caspase-1 activity, cytokine, and
      prostaglandin E2 levels were assessed in homogenized skin. Confocal microscopy
      was used to detect the expression of caspase-1 near the wounds. RESULTS: Analysis
      of enzyme activity demonstrated that caspase-1 activity was significantly
      increased in periincisional skin. Pretreatment with Ac-YVAD-CMK significantly
      reduced mechanical allodynia and thermal hyperalgesia. Repeated administration of
      this inhibitor produced robust analgesia, especially to mechanical stimulation.
      Administration of VRTXSD727 provided qualitatively similar results. Caspase-1
      inhibition also reduced edema and the normally observed increase in paw warmth
      around the wound site. Correspondingly, caspase-1 inhibition significantly
      reduced interleukin-1beta as well as macrophage-inflammatory protein 1alpha,
      granulocyte colony-stimulating factor, and prostaglandin E2 levels near the
      wound. The expression of caspase-1 was primarily observed in keratinocytes in the
      epidermal layer and in neutrophils deeper in the wounds. CONCLUSIONS: The current
      study demonstrates that the inhibition of caspase-1 reduces postsurgical
      sensitization and inflammation, likely through a caspase-1/interleukin-1beta
      dependent mechanism.

PMID- 20823761
TI  - Lymphocyte-based determination of susceptibility to malignant hyperthermia: a
      pilot study in swine.
AB  - BACKGROUND: Malignant hyperthermia susceptibility (MHS) is diagnosed by an
      invasive in vitro caffeine-halothane contracture test (CHCT) carried out on
      biopsied skeletal muscle tissue. We are presenting a novel blood test approach
      for malignant hyperthermia testing in a swine model. Our main aim was to
      determine whether adenosine production from lymphocytes after 4-chloro-m-cresol
      (4CmC) stimulation distinguishes homozygous swine carrying the Arg615Cys mutation
      in the ryanodine receptor type 1 (RyR1) gene (MHS swine) from normal swine.
      METHODS: Lymphocytes were isolated from arterial blood (40 ml) obtained from MHS
      (n = 7) and normal (n = 7) swine. Cells were suspended in Hank's balanced salt
      solution and treated with 4CmC (0-10 mm) at 37 degrees C in the presence of
      adenosine deaminase inhibitor. After termination and purification of samples,
      aliquots (50 MUl) were assayed for adenosine content using high performance
      liquid chromatography. RESULTS: Baseline adenosine levels before stimulating
      lymphocytes with 4CmC were 0.025 +/- 0.004 and 0.041 +/- 0.006 MUm (mean +/- SEM)
      in lymphocytes from normal and MHS swine, respectively (P = 0.125). Maximum
      responses were achieved at 1 mm 4CmC for both cell-line groups. Adenosine levels
      after stimulation with 4CmC (1 mm) were 0.185 +/- 0.009 and 0.397 +/- 0.038 MUm
      in lymphocytes from normal and MHS swine, respectively (P = 0.0035). There was no
      overlap between adenosine levels in stimulated lymphocytes from MHS and normal
      swine. CONCLUSION: 4CmC stimulation of porcine lymphocytes induces increased
      adenosine formation in MHS cells relative to those from normal swine; evaluation
      of adenosine formation in response to RyR1 agonists in human lymphocytes is
      needed.

PMID- 20823762
TI  - Effect of stellate ganglion block on the cerebrovascular system: magnetic
      resonance angiography study.
AB  - BACKGROUND: Several studies have shown that stellate ganglion block (SGB) is an
      effective treatment for certain cerebrovascular related diseases; however, the
      direct effect of SGB on the cerebral vasculature is still unknown. The present
      study investigated the effect of SGB on the cerebral vascular system using
      magnetic resonance angiography. METHODS: Time-of-flight magnetic resonance
      angiography images of 19 healthy female volunteers (mean ages of 46.4 +/- 8.9 yr)
      were obtained before and after SGB with 1.5-T magnetic resonance imaging. The
      authors determined successful interruption of sympathetic innervation to the head
      with the appearance of Horner syndrome and conjunctival injection. We measured
      changes in the average signal intensity and diameter of the major intracranial
      and extracranial arteries and their branches, which were presented with mean (+/
      SE). RESULTS: The signal intensity changes were observed mainly in the
      ipsilateral extracranial vessels; the external carotid artery (11.2%, P < 0.001)
      and its downstream branches, such as the occipital artery (9.5%, P < 0.001) and
      superficial temporal artery (14.1%, P < 0.001). In contrast, the intensities of
      the intracranial arteries did not change with the exception of the ipsilateral
      ophthalmic artery, which increased significantly (10.0%, P = 0.008). After SGB,
      only the diameter of the ipsilateral external carotid artery was significantly
      increased (26.5%, P < 0.001). CONCLUSIONS: We were able to observe significant
      changes in the extracranial vessels, whereas the intracranial vessels were
      relatively unaffected (except for the ophthalmic artery), demonstrating that both
      perivascular nerve control and sympathetic nerve control mechanisms may
      contribute to the control of intracranial and extracranial blood vessels,
      respectively, after SGB.

PMID- 20823763
TI  - Efficacy and safety of melatonin as an anxiolytic and analgesic in the
      perioperative period: a qualitative systematic review of randomized trials.
AB  - Melatonin possesses sedative, hypnotic, analgesic, antiinflammatory,
      antioxidative, and chronobiotic properties that distinguish it as an attractive
      alternative premedicant. A qualitative systematic review of the literature
      concerning the perioperative use of melatonin as an anxiolytic or analgesic in
      adult patients was carried out using the recommended guidelines provided by the
      Cochrane Handbook for Systematic Reviews of Interventions. Nine of the 10 studies
      showed statistically significant reduction of preoperative anxiety with melatonin
      premedication compared with placebo. An opioid-sparing effect or reduced pain
      scores were evident in five studies whereas three studies were contradictory.
      Thus, melatonin premedication is effective in ameliorating preoperative anxiety
      in adults, but its analgesic effects remain controversial in the perioperative
      period. Additional well designed randomized controlled trials are necessary to
      compare melatonin premedication with other pharmacological interventions,
      investigate its effect on more varied surgical populations, and to delineate its
      optimal dosing regimen.

PMID- 20823764
TI  - Images in anesthesiology: thyroid cancer invading the trachea.

PMID- 20823765
TI  - Laryngoscopy complicated by thyroid cartilage fracture.

PMID- 20823766
TI  - Can we tell the site of origin of metastatic squamous cell carcinoma? An
      immunohistochemical tissue microarray study of 194 cases.
AB  - To the workup of metastatic squamous cell carcinoma (SCC) of unknown primary, we
      studied an immunohistochemical panel including thyroid transcription factor (TTF
      1), napsin A, villin, CDX-2, K903, CK5/6, p63, p16, CK7, and CK20. Using tissue
      microarray, we compared 194 SCC cases from the following sites: 35 lung, 34 skin,
      14 cervix, 4 vagina, 16 vulva, 8 penis, 9 anus, 3 rectum, 10 esophagus, 4
      bladder/urethra, and 57 SCC from various head and neck sites. p63 and K903
      stained positively in 100% of cases, and CK5/6 in nearly 100% of cases, with the
      exception of 1 lung. CK7 was positive in 31.6% of all cases, with varying
      positivity according to the site. CK20 was negative in all cases except 1 lung.
      Napsin A was positive in 25.8% of lung, 7.7% of skin, 37.5% of penis, and 13.3%
      of tongue, and negative in all other sites. TTF-1 was positive only in 1 lung.
      p16 positivity ranged from 21.43% in vulva, to 75% in vagina and anus, and it was
      negative in lung, penis, bladder/urethra, and some head and neck. CDX-2 was
      negative in all cases except 1 vulva. Villin was negative in all cases. We
      conclude that immunohistochemistry has very limited value in determining the
      primary site of metastatic SCC. If lung is in the differential versus head and
      neck, esophagus, anorectal, or genital SCC, a panel including TTF-1, napsin A and
      p16 may be helpful, since positive TTF-1 and/or napsin A would favor lung
      primary, and positive p16 would favor an extrapulmonary site.

PMID- 20823767
TI  - Thymoma with nuclear expression of thyroid transcription factor-1: a potential
      diagnostic pitfall on core biopsy.
AB  - The clinicopathologic features of the first case of a thymoma with a strong
      nuclear expression of thyroid transcription factor-1 are reported. The thymoma
      was classified as type AB according to the WHO-system. No definitive correlation
      between the different histologic patterns or neoplastic cell types and thyroid
      transcription factor-1 expression was discerned. No immunohistochemical evidence
      of neuroendocrine differentiation was identified with synaptophysin, chromogranin
      A, and CD56.

PMID- 20823768
TI  - C-KIT and PDGFRA zygosity in gastrointestinal stromal tumors: Correlation with
      tumor site, tumor size, exon, and CD117 immunohistochemistry.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GISTs) often harbor activating
      mutations in the receptor tyrosine kinases C-KIT or platelet derived growth
      factor receptor-alpha (PDGFRA). Gain-of-function mutations in these 2 genes,
      which result in constitutive signaling, are presumed to be dominant and therefore
      are usually heterozygous. However, homozygous C-KIT mutations have been reported
      in GISTs, although at varying frequencies in different subsets. METHODS: High
      resolution amplicon melting curve analysis and direct sequencing were used to
      determine the frequency of mutation zygosity in a series of 267 GIST cases with
      known C-KIT (exons 9, 11, 13 and 17) or PDGFRA (exons 12 and 18) mutations.
      Mutation zygosity was correlated with clinicopathological characteristics
      including sex, age, tumor size, tumor location, and C-KIT immunohistochemistry.
      RESULTS: Forty-two of 267 (15.7%) mutant GISTs were homozygous: 36 in C-KIT exon
      11, 1 in C-KIT exon 13, 2 in PDGFRA exon 12, and 3 in PDGFRA exon 18. No
      correlation was found between mutation zygosity and age, sex, tumor size, or C
      KIT expression. Homozygous mutant GISTs from the small intestine were
      underrepresented (P=0.029) whereas GISTs from metastatic sites such as the liver
      or pancreas were significantly enriched for mutant homozygosity (P=0.020).
      CONCLUSIONS: Zygosity of C-KIT or PDGFRA mutations did not correlate with most
      clinicopathologic features of GISTs including tumor size in our subset. However,
      homozygous mutant GISTs were associated with metastatic disease.

PMID- 20823769
TI  - Immunohistochemistry on epoxy resin-embedded bone marrow biopsy experience with
      936 cases.
AB  - The investigators adapted a method to process 150 bone marrow trephine biopsies
      per year at a general hospital providing pathological diagnosis for a subcenter
      hematological ward. In brief, specimens were fixed in 10% formaldehyde and
      embedded in epoxy resin at 56 degrees C without decalcification. The resin was
      extracted with sodium-etoxide from the sections. Following rehydration,
      immunohistochemistry was carried out similar to the paraffin method with the
      usual antigen retrieval and Envision-DAB development. High resolution
      cytomorphology and immunomorphology was possible without semithin technique. The
      turnaround time was 3 days: 1 day each for fixation, for resin
      infiltration/polymerization and for cutting/staining. The antibody panel included
      40 to 50 primary antibodies. The final diagnoses were aided by smear morphology,
      flow cytometry, and lymphoid organ pathology, as required by the special
      circumstances of the cases.

PMID- 20823770
TI  - Correlation of immunohistochemical expression of p53 with unamplified chromosome
      17 polysomy in invasive breast carcinoma.
AB  - p53 functions as a tumor suppressor gene and is frequently mutated and
      inactivated in several human cancers. Some studies have shown p53 overexpression
      in breast cancer to be an independent prognostic indicator. A subset of breast
      cancers have chromosome 17 polysomy. Although p53 immunostaining has been found
      to correlate with chromosome 17 polysomy in nonsmall cell lung carcinomas, head
      and neck squamous cell carcinomas, and bladder carcinomas, its expression has not
      been correlated with chromosome 17 polysomy in breast carcinomas. In this study,
      we compared p53 expression by immunohistochemistry in cases of invasive breast
      carcinoma showing unamplified chromosome 17 polysomy (P) with cases showing HER2
      amplification (A) and with those showing neither amplification nor polysomy (N).
      There was a significant overexpression of p53 in both cases with HER2
      amplification and unamplified polysomy 17 compared with cases with neither
      amplification nor polysomy (7% of N, 25% of P, and 37% of A group were p53
      positive). We have shown in an earlier study that invasive breast carcinoma with
      unamplified chromosome 17 polysomy is associated with several adverse prognostic
      indicators including a higher Nottingham score and greater estrogen receptor (ER)
      negativity with a trend toward the amplified group, in contrast to patients with
      neither amplification nor polysomy. In this study, we now show that p53
      positivity in unamplified 17 polysomy identifies cases that are associated with
      an even higher Nottingham score and greater hormone receptor negativity that is
      similar to cases with HER2 amplification.

PMID- 20823771
TI  - Response topography in behavioral tolerance to cocaine with rats.
AB  - Research conducted with rats has shown tolerance to the behavioral effects of
      psychomotor stimulants to be contingent on chronic drug administration occurring
      before the experimental session. Recent experiments with pigeons, however,
      resulted in tolerance when drug administration followed the experimental session.
      We hypothesized that the apparent species differences in tolerance may be a
      function of different operantly conditioned response topographies used in these
      experiments. Specifically, we propose that operantly reinforced consummatory
      responses, like pecking with pigeons, are less likely to reveal contingent
      tolerance. This experiment involved rats in a manner that paralleled earlier
      experiments with pigeons. Rats were subjected to daily sessions that required 20
      licking responses to obtain 2.5-s access to water. Acute effects of cocaine were
      determined by administering precession doses ranging from 1.0 to 30.0 mg/kg, with
      dosing occurring every fifth day. Rats were then divided into two groups. One
      group received 17.0 mg/kg cocaine before the session and the other received 17.0
      mg/kg cocaine after the session. After 30 daily sessions, the effects of the
      cocaine-dose range were reassessed. Tolerance to the rate-decreasing effects of
      cocaine was evident in both the groups, regardless of the temporal relationship
      between drug administration and the experimental session. The results support the
      hypothesis that operantly reinforced consummatory responses are less likely to
      show contingent tolerance.

PMID- 20823772
TI  - Resveratrol: a relevant pharmacological approach for the treatment of metabolic
      syndrome?
AB  - PURPOSE OF REVIEW: The metabolic syndrome is associated with increased risk for
      development of both cardiovascular disease and type 2 diabetes in humans. Because
      experimental data and clinical experience have shown that metabolic syndrome and
      caloric restriction have, at least partly, opposite pathophysiological pathways,
      the activation of sirtuins may constitute a pharmacological approach to treat
      metabolic syndrome. Resveratrol is a polyphenol produced by plants that has
      multiple beneficial activities similar to those associated with caloric
      restriction. RECENT FINDINGS: Through its regulatory action of both AMP kinase
      and the sirtuin sirtuin-1, resveratrol is a natural sirtuin activator that
      certainly will be the head of a new pharmacological family of drugs targeted on
      sirtuin-1 activity exacerbation in order to treat/protect from obesity and
      diabetes, and thus metabolic syndrome. SUMMARY: This review discusses the
      therapeutic use of resveratrol and sirtuin activators in the context of insulin
      resistance and obesity, the two main features of metabolic syndrome.

PMID- 20823773
TI  - Butyrate and other short-chain fatty acids as modulators of immunity: what
      relevance for health?
AB  - PURPOSE OF REVIEW: High-fiber diets have been shown to reduce plasma
      concentrations of inflammation markers. Increased production of fermentation
      derived short-chain fatty acids (SCFAs) is one of the factors that could exert
      these positive effects. This review examines the effects of SCFAs on immune cells
      and discusses the relevance of their effects on systemic inflammation, as
      frequently seen in obesity. RECENT FINDINGS: SCFAs have been shown to reduce
      chemotaxis and cell adhesion; this effect is dependent on type and concentration
      of SCFA. In spite of conflicting results, especially butyrate seems to have an
      anti-inflammatory effect, mediated by signaling pathways like nuclear factor
      kappaB and inhibition of histone deacetylase. The discrepancies in the results
      could be explained by differences in cell types used and their proliferative and
      differentiation status. SUMMARY: SCFAs show anti-inflammatory effects and seem to
      have the potency to prevent infiltration of immune cells from the bloodstream in,
      for example, the adipose tissue. In addition, their ability to inhibit the
      proliferation and activation of T cells and to prevent adhesion of antigen
      presenting cells could be important as it recently has been shown that obesity
      associated inflammation might be antigen-dependent. More studies with
      concentrations in micromolar range are needed to approach more physiological
      concentrations.

PMID- 20823774
TI  - Hair loss in long-term or home parenteral nutrition: are micronutrient
      deficiencies to blame?
AB  - PURPOSE OF REVIEW: To review the key nutritional factors associated with hair
      loss in long-term parenteral nutrition patients. RECENT FINDINGS: The phenomenon
      of unexplained hair loss is multifactorial, and nonstandard definitions are
      applied. Deficiencies of essential fatty acids resulting in alopecia and other
      symptoms appear to have been eliminated by regular use of lipid-containing
      parenteral nutrition. Zinc is the most frequently suspected deficiency with rapid
      clinical responses reported from zinc therapy. Alopecia in some infants on
      parenteral nutrition has been relieved in a few weeks by selenium supplementation
      as selenite. There may be a relationship between iron depletion and diffuse hair
      loss in home parenteral nutrition patients at higher risk of anaemia. A serum
      ferritin level of 70 MUg/l should be targeted when hair loss is unexplained.
      However, there is limited data correlating cessation of hair loss with iron
      therapy and insufficient evidence to recommend iron supplementation in patients
      without anaemia. Parenteral nutrition-associated biotin deficiency has not been
      reported since the vitamin has been routinely added to parenteral nutrition.
      However, marginal biotin status, associated with diffuse hair loss, could still
      be prevalent. SUMMARY: Micronutrient status is infrequently monitored and current
      recommendations for supplementation are nonspecific for hair loss in long-term
      parenteral nutrition. Studies are required to determine the incidence of marginal
      zinc, selenium, iron or biotin deficiencies that could manifest as hair loss.

PMID- 20823775
TI  - Do all sedentary activities lead to weight gain: sleep does not.
AB  - PURPOSE OF REVIEW: To discuss the benefits of having a good night's sleep for
      body weight stability. RECENT FINDINGS: Experimental studies have shown that
      short-term partial sleep restriction decreases glucose tolerance, increases
      sympathetic tone, elevates cortisol concentrations, decreases the satiety hormone
      leptin, increases the appetite-stimulating hormone ghrelin, and increases hunger
      and appetite. Short sleep duration might increase the risk of becoming obese,
      because it does not allow the recovery of a hormonal profile facilitating
      appetite control. Lack of sleep could also lead to weight gain and obesity by
      increasing the time available for eating and by making the maintenance of a
      healthy lifestyle more difficult. Furthermore, the increased fatigue and
      tiredness associated with sleeping too little could lessen one's resolve to
      follow exercise regimens. SUMMARY: Short sleep duration appears to be a novel and
      independent risk factor for obesity. With the growing prevalence of chronic sleep
      restriction, any causal association between reduced sleep and obesity would have
      substantial importance from a public health standpoint. Future research is needed
      to determine whether sleep extension in sleep-deprived obese individuals will
      influence appetite control and/or reduce the amount of body fat.

PMID- 20823776
TI  - Role of hepatic desaturases in obesity-related metabolic disorders.
AB  - PURPOSE OF REVIEW: This review aims to address the latest research on hepatic
      desaturases and metabolic disorders, with focus on stearoyl-CoA desaturase-1 (SCD
      1) indices in observational studies. RECENT FINDINGS: In animal studies, SCD-1
      inhibition protects against features of the metabolic syndrome and is associated
      with improved hepatic insulin resistance and decreased steatosis. In human
      observational studies, higher estimated hepatic SCD-1 and Delta6-desaturase
      activities predict the metabolic syndrome, insulin resistance and mortality
      whereas Delta5-desaturase index is often inversely related. However, because the
      desaturase activities in the liver and adipose tissue may not be regulated in
      parallel, it is important to define used lipid fractions when comparing studies.
      It is also important to take the background diets of the populations into account
      when comparing studies. Moreover, there may be a divergence in desaturase
      regulation depending on glycaemic control among individuals. SUMMARY: Increased
      SCD-1 indices reflecting liver desaturase activity have been associated with
      insulin resistance, fatty liver, the metabolic syndrome and mortality. However,
      it remains to be determined if high hepatic SCD-1 activity plays a direct role in
      the development of metabolic disorders or rather is a marker for an unfavourable
      diet or hepatic insulin resistance.

PMID- 20823777
TI  - Potential interest of gut microbial changes induced by non-digestible
      carbohydrates of wheat in the management of obesity and related disorders.
AB  - PURPOSE OF REVIEW: The modulation of the gut microbiota by nutrients is of
      interest in order to reverse host metabolic alterations linked to gut microbiota
      dysbiosis. This review discusses how nondigestible carbohydrates (NDC) derived
      from wheat may constitute functional cereal food products in the management of
      obesity and diabetes, notably through modulation of gut microbiota. RECENT
      FINDINGS: Recent evidences highlighted that alterations in the composition of the
      gut microbiota participate in the development of obesity. Interesting nutrients
      that target specific gut microbes (prebiotics) are able to reverse host metabolic
      alterations linked to gut microbiota dysbiosis in obese individuals. Recent data
      suggest that NDC prepared from wheat represent a new class of nutrients
      exhibiting prebiotic properties. SUMMARY: Processing technologies of wheat grain
      lead to production of original NDC characterized by specific degree of
      polymerization and degree of substitution. Those characteristics condition the
      gut compartment where fermentation occurs, the changes of bacteria composition
      and the proportion of bacterial metabolites (i.e., short-chain fatty acids)
      released in the gut. Scientists may take into consideration a key question: could
      we help control obesity and type 2 diabetes through the modulation of gut
      bacterial metabolism and/or composition by wheat-derived NDC? This opens up an
      original area in nutrition research.

PMID- 20823779
TI  - Impact of concomitant immunosuppression on the presentation and prognosis of
      patients with melanoma.
AB  - Melanoma has been reported to be susceptible to immune control, although the
      degree of impact of immunosuppression on the course of this disease is uncertain.
      The Beth Israel Deaconess Medical Center's Cutaneous Oncology Program database
      was examined to identify patients receiving immunosuppressive therapy at the time
      of melanoma diagnosis. Demographics and the stage of these patients were compared
      with the other patients in the database, and three controls matched for age, sex,
      stage, and tumor location were identified from the database for each case and
      disease outcomes for the two groups compared. Nineteen patients were identified
      with melanoma and concomitant immunosuppression in a database of 1839 patients.
      Patients were receiving immunosuppressive therapy for a variety of conditions,
      including solid organ transplant and inflammatory or autoimmune diseases.
      Compared with the remaining database, patients on immunosuppression were more
      likely to be women (84 vs. 44%) with an amelanotic primary melanoma (21 vs.
      5.3%). Patients with immunosuppression were equally likely to relapse, but more
      likely to have died of melanoma than controls (42 vs. 23%) (P=0.01, log-rank
      test). These findings suggest that immunosuppressive therapy is associated with a
      more aggressive disease course in patients with melanoma. The additional
      observation that the stage-specific recurrence rates were similar, however,
      suggests that routine dermatologic screening of immunosuppressed patients may
      lead to earlier diagnosis and improved outcomes.

PMID- 20823778
TI  - Colorectal cancer incidence rates have decreased in central Italy.
AB  - We analyzed colorectal cancer incidence data from the Tuscany Cancer Registry,
      central Italy, for the period 1985-2005. We carried out a trend analysis through
      a Joinpoint regression analysis, and summarized trends as annual percent change
      (APC) of the standardized (European standard) rates. Colorectal incidence rates
      increased until 1996 (APC=+1.4, 95% CI: 0.8-1.9), then decreased significantly
      (APC=-1.1, 95% CI: -0.8 to -0.4). The change was detected as statistically
      significant in the age group of 54+ years. Among younger individuals, we observed
      an increasing incidence until 2003. In the same geographical area, a colorectal
      screening programme has been active from 1982; it was initially based on guaiac
      faecal occult blood testing (GFOBT) and on immunological testing (IFOBT) since
      the mid 1990s. The decline in colorectal cancer incidence since 1996, in the
      whole population and especially among individuals older than 54 years, may
      suggest the effect of FOBT screening in terms of precancerous polyps removal.

PMID- 20823780
TI  - Invasive aspergillosis in cystic fibrosis: a fatal case in an adolescent and
      review of the literature.
AB  - Invasive aspergillosis is a rare complication of cystic fibrosis. In this
      article, we describe a case of an adolescent with cystic fibrosis, which was well
      controlled previously, colonized with Aspergillus fumigatus. The patient
      developed fatal disseminated aspergillosis in the absence of any preexisting risk
      factors after a short course of intravenous corticosteroid treatment.

PMID- 20823781
TI  - Cumulative cardiac toxicity of sodium stibogluconate and amphotericin B in
      treatment of kala-azar.
AB  - Kala-azar or visceral leishmaniasis is a disseminated protozoal infection caused
      by parasites of the genus Leishmania (Leishmania donovani in India). Conventional
      therapy for visceral leishmaniasis continues to be pentavalent antimony (sodium
      antimony gluconate [SAG]). Amphotericin B is widely used for SAG-unresponsive
      cases and sometimes even as a first-line drug, especially in endemic areas. With
      the conventional regimen of SAG, cardiac toxicity has been reported in 8% to 17%
      of cases with 5% to 7% of them having fatal toxicity. Cardiac toxicity is
      uncommon with amphotericin B with only few isolated reports. We report some
      patients with kala-azar in whom coadministration of SAG and amphotericin B led to
      arrhythmia and sudden death.

PMID- 20823782
TI  - The correlation between pain, catastrophizing, and disability in subacute and
      chronic low back pain: a study in the routine clinical practice of the Spanish
      National Health Service.
AB  - STUDY DESIGN: Correlation between variables measured with previously validated
      instruments. OBJECTIVE: To explore the association between catastrophizing and
      disability in patients treated for subacute or chronic low back pain (LBP) within
      routine clinical practice in Spain. SUMMARY OF BACKGROUND DATA: The influence of
      psychological variables on LBP-related disability in Southern Europe is different
      to the one in the Anglo-Saxon and Northern European cultural environments. In
      Spanish LBP patients, the influence of fear avoidance beliefs on disability is
      negligible, and catastrophizing does not mediate the improvement of disability
      caused by active education. The association between catastrophizing and dis
      ability is unknown. METHODS: Thirty-three clinicians working for the Spanish
      National Health Service in 6 primary care and 8 specialty centers, recruited 1461
      patients seeking care for subacute and chronic LBP. Patients were assessed only
      once. A linear regression model was developed to assess the percentage of the
      variance of disability explained by gender, age, chronicity status, severity of
      LBP, severity of referred pain (referred pain down to the leg), catastrophizing,
      eligible for workers' compensation (yes/no), failed back surgery (yes/no),
      radiologic findings, and treatments. RESULTS: Correlations among LBP, referred
      pain down to the leg, disability, and catastrophizing were moderate, but
      significant. The strongest one was between disability and catastrophizing (r ?
      0.520). Catastrophizing explained 28% of disability, whereas severity of LBP only
      3%. Global adjusted R of the model was 0.387. There was an association between
      some radiologic findings and treatments, and slightly higher levels of
      disability. CONCLUSION: In Southern European subacute and chronic LBP patients,
      catastrophizing correlates with dis-ability and explains approximately one-fourth
      of its variance. Further studies should assess its value as a prognostic factor
      in subacute and chronic patients.

PMID- 20823783
TI  - Cost-effectiveness of lumbar supports for home care workers with recurrent low
      back pain: an economic evaluation alongside a randomized-controlled trial.
AB  - STUDY DESIGN: Economic evaluation from a societal perspective alongside a 12
      months randomized-controlled trial. OBJECTIVE: To determine the cost
      effectiveness of wearing a lumbar support for home care workers with recurrent
      low back pain (LBP) (secondary prevention). SUMMARY OF BACKGROUND DATA: LBP is a
      large medical and economical burden. Evidence on the secondary preventive use of
      lumbar supports is sparse. METHODS: A total of 360 home care workers with a self
      reported history of LBP were randomly assigned to usual care or usual care plus
      wearing a lumbar support on working days with LBP, during a 1-year period.
      Primary clinical outcome measures were the average number of self-reported days
      with LBP, number of calendar days sick leave in general, and quality of life.
      Direct and indirect costs were measured by means of cost diaries. Differences in
      mean costs between groups, cost-effectiveness, and cost-utility ratios were
      evaluated, and cost-effectiveness planes and acceptability curves presented by
      applying nonparametric bootstrapping techniques. RESULTS: During the intervention
      period, the home care workers using a lumbar support in addition to usual care
      reported on average 54 fewer days with LBP (95% confidence interval [CI], -85 to 
      29). The estimated mean difference in sick leave was not statistically
      significant (-5.0 days per year in favor of the lumbar support group; 95% CI, 
      21.1 to 6.8). There was no statistically significant difference in quality of
      life. Direct costs were 235 euros (US$ 266) lower in the lumbar support group
      (95% CI, -386 to -79). Indirect costs were 255 euros (US$ 288) lower, but this
      was not statistically significant (95% CI, -879 to 299). CONCLUSION: Lumbar
      support seems to be a cost-effective addition to usual care for home care workers
      with recurrent LBP. For estimating the LBP-related indirect costs, it would be
      more precise when an objective measure for LBP-related sick leave would have been
      available. There is a need for more evidence to confirm these findings, also in
      other working populations.

PMID- 20823784
TI  - Total en bloc spondylectomy of the lower lumbar spine: a surgical techniques of
      combined posterior-anterior approach.
AB  - STUDY DESIGN: Ten patients with a spinal tumor of the lower lumbar spine
      underwent total en bloc spondylectomy (TES) by combined posterior-anterior
      approach. The oncological and neurologic results are analyzed. OBJECTIVE: To
      describe the surgical technique and evaluate the clinical outcome of this
      surgery. SUMMARY OF THE BACKGROUND DATA: TES at lower lumbar spine is technically
      challenging because of its anatomy such as the presence of major vessels and
      lumbosacral plexus nerves. METHODS: Six aggressive benign tumors and 4 solitary
      spinal metastases involving L4 or L5 were treated. The approache of operative
      procedure are discussed as follows: Posterior approach: Dissection of the lumbar
      nerve roots to the conjunction of the adjacent nerves were performed after en
      bloc laminectomy by T-saw pediculotomy. The psoas muscle was dissected away, from
      the vertebral body. The posterior halves of the anterior column at the
      craniocaudal adjacent levels of the lumbar tumor were cut. Anterior approach:
      Major vessels were dissected from the vertebral body. Anterior halves of the
      anterior column were cut at the corresponding levels. The tumor vertebral body
      was removed en bloc, followed by anterior spinal reconstruction. RESULTS: Seven
      of 10 cases had no evidence of disease at 57 months on average, 1 case was alive
      with disease at 66 months, 1 case had death of disease at 42 months, and 1 case
      had death of another disease at 14 months after surgery. All patients improved or
      preserved neurologic in the last follow up. The resected specimen of vertebral
      bodies and laminae showed marginal or wide margin in all cases, although pedicles
      showed intralesional margin in 8 cases. No local recurrence was observed during
      lifetime with mean 52 months. CONCLUSION: TES for spinal tumor of L4 or L5
      preserving lumbar nerves was achieved by combined posterior- anterior approach.

PMID- 20823785
TI  - Reliability and validity study of the Finnish version 2.0 of the oswestry
      disability index.
AB  - STUDY DESIGN: Prospective clinical validation study. OBJECTIVE: The aims of this
      study were to translate into Finnish and culturally adapt and study the psycho
      metric properties of the Oswestry Disability Index (ODI) version 2.0. SUMMARY OF
      BACKGROUND DATA: The ODI is one of the most commonly reported back-specific
      disability questionnaires. It is widely used both in clinical work and in medical
      studies. To date, no validated Finnish version of the ODI version 2.0 has been
      reported. METHODS: The ODI version 2.0 was translated into the Finnish language.
      A total of 115 patients with back pain, referred by the primary care physician to
      the outpatient clinic of the department of physical medicine and rehabilitation,
      were recruited for this study. The patients answered a questionnaire package that
      included the Finnish ODI 2.0, Back Pain Questionnaire for Visual Analogue
      Assessment (Million-VAS), Visual Analogue Scales of back and leg pain (VASback,
      VASleg), the Depressions Scale, and a question on their subjectively perceived
      health. The package was administered twice; 2 weeks before and at the arrival to
      the clinic. RESULTS: Reproducibility of the ODI was 0.90 (95% confidence interval
      [CI] = 0.85-0.94) and the internal consistency was 0.86 (95% CI = 0.81-0.90).
      Factor analysis showed that the ODI was loaded on 2 factors, which explained 51%
      of the total variance. In testing convergent validity ODI correlated with Million
      VAS, r = 0.75 (95% CI = 0.64-0.84); VASback, r = 0.48 (95% CI = 0.32-0.62); and
      VAS leg, r = 0.41 (95% CI = 0.23-0.57). CONCLUSION: The Finnish ODI version 2.0
      proved to be a valid and reliable instrument that showed psychometric properties
      comparable with the original English version. Therefore, it can be used in
      assessing the disability among Finnish-speaking patients with back pain for both
      clinical and scientific purposes.

PMID- 20823787
TI  - Evidence based and personalized review of perioral dermatitis therapy.

PMID- 20823788
TI  - Evidence based review of perioral dermatitis therapy.
AB  - Perioral dermatitis presents as an eruption of erythematous papules, pustules and
      papulovesicles, most frequently seen in young women. Oral tetracyclines have been
      considered the first line treatment for years. However, recent publications have
      found newer agents to be efficacious. The authors performed a review of the
      available data in order to determine the strength of evidence supporting
      published therapies. A Pubmed and Cochrane Library database search for all cases,
      case series, and clinical trials dealing with the treatment of perioral
      dermatitis in English. Most cases of perioral dermatitis are self-limited, if the
      possible exacerbants of cosmetics and topical corticosteroids are discontinued
      ("zero therapy"). Many trials support the use of oral tetracyclines as a first
      line medication, as it significantly shortens the time to papule resolution.
      Topical erythromycin also reduces the time to resolution, but not as quickly.
      Topical pimecrolimus does not appear to decrease the time to complete resolution,
      but it does rapidly reduce the severity of the disease, particularly if prior
      corticosteroid use has occurred. The evidence supporting topical metronidazole,
      which is frequently used to treat perioral dermatitis in children, is relatively
      weak and supported only by case series and a trial showing it to be inferior to
      tetracycline. The evidence most strongly supports the efficacy of zero therapy,
      topical pimecrolimus, oral tetracycline, and topical erythromycin.

PMID- 20823789
TI  - Photoaging: the role of oxidative stress.
AB  - Our skin suffers from daily exposure to oxidative stress, primarily from exposure
      to the sun's damaging ultraviolet (UV) rays. This results in the appearance of
      premature aging. The mechanisms of this photodamage to all layers of the skin by
      the various wavelengths (UVB and UVA) will be clarified. Recent research further
      demonstrates a synergistic enhancement of oxidative damage when the skin is
      exposed to UVA in combination with environmental urban pollutants (including
      cigarette smoke). The fact that photoaging is largely caused by oxidative damage
      is confirmed by the demonstration that treatment with topical antioxidants can
      prevent and even partially reverse UV-induced photodamage. Research
      substantiating the efficacy of vitamins C and E and of selenium will be reviewed.

PMID- 20823790
TI  - Advances in photodynamic therapy. A review.
AB  - Photodynamic therapy (PDT) has been pioneered in dermatology at the beginning of
      the 20th century. Today, cutaneous treatments are the most common applications of
      PDT. Originating from cancer therapy, recent developments have widened the
      therapeutic spectrum, and now PDT indications range from inflammatory disorders
      to cosmetic applications. With several photosensitizers approved by regulatory
      agencies around the world, PDT continues demonstrating its inherent versatility.
      This review concentrates on aminolevulinic acid-based PDT regimens in
      dermatology. Recent research has helped to enhance the treatment efficacy of PDT
      and to further exploit its potential. Evolving strategies are being tested at
      present experimentally that will increase the power and diversity of cutaneous
      PDT. Ultimately these regimens will affect future development in clinical
      applications.

PMID- 20823791
TI  - Photodynamic inactivation of microorganisms as an innovative approach to kill
      mucocutaneous and skin microorganisms.
AB  - In 2002, the first documented case of a vancomycin-resistant S. aureus strain
      (MIC>or=32 microg/mL) was reported. Nowadays approximately 20% of S. aureus
      isolates in Europe are reported as methicillin-resistant. Besides bacteria
      infections, the emergence of fungal infections has increased considerably due
      factors such as immunosuppressive medications, broad-spectrum antibiotics,
      neutropenia and HIV infections. These tremendous effects underline the importance
      and the urgency to develop new alternative treatment approaches that are
      effective against infections caused by multi-resistant pathogens. Photodynamic
      inactivation of microorganisms (PDIM) is considered as a new approach, which
      utilizes a photoactive dye, oxygen and visible light to generate reactive oxygen
      species, which damage irreversible the pathogens during illumination. Cutaneous
      diseases caused by methicillin-resistant S. aureus or by fungal species are
      ideally suited to the treatment by PDIM for eradicating localized infections and
      for modulating wound healing due to the ability to deliver photosensitizer and
      light with topical application. The challenge of PDIM is to find a therapeutic
      window in vivo where multi-resistant microorganisms can be killed efficiently,
      thereby not harming the surrounding tissue or disturbing the residual bacteria
      flora of the tissue. Different chemical classes of photosensitizers have
      demonstrate their potential to photoinactive Gram(+), Gram(-) and fungal cells.
      This review will focus on general photobiological and photochemical aspects of
      microbial inactivation by the photodynamic effect as well as to summarize the
      current knowledge about the possible application modalities of PDIM on localized
      infectious diseases in dermatology.

PMID- 20823792
TI  - Photodynamic therapy: mechanism of action and role in the treatment of skin
      disease.
AB  - The combination of lesion ablation with excellence in cosmetic outcome has
      allowed photodynamic therapy (PDT) an ever increasing role in the treatment of
      diseases of the skin. As currently practiced, PDT employs a photosensitizing
      agent that when activated by light energy creates a photodynamic reaction that is
      cytotoxic and vasculotoxic. The relative simplicity of therapy with its ability
      to achieve high response rates has brought PDT to a worldwide audience not only
      for oncologic indications but far more commonly to non oncologic indications.
      This paper will review the mechanism of action for PDT and highlight the
      versatile clinical outcomes reported from the peer reviewed literature.

PMID- 20823793
TI  - Photoprotection with clothing and sunscreens.
AB  - Skin cancer is an ever-expanding global health issue. UV radiation is the main
      etiological agent of most types of skin cancer. Photoprotection is critical to in
      skin cancer prevention. Sunscreens and physical barriers are the two primary
      photoprotective measures. This review summarizes current options in
      photoprotection, including physical barrier such as shade and clothing as well as
      sunscreens. In addition we look at how these photoprotective measures have
      influenced skin cancer rates and what can be done to improve the efficacy of
      existing photoprotective agents and devices.

PMID- 20823794
TI  - Photoprotection: update in UV-filter molecules, the "new wave" of sunscreens.
AB  - In this review, we provide a wide, non-comprehensive overview of the latest
      trends in protection against the deleterious effects of the sun. The review is
      divided into physical blockade of UV photons, UV photon absorption and/or
      reflection provided by topical sunscreens and topical antioxidant compounds. The
      last section is devoted to the newest generation of dietary photoprotective
      compounds. Possible mechanisms, particularly antioxidant, are discussed.

PMID- 20823795
TI  - Photodynamic therapy for cosmetic uses on the skin: an update 2010.
AB  - The utilization of photodynamic therapy (PDT) in the United States has reached an
      all-time high with many clinicians utilizing this form of therapy for a myriad of
      dermatologic disorders. World-wide, PDT is now being introduced to a wider
      audience. The purpose of this manuscript is to review PDT, from its history to it
      current uses and indications, and to expand upon its proper use and after care,
      to minimize any potential adverse events, and to make PDT treatments useful and
      effective for all of our patients. Two photosensitizers are now routinely
      available in the US and we will review both of these sensitizers, their FDA and
      off-label uses, and their affects on the skin and how they have made a positive
      effect in dermatology.

PMID- 20823796
TI  - Exacerbation of allergic contact dermatitis during immunosuppression with
      cyclosporine A.
AB  - Allergic contact dermatitis (ACD) is one of the commonest occupational diseases
      in industrialized countries, where it comprises 20-70% of all occupational
      diseases. Recent studies found out the top ten allergens, but there are some
      differences in their frequency in relation to gender and age of patients:
      Myroxylon pereirae and Carba mix resulted the most prevalent allergens in men,
      while in women the most common sensitizers were nickel sulfate, PPD, fragrance
      mix and cobalt chloride. ACD is an inflammatory skin disease caused by repeated
      skin exposure to contact allergens, in which the lesions are due to T CD8+ cells
      in a type IV, delayed or cell-mediated, immune reaction. The typical skin lesions
      of ACD in general outburst in contact areas with the specific allergens and they
      are erythematosus-squamous lesions with other little differences in relation to
      localization, for example edema, vesicular-exuding lesions or onychodystrophy.
      Different treatment options exist and are applied according to the severity of
      the lesions. Topical treatments consist of bland emollients, corticosteroids
      ointments, topical immunomodulators such as tacrolimus and pimecrolimus
      ointments, coal tar and derivatives and irradiation with ultraviolet lights or X
      rays; while azathioprine, methotrexate, cyclosporine A, oral retinoids or oral
      corticosteroids represent systemic options of therapy. Nevertheless, the control
      of chronic ACD is often difficult, overall in patients with chronic ACD.

PMID- 20823797
TI  - Clinical aspects of advanced stage lipo-lymphedema: case report.
AB  - The aim of the current study was to alert about dermatological alterations in the
      clinical evolution of lipo-lymphedema. The case of a 48-year-old patient is
      reported with clinical diagnosis of stage II lipo-lymphedema treated in the
      Angiology and Vascular Surgery Service of FAMERP. On physical examination the
      edema was hard, not reversible during rest, with nodules in the lower one-third
      of the limbs and a positive Stemmer's sign. The sizes of the nodules were
      different between legs. This report stresses the clinical findings and the
      differences in each disease. Additionally a review of publications is presented.
      The dermatological changes occurring in the evolution of lipedema may be
      associated with the evolution of lipo-lymphedema.

PMID- 20823798
TI  - An intriguing case of Prurigo pigmentosa in a Sicilian young patient.
AB  - Prurito pigmentosa is an inflammatory disease mainly reported by Japanese
      dermatologists. We report a case of Prurigo pigmentosa observed in a Sicilian
      young patient affected by intellectual disability. In the past, we had already
      observed and reported some cases of Prurigo pigmentosa in patients living in
      Sicily. The differential diagnosis, the treatment of the disease, the role of
      chronic intake of psychodrugs and the possible relation to G6PD deficiency of
      this patient are pointed out.

PMID- 20823799
TI  - Umbilical warts.

PMID- 20823800
TI  - A case of midline destructive lesions in a cocaine snorter mimicking Wegener's
      granulomatosis and nasal-type natural killer/T-cell lymphoma.

PMID- 20823801
TI  - Potential utility of daphnetin as a novel treatment for pemphigus vulgaris.

PMID- 20823803
TI  - Performing renography in children with antenatally detected pelvi-ureteric
      junction stenosis: errors, pitfalls, controversies.
AB  - The aim of this work is to present to the reader the practical experience of
      three clinicians having actively participated to the publication of the
      guidelines on renography in children. The present publication should be
      considered as a practical guide. We have underlined good practice, obvious errors
      to avoid, common pitfalls which might be overlooked, some items for which more
      than one reasonable solution exists and finally a few controversial points, for
      which there is still no agreement and no solid evidence to resolve these issues.
      This paper is only focused on the aspects of acquisition and processing and will
      not cover the clinical aspects, namely the interpretation of the renogram in
      terms of renal obstruction or, more precisely, in terms of risk of renal
      deterioration.

PMID- 20823804
TI  - Molecular biology and nuclear medicine in pediatric hydronephrosis.
AB  - Pediatric hydronephrosis may correspond to very different clinical situations,
      ranging from fully benign reversible dilatation to severe obstructive
      nephropathy. The genetic research is difficult, mainly because the condition is
      probably polygenic and the embryology of the urinary system is very complex and
      depends on a multifaceted interaction of genetic and environmental factors.
      Molecular biology has gained new insights in the complicated urinary system and
      in the mechanisms of obstructive nephropathy. Some mediators (tumor growth
      factor, tumor necrosis factor, renin angiotensin system, etc.) could be
      considered molecular markers of obstruction and it has been proposed to introduce
      them in clinical decision making, in order to make an accurate selection of
      patients needing surgical correction. Scintigraphy has been a standard procedure
      in the management of pediatric hydronephrosis for decades and has been used in
      many clinical studies designed to evaluate the role of selected molecular markers
      in clinical settings. The relationships between scintigraphic parameters and
      molecular mediators seems promising, in particular for the evaluation of the
      Reanin Angiotensin System, which plays many roles in the natural history of
      pediatric hydronephrosis. Angiotensin up-regulation is a turning point in many
      pediatric hydronephrosis and can be unveiled by captopril scintigraphy, which
      allows a timely diagnosis of obstruction, before irreversible parenchymal injury
      and loss of renal function.

PMID- 20823805
TI  - Gastro-esophageal studies in relationship to respiratory problems.
AB  - Gastroesophageal reflux represents a physiological phenomenon in the first year
      of life. The reflux associated with clinical complications is defined as
      "gastroesophageal reflux disease" (GERD), that may be esophageal or extra
      esophageal, as is for respiratory problems. Nuclear medicine investigations have
      given an important contribution to the diagnostic assessment and therapeutical
      management of GERD in children, by means of the following procedures:
      scintigraphy of the gastroduodenal transit and reflux detection, scintigraphic
      quantification of gastric emptying, scintigraphy of the esophageal transit,
      radioisotopic salivagram, scintigraphy of lung perfusion, ventilation and of
      mucociliary clearance. All of these investigations are among the less irradiating
      nuclear medicine procedures, therefore particularly adapted to paediatrics. The
      main clinical advantages of this body of information include: improvements in the
      management of many asthmatic children, surgical anti-reflux intervention success
      rate increase, prompt regional lung alterations detection for preventing stable
      tissue damage, and many others.

PMID- 20823806
TI  - Dose reduction in pediatric hybrid and planar imaging.
AB  - Dose reduction in pediatric nuclear medicine involves many aspects of nuclear
      imaging. The computed tomography (CT) parameters used during the new hybrid
      imaging procedures, positron emission tomography (PET)/CT and single photon
      emission computed tomography (SPECT)/CT, involve trade-offs between image quality
      and effective dose. In this setting, CT may be used for diagnostic quality
      imaging, localization of scintigraphic abnormalities or attenuation correction
      only, with markedly different radiation exposures for each technique. The nuclear
      physician must select administered activities for PET and single photon imaging
      that provide quality imaging results at the lowest possible radiopharmceutical
      dosage. These administered activities must be adjusted appropriately for patient
      mass or age. Physical differences between PET and single photon imaging may
      require different adjustments for patient size. Dynamic imaging protocols should
      be reviewed to assure that frame rates appropriately track physiologic events and
      facilitate low administered activities. Optimal dose reduction in pediatric
      nuclear imaging requires attention to CT exposure parameters, administered
      activity and imaging protocols.

PMID- 20823807
TI  - Modern nuclear medicine evaluation of neuroblastoma.
AB  - The neuroblastoma is an embryonic tumor of the peripheral sympathetic nervous
      system, and is metastatic or otherwise high risk for relapse in nearly 50% of
      cases, with a long-term survival of <40%. Therefore, exact staging with
      radiological and nuclear medicine imaging methods is crucial for finding the
      adequate therapeutic choice. The tumor cells express the norepinephrine
      transporter, which makes metaiodobenzylguanidine (MIBG), an analogue of
      norepinephrine, an ideal tumor specific agent for imaging. On the other hand,
      MIBG imaging has several disadvantages as limited spatial resolution, limited
      sensitivity in small lesions, need for two or even more acquisition sessions, and
      a delay between the start of the examination and result. Most of these
      limitations can be overcome with positron emission tomography (PET) using
      different radiotracers. Furthermore, MIBG imaging is not sufficient for operative
      or biopsy planning. With this regard, a combination with morphological imaging
      methods is indispensable. This article will discuss the therapeutic strategy for
      primary and follow-up diagnosis in neuroblastoma using different nuclear medicine
      and radiological imaging methods as well as multimodality imaging.

PMID- 20823808
TI  - FDG-PET/CT in pediatric solid tumors.
AB  - Positron emission tomography/computed tomography (PET/CT) has become an important
      imaging modality in the non-invasive evaluation and monitoring of children with
      known or suspected malignant diseases. In sarcoma patients, [18F]FDG (FDG) PET
      and FDG PET/CT is useful in staging, therapy monitoring, and detection of
      relapse. However, FDG PET has been proven to be less sensitive than chest CT in
      the detection of pulmonary metastases derived from sarcoma. This disadvantage has
      been overcome using a PET/CT scanner. In neuroblastoma patients, PET using FDG is
      indicated in MIBG-negative cases. Furthermore, there are specific PET tracers for
      tumors of the sympathetic nervous system, such as [11C]Hydroxyephedrine (HED) and
      [18F]-labeled dihydrophenylalanine (F-DOPA), which can be used for PET/CT imaging
      for detection of disease, staging and monitoring therapy. However, there are only
      few studies using specific PET tracers in neuroblastoma patients. In other
      pediatric malignancies including germ cell tumors and hepatoblastoma PET and
      PET/CT may be helpful in individual cases, but the literature in these entities
      is limited so far. Although publications on the additional value of the combined
      PET/CT compared to both stand-alone modalities are still limited in pediatrics,
      it can already be anticipated that the combination of morphological and
      functional information obtained by integrated PET/CT will improve the accuracy of
      staging and will change patient management in a significant number of pediatric
      patients.

PMID- 20823809
TI  - Therapeutic nuclear medicine in pediatric malignancy.
AB  - The following review aims to provide contemporary information on therapeutic
      nuclear medicine procedures in paediatric malignancies. Neuroblastoma is the most
      common paediatric extra cranial solid cancer characterized by meta
      iodobenzylguanidine (mIBG) avidity in >/=90% of patients. There exists
      approximately a 30-year experience with I-131-mIBG treatment. Ongoing efforts
      include a more standardized approach including dosimetric data for patient
      selection and treatment guidance of I-131-mIBG therapy. Neuroendocrine tumours
      (NETs) are very rare neoplasms in the paediatric population accounting for <1% of
      all paediatric malignancies. These neoplasms are characterized by the presence of
      neuroamine uptake mechanisms and/or peptide receptors at the cell membrane. These
      features constitute the basis of the clinical use of peptide receptor
      radionuclide therapy (PRRNT) using radiolabeled somatostatin analogues.
      Osteosarcoma is the most common primary bone tumour in children usually treated
      with chemotherapy and surgery. In palliative situations bone seeking radionuclide
      therapies (strontium-89 [Sr-89], rhenium-186 hydroxyethylene diphosphonate [Rh
      186 HEDP] and Samarium-153-ethylene diamine tetramethylene phosphonic acid [Sm
      153-EDTMP]) may be offered to patients with painful metastatic osteosarcoma or in
      case of recurrent bone sites inaccessible to local therapies (surgery, external
      irradiation). Thyroid cancer is a rare childhood malignancy with an approximate
      incidence of 0.54 per 100000 per year but is the most frequent tumour of
      endocrine glands in children and adolescents. Management includes radioiodine
      therapy but there are some distinct differences in comparison to adult thyroid
      cancer management.

PMID- 20823810
TI  - Potential clinical role of 18F FDG-PET/CT in detecting hip prosthesis infection:
      a study in patients undergoing two-stage revision arthroplasty with an interim
      spacer.
AB  - AIM: We evaluated the potential role of [18F]fluorodeoxyglucose-positron emission
      tomography/computed tomography ([18F]FDG-PET/CT) to identify latent infections at
      the site of an interim hip spacer after resection arthroplasty for hip prosthesis
      infection. METHODS: Twelve patients with an interim hip spacer following
      resection arthroplasty (Group A) were investigated. Twelve patients with painful
      primary hip prostheses served as controls (Group B). All underwent PET/CT before
      surgery. Both non-attenuation-corrected (NAC) and attenuation-corrected (AC)
      images were analyzed. Serum C-reactive protein (CRP) levels were measured in 22
      patients. Elevated CRP level was defined as >/=10 mg/L. The diagnosis of
      infection was based on the results of intraoperative tissue cultures,
      intraoperative pathology, and clinical follow-up. RESULTS: FDG-PET/CT had 100%
      sensitivity and 100% negative predictive value for detection of latent infection
      in both groups. However, there were 4 and 3 false positive cases in Group A and
      Group B, respectively. Specificity improved from 50% to 62.5% in Group A, and
      from 62.5% to 87.5% in Group B when using NAC instead of AC. Seventeen patients
      had CRP values >/=10 mg/L, but only 8 were true positive for infection. FDG
      PET/CT ruled out infection in 77.8% (7/9) of false-positive cases identified by
      CRP levels. CONCLUSION: FDG-PET/CT is highly sensitive to detect latent
      infections in prosthetic hips and in interim hip spacers. The high negative
      predictive value of PET/CT scans is useful to rule out infections in patients
      with persistently elevated CRP levels. PET/CT might serve as an auxiliary tool to
      exclude latent infections in patients posing a clinical diagnostic dilemma.

PMID- 20823811
TI  - Evaluation of 99mTc-UBI 29-41 scintigraphy for specific detection of experimental
      multidrug-resistant Staphylococcus aureus bacterial endocarditis.
AB  - AIM: The aim of this paper was to test the ability of technetium-99m labelled
      synthetic peptide UBI 29-41 scintigraphy (99mTc-UBI 29-41), composed of the
      antimicrobial peptide ubiquicidin, specifically targets microorganisms in to
      discriminate between infected and uninfected endocarditis using a rat model
      previously validated. METHODS: 99mTc-UBI 29-41 scintigraphy was evaluated for its
      accumulation in infective endocarditis (IE) with multidrug resistant
      Staphylococcus aureus (MRSA) performed in an experimental rat model, resembling
      early endocarditis in humans. Serial planar scintigraphic and biodistribution
      analysis of infected vegetations are compared to rats with sterile vegetations.
      Heart-to-lung uptake ratios (T/NT ratios) were calculated in both with in-vivo
      scintigraphy and in ex vivo tissue samples. RESULTS: Bacterially infected
      vegetations were already observed at 15 min after injection of 99mTc-UBI 29-41
      while no significant uptake was observed in sterile vegetations. Moreover, a good
      correlation (R2=0.819) was calculated between T/NT ratios of 99mTc-UBI 29-41 and
      the number of viable MRSA present in the infected vegetation. There was no
      correlation between the 99mTc-UBI 29-41 uptake and the weight of the vegetations
      in either case. CONCLUSION: In this experimental study in rats, planar 99mTc-UBI
      29-41 scintigraphy permitted early and specific detection of MRSA induced
      endocarditis. Furthermore, accumulation of the tracer depends on the number of
      viable MRSA and not on the weight of the vegetation. This proof of principle
      offers much promise that 99mTc-UBI 29-41 scintigraphy can be a dedicated non
      invasive imaging tool for the early detection of infective endocarditis. Finally,
      this model has to be further evaluated with state-of-the art small imaging
      modalities.

PMID- 20823812
TI  - FDG PET and 90Y ibritumomab tiuxetan in patients with follicular lymphoma.
AB  - AIM: Despite its established utility in non-Hodgkin's lymphoma, not much is
      reported on FDG positron emission tomography (PET) with respect to
      radioimmunotherapy (RIT). In this paper we investigate its value in patients
      affected by follicular lymphoma (FL) before and after treatment with
      [90Y]Ibritumomab Tiuxetan (Zevalin(R)). METHODS: We evaluated 38 relapsed or
      refractory FL patients. All had a PET scan performed before and 3 months after
      radioimmunotherapy. Final assessment was done 9 months post-RIT, including
      clinical evaluation, other imaging techniques and/or biopsy, when necessary.
      RESULTS: At the first PET scan 20 patients out of 38 had a limited disease (nodal
      involvement on one side of the diaphragm: 7 above and 13 below), 11 patients had
      nodal findings on both sides of the diaphragm and the remaining 7 patients had
      both nodal and extra-nodal findings. At three months post-RIT, 21 patients (55%)
      were in complete remission, 13 patients (34%) had a partial response (PR) and
      four patients (11%) had a progression disease (PD). The corresponding rates at
      final assessment were all consistent with the 3-month evaluation: 55% CR, 13% PR
      and 32% PD. FDG PET scan revealed maximal predictive values. When comparing the
      disease extent at relapse and the response to treatment, we could testify a
      higher rate of CR (75%) in patients with limited disease, while in patients with
      diffused nodal and/or extra-nodal findings, it was more frequent a PR or PD
      (66%). CONCLUSION: Our data are concordant with the expected results on RIT, and
      FDG PET is confirmed to be useful in assessing treatment response. Potential
      correlation can also be picked out between the disease extent at relapse and the
      CR rate, with reasonable PET predictivity for the final outcome.

PMID- 20823813
TI  - [Simultaneous surgery of competing cardio-vascular and malignant diseases of
      lungs and mediastinum].
AB  - 36 patients were operated on lung cancer (30), trachea (1), lung colon cancer
      metastases (1), left atrium paraganglioma, bronchogenic thymic cyst (1) and lung
      tuberculoma (2). Competing cardio-vascular diseases were as follows: coronary
      heart disease (30), valve failure (3) and critical stenosis of internal carotid
      artery (3). Simultaneous operations were performed in 13 (36.1%), consecutive -
      in 23 patients. Non-complicated postoperative period was registered in 19
      patients. 6 of them had simultaneous surgery and 13 were operated on
      consecutively. Overall mortality rate was 8.3%; among patients operated on
      simultaneously it was 15.4%, among patients of the second group - 4.3%. There
      were no postoperative deaths among patients, operated first on cardio-vascular
      system.

PMID- 20823814
TI  - [Sclerotherapy for the treatment of thyroid functional anatomy].
AB  - Comparative efficacy of ethanol and ethoxysclerol in sclerotherapy was studied
      among 37 patients with thyroid functional autonomy. It is shown that
      ethoxysclerol exceeds ethanol in efficiency of treatment, doesn't lead to
      depressed function of treated thyroid lobe and is better tolerated. Thereby
      ethoxysclerol should be always used as a sclerosant in patients with hormonal
      disturbances and multiple "hot" nodules.

PMID- 20823815
TI  - [Duodenal pancreatic-preserving resections with common bile and pancreatic ducts
      replantation by cystic form of duodenal dystrophy].
AB  - Two patients with cystic dystrophy of duodenum and chronic inflammation of
      duodenally ectopic pancreatic tissue were successfully operated on. Both cases
      clinically demonstrated abdominal pain and duodenal obstruction. Absence of
      substantial tissue changes in "main" pancreas allowed execution of pancreas
      preserving operation. Thus, subtotal duodenectomy was performed in the first
      patient. The second patient had resection of vertical branch of the duodenum with
      intestinal fragment replacement. Extensive periorganic fibrosis in both cases
      substantially complicated verification of anatomic structures and dissection.

PMID- 20823816
TI  - [The use of modified diagnostic scale in patients with acute appendicitis].
AB  - The diagnostic scale of acute appendicitis was combined using literature review
      and retrospective analysis of patients' data. Clinical symptoms, laboratory tests
      and ultrasound investigation were comprehensively analyzed. Thus, all patients
      could be divided in three groups: 1st group (1-3 points according to the used
      scale) had low possibility of the acute appendicitis; 2nd group (4-7 points)
      united patients, requiring further diagnostic challenges and dynamic follow-up;
      3rd group (8 points and more) had patients, who should have been operated on.
      Intraoperative view and histological investigation of the appendix were
      considered as reference diagnostic methods. Thereby, sensitivity, specificity,
      accuracy and prognostic value of positive and negative results the suggested
      diagnostic scale were 87,0, 96,7%, 91,3, 94,0 and 89,2%, respectively. Number of
      vain appendectomy was 12,3%.The scale allows to perform the right surgical
      treatment tactics with no regard of personal doctor's experience.

PMID- 20823817
TI  - [Effects of inguinal hernioplasty mesh implant on reproductive function].
AB  - In vivo experiment involved 95 white breedless male rats of pubertal age. The
      animals were divided in three groups: 1st group had unilateral hernioplasty with
      mesh implant; 2nd group had bilateral mesh implantation and 3rd group had animals
      with hernioplasty with lavsan thread. The results were assessed with the use of
      morphological method, the state of reproductive organs - with the use of
      biological method and compared with the control (intact) group. Stable
      progressive increase of thickness of epithelium and spermatic duct wall during
      the whole observation time was registered after hernioplasty with mesh
      implantation. In the group after hernioplasty with lavsan thread the above
      mentioned changes returned to normal values by the end of the first month after
      the operation. Disorders of the reproductive system in animals after bilateral
      mesh implantation turned out to be essential and resulted in sterility within the
      whole time of the observation. Mildly decreased or average fertility was observed
      among animals after unilateral mesh implantation and hernioplasty. Notably, that
      after hernioplasty with lavsan thread, fertility was sufficient. The study
      demonstrated the negative influence of mesh implant on spermatic duct structure,
      which may cause infertility.

PMID- 20823818
TI  - [Prevention and treatment of hepatorenal syndrome by acute intestinal
      obstruction].
AB  - Results of treatment were analyzed in 358 patients with acute bowel obstruction
      resulted from a variety of causes. Algorithm for control of liver and renal
      function disturbances in dynamics was estimated basing on the markers for
      hepatorenal failure. It is shown that differentiated approach to extracorporal
      detoxification combined with enterosorbtion and complex therapy allows preventing
      hepatorenal failure and decreasing lethality and terms of hospitalization.

PMID- 20823819
TI  - [Classification of tangential (thoracoabdominal) gunshot wounds].
AB  - 79 patients with gunshot bullet wounds of thorax and abdomen were observed.
      Thoracoabdominal wounds were observed in 37 cases, abdominothoracic wounds - in
      35 cases. 7 cases of longitudinal non-penetrating thoracic and abdominal wounds
      were particularly investigated. The wound canal started in soft tissues of
      anterior thoracic wall and passed through the thick layers of anterior abdominal
      wall to the perineum. Lateral blow due to high kinetic energy of bullets caused
      severe damage of the ribs, lungs and abdominal organs without diaphragm lesions.

PMID- 20823820
TI  - [Treatment of abdominal sepsis].
AB  - 129 patients with abdominal sepsis were divided in two groups. Patients of the
      1st group (n=68) were treated according to the accepted standard. Patients of the
      2nd group received the same treatment, but after germ translocation to the
      abdominal cavity and blood, immunoglobulin blood titer detection, drugs were
      administered through the cannulated umbilical vein straight to the portal system.
      Blood samples from ulnar and portal veins and microbiological samples from gut
      lumen showed similar results in patients with sepsis, proving the phenomenon of
      bacterial translocation. Histological analysis of liver biopsy demonstrated
      affection of both hepatocites and reticuloendothelial system of the liver by
      sepsis. The use of intraportal drug administration decreased mortality from 27.9%
      (1st group) to 16.3% (2nd group).

PMID- 20823821
TI  - [Current approaches to treating acute gastroduodenal ulcer bleedings].
AB  - The aim of the work was analysis of treatment of 560 patients with a
      gastrointestinal bleeding from acute ulcers. For estimation of patients was used
      universal integrated scale APACHE III. Tactics of treatment depend on secretory
      functions of a stomach and group of polyorganical difunction. At 428 (76,5%)
      patients with acute ulcers on the background increase secretion of stomach was
      treatment antysecretion therapy. At 132 (23,5%) patients with acute ulcers on the
      background of normal ore decrease secretion of stomach was treatment Cytoflavin -
      the metabolic preparation possessing antyoxidation, cytoprotection and
      immunomodulaytion activity. For studying antyoxidation and antihypoxation actions
      of Cytoflavin estimated of microcirculation mucous of a stomach with the laser
      Doppler floymetrya before course of treatment, observed increase of index
      efficiency of microcirculation and increase a blood-groove in a stomach at
      patients with acute peptic ulcers on a background of treatment of Cytoflavin.
      After course of treatment of Cytoflavin decrease in points on system APACHE III
      on 5,5-25% at all patients that has led to decrease mortality on 20% in this
      group of patients.

PMID- 20823822
TI  - [Axonopathy in the pathogenesis of multiple sclerosis, peripheral diffuse and
      local motor neuropathies and motor neuron disease].
AB  - Two hundreds and seventy-six patients including 43 patients with multiple
      sclerosis, 24 - with acute inflammatory demyelinating polyneuropathy (AIDP), 144 
      with chronic inflammatory demyelinating polyneuropathy (CIDP), 27 - with motor
      multifocal neuropathy (MMN), 38 - with lateral amyotrophic sclerosis (LAS) have
      been examined. Symptoms of axonal degeneration, manifested in denervation
      phenomena in both clinical and instrumental studies (electromyography,
      transcranial magnetic stimulation, MRT), were revealed in all groups of patients.
      The formation of excitation conduction blocks is an universal pathophysiological
      mechanism of the axonopathy development in AIDP, CIDP, MMN and LAS. Symptoms of
      axonopathy and peripheral demyelinization in patients with multiple sclerosis and
      LAS suggest the possibility of transformation of immunopathological process from
      the central nervous system to the peripheral one.

PMID- 20823823
TI  - [Hyperkinetic symptoms in children and adolescents with psychosomatic disorders].
AB  - Authors studied 151 patients with psychosomatic diseases with attention deficit
      of different severity and hyperkinetic disorders. Based on the results obtained
      in the study, it was suggested an affective- disontogenetic conception of
      hyperkinetic disorders in children and adolescents. A significant role of both
      biological and psychosocial factors as well as gender and age differences in the
      development and formation of activity and attention disorders is emphasized. The
      frequency of these factors was correlated with clinical specifics of hyperkinetic
      disorders. The correlation between specifics of hyperkinetic disorders and
      affective disorders (subdepression) was confirmed by the high effectiveness of
      differential psychopharmacotherapy with antidepressants.

PMID- 20823824
TI  - [Effect of early correction of energy and free-radical homeostasis on the
      clinical-morphological presentation of cerebral infarction].
AB  - A randomized comparative prospective 35-day clinical-instrumental trial of 30
      patients with an ischemic hemispheric stroke hospitalized on the first day of
      disease was carried out. In addition to basic therapy, 16 patients of the main
      group were treated with the antioxidant power-normalizing drug cytoflavin used in
      dosage 20 ml/day intravenous in drops from the 1st to 10th day and 2 tablets
      twice a day from the 11th to 35th day. Fourteen patients of the comparison group
      received basic therapy only. Patient's state was assessed at 0-24 h and 5, 11,
      21, 35 days of stroke. Assessment of neurological status (the Glasgow Coma Scale,
      the NIH stroke scale, a short version of MMSE), brain MRI (brain lesion volume),
      a study of antioxidant stress markers, assessment of functional outcome (the
      Barthel index and the modified Rankin scale) were conducted. The early active
      correction of power and free radical homeostasis by cytoflavin improved the
      dynamics of brain morphological changes and free-radical changes that was
      correlated with the activation of consciousness and reduction of neurologic
      deficit that resulted in the decrease of disability.

PMID- 20823825
TI  - [Torin (sertraline) in the treatment of depressive and obsessive-compulsive
      disorders in children].
AB  - Thirty-seven patients, aged from 7 to 12 years, with depressive and obsessive
      compulsive disorders have been examined. Patients were treated with torin
      (sertraline) in dosage 25-50 mg daily during 4 weeks. Drug efficacy was evaluated
      using a children neurotic questionnaire and the Spilberger-Khanin anxiety scale.
      In the end of therapy, the complete reduction of obsessive and depressive
      symptoms was reached in 37,5% of patients, the improvement - in 51,9%. No side
      effects have been observed. The authors recommend torin for treatment of
      depression in children.

PMID- 20823826
TI  - [Efficacy of adepress (paroxetin) in generalized anxiety disorder].
AB  - The aim of the study was to evaluate efficacy of adepress (paroxetin) in
      different clinical variants of generalized anxiety disorder (GAD). Adepress was
      used as a monotherapy during 42 days. Patient's state was assessed using Hamilton
      anxiety scale (HAM-A) at baseline and every week thereafter. The study included
      49 patients aged 36,2+/-8,2 years. Patients were stratified into two groups
      according to the predominance of somatic (24 cases) or cognitive (21 cases)
      anxiety. The efficacy of adepress was shown both in a separate GAD and in a GAD
      with comorbid psychopathology. The effect of the drug was seen in patients with
      somatic anxiety after 3-4 weeks and in patients with cognitive anxiety after 3-6
      weeks.

PMID- 20823827
TI  - [S100B protein and autoantibodies to S100B protein in diagnostics of brain damage
      in craniocerebral trauma in children].
AB  - Levels of antibodies AB (AB) to S100B and S100B protein were studied in the blood
      serum of children with different severity and outcomes of traumatic brain injury
      (TBI) from the 1st to 15-75th days after TBI. Severity and outcomes were assessed
      using the Glasgow Coma Scale (GCS). Patients were stratified by outcomes into the
      following groups: complete recovery (group 1), moderate disability (group 2),
      high disability (group 3), vegetative state (group 4) and fatal outcome (group
      5). In patients of groups 1-3, the changes of S100B in the blood serum didn't
      depend on the severity of brain's damage; the significant increase of S100B
      protein levels in the 1st day was accompanied by the decrease to the normal range
      in the following 2-3 days. On the contrary, the levels of nAB in these groups
      increased starting from 3-5 days corresponding to the severity of brain's damage.
      The development of vegetative state was accompanied by low S100B and high AB to
      S100B levels in the blood serum. The maximal level of S100B protein and increased
      levels of AB were observed in patients with fatal outcome. In most patients with
      combined TBI, the levels of both parameters were higher compared to those with
      separate TBI.

PMID- 20823828
TI  - [Neurochemical markers of neurodegeneration in the early diagnosis of Alzheimer's
      disease, vascular and mixed dementia].
AB  - A study of 27 patients with dismnestic variant of moderate cognitive impairment
      (MCI) and 20 patients with neurodynamic-dysregulatory variant was carried out.
      The more intensive atrophic process supported by neuroimaging data and changed
      levels of neurodegeneration biomarkers - phosphorylated tau-protein 181 and beta
      amyloid 42 - were found in patients with dismnestic MCI variant. The follow-up
      study showed that the large number of patients with progressive cognitive
      disorders associated with conversion to dementia was observed in this group. In
      conclusion, the determination of the neurochemical markers in the cerebrospinal
      fluid allows to detect the neurodegenerative process at early stages of the
      disease and assists in detection of cases with increased risk of Alzheimer's
      disease.

PMID- 20823829
TI  - [Pathogenesis and new strategy in treatment of neuronal conductivity impairments
      in compression-ischemic neuropathies: a clinical and experimental study].
AB  - Compression-ischemic neuropathies remain one of the most actual problems of
      contemporary neurology due to the prevalence and commonly poor outcome. In the
      present work, we studied pathogenetic mechanisms of the formation and restoration
      of neural conductivity in the compression-ischemic model in rabbits and analyzed
      some features of therapeutic efficacy of the anticholinesterase drug neuromidin
      in clinical treatment of compression-ischemic neuropathies. We observed a
      generalized reaction of the nervous system to the acute limb compression in
      experimental animals. The ability of neuromidin to improve the central
      conductivity has been clearly shown. The results obtained allow recommending
      neuromidin in the treatment of patients with compression-ischemic neuropathies
      owing to its central and peripheral effects.

PMID- 20823830
TI  - [New evidence of the prion nature of amyotrophic leukospongiosis].
AB  - We described 2 cases and presented new experimental data on the study of the
      etiopathogenesis of amyotrophic leukospongiosis (AL) using Western blot,
      electronic and atomic force microscopy. AL is characterized by the gradual and
      steady progression of flaccid paralysis of extremities and muscles of the trunk
      without the expressed atrophy with an inevitable fatal outcome resulting in
      breathing disorders of spinal type, degenerative changes of the central nervous
      system and, first of all, spongiosis of the white matter of the brain. Several
      lines of evidence suggest that the accumulation of pathological prion protein
      (PrPAL) in the human brain is a critical event for the development of the
      disease. The new findings add knowledge of the AL etiopathogenesis and support
      the evidence that the disease is caused by prion infection and refers to the
      group of transmissible spongiform encephalopathies.

PMID- 20823831
TI  - Plant virus-mediated induction of miR168 is associated with repression of
      ARGONAUTE1 accumulation.
AB  - Virus infections induce the expression of ARGONAUTE1 (AGO1) mRNA and in parallel
      enhance the accumulation of miR168 (regulator of AGO1 mRNA). Here, we show that
      in virus-infected plants the enhanced expression of AGO1 mRNA is not accompanied
      by increased AGO1 protein accumulation. We also show that the induction of AGO1
      mRNA level is a part of the host defence reaction, whereas the induction of
      miR168, which overlaps spatially with virus-occupied sectors, is mediated mainly
      by the Tombusvirus p19 RNA-silencing suppressor. The absence of p19 results in
      the elimination of miR168 induction and accompanied with the enhanced
      accumulation of AGO1 protein. In transient expression study, p19 mediates the
      induction of miR168 and the down-regulation of endogenous AGO1 level. P19 is not
      able to efficiently bind miR168 in virus-infected plants, indicating that this
      activity is uncoupled from the small RNA-binding capacity of p19. Our results
      imply that plant viruses can inhibit the translational capacity of AGO1 mRNA by
      modulating the endogenous miR168 level to alleviate the anti-viral function of
      AGO1 protein.

PMID- 20823833
TI  - In-frame dystrophin following exon 51-skipping improves muscle pathology and
      function in the exon 52-deficient mdx mouse.
AB  - A promising therapeutic approach for Duchenne muscular dystrophy (DMD) is exon
      skipping using antisense oligonucleotides (AOs). In-frame deletions of the hinge
      3 region of the dystrophin protein, which is encoded by exons 50 and 51, are
      predicted to cause a variety of phenotypes. Here, we performed functional
      analyses of muscle in the exon 52-deleted mdx (mdx52) mouse, to predict the
      function of in-frame dystrophin following exon 51-skipping, which leads to a
      protein lacking most of hinge 3. A series of AOs based on phosphorodiamidate
      morpholino oligomers was screened by intramuscular injection into mdx52 mice. The
      highest splicing efficiency was generated by a two-oligonucleotide cocktail
      targeting both the 5' and 3' splice sites of exon 51. After a dose-escalation
      study, we systemically delivered this cocktail into mdx52 mice seven times at
      weekly intervals. This induced 20-30% of wild-type (WT) dystrophin expression
      levels in all muscles, and was accompanied by amelioration of the dystrophic
      pathology and improvement of skeletal muscle function. Because the structure of
      the restored in-frame dystrophin resembles human dystrophin following exon 51
      skipping, our results are encouraging for the ongoing clinical trials for DMD.
      Moreover, the therapeutic dose required can provide a suggestion of the
      theoretical equivalent dose for humans.

PMID- 20823832
TI  - Dishevelled, a Wnt signalling component, is involved in mitotic progression in
      cooperation with Plk1.
AB  - Wnt signalling is known to promote G1/S progression through the stimulation of
      gene expression, but whether this signalling regulates mitotic progression is not
      clear. Here, the function of dishevelled 2 (Dvl2), which transmits the Wnt
      signal, in mitosis was examined. Dvl2 localized to the spindles and spindle poles
      during mitosis. When cells were treated with nocodazole, Dvl2 was observed at the
      kinetochores (KTs). Dvl2 bound to and was phosphorylated at Thr206 by a mitotic
      kinase, Polo-like kinase 1 (Plk1), and this phosphorylation was required for
      spindle orientation and stable microtubule (MT)-KT attachment. Dvl2 was also
      found to be involved in the activation of a spindle assembly checkpoint (SAC)
      kinase, Mps1, and the recruitment of other SAC components, Bub1 and BubR1, to the
      KTs. However, the phosphorylation of Dvl2 by Plk1 was dispensable for SAC.
      Furthermore, Wnt receptors were involved in spindle orientation, but not in MT-KT
      attachment or SAC. These results suggested that Dvl2 is involved in mitotic
      progression by regulating the dynamics of MT plus-ends and the SAC in Plk1
      dependent and -independent manners.

PMID- 20823834
TI  - EUS-guided broad plexus neurolysis over the superior mesenteric artery using a 25
      gauge needle.
AB  - OBJECTIVES: Endoscopic ultrasonography (EUS)-guided celiac plexus neurolysis (EUS
      CPN) is safe and effective but not beneficial for some patients with extended
      abdominal cancer. We compared the effectiveness of standard EUS-CPN and EUS
      guided broad plexus neurolysis (EUS-BPN) that extends over the superior
      mesenteric artery (SMA) using a 25-gauge needle. METHODS: Consecutive patients
      referred to our quaternary EUS centers were eligible for inclusion. To evaluate
      the neurolytic spread, contrast was mixed with the neurolytic agent and post
      procedure computed tomography scanning was performed. The regions containing the
      celiac, superior, and inferior mesenteric arteries were divided on the frontal
      plane into six areas: upper right and left, middle right and left, and lower
      right and left. The number of contrast-bearing areas after EUS-CPN and EUS-BPN
      were related to the degree of pain relief achieved. RESULTS: A total of 67
      patients with advanced abdominal cancer were included (34 EUS-CPN and 33 EUS
      BPN). The qualitative variables of the two groups did not differ significantly.
      The EUS-BPN group had more patients with six contrast-bearing areas (42%) than
      the EUS-CPN group (0%). These patients had significantly better short-term and
      long-lasting pain relief than patients with less than five contrast-bearing
      areas. EUS-BPN patients exhibited significantly greater reductions in days 7 and
      30 visual analog pain scale scores than EUS-CPN patients. CONCLUSIONS: Our
      preliminary data suggested that EUS-BPN using a 25-gauge needle provides patients
      with advanced abdominal cancer with better pain relief than standard EUS-CPN, and
      without incurring serious complications. Moreover, it seems that broad neurolysis
      over the SMA may provide superior analgesia.

PMID- 20823835
TI  - Carcinoid tumors of the gastrointestinal tract: trends in incidence in England
      since 1971.
AB  - OBJECTIVES: The epidemiology of gastrointestinal neuroendocrine tumors (GI-NETs)
      is poorly understood. Recent analyses have suggested changes in the incidence and
      distribution of such tumors, but have generally used data sets containing small
      patient numbers. We aimed to define trends in the epidemiology of GI-NETs in
      England over a 36-year period. METHODS: We analyzed data from the national
      population-based cancer registry, which covers a population in excess of 50
      million, over the period 1971-2006. RESULTS: In all, 10,324 cases of GI-NETs were
      identified. The overall incidence increased from 0.27 (per 100,000 per year) to
      1.32 for men and from 0.35 to 1.33 for women. The anatomic distribution of tumors
      in the latest period analyzed was stomach 12%, small intestine 29%, appendix 38%,
      colon 13%, and rectum 8%. The largest absolute increase in incidence was seen in
      the appendix (from 0.03 to 0.41 in men; from 0.05 to 0.59 in women). The greatest
      relative increase was in gastric NETs, increasing 2,325% in men, and 4,746% in
      women. Overall, 48% of GI-NETs occurred in men. Sex-specific incidence rates for
      gastric, colonic, and rectal NETs are similar, whereas appendiceal lesions were
      more common in females, and small intestinal tumors in men. CONCLUSIONS: Large
      increases in the incidence of GI-NETs were observed, along with changes in
      anatomical distribution. Such changes may partly reflect changes in
      classification or improved detection through the increased use of endoscopy and
      imaging techniques. In view of the magnitude of these changes, particularly for
      gastric tumors, further studies to examine the underlying etiology of these
      changes are urgently indicated.

PMID- 20823836
TI  - Potential precipitating factors of esophageal variceal bleeding: a case-control
      study.
AB  - OBJECTIVES: Valsalva maneuver-associated activities such as straining during
      defecation, vomiting, and cough are believed to cause abrupt increase in variceal
      pressure. Whether these actions can precipitate rupture of esophageal varices
      (EV) is unknown. The association of EV bleeding with these activities and other
      potential risk factors such as ingestion of alcohol and non-steroidal anti
      inflammatory drugs was investigated. METHODS: Between January 2003 and May 2009,
      240 patients with liver cirrhosis and acute EV bleeding (group A) and 240 matched
      patients with Child-Pugh's class and moderate size EV without bleeding (group B)
      were included. Each patient was questioned regarding constipation, vomiting,
      cough, and other potential risk factors in the week prior to index bleeding
      (group A) or endoscopy (group B) using a standard questionnaire. RESULTS: Group A
      had more patients with constipation (n=44 vs. n=16, P<0.001) and higher
      constipation scores (0.79 +/- 1.67 vs. 0.25 +/- 0.92, P<0.001) than group B.
      Group A also had more patients with vomiting (n=60 vs. n=33, P=0.002) and higher
      vomiting scores (3.0 +/- 0.86 vs. 1.85 +/- 0.87, P<0.001). No difference in cough
      existed between the two groups (n=77 group A vs. n=73 group B); however, group A
      had higher cough scores (5.08 +/- 2.70 vs. 3.19 +/- 2.23, P<0.001). Group A had
      more patients with excessive alcohol consumption in the week preceding inclusion
      in the study (n=58 vs. n=5, P<0.001). On multivariate analysis, constipation
      score and vomiting score and alcohol consumption were independent determinants of
      first EV bleeding. CONCLUSIONS: Constipation, vomiting, severe coughing, and
      excessive consumption of alcohol may precipitate rupture of EV. A prospective
      cohort study is required to clarify the causal relationship between potential
      precipitating factors and EV bleeding.

PMID- 20823837
TI  - HLA-G 14 bp deletion/insertion polymorphism in celiac disease.
AB  - OBJECTIVES: Nonclassical major histocompatibility class I HLA-G antigen is a
      tolerogenic molecule that inhibits lytic activity of natural killer (NK) cells
      and cytotoxic T lymphocytes. Because of its immunomodulatory and tolerogenic
      properties, HLA-G molecules may have a role in celiac disease (CD). We analyzed
      the HLA-G 14 bp deletion/insertion polymorphism, known to have a functional
      effect on mRNA stability, in a group of 522 CD patients, stratified for the
      presence of HLA-DQ2 genotype, and 400 healthy individuals to evaluate the
      possible effect of the polymorphism on the risk to develop the disease. METHODS:
      HLA-G 14 bp deletion/insertion polymorphism (rs1704) was detected by polymerase
      chain reaction and double-checked by direct sequencing. RESULTS: The 14 bp
      inserted (I) allele and the homozygous I/I genotype were significantly more
      frequent in CD patients than in healthy controls. The presence of I allele was
      associated with an increased risk of CD (OR 1.35) and the effect of I allele was
      consistent with a recessive genetic model (P<0.001). CONCLUSIONS: Our results
      also indicate that the effect of the HLA-G D/I polymorphism is restricted for HLA
      DQ2, and not simply due to the presence of linkage disequilibrium with the major
      known risk factor; moreover we found that the presence of the I allele confers an
      increased risk of CD in addition to the risk conferred by HLA-DQ2 alone and that
      subjects that carry both DQ2 and HLA-G I alleles have an increased risk of CD
      than subjects that carry DQ2 but not the I allele.

PMID- 20823838
TI  - Prevalence and symptom pattern of pathologic esophageal acid reflux in patients
      with functional dyspepsia based on the Rome III criteria.
AB  - OBJECTIVES: To determine the prevalence and symptom pattern of pathologic
      esophageal acid reflux (PEAR) in patients with functional dyspepsia (FD) using
      the Rome III criteria, and to explore the value of a proton pump inhibitor (PPI)
      test in distinguishing the patients with and those without PEAR among FD
      patients. METHODS: Consecutive FD patients who fulfilled the Rome III criteria
      without predominant typical reflux symptoms (i.e., heartburn or regurgitation)
      were enrolled. All patients underwent upper endoscopy and an ambulatory 24-h pH
      monitoring. PEAR was defined as the percentage total time for which a pH value <4
      was >4.2% in the distal esophagus. Then, patients were treated with rabeprazole
      10 mg twice daily for 28 days. The symptom scores were measured by the frequency
      score multiplied by the severity scores of the predominant symptom before and at
      the end of the treatment, and the "PPI test" was defined as positive if the
      overall scores of the predominant dyspeptic symptom in the fourth week decreased
      by >50% compared with those of the baseline. RESULTS: One hundred eighty-six FD
      patients were enrolled, with predominant symptoms of epigastric pain (n=68),
      epigastric burning (n=47), bothersome postprandial fullness (n=54), and early
      satiation (n=17). The prevalence of PEAR was 31.7%, with the highest percentage
      (48.9%) in patients with epigastric burning as their predominant symptom. The
      prevalence of PEAR in patients with postprandial distress syndrome (PDS) and
      epigastric pain syndrome (EPS) were 36.6% (26/71) and 28.7% (33/115),
      respectively. Overall, 63.4% were positive for the "PPI test"; the rates were
      51.5, 85.0, 66.7, and 41.1% in patients with epigastric pain, epigastric burning,
      bothersome postprandial fullness, and early satiation as their predominant
      symptoms, respectively (chi(2)=17.59, P=0.001). The positive rates were 65.5 and
      60.6% in patients with PDS and EPS, respectively (chi(2)=0.41, P=0.522). The
      sensitivity and specificity of the "PPI test" in distinguishing FD patients with
      PEAR was 83.1 and 45.7%, respectively. CONCLUSIONS: PEAR is present in almost one
      third of FD patients; the prevalence is ~50% in those with epigastric burning.
      The "PPI test" has a limited value in distinguishing the FD patients with and
      those without PEAR.

PMID- 20823839
TI  - Increased risk of hospital admission for influenza in patients with celiac
      disease: a nationwide cohort study in Sweden.
AB  - OBJECTIVES: Although earlier studies suggest an increased risk of infectious
      disease in celiac disease (CD), data on the risk of influenza in patients with CD
      are limited. We examined the risk of hospital admission for influenza in CD
      patients, but for comparative reasons also in individuals with small-intestinal
      inflammation or normal mucosa but positive CD serology. METHODS: In 2006-2008, we
      collected duodenal/jejunal biopsy data on CD (Marsh 3: villous atrophy, VA;
      n=29,008 unique individuals) and inflammation (Marsh 1-2; n=13,200) from all 28
      pathology departments in Sweden. A third regional cohort consisted of 3,709
      individuals with positive CD serology but normal mucosa (Marsh 0). The biopsies
      were performed between 1969 and 2008. Through linkage with the Swedish Hospital
      Discharge Register, we estimated the risk of hospital admission for influenza
      compared with that of 224,114 age- and sex-matched controls from the general
      population. RESULTS: Individuals with CD were at increased risk of hospital
      admission for influenza (hazard ratio (HR)=2.1; 95% confidence interval (CI)=1.6
      2.7; n=81). The absolute risk of influenza was 30/100,000 person-years (excess
      risk: 16/100,000 person-years). Furthermore, children with CD were at increased
      risk of influenza (HR=2.5; 95% CI=1.3-4.8). Whereas individuals with inflammation
      without VA were also at increased risk of influenza (HR=1.9; 95% CI=1.4-2.5),
      individuals with normal mucosa but positive CD serology were not (HR=1.2; 95%
      CI=0.5-3.0). CONCLUSIONS: This study found an increased risk of hospital
      admission for influenza in patients with CD.

PMID- 20823841
TI  - Trends in social inequalities in male mortality, 2001-08. Intercensal estimates
      for England and Wales.
AB  - BACKGROUND: This article presents estimates of mortality rates for men of working
      age by the National Statistics Socio-economic Classification (NS-SEC). Previously
      it has been possible to produce such mortality rates only at the time of a
      census, when populations are enumerated by occupation and NS-SEC. This is the
      first time that annual intercensal estimates have been produced, enabling the
      measurement of health inequalities by NS-SEC for the period 2001-08. METHODS: The
      Labour Force Survey (LFS) was used to provide population denominators by age and
      NS-SEC for men aged 25-64 for each year between 2001 and 2008. Numbers of deaths
      for the corresponding period were obtained from death registrations, and age
      standardised mortality rates were derived. A number of measures of the inequality
      in mortality rates across socio-economic classes were compared. RESULTS: There
      has been a steady decrease in mortality rates for all NS-SEC classes over the
      period, 2001-08. Mortality rates for the 'Routine' class declined on average by
      around 11 deaths per 100,000 population per year, almost double that of the
      'Higher managerial and professional' class. Absolute differences between the
      mortality of the least and most advantaged classes showed a small decline based
      on three different measures. Relative differences, however, increased over this
      period. In 2001 the mortality rate of those in routine and manual occupations was
      2.0 times that of those in managerial and professional occupations. In 2008 that
      ratio had risen to 2.3. This pattern of declining absolute but rising relative
      inequalities is a well known phenomenon in the context of declining overall
      mortality rates. CONCLUSIONS: The results presented suggest that annual trends in
      inequalities in mortality at the national level can be effectively monitored
      using LFS-based measures. This would complement the current measures that are
      based on area of residence rather than the socio-economic position of the
      individual.

PMID- 20823842
TI  - Life expectancy and disability-free life expectancy estimates for Middle Super
      Output Areas; England, 1999-2003.
AB  - BACKGROUND: In recent years, there has been increasing demand for health
      indicators at small area level to support monitoring and planning. This study
      investigates the use of a small area geography, Middle Layer Super Output Areas
      (MSOAs) for the estimation and comparison of disability-free life expectancy
      (DFLE) in England. METHODS: Using death registrations from 1999 to 2003 and data
      on limiting long-term illness from the Census 2001, life expectancy and DFLE are
      estimated for English MSOAs and Government Office Regions. Figures are presented
      for quintiles based on MSOA DFLE values, and quintiles of relative deprivation
      using the Index of Multiple Deprivation 2004. Health inequalities are assessed at
      regional level and between quintile extremes for both measures. RESULTS: The
      distribution of DFLE across MSOAs was characterised by a north-south geographical
      divide: the highest DFLE at birth for males was in Kensington and Chelsea 016
      (73.9 years) and lowest was in Manchester 013 (44.1 years). For females the
      highest value was in Kensington and Chelsea 012 (74.4 years) and the lowest in
      Liverpool 039 (48.2 years). Over 40 per cent of MSOAs in the South East, but only
      about 3 per cent of those in the North East, were in the quintile with the
      highest DFLE values at birth. Conversely, the equivalent proportions in the
      quintile with the lowest values were approximately 4 per cent and 50 per cent
      respectively.At birth, males in the most affluent areas could expect to spend an
      additional 12.6 years without a disability compared to those in the most deprived
      areas. For females this inequality was 10.9 years. At age 65 inequalities
      persisted but the differences were narrower. CONCLUSIONS: This is the first use
      of MSOAs in estimating DFLE, and the results highlight the substantial
      inequalities between quintile groupings based on DFLE values as well as between
      the least and most deprived MSOAs in England. These findings provide useful
      health outcomes information to planners at the local level, for benchmarking
      purposes and to assist in resource allocation through the identification of
      differences in relative need between local populations.

PMID- 20823843
TI  - Amenable mortality as an indicator of healthcare quality - a literature review.
AB  - BACKGROUND: In 2008, the Office for National Statistics (ONS) suggested that
      research should be undertaken into whether amenable mortality - deaths considered
      avoidable due to medical intervention - could be used as an indicator of
      healthcare quality. The aim of this paper is to review the literature on amenable
      mortality in order to determine the extent to which the observed fall in amenable
      mortality is due to the healthcare system. METHODS: The literature reviewed
      covers mainly the Organisation for Economic Co-operation and Development (OECD)
      countries and can be broadly categorised into: (a) trends across OECD countries
      (b) pooled time series cross-country analyses of OECD countries and (c) cross
      section or time series analyses within countries. RESULTS: There is no consensus
      in the literature on exactly what constitutes amenable mortality, thereby making
      the concept in itself imprecise. However, there has been a fall in amenable
      mortality in the past few decades in most OECD countries including the UK. Since
      the fall in amenable mortality has been at a faster rate than that of
      'unavoidable' mortality, some studies have directly attributed this to the
      healthcare system. Others have tested the relationship between healthcare
      outcomes and healthcare inputs to determine the magnitude and direction of the
      relationship. No study has explicitly used a healthcare activity or quality
      variable in their analyses. This implies that the evidence that amenable
      mortality is an indicator of healthcare quality is far from overwhelming or
      clear. CONCLUSIONS: At this stage, it is premature to use amenable mortality in
      ONS's healthcare output calculations. We welcome comments from those interested
      in this field, and suggestions to improve understanding in this area.

PMID- 20823844
TI  - Computational reconstruction of tissue-specific metabolic models: application to
      human liver metabolism.
AB  - The computational study of human metabolism has been advanced with the advent of
      the first generic (non-tissue specific) stoichiometric model of human metabolism.
      In this study, we present a new algorithm for rapid reconstruction of tissue
      specific genome-scale models of human metabolism. The algorithm generates a
      tissue-specific model from the generic human model by integrating a variety of
      tissue-specific molecular data sources, including literature-based knowledge,
      transcriptomic, proteomic, metabolomic and phenotypic data. Applying the
      algorithm, we constructed the first genome-scale stoichiometric model of hepatic
      metabolism. The model is verified using standard cross-validation procedures, and
      through its ability to carry out hepatic metabolic functions. The model's flux
      predictions correlate with flux measurements across a variety of hormonal and
      dietary conditions, and improve upon the predictive performance obtained using
      the original, generic human model (prediction accuracy of 0.67 versus 0.46).
      Finally, the model better predicts biomarker changes in genetic metabolic
      disorders than the generic human model (accuracy of 0.67 versus 0.59). The
      approach presented can be used to construct other human tissue-specific models,
      and be applied to other organisms.

PMID- 20823845
TI  - Emergent cooperation in microbial metabolism.
AB  - Mixed microbial communities exhibit emergent biochemical properties not found in
      clonal monocultures. We report a new type of synthetic genetic interaction,
      synthetic mutualism in trans (SMIT), in which certain pairs of auxotrophic
      Escherichia coli mutants complement one another's growth by cross-feeding
      essential metabolites. We find significant metabolic synergy in 17% of 1035 such
      pairs tested, with SMIT partners identified throughout the metabolic network.
      Cooperative phenotypes show more growth on average by aiding the proliferation of
      their conjugate partner, thereby expanding the source of their own essential
      metabolites. We construct a quantitative, predictive, framework for describing
      SMIT interactions as governed by stoichiometric models of the metabolic networks
      of the interacting strains.

PMID- 20823847
TI  - Towards whole-body systems physiology.

PMID- 20823848
TI  - From bench to website.

PMID- 20823846
TI  - Reconstruction and flux-balance analysis of the Plasmodium falciparum metabolic
      network.
AB  - Genome-scale metabolic reconstructions can serve as important tools for
      hypothesis generation and high-throughput data integration. Here, we present a
      metabolic network reconstruction and flux-balance analysis (FBA) of Plasmodium
      falciparum, the primary agent of malaria. The compartmentalized metabolic network
      accounts for 1001 reactions and 616 metabolites. Enzyme-gene associations were
      established for 366 genes and 75% of all enzymatic reactions. Compared with other
      microbes, the P. falciparum metabolic network contains a relatively high number
      of essential genes, suggesting little redundancy of the parasite metabolism. The
      model was able to reproduce phenotypes of experimental gene knockout and drug
      inhibition assays with up to 90% accuracy. Moreover, using constraints based on
      gene-expression data, the model was able to predict the direction of
      concentration changes for external metabolites with 70% accuracy. Using FBA of
      the reconstructed network, we identified 40 enzymatic drug targets (i.e. in
      silico essential genes), with no or very low sequence identity to human proteins.
      To demonstrate that the model can be used to make clinically relevant
      predictions, we experimentally tested one of the identified drug targets,
      nicotinate mononucleotide adenylyltransferase, using a recently discovered small
      molecule inhibitor.

PMID- 20823849
TI  - HepatoNet1: a comprehensive metabolic reconstruction of the human hepatocyte for
      the analysis of liver physiology.
AB  - We present HepatoNet1, the first reconstruction of a comprehensive metabolic
      network of the human hepatocyte that is shown to accomplish a large canon of
      known metabolic liver functions. The network comprises 777 metabolites in six
      intracellular and two extracellular compartments and 2539 reactions, including
      1466 transport reactions. It is based on the manual evaluation of >1500 original
      scientific research publications to warrant a high-quality evidence-based model.
      The final network is the result of an iterative process of data compilation and
      rigorous computational testing of network functionality by means of constraint
      based modeling techniques. Taking the hepatic detoxification of ammonia as an
      example, we show how the availability of nutrients and oxygen may modulate the
      interplay of various metabolic pathways to allow an efficient response of the
      liver to perturbations of the homeostasis of blood compounds.

PMID- 20823851
TI  - An experiment in progress.

PMID- 20823852
TI  - Lack of uptake threatens promise of HIV vaccines.

PMID- 20823853
TI  - Line item cut threatens monitoring of more than West Nile virus.

PMID- 20823850
TI  - Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant
      melanoma.
AB  - B-RAF is the most frequently mutated protein kinase in human cancers. The finding
      that oncogenic mutations in BRAF are common in melanoma, followed by the
      demonstration that these tumours are dependent on the RAF/MEK/ERK pathway,
      offered hope that inhibition of B-RAF kinase activity could benefit melanoma
      patients. Herein, we describe the structure-guided discovery of PLX4032 (RG7204),
      a potent inhibitor of oncogenic B-RAF kinase activity. Preclinical experiments
      demonstrated that PLX4032 selectively blocked the RAF/MEK/ERK pathway in BRAF
      mutant cells and caused regression of BRAF mutant xenografts. Toxicology studies
      confirmed a wide safety margin consistent with the high degree of selectivity,
      enabling Phase 1 clinical trials using a crystalline formulation of PLX4032 (ref.
      5). In a subset of melanoma patients, pathway inhibition was monitored in paired
      biopsy specimens collected before treatment initiation and following two weeks of
      treatment. This analysis revealed substantial inhibition of ERK phosphorylation,
      yet clinical evaluation did not show tumour regressions. At higher drug exposures
      afforded by a new amorphous drug formulation, greater than 80% inhibition of ERK
      phosphorylation in the tumours of patients correlated with clinical response.
      Indeed, the Phase 1 clinical data revealed a remarkably high 81% response rate in
      metastatic melanoma patients treated at an oral dose of 960 mg twice daily. These
      data demonstrate that BRAF-mutant melanomas are highly dependent on B-RAF kinase
      activity.

PMID- 20823854
TI  - China to scale up collaborations in infectious disease research.

PMID- 20823855
TI  - Theory is acid test for fructose's blood pressure role.

PMID- 20823856
TI  - Price of misconduct probes can surpass $500,000.

PMID- 20823857
TI  - Amidst growing vaccine concerns, NIH sets up engine for answers.

PMID- 20823859
TI  - Straight talk with ... Rajiv Shah. Interview by Elie Dolgin.

PMID- 20823861
TI  - Fresh as a daisy: Alexandra Daisy Ginsberg.

PMID- 20823862
TI  - Selling point: David Goodsell.

PMID- 20823863
TI  - Revitalizing design: Revital Cohen.

PMID- 20823864
TI  - Silence is golden: Phil Gamblen and Guy Ben-Ary.

PMID- 20823866
TI  - The real war on drugs.

PMID- 20823867
TI  - Personalized investigation.

PMID- 20823868
TI  - Masterminds behind pharmaceutical fraud deserve prison time.

PMID- 20823870
TI  - Pericyte constriction after stroke: the jury is still out.

PMID- 20823871
TI  - Being too inclusive about synuclein inclusions.

PMID- 20823873
TI  - Sodium guidelines should be taken with a grain of salt.

PMID- 20823875
TI  - A cancer fate in the hands of a samurai.

PMID- 20823876
TI  - Thyroid hormones: igniting brown fat via the brain.

PMID- 20823877
TI  - NET loss of air in cystic fibrosis.

PMID- 20823878
TI  - Cocaine sobers up.

PMID- 20823880
TI  - Finding the tumor copycat. Therapy fails, patients don't.

PMID- 20823881
TI  - Finding the tumor copycat: approximating a human cancer.

PMID- 20823883
TI  - The 2010 scientific strategic plan of the Global HIV Vaccine Enterprise.

PMID- 20823884
TI  - Phase I and pharmacological study of the broad-spectrum tyrosine kinase inhibitor
      JNJ-26483327 in patients with advanced solid tumours.
AB  - BACKGROUND: JNJ-26483327 is an oral, potent, multi-targeted tyrosine kinase
      inhibitor, inhibiting kinases of epidermal growth factor receptor (EGFR)-1, -2
      and -4, rearranged during transfection (RET) receptor, vascular endothelial
      growth factor receptor (VEGFR)-3 and Src family (Lyn, Fyn, Yes) at low nanomolar
      concentrations. This phase I, accelerated titration study assessed maximum
      tolerated dose, safety, pharmacokinetics and pharmacodynamic effects of JNJ
      26483327. METHODS: Nineteen patients with advanced cancers received JNJ-26483327
      continuous twice daily (BID) in escalating dose cohorts ranging from 100 to 2100
      mg. Pharmacodynamic effects were assessed in paired skin biopsies and blood.
      RESULTS: JNJ-26483327 was well tolerated in doses up to 1500 mg BID, with target
      inhibition-related toxicity such as diarrhoea and skin rash, and other common
      reported toxicities being nausea, vomiting, anorexia and fatigue. At 2100 mg, two
      episodes of dose-limiting toxicity were observed, consisting of grade 3 anorexia
      and a combination of grade 3 anorexia and fatigue, respectively. Pharmacokinetics
      were dose proportional up to 1500 mg in which plasma levels were obtained showing
      anti-tumour activity in xenograft mouse models. Pharmacodynamic analysis did not
      show a substantial effect on expression of Ki-67, p27(kip1), phosphorylated
      mitogen-activated protein kinase, phosphorylated Akt and EGFR, and serum levels
      of sVEGFR-2, VEGF-C and VEGF-D remained unchanged. Stable disease was noted in
      six patients (32%). CONCLUSION: JNJ-26483327 is well tolerated and shows a
      predictable pharmacokinetic profile; the recommended dose for further studies is
      1500 mg BID.

PMID- 20823885
TI  - Carcinoma in situ testis displays permissive chromatin modifications similar to
      immature foetal germ cells.
AB  - BACKGROUND: The majority of testicular germ cell cancers develop through a pre
      invasive carcinoma in situ (CIS) stage. The CIS cell is a neoplastic counterpart
      of foetal germ cells. During their development, foetal germ cells undergo
      extensive and essential epigenetic modifications, but little is known about
      epigenetic patterns in CIS cells. METHODS: Immunohistochemistry was used to
      investigate epigenetic patterns in CIS, germ cell tumours, normal adult and
      foetal testicular tissue. RESULTS: CIS cells show low levels of DNA methylation
      and repressive histone modifications H3K9me2 and H3K27me3, but high levels of
      H3K9 acetylation, H3K4 methylation and H2A.Z, which all are associated with an
      activated and accessible chromatin structure. Collectively this renders a
      permissive chromatin structure and in accordance high levels of RNA polymerase II
      activity and proliferation (Ki-67 and mitotic index) is observed in CIS cells.
      Epigenetic patterns similar to that of CIS cells were observed in human gonocytes
      present within sex cords in foetal testes but correspond to migrating primordial
      germ cell in mice. Development of overt tumours involves epigenetic repression of
      the chromatin. CONCLUSION: CIS cells have a permissive and foetal-like chromatin
      structure, which is associated with a high transcriptional and proliferative
      activity, likely empowering neoplastic transformation. Developmental epigenetic
      cues in foetal germ cells are substantially different between humans and mice.

PMID- 20823886
TI  - Estimation and external validation of a new prognostic model for predicting
      recurrence-free survival for early breast cancer patients in the UK.
AB  - BACKGROUND: We aimed to estimate and externally validate a new UK-specific
      prognostic model for predicting the long-term risk of a first recurrent event
      (local recurrence, metastatic recurrence, or second primary breast cancer) in
      women diagnosed with early breast cancer. METHODS: Using data on the prognostic
      characteristics and outcomes of 1844 women treated for early breast cancer at the
      Churchill Hospital in Oxford, parametric regression-based survival analysis was
      used to estimate a prognostic model for recurrence-free survival. The model,
      which incorporated established prognostic factors, was externally validated using
      independent data. Its performance was compared with that of the Nottingham
      Prognostic Index (NPI) and Adjuvant! Online. RESULTS: The number of positive
      axillary lymph nodes, tumour grade, tumour size and patient age were strong
      predictors of recurrence. Oestrogen receptor (ER) positivity was shown to afford
      a moderate protective effect. The model was able to separate patients into
      distinct prognostic groups, and predicted well at the patient level, mean Brier
      Accuracy Score=0.17 (s.e.=0.004) and overall C=0.745 (95% CI, 0.717-0.773). Its
      performance diminished only slightly when applied to a second independent data
      set. When compared with the NPI, the model was able to better discriminate
      between women with excellent and good prognoses, and it did not overestimate 10
      year recurrence-free survival to the extent observed for Adjuvant! Online.
      CONCLUSION: The model estimated here predicts well at both the individual patient
      and group levels, and appears transportable to patients treated at other UK
      hospitals. Its parametric form permits long-term extrapolation giving it an
      advantage over other prognostic tools currently in use. A simple point scoring
      system and reference table allow 5-, 10-, and 15-year predictions from the model
      to be quickly and easily estimated. The model is also available to download as an
      interactive computer program.

PMID- 20823887
TI  - Loss of tumoral expression of soluble IL-6 receptor is associated with disease
      progression in colorectal cancer.
AB  - BACKGROUND: Interleukin-6 (IL-6) binds both the membrane and soluble forms of the
      IL-6 receptor (sIL-6R), which induces a complex with gp130, and proliferation of
      tumour cells. The aim of this study is to clarify the relationship between
      tumoral sIL-6R expression and disease progression in colorectal cancer patients.
      METHODS: We measured tissue concentrations of sIL-6R in tumour and normal mucosa
      from 161 colorectal cancer patients undergoing surgery, and in supernatants from
      colon cancer cell lines. The expression of IL-6, IL-6R and gp130 was evaluated by
      immunohistochemical analysis. RESULTS: Loss of tumour expression of sIL-6R as
      defined by sIL-6R Ca/N ratio <1.0 was significantly associated with factors
      reflecting disease progression, and was an independent prognostic factor not only
      in all the patients in this study, but also in the patients with curative intent.
      Colon cancer cell lines produced sIL-6R in vitro, and the production of sIL-6R in
      cancer cell lines was stimulated by cytokine stimulation. Immunohistochemistry
      revealed that loss of tumour expression of sIL-6R was significantly inversely
      correlated with intense IL-6 expression in the cytoplasm of cancer cells. In
      addition, tumoral IL-1beta expression was significantly correlated with sIL-6R
      expression. CONCLUSION: Loss of tumour expression of sIL-6R is associated with
      colorectal cancer disease progression.

PMID- 20823888
TI  - Safety and efficacy of the combination of erlotinib and sirolimus for the
      treatment of metastatic renal cell carcinoma after failure of sunitinib or
      sorafenib.
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) is an important therapeutic
      target in the treatment of renal cell carcinoma (RCC). Pre-clinical data indicate
      that the combined inhibition of both the epidermal growth factor receptor and
      mTOR results in enhanced anticancer activity. METHODS: All patients had
      metastatic RCC with progression after treatment with sunitinib and/or sorafenib.
      Treatment consisted of erlotinib 150 mg orally once a day starting on day 1 and
      sirolimus 6 mg orally on day 8 followed by 2 mg daily, adjusted according to
      blood levels. RESULTS: A total of 25 patients were enrolled between July 2006 and
      March 2008. The median progression-free survival (PFS) was 12 weeks (95% CI 5.9
      18.1) and median overall survival (OS) 40 weeks (95% CI 0-85.7). No confirmed
      complete or partial responses were observed, but stable disease >6 months was
      noted in 21.8% (95% CI 4.9-38.6) of patients. The most common adverse events were
      rash and diarrhoea. There was no correlation between erlotinib, OSI-420 (days 8
      and 15) or sirolimus (days 15 and 29) blood levels and PFS or OS. CONCLUSIONS:
      The combination of sirolimus and erlotinib for RCC failed to demonstrate an
      advantage over available single-agent therapy in the second-line setting.

PMID- 20823889
TI  - Osteopontin is a marker for cancer aggressiveness and patient survival.
AB  - BACKGROUND: Only a fraction of molecular cancer markers identified in the
      scientific literature have found clinical use. Specifically, few predictors of
      invasiveness are established in diagnostics. Meta-analysis is a valuable tool for
      biomarker validation. Here, we evaluate Osteopontin as a marker for tumor
      aggressiveness (grade, stage, early progression) and patient survival. METHODS:
      Publications through 2008 with the keywords 'osteopontin AND cancer' were
      retrieved. Titles and abstracts were screened for studies presenting original
      data on human subjects. This left 228 publications for data extraction. We
      applied categorical data analysis for testing the relationship between
      Osteopontin and a clinical variable. RESULTS: Osteopontin ranks correlated with
      lower overall and disease-free/relapse-free survival in all tumors combined, as
      well as in lung cancer, breast cancer, prostate cancer, head and neck cancer, and
      liver cancer. Further, Osteopontin levels correlated with tumor grade and stage
      for all tumors combined and for several individual tumor types. Osteopontin
      levels were significantly associated with the early progression of eight cancers,
      independent in one, and inversely correlated in two. CONCLUSIONS: Osteopontin is
      significantly associated with survival in several forms of cancer. Osteopontin
      levels are also markers for stage, grade, and early tumor progression in multiple
      cancers, reflecting a common molecular underpinning for distinct clinical
      measures. Osteopontin has value as a clinical tumor progression marker.

PMID- 20823893
TI  - 1H,1'H-[3,3']biindolyl from the terrestrial fungus Gliocladium catenulatum.

PMID- 20823894
TI  - Macrolides of the bafilomycin family produced by Streptomyces sp. CS.
AB  - Five new 16-membered macrolides (1-5), belonging to the bafilomycin subfamily,
      were isolated from the fermentation broth of Streptomyces sp. CS, a commensal
      microbe of Maytenus hookeri. Their structures including relative configurations
      were elucidated based on NMR data and analysis of single crystal X-ray
      diffraction data. The cytotoxicities of compounds 1-5 on the MDA-MB-435 cell line
      were analyzed by the MTT method and the IC(50) values were found to be 4.2, 4.5,
      5.5, 3.8 and 11.4 MUM, respectively.

PMID- 20823895
TI  - Effects of different doses of oral cholecalciferol on serum 25(OH)D, PTH, calcium
      and bone markers during fall and winter in schoolchildren.
AB  - BACKGROUND/OBJECTIVES: Controversies surround the actual requirements of vitamin
      D in adolescents. We aimed to assess the efficacy and safety of different doses
      of vitamin D in high schoolchildren of Taleghan (latitude 36.5 degrees N) near
      Tehran. SUBJECTS/METHODS: In a randomized double-blind, placebo-controlled trial,
      210 subjects, aged 14-20 years, 105 boys and 105 girls were assigned to three
      groups; group A (n=70) received 50 000 U oral cholecalciferol monthly (equal to
      1600 U per day), group B (n=70), 50 000 U bimonthly (equal to 800 U/day) and
      group C (n=70), placebo. The study began in November 2007 and continued until
      April 2008. Serum 25(OH)D, parathyroid hormone (PTH), calcium (Ca) and bone
      markers were measured. RESULTS: At baseline, girls had significantly lower
      concentrations of 25(OH)D than boys (19.25+/-16 vs 40.5+/-14 nmol/l). Mean
      25(OH)D increased from 32+/-22 to 60+/-27.5 and 28.25+/-14.5 to 45.75+/-24 in
      groups A and B, respectively (P<0.001); however, it did not change over time in
      group C (29+/-18 vs 29+/-17.5). Increment of mean 25(OH)D was higher in group A
      than in group B (P<0.01). In all groups, girls had lower concentrations of
      25(OH)D than boys (P<0.001). Serum Ca increased and PTH decreased in groups A and
      B (P<0.001). In group A, osteocalcin (OC) and bone-specific alkaline phosphatase
      increased (P<0.001), but in group B only OC increased (P<0.001). Urine C
      telopeptide and Ca did not change in all three groups; no case of hypercalcemia
      was observed. CONCLUSIONS: Although monthly administration of 50 000 U vitamin
      D(3) increased serum 25(OH)D significantly, it was apparently not enough to
      correct vitamin D deficiency, especially in girls.

PMID- 20823896
TI  - High serum 25-hydroxyvitamin D concentrations are associated with a favorable
      serum lipid profile.
AB  - BACKGROUND/OBJECTIVES: Low serum 25-hydroxyvitamin D (25(OH)D) concentrations are
      related to increased mortality. One possible explanation could be an association
      between serum 25(OH)D and serum lipids. SUBJECTS/METHODS: The study was performed
      at the University of Tromso, Northern Norway. In total, 8018 nonsmoking and 2087
      smoking subjects were included in a cross-sectional study performed in 2008, and
      1762 nonsmoking and 397 smoking subjects in a longitudinal study from 1994/1995
      to 2008. Nonfasting serum 25(OH)D, total cholesterol (TC), high-density
      lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), LDL
      C/HDL-C ratio and triacylglycerol (TAG) were measured. RESULTS: After adjustment
      for gender, age, sample month and body mass index in the cross-sectional study,
      there was a significant increase in serum TC, HDL-C and LDL-C, and a significant
      decrease in serum LDL-C/HDL-C ratio and TAG across increasing serum 25(OH)D
      quartiles. For serum HDL-C and TAG in nonsmokers the differences between the
      means for the highest and lowest serum 25(OH)D quartiles were 6.0 and 18.5%,
      respectively. In the longitudinal study, an increase in serum 25(OH)D was
      associated with a significant decrease in serum TAG. CONCLUSIONS: There is a
      cross-sectional association between serum 25(OH)D and serum lipids, and a
      longitudinal association over 14 years between serum 25(OH)D and TAG, which may
      contribute to explain the relation between low serum 25(OH)D concentrations and
      mortality.

PMID- 20823897
TI  - The effect of folinic acid supplementation on homocysteine concentrations in
      newborns.
AB  - OBJECTIVE: The incidence of cerebrovascular accidents (CVA) occurring perinatally
      is relatively high and aspects of the multifactorial pathophysiology remain
      unclear. Elevated homocysteine concentrations have been shown to be associated
      with an increased risk for CVA in children and even in newborns. We studied the
      possible homocysteine lowering effect of folinic acid in newborns. METHOD: We
      included 37 newborns in our prospective randomized folinic acid (given as 5
      formyltetrahydrofolate) intervention study from patients admitted to our neonatal
      intensive care unit (18 controls, 19 intervention group). We measured total
      homocysteine (tHcy) and plasma folate concentrations at three time points
      (baseline, 1 and 2 weeks after intervention). The intervention group was treated
      with folinic acid (70 MUg/kg/day) for 2 weeks. We calculated median
      concentrations (25th and 75th percentiles). RESULTS: Median tHcy concentrations
      at the three time points did not differ from each other in the control group nor
      in the intervention group. We also could not observe different tHcy
      concentrations between both groups. Plasma folate concentrations increased in the
      intervention group (mean increase 167% (95% confidence interval (CI) -291, 625))
      compared with control group (mean increase -12% (95% CI -132, 108)), P for
      treatment effect: 0.03. CONCLUSION: We could not demonstrate a homocysteine
      lowering effect of folinic acid administration in newborns. This indicates that
      one carbon metabolism in newborns differs form adults. Cobalamin might be a
      better strategy to lower tHcy concentrations in newborns.

PMID- 20823898
TI  - Postprandial hyperglycemia and insulin response are affected by sea buckthorn
      (Hippophae rhamnoides ssp. turkestanica) berry and its ethanol-soluble
      metabolites.
AB  - BACKGROUND/OBJECTIVES: Repeated postprandial hyperglycemia and subsequent mild,
      late hypoglycemia as well as high postprandial insulin response lead to metabolic
      events that may eventually develop into type 2 diabetes. The aim of this study
      was to assess how sea buckthorn berries as well as two sea buckthorn extraction
      residues modulate the postprandial metabolism after a high-glucose meal.
      SUBJECTS/METHODS: Ten healthy normal-weight male volunteers consumed four study
      breakfasts, one control (A) and three sea buckthorn meals on four distinct study
      days. All the meals contained yoghurt and glucose (50 g). The sea buckthorn
      ingredients used were dried and crushed whole berries (meal B1), supercritical
      fluid (SF)-carbon dioxide (CO(2))-extracted oil-free berries (meal B2) or ethanol
      extracted SF-CO(2)-extraction residue (meal B3). Blood samples for glucose,
      insulin and tumor necrosis factor-alpha analyses were collected before and during
      the 6-h study period. RESULTS: Meal B1 suppressed the postprandial peak insulin
      response when compared with meal A (Deltaconcentration of 30-min peak value--21.8
      mU/l, P=0.039), and stabilized postprandial hyperglycemia and subsequent
      hypoglycemia (Deltaconcentration of 30-min peak value--120-min value -30.4 mU/l,
      P=0.036). Furthermore, meal B2 resulted in a more stable insulin response than
      the control meal (Deltaconcentration of 30-min peak value--120-min value -25.9
      mU/l, P=0.037). CONCLUSIONS: Removal of the CO(2)-soluble oil component from the
      berries did not show a significant change in the studied postprandial effects of
      the berries. The EtOH soluble components, again showed advantageous properties in
      both insulin and glucose responses.

PMID- 20823899
TI  - Consumption of rapeseed honey leads to higher serum fructose levels compared with
      analogue glucose/fructose solutions.
AB  - BACKGROUND: Studies suggest that honey has less influence on serum glucose
      concentrations than monosaccharides and disaccharides. Previous studies, however,
      have only analysed glucose metabolism. METHODS: This study investigated the
      influence of two types of honey (rapeseed and acacia) on the serum levels of
      glucose, fructose, insulin and C-peptide values in healthy subjects. The results
      were compared with honey-comparable glucose-fructose solutions. All solutions
      contained 75 g of glucose and/or fructose. RESULTS: We found significantly higher
      fructose serum levels with rapeseed honey after 2 h but no such differences for
      acacia honey. C-peptide levels were significantly higher after administration of
      both honeys after 1 and 2 h. CONCLUSIONS: For the first time it has been found
      out that honey ingestion leads to a rise of blood fructose concentration: in one
      case, this rise was lower than that achieved after fructose/glucose controls, in
      the other cases it was same as after the controls. Fructose metabolism may be
      inhibited by unidentified substances present in the rapeseed honey. Further study
      to elucidate underlying mechanisms may be worthwhile, as usually there is no
      differentiation between the different types of honey.

PMID- 20823900
TI  - Risk associations of obesity with sugar-sweetened beverages and lifestyle factors
      in Chinese: the 'Better Health for Better Hong Kong' health promotion campaign.
AB  - BACKGROUND/OBJECTIVES: Excessive consumption of sugar-sweetened beverages (SSBs)
      increases risk of obesity. Similar data are lacking in Chinese populations with
      rapid nutritional transition. We aimed to examine the association between SSB
      intake, lifestyle factors and obesity in Hong Kong Chinese. SUBJECTS/METHODS:
      This is a cross-sectional survey on SSB intake with 2295 (49.6%) men and 2334
      (50.4%) women (age: median 43.0 years, range 18-81 years). They were recruited
      from a territory-wide health promotion campaign in Hong Kong. All subjects
      completed a questionnaire and underwent simple health tests. Their SSB intake was
      based on a 1-week recall (1 unit of SSB=250 ml, frequent SSB consumption=daily
      intake >=2 units). RESULTS: Men were more likely than women to smoke, drink
      alcohol, frequently consumed SSB (20.5 vs 9.5%) and ate more meat portions
      (2.32+/-0.57 vs 2.15+/-0.44) but were physically more active (no exercise: 31.2
      vs 39.2%) (P-values: all <0.001). After adjusting for confounding factors,
      frequent SSB intake remained independently associated with obesity in women (odds
      ratio (95% confidence interval): 1.86 (1.36-2.55)) while physical inactivity
      (1.84 (1.41-2.39) for none vs regular), smoking (1.29 (1.05-1.58)) and high daily
      meat intake (2.15 (1.36, 3.42)) predicted obesity in men. CONCLUSIONS: In Chinese
      of working age, SSB consumption in women and physical inactivity, smoking and
      high meat intake in men were associated with obesity.

PMID- 20823901
TI  - Dietary trans fatty acid intake and maternal and infant adiposity.
AB  - BACKGROUND/OBJECTIVES: The fatty acid composition in maternal diet and in
      breastmilk during lactation may be a factor in the development of childhood
      overweight later in life. To investigate the association between trans fatty acid
      and adiposity, 96 mother-infant pairs (exclusive breastfed; mixed fed; and
      formula fed) at 3 months postpartum were interviewed; body composition was
      measured on site using the BOD POD and PEA POD for mothers and infants,
      respectively. SUBJECTS/METHODS: This was a cross-sectional study. Participants
      were recruited via convenience sampling from Athens-Clarke and surrounding
      counties of the state of Georgia. Data were analyzed using chi(2), analysis of
      variance and regression. RESULTS: There were no significant differences in
      maternal percent body fat by feeding group (32.70, 33.70, and 35.73%, for
      exclusive, mixed and formula feeding, respectively). Exclusively breastfed
      infants had higher percent body fat (24.87%) compared with their mixed-fed
      counterparts (22.15%) but not formula-fed infants (23.93). Mothers who consumed
      at least 4.5 g of trans fatty acids/day were 5.8 times more likely to have body
      fat >= 30% than those consuming less (odds ratio=5.81; 95% confidence interval
      (CI), 1.05, 32.32), and their infants were over two times more likely (odds
      ratio=2.13; 95% CI, 0.75, 6.01) to have body fat >= 24%. CONCLUSIONS: Trans fatty
      acid content of the maternal diet may be associated with both maternal and infant
      body composition in the early postpartum period. More research is warranted
      regarding maternal dietary and breastmilk fatty acid composition and their
      effects on maternal and infant body composition and the development of childhood
      overweight later in life.

PMID- 20823903
TI  - Presence of natural genetic resistance in Fraxinus excelsior (Oleraceae) to
      Chalara fraxinea (Ascomycota): an emerging infectious disease.
AB  - Fraxinus excelsior, common ash native to Europe, is threatened by a recently
      identified pathogenic fungus Chalara fraxinea, which causes extensive damage on
      ash trees across Europe. In Denmark, most stands are severely affected leaving
      many trees with dead crowns. However, single trees show notably fewer symptoms.
      In this study, the impact of the emerging infectious disease on native Danish ash
      trees is assessed by estimating presence of inherent resistance in natural
      populations. Disease symptoms were assessed from 2007 to 2009 at two different
      sites with grafted ramets of 39 selected clones representing native F. excelsior
      trees. A strong genetic variation in susceptibility to C. fraxinea infections was
      observed. No genetic or geographic structure can explain the differences, but
      strong genetic correlations to leaf senescence were observed. The results suggest
      that a small fraction of trees in the Danish population of ash possess
      substantial resistance against the damage. Though this fraction is probably too
      low to avoid population collapse in most natural or managed ash forests, the
      observed presence of putative resistance against the emerging infectious disease
      in natural stands is likely to be of evolutionary importance. This provides
      prospects of future maintenance of the species through natural or artificial
      selection in favour of remaining healthy individuals.

PMID- 20823902
TI  - Genetic structure and contrasting selection pattern at two major
      histocompatibility complex genes in wild house mouse populations.
AB  - The mammalian major histocompatibility complex (MHC) is a tightly linked cluster
      of immune genes, and is often thought of as inherited as a unit. This has led to
      the hope that studying a single MHC gene will reveal patterns of evolution
      representative of the MHC as a whole. In this study we analyse a 1000-km transect
      of MHC variation traversing the European house mouse hybrid zone to compare
      signals of selection and patterns of diversification at two closely linked MHC
      class II genes, H-2Aa and H-2Eb. We show that although they are 0.01 cM apart
      (that is, recombination is expected only once in 10 000 meioses), disparate
      evolutionary patterns were detected. H-2Aa shows higher allelic polymorphism,
      faster allelic turnover due to higher mutation rates, stronger positive selection
      at antigen-binding sites and higher population structuring than H-2Eb. H-2Eb
      alleles are maintained in the gene pool for longer, including over separation of
      the subspecies, some H-2Eb alleles are positively and others negatively selected
      and some of the alleles are not expressed. We conclude that studies on MHC genes
      in wild-living vertebrates can give substantially different results depending on
      the MHC gene examined and that the level of polymorphism in a related species is
      a poor criterion for gene choice.

PMID- 20823904
TI  - Thirty-four years of climatic selection in the land snail Theba pisana.
AB  - Few continuous, long-term studies have measured the intensity and variability of
      natural selection within a framework of clear adaptive hypotheses. In the snail
      Theba pisana, the proportion of effectively unbanded shells is higher in exposed
      habitats than in adjacent acacia thickets, which has been explained by
      microclimatic selection. Comparisons across an ecotone for 34 consecutive years
      determined the combined effects on morph frequencies of habitat and changes in
      weather conditions during summer. The long-term average (+/-s.e.) frequency of
      effectively unbanded shells was 0.577+/-0.011 in the open habitat when compared
      with 0.353+/-0.005 in the acacia. The persistent association of shell banding
      with habitat accounted for 34% of the variation in morph frequencies. Differences
      among years were also large, representing 23% of the variation. Higher
      proportions of effectively unbanded snails were associated with hotter, sunnier
      summers. Thus, temporal variation supports the hypothesis of microclimatic
      selection, consistent with the spatial association with habitat. Based on
      observed rates of change, the mean annual selection on this polymorphism was
      about 0.13, but with a large variance: s was as high as 0.5, but ?0.05 in about
      40% of the years. The large variance and frequent reversals in direction of
      selection indicate a potential for rapid genetic change, but with little net
      change in morph frequencies over three decades, highlighting the value of long
      term continuous studies of populations facing natural environmental variation.

PMID- 20823906
TI  - The singing genome.

PMID- 20823905
TI  - High genetic diversity at the extreme range edge: nucleotide variation at nuclear
      loci in Scots pine (Pinus sylvestris L.) in Scotland.
AB  - Nucleotide polymorphism at 12 nuclear loci was studied in Scots pine populations
      across an environmental gradient in Scotland, to evaluate the impacts of
      demographic history and selection on genetic diversity. At eight loci, diversity
      patterns were compared between Scottish and continental European populations. At
      these loci, a similar level of diversity (theta(sil)= ~0.01) was found in
      Scottish vs mainland European populations, contrary to expectations for recent
      colonization, however, less rapid decay of linkage disequilibrium was observed in
      the former (rho=0.0086+/-0.0009, rho=0.0245+/-0.0022, respectively). Scottish
      populations also showed a deficit of rare nucleotide variants (multi-locus
      Tajima's D=0.316 vs D=-0.379) and differed significantly from mainland
      populations in allelic frequency and/or haplotype structure at several loci.
      Within Scotland, western populations showed slightly reduced nucleotide diversity
      (pi(tot)=0.0068) compared with those from the south and east (0.0079 and 0.0083,
      respectively) and about three times higher recombination to diversity ratio
      (rho/theta=0.71 vs 0.15 and 0.18, respectively). By comparison with results from
      coalescent simulations, the observed allelic frequency spectrum in the western
      populations was compatible with a relatively recent bottleneck (0.00175 * 4N(e)
      generations) that reduced the population to about 2% of the present size.
      However, heterogeneity in the allelic frequency distribution among geographical
      regions in Scotland suggests that subsequent admixture of populations with
      different demographic histories may also have played a role.

PMID- 20823907
TI  - Kin assortment in juvenile shoals in wild guppy populations.
AB  - Grouping provides many potential benefits to individuals in terms of foraging and
      anti-predator protection. However, it has been suggested that individuals could
      gain additional benefits in terms of indirect fitness by grouping with kin.
      Surprisingly, the genetic composition of wild fish shoals and the importance of
      kin-associated shoaling remain poorly understood. The Trinidadian guppy (Poecilia
      reticulata) has life history traits that might promote kin structure of shoals
      such as internal fertilisation and small brood size in contrast to many other
      fish species. Even though previous studies did not find any indication of kin
      structure in shoals of adult guppies, it is possible that related juveniles
      remain together in shoals, partly because of lower mobility and because the
      advantages of kin association may change with age. Using 10 microsatellite
      markers, we conducted a genetic analysis on 40 shoals from four populations. Pair
      wise relatedness was inferred using a modified version of the software package
      COLONY and permutation tests were conducted to test the hypothesis that kin occur
      together in juvenile shoals more often than expected by chance. The frequency of
      sib dyads among juveniles within shoals was significantly larger than that
      between shoals in two high predation populations but not in two low predation
      populations. This finding contributes to the understanding of factors underlying
      shoal composition and highlights the potential of recent methodological advances
      for detecting such relationships.

PMID- 20823908
TI  - An experimental evaluation with Drosophila melanogaster of a novel dynamic system
      for the management of subdivided populations in conservation programs.
AB  - A dynamic method (DM) recently proposed for the management of captive subdivided
      populations was evaluated using the pilot species Drosophila melanogaster. By
      accounting for the particular genetic population structure, the DM determines the
      optimal mating pairs, their contributions to progeny and the migration pattern
      that minimize the overall co-ancestry in the population with a control of
      inbreeding levels. After a pre-management period such that one of the four
      subpopulations had higher inbreeding and differentiation than the others, three
      management methods were compared for 10 generations over three replicates: (1)
      isolated subpopulations (IS), (2) one-migrant-per-generation rule (OMPG), (3) DM
      aimed to produce the same or lower inbreeding coefficient than OMPG. The DM
      produced the lowest co-ancestry and equal or lower inbreeding than the OMPG
      method throughout the experiment. The initially lower fitness and lower variation
      for nine microsatellite loci of the highly inbred subpopulation were restored
      more quickly with the DM than with the OMPG method. We provide, therefore, an
      empirical illustration of the usefulness of the DM as a conservation protocol for
      captive subdivided populations when pedigree information is available (or can be
      deduced) and manipulation of breeding pairs is possible.

PMID- 20823909
TI  - Non-vesicular lipid transport by lipid-transfer proteins and beyond.
AB  - The movement of lipids within and between intracellular membranes is mediated by
      different lipid transport mechanisms and is crucial for maintaining the
      identities of different cellular organelles. Non-vesicular lipid transport has a
      crucial role in intracellular lipid trafficking and distribution, but its
      underlying mechanisms remain unclear. Lipid-transfer proteins (LTPs), which
      regulate diverse lipid-mediated cellular processes and accelerate vectorial
      transport of lipid monomers between membranes in vitro, could potentially mediate
      non-vesicular intracellular lipid trafficking. Understanding the mechanisms by
      which lipids are transported and distributed between cellular membranes, and
      elucidating the role of LTPs in intracellular lipid transport and homeostasis,
      are currently subjects of intensive study.

PMID- 20823911
TI  - Associations of Y-chromosome subdeletion gr/gr with the prevalence of Y
      chromosome haplogroups in infertile patients.
AB  - Microdeletions in azoospermia factor (AZF) region on distal Yq are associated
      with male infertility and spermatogenic failure due to intra-chromosomal
      homologous recombination between large nearly identical repeat amplicons and are
      found in ~10% of azoospermic and severe oligozoospermic cases. Although AZFc is
      deleted in azoospermia or oligozoospermia, no definitive conclusion has been
      drawn for the role of partial AZFc deletions to spermatogenic failure. Therefore,
      this study is planned to investigate the role of gr/gr subdeletions in
      individuals with spermatogenic failure and to find its relationship with Y
      chromosome haplogroups (HGs) in infertile men from Indian population. It is a
      case-control study involving 236 azoospermic, 182 oligospermic and 240 healthy
      normozoospermic men. We found 18 gr/gr, 11 b1/b3 and 2 b2/b3 subdeletions in
      azoospermic patients and 12 gr/gr, 5 b1/b3 and 4 b2/b3 subdeletions in
      oligospermic patients. However, we also found seven gr/gr deletions in
      normozoospermic men. Seven patients each with spermatogenic arrest and
      oligospermia who carry gr/gr subdeletions have deleted DAZ3/DAZ4 genes. A total
      of 11 patients with sertoli cell-only syndrome (SCOS) and 5 oligospermic patients
      with gr/gr subdeletions also have DAZ1/DAZ2 genes deleted indicating that
      deletions of DAZ genes contributed differently to damage to spermatogenic
      process. L1 HG is found in patients showing b1/b3 subdeletions, whereas HG H1a2
      and H1b were found in normozoospermic individuals with gr/gr subdeletions. Our
      results provide evidence of association between the occurrence of subdeletions
      and male infertility as well as the severity of the spermatogenic failure.

PMID- 20823912
TI  - In the heartland of Eurasia: the multilocus genetic landscape of Central Asian
      populations.
AB  - Located in the Eurasian heartland, Central Asia has played a major role in both
      the early spread of modern humans out of Africa and the more recent settlements
      of differentiated populations across Eurasia. A detailed knowledge of the
      peopling in this vast region would therefore greatly improve our understanding of
      range expansions, colonizations and recurrent migrations, including the impact of
      the historical expansion of eastern nomadic groups that occurred in Central Asia.
      However, despite its presumable importance, little is known about the level and
      the distribution of genetic variation in this region. We genotyped 26 Indo
      Iranian- and Turkic-speaking populations, belonging to six different ethnic
      groups, at 27 autosomal microsatellite loci. The analysis of genetic variation
      reveals that Central Asian diversity is mainly shaped by linguistic affiliation,
      with Turkic-speaking populations forming a cluster more closely related to East
      Asian populations and Indo-Iranian speakers forming a cluster closer to Western
      Eurasians. The scattered position of Uzbeks across Turkic- and Indo-Iranian
      speaking populations may reflect their origins from the union of different
      tribes. We propose that the complex genetic landscape of Central Asian
      populations results from the movements of eastern, Turkic-speaking groups during
      historical times, into a long-lasting group of settled populations, which may be
      represented nowadays by Tajiks and Turkmen. Contrary to what is generally
      thought, our results suggest that the recurrent expansions of eastern nomadic
      groups did not result in the complete replacement of local populations, but
      rather into partial admixture.

PMID- 20823913
TI  - Mutation rate estimates for 110 Y-chromosome STRs combining population and father
      son pair data.
AB  - Y-chromosome microsatellites (Y-STRs) are typically used for kinship analysis and
      forensic identification, as well as for inferences on population history and
      evolution. All applications would greatly benefit from reliable locus-specific
      mutation rates, to improve forensic probability calculations and interpretations
      of diversity data. However, estimates of mutation rate from father-son
      transmissions are available for few loci and have large confidence intervals,
      because of the small number of meiosis usually observed. By contrast, population
      data exist for many more Y-STRs, holding unused information about their mutation
      rates. To incorporate single locus diversity information into Y-STR mutation rate
      estimation, we performed a meta-analysis using pedigree data for 80 loci and
      individual haplotypes for 110 loci, from 29 and 93 published studies,
      respectively. By means of logistic regression we found that relative genetic
      diversity, motif size and repeat structure explain the variance of observed rates
      of mutations from meiosis. This model allowed us to predict locus-specific
      mutation rates (mean predicted mutation rate 2.12 * 10(-3), SD=1.58 * 10(-3)),
      including estimates for 30 loci lacking meiosis observations and 41 with a
      previous estimate of zero. These estimates are more accurate than meiosis-based
      estimates when a small number of meiosis is available. We argue that our
      methodological approach, by taking into account locus diversity, could be also
      adapted to estimate population or lineage-specific mutation rates. Such adjusted
      estimates would represent valuable information for selecting the most reliable
      markers for a wide range of applications.

PMID- 20823910
TI  - Molecular mechanisms of necroptosis: an ordered cellular explosion.
AB  - For a long time, apoptosis was considered the sole form of programmed cell death
      during development, homeostasis and disease, whereas necrosis was regarded as an
      unregulated and uncontrollable process. Evidence now reveals that necrosis can
      also occur in a regulated manner. The initiation of programmed necrosis,
      'necroptosis', by death receptors (such as tumour necrosis factor receptor 1)
      requires the kinase activity of receptor-interacting protein 1 (RIP1; also known
      as RIPK1) and RIP3 (also known as RIPK3), and its execution involves the active
      disintegration of mitochondrial, lysosomal and plasma membranes. Necroptosis
      participates in the pathogenesis of diseases, including ischaemic injury,
      neurodegeneration and viral infection, thereby representing an attractive target
      for the avoidance of unwarranted cell death.

PMID- 20823914
TI  - Genomic analysis of partial 21q monosomies with variable phenotypes.
AB  - Partial monosomy 21 was recently segregated into three regions associated with
      variable clinical severity. We describe 10 new patients, all examined by single
      nucleotide polymorphism (SNP) genotyping and G-banded karyotyping. Cohort A
      consisted of three patients seen in our medical genetics clinics with partial
      chromosome 21 monosomies. In two of these patients having terminal deletions
      (21q22.2-ter and 21q22.3-ter), the breakpoints differed by at least 812 Kb of
      sequence, containing seven RefSeq genes. A third patient had an interstitial
      hemizygous loss of 16.4 Mb (21q21.1-q22.11). All three patients had relatively
      mild phenotypes. Cohort B consisted of seven patients with partial chromosome 21
      monosomies who had a greater number of dysmorphic features and some major
      malformations; SNP genotypes were obtained from the Coriell Genetic Cell
      Repository. We also collected data on partial monsomy 21 cases from the DECIPHER
      database. This report of 10 new cases of 21q deletion and review of a total of 36
      confirms that deletion of the terminal region is associated with a mild
      phenotype, but suggests that deletion of regions 1 and 2 is compatible with life
      and have a variable phenotype perhaps relating more to other genetic and
      environmental variables than to genes in the interval.

PMID- 20823915
TI  - [Modification of nucleic acids using [3+2] dipolar cycloaddition of azides and
      alkynes].
AB  - The use of the reaction of azide and alkyne cycloaddition for the synthesis of
      nucleic acid conjugates and DNA oligomer analogues is considered. The data on
      chemical and enzymatic techniques of azides and alkynes introduction into DNA are
      summarized.

PMID- 20823916
TI  - [Molecular docking: role of intermolecular contacts in formation of complexes of
      proteins with nucleotides and peptides].
AB  - Knowledge of 3D-structure of protein-ligand complex is a major prerequisite for
      understanding the functioning mechanism of cellular proteins and membrane
      receptors. This is also of a great help in rational drug design projects. In the
      present paper we briefly review the molecular docking approaches used to predict
      possible orientation of a ligand in the protein binding site. The recent trends
      to improve the accuracy and efficiency of docking algorithms are demonstrated
      with the results obtained in Laboratory of Biomolecular Modeling. Particular
      attention is paid to protein-ligand hydrophobic and stacking interactions
      responsible for molecular recognition of ligand fragments. Such type of
      interactions are not always adequately represented in scoring criteria of docking
      applications that leads to mismatch in 3D-structure complexes predictions. That
      is why further inquiry of methods to account for these interactions is now the
      area of active research.

PMID- 20823917
TI  - [Synthesis and properties of the myelopeptides with differentiating activity].
AB  - The bone marrow myelopeptides Phe-Arg-Pro-Arg-Ile-Met-Thr-Pro (MP-4) and Val-Asp
      Pro-Pro (MP-6) have been synthesised by a classical method and by a solid phase
      synthesis. The differentiating activity of MP-4 and MP-6 in human leukemia cells
      HL-60 and K-562 has been studied. Both peptides induce terminal differentiation
      of these cell lines but the mechanism of action of peptides MP-4 and MP-6 is
      distinguished.

PMID- 20823918
TI  - [Peptide inhibitors of myosin light chain kinase. Development of peptidase
      resistant analogues].
AB  - Myosin light chain kinase (MLCK) is the key regulator of various forms of cell
      motility including endothelial and epithelial permeability in particular. One of
      the potential MLCK inhibitors to be used in humans is a membrane permeable
      peptide H-RKKYKYRRK-NH2 (L-PIK). In present work we used solid phase peptide
      synthesis and Fmoc-technology to produce five modifications of L-PIK. Based on
      (1)H NMR analysis revealed that these peptides demonstrated improved resistance
      to degradation in blood plasma. One of de novo synthesized peptides, L
      [MeArg(1)]PIK inhibited MLCK activity in vitro with the same efficiency as L-PIK
      whereas other modified peptides showed reduced inhibitory activity. D-amino acid
      analog of PIK was the least active inhibitor. Thus, we have demonstrated the
      possibility to produce an effective MLCK peptide inhibitor with increased
      resistance to biodegradation that is suitable for further pharmacological
      development.

PMID- 20823919
TI  - [Chimeric SHA-D domain ("SH3-Bergerac"): 3D-structure and dynamics studies in
      solution].
AB  - Protein SHA-D of "SH3-Bergerac" chimeric proteins family was constructed by
      substitution of beta-turn N47-D48 in spectrin SH3-domain by KATANDKTYE amino acid
      sequence. Structural and dynamics properties of SHA-D in solution were studied by
      with the help of high-resolution NMR. The extension of SHA-D polypeptide chain in
      comparison with wild type of protein WT-SH3 (~ 17%) practically doesn't affect
      almost the total molecule topology. 3D-structure of SHA-D is practically
      identical to the proteins of "SH3-Bergerac" family. However there are some
      differences in dynamic characteristics in the region of substitution. The G52D
      substitution in SHA-D protein results in a destabilization of the region
      insertion where the conditions for conformational exchange appear.
      Destabilization further affects the entire SHA- D molecule making its structure
      more labile.

PMID- 20823920
TI  - [Polymethylene derivatives of nucleic bases bearing omega-functional groups.
      VIII. omega-oxo-omega-phenylalkyl pyrimidines and purines].
AB  - Novel polymethylene derivatives of nucleic bases containing a phenylketo function
      in the omega-position of hydrocarbon chain were synthesized by alkylation of
      uracil, thymine, cytosine, hypoxantine, adenine, and N(2)-isobutyrylguanine with
      omega-chloro-1 -phenylalkan-1-ones, their physicochemical properties were
      studied.

PMID- 20823921
TI  - [Synthesis and biological properties of pyrimidine 4'-fluoro nucleosides and 4'
      fluoro uridine 5'-O-triphospate].
AB  - 4'- Fluoro-2',3'-O-isopropylidenecytidine was synthesized via interaction of 5'-O
      acetyl-4'-fluoro-2',3'-O-isopropylideneuridine with triazole and 4-chlorophenyl
      dichlorophosphate followed by ammonolysis. Treatment of 5'-O-acetyl-4'-fluoro
      2',3'-O-isopropylidenecytidine with hydroxylamine resulted in 5'-O-acetyl-4'
      fluoro-2',3'-O-isopropylidene-N(4)-hydroxycytidine. Subsequent removal of 2',3'-O
      isopropylidene groups gave 5'-O-acetyl derivatives of 4'-fluorouridine, 4'
      fluorocytidine and 4'-fluoro-N(4)-hydroxycytidine. 5'-O-Triphosphate of 4'
      fluorouridine was obtained in three steps starting from 4'-fluoro-2',3'-O
      isopropylideneuridine. The 4'-fluoro uridine 5'-O-triphospate was found to be an
      effective inhibitor of HCV RNA-dependent RNA polymerase, substrate for NTPase
      reaction, catalyzed by protein NS3 HCV (a rate of the analogue hydrolysis was
      similar to that of ATP) and an activator for helicase reaction (with an efficacy
      only three fold lower than that of ATP).

PMID- 20823922
TI  - [Condensed DNA particles formed in PCR with plasmid DNA: electron microscopy
      study].
AB  - An electron microscopy study of large-sized DNA microparticles produced in PCR
      with different gene-specific primers and plasmid DNAs is described. DNA
      microspheres of two distinct types were revealed in the all studied samples,
      namely smooth moderately electron-dense microspheres, and highly electron-dense
      particles with large thorns and offshoots. Singular microspheres have the average
      diameter of 1 mum, and their aggregates were up to 3 mum in dimensions. In
      addition, rare so-called three-dimensional net-like structures with various size
      (up to several micrometers) were observed. They consisted of different amounts of
      DNA nanoparticles, having the special compact topology. In some studied samples
      the discs (nanodiscs) of several dozens nm in thickness and up to 3 mum in
      diameter were revealed. It was shown that the quantity of net-like structures and
      nanodiscs sharply increases in asymmetric PCR. We also observed DNA nanowires of
      different length and thickness, nanodots, nanoparticles in the form of shits of
      paper as well as electron-dense spherical nanoparticles of big size. Aqueous
      suspensions of DNA microparticles were heated at 94 degrees C for 5 min and
      analyzed by electron microscopy. It was shown that microspheres in heated
      suspensions underwent partial melting; they lost a part of DNA, therefore details
      of their structure (ultrastructure) can be recognized. At the some time numerous
      tangles of nanowires appeared. Molecular mechanisms of the DNA micro- and
      nanoparticles formation are discussed.

PMID- 20823923
TI  - [New 4,4-difluoro-3alpha,4alpha-diaza-s-indacene (BODIPY) labeled sphingolipids
      for membrane studies].
AB  - The synthesis of a series of new fluorescence labeled sphingolipids containing
      4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3alpha,4alpha-diaza-s-indacene-8-yl (Me4
      BODIPY-8) group at omega-position of a fatty acyl residue is described. The
      obtained probes were used in studies of biological and model membrane systems.

PMID- 20823924
TI  - [Synthesis of new olean-18(19)-ene derivatives from allobetulin].
AB  - Effective synthesis of new olean-18(19)-ene triterpenoids based on interaction of
      allobetulin or its acetate with phosphorous oxychloride in pyridine under reflux
      is described. The structures of the synthesized 17-chloromethyl-oleane-18(19)
      enes have been established with the help of NMR-spectroscopy and X-Ray analysis.

PMID- 20823925
TI  - [Antiviral activity of 2,3-secotriterpenic hydrazones of lupane and 19beta,28
      epoxy-18alpha-oleanane type].
AB  - Novel hydrazones of lupane and 19beta,28-epoxy-18alpha-oleanane type have been
      synthesized via interaction of 2,3-secotriterpenic aldehydonitriles with
      substituted hydrazines. As a result of investigation of 2,3-secotriterpenic
      hydrazones antiviral activity to the strain "Indiana" of vesicular stomatitis
      virus on two models of mammal's line cell infection, acetylhydrazone 1-cyano-2,3
      seco-19beta,28-epoxy-18alpha-olean-3-al has been found to have a high
      prophylactic activity 0.00016 microg/ml to vesicular stomatitis virus and to
      inhibit a virus reproduction in primarily infected cells in 0.21 microg/ml
      concentration.

PMID- 20823926
TI  - [The dependence of cytotoxicity and antioxidant activity of ammonii derivatives
      of alkylphenols upon percularities of their structure].
AB  - Effect of seven structurally similar N, N-dimethyl-(4-hydroxyaryl)alkylammonium
      chlorides in the presence and in the absence of hydrogen peroxide on the survival
      of E. coli cells AB1157 and its isogenic strain BH910 defective in genes of
      repair enzymes has been analyzed. Among the studied compounds only chloride of
      N,N-dimethyl-(3,5-dimethyl-4-hydroxybenzyl)ammonium (C1) has no cytotoxic
      properties and increases the survive of the cells of both strains in the presence
      of H2O2 better than trolox (water soluble analog of alpha-tocopherol). C1
      analogs: 3-methyl-(5-di(tert-butyl)-4-hydroxybenzyl) and 3-(3,5-di(tert-butyl)-4
      hydroxyphenyl)propyl)amines derivatives effectively protected from H2O2 only
      mutant cells BH910. Among the structural analogs of C1 cytotoxicity increases at
      substitution of methyl groups in aromatic cycle by tert-butyl and cyclohexyl
      groups. Only C1 among the seven new compounds is the most promising antioxidant
      for the subsequent more detailed analysis.

PMID- 20823927
TI  - [Oligonucleotides with peptide internucleotide linkage. A novel class of modified
      oligonucleotides].
AB  - Oligonucleotide analogues with replacement of one or more internucleotide
      phosphodiester linkages with glycine, L- and D-alanine residues have been
      synthesized (C3'-NH-C(O)-CH(X)-NH-C(O)-C4', X = H, (S)-CH3 and (R)-CH3). The
      stability of the duplexes formed by the modified oligonucleotides and their wild
      type complements have been studied. Incorporation of glycine and L-alanine
      residues have been shown to substantially decrease the stability the modified
      duplexes in comparison with that of the wild-type ones (DeltaT(m) approximately 
      2 degrees C per modification), while the analogs with D-alanine-containing
      linkages appeared to form duplexes with increased stability (DeltaT(m),
      approximately +0.2 degrees C per modification).

PMID- 20823928
TI  - [New alkyl cationic glycerolipids with heterocyclic polar domain are responsible
      for disorders in the leukemia cells cycle and cells apoptosis].
AB  - A series of new modifications of alkyl cationic glycerolipids with hetero polar
      domain has been synthesized. The most active compound rac-N-(4-[(2-ethoxy-3
      octadecyloxy)prop-1-yloxycarbonyl]butyl)-N'-etylimidazoliyiodid in micromolar
      concentrations causes a delay of cell cycle in phase G1, DNA fragmentation and
      apoptosis of cell line leukemia.

PMID- 20823929
TI  - Ketamine versus propofol for strabismus surgery in children.
AB  - PURPOSE: To compare the effects of intravenous infusion of ketamine and propofol
      anesthesia in children undergoing strabismus surgery. METHODS: Sixty pediatric
      patients aged 4-11 years were enrolled for the study. Patients in Group K were
      infused ketamine 1-3 mg/kg/hr (n = 30) and patients in Group P were infused with
      propofol 6-9 mg/kg/hr (n = 30). After giving fentanyl 1 mug/kg and rocuronium
      bromide 0.5 mg/kg, patients were intubated. RESULTS: The consumption of
      anesthetics (P = 0.0001) and antiemetics (P = 0.004), the incidence of
      oculocardiac reflex (P = 0.02) in Group K were significantly lower than in Group
      P. The recovery time (P = 0.008), postoperative agitation score (P = 0.005), Face
      Pain Scale (P = 0.001), Ramsay Sedation Score (P = 0.01) during awakening and at
      postoperative 30th min (P = 0.02) in Group K were significantly lower than in
      Group P. The postoperative agitation score during awakening was significantly
      lower than the preoperative values in Group K (P = 0.0001). CONCLUSIONS: The
      infusion of ketamine is more advantageous than the infusion of propofol in
      children for use in strabismus surgery.

PMID- 20823930
TI  - Endoscopy-guided vitreoretinal surgery following penetrating corneal injury: a
      case report.
AB  - INTRODUCTION: Severe ocular trauma requires emergency surgery, and a fresh
      corneal graft may not always be available. We describe a case of perforating eye
      injury with corneal opacity, suspected endophthalmitis, and an intraocular
      foreign body. The patient was successfully treated with a two-step procedure
      comprising endoscopy-guided vitrectomy followed by corneal transplantation. This
      surgical technique offers a good option to vitrectomy with simultaneous
      keratoplasty in emergency cases where no graft is immediately available and there
      is the possibility of infection due to the presence of a foreign body. CASE
      PRESENTATION: A 55-year-old Japanese woman was referred to our hospital with a
      perforating corneal and lens injury sustained with a muddy ferrous rod. Primary
      corneal sutures and lensectomy were performed immediately. Vitreoretinal surgery
      was required due to suspected endophthalmitis, vitreous hemorrhage, retinal
      detachment, dialysis and necrosis of the peripheral retina. Instead of
      conventional vitrectomy, endoscopy-guided vitreous surgery was performed with the
      Solid Fiber Catheter AS-611 (FiberTech, Tokyo, Japan) due to the presence of
      corneal opacity and the unavailability of a donor cornea. The retina was
      successfully attached with the aid of a silicon oil tamponade. Following removal
      of the silicon oil at 3 months after surgery, penetrating keratoplasty and
      intraocular lens implantation with ciliary sulcus suture fixation were performed.
      At 6 months after penetrating keratoplasty, the graft remained clear and visual
      acuity was 20/40. CONCLUSION: Primary endoscopic surgery for vitreoretinal
      complications in eyes with perforating injury performed prior to penetrating
      keratoplasty appears to be advantageous in terms of avoiding damage to the
      corneal endothelium.

PMID- 20823932
TI  - Visual outcome of ranibizumab therapy for neovascular age related macular
      degeneration in the black population: a report of five cases.
AB  - INTRODUCTION: Neovascular age related macular degeneration (AMD) is relatively
      uncommon in the black population. We report the 12-month outcome of ranibizumab
      therapy in five black patients with choroidal neovascular membrane (CNV)
      secondary to AMD. MATERIAL AND METHODS: Retrospective analysis of a prospective
      audit database maintained for all patients on ranibizumab therapy in a retinal
      specialist unit that caters to a multi-ethnic cohort in London, United Kingdom.
      RESULTS: At 12 months, all the 5 patients maintained stable vision (loss of less
      than 15 ETDRS letters). However, none of them gained more than 15 ETDRS letters.
      All eyes showed early subretinal fibrosis while 2 patients showed extended areas
      of retinal pigment atrophy. CONCLUSION: Our case studies indicate that
      ranibizumab stabilizes the vision in black patients with CNV secondary to AMD but
      they tend to develop early subretinal fibrosis and retinal pigment atrophy.

PMID- 20823931
TI  - Topical ganciclovir in the treatment of acute herpetic keratitis.
AB  - Herpetic keratitis is caused by herpes simplex virus (HSV) and is a common cause
      of corneal blindness. Following a primary ocular herpetic infection, latency of
      the virus occurs, followed by subsequent recurrences of herpetic keratitis. Such
      recurrences may lead to structural damage of the cornea. Recurrent herpetic
      keratitis is a common indication for corneal transplantation. Recurrences of
      herpetic keratitis in the corneal graft may lead to corneal graft rejection.
      Several antiviral agents for HSV are available, including the thymidine analogs.
      Prolonged use of thymidine analogs may lead to toxicity of the ocular surface,
      including epithelial keratitis, corneal ulcers, follicular conjunctivitis, and
      punctal occlusions. Availability of topical antiviral agents that are safe and
      effective in the treatment and prophylaxis of herpetic keratitis is highly
      desirable. Ganciclovir is a potent inhibitor of members of the herpes virus
      family. The drug has been used systemically for the treatment of cytomegalovirus
      (CMV) retinitis. Its hematologic toxicity secondary to systemic administration
      led to its limited use in herpetic infections. On the other hand, topical
      ganciclovir has been shown to be as safe and effective as acyclovir in the
      treatment of herpetic epithelial keratitis. Furthermore, topical ganciclovir can
      reach therapeutic levels in the cornea and aqueous humor following topical
      application. Several clinical trials have shown that topical ganciclovir 0.15%
      ophthalmic gel is safe and effective in the treatment and prophylaxis of herpetic
      epithelial disease. Long-term use of ganciclovir ophthalmic gel in patients with
      penetrating keratoplasty following herpetic keratitis has prevented recurrences
      of the disease. Topical ganciclovir ophthalmic gel is well tolerated, does not
      cause toxic effects on the ocular surface, and does not cause hematologic
      abnormalities. Clinical studies have underscored the potential role of
      ganciclovir ophthalmic gel in the treatment and prophylaxis of herpetic
      epithelial keratitis. Future randomized, controlled, multicenter, prospective
      clinical trials are needed to assess the long-term safety and efficacy of topical
      ganciclovir in the treatment and prevention of herpetic keratitis and uveitis.

PMID- 20823933
TI  - Case of endogenous endophthalmitis caused by Streptococcus equisimilis.
AB  - We report a rare case of endogenous endophthalmitis caused by Streptococcus
      equisimilis. A 74-year-old woman with endocarditis developed endogenous
      endophthalmitis. The patient underwent emergency mitral valvuloplasty, and
      intravitreal and subconjunctival injections of vancomycin and meropenem. After
      the surgery, she was treated with topical antibiotics, ointment, intravenous
      gentamicin and intravenous penicillin G potassium. The causative organism was
      identified as S. equisimilis. S. equisimilis should be considered as a pathogen
      that can cause severe endogenous endophthalmitis.

PMID- 20823934
TI  - Cytotoxicity of prostaglandin analog eye drops preserved with benzalkonium
      chloride in multiple corneoconjunctival cell lines.
AB  - PURPOSE: This study evaluated the cytotoxicity of five prostaglandin analog
      ophthalmic solutions on four ocular surface cell lines, ie, Chang (human
      conjunctiva), SIRC (rabbit cornea), RC-1 (rabbit cornea), and BCE C/D-1b (bovine
      cornea). METHODS: Cell viability was measured by neutral red and MTT assays in
      cells treated for 10, 30, or 60 minutes with various doses of prostaglandins
      (undiluted, and 2- and 10-fold dilutions). The number of cell lines with
      viability >/=50% in the presence of selected dilution of the drug (CVS(50)) was
      used for comparison. In addition, 24 cell viability comparisons (four cell lines,
      two assays, and three exposure times) were made between latanoprost
      (Xalatan((R))) and each other solution at each dose. A comparison between the
      newly introduced tafluprost (Tapros((R))) with 0.01% benzalkonium chloride was
      also made. RESULTS: The order of cell viability determined by CVS(50) was
      Travatan Z((R)) (travoprost with the SofZia system) > Tapros >/= Travatan((R))
      (travoprost) = Xalatan > Rescula((R)) (unoproston). This was consistent with the
      results of direct comparisons between Xalatan and the other drugs. There was no
      clear difference in cell viability between Tapros and benzalkonium chloride.
      CONCLUSIONS: Use of two assays, multiple cell lines, and various dilutions and
      exposure times provided a unique evaluation of cytotoxicity among ophthalmic
      solutions. CVS(50) was useful for comparison of the cell viability of the
      solutions.

PMID- 20823935
TI  - Evaluation of ocular surface glycocalyx using lectin-conjugated fluorescein.
AB  - PURPOSE: A glycocalyx plays important roles in the ocular surface epithelium, but
      there is no direct simple method to evaluate ocular surface glycocalyx. We tested
      a wheat germ agglutinin conjugate of fluorescein (F-WGA) as a marker to
      demonstrate ocular surface glycocalyx in vivo. METHODS: After a 5% F-WGA solution
      was applied to the eyes of eight healthy volunteers, fluorescent intensities of
      the central cornea and bulbar conjunctiva were measured by fluorophotometry. A
      10% fluorescein-conjugated dextran solution served as the control. Changes in
      fluorescent intensities of the ocular surface following a challenge with 5% N
      acetyl cysteine, a conventional mucolytic agent, were tested in the second
      experiment. Saline instillation served as a control. RESULTS: The ocular surface
      was diffusely stained by F-WGA. Breakup of the precorneal tear film was not
      apparent, possibly because F-WGA was bound to the glycocalyx of the ocular
      surface epithelium. F-WGA fluorescent intensities were high in the superior,
      nasal, and inferior regions of the bulbar conjunctiva and low in the temporal
      conjunctiva and cornea. No such regional differences were observed with
      fluorescein-conjugated dextran. F-WGA fluorescent intensities decreased
      significantly with N-acetyl cysteine instillation, whereas they were not affected
      by saline instillation. CONCLUSION: The fluorophotometric method may be used to
      evaluate the glycocalyx quantitatively in the ocular surface in vivo.

PMID- 20823936
TI  - Improved centration of the type 1 Boston Keratoprosthesis in donor carrier
      tissue.
AB  - The type 1 Boston Keratoprosthesis preparation requires a 3-mm central punch and
      an 8.5 mm or larger punch in the carrier tissue. These punches are ideally
      concentric, but we have found difficulty in achieving concentric punches when the
      larger punch is performed first. We present a modification in the preparation
      procedure to help minimize centration error.

PMID- 20823937
TI  - Erratum.
AB  - [This corrects the article on p. 587 in vol. 3, PMID: 19898663.].

PMID- 20823938
TI  - Cortical reactivity and effective connectivity during REM sleep in humans.
AB  - We recorded the electroencephalographic (EEG) responses evoked by transcranial
      magnetic stimulation (TMS) during the first rapid eye movement (REM) sleep
      episode of the night and we compared them with the responses obtained during
      previous wakefulness and NREM sleep. Confirming previous findings, upon falling
      into NREM sleep, cortical activations became more local and stereotypical,
      indicating a significant impairment of the intracortical dialogue. During REM
      sleep, a state in which subjects regain consciousness but are almost paralyzed,
      TMS triggered more widespread and differentiated patterns of cortical activation,
      that were similar to the ones observed in wakefulness. Similarly, TMS/hd-EEG may
      be used to probe the internal dialogue of the thalamocortical system in brain
      injured patients that are unable to move and communicate.

PMID- 20823939
TI  - An experimental test of noise-dependent voice amplitude regulation in Cope's grey
      treefrog (Hyla chrysoscelis).
AB  - One strategy for coping with the constraints on acoustic signal reception posed
      by ambient noise is to signal louder as noise levels increase. Termed the
      'Lombard effect', this reflexive behaviour is widespread among birds and mammals
      and occurs with a diversity of signal types, leading to the hypothesis that voice
      amplitude regulation represents a general vertebrate mechanism for coping with
      environmental noise. Support for this evolutionary hypothesis, however, remains
      limited due to a lack of studies in taxa other than birds and mammals. Here, we
      report the results of an experimental test of the hypothesis that male grey
      treefrogs increase the amplitude of their advertisement calls in response to
      increasing levels of chorus-shaped noise. We recorded spontaneously produced
      calls in quiet and in the presence of noise broadcast at sound pressure levels
      ranging between 40 dB and 70 dB. While increasing noise levels induced
      predictable changes in call duration and rate, males did not regulate call
      amplitude. These results do not support the hypothesis that voice amplitude
      regulation is a generic vertebrate mechanism for coping with noise. We discuss
      the possibility that intense sexual selection and high levels of competition for
      mates in choruses place some frogs under strong selection to call consistently as
      loudly as possible.

PMID- 20823941
TI  - Perception of visually masked stimuli by individuals with aphasia: A
      methodological assessment and preliminary theoretical implications.
AB  - BACKGROUND: Studies of the automatic processes supporting language processing and
      dysfunction in aphasia often rely on priming paradigms. The ability to
      confidently interpret these studies in terms of understanding the relative
      contributions of automatic vs. controlled processing, however, depends on the
      ability to isolate only automatic processes. One way this may be accomplished is
      through the use of visual masking. The effective use of visual masking, however,
      depends on verification that there was no task-relevant information consciously
      available from the prime item. AIMS: The study reported here was designed to
      assess the visibility of visually masked stimuli, for both typical adults and
      adults with aphasia. METHODS #ENTITYSTARTX00026; PROCEDURES: This experiment
      involved 31 typical adults and 21 individuals with aphasia. Visual masking
      sequences were presented on a computer screen, with 11 different interstimulus
      intervals assessed. Participants made lexical decisions on the masked stimuli.
      The two participant groups were compared in terms of their ability to distinguish
      the word/non-word status of masked stimuli at the various intervals. OUTCOMES
      #ENTITYSTARTX00026; RESULTS: Participants with aphasia showed an overall poorer
      ability to discriminate between visually masked words and non-words than typical
      adults. CONCLUSIONS: The visual masking sequence effectively interfered with task
      relevant conscious perception of some masked stimuli for typical adults and all
      masked stimuli for participants with aphasia. This finding, combined with
      preliminary data collected on a similar task that involved a simple
      presence/absence judgment on masked items, suggests that there may be differences
      in the ability of individuals with aphasia to process rapidly presented masked
      stimuli, even when there is minimal linguistic processing required.

PMID- 20823940
TI  - Genetic and Environmental Influences on Inattention, Hyperactivity-Impulsivity,
      and Reading: Kindergarten to Grade 2.
AB  - Twin children from Australia, Scandinavia and the USA were assessed for
      inattention, hyperactivity-impulsivity and reading across the first three school
      years. Univariate behavior-genetic analyses indicated substantial heritability
      for all three variables in all years. Longitudinal analyses showed one genetic
      source operating across the time span and a second entering in the second school
      year for each variable, though possibly not reliable for inattention. Other
      analyses confirmed previous findings of pleiotropy (shared genes) between
      inattention and reading, and showed that this genetic overlap is in place from
      kindergarten onwards and is restricted to one of the genetic sources that affect
      reading and inattention. The results extend previous conclusions about the
      developmental trajectories of inattention, hyperactivity-impulsivity, and reading
      and their relationships. Limitations of this studyare discussed, as are
      educational implications.

PMID- 20823942
TI  - Spiral column configuration for protein separation by high-speed countercurrent
      chromatography.
AB  - Retention of the stationary phase of aqueous-aqueous polymer phase systems is
      improved by a spiral column configuration which utilizes the radially acting
      centrifugal force along the spiral pitch to retain the heavier phase in the outer
      portion and the lighter phase in the inner portion of the spiral channel. For the
      separation of proteins which has low mass transfer rates, the system needs
      further modification of the separation channel to interrupt the laminar flow and
      enhance mixing of the two phases. Two spiral column assemblies were developed,
      one using a disk with spiral grooves and the other, the spiral tube support which
      accommodates the multiple spiral layers made from a single piece of fluorinated
      plastic tubing. In the spiral disk assembly, the best protein separation is
      achieved by the mixer-settler system which vigorously mixes two phases by
      vibrating glass beads placed in every other section of barricaded spiral channel,
      while in the spiral tube assembly the partition efficiency of proteins is
      enhanced by compressing the tubing to interrupt the laminar flow of the mobile
      phase. In both systems protein samples were well resolved by choosing the
      suitable elution modes.

PMID- 20823943
TI  - Children's Perceptions of Maternal Hostility as a Mediator of the Link between
      Discipline and Children's Adjustment in Four Countries.
AB  - Using data from 195 dyads of mothers and children (age range = 8-12 years; M =
      10.63) in four countries (China, India, the Philippines, and Thailand), this
      study examined children's perceptions of maternal hostility as a mediator of the
      links between physical discipline and harsh verbal discipline and children's
      adjustment. Both physical discipline and harsh verbal discipline had direct
      effects on mothers' reports of children's anxiety and aggression; three of these
      four links were mediated by children's perceptions of maternal hostility. In
      contrast, there were no significant direct effects of physical discipline and
      harsh verbal discipline on children's reports of their own anxiety and
      aggression. Instead, both physical discipline and harsh verbal discipline had
      indirect effects on the outcomes through children's perceptions of maternal
      hostility. We identified a significant interaction between perceived
      normativeness and use of harsh verbal discipline on children's perception of
      maternal hostility, but children's perception of the normativeness of physical
      discipline did not moderate the relation between physical discipline and
      perceived maternal hostility. The effects of harsh verbal discipline were more
      adverse when children perceived that form of discipline as being nonnormative
      than when children perceived that form of discipline as being normative. Results
      are largely consistent with a theoretical model positing that the meaning
      children attach to parents' discipline strategies is important in understanding
      associations between discipline and children's adjustment, and that cultural
      context is associated with children's interpretations of their parents' behavior.

PMID- 20823944
TI  - On-site Basic Health Screening and Brief Health Counseling of Chronic Medical
      Conditions for Veterans in Methadone Maintenance Treatment.
AB  - BACKGROUND: In order to improve the delivery of health services for chronic
      medical conditions in our methadone clinic, we added an onsite health screening
      and brief health counseling to the treatment plans for patients receiving
      methadone maintenance treatment at the Atlanta Veterans Affairs Medical Center
      (VAMC). We then conducted a follow up retrospective chart review to assess
      whether this intervention improved health outcome for those patients. METHODS: We
      reviewed the charts of one hundred and two patients who received treatment at
      Atlanta VAMC methadone clinic between 2002 and 2008. We sought to determine
      whether our increased health education and screening intervention was associated
      with improved: 1) Improved drug addiction outcome (as measured by comparing
      percentage of opiate and cocaine positive drug screens from admission to most
      recent). 2) Basic health screening, (as measured by the patient's compliance with
      primary care physicians (PCP) appointments and current smoking status). 3)
      Management of co-occurring medical conditions (as measured by levels of LDL
      cholesterol, hemoglobin A1c, and systolic blood pressure (SBP). 4) Presence of
      QTc prolongation (difference in QTc between baseline and most recent EKG).
      RESULTS: Illicit drug use (opiate and cocaine) markedly decreased in patients
      overall. The effect was more robust for those successfully "retained" (n=55,
      p<0.0001) in treatment, compared to those who "dropped out" (n=40, p=0.05) of
      treatment. Compliance with PCP appointments was high (82% and 88% before and
      after the onsite intervention, respectively) for "retained" patients. LDL
      cholesterol level was within normal range for all patients. A1c improved by 40%
      after the onsite intervention as reflected by the decreased percentage of
      patients with A1c > 7 % from before to after the intervention (90% vs. 50%,
      p=0.05). However, the prevalence of uncontrolled hypertension did not
      significantly improve after the onsite intervention (38% vs. 28%, p=0.34). As
      might be expected with MMT, the prevalence of QTc prolongation actually increased
      from 399 m sec. (+/- 92) to 439 msec. (+/- 22) after the onsite intervention
      (p=0.003). CONCLUSIONS: Our retrospective study supports the previous literature
      that methadone maintenance therapy is effective in reducing illicit drug use.
      Although patients with history of heroin dependence and in methadone maintenance
      treatment are at increased risk for chronic medical conditions like hepatitis C
      and diabetes, there are minimal federal guidelines for medical care, except than
      a physical exam upon admission, and basic screening for some infectious diseases
      e.g. HIV and Hepatitis C for those patients. Our study demonstrated the need for
      and potential benefit of enhancing the delivery of health promotion services for
      chronic medical conditions in methadone maintained patients. Improving management
      of hepatitis C, diabetes, hypertension, and other related conditions, in this
      high risk, difficult-to-treat, and underserved population may reduce their
      morbidity and premature mortality.

PMID- 20823945
TI  - Alcohol prevalence and attitudes among adults and adolescents: Their relation to
      early adolescent alcohol use in rural communities.
AB  - Although research has identified numerous neighborhood mechanisms influencing
      urban adolescent risk behaviors, less is known about how community contexts
      influence rural adolescents. This study explores perceived controls against
      adolescent drinking (i.e., tolerance of community adolescent alcohol use),
      adolescent perceptions of community supportiveness, and the prevalence of
      community alcohol use exhibited by adolescents and adults. Multilevel analyses
      were applied to 1,424 6(th) through 8(th) grade students residing in 22 rural
      communities in the Northern Plains. Perceptions of tolerance, prevalence, and
      support from 790 parents, teachers, and community leaders were also collected.
      Analyses revealed that community supportiveness and controls against drinking
      reduced both the decision to try alcohol and past month use among early
      adolescents. Adolescents were more likely to have ever tried alcohol if they
      lived in a community with higher peer prevalence than higher levels of adult
      alcohol prevalence, but in communities where peer drinking was lower; adolescents
      were more likely to have tried alcohol if they lived in a high adult-prevalence
      community. Perceived peer drinking was not related to past month use.

PMID- 20823947
TI  - The Healthy Young Men's Study: Sampling Methods to Recruit a Random Cohort of
      Young Men Who Have Sex with Men.
AB  - Recruiting a scientifically sound cohort of young men who have sex with men
      (YMSM) is an enduring research challenge. The few cohort studies that have been
      conducted to date on YMSM have relied on non-probability sampling methods to
      construct their cohorts. While these studies have provided valuable information
      about HIV risk behaviors among YMSM, their generalizability to broader YMSM
      populations is limited.In this paper the authors describe a venue-based sampling
      methodology used to recruit a large and diverse cohort of YMSM from public venues
      in Los Angeles County. Venue-based sampling is a multi-stage, probability
      sampling design that uses standard outreach techniques and standard survey
      methods to systematically enumerate, sample, and survey hard-to-reach
      populations. The study design allowed the authors to estimate individual,
      familial and interpersonal psychosocial factors associated with HIV risk and
      health seeking behaviors for a cohort of YMSM with known properties. Study
      participants completed an extensive baseline survey and over a two year period
      will complete four follow-up surveys at six-month intervals. The baseline survey
      was administered in both English and Spanish.

PMID- 20823946
TI  - Review of Interventions to Improve Family Engagement and Retention in Parent and
      Child Mental Health Programs.
AB  - Engaging and retaining families in mental health prevention and intervention
      programs is critically important to insure maximum public health impact. We
      evaluated randomized-controlled trials testing methods to improve family
      engagement and retention in child mental health programs published since 1980 (N
      = 17). Brief, intensive engagement interventions in which providers explicitly
      addressed families' practical (e.g. schedules, transportation) and psychological
      (e.g. family members' resistance, beliefs about the treatment process) barriers
      as they entered treatment were effective in improving engagement in early
      sessions. The few interventions found to produce long-term impact on engagement
      and retention integrated motivational interviewing, family systems, and enhanced
      family stress and coping support strategies at multiple points throughout
      treatment. Few interventions have been tested in the context of prevention
      programs. There are promising approaches to increasing engagement and retention;
      they should be replicated and used as a foundation for future research in this
      area.

PMID- 20823948
TI  - Does fertility trump monogamy?
AB  - Monogamous animals face an interesting dilemma: if and when to terminate a
      nonproductive relationship. To address this issue, we asked whether reproductive
      compatibility is a criterion for maintaining a monogamous pair-bond between
      mates. Prairie voles (Microtus ochrogaster), are small rodents that form long
      term, monogamous pair-bonds evidenced by a strong preference for their familiar
      partners, and thus are an excellent model animal in which to study mate-fidelity.
      Accordingly, we examined partner-preferences by male prairie voles and related
      their behavior to the reproductive status of their mates. We found that, when
      given a choice between their familiar female partner and a stranger, male prairie
      voles differ in their responses depending on the pregnancy status of the partner.
      Males that were paired with females for two weeks displayed mate-fidelity only
      when mating had been initiated within ~48 hours after pairing. In contrast, males
      whose mates experienced a delay in the onset of sexual receptivity displayed non
      selective affiliative behavior. We also found that, in addition to being
      appropriately timed, mating must be successful. Males that mated with
      ovariectomized females for whom pregnancy was precluded did not display mate
      fidelity even though mating was initiated within the proper timeframe. These
      observations of mate-fidelity only when the partner's pregnancy was sufficiently
      advanced relative to the duration of the pairing suggest that mating must be both
      successful and timely. Thus, reproductive compatibility can influence mate
      fidelity.

PMID- 20823950
TI  - The Role of Primary Cilia in Mesenchymal Stem Cell Differentiation: A Pivotal
      Switch in Guiding Lineage Commitment.
AB  - Primary cilia are sensory organelles that have been shown to play a critical role
      in lineage commitment. It was our hypothesis that the primary cilium is necessary
      for chemically induced differentiation of human mesenchymal stem cells (MSC). To
      investigate this, polaris siRNA was used to inhibit the primary cilia and the
      mRNA levels of transcription factors Runx2, PPARgamma were measured by RT PCR as
      markers of osteogenic, adipogenic and chondrogenic differentiation, respectively.
      MSCs with inhibited primary cilia had significantly decreased basal mRNA
      expression levels of all three lineages specific transcription factors indicating
      that primary cilia are critical in multiple differentiation pathways.
      Furthermore, to determine if primary cilia play a role in the differentiation
      potential of MSCs, progenitor cells transfected with either scrambled or polaris
      siRNA were cultured in osteo-inductive, chondro-inductive, or adipo-inductive
      media and lineage commitment was ascertained. Interestingly, within 24 h of
      culture, cells transfected with polaris siRNA in both osteogenic and adipogenic
      media lost adhesion and released from the slides; however MSCs in chondrogenic
      media as well as cells transfected with scrambled siRNA did not. These results
      suggest that the primary cilium is necessary for the normal progression of
      chemically induced osteogenic and adipogenic differentiation. As a control, the
      experiment was repeated with NIH3T3 fibroblasts and none of the effects of
      inhibited primary cilia were observed indicating that the loss of adhesion may be
      specific to MSCs. Furthermore after biochemically inducing the cells to
      differentiate, polaris knockdown resulted in abrogation of both Runx2 and
      PPARgamma mRNA while SOX9 mRNA expression was significantly lower. These results
      suggest that primary cilia play an essential role not only in the initiation of
      both osteogenic and adipogenic differentiation, but also in maintaining the
      phenotype of differentiated cells. Interestingly, chondrogenic differentiation
      appeared less dependent on a functional primary cilium.

PMID- 20823949
TI  - Language of the aging brain: Event-related potential studies of comprehension in
      older adults.
AB  - Normal aging brings increased richness in knowledge and experience as well as
      declines in cognitive abilities. Event-related brain potential (ERP) studies of
      language comprehension corroborate findings showing that the structure and
      organization of semantic knowledge remains relatively stable with age.
      Highlighting the advantages of the temporal and functional specificity of ERPs,
      this survey focuses on age-related changes in higher-level processes required for
      the successful comprehension of meaning representations built from multiple
      words. Older adults rely on different neural pathways and cognitive processes
      during normal, everyday comprehension, including a shift away from the predictive
      use of sentential context, differential recruitment of neural resources, and
      reduced engagement of controlled processing. Within age groups, however, there
      are important individual differences that, for example, differentiate a subset of
      older adults whose processing patterns more closely resemble that of young
      adults, providing a window into cognitive skills and abilities that may mediate
      or moderate age-related declines.

PMID- 20823952
TI  - Diverse routes to oscillation death in a coupled oscillator system.
AB  - We study oscillation death (OD) in a well-known coupled-oscillator system that
      has been used to model cardiovascular phenomena. We derive exact analytic
      conditions that allow the prediction of OD through the two known bifurcation
      routes, in the same model, and for different numbers of coupled oscillators. Our
      exact analytic results enable us to generalize OD as a multiparameter-sensitive
      phenomenon. It can be induced, not only by changes in couplings, but also by
      changes in the oscillator frequencies or amplitudes. We observe synchronization
      transitions as a function of coupling and confirm the robustness of the phenomena
      in the presence of noise. Numerical and analogue simulations are in good
      agreement with the theory.

PMID- 20823951
TI  - Developmental Precursors of Number of Sexual Partners from Age 16 to 22.
AB  - This study examines family and child characteristics, parent and peer
      relationships, and early adolescent behavior as statistical predictors of
      trajectories of number of sexual partners from mid-adolescence through early
      adulthood using data from 527 participants in the Child Development Project.
      Early adolescent developmental antecedents accounted for modest variance in
      number of sexual partners. Latent growth models revealed that African American
      race, more advanced pubertal development, lower parental monitoring knowledge,
      association with more deviant peers, and lower GPA in early adolescence each
      predicted having more sexual partners at age 16. In addition, non-African
      American race, lower child IQ, higher parental monitoring knowledge, and lower
      early adolescent internalizing problems each was associated with a higher rate of
      growth in number of sexual partners over time at the ages following 16. Latent
      growth mixture modeling identified subgroups with distinct trajectories of
      involvement with sexual partners that were associated with family and child
      characteristics, parent and peer relationships, and behavior in early
      adolescence.

PMID- 20823954
TI  - "Like a Devoted Army": Medicine, Heroic Masculinity, and the Military Paradigm in
      Victorian Britain.

PMID- 20823953
TI  - Implications of Research on Computer Delivered Normative Feedback for Social
      Norms Campaigns.

PMID- 20823955
TI  - Physics of brain dynamics: Fokker-Planck analysis reveals changes in EEG delta
      and theta activity during anaesthesia.
AB  - We use drift and diffusion coefficients to reveal interactions between different
      oscillatory processes underlying a complex signal and apply the method to EEG
      delta and theta frequencies in the brain. By analysis of data recorded from rats
      during anaesthesia we consider the stability and basins of attraction of fixed
      points in the phase portrait of the deterministic part of the retrieved
      stochastic process. We show that different classes of dynamics are associated
      with deep and light anaesthesia, and we demonstrate that the predominant
      directionality of the interaction is such that theta drives delta.

PMID- 20823956
TI  - Chart smart: a need for documentation and billing education among emergency
      medicine residents?
AB  - OBJECTIVE: The healthcare chart is becoming ever more complex, serving
      clinicians, patients, third party payers, regulators, and even medicolegal
      parties. The purpose of this study was to identify our emergency medicine (EM)
      resident and attending physicians' current knowledge and attitudes about billing
      and documentation practices. We hypothesized that resident and attending
      physicians would identify billing and documentation as an area in which residents
      need further education. METHODS: We gave a 15-question Likert survey to resident
      and attending physicians regarding charting practices, knowledge of billing and
      documentation, and opinions regarding need for further education. RESULTS: We
      achieved a 100% response rate, with 47% (16/34) of resident physicians
      disagreeing or strongly disagreeing that they have adequate training in billing
      and documentation, while 91% (31/34) of residents and 95% (21/22) of attending
      physicians identified this skill as important to a resident's future practice.
      Eighty-two percent (28/34) of resident physicians and 100% of attending
      physicians recommended further education for residents CONCLUSION: Residents in
      this academic EM department identified a need for further education in billing
      and documentation practices.

PMID- 20823957
TI  - The chief resident role in emergency medicine residency programs.
AB  - STUDY OBJECTIVES: Although other specialties have examined the role of the chief
      resident (CR), the role and training of the emergency medicine (EM) CR has
      largely been undefined. METHODS: A survey was mailed to all EM CRs and their
      respective program directors (PD) in 124 EM residency programs. The survey
      consisted of questions defining demographics, duties of the typical CR, and
      opinions regarding the level of support and training received. Multiple choice,
      Likert scale (1 strong agreement, 5 strong disagreement) and short-answer
      responses were used. We analyzed associations between CR and PD responses using
      Chi-square, Student's T and Mann-Whitney U tests. RESULTS: Seventy-six percent of
      CRs and 65% of PDs responded and were similar except for age (31 vs. 42 years;
      p<0.001). CR respondents were most often male, in year 3 of training and held the
      position for 12 months. CRs and PDs agreed that the assigned level of
      responsibility is appropriate (2.63 vs. 2.73, p=0.15); but CRs underestimate
      their influence in the residency program (1.94 vs. 2.34, p=0.002) and the
      emergency department (2.61 vs. 3.03, p=0.002). The majority of CRs (70%) and PDs
      (77%) report participating in an extramural training program, and those CRs who
      participated in training felt more prepared for their job duties (2.26 vs. 2.73;
      p=0.03). CONCLUSION: EM CRs feel they have appropriate job responsibility but
      believe they are less influential in program and department administration than
      PD respondents. Extramural training programs for incoming CRs are widely used and
      felt to be helpful.

PMID- 20823958
TI  - The association between money and opinion in academic emergency medicine.
AB  - OBJECTIVES: Financial conflicts of interest have come under increasing scrutiny
      in medicine, but their impact has not been quantified. Our objective was to use
      the results of a national survey of academic emergency medicine (EM) faculty to
      determine if an association between money and personal opinion exists. METHODS:
      We conducted a web-based survey of EM faculty. Opinion questions were analyzed
      with regard to whether the respondent had either 1) received research grant money
      or 2) received money from industry as a speaker, consultant, or advisor.
      Responses were unweighted, and tests of differences in proportions were made
      using Chi-squared tests, with p<0.05 set for significance. RESULTS: We received
      responses from 430 members; 98 (23%) received research grants from industry,
      while 145 (34%) reported fee-for-service money. Respondents with research money
      were more likely to be comfortable accepting gifts (40% vs. 29%) and acting as
      paid consultants (50% vs. 37%). They had a more favorable attitude with regard to
      societal interactions with industry and felt that industry-sponsored lectures
      could be fair and unbiased (52% vs. 29%). Faculty with fee-for-service money
      mirrored those with research money. They were also more likely to believe that
      industry-sponsored research produces fair and unbiased results (61% vs. 45%) and
      less likely to believe that honoraria biased speakers (49% vs. 69%). CONCLUSION:
      Accepting money for either service or research identified a distinct population
      defined by their opinions. Faculty engaged in industry-sponsored research
      benefitted socially (collaborations), academically (publications), and
      financially from the relationship.

PMID- 20823959
TI  - Identification and risk-stratification of problem alcohol drinkers with minor
      trauma in the emergency department.
AB  - BACKGROUND: Brief alcohol intervention may improve outcomes for injury patients
      with hazardous drinking but is less effective with increased severity of alcohol
      involvement. This study evaluated a brief method for detecting problem drinking
      in minor trauma patients and differentiating hazardous drinkers from those with
      more severe alcohol problems. METHODS: Subjects included 60 minor trauma patients
      in an academic urban emergency department (ED) who had consumed any amount of
      alcohol in the prior month. Screening and risk stratification involved the use of
      a heavy-drinking-day screening item and the Rapid Alcohol Problems Screen (RAPS).
      We compared the heavy-drinking-day item to past-month alcohol use, as obtained by
      validated self-reporting methods, and measured the percentage of carbohydrate
      deficient transferrin (%CDT) to assess the accuracy of self-reporting. The
      Alcohol Dependence Scale (ADS) was administered to gauge the severity of alcohol
      involvement and compared to the RAPS. RESULTS: Eighty percent of the subjects
      endorsed at least one heavy drinking day in the past year, and all patients who
      exceeded recommended weekly drinking limits endorsed at least one heavy drinking
      day. Among those with at least one heavy drinking day, 58% had a positive RAPS
      result. Persons with no heavy drinking days (n=12) had a median ADS of 0.5 (range
      0 to 3). RAPS-negative persons with heavy drinking days (n=20) had a median ADS
      of 2 (range 0 to 8). RAPS-positive persons with heavy drinking days (n=28) had a
      median ADS of 8 (range 1 to 43). CONCLUSION: A heavy-drinking-day item is useful
      for detecting hazardous drinking patterns, and the RAPS is useful for
      differentiating more problematic drinkers who may benefit from referral from
      those more likely to respond to a brief intervention. This represents a time
      sensitive approach for risk-stratifying non-abstinent injury patients prior to ED
      discharge.

PMID- 20823960
TI  - Sonographic scoring for operating room triage in trauma.
AB  - OBJECTIVE: The focused assessment with sonography for trauma (FAST) exam is a
      routine diagnostic adjunct in the initial assessment of blunt trauma victims but
      lacks the ability to reliably predict which patients require laparotomy.
      Physiologic data play a major role in decision making regarding the need for
      emergent laparotomy versus further diagnostic testing or observation. The need
      for laparotomy often influences the decision to transfer the patient to a trauma
      center. We set out to derive a simple scoring system using both ultrasound
      findings and immediately available physiologic data that would predict which
      patients require laparotomy. METHODS: We conducted a prospective observational
      study of victims of blunt trauma who presented to a Level 1 Trauma Center. We
      collected FAST findings, physiologic data, and lab values. A previously-developed
      ultrasound scoring system was applied to the FAST findings. Patients were
      followed to determine if they underwent laparotomy. We used logistic regression
      analysis to determine which variables correlated with laparotomy and developed a
      new scoring system. RESULTS: We enrolled a convenience sample of 1,393 patients.
      A simple scoring system (range 0-6) was developed that included both FAST
      findings and vital signs (heart rate and blood pressure). Patients with a score
      of 0 or 1 had a less than 1% chance of requiring laparotomy. CONCLUSION: The
      combination of FAST findings with vital signs in our scoring system predicted
      which victims of blunt trauma did not undergo laparotomy. Applying this to trauma
      patients who present to non-trauma centers could help prevent unnecessary patient
      transfers. This derivation set must be validated prior to use in patient care.

PMID- 20823961
TI  - Pain in the neck: the enigmatic presentation of an embedded acupuncture needle.

PMID- 20823962
TI  - Charcot foot? Charcot arthropathy caused by lisfranc fracture-dislocation in a
      diabetic.

PMID- 20823963
TI  - Radiographic Signs of Type 3A Schatzker Fracture of Lateral Tibial Plateau.

PMID- 20823964
TI  - An unusual facial impalement injury in a 75-year-old male.

PMID- 20823965
TI  - Chlorine gas: an evolving hazardous material threat and unconventional weapon.
AB  - Chlorine gas represents a hazardous material threat from industrial accidents and
      as a terrorist weapon. This review will summarize recent events involving
      chlorine disasters and its use by terrorists, discuss pre-hospital considerations
      and suggest strategies for the initial management for acute chlorine exposure
      events.

PMID- 20823966
TI  - Cocaine-associated seizures and incidence of status epilepticus.
AB  - OBJECTIVES: Acute complications from cocaine abuse are commonly treated in the
      emergency department (ED); one of the most consequential is status epilepticus.
      The incidence of this complication is not clearly defined in the prior literature
      on cocaine-associated sequelae. We evaluated the incidence of status epilepticus
      in patients with seizures secondary to suspected cocaine use. METHODS: We
      performed a retrospective multi-center study of patients with seizures resulting
      from cocaine use. We identified study subjects at 15 hospitals by record review
      and conducted a computer-assisted records search to identify patients with
      seizures for each institution over a four-year period. We selected subjects from
      this group on the basis of cocaine use and determined the occurrence of status
      epilepticus among them. Data were collected on each subject using a standardized
      data collection form. RESULTS: We evaluated 43 patients in the ED for cocaine
      associated seizures. Their age range was 17 to 54, with a mean age was 31 years;
      53% were male. Of 43 patients, 42 experienced a single tonic-clonic seizure and
      one developed status epilepticus. All patients had either a history of cocaine
      use or positive urine drug screen for cocaine. CONCLUSION: Despite reported cases
      of status epilepticus with cocaine-induced seizures, the incidence of this
      complication was unclear based on prior literature. This study shows that most
      cocaine-associated seizures are self-limited.

PMID- 20823967
TI  - Etomidate as an induction agent in septic patients: red flags or false alarms?
AB  - Despite its widespread use in North America and many other parts of the world,
      the safety of etomidate as an induction agent for rapid sequence intubation in
      septic patients is still debated. In this article, we evaluate the current
      literature on etomidate, review its clinical history, and discuss the controversy
      regarding its use, especially in sepsis. We address eight questions: (i) When did
      concern over the safety of etomidate first arise? (ii) What is the mechanism by
      which etomidate is thought to affect the adrenal axis? (iii) How has adrenal
      insufficiency in relation to etomidate use been defined or identified in the
      literature? (iv) What is the evidence that single dose etomidate is associated
      with subsequent adrenal-cortisol dysfunction? (v) What is the clinical
      significance of adrenal insufficiency or dysfunction associated with single dose
      etomidate, and where are the data that support or refute the contention that
      single-dose etomidate is associated with increased mortality or important post
      emergency department (ED) clinical outcomes? (vi) How should etomidate's effects
      in septic patients best be measured? (vii) What are alternative induction agents
      and what are the advantages and disadvantages of these agents relative to
      etomidate? (viii) What future work is needed to further clarify the
      characteristics of etomidate as it is currently used in patients with sepsis? We
      conclude that the observational nature of almost all available data suggesting
      adverse outcomes from etomidate does not support abandoning its use for rapid
      sequence induction. However, because we see a need to balance theoretical harms
      and benefits in the presence of data supporting the non-inferiority of
      alternative agents without similar theoretical risks associated with them, we
      suggest that the burden of proof to support continued widespread use may rest
      with the proponents of etomidate. We further suggest that practitioners become
      familiar with the use of more than one agent while awaiting further definitive
      data.

PMID- 20823968
TI  - A Pilot Study of the Performance Characteristics of the D-dimer in Presumed
      Sepsis.
AB  - OBJECTIVES: To determine if a sensitive D-dimer assay can exclude progression to
      organ dysfunction, death, and intensive care unit (ICU) admission in patients
      presenting to the emergency department (ED) with suspected infection, and if
      increasing levels of D-dimer are predictive of those end points. METHODS: The
      study took place at two academic EDs, both located in tertiary care hospitals.
      This was a prospective convenience sample of adult patients presenting with an
      infective process and at least two of four criteria for the Systemic Inflammatory
      Response Syndrome. We measured D-dimer levels in the participants and abstracted
      their records for the end points. Sensitivity and specificity were calculated and
      receiver operating characteristic analysis was performed to determine if a higher
      cutoff would have a greater specificity for our end points. RESULTS: We enrolled
      134 patients. Twelve were excluded from analysis (10 for lack of a D-dimer, one
      for recent surgery, and one for complete loss to follow up). Using the cutoff of
      0.4 established by our laboratories as positive, the D-dimer had a sensitivity of
      94% (CI95; 76-99) for organ dysfunction in the ED, 93% (72-99) for organ
      dysfunction at 48 hours, 93% (81-98) for ICU admission, and 100% (63-100) for 30
      day mortality. However, at this cutoff, specificity was not statistically
      significant. Significantly raising the cutoff for a positive resulted in a
      decrease in sensitivity but improved specificity. CONCLUSION: This study was
      limited by its nonconsecutive patient recruitment and sample size. A normal D
      dimer may exclude progression to organ dysfunction, ICU admission, and death and,
      at higher cutoff levels, could help risk stratify patients presenting to the ED
      with signs of sepsis.

PMID- 20823969
TI  - Incidence, radiographical features, and proposed mechanism for pneumocephalus
      from intravenous injection of air.
AB  - BACKGROUND: Pneumocephalus typically implies a traumatic breach in the meningeal
      layer or an intracranial gas-producing infection. Unexplained pneumocephalus on a
      head computed tomography (CT) in an emergency setting often compels emergency
      physicians to undertake aggressive evaluation and consultation. METHODS: In this
      paper, we report three cases of pneumocephalus that appear to result from
      retrograde injection of air through an intravenous (IV) catheter. We also
      performed a retrospective study to determine the incidence of presumed IV-induced
      pneumocephalus and etiologies of pneumocephalus in our emergency department (ED)
      population. RESULTS: The incidence of idiopathic and presumed IV-induced
      pneumocephalus was 0.034% among all head CTs ordered in the ED and 4.88% among
      cases of pneumocephalus seen in the ED. These cases are characterized clinically
      by the absence of signs and symptoms of pathologic pneumocephalus and
      radiographically by the distribution of air densities along the cranial venous
      system on head CTs. CONCLUSION: Idiopathic and presumed IV-induced pneumocephalus
      could be considered in the workup of ED patients with unexplained intracranial
      air on head CT if there are no findings of pathological causes for the
      pneumocephalus on history and physical examination and if the head CTs show a
      characteristic distribution of air limited to the cranial venous system.
      Knowledge of this clinical entity in the evaluation of ED patients with
      unexplained pneumocephalus can lead to more efficient emergency care and less
      patient anxiety.

PMID- 20823970
TI  - Catatonia associated with initiating paliperidone treatment.
AB  - We present a case of catatonia, which occurred shortly after starting a new
      antipsychotic, paliperidone, an active metabolite of risperidone. Catatonia may
      be caused by a variety of conditions, including metabolic, neurologic,
      psychiatric and toxic processes. Interestingly, risperidone, which has been
      thought to cause several cases of catatonia, has also been recommended as a
      potential treatment. We discuss potential mechanisms for causes of drug-induced
      catatonia as well as potential treatment options.

PMID- 20823971
TI  - Effect of hospital staff surge capacity on preparedness for a conventional mass
      casualty event.
AB  - OBJECTIVES: To assess current medical staffing levels within the Hospital
      Referral System in the City of Cape Town Metropolitan Municipality, South Africa,
      and analyze the surge capacity needs to prepare for the potential of a
      conventional mass casualty incident during a planned mass gathering. METHODS:
      Query of all available medical databases of both state employees and private
      medical personnel within the greater Cape Town area to determine current staffing
      levels and distribution of personnel across public and private domains. Analysis
      of the adequacy of available staff to manage a mass casualty incident. RESULTS:
      There are 594 advanced pre-hospital personnel in Cape Town (17/100,000
      population) and 142 basic pre-hospital personnel (4.6/100,000). The total number
      of hospital and clinic-based medical practitioners is 3097 (88.6/100,000),
      consisting of 1914 general physicians; 54.7/100,000 and 1183 specialist
      physicians; 33.8/100,000. Vacancy rates for all medical practitioners range from
      23.5% to 25.5%. This includes: nursing post vacancies (26%), basic emergency care
      practitioners (39.3%), advanced emergency care personnel (66.8%), pharmacy
      assistants (42.6%), and pharmacists (33.1%). CONCLUSION: There are sufficient
      numbers and types of personnel to provide the expected ordinary healthcare needs
      at mass gathering sites in Cape Town; however, qualified staff are likely
      insufficient to manage a concurrent mass casualty event. Considering that
      adequate correctly skilled and trained staff form the backbone of disaster surge
      capacity, it appears that Cape Town is currently under resourced to manage a mass
      casualty event. With the increasing size and frequency of mass gathering events
      worldwide, adequate disaster surge capacity is an issue of global relevance.

PMID- 20823973
TI  - Analysis of urobilinogen and urine bilirubin for intra-abdominal injury in blunt
      trauma patients.

PMID- 20823972
TI  - Ileocecal intussusception in the adult population: case series of two patients.
AB  - BACKGROUND: Intussusception is a condition found primarily in the pediatric
      population. In the adult population, however, intussusception is usually due to a
      pathological process, with a higher risk of bowel obstruction, vascular
      compromise, inflammatory changes, ischemia, and necrosis. Radiographic and
      sonographic evidence can aid in the diagnosis. Surgical intervention involving
      resection of affected bowel is the standard of care in adult cases of
      intussusception. CASE REPORTS: We present the case of a 21-year-old female who
      presented to the Emergency Department with diffuse cramping abdominal pain and
      distention. Workup revealed ileocecal intussusception, with a prior appendectomy
      scar serving as the lead point discovered during exploratory laparotomy. We also
      present the case of a 66-year-old male, who presented with one week of
      intermittent lower abdominal pain associated with several episodes of nausea and
      vomiting. Workup revealed ileocolic intussusception secondary to adenocarcinoma
      of the right colon, confirmed upon exploratory laparotomy with subsequent right
      hemicolectomy. CONCLUSION: In the adult population, intussusception is usually
      caused by a lead point, with subsequent telescoping of one part of the bowel into
      an adjacent segment. While intussusception can occur in any part of the bowel, it
      usually occurs between a freely moving segment and either a retroperitoneal or an
      adhesion-fixed segment. The etiology may be associated with pathological
      processes such as carcinoma or iatrogenic causes, such as scars or adhesions from
      prior surgeries. The cases presented here demonstrate important etiologies of
      abdominal pain in adult patients. Along with gynecological etiologies of lower
      quadrant abdominal pain in female patients, it is important for the emergency
      physician to expand the differential diagnosis to include other causes, such as
      intussusceptions, especially given the symptoms that could be associated with
      bowel obstruction.

PMID- 20823974
TI  - Cecal volvulus in adolescence presenting as recurring visits for abdominal pain.
AB  - Repeat visits to an emergency department (ED) within a short period of time for
      recurring or continuing abdominal pain should make physicians suspicious for
      relapsing or episodic disease processes. I present a case of a 17-year-old female
      with cecal volvulus found only after multiple ED visits.

PMID- 20823975
TI  - Toxic epidermal necrolysis from a cigarette burn.
AB  - Toxic epidermal necrolysis is a rare disease that is most often drug-induced but
      can be of idiopathic origin. We present a case that originated at the site of a
      cigarette burn to the forearm and review the key elements of physical exam
      findings and management of this life-threatening dermatological condition, which
      needs to be promptly recognized to decrease patient mortality.

PMID- 20823976
TI  - Retrobulbar hematoma from warfarin toxicity and the limitations of bedside ocular
      sonography.
AB  - The following case describes a 26-year-old female who presented to the emergency
      department with a nontrauamtic retrobulbar hematoma associated with warfarin
      toxicity. The application and limitations of focused bedside ocular sonography
      for this condition are discussed.

PMID- 20823977
TI  - Lyme carditis with transient complete heart block.

PMID- 20823978
TI  - "I Shouldn't Have Had Dessert..." A Moonflower Seed Ingestion.

PMID- 20823979
TI  - Parastomal intestinal evisceration.

PMID- 20823980
TI  - "Hanging" pelvic gallbladder simulating occult hip fracture versus appendicitis.

PMID- 20823981
TI  - Tibia-fibular Joint Dislocation.

PMID- 20823982
TI  - Hyperdense cerebral sinus vein thrombosis on computed tomography.

PMID- 20823983
TI  - Complicated orbital apex fracture in a child with a mild eye injury.

PMID- 20823984
TI  - Cholecysto-colonic Fistula Manifesting as Pneumobilia and Gastrointestinal Bleed.

PMID- 20823985
TI  - Intraosseous meningioma.

PMID- 20823986
TI  - Tension pneumothorax in child with mild viral symptoms.

PMID- 20823987
TI  - Ultrasound diagnosis of acute neck pain and swelling.

PMID- 20823988
TI  - Neonate with abdominal lump and anuria.

PMID- 20823989
TI  - Molar pregnancy.

PMID- 20823990
TI  - Clinically Oriented Research in Transfusion Medicine.

PMID- 20823991
TI  - Blood Donors on Medication - an Approach to Minimize Drug Burden for Recipients
      of Blood Products and to Limit Deferral of Donors.
AB  - BACKGROUND: Blood products derived from donors on medication can contain drugs
      which might pose a risk for the recipients or influence the quality of the
      product itself. MATERIAL AND METHODS: To judge the eligibility of blood donors on
      medication, 4 drug classes have been formed with respect to their pharmacological
      properties, and blood products have been divided in accordance with their single
      donor plasma contents. RESULTS: For drugs with dose-dependent pharmacodynamics,
      no deferral periods are necessary for donation of blood products containing less
      than 50 ml single-donor plasma for application to adults. Waiting periods of
      t(max) + 5 t(1/2) were calculated for the other blood products. Teratogenic drugs
      do not require special considerations (exception: retinoids, thalidomide and
      lenalidomide, dutasteride or finasteride with waiting periods for all blood
      products). A deferral period of t(max) + 24 t(1/2) is proposed for every blood
      product from blood donors on genotoxic drugs. Drugs without systemic effects can
      be neglected. Irreversible inhibitors of platelet function cause a 10-day waiting
      period if production of platelet concentrates is intended. CONCLUSION: Donors on
      medication are allowed to donate blood for blood products containing less than 50
      ml plasma of a single donor, like red blood cell concentrates, for the use in
      adults without deferral periods, except those taking retinoids, thalidomide,
      lenalidomide, dutasteride, finasteride, or genotoxic drugs.

PMID- 20823992
TI  - Evaluation of White Blood Cell- and Platelet-Derived Cytokine Accumulation in
      MIRASOL-PRT-Treated Platelets.
AB  - BACKGROUND: Soluble mediators in platelet concentrates (PCs) released from
      contaminating white blood cells (WBCs) and platelets (PLTs) themselves are
      supposed to promote allergic and non-hemolytic febrile transfusion reactions in
      the recipient. Pathogen reduction technologies (PRTs) prevent replication and
      proliferation of pathogens as well as of WBCs, and may reduce cytokine
      accumulation in PCs during storage and prevent adverse events after PLT
      transfusion. On the other hand, such treatments may also lead to increased
      cytokine production by stimulation of WBCs or PLTs due to the photochemical or
      photodynamical process itself. MATERIAL AND METHODS: 12 triple-dose PLT apheresis
      collections were leukoreduced by the process-controlled leukoreduction system of
      the Trima Accel machine and split into 3 units undergoing Mirasol-PRT treatment
      (M) or gamma irradiation (X) or remaining untreated (C). During storage for up to
      7 days, PLT activation, WBC-derived Th-1/2, and inflammatory as well as PLT
      derived cytokines were measured by cytometric bead array and enzymelinked
      immunosorbent assay, respectively. RESULTS: Independent of treatment, all PLT
      products exhibited low levels of WBC-associated cytokines near or below assay
      detection limits. WBC-associated cytokines were not elevated by Mirasol-PRT
      treatment. PLT-derived cytokines were detected at higher levels and increased
      significantly during storage in all units. Most likely due to higher PLT
      activation, M units showed significantly higher levels of PLT-derived cytokines
      compared to untreated and gamma-irradiated units on day 5 of storage. CONCLUSION:
      In all PCs, PLTs themselves were the main source of cytokine release. Mirasol-PRT
      treatment was associated with a significantly increased PLT activation and
      accumulation of PLT-derived cytokines during storage, without affecting WBC
      derived cytokines relative to controls.

PMID- 20823993
TI  - Thrombin Generation Capacity of Methylene Blue-Treated Plasma Prepared by the
      Theraflex MB Plasma System.
AB  - BACKGROUND: Methylene blue (MB) / light treatment is a well-known procedure for
      the inactivation of pathogens in fresh frozen plasma (FFP). Aim of the current
      study was to investigate the thrombin generation (TG) characteristics and quality
      of MB plasma prepared by the Theraflex MB Plasma System. METHODS: Single donor
      plasma units (n = 18) were MB/light-treated, with sampling before and after
      processing. Preparation included leukocyte depletion, addition of MB pill prior
      to illumination, and depletion of MB and photoproducts by filtration. Different
      plasma parameters and TG were measured. TG additionally was determined in
      solvent/detergent plasma (n = 8). RESULTS: MB/light treatment significantly
      affected factors V, VIII and XI, which were decreased by 9-18%. While the antigen
      level was not affected, fibrinogen according to Clauss was decreased by 7%,
      correlating with a 12% prolongation of TT and RT. The total amount of free
      thrombin generated, given as 'area under the curve' (AUC), was comparable for
      untreated (93 +/- 18% of normal plasma) and MB/light-treated plasma (95 +/- 20%).
      Also peak thrombin concentration was not significantly affected by treatment (94
      +/- 11% (untreated) vs. 96 +/- 12% (treated)). The 'time to peak' value (TTP) was
      105% of normal plasma for untreated FFP and 89% for MB-treated plasma.
      CONCLUSION: For plasma treated with the Theraflex MB Plasma System no profound
      influence of MB/ light treatment on the characteristics of thrombin generation
      was detected. In concordance with data from the literature, coagulation factors
      V, VIII and XI were decreased due to MB/ light treatment. Decrease was less than
      20%.

PMID- 20823994
TI  - Rhabdomyolysis in a Healthy Peripheral Blood Stem Cell Donor following
      Mobilization with Filgrastim.
AB  - BACKGROUND: Although granulocyte colony stimulating factor (G-CSF) mobilization
      is generally well tolerated by healthy donors, there is also a wide spectrum of
      adverse events associated with it. Among these events, rhabdomyolysis in
      peripheral blood stem cell (PBSC) donors is very rare. In this paper, we present
      a first case of rhabdomyolysis after administration of filgrastim for PBSC
      mobilization. CASE REPORT: A 6-year-old donor received 10 mug/kg/day filgrastim
      subcutaneously for 5 days. On the 3rd day of filgrastim, the donor complained of
      bone pain; a single dose of paracetamol (250 mg) was given to relieve pain. On
      the 4th day, she complained of bone pain, myalgia, and vomiting. On laboratory
      analysis, serum creatine phosphokinase was 1,095 U/l (40-226 U/l), LDH 312 U/l
      (100-190 U/l), aspartate aminotransferase 85 U/l (0-40 U/l), potassium 3.3 mmol/l
      (3.6-5.1 mmol/l). Urine myoglobin was 110 ng/ml (<5 ng/ml). Rhabdomyolysis was
      suspected on clinical and laboratory findings. Clinical manifestations regressed
      and the laboratory results returned to normal within three days after
      intravenously forced diuresis and potassium replacement. Stem cells were
      successfully harvested from peripheral blood on the 5th day of G-CSF therapy.
      CONCLUSION: Rhabdomyolysis is a rare but important adverse effect of G-CSF.
      Allogeneic PBSC donors should be closely monitored with regard to rhabdomyolysis
      after G-CSF administration in the mobilization setting.

PMID- 20823995
TI  - Successful Use of Factor VIII Concentrate and Fresh Frozen Plasma for Four Dental
      Extractions in an Individual with Combined Factor V and VIII Deficiency.
AB  - BACKGROUND: Combined factor V and VIII deficiency (CF5F8D) is a rare autosomal
      recessive disorder, with an estimated prevalence of about 1:100,000 in the Jewish
      population. Affected individuals have between 5 and 30% of normal levels of
      factor V and VIII, whereas the levels of other plasma proteins are not altered.
      This bleeding disorder has been treated by replacement therapy with plasma
      infusion and FVIII concentrate as source of factor V and VIII, respectively,
      depending on the severity of the haemorrhage. CASE REPORT: The individual with
      CF5F8D was a 22-year-old man with APTT of 51 s (control 33 s), PT of 27 s
      (control 12 s), factor V of 13%, and factor VIII of 21%. He had four untreatable
      carious teeth, including the maxillary first premolars and the mandibular first
      and second right molar. Factor VIII concentrate infusion began 12 h before the
      first dental extraction procedure and was continued in 8 h intervals. Moreover,
      10 ml/kg of fresh frozen plasma were given for compensating factor V deficiency.
      No remarkable haemorrhage occurred during and after the procedures. The levels of
      factor V and VIII post procedures were 64 and 75%, respectively. CONCLUSION: It
      seems that plasma levels of 6075% for both factor V and VIII may be sufficient
      for major dental procedures.

PMID- 20823996
TI  - Anticoagulation in a Neurosurgical Patient with Heparin-Induced Thrombocytopenia
      Type II with Argatroban and Fondaparinux after Clipping of an Intracranial
      Aneurysm.
AB  - BACKGROUND: Therapeutic anticoagulation in patients after a major neurosurgical
      procedure remains critical because of the risk of a major intracranial bleed.
      Novel drugs could play a beneficial role in this setting. CASE REPORT: We
      describe a patient with heparin-induced thrombocytopenia type II and pulmonary
      embolism who was anticoagulated with argatroban and, later, with fondaparinux. No
      intracranial bleeding was detected when anticoagulation was performed with
      argatroban and, later, fondaparinux. CONCLUSION: Both substances could have
      therapeutic potential in this context.

PMID- 20823997
TI  - Still in Focus: Assessment of Blood-Borne Pathogens.

PMID- 20823999
TI  - The Fourth Annual Meeting of the International Network for Pediatric Hemophilia:
      Current Challenges and Recommendations in the Clinical Care of Children with
      Hemophilia.
AB  - The International Network for Pediatric Hemophilia (INPH) comprises a group of
      physicians committed to the unique care of and challenges facing pediatric
      hemophilia patients. By collaborating on an international level, extensive
      experience can be shared on current practice, new trends can be discussed and
      scientifically valid studies can be developed and performed. The three overall
      objectives of the group (scientific progress, education and networking) are
      achieved at each annual meeting starting with a round table on the members'
      current research and clinical activities, project reports of INPH study
      initiatives, followed by invited educational presentations and interactive
      discussions. The meetings close with proposals of new projects, future directions
      of the group and concluding remarks. The Fourth Annual INPH meeting, held in 2009
      in Boston, MA, USA, focused on inhibitor development and hemophilic arthropathy
      in the clinical care of children with hemophilia.

PMID- 20823998
TI  - Markers of Blood Cell Activation and Complement Activation in Factor VIII and von
      Willebrand Factor Concentrates.
AB  - BACKGROUND: Preparations of commercially available clotting factor VIII are
      complex protein mixtures. Most of them contain either von Willebrand factor or
      human serum albumin as stabilizers. The aim of the study was to quantify further
      proteins in twelve concentrates either of recombinant origin or derived from
      human plasma. METHODS: Proteins were separated by two-dimensional polyacrylamide
      gel electrophoresis (2D-PAGE). Some proteins were quantified by ELISA. RESULTS:
      Recombinant clotting factor preparations showed fewer protein spots in the 2D
      PAGE, than plasma-derived preparations. Proteins identified in some of the plasma
      derived concentrates included up to 90 ng/IU of the anaphylatoxin C3a, up to 40
      ng/IU of the platelet a-granule protein thrombospondin-1, up to 0.85 ng/IU of the
      platelet a-granule protein platelet factor 4, 3.5 ng/IU myeloperoxidase secreted
      by leukocytes and up to 0.05 ng/IU of the leukocyte-secreted protein a-defensin.
      The protein content differed between concentrates from different manufacturers.
      CONCLUSIONS: The origin of the plasma used to prepare the factor concentrates
      might influence the protein impurities in these products. It is unknown whether
      the impurities observed have long-term consequences for chronic inflammatory
      conditions.

PMID- 20824000
TI  - Treatment Options in ErbB2 (HER2)-Overexpressing Breast Cancer.

PMID- 20824001
TI  - Development of Targeted Therapies in ErbB2-Positive Breast Cancer.

PMID- 20824002
TI  - Clinical Experience with Lapatinib in Patients with ErbB2-Overexpressing
      Metastatic Breast Cancer.

PMID- 20824003
TI  - Practical Management Recommendations for Anti-ErbB2 Therapy with Lapatinib.

PMID- 20824004
TI  - Adjuvant and Neoadjuvant Therapy with Lapatinib in ErbB2-Overexpressing Breast
      Cancer.

PMID- 20824005
TI  - Perspectives on Breast Cancer Management: Tailoring Treatment to the Individual
      Patient.

PMID- 20824006
TI  - The Role of uPA and uPA Inhibitors in Breast Cancer.

PMID- 20824007
TI  - Assessment of Urokinase-Type Plasminogen Activator and Its Inhibitor PAI-1 in
      Breast Cancer Tissue: Historical Aspects and Future Prospects.

PMID- 20824009
TI  - uPAR and HER2 Genes Are Usually Co-Amplified in Individual Breast Cancer Cells
      from Blood and Tissues.

PMID- 20824008
TI  - Prospective Biomarker Trials Chemo N0 and NNBC-3 Europe Validate the Clinical
      Utility of Invasion Markers uPA and PAI-1 in Node-Negative Breast Cancer.

PMID- 20824010
TI  - The Oral Serine Protease Inhibitor WX-671 - First Experience in Patients with
      Advanced Head and Neck Carcinoma.

PMID- 20824011
TI  - Experience in Phase I Trials and an Upcoming Phase II Study with uPA Inhibitors
      in Metastatic Breast Cancer.

PMID- 20824012
TI  - Breast Cancer in Developing Countries: Challenges for Multidisciplinary Care.

PMID- 20824013
TI  - Breast Cancer in Low and Middle Income Countries: How Can Guidelines Best Be
      Disseminated and Implemented?

PMID- 20824014
TI  - Breast Cancer in Countries of Limited Resources.
AB  - For 2010, the annual incidence of breast cancer is estimated to increase from now
      1.15 Mio to 1.5 Mio new cases per year. The increase is mainly seen in low and
      middle income countries. Resource limitations in means of finance, personnel,
      infrastructure, and by political instability are tremendous. Currently, little
      attention is paid to breast care in low-resource settings due to other health
      priorities. However, with increasing life expectancy and reduction of mortality
      due to infectious diseases, more people are confronted with non-communicable
      diseases, and the topic of cancer in developing countries will emerge more and
      more. Specific guidelines for breast cancer were given by the Global Breast
      Health Initiative differentiating according to available resources in different
      settings. From awareness in public and health care facilities to obtaining the
      diagnosis, deciding on strategies of treatment, and putting strategies into
      practice - all these obstacles differ substantially in developed and developing
      countries. Further research is essential to meet the challenge of breast cancer
      worldwide in the coming years.

PMID- 20824015
TI  - Practical Applications for Clinical Breast Examination (CBE) and Breast Self
      Examination (BSE) in Screening and Early Detection of Breast Cancer.
AB  - The background and preliminary results in terms of stage distribution are given
      for a trial of Clinical Breast Examination and the teaching of Breast Self
      Examination in Cairo, Egypt. A stage shift towards early diagnosis appears to
      have been achieved. This has encouraged the development of similar projects in
      other middle income developing countries.

PMID- 20824016
TI  - Breast Cancer Care in India: The Current Scenario and the Challenges for the
      Future.
AB  - The incidence of breast cancer is low in India, but rising. Breast cancer is the
      commonest cancer of urban Indian women and the second commonest in the rural
      women. Owing to the lack of awareness of this disease and in absence of a breast
      cancer screening program, the majority of breast cancers are diagnosed at a
      relatively advanced stage. The quality of care available for breast cancer
      patients varies widely according to where the patient is treated. Although there
      are some centers of excellence providing multimodality protocol-based treatment
      at par with the best anywhere in the world, the vast majority of breast cancer
      patients undergo inadequate and inappropriate treatment due to lack of high
      quality infrastructure and sometimes skills, and above all financial resources.
      The recent emphasis on health education, early diagnosis of cancers, and more
      public facilities for cancer treatment are expected to bring about the much
      needed improvement in breast cancer care in India.

PMID- 20824017
TI  - Pilot Implementation of Breast Cancer Early Detection Programs in Colombia.
AB  - Breast cancer is increasing in developing countries, and Colombia has a double
      burden from cervical and breast cancer. Suitable guidelines for breast cancer
      early detection are needed, and the Breast Health Global Initiative provides a
      favorable framework for breast cancer control in low resource nations. The
      Colombian National Cancer Institute developed evidence-based guidelines for
      breast cancer early detection in which coordinated early detection in symptomatic
      women and hospital-based screening in women aged 50-69 are recommended. A pilot
      project to evaluate programmatic approaches (opportunistic screening) was
      designed, and it is expected that organized hospital-based screening for breast
      cancer will represent a move towards population-based screening in the near
      future in accordance with country specific conditions.

PMID- 20824018
TI  - A Pilot Project to Develop Checklist-Based Recommendations on the Requirements
      for Clinical Cancer Research Centers in Countries with Limited Resources.
AB  - Clinical studies are the only controlled way of comparing a new treatment to
      existing standards. Unfortunately, less than 5% of patients in developed
      countries are enrolled in clinical trials, thus strongly limiting the possibility
      of answering important clinical questions. Large numbers of cancer patients are
      treated in countries with limited resources (CLR). Here, cancer centers that are
      able to provide good standard of care are capable of contributing by enrolling
      large numbers of eligible patients into clinical trials. We present a pilot
      project aimed at developing a set of checklists that include all elements of
      infrastructure, equipment, staff, and training that a center should possess in
      order to enroll patients into phase II, III, and IV clinical trials. These
      elements will be stratified in an incremental list to contain essential,
      desirable, and optional items. Also, requirements for staffing and training of
      research staff will be developed. The development of a continuous audit program
      will be proposed to ensure quality control, and each potential trial center will
      undergo an initial audit to evaluate its suitability. The checklists may also
      serve as a guide for centers wishing to participate in clinical trials. The
      ultimate goal of this project is to increase the number of trial centers in CLR
      for the benefit of patients, science, and society in general.

PMID- 20824019
TI  - Delay in seeking medical advice and late presentation of female breast cancer
      patients in most of the world. Could we make changes? The experience of 23 years
      in port said, egypt.
AB  - BACKGROUND: In the low and middle income countries delays in seeking
      consultation, late presentation, and the availability of breast cancer management
      for all patients, represent major challenges. MATERIALS AND METHODS: The delay in
      seeking medical advice and the pathological tumor size of females breast cancer
      patients in the years 2004-2006 in Port Said, Egypt were studied and compared
      with previous studies by Elzawawy published since 1987. We report the progress of
      availability of breast cancer management from 1984 until the end of June 2007.
      RESULTS: There was a decline in advanced cases. Mean time from a symptom to
      seeking advice was 18, 8, 3, and 1 month respectively in 1987, 1989, 1999, and
      2007. Since 1984, facilities for all lines of comprehensive management have been
      established, interconnected, and been made accessible for all citizens, free of
      charge. CONCLUSION: Breast cancer problems are characterized by a certain multi
      complexity. There is no one single cause for late cases. However, we report that
      the availability of cancer management facilities could lead to earlier
      presentation. Early detection programs would be frustrating for both patients and
      health authorities if patients were unable to afford accessible treatment.

PMID- 20824020
TI  - Clinical Relevance of CYP2D6 Genetics for Tamoxifen Response in Breast Cancer.
AB  - Tamoxifen is a standard endocrine therapy for the prevention and treatment of
      steroid hormone receptor-positive breast cancer. Tamoxifen requires enzymatic
      activation by CYP 450 enzymes for the formation of clinically relevant
      metabolites, 4-OH-tamoxifen and endoxifen, which both have a greater affinity to
      the estrogen receptor and ability to inhibit cell proliferation when compared to
      the parent drug. CYP2D6 is the key enzyme in this biotransformation, and recent
      mechanistic, pharmacologic, and clinical pharmacogenetic evidence suggests that
      genetic variants and drug interaction by CYP2D6 inhibitors influence plasma
      concentrations of active tamoxifen metabolites and outcome of patients treated
      with adjuvant tamoxifen. Particularly, non-functional (poor metabolizer) and
      severely impaired (intermediate metabolizer) CYP2D6 variants are associated with
      higher recurrence rates. Accordingly, CYP2D6 genotyping prior to treatment for
      prediction of metabolizer status and outcome may open new avenues for the
      individualization of endocrine treatment choice and benefit. Moreover, strong
      CYP2D6 inhibitors such as the selective serotonin reuptake inhibitor paroxetine
      should be avoided as co-medication.

PMID- 20824021
TI  - Bilateral Nonsynchronous Male Breast Cancer: Two Case Reports.
AB  - SUMMARY: BACKGROUND: Bilateral male breast cancer (MBC) is relatively rare. CASE
      REPORTS: We report 2 bilateral nonsynchronous MBC cases. Second cancers developed
      during endocrine therapy with selective estrogen receptor modulators (SERM) after
      the initial surgeries. Since their second surgeries, both patients continued
      treatment with another SERM, because their second cancers were also hormone
      receptor-positive. We discuss the endocrine therapy in men based on a review of
      the literature. CONCLUSIONS: Adequate treatments for early MBC are still
      controversial. Aromatase inhibitors (AI) are not as effective in men as in women.
      We consider the higher androgen levels in men to be a major reason for AI not
      being as effective as expected, i.e. the hormonal environment is very different
      from that in women. Thus, different approaches are needed for MBC. With further
      investigation, it is hoped that methods of achieving maximal AI efficacy for MBC
      will be established.

PMID- 20824022
TI  - Knowledge, Attitudes, and Behaviors of Female Teachers Related to Breast Cancer
      and Breast Examination in Southern Turkey.
AB  - SUMMARY: BACKGROUND: The aim of this study was to investigate the knowledge,
      attitudes, and behaviors of female teachers related to breast cancer in Southern
      Turkey. MATERIALS AND METHODS: There are almost 5,000 female teachers working in
      Hatay, Turkey, and we aimed to reach 10% of this population. Our questionnaire
      consisted of 14 questions about personal information, 14 questions about
      knowledge related to breast cancer, and 14 questions about attitudes and
      behaviors of teachers. RESULTS: In all, 490 female teachers participated in the
      study. The mean age was 34.6 years, and most were married (77.1%). 62.9% of
      participants reported to have insufficient knowledge about breast cancer. The
      source of information was newspaper/TV in 84.6%, and medical health care
      providers in 22.8%. While all of the participants think that early diagnosis of
      breast cancer is important; 19% think personal hygiene is protective against
      breast cancer. Among all the participants, 53.7% have never practiced breast self
      examination (BSE). Of those who practice BSE; 80.6% practice it as they remember,
      12.5% practice it once a month. 38.4% of these learned BSE from a doctor, and
      38.0% from TV. The reason for not practicing BSE was underestimation in 46.7% and
      lack of knowledge in 37.9%. 152 participants had a clinical breast examination
      (CBE) done, and 145 of these had it done by an expert doctor. A total of 86
      participants had undergone mammography, while 67 of the over-40-year-old group
      had not. CONCLUSION: 3/5 of the female teachers think that they do not have
      enough knowledge related to breast cancer. More than half of them do not practice
      BSE, and only 12.5% of them practice BSE regularly.

PMID- 20824023
TI  - Endocrine Therapy - What Else?

PMID- 20824024
TI  - Neoadjuvant Endocrine Therapy in Breast Cancer.
AB  - Women who suffer from large or locally advanced malignant breast tumors are now
      commonly treated with preoperative ('neoadjuvant') systemic therapy to improve
      surgical outcomes and to raise the chances for breast-conserving therapy (BCT).
      Until recently, chemotherapy was the treatment of choice, and primary systemic
      endocrine treatment was restricted to medically frail or older women with
      receptor-positive breast cancer. The development of modern aromatase inhibitors
      (Als) and their subsequent clinical evaluation in neoadjuvant trials now provides
      us with an alternative to chemotherapy that is thought to be equally effective,
      yet considerably better tolerated. Several large prospective trials have compared
      tamoxifen with the non-steroidal AIs letrozole and anastrozole and the steroidal
      Al exemestane, with improved outcomes for all AIs in terms of tumor remission and
      rate of BCT. A number of predictive biomarkers now also allow us to identify
      those tumors that most likely respond to a certain endocrine regimen.

PMID- 20824025
TI  - Adjuvant Endocrine Therapy in Premenopausal Patients.
AB  - Endocrine adjuvant therapy is the best-described molecular targeted treatment and
      should therefore be used for all patients with endocrine-responsive breast
      cancer. Ta-moxifen for 5 years is standard of care and has proven efficacy in
      premenopausal patients. The combination of tamoxifen with ovarian function
      suppression and/or chemotherapy has been extensively tested, and some
      controversial approaches are used in clinical practice. Cessation or suppression
      of ovarian function appears to be beneficial for premenopausal patients.
      Particularly for premenopausal women with highly endocrine-responsive disease
      and/or low risk for relapse, the additional benefit of cytotoxic chemotherapy may
      be minor or nonexistent. While the use aromatase inhibitors is investigated in
      clinical trials, their application outside an academic trial setting cannot be
      recommended based on first available results. In contrast, the use of adjuvant
      bispho-sphonates may offer another strategy of further improving clinical
      outcomes in this important patient subgroup.

PMID- 20824026
TI  - Adjuvant Endocrine Therapy in Early Postmenopausal Breast Cancer.
AB  - Five years of adjuvant tamoxifen treatment has been the gold standard for women
      with early hormone-responsive breast cancer. Results from two large phase III,
      adjuvant studies have indicated that the third-generation aro-matase inhibitors
      (AIs) letrozole and anastrozole offer greater protection against recurrence than
      tamoxifen in upfront substitution strategies in the first 5 years. Similarly,
      changeover to an AI (exemestane or anastrozole) after 2-3 years of tamoxifen has
      been more efficient to prevent recurrence than 5 years of tamoxifen. Most early
      breast cancer recurrences occur 5 or more years after surgery. Letrozole has been
      shown to offer greater protection against recurrence than placebo in the 5 years
      after a standard course of tamoxifen. The optimal adjuvant use (duration and
      sequencing) of AIs requires further investigation. Safety implications of
      treatment with these AIs for 5 years or more are closely monitored. The
      anticipated effects of estrogen deprivation on bone health may be treatable with
      bisphosphonates. Effects on the cardiovascular system, and other estrogen
      sensitive systems such as the central nervous system, are currently examined. The
      AIs letrozole, anastrozole, and ex-emestane have recently replaced tamoxifen as
      the recommended adjuvant endocrine therapy, on the basis of greater efficacy and
      better tolerability.

PMID- 20824028
TI  - Bendamustine in Metastatic Breast Cancer: An Old Drug in New Design.
AB  - The goal of treatment for patients with advanced breast cancer is to prolong
      survival, control symptoms, and reduce disease-related complications. Despite the
      introduction of many cytotoxic agents during the past decade, only modest
      improvement in survival in metastatic breast cancer has been achieved. In order
      to improve this situation, new cytotoxic drugs as well as molecule-targeted
      agents are now under investigation. Bendamustine is a bifunctional alkylating
      agent with cytotoxic activity against several types of solid tumors. In the
      search for new anthracycline-free combinations, taxanes and alkylating agents
      might be worth investigating, in order to reduce cardiac toxicity. In this
      article, we reviewed the latest information regarding antitumor activity,
      toxicity, pharmacokinetics, and clinical application of bendamustine as a
      cytotoxic agent in metastatic breast cancer.

PMID- 20824027
TI  - The Role of Androgens in Normal and Malignant Breast Tissue.
AB  - Androgens, like estrogens, can be synthesized in the breast. As both active
      androgens and their corresponding receptors are present in breast tissue, we
      conclude that they play a role in breast physiology. This is supported by the
      fact that insufficient androgen production or sensitivity results in the
      development of gynecomastia. Complete androgen insensitivity due to receptor
      defects leads to normal female breast development in these XY women. While breast
      development is completely inhibited by male testosterone levels, partial but not
      total degradation of a developed breast by androgen treatment appears to be
      possible. Breast cancer in early stages seems to fulfill the prerequisites of
      androgen responsiveness. Androgen treatment of advanced breast cancer has shown
      similar effectiveness as anti-estrogen or estrogen-ablative therapy, but also
      considerable side effects. It has been speculated that the use of selective
      androgen modulators (SARMs), either alone or preferably in addition to anti
      estrogens or aromatase inhibitors, may be a promising alternative to current
      therapy modalities in hormone-dependent breast cancer. In addition, future
      studies on the use of SARMs in prophylactic settings seem to be justified.

PMID- 20824029
TI  - Critical Appraisal of Randomized Clinical Trials: Can We Have Faith in the
      Conclusions?
AB  - Randomized clinical trials (RCTs) are the most appropriate research design for
      studying the effectiveness of a specific intervention. Its results are considered
      as the highest 'level of evidence'. Published reports on RCTs have already
      succeeded in a peer review process, but still there can be undetected major
      deficiencies of the study that may question the reported outcome. It is still up
      to the readers to assess the quality of publications and to question if the
      published results apply to their patients. The major points of such a critical
      appraisal process are reviewed and discussed with a focus on breast cancer
      studies.

PMID- 20824030
TI  - Vacuum-Sealing as a Treatment Option for Severe Anthracycline Extravasation in a
      Breast Cancer Patient.
AB  - BACKGROUND: Compared to peripheral venous access, central lines greatly reduce
      the incidence of cytotoxic extravasation. Although implantable vascular systems
      are widely used in oncology, extended extravasation lesions in cancer patients
      remain complicated. PATIENT AND METHOD: A 67-year-old female breast cancer
      patient suffered from an extended lesion of a catheter port extravasation. A
      vacuum-sealing therapy was initiated to accelerate the healing of the
      anthracycline-induced wound. RESULT: The vacuum-sealing technique allowed a fast
      and successful treatment of the extravasation lesion. CONCLUSION: Due to the
      myelosuppressive chemotherapy regimen, the risk of wound infections and prolonged
      healing processes is increased in cancer patients. Moreover, disruption or
      cancellation of anticancer therapies worsens the patients' prognosis. To
      attenuate these complications the vacuum-sealing technique should be considered
      in wound management concepts.

PMID- 20824031
TI  - Psychooncologic Aspects of Breast Cancer.
AB  - Around one third of all patients reveal signs of stress disorder and adaptation
      difficulties following breast cancer or during the course of the illness, often
      manifested clinically as fear and depression. Supportive treatment should be made
      available to all patients in the form of psycho-educative group sessions
      introducing information and assistance to help overcome the illness. The
      indication for extensive treatment, e.g. psychotherapy, can be deduced from the
      somatopsychic disorders presented. Individual or group therapy will be offered to
      the patient corresponding to her diagnostics and motivation. The aim of therapy
      should be discussed openly with the patient, that is, an improvement in the
      quality of life and the possibility to overcome the situation. In general, the
      various intervention programmes have proved to be beneficial for patients with
      cancer. These include relaxation therapy and stress management as well as
      behavioural therapy and supportive psychotherapy. Patients have high expectations
      of the therapy offered and this should be taken into careful consideration by all
      physicians, psychologists and others responsible for administering treatment. The
      aim of this work is mainly to present the clinical experience gained in a breast
      centre.

PMID- 20824032
TI  - Trastuzumab Improves the Efficacy of Chemotherapy in Breast Cancer Treatment
      beyond Progression.

PMID- 20824033
TI  - Breast Cancer in Special Situations.

PMID- 20824034
TI  - Carcinoma of Unknown Primary - an Orphan Disease?
AB  - Carcinoma of unknown primary (CUP) is an intriguing clinical finding that is
      defined as biopsy-proven metastasis from a malignancy in the absence of an
      identifiable primary site after a complete clinical work-up. CUP is a relatively
      common clinical entity, accounting for approximately 3-5% of all cancer
      diagnoses, and consists of a heterogeneous group of tumors that have acquired the
      capacity to metastasize before the development of a clinically evident primary
      lesion. Notable advances have been made over the past years in the treatment of
      well-defined clinical subgroups of CUP, such as women with peritoneal
      carcinomatosis and young adults with poorly differentiated carcinomas of midline
      distribution, but for the majority of patients, the prognosis still remains poor.
      In this review, we highlight recent advances in the diagnosis and treatment of
      patients with CUP syndrome, and emphasize the importance of identifying several
      favorable subsets of CUP, amenable to specific treatment options. In addition, we
      will point out novel diagnostic and therapeutic approaches which will hopefully
      improve both our understanding and the prognosis of this more or less neglected
      disease.

PMID- 20824035
TI  - New Therapeutic Options for Breast Cancer during Pregnancy.
AB  - National and international guidelines for pregnant breast cancer patients
      recommend to treat pregnant patients as closely as possible to the standards for
      non-pregnant patients. Therefore, new treatment options like sentinel lymph node
      biopsy or taxane-based chemotherapy have to be carefully checked for their
      possible implementation even for pregnant patients. These patients need to be
      treated in a breast cancer center where a multidisciplinary team is ready to
      support the patient and her family and to serve her with the best up-to-date
      treatment for mother and child.

PMID- 20824036
TI  - Mammography Screening and Treatment of Breast Cancer in the Elderly.
AB  - Breast cancer patients of an advanced age will suffer from ailments related to
      both senescence and cancer. Some will have been denied access to screening
      programmes and will present with an advanced disease. Many will need the
      expertise of the geriatrician and the oncologist who will participate in specific
      case discussions to look at social and medical issues that will affect the
      treatment plan (with questions regarding surgery, radiation, drug therapy,
      rehabilitation, supportive care, and palliative care often intertwined). This
      paper reviews recommendations by the International Society of Geriatric Oncology
      (SIOG) task force which recently assessed the available evidence on breast cancer
      in elderly individuals, and provided evidence-based recommendations for the
      diagnosis and treatment of breast cancer in such individuals. Recommendations on
      the topics of screening, surgery, radiotherapy, (neo)adjuvant hormone treatment,
      and chemotherapy, and on metastatic disease have been given. Oncologists are now
      learning to take into account the physiological age of their patient, which is
      the reflection of a normal and sometimes abnormally accelerated loss of body
      reserves which is certainly related to chronological age but not precisely
      dictated by it. Understanding the biology of breast cancer will allow to
      optimally adapt the treatment of the elderly patient.

PMID- 20824037
TI  - Male Breast Cancer.
AB  - Breast cancer is a rare disease in men representing nearly 1% of the total breast
      cancer cases worldwide. Due to the low incidence, there are no randomized
      clinical studies giving information on the optimal diagnostics and therapy for
      male breast cancer patients. Therefore, treatment recommendations are derived
      from established guidelines for breast cancer in women. However, the lack of
      awareness of this disease leads to its detection at a later stage in men
      associated with a worse prognostic outcome. The gender-specific differences in
      breast cancer are among others related to the differing genetic and hormonal
      environment and the anatomic constitution in men. For example, males have a much
      higher percentage of hormone receptor-positive tumors but a significantly lower
      fraction of carcinomas overexpressing HER2. This review focuses on epidemiology,
      pathogenesis, and clinical findings of male breast cancer, and discusses current
      findings available to treat this disease. To optimize disease outcome and
      tolerability of treatment, these data should be considered to improve the
      therapeutic index of male breast cancer patients.

PMID- 20824038
TI  - Management of Rare Histological Types of Breast Tumours.
AB  - Breast tumours exhibit a wide range of morphological phenotypes, and specific
      histopathological types have particular prognostic and clinical characteristics.
      The management of uncommon premalignant and malignant lesions is often
      controversial due to the lack of large single-institution studies or randomised
      trials to define optimal treatments. In the era of frequent use of treatment
      guidelines, only a low level of evidence exists for the management of rare
      histological types of breast tumours. This review is divided into two parts:
      Firstly, the favourable histological subtypes like tubular, mucinous, medullary
      breast cancers, and phyllodes tumour (benign, borderline, and malignant) are
      discussed. The prognosis of these selected lesions is believed to be better than
      for invasive ductal carcinoma so that in some cases even less aggressive
      treatment should be considered. Patients with these specific histological types
      should be informed of this relatively favourable prognosis. Secondly, management
      recommendations for special situations like Paget's disease (tumour of the
      nipple) and inflammatory breast carcinoma are presented.

PMID- 20824039
TI  - Primary Spindle Cell Sarcoma of the Breast.
AB  - BACKGROUND: Primary pure breast sarcoma is a rare disease and constitutes 0.2
      1.0% of all mammary malignancies. The establishment of a diagnosis of soft tissue
      sarcoma is difficult in adults. Immunohistochemical analysis usually proves to be
      helpful in indistinguishable cases. The simplistic step is to classify sarcomas
      on a simple descriptive basis as spindle cell sarcomas, myxoid sarcomas,
      pleomorphic sarcomas, and small round cell sarcomas. CASE REPORT: Here, we
      present a rare case of primary spindle cell sarcoma of the breast. A 43-year-old
      woman was admitted to our clinic with a 2-month history of a left breast lump.
      Histopathological examination showed a tumor of 2.5 cm in diameter and of nuclear
      and histological grade 2. In the immunohistochemical examination, vimentin
      positivity, high nuclear overexpression of P53, high Ki-67 and S-100, desmin,
      leukocyte common antigen, keratin, and smooth muscle antigen, CD34, HMB45 and EMA
      negativity were detected. CONCLUSION: Most invasive breast neoplasms are
      epithelial tumors, and mesenchymal breast tumors are rarely seen. In primary
      breast sarcoma, adequate surgical tumor excision, tumor grade, and tumor diameter
      seem to be the most important prognostic factors.

PMID- 20824040
TI  - Bilateral Mammary Tuberculosis Associated with a Borderline Ovarian Tumor.
AB  - BACKGROUND: Mammary tuberculosis is rare in the Western world. It has no defined
      clinical or imaging features, and has to be differentiated from breast cancer and
      an abscess. CASE REPORT: We present a case of mammary tuberculosis combined with
      borderline ovarian cancer. The bilateral breast tuberculosis was the first and
      only symptom of underlying tuberculosis with Ziehl-Neelsen-positive para-aortic
      lymph nodes. During further exploration, an asymptomatic pelvic mass was
      discovered, which appeared later to be a borderline ovarian tumor. The patient
      was treated with tuberculostatic therapy for 6 months, resulting in a complete
      regression of the breast lesions. She also underwent hysterectomy with bilateral
      salpingo-oophorectomy and lymph node dissection for her ovarian cancer.
      CONCLUSIONS: This case report emphasizes that breast tuberculosis should be
      included in the differential diagnosis of any atypical breast mass.

PMID- 20824041
TI  - Climacteric Complaints after Breast Cancer - Is HRT an Option?
AB  - Systemic estrogen depletion is the mechanism of action of most endocrine
      treatment strategies, and a common side effect of most chemotherapy regimens that
      are currently used to treat invasive breast cancer. The ensuing immediate and
      profound decline in estrogen levels is, however, often associated with
      considerable climacteric complaints. While oral estrogen add-back therapy is
      effective in alleviating menopausal symptoms, it is feared that it might also
      promote tumor cell growth. This concern is largely based on circumstantial
      evidence from large trials in healthy women, in which hormone replacement therapy
      (HRT) resulted in a slight, albeit significant, increase in incident breast
      cancer. In breast cancer survivors, however, evidence from studies remains
      controversial. Despite these caveats, the severity of symptoms and the lack of
      effective alternatives still cause many women to opt for HRT. Nevertheless, HRT
      cannot generally be recommended as first-line therapy for climacteric complaints
      in women with a history of breast cancer. It may, however, be a valid option for
      selected women with climacteric symptoms refractory to previous non-hormonal
      treatments. In these cases, an individualized risk-benefit analysis is imperative
      before treatment initiation, and a treatment duration of less than 5 years with
      intermittent withdrawal attempts should be aimed for.

PMID- 20824042
TI  - Marine plankton phenology and life history in a changing climate: current
      research and future directions.
AB  - Increasing availability and extent of biological ocean time series (from both in
      situ and satellite data) have helped reveal significant phenological variability
      of marine plankton. The extent to which the range of this variability is modified
      as a result of climate change is of obvious importance. Here we summarize recent
      research results on phenology of both phytoplankton and zooplankton. We suggest
      directions to better quantify and monitor future plankton phenology shifts,
      including (i) examining the main mode of expected future changes (ecological
      shifts in timing and spatial distribution to accommodate fixed environmental
      niches vs. evolutionary adaptation of timing controls to maintain fixed
      biogeography and seasonality), (ii) broader understanding of phenology at the
      species and community level (e.g. for zooplankton beyond Calanus and for
      phytoplankton beyond chlorophyll), (iii) improving and diversifying statistical
      metrics for indexing timing and trophic synchrony and (iv) improved consideration
      of spatio-temporal scales and the Lagrangian nature of plankton assemblages to
      separate time from space changes.

PMID- 20824043
TI  - Lipid sac area as a proxy for individual lipid content of arctic calanoid
      copepods.
AB  - We present an accurate, fast, simple and non-destructive photographic method to
      estimate wax ester and lipid content in single individuals of the calanoid
      copepod genus Calanus and test this method against gas-chromatographic lipid
      measurements.

PMID- 20824044
TI  - Epidermal growth factor receptor in glioma: signal transduction, neuropathology,
      imaging, and radioresistance.
AB  - Aberrant epidermal growth factor receptor (EGFR) signaling is common in cancer.
      Increased expression of wild type and mutant EGFR is a widespread feature of
      diverse types of cancer. EGFR signaling in cancer has been the focus of intense
      investigation for decades primarily for two reasons. First, aberrant EGFR
      signaling is likely to play an important role in the pathogenesis of cancer, and
      therefore, the mechanisms of EGFR-mediated oncogenic signaling are of interest.
      Second, the EGFR signaling system is an attractive target for therapeutic
      intervention. EGFR gene amplification and overexpression are a particularly
      striking feature of glioblastoma (GBM), observed in approximately 40% of tumors.
      GBM is the most common primary malignant tumor of the central nervous system in
      adults. In approximately 50% of tumors with EGFR amplification, a specific EGFR
      mutant (EGFRvIII, also known as EGFR type III, de2-7, Delta EGFR) can be
      detected. This mutant is highly oncogenic and is generated from a deletion of
      exons 2 to 7 of the EGFR gene, which results in an in-frame deletion of 267 amino
      acids from the extracellular domain of the receptor. EGFRvIII is unable to bind
      ligand, and it signals constitutively. Although EGFRvIII has the same signaling
      domain as the wild type receptor, it seems to generate a distinct set of
      downstream signals that may contribute to an increased tumorigenicity. In this
      review, we discuss recent progress in key aspects of EGFR signaling in GBM,
      focusing on neuropathology, signal transduction, imaging of the EGFR, and the
      role of the EGFR in mediating resistance to radiation therapy in GBM.

PMID- 20824045
TI  - Evolving role of bone biomarkers in castration-resistant prostate cancer.
AB  - The preferential metastasis of prostate cancer cells to bone disrupts the process
      of bone remodeling and results in lesions that cause significant pain and patient
      morbidity. Although prostate-specific antigen (PSA) is an established biomarker
      in prostate cancer, it provides only limited information relating to bone
      metastases and the treatment of metastatic bone disease with bisphosphonates or
      novel noncytotoxic targeted or biological agents that may provide clinical
      benefits without affecting PSA levels. As bone metastases develop, factors
      derived from bone metabolism are released into blood and urine, including N- and
      C-terminal peptide fragments of type 1 collagen and bone-specific alkaline
      phosphatase, which represent potentially useful biomarkers for monitoring
      metastatic bone disease. A number of clinical trials have investigated these bone
      biomarkers with respect to their diagnostic, prognostic, and predictive values.
      Results suggest that higher levels of bone biomarkers are associated with an
      increased risk of skeletal-related events and/or death. As a result of these
      findings, bone biomarkers are now being increasingly used as study end points,
      particularly in studies investigating novel agents with putative bone effects.
      Data from prospective clinical trials are needed to validate the use of bone
      biomarkers and to confirm that marker levels provide additional information
      beyond traditional methods of response evaluation for patients with metastatic
      prostate cancer.

PMID- 20824046
TI  - Assessment of acute antivascular effects of vandetanib with high-resolution
      dynamic contrast-enhanced computed tomographic imaging in a human colon tumor
      xenograft model in the nude rat.
AB  - Tumor size is not a reliable marker for the assessment of early antivascular
      effects of antiangiogenics. In the present study, we used 200-microm in-plane
      high-resolution dynamic contrast-enhanced computed tomography (DCE-CT) to
      noninvasively assess the immediate antivascular effects of vandetanib in a
      subcutaneous human colon cancer (LoVo) xenograft model in nude rats and to
      investigate correlation between changes in CT perfusion parameters and tumor
      volume or immunohistochemical end points. At 3 to 4 weeks after LoVo cell
      implantation, the animal was gavaged with either vandetanib (50 mg/kg) or vehicle
      twice (22 hours apart) and scanned with a preclinical DCE-CT scanner before (0
      hour) and after treatment (24 hours). Quantitative maps of blood flow (BF) and
      volume (BV) of the tumor were calculated from the acquired DCE-CT images. The
      rats were divided into nonhypovascular, hypovascular, and combined (regardless of
      vascularity) groups. In the nonhypovascular group, significant decreases in both
      tumor BF and BV were observed in the vandetanib-treated rats compared with
      increases in the vehicle-treated rats. A significant decrease in BV was detected
      in the vandetanib-treated rats in the combined group as well. No differences in
      tumor growth, vascular endothelial growth factor expression, microvessel density,
      or apoptosis were observed between vandetanib- and vehicle-treated rats in all
      three groups. These results demonstrate that BF and BV imaging biomarkers from
      DCE-CT imaging can be used for rapid monitoring of immediate (24 hours after)
      antimicrovascular effects of vandetanib on tumors, even in the absence of
      significant changes of tumor volume or clinically relevant immunohistochemical
      end points.

PMID- 20824047
TI  - Mutations in the c-Kit gene disrupt mitogen-activated protein kinase signaling
      during tumor development in adenoid cystic carcinoma of the salivary glands.
AB  - The Ras/mitogen-activated protein kinase (MAPK) pathway is considered to be a
      positive regulator of tumor initiation, progression, and maintenance. This study
      reports an opposite finding: we have found strong evidence that the MAPK pathway
      is inhibited in a subset of adenoid cystic carcinomas (ACCs) of the salivary
      glands. ACC tumors consistently overexpress the receptor tyrosine kinase (RTK) c
      Kit, which has been considered a therapeutic target. We performed mutational
      analysis of the c-Kit gene (KIT in 17 cases of ACC and found that 2 cases of ACC
      had distinct missense mutations in KIT at both the genomic DNA and messenger RNA
      levels. These mutations caused G664R and R796G amino acid substitutions in the
      kinase domains. Surprisingly, the mutations were functionally inactive in
      cultured cells. We observed a significant reduction of MAPK (ERK1/2) activity in
      tumor cells, as assessed by immunohistochemistry. We performed further mutational
      analysis of the downstream effectors in the c-Kit pathway in the genes HRAS,
      KRAS, NRAS, BRAF, PIK3CA, and PTEN. This analysis revealed that two ACC tumors
      without KIT mutations had missense mutations in either KRAS or BRAF, causing S17N
      K-Ras and V590I B-Raf mutants, respectively. Our functional analysis showed that
      proteins with these mutations were also inactive in cultured cells. This is the
      first time that MAPK activity from the RTK signaling has been shown to be
      inhibited by gene mutations during tumor development. Because ACC seems to
      proliferate despite inactivation of the c-Kit signaling pathway, we suggest that
      selective inhibition of c-Kit is probably not a suitable treatment strategy for
      ACC.

PMID- 20824048
TI  - Somatic expression of PyMT or activated ErbB2 induces estrogen-independent
      mammary tumorigenesis.
AB  - Estrogen signaling is required for the proliferation of normal breast epithelial
      cells. However, prophylactic inhibition of estrogen signaling fails to prevent
      56% of human breast cancer cases. The underlying mechanism is not well
      understood. Aberrant activation of growth factor signaling is known to provide
      alternative proliferation pathways in breast cells that are fully transformed,
      but it is not known whether activation of growth factor signaling can substitute
      for estrogen signaling in causing aberrant proliferation in the normal breast
      epithelium. Here, we report that in a retrovirus-based somatic mouse model
      (replication-competent ALV-LTR splice acceptor/tumor virus A) that closely mimics
      the evolution of sporadic human breast cancers, mammary epithelial cells
      harboring PyMT or activated ErbB2 evolve into tumors independent of estrogen or
      other ovarian functions in contrast to previous observations of estrogen
      dependent cancer formation in germ line mouse models of ErbB2 activation.
      Importantly, ErbB2 activation in normal mammary cells causes estrogen-independent
      proliferation in both estrogen receptor (ER)-negative cells as well as in
      normally quiescent ER-positive cells. Therefore, aberrant activation of growth
      factor signaling contributes to estrogen-independent proliferation of both
      preneoplastic and cancerous mammary cells, and prophylactic therapy against both
      growth factor signaling and estrogen signaling may need to be considered in women
      with increased risk of breast cancer.

PMID- 20824049
TI  - Long-term in vitro treatment of human glioblastoma cells with temozolomide
      increases resistance in vivo through up-regulation of GLUT transporter and aldo
      keto reductase enzyme AKR1C expression.
AB  - Glioblastoma (GBM) is the most frequent malignant glioma. Treatment of GBM
      patients is multimodal with maximum surgical resection, followed by concurrent
      radiation and chemotherapy with the alkylating drug temozolomide (TMZ). The
      present study aims to identify genes implicated in the acquired resistance of two
      human GBM cells of astrocytic origin, T98G and U373, to TMZ. Resistance to TMZ
      was induced by culturing these cells in vitro for months with incremental TMZ
      concentrations up to 1 mM. Only partial resistance to TMZ has been achieved and
      was demonstrated in vivo in immunocompromised mice bearing orthotopic U373 and
      T98G xenografts. Our data show that long-term treatment of human astroglioma
      cells with TMZ induces increased expression of facilitative glucose
      transporter/solute carrier GLUT/SLC2A family members, mainly GLUT-3, and of the
      AKR1C family of proteins. The latter proteins are phase 1 drug-metabolizing
      enzymes involved in the maintenance of steroid homeostasis, prostaglandin
      metabolism, and metabolic activation of polycyclic aromatic hydrocarbons. GLUT-3
      has been previously suggested to exert roles in GBM neovascularization processes,
      and TMZ was found to exert antiangiogenic effects in experimental gliomas. AKR1C1
      was previously shown to be associated with oncogenic potential, with
      proproliferative effects similar to AKR1C3 in the latter case. Both AKR1C1 and
      AKR1C2 proteins are involved in cancer pro-proliferative cell chemoresistance.
      Selective targeting of GLUT-3 in GBM and/or AKR1C proteins (by means of
      jasmonates, for example) could thus delay the acquisition of resistance to TMZ of
      astroglioma cells in the context of prolonged treatment with this drug.

PMID- 20824050
TI  - Interdependence of gemcitabine treatment, transporter expression, and resistance
      in human pancreatic carcinoma cells.
AB  - Gemcitabine is widely used as first-line chemotherapeutic drug in the treatment
      of pancreatic cancer. Our previous experimental chemotherapy studies have shown
      that treatment of human pancreatic carcinoma cells with 5-fluorouracil (5-FU)
      alters the cellular transporter expression profile and that modulation of the
      expression of multidrug resistance protein 5 (MRP5; ABCC5) influences the
      chemoresistance of these tumor cells. Here, we studied the influence of acute and
      chronic gemcitabine treatment on the expression of relevant uptake and export
      transporters in pancreatic carcinoma cells by reverse transcription-polymerase
      chain reaction (RT-PCR), quantitative RT-PCR, and immunoblot analyses. The
      specific role of MRP5 in cellular gemcitabine sensitivity was studied by
      cytotoxicity assays using MRP5-overexpressing and MRP5-silenced cells. Exposure
      to gemcitabine (12 nM for 3 days) did not alter the messenger RNA (mRNA)
      expression of MRP1, MRP3, MRP5, and equilibrative nucleoside transporter 1
      (ENT1), whereas high dosages of the drug (20 microM for 1 hour) elicited up
      regulation of these transporters in most cell lines studied. In cells with
      acquired gemcitabine resistance (up to 160 nM gemcitabine), the mRNA or protein
      expression of the gemcitabine transporters MRP5 and ENT1 was upregulated in
      several cell lines. Combined treatment with 5-FU and gemcitabine caused a 5- to
      40-fold increase in MRP5 and ENT1 expressions. Cytotoxicity assays using either
      MRP5-overexpressing (HEK and PANC-1) or MRP5-silenced (PANC1/shMRP5) cells
      indicated that MRP5 contributes to gemcitabine resistance. Thus, our novel data
      not only on drug-induced alterations of transporter expression relevant for
      gemcitabine uptake and export but also on the link between gemcitabine
      sensitivity and MRP5 expression may lead to improved strategies of future
      chemotherapy regimens using gemcitabine in pancreatic carcinoma patients.

PMID- 20824051
TI  - Reactive astrocytes protect melanoma cells from chemotherapy by sequestering
      intracellular calcium through gap junction communication channels.
AB  - Brain metastases are highly resistant to chemotherapy. Metastatic tumor cells are
      known to exploit the host microenvironment for their growth and survival. We
      report here that melanoma brain metastases are surrounded and infiltrated by
      activated astrocytes, and we hypothesized that these astrocytes can play a role
      similar to their established ability to protect neurons from apoptosis. In
      coculture experiments, astrocytes, but not fibroblasts, reduced apoptosis in
      human melanoma cells treated with various chemotherapeutic drugs. This
      chemoprotective effect was dependent on physical contact and gap junctional
      communication between astrocytes and tumor cells. Moreover, the protective effect
      of astrocytes resulted from their sequestering calcium from the cytoplasm of
      tumor cells. These data suggest that brain tumors can, in principle, harness the
      neuroprotective effects of reactive astrocytes for their own survival and
      implicate a heretofore unrecognized mechanism for resistance in brain metastasis
      that might be of relevance in the clinic.

PMID- 20824053
TI  - High amplitude phase resetting in rev-erbalpha/per1 double mutant mice.
AB  - Over time, organisms developed various strategies to adapt to their environment.
      Circadian clocks are thought to have evolved to adjust to the predictable rhythms
      of the light-dark cycle caused by the rotation of the Earth around its own axis.
      The rhythms these clocks generate persist even in the absence of environmental
      cues with a period of about 24 hours. To tick in time, they continuously
      synchronize themselves to the prevailing photoperiod by appropriate phase shifts.
      In this study, we disrupted two molecular components of the mammalian circadian
      oscillator, Rev-Erbalpha and Period1 (Per1). We found that mice lacking these
      genes displayed robust circadian rhythms with significantly shorter periods under
      constant darkness conditions. Strikingly, they showed high amplitude resetting in
      response to a brief light pulse at the end of their subjective night phase, which
      is rare in mammals. Surprisingly, Cry1, a clock component not inducible by light
      in mammals, became slightly inducible in these mice. Taken together, Rev-Erbalpha
      and Per1 may be part of a mechanism preventing drastic phase shifts in mammals.

PMID- 20824052
TI  - Labeling of oxidizable proteins with a photoactivatable analog of the antitumor
      agent DMXAA: evidence for redox signaling in its mode of action.
AB  - The signaling pathway(s) and molecular target(s) for 5,6-dimethylxanthenone-4
      acetic acid (DMXAA), a tumor vascular disrupting agent in late stages of clinical
      development, are still undefined. As an approach toward identifying potential
      targets for DMXAA, a tritiated azido-analog of DMXAA was used to probe for
      cellular binding proteins. More than 20 cytosolic proteins from murine
      splenocytes, RAW 264.7 cells, and the HECPP immortalized endothelial cells were
      photoaffinity-labeled. Although no protein domain, fold, or binding site for a
      specific ligand was found to be shared by all the candidate proteins, essentially
      all were noted to be oxidizable proteins, implicating a role for redox signaling
      in the action of DMXAA. Consistent with this hypothesis, DMXAA caused an increase
      in concentrations of reactive oxygen species (ROS) in RAW264.7 cells during the
      first 2 hours. This increase in ROS was suppressed in the presence of the
      antioxidant, N-acetyl-L-cysteine, which also suppressed DMXAA-induced cytokine
      production in the RAW 264.7 cells with no effects on cell viability. Short
      interfering RNA (siRNA)-mediated knockdown of one of the photoaffinity-labeled
      proteins, superoxide dismutase 1, an ROS scavenger, resulted in an increase in
      tumor necrosis factor-alpha production by RAW 264.7 cells in response to DMXAA
      compared with negative or positive controls transfected with nontargeting or
      lamin A/C-targeting siRNA molecules, respectively. The results from these lines
      of study all suggest that redox signaling plays a central role in cytokine
      induction by DMXAA.

PMID- 20824054
TI  - Meaning of missing values in eyewitness recall and accident records.
AB  - BACKGROUND: Eyewitness recalls and accident records frequently do not mention the
      conditions and behaviors of interest to researchers and lead to missing values
      and to uncertainty about the prevalence of these conditions and behaviors
      surrounding accidents. Missing values may occur because eyewitnesses report the
      presence but not the absence of obvious clues/accident features. We examined this
      possibility. METHODOLOGY/PRINCIPAL FINDINGS: Participants watched car accident
      videos and were asked to recall as much information as they could remember about
      each accident. The results showed that eyewitnesses were far more likely to
      report the presence of present obvious clues than the absence of absent obvious
      clues even though they were aware of their absence. CONCLUSIONS: One of the
      principal mechanisms causing missing values may be eyewitnesses' tendency to not
      report the absence of obvious features. We discuss the implications of our
      findings for both retrospective and prospective analyses of accident records, and
      illustrate the consequences of adopting inappropriate assumptions about the
      meaning of missing values using the Avaluator Avalanche Accident Prevention Card.

PMID- 20824055
TI  - Topoisomerase II-mediated DNA damage is differently repaired during the cell
      cycle by non-homologous end joining and homologous recombination.
AB  - Topoisomerase II (Top2) is a nuclear enzyme involved in several metabolic
      processes of DNA. Chemotherapy agents that poison Top2 are known to induce
      persistent protein-mediated DNA double strand breaks (DSB). In this report, by
      using knock down experiments, we demonstrated that Top2alpha was largely
      responsible for the induction of gammaH2AX and cytotoxicity by the Top2 poisons
      idarubicin and etoposide in normal human cells. As DSB resulting from Top2
      poisons-mediated damage may be repaired by non-homologous end joining (NHEJ) or
      homologous recombination (HR), we aimed to analyze both DNA repair pathways. We
      found that DNA-PKcs was rapidly activated in human cells, as evidenced by
      autophosphorylation at serine 2056, following Top2-mediated DNA damage. The
      chemical inhibition of DNA-PKcs by wortmannin and vanillin resulted in an
      increased accumulation of DNA DSB, as evaluated by the comet assay. This was
      supported by a hypersensitive phenotype to Top2 poisons of Ku80- and DNA-PKcs-
      defective Chinese hamster cell lines. We also showed that Rad51 protein levels,
      Rad51 foci formation and sister chromatid exchanges were increased in human cells
      following Top2-mediated DNA damage. In support, BRCA2- and Rad51C- defective
      Chinese hamster cells displayed hypersensitivity to Top2 poisons. The analysis by
      immunofluorescence of the DNA DSB repair response in synchronized human cell
      cultures revealed activation of DNA-PKcs throughout the cell cycle and Rad51 foci
      formation in S and late S/G2 cells. Additionally, we found an increase of DNA
      PKcs-mediated residual repair events, but not Rad51 residual foci, into
      micronucleated and apoptotic cells. Therefore, we conclude that in human cells
      both NHEJ and HR are required, with cell cycle stage specificity, for the repair
      of Top2-mediated reversible DNA damage. Moreover, NHEJ-mediated residual repair
      events are more frequently associated to irreversibly damaged cells.

PMID- 20824056
TI  - Antibody targeting of cathepsin S inhibits angiogenesis and synergistically
      enhances anti-VEGF.
AB  - BACKGROUND: Angiogenesis is a key hallmark of tumourigenesis and its inhibition
      is a proven strategy for the development of novel anti-cancer therapeutics. An
      important aspect of early angiogenesis is the co-ordinated migration and invasion
      of endothelial cells through the hypoxic tumour tissue. Cathepsin S has been
      shown to play an important role in angiogenesis as has vascular endothelial
      growth factor (VEGF). We sought to assess the anti-angiogenic effect of Fsn0503,
      a novel cathepsin S inhibitory antibody, when combined with anti-VEGF on vascular
      development. METHODOLOGY/PRINCIPAL FINDINGS: Cathepsin S expression and secretion
      from endothelial cells was characterised using RT-PCR and western blotting. We
      further show that cathepsin S promotes pericellular hydrolysis of extracellular
      matrix components in the tumour microenvironment and facilitates endothelial
      invasion. The cathepsin S inhibitory antibody, Fsn0503, blocks extracellular
      proteolysis, inhibiting endothelial invasion and tube formation in cell-based
      assays. The anti-angiogenic effects of Fsn0503 were also shown in vivo where it
      significantly retarded the development of vasculature in human xenograft models.
      Furthermore, when Fsn0503 was combined with an anti-VEGF antibody, a synergistic
      inhibition of microvascular development was observed. CONCLUSIONS/SIGNIFICANCE:
      Taken together, this data demonstrates that the antibody-mediated targeting of
      cathepsin S represents a novel method of inhibiting angiogenesis. Furthermore,
      when used in combination with anti-VEGF therapies, Fsn0503 has the potential to
      significantly enhance current treatments of tumour neovascularisation and may
      also be of use in the treatment of other conditions associated with inappropriate
      angiogenesis.

PMID- 20824057
TI  - A pipeline to determine RT-QPCR control genes for evolutionary studies:
      application to primate gene expression across multiple tissues.
AB  - Because many species-specific phenotypic differences are assumed to be caused by
      differential regulation of gene expression, many recent investigations have
      focused on measuring transcript abundance. Despite the availability of high
      throughput platforms, quantitative real-time polymerase chain reaction (RT-QPCR)
      is often the method of choice because of its low cost and wider dynamic range.
      However, the accuracy of this technique heavily relies on the use of multiple
      valid control genes for normalization. We created a pipeline for choosing genes
      potentially useful as RT-QPCR control genes for measuring expression between
      human and chimpanzee samples across multiple tissues, using published microarrays
      and a measure of tissue-specificity. We identified 13 genes from the pipeline and
      from commonly used control genes: ACTB, USP49, ARGHGEF2, GSK3A, TBP, SDHA,
      EIF2B2, GPDH, YWHAZ, HPTR1, RPL13A, HMBS, and EEF2. We then tested these
      candidate genes and validated their expression stability across species. We
      established the rank order of the most preferable set of genes for single and
      combined tissues. Our results suggest that for at least three tissues (cerebral
      cortex, liver, and skeletal muscle), EIF2B2, EEF2, HMBS, and SDHA are useful
      genes for normalizing human and chimpanzee expression using RT-QPCR.
      Interestingly, other commonly used control genes, including TBP, GAPDH, and,
      especially ACTB do not perform as well. This pipeline could be easily adapted to
      other species for which expression data exist, providing taxonomically
      appropriate control genes for comparisons of gene expression among species.

PMID- 20824058
TI  - Rapid changes in the light/dark cycle disrupt memory of conditioned fear in mice.
AB  - BACKGROUND: Circadian rhythms govern many aspects of physiology and behavior
      including cognitive processes. Components of neural circuits involved in learning
      and memory, e.g., the amygdala and the hippocampus, exhibit circadian rhythms in
      gene expression and signaling pathways. The functional significance of these
      rhythms is still not understood. In the present study, we sought to determine the
      impact of transiently disrupting the circadian system by shifting the light/dark
      (LD) cycle. Such "jet lag" treatments alter daily rhythms of gene expression that
      underlie circadian oscillations as well as disrupt the synchrony between the
      multiple oscillators found within the body. METHODOLOGY/PRINCIPAL FINDINGS: We
      subjected adult male C57Bl/6 mice to a contextual fear conditioning protocol
      either before or after acute phase shifts of the LD cycle. As part of this study,
      we examined the impact of phase advances and phase delays, and the effects of
      different magnitudes of phase shifts. Under all conditions tested, we found that
      recall of fear conditioned behavior was specifically affected by the jet lag. We
      found that phase shifts potentiated the stress-evoked corticosterone response
      without altering baseline levels of this hormone. The jet lag treatment did not
      result in overall sleep deprivation, but altered the temporal distribution of
      sleep. Finally, we found that prior experience of jet lag helps to compensate for
      the reduced recall due to acute phase shifts. CONCLUSIONS/SIGNIFICANCE: Acute
      changes to the LD cycle affect the recall of fear-conditioned behavior. This
      suggests that a synchronized circadian system may be broadly important for normal
      cognition and that the consolidation of memories may be particularly sensitive to
      disruptions of circadian timing.

PMID- 20824059
TI  - The peptide sequence of diacyl lipopeptides determines dendritic cell TLR2
      mediated NK activation.
AB  - Natural killer (NK) cells are lymphocyte effectors that are activated to control
      certain microbial infections and tumors. Many NK-activating and regulating
      receptors are involved in regulating NK cell function. In addition, activation of
      naive NK cells is fundamentally triggered by cytokines or myeloid dendritic cells
      (mDC) in various modes. In this study, we synthesized 16 S-[2,3
      bis(palmitoyl)propyl]cysteine (Pam2Cys) lipopeptides with sequences designed from
      lipoproteins of Staphylococcus aureus, and assessed their functional properties
      using mouse (C57BL/6) bone marrow-derived DC (BMDC) and NK cells. NK cell
      activation was evaluated by three criteria: IFN-gamma production, up-regulation
      of NK activation markers and cytokines, and NK target (B16D8 cell) cytotoxicity.
      The diacylated lipopeptides acted as TLR2 ligands, inducing up-regulation of
      CD25/CD69/CD86, IL-6, and IL-12p40, which represent maturation of BMDC.
      Strikingly, the Pam2Cys lipopeptides induced mouse NK cell activation based on
      these criteria. Cell-cell contact by Pam2Cys peptide-stimulated BMDC and NK cells
      rather than soluble mediators released by stimulated BMDC induced activation of
      NK cells. For most lipopeptides, the BMDC TLR2/MyD88 pathway was responsible for
      driving NK activation, while some slightly induced direct activation of NK cells
      via the TLR2/MyD88 pathway in NK cells. The potential for NK activation was
      critically regulated by the peptide primary sequence. Hydrophobic or proline
      containing sequences proximal to the N-terminal lipid moiety interfered with the
      ability of lipopeptides to induce BMDC-mediated NK activation. This mode of NK
      activation is distinctly different from that induced by polyI:C, which is closely
      associated with type I IFN-inducing pathways of BMDC. These results imply that
      the MyD88 pathway of BMDC governs an alternative NK-activating pathway in which
      the peptide sequence of TLR2-agonistic lipopeptides critically affects the
      potential for NK activation.

PMID- 20824060
TI  - DNA clasping by mycobacterial HU: the C-terminal region of HupB mediates
      increased specificity of DNA binding.
AB  - BACKGROUND: HU a small, basic, histone like protein is a major component of the
      bacterial nucleoid. E. coli has two subunits of HU coded by hupA and hupB genes
      whereas Mycobacterium tuberculosis (Mtb) has only one subunit of HU coded by ORF
      Rv2986c (hupB gene). One noticeable feature regarding Mtb HupB, based on sequence
      alignment of HU orthologs from different bacteria, was that HupB(Mtb) bears at
      its C-terminal end, a highly basic extension and this prompted an examination of
      its role in Mtb HupB function. METHODOLOGY/PRINCIPAL FINDINGS: With this
      objective two clones of Mtb HupB were generated; one expressing full length HupB
      protein (HupB(Mtb)) and another which expresses only the N terminal region (first
      95 amino acid) of hupB (HupB(MtbN)). Gel retardation assays revealed that
      HupB(MtbN) is almost like E. coli HU (heat stable nucleoid protein) in terms of
      its DNA binding, with a binding constant (K(d)) for linear dsDNA greater than
      1000 nM, a value comparable to that obtained for the HUalphaalpha and HUalphabeta
      forms. However CTR (C-terminal Region) of HupB(Mtb) imparts greater specificity
      in DNA binding. HupB(Mtb) protein binds more strongly to supercoiled plasmid DNA
      than to linear DNA, also this binding is very stable as it provides DNase I
      protection even up to 5 minutes. Similar results were obtained when the abilities
      of both proteins to mediate protection against DNA strand cleavage by hydroxyl
      radicals generated by the Fenton's reaction, were compared. It was also observed
      that both the proteins have DNA binding preference for A:T rich DNA which may
      occur at the regulatory regions of ORFs and the oriC region of Mtb.
      CONCLUSIONS/SIGNIFICANCE: These data thus point that HupB(Mtb) may participate in
      chromosome organization in-vivo, it may also play a passive, possibly an
      architectural role.

PMID- 20824061
TI  - Structural and mutational analysis of functional differentiation between
      synaptotagmins-1 and -7.
AB  - Synaptotagmins are known to mediate diverse forms of Ca2+-triggered exocytosis
      through their C2 domains, but the principles underlying functional
      differentiation among them are unclear. Synaptotagmin-1 functions as a Ca2+
      sensor in neurotransmitter release at central nervous system synapses, but
      synaptotagmin-7 does not, and yet both isoforms act as Ca2+ sensors in chromaffin
      cells. To shed light into this apparent paradox, we have performed rescue
      experiments in neurons from synaptotagmin-1 knockout mice using a chimera that
      contains the synaptotagmin-1 sequence with its C2B domain replaced by the
      synaptotagmin-7 C2B domain (Syt1/7). Rescue was not achieved either with the WT
      Syt1/7 chimera or with nine mutants where residues that are distinct in
      synaptotagmin-7 were restored to those present in synaptotagmin-1. To investigate
      whether these results arise because of unique conformational features of the
      synaptotagmin-7 C2B domain, we determined its crystal structure at 1.44 A
      resolution. The synaptotagmin-7 C2B domain structure is very similar to that of
      the synaptotagmin-1 C2B domain and contains three Ca2+-binding sites. Two of the
      Ca2+-binding sites of the synaptotagmin-7 C2B domain are also present in the
      synaptotagmin-1 C2B domain and have analogous ligands to those determined for the
      latter by NMR spectroscopy, suggesting that a discrepancy observed in a crystal
      structure of the synaptotagmin-1 C2B domain arose from crystal contacts. Overall,
      our results suggest that functional differentiation in synaptotagmins arises in
      part from subtle sequence changes that yield dramatic functional differences.

PMID- 20824062
TI  - The potential for enhancing the power of genetic association studies in African
      Americans through the reuse of existing genotype data.
AB  - We consider the feasibility of reusing existing control data obtained in genetic
      association studies in order to reduce costs for new studies. We discuss
      controlling for the population differences between cases and controls that are
      implicit in studies utilizing external control data. We give theoretical
      calculations of the statistical power of a test due to Bourgain et al (Am J Human
      Genet 2003), applied to the problem of dealing with case-control differences in
      genetic ancestry related to population isolation or population admixture.
      Theoretical results show that there may exist bounds for the non-centrality
      parameter for a test of association that places limits on study power even if
      sample sizes can grow arbitrarily large. We apply this method to data from a
      multi-center, geographically-diverse, genome-wide association study of breast
      cancer in African-American women. Our analysis of these data shows that admixture
      proportions differ by center with the average fraction of European admixture
      ranging from approximately 20% for participants from study sites in the Eastern
      United States to 25% for participants from West Coast sites. However, these
      differences in average admixture fraction between sites are largely
      counterbalanced by considerable diversity in individual admixture proportion
      within each study site. Our results suggest that statistical correction for
      admixture differences is feasible for future studies of African-Americans,
      utilizing the existing controls from the African-American Breast Cancer study,
      even if case ascertainment for the future studies is not balanced over the same
      centers or regions that supplied the controls for the current study.

PMID- 20824063
TI  - Transcriptional and post-transcriptional regulation of proangiogenic factors by
      the unfolded protein response.
AB  - BACKGROUND: Inadequate extracellular conditions can adversely affect the
      environment of the ER and impinge on the maturation of nascent proteins. The
      resultant accumulation of unfolded proteins activates a signal transduction
      pathway, known as the unfolded protein response, which serves primarily to
      protect the cell during stress and helps restore homeostasis to the ER. PRINCIPAL
      FINDINGS: Microarray analysis of the unfolded protein response in a human
      medulloblastoma cell line treated with thapsigargin revealed that, in addition to
      known targets, a large number of proangiogenic factors were up-regulated. Real
      Time PCR analyses confirmed that four of these factors, VEGFA, FGF2, angiogenin
      and IL8, were transcriptionally up-regulated in multiple cell lines by various ER
      stress inducers. Our studies on VEGFA regulation revealed that XBP-1(S), a UPR
      inducible transcription factor, bound to two regions on the VEGFA promoter, and
      analysis of XBP-1 null mouse embryonic fibroblasts revealed that it contributes
      to VEGFA expression in response to ER stress. ATF4, another UPR-inducible
      transcription factor, also binds to the VEGFA gene, although its contribution to
      VEGFA transcription appeared to be fairly modest. We also found that VEGFA mRNA
      stability is increased in response to UPR activation, via activation of AMP
      kinase, demonstrating that increased mRNA levels occur at two regulatory points.
      In keeping with the mRNA levels, we found that VEGFA protein is secreted at
      levels as high as or higher than that achieved in response to hypoxia.
      CONCLUSIONS AND SIGNIFICANCE: Our results indicate that the UPR plays a
      significant role in inducing positive regulators of angiogenesis. It also
      regulates VEGFA expression at transcriptional, post-transcriptional and post
      translational levels and is likely to have widespread implications for promoting
      angiogenesis in response to normal physiological cues as well as in pathological
      conditions like cancer.

PMID- 20824064
TI  - Identifying regulators for EAG1 channels with a novel electrophysiology and
      tryptophan fluorescence based screen.
AB  - BACKGROUND: Ether-a-go-go (EAG) channels are expressed throughout the central
      nervous system and are also crucial regulators of cell cycle and tumor
      progression. The large intracellular amino- and carboxy- terminal domains of EAG1
      each share similarity with known ligand binding motifs in other proteins, yet
      EAG1 channels have no known regulatory ligands. METHODOLOGY/PRINCIPAL FINDINGS:
      Here we screened a library of small biologically relevant molecules against EAG1
      channels with a novel two-pronged screen to identify channel regulators. In one
      arm of the screen we used electrophysiology to assess the functional effects of
      the library compounds on full-length EAG1 channels. In an orthogonal arm, we used
      tryptophan fluorescence to screen for binding of the library compounds to the
      isolated C-terminal region. CONCLUSIONS/SIGNIFICANCE: Several compounds from the
      flavonoid, indole and benzofuran chemical families emerged as binding partners
      and/or regulators of EAG1 channels. The two-prong screen can aid ligand and drug
      discovery for ligand-binding domains of other ion channels.

PMID- 20824065
TI  - Induction of erythroid differentiation in human erythroleukemia cells by
      depletion of malic enzyme 2.
AB  - Malic enzyme 2 (ME2) is a mitochondrial enzyme that catalyzes the conversion of
      malate to pyruvate and CO2 and uses NAD as a cofactor. Higher expression of this
      enzyme correlates with the degree of cell de-differentiation. We found that ME2
      is expressed in K562 erythroleukemia cells, in which a number of agents have been
      found to induce differentiation either along the erythroid or the myeloid
      lineage. We found that knockdown of ME2 led to diminished proliferation of tumor
      cells and increased apoptosis in vitro. These findings were accompanied by
      differentiation of K562 cells along the erythroid lineage, as confirmed by
      staining for glycophorin A and hemoglobin production. ME2 knockdown also totally
      abolished growth of K562 cells in nude mice. Increased ROS levels, likely
      reflecting increased mitochondrial production, and a decreased NADPH/NADP+ ratio
      were noted but use of a free radical scavenger to decrease inhibition of ROS
      levels did not reverse the differentiation or apoptotic phenotype, suggesting
      that ROS production is not causally involved in the resultant phenotype. As might
      be expected, depletion of ME2 induced an increase in the NAD+/NADH ratio and ATP
      levels fell significantly. Inhibition of the malate-aspartate shuttle was
      insufficient to induce K562 differentiation. We also examined several
      intracellular signaling pathways and expression of transcription factors and
      intermediate filament proteins whose expression is known to be modulated during
      erythroid differentiation in K562 cells. We found that silencing of ME2 leads to
      phospho-ERK1/2 inhibition, phospho-AKT activation, increased GATA-1 expression
      and diminished vimentin expression. Metabolomic analysis, conducted to gain
      insight into intermediary metabolic pathways that ME2 knockdown might affect,
      showed that ME2 depletion resulted in high orotate levels, suggesting potential
      impairment of pyrimidine metabolism. Collectively our data point to ME2 as a
      potentially novel metabolic target for leukemia therapy.

PMID- 20824067
TI  - Microliter-bioreactor array with buoyancy-driven stirring for human hematopoietic
      stem cell culture.
AB  - This work presents the development of an array of bioreactors where finely
      controlled stirring is provided at the microliter scale (100-300 mul). The
      microliter-bioreactor array is useful for performing protocol optimization in up
      to 96 parallel experiments of hematopoietic stem cell (HSC) cultures. Exploring a
      wide range of experimental conditions at the microliter scale minimizes cost and
      labor. Once the cell culture protocol is optimized, it can be applied to large
      scale bioreactors for stem cell production at the clinical level. The controlled
      stirring inside the wells of a standard 96-well plate is provided by buoyancy
      driven thermoconvection. The temperature and velocity fields within the culture
      volume are determined with numerical simulations. The numerical results are
      verified with experimental velocity measurements using microparticle image
      velocimetry (muPIV) and are used to define feasible experimental conditions for
      stem cell cultures. To test the bioreactor array's functionality, human umbilical
      cord blood-derived CD34(+) cells were cultured for 7 days at five different
      stirring conditions (0.24-0.58 mums) in six repeated experiments. Cells were
      characterized in terms of proliferation, and flow cytometry measurements of
      viability and CD34 expression. The microliter-bioreactor array demonstrates its
      ability to support HSC cultures under stirred conditions without adversely
      affecting the cell behavior. Because of the highly controlled operative
      conditions, it can be used to explore culture conditions where the mass transport
      of endogenous and exogenous growth factors is selectively enhanced, and cell
      suspension provided. While the bioreactor array was developed for culturing HSCs,
      its application can be extended to other cell types.

PMID- 20824066
TI  - PolyADP-ribosylation is required for pronuclear fusion during postfertilization
      in mice.
AB  - BACKGROUND: During fertilization, pronuclear envelope breakdown (PNEB) is
      followed by the mingling of male and female genomes. Dynamic chromatin and
      protein rearrangements require posttranslational modification (PTM) for the
      postfertilization development. METHODOLOGY/PRINCIPAL FINDINGS: Inhibition of
      poly(ADP-ribose) polymerase activity (PARylation) by either PJ-34 or 5-AIQ
      resulted in developmental arrest of fertilized embryos at the PNEB. PARylation
      inhibition affects spindle bundle formation and phosphorylation of Erk molecules
      of metaphase II (MII) unfertilized oocytes. We found a frequent appearance of
      multiple pronuclei (PN) in the PARylation-inhibited embryos, suggesting defective
      polymerization of tubulins. Attenuated phosphorylation of lamin A/C by PARylation
      was detected in the PARylation-inhibited embryos at PNEB. This was associated
      with sustained localization of heterodomain protein 1 (HP1) at the PN of the one
      cell embryos arrested by PARylation inhibition. CONCLUSIONS/SIGNIFICANCE: Our
      findings indicate that PARylation is required for pronuclear fusion during
      postfertilization processes. These data further suggest that PARylation regulates
      protein dynamics essential for the beginning of mouse zygotic development.
      PARylation and its involving signal-pathways may represent potential targets as
      contraceptives.

PMID- 20824068
TI  - Numerical study of in situ preconcentration for rapid and sensitive nanoparticle
      detection.
AB  - This paper presents a numerical study of a preconcentrator design that can
      effectively increase the binding rate at the sensor in a real time manner. The
      particle enrichment is realized by the ac electrothermal (ACET) effect, which
      induces fluid movement to carry nanoparticles toward the sensor. The ACET is the
      only electrical method to manipulate a biological sample of medium to high ionic
      strength (>0.1 Sm, e.g., 0.06x phosphate buffered saline). The preconcentrator
      consists of a pair of electrodes striding over the sensor, simple to implement as
      it is electrically controlled. This preconcentrator design is compatible and can
      be readily integrated with many types of micro- to nanosensors. By applying an ac
      signal over the electrodes, local vortices will generate a large velocity
      perpendicular to the reaction surface, which enhances transport of analytes
      toward the sensor. Our simulation shows that the binding rate at the sensor
      surface is greatly enhanced. Our study also shows that the collection of analytes
      will be affected by various parameters such as channel height, inlet velocity,
      and sensor size, and our results will provide guidance in optimization of the
      preconcentrator design.

PMID- 20824069
TI  - Tunable acoustophoretic band-pass particle sorter.
AB  - Acoustophoretic separation in microchannels offers a promising avenue for high
      throughput, label-free, cell and particle separation for many applications.
      However, previous acoustophoretic separation approaches have been limited to a
      single size separation threshold, analogous to a binary filter, (i.e., high-pass
      or low-pass). Here, we describe a tunable acoustophoretic separation architecture
      capable of sorting cells and particles based on a range of sizes, analogous to a
      band-pass filter. The device is capable of sorting an arbitrary range of particle
      sizes between 3 and 10 mum in diameter with high efficiency (transfer
      fraction=0.98+/-0.02) at a throughput of approximately 10(8)
      particleshmicrochannel.

PMID- 20824070
TI  - Early experience in the treatment of intra-cranial aneurysms by endovascular flow
      diversion: a multicentre prospective study.
AB  - INTRODUCTION: Flow diversion is a new approach to the endovascular treatment of
      intracranial aneurysms which uses a high density mesh stent to induce sac
      thrombosis. These devices have been designed for the treatment of complex shaped
      and large size aneurysms. So far published safety and efficacy data on this
      approach is sparse. MATERIAL AND METHODS: Over 8 months, standardized clinical
      and angiographic data were collected on 70 patients treated with a flow diverter
      device (SILK flow diverter (SFD)) in 18 centres worldwide. Treatment and early
      follow up details were audited centrally. SFDs were deployed alone in 57 (81%) or
      with endosaccular coils in 10 (14%) aneurysms, which included: 44 (63%) saccular,
      26 (37%) fusiform shapes and 18 (26%) small, 37 (53%) large, 15 (21%) giant
      sizes. Treatment outcome data up to 30 days were reported for all patients, with
      clinical (50 patients) and imaging (49 patients) follow up (median 119 days) data
      available. RESULTS: Difficulties in SFD deployment were reported in 15 (21%) and
      parent artery thrombosis in 8 (11%) procedures. Procedural complications caused
      stroke in 1 and serious extracranial bleeding in 3 patients; 2 of whom developed
      fatal pneumonias. Delayed worsening of symptoms occurred in 5 patients (3
      transient, 1 permanent neurological deficit, and 1 death) and fatal aneurysm
      bleeding in 1 patient. Overall permanent morbidity rates were 2 (4%) and
      mortality 4 (8%). Statistical analysis revealed no significant association
      between complications and variables related to treated aneurysm morphology or
      rupture status. CONCLUSION: This series is the largest reporting outcome of the
      new treatment approach and provides data for future study design. Procedural
      difficulties in SFD deployment were frequent and anti-thrombosis prophylaxis
      appears to reduce the resulting clinical sequelae, but at the cost of morbidity
      due to extracranial bleeding. Delayed morbidity appears to be a consequence of
      the new approach and warrants care in selecting patients for treatment and future
      larger studies.

PMID- 20824071
TI  - Response to mechanical stress is mediated by the TRPA channel painless in the
      Drosophila heart.
AB  - Mechanotransduction modulates cellular functions as diverse as migration,
      proliferation, differentiation, and apoptosis. It is crucial for organ
      development and homeostasis and leads to pathologies when defective. However,
      despite considerable efforts made in the past, the molecular basis of
      mechanotransduction remains poorly understood. Here, we have investigated the
      genetic basis of mechanotransduction in Drosophila. We show that the fly heart
      senses and responds to mechanical forces by regulating cardiac activity. In
      particular, pauses in heart activity are observed under acute mechanical
      constraints in vivo. We further confirm by a variety of in situ tests that these
      cardiac arrests constitute the biological force-induced response. In order to
      identify molecular components of the mechanotransduction pathway, we carried out
      a genetic screen based on the dependence of cardiac activity upon mechanical
      constraints and identified Painless, a TRPA channel. We observe a clear absence
      of in vivo cardiac arrest following inactivation of painless and further
      demonstrate that painless is autonomously required in the heart to mediate the
      response to mechanical stress. Furthermore, direct activation of Painless is
      sufficient to produce pauses in heartbeat, mimicking the pressure-induced
      response. Painless thus constitutes part of a mechanosensitive pathway that
      adjusts cardiac muscle activity to mechanical constraints. This constitutes the
      first in vivo demonstration that a TRPA channel can mediate cardiac
      mechanotransduction. Furthermore, by establishing a high-throughput system to
      identify the molecular players involved in mechanotransduction in the
      cardiovascular system, our study paves the way for understanding the mechanisms
      underlying a mechanotransduction pathway.

PMID- 20824072
TI  - A negative regulatory loop between microRNA and Hox gene controls posterior
      identities in Caenorhabditis elegans.
AB  - MicroRNAs (miRNAs) have been found to regulate gene expression across eukaryotic
      species, but the function of most miRNA genes remains unknown. Here we describe
      how the analysis of the expression patterns of a well-conserved miRNA gene, mir
      57, at cellular resolution for every minute during early development of
      Caenorhabditis elegans provided key insights in understanding its function.
      Remarkably, mir-57 expression shows strong positional bias but little tissue
      specificity, a pattern reminiscent of Hox gene function. Despite the minor
      defects produced by a loss of function mutation, overexpression of mir-57 causes
      dramatic posterior defects, which also mimic the phenotypes of mutant alleles of
      a posterior Hox gene, nob-1, an Abd homolog. More importantly, nob-1 expression
      is found in the same two posterior AB sublineages as those expressing mir-57 but
      with an earlier onset. Intriguingly, nob-1 functions as an activator for mir-57
      expression; it is also a direct target of mir-57. In agreement with this, loss of
      mir-57 function partially rescues the nob-1 allele defects, indicating a negative
      feedback regulatory loop between the miRNA and Hox gene to provide positional
      cues. Given the conservation of the miRNA and Hox gene, the regulatory mechanism
      might be broadly used across species. The strategy used here to explore mir-57
      function provides a path to dissect the regulatory relationship between genes.

PMID- 20824073
TI  - Ctr2 links copper homeostasis to polysaccharide capsule formation and
      phagocytosis inhibition in the human fungal pathogen Cryptococcus neoformans.
AB  - Cryptococcus neoformans is a human opportunistic fungal pathogen responsible for
      approximately 1/3 of HIV/AIDS deaths worldwide. This budding yeast expresses a
      polysaccharide capsule necessary for virulence. Capsule production inhibits
      phagocytosis by macrophages. Here we describe results that link copper
      homeostasis to capsule production and the inhibition of phagocytosis.
      Specifically, using Agrobacterium-mediated insertional mutagenesis, we identified
      an insertion in the promoter region of the putative copper transporter-encoding
      gene CTR2 that results in reduced expression of CTR2 and increased phagocytosis
      by murine RAW264.7 macrophages. The mutant also displayed sensitivity to copper
      starvation and defects in polysaccharide capsule production and melanization.
      These defects were all reversed by genetic correction of the promoter insertion
      by homologous targeting. Several melanization-defective mutants identified
      previously, those in the RIM20, RIM101, and VPS25 genes, also display sensitivity
      to copper starvation, reduced capsule production and increased phagocytosis.
      Together these results indicate a previously undescribed link between copper
      homeostasis to polysaccharide capsule production and phagocytosis inhibition in
      Cryptococcus neoformans.

PMID- 20824074
TI  - Oral immunization with a live coxsackievirus/HIV recombinant induces gag p24
      specific T cell responses.
AB  - BACKGROUND: The development of an HIV/AIDS vaccine has proven to be elusive.
      Because human vaccine trials have not yet demonstrated efficacy, new vaccine
      strategies are needed for the HIV vaccine pipeline. We have been developing a new
      HIV vaccine platform using a live enterovirus, coxsackievirus B4 (CVB4) vector.
      Enteroviruses are ideal candidates for development as a vaccine vector for oral
      delivery, because these viruses normally enter the body via the oral route and
      survive the acidic environment of the stomach. METHODOLOGY/PRINCIPAL FINDINGS: We
      constructed a live coxsackievirus B4 recombinant, CVB4/p24(73(3)), that expresses
      seventy-three amino acids of the gag p24 sequence (HXB2) and assessed T cell
      responses after immunization of mice. The CVB4 recombinant was physically stable,
      replication-competent, and genetically stable. Oral or intraperitoneal
      immunization with the recombinant resulted in strong systemic gag p24-specific T
      cell responses as determined by the IFN-gamma ELISPOT assay and by multiparameter
      flow cytometry. Oral immunization with CVB4/p24(73(3)) resulted in a short-lived,
      localized infection of the gut without systemic spread. Because coxsackieviruses
      are ubiquitous in the human population, we also evaluated whether the recombinant
      was able to induce gag p24-specific T cell responses in mice pre-immunized with
      the CVB4 vector. We showed that oral immunization with CVB4/p24(73(3)) induced
      gag p24-specific immune responses in vector-immune mice.
      CONCLUSIONS/SIGNIFICANCE: The CVB4/p24(73(3)) recombinant retained the physical
      and biological characteristics of the parental CVB4 vector. Oral immunization
      with the CVB4 recombinant was safe and resulted in the induction of systemic HIV
      specific T cell responses. Furthermore, pre-existing vector immunity did not
      preclude the development of gag p24-specific T cell responses. As the search
      continues for new vaccine strategies, the present study suggests that live
      CVB4/HIV recombinants are potential new vaccine candidates for HIV.

PMID- 20824075
TI  - Fluorescent labeling of newborn dentate granule cells in GAD67-GFP transgenic
      mice: a genetic tool for the study of adult neurogenesis.
AB  - Neurogenesis in the adult hippocampus is an important form of structural
      plasticity in the brain. Here we report a line of BAC transgenic mice (GAD67-GFP
      mice) that selectively and transitorily express GFP in newborn dentate granule
      cells of the adult hippocampus. These GFP(+) cells show a high degree of
      colocalization with BrdU-labeled nuclei one week after BrdU injection and express
      the newborn neuron marker doublecortin and PSA-NCAM. Compared to mature dentate
      granule cells, these newborn neurons show immature morphological features:
      dendritic beading, fewer dendritic branches and spines. These GFP(+) newborn
      neurons also show immature electrophysiological properties: higher input
      resistance, more depolarized resting membrane potentials, small and non-typical
      action potentials. The bright labeling of newborn neurons with GFP makes it
      possible to visualize the details of dendrites, which reach the outer edge of the
      molecular layer, and their axon (mossy fiber) terminals, which project to the CA3
      region where they form synaptic boutons. GFP expression covers the whole
      developmental stage of newborn neurons, beginning within the first week of cell
      division and disappearing as newborn neurons mature, about 4 weeks postmitotic.
      Thus, the GAD67-GFP transgenic mice provide a useful genetic tool for studying
      the development and regulation of newborn dentate granule cells.

PMID- 20824076
TI  - Proteomic changes resulting from gene copy number variations in cancer cells.
AB  - Along the transformation process, cells accumulate DNA aberrations, including
      mutations, translocations, amplifications, and deletions. Despite numerous
      studies, the overall effects of amplifications and deletions on the end point of
      gene expression--the level of proteins--is generally unknown. Here we use large
      scale and high-resolution proteomics combined with gene copy number analysis to
      investigate in a global manner to what extent these genomic changes have a
      proteomic output and therefore the ability to affect cellular transformation. We
      accurately measure expression levels of 6,735 proteins and directly compare them
      to the gene copy number. We find that the average effect of these alterations on
      the protein expression is only a few percent. Nevertheless, by using a novel
      algorithm, we find the combined impact that many of these regional chromosomal
      aberrations have at the protein level. We show that proteins encoded by amplified
      oncogenes are often overexpressed, while adjacent amplified genes, which
      presumably do not promote growth and survival, are attenuated. Furthermore,
      regulation of biological processes and molecular complexes is independent of
      general copy number changes. By connecting the primary genome alteration to their
      proteomic consequences, this approach helps to interpret the data from large
      scale cancer genomics efforts.

PMID- 20824077
TI  - The histone H3K36 methyltransferase MES-4 acts epigenetically to transmit the
      memory of germline gene expression to progeny.
AB  - Methylation of histone H3K36 in higher eukaryotes is mediated by multiple
      methyltransferases. Set2-related H3K36 methyltransferases are targeted to genes
      by association with RNA Polymerase II and are involved in preventing aberrant
      transcription initiation within the body of genes. The targeting and roles of the
      NSD family of mammalian H3K36 methyltransferases, known to be involved in human
      developmental disorders and oncogenesis, are not known. We used genome-wide
      chromatin immunoprecipitation (ChIP) to investigate the targeting and roles of
      the Caenorhabditis elegans NSD homolog MES-4, which is maternally provided to
      progeny and is required for the survival of nascent germ cells. ChIP analysis in
      early C. elegans embryos revealed that, consistent with immunostaining results,
      MES-4 binding sites are concentrated on the autosomes and the leftmost
      approximately 2% (300 kb) of the X chromosome. MES-4 overlies the coding regions
      of approximately 5,000 genes, with a modest elevation in the 5' regions of gene
      bodies. Although MES-4 is generally found over Pol II-bound genes, analysis of
      gene sets with different temporal-spatial patterns of expression revealed that
      Pol II association with genes is neither necessary nor sufficient to recruit MES
      4. In early embryos, MES-4 associates with genes that were previously expressed
      in the maternal germ line, an interaction that does not require continued
      association of Pol II with those loci. Conversely, Pol II association with genes
      newly expressed in embryos does not lead to recruitment of MES-4 to those genes.
      These and other findings suggest that MES-4, and perhaps the related mammalian
      NSD proteins, provide an epigenetic function for H3K36 methylation that is novel
      and likely to be unrelated to ongoing transcription. We propose that MES-4
      transmits the memory of gene expression in the parental germ line to offspring
      and that this memory role is critical for the PGCs to execute a proper germline
      program.

PMID- 20824078
TI  - Comparative analysis of plasmids in the genus Listeria.
AB  - BACKGROUND: We sequenced four plasmids of the genus Listeria, including two novel
      plasmids from L. monocytogenes serotype 1/2c and 7 strains as well as one from
      the species L. grayi. A comparative analysis in conjunction with 10 published
      Listeria plasmids revealed a common evolutionary background. PRINCIPAL FINDINGS:
      All analysed plasmids share a common replicon-type related to theta-replicating
      plasmid pAMbeta1. Nonetheless plasmids could be broadly divided into two distinct
      groups based on replicon diversity and the genetic content of the respective
      plasmid groups. Listeria plasmids are characterized by the presence of a large
      number of diverse mobile genetic elements and a commonly occurring translesion
      DNA polymerase both of which have probably contributed to the evolution of these
      plasmids. We detected small non-coding RNAs on some plasmids that were homologous
      to those present on the chromosome of L. monocytogenes EGD-e. Multiple genes
      involved in heavy metal resistance (cadmium, copper, arsenite) as well as
      multidrug efflux (MDR, SMR, MATE) were detected on all listerial plasmids. These
      factors promote bacterial growth and survival in the environment and may have
      been acquired as a result of selective pressure due to the use of disinfectants
      in food processing environments. MDR efflux pumps have also recently been shown
      to promote transport of cyclic diadenosine monophosphate (c-di-AMP) as a secreted
      molecule able to trigger a cytosolic host immune response following infection.
      CONCLUSIONS: The comparative analysis of 14 plasmids of genus Listeria implied
      the existence of a common ancestor. Ubiquitously-occurring MDR genes on plasmids
      and their role in listerial infection now deserve further attention.

PMID- 20824079
TI  - Parent-of-origin effects in autism identified through genome-wide linkage
      analysis of 16,000 SNPs.
AB  - BACKGROUND: Autism is a common heritable neurodevelopmental disorder with complex
      etiology. Several genome-wide linkage and association scans have been carried out
      to identify regions harboring genes related to autism or autism spectrum
      disorders, with mixed results. Given the overlap in autism features with genetic
      abnormalities known to be associated with imprinting, one possible reason for
      lack of consistency would be the influence of parent-of-origin effects that may
      mask the ability to detect linkage and association. METHODS AND FINDINGS: We have
      performed a genome-wide linkage scan that accounts for potential parent-of-origin
      effects using 16,311 SNPs among families from the Autism Genetic Resource
      Exchange (AGRE) and the National Institute of Mental Health (NIMH) autism
      repository. We report parametric (GH, Genehunter) and allele-sharing linkage
      (Aspex) results using a broad spectrum disorder case definition. Paternal-origin
      genome-wide statistically significant linkage was observed on chromosomes 4
      (LOD(GH) = 3.79, empirical p<0.005 and LOD(Aspex) = 2.96, p = 0.008), 15 (LOD(GH)
      = 3.09, empirical p<0.005 and LOD(Aspex) = 3.62, empirical p = 0.003) and 20
      (LOD(GH) = 3.36, empirical p<0.005 and LOD(Aspex) = 3.38, empirical p = 0.006).
      CONCLUSIONS: These regions may harbor imprinted sites associated with the
      development of autism and offer fruitful domains for molecular investigation into
      the role of epigenetic mechanisms in autism.

PMID- 20824080
TI  - Temporo-spatial dynamics of event-related EEG beta activity during the initial
      contingent negative variation.
AB  - In the electroencephalogram (EEG), early anticipatory processes are accompanied
      by a slow negative potential, the initial contingent negative variation (iCNV),
      occurring between 500 and 1500 ms after cue onset over prefrontal cortical
      regions in tasks with cue-target intervals of about 3 s or longer. However, the
      temporal sequence of the distributed cortical activity contributing to iCNV
      generation remains unclear. During iCNV generation, selectively enhanced low-beta
      activity has been reported. Here we studied the temporal order of activation foci
      in cortical regions assumed to underlie iCNV generation using source
      reconstruction of low-beta (13-18 Hz) activity. During the iCNV, elicited by a
      cued simple reaction-time task, low-beta power peaked first (750 ms after cue
      onset) in anterior frontal and limbic regions and last (140 ms later) in
      posterior areas. This activity occurred 3300 ms before target onset and provides
      evidence for the temporally ordered involvement of both cognitive-control and
      motor-preparation processes already at early stages during the preparation for
      speeded action.

PMID- 20824081
TI  - Diversity of eukaryotic DNA replication origins revealed by genome-wide analysis
      of chromatin structure.
AB  - Eukaryotic DNA replication origins differ both in their efficiency and in the
      characteristic time during S phase when they become active. The biological basis
      for these differences remains unknown, but they could be a consequence of
      chromatin structure. The availability of genome-wide maps of nucleosome positions
      has led to an explosion of information about how nucleosomes are assembled at
      transcription start sites, but no similar maps exist for DNA replication origins.
      Here we combine high-resolution genome-wide nucleosome maps with comprehensive
      annotations of DNA replication origins to identify patterns of nucleosome
      occupancy at eukaryotic replication origins. On average, replication origins
      contain a nucleosome depleted region centered next to the ACS element, flanked on
      both sides by arrays of well-positioned nucleosomes. Our analysis identified DNA
      sequence properties that correlate with nucleosome occupancy at replication
      origins genome-wide and that are correlated with the nucleosome-depleted region.
      Clustering analysis of all annotated replication origins revealed a surprising
      diversity of nucleosome occupancy patterns. We provide evidence that the origin
      recognition complex, which binds to the origin, acts as a barrier element to
      position and phase nucleosomes on both sides of the origin. Finally, analysis of
      chromatin reconstituted in vitro reveals that origins are inherently nucleosome
      depleted. Together our data provide a comprehensive, genome-wide view of
      chromatin structure at replication origins and suggest a model of nucleosome
      positioning at replication origins in which the underlying sequence occludes
      nucleosomes to permit binding of the origin recognition complex, which then
      (likely in concert with nucleosome modifiers and remodelers) positions
      nucleosomes adjacent to the origin to promote replication origin function.

PMID- 20824082
TI  - Using evolutionary conserved modules in gene networks as a strategy to leverage
      high throughput gene expression queries.
AB  - BACKGROUND: Large-scale gene expression studies have not yielded the expected
      insight into genetic networks that control complex processes. These anticipated
      discoveries have been limited not by technology, but by a lack of effective
      strategies to investigate the data in a manageable and meaningful way. Previous
      work suggests that using a pre-determined seed-network of gene relationships to
      query large-scale expression datasets is an effective way to generate candidate
      genes for further study and network expansion or enrichment. Based on the
      evolutionary conservation of gene relationships, we test the hypothesis that a
      seed network derived from studies of retinal cell determination in the fly,
      Drosophila melanogaster, will be an effective way to identify novel candidate
      genes for their role in mouse retinal development. METHODOLOGY/PRINCIPAL
      FINDINGS: Our results demonstrate that a number of gene relationships regulating
      retinal cell differentiation in the fly are identifiable as pairwise correlations
      between genes from developing mouse retina. In addition, we demonstrate that our
      extracted seed-network of correlated mouse genes is an effective tool for
      querying datasets and provides a context to generate hypotheses. Our query
      identified 46 genes correlated with our extracted seed-network members.
      Approximately 54% of these candidates had been previously linked to the
      developing brain and 33% had been previously linked to the developing retina.
      Five of six candidate genes investigated further were validated by experiments
      examining spatial and temporal protein expression in the developing retina.
      CONCLUSIONS/SIGNIFICANCE: We present an effective strategy for pursuing a systems
      biology approach that utilizes an evolutionary comparative framework between two
      model organisms, fly and mouse. Future implementation of this strategy will be
      useful to determine the extent of network conservation, not just gene
      conservation, between species and will facilitate the use of prior biological
      knowledge to develop rational systems-based hypotheses.

PMID- 20824083
TI  - Formation of mobile chromatin-associated nuclear foci containing HIV-1 Vpr and
      VPRBP is critical for the induction of G2 cell cycle arrest.
AB  - HIV-1 Viral protein R (Vpr) induces a cell cycle arrest at the G2/M phase by
      activating the ATR DNA damage/stress checkpoint. Recently, we and several other
      groups showed that Vpr performs this activity by recruiting the DDB1-CUL4A
      (VPRBP) E3 ubiquitin ligase. While recruitment of this E3 ubiquitin ligase
      complex has been shown to be required for G2 arrest, the subcellular compartment
      where this complex forms and functionally acts is unknown. Herein, using
      immunofluorescence and confocal microscopy, we show that Vpr forms nuclear foci
      in several cell types including HeLa cells and primary CD4+ T-lymphocytes. These
      nuclear foci contain VPRBP and partially overlap with DNA repair foci components
      such as gamma-H2AX, 53BP1 and RPA32. While treatment with the non-specific ATR
      inhibitor caffeine or depletion of VPRBP by siRNA did not inhibit formation of
      Vpr nuclear foci, mutations in the C-terminal domain of Vpr and cytoplasmic
      sequestration of Vpr by overexpression of Gag-Pol resulted in impaired formation
      of these nuclear structures and defective G2 arrest. Consistently, we observed
      that G2 arrest-competent sooty mangabey Vpr could form these foci but not its G2
      arrest-defective paralog Vpx, suggesting that formation of Vpr nuclear foci
      represents a critical early event in the induction of G2 arrest. Indeed, we found
      that Vpr could associate to chromatin via its C-terminal domain and that it could
      form a complex with VPRBP on chromatin. Finally, analysis of Vpr nuclear foci by
      time-lapse microscopy showed that they were highly mobile and stable structures.
      Overall, our results suggest that Vpr recruits the DDB1-CUL4A (VPRBP) E3 ligase
      to these nuclear foci and uses these mobile structures to target a chromatin
      bound cellular substrate for ubiquitination in order to induce DNA
      damage/replication stress, ultimately leading to ATR activation and G2 cell cycle
      arrest.

PMID- 20824084
TI  - Community landscapes: an integrative approach to determine overlapping network
      module hierarchy, identify key nodes and predict network dynamics.
AB  - BACKGROUND: Network communities help the functional organization and evolution of
      complex networks. However, the development of a method, which is both fast and
      accurate, provides modular overlaps and partitions of a heterogeneous network,
      has proven to be rather difficult. METHODOLOGY/PRINCIPAL FINDINGS: Here we
      introduce the novel concept of ModuLand, an integrative method family determining
      overlapping network modules as hills of an influence function-based, centrality
      type community landscape, and including several widely used modularization
      methods as special cases. As various adaptations of the method family, we
      developed several algorithms, which provide an efficient analysis of weighted and
      directed networks, and (1) determine persvasively overlapping modules with high
      resolution; (2) uncover a detailed hierarchical network structure allowing an
      efficient, zoom-in analysis of large networks; (3) allow the determination of key
      network nodes and (4) help to predict network dynamics. CONCLUSIONS/SIGNIFICANCE:
      The concept opens a wide range of possibilities to develop new approaches and
      applications including network routing, classification, comparison and
      prediction.

PMID- 20824085
TI  - Amyloid-like aggregates of the yeast prion protein ure2 enter vertebrate cells by
      specific endocytotic pathways and induce apoptosis.
AB  - BACKGROUND: A number of amyloid diseases involve deposition of extracellular
      protein aggregates, which are implicated in mechanisms of cell damage and death.
      However, the mechanisms involved remain poorly understood. METHODOLOGY/PRINCIPAL
      FINDINGS: Here we use the yeast prion protein Ure2 as a generic model to
      investigate how amyloid-like protein aggregates can enter mammalian cells and
      convey cytotoxicity. The effect of three different states of Ure2 protein (native
      dimer, protofibrils and mature fibrils) was tested on four mammalian cell lines
      (SH-SY5Y, MES23.5, HEK-293 and HeLa) when added extracellularly to the medium.
      Immunofluorescence using a polyclonal antibody against Ure2 showed that all three
      protein states could enter the four cell lines. In each case, protofibrils
      significantly inhibited the growth of the cells in a dose-dependent manner,
      fibrils showed less toxicity than protofibrils, while the native state had no
      effect on cell growth. This suggests that the structural differences between the
      three protein states lead to their different effects upon cells. Protofibrils of
      Ure2 increased membrane conductivity, altered calcium homeostasis, and ultimately
      induced apoptosis. The use of standard inhibitors suggested uptake into mammalian
      cells might occur via receptor-mediated endocytosis. In order to investigate this
      further, we used the chicken DT40 B cell line DKOR, which allows conditional
      expression of clathrin. Uptake into the DKOR cell-line was reduced when clathrin
      expression was repressed suggesting similarities between the mechanism of PrP
      uptake and the mechanism observed here for Ure2. CONCLUSIONS/SIGNIFICANCE: The
      results provide insight into the mechanisms by which amyloid aggregates may cause
      pathological effects in prion and amyloid diseases.

PMID- 20824086
TI  - Structures of receptor complexes of a North American H7N2 influenza hemagglutinin
      with a loop deletion in the receptor binding site.
AB  - Human infections with subtype H7 avian influenza viruses have been reported as
      early as 1979. In 1996, a genetically stable 24-nucleotide deletion emerged in
      North American H7 influenza virus hemagglutinins, resulting in an eight amino
      acid deletion in the receptor-binding site. The continuous circulation of these
      viruses in live bird markets, as well as its documented ability to infect humans,
      raises the question of how these viruses achieve structural stability and
      functionality. Here we report a detailed molecular analysis of the receptor
      binding site of the North American lineage subtype H7N2 virus A/New York/107/2003
      (NY107), including complexes with an avian receptor analog (3'-sialyl-N
      acetyllactosamine, 3'SLN) and two human receptor analogs (6'-sialyl-N
      acetyllactosamine, 6'SLN; sialyllacto-N-tetraose b, LSTb). Structural results
      suggest a novel mechanism by which residues Arg220 and Arg229 (H3 numbering) are
      used to compensate for the deletion of the 220-loop and form interactions with
      the receptor analogs. Glycan microarray results reveal that NY107 maintains an
      avian-type (alpha2-3) receptor binding profile, with only moderate binding to
      human-type (alpha2-6) receptor. Thus despite its dramatically altered receptor
      binding site, this HA maintains functionality and confirms a need for continued
      influenza virus surveillance of avian and other animal reservoirs to define their
      zoonotic potential.

PMID- 20824087
TI  - Generation of covalently closed circular DNA of hepatitis B viruses via
      intracellular recycling is regulated in a virus specific manner.
AB  - Persistence of hepatitis B virus (HBV) infection requires covalently closed
      circular (ccc)DNA formation and amplification, which can occur via intracellular
      recycling of the viral polymerase-linked relaxed circular (rc) DNA genomes
      present in virions. Here we reveal a fundamental difference between HBV and the
      related duck hepatitis B virus (DHBV) in the recycling mechanism. Direct
      comparison of HBV and DHBV cccDNA amplification in cross-species transfection
      experiments showed that, in the same human cell background, DHBV but not HBV
      rcDNA converts efficiently into cccDNA. By characterizing the distinct forms of
      HBV and DHBV rcDNA accumulating in the cells we find that nuclear import,
      complete versus partial release from the capsid and complete versus partial
      removal of the covalently bound polymerase contribute to limiting HBV cccDNA
      formation; particularly, we identify genome region-selectively opened nuclear
      capsids as a putative novel HBV uncoating intermediate. However, the presence in
      the nucleus of around 40% of completely uncoated rcDNA that lacks most if not all
      of the covalently bound protein strongly suggests a major block further
      downstream that operates in the HBV but not DHBV recycling pathway. In summary,
      our results uncover an unexpected contribution of the virus to cccDNA formation
      that might help to better understand the persistence of HBV infection. Moreover,
      efficient DHBV cccDNA formation in human hepatoma cells should greatly facilitate
      experimental identification, and possibly inhibition, of the human cell factors
      involved in the process.

PMID- 20824088
TI  - Surface co-expression of two different PfEMP1 antigens on single plasmodium
      falciparum-infected erythrocytes facilitates binding to ICAM1 and PECAM1.
AB  - The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens play a
      major role in cytoadhesion of infected erythrocytes (IE), antigenic variation,
      and immunity to malaria. The current consensus on control of variant surface
      antigen expression is that only one PfEMP1 encoded by one var gene is expressed
      per cell at a time. We measured var mRNA transcript levels by real-time Q-PCR,
      analysed var gene transcripts by single-cell FISH and directly compared these
      with PfEMP1 antigen surface expression and cytoadhesion in three different
      antibody-selected P. falciparum 3D7 sub-lines using live confocal microscopy,
      flow cytometry and in vitro adhesion assays. We found that one selected parasite
      sub-line simultaneously expressed two different var genes as surface antigens, on
      single IE. Importantly, and of physiological relevance to adhesion and malaria
      pathogenesis, this parasite sub-line was found to bind both CD31/PECAM1 and
      CD54/ICAM1 and to adhere twice as efficiently to human endothelial cells,
      compared to infected cells having only one PfEMP1 variant on the surface. These
      new results on PfEMP1 antigen expression indicate that a re-evaluation of the
      molecular mechanisms involved in P. falciparum adhesion and of the accepted
      paradigm of absolutely mutually exclusive var gene transcription is required.

PMID- 20824089
TI  - NANOG reporter cell lines generated by gene targeting in human embryonic stem
      cells.
AB  - BACKGROUND: Pluripotency and self-renewal of human embryonic stem cells (hESCs)
      is mediated by a complex interplay between extra- and intracellular signaling
      pathways, which regulate the expression of pluripotency-specific transcription
      factors. The homeodomain transcription factor NANOG plays a central role in
      maintaining hESC pluripotency, but the precise role and regulation of NANOG are
      not well defined. METHODOLOGY/PRINCIPAL FINDINGS: To facilitate the study of
      NANOG expression and regulation in viable hESC cultures, we generated fluorescent
      NANOG reporter cell lines by gene targeting in hESCs. In these reporter lines,
      the fluorescent reporter gene was co-expressed with endogenous NANOG and
      responded to experimental induction or repression of the NANOG promoter with
      appropriate changes in expression levels. Furthermore, NANOG reporter lines
      facilitated the separation of hESC populations based on NANOG expression levels
      and their subsequent characterization. Gene expression arrays on isolated hESC
      subpopulations revealed genes with differential expression in NANOG(high) and
      NANOG(low) hESCs, providing candidates for NANOG downstream targets hESCs.
      CONCLUSION/SIGNIFICANCE: The newly derived NANOG reporter hESC lines present
      novel tools to visualize NANOG expression in viable hESCs. In future
      applications, these reporter lines can be used to elucidate the function and
      regulation of NANOG in pluripotent hESCs.

PMID- 20824090
TI  - HIV-1 gp41 and TCRalpha trans-membrane domains share a motif exploited by the HIV
      virus to modulate T-cell proliferation.
AB  - Viruses have evolved several strategies to modify cellular processes and evade
      the immune response in order to successfully infect, replicate, and persist in
      the host. By utilizing in-silico testing of a transmembrane sequence library
      derived from virus protein sequences, we have pin-pointed a nine amino-acid motif
      shared by a group of different viruses; this motif resembles the transmembrane
      domain of the alpha-subunit of the T-cell receptor (TCRalpha). The most striking
      similarity was found within the immunodeficiency virus (SIV and HIV) glycoprotein
      41 TMD (gp41 TMD). Previous studies have shown that stable interactions between
      TCRalpha and CD3 are localized to this nine amino acid motif within TCRalpha, and
      a peptide derived from it (TCRalpha TMD, GLRILLLKV) interfered and intervened in
      the TCR function when added exogenously. We now report that the gp41 TMD peptide
      co-localizes with CD3 within the TCR complex and inhibits T cell proliferation in
      vitro. However, the inhibitory mechanism of gp41 TMD differs from that of the
      TCRalpha TMD and also from the other two known immunosuppressive regions within
      gp41.

PMID- 20824091
TI  - Increased expression of bcl11b leads to chemoresistance accompanied by G1
      accumulation.
AB  - BACKGROUND: The expression of BCL11B was reported in T-cells, neurons and
      keratinocytes. Aberrations of BCL11B locus leading to abnormal gene transcription
      were identified in human hematological disorders and corresponding animal models.
      Recently, the elevated levels of Bcl11b protein have been described in a subset
      of squameous cell carcinoma cases. Despite the rapidly accumulating knowledge
      concerning Bcl11b biology, the contribution of this protein to normal or
      transformed cell homeostasis remains open. METHODOLOGY/PRINCIPAL FINDINGS: Here,
      by employing an overexpression strategy we revealed formerly unidentified
      features of Bcl11b. Two different T-cell lines were forced to express BCL11B at
      levels similar to those observed in primary T-cell leukemias. This resulted in
      markedly increased resistance to radiomimetic drugs while no influence on death
      receptor apoptotic pathway was observed. Apoptosis resistance triggered by BCL11B
      overexpression was accompanied by a cell cycle delay caused by accumulation of
      cells at G1. This cell cycle restriction was associated with upregulation of
      CDKN1C (p57) and CDKN2C (p18) cyclin dependent kinase inhibitors. Moreover, p27
      and p130 proteins accumulated and the SKP2 gene encoding a protein of the
      ubiquitin-binding complex responsible for their degradation was repressed.
      Furthermore, the expression of the MYCN oncogene was silenced which resulted in
      significant depletion of the protein in cells expressing high BCL11B levels. Both
      cell cycle restriction and resistance to DNA-damage-induced apoptosis coincided
      and required the histone deacetylase binding N-terminal domain of Bcl11b. The
      sensitivity to genotoxic stress could be restored by the histone deacetylase
      inhibitor trichostatine A. CONCLUSIONS: The data presented here suggest a
      potential role of BCL11B in tumor survival and encourage developing Bcl11b
      inhibitory approaches as a potential tool to specifically target chemoresistant
      tumor cells.

PMID- 20824092
TI  - Generation of neutralizing antibodies and divergence of SIVmac239 in cynomolgus
      macaques following short-term early antiretroviral therapy.
AB  - Neutralizing antibodies (NAb) able to react to heterologous viruses are generated
      during natural HIV-1 infection in some individuals. Further knowledge is required
      in order to understand the factors contributing to induction of cross-reactive
      NAb responses. Here a well-established model of experimental pathogenic infection
      in cynomolgus macaques, which reproduces long-lasting HIV-1 infection, was used
      to study the NAb response as well as the viral evolution of the highly
      neutralization-resistant SIVmac239. Twelve animals were infected intravenously
      with SIVmac239. Antiretroviral therapy (ART) was initiated ten days post
      inoculation and administered daily for four months. Viral load, CD4(+) T-cell
      counts, total IgG levels, and breadth as well as strength of NAb in plasma were
      compared simultaneously over 14 months. In addition, envs from plasma samples
      were sequenced at three time points in all animals in order to assess viral
      evolution. We report here that seven of the 12 animals controlled viremia to
      below 10(4) copies/ml of plasma after discontinuation of ART and that this
      control was associated with a low level of evolutionary divergence. Macaques that
      controlled viral load developed broader NAb responses early on. Furthermore,
      escape mutations, such as V67M and R751G, were identified in virus sequenced from
      all animals with uncontrolled viremia. Bayesian estimation of ancestral
      population genetic diversity (PGD) showed an increase in this value in non
      controlling or transient-controlling animals during the first 5.5 months of
      infection, in contrast to virus-controlling animals. Similarly, non- or transient
      controllers displayed more positively-selected amino-acid substitutions. An early
      increase in PGD, resulting in the generation of positively-selected amino-acid
      substitutions, greater divergence and relative high viral load after ART
      withdrawal, may have contributed to the generation of potent NAb in several
      animals after SIVmac239 infection. However, early broad NAb responses correlated
      with relatively preserved CD4(+) T-cell numbers, low viral load and limited viral
      divergence.

PMID- 20824093
TI  - Differential trafficking of oxidized LDL and oxidized LDL immune complexes in
      macrophages: impact on oxidative stress.
AB  - BACKGROUND: Oxidized low-density lipoproteins (oxLDL) and oxLDL-containing immune
      complexes (oxLDL-IC) contribute to formation of lipid-laden macrophages (foam
      cells). It has been shown that oxLDL-IC are considerably more efficient than
      oxLDL in induction of foam cell formation, inflammatory cytokines secretion, and
      cell survival promotion. Whereas oxLDL is taken up by several scavenger
      receptors, oxLDL-IC are predominantly internalized through the FCgamma receptor I
      (FCgamma RI). This study examined differences in intracellular trafficking of
      lipid and apolipoprotein moieties of oxLDL and oxLDL-IC and the impact on
      oxidative stress. METHODOLOGY/FINDINGS: Fluorescently labeled lipid and protein
      moieties of oxLDL co-localized within endosomal and lysosomal compartments in
      U937 human monocytic cells. In contrast, the lipid moiety of oxLDL-IC was
      detected in the endosomal compartment, whereas its apolipoprotein moiety advanced
      to the lysosomal compartment. Cells treated with oxLDL-IC prior to oxLDL
      demonstrated co-localization of internalized lipid moieties from both oxLDL and
      oxLDL-IC in the endosomal compartment. This sequential treatment likely inhibited
      oxLDL lipid moieties from trafficking to the lysosomal compartment. In RAW 264.7
      macrophages, oxLDL-IC but not oxLDL induced GFP-tagged heat shock protein 70
      (HSP70) and HSP70B', which co-localized with the lipid moiety of oxLDL-IC in the
      endosomal compartment. This suggests that HSP70 family members might prevent the
      degradation of the internalized lipid moiety of oxLDL-IC by delaying its
      advancement to the lysosome. The data also showed that mitochondrial membrane
      potential was decreased and generation of reactive oxygen and nitrogen species
      was increased in U937 cell treated with oxLDL compared to oxLDL-IC.
      CONCLUSIONS/SIGNIFICANCE: Findings suggest that lipid and apolipoprotein moieties
      of oxLDL-IC traffic to separate cellular compartments, and that HSP70/70B' might
      sequester the lipid moiety of oxLDL-IC in the endosomal compartment. This
      mechanism could ultimately influence macrophage function and survival.
      Furthermore, oxLDL-IC might regulate the intracellular trafficking of free oxLDL
      possibly through the induction of HSP70/70B'.

PMID- 20824094
TI  - Intracellular proton conductance of the hepatitis C virus p7 protein and its
      contribution to infectious virus production.
AB  - The hepatitis C virus (HCV) p7 protein is critical for virus production and an
      attractive antiviral target. p7 is an ion channel when reconstituted in
      artificial lipid bilayers, but channel function has not been demonstrated in vivo
      and it is unknown whether p7 channel activity plays a critical role in virus
      production. To evaluate the contribution of p7 to organelle pH regulation and
      virus production, we incorporated a fluorescent pH sensor within native,
      intracellular vesicles in the presence or absence of p7 expression. p7 increased
      proton (H(+)) conductance in vesicles and was able to rapidly equilibrate H(+)
      gradients. This conductance was blocked by the viroporin inhibitors amantadine,
      rimantadine and hexamethylene amiloride. Fluorescence microscopy using pH
      indicators in live cells showed that both HCV infection and expression of p7 from
      replicon RNAs reduced the number of highly acidic (pH<5) vesicles and increased
      lysosomal pH from 4.5 to 6.0. These effects were not present in uninfected cells,
      sub-genomic replicon cells not expressing p7, or cells electroporated with viral
      RNA containing a channel-inactive p7 point mutation. The acidification inhibitor,
      bafilomycin A1, partially restored virus production to cells electroporated with
      viral RNA containing the channel inactive mutation, yet did not in cells
      containing p7-deleted RNA. Expression of influenza M2 protein also complemented
      the p7 mutant, confirming a requirement for H(+) channel activity in virus
      production. Accordingly, exposure to acid pH rendered intracellular HCV particles
      non-infectious, whereas the infectivity of extracellular virions was acid stable
      and unaffected by incubation at low pH, further demonstrating a key requirement
      for p7-induced loss of acidification. We conclude that p7 functions as a H(+)
      permeation pathway, acting to prevent acidification in otherwise acidic
      intracellular compartments. This loss of acidification is required for productive
      HCV infection, possibly through protecting nascent virus particles during an as
      yet uncharacterized maturation process.

PMID- 20824095
TI  - Suppression of lung tumorigenesis by leucine zipper/EF hand-containing
      transmembrane-1.
AB  - BACKGROUND: Leucine zipper/EF hand-containing transmembrane-1 (LETM1) encodes for
      the human homologue of yeast Mdm38p, which is a mitochondria-shaping protein of
      unclear function. However, a previous study demonstrated that LETM1 served as an
      anchor protein for complex formation between mitochondria and ribosome, and
      regulated mitochondrial biogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Therefore, we
      examine the possibility that LETM1 may function to regulate mitochondria and lung
      tumor growth. In this study, we addressed this question by studying in the effect
      of adenovirus-mediated LETM1 in the lung cancer cell and lung cancer model mice.
      To investigate the effects of adenovirus-LETM1 in vitro, we infected with
      adenovirus-LETM1 in A549 cells. Additionally, in vivo effects of LETM1 were
      evaluated on K-ras(LA1) mice, human non-small cell lung cancer model mice, by
      delivering the LETM1 via aerosol through nose-only inhalation system. The effects
      of LETM1 on lung cancer growth and AMPK related signals were evaluated.
      Adenovirus-mediated overexpression of LETM1 could induce destruction of
      mitochondria of lung cancer cells through depleting ATP and AMPK activation.
      Furthermore, adenoviral-LETM1 also altered Akt signaling and inhibited the cell
      cycle while facilitating apoptosis. Theses results demonstrated that adenovirus
      LETM1 suppressed lung cancer cell growth in vitro and in vivo.
      CONCLUSIONS/SIGNIFICANCE: Adenovirus-mediated LETM1 may provide a useful target
      for designing lung tumor prevention and treatment.

PMID- 20824096
TI  - The distribution of GYR- and YLP-like motifs in Drosophila suggests a general
      role in cuticle assembly and other protein-protein interactions.
AB  - BACKGROUND: Arthropod cuticle is composed predominantly of a self-assembling
      matrix of chitin and protein. Genes encoding structural cuticular proteins are
      remarkably abundant in arthropod genomes, yet there has been no systematic survey
      of conserved motifs across cuticular protein families. METHODOLOGY/PRINCIPAL
      FINDINGS: Two short sequence motifs with conserved tyrosines were identified in
      Drosophila cuticular proteins that were similar to the GYR and YLP Interpro
      domains. These motifs were found in members of the CPR, Tweedle, CPF/CPFL, and
      (in Anopheles gambiae) CPLCG cuticular protein families, and the Dusky/Miniature
      family of cuticle-associated proteins. Tweedle proteins have a characteristic
      motif architecture that is shared with the Drosophila protein GCR1 and its
      orthologs in other species, suggesting that GCR1 is also cuticular. A resilin
      repeat, which has been shown to confer elasticity, matched one of the motifs; a
      number of other Drosophila proteins of unknown function exhibit a motif
      architecture similar to that of resilin. The motifs were also present in some
      proteins of the peritrophic matrix and the eggshell, suggesting molecular
      convergence among distinct extracellular matrices. More surprisingly, gene
      regulation, development, and proteolysis were statistically over-represented
      ontology terms for all non-cuticular matches in Drosophila. Searches against
      other arthropod genomes indicate that the motifs are taxonomically widespread.
      CONCLUSIONS: This survey suggests a more general definition for GYR and YLP
      motifs and reveals their contribution to several types of extracellular matrix.
      They may define sites of protein interaction with DNA or other proteins, based on
      ontology analysis. These results can help guide experimental studies on the
      biochemistry of cuticle assembly.

PMID- 20824098
TI  - Myeloid differentiation factor 88 (MyD88)-deficiency increases risk of diabetes
      in mice.
AB  - BACKGROUND: Multiple lines of evidence suggest innate immune response pathways to
      be involved in the development of obesity-associated diabetes although the
      molecular mechanism underling the disease is unknown. Recent observations suggest
      that saturated fatty acids can act as a ligand for toll-like receptor (TLR) 4,
      which is thought to mediate obesity-associated insulin resistance. Myeloid
      differentiation factor 88 (MyD88) is an adapter protein for TLR/IL-1 receptor
      signaling, which is involved in the activation of inflammatory pathways. To
      evaluate molecular mechanisms linking obesity-associated diabetes down-stream of
      TLR4, we investigated physiological role of MyD88 in high-fat diet (HFD)-induced
      obesity. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we found MyD88
      deficient mice fed a HFD had increased circulating levels of insulin, leptin and
      cholesterol, as well as liver dysfunction (increased induction of ALT levels,
      increased activation of JNK and cleavage of PARP), which were linked to the onset
      of severe diabetes. On the other hand, TNF-alpha would not be involved in HFD
      induced diabetes in MyD88-deficient mice, because TNF-alpha level was attenuated
      in MyD88-deficient mice fed with HFD. CONCLUSIONS/SIGNIFICANCE: The present
      finding of an unexpected role for MyD88 in preventing diabetes may provide a
      potential novel target/strategy for treating metabolic syndrome.

PMID- 20824097
TI  - Two genes on A/J chromosome 18 are associated with susceptibility to
      Staphylococcus aureus infection by combined microarray and QTL analyses.
AB  - Although it has recently been shown that A/J mice are highly susceptible to
      Staphylococcus aureus sepsis as compared to C57BL/6J, the specific genes
      responsible for this differential phenotype are unknown. Using chromosome
      substitution strains (CSS), we found that loci on chromosomes 8, 11, and 18
      influence susceptibility to S. aureus sepsis in A/J mice. We then used two
      candidate gene selection strategies to identify genes on these three chromosomes
      associated with S. aureus susceptibility, and targeted genes identified by both
      gene selection strategies. First, we used whole genome transcription profiling to
      identify 191 (56 on chr. 8, 100 on chr. 11, and 35 on chr. 18) genes on our three
      chromosomes of interest that are differentially expressed between S. aureus
      infected A/J and C57BL/6J. Second, we identified two significant quantitative
      trait loci (QTL) for survival post-infection on chr. 18 using N(2) backcross mice
      (F(1) [C18A]xC57BL/6J). Ten genes on chr. 18 (March3, Cep120, Chmp1b, Dcp2,
      Dtwd2, Isoc1, Lman1, Spire1, Tnfaip8, and Seh1l) mapped to the two significant
      QTL regions and were also identified by the expression array selection strategy.
      Using real-time PCR, 6 of these 10 genes (Chmp1b, Dtwd2, Isoc1, Lman1, Tnfaip8,
      and Seh1l) showed significantly different expression levels between S. aureus
      infected A/J and C57BL/6J. For two (Tnfaip8 and Seh1l) of these 6 genes, siRNA
      mediated knockdown of gene expression in S. aureus-challenged RAW264.7
      macrophages induced significant changes in the cytokine response (IL-1 beta and
      GM-CSF) compared to negative controls. These cytokine response changes were
      consistent with those seen in S. aureus-challenged peritoneal macrophages from
      CSS 18 mice (which contain A/J chromosome 18 but are otherwise C57BL/6J), but not
      C57BL/6J mice. These findings suggest that two genes, Tnfaip8 and Seh1l, may
      contribute to susceptibility to S. aureus in A/J mice, and represent promising
      candidates for human genetic susceptibility studies.

PMID- 20824099
TI  - The canine papillomavirus and gamma HPV E7 proteins use an alternative domain to
      bind and destabilize the retinoblastoma protein.
AB  - The high-risk HPV E6 and E7 proteins cooperate to immortalize primary human
      cervical cells and the E7 protein can independently transform fibroblasts in
      vitro, primarily due to its ability to associate with and degrade the
      retinoblastoma tumor suppressor protein, pRb. The binding of E7 to pRb is
      mediated by a conserved Leu-X-Cys-X-Glu (LXCXE) motif in the conserved region 2
      (CR2) of E7 and this domain is both necessary and sufficient for E7/pRb
      association. In the current study, we report that the E7 protein of the
      malignancy-associated canine papillomavirus type 2 encodes an E7 protein that has
      serine substituted for cysteine in the LXCXE motif. In HPV, this substitution in
      E7 abrogates pRb binding and degradation. However, despite variation at this
      critical site, the canine papillomavirus E7 protein still bound and degraded pRb.
      Even complete deletion of the LXSXE domain of canine E7 failed to interfere with
      binding to pRb in vitro and in vivo. Rather, the dominant binding site for pRb
      mapped to the C-terminal domain of canine E7. Finally, while the CR1 and CR2
      domains of HPV E7 are sufficient for degradation of pRb, the C-terminal region of
      canine E7 was also required for pRb degradation. Screening of HPV genome
      sequences revealed that the LXSXE motif of the canine E7 protein was also present
      in the gamma HPVs and we demonstrate that the gamma HPV-4 E7 protein also binds
      pRb in a similar way. It appears, therefore, that the type 2 canine PV and gamma
      type HPVs not only share similar properties with respect to tissue specificity
      and association with immunosuppression, but also the mechanism by which their E7
      proteins interact with pRb.

PMID- 20824100
TI  - Mapracorat, a novel selective glucocorticoid receptor agonist, inhibits
      hyperosmolar-induced cytokine release and MAPK pathways in human corneal
      epithelial cells.
AB  - PURPOSE: Increasing evidence suggests that tear hyperosmolarity is a central
      mechanism causing ocular surface inflammation and damage in dry eye disease.
      Mapracorat (BOL-303242-X) is a novel glucocorticoid receptor agonist currently
      under clinical evaluation for use in the treatment of dry eye disease. This study
      assessed the anti-inflammatory effects of mapracorat in an in vitro osmotic
      stress model which mimics some of the pathophysiological changes seen in dry eye.
      METHODS: Human corneal epithelial cells were cultured in normal osmolar media
      (317 mOsM) or 440 mOsM hyperosmolar media for 24 h. Luminex technology was used
      to determine the effect of mapracorat on hyperosmolar-induced cytokine release.
      Effects of mapracorat on mitogen-activated protein kinase (MAPK) phosphorylation
      were determined by cell based ELISA. Effects of mapracorat on nuclear factor
      kappa B (NFkappaB) and activator protein-1 (AP-1) transcriptional activity were
      assessed by reporter gene assay. Dexamethasone was used as a control. RESULTS:
      Hyperosmolar conditions induced release of the pro-inflammatory cytokines
      interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemotactic protein-1
      (MCP-1) from cultured human corneal epithelial cells, and altered the
      phosphorylation state of p38 and c-Jun N-terminal kinase (JNK) and
      transcriptional activity of NFkappaB and AP-1. Incubation of cells with
      mapracorat inhibited hyperosmolar-induced cytokine release with comparable
      activity and potency as dexamethasone. This inhibition was reversed by the
      glucocorticoid receptor antagonist mifepristone (RU-486). Increased
      phosphorylation of p38 and JNK caused by hyperosmolarity was inhibited by
      mapracorat. Mapracorat also significantly decreased the hyperosmolar-induced
      increase in NFkappaB and AP-1 transcriptional activity. CONCLUSIONS: Mapracorat
      acts as a potent anti-inflammatory agent in corneal epithelial cells challenged
      with osmotic stress, with comparable activity to the traditional steroid
      dexamethasone. These in vitro data suggest that mapracorat may be efficacious in
      the treatment of dry eye disease.

PMID- 20824101
TI  - Improving public health training and research capacity in Africa: a replicable
      model for linking training to health and socio-demographic surveillance data.
AB  - BACKGROUND: Research training for public health professionals is key to the
      future of public health and policy in Africa. A growing number of schools of
      public health are connected to health and socio-demographic surveillance system
      field sites in developing countries, in Africa and Asia in particular. Linking
      training programs with these sites provides important opportunities to improve
      training, build local research capacity, foreground local health priorities, and
      increase the relevance of research to local health policy. OBJECTIVE: To increase
      research training capacity in public health programs by providing targeted
      training to students and increasing the accessibility of existing data. DESIGN:
      This report is a case study of an approach to linking public health research and
      training at the University of the Witwatersrand. We discuss the development of a
      sample training database from the Agincourt Health and Socio-demographic
      Surveillance System in South Africa and outline a concordant transnational
      intensive short course on longitudinal data analysis offered by the University of
      the Witwatersrand and the University of Colorado-Boulder. This case study
      highlights ways common barriers to linking research and training can be overcome.
      RESULTS AND CONCLUSIONS: This collaborative effort demonstrates that linking
      training to ongoing data collection can improve student research, accelerate
      student training, and connect students to an international network of scholars.
      Importantly, the approach can be adapted to other partnerships between schools of
      public health and longitudinal research sites.

PMID- 20824103
TI  - Frequency analysis techniques for identification of viral genetic data.
AB  - Environmental metagenomic samples and samples obtained as an attempt to identify
      a pathogen associated with the emergence of a novel infectious disease are
      important sources of novel microorganisms. The low costs and high throughput of
      sequencing technologies are expected to allow for the genetic material in those
      samples to be sequenced and the genomes of the novel microorganisms to be
      identified by alignment to those in a database of known genomes. Yet, for various
      biological and technical reasons, such alignment might not always be possible. We
      investigate a frequency analysis technique which on one hand allows for the
      identification of genetic material without relying on alignment and on the other
      hand makes possible the discovery of nonoverlapping contigs from the same
      organism. The technique is based on obtaining signatures of the genetic data and
      defining a distance/similarity measure between signatures. More precisely, the
      signatures of the genetic data are the frequencies of k-mers occurring in them,
      with k being a natural number. We considered an entropy-based distance between
      signatures, similar to the Kullback-Leibler distance in information theory, and
      investigated its ability to categorize negative-sense single-stranded RNA (ssRNA)
      viral genetic data. Our conclusion is that in this viral context, the technique
      provides a viable way of discovering genetic relationships without relying on
      alignment. We envision that our approach will be applicable to other microbial
      genetic contexts, e.g., other types of viruses, and will be an important tool in
      the discovery of novel microorganisms.

PMID- 20824102
TI  - Economical evolution: microbes reduce the synthetic cost of extracellular
      proteins.
AB  - Protein evolution is not simply a race toward improved function. Because
      organisms compete for limited resources, fitness is also affected by the relative
      economy of an organism's proteome. Indeed, many abundant proteins contain
      relatively high percentages of amino acids that are metabolically less taxing for
      the cell to make, thus reducing cellular cost. However, not all abundant proteins
      are economical, and many economical proteins are not particularly abundant. Here
      we examined protein composition and found that the relative synthetic cost of
      amino acids constrains the composition of microbial extracellular proteins. In
      Escherichia coli, extracellular proteins contain, on average, fewer energetically
      expensive amino acids independent of their abundance, length, function, or
      structure. Economic pressures have strategically shaped the amino acid
      composition of multicomponent surface appendages, such as flagella, curli, and
      type I pili, and extracellular enzymes, including type III effector proteins and
      secreted serine proteases. Furthermore, in silico analysis of Pseudomonas
      syringae, Mycobacterium tuberculosis, Saccharomyces cerevisiae, and over 25 other
      microbes spanning a wide range of GC content revealed a broad bias toward more
      economical amino acids in extracellular proteins. The synthesis of any protein,
      especially those rich in expensive aromatic amino acids, represents a significant
      investment. Because extracellular proteins are lost to the environment and not
      recycled like other cellular proteins, they present a greater burden on the cell,
      as their amino acids cannot be reutilized during translation. We hypothesize that
      evolution has optimized extracellular proteins to reduce their synthetic burden
      on the cell.

PMID- 20824104
TI  - Interactions of the transmembrane polymeric rings of the Salmonella enterica
      serovar Typhimurium type III secretion system.
AB  - The type III secretion system (T3SS) is an interspecies protein transport machine
      that plays a major role in interactions of Gram-negative bacteria with animals
      and plants by delivering bacterial effector proteins into host cells. T3SSs span
      both membranes of Gram-negative bacteria by forming a structure of connected
      oligomeric rings termed the needle complex (NC). Here, the localization of
      subunits in the Salmonella enterica serovar Typhimurium T3SS NC were probed via
      mass spectrometry-assisted identification of chemical cross-links in intact NC
      preparations. Cross-links between amino acids near the amino terminus of the
      outer membrane ring component InvG and the carboxyl terminus of the inner
      membrane ring component PrgH and between the two inner membrane components PrgH
      and PrgK allowed for spatial localization of the three ring components within the
      electron density map structures of NCs. Mutational and biochemical analysis
      demonstrated that the amino terminus of InvG and the carboxyl terminus of PrgH
      play a critical role in the assembly and function of the T3SS apparatus. Analysis
      of an InvG mutant indicates that the structure of the InvG oligomer can affect
      the switching of the T3SS substrate to translocon and effector components. This
      study provides insights into how structural organization of needle complex base
      components promotes T3SS assembly and function.

PMID- 20824105
TI  - Emergence and global dissemination of host-specific Streptococcus agalactiae
      clones.
AB  - To examine the global diversity of Streptococcus agalactiae (group B streptococci
      [GBS]) and to elucidate the evolutionary processes that determine its population
      genetics structure and the reported changes in host tropism and infection
      epidemiology, we examined a collection of 238 bovine and human isolates from nine
      countries on five continents. Phylogenetic analysis based on the sequences of 15
      housekeeping genes combined with patterns of virulence-associated traits
      identified a genetically heterogeneous core population from which virulent
      lineages occasionally emerge as a result of recombination affecting major
      segments of the genome. Such lineages, like clonal complex 17 (CC17) and two
      distinct clusters of CC23, are exclusively adapted to either humans or cattle and
      successfully spread globally. The recent emergence and expansion of the human
      associated and highly virulent sequence type 17 (ST17) could conceivably account,
      in part, for the increased prevalence of neonatal GBS infections after 1960. The
      composite structure of the S. agalactiae genome invalidates phylogenetic
      inferences exclusively based on multilocus sequence typing (MLST) data and
      thereby the previously reported conclusion that the human-associated CC17 emerged
      from the bovine-associated CC67.

PMID- 20824106
TI  - Membrane topology mapping of the O-antigen flippase (Wzx), polymerase (Wzy), and
      ligase (WaaL) from Pseudomonas aeruginosa PAO1 reveals novel domain
      architectures.
AB  - Biosynthesis of B-band lipopolysaccharide (LPS) in Pseudomonas aeruginosa follows
      the Wzy-dependent pathway, requiring the integral inner membrane proteins Wzx (O
      antigen [O-Ag] flippase), Wzy (O-Ag polymerase), and WaaL (O-Ag ligase). For an
      important first step in deciphering the mechanisms of LPS assembly, we set out to
      map the membrane topology of these proteins. Random and targeted 3'wzx, wzy, and
      waaL truncations were fused to a phoA-lacZalpha dual reporter capable of
      displaying both alkaline phosphatase and beta-galactosidase activity. The results
      from truncation fusion expression and the corresponding differential enzyme
      activity ratios allowed for the assignment of specific regions of the proteins to
      cytoplasmic, transmembrane (TM), or periplasmic loci. Protein orientation in the
      inner membrane was confirmed via C-terminal fusion to green fluorescent protein.
      Our data revealed unique TM domain properties in these proteins, particularly for
      Wzx, indicating the potential for a charged pore. Novel periplasmic and
      cytoplasmic loop domains were also uncovered, with the latter in Wzy and WaaL
      revealing tracts consistent with potential Walker A/B motifs.

PMID- 20824108
TI  - Florida Red Tide Perception: Residents versus Tourists.
AB  - The west coast of Florida has annual blooms of the toxin-producing
      dinoflagellate, Karenia brevis with Sarasota, FL considered the epicenter for
      these blooms. Numerous outreach materials, including Frequently Asked Question
      (FAQ) cards, exhibits for local museums and aquaria, public beach signs, and
      numerous websites have been developed to disseminate information to the public
      about this natural hazard. In addition, during intense onshore blooms, a great
      deal of media attention, primarily via newspaper (print and web) and television,
      is focused on red tide. However to date, the only measure of effectiveness of
      these outreach methods has been counts of the number of people exposed to the
      information, e.g., visits to a website or number of FAQ cards distributed. No
      formal assessment has been conducted to determine if these materials meet their
      goal of informing the public about Florida red tide. Also, although local
      residents have the opinion that they are very knowledgeable about Florida red
      tide, this has not been verified empirically. This study addressed these issues
      by creating and administering an evaluation tool for the assessment of public
      knowledge about Florida red tide. A focus group of Florida red tide outreach
      developers assisted in the creation of the evaluation tool. The location of the
      evaluation was the west coast of Florida, in Sarasota County. The objective was
      to assess the knowledge of the general public about Florida red tide. This
      assessment identified gaps in public knowledge regarding Florida red tides and
      also identified what information sources people want to use to obtain information
      on Florida red tide. The results from this study can be used to develop more
      effective outreach materials on Florida red tide.

PMID- 20824107
TI  - The ubiquitous conserved glycopeptidase Gcp prevents accumulation of toxic
      glycated proteins.
AB  - Amadori-modified proteins (AMPs) are the products of nonenzymatic glycation
      formed by reaction of reducing sugars with primary amine-containing amino acids
      and can develop into advanced glycated end products (AGEs), highly stable toxic
      compounds. AGEs are known to participate in many age-related human diseases,
      including cardiovascular, neurological, and liver diseases. The metabolism of
      these glycated proteins is not yet understood, and the mechanisms that reduce
      their accumulation are not known so far. Here, we show for Escherichia coli that
      a conserved glycopeptidase (Gcp, also called Kae1), which is encoded by nearly
      every sequenced genome in the three domains of life, prevents the accumulation of
      Amadori products and AGEs. Using mutants, we show that Gcp depletion results in
      accumulation of AMPs and eventually leads to the accumulation of AGEs. We
      demonstrate that Gcp binds to glycated proteins, including pyruvate
      dehydrogenase, previously shown to be a glycation-prone enzyme. Our experiments
      also show that the severe phenotype of Gcp depletion can be relieved under
      conditions of low intracellular glycation. As glycated proteins are ubiquitous,
      the involvement of Gcp in the metabolism of AMPs and AGEs is likely to have been
      conserved in evolution, suggesting a universal involvement of Gcp in cellular
      aging and explaining the essentiality of Gcp in many organisms.

PMID- 20824109
TI  - Undocumented Migration from Latin America in an Era of Rising U.S. Enforcement.
AB  - Available data have consistently pointed up the failure of U.S. policies to
      reduce undocumented migration from Latin America. To shed light on the reasons
      for this failure, we estimated a series of dynamic models of undocumented entry
      into and exit from the United States. Our estimates suggest that undocumented
      migration is grounded more in mechanisms posited by social capital theory and the
      new economics of labor migration rather than neoclassical economics. As a result,
      U.S. efforts to increase the costs of undocumented entry and reduce the benefits
      of undocumented labor have proven unsuccessful given the widespread access of
      Latin Americans to migrant networks. The main effect of U.S. enforcement efforts
      has been to reduce the circularity of Latin American migration.

PMID- 20824110
TI  - Manipulation of Suspended Single Cells by Microfluidics and Optical Tweezers.
AB  - Chondrocytes and osteoblasts experience multiple stresses in vivo. The optimum
      mechanical conditions for cell health are not fully understood. This paper
      describes the optical and microfluidic mechanical manipulation of single
      suspended cells enabled by the MUPIVOT, an integrated micron resolution particle
      image velocimeter (MUPIV) and dual optical tweezers instrument (OT). In this
      study, we examine the viability and trap stiffness of cartilage cells, identify
      the maximum fluid-induced stresses possible in uniform and extensional flows, and
      compare the deformation characteristics of bone and muscle cells. These results
      indicate cell photodamage of chondrocytes is negligible for at least 20 min for
      laser powers below 30 mW, a dead cell presents less resistance to internal
      organelle rearrangement and deforms globally more than a viable cell, the maximum
      fluid-induced shear stresses are limited to ~15 mPa for uniform flows but may
      exceed 1 Pa for extensional flows, and osteoblasts show no deformation for shear
      stresses up to 250 mPa while myoblasts are more easily deformed and exhibit a
      modulated response to increasing stress. This suggests that global and/or local
      stresses can be applied to single cells without physical contact. Coupled with
      microfluidic sensors, these manipulations may provide unique methods to explore
      single cell biomechanics.

PMID- 20824111
TI  - A protein sequence meta-functional signature for calcium binding residue
      prediction.
AB  - The diversity of characterized protein functions found amongst experimentally
      interrogated proteins suggests that a vast array of unknown functions remains
      undiscovered. These protein functions are imparted by specific geometric
      distributions of amino acid residue chemical moieties, each contributing a
      functional interaction. We hypothesize that individual residue function
      contributions are predictable through sequence analytic knowledge based
      algorithms, and that they can be recombined to understand composite protein
      function by predicting spatial relation in tertiary structure. We assess the
      former by training a meta-functional signature algorithm to specifically predict
      calcium ion binding residues from protein sequence. We estimate the latter by
      testing for match between predictive contribution of positions in predicted
      secondary structures and patterns of side chain proximity forced by secondary
      structure moieties. Specific training for calcium binding results in 83% area
      under the receiver operator characteristic curve added value over random (AUCoR)
      and p<10(-300) significance as measured by Kendall's tau in ten fold cross
      validation for parallel sets of 811 residues in 336 proteins and 696 residues in
      299 proteins. Training for generalized function results in 63% AUCoR and p?10(
      221) for the same tests. Including inference of side chain proximity improves
      predictive ability by 2% AUCoR consistently. The results demonstrate that protein
      meta-functional signatures can be trained to predict specific protein functions
      by considering amino acid identity and structural features accessible from
      sequence, laying the groundwork for composite sequence based function site
      prediction.

PMID- 20824112
TI  - Implementation of a Relationship-Based School Readiness Intervention: A
      Multidimensional Approach to Fidelity Measurement for Early Childhood.
AB  - The implementation efforts of 65 early childhood professionals involved in the
      Getting Ready project, an integrated, multi-systemic intervention that promotes
      school readiness through parent engagement for children from birth to age five,
      were investigated. Digital videotaped records of professionals engaged in home
      visits with families across both treatment and comparison conditions were coded
      objectively using a partial-interval recording system to identify and record
      early childhood professionals' implementation of intervention strategies and
      their effectiveness in promoting parent engagement and interest in their child.
      Adherence, quality of intervention delivery, differentiation between groups, and
      participant responsiveness were assessed as multiple dimensions of fidelity.
      Early childhood professionals in the treatment group relative to the comparison
      group demonstrated greater frequency of adherence to some intervention
      strategies, as well as higher rates of total strategy use. In addition,
      significant positive relationships were found between years of experience,
      education and quality of intervention delivery. Quality of intervention delivery
      was different by program type (Early Head Start versus Head Start). Adherence in
      the treatment group was correlated with the rate of contact between parent and
      early childhood professional during the home visit.

PMID- 20824113
TI  - Interplay of mechanical and binding properties of Fibronectin type I.
AB  - Fibronectins (FNs) are a major component of the extracellular matrix (ECM), and
      provide important binding sites for a variety of ligands outside and on the
      surface of the cell. Similar to other ECM proteins, FNs are consistently subject
      to mechanical stress in the ECM. Therefore, it is important to study their
      structure and binding properties under mechanical stress and understand how their
      binding and mechanical properties might affect each other. Although certain FN
      modules have been extensively investigated, no simulation studies have been
      reported for the FN type I (Fn1) domains, despite their prominent role in binding
      of various protein modules to FN polymers in the ECM. Using equilibrium and
      steered molecular dynamics simulations, we have studied mechanical properties of
      Fn1 modules in the presence or the absence of a specific FN-binding peptide
      (FnBP). We have also investigated how the binding of the FnBP peptide to Fn1
      might be affected by tensile force. Despite the presence of disulfide bonds
      within individual Fn1 modules that are presumed to prevent their extension, it is
      found that significant internal structural changes within individual modules are
      induced by the forces applied in our simulations. These internal structural
      changes result in significant variations in the accessibility of different
      residues of the Fn1 modules, which affect their exposure, and, thus, the binding
      properties of the Fn1 modules. Binding of the FnBP appears to reduce the
      flexibility of the linker region connecting individual Fn1 modules (exhibited in
      the form of reduced fluctuation and motion of the linker region), both with
      regard to bending and stretching motions, and hence stabilizes the inter-domain
      configuration under force. Under large tensile forces, the FnBP peptide unbinds
      from Fn1. The results suggest that Fn1 modules in FN polymers do contribute to
      the overall extension caused by force-induced stretching of the polymer in the
      ECM, and that binding properties of Fn1 modules can be affected by mechanically
      induced internal protein conformational changes in spite of the presence of
      disulfide bonds which were presumed to completely abolish the capacity of Fn1
      modules to undergo extension in response to external forces.

PMID- 20824115
TI  - Registration of cortical surfaces using sulcal landmarks for group analysis of
      MEG data.
AB  - We present a method to register individual cortical surfaces to a surface-based
      brain atlas or canonical template using labeled sulcal curves as landmark
      constraints. To map one cortex smoothly onto another, we minimize a thin-plate
      spline energy defined on the surface by solving the associated partial
      differential equations (PDEs). By using covariant derivatives in solving these
      PDEs, we compute the bending energy with respect to the intrinsic geometry of the
      3D surface rather than evaluating it in the flattened metric of the 2D parameter
      space. This covariant approach greatly reduces the confounding effects of the
      surface parameterization on the resulting registration.

PMID- 20824114
TI  - Review of Interventions for Parental Depression from Toddlerhood to Adolescence.
AB  - Because of the recurrent course, significant burden, and intergenerational impact
      of depression, there is a great need for interventions for depressed parents and
      their children. This article reviews eight interventions that 1) aim to impact
      the functioning and well-being of 18-month to 18-year old children of depressed
      parents and 2) have been evaluated in controlled studies. The interventions are
      described and the empirical evidence of their efficacy is reviewed and critiqued.
      Existing research points to several promising intervention strategies, such as
      psychoeducation about parental depression, addressing parenting in adult
      depression treatment, promoting positive parent-child interactions, and teaching
      coping skills to children. Common limitations of the research in this area are
      small sample sizes, homogenous samples, and lack of replication. Implementation
      problems within the mental healthcare system are highlighted. Multi-component
      interventions seem to be a promising approach to address the complex impact
      parental depression has on children and the parent-child relationship. This
      review illustrates the need for more research on intervention models that can be
      implemented with children at various developmental levels.

PMID- 20824116
TI  - Giant Magnetoresistive Sensors for DNA Microarray.
AB  - Giant magnetoresistive (GMR) sensors are developed for a DNA microarray. Compared
      with the conventional fluorescent sensors, GMR sensors are cheaper, more
      sensitive, can generate fully electronic signals, and can be easily integrated
      with electronics and microfluidics. The GMR sensor used in this work has a bottom
      spin valve structure with an MR ratio of 12%. The single-strand target DNA
      detected has a length of 20 bases. Assays with DNA concentrations down to 10 pM
      were performed, with a dynamic range of 3 logs. A double modulation technique was
      used in signal detection to reduce the 1/f noise in the sensor while
      circumventing electromagnetic interference. The logarithmic relationship between
      the magnetic signal and the target DNA concentration can be described by the
      Temkin isotherm. Furthermore, GMR sensors integrated with microfluidics has great
      potential of improving the sensitivity to 1 pM or below, and the total assay time
      can be reduced to less than 1 hour.

PMID- 20824117
TI  - Collaborative Implementation of a Sequenced Trauma-Focused Intervention for Youth
      in Residential Care.
AB  - Few evidence-based interventions have been developed or tested with youth in
      residential care. Moreover, models for transferring implementation knowledge from
      clinical trials to service settings are sparse. This paper addresses the lessons
      learned about addressing this technology transfer gap by presenting a case study
      of a collaborative effort to implement a trauma-informed pilot program with youth
      in residential care. Key considerations are the collaborative nature of
      implementation efforts, the requirement of organizational support, the need for
      interventions to be sensitive to the child and the milieu, and the lack of fit
      between Medicaid reimbursement and evidence-based intervention.

PMID- 20824118
TI  - Validation of Different Systems for Tumstatin Expression and its in-vitro and iv
      vivo Activities.
AB  - The aim of the present study is to identify an effective and efficient expression
      system for purification of recombinant antiangiogenic protein tumstatin. The
      sequence encoding carboxy-terminal non-collagenous domain of alpha3 chain Type IV
      collagen, alpha3(IV)NC1 (tumstatin) was isolated from human placental tissue and
      cloned in three different expression vectors pET22b, pcBFT and pAcHLT-A to
      express it in bacteria, mammalian and Sf-9 insect cells respectively. Expression
      and purification profiles of tumstatin were evaluated by coomassie staining and
      immunoblotting, and the efficiency was determined based on the yields of soluble
      protein. Our results indicate that, baculovirus expression system was efficient
      for scalable yields of soluble protein that could be purified in its biologically
      active form. This baculovirus expressed tumstatin was used to evaluate its anti
      angiogenic and anti-tumarogenic functions such as inhibition of endothelial cell
      proliferation, cell viability, migration, tube formation, cap dependent protein
      translation and the associated signaling mechanism including in-vivo tumor study.
      Our evaluated approaches using a modified baculovirus expression system shows
      high expression and high yield of biologically active tumstatin, as compared to
      two expression systems, indicating baculovirus expression system to be an ideal
      method for bulk production of soluble tumstatin that needed for pre-clinical and
      clinical trails.

PMID- 20824119
TI  - Comparison of scales to evaluate the progression of HIV-associated neurocognitive
      disorder.
AB  - AIM: First, to compare the characterization of neurocognitive deficits in milder
      stages of HIV-associated neurocognitive disorder (HAND) derived from existing
      dementia rating scales of the American Academy of Neurology (AAN) and Memorial
      Sloan Kettering (MSK) with the 2007 consensus ('Frascati') classification.
      Second, to identify potential sociodemographic and clinical predictors of HAND
      progression during 1-year follow-up. METHODS: 104 HIV-infected subjects in an
      existing cohort system were evaluated with a medical history, exam,
      neuropsychological test battery and functional assessments. The degree of HAND
      was rated using the AAN, MSK and Frascati scales. The degree of concordance among
      these scales was determined. In addition, 45 subjects were reassessed for changes
      in their neurocognitive status at 1-year follow-up. Associations between age,
      education, sex, depression ratings, substance abuse, race, hepatitis C
      serostatus, CD4 count and progression of HAND were examined. RESULTS: There was
      excellent concordance (gamma > 0.8) among the Frascati, MSK and AAN ratings.
      Subjects rated as having minor cognitive motor disorder on the AAN scale (n = 45)
      were evenly split between Frascati rating of asymptomatic neurocognitive
      impairment (n = 24) and mild neurocognitive disorder (n = 21). At 1-year follow
      up of 45 subjects, 31% had worsened, 13% had improved and 56% were stable.
      Predictors of progression included age older than 50 years (odds ratio: 5.57; p =
      0.013) and female gender (odds ratio: 3.13; p = 0.036). CONCLUSION: The Frascati
      HAND rating scale has excellent concordance with previous neurocognitive rating
      scales and can be used to better characterize milder stages of cognitive
      impairment. Older individuals and women appeared to be more likely to show
      neurocognitive progression.

PMID- 20824120
TI  - Immunocytochemical studies of aquaporin 4, Kir4.1, and alpha1-syntrophin in the
      astrocyte endfeet of mouse brain capillaries.
AB  - One of the most important physiological roles of brain astrocytes is the
      maintenance of extracellular K(+) concentration by adjusting the K(+) influx and
      K(+) efflux. The inwardly rectifying K(+) channel Kir4.1 has been identified as
      an important member of K(+) channels and is highly concentrated in glial endfeet
      membranes. Aquaporin (AQP) 4 is another abundantly expressed molecule in
      astrocyte endfeet membranes. We examined the ultrastructural localization of
      Kir4.1, AQP4, alpha1-syntrophin, and beta-spectrin molecules to understand the
      functional role(s) of Kir4.1 and AQP4. Immunogold electron microscopy of these
      molecules showed that the signals of these molecules were present along the
      plasma membranes of astrocyte endfeet. Double immunogold electron microscopy
      showed frequent co-localization in the combination of molecules of Kir4.1 and
      AQP4, Kir4.1 and alpha1-syntrophin, and AQP4 and alpha1-syntrophin, but not those
      of AQP4 and beta-spectrin. Our results support biochemical evidence that both
      Kir4.1 and AQP4 are associated with alpha1-syntrophin by way of postsynaptic
      density-95, Drosophila disc large protein, and the Zona occludens protein I
      protein-interaction domain. Co-localization of AQP4 and Kir4.1 may indicate that
      water flux mediated by AQP4 is associated with K(+) siphoning.

PMID- 20824121
TI  - VAMP2 marks quiescent satellite cells and myotubes, but not activated myoblasts.
AB  - We examined the expression and intracellular localization of vesicle-associated
      membrane protein 2 (VAMP2) during the differentiation of skeletal muscle cells by
      immunofluorescence microscopy. In isolated single myofibers, VAMP2 was expressed
      in quiescent satellite cells, downregulated in proliferating myoblastic cells,
      and re-expressed with differentiation. In the myoblastic cell line C2C12, VAMP2
      was expressed at a low level in the proliferating stage, and then increased after
      differentiation into myotubes. Based on these results, we propose that VAMP2 can
      be used as a molecular marker for both quiescent satellite cells and myotubes,
      but not for proliferating myoblasts. We also found the partial colocalization of
      VAMP2 with transferrin- or Rab11-labeled vesicles in myotubes, suggesting a role
      of VAMP2 in the trafficking of recycling endosomes.

PMID- 20824122
TI  - Forcing versus feedback: epidemic malaria and monsoon rains in northwest India.
AB  - Malaria epidemics in regions with seasonal windows of transmission can vary
      greatly in size from year to year. A central question has been whether these
      interannual cycles are driven by climate, are instead generated by the intrinsic
      dynamics of the disease, or result from the resonance of these two mechanisms.
      This corresponds to the more general inverse problem of identifying the
      respective roles of external forcings vs. internal feedbacks from time series for
      nonlinear and noisy systems. We propose here a quantitative approach to formally
      compare rival hypotheses on climate vs. disease dynamics, or external forcings
      vs. internal feedbacks, that combines dynamical models with recently developed,
      computational inference methods. The interannual patterns of epidemic malaria are
      investigated here for desert regions of northwest India, with extensive
      epidemiological records for Plasmodium falciparum malaria for the past two
      decades. We formulate a dynamical model of malaria transmission that explicitly
      incorporates rainfall, and we rely on recent advances on parameter estimation for
      nonlinear and stochastic dynamical systems based on sequential Monte Carlo
      methods. Results show a significant effect of rainfall in the inter-annual
      variability of epidemic malaria that involves a threshold in the disease
      response. The model exhibits high prediction skill for yearly cases in the
      malaria transmission season following the monsoonal rains. Consideration of a
      more complex model with clinical immunity demonstrates the robustness of the
      findings and suggests a role of infected individuals that lack clinical symptoms
      as a reservoir for transmission. Our results indicate that the nonlinear dynamics
      of the disease itself play a role at the seasonal, but not the interannual, time
      scales. They illustrate the feasibility of forecasting malaria epidemics in
      desert and semi-arid regions of India based on climate variability. This approach
      should be applicable to malaria in other locations, to other infectious diseases,
      and to other nonlinear systems under forcing.

PMID- 20824123
TI  - Regression analysis for constraining free parameters in electrophysiological
      models of cardiac cells.
AB  - A major challenge in computational biology is constraining free parameters in
      mathematical models. Adjusting a parameter to make a given model output more
      realistic sometimes has unexpected and undesirable effects on other model
      behaviors. Here, we extend a regression-based method for parameter sensitivity
      analysis and show that a straightforward procedure can uniquely define most ionic
      conductances in a well-known model of the human ventricular myocyte. The model's
      parameter sensitivity was analyzed by randomizing ionic conductances, running
      repeated simulations to measure physiological outputs, then collecting the
      randomized parameters and simulation results as "input" and "output" matrices,
      respectively. Multivariable regression derived a matrix whose elements indicate
      how changes in conductances influence model outputs. We show here that if the
      number of linearly-independent outputs equals the number of inputs, the
      regression matrix can be inverted. This is significant, because it implies that
      the inverted matrix can specify the ionic conductances that are required to
      generate a particular combination of model outputs. Applying this idea to the
      myocyte model tested, we found that most ionic conductances could be specified
      with precision (R(2) > 0.77 for 12 out of 16 parameters). We also applied this
      method to a test case of changes in electrophysiology caused by heart failure and
      found that changes in most parameters could be well predicted. We complemented
      our findings using a Bayesian approach to demonstrate that model parameters
      cannot be specified using limited outputs, but they can be successfully
      constrained if multiple outputs are considered. Our results place on a solid
      mathematical footing the intuition-based procedure simultaneously matching a
      model's output to several data sets. More generally, this method shows promise as
      a tool to define model parameters, in electrophysiology and in other biological
      fields.

PMID- 20824124
TI  - Diversity and plasticity of Th cell types predicted from regulatory network
      modelling.
AB  - Alternative cell differentiation pathways are believed to arise from the
      concerted action of signalling pathways and transcriptional regulatory networks.
      However, the prediction of mammalian cell differentiation from the knowledge of
      the presence of specific signals and transcriptional factors is still a daunting
      challenge. In this respect, the vertebrate hematopoietic system, with its many
      branching differentiation pathways and cell types, is a compelling case study. In
      this paper, we propose an integrated, comprehensive model of the regulatory
      network and signalling pathways controlling Th cell differentiation. As most
      available data are qualitative, we rely on a logical formalism to perform
      extensive dynamical analyses. To cope with the size and complexity of the
      resulting network, we use an original model reduction approach together with a
      stable state identification algorithm. To assess the effects of heterogeneous
      environments on Th cell differentiation, we have performed a systematic series of
      simulations considering various prototypic environments. Consequently, we have
      identified stable states corresponding to canonical Th1, Th2, Th17 and Treg
      subtypes, but these were found to coexist with other transient hybrid cell types
      that co-express combinations of Th1, Th2, Treg and Th17 markers in an environment
      dependent fashion. In the process, our logical analysis highlights the nature of
      these cell types and their relationships with canonical Th subtypes. Finally, our
      logical model can be used to explore novel differentiation pathways in silico.

PMID- 20824125
TI  - Occurrence and treatment of bone atrophic non-unions investigated by an
      integrative approach.
AB  - Recently developed atrophic non-union models are a good representation of the
      clinical situation in which many non-unions develop. Based on previous
      experimental studies with these atrophic non-union models, it was hypothesized
      that in order to obtain successful fracture healing, blood vessels, growth
      factors, and (proliferative) precursor cells all need to be present in the callus
      at the same time. This study uses a combined in vivo-in silico approach to
      investigate these different aspects (vasculature, growth factors, cell
      proliferation). The mathematical model, initially developed for the study of
      normal fracture healing, is able to capture essential aspects of the in vivo
      atrophic non-union model despite a number of deviations that are mainly due to
      simplifications in the in silico model. The mathematical model is subsequently
      used to test possible treatment strategies for atrophic non-unions (i.e. cell
      transplant at post-osteotomy, week 3). Preliminary in vivo experiments
      corroborate the numerical predictions. Finally, the mathematical model is applied
      to explain experimental observations and identify potentially crucial steps in
      the treatments and can thereby be used to optimize experimental and clinical
      studies in this area. This study demonstrates the potential of the combined in
      silico-in vivo approach and its clinical implications for the early treatment of
      patients with problematic fractures.

PMID- 20824126
TI  - Current estimates for HIV-1 production imply rapid viral clearance in lymphoid
      tissues.
AB  - It has recently been estimated that a single HIV-1 infected cell produces between
      and more than viral particles over its life span. Since body-wide estimates of
      the ratio of free virus to productively infected cells are smaller than and much
      smaller than , individual virions must be cleared rapidly. This seems difficult
      to reconcile with the fact that most of the total body virus is trapped on
      follicular dendritic cells where it can survive for many months. It has also been
      difficult to reconcile the vast difference in the rates at which the virus is
      cleared from the blood in rhesus macaques and in chronically infected patients.
      Here we attempt to reconcile these seemingly contradictory observations by
      considering the virion clearance rate in various organs and the virion exchange
      rates between them. The main results are that the per capita clearance rate of
      free virus in lymphoid tissue should be fast, the virion exchange rate between
      lymphoid tissue and the blood should be slow, and the comparatively slow previous
      estimates for the virion clearance rate from the blood correspond to the rate of
      virion efflux from the blood to other organs where the virus is ultimately
      cleared.

PMID- 20824127
TI  - Differences in nutrient requirements imply a non-linear emergence of leaders in
      animal groups.
AB  - Collective decision making and especially leadership in groups are among the most
      studied topics in natural, social, and political sciences. Previous studies have
      shown that some individuals are more likely to be leaders because of their social
      power or the pertinent information they possess. One challenge for all group
      members, however, is to satisfy their needs. In many situations, we do not yet
      know how individuals within groups distribute leadership decisions between
      themselves in order to satisfy time-varying individual requirements. To gain
      insight into this problem, we build a dynamic model where group members have to
      satisfy different needs but are not aware of each other's needs. Data about needs
      of animals come from real data observed in macaques. Several studies showed that
      a collective movement may be initiated by a single individual. This individual
      may be the dominant one, the oldest one, but also the one having the highest
      physiological needs. In our model, the individual with the lowest reserve
      initiates movements and decides for all its conspecifics. This simple rule leads
      to a viable decision-making system where all individuals may lead the group at
      one moment and thus suit their requirements. However, a single individual becomes
      the leader in 38% to 95% of cases and the leadership is unequally (according to
      an exponential law) distributed according to the heterogeneity of needs in the
      group. The results showed that this non-linearity emerges when one group member
      reaches physiological requirements, mainly the nutrient ones - protein, energy
      and water depending on weight - superior to those of its conspecifics. This
      amplification may explain why some leaders could appear in animal groups without
      any despotism, complex signalling, or developed cognitive ability.

PMID- 20824128
TI  - Latent factor analysis to discover pathway-associated putative segmental
      aneuploidies in human cancers.
AB  - Tumor microenvironmental stresses, such as hypoxia and lactic acidosis, play
      important roles in tumor progression. Although gene signatures reflecting the
      influence of these stresses are powerful approaches to link expression with
      phenotypes, they do not fully reflect the complexity of human cancers. Here, we
      describe the use of latent factor models to further dissect the stress gene
      signatures in a breast cancer expression dataset. The genes in these latent
      factors are coordinately expressed in tumors and depict distinct, interacting
      components of the biological processes. The genes in several latent factors are
      highly enriched in chromosomal locations. When these factors are analyzed in
      independent datasets with gene expression and array CGH data, the expression
      values of these factors are highly correlated with copy number alterations (CNAs)
      of the corresponding BAC clones in both the cell lines and tumors. Therefore,
      variation in the expression of these pathway-associated factors is at least
      partially caused by variation in gene dosage and CNAs among breast cancers. We
      have also found the expression of two latent factors without any chromosomal
      enrichment is highly associated with 12q CNA, likely an instance of "trans"
      variations in which CNA leads to the variations in gene expression outside of the
      CNA region. In addition, we have found that factor 26 (1q CNA) is negatively
      correlated with HIF-1alpha protein and hypoxia pathways in breast tumors and cell
      lines. This agrees with, and for the first time links, known good prognosis
      associated with both a low hypoxia signature and the presence of CNA in this
      region. Taken together, these results suggest the possibility that tumor
      segmental aneuploidy makes significant contributions to variation in the lactic
      acidosis/hypoxia gene signatures in human cancers and demonstrate that latent
      factor analysis is a powerful means to uncover such a linkage.

PMID- 20824129
TI  - Allelic selection of amplicons in glioblastoma revealed by combining somatic and
      germline analysis.
AB  - Cancer is a disease driven by a combination of inherited risk alleles coupled
      with the acquisition of somatic mutations, including amplification and deletion
      of genomic DNA. Potential relationships between the inherited and somatic aspects
      of the disease have only rarely been examined on a genome-wide level. Applying a
      novel integrative analysis of SNP and copy number measurements, we queried the
      tumor and normal-tissue genomes of 178 glioblastoma patients from the Cancer
      Genome Atlas project for preferentially amplified alleles, under the hypothesis
      that oncogenic germline variants will be selectively amplified in the tumor
      environment. Selected alleles are revealed by allelic imbalance in amplification
      across samples. This general approach is based on genetic principles and provides
      a method for identifying important tumor-related alleles. We find that SNP
      alleles that are most significantly overrepresented in amplicons tend to occur in
      genes involved with regulation of kinase and transferase activity, and many of
      these genes are known contributors to gliomagenesis. The analysis also implicates
      variants in synapse genes. By incorporating gene expression data, we demonstrate
      synergy between preferential allelic amplification and expression in DOCK4 and
      EGFR. Our results support the notion that combining germline and tumor genetic
      data can identify regions relevant to cancer biology.

PMID- 20824130
TI  - Inhibition of GSK-3 ameliorates Abeta pathology in an adult-onset Drosophila
      model of Alzheimer's disease.
AB  - Abeta peptide accumulation is thought to be the primary event in the pathogenesis
      of Alzheimer's disease (AD), with downstream neurotoxic effects including the
      hyperphosphorylation of tau protein. Glycogen synthase kinase-3 (GSK-3) is
      increasingly implicated as playing a pivotal role in this amyloid cascade. We
      have developed an adult-onset Drosophila model of AD, using an inducible gene
      expression system to express Arctic mutant Abeta42 specifically in adult neurons,
      to avoid developmental effects. Abeta42 accumulated with age in these flies and
      they displayed increased mortality together with progressive neuronal
      dysfunction, but in the apparent absence of neuronal loss. This fly model can
      thus be used to examine the role of events during adulthood and early AD
      aetiology. Expression of Abeta42 in adult neurons increased GSK-3 activity, and
      inhibition of GSK-3 (either genetically or pharmacologically by lithium
      treatment) rescued Abeta42 toxicity. Abeta42 pathogenesis was also reduced by
      removal of endogenous fly tau; but, within the limits of detection of available
      methods, tau phosphorylation did not appear to be altered in flies expressing
      Abeta42. The GSK-3-mediated effects on Abeta42 toxicity appear to be at least in
      part mediated by tau-independent mechanisms, because the protective effect of
      lithium alone was greater than that of the removal of tau alone. Finally, Abeta42
      levels were reduced upon GSK-3 inhibition, pointing to a direct role of GSK-3 in
      the regulation of Abeta42 peptide level, in the absence of APP processing. Our
      study points to the need both to identify the mechanisms by which GSK-3 modulates
      Abeta42 levels in the fly and to determine if similar mechanisms are present in
      mammals, and it supports the potential therapeutic use of GSK-3 inhibitors in AD.

PMID- 20824131
TI  - Prediction of nucleosome positioning based on transcription factor binding sites.
AB  - BACKGROUND: The DNA of all eukaryotic organisms is packaged into nucleosomes, the
      basic repeating units of chromatin. The nucleosome consists of a histone octamer
      around which a DNA core is wrapped and the linker histone H1, which is associated
      with linker DNA. By altering the accessibility of DNA sequences, the nucleosome
      has profound effects on all DNA-dependent processes. Understanding the factors
      that influence nucleosome positioning is of great importance for the study of
      genomic control mechanisms. Transcription factors (TFs) have been suggested to
      play a role in nucleosome positioning in vivo. PRINCIPAL FINDINGS: Here, the
      minimum redundancy maximum relevance (mRMR) feature selection algorithm, the
      nearest neighbor algorithm (NNA), and the incremental feature selection (IFS)
      method were used to identify the most important TFs that either favor or inhibit
      nucleosome positioning by analyzing the numbers of transcription factor binding
      sites (TFBSs) in 53,021 nucleosomal DNA sequences and 50,299 linker DNA
      sequences. A total of nine important families of TFs were extracted from 35
      families, and the overall prediction accuracy was 87.4% as evaluated by the
      jackknife cross-validation test. CONCLUSIONS: Our results are consistent with the
      notion that TFs are more likely to bind linker DNA sequences than the sequences
      in the nucleosomes. In addition, our results imply that there may be some TFs
      that are important for nucleosome positioning but that play an insignificant role
      in discriminating nucleosome-forming DNA sequences from nucleosome-inhibiting DNA
      sequences. The hypothesis that TFs play a role in nucleosome positioning is,
      thus, confirmed by the results of this study.

PMID- 20824132
TI  - An updated meta-analysis of risk of multiple sclerosis following infectious
      mononucleosis.
AB  - BACKGROUND: Multiple sclerosis (MS) appears to develop in genetically susceptible
      individuals as a result of environmental exposures. Epstein-Barr virus (EBV)
      infection is an almost universal finding among individuals with MS. Symptomatic
      EBV infection as manifested by infectious mononucleosis (IM) has been shown in a
      previous meta-analysis to be associated with the risk of MS, however a number of
      much larger studies have since been published. METHODS/PRINCIPAL FINDINGS: We
      performed a Medline search to identify articles published since the original meta
      analysis investigating MS risk following IM. A total of 18 articles were included
      in this study, including 19390 MS patients and 16007 controls. We calculated the
      relative risk of MS following IM using a generic inverse variance with random
      effects model. This showed that the risk of MS was strongly associated with IM
      (relative risk (RR) 2.17; 95% confidence interval 1.97-2.39; p<10(-54)).
      DISCUSSION: Our results establish firmly that a history of infectious
      mononucleosis significantly increases the risk of multiple sclerosis. Future work
      should focus on the mechanism of this association and interaction with other risk
      factors.

PMID- 20824133
TI  - Prediction and testing of biological networks underlying intestinal cancer.
AB  - Colorectal cancer progresses through an accumulation of somatic mutations, some
      of which reside in so-called "driver" genes that provide a growth advantage to
      the tumor. To identify points of intersection between driver gene pathways, we
      implemented a network analysis framework using protein interactions to predict
      likely connections--both precedented and novel--between key driver genes in
      cancer. We applied the framework to find significant connections between two
      genes, Apc and Cdkn1a (p21), known to be synergistic in tumorigenesis in mouse
      models. We then assessed the functional coherence of the resulting Apc-Cdkn1a
      network by engineering in vivo single node perturbations of the network: mouse
      models mutated individually at Apc (Apc(1638N+/-)) or Cdkn1a (Cdkn1a(-/-)),
      followed by measurements of protein and gene expression changes in intestinal
      epithelial tissue. We hypothesized that if the predicted network is biologically
      coherent (functional), then the predicted nodes should associate more
      specifically with dysregulated genes and proteins than stochastically selected
      genes and proteins. The predicted Apc-Cdkn1a network was significantly perturbed
      at the mRNA-level by both single gene knockouts, and the predictions were also
      strongly supported based on physical proximity and mRNA coexpression of proteomic
      targets. These results support the functional coherence of the proposed Apc
      Cdkn1a network and also demonstrate how network-based predictions can be
      statistically tested using high-throughput biological data.

PMID- 20824134
TI  - Telomerase inhibition targets clonogenic multiple myeloma cells through telomere
      length-dependent and independent mechanisms.
AB  - BACKGROUND: Plasma cells constitute the majority of tumor cells in multiple
      myeloma (MM) but lack the potential for sustained clonogenic growth. In contrast,
      clonotypic B cells can engraft and recapitulate disease in immunodeficient mice
      suggesting they serve as the MM cancer stem cell (CSC). These tumor initiating B
      cells also share functional features with normal stem cells such as drug
      resistance and self-renewal potential. Therefore, the cellular processes that
      regulate normal stem cells may serve as therapeutic targets in MM. Telomerase
      activity is required for the maintenance of normal adult stem cells, and we
      examined the activity of the telomerase inhibitor imetelstat against MM CSC.
      Moreover, we carried out both long and short-term inhibition studies to examine
      telomere length-dependent and independent activities. METHODOLOGY/PRINCIPAL
      FINDINGS: Human MM CSC were isolated from cell lines and primary clinical
      specimens and treated with imetelstat, a specific inhibitor of the reverse
      transcriptase activity of telomerase. Two weeks of exposure to imetelstat
      resulted in a significant reduction in telomere length and the inhibition of
      clonogenic MM growth both in vitro and in vivo. In addition to these relatively
      long-term effects, 72 hours of imetelstat treatment inhibited clonogenic growth
      that was associated with MM CSC differentiation based on expression of the plasma
      cell antigen CD138 and the stem cell marker aldehyde dehydrogenase. Short-term
      treatment of MM CSC also decreased the expression of genes typically expressed by
      stem cells (OCT3/4, SOX2, NANOG, and BMI1) as revealed by quantitative real-time
      PCR. CONCLUSIONS: Telomerase activity regulates the clonogenic growth of MM CSC.
      Moreover, reductions in MM growth following both long and short-term telomerase
      inhibition suggest that it impacts CSC through telomere length-dependent and
      independent mechanisms.

PMID- 20824135
TI  - The effects of aging on the molecular and cellular composition of the prostate
      microenvironment.
AB  - BACKGROUND: Advancing age is associated with substantial increases in the
      incidence rates of common diseases affecting the prostate gland including benign
      prostatic hyperplasia (BPH) and prostate carcinoma. The prostate is comprised of
      a functional secretory epithelium, a basal epithelium, and a supporting stroma
      comprised of structural elements, and a spectrum of cell types that includes
      smooth muscle cells, fibroblasts, and inflammatory cells. As reciprocal
      interactions between epithelium and stromal constituents are essential for normal
      organogenesis and serve to maintain normal functions, discordance within the
      stroma could permit or promote disease processes. In this study we sought to
      identify aging-associated alterations in the mouse prostate microenvironment that
      could influence pathology. METHODOLOGY/PRINCIPAL FINDINGS: We quantitated
      transcript levels in microdissected glandular-adjacent stroma from young (age 4
      months) and old (age 20-24 months) C57BL/6 mice, and identified a significant
      change in the expression of 1259 genes (p<0.05). These included increases in
      transcripts encoding proteins associated with inflammation (e.g., Ccl8, Ccl12),
      genotoxic/oxidative stress (e.g., Apod, Serpinb5) and other paracrine-acting
      effects (e.g., Cyr61). The expression of several collagen genes (e.g., Col1a1 and
      Col3a1) exhibited age-associated declines. By histology, immunofluorescence, and
      electron microscopy we determined that the collagen matrix is abundant and
      disorganized, smooth muscle cell orientation is disordered, and inflammatory
      infiltrates are significantly increased, and are comprised of macrophages, T
      cells and, to a lesser extent, B cells. CONCLUSION/SIGNIFICANCE: These findings
      demonstrate that during normal aging the prostate stroma exhibits phenotypic and
      molecular characteristics plausibly contributing to the striking age associated
      pathologies affecting the prostate.

PMID- 20824136
TI  - Decay kinetics of an interferon gamma release assay with anti-tuberculosis
      therapy in newly diagnosed tuberculosis cases.
AB  - BACKGROUND: Qualitative and quantitative changes in IGRA response offer promise
      as biomarkers to monitor Tuberculosis (TB) drug therapy, and for the comparison
      of new interventions. We studied the decay kinetics of TB-specific antigen T-cell
      responses measured with an in-house ELISPOT assay during the course of therapy.
      METHODS: Newly diagnosed sputum smear positive TB cases with typical TB chest
      radiographs were recruited. All patients were given standard anti-TB treatment.
      Each subject was followed up for 6 months and treatment outcomes were documented.
      Blood samples were obtained for the ESAT-6 and CFP-10 (EC) ELISPOT at diagnosis,
      1-, 2-, 4- and 6-months. Qualitative and quantitative reversion of the ELISPOT
      results were assessed with McNemar test, conditional logistic regression and
      mixed-effects hierarchical Poisson models. RESULTS: A total of 116 cases were
      recruited and EC ELISPOT was positive for 87% (95 of 109) at recruitment. There
      was a significant decrease in the proportion of EC ELISPOT positive cases over
      the treatment period (p<0.001). Most of the reversion occurred between the start
      and first month of treatment and at completion at 6 months. ESAT-6 had higher
      median counts compared to CFP-10 at all time points. Counts for each antigen
      declined significantly with therapy (p<0.001). Reverters had lower median SFUs at
      the start of treatment compared to non-Reverters for both antigens. Apart from
      the higher median counts for non-Reverters, no other risk factors for non
      reversion were found. CONCLUSIONS: TB treatment induces qualitative and
      quantitative reversion of a positive in-house IGRA in newly diagnosed cases of
      active TB disease. As this does not occur reliably in the majority of cured
      individuals, qualitative and quantitative reversion of an IGRA ELISPOT has
      limited clinical utility as a surrogate marker of treatment efficacy.

PMID- 20824137
TI  - Attentional prioritization of infant faces is limited to own-race infants.
AB  - BACKGROUND: Recent evidence indicates that infant faces capture attention
      automatically, presumably to elicit caregiving behavior from adults and leading
      to greater probability of progeny survival. Elsewhere, evidence demonstrates that
      people show deficiencies in the processing of other-race relative to own-race
      faces. We ask whether this other-race effect impacts on attentional attraction to
      infant faces. Using a dot-probe task to reveal the spatial allocation of
      attention, we investigate whether other-race infants capture attention. PRINCIPAL
      FINDINGS: South Asian and White participants (young adults aged 18-23 years)
      responded to a probe shape appearing in a location previously occupied by either
      an infant face or an adult face; across trials, the race (South Asian/White) of
      the faces was manipulated. Results indicated that participants were faster to
      respond to probes that appeared in the same location as infant faces than adult
      faces, but only on own-race trials. CONCLUSIONS/SIGNIFICANCE: Own-race infant
      faces attract attention, but other-race infant faces do not. Sensitivity to face
      specific care-seeking cues in other-race kindenschema may be constrained by
      interracial contact and experience.

PMID- 20824138
TI  - Gene knock-outs of inositol 1,4,5-trisphosphate receptors types 1 and 2 result in
      perturbation of cardiogenesis.
AB  - BACKGROUND: Inositol 1,4,5-trisphosphate receptors (IP3R1, 2, and 3) are
      intracellular Ca2+ release channels that regulate various vital processes.
      Although the ryanodine receptor type 2, another type of intracellular Ca2+
      release channel, has been shown to play a role in embryonic cardiomyocytes, the
      functions of the IP3Rs in cardiogenesis remain unclear. METHODOLOGY/PRINCIPAL
      FINDINGS: We found that IP3R1(-/-)-IP3R2(-/-) double-mutant mice died in utero
      with developmental defects of the ventricular myocardium and atrioventricular
      (AV) canal of the heart by embryonic day (E) 11.5, even though no cardiac defect
      was detectable in IP3R1(-/-) or IP3R2(-/-) single-mutant mice at this
      developmental stage. The double-mutant phenotype resembled that of mice deficient
      for calcineurin/NFATc signaling, and NFATc was inactive in embryonic hearts from
      the double knockout-mutant mice. The double mutation of IP3R1/R2 and
      pharmacologic inhibition of IP3Rs mimicked the phenotype of the AV valve defect
      that result from the inhibition of calcineurin, and it could be rescued by
      constitutively active calcineurin. CONCLUSIONS/SIGNIFICANCE: Our results suggest
      an essential role for IP3Rs in cardiogenesis in part through the regulation of
      calcineurin-NFAT signaling.

PMID- 20824139
TI  - Broad spectrum antiangiogenic treatment for ocular neovascular diseases.
AB  - Pathological neovascularization is a hallmark of late stage neovascular (wet) age
      related macular degeneration (AMD) and the leading cause of blindness in people
      over the age of 50 in the western world. The treatments focus on suppression of
      choroidal neovascularization (CNV), while current approved therapies are limited
      to inhibiting vascular endothelial growth factor (VEGF) exclusively. However,
      this treatment does not address the underlying cause of AMD, and the loss of
      VEGF's neuroprotective can be a potential side effect. Therapy which targets the
      key processes in AMD, the pathological neovascularization, vessel leakage and
      inflammation could bring a major shift in the approach to disease treatment and
      prevention. In this study we have demonstrated the efficacy of such broad
      spectrum antiangiogenic therapy on mouse model of AMD. METHODS AND FINDINGS:
      Lodamin, a polymeric formulation of TNP-470, is a potent broad-spectrum
      antiangiogenic drug. Lodamin significantly reduced key processes involved in AMD
      progression as demonstrated in mice and rats. Its suppressive effects on
      angiogenesis, vascular leakage and inflammation were studied in a wide array of
      assays including; a Matrigel, delayed-type hypersensitivity (DTH), Miles assay,
      laser-induced CNV and corneal micropocket assay. Lodamin significantly suppressed
      the secretion of various pro-inflammatory cytokines in the CNV lesion including
      monocyte chemotactic protein-1 (MCP-1/Ccl2). Importantly, Lodamin was found to
      regress established CNV lesions, unlike soluble fms-like tyrosine kinase-1 (sFlk
      1). The drug was found to be safe in mice and have little toxicity as
      demonstrated by electroretinography (ERG) assessing retinal and by histology.
      CONCLUSIONS: Lodamin, a polymer formulation of TNP-470, was identified as a first
      in its class, broad-spectrum antiangiogenic drug that can be administered orally
      or locally to treat corneal and retinal neovascularization. Several unique
      properties make Lodamin especially beneficial for ophthalmic use. Our results
      support the concept that broad spectrum antiangiogenic drugs are promising agents
      for AMD treatment and prevention.

PMID- 20824140
TI  - MiRNA profile associated with replicative senescence, extended cell culture, and
      ectopic telomerase expression in human foreskin fibroblasts.
AB  - Senescence is a highly regulated process that limits cellular replication by
      enforcing a G1 arrest in response to various stimuli. Replicative senescence
      occurs in response to telomeric DNA erosion, and telomerase expression can offset
      replicative senescence leading to immortalization of many human cells. Limited
      data exists regarding changes of microRNA (miRNA) expression during senescence in
      human cells and no reports correlate telomerase expression with regulation of
      senescence-related miRNAs. We used miRNA microarrays to provide a detailed
      account of miRNA profiles for early passage and senescent human foreskin (BJ)
      fibroblasts as well as early and late passage immortalized fibroblasts (BJ-hTERT)
      that stably express the human telomerase reverse transcriptase subunit hTERT.
      Selected miRNAs that were differentially expressed in senescence were assayed for
      expression in quiescent cells to identify miRNAs that are specifically associated
      with senescence-associated growth arrest. From this group of senescence
      associated miRNAs, we confirmed the ability of miR-143 to induce growth arrest
      after ectopic expression in young fibroblasts. Remarkably, miR-143 failed to
      induce growth arrest in BJ-hTERT cells. Importantly, the comparison of late
      passage immortalized fibroblasts to senescent wild type fibroblasts reveals that
      miR-146a, a miRNA with a validated role in regulating the senescence associated
      secretory pathway, is also regulated during extended cell culture independently
      of senescence. The discovery that miRNA expression is impacted by expression of
      ectopic hTERT as well as extended passaging in immortalized fibroblasts
      contributes to a comprehensive understanding of the connections between
      telomerase expression, senescence and processes of cellular aging.

PMID- 20824141
TI  - Emergence of collective memories.
AB  - BACKGROUND: We understand the dynamics of the world around us as by associating
      pairs of events, where one event has some influence on the other. These pairs of
      events can be aggregated into a web of memories representing our understanding of
      an episode of history. The events and the associations between them need not be
      directly experienced-they can also be acquired by communication. In this paper we
      take a network approach to study the dynamics of memories of history.
      METHODOLOGY/PRINCIPAL FINDINGS: First we investigate the network structure of a
      data set consisting of reported events by several individuals and how
      associations connect them. We focus our measurement on degree distributions,
      degree correlations, cycles (which represent inconsistencies as they would break
      the time ordering) and community structure. We proceed to model effects of
      communication using an agent-based model. We investigate the conditions for the
      memory webs of different individuals to converge to collective memories, how
      groups where the individuals have similar memories (but different from other
      groups) can form. CONCLUSIONS/SIGNIFICANCE: Our work outlines how the cognitive
      representation of memories and social structure can co-evolve as a contagious
      process. We generate some testable hypotheses including that the number of groups
      is limited as a function of the total population size.

PMID- 20824142
TI  - Linking power Doppler ultrasound to the presence of th17 cells in the rheumatoid
      arthritis joint.
AB  - BACKGROUND: Power Doppler ultrasound (PDUS) is increasingly used to assess
      synovitis in Rheumatoid Arthritis (RA). Prior studies have shown correlations
      between PDUS scores and vessel counts, but relationships with T cell
      immunopathology have not been described. METHODOLOGY/PRINCIPAL FINDINGS: PBMC
      were isolated from healthy controls (HC) or RA patients and stimulated ex vivo
      with PMA and ionomycin for 3 hours in the presence of Golgistop. Paired synovial
      fluid (SF) or synovial tissue (ST) were analysed where available. Intracellular
      expression of IL-17, IFNgamma, and TNFalpha by CD4+ T cells was determined by
      flow cytometry. Synovial blood flow was evaluated by PDUS signal at the knees,
      wrists and metacarpophalangeal joints of RA patients. Serum, SF and fibroblast
      culture supernatant levels of vascular endothelial growth factor-A (VEGF-A) were
      measured by ELISA. The frequency of IL17+IFNgamma-CD4+ T cells (Th17 cells) was
      significantly elevated in peripheral blood (PB) from RA patients vs. HC (median
      (IQR) 0.5 (0.28-1.59)% vs. 0.32 (0.21-0.54)%, p = 0.005). Th17 cells were further
      enriched (mean 6.6-fold increase) in RA SF relative to RA PB. Patients with
      active disease had a higher percentage of IL-17+ T cells in ST than patients in
      remission, suggesting a possible role for Th17 cells in active synovitis in RA.
      Indeed, the percentage of Th17 cells, but not Th1, in SF positively correlated
      with CRP (r = 0.51, p = 0.04) and local PDUS-defined synovitis (r = 0.61, p =
      0.002). Furthermore, patients with high levels of IL-17+CD4+ T cells in SF had
      increased levels of the angiogenic factor VEGF-A in SF. Finally, IL-17, but not
      IFNgamma, increased VEGF-A production by RA synovial fibroblasts in vitro.
      CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a link between the presence of pro
      inflammatory Th17 cells in SF and local PDUS scores, and offer a novel
      immunological explanation for the observation that rapid joint damage progression
      occurs in patients with persistent positive PDUS signal.

PMID- 20824143
TI  - Preservation of differentiation and clonogenic potential of human hematopoietic
      stem and progenitor cells during lyophilization and ambient storage.
AB  - Progenitor cell therapies show great promise, but their potential for clinical
      applications requires improved storage and transportation. Desiccated cells
      stored at ambient temperature would provide economic and practical advantages
      over approaches employing cell freezing and subzero temperature storage. The
      objectives of this study were to assess a method for loading the stabilizing
      sugar, trehalose, into hematopoietic stem and progenitor cells (HPC) and to
      evaluate the effects of subsequent freeze-drying and storage at ambient
      temperature on differentiation and clonogenic potential. HPC were isolated from
      human umbilical cord blood and loaded with trehalose using an endogenous cell
      surface receptor, termed P2Z. Solution containing trehalose-loaded HPC was placed
      into vials, which were transferred to a tray freeze-dryer and removed during each
      step of the freeze-drying process to assess differentiation and clonogenic
      potential. Control groups for these experiments were freshly isolated HPC.
      Control cells formed 1450+/-230 CFU-GM, 430+/-140 BFU-E, and 50+/-40 CFU-GEMM per
      50 microL. Compared to the values for the control cells, there was no statistical
      difference observed for cells removed at the end of the freezing step or at the
      end of primary drying. There was a gradual decrease in the number of CFU-GM and
      BFU-E for cells removed at different temperatures during secondary drying;
      however, there were no significant differences in the number of CFU-GEMM. To
      determine storage stability of lyophilized HPC, cells were stored for 4 weeks at
      25 degrees C in the dark. Cells reconstituted immediately after lyophilization
      produced 580+/-90 CFU-GM ( approximately 40%, relative to unprocessed controls
      p<0.0001), 170+/-70 BFU-E (approximately 40%, p<0.0001), and 41+/-22 CFU-GEMM
      (approximately 82%, p = 0.4171), and cells reconstituted after 28 days at room
      temperature produced 513+/-170 CFU-GM (approximately 35%, relative to unprocessed
      controls, p<0.0001), 112+/-68 BFU-E (approximately 26%, p<0.0001), and 36+/-17
      CFU-GEMM ( approximately 82%, p = 0.2164) These studies are the first to document
      high level retention of CFU-GEMM following lyophilization and storage for 4 weeks
      at 25 degrees C. This type of flexible storage stability would potentially permit
      the ability to ship and store HPC without the need for refrigeration.

PMID- 20824144
TI  - alpha2,3-sialyltransferase ST3Gal III modulates pancreatic cancer cell motility
      and adhesion in vitro and enhances its metastatic potential in vivo.
AB  - BACKGROUND: Cell surface sialylation is emerging as an important feature of
      cancer cell metastasis. Sialyltransferase expression has been reported to be
      altered in tumours and may account for the formation of sialylated tumour
      antigens. We have focused on the influence of alpha-2,3-sialyltransferase ST3Gal
      III in key steps of the pancreatic tumorigenic process. METHODOLOGY/PRINCIPAL
      FINDINGS: ST3Gal III overexpressing pancreatic adenocarcinoma cell lines Capan-1
      and MDAPanc-28 were generated. They showed an increase of the tumour associated
      antigen sialyl-Lewis(x). The transfectants' E-selectin binding capacity was
      proportional to cell surface sialyl-Lewis(x) levels. Cellular migration
      positively correlated with ST3Gal III and sialyl-Lewis(x) levels. Moreover,
      intrasplenic injection of the ST3Gal III transfected cells into athymic nude mice
      showed a decrease in survival and higher metastasis formation when compared to
      the mock cells. CONCLUSION: In summary, the overexpression of ST3Gal III in these
      pancreatic adenocarcinoma cell lines underlines the role of this enzyme and its
      product in key steps of tumour progression such as adhesion, migration and
      metastasis formation.

PMID- 20824145
TI  - The neurokinin 1 receptor antagonist, ezlopitant, reduces appetitive responding
      for sucrose and ethanol.
AB  - BACKGROUND: The current obesity epidemic is thought to be partly driven by over
      consumption of sugar-sweetened diets and soft drinks. Loss-of-control over eating
      and addiction to drugs of abuse share overlapping brain mechanisms including
      changes in motivational drive, such that stimuli that are often no longer 'liked'
      are still intensely 'wanted' [7], . The neurokinin 1 (NK1) receptor system has
      been implicated in both learned appetitive behaviors and addiction to alcohol and
      opioids; however, its role in natural reward seeking remains unknown.
      METHODOLOGY/PRINCIPAL FINDINGS: We sought to determine whether the NK1-receptor
      system plays a role in the reinforcing properties of sucrose using a novel
      selective and clinically safe NK1-receptor antagonist, ezlopitant (CJ-11,974), in
      three animal models of sucrose consumption and seeking. Furthermore, we compared
      the effect of ezlopitant on ethanol consumption and seeking in rodents. The NK1
      receptor antagonist, ezlopitant decreased appetitive responding for sucrose more
      potently than for ethanol using an operant self-administration protocol without
      affecting general locomotor activity. To further evaluate the selectivity of the
      NK1-receptor antagonist in decreasing consumption of sweetened solutions, we
      compared the effects of ezlopitant on water, saccharin-, and sodium chloride
      (NaCl) solution consumption. Ezlopitant decreased intake of saccharin but had no
      effect on water or salty solution consumption. CONCLUSIONS/SIGNIFICANCE: The
      present study indicates that the NK1-receptor may be a part of a common pathway
      regulating the self-administration, motivational and reinforcing aspects of
      sweetened solutions, regardless of caloric value, and those of substances of
      abuse. Additionally, these results indicate that the NK1-receptor system may
      serve as a therapeutic target for obesity induced by over-consumption of natural
      reinforcers.

PMID- 20824147
TI  - SERIALITY AND SCIENTIFIC OBJECTS IN THE NINETEENTH CENTURY.

PMID- 20824146
TI  - Fifty-year fate and impact of general medical journals.
AB  - BACKGROUND: Influential medical journals shape medical science and practice and
      their prestige is usually appraised by citation impact metrics, such as the
      journal impact factor. However, how permanent are medical journals and how stable
      is their impact over time? METHODS AND RESULTS: We evaluated what happened to
      general medical journals that were publishing papers half a century ago, in 1959.
      Data were retrieved from ISI Web of Science for citations and PubMed (Journals
      function) for journal history. Of 27 eligible journals publishing in 1959, 4 have
      stopped circulation (including two of the most prestigious journals in 1959) and
      another 7 changed name between 1959 and 2009. Only 6 of these 27 journals have
      been published continuously with their initial name since they started
      circulation. The citation impact of papers published in 1959 gives a very
      different picture from the current journal impact factor; the correlation between
      the two is non-significant and very close to zero. Only 13 of the 5,223 papers
      published in 1959 received at least 5 citations in 2009. CONCLUSIONS: Journals
      are more permanent entities than single papers, but they are also subject to
      major change and their relative prominence can change markedly over time.

PMID- 20824148
TI  - Docking Small Molecules to Predicted Off-Targets of the Cancer Drug Erlotinib
      Leads to Inhibitors of Lung Cancer Cell Proliferation with Suitable In vitro
      Pharmacokinetic Properties.
AB  - In an effort to develop a rational approach to identify anti-cancer agents with
      selective polypharmacology, we mine millions of docked protein-ligand complexes
      involving more than a thousand cancer targets from multiple signaling pathways to
      identify new structural templates for proven pharmacophores. Our method combines
      Support Vector Machine-based scoring to enrich the initial library of 1,592
      molecules, with a fingerprint-based search for molecules that have the same
      binding profile as the EGFR kinase inhibitor erlotinib. Twelve new compounds were
      identified. In vitro activity assays revealed that three inhibited EGFR with
      IC(50) values ranging from 250 nM to 200 uM. Additional in vitro studies with
      hERG, CYP450, DNA and cell culture-based assays further compared their properties
      to erlotinib. One compound combined suitable pharmacokinetic properties while
      closely mimicking the binding profile of erlotinib. The compound also inhibited
      H1299 and H460 tumor cell proliferation. The other two compounds shared some of
      the binding profile of erlotinib, and one gave the most potent inhibition of
      tumor cell growth. Interestingly, among the compounds that had not shown
      inhibition of EGFR, four blocked H1299 and H460 proliferation, one potently with
      IC(50) values near 1 uM. This compound was from the menogaril family, which
      reached Phase II clinical trial for the treatment of lymphomas. This suggests
      that our computational approach comparing binding profile may have favored
      molecules with anti-cancer properties like erlotinib.

PMID- 20824149
TI  - Comparative Vision Science: Seeing Eye to Eye?
AB  - In the study of comparative cognition and perception, disparities in the diverse
      approaches that researchers take in studying behavior sometimes obscure the
      interpretation of a particular empirical finding. We describe an approach to the
      study of comparative cognition and perception which focuses on explaining the
      ways in which different biological systems solve the computational challenges
      that are posed by their natural environments. Within this investigative
      framework, the task of detecting correspondence between a three-dimensional
      object and its two-dimensional photographic representation falls outside the
      mainstream of most research in animal visual cognition and is of limited value
      for divulging the principles or mechanisms that underlie the visual abilities of
      animals. More productive pursuits seek to elucidate the principles and mechanisms
      of object recognition and categorization, and to illuminate how they contribute
      to the animal's survival in the visual world.

PMID- 20824150
TI  - Written Emotional Disclosure: Testing Whether Social Disclosure Matters.
AB  - Studies suggest that written emotional disclosure can improve health. Unknown,
      however, is whether the presence or absence of an audience for one's disclosure
      matters, and whether time management control writing has any effects.
      Undergraduates (N = 165) with unresolved stress were randomized to 1 of 3 groups
      that wrote for 4 sessions: shared written disclosure (submitted to researchers),
      private written disclosure (not submitted), or time management control writing;
      or to a fourth group (no-writing control). At 3-month follow-up, the two control
      groups were equivalent on outcomes. Both shared and private disclosure resulted
      in less cognitive intrusion and avoidance than the combined control groups. Yet,
      shared disclosure reduced depression and interpersonal sensitivity more than
      either private disclosure or the control groups, and only shared disclosure
      reduced physical symptoms. Although truly private writing improves cognitive
      stress effects, shared writing has broader benefits, suggesting that social
      disclosure for one's writing matters.

PMID- 20824152
TI  - Salvese Quien Pueda: Structural Adjustment and Emigration from Lima.
AB  - Beginning in 1987, Peru imposed a regime of structural adjustment to transform
      its economy along neoliberal lines. This analysis suggests that a shift resulted
      in the odds of international migration and the motivations for leaving among
      inhabitants of Peru's largest labor market. Before 1987, under the regime of
      import substitution industrialization, jobs at wages capable of sustaining a
      basic standard of living were widely available; those few who left the country
      self-selected for higher human capital and moved abroad to improve their
      earnings. Under neoliberalism, however, both employment and wages fell to levels
      that made it difficult for families to sustain themselves. In response,
      households-with the assistance of friends and relatives with foreign experience
      diversified their labor portfolios away from the local job market structural
      adjustment zones. The number of migrants then rose, the diversity of foreign
      destinations increased, and migration became less selective with respect to human
      capital.

PMID- 20824151
TI  - Treatment with pravastatin and fenofibrate improves atherogenic lipid profiles
      but not inflammatory markers in ACTG 5087.
AB  - OBJECTIVES: Statins and fibrates alter lipids, apolipoproteins and inflammatory
      markers in persons without HIV. The objective of this study was to evaluate
      changes in lipoproteins, apolipoproteins and other markers of inflammation with
      the use of pravastatin and fenofibrate. DESIGN: Evaluation of participants in
      ACTG A5087, a randomized trial of pravastatin 40 mg/day or fenofibrate 200 mg/day
      for the treatment of dyslipidemia. Participants that failed single-agent therapy
      at week 12 were given the combination. METHODS: Participants with available
      specimens were tested for apolipoproteins A1 and B, adiponectin, plasminogen
      activator inhibitor type 1 (PAI-1), P-selectin, and high-sensitivity C-reactive
      protein (hs-CRP). RESULTS: 74 participants (37 per randomized arm) received
      either pravastatin or fenofibrate for 12 weeks with 60 receiving combination
      treatment from weeks 12-48. There were no significant changes in hs-CRP, PAI-1,
      and P-selectin. From baseline to week 12, the median Apo B levels (-8 mg/dL,
      P=0.01 for fenofibrate and -27 mg/dL, P<0.01 for pravastatin) and ApoB/A1 ratios
      (-0.16, P<0.01 for both arms) significantly decreased. From baseline to week 48,
      median adiponectin (-1 ng/dL, P<0.01), Apo B (-22 mg/dL, P<0.01) and Apo B/A1
      ratios (-0.2, P<0.01) all decreased in those who went on combination therapy,
      whereas Apo A1 (9.5 mg/dL, P=0.01) levels increased. CONCLUSION: Treatment with
      pravastatin or fenofibrate improves the atherogenic lipid profile within the
      first 12 weeks and is sustained through 48 weeks with combination therapy.
      Adiponectin levels decrease with lipid-lowering therapy. However, markers of
      inflammation and platelet activation were not appreciably changed suggesting that
      the biologic properties of these agents differ in persons with HIV infection.

PMID- 20824153
TI  - Language in schizophrenia Part 2: What can psycholinguistics bring to the study
      of schizophrenia...and vice versa?
AB  - This is the second of two articles that discuss higher-order language and
      semantic processing in schizophrenia. The companion article (Part 1) gives an
      introduction to language dysfunction in schizophrenia patients. This article
      reviews a selection of psycholinguistic studies which suggest that sentence-level
      abnormalities in schizophrenia may stem from a relative overdependence on
      semantic associative relationships at the expense of building higher-order
      meaning. Language disturbances in schizophrenia may be best conceptualized as
      arising from an imbalance of activity across two streams of processing, one
      drawing upon semantic relationships within semantic memory and the other
      involving the use of combinatorial mechanisms to build propositional meaning. I
      will also discuss some of the ways in which the study of schizophrenia may offer
      new insights into the cognitive and neural architecture of the normal language
      system.

PMID- 20824154
TI  - Development of Practical Methodologies for the Synthesis of Functionalized
      Benzoboroxoles.
AB  - 2-Formylphenylboronic acids upon reaction with activated olefins such as
      acrylates, methyl vinyl ketone, and acrylonitrile, etc. provide functionalized
      benzoboroxoles. The corresponding homologated benzoboroxoles were synthesized via
      the reaction of 2-formylphenylboronic acids with alpha-bromomethylacrylates.

PMID- 20824155
TI  - Maximum-Likelihood Estimation With a Contracting-Grid Search Algorithm.
AB  - A fast search algorithm capable of operating in multi-dimensional spaces is
      introduced. As a sample application, we demonstrate its utility in the 2D and 3D
      maximum-likelihood position-estimation problem that arises in the processing of
      PMT signals to derive interaction locations in compact gamma cameras. We
      demonstrate that the algorithm can be parallelized in pipelines, and thereby
      efficiently implemented in specialized hardware, such as field-programmable gate
      arrays (FPGAs). A 2D implementation of the algorithm is achieved in Cell/BE
      processors, resulting in processing speeds above one million events per second,
      which is a 20* increase in speed over a conventional desktop machine. Graphics
      processing units (GPUs) are used for a 3D application of the algorithm, resulting
      in processing speeds of nearly 250,000 events per second which is a 250* increase
      in speed over a conventional desktop machine. These implementations indicate the
      viability of the algorithm for use in real-time imaging applications.

PMID- 20824156
TI  - Imaging Brain Dynamics Using Independent Component Analysis.
AB  - The analysis of electroencephalographic (EEG) and magnetoencephalographic (MEG)
      recordings is important both for basic brain research and for medical diagnosis
      and treatment. Independent component analysis (ICA) is an effective method for
      removing artifacts and separating sources of the brain signals from these
      recordings. A similar approach is proving useful for analyzing functional
      magnetic resonance brain imaging (fMRI) data. In this paper, we outline the
      assumptions underlying ICA and demonstrate its application to a variety of
      electrical and hemodynamic recordings from the human brain.

PMID- 20824157
TI  - Imaging dynamic cellular events with quantum dots The bright future.
AB  - Semiconductor quantum dots (QDs) are tiny light-emitting particles that have
      emerged as a new class of fluorescent labels for biology and medicine. Compared
      with traditional fluorescent probes, QDs have unique optical and electronic
      properties such as size-tuneable light emission, narrow and symmetric emission
      spectra, and broad absorption spectra that enable the simultaneous excitation of
      multiple fluorescence colours.

PMID- 20824158
TI  - Drosophila Gene Expression Pattern Annotation through Multi-Instance Multi-Label
      Learning.
AB  - The Berkeley Drosophila Genome Project (BDGP) has produced a large number of gene
      expression patterns, many of which have been annotated textually with anatomical
      and developmental terms. These terms spatially correspond to local regions of the
      images; however, they are attached collectively to groups of images, such that it
      is unknown which term is assigned to which region of which image in the group.
      This poses a challenge to the development of the computational method to automate
      the textual description of expression patterns contained in each image. In this
      paper, we show that the underlying nature of this task matches well with a new
      machine learning framework, Multi-Instance Multi-Label learning (MIML). We
      propose a new MIML support vector machine to solve the problems that beset the
      annotation task. Empirical study shows that the proposed method outperforms the
      state-of-the-art Drosophila gene expression pattern annotation methods.

PMID- 20824159
TI  - The evolution of HIV policy in Vietnam: from punitive control measures to a more
      rights-based approach.
AB  - AIM: Policymaking in Vietnam has traditionally been the preserve of the political
      elite, not open to the scrutiny of those outside the Communist Party. This paper
      aims to analyse Vietnam's HIV policy development in order to describe and
      understand the policy content, policy-making processes, actors and obstacles to
      policy implementation. METHODS: Nine policy documents on HIV were analysed and 17
      key informant interviews were conducted in Hanoi and Quang Ninh Province, based
      on a predesigned interview guide. Framework analysis, a type of qualitative
      content analysis, was applied for data analysis. RESULTS: Our main finding was
      that during the last two decades, developments in HIV policy in Vietnam were
      driven in a top-down way by the state organs, with support and resources coming
      from international agencies. Four major themes were identified: HIV policy
      content, the policy-making processes, the actors involved and human resources for
      policy implementation. Vietnam's HIV policy has evolved from one focused on
      punitive control measures to a more rights-based approach, encompassing harm
      reduction and payment of health insurance for medical costs of patients with HIV
      related illness. Low salaries and staff reluctance to work with patients, many of
      whom are drug users and female sex workers, were described as the main barriers
      to low health staff motivation. CONCLUSION: Health policy analysis approaches can
      be applied in a traditional one party state and can demonstrate how similar
      policy changes take place, as those found in pluralistic societies, but through
      more top-down and somewhat hidden processes. Enhanced participation of other
      actors, like civil society in the policy process, is likely to contribute to
      policy formulation and implementation that meets the diverse needs and concerns
      of its population.

PMID- 20824160
TI  - Elevated cAMP opposes (TNF-alpha)-induced loss in the barrier integrity of
      corneal endothelium.
AB  - PURPOSE: Elevated cyclic adenosine monophosphate (cAMP) enhances the barrier
      integrity of the corneal endothelium and thereby facilitates stromal hydration
      control, which is necessary for corneal transparency. This study investigates
      whether elevated cAMP is effective against the tumor necrosis factor-alpha (TNF
      alpha)-induced loss of barrier integrity in monolayers of bovine corneal
      endothelial cells (BCEC). METHODS: BCEC in primary culture were used for the
      study. Trans-endothelial electrical resistance (TER), a measure of barrier
      integrity, was determined by electrical cell-substrate impedance sensing. The
      changes were also ascertained by measuring paracellular permeability to
      fluorescein isothiocyanate (FITC)-dextran (10 kDa) across cells grown on porous
      culture inserts, and by immunofluorescence imaging of the apical junctional
      complex (AJC). The activation of p38 MAP kinase was assessed using western
      blotting. RESULTS: Co-treatment with forskolin, which activates adenylate
      cyclase, and rolipram, which inhibits cAMP-dependent phosphodiesterase PDE4,
      reduced the TNF-alpha-induced increase in the flux of FITC-dextran. Similar co
      treatment also prevented the TNF-alpha-induced disorganization of zona occludens
      1 (ZO-1) and cadherins at the AJC. Co-treatment, as well pre-treatment, with
      forskolin plus rolipram prevented the TNF-alpha-induced decrease in TER. The
      influence of the agents was significant after 12 h of exposure to the cytokine.
      This effect was also mimicked by A2B agonists, adenosine and 5'-N
      ethylcarboxamidoadenosine (NECA), which are known to mobilize cAMP in BCEC.
      Elevated cAMP also inhibited the cytokine-induced activation of p38 MAP kinase,
      and further blocked the disassembly of microtubules as well as the disruption of
      the PAMR (peri-junctional actomyosin ring) at the AJC. CONCLUSIONS: These results
      suggest that elevated cAMP opposes the TNF-alpha-induced loss in barrier
      integrity of the corneal endothelium. This effect follows inhibition of the
      cytokine-induced activation of p38 MAP kinase and its downstream signaling
      involved in the disruption of AJC and PAMR, as well as the disassembly of
      microtubules.

PMID- 20824161
TI  - Distinct olfactory signaling mechanisms in the malaria vector mosquito Anopheles
      gambiae.
AB  - Anopheles gambiae is the principal Afrotropical vector for human malaria, in
      which olfaction mediates a wide range of both adult and larval behaviors. Indeed,
      mosquitoes depend on the ability to respond to chemical cues for feeding, host
      preference, and mate location/selection. Building upon previous work that has
      characterized a large family of An. gambiae odorant receptors (AgORs), we now use
      behavioral analyses and gene silencing to examine directly the role of AgORs, as
      well as a newly identified family of candidate chemosensory genes, the An.
      gambiae variant ionotropic receptors (AgIRs), in the larval olfactory system. Our
      results validate previous studies that directly implicate specific AgORs in
      behavioral responses to DEET as well as other odorants and reveal the existence
      of at least two distinct olfactory signaling pathways that are active in An.
      gambiae. One system depends directly on AgORs; the other is AgOR-independent and
      requires the expression and activity of AgIRs. In addition to clarifying the
      mechanistic basis for olfaction in this system, these advances may ultimately
      enhance the development of vector control strategies, targeting olfactory
      pathways in mosquitoes to reduce the catastrophic effects of malaria and other
      mosquito-borne diseases.

PMID- 20824162
TI  - The somatic reproductive tissues of C. elegans promote longevity through steroid
      hormone signaling.
AB  - In Caenorhabditis elegans and Drosophila melanogaster, removing the germline
      precursor cells increases lifespan. In worms, and possibly also in flies, this
      lifespan extension requires the presence of somatic reproductive tissues. How the
      somatic gonad signals other tissues to increase lifespan is not known. The
      lifespan increase triggered by loss of the germ cells is known to require sterol
      hormone signaling, as reducing the activity of the nuclear hormone receptor DAF
      12, or genes required for synthesis of the DAF-12 ligand dafachronic acid,
      prevents germline loss from extending lifespan. In addition to sterol signaling,
      the FOXO transcription factor DAF-16 is required to extend lifespan in animals
      that lack germ cells. DAF-12/NHR is known to assist with the nuclear accumulation
      of DAF-16/FOXO in these animals, yet we find that loss of DAF-12/NHR has little
      or no effect on the expression of at least some DAF-16/FOXO target genes. In this
      study, we show that the DAF-12-sterol signaling pathway has a second function to
      activate a distinct set of genes and extend lifespan in response to the somatic
      reproductive tissues. When germline-deficient animals lacking somatic
      reproductive tissues are given dafachronic acid, their expression of DAF-12/NHR
      dependent target genes is restored and their lifespan is increased. Together, our
      findings indicate that in C. elegans lacking germ cells, the somatic reproductive
      tissues promote longevity via steroid hormone signaling to DAF-12.

PMID- 20824163
TI  - Seabird bycatch in pelagic longline fisheries is grossly underestimated when
      using only haul data.
AB  - Hundreds of thousands of seabirds are killed each year as bycatch in longline
      fisheries. Seabirds are predominantly caught during line setting but bycatch is
      generally recorded during line hauling, many hours after birds are caught. Bird
      loss during this interval may lead to inaccurate bycatch information. In this 15
      year study, seabird bycatch was recorded during both line setting and line
      hauling from four fishing regions: Indian Ocean, Southern Ocean, Coral Sea and
      central Pacific Ocean. Over 43,000 albatrosses, petrels and skuas representing
      over 25 species were counted during line setting of which almost 6,000 seabirds
      attempted to take the bait. Bait-taking interactions were placed into one of four
      categories. (i) The majority (57%) of bait-taking attempts were "unsuccessful"
      involving seabirds that did not take the bait nor get caught or hooked. (ii) One
      third of attempts were "successful" with seabirds removing the bait while not
      getting caught. (iii) One-hundred and seventy-six seabirds (3% of attempts) were
      observed being "caught" during line setting, with three albatross species -
      Laysan (Phoebastria immutabilis), black-footed (P. nigripes) and black-browed
      (Thalassarche melanophrys)- dominating this category. However, of these, only 85
      (48%) seabird carcasses were retrieved during line hauling. Most caught seabirds
      were hooked through the bill. (iv) The remainder of seabird-bait interactions
      (7%) was not clearly observed, but likely involved more "caught" seabirds. Bait
      taking attempts and percentage outcome (e.g. successful, caught) varied between
      seabird species and was not always related to species abundance around fishing
      vessels. Using only haul data to calculate seabird bycatch grossly underestimates
      actual bycatch levels, with the level of seabird bycatch from pelagic longline
      fishing possibly double what was previously thought.

PMID- 20824164
TI  - A novel preprocessing method using Hilbert Huang Transform for MALDI-TOF and
      SELDI-TOF mass spectrometry data.
AB  - MOTIVATION: Mass spectrometry is a high throughput, fast, and accurate method of
      protein analysis. Using the peaks detected in spectra, we can compare a normal
      group with a disease group. However, the spectrum is complicated by scale
      shifting and is also full of noise. Such shifting makes the spectra non
      stationary and need to align before comparison. Consequently, the preprocessing
      of the mass data plays an important role during the analysis process. Noises in
      mass spectrometry data come in lots of different aspects and frequencies. A
      powerful data preprocessing method is needed for removing large amount of noises
      in mass spectrometry data. RESULTS: Hilbert-Huang Transformation is a non
      stationary transformation used in signal processing. We provide a novel algorithm
      for preprocessing that can deal with MALDI and SELDI spectra. We use the Hilbert
      Huang Transformation to decompose the spectrum and filter-out the very high
      frequencies and very low frequencies signal. We think the noise in mass
      spectrometry comes from many sources and some of the noises can be removed by
      analysis of signal frequency domain. Since the protein in the spectrum is
      expected to be a unique peak, its frequency domain should be in the middle part
      of frequency domain and will not be removed. The results show that HHT, when used
      for preprocessing, is generally better than other preprocessing methods. The
      approach not only is able to detect peaks successfully, but HHT has the advantage
      of denoising spectra efficiently, especially when the data is complex. The
      drawback of HHT is that this approach takes much longer for the processing than
      the wavlet and traditional methods. However, the processing time is still
      manageable and is worth the wait to obtain high quality data.

PMID- 20824165
TI  - A simple colorimetric assay for specific detection of glutathione-S transferase
      activity associated with DDT resistance in mosquitoes.
AB  - BACKGROUND: Insecticide-based methods represent the most effective means of
      blocking the transmission of vector borne diseases. However, insecticide
      resistance poses a serious threat and there is a need for tools, such as
      diagnostic tests for resistance detection, that will improve the sustainability
      of control interventions. The development of such tools for metabolism-based
      resistance in mosquito vectors lags behind those for target site resistance
      mutations. METHODOLOGY/PRINCIPAL FINDINGS: We have developed and validated a
      simple colorimetric assay for the detection of Epsilon class Glutathione
      transferases (GST)-based DDT resistance in mosquito species, such as Aedes
      aegypti, the major vector of dengue and yellow fever worldwide. The colorimetric
      assay is based on the specific alkyl transferase activity of Epsilon GSTs for the
      haloalkene substrate iodoethane, which produces a dark blue colour highly
      correlated with AaGSTE2-2-overexpression in individual mosquitoes. The colour can
      be measured visually and spectrophotometrically. CONCLUSIONS/SIGNIFICANCE: The
      novel assay is substantially more sensitive compared to the gold standard CDNB
      assay and allows the discrimination of moderate resistance phenotypes. We
      anticipate that it will have direct application in routine vector monitoring as a
      resistance indicator and possibly an important impact on disease vector control.

PMID- 20824167
TI  - Firing hot, firing cold: how poikilotherms compensate for temperature swings.

PMID- 20824166
TI  - The perilipin homologue, lipid storage droplet 2, regulates sleep homeostasis and
      prevents learning impairments following sleep loss.
AB  - Extended periods of waking result in physiological impairments in humans, rats,
      and flies. Sleep homeostasis, the increase in sleep observed following sleep
      loss, is believed to counter the negative effects of prolonged waking by
      restoring vital biological processes that are degraded during sleep deprivation.
      Sleep homeostasis, as with other behaviors, is influenced by both genes and
      environment. We report here that during periods of starvation, flies remain
      spontaneously awake but, in contrast to sleep deprivation, do not accrue any of
      the negative consequences of prolonged waking. Specifically, the homeostatic
      response and learning impairments that are a characteristic of sleep loss are not
      observed following prolonged waking induced by starvation. Recently, two genes,
      brummer (bmm) and Lipid storage droplet 2 (Lsd2), have been shown to modulate the
      response to starvation. bmm mutants have excess fat and are resistant to
      starvation, whereas Lsd2 mutants are lean and sensitive to starvation. Thus, we
      hypothesized that bmm and Lsd2 may play a role in sleep regulation. Indeed, bmm
      mutant flies display a large homeostatic response following sleep deprivation. In
      contrast, Lsd2 mutant flies, which phenocopy aspects of starvation as measured by
      low triglyceride stores, do not exhibit a homeostatic response following sleep
      loss. Importantly, Lsd2 mutant flies are not learning impaired after sleep
      deprivation. These results provide the first genetic evidence, to our knowledge,
      that lipid metabolism plays an important role in regulating the homeostatic
      response and can protect against neuronal impairments induced by prolonged
      waking.

PMID- 20824168
TI  - Precise temperature compensation of phase in a rhythmic motor pattern.
AB  - Most animal species are cold-blooded, and their neuronal circuits must maintain
      function despite environmental temperature fluctuations. The central pattern
      generating circuits that produce rhythmic motor patterns depend on the orderly
      activation of circuit neurons. We describe the effects of temperature on the
      pyloric rhythm of the stomatogastric ganglion of the crab, Cancer borealis. The
      pyloric rhythm is a triphasic motor pattern in which the Pyloric Dilator (PD),
      Lateral Pyloric (LP), and Pyloric (PY) neurons fire in a repeating sequence.
      While the frequency of the pyloric rhythm increased about 4-fold (Q(10)
      approximately 2.3) as the temperature was shifted from 7 degrees C to 23 degrees
      C, the phase relationships of the PD, LP, and PY neurons showed almost perfect
      temperature compensation. The Q(10)'s of the input conductance, synaptic
      currents, transient outward current (I(A)), and the hyperpolarization-activated
      inward current (I(h)), all of which help determine the phase of LP neuron
      activity, ranged from 1.8 to 4. We studied the effects of temperature in >1,000
      computational models (with different sets of maximal conductances) of a bursting
      neuron and the LP neuron. Many bursting models failed to monotonically increase
      in frequency as temperature increased. Temperature compensation of LP neuron
      phase was facilitated when model neurons' currents had Q(10)'s close to 2.
      Together, these data indicate that although diverse sets of maximal conductances
      may be found in identified neurons across animals, there may be strong
      evolutionary pressure to restrict the Q(10)'s of the processes that contribute to
      temperature compensation of neuronal circuits.

PMID- 20824170
TI  - Roles of small GTPase Rac1 in the regulation of actin cytoskeleton during dengue
      virus infection.
AB  - BACKGROUND: Increased vascular permeability is a hallmark feature in severe
      dengue virus (DV) infection, and dysfunction of endothelial cells has been
      speculated to contribute in the pathogenesis of dengue hemorrhagic fever/dengue
      shock syndrome (DHF/DSS). Rho-family GTPase Rac1 is a significant element of
      endothelial barrier function regulation and has been implicated in the regulation
      of actin remodeling and intercellular junction formation. Yet there is little
      evidence linking Rac1 GTPase to alteration in endothelial cell function induced
      by DV infection. METHODS AND FINDINGS: Here, we showed that actin is essential
      for DV serotype 2 (DV2) entry into and release from ECV304 cells, and Rac1
      signaling is involved these processes. At early infection, actin cytoskeleton
      rearranged significantly during 1 hour post infection, and disrupting actin
      filament dynamics with jasplakinolide or cytochalasin D reduced DV2 entry. DV2
      entry induced reduction of Rac1 activity within 1 hour post infection. The
      expression of dominant-negative forms of Rac1 established that DV2 entry is
      negatively regulated by Rac1. At late infection, actin drugs also inhibited the
      DV2 release and induced accumulation of viral proteins in the cytoplasm.
      Meanwhile, the activity of Rac1 increased significantly with the progression of
      DV2 infection and was up-regulated in transfected cells expressing E protein.
      Confocal microscopy showed that DV2 E protein was closely associated with either
      actin or Rac1 in DV2-infected cells. The interaction between E protein and actin
      was further confirmed by co-immunoprecipitation assay. CONCLUSIONS: These results
      defined roles for actin integrity in DV2 entry and release, and indicated
      evidence for the participation of Rac1 signaling pathways in DV2-induced actin
      reorganizations and E-actin interaction. Our results may provide further insight
      into the pathogenesis of DHF/DSS.

PMID- 20824169
TI  - Cheminformatics-based drug design approach for identification of inhibitors
      targeting the characteristic residues of MMP-13 hemopexin domain.
AB  - BACKGROUND: MMP-13, a zinc dependent protease which catalyses the cleavage of
      type II collagen, is expressed in osteoarthritis (OA) and rheumatoid arthritis
      (RA) patients, but not in normal adult tissues. Therefore, the protease has been
      intensively studied as a target for the inhibition of progression of OA and RA.
      Recent reports suggest that selective inhibition of MMP-13 may be achieved by
      targeting the hemopexin (Hpx) domain of the protease, which is critical for
      substrate specificity. In this study, we applied a cheminformatics-based drug
      design approach for the identification and characterization of inhibitors
      targeting the amino acid residues characteristic to Hpx domain of MMP-13; these
      inhibitors may potentially be employed in the treatment of OA and RA.
      METHODOLOGY/PRINCIPAL FINDINGS: Sequence-based mutual information analysis
      revealed five characteristic (completely conserved and unique), putative
      functional residues of the Hpx domain of MMP-13 (these residues hereafter are
      referred to as HCR-13(pf)). Binding of a ligand to as many of the HCR-13(pf) is
      postulated to result in an increased selective inhibition of the Hpx domain of
      MMP-13. Through the in silico structure-based high-throughput virtual screening
      (HTVS) method of Glide, against a large public library of 16908 molecules from
      Maybridge, PubChem and Binding, we identified 25 ligands that interact with at
      least one of the HCR-13(pf). Assessment of cross-reactivity of the 25 ligands
      with MMP-1 and MMP-8, members of the collagenase family as MMP-13, returned seven
      lead molecules that did not bind to any one of the putative functional residues
      of Hpx domain of MMP-1 and any of the catalytic active site residues of MMP-1 and
      -8, suggesting that the ligands are not likely to interact with the functional or
      catalytic residues of other MMPs. Further, in silico analysis of physicochemical
      and pharmacokinetic parameters based on Lipinski's rule of five and ADMET
      (absorption, distribution, metabolism, excretion and toxicity) respectively,
      suggested potential utility of the compounds as drug leads.
      CONCLUSIONS/SIGNIFICANCE: We have identified seven distinct drug-like molecules
      binding to the HCR-13(pf) of MMP-13 with no observable cross-reactivity to MMP-1
      and MMP-8. These molecules are potential selective inhibitors of MMP-13 that can
      be experimentally validated and their backbone structural scaffold could serve as
      building blocks in designing drug-like molecules for OA, RA and other
      inflammatory disorders. The systematic cheminformatics-based drug design approach
      applied herein can be used for rational search of other public/commercial
      combinatorial libraries for more potent molecules, capable of selectively
      inhibiting the collagenolytic activity of MMP-13.

PMID- 20824171
TI  - Finding the right questions: exploratory pathway analysis to enhance biological
      discovery in large datasets.
AB  - This Essay discusses the role of pathways for exploratory data analysis in
      present-day biology.

PMID- 20824172
TI  - Physical activity attenuates the genetic predisposition to obesity in 20,000 men
      and women from EPIC-Norfolk prospective population study.
AB  - BACKGROUND: We have previously shown that multiple genetic loci identified by
      genome-wide association studies (GWAS) increase the susceptibility to obesity in
      a cumulative manner. It is, however, not known whether and to what extent this
      genetic susceptibility may be attenuated by a physically active lifestyle. We
      aimed to assess the influence of a physically active lifestyle on the genetic
      predisposition to obesity in a large population-based study. METHODS AND
      FINDINGS: We genotyped 12 SNPs in obesity-susceptibility loci in a population
      based sample of 20,430 individuals (aged 39-79 y) from the European Prospective
      Investigation of Cancer (EPIC)-Norfolk cohort with an average follow-up period of
      3.6 y. A genetic predisposition score was calculated for each individual by
      adding the body mass index (BMI)-increasing alleles across the 12 SNPs. Physical
      activity was assessed using a self-administered questionnaire. Linear and
      logistic regression models were used to examine main effects of the genetic
      predisposition score and its interaction with physical activity on BMI/obesity
      risk and BMI change over time, assuming an additive effect for each additional
      BMI-increasing allele carried. Each additional BMI-increasing allele was
      associated with 0.154 (standard error [SE] 0.012) kg/m(2) (p = 6.73 x 10(-37))
      increase in BMI (equivalent to 445 g in body weight for a person 1.70 m tall).
      This association was significantly (p(interaction) = 0.005) more pronounced in
      inactive people (0.205 [SE 0.024] kg/m(2) [p = 3.62 x 10(-18); 592 g in weight])
      than in active people (0.131 [SE 0.014] kg/m(2) [p = 7.97 x 10(-21); 379 g in
      weight]). Similarly, each additional BMI-increasing allele increased the risk of
      obesity 1.116-fold (95% confidence interval [CI] 1.093-1.139, p = 3.37 x 10(-26))
      in the whole population, but significantly (p(interaction) = 0.015) more in
      inactive individuals (odds ratio [OR] = 1.158 [95% CI 1.118-1.199; p = 1.93 x 10(
      16)]) than in active individuals (OR = 1.095 (95% CI 1.068-1.123; p = 1.15 x 10(
      12)]). Consistent with the cross-sectional observations, physical activity
      modified the association between the genetic predisposition score and change in
      BMI during follow-up (p(interaction) = 0.028). CONCLUSIONS: Our study shows that
      living a physically active lifestyle is associated with a 40% reduction in the
      genetic predisposition to common obesity, as estimated by the number of risk
      alleles carried for any of the 12 recently GWAS-identified loci. Please see later
      in the article for the Editors' Summary.

PMID- 20824173
TI  - Multi-country evaluation of the sensitivity and specificity of two commercially
      available NS1 ELISA assays for dengue diagnosis.
AB  - BACKGROUND: Early diagnosis of dengue can assist patient triage and management
      and prevent unnecessary treatments and interventions. Commercially available
      assays that detect the dengue virus protein NS1 in the plasma/serum of patients
      offers the possibility of early and rapid diagnosis. METHODOLOGY/PRINCIPAL
      FINDINGS: The sensitivity and specificity of the Pan-E Dengue Early ELISA and the
      Platelia Dengue NS1 Ag assays were compared against a reference diagnosis in 1385
      patients in 6 countries in Asia and the Americas. Platelia was more sensitive
      (66%) than Pan-E (52%) in confirmed dengue cases. Sensitivity varied by
      geographic region, with both assays generally being more sensitive in patients
      from SE Asia than the Americas. Both kits were more sensitive for specimens
      collected within the first few days of illness onset relative to later time
      points. Pan-E and Platelia were both 100% specific in febrile patients without
      evidence of acute dengue. In patients with other confirmed diagnoses and healthy
      blood donors, Platelia was more specific (100%) than Pan-E (90%). For Platelia,
      when either the NS1 test or the IgM test on the acute sample was positive, the
      sensitivity versus the reference result was 82% in samples collected in the first
      four days of fever. NS1 sensitivity was not associated to disease severity (DF or
      DHF) in the Platelia test, whereas a trend for higher sensitivity in DHF cases
      was seen in the Pan-E test (however combined with lower overall sensitivity).
      CONCLUSIONS/SIGNIFICANCE: Collectively, this multi-country study suggests that
      the best performing NS1 assay (Platelia) had moderate sensitivity (median 64%,
      range 34-76%) and high specificity (100%) for the diagnosis of dengue. The poor
      sensitivity of the evaluated assays in some geographical regions suggests further
      assessments are needed. The combination of NS1 and IgM detection in samples
      collected in the first few days of fever increased the overall dengue diagnostic
      sensitivity.

PMID- 20824174
TI  - Functional genome annotation by combined analysis across microarray studies of
      Trypanosoma brucei.
AB  - BACKGROUND: Functional annotation of trypanosomatid genomes has been a daunting
      task due to the low similarity of their genes with annotated genes of other
      organisms. Three recent studies have provided gene expression profiles in several
      different conditions and life stages for one of the main disease-causing
      trypanosomatids, Trypanosoma brucei. These data can be used to study the gene
      functions and regulatory mechanisms in this organism. METHODOLOGY/PRINCIPAL
      FINDINGS: Combining the data from three different microarray studies of T.
      brucei, we show that functional linkages among T. brucei genes can be identified
      based on gene coexpression, leading to a powerful approach for gene function
      prediction. These predictions can be further improved by considering the
      expression profiles of orthologous genes from other trypanosomatids. Furthermore,
      gene expression profiles can be used to discover potential regulatory elements
      within 3' untranslated regions. CONCLUSIONS/SIGNIFICANCE: These results suggest
      that although trypanosomatids do not regulate genes at transcription level,
      trypanosomatid genes with related functions are coregulated post
      transcriptionally via modulation of mRNA stability, implying the presence of
      complex regulatory networks in these organisms. Our analysis highlights the
      demand for a thorough transcript profiling of T. brucei genome in parallel with
      other trypanosomatid genomes, which can provide a powerful means to improve their
      functional annotation.

PMID- 20824175
TI  - Quantifying the impoverishing effects of purchasing medicines: a cross-country
      comparison of the affordability of medicines in the developing world.
AB  - BACKGROUND: Increasing attention is being paid to the affordability of medicines
      in low- and middle-income countries (LICs and MICs) where medicines are often
      highly priced in relation to income levels. The impoverishing effect of medicine
      purchases can be estimated by determining pre- and postpayment incomes, which are
      then compared to a poverty line. Here we estimate the impoverishing effects of
      four medicines in 16 LICs and MICs using the impoverishment method as a metric of
      affordability. METHODS AND FINDINGS: Affordability was assessed in terms of the
      proportion of the population being pushed below US$1.25 or US$2 per day poverty
      levels because of the purchase of medicines. The prices of salbutamol 100
      mcg/dose inhaler, glibenclamide 5 mg cap/tab, atenolol 50 mg cap/tab, and
      amoxicillin 250 mg cap/tab were obtained from facility-based surveys undertaken
      using a standard measurement methodology. The World Bank's World Development
      Indicators provided household expenditure data and information on income
      distributions. In the countries studied, purchasing these medicines would
      impoverish large portions of the population (up to 86%). Originator brand
      products were less affordable than the lowest-priced generic equivalents. In the
      Philippines, for example, originator brand atenolol would push an additional 22%
      of the population below US$1.25 per day, whereas for the lowest priced generic
      equivalent this demographic shift is 7%. Given related prevalence figures,
      substantial numbers of people are affected by the unaffordability of medicines.
      CONCLUSIONS: Comparing medicine prices to available income in LICs and MICs shows
      that medicine purchases by individuals in those countries could lead to the
      impoverishment of large numbers of people. Action is needed to improve medicine
      affordability, such as promoting the use of quality assured, low-priced generics,
      and establishing health insurance systems. Please see later in the article for
      the Editors' Summary.

PMID- 20824176
TI  - Challenges in developing evidence-based recommendations using the GRADE approach:
      the case of mental, neurological, and substance use disorders.

PMID- 20824177
TI  - Social relationships are key to health, and to health policy.

PMID- 20824178
TI  - Neglected tropical disease control in the "post-American world".

PMID- 20824179
TI  - Developmental Continuity and Stability of Emotional Availability in the Family:
      Two Ages and Two Genders in Child-Mother Dyads from Two Regions in Three
      Countries.
AB  - This study employs an intra-national and cross-national, prospective and
      longitudinal design to examine age, gender, region, and country variation in
      group mean-level continuity and individual-differences stability of emotional
      availability in child-mother dyads. Altogether, 220 Argentine, Italian, and U.S.
      American metropolitan and rural residence mothers and their daughters and sons
      were observed at home when children were 5 and 20 months of age. Similar patterns
      of continuity and discontinuity of emotional availability from 5 to 20 months
      were observed across regions and countries, but not between genders. Stability of
      emotional availability from 5 to 20 months was moderate and similar across
      genders, regions, and countries. Universal and gender-specific developmental
      processes in child-mother emotional availability as revealed in intra- and cross
      national study are discussed.

PMID- 20824180
TI  - Genital Appearance Dissatisfaction: Implications for Women's Genital Image Self
      Consciousness, Sexual Esteem, Sexual Satisfaction, and Sexual Risk.
AB  - Findings regarding the link between body image and sexuality have been equivocal,
      possibly because of the insensitivity of many of body image measures to potential
      variability across sensory aspects of the body (e.g., appearance versus odor),
      individual body parts (e.g., genitalia versus thighs), and social settings (e.g.,
      public versus intimate). The current study refined existing methods of evaluating
      women's body image in the context of sexuality by focusing upon two highly
      specified dimensions: satisfaction with the visual appearance of the genitalia
      and self-consciousness about the genitalia during a sexual encounter. Genital
      appearance dissatisfaction, genital image self-consciousness, and multiple facets
      of sexuality were examined with a sample of 217 undergraduate women using an
      online survey. Path analysis revealed that greater dissatisfaction with genital
      appearance was associated with higher genital image self-consciousness during
      physical intimacy, which, in turn, was associated with lower sexual esteem,
      sexual satisfaction, and motivation to avoid risky sexual behavior. These
      findings underscore the detrimental impact of negative genital perceptions on
      young women's sexual wellbeing, which is of particular concern given their
      vulnerability at this stage of sexual development as well as the high rates of
      sexually transmitted infections within this age group. Interventions that enhance
      satisfaction with the natural appearance of their genitalia could facilitate the
      development of a healthy sexual self-concept and provide long-term benefits in
      terms of sexual safety and satisfaction.

PMID- 20824181
TI  - What Are Key Factors in Haitian and Hispanic Children and Obesity: Parent
      Answers.

PMID- 20824182
TI  - Point of View: In the eye of the beholder: Preferences of patients, family
      physicians, and surgeons for lumbar spinal surgery.

PMID- 20824184
TI  - Harnessing naturally occurring tumor immunity: a clinical vaccine trial in
      prostate cancer.
AB  - BACKGROUND: Studies of patients with paraneoplastic neurologic disorders (PND)
      have revealed that apoptotic tumor serves as a potential potent trigger for the
      initiation of naturally occurring tumor immunity. The purpose of this study was
      to assess the feasibility, safety, and immunogenicity of an apoptotic tumor
      autologous dendritic cell (DC) vaccine. METHODS AND FINDINGS: We have modeled PND
      tumor immunity in a clinical trial in which apoptotic allogeneic prostate tumor
      cells were used to generate an apoptotic tumor-autologous dendritic cell vaccine.
      Twenty-four prostate cancer patients were immunized in a Phase I, randomized,
      single-blind, placebo-controlled study to assess the safety and immunogenicity of
      this vaccine. Vaccinations were safe and well tolerated. Importantly, we also
      found that the vaccine was immunogenic, inducing delayed type hypersensitivity
      (DTH) responses and CD4+ and CD8+ T cell proliferation, with no effect on FoxP3+
      regulatory T cells. A statistically significant increase in T cell proliferation
      responses to prostate tumor cells in vitro (p = 0.002), decrease in prostate
      specific antigen (PSA) slope (p = 0.016), and a two-fold increase in PSA doubling
      time (p = 0.003) were identified when we compared data before and after
      vaccination. CONCLUSIONS: An apoptotic cancer cell vaccine modeled on naturally
      occurring tumor immune responses in PND patients provides a safe and immunogenic
      tumor vaccine. TRIAL REGISTRATION: ClinicalTrials.gov NCT00289341.

PMID- 20824185
TI  - Fruit and soil quality of organic and conventional strawberry agroecosystems.
AB  - BACKGROUND: Sale of organic foods is one of the fastest growing market segments
      within the global food industry. People often buy organic food because they
      believe organic farms produce more nutritious and better tasting food from
      healthier soils. Here we tested if there are significant differences in fruit and
      soil quality from 13 pairs of commercial organic and conventional strawberry
      agroecosystems in California. METHODOLOGY/PRINCIPAL FINDINGS: At multiple
      sampling times for two years, we evaluated three varieties of strawberries for
      mineral elements, shelf life, phytochemical composition, and organoleptic
      properties. We also analyzed traditional soil properties and soil DNA using
      microarray technology. We found that the organic farms had strawberries with
      longer shelf life, greater dry matter, and higher antioxidant activity and
      concentrations of ascorbic acid and phenolic compounds, but lower concentrations
      of phosphorus and potassium. In one variety, sensory panels judged organic
      strawberries to be sweeter and have better flavor, overall acceptance, and
      appearance than their conventional counterparts. We also found the organically
      farmed soils to have more total carbon and nitrogen, greater microbial biomass
      and activity, and higher concentrations of micronutrients. Organically farmed
      soils also exhibited greater numbers of endemic genes and greater functional gene
      abundance and diversity for several biogeochemical processes, such as nitrogen
      fixation and pesticide degradation. CONCLUSIONS/SIGNIFICANCE: Our findings show
      that the organic strawberry farms produced higher quality fruit and that their
      higher quality soils may have greater microbial functional capability and
      resilience to stress. These findings justify additional investigations aimed at
      detecting and quantifying such effects and their interactions.

PMID- 20824186
TI  - HPK1 associates with SKAP-HOM to negatively regulate Rap1-mediated B-lymphocyte
      adhesion.
AB  - BACKGROUND: Hematopoietic progenitor kinase 1 (HPK1) is a Ste20-related
      serine/threonine kinase activated by a range of environmental stimuli including
      genotoxic stress, growth factors, inflammatory cytokines and antigen receptor
      triggering. Being inducibly recruited to membrane-proximal signalling scaffolds
      to regulate NFAT, AP-1 and NFkappaB-mediated gene transcription in T-cells, the
      function of HPK1 in B-cells to date remains rather ill-defined.
      METHODOLOGY/PRINCIPAL FINDINGS: By using two loss of function models, we show
      that HPK1 displays a novel function in regulating B-cell integrin activity. Wehi
      231 lymphoma cells lacking HPK1 after shRNA mediated knockdown exhibit increased
      basic activation levels of Ras-related protein 1 (Rap1), accompanied by a severe
      lymphocyte function-associated antigen-1 (LFA-1) dependent homotypic aggregation
      and increased adhesion to intercellular adhesion molecule 1 (ICAM-1). The
      observed phenotype of enhanced integrin activity is caused downstream of Src, by
      a signalling module independent of PI3K and PLC, involving HPK1, SKAP55 homologue
      (SKAP-HOM) and Rap1-GTP-interacting adaptor molecule (RIAM). This alters actin
      dynamics and renders focal adhesion kinase (FAK) constitutively phosphorylated.
      Bone marrow and splenic B-cell development of HPK1(-/-) mice are largely
      unaffected, except age-related tendencies for increased splenic cellularity and
      BCR downregulation. In addition, naive splenic knockout B-cells appear
      hyperresponsive to a range of stimuli applied ex vivo as recently demonstrated by
      others for T-cells. CONCLUSIONS/SIGNIFICANCE: We therefore conclude that HPK1
      exhibits a dual function in B-cells by negatively regulating integrin activity
      and controlling cellular activation, which makes it an interesting candidate to
      study in pathological settings like autoimmunity and cancer.

PMID- 20824187
TI  - Amino-acid co-variation in HIV-1 Gag subtype C: HLA-mediated selection pressure
      and compensatory dynamics.
AB  - BACKGROUND: Despite high potential for HIV-1 genetic variation, the emergence of
      some mutations is constrained by fitness costs, and may be associated with
      compensatory amino acid (AA) co-variation. To characterize the interplay between
      Cytotoxic T Lymphocyte (CTL)-mediated pressure and HIV-1 evolutionary pathways,
      we investigated AA co-variation in Gag sequences obtained from 449 South African
      individuals chronically infected with HIV-1 subtype C. METHODOLOGY/PRINCIPAL
      FINDINGS: Individuals with CTL responses biased toward Gag presented lower viral
      loads than individuals with under-represented Gag-specific CTL responses. Using
      methods that account for founder effects and HLA linkage disequilibrium, we
      identified 35 AA sites under Human Leukocyte Antigen (HLA)-restricted CTL
      selection pressure and 534 AA-to-AA interactions. Analysis of two-dimensional
      distances between co-varying residues revealed local stabilization mechanisms
      since 40% of associations involved neighboring residues. Key features of our co
      variation analysis included sites with a high number of co-varying partners, such
      as HLA-associated sites, which had on average 55% more connections than other co
      varying sites. CONCLUSIONS/SIGNIFICANCE: Clusters of co-varying AA around HLA
      associated sites (especially at typically conserved sites) suggested that
      cooperative interactions act to preserve the local structural stability and
      protein function when CTL escape mutations occur. These results expose HLA
      imprinted HIV-1 polymorphisms and their interlinked mutational paths in Gag that
      are likely due to opposite selective pressures from host CTL-mediated responses
      and viral fitness constraints.

PMID- 20824188
TI  - Enhanced immunogenicity of stabilized trimeric soluble influenza hemagglutinin.
AB  - BACKGROUND: The recent swine-origin H1N1 pandemic illustrates the need to develop
      improved procedures for rapid production of influenza vaccines. One alternative
      to the current egg-based manufacture of influenza vaccine is to produce a
      hemagglutinin (HA) subunit vaccine using a recombinant expression system with the
      potential for high protein yields, ease of cloning new antigenic variants, and an
      established safety record in humans. METHODOLOGY/PRINCIPAL FINDINGS: We generated
      a soluble HA (sHA), derived from the H3N2 virus A/Aichi/2/68, modified at the C
      terminus with a GCN4pII trimerization repeat to stabilize the native trimeric
      structure of HA. When expressed in the baculovirus system, the modified sHA
      formed native trimers. In contrast, the unmodified sHA was found to present
      epitopes recognized by a low-pH conformation specific monoclonal antibody. We
      found that mice primed and boosted with 3 microg of trimeric sHA in the absence
      of adjuvants had significantly higher IgG and HAI titers than mice that received
      the unmodified sHA. This correlated with an increased survival and reduced body
      weight loss following lethal challenge with mouse-adapted A/Aichi/2/68 virus. In
      addition, mice receiving a single vaccination of the trimeric sHA in the absence
      of adjuvants had improved survival and body weight loss compared to mice
      vaccinated with the unmodified sHA. CONCLUSIONS/SIGNIFICANCE: Our data indicate
      that the recombinant trimeric sHA presents native trimeric epitopes while the
      unmodified sHA presents epitopes not exposed in the native HA molecule. The
      epitopes presented in the unmodified sHA constitute a "silent face" which may
      skew the antibody response to epitopes not accessible in live virus at neutral
      pH. The results demonstrate that the trimeric sHA is a more effective influenza
      vaccine candidate and emphasize the importance of structure-based antigen design
      in improving recombinant HA vaccines.

PMID- 20824189
TI  - Status of biodiversity in the Baltic Sea.
AB  - The brackish Baltic Sea hosts species of various origins and environmental
      tolerances. These immigrated to the sea 10,000 to 15,000 years ago or have been
      introduced to the area over the relatively recent history of the system. The
      Baltic Sea has only one known endemic species. While information on some abiotic
      parameters extends back as long as five centuries and first quantitative snapshot
      data on biota (on exploited fish populations) originate generally from the same
      time, international coordination of research began in the early twentieth
      century. Continuous, annual Baltic Sea-wide long-term datasets on several
      organism groups (plankton, benthos, fish) are generally available since the mid
      1950s. Based on a variety of available data sources (published papers, reports,
      grey literature, unpublished data), the Baltic Sea, incl. Kattegat, hosts
      altogether at least 6,065 species, including at least 1,700 phytoplankton, 442
      phytobenthos, at least 1,199 zooplankton, at least 569 meiozoobenthos, 1,476
      macrozoobenthos, at least 380 vertebrate parasites, about 200 fish, 3 seal, and
      83 bird species. In general, but not in all organism groups, high sub-regional
      total species richness is associated with elevated salinity. Although in
      comparison with fully marine areas the Baltic Sea supports fewer species, several
      facets of the system's diversity remain underexplored to this day, such as micro
      organisms, foraminiferans, meiobenthos and parasites. In the future, climate
      change and its interactions with multiple anthropogenic forcings are likely to
      have major impacts on the Baltic biodiversity.

PMID- 20824190
TI  - Y chromosomal variation tracks the evolution of mating systems in chimpanzee and
      bonobo.
AB  - The male-specific regions of the Y chromosome (MSY) of the human and the
      chimpanzee (Pan troglodytes) are fully sequenced. The most striking difference is
      the dramatic rearrangement of large parts of their respective MSYs. These non
      recombining regions include ampliconic gene families that are known to be
      important for male reproduction,and are consequently under significant selective
      pressure. However, whether the published Y-chromosomal pattern of ampliconic
      fertility genes is invariable within P. troglodytes is an open but fundamental
      question pertinent to discussions of the evolutionary fate of the Y chromosome in
      different primate mating systems. To solve this question we applied fluorescence
      in situ hybridisation (FISH) of testis-specific expressed ampliconic fertility
      genes to metaphase Y chromosomes of 17 chimpanzees derived from 11 wild-born
      males and 16 bonobos representing seven wild-born males. We show that of eleven
      P. troglodytes Y-chromosomal lines, ten Y-chromosomal variants were detected
      based on the number and arrangement of the ampliconic fertility genes DAZ
      (deleted in azoospermia) and CDY (chromodomain protein Y)-a so-far never
      described variation of a species' Y chromosome. In marked contrast, no variation
      was evident among seven Y-chromosomal lines of the bonobo, P. paniscus, the
      chimpanzee's closest living relative. Although, loss of variation of the Y
      chromosome in the bonobo by a founder effect or genetic drift cannot be excluded,
      these contrasting patterns might be explained in the context of the species'
      markedly different social and mating behaviour. In chimpanzees, multiple males
      copulate with a receptive female during a short period of visible anogenital
      swelling, and this may place significant selection on fertility genes. In
      bonobos, however, female mate choice may make sperm competition redundant
      (leading to monomorphism of fertility genes), since ovulation in this species is
      concealed by the prolonged anogenital swelling, and because female bonobos can
      occupy high-ranking positions in the group and are thus able to determine mate
      choice more freely.

PMID- 20824192
TI  - Selection, Preparation, and Evaluation of Small- Molecule Inhibitors of Toll-Like
      Receptor 4.
AB  - Toll-like receptor 4 (TLR4), a membrane spanning receptor protein that functions
      in complex with its accessory protein MD-2, is an intriguing target for
      therapeutic development. Herein we report the identification of a series of novel
      TLR4 inhibitors and the development of a robust, enantioselective synthesis using
      an unprecedented Mannich-type reaction to functionalize a pyrazole ring. In
      silico and cellular assay results demonstrated that compound 1 and its analogues
      selectively block TLR4 activation in live cells. Animal model tests showed that 1
      and its derivatives could potentiate morphine-induced analgesia in vivo,
      presumably by attenuating the opioid-induced TLR4 activation.

PMID- 20824191
TI  - Hippocampus specific iron deficiency alters competition and cooperation between
      developing memory systems.
AB  - Iron deficiency (ID) is the most common gestational micronutrient deficiency in
      the world, targets the fetal hippocampus and striatum and results in long-term
      behavioral abnormalities. These structures primarily mediate spatial and
      procedural memory, respectively, in the rodent but have interconnections that
      result in competition or cooperation during cognitive tasks. We determined
      whether ID-induced impairment of one alters the function of the other by
      genetically inducing a 40% reduction of hippocampus iron content in late fetal
      life in mice and measuring dorsal striatal gene expression and metabolism and the
      behavioral balance between the two memory systems in adulthood.
      Slc11a2(hipp/hipp) mice had similar striatum iron content, but 18% lower glucose
      and 44% lower lactate levels, a 30% higher phosphocreatine:creatine ratio, and
      reduced iron transporter gene expression compared to wild type (WT) littermates,
      implying reduced striatal metabolic function. Slc11a2(hipp/hipp) mice had longer
      mean escape times on a cued task paradigm implying impaired procedural memory.
      Nevertheless, when hippocampal and striatal memory systems were placed in
      competition using a Morris Water Maze task that alternates spatial navigation and
      visual cued responses during training, and forces a choice between hippocampal
      and striatal strategies during probe trials, Slc11a2(hipp/hipp) mice used the
      hippocampus-dependent response less often (25%) and the visual cued response more
      often (75%) compared to WT littermates that used both strategies approximately
      equally. Hippocampal ID not only reduces spatial recognition memory performance
      but also affects systems that support procedural memory, suggesting an altered
      balance between memory systems. ELECTRONIC SUPPLEMENTARY MATERIAL: The online
      version of this article (doi:10.1007/s11689-010-9049-0) contains supplementary
      material, which is available to authorized users.

PMID- 20824193
TI  - Psychiatric and Cognitive Functioning in Adolescent Inpatients with Histories of
      Dating Violence Victimization.
AB  - The presence of dating violence victimization as well as its relation to
      psychiatric diagnosis and cognitive processes was examined in a sample of 155
      adolescents hospitalized in a psychiatric facility. Participants and their
      parents completed semi-structured diagnostic interviews. Participants also
      completed self-report measures of dating violence victimization and cognitive
      functioning. Seventy-seven percent of adolescents who had initiated dating
      reported psychological, physical, and/or sexual abuse by a dating partner over
      the past year. Victims of psychological abuse alone as well as physical and/or
      sexual violence endorsed higher rates of major depressive disorder compared to
      non-victims. Physical/sexual dating violence victims also endorsed significantly
      higher rates of PTSD and alcohol use disorders, more frequent co-occurrence of
      externalizing and internalizing disorders, and more frequent negative cognitive
      biases, relative to non-victimized adolescents. Findings suggest that
      psychiatrically hospitalized adolescents with dating violence histories represent
      a subgroup of adolescent inpatients with a particularly serious clinical picture.

PMID- 20824194
TI  - Predictors of Maternal Sensitivity to Infant Distress.
AB  - OBJECTIVE: The present study was designed to examine the extent to which mothers'
      emotional (i.e., empathy, negative emotions) and cognitive (i.e., accurate
      detection of distress, goals about infant crying, and emotion efficacy) responses
      to infant distress are related to maternal sensitivity in tasks designed to
      elicit infant distress. Mothers' emotional and cognitive responses to distress
      were assessed both prenatally in response to unfamiliar infants and postnatally
      in response to own infant. The extent to which prenatal and postnatal measures
      correlated with one another and with sensitivity to distress was examined.
      DESIGN: One-hundred and one mothers were interviewed prenatally about their
      responses to videotapes of crying infants, then videotaped interacting with their
      own infants at 6-months postpartum in two emotionally arousing tasks during which
      maternal sensitivity and infant distress were rated, and participated in a video
      recall interview about their thoughts and feelings during the emotionally
      arousing tasks. RESULTS: Mothers' prenatal and postnatal goals in relation to
      infant distress and emotional reactions to infant distress were the most
      consistent predictors of sensitivity, but prenatal accurate detection of infant
      distress also predicted sensitivity. Furthermore, mothers' goals, emotional
      reactions to crying, and accurate distress detection buffered maternal
      sensitivity from the negative effect of observed infant distress. That is, infant
      distress was less strongly negatively associated with sensitivity when mothers
      had more infant-oriented goals, reported fewer negative emotions in response to
      infant crying, or were skilled at detecting infant distress. CONCLUSIONS:
      Assessing mothers' emotional and cognitive responses to infant distress provides
      insights into the origins of sensitivity to infant distress. Methodological
      issues relevant to assessing mothers' emotional and cognitive responses to infant
      distress are raised.

PMID- 20824195
TI  - Are both parents always better than one? Parental conflict and young adult well
      being.
AB  - Using data from three waves of the National Survey of Families and Households
      (N=1,963), we examine associations between adolescent family experiences and
      young adult well-being across a range of indicators, including schooling,
      substance use, and family-related transitions. We compare children living with
      both biological parents, but whose parents differ in how often they argue, to
      children in stepfather and single-mother families, and we assess the extent to
      which differences can be understood in terms of family income and parenting
      practices. Findings suggest that parental conflict is associated with children's
      poorer academic achievement, increased substance use, and early family formation
      and dissolution. Living in single mother and stepfather families tend to be more
      strongly associated with our indicators of well-being, although differences
      between these family types and living with high conflict continuously married
      parents are often statistically indistinguishable. Income and parenting largely
      do not account for associations between adolescent family type and later life
      outcomes. We conclude that while children do better, on average, living with two
      biological married parents, the advantages of two-parent families are not shared
      equally by all.

PMID- 20824196
TI  - The metamorphosis of heterometallic trinuclear antiferromagnetic complexes into
      nano-sized superparamagnetic spinels.
AB  - Thermal decomposition of the trinuclear heterometallic oxoacetates [Fe(2)M(MU(3)
      O)(CH(3)COO)(6)(H(2)O)(3)] has been used as a single-precursor method for
      synthesis of the spinel-structured ternary oxides MFe(2)O(4) (M = Mn(II), Co(II),
      and Ni(II)). This facile process occurring at 320  degrees C results in the
      formation of nanocrystalline, (7-20 nm) highly pure stoichiometric ferrites in
      quantitative yield. The magnetic properties of these nanoparticulate ferrites
      were studied in the 10-300 K temperature range, revealing superparamagnetic
      behaviour for the Ni and Mn particles and ferromagnetic behavior for the Co ones
      at room temperature. Their blocking temperatures follow the order: CoFe(2)O(4) >
      MnFe(2)O(4) > NiFe(2)O(4).

PMID- 20824197
TI  - Human-centeredness is Not a Universal Feature of Young Children's Reasoning:
      Culture and Experience Matter When Reasoning About Biological Entities.
AB  - We consider young children's construals of biological phenomena and the forces
      that shape them, using Carey's (1985) category-based induction task that
      demonstrated anthropocentric reasoning in young urban children. Follow-up studies
      (including our own) have questioned the generality of her results, but they have
      employed quite different procedures and either have not included urban children
      or, when urban samples were included, have failed to reproduce her original
      findings. In the present study of 4-10-year-olds from three cultural communities,
      our procedures followed Carey's more closely and replicated her findings with
      young urban children. However, they yielded quite different results for young
      rural European American and young rural Native American children. These results
      underscore the importance of a complex interaction of culture and experience-
      including both day-to-day interactions with the natural world and sensitivity to
      the belief systems of the communities--in children's reasoning about the natural
      world.

PMID- 20824198
TI  - ALCOHOL AND VIOLENCE-RELATED INJURIES AMONG EMERGENCY ROOM PATIENTS IN AN
      INTERNATIONAL PERSPECTIVE.
AB  - While alcohol has been found to be more closely associated with violence-related
      injury than with injury from other causes, little data is available which
      documents heterogeneity in this association across countries or cultures, taking
      into consideration usual drinking patterns and other socio-cultural variables.
      Data are reported from 15 countries comprising the Emergency Room Collaborative
      Alcohol Analysis Project and the WHO Collaborative Study on Alcohol and Injury.
      Case-crossover analysis was used to analyze the risk of injury (among current
      drinkers) from drinking six hours prior to the event, based on frequency of usual
      drinking, for violence-related injuries and separately for non-violence related
      injuries. Relative risk (RR) for a violence-related injury was significantly
      greater than for injuries from other causes across all countries (pooled RR=22.22
      vs. 4.33), but the magnitude of risk varied considerably (ranging from 4.68 in
      Spain to 942 in Canada). Pooled effect size was found to be heterogeneous across
      countries, and was explained, in part, by the level of detrimental drinking
      pattern in a country. Risk for a violence-related injury was not significantly
      different by age (<30 and 30+), reporting 5 or more drinks on at least one
      occasion during the last year, or reporting symptoms of alcohol dependence. A
      number of methodological concerns suggest that risk of a violence-related injury
      compared to injuries from other causes may be inflated, and such variables as
      context of drinking should be taken into consideration in establishing relative
      risk and alcohol attributable fraction of violence-related injury across
      countries and cultures.

PMID- 20824199
TI  - Structural, mechanical and osmotic properties of injectable hyaluronan-based
      composite hydrogels.
AB  - The osmotic and scattering properties of hyaluronan-based composite hydrogels
      composed of stiff biopolymer chains (carboxymethylated thiolated hyaluronan (CMHA
      S)) crosslinked by a flexible polymer (polyethylene glycol diacrylate (PEGDA))
      are investigated and analyzed in terms of the scaling theory. The total pre-gel
      polymer weight concentration is varied between 0.5 wt.% and 3.2 wt.%, while the
      mole ratio between the reactive PEG chain ends and the thiolated HA moieties is
      changed between 0.15 and 1.0. The shear modulus G of the fully swollen gels
      exhibits a stronger dependence on pre-gel concentration than on the crosslink
      density. Osmotic deswelling measurements reveal that the osmotic mixing pressure
      depends on the weight ratio CMHA-S/PEGDA, and is practically unaffected by the
      pre-gel concentration. Small-angle neutron scattering observations indicate that
      the thermodynamic properties of these composite gels are governed by total
      polymer concentration, i.e., specific interactions between the two polymeric
      components do not play a significant role.

PMID- 20824200
TI  - Self-generated Domains of Quality of Life in Children with and Without Cerebral
      Palsy.
AB  - This study was conducted to demonstrate feasibility of utilizing a modified
      SEIQoL-DW with children by examining self-generated domains of quality of life in
      children with and without cerebral palsy. Study samples were children, ages 6-12,
      (mean 8.9, SD 1.8) including 41 children with cerebral palsy (CP) and 60 children
      who were age and gender matched peers without disability. Quality of life was
      assessed with a modified Schedule for the Evaluation of Individual Quality of
      Life-Direct Weight (SEIQoL-DW). Group differences in overall ratings of quality
      of life were not significant; however, there were significant group differences
      in the frequency and hierarchy of self-generated domains. Within the group with
      CP, functional ability was not associated with quality of life.

PMID- 20824201
TI  - Incentivizing education: Seeing schoolwork as an investment, not a chore.
AB  - Most American children expect to attend college but because they do not
      necessarily spend much time on schoolwork, they may fail to reach their imagined
      "college-bound" future self. The proposed identity-based motivation model helps
      explain why this gap occurs: Imagined "college-bound" identities cue school
      focused behavior if they are salient and feel relevant to current choice options,
      not otherwise. Two studies with predominantly low-income and African American
      middle school students support this prediction. Almost all of the students expect
      to attend college, but only half describe education-dependent (e.g., law,
      medicine) adult identities. Having education-dependent rather than education
      independent adult identities (e.g., sports, entertainment) predicts better grades
      over time, controlling for prior grade point average (Study 1). To demonstrate
      causality, salience of education-dependent versus education-independent adult
      identities was experimentally manipulated. Children who considered education
      dependent adult identities (vs. education-independent ones) were eight times more
      likely to complete a take-home extra credit assignment (Study 2).

PMID- 20824202
TI  - Later-life Employment Preferences and Outcomes: The Role of Mid-life Work
      Experiences.
AB  - In this paper, we evaluate relationships between mid-life work experiences and
      the realization of preferences for full-time employment, part-time employment,
      and complete retirement at age 63-64. Using rich data from the Wisconsin
      Longitudinal Study, we demonstrate that the likelihood of achieving one's
      preferred employment status is related to earlier work experiences including
      employment stability in mid-life and self-employment, part-time employment, and
      private pension coverage across the life course. Despite large gender differences
      in work experiences across the life course, relationships between earlier work
      experiences and the likelihood of realizing later-life employment preferences are
      generally similar for men and women. We also find that these relationships are
      only partially mediated by economic and employment circumstances in late mid
      life, suggesting the need for further evaluation of the cumulative pathways
      linking mid-life work experiences to the realization of later-life employment
      preferences.

PMID- 20824203
TI  - EMMPRIN promotes melanoma cells malignant properties through a HIF-2alpha
      mediated up-regulation of VEGF-receptor-2.
AB  - EMMPRIN's expression in melanoma tissue was reported to be predictive of poor
      prognosis. Here we demonstrate that EMMPRIN up-regulated VEGF receptor-2 (VEGFR
      2) in two different primary melanoma cell lines and consequently increased
      migration and proliferation of these cells while inhibiting their apoptosis.
      SiRNA inhibition of VEGFR-2 expression abrogated these EMMPRIN effects. EMMPRIN
      regulation of VEGFR-2 was mediated through the over-expression of HIF-2alpha and
      its translocation to the nucleus where it forms heterodimers with HIF-1beta.
      These results were supported by an in vivo correlation between the expression of
      EMMPRIN with that of VEGFR-2 in human melanoma tissues as well as with the extent
      of HIF-2alpha localization in the nucleus. They demonstrate a novel mechanism by
      which EMMPRIN promotes tumor progression through HIF-2alpha/VEGFR-2 mediated
      mechanism, with an autocrine role in melanoma cell malignancy. The inhibition of
      EMMPRIN in cancer may thus simultaneously target both the VEGFR-2/VEGF system and
      the matrix degrading proteases to block tumor cell growth and invasion.

PMID- 20824204
TI  - From sea to sea: Canada's three oceans of biodiversity.
AB  - Evaluating and understanding biodiversity in marine ecosystems are both necessary
      and challenging for conservation. This paper compiles and summarizes current
      knowledge of the diversity of marine taxa in Canada's three oceans while
      recognizing that this compilation is incomplete and will change in the future.
      That Canada has the longest coastline in the world and incorporates distinctly
      different biogeographic provinces and ecoregions (e.g., temperate through ice
      covered areas) constrains this analysis. The taxonomic groups presented here
      include microbes, phytoplankton, macroalgae, zooplankton, benthic infauna,
      fishes, and marine mammals. The minimum number of species or taxa compiled here
      is 15,988 for the three Canadian oceans. However, this number clearly
      underestimates in several ways the total number of taxa present. First, there are
      significant gaps in the published literature. Second, the diversity of many
      habitats has not been compiled for all taxonomic groups (e.g., intertidal rocky
      shores, deep sea), and data compilations are based on short-term, directed
      research programs or longer-term monitoring activities with limited spatial
      resolution. Third, the biodiversity of large organisms is well known, but this is
      not true of smaller organisms. Finally, the greatest constraint on this summary
      is the willingness and capacity of those who collected the data to make it
      available to those interested in biodiversity meta-analyses. Confirmation of
      identities and intercomparison of studies are also constrained by the disturbing
      rate of decline in the number of taxonomists and systematists specializing on
      marine taxa in Canada. This decline is mostly the result of retirements of
      current specialists and to a lack of training and employment opportunities for
      new ones. Considering the difficulties encountered in compiling an overview of
      biogeographic data and the diversity of species or taxa in Canada's three oceans,
      this synthesis is intended to serve as a biodiversity baseline for a new program
      on marine biodiversity, the Canadian Healthy Ocean Network. A major effort needs
      to be undertaken to establish a complete baseline of Canadian marine biodiversity
      of all taxonomic groups, especially if we are to understand and conserve this
      part of Canada's natural heritage.

PMID- 20824205
TI  - Transcriptional reprogramming in nonhuman primate (rhesus macaque) tuberculosis
      granulomas.
AB  - BACKGROUND: In response to Mtb infection, the host remodels the infection foci
      into a dense mass of cells known as the granuloma. The key objective of the
      granuloma is to contain the spread of Mtb into uninfected regions of the lung.
      However, it appears that Mtb has evolved mechanisms to resist killing in the
      granuloma. Profiling granuloma transcriptome will identify key immune signaling
      pathways active during TB infection. Such studies are not possible in human
      granulomas, due to various confounding factors. Nonhuman Primates (NHPs) infected
      with Mtb accurately reflect human TB in clinical and pathological contexts.
      METHODOLOGY/PRINCIPAL FINDINGS: We studied transcriptomics of granuloma lesions
      in the lungs of NHPs exhibiting active TB, during early and late stages of
      infection. Early TB lesions were characterized by a highly pro-inflammatory
      environment, expressing high levels of immune signaling pathways involving
      IFNgamma, TNFalpha, JAK, STAT and C-C/C-X-C chemokines. Late TB lesions, while
      morphologically similar to the early ones, exhibited an overwhelming silencing of
      the inflammatory response. Reprogramming of the granuloma transcriptome was
      highly significant. The expression of approximately two-thirds of all genes
      induced in early lesions was later repressed. CONCLUSIONS/SIGNIFICANCE: The
      transcriptional characteristics of TB granulomas undergo drastic changes during
      the course of infection. The overwhelming reprogramming of the initial pro
      inflammatory surge in late lesions may be a host strategy to limit
      immunopathology. We propose that these host profiles can predict changes in
      bacterial replication and physiology, perhaps serving as markers for latency and
      reactivation.

PMID- 20824206
TI  - GOPred: GO molecular function prediction by combined classifiers.
AB  - Functional protein annotation is an important matter for in vivo and in silico
      biology. Several computational methods have been proposed that make use of a wide
      range of features such as motifs, domains, homology, structure and
      physicochemical properties. There is no single method that performs best in all
      functional classification problems because information obtained using any of
      these features depends on the function to be assigned to the protein. In this
      study, we portray a novel approach that combines different methods to better
      represent protein function. First, we formulated the function annotation problem
      as a classification problem defined on 300 different Gene Ontology (GO) terms
      from molecular function aspect. We presented a method to form positive and
      negative training examples while taking into account the directed acyclic graph
      (DAG) structure and evidence codes of GO. We applied three different methods and
      their combinations. Results show that combining different methods improves
      prediction accuracy in most cases. The proposed method, GOPred, is available as
      an online computational annotation tool (http://kinaz.fen.bilkent.edu.tr/gopred).

PMID- 20824207
TI  - Genome rearrangements detected by SNP microarrays in individuals with
      intellectual disability referred with possible Williams syndrome.
AB  - BACKGROUND: Intellectual disability (ID) affects 2-3% of the population and may
      occur with or without multiple congenital anomalies (MCA) or other medical
      conditions. Established genetic syndromes and visible chromosome abnormalities
      account for a substantial percentage of ID diagnoses, although for approximately
      50% the molecular etiology is unknown. Individuals with features suggestive of
      various syndromes but lacking their associated genetic anomalies pose a
      formidable clinical challenge. With the advent of microarray techniques,
      submicroscopic genome alterations not associated with known syndromes are
      emerging as a significant cause of ID and MCA. METHODOLOGY/PRINCIPAL FINDINGS:
      High-density SNP microarrays were used to determine genome wide copy number in 42
      individuals: 7 with confirmed alterations in the WS region but atypical clinical
      phenotypes, 31 with ID and/or MCA, and 4 controls. One individual from the first
      group had the most telomeric gene in the WS critical region deleted along with 2
      Mb of flanking sequence. A second person had the classic WS deletion and a
      rearrangement on chromosome 5p within the Cri du Chat syndrome (OMIM:123450)
      region. Six individuals from the ID/MCA group had large rearrangements (3
      deletions, 3 duplications), one of whom had a large inversion associated with a
      deletion that was not detected by the SNP arrays. CONCLUSIONS/SIGNIFICANCE:
      Combining SNP microarray analyses and qPCR allowed us to clone and sequence 21
      deletion breakpoints in individuals with atypical deletions in the WS region
      and/or ID or MCA. Comparison of these breakpoints to databases of genomic
      variation revealed that 52% occurred in regions harboring structural variants in
      the general population. For two probands the genomic alterations were flanked by
      segmental duplications, which frequently mediate recurrent genome rearrangements;
      these may represent new genomic disorders. While SNP arrays and related
      technologies can identify potentially pathogenic deletions and duplications,
      obtaining sequence information from the breakpoints frequently provides
      additional information.

PMID- 20824208
TI  - Specific responses of Salmonella enterica to tomato varieties and fruit ripeness
      identified by in vivo expression technology.
AB  - BACKGROUND: Recent outbreaks of vegetable-associated gastroenteritis suggest that
      enteric pathogens colonize, multiply and persist in plants for extended periods
      of time, eventually infecting people. Genetic and physiological pathways, by
      which enterics colonize plants, are still poorly understood.
      METHODOLOGY/PRINCIPAL FINDINGS: To better understand interactions between
      Salmonella enterica sv. Typhimurium and tomatoes, a gfp-tagged Salmonella
      promoter library was screened inside red ripe fruits. Fifty-one unique constructs
      that were potentially differentially regulated in tomato relative to in vitro
      growth were identified. The expression of a subset of these promoters was tested
      in planta using recombinase-based in vivo expression technology (RIVET) and
      fitness of the corresponding mutants was tested. Gene expression in Salmonella
      was affected by fruit maturity and tomato cultivar. A putative fadH promoter was
      upregulated most strongly in immature tomatoes. Expression of the fadH construct
      depended on the presence of linoleic acid, which is consistent with the reduced
      accumulation of this compound in mature tomato fruits. The cysB construct was
      activated in the fruit of cv. Hawaii 7997 (resistant to a race of Ralstonia
      solanacearum) more strongly than in the universally susceptible tomato cv. Bonny
      Best. Known Salmonella motility and animal virulence genes (hilA, flhDC, fliF and
      those encoded on the pSLT virulence plasmid) did not contribute significantly to
      fitness of the bacteria inside tomatoes, even though deletions of sirA and motA
      modestly increased fitness of Salmonella inside tomatoes.
      CONCLUSIONS/SIGNIFICANCE: This study reveals the genetic basis of the
      interactions of Salmonella with plant hosts. Salmonella relies on a distinct set
      of metabolic and regulatory genes, which are differentially regulated in planta
      in response to host genotype and fruit maturity. This enteric pathogen colonizes
      tissues of tomatoes differently than plant pathogens, and relies little on its
      animal virulence genes for persistence within the fruit.

PMID- 20824209
TI  - Identification of cis-regulatory elements in the mammalian genome: the cREMaG
      database.
AB  - BACKGROUND: A growing number of gene expression-profiling datasets provides a
      reliable source of information about gene co-expression. In silico analyses of
      the properties shared among the promoters of co-expressed genes facilitates the
      identification of transcription factors (TFs) involved in the co-regulation of
      those genes. Our previous experience with microarray data led to the development
      of a database suitable for the examination of regulatory motifs in the promoters
      of co-expressed genes. METHODOLOGY: We introduce the cREMaG (cis-Regulatory
      Elements in the Mammalian Genome) system designed for in silico studies of the
      promoter properties of co-regulated mammalian genes. The cREMaG system offers an
      analysis of data obtained from human, mouse, rat, bovine and canine gene
      expression-profiling studies. More than eight analysis parameters can be utilized
      in user-defined combinations. The selection of alternative transcription start
      sites and information about CpG islands are also available. CONCLUSIONS: Using
      the cREMaG system, we successfully identified TFs mediating transcriptional
      responses in reference gene sets. The cREMaG system facilitates in silico studies
      of mammalian transcriptional gene regulation. The resource is freely available at
      http://www.cremag.org.

PMID- 20824210
TI  - High-density genomewide linkage analysis of exceptional human longevity
      identifies multiple novel loci.
AB  - BACKGROUND: Human lifespan is approximately 25% heritable, and genetic factors
      may be particularly important for achieving exceptional longevity. Accordingly,
      siblings of centenarians have a dramatically higher probability of reaching
      extreme old age than the general population. METHODOLOGY/PRINCIPAL FINDINGS: To
      map the loci conferring a survival advantage, we performed the second genomewide
      linkage scan on human longevity and the first using a high-density marker panel
      of single nucleotide polymorphisms. By systematically testing a range of minimum
      age cutoffs in 279 families with multiple long-lived siblings, we identified a
      locus on chromosome 3p24-22 with a genomewide significant allele-sharing LOD
      score of 4.02 (empirical P = 0.037) and a locus on chromosome 9q31-34 with a
      highly suggestive LOD score of 3.89 (empirical P = 0.054). The empirical P value
      for the combined result was 0.002. A third novel locus with a LOD score of 4.05
      on chromosome 12q24 was detected in a subset of the data, and we also obtained
      modest evidence for a previously reported interval on chromosome 4q22-25.
      CONCLUSIONS/SIGNIFICANCE: Our linkage data should facilitate the discovery of
      both common and rare variants that determine genetic variability in lifespan.

PMID- 20824211
TI  - Psychometric evaluation of the altered states of consciousness rating scale
      (OAV).
AB  - BACKGROUND: The OAV questionnaire has been developed to integrate research on
      altered states of consciousness (ASC). It measures three primary and one
      secondary dimensions of ASC that are hypothesized to be invariant across ASC
      induction methods. The OAV rating scale has been in use for more than 20 years
      and applied internationally in a broad range of research fields, yet its
      factorial structure has never been tested by structural equation modeling
      techniques and its psychometric properties have never been examined in large
      samples of experimentally induced ASC. METHODOLOGY/PRINCIPAL FINDINGS: The
      present study conducted a psychometric evaluation of the OAV in a sample of
      psilocybin (n = 327), ketamine (n = 162), and MDMA (n = 102) induced ASC that was
      obtained by pooling data from 43 experimental studies. The factorial structure
      was examined by confirmatory factor analysis, exploratory structural equation
      modeling, hierarchical item clustering (ICLUST), and multiple indicators multiple
      causes (MIMIC) modeling. The originally proposed model did not fit the data well
      even if zero-constraints on non-target factor loadings and residual correlations
      were relaxed. Furthermore, ICLUST suggested that the "oceanic boundlessness" and
      "visionary restructuralization" factors could be combined on a high level of the
      construct hierarchy. However, because these factors were multidimensional, we
      extracted and examined 11 new lower order factors. MIMIC modeling indicated that
      these factors were highly measurement invariant across drugs, settings,
      questionnaire versions, and sexes. The new factors were also demonstrated to have
      improved homogeneities, satisfactory reliabilities, discriminant and convergent
      validities, and to differentiate well among the three drug groups.
      CONCLUSIONS/SIGNIFICANCE: The original scales of the OAV were shown to be
      multidimensional constructs. Eleven new lower order scales were constructed and
      demonstrated to have desirable psychometric properties. The new lower order
      scales are most likely better suited to assess drug induced ASC.

PMID- 20824212
TI  - Reporting of methodologic information on trial registries for quality assessment:
      a study of trial records retrieved from the WHO search portal.
AB  - BACKGROUND: Although randomized clinical trials (RCTs) are considered the gold
      standard of evidence, their reporting is often suboptimal. Trial registries have
      the potential to contribute important methodologic information for critical
      appraisal of study results. METHODS AND FINDINGS: The objective of the study was
      to evaluate the reporting of key methodologic study characteristics in trial
      registries. We identified a random sample (n = 265) of actively recruiting RCTs
      using the World Health Organization International Clinical Trials Registry
      Platform (ICTRP) search portal in 2008. We assessed the reporting of relevant
      domains from the Cochrane Collaboration's 'Risk of bias' tool and other key
      methodological aspects. Our primary outcomes were the proportion of registry
      records with adequate reporting of random sequence generation, allocation
      concealment, blinding, and trial outcomes. Two reviewers independently assessed
      each record. Weighted overall proportions in the ICTRP search portal for adequate
      reporting of sequence generation, allocation concealment, blinding (including and
      excluding open label RCT) and primary outcomes were 5.7% (95% CI 3.0-8.4%), 1.4%
      (0-2.8%), 41% (35-47%), 8.4% (4.1-13%), and 66% (60-72%), respectively. The
      proportion of adequately reported RCTs was higher for registries that used
      specific methodological fields for describing methods of randomization and
      allocation concealment compared to registries that did not. Concerning other key
      methodological aspects, weighted overall proportions of RCTs with adequately
      reported items were as follows: eligibility criteria (81%), secondary outcomes
      (46%), harm (5%) follow-up duration (62%), description of the interventions (53%)
      and sample size calculation (1%). CONCLUSIONS: Trial registries currently contain
      limited methodologic information about registered RCTs. In order to permit
      adequate critical appraisal of trial results reported in journals and registries,
      trial registries should consider requesting details on key RCT methods to
      complement journal publications. Full protocols remain the most comprehensive
      source of methodologic information and should be made publicly available.

PMID- 20824213
TI  - E-cadherin is required for centrosome and spindle orientation in Drosophila male
      germline stem cells.
AB  - Many adult stem cells reside in a special microenvironment known as the niche,
      where they receive essential signals that specify stem cell identity. Cell-cell
      adhesion mediated by cadherin and integrin plays a crucial role in maintaining
      stem cells within the niche. In Drosophila melanogaster, male germline stem cells
      (GSCs) are attached to niche component cells (i.e., the hub) via adherens
      junctions. The GSC centrosomes and spindle are oriented toward the hub-GSC
      junction, where E-cadherin-based adherens junctions are highly concentrated. For
      this reason, adherens junctions are thought to provide a polarity cue for GSCs to
      enable proper orientation of centrosomes and spindles, a critical step toward
      asymmetric stem cell division. However, understanding the role of E-cadherin in
      GSC polarity has been challenging, since GSCs carrying E-cadherin mutations are
      not maintained in the niche. Here, we tested whether E-cadherin is required for
      GSC polarity by expressing a dominant-negative form of E-cadherin. We found that
      E-cadherin is indeed required for polarizing GSCs toward the hub cells, an effect
      that may be mediated by Apc2. We also demonstrated that E-cadherin is required
      for the GSC centrosome orientation checkpoint, which prevents mitosis when
      centrosomes are not correctly oriented. We propose that E-cadherin orchestrates
      multiple aspects of stem cell behavior, including polarization of stem cells
      toward the stem cell-niche interface and adhesion of stem cells to the niche
      supporting cells.

PMID- 20824214
TI  - Ephrin-A5 and EphA5 interaction induces synaptogenesis during early hippocampal
      development.
AB  - BACKGROUND: Synaptogenesis is a fundamental step in neuronal development. For
      spiny glutamatergic synapses in hippocampus and cortex, synaptogenesis involves
      adhesion of pre and postsynaptic membranes, delivery and anchorage of pre and
      postsynaptic structures including scaffolds such as PSD-95 and NMDA and AMPA
      receptors, which are glutamate-gated ion channels, as well as the morphological
      maturation of spines. Although electrical activity-dependent mechanisms are
      established regulators of these processes, the mechanisms that function during
      early development, prior to the onset of electrical activity, are unclear. The
      Eph receptors and ephrins provide cell contact-dependent pathways that regulate
      axonal and dendritic development. Members of the ephrin-A family are glycosyl
      phosphatidylinositol-anchored to the cell surface and activate EphA receptors,
      which are receptor tyrosine kinases. METHODOLOGY/PRINCIPAL FINDINGS: Here we show
      that ephrin-A5 interaction with the EphA5 receptor following neuron-neuron
      contact during early development of hippocampus induces a complex program of
      synaptogenic events, including expression of functional synaptic NMDA receptor
      PSD-95 complexes plus morphological spine maturation and the emergence of
      electrical activity. The program depends upon voltage-sensitive calcium channel
      Ca2+ fluxes that activate PKA, CaMKII and PI3 kinase, leading to CREB
      phosphorylation and a synaptogenic program of gene expression. AMPA receptor
      subunits, their scaffolds and electrical activity are not induced. Strikingly, in
      contrast to wild type, stimulation of hippocampal slices from P6 EphA5 receptor
      functional knockout mice yielded no NMDA receptor currents.
      CONCLUSIONS/SIGNIFICANCE: These studies suggest that ephrin-A5 and EphA5 signals
      play a necessary, activity-independent role in the initiation of the early phases
      of synaptogenesis. The coordinated expression of the NMDAR and PSD-95 induced by
      eprhin-A5 interaction with EphA5 receptors may be the developmental switch that
      induces expression of AMPAR and their interacting proteins and the transition to
      activity-dependent synaptic regulation.

PMID- 20824215
TI  - Development of a chromosomally integrated metabolite-inducible Leu3p-alpha-IPM
      "off-on" gene switch.
AB  - BACKGROUND: Present technology uses mostly chimeric proteins as regulators and
      hormones or antibiotics as signals to induce spatial and temporal gene
      expression. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that a chromosomally
      integrated yeast 'Leu3p-alpha-IotaRhoMu' system constitutes a ligand-inducible
      regulatory "off-on" genetic switch with an extensively dynamic action area. We
      find that Leu3p acts as an active transcriptional repressor in the absence and as
      an activator in the presence of alpha-isopropylmalate (alpha-IotaRhoMu) in
      primary fibroblasts isolated from double transgenic mouse embryos bearing
      ubiquitously expressing Leu3p and a Leu3p regulated GFP reporter. In the absence
      of the branched amino acid biosynthetic pathway in animals, metabolically stable
      alpha-IPM presents an EC(50) equal to 0.8837 mM and fast "OFF-ON" kinetics
      (t(50)ON = 43 min, t(50)OFF = 2.18 h), it enters the cells via passive diffusion,
      while it is non-toxic to mammalian cells and to fertilized mouse eggs cultured ex
      vivo. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that the 'Leu3p-alpha
      IotaRhoMu' constitutes a simpler and safer system for inducible gene expression
      in biomedical applications.

PMID- 20824216
TI  - Osteopontin impairs host defense during established gram-negative sepsis caused
      by Burkholderia pseudomallei (melioidosis).
AB  - BACKGROUND: Melioidosis, caused by infection with Burkholderia (B.) pseudomallei,
      is a severe illness that is endemic in Southeast Asia. Osteopontin (OPN) is a
      phosphorylated glycoprotein that is involved in several immune responses
      including induction of T-helper 1 cytokines and recruitment of inflammatory
      cells. METHODOLOGY AND PRINCIPAL FINDINGS: OPN levels were determined in plasma
      from 33 melioidosis patients and 31 healthy controls, and in wild-type (WT) mice
      intranasally infected with B. pseudomallei. OPN function was studied in
      experimental murine melioidosis using WT and OPN knockout (KO) mice. Plasma OPN
      levels were elevated in patients with severe melioidosis, even more so in
      patients who went on to die. In patients who recovered plasma OPN concentrations
      had decreased after treatment. In experimental melioidosis in mice plasma and
      pulmonary OPN levels were also increased. Whereas WT and OPN KO mice were
      indistinguishable during the first 24 hours after infection, after 72 hours OPN
      KO mice demonstrated reduced bacterial numbers in their lungs, diminished
      pulmonary tissue injury, especially due to less necrosis, and decreased
      neutrophil infiltration. Moreover, OPN KO mice displayed a delayed mortality as
      compared to WT mice. OPN deficiency did not influence the induction of
      proinflammatory cytokines. CONCLUSIONS: These data suggest that sustained
      production of OPN impairs host defense during established septic melioidosis.

PMID- 20824218
TI  - Minocycline synergizes with N-acetylcysteine and improves cognition and memory
      following traumatic brain injury in rats.
AB  - BACKGROUND: There are no drugs presently available to treat traumatic brain
      injury (TBI). A variety of single drugs have failed clinical trials suggesting a
      role for drug combinations. Drug combinations acting synergistically often
      provide the greatest combination of potency and safety. The drugs examined
      (minocycline (MINO), N-acetylcysteine (NAC), simvastatin, cyclosporine A, and
      progesterone) had FDA-approval for uses other than TBI and limited brain injury
      in experimental TBI models. METHODOLOGY/PRINCIPAL FINDINGS: Drugs were dosed one
      hour after injury using the controlled cortical impact (CCI) TBI model in adult
      rats. One week later, drugs were tested for efficacy and drug combinations tested
      for synergy on a hierarchy of behavioral tests that included active place
      avoidance testing. As monotherapy, only MINO improved acquisition of the massed
      version of active place avoidance that required memory lasting less than two
      hours. MINO-treated animals, however, were impaired during the spaced version of
      the same avoidance task that required 24-hour memory retention. Co-administration
      of NAC with MINO synergistically improved spaced learning. Examination of brain
      histology 2 weeks after injury suggested that MINO plus NAC preserved white, but
      not grey matter, since lesion volume was unaffected, yet myelin loss was
      attenuated. When dosed 3 hours before injury, MINO plus NAC as single drugs had
      no effect on interleukin-1 formation; together they synergistically lowered
      interleukin-1 levels. This effect on interleukin-1 was not observed when the
      drugs were dosed one hour after injury. CONCLUSIONS/SIGNIFICANCE: These
      observations suggest a potentially valuable role for MINO plus NAC to treat TBI.

PMID- 20824217
TI  - Coronary microvascular disease in chronic Chagas cardiomyopathy including an
      overview on history, pathology, and other proposed pathogenic mechanisms.
AB  - This review focuses on the short and bewildered history of Brazilian scientist
      Carlos Chagas's discovery and subsequent developments, the anatomopathological
      features of chronic Chagas cardiomyopathy (CCC), an overview on the controversies
      surrounding theories concerning its pathogenesis, and studies that support the
      microvascular hypothesis to further explain the pathological features and
      clinical course of CCC. It is our belief that knowledge of this particular and
      remarkable cardiomyopathy will shed light not only on the microvascular
      involvement of its pathogenesis, but also on the pathogenetic processes of other
      cardiomyopathies, which will hopefully provide a better understanding of the
      various changes that may lead to an end-stage heart disease with similar
      features. This review is written to celebrate the 100th anniversary of the
      discovery of Chagas disease.

PMID- 20824219
TI  - Metabolic changes reveal the development of schistosomiasis in mice.
AB  - Schistosomiasis is a parasitic zoonosis caused by small trematode worms called
      schistosomes, amongst which Schistosoma japonicum (S. japonicum) is endemic in
      Asia. In order to understand the schistosome-induced changes in the host
      metabolism so as to facilitate early diagnosis of schistosomiasis, we
      systematically investigated the dynamic metabolic responses of mice biofluids and
      liver tissues to S. japonicum infection for five weeks using (1)H NMR
      spectroscopy in conjunction with multivariate data analysis. We were able to
      detect schistosomiasis at the third week post-infection, which was one week
      earlier than "gold standard" methods. We found that S. japonicum infection caused
      significant elevation of urinary 3-ureidopropionate, a uracil catabolic product,
      and disturbance of lipid metabolism, stimulation of glycolysis, depression of
      tricarboxylic acid cycle and disruption of gut microbiota regulations. We further
      found that the changes of 3-ureidopropionate and overall metabolic changes in
      both urinary and plasma samples were closely correlated with the time-course of
      disease progression. Furthermore, such changes together with liver tissue
      metabonome were clearly associated with the worm-burdens. These findings provided
      more insightful understandings of host biological responses to the infection and
      demonstrated that metabonomic analysis is potentially useful for early detection
      of schistosomiasis and comprehension of the mechanistic aspects of disease
      progression.

PMID- 20824221
TI  - PURLs: Another option for patients with liver disease.
AB  - Currently used to treat hepatic encephalopathy, rifaximin is effective at
      preventing this common complication of chronic liver disease, as well.

PMID- 20824222
TI  - What's a med school to do?

PMID- 20824220
TI  - Comparative genomic analysis of pathogenic and probiotic Enterococcus faecalis
      isolates, and their transcriptional responses to growth in human urine.
AB  - Urinary tract infection (UTI) is the most common infection caused by enterococci,
      and Enterococcus faecalis accounts for the majority of enterococcal infections.
      Although a number of virulence related traits have been established, no
      comprehensive genomic or transcriptomic studies have been conducted to
      investigate how to distinguish pathogenic from non-pathogenic E. faecalis in
      their ability to cause UTI. In order to identify potential genetic traits or gene
      regulatory features that distinguish pathogenic from non-pathogenic E. faecalis
      with respect to UTI, we have performed comparative genomic analysis, and
      investigated growth capacity and transcriptome profiling in human urine in vitro.
      Six strains of different origins were cultivated and all grew readily in human
      urine. The three strains chosen for transcriptional analysis showed an overall
      similar response with respect to energy and nitrogen metabolism, stress
      mechanism, cell envelope modifications, and trace metal acquisition. Our results
      suggest that citrate and aspartate are significant for growth of E. faecalis in
      human urine, and manganese appear to be a limiting factor. The majority of
      virulence factors were either not differentially regulated or down-regulated.
      Notably, a significant up-regulation of genes involved in biofilm formation was
      observed. Strains from different origins have similar capacity to grow in human
      urine. The overall similar transcriptional responses between the two pathogenic
      and the probiotic strain suggest that the pathogenic potential of a certain E.
      faecalis strain may to a great extent be determined by presence of fitness and
      virulence factors, rather than the level of expression of such traits.

PMID- 20824223
TI  - Bariatric society is here to help.
AB  - Most primary care physicians do not have the time, knowledge, or training to
      assist their obese patients with weight loss. I would like to suggest that
      physicians refer their patients to a medical bariatric physician in order to
      properly address obesity and its related comorbidities.

PMID- 20824224
TI  - FP's patients are successful "losers".
AB  - The more people we help to make healthier, the less money will be needed to
      provide care for people who are sick.

PMID- 20824225
TI  - How best to manage treatment-resistant depression?
AB  - Should you augment the treatment regimen with lithium, thyroxin, or an atypical
      antipsychotic? This review will help you decide.

PMID- 20824226
TI  - Sued for misdiagnosis? It could happen to you.
AB  - Plaintiffs' attorneys and patient safety advocates alike are increasingly
      focusing their attention on diagnostic errors. Here are the key pitfalls and ways
      to avoid them.

PMID- 20824227
TI  - When to suspect atypical cystic fibrosis.
AB  - Not all patients with cystic fibrosis have abnormal sweat chloride levels, severe
      lung disease, or failure to thrive. These 2 cases remind us to think "outside the
      box".

PMID- 20824228
TI  - Flu season's almost here: Are you ready?
AB  - This year, a single vaccine includes the 2009 H1N1 and 2 other strains and most
      of your patients will need only 1 dose. The public health goal: Immunize everyone
      without a contraindication.

PMID- 20824229
TI  - Bluish pigmentation of face and sclera.
AB  - Was this a case of Addison's disease, hemochromatosis, or melanoma? Or did one of
      the patient's medications have something to do with it?

PMID- 20824230
TI  - Clinical Inquiries: Which drugs should post-MI patients routinely receive?
AB  - Patients should be placed on the following medications: antiplatelet agents,
      (meta-analysis for aspirin, multiple randomized controlled trials [RCTs] for
      aspirin plus clopidogrel); a statin; atorvastatin has the best evidence (a single
      RCT); a beta-blocker (meta-analysis); renin-angiotensin-aldosterone system
      blockers, whether or not the ejection fraction is diminished after myocardial
      infarction (MI) (SOR: A, meta-analysis for angiotensin-converting enzyme [ACE]
      inhibitor; B, single RCT for ACE inhibitor plus aldosterone blocker).

PMID- 20824231
TI  - Clinical Inquiries: Does exercise alleviate symptoms of depression?
AB  - Yes. Exercise reduces patient-perceived symptoms of depression when used as
      monotherapy (strength of recommendation [SOR]: B, meta-analysis of randomized
      controlled trials [RCTs] with significant heterogeneity). It relieves symptoms as
      effectively as cognitive behavioral therapy (CBT) or pharmacologic anti
      depressant therapy (SOR: B, meta-analysis) and more effectively than bright light
      therapy (SOR: B, meta-analysis). Resistance exercise and mixed exercise
      (resistance and aerobic) work better than aerobic exercise alone (SOR: B, meta
      analysis). High-frequency exercise is more effective than low-frequency exercise
      (SOR: B, small RCT). "Mindful" exercise, which has a meditative focus, such as
      tai chi and yoga, also reduces symptoms of depression (SOR: B, systematic review
      of RCTs).

PMID- 20824232
TI  - Clinical Inquiries: How can we keep impaired glucose tolerance and impaired
      fasting glucose from progressing to diabetes?
AB  - Lifestyle changes and some drugs can help. Lifestyle interventions aimed at
      weight loss of 5% to 10% of body weight along with moderate aerobic exercise such
      as brisk walking for 150 minutes a week are the most effective means to prevent
      impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) from
      progressing to diabetes (strength of recommendation [SOR]: A, several meta
      analyses, including a recent Cochrane review).

PMID- 20824233
TI  - Clinical Inquiries: What is the best noninvasive diagnostic test for women with
      suspected CAD?
AB  - Multidetector computed tomography (MDCT) may be the most sensitive and specific
      noninvasive diagnostic test for women with suspected coronary artery disease
      (CAD) (strength of recommendation [SOR]: A, multiple prospective cohort studies).
      However, stress echocardiography and nuclear medicine perfusion testing are still
      the best well-tested and readily available alternatives in light of the newness
      of MDCT and concerns regarding its use (SOR: A, meta-analysis and cohort
      studies). Standard exercise treadmill testing (ETT) doesn't adequately exclude or
      confirm CAD in women (SOR: A, multiple prospective cohort studies).

PMID- 20824235
TI  - Distinguishing among incretin-based therapies. Glucose-lowering effects of
      incretin-based therapies.
AB  - Extensive experience from randomized clinical trials demonstrates the efficacy of
      GLP-1 agonists and DPP-4 inhibitors as monotherapy and in combination with
      metformin and other agents, although reductions in FPG and PPG, and consequently
      A1C, are greater with GLP-1 agonists than with DPP-4 inhibitors. This difference
      may result from the pharmacologic levels of GLP-1 activity that are achieved with
      the GLP-1 agonists and their direct action on the GLP-1 receptor. The GLP-1
      agonists have attributes that would make either of them an appropriate choice in
      the management of all 3 patients in our case studies, while either DPP-4
      inhibitor would be an appropriate choice for Case 1. Differences in dosing,
      administration, safety, and tolerability should be considered.

PMID- 20824236
TI  - Distinguishing among incretin-based therapies. Safety, tolerability, and
      nonglycemic effects of incretin-based therapies.
AB  - The overall safety profiles of GLP-1 agonists and DPP-4 inhibitors are favorable,
      with a low incidence of hypoglycemia. This attribute, along with their weight and
      cardiovascular benefits, particularly with the GLP-1 agonists, make them
      appropriate choices in our 3 patient cases. Ongoing safety investigations with
      GLP-1 agonists and DPP-4 inhibitors will provide further clarity to the complete
      safety profiles of these agents.

PMID- 20824237
TI  - Distinguishing among incretin-based therapies. Patient education and self
      management.
AB  - Working closely with patients and providing ongoing education, ideally in
      conjunction with a diabetes care team, can help ensure that the best treatment
      options are selected for an individual patient and that the patient is capable of
      effective self-management.

PMID- 20824238
TI  - Distinguishing among incretin-based therapies. Introduction.
AB  - The "treat to target" approach is to quickly achieve the target glycosylated
      hemoglobin (AIC) goal of <7% in most people, and then intensify or change therapy
      as needed to maintain glycemic control. Results of an online survey demonstrate
      uncertainty regarding the clinical differences between glucagon-like peptide (GLP
      1) agonists and dipeptidyl peptidase (DPP)-4 inhibitors. The increasingly
      important roles of the GLP-1 agonists and DPP-4 inhibitors stem from their
      overall good efficacy and safety profiles compared with other treatment options.

PMID- 20824239
TI  - Distinguishing among incretin-based therapies. Pathophysiology of type 2 diabetes
      mellitus: potential role of incretin-based therapies.
AB  - The multifactorial nature of the pathogenesis of T2DM provides an opportunity to
      combine treatments that act upon different mechanisms. In addition to improving
      insulin resistance and pancreatic beta-cell dysfunction, the GLP-1 agonists and
      DPP-4 inhibitors improve the impaired incretin response, as well as increase
      insulin secretion and reduce glucagon secretion, both in a glucose-dependent
      manner. As a result of these multiple actions, the GLP-1 agonists and DPP-4
      inhibitors lower both fasting and postprandial glucose levels. The effects of GLP
      1 agonists tend to be greater, probably because they produce pharmacologic levels
      of GLP-1 compared to physiologic levels with the DPP-4 inhibitors. Another
      difference is that unlike the DPP-4 inhibitors, the GLP-1 agonists also slow
      gastric emptying and promote satiety.

PMID- 20824240
TI  - Protect your patients, protect your practice: practical risk assessment in the
      structuring of opioid therapy in chronic pain.

PMID- 20824241
TI  - Photochemical behavior of (diphosphine)(eta(2)-tolane)Pt(0) complexes. Part A:
      Experimental considerations in solution and in the solid state.
AB  - A series of various (diphosphine)(eta(2)-tolane)Pt(0) complexes exhibiting
      manifold substitution pattern of the tolane ligand (5a-g) and different rigid
      diphosphines defining various bite angles at the Pt center (9a-b) have been
      synthesized. All compounds were isolated and characterized by means of
      spectroscopic methods and additionally by X-ray structure determination (5a-e, 9a
      b). In view of potential C(aryl)-C(ethynyl) bond activation, we investigated
      their photochemical behavior in the solid state as well as in solution by
      irradiating with sunlight. The reactivity towards C(aryl)-C(ethynyl) bond
      activation in the crystalline state and in solution is discussed in relation to
      substituents attached to the tolane ligand and on the extent of the torsion of
      its phenyl rings. Complexes 5a-c and 9a either bearing electron withdrawing
      bromides or possessing a large dihedral angle of the phenyl rings, showed
      selective oxidative addition of the C(aryl)-C(ethynyl) bond to the Pt center in
      the solid state, yielding complexes 6a-c and 10a, respectively. In contrast, 5d-f
      and 9b proved to be unreactive under similar conditions because of their electron
      donating methoxy groups as well as the reduced twisting of their phenyl or
      pyridyl moieties of the tolane ligands. Irradiation of complexes 5a and 5b with
      sunlight in solution revealed the formation of the appropriate C-Br activated
      compounds 7a and 7b along with 6a and 6b in a 1 : 1 mixture. The observed
      photochemical C(aryl)-C(ethynyl) bond activation is reversible under thermal
      conditions, regaining the appropriate Pt(0) complexes by reductive elimination.

PMID- 20824247
TI  - Single-molecule, single-particle fluorescence imaging of TiO2-based
      photocatalytic reactions.
AB  - Nanostructured metal oxide semiconductors, such as TiO(2) and ZnO, have attracted
      great attention as the promising material for photovoltaic devices,
      photocatalysts for water splitting and environmental purification, sensors,
      batteries, etc. In this critical review, we have focused on the on-site
      observation of interfacial chemical reactions involving charge carriers and
      reactive oxygen species (ROS), such as singlet oxygen and the hydroxyl radical,
      generated by the photoexcitation of TiO(2) nanoparticles using single-molecule,
      single-particle fluorescence spectroscopy. Advanced fluorescence imaging
      techniques enable us to determine the location of the photocatalytically active
      sites that are closely related to the defects heterogeneously distributed on the
      surface. Consequently, this review provides a great opportunity to understand the
      temporal and spatial heterogeneities within an individual catalyst particle,
      allowing for the potential use of single-molecule, single-particle approaches in
      the analysis of photocatalytic reactions (189 references).

PMID- 20824253
TI  - Unexpected dissociation energetics of the Na(+) counterion from GC motifs in DNA
      hole-migration.
AB  - We present here a theoretical investigation of the electronic and energetic
      properties of Na(+)GC, a DNA motif bound to a sodium ion (Na(+)) at the N(7) and
      O(6) sites of guanine (G), and its hole-trapped derivative [Na(+)GC](+) using
      density functional theory calculations. Normally, Na(+)GC has positive
      dissociation energies along various dissociation channels. However, hole-trapping
      of the Na(+)GC motif can lead to an unusual energetic phenomenon. Hole-trapping
      can reduce not only the dissociation barrier by destabilizing the Na(+)GC motif
      to a metastable state, but also the dissociation energy of the Na(+)N(7)/O(6)
      bond with an unexpected change from a positive to a negative value (61.51 versus
      16.18 kcal mol(-1)). This unexpected negative dissociation energy phenomenon
      implies that this motif can store energy (~16 kcal mol(-1)) in the Na(+)N(7)/O(6)
      bond zone due to hole-trapping. The topological properties of electron densities
      and the Laplacian values at the bond critical points indicate that this energetic
      phenomenon mainly originates from additional electrostatic repulsions between two
      moieties linked via a high-energy bond (Na(+)N(7)/O(6)). Proton transfer from G
      induced by hole-trapping can expand the negative dissociation energy zone to both
      Na(+)N(7)/O(6) and Watson-Crick (WC) H-bond zones. Similar phenomena can be
      observed for the Na(+) binding at the minor groove. Solvation of the hole-trapped
      Na(+)GC motif can change the negative dissociation energies by varying degrees,
      depending on the solvent-binding sites and the polarity of the solvents.

PMID- 20824254
TI  - Application of the additivity of group energies to understand conformational
      preference: the anomeric effect.
AB  - The conformational preference in normal and reverse anomeric effects is analyzed
      by taking advantage of the known additivity and transferability of functional
      group energies defined by the gradient of the electron density. As the anomeric
      effect has an energetic origin and every change in the electron density produces
      an energetic change, an explanation of this phenomenon should be based on the
      density changes taking place in a conformational equilibrium. The total energy of
      substituted cyclohexanoids is partitioned into ring and substituent contributions
      and the preferred conformation is the result of a balance between them. This new
      alternative approach allows understanding of the anomeric effect in terms of
      group energy contributions. In general, the most stable conformer in both the
      anomeric and reverse anomeric effects is that where the ring transfers charge to
      the heteroatom in the substituent during the process.

PMID- 20824255
TI  - Non-contact fluorescent bleaching-independent method for temperature measurement
      in microfluidic systems based on DNA melting curves.
AB  - This report introduces a bleaching-independent temperature measurement method
      based on the analysis of the fluorescence emitted during the melting of DNA
      molecules with the SYBR-Green I intercalator, in a microvolume where the strong
      non-linearity of the signal is used to eliminate the photobleaching effect as
      well as to determine the heat transfer rate between a heater and the sample and
      the temperature non-uniformity within the sample.

PMID- 20824256
TI  - Greatly enhanced binding of a cationic porphyrin towards bovine serum albumin by
      cucurbit[8]uril.
AB  - Binding affinity towards serum albumin and intracellular proteins is of
      importance for a photodynamic therapy (PDT) sensitizer to selectively localize in
      tumours and efficiently induce cell death. In this paper, it was found that
      cucurbit[8]uril (CB8) can greatly improve the binding affinity of 5,10,15,20
      tetrakis(1-methyl-4-pyridinio)porphyrin tetra(p-toluenesulfonate) (TMPyP), a
      promising PDT photosensitizer, towards bovine serum albumin (BSA). Absorption,
      fluorescence emission, (1)H NMR, dynamic light scattering, atomic force
      microscope, as well as protein photocleavage measurements suggest that the
      binding enhancement originates from the formation of a ternary complex of
      CB8.TMPyP.tryptophan residues. This finding opens up a new approach for the
      development of more efficient PDT agents.

PMID- 20824257
TI  - Charge transport and diffusion of ionic liquids in nanoporous silica membranes.
AB  - Charge transport in 1-hexyl-3-methylimidazolium hexafluorophosphate ionic liquid
      in oxidized nanoporous silicon membranes is investigated in a wide frequency and
      temperature range by a combination of Broadband Dielectric Spectroscopy (BDS) and
      Pulsed Field Gradient Nuclear Magnetic Resonance (PFG NMR). By applying the
      Einstein-Smoluchowski relations to the dielectric spectra, diffusion coefficient
      is obtained in quantitative agreement with independent PFG NMR measurements. More
      than 10-fold systematic decrease in the effective diffusion coefficient from the
      bulk value is observed in hydrophilic silica nanopores. A model assuming a
      reduced mobility at the pore-matrix interface is shown to provide a quantitative
      explanation for the remarkable decrease of effective transport quantities (such
      as diffusion coefficient, dc conductivity and consequently, the dielectric loss)
      of the ionic liquid in non-silanized membranes. This approach is supported by the
      observation that silanization of porous silica membranes results in a significant
      increase of the effective diffusion coefficient, which approaches the value for
      the bulk liquid.

PMID- 20824263
TI  - [Successful symptomatic treatment of epidermodysplasia verruciformis with
      imiquimod 5% cream].
AB  - A 19-year-old patient presented with epidermodysplasia verruciformis (EV). In
      this genodermatosis, pathogenetic factors such as infection by human papilloma
      viruses as well as sun exposure are considered responsible for the malignant
      transformation of EV lesions to skin cancer within decades. So far, several
      therapeutic strategies have been unsatisfactory. In our case HPV 5b was detected
      and the associated skin lesions were successfully treated with imiquimod 5%
      cream.

PMID- 20824264
TI  - Role of mitofusin 2 in cardiovascular oxidative injury.
AB  - Mitochondria are highly dynamic organelles with constant shape changes regulated
      by fusion and fission events. In addition to regulating mitochondrial morphology,
      mitochondrial fusion/fission is involved in fundamental mitochondrial biological
      processes, including mitochondrial metabolism, energization, respiration,
      mitochondrial membrane potential, and mtDNA stability. Dysfunction of
      mitochondrial dynamics has been implicated in various human diseases, especially
      in neurodegenerative diseases. Emerging evidence indicates that impaired
      expression of mitochondrial fusion proteins or their malfunction participates in
      oxidative stress-induced cardiovascular injury. This review will focus on recent
      advances of mitochondrial fusion in regulating various cellular processes in
      cardiovascular system.

PMID- 20824265
TI  - [Hand surgery in traumatology].

PMID- 20824266
TI  - [Endourological lithotripsy for stone removal: accidental fragmentation of dormia
      basket and guidewire - a brief overview].
AB  - Endoscopic lithotripsy of stones is one of the most frequently performed
      procedures in urology. Sometimes dormia baskets and guidewire will be fragmented
      accidentally by the laser (Hol:YAG), by ultrasound, or by mechanical lithotripsy
      (electromechanical or pneumatic).A search for articles on this subject was
      performed. The aim of this article is to provide a review about the literature on
      this subject and how this subject can be managed. In this article we describe the
      energy needed for destroying specific foreign bodies and what currently and in
      the future will be the best way to avoid this problem.

PMID- 20824267
TI  - [Online support groups for localized prostate cancer: qualitative analysis of
      decision making].
AB  - BACKGROUND: In localized prostate cancer individual treatment decisions cannot be
      reached relying exclusively on medical data. Therefore, social interaction is of
      considerable importance and online support groups allow us to get to know a facet
      of this communication. MATERIAL AND METHODS: We investigated 82 thematically
      relevant threads representing 5% of the largest German online support group on
      prostate cancer (http://forum.prostatakrebs-bps.de). Two independent
      investigators used methods derived from grounded theory and linguistic
      conversation analysis to characterize the sample. RESULTS: Users report on
      personal experience and provide subjective recommendations. At the same time
      those seeking advice are encouraged to weigh the information and to decide for
      themselves. Some urologists contribute to the discussion and seem to have a
      corrective influence, but their involvement is judged diversely. As mainly lay
      people with different levels of knowledge are involved in the discussion, a
      tentative language style is frequently used. The disease itself appears to be a
      linguistic taboo. Besides treatment recommendations, emotional support is of
      major concern. Being personally affected establishes a sense of unity, which adds
      to the subjective value of the communication. CONCLUSIONS: Patients readily
      receive information, advice and emotional support in online support groups.
      Knowledge of such online services is useful in ensuring good counselling for our
      patients.

PMID- 20824268
TI  - [Perioperative antocoagulation in patients with prosthetic heart valves:
      recommendations].
AB  - Lifelong anticoagulation, mainly with oral Vitamin K antagonists, represents the
      treatment of choice in patients with prosthetic heart valves to prevent
      thrombembolic complications. As a result, anticoagulant-related complications
      like excessive bleeding during interventions or surgical procedures will occur.
      Therefore, timely stopping of vitamin K antagonists prior to elective surgery is
      mandatory. However, based on the long half-life of all common vitamin K
      antagonists, interruption of oral anticoagulation will definitively lead to an
      increase of thrombembolic events. Hence, adequate bridging anticoagulation by
      temporary substitution of this therapy with heparin is necessary. This article
      gives a recommendation on the basis of the American College of Chest Physician
      and European Society of Cardiology current.

PMID- 20824269
TI  - Clinical and structural evaluation of arthroscopic double-row suture-bridge
      rotator cuff repair: early results of a novel technique.
AB  - PURPOSE: Assessment of repair integrity and clinical outcome after arthroscopic
      repair of rotator cuff tears in double-row suture-bridge technique with the use
      of a new knotless suture-anchor system. METHODS: The first treated 25 patients
      with arthroscopic rotator cuff repair in the suture-bridge technique using a
      novel knotless anchor and chain-link suture system were evaluated. Patients with
      isolated full-thickness supraspinatus tears were selected. They were followed
      clinically with functional scores (Constant score, ASES index), visual analog
      scale (VAS), and instrumentally with Isobex digital strength analyzer
      preoperatively, at 6 and 14 months postoperatively. The repair integrity was
      evaluated with MRI at an average of 14 months postoperatively. RESULTS:
      Significant improvement of pain, strength, range of motion, and functional scores
      occurred (P < 0.05). There was a re-tear rate of 20%. The subjective parameters
      (VAS and ASES Index) showed non-significant (n.s.) differences between the re
      tear and intact repair groups, whereas the objective parameters (Constant score,
      muscle power and active ROM) showed significant differences between both groups
      (P < 0.05). CONCLUSION: The functional outcome has improved significantly with
      this new knotless anchor-chain system and was more superior in shoulders with
      intact repair, whereas the resulted repair integrity was not better than other
      types of double-row repair techniques mentioned in the recent literature.
      However, this early report of the novel technique may show limited power for
      comparison due to the relatively small sample size.

PMID- 20824271
TI  - Inseparable thoraco-omphalopagus twins.
AB  - Conjoined twins occur at the rate of 1 in 50 to 200,000 live births, and 75% of
      these share the thorax (thoracopagus) or the thorax and upper abdomen (thoraco
      omphalopagus), resulting in cardiac and hepatic sharing. Antenatal diagnosis can
      delineate the cardiac anatomy and provide parental counseling on whether
      separation is possible after birth. In the majority of cases, thoracopagus twins
      have a complex cardiac anatomy and share a common pericardial sac. Separation and
      survival depend on the extent to which the cardiac chambers and conduction system
      are fused. When the twins share the atria, ventricles, or both, death is
      inevitable even if surgical separation is occasionally attempted.

PMID- 20824270
TI  - Efficacy and tolerability of high-dose dronabinol maintenance in HIV-positive
      marijuana smokers: a controlled laboratory study.
AB  - RATIONALE: Dronabinol (Delta(9)tetrahydrocannabinol) is approved for HIV-related
      anorexia, yet, little is known about its effects in HIV-positive marijuana
      smokers. HIV-negative marijuana smokers require higher than recommended
      dronabinol doses to experience expected effects. OBJECTIVES: Employing a within
      subjects, double-blind, placebo-controlled design, we assessed the effects of
      repeated high-dose dronabinol in HIV-positive marijuana smokers taking
      antiretroviral medication. METHODS: Participants (N = 7), who smoked marijuana
      4.2 +/- 2.3 days/week, resided in a residential laboratory for two 16-day stays,
      receiving dronabinol (10 mg QID) in one stay and placebo in the other. Efficacy
      was assessed with objectively verified food intake and body weight. Tolerability
      was measured with sleep, subjective, and cognitive assessments. For analyses,
      each inpatient stay was divided into two phases, days 1-8 and 9-16; we compared
      dronabinol's effects with placebo in each 8-day phase to investigate tolerance.
      RESULTS: Despite sustained increases in self-reported food cravings, dronabinol
      only increased caloric intake in the initial 8 days of dosing. Similarly, sleep
      quality was improved only in the first 8 days of dosing. Dronabinol's mood
      enhancing effects were sustained across the 16-day inpatient stay. Dronabinol was
      well tolerated, causing few negative subjective or cognitive effects.
      CONCLUSIONS: In HIV-positive marijuana smokers, high dronabinol doses safely and
      effectively increased caloric intake. However, repeated high-dose dronabinol
      appeared to result in selective tolerance to these effects. These findings
      indicate that HIV-positive individuals who smoke marijuana may require higher
      dronabinol doses than are recommended by the FDA. Future research to establish
      optimal dosing regimens, and reduce the development of tolerance, is required.

PMID- 20824272
TI  - FRET characterisation for cross-bridge dynamics in single-skinned rigor muscle
      fibres.
AB  - In this work we demonstrate for the first time the use of Forster resonance
      energy transfer (FRET) as an assay to monitor the dynamics of cross-bridge
      conformational changes directly in single muscle fibres. The advantage of FRET
      imaging is its ability to measure distances in the nanometre range, relevant for
      structural changes in actomyosin cross-bridges. To reach this goal we have used
      several FRET couples to investigate different locations in the actomyosin
      complex. We exchanged the native essential light chain of myosin with a
      recombinant essential light chain labelled with various thiol-reactive
      chromophores. The second fluorophore of the FRET couple was introduced by three
      approaches: labelling actin, labelling SH1 cysteine and binding an adenosine
      triphosphate (ATP) analogue. We characterise FRET in rigor cross-bridges: in this
      condition muscle fibres are well described by a single FRET population model
      which allows us to evaluate the true FRET efficiency for a single couple and the
      consequent donor-acceptor distance. The results obtained are in good agreement
      with the distances expected from crystallographic data. The FRET characterisation
      presented herein is essential before moving onto dynamic measurements, as the
      FRET efficiency differences to be detected in an active muscle fibre are on the
      order of 10-15% of the FRET efficiencies evaluated here. This means that, to
      obtain reliable results to monitor the dynamics of cross-bridge conformational
      changes, we had to fully characterise the system in a steady-state condition,
      demonstrating firstly the possibility to detect FRET and secondly the viability
      of the present approach to distinguish small FRET variations.

PMID- 20824273
TI  - Changing approaches to cholecystectomy in elderly patients: a 10-year
      retrospective study in Taiwan.
AB  - BACKGROUND: The prevalence of symptomatic gallbladder diseases increases with
      age. The present study evaluated cholecystectomy risk factors and hospital
      resource utilization in an elderly (aged 60 years and older) population of
      patients who had undergone open cholecystectomy (OC) or laparoscopic
      cholecystectomy (LC). METHODS: The study analyzed 20,538 OC and 29,318 LC
      procedures performed in Taiwan from 1996 to 2007. Odds ratio (OR) and 95%
      confidence interval were calculated to assess the relative change rate.
      Regression models were employed to predict length of stay (LOS) and total
      surgical cost. RESULTS: Patient characteristics associated with increased
      likelihood of undergoing LC were age 60-69 years, female gender, and lack of
      current co-morbidities. Length of stay associated with both OC and LC decreased
      during the study period. Total surgical cost for elderly OC patients increased
      during the study period, whereas that for elderly LC patients declined. Compared
      to OC patients, LC patients had significantly larger changes in LOS (-2.27 days)
      and total surgical cost ($ -368.64 U.S. dollars) (p < 0.001). The following
      factors were associated with considerable increases in both LOS and total
      surgical cost: advanced age, female gender, presence of one or more co
      morbidities, treatment in a regional or a district hospital, and long LOS.
      CONCLUSIONS: Decreases in hospital resource utilization were larger in elderly LC
      patients than in elderly OC patients. Health care providers and patients should
      observe that hospital resource utilization may depend on hospital attributes as
      well as patient attributes. These analytical results should be applicable to
      similar elderly populations in other countries.

PMID- 20824274
TI  - Prognostic impact of extrathyroid extension and clinical lymph node metastasis in
      papillary thyroid carcinoma depend on carcinoma size.
AB  - BACKGROUND: Although papillary thyroid carcinoma (PTC) generally has an indolent
      nature, massive extrathyroid extension (Ex) and clinical lateral node metastasis
      (N1b) are prominent predictors of a dire prognosis. However, it remains unknown
      whether these factors affect patient prognosis with uniformity. In this study, we
      investigated the relationships between the prognostic impact of these factors and
      carcinoma size. METHODS: A total of 5,917 patients who underwent initial and
      curative surgery for PTC between 1987 and 1995 were enrolled in this study. After
      dividing these patients into four subsets based on tumor size--?1.0 cm, 1.1-2.0
      cm, 2.1-3.0 cm, and >3.0 cm--we investigated the prognostic impacts of Ex and N1b
      in each subset. RESULTS: Relative risk (RR) of disease-free survival (DFS) of N1b
      was the highest in the subset ?1.0 cm and decreased with tumor size. RR of Ex was
      smaller in carcinoma ?3.0 cm but larger in carcinoma >3.0 cm compared with that
      of N1b in the respective subsets. On multivariate analysis, N1b was a more
      important prognostic factor than Ex in carcinoma ?3.0 cm, but the prognostic
      impacts of these two factors were reversed in carcinoma >3.0 cm. Similar findings
      were obtained in analyses for cause-specific survival (CSS) and prognostic value
      of N1b was more significant in carcinoma ?3.0 cm but less significant in
      carcinoma >3.0 cm than that of Ex. CONCLUSIONS: The prognostic values of Ex and
      N1b vary with tumor size in PTC. It is important for physicians to pay attention
      to tumor size when evaluating the prognostic impact of these two prominent
      factors.

PMID- 20824275
TI  - Anti-VEGF with 3-week intervals is effective on anemia in a patient with severe
      hereditary hemorrhagic telangiectasia.

PMID- 20824276
TI  - Assessment of the mobilizable vector plasmids pSUP202 and pSUP404.2 as genetic
      tools for the predatory bacterium Bdellovibrio bacteriovorus.
AB  - Bdellovibrio and like organisms (BALOs) form the group of predatory bacteria
      which require Gram-negative bacteria as prey. Genetic studies with Bdellovibrio
      bacteriovorus can be performed with vectors which are introduced into the
      predator via conjugation. The usefulness of the two vectors pSUP202 and pSUP404.2
      as genetic tools were assessed. Both vectors were transferable into B.
      bacteriovorus by conjugative matings with an Escherichia coli K12 strain as
      donor. The transfer frequency was higher for vector pSUP404.2 (approx. 10-1-10-4)
      as for pSUP202 (approx. 10-5-10-6). Vector pSUP202 with a pMB1 origin is unstable
      in the predatory bacterium, whereas pSUP404.2 is stably maintained in the absence
      of selective antibiotics. pSUP404.2 harbors two plasmid replicons, the p15A ori
      and the RSF1010 replication region The copy number of pSUP404.2 was determined by
      quantitative PCR in B. bacteriovorus and averages seven copies per genome.
      pSUP404.2 harbors two resistance genes (chloramphenicol and kanamycin) which can
      be used for cloning either by selection for transconjugants or by insertional
      inactivation.

PMID- 20824277
TI  - Comparative proteomic analyses of Streptococcus suis serotype 2 cell wall
      associated proteins.
AB  - Streptococcus suis serotype 2 (SS2) is a zoonotic pathogen that is distributed
      throughout the world. Virulence factors and/or markers of the virulent serotype 2
      strains have not been fully identified. In this study a simple, rapid, and non
      destructive method was used to extract cell wall-associated proteins from SS2
      strains. Two virulent strains were compared with one avirulent strain by 2
      dimensional electrophoresis (2DE). When the results of the 2DE analyses were
      combined with the results of mass spectrometry analyses, a total of 40 unique
      proteins were identified, including 26 antigens (2DE immunoblotting was used as a
      preliminary study). In addition to a known virulence factor, muramidase-released
      protein, two new proteins, catabolite control protein A and leucyl
      aminopeptidase, and nine potential virulence factors were also identified. The
      formers may be a potential virulence regulator or drug target, and the latter
      contains plasminogen-binding proteins and molecular chaperones. Our results
      complemented previous immunoproteomics studies of SS2 strains.

PMID- 20824278
TI  - Differential effects of testosterone, dihydrotestosterone and estradiol on
      carotenoid deposition in an avian sexually selected signal.
AB  - Recent studies have demonstrated that carotenoid-based traits are under the
      control of testosterone (T) by up-regulation of carotenoid carriers
      (lipoproteins) and/or tissue-specific uptake of carotenoids. T can be converted
      to dihydrotestosterone (DHT) and estradiol (E2), and variation in conversion rate
      may partly explain some contradictory findings in the literature. Moreover, most
      studies on the effect of T on sexual signals have focused on the male sex only,
      while in many species females show the same signal, albeit to a lesser extent. We
      studied the effects of T, DHT, and E2 treatment in male and female diamond doves
      Geopelia cuneata in which both sexes have an enlarged red eye ring, which is more
      pronounced in males. We first showed that this periorbital ring contains very
      high concentration of carotenoids, of which most are lutein esters. Both T and
      DHT were effective in enhancing hue, UV-chroma and size in both sexes, while E2
      was ineffective. However, E2 dramatically increased the concentration of
      circulating lipoproteins. We conclude that in both sexes both color and size of
      the secondary sexual trait are androgen dependent. The action of androgens is
      independent of lipoproteins regulation. Potential mechanisms and their
      consequences for trade-off are discussed.

PMID- 20824279
TI  - Serum CCL23 levels are increased in patients with systemic sclerosis.
AB  - The aim of this study is to determine serum CCL23 levels and their clinical
      associations in patients with systemic sclerosis (SSc). Serum CCL23 levels were
      examined by ELISA in 66 patients with SSc, 20 patients with systemic lupus
      erythematosus, 20 patients with dermatomyositis, and 33 healthy individuals.
      Serum CCL23 levels were elevated in SSc patients (389.1 +/- 199.2 pg/mL) compared
      with healthy individuals (94.1 +/- 85.6 pg/mL; P < 0.001) and patients with
      systemic lupus erythematosus (43.4 +/- 39.3 pg/mL; P < 0.001) or dermatomyositis
      (132.1 +/- 104.5 pg/mL; P < 0.001). Among SSc patients, there were no differences
      in serum CCL23 levels between those with limited cutaneous SSc and those with
      diffuse cutaneous SSc. SSc patients with elevated CCL23 levels were found to have
      shorter disease duration than those with normal CCL23 levels (P < 0.001).
      Furthermore, raised CCL23 levels were associated with a higher frequency of
      pulmonary arterial hypertension (P < 0.05). The results show that serum CCL23
      level was increased in the early phase of SSc. CCL23 could be associated with
      induction of SSc and as such would be a serologically useful marker for disease
      activity.

PMID- 20824280
TI  - Changes in spring-mass model characteristics during repeated running sprints.
AB  - This study investigated fatigue-induced changes in spring-mass model
      characteristics during repeated running sprints. Sixteen active subjects
      performed 12 * 40 m sprints interspersed with 30 s of passive recovery. Vertical
      and anterior-posterior ground reaction forces were measured at 5-10 m and 30-35 m
      and used to determine spring-mass model characteristics. Contact (P < 0.001),
      flight (P < 0.05) and swing times (P < 0.001) together with braking, push-off and
      total stride durations (P < 0.001) lengthened across repetitions. Stride
      frequency (P < 0.001) and push-off forces (P < 0.05) decreased with fatigue,
      whereas stride length (P = 0.06), braking (P = 0.08) and peak vertical forces (P
      = 0.17) changes approached significance. Center of mass vertical displacement (P
      < 0.001) but not leg compression (P > 0.05) increased with time. As a result,
      vertical stiffness decreased (P < 0.001) from the first to the last repetition,
      whereas leg stiffness changes across sprint trials were not significant (P >
      0.05). Changes in vertical stiffness were correlated (r > 0.7; P < 0.001) with
      changes in stride frequency. When compared to 5-10 m, most of ground reaction
      force-related parameters were higher (P < 0.05) at 30-35 m, whereas contact time,
      stride frequency, vertical and leg stiffness were lower (P < 0.05). Vertical
      stiffness deteriorates when 40 m run-based sprints are repeated, which alters
      impact parameters. Maintaining faster stride frequencies through retaining higher
      vertical stiffness is a prerequisite to improve performance during repeated
      sprinting.

PMID- 20824281
TI  - Decreased variability in postural control strategies in young people with non
      specific low back pain is associated with altered proprioceptive reweighting.
AB  - Optimal postural control is an essential capacity in daily life and can be highly
      variable. The purpose of this study was to investigate if young people have the
      ability to choose the optimal postural control strategy according to the postural
      condition and to investigate if non-specific low back pain (NSLBP) influences the
      variability in proprioceptive postural control strategies. Young individuals with
      NSLBP (n = 106) and healthy controls (n = 50) were tested on a force plate in
      different postural conditions (i.e., sitting, stable support standing and
      unstable support standing). The role of proprioception in postural control was
      directly examined by means of muscle vibration on triceps surae and lumbar
      multifidus muscles. Root mean square and mean displacements of the center of
      pressure were recorded during the different trials. To appraise the
      proprioceptive postural control strategy, the relative proprioceptive weighting
      (RPW, ratio of ankle muscles proprioceptive inputs vs. back muscles
      proprioceptive inputs) was calculated. Postural robustness was significantly less
      in individuals with NSLBP during the more complex postural conditions (p < 0.05).
      Significantly higher RPW values were observed in the NSLBP group in all postural
      conditions (p < 0.05), suggesting less ability to rely on back muscle
      proprioceptive inputs for postural control. Therefore, healthy controls seem to
      have the ability to choose a more optimal postural control strategy according to
      the postural condition. In contrast, young people with NSLBP showed a reduced
      capacity to switch to a more multi-segmental postural control strategy during
      complex postural conditions, which leads to decreased postural robustness.

PMID- 20824282
TI  - The effects of pre-ejection period on post-exercise systolic blood pressure
      estimation using the pulse arrival time technique.
AB  - Pulse arrival time (PAT) is comprised of the vascular transit time (TT) through
      the arterial system and the pre-ejection period (PEP) in the heart. It has been
      used to predict arterial blood pressure (BP) without using a cuff. The aim of
      this study was to investigate the effects of including the PEP on the accuracy of
      cuffless systolic BP (SBP) estimation using the PAT technique in post-exercise
      recovery. Experiments were conducted on 22 normotensive participants. PAT, TT and
      PEP were determined from simultaneous measurements of the electrocardiogram,
      photoplethysmogram and impedance cardiogram. Moderate exercise induced
      significant (p < 0.05) increases in SBP and heart rate and significant (p < 0.05)
      decreases in PEP and PAT. Diastolic blood pressure and TT only varied
      insignificantly (p > 0.05). SBP was moderately correlated with PEP (r = -0.61)
      and PAT (r = -0.81). PAT and PEP were moderately correlated (r = 0.67). When SBP
      was estimated using least-squares methods, the differences between the measured
      and predicted SBP using PEP, PAT and TT were 0.0 +/- 6.6, 0.0 +/- 4.9 and 0.0 +/-
      9.3 mmHg, respectively. The findings suggested that PAT gives the best SBP
      prediction and PEP has some potential to predict blood pressure. The inclusion of
      PEP in the PAT measurement is necessary to facilitate accurate cuffless blood
      pressure prediction after exercise.

PMID- 20824283
TI  - Evaluation of muscle fatigue during 100-m front crawl.
AB  - The aim of this study was to evaluate muscle fatigue in upper body muscles during
      100-m all-out front crawl. Surface electromyogram (EMG) was collected from the
      pectoralis major, latissimus dorsi and triceps brachii muscles of 11 experienced
      swimmers. Blood lactate concentration level increased to 14.1 +/- 2.9 mmol l(-1)
      5 min after the swim. The velocity, stroke length and stroke rate calculated
      based on video analysis decreased by 15.0, 5.8 and 7.4%, respectively, during the
      swim. EMG amplitude of the triceps and the lower part of the latissimus muscles
      increased, whilst the mean power frequency (MNF) of all muscles significantly
      decreased by 20-25%. No significant differences in the relative MNF decrease were
      observed amongst the muscles; however, the differences in the rate of the MNF
      decrease between the lower part of the latissimus and the triceps brachii muscles
      were found (P < 0.05). The time of rest between the muscle activation of the two
      consecutive arm strokes at the end of swimming was extended (P < 0.05). It was
      concluded that 100-m all-out crawl induced significant fatigue with no evident
      differences amongst the analysed muscles.

PMID- 20824284
TI  - Lung defects in neonatal and adult stromal-derived factor-1 conditional knockout
      mice.
AB  - Stromal-derived factor (SDF)-1/CXCL12 is a cytokine that is involved in
      organogenesis, hematopoiesis, chemoattraction, and wound healing. An SDF-1
      knockout mouse (SDF-1(-/-)) has provided important insights into the role of SDF
      1 in fetal development. Because the SDF-1 knockout is lethal in the perinatal
      period, we have created a conditional SDF-1 knockout mouse. In the present study,
      we induced conditionally knocked out SDF-1 in neonatal mice and found that lung
      development was compromised; neonatal lungs showed increased alveolar airspace
      and abnormal ultrastructure. Conditional knockout of SDF-1 in adult mice resulted
      in an emphysemic morphology, with increased alveolar airspace and thickened
      alveolar septa. Fluorescence angiography showed pulmonary vessel hyperdilation.
      To determine whether the hyperdilation involved nitric oxide, we inhibited
      endothelial nitric oxide synthase (eNOS) with N (G)-nitro-L- arginine methyl
      ester. This resulted in the inhibition of pulmonary vessel hyperdilation. Western
      blot results showed increased phosphorylation of eNOS in our induced SDF-1
      knockout mice, indicating that eNOS is normally repressed in the presence of SDF
      1, and that activation of eNOS contributes to pulmonary pathology. Thus, a
      conditional knockout mouse has been successfully created for SDF-1; initial
      characterization indicates that SDF-1 is intimately involved in lung development
      and physiology.

PMID- 20824285
TI  - Monocyte and macrophage heterogeneity and Toll-like receptors in the lung.
AB  - Mononuclear phagocytes are crucial components of the innate host defense system.
      Cells such as macrophages and monocytes phagocytose and process pathogens,
      produce inflammatory mediators, and link the innate and the adaptive immune
      systems. The role of innate immune receptors such as Toll-like receptors (TLRs)
      in the recognition of pathogens is critical for mounting a precise and targeted
      immune response. This review focuses attention on the development of monocytes
      and macrophages, various populations of macrophages, and the expression and
      function of TLRs on macrophages.

PMID- 20824286
TI  - Modulation of B cell responses by Toll-like receptors.
AB  - B lymphocytes are well known because of their key role in mediating humoral
      immune responses. Upon encounter with antigen and on cognate interaction with T
      cells, they differentiate into antibody-secreting plasma cells, which are
      critical for protection against a variety of pathogens. In addition to their
      antibody-production function, B cells are efficient antigen-presenting cells and
      express a variety of pathogen recognition receptors (PRRs). Engagement of these
      PRRs with their respective ligands results in cytokine and chemokine secretion
      and the upregulation of co-stimulatory molecules. These events constitute innate
      immune responses. Toll-like receptor (TLR) activation provides a third signal for
      B cell activation and is essential for optimal antigen-specific antibody
      responses. In some situations, TLR activation in B cells can result in
      autoimmunity. The purpose of this review is to provide some insights into the way
      that TLRs influence innate and adaptive B cell responses.

PMID- 20824287
TI  - Mucosal dendritic cell diversity in the gastrointestinal tract.
AB  - The discovery of dendritic cells (DCs) in skin by Paul Langerhans in 1868
      identified a cell type which has since been recognized as a key link between
      innate and adaptive immunity. DCs originate from bone marrow and disseminate
      through blood to all tissues in the body, and distinct DC subpopulations have
      been identified in many different tissues. DC diversity is apparent throughout
      all mucosal surfaces of the body, but the focus of this review article is DC
      diversity throughout the gastro-intestinal tract (GIT). DC subpopulations have
      been well characterized in the oral cavity and small intestine, but DC
      characterization in other regions, such as the esophagus and stomach, is limited.
      Substantial research has focused on DC function during disease, but understanding
      the regulation of inflammation and the induction of acquired immune responses
      requires combined phenotypic and functional characterization of individual DC
      subpopulations. Furthermore, little is known regarding mucosal DC subpopulations
      in the GIT of the neonate and how these DC populations change following
      colonization by commensal microflora. The current review will highlight mucosal
      DC diversity and discuss factors that may influence mucosal DC differentiation.

PMID- 20824288
TI  - The association between oral microorgansims and aspiration pneumonia in the
      institutionalized elderly: review and recommendations.
AB  - Aspiration pneumonia is a leading cause of illness and death in persons who
      reside in long-term-care facilities and, combined with the lack of proper oral
      health care and services, the risk of aspiration pneumonia rises. The purpose of
      this article is to review recent literature on oral hygiene and oral care in long
      term-care facilities and report new findings regarding associated risks for
      aspiration pneumonia, as well as research on oral care and health outcomes. The
      PubMed MeSH database was utilized to direct a specific search by entering terms
      "aspiration pneumonia" and "oral hygiene" from 1970 to 2009, which yielded 34
      articles. The Ovid and Google Scholar databases were utilized as well and
      provided no additional references for the two terms. A manual search of
      references from other articles, including three systematic reviews published over
      the past decade, provided additional information regarding oral microorganisms
      and respiratory pathogens, as well as investigations of oral care. Finally, a
      brief but comprehensive introductory review was organized regarding oral
      microorganisms, biofilm, periodontal disease, and pneumonia to establish a
      framework for discussion. Overall, studies suggest (1) an association between
      poor oral hygiene and respiratory pathogens, (2) a decrease in the incidence of
      respiratory complications when patients are provided chemical or mechanical
      interventions for improved oral care, (3) the complex nature of periodontal
      disease and aspiration pneumonia make direct connections between the two
      challenging, and (4) additional studies are warranted to determine adequate oral
      hygiene protocols for nursing home patients to further reduce the incidence of
      aspiration pneumonia.

PMID- 20824289
TI  - DPEP1, expressed in the early stages of colon carcinogenesis, affects cancer cell
      invasiveness.
AB  - BACKGROUND: We investigated changes in the gene expression profile in colon
      cancer in order to identify gene markers that may be useful in the management of
      this disease. METHODS: The Cancer Genome Anatomy Project was used to detect
      differences in gene expression between normal and cancer tissue. The
      overexpression of dipeptidase-1 (DPEP1) in cancer tissue was confirmed in a
      sample of 76 patients by real-time PCR. To identify the function of DPEP1, RNA
      interference (RNAi) was used to inactivate this gene in the colon cancer cell
      line. Immunohistochemical analysis was performed to characterize the pattern of
      DPEP1 expression in colon cancer. RESULTS: DPEP1 expression in cancer was
      significantly higher than that in normal tissue. However, DPEP1 expression
      decreased with pathological differentiation, lymph-node and distant metastasis.
      Patients with tumors with decreased DPEP1 expression showed a poorer prognosis,
      and this was also true of patients with tumors who are treated with curative
      intent. RNAi-mediated DPEP1 reduction in the colon cancer cell line did not
      result in cell proliferation or apoptosis, but was associated with an increased
      invasive ability. DPEP1 protein was observed on the apical side of the cancer
      cells, and is expressed in the early stages of carcinogenesis, even in adenomas
      of both sporadic colorectal cancer and familial adenomatous polyposis patients.
      CONCLUSIONS: DPEP1 expression in normal colonic mucosa is very low, but it is
      highly expressed in colorectal adenoma and cancer specimens and is negatively
      correlated with parameters of pathological aggressiveness and poor prognosis.
      DPEP1 is expressed in the early stages of colon carcinogenesis and affects cancer
      cell invasiveness.

PMID- 20824290
TI  - Serum IgG4-negative autoimmune pancreatitis.
AB  - BACKGROUND: Autoimmune pancreatitis (AIP) is considered to be a pancreatic lesion
      of IgG4-related systemic disease, but about 20% of AIP patients do not have
      elevated serum IgG4 levels. This study aimed to clarify the pathophysiology of
      AIP patients without elevated serum IgG4 levels. METHODS: Fifty-eight AIP
      patients were divided into 2 groups: those with elevated serum IgG4 levels (>135
      mg/dl; SIgG4-positive AIP) and those without (SIgG4-negative AIP). The 2 groups'
      clinical, serological, radiological, and histological findings, as well as
      salivary and lacrimal gland function, were compared. RESULTS: Serum IgG4 levels
      were elevated in 45 AIP patients and normal in 13 patients. In SIgG4-negative AIP
      patients, the female ratio tended to be high; obstructive jaundice was less
      likely; abdominal pain and acute pancreatitis were more likely; segmental
      swelling of the pancreatic body and/or tail was more common; sclerosing
      extrapancreatic lesions, salivary and lacrimal gland dysfunction, and abundant
      infiltration of IgG4-positive plasma cells in the gastric mucosa were less
      likely; and conservative follow-up was sometimes implemented. Histological
      examination of the pancreas of SIgG4-negative AIP showed lymphoplasmacytic
      sclerosing pancreatitis (LPSP) rather confined to the pancreas (n = 4),
      inadequate material (n = 2), and pancreatic fibrosis showing infiltration of
      lymphocytes without infiltration of IgG4-positive cells or neutrophils (n = 2).
      CONCLUSIONS: Clinicopathological features of SIgG4-negative AIP differed from
      those of SIgG4-positive AIP. Some SIgG4-negative AIP cases are LPSP rather
      confined to the pancreas. SIgG4-negative AIP may include idiopathic duct-centric
      pancreatitis (IDCP) or sclerosing pancreatitis other than LPSP or IDCP, but
      further studies are needed to clarify this issue.

PMID- 20824291
TI  - Mechanisms by which thiazolidinediones induce anti-cancer effects in cancers in
      digestive organs.
AB  - Increasing evidence suggests that thiazolidinediones (TZDs) could have a
      therapeutic potential for patients with cancers. Here, the evidence on the
      mechanisms by which TZDs could contribute to different steps of cancer biology in
      the digestive system is summarized. According to studies, TZDs induce anti-cancer
      actions through 3 main pathways: (1) cell growth arrest, (2) induction of
      apoptosis, and (3) inhibition of cell invasion. Cell growth arrest is induced by
      an increased level of p27(Kip1). p27(Kip1) accumulation results from the
      inhibition of the ubiquitin-proteasome system and/or inhibition of MEK-ERK
      signaling. TZDs induce apoptosis through increased levels of apoptotic molecules,
      such as p53 and PTEN and/or decreased level of anti-apoptotic molecules, such as
      Bcl-2 and survivin. Inhibition of MEK-ERK signaling-mediated up-regulation of E
      cadherin and claudin-4, and/or decreased expression of matrix metalloproteinases
      (MMPs) such as MMP-2 and MMP-9, play a role in the TZD-induced inhibition of
      cancer cell invasion. Thus, TZDs are capable of inducing anti-tumor action in a
      variety of ways in gastrointestinal cancers.

PMID- 20824292
TI  - A rare case of extradural neurenteric cyst with supratentorial and infratentorial
      extension.

PMID- 20824293
TI  - Elevated O-GlcNAc-dependent signaling through inducible mOGT expression
      selectively triggers apoptosis.
AB  - O-linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAc addition to
      numerous cellular proteins including transcription and nuclear pore complexes and
      plays a key role in cellular signaling. One differentially spliced isoform of OGT
      is normally targeted to mitochondria (mOGT) but is quite cytotoxic when expressed
      in cells compared with the ncOGT isoform. To understand the basis of this
      selective cytotoxicity, we constructed a fully functional ecdysone-inducible GFP
      OGT. Elevated GFP-OGT expression induced a dramatic increase in intracellular O
      GlcNAcylated proteins. Furthermore, enhanced OGT expression efficiently triggered
      programmed cell death. Apoptosis was dependent upon the unique N-terminus of
      mOGT, and its catalytic activity. Induction of mOGT expression triggered
      programmed cell death in every cell type tested including INS-1, an insulin
      secreting cell line. These studies suggest that deregulated activity of the
      mitochondrially targeted mOGT may play a role in triggering the programmed cell
      death observed with diseases such as diabetes mellitus and neurodegeneration.

PMID- 20824294
TI  - Halorussus rarus gen. nov., sp. nov., a new member of the family Halobacteriaceae
      isolated from a marine solar saltern.
AB  - Two halophilic archaeal strains TBN4(T) and TBN5 were isolated from Taibei marine
      solar saltern in Jiangsu, China. Both strains showed light red-pigmented colonies
      and their cells were rod, motile and Gram-stain-negative. They were able to grow
      at 25-50 degrees C (optimum 37 degrees C), at 1.4-4.3 M NaCl (optimum 2.1 M
      NaCl), at 0-1.0 M MgCl(2) (optimum 0.005 M MgCl(2)) and at pH 6.0-9.0 (optimum pH
      7.0). Their cells lyse in distilled water and minimal NaCl concentration to
      prevent cell lysis is 8% (w/v). The major polar lipids of the two strains were PG
      (phosphatidylglycerol), PGP-Me (phosphatidylglycerol phosphate methyl ester), PGS
      (phosphatidylglycerol sulfate) and five glycolipids chromatographically identical
      to S-TGD-1 (sulfated galactosyl mannosyl glucosyl diether), S-DGD-1 (sulfated
      mannosyl glucosyl diether), TGD-1 (galactosyl mannosyl glucosyl diether), DGD-1
      (mannosyl glucosyl diether) and DGD-2 (an unknown diglycosyl diether).
      Phylogenetic analysis revealed that TBN4(T) and strain TBN5 formed a distinct
      clade with genus Haladaptatus (showing 90.0-90.9% 16S rRNA gene similarities).
      The DNA G + C content of strain TBN4(T) and strain TBN5 are 66.1 and 65.4 mol%,
      respectively. The DNA-DNA hybridization value between strain TBN4(T) and strain
      TBN5 was 94.3%. The phenotypic, chemotaxonomic and phylogenetic properties
      suggest that strain TBN4(T) and strain TBN5 represent a novel species in a new
      genus within the family Halobacteriaceae, for which the name Halorussus rarus
      gen. nov., sp. nov. is proposed. The type strain is TBN4(T) (=CGMCC 1.10122(T) =
      JCM 16429(T)).

PMID- 20824295
TI  - Imaging of acquired cystic disease-associated renal cell carcinoma by contrast
      enhanced ultrasonography with perflubutane microbubbles and positron emission
      tomography-computed tomography.
AB  - The preoperative assessment of renal cell carcinoma (RCC) complicated with
      acquired renal cystic disease in a 63-year-old male patient on long-term
      hemodialysis (30 years and 8 months) that was difficult because of no or poor
      contrast enhancement by dynamic CT scan is reported. Contrast-enhanced
      ultrasonography with perflubutane microbubbles and positron emission tomography
      computed tomography (PET-CT) with 18F-fluorodeoxy glucose (FDG) in addition to
      dynamic CT were effective and useful for preoperative assessment of this patient.
      The pathological subtype of RCC in this patient was acquired cystic disease
      associated RCC (ACD-associated RCC), which has been newly defined by Tickoo et
      al. (Am J Surg Pathol 30:141-153, 2006).

PMID- 20824296
TI  - Elevated serum levels of interleukin-18 in patients with overt diabetic
      nephropathy: effects of miglitol.
AB  - BACKGROUND: Interleukin-18 (IL-18), a pro-inflammatory cytokine, is a predictor
      of cardiovascular and renal disease in diabetic patients. Postprandial
      hyperglycemia is one of the important factors contributing to an increase in the
      circulating pro-inflammatory cytokine levels. This study investigated the effect
      of miglitol, an alpha-glucosidase inhibitor, on postprandial hyperglycemia and IL
      18 levels in diabetic patients with nephropathy. METHODS: Fifteen Japanese
      diabetic patients with persistent proteinuria and preserved renal function were
      recruited. The patients received 50 mg miglitol thrice daily after the baseline
      examinations and were followed up for 12 weeks. A meal tolerance test was
      performed on eight patients at baseline and week 12. The fasting miglitol
      concentration was measured in seven patients just before the meal tolerance test.
      RESULTS: There were no changes in the body weight, blood pressure, liver and
      renal function, and proteinuria from baseline to week 12. However, the levels of
      glycated hemoglobin and interleukin 18 significantly decreased from baseline to
      week 12. During the meal tolerance test, plasma glucose was significantly
      decreased 60 min after treatment with miglitol, whereas the serum concentration
      of insulin was not changed. Fasting and postprandial levels of IL-18 were
      significantly decreased from baseline to week 12. Serum miglitol concentrations
      showed a significantly negative correlation with eGFR (r = -0.82, p = 0.02).
      However, the serum miglitol concentrations did not changed during the course of
      this study. CONCLUSION: Miglitol improved postprandial hyperglycemia and reduced
      serum IL-18 levels in patients with stage 3 diabetic nephropathy. Miglitol may
      therefore prevent atherosclerotic diseases and diabetic micro-vascular
      complications through decreasing glucose swings and/or the circulating IL-18
      level.

PMID- 20824297
TI  - Anti-ribosomal P protein antibody induces Th1 responses by enhancing the
      production of IL-12 in activated monocytes.
AB  - Autoantibodies to ribosomal P proteins (anti-P) are detected in 12-16% of
      patients with systemic lupus erythematosus (SLE), and have been found to be
      associated with some manifestations, including lupus psychosis, nephritis and
      hepatitis. We have recently disclosed that anti-P react with activated human
      peripheral blood monocytes, and enhance their production of tumor necrosis factor
      alpha and interleukin (IL)-6. It is also possible that anti-P might regulate
      other monocyte functions, including the regulation of T helper (Th) responses.
      The current study was therefore undertaken to explore the effects of anti-P on
      the induction of Th1 responses. Peripheral blood mononuclear cells (PBMC) from
      healthy donors were cultured with affinity-purified anti-P or control IgG. Highly
      purified monocytes were cultured with interferon (IFN)-gamma in the presence of
      anti-P or normal IgG. Anti-P significantly enhanced the production of IFN-gamma
      by PBMC. Of note, anti-IL-12 monoclonal antibodies almost completely abrogated
      the anti-P-mediated upregulation of the IFN-gamma production of PBMC.
      Accordingly, anti-P significantly enhanced the production of IL-12 by activated
      monocytes. These results indicate that anti-P induce Th1 responses by
      upregulating the production of IL-12 by activated monocytes. The data therefore
      suggest that anti-P play an important role in the pathogenesis of SLE through the
      promotion of Th1 responses.

PMID- 20824298
TI  - A case of disseminated DLE complicated by atopic dermatitis and Sjogren's
      syndrome: link between hypohidrosis and skin manifestations.
AB  - We report an unusual case of disseminated discoid lupus erythematosus (DLE)
      complicated by pre-existing atopic dermatitis (AD) and late-onset Sjogren's
      syndrome (SS). Disseminated DLE lesions were sparse on the expected sites for AD,
      such as the medial region of the extremities or v-neck area. The patient
      fulfilled the diagnostic criteria for AD and SS but not for systemic lupus
      erythematosus. Histopathological analysis of the crusted erythematous lesions
      revealed typical DLE with few FoxP3(+) cells and a moderate number of IL-17(+)
      cells. A quantitative sweating test showed impaired sweating of both lesional and
      non-lesional skin due to underlying hypohidrosis that was related to AD and SS.
      This finding suggests that dissemination of DLE was triggered by scratching and a
      Kobner phenomenon-like effect related to hypohidrotic and xerotic skin. To the
      best of our knowledge, this is the first reported case of disseminated DLE
      complicated by AD and SS.

PMID- 20824299
TI  - Analysis of C-reactive protein levels and febrile tendency after joint surgery in
      rheumatoid arthritis patients treated with a perioperative 4-week interruption of
      tocilizumab.

PMID- 20824300
TI  - A mobile tele-radiology imaging system with JPEG2000 for an emergency care.
AB  - The aim of this study was to design a tele-radiology imaging system for rapid
      emergency care via mobile networks and to assess the diagnostic feasibility of
      the Joint Photographic Experts Group 2000 (JPEG2000) radiological imaging using
      portable devices. Rapid patient information and image exchange is helpful to make
      clinical decisions. We assessed the usefulness of the mobile tele-radiology
      system by measuring both a quantitative method, PNSR calculation, for image
      qualities, and its transmission time via mobile networks in different mobile
      networks, respectively; code division multiple access evolution-data optimized,
      wireless broadband, and high-speed downlink packet access; and the feasibility of
      the JPEG2000 computed tomography (CT) images by qualitatively assessing with the
      Alberta stroke program early CT score method with 12 CT image cases (seven normal
      and five abnormal cases). We found that the quality of the JPEG2000 radiological
      images was satisfied quantitatively and was judged as acceptable qualitatively at
      5:1 and 10:1 compression levels for the mobile tele-radiology imaging system. The
      JPEG2000-format radiological images achieved a fast transmission while
      maintaining a diagnosis quality on a portable device via mobile networks.
      Unfortunately, a PDA device, having a limited screen resolution, posed
      difficulties in reviewing the JPEG2000 images regardless of the compression
      levels. An ultra mobile PC was preferable to study the medical image. The mobile
      tele-radiology imaging systems supporting JPEG2000 image transmission can be
      applied to actual emergency care services under mobile computing environments.

PMID- 20824301
TI  - Is it possible to predict heart rate and range during enhanced cardiac CT scan
      from previous non-enhanced cardiac CT?
AB  - The effect of heart rate and variation during cardiac computed tomography (CT) on
      the examination quality. The purpose of this study is to investigate whether it
      is possible to predict heart rate and range during enhanced cardiac computed CT
      scan from previous non-enhanced cardiac CT scan. Electrocardiograph (ECG) files
      from 112 patients on three types of cardiac 64-slice CT (non-enhanced,
      prospective ECG-triggered and retrospective ECG-gated enhanced scans) were
      recorded. The mean heart rate, range (defined as difference between maximal and
      minimal heart rates) and the range ratio (defined as maximal heart rate divided
      by minimal heart rate) during the scans were compared. Scan time was 4.8, 4.6,
      and 7.3 s on non-enhanced, prospective ECG-triggered and retrospective ECG-gated
      scans, respectively (p < 0.0001). The heart rates were not significantly
      different (60 +/- 9 beats per minute (bpm), 60 +/- 9 and 61 +/- 10 bpm; p =
      0.64). Heart rate on the enhanced scan markedly correlated with that of the non
      enhanced scan (r = 0.78 and 0.74). In contrast, the ranges of heart rate were 2
      +/- 5, 4 +/- 8, and 8 +/- 21 bpm, with different range ratios (1.04, 1.07, and
      1.14; p < 0.0001). Correlation of heart rate ranges between non-enhanced scan
      versus prospective ECG-triggered scan was low (r = 0.27) and that between non
      enhanced scan versus retrospective ECG-gated scan negligible (r = -0.027).Heart
      rate on enhanced cardiac CT, in most cases, can be predicted from a non-enhanced
      scan. Heart rate range on enhanced cardiac CT, however, is hard to predict from
      the non-enhanced scan.

PMID- 20824302
TI  - Empirical investigation of radiologists' priorities for PACS selection: an
      analytical hierarchy process approach.
AB  - Picture archiving and communication systems (PACS) are being widely adopted in
      radiology practice. The objective of this study was to find radiologists'
      perspective on the relative importance of the required features when selecting or
      developing a PACS. Important features for PACS were identified based on the
      literature and consultation/interviews with radiologists. These features were
      categorized and organized into a logical hierarchy consisting of the main
      dimensions and sub-dimensions. An online survey was conducted to obtain data from
      58 radiologists about their relative preferences. Analytical hierarchy process
      methodology was used to determine the relative priority weights for different
      dimensions along with the consistency of responses. System continuity and
      functionality was found to be the most important dimension, followed by system
      performance and architecture, user interface for workflow management, user
      interface for image manipulation, and display quality. Among the sub-dimensions,
      the top two features were: security, backup, and downtime prevention; and voice
      recognition, transcription, and reporting. Structured reporting was also given
      very high priority. The results point to the dimensions that can be critical
      discriminators between different PACS and highlight the importance of faster
      integration of the emerging developments in radiology into PACS.

PMID- 20824303
TI  - An automated DICOM database capable of arbitrary data mining (including radiation
      dose indicators) for quality monitoring.
AB  - The U.S. National Press has brought to full public discussion concerns regarding
      the use of medical radiation, specifically x-ray computed tomography (CT), in
      diagnosis. A need exists for developing methods whereby assurance is given that
      all diagnostic medical radiation use is properly prescribed, and all patients'
      radiation exposure is monitored. The "DICOM Index Tracker(c)" (DIT) transparently
      captures desired digital imaging and communications in medicine (DICOM) tags from
      CT, nuclear imaging equipment, and other DICOM devices across an enterprise. Its
      initial use is recording, monitoring, and providing automatic alerts to medical
      professionals of excursions beyond internally determined trigger action levels of
      radiation. A flexible knowledge base, aware of equipment in use, enables
      automatic alerts to system administrators of newly identified equipment models or
      software versions so that DIT can be adapted to the new equipment or software. A
      dosimetry module accepts mammography breast organ dose, skin air kerma values
      from XA modalities, exposure indices from computed radiography, etc. upon
      receipt. The American Association of Physicists in Medicine recommended a
      methodology for effective dose calculations which are performed with CT units
      having DICOM structured dose reports. Web interface reporting is provided for
      accessing the database in real-time. DIT is DICOM-compliant and, thus, is
      standardized for international comparisons. Automatic alerts currently in use
      include: email, cell phone text message, and internal pager text messaging. This
      system extends the utility of DICOM for standardizing the capturing and computing
      of radiation dose as well as other quality measures.

PMID- 20824304
TI  - A fast and fully automatic method for cerebrovascular segmentation on time-of
      flight (TOF) MRA image.
AB  - The precise three-dimensional (3-D) segmentation of cerebral vessels from
      magnetic resonance angiography (MRA) images is essential for the detection of
      cerebrovascular diseases (e.g., occlusion, aneurysm). The complex 3-D structure
      of cerebral vessels and the low contrast of thin vessels in MRA images make
      precise segmentation difficult. We present a fast, fully automatic segmentation
      algorithm based on statistical model analysis and improved curve evolution for
      extracting the 3-D cerebral vessels from a time-of-flight (TOF) MRA dataset.
      Cerebral vessels and other tissue (brain tissue, CSF, and bone) in TOF MRA
      dataset are modeled by Gaussian distribution and combination of Rayleigh with
      several Gaussian distributions separately. The region distribution combined with
      gradient information is used in edge-strength of curve evolution as one novel
      mode. This edge-strength function is able to determine the boundary of thin
      vessels with low contrast around brain tissue accurately and robustly. Moreover,
      a fast level set method is developed to implement the curve evolution to assure
      high efficiency of the cerebrovascular segmentation. Quantitative comparisons
      with 10 sets of manual segmentation results showed that the average volume
      sensitivity, the average branch sensitivity, and average mean absolute distance
      error are 93.6%, 95.98%, and 0.333 mm, respectively. By applying the algorithm to
      200 clinical datasets from three hospitals, it is demonstrated that the proposed
      algorithm can provide good quality segmentation capable of extracting a vessel
      with a one-voxel diameter in less than 2 min. Its accuracy and speed make this
      novel algorithm more suitable for a clinical computer-aided diagnosis system.

PMID- 20824305
TI  - Novel chemo-sensitizing agent, ERW1227B, impairs cellular motility and enhances
      cell death in glioblastomas.
AB  - Glioblastomas display variable phenotypes that include increased drug-resistance
      associated with enhanced migratory and anti-apoptotic characteristics. These
      shared characteristics contribute to failure of clinical treatment regimens.
      Identification of novel compounds that promote cell death and impair cellular
      motility is a logical strategy to develop more effective clinical protocols. We
      recently described the ability of the small molecule, KCC009, a tissue
      transglutaminase (TG2) inhibitor, to sensitize glioblastoma cells to
      chemotherapy. In the current study, we synthesized a series of related compounds
      that show variable ability to promote cell death and impair motility in
      glioblastomas, irrespective of their ability to inhibit TG2. Each compound has a
      3-bromo-4,5-dihydroisoxazole component that presumably reacts with nucleophilic
      cysteine thiol residues in the active sites of proteins that have an affinity to
      the small molecule. Our studies focused on the effects of the compound, ERW1227B.
      Treatment of glioblastoma cells with ERW1227B was associated with both down
      regulation of the PI-3 kinase/Akt pathway, which enhanced cell death; as well as
      disruption of focal adhesive complexes and intracellular actin fibers, which
      impaired cellular mobility. Bioassays as well as time-lapse photography of
      glioblastoma cells treated with ERW1227B showed cell death and rapid loss of
      cellular motility. Mice studies with in vivo glioblastoma models demonstrated the
      ability of ERW1227B to sensitize tumor cells to cell death after treatment with
      either chemotherapy or radiation. The above findings identify ERW1227B as a
      potential novel therapeutic agent in the treatment of glioblastomas.

PMID- 20824306
TI  - Nano-crystalline hydroxyapatite bio-mineral for the treatment of strontium from
      aqueous solutions.
AB  - Hydroxyapatites were analysed using electron microscopy, X-ray diffraction (XRD)
      and X-ray fluorescence (XRF) analysis. Examination of a bacterially produced
      hydroxyapatite (Bio-HA) by scanning electron microscopy showed agglomerated nano
      sized particles; XRD analysis confirmed that the Bio-HA was hydroxyapatite, with
      an organic matter content of 7.6%; XRF analysis gave a Ca/P ratio of 1.55, also
      indicative of HA. The size of the Bio-HA crystals was calculated as ~25 nm from
      XRD data using the Scherrer equation, whereas Comm-HA powder size was measured as
      <= 50 MUm. The nano-crystalline Bio-HA was ~7 times more efficient in removing
      Sr(2+) from synthetic groundwater than Comm-HA. Dissolution of HA as indicated by
      the release of phosphate into the solution phase was higher in the Comm-HA than
      the Bio-HA, indicating a more stable biomaterial which has a potential for the
      remediation of contaminated sites.

PMID- 20824307
TI  - Post-colonization temporal genetic variation of an introduced fly, Rhagoletis
      completa.
AB  - Evolutionary biologists have been puzzled by the success of introduced species:
      despite founder effects that reduce genetic variability, invasive species are
      still successful at colonizing new environments. It is possible that the
      evolutionary processes during the post-colonization period may increase the
      genetic diversity and gene flow among invasive populations over time,
      facilitating their long-term success. Therefore, genetic diversity and population
      structure would be expected to show greater temporal variation for successful
      introduced populations than for native populations. We studied the population
      genetics of the walnut husk fly, Rhagoletis completa, which was introduced into
      California from the Midwestern US in the early 1900s. We used microsatellites and
      allozymes to genotype current and historic fly populations, providing a rare
      perspective on temporal variability in population genetic parameters. We found
      that introduced populations showed greater temporal fluctuations in allele
      frequencies than native populations. Some introduced populations also showed an
      increase in genetic diversity over time, indicating multiple introductions had
      occurred. Population genetic structure decreased in both native and introduced
      populations over time. Our study demonstrates that introduced species are not at
      equilibrium and post-colonization processes may be important in ameliorating the
      loss of genetic diversity associated with biological invasions.

PMID- 20824308
TI  - Multifunctional peptide-PEG intercalating conjugates: programmatic of gene
      delivery to the blood-brain barrier.
AB  - PURPOSE: To enhance transfection efficacy of pDNA through the application of
      multifunctional peptide-PEG-tris-acridine conjugates (pPAC) and the formation of
      biodegradable core-shell polyplexes for gene delivery to the blood-brain barrier
      (BBB). METHODS: pPAC-mediated transfection was compositionally optimized in mouse
      BBB cells (bEnd.3). Cellular uptake and trafficking, and brain accumulation of
      pDNA was evaluated by fluorescent imaging and histochemistry. We constructed anti
      MRP4 siRNA-producing vectors and evaluated the efficacy of MRP4 down-regulation
      of MRP4 by Western blot and qPCR, and its effect on the uptake of (3)H-AZT, an
      MRP4 substrate. RESULTS: A core-shell gene delivery system (GDS) was assembled
      from pDNA and pPAC, carrying multifunctional peptides with NLS, TAT, and brain
      specific BH, or ApoE sequences, and biodegradable pLPEI polyamine. This GDS
      demonstrated better cellular and nuclear accumulation, and a 25-fold higher
      transfection efficacy in slow-dividing bEnd.3 cells compared to ExGen500.
      Inclusion of brain-targeting pPAC enhanced in vivo accumulation of functional
      pDNA in brain capillaries. Treatment by encapsulated anti-MRP4 siRNA-producing
      pDNA caused transient down-regulation of MRP4, and, after intravenous injection
      in Balb/c mice, enhanced AZT uptake in the brain by 230-270%. CONCLUSIONS: The
      pPAC represent novel efficient components of GDS that could find various gene
      therapy applications, including genetic modulation of the BBB.

PMID- 20824309
TI  - Pulmonary gene silencing in transgenic EGFP mice using aerosolised chitosan/siRNA
      nanoparticles.
AB  - PURPOSE: This work describes the production and application of an aerosolised
      formulation of chitosan nanoparticles for improved pulmonary siRNA delivery and
      gene silencing in mice. METHODS: Aerosolised chitosan/siRNA nanoparticles were
      pneumatically formed using a nebulising catheter and sized by laser diffraction.
      In vitro silencing of aerosolised and non-aerosolised formulations was evaluated
      in an EGFP endogenous-expressing H1299 cell line by flow cytometry. Non-invasive
      intratracheal insertion of the catheter was used to study nanoparticle deposition
      by histological detection of Cy3-labeled siRNA and gene silencing in transgenic
      EGFP mouse lungs using a flow cytometric method. RESULTS: Flow cytometric
      analysis demonstrated minimal alteration in gene silencing efficiency before
      (68%) and after (62%) aerosolisation in EGFP-expressing H1299 cells.
      Intratracheal catheter administration in mice resulted in nanoparticle deposition
      throughout the entire lung in both alveoli and bronchiolar regions using low
      amounts of siRNA. Transgenic EGFP mice dosed with the aerosolised nanoparticle
      formulation showed significant EGFP gene silencing (68% reduction compared to
      mismatch group). CONCLUSIONS: This work provides a technology platform for
      effective pulmonary delivery and gene silencing of RNAi therapeutics with
      potential use in preclinical studies of respiratory disease treatment.

PMID- 20824310
TI  - Influence of crystallizing and non-crystallizing cosolutes on trehalose
      crystallization during freeze-drying.
AB  - PURPOSE: To study the influence of crystallizing and non-crystallizing cosolutes
      on the crystallization behavior of trehalose in frozen solutions and to monitor
      the phase behavior of trehalose dihydrate and mannitol hemihydrate during drying.
      METHODS: Trehalose (a lyoprotectant) and mannitol (a bulking agent) are widely
      used as excipients in freeze-dried formulations. Using differential scanning
      calorimetry (DSC) and X-ray diffractometry (XRD), the crystallization behavior of
      trehalose in the presence of (i) a crystallizing (mannitol), (ii) a non
      crystallizing (sucrose) solute and (iii) a combination of mannitol and a model
      protein (lactose dehydrogenase, catalase, or lysozyme) was evaluated. By
      performing the entire freeze-drying cycle in the sample chamber of the XRD, the
      phase behavior of trehalose and mannitol were simultaneously monitored. RESULTS:
      When an aqueous solution containing trehalose (4% w/v) and mannitol (2% w/v) was
      cooled to -40 degrees C at 0.5 degrees C/min, hexagonal ice was the only
      crystalline phase. However, upon warming the sample to the annealing temperature
      (-18 degrees C), crystallization of mannitol hemihydrate was readily evident.
      After 3 h of annealing, the characteristic XRD peaks of trehalose dihydrate were
      also observed. The DSC heating curve of frozen and annealed solution showed two
      overlapping endotherms, attributed by XRD to the sequential melting of trehalose
      dihydrate-ice and mannitol hemihydrate-ice eutectics, followed by ice melting.
      While mannitol facilitated trehalose dihydrate crystallization, sucrose
      completely inhibited it. In the presence of protein (2 mg/ml), trehalose
      crystallization required a longer annealing time. When the freeze-drying was
      performed in the sample chamber of the diffractometer, drying induced the
      dehydration of trehalose dihydrate to amorphous anhydrate. However, the final
      lyophiles prepared in the laboratory lyophilizer contained trehalose dihydrate
      and mannitol hemihydrate. CONCLUSIONS: Using XRD and DSC, the sequential
      crystallization of ice, mannitol hemihydrate, and trehalose dihydrate was
      observed in frozen solutions. Mannitol, by readily crystallizing as a
      hemihydrate, accelerated trehalose dihydrate crystallization in frozen solutions.
      However, by remaining amorphous, sucrose completely inhibited trehalose dihydrate
      crystallization. Crystallization of the lyoprotectantt in the model protein
      formulations might have serious implications on protein stability.

PMID- 20824311
TI  - Expressing and characterization of mLIN-41 in mouse early embryos and adult
      muscle tissues.
AB  - Heterochronical gene lin-41 plays an important role in regulate the timing of
      many decelopmental events in Caenorhabditis elegans. Mammalian developmental
      timing is poorly understood even though many tissues are under temporal control
      during development. The lin-41 homologues in mouse and chick has been isolated
      and its expression in developing limb buds and branchial arches has been reported
      by in situ (Kanamoto et al. in Dev Dyn 235:1142-1149, 2006; Lancman et al. in Dev
      Dyn 234:948-960, 2005; Schulman et al. in Dev Dyn 234:1046-1054, 2005), but the
      protein expression pattern in mouse adult tissue and embryo remained to be
      clarified. To help elucidate the expression of C. elegans lin-41 orthorlogs in
      mouse adult tissue and developmental embryo, lin-41 cDNA fragment was amplified
      from the mouse embryonic day 9.5(E9.5) mRNA and expressed in E. coli. The
      transcripts of mlin-41 and the protein level in mouse adult tissues and embryos
      from 9.5 to 13 days were detected by RT-PCR and western blot. RT-PCR and western
      blot showed the expression of mLIN-41 was detected in the mouse adult heart,
      muscle, and small intestine as well as in the day E9.5 to E12 embryos. Immuno
      localization of mLIN-41 in the day E10.5 embryo revealed that mLIN-41 was present
      in the neuro-epithelium and epithelial tissue covering the first and second
      branchial arch, somites and mesoderm cells, limb buds as well as the gut
      epithelium. The expression of mLIN-41 represented the tissue-specific expression
      pattern. Immuno-precipitation combine with MALDI-TOF mass spectrometry was used
      to identify the potential proteins interacting with LIN-41. Five potential
      specific proteins were obtained for future identification in mouse.

PMID- 20824312
TI  - Chlamydia screening of adolescent females: a survey of providers in Hawaii.
AB  - Hawaii currently ranks first among states for chlamydia screening of young women
      based on recent Healthcare Effectiveness Data and Information Set (HEDIS)
      measures and has consistently ranked in the top ten states in the US for annual
      reported chlamydia rates since 2002. A statewide provider survey was conducted in
      October 2007 and March 2008 to assess chlamydia screening practices and beliefs
      and identify potential barriers to screening. The overall reported screening rate
      for 15-19 year old females was 66.9% with significant differences by practice
      specialty (obstetrician/gynecologists were more likely to screen than family
      practitioners or pediatricians) and practice setting (higher rates of screening
      in non-private practice settings). Providers who were unaware of health plan
      reimbursement for screening and those who targeted screening only for clients
      perceived to be at "high risk" were significantly less likely to routinely
      provide screening. The Hawaii State Department of Health is currently working in
      consort with health care providers and the state's dominant health insurance
      carriers to address these issues through targeted provider educational
      interventions.

PMID- 20824313
TI  - Gender verification: a term whose time has come and gone.
AB  - The process of testing to determine gender in putatively female athletes was
      developed in order to prevent cheating, but has devolved instead into a clumsy
      mechanism for detecting disorders of sexual development (DSD's). In over thirty
      years of compulsory testing, individuals with DSD's have been stigmatized and
      some have been denied the right to compete, although frequently their condition
      provided no competitive advantage. More recent guidelines require testing only on
      a case-by-case basis; the South African runner Caster Semenya was the first major
      test of this policy, and her experience points to the need for a more sensitive
      and confidential process. In addition, her case dramatizes the inadequacy of the
      term "gender verification." Gender identity is a complex entity and resists
      simple classification. Sports authorities may set guidelines for who can compete,
      but they should refrain from taking on themselves the authority to decide who is
      and who is not a female.

PMID- 20824314
TI  - Fairer sex: the ethics of determining gender for athletic eligibility: commentary
      on "Beyond the Caster Semenya controversy: the case of the use of genetics for
      gender testing in sport".

PMID- 20824315
TI  - Beyond the Caster Semenya controversy: the case of the use of genetics for gender
      testing in sport.
AB  - Caster Semenya won the eight-hundred-meter title in the Berlin World Athletics
      Championships in 2009. Few hours after, Caster was at the center of a harsh
      contestation on gender. The International Association of Athletics Federations
      started an investigation, which was not respectful of her privacy. Caster's case
      highlights the need for an improvement in the awareness of genetic counseling
      principles amongst professionals, the public and various stakeholders. We
      critically examine the historical steps of gender verification in the Olympics,
      the violation of genetic counseling principles in Caster's case and outline some
      reflections on the complexity of the genetics of Disorders of sex development
      (DSD). Variability in both genotypes and phenotypes in DSD may not allow any
      etiological or functional classification at this point in time that could permit
      uncontroversial gender verification for fairer sport participation. We strongly
      suggest revisiting the pertinence of gender verification, and the process whereby
      this is done.

PMID- 20824316
TI  - A 15th century "Bambino" is the symbol of global maternal and child health.

PMID- 20824318
TI  - The impact of cyberbullying on substance use and mental health in a multiethnic
      sample.
AB  - The objective of this study was to examine the relationship between cyberbullying
      and mental health problems among a multiethnic sample of high school students in
      Hawai'i. A University-Community partnership was established to direct the
      research. Using a mixed-methods approach, we explored violence among Asian and
      Pacific Islander youth. In the first phase, focus groups were conducted to
      identify areas of youth concern and develop survey questions. Responses from 677
      high school students on interpersonal youth violence and risk and protective
      factors were utilized in this study. More than 1 in 2 youth (56.1%) had been
      victims of cyberbullying in the last year. Filipino and Samoan youth were more
      likely to report feeling badly about themselves as a result of cyberbullying.
      While cyberbullying and mental health problems varied by sex and ethnicity, we
      found that cyberbullying is widespread with serious potential consequences among
      Asian and Pacific Islander youth. A multifaceted approach is needed to reduce and
      prevent cyberbullying. School, family and community programs that strengthen
      positive relationships and promote safe use of technology provide promise for
      reducing cyberbullying.

PMID- 20824317
TI  - Risk factors for prenatal depressive symptoms among Hispanic women.
AB  - Prior studies of risk factors for depressive symptoms during pregnancy are sparse
      and the majority have focused on non-Hispanic white women. Hispanics are the
      largest minority group in the US and have the highest birth rates. We examined
      associations between pre and early pregnancy factors and depressive symptoms in
      early pregnancy among 921 participants in Proyecto Buena Salud, an ongoing cohort
      of pregnant Puerto Rican and Dominican women in Western Massachusetts. Depressive
      symptoms were assessed by the Edinburgh Postnatal Depression Scale (mean=13 weeks
      gestation) by bilingual interviewers who also collected data on sociodemographic,
      acculturation, behavioral, and psychosocial factors. A total of 30% of
      participants were classified as having depressive symptoms (EPDS scores>12) with
      mean+SD scores of 9.28+5.99. Higher levels of education (college/graduate school
      vs. <high school: RR=0.60, 95% CI 0.41-0.86), household income (Ptrend=0.02), and
      living with a spouse/partner (0.80; 95% CI 0.63-1.00) were independently
      associated with lower risk of depressive symptoms. There was the suggestion that
      failure to discontinue cigarette smoking with the onset of pregnancy (RR=1.32;
      95% CI 0.97-1.71) and English language preference (RR=1.33; 95% CI 0.96-1.70)
      were associated with higher risk. Single marital status, second generation in the
      U.S., and higher levels of alcohol consumption were associated with higher risk
      of depressive symptoms in univariate analyses, but were attenuated after
      adjustment for other risk factors. Findings in the largest, fastest-growing
      ethnic minority group can inform intervention studies targeting Hispanic women at
      risk of depression in pregnancy.

PMID- 20824319
TI  - Violence and other stressful life events as triggers of depression and anxiety:
      what psychosocial resources protect African American mothers?
AB  - Understanding the risk and protective factors related to maternal mental health
      problems is important for improving the well-being of mothers and children,
      particularly in African American populations which may be at greater risk for
      maternal depression and resulting child behavior problems. This study explored
      whether three psychosocial resources--emotional resilience, social support, and
      ethnic identity--serve as protective factors in the face of specific stressful
      events that may trigger African American mothers' depression and anxiety
      symptoms. Standard self-report measures of depression, anxiety, negative life
      events, community violence, abuse, emotional resilience, social support, and
      ethnic identity were administered to African American mothers (N=209) of 2-18
      month-old children. Linear regression models revealed main effects of negative
      life events and abuse on increased depression and anxiety symptoms, while
      emotional resilience and social support predicted decreased symptoms. There was
      also a significant interaction revealing a protective-reactive effect of ethnic
      identity on the associations of witnessed community violence with depression and
      anxiety symptoms. It is important for primary care providers to screen African
      American mothers for negative life events and abuse to identify those at
      increased risk for maternal depression and anxiety symptoms. Treatment programs
      should target emotional resilience, enhanced social support, and stronger ethnic
      group affiliation, which may be most effective at preventing mental health
      problems among mothers exposed to relative lower levels of community violence.

PMID- 20824321
TI  - Wanted: a theoretical roadmap to research and practice across individual,
      interpersonal, and structural levels of analysis.

PMID- 20824320
TI  - Evaluation of Syracuse Healthy Start's program for abnormal flora management to
      reduce preterm birth among pregnant women.
AB  - Randomized trials of bacterial vaginosis (BV) treatment among pregnant women to
      reduce preterm birth have had mixed results. Among non-pregnant women, BV recurs
      frequently after treatment. Randomized trials of early BV treatment for pregnant
      women in which recurrence was retreated have shown promise in reducing preterm
      birth. Syracuse's Healthy Start (SHS) program began in 1997; in 1998 prenatal
      care providers for pregnant women living in high infant mortality zip codes were
      encouraged to screen for abnormal vaginal flora at the first prenatal visit.
      Vaginal swabs were sent to a referral hospital laboratory for Gram staining and
      interpretation. SHS encouraged providers to treat and rescreen women with
      bacterial vaginosis or abnormal flora (BV). We abstracted prenatal and hospital
      charts of live births between January 2000 and March 2002 for maternal conditions
      and treatments. We merged abstracted data with local electronic data. We
      evaluated the effect of BV screening before 22 weeks gestation, treatment, and
      rescreening using a retrospective cohort study design. Among 838 women first
      screened before 22 weeks, 346 (41%) had normal flora and 492 (59%) women had BV
      at a mean of 13 weeks gestation; 202 (24%) did not have treatment documented and
      290 (35%) received treatment at a mean of 15 weeks gestation; 267 (92%) of those
      treated were re-screened. Among pregnant women with early BV, 42 (21%) untreated
      women and 28 (10%) treated women delivered preterm (Odds Ratio [OR] 0.4, 95%
      confidence interval [CI] 0.2-0.7)). After adjustment for age, race, prior preterm
      birth and other possible confounders, treatment remained associated with a
      reduced risk of preterm birth compared to no treatment (aOR = 0.5, 95% CI 0.3
      0.9); the aOR for women with normal flora was not significantly different.
      CONCLUSION: Screening, treatment, and rescreening for BV/abnormal flora between
      the first prenatal visit and 22 weeks gestation showed promise in reducing
      preterm births and deserves further study.

PMID- 20824322
TI  - Opinion : how should we define success in assisted reproduction? is live birth
      rate the gold standard measurement?

PMID- 20824323
TI  - How do children with ADHD (mis)manage their real-life dyadic friendships? A multi
      method investigation.
AB  - This multimethod study provides detailed information about the friendships of 87
      children (76% boys) with ADHD and 46 comparison children aged 7-13 years. The
      methods included parent and teacher ratings, self-report measures and direct
      observation of friends' dyadic behaviors in three structured analogue tasks.
      Results indicated that, in contrast with comparison children, children with ADHD
      had friends with high levels of ADHD and oppositional symptoms; they perceived
      fewer positive features and more negative features, and were less satisfied in
      their friendships. Observational data indicated that children with ADHD performed
      both more legal and more illegal maneuvers than comparison children in a fast
      paced competitive game. While negotiating with their friends, children with ADHD
      made more insensitive and self-centered proposals than comparison children. In
      dyads consisting of one child with ADHD and one typically developing child,
      children with ADHD were often more dominant than their friends.

PMID- 20824324
TI  - Semi-quantitative evaluation of estrogen receptor expression is a strong
      predictive factor of pathological complete response after anthracycline-based neo
      adjuvant chemotherapy in hormonal-sensitive breast cancer.
AB  - Absence of hormonal receptors (HR) expression is a predictive factor of high
      pathologic complete response (pCR) rate after neo-adjuvant chemotherapy. However,
      HR-positive tumors are less chemosensitive. In the present study, we evaluated
      the predictive value of estrogen (ER) and progesterone (PgR) semi-quantitative
      expression in patients with HR-positive tumors treated uniformly with
      antracycline-based neoadjuvant chemotherapy without hormonal treatment. Value of
      HR expression as a predictive factor was then evaluated in a multivariate
      analysis with tumor grade, Ki67 index and HER2 expression. From January 2000 and
      December 2006, 177 patients with HR-positive breast ductal invasive carcinoma >=2
      cm in its largest diameter were treated with six cycles of an anthracycline-based
      neo-adjuvant chemotherapy. Tumor grade, ER, PgR, HER2 status and Ki67 index were
      determined on microbiopsy performed before chemotherapy. A semi-quantitative
      evaluation of ER and PgR expression by IHC was performed using the Barnes'score.
      pCR rate was significantly different (P < 0.001) according to the ER expression
      score. pCR rate was 28% for low score, 9% for medium score and 3% for high score.
      On the contrary, pCR rate was not significantly different (P = 0.49) according to
      the PgR expression score. In the multivariate analysis, ER expression score (P =
      0.0002) and Ki67 index (P = 0.02) were the only predictive factors of response
      for HR-positive tumors. pCR after anthracycline-based chemotherapy is
      significantly correlated with the ER expression score.

PMID- 20824325
TI  - Description and evaluation of imposex in Strombus canarium Linnaeus, 1758
      (Gastropoda, Strombidae): a potential bio-indicator of tributyltin pollution.
AB  - Strombus canarium Linnaeus, 1758 is an important gastropod species within the
      study area and was traditionally collected for food by the locals. The objective
      of the present study is to assess the incidence of imposex and its severity in
      this species. Adult conchs were sampled during their main reproductive period,
      from October 2005 to January 2006, at Sungai Pulai estuary, Johor Straits,
      Malaysia. A total of 32.81% of adult females showed imposex characteristics, with
      varying degrees of severity though. The relative penis size (RPS) index ranged
      from 1.74 to 33.29 (mean = 13.40 +/- 2.27, n = 21), while the relative penis
      length (RPL) index ranged from 6.28 to 55.19 (mean = 25.83 +/- 3.33, n = 21). The
      use of vas deferens sequence (VDS) index was however cannot be applied as the
      presence of egg groove obscured any vas deferens development in affected females.
      Sequence of imposex (male penis) development in female conch, from merely a small
      stump to an advance male penis homologous was therefore carefully analyzed and
      described, and an alternative imposex classification scheme was proposed. S.
      canarium can be a good indicator for monitoring of organotin pollution within the
      study area. However, more studies are needed in order to further develop and test
      its validity and application, such as its correlation with levels of pollutant
      within the tissues and the environment, as well as its application on other
      Strombus species.

PMID- 20824326
TI  - Quercus ilex L. carbon sequestration capability related to shrub size.
AB  - CO(2) sequestration capacity of Quercus ilex L., an evergreen species developing
      in shrub and forest communities widely distributed in the Mediterranean Basin,
      was analysed. Experiments were carried out in the period of January to December
      2009 on 20 shrubs of different size, growing at the Botanical Garden of Rome. At
      shrub level, the largest differences concern total photosynthetic leaf surface
      area per shrub and shrub volume. Shrubs structure significantly contribute to
      reduce total irradiance and air temperature below the canopy. Leaf mass per area
      is higher in sun leaves than in shade ones (20 +/- 1 and 12 +/- 2 mg cm( -2),
      respectively). Sun leaves are also characterised by the highest leaf thickness
      (78% higher in sun than in shade leaves), the spongy parenchyma thickness (71%
      higher in sun than in shade leaves) and the highest adaxial cuticle thickness
      (7.2 +/- 1.2 and 4.7 +/- 0.5 MUm, respectively). Net photosynthetic rates (P (N))
      of sun and shade leaves are the highest in spring, and shade leaves contribute 6%
      to the whole shrub P (N). Q. ilex CO(2) sequestration depends on shrub size. In
      particular, the CO(2) sequestration per shrub was 0.20 +/- 0.02 Kg CO(2) year( 
      1) in small shrubs, and it was 75% and 98% lower than in medium and large ones.
      The highest CO(2) sequestration is measured in spring, decreasing 77% during
      drought. Q. ilex may play a significant role in mitigating carbon dioxide
      concentration and lowering air and soil temperature in areas around the
      Mediterranean Basin.

PMID- 20824327
TI  - Possible way to substantial improvement of early warning system in the
      International Odra (Oder) River Basin.
AB  - Water ecosystems are threatened by accidental spills of pollution. Rapidity and
      trueness of information gathering the biological impact of accidental pollution
      is crucial for the efficiency of the minimisation of possible deterioration of
      ecosystems and for success in detecting the source of pollution. Due to the
      randomised occurrence of accidental spills the only way to quickly detect
      hazardous situations is to perform continuous monitoring of surface water
      quality. The current situation in the field of early warning in the International
      Odra (Oder) River basin is not satisfactory. The actual number of monitoring
      stations and list of routinely continuously monitored parameters are not able to
      meet the needs of sensitive and rapid detection of biological impact of
      accidental pollution spills. An effort to change this unfavourable situation was
      the reason for the offer survey, selection and a model operation of a
      commercially produced biological monitoring device. This apparatus was located on
      the border-line profile on the territory of the Czech Republic and represented
      the first and only one tool of continual biological monitoring of surface water
      quality in the International Odra (Oder) River Basin. The selected apparatus was
      the Daphnia Toximeter produced by the firm bbe Moldaenke (Kiel, Germany). This
      device exploited for rapid detection of changes of biological quality of surface
      water evaluation of behavioural response of monitoring organisms-daphnids. Five
      years of model operation proved its suitability for early warning purposes. The
      apparatus was reliable in function and sensitive enough to detect the
      deterioration of the biological quality of the river water. The given examples
      document its applicability not only for detection of accidental spills but also
      of illegal emissions of pollution, which are very often toxic.

PMID- 20824328
TI  - Topographic factor in the groundwater estimations--a case study in typical semi
      arid hard rock environments of Andhra Pradesh.
AB  - Water table fluctuation (deltah) can be used to rapidly assess changes in
      groundwater storage. But deltah gives acceptable results only if the point of
      observation is ideally located in the catchment of interest and gives average
      deltah of the area, a condition which is rarely met. However, if large numbers of
      observation wells are located within a basin (a catchment) the average deltah can
      be computed and used. But, a better way is to use points obtained by shallowest
      water level and deepest water levels to construct a wedge of water table
      fluctuation across the area of interest; the mean height of this wedge can be
      assumed to be the mean deltah in the area. And when there is only one observation
      well, the fact that water table is a subdued replica of the topography, is made
      use to construct the wedge of water table fluctuation. The results from some
      randomly selected observations in typical semi-arid, hard rock environment in
      Andhra Pradesh show that through this approach mean deltah can be effectively
      used to get change in groundwater storage in area. The mean recharge obtained in
      this study is in the order of 75 and mean draft is 58 mm/a, while mean recharge
      and draft obtained by conventional technique are 66 and 54 mm/a, respectively.
      The most likely specific yield around the middle reaches of a catchment ranges
      between 0.012 and 0.041 which is within the range given by Groundwater Estimation
      Committee of India for hard rocks.

PMID- 20824329
TI  - Prevalence of heavy metal resistance in bacteria isolated from tannery effluents
      and affected soil.
AB  - In the present study, a total of 198 bacteria were isolated, 88 from the tannery
      effluents and 110 from agricultural soil irrigated with the tannery effluents.
      Tannery effluents and soils were analyzed for metal concentrations by atomic
      absorption spectrophotometer. The tannery effluents and soil samples were found
      to be contaminated with chromium, nickel, zinc, copper, and cadmium. All isolates
      were tested for their resistance against Cr(6+ ), Cr(3+ ), Ni(2+ ), Zn(2+ ),
      Cu(2+ ), Cd(2+ ), and Hg(2+ ). From the total of 198 isolates, maximum bacterial
      isolates were found to be resistant to Cr(6+ ) 178 (89.9%) followed by Cr(3+ )
      146 (73.7%), Cd(2+ ) 86 (43.4%), Zn(2+ ) 83 (41.9%), Ni(2+ ) 61 (30.8%), and
      Cu(2+ ) 51 (25.6%). However, most of the isolates were sensitive to Hg(2+ ).
      Among the isolates from tannery effluents, 97.8% were resistant to Cr(6+ ) and
      64.8% were resistant to Cr(3+ ). Most of the soil isolates were resistant against
      Cr(6+ ) (83.6%) and Cr(3+ ) (81.8%). All isolates were categorized into Gram
      positive and Gram-negative bacteria. In a total of 114 Gram-positive isolates,
      91.2% were resistant to Cr(6+ ) followed by 73.7% to Cr(3+ ), 42.1% to Zn(2+ ),
      40.4% to Cd(2+ ), and 32.5% to Ni(2+ ). Among Gram-negative isolates, 88.1% were
      found showing resistance to Cr(6+ ), 75.0% to Cr(3+ ), and 47.6% were resistant
      to Cd(2+ ). Majority of these metal-resistant isolates were surprisingly found
      sensitive to the ten commonly used antibiotics. Out of 198 isolates, 114 were
      found sensitive to all antibiotics whereas only two isolates were resistant to
      maximum eight antibiotics at a time. Forty-one and 40 isolates which constitute
      20.7% and 20.2% were resistant to methicilin and amoxicillin, respectively.

PMID- 20824330
TI  - Mycotoxin levels and incidence of mould in Turkish rice.
AB  - One hundred unpackaged rice samples, each weighing 500 g, were randomly collected
      at retail stores and open markets in the largest rice growing area (Thrace) in
      Turkey and analysed for mould counts, predominant mould genera, moisture content
      and mycotoxin levels. Mould counts ranged from 1.0 * 10(1) to 1.5 * 10(4) cfu/g
      in 70 of 100 samples, and the correlation between moisture content and mould
      count was significant (p <= 0.05). Aspergillus spp. and Penicillium spp.,
      potential mycotoxin producers, were the dominant moulds. In one area from which
      samples were collected, the mycotoxin content of rice was found to be positively
      correlated with moisture content; samples with higher moisture also contained
      higher numbers of moulds. The levels of total aflatoxins, aflatoxin B1 and
      ochratoxin A were higher than the maximum tolerable limits (4, 2 and 3 MUg/kg,
      according to the EC Regulation and the Turkish Food Codex) for 32, 14 and 30 of
      100 rice samples, respectively. This is the first comprehensive report of
      ochratoxin A levels in rice grown in Thrace, Turkey.

PMID- 20824331
TI  - Mortality factors and lead contamination of wild birds from Korea.
AB  - Wild birds have frequently been found dead in their natural habitats, but little
      is known about what ecological stressors may impact health of wild populations.
      Here, we report the potentially harmful lead (Pb) levels in tissues along with
      necropsies on 69 individuals of cranes, raptors, and waterfowl found dead between
      2000 and 2003 in Korea. In all samples diagnosed, trauma (n = 22), severe
      emaciation (n = 15), and infectious diseases (n = 11) were identified. In the
      survey, injury with Pb shot or bullet fragments was associated with three of the
      deaths; one of three showed lesions suggestive of Pb poisoning in the tissues. Of
      69 birds, 12 had >25 ppm dry wt. (equivalent to 8 ppm wet wt.) in liver or
      kidney, which is known to be a potentially lethal level of Pb in wild birds.
      Three individuals had hepatic Pb levels of 101.3 ppm (Whooper swan), 120.4 ppm
      (Great white-fronted goose), and 1,059 ppm (Mandarin duck), with evidence of Pb
      pellets in their gizzard. This study suggests that many birds examined may be
      suffering from excessive Pb exposure that may be of health concern with respect
      to a potential cause of their mortality. The need for additional research is
      heightened when considering that some migrants are classified as a globally
      protected species by the International Union for the Conservation of Nature.

PMID- 20824332
TI  - Multi-route risk assessment from trihalomethanes in drinking water supplies.
AB  - The main objectives of this study were to investigate the concentration and
      lifetime cancer risk and hazard index of trihalomethanes (THMs) through multiple
      routes like oral ingestion, dermal absorption, and inhalation exposure in the
      water samples collected at water treatment plant endpoints. Bromoform has been
      found in highest concentration followed by chloroform. A lesser concentration of
      dibromochloromethane has been found than dichlorobromomethane in most of the
      studied water, which is an unusual scenario, in spite of the high concentration
      of bromide in the water which can be attributed to the formation, speciation, and
      distribution of THMs in the breakpoint chlorination curve. Among the three
      pathways studied, inhalation contributed 80-90% of the total risk followed by
      oral exposure and dermal contact. Chloroform was found to be the major THM which
      is having cancer risk in its gaseous form whereas bromoform contributed highest
      cancer risk through oral ingestion. The average hazard index of total THMs
      through oral route was higher than unity, indicating high noncarcinogenic risk.
      The discrepancy between the three exposure pathways may be attributed to
      different concentration and speciation of THMs present in the waters. The
      sensitivity analysis by tornado diagram confirmed the highest positive impact of
      chloroform to the total cancer risk and, indirectly, confirmed inhalation as the
      major pathway of exposure. This study suggests the modification of the regulatory
      issues related to THMs based on the health risk associated with each THM and
      exposure pathway.

PMID- 20824333
TI  - Quantification of triazine herbicides in soil by microwave-assisted extraction
      and high-performance liquid chromatography.
AB  - A method for the determination of herbicides residues, triazine (atrazine,
      metribuzin, ametryn, and terbutryn), in soil samples with high-performance liquid
      chromatography (HPLC)-UV detection is described. The proposed method is based on
      microwave-assisted extraction (MAE) of soil samples for 4 min at 80% of 850-W
      magnetron outputs in the presence of mixture of solvents
      (methanol/acetonitrile/ethylacetate). Related important factors influencing the
      MAE efficiency, such as the solvent type and volume, irradiation energy, and
      time, were optimized in detail. Calibration curve ranges established using HPLC
      for metribuzin, atrazine, ametryn, and terbutryn are 1.0-19.0, 0.9-18.0, 0.6
      11.0, and 0.7-11.0 ug mL( -1), respectively. The limits of detection of
      metribuzin, atrazine, ametryn, and terbutryn are 0.30, 0.24, 0.16, and 0.20 ug
      mL( -1) while limits of quantification are 1.0, 0.80, 0.50, and 0.60 ug mL( -1),
      respectively. A Plackett-Burman factorial design was used as a screening method
      in order to select the variables that influence MAE extraction. The recoveries of
      the method at three different spiked levels were assessed by analyzing real soil
      samples and were found to be in the range of 83.33 +/- 0.12-96.33 +/- 0.23 with
      good precision (<8%).

PMID- 20824334
TI  - Investigation of trihalomethanes formation potential in Karoon River water, Iran.
AB  - Organic matters in raw water have a potential to generate harmful disinfection by
      products such as trihalomethanes (THMs) during the chlorination process. The
      objectives of this study were to investigate the trihalomethane formation
      potential (THMFP) in Karoon River water and to determine the effect of several
      factors including total organic carbon (TOC), pH, chlorine dosage, water
      temperature, and seasonal variation. The results showed that, among all factors,
      TOC and water temperature have a remarkable effect on THMFP. The experimental
      results from batch studies indicated that increasing of pH value yielded a
      greater THMFP concentration for Karoon River water. THMFP levels of Karoon River
      water in summer times, when water temperature exceeded 26 degrees C, were 1.2-1.6
      times higher than in the spring and fall seasons, when water temperature was
      below 15 degrees C. It was found that the measured THMFP at Karoon River water in
      the spring and fall seasons were very rarely higher than 100 MUg/L.

PMID- 20824335
TI  - Accumulation of nitrogen and changes in assimilation pigments of lichens
      transplanted in an agricultural area.
AB  - The results of a survey aimed at testing the hypothesis that the lichen Evernia
      prunastri, when transplanted in an agricultural area with high atmospheric NH(3)
      concentrations, would respond to NH(3) air pollution accumulating nitrogen in its
      thalli and showing changes in the concentration of assimilation pigments are
      presented. The results confirmed the hypothesis and showed that all lichen
      transplants accumulated nitrogen, suggesting that besides the release of
      atmospheric ammonia by animal stockfarms, the use of N-based fertilizers and the
      deposition of N-rich dust also may contribute to the high nitrogen availability
      to lichens in the study area. The result indicated that in the study area both
      the critical level of NH(3) and the critical load of N for lichens are exceeded
      and physiological damage is to be expected in sensitive species. The results of
      assimilation pigments in E. prunastri, with a decrease in the concentration of
      chlorophylls a and b and carotenoids, as well as chlorophyll degradation to
      phaeophytin, confirmed this hypothesis. However, owing to the limited data set
      and pending further studies, these conclusions should be considered as limited to
      the study area.

PMID- 20824336
TI  - Monitoring urban expansion and land use/land cover changes of Shanghai
      metropolitan area during the transitional economy (1979-2009) in China.
AB  - This study explored the spatio-temporal dynamics and evolution of land use/cover
      changes and urban expansion in Shanghai metropolitan area, China, during the
      transitional economy period (1979-2009) using multi-temporal satellite images and
      geographic information systems (GIS). A maximum likelihood supervised
      classification algorithm was employed to extract information from four landsat
      images, with the post-classification change detection technique and GIS-based
      spatial analysis methods used to detect land-use and land-cover (LULC) changes.
      The overall Kappa indices of land use/cover change maps ranged from 0.79 to 0.89.
      Results indicated that urbanization has accelerated at an unprecedented scale and
      rate during the study period, leading to a considerable reduction in the area of
      farmland and green land. Findings further revealed that water bodies and bare
      land increased, obviously due to large-scale coastal development after 2000. The
      direction of urban expansion was along a north-south axis from 1979 to 2000, but
      after 2000 this growth changed to spread from both the existing urban area and
      along transport routes in all directions. Urban expansion and subsequent LULC
      changes in Shanghai have largely been driven by policy reform, population growth,
      and economic development. Rapid urban expansion through clearing of vegetation
      has led to a wide range of eco-environmental degradation.

PMID- 20824337
TI  - Phytoplankton distribution across the southeast Adriatic continental and shelf
      slope to the west of Albania (spring aspect).
AB  - We present the first insight to the oceanography of the southeastern Adriatic
      Sea, where coastal water influenced by Albanian rivers comes into contact with
      the inflowing oligotrophic Eastern Adriatic Current (Ionian Surface Water and
      Levantine Intermediate Water). A distinct plankton distribution was observed on
      each side of the shelf break hydrographic boundary in May 2009, during gradual
      warming of the surface waters. The prochlorophytes accumulated along the
      nutricline above the shelf and continental slope. The phosphorus limited inshore
      waters were dominated by a small diatom Chaetoceros circinalis, dinoflagellates,
      cryptophytes, autotrophic picoplankton, and heterotrophic nanoplankton. The
      offshore surface layer was characterized by bigger nanoplankton
      (coccolithophorids, green flagellates). Low nutrient concentrations influence
      relatively low productivity not only above the Albanian shelf but also further to
      the north along the Montenegrine and Croatian coastal Adriatic Sea.

PMID- 20824338
TI  - Characteristics of assaultive psychiatric patients: 20-year analysis of the
      Assaultive Staff Action Program (ASAP).
AB  - Empirical research demonstrates that patient assaults on staff are a worldwide
      occupational hazard. This study examined patient assailant characteristics in a
      20-year longitudinal, retrospective study in one public health care system. Older
      male patients with schizophrenic illness and histories of violence toward others
      and substance use disorder and younger male/female patients with personality
      disorders and histories of violence toward others, personal victimization, and
      substance use disorder were the more frequent assailants. This was true at 10-,
      15-, and 20-year periods. Specific clinical findings with regard to forensic
      patients, the violence triad, and victimization of women as well as
      methodological issues were discussed and the implications noted.

PMID- 20824339
TI  - Adolescents' perspectives about brief psychiatric hospitalization: what is
      helpful and what is not?
AB  - Significant numbers of adolescents receive inpatient psychiatric services, yet we
      know little about their experiences: what about hospitalization is perceived as
      helpful and what is counter-productive or even harmful? In this study, eighty
      adolescents hospitalized for the first time in a psychiatric program were
      interviewed within a week of discharge (using a semi-structured interview
      format), and asked to describe what did and did not help them. Multiple themes
      emerged relating to helpful experiences and these were grouped in three
      categories: interpersonal support, therapy and psycho-education, and environment;
      Unhelpful/harmful experiences were classified in four categories: rigidity and
      confinement, lack of treatment responsiveness, frightening/anxiety-provoking
      experiences, and other. Participants provided rich feedback that both reinforces
      existing practices and offers ways for programs to change practices to better
      meet adolescents' developmental needs. Some factors noted as key therapeutic
      ingredients, especially the helpful role of peers, have not previously been
      included in hospital satisfaction surveys.

PMID- 20824340
TI  - MEG connectivity analysis in patients with Alzheimer's disease using cross mutual
      information and spectral coherence.
AB  - Alzheimer's disease (AD) is an irreversible brain disorder which represents the
      most common form of dementia in western countries. An early and accurate
      diagnosis of AD would enable to develop new strategies for managing the disease;
      however, nowadays there is no single test that can accurately predict the
      development of AD. In this sense, only a few studies have focused on the
      magnetoencephalographic (MEG) AD connectivity patterns. This study compares brain
      connectivity in terms of linear and nonlinear couplings by means of spectral
      coherence and cross mutual information function (CMIF), respectively. The
      variables defined from these functions provide statistically significant
      differences (p < 0.05) between AD patients and control subjects, especially the
      variables obtained from CMIF. The results suggest that AD is characterized by
      both decreases and increases of functional couplings in different frequency bands
      as well as by an increase in regularity, that is, more evident statistical
      deterministic relationships in AD patients' MEG connectivity. The significant
      differences obtained indicate that AD could disturb brain interactions causing
      abnormal brain connectivity and operation. Furthermore, the combination of
      coherence and CMIF features to perform a diagnostic test based on logistic
      regression improved the tests based on individual variables for its robustness.

PMID- 20824341
TI  - An automatic segmentation method for regional analysis of femoral neck images
      acquired by pQCT.
AB  - We developed an automatic method for regional analysis of femoral neck images
      acquired by peripheral quantitative computed tomography (pQCT), based on
      automatic spatial re-alignment and segmentation; the segmentation method, based
      on a morphological approach, explicitly accounts for the presence of three
      different bone compartments: cortical region, trabecular region, and transition
      zone between cortical and trabecular compartments. The proposed method was
      applied on 13 femoral neck sections derived from female donors who were
      undergoing hip replacement surgery for primary degenerative arthritis or
      fracture, and a typical densitometric and structural analysis was performed both
      globally and regionally. The proposed segmentation method was quantitatively
      evaluated by comparing automatic contour and the corresponding manual contours
      delineated by three operators using metrics based on surface distance (average
      symmetric distance, ASD) and volumetric overlapping (dice similarity coefficient,
      DSC). The same approach was used to validate the automatic spatial orientation,
      considering as metric the difference between manual and automatic angle
      orientation. Results confirm a satisfactory agreement between automatic and
      manual performances (ASD < 0.41 mm, DSC > 0.91, orientation difference = 3.61
      degrees ) and show that globally our algorithm performs very well. Concerning
      regional analysis application, from our results we can observe that significant
      differences are present among the four bone quadrants.

PMID- 20824342
TI  - Impact of pregnancy and vaginal delivery on the passive and active mechanics of
      the rat vagina.
AB  - Remodeling of vaginal extracellular matrix and smooth muscle likely plays a
      critical role in reducing the risk of maternal injury during vaginal delivery by
      altering the mechanical properties to increase distension and reduce stress. Long
      Evans rats were divided into five groups to examine the passive mechanical and
      active contractile properties throughout pregnancy and postpartum: virgin (n=17),
      mid-pregnant (Day 14-16, n=12), late-pregnant (Day 20-22, n=14), immediate
      postpartum (0-2 h after delivery, n=14), and 4 week postpartum (n=15).
      Longitudinal sections of vaginal tissue were loaded to failure uniaxially for
      passive mechanical or active contractile properties were examined. For passive
      mechanics, the tangent modulus decreased 45% by mid-pregnancy and immediately
      postpartum (p<0.001). The ultimate strain continuously increased up to 43% higher
      than virgin animals (p=0.007) in the immediate postpartum group. For active
      mechanics, the maximal contractile force was 36-56% lower through immediate
      postpartum animals, and was significantly more sensitive to K+ throughout
      pregnancy and postpartum (p=0.003). The changes observed in the passive and
      active properties of the rat vagina are consistent with what would be expected
      from a tissue that is remodeling to maximize its ability to distend at the time
      of vaginal delivery to facilitate passage of the fetus with minimal injury.

PMID- 20824343
TI  - A wireless system for monitoring transcranial motor evoked potentials.
AB  - Intraoperative neurophysiological monitoring (IONM) is commonly used as an
      attempt to minimize neurological morbidity from operative manipulations. The goal
      of IONM is to identify changes in the central and peripheral nervous system
      function prior to irreversible damage. Intraoperative monitoring also has been
      effective in localizing anatomical structures, including peripheral nerves and
      sensorimotor cortex, which helps guide the surgeon during dissection. As part of
      IONM, transcranial motor evoked potentials (TcMEPs), and somatosensory evoked
      potentials (SSEPs) are routinely monitored. However, current wired systems are
      cumbersome as the wires contribute to the crowded conditions in the operating
      room and in doing so not only it limits the maneuverability of the surgeon and
      assistants, but also places certain demand in the total anesthesia required
      during surgery, due to setup preoperative time needed for proper electrode
      placement, due to the number and length of the wires, and critical identification
      of the lead wires needed for stimulation and recording. To address these
      limitations, we have developed a wireless TcMEP IONM system as a first step
      toward a multimodality IONM system. Bench-top and animal experiments in rodents
      demonstrated that the wireless method reproduced with high fidelity, and even
      increased the frequency bandwidth of the TcMEP signals, compared to wired
      systems. This wireless system will reduce the preoperative time required for IONM
      setup, add convenience for surgical staff, and reduce wire-related risks for
      patients during the operation.

PMID- 20824344
TI  - Influences of acid-treated multiwalled carbon nanotubes on fibroblasts:
      proliferation, adhesion, migration, and wound healing.
AB  - With the increasing applications of carbon nanotubes (CNTs) in fields of
      biomedical engineering and medical chemistry, it is important to understand the
      response of mammalian cells to the CNTs exposure and treatment. In this study,
      the influences of multiwalled carbon nanotubes (MWCNTs) on cellular behavior of
      human dermal fibroblasts and NIH 3T3 murine fibroblasts were investigated.
      Results showed that the MWCNTs treatment induced dose-dependent cytotoxicity and
      arrested the cell cycle in the G1 phase, indicating inhibition of DNA synthesis.
      The presence of MWCNTs also down regulated the expression level of adhesion
      related genes, and simultaneously caused cytoskeleton damage and disturbance of
      actin stress fibers, thereby inducing dramatically adverse effects on the cell
      physiological functions such as cell spreading, adhesion, migration, and wound
      healing ability.

PMID- 20824345
TI  - Pathophysiology of fatty acid oxidation disorders.
AB  - Mitochondrial fatty acid oxidation represents an important pathway for energy
      generation during periods of increased energy demand such as fasting, febrile
      illness and muscular exertion. In liver, the primary end products of the pathway
      are ketone bodies, which are released into the circulation and provide energy to
      tissues that are not able to oxidize fatty acids such as brain. Other tissues,
      such as cardiac and skeletal muscle are capable of direct utilization of the
      fatty acids as sources of energy. This article provides an overview of the
      pathogenesis of fatty acid oxidation disorders. It describes the different tissue
      involvement with the disease processes and correlates disease phenotype with the
      nature of the genetic defect for the known disorders of the pathway.

PMID- 20824346
TI  - Phenylketonuria as a model for protein misfolding diseases and for the
      development of next generation orphan drugs for patients with inborn errors of
      metabolism.
AB  - The lecture dedicated to Professor Horst Bickel describes the advances,
      successes, and opportunities concerning the understanding of the biochemical and
      molecular basis of phenylketonuria and the innovative treatment strategies
      introduced for these patients during the last 60 years. These concepts were
      transferred to other inborn errors of metabolism and led to significant reduction
      in morbidity and to an improvement in quality of life. Important milestones were
      the successful development of a low-phenylalanine diet for phenylketonuria
      patients, the recognition of tetrahydrobiopterin as an option to treat these
      individuals pharmacologically, and finally market approval of this drug. The work
      related to the discovery of a pharmacological treatment led metabolic researchers
      and pediatricians to new insights into the molecular processes linked to
      mutations in the phenylalanine hydroxylase gene at the cellular and structural
      level. Again, phenylketonuria became a prototype disorder for a previously
      underestimated but now rapidly expanding group of diseases: protein misfolding
      disorders with loss of function. Due to potential general biological mechanisms
      underlying these disorders, the door may soon open to a systematic development of
      a new class of pharmaceutical products. These pharmacological chaperones are
      likely to correct misfolding of proteins involved in numerous genetic and
      nongenetic diseases.

PMID- 20824347
TI  - Health-related quality of life in haematopoietic stem cell transplant survivors:
      a qualitative study on the role of psychosocial variables and response shifts.
AB  - PURPOSE: Psychosocial assessment prior to haematopoietic stem cell transplants
      (HSCT) can help to identify patients at risk of impaired health-related quality
      of life (HRQOL) post-transplant. According to the response-shift model, certain
      antecedents and mechanisms, along with changes in internal standards, values or
      conceptualizations of HRQOL, facilitate adjustment to changes in health
      circumstances. This study sought to explore the role of psychosocial variables in
      adjustment to compromised HRQOL following HSCT, from the theoretical basis of the
      response-shift model. METHODS: Semi-structured interviews were conducted with 28
      patients (15 women, 13 men; 22-71 years), post-HSCT. Time since transplant ranged
      from 1 month to 28 years. Verbatim transcripts were analysed using template
      analysis. RESULTS: Patients provided narrative examples of changing their values
      and internal standards. Optimism, social support, social comparisons, changing
      expectations and setting goals were identified as important in managing threats
      to HRQOL. CONCLUSIONS: The response-shift model is a useful theoretical basis for
      exploring HRQOL in HSCT patients. Response shifts and psychosocial variables may
      help patients to cope and enabling them to experience good HRQOL despite the
      negative effects of HSCT. Understanding the adjustment processes has implications
      for patient care.

PMID- 20824348
TI  - Linking organ donors and the medical/scientific research community: a US
      perspective.
AB  - The International Institute for the Advancement of Medicine (IIAM) provides non
      transplantable organs and tissues for medical and scientific research, education,
      and drug & device development. The benefits of using human organs and tissues for
      research are vast, and donating for research provides donor families with a
      valuable option if their loved one's organs are unsuitable for transplantation.
      The use of these organs and tissues enables the faster development of more
      efficacious drugs with improved safety profiles, and enhanced understanding of
      basic disease processes that directly affect humans. Human organs and tissues
      offer unique advantages over the use of animal organs and tissues as it is human
      diseases and conditions which we seek to treat, and so logically the results can
      be more directly applied. The added advantage of accessing non-transplantable,
      human organs is that they are in superb condition, and so experiments can be
      conducted in a very physiologically-relevant system. Although the US is a
      sizeable country with a large population and individual regulations governing
      human tissue collection and usage for each of the 50 states comprising the US
      this article will discuss how IIAM succeeds in immediately linking organ donors
      and qualified researchers, ultimately to the great benefit of patients.

PMID- 20824349
TI  - The use of functional human tissues in drug development.
AB  - Fresh, functional human tissues have long been considered the closest possible
      model of human in vivo function and can be used to measure a wide range of
      pharmacological responses. Despite this, relatively little drug development is
      conducted using fresh human tissue because of the logistical and ethical
      difficulties surrounding the availability of tissue and practicalities of
      experimental work. Most tests of drug activity require a living test system
      comprising cells, tissues or whole organisms. In some instances, "living" (fresh)
      human tissues have the potential to reduce or replace animal tests through
      superior prediction of drug safety and efficacy. Before functional human tissue
      tests become a routine part of drug development, two factors must co-exist.
      Firstly, organisations such as Biopta must continue to create compelling evidence
      that human tissues are more predictive than alternative models; such evidence
      will drive demand from the pharmaceutical industry for human tissue-based tests.
      Secondly, the vast number of tissues and organs residual to surgery or unsuitable
      for transplant must be routinely consented for medical research and made
      available to all researchers in an equitable and timely manner. This requires a
      concerted effort throughout the NHS and consistent demand as well as financial
      support from researchers, particularly within industry. It is our view that the
      next 5-10 years will generate compelling evidence of the value of functional
      human tissue-based tests and recognition that more efficient use of residual or
      non-transplantable tissues and organs is an urgent priority for the development
      of new medicines.

PMID- 20824350
TI  - Tissue banking for research: connecting the disconnected.
AB  - Delivering the promise of personalised medicine is the challenge that the current
      generation of scientists face. The variations in human physiology and disease are
      considerable, and designing appropriate strategies to deliver what has been
      promised will require access to tissue from a large number of volunteers. The NHS
      provides an ideal infrastructure for sample acquisition, but requires two things
      to make this available-public consent and support for extra manpower and
      administration. There is a disconnection between the NHS and tissue based
      research that needs to be addressed on a number of levels to provide a
      translational platform. This should enable the path to be beaten to provide the
      ideal tailored treatment for future patients; one that preserves quality of life
      by curing the disease with minimal side effects.

PMID- 20824351
TI  - Pathology: coming in from the cold.
AB  - Following the UK's organ retention scandals that occurred a decade ago,
      politicians unleashed a deluge of well-intentioned but naive and unnecessarily
      burdensome regulations that have progressively stymied human tissue-based
      research, stifling development of improved diagnostic and prognostic tests as
      well as discovery of new treatments based on sound knowledge of human-specific
      biology. For the UK to maintain a leading role in medical research, more sensible
      levels of regulation need to be introduced that recognise differences between
      tissue from donors who have passed-away and surgical tissue that is surplus to
      diagnostic requirements and that otherwise will be incinerated. While it is
      important to reassure the public that research using their tissues will be
      conducted within an approved ethical framework, it is equally important to ensure
      that, as hospital staff and academic researchers, we are able to fulfil our
      unwritten covenant with patients to do our utmost to seek better diagnostic
      assays and more predictive prognostic indicators, while collaborating with our
      colleagues in academia and industry and hence bring hope to patients with
      illnesses for which no effective treatments are yet available. There is a clear
      case for introducing an opt-out system as the default to allow all surplus
      surgical tissues to be immediately available for research, concomitant with an
      education campaign. This is the optimal and most ethical approach to ensure the
      wishes of the vast majority of patients are respected by allowing their residual
      surgical tissues and relevant clinical information to be made available for
      research without the current levels of obstruction and hindrance.

PMID- 20824352
TI  - The current limitations on tissue banking from an academic perspective.
AB  - For research on human physiology and pathologies the most relevant results come
      from human tissue, necessitating the creation of more tissue banks. This need is
      acknowledged by academics, clinical researchers and the pharmaceutical industry.
      For academics, the major obstacles to establishing tissue banks are the somewhat
      cumbersome ethical procedures, a perceived lack of demand for human tissue and
      insufficient knowledge about supply and its demographic differences. The causes
      are inter-related: confusing and time-consuming ethics applications cause some
      researchers to avoid human tissue work and expend research efforts on animal
      studies, leading to a false presumption of a lower level of demand for human
      tissue. Lack of knowledge about why rates of donation are low, and why there are
      differences in donation for different organs, leads to an uncertainty about
      supply. This too poses a problem for tissue bank establishment, and further
      research into this area is required.

PMID- 20824353
TI  - Tissue banking for research--bench to bedside and back--myth, reality or fast
      fading reality at the dawn of a personalised healthcare era.
AB  - In this article, the current landscape where bio-resource based research
      underpins a future paradigm of personalised healthcare is explored and important
      issues are highlighted. Barriers, challenges and needs are described and suggest
      a need for re-structuring, resourcing and investment to increase user
      friendliness in the clinical setting for future gains, while safeguarding the
      patient.

PMID- 20824354
TI  - Access to organs and tissues for research from the organ donor pool within the
      UK.
AB  - The donor organ transplant scenario offers one potential route to access high
      quality human organs and tissues for research. There are well-established
      networks for co-ordinating organ donation events across many countries, including
      the UK, which include robust mechanisms for obtaining consent for ethically
      approved research. Within the UK, the challenge for the next few years is to
      facilitate this research donation with respect to regulatory pathways directed by
      the Human Tissue Act, which covers all aspects of access to human tissues.

PMID- 20824355
TI  - Human lung tissue engineering: a critical tool for safer medicines.
AB  - In the field of human tissue-engineering, there has been a strong focus on the
      clinical aspects of the technology, i.e. repair, replace and enhance a given
      tissue/organ. However, much wider applications for tissue engineering (TE) exist
      outside of the clinic that are often not recognised, and include engineering more
      relevant models than animals in basic research and safety testing. Traditionally,
      research is initially conducted on animals or cell lines, both of which have
      their limitations. With regard to cell lines, they are usually transformed to
      enable indefinite proliferation. These immortalised cell lines provide the
      researcher with an almost limitless source of material. However, the pertinence
      of the data produced is now under scrutiny, with the suggestion that some
      historical cell lines may not be the cell type originally reported. By
      engineering normal, biomimetic (i.e. life-mimicking), human tissues with defined
      physiology (i.e. human tissue equivalents), the complex 3-dimensional (3-D)
      tissue/organ physiology is captured in vitro, providing the opportunity to
      directly replace the use of animals in research/testing with more relevant
      systems. Therefore, it is imperative that testing strategies using organotypic
      models are developed that can address the limitations of current animal and
      cellular models and thus improve drug development, enabling faster delivery of
      drugs which are safer, more effective and have fewer side effects in humans.

PMID- 20824356
TI  - Ethical tissue: a not-for-profit model for human tissue supply.
AB  - Following legislative changes in 2004 and the establishment of the Human Tissue
      Authority, access to human tissues for biomedical research became a more onerous
      and tightly regulated process. Ethical Tissue was established to meet the growing
      demand for human tissues, using a process that provided ease of access by
      researchers whilst maintaining the highest ethical and regulatory standards. The
      establishment of a licensed research tissue bank entailed several key criteria
      covering ethical, legal, financial and logistical issues being met. A wide range
      of stakeholders, including the HTA, University of Bradford, flagged LREC,
      hospital trusts and clinical groups were also integral to the process.

PMID- 20824357
TI  - Proceedings of the human tissues conference, House of Lords, 20 October 2009:
      introduction.
AB  - On 20 October 2009, scientists and politicians gathered in the House of Lord to
      discuss the barriers medical researchers face when attempting to access surplus
      human tissues. Presently, such tissues, including those surplus to requirements
      for diagnosis after surgery, are all too often incinerated because patients'
      permission has not been sought for them to be used in medical research. A similar
      situation arises where organs which have been donated for transplant are
      unsuitable for donation. As a consequence of the conference, the Human Tissues
      Working Party was established to enable the discussions which began so fruitfully
      at the conference to continue, and to allow delegates, and participants who have
      joined subsequently, to present a unified case in submissions to public
      consultations, for example.

PMID- 20824358
TI  - The use of human tissue in drug discovery.
AB  - Experiments conducted on human tissue samples are a key component of modern drug
      discovery programs and complement the use of animal tissue based assays in this
      process. Such studies can (i) enhance our understanding of disease
      pathophysiology, (ii) increase (or decrease) confidence that modulating the
      function of particular molecular targets will have therapeutic benefit (iii)
      allow comparison of the activities of different agents on particular
      mechanisms/processes and (iv) provide information on the potential safety risks
      associated with targets. All of this information is critical in identifying the
      targets that are most likely to deliver efficacious and safe medicines to address
      unmet clinical needs. With the introduction of new technologies, human tissue
      samples are also increasingly being incorporated into drug project screening
      cascades, including their use in high throughput assays. Improved access to human
      tissue would undoubtedly further extend the utility of this valuable resource in
      the drug discovery process.

PMID- 20824359
TI  - Retention and ongoing participation in residential substance abuse treatment:
      perspectives from adolescents, parents and staff on the treatment process.
AB  - Many adolescents entering substance abuse treatment do not stay for the full
      course of prescribed treatment. There have been few explorations into what
      facilitates the ongoing participation of adolescents while in treatment. This
      paper describes adolescent, parent, and treatment staff perceptions of the
      barriers and facilitators to retention and participation. Interviews were
      conducted with 87 adolescents, parents, and staff from three residential
      substance abuse treatment agencies in two states. Data were coded thematically
      and organized into themes by respondent type. Respondents reported barriers
      related to treatment population, program design, and communication and
      relationships, and reported facilitators related only to communication and
      relationships. Staff reported far more barriers than facilitators in comparison
      to either adolescents or parents. Findings suggest that parents and staff
      underestimate their contributions to the treatment process and practitioners
      might benefit from rethinking how to communicate the value of these stakeholders.

PMID- 20824360
TI  - Update in women's health for the general internist.

PMID- 20824361
TI  - Behaviorally defined patient-centered communication--a narrative review of the
      literature.
AB  - BACKGROUND: Touted by some as reflecting a better medical model and cited by the
      influential IOM report in 2000 as one of the six domains of quality care, patient
      centered medicine has yet to fully establish its scientific attributes or to
      become mainstream. One proposed reason is failure to behaviorally define what the
      term 'patient-centered' actually means. OBJECTIVES: (1) To identify patient
      centered articles among all reported randomized controlled trials (RCT); (2) to
      identify those with specific behaviorally defined interventions; (3) to identify
      commonalities among the behavioral definitions; and (4) to evaluate the
      relationship of the well-defined RCTs to patient outcomes. DATA SOURCES: Medline
      from April 2010 to 1975. ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS:
      RCTs having any specific, behaviorally defined patient-centered skill(s) in an
      intervention with some patient outcome involving real adult patients and
      providers in real clinical situations. APPRAISAL AND SYNTHESIS METHODS: Critical
      appraisal via narrative review. RESULTS: The prevalence of any mention of patient
      centeredness among 327,219 RCTs was 0.50% (1,475 studies), from which we
      identified only 13 studies (0.90%) where there were behaviorally-defined patient
      centered skills in an intervention. Although there were too few studies to make
      clinical recommendations, we identified common features of the behavioral
      definitions used: all went well beyond identifying individual skills. Rather,
      skills were grouped, prioritized, and sequenced by virtually all, often
      describing a stepwise patient-centered approach to, variously, gather data,
      address emotions, or inform and motivate. LIMITATIONS: The inherent subjectivity
      of our method for identifying behaviorally-defined studies could under- or over
      represent truly replicable such studies considerably. Also, studies were few and
      very heterogeneous with interventions of widely differing intensity and foci.
      CONCLUSIONS AND IMPLICATIONS: RCTs identified as patient-centered were rare, and
      <1% of these were behaviorally defined and, therefore, possibly replicable. There
      were many common behavioral definitions in the studies reported, and these can
      guide us in identifying agreed-upon patient-centered interventions, the immediate
      next-step in advancing the field.

PMID- 20824362
TI  - Coronary risk assessment by point-based vs. equation-based Framingham models:
      significant implications for clinical care.
AB  - BACKGROUND: US cholesterol guidelines use original and simplified versions of the
      Framingham model to estimate future coronary risk and thereby classify patients
      into risk groups with different treatment strategies. We sought to compare risk
      estimates and risk group classification generated by the original, complex
      Framingham model and the simplified, point-based version. METHODS: We assessed
      2,543 subjects age 20-79 from the 2001-2006 National Health and Nutrition
      Examination Surveys (NHANES) for whom Adult Treatment Panel III (ATP-III)
      guidelines recommend formal risk stratification. For each subject, we calculated
      the 10-year risk of major coronary events using the original and point-based
      Framingham models, and then compared differences in these risk estimates and
      whether these differences would place subjects into different ATP-III risk groups
      (<10% risk, 10-20% risk, or >20% risk). Using standard procedures, all analyses
      were adjusted for survey weights, clustering, and stratification to make our
      results nationally representative. RESULTS: Among 39 million eligible adults, the
      original Framingham model categorized 71% of subjects as having "moderate" risk
      (<10% risk of a major coronary event in the next 10 years), 22% as having
      "moderately high" (10-20%) risk, and 7% as having "high" (>20%) risk. Estimates
      of coronary risk by the original and point-based models often differed
      substantially. The point-based system classified 15% of adults (5.7 million) into
      different risk groups than the original model, with 10% (3.9 million)
      misclassified into higher risk groups and 5% (1.8 million) into lower risk
      groups, for a net impact of classifying 2.1 million adults into higher risk
      groups. These risk group misclassifications would impact guideline-recommended
      drug treatment strategies for 25-46% of affected subjects. Patterns of
      misclassifications varied significantly by gender, age, and underlying CHD risk.
      CONCLUSIONS: Compared to the original Framingham model, the point-based version
      misclassifies millions of Americans into risk groups for which guidelines
      recommend different treatment strategies.

PMID- 20824363
TI  - Pre-operative nomogram to predict risk of peri-operative mortality following
      liver resections for malignancy.
AB  - INTRODUCTION: The majority of liver resections for malignancy are performed in
      older patient with major co-morbidities. There is currently no pre-operative,
      patient-specific method to determine the likely peri-operative mortality for each
      individual patient. The aim of this study was to develop a pre-operative nomogram
      based on the presence of co-morbidities to predict risk of peri-operative
      mortality following liver resections for malignancy. METHODS: The Nationwide
      Inpatient Sample database was queried to identify adult patients that underwent
      liver resection for malignancy. The pre-operative co-morbidities, identified as
      predictors were used and a nomogram was created with multivariate regression
      using Taylor expansion method in SAS software, surveylogistic procedure. Training
      set (years 2000-2004) was utilized to develop the model and validation set (year
      2005) was utilized to validate this model. RESULTS: A total of 3,947 and 972
      patients were included in training and validation sets, respectively. The overall
      actual-observed peri-operative mortality rates for training and validation sets
      were 4.1% and 3.2%, respectively. The decile-based calibration plots for the
      training set revealed good agreement between the observed probabilities and
      nomogram-predicted probabilities. Similarly, the quartile-based calibration plot
      for the validation set revealed good agreement between the observed and predicted
      probabilities. The accuracy of the nomogram was further reinforced by a good
      concordance index of 0.80 with a 95% confidence interval of 0.72 and 0.87.
      CONCLUSIONS: This pre-operative nomogram may be utilized to predict the risk of
      peri-operative mortality following liver resection for malignancy.

PMID- 20824364
TI  - RAGE signaling significantly impacts tumorigenesis and hepatic tumor growth in
      murine models of colorectal carcinoma.
AB  - BACKGROUND: The receptor for advanced glycation end-products (RAGE) is a cell
      surface receptor implicated in tumor cell proliferation and migration. We
      hypothesized that RAGE signaling impacts tumorigenesis and metastatic tumor
      growth in murine models of colorectal carcinoma. MATERIALS AND METHODS:
      Tumorigenesis: Apc (1638N/+) mice were crossed with Rage (-/-) mice in the
      C57BL/6 background to generate Apc (1638N/+)/Rage (-/-) mice. Metastasis: BALB/c
      mice underwent portal vein injection with CT26 cells (syngeneic) and received
      daily soluble (s)RAGE or vehicle. Rage (-/-) mice and Rage (+/+) controls
      underwent portal vein injection with MC38 cells (syngeneic). Rage (+/+) mice
      underwent portal vein injection with MC38 cells after stable transfection with
      full-length RAGE or mock transfection control. RESULTS: Tumorigenesis: Apc
      (1638N/+)/Rage (-/-) mice had reduced tumor incidence, size, and histopathologic
      grade. Metastasis: Pharmacological blockade of RAGE with sRAGE or genetic
      deletion of Rage reduced hepatic tumor incidence, nodules, and burden. Gain of
      function by transfection with full-length RAGE increased hepatic tumor burden
      compared to vector control MC38 cells. CONCLUSION: RAGE signaling plays an
      important role in tumorigenesis and hepatic tumor growth in murine models of
      colorectal carcinoma. Further work is needed to target the ligand-RAGE axis for
      possible prophylaxis and treatment of primary and metastatic colorectal
      carcinoma.

PMID- 20824365
TI  - Prophylactic pancreatectomy for intraductal papillary mucinous neoplasm does not
      negatively impact quality of life: a preliminary study.
AB  - BACKGROUND: Uncertainties remain over whether prophylactic surgery or
      surveillance is the better management option for intraductal papillary mucinous
      neoplasm of the pancreas. The aim of this preliminary study was to determine if
      differences in anxiety and quality of life exist between patients who have
      surgery or undergo surveillance. METHODS: Recruited patients were given the
      Hospital Anxiety and Depression Scale, a general survey that evaluates anxiety,
      and the Functional Assessment of Cancer Therapy-Pancreas, a disease-specific
      survey that assesses quality of life. Questionnaires were scored by standardized
      algorithms and compared using Student's t test or Wilcoxon rank-sum test.
      RESULTS: Sixteen patients had surgery and 16 patients were undergoing
      surveillance. Mean age was 66.8 +/- 19.9 years. Responses from both groups were
      remarkably similar. Surgery patients scored higher on the anxiety questionnaire
      than surveillance patients, although not statistically significant (p = 0.09).
      Surgery patients scored lower on the functional well-being domain of the quality
      of-life instrument (p = 0.03), though there were no differences in overall
      quality of life. CONCLUSION: Prophylactic surgery does not reduce quality of
      life, and a protocol of surveillance does not appear to generate undue anxiety in
      this select patient group. Further investigation with more patients is required
      to validate these findings.

PMID- 20824366
TI  - Pancreaticoduodenectomy can be performed safely in patients aged 80 years and
      older.
AB  - BACKGROUND: Surgery offers the only chance for cure in patients with pancreatic
      cancer, and a growing number of elderly patients are being offered resection. We
      examined outcomes after pancreaticoduodenectomy in patients 80 years and older.
      METHODS: We retrospectively collected data on pancreaticoduodenectomy patients
      from 1992 to 2009 to compare outcomes between patients older and younger than 80
      years. Variables were compared using t-, Wilcoxon rank-sum, or Fisher's exact
      tests. Survival was compared using Kaplan-Meier analysis and log-rank test.
      RESULTS: Patients 80 years and older who underwent pancreaticoduodenectomy were
      similar with respect to sex, race, blood loss, operative times, reoperation,
      length of stay, and readmission compared to younger patients. There were no
      differences in overall complications (47% vs. 51%, p = 0.54), major complications
      (19% vs. 25%, p = 0.25), and mortality (5% vs. 4%, p = 0.53) when comparing older
      to younger patients. In a subset who underwent pancreaticoduodenectomy for ductal
      adenocarcinoma, older patients (n = 45) had a median survival time of 11.6 months
      compared to 18.1 months in younger patients (n = 346; p < 0.01). CONCLUSION:
      Pancreaticoduodenectomy can be performed safely in select patients 80 years and
      older. Age alone should not dissuade surgeons from offering patients resection,
      though elderly patients with pancreatic ductal adenocarcinoma appear to have
      shorter survival than younger patients with the same disease.

PMID- 20824367
TI  - The cholecystokin provocation HIDA test: recreation of symptoms is superior to
      ejection fraction in predicting medium-term outcomes.
AB  - BACKGROUND: The (99m) technetium labelled hepato imino diacetic acid (HIDA) scan
      is widely used in the investigation of patients with typical biliary pain but
      whose trans-abdominal ultrasound scan (US) is normal. Although the standard
      measure by which the HIDA scan is deemed positive is the presence of an ejection
      fraction (EF) of <35% following provocation with cholecystokinin (CCK), there
      still remains debate as to the usefulness of this measure. The aim of this study
      was to compare the roles of EF and symptom provocation following CCK infusion in
      relation to the outcome following laparoscopic cholecystectomy (LC). More
      specifically, we aimed to review the resolution of symptoms for our significant
      population of patients with normal HIDA scan EFs for whom surgery has
      traditionally been deemed inappropriate. PATIENTS AND METHODS: All patients
      undergoing LC for a presumed diagnosis of biliary dyskinesia were identified from
      a prospectively maintained database. Data were collected regarding pre-operative
      symptoms, EF and symptom provocation during the CCK HIDA scan, histological
      findings, early symptomatic outcome, and medium-term follow-up. RESULTS: During
      the period from March 2006 to October 2009, 42 patients with biliary symptoms but
      a negative US were referred for assessment by a single surgeon. There were 31
      women and 11 men with a mean age of 39.0 +/- 12.6 years. All underwent a CCK HIDA
      scan of which 17 were positive with an EF <35% and the remaining 25 were
      negative. All patients reported recreation of symptoms following administration
      of CCK. All gallbladders were delivered intact for histological assessment and
      all but one showed evidence of chronic cholecystitis. At each postoperative
      visit, approximately 2 weeks following the procedure, all patients reported
      resolution of symptoms. After a mean of 18.7 +/- 12.1 months symptom recurrence
      had been noted in only one of 42 (2.4%). CONCLUSIONS: The CCK HIDA scan is a
      useful study in the investigation of acalcalous cholecystitis; however, we would
      suggest that recreation of symptoms following CCK provocation is superior to EF
      for the identification of underlying chronic cholecystitis. Indeed, a normal
      gallbladder ejection fraction does not necessarily rule out a biliary aetiology
      of symptoms for this patient population.

PMID- 20824369
TI  - Solid pseudopapillary tumors of the pancreas. Clinical features, surgical
      outcomes, and long-term survival in 45 consecutive patients from a single center.
AB  - BACKGROUND: Solid pseudopapillary tumors of the pancreas (SPT) are rare
      neoplasms, and the natural history is poorly defined. The aim of this study was
      to define the natural history and compare patient and tumor factors between
      patients with malignant and non-malignant disease. METHODS: Data for all patients
      with SPT who underwent surgical exploration at MSKCC between 1987 and 2009 were
      collected and analyzed. Patient, tumor, treatment, and survival variables were
      examined. Malignant tumors were defined as any tumor that was locally
      unresectable, metastatic, or recurrent. Differences between groups were analyzed
      by Fisher's exact, chi-squared, Wilcoxon, and log-rank tests. RESULTS: Forty-five
      patients had an SPT during the study period. Median age was 38 years (10-63) and
      38 (84%) were women. At the time of diagnosis, 38 were symptomatic, with the most
      common symptom being abdominal pain (n = 35). The most frequent imaging
      characteristic was a solid and cystic tumor (n = 29), most commonly located in
      the tail of the pancreas (n = 23). Resection of the primary tumor (n = 41)
      (41/2,919 = 1.4% of all resections) included distal pancreatectomy in 26,
      pancreatoduodenectomy in 11, central pancreatectomy in two, and enucleation in
      two. Nine patients had malignant disease defined by a locally unresectable tumor
      in three, liver metastases in three, locally unresectable tumor and liver
      metastases in one, local recurrence and liver metastases in one, and local
      recurrence in another. Patients with malignant disease presented with larger
      tumors (7.8 vs. 4.2 cm) (p < 0.005). After median follow-up of 44 months, 34
      patients were without evidence of disease, four patients were alive with disease,
      three patients died of disease, and four patients died of other causes.
      CONCLUSIONS: These results demonstrate that SPT occurs in young women, and the
      majority of patients will experience long-term survival following resection. The
      only feature associated with malignant disease was tumor size at presentation.
      The majority of patients are alive at last follow-up, and a low percentage
      experienced disease recurrence or death from disease.

PMID- 20824368
TI  - Involvement of osteopontin in the matrix-degrading and proangiogenic changes
      mediated by nicotine in pancreatic cancer cells.
AB  - BACKGROUND: Substantial evidence indicates that exposure to cigarette smoke is
      associated with an elevated risk of pancreatic ductal adenocarcinoma (PDA).
      However, the mechanisms underlying the effects of nicotine on the development or
      progression of PDA remain to be investigated. Previously, we showed that nicotine
      promotes the expression of osteopontin c (OPNc), an isoform of OPN protein that
      confers on cancer cells a migratory phenotype. In this study, we explored the
      potential prometastatic role of nicotine in PDA through studying its effect on
      the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial
      growth factor (VEGF) and evaluated the role of OPN in mediating these effects.
      MATERIALS AND METHODS: MMP-9 and VEGF mRNA and protein were analyzed in PDA cells
      treated with or without nicotine (3-300 nM). Transient transfection and
      luciferase-labeled promoter studies evaluated the effects of OPNc and OPN protein
      on the transcription and translation of MMP-9 and VEGF. Real-time PCR and
      immunohistochemistry were used to analyze the mRNA expression levels and
      localization of OPN, MMP-9, and VEGF proteins in matched invasive human PDA and
      surrounding nonmalignant tissues. RESULTS AND DISCUSSION: Nicotine significantly
      enhanced the expression of MMP-9 and VEGF mRNA and protein in PDA cells. Blocking
      OPN with siRNA or OPN antibody prevented the nicotine-mediated increase of both
      MMP-9 and VEGF. Transient transfection of OPNc gene in PDA cells or their
      treatment with recombinant OPN protein significantly (p < 0.05) increased MMP-9
      and VEGF mRNA expression levels and induced their promoter activities. In
      invasive PDA lesions, MMP-9 mRNA levels were significantly (p < 0.005) higher in
      smokers vs. nonsmokers. VEGF protein co-localized with MMP-9 and OPN in the
      malignant ducts and correlated well with their higher levels in invasive PDA
      lesions. CONCLUSIONS: Our data show for the first time that cigarette smoking and
      nicotine may contribute to PDA metastasis through inducing MMP-9 and VEGF and
      suggest that OPN plays a central role in mediating these effects. The presence of
      OPN as a downstream effector of nicotine that is capable of mediating its
      prometastatic effects in PDA cells is novel and could provide a unique
      therapeutic target to control pancreatic cancer aggressiveness, especially in the
      cigarette-smoking population.

PMID- 20824370
TI  - Mesenteric vascular thromboembolism in inflammatory bowel disease: a single
      center experience.
AB  - BACKGROUND: Vascular thrombotic complications in inflammatory bowel disease (IBD)
      are well recognized, although mesenteric vascular thrombotic disease is rare.
      METHODS: We describe nine patients in a tertiary care center with IBD that
      developed thrombosis of the mesenteric arterial or venous vasculature (e.g.,
      mesenteric thrombosis, MT). RESULTS: Eight subjects developed mesenteric venous
      thrombosis (five located in the superior mesenteric vein and three located in a
      branch of the portal vein) and one had a mesenteric arterial embolus, located in
      the splenic artery. Five subjects had Crohn's disease (CD), and four had
      ulcerative colitis. The one subject diagnosed with an arterial thrombosis had CD.
      Mean time from diagnosis of IBD to diagnosis of thrombosis was 24.6 +/- 13.5
      years. Five of the nine subjects developed mesenteric venous thrombosis while
      their IBD was clinically in remission. Seven of nine subjects were symptomatic
      from the development of MT, including bowel infarction that led to development of
      short bowel syndrome. CONCLUSION: Mesenteric thrombosis is a rare complication of
      IBD and may develop during clinical remission, suggesting a potential role for
      factors other than clinically significant inflammation in its pathogenesis.

PMID- 20824371
TI  - National trends in the management and survival of surgically managed gallbladder
      adenocarcinoma over 15 years: a population-based analysis.
AB  - INTRODUCTION: National Comprehensive Cancer Network (NCCN) guidelines recommend
      hepatic resection and lymphadenectomy (LND) for gallbladder adenocarcinoma (GBA).
      We sought to evaluate compliance with these recommendations and to assess trends
      in the management and survival of patients with GBA. METHODS: Using Surveillance,
      Epidemiology and End Results (SEER)-Medicare-linked data, we identified 2,955
      patients with GBA who underwent cancer-directed surgery from 1991 to 2005. We
      assessed clinicopathologic data, trends in surgical management, and survival.
      RESULTS: From 1991 to 2005, preoperative evaluation included CT (62%), MRI (6%),
      and PET (2%). Only 383 (13%) patients underwent radical resection/hepatectomy
      with a temporal increase over the study period (1991-1995, 12%; 1996-1999, 10%;
      2000-2002, 12.0%; 2003-2005, 16%; P < 0.001). For patients undergoing radical
      resection/hepatectomy, LND >= 3 nodes was performed in 96 (3%) patients. Among
      patients who had LND, 47% had nodal metastasis. The overall 1-, 3-, and 5-year
      survival was 56%, 30%, and 21%. On multivariate analysis, radical
      resection/hepatectomy (hazard ratio (HR) = 0.71) and LND >= 3 nodes (HR = 0.56)
      were independently associated with increased survival. There was no significant
      improvement in survival over time (P = 0.60). CONCLUSIONS: Compliance with NCCN
      guidelines for GBA remains poor. Survival of patients with surgically managed GBA
      has not improved over time.

PMID- 20824372
TI  - A systematic review of POSSUM and its related models as predictors of post
      operative mortality and morbidity in patients undergoing surgery for colorectal
      cancer.
AB  - INTRODUCTION: The Physiological and Operative Severity Score for the enUmeration
      of Mortality and morbidity (POSSUM) model and its Portsmouth (P-POSSUM) and
      colorectal (CR-POSSUM) modifications are used extensively to predict and audit
      post-operative mortality and morbidity. This aim of this systematic review was to
      assess the predictive value of the POSSUM models in colorectal cancer surgery.
      METHODS: Major electronic databases, including Medline, Embase, Cochrane Library
      and Pubmed were searched for original studies published between 1991 and 2010.
      Two independent reviewers assessed each study against inclusion and exclusion
      criteria. All data was specific to colorectal cancer surgery. Predictive value
      was assessed by calculating observed to expected (O/E) ratios. RESULTS: Nineteen
      studies were included in final review. The mortality analysis included ten
      studies (4,799 patients) on POSSUM, 17 studies (6,576 patients) on P-POSSUM and
      14 studies (5,230 patients) on CR-POSSUM. Weighted O/E ratios for mortality were
      0.31 (CI 0.31-0.32) for POSSUM, 0.90 (CI 0.88-0.92) for P-POSSUM and 0.64 (CI
      0.63-0.65) for CR-POSSUM. The morbidity analysis included four studies (768
      patients) on POSSUM with a weighted O/E ratio of 0.96 (CI 0.94-0.98).
      CONCLUSIONS: P-POSSUM was the most accurate model for predicting post-operative
      mortality after colorectal cancer surgery. The original POSSUM model was accurate
      in predicting post-operative complications.

PMID- 20824373
TI  - Direct costs of care in a randomized controlled trial of endoscopic sclerotherapy
      versus emergency portacaval shunt for bleeding esophageal varices in cirrhosis-
      Part 4.
AB  - BACKGROUND: Emergency treatment of bleeding esophageal varices (BEV) in cirrhotic
      patients is of prime importance because of the high mortality rate surrounding
      the episode of acute bleeding. Nevertheless, there is a paucity of randomized
      controlled trials of emergency surgical therapy and no reports of the costs of
      any of the widely used forms of emergency treatment. The important issue of
      direct costs of care was examined in a randomized controlled trial that compared
      endoscopic sclerotherapy (EST) to emergency portacaval shunt (EPCS). METHODS: Two
      hundred eleven unselected consecutive patients with ultimately biopsy-proven
      cirrhosis and endoscopically proven acute BEV were randomized to EST (n = 106) or
      EPCS (n = 105). Diagnostic workup was completed, and EST or EPCS was initiated
      within 8 h. Criteria for failure of EST or EPCS were clearly defined, and
      crossover rescue treatment was applied, when primary therapy failed. Ninety-six
      percent of patients underwent more than 10 years follow-up, or until death.
      Complete charges for all aspects of care were obtained continuously for more than
      10 years. RESULTS: Direct charges for all aspects of care were significantly
      lower in patients treated by EPCS than in patients treated by emergency EST
      followed by long-term repetitive sclerotherapy. Charges per patient, per year of
      treatment, and per year in each child's risk class were significantly lower in
      patients randomized to EPCS. Charges in patients who failed endoscopic
      sclerotherapy and underwent a rescue portacaval shunt were significantly higher
      than the charges in both the unshunted sclerotherapy patients and the patients
      randomized to EPCS. This result was particularly noteworthy given the widespread
      practice of using surgical portacaval shunt as rescue treatment only when all
      other forms of therapy have failed. CONCLUSIONS: In this randomized controlled
      trial of emergency treatment of acute BEV, EPCS was significantly superior to EST
      with regard to direct costs of care as reflected in charges for care as well as
      in survival rate, control of bleeding, and incidence of portal-systemic
      encephalopathy. These results provide support for the use of EPCS as a first line
      of emergency treatment of BEV in cirrhosis.

PMID- 20824374
TI  - Predictors of outcome following surgery in colonic perforation: an institution's
      experience over 6 years.
AB  - BACKGROUND: Colonic perforation is associated with abysmal outcome. The aims of
      our study were to review the surgical outcome of patients with perforated colon
      and to identify factors predicting peri-operative complications. METHODS: A
      retrospective review of all patients who underwent surgery for colonic
      perforation from January 2003 to August 2008 was performed. Patients with
      iatrogenic or traumatic perforation were excluded. The severity of abdominal
      sepsis was graded using the Mannheim peritonitis index (MPI). RESULTS: A total of
      129 patients, with median age of 65 years (22-97 years), formed the study group.
      While 29.5% had severe peritoneal contamination, 56.6% had an American Society of
      Anesthesiologists (ASA) score >=3. Sigmoid colon (47.3%) and caecum (24.8%) were
      the most common sites of perforation. Diverticulitis and malignancy were the
      diagnoses in 51.9% and 34.9%, respectively. Hartmann's procedure and right
      hemicolectomy were performed in 43.4% and 34.1% of the patients, respectively.
      Stoma was created in 59.7%. The in-hospital mortality rate in our series was
      15.5%. After multivariate analysis, the independent variables associated with
      worse peri-operative complications were ASA score >=3, MPI >26 and creation of
      stoma. Malignant perforation was associated with higher ASA score and lower
      haematocrit level compared to diverticular perforation. Stoma was created more
      frequently in patients with MPI >26 and left-sided perforation, and was
      associated with worse complications. CONCLUSIONS: Surgery for colonic perforation
      is associated with high morbidity and mortality rates. Short-term outcome is
      determined by ASA score and severity of peritonitis. A lower haematocrit level
      must alert the possibility of malignancy.

PMID- 20824375
TI  - Patient and peri-operative predictors of morbidity and mortality after
      esophagectomy: American College of Surgeons National Surgical Quality Improvement
      Program (ACS-NSQIP), 2005-2008.
AB  - PURPOSE: Our aim was to determine what specific patient and peri-operative
      factors contribute to major complications after esophagectomy. METHODS: Using the
      American College of Surgeons National Surgical Quality Improvement Program
      database, data for esophagectomies between the years 2005 and 2008 were extracted
      and analyzed. Thirty-day post-operative complications were classified into seven
      major groups: (1) wound infections, (2) respiratory complications (pneumonia,
      intubation), (3) cardiac complications, (4) deep venous thrombosis, (5)
      sepsis/septic shock, (6) re-operation, and (7) death. Univariate analysis and
      logistic regression modeling were performed to determine if a significant
      association existed between patient factors or peri-operative factors and these
      post-operative complications. RESULTS: One thousand thirty-two patients who
      underwent esophagectomy were identified. Diabetes was the strongest pre-operative
      independent predictor of death (odds ratio (OR) 10.98; 95% confidence interval
      (CI) 1.37-1.15, p < 0.1) or respiratory (OR 1.86; 95% CI 1.03-3.29, p = 0.04) or
      cardiac (OR 5.14; 95% CI 1.93-13.20, p < 0.01) complications following
      esophagectomy. Thoracotomy performed during the operation was not associated with
      an increased risk of respiratory or cardiac complications. CONCLUSIONS: The major
      predictors of morbidity after an esophagectomy are the patient factors of
      diabetes, dyspnea, peripheral vascular disease, and cerebrovascular accident
      while the peri-operative factors are pre-operative international normalized
      ratio, contaminated wound classification, and American Society of
      Anesthesiologists class. Similarly, the major predictors of mortality are
      diabetes, dyspnea, and age for patient factors and contaminated wound
      classification for peri-operative factors.

PMID- 20824376
TI  - Comparing complications of esophagectomy and pancreaticoduodenectomy and
      potential impact on hospital systems utilizing the accordion severity grading
      system.

PMID- 20824377
TI  - Long-term follow-up after anti-reflux surgery in patients with Barrett's
      esophagus.
AB  - BACKGROUND: Factors associated with the risk of progression of Barrett's
      esophagus remain unclear, and the impact of therapy on this risk remains
      uncertain. The aim of this study was to assess patients followed long-term after
      anti-reflux surgery for Barrett's esophagus. METHODS: A retrospective review was
      performed of all patients with Barrett's who underwent anti-reflux surgery from
      1989 to 2009 and had >=5 years of follow-up. RESULTS: There were 303 patients and
      75 had follow-up >=5 years. Median follow-up time for the 75 patients was 8.9
      years (range 5-18). Regression was seen in 31%. Progression occurred in 8%, and
      these patients were significantly more likely to have a failed fundoplication
      (67% vs. 16%, p = 0.0129). The rate of progression from non-dysplastic Barrett's
      to high-grade dysplasia or cancer was 0.8% per patient year, and was seven times
      higher in patients with a failed fundoplication. CONCLUSION: Compared to the
      accepted rate of progression of non-dysplastic Barrett's to high-grade dysplasia
      or cancer of 1.0% per patient year, anti-reflux surgery reduces this rate during
      long-term follow-up. The rate of progression was significantly lower in patients
      with an intact compared to a disrupted fundoplication, further suggesting that
      anti-reflux surgery can alter the natural history of Barrett's esophagus.

PMID- 20824378
TI  - One hundred thirty resections for pancreatic neuroendocrine tumor: evaluating the
      impact of minimally invasive and parenchyma-sparing techniques.
AB  - BACKGROUND: Increasingly, surgeons apply minimally invasive and parenchyma
      sparing techniques to the management of pancreatic neuroendocrine tumor (PNET).
      The aim of this study was to evaluate the impact of these approaches on patient
      outcomes. METHODS: We retrospectively collected data on patients with PNET and
      compared perioperative and pathologic variables. Survival was analyzed using the
      Kaplan-Meier method. Factors influencing survival were evaluated using a Cox
      proportional hazards model. RESULTS: One hundred thirty patients underwent
      resection for PNET. Traditional resections included 43 pancreaticoduodenectomies
      (PD), 38 open distal pancreatectomies (DP), and four total pancreatectomies.
      Minimally invasive and parenchyma-sparing resections included 25 laparoscopic DP,
      11 central pancreatectomies, five enucleations, three partial pancreatectomies,
      and one laparoscopic-assisted PD. Compared to traditional resections, the
      minimally invasive and parenchyma-sparing resections had shorter hospital stays.
      By univariate analysis of neuroendocrine carcinoma, liver metastases and positive
      resection margins correlated with poor survival. There was an increase in
      minimally invasive or parenchyma-sparing resections over the study period with no
      differences in morbidity, mortality, or survival. CONCLUSION: In this series,
      there has been a significant increase in minimally invasive and parenchyma
      sparing techniques for PNET. This shift did not increase morbidity or compromise
      survival. In addition, minimally invasive and parenchyma-sparing operations
      yielded shorter hospital stays.

PMID- 20824379
TI  - Comparison of outlier identification methods in hospital surgical quality
      improvement programs.
AB  - BACKGROUND: Surgeons and hospitals are being increasingly assessed by third
      parties regarding surgical quality and outcomes, and much of this information is
      reported publicly. Our objective was to compare various methods used to classify
      hospitals as outliers in established surgical quality assessment programs by
      applying each approach to a single data set. METHODS: Using American College of
      Surgeons National Surgical Quality Improvement Program data (7/2008-6/2009),
      hospital risk-adjusted 30-day morbidity and mortality were assessed for general
      surgery at 231 hospitals (cases = 217,630) and for colorectal surgery at 109
      hospitals (cases = 17,251). The number of outliers (poor performers) identified
      using different methods and criteria were compared. RESULTS: The overall
      morbidity was 10.3% for general surgery and 25.3% for colorectal surgery. The
      mortality was 1.6% for general surgery and 4.0% for colorectal surgery. Programs
      used different methods (logistic regression, hierarchical modeling, partitioning)
      and criteria (P < 0.01, P < 0.05, P < 0.10) to identify outliers. Depending on
      outlier identification methods and criteria employed, when each approach was
      applied to this single dataset, the number of outliers ranged from 7 to 57
      hospitals for general surgery morbidity, 1 to 57 hospitals for general surgery
      mortality, 4 to 27 hospitals for colorectal morbidity, and 0 to 27 hospitals for
      colorectal mortality. CONCLUSIONS: There was considerable variation in the number
      of outliers identified using different detection approaches. Quality programs
      seem to be utilizing outlier identification methods contrary to what might be
      expected, thus they should justify their methodology based on the intent of the
      program (i.e., quality improvement vs. reimbursement). Surgeons and hospitals
      should be aware of variability in methods used to assess their performance as
      these outlier designations will likely have referral and reimbursement
      consequences.

PMID- 20824380
TI  - Eating behavior in rats subjected to vagotomy, sleeve gastrectomy, and duodenal
      switch.
AB  - BACKGROUND/AIM: Food intake, eating behavior, and metabolic parameters in rats
      that underwent bilateral truncal vagotomy, sleeve gastrectomy, and duodenal
      switch procedures were examined. METHODS: Rats were subjected to bilateral
      truncal vagotomy plus pyloroplasty (VTPP), pyloroplasty (PP), laparotomy, sleeve
      gastrectomy (SG), or duodenal switch (DS; with and without SG). RESULTS: VTPP,
      but neither PP nor laparotomy, reduced body weight (BW; 10%) transiently (1 week
      postoperatively). SG reduced BW (10%) for 6 weeks, while DS alone or SG followed
      by DS led to a continuous BW loss from 15% at 1 week to 50% at 8 weeks
      postoperatively. Food intake was higher and the satiety ratio was lower during
      the night than the day for all groups of surgeries. Neither VTPP nor SG had
      measurable effect on food intake, eating behavior and metabolic parameters. DS
      reduced daily food intake by more than 50%, which was associated with
      hypercholecystokinin(CCK)emia, reduced meal size and increased satiety ratio, and
      increased fecal energy content (measured at 8 weeks). CONCLUSIONS: Weight loss
      after VTPP, SG, or DS differed in terms of degree, duration, and underlying
      mechanisms. DS without SG was most effective in the long-term, probably due to
      hyperCCKemia-induced reduction in food intake and long-limb intestinal bypass
      induced malabsorption.

PMID- 20824381
TI  - Radiation dose from computed tomography in patients with necrotizing
      pancreatitis: how much is too much?
AB  - OBJECTIVES: Low-dose ionizing radiation from medical imaging has been indirectly
      linked with subsequent cancer. Computed tomography (CT) is the gold standard for
      defining pancreatic necrosis. The primary goal was to identify the frequency and
      effective radiation dose of CT imaging for patients with necrotizing
      pancreatitis. METHODS: All patients with necrotizing pancreatitis (2003-2007)
      were retrospectively analyzed for CT-related radiation exposure. RESULTS:
      Necrosis was identified in 18% (238/1290) of patients with acute pancreatitis
      (mean age = 53 years; hospital/ICU length of stay = 23/7 days; mortality = 9%). A
      median of five CTs/patient [interquartile range (IQR) = 4] were performed during
      a median 2.6-month interval. The average effective dose was 40 mSv per patient
      (equivalent to 2,000 chest X-rays; 13.2 years of background radiation; one out of
      250 increased risk of fatal cancer). The actual effective dose was 63 mSv
      considering various scanner technologies. CTs were infrequently (20%) followed by
      direct intervention (199 interventional radiology, 118 operative, 12 endoscopic)
      (median = 1; IQR = 2). Magnetic resonance imaging did not have a CT-sparing
      effect. Mean direct hospital costs increased linearly with CT number (R = 0.7).
      CONCLUSIONS: The effective radiation dose received by patients with necrotizing
      pancreatitis is significant. Management changes infrequently follow CT imaging.
      The ubiquitous use of CT in necrotizing pancreatitis raises substantial public
      health concerns and mandates a careful reassessment of its utility.

PMID- 20824382
TI  - Laparoscopic distal pancreatectomy with or without splenectomy: how I do it.
AB  - OBJECTIVES: Although the technique of distal pancreatectomy with or without en
      bloc splenectomy has been well described, the execution of this procedure may be
      technically challenging when performed laparoscopically. In this technical
      report, we aimed to describe the technique of laparoscopic distal pancreatectomy
      with or without splenic preservation. DISCUSSION: Laparoscopic distal
      pancreatectomy with or without splenectomy is a safe and effective surgical
      approach for the correction of various conditions. It has been proven to be a
      feasible solution for the treatment of benign inflammatory conditions as well as
      neoplasms. Splenic preservation requires careful and meticulous dissection, but
      may be done safely.

PMID- 20824383
TI  - Neuroendocrine tumors of Meckel's diverticulum: lessons from a single institution
      study of eight cases.
AB  - INTRODUCTION: Endocrine tumors of Meckel's diverticulum are rare. Their clinical
      and pathological characteristics are not well known, making it difficult to
      assess the best strategy for therapeutic management. MATERIALS AND METHODS: Eight
      cases of endocrine tumors of Meckel's diverticulum, submitted to surgical
      resection in our institution between 1977 and 2009, were studied. Clinical charts
      were reviewed; classification, grading, and staging were performed according to
      recent international recommendations. Five cases, including two associated with
      the carcinoid syndrome, were revealed by mesenteric mass or liver metastases;
      three cases were diagnosed incidentally at laparotomy or laparoscopy. RESULTS:
      All cases presented as typical well-differentiated midgut endocrine tumors. Five
      cases were associated with mesenteric lymph node metastases; three presented with
      liver metastases. Seven cases were classified as well-differentiated endocrine
      carcinomas, one as well-differentiated endocrine tumor of benign behavior.
      DISCUSSION: All tumors >1 cm, but one, had regional or distant disease. All
      patients had complete surgical resection of the primary. One patient deceased
      after 25 months; the others were alive after 12-101 months. CONCLUSION: In
      conclusion, endocrine tumors of Meckel's diverticulum are rarely symptomatic and
      often diagnosed at an advanced stage. All tumors measuring more than 1 cm in
      diameter must be resected according to oncological principles.

PMID- 20824384
TI  - The effect of surgical volume and the provision of residency and fellowship
      training on complications of major hepatic resection.
AB  - BACKGROUND: Positive volume-outcomes relationships have been demonstrated for
      hepatic resection using arbitrary criteria to define high-volume centers. The
      safety of training programs has not been evaluated. The association of surgical
      volume, as a continuous variable and the influence of a surgical residency and a
      fellowship program on outcomes after major hepatectomy were determined. METHODS:
      The Nationwide Inpatient Sample (NIS) was queried from 1998 to 2006.
      Quantification of patients' comorbidities was made using the Charlson index, and
      mortality, and complication rates were determined. Institutions' annual case
      volumes were correlated with risk-adjusted outcomes over time, as well as
      presence or absence of residency or fellowship training program using logistic
      regression modeling. RESULTS: A total of 5,298 major hepatectomies were recorded,
      representing a weighted nationwide total of 26,396 cases. In-hospital unadjusted
      mortality for the study period was 6%. Adjusting for comorbidities, greater major
      hepatectomy volume was associated with improvements in the incidence of most
      measured complications, with plateauing of mortality of between 2% and 3% at
      approximately 50 cases per year. The mortality rate increased once greater than
      approximately 70 cases were performed per annum. Hospitals supporting a surgical
      residency program had lower overall morbidity and mortality. A fellowship program
      however was not associated with overall lower morbidity and mortality and
      appeared to result in a higher rate of certain complications. CONCLUSIONS:
      Greater annual major hepatectomy volume improves outcomes with reduced mortality
      up to a certain point. The presence of surgical residency program but not a
      fellowship program is associated with reduced predicted morbidity and mortality.

PMID- 20824385
TI  - Laparoscopic repair of large hiatal hernia without prosthetic reinforcement: late
      results and relevance of anterior gastropexy.
AB  - BACKGROUND: Laparoscopic treatment of large hiatal hernias seems to be associated
      with a high recurrence rate that some authors suggest to bring down by performing
      prosthetic closure of the hiatus. However, prosthetic repair remains
      controversial owing to severe and still underestimated complications. The aims of
      this study were to assess the long-term functional and objective results of
      laparoscopic treatment without prosthetic patch, and to identify the risk factors
      of recurrence. METHODS: From November 1992 to March 2009, 89 patients underwent
      laparoscopic treatment of a large hiatal hernia without prosthetic patch,
      involving excision of the hernial sac, cruroplasty, fundoplication, and often
      anterior gastropexy. The postoperative assessment consisted of a barium
      esophagram on day 2, an office visit at 2 months with a 24-h pH study, an
      esophageal manometry, and then a long-term prospective yearly follow-up with a
      barium esophagram at 2 years. RESULTS: Out of the 89 laparoscopic procedures,
      four required a conversion (4.4%). Seventy-seven patients underwent a Boerema's
      anterior gastropexy (86.5%). The morbidity rate was 7.8%, and the mortality rate
      was nil. Eleven patients (12.3%) were lost to follow-up. We had 91.5% of very
      good early functional results and 75.3% of good results after a mean follow-up of
      57.5 months. Fourteen recurrences of hiatal hernias (15.7%) were identified, four
      of which (28.6%) occurred early after surgery. Three factors seemed significantly
      associated with recurrence: the absence of anterior gastropexy (p = 0.0028), the
      group of younger patients (p = 0.03), and a history of abdominal surgery (p =
      0.01). CONCLUSION: Large hiatal hernias can be treated by laparoscopy without
      prosthetic patch with a satisfying long-term result. Performing anterior
      gastropexy seems to significantly reduce the recurrences.

PMID- 20824386
TI  - The impact of scoliosis among patients with giant paraesophageal hernia.
AB  - BACKGROUND: Kyphoscoliosis is seen in approximately 1.4-15% of the octogenarian
      population of the US. We hypothesized that patients with kyphoscoliosis are
      affected with a reduced intra-abdominal volume and progressive laxity of the
      diaphragmatic hiatal sling musculature leading to an increased risk of hiatal
      hernia formation and progression over time. METHODS: We retrospectively reviewed
      the clinical history and roentgenographic data of 320 paraesophageal hernia
      patients from 2003 to 2007. The prevalence of kyphoscoliosis among this patient
      cohort and the outcomes of surgical management were compared to paraesophageal
      hernia patients without kyphoscoliosis. RESULTS: Ninety-three of the 320 patients
      (29.1%) were found to have significant K/S (mean age 74; 83% female).
      Laparoscopic repair of paraesophageal hernia with fundoplication was performed in
      91% of these patients. There was one death (1.1%; aspiration pneumonia) and 17.2%
      major postoperative morbidity. Mean length of hospital stay was 8 days (median =
      4; range 2-71). Prolonged stays were related mainly to marginal pulmonary status.
      Kyphoscoliosis was associated with increased peri-operative pulmonary morbidity
      (16.1%) compared to patients without kyphoscoliosis (7.0%, p = 0.02). CONCLUSION:
      Kyphoscoliosis may contribute to the development and progression of
      paraesophageal hernias. Surgeons approaching paraesophageal hernia repair should
      be aware of the increased pulmonary morbidity and the postoperative care required
      in managing these patients.

PMID- 20824387
TI  - A protective technique for retraction of the liver during laparoscopic
      gastrectomy for gastric adenocarcinoma: using a Penrose drain.
AB  - BACKGROUND: Retraction of the liver is necessary to ensure an adequate working
      space in laparoscopic surgery, but the retraction force applied may cause
      transient liver dysfunction. We have introduced the technique using a Penrose
      drain to suspend the liver with the performance of laparoscopic gastrectomy for
      gastric adenocarcinoma. METHODS: 111 patients with gastric adenocarcinoma
      underwent laparoscopic gastrectomy using either a Penrose drain (n = 47) or a
      Nathanson's retractor (n = 64) for displacement of the liver. Serum levels of
      alanine aminotransferase (ALT), aspartate aminotransferase (AST), total
      bilirubin, alkaline phosphatase (ALP) and albumin were compared among the groups
      at baseline, immediately after operation, and on postoperative days (POD) 1, 2,
      3, 5, and 7. RESULTS: The levels of ALT on POD 2, 3, and 5 were significant
      higher in the Nathanson's retractor group than in the Penrose drain group. Levels
      of AST on POD 2 and 3 were also higher in the Nathanson's retractor group than in
      the Penrose drain group. There was no significant difference in total bilirubin,
      ALP, and serum albumin levels between groups. CONCLUSIONS: The use of the Penrose
      drain for retraction of the liver appears to attenuate postoperative liver
      dysfunction during laparoscopic gastrectomy for gastric adenocarcinoma.

PMID- 20824388
TI  - Oxidative stress and apoptosis in relation to exposure to magnetic field.
AB  - We investigated the effect of extremely low-frequency electromagnetic field (ELF
      EMF) with pulse trains exposure on lipid peroxidation, and, hence, oxidative
      stress in the rat liver tissue. The parameters that we measured were the levels
      of plasma alanine aminotransferase, aspartate aminotransferase, and alkaline
      phosphatase as well as plasma albumin, bilirubin, and total protein levels in 30
      adult male Wistar rats exposed to ELF. We also determined the percentage of
      apoptotic and necrotic cells of the kidney extracts from the animals by flow
      cytometry method. Apoptotic cell death was further characterized by monitoring
      DNA degradation using gel electrophoresis. The results showed an increase in the
      levels of oxidative stress indicators, and the flow cytometric data suggested a
      possible relationship between the exposure to magnetic field and the cell death.
      We showed significantly lower necrotic cell percentages in experimental animals
      compared to either unexposed or sham control groups. However, DNA ladder analyses
      did not differentiate between the groups. Our results were discussed in relation
      to the response of biological systems to EMF.

PMID- 20824391
TI  - Primary cutaneous small-cell carcinoma: a case report.
AB  - Most commonly arising in the gastrointestinal and genitourinary tracts,
      extrapulmonary small-cell carcinoma is quite rare. Although its prognosis is very
      poor, complete remission or even cure can be achieved by combination of different
      treatment modalities. We report here a 32-year-old woman with a cutaneous gluteal
      mass diagnosed as small-cell carcinoma of the skin. Combination chemotherapy
      containing cisplatin and etoposide was started. Radiotherapy was administered
      after two courses of chemotherapy. Following radiotherapy, additional 4 courses
      of chemotherapy were given. She has been in remission for three years with no
      evidence of tumor recurrence.

PMID- 20824390
TI  - ttime: an R package for translating the timing of brain development across
      mammalian species.
AB  - Understanding relationships between the sequence and timing of brain
      developmental events across a given set of mammalian species can provide
      information about both neural development and evolution. Yet neurodevelopmental
      event timing data available from the published literature are incomplete,
      particularly for humans. Experimental documentation of unknown event timings
      requires considerable effort that can be expensive, time consuming, and for
      humans, often impossible. Application of suitable statistical models for
      translating neurodevelopmental event timings across mammalian species is
      essential. The present study implements an established statistical model and
      related functions as an open-source R package (ttime, translating time). The
      model incorporated into ttime allows predictions of unknown neurodevelopmental
      timings and explorations of phylogenetic relationships. The open-source package
      will enable transparency and reproducibility while minimizing redundancy.
      Sustainability and widespread dissemination will be guaranteed by the active CRAN
      (Comprehensive R Archive Network) community. The package updates the web-service
      (Clancy et al. 2007b) www.translatingtime.net by permitting predictions based on
      curated event timing databases which may include species not yet incorporated in
      the current model. The R package can be integrated into complex workflows that
      use the event predictions in their analyses. The package ttime is publicly
      available and can be downloaded from http://cran.r
      project.org/web/packages/ttime/index.html .

PMID- 20824392
TI  - Prevalence of pediatrics metabolic syndrome (PMS) amongst children in the age
      group of 6-18 years belonging to high income group residing in national capital
      territory (NCT) of Delhi.

PMID- 20824394
TI  - The neuroanatomic correlates of semantic memory deficits in patients with Gulf
      War illnesses: a pilot study.
AB  - We used functional magnetic resonance imaging (fMRI) to study semantic memory
      processing in 38 Gulf War veterans in 3 affected groups (Syndromes 1, 2, and 3)
      and normal-deployed controls. Subjects were given the Semantic Object Retrieval
      Test (SORT), which requires participants to decide whether two features combine
      and result in the retrieval of a specific object (e.g., "desert" and "humps" ->
      "camel"). Differences between groups were calculated using a repeated measures
      analysis of variance (ANOVA). Then, regions of interest were constructed and
      correlations assessed between the percent signal change (PSC) within these
      regions, followed by correlations between behavioral measures and PSC. We found
      affected groups performed less well on the SORT than the controls did, and
      behavioral differences were correlated to PSC within the caudate and thalamus.
      The combination of performance deficits and functional neuroimaging differences
      between affected Gulf War veterans and deployed normal controls begins to
      establish a neurobiological basis for their word-finding deficits.

PMID- 20824393
TI  - Management of status asthmaticus in children.
AB  - Asthma is a common chronic inflammatory disorder of the airways characterized by
      recurrent wheezing, breathlessness, and coughing. Acute exacerbations of asthma
      can be life-threatening; annual worldwide estimated mortality is 250,000 and most
      of these deaths are preventable. While most of the acute exacerbations can be
      managed successfully in the emergency room, few children have severe
      exacerbations requiring intensive care. Mainstay of treatment for status
      asthmaticus are inhaled beta2 agonist and anticholinergic agents, oxygen along
      with corticosteroids. Children who do not respond well to initial treatment
      require parenteral beta2 agonist and magnesium. Rarely, sick children need
      parenteral aminophylline infusion and mechanical ventilation. Guidelines for
      diagnosis, treatment, ventilator management and supportive care for status
      asthmaticus in children are discussed in the protocol.

PMID- 20824395
TI  - Decreased brain FDG uptake in patients with extensive non-Hodgkin's lymphoma
      lesions.
AB  - OBJECTIVE: Faint brain [(18)F]fluoro-2-deoxyglucose (FDG) uptake has sporadically
      been reported in patients with FDG-avid large or diffusely extended tumors. The
      purpose of this study was to investigate whether there is a correlation between
      massive tumor uptake and decreased brain uptake on FDG positron emission
      tomography/computed tomography (PET/CT). METHODS: Sixty-five patients with
      histologically confirmed non-Hodgkin's lymphoma who underwent FDG-PET/CT were
      enrolled. Thirty control subjects were also included to evaluate normal brain FDG
      uptake. PET/CT examinations were retrospectively reviewed. The volumetric regions
      of interest were placed over lesions by referring to CT and PET/CT fusion images
      to measure mean standardized uptake value (SUVavg). The products of SUVavg and
      tumor volume were calculated as total glycolytic volume (TGV). The maximum SUV
      (SUVmax) and SUVavg were measured in the cerebrum and cerebellum. The values of
      TGV and brain FDG uptake were plotted and analyzed with a linear regression
      method. RESULTS: In the lymphoma patients, there were statistically significant
      negative correlations between TGV and brain SUVs. CONCLUSION: Demonstrating a
      significant negative correlation between TGV and brain uptake validated the
      phenomenon of decreased brain FDG uptake. Diversion of FDG from the brain to the
      lymphoma tissue may occur during the FDG accumulation process. Recognition of
      this phenomenon prevents unnecessary further neurological examinations in such
      cases.

PMID- 20824396
TI  - A simple test to determine the quality of your clinical PET images.
AB  - OBJECTIVE: The objective of the study was to present a simple method for
      comparing clinical PET images to a set of increasing quality images. Those
      different quality images were obtained by varying the activity concentration and
      the acquisition time. METHODS: Images of a Jaszczak phantom were acquired with
      scan times that were calculated with a spreadsheet application for a personal
      computer to obtain 500, 1000, 2000, 5000, 7000 and 9000 counts/4 mm(3) voxel.
      During a 10-h period, each scan was repeated with longer acquisition times to
      obtain the same number of counts in the reconstructed images, but with lower
      count rate. On the second day, the study was repeated, putting the phantom in a
      water bath to simulate larger patients. RESULTS: The quality of the images
      obtained with the phantom in water was worse than without, as expected. Phantom
      data demonstrated clearly the effect of higher counts on image quality. Good
      quality images were obtained with counts above 5000 counts/voxel. Patient data
      can be situated to the phantom image set by comparing the counts per voxel and
      the activity concentration. The counts per voxel in all the regions of interest
      on patient data, with the exception of the brain, were at sub-optimal level
      leading to decreased image quality. It is clear that better image quality can be
      achieved mainly by incrementing the scan time. Our PET system, however, allows
      doubling our standard injected activity to obtain more image counts without
      significant contrast loss. CONCLUSION: This simple test can be performed at any
      PET center to situate the quality of routine clinical PET images in comparison to
      the optimal possible for that system.

PMID- 20824397
TI  - Ratio of standardized uptake value on PET helps predict response and outcome
      after chemotherapy in advanced non-small cell lung cancer.
AB  - BACKGROUND: The maximum standardized uptake value (SUV(max)) on (18)F
      fluorodeoxyglucose-positron emission tomography ((18)F-FDG PET) within the
      primary tumor may predict outcome in patients with surgically resected non-small
      cell lung cancer (NSCLC). However, it remains uncertain whether the SUV(max) of
      the primary tumor predicts outcome after chemotherapy in advanced NSCLC. Thus, we
      evaluated the ratio of SUV(max) of the metastatic tumor to the primary tumor (M/P
      ratio) to determine whether it could be a useful marker in predicting response
      and outcome after chemotherapy in advanced NSCLC. METHODS: Chemo-naive patients
      with advanced NSCLC who had locoregional lymph nodes and/or distant metastases
      other than brain, were eligible for inclusion in this study. Response and
      survival were analyzed according to the SUV(max) of primary tumor, the ratio of
      the SUV(max) of the tumor to the mean SUV of the mediastinum (T/M ratio) and M/P
      ratio. RESULTS: One hundred and four consecutive patients were included in the
      retrospective study. Patients with high M/P ratio exhibited significantly lower
      response rates. The value of SUV(max) and T/M ratio were not associated with the
      response to initial chemotherapy. In the univariate analysis, T/M ratio and
      SUV(max) were significantly associated with poor outcome. However, the outcome of
      non-adenocarcinoma was unaffected by T/M ratio and SUV(max). Multivariate
      analysis confirmed that high M/P ratio was a significant independent factor
      predicting a poor outcome. CONCLUSION: High M/P ratio was associated with a poor
      response to initial chemotherapy and was a significant independent factor in
      predicting poor outcome in advanced NSCLC patients with metastatic tumors other
      than in brain.

PMID- 20824398
TI  - Iodine-123-metaiodobenzylguanidine imaging can predict future cardiac events in
      heart failure patients with preserved ejection fraction.
AB  - OBJECTIVE: Iodine-123-metaiodobenzylguanidine ((123)I-MIBG) has been used to
      assess the function of the cardiac sympathetic nervous system in patients with
      chronic heart failure (HF). The usefulness of (123)I-MIBG imaging for evaluating
      patients with heart failure with preserved ejection fraction (HFPEF) has not been
      established. METHODS: We performed (123)I-MIBG scintigraphy and echocardiography
      and measured the plasma brain natriuretic peptide (BNP) levels of 117 consecutive
      HF patients (64 men, mean age 66 +/- 14 years) with a left ventricular ejection
      fraction (LVEF) of >=50% who were admitted to our hospital. Patients were divided
      into 2 groups according to the New York Heart Association (NYHA) functional
      class. RESULTS: The (123)I-MIBG delayed heart-to-mediastinum (H/M) ratio was
      significantly lower, and the washout rate (WR) was higher in patients with HFPEF
      with advanced NYHA functional class (NYHA functional class I and II vs. III: 1.90
      +/- 0.34 vs. 1.49 +/- 0.32, p < 0.0001; 25.9 +/- 13.4 vs. 46.9 +/- 16.3%, p <
      0.0001, respectively). On the other hand, the (123)I-MIBG WR was not correlated
      with LVEF and had a weak correlation with plasma BNP levels (R = 0.207, p =
      0.0346). Moreover, patients with a high (123)I-MIBG WR showed a poor clinical
      outcome (p = 0.0033). CONCLUSIONS: (123)I-MIBG imaging provides independent
      prognostic information in patients with HFPEF.

PMID- 20824399
TI  - Dasatinib followed by second allogeneic hematopoietic stem cell transplantation
      for relapse of Philadelphia chromosome-positive acute lymphoblastic leukemia
      after the first transplantation.
AB  - Although allogeneic hematopoietic stem cell transplantation (HSCT) is an
      established treatment for Philadelphia chromosome-positive acute lymphoblastic
      leukemia (ALL), the prognosis of patients who relapse after allogeneic HSCT has
      been extremely poor. Dasatinib, a second-generation tyrosine kinase inhibitor, is
      a promising agent for the treatment of Ph-ALL. We report on a Ph-ALL patient who
      relapsed early after the first allogeneic HSCT, but achieved complete molecular
      remission with dasatinib alone. She remains in molecular remission 12 months
      after the second allogeneic HSCT. Dasatinib was generally well tolerated, but she
      developed myalgia, nausea and positive cytomegalovirus antigenemia. In addition,
      sudden-onset bloody diarrhea was observed 10 days after the second HSCT, which
      was possibly associated with the use of dasatinib in addition to the effect of
      the conditioning regimen and graft-versus-host disease. In conclusion, dasatinib
      is an effective agent for Ph-ALL with a poor prognosis, but may be associated
      with specific adverse events including opportunistic infection and
      gastrointestinal bleeding.

PMID- 20824400
TI  - Hemorrhagic colonic ulcers caused by dasatinib for chronic myelogenous leukemia.

PMID- 20824401
TI  - A phase I study of bortezomib in combination with doxorubicin and intermediate
      dose dexamethasone (iPAD therapy) for relapsed or refractory multiple myeloma.
AB  - Bortezomib and doxorubicin have synergistic activity against myeloma cells in
      vitro. We underwent a dose finding study of bortezomib in combination with a
      fixed dose of doxorubicin and intermediate-dose dexamethasone (iPAD therapy) in
      patients with relapsed or refractory myeloma. Bortezomib was administered on days
      1, 4, 8 and 11 at a dose of 1.0 and 1.3 mg/m2 in cohorts 1 and 2, respectively.
      Doxorubicin 9 mg/m2 was given by rapid intravenous infusion on days 1-4, and
      dexamethasone 20 mg on days 1-2, 4-5, 8-9 and 11-12. Treatment was repeated at a
      3-week interval and the dose-limiting toxicity (DLT), defined as grade 4
      hematological toxicity lasting more than 5 days and/or grade 3 or higher non
      hematological toxicity, was evaluated. In cohort 1, 2 of 6 patients developed
      DLTs including grade 4 hyponatremia and grade 3 infection with appropriate
      neutrophil counts. No DLT was observed in the remaining 4 patients, indicating
      this dose was tolerable. In cohort 2, 3 of 5 patients developed DLTs including
      grade 4 thrombocytopenia lasting more than 5 days, grade 3 hepatic transaminase
      elevation and grade 3 ileus, indicating this dose was intolerable. It is
      concluded that bortezomib at the dose of 1.0 mg/m2 is recommended in combination
      with doxorubicin and intermediate-dose dexamethasone.

PMID- 20824402
TI  - The classic: The bonding of prostheses to bone by cement. 1964.

PMID- 20824403
TI  - 50 years ago in CORR: Acrylic hip endoprostheses. Dana M. Street MD CORR
      1955;6:72-85.

PMID- 20824404
TI  - Variability of expert opinion in treatment of early-onset scoliosis.
AB  - BACKGROUND: In contrast with treatment recommendations for adolescent idiopathic
      scoliosis, there are no clear algorithms for treating patients with early-onset
      scoliosis. There has been rapid expansion of treatment options for children with
      early-onset scoliosis, including casting, growth rods, the vertical expandable
      prosthetic titanium rib, and anterior vertebral stapling. QUESTIONS/PURPOSES:
      Given the range of treatment options, we assessed variability in decision making
      regarding treatment of patients with early-onset scoliosis. METHODS: We presented
      12 clinical and radiographic vignettes about patients with early-onset scoliosis
      to 13 experienced spine surgeons who are members of the Chest Wall and Spine
      Deformity Study Group. The reviewers were asked to choose type of treatment, type
      of construct, construct location, and whether a thoracotomy should be performed.
      RESULTS: All 13 surgeons agreed regarding the need for surgery in eight of the 12
      cases. When the reviewers chose surgery, 76% (40%-100%) selected the vertical
      expandable prosthetic titanium rib; of those selecting that approach, 61% (0%
      100%) coincided on using it bilaterally. Agreement was 20% (0%-60%) for growing
      rods and 4% (0%-25%) for fusions. Among all cases, agreement regarding whether
      instrumentation should extend to the pelvis was 71% (50%-100%). In all but two
      cases, at least 85% of surgeons recommended against a thoracotomy. CONCLUSIONS:
      Although most surgeons agreed about the indication for surgery, we found wide
      variability in choice of construct type, number of constructs, and level of
      instrumentation.

PMID- 20824405
TI  - Quality of life following proximal femoral replacement using a modular system in
      revision THA.
AB  - BACKGROUND: Proximal femoral replacement using a segmental modular system is one
      option for revision THA in the presence of severe bone loss or periprosthetic
      fracture. While many papers report function in these patients, they do not
      describe the quality of life. QUESTIONS/PURPOSES: We evaluated the quality of
      life in patients undergoing proximal femoral replacement using a segmental
      modular system for severe bone loss. PATIENTS AND METHODS: We retrospectively
      reviewed 63 patients undergoing complex revision THA using a modular replacement
      system for nonneoplastic conditions between April 1996 and June 2006. Average age
      was 73 years (range, 23-94 years). Twenty-one patients were lost to followup and
      six patients died before 2-year minimum followup. The remaining 36 patients were
      followed for an average of 3.2 years (range, 2-10 years). Study patients were
      matched by age-decade to a control group of patients undergoing conventional
      revision THA. At baseline, both groups were comparable with respect to age,
      comorbidities, and quality-of-life scores. RESULTS: At last followup, the modular
      system group showed improvement in WOMAC function, WOMAC pain, Oxford score, and
      the SF-12 mental component. Compared to the control group, the modular system
      group scored lower on WOMAC function and Oxford scores, but there were no
      differences in any other scores. CONCLUSIONS: In patients with severely
      compromised bone stock, a segmental modular replacement system can improve the
      quality of life. Special attention should be given to the stability of the hip
      intraoperatively and a constrained acetabular liner should be used when the risk
      of postoperative dislocation is high. LEVEL OF EVIDENCE: Level III, therapeutic
      study. See the Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 20824406
TI  - CT angiography for anterior lumbar spine access: high radiation exposure and low
      clinical relevance.
AB  - BACKGROUND: Some spine surgeons perform CT angiography for detailed planning of
      anterior access to the lumbar spine. However, the value of this imaging method
      and its influence on surgeons' decisions are unclear. QUESTIONS/PURPOSES: We
      determined (1) the dose of radiation used in preoperative CT angiography and (2)
      whether CT angiography affects planning of anterior lumbar spine surgeries.
      PATIENTS AND METHODS: We assessed preoperative CT angiograms of 28 patients
      undergoing anterior spine surgery. The level of aortic bifurcation, iliac vein
      confluence, course of the ascending lumbar vein, central sacral vessels, and any
      vascular variation were mapped. We determined the effective dose of radiation and
      recorded whether the preoperative CT angiography influenced surgical planning.
      RESULTS: We observed variations in the location of the aortic bifurcation and the
      iliac vein confluence. In 32% of patients, there were accessory renal arteries
      originating from the aorta; 7% had a rudimentary persistent left-sided caval
      vein. The findings did not change the plan for surgery in any patient. We
      detected high organ radiation dosages (mSv) for the stomach (63 mSv), liver (58
      mSv), urinary bladder (47 mSv), and colon (46 mSv); other high exposure dosages
      involved the lungs, bone marrow, ovaries, and uterus. CONCLUSIONS: About one in
      1919 men and one in 2971 women undergoing CT angiography therefore are expected
      to have colon cancer develop, and one in 2781 men and one in 2856 women are
      expected to have cancer of the urinary bladder develop. CT angiography is of low
      value for preoperative planning for anterior access to the lumbar spine and
      should be avoided to prevent radiation-induced damage. LEVEL OF EVIDENCE: Level
      II, diagnostic study.

PMID- 20824407
TI  - The incidence of acetabular osteolysis in young patients with conventional versus
      highly crosslinked polyethylene.
AB  - BACKGROUND: Osteolysis is a major mode of hip implant failure. Previous
      literature has focused on the amount of polyethylene wear comparing highly
      crosslinked polyethylene (HXPLE) with conventional liners but has not clarified
      the relative incidence of osteolysis with these two liners. QUESTIONS/PURPOSES:
      We determined (1) the incidence of osteolysis in HXLPE versus conventional
      polyethylene (CPE), (2) the ability to detect and evaluate the size of lytic
      lesions using radiographs compared with CT scans, (3) head penetration in hips
      without and with lysis, and (4) determined whether acetabular position, head
      size, and UCLA activity score contributed to lysis. METHODS: We compared head
      penetration and osteolysis on plain radiographs and presence and volume of
      osteolysis on CT scans in 48 patients with HXLPE (mean, 46.5 years) and 50
      patients with CPE (mean, 43.2 years). The minimum followup was 5 years (average,
      7.2 years; range, 5.1-10.9 years), RESULTS: Osteolysis was apparent on CT in a
      larger number of patients with CPE liners than HXLPE liners: 12 of 50 (24%)
      versus one of 48 (2%), respectively. We found no correlation between head
      penetration and volume of osteolytic lesions. Head penetration was greater in
      patients with osteolysis. Smaller head sizes were associated with greater wear
      and those with osteolysis had smaller head sizes; however, there was no
      difference in acetabular component position or UCLA activity in those with lysis
      compared with those without. CONCLUSIONS: HXLPE diminished the incidence of
      osteolysis, but the lack of correlation between penetration and volume of
      osteolysis suggests other factors other than wear contribute to the development
      of osteolysis. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines
      for Authors for a complete description of levels of evidence.

PMID- 20824408
TI  - Hematologic genetic testing in high-risk patients before knee arthroplasty: a
      pilot study.
AB  - BACKGROUND: Patients with a personal or familial history of thromboembolism are
      considered at higher risk for thromboembolic disease after knee arthroplasty.
      While it remains unclear why some patients develop deep vein thrombosis (DVT) or
      pulmonary embolism (PE) despite similar operative procedures and the same
      prophylactic regimen, we presume one explanation would be genetic predisposition.
      QUESTIONS/PURPOSES: We determined the frequency of 12 factors including
      antithrombin III activity, prothrombin gene mutations, and the presence of
      phospholipid antibodies in a high-risk patient cohort and compared those findings
      with the known prevalence in the population at large. PATIENTS AND METHODS:
      Patients identified preoperatively as having a personal or familial history of
      DVT and/or PE were referred for hemostatic serum and genetic tests, including %
      antithrombin III activity (ATIII), protein C and protein S activities, APC
      resistance, Factor V gene (Leiden) mutations, prothrombin gene mutations, lupus
      anticoagulant antibody presence, cardiolipin antibody presence, phosphatidyl
      antibody presence, beta2-glycoprotein antibody presence, and serum homocysteine
      and lipoprotein(a) levels The frequencies of varying abnormalities were
      identified and compared to the prevalence reported in the literature. RESULTS:
      Forty-three of 1944 patients undergoing knee arthroplasty had a history of DVT or
      PE. Sixteen of 43 (37%) patients had an abnormality and eight of these (19%) had
      two or more abnormalities. The frequency of nine of the 12 tests appeared to be
      greater in this cohort than in the population at large. CONCLUSIONS: Patients
      with a personal or familial history of DVT or PE appear to have a high frequency
      of hereditary prothrombotic abnormalities. Preoperative evaluation by a
      hematologist may be warranted in patients with a personal or familial history of
      DVT or PE as the postoperative anticoagulation protocols may be altered and
      identification of these abnormalities may affect a patient's risk for other
      disease states. LEVEL OF EVIDENCE: Level IV, diagnostic study. See Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 20824409
TI  - Hyperbaric oxygen effect on MMP-9 after a vascular insult.
AB  - Matrix metalloproteinease-9 (MMP-9) is involved in a host of processes. Many of
      its processes are physiologically beneficial as well as detrimental. The over
      expression of this enzyme has been implicated as a contributory factor to some of
      the sequalae associated with cerebral ischemia, cell death, non-healing wounds,
      traumatic brain injury, aneurysms, and plaque instability in atherosclerosis.
      Several studies have examined the effect of hyperbaric oxygen (HBO) on MMP-9
      expression. Because this proteinase is involved in both chronic and acute
      pathology, we wanted to investigate an acute expression model and see if, and how
      quickly, its expression would respond to HBO therapy. Our patient was scheduled
      to have elective surgery with an overnight stay followed by a series of HBO
      exposures. The patient served as her own control. An MMP-9 and urine pH was
      obtained prior to surgery to establish a baseline. On days 1, 3, and 4 post-op,
      samples were obtained before and after hyperbaric exposure. The patient was
      exposed to 100% O2 at 2.5 ATA for 60 min during each treatment for 5 days. The
      patient's MMP-9 values were dramatically elevated after surgery as compared to
      the baseline readings. The percentage increase from baseline was 400%. Our
      patient showed a significant reduction in MMP-9 expression after each hyperbaric
      exposure with the greatest decrease seen on post-op day 1 and subsequent
      exposures showing slightly less expression. Reduction in MMP-9 expression ranged
      from 46% on day 1 to 30% on post-op day 4. This case study suggests that if done
      relatively soon after a vascular or tissue insult, HBO can reduce MMP-9
      expression. Chronic vascular pathologies, such as atherosclerotic plaque and
      aneurysms where over-expression of MMP-9 may result in acute coronary syndrome
      (ACS) or cerebral vascular accidents (CVAs), may be mitigated by a series of HBO
      treatments that reduce MMP-9 expression. Causality and/or contributory effects of
      MMP-9 expression in both pathologic and physiologic processes needs to be further
      elucidated. The understanding of how HBO therapy modulates these may provide an
      additional insight into mechanisms and future potential therapies for pathologic
      conditions such as those described above.

PMID- 20824410
TI  - [Analysis of costs and profits of ambulatory care of Marfan patients after
      initiation of a novel German legal directive (116 b SGB V)].
AB  - BACKGROUND: The Marfan syndrome is a typical rare disease with multiorgan
      involvement and the need for specialized interdisciplinary medical care. A novel
      German legal directive according to section sign 116 b of the Social Statutes
      Book V (116 b SGB V) improves options for reimbursement and thus encourages
      specialized hospitals to provide ambulatory care for rare diseases such as Marfan
      syndrome. The authors provide the first economic analysis of section sign 116 b
      in a German Marfan center. METHODS: The costs were assessed in 184 cases with
      Marfan syndrome receiving medical care in the Hamburg Marfan Clinic. The authors
      assessed the financial profit both according to payments received from invoices
      established according to the 116 b directive [reimbursement (116b)] and from
      calculations according to section sign 117 SGB V [reimbursement (117)]. RESULTS:
      A total of 117 patients traveled to the Marfan clinic (64%) < 50 km, 27 patients
      (15%) between >or= 50 and <or= 100 km, and 40 patients (22%) > 100 km. The total
      costs for ambulatory care were 71,606.28 Euro. The reimbursement (116b) was
      55,549.87 Euro and the reimbursement (117) was 11,776.00 Euro. CONCLUSION: Many
      patients accept long distances of traveling to receive specialized ambulatory
      medical care. However, for optimal patient management specialized centers need to
      cooperate intensively with local health care providers. The novel legal directive
      according to section sign 116 b has significantly improved reimbursement for
      Marfan centers and allows for improving the quality of medical care.

PMID- 20824411
TI  - [Counting reticulocytes: new importance of an old method].
AB  - In clinical practice, the reticulocyte count is the most useful method to
      estimate red cell life span and red cell production. However, experience of
      hematologists as well as surveys have shown that counting of reticulocytes is
      often neglected in the diagnostic work-up of unclassified anemias, and many
      physicians have difficulties in interpreting the results. Formerly, this was
      partly due to the low precision of manual counts. Today, this method is largely
      replaced by flow cytometry, available in almost all larger systems for automated
      blood count analysis, at low costs and sufficient analytic precision.
      Interpretation is supported by calculated parameters such as the Reticulocyte
      Production Index. Here, the authors discuss the limits of the analytic methods
      and the problems of interpretation in the context of the laboratory profile and
      the clinical setting.

PMID- 20824412
TI  - [Systemic mastocytosis--definition of an internal disease].
AB  - Systemic mastocytosis comprises disorders characterized by an accumulation of
      genetically altered mast cells in all organs and tissues due to an increased
      proliferation rate and reduced apoptosis of those pathologic mast cells. Release
      of their mediators can effectively influence organ function and can lead to
      systemic effects without inducing traces in routinely used laboratory parameters
      or imaging methods. In most cases, little invasive investigations allow
      diagnosing the disease and, hence, an appropriate therapy consisting of a basic
      medication with antihistamine and mast cell membrane-stabilizing compounds that
      should be supplemented, if required, by a medication adapted to individual
      symptoms, can be initiated. Because of the probably high prevalence of the
      disorder, systemic mastocytosis should be considered as a differential diagnosis
      in particular in the case of chronic gastrointestinal complaints such as
      abdominal pain/discomfort possibly associated with diarrhea, at an early stage.

PMID- 20824413
TI  - [Colorectal cancer prevention by flavonoids].
AB  - BACKGROUND: Valid, sustained and safe clinical means of colorectal cancer
      prevention are still lacking, but they are urgently needed to lower the incidence
      of colorectal cancer. Dietary factors and phytochemicals such as flavonoids play
      an important role for prevention. METHODS: A selective search of the literature
      using PubMed was performed with the following key words: flavonoids, cancer,
      therapy, colorectal cancer focused on clinical queries. Results of clinical
      studies including the authors' own were compared. RESULTS: In vivo and in vitro
      studies with animals, cell cultures and subcellular components provide ample
      evidence for antimutagenic and anticarcinogenic effects of flavonoids as shown
      for multiple biological and molecular endpoints. Isoflavonoids in vitro have been
      shown to induce proliferation of breast cancer cells. Epidemiologic trials
      (cohort, case-control and cross-sectional studies) yielded inconsistent results
      for flavonoid protection. Systematic reviews and meta-analyses support the
      protective role of tea flavonoids on adenoma incidence. An interventional pilot
      study with sustained flavonoid supplementation was shown to reduce the rate of
      neoplasia in patients with resected colorectal cancer. CONCLUSION: Selected
      flavonoids possess antimutagenic and anticarcinogenic properties and could reduce
      the incidence of colorectal neoplasias as shown in epidemiologic trials.
      Randomized controlled clinical studies with flavonoid intervention are necessary
      to provide evidence for their role in colorectal cancer prevention.

PMID- 20824414
TI  - [Is "evidence-based medicine" followed by "confidence-based medicine"?].
AB  - In an appeal concerning accusations of defamation, the England and Wales Court of
      Appeal Decisions determined that evidence-based statements are to be judged as
      opinions and not statements of fact. Since the authors consider it probable that
      this legal judgment will exert influence on physicians' decisions about the
      provision of health care services, they have compiled the implications of the
      judgment and discuss its consequences. The own analyses and considerations lead
      to the conclusion that confidence-based medicine follows evidence-based medicine.
      This extension is necessary because evidence-based medicine has not been able to
      generate the required trust. Therefore, it will be demanded to underpin the
      existing concept with additional data. These data will be necessary because it is
      no longer sufficient to convince scientists with data which are obtained under
      ideal conditions, but to convince critical members of society with additional
      data which have been obtained under everyday conditions.

PMID- 20824415
TI  - [Primary hyperparathyroidism - current diagnosis and therapy].

PMID- 20824416
TI  - [Digital ulcers in systemic sclerosis--an interdisciplinary challenge].
AB  - Digital ulcers in systemic sclerosis are painful ischemic necrotic lesions of the
      acra. Optimal treatment consists of conventional wound management and medication:
      iloprost infusions promote primary healing of the ulcers, while the dual
      endothelin receptor antagonist bosentan is used for secondary prophylaxis of new
      ulcers. The described case illustrates the essential interdisciplinary
      collaboration for optimal management of these patients.

PMID- 20824417
TI  - [Imaging of retroperitoneal fibrosis].

PMID- 20824421
TI  - [Results of various surgical techniques for proximal humeral fracture].

PMID- 20824422
TI  - [Treatment of carpal fractures. Recommendations of the Hand Surgery Group of the
      German Trauma Society].
AB  - The primary goal in the treatment of carpal fractures is the preservation of a
      painless wrist function. Scaphoid fractures are the most common carpal fractures
      and when such a fracture is clinically suspected CT or MRI scans are usually
      advisable. Only stable and non-displaced scaphoid fractures can be treated
      conservatively, all other fractures require internal fixation with restoration of
      normal anatomy. Second most common are fractures of the triquetrum which can
      occur as chip avulsions of the dorsal rim and are usually treated
      symptomatically. Fractures of the body of the triquetrum should be treated
      according to the degree of instability and displacement. This is virtually true
      for all carpal bones. Perilunate fracture dislocations of the carpus deserve
      special attention. In these severe injuries a fracture line can run through all
      carpal bones but the scaphoid is mostly affected. Accurate reduction and internal
      fixation by screws and K-wires are indicated not only in these cases, but also in
      carpometacarpal fracture dislocations.

PMID- 20824423
TI  - [Angiographic diagnosis of acral circulatory disorders of the upper extremities].
AB  - Acral ischemic lesions rarely affect the upper extremities. While in the lower
      limbs atherosclerosis is responsible for the majority of lesions, vasculitis and
      autoimmune diseases play an important role in the pathogenesis of ischemic
      lesions of the upper limbs. A considerable number of acral circulatory disorders
      present with Raynaud's phenomenon and often without associated necrosis.
      Raynaud's phenomenon is mainly idiopathic but may also be secondary to underlying
      conditions, such as autoimmune diseases and vasculitis. Because of its high
      spatial resolution and the often discrete morphological findings digital
      subtraction angiography (DSA) is still an important diagnostic method in the
      radiological evaluation of acral circulatory disorders of the hand. Angiographic
      features of vasculitis are not strictly pathognomonic but certain morphologic DSA
      findings are very typical and may allow for a radiologic diagnosis. For instance,
      atherosclerosis results in irregular contours of vessel walls in DSA in contrast
      to autoimmune diseases and vasculitis, which are usually characterized by smooth
      vessel walls and optional vasospasm, the latter being especially typical for
      thromboangiitis obliterans and scleroderma. In thromboangiitis obliterans
      occlusions of the distal hand arteries, corkscrew collateral vessels and
      subsequent development of fine collateral networks are typical findings. Abrupt
      or filiform occlusions of distal finger arteries with sparse collateralization
      and symmetric affection of both hands are suggestive of scleroderma. Disseminated
      segmental ectasis and stenosis as well as microaneurysms (63% of all patients)
      are very common in patients with panarteriitis nodosa.

PMID- 20824424
TI  - Comparison of established and novel purity tests for the quality control of
      heparin by means of a set of 177 heparin samples.
AB  - The widespread occurrence of heparin contaminated with oversulfated chrondroitin
      sulfate (OSCS) in 2008 initiated a comprehensive revision process of the
      Pharmacopoeial heparin monographs and stimulated research in analytical
      techniques for the quality control of heparin. Here, a set of 177 heparin samples
      from the market in 2008 as well as pure heparin sodium spiked with defined
      amounts of OSCS and DS were used to evaluate established and novel methods for
      the quality control of heparin. Besides (1)H nuclear magnetic resonance
      spectroscopy (NMR), the assessment included two further spectroscopic methods,
      i.e., attenuated total reflection-infrared spectroscopy (ATR-IR) and Raman
      spectroscopy, three coagulation assays, i.e., activated partial thromboplastin
      time (aPTT) performed with both sheep and human plasma and the prothrombin time
      (PT), and finally two novel purity assays, each consisting of an incubation step
      with heparinase I followed by either a fluorescence measurement (Inc-PolyH-assay)
      or by a chromogenic aXa-assay (Inc-aXa-assay). NMR was shown to allow not only
      sensitive detection, but also quantification of OSCS by using the peak-height
      method and a response factor determined by calibration. Chemometric evaluation of
      the NMR, ATR-IR, and Raman spectra by statistical classification techniques
      turned out to be best with NMR spectra concerning the detection of OSCS. The
      validity of the aPTT, the current EP assay, could be considerably improved by
      replacing the sheep plasma by human plasma. In this way, most of the contaminated
      heparin samples did not meet the novel potency limit of 180 IU/mg. However, also
      more than 50% of the uncontaminated samples had <180 IU/MG. In contrast to the
      aPTT, the PT specifically detects OSCS and other heparin mimetics (LOD 3%). About
      ten times more sensitive are both the Inc-PolyH-assay and the Inc-aXa-assay, two
      rapid and simple quantification assays for heparin mimetics. The determined OSCS
      contents of the heparin samples excellently correlated with those calculated from
      the NMR spectra. In conclusion, NMR proved to be the current spectroscopic method
      of choice. The two two-step-assays represent options to supplement NMR,
      especially as tests for the initial screening, since they detect any heparin
      mimetic without requiring special expertise for interpretation of the results.

PMID- 20824425
TI  - Real-time monitoring of biomolecular interactions in blood plasma using a surface
      plasmon resonance biosensor.
AB  - We report a novel approach to biosensor-based observations of biomolecular
      interactions which enables real-time monitoring of biomolecular interactions in
      complex media. This approach is demonstrated by investigating the interaction
      between the human chorionic gonadotropin (hCG) and its antibody in blood plasma
      using a surface plasmon resonance biosensor and a dispersionless microfluidics
      system. The real-time binding data obtained in blood plasma are compared with
      those obtained in buffer and blood plasma using a conventional method. It is also
      demonstrated that the proposed approach can enhance the capability of the
      biosensor to detect biomolecules in complex samples in terms of detection time
      and sensitivity. In the model experiment, this approach is shown to enable direct
      detection of hCG in blood plasma at levels which are five times lower than those
      detected using the conventional detection approach.

PMID- 20824426
TI  - High-resolution, imaging TOF-SIMS: novel applications in medical research.
AB  - The use of high-resolution, imaging TOF-SIMS is described and examples are made
      to demonstrate the application of the method in medical research. Cytochemistry
      by TOF-SIMS is shown by localization of diacylglycerol (DG) in cryostat sections
      of hyaline cartilage and by localization of corticosterone in cryostat sections
      of the adrenal gland cortex. Quantitative measurements and comparison of groups
      is shown by comparing the lipid content of adipose tissue from two mouse strains,
      transgenic mouse expressing the FOXC2 gene and wild-type controls. Finally,
      biopsies made for histopathological diagnosis of infantile reversible cytochrome
      c oxidase deficiency myopathy were analyzed in order to define the chemical
      content of areas showing a pathological structure in the light microscope. The
      use of high-resolution, imaging TOF-SIMS in medical research allows analysis of
      intact tissue and probe-free localization of specific target molecules in cells
      and tissues. The TOF-SIMS analysis is not dependent on penetration of reagents
      into the sample and also independent of probe reactivity such as cross-reactivity
      or background staining. The TOF-SIMS method can be made quantitative and allows
      for analysis of specific target molecules in defined tissue compartments.

PMID- 20824428
TI  - Towards an unbiased metabolic profiling of protozoan parasites: optimisation of a
      Leishmania sampling protocol for HILIC-orbitrap analysis.
AB  - Comparative metabolomics of Leishmania species requires the simultaneous
      identification and quantification of a large number of intracellular metabolites.
      Here, we describe the optimisation of a comprehensive metabolite extraction
      protocol for Leishmania parasites and the subsequent optimisation of the
      analytical approach, consisting of hydrophilic interaction liquid chromatography
      coupled to LTQ-orbitrap mass spectrometry. The final optimised protocol starts
      with a rapid quenching of parasite cells to 0  degrees C, followed by a
      triplicate washing step in phosphate-buffered saline. The intracellular
      metabolome of 4 * 10(7) parasites is then extracted in cold
      chloroform/methanol/water 20/60/20 (v/v/v) for 1 h at 4  degrees C, resulting in
      both cell disruption and comprehensive metabolite dissolution. Our developed
      metabolomics platform can detect approximately 20% of the predicted Leishmania
      metabolome in a single experiment in positive and negative ionisation mode.

PMID- 20824427
TI  - Selective peracetic acid determination in the presence of hydrogen peroxide using
      a label free enzymatic method based on catalase.
AB  - Peracetic acid (PAA) is selectively determined in the presence of hydrogen
      peroxide (H(2)O(2)) by using the self-indicating UV-Vis molecular absorption
      properties of catalase. The PAA reacts with the protein giving an intermediate
      (Cat-I) which is reduced back by the amino acid core surrounding the heme group.
      Since the original form of the enzyme and the Cat-I have different UV-Vis
      absorption properties, the absorbance changes can be used for PAA determination.
      The H(2)O(2)/catalase reaction is extremely fast so that neither Cat-I compound
      nor kinetic interferences are observed. The method permits PAA determination in
      the 5 * 10(-7) to 1.5 * 10(-5) M range, the reproducibility being between 1% and
      10%. Using this method, PAA has been successfully determined in water samples
      treated with commercial PAA/H(2)O(2) biocides. A theoretical study has also been
      carried out for obtaining a mathematical model able to analytically describe the
      process.

PMID- 20824429
TI  - Normal silica gel and reversed phase thin-layer chromatography coupled with UV
      spectroscopy and IR-MALDI-o-TOF-MS for the detection of tetracycline antibiotics.
AB  - Tetracyclines (TCs) form a group of bacteriostatic antibiotics with closely
      related structures and similar chemical and physicochemical properties. They are
      widely employed as therapeutics in human and veterinary medicine. Here, we
      introduce the combination of UV spectroscopic detection of high-performance thin
      layer chromatography (HPTLC)-separated TCs with direct analysis on solid phase
      using infrared matrix-assisted laser desorption/ionization orthogonal time-of
      flight mass spectrometry (IR-MALDI-o-TOF-MS). Normal silica gel phase- and water
      wettable hybrid C(18) reversed phase layers (RP-18W) both allowed HPTLC
      separation and sensitive UV spectroscopic detection followed by MS analysis of
      distinct TCs bands using the liquid matrix glycerol. The novel approach of direct
      IR-MALDI-o-TOF-MS analysis resulted in the unequivocal identification of four
      structurally different TCs employed in this study, and linear calibration curves
      were produced for analyte amounts from 20 ng to 1 MUg. MS analysis of TCs from RP
      18W HPTLC plates was found to be superior when compared to the spectra acquired
      from the silica gel layer. Ionic analytes obtained from the RP-18W surface are
      mainly detected as protonated species of high abundance accompanied by a reduced
      formation of adducts as well as background ions arising from the matrix or the
      stationary phase. This results in decreased complexity of the spectra and
      enhanced sensitivity of the combinatorial method. An approximate detection limit
      of 5 ng of individual TCs in mixtures by combining RP-18W HPTLC with IR-MALDI-o
      TOF-MS offers a novel timely and cost-efficient method for tracing TCs.

PMID- 20824430
TI  - Analysis of a cholera toxin B subunit (CTB) and human mucin 1 (MUC1) conjugate
      protein in a MUC1-tolerant mouse model.
AB  - Since epithelial mucin 1 (MUC1) is associated with several adenocarcinomas at the
      mucosal sites, it is pertinent to test the efficacy of a mucosally targeted
      vaccine formulation. The B subunit of the Vibrio cholerae cholera toxin (CTB) has
      great potential to act as a mucosal carrier for subunit vaccines. In the present
      study we evaluated whether a MUC1 tandem repeat (TR) peptide chemically linked to
      CTB would break self-antigen tolerance in the transgenic MUC1-tolerant mouse
      model (MUC1.Tg) through oral or parenteral immunizations. We report that oral
      immunization with the CTB-MUC1 conjugate along with mucosal adjuvant,
      unmethylated CpG oligodeoxynucleotide (ODN) and interleukin-12 (IL-12) did not
      break self-antigen tolerance in MUC1.Tg mice, but induced a strong humoral
      response in wild-type C57BL/6 mice. However, self-antigen tolerance in the
      MUC1.Tg mouse model was broken after parenteral immunizations with different
      doses of the CTB-MUC1 conjugate protein and with the adjuvant CpG ODN co
      delivered with CTB-MUC1. Importantly, mice immunized systemically with CpG ODN
      alone and with CTB-MUC1 exhibited decreased tumor burden when challenged with a
      mammary gland tumor cell line that expresses human MUC1.

PMID- 20824431
TI  - [mRNA quantification. The next challenge in routine diagnostics].
AB  - The application of predictive biomarkers results in an increase in the response
      rates and overall survival of cancer patients. This had been shown impressively
      for the detection of mutations in the proto-oncogenes KRAS and EGFR for the
      application of anti-EGFR targeted therapies in metastatic colorectal carcinomas
      and non-small-cell lung cancer, respectively. This mutation detection is of a
      qualitative nature. In addition, predictive biomarkers are known for the use of
      the commonly administered chemotherapeutics 5-fluorouracil, platinum-containing
      complexes, and Irinotecan, which are normally identical to the targets of the
      therapeutic compounds. The determination of these predictive biomarkers also
      results in an increase in response rates and overall survival. However, this
      detection is done via the quantitative determination of mRNA expression levels,
      implying greater efforts in detection, knowledge of cut-off levels, and higher
      requirements for nationwide establishment.

PMID- 20824432
TI  - [Hereditary gastric cancer].
AB  - Hereditary diffuse gastric cancer is an autosomal dominant cancer syndrome with
      approximately 70%-80% penetrance. The cumulative lifetime risk of clinically
      detected gastric cancer is 63%-83% for women and 40%-67% for men. The average age
      at diagnosis is 40 years. Approximately 25%-40% of patients carry a germline
      mutation of the CDH1 gene. This gene encodes the transmembrane protein E-cadherin
      which plays a central role in cell adhesion and signal transduction. Classified
      according to Lauren, patients develop multifocal diffuse signet-ring cell
      carcinoma and, in late stages, linitis plastica. In the foveolar neck region, the
      site of gastric stem cells, in situ signet-ring cell carcinoma has been
      identified as a precursor lesion of invasive cancer. Therein, pagetoid spread of
      tumour cells below the preserved epithelium within the basal membrane represents
      the characteristic morphology. PAS staining may facilitate detection of tiny
      lesions.The present article provides detailed information on this cancer syndrome
      from the point of view of the pathologist as well as the human geneticist,
      focussing on the multidisciplinary management of affected patients.

PMID- 20824433
TI  - [Microsatellite instability. A new predictive marker (?)].
AB  - Microsatellite instability (MSI) is a hallmark of hereditary non-polyposis
      colorectal cancer (HNPCC), but also occurs in about 12%-15% of sporadic
      colorectal cancer (CRC) where it is a consequence of an epigenetic inactivation
      of MLH1. High frequency MSI (MSI-H; i.e. at least two of five specified
      microsatellite markers show instability) was shown in a large meta-analysis and
      in recent trials to be a positive prognostic marker for overall survival in CRC.
      MSI-H or mismatch repair deficiency (MMRD) was also shown to be a marker for
      ineffectiveness of adjuvant 5-fluorouracil (5-FU) based chemotherapy in CRC. At
      present, there are no guidelines defining the need for microsatellite analysis
      before chemotherapy. However, studies published to date provide data suggesting
      that MSI-H CRC patients should not receive adjuvant chemotherapy, with the
      exception of patients with other factors or poor prognosis (e.g. T4 tumors, G3/G4
      status, blood or lymphatic vessel invasion). MSI or MMRD testing can contribute
      to a more individualized therapy of CRC and should be performed prior to planned
      5-FU monotherapy or adjuvant chemotherapy in a non-metastatic setting.

PMID- 20824435
TI  - Statistical process control charts for ophthalmology.

PMID- 20824434
TI  - [DNA methylation. From basic research to routine diagnostics].
AB  - On a molecular level cancer is characterized not only by genetic defects, such as
      deletions, mutations or translocations, but also by epigenetic lesions. The most
      important epigenetic mechanisms are DNA methylation, Polycomb/trithorax
      complexes, histon modifications, non-coding RNAs, and chromosomal territories.
      These epigenetic mechanisms contribute to a stable modification of gene
      expression without changes in primary DNA sequence. During the development and
      progression of human tumours a gene-specific hypermethylation with resulting
      repression of transcription can occur. At the same time, global hypomethylation
      can very often be observed which contributes to an increase in chromosomal
      instability. In tumour pathology, the detection of somatic hMLH1 hypermethylation
      is important for molecular diagnostics of Lynch syndrome. The detection of MGMT
      gene methylation is a good prognostic and predictive factor for glioblastoma
      patients. Performing DNA methylation assays for routine diagnostics requires
      technical as well as theoretical expertise.

PMID- 20824436
TI  - Rare diseases - avoiding misperceptions and establishing realities: the need for
      reliable epidemiological data.
AB  - The rare disease community suffers from the absence of reliable epidemiological
      data on the prevalence and incidence of rare diseases in the national and global
      populations. The rare diseases community includes all of the stakeholders
      involved in the research and development and dissemination of products and
      information for the diagnosis, prevention or treatment of rare diseases or
      conditions. To replace many of the perceived myths with realities, several global
      efforts are required if we are going to sustain and increase the reported
      progress with the thousands of rare diseases. One is the identification and
      expansion of worldwide partnerships and collaborations of Patient Advocacy Groups
      for individual rare diseases. Another requirement is to develop a global research
      infrastructure of qualified investigators to stimulate and coordinate research
      efforts by seeking ways to provide access to clinical trials at multi-national
      research sites with common protocols and multi-disciplinary research teams.
      Providing ready access to the information about rare diseases, patient advocacy
      groups, research studies and products in research protocols will continue to
      improve the lives of patients and their families. Many scientists, public and
      private sector organizations, patient advocacy groups, foundations, and the
      pharmaceutical, biotechnology, and medical devices industries are committed to
      translating research discoveries that will be useful in the care of patients with
      rare diseases over their lifespan. Evidence from well constructed epidemiological
      studies will provide the evidence that point to the value of additional clinical
      studies to increase the understanding of rare diseases.

PMID- 20824438
TI  - Evidence-based medicine and rare diseases.
AB  - This chapter discusses the meaning of evidence-based medicine and where it
      relates to randomised controlled trials, but also where it does not. The need for
      good quality evidence is stressed through a discussion of high failure rates in
      drug development and arguments against access to unlicensed (and largely
      untested) treatments are set out (despite the good intentions of those who
      advocate such access to treatments). Good quality, reliable evidence does not
      always have to come from clinical trials. Other forms of evidence are discussed.
      Meta-analyses of individual trials may help to resolve the problem that, in rare
      diseases, it may be very difficult or impossible to do adequately powered
      clinical trials - but that does not imply those trials have no value at all. The
      importance of patients' choices is stressed but the difficulties of making
      choices and the general poor understanding of risk makes patients very vulnerable
      to making poor decisions. They need to be adequately guided through the evidence
      to make proper informed decisions.

PMID- 20824437
TI  - Rare diseases epidemiology research.
AB  - Rare Diseases Epidemiology is a novel action field still largely unexplored.
      However, Rare Diseases is a topic of growing interest at world level. The aims of
      this chapter are to revise useful epidemiological tools and define areas where
      epidemiology can help improve the rare disease knowledge, and facilitate policy
      decisions taking into account the real burden of rare diseases in society. This
      chapter also seeks to describe: the problems of coding and classification of
      diseases, measuring disease frequency, the study designs and association studies,
      the causality, the evolution from descriptive to epigenetic epidemiology and the
      natural history of disease. One of the major challenges facing analytical
      epidemiology and clinical epidemiological research into rare diseases is that
      genes can be involved in both aetiology and prognosis. Despite the many
      similarities between genetic association studies and classic observational
      epidemiological studies, the former pose several specific limitations, including
      an unprecedented volume of new data and the likelihood of very small individual
      effects, as well other limitations. Selecting the appropriate pathway from among
      all those available, i.e. the one that best relates genes from the various known
      regions and disease mechanisms, is crucial for the success of this type of
      studies.

PMID- 20824439
TI  - Prevention, diagnosis and services.
AB  - This chapter summarizes how prevention, diagnosis and services can result from
      the activities of a research programme on the group of rare diseases constituted
      by congenital anomalies. The Spanish Collaborative Study of Congenital
      Malformations (ECEMC) is a research programme based on a case-control registry of
      consecutive newborn infants with congenital anomalies. Its aim is the prevention
      of this group of rare diseases, through the research on their causes and
      pathogenesis, combined with the translational activity to transfer the benefits
      of this knowledge to the general population and health care providers. Its
      experience could be applied to the research on other rare diseases. The different
      levels of prevention (primary, secondary, tertiary and quaternary) are briefly
      defined, and the way in which these levels are being applied or can be applied to
      congenital defects prevention is reviewed. The main primary prevention measures
      regarding congenital anomalies are also detailed. To this respect, the benefits
      derived from the activity of Teratology Information Services (TIS), for the
      general population as well as for health care providers, are explained. It is
      finally emphasized how the epidemiological data can contribute to the prevention
      of that group of rare diseases.

PMID- 20824440
TI  - The importance of case reports in advancing scientific knowledge of rare
      diseases.
AB  - Case reports are defined as the scientific documentation of a single clinical
      observation and have a time-honored and rich tradition in medicine and scientific
      publication. Case reports represent a relevant, timely, and important study
      design in advancing medical scientific knowledge especially of rare diseases.
      While there are clear limitations to the methodology of case studies in
      determination of treatment and establishment of new tests, the observation of a
      single patient can add to our understanding of etiology, pathogenesis, natural
      history, and treatment of particularly rare diseases, and to the training of
      potential junior investigators. In recent years this class of scientific
      publication has come under scrutiny and disfavor among some in the medical
      scientific publication community and case studies are frequently relegated to the
      lowest rung of the hierarchy of study design. In this chapter the author will
      review and summarize the debate around the scientific publication of case reports
      in the context of the study of rare diseases and will present a taxonomy that
      ideally will encourage further dialogue on the topic. Future research on the
      importance of case reports in advancing knowledge of rare diseases is
      recommended.

PMID- 20824441
TI  - Patient registries: utility, validity and inference.
AB  - Patient registries are essential tools for public health surveillance and
      research inquiry, and are a particularly important resource for understanding
      rare diseases. Registries provide consistent data for defined populations and can
      support the study of the distribution and determinants of various diseases. One
      advantage of registries is the ability to observe caseload and population
      characteristics over time, which might facilitate the evaluation of disease
      incidence, disease etiology, planning, operation and evaluation of services,
      evaluation of treatment patterns, and diagnostic classification. Any registry
      program must collect high quality data to be useful for its stated purpose.
      Registries can be developed for many different needs, and caution should be taken
      in interpreting registry data, which has inherent biases. We describe the
      methodological issues, limitations, and ideal features of registries to support
      various rare disease purposes. The future impact of registries on our
      understanding and interventions for rare diseases will depend upon technological
      and political solutions for global cooperation to achieve consistent data (via
      standards) and regulations for various registry applications.

PMID- 20824442
TI  - Biobanking in rare disorders.
AB  - Biobanks are collections of biomaterials with associated data. Biobanking is an
      essential tool to provide access to high quality human biomaterial for
      fundamental and translational research. Research for rare disorders benefits from
      the provision of human biomaterials through biobanks, and each human sample from
      a person with a rare disorder has a high value as it may hold the key to answer
      an important research question. Transnational cooperation in biobanking is an
      important catalyst to share limited resources and achieve optimal outcomes as in
      other areas of rare disorder research. Networks of biobanks aim to assure common
      practices and quality standards, and facilitate access to rare disorder
      biomaterials for the scientific community.

PMID- 20824443
TI  - Evaluation of the validity and utility of genetic testing for rare diseases.
AB  - The conventional criteria for evaluating genetic tests include analytic validity,
      clinical validity, and clinical utility. Analytical validity refers to a test's
      ability to measure the genotype of interest accurately and reliably. Clinical
      validity refers to a test's ability to detect or predict the clinical disorder or
      phenotype associated with the genotype. Clinical utility of a test is a measure
      of its usefulness in the clinic and resulting changes in clinical endpoints. In
      addition, the utility to individuals and families of genomic information, or
      personal utility, should be considered. This chapter identifies methodological
      and data issues involved in assessing each type of validity or utility. The
      validity and utility of a test must be considered in a specific context, which
      include diagnostic testing, newborn screening, prenatal carrier screening, and
      family or cascade screening. Specific rare disorders addressed include cystic
      fibrosis, fragile X syndrome, Duchenne and Becker muscular dystrophy, spinal
      muscular atrophy, Huntington disease, as well as cancer associated with BRCA
      mutations.

PMID- 20824444
TI  - Population-based surveillance for rare congenital and inherited disorders: models
      and challenges.
AB  - Worldwide, an estimated 7.9 million children are affected by congenital and
      inherited disorders. Some disorders are relatively common, affecting tens of
      thousands of newborns annually; others are rare, involving disorders that, in
      extreme cases, can affect less than 30 infants per year. However, this
      infrequency does not reduce the impact or burden on individuals and their
      families. Congenital defects can cause long-term disability, have a lifelong
      impact on health, and cost billions of dollars in care. Collection of population
      based surveillance data ideally enables the discovery of etiologies for rare
      congenital disorders of unknown cause, allows for examining outcomes, and
      evaluating treatments and interventions for children with all types of congenital
      and inherited disorders. Many challenges are associated with performing
      population-based surveillance, such as difficulty in ascertaining appropriate
      diagnoses and frequent unavailability of necessary resources. This chapter
      focuses on the importance of population-based data and uses national and
      international surveillance systems as models for how these rare disorders can be
      better understood.

PMID- 20824445
TI  - Statistical methods for the geographical analysis of rare diseases.
AB  - In this chapter we provide a summary of different methods for the detection of
      disease clusters. First of all, we give a summary of methods for computing
      estimates of the relative risk. These estimates provide smoothed values of the
      relative risks that can account for its spatial variation. Some methods for
      assessing spatial autocorrelation and general clustering are also discussed to
      test for significant spatial variation of the risk. In order to find the actual
      location of the clusters, scan methods are introduced. The spatial scan statistic
      is discussed as well as its extension by means of Generalised Linear Models that
      allows for the inclusion of covariates and cluster effects. In this context, zero
      inflated models are introduced to account for the high number of zeros that
      appear when studying rare diseases. Finally, two applications of these methods
      are shown using data of Systemic Lupus Erythematosus in Spain and brain cancer in
      Navarre (Spain).

PMID- 20824446
TI  - Clinical trials and rare diseases.
AB  - Whenever possible, standard methodological approaches should be applied in the
      design and analysis of a clinical trial that warrant adequate informative value.
      However, there are circumstances when the number of experimental subjects is
      unavoidably small. In such circumstances it is justified to consider abandoning
      standard statistical methodology in place of alternative approaches. Performing a
      small clinical trial however it should be pointed out, that a such trial can
      never be as meaningful and provide as much evidence as a larger trial. In the
      present text, basic concepts are presented, that apply to small clinical trials
      in general. Moreover, several specific methodological approaches are presented,
      that either enhance the efficiency of standard statistical procedures or evolve
      from the idea of abandoning classical paradigms in the design and analysis of
      clinical trials. Within the scope of the former approach, (Bayesian) adaptive
      randomisation, group sequential (adaptive) designs, repeated measurement designs
      for longitudinal data, and meta-analyses are illustrated and discussed. The
      latter approach comprises alternative strategies such as (non-randomised) risk
      based allocation designs, statistical prediction designs, ranking and selection
      designs, as well as the application of Bayesian statistics.

PMID- 20824447
TI  - A regulatory overview about rare diseases.
AB  - Rare diseases attract very little interest for drug development. To create more
      favourable conditions, incentives for development (scientific advice, research
      grants) and marketing of medicines (market exclusivity, regulatory fee
      reductions) are offered by several orphan legislations. These incentives have
      proven to be a valuable stimulus for research and development for new products
      for treatment, prevention and diagnosis of rare diseases. In the US almost 2000
      products have been designated as orphan medicines and about 340 have received
      marketing authorisation. Rare diseases have also gained attention from regulators
      in the last years. Nowadays it is acknowledged that rare diseases deserve
      specific attention and individual regulatory guidance. Also, regulatory
      authorities have developed different mechanisms to put products on the market
      considering specific limitations of data availability (conditional marketing
      authorisation, exceptional circumstances authorisation). In the future more
      initiatives will have to address the need for networking scientific knowledge and
      research capabilities to address the difficulties to generate data in rare
      diseases.

PMID- 20824448
TI  - Economic considerations in the provision of treatments for rare diseases.
AB  - Orphan Drug legislation in the USA, Europe and elsewhere has been incredibly
      successful in promoting the development of new treatments for rare diseases.
      Historically, payers have constructed special schemes that have facilitated
      patient access given the small total budget impact of these treatments. However,
      whilst each disease is rare, the number of licensed orphan drugs is growing
      rapidly. This, in conjunction with the high prices claimed for these treatments,
      has increased the total budget impact of orphan drugs. In the medium term, the
      feasibility of omitting orphan drugs from value for money type assessments is
      doubtful. The arguments for a special status for orphan drugs in reimbursement
      processes are reviewed in this article, and it is concluded that these arguments
      do not generally stand up to critical assessment. A new paradigm for the
      development and purchase of orphan drugs may be required. Given the strong
      parallels between the challenges of neglected diseases in developing countries
      and orphan diseases in developed countries, policy tools developed for neglected
      diseases; such as Public Private Partnerships and Advance Market Commitments,
      might be fruitfully applied in the orphan drug arena.

PMID- 20824449
TI  - Rare diseases social epidemiology: analysis of inequalities.
AB  - Rare disease patients experience particular obstacles in accessing high quality
      healthcare. These obstacles include but are not limited to: (i) lack of
      scientific knowledge of their disease, (ii) lack of access to correct diagnosis,
      (iii) delays in diagnosis, (iv) lack of appropriate multidisciplinary healthcare,
      (v) lack of quality information and support at the time of diagnosis, (vi) undue
      social consequences, (vii) inequities and difficulties in access to treatment,
      rehabilitation and care, (viii) dissatisfaction with and loss of confidence in
      medical and social services, (ix) denied treatment by health professionals and
      (x) lack of availability of orphan drugs. Three surveys and their subsequent
      analysis, conducted by the European Organisation for Rare Diseases (EURORDIS), a
      non-governmental patient driven alliance of European patient organisations,
      demonstrate several of these obstacles by describing the experience of rare
      disease patients across 18 rare diseases and over 24 European countries as well
      as highlighting inequalities that exist between them.

PMID- 20824450
TI  - Quality of life and rare diseases.
AB  - HRQOL assessment in patients with rare diseases can help to identify health
      needs, to evaluate the impact of disease and treatments, and to assess the
      evolution in health status through the natural history of disease. Several
      studies have shown that although some rare diseases do not necessarily affect
      life expectancy, the majority lead to physical, emotional and/or psychosocial
      limitations with a wide range of disabilities. Reliability as well as content,
      criterion, and construct validity, and also responsiveness should be taken into
      account in selecting the instrument to be used assessing individuals with rare
      diseases. The use of proxy-report may be essential in some cases where the
      patient is cognitively impaired or unable to communicate. Criteria for selecting
      a HRQOL instrument, as well as the more common strategies proposed help interpret
      scores on HRQOL instruments are addressed in the chapter. Given the impact of
      rare diseases on the quality of life of both patients and carers, it is likely
      that interest in its measurement will continue to increase among professionals,
      patients, and the general public. Improving the quality of life of people with
      rare diseases should be one of the most important goals of any health care
      intervention or multidisciplinary approach.

PMID- 20824451
TI  - Cost of illness and economic evaluation in rare diseases.
AB  - Rare diseases are a major cause of morbidity and mortality in high income
      countries and have major repercussions on individuals and health care systems.
      This chapter examines the health economy of rare diseases from two different
      perspectives: firstly, the study of the economic impact of rare diseases (Cost of
      Illness studies); and, secondly, cost-effectiveness evaluation, which evaluates
      both the costs and results of the health care technologies applied in rare
      diseases. From the point of view of economics, health resource allocation is
      based on the principle of scarcity, as there are not - and never will be-
      sufficient resources for all worthy objectives. Hence, policy makers should
      balance costs and health outcomes. Rare diseases may well represent a significant
      societal burden that should rightly receive appropriate prioritisation of health
      care resources. As new and seemingly expensive health care technologies are
      developed for rare diseases, it will become increasingly important to evaluate
      potential and real impact of these new technologies in both dimensions: social
      costs and health outcomes.

PMID- 20824453
TI  - Hereditary channelopathies in neurology.
AB  - Ion channelopathies are caused by malfunction or altered regulation of ion
      channel proteins due to hereditary or acquired protein changes. In neurology,
      main phenotypes include certain forms of epilepsy, ataxia, migraine, neuropathic
      pain, myotonia, and muscle weakness including myasthenia and periodic paralyses.
      The total prevalence of monogenic channelopathies in neurology is about
      35:100,000. Susceptibility-related mutations further increase the relevance of
      channel genes in medicine considerably. As many disease mechanisms have been
      elucidated by functional characterization on the molecular level, the
      channelopathies are regarded as model disorders for pathogenesis and treatment of
      non-monogenic forms of epilepsy and migraine. As more than 35% of marketed drugs
      target ion channels, there is a high chance to identify compounds that counteract
      the effects of the mutations.

PMID- 20824452
TI  - The burden of rare cancers in Europe.
AB  - The burden of rare tumors in Europe is still unknown and no generally accepted
      definition of them exist. The Surveillance of Rare Cancers in Europe project
      (funded by the European Commission) aimed at providing a definition of "rare
      cancer", a list of cancers and rare cancer burden indicators, based on population
      based cancer registry data, across Europe. An international consensus group
      agreed that incidence is the most appropriate indicator for measuring rare
      cancers frequency and set the threshold for rarity at 6/100,000/year. The list of
      rare cancers was based on the International Classification of Diseases for
      Oncology (ICD-O 3rd edition) and it was hierarchically structured in 2 layers
      based on various combinations of ICD-O morphology and topography codes: layer (1)
      families of tumors (relevant for the health care organisation) and layer (2)
      tumors clinically meaningful (relevant for clinical decision making and
      research). The burden indicators were estimated and are provided in this chapter.

PMID- 20824454
TI  - Osteochondral diseases and fibrodysplasia ossificans progressiva.
AB  - Osteochondrodysplasias like thanatophoric dysplasia, osteogenesis imperfecta,
      achondroplasia, and other genetic skeletal disorders like fibrodysplasia
      ossificans progressiva are infrequently seen in clinical practice. In cases of
      sporadic achondroplasia as well as in fibrodysplasia ossificans progressiva,
      there is a strong association with paternal age, a relationship that is less
      evident in other genetic osteochondral diseases. No other constitutional or
      environmental factor has proven to be associated with these disorders. The use of
      prenatal ultrasonography as a routine component of prenatal care is crucial in
      the early suspicion of osteochondrodysplasias whereas definitive diagnosis is
      usually obtained by pre-natal molecular analysis. In the case of fibrodysplasia
      ossificans progressiva, recognition of congenital great toe malformations
      associated with rapidly-appearing soft tissue swelling is sufficient to make the
      proper clinical diagnosis, which can be confirmed by genetic testing. Large
      regional centres will improve diagnosis performance, provide accurate genetic
      counselling, and ensure an integral assistance for these often severe and
      incapacitating conditions.

PMID- 20824455
TI  - The prevalence of congenital anomalies in Europe.
AB  - EUROCAT (European Surveillance of Congenital Anomalies) is the network of
      population-based registers of congenital anomaly in Europe, with a common
      protocol and data quality review, covering 1.5 million annual births in 22
      countries. EUROCAT recorded a total prevalence of major congenital anomalies of
      23.9 per 1,000 births for 2003-2007. 80% were livebirths. 2.5% of livebirths with
      congenital anomaly died in the first week of life. 2.0% were stillbirths or fetal
      deaths from 20 weeks gestation. 17.6% of all cases were terminations of pregnancy
      following prenatal diagnosis (TOPFA). Thus, congenital anomalies overwhelmingly
      concern children surviving the early neonatal period, who have important medical,
      social or educational needs. The prevalence of chromosomal anomalies was 3.6 per
      1,000 births, contributing 28% of stillbirths/fetal deaths from 20 weeks
      gestation with congenital anomaly, and 48% of all TOPFA. Congenital heart defects
      (CHD) were the most common non-chromosomal subgroup, at 6.5 per 1,000 births,
      followed by limb defects (3.8 per 1,000), anomalies of urinary system (3.1 per
      1,000) and nervous system defects (2.3 per 1,000). In 2004, perinatal mortality
      associated with congenital anomaly was 0.93 per 1,000 births, and TOPFA 4.4 per
      1,000 births, with considerable country variation. Primary prevention of
      congenital anomalies in the population based on controlling environmental risk
      factors is a crucial policy priority, including preconceptional care and whole
      population approaches.

PMID- 20824456
TI  - Rare autoimmune diseases.
AB  - Under the term "autoimmune diseases" are comprised a large number of disorders
      with variable clinical expression which have in common an autoimmune pathogenesis
      as defined by direct, indirect or circumstantial evidence. Autoimmune diseases
      may affect a single organ or may determine a multisystem involvement, and most of
      them cause significant and chronic morbidity and disability. Another important
      feature of autoimmune diseases is their propensity to affect more often females
      than males. Although few of them are quite common and well studied, the majority
      of autoimmune diseases are rare, and share with rare diseases lack of
      epidemiology data. The implementation of specific disease registries can help
      improve the knowledge on epidemiology of these conditions, a crucial step for
      evaluating health care interventions.

PMID- 20824457
TI  - Epidemiology of rare anaemias in Europe.
AB  - Registry and epidemiological data of Rare Anaemias (RA) in Europe is in general
      still incomplete and/or partially documented. One important issue is the
      increasing prevalence of haemoglobin disorders (HD) due to migrations from high
      prevalence areas. The size of the problem, particularly for sickle cell disease
      (SCD), is already having an impact on health services in many European countries.
      The best known cause of rare anaemias associated with congenital haemolytic
      anaemia (CHA) in Europe is Hereditary Spherocytosis (HS) a red blood cell (RBC)
      membrane defect with a prevalence of 1 to 5 cases per 10.000 individuals. Some
      other causes of CHA are extremely rare and only few individual cases have been
      described worldwide (i.e. some RBC enzymopathies). Congenital defects of
      erythropoiesis are less frequent Diamond-Blackfan Anaemia (DBA) and Fanconi
      Anaemia (FA) exhibit a very low prevalence ranging from 4 to 7 per million live
      births. Congenital Dyserythropoietic Anaemia (CDA), a genetically heterogenous
      group, is still less frequent and exhibits a large variability of frequency
      depending on the European region: 0.1-3.0 cases per million births In addition
      many cases are known from a large autosomal dominant family in Sweden. Although
      incidence of Paroxysmal Nocturnal Haemoglobinuria (PNH) in Europe is still
      unknown, data collection from different sources has given quotes of 1 case per
      100,000 individuals to 5 cases per million births.

PMID- 20824458
TI  - Inherited metabolic rare disease.
AB  - Inherited metabolic disorders (IMD) represent a vast, diverse and heterogeneous
      collection of around 700 genetic diseases. They are caused by rare mutations that
      affect the function of individual proteins and are a significant cause of
      morbidity and mortality, especially in childhood. Difficulties in ascertaining
      cases and the increasing number of new disorders have hampered efforts to
      accumulate exhaustive epidemiological data. Nonetheless, recent studies quote the
      cumulative incidence of IMDs at around 1 in 800 live births. To understand the
      epidemiology of IMD we will consider in this chapter two types of epidemiological
      approaches. The first type, or the Analytical approaches, includes the function
      of genetic factors in the natural history and clinical variability of the
      disease, as well as the role of epigenetic, stochastic and environmental factors.
      The second type, or the Descriptive approaches, comprises methods of case
      ascertainment through the diagnosis of symptomatic patients and population
      screening, mainly newborn and carrier screening, as well as measures of disease
      frequency and resources for disease control and prevention (primary, secondary
      and tertiary).

PMID- 20824459
TI  - The contribution of rare diseases to understanding the epidemiology of
      neurodevelopmental disabilities.
AB  - Our objective is to describe the contribution of rare diseases to our
      understanding of the epidemiology of neurodevelopmental disabilities (NDDs) by
      comparing and contrasting the epidemiologic features of NDDs classified according
      to key characteristics of developmental delay or deviance in such areas as
      behavior or cognition (the phenotypic approach; autism spectrum disorders and
      intellectual disability as examples) versus classification based on the
      identification of an etiologic diagnosis (the etiologic approach; 22q11.2
      deletion syndrome and fragile X syndrome as examples). We suggest specific
      applications in which consideration of rare etiology-based NDDs might further our
      understanding of NDD epidemiology overall; what is needed to integrate the two
      classification approaches; and identify practical challenges in achieving that
      integration. Understanding commonalities and differences in the epidemiologic
      features of the phenotypically and etiologically defined NDD classifications
      provides a useful framework for furthering our understanding of the prevalence,
      distribution, and causes of NDDs, as well as delivering appropriate diagnostic
      resources, appropriate treatments, accurate prognostic information, and estimates
      of recurrence risk for these disorders.

PMID- 20824460
TI  - Creating a European Union framework for actions in the field of rare diseases.
AB  - Rare diseases, including those of genetic origin, are defined by the European
      Union as life-threatening or chronically debilitating diseases which are of such
      low prevalence (less than 5 per 10,000). The specificities of rare diseases -
      limited number of patients and scarcity of relevant knowledge and expertise -
      single them out as a unique domain of very high European added-value. The legal
      instruments at the disposal of the European Union, in terms of the Article 152 of
      the Treaties of the European Union, are very limited. However a combination of
      instruments using the research and the pharmaceutical legal basis and an
      intensive and creative use of funding from the First Public Health Programme 2003
      2008 and from the Second Health Programme 2008-2013 has permitted to create a
      solid basis that Member States have considered enough to put rare diseases in a
      privileged position in the health agenda. The adoption of the Commission
      Communication, in November 2008, and of the Council Recommendation, in June 2009,
      and the future adoption of the Directive on Cross-border healthcare, maybe during
      2010, have created an operational framework to act in the field of rare disease
      with European coordination in several areas (classification and codification,
      European Reference Networks, orphan drugs, European Committee of Experts, etc.).
      In conclusion, Rare diseases is an area with enormous and practical
      potentialities for the European cooperation.

PMID- 20824461
TI  - National plans and strategies on rare diseases in Europe.
AB  - This analysis of national plans and strategies on RD in Europe shows that a few
      countries have already set up national plans. Existing national plans show a good
      consistency, but also a quite different stage of progress, depending on start
      date as well as on resource allocation. Several other EU countries have launched
      actions on RD, often with a considerable strategic effort; however, such
      initiatives are yet not integrated in a consistent national strategy taking into
      account the EC recommendations. The project EUROPLAN represents a major
      initiative to support the development of a shared strategy on RD at EU and Member
      State level; critical steps include the comparative evaluation of existing plans
      and actions, identification of gaps and achievements, the development of
      consensus indicators, as well as the integration of successful national
      achievements within the EU strategy.

PMID- 20824462
TI  - Ethical aspects on rare diseases.
AB  - In this chapter we discuss several of the most relevant subjects related to
      ethics on Rare Diseases. Some general aspects are discussed such as the socio
      psychological problems that confront the patients and their families that finally
      lead to marginalization and exclusion of patients affected by these diseases from
      the health programs, even in wealthy countries. Then we address problems related
      to diagnosis and some ethical aspects of newborn screening, prenatal, pre
      implantation diagnosis and reference centers, as well as some conditions that
      should be met by the persons and institutions performing such tasks. Alternatives
      of solutions for the most critical situations are proposed. Subsequently the
      orphan drugs subject is discussed not only from the availability point of view,
      prizes, industrial practices, and purchasing power in developed and developing
      societies. The research related to rare disease in children and other especially
      vulnerable conditions, the need for informed consent, review boards or ethics
      comities, confidentiality of the information, biobanks and pharmacogenetics are
      discussed.

PMID- 20824463
TI  - Advocacy groups and their role in rare diseases research.
AB  - One of the remarkable and unique aspects of the recent history of rare disease
      research has been the evolving role of patient advocacy groups and the
      collaborative partnership that exists among such groups and the scientists who
      study rare diseases, as well as the government officials charged with overseeing
      medical research and regulatory processes. This collaboration, which in many
      respects developed out of necessity on all sides, is unparalleled in other areas
      of medical research and product development. It has played a significant role
      over the past 30 years in the adoption of public policies, available research
      funding and other factors affecting the general climate for research on rare
      diseases. Specific areas of interest include the adoption of the Orphan Drug Act
      in the U.S. in 1983 and subsequent similar legislation elsewhere in the world;
      the relationship of patient advocacy groups with government research funding and
      regulatory entities; the role of patient advocacy groups in seeking to "de-risk"
      orphan product development through initiatives such as facilitating patient
      registries and disease natural histories; the role of advocacy groups in ensuring
      that patients have access to treatments; and the increasing globalization of
      patient advocacy initiatives.

PMID- 20824464
TI  - Proteomics and systems biology: application in drug discovery and development.
AB  - Studies of complex biological systems aimed at understanding their functions at a
      global level are the goals of systems biology. Proteomics, generally regarded as
      the comprehensive study of the expression of all the proteins at a particular
      time in different organs, tissues, and cell types is a key enabling technology
      for the systems biology approach. Rapid advances in this regard have been made
      following the success of the human genome project as well as those of various
      animals and microorganisms. Possibly, one of the most promising outcomes from
      studies on the human genome and proteome is the identification of potential new
      drugs for the treatment of different diseases and tailoring the drugs for
      individualized patient therapy. Following the identification of a new drug
      candidate, knowledge on organ and system-level responses helps prioritize the
      drug targets and design clinical trials based on their efficacy and safety.
      Toxicoproteomics is playing an important role in that respect. In essence, over
      the past decade, proteomics has played a major role in drug discovery and
      development. In this review article, we explain systems biology, discuss the
      current proteomic technologies, and highlight some important applications of
      proteomics and systems biology approaches in drug discovery and development.

PMID- 20824465
TI  - Systems biology approaches and tools for analysis of interactomes and multi
      target drugs.
AB  - Systems biology is essentially a proteomic and epigenetic exercise because the
      relatively condensed information of genomes unfolds on the level of proteins. The
      flexibility of cellular architectures is not only mediated by a dazzling number
      of proteinaceous species but moreover by the kinetics of their molecular changes:
      The time scales of posttranslational modifications range from milliseconds to
      years. The genetic framework of an organism only provides the blue print of
      protein embodiments which are constantly shaped by external input. Indeed,
      posttranslational modifications of proteins represent the scope and velocity of
      these inputs and fulfil the requirements of integration of external
      spatiotemporal signal transduction inside an organism. The optimization of
      biochemical networks for this type of information processing and storage results
      in chemically extremely fine tuned molecular entities. The huge dynamic range of
      concentrations, the chemical diversity and the necessity of synchronisation of
      complex protein expression patterns pose the major challenge of systemic analysis
      of biological models. One further message is that many of the key reactions in
      living systems are essentially based on interactions of moderate affinities and
      moderate selectivities. This principle is responsible for the enormous
      flexibility and redundancy of cellular circuitries. In complex disorders such as
      cancer or neurodegenerative diseases, which initially appear to be rooted in
      relatively subtle dysfunctions of multimodal physiologic pathways, drug discovery
      programs based on the concept of high affinity/high specificity compounds ("one
      target, one-disease"), which has been dominating the pharmaceutical industry for
      a long time, increasingly turn out to be unsuccessful. Despite improvements in
      rational drug design and high throughput screening methods, the number of novel,
      single-target drugs fell much behind expectations during the past decade, and the
      treatment of "complex diseases" remains a most pressing medical need. Currently,
      a change of paradigm can be observed with regard to a new interest in agents that
      modulate multiple targets simultaneously, essentially "dirty drugs." Targeting
      cellular function as a system rather than on the level of the single target,
      significantly increases the size of the drugable proteome and is expected to
      introduce novel classes of multi-target drugs with fewer adverse effects and
      toxicity. Multiple target approaches have recently been used to design
      medications against atherosclerosis, cancer, depression, psychosis and
      neurodegenerative diseases. A focussed approach towards "systemic" drugs will
      certainly require the development of novel computational and mathematical
      concepts for appropriate modelling of complex data. But the key is the extraction
      of relevant molecular information from biological systems by implementing rigid
      statistical procedures to differential proteomic analytics.

PMID- 20824466
TI  - Systems biology "on-the-fly": SILAC-based quantitative proteomics and RNAi
      approach in Drosophila melanogaster.
AB  - Stable isotope labeling with amino acids in cell culture (SILAC) has become
      increasingly popular as a quantitative proteomics (qProteomics) method. In
      combination with high-resolution mass spectrometry (MS) and new efficient
      algorithms for the analysis of quantitative MS data, SILAC has proven to be a
      potent tool for the in-depth characterization of functional states. QProteomics
      extends transcriptomics analysis in providing comprehensive and unbiased protein
      expression profiles. In this chapter, we describe the use of SILAC procedure in
      combination with RNA interference (RNAi) to characterize loss-of-function
      phenotypes, an example to illustrate how qProteomics can address many of the
      systems-wide approaches previously restricted to the mRNA level. Furthermore, by
      explaining the adaptation of SILAC to a novel cellular model, the Drosophila
      melanogaster Schneider cells SL2, we aim to offer an example enabling the readers
      to apply the same strategy to any other cell culture, specific for their need.

PMID- 20824467
TI  - Systems biology of cell behavior.
AB  - Systems Biology approaches to drug discovery largely focus on the increasing
      understanding of intracellular and cellular circuits, by computational
      representation of a molecular system followed by parameter validation against
      experimental data. This chapter outlines a universal approach to systems biology
      that allows the linking of intracellular molecular machinery and cellular
      activity. This procedure is achieved by applying mathematical modeling to
      molecular modules of a cell in the light of systems biology techniques.

PMID- 20824468
TI  - Computational modeling in systems biology.
AB  - Interactions among cellular constituents play a crucial role in overall cellular
      function and organization. These interactions can be viewed as being
      complementary to the usual "parts list" of genes and proteins and, in conjunction
      with the expression states of these parts, are key to a systems level
      understanding of the cell. Here, we review computational approaches to the
      understanding of the functional roles of cellular networks, ranging from "static"
      models of network topology to dynamical and stochastic simulations.

PMID- 20824469
TI  - An introduction to Gaussian Bayesian networks.
AB  - The extraction of regulatory networks and pathways from postgenomic data is
      important for drug -discovery and development, as the extracted pathways reveal
      how genes or proteins regulate each other. Following up on the seminal paper of
      Friedman et al. (J Comput Biol 7:601-620, 2000), Bayesian networks have been
      widely applied as a popular tool to this end in systems biology research. Their
      popularity stems from the tractability of the marginal likelihood of the network
      structure, which is a consistent scoring scheme in the Bayesian context. This
      score is based on an integration over the entire parameter space, for which
      highly expensive computational procedures have to be applied when using more
      complex -models based on differential equations; for example, see (Bioinformatics
      24:833-839, 2008). This chapter gives an introduction to reverse engineering
      regulatory networks and pathways with Gaussian Bayesian networks, that is
      Bayesian networks with the probabilistic BGe scoring metric [see (Geiger and
      Heckerman 235-243, 1995)]. In the BGe model, the data are assumed to stem from a
      Gaussian distribution and a normal-Wishart prior is assigned to the unknown
      parameters. Gaussian Bayesian network methodology for analysing static
      observational, static interventional as well as dynamic (observational) time
      series data will be described in detail in this chapter. Finally, we apply these
      Bayesian network inference methods (1) to observational and interventional flow
      cytometry (protein) data from the well-known RAF pathway to evaluate the global
      network reconstruction accuracy of Bayesian network inference and (2) to dynamic
      gene expression time series data of nine circadian genes in Arabidopsis thaliana
      to reverse engineer the unknown regulatory network topology for this domain.

PMID- 20824470
TI  - Derivation of large-scale cellular regulatory networks from biological time
      series data.
AB  - Pharmacological agents and other perturbants of cellular homeostasis appear to
      nearly universally affect the activity of many genes, proteins, and signaling
      pathways. While this is due in part to nonspecificity of action of the drug or
      cellular stress, the large-scale self-regulatory behavior of the cell may also be
      responsible, as this typically means that when a cell switches states, dozens or
      hundreds of genes will respond in concert. If many genes act collectively in the
      cell during state transitions, rather than every gene acting independently,
      models of the cell can be created that are comprehensive of the action of all
      genes, using existing data, provided that the functional units in the model are
      collections of genes. Techniques to develop these large-scale cellular-level
      models are provided in detail, along with methods of analyzing them, and a brief
      summary of major conclusions about large-scale cellular networks to date.

PMID- 20824471
TI  - Translational bioinformatics and systems biology approaches for personalized
      medicine.
AB  - Systems biology and pharmacogenomics are emerging and promising fields that will
      provide a thorough understanding of diseases and enable personalized therapy.
      However, one of the most significant obstacles in the practice of personalized
      medicine is the translation of scientific discoveries into better therapeutic
      outcomes. Translational bioinformatics is a powerful method to bridge the gap
      between systems biology research and clinical practice. This goal can be achieved
      through providing integrative methods to enable predictive models for therapeutic
      responses. As a media between bench and bedside, translational bioinformatics has
      the mission to meet challenges in the development of personalized medicine. On
      the biomedical side, translational bioinformatics would enable the identification
      of biomarkers based on systemic analyses. It can improve the understanding of the
      correlations between genotypes and phenotypes. It would enable novel insights of
      interactions and interrelationships among different parts in a whole system. On
      the informatics side, methods based on data integration, data mining, and
      knowledge representation can provide decision support for both researchers and
      clinicians. Data integration is not only for better data access, but also for
      knowledge discovery. Decision support based on translational bioinformatics means
      better information and workflow management, efficient literature and resource
      retrieval, and communication improvement. These approaches are crucial for
      understanding diseases and applying personalized therapeutics at systems levels.

PMID- 20824472
TI  - Systems biology and inflammation.
AB  - Inflammation is a complex, multiscale biological response to threats - both
      internal and external - to the body, which is also required for proper healing of
      injured tissue. In turn, damaged or dysfunctional tissue stimulates further
      inflammation. Despite continued advances in characterizing the cellular and
      molecular processes involved in the interactions between inflammation and tissue
      damage, there exists a significant gap between the knowledge of mechanistic
      pathophysiology and the development of effective therapies for various
      inflammatory conditions. We have suggested the concept of translational systems
      biology, defined as a focused application of computational modeling and
      engineering principles to pathophysiology primarily in order to revise clinical
      practice. This chapter reviews the existing, translational applications of
      computational simulations and related approaches as applied to inflammation.

PMID- 20824473
TI  - Immunoinformatics and systems biology methods for personalized medicine.
AB  - The immune system plays an important role in the development of personalized
      medicine for a variety of diseases including cancer, autoimmune diseases, and
      infectious diseases. Immunoinformatics, or computational immunology, is an
      emerging area that provides fundamental methodologies in the study of immunomics,
      that is, immune-related genomics and proteomics. The integration of
      immunoinformatics with systems biology approaches may lead to a better
      understanding of immune-related diseases at various systems levels. Such methods
      can contribute to translational studies that bring scientific discoveries of the
      immune system into better clinical practice. One of the most intensely studied
      areas of the immune system is immune epitopes. Epitopes are important for disease
      understanding, host-pathogen interaction analyses, antimicrobial target
      discovery, and vaccine design. The information about genetic diversity of the
      immune system may help define patient subgroups for individualized vaccine or
      drug development. Cellular pathways and host immune-pathogen interactions have a
      crucial impact on disease pathogenesis and immunogen design. Epigenetic studies
      may help understand how environmental changes influence complex immune diseases
      such as allergy. High-throughput technologies enable the measurements and
      catalogs of genes, proteins, interactions, and behavior. Such perception may
      contribute to the understanding of the interaction network among humans,
      vaccines, and drugs, to enable new insights of diseases and therapeutic
      responses. The integration of immunomics information may ultimately lead to the
      development of optimized vaccines and drugs tailored to personalized prevention
      and treatment. An immunoinformatics portal containing relevant resources is
      available at http://immune.pharmtao.com.

PMID- 20824474
TI  - Systems biology approaches to the study of cardiovascular drugs.
AB  - Atherogenic lipids and chronic inflammation drive the development of
      cardiovascular disorders such as atherosclerosis. Many cardiovascular drugs
      target the liver which is involved in the formation of lipid and inflammatory
      risk factors. With robust systems biology tools and comprehensive bioinformatical
      packages becoming available and affordable, the effect of novel treatment
      strategies can be analyzed more comprehensively and with higher sensitivity. For
      example, beneficial as well as adverse effects of drugs can already be detected
      on the gene and metabolite level, and prior to their macroscopic manifestation.
      This chapter describes a systems approach for a prototype CV drug with
      established beneficial and adverse effects. All relevant steps, for example,
      experimental design, tissue collection and high quality RNA preparation,
      bioinformatical analysis of functional processes, and pathways (targeted and
      untargeted) are addressed.

PMID- 20824475
TI  - Cancer systems biology.
AB  - Cancer is a complex and heterogeneous disease, not only at a genetic and
      biochemical level, but also at a tissue, organism, and population level. Multiple
      data streams, from reductionist biochemistry in vitro to high-throughput "-omics"
      from clinical material, have been generated with the hope that they encode useful
      information about phenotype and, ultimately, tumour behaviour in response to
      drugs. While these data stand alone in terms of the biology they represent, there
      is the enticing prospect that if incorporated into systems biology models, they
      can help understand complex systems behaviour and provide a predictive framework
      as an additional tool in understanding how tumours change and respond to
      treatment over time. Since these biological data are heterogeneous and frequently
      qualitative rather than quantitative, at the present time a single systems
      biology approach is unlikely to be effective; instead, different computational
      and mathematical approaches should be tailored to different types of data, and to
      each other, in order to test and re-test hypotheses. In time, these models might
      converge and result in usable tractable models which accurately represent human
      cancer. Likewise, biologists and clinicians need to understand what the
      requirements of systems biology are so that compatible data are produced for
      computational modelling. In this review, we describe some theoretical approaches
      (data-driven and process-driven) and experimental methodologies which are being
      used in cancer research and the clinical context where they might be applied.

PMID- 20824477
TI  - Systems biology of influenza: understanding multidimensional interactions for
      personalized prevention and treatment.
AB  - Influenza virus infection is a public health threat worldwide. It is urgent to
      develop effective methods and tools for the prevention and treatment of
      influenza. Influenza vaccines have significant immune response variability across
      the population. Most of the current circulating strains of influenza A virus are
      resistant to anti-influenza drugs. It is necessary to understand how genetic
      variants affect immune responses, especially responses to the HA and NA
      transmembrane glycoproteins. The elucidation of the underlying mechanisms can
      help identify patient subgroups for effective prevention and treatment. New
      personalized vaccines, adjuvants, and drugs may result from the understanding of
      interactions of host genetic, environmental, and other factors. The systems
      biology approach is to simulate and model large networks of the interacting
      components, which can be excellent targets for antiviral therapies. The
      elucidation of host-influenza interactions may provide an integrative view of
      virus infection and host responses. Understanding the host-influenza-drug
      interactions may contribute to optimal drug combination therapies. Insight of the
      host-influenza-vaccine interactions, especially the immunogenetics of vaccine
      response, may lead to the development of better vaccines. Systemic studies of
      host-virus-vaccine-drug-environment interactions will enable predictive models
      for therapeutic responses and the development of individualized therapeutic
      strategies. A database containing such information on personalized and systems
      medicine for influenza is available at http://flu.pharmtao.com.

PMID- 20824476
TI  - Systemic lupus erythematosus: from genes to organ damage.
AB  - Systemic lupus erythematosus (SLE) is a disease characterized by inappropriate
      response to self-antigens. Genetic, environmental and hormonal factors are
      believed to contribute to the development of the disease. We think of SLE
      pathogenesis as occurring in three phases of variable duration. A series of
      regulatory failures during the ontogeny of the immune system lead to the
      emergence of auto-reactive clones and the production of auto-antibodies (phase
      I). As the immune response to self-antigens broadens, the auto-antibody
      repertoire is enriched (phase II) and clinical manifestations eventually ensue
      (phase III). The final result is tissue damage that if not treated will lead to
      the functional failure of such important organs as the kidney and brain.

PMID- 20824478
TI  - Methods in systems biology of experimental methamphetamine drug abuse.
AB  - The use of methamphetamine (METH) as recreational drugs is a growing problem
      worldwide with recent concerns that it might cause long-lasting harmful effects
      to the human brain. METH is an illicit drug that is known to exert neurotoxic
      effects on both dopaminergic and serotonergic neural systems. Our laboratory has
      been studying the biochemical mechanisms underlying METH-induced neurotoxic
      effects both in vivo and in vitro. Our psychoproteomics METH abuse research
      focuses on the global alteration of cortical protein expression in rats treated
      with acute METH. In our analysis, an altered protein expression was identified
      using a multistep protein separation/proteomic platform. Differential changes of
      the selected proteins were further confirmed by quantitative immunoblotting. Our
      study identified 82 differentially expressed proteins, 40 of which were
      downregulated and 42 of which were upregulated post acute METH treatment. In this
      chapter, we describe the current protocols for the neuronal cell culture in vitro
      and the in vivo rat model of acute METH treatment (4 x 10 mg/kg) coupled with the
      description current bioinformatics analysis utilized to analyze the different
      implicated interaction protein/gene maps that reflected on the altered functions
      observed. These methods and protocols are discussed in the paradigm of the acute
      model of METH drug abuse and neuronal cell culture and can be applied on other
      models of substance abuse such as on MDMA or cocaine.

PMID- 20824479
TI  - Systems biology and theranostic approach to drug discovery and development to
      treat traumatic brain injury.
AB  - Traumatic brain injury is a significant disease affecting 1.4 to 2 million
      patients every year in the USA. Currently, there are no FDA-approved therapeutic
      remedies to treat TBI despite the fact that there have been over 200 clinical
      drug trials, all which have failed. These drugs used the traditional single drug
      to-target approach of drug discovery and development. An alternative based upon
      the advances in genomics, proteomics, bioinformatic tools, and systems biology
      software has enabled us to use a Systems Biology-based approach to drug discovery
      and development for TBI. It focuses on disease-relevant converging pathways as
      potential therapeutic intervention points and is accompanied by downstream
      biomarkers that allow for the tracking of drug targeting and appears to correlate
      with disease mitigation. When realized, one is able to envision that a companion
      diagnostic will be codeveloped along the therapeutic compound. This "theranostic"
      approach is perfectly positioned to align with the emerging trend toward
      "personalized medicine".

PMID- 20824480
TI  - Comparison of thermoregulatory responses to heat between Malaysian and Japanese
      males during leg immersion.
AB  - The objective of this study was to investigate thermoregulatory responses to heat
      in tropical (Malaysian) and temperate (Japanese) natives, during 60 min of
      passive heating. Ten Japanese (mean ages: 20.8 +/- 0.9 years) and ten Malaysian
      males (mean ages: 22.3 +/- 1.6 years) with matched morphological characteristics
      and physical fitness participated in this study. Passive heating was induced
      through leg immersion in hot water (42 degrees C) for 60 min under conditions of
      28 degrees C air temperature and 50% RH. Local sweat rate on the forehead and
      thigh were significantly lower in Malaysians during leg immersion, but no
      significant differences in total sweat rate were observed between Malaysians
      (86.3 +/- 11.8 g m(-2) h(-1)) and Japanese (83.2 +/- 6.4 g m(-2) h(-1)) after leg
      immersion. In addition, Malaysians displayed a smaller rise in rectal temperature
      (0.3 +/- 0.1 degrees C) than Japanese (0.7 +/- 0.1 degrees C) during leg
      immersion, with a greater increase in hand skin temperature. Skin blood flow was
      significantly lower on the forehead and forearm in Malaysians during leg
      immersion. No significant different in mean skin temperature during leg immersion
      was observed between the two groups. These findings indicated that regional
      differences in body sweating distribution might exist between Malaysians and
      Japanese during heat exposure, with more uniform distribution of local sweat rate
      over the whole body among tropical Malaysians. Altogether, Malaysians appear to
      display enhanced efficiency of thermal sweating and thermoregulatory responses in
      dissipating heat loss during heat loading. Thermoregulatory differences between
      tropical and temperate natives in this study can be interpreted as a result of
      heat adaptations to physiological function.

PMID- 20824481
TI  - Antiemetics in children receiving chemotherapy. MASCC/ESMO guideline update 2009.
AB  - Only a few studies have been carried out in children on the prevention of
      chemotherapy-induced nausea and vomiting (CINV). 5-HT(3) receptor antagonists
      have been shown to be more efficacious and less toxic than metoclopramide,
      phenothiazines and cannabinoids. Most dose studies are available for the 5-HT(3)
      receptor antagonists ondansetron and granisetron. The new 5-HT(3) receptor
      antagonist palonosetron was evaluated in one comparative study so far showing
      promising activity. Combinations of a 5-HT(3) receptor antagonist and
      dexamethasone showed increased efficacy with respect to a 5-HT(3) receptor
      antagonist alone. All paediatric patients receiving chemotherapy of high or
      moderate emetogenic potential should receive a combination of a 5-HT(3) receptor
      antagonist and dexamethasone to prevent acute emesis. No studies have
      specifically evaluated antiemetic drugs in the prevention of chemotherapy-induced
      delayed and anticipatory emesis in children. The role of the NK1 receptor
      antagonists in children has to be further investigated, although one small study
      is published so far, showing promising activity in the prevention of CINV with
      aprepitant. The new proposed guideline from the Multinational Association of
      Supportive Care in Cancer and the European Society of Clinical Oncology
      summarises the updated data from the literature and takes into consideration the
      existing guidelines.

PMID- 20824483
TI  - Effects of signal level and background noise on spectral representations in the
      auditory nerve of the domestic cat.
AB  - Background noise poses a significant obstacle for auditory perception, especially
      among individuals with hearing loss. To better understand the physiological basis
      of this perceptual impediment, the present study evaluated the effects of
      background noise on the auditory nerve representation of head-related transfer
      functions (HRTFs). These complex spectral shapes describe the directional
      filtering effects of the head and torso. When a broadband sound passes through
      the outer ear en route to the tympanic membrane, the HRTF alters its spectrum in
      a manner that establishes the perceived location of the sound source. HRTF-shaped
      noise shares many of the acoustic features of human speech, while communicating
      biologically relevant localization cues that are generalized across mammalian
      species. Previous studies have used parametric manipulations of random spectral
      shapes to elucidate HRTF coding principles at various stages of the cat's
      auditory system. This study extended that body of work by examining the effects
      of sound level and background noise on the quality of spectral coding in the
      auditory nerve. When fibers were classified by their spontaneous rates, the
      coding properties of the more numerous low-threshold, high-spontaneous rate
      fibers were found to degrade at high presentation levels and in low signal-to
      noise ratios. Because cats are known to maintain accurate directional hearing
      under these challenging listening conditions, behavioral performance may be
      disproportionally based on the enhanced dynamic range of the less common high
      threshold, low-spontaneous rate fibers.

PMID- 20824482
TI  - The Fatigue Symptom Inventory: a systematic review of its psychometric
      properties.
AB  - PURPOSE: Fatigue is one of the most common symptoms experienced by persons with
      chronic illness, including cancer. The effective management of fatigue hinges in
      part on the accuracy and reliability of its measurement. The purpose of this
      study was to review and characterize the use of the 14-item Fatigue Symptom
      Inventory (FSI) in published studies and to evaluate the available evidence for
      its psychometric properties. METHODS: A systematic review of the literature
      identified 55 studies reporting results for the FSI. Data were analyzed to
      characterize internal consistency reliability of multi-item FSI scales and test
      retest reliability. Correlation coefficients were summarized to characterize
      concurrent, convergent, and divergent validity. Standardized effect sizes were
      calculated to characterize the discriminative validity of the FSI and its
      sensitivity to change. RESULTS: Sample sizes across studies ranged from 9-1,756.
      Approximately half of the samples consisted exclusively of females. Alpha
      coefficients for multi-item scales ranged from 0.84-0.96. Most items demonstrated
      low to moderate test-retest correlations. Correlations with other fatigue
      measures ranged from 0.41-0.86. Correlations with depression and anxiety measures
      were positive (range = 0.23-0.76). Correlations with measures of vitality and
      vigor were negative (range = -0.28 to -0.77). Effect sizes for discriminative
      validity and sensitivity to change ranged from small to medium and from small to
      large, respectively. CONCLUSIONS: Findings provide good empirical evidence of the
      usefulness of the FSI and strongly support its use in future studies.

PMID- 20824484
TI  - Improving ethanol productivity by modification of glycolytic redox factor
      generation in glycerol-3-phosphate dehydrogenase mutants of an industrial ethanol
      yeast.
AB  - The GPD2 gene, encoding NAD(+)-dependent glycerol-3-phosphate dehydrogenase in an
      industrial ethanol-producing strain of Saccharomyces cerevisiae, was deleted. And
      then, either the non-phosphorylating NADP(+)-dependent glyceraldehyde-3-phosphate
      dehydrogenase (GAPN) from Bacillus cereus, or the NADP(+)-dependent
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Kluyveromyces lactis, was
      expressed in the obtained mutant AG2 deletion of GPD2, respectively. The
      resultant recombinant strain AG2A (gpd2Delta P (PGK)-gapN) exhibited a 48.70 +/-
      0.34% (relative to the amount of substrate consumed) decrease in glycerol
      production and a 7.60 +/- 0.12% (relative to the amount of substrate consumed)
      increase in ethanol yield, while recombinant AG2B (gpd2Delta P (PGK)-GAPDH)
      exhibited a 52.90 +/- 0.45% (relative to the amount of substrate consumed)
      decrease in glycerol production and a 7.34 +/- 0.15% (relative to the amount of
      substrate consumed) increase in ethanol yield compared with the wild-type strain.
      More importantly, the maximum specific growth rates (MU (max)) of the recombinant
      AG2A and AG2B were higher than that of the mutant gpd2Delta and were
      indistinguishable compared with the wild-type strain in anaerobic batch
      fermentations. The results indicated that the redox imbalance of the mutant could
      be partially solved by expressing the heterologous genes.

PMID- 20824485
TI  - Fermentation of xylose into ethanol by a new fungus strain Pestalotiopsis sp. XE
      1.
AB  - A new fungus, Pestalotiopsis sp. XE-1, which produced ethanol from xylose with
      yield of 0.47 g ethanol/g of consumed xylose was isolated. It also produced
      ethanol from arabinose, glucose, fructose, mannose, galactose, cellobiose,
      maltose, and sucrose with yields of 0.38, 0.47, 0.45, 0.46, 0.31, 0.25, 0.31, and
      0.34 g ethanol/g of sugar consumed, respectively. It produced maximum ethanol
      from xylose at pH 6.5, 30 degrees C under a semi-aerobic condition. Acetic acid
      produced in xylose fermenting process inhibited ethanol production of XE-1. The
      ethanol yield in the pH-uncontrolled batch fermentation was about 27% lower than
      that in the pH-controlled one. The ethanol tolerance of XE-1 was higher than most
      xylose-fermenting, ethanol-producing microbes, but lower than Saccharomyces
      cerevisiae and Hansenula polymorpha. XE-1 showed tolerance to high concentration
      of xylose, and was able to grow and produce ethanol even when it was cultivated
      in 97.71 g/l xylose.

PMID- 20824486
TI  - A symbiotic gas exchange between bioreactors enhances microalgal biomass and
      lipid productivities: taking advantage of complementary nutritional modes.
AB  - This paper describes the association of two bioreactors: one photoautotrophic and
      the other heterotrophic, connected by the gas phase and allowing an exchange of
      O(2) and CO(2) gases between them, benefiting from a symbiotic effect. The
      association of two bioreactors was proposed with the aim of improving the
      microalgae oil productivity for biodiesel production. The outlet gas flow from
      the autotrophic (O(2) enriched) bioreactor was used as the inlet gas flow for the
      heterotrophic bioreactor. In parallel, the outlet gas flow from another
      heterotrophic (CO(2) enriched) bioreactor was used as the inlet gas flow for the
      autotrophic bioreactor. Aside from using the air supplied from the auto- and
      hetero-trophic bioreactors as controls, one mixotrophic bioreactor was also
      studied and used as a model, for its claimed advantage of CO(2) and organic
      carbon being simultaneously assimilated. The microalga Chlorella protothecoides
      was chosen as a model due to its ability to grow under different nutritional
      modes (auto, hetero, and mixotrophic), and its ability to attain a high biomass
      productivity and lipid content, suitable for biodiesel production. The comparison
      between heterotrophic, autotrophic, and mixotrophic Chlorella protothecoides
      growth for lipid production revealed that heterotrophic growth achieved the
      highest biomass productivity and lipid content (>22%), and furthermore showed
      that these lipids had the most suitable fatty acid profile in order to produce
      high quality biodiesel. Both associations showed a higher biomass productivity
      (10-20%), when comparing the two separately operated bioreactors (controls) which
      occurred on the fourth day. A more remarkable result would have been seen if in
      actuality the two bioreactors had been inter-connected in a closed loop. The
      biomass productivity gain would have been 30% and the lipid productivity gain
      would have been 100%, as seen by comparing the productivities of the symbiotic
      assemblage with the sum of the two bioreactors operating separately (controls).
      These results show an advantage of the symbiotic bioreactors association towards
      a cost-effective microalgal biodiesel production.

PMID- 20824487
TI  - Biorefining of wood: combined production of ethanol and xylanase from waste fiber
      sludge.
AB  - The possibility to utilize fiber sludge, waste fibers from pulp mills and
      lignocellulose-based biorefineries, for combined production of liquid biofuel and
      biocatalysts was investigated. Without pretreatment, fiber sludge was hydrolyzed
      enzymatically to monosaccharides, mainly glucose and xylose. In the first of two
      sequential fermentation steps, the fiber sludge hydrolysate was fermented to
      cellulosic ethanol with the yeast Saccharomyces cerevisiae. Although the final
      ethanol yields were similar, the ethanol productivity after 9.5 h was 3.3 g/l/h
      for the fiber sludge hydrolysate compared with only 2.2 g/l/h for a reference
      fermentation with similar sugar content. In the second fermentation step, the
      spent fiber sludge hydrolysate (the stillage obtained after distillation) was
      used as growth medium for recombinant Aspergillus niger expressing the xylanase
      encoding Trichoderma reesei (Hypocrea jecorina) xyn2 gene. The xylanase activity
      obtained with the spent fiber sludge hydrolysate (8,500 nkat/ml) was higher than
      that obtained in a standard medium with similar monosaccharide content (1,400
      nkat/ml). Analyses based on deglycosylation with N-glycosidase F suggest that the
      main part of the recombinant xylanase was unglycosylated and had molecular mass
      of 20.7 kDa, while a minor part had N-linked glycosylation and molecular mass of
      23.6 kDa. Chemical analyses of the growth medium showed that important carbon
      sources in the spent fiber sludge hydrolysate included xylose, small aliphatic
      acids, and oligosaccharides. The results show the potential of converting waste
      fiber sludge to liquid biofuel and enzymes as coproducts in lignocellulose-based
      biorefineries.

PMID- 20824488
TI  - Human pathogens, nosocomial infections, heat-sensitive textile implants, and an
      innovative approach to deal with them.
AB  - Implantable polymers, as used for biomedical applications, inherently have to be
      sterile. Nonetheless, most implants, particularly those comprised of biomaterials
      developed in recent years for tissue engineering, are heat sensitive. Therefore,
      use of hazardous (radio)chemicals--due to lack of alternative methods--is still
      state of the art for sterilization processes. The drawbacks of these techniques,
      both drastic and well known, lead to the demand for an alternative sterilization
      method, which is equally obvious and urgent. High-pressure fluid treatment is a
      low-temperature technique that is already in use for pasteurization of liquid
      food products. This paper explores inactivation of vegetative microorganisms,
      spores, and endotoxins adherent to solid surfaces using compressed CO(2).
      Pressures ranging from 50 to 100 bar and temperatures from 25  degrees C to 50 
      degrees C were explored to investigate liquid, gaseous or supercritical state.
      Analysis of variance (ANOVA) and statistical modeling were used to identify the
      optimum parameter settings for inactivation of pathogenic bacteria and fungi
      (Candida albicans, Staphylococcus aureus). The addition of small amounts of ozone
      ensures inactivation of persistent spores (Bacillus stearothermophilus, B.
      subtilis) up to 10(6) cfu/ml, while endotoxins remain in practically unchanged
      concentration on the polymer surface. We then discuss environmental issues of the
      process and inactivation mechanisms. The replacement of conventional chemicals
      with nonpersistent ones resolves organizational and safety-related issues and
      protects natural resources as well as handling staff. The pressurized-fluid-based
      method exhibits mild treatment parameters, thus protecting sensitive textures.
      Finally, an outlook on possible applications of this innovative technique is
      presented.

PMID- 20824489
TI  - Production of L-lactic acid by Rhizopus oryzae using semicontinuous fermentation
      in bioreactor.
AB  - Semicontinuous fermentation using pellets of Rhizopus oryzae has been recognized
      as a promising technology for L-lactic acid production. In this work,
      semicontinuous fermentation of R. oryzae AS 3.819 for L-lactic acid production
      has been developed with high L-lactic acid yield and volumetric productivity. The
      effects of factors such as inoculations, CaCO3 addition time, and temperature on
      L-lactic acid yield and R. oryzae morphology were researched in detail. The
      results showed that optimal fermentation conditions for the first cycle were:
      inoculation with 4% spore suspension, CaCO3 added to the culture medium at the
      beginning of culture, and culture temperature of 32-34  degrees C. In orthogonal
      experiments, high L-lactic acid yield was achieved when the feeding medium was
      (g/l): glucose, 100; (NH4)2SO4, 2; KH2PO4, 0.1; ZnSO4.7H2O, 0.33; MgSO4.7H2O,
      0.15; CaCO3, 50. Twenty cycles of semicontinuous fermentation were carried out in
      flask culture. L: -lactic acid yield was 78.75% for the first cycle and 80-90%
      for the repeated cycles; the activities of lactate dehydrogenases (LDH) were 7.2
      9.2 U/mg; fermentation was completed in 24 h for each repeated cycle. In a 7-l
      magnetically stirred fermentor, semicontinuous fermentation lasted for 25 cycles
      using pellets of R. oryzae AS 3.819 under the optimal conditions determined from
      flask cultures. The final L-lactic acid concentration (LLAC) reached 103.7 g/l,
      and the volumetric productivity was 2.16 g/(l.h) for the first cycle; in the
      following 19 repeated cycles, the final LLAC reached 81-95 g/l, and the
      volumetric productivities were 3.40-3.85 g/(l.h).

PMID- 20824490
TI  - Silencing USP22 by asymmetric structure of interfering RNA inhibits proliferation
      and induces cell cycle arrest in bladder cancer cells.
AB  - The ubiquitin specific peptidase 22 (USP22) is a positive regulator of the growth
      of tumors. However, little is known about the impact of USP22 knockdown on the
      growth of human bladder cells. In the present study, we designed a series of
      asymmetric interfering RNAs (aiRNAs) and compared the efficacy of aiRNA and
      conventional symmetric interfering RNA (siRNA) in the silencing of USP22
      expression and the growth of human bladder EJ cells in vitro and in vivo. In
      comparison with transfection with the USP22-specific siRNA, transfection with
      15/21 aiRNA was more potent in down-regulating the USP22 expression and
      inhibiting EJ cell proliferation in vitro. Furthermore, transfection with 15/21
      aiRNA induced higher frequency of EJ cells arrested at the G0/G1 phases, but did
      not trigger EJ cell apoptosis. Moreover, transfection with either the siRNA or
      15/21 aiRNA up-regulated the expression of p53 and p21, but down-regulated the
      expression of cyclin E and Mdm2 in EJ cells. The up-regulated p53 expression
      induced by the specific siRNA or aiRNA was abrogated by induction of Mdm2 over
      expression. In addition, treatment with the specific siRNA or aiRNA inhibited the
      growth of implanted human bladder tumors in mice and the aiRNA had more potent
      anti-tumor activity in vivo. Therefore, our data suggest that knockdown of USP22
      expression by the aiRNA may down-regulate the expression of Mdm2 and cyclin E,
      resulting in the up-regulated expression of p53 and p21 and leading to cell
      cycling arrest and inhibition of human bladder EJ cell proliferation. Our
      findings indicate that the USP22-specific aiRNA may be a novel approach for the
      intervention of human bladder tumors.

PMID- 20824491
TI  - Editorial: The mammary stroma in normal development and function.
AB  - The mammary gland can no longer be simply viewed as an organ composed of
      epithelial cells within a passive stromal microenvironment. Many lines of
      evidence have evolved to reinforce the notion that mammary epithelial cell
      growth, differentiation, lactation and progression to cancer involves
      bidirectional interactions between the epithelial population and its surrounding
      stroma. Within this stroma are numerous systems that are all capable of
      modulating epithelial function. In this context, the mammary stroma is not simply
      a depot of adipose tissue in which mammary epithelial cells undertake a unique
      growth and differentiation process, although adipocytes can impart numerous
      modulatory signals to epithelial cells, and vice versa. Rather, the stromal
      environment constitutes and supports a critical vasculature that supplies
      nutrients and endocrine cues, a lymphatic system that not only removes
      metabolites but also provides an intimate interface with the immune system, and
      an extracellular matrix scaffold in which epithelial cells grow, differentiate
      and regress. Ultimately all of these components play a critical role in directing
      the epithelial phenotype during normal mammary gland growth and function. An
      increasing appreciation for these different systems demands a view of mammary
      epithelial cells in a much different light, and further necessitates the
      development of model systems that incorporate and integrate increasing
      complexity.

PMID- 20824493
TI  - Kiddie-SADS reveals high rates of DSM-IV disorders in children and adolescents
      with autism spectrum disorders.
AB  - Prevalence of current comorbid DSM-IV disorders was assessed in a special school
      population of children and adolescents with ASD (N = 71, age 6.0-17.9 years),
      representing all cognitive levels and main ASD subgroups. Symptoms were assessed
      through parent interview and association to child characteristics was explored.
      Seventy-two percent was diagnosed with at least one comorbid disorder. Anxiety
      disorders (41%) and attention deficit/hyperactivity disorder (31%) were most
      prevalent. Obsessive-compulsive disorder was more common in older children, and
      oppositional defiant disorder/conduct disorder more prevalent in pervasive
      developmental disorder, not otherwise specified. Our results show high rates of
      comorbid DSM-IV disorders and underscore the importance of such evaluation in
      children ASD. However, diagnostic challenges are present and future research on
      the diagnostic validity of comorbid psychiatric disorders is needed.

PMID- 20824492
TI  - The normal microenvironment directs mammary gland development.
AB  - Normal development of the mammary gland is a multidimensional process that is
      controlled in part by its mammary microenvironment. The mammary microenvironment
      is a defined location that encompasses mammary somatic stem cells, neighboring
      signaling cells, the basement membrane and extracellular matrix, mammary
      fibroblasts as well as the intercellular signals produced and received by these
      cells. These dynamic signals take numerous forms including growth factors,
      steroids, cell-cell or cell-basement membrane physical interactions. Cellular
      growth and differentiation of the mammary gland throughout the developmental
      stages are regulated by changes in these signals and interactions. The purpose of
      this review is to summarize current information and research regarding the role
      of the mammary microenvironment during normal glandular development.

PMID- 20824494
TI  - Reversal of rotenone-induced dysfunction of astrocytic connexin43 by opening
      mitochondrial ATP-sensitive potassium channels.
AB  - Growing evidence suggests that the astrocytic gap junctions (GJs), mainly formed
      by connexin 43 (Cx43), play an important role in physiological maintenance and
      various central nervous system (CNS) pathological conditions. However, little is
      known about the role of Cx43 in Parkinson's disease (PD). In this article, we
      report that rotenone, a classic neurotoxin for PD, could inhibit expression of
      astrocytic Cx43 and gap junction permeability. ATP-sensitive potassium (K(ATP))
      channel openers, iptakalim (IPT) and diazoxide (DZ), exerted protective effect on
      rotenone-induced dysfunction of Cx43 and astrocyte apoptosis, which was reversed
      by selective mitochondrial K(ATP) (mitoK(ATP)) channel blocker 5-hydroxydecanoate
      (5-HD). Taken together, our findings reveal that rotenone-induced dysfunction of
      astrocytic Cx43 may be involved in the pathology of PD. Moreover, opening
      mitoK(ATP) channels in astrocytes can reverse rotenone-induced dysfunction of
      astrocytic Cx43 and therefore protect against toxicity of rotenone on astrocytes.

PMID- 20824496
TI  - Beneficial effects of follistatin in hepatic ischemia-reperfusion injuries in
      rats.
AB  - BACKGROUND: Ischemia-reperfusion injury has been demonstrated in a variety of
      clinical settings. The morbidity associated with liver transplantation and major
      hepatic resections is partly a result of ischemia-reperfusion injury.
      Follistatin, an activin-binding protein, binds to activins and subsequently
      blocks their action. It was reported that blockade of the action of activin with
      administration of follistatin accelerates recovery from ischemia renal injury.
      This study was conducted to investigate the involvement of the activin
      follistatin system in hepatic ischemia-reperfusion injury. METHODS: Total hepatic
      ischemia for 30 min was performed followed by reperfusion in a rat model. Rats
      were divided into two groups: a follistatin group and a control group.
      Follistatin (1 MUg/body), which is an activin-binding protein, was administered
      at the time of reperfusion. RESULTS: Though 80% of animals survived in the
      follistatin group, four of five animals died in the control group within 3 days
      after reperfusion (p<0.05). AST was significantly lower at 3 h after reperfusion
      in the follistatin group (p<0.05). LDH was also lower at 6 h after reperfusion in
      the follistatin group (p<0.05). Follistatin inhibited the mRNA expression of the
      betaA subunit of activin. Moreover, the expression of IL-6, which is an
      inflammatory cytokine, was suppressed at 6 h after reperfusion in the follistatin
      group (p<0.05). CONCLUSIONS: The present study demonstrated that treatment with
      follistatin reduced the expression of IL-6 and activin resulting in beneficial
      support for hepatic ischemia-reperfusion injuries.

PMID- 20824497
TI  - Can an immunohistochemistry method differentiate intestinal tuberculosis from
      Crohn's disease in biopsy specimens?
AB  - BACKGROUND: It is sometimes difficult to diagnose whether a patient has
      intestinal tuberculosis or Crohn's disease because both have similar clinical,
      pathologic, and endoscopic features. However, their therapies are completely
      different and a mistake in diagnosis can result with deterioration. Many
      laboratory methods for the diagnosis of tuberculosis require considerable time to
      receive a diagnostic result. We wanted to evaluate whether an immunohistochemical
      tuberculosis staining method can be helpful for faster differentiation of biopsy
      materials. METHODS: We used formalin-fixed paraffin-embedded histologically
      diagnosed small intestine (n=1), colon (n=7), skin (n=8), lung (n=5), lymph node
      (n=24) tuberculosis and Crohn's disease (n = 28) biopsy materials only with
      granulomas. Demographic characteristics like age and gender were also obtained.
      Pathology specimens were stained immunohistochemically with an antibody to VP
      M660, targeting the 38-kDa antigen of Mycobacterium tuberculosis. RESULTS: In the
      M. tuberculosis group, 33/45 of patients have positive immunohistochemistry (IHC)
      staining (73% sensitivity, 93% specificity), whereas only two of 28 patients have
      positive staining in the Crohn's group (p<0.001). The positive staining with IHC
      was detected as 85.7, 75, 75, and 60% in colon, lymph node, skin, and lung
      granulomas, respectively, in M. tuberculosis patients. CONCLUSIONS:
      Immunohistochemical staining of biopsy specimens with anti-VP-M660 seems to be a
      simple and fast technique with 73% sensitivity and 93% specificity for
      establishing an earlier differentiation of M. tuberculosis from Crohn's disease.

PMID- 20824498
TI  - Impact of obesity and leptin on protein expression profiles in mouse colon.
AB  - BACKGROUND: Elevated leptin levels in obesity are associated with increased risk
      of colon pathology, implicating leptin signaling in colon disease. However,
      leptin-regulated processes in the colon are currently uncharacterized.
      Previously, we demonstrated that leptin receptors are expressed on colon
      epithelium and that increased adiposity and elevated plasma leptin in rats are
      associated with perturbed metabolism in colon tissue. Thus, we hypothesize that
      obesity disrupts expression of proteins regulated by leptin in the colon.
      METHODS: A proteomic analysis was conducted to investigate firstly, differences
      in the colon of mice lacking leptin and leptin signaling (ob/ob and db/db,
      respectively) by comparing protein expression profiles with wild-type mice.
      Secondly, responses to leptin challenge in wild-type mice and ob/ob mice were
      compared to identify leptin-regulated proteins and associated cellular processes.
      RESULTS: Forty proteins were identified with significantly altered expression
      patterns associated with differences in leptin status in comparisons between all
      groups of mice. These proteins are associated with calcium binding, cell cycle,
      cell proliferation, electron transport chain, energy metabolism, protein folding
      and transport, redox regulation, structural proteins, and proteins involved in
      transport and regulation of mucus production. CONCLUSIONS: This study provides
      evidence that obesity and leptin significantly alter protein profiles of a number
      of proteins linked to cellular processes in colon tissues that may be linked to
      the increased risk of colon pathology associated with obesity.

PMID- 20824500
TI  - Metal stents and biliary obstruction secondary to lymphoma: a tale of caution.

PMID- 20824499
TI  - Pioglitazone: a promising therapeutic tool in sodium taurocholate-induced severe
      acute pancreatitis.
AB  - BACKGROUND: Studies suggest that peroxisome proliferator-activated receptor
      gamma(PPARgamma) ligands may represent a therapeutic option in acute
      pancreatitis, yet most of them have been prophylactic administrated. AIMS: To
      evaluate the therapeutic effect of pioglitazone in rats with severe acute
      pancreatitis induced by sodium taurocholate. METHODS: Severe acute pancreatitis
      (SAP) was induced in male Sprague-Dawley rats by the retrograde injection of 5%
      sodium taurocholate into the pancreatic duct. After SAP was induced, pioglitazone
      was injected intraperitoneally and its role on the severity of inflammatory
      response and pancreatic injury was investigated. Amylase activity, inflammatory
      cytokines production, pathological changes of pancreas, PPARgamma mRNA
      expression, and the survival rate were examined. RESULTS: Treatment with
      pioglitazone decreased the level of amylase activity, proinflammatory factors IL
      6 and TNF-alpha, ameliorated pancreatic histological score, and upregulated the
      expression of PPARgamma mRNA. The survival rate in the early stage of severe
      acute pancreatitis was also improved. CONCLUSIONS: Pioglitazone can be used as a
      therapeutic drug and relieve the damages caused by SAP, which suggests PPARgamma
      ligand-pioglitazone offers a potent approach for the treatment of severe acute
      pancreatitis.

PMID- 20824501
TI  - Prospective evaluation of quality of life in patients with Zollinger-Ellison
      syndrome.
AB  - BACKGROUND: Zollinger-Ellison syndrome (ZES) is associated with complicated ulcer
      disease of the upper gastrointestinal tract. While management of ZES has
      dramatically improved with proton pump inhibitor therapy, quality of life in
      medically treated patients has not been evaluated. METHODS: Over a 3-year period,
      52 patients with ZES were prospectively evaluated at 6-month intervals with upper
      endoscopy and gastric acid analysis to evaluate the efficacy of current drug
      therapy and completion of SF36v2 forms. At each 6-month visit, patients'
      medication and problem lists were reviewed, comorbidities assessed, and any
      gastrointestinal symptoms recorded. Co-morbidity was represented as a simple
      illness count for the main analysis. The chronic disease score and the Charlson
      index were used for sensitivity analyses. RESULTS: The unadjusted norm-based
      estimate of mental component score (MCS) for 52 patients with ZES (mean age 58,
      65% male) was 49.8 (95% CI 46.4, 53.1). The unadjusted estimate of the physical
      component score (PCS) was 42.3 (95% CI 38.9, 45.7). As the number of illnesses or
      number of medications increased, there was a monotonic decrease in PCS scores.
      With multivariable adjustment, the coefficient for number of medications became
      non-significant. An increase in each of the co-morbidity indexes was associated
      with a decrease in PCS. Results did not vary by representation of co-morbidity.
      MCS was not significantly different from the general population. CONCLUSIONS:
      Patients with medically managed ZES have norm-based estimates of the mental
      component scores as measured by the SF-36v2 that approximate normal values, while
      the physical component scores were decreased with this reduction largely
      explained by co-morbid illness.

PMID- 20824502
TI  - The expression of both peroxisome proliferator-activated receptor delta and
      cyclooxygenase-2 in tissues is associated with poor prognosis in colorectal
      cancer patients.
AB  - BACKGROUND: The role of peroxisome proliferator-activated receptor delta (PPAR
      delta) in the development and progression of colorectal cancer (CRC) remains
      controversial. AIMS: We investigated the impact of PPAR delta expression in
      tissues on liver metastasis of CRC. METHODS: We analyzed samples of primary CRC
      and matched normal adjacent tissues from 52 patients for the expression of PPAR
      delta, cyclooxygenase (COX)-2, vascular endothelial growth factor (VEGF)-A, and
      CXC chemokine receptor 4 (CXCR4). Correlations of the molecules expressions with
      clinical characteristics and prognosis of patients were studied. RESULTS: The
      number of patients positive for PPAR delta, COX-2, CXCR4, and VEGF-A was 25, 33,
      18, and 19, respectively. Among the PPAR delta (+)/COX-2 (+), PPAR delta (-)/COX
      2 (+), PPAR delta (+)/COX-2 (-), and PPAR delta (-)/COX-2 (-) patient groups,
      PPAR delta (+)/COX-2 (+) patients had the highest incidence of liver metastasis
      (p<0.01). PPAR delta (+)/COX-2 (+) expression was a significant independent
      prognostic factor (HR=7.108, 95% CI 1.231-41.029, p=0.0283) by Cox proportional
      analysis. PPAR delta (+)/COX-2 (+) patients had the highest positivity for CXCR4
      or VEGF-A in tissues (p<0.01). Among the patients in the CXCR4 (+)/VEGF-A (+),
      CXCR4 (+)/VEGF-A (-), CXCR4 (-)/VEGF-A (+), and CXCR4 (-)/VEGF-A (-) groups,
      CXCR4 (+)/VEGF-A (+) patients had the highest incidence of liver metastasis
      (p<0.01). CONCLUSIONS: The expression of both PPAR delta and COX-2 in tissues may
      lead to liver metastasis and consequent poor prognosis in CRC patients.

PMID- 20824503
TI  - Sedation and polyp detection.

PMID- 20824504
TI  - Sustained renal response to mycophenolate mofetil and CNI taper promotes survival
      in liver transplant patients with CNI-related renal dysfunction.
AB  - AIM: The aim of this trial was to evaluate the impact of conversion from a
      calcineurin-inhibitor (CNI)-based immunosuppressive regimen to mycophenolate
      mofetil (MMF) and reduced-dose CNI on long-term renal function and survival in a
      series of 63 liver transplant patients with CNI-induced renal dysfunction.
      METHODS: CNI dosage was significantly tapered after introduction of 2,000 mg MMF
      per day. Renal function was assessed by determination of serum creatinine levels
      and calculated creatinine clearance (CCl). The impact of relevant clinical
      parameters on renal function and survival post-conversion was analyzed by
      univariate and multivariate analysis. RESULTS: At 60 months post-conversion, mean
      creatinine level had significantly declined from 197.2+/-58.3 MUmol/l at baseline
      to 160.0+/-76.5 MUmol/l, and mean CCl has significantly increased from 38.4+/
      13.4 ml/min at baseline to 47.9+/-21.1 ml/min (p<0.001), respectively. Forty-six
      patients (73.1%) demonstrated sustained renal response to modified
      immunosuppression. Full-dose MMF medication (p=0.006) and the early conversion
      (p=0.02) were identified as independent predictors of persistent renal function
      improvement. Sustained renal response to MMF plus reduced-dose CNI was identified
      as the most relevant independent promoter of long-term survival (hazard ratio
      6.9). Five-year survival rate post-conversion was 93.9% in renal responders and
      64.3% in renal non-responders (log rank<0.001). CONCLUSIONS: Sustained renal
      response to MMF and CNI dose reduction promotes long-term survival in liver
      transplant patients with CNI-induced renal dysfunction.

PMID- 20824505
TI  - Renin-angiotensin system associated with risk of upper GI mucosal injury induced
      by low dose aspirin: renin angiotensin system genes' polymorphism.
AB  - BACKGROUND: We have previously shown that co-treatment of angiotensin type 1
      receptor (AT1R) blocker (ARB) or angiotensin converting enzyme (ACE) inhibitor
      seem to reduce peptic ulcer among patients taking low dose aspirin. It is
      reported that a series of renin-angiotensin system (RAS) gene polymorphisms
      significantly influence the rate of the gene transcription. AIM: The aim of this
      study was to examine the genotypes of RAS genes related to the risk of peptic
      ulcer and ulcer bleeding among patients taking low dose aspirin. METHODS:
      Patients taking 100 mg of aspirin who were planning to undergo endoscopy for
      surveillance or who had history of recent upper GI ulcer bleeding were included.
      ACE (Ins/Del), angiotensinogen (AGT; G-217A, A-20C, A-6G, T174 M, M235T), and
      AT1R (T-713G, C-521T, A1166C) genotypes were determined by PCR or PCR-RFLP.
      RESULTS: Four hundred twenty-five patients were enrolled including 68 patients
      with peptic ulcer and 20 patients with ulcer bleeding. Co-treatment of ARB was
      significantly associated with peptic ulcer and ulcer bleeding. AGT-20 CC
      (adjusted OR 4.94, 95% CI 1.21-20.2) was significantly associated with ulcer
      bleeding. The CC genotype of AT1R-521 was significantly associated with peptic
      ulcer only in the subgroup taking neither ACE inhibitor nor ARB. CONCLUSIONS: Co
      treatment of ARB reduces peptic ulcer and bleeding among patients taking low dose
      aspirin. RAS may play an important role in the development of upper GI mucosal
      injury induced by low dose aspirin.

PMID- 20824506
TI  - Lafutidine, a protective H2 receptor antagonist, enhances mucosal defense in rat
      esophagus.
AB  - BACKGROUND: Luminal acid or CO2 induces a hyperemic response in the esophagus,
      via activation of acid sensors on capsaicin-sensitive afferent nerves (CSAN).
      Since disruption of the hyperemic response to luminal CO2 acidifies the
      interstitium of the esophageal mucosa, the hyperemic response may maintain
      interstitial pH (pH(int)). We hypothesized that acid-related hyperemia maintains
      pH(int), preventing acid-induced injury in the esophageal mucosa. METHODS: We
      examined the effects of capsaicin (Cap) or lafutidine (Laf), a mucosal protective
      H2 antagonist, on the regulation of pH(int) and blood flow in rat esophagus using
      ratiometric microimaging and laser-Doppler measurements of the lower esophageal
      mucosa of living rats. The esophagus was topically superfused with pH 7.0 buffer,
      or a pH 1.0 or pH 1.0 + pepsin (1 mg/ml) solution with or without Laf. RESULTS:
      Cap (30 or 100 uM) or Laf (0.1 or 1 mM) dose-dependently increased blood flow,
      accompanied by increased pH(int). The pH 1.0 solution increased blood flow
      without pH(int) change, whereas Laf (1 mM) increased blood flow and pH(int)
      during acid exposure. The effects of Laf were abolished by ablation of CSAN.
      Perfusion of the acidified pepsin solution gradually decreased pH(int), inhibited
      by Laf perfusion. CONCLUSIONS: Activation of CSAN by Laf with or without acid,
      accompanied by hyperemia, increased pH(int), preventing acidified pepsin-induced
      interstitial acidification. Stimulation of the capsaicin pathway with compounds
      such as Laf enhances mucosal protection from acid-related injury in the upper
      gastrointestinal tract.

PMID- 20824507
TI  - Cardiac magnetic resonance determinants of functional mitral regurgitation in
      ischemic and non ischemic left ventricular dysfunction.
AB  - Functional mitral regurgitation (FMR) is frequent in left ventricular (LV)
      dilatation/dysfunction. Echocardiographic predictors of FMR are known. However,
      cardiac magnetic resonance (CMR) predictors of FMR have not been fully addressed.
      The aim of the study was to evaluate CMR mitral valve (MV) parameters associated
      with FMR in ischemic and non ischemic LV dysfunction. 80 patients with LV
      ejection fraction below 45% and/or left ventricular dilatation of ischemic and
      non ischemic etiology were included. Cine-MR images (steady state free
      precession) were acquired in a short-axis and 4 chambers views where MV
      evaluation was performed. Delayed enhancement was performed as well. Significant
      FMR was established as more than mild MR according to the echocardiographic
      report. Mean age was 59 years, males 79%. FMR was detected in 20 patients (25%)
      Significant differences were noted in LV functional parameters and in most MV
      parameters according to the presence of significant FMR. However, differences
      were noted between ischemic and non ischemic groups. In the first, differences in
      most MV parameters remained significant while in the non ischemic, only systolic
      and diastolic interpapillary muscle distance (1.60 vs. 2.19 cm, P = 0.001; 2. 51
      vs. 3.04, P = 0.008) were predictors of FMR. FMR is associated with a more severe
      LV dilatation/dysfunction in the overall population. CMR MV parameters are
      associated with the presence of significant FMR and are different between
      ischemic and non ischemic patients. CMR evaluation of these patients may help in
      risk stratification as well as in surgical candidate selection.

PMID- 20824508
TI  - Assessing p-glycoprotein (Pgp) activity in vivo utilizing 68Ga-Schiff base
      complexes.
AB  - PURPOSE: The p-glycoprotein (Pgp) is the most prominent member of active drug
      transporters leading to a multidrug-resistant phenotype. For identification of
      tumors functionally overexpressing Pgp in vivo, non-invasive imaging techniques
      are needed. PROCEDURES: Six Schiff base compounds were synthesized and labeled
      with (68)Ge/(68)Ga generator-derived (68)Ga. The compounds were studied in vitro
      in Pgp-positive tumor cells. The property of being a Pgp substrate was tested by
      comparison of the tracers uptake in R-3327 Dunning prostate carcinoma AT1 cells
      in presence and absence of the Pgp-inhibitor verapamil. In vivo investigations
      were performed with tumor-bearing rats imaged with micro-positron emission
      tomography. RESULTS: All ligands were labeled with (68)Ga in yields of >92%
      beside one (~55%). The tracers showed different accumulation within the cells in
      vitro (4-60%). In blocking experiments, the ratio (blocked to unblocked) varied
      from 1.8 to 1.0. For in vivo experiments, (68)Ga-ENBDMPI and (68)Ga-MFL6.MZ were
      selected. The tumors showed specific uptake of the tracer. Direct intratumoral
      injection of verapamil increased the tracer concentration by ~25% reflecting the
      functional Pgp activity. CONCLUSIONS: Two (68)Ga-labeled ligands appear to be
      valuable for imaging non-invasively the intratumoral Pgp activity. On a long
      term, patients with multidrug-resistant tumors pre-therapeutically may be
      identified prior to treatment.

PMID- 20824509
TI  - Pancreatic beta cell mass PET imaging and quantification with [11C]DTBZ and
      [18F]FP-(+)-DTBZ in rodent models of diabetes.
AB  - PURPOSE: The aim of this study is to compare the utility of two positron emission
      tomography (PET) imaging ligands ((+)-[(11)C]dihydrotetrabenazine ([(11)C]DTBZ)
      and the fluoropropyl analog ([(18)F]FP-(+)-DTBZ)) that target islet beta-cell
      vesicular monoamine transporter type II to measure pancreatic beta-cell mass
      (BCM). PROCEDURES: [(11)C]DTBZ or [(18)F]FP-(+)-DTBZ was injected, and serial PET
      images were acquired in rat models of diabetes (streptozotocin-treated and Zucker
      diabetic fatty) and beta-cell compensation (Zucker fatty). Radiotracer
      standardized uptake values (SUV) were correlated to pancreas insulin content
      measured biochemically and histomorphometrically. RESULTS: On a group level, a
      positive correlation of [(11)C]DTBZ pancreatic SUV with pancreas insulin content
      and BCM was observed. In the STZ diabetic model, both [(18)F]FP-(+)-DTBZ and
      [(11)C]DTBZ correlated positively with BCM, although only ~25% of uptake could be
      attributed to beta-cell uptake. [(18)F]FP-(+)-DTBZ displacement studies indicate
      that there is a substantial fraction of specific binding that is not to
      pancreatic islet beta cells. CONCLUSIONS: PET imaging with [(18)F]FP-(+)-DTBZ
      provides a noninvasive means to quantify insulin-positive BCM and may prove
      valuable as a diagnostic tool in assessing treatments to maintain or restore BCM.

PMID- 20824510
TI  - Articulated whole-body atlases for small animal image analysis: construction and
      applications.
AB  - PURPOSE: Using three publicly available small-animal atlases (Sprague-Dawley rat,
      MOBY, and Digimouse), we built three articulated atlases and present several
      applications in the scope of molecular imaging. PROCEDURES: Major bones/bone
      groups were manually segmented for each atlas skeleton. Then, a kinematic model
      for each atlas was built: each joint position was identified and the
      corresponding degrees of freedom were specified. RESULTS: The articulated atlases
      enable automated registration into a common coordinate frame of multimodal small
      animal imaging data. This eliminates the postural variability (e.g., of the head,
      back, and front limbs) that occurs in different time steps and due to modality
      differences and nonstandardized acquisition protocols. CONCLUSIONS: The
      articulated atlas proves to be a useful tool for multimodality image combination,
      follow-up studies, and image processing in the scope of molecular imaging. The
      proposed models were made publicly available.

PMID- 20824511
TI  - Laparoscopic reconversion of Roux-en-Y gastric bypass to original anatomy:
      technique and preliminary outcomes.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (RYGB) is one of the most
      common bariatric procedures performed. Dumping syndrome, intolerance to RYGB
      induced restriction, and weight loss issues are possible problems bariatric
      surgeons are confronted with. This study reports the feasibility, safety, and
      outcomes of laparoscopic reconversion of RYGB to original anatomy (OA) as
      treatment of these complications. METHODS: Between January 2005 and April 2008,
      eight patients benefited from laparoscopic reconversion of RYGB to OA. Reason was
      dumping syndrome without postprandial hypoglycemia (three), intolerance to RYGB
      induced restriction (three), too much (one) and too little weight loss (one).
      Mean weight and body mass index (BMI) at RYGB were 104.7+/-19.3 kg and 38.7+/-6
      kg/m(2), respectively. Four patients suffered of obesity co-morbidities. Mean
      time between RYGB and reconversion was 21+/-18.8 months. Mean weight, BMI, and %
      excess weight loss at reconversion was 66.8+/-21.7 kg, 20.1+/-7 kg/m(2), and
      23.7+/-55%, respectively. The procedure involved dismantling both
      gastrojejunostomy and jejunojejunostomy, reanastomosing gastric pouch to gastric
      remnant, and proximal alimentary limb end to distal biliary limb end. RESULTS:
      Mean operative time was 132.2+/-29.5 min. There were no conversions to open
      surgery and no early complications. Gastrogastrostomy was performed manually
      (four) and by linear stapler (four), and jejunojejunostomy by linear stapler
      (eight). Mean hospital stay was 7.7+/-3.5 days. After a mean follow-up of 18.3+/
      9.2 months, two patients continued to further lose weight, two patients
      maintained the same weight, and four patients presented weight regain.
      Gastroesophageal reflux disease appeared in three patients. CONCLUSIONS:
      Laparoscopic reconversion of RYGB to OA is feasible and safe. Dumping syndrome
      and intolerance to RYGB-induced restriction are resolved. The anatomy remains one
      of the aspects besides nutritional and psychological factors in cases of
      reconversion for weight issues.

PMID- 20824513
TI  - Controlled release matrix tablets of olanzapine: influence of polymers on the in
      vitro release and bioavailability.
AB  - Controlled-release (CR) tablet formulation of olanzapine was developed using a
      binary mixture of Methocel(r) K100 LV-CR and Ethocel(r) standard 7FP premium by
      the dry granulation slugging method. Drug release kinetics of CR tablet
      formulations F1, F2, and F3, each one suitably compressed for 9-, 12-, and 15-kg
      hardness, were determined in a dissolution media of 0.1 N HCl (pH 1.5) and
      phosphate buffer (pH 6.8) using type II dissolution apparatus with paddles run at
      50 rpm. Ethocel(r) was found to be distinctly controlling drug release, whereas
      the hardness of tablets and pH of the dissolution media did not significantly
      affect release kinetics. The CR test tablets containing 30% Methocel(r) and 60%
      Ethocel(r) (F3) with 12-kg hardness exhibited pH-independent zero-order release
      kinetics for 24 h. In vivo performance of the CR test tablet and conventional
      reference tablet were determined in rabbit serum using high-performance liquid
      chromatography coupled with electrochemical detector. Bioavailability parameters
      including C(max), T(max), and AUC(0-48 h) of both tablets were compared. The CR
      test tablets produced optimized C(max) and extended T(max) (P < 0.05). A good
      correlation of drug absorption in vivo and drug release in vitro (R(2) = 0.9082)
      was observed. Relative bioavailability of the test tablet was calculated as 94%.
      The manufacturing process employed was reproducible and the CR test tablets were
      stable for 6 months at 40 +/- 2 degrees C/75 +/- 5% relative humidity. It was
      concluded that the CR test tablet formulation successfully developed may improve
      tolerability and patient adherence by reducing adverse effects.

PMID- 20824512
TI  - Seeing beyond the average cell: branching process models of cell proliferation,
      differentiation, and death during mouse brain development.
AB  - We develop a family of branching process models to study cerebral cortical
      development at the level of individual neural stem and progenitor cells (NS/PCs)
      and the neurons they produce. Population-level data about "the average NS/PC" is
      incorporated as constraints for exploring (i) heterogeneity in the proliferative
      neural cell types and (ii) variability in daughter cell fate decision making.
      Preliminary studies demonstrate this variability, generate testable hypotheses
      about heterogeneity, and motivate new experiments moving forward.

PMID- 20824514
TI  - A preformulation study of a new medicine for Chagas disease treatment:
      physicochemical characterization, thermal stability, and compatibility of
      benznidazole.
AB  - This work aimed the studies of physicochemical characterization, thermal
      stability, and compatibility of benznidazole (BNZ) drug by spectroscopy (NMR,
      IR), thermoanalytical (differential thermal analysis, differential scanning
      calorimetry, and thermogravimetry), and chromatographic (HPLC) techniques, beyond
      the analytical tools of Van't Hoff equation and Ozawa model. The compatibility
      study was conducted by binary mixtures (1:1, w/w) of the drug with
      microcrystalline cellulose 102 and 250, anhydrous lactose, and sodium starch
      glycolate. The physicochemical characterization confirmed data reported in
      scientific literature, guaranteeing authenticity of the analyzed raw material.
      The drug melts at 191.68 degrees C (?H, 119.71 J g(-1)), characteristic of a non
      polymorphic raw material, and a main stage decomposition at 233.76-319.35 degrees
      C (?m, 43.32%) occurred, ending the study with almost all mass volatilized. The
      quantification of drug purity demonstrated a correlation of 99.63% between the
      data obtained by chromatographic (99.20%) and thermoanalytical technique
      (99.56%). The Arrhenius equation and Ozawa model showed a zero-order kinetic
      behavior for the drug decomposition, and a calculated provisional validity time
      was 2.37 years at 25 degrees C. The compatibility study evidenced two possible
      chemical incompatibilities between BNZ and the tested excipients, both associated
      by the authors to the reaction of the BNZ's amine and a polymer carbohydrate's
      carbonile, being maillard reactions. The BNZ reaction with anhydrous lactose is
      more pronounced than with the sodium starch glycolate because the lactose has
      more free hydroxyl groups to undergo reduction by the drug. In this sense, this
      work guides the development of a new solid pharmaceutical product for Chagas
      disease treatment, with defined quality control parameters and physicochemical
      stability.

PMID- 20824515
TI  - Development and evaluation of emulsions from Carapa guianensis (Andiroba) oil.
AB  - Carapa guianensis, a popular medicinal plant known as "Andiroba" in Brazil, has
      been used in traditional medicine as an insect repellent and anti-inflammatory
      product. Additionally, this seed oil has been reported in the literature as a
      repellent against Aedes aegypti. The aim of this work is to report on the
      emulsification of vegetable oils such as "Andiroba" oil by using a blend of
      nonionic surfactants (Span 80(r) and Tween 20(r)), using the critical hydrophilic
      lipophilic balance (HLB) and pseudo-ternary diagram as tools to evaluate the
      system's stability. The emulsions were prepared by the inverse phase method.
      Several formulations were made according to a HLB spreadsheet design (from 4.3 to
      16.7), and the products were stored at 25 degrees C and 4 degrees C. The emulsion
      stabilities were tested both long- and short-term, and the more stable one was
      used for the pseudo-ternary diagram study. The emulsions were successfully
      obtained by a couple of surfactants, and the HLB analysis showed that the
      required HLB of the oil was 16.7. To conclude, the pseudo-ternary diagram
      identified several characteristic regions such as emulsion, micro-emulsion, and
      separation of phases.

PMID- 20824517
TI  - Striated muscles: from molecules to cells.
AB  - Striated muscles are complex structures, composed of many cells and different
      molecules that work together to produce contraction and force. Advanced
      techniques have allowed scientists to investigate all layer of muscle
      organization. Forces ranging from piconewtons (pN) to millinewtons (mN) and
      displacements ranging from nanometers (nm) to millimetres (mm) can be measured in
      different muscle structures. The integration of different layers of analyses
      improves significantly our understanding of the mechanisms of contraction.

PMID- 20824518
TI  - Contractile performance of striated muscle.
AB  - The single muscle fiber preparation provides an excellent tool for studying the
      mechanical behaviour of the contractile system at sarcomere level. The present
      article gives an overview of studies based on intact single fibers from frog and
      mouse skeletal muscle. The following aspects of muscle function are treated: (1)
      The length-tension relationship. (2) The biphasic force-velocity relationship.
      (3) The maximum speed of shortening, its independence of sarcomere length and
      degree of activation. (4) Force enhancement during stretch, its relation to
      sarcomere length and myofilament lattice width. (5) Residual force enhancement
      after stretch. (6) Force reduction after loaded shortening. (7) Deactivation by
      active shortening. (8) Differences in kinetic properties along individual muscle
      fibers.

PMID- 20824519
TI  - Energy economy in the actomyosin interaction: lessons from simple models.
AB  - The energy economy of the actomyosin interaction in skeletal muscle is both
      scientifically fascinating and practically important. This chapter demonstrates
      how simple cross-bridge models have guided research regarding the energy economy
      of skeletal muscle. Parameter variation on a very simple two-state strain
      dependent model shows that early events in the actomyosin interaction strongly
      influence energy efficiency, and late events determine maximum shortening
      velocity. Addition of a weakly-bound state preceding force production allows weak
      coupling of cross-bridge mechanics and ATP turnover, so that a simple three-state
      model can simulate the velocity-dependence of ATP turnover. Consideration of the
      limitations of this model leads to a review of recent evidence regarding the
      relationship between ligand binding states, conformational states, and
      macromolecular structures of myosin cross-bridges. Investigation of the fine
      structure of the actomyosin interaction during the working stroke continues to
      inform fundamental research regarding the energy economy of striated muscle.

PMID- 20824520
TI  - A strain-dependency of Myosin off-rate must be sensitive to frequency to predict
      the B-process of sinusoidal analysis.
AB  - Muscle force arises as the result of many myosin molecules, each producing a
      force discrete in magnitude and in time duration. In previous work we have
      developed a computer model and a mathematical model of many myosin molecules
      acting as an ensemble and demonstrated that the time duration over which myosin
      produces force at the molecular level (referred to here as "time-on") gives rise
      to specific visco-elastic properties at the whole muscle level. That model of the
      mechanical consequences of myosin-actin interaction predicted well the C-process
      of small length perturbation analysis and demonstrated that the characteristic
      frequency 2pic provided a measure of the myosin off-rate, which is equal to the
      reciprocal of the mean time-on. In this study, we develop a mathematical
      hypothesis that a strain-dependence of the myosin off-rate at the single molecule
      level can result in a negative viscous modulus like that observed at low
      frequencies, i.e., the B-process. We demonstrate here that a simple monotonic
      strain-dependency of the myosin off-rate cannot account for the observed B
      process. However, a frequency-dependent strain-dependency, as may occur when
      visco-elastic properties of the myosin head are introduced, can explain the
      observed negative viscous modulus. These findings suggest that visco-elastic
      properties of myosin constitute the specific molecular mechanisms that underlie
      the frequency-dependent performance of many oscillatory muscles such as insect
      flight muscle and mammalian cardiac muscle.

PMID- 20824521
TI  - Electron microscopic visualization of the cross-bridge movement coupled with ATP
      hydrolysis in muscle thick filaments in aqueous solution, reminiscences and
      future prospects.
AB  - Although it has been well established that muscle contraction results from cyclic
      attachment-detachment between the cross-bridges extending from the thick
      filaments and the sites on the thin filaments, the movement of the cross-bridges
      coupled with ATP hydrolysis still remains to be a matter for debate and
      speculation. The most straightforward way to elucidate this mystery is to record
      individual cross-bridge movement in response to ATP. Using a gas environmental
      chamber (EC, or hydration chamber), with which biological specimens retaining
      their physiological function can be observed under an electron microscope, my
      coworkers and I succeeded in recording the ATP-induced individual cross-bridge
      movement in two different kinds of synthetic thick filaments in 1997 and 2008. In
      the synthetic bipolar filaments consisting of rabbit skeletal muscle myosin, the
      amplitude of cross-bridge movement exhibits a peak at 5-7.5 nm, and the direction
      of cross-bridge movement is away from, but not towards, the filament bare region
      in the absence of thin filaments. After exhaustion of ATP, the cross-bridges
      return towards their initial position, indicating that the initial cross-bridge
      state may be analogous to that after completion of power stroke. These results
      constitute the first visualization of the cross-bridge recovery stroke,
      indicating that the EC is a powerful tool to open new horizons in the research
      fields of life sciences.

PMID- 20824522
TI  - Role of titin in skeletal muscle function and disease.
AB  - This review covers recent developments in the titin field. Most recent reviews
      have discussed titin's role in cardiac function: here we will mainly focus on
      skeletal muscle, and discuss recent advances in the understanding of titin's role
      in skeletal muscle function and disease.

PMID- 20824523
TI  - Contractile characteristics of sarcomeres arranged in series or mechanically
      isolated from myofibrils.
AB  - The mechanisms of contraction are intrinsically connected to -sarcomere mechanics
      during muscle activation and relaxation. This chapter presents two sets of
      experiments performed with (1) myofibrils, in which individual sarcomeres in
      series can be evaluated during contractions, and (2) mechanically isolated
      sarcomeres. When activated at optimal length (approximately 2.0-2.4 MUm),
      myofibrils and sarcomeres produce similar forces. However, their dependence on
      length differs: sarcomeres in series in a myofibril are able to produce similar
      forces at distinct lengths, while isolated sarcomeres show a force-length
      relation that resembles that obtained in original studies performed with single
      muscle fibers. Although force in isolated sarcomeres is rapidly stabilized during
      activation, significant movements of A-band are present when the contraction is
      produced at optimal lengths, which leads to different dynamics in the two half
      sarcomeres. A-band movements decrease linearly with increasing lengths between
      2.6 and 3.6 MUm. Myofibrils and sarcomeres represent reliable techniques to
      evaluate contractile mechanisms at the most basic level of muscle organization.
      However, they present different mechanical characteristics that must be taken
      into account when scientists evaluate mechanisms of contraction.

PMID- 20824524
TI  - The force-length relationship of mechanically isolated sarcomeres.
AB  - The sarcomere force-length relationship is arguably the most basic property of
      skeletal muscle force production. It has been accepted as textbook knowledge and
      is in direct support of the sliding filament and cross-bridge theories of
      contraction. However, the sarcomere force-length relationship has never been
      measured directly. Here, we show results of two experiments elucidating the force
      length properties of mechanically isolated sarcomeres. We demonstrate that
      sarcomere forces are greatly dependent on sarcomere lengths for purely isometric
      conditions, but can take on essentially any steady-state value depending on an
      individual sarcomere's contractile history. Therefore, we conclude that steady
      state isometric forces in isolated sarcomeres do not only depend on sarcomere
      lengths (or equivalently actin-myosin overlap) but depend crucially on a
      sarcomere's contractile history. These results have direct implications for our
      understanding of the molecular mechanisms of muscle contraction.

PMID- 20824525
TI  - Extraction and replacement of the tropomyosin-troponin complex in isolated
      myofibrils.
AB  - Tropomyosin (Tm) is an essential component in the regulation of striated muscle
      contraction. Questions about Tm functional role have been difficult to study
      because sarcomere Tm content is not as easily manipulated as Troponin (Tn). Here
      we describe the method we recently developed to replace Tm-Tn of skeletal and
      cardiac myofibrils from animals and humans to generate an experimental model of
      homogeneous Tm composition and giving the possibility to measure a wide range of
      mechanical parameters of contraction (e.g. maximal force and kinetics of force
      generation). The success of the exchange was determined by SDS-PAGE and by
      mechanical measurements of calcium dependent force activation on the
      reconstituted myofibrils. In skeletal and cardiac myofibrils, the percentage of
      Tm replacement was higher than 90%. Maximal isometric tension was 30-35% lower in
      the reconstituted myofibrils than in control myofibrils but the rate of force
      activation (k(ACT)) and that of force redevelopment (k(TR)) were not
      significantly changed. Preliminary results show the effectiveness of Tm
      replacement in human cardiac myofibrils. This approach can be used to test the
      functional impact of Tm mutations responsible for human cardiomyopathies.

PMID- 20824526
TI  - Stretch and shortening of skeletal muscles activated along the ascending limb of
      the force-length relation.
AB  - There is a history dependence of skeletal muscle contraction. When muscles are
      activated and subsequently stretched, they produce a long lasting force
      enhancement. When muscles are activated and subsequently shortened, they produce
      a long-lasting force depression. The purposes of the studies shown in this
      chapter were (1) to evaluate if force enhancement and force depression are
      present along the ascending limb of the force-length (FL) relation, (2) to
      evaluate if the history-dependent properties of force production are associated
      with sarcomere length (SL) non-uniformity, and (3) to determine the effects of
      cross-bridge (de)activation on force depression. Isolated myofibrils were
      activated by either Ca2(+) or MgADP and were subjected to consecutive stretches
      or shortenings along the ascending limb of the FL relation, separated by periods
      (approximately 5 s) of isometric contraction. Force after stretch was higher than
      force after shortening when the contractions were produced at similar SLs. The
      difference in force could not be explained by SL non-uniformity. After
      shortening, MgADP activation produced forces that were higher than Ca2(+)
      activation. Since MgADP induces the formation of strongly bound cross-bridges,
      the result suggests that force depression following shortening is associated with
      cross-bridge deactivation.

PMID- 20824527
TI  - Cross-bridge properties in single intact frog fibers studied by fast stretches.
AB  - Cross-bridges properties were measured under different experimental conditions by
      applying fast stretches to activated skeletal frog muscle fiber to -forcibly
      detach the cross-bridge ensemble. This allowed to measure the tension needed to
      detach the cross-bridges, P(c), and the sarcomere elongation at the rupture
      force, L(c). These two parameters are expected to be correlated with cross
      bridges number (P(c)) and their mean extension (L(c)). Conditions investigated
      were: tetanus rise and plateau under normal Ringer and Ringer containing
      different BDM -concentrations, hyper (1.4T) and hypotonic (0.8T) solutions, 5 and
      14 degrees C temperature. P(c) was linearly correlated with the tension (P)
      developed by the fibers under all the conditions examined, however the ratio
      P(c)/P changed depending on conditions being greater at low temperature and
      higher tonicity. These results indicate that, (a) P(c) can be used as a measure
      of attached cross-bridge number and (b) the force developed by the individual
      cross-bridge increases at high temperature and low tonicity. L(c) was not
      affected by tension developed, however it changed under different conditions,
      being greater at low temperature and high tonicity. These findings, suggests, in
      agreement with P(c) data, that cross-bridge extension is smaller at low
      temperature and high tonicity. By comparing these data with tetanic tension we
      concluded that potentiation or depression induced on tetanic force by tonicity or
      temperature changes are entirely accounted for by changes of the force developed
      by the individual cross-bridge.

PMID- 20824528
TI  - Crossbridge and non-crossbridge contributions to force in shortening and
      lengthening muscle.
AB  - Analysis of tension responses to ramp length changes in muscle can provide
      important information about the crossbridge cycle. During a ramp length change,
      the force response of an active muscle shows an early change in slope (the P1
      transition) followed by a later, gradual change in slope (the P2 transition).
      Modeling shows that the first transition reflects the tension change associated
      with the crossbridge power stroke in shortening and with its reversal in
      lengthening; the reduction in slope at the second transition occurs when most of
      the crossbridges (myosin heads) that were attached at the start of the ramp
      become detached; the steady tension during shortening is borne mainly by post
      stroke heads whereas tension during lengthening is borne mostly by pre-stroke
      heads. After the P2 transition, the tension reaches a steady level in the model
      whereas in the experiments the tension continues to increase during lengthening
      or to decrease during shortening; this tension change is seen at a wide range of
      sarcomere lengths and even when active force is reduced by a myosin inhibitor. It
      appears that some non-crossbridge components in muscle fibers stiffen upon
      activation and contribute to the continued tension rise during lengthening;
      release of such tension leads to tension decline during shortening. Thus, non
      crossbridge visco-elasticity in sarcomeres may also contribute to energy storage
      and release during in situ muscle function.

PMID- 20824530
TI  - Crossbridge mechanism(s) examined by temperature perturbation studies on muscle.
AB  - An overall view of the contractile process that has emerged from -temperature
      studies on active muscle is outlined. In isometric muscle, a small rapid
      temperature-jump (T-jump) enhances an early, pre-phosphate release, step in the
      acto-myosin (crossbridge) ATPase cycle and induces a characteristic rise in force
      indicating that crossbridge force generation is endothermic (force rises when
      heat is absorbed). Sigmoidal temperature dependence of steady force is largely
      due to the endothermic nature of force generation. During shortening, when muscle
      force is decreased, the T-jump force generation is enhanced; conversely, when a
      muscle is lengthening and its force increased, the T-jump force generation is
      inhibited. Taking T-jump force generation as a signature of the crossbridge -
      ATPase cycle, the results suggest that during lengthening the ATPase cycle is
      truncated before endothermic force generation, whereas during shortening this
      step and the ATPase cycle, are accelerated; this readily provides a molecular
      basis for the Fenn effect.

PMID- 20824529
TI  - Short-range mechanical properties of skeletal and cardiac muscles.
AB  - Striated muscles are disproportionately stiff for small movements. This facet of
      their behavior can be demonstrated by measuring the force produced when the
      muscle is stretched more than about 1% of its initial length. When this is done,
      it can be seen that force rises rapidly during the initial phases of the movement
      and much less rapidly during the latter stages of the stretch. Experiments
      performed using chemically permeabilized skeletal and cardiac muscles show that
      the initial stiffness of the preparations increases in proportion with isometric
      force as the free Ca2(+) concentration in the bathing solution is raised from a
      minimal to a saturating value. This is strong evidence that the short-range
      mechanical properties of activated muscle result from stretching myosin cross
      bridges that are attached between the thick and thin filaments. Relaxed intact
      muscles also exhibit short-range mechanical properties but the molecular
      mechanisms underlying this behavior are less clear. This chapter summarizes some
      of the interesting features of short-range mechanical properties in different
      types of muscle preparation, describes some of the likely underlying mechanisms
      and discusses the potential physiological significance of the behavior.

PMID- 20824531
TI  - Efficiency of cross-bridges and mitochondria in mouse cardiac muscle.
AB  - The aim of this study was to make cellular-level measurements of the mechanical
      efficiency of mouse cardiac muscle and to use these measurements to determine (1)
      the work performed by a cross-bridge in one ATP-splitting cycle and (2) the
      fraction of the free energy available in metabolic substrates that is transferred
      by oxidative phosphorylation to free energy in ATP (i.e. mitochondrial
      thermodynamic efficiency). Experiments were performed using isolated left
      ventricular mouse papillary muscles (n = 9; studied at 27 degrees C) and the
      myothermic technique. The production of work and heat was measured during and
      after 40 contractions at a contraction frequency of 2 Hz. Each contraction
      consisted of a brief isometric period followed by isovelocity shortening. Work
      output, heat output and enthalpy output were all independent of shortening
      velocity. Maximum initial mechanical efficiency (mean +/- SEM) was 31.1 +/- 1.3%
      and maximum net mechanical efficiency 16.9 +/- 1.5%. It was calculated that the
      maximum work per cross-bridge cycle was 20 zJ, comparable to values for mouse
      skeletal muscle, and that mitochondrial thermodynamic efficiency was 72%.
      Analysis of data in the literature suggests that mitochondrial efficiency of
      cardiac muscle from other species is also likely to be between 70 and 80%.

PMID- 20824532
TI  - Mechanisms of skeletal muscle weakness.
AB  - Skeletal muscle weakness is an important feature of numerous -pathological
      conditions and it may also be a component in normal ageing. Decreased muscular
      strength can be due to decreased muscle mass and/or intrinsic defects in the
      muscle cells. In this chapter we will discuss decreased force production due to
      mechanisms intrinsic to skeletal muscle cells. We will mainly use data from mouse
      disease models to exemplify defects at various sites in the cellular activation
      contraction pathway. We will show that depending on the underlying problem,
      muscle weakness can be due decreased Ca2(+) release from the sarcoplasmic
      reticulum, reduced myofibrillar Ca2(+) sensitivity and/or decreased ability of
      the cross-bridges to generate force.

PMID- 20824533
TI  - Stretch-induced membrane damage in muscle: comparison of wild-type and mdx mice.
AB  - One component of stretch-induced muscle damage is an increase in the permeability
      of the cell membrane. As a result soluble myoplasmic proteins leak out of the
      muscle into the plasma, extracellular proteins can enter the muscle, and
      extracellular ions, including calcium, are driven down their electrochemical
      gradient into the myoplasm. In Duchenne muscular dystrophy, caused by the absence
      of the cytoskeletal protein dystrophin, stretch-induced membrane damage is much
      more severe. The most popular theory to explain the occurrence of stretch-induced
      membrane damage is that stretched-contractions cause transient mechanically
      induced defects in the membrane (tears or rips). Dystrophin, which is part of a
      mechanical link between the contractile machinery and the extracellular matrix,
      is thought to contribute to membrane strength so that in its absence mechanically
      induced defects are worse. In our view the evidence that stretch-induced muscle
      damage causes increased membrane permeability is overwhelming but the evidence
      that the increased permeability is caused by mechanically-induced defects is
      weak. Instead we review the substantial evidence that the membrane permeability
      is a secondary consequence of the mechanical events in which elevated
      intracellular calcium and reactive oxygen species are important intermediaries.

PMID- 20824535
TI  - Homocysteine, cognition and brain white matter hyperintensities.

PMID- 20824534
TI  - Cellular and whole muscle studies of activity dependent potentiation.
AB  - With a single activation, a skeletal muscle fiber, motor unit or whole muscle
      will yield a twitch contraction. The twitch is not an "all-or-none" response, but
      a submaximal response that can vary from one time to another. Prior activation
      causes myosin regulatory light chain (RLC) phosphorylation, by an enzyme called
      myosin light chain kinase. This phosphorylation dissipates slowly over the next
      several minutes due to a slow activity of light chain phosphatase.
      Phosphorylation of the RLC increases the mobility of the S1 head of myosin,
      bringing the S1 head in closer proximity to the myosin binding sites on actin.
      This increased mobility increases the rate of engagement of cross-bridges and
      increases the rate of force development and contraction magnitude on subsequent
      twitch or other submaximal contractions. We call this increased contractile
      response "activity dependent potentiation". With sequential twitches or
      incompletely fused tetanic contractions, the term staircase is used to describe
      the progressive increase in amplitude of contraction. If a twitch is elicited
      after a tetanic contraction, we call the enhanced response posttetanic
      potentiation. Stretching a muscle fiber to a longer length will also bring the
      actin filaments close to the myosin heads. This increases the Ca2(+) sensitivity,
      independent of RLC phosphorylation. At long sarcomere lengths, the impact of RLC
      phosphorylation is diminished, because Ca2(+) sensitivity is already increased.
      Similarly, lowering the temperature at which the muscle is tested increases
      Ca2(+) sensitivity. At low temperatures, staircase and posttetanic potentiation
      are diminished, but RLC phosphorylation still occurs. Activity dependent
      potentiation is an important functional modulator of contractile response.

PMID- 20824537
TI  - Supratentorial deep-seated bacterial brain abscess in adults: clinical
      characteristics and therapeutic outcomes.
AB  - PURPOSE: Supratentorial deep-seated bacterial brain abscess (BBA) in adults is
      rarely examined solely in the literature. This retrospective study is conducted
      to examine the clinical characteristics and therapeutic outcome of this specific
      group of BBA. METHODS: Eight adult patients with supratentorial deep-seated BBA,
      collected during a study period of 14 years (1994-2007), were enrolled. Their
      microbiological data derived from cerebrospinal fluid (CSF), blood or pus
      cultures, clinical features and therapeutic outcome were analyzed. RESULTS: The
      eight adult cases were six men and two women, aged 41 to 80 years (mean=61).
      Preceding medical conditions were found in five of these eight cases, while
      preceding neurosurgical event was found in one. Of the clinical presentations,
      hemiparesis (6) was the most common, followed by fever (5), altered consciousness
      (4), headache (3), septic shock (1), and seizure (1). The main locations of the
      BBA were the left basal ganglia in five, the left thalamus in two, and the right
      basal ganglia in one. Causative pathogens were found in six cases and the
      isolated pathogens were all cultured from CSF specimens. Positive bacteremia
      which grew K. pneumoniae was found in one case. Seven of these eight cases
      contracted the infection in a community-acquired state. Besides antibiotic
      treatment, seven of them received a neurosurgical intervention (stereotactic
      aspiration and/or ventriculoperitoneal shunt). The therapeutic result showed six
      cases survived and two expired. Five of the six survivors had variable degree of
      neurologic deficits. CONCLUSIONS: Besides the common clinical features of BBA,
      supratentorial deep-seated BBA has a high incidence of hemiparesis in the early
      stages of disease. Most of the involved patients have community-acquired
      infections and are preceded by a medical condition. Stereotactic aspiration for
      therapeutic and diagnostic purposes, as well as shunting surgery, is the most
      common neuro-surgical procedures used for treatment. But despite therapeutic
      efforts, high mortality and morbidity remain.

PMID- 20824536
TI  - Hyperhomocysteinemia in Alzheimer dementia patients and cognitive decline after 6
      months follow-up period.
AB  - PURPOSE: White matter hyperintensities (WMHs) on magnetic resonance imaging (MRI)
      are commonly found in Alzheimer's disease (AD) and may contribute to cognitive
      impairment. Plasma total homocysteine (tHcy) had also been linked with cognitive
      decline in AD. We examined the relationship among change of cognition, tHcy
      level, and WMHs on MRI in AD patients with a follow-up periods of 6 months.
      METHODS: AD patients with normal creatinine level and initial clinical dementia
      rating (CDR) of 1 to 2 were enrolled. tHcy and biochemistry tests related to
      cerebral vascular risk factors were collected. WMHs were measured on MRI fluid
      attenuated inverse recovery sequence and classified into deep white matter
      hyperintensities (DWMHs) and periventricular white matter hyperintensities
      (PWMHs) by visual rating scale. Neuropsychological tests including cognitive
      ability screening instrument (CASI), mini-mental state examination (MMSE)
      converted from CASI scores and CDR were collected twice during the follow- up
      period of 6 months. RESULTS: Ninety-two AD patients, 30 men and 62 women
      completed the study while the tHcy level was not significantly different between
      AD and age matched controls. tHcy level showed no correlation with CASI or MMSE
      score, at either the first or second examination. tHcy showed positive
      correlation with decline of CASI total score and abstract thinking (both p<0.01)
      but not in MMSE decline. There was no significant correlation between
      neuropsychiatric assessment and WMHs, but the decline of abstract thinking score
      was related to frontal PWMHs (R square=0.237, p=0.007). CONCLUSION: tHcy might be
      associated with rapid cognitive decline in AD after a 6-month follow-up period
      and the effect might not be directly through WMHs. tHcy level correlated with
      greater WMHs in the trigone area although greater lesion load by MRI was in the
      occipital lobe.

PMID- 20824538
TI  - Fatigue as the only clinical manifestation of colchicine induced myopathy.
AB  - PURPOSE: Fatigue may be induced by drug. Here, we reported that patients had
      fatigue after medication with colchicines. METHOD: Eight patients (8 Males, age:
      42-72 years old) had fatigue but without weakness as their chief complaints. They
      all described an inability to maintain a sustained effort, which was ameliorated
      by rest. RESULTS: The course of fatigue was insidious and progressive (mean 3.1
      2.3 months, range 1-7 months) along with medication of colchicines (mean 20.3 5.5
      months, range 11-28 months). Fatigue severity scale (patient: before drug
      withdrawal 5.41 0.19; 4 weeks after drug withdrawal 2.46 0.28; control 2.12 0.45)
      showed fatigue as their most disabling symptom, sometimes preventing them to
      carry on professional as well as socio-familial activities. The plasma creatine
      kinase elevated in these 8 patients before withdrawal of colchicines and returned
      to normal range in each subject 4 weeks after drug withdrawal. A probable
      diagnosis of drug-induced fatigue was made when symptom subsided after
      colchicines were discontinued. CONCLUSION: It is emphasized that side effect of
      drug should be considered as a differential diagnosis of fatigue in patients
      having colchicines. Early recognition and diagnosis will prevent serious muscle
      damage.

PMID- 20824539
TI  - Tuberculosis with meningitis, myeloradiculitis, arachnoiditis and hydrocephalus:
      a case report.
AB  - PURPOSE: Involvement of the central nervous system (CNS) by tuberculosis is rare;
      it can affect either immunocompromised or immunocompetent people. CASE REPORT:
      Here, we report a case of tuberculosis with CNS involvement. We present the case
      of an immunocompetent young man who developed fever, subacute headache,
      disturbance of consciousness, paraparesis, sphincter dysfunction, and
      hypoesthesia. The final diagnosis was tuberculous meningitis, myeloradiculitis
      and arachnoiditis based on clinical signs, imaging studies, and cerebrospinal
      fluid culture. The patient received antituberculosis medication with adjunct
      intravenous steroid therapy. Although his clinical condition improved
      significantly, some neurological sequelae persisted. CONCLUSION: Methods for
      detection of CNS TB and treatment protocols should be constantly re-evaluated to
      improve treatment outcome and reduce likelihood and severity of neurological
      sequelae.

PMID- 20824540
TI  - Exercise related spinal cord infarction: a case report.
AB  - PURPOSE: A sudden elevation of the intervertebral disc pressure could result in
      injection of cartilaginous material into spinal small caliber vessels causing
      embolism of the underlying vessels is well documented but rarely occurs. CASE
      REPORT: Here we present a patient with sudden onset of weakness over left upper
      extremity several minutes after neck rotation exercise. The symptoms were
      progressive with quadra-paresis and urine incontinence without cranial nerve or
      sensory function deficit. The cervical spine MRI showed cervical spondylosis with
      degenerative osteophytes of lower cervical-spine with mild indentation of the
      thecal sac. There was also focal T2-high intensity edema of "H" gray matters of
      C3 spinal cord. According to the preliminary examination and clinical course, the
      symptoms of the patient can be explained by the ischemia of spinal cord secondary
      to fibrocartilaginous embolism(FCE) derived from intervertebral discs. After
      aspirin and IV dexamethasone treatment, the clinical condition of the patient
      improved significantly. CONCLUSION: Neck rotation exercise is common among all
      kinds of relaxation or physical rehabilitation activities. However, the potential
      unwanted effects of this exercise suggest that one should be aware of the
      potential adverse neurologic outcomes especially inappropriate non- professional
      method.

PMID- 20824541
TI  - Protean neuroimaging presentations in an adult with Klebsiella pneumoniae
      infection.
AB  - PURPOSE: To report on the findings of a series of cranial computed tomography
      (CT) and magnetic resonance (MR) imaging studies of a 57-years-old woman with
      Klebsiella (K.) pneumoniae infection. CASE REPORT: The patient had fever,
      consciousness disturbance and left hemiplegia as the initial presentations of K.
      pneumoniae infection. Initial blood culture grew K. pneumoniae, and a delayed
      purulent cerebrospinal fluid profile was found later. The serial neuroimaging
      studies showed cerebral hemorrhage, cerebritis and subsequent multiple abscess
      formations. In the meanwhile hepatic and pulmonary abscess were also discovered
      by imaging studies. With a 77- days intravenous ceftriaxone treatment (4 gm/day),
      the abscess formations of brain, lung and liver were all resolved. CONCLUSION:
      This study showed the protean neuroimage features of a woman with K. pneumoniae
      infection and the confirmation of multiple brain abscesses was made by follow-up
      neuroimaging studies. These sequential neuroimage findings in one patient are
      uncommon but deserved special clinical note by the first-line, primary-care
      physicians including neurologists.

PMID- 20824542
TI  - Lateral medullary infarction presenting as Brown-Sequard syndrome-like
      manifestation: a case report and literature review.
AB  - PURPOSE: Lateral medullary infarction is not uncommon in clinical practice of
      neurology. This report describes a patient who initially presented with Brown
      Sequard syndrome-like manifestation but was later diagnosed with acute infarction
      in the left lower lateral medulla. CASE REPORT: A 65-year-old woman presented
      with acute onset of unsteadiness, left side hemiparesis, left limb dysmetria,
      left side partial Horner syndrome, and paresthesia in the right lower limb and
      trunk with a sensory level at T5 on the right. No bulbar symptoms nor facial
      paresthesia was noted. Brown- Sequard syndrome was suspected initially, but
      cervical spine magnetic resonance imaging showed only mild spinal stenosis. Brain
      magnetic resonance imaging revealed acute infarction in the left lower lateral
      medulla. The mechanism of this unusual presentation is discussed. CONCLUSION:
      Brown-Sequard syndrome-like manifestation can be a rare presentation of lower
      lateral medullary infarction.

PMID- 20824543
TI  - Recurrent multiple cranial neuropathies in a diabetic patient.
AB  - PURPOSE: Multiple cranial neuropathies is one of the neurological complications
      among diabetic patients. Symptoms of multiple cranial neuropathies may cause
      great anxiety for these patients and often appear to be a serious problem from a
      diagnostic and therapeutic point of view. A correct and timely diagnosis of the
      underlying cause of cranial nerve palsy in these patients is crucial because of
      the realistic threat of devastating neurologic conditions. CASE REPORT: Recurrent
      cranial neuropathies involving different cranial nerves are unusual. In this case
      report, we present a diabetic patient with four episodes of recurrent cranial
      neuropathies including two times of facial neuropathies and two episodes of
      external ophthalmoplegia within 2 years. CONCLUSION: Diabetic cranial
      neuropathies may appear in a recurrent pattern; spontaneous remission is the
      rule.

PMID- 20824544
TI  - [Parkinson's disease and cortico-Basal Ganglia circuits].
AB  - Cortico-basal ganglia circuit model has been studied extensively after it was
      first proposed by Alexander and Crutcher in 1990. This model accurately predicted
      the hyperactivity of indirect pathway and subthalamic nucleus(STN) in the
      dopamine deficiency state of Parkinson's disease (PD), prompting the experimental
      approaches of lesioning STN in parkinsonian primates. Application of these
      successful experiences with STN lesions in the reversal of parkinsonian symptoms
      to human PD patients facilitates the development of STN deep brain stimulation
      (DBS), which has become one of the most important therapies for PD in recent
      years. Although the classical model of the cortico-basal ganglia circuits by
      Alexander and Crutcher has provided many important insights into the basal
      ganglia function, the functional role of cortico-subthalamic "hyperdirect"
      pathway in the circuits has been relatively neglected. The first part of this
      article summarizes recent development concerning the cortico-basal ganglia
      circuits, especially emphasizing the importance of the hyperdirect pathway. In
      the second part of this article, we would describe the analyses of gross
      corticobasal ganglia circuit electrophysiological findings, especially
      emphasizing the coherence between two oscillating signals. We would also discuss
      the correlation between these parameters and the motor dysfunction, and its
      pathophysiological implications in PD.

PMID- 20824545
TI  - Management of sexuality problem in quadriplegia: a brief summary.
AB  - Quadriplegia is a serious group of spinal disability. Cases with quadriplegia
      usually present unsatisfactory sexual life. In male, the main problem is the
      ability to reach orgasm deficient. In female, pregnancy problem should be noted.
      Management of sexuality problem in quadriplegia is of interest. In this article,
      the author will briefly review on this topic.

PMID- 20824546
TI  - A 5th cerebral ventricle in an aged woman: pictorial neurological disease.

PMID- 20824547
TI  - Factors associated with abandonment of infants born to HIV-positive women:
      results from a Ukrainian birth cohort.
AB  - Social marginalisation and other challenges facing HIV-positive pregnant women in
      Ukraine may put them at increased risk of relinquishing their infants to the
      state. We described rates of infant abandonment (exclusive non-parental care to
      most recent follow-up, censored at two years of age) and investigated associated
      factors using logistic regression models, in 4759 mother-infant pairs enrolled
      across six Ukrainian sites in the European Collaborative Study from 2000 to May
      2009. Median maternal age was 26.0 years, 81.8% were married or cohabiting and
      60.6% were nulliparous at enrolment. An injecting drug use (IDU) history was
      reported by 18.4%, 80.2% took antiretroviral therapy (ART) antenatally and most
      deliveries were vaginal. A small but significant proportion of infants had been
      cared for exclusively in institutions by their second birthday (2.1% overall),
      decreasing from 3.8% (15/393) in 2000-2002 to 1.6% (49/3136) in 2006-2009
      (p<0.01), concurrent with prevention of mother-to-child transmission scale-up. A
      further 1% of infants spent some time in non-parental care. Antenatal ART was
      associated with an 88% reduced abandonment risk (adjusted odds ratio (AOR) 0.12),
      versus receipt of single dose nevirapine only, and this was reflected in HIV
      infection prevalence in the two groups (17.1% of abandoned infants versus 6.6% in
      parental care). Mothers without a cohabiting partner or husband were more likely
      to abandon (AOR 4.08), as were active IDUs (AOR 3.27) and those with >=1 previous
      children (AOR 1.89 for second-born and AOR 2.56 for subsequent births). Women
      delivering by elective caesarean section were less likely to abandon (AOR 0.37
      versus vaginal), as were those leaving full-time education later (AOR 0.61 for 17
      18 years versus <=16 years and AOR 0.23 for >=19 years versus <=16 years).
      Interventions to extend family planning and IDU harm reduction services along
      with non-stigmatising antenatal care to marginalised women are needed, and may
      reduce abandonment.

PMID- 20824548
TI  - Evaluating counseling outcome on adherence to prophylaxis and follow-up after
      sexual HIV-risk exposure: a randomized controlled trial.
AB  - OBJECTIVE: Post-exposure prophylaxis (PEP) is recommended for the management of
      sexual HIV-risk exposure. However, a high percentage of exposed patients
      discontinue both their 28-day prophylaxis course before 15 days and HIV testing
      follow-up before M3. The objective of this study is to assess the efficacy of a
      counseling intervention in enhancing both adherence to PEP and HIV testing follow
      up. METHODS: Between 1 June 2004 and 31 December 2005, 54 patients exposed to
      sexual HIV-risk exposure were included in a multicenter, prospective, controlled,
      randomized trial, comparing a group receiving a counseling intervention in
      addition to traditional medical management (intervention group (IG), n=28) vs. a
      control group (CG, n=26). Patients in the IG received interactive counseling
      interventions focused on adherence to PEP and to HIV testing follow-up, led by
      specially trained nurses. The main outcome measures were proportion of patients
      achieving 100% adherence to PEP as evaluated on D15 by a self-completed patient
      questionnaire and on HIV testing on D45 and M3. RESULTS: Groups were well
      balanced at baseline for age, sex, and circumstances of exposure. The proportion
      of 100% adherent patients to PEP was significantly higher in the IG compared to
      the CG (54% vs. 23%, p=0.036). Patients in the IG were more likely to complete
      the HIV testing follow-up at D45 (86% vs. 54%, p=0.023) and M3 (68% vs. 38%,
      p=0.056). CONCLUSIONS: This study suggests the effectiveness of a counseling
      program to enhance adherence to both PEP and HIV testing follow-up after sexual
      exposure.

PMID- 20824549
TI  - HIV-infected patients and treatment outcomes: an equivalence study of community
      located, primary care-based HIV treatment vs. hospital-based specialty care in
      the Bronx, New York.
AB  - The HIV-infected population in the USA is expanding as patients survive longer
      and new infections are identified. In many areas, particularly rural/medically
      underserved regions, there is a growing shortage of providers with sufficient HIV
      expertise. HIV services incorporated into community-based (CB), primary care
      settings may therefore improve the distribution and delivery of HIV treatment.
      Our objective was to describe/compare patients and treatment outcomes in two
      settings: a community-located, primary care-based HIV program, and a hospital
      based (HB) specialty center. CB providers had on-site access to generalist HIV
      experts. The hospital center was staffed primarily by infectious disease
      physicians. This was a retrospective cohort study of 854 HIV-positive adults
      initiating care between 1/2005 and 12/2007 within an academic medical center
      network in the Bronx, NY. Treatment outcomes were virologic and immunologic
      response at 16-32 and 48 weeks, respectively, after combination antiretroviral
      therapy (cART) initiation. We found that HB subjects presented with a higher
      prevalence of AIDS (59% vs. 46%, p<0.01) and lower initial CD4 (385 vs. 437,
      p<0.05) than CB subjects. Among 178 community vs. 237 hospital subjects starting
      cART, 66% vs. 62% achieved virologic suppression (95% confidence interval (CI)
      difference -0.14-0.06) and 49% vs. 59% achieved immunologic success, defined as a
      100 cell/mm3 increase in CD4 (95% CI difference 0.00-0.19). The multivariate
      adjusted likelihoods of achieving viral suppression [OR=1.24 (95% CI 0.69-2.33)]
      and immunologic success [OR=0.76 (95% CI 0.47-1.21)] were not statistically
      significant for community vs. hospital subjects. Because this was an
      observational study, propensity scores were used to address potential selection
      bias when subjects presented to a particular setting. In conclusion, HIV-infected
      patients initiate care at CB clinics earlier and with less advanced HIV disease.
      Treatment outcomes are comparable to those at a HB specialty center, suggesting
      that HIV care can be delivered effectively in community settings.

PMID- 20824550
TI  - Psychological distress among persons living with HIV, hypertension, and diabetes.
AB  - It has been assumed that receipt of a diagnosis of HIV is a uniquely distressing
      event, more so than with any other illness. The present study compared the mean
      scores on the Hopkins Symptom Checklist, a measure of emotional distress, of
      South African patients living with HIV/AIDS, hypertension, diabetes, and both
      hypertension and diabetes. The differences among the four groups were non
      significant, suggesting that living with HIV/AIDS may be no more emotionally
      distressing than other common chronic illnesses. In this research note, it is
      speculated that these findings may be accounted for in terms of the high
      prevalence of HIV in South Africa, the recent availability of antiretroviral
      treatment resulting in HIV being seen as a chronic illness rather than a death
      sentence, and the base rate of mental health problems among the South African
      population.

PMID- 20824551
TI  - Associations between alcohol misuse and risks for HIV infection among men who
      have multiple female sexual partners in Cape Town, South Africa.
AB  - The occurrence of high rates of alcohol consumption in a context of high HIV
      prevalence in South Africa poses a significant health challenge for this country.
      This paper aims to answer three questions that could further our knowledge
      regarding the links between alcohol use and HIV infection: (a) "Are problem
      drinkers more likely to have multiple concurrent partners than those who are
      not?"; (b) "Are condoms applied less effectively and less consistently by problem
      drinkers compared to those who are not?"; (c) "Are the female sexual partners of
      problem drinkers different from those who are not?" Two cross-sectional HIV bio
      behavioural surveillance surveys using Respondent-Driven Sampling were conducted
      in two peri-urban settings on the outskirts of Cape Town, South Africa. Eight
      hundred and forty-eight men aged 25-55 years who have multiple, concurrent female
      sexual partners were recruited. Problem drinkers had a score of >=3 on the CAGE
      questionnaire. Questions enquired about partner numbers, condom use and partner
      traits. Multivariate logistic regression models were developed to determine
      significant associations between outcome variables and problem drinking. Fifty
      eight percent of men were problem drinkers. Compared to non-problem drinkers,
      problem drinkers were significantly more likely to report having any symptom of a
      STI; not using condoms due to drinking; inconsistent condom use with all partner
      types; that their most recent once-off partner was unemployed; having met their
      most recent partner at an alcohol-serving venue; and having had a once-off sexual
      relationship. Alcohol may fuel once-off sexual encounters, often characterised by
      transactional sex and women's limited authority to negotiate sex and condom use;
      factors that can facilitate transmission of HIV. HIV prevention interventions
      specifically targeting drinkers, the contexts in which problem drinking occurs
      and multiple sexual partnering are urgently needed.

PMID- 20824553
TI  - "It took a piece of me": initial responses to a positive HIV diagnosis by
      Caribbean people in the UK.
AB  - How do people respond to the news that they are HIV positive? To date, there have
      been few published qualitative studies of HIV diagnosis experiences, and none
      focusing on Caribbean people. Twenty-five HIV-positive Caribbean people in
      London, UK, related their diagnosis experience and its immediate aftermath in
      semi-structured interviews. Diagnosis with HIV caused profound shock and distress
      to participants, as they associated the disease with immediate death and
      stigmatisation. The respondents struggled with "biographical disruption", the
      radical disjuncture between life before and after diagnosis, which led them into
      a state of liminality, as they found themselves "betwixt and between" established
      structural and social identities. Respondents were faced with multifaceted loss:
      of their known self, their present life, their envisioned future and the partner
      they had expected to play a role in each of these. A minority of accounts suggest
      that the way in which healthcare practitioners delivered the diagnosis
      intensified the participants' distress. This research suggests that healthcare
      practitioners should educate patients in specific aspects of HIV transmission and
      treatment, and engage closely with them in order to understand their needs and
      potential reactions to a positive diagnosis.

PMID- 20824552
TI  - Anxiety/stress among mothers living with HIV: effects on parenting skills and
      child outcomes.
AB  - Parental HIV infection has been associated with negative outcomes for children,
      and parenting skills appear to be one mechanism operating in that association.
      The present study focuses on the relations between maternal stress, parenting,
      and child functioning among families where the mother is living with HIV. Sixty
      nine mothers with at least one child between six and 12 years old completed
      questionnaires at the baseline assessment of an intervention designed to
      facilitate maternal disclosure of HIV status. Respondents were assessed using
      multiple measures of stress/anxiety, parenting skills, and child outcomes,
      including the Parenting Stress Index, the RAND Mental Health Inventory, the
      Family Routines Questionnaire, and the Child Behavior Checklist. Covariance
      structural modeling was used to assess the variable relationships, with latent
      constructs created for maternal anxiety/stress, parenting skills, and child
      problem behaviors (both direct and indirect effects were evaluated, with a model
      based bootstrap used to verify model stability). Results demonstrated that
      maternal stress was negatively associated with a broad range of parenting skills,
      and that parenting skills were negatively associated with child problem
      behaviors. Mothers living with HIV who are anxious about their own health and
      functioning, and who were more stressed in their parental role, were more likely
      to exhibit poorer parenting skills - specifically to engage children less
      frequently in family routines (e.g., eating meals together, having a bedtime
      routine), poorer parent-child communication, and poorer and less consistent
      parenting discipline. Not uncommonly, mothers living with HIV experience a range
      of stressors above and beyond those related to their illness (e.g., poverty,
      residence in high risk and low resource communities, discrimination). Results
      demonstrate the need for interventions designed to decrease maternal stress and
      enhance parenting skills for families affected by HIV.

PMID- 20824554
TI  - The feasibility and acceptability of male circumcision among men, women, and
      health providers of the Altagracia Province, Dominican Republic.
AB  - BACKGROUND: Male circumcision (MC) is an effective strategy to reduce the risk of
      HIV acquisition in men. The objective of the present study was to evaluate the
      feasibility of introducing MC in the Altagracia Province and to qualitatively
      assess the knowledge and acceptability of MC among men, women, and health
      providers. METHODS: Two surveys were administered to providers. The first,
      assessed their experience and knowledge of MC and the second, a "Health Facility
      Profile," included an inventory of available surgical materials in the clinics.
      Fourteen focus group discussions were conducted to evaluate the acceptability of
      MC. RESULTS: Forty-three providers were interviewed at 37 clinics. Median age was
      33 years (range 23-55 years). Most were physicians (91%) employed by the
      government. Only 23% had experience with MC. Almost universally (95%), providers
      knew that MC has health benefits. All agreed that MC improves hygiene and 67%
      knew that MC decreases the risk of HIV infection. Only six clinics provided HIV
      counseling and testing and most lacked adequate surgical facilities and
      equipment. Findings of the qualitative study showed that about half the men and
      the majority of women were accepting of MC. CONCLUSIONS: Men, women, and
      providers in the Dominican Republic may be accepting of MC. Education about the
      benefits of the procedure is needed in the community.

PMID- 20824555
TI  - HIV-positive women in Australia explain their use and non-use of antiretroviral
      therapy in preventing mother-to-child transmission.
AB  - This paper explores HIV-positive women's accounts of their use and non-use of
      treatments for the prevention of mother-to-child transmission. In-depth
      interviews were conducted in 2001 with 34 HIV-positive women who were diagnosed
      during their childbearing years. This paper reports on the 16 women who gave
      birth after being diagnosed with HIV. Some women reported experiencing
      debilitating side-effects of antiretroviral (ARV) therapy, and all were aware
      that the history of HIV therapy was not one of clear, consistent and benevolent
      effectiveness. It was evident that women wanted the best outcomes for themselves
      and their babies. Women represented their role vis-a-vis their children as
      encompassing protection against a medical fraternity that insisted on the use of
      ARV and prophylaxis without acknowledging the mothers' concerns about toxicity.
      From the women's perspective, it made sense not to let their babies become
      experimental subjects when long-term effects were unknown. To maximise the
      benefit of ARV therapy to mothers and babies, thereby reducing the risk of
      vertical transmission, it is imperative to understand a woman's explanation of
      what therapy means to her, and advisable to presume that she wants the best for
      her baby. Such an approach will facilitate better communication and encourage
      clinicians and patients to work towards a shared goal.

PMID- 20824556
TI  - Sociocultural facilitators and barriers to condom use during anal sex among men
      who have sex with men in Guangzhou, China: an ethnographic study.
AB  - This ethnographic study explored how cultural belief systems shaped sexual risk
      practices among men who have sex with men (MSM) in Guangzhou, China. A specific
      focus was on how these men's sexual practices varied across sexual venues and
      among different partners in order to better understand sociocultural facilitators
      and barriers to condom use in the Guangzhou community. Qualitative data were
      obtained through semi-structured in-depth interviews with MSM and ethnographic
      observations in MSM sexual venues in the city. The thematic analysis focused
      specifically on the accounts of unprotected sex occasions. We found that an
      erotic idea of "rouyu" (desire of physical flesh) embedded in a subculture of MSM
      and a metaphor for condom use as being inferior and promoting distance posed a
      considerable barrier to condom use among these MSM. Some men reported gaining a
      positive self-concept related to same-sex identity through unprotected sex. These
      MSM's subjective evaluations of HIV risk were closely tied to the perceived
      characteristics of sex partners and sexual venues. We conclude by advocating
      specific sociocultural interventions in emerging risk venues, such as
      saunas/bathhouses, to better meet the needs of the MSM community in Guangzhou.

PMID- 20824557
TI  - Disclosure of HIV results among discordant couples in Rakai, Uganda: a
      facilitated couple counselling approach.
AB  - Disclosure of HIV sero-positive results among HIV-discordant couples in sub
      Saharan Africa is generally low. We describe a facilitated couple counselling
      approach to enhance disclosure among HIV-discordant couples. Using unique
      identifiers, 293 HIV-discordant couples were identified through retrospective
      linkage of married or cohabiting consenting adults individually enrolled into a
      cohort study and into two randomised trials of male circumcision in Rakai,
      Uganda. HIV-discordant couples and a random sample of HIV-infected concordant and
      HIV-negative concordant couples (to mask HIV status) were invited to
      sensitisation meetings to discuss the benefits of disclosure and couple
      counselling. HIV-infected partners were subsequently contacted to encourage HIV
      disclosure to their HIV-uninfected partners. If the index positive partner
      agreed, the counsellor facilitated the disclosure of HIV results, and provided
      ongoing support. The proportion of disclosure was determined. Eighty-one per cent
      of HIV-positive partners in discordant relationships disclosed their status to
      their HIV-uninfected partners in the presence of the counsellor. The rates of
      disclosure were 81.3% in male HIV-positive and 80.2% in female HIV-positive
      discordant couples. Disclosure did not vary by age, education or occupation. In
      summary, disclosure of HIV-positive results in discordant couples using
      facilitated couple counselling approach is high, but requires a stepwise process
      of sensitisation and agreement by the infected partner.

PMID- 20824558
TI  - Comparing regret of disclosing HIV versus sexual orientation information by MSM.
AB  - Very little research has been conducted focusing on regret associated with
      disclosing either HIV-positive serostatus or sexual orientation information. The
      purpose of this study was to investigate the prevalence of regret related to the
      disclosure of serostatus and sexual orientation to family members among HIV
      positive men who have sex with men (MSM) and to further explore the participant,
      family member, and relationship characteristics that influence the likelihood of
      experiencing regret. Almost half of participants indicated no regret with the
      disclosure of either HIV-positive serostatus or sexual orientation. Among those
      that did experience some regret, the prevalence of regret with at least one
      family member was similar for HIV-positive serostatus (39.4%) and for sexual
      orientation (37.3%). Suggestions for professionals working with HIV-positive MSM
      and implications for future research are presented.

PMID- 20824559
TI  - Are men testing? Sex differentials in HIV testing in Mpumalanga Province, South
      Africa.
AB  - HIV testing is the centerpiece of the national AIDS program in South Africa and
      many HIV-endemic countries, yet there is surprisingly little published data on
      who uses testing services. In 2006, we conducted a census of HIV-testing records
      in all 282 public and non-governmental voluntary counseling and testing (VCT)
      sites in Mpumalanga (MP), South Africa, the province with the highest HIV
      prevalence in the country. We secured data on the age and sex of all those tested
      in 260 sites since the year testing was initiated, as far back as 1998 in some
      sites. For the year 2006, we also secured data on whether a client came to VCT
      through self-referral, antenatal services (prevent mother-to-child transmission
      (PMTCT)), or medical referral. The results characterize the rapid uptake of
      testing as facilities increased, with the number of people testing in MP more
      than doubling each year between 2002 and 2006. However, there is a persistent 3:1
      differential of females:males testing, with 72.7% of all testing among females.
      When pregnancy-related testing (via PMTCT) is excluded, females still account for
      65.1% of all testing in MP. The data also suggest men are more likely to test at
      older ages and as a result of medical referral. In summary, females in MP are far
      more likely to use HIV testing than males, even after accounting for increased
      access to testing during pregnancy. Sex differentials in HIV testing warrant
      closer policy attention.

PMID- 20824560
TI  - Who is the vulnerable child? Using survey data to identify children at risk in
      the era of HIV and AIDS.
AB  - Over the past decade, there has been increasing global attention to mitigating
      the impacts of the HIV/AIDS epidemic on children's lives. Within this context,
      developing and tracking global child vulnerability indicators in relation to HIV
      and AIDS has been critical in terms of assessing need and monitoring progress.
      Although orphanhood and adult household illness (co-residence with a chronically
      ill or HIV-positive adult) are frequently used as markers, or definitions, of
      vulnerability for children affected by HIV and AIDS, evidence supporting their
      effectiveness has been equivocal. Data from 60 nationally representative
      household surveys (36 countries) were analyzed using bivariate and multivariate
      methods to establish if these markers consistently identified children with worse
      outcomes and also to identify other factors associated with adverse outcomes for
      children. Outcome measures utilized were wasting among children aged 0-4 years,
      school attendance among children aged 10-14 years, and early sexual debut among
      adolescent boys and girls aged 15-17 years. Results indicate that orphanhood and
      co-residence with a chronically ill or HIV-positive adult are not universally
      robust measures of child vulnerability across national and epidemic contexts. For
      wasting, early sexual debut, and to a lesser extent, school attendance, in the
      majority of surveys analyzed, there were few significant differences between
      orphans and non-orphans or children living with chronically ill or HIV-positive
      adults and children not living with chronically ill or HIV-positive adults. Of
      other factors analyzed, children living in households where the household head or
      eldest female had a primary education or higher were significantly more likely to
      be attending school, better household health and sanitation was significantly
      associated with less wasting, and greater household wealth was significantly
      associated both with less wasting and better school attendance. Of all marker of
      child vulnerability analyzed, only household wealth consistently showed power to
      differentiate across age-disaggregated outcomes. Overall, the findings indicate
      the need for a multivalent approach to defining child vulnerability, one which
      incorporates household wealth as a key predictor of child vulnerability.

PMID- 20824561
TI  - Predictive factors and incidence of anxiety and depression in a cohort of HIV
      positive patients in French Guiana.
AB  - A retrospective cohort study was conducted to determine the predictive factors
      and the incidence of anxiety and depression in a cohort of patients followed in
      French Guiana. A total of 2315 patients were followed for a total of 9116 years
      of follow-up. The incidence rate of first observed depression was 1.89 per 100
      person years. The incidence rate of first observed generalized anxiety was 1.27
      per 100 person years. A single failure Cox proportional hazards model showed that
      patients diagnosed <1 year (Hazard ratio (HR)=4.15; 95% CI=1.15-14.9; P=0.029),
      patients treated <one year (HR=3.2; 95% CI=1.7-6.2; P<0.001), patients with
      anxiety (HR=37; 95% CI=19-72; P<0.001), females (HR=2.5; 95% CI=1.5-4; P<0.001),
      French citizens (HR=1.6; 95% CI=1.05-2.5; P=0.029), and patients with severe
      immunodeficiency (HR=3.7; 95% CI=1.7-7.8; P=0.001) were at increased risk of
      depression. For anxiety, recently diagnosed patients (HR=11.7; 95% CI=3.2-42;
      P<0.001) and females (HR=3; 95% CI=1.6-5.8; P=0.001) were at increased risk. The
      hazard function showed that there were three peaks for anxiety (2, 6, and 11
      years) and depression (2, 7, and 14 years). Incidence of anxiety and depression
      in this HIV cohort is high. Knowledge of this pattern may help physicians be more
      vigilant to psychological distress at certain phases of life with HIV.

PMID- 20824562
TI  - Mamekhaya: a pilot study combining a cognitive-behavioral intervention and mentor
      mothers with PMTCT services in South Africa.
AB  - Nearly 30% of pregnant women in South Africa are estimated to be HIV
      seropositive, yet adherence to guidelines for the prevention of mother-to-child
      transmission of HIV (PMTCT) is often low. A pilot study was developed to see
      whether PMTCT services provided by the South African Government could be enhanced
      by the Mamekhaya program, a combination of the mothers2mothers peer-mentoring
      program and a culturally adapted cognitive-behavioral intervention (CBI) from the
      USA. Pregnant women attending two maternity clinics offering PMTCT in Gugulethu
      and Vanguard Townships, Cape Town, South Africa, were invited to participate in
      the study. Women at the intervention site (Gugulethu) received the support of a
      mentor mother and also attended an eight-session Mamekhaya CBI. At the control
      site (Vanguard), women received standard services provided by midwives and
      counselors. Baseline assessments were completed by all participants at enrollment
      (n=160), and follow-ups were completed six months later by 44% of participants.
      Self-reports of adherence to PMTCT practices were high across both sites (90% or
      more engaging in the core practices). Women at the Mamekhaya site showed
      significantly greater improvement in establishing social support and reducing
      depression scores than women at the control site. Mamekhaya participants also
      showed trends for better attendance at follow-up medical visits, and greater
      improvements in positive coping. The greatest effect of the Mamekhaya program was
      to increase HIV knowledge scores, particularly with regard to understanding the
      meaning and importance of viral load and CD4 test results. Results from this
      pilot study show promise that augmenting basic PMTCT services with mentor mothers
      and a culturally adapted CBI can be effective in conveying information and in
      improving the emotional outlook and hopefulness of HIV-positive pregnant women in
      South Africa.

PMID- 20824563
TI  - Factors influencing uptake of HIV care and treatment among children in South
      Africa - a qualitative study of caregivers and clinic staff.
AB  - Despite antiretroviral therapy rollout in South Africa, fewer children than
      expected are accessing HIV care services. Our objectives were to describe
      barriers and facilitators of uptake of HIV care among children. Our study
      involved six private-sector clinics which provide HIV care free-of-charge in and
      around Gauteng province, South Africa. In-depth interviews were conducted in July
      2008 with 21 caregivers of HIV-infected children attending these clinics, 21
      clinic staff members and three lead members of staff from affiliated care
      centres. Many children were only tested for HIV after being recurrently unwell.
      The main facility-related barriers reported were long queues, negative staff
      attitudes, missed testing opportunities at healthcare facilities and provider
      difficulties with paediatric counselling and venesection. Caregivers reported
      lack of money for transport, food and treatments for opportunistic infections,
      poor access to welfare grants and lack of coordination amongst multiple
      caregivers. Misperceptions about HIV, maternal guilt and fear of negative
      repercussions from disclosure were common. Reported facilitators included
      measures implemented by clinics to help with transport, support from family and
      day-care centres/orphanages, and seeing children's health improve on treatment.
      Participants felt that better public knowledge about HIV would facilitate uptake.
      Poverty and the implications of children's HIV infection for their families
      underlie many of these factors. Some staff-related and practical issues may be
      addressed by improved training and simple measures employed at clinics. However,
      changing caregiver attitudes may require interventions at both individual and
      societal levels. Healthcare providers should actively promote HIV testing and
      care-seeking for children.

PMID- 20824564
TI  - A comparison of risk factors for atypical squamous cells and squamous
      intraepithelial lesions in a sample of US- and African-born HIV-positive women.
AB  - Previous research conducted in the USA and Africa has identified human
      immunodeficiency virus (HIV) infection as a risk factor for women developing
      squamous intraepithelial lesion (SIL) diagnosis. This study was conducted to
      compare the odds of a diagnosis of atypical squamous cells (ASCUS) or SIL in a
      sample of mostly African-born and US-born women (n=275). A greater proportion of
      US-born women had an ASCUS (68.9%) or SIL (81.3%) diagnosis than African-born
      women (29.5% ASCUS, 15.6% SIL). After adjusting for age, smoking status, absolute
      CD4, and a prescription for HIV-antiviral medications, the US-born women had a
      greater odds of a SIL diagnosis than the African-born women (OR=0.22, 95% CI:
      0.06-0.79); no significant differences in ASCUS remained after adjustment. In
      this sample, proportionately more African-American (55.3%) and white American
      (51.1%) women smoke tobacco than African-born women (1.9%), explaining, perhaps,
      some of the difference. We found that an absolute CD4 less than 200, when
      compared to an absolute CD4 above 500, was highly predictive of a SIL diagnosis
      (OR=6.31, 95% CI: 2.10-18.93, p-trend <0.01). A prescription for HIV-antiviral
      medications was not a significant predictor of an ASCUS or SIL diagnosis.

PMID- 20824565
TI  - Outcomes and challenges of scaling up comprehensive PMTCT services in rural
      Swaziland, Southern Africa.
AB  - To mitigate the negative impacts of HIV infection on pregnant women and their
      children, comprehensive services to prevent mother to child transmission are
      required. We report the outcomes and challenges of a comprehensive service to
      prevent mother to child transmission of HIV infection implemented from January to
      December 2007 in a referral hospital and its rollout clinics in rural Swaziland,
      Southern Africa. We reviewed monthly reports, hospital registers, and field
      diaries and interviewed 64 service providers. A total of 460 HIV tests were done
      on first and repeat antenatal care visits. From the test done, 93.7% of the
      results were collected. About 69.1% of first-time visitors accepted HIV test. The
      antenatal coverage of pregnant women with nevirapine (NVP)+/-zidovudine (AZT) was
      100%. Of 443 antenatal and post-natal care women who underwent CD4 test, 54.4%
      collected results. About 16.3% of those who collected results were started on
      antiretroviral treatment. The percentage of postpartum women discharged with
      unknown HIV status fell by 64.8%. About 91.5% of HIV-positive women received
      intrapartum antiretroviral prophylaxis of stat dose NVP and AZT + lamivudine with
      1-week postpartum tail. From the exposed newborns, 98.8% received NVP stat dose
      and AZT. A total of 304 HIV exposed infants of age six weeks to 18 months
      underwent DNA-PCR test. The prevalence of infection among infants where both
      mother and infant received antiretroviral prophylaxis was 16.1% (n=243). HIV test
      acceptance rate at first antenatal care visit, proportion of clients collecting
      CD4 and DNA-PCR test results were low and call for mechanisms for improvement.
      The proportion of DNA-PCR-positive exposed infants in this study was higher than
      other reports from Southern Africa. The variation of the findings could be
      explained by mode of infant feeding, age of testing and mode of delivery.
      Provision of comprehensive prevention of mother to child transmission services in
      resource limited setting is possible but challenged by staff shortage, socio
      economic and service-related factors.

PMID- 20824566
TI  - Harmful alcohol consumption and patterns of substance use in HIV-infected
      patients receiving antiretrovirals (ANRS-EN12-VESPA Study): relevance for
      clinical management and intervention.
AB  - Alcohol abuse affects secondary prevention and disease progression in HIV
      infected patients, and adherence and response to treatment in those chronically
      treated. The objective of this study was to estimate the prevalence of harmful
      alcohol consumption (HAC) using various indicators and identify which groups of
      patients may require specific targeted interventions for HAC risk reduction. A
      cross-sectional survey, based on a random sample representative of people living
      with HIV/AIDS (PLWHA) was carried out in 102 French hospital departments
      delivering HIV care. As alcohol abuse is particularly detrimental to patients
      receiving highly active antiretroviral therapy (HAART), we focused only on those
      individuals receiving HAART with complete alcohol assessment (CAGE, AUDIT-C,
      regular binge drinking, N=2340). Collected information included medical and socio
      demographic data, HIV risk behaviors, adherence to treatment and substance and
      alcohol use, together with depression, anxiety, and experience of attempted
      suicide or sex work. HAC prevalence was evaluated as follows: 12% (CAGE score >
      or =2), 27% (AUDIT-C), and 9% (regular binge drinking). Three groups were at
      higher risk of HAC: men who have sex with men using stimulants, polydrug users,
      and to a lesser degree, ex-drug users. Innovative intervention strategies to
      reduce HAC and improve HIV prevention and HAART adherence in various PLWHA
      populations need urgent testing and implementation. Such interventions for
      alcohol risk reduction remain central to promoting improved HIV prevention and
      assuring HAART effectiveness in these populations.

PMID- 20824568
TI  - "Being faithful" in a sexual relationship: perceptions of Tanzanian adolescents
      in the context of HIV and pregnancy prevention.
AB  - Little is known about what adolescents think about faithfulness and partner
      reduction for HIV prevention (the "B" in the ABC HIV prevention behavior change
      strategy), including how they understand its implementation within relationships.
      In addition, because adolescents face the twin threats of HIV and unintended
      pregnancy, it is important to understand how adolescents may integrate their
      thinking on pregnancy prevention if they are using faithfulness or partner
      reduction as their HIV prevention strategy. This study gathered evidence by
      conducting 20 focus group discussions (FGDs) with 158 adolescents, aged 14-20.
      The FGDs were stratified by sex, age, current school attendance, rural or urban
      residence, and marital status. Results showed that the vast majority of groups
      felt that "B" messages are important and relevant for unmarried (as well as
      married) youth to hear for HIV prevention, but the messages need to be explicit
      (e.g., "being faithful means having only one tested sexual partner at a time").
      Faithful relationships are perceived as ideal in terms of romantic expectations
      and HIV prevention, but were considered unrealistic if the relationship had a
      power imbalance. Adolescents acknowledged the risks of multiple partners and a
      few recognized that concurrent partnerships are riskier than serial partnerships.
      Condoms were given as the primary method for pregnancy prevention among youth,
      yet faithfulness was usually seen as precluding condom use and many youth
      considered condom use as evidence of a lack of faithfulness. Overall, adolescents
      recognized that practicing fidelity is complex. Young people need life skills
      education for how to establish and maintain faithful relationships with one
      tested partner and how to integrate condom use for pregnancy prevention within
      that relationship. Programs also need to more explicitly address the issues of
      trust and repeat HIV testing within "faithful" relationships which is an
      uncomfortable but necessary reality for many adolescents.

PMID- 20824567
TI  - User fees and access to ARV treatment for persons living with HIV/AIDS:
      implementation and challenges in Burkina Faso, a limited-resource country.
AB  - Access to antiretroviral (ARV) treatment remains a crucial problem for patients
      living with HIV/AIDS (PLWHA) in limited-resources countries. Some African
      countries have adopted the principle of providing ARV free of charge, but Burkina
      Faso opted for a direct out-of-pocket payment at the point of care delivery, with
      subsidized payments and mechanisms for the poorest populations to receive these
      services free of charge. Our objectives were to determine the proportion of PLWHA
      who pay for ARV and to identify the factors associated with ARV access in Burkina
      Faso. A cross-sectional study was performed in 13 public health facilities, 10
      Nongovernmental Organizations and association health facilities, and three faith
      based health facilities. In each facility, 20 outpatients receiving ARV were
      interviewed during a routine clinic visit. A multivariate analysis by logistic
      regression was performed. Among the expected 520 patients receiving ARV, 499
      (96.0%) were surveyed. The majority of patients (79%) did not pay for their ARV
      treatment, thereby limiting cost recovery from patient payments. In a
      multivariate analysis, level of education and income were associated with free
      access to ARV. Patients with no education more frequently received free ARV than
      those who had received some level of education (OR 2.7, 95% CI [1.3-5.6]).
      Patients without any income or with less than US$10 per month were more likely to
      receive free ARV (OR 2.6 [95% CI 1.3-5.2]) than those who earned more than US$10
      per month. However, 16% of patients without any income and 21% of those without
      employment paid for ARV, and the costs of drugs for opportunistic infections,
      food, and transport remained a burden for 85%, 91%, and 74%, respectively, of
      those who did not pay for ARV. Free access to a minimum care package for every
      PLWHA would enhance access to ARV.

PMID- 20824569
TI  - Prevalence, correlates, and self-management of HIV-related depressive symptoms.
AB  - Depressive symptoms are highly prevalent yet undertreated in people living with
      HIV/AIDS (PLHAs). As part of a larger study of symptom self-management (N=1217),
      this study examined the prevalence, correlates, and characteristics (intensity,
      distress, and impact) of depressive symptoms, and the self-care strategies used
      to manage those symptoms in PLHAs in five countries. The proportion of
      respondents from each country in the total sample reporting depressive symptoms
      in the past week varied and included Colombia (44%), Norway (66%), Puerto Rico
      (57%), Taiwan (35%), and the USA (56%). Fifty-four percent (n=655) of the total
      sample reported experiencing depressive symptoms in the past week, with a mean of
      4.1 (SD 2.1) days of depression. Mean depression intensity 5.4 (SD 2.7),
      distressfulness 5.5 (SD 2.86), and impact 5.5 (SD 3.0) were rated on a 1-10
      scale. The mean Center for Epidemiologic Studies Depression Scale score for those
      reporting depressive symptoms was 27 (SD 11; range 3-58), and varied
      significantly by country. Respondents identified 19 self-care behaviors for
      depressive symptoms, which fell into six categories: complementary therapies,
      talking to others, distraction techniques, physical activity, medications, and
      denial/avoidant coping. The most frequently used strategies varied by country. In
      the US sample, 33% of the variance in depressive symptoms was predicted by the
      combination of education, HIV symptoms, psychological and social support, and
      perceived consequences of HIV disease.

PMID- 20824571
TI  - Booster biocides and microfouling.
AB  - Antifouling (AF) paints are used to prevent the attachment of living organisms to
      the submerged surfaces of ships, boats and aquatic structures, usually by the
      release of biocides. Apart from copper, organic booster biocides are the main
      active components in AF paints, but their use can have a negative impact on the
      marine environment. The direct effects of biocides on marine bacteria are poorly
      known. This work investigates the impact of two biocides, viz. diuron and
      tolylfluanid, on the growth and the viability of marine microorganisms and on
      their ability to form biofilms. The biocides in solution were found to inhibit
      growth of two strains of marine bacteria, viz. Pseudoalteromonas and Vibrio
      vulnificus, at a high concentration (1000 microg ml(-1)), but only a small effect
      on viability was observed. Confocal laser scanning microscopy (CLSM) showed that
      the booster biocides decreased biofilm formation by both bacteria. At a
      concentration of 10 microg ml(-1), the biocides inhibited cell attachment and
      reduced biofilm thickness on glass surfaces. The percentage of live cells in the
      biofilms was also reduced. The effect of the biocides on two diatoms, Fragilaria
      pinnata and Cylindrotheca closterium, was also evaluated in terms of growth rate,
      biomass, chlorophyll a content and attachment to glass. The results demonstrate
      that diuron and tolylfluanid are more active against diatoms than bacteria.

PMID- 20824572
TI  - Priming, recognition and autonomic discrimination in amnesia.
AB  - Six individuals with amnesia and matched healthy controls participated. There
      were two objectives. First, determine whether physiological activity at encoding
      relates to whether a word shows autonomic priming or is recognized. Second,
      propose a model for understanding relationships between recognition and autonomic
      priming. In amnesics, 'unrecognized' words were associated with better autonomic
      discrimination and lower levels of physiological activity at encoding. In healthy
      participants and amnesics, 'recognized' words were associated with poorer
      autonomic priming and higher levels of physiological activity at encoding. A
      state-dependent, activation-fractionation-inhibition model is proposed involving
      an orienting response elicited by preference and search and modulated by
      underlying memory strength.

PMID- 20824573
TI  - Sequelae of a left-sided parietal stroke: posterior alien hand syndrome.
AB  - Posterior alien hand syndrome is a new addition to a poorly understood group of
      movement disorders. Historically, anatomical lesions causing uncontrolled limb
      movement and a feeling of foreignness were found to be located in the corpus
      callosum or frontal lobe. Recent case reports, however, demonstrate the typical
      symptoms of alien hand syndrome with lesions located in the parietal/occipital
      lobes. Disturbance of normal function in these regions tends to produce less
      complex motor activity, such as hand levitation, along with a sensory component
      characterized by feeling of estrangement. We discuss a patient who presented with
      unusual symptoms following an outpatient procedure and was found to have
      posterior alien hand syndrome.

PMID- 20824574
TI  - Psychotherapists' response to borderline personality disorder: a core conflictual
      relationship theme analysis.
AB  - This study examined therapists' emotional and cognitive responses to patients
      with borderline personality disorder (BPD) versus patients with major depressive
      disorder (MDD). Therapists' narratives (N=80) were elicited using the
      Relationship Anecdotes Paradigm interview method and then scored according to the
      core conflictual relationship theme-Leipzig/Ulm method (CCRT-LU; Albani et al.,
      2002). The emotional valences of therapists' responses were significantly more
      negative toward patients with BPD. Therapists differentially experienced patients
      with BPD as typically withdrawing and patients with MDD as attending within
      sessions. Therapists felt less satisfied in their therapeutic role with BPD
      despite a consistent wish to help patients. Findings support the utility of the
      CCRT-LU method in investigating therapist relational experiences and underscore
      the challenges for BPD treatment.

PMID- 20824576
TI  - [Diagnosis of and therapy for non-muscle-invasive bladder cancer - state of the
      art].
AB  - Around 80 % of newly diagnosed bladder cancers are confined to the mucosa and
      staged as non-muscle-invasive bladder cancer (NMIBC) (Ta, T1, Cis). These tumours
      appear to segregate into different main molecular pathways with extremely
      variable prognoses. The standard treatment for NMIBC is transurethral tumour
      resection (TUR) with Re-TUR and adjuvant intravesical chemotherapy or
      intravesical immunotherapy in most cases. Several developments associated with
      diagnosis such as the usefulness of the new WHO grading classification, the
      benefit of photodynamic diagnosis (PDD) or narrow band imaging (NBI), as well as
      the clinical value of tumour markers are discussed. Therapy for NMIBC includes
      monopolar or bipolar TUR. Subsequent instillation therapy is given according to
      the risk stratification. Several promising new substances as well as device
      assisted procedures such as thermochemotherapy or EMDA are discussed. The
      additional information gained by PDD obviously leads to a better diagnosis and
      treatment of all NMIBC. Routine IVU does not seem necessary. The value of
      diagnostic urine tests is still insufficiently defined. Several new aspects
      concerning prognostic markers are presented. While early chemotherapy
      instillation seems sufficient in low-risk tumours and BCG is the standard
      treatment for high-risk disease, the literature about treatment of intermediate
      risk tumors is still conflicting. Especially problematic is the case of recurrent
      disease after intravesical therapy in intermediate and high-risk patients. The
      question as to what has to be done in failure after BCG is discussed. Cystectomy
      is a safe option but other approaches are potential alternatives.

PMID- 20824577
TI  - [A non-abscess-forming inflammation of the corpora cavernosa in a diabetic
      patient - case report].
AB  - An inflammation of the corpus cavernosum is relatively rare and must be
      differentiated from a tumour, abscess, thrombosis or embolism of the penile
      vessels. Most frequently inflammation of the corpus cavernosum is caused by
      iatrogenic interventions, followed by general infections and acute occlusion of
      penile vessels. Diabetes mellitus seems to be a predisposing factor. In the case
      of a 51-year-old diabetic patient with painful induration of the penis, an MR
      imaging study was undertaken to identify an inflammation of the corpora by
      exclusion of abscess formation. The inflammation responded well to a two-week
      oral Fluorchinolon treatment. Due to its high soft-tissue contrast, multiplanar
      layer images and, the MR scan was performed to identify an inflammation of the
      corpora cavernosa and to exclude an abscess formation. We consider a therapy with
      oral antibiotics to be sufficient for a non-abscess-forming cavernitis.

PMID- 20824578
TI  - [Laparoscopic adrenalectomy].

PMID- 20824579
TI  - "...and NOW we are going to look at the originals!".

PMID- 20824580
TI  - Aldo Ricardo Castaneda, MD, PhD: What is he really like?

PMID- 20824581
TI  - Richard van Praagh.

PMID- 20824582
TI  - Surgical management of congenital heart disease: correlation between hospital
      costs and the Aristotle complexity score.
AB  - BACKGROUND: Hospital costs are expected to correlate with clinical complexity. Do
      costs for congenital heart surgery correlate with Aristotle complexity scores?
      METHODS: 442 inpatient stays in 2008 were evaluated. Aristotle scores and levels
      were determined. Costs were estimated according to the German Institute for
      Hospital Reimbursement system. Pearson and Spearman R correlation coefficients
      and corresponding goodness-of-fit regression coefficients R2 were calculated.
      RESULTS: Mean basic and comprehensive Aristotle scores were 7.60 +/- 2.74 and
      9.23 +/- 2.94 points, respectively. Mean expenses per hospital stay amounted to
      29,369 +/- 30,823 Euros. Aristotle basic and comprehensive scores and levels were
      positively correlated with hospital costs. With a Spearman R of 1 and related R2
      of 0.9436, scores of the 6 Aristotle comprehensive levels correlated best. Mean
      hospital reimbursement was 26,412 +/- 17,962 Euros. Compensation was higher than
      expenses for patients in comprehensive levels 1 to 3, but much lower for those in
      levels 4 to 6. CONCLUSIONS: Aristotle comprehensive complexity scores were highly
      correlated with hospital costs. The Aristotle score could be used as a scale to
      establish the correct reimbursement after congenital heart surgery.

PMID- 20824583
TI  - Congenital heart surgery: applicability of hospital reimbursement according to
      German diagnosis-related groups system in conformity with the Aristotle
      complexity score.
AB  - BACKGROUND: Scores of Aristotle comprehensive complexity (ACC) levels have been
      demonstrated to correlate with the case-mix index (CMI) (cost-weights) generated
      by the German Diagnosis-Related Groups (DRG) 2009 version (G-DRG 2009). The
      equation used was "y = 0.5591 + 0.939 x" whereby y stands for cost-weight and x
      for ACC score. We hypothesised that each ACC level could be assigned a DRG (ACC
      DRG) and be used to determine hospital reimbursement. METHODS: 185 patients
      underwent cardiac surgery between January and June 2009. The ACC scores of these
      185 patients were grouped in ACC levels, based on the basic cost-weight value of
      their DRG. One ACC DRG was assigned to each group and a corresponding cost-weight
      calculated based on the aforementioned equation. The resulting ACC CMI was
      compared with the CMI generated by the G-DRG 2009 (G-DRG 2009 CMI). Finally, the
      ACC surgical performance (complexity x hospital survival) was used to calculate
      the cost-weight; the obtained CMI was called "effective ACC CMI". RESULTS: Mean
      ACC score was 9.515 +/- 3.611 points. Derived ACC CMI and related G-DRG 2009 CMI
      were 9.494 and 8.438, respectively. Hospital survival was 97.8 % (181/184).
      Therefore ACC surgical performance and "effective ACC CMI" were 9.306 and 9.297,
      respectively. For each ACC level, the number of patients (n), mean ACC score, ACC
      CMI and related G-DRG 2009 CMI were as follows: Level 1: n = 25, 4.024 +/- 0.879,
      4.338 and 5.911; Level 2: n = 30, 6.563 +/- 0.574, 6.722 and 6.602; Level 3: n =
      43, 8.665 +/- 0.540, 8.695 and 8.088; Level 4: n = 73, 11.730 +/- 1.690, 11.574
      and 9.612; Level 5: n = 14, 16.710 +/- 1.380, 16.249 and 11.843, respectively.
      CONCLUSIONS: The Aristotle score can be used to adjust hospital reimbursement by
      assigning a DRG and cost-weight value to each ACC level. Missing figures for
      level 6 can be obtained from a previous study which showed a mean score of 22.11
      +/- 1.24: the ACC CMI would be 21.320. The 6 ACC DRGs indicate the correct
      compensation based on the complexity of the procedure. Reimbursement using the
      German DRG 2009 appears to favour less complex cases, while procedures with a
      higher complexity are penalised. Reimbursement according to "effective ACC CMIs"
      would have a strong impact by supporting units providing high-quality care.

PMID- 20824584
TI  - Congenital heart surgery and Aristotle complexity score.

PMID- 20824585
TI  - The fate of the pulmonary autograft in the aortic position: experience and
      results of 98 patients in twelve years.
AB  - OBJECTIVE: The ideal prosthesis for aortic valve replacement in infants and
      adolescents is still controversially discussed. Implantation of mechanical
      prostheses or homografts is associated with serious risks such as reoperations,
      thromboembolic events and infections. This has led many surgeons to prefer the
      Ross operation. METHODS: Between 1996 and 2008 we performed Ross operations in 98
      children and infants with a mean age of 11 years (range 1 mo-25 y), including
      concomitant procedures (n = 33). The operation was performed as a full-root
      replacement in 97 and as a subcoronary implantation in one patient. The patients
      were followed for up to twelve years (follow-up complete) to determine clinical
      and echocardiographic parameters. Mean duration of follow-up was 60 +/- 37 (range
      3-150 months). RESULTS: Overall survival was 98 % (n = 96). In 70 patients (71.4
      %) no autograft insufficiency (AI) could be observed. AI grade I was present in
      22 patients (22.4 %), AI grade II in 3 patients (3 %), and AI grade III in one
      patient. The autograft in the latter patient was replaced by a mechanical
      prosthesis. Aortic root dilatation was observed in 10 patients (10.2 %). Z-score
      (median) in these patients was 4.1 (normal z-score < or = 2.4). One patient with
      aortic root dilatation was reoperated. A pacemaker was implanted in two patients.
      No patient is on constant anticoagulants. CONCLUSION: The anatomy and physiology
      of the LVOT is best restored by the implantation of a pulmonary autograft. This
      additionally provides a growth potential for infants at low risk for
      reoperations. Autograft dilatation is a risk that requires constant evaluation.

PMID- 20824586
TI  - Predictors for biventricular repair in pulmonary atresia with intact ventricular
      septum.
AB  - BACKGROUND: Pulmonary atresia with intact ventricular septum (PA-IVS) is a
      complex congenital heart defect with a large variety of right heart-sided
      morphologies. METHODS: We undertook a retrospective review of 86 patients with PA
      IVS with a special emphasis on the angiographic findings. The aim of the study
      was to determine predictors for biventricular repair. Initial surgical procedures
      depended on the right ventricular morphology, the tricuspid valve size and
      coronary anomalies. RESULTS: Fifty-five patients (64%) underwent decompression of
      the right ventricle (RV) as an initial procedure; 16 of them required an
      additional systemic-to-pulmonary artery shunt. Twenty-six patients (30%) had only
      a systemic-to-pulmonary artery shunt as their initial procedure. Five patients
      underwent interventional procedures performed by pediatric cardiologists.
      Biventricular repair was possible in 56 patients (65%). Univentricular palliation
      was achieved in 16 patients. Fourteen patients had only palliation with a
      systemic-to-pulmonary artery shunt. Mean tricuspid valve size was significantly
      bigger in patients with biventricular repair (z-score -3.6 +/- 2.6) than in
      patients who did not undergo biventricular repair (-5.2 +/- 1.7, P = 0.003).
      Predictors for biventricular repair were right ventricular decompression with or
      without systemic-to-pulmonary artery shunt ( P < 0.001), tripartite right
      ventricle ( P < 0.001) and the absence of coronary fistulae ( P < 0.001). Long
      term survival was 80% +/- 13% at 25 years for patients undergoing biventricular
      repair. CONCLUSIONS: Decompression of the RV as an initial surgical procedure
      improves the possibility of achieving biventricular repair with good long-term
      results. However, morphological factors such as right ventricular size and the
      absence of coronary fistulae are significant predictors for biventricular repair.

PMID- 20824587
TI  - Prognostic evaluation of nodal staging based on the new IASLC lymph node map for
      lung cancer.
AB  - BACKGROUND: The purpose of this study was to evaluate the new lymph node map
      proposed by the International Association for the Study of Lung Cancer (IASLC)
      from the point of prognosis, and to identify the significant prognostic factors
      in each pathological N stage. METHODS: We reviewed 647 consecutive patients with
      surgically resected non-small cell lung cancers. Survival was analyzed according
      to N stage and three prognostic subgroups: N1a (single N1 zone), N1b (multiple N1
      zones) or N2a (single N2 zone), and N2b (multiple N2 zones). The following
      prognostic factors were evaluated for each N stage: location of involved zones,
      number of involved lymph nodes, stations and zones, and the presence of skip
      metastases. RESULTS: (1) The survival curves showed a stepwise deterioration as
      the N stage increased. (2) No significant difference was observed in survival
      between the different locations of involved zones in each N stage. (3) In N2
      patients, the presence of skip metastases was a significant prognostic factor in
      multivariate analysis. CONCLUSIONS: The proposed IASLC map is valid for
      prognostic stratification. The prognostic impact of the presence of skip
      metastases on N2 disease should therefore be taken into consideration when
      carrying out the forthcoming revision of the TNM staging system.

PMID- 20824588
TI  - Carcinoembryonic antigen level in serum and pleural lavage fluid in non-small
      cell lung cancer.
AB  - BACKGROUND: This study evaluates the tumor marker index (TMI) based on
      carcinoembryonic antigen (CEA) levels in serum and pleural lavage fluid as a
      potential prognostic determinant for patients with non-small cell lung cancer
      (NSCLC). MATERIALS AND METHODS: Three hundred and eighty-three consecutive NSCLC
      patients were reviewed retrospectively. RESULTS: The 5-year survival of patients
      with normal and high serum CEA levels was 71.78% and 51.38%, respectively (P <
      0.0001). The 5-year survival of patients with high CEA levels in pleural lavage
      fluid was 25.0%, which was significantly poorer compared with that of patients
      with normal lavage CEA levels (78.23%, P < 0.0001). There was a 5-year survival
      rate of 73.75% in patients with a TMI less than or equal to 1.0 compared to a
      rate of only 55.12% in patients with a TMI greater than 1.0 (P < 0.001). Both
      univariate and multivariate analyses indicated the independent prognostic impact
      of the TMI. CONCLUSIONS: The TMI based on serum and lavage CEA levels might be
      useful for predicting the prognosis of NSCLC patients.

PMID- 20824589
TI  - Pulmonary sequestration: angioarchitecture evaluated by three-dimensional
      computed tomography angiography.
AB  - Pulmonary sequestration represents an anomaly of nonfunctioning tracheobronchial
      branching with retention of the embryonic systemic arterial supply. We report a
      case of intralobar pulmonary sequestration, in which the abnormal supplying
      artery and especially the abnormal draining vein were demonstrated by three
      dimensional computed tomography angiography and were confirmed and treated using
      a video-assisted thoracoscopic procedure.

PMID- 20824590
TI  - Respiratory distress after surgery of RVOT pathologies: a word of caution on
      pseudoaneurysm development.
AB  - Pseudoaneurysm of the right ventricle outflow tract (RVOT) is a rare complication
      in pediatric cardiac surgery. We report a patient who developed a right
      ventricular pseudoaneurysm 8 months after RVOT enlargement using a pericardial
      patch for infundibular pulmonary stenosis. Our patient was born with severe
      pulmonary valvular stenosis and treated with percutaneous balloon valvotomy in
      the neonatal period. Six months later, she developed infundibular pulmonary
      stenosis, which required surgical resection of right ventricle infundibular
      trabeculations and bovine pericardial patch enlargement. The postoperative period
      was normal. She was readmitted to hospital 5 months later complaining of
      wheezing, coughing and shortness of breath. Echocardiography showed a huge
      aneurysmal dilatation of the outflow patch in connection with the right
      ventricular cavity. The patient underwent resection of the pseudoaneurysm and
      former patch, followed by interposition of a bovine jugular vein conduit between
      the RVOT and pulmonary bifurcation. The early postoperative period was
      uncomplicated. On echocardiography, no significant residual gradient was measured
      through the conduit and there was no insufficiency of the valve. RVOT
      reconstruction with patch enlargement, homograft or conduit implantation can be
      the origin of pseudoaneurysms. Although their incidence is rare, they are often
      asymptomatic before becoming quite large and causing compression symptoms as in
      our patient with respiratory complaints due to airway compression. It is
      important to follow up these patients closely, especially in the first year after
      surgery since most aneurysms develop within 6 months of surgery.

PMID- 20824591
TI  - Internal mammary artery grafting for coronary hypoperfusion in children.
AB  - BACKGROUND: Pediatric coronary artery bypass is performed for ischemic
      complications of Kawasaki disease, congenital coronary anomalies, and iatrogenic
      pediatric coronary artery problems. METHODS: We performed myocardial
      revascularization using the internal mammary artery in 6 children. A review of
      outcomes is presented here. Patient ages ranged from 7 days to 10 years. RESULTS:
      There was no operative mortality. All coronary bypass grafts were patent at 3
      months to 3 years postoperatively. No patient had recurrent angina or showed
      signs of myocardial ischemia. CONCLUSION: Internal mammary artery bypass grafting
      can be successfully performed in infants and children with good results. Long
      term patency and growth of the anastomosis of the distal vessel are not clear,
      but good clinical and angiographic results have been reported even after 25
      years.

PMID- 20824592
TI  - Implantation of the FloWatch device and sepsis: remove or wait?
AB  - Although many reports describe the biological behavior of most prosthetic
      biomaterials in the presence of infection, little is known about the resistance
      of the FloWatch device to internal or external contamination. We report here on
      our experience with the FloWatch device in three pediatric patients who
      contracted persistent sepsis. Good control of infection and complete remission of
      sepsis were ultimately achieved in all three patients by intensive treatment with
      antibiotics without removal of the device.

PMID- 20824593
TI  - Right ventricular outflow obstruction of the patient with biventricular non
      compaction.
AB  - We present a case of a 16-year-old girl who underwent infundibular myectomy for
      right ventricular outflow tract obstruction complicated by biventricular non
      compaction. The pathogenesis of this condition remains unknown. In pediatric
      patients non-compaction cardiomyopathy is associated with other cardiac
      abnormalities and carries a high mortality as a result of heart failure. In view
      of her improved cardiac performance after operation, we believe that a cardiac
      repair procedure should be performed based on the usual indications if left
      ventricular function is preserved.

PMID- 20824594
TI  - Use of Contegra conduit reinforced with Goretex as a modified left Blalock
      Taussig shunt.
AB  - This is the first report of the construction of a modified Blalock-Taussig shunt
      using a Contegra conduit reinforced with Goretex in a 4-year-old boy. The patient
      had a complex cardiac history with a primary diagnosis of pulmonary atresia,
      hypoplastic right ventricle (RV) and RV-coronary artery fistula.

PMID- 20824595
TI  - Giant congenital coronary aneurysm of the left anterior descending artery.
AB  - Coronary artery aneurysms are uncommon, especially in young patients. Most
      aneurysms in young patients are congenital, traumatic or due to Kawasaki disease.
      Giant coronary aneurysms warrant surgical management due to their propensity for
      complications. Coronary artery bypass grafting (CABG) with suture closure of the
      involved coronary artery seems to be an appropriate management strategy. We
      describe a giant coronary artery aneurysm of the left descending coronary artery,
      15 x 18 cm in size, occurring in a 27-year-old male patient. This report
      underscores the need for further investigation to find the primary pathological
      defect causing giant coronary aneurysms, which often eludes us. Our experience
      suggests that this entity should be considered in the differential diagnosis of
      any young patient with chest pain.

PMID- 20824596
TI  - Interruption of the inferior vena cava and azygos continuation in a child with
      partial atrioventricular septal defect.
AB  - Congenital pathologies of the inferior vena cava are uncommon. Isolated
      congenital interruption of the inferior vena cava with azygos vein continuation
      could be considered part of the group of venous return anomalies. The major
      significance of this anomaly is its association with complex cardiac defects and
      the associated technical difficulties at the time of cardiac catheterization and
      abdominal surgery or interventional procedures. In our case, we describe a common
      atrium and partial atrioventricular septal defect in an 8-year-old girl with
      infrahepatic interruption of the inferior vena cava and azygos continuation
      without polysplenia. Magnetic resonance angiography and computed tomography,
      together with a clinical awareness of this pathology, can be used to diagnose
      this entity.

PMID- 20824597
TI  - A rare case of Gerbode defect associated with double orifice mitral valve.
AB  - Gerbode defect is an unusual cardiac defect; its association with a double
      orifice mitral valve has not been previously reported. We present a case of a 45
      year-old woman who complained of palpitation and dyspnea on exertion.
      Echocardiography revealed an abnormal communication between the left ventricle
      and the right atrium, but misinterpreted a double orifice mitral valve as fusion
      of the anterolateral commissure. The Gerbode defect was closed during
      cardiopulmonary bypass, while the double orifice mitral valve was left untouched.
      The patient was discharged 16 days postoperatively.

PMID- 20824598
TI  - Isolated congenital left ventricular diverticulum.
AB  - Isolated congenital left ventricular diverticulum is a rare malformation and
      fewer than 50 cases have been reported to date. We report here on a patient with
      the symptoms of atypical chest pain and distress, who had a successful surgical
      intervention for this malformation.

PMID- 20824599
TI  - [Antibiotic prescribing--who, where, what, how?].

PMID- 20824600
TI  - [Differences in antibiotic prescribing between general practitioners and
      pediatricians in Hesse, Germany].
AB  - BACKGROUND: A careful consideration of antibiotic prescription is necessary due
      to emerging antibiotic resistance. Differences in prescription rates between
      physician groups have only rarely been examined. We compared the prescription of
      antibiotics for systemic use in children between pediatricians and general
      practitioners (GPs). METHOD: Data source was the statutory health insurance
      sample AOK Hesse/KV Hesse. Overall, 47,033 insured children in 2006 between 2 and
      17 years of age were included in the analysis. Odds ratios (OR) and 95%
      confidence intervals (CI) for an antibiotic prescription were calculated by
      logistic regression adjusted for confounders, comparing pediatricians with GPs.
      Diagnosis-specific models were constructed. RESULTS: GPs and pediatricians
      prescribed 79.3% of all antibiotics in 2006 (40.6% and 38.7%, respectively).
      Significantly decreased ORs for an antibiotic prescription were observed for
      pediatricians, with OR (95% CI) of 0.46 (0.43-0.49), 0.40 (0.30-0.54) and 0.40
      (0.30-0.53) for respiratory tract infections, urinary tract infections and
      nonsuppurative otitis media, respectively. No significant associations were
      observed assessing scarlet fever, pneumonia and suppurative otitis media,
      respectively. CONCLUSION: In this retrospective analysis, pediatricians were
      associated with a lower antibiotic prescription rate regarding diagnoses where
      antibiotic therapy is not clearly indicated. However, in diagnoses where
      antibiotic therapy is clearly indicated, no differences in prescription rates
      between pediatricians and GPs were observed. Further studies are warranted to
      gain insight into different treatment strategies between different groups of
      medical practitioners.

PMID- 20824601
TI  - [A rare cause of thyreotoxicosis].
AB  - BACKGROUND: Amiodarone-induced thyrotoxicosis (AIT) should be included in
      differential diagnoses of thyrotoxicosis in presence of a suggestive drug
      history. Adequate treatment requires knowledge of the underlying type of AIT.
      HISTORY AND ADMISSION FINDINGS: A 68-year-old male was admitted because of
      progressive dyspnea and tachyarrhythmia. Symptoms of thyrotoxicosis, including
      agitation, sleep disturbances, and palpitations, had developed 14 days earlier
      and the patient's condition had worsened despite initiation of antithyroid
      treatment. INVESTIGATIONS: Laboratory values showed manifest hyperthyroidism.
      Thyroid autoantibodies proved negative. C-reactive protein and erythrocyte
      sedimentation rate were slightly increased. Ultrasound revealed a moderately
      increased thyroid without nodules and with normal perfusion. DIAGNOSIS, TREATMENT
      AND COURSE: Suspecting AIT type 2, treatment with high-dosed glucocorticoids and
      antithyroid drugs was initiated. Under additional beta-blockade and heart
      insufficiency therapy the patient's condition significantly improved. After
      achievement of euthyreosis, thyroidectomy was performed. CONCLUSIONS: In patients
      with preexisting thyroid disorders, such as Grave's disease or functional
      autonomy in multinodular goiter, the high iodine content of amiodarone may cause
      iodine-induced thyrotoxicosis, also known as AIT type I. Treatment comprises high
      dosed antithyroid drugs. In contrast, in patients suffering from AIT type II,
      toxic effects of amiodarone on a previously healthy thyroid result in destructive
      thyroiditis. Treatment consists of glucocorticoids in a dosage of 1 mg per kg
      body weight per day. Antithyroid treatment could be added in cases of equivocal
      diagnosis. In most cases, thyroidectomy is indicated. Whether amiodarone can be
      discontinued, should be discussed with the responsible cardiologist. Due to the
      long half-life time of amiodarone, treatment discontinuation will not result in
      an immediate improvement.

PMID- 20824602
TI  - [60-year-old patient with saddle nose deformity and Turkish saddle destruction].

PMID- 20824603
TI  - [Acute pulmonary embolism].
AB  - Acute pulmonary embolism (APE) presents with a broad clinical spectrum ranging
      from an even asymptomatic course to sudden cardiac death. Because APE is
      potentially life-threatening every suspicion of APE has to be clarified promptly
      by validated diagnostic algorithms. On the basis of the patients haemodynamic
      instability high-risk APE and non-high-risk APE is differentiated. Based on the
      presence of shock or hypotension every patient with suspicion of APE should
      promptly be stratified as high-risk APE or non-high-risk APE. There is a
      considerable difference in the diagnostic and therapeutic algorithms between high
      risk and non-high-risk APE. In suspicion of high-risk APE the patients require
      immediate diagnosis by multidetector CT or echocardiography and immediate
      recanalization of the occluded pulmonary arteries by thrombolysis or embolectomy.
      In haemodynamically stable patients sequential diagnostic workup and prompt
      therapeutic anticoagulation is recommended.

PMID- 20824604
TI  - [Doping, enhancement, betterment: tasks of tomorrow's medicine?].

PMID- 20824605
TI  - Glucosinolates profile of "mugnolo", a variety of Brassica oleracea L. native to
      southern Italy (Salento).
AB  - Glucosinolates (GLSs) from a variety of Brassica oleracea, known locally as
      "mugnolo" and widely distributed in southern Italy, were studied. It was found
      that "mugnolo" inflorescences are characterized by the presence of the aliphatic
      GLSs glucoraphanin (1.79 umol/g), glucoiberin, glucoerucin, and sinigrin, of the
      aromatic GLSs glucobarberin (0.56 umol/g) and gluconasturtin, and of the indole
      GLSs glucobrassicin (3.51 umol/g), neoglucobrassicin, 4-methoxyglucobrassicin,
      and 4-hydroxyglucobrassicin. Indole GLSs were predominant, while aliphatic and
      aromatic GLS were found in lower quantities. The metabolic profile of "mugnolo"
      leaves was also studied. It was found that 4-hydroxyglucobrassicin (0.13 umol/g)
      and glucoraphanin (0.11 umol/g) are the predominant GLSs. Vegetables of the
      Brassicaceae family are seldom consumed raw; therefore we also analyzed the GLS
      profile of "mugnolo" after cooking in water. The results showed variations in the
      GLSs content with a fall in concentration of 50%.

PMID- 20824606
TI  - Comment to the article: "Tubular diskectomy vs conventional microdiskectomy for
      sciatica: a randomized controlled trial".

PMID- 20824607
TI  - [Diagnosis of peripheral arterial occlusive disease].

PMID- 20824608
TI  - [What is your diagnosis? Multifocal aseptic osteonecrosis].

PMID- 20824609
TI  - [Delirium or behavioral and psychological symptoms of dementia in the elderly
      patient: diagnosis and treatment].
AB  - Acute confusional state, delirium, occurs in up to 80% of patients in the
      intensive care unit and is also a common, life-threatening and potentially
      preventable clinical syndrome among persons who are 65 years of age or older in
      general hospital. The cause of acute confusional state is typically
      multifactorial. Delirium and dementia are highly interrelated and dementia is the
      leading risk factor for delirium. So the key steps to distinguish between
      delirium and behavioural and psychological symptoms of dementia are to address
      all evident causes, e.g. dementia, dehydration, infection, polymedication and to
      prevent complications and treat behavioral symptoms. First nonpharmacologic
      approaches should be instituted, including a calm, comfortable environment with
      the use of orienting influences. Pharmacologic management should be reserved for
      patients whose symptoms would threaten their own safety or the safety of other
      persons. Therapeutic drug options include modern antidepressants and
      neuroleptics.

PMID- 20824610
TI  - ["Arteriosclerotic" aneurysm of the abdominal aorta].
AB  - We present a patient with an aortic aneurysm and the epidemiology, etiology,
      screening, symptoms and therapeutic options of abdominal aortic aneurysms are
      discussed. A widening of the abdominal aorta >3 cm is termed aortic aneurysm. As
      patients with aortic aneurysm are mostly oligosymptomatic until rupture occurs
      and an estimated 30,000 patients annually die from ruptured aortic aneurysm in
      the US a screening of the population at greatest risk (smokers, familial
      predisposition) is recommended. Screening is best done by ultrasound. Noninvasive
      therapy is limited to antiplatelet therapy and optimal adjustment of risk
      factors. For definitive treatment endovascular aortic repair (EVAR) is considered
      an established alternative to open surgery with lower 30 days mortality but
      higher reintervention rate.

PMID- 20824611
TI  - [Protein and creatine supplements and erroneous diagnosis of kidney diseases].

PMID- 20824612
TI  - [Check-up, what else?].
AB  - Evidence-based check-up does not only include medical history and physical
      examination but consultation with regard to recommended vaccinations, screening
      for cancer and cardiovascular risk factors. Patients with PAD are at high risk
      for cardiovascular events but frequently claudication is not mentioned during
      anamnesis, thus specific attention to exercise-dependent leg discomfort is
      necessary. Recognition of PAD related symptoms is important because it may
      implicate secondary cardiovascular prevention and specific therapeutic options
      including walking exercise and endovascular revascularisation exist.

PMID- 20824613
TI  - ["Good Morning, Doctor, I'm Flying to Australia Next Week!"].
AB  - Travel-related venous thromboembolism (VTE) is probably less frequent than
      previously suspected and becomes relevant when a flight lasts eight hours or
      more. Usually, general measures such as avoiding constrictive clothing or
      dehydration and doing gymnastics and walking around in the cabin are sufficient
      for preventing VTE. Compression stockings can be recommended when risk factors
      for VTE are present. Low molecular weight heparins in prophylactic dosage should
      be considered after previous VTE.

PMID- 20824614
TI  - [Not Available].

PMID- 20824615
TI  - [Not Available].

PMID- 20824619
TI  - Effects of lovastatin on the pharmacokinetics of nicardipine in rats.
AB  - It has been reported that both nicardipine and lovastatin are substrates of both
      the cytochrome P450 (CYP) 3A subfamily and P-glycoprotein (P-gp), and P-gp
      transport is unlikely to be a significant factor. Thus, the effects of oral
      lovastatin on the pharmacokinetics of intravenous and oral nicardipine were
      investigated in rats. Nicardipine was administered intravenously (4 mg/kg) and
      orally (12 mg/kg) with 0 (control), 0.3 and 1 mg/kg of oral lovastatin to rats.
      Lovastatin was administered 30 min before nicardipine administration. After
      intravenous administration of nicardipine with 0, 0.3 and 1  mg/kg of lovastatin,
      the total areas under the plasma concentration-time curve from time zero to
      infinity (AUCs) of nicardipine were not changed by lovastatin. However, after
      oral administration of nicardipine with 1 mg/kg of oral lovastatin, the AUC of
      nicardipine was significantly greater (by 67.4%), and the extent of absolute oral
      bioavailability (F) of nicardipine was increased (by 38.5%). The above data
      suggest that lovastatin did not considerably inhibit the metabolism of
      nicardipine via the hepatic CYP3A subfamily, but inhibited intestinal P-gp and/or
      the CYP3A subfamily.

PMID- 20824620
TI  - Autoimmunity in transfusion babesiosis: a spectrum of clinical presentations.
AB  - Transfusion-acquired babesiosis can be an asymptomatic or self-limited febrile
      hemolytic illness in a healthy host. A persistent, relapsing, and/or fulminant
      course with the development of life-threatening complications may be seen in
      immunocompromised or splenectomized patients. As in malaria, erythrocyte
      parasitemia is often associated with nonimmune hemolysis, and can be treated with
      erythrocytapheresis. Just as warm autoantibodies have been reported in malaria
      infection, the development of autoantibody-mediated immune hemolysis has been
      reported in babesiosis. We treated a previously healthy male with multiple
      injuries from a motor vehicle accident necessitating massive transfusion. Late in
      the hospitalization, his blood smear revealed Babesia microti, confirmed by PCR
      study and serology. This was eventually traced to a unit of blood from an
      asymptomatic blood donor that was transfused during his initial trauma care.
      Specific antibiotic therapy was begun, and severe hemolysis from a high parasite
      burden required red blood cell exchange which led to rapid abatement of the
      hemolysis. He had a positive DAT (IgG with a pan-reactive eluate) but no serum
      autoantibody. This persisted for 10 days following cessation of hemolysis, and
      became negative while still on antibiotics while his parasite burden became
      undetectable. Reports of autoimmunity associated with community acquired
      babesiosis often have severe hemolysis from their autoantibodies, but our case
      shows that autoantibodies may also follow transfusion-acquired babesiosis. The
      nature of the autoantigen is unknown.

PMID- 20824621
TI  - Effects of protein A immunoadsorption in patients with chronic dilated
      cardiomyopathy.
AB  - OBJECTIVES: The objective of this study was to investigate functional effects of
      immunoadsorption (IA) in patients with chronic nonfamilial dilated cardiomyopathy
      (DCM) regarding clinical and humoral markers of heart failure. BACKGROUND: IA has
      been shown to induce early hemodynamic improvement in patients with nonfamilial
      dilated cardiomyopathy (DCM). METHODS: We performed IA using protein A agarose
      columns on five consecutive days in 51 patients with chronic DCM, congestive
      heart failure of NYHA class >= II, left ventricular ejection fraction <=50%, and
      mean time since initial diagnosis of 5.0 +/- 5.8 years. RESULTS: Immediately
      after IA, immunoglobulin G (IgG) decreased by 89.4% and IgG3 by 66.7% (both P <
      0.0001). Median NT-pro BNP was reduced from 1230.0 ng L(-1) at baseline to 829.0
      ng L(-1) after 6 months (P < 0.0001). Also mean left ventricular ejection
      fraction (LVEF) was significantly improved (26.3% +/- 9.4% to 28.7% +/- 11.4%
      after 6 months, P = 0.016) and LVEF improved >=5% (absolute) in 21 of 51 (41.2%)
      patients. After 6 months, bicycle spiroergometry showed a significant increase in
      exercise capacity from 82.0 +/- 30.8 Watts to 93.1 +/- 34.3 Watts (P = 0.008)
      while VO2max rose from 15.0 +/- 4.1 to 16.4 +/- 4.8 mL min(-1) kg(-1) (P = 0.01).
      CONCLUSIONS: In this study, on heart failure patients with nonfamilial DCM, IA
      therapy significantly improved clinical and humoral markers of heart failure
      severity. These promising results may be due to the selected study population,
      with a shorter disease duration and the higher amount of IgG 3 reduction. Future
      blinded prospective multicenter studies are necessary to identify those patients
      that benefit most.

PMID- 20824622
TI  - Mononuclear cell collection in patients treated with extracorporeal
      photochemotherapy by using the off-line method: a comparison between COBE Spectra
      AutoPbsc version 6.1 and Amicus cell separators.
AB  - BACKGROUND: The first step (MNC collection) during extracorporeal
      photochemotherapy by using the off-line method is of paramount importance, since
      the product should be highly MNC-enriched with low RBC count to avoid UV-A
      intercepting by erythrocytes. MATERIAL AND METHODS: 10 patients (nine with
      chronic GvHD and one with bullous pemphigoid) underwent MNC collection on
      subsequent days either with the COBE Spectra AutoPbsc version 6.1 or the Amicus
      Crescendo cell separator. Total and differential WBC count were performed on
      peripheral blood samples before procedure and on the yields. The procedure
      parameters were recorded for comparison between the two devices. Analysis
      included descriptive statistics and paired t-test. RESULTS: No clinically
      relevant side effect with the exception of mild paresthesias was observed during
      the 20 MNC collections. Furthermore, no difference were observed as to pre
      collection hematological parameters. The mean total nucleated cell count in the
      yield was 6.99 +/- 2.39 * 10(9) with a MNC content of 5.9 +/- 2.19 * 10(9) in the
      Spectra group and 6.15 +/- 2.02 * 10(9) with 5.29 +/- 2.39 * 10(9) in the Amicus
      group (P = 0.407 and P = 0.540, respectively). PLT content was higher in the
      yield from the Spectra group when compared to the Amicus group (1.54 * 10(11) +/-
      0.74 vs. 0.53 * 10(11) +/- 0.34, P = 0.001). Moreover, no difference were
      observed in the RBC content in the product : 3.38 mL +/- 1.91 vs. 4.59 mL +/-
      2.09, P = 0.191, when COBE Spectra and Amicus were compared, respectively.
      CONCLUSIONS: Both devices provide a satisfactory MNC collection for further UV-A
      treatment.

PMID- 20824623
TI  - Use of various offset settings in the Fenwal Amicus during hematopoietic
      progenitor cell collection to increase lymphocyte yield and reduce cross-cellular
      contamination.
AB  - INTRODUCTION: Autologous HPC collection focus has been CD34+ cell yield but
      product content of other cells is important for patient survival, complications,
      and resource utilization. METHODS: Prospective, paired study examining MNC and
      RBC offsets (opens and closes collect valve, respectively) was performed using
      Fenwal Amicus. Lymphocyte, CD34+ cell yields, and cross-cellular contamination
      were compared using different MNC/RBC offsets and retrospective Spectra data.
      RESULTS: In paired comparisons, median lymphocyte yields were significantly
      different only between 0.0/7.0 (17.6 * 10(9)) and 1.5/5.0 (14.5 * 10(9)) offsets.
      CD34+ yields were not significantly different between offsets except 1.0/7.0 and
      1.5/5.0 (230.3 vs. 156.7 * 10(6)). Granulocytes, RBC, and PLT were significantly
      greater with higher RBC offset. Comparing all offsets, 1.5/5.0 collected fewer
      lymphocytes, granulocytes, RBC, and PLT. 1.5/6.0 offsets collected more
      lymphocytes than 1.5/5.0 but fewer granulocytes and RBC than others except
      1.5/5.0. For 1.5/6.0 offsets, PLT content was higher than 1.5/5.0, equivalent to
      the other offsets, and less than Spectra. CD34+ yields for 1.5/6.0 offsets were
      equivalent to others except 1.0/7.0. Manufacturer's default (2.3/6.8) collected
      equivalent lymphocytes and CD34+ to all offsets (except 1.0/7.0) and Spectra.
      Cross-cellular contamination was higher than 1.5/5.0 and 1.5/6.0 but equivalent
      to others with more RBC and fewer PLT than Spectra. CONCLUSION: For maximum
      lymphocyte yield and minimum contamination, 1.5/6.0 offsets appear optimal. For
      minimum lymphocyte yield and contamination, 1.5/5.0 offsets would be preferred.
      Manufacturer's default has CD34+ cell and lymphocyte yields similar to 1.5/6.0
      with greater contamination. Amicus can achieve lymphocyte and CD34+ yields
      similar to Spectra but has significantly less PLT removal.

PMID- 20824624
TI  - Teaching and learning apheresis medicine: The Bermuda Triangle in Education.
AB  - Apheresis Medicine has evolved markedly due to an explosion of knowledge and
      technology, whereas the time available for training has shrunk as curricula have
      become increasingly overloaded. Apheresis teaching has inherited a strong
      clinical context where real patient problems are used in a hands-on environment.
      To optimize instruction, those involved in the education of apheresis
      professionals need to have (1) knowledge of how clinical laboratory medicine
      education has developed as a field, (2) an understanding of what is known from
      theory and research about how people learn, and (3) the skills to design
      teaching/learning activities in ways consistent with literature-based principles
      of adult education. These developments in education provide a context for
      curriculum projects currently underway by the American Society for Apheresis.
      Teachers must determine which competencies are central to the essence of a
      trained professional. Specific, robust, learning objectives targeted toward the
      development of higher levels of thinking, professional attitudes, and requisite
      skills are formulated to guide the learner toward mastering those competencies.
      Curriculum is developed for each objective, consisting of content and the best
      teaching/learning methods to help learners attain the objective. Appropriate
      assessment strategies are identified to determine whether the objective is being
      achieved. The integration of objectives, curriculum, and assessment creates The
      Bermuda Triangle of Education (Richter, The Circle of Learning and Bermuda
      Triangle in Education, University of New Mexico School of Medicine, 2004). When
      educators do not effectively navigate The Bermuda Triangle of Education, learning
      may disappear into the murky depths of confusion and apathy. When successfully
      navigated, the result will be a significant learning experience that leads to
      transformation through education.

PMID- 20824625
TI  - Evidence-based selection criteria to protect blood donors.
AB  - A safe and adequate blood supply depends on healthy, volunteer blood donors.
      Blood centers have instituted various screening procedures in an effort to
      determine that donors are free of diseases that can be transmitted to patients by
      blood transfusion and are able to tolerate the collection procedure without
      experiencing significant complications. This review focuses on selection criteria
      intended to minimize the risk to the blood donor. Defining a rational, evidence
      based approach to donor selection is crucial not only to take reasonable
      precautions to protect the donors' health but also to eliminate practices that
      lead to the unnecessary deferral of large numbers of people without improving the
      safety of the donation process. Donor selection criteria, including predonation
      pulse and blood pressure, donor weight and total blood volume, minimum hemoglobin
      and donation interval, are considered against the available evidence that support
      or suggest the need to modify the current approach to protect blood donor health.

PMID- 20824626
TI  - Suicide in patients with pancreatic cancer.
AB  - BACKGROUND: Depression is highly prevalent in patients with pancreatic cancer and
      can result in fatal outcomes from suicides. The authors report suicide rates
      among patients with pancreatic cancer in the United States and identify factors
      associated with greater suicide rates. METHODS: The current study reviewed data
      in the SEER database for patients diagnosed with pancreatic adenocarcinoma from
      1995-2005. Logistic regression models were used to perform multivariate modeling
      for factors associated with suicide, while Kaplan-Meier analysis was used to
      assess factors affecting survival. RESULTS: Among 36,221 patients followed for
      22,145 person-years, the suicide rate was 135.4 per 100,000 person-years. The
      corresponding rate in the US population aged 65-74 years was 12.5 per 100,000
      person-years, with a Standardized Mortality Ratio (SMR) of 10.8 (95% CI, 9.2
      12.7). Greater suicide rates were noted in males (Odds Ratio (OR) 13.5 [95% CI,
      3.2-56.9, P < .001]) and, among males, in patients undergoing an operative
      intervention (OR 2.5 [95% CI, 1.0-6.5, P = .05]). Married men had a lesser risk
      of committing suicide (OR 0.3 [95% CI, 0.1-0.6, P = .002]). Median survival among
      patients undergoing operative intervention was 2 months for those who committed
      suicide compared with 10 months for those who did not commit suicide.
      CONCLUSIONS: Male patients with pancreatic adenocarcinoma have a risk of suicide
      nearly 11 times that of the general population. Patients who undergo an operative
      intervention are more likely to commit suicide, generally in the early
      postoperative period.

PMID- 20824627
TI  - Synthesis and comparative properties of two amide-generating resin linkers for
      use in solid phase peptide synthesis.
AB  - Well-characterized resins of high purity are critical for effective solid phase
      peptide synthesis (SPPS). The quality of commercial (4-methyl)benzhydrylamine
      resin (MBHA-resin), used for the synthesis of peptide amides, is not consistent
      and residual ketone functionalities are frequently present. Such ketone or
      aldehyde impurities lead to the formation of acylation-resistant deletion
      peptides in SPPS. To avoid these undesirable side reactions, we have optimized
      the preparation of two amide-generating linkers, which, in combination with
      aminomethyl-resin prepared directly from polystyrene resin, serve as alternatives
      to MBHA-resin for peptide amide synthesis. Then we have explored their
      comparative properties in SPPS. Use of sonication in reductive amination
      facilitated the synthesis of both benzhydrylamine (BHA) and MBHA linkers.

PMID- 20824628
TI  - Brain expression of Cre recombinase driven by pancreas-specific promoters.
AB  - Cre-loxP technology enables specific examination of the function and development
      of individual nuclei in the complex brain network. However, for most brain
      regions, the utilization of this technique has been hindered by the lack of mouse
      lines with Cre expression restricted to these regions. Here, we identified brain
      expressions of three transgenic Cre lines previously thought to be pancreas
      specific. Cre expression driven by the rat-insulin promoter (Rip-Cre) was found
      mainly in the arcuate nucleus, and to a lesser degree in other hypothalamic
      regions. Cre expression driven by the neurogenin 3 promoter (Ngn3-Cre mice) was
      found in the ventromedial hypothalamus. Cre expression driven by the pancreas
      duodenum homeobox 1 promoter (Pdx1-Cre) was found in several hypothalamic nuclei,
      the dorsal raphe and inferior olivary nuclei. Interestingly, Pdx1-Cre mediated
      deletion of vesicular GABA transporter led to postnatal growth retardation while
      Ngn3-Cre mediated deletion had no effects, suggesting a role for Pdx1-Cre
      neurons, but not pancreas, in the regulation of postnatal growth. These results
      demonstrate the potential for these Cre lines to study the function and
      development of brain neurons.

PMID- 20824629
TI  - Msx1 and Dlx5 function synergistically to regulate frontal bone development.
AB  - The Msx and Dlx families of homeobox proteins are important regulators for
      embryogenesis. Loss of Msx1 in mice results in multiple developmental defects
      including craniofacial malformations. Although Dlx5 is widely expressed during
      embryonic development, targeted null mutation of Dlx5 mainly affects the
      development of craniofacial bones. Msx1 and Dlx5 show overlapping expression
      patterns during frontal bone development. To investigate the functional
      significance of Msx1/Dlx5 interaction in regulating frontal bone development, we
      generated Msx1 and Dlx5 double null mutant mice. In Msx1(-/-) ;Dlx5(-/-) mice,
      the frontal bones defect was more severe than that of either Msx1(-/-) or Dlx5(-/
      ) mice. This aggravated frontal bone defect suggests that Msx1 and Dlx5 function
      synergistically to regulate osteogenesis. This synergistic effect of Msx1 and
      Dlx5 on the frontal bone represents a tissue specific mode of interaction of the
      Msx and Dlx genes. Furthermore, Dlx5 requires Msx1 for its expression in the
      context of frontal bone development. Our study shows that Msx1/Dlx5 interaction
      is crucial for osteogenic induction during frontal bone development.

PMID- 20824630
TI  - Time-resolved microscopy for imaging lanthanide luminescence in living cells.
AB  - Time-resolved luminescence (TRL) microscopy can image signals from lanthanide
      coordination complexes or other probes with long emission lifetimes, thereby
      eliminating short-lifetime (<100 ns) autofluorescence background from biological
      specimens. However, lanthanide complexes emit far fewer photons per unit time
      than conventional fluorescent probes, making it difficult to rapidly acquire high
      quality images at probe concentrations that are relevant to live cell
      experiments. This article describes the development and characterization of a TRL
      microscope that employs a light-emitting diode (LED, lambda(em) = 365 nm) for
      pulsed epi-illumination and an intensified charge-coupled device (ICCD) camera
      for gated, widefield detection. Europium chelate-impregnated microspheres were
      used to evaluate instrument performance in terms of short-lifetime fluorescence
      background rejection, photon collection efficiency, image contrast, and signal-to
      noise ratio (SNR). About 200 nm microspheres were imaged within the time
      resolution limit of the ICCD (66.7 ms) with complete autofluorescence
      suppression. About 40 nm microspheres containing ~400 chelate molecules were
      detected within ~1-s acquisition times. A luminescent terbium complex, Lumi4
      Tb(r), was introduced into the cytoplasm of cultured cells at an estimated
      concentration of 300 nM by the method of osmotic lysis of pinocytic vesicles.
      Time-resolved images of the living, terbium complex-loaded cells were acquired
      within acquisition times as short as 333 ms, and the effects of increased
      exposure time and frame summing on image contrast and SNR were evaluated. The
      performance analyses show that TRL microscopy is sufficiently sensitive and
      precise to allow high-resolution, quantitative imaging of lanthanide luminescence
      in living cells under physiologically relevant experimental conditions.

PMID- 20824631
TI  - Fc block treatment, dead cells exclusion, and cell aggregates discrimination
      concur to prevent phenotypical artifacts in the analysis of subpopulations of
      tumor-infiltrating CD11b(+) myelomonocytic cells.
AB  - It is well established that cancer cells can recruit CD11b(+) myeloid cells to
      promote tumor angiogenesis and tumor growth. Increasing interest has emerged on
      the identification of subpopulations of tumor-infiltrating CD11b(+) myeloid cells
      using flow cytometry techniques. In the literature, however, discrepancies exist
      on the phenotype of these cells (Coffelt et al., Am J Pathol 2010;176:1564-1576).
      Since flow cytometry analysis requires particular precautions for accurate sample
      preparation and trustable data acquisition, analysis, and interpretation, some
      discrepancies might be due to technical reasons rather than biological grounds.
      We used the syngenic orthotopic 4T1 mammary tumor model in immunocompetent BALB/c
      mice to analyze and compare the phenotype of CD11b(+) myeloid cells isolated from
      peripheral blood and from tumors, using six-color flow cytometry. We report here
      that the nonspecific antibody binding through Fc receptors, the presence of dead
      cells and cell doublets in tumor-derived samples concur to generate artifacts in
      the phenotype of tumor-infiltrating CD11b(+) subpopulations. We show that the
      heterogeneity of tumor-infiltrating CD11b(+) subpopulations analyzed without
      particular precautions was greatly reduced upon Fc block treatment, dead cells,
      and cell doublets exclusion. Phenotyping of tumor-infiltrating CD11b(+) cells was
      particularly sensitive to these parameters compared to circulating CD11b(+)
      cells. Taken together, our results identify Fc block treatment, dead cells, and
      cell doublets exclusion as simple but crucial steps for the proper analysis of
      tumor-infiltrating CD11b(+) cell populations.

PMID- 20824632
TI  - Tyramide signal amplification for analysis of kinase activity by intracellular
      flow cytometry.
AB  - Intracellular flow cytometry permits quantitation of diverse molecular targets at
      the single-cell level. However, limitations in detection sensitivity inherently
      restrict the method, sometimes resulting in the inability to measure proteins of
      very low abundance or to differentiate cells expressing subtly different protein
      concentrations. To improve these measurements, an enzymatic amplification
      approach called tyramide signal amplification (TSA) was optimized for assessment
      of intracellular kinase cascades. First, Pacific Blue, Pacific Orange, and Alexa
      Fluor 488 tyramide reporters were shown to exhibit low nonspecific binding in
      permeabilized cells. Next, the effects of antibody concentration, tyramide
      concentration, and reaction time on assay resolution were characterized. Use of
      optimized TSA resulted in a 10-fold or greater improvement in measurement
      resolution of endogenous Erk and Stat cell signaling pathways relative to
      standard, nonamplified detection. TSA also enhanced assay sensitivity and, in
      conjunction with fluorescent cell barcoding, improved assay performance according
      to a metric used to evaluate high-throughput drug screens. TSA was used to
      profile Stat1 phosphorylation in primary immune system cells, which revealed
      heterogeneity in various populations, including CD4+ FoxP3+ regulatory T cells.
      We anticipate the approach will be broadly applicable to intracellular flow
      cytometry assays with low signal-to-noise ratios.

PMID- 20824633
TI  - Transradial complex left main trifurcation intervention.
AB  - Trifurcation lesions, especially around the left main coronary artery (LMCA), are
      occasionally encountered. Complex lesions, involving the bifurcation or the
      trifurcation of the unprotected LMCA, represent a real challenge for
      interventional cardiologists. Trifurcation lesions intervention reported to have
      high overall major adverse cardiovascular events, and require the use of various
      complex interventional techniques, for example, large guiding catheters to
      accommodate three wires guiding simultaneously inflated balloons or stents. Here,
      we report a case of successful percutaneous coronary intervention supported by
      pre-and post-intravascular ultrasound imaging, on an LMCA trifurcation using a 6F
      guiding catheter via transradial approach. (c) 2010 Wiley-Liss, Inc.

PMID- 20824635
TI  - Taste disturbance following tonsillectomy--a prospective study.
AB  - OBJECTIVES/HYPOTHESIS: Persistent taste disturbance is a rare complication after
      tonsillectomy and mainly documented by case reports or a few retrospective and
      prospective trials with a limited number of patients. None could clarify
      frequency, time course, or prognosis of long-lasting dysgeusia after
      tonsillectomy. The aim of the study was to provide a symptom-based follow-up
      after tonsillectomy to assess postoperative taste disorders. STUDY DESIGN:
      Prospective clinical trial. METHODS: From December 2007 to June 2009 adult
      patients undergoing tonsillectomy were asked to take part in the trial. Two
      hundred twenty-three patients (119 female, 104 male; mean age, 33 +/- 13 years)
      were included. The day prior to surgery, and 2 weeks and 6 months after
      tonsillectomy a standardized questionnaire was completed by patients. The
      questionnaire focused on taste function, taste disorders, pain, foreign body
      sensation, and bleeding episodes after tonsillectomy. RESULTS: One hundred eighty
      eight (2 weeks) and 181 (6 months) patients returned the questionnaires. Thirty
      two percent (n = 60) of patients reported taste disorders after tonsillectomy 2
      weeks postoperatively and 15 patients (8%) at 6-month follow-up. Metallic and
      bitter parageusia were most frequently reported. The mean ratings of gustatory
      function were significantly lower 2 weeks after surgery (P < .001) and reached
      preoperative values 6 months after surgery. Almost 30% of patients reported
      postoperative bleeding, 10% long-lasting postoperative pain, and 20% foreign body
      sensation. CONCLUSIONS: Long-lasting taste disturbance (metallic and bitter
      parageusia) after tonsillectomy is more frequent than previously reported. Long
      lasting pain and foreign body sensation seem to be common symptoms. With regard
      to these results, a thorough preoperative explanation is mandatory.

PMID- 20824636
TI  - Histology of the healing tympanic membrane following perforation in rats.
AB  - OBJECTIVES/HYPOTHESIS: The aim of this study was to provide a detailed
      cytological account on the healing tympanic membrane (TM) over 14 days and to
      complement existing research into TM wound healing. STUDY DESIGN: The study is a
      prospective cohort study of 19 male Sprague-Dawley (Rattus norvegicus) rats.
      METHODS: Rat TMs were perforated using a sterile needle and sacrificed at time
      points during the 14 days following perforation. RESULTS: The healing of the TM
      resembles cutaneous wound healing except that the TM is unique in the lack of a
      supportive matrix beneath the regenerating epithelia. This prevents the influx of
      reparative cells and nutrients and the in growth of the usual fibroblastic
      reaction. CONCLUSIONS: TM wound healing contrasts with cutaneous wound healing in
      that keratinocytes are the first cells to close the wound and not the last. A
      keratin scaffold may not be important in the healing process. The malleus plays a
      crucial role in the healing of the TM and is the site of significant mitotic
      activity during the healing process. Migration across layers of the TM appears to
      account for the closure of the perforation.

PMID- 20824637
TI  - The clinical significance of nasal irrigation bottle contamination.
AB  - OBJECTIVES/HYPOTHESIS: This study aimed to assess the clinical relevance of
      contamination of nasal irrigation bottles in patients with recalcitrant chronic
      rhinosinusitis (CRS). Secondary investigations to identify the presence of
      bacterial biofilms on the inner surface of the bottles and to assess different
      sterilization methods were also undertaken. STUDY DESIGN: Prospective,
      observational. METHODS: Eleven patients with recalcitrant CRS who were already
      using nasal irrigation as part of their treatment regimen were examined every 2
      weeks for a period of 6 weeks. At each visit, a culture sample was taken from
      their irrigation bottle and middle meatus, and they were given a new irrigation
      bottle. Irrigation bottles from six patients were analyzed with scanning electron
      microscopy (SEM) to detect biofilm formation. Finally, new bottles were
      inoculated with different strains of Staphylococcus aureus and then cleaned with
      different methods. The bottles were cultured immediately after cleaning and 48
      hours later. RESULTS: Overall, 42 of 43 (97%) bottles collected demonstrated
      bacterial growth. Concurrent sinonasal and bottle infection with S. aureus was
      seen in 51% of patients during the study. Bacterial biofilms were demonstrated on
      the inner surface of four of the six irrigation bottles tested. Treatment with
      Milton's solution (1% NaOCl plus 19% NaCl) and microwaving were found to be
      effective methods for sterilizing the bottles both initially after the cleaning
      and 48 hours later. CONCLUSIONS: Patients who irrigate their nose and sinuses
      commonly contaminate their irrigation bottle, most often with S. aureus, which
      can be in the biofilm form. Simple cleaning methods could reduce contamination of
      the bottles.

PMID- 20824638
TI  - In reference to hereditary hemorrhagic telangiectasia/avastin.

PMID- 20824640
TI  - Quantitative laryngeal electromyography: turns and amplitude analysis.
AB  - OBJECTIVES: Laryngeal electromyography (LEMG) is primarily a qualitative
      examination, with no standardized approach to interpretation. The objectives of
      our study were to establish quantitative norms for motor unit recruitment in
      controls and to compare with interference pattern analysis in patients with
      unilateral vocal fold paralysis (VFP). DESIGN: Retrospective case-control study
      METHODS: We performed LEMG of the thyroarytenoid-lateral cricoarytenoid muscle
      complex (TA-LCA) in 21 controls and 16 patients with unilateral VFP. Our
      standardized protocol used a concentric needle electrode with subjects performing
      variable force TA-LCA contraction. To quantify the interference pattern density,
      we measured turns and mean amplitude per turn for >=10 epochs (each 500
      milliseconds). Logarithmic regression analysis between amplitude and turns was
      used to calculate slope and intercept. Standard deviation was calculated to
      further define the confidence interval, enabling generation of a linear-scale
      graphical "cloud" of activity containing >=90% of data points for controls and
      patients. RESULTS: Median age of controls and patients was similar (50.7 vs. 48.5
      years). In controls, TA-LCA amplitude with variable contraction ranged from 145
      1112 MUV, and regression analysis comparing mean amplitude per turn to root-mean
      square amplitude demonstrated high correlation (R = 0.82). In controls performing
      variable contraction, median turns per second was significantly higher compared
      to patients (450 vs. 290, P = .002). CONCLUSIONS: We first present interference
      pattern analysis in the TA-LCA in healthy adults and patients with unilateral
      VFP. Our findings indicate that motor unit recruitment can be quantitatively
      measured within the TA-LCA. Additionally, patients with unilateral VFP had
      significantly reduced turns when compared with controls.

PMID- 20824639
TI  - Comparison of gentamicin distribution in the inner ear following administration
      via the endolymphatic sac or round window.
AB  - OBJECTIVE/HYPOTHESIS: The distribution of gentamicin in the inner ear via the
      endolymphatic sac (ES) or round window (RW) routes was investigated. STUDY
      DESIGN: Experimental study. METHODS: A fluorescent gentamicin-Texas Red conjugate
      (GTTR) was adopted to visualize the gentamicin. Adult guinea pigs were treated
      with GTTR applied to the ES or RW, the animals were allowed to recover for 3
      days, then confocal microscopy was used to observe and quantify GTTR
      distributions in cochlear and vestibular sensory epithelium. RESULTS: When GTTR
      was applied via the ES, strong GTTR labeling was observed in the vestibule while
      little GTTR was detected in the cochlea (P < .0001). However, distinct GTTR
      fluorescence was observed in the cochlea and vestibule following RW application
      (P = .7967). There was less GTTR labeling in cochlea via ES application than
      through RW administration (P < .0001). CONCLUSIONS: ES drug application may be
      preferable for the treatment of intractable Meniere's disease. Laryngoscope,
      2010.

PMID- 20824641
TI  - The impact of radiotherapy on facial nerve repair.
AB  - OBJECTIVE: To study the impact of radiotherapy on the success of primary facial
      nerve repair and cable nerve grafts. STUDY DESIGN: Retrospective review. METHODS:
      Pre- and postoperative facial nerve function were assessed using the House
      Brackmann (HB) grading system. RESULTS: Thirty-nine patients were identified who
      had undergone facial nerve repair: 5 patients (13%) underwent primary repair, and
      34 patients (87%) underwent nerve grafting. Radiotherapy was administered
      postoperatively to 34 patients (87%). Preoperative HB scores were I = 18, II =
      11, III = 3, IV = 3, V = 3, and VI = 1. Postoperative scores were HB I = 1, II =
      4, III = 16, IV = 6, V = 3, and VI = 9. Only patients with single-branch deficits
      recovered to HB I or II function. Good facial function (HB I-III) was achieved in
      17 of 34 patients (50%) who received postoperative radiotherapy compared to 4 of
      5 patients (80%) who did not receive postoperative radiotherapy (P = .349). Among
      the patients who had either HB I or II function preoperatively, 59% achieved good
      postoperative function (HB I-III). Four out of 10 patients (40%) with
      significantly compromised preoperative facial function (HB III-VI) were able to
      achieve HB III function. CONCLUSIONS: Postoperative radiotherapy appears not to
      prevent achieving good facial function after a nerve repair, especially when
      normal or near-normal function is present preoperatively. Some patients with fair
      to little function preoperatively can achieve reasonable postoperative function
      with facial nerve reconstruction.

PMID- 20824642
TI  - Automated high-level disinfection of nonchanneled flexible endoscopes: duty
      cycles and endoscope repair.
AB  - PURPOSE: Guidelines issued by the Association of Operating Room Nurses and the
      Association of Professionals in Infection Control and Epidemiology recommend high
      level disinfection (HLD) for semicritical instruments, such as flexible
      endoscopes. We aim to examine the durability of endoscopes to continued use and
      automated HLD. We report the number of duty cycles a flexible endoscope can
      withstand before repairs should be anticipated. METHODS: Retrospective review.
      RESULTS: A total of 4,336 endoscopic exams and subsequent disinfection cycles
      were performed with 60 flexible endoscopes in an outpatient tertiary pediatric
      otolaryngology practice from 2005 to 2009. All endoscopes were systemically
      cleaned with mechanical cleansing followed by leak testing, enzymatic cleaning,
      and exposure to Orthophthaldehyde (0.55%) for 5 minutes at a temperature of at
      least 25 degrees C, followed by rinsing for 3 minutes. A total of 77 repairs were
      performed, 48 major (average cost $3,815.97), and 29 minor (average cost
      $326.85). On average, the 2.2-mm flexible endoscopes were utilized for 61.9
      examinations before major repair was needed, whereas the 3.6 mm endoscopes were
      utilized for 154.5 exams before needing minor repairs. No major repairs have been
      needed to date on the 3.6-mm endoscopes. CONCLUSIONS: Automated endoscope
      reprocessor use for HLD is an effective means to disinfect and process flexible
      endoscopes. This minimizes variability in the processing of the endoscopes and
      maximizes the rate of successful HLD. Even when utilizing standardized, automated
      HLD and limiting the number of personnel processing the endoscopes, smaller
      fiberoptic endoscopes demonstrate a shortened time interval between repairs than
      that seen with the larger endoscopes. Laryngoscope, 2010.

PMID- 20824643
TI  - Pedicled facial buccinator (FAB) flap: a new flap for reconstruction of skull
      base defects.
AB  - BACKGROUND: The expansion of endoscopic endonasal skull base surgery has resulted
      in an increased demand for reconstructive options. Reconstruction with
      vascularized tissue has proven indispensable for reliably separating the cranial
      contents from the paranasal sinuses following extended endoscopic endonasal
      approaches (EEA). The introduction of the Hadad-Bassagasteguy flap (vascular
      pedicle nasoseptal flap, HBF) at our institution decreased our postoperative
      cerebral spinal fluid (CSF) leak rates from more than 20% to less than 5%. The
      HBF is not always available, as the nasoseptal area or its vascular supply can be
      compromised by tumor or prior surgery. In an attempt to keep pace with rapidly
      expanding reconstructive requirements, we present the anatomic and cadaveric
      foundations for novel modifications of the facial artery musculo (-mucosal)
      (FAM[M]) and buccinator flaps to allow vascularized reconstruction of the skull
      base. STUDY DESIGN: Feasibility. Cadaveric study. METHODS: Using cadaver
      dissections and measurements, we investigated the feasibility of transposing
      pedicled buccinator myo/myomucosal flaps into the nasal cavity and skull base.
      Both muscular and myomuscular flaps were raised, and techniques for transposition
      into the nasal cavity were investigated. Three fresh and six preserved human
      specimens were dissected. RESULTS: Pedicled facial buccinator flaps with and
      without mucosa were transposed into the nasal cavity using a variety of maxillary
      osteotomies. No facial incisions were required. It was demonstrated that the
      flaps reach the anterior skull base and planum sphenoidale. CONCLUSIONS: The
      transposition of pedicled buccinator muscle flaps with and without mucosa into
      the nasal cavity could reach the anterior skull base and planum sphenoidale, if
      the appropriate surgical technique is used. The pedicled Facial Buccinator Flap
      holds significant potential as a reconstructive alternative for a variety of
      skull base defects, alone or in combination with existing reconstructive options.
      2010.

PMID- 20824644
TI  - N-acetylcysteine counteracts oxidative stress and prevents hCG-induced apoptosis
      in rat Leydig cells through down regulation of caspase-8 and JNK.
AB  - We have earlier reported that following persistent stimulation with hCG,
      oxidative stress-induced apoptosis in rat Leydig cells was mainly achieved
      through the extrinsic pathway. In the present study, the role of N-acetylcysteine
      (NAC) in counteracting the oxidative stress and the mechanisms of inhibition of
      apoptosis under such conditions were investigated. NAC (1 mM) intervention with
      repeated hCG stimulation (50 ng/ml, four times, each with 30 min challenge)
      prevented the decline in Leydig cell viability and the rise in lipid peroxidation
      and reactive oxygen species. Simultaneously, the activities of the enzymes
      glutathione-S-transferase, catalase, superoxide dismutase and the intracellular
      glutathione and antioxidant capacity of the treated cells improved significantly.
      Apoptotic markers Fas, FasL, and caspase-8, up-regulated following repeated hCG
      exposure, were significantly down-regulated following NAC co-incubation. While
      Bcl-2 expression was fully restored, Bax and caspase-9 remained unchanged. NAC
      treatment induced down-regulation of upstream JNK/pJNK and down-stream caspase-3
      in the target cells. Taken together, the above findings indicate that NAC
      counteracted the oxidative stress in Leydig cells induced as a result of repeated
      hCG stimulation, and inhibited apoptosis by mainly regulating the extrinsic and
      JNK pathways of metazoan apoptosis.

PMID- 20824645
TI  - Deformation of nasal septum during nasal trauma.
AB  - BACKGROUND: Injury to the nasal septum is commonly found in most nasal fractures.
      The nasal septum deforms and crumples, leading to nasal deviation and internal
      nasal obstruction. AIM: This study aims to identify the main areas of high stress
      concentration when a dynamic anteroposterior load is applied to the nasal tip,
      simulating nasal trauma. We wish to determine if the nasal septum acts as a
      crumpled zone, and deforms significantly during nasal trauma. MATERIALS AND
      METHODS: An idealized and a patient-specified finite element model have been
      generated for the present study. Several models with various combinations of
      narrower angle at the Vomer Ethmoidal Junction (VEJ) are also constructed from
      this septum model. Finite element analyses are carried out to determine the
      deformation and stress distribution in the nasal septum when a dynamic
      anteroposterior load is applied to the nasal tip. CONCLUSIONS: The maximum stress
      areas in the nasal septum are in the vicinity of the bony-cartilaginous (BC)
      junction and the anterior nasal spine (ANS), which are consistent with clinical
      experience. A larger anteroposterior load, a longer loading duration, and a more
      acute VEJ angle would result in higher maximum stresses. The observations were
      identical in both idealized and patient-specific models. The findings of this
      analysis also suggest that the septum does function as a crumpled zone, absorbing
      a significant amount of stress before it is transmitted to the skull.

PMID- 20824646
TI  - Excision of congenital nasolacrimal duct cyst with powered instrumentation.

PMID- 20824647
TI  - The effect of surface topography on early NFkappaB signaling in macrophages.
AB  - Surface topography modulates macrophage expression of pro-inflammatory cytokines
      through triggering of a number of different signaling pathways. In this article,
      we investigated the early activation of the NFkappaB pathway in RAW 264.7
      macrophages in response to four surface topographies: mechanically polished (PO),
      coarse sand blasted (CB), acid etched (AE), and sandblasted and acid etched
      (SLA). We found that activation of the NFkappaB pathway was topography dependent.
      The PO and CB surfaces showed the highest level of activation, followed by the
      AE, then the SLA. Addition of suboptimal stimulatory concentrations of
      lipopolysaccharide (LPS) enhanced the response. Second, we determined that
      topography dependent cell signaling occurred in the absence of fetal bovine sera
      in the media. Third, we demonstrated that disruption of the lipid rafts by
      removal of cholesterol from cells in suspension using methyl beta cyclodextrin
      (MbetaCD) affected signaling through the NFkappaB pathway and transcription of
      the pro-inflammatory cytokine IL-1 beta, but did not affect cell adhesion,
      spreading or morphology. The number of macrophages adhered to the surfaces after
      30 min followed the order PO, CB, AE, and SLA. In conclusion, our study suggests
      that one mechanism by which surface topography modulates activation of the
      NFkappaB pathway is through cholesterol-enriched raft-associated
      adhesive/signaling structures.

PMID- 20824648
TI  - Electrospun cross-linked gelatin fibers with controlled diameter: the effect of
      matrix stiffness on proliferative and biosynthetic activity of chondrocytes
      cultured in vitro.
AB  - Nanofibrous scaffolds were prepared from gelatin solutions and were further cross
      linked with glutaraldehyde (GA). The fiber diameter was varied from 100 to 1000
      nm by controlling the applied voltage (4-15 kV) and the concentration of the
      gelatin solution (4-15%). The tensile moduli and the tensile strength of the
      noncross-linked scaffolds varied from 20 to 120 MPa and 0.5 to 3.5 MPa,
      respectively. Cross-linking with GA led to an increase in both the tensile
      modulus and strength and correlated with cross-linker concentration. Gelatin
      based matrices were characterized by Fourier transform infrared spectroscopy and
      differential scanning calorimetry. High cellular viabilities and rounded
      morphology of chondrocytes was observed at the end of 7 days in culture with
      added matrix deposition and flattening of cells at 15 days. Matrix stiffness was
      noted to impact cell densities and the expression of chondrocytic markers,
      especially aggrecan. The ratios of collagen-II (C-II) to collagen-I (C-I) of 0.62
      and 1.33 were noted on gelatin nanofibrous scaffolds cross-linked with 0.1% GA at
      the end of 7 and 15 days in culture, respectively. C-II/C-I ratios of 1.30 and
      2.58 were noted on scaffolds cross-linked with 1.0% GA at the end of 7 and 15
      days in culture, respectively.

PMID- 20824649
TI  - Genipin-crosslinked silk fibroin/hydroxybutyl chitosan nanofibrous scaffolds for
      tissue-engineering application.
AB  - To improve water-resistant ability and mechanical properties of silk fibroin
      (SF)/hydroxybutyl chitosan (HBC) nanofibrous scaffolds for tissue-engineering
      applications, genipin, glutaraldehyde (GTA), and ethanol were used to crosslink
      electrospun nanofibers, respectively. The mechanical properties of nanofibrous
      scaffolds were obviously improved after 24 h of crosslinking with genipin and
      were superior to those crosslinked with GTA and ethanol for 24 h. SEM indicated
      that crosslinked nanofibers with genipin and GTA vapor had good water-resistant
      ability. Characterization of the microstructure (porosity and pore structure)
      demonstrated crosslinked nanofibrous scaffolds with genipin and GTA vapor had
      lager porosities and mean diameters than those with ethanol. Characterization of
      FTIR-ATR and (13)C NMR clarified both genipin and GTA acted as crosslinking
      agents for SF and HBC. Furthermore, genipin could induce SF conformation from
      random coil or alpha-helix to beta-sheet. Although GTA could also successfully
      crosslink SF/HBC nanofibrous scaffolds, in long run, genipin maybe a better
      method due to lower cytotoxicity than GTA. Cell viability studies and wound
      healing test in rats clarified that the genipin-crosslinked SF/HBC nanofibrous
      scaffolds had a good biocompatibility both in vitro and in vivo. These results
      suggested that genipin-crosslinked SF/HBC nanofibrous scaffolds might be
      potential candidates for wound dressing and tissue-engineering scaffolds.

PMID- 20824650
TI  - Long-bone critical-size defects treated with tissue-engineered polycaprolactone
      co-lactide scaffolds: a pilot study on rats.
AB  - The aim of this study was to evaluate the osteogenic potential of embroidered,
      tissue-engineered polycaprolactone-co-lactide (trade name: PCL) scaffolds for the
      reconstruction of large bone defects. Ten piled-up PCL scaffolds were implanted
      in femura with a critical size defect of immunodeficient nude rats for 12 weeks
      [n = 4, group 1: noncoated, group 2: collagen I (coll I), group 3: collagen
      I/chondroitin sulfate (coll I/CS), and group 4: collagen I/chondroitin
      sulfate/human mesenchymal stem cells (coll I/CS/hMSC)]. X-ray examination,
      computer tomography, and histological analyses of the explanted scaffold pads
      were performed. The quantification of the bone volume ratio showed a
      significantly higher rate of new bone formation at coll I/CS-coated scaffolds
      compared with the other groups. Histological investigations revealed that the
      defect reconstruction started from the peripheral bone ends and incorporated into
      the scaffold material. Additionally seeded hMSC on coll I/CS-coated scaffolds
      showed a higher matrix deposition inside the implant but no higher bone formation
      was observed. These data imply that the coll I/CS-coated PCL scaffolds have the
      highest potential for treating critical size defects. The scaffolds, being
      variable in size and structure, can be adapted to any bone defect.

PMID- 20824651
TI  - An in vitro study of plasticized poly(lactic-co-glycolic acid) films as possible
      guided tissue regeneration membranes: material properties and drug release
      kinetics.
AB  - Guided tissue regeneration (GTR), in periodontal therapy, involves the placement
      of a barrier membrane, to ensure the detached root surface becomes repopulated
      with periodontal ligament cells capable of regenerating this attachment. GTR
      procedures exhibit large variability in surgical outcome as a consequence of poor
      membrane performance. The objective of this study was to evaluate the suitability
      of plasticized poly(lactic-co-glycolic acid) (PLGA) as a material for GTR
      membranes. The material was also investigated as a localized controlled release
      system for the antibiotic, anti-inflammatory agent tetracycline. Films made from
      PLGA (85:15), plasticized with either 10% w/v methoxypoly(ethyleneglycol) (MePEG)
      or a diblock copolymer [poly(D,L-lactic acid)-block-methoxypoly(ethyleneglycol)]
      were loaded with tetracycline base (or hydrochloride salt) and cast by solvent
      evaporation. Drug release was measured using high performance liquid
      chromatography (HPLC). The time-course of elasticity changes and swelling were
      determined using a stress-strain apparatus or gravimetric/dimensional
      determinations, respectively. Cells extracted from periodontal ligament cell
      explants were used to evaluate the effect of material and drug loading on cell
      morphology. Tetracycline.HCl released more rapidly than tetracycline from PLGA
      films. The addition of either MePEG or diblock caused a concentration dependent
      increase in release rates for both drugs. Release profiles ranged from a small
      initial burst phase followed by slow sustained release to almost full drug
      release after 1 day. After incubation in PBS, the films stiffened and swelled
      within 30 min. Periodontal ligament cell morphology was not affected by the
      inclusion of tetracycline. Plasticized PLGA films displayed desired features for
      possible use as GTR membranes.

PMID- 20824653
TI  - The effect of the Psychopathy Checklist--Revised in capital cases: mock jurors'
      responses to the label of psychopathy.
AB  - Despite mixed empirical evidence regarding the ability of the Psychopathy
      Checklist - Revised (PCL-R) to predict violence among incarcerated inmates, it
      continues to be used to address such questions, even in the context of capital
      cases. The purpose of this study was to examine if the PCL-R has a prejudicial
      effect on mock jury members during the sentencing phase of a capital murder
      trial. Results indicated that participants were more likely to sentence the
      defendant to death when the defendant exhibited a high likelihood to commit
      future violence, whether or not the diagnostic label "psychopath" was present.
      Interestingly, when asked to rate the defendant's likelihood for future violence
      and murder, the defendant who was a high risk for future violence and not labeled
      a psychopath received the highest rating. These results suggest an absence of
      juror bias as it pertains to the label "psychopath" when sentencing a defendant
      in a capital murder case.

PMID- 20824654
TI  - Expression of glucocorticoid receptor spliced variants in lymphoma cell lines.

PMID- 20824655
TI  - Xenobiotic and folate pathway gene polymorphisms and risk of childhood acute
      lymphoblastic leukaemia in Javanese children.
AB  - Xenobiotic and folate metabolic pathways are important for the maintenance of
      genetic stability and may influence susceptibility to the development of
      childhood acute lymphoblastic leukaemia (ALL). In this study, we investigated 10
      polymorphisms in 6 genes (GSTM1-present/null, GSTT1-present/null, GSTP1 1578A >
      G, NQO1 609C > T, MTHFR 677C > T, MTHFR 1298A > C, MTHFD1 1958G > A, 3'-TYMS 1494
      6bp-deletion/insertion, 5'-TYMS 28bp-tandem repeats, and SLC19A1 80G > A) in a
      cohort of 185 Javanese children with ALL and 177 healthy controls. In ALL
      patients, none of the polymorphisms demonstrated a statistically significant
      association with ALL after correcting for multiple comparisons. Gender-stratified
      analysis showed that in girls, GSTT1-null genotype was associated with increased
      ALL risk (OR = 2.20; p = 0.027), while GSTP1 1578AG genotype was associated with
      reduced risk (OR = 0.43; p = 0.031). Strong linkage disequilibrium between the
      MTHFR 677C > T and 1298A > C polymorphisms was observed (D' = 1.0; r(2) = 0.072).
      The haplotypes 677C-1298C and 677T-1298A were associated with a reduced risk of
      ALL (OR = 0.68 and 0.64, respectively; gender-adjusted global p = 0.028).
      Classification and regression tree (CART) analysis was employed to identify
      potential high-order gene-gene interactions and cluster subjects into
      susceptibility groups. SLC19A1 80G > A emerged as the predominant polymorphism
      associated with risk of ALL. Individuals simultaneously carrying MTHFR 1298AA, 3'
      TYMS 6bp deletion(s) and SLC19A1 80A-allele(s) were at higher disease risk (OR =
      2.21; p < 0.001). On the contrary, simultaneous possession of MTHFR 1298CC, 3'
      TYMS 6bp homozygosity and SLC19A1 80A-allele(s) conferred lower risk (OR = 0.25;
      p = 0.004). Carriage of NQO1 609C-allele amongst SLC19A1 80GG genotype was
      associated with lower risk (OR = 0.47; p = 0.003). In conclusion, our study has
      demonstrated the importance of gender and gene-gene interaction within the
      xenobiotic and folate pathways in modulating childhood ALL susceptibility.

PMID- 20824656
TI  - A look inside the framework: EU funding priorities and criteria in the health
      theme of the co-operation programme.

PMID- 20824658
TI  - Preparation and characterization of molecularly imprinted silica monolith for
      screening sulfamethazine.
AB  - In this work, a novel approach of preparing molecularly imprinted film
      derivatized silica monolith materials was developed by a two-step procedure. The
      silica monolithic support was first prepared by the sol-gel method with
      tetramethoxysilane as the precursor. Subsequently, vinyl groups were introduced
      onto the surface of silica monolith by immobilization of gamma
      methacryloxypropyltrimethoxysilane. The prepolymerization mixtures, consisting of
      methacrylic acid as a functional monomer, ethylene dimethacrylate as a
      crosslinker, sulfamethazine as a template molecule and an ionic liquid as
      porogen, were injected into the silica monolith immobilized vinyl groups to form
      the molecularly imprinted films on the surface of the vinyl functionalized silica
      monolith. The monolithic materials were characterized by SEM, Fourier transform
      IR and solid-state reflection UV spectra. The resulted imprinted materials were
      evaluated under CEC and HPLC mode. The results indicated that there were enough
      recognition sites on the surface of the imprinted film-derivatized monolithic
      materials for selectively recognizing sulfamethazine from the sulfonamide
      mixture. Ionic liquids, which was utilized as the porogens, could improve the
      flow-through property and the imprinting effect of the molecularly imprinted film
      functionalized silica monolithic materials.

PMID- 20824657
TI  - Mitochondria and the culture of the Borg: understanding the integration of
      mitochondrial function within the reticulum, the cell, and the organism.
AB  - As endosymbionts, the mitochondria are unique among organelles. This review
      provides insights into mitochondrial behavior and introduces the idea of a
      unified collective, an interconnected reticulum reminiscent of the Borg, a
      fictional humanoid species from the Star Trek television series whereby decisions
      are made within their network (or "hive"), linked to signaling cascades that
      coordinate the cross-talk between mitochondrial and cellular processes ("subspace
      domain"). Similarly, mitochondrial dynamics are determined by two distinct
      processes, namely the local regulation of fission/fusion and the global control
      of their behavior through cellular signaling pathways. Indeed, decisions within
      the hive provide each mitochondrial unit with autonomous control of their own
      degradation, whereby mitochondrial fusion is inactivated and they become
      substrates for autophagy. Decisions within the subspace domain couple signaling
      pathways involved in the functional integration of mitochondria with complex
      cellular transitions, including developmental cues, mitosis, and apoptosis.

PMID- 20824659
TI  - Estimation of chromatographic lipophilicity of bile acids and their derivatives
      by reversed-phase thin layer chromatography.
AB  - The main goal of this study was to estimate the lipophilicity and investigate the
      molecular mechanism of retention of bile acids and their derivatives in order to
      find an objective manner of quantitative comparison of different chemically
      bonded stationary phases for high performance TLC in terms of their
      (dis)similarities. Highly significant correlations were obtained between
      different experimental indices of lipophilicity (R(M0), S and the scores
      corresponding to the first principal component) estimated on CN(F254s) and RP
      18(F254s) and some computed log P values that combine electronic and topological
      aspects. The most statistically significant quantitative structure-property
      relationship models, using descriptors from Dragon software, multiple linear
      regression and genetic algorithm, were also obtained in the case of CN(F254s) and
      RP-18(F254s) stationary phases. Cross-validation suggests a good reliability of
      the results. The contribution of 2D and 3D descriptors, which are related to
      atomic mass, together with reactivity parameters such as polarizability and
      electronegativity seem to control the chromatographic mechanism (lipophilicity)
      on all stationary phases.

PMID- 20824660
TI  - Triamine-bonded stationary phase for open tubular capillary
      electrochromatography.
AB  - A multi-functional separation column modified with 3-[2-(2
      aminoethylamino)ethylamino] propyl-trimethoxysilane was developed for open
      tubular capillary electrochromatography. This functional hydrophilic triamine
      bonded open tubular column could generate both anodic and cathodic EOF. When the
      pH of the running buffer was below 5.3 (30% 3-[2-(2-aminoethylamino)ethylamino]
      propyl-trimethoxysilane, v/v), the anodic EOF was exhibited, which greatly
      prevented the undesired adsorptions of basic proteins on the capillary inner
      wall. Favorable separation of four basic proteins (viz. trypsin, ribonuclease A,
      lysozyme and cytochrome c) was successfully achieved at pH 3.5 of 10  mmol/L
      phosphate buffer. The column efficiencies of proteins were in the range from
      87,000 to 110,000  plates/m, and the RSD values for migration time of four
      proteins were less than 1.2% (run-to-run, n=5). The ionic analytes were also
      separated efficiently in the co-electroosmotic mode. The average efficiencies
      ranged from 81,000 to 190,000  plates/m for seven aromatic acids and 186,000
      245,000  plates/m for four nucleoside monophosphates, respectively, and good
      capillary column repeatability was gained with RSD of the migration time not more
      than 3.0%. The triamine-bonded open tubular capillary column is favorable to be
      an alternative functional medium for the further analysis of basic proteins and
      anionic analytes.

PMID- 20824661
TI  - Rapid determination of caffeoylquinic acid derivatives in Cynara scolymus L. by
      ultra-fast liquid chromatography/tandem mass spectrometry based on a fused core
      C18 column.
AB  - An ultra-fast high-performance LC-ESI-MS/MS method was developed for the analysis
      and quantification of caffeoylquinic acid derivatives, including chlorogenic
      acid, 1,3-di-O-caffeoylquinic acid (cynarin) and 1,5-di-O-caffeoylquinic acid, in
      artichoke (Cynara scolymus L.) heads and leaves. The rapid separation (less than
      4  min) was achieved based on a Halo fused core C18-silica column (50  mm * 2.1 
      mm id, 2.7  MUm). The target compounds were detected and quantified by a triple
      quadrupole mass spectrometer in multiple-reaction monitoring mode. The
      calibration function is linear from 0.06 to 2800  ng/mL for chlorogenic acid, 0.3
      3000  ng/mL for cynarin and 0.24-4800  ng/mL for 1,5-di-O-caffeoylquinic acid,
      respectively. The average recoveries ranged from 92.1 to 113.2% with RSDs <=6.5%.
      Moreover, four batches of artichoke head and leaf extracts were analyzed using
      the established method. The results indicated that the Halo fused core column
      provided much faster separations and higher sample throughput without sacrificing
      column ruggedness and reliability, and triple-quadrupole MS provided
      extraordinarily lower LOQs for most of the target analytes. Comparing to
      conventional quantitative approaches, the established method was fast, sensitive
      and reliable for the determination of caffeoylquinic acid derivatives in
      artichoke.

PMID- 20824663
TI  - A review of the critical role of vitamin D in the functioning of the immune
      system and the clinical implications of vitamin D deficiency.
AB  - This review looks at the critical role of vitamin D in improving barrier
      function, production of antimicrobial peptides including cathelicidin and some
      defensins, and immune modulation. The function of vitamin D in the innate immune
      system and in the epithelial cells of the oral cavity, lung, gastrointestinal
      system, genito-urinary system, skin and surface of the eye is discussed. Clinical
      conditions are reviewed where vitamin D may play a role in the prevention of
      infections or where it may be used as primary or adjuvant treatment for viral,
      bacterial and fungal infections. Several conditions such as tuberculosis,
      psoriasis, eczema, Crohn's disease, chest infections, wound infections,
      influenza, urinary tract infections, eye infections and wound healing may benefit
      from adequate circulating 25(OH)D as substrate. Clinical diseases are presented
      in which optimization of 25(OH)D levels may benefit or cause harm according to
      present day knowledge. The safety of using larger doses of vitamin D in various
      clinical settings is discussed.

PMID- 20824662
TI  - Oral administration of docosahexaenoic acid attenuates colitis induced by dextran
      sulfate sodium in mice.
AB  - SCOPE: Dietary supplementation of n-3 PUFAs, containing docosahexaenoic acid
      (DHA), modulates the symptoms of colitis. Hence, we investigated the effects of
      oral administration of pure DHA and the therapeutic agent sulfasalazine (SAL) on
      chemically induced colitis in mice, and analyzed the expression levels of DHA
      responsive genes in colonic tissue using cDNA arrays. METHODS AND RESULTS:
      Colitis in BALB/c mice was induced by feeding 5% dextran sulfate sodium (DSS) in
      drinking water for 7 days. DHA (30 mg/kg/day, DHA) or SAL (100 mg/kg/day, SAL)
      was administered orally throughout the treatment along with DSS. The DHA-treated
      group showed significant reduction of the weight loss and colon shortening
      compared to the DSS-treated colitis group. In contrast, SAL treatment was
      effective in reducing colon shortening, stool consistency and bleeding scores.
      DHA and SAL treatments also significantly reduced the changes in inflammation of
      the colon, and reversed the increase in myeloperoxidase activity induced by DSS.
      Among DSS-responsive genes, those for inflammatory cytokines (IL-1beta, CD14
      antigen and tumor necrosis factor receptor superfamily, member 1b), membrane
      remodeling genes (matrix metalloproteinase-3, -10 and -13) and acute phase
      proteins (S100 calcium-binding protein A8), which were increased by DSS, were
      downregulated by DHA or SAL treatment. CONCLUSIONS: DHA was effective in
      alleviating DSS-induced colitis in mice, partly by modulating the expression
      levels of genes involved in colitis.

PMID- 20824664
TI  - The insulin sensitivity response is determined by the interaction between the
      G972R polymorphism of the insulin receptor substrate 1 gene and dietary fat.
AB  - SCOPE: Insulin resistance, a condition associated with type 2 diabetes mellitus,
      results from the interaction of environmental and genetic factors. The aim of
      this study was to explore the influence of the G972R polymorphism at the insulin
      receptor substrate 1 gene on insulin sensitivity in a healthy young population.
      Furthermore, we examined whether the presence of this single nucleotide
      polymorphism (SNP; GR or GG) interacts with dietary fat to modulate insulin
      sensitivity. METHODS AND RESULTS: Fifty-nine healthy volunteers consumed three
      diets during 4 wk each following a randomized crossover design: a saturated fatty
      acid diet, a low-fat and high carbohydrate (CHO) diet or a MUFA diet. For each
      diet, we investigated peripheral insulin sensitivity with the insulin suppression
      test. Steady-state plasma glucose and plasma-free fatty acids concentrations were
      significantly lower in GR subjects after the intake of a CHO diet, than did
      homozygous GG subjects (p<0.05). However, no differences were observed after
      consuming the two other diets. CONCLUSIONS: Insulin sensitivity increased in GR
      subjects for the G972R polymorphism at the insulin receptor substrate 1 gene
      locus, after intake of a CHO diet. Increased knowledge of how these and other
      genes influence insulin sensitivity should increase the understanding of
      personalized nutrition.

PMID- 20824665
TI  - A spider-web-like highly expandable sensor network for multifunctional materials.

PMID- 20824666
TI  - All-manganite tunnel junctions with interface-induced barrier magnetism.

PMID- 20824667
TI  - Benzobisthiazole-based semiconducting copolymers showing excellent environmental
      stability in high-humidity air.

PMID- 20824668
TI  - High-efficiency blue and white organic light-emitting devices incorporating a
      blue iridium carbene complex.

PMID- 20824669
TI  - Switchable transparency and wetting of elastomeric smart windows.

PMID- 20824670
TI  - Aqueous-phase synthesis of Pt/CeO2 hybrid nanostructures and their catalytic
      properties.

PMID- 20824671
TI  - Gender differences in self-reported late effects, quality of life and
      satisfaction with clinic in survivors of lymphoma.
AB  - OBJECTIVES: Gender differences in perceived vulnerability to late effects and
      views about follow-up among cancer survivors have received little attention. As
      lymphoma affects both genders similarly, we compared the consequences of cancer
      (late effects, perceived vulnerability and quality of life (health-related
      quality of life (HRQoL)), and satisfaction with clinic visits between genders.
      METHODS: A cohort of 115 younger adults (18-45 years, >5 years disease-free
      survival), who had been treated for lymphoma participated. Questionnaires (n =
      91) were completed before and after (n = 62) routine consultant-led appointments.
      Survivors (n = 24) without appointments were recruited by post. Questionnaires
      included HRQoL, late effects, perceived vulnerability, issues survivors wanted to
      discuss and reported discussing in clinic, time waiting in clinic and
      consultation satisfaction. RESULTS: There were no gender differences in number of
      self-reported late effects or perceived vulnerability. Men with more late effects
      reported worse psychological HRQoL (r = 0.50, p<0.001). While men wanted to
      discuss more topics than they did, women were able to discuss the topics they
      wanted (ANOVA, p = 0.01). Multiple regression analyses showed a shorter wait in
      clinic (r = -0.46, p = 0.009) and discussing more topics (r = 0.34, p = 0.06)
      explained 30.6% of the variance in consultation satisfaction for men.
      CONCLUSIONS: Issues surrounding follow-up provision are increasingly important
      given the length of survival in young adults following treatment for lymphoma.
      Men may experience poor psychological well-being due to distress about unanswered
      concerns. Consideration of their concerns should be prioritised, given that
      satisfaction and ultimately continued attendance at clinic and HRQoL may be
      dependent on the extent to which follow-up meets survivors' expectations.

PMID- 20824672
TI  - Primary rat hepatocyte culture on 3D nanofibrous polymer scaffolds for toxicology
      and pharmaceutical research.
AB  - Primary rat hepatocytes are a widely used experimental model to estimate drug
      metabolism and toxicity. In currently used two-dimensional (2D) cell culture
      systems, typical problems like morphological changes and the loss of liver cell
      specific functions occur. We hypothesize that the use of polymer scaffolds could
      overcome these problems and support the establishment of three-dimensional (3D)
      culture systems in pharmaceutical research. Isolated primary rat hepatocytes were
      cultured on collagen-coated nanofibrous scaffolds for 7 days. Cell loading
      efficiency was quantified via DNA content measurement. Cell viability and
      presence of liver-cell-specific functions (albumin secretion, glycogen storage
      capacity) were evaluated. The activity of liver-specific factors was analyzed by
      immunofluorescent staining. RNA was isolated to establish quantitative real-time
      PCR. Our results indicate that primary rat hepatocytes cultured on nanofibrous
      scaffolds revealed high viability and well-preserved glycogen storage. Albumin
      secretion was existent during the entire culture period. Hepatocytes remain HNF-4
      positive, indicating highly preserved cell differentiation. Aggregated
      hepatocytes re-established positive signaling for Connexin 32, a marker for
      differentiated hepatocyte interaction. ZO-1-positive hepatocytes were detected
      indicating formation of tight junctions. Expression of cytochrome isoenzymes was
      inducible. Altogether the data suggest that nanofibrous scaffolds provide a good
      in vitro microenvironment for neo tissue regeneration of primary rat hepatocytes.

PMID- 20824673
TI  - High-throughput screening of a small molecule library for promoters and
      inhibitors of mesenchymal stem cell osteogenic differentiation.
AB  - The use of high-throughput screening (HTS) techniques has long been employed by
      the pharmaceutical industry to increase discovery rates for new drugs that could
      be useful for disease treatment, yet this technology has only been minimally
      applied in other applications such as in tissue regeneration. In this work, an
      assay for the osteogenic differentiation of human mesenchymal stem cells (hMSCs)
      was developed and used to screen a library of small molecules for their potential
      as either promoters or inhibitors of osteogenesis, based on levels of alkaline
      phosphatase activity and cellular viability. From a library of 1,040 molecules,
      36 promoters, and 20 inhibitors were identified as hits based on statistical
      criteria. Osteopromoters from this library were further investigated using
      standard culture techniques and a wider range of outcomes to verify that these
      compounds drive cellular differentiation. Several hits led to some improvement in
      the expression of alkaline phosphatase, osteogenic gene expression, and matrix
      mineralization by hMSCs when compared to the standard dexamethasone supplemented
      media and one molecule was investigated in combination with a recently identified
      biodegradable and osteoconductive polymer. This work illustrates the ability of
      HTS to more rapidly identify potential molecules to control stem cell
      differentiation.

PMID- 20824674
TI  - Reaction-diffusion constraints in living tissue: effectiveness factors in
      skeletal muscle design.
AB  - A mathematical model was developed to analyze the effects of intracellular
      diffusion of O(2) and high-energy phosphate metabolites on aerobic energy
      metabolism in skeletal muscle. We tested the hypotheses that in a range of muscle
      fibers from different species (1) aerobic metabolism was not diffusion limited
      and (2) that fibers had a combination of rate and fiber size that placed them at
      the brink of substantial diffusion limitation. A simplified chemical reaction
      rate law for mitochondrial oxidative phosphorylation was developed utilizing a
      published detailed model of isolated mitochondrial function. This rate law was
      then used as a boundary condition in a reaction-diffusion model that was further
      simplified using the volume averaging method and solved to determine the rates of
      oxidative phosphorylation as functions of the volume fraction of mitochondria,
      the size of the muscle cell, and the amount of oxygen delivered by the
      capillaries. The effectiveness factor, which is the ratio of reaction rate in the
      system with finite rates of diffusion to those in the absence of any diffusion
      limitations, defined the regions where intracellular diffusion of metabolites and
      O(2) may limit aerobic metabolism in both very small, highly oxidative fibers as
      well as in larger fibers with lower aerobic capacity. Comparison of model
      analysis with experimental data revealed that none of the fibers was strongly
      limited by diffusion, as expected. However, while some fibers were near
      substantial diffusion limitation, most were well within the domain of reaction
      control of aerobic metabolic rate. This may constitute a safety factor in muscle
      that provides a level of protection from diffusion constraints under conditions
      such as hypoxia.

PMID- 20824675
TI  - Enhanced butyric acid tolerance and bioproduction by Clostridium tyrobutyricum
      immobilized in a fibrous bed bioreactor.
AB  - Repeated fed-batch fermentation of glucose by Clostridium tyrobutyricum
      immobilized in a fibrous bed bioreactor (FBB) was successfully employed to
      produce butyric acid at a high final concentration as well as to adapt a butyric
      acid-tolerant strain. At the end of the eighth fed-batch fermentation, the
      butyric acid concentration reached 86.9 +/- 2.17 g/L, which to our knowledge is
      the highest butyric acid concentration ever produced in the traditional
      fermentation process. To understand the mechanism and factors contributing to the
      improved butyric acid production and enhanced acid tolerance, adapted strains
      were harvested from the FBB and characterized for their physiological properties,
      including specific growth rate, acid-forming enzymes, intracellular pH, membrane
      bound ATPase and cell morphology. Compared with the original culture used to seed
      the bioreactor, the adapted culture showed significantly reduced inhibition
      effects of butyric acid on specific growth rate, cellular activities of butyric
      acid-forming enzyme phosphotransbutyrylase (PTB) and ATPase, together with
      elevated intracellular pH, and elongated rod morphology.

PMID- 20824676
TI  - Necessary and sufficient conditions for the asymmetric synthesis of chiral amines
      using omega-aminotransferases.
AB  - The half reactions of omega-aminotransferase (omega-AT) from Vibrio fluvialis
      JS17 (omega-ATVf) were carried out using purified pyridoxal 5'-phosphate-enzyme
      (PLP-Enz) and pyridoxamine 5'-phosphate-enzyme (PMP-Enz) complexes to investigate
      the relative activities of substrates. In the reaction generating PMP-Enz from
      PLP-Enz using L-alanine as an amine donor, L-alanine showed about 70% of the
      initial reaction rate of (S)-alpha-methylbenzylamine ((S)-alpha-MBA). However, in
      the subsequent half reaction recycling PLP-Enz from PMP-Enz using acetophenone as
      an amine acceptor, acetophenone showed nearly negligible reactivity compared to
      pyruvate. These results indicate that the main bottleneck in the asymmetric
      synthesis of (S)-alpha-MBA lies not in the amination of PLP by alanine, but in
      the amination of acetophenone by PMP-Enz, where conformational restraints of the
      enzyme structure is likely to be the main reason for limiting the amine group
      transfer from PMP-Enz to acetophenone. Based upon those half reaction experiments
      using the two amino acceptors of different activity, it appears that the relative
      activities of the two amine donors and the two acceptors involved in the omega-AT
      reactions can roughly determine the asymmetric synthesis yield of the target
      chiral amine compound. Predicted conversion yields of several target chiral
      amines were calculated and compared with the experimental conversion yields.
      Approximately, a positive linear correlation (Pearson's correlation coefficient =
      0.92) was observed between the calculated values and the experimental conversion
      yields. To overcome the low (S)-alpha-MBA productivity of omega-ATVf caused by
      the possible disadvantageous structural constraints for acetophenone, new omega
      ATs showing higher affinity to benzene ring of acetophenone than omega-ATVf were
      computationally screened using comparative modeling and protein-ligand docking.
      omega-ATs from Streptomyces avermitilis MA-4680 (SAV2612) and Agrobacterium
      tumefaciens str. C58 (Atu4761) were selected, and the two screened omega-ATs
      showed higher asymmetric synthesis reaction rate of (S)-alpha-MBA and lower (S)
      alpha-MBA degradation reaction rate than omega-ATVf. To verify the higher
      conversion yield of the variants of omega-ATs, the reaction with 50 mM
      acetophenone and 50 mM alanine was performed with coupling of lactate
      dehydrogenase and two-phase reaction system. SAV2612 and Atu4761 showed 70% and
      59% enhanced yield in the synthesis of (S)-alpha-MBA compared to that of omega
      ATVf, respectively.

PMID- 20824677
TI  - Antimicrobial testing for surface-immobilized agents with a surface-separated
      live-dead staining method.
AB  - Modification of a traditional live-dead staining technique based on fluorescence
      microscopy has yielded an improved method capable of differentiating surface
      immobilized antimicrobial agents from those agents acting via solution diffusion
      processes. By utilizing an inoculation chamber comprised of 50 um polystyrene
      spheres as spacers between test substrate and coverslip control surfaces, three
      distinct bacterial cell populations can be probed by fluorescence microscopy for
      antimicrobial activity: (1) cells adhered to the coverslip, (2) cells adhered to
      the substrate, and (3) mobile cells in solution. Truly immobilized antimicrobial
      agents were found efficacious only at the substrate surface, while elutable
      agents were effective against all three populations. Glass surfaces derivatized
      with either quaternized poly dimethylaminoethylmethacrylate (pDMAEMA) or 3
      (trimethoxysilyl) propyldimethyloctadecyl ammonium chloride (Si-QAC) were
      compared with bare glass control surfaces after contact and 4 h incubation with
      Staphylococcus aureus. pDMAEMA surfaces were both antimicrobial and immobilized,
      whereas the Si-QAC surfaces were only observed to be antimicrobial via active
      diffusion. In contrast to conventional thinking, Si-QAC surfaces showed no kill
      after removing all Si-QAC elutables via rinsing procedures. The semi-quantitative
      surface-separated live-dead staining (SSLDS) technique provides mechanistic
      insight and represents a significant improvement relative to current
      microbiological test methods for evaluating immobilized, antimicrobial agents.

PMID- 20824678
TI  - Efficacy and safety of saxagliptin in combination with metformin compared with
      sitagliptin in combination with metformin in adult patients with type 2 diabetes
      mellitus.
AB  - BACKGROUND: Dipeptidyl peptidase-4 inhibitors improve glycaemic control in
      patients with type 2 diabetes mellitus when used as monotherapy or in combination
      with other anti-diabetic drugs (metformin, sulphonylurea, or thiazolidinedione).
      This 18-week, phase 3b, multicentre, double-blind, noninferiority trial compared
      the efficacy and safety of two dipeptidyl peptidase-4 inhibitors, saxagliptin and
      sitagliptin, in patients whose glycaemia was inadequately controlled with
      metformin. METHODS: Adult type 2 diabetes mellitus patients (N = 801) with
      glycated haemoglobin (HbA(1c)) 6.5-10% on stable metformin doses (1500-3000
      mg/day) were randomized 1 : 1 to add-on 5 mg saxagliptin or 100 mg sitagliptin
      once daily for 18 weeks. The primary efficacy analysis was a comparison of the
      change from baseline HbA(1c) at week 18 in per-protocol patients. Noninferiority
      was concluded if the upper limit of the two-sided 95% confidence interval of the
      HbA(1c) difference between treatments was < 0.3%. RESULTS: The adjusted mean
      changes in HbA(1c) following the addition of saxagliptin or sitagliptin to stable
      metformin therapy were - 0.52 and - 0.62%, respectively. The between-group
      difference was 0.09% (95% confidence interval, - 0.01 to 0.20%), demonstrating
      noninferiority. Both treatments were generally well tolerated; incidence and
      types of adverse events were comparable between groups. Hypoglycaemic events,
      mostly mild, were reported in approximately 3% of patients in each treatment
      group. Body weight declined by a mean of 0.4 kg in both groups. CONCLUSIONS:
      Saxagliptin added to metformin therapy was effective in improving glycaemic
      control in patients with type 2 diabetes mellitus inadequately controlled by
      metformin alone; saxagliptin plus metformin was noninferior to sitagliptin plus
      metformin, and was generally well tolerated.

PMID- 20824679
TI  - A novel herbicide-inducible male sterility system.
AB  - BACKGROUND: Heterosis is a phenomenon that first-generation offspring perform
      better than their parents. Conventional breeding methods have their shortcomings.
      It would be optimal to construct inducible male sterile plants. RESULTS: We
      developed a novel system for creating male sterile transgenic plants by
      downregulating the specific expression of the glyphosate tolerance CP4 EPSPS gene
      in male reproductive tissues. Transcriptional repression was achieved by
      manipulating DNA binding proteins with their specific corresponding sites. We
      transferred the CP4 EPSPS gene driven by a modified CaMV 35S promoter with three
      tetracycline operator copies in the vicinity of the TATA box and tetracycline
      repressor gene under the control of an anther-specific promoter Osg6B to
      Arabidopsis thaliana. As a result, we successfully obtained controllable
      transgenic plants: the whole plant could tolerate exposure of glyphosate but the
      male tissue was sensitive. CONCLUSION: The novel inducible male sterility system
      is applied and easy to handle, so it might be applicable to a wide range of crop
      plants.

PMID- 20824680
TI  - Salvianolic acid B inhibits low-density lipoprotein oxidation and neointimal
      hyperplasia in endothelium-denuded hypercholesterolaemic rabbits.
AB  - BACKGROUND: Atherosclerosis and restenosis are inflammatory responses involving
      free radicals and lipid peroxidation and may be prevented/cured by antioxidant
      mediated lipid peroxidation inhibition. Salvianolic acid (Sal B), a water-soluble
      antioxidant obtained from a Chinese medicinal herb, is believed to have multiple
      preventive and therapeutic effects against human vascular diseases. In this study
      the in vitro and in vivo inhibitory effects of Sal B on oxidative stress were
      determined. RESULTS: In human aortic endothelial cells (HAECs), Sal B reduced
      oxidative stress, inhibited low-density lipoprotein (LDL) oxidation and reduced
      oxidised LDL-induced cytotoxicity. Sal B inhibited Cu(2+) -induced LDL oxidation
      in vitro (with a potency 16.3 times that of probucol) and attenuated HAEC
      mediated LDL oxidation as well as reactive oxygen species (ROS) production. In
      cholesterol-fed New Zealand White rabbits (with probucol as positive control),
      Sal B intake reduced Cu(2+) -induced LDL oxidation, lipid deposition in the
      thoracic aorta, intimal thickness of the aortic arch and thoracic aorta and
      neointimal formation in the abdominal aorta. CONCLUSION: The data obtained in
      this study suggest that Sal B protects HAECs from oxidative injury-mediated cell
      death via inhibition of ROS production. The antioxidant activity of Sal B may
      help explain its efficacy in the treatment of vascular diseases.

PMID- 20824681
TI  - Effect of thiamethoxam on cockroach locomotor activity is associated with its
      metabolite clothianidin.
AB  - BACKGROUND: In the present study, the effect of thiamethoxam and clothianidin on
      the locomotor activity of American cockroach, Periplaneta americana (L.), was
      evaluated. Because it has been proposed that thiamethoxam is metabolised to
      clothianidin, high-performance liquid chromatography coupled with mass
      spectrometry was used to evaluate the amount of clothianidin on thiamethoxam
      treated cockroaches. RESULTS: One hour after neonicotinoid treatment, the time
      spent in the open-field-like apparatus significantly increased, suggesting a
      decrease in locomotor activity. The percentage of cockroaches displaying
      locomotor activity was significantly reduced 1 h after haemolymph application of
      1 nmol g(-1) neonicotinoid, while no significant effect was found after topical
      and oral administration. However, at 24 and 48 h, all neonicotinoids were able to
      reduce locomotor activity, depending on their concentrations and the way they
      were applied. Interestingly, it was found that thiamethoxam was converted to
      clothianidin 1 h after application, but the amount of clothianidin did not rise
      proportionately to thiamethoxam, especially after oral administration.
      CONCLUSION: The data suggest that the effect of thiamethoxam on cockroach
      locomotor activity is due in part to clothianidin action because (1) thiamethoxam
      levels remained persistent 48 h after application and (2) the amount of
      clothianidin in cockroach tissues was consistent with the toxicity of
      thiamethoxam.

PMID- 20824682
TI  - Nutrient acquisition and limitation for the photoautotrophic growth of
      Synechocystis sp. PCC6803 as a renewable biomass source.
AB  - Photoautotrophic microorganisms (cyanobacteria and algae) offer high promise as a
      source of biomass for renewable energy due to their rapid growth rates and high
      biomass yields. To provide a framework for evaluating the feasibility of growing
      phototrophic microorganisms with high biomass production rates, we operated a
      bench-scale photobioreactor using Synechocystis sp. PCC6803 and with light
      conditions imitating actual day-night light irradiance (LI). During the time of
      peak LI, PCC6803's specific growth rate (1.7 day-1) and the nitrate uptake rate
      (0.46 g N/g DW day) were high compared to past reports. Analysis employing the
      stoichiometry of photosynthesis of PCC6803 and ionic speciation showed that
      bicarbonate and phosphate were driven to very low concentrations for the high-LI
      conditions. In particular, the systematic evaluation of rate-limiting factors
      identified when the CO2-C(i) supply rate needed to be increased to mitigate HCO3-
      depletion and a large pH increase. It also showed that the traditional BG-11
      medium needs to be augmented with phosphate to avoid severe P depletion. This
      work exploits quantitative understanding the stoichiometry and kinetics of
      cyanobacteria for the high-rate production of a renewable biomass.

PMID- 20824683
TI  - Environmental effect on yield, composition and technological seed traits of some
      Italian ecotypes of grass pea (Lathyrus sativus L.).
AB  - BACKGROUND: Grass pea seeds are a good source of vegetable proteins, but the
      presence of toxic and antinutritional compounds represents a barrier to their
      large-scale use as food or animal feed. How much growing location and/or seasonal
      climate might affect the storage of these factors has been little investigated.
      RESULTS: Fourteen Italian ecotypes of grass pea were cultivated in two locations
      in southern Italy characterised by different climatic conditions. The seven
      ecotypes with the best yields and/or seed quality were investigated for a further
      two growing seasons. From a statistical point of view the physicochemical and
      nutritional traits among ecotypes were not the same from one year to the next.
      Moreover, a significant positive correlation was found between beta-oxalyl
      diamino-propionic acid and trypsin inhibitor contents. The lowest levels of both
      these compounds were associated with the highest amount of rainfall during the
      plant vegetative cycle. CONCLUSION: Principal component analysis of the data
      showed that the overall seed composition was affected by the growing location.
      Consequently, each grass pea genotype should also be carefully investigated in
      relation to different environments before being considered for release as safe
      for widespread human or animal consumption.

PMID- 20824684
TI  - Characterisation and functional properties of watermelon (Citrullus lanatus) seed
      proteins.
AB  - BACKGROUND: People in developing countries depend largely on non-conventional
      protein sources to augment the availability of proteins in their diets.
      Watermelon seed meal is reported to contain an adequate amount of nutritional
      proteins that could be extracted for use as nutritional ingredients in food
      products. RESULTS: Osborne classification showed that globulin was the major
      protein (>=500 g kg (-1)) present in watermelon seed meal, followed by albumin
      and glutelin. Sodium dodecyl sulfate polyacrylamide gel electrophoresis indicated
      that the polypeptides had low molecular weights ranging from 35 to 47 kDa.
      Isoelectric focusing revealed that the isoelectric point of most proteins was in
      the acidic range 4-6. These proteins are rich in aspartic acid, glutamic acid and
      serine. An increase in pH (5-9) significantly (P < 0.05) decreased the
      denaturation enthalpy of these proteins. Among functional properties, albumin
      exhibited a much higher dispersibility index (810.3-869.6 g kg(-1)) than globulin
      (227.8-245.4 g kg(-1)), glutelin (182.1-187.7 g kg(-1)) and prolamin (162.3-177.7
      g kg(-1)). Digestibility was in the ranges 760.6-910.0 and 765.5-888.5 g kg(-1)
      for Mateera and Sugar Baby watermelon protein fractions respectively, while
      surface hydrophobicity ranged from 126.4 to 173.2 and from 125.8 to 169.3
      respectively. The foaming and emulsifying properties of albumin were better than
      those of the other proteins studied. CONCLUSION: The good nutritional and
      functional properties of watermelon seed meal proteins suggest their potential
      use in food formulations.

PMID- 20824685
TI  - Biotype and insecticide resistance status of the whitefly Bemisia tabaci from
      China.
AB  - BACKGROUND: Resistance to numerous insecticide classes in Bemisia tabaci
      Gennadius has impaired field control efficacy in south-eastern China. The biotype
      and resistance status of B. tabaci collected from these areas was investigated.
      RESULTS: Two different biotypes of B. tabaci (B-biotype and Q-biotype) were
      detected in south-eastern China, and the samples collected from geographical
      regions showed a prevalence of the Q-biotype and the coexistence of B- and Q
      biotypes in some regions. Moderate to high levels of resistance to two
      neonicotinoids were established in both biotypes (28-1900-fold to imidacloprid,
      29-1200-fold to thiamethoxam). Medium to high levels of resistance to alpha
      cypermethrin (22-610-fold) were also detected in both biotypes. Four out of 12
      populations had low to medium levels of resistance to fipronil (10-25-fold). Four
      out of 12 populations showed low levels of resistance to spinosad (5.7-6.4-fold).
      All populations tested were susceptible to abamectin. CONCLUSION: The Q-biotype
      B. tabaci is supplanting the B-biotype which used to be ubiquitous in China.
      Field populations of both B- and Q-biotypes of B. tabaci have developed high
      levels of resistance to imidacloprid and thiamethoxam. Abamectin is the most
      effective insecticide against adult B. tabaci from all populations.

PMID- 20824687
TI  - Exploratory sensory profiling of three culinary preparations of potatoes (Solanum
      tuberosum L.).
AB  - BACKGROUND: A consumer-oriented description of potato quality with regard to
      culinary preparation could increase potato consumption. The aim of this study was
      to investigate the sensory attributes in 11 potato varieties grown at two
      locations and used for three culinary preparations. RESULTS: Sensory evaluation
      of the potatoes served either as boiled, oven-fried or mashed were performed
      using 15-19 descriptors for appearance, flavour and texture attributes. A
      principal component analysis revealed that 45% of the variation in the sensory
      data was related to variety differences, which was ascribed to variation in
      appearance, dry matter content and texture. Growing location also significantly
      affected appearance and texture. CONCLUSION: The sensory panel judged the sensory
      attributes 'yellowness', 'hardness', 'adhesiveness' and 'moistness' to be
      important quality descriptors in all three culinary preparations. Internal
      references showed the high reproducibility of the sensory evaluations. The
      potatoes grown in a sandy location had higher content of dry matter compared to
      those grown in a clay location, affecting the quality. This study showed that it
      was possible to do reliable and reproducible sensory profiles in a potato
      material with a large span in quality. Sensory information based on few
      attributes can be used to describe culinary quality of potato varieties.

PMID- 20824686
TI  - Patient falls: Association with hospital Magnet status and nursing unit staffing.
AB  - The relationships between hospital Magnet(r) status, nursing unit staffing, and
      patient falls were examined in a cross-sectional study using 2004 National
      Database of Nursing Quality Indicators (NDNQI(r)) data from 5,388 units in 108
      Magnet and 528 non-Magnet hospitals. In multivariate models, the fall rate was 5%
      lower in Magnet than non-Magnet hospitals. An additional registered nurse (RN)
      hour per patient day was associated with a 3% lower fall rate in ICUs. An
      additional licensed practical nurse (LPN) or nursing assistant (NA) hour was
      associated with a 2-4% higher fall rate in non-ICUs. Patient safety may be
      improved by creating environments consistent with Magnet hospital standards.

PMID- 20824688
TI  - Re-structuring protein crystals porosity for biotemplating by chemical
      modification of lysine residues.
AB  - Protein crystals are routinely prepared for the elucidation of protein structure
      by X-ray crystallography. These crystals present an highly accurate periodical
      array of protein molecules with accompanying highly ordered porosity made of
      interconnected voids. The permeability of the porous protein crystals to a wide
      range of solutes has recently triggered attempts to explore their potential
      application as biotemplates by a controlled "filling" process for the fabrication
      of novel, nano-structured composite materials. Gaining control of the porosity of
      a given protein crystal may lead to the preparation of a series of "biotemplates"
      enabling different 'filler'/protein content ratios, resulting in different
      nanostructured composites. One way to gain such control is to produce a series of
      polymorphic forms of a given "parent-protein" crystal. As protein packing
      throughout crystallization is primarily dominated by the chemical composition of
      the surface of protein molecules and its impact on protein-protein interactions,
      modification of residues exposed on the surface will affect protein packing,
      leading to modified porosity. Here we propose to provide influence on the
      porosity of protein crystals for biotemplating by pre-crystallization chemical
      modification of lysine residues exposed on protein's surface. The feasibility of
      this approach was demonstrated by the serial application of chemical "modifiers"
      leading to protein derivatives exhibiting altered porosity by affecting protein
      "packing" throughout protein crystallization. Screening of a series of modifying
      agents for lysine modification of hen egg white lysozyme revealed that pre
      crystallization modification preserving their positive charge did not affect
      crystal porosity, while modification resulting in their conversion to negatively
      charged groups induced dramatic change in protein crystal's packing and porosity.
      Furthermore, we demonstrate that chemical modification of lysine residues
      affecting modified protein packing may be simultaneously performed with the
      crystallization process: aldehydes generating Schiff base formation with
      protein's lysine residues readily affected modified protein packing, resulting in
      altered porosity. Our results demonstrate the feasibility of the use of site
      directed chemical modifications for the generation of a series of protein crystal
      exhibiting different porosities for biotemplating, all derived from one "parent"
      protein.

PMID- 20824689
TI  - Understanding tissue specific compositions of bioenergy feedstocks through
      hyperspectral Raman imaging.
AB  - Hyperspectral Raman imaging was used to study the tissue/cell type specific
      distribution of lignin and cellulose polymers within the plant cell walls.
      Distinct differences in cell wall compositions were identified between two
      potential bioenergy feedstocks: corn stover and Eucalyptus globulus.
      Characteristic bands of 627, 1,175, 1,206, and 1,428 cm-1 were only observed for
      corn stover and 1,381 cm-1 was only present in E. globulus. One-dimensional and
      two-dimensional chemical maps of lignin and cellulose were generated for the stem
      of corn stover, ranging from the epidermis to the pith area and revealed that
      lignin and cellulose abundance varies significantly among different cell types in
      the following order: sclerenchyma cells and tracheids (~5 times) > epidermal
      cells (~3 times) > bundle sheath cells > parenchyma cells. The Raman mapping
      methods developed on corn stover were also validated on E. globulus and clearly
      highlighted their difference in lignin composition.

PMID- 20824690
TI  - Optimised expression and spectral analysis of the target enzyme CYP51 from
      Penicillium digitatum with possible new DMI fungicides.
AB  - BACKGROUND: Sterol 14alpha-demethylase (CYP51), a key target of azole (DMI)
      fungicides, can be expressed in both prokaryotes and eukaryotes. Green mould of
      citrus, caused by Penicillium digitatum (Pers.) Sacc., is a serious post-harvest
      disease. To develop specific and more effective fungicides against this disease,
      the characteristics of the interaction between sterol 14alpha-demethylase from P.
      digitatum (PdCYP51) and possible new fungicides were analysed. The cyp51 gene of
      P. digitatum was cloned and expressed under different conditions in Escherichia
      coli (Mig.) Cast. & Chalm., and the binding spectra of PdCYP51 were explored by
      the addition of two commercial azoles and four new nitrogen compounds. RESULTS:
      The yield of soluble protein (PdCYP51) was largest when expressed in Rosetta
      (DE3) induced by 0.5 mM IPTG for 8 h at 30  degrees C. Compound B (7-methoxy-2H
      benzo[b][1,4]thiazine-3-amine) showed the strongest binding activity of the four
      new nitrogen compounds, with a K(d) value of 0.268 uM. The K(d) values of the six
      compounds were significantly correlated with their EC(50) values. CONCLUSION: The
      spectral analysis and bioassay results could be used to screen the new chemical
      entities effectively. Compound B, selected by virtual screening from a commercial
      chemical library, is a candidate for a new DMI fungicide. These results provide a
      theoretical basis and new ideas for efficient design and development of new
      antifungal agents.

PMID- 20824691
TI  - Novel 'nano in nano' composites for sustained drug delivery: biodegradable
      nanoparticles encapsulated into nanofiber non-wovens.
AB  - Novel 'nano in nano' composites consisting of biodegradable polymer nanoparticles
      incorporated into polymer nanofibers may efficiently modulate drug delivery. This
      is shown here using a combination of model compound-loaded biodegradable
      nanoparticles encapsulated in electrospun fibers. The dye coumarin 6 is used as
      model compound for a drug in order to simulate drug release from loaded
      poly(lactide-co-glycolide) nanoparticles. Dye release from the nanoparticles
      occurs immediately in aqueous solution. Dye-loaded nanoparticles which are
      encapsulated by electrospun polymer nanofibers display a significantly retarded
      release.

PMID- 20824692
TI  - Functionalization of silk fibroin with NeutrAvidin and biotin.
AB  - New methods are needed to modify silk biomaterials with bioactive molecules for
      tissue engineering and drug delivery. In the present study, silk fibroin in
      solution or in microsphere format was coupled with NeutrAvidin via carbodiimide
      chemistry. Silk fibroin retained its self-assembly features after reaction. It
      was found that more than four NeutrAvidin molecules bound to one silk molecule.
      Non-specific binding of biotin or NeutrAvidin to silk microspheres could be
      reduced by pre-treatment of the microspheres with BSA or post-treatment with
      detergent. The NeutrAvidin-coupled silk microspheres were coupled with
      biotinylated anti-CD3 antibody and the functionalized microspheres were able to
      specifically bind to the CD3 positive T-lymphocytic cell line Jurkat.

PMID- 20824693
TI  - Conjugation of methacrylamide groups to a model protein via a reducible linker
      for immobilization and subsequent triggered release from hydrogels.
AB  - An efficient strategy is reported to introduce methacrylamide groups on the
      lysine residues of a model protein (lysozyme) for immobilization and triggered
      release from a hydrogel network. A novel spacer unit was designed, containing a
      disulfide bond, such that the release of the protein can be triggered by
      reduction. The modified proteins were characterized by MALDI-TOF MS, titration of
      free NH(2) residues and spectral analysis. The modification reaction is well
      controlled, and the number of introduced functions can be tailored by changing
      the reaction conditions. Gel electrophoresis experiments showed that the
      methacrylamide modified protein can be immobilized in a polyacrylamide hydrogel
      and subsequently released by reduction of the spacer by which the protein was
      grafted to the polymeric network.

PMID- 20824694
TI  - Crosstalk of osteoblast and osteoclast precursors on mineralized collagen-
      towards an in vitro model for bone remodeling.
AB  - Bone remodeling and, therefore, integration of implant materials require the
      coordinated regulation of osteoblast and osteoclast activity. This is why the in
      vitro evaluation of biomaterials for bone regeneration should involve not only
      the analysis of osteoblast differentiation but also the formation and
      differentiation of osteoclasts. In the present study, we applied a material made
      of mineralized collagen I that mimics extracellular bone matrix to establish a
      culture system, which allows the cocultivation of human monocytes and human
      mesenchymal stem cells (hMSCs), which were differentiated into osteoclast-like
      cells and osteoblasts, respectively. Both cell types were cultivated on membrane
      like structures from mineralized collagen. Transwell inserts were used to
      spatially separate the cell types but allowed exchange of soluble factors. The
      osteoclastogenesis and osteogenic differentiation were evaluated by analysis of
      gene expression, determination of alkaline phosphatase (ALP), and tartrate
      resistant acidic phosphatase (TRAP) activity. Furthermore, cell morphology was
      studied using scanning electron and transmission electron microscopy.
      Osteogenically induced hMSC showed an increased specific ALP activity as well as
      increased gene expression of gene coding for alkaline phosphatase (ALPL), when
      cocultivated with differentiating osteoclasts. Adipogenic differentiation of
      hMSCs was suppressed by the presence of osteoclasts as indicated by a major
      decrease in adipocyte cell number and a decrease in gene expression of adipogenic
      markers. The formation of multinucleated osteoclasts seems to be decreased in the
      presence of osteogenically induced hMSC as indicated by electron microscopic
      evaluation and determination of TRAP activity. However, gene expression of
      osteoclast markers was not decreased in coculture with osteogenically induced
      hMSC.

PMID- 20824695
TI  - The novel histone deacetylase inhibitor, AR-42, inhibits gp130/Stat3 pathway and
      induces apoptosis and cell cycle arrest in multiple myeloma cells.
AB  - Multiple myeloma (MM) remains incurable with current therapy, indicating the need
      for continued development of novel therapeutic agents. We evaluated the activity
      of a novel phenylbutyrate-derived histone deacetylase inhibitor, AR-42, in
      primary human myeloma cells and cell lines. AR-42 was cytotoxic to MM cells at a
      mean LC(50) of 0.18 +/- 0.06 MUmol/l at 48 hr and induced apoptosis with cleavage
      of caspases 8, 9 and 3, with cell death largely prevented by caspase inhibition.
      AR-42 downregulated the expression of gp130 and inhibited activation of STAT3,
      with minimal effects on the PI3K/Akt and MAPK pathways, indicating a predominant
      effect on the gp130/STAT-3 pathway. AR-42 also inhibited interleukin (IL)-6
      induced STAT3 activation, which could not be overcome by exogenous IL-6. AR-42
      also downregulated the expression of STAT3-regulated targets, including Bcl-xL
      and cyclin D1. Overexpression of Bcl-xL by a lentivirus construct partly
      protected against cell death induced by AR-42. The cyclin dependent kinase
      inhibitors, p16 and p21, were also significantly induced by AR-42, which together
      with a decrease in cyclin D1, resulted in G(1) and G(2) cell cycle arrest. In
      conclusion, AR-42 has potent cytotoxicity against MM cells mainly through
      gp130/STAT-3 pathway. The results provide rationale for clinical investigation of
      AR-42 in MM.

PMID- 20824696
TI  - Anti-breast cancer potential of SS5020, a novel benzopyran antiestrogen.
AB  - Treatment with tamoxifen (TAM) increases the risk of developing endometrial
      cancer in women. The carcinogenic effect is thought to involve initiation and/or
      promotion resulting from DNA damage induced by TAM as well as its estrogenic
      action. To minimize this serious side-effect while increasing the anti-breast
      cancer potential, a new benzopyran antiestrogen, 2E-3-{4-[(7-hydroxy-2-oxo-3
      phenyl-2H-chromen-4-yl)-methyl]-phenyl}-acrylic acid (SS5020), was synthesized.
      Unlike TAM, SS5020 exhibits no genotoxic activity to damage DNA. Furthermore,
      SS5020 does not present significant uterotrophic potential in rats; in contrast,
      the structurally related compounds, TAM, toremifene, raloxifene (RAL) and
      SP500263 all have uterotrophic activity. At the human equivalent molar dose of
      TAM (0.33 or 1.0 mg/kg), SS5020 had much stronger antitumor potential than those
      same antiestrogens against 7,12-dimethylbenz(a)anthracene-induced mammary
      carcinoma in rats. The growth of human MCF-7 breast cancer xenograft implanted
      into athymic nude mice was also effectively suppressed by SS5020. SS5020, lacking
      genotoxic and estrogenic actions, could be a safer and stronger antiestrogen
      alternative to TAM and RAL for breast cancer therapy and prevention.

PMID- 20824697
TI  - Restoring sensitivity to oxaliplatin by a novel approach in gemcitabine-resistant
      pancreatic cancer cells in vitro and in vivo.
AB  - Oxaliplatin (OxP) has been used in combination therapy with gemcitabine for the
      treatment of pancreatic cancer (PC), but the beneficial effect was marginal,
      which is believed to be due to de novo and acquired drug resistance of PC. Here,
      we report our in vitro and in vivo preclinical evidence in support of
      chemosensitization of drug-resistant cells by a nontoxic chemopreventive agent
      (genistein). Genistein pretreatment together with low concentration of OxP showed
      significant reduction in cell viability and colony formation concomitant with
      increased apoptosis (p < 0.01), which was highly synergistic. Drug resistance of
      PC is allegedly linked with both constitutive and OxP-induced activation of NF
      kappaB, and we found that inactivation of (nuclear factor kappa B) NF-kappaB by
      genistein before treatment of cells with OxP was required for cell killing, which
      was consistent with the downregulation of NF-kappaB and its downstream
      antiapoptotic genes (Bcl-2, XIAPs and survivin). Most importantly, our in vivo
      experiments using orthotopic mouse model showed significant reduction in tumor
      size (p < 0.01) and reduction of locoregional lymph node metastasis by
      combination treatment. These results were also consistent with inactivation of NF
      kappaB and the downregulation of NF-kappaB downstream genes, decreased
      proliferation marker (Ki-67) and increased apoptosis (TUNEL) in tumor remnants,
      all of which was consistent with in vitro findings. From these results, we
      conclude that genistein sensitizes drug-resistant PC to OxP, which is
      mechanistically linked with inactivation of NF-kappaB signaling, resulting in
      greater antitumor effects, and thus our data suggest that this approach could be
      useful in improving the treatment outcome for patients diagnosed with PC.

PMID- 20824698
TI  - Synergistic activation by p38MAPK and glucocorticoid signaling mediates induction
      of M2-like tumor-associated macrophages expressing the novel CD20 homolog MS4A8A.
AB  - Tumor-associated macrophages (TAMs) represent alternatively activated (M2)
      macrophages that support tumor growth. Previously, we have described a special
      LYVE-1(+) M2 TAM subset in vitro and in vivo; gene profiling of this TAM subset
      identified MS4A8A as a novel TAM molecule expressed in vivo by TAM in mammary
      carcinoma and malignant melanoma. In vitro, Ms4a8a mRNA and MS4A8A protein
      expression was strongly induced in bone marrow-derived macrophages (BMDMs) by
      combining M2 mediators (IL-4, glucocorticoids) and tumor-conditioned media (TCM).
      Admixture of MS4A8A(+) TCM/IL-4/GC-treated BMDM significantly enhanced the tumor
      growth rate of subcutaneously transplanted TS/A mammary carcinomas. Upon forced
      overexpression of MS4A8A, Raw 264.7 macrophage-like cells displayed a special
      gene signature. Admixture of these MS4A8A(+) Raw 264.7 cells also significantly
      enhanced the tumor growth rate of subcutaneously transplanted mammary carcinomas.
      To identify the signaling pathways involved in synergistic induction of MS4A8A,
      the major signaling cascades with known functions in TAM were analyzed. Although
      inhibitors of NF-kappaB activation and of the MAPK JNK and ERK did not show
      relevant effects, the p38alpha/beta MAPK inhibitor SB203580 strongly and highly
      significantly (p > 0.001) inhibited MS4A8A expression on mRNA and protein level.
      In addition, MS4A8A expression was restricted in M2 BMDM from mice with defective
      GC receptor (GR) dimerization indicating that classical GR gene regulation is
      mandatory for MS4A8A induction. In conclusion, expression of MS4A8A within the
      complex signal integration during macrophage immune responses may act to fine
      tune gene regulation. Furthermore, MS4A8A(+) TAM may serve as a novel cellular
      target for selective cancer therapy.

PMID- 20824699
TI  - Curcumin decreases cholangiocarcinogenesis in hamsters by suppressing
      inflammation-mediated molecular events related to multistep carcinogenesis.
AB  - Cholangiocarcinoma (CCA) is a highly metastatic tumor linked to liver fluke
      infection and consumption of nitrosamine-contaminated foods and is a major health
      problem especially in South-Eastern Asia. In search for a suitable
      chemopreventive agents, we investigated the effect of curcumin, a traditional
      anti-inflammatory agent derived from turmeric (Curcuma longa), on CCA development
      in an animal model by infection with the liver fluke Opisthorchis viverrini and
      administration of N-nitrosodimethylamine and fed with curcumin-supplemented diet.
      The effect of curcumin-supplemented diet on histopathological changes and
      survival were assessed in relation to NF-kappaB activation, and the expression of
      NF-kappaB-related gene products involved in inflammation, DNA damage, apoptosis,
      cell proliferation, angiogenesis and metastasis. Our results showed that dietary
      administration of this nutraceutical significantly reduced the incidence of CCA
      and increased the survival of animals. This correlated with the suppression of
      the activation of transcription factors including NF-kappaB, AP-1 and STAT-3, and
      reduction in the expression of proinflammatory proteins such as COX-2 and iNOS.
      The formation of iNOS-dependent DNA lesions (8-nitroguanine and 8-oxo-7,8-dihydro
      2'-deoxyguanosine) was inhibited. Curcumin suppressed the expression of proteins
      related to cell survival (bcl-2 and bcl-xL), proliferation (cyclin D1 and c-myc),
      tumor invasion (MMP-9 and ICAM-1) and angiogenesis (VEGF), and microvessel
      density. Induction of apoptotic events as indicated by caspase activation and
      PARP cleavage was also noted. Our results suggest that curcumin exhibits an
      anticarcinogenic potential via suppression of various events involved in multiple
      steps of carcinogenesis, which is accounted for by its ability to suppress
      proinflammatory pathways.

PMID- 20824700
TI  - Farnesyl transferase inhibitor treatment of breast cancer cells leads to altered
      RhoA and RhoC GTPase activity and induces a dormant phenotype.
AB  - Farnesyl transferase inhibitors (FTIs) were shown to be effective in modulating
      tumor growth in Ras-transformed tumor cells. Recent studies have focused on Rho
      GTPases as putative targets of FTI action. Previously, we demonstrated that FTIs
      were effective in inhibiting the growth and invasiveness of RhoC GTPase
      overexpressing inflammatory breast cancer (IBC) cells however, RhoC activity was
      increased. In this study, we examine the mechanisms of FTI action on breast
      cancer cells in culture through modulation of RhoC and RhoA GTPases. We found
      that FTI inhibition of breast cancer cell growth was reversible and resembled
      what has been described for an in vitro model of tumor cell dormancy. On FTI
      treatment, levels of active RhoA decreased significantly, whereas levels of
      active RhoC increased 3.8-fold. We studied the role of these two GTPases in a
      fibronectin and basic FGF-induced model of breast cancer cell dormancy.
      Hypoactivation of RhoA and hyperactivation of RhoC were seen to induce morphology
      and growth changes consistent with tumor cell dormancy in culture. In addition,
      the JNK/SAPK pathway was induced on FTI treatment. A pharmacologic inhibitor of
      the JNK/SAPK pathway significantly reduced the number of dormant cells. This
      study has implications for the use of FTIs as therapeutic agents as well as
      potential mechanisms for breast cancer cell dormancy.

PMID- 20824701
TI  - Recent trends in colorectal cancer mortality in Europe.
AB  - Colorectal cancer mortality has been declining over the last two decades in
      Europe, particularly in women, the trends being, however, different across
      countries and age groups. We updated to 2007 colorectal cancer mortality trends
      in Europe using data from the World Health Organization (WHO). Rates were
      analyzed for the overall population and separately in young, middle-age and
      elderly populations. In the European Union (EU), between 1997 and 2007 mortality
      from colorectal cancer declined by around 2% per year, from 19.7 to 17.4/100,000
      men (world standardized rates) and from 12.5 to 10.5/100,000 women. Persisting
      favorable trends were observed in countries of western and northern Europe, while
      there were more recent declines in several countries of eastern Europe, including
      the Czech Republic, Hungary and Slovakia particularly in women (but not Romania
      and the Russian Federation). In 2007, a substantial excess in colorectal cancer
      mortality was still observed in Slovakia, Hungary, Croatia, the Czech Republic
      and Slovenia in men (rates over 25/100,000), and in Hungary, Norway, Denmark and
      Slovakia in women (rates over 14/100,000). Colorectal mortality trends were more
      favorable in the young (30-49 years) from most European countries, with a decline
      of ~2% per year since the early 1990s in both men and women from the EU. The
      recent decreases in colorectal mortality rates in several European countries are
      likely due to improvements in (early) diagnosis and treatment, with a consequent
      higher survival from the disease. Interventions to further reduce colorectal
      cancer burden are, however, still warranted, particularly in eastern European
      countries.

PMID- 20824702
TI  - High constant incidence rates of second primary cancers of the head and neck: a
      pooled analysis of 13 cancer registries.
AB  - Scanty data are available on the incidence (i.e., the absolute risk) of second
      cancers of the head and neck (HN) and its pattern with age. We investigated this
      issue using data from a multicentric study of 13 population-based cancer
      registries from Europe, Canada, Australia and Singapore for the years 1943-2000.
      A total of 99,257 patients had a first primary HN cancer (15,985 tongue, 22,378
      mouth, 20,758 pharyngeal, and 40,190 laryngeal cancer), contributing to 489,855
      person-years of follow-up. A total of 1,294 of the patients (1.3%) were diagnosed
      with second HN cancers (342 tongue, 345 mouth, 418 pharynx and 189 larynx). Male
      incidence rates of first HN cancer steeply increased from 0.68/100,000 at age 30
      34 to 46.2/100,000 at age 70-74, and leveled off at older age; female incidence
      increased from 0.50/100,000 at age 30-34 to 16.5/100,000 at age 80-84. However,
      age-specific incidence of second HN cancers after a first HN cancer in men was
      around 200-300/100,000 between age 40-44 and age 70-74 and tended to decline at
      subsequent ages (150/100,000 at age 80-84); in women, incidence of second HN
      cancers was around 200-300/100,000 between age 45-49 and 80-84. The patterns of
      age-specific incidence were consistent for different subsites of second HN cancer
      and sexes; moreover, they were similar for age-specific incidence of first
      primary HN cancer in patients who subsequently developed a second HN cancer. The
      incidence of second HN cancers does not increase with age, but remains constant,
      or if anything, decreases with advancing age.

PMID- 20824703
TI  - Integrated genetic and epigenetic analysis of bladder cancer reveals an additive
      diagnostic value of FGFR3 mutations and hypermethylation events.
AB  - The bladder cancer genome harbors numerous oncogenic mutations and aberrantly
      methylated gene promoters. The aim of our study was to generate a profile of
      these alterations and investigate their use as biomarkers in urine sediments for
      noninvasive detection of bladder cancer. We systematically screened FGFR3,
      PIK3CA, TP53, HRAS, NRAS and KRAS for mutations and quantitatively assessed the
      methylation status of APC, ARF, DBC1, INK4A, RARB, RASSF1A, SFRP1, SFRP2, SFRP4,
      SFRP5 and WIF1 in a prospective series of tumor biopsies (N = 105) and urine
      samples (N = 113) from 118 bladder tumor patients. We also analyzed urine samples
      from 33 patients with noncancerous urinary lesions. A total of 95 oncogenic
      mutations and 189 hypermethylation events were detected in the 105 tumor
      biopsies. The total panel of markers provided a sensitivity of 93%, whereas
      mutation and methylation markers alone provided sensitivities of 72% and 70%,
      respectively. In urine samples, the sensitivity was 70% for all markers, 50% for
      mutation markers and 52% for methylation markers. FGFR3 mutations occurred more
      frequently in tumors with no methylation events than in tumors with one or more
      methylation events (78% vs. 33%; p < 0.0001). FGFR3 mutation in combination with
      three methylation markers (APC, RASSF1A and SFRP2) provided a sensitivity of 90%
      in tumors and 62% in urine with 100% specificity. These results suggest an
      inverse correlation between FGFR3 mutations and hypermethylation events, which
      may be used to improve noninvasive, DNA-based detection of bladder cancer.

PMID- 20824704
TI  - Use of faecal markers in screening for colorectal neoplasia: a European group on
      tumor markers position paper.
AB  - Several randomized controlled trials have shown that population-based screening
      using faecal occult blood testing (FOBT) can reduce mortality from colorectal
      neoplasia. Based on this evidence, a number of countries have introduced
      screening for colorectal cancer (CRC) and high-risk adenoma and many others are
      considering its introduction. The aim of this article is to critically review the
      current status of faecal markers as population-based screening tests for these
      neoplasia. Most of the available faecal tests involve the measurement of either
      occult blood or a panel of DNA markers. Occult blood may be measured using either
      the guaiac faecal occult blood test (gFOBT) or a faecal immunochemical test
      (iFOBT). Although iFOBT may require a greater initial investment, they have
      several advantages over gFOBT, including greater analytical sensitivity and
      specificity. Their use results in improved clinical performance and higher uptake
      rates. Importantly for population screening, some of the iFOBTs can be automated
      and provide an adjustable cutoff for faecal haemoglobin concentration. However,
      samples for iFOBT, may be less stable after collection than for gFOBT. For new
      centres undertaking FOBT for colorectal neoplasia, the European Group on Tumour
      Markers recommends use of a quantitative iFOBT with an adjustable cutoff point
      and high throughput analysis. All participants with positive FOBT results should
      be offered colonoscopy. The panel recommends further research into increasing the
      stability of iFOBT and the development of improved and affordable DNA and
      proteomic-based tests, which reduce current false negative rates, simplify sample
      transport and enable automated analysis.

PMID- 20824706
TI  - Randomized healthservices study of human papillomavirus-based management of low
      grade cytological abnormalities.
AB  - Human papillomavirus (HPV)-based management of women with borderline atypical
      squamous cells of undetermined significance (ASCUS) or mildly abnormal cervical
      intraepithelial neoplasia (CINI) cervical cytology has been extensively studied
      in the research setting. We wished to assess safety and health care resource use
      of a real-life health care policy using HPV triaging. All 15 outpatient clinics
      involved in the organized population-based screening program in Stockholm, Sweden
      screening program were randomized to either continue with prior policy
      (colposcopy of all women with ASCUS/CINI) or to implement a policy with HPV
      triaging and colposcopy only of HPV-positive women. The trial enrolled the 3,319
      women who were diagnosed with ASCUS (n = 1,335) or CINI (n = 1,984) in Stockholm
      during 17th March 2003 to 16th January 2006. Detection of high-grade cervical
      lesions (CINII+) and health care cost consumption was studied by registry
      linkages. The proportion of histopathology-verified CINII+ was similar for the
      two policies (395 of 1,752 women (22.5%; 95% Confidence interval [CI]: 20.6
      24.6%) had CINII+ diagnosed with HPV triaging policy, 318 of 1,567 women (20.3%;
      95%CI: 18.3-22.4%) had CINII+ with colposcopy policy). Sixty-four percent of
      women with ASCUS and 77% of women with CINI were HPV positive. HPV-positivity was
      age-dependent, with 81% of women below 35 years of age and 44% of women above 45
      years of age testing HPV-positive. HPV triaging was cost-effective only above 35
      years of age. In conclusion, a real-life randomized healthservices study of HPV
      triaging of women with ASCUS/CINI demonstrated similar detection of CINII+ as
      colposcopy of all women.

PMID- 20824707
TI  - Cysteinyl leukotriene receptor expression pattern affects migration of breast
      cancer cells and survival of breast cancer patients.
AB  - The fact that breast cancer patients with local or distal dissemination exhibit
      decreased survival, promotes a search for novel mechanisms to suppress such tumor
      progression. Here, we have determined the expression of proinflammatory cysteinyl
      leukotriene receptors (CysLTRs) in breast tumor tissue and their signaling effect
      on breast cancer cell functions related to tumor progression. Patients with
      breast tumors characterized by high CysLT(1)R and low CysLT(2)R expression levels
      exhibited increased risk of cancer-induced death in univariate analysis for both
      the total patient group (hazard ratio [HR] = 2.88, 95% confidence interval [CI] =
      1.11-7.41), as well as patients with large (>20 mm) tumors (HR = 5.08, 95% CI =
      1.39-18.5). Multivariate analysis revealed that patients with large tumors
      exhibiting high CysLT(1)R and low CysLT(2)R expression levels had a significantly
      reduced survival, also when adjusted for established prognostic parameters (HR =
      7.51, 95% CI = 1.83-30.8). In patients with large (>20 mm) tumors, elevated
      CysLT(2)R expression predicted an improved 5-year survival (log-rank test p =
      0.04). Surprisingly, for longer time periods, this prognostic value was lost.
      This disappearance coincided with the termination of hormonal treatment.
      Tamoxifen preserved and even induced transcription of CysLT(2)R, but not
      CysLT(1)R, in estrogene receptor-positive MCF-7 breast cancer cells. This
      elevated CysLT(2)R expression decreased, even below the level of untreated cells,
      when tamoxifen was withdrawn. CysLT(2)R signaling reduced MCF-7 cell migration,
      but had no effect on either proliferation or apoptosis. Our data indicate that
      low CysLT(1)R together with high CysLT(2)R expression levels might be useful
      parameters in prognostication and treatment stratification of breast cancer
      patients.

PMID- 20824705
TI  - Dietary nitrate and nitrite and the risk of thyroid cancer in the NIH-AARP Diet
      and Health Study.
AB  - During the past several decades, an increasing incidence of thyroid cancer has
      been observed worldwide. Nitrate inhibits iodide uptake by the thyroid,
      potentially disrupting thyroid function. An increased risk of thyroid cancer
      associated with nitrate intake was recently reported in a cohort study of older
      women in Iowa. We evaluated dietary nitrate and nitrite intake and thyroid cancer
      risk overall and for subtypes in the National Institutes of Health-American
      Association of Retired Persons (NIH-AARP) Diet and Health Study, a large
      prospective cohort of 490,194 men and women, ages 50-71 years in 1995-1996.
      Dietary intakes were assessed using a 124-item food frequency questionnaire.
      During an average of 7 years of follow-up we identified 370 incident thyroid
      cancer cases (170 men, 200 women) with complete dietary information. Among men,
      increasing nitrate intake was positively associated with thyroid cancer risk
      (relative risk [RR] for the highest quintile versus lowest quintile RR = 2.28,
      95% confidence interval [CI]: 1.29-4.041; p-trend <0.001); however, we observed
      no trend with intake among women (p-trend = 0.61). Nitrite intake was not
      associated with risk of thyroid cancer for either men or women. We evaluated risk
      for the two main types of thyroid cancer. We found positive associations for
      nitrate intake and both papillary (RR = 2.10; 95% CI: 1.09-4.05; p-trend = 0.05)
      and follicular thyroid cancer (RR = 3.42; 95% CI: 1.03-11.4; p-trend = 0.01)
      among men. Nitrite intake was associated with increased risk of follicular
      thyroid cancer (RR = 2.74; 95%CI: 0.86-8.77; p-trend = 0.04) among men. Our
      results support a role of nitrate in thyroid cancer risk and suggest that further
      studies to investigate these exposures are warranted.

PMID- 20824708
TI  - Affinity-matured anti-glycoprotein NMB recombinant immunotoxins targeting
      malignant gliomas and melanomas.
AB  - Glycoprotein NMB (GPNMB), a transmembrane glycoprotein highly expressed in high
      grade gliomas (HGGs), is an attractive target in cancer immunotherapy. We
      isolated a GPNMB-specific scFv clone, G49, from a human synthetic phage-display
      library. To obtain mutant single-chain variable-fragment antibodies (scFvs) with
      improved affinity and immunotoxins with increased activity, we subjected G49 to
      in vitro affinity maturation by a complementarity-determining-region (CDR) random
      mutagenesis technique. Using light-chain CDR3 mutagenesis, cell-based panning by
      phage display, subsequent heavy-chain CDR1 mutagenesis, and flow-cytometric
      selection by yeast-surface display, we generated the mutant scFv clone 902V, with
      an overall 11-fold increase in affinity for GPNMB. Clone 902V was further
      randomized throughout the whole scFv by error-prone PCR, and one mutant, F6V, was
      selected by yeast-surface display. F6V scFv, differing from 902V by one amino
      acid change in the light-chain CDR2, exhibited an affinity for GPNMB of 0.30 nM.
      The F6V mutant scFv clone was fused with a truncated form of Pseudomonas exotoxin
      A to form the immunotoxin F6V-PE38. F6V-PE38 demonstrated significant protein
      synthesis-inhibition activity on GPNMB-expressing glioma and malignant melanoma
      cells (IC(50) = 0.5 ng/ml [8 pM]), a 60-fold improvement over G49 activity, but
      no cytotoxicity on GPNMB-negative cells. Furthermore, F6V-PE38 exhibited
      significant antitumor activity against subcutaneous malignant glioma xenografts
      in two nude-mouse models and a melanoma neoplastic meningitis model in athymic
      rats. These GPNMB-specific scFv antibodies and immunotoxins hold promise as
      reagents in targeted therapy for HGGs and other GPNMB-expressing malignancies.

PMID- 20824709
TI  - Enhancement of a multianalyte serum biomarker panel to identify lymph node
      metastases in non-small cell lung cancer with circulating autoantibody
      biomarkers.
AB  - We recently reported the development of a multianalyte serum algorithm to
      identify nodal status in non-small cell lung cancer (NSCLC) patients facing an
      anatomic resection with curative intent. This study aims to enhance the overall
      performance characteristics of this test by adding autoantibody biomarkers
      identified through immunoproteomic discovery. More specifically, we used sera
      from 20 NSCLC patients to probe 2-D immunoblots of HCC827 lysates for tumor
      associated autoantigens. Relevant differences in immunoreactivity associated with
      pathological nodal status were then identified via tandem mass spectrometry.
      Identified autoantigens were then developed into Luminex immunobead assays
      alongside a series of autoantigen targets relevant to early-disease detection.
      These assays were then used to measure circulating autoantibody levels in the
      identical cohort of NSCLC patients used in our original study. This strategy
      identified 11 autoantigens found primarily in patients with disease progression
      to the locoregional lymph nodes. Custom Luminex-based "direct-capture" assays (25
      total; including autoantibody targets relevant to early-disease detection) were
      assembled to measure autoantibody levels in sera from 107 NSCLC patients.
      Multivariate classification algorithms were then used to identify the optimal
      combination of biomarkers when considered collectively with our original 6
      analyte serum panel. The new algorithm resulting from this analysis consists of
      TNF-alpha, TNF-RI, MIP-1alpha and autoantibodies against Ubiquilin-1,
      hydroxysteroid-(17-beta)-dehydrogenase, and triosephosphate isomerase. The
      inclusion of autoantibody biomarkers provided a dramatic improvement in the
      overall test performance characteristics, relative to the original test panel,
      including an 11% improvement in the classification efficiency.

PMID- 20824710
TI  - Forced expression of Sox21 inhibits Sox2 and induces apoptosis in human glioma
      cells.
AB  - Numerous studies support a role for Sox2 to keep stem cells and progenitor cells
      in an immature and proliferative state. Coexpression of Sox2 and GFAP has been
      found in regions of the adult brain where neural stem cells are present and in
      human glioma cells. In our study, we have investigated the roles of Sox2 and its
      counteracting partner Sox21 in human glioma cells. We show for the first time
      that Sox21 is expressed in both primary glioblastoma and in human glioma cell
      lines. We found that coexpression of Sox2, GFAP and Sox21 was mutually exclusive
      with expression of fibronectin. Our result suggests that glioma consists of at
      least two different cell populations: Sox2(+) /GFAP(+) /Sox21(+) /FN(-) and Sox2(
      ) /GFAP(-) /Sox21(-) /FN(+) . Reduction of Sox2 expression by using siRNA against
      Sox2 or by overexpressing Sox21 using a tetracycline-regulated expression system
      (Tet-on) caused decreased GFAP expression and a reduction in cell number due to
      induction of apoptosis. We suggest that Sox21 can negatively regulate Sox2 in
      glioma. Our findings imply that Sox2 and Sox21 may be interesting targets for the
      development of novel glioma therapy.

PMID- 20824711
TI  - PRKAR1A is overexpressed and represents a possible therapeutic target in human
      cholangiocarcinoma.
AB  - The protein kinase A regulatory subunit 1 alpha (PRKAR1A/PKAI) pathway is
      overexpressed in varieties of tumors and cancer cell lines including
      cholangiocarcinoma (CCA), although its role in CCA growth modulation is unclear.
      In our study, we evaluated the effect of PRKAR1A/PKAI targeting on CCA cell
      proliferation. Real-time PCR demonstrated an increased mRNA expression of
      PRKAR1A/PKAI, whereas protein kinase A regulatory subunit 2 beta (PRKAR2B/PKAII)
      was downregulated in human CCA tissues and CCA cell lines. Immunohistochemistry
      of human CCA tissues revealed increased PRKAR1A with decreased PRKAR2B protein
      expression. Moreover, CCA cell lines showed abundantly expressed PRKAR1A, while
      lacking PRKAR2B expression. Silencing PRKAR1A expression induced growth
      inhibition and apoptosis of CCA cells, with an associated decrease in mitogen
      activated protein kinases, PI3K/Akt, JAK/STAT and Wnt/beta-catenin pathway
      signaling. The inhibition of PKA using a PKA inhibitor and cAMP analogs also led
      to a significant cell growth inhibition. In conclusion, our study reports the
      overexpression as well as molecular mechanisms by which PRKAR1A/PKA regulates
      human CCA cell growth. Importantly, abrogation of gene expression caused
      significant CCA cell growth inhibition, oncogenic signaling and coupled apoptosis
      induction, suggesting PRKAR1A's potential as a drug target for CCA therapy.

PMID- 20824712
TI  - OCT4B1, a novel spliced variant of OCT4, is highly expressed in gastric cancer
      and acts as an antiapoptotic factor.
AB  - The octamer-binding transcription factor 4 (OCT4) is involved in regulating
      pluripotency and self-renewal maintenance of embryonic stem cells. Recently,
      misexpression of OCT4 has been also reported in some adult stem as well as cancer
      cells; a finding which is still controversial. In addition to the previously
      described spliced variants of the gene (e.g., OCT4A and OCT4B), we have recently
      identified a novel variant of the gene, designated as OCT4-B1. In this study, we
      investigated a potential expression and function of OCT4B1 in a series of gastric
      cancer tissues and a gastric adenocarcinoma cell line, AGS. Using the Taqman real
      time PCR approach, we have detected the expression of OCT4B1 in tumors with no or
      much lower expression in marginal samples of the same patients (p < 0.002). We
      have also analyzed the effects of OCT4B1 knock-down in AGS cell line treated with
      specific siRNA directed toward OCT4B1. Our data revealed that interfering with
      the expression of OCT4B1 caused profound changes in the morphology and cell cycle
      distribution of the cells. Furthermore, down-regulation of OCT4B1 significantly
      elevated the relative activity of caspase-3/caspase-7 and the rate of apoptosis
      in the cells (more than 30%). All together, our findings suggest that OCT4B1 has
      a potential role in tumorigenesis of gastric cancer and candidates the variant as
      a new tumor marker with potential value in diagnosis and treatment of gastric
      cancer.

PMID- 20824713
TI  - Prospective assessment of quality of life in long-term ovarian cancer survivors.
AB  - The objective of our study was to compare prospectively the QoL in long-term
      ovarian cancer survivors with short-term survivors and to explore discriminating
      variables between short-term and long-term survival. Thirty-three patients were
      included, 22 died within 5 years post diagnosis and 11 survived beyond 10 years.
      QoL data were collected pre-treatment (baseline), 1-year post diagnoses and for
      long-term survivors 10 years post-treatment using the EORTC QLQ-C30. At baseline,
      there was no difference in terms of FIGO stage, residual tumor and adjuvant
      chemotherapy. Significantly, more short-term survivors (96%) had intra operative
      ascites as compared to long-term survivors (55%) (p = 0.01). Before treatment,
      short-term survivors had clinically significantly lower QoL scores on the
      physical functioning (mean 75.45) and role functioning scale (mean 68.94)
      compared to long-term survivors (mean 68.94 and 84.85, respectively). They also
      reported higher levels of symptoms. One year post-diagnosis, QoL scores were
      comparable in most domains. Long-term survivors had a significantly better global
      QoL but more insomnia. Emotional functioning and global QoL/health status
      improved significantly from baseline to 1-year post-diagnosis and remained
      relatively stable at the 10-year follow-up. The presence of intra operative
      ascites and a supporting social network were identified as significant variables
      that discriminated between short-term and long-term survival. Compared to a
      reference sample, long-term survivors showed similar QoL scores but more
      dyspnoea. Although ovarian cancer patients do not belong to the most prevalent
      survivor populations, we found that long-term survivors have QoL scores similar
      to females without a history of cancer.

PMID- 20824714
TI  - Identification of frequently mutated genes with relevance to nonsense mediated
      mRNA decay in the high microsatellite instability cancers.
AB  - Frameshift mutations at coding mononucleotide repeats (cMNR) are frequent in high
      microsatellite instability (MSI-H) cancers. Frameshift mutations in cMNR result
      in the formation of a premature termination codon (PTC) in the transcribed mRNA,
      and these abnormal mRNAs are generally degraded by nonsense mediated mRNA decay
      (NMD). We have identified novel genes that are frequently mutated at their cMNR
      by blocking NMD in two MSI-H cancer cell lines. After blocking NMD, we screened
      for differentially expressed genes using DNA microarrays, and then used database
      analysis to select 28 candidate genes containing cMNR with more than 9 nucleotide
      repeats. cMNR mutations have not been previously reported in MSI-H cancers for 15
      of the 28 genes. We analyzed the cMNR mutation of each of the 15 genes in 10 MSI
      H cell lines and 21 MSI-H cancers, and found frequent mutations of 12 genes in
      MSI-H cell lines and cancers, but not in microsatellite stable (MSS) cancers.
      Among these genes, the most frequently mutated in MSI-H cell lines were MLL3
      (70%), PHACTR4 (70%), RUFY2 (50%) and TBC1D23 (50%). MLL3, which has already been
      implicated in cancer, had the highest mutation frequency in MSI-H cancers (48%).
      Our combined approach of NMD block, database search, and mutation analysis has
      identified a large number of genes mutated in their cMNR in MSI-H cancers. The
      identified mutations are expected to contribute to MSI-H tumorigenesis by causing
      an absence of gene expression or low gene dosage effects.

PMID- 20824715
TI  - Tumor-reactive CD4+ CD8alphabeta+ CD103+ alphabetaT cells: a prevalent tumor
      reactive T-cell subset in metastatic colorectal cancers.
AB  - High level of T-cell infiltration in colorectal carcinomas (CRCs) is a good
      prognostic indicator, but the tumor reactivity of this infiltrate (tumor
      infiltrating lymphocytes [TIL]) is poorly documented. This study examined the
      presence, phenotype and functional features of tumor-reactive lymphocytes in
      human CRC. Freshly dissociated TIL and T cell lines were isolated from CRC
      samples and from some paired normal colonic mucosa. Four tumor cell lines were
      obtained. Autologous tumor reactivity of CRC TIL and tumor-reactive cell features
      were analyzed. We demonstrate the presence among CRC TIL of variable fractions
      (up to 18%) of double positive CD4(+) CD8alphabeta(+) (DP) alphabeta T cells.
      Interestingly, a high proportion (16-20%) of this TIL subset displayed tumor
      reactivity, whilst this was the case for no or few single positive TIL. Low
      levels of DP TIL were found in most CRC samples and in normal colonic mucosa, but
      these cells were higher in metastatic CRC. Furthermore, we showed that DP TIL
      were polyclonal, restricted by HLA class-I, proliferated poorly and secreted
      higher amounts of IL-4 and IL-13 than single positive T cells, on cognate or CD3
      stimulation. DP CRC TIL also expressed CD103, confirming their mucosal origin.
      Increased frequencies of tumor-reactive DP TIL in metastatic CRC suggest that
      these cells play a role in the metastatic process of this cancer. Based on their
      high secretion of IL-4 and IL-13 and on previously described roles of these
      cytokines in cancers, we postulate that DP TIL could favor CRC growth or
      metastasis and/or downmodulate immune responses to these tumors.

PMID- 20824716
TI  - EGFR and HER3 mRNA expression levels predict distant metastases in locally
      advanced rectal cancer.
AB  - Aberrant activation of the HER signaling pathways plays a critical role in the
      invasive and metastatic potential of tumors. The aim of this study was to address
      whether, in rectal cancer, alterations of these pathways could have a value as
      prognostic factors to be used to identify patients who are at risk of distant
      metastases. Therefore, the mRNA expression of the four members of the HER family
      as well as the frequency of PTEN allelic loss and KRAS/BRAF mutations were
      determined in pretreatment biopsies from a series of 100 locally advanced rectal
      cancers and then their ability to predict distant metastases was evaluated. Over
      expression of EGFR (p = 0.021), HER2 (p = 0.011) and HER3 (p = 0.020) was
      significantly associated with worse metastasis-free survival in univariate
      analysis. In multivariate analysis, both over-expression of EGFR (p = 0.028) and
      HER3 (p = 0.011) remained independent prognostic factors for distant metastasis.
      In conclusion, quantification of EGFR and HER3 mRNA expression in pretreatment
      biopsies may be useful to identify patients who are at risk of developing
      metastases.

PMID- 20824717
TI  - Cell type-dependent biomarker expression in adenoid cystic carcinoma: biologic
      and therapeutic implications.
AB  - BACKGROUND: Adenoid cystic carcinoma (ACC), a rare and progressive salivary
      malignancy, is characterized by cellular, morphologic, and clinical
      heterogeneity. The authors of this report hypothesized that the dual cellular
      composition of ACC plays an important role in biomarker evaluation, tumor
      biologic behavior, and response to therapy. METHODS: To investigate the
      differential localization and expression of the c-Kit protein and the epidermal
      growth factor receptor (EGFR) protein, immunohistochemical analyses were
      performed on tissue arrays that were constructed from 199 tumors, and the results
      were correlated with clinicopathologic factors. RESULTS: c-Kit expression was
      limited to the inner ductal epithelial cells, whereas EGFR expression was limited
      mainly to the outer myoepithelial cells in the majority of ACCs with tubular and
      cribriform patterns. In solid ACCs, c-Kit uniformly was positive, whereas EGFR
      consistently was negative. A significant statistical correlation was observed
      between c-Kit expression and a poor 3-year outcome, and EGFR expression was
      correlated with a better 3-year outcome. CONCLUSIONS: The current findings
      underscored the importance of cellular subtype localization of biomarkers in the
      clinical and therapeutic stratification of patients with ACC.

PMID- 20824718
TI  - Socioeconomic factors associated with adjuvant hormone therapy use in older
      breast cancer survivors.
AB  - BACKGROUND: The authors sought to identify socioeconomic (SES) factors associated
      with adjuvant hormone therapy (HT) use among a contemporary population of older
      breast cancer survivors. METHODS: Telephone surveys were conducted among women
      (ages 65-89 years) residing in 4 states (California, Florida, Illinois, and New
      York) who underwent initial breast cancer surgery in 2003. Demographic, SES, and
      treatment information was collected. RESULTS: Of 2191 women, 67% received
      adjuvant HT with either tamoxifen or an aromatase inhibitor (AI); 71% of those
      women were on an AI. When adjusting for multiple demographic and SES factors,
      predictors of HT use were better education (high school degree or higher), better
      informational/emotional support, and younger age (ages 65-79 years).
      Race/ethnicity, income, and insurance coverage for medication costs were not
      associated with receiving HT. For those on HT, when adjusting for all other
      factors, women were more likely to receive an AI if they had insurance coverage
      for some or all medication costs, if they were wealthier, if they had better
      informational/emotional support, and if they were younger (ages 65-69 years).
      CONCLUSIONS: The majority of older women in this population-based cohort received
      adjuvant HT, and the adoption of AIs was early. The results indicted that
      providers should be aware that a woman's education level and support system
      influence her decision to take HT. Given the high cost of AIs, their benefits in
      postmenopausal women with hormone receptor-positive breast cancer, and the
      current finding that women with no insurance coverage for medication costs were
      significantly less likely to receive an AI, we recommend that policymakers
      address this issue.

PMID- 20824719
TI  - Treatment recommendations for primary extradural meningiomas.
AB  - Primary extradural meningiomas (PEMs) represent about 2% of all meningiomas and
      are often encountered by non-neurosurgeons. These lesions typically present as
      enlarging, painless, benign masses that can be surgically cured. Imaging is
      critical for defining involvement of adjacent structures; however, diagnosis
      depends on classic histologic patterns. Treatment for benign PEMs (WHO I)
      consists of resection with wide margins, whereas adjuvant therapy after resection
      of atypical (WHO II) or malignant (WHO III) PEMs should be considered. By using
      the collective experience from our comprehensive cancer center, including neuro
      oncologists, neuroradiologists, and neurosurgeons, in addition to a complete
      literature review, the authors have established treatment guidelines not
      previously reported. This manuscript describes key features of these challenging
      tumors to aid in diagnosis, presents the largest published review of all reported
      PEMs (n = 163), and provides salient treatment guidelines to surgeons unfamiliar
      with these challenging tumors.

PMID- 20824720
TI  - Molecular predictors of outcome in a phase 3 study of gemcitabine and erlotinib
      therapy in patients with advanced pancreatic cancer: National Cancer Institute of
      Canada Clinical Trials Group Study PA.3.
AB  - BACKGROUND: National Cancer Institute of Canada Clinical Trials Group PA.3 (NCIC
      CTG PA.3) was a phase 3 study (n = 569) that demonstrated benefits for overall
      survival and progression-free survival with the addition of the epidermal growth
      factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib to gemcitabine
      in patients with advanced pancreatic carcinoma (APC). Mutation status of the v-Ki
      ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and EGFR gene copy number
      (GCN) were evaluated as predictive markers in 26% of patients who had tumor
      samples available for analysis. METHODS: KRAS mutation status was evaluated by
      direct sequencing of exon 2, and EGFR GCN was determined by fluorescence in situ
      hybridization (FISH) analysis. The results were correlated with survival, which
      was the primary endpoint of the trial. RESULTS: KRAS analysis was successful in
      117 patients, and EGFR FISH analysis was successful in 107 patients. KRAS
      mutations were identified in 92 patients (78.6%), and EGFR amplification or high
      polysomy (FISH-positive results) was identified in 50 patients (46.7%). The
      hazard ratio of death between gemcitabine/erlotinib and gemcitabine/placebo was
      0.66 (95% confidence interval [CI], 0.28-1.57) for patients with wild-type KRAS
      and 1.07 (95% CI, 0.68-1.66) for patients with mutant KRAS (P value for
      interaction = .38), and the hazard ratio was 0.6 (95% CI, 0.34-1.07) for FISH
      negative patients and 0.90 (95% CI, 0.49-1.65) for FISH-positive patients (P
      value for interaction = .32). CONCLUSIONS: In a molecular subset analysis of
      patients from NCIC CTG PA.3, EGFR GCN and KRAS mutation status were not
      identified as markers predictive of a survival benefit from the combination of
      erlotinib with gemcitabine for the first-line treatment of APC.

PMID- 20824722
TI  - Change in defense mechanisms and coping over the course of short-term dynamic
      psychotherapy for adjustment disorder.
AB  - Short-term dynamic psychotherapy (STDP) has rarely been investigated with regard
      to its underlying mechanisms of change, even if psychoanalytic theory informs us
      about several potential putative mechanisms of change in patients. Change in
      overall defensive functioning is one. In this study, we explored the role of
      overall defensive functioning, by comparing it on the process level with the
      neighbouring concept of overall coping functioning. A total of N=32 patients,
      mainly presenting adjustment disorder, were included in the study. The patients
      underwent STDP up to 40 sessions; three sessions per psychotherapy were
      transcribed and analyzed by using two observer-rating scales: Defense Mechanism
      Rating Scales (Perry, 1990) and Coping Action Patterns (Perry, Drapeau, Dunkley,
      & Blake, 2005). Hierarchical linear modeling was applied to model the change over
      the course of therapy and relate it to outcome. Results suggest that STDP has an
      effect on the target variable of overall defensive functioning, which was absent
      for overall coping functioning. Links with outcome confirm the importance of the
      effect. These results are discussed from methodological and clinical viewpoints.

PMID- 20824721
TI  - Clinical and molecular features of papillary thyroid cancer in adolescents and
      young adults.
AB  - BACKGROUND: Age disparities in thyroid cancer incidence and outcome among
      adolescents and young adults (AYAs) with thyroid cancer are under reported. In
      this study, the authors compared the molecular and clinical features of papillary
      thyroid cancer (PTC) in AYAs with the same features among patients in other age
      groups. METHODS: One thousand eleven patients underwent initial treatment for PTC
      at the University of California at San Francisco. Patients were subdivided into 2
      age groups: ages 15 to 39 years (the AYA group) and aged >=40 years. Demographic,
      clinical, and survival data in the cohort also were compared with data from the
      National Cancer Instsitute's Surveillance, Epidemiology, and End Results (SEER)
      Program. In a subset of the study cohort, the primary tumors were analyzed by
      genome-wide expression analyses, genotyping for common somatic mutations, and
      pathway-specific gene expression arrays between the age groups. RESULTS: The
      percentage of women and the lymph node metastasis rate were significantly higher
      in the AYA group. In the AYA group, the rate of distant metastasis was lower.
      Disease-free survival and median overall survival were significantly higher in
      the AYA group. The better survival in AYA patients also was apparent in the
      national SEER data. An unsupervised cluster analysis of gene expression data
      revealed no distinct clustering by age in 96 PTC samples. The frequency and type
      of somatic mutations in the primary tumors did not differ significantly between
      age groups (the AYA group vs the group aged >=40 years). Six genes (extracellular
      matrix protein 1 [ECM1], v-erb-2 erythroblastic leukemia viral oncogene homolog 2
      [ERBB2], urinary plasminogen activator [UPA], 6-phosphofructo-2-kinase/fructose
      2,6-biphosphatase 2 [PFKFB2], meis homeobox 2 [MEIS2], and carbonic anhydrase II
      [CA2]) had significant differential expression between age groups. CONCLUSIONS:
      The extent of disease at presentation and the survival of patients with PTC
      differed between AYAs and older patients. The current results indicated that
      these differences may be caused by several candidate genes and that these genes
      are expressed differentially and may play an important role in tumor cell
      biology. However, no distinct gene expression profiles exist for patients with
      PTC that distinguish between AYAs and patients aged >=40 years.

PMID- 20824723
TI  - Hierarchical relational binding in the medial temporal lobe: the strong get
      stronger.
AB  - Controversy exists over the functional role of the medial temporal lobe (MTL) in
      episodic memory. Some have suggested that the hippocampus plays a unique and
      qualitatively different role than other MTL regions, whereas others suggest that
      the entire MTL has one functional role, which is to support the consolidation of
      declarative memories. Hierarchical relational binding theory (hRBT) purports that
      the functional role of the entire MTL is the binding of features associated with
      an episodic experience. As the hippocampus sits at the top of this hierarchy,
      binding at this level is particularly efficient in reinstating event features at
      the time of retrieval. Thus, this theory offers a unified account of MTL that
      yields outcomes similar to theories that suggest a special role of the
      hippocampus. In this way, hRBT captures features of both single- and dual-process
      models of MTL and reconciles controversies about the nature of episodic
      recollection.

PMID- 20824724
TI  - First-line chemotherapy with capecitabine and temozolomide in patients with
      metastatic pancreatic endocrine carcinomas.
AB  - BACKGROUND: Temozolomide is an active agent in metastatic pancreatic endocrine
      carcinomas. In vitro data indicate that the combination of capecitabine and
      temozolomide is synergistic for induction of apoptosis in neuroendocrine tumor
      cell lines. The authors retrospectively evaluated the efficacy of capecitabine
      and temozolomide in 30 patients with metastatic pancreatic endocrine carcinomas
      to assess response rate, progression free survival (PFS), and overall survival
      (OS). METHODS: Patients with metastatic, well, or moderately differentiated
      pancreatic endocrine carcinomas who had not received prior systemic chemotherapy
      were treated with capecitabine (750 mg/m2 twice daily, days 1-14) and
      temozolomide (200 mg/m2 once daily, days 10-14) every 28 days. RESULTS: Among 30
      patients treated, 21 (70%) patients achieved an objective radiographic response.
      Median progression-free survival was 18 months. The rate of survival at two years
      was 92%. Only 4 patients (12%) experienced grade 3 or 4 adverse events.
      CONCLUSIONS: The combination of capecitabine and temozolomide is associated with
      an exceptionally high and durable response rate in metastatic endocrine
      carcinomas of the pancreas. Clinical endpoints, including response rate,
      survival, and toxicity, are superior to those observed with streptozocin-based
      regimens.

PMID- 20824725
TI  - L-asparaginase treatment in acute lymphoblastic leukemia: a focus on Erwinia
      asparaginase.
AB  - Asparaginases are a cornerstone of treatment protocols for acute lymphoblastic
      leukemia (ALL) and are used for remission induction and intensification treatment
      in all pediatric regimens and in the majority of adult treatment protocols.
      Extensive clinical data have shown that intensive asparaginase treatment improves
      clinical outcomes in childhood ALL. Three asparaginase preparations are
      available: the native asparaginase derived from Escherichia coli (E. coli
      asparaginase), a pegylated form of this enzyme (PEG-asparaginase), and a product
      isolated from Erwinia chrysanthemi, ie, Erwinia asparaginase. Clinical
      hypersensitivity reactions and silent inactivation due to antibodies against E.
      coli asparaginase, lead to inactivation of E. coli asparaginase in up to 60% of
      cases. Current treatment protocols include E. coli asparaginase or PEG
      asparaginase for first-line treatment of ALL. Typically, patients exhibiting
      sensitivity to one formulation of asparaginase are switched to another to ensure
      they receive the most efficacious treatment regimen possible. Erwinia
      asparaginase is used as a second- or third-line treatment in European and US
      protocols. Despite the universal inclusion of asparaginase in such treatment
      protocols, debate on the optimal formulation and dosage of these agents
      continues. This article provides an overview of available evidence for optimal
      use of Erwinia asparaginase in the treatment of ALL.

PMID- 20824726
TI  - Functional convergence of developmentally and adult-generated granule cells in
      dentate gyrus circuits supporting hippocampus-dependent memory.
AB  - In the hippocampus, the production of dentate granule cells (DGCs) persists into
      adulthood. As adult-generated neurons are thought to contribute to hippocampal
      memory processing, promoting adult neurogenesis therefore offers the potential
      for restoring mnemonic function in the aged or diseased brain. Within this
      regenerative context, one key issue is whether developmentally generated and
      adult-generated DGCs represent functionally equivalent or distinct neuronal
      populations. To address this, we labeled separate cohorts of developmentally
      generated and adult-generated DGCs and used immunohistochemical approaches to
      compare their integration into circuits supporting hippocampus-dependent memory
      in intact mice. First, in the water maze task, rates of integration of adult
      generated DGCs were regulated by maturation, with maximal integration not
      occurring until DGCs were five or more weeks in age. Second, these rates of
      integration were equivalent for embryonically, postnatally, and adult-generated
      DGCs. Third, these findings generalized to another hippocampus-dependent task,
      contextual fear conditioning. Together, these experiments indicate that
      developmentally generated and adult-generated DGCs are integrated into
      hippocampal memory networks at similar rates, and suggest a functional
      equivalence between DGCs generated at different developmental stages.

PMID- 20824727
TI  - Hippocampal subregions differentially associate with standardized memory tests.
AB  - Recent studies suggest that individual hippocampal subregions perform distinct
      cognitive operations and are differentially targeted by aging and disease.
      Although originally developed to assess global hippocampal function, whether
      performance on standard memory tests used in neuropsychological batteries is
      associated with individual hippocampal subregions remains unknown. Here we
      addressed this issue by imaging 210 neuropsychologically characterized subjects
      using a high-resolution variant of functional magnetic resonance imaging that
      generates maps reflective of basal hippocampal metabolism. Regression analysis
      revealed memory tests that differentially associate with two hippocampal
      subregions, the entorhinal cortex (EC) and the dentate gyrus (DG). Whereas
      performance on the delayed retention component of the Selective Reminding Test
      was associated with the EC, performance on the recognition component of the
      Benton Visual Retention Test (BVRT) was associated with the DG. Furthermore,
      elevation in blood glucose, previously shown to target the DG, was found to
      correlate selectively with the recognition component of the BVRT. These findings
      provide further evidence that the hippocampal subregions perform distinct roles,
      and, interpreted in the context of previous neuropsychological and imaging
      studies, confirm that aging and Alzheimer's disease target different hippocampal
      subregions.

PMID- 20824728
TI  - LTP- and LTD-inducing stimulations cause opposite changes in arc/arg3.1 mRNA
      level in hippocampal area CA1 in vivo.
AB  - Immediate early genes (IEGs) typically are the first genetic responders to a
      variety of cellular activations. The IEG that encodes activity-regulated
      cytoskeleton-associated protein (arc/arg3.1) has attracted much interest because
      its mRNA is transported to and translated near activated synapses. Moreover, arc
      has been implicated in both long-term potentiation (LTP) and long-term depression
      (LTD). However, little is known about the time course of altered arc expression
      during LTP and LTD. Here we characterized arc mRNA levels in area CA1 of the
      adult rat hippocampus in vivo after LTP- and LTD-inducing stimulations that were
      identical, except for the temporal patterning of the stimulation pulses. We
      observed a persistent increase in arc mRNA level during LTP. In contrast, during
      LTD, arc mRNA level first was decreased and then transiently increased relative
      to control level. These findings demonstrate that arc mRNA is regulated
      differently during LTP and LTD, and they provide evidence for stimulation-induced
      downregulation of mRNA availability during LTD. Findings of abbreviated LTD when
      transcription was inhibited indicate that the prolonged maintenance of the type
      of N-methyl-D-aspartate receptor-dependent LTD studied here requires de novo
      transcription. Furthermore, lack of evidence for a LTD-associated change in the
      mRNA level of the IEG zif268 demonstrates that the decrease in arc mRNA during
      LTD is not a general genetic response. Thus, the regulation of arc expression not
      only differs between LTP and LTD, but also diverges from that of other IEGs
      implicated in activity-dependent synaptic plasticity.

PMID- 20824729
TI  - Protein phosphatases 1 and 2A are both required for long-term depression and
      associated dephosphorylation of cAMP response element binding protein in
      hippocampal area CA1 in vivo.
AB  - Evidence shows that the serine/threonine protein phosphatase 1 (PP1) plays a
      critical role in synaptic plasticity and memory. Little is known about the
      contribution of the serine/threonine phosphatase 1 (PP2A) to synaptic plasticity.
      Both protein phosphatases can target the transcription factor cAMP response
      element binding protein (CREB), whose phosphorylation at Ser133, we previously
      found, was downregulated during long-term depression (LTD) of glutamatergic
      transmission in area CA1 of the adult hippocampus in vivo. Other work from our
      group showed that the activity of PP2A, as well as that of PP1, is increased
      after LTD induction in area CA1 in vivo. We therefore investigated here whether
      both protein phosphatases are necessary for LTD in area CA1, and whether they
      both are involved in the LTD-associated modification of CREB. We found that
      inhibition of either PP1 or PP2A interferes with the establishment of LTD.
      Furthermore, inhibition of either enzyme alone abrogated the LTD-associated
      dephosphorylation of CREB. Interestingly, inhibition of PP1 disrupted CREB
      dephosphosphorylation rapidly after LTD-inducing stimulation, whereas inhibition
      of PP2A did not blunt the CREB modification until a later time point. Thus, both
      PP1 and PP2A regulate CREB during LTD in area CA1, although possibly through
      different signaling pathways. Our results demonstrate that PP2A, similar to PP1,
      plays an essential role in the molecular events that underlie LTD at
      glutamatergic synapses in hippocampal area CA1 in vivo. We propose that one of
      the mechanisms through which these protein phosphatases may contribute to the
      prolonged maintenance of LTD is through the regulation of CREB.

PMID- 20824731
TI  - Exercise increases insulin signaling in the hippocampus: physiological effects
      and pharmacological impact of intracerebroventricular insulin administration in
      mice.
AB  - Increasing evidence indicates that physical exercise induces adaptations at the
      cellular, molecular, and systemic levels that positively affect the brain.
      Insulin plays important functional roles within the brain that are mediated by
      insulin-receptor (IR) signaling. In the hippocampus, insulin improves synaptic
      plasticity, memory formation, and learning via direct modulation of GABAergic and
      glutamatergic receptors. Separately, physical exercise and central insulin
      administration exert relevant roles in cognitive function. We here use CF1 mice
      to investigate (i) the effects of voluntary exercise on hippocampal insulin
      signaling and memory performance and (ii) whether central insulin administration
      alters the effects of exercise on hippocampal insulin signaling and memory
      performance. Adult mice performed 30 days of voluntary exercise on running wheel
      and afterward both, sedentary and exercised groups, received
      intracerebroventricular (icv) injection of saline or insulin (0.5-5 mU). Memory
      performance was assessed using the inhibitory avoidance and water maze tasks.
      Hippocampal tissue was measured for [U-(14)C] glucose oxidation and the
      immunocontent of insulin receptor/signaling (IR, pTyr, pAktser473). Additionally,
      the phosphorylation of the glutamate NMDA receptor NR2B subunit and the capacity
      of glutamate uptake were measured, and immunohistochemistry was used to determine
      glial reactivity. Exercise significantly increased insulin peripheral
      sensitivity, spatial learning, and hippocampal IR/pTyrIR/pAktser473
      immunocontent. Glucose oxidation, glutamate uptake, and astrocyte number also
      increased relative to the sedentary group. In both memory tasks, 5 mU icv insulin
      produced amnesia but only in exercised animals. This amnesia was associated a
      rapid (15 min) and persistent (24 h) increase in hippocampal pNR2B immunocontent
      that paralleled the increase in glial reactivity. In conclusion, physical
      exercise thus increased hippocampal insulin signaling and improved water maze
      performance. Overstimulation of insulin signaling in exercised animals, however,
      via icv administration impaired behavioral performance. This effect was likely
      the result of aberrant phosphorylation of the NR2B subunit.

PMID- 20824732
TI  - The early and accurate objective diagnosis of RBD--why should we care?

PMID- 20824730
TI  - High affinity group III mGluRs regulate mossy fiber input to CA3 interneurons.
AB  - Stratum lacunosum-moleculare interneurons (L-Mi) in hippocampal area CA3 target
      the apical dendrite of pyramidal cells providing feedforward inhibition. Here we
      report that selective activation of group III metabotropic glutamate receptors
      (mGluRs) 4/8 with L(+)-2-amino-4-phosphnobytyric acid (L-AP4; 10 MUM) decreased
      the probability of glutamate release from the mossy fiber (MF) terminals
      synapsing onto L-Mi. Consistent with this interpretation, application of L-AP4 in
      the presence of 3 mM strontium decreased the frequency of asynchronous MF EPSCs
      in L-Mi. Furthermore, the dose response curve showed that L-AP4 at 400 MUM
      produced no further decrease in MF EPSC amplitude compared with 20 MUM L-AP4,
      indicating the lack of mGluRs 7 at these MF terminals. We also found that one
      mechanism of mGluRs 4/8-mediated inhibition of release is linked to N-type
      voltage gated calcium channels at MF terminals. Application of the group III
      mGluR antagonist MSOP (100 MUM) demonstrated that mGluRs 4/8 are neither
      tonically active nor activated by low and moderate frequencies of activity.
      However, trains of stimuli to the MF at 20 and 40 Hz delivered during the
      application of MSOP revealed a relief of inhibition of transmitter release and an
      increase in the overall probability of action potential firing in the
      postsynaptic L-Mi. Interestingly, the time to first action potential was
      significantly shorter in the presence of MSOP, indicating that mGluR 4/8
      activation delays L-Mi firing in response to MF activity. Taken together, our
      data demonstrate that the timing and probability of action potentials in L-Mi
      evoked by MF synaptic input is regulated by the activation of presynaptic high
      affinity group III mGluRs.

PMID- 20824733
TI  - Levodopa and subthalamic deep brain stimulation responses are not congruent.
AB  - There is a consensus that in Parkinson's disease, the extent of preoperative
      levodopa responsiveness predicts the efficacy of subthalamic nucleus deep brain
      stimulation (STN DBS). However, this may be the result of statistical methods and
      primary assumptions. We were able to reproduce previously published correlation
      results on our data (N = 49 patients). Yet, these same results were demonstrated
      even after random shuffling of our data. Notably, we did not observe a
      correlation between STN DBS efficacy and preoperative levodopa responsiveness
      when using their respective baselines and fractional scores of motor improvement.
      Furthermore, postoperative responses were not limited by preoperative scores,
      with tremor demonstrating the greatest discrepancy. We conclude that preoperative
      levodopa responsiveness does not predict or limit the outcome of STN DBS. These
      results imply different therapeutic mechanisms for levodopa and STN DBS and
      therefore question the validity of using substantial preoperative levodopa
      responsiveness as a selection criterion for STN DBS.

PMID- 20824734
TI  - Metric properties of the mini-mental Parkinson and SCOPA-COG scales for rating
      cognitive deterioration in Parkinson's disease.
AB  - Parkinson's disease (PD) is a chronic neurodegenerative disorder that causes
      cognitive impairment and dementia in ~30% of patients. OBJECTIVE: Compare metric
      qualities of Mini-Mental Parkinson (MMP) and scales for outcomes in Parkinson's
      disease-cognition (SCOPA-COG) with respect to their relative reliability,
      validity and ability to predict symptoms (mobility, quality of life, social
      repercussions, and mood) in PD patients. Outpatients (n=123, 78 males/45 females)
      diagnosed with PD were included in the study. A multilevel (hierarchical)
      modeling analysis was performed along with tests of reliability and validity to
      ascertain which of the two models better predicts symptoms related to PD.
      RESULTS: The MMP differed significantly between patients with Hoehn and Yahr
      (H&Y) stages 1, 2 or versus 4/5 (grouped together). The SCOPA-COG showed
      differences only between patients in H&Y stages 2 versus 4/5. Both scales were
      dependent on educational background and age. The SCOPA-COG had a higher
      coefficient of variation (0.303) than the MMP (0.184), indicating that it was the
      more discriminative of the two. CONCLUSIONS: The SCOPA-COG has some advantages
      over the MMP, the most important being a greater discriminative ability.
      Multilevel hierarchical analysis clarified the necessity of stratifying the PD
      population according to educational background, years of illness, and H&Y stage
      when using these scales.

PMID- 20824736
TI  - A U.S. survey of patients with Parkinson's disease: satisfaction with medical
      care and support groups.
AB  - Relatively little is known about patient satisfaction with Parkinson's disease
      (PD) care and the use of support groups in the United States. We surveyed members
      of the Muhammad Ali Parkinson's Disease Registry to assess satisfaction with
      medical care and to evaluate support group use. Satisfaction was measured on a 5
      point Likert scale, with high satisfaction defined as a four or five. We used
      multiple logistic regression to identify factors associated with high
      satisfaction and support group use. The response rate was 38% (726 of 1923). Most
      (57%) expressed high satisfaction with PD care. Individuals were most satisfied
      with the time their provider spent with them (61%) and PD education (56%) but
      least satisfied with prognostic information (35%) and information about non-drug
      interventions (28%). Patients seeing a PD specialist were three times more
      satisfied with their care than those seeing a general neurologist (OR = 3.00, 95%
      CI: 1.92-4.71; P < 0.0001). Support group use is common, and 61% of survey
      respondents had attended one at any point. Caucasian race (OR = 2.85, 95% CI:
      1.45-5.61), PD duration (OR = 1.05 per year, CI: 1.01-1.10), and PD specialist
      care (OR = 1.80, CI: 1.16-2.77) were associated with greater support group
      attendance. Overall, 49% reported high satisfaction with their support group. The
      greatest concerns were specific needs not being addressed (15%) and insufficient
      expertise within the group (14%). Most individuals with Parkinson's disease
      expressed high levels of satisfaction, especially with specialist care. Specialty
      care and improved education, in the clinic or through support groups, may enhance
      satisfaction and health care quality.

PMID- 20824735
TI  - The alpha2 adrenergic antagonist fipamezole improves quality of levodopa action
      in Parkinsonian primates.
AB  - Reduction in the antiparkinsonian benefit of levodopa is a major complication of
      long-term levodopa treatment in advanced Parkinson's disease (PD). Such loss of
      benefit arises because of reduced duration of action and appearance of disabling
      dyskinesia. We assess the potential of the alpha(2) adrenergic antagonist
      fipamezole to reduce motor complications in parkinsonian macaques. MPTP-lesioned
      macaques were treated acutely with fipamezole (10 mg/kg) alone and in combination
      with two doses of levodopa. Fipamezole extended both duration and quality of
      antiparkinsonian action of levodopa. Duration of antiparkinsonian action, on
      time, was increased by up to 75% while "good-quality" on time, i.e., that not
      associated with disabling dyskinesia, was increased by up to 98%. Combination of
      fipamezole with the lower dose of levodopa provided antiparkinsonian benefit at
      least equivalent to that provided by the higher dose levodopa alone. However,
      with the combination, antiparkinsonian benefit was of much better quality. The
      proportion of on time without disabling dyskinesia (79%) was significantly
      greater than that with high dose levodopa alone (45%). Increased duration and
      quality of levodopa action may represent therapeutically valuable actions of
      alpha(2) adrenergic antagonists.

PMID- 20824737
TI  - Transcatheter closure of ruptured sinus of Valsalva aneurysm.
AB  - Congenital sinus of Valsalva aneurysm is a rare cardiovascular anomaly. Rupture
      of sinus of Valsalva (RSOV) is a rare occurrence, occurring in 10-20% of cases.
      Rupture into right atrium is further a rare occurrence. The rupture is usually a
      catastrophic event presenting as acute onset congestive cardiac failure in an
      apparently healthy individual in the 2(nd) or 3(rd) decade of life. Surgery used
      to be the mainstay of treatment of RSOV aneurysm, however, in past few years
      several reports of transcatheter closure of RSOV have come into light. We report
      a patient, who underwent device closure with a Duct Occluder device. Device was
      manipulated and deployed with an angle so as to prevent aortic valve dysfunction.
      (c) 2010 Wiley-Liss, Inc.

PMID- 20824738
TI  - The effect of mouth breathing versus nasal breathing on dentofacial and
      craniofacial development in orthodontic patients.
AB  - OBJECTIVES/HYPOTHESIS: To determine the effect of mouth breathing during
      childhood on craniofacial and dentofacial development compared to nasal breathing
      in malocclusion patients treated in the orthodontic clinic. STUDY DESIGN:
      Retrospective study in a tertiary medical center. METHODS: Clinical variables and
      cephalometric parameters of 116 pediatric patients who had undergone orthodontic
      treatment were reviewed. The study group included 55 pediatric patients who
      suffered from symptoms and signs of nasal obstruction, and the control group
      included 61 patients who were normal nasal breathers. RESULTS: Mouth breathers
      demonstrated considerable backward and downward rotation of the mandible,
      increased overjet, increase in the mandible plane angle, a higher palatal plane,
      and narrowing of both upper and lower arches at the level of canines and first
      molars compared to the nasal breathers group. The prevalence of a posterior cross
      bite was significantly more frequent in the mouth breathers group (49%) than nose
      breathers (26%), (P = .006). Abnormal lip-to-tongue anterior oral seal was
      significantly more frequent in the mouth breathers group (56%) than in the nose
      breathers group (30%) (P = .05). CONCLUSIONS: Naso-respiratory obstruction with
      mouth breathing during critical growth periods in children has a higher tendency
      for clockwise rotation of the growing mandible, with a disproportionate increase
      in anterior lower vertical face height and decreased posterior facial height.

PMID- 20824739
TI  - A new thread guide instrument for endoscopic arytenoid lateropexy.
AB  - OBJECTIVES/HYPOTHESIS: The varied etiology of bilateral vocal cord immobility
      (BVCI) requires a wide range of surgical approaches. A new endolaryngeal thread
      guide instrument (ETGI) is presented here for a minimally invasive endoscopic
      lateropexy of the arytenoid cartilage, which might serve as a basis for a simple
      solution for the main types of BVCI. STUDY DESIGN: Prospective study of BVCI
      patients who underwent surgery, including 22 bilateral vocal cord paralyses
      (BVCP), 12 mechanical fixations (MF), 10 posterior glottic stenoses, and two
      rheumatoid ankyloses. METHODS: The ETGI is based on a built-in movable curved
      blade with a hole at its tip to guide a thread in and out again between the skin
      and the laryngeal cavity. The loops formed around the arytenoid cartilage cause
      abduction. In cases of fixations, the cricoarytenoid joints were properly
      mobilized as a first step with a combination of cold technique and CO(2) laser.
      RESULTS: As spirometric tests proved, 32 patients achieved improved breathing
      ability. One temporary tracheostomy was necessary and one patient with ongoing
      radiotherapy could not be decannulated. Subjectively, twelve patients' voices
      improved or approximated normal quality due to complete vocal cord recoveries on
      at least one side after lateropexy was ceased. Incomplete recovery with more or
      less impaired voice was observed in 16 cases. Three MF patients and two BVCP
      patients with poor overall health condition had severe dysphonia. CONCLUSIONS:
      Combined with simple and readily available methods, endoscopic arytenoid
      lateropexy is an effective solution for BVCIs with various etiologies. The ETGI
      facilitates this procedure with rapid and safe creation of fixating loops at the
      proper position.

PMID- 20824740
TI  - Optical coherence tomography allows for the reliable identification of laryngeal
      epithelial dysplasia and for precise biopsy: a clinicopathological study of 61
      patients undergoing microlaryngoscopy.
AB  - OBJECTIVES/HYPOTHESIS: A newly developed microscope-based spectral-domain optical
      coherence tomography (SD-OCT) device and an endoscope-based time-domain OCT (TD
      OCT) were used to assess the inter-rater reliability, sensitivity, specificity,
      and accuracy of benign and dysplastic laryngeal epithelial lesions. STUDY DESIGN:
      Prospective study. METHODS: OCT during microlaryngoscopy was done on 35 patients
      with an endoscope-based TD-OCT, and on 26 patients by an SD-OCT system integrated
      into an operating microscope. Biopsies were taken from microscopically suspicious
      lesions allowing comparative study of OCT images and histology. RESULTS:
      Thickness of the epithelium was seen to be the main criterion for degree of
      dysplasia. The inter-rater reliability for two observers was found to be kappa =
      0.74 (P <.001) for OCT. OCT provided test outcomes for differentiation between
      benign laryngeal lesions and dysplasia/CIS with sensitivity of 88%, specificity
      of 89%, PPV of 85%, NPV of 91%, and predictive accuracy of 88%. However, because
      of the limited penetration depth of the laser light primarily in hyperkeratotic
      lesions (thickness above 1.5 mm), the basal cell layer was no longer visible,
      precluding reliable assessment of such lesions. CONCLUSIONS: OCT allows for a
      fairly accurate assessment of benign and dysplastic laryngeal epithelial lesion
      and greatly facilitates the taking of precise biopsies. Laryngoscope, 2010.

PMID- 20824741
TI  - Transoral robotic resection of recurrent nasopharyngeal carcinoma.
AB  - Transoral robotic nasopharyngectomy was carried out for a patient who developed
      recurrent nasopharyngeal cancer after radiotherapy. The tumor in the left lateral
      wall of the nasopharynx was exposed after splitting the soft palate and a
      curative resection, including the medial crus of the eustachian tube was carried
      out under the three-dimensional 0 degrees  camera. The operative procedure was
      uncomplicated, blood loss was minimal and the patient recovered smoothly. The
      camera of the surgical robot provided superb visualization of the operative field
      and the maneuverability of the robotic arms with the Endowrist design allowed
      adequate tumor extirpation. The morbidity associated with the procedure was
      minimal, and this surgical procedure can be applied for resection of small and
      favorably located residual or recurrent nasopharyngeal cancer or other
      appropriate pathologies in the region. Laryngoscope, 2010.

PMID- 20824742
TI  - Ultrasound-guided needle aspiration: impact of immediate cytologic review.
AB  - OBJECTIVES/HYPOTHESIS: To compare the diagnostic adequacy of ultrasound-guided
      fine-needle aspiration biopsy (USFNA) of the head and neck with immediate on-site
      microscopic evaluation and feedback by a cytopathologist (IMMEDIATE) versus
      delayed examination without immediate feedback (DELAYED). STUDY DESIGN:
      Retrospective chart review of office-based USFNA performed in both IMMEDIATE and
      DELAYED settings by the same otolaryngologist. METHODS: A total of 199 USFNA
      procedures in the head and neck were performed by one practitioner. Of these
      procedures, 137 biopsies were performed in the DELAYED setting, whereas 62
      biopsies were performed in the IMMEDIATE setting. Cytopathology reports were
      reviewed for diagnostic conclusions as well as adequacy of biopsies. The results
      from both settings were compared using Pearson chi2 test. RESULTS: The ability to
      obtain a diagnosis from USFNA was 73.0% in the DELAYED group as compared with
      90.3% in the IMMEDIATE group. The rate of adequate cells on biopsy was 89.1% in
      the DELAYED group as compared with 96.8% in the IMMEDIATE group. There was a
      statistically significant difference between observed and expected diagnostic
      rates (chi(2)[1] = 7.568, P = .006) and a trend toward a significant difference
      between the observed and expected adequacy rates (chi(2)[1] = 3.259, P = .071)
      when IMMEDIATE evaluation by a cytopathologist was performed. CONCLUSIONS: An
      immediate microscopic evaluation of USFNA specimens to confirm adequacy of
      sampling is strongly recommended. Diagnostic conclusions were increased when an
      evaluation of the specimen was performed at the time of biopsy. The specimen
      adequacy rate tended to increase with an immediate cytopathologic assessment.
      Laryngoscope, 2010.

PMID- 20824743
TI  - Outcomes of vascularized bone graft reconstruction of the mandible in
      bisphosphonate-related osteonecrosis of the jaws.
AB  - OBJECTIVES/HYPOTHESIS: To describe the clinical entity and therapeutic challenges
      of bisphosphonate-related osteonecrosis of the jaws (BRONJ). The use of
      vascularized bone grafts for reconstruction of the mandible in extensive BRONJ is
      proposed. STUDY DESIGN: Multi-institutional retrospective review. METHODS:
      Patients undergoing mandible reconstruction with vascularized bone grafts after
      segmental mandible resection for BRONJ were evaluated. Mandible reconstruction
      was only performed on patients with intractable pain, fistulae, or pathologic
      fracture and after failure of comprehensive conservative therapy. No patients had
      a history of primary or metastatic head and neck malignancy or radiation therapy.
      Bone union was established with follow-up radiography. RESULTS: Eleven patients
      met inclusion criteria. Mean patient age was 61.3 years. Median follow-up was
      13.9 months. All patients had undergone therapy with bisphosphonates and had no
      other identifiable cause of mandible osteonecrosis. Preoperatively, pathologic
      mandible fractures were present in 73% of patients, and 36% had orocutaneous
      fistulae. Fibula osteocutaneous flaps were used in all cases with no failures. In
      all patients, bony union was demonstrated clinically and radiographically.
      Postoperative wound complications occurred in 36% of patients but were all
      treated successfully with conservative therapy. There was no BRONJ recurrence
      within the study follow-up period. CONCLUSIONS: Osteonecrosis is a significant
      complication of bisphosphonate therapy, and current literature does not support
      vascularized reconstruction. We demonstrate that vascularized bone graft
      reconstruction with the fibula free flap offers a high success rate of bony union
      and fistula closure and should be offered to selected patients with advanced
      cases of BRONJ.

PMID- 20824744
TI  - Transcatheter aortic valve implantation for treatment of patients with
      degenerated aortic bioprostheses--valve-in-valve technique.
AB  - BACKGROUND: The management of patients with degeneration of surgical
      bioprosthetic valve replacement remains a challenge because of the higher risk of
      re-do aortic valve replacement. We present a case series of five patients with
      degenerated aortic bioprostheses treated with transfemoral transcatheter aortic
      valve implantation (TAVI). METHODS: From December 2009 to May 2010, five patients
      with degenerated aortic valve bioprostheses (aortic valve area < 1 cm(2) or
      severe aortic regurgitation), an excessive operative risk (EuroSCORE >= 30%),
      symptoms of heart failure (NYHA >= III) and an internal diameter of bioprosthetic
      aortic valve 20.5 +/- 0.5 mm were included. Procedures were performed without
      hemodynamic support using femoral arteries. Balloon valvuloplasty with a 20-mm
      balloon under rapid pacing was carried out before valve implantation. The 26-mm
      CoreValve prosthesis, 18-F-generation (Medtronic, Minneapolis, Minnesota) was
      inserted retrograde under fluoroscopic guidance. Invasive and echocardiographic
      measurements were done immediately before and after TAVI. Clinical followup and
      echocardiography were performed after procedure (mean followup 72 days +/- 60,
      range: 176-30 days). RESULTS: In all patients TAVI was successful with immediate
      decrease of transaortic peak-to-peak pressure (P = 0.002). Mild aortic
      regurgitation occurred in two patients and one patient received a new permanent
      pacemaker. Major adverse cardiac and cerebrovascular events did not arise. NYHA
      functional class improved in all patients and left ventricular ejection fraction
      increased (P = 0.019). CONCLUSION: Our experiences with the valve-in-valve
      technique using the CoreValve prosthesis suggest that transfemoral TAVI is
      feasible in high risk patients with degenerated aortic bioprostheses.

PMID- 20824745
TI  - Severe coronary disease not amenable to revascularization: are the series clearly
      defined?

PMID- 20824746
TI  - Three-dimensional computed tomography in the cardiac catheterization laboratory.
AB  - OBJECTIVES: To establish the feasibility of fusion of a 3-dimensional computed
      tomography (3D CT) dataset to the routine fluoroscopic image in the cardiac
      catheterization laboratory. BACKGROUND: Routine fluoroscopic imaging in the
      cardiac catheterization laboratory often does not provide adequate anatomic
      detail for structural cardiac interventions. The modern C-arm is capable of
      acquiring CT-like 3D images (Syngo DynaCT), and the overlay of CT-acquired
      details on the fluoroscopic image may be useful. The feasibility of this new
      technology has not yet been reported. METHODS: Three patients (presenting with
      three different clinical indications) were selected, all of whom had previously
      undergone contrast-enhanced chest CT. Anatomic details of interest were marked on
      the preprocedural CT, and the CT was registered to a DynaCT acquired in the
      catheterization laboratory. The CT:CT registration was then fused to the "real
      time" fluoroscopic image. RESULTS: Fusion of the CT to the fluoroscopic image was
      successful in these three patients and provided a substantial degree of anatomic
      guidance for catheter and device manipulation. CONCLUSIONS: We have demonstrated
      the ability to delineate cardiovascular structures of interest on the "real-time"
      fluoroscopic image using CT fusion. Future studies should address whether this
      technology can reduce overall contrast administration and radiation dose.

PMID- 20824747
TI  - PCI using a 4-Fr "child" guide catheter in a "mother" guide catheter: Kyushu
      KIWAMI(r) ST registry.
AB  - OBJECTIVES: With the development of PCI techniques, the indications for stents
      have been expanding as well. On the other hand, we often encounter the situations
      where deploying a stent/stents by the conventional method is technically
      challenging. We report a novel stent delivery system using a newly developed 4Fr.
      straight catheter with Mother-and-Child method. METHODS AND RESULTS: We collected
      the data on coronary angioplasty in which we experienced the difficulty to
      deliver coronary stents and used 4Fr. KIWAMI ST01. The case number amounts to 32
      cases over a six-month period from October 2009 through March 2010. The
      angioplasty was performed for lesions in the RCA in 9 patients (28%), lesions in
      the LAD in 15 patients (47%), lesions in the LCX in 5 patients (16%), lesions in
      the saphenous vein grafts in 2 patients (6%), and lesions in the internal
      thoracic artery (LITA) grafts in 1 patient (3%). And the reasons for the
      difficult stent delivery by the conventional methods were as follows: severe
      calcification in 12 patients (37%), intense tortuosity in 7 patients (22%), poor
      backup support for guide catheter in 8 patients (25%), and trapping of the stent
      proximal to the target lesion in 5 patients (16%). The dislodgment of stent did
      not happened in all cases. CONCLUSIONS: KIWAMI(r) ST01 stent delivery system is
      feasible, safer, and effective in cases where stent delivery is difficult by the
      conventional method.

PMID- 20824748
TI  - Sheathless transradial intervention using standard guide catheters.
AB  - OBJECTIVES: Our aim was to report our preliminary experience performing complex
      transradial interventions using a sheathless technique with standard large bore
      nonhydrophilic guiding catheters. BACKGROUND: A major limitation of transradial
      percutaneous coronary intervention (PCI) is the inability to use large guides
      because of the relatively small size of the radial artery. METHODS: We identified
      consecutive patients who had transradial PCI between September 2009 and March
      2010 using large-bore guides (7 or 8 Fr) with a sheathless technique. RESULTS:
      Ten patients were identified (90% men, mean age 68.8 +/- 9.8 years). Indications
      for PCI were stable angina (60%) and acute coronary syndrome (40%). Treatment was
      attempted on 15 vessels. Bifurcation lesions were present in six patients. One
      patient had a chronic total occlusion, one had a saphenous vein bypass graft
      lesion requiring filter wire placement prior to intervention, and one patient
      required rotational atherectomy. In the majority of patients (60%) a 7-Fr guiding
      catheter was used for the intervention; 8-Fr guide catheters were used four
      patients. PCI was unsuccessful in one vessel; this was a completely occluded
      obtuse marginal which could not be crossed. There were no radial artery access
      site complications and in no case was cross-over to a femoral artery access site
      required. One minor coronary complication occurred. CONCLUSIONS: Sheathless
      transradial PCI using standard large-bore guiding catheters is a safe and
      effective method for treatment of complex lesions.

PMID- 20824749
TI  - Subintimal angioplasty with a true reentry device for treatment of chronic total
      occlusion of the arteries of the lower extremity.
AB  - OBJECTIVE: To report the efficacy and safety of the Outback((r)) LTD((r)) Re
      Entry Catheter in reentering the distal true lumen during percutaneous
      intentional extraluminal revascularization (PIER). BACKGROUND: Reentry catheters
      are used to treat chronic, total arterial occlusions of the lower extremities
      when standard methods of recanalization have failed. Success and complication
      rates of these catheters in the real world are uncertain and variable. METHODS: A
      retrospective review of our peripheral catheterization database from January 2004
      to September 2009 was undertaken to identify consecutive cases of peripheral
      chronic total occlusions (CTOs) requiring the use of the Outback reentry
      catheter. Patient demographics, indication for the procedure, location and extent
      of occlusion, procedural success, and complications were studied. RESULTS: A
      total of 51 patients were identified. Of the 51, 28 (54.9%) patients presented
      with nonhealing ulcer and 22 (43.1%) had lifestyle-limiting claudication. One
      patient presented with acute limb ischemia. There were 6 (11.8%) patients with
      common iliac artery occlusion, 2 (3.9%) with external iliac artery occlusion, 1
      (1.9%) with common femoral artery occlusion, 35 (68.6%) with superficial femoral
      artery occlusion, 6 (11.8%) with popliteal artery occlusion, and 1 (1.9%) with
      tibioperoneal artery occlusion. Median lesion length was 230 mm. Procedural
      success was achieved in 49 patients (96.1%). There was 1 (1.9%) periprocedural
      complication. CONCLUSION: Use of Outback((r)) LTD((r)) Re-Entry Catheter is a
      safe and valuable option for PIER/subintimal angioplasty and recanalization in
      patients with symptomatic lower-extremity CTOs. However, long-term patency
      remains unknown.

PMID- 20824750
TI  - Frequency and risk of noncardiac surgery after drug-eluting stent implantation.
AB  - BACKGROUND: Few studies have described the frequency and risk of surgery after
      drug-eluting stent (DES) implantation. METHODS: The medical records of 827
      consecutive patients who received a DES at our institution between January 1,
      2005 and July 1, 2008 were retrospectively reviewed to determine the outcomes of
      patients who subsequently underwent noncardiac surgery. RESULTS: During a median
      follow-up of 21 months, 135 patients underwent 191 noncardiac surgeries. The
      incidence of noncardiac surgery was 7% at 1 year, 18% at 2 years, and 22% at 3
      years. Mean age was 62 years and 96% were men. A perioperative complication
      occurred in 19 surgeries (10%): excessive bleeding in 11 patients (6%),
      myocardial infarction in four patients (2%), acute renal failure in one patient
      (0.5%), hypotension and syncope in one patient (0.5%) and postoperative death in
      three patients (1.6%). Stent thrombosis occurred in one patient (0.5%). A
      complication occurred in six of 58 surgeries (10%) in which patients received
      perioperative clopidogrel vs. 13 of 133 surgeries (10%) in which patients did not
      receive perioperative clopidogrel (P = 0.90). Complications occurred in three of
      25 surgeries performed within 6 months (16%), in four of 37 surgeries performed
      between 6 and 12 months (11%), and in 12 of 129 surgeries performed after >12
      months (9%) from DES implantation (P = 0.90). CONCLUSION: Noncardiac surgery is
      frequently needed in the years after DES implantation and appears to carry a low
      risk of stent thrombosis and perioperative complications.

PMID- 20824751
TI  - Valvuloplasty for tricuspid stenosis caused by a ventriculoatrial shunt.
AB  - A 45-year-old lady developed significant symptomatic tricuspid valve stenosis due
      to a ventriculoatrial (VA) shunt, implanted in childhood for idiopathic
      hydrocephalus. This appeared to be a rare complication of a VA shunt. After
      detailed discussions in multidisciplinary meeting, she underwent successful
      treatment with a single balloon valvuloplasty. To date, she has not suffered any
      complications.

PMID- 20824752
TI  - Quality of life and health status after percutaneous coronary intervention in
      stable angina patients: results from the real-world practice.
AB  - BACKGROUND: Percutaneous coronary interventions (PCI) are associated with quality
      of life (QoL) and health status improvements in stable angina patients. There are
      few studies assessing the magnitude of this effect and its predictors in
      contemporary daily practice. METHODS: Prospective cohort study with stable angina
      patients submitted to PCI in a tertiary interventional cardiology center. The
      clinical characteristics and the Seattle Angina Questionnaire (SAQ) were assessed
      before PCI, and patients were followed-up for 1 year. Mixed linear regression and
      ANOVA were used to compare SAQ indices, and multivariate analysis to identify
      predictors of QoL improvement. RESULTS: Between September 2006 and May 2007, 110
      patients were included. The mean age of the study population was 62.8 +/- 8.7
      years, and 62% of the patients were of the male gender. Diabetes mellitus was
      present in 29%, arterial hypertension in 82%, previous myocardial infarction in
      32%, and previous PCI in 29%. Before PCI, only 5% of the patients were free of
      angina, and this rate improved to 68% in the one-year followup (P < 0.001). There
      was improvement in all SAQ scales in the one-year followup, which was already
      shown in the 6-month assessment (P < 0.0001). Quality of life before the
      procedure was the main predictor of QoL improvement by multivariate analysis (P <
      0.001). CONCLUSIONS: Patients with stable angina submitted to PCI in the real
      world practice present significant improvement in one-year health status, as
      assessed by the SAQ. Quality of life before the procedure is the main determinant
      of improvement in QoL.

PMID- 20824753
TI  - Echo-guided presentation of the aortic valve minimises contrast exposure in
      transcatheter valve recipients.
AB  - OBJECTIVES: We have developed a method using transthoracic echocardiography in
      establishing optimal visualization of the aortic root, to reduce the amount of
      contrast medium used in each patient. BACKGROUND: During transcatheter aortic
      valve implantation, it is necessary to obtain an optimal fluoroscopic projection
      for deployment of the valve showing the aortic ostium with the three cusps
      aligned in the beam direction. This may require repeat aortic root angiograms at
      this stage of the procedure with a high amount of contrast medium with a risk of
      detrimental influence on renal function. METHODS: We studied the conventional way
      and an echo guided way to optimize visualisation of the aortic root.
      Echocardiography was used initially allowing easier alignment of the image
      intensifier with the transducer's direction. RESULTS: Contrast volumes,
      radiation/fluoroscopy exposure times, and postoperative creatinine levels were
      significantly less in patients having the echo-guided orientation of the optimal
      fluoroscopic angles compared with patients treated with the conventional
      approach. CONCLUSION: We present a user-friendly echo-guided method to facilitate
      fluoroscopy adjustment during transcatheter aortic valve implantation. In our
      series, the amounts of contrast medium and radiation have been significantly
      reduced, with a concomitant reduction in detrimental effects on renal function in
      the early postoperative phase.

PMID- 20824754
TI  - Long-term risk of clinical events from stenting side branches of coronary
      bifurcation lesions with drug-eluting and bare-metal stents: an observational
      meta-analysis.
AB  - OBJECTIVES: To compare the long-term risks of coronary bifurcation lesions
      treated with side-branch stenting using drug-eluting versus bare-metal stents.
      BACKGROUND: Side-branch stenting is an off-label practice, but when needed, the
      incidence of late adverse events may differ between drug-eluting and bare-metal
      stents. METHODS: We systematically searched PubMed, and the National Institutes
      of Health and Cochrane Registries for studies of coronary bifurcation stenting
      reporting clinical outcomes over at least 5 months. Data were extracted and cross
      checked independently by two investigators for inclusion in an observational meta
      analysis. Clinical outcomes included major adverse clinical events (MACE), death,
      myocardial infarction, target vessel revascularization (TVR), and definite stent
      thrombosis. We used random-effects models and meta-regression in 6,825 subjects
      from 42 studies. RESULTS: Most (79%) of the heterogeneity in MACE between
      treatment groups was explained by differences in stent type, side-branch
      stenting, and length of follow-up. Compared with drug-eluting stents without side
      branch stenting, drug-eluting stents with side-branch stenting had a 3% higher
      incidence of myocardial infarction [95% confidence interval (CI) = 0.3%, 5%, P <
      0.05], but no significant increase in MACE, death, TVR, or stent thrombosis. Bare
      metal stenting without side-branch stenting had 10% (95% CI = 3%, 16%, P < 0.01)
      higher MACE, and 10% (95% CI = 4%, 17%, P < 0.01) higher TVR, whereas bare-metal
      side-branch stenting had 31% (95% CI = 23%, 39%, P < 0.001) higher MACE, and 19%
      (95% CI = 10%, 28%, P < 0.001) higher TVR. CONCLUSIONS: Side-branch stenting has
      a much smaller impact on long-term MACE with drug-eluting stents compared with
      bare-metal stents. Although this study does not support routine side-branch
      stenting, when side-branch stenting is required, drug-eluting stents are
      associated with less adverse outcomes.

PMID- 20824755
TI  - Transapical aortic balloon valvuloplasty in a 890-gram infant: hybrid is better!
AB  - Balloon aortic valvuloplasty has become in many centers the treatment of choice
      for neonates with critical or severe aortic stenosis. Usual approaches both
      antegrade and retrograde can be problematic in preterms extremely low birth
      weight babies. We describe a novel approach for dilating the aortic valve in an
      890 grams baby.

PMID- 20824756
TI  - Aortic coarctation complicated by wall aneurysm: the role of covered stents.
AB  - OBJECTIVES: To evaluate the management of aneurysms associated with aortic
      coarctation by covered stent deployment. BACKGROUND: Aortic aneurysm formation
      complicating aortic coarctation carries a risk of rupture with high mortality
      rate. Surgical repair has a significant mortality and may be associated with
      central nervous system injury, including paraplegia. Transcatheter intervention
      alternatively carries a risk of aneurysmal rupture. METHODS: Between July 2004
      and September 2009, 140 consecutive patients underwent percutaneous stent
      implantation to treat aortic coarctation. Eleven (7.9%) patients had coarctation
      associated with aortic wall aneurysm: three with native coarctation with wall
      aneurysm, three with previous surgical coarctation repair, three with previous
      balloon angioplasty, and two with previous bare stent implantation. The e-PTFE
      covered 8Zig Cheatham-Platinum stents were used to treat all 11 patients.
      RESULTS: Median age at procedure was 13 years (range, 6-66 years). Successful
      device deployment was achieved in all patients. Systolic pressure gradient
      reduced significantly from a median baseline of 30 mm Hg (range, 25-50 mm Hg) to
      a postprocedural median of 5 mm Hg (range, 0-20 mm Hg) (P < 0.01). Aortic
      diameter increased from a median value of 6 mm (range, 0.5-11 mm) to a median
      value of 12 mm (range, 10-22 mm) (P < 0.001). No early complications occurred,
      with successful relief of stenoses and complete sealing of all aneurysms. Median
      follow-up was 50 months (range, 16-61 months). Redilatation was required in four
      patients (one patient with intrastent restenosis secondary to significant
      endothelial growth, whereas the other three patients showed restenosis secondary
      to somatic growth). Redilatation with a larger balloon was performed without
      complication in all cases. CONCLUSIONS: Our data show that covered stents are a
      safe and effective treatment with low risk of complications for the treatment of
      coarctation associated with aortic wall aneurysm.

PMID- 20824757
TI  - Wingspan stenting with modified predilation for symptomatic middle cerebral
      artery stenosis.
AB  - OBJECTIVES: Our purpose was to assess the feasibility, safety, and effectiveness
      of a modified predilation for middle cerebral artery (MCA) stenosis. BACKGROUND:
      Wingspan stenting of MCA remains a technical challenge, and rates of residual
      stenosis and restenosis must be lowered. METHODS: A series of 48 patients with
      symptomatic MCA stenosis greater than 50% and refractory to medical therapy
      underwent Wingspan stenting with different balloon/artery ratios before (group 1,
      Boston guidelines predilation) or after (group 2, modified predilation) July of
      2008. Technical success, periprocedural complications, recurrent symptoms, and
      restenosis were assessed retrospectively, and risk factors for restenosis were
      analyzed using logistic regression. RESULTS: Successful stenting occurred in 48
      of 49 (98%) lesions. Primary endpoints within 30 days included one (2.12%) minor
      stroke and two (4.26%) transient ischemic attacks. Stenoses were reduced from
      77.11% +/- 10.09% to 27.50% +/- 6.91% in group 1 versus from 72.56% +/- 10.46% to
      8.20% +/- 5.41% in group 2. A total of 43 patients were followed up for 12.92 +/-
      5.08 months, and recurrent stroke or transient ischemic attack occurred in two
      (4.65%) patients. Vessels were followed with transcranial Doppler (43 vessels),
      angiography (23 vessels), or computed tomographic angiography (one vessel). The
      restenosis rate was 8 of 18 (44%) in group 1 and 3 of 25 (12%) in group 2.
      Restenosis was associated with residual stenosis and diabetes. CONCLUSIONS:
      Wingspan stenting for symptomatic MCA stenosis can be performed with high success
      and low complication rates, and modified predilation with the Gateway balloon can
      reduce the rates of residual stenosis and restenosis.

PMID- 20824758
TI  - Five-year clinical outcomes of sirolimus-eluting versus paclitaxel-eluting stents
      in high-risk patients.
AB  - OBJECTIVES AND BACKGROUND: First generation drug-eluting stents have shown
      differential efficacy in high-risk patient subsets at one year. It is unclear
      whether these differences endure over the medium- to long-term. We compared the
      five-year clinical efficacy and safety of sirolimus-eluting stents (SES) and
      paclitaxel-eluting stents (PES) in a population of high-risk patients. METHODS:
      The patient cohorts of the ISAR-DESIRE, ISAR-DIABETES, and ISAR-SMART-3
      randomized trials were followed up for five years and data were pooled. The
      primary efficacy endpoint of the analysis was the need for target lesion
      revascularization (TLR) during a five-year follow-up period. The primary safety
      endpoint was the combination of death or myocardial infarction (MI) after five
      years. RESULTS: A total of 810 patients (405 patients in the SES group and 405
      patients in the PES group) was included. Over five years TLR was reduced by 39%
      with SES compared with PES stent (hazard ratio [HR] 0.61; 95% confidence interval
      [CI] 0.44-0.85; P = 0.004). No difference was observed according to death or MI
      rates between the two groups (HR 1.10; 95% CI 0.80-1.50; P = 0.57). Definite
      stent thrombosis occurred in 0.2% (n = 1) in the SES group and in 1.6% (n = 6) in
      the PES group (HR 0.16; 95% CI 0.02-1.34; P = 0.12). CONCLUSIONS: In high-risk
      patient subsets the lower rate of 12-month TLR observed with SES in comparison
      PES is maintained out to five years. In terms of safety, although there was no
      difference in the overall incidence of death or MI, there was a trend towards
      more frequent stent thromboses with PES.

PMID- 20824759
TI  - Intracoronary delivery of eptifibatide with the ClearWay(r) RX infusion catheter.
AB  - Acute coronary syndromes are caused by plaque rupture and the formation of an
      occlusive thrombus. Intracoronary (IC) bolus administration of eptifibatide may
      result in higher levels of platelet glycoprotein IIb/IIIa (GP IIb/IIIa) receptor
      occupancy (RO) in the local coronary bed, disaggregate thrombus in the epicardial
      artery, and microvasculature and thereby improve coronary flow. We report the use
      of the ClearWay(r) catheter to deliver IC eptifibatide to the lesion,
      theoretically thereby achieving higher local coronary concentrations of the
      eptifibatide, achieving a longer residence time and maximizing drug
      bioavailability at the site of the thrombus over the standard intravenous
      delivery mechanism and over intracoronary bolus administration via the guide
      catheter. This may then lead to superior thrombus disaggregation and improved
      microvascular perfusion. (c) 2011 Wiley-Liss, Inc.

PMID- 20824760
TI  - Percutaneous transluminal renal stenting for transplant renal artery stenosis.
AB  - OBJECTIVES: Renal transplantation is a well-accepted therapeutic option for
      patients with end stage renal disease. Renal artery stenosis occurring in a
      transplanted kidney is a potentially serious condition and adversely affects
      graft survival and prognosis. The objective of this study is to document the
      immediate and intermediate term clinical results of renal stenting in this rare
      subset of renal artery stenosis. BACKGROUND: There is limited data about the
      effectiveness of renal stenting in transplant renal artery stenosis. METHODS:
      Eight patients, aged between 22 and 51 (42.5 +/- 9.25) years, were referred to
      our tertiary care interventional cardiology services for renal intervention. The
      diagnosis of transplant renal artery stenosis was based on clinical presentation
      (uncontrolled hypertension (n = 4, 50%), worsening renal function (n = 3, 37.5%)
      or flash pulmonary oedema (n = 1, 12.5%)] and Doppler ultrasound. RESULTS: All
      patients had live donor renal transplant using end to end anastomosis 2 to 11
      (6.25 +/- 3.24) months prior to intervention. Angiography revealed discrete
      stenosis at the anastomotic site. Intrarenal stenting performed from femoral
      access using 6 F accessories produced excellent angiographic results. There were
      no access site or procedure related complications. The intervention produced
      excellent immediate and intermediate term clinical results. In three patients,
      there was stabilization of renal function during 62 +/- 9.16 months of follow-up
      with decrease in serum creatinine by 38.86 +/- 6.62 %; P = 0.0476. In four
      patients with refractory hypertension, excellent blood pressure control was
      achieved with a reduction in mean blood pressure by 25.95 +/- 5.48 mm Hg (from
      122.4 +/- 5.7 to 96.45 +/- 2.45 mm Hg; P = 0.0002) during 65.25 +/- 23.79 months
      follow-up. There was decrease in antihypertensive drug requirement from 3.75 +/-
      0.5 to 1.75 +/- 0.5. During follow-up, Doppler ultrasound documented a high peak
      systolic velocity in one asymptomatic patient with well controlled blood pressure
      and preserved renal function. Sustained benefits of percutaneous
      revascularization were supported by normal Doppler parameters in the remaining
      patients. CONCLUSIONS: Percutaneous renal stenting provides excellent
      angiographic and clinical results sustained at intermediate term follow-up in
      patients with symptomatic transplant renal artery stenosis.

PMID- 20824761
TI  - Complications related to access site after percutaneous coronary interventions:
      are the adverse events underreported?
AB  - OBJECTIVES: The primary objective was to compare the NCDR rate of four access
      site related complications (arteriovenous fistula, pseudoaneurysm,
      retroperitoneal bleed, and blood transfusion) with that obtained independently
      within a Quality Improvement (QI) Database. The secondary objective was to
      determine the in-hospital mortality related to these complications. BACKGROUND:
      NCDR is the most comprehensive database of post-PCI patients and a method by
      which hospitals are compared for quality of care and outcomes. The collected data
      include in-hospital events only, therefore reporting for same day and/or early
      discharges may fail to capture adverse events. We hypothesized that the actual
      rate of complications post-PCI may be higher than the rate reported in NCDR.
      METHODS: Adverse events following PCIs were collected in a QI database. We
      compared the rate of four above mentioned complications between NCDR and our QI
      database for the time period between January 1, 2005 and December 31, 2008.
      RESULTS: A total of 3,940 PCIs were performed on 3,430 patients in the four-year
      interval. The incidence of the combined endpoint of the four adverse events was
      4.1% (161 events) in NCDR, vs. 4.7% (186 events) in QI database, a 13% higher
      yield. There was significantly higher in-hospital mortality in the complication
      group with regards to both all cause (4.7% vs. 1.1%, P < 0.0001) and
      cardiovascular mortality (2.7% vs. 1%, P = 0.046). CONCLUSIONS: Access site
      related complications occurred 13% more than what was reported in NCDR and were
      associated with a greater than fourfold increase in in-hospital mortality.

PMID- 20824762
TI  - Assessment of the aortic annulus by multislice computed tomography, contrast
      aortography, and trans-thoracic echocardiography in patients referred for
      transcatheter aortic valve implantation.
AB  - OBJECTIVE: We sought to determine the level of agreement and the reproducibility
      of trans-thoracic echocardiography (TTE), contrast aortography (CA) and
      multislice computed tomography (MSCT) for the assessment of the aortic annulus,
      in patients referred for Transcatheter Aortic Valve Implantation (TAVI).
      BACKGROUND: Correct measurement of the aortic annulus is important for TAVI.
      METHODS: The dimensions of the aortic annulus were measured using TTE, CA and
      MSCT in 70 patients with severe aortic stenosis, referred for TAVI. Agreement
      between imaging techniques and interobserver variability was assessed using the
      Bland - Altman method and a linear regression model. RESULTS: The MSCT Coronal
      view provided the largest mean annulus diameter (26.3 mm) followed by CA (24.4
      mm), MSCT Mean (23.7 mm), TTE (22.6 mm), and MSCT Sagittal (21.8 mm) view.
      Differences in the annulus measurements were significant: MSCT Coronal view
      versus CA (mean, 95% confidence interval, Pearson's correlation) 2.0 mm, -1.9 to
      6.0 mm, r = 0.72, CA versus MSCT Mean 0.2 mm, -3.3 to 3.7 mm, r = 0.76, MSCT Mean
      versus TTE 1.3 mm, -2.9 to 5.5 mm, r = 0.61, TTE versus MSCT Sagittal view 0.9
      mm, -3.6 to 5.4 mm, r = 0.59, CA versus TTE 1.5 mm, -3.0 to 5.9 mm, r = 0.57.
      Interobserver variability was: TTE (mean, 95% confidence interval, Pearson's
      correlation) 0.29 mm, -4.2 to 4.8 mm, r = 0.57, CA 0.14 mm, -3.5 to 3.8 mm, r =
      0.77, MSCT Mean 0.20 mm, -1.4 to 1.8 mm, r = 0.95. CONCLUSIONS: We found
      significant differences in the dimensions of the aortic annulus measured by MSCT,
      CA, and TTE. Interobserver variability for TTE and CA was substantially higher
      compared with MSCT.

PMID- 20824763
TI  - Feasibility of the 3D RCA catheter to engage the brachiocephalic vessels during
      carotid angiography and stenting.
AB  - BACKGROUND: Engagement of the brachiocephalic vessels during carotid angiography
      is performed using a JR-4, Vitek, or other catheters with variable success. These
      catheters require additional training for safe manipulation. In this study, we
      evaluated the feasibility of using the 3D RCA catheter which requires less
      manipulation in the aorta, and less training, to engage the brachiocephalic
      vessels. METHODS: We prospectively studied consecutive high-risk patients
      undergoing carotid angiography and stenting from August 2005 to March 2009 at our
      institution. A baseline aortogram was performed to define the arch type in all
      patients. Engagement of the brachiocephalic vessels was initially attempted using
      the 3D RCA catheter using the following approach: The 3D RCA catheter is
      positioned in the ascending aorta beyond the brachiocephalic vessels take off.
      The natural curve of the catheter usually makes it point cephalad spontaneously
      in most patients and as it is gently withdrawn it engages the aortic arch vessels
      without much manipulation. Clinical follow-up with a neurological exam was
      performed at one month and six months. RESULTS: A total of 52 patients were
      enrolled in this study. Baseline demographics and aortic arch types encountered
      are listed in Table I. The 3D RCA catheter readily engaged the brachiocephalic
      vessels in 50/52 patients (96.0 %) in our cohort of patients undergoing carotid
      angiography. Of the 52 patients, 43 subsequently underwent carotid stenting and
      shuttle sheath placement was facilitated by initial engagement of the relevant
      common carotid artery with the 3D RCA catheter. There was one transient
      neurologic complication that resolved by 5 days in a patient that underwent
      carotid stenting. CONCLUSIONS: The 3D RCA catheter can be used with a high
      success rate to engage the brachiocephalic vessels in all 3 arch types, including
      a bovine arch during carotid angiography and facilitates shuttle sheath placement
      for carotid stenting. It requires less manipulation and therefore may be a more
      operator friendly approach. (c) 2010 Wiley-Liss, Inc.

PMID- 20824764
TI  - Intercatheter reproducibility of near-infrared spectroscopy for the in vivo
      detection of coronary lipid core plaques.
AB  - OBJECTIVES: To evaluate the intercatheter reproducibility of catheter-based
      intracoronary near-infrared spectroscopy (NIRS) for the detection of coronary
      lipid core plaques (LCPs). BACKGROUND: The intercatheter in vivo reproducibility
      of coronary NIRS findings has not been evaluated. METHODS: NIRS assessment using
      an automated pullback catheter was performed in triplicates in 10 patients using
      two different NIRS catheters to evaluate the reproducibility of the lipid core
      burden index (LCBI). RESULTS: Mean age was 62 +/- 7 years, and all patients were
      men with high prevalence of hypertension (90%), hyperlipidemia (90%), diabetes
      (50%), and current smoking (50%). The mean LCBI measured by the first and second
      catheters was 64 +/- 55 and 69 +/- 47, respectively (intraclass correlation
      coefficient, 0.97; 95% confidence interval, 0.90-0.99; and Spearman's rho, 0.95;
      P < 0.001 for both). The mean LCBI measured again with the second catheter was 71
      +/- 63 (intraclass correlation coefficient, 0.96; 95% confidence interval, 0.84
      0.99; and Spearman's rho, 0.95; P < 0.001 for both). The mean number of LCPs
      detected by the first and second catheters was 1.9 +/- 1.2 and 2.0 +/- 1.5,
      respectively (intraclass correlation coefficient, 0.75, P = 0.005 and Spearman's
      rho, 0.74, P = 0.01). The mean number of LCPs at reimaging with the second
      catheter was 2.0 +/- 1.76 (intraclass correlation coefficient, 0.96 and
      Spearman's rho, 0.98; P < 0.001 for both). CONCLUSION: NIRS measurements of LCP
      with two different catheters have high reproducibility. The findings support the
      use of NIRS to assess the status of LCP in patients over time and to assess LCP
      changes in response to novel treatments.

PMID- 20824765
TI  - Left atrial appendage closure with Amplatzer cardiac plug in atrial fibrillation:
      initial European experience.
AB  - BACKGROUND: In most patients with atrial fibrillation (AF) and stroke, there is
      thrombotic embolization from the left atrial appendage (LAA). Percutaneous
      closure of the LAA is a novel alternative for the treatment of patients with AF
      at a high risk of stroke, in whom long-term anticoagulation therapy is not
      possible or not desired. This study details the initial experience with the
      Amplatzer Cardiac Plug (ACP) in humans. METHODS: Investigator-initiated
      retrospective preregistry data collection to evaluate procedural feasibility and
      safety up to 24 hr after implantation of the ACP, a nitinol device designed for
      percutaneous trans-septal implantation in LAA of patients with paroxysmal,
      permanent, or persistent AF. RESULTS: In 137 of 143 patients, LAA occlusion was
      attempted, and successfully performed in 132 (96%). There were serious
      complications in 10 (7.0%) patients (three patients with ischemic stroke; two
      patients experienced device embolization, both percutaneously recaptured; and
      five patients with clinically significant pericardial effusions). Minor
      complications were insignificant pericardial effusions in four, transient
      myocardial ischemia in two, and loss of the implant in the venous system in one
      patient. CONCLUSION: The implantation of the ACP device is a feasible method for
      percutaneous occlusion of the LAA.

PMID- 20824766
TI  - The PREHAMI (PREsillionTM in high-risk acute myocardial infarction) registry: in
      hospital and long-term outcomes.
AB  - OBJECTIVES: To evaluate the efficacy of the new Cobalt-Chromium (Co-Cr)
      PresillionTM stent for the treatment of high-risk acute myocardial infarction
      (MI) patients. BACKGROUND: Percutaneous coronary intervention (PCI) with stent
      represents the gold standard treatment for acute MI. METHODS AND RESULTS: We
      enrolled patients with high-risk acute MI (either ST-segment elevation MI or non
      ST-segment elevation MI) treated with PCI using a new Co-Cr bare metal stent with
      closed cells design and limited balloon compliance. We considered high-risk
      features as one of the following: age >= 70 years, ejection fraction <= 35%,
      glomerular filtration rate <= 60 mL/min, diabetes mellitus, rescue PCI, or
      chronic atrial fibrillation or other conditions requiring long-term oral
      anticoagulation therapy. Primary outcome of the study was rate of major adverse
      cardiac events (MACE) defined as all-cause death, new MI, and target-vessel
      revascularization. A total of 129 consecutive patients were enrolled (69 +/- 11
      years, 74% men): 71 (55%) patients with ST-segment elevation MI and 58 (45%)
      patients with non-ST-segment elevation MI. A total of 153 vessels (169 lesions
      and 179 stents) were treated. The device success rate was high (98.8%). In
      hospital MACE rate was 5.4% mainly because of death associated with the acute MI.
      At 1-year follow-up, the MACE rate was 17.3%, with 11% all-cause death (7.9% of
      cardiac origin), 0.6% of stent thrombosis, and 4.6% target-vessel
      revascularization. CONCLUSIONS: The use of the Co-Cr Presillion stent in patients
      with high-risk acute MI treated invasively seems to be safe and efficacious with
      optimal deliverability and good long-term outcomes and represents a good option
      in the treatment of these patients.

PMID- 20824767
TI  - Six-month clinical follow-up of the Tryton side branch stent for the treatment of
      bifurcation lesions: a two center registry analysis.
AB  - BACKGROUND: Treatment of bifurcation lesions with the Tryton Sidebranch stent has
      been shown to be feasible with an acceptable clinical outcome and low side branch
      late loss in the first in man trial. OBJECTIVE: To report acute procedural and
      six month clinical follow-up after the use of the Tryton Sidebranch stent in an
      "all comer" registry. METHODS: The first 100 coronary bifurcation lesions
      assigned for treatment with the Tryton stent were included in a prospective
      registry. Procedural and angiographic success rates were determined from patient
      charts and pre- and postprocedural quantitative coronary angiography. RESULTS:
      Totally, 96 patients with 100 lesions were included in the study. Seventy-two
      percent presented with stable angina, 25% with unstable angina/NSTEMI, and 3%
      STEMI. The bifurcation was located in the left main in 8%. Two lesions were
      chronic total occlusions. Sixty-nine percent were true bifurcation lesions. One
      failure of stent delivery occurred. Acute gain in SB was 0.76 +/- 0.64 mm and
      three patients had residual stenosis of >30%. Angiographic success rate was 95%;
      procedural success rate reached 94%. Peri-procedural MI occurred in two and there
      was one cardiac death during hospitalization. At a median six months follow-up,
      TLR rate was 4%, MI 3%, and cardiac death 1%. The percentage MACE-free survival
      at six months was 94%. No cases of definite stent thrombosis occurred.
      CONCLUSIONS: In a real world the use of the Tryton Sidebranch stent is associated
      with good procedural safety and angiographic success rate and acceptable outcome
      at six months of follow-up.

PMID- 20824768
TI  - A new technique for shortening a guiding catheter during retrograde
      recanalization of a chronic total occlusion.
AB  - This report introduces successful retrograde angioplasty of chronic total
      occlusion with a long collateral channel using a new technique of shortening the
      guiding catheter. With this method, we secured the lengths of the guidewire and
      the microcatheter for retrograde intervention without sacrificing the position of
      the tracked guidewire.

PMID- 20824769
TI  - Efficacy and safety of a double-coated paclitaxel-eluting coronary stent: the
      EUCATAX trial.
AB  - OBJECTIVES: The aim of this study was the comparison of a new double-coated
      paclitaxel-eluting coronary stent with bare-metal stent (BMS) in patients
      undergoing percutaneous coronary intervention. BACKGROUND: Stent coating with
      biodegradable polymers as a platform for elution of drugs has the potential for
      complete elution of drugs and for decreasing the risk of late complications.
      METHODS: Multicenter randomized trial comparing a paclitaxel-eluting stent (PES)
      coated with a biodegradable polymer and glycocalyx with the equivalent BMS. We
      randomly assigned 422 patients with de novo coronary lesions to PES (211
      patients) or to BMS (211 patients). Primary end point was target vessel failure
      (TVF) defined as cardiac death, myocardial infarction, and target vessel
      revascularization. Clinical secondary end points were target vessel
      revascularization, target lesion revascularization, stent thrombosis (ST), and
      major adverse cardiovascular events (MACE). Angiographic secondary end points
      were late loss and binary restenosis. RESULTS: At 1 year of follow-up, TVF rate
      was 9.5% in the PES group and 17.1% in the BMS group (P=0.02), and MACE rate was
      10% in PES and 19% in BMS arm (P=0.009). All other secondary end points were
      reached but ST. ST rate was low and similar in both study arms. CONCLUSIONS: The
      study shows that patients treated with PES with dual coating technology had
      significantly lower incidence of TVF and MACE than those treated with BMS design;
      however, longer follow-up should be necessary to assess true advantages of this
      technology compared with the previous one.

PMID- 20824770
TI  - Four-year clinical follow-up of the XIENCE V everolimus-eluting coronary stent
      system in the treatment of patients with de novo coronary artery lesions: the
      SPIRIT II trial.
AB  - This report describes the 4-year clinical outcomes of the SPIRIT II study, which
      randomized 300 patients to treatment with the XIENCE V everolimus-eluting stent
      (EES), or the TAXUS paclitaxel-eluting stent. At 4-year clinical follow-up, which
      was available in 256 (85.3%) patients, treatment with EES lead to a trend for
      lower rates of ischemia-driven major adverse cardiovascular events, a composite
      of cardiac death, myocardial infarction, and ischemia-driven target lesion
      revascularization (EES 7.7% vs. paclitaxel-eluting stent 16.4%, P = 0.056).
      Treatment with EES also resulted in a trend toward lower rates of cardiac death
      and numerically lower rates of myocardial infarction, ischemia-driven target
      lesion revascularization, and stent thrombosis. Overall, this study reports
      numerically fewer clinical events in patients treated with EES at 4-year follow
      up, which is consistent with results from earlier follow-up.

PMID- 20824771
TI  - Rescue angioplasty for failed fibrinolysis--long-term follow-up of a large
      cohort.
AB  - BACKGROUND: Fibrinolysis remains an important treatment for ST-elevation
      myocardial infarction, but fails to achieve adequate reperfusion in a significant
      proportion of cases. "Rescue" angioplasty is seen as the preferred treatment
      strategy in most contemporary centers although the literature provides
      conflicting evidence. METHODS: We retrospectively reviewed all cases of rescue
      angioplasty performed at our cardiothoracic center from July 1999 to June 2008.
      The diagnosis of failed lysis was made on the basis of an ECG demonstrating
      failure of ST segment resolution >50% at 90 min. Periprocedural data was taken
      from a dedicated procedural database and mortality data obtained from the UK
      Office of National Statistics. RESULTS: A total of 316 cases were performed.
      Patients were aged 61 +/- 11 years. Thirty-day mortality was 8.9%. Thirty-day
      mortality in those presenting with cardiogenic shock was 50%, and in those
      requiring blood transfusion was also 50%. Thirty day mortality in those with TIMI
      III flow at the end of the procedure was significantly less than in those in whom
      this was not the case (6.6% vs. 23.3%; P < 0.001). One year mortality for the
      entire cohort was 10.1%. Longer-term follow-up revealed after 5.2 +/- 2.3 years,
      survival in this cohort was 83%. Significant bleeding requiring blood transfusion
      occurred in 2.5% of cases. CONCLUSIONS: We have shown that rescue angioplasty can
      be performed with good procedural success rates and excellent long-term results.
      Limiting bleeding complications and achieving TIMI III flow appear to be major
      determinants of achieving good long term results.

PMID- 20824772
TI  - A case of mistaken identity: persistent sciatic artery stenosis as a cause of
      critical limb ischemia.
AB  - Critical limb ischemia (CLI) is the most severe manifestation of peripheral
      arterial disease (PAD) and is defined as leg pain that occurs at rest, tissue
      ulceration, or gangrene. Initial diagnostic testing is often focused on
      localizing the level or site of atherosclerotic narrowing and determining the
      severity of ischemia, usually with disease noted below the knee. This report
      highlights a case of CLI in a patient with an arterial stenosis in an anatomic
      variant, a persistent sciatic artery. As more endovascular procedures are being
      done by cardiologists, knowledge of aberrant anatomy is essential in the approach
      to diagnosis and treatment of patients with PAD. (c) 2011 Wiley-Liss, Inc.

PMID- 20824773
TI  - Long-term outcomes of elective drug-eluting stenting of the unprotected left main
      coronary artery in patients with normal left ventricular function.
AB  - OBJECTIVES: To evaluate the early and long-term outcomes of patients with normal
      left ventricular function who undergo elective unprotected left main coronary
      artery (ULMCA) percutaneous coronary intervention (PCI) with drug-eluting stents
      (DES). BACKGROUND: Although the standard of care for patients with ULMCA disease
      is coronary artery bypass surgery, the current guidelines recommend PCI in
      clinical conditions that predict an increased risk of adverse surgical outcomes.
      The long-term outcomes of patients with low risk of adverse surgical outcomes who
      undergo PCI are unknown. METHODS: Data from a multicenter international registry,
      which included 221 consecutive patients from four institutions with normal left
      ventricular function who underwent elective ULMCA PCI with DES from 2002 to 2009,
      were collected. RESULTS: There was no cardiac death, Q-wave myocardial
      infarction, target lesion revascularization (TLR), stent thrombosis, or stroke
      within the first 30 days. Seven (3%) patients had periprocedural myocardial
      infarction. Follow-up angiography was performed in 136 (62%) patients. Kaplan
      Meier event-free survival curves at 1 year for cardiac death and TLR rates were
      97.7% +/- 1.0% and 92.9% +/- 1.8%, respectively. At the mean follow-up of 44.8 +/
      22.8 months, the event-free rates for cardiac death and TLR were 95.5% +/- 1.5%
      and 88.9% +/- 2.3%, respectively. Multivariate analyses identified the predictors
      of cardiac death: age >= 75 years (P = 0.015) and history of myocardial
      infarction (P = 0.017). CONCLUSIONS: Elective ULMCA PCI with DES in patients with
      normal left ventricular function is safe and effective with excellent short-term
      outcomes and favorable long-term outcomes and may be a viable option for low-risk
      patients with normal left ventricular function.

PMID- 20824775
TI  - Development of NIPBL locus-specific database using LOVD: from novel mutations to
      further genotype-phenotype correlations in Cornelia de Lange Syndrome.
AB  - The establishment of Locus Specific Databases (LSDB) is a crucial aspect for the
      Human Genetics field and one of the aims of the Human Variation Project. We
      report the development of a publicly accessible LSDB for the NIPBL gene
      (http://www.lovd.nl/NIPBL) implicated in Cornelia de Lange Syndrome (CdLS). This
      rare disorder is characterized by developmental and growth retardation, typical
      facial features, limb anomalies, and multiple organ involvement. Mutations in the
      NIPBL gene, the product of which is involved in control of the cohesion complex,
      account for over half of the patients currently characterized. The NIPBL LSDB
      adopted the Leiden Open Variation database (LOVD) software platform, which
      enables the comprehensive Web-based listing and curation of sequence variations
      and associated phenotypical information. The NIPBL-LOVD database contains 199
      unique mutations reported in 246 patients (last accessed April 2010). Information
      on phenotypic characteristics included in the database enabled further genotype
      phenotype correlations, the most evident being the severe form of CdLS associated
      with premature termination codons in the NIPBL gene. In addition to the NIPBL
      LSDB, 50 novel mutations are described in detail, resulting from a collaborative
      multicenter study.

PMID- 20824776
TI  - On genomic DNA paradigms, research publications, and scholarly inquiry.

PMID- 20824777
TI  - Learning curve for competency in flexible laryngoscopy.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of our study was to identify the number of
      attempts required to attain competency in performing flexible laryngoscopy. STUDY
      DESIGN: Cross-sectional prospective study. METHODS: Fifteen medical students were
      recruited to perform flexible laryngoscopy on a mannequin. Each participant was
      given unlimited time and attempts to perform the procedure until considered
      competent by the evaluator for two consecutive attempts. Three evaluators used a
      flexible laryngoscopy checklist to score performance on each step of the
      procedure. Time required to perform the procedure was recorded, as well as number
      of times the scope hit the mucosa. The criteria for attaining competence were
      achieving a minimum score of 3 out of 5 on all the items of the checklist and
      being deemed competent by the evaluator. RESULTS: A total of 105 flexible
      laryngoscopies were performed by 15 medical students. A mean of six attempts
      (range, 2-17) were necessary for a medical student to become competent in
      performing flexible laryngoscopy. An 80% probability of becoming competent was
      achieved with the 14th attempt. An inverse relationship was noted between the
      number of times the scope hit the mucosa and the probability of being competent.
      The time taken to perform the procedure decreased with increasing number of
      attempts. CONCLUSIONS: Our results suggest that it takes six attempts on average
      for a novice to become competent in performing flexible laryngoscopy. This
      finding has implications for residency programs because it indicates the learning
      curve can be overcome in the laboratory rather than with patients. Laryngoscope,
      2010.

PMID- 20824778
TI  - Rhinitis medicamentosa as a cause of increased intraoperative bleeding.
AB  - Rhinitis medicamentosa occurs with repeated and prolonged use of topical
      decongestants. The resultant reduced ability to respond to decongestants mediated
      via enlarged capillary endothelial gaps can lead to profuse bleeding during
      turbinate surgery. We recommend that patients with rhinitis medicamentosa be
      weaned off topical decongestants prior to elective turbinate surgery to minimize
      this complication. The management of rhinitis medicamentosa and a case of
      intraoperative hemorrhage are presented.

PMID- 20824779
TI  - Gentamicin alters nitric oxide production in semicircular canals and otolith
      organs.
AB  - OBJECTIVES/HYPOTHESIS: Intratympanic application of gentamicin is an important
      therapeutic option to control vertigo spells in Meniere's disease. Low doses
      eliminate the function of semicircular canal ampullae (SCCA) and saccule in most
      patients, although utricular function is maintained in many cases. Local
      alteration in free radical production might be responsible for these differences.
      Therefore, the gentamicin-induced nitric oxide (NO) production was determined in
      an animal model using separate organ cultures of SCCA, saccule, and utricle.
      STUDY DESIGN: Prospective pilot study in male guinea pigs. METHODS: SCCA,
      saccule, and utricle of 28 guinea pigs were isolated and incubated separately for
      6 hours in cell culture medium. Gentamicin was administered in two different
      concentrations (0.4 mg/mL and 0.8 mg/mL) to organ cultures of 16 animals. Tissues
      from 12 animals were used as controls. Nitric oxide was quantified by
      chemiluminescence. RESULTS: Gentamicin led to an NO increase of about 70% in the
      saccule, an NO reduction of more than 70% in SCCA, and an NO reduction of 36% in
      the utricle. CONCLUSIONS: The selective effects of gentamicin on the NO
      production in the different sensory areas of the vestibular organ have to be
      taken into account in the therapy of Meniere's disease.

PMID- 20824780
TI  - Coblation removal of laryngeal Teflon granulomas.

PMID- 20824781
TI  - Antibiotic prophylaxis in the management of complex midface and frontal sinus
      trauma.
AB  - OBJECTIVES/HYPOTHESIS: Although mandible trauma has been studied extensively,
      there is no standard for use of pre- and postoperative antibiotics in other
      facial trauma. We sought to determine whether antibiotic strategies have an
      effect on infection rates. STUDY DESIGN: Retrospective chart review and cohort
      analysis. METHODS: Patients seen by the otolaryngology service for traumatic
      facial injuries between January 1, 2003 and January 1, 2009, were included in a
      retrospective cohort analysis (N = 223). All patients received perioperative
      antibiotic coverage. Isolated mandible fractures were excluded. RESULTS: Patient
      demographics were 73% male and 27% female, with an average age of 35 years
      (range, 8-81 years). The most common causes of trauma were assault (39%), motor
      vehicle accidents (28%), and falls (11%). The overall infection rate was 9%.
      There was no significant difference (P = .248) between infection rates for
      patients in each antibiotic group (preoperative, postoperative, pre- and
      postoperative, only perioperative). Infection rate was independently correlated
      with both number of fractures (P < .0001) and open fracture wounds (P = .034).
      There was no significant difference in infection rate between patients who
      received only perioperative antibiotics and those who received additional
      antibiotics (P = .997). However, the cohort with the most antibiotic use (pre-,
      peri-, and postoperative) had more severe facial injuries than the cohort that
      received only perioperative antibiotics. CONCLUSIONS: The use of additional
      antibiotics outside the perioperative timeframe does not reduce the rate of
      postoperative infections; however, such antibiotic use may be warranted in cases
      of severe facial trauma with multiple open fracture wounds. Laryngoscope, 2010.

PMID- 20824782
TI  - Management of giant sialoliths: review of the literature and preliminary
      experience with interventional sialendoscopy.
AB  - OBJECTIVES/HYPOTHESIS: To report our experience with management of giant salivary
      stones via a combined approach technique using salivary endoscopy (CA) and
      results of a review of current literature related to giant salivary stones. STUDY
      DESIGN: Retrospective case series. METHODS: An institutional review board
      approved chart review was performed on patients managed with a CA to treat giant
      salivary stones (>=15 mm). In addition, we reviewed the English literature from
      1942 to 2009. RESULTS: Table 1 consists of 54 stones; 47 of which were identified
      during the review of literature and 7 from our case series. Of those 47 stones,
      23 were hilar in location, 23 were glandular in location, and 1 stone was missing
      data. The gland preservation rate in the 47 reported stones was 57% (17/30).
      Among patients where gland resection was reported, the majority of the patients
      (12/13) had hilar glandular stones. Only one patient with a ductal stone had a
      gland resection. In our series, CA enabled a gland preservation rate of 86%
      (6/7). Among these patients, stone location was hilar glandular in six (86%) and
      ductal in one (14%). The mean size of stones from the literature review was 35 mm
      and from our series was 19 mm. CONCLUSIONS: Our review reflects current treatment
      recommendations for giant stones, i.e., transoral sialolithotomy for ductal
      stones and gland resection for hilar glandular stones. Our preliminary experience
      with CA for giant stones suggests improved gland preservation rates (86% vs. 57%)
      independent of stone location and with preservation of salivary function.

PMID- 20824783
TI  - Human papillomavirus and WHO type I nasopharyngeal carcinoma.
AB  - OBJECTIVES: Nasopharyngeal carcinoma (NPC) is a rare cancer in the United States.
      An association between NPC and Epstein-Barr virus (EBV) is well-established for
      World Health Organization (WHO) types II and III (WHO-II/III) NPC but less well
      established for WHO type I (WHO-I) NPC. Given the rise in oropharyngeal tumors
      positive for high-risk human papillomavirus (HPV) and the unique biology of WHO-I
      NPC, we examined the relationship between HPV and WHO-I NPC. STUDY DESIGN:
      Retrospective case-comparison study. METHODS: A search of a large
      multidisciplinary cancer center tumor registry identified 183 patients seen from
      January 1999 to December 2008 with incident NPC and no prior cancer. Available
      paraffin-embedded tumor specimens (N = 30) were analyzed for oncogenic HPV status
      by in situ hybridization (ISH) and polymerase chain reaction (PCR) for HPV-16 and
      HPV-18; EBV status by ISH; and p16 expression by immunohistochemistry.
      Demographic parameters, including race and smoking, were obtained from the
      medical records. RESULTS: Among the 18 WHO-I NPC patients, 66% (N = 12) were
      smokers and 17% (N = 3) Asian; among the 165 WHO-II/III NPC patients, 44% (N =
      73) were smokers and 24% (N = 39) Asian. Eight WHO-I NPC patients had available
      paraffin blocks; five of six were HPV-16-positive by PCR and four of eight were
      HPV-positive by ISH; only two of eight (25%) were EBV-positive. Twenty-two WHO
      II/III NPC patients had available paraffin blocks; only 1 was HPV-positive by
      ISH, and 13 of 22 (60%) were EBV-positive. CONCLUSIONS: These results suggest
      that WHO-I NPC is associated with oncogenic HPV, although larger studies are
      needed to verify these findings. Laryngoscope, 2010.

PMID- 20824784
TI  - Pediatric sleep apnea and craniofacial anomalies: a population-based case-control
      study.
AB  - OBJECTIVE: To investigate the association between craniofacial anomalies and
      diagnosis with obstructive sleep apnea (OSA) in a large, population-based sample
      of children. DESIGN: Retrospective case-control study. METHODS: Cases of OSA (n =
      1,203) were identified by International Classification of Diseases-9 codes
      consistent with OSA in the 1987-2003 Washington State inpatient discharge
      database among children <=18 years of age and born in Washington state. For each
      case, five controls without OSA (n = 6,015) were randomly selected from the
      remaining Washington State births, frequency matched by birth year. Congenital
      anomaly diagnoses and covariates were extracted from discharge data for all
      inpatient hospitalizations during the study period and linked birth certificate
      data. Multiple logistic regression was used to calculate adjusted odds ratios
      (OR) and 95% confidence intervals (CI) for the associations between congenital
      anomalies (including subgroups) and OSA. RESULTS: An OSA diagnosis was strongly
      associated with the presence of any craniofacial anomaly (adjusted OR 38, 95%CI
      [24, 60]) and, in particular, with orofacial cleft (adjusted OR 40, 95%CI [17,
      94]) and Down syndrome (adjusted OR 51, 95%CI [20, 128]). OSA was less associated
      with any noncraniofacial malformation (adjusted OR 4.1, 95%CI [3.1, 5.3]), which
      may reflect the relatively small effect of inpatient exposure bias in the
      associations above. CONCLUSIONS: The presence of congenital craniofacial
      anomalies is strongly associated with inpatient diagnosis of OSA. These findings
      persist even after control of major potential biases. Parents and clinicians
      should consider screening for OSA among children with craniofacial anomalies.

PMID- 20824785
TI  - Development and pilot testing of an objective structured clinical examination
      (OSCE) on hoarseness.
AB  - OBJECTIVES: To develop a valid and reliable tool for an objective structured
      clinical examination (OSCE) on hoarseness. To pilot-test the feasibility by
      assessing residents' clinical skills in various core competencies while assessing
      hoarseness on a standardized patient (SP). STUDY DESIGN: Educational tool
      development. METHODS: The OSCE checklists were developed using modified Delphi
      technique after obtaining feedback from faculty involved in providing care to
      hoarseness patients. SP-based and rest stations were created to assess clinical
      skills. Twelve Otolaryngology-Head and Neck Surgery residents participated in the
      study. Video recordings of residents' performance and their written documentation
      were rated by faculty members. RESULTS: The OSCE that we developed is a valid
      method of assessing residents' clinical skills for evaluating hoarseness. Senior
      residents performed better in all of the tasks such as obtaining history and
      performing a physical exam on an SP, ability to perform flexible laryngoscopy on
      a mannequin, and interpretation of radiologic findings. Internal consistency
      assessed by Cronbach's alpha as measure of inter-item reliability was 0.92 for
      laryngoscopic station and 0.95 for radiology station. CONCLUSIONS: This OSCE can
      be effectively used for the objective assessment of clinical competency in
      hoarseness. Our pilot study evaluated multiple competencies on a single occasion,
      including medical knowledge, patient care, professionalism, and communication and
      interpersonal skills. Clinical competence in history taking, physical
      examination, flexible fiber-optic laryngoscopy, and ability to interpret
      radiologic findings improved with increasing year of training. This OSCE provides
      targeted assessment of practice-based learning and feedback for improvement of
      clinical performance.

PMID- 20824786
TI  - Acute airway obstruction in cervical spinal procedures with bone morphogenetic
      proteins.
AB  - OBJECTIVES: Bone morphogenetic proteins (BMP) used in anterior cervical spinal
      procedures causes an inflammatory response resulting in upper-airway obstruction
      between postoperative days 2 to 7. The purpose of this study is to determine the
      incidence and severity of complications associated with use of BMP. STUDY DESIGN:
      Retrospective cohort study. METHODS: This is a retrospective study of 260
      patients who underwent cervical spinal procedures with BMP from 2004 to 2009 and
      a control group of 515 patients who underwent cervical spinal procedures without
      BMP during the same period at a tertiary care institution. The two groups were
      compared on hospital length of stay (LOS), hospital charges, incidence of airway
      obstruction, unplanned intubations after surgery, tracheotomies, intensive care
      unit (ICU) admissions, hoarseness, dyspnea, respiratory failure, dysphasia,
      dysphagia, readmissions, and need for percutaneous endoscopic gastrostomy (PEG)
      tubes. RESULTS: Patients who underwent cervical spine procedures with BMP were
      noted to have significantly longer hospital stays (P = .001) and higher hospital
      charges (P = .001) than the control group. Tracheotomies (P = .024), unplanned
      intubations after surgery (P = .003), dysphagia (P = .001), dyspnea (P = .001),
      respiratory failure (P = .001), hospital readmissions (P = .040), ICU admissions
      (P = .001), and 90-day mortality rates (P = .047) were increased for the BMP
      group. CONCLUSIONS: The use of BMP in anterior cervical spinal procedures results
      in acute airway obstruction due to an extensive soft-tissue inflammatory reaction
      that is most likely to occur 2 to 7 days after surgery. The increased incidence
      of unplanned intubations and tracheotomies demonstrates the risk associated with
      BMP in cervical spinal procedures.

PMID- 20824787
TI  - Early versus late injection medialization for unilateral vocal cord paralysis.
AB  - OBJECTIVES: To evaluate whether the timing of early (<=6 months from time of
      nerve injury) vs. late (>6 months) injection medialization laryngoplasty impacts
      the need for subsequent open-neck reconstruction to restore vocal function in
      patients with unilateral vocal cord paralysis. STUDY DESIGN: Retrospective chart
      review. METHODS: A total of 112 outpatient or hospitalized adults with dysphonia
      resulting from postsurgical or idiopathic unilateral vocal cord paralysis were
      identified who were injected as initial treatment within 1 year of onset of their
      paralysis. All subjects underwent awake, transoral, paraglottic injection with
      absorbable hyaluronic-acid gel. Patients with documented recovery of vocal cord
      mobility (22), active disease directly affecting the recurrent laryngeal nerve
      (8), <3 months of follow-up after injection (time for gel to be reabsorbed) (34),
      or deaths within 1 year after the onset of paralysis (13) were excluded, leaving
      a study population of 35 patients. RESULTS: Twenty of 32 (62.5%) patients with
      early injection medialization maintained an adequate voice, obviating the need
      for open-neck phonosurgical reconstruction; their follow-up from onset of
      paralysis ranged from 4.0 to 41.8 months (mean 15.2). None of the three patients
      undergoing late injection (>6 months postparalysis) avoided phonosurgical
      reconstruction (P = .03, chi2 test). CONCLUSIONS: Patients receiving early
      injection medialization for vocal cord paralysis were less likely to require
      transcervical reconstruction. We believe that early medialization creates a more
      favorable vocal cord position for phonation that can be maintained by synkinetic
      reinnervation, in contrast to the final position of a lateralized vocal cord
      being determined solely by reinnervation.

PMID- 20824788
TI  - Hearing loss alters quantal release at cochlear nucleus stellate cells.
AB  - OBJECTIVES/HYPOTHESIS: Auditory nerve synapses in ventral cochlear nucleus end on
      two principal cell types, bushy and stellate cells. Although the effects of
      hearing loss on bushy cells have been well studied, little is known about the
      effects of hearing loss on synaptic input to the stellate cells. Based on prior
      observations in bushy cells, we hypothesized that noise-induced hearing loss
      (NIHL) would decrease quantal release onto stellate cells. STUDY DESIGN:
      Prospective, randomized animal study. METHODS: CBA/CaJ mice were exposed for 2
      hours to 98 dB sound pressure level (SPL) 8- to 16-kHz noise to produce a
      temporary threshold shift (TTS) or 114 dB SPL to produce a permanent threshold
      shift (PTS). Spontaneous miniature excitatory postsynaptic currents (mEPSCs) were
      then measured in stellate cells in brain slices of the cochlear nucleus. RESULTS:
      Click auditory brainstem evoked response thresholds were elevated by 35 dB in
      both TTS and PTS mice. Spontaneous mEPSC frequency was found to be five-fold
      higher than normal in stellate cells of TTS mice and three-fold higher in PTS
      mice. The mEPSC amplitude was also larger in PTS mice. The mEPSC time course was
      not different between experimental and control groups. CONCLUSIONS: The dramatic
      increase in mEPSC frequency after NIHL was not expected. The increase in mEPSC
      amplitude in PTS mice suggests a postsynaptic remodeling process. Both of these
      effects could contribute to increased spontaneous firing in the cochlear nucleus
      in the absence of sound. Our results also suggest that hearing loss may have
      different effects at auditory nerve synapses on bushy and stellate cells in the
      VCN.

PMID- 20824789
TI  - Prognosis of Ramsay Hunt syndrome presenting as cranial polyneuropathy.
AB  - OBJECTIVES/HYPOTHESIS: Ramsay Hunt syndrome is known to be accompanied with
      cranial polyneuropathy very occasionally. We reviewed our experience to analyze
      the clinical manifestations and prognosis of these cases. STUDY DESIGN:
      Retrospective review. METHODS: Eleven patients with Ramsay Hunt syndrome
      presenting as cranial polyneuropathy between 1999 and 2009 were included in this
      study retrospectively. All patients were treated with systemic steroids and
      antiviral agents. Assessment of recovery from facial nerve palsy (FNP) using the
      House-Brackmann (HB) grading system was performed, and the follow-up period was 4
      to 28 months. RESULTS: The patient numbers for the initial degree of FNP were
      five for HB grade II, one for grade III, two for grade IV, and three for grade V.
      The cochleovestibular nerve was involved in 10 cases, and hearing loss was
      observed in nine patients. Other involved cranial nerves were IX in seven cases,
      X in five cases, V in three cases, and III/XII in one case each. Antiviral agents
      and steroids were administered within 3 days after the onset of symptoms for
      about 1 to 2 weeks in most cases. After the treatment the degree of FNP improved
      to HB grade I or II in nine of 11 patients (81.8%). Symptoms of other cranial
      nerves also improved in most patients, whereas recovery for hearing loss showed
      poor results. CONCLUSIONS: Ramsay Hunt syndrome associated with cranial
      polyneuropathy has a good prognosis for FNP and other cranial nerve palsies with
      a combination therapy of antiviral agents and steroids, but not for recovery of
      hearing loss.

PMID- 20824790
TI  - Presence of olfactory event-related potentials predicts recovery in patients with
      olfactory loss following upper respiratory tract infection.
AB  - OBJECTIVES/HYPOTHESIS: The aim of the present study was to evaluate the course of
      olfactory dysfunction in patients with olfactory loss following infections of the
      upper respiratory tract. STUDY DESIGN: Prospective cohort. METHODS: A total of 27
      patients were included; each patient was evaluated twice. Psychophysical testing
      of olfactory function was performed with the Sniffin' Sticks test and
      chemosensory functions with event-related potential (ERP). RESULTS: At T1, 15
      patients were considered hyposmic, 12 as anosmic. Accordingly, nine and 27
      patients demonstrated olfactory ERP. At T2, 16 and 11 patients were considered as
      hyposmic and anosmic, and 11 demonstrated olfactory ERP. Analysis of variance did
      not show significant differences for any parameters between T1 and T2: threshold,
      discrimination, identification (TDI) scores at the Sniffin' Sticks and amplitudes
      and latencies of N1 and P2 in the ERP. However, seven patients demonstrated an
      increase of more or equal to six points at the TDI score, indicating significant
      improvement. Four of the seven patients had olfactory ERP at T1 (57%); of those
      patients who did not show improvement, five of 20 (25%) exhibited olfactory ERP.
      Thus, the presence of olfactory ERP predicts a positive evolution of olfactory
      function with a relatively high specificity of 83%. CONCLUSIONS: The current
      findings clearly confirm earlier results on recovery rate of postinfectious
      olfactory loss. The new finding is that the presence of olfactory ERP at the
      first consultation is also a positive predictive factor of a favorable outcome in
      this disease.

PMID- 20824791
TI  - Laryngeal framework reconstruction using titanium mesh in glottic cancer after
      frontolateral vertical partial laryngectomy.
AB  - OBJECTIVES: To investigate the feasibility and efficacy of laryngeal framework
      reconstruction using titanium mesh in patients with glottic cancer after
      frontolateral vertical partial laryngectomy. STUDY DESIGN: Prospective study.
      METHODS: Defect of laryngeal framework, caused by frontolateral vertical partial
      laryngectomy in nine patients with T2 or T3 squamous cell carcinoma of glottic,
      were reconstructed with titanium mesh from 2007 to 2009. Computed tomography (CT)
      and fiberscopic examinations were performed at two weeks and three months
      postoperatively. RESULTS: No aspiration and laryngeal stenosis was observed in
      the nine patients. CT scanning showed that titanium mesh was fastened well
      without displacement and deformity and that there was no laryngeal stenosis.
      Fiberscopic inspection showed that the larynx lumen was maintained well without
      stricture, shrinkage, and necrosis. No titanium mesh was exposed to the larynx
      lumen. CONCLUSIONS: Titanium mesh was a good alternative for reconstruction of
      the laryngeal framework. It provided adequate structural support to maintain
      airway patency.

PMID- 20824792
TI  - European Society for Clinical Evaluation of Balance Disorders: discussion about
      dual-task conditions combining postural control with cognitive tasks.

PMID- 20824793
TI  - Balloon catheter technology in rhinology: Reviewing the evidence.
AB  - Balloon catheter technology (BCT) for management of paranasal sinus inflammatory
      disease was introduced to otolaryngology in 2005. Since its introduction, BCT has
      been a subject of considerable controversy with proponents for and against
      adoption of the technology. Balloon procedures have been promoted as a less
      invasive alternative to endoscopic sinus surgery that results in reduced pain and
      quicker recovery. The technology and its promotion have generated significant
      press coverage and interest by the lay public looking for new solutions for
      sinonasal problems. Over time, alternate balloon devices have been advocated for
      operating room and office-based sinus ostia dilatation. This contemporary review
      will evaluate the existing evidence on the available balloon devices. The frank
      strengths and weaknesses of the peer-reviewed literature will be highlighted. The
      potential complications unique to balloon catheters and radiation exposure from
      fluoroscopy will also be discussed.

PMID- 20824795
TI  - Clinical images: bead-like gouty tophi in the hand and foot.

PMID- 20824794
TI  - A novel germline CDKN1B mutation causing multiple endocrine tumors: clinical,
      genetic and functional characterization.
AB  - Multiple endocrine neoplasia (MEN) syndromes are characterized by tumors
      involving two or more endocrine glands. Two MEN syndromes have long been known:
      MEN1 and MEN2,caused by germline mutations in MEN1 or RET, respectively.
      Recently, mutations in CDKN1B,encoding the cyclin-dependent kinase (Cdk)
      inhibitor p27, were identified in patients having a MEN1-like phenotype but no
      MEN1 gene mutations. Currently, the molecular mechanisms mediating the role of
      p27 in tumor predisposition are ill defined. We here report a novel germline
      missense variant in CDKN1B (c.678C>T, p.P69L) found in a patient with multiple
      endocrine tumors. We previously reported a nonsense p27 mutation (c.692G>A,
      p.W76X) in two patients with MEN1-like phenotype. Functional assays were used to
      characterize p27P69L and p27W76X in vitro. We show that p27P69L is expressed at
      reduced level and is impaired in both binding toCdk2 and inhibiting cell growth.
      p27W76X, which is mislocalized to the cytoplasm, can no longer efficiently bind
      Cyclins-Cdks, nor inhibit cell growth or induce apoptosis. In the patient's tumor
      tissues, p27P69L associates with reduced/absent p27 expression and in one tumor
      with loss-of heterozygosity.Our results extend previous findings of CDKN1B
      mutations in patients with MEN1-related states and support the hypothesis of a
      tumor suppressor role for p27 in neuroendocrine cells.

PMID- 20824796
TI  - Trends in hospitalizations for Pneumocystis jiroveci pneumonia among patients
      with rheumatoid arthritis in the US: 1996-2007.

PMID- 20824797
TI  - Fibroblast growth factor 2 and platelet-derived growth factor, but not platelet
      lysate, induce proliferation-dependent, functional class II major
      histocompatibility complex antigen in human mesenchymal stem cells.
AB  - OBJECTIVE: To document the specificity and the mechanism of induction of a novel
      class II major histocompatibility complex (MHC) antigen by mitogenic growth
      factors in human mesenchymal stem cells (MSCs) expanded in vitro for
      translational applications. METHODS: Expression of class II MHC molecules was
      measured in human MSCs and differentiated cells expanded in the presence of
      fibroblast growth factor 2 (FGF-2), platelet-derived growth factor BB (PDGF-BB),
      human platelet lysate, or interferon-gamma (IFNgamma). The roles of cell
      proliferation and growth factor-induced signaling pathways were investigated as
      well as the class II MHC assembly machinery and functional capacity. RESULTS: FGF
      2 and, to a lesser extent, PDGF-BB induced in adult human MSCs the expression of
      HLA-DR (normally induced by inflammatory cytokines), which was able to stimulate
      CD4+ T cells via superantigen binding. In contrast to IFNgamma, FGF induced HLA
      DR expression only in human MSCs proliferating under its mitogenic effect and not
      in mouse MSCs or in differentiated human cells. Although it induced cell
      proliferation, human platelet lysate did not cause HLA-DR expression in human
      MSCs. HLA-DR expression occurred following FGF-specific binding to its
      receptor(s), mainly FGF receptor 1, without inducing IFNgamma or tumor necrosis
      factor alpha expression. Both MAPK/ERK-1/2 and phosphatidylinositol 3-kinase/Akt
      controlled cell proliferation and HLA-DR expression, but only MAPK/ERK-1/2
      controlled the induction of the class II MHC transcription activator protein
      CIITA, the major determinant of HLA-DR transcription. CONCLUSION: The induction
      of functional HLA-DR in proliferating progenitor MSCs is a property of human MSCs
      that have been expanded with mitogenic growth factors. This has potential
      biologic significance in the regulation and/or protection of progenitor cell
      subpopulations under sustained mitogenic proliferation and needs to be taken into
      account when expanding MSCs for use in in vivo applications.

PMID- 20824798
TI  - Effects of community-deliverable exercise on pain and physical function in adults
      with arthritis and other rheumatic diseases: a meta-analysis.
AB  - OBJECTIVE: To use the meta-analytic approach to determine the effects of
      community-deliverable exercise on pain and physical function in adults with
      arthritis and other rheumatic diseases (AORD). METHODS: Data sources consisted of
      6 electronic databases, cross-referencing from retrieved studies and expert
      review. Study selection included 1) randomized controlled trials; 2) >= 1
      exercise intervention group; 3) community-deliverable exercise interventions >= 4
      weeks in duration; 4) control group; 5) adults ages >= 18 years with rheumatoid
      arthritis, osteoarthritis, fibromyalgia, lupus, gout, or ankylosing spondylitis;
      6) published and unpublished studies; 7) studies published in any language
      between January 1, 1980, and January 1, 2008; and 8) data available for pain
      and/or physical function. Data abstraction included dual coding by 2 of the
      authors. Standardized effect sizes (g) and random-effects models were used to
      pool pain and physical function outcomes. Data were analyzed according to per
      protocol and intent-to-treat (ITT) results. The minimally clinically important
      difference (MCID) and number needed to treat (NNT) were also calculated. RESULTS:
      Thirty-three studies representing 3,180 men and women (1,857 exercise, 1,323
      control) with rheumatoid arthritis, osteoarthritis, and fibromyalgia were
      included. Statistically significant and clinically important improvements were
      observed for pain (per-protocol g = -0.37 [95% confidence interval (95% CI) 
      0.53, -0.21], MCID -18%; ITT g = -0.20 [95% CI -0.33, -0.07], MCID -9%, NNT 9)
      and physical function (per-protocol g = 0.37 [95% CI 0.21, 0.52], MCID 15%; ITT g
      = 0.34 [95% CI 0.25, 0.43], MCID 10%, NNT 5). CONCLUSION: Community-deliverable
      exercise improves pain and physical function in adults with the types of AORD
      included in the analysis. Dose-response as well as studies in those with other
      types of AORD is needed.

PMID- 20824799
TI  - Responsiveness of the ABILHAND questionnaire in measuring changes in rheumatoid
      arthritis patients.
AB  - OBJECTIVE: ABILHAND is a Rasch-built questionnaire that measures manual ability
      in rheumatoid arthritis (RA) patients. This study aimed to examine the test
      retest reliability and the responsiveness of ABILHAND in RA patients. METHODS:
      Eighty-eight patients underwent 3 evaluations: the first evaluation was at
      baseline (time 1), the second was 2 weeks later (time 2), and the third was 1
      year later (time 3). Disease activity was assessed using the Disease Activity
      Score in 28 joints using the C-reactive protein level (DAS28-CRP). Patients rated
      the intensity of their RA-related pain using a 100-mm visual analog scale for
      pain and completed questionnaires based on their activity limitations (ABILHAND
      and the Health Assessment Questionnaire) and quality of life. RESULTS: The
      responsiveness analyses were conducted by using global, group, and individual
      approaches. The global approach showed significant differences between the time 1
      and time 3 scores of the DAS28-CRP (P = 0.04) and ABILHAND (P = 0.04). Based on
      the changes in disease activity scores and the European League Against Rheumatism
      response criteria, the sample was divided into 3 groups: deteriorated, stable,
      and improved. The mean +/- SD changes in manual ability were higher in the
      deteriorated (-1.23 +/- 1.53 logit) and in the improved (1.22 +/- 2.06 logits)
      groups than in the stable group (0.48 +/- 1.09 logit). The effect size and
      standardized response mean confirmed that observation. The minimal clinically
      important difference was assessed in each group of patients. CONCLUSION: The
      ABILHAND questionnaire exhibited responsiveness in detecting slight changes in RA
      patients. Therefore, the ABILHAND tool can be used to evaluate the functional
      status of RA patients in clinical trials and settings.

PMID- 20824800
TI  - Socioeconomic determinants of disability and depression in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To examine the relationship between functional limitation,
      socioeconomic inequality, and depression in a diverse cohort of patients with
      rheumatoid arthritis (RA). METHODS: The study design was cross-sectional and
      subjects were from the University of California, San Francisco RA Cohort.
      Patients were enrolled from 2 rheumatology clinics, an urban county public
      hospital and a university tertiary care medical center. Age, sex, race/ethnicity,
      disease activity, functional limitation, and medications were variables collected
      at clinical visits. The patient's clinic site was used as a proxy for his or her
      socioeconomic status. The outcome variable was depressive symptom severity
      measured by the Patient Health Questionnaire 9. Differences in characteristics
      between depressed and nondepressed patients were calculated using 2-sided t-tests
      or the Pearson's chi-square test. For the multivariate analysis, repeated
      measures with generalized estimating equations were used. RESULTS: There were
      statistically significant differences between depressed and nondepressed patients
      related to race/ethnicity, public versus tertiary care hospital rheumatology
      clinic, disability, and medications. In the multivariate analysis, increased
      functional limitation and public clinic site remained significantly associated
      with increased depression scores. A significant interaction existed between
      clinic site and disability. Mean depression scores rose more precipitously as
      functional limitation increased at the public hospital rheumatology clinic.
      CONCLUSION: There are disparities in both physical and mental health among
      individuals with low socioeconomic status. The psychological effects of
      disability vary in patients with RA such that a vulnerable population with
      functional limitations is at higher risk of developing depressive symptoms.

PMID- 20824801
TI  - Obesity and its measurement in a community-based sample of women with systemic
      lupus erythematosus.
AB  - OBJECTIVE: To determine the prevalence of obesity and evaluate how accurately
      standard anthropometric measures identify obesity among women with systemic lupus
      erythematosus (SLE). METHODS: Dual x-ray absorptiometry (DXA), height, weight,
      and waist and hip circumference measurements were collected from 145 women with
      SLE. Three anthropometric proxies of obesity (body mass index [BMI]>=30 kg/m2,
      waist circumference [WC]>=88 cm, and waist:hip ratio [WHR]>=0.85) were compared
      with a DXA-based obesity criterion. Correspondence between measures was assessed
      with Cohen's kappa. Receiver operating characteristic curves determined optimal
      cut points for each anthropometric measure relative to DXA. Framingham
      cardiovascular risk scores were compared among women who were classified as not
      obese by both traditional and revised anthropometric definitions, obese by both
      definitions, and obese only by the revised definition. RESULTS: Of the 145 women,
      28%, 29%, 41%, and 50% were classified as obese by WC, BMI, WHR, and DXA,
      respectively. Correspondence between anthropometric and DXA-based measures was
      moderate. Women misclassified by anthropometric measures had less truncal fat and
      more appendicular lean and fat mass. Cut points were identified for
      anthropometric measures to better approximate DXA estimates of percent body fat:
      BMI>=26.8 kg/m2, WC>=84.75 cm, and WHR>=0.80. Framingham risk scores were
      significantly higher in women classified as obese by either traditional or
      revised criteria. CONCLUSION: A large percentage of this group of women with SLE
      was obese. Substantial portions of women were misclassified by anthropometric
      measures. Utility of revised cut points compared with traditional cut points in
      identifying risk of cardiovascular disease or disability remains to be examined
      in prospective studies, but results from the Framingham risk score analysis
      suggest that traditional cut points exclude a significant number of at-risk women
      with SLE.

PMID- 20824802
TI  - Impact of systemic sclerosis on occupational and professional activity with
      attention to patients with digital ulcers.
AB  - OBJECTIVE: To evaluate the impact of systemic sclerosis (SSc; scleroderma) and
      digital ulcers (DUs) on daily living and professional activities. METHODS: We
      prospectively evaluated 189 SSc patients for employment status and disability
      during meetings of the French SSc patient association (n=86, 45.5%) or during
      hospitalization (n=103, 54.5%). RESULTS: Seventy-eight (41.2%) patients had
      diffuse SSc. The mean+/-SD age was 54+/-13 years, and the mean+/-SD disease
      duration was 9.3+/-8.4 years at the time of evaluation. Sixty (31.7%) patients
      had at least one DU. Assessed using the Health Assessment Questionnaire (mean+/
      SD 1.12+/-0.79 versus 1.39+/-0.84; P=0.001), the Cochin Hand Function Scale
      (mean+/-SD 20.2+/-18.3 versus 27.8+/-19.1; P<0.0001), and the Hospital Anxiety
      Scale (mean+/-SD 9.9+/-5 versus 8.5+/-4.2; P=0.04), global disability, hand
      disability, and anxiety, respectively, were significantly higher in patients with
      DUs than in others. Most patients reported a limitation in daily activities
      related to SSc, as assessed by a daily activity limitation scale (mean+/-SD 4.4+/
      2.9) and an increased need for help in the home. Patients reported needing mean+/
      SD 4+/-13.5 hours per month of paid household help related to SSc and mean+/-SD
      1.5+/-10 hours per month related to DUs, with significant differences between
      patients with or without DUs (P=0.004). Among the 113 patients in the workforce,
      67 (59.3%) were employed, 42 (37.2%) were employed full time, 36 (31.8%) received
      full disability pension, and 27 (23.9%) were on sick leave, with no difference
      between patients with or without DUs. CONCLUSION: SSc has a significant impact on
      activities of daily living and work disability. The need for external home help
      and disability are increased for those patients with DUs.

PMID- 20824803
TI  - Varus thrust in medial knee osteoarthritis: quantification and effects of
      different gait-related interventions using a single case study.

PMID- 20824805
TI  - Hyperuricemia and incident hypertension: a systematic review and meta-analysis.
AB  - OBJECTIVE: A novel rodent model and a recent randomized trial of hyperuricemic
      adolescents with hypertension suggest a pathogenetic role of uric acid in
      hypertension, but it remains unknown whether these findings would be applicable
      to adult populations where the larger disease burden exists. We conducted a
      systematic review and meta-analysis to determine if hyperuricemia was associated
      with incident hypertension, particularly in various demographic subgroups.
      METHODS: We searched major electronic databases using medical subject headings
      and keywords without language restrictions (through April 2010). We included
      prospective cohort studies with data on incident hypertension related to serum
      uric acid levels. Data abstraction was conducted in duplicate. We analyzed age,
      sex, and race subgroups. RESULTS: A total of 18 prospective cohort studies
      representing data from 55,607 participants were included. Hyperuricemia was
      associated with an increased risk for incident hypertension (adjusted risk ratio
      [RR] 1.41, 95% confidence interval [95% CI] 1.23-1.58). For a 1 mg/dl increase in
      uric acid level, the pooled RR for incident hypertension after adjusting for
      potential confounding was 1.13 (95% CI 1.06-1.20). These effects were
      significantly larger in younger study populations (P = 0.02) and tended to be
      larger in women (P = 0.059). Two studies suggested that the effect may also be
      larger among African American individuals. Furthermore, later publication year
      and US-based studies were significantly associated with a lower effect estimate
      (P values <0.02). CONCLUSION: Hyperuricemia is associated with an increased risk
      for incident hypertension, independent of traditional hypertension risk factors.
      This risk appears more pronounced in younger individuals and women.

PMID- 20824806
TI  - Malnutrition and quality of life in patients treated for oral or oropharyngeal
      cancer.
AB  - BACKGROUND: This study assessed whether malnourished patients score lower on
      quality of life after treatment for oral/oropharyngeal cancer. METHODS:
      Malnutrition (weight loss >= 10% in 6 months/ >= 5% in 1 month) and quality of
      life (European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire Core 30 questionnaire) were assessed cross-sectionally in patients
      treated for oral/oropharyngeal cancer. The interval after treatment varied from 1
      day to 3 years. The relationship between malnutrition and quality of life was
      analyzed univariately (Mann-Whitney U test) and multivariately (linear regression
      analyses). Statistical significance was set at p < .05. RESULTS: Prevalence of
      posttreatment malnutrition was 16% (18/115, 95% confidence interval [CI]: 9% to
      23%). Analyzed univariately, malnourished patients scored significantly worse on
      physical functioning (p = .007) and fatigue (p = .034) than well-nourished
      patients. Multivariate analysis revealed that malnutrition was significantly
      related to physical functioning (p = .015). CONCLUSIONS: Malnourished patients
      treated for oral/oropharyngeal cancer score lower on quality of life scales
      related to physical fitness.

PMID- 20824807
TI  - Nasal morbidity following endoscopic skull base surgery: a prospective cohort
      study.
AB  - BACKGROUND: Nasal morbidity following skull base surgery necessitates follow-up
      for postoperative care. We describe nasal morbidity following endoscopic skull
      base surgery. METHODS: Patient and operative data and postoperative subjective
      and objective measures of morbidity were prospectively collected for 1 year. Time
      to absence of crusting and remucosalization were determined. Risk factor analyses
      for crusting and nasal discharge were performed. RESULTS: Nasal crusting (98%)
      and discharge (46%) were the most common postoperative symptoms. Median time to
      absence of crusting was 101.0 days, with longer times for complex cases (p =
      .033) but not for patients with septal flaps or fat grafts. Median time to
      remucosalization after nasoseptal flap was 89.0 days. There were no risk factors
      for crusting, although surgical complexity was a risk factor for postoperative
      discharge (odds ratio [OR] = 5.17). CONCLUSIONS: Nasal morbidity following
      endoscopic skull base surgery is common and may be affected by surgical
      complexity and use of the nasoseptal flap.

PMID- 20824808
TI  - Extracapsular tumor extension in cervical lymph nodes: reconciling the literature
      and seer data.
AB  - BACKGROUND: Extracapsular extension (ECE) of disease from cervical lymph nodes
      (LNs) is an important prognostic factor for head and neck cancers; moreover, the
      presence of ECE has been shown to be a criterion for the addition of chemotherapy
      to postoperative radiation. METHODS: We reviewed the frequency of ECE in the
      Surveillance, Epidemiology, and End Results (SEER) registry database,
      particularly as it related to nodal size. Our objective was to compare these
      findings with the literature. RESULTS: SEER data suggest that the likelihood of
      ECE does not increase linearly with LN size, whereas most reports in the
      literature suggest that the likelihood of ECE does increase with increasing LN
      size. CONCLUSIONS: SEER data and the literature are not consistent in describing
      the relationship between ECE and LN size. These results suggest the need for
      better standardization in the assessment and reporting of ECE.

PMID- 20824810
TI  - Aggressive variants of papillary thyroid carcinoma.
AB  - A number of histologic variants of well-differentiated papillary carcinoma have
      been found to be associated with more aggressive tumor behavior. Tall cell,
      columnar cell, diffuse sclerosing, solid/trabecular, and insular variants of well
      differentiated papillary thyroid cancer are all potentially more aggressive than
      conventional papillary thyroid cancer. When subjected to multivariate analysis,
      however, evidence that the histologic subtype of tumor is an independent
      predictor of outcome is weak. Rather, the aggressive variants tend to present
      with features recognized by other staging systems as associated with a worse
      prognosis, including higher histologic grade, extracapsular spread, large tumor
      size, and the presence of distant metastases. Prognosis is directly related to
      the presence of these features. The state of our knowledge is limited by the
      relatively small number of cases that have been studied. The presence of an
      aggressive variant of papillary carcinoma should alert the surgeon that he is
      dealing with a potentially aggressive tumor. Clinical treatment decisions should
      be based on the stage of the disease, influenced by the knowledge that the
      aggressive variants tend to be associated with higher risk factors. The surgeon
      must be prepared to perform at the first, or second stage, a total thyroidectomy,
      central compartment neck dissection, additional lymphadenectomy, and/or resection
      of invaded surrounding structures, and search for distant metastasis.
      Postoperative radioactive iodine should generally be administered for these
      variants as they will generally be intermediate to advanced tumors. The tall cell
      variant is often refractory to such treatment but may be susceptible to treatment
      targeted against BRAF mutation. External beam irradiation may be used in cases of
      incomplete resection.

PMID- 20824809
TI  - Postsurgical thyroid remnant estimation by (99m) Tc-pertechnetate scintigraphy
      predicts radioiodine ablation effectiveness in patients with differentiated
      thyroid carcinoma.
AB  - BACKGROUND: The purpose of this study was to evaluate the relationship between
      postsurgical neck (99m) technetium ((99m) Tc)-pertechnetate uptake and the rate
      of successful remnant ablation after radioiodine treatment in patients with
      differentiated thyroid carcinoma (DTC). METHODS: Retrospectively enrolled were
      232 patients with DTC who underwent total thyroidectomy and fixed activity
      ablation with 3.7 GBq 131I. The (99m) Tc scans were performed on all patients
      before 131I administration. Thyroid ablation was assessed after 6 to 12 months by
      thyroid-stimulating hormone (TSH)-stimulated 131I-WBS and thyroglobulin
      measurement. The rate of successful ablation, occurrence of radioiodine-induced
      thyroiditis, and length of hospitalization were correlated with the (99m) Tc
      pertechnetate scintigraphy results. RESULTS: A (99m) Tc uptake was significantly
      lower in ablated versus nonablated patients (p < .001). High (99m) Tc
      pertechnetate uptake, especially greater than 1.4%, predicted a high-risk of
      unsuccessful ablation. Higher (99m) Tc-pertechnetate uptake was also related to
      prolonged hospitalization and the occurrence of radioiodine-induced thyroiditis.
      CONCLUSION: The (99m) Tc-pertechnetate scintigraphy is a simple and feasible tool
      to evaluate thyroid remnants and to predict radioiodine ablation results in
      patients with DTC.

PMID- 20824811
TI  - Survey of orbital tumors at a comprehensive cancer center in the United States.
AB  - BACKGROUND: The purpose of this study was to evaluate the frequencies of various
      types of orbital lesions seen at a comprehensive cancer center in the United
      States. METHODS: In this retrospective case series, we reviewed the medical
      records of 268 consecutive patients referred to our orbital oncology service for
      evaluation of an orbital mass between November 1998 and February 2009. Each
      orbital lesion was documented by CT and/or MRI, and in most cases diagnosis was
      established with a tissue biopsy. Patients who were seen for second opinions and
      had inadequate follow-up data were excluded, as were patients with thyroid eye
      disease or orbital hemorrhage. RESULTS: The study included 134 men and 134 women
      aged 1 to 89 years at diagnosis (median, 55 years). Follow-up ranged from 0.06 to
      192 months (median, 15 months). Of the tumors, 171 (64%) were primary orbital, 69
      (26%) were secondary orbital, and 28 (10%) were metastatic tumors. Lesion types
      were as follows: secondary orbital tumors, 69 (26%); lymphoproliferative lesions,
      68 (25%); metastases, 28 (10%); epithelial lacrimal gland tumors, 27 (10%);
      inflammatory conditions, 21 (8%); vascular lesions, 20 (7%); mesenchymal tumors,
      18 (7%); optic nerve and nerve sheath tumors, 7 (3%); peripheral nerve tumors, 3
      (1%); histiocytic lesions, 3 (1%); cystic lesions, 3 (1%); and other lesions, 1
      (<1%). The most common histopathologic diagnoses were lymphoma, 50 cases (19%);
      orbital extension of sinus tumor, 25 (9%); lacrimal gland adenoid cystic
      carcinoma, 18 (7%); cavernous hemangioma, 15 (6%); orbital extension of brain
      tumor, 14 (5%); idiopathic orbital inflammation, 14 (5%); plasmacytoma, 8 (3%);
      reactive lymphoid hyperplasia, 7 (3%); metastatic breast cancer, 7 (3%); orbital
      extension of ocular adnexal basal cell carcinoma, 7 (3%); orbital extension of
      ocular adnexal melanoma, 6 (2%), rhabdomyosarcoma, 6 (2%); metastatic
      gastrointestinal cancer, 5 (2%); sarcoidosis, 5 (2%); and other less common
      lesions. Forty-two lesions (16%) were intraconal, and 226 (84%) were extraconal.
      There were 169 (63%) malignant tumors and 99 (37%) were benign tumors. The rate
      of malignant lesions was 65% in children and 63% in adults (>=18 years).
      Malignant conditions encountered at a higher rate than previously reported
      included lymphoma (19% vs 8% to 13%), secondary orbital tumors (26% vs 13% to
      20%), orbital metastases (10% vs 2% to 7%), and malignant epithelial lacrimal
      gland tumors (9% vs 2% to 3%). CONCLUSION: Our findings highlight the distinctive
      nature of the orbital oncology experience at a comprehensive cancer center. We
      found higher than previously reported rates of malignant tumors (63% of all
      tumors), particularly secondary tumors, malignant epithelial lacrimal gland
      tumors, and orbital metastases.

PMID- 20824812
TI  - DMBT1 is a novel gene induced by IL-22 in ulcerative colitis.
AB  - BACKGROUND: Interleukin (IL)-22 is a recently identified cytokine that is
      suggested to play pivotal roles in various inflammatory diseases. Although the IL
      22 receptor 1 (IL-22R1) is restrictively expressed in epithelial cells in the
      colon, the role of IL-22 in colonic diseases still remains unclear. In this study
      microarray analyses revealed that deleted in malignant brain tumors 1 (DMBT1) is
      a novel upregulated gene in IL-22-stimulated colon cancer cells. Therefore, we
      investigated the involvement of DMBT1 and IL-22 in ulcerative colitis (UC)
      tissues and examined the mechanism regulating the expression of DMBT1 in response
      to IL-22 stimulation. METHODS: Changes of gene expression in IL-22-stimulated
      SW403 cells were investigated by microarray analyses. The effects of IL-22 on
      DMBT1 expression were examined in SW403 cells using a small interfering RNA
      (si)RNA for STAT3 or inhibitors for MEK, PI3K, and nuclear factor kappa B (NF
      kappaB). The element responsible for IL-22-induced DMBT1 promoter activation was
      determined by a promoter deletion and electrophoretic mobility shift assay
      (EMSA). Expression of IL-22, IL-22R1, and DMBT1 in UC tissues was analyzed by
      real-time reverse-transcription polymerase chain reaction (RT-PCR) and
      immunohistochemistry. RESULTS: IL-22 treatment enhanced the expression of DMBT1
      through STAT3 tyrosine phosphorylation and NF-kappaB activation in colon cancer
      cells. The IL-22-responsive element was located between -187 and -179 in the
      DMBT1 promoter region. In the UC mucosa the levels of DMBT1 and IL-22 mRNA
      expression were significantly enhanced and positively correlated, the numbers of
      IL-22-positive lymphocytes were increased, and the expression of IL-22R1 and
      DMBT1 was enhanced in the inflamed epithelium. CONCLUSIONS: The IL-22/DMBT1 axis
      may play a pivotal role in the pathophysiology of UC.

PMID- 20824813
TI  - Bones in pediatric Crohn's disease: a review of fracture risk in children and
      adults.
AB  - There is evidence to suggest that the inflammation associated with Crohn's
      disease (CD) impacts the bone health of patients, predisposing them to early
      onset osteoporosis and increasing their risk of fracture. Fractures have been
      documented in patients with CD, with a high proportion of these being found
      during young adulthood, which suggests that these patients are not simply
      fracturing as a result of the normal aging process but rather due to the presence
      of CD. In population terms, patients with CD have increased risk of fracture
      compared with the general population. Studies in children suggest that,
      irrespective of time on corticosteroid therapy, the underlying systemic
      inflammation associated with CD is an independent detrimental influence on the
      bone health of children with CD. This poses the question as to whether the onset
      of disease in childhood predisposes the individual to increased risk of future
      fractures later in life, as a result of decreased peak bone mass during the
      growing years. It is generally believed that dual energy x-ray absorptiometry
      assessed areal bone mineral density is a good indicator of fracture risk;
      however, several studies have shown this may not be the case. New research,
      utilizing peripheral quantitative computed tomography, which provides a true
      volumetric assessment of bone, suggests altered bone geometry in patients with
      CD, which poses a structural threat by being more brittle and susceptible to
      damage accumulation.

PMID- 20824814
TI  - Neonatal exposure to fecal antigens reduces intestinal inflammation.
AB  - BACKGROUND: A role for bacterial antigens in the pathogenesis of inflammatory
      bowel disease (IBD) has been established in enhanced humoral and cellular immune
      response to ubiquitous antigens of the enteric flora. However, we have recently
      shown that bacterial antigens in the absence of live bacteria cannot initiate an
      intestinal inflammation in IBD-prone interleukin (IL)-10 gene-deficient mice. The
      objective was to investigate whether neonatal exposure to antigens of their own
      endogenous flora can tolerize mice to bacterial antigens. METHODS: IL-10 gene
      deficient neonates were injected intraperitoneally within 72 hours of birth with
      a sterile solution of bacterial lysates prepared from fecal material of either
      conventionally raised mice (contains bacterial antigens) or axenic mice (lacks
      bacterial antigens). The onset of intestinal inflammation was monitored as the
      appearance of occult blood in the stool in weekly hemoccult analysis. Mice were
      sacrificed between age 15 and 19 weeks and tested for histopathologic injury,
      intestinal inflammation, and systemic response to bacterial antigens. RESULTS: In
      mice neonatally exposed to bacterial antigens the onset of intestinal
      inflammation was delayed and the incidence of histopathologic injury at age 18
      weeks was reduced. In addition, mice injected with lysates from conventionally
      raised mice exhibited decreased release of proinflammatory cytokines (interferon
      gamma [IFN-gamma] and IL-17) in intestinal tissue and demonstrated reduced
      bacteria-stimulated systemic responses when compared to mice injected with
      lysates derived from bacteria-free, axenic mice. CONCLUSIONS: Neonatal
      intraperitoneal injection of antigens from the commensal flora causes long
      lasting changes in systemic and mucosal immune responses resulting in delayed
      onset of intestinal inflammation and injury in IBD-prone IL-10 gene-deficient
      mice.

PMID- 20824815
TI  - Misclassification of dysplasia in patients with inflammatory bowel disease:
      consequences for progression rates to advanced neoplasia.
AB  - BACKGROUND: The natural behavior of flat low-grade (LGD) and indefinite dysplasia
      (IND) in patients with inflammatory bowel disease (IBD) remains uncertain and
      seems to be dependent on the interpretation of the pathologist. We studied the
      progression rate of flat LGD and IND to advanced neoplasia (high-grade dysplasia
      [HGD] or colorectal cancer [CRC]) before and after histopathological review by a
      panel of gastrointestinal expert pathologists. METHODS: A nationwide pathology
      database was used to identify IBD patients with dysplasia in six Dutch university
      medical centers between 1990 and 2006. Medical charts of patients with recorded
      flat LGD or IND were reviewed. Histological slides from three university medical
      centers were reviewed by a panel of three expert gastrointestinal pathologists.
      RESULTS: We identified 113 flat LGD patients and 26 flat IND patients. Advanced
      neoplasia was found in 18 flat LGD patients (16%) after a median follow-up of 48
      months, resulting in a 5-year progression rate of 12%. Five IND patients (19%)
      developed advanced neoplasia after a median follow-up of 24 months, resulting in
      a 5-year progression rate of 21%. Review of 1547 histological slides from 87
      patients resulted in an increase of the 5-year progression rate of flat LGD to
      advanced neoplasia to 37%, whereas the progression rate of IND decreased to 5%.
      CONCLUSIONS: A diagnosis of flat LGD that is confirmed by a panel of expert
      gastrointestinal pathologists is associated with a substantial risk of
      progression to advanced neoplasia, while confirmed IND is associated with a low
      risk of progression.

PMID- 20824816
TI  - Severe neutropenia following infliximab treatment in a child with ulcerative
      colitis.

PMID- 20824817
TI  - Functional analysis of agalactosyl IgG in inflammatory bowel disease patients.
AB  - BACKGROUND: Agalactosyl immunoglobulin (Ig) G is increased in inflammatory bowel
      disease (IBD) similarly to rheumatoid arthritis (RA). The lectin complement
      pathway is shown to be activated through association of agalactosyl IgG with
      mannan-binding lectin (MBL) in RA. Functional changes of IgG agalactosylation in
      IBD, however, have not yet been clarified. METHODS: The ratio of the
      agalactosyl/non-agalactosyl fraction in fucosylated IgG oligosaccharides
      (G0F/G2F) and serum MBL levels were analyzed in 59 patients with Crohn's disease
      (CD), 64 ulcerative colitis (UC), and 39 healthy volunteers (HV). The MBL levels
      associated with serum IgG were analyzed by enzyme-linked immunosorbent assay. MBL
      expression in the intestinal mucosa was analyzed by immunohistochemistry.
      Phagocytosis of sheep red blood cells (SRBC) reacted with either an agalactosyl
      or non-agalactosyl SRBC-specific IgG antibody was determined by flow cytometry.
      RESULTS: The serum MBL levels were not significantly different among CD, UC, or
      HV. In patients with CD, the serum MBL levels were negatively correlated with the
      Crohn's Disease Activity Index (CDAI). The levels of MBL associated with
      agalactosyl IgG were not different from those associated with non-agalactosyl
      IgG. Immunoreactivity to MBL was less in the inflamed mucosa compared with the
      noninflamed mucosa. Phagocytic activity of SRBC was significantly higher in the
      presence of agalactosyl IgG compared to non-agalactosyl IgG. CONCLUSIONS:
      Agalactosyl IgG oligosaccharides enhanced antibody-dependent phagocytosis in
      vitro but did not activate the lectin complement pathway. Oligosaccharide
      alterations of IgG are not only a marker of IBD but also functionally modulate
      the immune function of IBD.

PMID- 20824818
TI  - Temporal trends in disease outcomes related to Clostridium difficile infection in
      patients with inflammatory bowel disease.
AB  - BACKGROUND: Clostridium difficile has emerged as an important pathogen in
      patients with inflammatory bowel disease (IBD) and is associated with increased
      morbidity and mortality. No studies have examined the temporal change in severity
      of C. difficile infection (CDI) complicating IBD. METHODS: Using data from the
      Nationwide Inpatient Sample, we identified all IBD-related hospitalizations
      during the years 1998, 2004, and 2007 and examined hospitalizations with a
      coexisting diagnosis of C. difficile. We compared the absolute outcomes of in
      hospital mortality and colectomy in the C. difficile-IBD cohort during these
      timepoints, and also examined these outcomes relative to non-C. difficile IBD
      controls during each corresponding year. RESULTS: During 1998, 2004, and 2007,
      approximately 1.4%, 2.3%, and 2.9% of all IBD hospitalizations nationwide were
      complicated by CDI (P < 0.001). The absolute mortality in the C. difficile-IBD
      cohort increased from 5.9%-7.2% (P = 0.052) with a nonsignificant increase in
      colectomy rate from 3.8%-4.5% between 1998 and 2007. Compared to non-C. difficile
      IBD controls, there was an increase in the relative mortality risk associated
      with C. difficile from 1998 (odds ratio [OR] 2.38, 95% confidence interval [CI]:
      1.52-3.72) to 2007 (OR 3.38, 95% CI: 2.66-4.29) (P = 0.15) with a significant
      increase in total colectomy odds from 1998 (OR 1.39, 95% CI: 0.81-2.37) to 2007
      (OR 2.51, 95% CI: 1.90-3.34) (P = 0.03). CONCLUSION: There has been a temporal
      increase nationwide in CDI complicating IBD hospitalizations. The excess
      morbidity associated with C. difficile infection in hospitalized IBD patients has
      increased between 1998 and 2007.

PMID- 20824819
TI  - Smoking status and response to thiopurines in steroid-dependent inflammatory
      bowel disease.
AB  - BACKGROUND: The influence of smoking on inflammatory bowel disease (IBD)
      susceptibility and on its clinical course is well known, but not its impact on
      drug efficacy. The aim of this study was to evaluate the response to thiopurines
      in patients with steroid-dependent IBD according to their smoking habits.
      METHODS: The medical records of 163 IBD patients (103 Crohn's disease [CD], 60
      ulcerative colitis [UC]) in whom thiopurines were started because of steroid
      dependency were reviewed. Therapeutic response was defined by steroid-free
      clinical remission for at least 6 months after 12 months of starting thiopurines.
      Clinical data and smoking status at diagnosis, at the time thiopurines were
      started, and during the follow-up were registered. RESULTS: A therapeutic
      response was obtained in 72% of CD and 61% of UC patients. Smoking habits did not
      influence the rate of response to thiopurines, the need for rescue therapies, or
      the development of penetrating/stricturing complications (CD) or proximal
      progression (UC). However, CD responders who continued smoking required new
      courses of steroids more often during follow-up. No influence of smoking was
      found when these outcomes were analyzed depending on gender or disease location.
      In the multivariate analysis, smoking status was the only predictive factor of
      drug tolerance. CONCLUSIONS: Active smoking does not influence the response to
      thiopurines in steroid-dependent IBD, but may decrease the likelihood of drug
      tolerance.

PMID- 20824820
TI  - cDNA cloning and induction of tyrosine hydroxylase gene from the diamondback
      moth, Plutella xylostella.
AB  - We cloned a full-length tyrosine hydroxylase cDNA from the integument of the
      diamondback moth, Plutella xylostella. In the phylogenetic tree, tyrosine
      hydroxylase (PxTH) clustered with the other lepidopteran THs. Serine residues in
      the PxTH sequence, namely Ser(24), Ser(31), Ser(35), Ser(53), and Ser(65), were
      predicted to be the target sites for phosphorylation based on PROSITE analysis.
      In particular, Ser(35) of PxTH is highly conserved across a broad phylogenetic
      range of animal taxa including rat and human. Western blot analysis using both
      PxTH-Ab1 and PxTH-Ab2 polyclonal antibodies verified the expression of PxTH in
      all life cycle stages of P. xylostella, namely the larval, pupal, and adult
      stages. To examine the possible immune function of PxTH in P. xylostella, PxTH
      gene expression was investigated by RT-PCR and western blotting analysis after
      challenging P. xylostella with bacteria. PxTH expression was elevated 1 h post
      infection and was continued till 12 h of post-infection relative to control
      larvae injected with sterile water.

PMID- 20824821
TI  - Characterization of the Mamestra configurata (Lepidoptera: Noctuidae) larval
      midgut protease complement and adaptation to feeding on artificial diet, Brassica
      species, and protease inhibitor.
AB  - The midgut protease profiles from 5th instar Mamestra configurata larvae fed
      various diets (standard artificial diet, low protein diet, low protein diet with
      soybean trypsin inhibitor [SBTI], or Brassica napus) were characterized by one
      dimensional enzymography in gelatin gels. The gut protease profile of larvae fed
      B. napus possessed protease activities of molecular masses of approximately 33
      and 55 kDa, which were not present in the guts of larvae fed artificial diet.
      Similarly, larvae fed artificial diet had protease activities of molecular masses
      of approximately 21, 30, and 100 kDa that were absent in larvae fed B. napus.
      Protease profiles changed within 12 to 24 h after switching larvae from
      artificial diet to plant diet and vice versa. The gut protease profiles from
      larvae fed various other brassicaceous species and lines having different
      secondary metabolite profiles did not differ despite significant differences in
      larval growth rates on the different host plants. Genes encoding putative
      digestive proteolytic enzymes, including four carboxypeptidases, five
      aminopeptidases, and 48 serine proteases, were identified in cDNA libraries from
      4th instar M. configurata midgut tissue. Many of the protease-encoding genes were
      expressed at similar levels on all diets; however, three chymoptrypsin-like genes
      (McSP23, McSP27, and McSP37) were expressed at much higher levels on standard
      artificial diet and diet containing SBTI as was the trypsin-like gene McSP34. The
      expression of the trypsin-like gene McSP50 was highest on B. napus. The
      adaptation of M. configurata digestive biochemistry to different diets is
      discussed in the context of the flexibility of polyphagous insects to changing
      diet sources.

PMID- 20824822
TI  - Putative-farnesoic acid O-methyltransferase (FAMeT) in medfly reproduction.
AB  - A gene potentially involved in juvenile hormone (JH) biosynthesis was previously
      identified in Ceratitis capitata as the putative-farnesoic acid O
      methyltransferase (FAMeT). Since JH is involved in insect reproduction, we
      silenced the putative-FAMeT expression by RNA interference in Ceratitis capitata
      to evaluate its implication in egg production. FAMeT gene expression was knocked
      down in females and males after eclosion and in 1- and 2-day-old females. Treated
      specimens were left to mate with each other or with untreated partners to
      evaluate the extent of each sex influencing egg production. Gene silencing was
      investigated by Real-Time PCR. Results unambiguously showed that FAMeT has a
      measurable role on the fertility of both medfly sexes.

PMID- 20824823
TI  - Comparative studies of acetylcholinesterase purified from three field populations
      of Liposcelis entomophila (enderlein) (psocoptera: liposcelididae).
AB  - Acetylcholinesterace (AChE) is known to be the major target for organophophate
      and carbamate insecticides and biomolecular changes to AChE have been
      demonstrated to be an important mechanism for insecticide resistance in many
      insect species. In this study, AChE from three field populations of Liposcelis
      entomophila (Enderlein) (Psocoptera: Liposcelididae) was purified by affinity
      chromatography and subsequently characterized by its Michaelis-Menten kinetics to
      determine if detectable changes to AChE have occurred. Bioassays revealed that
      the potential resistance threat of psocids in Sichuan Province (GH) was greater
      than either Hubei Province (WH) or Chongqing Municipality (BB). Compared to the
      other two populations, the WH population possessed the highest specific activity
      of purified AChE. Kinetic analyses indicated that the purified AChE from GH
      population expressed a significantly lower affinity to the substrate and a higher
      catalytic activity toward acetylthiocholine iodide (ATChI) (i.e., higher K(m) and
      V(max) values) than BB and WH populations. In vitro studies of AChE suggest that
      five inhibitors (aldicarb, eserine, BW284C51, omethoate, and propoxur) all
      possess strong inhibitory effects with eserine having the strongest inhibitory
      effect against purified AChE. According to bimolecular rate constants (k(i)), the
      purified AChE from GH population was least sensitive to all inhibitors except for
      omethoate. The differences in AChE among the three populations may be partially
      attributed to the differences in pesticide application and control practices for
      psocids among the three locations.

PMID- 20824824
TI  - Alternative versus conventional institutional settings for birth.
AB  - BACKGROUND: Alternative institutional settings have been established for the care
      of pregnant women who prefer and require little or no medical intervention. The
      settings may offer care throughout pregnancy and birth, or only during labour;
      they may be part of hospitals or freestanding entities. Specially designed labour
      rooms include bedroom-like rooms, ambient rooms, and Snoezelen rooms. OBJECTIVES:
      Primary: to assess the effects of care in an alternative institutional birth
      environment compared to care in a conventional institutional setting. Secondary:
      to determine if the effects of birth settings are influenced by staffing,
      architectural features, organizational models or geographical location. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (31 May 2010). SELECTION CRITERIA: All randomized or quasi-randomized
      controlled trials which compared the effects of an alternative institutional
      maternity care setting to conventional hospital care. DATA COLLECTION AND
      ANALYSIS: We used standard methods of the Cochrane Collaboration Pregnancy and
      Childbirth Group. Two review authors evaluated methodological quality. We
      performed double data entry and have presented results using risk ratios (RR) and
      95% confidence intervals (CI). MAIN RESULTS: Nine trials involving 10684 women
      met the inclusion criteria. We found no trials of freestanding birth centres or
      Snoezelen rooms. Allocation to an alternative setting increased the likelihood
      of: no intrapartum analgesia/anaesthesia (five trials, n = 7842; RR 1.17, 95% CI
      1.01 to 1.35); spontaneous vaginal birth (eight trials; n = 10,218; RR 1.04, 95%
      CI 1.02 to 1.06); breastfeeding at six to eight weeks (one trial, n = 1147; RR
      1.04, 95% CI 1.02 to 1.06); and very positive views of care (two trials, n =
      1207; RR 1.96, 95% CI 1.78 to 2.15). Allocation to an alternative setting
      decreased the likelihood of epidural analgesia (seven trials, n = 9820; RR 0.82,
      95% CI 0.75 to 0.89); oxytocin augmentation of labour (seven trials, n = 10,020;
      RR 0.78, 95% CI 0.66 to 0.91); and episiotomy (seven trials, n = 9944; RR 0.83,
      95% CI 0.77 to 0.90). There was no apparent effect on serious perinatal or
      maternal morbidity/mortality, other adverse neonatal outcomes, or postpartum
      hemorrhage. No firm conclusions could be drawn regarding the effects of
      variations in staffing, organizational models, or architectural characteristics
      of the alternative settings. AUTHORS' CONCLUSIONS: When compared to conventional
      settings, hospital-based alternative birth settings are associated with increased
      likelihood of spontaneous vaginal birth, reduced medical interventions and
      increased maternal satisfaction.

PMID- 20824825
TI  - Gamma and other cephalocondylic intramedullary nails versus extramedullary
      implants for extracapsular hip fractures in adults.
AB  - BACKGROUND: Two types of implants used for the surgical fixation of extracapsular
      hip fractures are cephalocondylic intramedullary nails, which are inserted into
      the femoral canal proximally to distally across the fracture, and extramedullary
      implants (e.g. the sliding hip screw). OBJECTIVES: To compare cephalocondylic
      intramedullary nails with extramedullary implants for extracapsular hip fractures
      in adults. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle
      Trauma Group Specialised Register (April 2010), The Cochrane Central Register of
      Controlled Trials (The Cochrane Library 2010, Issue 1), MEDLINE (1950 to March
      2010), EMBASE (1980 to 2010 Week 13), and other sources. SELECTION CRITERIA: All
      randomised and quasi-randomised controlled trials comparing cephalocondylic nails
      with extramedullary implants for extracapsular hip fractures. DATA COLLECTION AND
      ANALYSIS: Both authors independently assessed trial quality and extracted data.
      Wherever appropriate, results were pooled. MAIN RESULTS: We included 43 trials
      containing predominantly older people with mainly trochanteric fractures. Twenty
      two trials (3749 participants) compared the Gamma nail with the sliding hip screw
      (SHS). The Gamma nail was associated with increased risk of operative and later
      fracture of the femur and increased reoperation rate. There were no major
      differences between implants in wound infection, mortality or medical
      complications.Five trials (623 participants) compared the intramedullary hip
      screw (IMHS) with the SHS. Fracture fixation complications were more common in
      the IMHS group. Results for post-operative complications, mortality and
      functional outcomes were similar in both groups.Three trials (394 participants)
      showed no difference in fracture fixation complications, reoperation, wound
      infection and length of hospital stay for proximal femoral nail (PFN) versus the
      SHS.None of the 10 trials (1491 participants) of other nail versus extramedullary
      implant comparisons for trochanteric fractures provided sufficient evidence to
      establish definite differences between the implants under test.Two trials (65
      participants) found intramedullary nails were associated with fewer fracture
      fixation complications than fixed nail plates for unstable fractures at the level
      of the lesser trochanter.Two trials (124 participants) found a tendency to less
      fracture healing complications with the intramedullary nails compared with fixed
      nail plates for subtrochanteric fractures. AUTHORS' CONCLUSIONS: With its lower
      complication rate in comparison with intramedullary nails, and absence of
      functional outcome data to the contrary, the SHS appears superior for
      trochanteric fractures. Further studies are required to confirm whether more
      recently developed designs of intramedullary nail avoid the complications of
      previous nails. Intramedullary nails may have advantages over fixed angle plates
      for subtrochanteric and some unstable trochanteric fractures, but further studies
      are required.

PMID- 20824826
TI  - WITHDRAWN: Interventions for nausea and vomiting in early pregnancy.
AB  - BACKGROUND: Nausea and vomiting are the most common symptoms experienced in early
      pregnancy, with nausea affecting between 70 and 85% of women. About half of
      pregnant women experience vomiting. OBJECTIVES: To assess the effects of
      different methods of treating nausea and vomiting in early pregnancy. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register
      (December 2002) and the Cochrane Central Register of Controlled Trials (The
      Cochrane Library, Issue 4, 2002). SELECTION CRITERIA: Randomised trials of any
      treatment for nausea and/or vomiting in early pregnancy. DATA COLLECTION AND
      ANALYSIS: Two reviewers assessed the trial quality and extracted the data
      independently. MAIN RESULTS: Twenty-eight trials met the inclusion criteria. For
      milder degrees of nausea and vomiting, 21 trials were included. These trials were
      of variable quality. Nausea treatments were: different antihistamine medications,
      vitamin B6 (pyridoxine), the combination tablet Debendox (Bendectin), P6
      acupressure and ginger. For hyperemesis gravidarum, seven trials were identified
      testing treatments with oral ginger root extract, oral or injected
      corticosteroids or injected adrenocorticotropic hormone (ACTH), intravenous
      diazepam and acupuncture. Based on 12 trials, there was an overall reduction in
      nausea from anti-emetic medication (odds ratio 0.16, 95% confidence interval 0.08
      to 0.33). AUTHORS' CONCLUSIONS: Anti-emetic medication appears to reduce the
      frequency of nausea in early pregnancy. There is some evidence of adverse
      effects, but there is very little information on effects on fetal outcomes from
      randomised controlled trials. Of newer treatments, pyridoxine (vitamin B6)
      appears to be more effective in reducing the severity of nausea. The results from
      trials of P6 acupressure are equivocal. No trials of treatments for hyperemesis
      gravidarum show any evidence of benefit. Evidence from observational studies
      suggests no evidence of teratogenicity from any of these treatments.

PMID- 20824827
TI  - Short-course antibiotics for acute otitis media.
AB  - BACKGROUND: Acute otitis media (AOM) is a common illness during childhood, for
      which antibiotics are frequently prescribed. OBJECTIVES: To determine the
      effectiveness of a short course of antibiotics (less than seven days) in
      comparison to a long course of antibiotics (seven days or greater) for the
      treatment of AOM in children. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 4)
      which contains the Acute Respiratory Infections Group's Specialised Register,
      MEDLINE, EMBASE, MEDLINE In-Process & Other Non-Indexed Citations, CINAHL, BIOSIS
      Previews, OCLC Papers First and Proceedings First, Proquest Dissertations and
      Theses (inception to November 2009); International Pharmaceutical Abstracts, the
      NLM Gateway, ClinicalTrials.gov and Current Controlled Trials (inception to
      August 2008). SELECTION CRITERIA: Trials were included if they met the following
      criteria: participants aged one month to 18 years; clinical diagnosis of ear
      infection; no previous antimicrobial therapy; and randomisation to treatment with
      less than seven days versus seven days or more of antibiotics. DATA COLLECTION
      AND ANALYSIS: The primary outcome of treatment failure was defined as the absence
      of clinical resolution, relapse or recurrence of AOM during one month following
      initiation of therapy. Treatment outcomes were extracted from individual studies
      and combined in the form of a summary odds ratio (OR). A summary OR of 1.0
      indicates that the treatment failure rate following less than seven days of
      antibiotic treatment was similar to the failure rate following seven days or more
      of treatment. MAIN RESULTS: This update included 49 trials containing 12,045
      participants. Risk of treatment failure was higher with short courses of
      antibiotics (OR 1.34, 95% CI 1.15 to 1.55) at one month after initiation of
      therapy (21% failure with short-course treatment and 18% with long-course;
      absolute difference of 3% between groups). There were no differences found when
      examining treatment with ceftriaxone for less than seven days (30% failure in
      those receiving ceftriaxone and 27% in short-acting antibiotics administered for
      seven days or more) or azithromycin for less than seven days (18% failure in both
      those receiving azithromycin and short-acting antibiotics administered for seven
      days or more) with respect to risk of treatment failure at one month or less.
      Significant reductions in gastrointestinal adverse events were observed for
      treatment with short-acting antibiotics and azithromycin. AUTHORS' CONCLUSIONS:
      Clinicians need to evaluate whether the minimal short-term benefit from longer
      treatment of antibiotics is worth exposing children to a longer course of
      antibiotics.

PMID- 20824828
TI  - Fixed dose subcutaneous low molecular weight heparins versus adjusted dose
      unfractionated heparin for venous thromboembolism.
AB  - BACKGROUND: Low molecular weight heparins (LMWHs) have been shown to be effective
      and safe in preventing venous thromboembolism (VTE). They may also be effective
      for the initial treatment of VTE. This is an update of a Cochrane review first
      published in 1999 and previously updated in 2004. OBJECTIVES: To determine the
      effect of LMWH compared with unfractionated heparin (UFH) for the initial
      treatment of VTE. SEARCH STRATEGY: Trials were identified by searching the
      Cochrane Peripheral Vascular Diseases Group Specialised Register and CENTRAL (The
      Cochrane Library). Colleagues and pharmaceutical companies were contacted for
      additional information. SELECTION CRITERIA: Randomised controlled trials
      comparing fixed dose subcutaneous LMWH with adjusted dose intravenous or
      subcutaneous UFH in people with VTE. DATA COLLECTION AND ANALYSIS: Two review
      authors assessed trials for inclusion and quality, and extracted data
      independently. MAIN RESULTS: Twenty-three studies were included (n = 9587).
      Thrombotic complications occurred in 3.6% of participants treated with LMWH
      compared with 5.3% treated with UFH (odds ratio (OR) 0.70; 95% confidence
      interval (CI) 0.57 to 0.85). Thrombus size was reduced in 53% of participants
      treated with LMWH and 45% treated with UFH (OR 0.69; 95% CI 0.59 to 0.81). Major
      haemorrhages occurred in 1.1% of participants treated with LMWH compared with
      1.9% treated with UFH (OR 0.58; 95% CI 0.40 to 0.83). In 19 trials, 4.3% of
      participants treated with LMWH died compared with 5.8% of participants treated
      with UFH (OR 0.77; 95% CI 0.63 to 0.93).Nine studies (n = 4451) examined proximal
      thrombosis, 2192 participants were treated with LMWH and 2259 with UFH. Subgroup
      analysis showed statistically significant reductions favouring LMWH in thrombotic
      complications and major haemorrhage. By end of follow up, 80 (3.6%) participants
      treated with LMWH had thrombotic complications compared with 143 (6.3%) treated
      with UFH (OR 0.57; 95% CI 0.44 to 0.75). Major haemorrhages occurred in 18 (1.0%)
      participants treated with LMWH compared with 37 (2.1%) treated with UFH (OR 0.50;
      95% CI 0.29 to 0.85). Nine studies showed a statistically significant reduction
      in mortality favouring LMWH. By the end of follow up, 3.3% (70/2094) of
      participants treated with LMWH had died and 5.3% (110/2063) treated with UFH.
      AUTHORS' CONCLUSIONS: Fixed dose LMWH is more effective and safer than adjusted
      dose UFH for the initial treatment of VTE. Compared to UFH, LMWH significantly
      reduced the incidence of thrombotic complications, the occurrence of major
      haemorrhage during initial treatment and overall mortality at follow up.

PMID- 20824829
TI  - Surgery for faecal incontinence in adults.
AB  - BACKGROUND: Faecal incontinence is a debilitating problem with significant
      medical, social and economic implications. Treatment options include
      conservative, non-operative interventions (e.g. pelvic floor muscle training,
      biofeedback, drugs) and surgical procedures. A surgical procedure may be aimed at
      correcting an obvious mechanical defect, or augmenting a functionally deficient
      but structurally intact sphincter complex. OBJECTIVES: To assess the effects of
      surgical techniques for the treatment of faecal incontinence in adults who do not
      have rectal prolapse. Our aim was firstly to compare surgical management with non
      surgical management and secondly, to compare the various surgical techniques.
      SEARCH STRATEGY: Electronic searches of the Cochrane Incontinence Group
      Specialised Register (searched 26 November 2009), the Cochrane Colorectal Cancer
      Group Specialised Register (searched 26 November 2009), CENTRAL (The Cochrane
      Library 2009) and EMBASE (1 January 1998 to 30 June 2009) were undertaken. The
      British Journal of Surgery (1 January 1995 to 30 June 2009) Colorectal Diseases
      (1 January 2000 to 30 June 2009) and the Diseases of the Colon and Rectum (1
      January 1995 to 30 June 2009) were specifically handsearched. The proceedings of
      the UK Association of Coloproctology meeting held from 1999 to 2009 were perused.
      Reference lists of all relevant articles were searched for further trials.
      SELECTION CRITERIA: All randomised or quasi-randomised trials of surgery in the
      management of adult faecal incontinence (other than surgery for rectal prolapse).
      DATA COLLECTION AND ANALYSIS: Three reviewers independently selected studies from
      the literature, assessed the methodological quality of eligible trials and
      extracted data. The three primary outcome measures were: change or deterioration
      in incontinence, failure to achieve full continence, and the presence of faecal
      urgency. MAIN RESULTS: Thirteen trials were included with a total sample size of
      440 participants. Two trials included a group managed non-surgically. One trial
      compared levator with anal plug electrostimulation and one compared artificial
      bowel sphincter with best supportive care. The artificial bowel sphincter
      resulted in significant improvements in at least one primary outcome but numbers
      were small. The other trial showed no difference in primary outcome
      measures.Eleven trials compared different surgical interventions. These included
      anterior levatorplasty versus postanal repair, anterior levatorplasty versus
      total pelvic floor repair, total pelvic floor versus postanal repair, end to end
      versus overlap sphincter repair, overlap repair with or without a defunctioning
      stoma or with or without biofeedback, injection of silicone, hydrogel,
      physiological saline, carbon beads or collagen bulking agents, total pelvic floor
      repair versus repair plus internal sphincter plication and neosphincter formation
      versus total pelvic floor repair. Sacral nerve stimulation and injectables are
      also considered in separate Cochrane reviews. Only one comparison had more than
      one trial (total pelvic floor versus postanal repair, 44 participants) and no
      trial showed any difference in primary outcome measures. AUTHORS' CONCLUSIONS:
      Despite more studies being included in this update, the continued small number of
      relevant trials identified together with their small sample sizes and other
      methodological weaknesses continue to limit the usefulness of this review for
      guiding practice. It was impossible to identify or refute clinically important
      differences between the alternative surgical procedures. Larger rigorous trials
      are still needed. However, it should be recognised that the optimal treatment
      regime may be a complex combination of various surgical and non-surgical
      therapies.

PMID- 20824830
TI  - Surgical procedures for evacuating incomplete miscarriage.
AB  - BACKGROUND: Incomplete miscarriage is a major problem that should be effectively
      managed with safe and appropriate procedures. Surgical evacuation of the uterus
      for management of incomplete miscarriage usually involves vacuum aspiration or
      sharp curettage. OBJECTIVES: To compare the safety and effectiveness of surgical
      uterine evacuation methods for management of incomplete miscarriage. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (July 2010). SELECTION CRITERIA: Randomized trials where different
      surgical methods were used to manage incomplete miscarriage were eligible for
      inclusion. DATA COLLECTION AND ANALYSIS: We extracted population characteristics,
      settings, and exclusion criteria, in addition to outcomes such as complications
      of the procedure, duration, need for re-evacuation, blood transfusion, and
      analgesia/anesthesia. MAIN RESULTS: Two trials (involving 550 women) were
      included. Vacuum aspiration was associated with statistically significantly
      decreased blood loss (mean difference (MD) -17.10 ml, 95% confidence interval
      (CI) -24.05 to -10.15 ml), less pain during the procedure (risk ratio (RR) 0.74,
      95% CI 0.61 to 0.90), and shorter duration of the procedure (MD -1.20 minutes,
      95% CI -1.53 to -0.87 minutes), than sharp metal curettage, in the single study
      that evaluated these outcomes in 357 women. Serious complications such as uterine
      perforation and other morbidity were rare and the sample sizes of the trials were
      not large enough to evaluate small or moderate differences. AUTHORS' CONCLUSIONS:
      Although the review indicates that vacuum aspiration is safe, quick to perform,
      and less painful than sharp curettage, and should be recommended for use in the
      management of incomplete miscarriage, the results are based on data from only one
      study. Analgesia and sedation should be provided as necessary for the procedure.

PMID- 20824831
TI  - Platelet glycoprotein IIb/IIIa blockers during percutaneous coronary intervention
      and as the initial medical treatment of non-ST segment elevation acute coronary
      syndromes.
AB  - BACKGROUND: During percutaneous coronary intervention (PCI), and in non-ST
      segment elevation acute coronary syndromes (NSTEACS), the risk of acute vessel
      occlusion by thrombosis is high. IIb/IIIa blockers strongly inhibit platelet
      aggregation and may prevent mortality and myocardial infarction (MI). This is an
      update of a Cochrane review first published in 2001, and previously updated in
      2007. OBJECTIVES: To assess the effects and safety of IIb/IIIa blockers when
      administered during PCI, and as initial medical treatment in patients with
      NSTEACS. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled
      Trials (CENTRAL) on The Cochrane Library (Issue 3, 2009), MEDLINE (1966 to
      October 2009), and EMBASE (1980 to October 2009). SELECTION CRITERIA: Randomised
      controlled trials comparing intravenous IIb/IIIa blockers with placebo or usual
      care. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies
      for inclusion, assessed trial quality and extracted data. We collected major
      bleeding as adverse effect information from the trials. Odds ratios (OR) and 95%
      confidence intervals (CI) were used for effect measures. MAIN RESULTS: Forty
      eight trials involving 62,417 patients were included. During PCI, IIb/IIIa
      blockers decreased mortality at 30 days (OR 0.76, 95% CI 0.62 to 0.95) and at six
      months (OR 0.84, 95% CI 0.71 to 1.00). Death or MI was decreased both at 30 days
      (OR 0.65, 95% CI 0.60 to 0.72), and at 6 months (OR 0.70, 95% CI 0.61 to 0.81),
      although severe bleeding was increased (OR 1.38, 95% CI 1.20 to 1.59; absolute
      risk increase (ARI) 8.0 per 1000). The efficacy results were homogeneous for
      every endpoint according to the clinical condition of the patients, but were less
      marked for patients pre-treated with clopidogrel, especially in patients without
      ACS.As initial medical treatment of NSTEACS, IIb/IIIa blockers did not decrease
      mortality at 30 days (OR 0.91, 95% CI 0.80 to 1.03) or at six months (OR 1.00,
      95% CI 0.87 to 1.15), but slightly decreased death or MI at 30 days (OR 0.92, 95%
      CI 0.86 to 0.99) and at six months (OR 0.88, 95% CI 0.81 to 0.96), although
      severe bleeding was increased (OR 1.27, 95% CI 1.12 to 1.43; ARI 1.4 per 1000).
      AUTHORS' CONCLUSIONS: When administered during PCI, intravenous IIb/IIIa blockers
      reduce the risk of death and of death or MI at 30 days and at six months, at a
      price of an increase in the risk of severe bleeding. The efficacy effects are
      homogeneous but are less marked in patients pre-treated with clopidogrel where
      they seem to be effective only in patients with ACS. When administered as initial
      medical treatment in patients with NSTEACS, these agents do not reduce mortality
      although they slightly reduce the risk of death or MI.

PMID- 20824832
TI  - Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal
      bleeding.
AB  - BACKGROUND: Bacterial infections are a frequent complication in patients with
      cirrhosis and upper gastrointestinal bleeding. Antibiotic prophylaxis seems to
      decrease the incidence of bacterial infections. Oral antibiotics, active against
      enteric bacteria, have been commonly used as antibiotic prophylaxis in patients
      with cirrhosis and upper gastrointestinal bleeding. This is an update of a
      Cochrane review first published in 2002. OBJECTIVES: To assess the benefits and
      harms of antibiotic prophylaxis in cirrhotic patients with upper gastrointestinal
      bleeding. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group
      Controlled Trials Register, The Cochrane Central Register of Controlled Trials
      (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index
      EXPANDED until June 2010. In addition, we handsearched the references of all
      identified studies. SELECTION CRITERIA: Randomised clinical trials comparing
      different types of antibiotic prophylaxis with no intervention, placebo, or
      another antibiotic to prevent bacterial infections in cirrhotic patients with
      upper gastrointestinal bleeding. DATA COLLECTION AND ANALYSIS: Three authors
      independently assessed trial quality, risk of bias, and extracted data. We
      contacted study authors for additional information. Association measures were
      relative risk (RR) for dichotomous outcomes and mean difference (MD) for
      continuous outcomes. MAIN RESULTS: Twelve trials (1241 patients) evaluated
      antibiotic prophylaxis compared with placebo or no antibiotic prophylaxis. All
      trials were at risk of bias. Antibiotic prophylaxis compared with no intervention
      or placebo was associated with beneficial effects on mortality (RR 0.79, 95% CI
      0.63 to 0.98), mortality from bacterial infections (RR 0.43, 95% CI 0.19 to
      0.97), bacterial infections (RR 0.36, 95% CI 0.27 to 0.49), rebleeding (RR 0.53,
      95% CI 0.38 to 0.74), days of hospitalisation (MD -1.91, 95% CI -3.80 to -0.02),
      bacteraemia (RR 0.25, 95% CI 0.15 to 0.40), pneumonia (RR 0.45, 95% CI 0.27 to
      0.75), spontaneous bacterial peritonitis (RR 0.29, 95% CI 0.15 to 0.57), and
      urinary tract infections (RR 0.23, 95% CI 0.12 to 0.41). No serious adverse
      events were reported. The trials showed no significant heterogeneity of effects.
      Another five trials (650 patients) compared different antibiotic regimens. Data
      could not be combined as each trial used different antibiotic regimen. None of
      the examined antibiotic regimen was superior to the control regimen regarding
      mortality or bacterial infections. AUTHORS' CONCLUSIONS: Prophylactic antibiotic
      use in patients with cirrhosis and upper gastrointestinal bleeding significantly
      reduced bacterial infections, and seems to have reduced all-cause mortality,
      bacterial infection mortality, rebleeding events, and hospitalisation length.
      These benefits were observed independently of the type of antibiotic used; thus,
      no specific antibiotic can be preferred. Therefore, antibiotic selection should
      be made considering local conditions such as bacterial resistance profile and
      treatment cost.

PMID- 20824833
TI  - Magnesium sulphate versus lytic cocktail for eclampsia.
AB  - BACKGROUND: Eclampsia, the occurrence of a seizure in association with pre
      eclampsia, is a rare but serious complication of pregnancy. A number of different
      anticonvulsants have been used to control eclamptic fits and to prevent further
      seizures. OBJECTIVES: The objective of this review was to assess the effects of
      magnesium sulphate compared with lytic cocktail (usually chlorpromazine,
      promethazine and pethidine) when used for the care of women with eclampsia.
      Magnesium sulphate is compared with diazepam and with phenytoin in other Cochrane
      reviews. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth
      Group's Trials Register (July 2010) and the Cochrane Central Register of Trials
      (The Cochrane Library 2010, Issue 2). SELECTION CRITERIA: Randomised trials
      comparing magnesium sulphate (intravenous or intramuscular administration) with
      lytic cocktail for women with a clinical diagnosis of eclampsia. DATA COLLECTION
      AND ANALYSIS: Two review authors (L Duley and D Chou) assessed trial quality and
      extracted data. MAIN RESULTS: We included three small trials (total 397 women) of
      average quality in the review. Magnesium sulphate was associated with fewer
      maternal deaths (risk ratio (RR) 0.14, 95% confidence interval (CI) 0.03 to 0.59;
      3 trials, 397 women) and was better at preventing further seizures (RR 0.06, 95%
      CI 0.03 to 0.12; 3 trials, 397 women) than lytic cocktail. Magnesium sulphate was
      also associated with less respiratory depression (RR 0.12, 95% CI 0.02 to 0.91; 2
      trials, 198 women), less coma (RR 0.04, 95% CI 0.00 to 0.74; 1 trial, 108 women),
      and less pneumonia (RR 0.20, 95% CI 0.06 to 0.67; 2 trials, 307 women). There was
      no clear difference in the RR for any death of the baby (RR 0.35, 95% CI 0.05 to
      2.38, random effects; 2 trials, 177 babies). AUTHORS' CONCLUSIONS: Magnesium
      sulphate, rather than lytic cocktail, for women with eclampsia reduces the RR of
      maternal death, of further seizures and of serious maternal morbidity
      (respiratory depression, coma, pneumonia). Magnesium sulphate is the
      anticonvulsant of choice for women with eclampsia; the use of lytic cocktail
      should be abandoned.

PMID- 20824834
TI  - Non-steroid agents for idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis is a chronic progressive lung disease
      with poor outcome and no effective treatment to date. This is an update of a
      Cochrane Review first published in 2003. OBJECTIVES: To assess the efficacy of
      non-steroid agents in adults with idiopathic pulmonary fibrosis. SEARCH STRATEGY:
      We searched the Cochrane Airways Group Register (30 March 2010), the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1,
      2010), Ovid MEDLINE to March week 5, 2010, EMBASE to week 13, 2010 and PubMed to
      April 2010, with additional handsearching, including abstracts of international
      conferences. We also contacted pharmaceutical companies and researchers in the
      field. SELECTION CRITERIA: Randomised studies comparing non-steroid drugs with
      placebo or steroids in adults with idiopathic pulmonary fibrosis. DATA COLLECTION
      AND ANALYSIS: Two authors independently assessed trial quality, extracted data
      and assessed risk of bias. We contacted pharmaceutical companies to obtain
      missing information, if any. We combined survival outcomes using Peto odds ratios
      or hazard ratios (HR). MAIN RESULTS: Fifteen trials involving 10 different drugs
      were included. Two trials enrolling 1156 patients compared interferon gamma-1beta
      with placebo: interferon gamma-1beta did not significantly improve survival (HR
      0.88, 95% CI 0.47 to 1.64; P = 0.68). Four trials involving 1155 patients
      compared pirfenidone with placebo. Three trials, conducted in 1046 patients,
      provided data on progression-free survival: pirfenidone significantly reduced the
      risk of disease progression by 30% (HR 0.70, 95% CI 0.56 to 0.88, P = 0.002).
      Data on the effect of pirfenidone on pulmonary function could only be assessed
      for two studies analysing 314 patients. Forced vital capacity or vital capacity
      was significantly improved by pirfenidone (mean difference 0.08 L, 95% CI 0.03 to
      0.13, P = 0.0006). AUTHORS' CONCLUSIONS: Based on available data, partly still
      unpublished, pirfenidone appears to improve progression-free survival and, to a
      lesser extent, pulmonary function in patients with idiopathic pulmonary fibrosis.
      More data are needed on overall survival and quality of life on treatment. From
      the studies in this review, interferon gamma-1beta has not been shown to affect
      survival. Other agents evaluated in single studies either failed to provide
      evidence for a benefit or need to be assessed in larger randomised controlled
      trials.

PMID- 20824836
TI  - Surgical interventions for treating acute Achilles tendon ruptures.
AB  - BACKGROUND: There is a lack of consensus on the best management of the acute
      Achilles tendon rupture. Treatment can be broadly classified into surgical (open
      or percutaneous) and non-surgical (cast immobilisation or functional bracing).
      OBJECTIVES: To evaluate the relative effects of surgical versus non-surgical
      treatment, or different surgical interventions, for acute Achilles tendon
      ruptures in adults. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and
      Muscle Trauma Group Specialised Register (July 2009), the Cochrane Central
      Register of Controlled Trials (The Cochrane Library 2009, Issue 3), MEDLINE (1966
      to 20th July 2009), EMBASE (1966 to 2009 week 29), CINAHL (1983 to July 2007) and
      reference lists of articles. SELECTION CRITERIA: All randomised and quasi
      randomised trials comparing surgical versus non-surgical treatment or different
      surgical methods for acute Achilles tendon ruptures in adults. DATA COLLECTION
      AND ANALYSIS: Two review authors independently selected potentially eligible
      trials; trials were then assessed for quality using a 10-item scale. Where
      possible, data were pooled. MAIN RESULTS: Twelve trials involving 844
      participants were included. One trial tested two comparisons.Quality assessment
      revealed a poor level of methodological rigour in many studies, particularly with
      regard to concealment of allocation and the lack of assessor blinding.Open
      surgical treatment compared with non-surgical treatment (6 trials, 536
      participants) was associated with a statistically significant lower risk of
      rerupture (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.21 to 0.77), but
      a higher risk of other complications including infection (RR 4.89, 95% CI 1.09 to
      21.91), adhesions and disturbed skin sensibility (numbness). Functional status
      including sporting activity was variably and often incompletely reported,
      including frequent use of non standardised outcome measures, and the results were
      inconclusive.Open surgical repair compared with percutaneous repair (4 trials,
      174 participants) was associated with a higher risk of infection (RR 9.32, 95% CI
      1.77 to 49.16). These figures should be interpreted with caution because of the
      small numbers involved. Similarly, no definitive conclusions could be made
      regarding different tendon repair techniques (3 trials, 147 participants).
      AUTHORS' CONCLUSIONS: Open surgical treatment of acute Achilles tendon ruptures
      significantly reduces the risk of rerupture compared with non-surgical treatment,
      but produces significantly higher risks of other complications, including wound
      infection. The latter may be reduced by performing surgery percutaneously.

PMID- 20824835
TI  - Single dose dipyrone for acute postoperative pain.
AB  - BACKGROUND: Dipyrone (metamizole) is a non-steroidal anti-inflammatory drug used
      in some countries to treat pain (postoperative, colic, cancer, and migraine); it
      is banned in others because of an association with life-threatening blood
      agranulocytosis. This review updates a 2001 Cochrane review, and no relevant new
      studies were identified, but additional outcomes were sought. OBJECTIVES: To
      assess the efficacy and adverse events of single dose dipyrone in acute
      postoperative pain. SEARCH STRATEGY: The earlier review searched CENTRAL,
      MEDLINE, EMBASE, LILACS and the Oxford Pain Relief Database to December 1999. For
      the update we searched CENTRAL, MEDLINE,EMBASE and LILACS to February 2010.
      SELECTION CRITERIA: Single dose, randomised, double-blind, placebo or active
      controlled trials of dipyrone for relief of established moderate to severe
      postoperative pain in adults. We included oral, rectal, intramuscular or
      intravenous administration of study drugs. DATA COLLECTION AND ANALYSIS: Studies
      were assessed for methodological quality and data extracted by two review authors
      independently. Summed total pain relief over six hours (TOTPAR) was used to
      calculate the number of participants achieving at least 50% pain relief. Derived
      results were used to calculate, with 95% confidence intervals, relative benefit
      compared to placebo, and the number needed to treat (NNT) for one participant to
      experience at least 50% pain relief over six hours. Use and time to use of rescue
      medication were additional measures of efficacy. Information on adverse events
      and withdrawals was collected. MAIN RESULTS: Fifteen studies tested mainly 500 mg
      oral dipyrone (173 participants), 2.5 g intravenous dipyrone (101), 2.5 g
      intramuscular dipyrone (99); fewer than 60 participants received any other dose.
      All studies used active controls (ibuprofen, paracetamol, aspirin, flurbiprofen,
      ketoprofen, dexketoprofen, ketorolac, pethidine, tramadol, suprofen); eight used
      placebo controls.Over 70% of participants experienced at least 50% pain relief
      over 4 to 6 hours with oral dipyrone 500 mg compared to 30% with placebo in five
      studies (288 participants; NNT 2.4 (1.9 to 3.2)). Fewer participants needed
      rescue medication with dipyrone (7%) than with placebo (34%; four studies, 248
      participants). There was no difference in participants experiencing at least 50%
      pain relief with 2.5 g intravenous dipyrone and 100 mg intravenous tramadol (70%
      vs 65%; two studies, 200 participants). No serious adverse events were reported.
      AUTHORS' CONCLUSIONS: Based on very limited information, single dose dipyrone 500
      mg provides good pain relief to 70% of patients. For every five individuals given
      dipyrone 500 mg, two would experience this level of pain relief who would not
      have done with placebo, and fewer would need rescue medication, over 4 to 6
      hours.

PMID- 20824837
TI  - Acamprosate for alcohol dependence.
AB  - BACKGROUND: Alcohol dependence is among the main leading health risk factors in
      most developed and developing countries. Therapeutic success of psychosocial
      programs for relapse prevention is moderate, but could potentially be increased
      by an adjuvant treatment with the glutamate antagonist acamprosate. OBJECTIVES:
      To determine the effectiveness and tolerability of acamprosate in comparison to
      placebo and other pharmacological agents. SEARCH STRATEGY: We searched the
      Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE and
      CINAHL in January 2009 and inquired manufacturers and researchers for unpublished
      trials. SELECTION CRITERIA: All double-blind randomised controlled trials (RCTs)
      which compare the effects of acamprosate with placebo or active control on
      drinking-related outcomes. DATA COLLECTION AND ANALYSIS: Two authors
      independently extracted data. Trial quality was assessed by one author and cross
      checked by a second author. Individual patient data (IPD) meta-analyses were used
      to verify the primary effectiveness outcomes. MAIN RESULTS: 24 RCTs with 6915
      participants fulfilled the criteria of inclusion and were included in the review.
      Compared to placebo, acamprosate was shown to significantly reduce the risk of
      any drinking RR 0.86 (95% CI 0.81 to 0.91); NNT 9.09 (95% CI 6.66 to 14.28) and
      to significantly increase the cumulative abstinence duration MD 10.94 (95% CI
      5.08 to 16.81), while secondary outcomes (gamma-glutamyltransferase, heavy
      drinking) did not reach statistical significance. Diarrhea was the only side
      effect that was more frequently reported under acamprosate than placebo RD 0.11
      (95% 0.09 to 0.13); NNTB 9.09 (95% CI 7.69 to 11.11). Effects of industry
      sponsored trials RR 0.88 (95% 0.80 to 0.97) did not significantly differ from
      those of non-profit funded trials RR 0.88 (95% CI 0.81 to 0.96). In addition, the
      linear regression test did not indicate a significant risk of publication bias (p
      = 0.861). AUTHORS' CONCLUSIONS: Acamprosate appears to be an effective and safe
      treatment strategy for supporting continuous abstinence after detoxification in
      alcohol dependent patients. Even though the sizes of treatment effects appear to
      be rather moderate in their magnitude, they should be valued against the
      background of the relapsing nature of alcoholism and the limited therapeutic
      options currently available for its treatment.

PMID- 20824838
TI  - Corticosteroids for acute bacterial meningitis.
AB  - BACKGROUND: In experimental studies, the outcome of bacterial meningitis has been
      related to the severity of inflammation in the subarachnoid space.
      Corticosteroids reduce this inflammatory response. OBJECTIVES: To examine the
      effect of adjuvant corticosteroid therapy versus placebo on mortality, hearing
      loss and neurological sequelae in people of all ages with acute bacterial
      meningitis. SEARCH STRATEGY: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2010, issue 1), MEDLINE (1966
      to February 2010), EMBASE (1974 to February 2010) and Current Contents (2001 to
      February 2010). SELECTION CRITERIA: Randomised controlled trials (RCTs) of
      corticosteroids for acute bacterial meningitis. DATA COLLECTION AND ANALYSIS: We
      scored RCTs for methodological quality. We collected outcomes and adverse
      effects. We performed subgroup analyses for children and adults, causative
      organisms, low-income versus high-income countries, time of steroid
      administration and study quality. MAIN RESULTS: Twenty-four studies involving
      4041 participants were included. Similar numbers of participants died in the
      corticosteroid and placebo groups (18.0% versus 20.0%; risk ratio (RR) 0.92, 95%
      confidence interval (CI) 0.82 to 1.04, P = 0.18). There was a trend towards lower
      mortality in adults receiving corticosteroids (RR 0.74, 95% CI 0.53 to 1.05, P =
      0.09). Corticosteroids were associated with lower rates of severe hearing loss
      (RR 0.67, 95% CI 0.51 to 0.88), any hearing loss (RR 0.76, 95% CI 0.64 to 0.89)
      and neurological sequelae (RR 0.83, 95% CI 0.69 to 1.00).Subgroup analyses for
      causative organisms showed that corticosteroids reduced severe hearing loss in
      Haemophilus influenzae meningitis (RR 0.34, 95% CI 0.20 to 0.59) and reduced
      mortality in Streptococcus pneumoniae meningitis (RR 0.84, 95% CI 0.72 to
      0.98).In high-income countries, corticosteroids reduced severe hearing loss (RR
      0.51, 95% CI 0.35 to 0.73), any hearing loss (RR 0.58, 95% CI 0.45 to 0.73) and
      short-term neurological sequelae (RR 0.64, 95% CI 0.48 to 0.85). There was no
      beneficial effect of corticosteroid therapy in low-income countries.Subgroup
      analysis for study quality showed no effect of corticosteroids on severe hearing
      loss in high quality studies.Corticosteroid treatment was associated with an
      increase in recurrent fever (RR 1.27, 95% CI 1.09 to 1.47), but not with other
      adverse events. AUTHORS' CONCLUSIONS: Corticosteroids significantly reduced
      hearing loss and neurological sequelae, but did not reduce overall mortality.
      Data support the use of corticosteroids in patients with bacterial meningitis in
      high-income countries. We found no beneficial effect in low-income countries.

PMID- 20824839
TI  - Follicular flushing during oocyte retrieval in assisted reproductive techniques.
AB  - BACKGROUND: Ultrasound guided transvaginal aspiration of oocytes has replaced
      other methods of oocyte retrieval for in vitro fertilization (IVF) and
      intracytoplasmic sperm injection (ICSI). However, there is controversy over
      whether flushing yields a larger number of oocytes and a higher potential for
      pregnancy than aspiration only. OBJECTIVES: To determine whether follicular
      aspiration and flushing increases live birth or ongoing pregnancy rates and the
      number of oocytes over aspiration alone in women undergoing IVF and ICSI. SEARCH
      STRATEGY: We searched the Menstrual Disorders and Subfertility Group Specialised
      Register of controlled trials, MEDLINE, EMBASE, Cochrane Central Register of
      Controlled Trials (CENTRAL), PsycINFO and the citation lists of relevant
      publications (to April 2010). SELECTION CRITERIA: Randomised controlled trials
      that compared follicular aspiration and flushing with aspiration alone were
      included. Trials were excluded if the flushing method comparison was confounded
      by comparisons of other methods. DATA COLLECTION AND ANALYSIS: Eligible studies
      were assessed for methodological quality. For dichotomous data, odds ratios (OR)
      and 95% confidence intervals (CI) were calculated. For continuous data, mean
      differences were reported. The heterogeneity of the studies was examined by using
      statistical tests of homogeneity and the I(2) statistic. MAIN RESULTS: No studies
      reported on the primary outcome of live birth. There was no evidence (3 studies,
      164 patients) to suggest an association between follicular aspiration and
      flushing and ongoing or clinical pregnancy per woman randomised (OR 1.17, 95% CI
      0.57 to 2.38). There was no evidence of a difference in adverse events reported
      between follicular aspiration and flushing and aspiration only. There was no
      evidence of significant differences in increased oocyte yield per woman
      randomised (1 study, 44 patients). Without flushing the operative time was
      significantly shorter, by 3 to 15 minutes (3 studies, P < 0.001) and the dose of
      pethidine required was significantly less (50 mg versus 100 mg, P < 0.00001).
      AUTHORS' CONCLUSIONS: There is no evidence that follicular aspiration and
      flushing is associated with improved clinical or ongoing pregnancy rates, nor an
      increase in oocyte yield. The operative time is significantly longer and more
      opiate analgesia is required for pain relief during oocyte retrieval. There is a
      lack of evidence regarding the effect of follicular aspiration and flushing on
      live birth rates in the identified data.

PMID- 20824840
TI  - WITHDRAWN: Immunoglobulin treatment for respiratory syncytial virus infection.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis and pneumonia
      hospitalise hundreds of thousands of infants every year. Treatment is largely
      supportive therapy, (for example, oxygen, fluids and occasionally mechanical
      ventilation). Ribavirin, an antiviral agent, is licensed for severe RSV
      infection, although systematic reviews find it of no benefit. Passive protection
      against RSV can be achieved through monthly intramuscular injections of the
      humanised monoclonal anti-RSV antibody palivizumab (Synagis), and yields a 55%
      reduction in RSV hospitalisation in susceptible infants. This review assesses
      immunoglobulin treatment of RSV infection rather than its role as a prophylactic
      measure. OBJECTIVES: To assess the efficacy of adding human or humanised
      immunoglobulin therapy to supportive therapy in infants hospitalised with
      laboratory-determined RSV infection. SEARCH STRATEGY: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2006,
      issue 1) which contains the Acute Respiratory Infections Group's specialized
      regsiter, MEDLINE (1966 to Week 4, January 2006) and EMBASE (1980 to September
      2005). We also ran searches of reference lists of relevant trials and review
      articles and searches of personal files. We did not impose any language
      restrictions. SELECTION CRITERIA: We selected randomised controlled trials (RCTs)
      that compared immunoglobulin treatment with a placebo control in children
      hospitalised for RSV infection with bronchiolitis or pneumonia or other lower
      respiratory tract infection (LRTI) with laboratory-documented RSV infection. The
      primary outcomes of interest were mortality, length of hospitalisation, length of
      ventilation and oxygen dependence. Secondary outcome measures were pulmonary
      function and re-hospitalisations for recurrent breathing difficulties in
      subsequent years. Any adverse effects of the treatments were also noted, for
      example, hypersensitivity reactions. DATA COLLECTION AND ANALYSIS: Data were
      extracted but cross-comparison was not possible due to the shortage of studies
      and lack of comparative measurements. MAIN RESULTS: Four papers fitted the search
      criteria. None demonstrated statistically significant benefit of intravenous
      immunoglobulin (IVIG) treatment added to supportive care compared with supportive
      care alone. The evidence does not support a role for RSVIG in such a setting,
      with the doses used in the studies. AUTHORS' CONCLUSIONS: The evidence on the
      role of respiratory syncytial virus immunoglobulin (RSVIG) in treating RSV severe
      infections is limited. Future research might consider using stronger titres of
      neutralising antibodies; and further analyse severely ill children (who might
      respond differentially compared to those less ill, but yet hospitalised).

PMID- 20824841
TI  - Non-hormonal interventions for hot flushes in women with a history of breast
      cancer.
AB  - BACKGROUND: Hot flushes are common in women with a history of breast cancer.
      Hormonal therapies are known to reduce these symptoms but are not recommended in
      women with a history of breast cancer due to their potential adverse effects. The
      efficacy of non-hormonal therapies is still uncertain. OBJECTIVES: To assess the
      efficacy of non-hormonal therapies in reducing hot flushes in women with a
      history of breast cancer. SEARCH STRATEGY: We searched the Cochrane Breast Cancer
      Group Specialised Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE,
      LILACS, CINAHL, PsycINFO (August 2008) and WHO ICTRP Search Portal. We
      handsearched reference lists of reviews and included articles, reviewed
      conference proceedings and contacted experts. SELECTION CRITERIA: Randomized
      controlled trials (RCTs) comparing non-hormonal therapies with placebo or no
      therapy for reducing hot flushes in women with a history of breast cancer. DATA
      COLLECTION AND ANALYSIS: Two authors independently selected potentially relevant
      studies, decided upon their inclusion and extracted data on participant
      characteristics, interventions, outcomes and the risk of bias of included
      studies. MAIN RESULTS: Sixteen RCTs met our inclusion criteria. We included six
      studies on selective serotonin (SSRI) and serotonin-norepinephrine (SNRI)
      reuptake inhibitors, two on clonidine, one on gabapentin, two each on relaxation
      therapy and homeopathy, and one each on vitamin E, magnetic devices and
      acupuncture. The risk of bias of most studies was rated as low or moderate. Data
      on continuous outcomes were presented inconsistently among studies, which
      precluded the possibility of pooling the results. Three pharmacological
      treatments (SSRIs and SNRIs, clonidine and gabapentin) reduced the number and
      severity of hot flushes. One study assessing vitamin E did not show any
      beneficial effect. One of two studies on relaxation therapy showed a significant
      benefit. None of the other non-pharmacological therapies had a significant
      benefit. Side-effects were inconsistently reported. AUTHORS' CONCLUSIONS:
      Clonidine, SSRIs and SNRIs, gabapentin and relaxation therapy showed a mild to
      moderate effect on reducing hot flushes in women with a history of breast cancer.

PMID- 20824842
TI  - Interventions to improve hand hygiene compliance in patient care.
AB  - BACKGROUND: Health care-associated infection is a major cause of morbidity and
      mortality. Hand hygiene is regarded as an effective preventive measure.
      OBJECTIVES: To update the review done in 2007, to assess the short and longer
      term success of strategies to improve hand hygiene compliance and to determine
      whether a sustained increase in hand hygiene compliance can reduce rates of
      health care-associated infection. SEARCH STRATEGY: We conducted electronic
      searches of: the Cochrane Central Register of Controlled Trials; the Cochrane
      Effective Practice and Organisation of Care Group specialised register of trials;
      MEDLINE; PubMed; EMBASE; CINAHL; and the BNI. Originally searched to July 2006,
      for the update databases were searched from August 2006 until November 2009.
      SELECTION CRITERIA: Randomised controlled trials, controlled clinical trials,
      controlled before and after studies, and interrupted time series analyses meeting
      explicit entry and quality criteria used by the Cochrane Effective Practice and
      Organisation of Care Group were eligible for inclusion. Studies reporting
      indicators of hand hygiene compliance and proxy indicators such as product use
      were considered. Self-reported data were not considered a valid measure of
      compliance. Studies to promote hand hygiene compliance as part of a care bundle
      approach were included, providing data relating specifically to hand hygiene were
      presented separately. Studies were excluded if hand hygiene was assessed in
      simulations, non-clinical settings or the operating theatre setting. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed
      data quality. MAIN RESULTS: Four studies met the criteria for the review: two
      from the original review and two from the update. Two studies evaluated simple
      education initiatives, one using a randomized clinical trial design and the other
      a controlled before and after design. Both measured hand hygiene compliance by
      direct observation. The other two studies were both interrupted times series
      studies. One study presented three separate interventions within the same paper:
      simple substitutions of product and two multifaceted campaigns, one of which
      included involving practitioners in making decisions about choice of hand hygiene
      products and the components of the hand hygiene program. The other study also
      presented two separate multifaceted campaigns, one of which involved application
      of social marketing theory. In these two studies follow-up data collection
      continued beyond twelve months, and a proxy measure of hand hygiene compliance
      (product use) was recorded. Microbiological data were recorded in one study. Hand
      hygiene compliance increased for one of the studies where it was measured by
      direct observation, but the results from the other study were not conclusive.
      Product use increased in the two studies in which it was reported, with
      inconsistent results reported for one initiative. MRSA incidence decreased in the
      one study reporting microbiological data. AUTHORS' CONCLUSIONS: The quality of
      intervention studies intended to increase hand hygiene compliance remains
      disappointing. Although multifaceted campaigns with social marketing or staff
      involvement appear to have an effect, there is insufficient evidence to draw a
      firm conclusion. There remains an urgent need to undertake methodologically
      robust research to explore the effectiveness of soundly designed and implemented
      interventions to increase hand hygiene compliance.

PMID- 20824843
TI  - Interventions to increase influenza vaccination rates of those 60 years and older
      in the community.
AB  - BACKGROUND: Although the evidence to support influenza vaccination is poor, it is
      promoted by many health authorities. There is uncertainty about the effectiveness
      of interventions to increase influenza vaccination rates in those 60 years or
      older. OBJECTIVES: To assess effects of interventions to increase influenza
      vaccination rates in those 60 or older. SEARCH STRATEGY: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2010,
      issue 3), containing the Cochrane Acute Respiratory Infections Group's
      Specialized Register, MEDLINE (January 1950 to July 2010), PubMed (January 1950
      to July 2010), EMBASE (1980 to 2010 Week 28), AgeLine (1978 to July 2010), ERIC
      (1965 to July 2010) and CINAHL (1982 to July 2010). SELECTION CRITERIA:
      Randomized controlled trials (RCTs) to increase influenza vaccination rates in
      those aged 60 years and older, recording influenza vaccination status either
      through clinic records, billing data or local/national vaccination registers.
      DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study
      quality and extracted data. MAIN RESULTS: Forty-four RCTs were included. All
      included RCTs studied seniors in the community and in high-income countries. No
      RCTs of society-level interventions were included. Heterogeneity was marked and
      meta-analysis was limited. Only five RCTs were graded at low and six at moderate
      risk of bias. They included three of 13 personalized postcard interventions (all
      three with the 95% confidence interval (CI) above unity), two of the four home
      visit interventions (both with 95% CI above unity, but one a small study), three
      of the four reminder to physicians interventions (none with 95% CI above unity)
      and three of the four facilitator interventions (one with 95% CI above unity, and
      one P < 0.01). The other 33 RCTs were at high risk of bias and no recommendations
      for practice can be drawn. AUTHORS' CONCLUSIONS: Personalized postcards or phone
      calls are effective, and home visits, and facilitators, may be effective.
      Reminders to physicians are not. There is insufficient good evidence for other
      interventions.

PMID- 20824844
TI  - Cognitive behavioural therapy for tinnitus.
AB  - BACKGROUND: This is an update of a Cochrane Review originally published in Issue
      1, 2007 of The Cochrane Library.Tinnitus is an auditory perception that can be
      described as the experience of sound, in the ear or in the head, in the absence
      of external acoustic stimulation. Cognitive behavioural therapy (CBT) uses
      relaxation, cognitive restructuring of the thoughts and exposure to exacerbating
      situations in order to promote habituation and may benefit tinnitus patients, as
      may the treatment of associated psychological conditions. OBJECTIVES: To assess
      whether CBT is effective in the management of patients suffering from tinnitus.
      SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group
      Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL);
      PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific
      Abstracts; PsycINFO; ISRCTN and additional sources for published and unpublished
      trials. The date of the most recent search was 6 May 2010. SELECTION CRITERIA:
      Randomised controlled trials in which patients with unilateral or bilateral
      tinnitus as their main symptom received cognitive behavioural treatment. DATA
      COLLECTION AND ANALYSIS: One review author (PMD) assessed every report identified
      by the search strategy. Three authors (PMD, AW and MT) assessed the
      methodological quality and applied inclusion/exclusion criteria. Two authors (PMD
      and RP) extracted data and conducted the meta-analysis. The four authors
      contributed to the final text of the review. MAIN RESULTS: Eight trials
      comprising 468 participants were included.For the primary outcome of subjective
      tinnitus loudness we found no evidence of a difference between CBT and no
      treatment or another intervention (yoga, education and 'minimal contact -
      education').In the secondary outcomes we found evidence that quality of life
      scores were improved in participants who had tinnitus when comparing CBT to no
      treatment or another intervention (education and 'minimal contact education'). We
      also found evidence that depression scores improved when comparing CBT to no
      treatment. We found no evidence of benefit in depression scores when comparing
      CBT to other treatments (yoga, education and 'minimal contact - education').There
      were no adverse/side effects reported in any trial. AUTHORS' CONCLUSIONS: In six
      studies we found no evidence of a significant difference in the subjective
      loudness of tinnitus.However, we found a significant improvement in depression
      score (in six studies) and quality of life (decrease of global tinnitus severity)
      in another five studies, suggesting that CBT has a positive effect on the
      management of tinnitus.

PMID- 20824845
TI  - Heparin and related substances for preventing diabetic kidney disease.
AB  - BACKGROUND: Diabetic kidney disease (DKD, also called diabetic nephropathy, DN)
      is the major cause of end-stage kidney disease (ESKD) in many countries and is
      associated with increased morbidity and mortality as compared to other causes of
      kidney disease. One of the pathological changes of DKD is the thickening of the
      glomerular basement membrane, mesangial expansion and proliferation. The presence
      of the glycosaminoglycan side chains of heparan sulfate proteoglycan, an
      important constituent of the glomerular basement membrane, is decreased in DKD
      proportionally to the increasing degree of proteinuria. Research on animals has
      suggested that heparin and related substances may prevent glomerular membrane
      thickening. However, it is not known whether heparin and related substances can
      prevent the onset of DKD and, therefore, be recommended for primary prevention of
      this condition. OBJECTIVES: To assess the benefits and harms of heparin and
      related substances for preventing the onset of DKD. SEARCH STRATEGY: We searched
      the Cochrane Renal Group's Specialised Register and the Cochrane Central Register
      of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 2, 2009). We also
      searched MEDLINE (1966 to June 2009), EMBASE (1980 to June 2009), China
      Biological Medicine (CBM; 1979 to June 2009), VIP Chinese Science and Technique
      Journals Database (until June 2009), China National Infrastructure (CNKI) (until
      June 2009) and Wanfang database (until June 2009). Reference lists of nephrology
      textbooks, review articles and relevant studies were also searched. SELECTION
      CRITERIA: All relevant randomised controlled trials (RCTs) and quasi-RCTs looking
      at the benefits and harms of heparin and related substances for preventing the
      onset of DKD were eligible. DATA COLLECTION AND ANALYSIS: We planned for two
      authors to extract data independently using a self-developed data extraction form
      and enter them into RevMan 5 software; for meta-analyses to be performed when
      more than one study provided data on a comparable outcome on sufficiently similar
      patients; for random-effects analyses to be performed whenever heterogeneity
      between results appeared to be present; and for standardised differences in mean
      outcome measures to be used due to the use of different scales and periods of
      treatment. MAIN RESULTS: No studies met our inclusion criteria. AUTHORS'
      CONCLUSIONS: Rigorously well-designed, randomised, multi-centre, large-sample
      studies of heparin and related substances for preventing the onset of DKD are
      needed.

PMID- 20824846
TI  - Interventions for replacing missing teeth: dental implants in fresh extraction
      sockets (immediate, immediate-delayed and delayed implants).
AB  - BACKGROUND: 'Immediate' implants are placed in dental sockets just after tooth
      extraction. 'Immediate-delayed' implants are those implants inserted after weeks
      up to about a couple of months to allow for soft tissue healing. 'Delayed'
      implants are those placed thereafter in partially or completely healed bone. The
      potential advantages of immediate implants are that treatment time can be
      shortened and that bone volumes might be partially maintained thus possibly
      providing good aesthetic results. The potential disadvantages are an increased
      risk of infection and failures. After implant placement in postextractive sites,
      gaps can be present between the implant and the bony walls. It is possible to
      fill these gaps and to augment bone simultaneously to implant placement. There
      are many techniques to achieve this but it is unclear when augmentation is needed
      and which could be the best augmentation technique. OBJECTIVES: To evaluate
      success, complications, aesthetics and patient satisfaction between 'immediate',
      'immediate-delayed' and 'delayed' implants.To evaluate whether and when
      augmentation procedures are necessary and which is the most effective technique.
      SEARCH STRATEGY: The Cochrane Oral Health Group's Trials Register (to 2 June
      2010), CENTRAL (The Cochrane Library 2010, Issue 2), MEDLINE via OVID (1950 - 2
      June 2010) and EMBASE via OVID (1980 - 2 June 2010) were searched. Several dental
      journals were handsearched. SELECTION CRITERIA: Randomised controlled trials
      (RCTs) comparing immediate, immediate-delayed, and delayed implants, or comparing
      various bone augmentation procedures around the inserted implants, reporting the
      outcome of the interventions to at least 1 year after functional loading. DATA
      COLLECTION AND ANALYSIS: Screening of eligible studies, assessment of the
      methodological quality of the trials and data extraction were conducted
      independently and in duplicate. Trial authors were contacted for any missing
      information. Results were expressed as random-effects models using mean
      differences for continuous outcomes and risk ratios (RR) for dichotomous outcomes
      with 95% confidence intervals (CIs). The statistical unit of the analysis was the
      patient. MAIN RESULTS: Fourteen eligible RCTs were identified but only seven
      trials could be included. Four RCTs evaluated implant placement timing. Two RCTs
      compared immediate versus delayed implants in 126 patients and found no
      statistically significant differences. One RCT compared immediate-delayed versus
      delayed implants in 46 patients. After 2 years patients in the immediate-delayed
      group perceived the time to functional loading significantly shorter, were more
      satisfied and independent blinded assessor judged the level of the perimplant
      marginal mucosa in relation to that of the adjacent teeth as more appropriate (RR
      = 1.68; 95% CI 1.04 to 2.72). These differences disappeared 5 years after loading
      but significantly more complications occurred in the immediate-delayed group (RR
      = 4.20; 95% CI 1.01 to 17.43). One RCT compared immediate with immediately
      delayed implants in 16 patients for 2 years and found no differences. Three RCTs
      evaluated different techniques of bone grafting for implants immediately placed
      in extraction sockets. No statistically significant difference was observed when
      evaluating whether autogenous bone is needed in postextractive sites (1 trial
      with 26 patients) or which was the most effective augmentation technique (2
      trials with 56 patients). AUTHORS' CONCLUSIONS: There is insufficient evidence to
      determine possible advantages or disadvantages of immediate, immediate-delayed or
      delayed implants, therefore these preliminary conclusions are based on few
      underpowered trials often judged to be at high risk of bias. There is a
      suggestion that immediate and immediate-delayed implants may be at higher risks
      of implant failures and complications than delayed implants on the other hand the
      aesthetic outcome might be better when placing implants just after teeth
      extraction. There is not enough reliable evidence supporting or refuting the need
      for augmentation procedures at immediate implants placed in fresh extraction
      sockets or whether any of the augmentation techniques is superior to the others.

PMID- 20824847
TI  - Interventions for the treatment of oral cavity and oropharyngeal cancer:
      chemotherapy.
AB  - BACKGROUND: Oral cavity and oropharyngeal cancers are frequently described as
      part of a group of oral cancers or head and neck cancer. Treatment of oral cavity
      cancer is generally surgery followed by radiotherapy, whereas oropharyngeal
      cancers, which are more likely to be advanced at the time of diagnosis, are
      managed with radiotherapy or chemoradiation. Surgery for oral cancers can be
      disfiguring and both surgery and radiotherapy have significant functional side
      effects, notably impaired ability to eat, drink and talk. The development of new
      chemotherapy agents, new combinations of agents and changes in the relative
      timing of surgery, radiotherapy, and chemotherapy treatments may potentially
      bring about increases in both survival and quality of life for this group of
      patients. OBJECTIVES: To determine whether chemotherapy, in addition to
      radiotherapy and/or surgery for oral cavity and oropharyngeal cancer results in
      improved survival, disease free survival, progression free survival, locoregional
      control and reduced recurrence of disease. To determine which regimen and time of
      administration (induction, concomitant or adjuvant) is associated with better
      outcomes. SEARCH STRATEGY: Electronic searches of the Cochrane Oral Health
      Group's Trials Register, CENTRAL, MEDLINE, EMBASE, AMED were undertaken on 28th
      July 2010. Reference lists of recent reviews and included studies were also
      searched to identify further trials. SELECTION CRITERIA: Randomised controlled
      trials where more than 50% of participants had primary tumours in the oral cavity
      or oropharynx, and which compared the addition of chemotherapy to other
      treatments such as radiotherapy and/or surgery, or compared two or more
      chemotherapy regimens or modes of administration, were included. DATA COLLECTION
      AND ANALYSIS: Trials which met the inclusion criteria were assessed for risk of
      bias using six domains: sequence generation, allocation concealment, blinding,
      completeness of outcome data, selective reporting and other possible sources of
      bias. Data were extracted using a specially designed form and entered into the
      characteristics of included studies table and the analysis sections of the
      review. The proportion of participants in each trial with oral cavity and
      oropharyngeal cancers are recorded in Additional Table 1. MAIN RESULTS: There was
      no statistically significant improvement in overall survival associated with
      induction chemotherapy compared to locoregional treatment alone in 25 trials
      (hazard ratio (HR) of mortality 0.92, 95% confidence interval (CI) 0.84 to 1.00).
      Post-surgery adjuvant chemotherapy was associated with improved overall survival
      compared to surgery +/- radiotherapy alone in 10 trials (HR of mortality 0.88,
      95% CI 0.79 to 0.99), and there was an additional benefit of adjuvant concomitant
      chemoradiotherapy compared to radiotherapy in 4 of these trials (HR of mortality
      0.84, 95% CI 0.72 to 0.98). Concomitant chemoradiotherapy resulted in improved
      survival compared to radiotherapy alone in patients whose tumours were considered
      unresectable in 25 trials (HR of mortality 0.79, 95% CI 0.74 to 0.84). However,
      the additional toxicity attributable to chemotherapy in the combined regimens
      remains unquantified. AUTHORS' CONCLUSIONS: Chemotherapy, in addition to
      radiotherapy and surgery, is associated with improved overall survival in
      patients with oral cavity and oropharyngeal cancers. Induction chemotherapy is
      associated with a 9% increase in survival and adjuvant concomitant
      chemoradiotherapy is associated with a 16% increase in overall survival following
      surgery. In patients with unresectable tumours, concomitant chemoradiotherapy
      showed a 22% benefit in overall survival compared with radiotherapy alone.

PMID- 20824848
TI  - Octreotide for the treatment of chylothorax in neonates.
AB  - BACKGROUND: Routine care for chylothorax in neonate includes either conservative
      or surgical approaches. Octreotide, a somatostatin analogue, has been used for
      the management of patients with refractory chylothorax not responding to
      conservative management. OBJECTIVES: To assess the efficacy and safety of
      octreotide in the treatment of chylothorax in neonates. SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library), MEDLINE and EMBASE (to March 7, 2010). We assessed the
      reference lists of identified trials and abstracts from the annual meetings of
      the Pediatric Academic Societies published in Pediatric Research (2002 to 2009)
      without language restrictions. SELECTION CRITERIA: We planned to include
      randomised or quasi-randomised controlled trials of octreotide in the treatment
      of congenital or acquired chylothorax in term or preterm neonates, with any dose,
      duration or route of administration. DATA COLLECTION AND ANALYSIS: Data on
      primary (amount of fluid drainage, respiratory support, mortality) and secondary
      outcomes (side effects) were planned to be collected and analysed using mean
      difference, relative risk and risk difference with 95% confidence intervals. MAIN
      RESULTS: No randomised controlled trials were identified. Nineteen case reports
      of 20 neonates with chylothorax in whom octreotide was used either subcutaneously
      or intravenously were identified. Fourteen case reports described successful use
      (resolution of chylothorax), four reported failure (no resolution) and one
      reported equivocal results following use of octreotide. The timing of initiation,
      dose, duration and frequency of doses varied markedly. Gastrointestinal
      intolerance and clinical presentations suggestive of necrotizing enterocolitis
      and transient hypothyroidism were reported as side effects. AUTHORS' CONCLUSIONS:
      No practice recommendation can be made based on the evidence identified in this
      review. A prospective registry of chylothorax patients and a subsequent
      multicenter randomised controlled trial are needed to assess the safety and
      efficacy of octreotide in the treatment of chylothorax in neonates.

PMID- 20824849
TI  - Occupational therapy for cognitive impairment in stroke patients.
AB  - BACKGROUND: Cognitive impairment is a frequent consequence of stroke and can
      impact on a person's ability to perform everyday activities. There are a number
      of different intervention strategies that occupational therapists may use when
      working with people who have cognitive impairment post-stroke. OBJECTIVES: To
      determine whether occupational therapy improves functional performance of basic
      activities of daily living (ADL) and specific cognitive abilities in people who
      have cognitive impairment following a stroke. SEARCH STRATEGY: We searched the
      Cochrane Stroke Group Trials Register (last searched May 2009), the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1,
      2009), MEDLINE (1966 to April 2009), EMBASE (1980 to April 2009), CINAHL (1982 to
      April 2009), PsycINFO (1840 to April 2009), PsycBITE, OTseeker and Dissertation
      Abstracts (the latest three were searched up to April 2009). In an effort to
      identify further published, unpublished, and ongoing trials, we also tracked
      relevant references through the cited reference search in Science Citation Index
      (SCI) and Social Science Citation Index (SSCI), reviewed the reference lists of
      relevant studies and reviews, handsearched relevant occupational therapy
      journals, and contacted key researchers in the area. SELECTION CRITERIA:
      Randomised and quasi-randomised controlled trials that evaluated an intervention
      focused on providing cognitive retraining to adults with clinically defined
      stroke and confirmed cognitive impairment. The intervention needed either to be
      provided by an occupational therapist or given under the supervision of an
      occupational therapist. DATA COLLECTION AND ANALYSIS: Two review authors
      independently examined the abstracts that might meet the inclusion criteria,
      assessed the quality and extracted data. We have presented results using mean
      differences. MAIN RESULTS: We included one trial with 33 participants in this
      review. We found no difference between groups for the two relevant outcomes that
      were measured: improvement in time judgement skills and improvement in basic ADLs
      on the Barthel Index. AUTHORS' CONCLUSIONS: The effectiveness of occupational
      therapy for cognitive impairment post-stroke remains unclear. The potential
      benefits of cognitive retraining delivered as part of occupational therapy on
      improving basic daily activity function or specific cognitive abilities, or both,
      of people who have had a stroke cannot be supported or refuted by the evidence
      included in this review. More research is required.

PMID- 20824850
TI  - Interactive computer-based interventions for sexual health promotion.
AB  - BACKGROUND: Sexual health promotion is a major public health challenge; there is
      huge potential for health promotion via technology such as the Internet.
      OBJECTIVES: To determine effects of interactive computer-based interventions
      (ICBI) for sexual health promotion, considering cognitive, behavioural,
      biological and economic outcomes. SEARCH STRATEGY: We searched more than thirty
      databases for randomised controlled trials (RCTs) on ICBI and sexual health,
      including CENTRAL, DARE, MEDLINE, EMBASE, CINAHL, British Nursing Index, and
      PsycINFO. We also searched reference lists of published studies and contacted
      authors. All databases were searched from start date to November 2007, with no
      language restriction. SELECTION CRITERIA: RCTs of interactive computer-based
      interventions for sexual health promotion, involving participants of any age,
      gender, sexual orientation, ethnicity or nationality. 'Interactive' was defined
      as packages that require contributions from users to produce tailored material
      and feedback that is personally relevant. DATA COLLECTION AND ANALYSIS: Two
      review authors screened abstracts, applied eligibility and quality criteria and
      extracted data. Results of RCTs were pooled using a random-effects model with
      standardised mean differences (SMDs) for continuous outcomes and odds ratios
      (ORs) for binary outcomes. We assessed heterogeneity using the I(2) statistic.
      Separate meta-analyses were conducted by type of comparator: 1) minimal
      intervention such as usual practice or leaflet, 2) face-to-face intervention or
      3) a different design of ICBI; and by type of outcome (cognitive, behavioural,
      biological outcomes). MAIN RESULTS: We identified 15 RCTs of ICBI conducted in
      various settings and populations (3917 participants). Comparing ICBI to 'minimal
      interventions' such as usual practice, meta-analyses showed statistically
      significant effects as follows: moderate effect on sexual health knowledge (SMD
      0.72, 95% CI 0.27 to 1.18); small effect on safer sex self-efficacy (SMD 0.17,
      95% CI 0.05 to 0.29); small effect on safer-sex intentions (SMD 0.16, 95% CI 0.02
      to 0.30); and also an effect on sexual behaviour (OR 1.75, 95% CI 1.18 to 2.59).
      Data were insufficient for meta-analysis of biological outcomes and analysis of
      cost-effectiveness.In comparison with face-to-face sexual health interventions,
      meta-analysis was only possible for sexual health knowledge, showing that ICBI
      were more effective (SMD 0.36, 95% CI 0.13 to 0.58). Two further trials reported
      no difference in knowledge between ICBI and face-to-face intervention, but data
      were not available for pooling. There were insufficient data to analyse other
      types of outcome.No studies measured potential harms (apart from reporting any
      deterioration in measured outcomes). AUTHORS' CONCLUSIONS: ICBI are effective
      tools for learning about sexual health, and they also show positive effects on
      self-efficacy, intention and sexual behaviour. More research is needed to
      establish whether ICBI can impact on biological outcomes, to understand how
      interventions might work, and whether they are cost-effective.

PMID- 20824851
TI  - Red cell transfusion for the management of upper gastrointestinal haemorrhage.
AB  - BACKGROUND: Upper gastrointestinal haemorrhage affects 50 to 150 per 100,000
      adults per year, with a high mortality. Red blood cell transfusions are
      frequently given, but their impact on rebleeding rates and mortality is unknown.
      OBJECTIVES: To assess the effects of red blood cell (RBC) transfusion in adults
      with upper gastrointestinal haemorrhage. SEARCH STRATEGY: For this update, we re
      ran the initial search strategies from the last issue/month searched until March
      2010.We previously searched the Cochrane Upper Gastrointestinal and Pancreatic
      Diseases Group Trials Register to February 2008, the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2008, issue 1), MEDLINE (1950
      to February 2008), EMBASE (1974 to February 2008), the Systematic Review
      Initiative database of randomised controlled trials (RCTs), haematology and
      gastroenterology conference proceedings, and reference lists of articles.
      SELECTION CRITERIA: Randomised and quasi-randomised studies comparing RBC
      transfusion and standard care with other intravenous fluid and standard care
      regimens in haemodynamically stable and haemodynamically unstable adults with
      upper gastrointestinal haemorrhage. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed trial quality and extracted data. We contacted study
      authors for additional information. MAIN RESULTS: Three trials involving 126
      patients were included, with complete data available for 93 patients. The
      participants were heterogeneous, none of the three studies examined exactly the
      same interventions or measured the same outcomes. Only two trials reported
      mortality data and the summary relative risk for mortality of the intervention
      was 5.4 (95% CI 0.27 to 107.09). One trial reported increased coagulation times
      in the transfused group, and reported these patients to have increased rates of
      rebleeding. None of the studies reported adverse events directly related to RBC
      transfusion. Methodological deficiencies, including allocation concealment,
      generation of random sequences and blinding, simply compound the uncertainty
      surrounding analysis. None of the studies were appropriately powered and in the
      largest study fewer than half the participants were included in the final
      analysis.One RCT of restrictive versus liberal RBC transfusion aims to recruit
      860 patients but has yet to be completed. AUTHORS' CONCLUSIONS: There were more
      deaths and more rebleeding in the transfusion arms of the combined studies, but
      the small numbers of participants and large volume of missing data limit the
      significance of the findings. The studies in this review do not provide useful
      data regarding outcomes following red blood cell transfusion for acute upper
      gastrointestinal haemorrhage. They appear to exclude large survival benefit.
      Large, well-concealed RCTs of sufficient power are urgently needed.

PMID- 20824852
TI  - Punctal occlusion for dry eye syndrome.
AB  - BACKGROUND: Dry eye syndrome is a disorder of the tear film and is associated
      with symptoms of ocular discomfort. Punctal occlusion is a mechanical treatment
      in which the tear drainage system is blocked in order to aid in the preservation
      of natural tears on the ocular surface. OBJECTIVES: The objective of this review
      was to assess the safety and efficacy of punctal plugs for the management of dry
      eye. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled
      Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials
      Register) (The Cochrane Library 2010, Issue 6), MEDLINE (January 1950 to June
      2010), EMBASE (January 1980 to June 2010), Latin American and Caribbean
      Literature on Health Sciences (LILACS) (January 1982 to June 2010), the
      metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and
      ClinicalTrials.gov (http://clinicaltrials.gov). We also searched the Science
      Citation Index-Expanded database and reference lists of included studies. There
      were no language or date restrictions in the search for trials. The electronic
      databases were last searched on 21 June 2010. SELECTION CRITERIA: We included
      randomized and quasi-randomized controlled trials of collagen or silicone punctal
      plugs in symptomatic participants diagnosed with aqueous tear deficiency or dry
      eye syndrome. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed trial quality and extracted data. We contacted study investigators for
      additional information. MAIN RESULTS: Seven randomized controlled trials
      including 305 participants (601 eyes) met the inclusion criteria and are
      summarized in this review. We did not perform meta-analysis due to appreciable
      variability in interventions and follow-up intervals. Although punctal plugs
      provided symptomatic improvement and clinical outcomes also improved from
      baseline measures, few studies demonstrated a benefit of punctal plugs over the
      comparison intervention. Reported adverse effects included epiphora (overflow of
      tears), foreign body sensation, eye irritation, and spontaneous plug loss.
      AUTHORS' CONCLUSIONS: This systematic review shows a relative scarcity of
      controlled clinical trials assessing the efficacy of punctal occlusion therapy in
      dry eye. Although the evidence is very limited, the data suggest that silicone
      plugs can provide symptomatic relief in severe dry eye. Moreover, temporary
      collagen plugs appear similarly effective to silicone plugs on a short-term
      basis.

PMID- 20824853
TI  - Treatments for breast engorgement during lactation.
AB  - BACKGROUND: Breast engorgement is a painful and unpleasant condition affecting
      large numbers of women in the early postpartum period. During a time when mothers
      are coping with the demands of a new baby it may be particularly distressing.
      Breast engorgement may inhibit the development of successful breastfeeding, lead
      to early breastfeeding cessation, and is associated with more serious illness,
      including breast infection. OBJECTIVES: To identify the best forms of treatment
      for women who experience breast engorgement. SEARCH STRATEGY: We identified
      studies for inclusion through the Cochrane Pregnancy and Childbirth Group's
      Trials Register (February 2010). SELECTION CRITERIA: Randomised and quasi
      randomised controlled trials where treatments for breast engorgement were
      evaluated. DATA COLLECTION AND ANALYSIS: Two review authors assessed eligibility
      for inclusion and carried out data extraction. MAIN RESULTS: We included eight
      studies with 744 women. Trials examined a range of different treatments for
      breast engorgement: acupuncture (two studies), cabbage leaves (two studies), cold
      gel packs (one study), pharmacological treatments (two studies) and ultrasound
      (one study). For several interventions (ultrasound, cabbage leaves, and oxytocin)
      there was no statistically significant evidence that interventions were
      associated with a more rapid resolution of symptoms; in these studies women
      tended to have improvements in pain and other symptoms over time whether or not
      they received active treatment. There was evidence from one study that, compared
      with women receiving routine care, women receiving acupuncture had greater
      improvements in symptoms in the days following treatment, although there was no
      evidence of a difference between groups by six days, and the study did not have
      sufficient power to detect meaningful differences for other outcomes (such as
      breast abscess). A study examining protease complex reported findings favouring
      intervention groups although it is more than 40 years since the study was carried
      out, and we are not aware that this preparation is used in current practice. A
      study looking at cold packs suggested that the application of cold does not cause
      harm, and may be associated with improvements in symptoms, although differences
      between control and intervention groups at baseline mean that results are
      difficult to interpret. AUTHORS' CONCLUSIONS: Allthough some interventions may be
      promising, there is not sufficient evidence from trials on any intervention to
      justify widespread implementation. More research is needed on treatments for this
      painful and distressing condition.

PMID- 20824854
TI  - Bicarbonate versus lactate solutions for acute peritoneal dialysis.
AB  - BACKGROUND: The high mortality rate among critically ill patients with acute
      kidney injury (AKI) remains an unsolved problem in intensive care medicine,
      despite the use of renal replacement therapy (RRT). Increasing evidence from
      clinical studies in adults and children suggests that the new peritoneal dialysis
      (PD) fluids may allow for better long-term preservation of peritoneal morphology
      and function. Formation of glucose degradation products (GDPs) can be reduced and
      even avoided with the use of newer "biocompatible" solutions. However, it is
      still unclear if there are any differences in using conventional (lactate)
      solutions compared with low GDP (bicarbonate) solutions for acute PD. OBJECTIVES:
      To look at the benefits and harms of bicarbonate versus lactate solutions in
      acute PD. SEARCH STRATEGY: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE (from 1966), EMBASE (from 1980), Latin
      American and Caribbean Health Sciences Literature Database LILACS (from 1982),
      and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials
      (RCTs) comparing bicarbonate to lactate solution for acute PD. DATA COLLECTION
      AND ANALYSIS: Two authors independently assess the methodological quality of
      studies. One author abstracted data onto a standard form, and a second author
      checked data extraction. We used the random-effects model and expressed the
      results as relative risk (RR) for dichotomous outcomes and mean difference (MD)
      for continuous outcomes with 95% confidence intervals (CI). MAIN RESULTS: We
      included one study (20 patients) in this review. In shock patients, bicarbonate
      did not differ from lactate with respect to mortality (RR 0.50, 95% CI 0.06 to
      3.91); however there were significant differences in blood lactate (MD -1.60
      mmol/L, 95% CI -2.04 to -1.16), serum bicarbonate (MD 5.00 mmol/L, 95% CI 3.26 to
      6.74) and blood pH (MD 0.12, 95% CI 0.06 to 0.18). In non-shock patients there
      was a significance difference in blood lactate (MD -0.60 mmol/L, 95% CI -0.85 to 
      0.35) but not in serum bicarbonate (MD 1.10 mmol/L, 95% CI -0.27 to 2.47) or
      blood pH (MD -0.02, 95% CI -0.02 to -0.06). Other outcomes could not be analysed
      because of the limited data available. AUTHORS' CONCLUSIONS: There is no strong
      evidence that any clinical advantage for patients requiring acute PD for AKI when
      comparing conventional (lactate) with low GDP dialysis solutions (bicarbonate).

PMID- 20824855
TI  - Oestrogens for treatment or prevention of pelvic organ prolapse in postmenopausal
      women.
AB  - BACKGROUND: Pelvic organ prolapse is common and can be detected in up to 50% of
      parous women although many are asymptomatic. Oestrogen preparations are used to
      improve vaginal thinning (atrophy). It is possible that oestrogens, alone or in
      conjunction with other interventions, might prevent or assist in the management
      of pelvic organ prolapse, for example by improving the strength of weakened
      supporting structures. OBJECTIVES: To determine the effects of oestrogens or
      drugs with oestrogenic effects alone, or in conjunction with other treatments,
      both for prevention and treatment of pelvic organ prolapse. SEARCH STRATEGY: We
      searched the Cochrane Incontinence Group Specialised Register of trials (searched
      6 May 2010), MEDLINE (January 1950 to April 2010) as well as reference lists of
      relevant articles. SELECTION CRITERIA: Randomised or quasi-randomised controlled
      trials that included the use of any oestrogens or drugs with oestrogenic (or anti
      oestrogenic) actions for pelvic organ prolapse. DATA COLLECTION AND ANALYSIS:
      Trials were assessed and data extracted independently by two review authors. MAIN
      RESULTS: Three trials and one meta-analysis of adverse effects of a further three
      trials were identified. One trial did not provide useable data. Two trials
      included 148 women with prolapse, one included 58 postmenopausal women and the
      meta-analysis reported a mixed population (women with and without prolapse) of
      postmenopausal women (N=6984). The meta analysis and one other small trial
      investigated the effect of selective oestrogen receptor modulators (SERMs) for
      treatment or prevention of osteoporosis but also collected data of the effects on
      prolapse. Interventions included oestradiol, conjugated equine oestrogen and two
      (SERMs), raloxifene and tamoxifen. Only one small trial addressed the primary
      outcome (prolapse symptoms).One small treatment trial of oestradiol for three
      weeks before prolapse surgery found a reduced incidence of cystitis in the first
      four weeks after surgery but this unexpected finding needs to be confirmed in a
      larger trial.A meta-analysis of adverse effects of a SERM, raloxifene (used for
      treatment or prevention of osteoporosis in postmenopausal women) found a
      statistically significant reduction in the need for prolapse surgery at three
      year follow up (OR 0.50, 95% CI 0.31 to 0.81), but this was statistically
      significant only in women older than 60 years (OR 0.68, 95% CI 0.22 to 2.08) and
      the total number of women having prolapse surgery was small. A further small
      trial comparing conjugated equine oestrogen, raloxifene, tamoxifen and placebo in
      postmenopausal women having pelvic floor muscle training was too small to detect
      effects on prolapse outcomes. AUTHORS' CONCLUSIONS: There was limited evidence
      from randomised controlled trials regarding the use of oestrogens for the
      prevention and management of pelvic organ prolapse. The use of local oestrogen in
      conjunction with pelvic floor muscle training before surgery may reduce the
      incidence of post-operative cystitis within four weeks after surgery. Oral
      raloxifene may reduce the need for pelvic organ prolapse surgery in women older
      than 60 years although this cannot be taken as an indication for practice.There
      is a need for rigorous randomised controlled trials with long term follow up to
      assess oestrogen preparations for prevention and management of pelvic organ
      prolapse, particularly as an adjunctive treatment for women using pessaries and
      also before and after prolapse surgery.

PMID- 20824856
TI  - Internet-based interventions for smoking cessation.
AB  - BACKGROUND: The Internet has become a regular part of daily life for the majority
      of people in many parts of the world. It now offers an additional means of
      effecting changes to behaviour such as smoking. OBJECTIVES: To determine the
      effectiveness of Internet-based interventions for smoking cessation. SEARCH
      STRATEGY: We searched the Cochrane Tobacco Addiction Group Specialized Register,
      with additional searches of MEDLINE, EMBASE, CINAHL, PsycINFO, and Google
      Scholar. There were no restrictions placed on language of publication or
      publication date. The most recent search was in June 2010. SELECTION CRITERIA: We
      included randomized and quasi-randomized trials. Participants were people who
      smoked, with no exclusions based on age, gender, ethnicity, language or health
      status. Any type of Internet-based intervention was eligible. The comparison
      condition could be a no-intervention control or a different Internet site or
      programme. DATA COLLECTION AND ANALYSIS: Methodological and study quality details
      were extracted using a standardised form. We selected smoking cessation outcomes
      at short term (one to three months) and long term (6 months or more) follow up,
      and reported study effects as a risk ratio with 95% confidence intervals. Only
      limited meta-analysis was performed, as the heterogeneity of the data for
      populations, interventions and outcomes allowed for very little pooling. MAIN
      RESULTS: Twenty trials met the inclusion criteria. There were more female than
      male participants. Some Internet programmes were intensive and included multiple
      outreach contacts with participants, whilst others relied on participants to
      initiate and maintain use.Ten trials compared an Internet intervention to a non
      Internet based smoking cessation intervention or to a no intervention control.
      Six of these recruited adults, one recruited young adult university students and
      three recruited adolescents. Two trials of the same intensive automated
      intervention in populations of adult who smoked showed significantly increased
      cessation compared to printed self-help materials at 12 months. In one of these,
      all trial participants were provided with nicotine replacement therapy (NRT).
      Three other trials in adults did not detect significant long term effects. One of
      these provided access to a website as an adjunct to counselling and bupropion,
      one compared web-based counselling, proactive telephone-based counselling or a
      combination of the two as an adjunct to varenicline. The third only provided a
      list of Internet resources. One further short-term trial did show a significant
      increase in quit rates at 3 months. A trial in college students increased point
      prevalence abstinence after 30 weeks but had no effect on sustained abstinence.
      Two small trials in adolescents did not detect an effect on cessation compared to
      control, whilst a third small trial did detect a benefit of a web-based adjunct
      to a group programme amongst adolescents.Ten trials, all in adult populations,
      compared different Internet sites or programmes. There was some evidence that
      sites that were tailored and interactive might be more effective than static
      sites, but this was not detected in all the trials that explored this factor. One
      large trial did not detect differences between different Internet sites. One
      trial of a tailored intervention as an adjunct to NRT use showed a significant
      benefit but only had a 3-month follow up. One trial detected evidence of a
      benefit from tailored email letter compared to a non-tailored one. Trials failed
      to detect a benefit of including a mood management component (three trials), or
      an asynchronous bulletin board. Higher abstinence rates were typically reported
      by participants who actively engaged with the programme (as reflected by the
      number of log-ins). AUTHORS' CONCLUSIONS: Results suggest that some Internet
      based interventions can assist smoking cessation, especially if the information
      is appropriately tailored to the users and frequent automated contacts with the
      users are ensured, however trials did not show consistent effects.

PMID- 20824857
TI  - Stem cell transplantation for ischemic stroke.
AB  - BACKGROUND: Studies in animal models of ischemic stroke have shown that stem
      cells transplanted into the brain can lead to functional improvement. However, to
      date, evidence for the benefits of stem cell transplantation in ischemic stroke
      patients is lacking. OBJECTIVES: To assess the efficacy and safety of stem cell
      transplantation compared with conventional treatments in patients with ischemic
      stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register
      (last searched February 2010), the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library 2009, Issue 3), MEDLINE (1966 to August 2008),
      EMBASE (1980 to August 2008), Science Citation Index (1900 to August 2008), and
      BIOSIS (1926 to August 2008). We handsearched potentially relevant conference
      proceedings, screened reference lists, and searched ongoing trials and research
      registers (last searched November 2008). We also contacted individuals active in
      the field and stem cell manufacturers (last contacted December 2008). SELECTION
      CRITERIA: We included randomized controlled trials (RCTs) recruiting patients
      with ischemic stroke, in any phase of the disease, and an ischemic lesion
      confirmed by computerized tomography or magnetic resonance imaging scan. We
      included all types of stem cell transplantation regardless of cell source
      (autograft, allograft, or xenograft; embryonic, fetal, or adult; from brain or
      other tissues), route of cell administration (systemic or local), and dosage. The
      primary outcome was efficacy (assessed as combined functional outcome or
      disability and dependency) at longer follow-up (minimum six months). Secondary
      outcomes included post-procedure safety outcomes (death, worsening of
      neurological deficit, infections and neoplastic transformation). DATA COLLECTION
      AND ANALYSIS: Two review authors independently extracted data and assessed trial
      quality. We contacted study authors for additional information. MAIN RESULTS: We
      identified three very small RCTs. Two are still awaiting classification because
      only subgroups of patients could be included in this meta-analysis and additional
      unpublished data are needed. The third trial randomized 30 patients to
      intravenous transplantation of autologous mesenchymal stem cell (10 participants)
      or reference group (20 participants) (five participants, initially randomized to
      the intervention group, refused the treatment and were allocated to the reference
      group) and found a statistically non-significant functional improvement in
      treated patients at longer follow-up. No adverse cell-related events were
      reported. AUTHORS' CONCLUSIONS: No large trials of stem cell transplantation have
      been performed in ischemic stroke patients and it is too early to know whether
      this intervention can improve functional outcome. Large, well-designed trials are
      needed.

PMID- 20824858
TI  - Vaginal dilator therapy for women receiving pelvic radiotherapy.
AB  - BACKGROUND: Many vaginal dilator therapy guidelines advocate routine vaginal
      dilation during and after pelvic radiotherapy to prevent stenosis (abnormal
      narrowing of the vagina). The UK Gynaecological Oncology Nurse Forum recommend
      dilation "three times weekly for an indefinite time period". The UK patient
      charity Cancer Backup advises using vaginal dilators from two to eight weeks
      after the end of radiotherapy treatment. Australian guidelines recommend dilation
      after brachytherapy "as soon as is comfortably possible" and "certainly within
      four weeks and to continue for three years or indefinitely if possible". However,
      dilation is intrusive, uses health resources and can be psychologically
      distressing. It has also caused rare but very serious damage to the rectum.
      OBJECTIVES: To review the benefits and harms of vaginal dilation therapy
      associated with pelvic radiotherapy for cancer. SEARCH STRATEGY: Searches
      included the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library 2008, Issue 4), MEDLINE (1950 to 2008), EMBASE (1980 to 2008)
      and CINAHL (1982 to 2008). SELECTION CRITERIA: Any comparative randomised
      controlled trials (RCT) or data of any type which compared dilation or
      penetration of the vagina after pelvic radiotherapy treatment for cancer. DATA
      COLLECTION AND ANALYSIS: The review authors independently abstracted data and
      assessed risk of bias. We analysed the mean difference in sexual function scores
      and the risk ratio for non-compliance at six weeks and three months in single
      trial analyses. No trials met the inclusion criteria. MAIN RESULTS: Dilation
      during or immediately after radiotherapy can, in rare cases, cause damage and
      there is no persuasive evidence from any study to demonstrate that it prevents
      stenosis. Data from one RCT showed no improvement in sexual scores in women who
      were encouraged to practice dilation. Two case series and one comparative study
      using historical controls suggest that dilation might be associated with a longer
      vaginal length but these data cannot reasonably be interpreted to show that
      dilation caused the change in the vagina. AUTHORS' CONCLUSIONS: Routine dilation
      during or soon after cancer treatment may be harmful. There is no reliable
      evidence to show that routine regular vaginal dilation during or after
      radiotherapy prevents the late effects of radiotherapy or improves quality of
      life. Gentle vaginal exploration might separate the vaginal walls before they can
      stick together and some women may benefit from dilation therapy once inflammation
      has settled but there are no good comparative supporting data.

PMID- 20824860
TI  - Maintenance chemotherapy for ovarian cancer.
AB  - BACKGROUND: Epithelial ovarian cancer accounts for about 90% of all cases of
      ovarian cancer. Debulking surgery and six courses of platinum-based chemotherapy
      results in complete clinical remission (CCR) in up to 75% of cases. However, 75%
      of the responders will relapse within a median time of 18 to 28 months and only
      20% to 40% of women will survive beyond five years. It has been suggested that
      maintenance chemotherapy could assist in prolonging remission. To date, there has
      not been a systematic review on the impact of maintenance chemotherapy for
      epithelial ovarian cancer. OBJECTIVES: To assess the effectiveness and toxicity
      of maintenance chemotherapy for epithelial ovarian cancer and to evaluate the
      impact on quality of life (QoL). SEARCH STRATEGY: We searched the Cochrane
      Gynaecological Cancer Review Group Specialized Register, The Cochrane Central
      Register of Controlled Trails (CENTRAL, The Cochrane Library Issue1, 2009),
      MEDLINE, EMBASE, PubMed, CBMdisc, CNKI and VIP (to May 2009). We collected
      information from ongoing trials, checked reference lists of published articles
      and consulted experts in the field. SELECTION CRITERIA: Randomised controlled
      trials (RCTs) comparing maintenance chemotherapy with no further intervention,
      maintenance radiotherapy or other maintenance therapy. DATA COLLECTION AND
      ANALYSIS: Two review authors independently assessed trials for eligibility and
      quality and extracted data. We analysed overall survival (OS) and progression
      free survival (PFS) rates as dichotomous variables. Toxicity and QoL data were
      extracted where present. All analyses were based on intention to treat (ITT) on
      the endpoint of survival. We also analysed data by subgroups of drugs. MAIN
      RESULTS: We included six trials(902 women). When all chemotherapy regimens were
      combined, meta-analysis indicated no significant difference in 3, 5 and 10-year
      OS or PFS. For 5-year OS, the combined relative risk (RR) was 1.07 (95%
      confidence interval (CI) 0.91 to 1.27) and for the 5-year PFS the combined RR was
      1.18 (95% CI 0.88 to 1.58). Results were very similar when trials of different
      regimens were analysed. Comparing chemotherapy with radiotherapy, only the RR for
      10-year PFS in pathological complete remission was in favour of whole abdominal
      radiotherapy 0.51 (95% CI 0.27 to 1.00), while 3 and 5-year OS rates have no
      significant difference between the two groups. AUTHORS' CONCLUSIONS: There is no
      evidence to suggest that the use of platinum agents or doxorubicin used as
      maintenance chemotherapy is more effective than observation alone. Further
      investigations regarding the effect of paclitaxel used as maintenance
      chemotherapy are required.

PMID- 20824859
TI  - Parenteral opioids for maternal pain relief in labour.
AB  - BACKGROUND: Parenteral opioids are used for pain relief in labour in many
      countries throughout the world. OBJECTIVES: To assess the acceptability,
      effectiveness and safety of different types, doses and modes of administration of
      parenteral opioids given to women in labour. SEARCH STRATEGY: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (January 2010) and
      reference lists of retrieved studies. SELECTION CRITERIA: We included randomised
      controlled trials examining the use of intramuscular or intravenous opioids
      (including patient controlled analgesia) for women in labour. We looked at
      studies comparing an opioid with placebo or another opioid. DATA COLLECTION AND
      ANALYSIS: At least two review authors independently assessed study eligibility,
      collected data and assessed risk of bias. MAIN RESULTS: We included 54 studies
      involving more than 7000 women that compared an opioid with placebo or another
      opioid administered intramuscularly or intravenously. The 54 studies reported on
      27 different comparisons, and for many outcomes only one study contributed data.
      Overall the evidence was of poor quality regarding the analgesic effect of
      opioids, satisfaction with analgesia, adverse effects and harm to women and
      babies. There were few statistically significant results. Many of the studies had
      small sample sizes, and low statistical power. Overall, findings indicated that
      parenteral opioids provided some pain relief and moderate satisfaction with
      analgesia in labour, although up to two-thirds of women who received opioids
      reported moderate or severe pain and/or poor or moderate pain relief one or two
      hours after administration. Opioid drugs were associated with maternal nausea,
      vomiting and drowsiness, although different opioid drugs were associated with
      different adverse effects. There was no clear evidence of adverse effects of
      opioids on the newborn. We did not have sufficient evidence to assess which
      opioid drug provided the best pain relief with the least adverse effects.
      AUTHORS' CONCLUSIONS: Parenteral opioids provide some relief from pain in labour
      but are associated with adverse effects. Maternal satisfaction with opioid
      analgesia was largely unreported but appeared moderate at best. We did not
      examine the effectiveness and safety of parenteral opioids compared with other
      methods of pain relief in labour and this review needs to be examined alongside
      related Cochrane reviews. More research is needed to determine which analgesic
      intervention is most effective, and provides greatest satisfaction to women with
      acceptable adverse events for mothers and their newborns.

PMID- 20824861
TI  - Stretch for the treatment and prevention of contractures.
AB  - BACKGROUND: Contractures are a common complication of neurological and
      musculoskeletal conditions, and are characterised by a reduction in joint
      mobility. Stretch is widely used for the treatment and prevention of
      contractures. However, it is not clear whether stretch is effective. OBJECTIVES:
      To determine the effects of stretch on contractures in people with, or at risk
      of, contractures. SEARCH STRATEGY: Electronic searches were conducted on CENTRAL,
      DARE, HTA (The Cochrane Library); MEDLINE; CINAHL; EMBASE; SCI-EXPANDED; and
      PEDro (April 2009). SELECTION CRITERIA: Randomised controlled trials and
      controlled clinical trials of stretch applied for the purpose of treating or
      preventing contractures were included. DATA COLLECTION AND ANALYSIS: Two review
      authors independently selected trials, extracted data, and assessed risk of bias.
      The primary outcomes of interest were joint mobility and quality of life. The
      secondary outcomes were pain, spasticity, activity limitation and participation
      restriction. Outcomes were evaluated immediately after intervention, in the short
      term (one to seven days) and in the long term (> one week). Effects were
      expressed as mean differences or standardised mean differences with 95%
      confidence intervals (CI). Meta-analyses were conducted with a random-effects
      model. MAIN RESULTS: Thirty-five studies with 1391 participants met the inclusion
      criteria. No study performed stretch for more than seven months. In people with
      neurological conditions, there was moderate to high quality evidence to indicate
      that stretch does not have clinically important immediate (mean difference 3
      degrees ; 95% CI 0 to 7), short-term (mean difference 1 degrees ; 95% CI 0 to 3)
      or long-term (mean difference 0 degrees ; 95% CI -2 to 2) effects on joint
      mobility. The results were similar for people with non-neurological conditions.
      For all conditions, there is little or no effect of stretch on pain, spasticity,
      activity limitation, participation restriction or quality of life. AUTHORS'
      CONCLUSIONS: Stretch does not have clinically important effects on joint mobility
      in people with, or at risk of, contractures if performed for less than seven
      months. The effects of stretch performed for periods longer than seven months
      have not been investigated.

PMID- 20824862
TI  - Chinese herbal medicine for subfertile women with polycystic ovarian syndrome.
AB  - BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common
      reproductive endocrinology abnormalities, affecting 5% to 10% of women of
      reproductive age. Western medicines, such as oral contraceptives and insulin
      sensitizers, have been widely used to improve the symptoms and signs for PCOS.
      Recently, many studies have been published considering Chinese herbal medicine
      (CHM) as an alternative treatment for women with PCOS. OBJECTIVES: To evaluate
      the efficacy and safety of Chinese medicinal herbs for subfertile women with
      PCOS. SEARCH STRATEGY: We searched the following databases (from inception to
      March 2010): Menstrual Disorders and Subfertility Group Specialised Register
      (MDSG), Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE,
      EMBASE, Allied and Complementary Medicine (AMED), PsycINFO, Chinese National
      Knowledge Infrastructure (CNKI), VIP, Wanfang. In addition, all reference lists
      of included trials were searched and experts in the field were contacted to
      locate trials. SELECTION CRITERIA: Randomized controlled trials (RCT) considering
      the use of CHM for the treatment of subfertile women with PCOS. DATA COLLECTION
      AND ANALYSIS: Two review authors independently screened appropriate trials for
      inclusion, assessed methodological quality, and extracted data. We contacted
      primary authors for additional information. Meta-analysis was conducted. Odds
      ratio (OR) was used for reporting dichotomous data with 95% confidence intervals
      (CI). MAIN RESULTS: Four RCTs involving 344 participants were included. The
      methodological risk of bias of included studies was poor. Different interventions
      were used in these four RCTs.There was evidence of statistically significant
      difference seen improving pregnancy rate (per woman) between CHM plus clomiphene
      and clomiphene (OR 2.97, 95%CI 1.71 to 5.17). However, there was no statistically
      significant difference seen in the other comparison groups for improving
      pregnancy rate (per woman).There was no evidence of statistically significant
      difference in improving ovulation rate (per woman) between CHM and clomiphene (OR
      1.42, 95%CI 0.19 to 10.49), between CHM plus laparoscopic ovarian drilling (LOD)
      and LOD (OR 2.43, 95%CI 0.39 to 15.08).There were not statistically significant
      difference between CHM plus follicle aspiration, ovulation induction and follicle
      aspiration plus ovulation induction for adverse events including LUFS, OHSS and
      multiple pregnancy.Live birth rate was not reported by any studies. AUTHORS'
      CONCLUSIONS: There is limited evidence that the addition of CHM to clomiphene is
      associated with improved clinical pregnancy outcomes and no other evidence of any
      other effect. The methodology of RCTs was not adequately reported by primary
      studies.

PMID- 20824864
TI  - Interventions for the treatment of borderline ovarian tumours.
AB  - BACKGROUND: The safety of conservative surgery and the benefit of additional
      interventions after surgery for borderline ovarian tumours are unknown.
      OBJECTIVES: To evaluate the benefits and harm of different treatment modalities
      offered for borderline ovarian tumours. SEARCH STRATEGY: We searched the Cochrane
      Gynaecological Cancer Group Trials Register to 2009, Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 4), MEDLINE and
      EMBASE to 2009. We also searched registers of clinical trials, abstracts of
      scientific meetings, reference lists of included studies. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) that compared different interventions in
      adult women diagnosed with borderline ovarian tumours of any histological
      variant. DATA COLLECTION AND ANALYSIS: Two review authors independently
      abstracted data and assessed risk of bias. MAIN RESULTS: We identified seven RCTs
      that enrolled 372 women. We could not pool results of trials as the treatment
      comparisons differed.Six RCTs (n = 340) conducted over 15 years ago, evaluated
      adjuvant therapy (chemotherapy, pelvic external irradiation or intra-peritoneal
      radioactive isotope therapy) after radical surgery; over 87% of participants had
      Stage I tumours. Most participants were followed up for over 10 years. Overall
      and recurrence-free survival were similar between both arms of these trials,
      except that one trial (n = 66) showed a significantly lower survival (P = 0.03)
      in women who received chemotherapy (thio-TEPA). Adverse effects of treatment were
      incompletely reported and all six trials were at high risk of bias.One further
      trial (n = 32) that recruited participants with bilateral serous tumours who were
      wishing fertility preservation, revealed a significantly increased chance of
      pregnancy (hazard ratio (HR) = 3.3, 95% CI 1.4 to 8.0) but non-significantly
      earlier disease recurrence (HR = 1.5, 95% CI 0.6 to 3.8) in the women who had
      ultra-conservative surgery (bilateral cystectomy) than in those who had
      conservative surgery (cystectomy and contralateral oophorectomy). This trial was
      at low risk of bias.Quality of life (QoL) was not documented in any included
      trial. We did not find any trials that compared radical with conservative surgery
      or laparoscopy with laparotomy. AUTHORS' CONCLUSIONS: We did not find evidence to
      support the use of any specific type of adjuvant therapy for borderline ovarian
      tumours. RCTs evaluating the benefit of adjuvant therapy with optimally dosed
      chemotherapy and newer targeted drugs are necessary, particularly for advanced
      borderline ovarian tumours. The low mortality from borderline ovarian tumours
      should make recurrence-free survival, time to recurrence and morbidity important
      end points in such trials.Bilateral cystectomy may be offered to women with
      bilateral borderline ovarian tumours diagnosed intra-operatively who are wishing
      to preserve their fertility. Similarly, women who had RCTs comparing radical with
      conservative surgery and comparing laparoscopy with laparotomy are needed.

PMID- 20824863
TI  - Interventions for nausea and vomiting in early pregnancy.
AB  - BACKGROUND: Nausea, retching and vomiting are very commonly experienced by women
      in early pregnancy. There are considerable physical and psychological effects on
      women who experience these symptoms. This is an update of a review of
      interventions for nausea and vomiting in early pregnancy previously published in
      2003. OBJECTIVES: To assess the effectiveness and safety of all interventions for
      nausea, vomiting and retching in early pregnancy, up to 20 weeks' gestation.
      SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (28 May 2010). SELECTION CRITERIA: All randomised controlled trials of
      any intervention for nausea, vomiting and retching in early pregnancy. We
      excluded trials of interventions for hyperemesis gravidarum which are covered by
      another review. We also excluded quasi-randomised trials and trials using a
      crossover design. DATA COLLECTION AND ANALYSIS: Four review authors, in pairs,
      reviewed the eligibility of trials and independently evaluated the risk of bias
      and extracted the data for included trials. MAIN RESULTS: Twenty-seven trials,
      with 4041 women, met the inclusion criteria. These trials covered many
      interventions, including acupressure, acustimulation, acupuncture, ginger,
      vitamin B6 and several antiemetic drugs. We identified no studies of dietary or
      other lifestyle interventions. Evidence regarding the effectiveness of P6
      acupressure, auricular (ear) acupressure and acustimulation of the P6 point was
      limited. Acupuncture (P6 or traditional) showed no significant benefit to women
      in pregnancy. The use of ginger products may be helpful to women, but the
      evidence of effectiveness was limited and not consistent. There was only limited
      evidence from trials to support the use of pharmacological agents including
      vitamin B6, and anti-emetic drugs to relieve mild or moderate nausea and
      vomiting. There was little information on maternal and fetal adverse outcomes and
      on psychological, social or economic outcomes. We were unable to pool findings
      from studies for most outcomes due to heterogeneity in study participants,
      interventions, comparison groups, and outcomes measured or reported. The
      methodological quality of the included studies was mixed. AUTHORS' CONCLUSIONS:
      Given the high prevalence of nausea and vomiting in early pregnancy, health
      professionals need to provide clear guidance to women, based on systematically
      reviewed evidence. There is a lack of high-quality evidence to support that
      advice. The difficulties in interpreting the results of the studies included in
      this review highlight the need for specific, consistent and clearly justified
      outcomes and approaches to measurement in research studies.

PMID- 20824865
TI  - Interventions for acute internal hordeolum.
AB  - BACKGROUND: Hordeolum is a common, painful, inflammation of the eyelid margin
      that is usually caused by bacterial infection. The infection affects oil glands
      of the eyelid and can be internal or external. In many cases, the lesion drains
      spontaneously and resolves untreated; however, the inflammation can spread to
      other ocular glands or tissues and recurrences are common. If unresolved, acute
      internal hordeolum can become chronic or develop into a chalazion. External
      hordeola, also known as styes, were not included in the scope of this review.
      OBJECTIVES: The objective of this review was to investigate the effectiveness and
      safety of non-surgical treatments for acute internal hordeolum compared to
      observation or placebo. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and
      Vision Group Trials Register) (The Cochrane Library 2010, Issue 6), MEDLINE
      (January 1950 to June 2010), EMBASE (January 1980 to June 2010), Latin American
      and Caribbean Literature on Health Sciences (LILACS) (January 1982 to June 2010),
      the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com),
      ClinicalTrials.gov (http://clinicaltrials.gov) and the WHO International Clinical
      Trials Registry Platform (ICTRP). There were no language or date restrictions in
      the search for trials. The electronic databases were last searched on 21 June
      2010. SELECTION CRITERIA: The selection criteria for this review included
      randomized or quasi-randomized clinical trials of patients diagnosed with acute
      internal hordeolum. Studies of patients with external hordeolum (stye), chronic
      hordeolum or chalazion were excluded. Non-surgical interventions of interest
      included the use of hot or warm compresses, lid scrubs, antibiotics, or steroids
      compared to observation, placebo, or other active interventions. DATA COLLECTION
      AND ANALYSIS: Two review authors independently assessed the references identified
      by the electronic searches for inclusion in this review. No relevant studies were
      found. The reasons for exclusion were documented. MAIN RESULTS: There were no
      trials identified for inclusion in this review. The majority of the references
      identified from our search reported on external hordeola or chronic internal
      hordeola. The few references specific to acute internal hordeolum reported mostly
      recommendations for treatment or were reports of interventional case series, case
      studies, or other types of observational study designs and were published over 20
      years ago. AUTHORS' CONCLUSIONS: We did not find any evidence for or against the
      effectiveness of non-surgical interventions for the treatment of hordeolum.
      Controlled clinical trials would be useful in determining which interventions are
      effective for the treatment of acute internal hordeolum.

PMID- 20824866
TI  - Antiemetic medication for prevention and treatment of chemotherapy induced nausea
      and vomiting in childhood.
AB  - BACKGROUND: Nausea and vomiting are still a problem for children undergoing
      treatment for malignancies despite new antiemetic therapies. Optimising
      antiemetic regimens could improve quality of life by reducing nausea, vomiting
      and associated clinical problems. OBJECTIVES: To assess the effectiveness and
      adverse events of pharmacological interventions in controlling anticipatory,
      acute and delayed nausea and vomiting in children and young people (aged < 18
      years) about to receive/receiving chemotherapy. SEARCH STRATEGY: Searches
      included CENTRAL, MEDLINE, EMBASE and LILACS, trial registries from their
      earliest records to February 2008, and ASCO, MASCC and SIOP conference
      proceedings from 2001 to 2007. We examined references of systematic reviews and
      contacted trialists for information on further studies. SELECTION CRITERIA: Two
      authors independently screened abstracts to identify randomised controlled trials
      (RCTs) that compared a pharmacological antiemetic, cannabinoid or benzodiazepine
      with placebo or any alternative active intervention in children and young people
      (< 18 years) with a diagnosis of cancer who were to receive chemotherapy. DATA
      COLLECTION AND ANALYSIS: Two authors independently extracted outcome and quality
      data from each RCT. When appropriate, we undertook meta-analysis. MAIN RESULTS:
      We included 28 studies which examined a range of different antiemetics, used
      different doses and comparators, and reported a variety of outcomes. The quality
      and quantity of included studies limited the exploration of heterogeneity to
      narrative approaches only.The majority of quantitative data related to the
      complete control of acute vomiting (22 studies). Adverse events were reported in
      24 studies and nausea outcomes in 10 studies.The addition of dexamethasone to 5
      HT(3) antagonists was assessed in two studies for complete control of vomiting
      (pooled relative risk (RR) 2.03; 95% CI 1.35 to 3.04). Three studies compared
      granisetron 20 mcg/kg with 40 mcg/kg for complete control of vomiting (pooled RR
      0.93; 95% CI 0.80 to 1.07). No other pooled analyses were possible.Narrative
      synthesis suggests 5-HT(3) antagonists are more effective than older antiemetic
      agents even when combined with a steroid. Cannabinoids are probably effective but
      produce frequent side effects. AUTHORS' CONCLUSIONS: Our overall knowledge of the
      most effective antiemetics to prevent chemotherapy-induced nausea and vomiting in
      childhood is incomplete. Future research should be undertaken in consultation
      with children, young people and families that have experienced chemotherapy and
      should make use of validated, age-appropriate measures. This review suggests that
      5-HT(3) antagonists with dexamethasone added are effective in patients who are to
      receive highly emetogenic chemotherapy although the risk-benefit profile of
      additional steroid remains uncertain.

PMID- 20824867
TI  - Interventions for treating osteoarthritis of the big toe joint.
AB  - BACKGROUND: Osteoarthritis affecting of the big toe joint of the foot (hallux
      limitus or rigidus) is a common and painful condition. Although several
      treatments have been proposed, few have been adequately evaluated. OBJECTIVES: To
      identify controlled trials evaluating interventions for osteoarthritis of the big
      toe joint and to determine the optimum intervention(s). SEARCH STRATEGY:
      Literature searches were conducted across the following electronic databases:
      CENTRAL; MEDLINE; EMBASE; CINAHL; and PEDro (to 14th January 2010). No language
      restrictions were applied. SELECTION CRITERIA: Randomised controlled trials,
      quasi-randomised trials, or controlled clinical trials that assessed treatment
      outcomes for osteoarthritis of the big toe joint. Participants of any age or
      gender with osteoarthritis of the big toe joint (defined either radiographically
      or clinically) were included. DATA COLLECTION AND ANALYSIS: Two authors examined
      the list of titles and abstracts identified by the literature searches. One
      content area expert and one methodologist independently applied the pre
      determined inclusion and exclusion criteria to the full text of identified
      trials. To minimise error and reduce potential bias, data were extracted
      independently by two content experts. MAIN RESULTS: Only one trial satisfactorily
      fulfilled the inclusion criteria and was included in this review. This trial
      evaluated the effectiveness of two physical therapy programs in 20 individuals
      with osteoarthritis of the big toe joint. Assessment outcomes included pain
      levels, big toe joint range of motion and plantar flexion strength of the hallux.
      Mean differences at four weeks follow up were 3.80 points (95% CI 2.74 to 4.86)
      for self reported pain, 28.30 degrees (95% CI 21.37 to 35.23) for big toe joint
      range of motion, and 2.80 kg (95% CI 2.13 to 3.47) for muscle strength. Although
      differences in outcomes between treatment and control groups were reported, the
      risk of bias was high. The trial failed to employ appropriate randomisation or
      adequate allocation concealment, used a relatively small sample and incorporated
      a short follow up (four weeks). No adverse reactions were reported. AUTHORS'
      CONCLUSIONS: The reviewed trial presented a high risk of bias, which limited
      conclusions that could be drawn from the presented data. The inclusion of only
      one trial indicates the need for more robust randomised controlled trials to
      determine the efficacy of interventions for this condition.

PMID- 20824868
TI  - Different antibiotic regimens for treating asymptomatic bacteriuria in pregnancy.
AB  - BACKGROUND: Asymptomatic bacteriuria occurs in 5% to 10% of pregnancies and, if
      left untreated, can lead to serious complications. OBJECTIVES: To assess which
      antibiotic is most effective and least harmful as initial treatment for
      asymptomatic bacteriuria in pregnancy. SEARCH STRATEGY: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (March 2010) and reference lists
      of retrieved studies. SELECTION CRITERIA: Randomized controlled trials comparing
      two antibiotic regimens for treating asymptomatic bacteriuria. DATA COLLECTION
      AND ANALYSIS: Review authors independently screened the studies for inclusion and
      extracted data. MAIN RESULTS: We included five studies involving 1140 women with
      asymptomatic bacteriuria. We did not perform meta-analysis; each trial examined
      different antibiotic regimens and so we were not able to pool results. In a study
      comparing a single dose of fosfomycin trometamol 3 g with a five-day course of
      cefuroxime, there was no significant difference in persistent infection (risk
      ratio (RR) 1.36, 95% confidence interval (CI) 0.24 to 7.75), shift to other
      antibiotics (RR 0.08, 95% CI 0.00 to 1.45), or in allergy or pruritus (RR 2.73,
      95% CI 0.11 to 65.24). A comparison of seven-day courses of 400 mg pivmecillinam
      versus 500 mg ampicillin, both given four times daily, showed no significant
      difference in persistent infection at two weeks or recurrent infection, but there
      was an increase in vomiting (RR 4.57, 95% CI 1.40 to 14.90) and women were more
      likely to stop treatment early with pivmecillinam (RR 8.82, 95% CI 1.16 to
      66.95). When cephalexin 1 g versus Miraxid(R) (pivmecillinam 200 mg and
      pivampicillin 250 mg) were given twice-daily for three days, there was no
      significant difference in persistent or recurrent infection. A one- versus seven
      day course of nitrofurantoin resulted in more persistent infection with the
      shorter course (RR 1.76, 95% CI 1.29 to 2.40), but no significant difference in
      symptomatic infection at two weeks, nausea, or preterm birth. Comparing
      cycloserine with sulphadimidine, no significant differences in symptomatic,
      persistent, or recurrent infections were noted. AUTHORS' CONCLUSIONS: We cannot
      draw any definite conclusion on the most effective and safest antibiotic regimen
      for the initial treatment of asymptomatic bacteriuria in pregnancy. One study
      showed advantages with a longer course of nitrofurantoin, and another showed
      better tolerability with ampicillin compared with pivmecillinam; otherwise, there
      was no significant difference demonstrated between groups treated with different
      antibiotics. Given this lack of conclusive evidence, it may be useful for
      clinicians to consider factors such as cost, local availability and side effects
      in the selection of the best treatment option.

PMID- 20824869
TI  - Cervical pessary for preventing preterm birth.
AB  - BACKGROUND: Preterm delivery is a major health problem and contributes to more
      than 50% of the overall perinatal mortality. Cervical incompetence is one of the
      common causes of preterm birth to which different management strategies have been
      tried including cervical cerclage. Cervical cerclage is an invasive technique
      that needs anaesthesia and may be associated with complications. Moreover, there
      is still a matter of controversy regarding the efficacy and the group of patients
      which could benefit from this operation. Cervical pessary has been tried as a
      simple, non-invasive alternative that might replace the above invasive cervical
      stitch operation. OBJECTIVES: To evaluate the efficacy of cervical pessary for
      prevention of preterm birth in women with cervical incompetence. SEARCH STRATEGY:
      We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (May
      2010), Current Controlled Trials and the Australian New Zealand Clinical Trials
      Registry (May 2010). SELECTION CRITERIA: We selected all published and
      unpublished randomised clinical trials comparing the use of cervical pessary with
      cervical cerclage or expectant management for prevention of preterm birth. We did
      not include quasi-randomised trials, cluster-randomised and crossover trials.
      DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials
      for inclusion. MAIN RESULTS: The search identified two trials which we excluded.
      Three additional trials are ongoing. This review contains no included studies.
      AUTHORS' CONCLUSIONS: The review did not identify any well-designed randomised
      clinical trial in order to confirm or refute the benefit of cervical pessary.
      However, there is evidence from non-randomised trials that showed some benefit of
      cervical pessary in preventing preterm birth. We are waiting for the results of
      three ongoing randomised controlled trials, assessing the role of cervical
      pessary in women with short cervix. There is a need for further well-designed
      randomised controlled trials.

PMID- 20824870
TI  - Interventions for cough in cancer.
AB  - BACKGROUND: Cough is a common symptom in patients with malignancies, especially
      in patients with lung cancer. Cough is not well controlled in clinical practice
      and clinicians have few management options to treat it. OBJECTIVES: The primary
      objective of this review was to determine the effectiveness of interventions,
      both pharmacological and non-pharmacological, (other than chemotherapy and
      external beam radiotherapy) in the management of cough in malignant disease
      (especially in lung cancer). SEARCH STRATEGY: Databases searched included: The
      Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of
      Abstracts of Reviews of Effectiveness (DARE) (The Cochrane Library issue 4,
      2009); MEDLINE (1966 to May 2010); EMBASE (1980 to May 2010); CINAHL (1980 to May
      2010); PSYCHINFO (1980 to May 2010); AMED (1985 to May 2010); SIGLE (1980 to May
      2010); British Nursing Index (1985 to May 2010); CancerLit (1975 to May 2010). We
      searched for cough suppressants, antitussives and other drugs with antitussive
      activity as well as non-pharmacological interventions (see Appendices 1-4 for
      search terms). SELECTION CRITERIA: We selected randomised controlled trials
      (RCTs) and clinical trials (quasi-experimental trials, and trials where there is
      a comparison group but no mention of randomisation) in participants with primary
      or metastatic lung cancer or other cancers. DATA COLLECTION AND ANALYSIS: Two
      review authors independently assessed titles and abstracts of all studies, and
      extracted data from all selected studies before reaching consensus. A third
      review author arbitrated with any disagreement. Meta-analysis was not attempted
      due to the heterogeneity of studies. MAIN RESULTS: Seventeen studies met
      inclusion criteria and examined either brachytherapy, laser or photodynamic
      therapy (eight studies) or a variety of pharmacological therapies (nine studies).
      Overall, there was absence of credible evidence and the majority of studies were
      of low methodological quality and high risk of bias. Brachytherapy seemed to
      improve cough in a variety of doses in selected participants, suggesting that
      possibly the lowest effective dose should be used to minimise side effects.
      Photodynamic therapy was examined in one study, and while improvements in cough
      were observed, its role over other therapies for cough is unclear. Some
      indication of effect was observed with morphine, codeine, dihydrocodeine,
      levodropropizine, sodium cromoglycate and butamirate citrate linctus (cough
      syrup), although all studies had significant risk of bias. AUTHORS' CONCLUSIONS:
      No practice recommendations could be drawn from this review. There is an urgent
      need to increase the number and quality of studies evaluating the effects of
      interventions in the management of cough in cancer.

PMID- 20824871
TI  - Positive end-expiratory pressure (PEEP) during anaesthesia for the prevention of
      mortality and postoperative pulmonary complications.
AB  - BACKGROUND: General anaesthesia causes atelectasis which can lead to impaired
      respiratory function. Positive end-expiratory pressure (PEEP) is a mechanical
      manoeuvre which increases functional residual capacity (FRC) and prevents
      collapse of the airways thereby reducing atelectasis. It is not known whether
      intra-operative PEEP alters the risk of postoperative mortality and pulmonary
      complications. OBJECTIVES: To assess the benefits and harms of intraoperative
      PEEP, for all adult surgical patients, on postoperative mortality and pulmonary
      outcomes. SEARCH STRATEGY: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 4), MEDLINE (via
      Ovid) (1966 to January 2010), EMBASE (via Ovid) (1980 to January 2010), CINAHL
      (via EBSCOhost) (1982 to January 2010), ISI Web of Science (1945 to January 2010)
      and LILACS (via BIREME interface) (1982 to January 2010). SELECTION CRITERIA: We
      included randomized clinical trials that evaluated the effect of PEEP versus no
      PEEP, during general anaesthesia, on postoperative mortality and postoperative
      respiratory complications. We included studies irrespective of language and
      publication status. DATA COLLECTION AND ANALYSIS: Two investigators independently
      selected papers, extracted data that fulfilled our outcome criteria and assessed
      the quality of all included trials. We undertook pooled analyses, where
      appropriate. For our primary outcome (mortality) and two secondary outcomes
      (respiratory failure and pneumonia), we calculated the number of further patients
      needed (information size) in order to make reliable conclusions. MAIN RESULTS: We
      included eight randomized trials with a total of 330 patients. Two trials had a
      low risk of bias. There was no difference demonstrated for mortality (relative
      risk (RR) 0.95, 95% CI 0.14 to 6.39). Two statistically significant results were
      found: the PEEP group had a higher PaO(2)/FiO(2) on day 1 postoperatively (mean
      difference (MD) 22.98, 95% CI 4.40 to 41.55) and postoperative atelectasis
      (defined as an area of collapsed lung, quantified by computerized tomography (CT)
      scan) was less in the PEEP group (SMD -1.2, 95% CI -1.78 to -0.79). There were no
      adverse events reported in the three trials that adequately measured these
      outcomes (barotrauma and cardiac complications). Using information size
      calculations, we estimated that a further 21,200 patients would need to be
      randomized in order to make a reliable conclusion about PEEP and mortality.
      AUTHORS' CONCLUSIONS: There is currently insufficient evidence to make
      conclusions about whether intraoperative PEEP alters the risk of postoperative
      mortality and respiratory complications among undifferentiated surgical patients.

PMID- 20824872
TI  - Corticosteroids for HELLP (hemolysis, elevated liver enzymes, low platelets)
      syndrome in pregnancy.
AB  - BACKGROUND: Pre-eclampsia is a relatively common complication of pregnancy. HELLP
      (hemolysis, elevated liver enzymes, low platelets) syndrome is a severe
      manifestation of pre-eclampsia with significant morbidity and mortality for
      pregnant women and their children. Corticosteroids are commonly used in the
      treatment of HELLP syndrome in the belief that they improve outcomes. OBJECTIVES:
      To determine the effects of corticosteroids on women with HELLP syndrome and
      their children. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (30 June 2010). SELECTION CRITERIA: Randomized
      controlled trials comparing any corticosteroid with placebo, no treatment, or
      other drug; or comparing one corticosteroid with another corticosteroid or dosage
      in women with HELLP syndrome. DATA COLLECTION AND ANALYSIS: Two review authors
      assessed trial quality and extracted data independently. MAIN RESULTS: Eleven
      trials (550 women) compared corticosteroids with placebo or no treatment. There
      was no difference in the risk of maternal death (risk ratio (RR) 0.95, 95%
      confidence interval (CI) 0.28 to 3.21), maternal death or severe maternal
      morbidity (RR 0.27, 95% CI 0.03 to 2.12), or perinatal/infant death (RR 0.64, 95%
      CI 0.21 to 1.97). The only clear effect of treatment on individual outcomes was
      improved platelet count (standardized mean difference (SMD) 0.67, 95% CI 0.24 to
      1.10). The effect on platelet count was strongest for women who commenced
      treatment antenatally (SMD 0.80, 95% CI 0.25 to 1.35).Two trials (76 women)
      compared dexamethasone with betamethasone. There was no clear evidence of a
      difference between groups in respect to perinatal/infant death (RR 0.95, 95% CI
      0.15 to 6.17) or severe perinatal/infant morbidity or death (RR 0.64, 95% CI 0.27
      to 1.48). Maternal death and severe maternal morbidity were not reported. In
      respect to platelet count, dexamethasone was superior to betamethasone (MD 6.02,
      95% CI 1.71 to 10.33), both when treatment was commenced antenatally (MD 8.10,
      95% CI 6.23 to 9.97) and postnatally (MD 3.70, 95% CI 0.96 to 6.44). AUTHORS'
      CONCLUSIONS: There was no clear evidence of any effect of corticosteroids on
      substantive clinical outcomes. Those receiving steroids showed significantly
      greater improvement in platelet counts which was greater for those receiving
      dexamethasone than those receiving betamethasone. There is to date insufficient
      evidence of benefits in terms of substantive clinical outcomes to support the
      routine use of steroids for the management of HELLP. The use of corticosteroids
      may be justified in clinical situations in which increased rate of recovery in
      platelet count is considered clinically worthwhile.

PMID- 20824873
TI  - Non-invasive brain stimulation techniques for chronic pain.
AB  - BACKGROUND: Non-invasive brain stimulation techniques aim to induce an electrical
      stimulation of the brain in an attempt to reduce chronic pain by directly
      altering brain activity. They include repetitive transcranial magnetic
      stimulation (rTMS), cranial electrotherapy stimulation (CES) and transcranial
      direct current stimulation (tDCS). OBJECTIVES: To evaluate the efficacy of non
      invasive brain stimulation techniques in chronic pain. SEARCH STRATEGY: We
      searched CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, the Cochrane PaPaS
      Group Trials Register and clinical trials registers. SELECTION CRITERIA:
      Randomised and quasi-randomised studies of rTMS, CES or tDCS if they employed a
      sham stimulation control group, recruited patients over the age of 18 with pain
      of three months duration or more and measured pain as a primary outcome. DATA
      COLLECTION AND ANALYSIS: Two authors independently extracted and verified data.
      Where possible we entered data into meta-analyses. We excluded studies judged as
      being at high risk of bias from the analysis. MAIN RESULTS: We included 33 trials
      in the review (involving 937 people)(19 rTMS, eight CES and six tDCS). Only one
      study was judged as being at low risk of bias.Studies of rTMS (involving 368
      participants ) demonstrated significant heterogeneity. Pre-specified subgroup
      analyses suggest that low-frequency stimulation is ineffective. A short-term
      effect on pain of active high-frequency stimulation of the motor cortex in single
      dose studies was suggested (standardised mean difference (SMD) -0.40, 95%
      confidence interval (CI) -0.26 to -0.54, P < 0.00001). This equates to a 15% (95%
      CI 10% to 20%) reduction in pain which does not clearly exceed the pre
      established criteria for a minimally clinically important difference (> 15%).For
      CES (four studies, 133 participants) no statistically significant difference was
      found between active stimulation and sham. Analysis of tDCS studies (five
      studies, 83 people) demonstrated significant heterogeneity and did not find a
      significant difference between active and sham stimulation. Pre-specified
      subgroup analysis of tDCS applied to the motor cortex suggested superiority of
      active stimulation over sham (SMD -0.59, 95% CI -1.10 to -0.08).Non-invasive
      brain stimulation appears to be associated with minor and transient side effects.
      AUTHORS' CONCLUSIONS: Single doses of high-frequency rTMS of the motor cortex may
      have small short-term effects on chronic pain. The effects do not clearly exceed
      the predetermined threshold of minimal clinical significance. Low-frequency rTMS
      is not effective in the treatment of chronic pain. There is insufficient evidence
      from which to draw firm conclusions regarding the efficacy of CES or tDCS. The
      available evidence suggests that tDCS applied to the motor cortex may have short
      term effects on chronic pain and that CES may be ineffective. There is a need for
      further, rigorously designed studies of all types of stimulation.

PMID- 20824874
TI  - Botulinum toxin for shoulder pain.
AB  - BACKGROUND: Recent evidence suggests an anti-nociceptive effect of botulinum
      toxin. OBJECTIVES: To compare the efficacy and safety of botulinum toxin in
      comparison to placebo or other treatment options for shoulder pain. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library), Ovid MEDLINE, CINAHL (via EBSCOhost), Ovid
      SPORTDiscus, EMBASE and Science Citation Index. SELECTION CRITERIA: Randomized
      controlled trials (RCTs) comparing botulinum toxin with placebo or active
      treatment in people with shoulder pain were included. DATA COLLECTION AND
      ANALYSIS: For continuous measures we calculated mean difference (MD), and for
      categorical measures risk ratio (RR) (with 95% confidence interval (CI)). MAIN
      RESULTS: Six RCTs with 164 patients were included. Five RCTs in participants with
      post-stroke shoulder pain indicated that compared with placebo, a single
      intramuscular injection of botulinum toxin A significantly reduced pain at three
      to six months post-injection (MD -1.2 points, 95% CI -2.4 to -0.07; 0 to 10 point
      scale) but not at one month (MD -1.1 points, 95% CI -2.9 to 0.7). Shoulder
      external rotation was increased at one month (MD 9.8 degrees , 95% CI 0.2 to
      19.4) but not at three to six months. Shoulder abduction, external rotation or
      spasticity did not differ between groups, nor did the number of adverse events
      (RR 1.46, 95% CI 0.6 to 24.3).One RCT in arthritis-related shoulder pain
      indicated that botulinum toxin reduced pain severity (MD -2.0, 95% CI -3.7 to 
      0.3; 10 point scale) and shoulder disability with a reduction in Shoulder Pain
      and Disability Index score (MD -13.4, 95% CI -24.9 to -1.9; 100 point scale) when
      compared with placebo. Shoulder abduction was improved (MD 13.8 degrees, 95% CI
      3.2 to 44.0). Serious adverse events did not differ between groups (RR 0.35, 95%
      CI: 0.11, 1.12). AUTHORS' CONCLUSIONS: The results should be interpreted with
      caution due to few studies with small sample sizes and high risk of bias.
      Botulinum toxin A injections seem to reduce pain severity and improve shoulder
      function and range of motion when compared with placebo in patients with shoulder
      pain due to spastic hemiplegia or arthritis. It is unclear if the benefit of pain
      relief in post-stroke shoulder pain at three to six months but not at one month
      is due to limitations of the evidence, which includes small sample sizes with
      imprecise estimates, or a delayed onset of action. More studies with safety data
      are needed.

PMID- 20824875
TI  - Utero-placental Doppler ultrasound for improving pregnancy outcome.
AB  - BACKGROUND: Impaired placentation can cause some of the most important
      obstetrical complications such as pre-eclampsia and intrauterine growth
      restriction and has been linked to increased fetal morbidity and mortality. The
      failure to undergo physiological trophoblastic vascular changes is reflected by
      the high impedance to the blood flow at the level of the uterine arteries.
      Doppler ultrasound study of utero-placental blood vessels, using waveform indices
      or notching, may help to identify the 'at-risk' women in the first and second
      trimester of pregnancy, such that interventions might be used to reduce maternal
      and fetal morbidity and/or mortality. OBJECTIVES: To assess the effects on
      pregnancy outcome, and obstetric practice, of routine utero-placental Doppler
      ultrasound in first and second trimester of pregnancy in pregnant women at high
      and low risk of hypertensive complications. SEARCH STRATEGY: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (June 2010) and the
      reference lists of identified studies. SELECTION CRITERIA: Randomised and quasi
      randomised controlled trials of Doppler ultrasound for the investigation of utero
      placental vessel waveforms in first and second trimester compared with no Doppler
      ultrasound. We have excluded studies where uterine vessels have been assessed
      together with fetal and umbilical vessels. DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed the studies for inclusion, assessed risk of bias
      and carried out data extraction. We checked data entry. MAIN RESULTS: We found
      two studies involving 4993 participants. The methodological quality of the trials
      was good. Both studies included women at low risk for hypertensive disorders,
      with Doppler ultrasound of the uterine arteries performed in the second trimester
      of pregnancy. In both studies, pathological finding of uterine arteries was
      followed by low-dose aspirin administration.We identified no difference in short
      term maternal and fetal clinical outcomes.We identified no randomised studies
      assessing the utero-placental vessels in the first trimester or in women at high
      risk for hypertensive disorders. AUTHORS' CONCLUSIONS: Present evidence failed to
      show any benefit to either the baby or the mother when utero-placental Doppler
      ultrasound was used in the second trimester of pregnancy in women at low risk for
      hypertensive disorders. Nevertheless, this evidence cannot be considered
      conclusive with only two studies included. There were no randomised studies in
      the first trimester, or in women at high risk. More research is needed to
      investigate whether the use of utero-placental Doppler ultrasound may improve
      pregnancy outcome.

PMID- 20824876
TI  - Pharmacological treatment for depression during opioid agonist treatment for
      opioid dependence.
AB  - BACKGROUND: Lifetime prevalence of depression in subjects with opioid dependence
      is higher than in the general population (44-54% versus 16%) and represents a
      risk factor for morbidity and mortality. For patients on opioid agonist
      treatment, current prevalence rates of depression ranges between 10 and 30%,
      influencing negatively the outcome of the treatment. OBJECTIVES: To evaluate the
      efficacy and the acceptability of antidepressants for the treatment of depressed
      opioid dependents treated with opioid agonists. SEARCH STRATEGY: We searched
      Pubmed, EMBASE, CINAHL (to October 2009), CENTRAL (The Cochrane Library Cochrane
      Drug and Alcohol Group Specialised Register, issue 4, 2009), main electronic
      sources of ongoing trials, specific trial databases and reference lists of all
      relevant papers. SELECTION CRITERIA: Randomised and controlled clinical trials
      examining the efficacy of any antidepressant medication to treat depressed opioid
      dependents in treatment with opioid agonists. DATA COLLECTION AND ANALYSIS: Two
      authors independently screened and extracted data from studies. MAIN RESULTS:
      Seven studies, 482 participants, met the inclusion criteria.- Comparing
      antidepressant with placebo, no statistically significant results for dropouts.
      Selecting studies with low risk of bias, 325 participants, results favour
      placebo, RR 1.40 (Cl 95% 1.00 to 1.96). For severity of depression, results from
      two studies, 183 participants, favour antidepressants utilising Clinical Global
      Impression Scale RR 1.92 (CI 95% 1.26 to 2.94), while another study, 95
      participants, utilising the Hamilton Depression Rating Scale, did not find a
      statistically significant difference RR 0.96 (CI 95% 0.54 to 1.71). For adverse
      events, result favour placebo, four studies, 311 participants, RR 2.90 (Cl 95%
      1.23 to 6.86). For drug use, three studies, 211 participants, it was not possible
      to pool data because outcomes' measures were not comparable. Looking at singular
      studies, no statistically significant difference was seen.- Comparing different
      classes of antidepressants, the results favour tricyclics for severity of
      depression, two studies, 183 participants, RR 1.92 (Cl 95% 1.26 to 2.94) and
      favour placebo for adverse events, two studies, 172 participants, RR 3.11 (Cl 95%
      1.06 to 9.12). AUTHORS' CONCLUSIONS: There is low evidence, at the present,
      supporting the clinical use of antidepressants for the treatment of depressed
      opioid addicts in treatment with opioid agonists. There is a need of larger
      randomised studies investigating relevant outcomes, safety issues and reporting
      data to allow comparison of results.

PMID- 20824877
TI  - Formoterol versus short-acting beta-agonists as relief medication for adults and
      children with asthma.
AB  - BACKGROUND: Formoterol is a long-acting beta(2)-agonist but because it has a fast
      onset of action it can also be used as a relief medication. OBJECTIVES: To asses
      the efficacy and safety of formoterol as reliever therapy in comparison to short
      acting beta(2)-agonists in adults and children with asthma. SEARCH STRATEGY: We
      searched the Cochrane Airways Group Specialised Register and websites of clinical
      trial registers (for unpublished trial data), and we checked the Food and Drug
      Administration (FDA) submissions in relation to formoterol. The date of the most
      recent search was February 2010. SELECTION CRITERIA: Randomised, parallel-arm
      trials of at least 12 weeks duration in patients of any age and severity of
      asthma. Studies randomised patients to any dose of as-needed formoterol versus
      short-acting beta(2)-agonist. Concomitant use of inhaled corticosteroids or other
      maintenance medication was allowed, as long as this was not part of the
      randomised treatment regimen. DATA COLLECTION AND ANALYSIS: Two authors
      independently selected trials for inclusion in the review. Outcome data were
      extracted by one author and checked by the second author. We sought unpublished
      data on primary outcomes. MAIN RESULTS: This review includes eight studies
      conducted in 22,604 participants (mostly adults). Six studies compared formoterol
      as-needed to terbutaline whilst two studies compared formoterol with salbutamol
      as-needed. Background maintenance therapy varied across the trials. Asthma
      exacerbations and serious adverse events showed a direction of treatment effect
      favouring formoterol, of which one outcome reached statistical significance
      (exacerbations requiring a course of oral corticosteroids). In patients on short
      acting beta(2)-agonists, 117 people out of 1000 had exacerbations requiring oral
      corticosteroids over 30 weeks, compared to 101 (95% CI 93 to 108) out of 1000 for
      patients on formoterol as-needed. In patients on maintenance inhaled
      corticosteroids there were also significantly fewer exacerbations requiring a
      course of oral corticosteroids on formoterol as-needed (Peto OR 0.75; 95% CI 0.62
      to 0.91). There was one death per 1000 people on formoterol or on short-acting
      beta(2)-agonists. AUTHORS' CONCLUSIONS: In adults, formoterol was similar to
      short-acting beta(2)-agonists when used as a reliever, and showed a reduction in
      the number of exacerbations requiring a course of oral corticosteroids.
      Clinicians should weigh the relatively modest benefits of formoterol as-needed
      against the benefits of single inhaler therapy and the potential danger of long
      term use of long-acting beta(2)-agonists in some patients. We did not find
      evidence to recommend changes to guidelines that suggest that long-acting beta(2)
      agonists should be given only to patients already taking inhaled
      corticosteroids.There was insufficient information reported from children in the
      included trials to come to any conclusion on the safety or efficacy of formoterol
      as relief medication for children with asthma.

PMID- 20824878
TI  - Respiratory function monitoring to reduce mortality and morbidity in newborn
      infants receiving resuscitation.
AB  - BACKGROUND: A respiratory function monitor is routinely used in neonatal
      intensive care units to continuously measure and display airway pressures, tidal
      volume and leak during ventilation. During positive pressure ventilation in the
      delivery room, clinical signs are used to monitor the effectiveness of
      ventilation. The additional use of a respiratory function monitor during positive
      pressure ventilation in the delivery room might help to improve the effectiveness
      of ventilation. OBJECTIVES: To determine whether the use of a respiratory
      function monitor in addition to clinical assessment compared to clinical
      assessment alone in newborn infants resuscitated with positive pressure
      ventilation reduces mortality and morbidity. SEARCH STRATEGY: We searched the
      Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library,
      Issue 3, 2010), MEDLINE (January 1996 to March 2010), EMBASE (January 1980 to
      March 2010) and CINAHL (January 1982 to March 2010). Clinical trials registers
      and the abstracts of the Society for Pediatric Research and the European Society
      for Pediatric Research were searched from 2004 to 2009. No language restrictions
      were applied. SELECTION CRITERIA: We planned to include randomised and quasi
      randomised controlled trials and cluster trials that compared the use of a
      respiratory function monitor in addition to clinical assessment, compared to
      clinical assessment alone, in newborn infants resuscitated with positive pressure
      ventilation. DATA COLLECTION AND ANALYSIS: Two review authors independently
      evaluated the search results against the selection criteria. Data extraction and
      risk of bias assessment were not performed because there were no studies that met
      our inclusion criteria. MAIN RESULTS: No studies were found meeting the criteria
      for inclusion in this review AUTHORS' CONCLUSIONS: There is insufficient evidence
      to determine the efficacy and safety of a respiratory function monitor in
      addition to clinical assessment during positive pressure ventilation at neonatal
      resuscitation. Randomised clinical trials comparing positive pressure ventilation
      with and without a respiratory function monitor in addition to clinical
      assessment at neonatal resuscitation are warranted.

PMID- 20824879
TI  - Interventions for the treatment of keratocystic odontogenic tumours (KCOT,
      odontogenic keratocysts (OKC)).
AB  - BACKGROUND: The keratocystic odontogenic tumours (KCOTs) account for between
      about 2% and 11% of all jaw cysts and can occur at any age. They are more common
      in males than females with a male:female ratio of approximately 2:1. Although
      they are benign, KCOTs are locally very aggressive and have a tendency to recur
      after treatment, reported recurrence rates range from 3% to 60%. The traditional
      method for the treatment of most KCOTs is surgical enucleation. However, due to
      the lining of the cyst being delicate and the fact that they frequently recur,
      this method alone is not sufficient. Adjunctive surgical treatment has been
      proposed in addition to the surgical enucleation, such as removal of the
      peripheral bone (ostectomy) or resection of the cyst with surrounding bone (en
      bloc) resection. Other adjunctive treatments proposed are: cryotherapy (freezing)
      with liquid nitrogen and the use of the fixative Carnoy's solution placed in the
      cyst cavity after enucleation; both of which attempt to address residual tissue
      to prevent recurrence. OBJECTIVES: To assess the available evidence comparing the
      effectiveness of surgical interventions and adjuncts for the treatment of KCOTs.
      SEARCH STRATEGY: Databases searched were: the Cochrane Oral Health Group's Trials
      Register (to 28th July 2010), CENTRAL (The Cochrane Library 2010, Issue 3),
      MEDLINE (from 1950 to 28th July 2010), and EMBASE (from 1980 to 28th July 2010).
      The reference lists of all trials identified were cross checked for additional
      trials. There were no language restrictions and several articles were translated.
      SELECTION CRITERIA: Randomised controlled trials comparing one modality of
      surgical intervention with another with or without adjunctive treatment for the
      treatment of KCOTs. Adults, over the age of 18 with a validated diagnosis of
      solitary KCOTs arising in the jaw bones of the maxilla or mandible. Patients with
      known Gorlin syndrome were to be excluded. DATA COLLECTION AND ANALYSIS: Review
      authors screened trials for inclusion. Full papers were obtained for relevant and
      potentially relevant trials. If data had been extracted, it would have been
      synthesised using the fixed-effect model, if substantial clinical diversity were
      identified between studies we planned to use the random-effects model with
      studies grouped by action provided there were four or more studies included in
      the meta-analysis, and we would have explored the heterogeneity between the
      included studies. MAIN RESULTS: No randomised controlled trials that met the
      inclusion criteria were identified. AUTHORS' CONCLUSIONS: There are no published
      randomised controlled trials relevant to this review question, therefore no
      conclusions could be reached about the effectiveness or otherwise of the
      interventions considered in this review. There is a need for well designed and
      conducted randomised controlled trials to evaluate treatments for KCOTs.

PMID- 20824880
TI  - Different intensities of glycaemic control for pregnant women with pre-existing
      diabetes.
AB  - BACKGROUND: The optimal glycaemic control target in pregnant women with pre
      existing diabetes is unclear, although there is a clear link between high glucose
      concentrations and adverse birth outcomes. OBJECTIVES: To assess the effects of
      different intensities of glycaemic control in pregnant women with pre-existing
      type 1 or type 2 diabetes. SEARCH STRATEGY: We searched the Cochrane Pregnancy
      and Childbirth Group's Trials Register (7 May 2010). SELECTION CRITERIA: We
      included randomised controlled trials comparing different glycaemic control
      targets in pregnant women with pre-existing diabetes. DATA COLLECTION AND
      ANALYSIS: Two review authors assessed trial eligibility and risk of bias, and
      extracted data. MAIN RESULTS: We included three trials all in women with type 1
      diabetes (223 women and babies), and all with a high risk of bias. Two trials
      compared very tight (3.33 to 5.0 mmol/L fasting blood glucose (FBG)) with tight
      moderate (4.45 to 6.38) glycaemic control targets, with one trial of 22 babies
      reporting no perinatal deaths or serious perinatal morbidity. In the same trial,
      there were two birth defects in the very tight and none in the tight-moderate
      group with no significant differences in caesarean section between groups (risk
      ratio 0.92, 95% confidence interval (CI) 0.49 to 1.73). In these two trials
      glycaemic control was not significantly different between the very tight and
      tight-moderate groups by the third trimester, although one trial of 22 women
      found significantly less maternal hypoglycaemia in the tight-moderate group.In a
      trial of 60 women and babies comparing tight (</= 5.6 mmol/L FBG); moderate (5.6
      to 6.7); and loose (6.7 to 8.9) glycaemic control targets, there were two
      neonatal deaths in the loose and none in the tight or moderate groups. There were
      significantly fewer women with pre-eclampsia, fewer caesareans and fewer
      birthweights greater than 90th centile in the combined tight-moderate compared
      with the loose group. AUTHORS' CONCLUSIONS: In a very limited body of evidence,
      few differences in outcomes were seen between very tight and tight-moderate
      glycaemic control targets in pregnant women with pre-existing type 1 diabetes,
      including actual glycaemic control achieved. There is evidence of harm (increased
      pre-eclampsia, caesareans and birthweights greater than 90th centile) for 'loose'
      control (FBG above 7 mmol/L). Future trials comparing interventions, rather than
      glycaemic control targets, may be more feasible particularly for pregnant women
      with type 2 diabetes.

PMID- 20824881
TI  - Interventions for treating peripartum cardiomyopathy to improve outcomes for
      women and babies.
AB  - BACKGROUND: Peripartum cardiomyopathy (PPCM or PCMO) is a rare disease of unknown
      etiology, characterised by an acute onset of heart failure in women in the late
      stage of pregnancy or in the early months postpartum. OBJECTIVES: To assess the
      effectiveness and safety of any intervention for the care of women and/or their
      babies with a diagnosis of peripartum cardiomyopathy. SEARCH STRATEGY: We
      searched the Cochrane Pregnancy and Childbirth Group's Trials Register (27 July
      2010) and the reference lists of identified studies. SELECTION CRITERIA:
      Randomised and quasi-randomised controlled trials of any intervention for
      treating peripartum cardiomyopathy. Such interventions include: drugs; cardiac
      monitoring and treatment; haemodynamic monitoring and treatments; supportive
      therapies and heart transplant. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed the studies for inclusion, assessed risk of bias and
      carried out data extraction. Data entry was checked. MAIN RESULTS: We identified
      and included one pilot study, involving 20 women, undertaken in South Africa.
      Women were diagnosed postnatally and included in the study within 24 hours of
      diagnosis. AUTHORS' CONCLUSIONS: There are insufficient data to draw any firm
      conclusions. Treatment with bromocriptine appears promising, although women would
      be unable to breastfeed due to suppression of lactation.

PMID- 20824882
TI  - Interventions for preventing and treating hyperthyroidism in pregnancy.
AB  - BACKGROUND: Women with hyperthyroidism in pregnancy have increased risks of
      miscarriage, stillbirth, preterm birth, and intrauterine growth restriction; and
      they can develop severe pre-eclampsia or placental abruption. OBJECTIVES: To
      assess the effects of interventions for preventing or treating hyperthyroidism in
      pregnant women. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (28 July 2010). SELECTION CRITERIA: We
      intended to include randomised controlled trials comparing antithyroid treatments
      in pregnant women with hyperthyroidism. DATA COLLECTION AND ANALYSIS: Two review
      authors would have assessed trial eligibility and risk of bias, and extracted
      data. MAIN RESULTS: No trials were located. AUTHORS' CONCLUSIONS: As we did not
      identify any eligible trials, we are unable to comment on implications for
      practice, although early identification of hyperthyroidism before pregnancy may
      allow a woman to choose radioactive iodine therapy or surgery before planning to
      have a child. Designing and conducting a trial of antithyroid drugs for pregnant
      women with hyperthyroidism presents formidable challenges. Not only is
      hyperthyroidism a relatively rare condition, both of the two main drugs used have
      potential for harm, one for the mother and the other for the child. More
      observational research is required about the potential harms of methimazole in
      early pregnancy and about the potential liver damage from propylthiouracil.

PMID- 20824883
TI  - Tonsillectomy for periodic fever, aphthous stomatitis, pharyngitis and cervical
      adenitis syndrome (PFAPA).
AB  - BACKGROUND: PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis and
      cervical adenitis syndrome) is a rare clinical syndrome of unknown cause usually
      identified in children. OBJECTIVES: To assess the efficacy of tonsillectomy (with
      or without adenoidectomy) in children with PFAPA. SEARCH STRATEGY: We searched
      the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library, 2010 Issue 1); MEDLINE (PubMed); EMBASE; CINAHL; mRCT (metaRegister of
      clinical trials, including ClinicalTrials.gov); NRR (National Research Register);
      LILACS; KoreaMed; IndMed; PakMediNet; China Knowledge Network; CAB Abstracts; Web
      of Science; BIOSIS Previews; ICTRP (International Clinical Trials Registry
      Platform) and Google. The date of the last search was 21 January 2010. SELECTION
      CRITERIA: Randomised studies comparing adeno-/tonsillectomy with non-surgical
      treatment. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial
      quality and extracted data. MAIN RESULTS: Two trials involving 67 children were
      included. One high quality study demonstrated a dramatic benefit of
      adenotonsillectomy in children with PFAPA diagnosed according to rigid, standard
      criteria with a relative 'risk' (RR) of symptom resolution after 18 months of
      12.63 (95% CI 1.81 to 87.98) and a lower rate of episodes per patient-month (rate
      ratio 0.07; 95% CI 0.04 to 0.13). A less methodologically rigorous study enrolled
      some children with PFAPA, but probably included others with alternative types of
      recurrent pharyngitis, and performed tonsillectomy alone. This also demonstrated
      a significant benefit for surgery at six months: RR 1.93 (95% CI 1.11 to 3.36);
      rate ratio episodes per patient-month 0.10 (95% CI 0.04 to 0.28). The pooled
      relative risk of symptom resolution was 3.25 (95% CI 1.78 to 5.92) and the
      resulting number needed to treat (NNT) 2 (95% CI 1 to 3). AUTHORS' CONCLUSIONS:
      The trials included in this review reported follow up at 18 and six months
      respectively but it is well-established that children with PFAPA recover
      spontaneously and treatment can be administered to try and reduce the severity of
      individual episodes. Therefore, the parents and carers of children with PFAPA
      must weigh the risks and consequences of surgery (hospitalisation, a predictable
      period of time postoperatively away from school/nursery, the risks of surgery)
      against the alternative of a finite period of recurrent episodes of disease at
      predictable intervals, potentially requiring time off school and the regular use
      of medication. It is uncertain whether adenoidectomy combined with tonsillectomy
      adds any additional benefit to tonsillectomy alone.

PMID- 20824884
TI  - Ethical considerations in industry-sponsored multiregional clinical trials.
AB  - During the last several decades, the scientific and ethics communities have
      addressed important ethical issues in medical research, resulting in the
      elaboration and adoption of concepts, guidelines, and codes. Ethical issues in
      the conduct of Multiregional Clinical Trials have attracted significant attention
      mainly in the last two decades. With the globalization of clinical research and
      the rapid expansion to countries with a limited tradition of biomedical research,
      sponsors must proactively address local ethical issues, the adequacy of oversight
      as well as the applicability and validity of data, and scientific conclusions
      drawn from diverse patient populations. This paper highlights some core ethical
      principles and milestones in medical research, and, from an industry perspective,
      it discusses ethical issues that the clinical trial team may face when conducting
      Multiregional Clinical Trials (MRCT, clinical trials conducted at sites located
      across multiple geographic regions of the world). This paper further highlights
      the areas of consensus and controversies and proposes points to consider.

PMID- 20824885
TI  - Differences in hydrolytic abilities of two crude lipases from Geotrichum candidum
      4013.
AB  - The fungus Geotrichum candidum 4013 produces two types of lipases (extracellular
      and cell-bound). Both enzymes were tested for their hydrolytic ability to p
      nitrophenyl esters and compounds having a structure similar to the original
      substrate (triacylglycerols). Higher lipolytic activity of extracellular lipase
      was observed when triacylglycerols of medium- (C12) and long- (C18) chain fatty
      acids were used as substrates. Cell-bound lipase preferentially hydrolysed
      trimyristate (C14). The differences in the abilities of these two enzymes to
      hydrolyse p-nitrophenyl esters were observed as well. The order of extracellular
      lipase hydrolysis relation velocity was as follows: p-nitrophenyl decanoate > p
      nitrophenyl caprylate > p-nitrophenyl laurate > p-nitrophenyl palmitate > p
      nitrophenyl stearate. The cell-bound lipase indicates preference for p
      nitrophenyl palmitate. The most striking differences in the ratios between the
      activity of both lipases (extracellular : cell-bound) towards different fatty
      acid methyl esters were 2.2 towards methyl hexanoate and 0.46 towards methyl
      stearate (C18). The Michaelis constant (K(m) ) and maximum reaction rate (V(max)
      ) for p-nitrophenyl palmitate hydrolysis of cell-bound lipase were significantly
      higher (K(m) 2.462 mM and V(max) 0.210 U/g/min) than those of extracellular
      lipase (K(m) 0.406 mM and V(max) 0.006 U/g/min).

PMID- 20824886
TI  - Erratum: Probabilistic application of a fugacity model to predict triclosan fate
      during wastewater treatment.
AB  - The fate and partitioning of the antimicrobial compound, triclosan, in wastewater
      treatment plants (WWTPs) is evaluated using a probabilistic fugacity model to
      predict the range of triclosan concentrations in effluent and secondary
      biosolids. The WWTP model predicts 84% to 92% triclosan removal, which is within
      the range of measured removal efficiencies (typically 70% to 98%). Triclosan is
      predominantly removed by sorption and subsequent settling of organic particulates
      during primary treatment and by aerobic biodegradation during secondary
      treatment. Median modeled removal efficiency due to sorption is 40% for all
      treatment phases and 31% in the primary treatment phase. Median modeled removal
      efficiency due to biodegradation is 48% for all treatment phases and 44% in the
      secondary treatment phase. Important factors contributing to variation in
      predicted triclosan concentrations in effluent and biosolids include influent
      concentrations, solids concentrations in settling tanks, and factors related to
      solids retention time. Measured triclosan concentrations in biosolids and non
      United States (US) effluent are consistent with model predictions. However,
      median concentrations in US effluent are over-predicted with this model,
      suggesting that differences in some aspect of treatment practices not
      incorporated in the model (e.g., disinfection methods) may affect triclosan
      removal from effluent. Model applications include predicting changes in
      environmental loadings associated with new triclosan applications and supporting
      risk analyses for biosolids-amended land and effluent receiving waters.

PMID- 20824888
TI  - Isolation and characterization of the carbon catabolite-derepressing protein
      kinase Snf1 from the stress tolerant yeast Torulaspora delbrueckii.
AB  - We cloned a genomic DNA fragment of the yeast Torulaspora delbrueckii by
      complementation of a Saccharomyces cerevisiae snf1Delta mutant strain. DNA
      sequence analysis revealed that the fragment contained a complete open reading
      frame (ORF), which shares a high similarity with the S. cerevisiae energy sensor
      protein kinase Snf1. The cloned TdSNF1 gene was able to restore growth of the S.
      cerevisiae snf1Delta mutant strain on media containing nonfermentable carbon
      sources. Furthermore, cells of the Tdsnf1Delta mutant were unable to proliferate
      under nonfermenting conditions. Finally, protein domain analysis showed that
      TdSnf1p contains a typical catalytic protein kinase domain (positions 41-293),
      which is also present in other Snf1p homologues. Within this region we identified
      a protein kinase ATP-binding region (positions 48-71) and a consensus Ser/Thr
      protein kinase active site (positions 160-172).

PMID- 20824889
TI  - Susceptibility and resistance to ethanol in Saccharomyces strains isolated from
      wild and fermentative environments.
AB  - In this work, we apply statistical modelling techniques to study the influence of
      increasing concentrations of ethanol on the overall growth of 29 yeast strains
      belonging to different Saccharomyces and non-Saccharomyces species. A modified
      Gompertz equation for decay was used to objectively estimate the noninhibitory
      concentration (NIC) and minimum inhibitory concentration (MIC) for the assayed
      strains to ethanol, which are related to the susceptibility and resistance of
      yeasts to this compound, respectively. A first ANOVA analysis, grouping strains
      as a function of their respective Saccharomyces species, revealed that S.
      cerevisiae was the yeast with the highest, and statistically significant, ethanol
      resistance value. Then, a second factorial ANOVA analysis, using the origin of
      strains (wild or fermentative) and their taxonomic classification (S. cerevisiae,
      S. paradoxus or S. bayanus var. uvarum) as categorical predictor variables,
      showed that no significant differences for the NIC and MIC parameters were found
      between both ecological niches within the same species, indicative that these
      physiological characteristics were presumably not modified throughout the
      adaptation to human-manipulated fermentative environments. Finally, differences
      among selected strains with respect to ethanol tolerance were correlated to the
      initial contents of unsaturated fatty acids, mainly oleic acid.

PMID- 20824890
TI  - Measuring oxidative DNA damage and DNA repair using the yeast comet assay.
AB  - Chromosomal DNA damage can be a result of several processes and agents of
      endogenous or exogenous origin. These cause strand breaks or oxidized bases that
      lead to strand breaks, which relax the normally supercoiled genomic DNA and
      increase its electrophoretic mobility. The extent of DNA damage can be assessed
      by single cell gel electrophoresis, where the chromosomal DNA migration distance
      correlates with the extent of DNA damage. This technique has been used for a
      variety of applications with several organisms, but only a few studies have been
      reported for Saccharomyces cerevisiae. A possible reason for this absence is that
      low cellular DNA content could hamper visualization. Here we report an
      optimization of the comet assay protocol for yeast cells that is robust and
      sensitive enough to reproducibly detect background DNA damage and oxidative
      damage caused by hydrogen peroxide. DNA repair was observed and quantified as
      diminishing comet tail length with time after oxidative stress removal in a
      process well described by first-order kinetics with a tail length half-life of 11
      min at 37  degrees C. This is, to our knowledge, the first quantitative
      measurement of DNA repair kinetics in S. cerevisiae by this method. We also show
      that diet antioxidants protect from DNA damage, as shown by a three-fold decrease
      in comet tail length. The possibility of assessment of DNA damage and repair in
      individual cells applied to the model organism S. cerevisiae creates new
      perspectives for studying genotoxicity and DNA repair.

PMID- 20824891
TI  - Hemangioma in the newborn: increased incidence after chorionic villus sampling.
AB  - OBJECTIVES: This study was designed to compare the effects of transcervical
      chorionic villus sampling (CVS) and amniocentesis on the prevalence of
      hemangiomas of infancy. METHODS: This is a cohort study of 250 consecutive
      assessable transabdominal amniocentesis procedures and 250 consecutive assessable
      transcervical CVS procedures performed between January and September 2002.
      Parents were asked to fill out a questionnaire regarding the presence of any type
      of skin lesions. Based on the responses to the questionnaire, children were
      invited to undergo a physical examination to confirm hemangiomas. RESULTS:
      Questionnaires were returned in 78% of the CVS group (195/250) and in 72% of the
      amniocentesis group (180/250). Based on the responses in the questionnaire, 78
      children in the CVS group and 42 in the amniocentesis group underwent a physical
      examination. One or more hemangiomas were present in 53 of 195 (27.2%) children
      in the CVS group versus 17 of 180 (9.4%) children in the amniocentesis group
      (odds ratio 3.6, 95% CI: 2.0-6.5). There was no difference in congenital
      abnormalities between the two groups. CONCLUSION: Transcervical CVS is associated
      with a significantly increased prevalence of hemangiomas compared with
      amniocentesis. The clinical features of these hemangiomas do not differ from
      natural hemangiomas and complications of these hemangiomas are very rare.

PMID- 20824892
TI  - Diagnostic yield by supplementing prenatal metaphase karyotyping with MLPA for
      microdeletion syndromes and subtelomere imbalances.
AB  - OBJECTIVE: The aim of the study was to retrospectively assess the relevance of
      using multiplex ligation-dependent probe amplification (MLPA) for detection of
      selected microdeletion syndromes (22q11, Prader-Willi/Angelman, Miller-Dieker,
      Smith-Magenis, 1p-, Williams), the reciprocal microduplication syndromes and
      imbalance at the subtelomere regions of chromosomes in a routine prenatal
      setting. METHOD: A total of 530 prenatal samples were analysed by commercial MLPA
      kits (SALSA P064, P036 and P069) in addition to rapid aneuploidy testing and G
      band karyotyping. RESULTS: Among the prenatal samples with a normal metaphase
      karyotype, nine submicroscopic imbalances were detected: seven 22q11 deletions
      (Velocardiofacial/DiGeorge syndrome), one 15q11 deletion (Prader-Willi syndrome)
      and one terminal deletion of the short arm of chromosome 4 (Wolf-Hirschhorn
      syndrome). All imbalances were found in amniocentesis (AC) taken due to fetal
      structural malformation and/or other ultrasound scan (US) detected abnormality.
      The diagnostic yield was 4.1% in the subgroup with structural malformation and
      1.6% in the subgroup with other US abnormality. CONCLUSION: The data set
      substantiates that additional MLPA analyses for selected microdeletions and
      subtelomere imbalances are valuable in routine prenatal diagnostics, when a
      malformation(s) and/or other abnormalities are detected by US. In contrast, the
      additional MLPA analyses gave no diagnostic yield in case of increased nuchal
      translucency (NT).

PMID- 20824893
TI  - Assessment of regional right ventricular longitudinal functions in fetus using
      velocity vector imaging technology.
AB  - OBJECTIVES: The velocity vector imaging (VVI) technique is useful to assess
      regional myocardial mechanics. The aim of this study was to evaluate the
      usefulness of this technology in assessing regional right ventricular
      longitudinal functions in the fetus and to establish a nomogram of the right
      ventricle (RV). METHODS: We studied 170 healthy fetuses that were divided into
      five groups based on gestational age. Dynamic digital images of four chambers
      were collected and analyzed off-line. The longitudinal VVI parameters were
      calculated in the right free wall and ventricular septum, respectively. RESULTS:
      A total of 151 out of 170 fetuses (89%) were successfully analyzed using VVI,
      with good inter- and intra-observer agreements. Normal values for velocity,
      strain, and strain rate were established. The tissue velocity gradually decreased
      from basal to apical segment (P < 0.05), whereas strain and strain rate remained
      stable. The tissue velocity increased with gestational age (P < 0.05), whereas
      strain and strain rate were stable (P > 0.05). CONCLUSION: Fetal myocardial
      velocity, strain, and strain rate measurements are easy to obtain and are
      reproducible. From mid-to-late gestation, the longitudinal tissue velocity of the
      RV increases with gestational age, whereas strain and strain rate remain stable.
      These results indicate that myocardial contractility is established in mid
      gestation and remains constant throughout gestation.

PMID- 20824894
TI  - A prospective double-blind randomized placebo-controlled study of the effect of
      saffron (Crocus sativus Linn.) on semen parameters and seminal plasma antioxidant
      capacity in infertile men with idiopathic oligoasthenoteratozoospermia.
AB  - Male factor infertility is a multifactorial disorder that affects a significant
      percentage of infertile couples; however, many of them remained untreated. In
      recent years, considerable numbers of infertile men have sought 'herbal remedies'
      as an effective treatment. Among 'herbal remedies', saffron is recommended for
      male infertility in our community. The effect of saffron was evaluated compared
      with placebo for the treatment of idiopathic male factor infertility. The study
      included 260 infertile men with idiopathic oligoasthenoteratozoospermia (OAT) who
      were randomized to saffron 60 mg/day (130, group 1) or a similar regimen of
      placebo (130, group 2) for 26 weeks. The two groups were compared for changes in
      semen parameters and total seminal plasma antioxidant capacity. Saffron
      administration did not result in beneficial effects. At the end of the study no
      statistically significant improvements were observed in either group in any of
      the studied semen parameters (sperm density, morphology and motility) (all p =
      0.1). At the end of the trial, patients in group 1 had a mean motility of 25.7 +/
      2.4%, which was not statistically different from the mean of 24.9 +/- 2.8% in
      the placebo group (p = 0.1). Normal sperm morphology was 18.7 +/- 4.7% and 18.4
      +/- 4.3%, in groups 1 and 2, respectively (p = 0.1). Patients treated with
      saffron and placebo had a mean sperm density of 20.5 +/- 4.6% and 21.4 +/- 4.6%
      per mL, respectively (p = 0.1). Saffron administration did not improve total
      seminal plasma antioxidant capacity, compared with baseline (p = 0.1) and placebo
      subjects (p = 0.1). Based on Pearson correlations, each semen parameter did not
      correlate significantly with treatment duration, including sperm density (r =
      0.146, p = 0.13), percent of motile sperm (r = 0.145, p = 0.15) and percent of
      sperm with normal morphology (r = 0.125, p = 0.30). Saffron does not
      statistically significantly improve semen parameters in infertile men with
      idiopathic OAT. If medical professionals want to prescribe herbal remedies for
      male infertility, previous rigorous scientific investigations, documenting their
      safety and efficacy are required.

PMID- 20824895
TI  - Rift Valley Fever: scientific pathways to public health prevention and response.
      Proceedings of a workshop. May 2008. Nairobi.

PMID- 20824897
TI  - [Proceedings of the 41st seminar for clinical laboratory technician held by the
      Japanese Society of Clinical Pathology. June 4-8, 2007, Tokyo, Japan].

PMID- 20824896
TI  - Molecular origins of lung cancer - prospects for personalized prevention and
      therapy. Proceedings and abstracts of a meeting. January 10-14, 2010. San Diego,
      California, USA.

PMID- 20824898
TI  - Human papillomavirus-a powerful predictor of survival in patients with
      oropharyngeal cancer.

PMID- 20824899
TI  - Hepatectomy-induced metastasis.

PMID- 20824900
TI  - oral bisphosphonate use may protect women from breast cancer.

PMID- 20824901
TI  - T cells as trained killers.

PMID- 20824902
TI  - Breast cancer cells-escape artists.

PMID- 20824903
TI  - Digital infrared breast scan shows promise for detecting cancer.

PMID- 20824904
TI  - Patients with high-risk aPl benefit from risk-adapted consolidation therapy.

PMID- 20824905
TI  - Laparoscopic rectal cancer surgery is safe and effective.

PMID- 20824906
TI  - Lenalidomide for bortezomib-resistant multiple myeloma.

PMID- 20824907
TI  - Lenalidomide efficacy in bortezomib-resistant myeloma.

PMID- 20824909
TI  - Commentary: one snip doesn't fit all.

PMID- 20824908
TI  - Cost effectiveness of venous thromboembolism pharmacological prophylaxis in total
      hip and knee replacement: a systematic review.

PMID- 20824910
TI  - [Combined local and vaginal therapy in Buruli ulcer].

PMID- 20824911
TI  - Rebuilding after Katrina. Storm changed costs, dynamics of providing care.

PMID- 20824912
TI  - Taking a plunge. AHA's income sees big drop in 2009.

PMID- 20824914
TI  - Moving toward reform. Medco acquiring United BioSource.

PMID- 20824913
TI  - Survey: changes ahead. Employees to pick up more of the cost.

PMID- 20824915
TI  - Fla. does stay with AMA. State group had joined others to protest reform.

PMID- 20824916
TI  - This change is good. Next year the list will recognize healthcare's 'most
      influential'.

PMID- 20824917
TI  - Grappling with a leviathan. Right to contract provides needed counterbalance to
      government power in healthcare.

PMID- 20824918
TI  - Searching for answers. Suicide experts point to risk factors, but say problem
      'knows no boundary'.

PMID- 20824919
TI  - Largest medical schools. Ranked by total active enrollment for the 2009-10 school
      year.

PMID- 20824920
TI  - Another Medicaid boost...but states shouldn't plan on getting any more.

PMID- 20824921
TI  - Negative forecast. Medicare drop exacerbates not-for-profit outlook.

PMID- 20824922
TI  - Seeking Catholic cohesion. CHA report stresses cooperation over consolidation.

PMID- 20824923
TI  - Recipe for necessity. Providers wary of delays from new RAC reviews.

PMID- 20824924
TI  - Post-pandemic. Experts say H1N1 preparedness paid off.

PMID- 20824925
TI  - Docs contemplate meaning. Industry pushes meaningful use through incentives.

PMID- 20824926
TI  - Reform the reform studies. Everyone with a calculator has a reform law cost
      projection.

PMID- 20824927
TI  - Falling flat. Survey shows base salaries remain stagnant for a second year, but
      incentives help boost overall pay for some execs; others see cuts.

PMID- 20824928
TI  - There is no time to waste as GPs grasp the scale of the challenge.

PMID- 20824929
TI  - Uncertainty still dogs PCTs.

PMID- 20824931
TI  - On fatal distractions.

PMID- 20824930
TI  - Quality accounts. Trusts dodge scrutiny by omitting vital measures.

PMID- 20824932
TI  - The new healthcare revolution.

PMID- 20824933
TI  - Collaboration. No trust is an island.

PMID- 20824934
TI  - Public health. How Liverpool scored a home run on housing.

PMID- 20824935
TI  - Innovation. Property is wealth.

PMID- 20824936
TI  - ["Don't drink your waste" (1)].

PMID- 20824937
TI  - [Proceedings of the 42nd seminar for clinical laboratory technician held by
      Japanese Society of Clinical Pathology. June 9-13, 2008, Tokyo, Japan].

PMID- 20824938
TI  - Retraction notice to "Effects of organic ligands on fractionation of rare earth
      elements (REEs) in hydroponic plants: an application to the determination of
      binding capacities by humic acid for modeling" [Chemosphere 65 (11) (2006) 1942
      1948].

PMID- 20824939
TI  - Challenges and dilemmas: fieldwork with upland minorities in socialist Vietnam,
      Laos and southwest China.
AB  - The Chinese, Vietnamese and Lao spaces within the upland Southeast Asian massif,
      sheltering over 80 million people belonging to geographically dispersed and
      politically fragmented minority populations, have only recently reopened to
      overseas academic endeavours. Undertaking social sciences research there among
      ethnic minority groups is underscored by a specific set of challenges, dilemmas,
      and negotiations. This special issue brings together Western academics and post
      fieldwork doctoral students from the realms of social anthropology and human
      geography, who have conducted in-depth fieldwork among ethnic minorities in
      upland southwest China, northern Vietnam, and southern Laos. The articles provide
      insights into the struggles and constraints they faced in the field, set against
      an understanding of the historical context of field research in these locales. In
      this unique context that nowadays interweaves economic liberalisation with
      centralised and authoritarian political structures, the authors explore how they
      have negotiated and manoeuvred access to ethnic minority voices in complex
      cultural configurations. The ethical challenges raised and methodological
      reflections offered will be insightful for others conducting fieldwork in the
      socialist margins of the Southeast Asian massif and beyond. This specific context
      is introduced here, followed by a critique of the literature on the core themes
      that contributors raise.

PMID- 20824940
TI  - A heuristic blunder: notes on an ethnographic situation in southwest China.
AB  - During long-term fieldwork the increasing involvement of the ethnographer in the
      lives of others raises a series of methodological and ethical issues. These can
      become even more pronounced when one is working with ethnic minorities in a
      socialist country. Yet, a seldom acknowledged reality of ethnographic fieldwork
      experience are the 'little failures' that occur along the way, alongside
      ethnographic blunders. I argue that these are difficult to avoid and can be part
      of an important learning process, oftentimes for both researcher and researched.
      Through the detailed description of a blunder that the author made during his
      research in southwest China with members of the Drung ethnic minority, this
      article advocates for the heuristic value of such mishaps, suggesting that one
      can learn a lot from accidents and unexpected events while undertaking in-depth
      ethnographic fieldwork. In this case, this helped to shed light on the
      micropolitics of Drung village life in southwest Yunnan, and the place of a
      'minority nationality' in wider Chinese society.

PMID- 20824941
TI  - Navigating fieldwork politics, practicalities and ethics in the upland
      borderlands of northern Vietnam.
AB  - In this article, I detail and evaluate the negotiations I had to broker to
      conduct ethnographic research on marketplace vendors and trade in the upland
      borderlands of northern Vietnam. Working with the analogy of the numerous 'lines'
      I was constrained by, had to manoeuvre around, and at times crossed over, I begin
      with a discussion of the 'official lines' or state regulations imposed upon my
      research and how I worked with, or negotiated these limitations. I then reveal
      the important 'border guards' or gatekeepers, such as local state actors and also
      field assistants, who enabled or constrained access to informants in numerous
      different ways. I also highlight the logistical and practical lines that I had to
      accept and indeed, often draw, to accomplish my study. I conclude with a
      consideration of how friendships in the field drew me beyond the lines I had
      originally drawn around my research. These relationships furthered my anxiety
      over the possibilities for conducting research that ultimately contributes
      towards social justice in a constrained political setting such as that which
      presently characterises Vietnam.

PMID- 20824942
TI  - [Increasing occurrence of congenital syphilis].

PMID- 20824943
TI  - "Our hearts and spirits were broken": the medical world from the perspective of
      German-Jewish patients in the seventeenth and eighteenth centuries.

PMID- 20824944
TI  - Turning the tables: Freud's response to antisemitism in "The Interpretation of
      Dreams".

PMID- 20824945
TI  - [Molecular imaging].

PMID- 20824947
TI  - Cardiovascular devices; reclassification of certain percutaneous transluminal
      coronary angioplasty (PTCA) catheters. Final rule.
AB  - The Food and Drug Administration (FDA) is reclassifying the device type, standard
      percutaneous transluminal coronary angioplasty (PTCA) catheters, from class III
      (premarket approval) into class II (special controls). Cutting/scoring PTCA
      catheters remain in class III and continue to require premarket approval
      applications (PMAs). FDA is reclassifying these devices in accordance with the
      Federal Food, Drug, and Cosmetic Act (the act). Elsewhere in this issue of the
      Federal Register, FDA is announcing the availability of a guidance document
      entitled ''Guidance for Industry and FDA Staff: Class II Special Controls
      Guidance Document for Certain Percutaneous Transluminal Coronary Angioplasty
      (PTCA) Catheters'' that will serve as the special control for the reclassified
      device type.

PMID- 20824946
TI  - Public participation in post-Fordist urban green space governance: the case of
      community gardens in Berlin.
AB  - This article examines citizen participation in the governance of contemporary
      urban green space. Rather than exploring normative questions of ideal forms of
      participatory democracy, it focuses on changing roles and relationships between
      local state and non-state actors in order to identify and explain the changing
      nature of participation. I argue that neoliberal urban restructuring has changed
      the conditions for participation and thus participation itself in fundamental
      ways and that we need an account of changes in statehood and governance in order
      to capture this conceptually. Based on the case of community gardens in Berlin,
      the article discusses the extent to which this changed relationship is expressed
      by current citizen participation as well as the potential and problems that
      result from it. My empirical results show the emergence of a new political
      acceptance of autonomously organized projects and active citizen participation in
      urban green space governance. The central argument of this article is that this
      new acceptance can be conceptualized as an expression of the neoliberalization of
      cities. Nevertheless, this neoliberal strategy at the same time leads to complex
      and contradictory outcomes and the resulting benefits are also acknowledged.

PMID- 20824948
TI  - The Peruvian diaspora: portrait of a migratory process.
AB  - Since the 1980s and especially the 1990s, Peru has become a nation of emigrants.
      Emigration has become massive over the past two decades, and the Peruvian
      populations of the United States, Japan, and Spain have tripled in less than a
      decade. A survey of households in five localities, three urban and two rural, in
      and around Lima helps to reveal the special character of this emigration. It
      tends to involve older and better-educated individuals than are typical of
      international migration and to target a wider variety of destinations. Moreover,
      it is a multiclass phenomenon. The economic, political, and social crisis brought
      about by a change in the economic model, two decades of terrorism, and a
      succession of failed democratic administrations has affected the society as a
      whole, and international migration seems to operate as an escape valve.

PMID- 20824949
TI  - Leaving to get ahead: assessing the relationship between mobility and inequality
      in Peruvian migration.
AB  - Analysis of the impact of international migration on the socioeconomic conditions
      of migrants and their families in Peru, using data from the Latin American
      Migration Project, suggests that international migration contributes to
      individuals' socioeconomic well-being. While those who migrate tend to come from
      relatively privileged backgrounds in the first place, they gain further relative
      economic advantage by moving out of the country. A possible implication of this
      is that the growing international migration observed today is likely to
      exacerbate rather than ameliorate the already uneven distribution of income and
      rigid socioeconomic hierarchy in Peru.

PMID- 20824951
TI  - Outsourcing care: how Peruvian migrants meet transnational family obligations.
AB  - Migration from Peru has increased dramatically over the past decade, but the
      social and relational repercussions of these transnational movements have not yet
      been fully explored. Examination of the way migrants manage their
      responsibilities to dependent kin in Peru reveals that child fostering makes it
      possible for adults to migrate in search of better work opportunities by ensuring
      care for their children and company for their older relatives. For Peruvians
      engaging in labor migration, child fostering tempers some of the challenges of
      continuing to participate in established social networks from a distance.

PMID- 20824953
TI  - Le trauma.

PMID- 20824954
TI  - Sialidases in biological systems.
AB  - Sialidases are very common in biological systems. They are found particularly in
      diverse virus families and bacteria, but also in protozoa, some invertebrates and
      mammalian. The enzymes differ in their biochemical properties, e.g., kinetics,
      binding affinity or substrate preference. Nevertheless, they have conserved
      domains and structural similarities. Their functions offer a wide spread spectrum
      in nutrition, pathomechanisms and communication in mammalian. In pathogen
      organisms sialidases give insight in coevolution and interaction between pathogen
      or commensale and host. As well the enzymes are of interest in drug targeting,
      like neuraminidase inhibitors of influenza viruses.

PMID- 20824955
TI  - Effect of selected drugs on plasma asymmetric dimethylarginine (ADMA) levels.
AB  - Asymmetric dimethylarginine (ADMA) is an endogenous methylated amino acid derived
      from arginine which can inhibit the activity of nitric oxide synthases. In
      various pathological states such as hypercholesterolemia, hyperglycemia,
      hyperhomocysteinemia, hypertension, coronary artery disease, heart failure, and
      stroke, plasma levels of ADMA may be increased and lead to inhibition of NO
      synthesis and endothelial dysfunction. Inhibition of ADMA synthesis or
      intensification of metabolism of this compound might indirectly lower ADMA.
      Antioxidants, estrogen, vitamin A, angiotensin converting enzyme inhibitors,
      angiotensin AT1 receptor antagonists, and also some hypolipemic, hypoglycemic and
      beta-adrenoreceptor blocking drugs decrease ADMA levels. In some situations like
      neurological disorders, decreased plasma levels of ADMA are noticed and drugs
      increasing the concentration of this compound could exert protective effects. It
      is reasonable to explore which drugs can increase or decrease ADMA levels and
      what their mechanism of that action is.

PMID- 20824956
TI  - Synthesis and evaluation of chitosan-graft-polyethylenimine as a gene vector.
AB  - The objective of this study was to prepare a series of chitosan-graft
      polyethylenimine (chitosan-g-PEI) copolymers as gene carriers with high
      transfection efficiency and low cytotoxicity. Chitosan-g-PEIs with different
      molecular weights and segments were successfully synthesized by both oxidation
      and imine reactions and then characterized by 1H NMR, IR, UV and DSC. All types
      of Chitosan-g-PEIs prepared were found to interact efficiently with plasmid DNA
      (pIRES2-EGFP-p53) on DNA retardation assays. The Chitosan-g-PEI/DNA complex had a
      diameter of approximately 200 nm and a surface potential of zeta = +10.0 mV when
      the N/P ratio was 15/1. Optimal transfection efficiency of the chitosan-g-PEI/DNA
      complex was observed at N/P = 45/1 on HepG2 cells, with significantly lower
      toxicity compared with the gold standard PEI 25 kd. Moreover, the results showed
      that the toxicity increased with increasing molecular weight of the PEI segment
      in chitosan-g-PEI. Based on these results, chitosan-g-PEI with different chitosan
      and PEI segments of could be used for gene expression on different levels, and
      some of them may appear as potential candidates for gene delivery systems.

PMID- 20824957
TI  - Lipoic acid nanoparticles: effect of polymeric stabilizer on appetite
      suppression.
AB  - Alpha-lipoic acid (ALA), which is common in the human body, is efficacious in
      appetite suppression. However, its typical formulations of salt or micronized
      crystals cannot satisfy the desired bioavailability requirements for appetite
      suppression due to low absorption and a short plasma half-life. Herein, we
      describe a new ALA nanoparticulate formulation produced by nano-comminution using
      polymeric stabilizers, such as hydroxypropyl cellulose, Pluronic F127, and
      polyvinylpyrrolidone. Nanoparticles of similar sizes did not show any remarkable
      differences in the in vitro release profiles. However, the in vivo results from
      food intake studies in mice demonstrated that the hydroxypropyl cellulose case
      had the largest improved efficacy among the three polymeric stabilizer cases.
      Compared to the nanosuspension formulations, the powder formulations of
      nanoparticles had improved efficacy in reducing food intake for six hours,
      possibly because of the delayed release kinetics. Therefore, the ALA powder
      formulation of nanoparticles is a candidate to replace the current formulations
      to achieve proper appetite suppression.

PMID- 20824958
TI  - Preparation and characterization of solid lipid nanoparticles loaded with
      epirubicin for pulmonary delivery.
AB  - In this study, epirubicin (EPI)-loaded solid lipid nanoparticles (EPI-SLNs) were
      successfully prepared as an inhalable formulation for treatment of lung cancer.
      The physicochemical properties and in vitro pulmonary deposition of EPI-SLNs was
      studied. Pharmacokinetics were studied in rats by inhalation administration of
      EPI-SLNs and EPI-solutions respectively, the concentrations of EPI in blood and
      lungs were determined. Cytotoxicity was determined in A549 alveolar epithelial
      cells and found to be not toxic in blank SLNs and higher cytotoxicity of EPI-SLNs
      was found compared with that of EPI solution. In vitro deposition study suggested
      that SLNs remained stable during nebulization with improved respirable fraction
      (RF) compared to EPI-solutions. In vivo pharmacokinetic study showed that the
      drug concentration achieved by inhalation of EPI-SLNs was much higher than the
      drug concentration in plasma. Furthermore the drug concentration in lungs after
      inhalation of EPI-SLNs was much higher than that after administration of
      epirubicin solution. These findings suggest that EPI-SLNs could be used as an
      inhalable delivery system for treatment of lung cancer.

PMID- 20824959
TI  - Physicochemical characterization of the photosensitizers TPCS2a and TPPS2a 1.
      Spectroscopic evaluation of drug--solvent interactions.
AB  - The spectroscopic properties of the patented photosensitizer meso-tetraphenyl
      chlorin disulphonate (TPCS2a), intended for use in photochemical internalization
      (PCI) technology, and the chemically related photosensitizer meso-tetraphenyl
      porphyrin disulphonate (TPPS2a) were characterized in 14 organic solvents of
      varying polarity and amphiprotic properties. Absorption spectra and fluorescence
      emission spectra were acquired, and Stokes' shifts and fluorescence quantum
      yields determined. These investigations yield information on the physicochemical
      interactions between the photosensitizers and their surroundings (i.e., the
      physiological environment in vivo or the vehicle in vitro), which is essential
      for the further development of drug formulations. TPPS2a and TPCS2a are rigid
      molecules, built up by conjugated ring systems which possess limited interactions
      with the surroundings in the ground state (So). Accordingly, only small spectral
      shifts were observed in the absorption spectra, as well as in the fluorescence
      emission spectra. TPPS2a is spatially more planar than TPCS2a, which is twisted
      as a result of reduction of a double bond in the core. However, the two compounds
      were quite similarly influenced by properties of the solvents, indicating that
      twisting has limited importance in the interactions of the two photosensitizers
      with their environment. Both compounds possess a high character of pi-pi*
      transition upon light exposure, supported by high molar absorption coefficients.
      The fluorescence quantum yields (phi(f)) were influenced by solvent properties to
      a larger extent than the spectral shifts. This might indicate that the reactivity
      of the first excited singlet state (S1*) significantly depends on the properties
      of the surroundings.

PMID- 20824960
TI  - Cytotoxicity of amorphous silica particles against macrophage-like THP-1 cells
      depends on particle-size and surface properties.
AB  - Recent studies have indicated that amorphous silica particles (SPs) show
      cytotoxicity against various types of cells, including macrophages. However, the
      mechanism of cell death has not been determined, and systematic investigations of
      the relationship between particle characteristics and cytotoxicity are still
      quite limited. Here, we compared the cytotoxicity of SPs of various sizes (30
      1000 nm) and surface properties against differentiated THP-1 human macrophage
      like cells. We found that 300 and 1000 nm SPs showed cytotoxicity against THP-1
      cells, whereas 30, 50, and 70 nm SPs did not induce cell death. We demonstrated
      that 1000 nm SP showed strong cytotoxicity that depended on reactive oxygen
      species but was independent of caspases. Furthermore, we showed that surface
      modification of 1000 nm SPs dramatically suppressed their cytotoxicity. Our
      results suggest that systematic evaluation of the association between particle
      characteristics and biological effects is necessary for the creation of safe SPs.

PMID- 20824961
TI  - Photokilling of bacteria by curcumin in selected polyethylene glycol 400 (PEG
      400) preparations. Studies on curcumin and curcuminoids, XLI.
AB  - Curcumin, bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, is a yellow
      orange pigment which can be synthesised chemically or isolated from the plant
      Curcuma longa L. Curcumin has a rather broad absorption peak in the range 300-500
      nm (maximum approximately 430 nm) and has potential as a photosensitiser for
      treatment of localised superficial infections in e.g., the mouth or skin.
      Previously, we have demonstrated phototoxic effects of curcumin in selected
      aqueous preparations against both gram-positive Enterococcus faecalis and
      Streptococcus intermedius and gram-negative Escherichia coil bacteria in vitro.
      One of the most efficient preparations was curcumin in polyethylene glycol (PEG
      400) dissolved in phosphate buffered saline (PBS), pH 6.1. In this study the
      solubilising effect of PEG 400 on curcumin molecules and the in vitro phototoxic
      effects of these preparations were further evaluated. The effect of varying the
      curcumin concentration (2.50 microM -25.00 microM), the radiant exposure (0.5-30
      J/cm2) and the physical state of curcumin against the survival of E. coli was
      investigated. PEG 400 showed an increasing physically stabilising effect towards
      crystallisation of curcumin in aqueous preparation with increasing concentrations
      (2.5%-10.0% v/v). Despite a higher solubility of curcumin with increasing PEG 400
      concentrations, the surfactant reduced the phototoxicity of curcumin against E.
      coil. The highest phototoxic effect was obtained when curcumin was present in the
      least physically stable preparation, a stock solution in ethanol added to PBS
      with or without the lowest test concentration of PEG 400 (2.5% v/v). The obtained
      phototoxic effect can be increased by increasing the irradiation dose or by
      choosing an optimal curcumin concentration. E. faecalis was efficiently killed by
      the lowest concentration of curcumin in combination with the lowest radiant
      exposure when curcumin was dissolved in certain PEG solutions (< 0.02% survival),
      but showed no reduction when exposed to preirradiated curcumin.

PMID- 20824962
TI  - Synergistic effects of rMSCs and salidroside on the experimental hepatic
      fibrosis.
AB  - Rat mesenchymal stem cells (rMSCs) and salidroside have been applied in the
      treatment of hepatic fibrosis. The present study aimed to investigate the
      mechanism of hepatic differentiation of rMSCs in vitro and synergistic effects of
      rMSCs and salidroside on the experimental hepatic fibrosis in rats. rMSCs treated
      with 10 microg/mL, 20 microg/mL and 50 microg/mL salidroside were taken at 14
      days and the proteins were subjected to western blot analysis. Hepatic fibrosis
      was induced in rats by administration of porcine serum for 8 weeks. Then, rats
      were randomly divided into 6 groups: control group, hepatic fibrosis group
      (model), salidroside group, rMSCs group and rMSCs plus salidroside group. Four
      weeks later, the localization and differentiation of rMSCs were determined. To
      evaluate the improvement of liver injury, the pathology of hepatocytes (or liver)
      and serum transforming growth factor-beta1 (TGF-beta1) were assessed. Induced
      rMSCs expressed alpha-fetoprotein (AFP) and albumin (ALB), which suggested rMSCs
      differentiated towards hepatocytes; moreover, E-adherin and beta-catenin were
      involved in the hepatic differentiation of rMSCs. In experiments of rMSCs
      transplantation, the amount of collagen in the liver of rMSCs plus salidroside
      treated rats was significantly lowered accompanied by reduced expression of TGF
      beta1, when compared to the control group and rMSCs group. These findings
      suggested the synergistic effects of rMSCs transplantation and salidroside on
      hepatic fibrosis. Salidroside could differentiate rMSCs towards hepatocytes and E
      adherin and beta-catenin were involved in the hepatic differentiation of rMSCs.
      Treatment with rMSCs transplantation and salidroside exerted synergistic effects
      on the experimental hepatic fibrosis via suppressing the expression of TGF-beta1.

PMID- 20824963
TI  - Captopril-dependent inhibition of collagen biosynthesis in cultured fibroblasts.
AB  - The mechanism underlying the dermatological manifestations that accompany
      captopril therapy is not known. The facts that prolidase plays an important role
      in collagen biosynthesis and that captopril directly inhibits prolidase activity
      led us to evaluate its effect on collagen biosynthesis in cultured human skin
      fibroblasts. Confluent fibroblasts were treated with milimolar concentrations
      (0.2-1 mM) of captopril (CAP) for 48 h. It was found that CAP-dependent decrease
      in prolidase activity was accompanied by parallel decrease in collagen
      biosynthesis. Since insulin-like growth factor receptor (IGF-IR) is the most
      potent regulator of both collagen biosynthesis and prolidase activity, and
      prolidase is regulated by beta1 integrin signaling, the effect of CAP on IGF-IR
      and beta1 integrin receptor expressions was evaluated. It was found that exposure
      of the cells to 0.3 mM CAP contributed to a decrease in IGF-IR, alpha2beta1
      integrin receptor and MAPK/ERK1/2 expressions. The data suggest that CAP
      dependent decrease of collagen biosynthesis in cultured human skin fibroblasts
      results from inhibition of prolidase activity that may occur through inhibition
      of alpha2beta1 integrin and IGF-IR signaling.

PMID- 20824964
TI  - Bioactive compounds produced by clones of Rhodiola rosea maintained in the
      Norwegian germplasm collection.
AB  - Roseroot, Rhodiola rosea, is a perennial herbaceous plant of the family
      Crassulaceae. The rhizomes of 95 roseroot clones in the Norwegian germplasm
      collection were analysed and quantified for their content of the bioactive
      compounds rosavin, salidroside, rosin, cinnamyl alcohol and tyrosol using HPLC
      analysis. All five bioactive compounds were detected in all 95 roseroot clones
      but in highly variable quantities. The ranges observed for the different
      compounds were for rosavin 2.90-85.95 mg g(-1), salidroside 0.03-12.85 mg g(-1),
      rosin 0.08-4.75 mg g(-1), tyrosol 0.04-2.15 mg g(-1) and cinnamyl alcohol 0.02
      1.18 mg g(-1). The frequency distribution of the chemical content of each clone
      did not reflect a certain geographic region of origin or the gender of the plant.
      Significant correlations were found for the contents of several of these
      bioactive compounds in individual roseroot clones. A low, but not significant
      correlation was found between AFLP markers previously used to study the genetic
      diversity of the roseroot clones and their production of the chemical compounds.
      The maximum level of rosavin, rosin and salidroside observed were higher than for
      any roseroot plant previously reported in literature, and the roseroot clones
      characterized in this study might therefore prove to be of high pharmacological
      value.

PMID- 20824965
TI  - Platelet anti-aggregatory and blood anti-coagulant effects of compounds isolated
      from Paeonia lactiflora and Paeonia suffruticosa.
AB  - The roots of two Paeoniaceae family members have long been used as traditional
      medicines in Korea, China, and Japan. Dry roots of Paeonia lactiflora and dry
      root bark of P. suffruticosa are used under the traditional names of Paeoniae
      Radix and Moutan Cortex, respectively. Both Paeoniae Radix and Moutan Cortex have
      been used as remedies for cardiovascular diseases, for improving blood
      circulation, or for other uses. It was postulated that both plants may contain
      common active constituents that contribute to inhibiting blood coagulation and/or
      platelet aggregation. Eighteen compounds, which have been reported to be present
      in both plant medicines, were evaluated for their effects on platelet aggregation
      and blood coagulation. Paeonol (5), paeoniflorin (9), benzoylpaeoniflorin (11),
      and benzoyloxypaeoniflorin (12) were found to be the major common active
      constituents and they would collectively contribute to improving blood
      circulation through their inhibitory effects on both platelet aggregation and
      blood coagulation. In addition, methylgallate (4), (+)-catechin (7),
      paeoniflorigenone (8), galloylpaeoniflorin (13), and daucosterol (16) may also
      take part in improving blood circulation by inhibiting ether platelet aggregation
      and/or blood coagulation.

PMID- 20824966
TI  - [Treatment of unilateral vocal cord paralysis].
AB  - Unilateral vocal cord paralysis refers to the immobility or limitation of
      mobility of a vocal cord due to neural injury. Neural injury is most commonly
      caused by surgical trauma or a malignant tumor. Hoarseness with various degrees
      is the main symptom. The typical finding is a vocal cord remaining in a laterally
      immobile position on the side of injury in mirror examination, when the patient
      is asked to produce a voice. Establishing the etiology of the paralysis often
      requires imaging studies in order to exclude a tumor. Treatment consists of voice
      therapy and, in severe cases, voice surgery.

PMID- 20824967
TI  - [Psychiatric comorbidity in bipolar disorders].
AB  - Comorbid disorders such as anxiety disorders, ADHD and substance-related
      disorders are common in bipolar patients. Comorbidity impairs the functional
      capacity, quality of life and prognosis in these patients. Psychiatric drug
      treatments of comorbid disorders are challenging as they may induce rapid-cycling
      and mania, thus worsening the outcome. Generally, the therapeutic requirements of
      the most severe disorders, i.e. bipolar disorder, are prioritized. In some cases
      the drug treatments of comorbid disorders are justified only after optimizing the
      therapy of bipolar disorder.

PMID- 20824968
TI  - [Therapeutic lines for external injuries of the larynx in adults].
AB  - Injuries of the larynx are rare, and generally approved and consistent clinical
      guidelines are lacking. Depending on the mechanism, such an injury is either
      blunt or penetrating. This kind of injury may cause airway obstruction even with
      a delay of several hours. It is of principal importance to know when to suspect
      structural damage of the larynx, and to secure the airway. Laryngoscopy with a
      mirror or a flexible laryngoscope forms the basis for clinical examination, often
      complemented with computed tomography of the neck. Minor injuries of the larynx
      are treated conservatively and dislocated fractures surgically.

PMID- 20824969
TI  - [Work community--a threat and support to mental health].
AB  - The absolute and relative amount of employees who have disability pensions due to
      mental disorders has increased over the last few decades. During the last ten
      years, both disability pensions and absences due to sickness have increased about
      1.5-fold. The significance of a good work environment and community to an
      employee's mental health is and has been widely studied. Many of these studies
      have shown that poor organization and problems with social relationships and
      management at work may increase the probability of mental disorders. At the same
      time, a positive environment and atmosphere at work with suitable challenges for
      the employees can motivate them to commit to their work. This can increase the
      employees willingness to continue working until the proper retirement age and
      promote mental health.

PMID- 20824970
TI  - [Microhemorrhages in the brain. A magnetic resonance imaging finding with
      emerging significance].
AB  - Microhemorrhages in the brain refer to minor chronic hemorrhages that are
      revealed by specific magnetic imaging techniques. Whereas microhemorrhages in the
      brain are a common finding in patients with a disorder of the cerebral
      circulation, they are surprisingly often found also in elderly persons who are
      considered healthy. Microhemorrhages can be regarded as a biomarker of cerebral
      microangiopathy. They may also offer additional diagnostic information, provide
      clues for the prognosis of brain diseases, and influence clinical decisions. The
      patient's medical history, the location, number and distribution of imaging
      findings have a central role in the assessment of clinical significance.

PMID- 20824971
TI  - [Chronic back pain, hepatomegaly and dyspnea].
AB  - A 57-year-old male had suffered from back pain for years. Three years before the
      presenting symptoms he had had a lumbar disc operation during which he had bled
      markedly. Current symptoms of tiredness and dyspnea were new to this otherwise
      healthy and active man. Initial examinations revealed an enlarged liver, some
      ascites and signs of heart failure. A liver biopsy showed well-preserved
      structures with minor signs of inflammation. Cardiac cathetrization revealed
      increased pulmonary pressures and thus portopulmonary hypertension was suspected.
      A clinical examination, however, revealed a thrill and a strong systodiastolic
      murmur in the lower abdomen. CT-angiography confirmed the suspicion of an
      arteriovenous fistula. The fistula was successfully treated with a covered stent
      placed in the common iliac artery.

PMID- 20824972
TI  - [Mystery of the swollen leg].
AB  - This case report demonstrates a 90-year-old female patient who had an amelanotic
      subungual melanoma of the right hallux. As usual non healing ulcer of the nail
      bed was initially misdiagnosed. Finally melanoma spread to the groin lymph nodes
      and induced lymphedema of the leg leading to the right diagnosis. Acral lesion
      requires early biopsy if any clinical uncertainty exists.

PMID- 20824973
TI  - Is Vibrio fluvialis emerging as a pathogen with epidemic potential in coastal
      region of eastern India following cyclone Aila?
AB  - An isolated area with diarrhoea epidemic was explored at Pakhirala village of the
      Sundarbans, a coastal region of South 24 Parganas district of West Bengal,
      eastern India. The Pakhirala village was surrounded by other villages affected by
      a similar epidemic. The affected villages experienced this epidemic following the
      cyclone Aila, which had hit the coastal region of the Sundarbans in eastern
      India. In Pakhirala, the situation was the worst. Within a span of six weeks (5
      June-20 July 2009), 3,529 (91.2%) of 3,871 residents were affected by watery
      diarrhoea. Of all the cases (n = 3,529), 918 (26%) were affected by moderate to
      severe diarrhoea. In other villages, 28,550 (70%) of the 40,786 people were
      affected; of them, 3,997 (14%) had moderate to severe watery diarrhoea. The
      attack rate and the severity of the cases were significantly higher in Pakhirala
      village compared to other affected villages. The laboratory results revealed that
      Vibrio fluvialis was the predominant pathogen in Pakhirala village (5 of 6
      laboratory-confirmed organisms) whereas Vibrio cholerae O1 Ogawa was the
      predominant pathogen in other villages of Gosaba block (7 of 9 bacteriologically
      confirmed organisms). This result indicates that V fluvialis behaves more
      aggressively than V cholerae O1 in an epidemic situation with a higher attack
      rate and a different clinical picture. An in-depth study is required to explore
      its pathogenicity in detail, geographical distribution, and possible control
      measures, including development of specific vaccine preparation and determination
      of its efficacy.

PMID- 20824974
TI  - Bacterial bloodstream infections in HIV-infected adults attending a Lagos
      teaching hospital.
AB  - An investigation was carried out during October 2005-September 2006 to determine
      the prevalence of bloodstream infections in patients attending the outpatient
      department of the HIV/AIDS clinic at the Lagos University Teaching Hospital in
      Nigeria. Two hundred and one patients--86 males and 115 females--aged 14-65 years
      were recruited for the study. Serological diagnosis was carried out on them to
      confirm their HIV status. Their CD4 counts were done using the micromagnetic bead
      method. Twenty mL of venous blood sample collected from each patient was
      inoculated into a pair of Oxoid Signal blood culture bottles for 2-14 days.
      Thereafter, 0.1 mL of the sample was plated in duplicates on MacConkey, blood and
      chocolate agar media and incubated at 37 degrees C for 18-24 hours. The CD4+
      counts were generally low as 67% of 140 patients sampled had < 200 cells/microL
      of blood. Twenty-six bacterial isolates were obtained from the blood samples and
      comprised 15 (58%) coagulase-negative staphylococci as follows: Staphylococcus
      epidermidis (7), S. cohnii cohnii (1), S. cohnii urealyticum (2), S. chromogenes
      (1), S. warneri (2), S. scuri (1), and S. xylosus (1). Others were 6 (23%) Gram
      negative non-typhoid Salmonella spp., S. Typhimurium (4), S. Enteritidis (2);
      Pseudomonas fluorescens (1), Escherichia coli (1), Ochrobactrum anthropi (1),
      Moraxella sp. (1), and Chryseobacterium meningosepticum. Results of antimicrobial
      susceptibility tests showed that coagulase-negative staphylococci had good
      sensitivities to vancomycin and most other antibiotics screened but were
      resistant mainly to ampicilin and tetracycline. The Gram-negative organisms
      isolated also showed resistance to ampicillin, tetracycline, chloramphenicol, and
      septrin. This study demonstrates that coagulase-negative staphylococci and non
      typhoidal Salmonellae are the most common aetiological agents of bacteraemia
      among HIV-infected adults attending the Lagos University Teaching Hospital,
      Nigeria. The organisms were resistant to older-generation antibiotics often
      prescribed in this environment but were sensitive to vancomycin, cefotaxime,
      cefuroxime, and other new-generation antibiotics.

PMID- 20824975
TI  - Incidence and spread of Mycobacterium tuberculosis-associated infection among Aba
      Federal prison inmates in Nigeria.
AB  - The study was undertaken to determine transmission of Mycobacterium tuberculosis
      within the prison environment. In total, 168 Aba Federal prison inmates in
      Nigeria were evaluated for tuberculosis (TB) by sputum-smear microscopy and
      sputum culture, simultaneously, and for HIV status by serology. They were
      subsequently followed up for one year for fresh Mycobacterium-associated
      infection by tuberculin skin testing or for development of TB and for HIV
      infection or AIDS. Ninety-one (54.2%) of the 168 prison inmates had infection due
      to Mycobacterium, and three (3.3%) of them were sputum-smear- and culture
      positive while 41 (24.4%), including one (2.4%) with concomitant TB, were HIV
      infected. In a one-year follow-up study, 11 (19.3%) of 57 tuberculin skin test
      (TST)- and HIV-negative inmates became TST-positive and one (1.8%) HIV-positive,
      eight (13.8%) of the 58 TST-positive but HIV-negative inmates developed TB, and
      one (1.7%) became HIV-infected: six (24.0%) of 25 TST- and HIV-positive inmates
      developed TB while five (33.3%) of 15 TST-negative but HIV-positive inmates
      became TST-positive, and one (6.7%) progressed to AIDS. The duration of
      imprisonment did not influence the rates of infection, and the transmission of
      Mycobacterium tuberculosis did not necessarily require sharing a cell with a TB
      case.

PMID- 20824976
TI  - Effect of dietary fat supplementation during late pregnancy and first six months
      of lactation on maternal and infant vitamin A status in rural Bangladesh.
AB  - Dietary fat intake is extremely low in most communities with vitamin A
      deficiency. However, its role in vitamin A status of pregnant and lactating women
      is poorly understood. The aim of the study was to examine the effect of
      supplementing women with fat from mid-/late pregnancy until six months postpartum
      on their vitamin A status and that of their infants. Women recruited at 5-7
      months of gestation were supplemented daily with 20 mL of soybean-oil (n = 248)
      until six months postpartum or received no supplement (n = 251). Dietary fat
      intake was assessed by 24-hour dietary recall at enrollment and at 1, 3 and 6
      months postpartum. Concentrations of maternal plasma retinol, beta-carotene, and
      lutein were measured at enrollment and at 1, 3 and 6 months postpartum, and those
      of infants at six months postpartum. Concentration of breastmilk retinol was
      measured at 1, 3 and 6 months postpartum. The change in concentration of plasma
      retinol at three months postpartum compared to pregnancy was significantly higher
      in the supplemented compared to the control women (+0.04 vs -0.07 micromol/L
      respectively; p < 0.05). Concentrations of plasma beta-carotene and lutein
      declined in both the groups during the postpartum period but the decline was
      significantly less in the supplemented than in the control women at one month
      (beta-carotene -0.07 vs -0.13 micromol/L, p < 0.05); lutein -0.26 vs -0.49
      micromol/L, p < 0.05) and three months (beta-carotene -0.04 vs -0.08 micromol/L,
      p < 0.05; lutein -0.31 vs -0.47 micromol/L, p < 0.05). Concentration of
      breastmilk retinol was also significantly greater in the supplemented group at
      three months postpartum than in the controls (0.68 +/- 0.35 vs 0.55 +/- 0.34
      micromol/L respectively, p < 0.03). Concentrations of infants' plasma retinol,
      beta-carotene, and lutein, measured at six months of age, did not differ between
      the groups. Fat supplementation during pregnancy and lactation in women with a
      very low intake of dietary fat has beneficial effects on maternal postpartum
      vitamin A status.

PMID- 20824977
TI  - Maternal and neonatal serum zinc level and its relationship with neural tube
      defects.
AB  - Neural tube defect (NTD) is a multi-factorial disorder in which nutritional,
      genetic and environmental factors are involved. Among the nutritional factors,
      low level of serum zinc has been reported from different parts of the world. This
      hospital-based case-control study was conducted with the objective of finding the
      relationship between serum zinc level in newborns and their mothers and NTDs in a
      Bangladeshi population. The study was conducted during August 2006-July 2007 at
      the Bangabandhu Sheikh Mujib Medical University (BSMMU) in Dhaka. In total, 32
      mothers and their newborns with NTDs were included as cases and another 32
      mothers with their normal babies were included as controls. Concentration of
      serum zinc was determined by pyro-coated graphite furnace atomic absorption
      spectrophotometer (GF-AAS). The mean age of the case and control mothers was
      25.28 years and 24.34 years respectively. The mean gestational age of the case
      newborns was 36.59 weeks and that of the control newborns was 37.75 weeks. The
      mean serum zinc level of the case and control mothers was 610.2 microg/L and
      883.0 microg/L respectively (p < 0.01). The mean serum zinc level of the case and
      control newborns was 723 microg/L and 1,046 microg/L respectively (p < 0.01). In
      both case and control groups, the serum zinc level of the newborns positively
      correlated with that of the mothers. The serum zinc levels of the mothers and
      newborns negatively correlated with NTDs. Mothers with serum zinc level lower
      than normal were 7.66 [95% confidence interval (CI) 2.5-23.28] times more likely
      to have NTDs compared to the normal zinc level of mothers. After adjusting for
      the zinc level of the newborns, parity, and age of the mothers, this risk reduced
      1.61 times [confidence interval (CI) 95% 0.24-8.77]. On the other hand, the low
      serum zinc level of the newborns was 7.22 times more associated with NTDs
      compared to the newborns with the normal serum zinc level, which was
      statistically significant (p = 0.001). After adjusting for other factors, such as
      maternal age and parity, newborns with the low serum zinc level was found to be
      9.186 times more likely to be associated with NTDs compared to newborns with
      normal serum zinc level. Based on the findings, it may be concluded that the low
      serum zinc levels of newborns may be associated with NTDs. To confirm these
      findings, a further study with a larger sample-size is recommended. Moreover, a
      follow-up study with zinc supplementation to pregnant women and its impact on
      NTDs is also recommended.

PMID- 20824978
TI  - Prevalence of goitre in Isfahan, Iran, fifteen years after initiation of
      universal salt iodization.
AB  - This cross-sectional study investigated the prevalence of goitre in Isfahan, a
      centrally-located city in Iran, 15 years after the initiation of universal salt
      iodization. In total, 2,523 Isfahani adults (1,275 males, 1,248 females) aged >
      20 years were selected by multi-stage cluster-sampling method. Goitre rate, serum
      thyroid-stimulating hormone (TSH), thyroxine (T4), thyroid peroxidase antibody
      (TPOAb), thyroglobulin antibody (TgAb), and urinary iodine concentration (UIC)
      were measured and compared between the goitrous (n = 478) and the non-goitrous (n
      = 2,045) participants. The total goitre rate was 19% (n = 478) of the 2,523
      adults. The rate of Grade I and II goitre was 12.4% (n = 312) and 6.6% (n = 166)
      respectively. The total goitre rate, Grade I and II goitre were more prevalent
      among women than among men. Hypothyroidism was observed in 6.4% (130/2,045) and
      18.6% (89/478) of the non-goitrous and goitrous participants respectively [odds
      ratio (OR) = 3.6, 95% confidence interval (CI) 2.7-4.9, p = 0.001].
      Hyperthyroidism was present in 0.8% (17/2,045) and 5.2% (29/478) of the non
      goitrous and goitrous adults respectively (OR = 9.0, 95% CI 4.9-16.6, p = 0.001).
      Hypothyroidism was more prevalent in Grade II than in Grade I goitre and among
      those without goitre (31.3%, 14.1%, and 6.4% respectively) (p = 0.001). Positive
      TPOAb was observed in 24% (n = 50) of the non-goitrous and 33.5% (n = 84) of the
      goitrous subjects (p = 0.03). Positive TPOAb was observed in 24.6% (35 of 142) of
      the Grade I and 45% (49 of 109) of the Grade II goitrous adults (p = 0.001).
      Positive TgAb was observed in 21.6% (n = 45) of the non-goitrous and 35.9% (n =
      90) of the goitrous adults (p = 0.001). Positive TgAb was observed in 30.3% (43
      of 142) of the Grade I and 43.1% (47 of 109) of the Grade II goitrous adults (p =
      0.04). The median UIC was 18 microg/dL (range 1-80 microg/dL). It was 17.9
      microg/dL and 19 microg/dL in the non-goitrous and goitrous adults respectively.
      After 15 years of successful universal salt iodization in Isfahan, goitre is
      still endemic, which may be due to thyroid autoimmunity. However, other
      environmental or genetic factors may have a role.

PMID- 20824979
TI  - Prevalence of anaemia, deficiencies of iron and folic acid and their determinants
      in Ethiopian women.
AB  - A cross-sectional community-based study with analytic component was conducted
      among Ethiopian women during June-July 2005 to assess the magnitude of anaemia
      and deficiencies of iron and folic acid and to compare the factors responsible
      for anaemia among anaemic and non-anaemic cases. In total, 970 women, aged 15-19
      years, were selected systematically for haematological and other important
      parameters. The overall prevalence of anaemia, iron deficiency, iron-deficiency
      anaemia, deficiency of folic acid, and parasitic infestations was 30.4%, 50.1%,
      18.1%, 31.3%, and 13.7% respectively. Women who had more children aged less than
      five years but above two years, open-field toilet habits, chronic illnesses, and
      having intestinal parasites were positively associated with anaemia. Women who
      had no formal education and who did not use contraceptives were negatively
      associated with anaemia. The major determinants identified for anaemia were
      chronic illnesses [adjusted odds ratio (AOR) = 1.1, 95% confidence interval (CI)
      1.15-1.55), deficiency of iron (AOR = 0.4, 95% CI 0.35-0.64), and deficiency of
      folic acid (AOR = 0.5, 95% CI 0.50-0.90). The odds for developing anaemia was 1.1
      times more likely among women with chronic illnesses, 60% more likely in the iron
      deficient and 40% more likely in the folic acid-deficient than their
      counterparts. One in every three women had anaemia and deficiency of folic acid
      while one in every two had iron deficiency, suggesting that deficiencies of both
      folic acid and iron constitute the major micronutrient deficiencies in Ethiopian
      women. The risk imposed by anaemia to the health of women ranging from impediment
      of daily activities and poor pregnancy outcome calls for effective public-health
      measures, such as improved nutrient supplementation, health education, and timely
      treatment of illnesses.

PMID- 20824980
TI  - Limited access to iodized salt among the poor and disadvantaged in North 24
      Parganas district of West Bengal, India.
AB  - Iodine deficiency is endemic in West Bengal as evident from earlier studies. This
      community-based, cross-sectional descriptive study was conducted in North 24
      Parganas district during August-November 2005 to assess the consumption of
      adequately-iodized salt and to ascertain the various factors that influence
      access to iodized salt. In total, 506 households selected using the multi-stage
      cluster-sampling technique and all 79 retail shops from where the study
      households buy salt were surveyed. The iodine content of salt was tested by spot
      iodine-testing kits. Seventy-three percent of the households consumed salt with
      adequate iodine content (> or = 15 ppm). Consumption of adequately-iodized salt
      was lower among rural residents [prevalence ratio (PR): 0.8, 95% confidence
      interval (CI) 0.7-0.9], Muslims (PR: 0.8, 95% CI 0.7-0.9), and households with
      monthly per-capita income of < or = US$ 10 (PR: 0.7, 95% CI 0.6-0.8). Those who
      heard and were aware of the risk of iodine-deficiency disorders and of the
      benefit of iodized salt were more likely to use appropriate salt (PR: 1.2, 95% CI
      1.1-1.3). Those who were aware of the ban on non-iodized salt were more likely to
      consume adequately-iodized salt (PR: 1.1, 95% CI 1.01-1.3). The iodine content
      was higher in salt sold in sealed packets (PR: 2.9, 95% CI 1.8-4.8) and stored on
      shelves (PR: 1.6, 95% CI 1.3-2.0). Seventy-two percent of the salt samples from
      the retail shops had the iodine content of > or = 15 ppm. The findings indicate
      that elimination of iodine deficiency will require targeting the vulnerable and
      poor population.

PMID- 20824981
TI  - Causes of neonatal deaths in a rural subdistrict of Bangladesh: implications for
      intervention.
AB  - The study assessed the timing and causes of neonatal deaths in a rural area of
      Bangladesh. A population-based demographic surveillance system, run by the
      International Centre for Diarrhoeal Disease Research, Bangladesh, recorded
      livebirths and neonatal deaths during 2003-2004 among a population of 224,000
      living in Matlab, a rural subdistrict of eastern Bangladesh. Deaths were
      investigated using the INDEPTH/ World Health Organization verbal autopsy. Three
      physicians independently reviewed data from verbal autopsy interview to assign
      the cause of death. There were 11,291 livebirths and 365 neonatal deaths during
      the two-year period. The neonatal mortality rate was 32.3 per 1,000 livebirths.
      Thirty-seven percent of the neonatal deaths occurred within 24 hours, 76% within
      0-3 days, 84% within 0-7 days, and the remaining 16% within 8-28 days. Birth
      asphyxia (45%), prematurity/low birthweight (15%), sepsis/meningitis (12%),
      respiratory distress syndrome (7%), and pneumonia (6%) were the major direct
      causes of death. Birth asphyxia (52.8%) was the single largest category of cause
      of death in the early neonatal period while meningitis/sepsis (48.3%) was the
      single largest category in the late neonatal period. The high proportion of
      deaths during the early neonatal period and the far-higher proportion of neonatal
      deaths caused by birth asphyxia compared to the global average (45% vs 23-29%)
      indicate the lack of skilled birth attendance and newborn care for the large
      majority of births that occur in the home in rural Bangladesh. Resuscitation of
      newborns and management of low-birthweight/premature babies need to be at the
      core of neonatal interventional packages in rural Bangladesh.

PMID- 20824982
TI  - Birth preparedness and complication readiness among slum women in Indore city,
      India.
AB  - Three hundred twelve mothers of infants aged 2-4 months in 11 slums of Indore,
      India, were interviewed to assess birth preparedness and complication readiness
      (BPACR) among them. The mothers were asked whether they followed the desired four
      steps while pregnant: identified a trained birth attendant, identified a health
      facility, arranged for transport, and saved money for emergency. Taking at least
      three steps was considered being well-prepared. Taking two or less steps was
      considered being less-prepared. One hundred forty-nine mothers (47.8%) were well
      prepared. Factors associated with well-preparedness were assessed using adjusted
      multivariate models. Factors associated with well-preparedness were maternal
      literacy [odds ratio (OR) = 1.9, (95%) confidence interval (CI) 1.1-3.4] and
      availing of antenatal services (OR = 1.7, CI 1.05-2.8). Deliveries in the slum
      home were high (56.4%). Among these, skilled attendance was low (7.4%); 77.3% of
      them were assisted by traditional birth attendants. Skilled attendance during
      delivery was three times higher in well-prepared mothers compared to less
      prepared mothers (OR: 3.0, CI 1.6-5.4) Antenatal outreach sessions can be used
      for promoting BPACR. It will be important to increase the competency of slum
      based traditional birth attendants, along with promoting institutional
      deliveries.

PMID- 20824983
TI  - Childhood injuries in Pakistan: results from two communities.
AB  - The study aimed at determining the incidence, nature, and extent of childhood
      injuries in two suburban and rural communities of Pakistan. The findings of the
      study are based on a cross-sectional survey of 2,292 children aged 1-8 years.
      Information was sought retrospectively from the primary caregiver on the
      occurrence of injury that required formal or informal medical consultation during
      the past three months. The incidence rate of non-fatal injuries that required
      care outside home for children aged 1-8 years was 19.7 injuries per 100 person
      (child)-years of exposure [95% confidence interval (CI) 16.41-23.51]: 26.5
      injuries per 100 person (child)-years of exposure (95% CI 21.31-32.63) in the
      suburban area and 12.1 injuries per 100 person (child)-years of exposure (95% CI
      8.68-16.66) in the rural area. The most common non-fatal injuries were falls
      (10.5 fall injuries per 100 person (child)-years of exposure), bums and scalds
      (3.5 burn injuries per 100 person (child)-years of exposure), and road traffic
      injuries (RTIs) (2 RTIs per 100 person (child)-years of exposure). One fatality
      due to drowning was also reported during the study period. The difference among
      sex was highly significant (p = 0.03). Boys (60%) were at a higher risk of
      injuries compared to girls (40%). The data also revealed that 61% of the injuries
      took place inside the home. The magnitude of childhood injuries in the two
      communities was significant compared to the findings of the National Health
      Survey of Pakistan (1990-1994). The fact that the majority (61%) of the injuries
      occurred inside the home raises many questions in relation to the household
      hazards and adequacy of safety and child-proofing measures in these households.
      There is a need to develop community-based interventions, creating awareness
      about the consequences of childhood injuries and educating families about
      preventive measures to reduce the incidence of injuries during early and middle
      childhood.

PMID- 20824984
TI  - Causes for hospitalizations at upazila health complexes in Bangladesh.
AB  - Morbidity and mortality data are important for planning and implementing
      healthcare strategies of a country. To understand the major causes for
      hospitalizations in rural Bangladesh, demographic and clinical data were
      collected from the hospital-records of five government-run rural health
      facilities (upazila health complexes) situated at different geographical regions
      of the country from January 1997 to December 2001. During this period, 75,598
      hospital admissions in total were recorded, of which 54% were for male, and 46%
      were for female. Of all the admissions, diarrhoeal disease was the leading cause
      for hospitalization (25.1%), followed by injuries (17.7%), respiratory tract
      diseases (12.6%), diseases of the gastrointestinal tract (10.5%), obstetric and
      gynaecological causes (8.5%), and febrile illnesses (6.7%). A considerable
      proportion (8.3%) of the hospitalized patients remained undiagnosed. Despite the
      limitations of hospital-based data, this paper gives a reasonable insight of the
      important causes for hospitalizations in upazila health complexes that may guide
      the policy-makers in strengthening and prioritizing the healthcare needs at the
      upazila level in Bangladesh.

PMID- 20824985
TI  - Understanding below-replacement fertility in Kerala, India.
AB  - Kerala is well-known globally for the unprecedented fertility transition in the
      Indian subcontinent towards the end of the last century. The state has already
      reached below-replacement fertility level in the 1990s while the rest of India
      was experiencing high or mid-level fertility. With this backdrop, an attempt was
      made in this paper (a) to explore the plausible factors associated with sub
      replacement fertility and consequent population momentum in Kerala and (b) to
      trace their socioeconomic and health policy implications. The underlying factors
      that led to the fertility transition was explored and discussed in some detail.
      An enhanced level of human development achieved during the last quarter of the
      20th century mainly through developments in social and health sectors, is likely
      to be the main contributor. Unlike other states in India, there were historical
      factors as well that functioned as a catalyst for this, such as widespread
      education and women's empowerment. As an inevitable demographic impact,
      population growth due to momentum is expected to be very strong in Kerala with an
      age-structural transition favouring the old. The so-called 'demographic dividend'
      invoked by the increase of labour-force derived from the youth bulge in the age
      structure is being lost in the state due to very limited capital investments and
      political will. Again, as a direct consequence of population growth, population
      density in Kerala will take a staggering level of 1,101 persons per sq km in
      2026. The ill effects of environmental deterioration and consequent changes in
      morbidity patterns will have to be dealt with seriously. The very foundations of
      health policy needs revamping in the light of demographic changes associated with
      sub-replacement fertility. The tempo of population-ageing is very high in Kerala.
      The proportion of population aged 60+ years is likely to be 20% in 2026 whereas
      it will be around 12% only in India. The current level of social and health
      infrastructure in the state may not be sufficient to cope with the emerging
      demands of population-ageing since the financial and morbidity burdens of the
      elderly are already quite high. To conclude, Kerala portrays a typical case of
      the vagaries of the onset of sub-replacement fertility level in the absence of
      reasonable structural changes in the economic and health fronts.

PMID- 20824986
TI  - Hartnup disease masked by kwashiorkor.
AB  - This report describes an 11-month old girl with Hartnup disease presenting with
      kwashiorkor and acrodermatitis enteropathica-like skin lesions but free of other
      clinical findings. This case with kwashiorkor had acrodermatitis enteropathica
      like desquamative skin eruption. Since zinc level was in the normal range,
      investigation for a metabolic disorder was considered, and Hartnup disease was
      diagnosed.

PMID- 20824987
TI  - Cognitive demand of human sensorimotor performance during an extended space
      mission: a dual-task study.
AB  - INTRODUCTION: Two previous single-case studies found that the dual-task costs of
      manual tracking plus memory search increased during a space mission, and
      concluded that sensorimotor deficits during spaceflight may be related to
      cognitive overload. Since dual-task costs were insensitive to the difficulty of
      memory search, the authors argued that the overload may reflect stress-related
      problems of multitasking, rather than a scarcity of specific cognitive resources.
      Here we expand the available database and compare different types of concurrent
      task. METHODS: Three subjects were repeatedly tested before, during, and after an
      extended mission on the International Space Station (ISS). They performed an
      unstable tracking task and four reaction-time tasks, both separately and
      concurrently. Inflight data could only be obtained during later parts of the
      mission. RESULTS: The tracking error increased from pre- to in flight by a factor
      of about 2, both under single- and dual-task conditions. The dual-task costs with
      a reaction-time task requiring rhythm production was 2.4 times higher than with a
      reaction-time task requiring visuo-spatial transformations, and 8 times higher
      than with a regular choice reaction-time task. CONCLUSIONS: Long-term
      sensorimotor deficits during spaceflight may reflect not only stress, but also a
      scarcity of resources related to complex motor programming; possibly those
      resources are tied up by sensorimotor adaptation to the space environment.

PMID- 20824988
TI  - Prediction of resultant testosterone concentrations from flywheel-based resistive
      exercise.
AB  - INTRODUCTION: Numerous variables impact resultant testosterone concentrations
      (TC) that foretell the efficacy of workouts. Identifying variables may aid the
      development of in-flight exercise prescription. METHODS: To identify variables
      that predict the variance in TC from flywheel ergometer exercise, 17 subjects did
      3 workouts in a randomized order. Comprised of 10-repetition leg press sets,
      workouts entailed either: 1) 3 sets of both concentric and eccentric muscle
      actions (CE3), and concentric-only actions done for 2) three (CO3), or 3) six
      (CO6) sets. Venous plasma TC were collected before and at 1 and 30 min
      postexercise. The last two collection points served as criterion measures. Body
      mass, delta blood lactate levels, peak angular velocity, average power, and total
      work from workouts were used to predict the variance in TC. RESULTS: Predictor
      variables accounted for significant levels of variance at both 1 and 30 min post
      exercise for both the CE3 and the concentric-only (CO3 and CO6 bouts combined)
      workouts using multivariate regression. Inclusion of eccentric variables (only
      collected from the CE3 bout; r2 = 0.90) predicted nearly twice the variance than
      the concentric-only (r2 = 0.54) workouts. CONCLUSIONS: Body mass and average
      power indices were the best predictors of the variance in post-workout TC. Since
      a flywheel-based device is used to abate in-flight muscle atrophy and strength
      losses, exercise prescriptions may wish to monitor these indices as they impacted
      post-workout TC to the greatest extent. Future research should assess why
      eccentric variables increased the amount of explained variance from flywheel
      ergometer workouts.

PMID- 20824989
TI  - Oculomotor measures as predictors of performance during sleep deprivation.
AB  - INTRODUCTION: Studies have indicated that working under sleep deprivation
      conditions results in deficits in performance on various tasks. Few studies,
      however, have attempted to find a measure for predicting performance changes
      under sleep deprivation conditions. The current study examined whether oculomotor
      measures could predict changes in performance under non-sleep deprivation and
      acute short-term sleep deprivation conditions. METHODS: Oculomotor measures and
      performance were examined during five testing sessions in each study. In the non
      sleep deprivation study (N = 23) the testing sessions took place during 2
      consecutive days. The sleep deprivation study (N = 26) took place in an 18-h
      sustained operations period during the night of sleep deprivation. RESULTS: Under
      non-sleep deprivation conditions, pupil diameter significantly predicted
      performance on grammatical reasoning (B = 0.360) and constriction latency
      significantly predicted performance on combined tasks (B = 0.182). Under sleep
      deprivation conditions, diameter, constriction latency, and saccadic velocity
      significantly predicted performance on a psychomotor vigilance task (B = -21.002,
      B = -23.126, B = -18.028, respectively). Overall, oculomotor measures better
      predicted performance changes under sleep deprivation conditions and better
      predicted performance decrements on vigilance-based tasks than cognitive tasks
      under acute sleep deprivation conditions. DISCUSSION: The current research
      suggests saccadic velocity and pupil diameter may be the most useful predictors
      of performance under sleep deprivation conditions, perhaps because these measures
      are largely controlled by involuntary neural components that slow during sleep
      deprivation. These data support research suggesting that saccadic velocity and
      pupil diameter detect excessive sleepiness and predict performance decrements
      under sleep deprivation conditions using additional oculomotor measures and a non
      sleep deprivation comparison group.

PMID- 20824990
TI  - Postural activity and visual vigilance performance during rough seas.
AB  - BACKGROUND: Motion of a ship at sea often challenges crew performance. In
      previous studies, the influence of rough weather on stance at sea has been
      evaluated in terms of the likelihood of staggers or falls. Few studies have
      evaluated the influence of sea state on visual performance. Effects of rough seas
      on visual vigilance performance, subjective mental workload, and the kinematics
      of postural control have not been demonstrated. METHOD: Crewmembers of the R/V
      Thomas G. Thompson stood on a force plate, from which we obtained data on the
      center of pressure (COP). We varied stance width (the distance between the feet
      in side-by-side stance; 5 cm, 17 cm, and 30 cm) and the difficulty of visual
      vigilance tasks (Easy vs. Hard). Separately, we evaluated subjects' self-selected
      foot positioning. RESULTS: Visual performance was better on the Easy task (mean
      d' = 4.20) than on the Hard task (mean d' = 3.57). Overall vigilance performance
      (mean d' = 3.88) was worse than when the same subjects were tested under mild sea
      states (mean d' = 4.11). Subjective mental workload (mean = 28.0) was greater
      than under mild sea states (mean = 19.9). Relative to mild sea states the
      variability of postural activity was greater and its predictability was reduced.
      In addition, postural dynamics were influenced by controlled variations in stance
      width. CONCLUSIONS: Rough seas affect visual vigilance performance and postural
      activity, but do not eliminate the effects of vigilance task difficulty or stance
      width that have been found in mild seas.

PMID- 20824991
TI  - Aircraft type and other risk factors for spinal disorders: data from 19,673
      military cockpit aircrew.
AB  - INTRODUCTION: Many assume that exposure to flight in high-performance aircraft
      (HPA) or rotary wing aircraft (RWA) increases the risk of spinal disorders
      compared to other fixed wing aircraft (FWA). However, this association has yet to
      be confirmed. This study explores the relationship between flight in different
      aircraft and the development of lumbar and cervical spine disorders. METHODS: The
      flight records of 19,673 U.S. Air Force (USAF) cockpit aircrew officers were
      examined for entries with a spinal disorder diagnosis in an existing aircrew
      health information database. Univariate and multivariate analyses were employed
      to examine the association between aircraft type, other variables, and spinal
      disorders. RESULTS: In stratified analysis of HPA and FWA, but not RWA
      categories, statistically significant unadjusted associations were observed
      between flight hours and cervical [HPA: odds ratio (OR) = 2.80, FWA: OR = 4.73]
      and lumbar disorders (HPA: OR = 2.46, FWA: OR = 3.01). After adjustment for birth
      year in a stratified multivariate analysis, these associations were no longer
      statistically significant. In all three aircraft types, statistically significant
      adjusted associations were observed between older birth year category and both
      cervical (HPA: OR = 3.82, FWA: OR = 5.88) and lumbar disorders (HPA: OR = 4.16,
      RWA: OR = 2.96, FWA: OR = 2.39). DISCUSSION: The risk produced by exposure to
      HPA, RWA, or FWA as measured by flight hours may be overshadowed by that produced
      by birth year, which was the strongest predictor for spinal disorders in this
      study. Future endeavors should more closely examine the association between age
      and accrual of flight hours in various aircraft types in order to accurately
      direct preventive measures.

PMID- 20824992
TI  - Hypoxia awareness training for aircrew: a comparison of two techniques.
AB  - INTRODUCTION: Major hazards associated with hypoxia awareness training are the
      risks of decompression sickness, barotrauma, and loss of consciousness. An
      alternate method has been developed which combines exposure to a simulated
      altitude of 10,000 ft (3048 m) with breathing of a gas mixture containing 10%
      oxygen and 90% nitrogen. The paradigm, called Combined Altitude and Depleted
      Oxygen (CADO), places the subjects at a physiological altitude of 25,000 ft (7620
      m) and provides demonstration of symptoms of hypoxia and the effects of pressure
      change. CADO is theoretically safer than traditional training at a simulated
      altitude of 25,000 ft (7620 m) due to a much lower risk of decompression sickness
      (DCS) and has greater fidelity of training for fast jet aircrew (mask-on
      hypoxia). This study was conducted to validate CADO by comparing it with
      hypobaric hypoxia. METHODS: There were 43 subjects who were exposed to two
      regimens of hypoxia training: hypobaric hypoxia (HH) at a simulated altitude of
      25,000 ft (7620 m) and CADO. Subjective, physiological, and performance data of
      the subjects were collected, analyzed, and compared. RESULTS: There were no
      significant differences in the frequency and severity of the 24 commonly reported
      symptoms, or in the physiological response, between the two types of hypoxia
      exposure. CONCLUSIONS: CADO is similar to HH in terms of the type and severity of
      symptoms experienced by subjects, and appears to be an effective, useful, and
      safe tool for hypoxia training.

PMID- 20824993
TI  - Five-factor model facet characteristics of non-aeronautically adaptable military
      aviators.
AB  - BACKGROUND: The present study revisited a large sample of clinically referred
      military aviators, previously evaluated across factors of the Five Factor Model
      of personality (FFM), to determine whether identified facet differences were
      consistent with U.S. Navy guidelines for evaluating aeronautical adaptability.
      METHODS: Clinically evaluated U.S. Naval aviators and flight officers (N = 954)
      disposed as either aeronautically adaptable (AA) or not aeronautically adaptable
      (NAA) were compared with respect to their facet level scores on the NEO
      Personality Inventory (NEO PI-R). Additional analyses were conducted to control
      for NAA status attributable to physical as opposed to psychological standards and
      for student versus designated aviator/flight officer experience levels. RESULTS:
      NAA aviators and flight officers, when compared to their AA counterparts,
      evidenced significant and substantive effect size differences on facets measuring
      negative emotionality, interpersonal effectiveness, and goal-orientation.
      CONCLUSION: FFM facet differences between AA and NAA officers were only partially
      consistent with U.S. Navy guidelines; expected facet differences related to
      compliance, deliberation, actions, and excitement-seeking/impulsivity were not
      observed.

PMID- 20824994
TI  - Optical filter effects on night vision goggle acuity and preservation of dark
      adaptation.
AB  - INTRODUCTION: The high output of night vision goggles (NVGs) can cause a loss of
      dark adaptation, resulting in suboptimal unaided vision. Optical filters have
      been designed to mitigate this problem by changing the overall output
      characteristics of the NVGs. METHODS: Several aspects of visual performance
      related to NVG use were studied in a repeated measures design, filters versus no
      filters. NVG acuity was assessed using a 25% contrast chart, while preservation
      of dark adaptation after NVG use was measured with a scotopic sensitivity tester
      (SST) and a low luminance acuity chart. Testing was accomplished at two light
      levels, roughly corresponding to starlight and quarter moon conditions. RESULTS:
      Use of the filters resulted in a statistically significant loss of acuity of
      about a 1/2 line (approximately 2.5 letters) at both light levels. The second
      part of the study identified a 47% improvement in preservation of dark adaptation
      under simulated starlight conditions and a 31% improvement under simulated
      quarter moon conditions with filter use; however, only the starlight finding was
      statistically significant. No significant differences in performance were seen
      with the low luminance chart. DISCUSSION: Despite a small loss of visual acuity
      with filter use, the improvement in retention of dark adaptation may be
      beneficial in certain operational environments. Aviators, airmen, and commanders
      should evaluate how the potential for slightly poorer visual acuity and improved
      recovery of dark adapted vision relates to their mission specific requirements
      prior to implementing use of NVG filters.

PMID- 20824995
TI  - Altitude chamber related adverse effects among 1241 airmen.
AB  - INTRODUCTION: Altitude chambers are used for training aircrews, but incidents
      have been reported, including decompression sickness (DCS) and barotrauma. To
      minimize chamber-related adverse effects we implemented a set of measures,
      including altitude restriction and a pre-chamber clinical selection (PCS) of
      subjects before exposure. METHODS: We reviewed our records regarding 1254
      individuals who were trained from 2003 to 2009. After the first 3 subjects, the
      maximum altitude of the highest training profile was limited to 43,000 ft
      (13,106.4 m) instead of 45,000 ft (13,716 m) and, after the first 327 subjects, a
      clinical evaluation of each trainee was performed by an otolaryngologist before
      altitude exposure. The evaluation included otoscopy and tympanometry, and
      subjects with abnormal results were not cleared for altitude exposure. Subjects
      were grouped by having undergone the highest profile before (3 subjects) or after
      altitude restriction (8 subjects) and received clinical selection (PCS group, 927
      subjects) or not (control group, 327 subjects). RESULTS: We recorded 32 total
      adverse effects (overall incidence 2.6%), 21 in the PCS group (2.3%) and 11 in
      the control group (3.4%). The difference between groups was not significant.
      Adverse effects included 19 cases of acute barotitis (1.5%), 1 case of DCS
      (0.08%), and 4 cases of syncope (0.3%). The incidence of barotitis was 1.1% in
      the PCS group and 2.7% in the control group. The altitude restriction was
      ineffective in preventing both barotrauma and DCS. CONCLUSIONS: The incidence of
      adverse effects in our subjects was low and pre-chamber clinical selection
      appeared to be effective in reducing the risk of barotitis.

PMID- 20824996
TI  - Determination of normative neck muscle morphometry using upright MRI with
      comparison to supine data.
AB  - BACKGROUND: Neck muscles are important in the static and dynamic stability of the
      head-neck complex. Deep neck muscles act to maintain upright posture and
      superficial muscles are responsible for gross movements. Previous studies have
      quantified neck muscle geometry using traditional supine magnetic resonance
      imaging (MRI). However, supine orientation removes the vertical load on the
      cervical spine from the head-neck complex and changes the relative orientation of
      the spine and neck muscles. Therefore, the purpose of this study was to
      demonstrate the feasibility of upright MRI to obtain neck muscle morphometric
      data on a spinal level-by-level basis for subjects in upright seated positions.
      METHODS: Upright MRI scans were obtained of the neck region for six younger male
      volunteers in neutral and flexed positions. Planar images were oriented parallel
      to the intervertebral disc space at each level. Cross-sectional area (CSA) and
      orientation of neck muscles were quantified at four spinal levels. RESULTS: Area
      and position of all four muscles were significantly dependent upon spinal level.
      Average CSA of the sternocleidomastoid, longus colli, levator scapulae, and
      trapezius muscles in neutral position were 512, 113, 281, and 174 mm2. Head-neck
      position significantly affected area and position of the sternocleidomastoid and
      position of posterior neck muscles. DISCUSSION: Comparison of neck muscle areas
      from the present study to a previous study incorporating supine MRI demonstrated
      differing trends between anterior and posterior neck muscles that may be
      attributable to upright orientation of volunteers and planar image orientation in
      the present study. Differences between supine and upright MRI identified in the
      present study may warrant incorporation of this technique in future spinal
      imaging studies.

PMID- 20824997
TI  - Gradient compression garments as a countermeasure to post-spaceflight orthostatic
      intolerance.
AB  - INTRODUCTION: Post-spaceflight orthostatic intolerance affects approximately 30%
      of short-duration and 80% of long-duration crewmembers. While the current NASA
      antigravity suit is effective during Space Shuttle re-entry, it is not designed
      to be worn postflight and has several drawbacks. The purpose of this study was to
      evaluate the use of commercially available, thigh-high, gradient compression
      garments to prevent post-spaceflight orthostatic intolerance. METHODS: Before
      spaceflight, five male Shuttle astronauts were fitted for compression garments.
      Postflight stand time, blood pressure, heart rate, stroke volume, cardiac output,
      and peripheral resistance during 10-min, 80 degrees head-up tilt test within 4 h
      of landing in these astronauts were retrospectively compared to a group of nine
      male astronauts not wearing the compression garments. RESULTS: On landing day,
      three of nine non-countermeasure astronauts developed presyncopal symptoms and
      could not complete the test, while no countermeasure subjects became presyncopal.
      Compared to the non-countermeasure subjects, the countermeasure subjects had
      higher systolic blood pressure (116 +/- 3 vs. 134 +/- 2 mmHg), stroke volume (42
      +/- 5 vs. 57 +/- 6 ml), and cardiac output (3.1 +/- 0.3 vs. 4.6 +/- 0.4 L). Heart
      rate was not different between groups. CONCLUSIONS: In this small pilot study,
      the rate of presyncope in the non-countermeasure group was similar to that
      reported previously in subjects without a compression garment. In contrast, thigh
      high graded compression garments mitigated the symptoms of orthostatic
      intolerance by improving stroke volume, cardiac output, and systolic blood
      pressure responses to standing.

PMID- 20824998
TI  - Pulmonary barotrauma and cerebral arterial gas embolism during hyperbaric oxygen
      therapy.
AB  - Hyperbaric oxygen therapy (HBOT) is used to treat a variety of disorders. It is a
      safe treatment modality, but rare catastrophic complications may occur. In this
      case report, we describe the occurrence of irreversible spastic quadriparesis in
      a patient who suffered a cerebral arterial gas embolism (CAGE) during
      decompression from HBOT. The patient had a history of respiratory disease and was
      subsequently found to have bullous changes in the left lung, which almost
      certainly predisposed to this rare event. We discuss appropriate pretreatment
      screening to prevent such events and highlight the paradox that HBOT, the cause
      of the CAGE, is also the treatment of choice.

PMID- 20825000
TI  - Social media in aerospace medicine: the possibilities and challenges.

PMID- 20824999
TI  - Expansion of postoperative pneumothorax and pneumomediastinum: determining when
      it is safe to fly.

PMID- 20825001
TI  - You're the flight surgeon: alternobaric vertigo.

PMID- 20825002
TI  - Classics in space medicine. Comparative studies on animals and human subjects in
      the gravity-free state.

PMID- 20825003
TI  - [Characteristics of atmospheric pollutants during the period of summer and autumn
      in Shijiazhuang].
AB  - Atmospheric pollutants and their concentration change characteristics during
      Beijing Olympics in Shijiazhuang were studied. Air quality was measured by
      automatic on-line continuous monitoring equipments in summer and autumn of 2007
      and 2008. The objectives of this study were to identify the effect of pollutants
      decrease on atmospheric environment, and develop the potential influence to
      Beijing and surrounding areas. The results show that the pollutants concentration
      often exceeds state criterion except nitrogen oxides, O3 concentration in summer
      and autumn is higher, averaged hourly maximum concentration (O3-Max) is (177.2 +/
      63.0) and (105.8 +/- 61.7) microg x m(-3), the concentrations of NO and NO2 are
      (4.5 +/- 4.0), (32.7 +/- 12.4) microg x m(-3) and (21.5 +/- 16.9), (60.5 +/-
      16.9) microg x m(-3) respectively, SO2 concentration is (72.0 +/- 27.5) and (92.0
      +/- 44.4) microg x m(-3), PM2.5 and PM10 concentrations reach to (102.3 +/-
      47.6), (153.3 +/- 58.3) microg x m(-3) and (95.8 +/- 50.0), (147.4 +/- 67.0)
      microg x m(-3). Generally, pollutants declined obviously in Olympics period, the
      concentrations of NOx, O3-Max, SO2, PM2.5 and PM10 are (43.8 +/- 15.0), (142.0 +/
      54.9), (52.4 +/- 18.8), (76.7 +/- 35.1) and (116.5 +/- 38.8) microg x m(-3), and
      the reduction ratio of SO2, PM2.5 and PM10 are 34.6%, 22.8% and 21.0% compared
      with the whole monitoring period in 2008. The actuality of atmospheric pollution
      in summer and autumn was analyzed systemically, and which provided scientific
      evidences for evaluating the control measures of pollutants emission.

PMID- 20825004
TI  - [Characterization of water-soluble inorganic ions in PM2.5 and PM1.0 in summer in
      Guangzhou].
AB  - PM2.5 and PM1.0 samples were collected simultaneously during July of 2008 in
      Guangzhou. The concentrations of water-soluble inorganic ions (Na+, NH4+, K+,
      Mg2+, Ca2+, F-, Cl-, NO3-, and SO4(2-)) were determined by ion chromatography.
      Meteorological parameters, atmospheric scattering, visibility, and concentrations
      of trace gases (SO2, NO2, and O3) for this period were also recorded. The results
      showed the total water-soluble inorganic ions concentrations were (25.5 +/- 10.9)
      microg x m(-1) and (22. 7 +/- 10.5) microg x m(-3) in PM2.5 and PM1.0, which
      occupied (47.9 +/- 4.3)% and (49.3 +/- 4.3)% of PM mass respectively. Sulfate was
      the most abundant ion and contributed (25.8 +/- 4.0)% of PM2.5 mass and (27.5 +/-
      4.5)% of PM1.0 mass respectively. High temperature and high ozone level favored
      the formation of sulfate from sulfur dioxide, while the high relative humidity
      favored the formation of nitrate were observed. Moreover, sulfate, nitrate, and
      ammonium in PM2.5 and PM1.0 had great impact on the scattering coefficient and
      visibility degradation.

PMID- 20825005
TI  - [Microphysics of atmospheric aerosols during winter haze/fog events in Nanjing].
AB  - Intensive field observations of fog/haze events, including simultaneous
      measurements of aerosol particle and fog droplet size distributions, were
      conducted in Nanjing in November, 2007. Four weather conditions (fog, mist, wet
      haze and haze) were distinguished based on visibility and liquid water content
      firstly. Then, the microphysical characteristics of coarse and fine particles in
      each condition were investigated. The results showed the dominant sequence of the
      four weather conditions was haze<-->mist-->wet haze-->fog-->, wet haze-->mist<-
      >haze. The lasting time of pre-fog wet haze was longer than that of post-fog wet
      haze. The number, surface area and volume concentration of coarse particles with
      diameter larger than 2.0 micron in fog were much higher than those in the other
      three conditions, and the smallest concentrations were observed in haze. The size
      distributions of surface area and volume concentration exhibited multi-peak in
      fog droplets, while it showed single peak for coarse particles in haze, mist and
      wet haze. For the fine particles with diameter larger than 0.010 microm, the
      spectral shapes of surface area concentration are similar in fog (mist) and wet
      haze (haze) condition. The dominant size ranges of fine particle number
      concentration were in 0.04-0.13 microm and 0.02-0.14 microm for fog and wet haze,
      separately. The same dominant size ranges located in 0.02-0.06 microm for both
      mist and haze. During the transition processes from haze, mist and wet haze to
      fog, the concentration of smaller particles (less than 0.060-0.090 microm)
      reduced and vice versa for the corresponding larger particles. Temporal variation
      of aerosol number concentration correlated well with the root mean diameters
      negatively during the observation period. The number concentration of aerosol was
      the lowest and the mean diameter was the largest in fog periods.

PMID- 20825006
TI  - [Pollution characterizations and source apportionment of polycyclic aromatic
      hydrocarbons in air during domestic heating season of Xi'an].
AB  - TSP samples and gas phase air samples were collected by an improved high volume
      active air sampler during domestic heating season in Xi'an, and the
      concentrations of polycyclic aromatic hydrocarbons (PAHs) were analyzed via GC
      MS. The results showed that average concentrations of sigma 16 PAHs in TSP and
      gas phase were (108.15 +/- 41.44) ng/m3, (260.14 +/- 99.84) ng/m3, respectively.
      Two and three ring PAHs dominated in the gas phase, while more than four ring
      PAHs were mainly adsorbed on the particle phase. Good correlation was found
      between gas-particle partition coefficient and the respective sub-cooled vapor
      pressures of PAHs. A significant correlation was also found between partition
      coefficient and temperature, and the regression equation was put forward by
      stepwise linear regression method. Ratio analysis illustrated that coal burning
      and vehicle exhaust were the main source of PAHs in Xi' an. Contribution of each
      source was calculated by factor analysis and multiple linear regression. Partial
      correlation analysis was applied to study the relationship between air pollution
      indexes and some representative PAHs of individual factors, which indicated some
      PAH had same source to SO2 and NO2.

PMID- 20825007
TI  - [Concentration and change of VOCs in summer and autumn in Tangshan].
AB  - In order to study the potential impact of volatile organic compounds (VOCs) in
      summer and autumn on region ozone, ambient concentrations and changes of VOCs
      were analyzed at Tangshan from June to September 2007 and 2008, by using the
      method of two-step-concentration-gas spectrometry/mass (CCD-GC/MS). The average
      concentration in Tangshan was 163.5 x 10(-9) C. The major components were
      alkanes, aromatics, alkenes and halogen hydrocarbons which accounted for 45.9%,
      29.9%, 5.9% and 18.9% respectively. The average concentration decreased 51.9%
      compare with 2007 (340.4 x 10(-9) C), confine gas stations is the main reason of
      the decline of alkyl, the large decline is aromatic hydrocarbons, 67%, which has
      the most potential impact of ozone formation, and dichlorobenzene in industrial
      emissions has increased. The concentrations of VOCs in Tangshan were lower 8%
      than that of Beijing during the same period in 2008. The changes of VOCs during
      2008 Beijing Olympic show that in addition to traffic source industrial emissions
      is also an important source of atmospheric pollution.

PMID- 20825008
TI  - [Observational study of ozone production efficiency at the Shangdianzi regional
      background station].
AB  - Ambient O3, NOx, NOy, and CO were measured at the Shangdianzi regional background
      station from 26 March to 9 October 2008, and VOCs samples were taken and
      analyzed. This paper uses the data to obtain the ozone production efficiency
      (OPE) at Shangdianzi and studies the relationship of OPE with NO, and VOCs. In
      addition, the potential impact from the dry deposition of NOx oxidation products
      on the calculated OPE was estimated and tentatively corrected. Based on this
      study, the daily OPE varied in the range of 0.2-21.1, with an average of 4.9 +/-
      3.6. An overall OPE average of 4.3 +/- 1.5 can be obtained. The dependence of OPE
      on the NO, concentration can be described using an empirical parabolic function.
      If the concentration of NOx is lower than 14 x 10(-9), OPE increases with NO,;
      while if the concentration of NOx is higher than 14 x 10(-9), OPE decreases with
      NOx. The correlation analysis indicates that the concentrations of aromatics and
      OVOCs are positively correlated to OPE. Dry deposition of HNO3 and other NO,
      oxidation products may significantly impact the calculated OPE values, leading to
      overestimate. It is possible to correct such overestimate using the NOy/CO ratios
      obtained at an urban site and at Shangdianzi. However, this correction is less
      rigorous and the corrected OPE data remain to be validated. The uncorrected data
      can be viewed as the upper limit of the real OPE.

PMID- 20825009
TI  - [Performance of an innovative polyethylene carrier biotrickling filter treating
      hydrogen sulphide gas].
AB  - Characteristics of double-layer biotrickling filter using high density polythene
      rasching rings carrier treating waste gas containing hydrogen sulphide was
      studied. Results showed that biotrickling filter had significant advantages of
      low pressure drop and even load distribution along the reactor height. When
      removal efficiency was greater than 90%, gas retention time was 12 s, maximum
      inlet load was 110 g/(m3 x h), elimination capacity was 84 g/(m3 x h). At steady
      state, about 37%-55% of hydrogen sulfide load was removed from the lower layer.
      During long-term operation, pressure drop kept to less than 280 Pa x m(-1), the
      backwashing period was longer than two months, no biomass accumulation happened
      in the lower layer, and abnormal increase in pressure drop can be used as a
      indicator of backwashing. Reactor recovery and restart experimental results
      showed that removal efficiency recovered to 95% in 1 day after 6 days without
      H2S, pH dramatic variation of spray liquid had significant adverse impact on
      biotrickling bed reactor.

PMID- 20825010
TI  - [Temporal and spatial distribution of anthropogenic ammonia emissions in China:
      1994-2006].
AB  - Ammonia has both direct and indirect impacts on important environmental issues
      including acid deposition, regional fine particles and eutrophication. Estimation
      of anthropogenic ammonia emissions will provide valuable information for the
      pollution control of acid deposition and regional fine particle. Based on the
      provincial activity data on N-fertilizer application, livestock farming, N
      fertilizer production and populations, this paper uses emission factor method to
      estimate China's atmospheric ammonia emissions, analyzes its historical trends
      and presents its geographical distributions from year 1994 to 2006. The national
      total atmospheric ammonia emissions are estimated to be 11.06 million tons (Mt)
      in 1994, which increase quickly to 16.07 Mt in 2006. Emissions from livestock
      farming, N-fertilizer application, N-fertilizer production and human excreta have
      increased from 4.47 Mt, 5.94 Mt, 0.09 Mt, and 0.59 Mt in 1994 to 6.61 Mt, 8.68
      Mt, 0.14 Mt, 0.65 Mt respectively in 2006. Livestock farming and N-fertilizer
      application are the most important ammonia emission sources, which contributed
      40.79 and 55.53 percent of total emissions respectively in 2006. In 2006, the
      average ammonia emission intensity is 1.67 t x km(-2) but there are large
      variations among atmospheric ammonia emissions from each province. Emissions from
      provinces including Henan, Shandong, Hebei, Sichuan and Jiangsu accounted for
      40.82 percent of national emissions.

PMID- 20825011
TI  - [Comprehensive fuzzy evaluation of nitrogen oxide control technologies for coal
      fired power plants].
AB  - A multi-level assessment index system was established to quantitatively and
      comprehensively evaluate the performance of typical nitrogen oxide control
      technologies for coal-fired power plants. Comprehensive fuzzy evaluation was
      conducted to assess six NO, control technologies, including low NO, burner (LNB),
      over the fire (OFA), flue gas reburning (Reburning), selective catalyst reduction
      (SCR), selective non-catalyst reduction (SNCR) and hybrid SCR/SNCR. Case studies
      indicated that combination of SCR and LNB are the optimal choice for wall-fired
      boilers combusting anthracite coal which requires NO, removal efficiency to be
      over 70%, however, for W-flame or tangential boilers combusting bituminous and
      sub-bituminous coal which requires 30% NO, removal, LNB and reburning are better
      choices. Therefore, we recommend that in the developed and ecological frangible
      regions, large units burning anthracite or meager coal should install LNB and SCR
      and other units should install LNB and SNCR. In the regions with environmental
      capacity, units burning anthracite or meager coal shall install LNB and SNCR, and
      other units shall apply LNB to reduce NO, emissions.

PMID- 20825012
TI  - [Analysis of surface composition of three-way catalysts of in-use vehicles].
AB  - The kinds and contents of surface elements in three-way catalysts of six light
      duty in-use taxi cabs, which were mainly operated in Beijing and whose driving
      mileages were in the range of 34 x 10(4)-59 x 10(4) km, were determined by X-ray
      fluorescence spectrometry (XRF), and the effect of driving mileage on element
      content was investigated. Results showed that nearly 30 kinds of elements were
      present on the catalyst surface. The main elements of different samples were
      similar. The common elements of the pollutant on the front and rear catalysts
      were P, Ca, Zn and Mn etc., most of which are from engine oil and gasoline. S was
      only observed on the rear catalysts, indicating that S tends to deposit on the
      rear catalysts. After 34 x 10(4) km run, the P content increased very slowly and
      40 x 10(4) km run S content reached a saturated value. While the contents of Ca,
      Zn and Mn still exhibit an increase tendency after 56 x 10(4) km. That means
      after 40 x 10(4) km driving mileage, the effects of P and S on the catalyst
      activity are minor, and the continuous deposit of Ca, Zn and Mn will lead to
      further decrease of the activity.

PMID- 20825013
TI  - [Simulation research on the movement and deposition of inhalational particles in
      the human respiratory tract].
AB  - An entire 3-dimensional geometry model from mouth, pharynx, larynx, trachea to
      triple bifurcation and the mathematics models for the calculation of the fluid
      flow and inhalational particle movement in the respiratory tract were proposed in
      this paper. The deposition fraction of inhalational particles in the respiratory
      tract obtained from the numerical simulation was coincident with the experimental
      data basically. Particles were traced in the Lagrangian frame, and at the same
      time, particle deposition fraction and position were recorded based on the
      models. The movement and deposition of the inhalational particles in the upper
      respiratory tract were analyzed. The results show that the deposition of
      inhalational particles in different positions have important correlation with the
      breathing intensity, particle density and particle diameter; deposition fraction
      of the inhalational particles in the trachea will increase at high breathing
      intensity and decrease with particle diameter increased; the deposition fraction
      of the inhalational particles in the larynx is maximal and can attain 35%, but
      the influence of the breathing intensity and particle diameter on the deposition
      fraction is smaller relatively; the deposition fraction of the inhalational
      particles in the triple bifurcation will decrease observably with particle
      diameter increased; the deposition fraction of the inhalational particles in the
      triple bifurcation is higher obviously at medium and small breathing intensity
      compared with that of high breathing intensity. The simulation results of this
      paper can provide a foundation for the research of the effect of inhalational
      particles on the human health and the research of the inhaling remedy in
      medicine.

PMID- 20825014
TI  - [Surface water quality assessment in Miyun reservoir watershed, Beijing in the
      period 1980-2003].
AB  - Single factor water quality identification index was adopted to assess the
      surface water quality of Miyun reservoir watershed in Beijing using nearly 20
      years monitoring data of 4 sites, also the surface water quality pollution
      sources were analyzed. The results indicated TP had the largest temporal
      variation at every monitoring site, coefficients of variation were 93.86%,
      86.08%, 50.56% and 139.47%, respectively. The following element was Hg, the
      coefficients of its variation were 86.08%, 25.75%, 56.52% and 47.01%,
      respectively. While TN, permanganate index, BOD5, Pb and Cr were relatively
      stable with small coefficient of temporal variation. The permanganate index,
      BOD5, Pb and Cr did not exceed to the Chinese surface drinking water standard
      limit in the study period, while Hg had high pollution risk in several years,
      such as monitoring sites S1 and S3 in 1992, monitoring sites S4 in 1996. The
      major pollutants of Miyun reservoir watershed in Beijing were TN and TP, and TN
      had larger pollution risk compared with TP in most years. Comparing to that
      before the 1990s, the decade average fertilizer, pesticide and agricultural
      plastic mulch inputs after the 1990s had increased by 46%, 173% and 359%,
      respectively. The husbandry proportion in agriculture rose from 24.4% to 39.8%,
      and the average gross industrial production by 424%. The upstream of Miyun
      reservoir had larger pollution risk than its downstream. In addition, Chaohe
      watershed contributed more TN and TP to the reservoir than Baihe watershed.

PMID- 20825015
TI  - [Seasonal variation of phytoplankton community in Xiaojiang backwater area during
      the preliminary operation stage of the Three Gorges Reservoir].
AB  - According to one year's continuous observation on algae in the Xiaojiang
      backwater area in Three Gorges Reservoir, our group analyzed algae community and
      its succession in the Xiaojiang backwater area at the beginning of the function
      of the reservoir. The algae cell density and biomass are the highest in spring
      and the lowest in winter. The maximal value of cell density is 421.64 x 10(3)
      cells x L(-1), and the minimal value is 2.06 x 10(5) cells x L(-1); and maximal
      value of biomass is 39,231.84 microg x L(-1), and the minimal value is 226.17
      microg x L(-1). From May 2007 to May 2008, there are 7 phylum, 101 category, 262
      genus appeared in the Xiaojiang backwater area, in which 51 categories are
      Chlorophyta accounting for 50.5%, 22 categories are Bacillariophyta accounting
      for 21.8%, 18 categories are Cyanophyta accounting for 17.8%, and 4 categories
      are Dinophyta, 2 categories are Cryptophyta, 3 categories are Euglenophyta, 1
      category is Xanthophyta and others. Cryptomonas, Chlorella, Cyclotella,
      Scenedesmus, Oocystis, Chlamydomonas, Schroederia, Aulacoseira, Stephanodiscus
      and Fragilaria are familiar categories in the Xiaojiang backwater area.
      Asterionnella, Aulacoseira, Coelastrunm, Chlorella, Scenedesmus, Aclinastnrum,
      Dictyosphaerium, Anabaena, Aphanizomenon, Merismopedia, Ceratium, Peridinium and
      Cryptomonas are the preponderant categories in the Xiaojiang backwater area.

PMID- 20825016
TI  - [Numerical simulation for effects of hydrodynamic condition on algae growth in
      Chongqing reaches of Jialing River].
AB  - By introducing two parameters which express the optimal velocity and the velocity
      range for alga growth, a new velocity factor was put forward for the formula of
      alga growth. The 2-D unsteady ecological dynamic model for algae growth was
      established to analyze the effects of hydrodynamic condition on algae growth in
      Chongqing reaches of Jialing River. The space-time distribution of concentration
      for Chl-a was simulated numerically for various water levels under climate
      condition in the period of high frequency for water blooms in Three Gorges
      Reservoir and nutrition condition at present. The corresponding location and area
      of water blooms were forecasted. The results stated that about 0.04 m x s(-1) was
      the optimal velocity for algae growth.

PMID- 20825017
TI  - [Over-compensatory growth of Microcystis aeruginosa after high temperature
      stress].
AB  - Two groups of Microcystis aeruginosa FACHB 905 cultures, 40 degrees C and 25
      degrees c cultures were set in present study. Both of them were cultured for 5
      and 10 days before transferred to fresh medium in same cell densities and then
      cultured under the same conditions at 25 degrees C. The algae which were cultured
      under 25 degrees C for all the time were set as the control. The growth,
      chlorophyll a concentration, Fv/Fm, net photosynthetic rate and respiration rate
      were determined after re-inoculation. The result showed that the high temperature
      treated groups have lower specific growth rate and lower Fv/Fm than those of
      control groups (p < 0.01). However, in the middle-later stage of recovery growth,
      the specific growth rate of 40 degrees C for 5 days group was 0.362, and it was
      significantly higher than that of control groups of 0.301 (p < 0.05), while the
      specific growth rate of 40 degrees c for 10 days group was 0.358, and there was
      no significant difference with control. 40 degrees C for 5 days group showed over
      compensatory growth while 40 degrees C for 10 days group showed exact
      compensatory growth. It implies that the over-compensatory growth characteristics
      of Microcysis aeruginosa is an endogenous biological factor that contributing the
      outbreak of blooms.

PMID- 20825018
TI  - [Studies on nitrogen, phosphorus and organic matter in ponds around Chaohu Lake].
AB  - There are a lot of ponds around Chaohu Lake. According to location and runoff
      supply of ponds, the ponds are divided into three types: ponds inner vellage
      (PIV), ponds adjacent vellage (PAV) and ponds outer vellage (POV). The samples of
      water and sediment were collected from 136 ponds around Chaohu Lake and the
      contents of nitrogen, phosphorus and organic matter in water and sediments were
      analyzed in this study. The results showed that mean contents of total nitrogen
      (TN), NH4+ -N, NO3- -N, NO2- -N, total phosphorus (TP), soluble PO4(3-) -P and
      COD were 2.53, 0.65, 0.18, 0.02, 0.97, 0.38 and 51.58 mg x L(-1) in pond water,
      respectively; and mean contents of TN, NH4+ -N, NO3- -N, NO2- -N, TP, inorganic
      phosphorus (IP), organic phosphorus (OP) and loss of ignition (LOI) in pond
      sediment were 1575.36, 35.73, 13.30, 2.88, 933.19, 490.14, 414.75 mg x kg(-1) and
      5.44%, respectively. The ponds of more than 90% presented eutrophication in the
      contents of total nitrogen and phosphorus in water. The contents of TN and NH4+ 
      N in water and sediment of PIV were significantly higher than that of POV. And
      the contents of inorganic nitrogen in pond water and sediment displayed a
      following order: NH4+ -N > NO3- -N > NO2- -N. Data analysis indicated that there
      was a significantly positive correlation between organic matter and total
      nitrogen and phosphorus in water and sediment. The nitrogen, phosphorus and
      organic matter in ponds mainly sourced farmlands and village land surface. The
      contents of nitrogen, phosphorus and organic matter in ponds were affected by
      location and runoff supply of ponds. By retaining nitrogen, phosphorus and
      organic matter in runoff, the ponds can effectively decrease nutrient content
      into Chaohu Lake.

PMID- 20825019
TI  - [Effect of ozone/coagulation pretreatment on membrane fouling reduction].
AB  - In order to investigate the effect of ozone and coagulation pretreatments on
      organic matter and MF membrane filtration, pretreated Huangpu River surface water
      was filtrated by MF membrane. The results showed that there were the optimal
      dosages of ozone and coagulant made maximum membrane flux. The result of membrane
      fouling reduction by coagulation was better than that by ozone, which was
      relative to character of organic matter removed by two pretreatment processes.
      Organics in Huangpu River water mostly concentrates in relative molecule mass
      (Mr) ranging 3 x 10(3)-5 x 10(3). Research on the chemical cleaning of the fouled
      membrane indicated that fouling organic substance concentrated about Mr 4.5 x
      10(3). Removals of Mr 3 x 10(3) organic matter are higher than Mr 5 x 10(3)
      organic matter by ozone oxidation. Coagulation process can remove 5 x 10(3) high
      relative molecular mass organic matter effectively. Removal of these organics
      fouled membrane by coagulation was better than that by ozone, thereby to
      effectively reduce membrane fouling.

PMID- 20825020
TI  - [Preparation and characterization of zirconium hydroxide powder for fluoride
      adsorption].
AB  - The method co-precipitation was applied to preparation the zirconium hydroxide as
      a type drinking-water defluoridation adsorbent. The effect of the preparation
      conditions on the adsorptive capacity was studied. The optimization of
      preparation condition for zirconium hydroxide concludes that co-precipitation
      time is 10 h, pH value is 7.0, drying time is 72 h, calcination temperature is
      below 100 degrees C. Also, the adsorbent samples were characterized. SEM
      measurements reveal that zirconium hydroxide powder are constructed by several
      small particles, with a diameter about 20-30 microm. XRD and TG/DTA measurements
      show that the zirconium hydroxide samples have amorphous phase and converse to
      tetragonal phase when calcined at 600 degrees C. Nitrogen adsorption/desorption
      measurements show that samples have large surface areas of 138.4 m2/g and a 2 nm
      average pore size distribution in the mesopore region. The performance of
      zirconium hydroxide regeneration process was investigated. The results show that
      the regeneration techniques are very suitable to restore the fluorine-removal
      ability for zirconium hydroxide.

PMID- 20825021
TI  - [Effects of benzene, toluene on reductive dechlorination of trichloroethylene and
      its daughter product cis-1,2-dichloroethylene by granular iron].
AB  - Mixed plumes contained chlorinated solvents and petroleum hydrocarbons which
      mainly refers to BTEX (benzene, toluene, ethylbenzene and xylenes) in groundwater
      can be remediated by sequential units combined an iron permeable reactive barrier
      (Fe0-PRB) with an anoxic wall. In design of the Fe0-PRB it should be taken into
      account the necessity of altering the width of the iron cell in the presence of
      BTEX. Three column experiments were conducted to evaluate the effects of benzene,
      toluene on the long-term performance of reductive dechlorination of
      trichloroethylene (TCE) by granular iron. The results showed that the kinetics of
      TCE (at the initial concentration of 2 mg x L(-1) more or less) reduction was
      accorded with pseudo first-order even in the presence of benzene or toluene (at
      about 1-2 mg x L(-1), respectively). The existence of benzene and toluene
      inhibited the removal of TCE by 15.1% and 18. 5% , respectively; however, the
      presence of benzene slightly increased cis-1,2-DCE reduction rate by 4.5%, and
      the presence of toluene increased cis-1,2-DCE reduction rate by 42.8%. The
      inhibition of benzene and toluene other than mineral precipitates was not one of
      the decisive factors in the long-term performance of an Feo-PRB; in addition, the
      kinds of chlorinated daughter products of TCE in the presence/absence of benzene
      or toluene were identical and cis-1,2-dichloroethylene (cis-1,2-DCE), the major
      intermediate, firstly broke through from all the 3 columns at concentrations
      about 2-75 microg x L(-1), indicating that designing the width of an Fe0-PRB
      should be based on the hydraulic residence time of cis-1,2-DCE. In conclusion, if
      only considering the TCE remedial goals and disregarding the effects of cis-1,2
      DCE on BTEX biodegradation downgradient the Fe0-PRB, the results suggested that
      it should be not necessary to increase the width of the iron cell for
      constructing sequential permeable reactive barriers (SPRBs) to rescue TCE- and
      BTEX-contaminated aquifers.

PMID- 20825022
TI  - [Study on the degradation of AO7 by UV/K2S2O8, system: kinetics and pathways].
AB  - The UV photolysis of S2O8(2-) is a novel advanced oxidation technologies (AOTs),
      which leads to the formation of strong oxidizing radicals, sulfate radicals
      (SO4(*-)). The effect of oxidant K2S2O8 concentration, the initial pH of solution
      and various inorganic anions (H2PO4-, HCO3-, NO3- and Cl-) were investigated
      using AO7, a kind of azo dye, as a model pollutant. The degradation kinetics of
      AO7 followed pseudo first-order kinetics and reaction rates related to PMS
      concentrations. When the initial concentration of AO7 was 0.14 mmol/L, the
      optimal molar ratio of oxidant K2S2O8 to pollutants AO7 was 20. The effect of
      initial pH had great effect on the AO7 degradation rate during UV/K2S2O8 system.
      Increasing system pH results in the formation of *OH from SO4(*-). The effects of
      four inorganic anions (H2PO4-, HCO3-, NO3- and Cl-) all had some negative effect
      on the degradation of AO7. Based on the results of GC/MS, three main
      intermediates (2-naphthalenol, coumarin and 1,2-benzenedicarboxylic acid) were
      identified, thus the degradation pathway for SO4(*-) induced by UV/K2S2O8 was
      proposed accordingly.

PMID- 20825023
TI  - [Studies on photo-electron-chemical catalytic degradation of the malachite
      green].
AB  - A novel two-compartment photo-electro-chemical catalytic reactor was designed.
      The TiO2/Ti thin film electrode thermally formed was used as photo-anode, and
      graphite as cathode and a saturated calomel electrode (SCE) as the reference
      electrode in the reactor. The anode compartment and cathode compartment were
      connected with the ionic exchange membrane in this reactor. Effects of initial
      pH, initial concentration of malachite green and connective modes between the
      anode compartment and cathode compartment on the decolorization efficiency of
      malachite green were investigated. The degradation dynamics of malachite green
      was studied. Based on the change of UV-visible light spectrum, the degradation
      process of malachite green was discussed. The experimental results showed that,
      during the time of 120 min, the decolouring ratio of the malachite green was
      97.7% when initial concentration of malachite green is 30 mg x L(-1) and initial
      pH is 3.0. The catalytic degradation of malachite green was a pseudo-first order
      reaction. In the degradation process of malachite green the azo bond cleavage and
      the conjugated system of malachite green were attacked by hydroxyl radical.
      Simultaneity, the aromatic ring was oxidized. Finally, malachite green was
      degraded into other small molecular compounds.

PMID- 20825024
TI  - [Phase separation characteristics of an anaerobic baffled reactor treating
      organic wastewater containing sulphate].
AB  - Phase separation characteristics of anaerobic baffled reactor (ABR) treating
      organic wastewater containing sulphate were investigated in a 5-compartment ABR
      with an effective volume of 32 L. During a start-up experiments of 132 days, the
      chemical oxygen demand (COD) and sulphate (SO4(2-)) removal efficiency, volatile
      fatty acid (VFA) and sulfide (S2-) distribution in each compartment were
      measured. The microbiology communities of granular sludge were also investigated
      by scanning electronic microscope (SEM). The experimental results showed that low
      influent loading and low increase are the keys to start-up of ABR. The volumetric
      loading rates of COD and SO4(2-) increased stage and stage from 1.5 kg x (m3 x
      d)(-1) to 3.3 kg x (m3 x d)(-1) and from 0.07 kg x (m3 x d)(-1) to 0.18 kg x (m3
      x d)(-1) for 132d, and achieved a stable state that resulted in 95% COD and 85%
      SO4(2-) removal. COD had the trend of decreasing with compartments along flow
      direction, it's removal rate in compartment 1, 4 and 5 took the large proportion
      in total COD removal rate, and sulphate removal rate in the initial three
      compartments took the large proportions in the total sulphate removal rate. The
      VFA and S2- concentrations were high in the initial three compartments and
      obviously declined in the final two compartments. With the loading rate increase,
      the proportion of COD and SO4(2-) removal rates in the final room increased, the
      highest and the lowest point of VFA and S2- concentrations were gradually moved
      to hind room. The SEM observation indicated microbiology communities of granular
      sludge in each compartment were cooperative and specific, it showed that the
      acidogenic phase and methanogenic phase, sulfate-reducing phase and sulfur
      producing phase were separated in the ABR.

PMID- 20825025
TI  - [Acidification and its effect on the population distributions of microorganisms
      in an anaerobic baffled reactor].
AB  - The changes of pH, COD, volatile fatty acids (VFA) and microbial morphology of
      the acidification process in an anaerobic baffled reactor (ABR) were
      investigated. And the population succession process of the anaerobic
      microorganisms was quantitatively analyzed by using the Fluorescent In situ
      hybridization technology (FISH). The results show that the ABR reactor is
      acidified gradually from the front to the back. After the reactor is entirely
      acidified, the COD removal efficiency is only 30.9%, and the pH values are
      lowered by 1.0-2.2, while the VFA in effluent increases by 5.1 times.
      Additionally, the microbial morphology is significantly affected by the
      acidification process, in which not only the bacteria are deformed or died, but
      also the internal and external mass transfer of granular sludge becomes
      difficult. The quantitative analyses with FISH shows that in the acidification
      process the Archaea growth is inhibited but the Eubacteria growth is promoted,
      thus resulting in the sharp decrease of the three crucial microorganisms of the
      anaerobic digestion. The abundance of the butyrate-oxidizing acetogenic bacteria
      Syntrophomonas spp. reduces by 30.9%, the propionate-oxidizing acetogenic
      bacteria Syntrophobacter wolinii reduces by 85.5%, the homoacetogenic bacteria
      Acetobacterium species E. limosum reduces by 60.0%, and methanomicrobium
      Methanomicrobiales reduces by 54.3%. All these result in the upsetting of the
      mass transfer balances of different anaerobic microorganism populations.

PMID- 20825026
TI  - [Feasibility of antibiotic selective inhibition method applied for measuring
      bacterial and fungal activities distribution in activated sludge].
AB  - The study evaluated the selective inhibition method for measuring the fungal and
      bacterial distribution in the activated sludge, using glucose as sole carbon
      source, and cycloheximide and streptomycin as bactericide and fungicide,
      respectively, substrate-induced oxygen uptake rate (OUR) as bioactivity index.
      Three samples were examined, i.e., aerobic sludge in a wastewater treatment
      plant, soils and anaerobic sludge. As selective microbial biocides were applied,
      the OUR of aerobic and soils sludge reduced, whereas the OUR of anaerobic sludge
      was stimulated. When 1 mg/g cycloheximide and 2 mg/g streptomycin were applied,
      the inhibition index D of aerobic sludge was approximately 1; however, the values
      of D for soils were greater than 1 at all the dosages of bactericide or fungicide
      applied in this study. These results suggested that the antibiotics used in this
      study could selectively inhibit aerobic sludge and partially inhibit the soils.
      It was found that the selective inhibition method was suitable for aerobic sludge
      analysis, but encountered problems for the other samples, e.g., failure
      inhibition effect of antibiotic, partial inhibition and low accuracy. Further
      studies are therefore needed in the selection of antibiotic and microbial
      activity parameter.

PMID- 20825027
TI  - [Biosorption of Cd(II), Cu(II), Pb(II) and Zn(II) in aqueous solutions by
      fruiting bodies of macrofungi (Auricularia polytricha and Tremella fuciformis)].
AB  - Batch experiments were conducted to study the ability of fruiting bodies of
      Auricularia polytricha and Tremella fuciformis to adsorb Cd(II), Cu(II), Pb(II)
      and Zn(II) from aqueous solutions, including biosorption ability of the biomass
      to remove heavy metals from solutions with different concentrations, kinetics of
      adsorption, influence of co-cations, and biosorption affinity in multi
      metalsystem. Results showed that in the solutions with individual metal, the
      maximum biosorption amounts of Cd(II), Cu(II), Pb(II), Zn(II) by A. polytricha
      were 18.91, 18.69, 20.33, 12.42 mg x g(-1), respectively, and the highest removal
      rates for all cases were more than 85%. The maximum biosorption amounts of
      Cd(II), Cu(II), Pb(II), Zn(II) by T. fuciformis were 19.98, 20.15, 19.16, 16.41
      mg x g(-1), respectively, and highest removal rates for all cases were more than
      75%. In the solutions with initial concentrations of 10, 50 and 100 mg x L(-1),
      the biosorption amounts increased but the removal rates decreased as the initial
      concentrations increasing. The pseudo-second-order reaction model described
      adsorption kinetics of heavy metal ions by fruiting bodies of A. polytricha and
      T. fuciformis better than the pseudo-first-order reaction model. In the solutions
      with multi metals, the biosorption amounts of heavy metals by two biosorbent were
      in the order of Ph(II) > Cd(II) > Cu(II) > Zn(II). The ions with more negative
      charges were preferential to be sorbed. The biosorption ability of A. polytricha
      was inhibited in multi-metal solutions. In multi-metal solutions, T. fuciformis
      sorbed a higher amount of Pb(II) but lower amounts of other three ions than that
      in the individual metal solutions. The results indicated that both fruiting
      bodies of A. polytricha and T. fuciformis were potential biosorbents.

PMID- 20825028
TI  - [Comparative studies on the characteristics for Cu2+ or Zn2+ adsorption onto
      different landfilled sludge].
AB  - In this paper, it was comparatively studied about the adsorption or desorption
      behaviour for Cu2+ or Zn2+ ion onto different landfilled sludge. The results
      showed that Cu2+ or Zn2+ adsorption isotherm could significantly conform to
      Freundlich and Henry equations both for the directly landfilled sludge (SSA) and
      the solidifying landfilled sludge (SSB). Moreover, much higher adsorption
      capacities were found for Cu2+ on SSA but for Zn2+ on SSB, and the removal
      efficiency could reach 95% for Cu2+ by SSA with dosage being 10-20 g/L or Zn2+ by
      SSB with dosage being 5 g/L when the initial CU2+ or Zn2+ concentration was 128
      mg/L. However, the desorption ratio of Cu2+, Zn2+ decreased with their increasing
      adsorption amount, with the same initial concentration, it was much more
      difficult for Cu2+ to release from SSA while for Zn2+ to release from SSB.
      Relatively, first-order dynamic equation was the optimal model to describe the
      kinetics of Cu2+, Zn2+ adsorption by the two sludges, the rates for Cu2+ adsorbed
      onto SSA and for Zn2+ adsorbed onto SSB were much higher at the same adsorption
      time. FTIR analysis showed that, the site for Cu2+ adsorption onto SSA is the Si
      O group from silicate and carboxy groups from aromatic acids or fatty acids which
      making stable complex compound with CU2+, while it was specific adsorption by Me-
      O group from metal oxide and hydroxyl group or carboxy groups from fatty acids
      for Zn2+ adsorption onto SSB.

PMID- 20825029
TI  - [Effect of solid content on thermal hydrolysis characteristics and flowability of
      high solid content sewage sludge].
AB  - Thermal hydrolysis characteristics of high solid content (7%, 9% and 13%) sludge
      were studied by thermal hydrolysis test. Anaerobic biodegradation of treated and
      untreated sludge and the relation of sludge flowability and sludge solid content
      were tested by biochemical methane potential (BMP) procedure and theological
      test, respectively. Results show that the dissolving ratio of solid organics
      increase with the prolonging of thermal hydrolysis time, and solid organics
      dissolve slowly after 30 min. Solid organics dissolving ratio of sludge with 7%
      solid content is higher than that of 9% and 13% sludge. The dissolving ratio of
      suspended solid (SS), volatile suspended solid (VSS) and COD of sludge with 7%
      solid content at 170 degrees C with 30 min were 43%, 47%, 42% respectively, and
      VFA/SCOD is 20.2%. Anaerobic biodegradation of treated sludge is improved.
      Methane production of 7%, 9% and 13% sludge at 170 degrees C with 30 min were
      44%, 27% and 9% higher than that of untreated sludge. Methane production ratios
      increased 63%, 74% and 37% respectively. Methane content and methane production
      ratio of 9% sludge is higher than that of 7% and 13% sludge. Yield stress
      increases slowly with the increasing of solid content when solid content is lower
      than 9%, and it increases much faster and leads a steep decrease of sewage sludge
      flowability as solid content is higher than 9%.

PMID- 20825030
TI  - [Monitoring the stoichiometric relation of ammonium oxidation with the titrimetry
      of hydrogen ion variation].
AB  - A set of automatically titrimetric system to monitor the hydrogen ion variation
      during biological wastewater treatment process in a batch bioreactor was
      developed, which consists of a batch bioreactor, data auto-acquisition and
      preservation unit, and titrant autodosing unit. The accuracy of measurement for
      the system was evaluated by measuring the stoichiometric ratio of hydrogen ion
      production amount to ammonium consumption amount of ammonium oxidation in an
      activated sludge system. The ratios measured in a 1L bioreactor with NH4+ -N
      concentrations of 1.67, 3.33, 8.33, 16. 66 and 30.00 mg/L as N respectively were
      very close to the theoretical value, and the relative errors were among 2.09%
      6.34%. However, the relative errors in bioreactors of 1, 2, 3 and 4 L with NH4+ 
      N concentration of 16.66 mg/L as N were among 2.09%- -18.57%, and increased
      significantly with accretion of the volume of bioreactor. The buffers of
      bicarbonate and the ammonium, especially the titrimetric dynamic effects in a
      larger bioreactor are the primarily factors resulting in errors. This study
      provides an important approach for monitoring hydrogen ion variation in the
      process of biological wastewater treatment by titrimetry.

PMID- 20825031
TI  - [Development of a low-cost single chamber microbial fuel cell type BOD sensor].
AB  - The principle of the detector is based on the effect of microbial toxicity of
      water sample on the electricity generation in microbial fuel cell (MFC). The
      performance of the MFC-type biotoxicity detector was evaluated with the synthetic
      water containing heavy metals of Cd2+ and Cu2+. The experimental results
      demonstrated that: (1) relative to the conventional methods, the MFC-type
      detector is easy to operate, and suitable for on-line measurements with high
      sensitivity; (2) it only requires 4 h to complete measurements, and can get ready
      for next measurement within 4 h; (3) there is a significant linear correlation
      between the concentration of toxic metal(s) and inhibition ratios in Coulombic
      yields of MFC. As the IC20 (concentration causing 20% inhibition) of Cd2+, Cu2+
      and mixed metals (Cd2+ and Cu2+) were 0.6, 0.8 and 0.25 mg/L, the regression
      coefficients were shown to be 0.9960, 0.9744 and 0.9907.

PMID- 20825032
TI  - [Simultaneous electricity generation and nitrification in a microbial fuel cell
      with aerobic biocathode].
AB  - The present study demonstrated simultaneous electricity generation and
      nitrification in a two-chamber microbial fuel cell (MFC) with aerobic biocathode
      seeded with nitrifying bacteria. Nitrification process and power production
      simultaneously happening in the same region not only saved energy consumption of
      aeration by making the best use of oxygen, but also produced additional proton by
      nitrification process, which effectively prevented alkaline at the cathode caused
      by power production. The maximum nominal current and maximum power density were
      47 mA and 45.50 W/m3, respectively. The NH4+ -N removal rate was 5.98 mg/(L x d)
      when NH4+ -N concentration was 153.4 mg/L. The nitrifying bacteria competed with
      electrochemically-active bacteria for oxygen. However, the nitrification was of
      little effect on bioelectricity production when oxygen concentration was as high
      as 3.5-5.0 mg/L. The average cathodic voltage with addition of NH4+ -N was 124 mV
      higher than that of without NH4+ -N addition when no buffer was added in the
      medium. Cathodic variations were corresponded with nitrification process. The
      theoretical calculation of H+ ion proved that, the additional H+ ion produced by
      nitrification process (8.14 x 10(3) mol) was similar with the H+ ion consumed by
      power production process (8.54 x 10(-3) mol), which confirmed that nitrification
      could compensate the pH gradient caused by bioelectricity process in the cathode,
      and maintained the stable pH value to a certain extent.

PMID- 20825033
TI  - [Researches on the estimate methods and applications of soil environmental
      geochemical baseline at a regional scale].
AB  - Regional soil environmental geochemical baseline is a base tool for studying
      material changes in the earth surface system at a regional scale as well as for
      the assessment of natural and human activities impacts on the changes of chemical
      elemental contents in the soil environment. We choose the Yangtze River Delta
      (YRD) region and Pearl River Delta (PRD) region as cases to estimate the regional
      soil environmental geochemical baseline of ten trace elements including As, Cd,
      Co, Cr, Cu, Hg, Ni, Pb, Zn, Se. Two methods including cumulative distribution
      frequency (CDF) and average estimation based on weighted soil area were applied
      to estimate the baseline of different soil categories at a regional scale and the
      whole region, respectively. A consistent result was obtained based on the two
      methods, implying the feasibility of the methods for baseline estimation. The
      estimated baselines were further used to assess the impacts on accumulation and
      contamination of trace elements caused by geochemical enrichment and human
      activities in YRD and PRD regions. For the instance of PRD region, Cd level has
      increased from 0. 035 mg/kg to 0.13-0.22 mg/kg and Hg level has increased from
      0.045 mg/kg to 0.15 mg/kg by compared the baselines to soil environmental
      background levels investigated 20 years ago. Such a change implies a typical
      trend of heavy metal contamination in soil at a regional scale.

PMID- 20825034
TI  - [Vertical transporting risk of nitrogen in purple soil affected by surfactant].
AB  - The simulated leaching experiment was conducted to determine the effects of
      surfactant of sodium dodecyl benzene sulphonate (SDBS) on vertical transporting
      of nitrogen in purple soil. SDBS could reduce NH4+ -N loss from soil, and the
      higher concentration of SDBS, the less loss. SDBS could increase NO3- -N loss
      from soil, and the order of accumulation loss is SDBS100 > SDBS40 > SDBS0 >
      SDBS5. Lower concentration SDBS decrease TKN loss, but higher concentration SDBS
      had a reverse effect, and compared with SDBS0, the accumulation loss TKN of
      SDBS40, SDBS100 increased by 16.8%, 22.36%, respectively. SDBS could affect
      vertical transporting of nitrogen in purple soil, that is, the significant down
      transporting of nitrogen was observed after leaching with SDBS, and the higher
      concentration of SDBS, the more obviously transporting trend.

PMID- 20825035
TI  - [Nitrate nitrogen leaching and residue of humic acid fertilizer in field soil].
AB  - To elucidate the potential influence of humic acidfertilizer on groundwater and
      soil quality in clay soil (CS) and sandy soil (SS), nitrate nitrogen leaching and
      residue of different fertilizers in field soil were studied using a self-made
      leaching field device. Nitrate nitrogen concentration in leaching water of
      fertilizer treatments was 28.1%-222.2% higher than that of non-nitrogen treatment
      in different times, but humic acid fertilizer could prevent nitrate nitrogen
      leaching both in CS and SS, especially in CS. Nitrate nitrogen concentration of
      leaching water in CS was 41.2%-59.1% less than that in SS and the inhibiting
      effect in CS was greater than that in SS. Nitrate nitrogen could be accumulated
      in soil profile by fertilizer application. The residue of nitrate nitrogen
      retained in 0-40 cm soil layer of humic acid fertilizer treatment was 59.8% and
      54.4% respectively, higher than that of urea and compound fertilizer treatments.
      Nitrate nitrogen amount of humic acid, urea and compound fertilizer treatments in
      SS was significantly less than that in CS, being 81.7%, 81.1% and 47.6%
      respectively. Compared with the conventional fertilizer, humic acid fertilizer
      treatment improved the contents of organic matter, available nitrogen,
      phosphorus, and potassium of upper layer soil as well as cation exchange
      capacity. Besides, total amount of water-soluble salts in humic acid fertilizer
      treatment was decreased by 24.8% and 22.5% in comparison to urea and compound
      fertilizer treatments in CS, respectively. In summary, the application of humic
      acid fertilizer could improve physical and chemical properties of upper layer
      soil and reduce the risk of potential pollution to groundwater.

PMID- 20825036
TI  - [Dynamics of polycyclic aromatic hydrocarbons (PAHs) in the paddy-soil system
      during the crop rotation process].
AB  - The concentrations of polycyclic aromatic hydrocarbons (PAHs) in the paddy root
      soil system were determined to study the dynamic and the influencing factors
      during crop rotation period. It showed that the dynamic of PAHs in paddy roots
      was most correlative with the factor of root surface area, but less correlated
      with PAHs in air and particles, which indicates that the physiological characters
      rather than the environment media are the main factors influencing the PAHs
      accumulation in paddy roots. According to the EPA risk standard about BaP and
      sigma PAHs, the PAHs accumulation in the paddy seeds won't decrease the food
      security to human being. The PAHs concentrations in paddy soil showed a declined
      trend during the period of paddy growth, which was affected not only by the
      processes of water elution and microbe degradation, but also depended on the
      absorption rate of paddy roots. When the crop rotation begins and paddy planting
      rolls into the next growing period, the PAHs in the paddy soil will again
      increase into a higher level which is correlated with the TOC content in the
      soil.

PMID- 20825037
TI  - [Flushing of phenanthrene in sandy soils by triton X-100 and sodium dodecyl
      sulfate].
AB  - A comparison of column flushing for phenanthrene-contaminated sandy soils was
      made by using an anionic surfactant, sodium dodecyl sulfate (SDS), a nonionic
      surfactant, Triton X-100 (TX100), and their mixed surfactants (SDS-TX100). The
      tested concentrations of surfactants were 1000, 1750, 2500 and 3250 mg x L(-1)
      while the mass ratios of SDS to TX100 (S:T) in the mixed surfactants were 1:1,
      1:2 and 1:4. It was shown that the elution curves (phenanthrene concentration in
      elutant versus porous volume number) by SDS were zigzag fluctuating rather than
      regular patterns while those by TX100 and SDS-TX100 were regular ones in which
      the phenanthrene concentrations in elutant increased, achieved maximum and then
      decreased with the porous volume numbers of eluting solutions. Moreover, the
      maximum phenanthrene concentrations increased and the total porous volume numbers
      decreased with surfactant concentration increasing. Given the surfactant and
      total porous volume number, the removal efficiencies of phenanthrene were
      positively related to surfactant concentrations. The removal efficiencies by
      TX100 and SDS-TX100 depended on concentration and ratio of surfactant and were
      much larger than those by SDS. Given 1000, 1750 and 2500 mg x L(-1) of the
      surfactant concentrations respectively, the removal efficiencies by TXl00 and SDS
      TX100 were more than 95% but the total porous volume numbers by SDS-TX100 were
      less than those by TX100. Given 3250 mg x L(-1) of the surfactant concentration,
      the total removal efficiencies by five surfactants (i.e., SDS, TX100, S:T = 1:1,
      S:T = 1:2 and S:T = 1:4) achieved their maximum values as 70.8%, 99.9%, 99.9%,
      98.7% and 99.2%, respectively, but the needed porous volume numbers by TX100 were
      the least among those by all surfactants. The results illustrates that the
      factors such as type, concentration and ratio of surfactant play important roles
      in surfactant-enhanced flushing remediation for soils contaminated by organics.

PMID- 20825038
TI  - [Influence of enhanced UV-B radiation and straw application on soil respiration
      in soybean field].
AB  - Field experiment was carried out in 2008 in order to investigate the effects of
      enhanced UV-B radiation and straw application on soil respiration in soybean
      field. LI-8100 automated soil CO2 flux system was used to measure soil
      respiration under 20% enhanced UV-B radiation, straw application, 20% enhanced UV
      B radiation + straw application and control. Environmental factors such as air
      temperature, soil temperature and moisture were also measured. Results indicated
      that supplemental UV-B radiation reduced soil respiration rate by 30.31%, straw
      application increased soil respiration rate by 14.51%, while enhanced UV-B
      radiation + straw application combined treatment had no significant effect on
      soil respiration. Enhanced UV-B radiation enhanced the carbon conversion rate of
      straw. Significant relationship were found between soil respiration rate and soil
      temperature under the control, enhanced UV-B, straw application, and enhanced UV
      B + straw application, the fitting equation determined coefficients R2 were
      0.434, 0.563, 0.451 and 0.513. The Q10 (temperature sensitivity coefficients) for
      soil respiration were 1.55, 1.91, 1.80 and 1.71, respectively. It was reflected
      that enhanced UV-B radiation, straw application and enhanced UV-B radiation +
      straw returning increased the Q10 for soil respiration.

PMID- 20825039
TI  - [Effects of ozone stress upon winter wheat photosynthesis, lipid peroxidation and
      antioxidant systems].
AB  - Stress effects of surface increased ozone concentration on winter wheat
      photosynthesis, lipid peroxidation and antioxidant systems in varied growth
      stages (jointing stage, booting stage, blooming stage and grain filling stage)
      were studied, the winter wheat was exposed to open top chambers (OTCs) in an open
      field conditions to three levels ozone concentrations (CK, 100 nmol x mol(-1),
      150 nmol x mol(-1)). The results revealed that within 150 nmol x mol(-1) ozone
      concentration, as the ozone concentration and time increased,total chlorophyll
      content,chlorophyll a and b contents of winter wheat leaves were general
      declined,but compared to CK, the total chlorophyll and chlorophyll a content of
      T1 treatment groups were a little higher at booting and blooming stage; the
      conductance of stomatal was affected, the activation of unit leaf area decreased,
      intercellular CO2 concentration and stomatal limitation value showed a
      fluctuation change tendency. At the same time, a self-protective mechanism of
      winter wheat were launched. Concrete expression of SOD activity first increased
      rapidly and then gradually decreased, the activity of POD showed a decrease
      firstly and then rapidly increased. From the jointing stage to the blooming stage
      and from the grain filling stage one to grain filling stage two, the activity of
      CAT rapidly increased first and then comparatively decreased, but the content of
      MDA kept steadily rising. The carotenoid content increased first and then
      decreased, heat dissipation of unit leaf area increased. These results indicate
      that antioxidant enzymes can not completely eliminate excessive reactive oxygen
      species in vivo of winter wheat, then lead to accumulation of reactive oxygen
      species, further exacerbate the lipid peroxidation, that result in the increase
      of membrane permeability, degradation of chlorophyll, reduction of net
      photosynthetic rate, imposing on the winter wheat leaves senescence process.

PMID- 20825040
TI  - [Combined injured effects of acid rain and lanthanum on growth of soybean
      seedling].
AB  - Combined effects of acid rain and lanthanum on growth of soybean seedling
      (Glycine max) and its inherent mechanism were studied in this paper. Compared
      with treatments by simulated acid rain (pH 3.0, 3.5, 4.5) or rare earth La(III)
      (60, 100 and 300 mg x L(-1)), the decrease degree of growth parameters in
      combined treatments was higher, indicating that there were a synergistic effects
      between acid rain and La. Moreover,the inhibition effects of acid rain and
      La(III) were more obvious when pH value of acid rain was lower or the
      concentration of La(III) was higher. The changes of photosynthetic parameters
      were similar to those of growth, but the decrease degree of each parameter was
      not same in the same treatment group. The decrease degree of optimal PSII
      photochemical efficiency (Fv/Fm) and chlorophyll content (Chl) were 9.35%-22.75%
      and 9.14%-24.53%, respectively, lower than that of photosynthetic rate Pn (22.78%
      84.7%), Hill reaction rate (15.52%-73.38%) and Mg2+ -ATPase activity (14.51%
      71.54%), showing that the sensitivity of photosynthetic parameters to the
      combined factors was different. Furthermore, relative analysis showed that the
      change of Pn were mainly affected by Hill reaction rate and Mg2+ -ATPase
      activity, and was less influenced by Chl and Fv/Fm. It indicates that the effect
      of acid rain and La on each reaction in photosynthesis was different, and the
      inhibition of combined treatments on photosynthesis in plants was one of the main
      factors affecting growth of plant.

PMID- 20825041
TI  - [Effect of different zinc levels on accumulation and chemical forms of cadmium,
      and physiological characterization in Capsicum annuum L].
AB  - Pot experiments were carried out to investigate the influence of different zinc
      (Zn) levels (0, 100, 200, 400 and 600 micromol x L(-1)) on the plant
      growth,activities of antioxidant enzymes, contents of chlorophyll a and b,
      accumulation and chemical forms of cadmium (Cd) in Capsicum annuum L. when
      exposed to Cd (20 mg x kg(-1)). The results showed that dry weights of leaf,
      stem, fruit and root, and contents of chlorophyll a and b in Capsicum annuum L.
      were increased by Zn ( < or = 400 micromol x L(-1)), while inhibited by high Zn
      (600 micromol x L(-1)). Activities of superoxide dismutase (SOD) and catalase
      (CAT) were reduced by Zn ( < or =400 micromol x L(-1)), the lowest activities of
      SOD and CAT were recorded in 400 micromol x L(-1) Zn, but activities of SOD and
      CAT were increased when Zn >400 micromol x L(-1). Cadmium concentrations in stem,
      fruit and root of Capsicum annuum L. were decreased by 2.7%-5.4%, 7.5%-28.1% and
      7.6%-21.8% in the presence of Zn when exposed to Cd. The total extractable Cd,
      NaCl- extractable Cd, water-extractable Cd and ethanol-extractable Cd in fruit
      were reduced by 7.7%-21.8%, 4.11%-23.6%, 54.5%-66.8% and 4.8%-86.7% in the
      presence of Zn,while acetic acid- extractable Cd and residual Cd were increased
      by 28.0%-68.0% and 12.6%-25.0%.

PMID- 20825042
TI  - [Rapid biochemical method for the detection of paralytical shellfish poisoning
      toxins in shellfish from seafood market].
AB  - A rapid biochemical method was discussed in order to detect low concentration of
      paralytic shellfish poisoning (PSP) in sea food. The mice were injected with PSP
      extract of bivalves (1 and 0.2 microg/kg respectively, as STX equivalents)
      purchased from seafood market. ACh, AChE, NO and NOS in blood were studied at 15,
      60, 120 min respectively. The results showed that at low dose (0.2 microg/kg) and
      15 min, only the contents of ACh changed significantly compared with control
      group (p < 0.05), which was (141.2 +/- 14.8) microg/mg, while the contents of NO
      and the activities of NOS changed until 120 min, compared to control group (p <
      0.05) ,which were (68.7 +/- 3.8) micromol/g and (40.1 +/- 4.9) U/mg respectively.
      At high dose the contents of ACh changed at all three time point. It can be
      suggested that the contents of ACh is the only one of four indexes which can
      response to PSP at low dose in an early stage (15 min) and may be selected as a
      biochemical index for rapid detection of PSP.

PMID- 20825043
TI  - [Identification and phylogenetic analysis of an isolated denitrifier from
      rotating drum biofilter].
AB  - A heterotrophic denitrifying strain named ND1 has been isolated from rotating
      drum biofilter (RDB) which was mainly used for the treatment of exhaust gas such
      as NOx. It was proved to be Gram-negative. In addition, it was able to form dry
      and wrinkled colonies on the medium, adhere on the agar surface, produce yellow
      pigments and be motile with a single polar flagellum. It was indentified as the
      Pseudomonas stutzeri according to morphological and physiological biochemical
      characteristics and 16S rDNA sequence analysis. Under the conditions of pH 7.2
      and temperature 30 degrees C, the NO3- -N removal efficiency by ND1 was up to
      100% in 5 days,while the NO2- -N degradation ratio was only 85% by the strain DN1
      when subjected to the same condition as the above.

PMID- 20825044
TI  - [Biodegradation characteristics of o-chlorophenol with photosynthetic bacteria
      PSB-1D].
AB  - A strain of photosynthetic bacteria named PSB-1D with degradation of o
      chlorophenol (2-CP) was isolated and screened from the shallow substrate sludge
      in downstream side of the sewage outfall of an insecticide factory. The PSB-1D is
      identified preliminarily as Rhodopseudomonas sp. according to its colony and cell
      morphological properties, physiological biochemical characteristics and
      absorption spectrum analysis of living cells. The experiments results of
      relationship between PSB-1D growth and o-chlorophenol degradation showed that the
      degradation rate of o-chlorophenol was up to 57.26% after 7 days cultural time.
      The main environmental factors including way of illumination and oxygen, initial
      pH, cultural temperature, illumination intensity had distinctly influenced on the
      o-chlorophenol degradation with PSB-1D. The results showed that the optimum
      conditions were as following: an anaerobic light, pH 7.0, temperature 30 degrees
      C, illumination intensity 4000 lx,initial o-chlorophenol concentration 50 mg/L.
      Under that cultural condition, the degradation rate of o-chlorophenol could reach
      to 62.08%. The degradation kinetic data fitted the Andrews model well. In
      addition, the biodegradation process of o-chlorophenol can be well described by
      enzymatic reaction of high concentration inhibition, with the maximum substrate
      utilization rate 0.309 d(-1), Michaelis-Menten constant 2.733 mg/L, inhibitory
      constant 230.15 mg/L respectively.

PMID- 20825045
TI  - [Study on the function of plasmid in pyridine-degrading bacteria].
AB  - In order to identify the characteristics of the plasmids of degrading bacterial
      strains and the relationship between the plasmids' function and biodegradation,
      plasmids were isolated from two bacterial strains (Paracoccus sp. BW001 and
      Shinella zoogloeoides BC026) and pulse-field gel electrophoresis was used to
      identify the distribution of plasmids and their molecular size. Two large
      plasmids with 190-245 kb and one small plasmid with 4.5-5.0 kb were found in the
      BW001, and at least 3 large plasmids over 200 kb were harbored in the BC026. The
      plasmid curing was conducted by high temperature-SDS method and the results
      indicated the biodegradation genes might locate in the plasmids of two bacterial
      strains. After transforming the plasmids of BW001 into E. coli 5alpha by
      electroporation, the new bacterial strain could tolerate pyridine.

PMID- 20825046
TI  - [Effect of surfactant on the evaporation of p-chloronitrobenzene and naphthalene
      in the turbulent process].
AB  - Effect of surfactant on the evaporation of p-chloronitrobenzene and naphthalene
      in the turbulent process was studied in order to understand the effect of
      surfactant on the evaporation of complex contaminants in dynamic water system.
      Sodium dodecyl sulfate (SDS), cetyltrimethyl ammonium bromide (CTMAB) and
      polyethylene glycol sorbitan monolaurate (Tween 20) were used in the experiment.
      The results showed that the evaporation of p-chloronitrobenzene and naphthalene
      from surfactant solution in set turbulence intensity followed the first kinetic
      equation and all the correlation coefficients were above 0.99. The evaporative
      loss velocity of component was increased in dynamic water,while it decreased in
      surfactant solution, comparing with static pure water. The combined impact of
      these two factors was mainly presented promoting. When the turbulence intensity
      was above 39 r/min and 65 r/min respectively and the concentrations of
      surfactants were set from 150 mg/L to 2000 mg/L, the corresponding evaporative
      loss velocity of naphthalene and p-chloronitrobenzene both increased clearly. The
      evaporative loss velocity of p-chloronitrobenzene and naphthalene in the same
      turbulence intensity were decreased because of the straining ability of
      surfactant with the rule: CTMAB > Tween 20 > SDS. The impact of both surfactant
      and turbulence on naphthalene (with higher H) was more distinct than p
      chloronitrobenzene (with lower H).

PMID- 20825048
TI  - [Innovative ET cover system and its hydrologic evaluation].
AB  - The evapotranspiration (ET) cover system,as an alternative cover system of
      landfill, has been used in many remediation projects since 2003. It is an
      inexpensive, practical,and easily maintained biological system, but is mainly
      favorable in arid and semiarid sites due to limited water-holding capacity of the
      single loam layer and limited transpiration of grass. To improve the
      effectiveness of percolation control, an innovative scheme of ET was suggested in
      this paper: (1) a clay liner was added under the single loam layer to increase
      the water-holding capacity; (2) combined vegetation consisting of shrub and grass
      was used to replace the grass cover. Hydrologic evaluation of conventional
      cover,ET cover and the innovative ET cover under the same condition was performed
      using the computer program HELP, which showed the performance of the innovative
      ET cover is obviously superior to that of ET cover and conventional cover.

PMID- 20825047
TI  - [Optimization on slow-release inhibition of biomethane and the kinetics model of
      diffusion].
AB  - The diffusion mechanism of acetylene,which can inhibit the activity of
      methanogens, was studied. Paraffin wax and rosin were used as matrix of slow
      release and calcium carbide was used as inhibition material. Based on the T.
      Higuchi equation and the characteristics of slow-release inhibitors, a mechanism
      model was derived. Moreover, the effective diffusion coefficients (De) can be
      acquired by this model. During the diffusion process, the reaction heat of
      calcium carbide and water could make acetylene gas expansion and caused the slow
      release inhibitors expansion if the hardness of the slow-release inhibitors is
      inadequate. The hardness and compactness were enhanced and the effective
      diffusion coefficients reached 2.2849 x 10(-8) cm2/min (R2 = 0.9901) when the
      mass faction of rosin was 20% and the mass ratio of matrix to calcium carbide was
      1/1. Hence,the mitigation the methane generation with municipal solid waste (MSW)
      can be achieved by the technology of slow-release inhibition.

PMID- 20825049
TI  - [Collagen type III biosynthesis by cultured pubocervical fascia fibroblasts
      surrounding mono and multifilament polypropylene mesh after estrogens and
      tamoxifen treatment].
AB  - AIM: Surgical procedures using synthetic implants are currently considered as the
      most efficient therapy for stress urinary incontinence (SUI) and pelvic organ
      prolapse (POP). Insertion of the tape or mesh causes enhanced collagen synthesis
      that largely affects the biomechanical property of the implant. This process is
      significantly modulated by estrogens and improper wound healing and treatment
      failure may result in hypoestrogenism. The aim of the study was to assess the
      rate of collagen type II synthesis by pubocervical fascia fibroblasts cultured
      with polypropylene meshes in the presence of estrogens and tamoxifen. MATERIAL
      AND METHODS: Fibroblasts were obtained from pubo-cervical fascia sampled from a
      52-year-old premenopausal woman who underwent surgical treatment for SUI and
      cultured with monofilament or multifilament polypropylene meshes in the presence
      of 17B-estradiol, estriol, daidzein or tamoxifen. The cultures were run for 216
      hr and the media were replaced every 72hr N-terminal propeptide of type III
      procollagen (PIIINP) was used as a marker of collagen type III synthesis. Its
      concentration in the media was measured by radioimmunoassay Pubocervical fascia
      fibroblast cultured with monofilament or multifilament meshes are capable of
      collagen type III synthesis. Following treatment with estradiol or tamoxifen, the
      highest PIIINP concentrations were observed after 72 hr whereas in case of
      estriol, daidzein or no treatment after 144hr of culture, regardless of the type
      of mesh used. RESULTS: Only in cultures containing monofilament mesh and
      stimulated with estriol the high rate of collagen type III synthesis persisted
      until the end of the experiment. Paradoxically the highest total production of
      PIIINP was observed in culture treated with tamoxifen, both for multifilament and
      monofilament meshes. CONCLUSION: The rate of collagen type III synthesis by
      pubocervical fascia fibroblast cultured with polypropylene meshes is subjected to
      modulation by estrogens and antiestrogens.

PMID- 20825050
TI  - Prospective clinical study of the association between plasma level of free IGF-1
      and myometrial invasion min patients with endometrial adenocarcinoma.
AB  - INTRODUCTION: Endometrial carcinoma is a common malignancy of the female genital
      tract. There is a strong correlation between myometrial invasion and clinical
      prognosis. Increasing myometrial penetration is associated with an increasing
      risk of pelvic and para-aortic lymph node metastasis, adnexal metastasis,
      positive peritoneal cytology local vault recurrence, and hematogenous spread. The
      causal role for Insulin-like growth factor-1 and insulin in endometrial
      carcinogenesis is well supported and insulin and IGF system have mitogenic and
      antiapoptotic activity Endometrial cancer cell lines express high-affinity
      insulin receptors, consistent with there being a direct biological effect of
      insulin and IGF system on the growth and myometrial invasion of endometrial
      cancer cells. MATERIAL AND METHODS: Patients with endometrial carcinoma have been
      divided into three groups: tumor confined to the endometrium (stage IA, n:24),
      endometrial carcinoma with a minimal invasion (less than 50% of the myometrium;
      stage IB, n:32), and the control group (n:40). Demographic factors, estradiol and
      free IGF-1 plasma levels have been compared in all groups. RESULTS: Lower Free
      IGF-1 plasma levels were found in patients with myometrial invasion when compared
      to the patients without myomnetrial invasion. CONCLUSIONS: In the following work
      we have presented the current understanding of endometrial carcinoma, association
      between free IGF-1 plasma levels and myometrial invasion in patients with
      endometrial adenocarcinoma in terms of management and survival.

PMID- 20825051
TI  - [No association between MTHFR 677C>T polymorphism and ovarian cancer risk in
      BRCA1 mutation carriers in Wielkopolska region].
AB  - BACKGROUND: Increasing evidence indicates that genetic factors are involved in
      the process of carcinogenesis. BRCA 1 mutation has been proven to be responsible
      for increased risk of ovarian cancer However the importance of other genetic
      disorders, such as MTHFR polymorphism for increased risk of carcinogenesis, is
      still to be determined. Abnormal methylation seems to play a significant role in
      ovarian cancer pathogenesis. MTHFR catalyses the conversion of 5,10
      methylenetetrahydrofolate into 5-methyltetrahydrofolate which is a co-substrate
      in homocysteine remethylation into methionine. Thermolabile MTHFR protein
      variants with lower enzymatic activity are the effects of the mutation. AIM: The
      evaluation of 677C>T MTHFR polymorphism frequency in the group of ovarian cancer
      women with BRCA 1 mutation. The assessment of the MTHFR 677C>T polymorphism
      influence on ovarian cancer risk. METHODS: A group of 153 patients with ovarian
      cancer (Caucasian, Polish population in Wielkopolska region) were included into
      the study 3 mutations: 5382insC, C61G and 4153delA in BRCA1 gene, and genotype
      frequency within 677C>T MTHFR polymorphism, were identified. The analysis of
      genotype frequency was performed by means of PCR/RFLP method. RESULTS: 127 women
      without BRCA1 mutation and 26 with one of the mutations: 5382insC, C61G or
      4153delA were qualified for the investigation. In the group with BRCA 1 mutation,
      3 out of 26 patients were with TT genotype mutation of 677C>T polymorphism (12%).
      Heterozygotic genotype CT appeared in 13 cases out of 26 (50%), homozygotic CC in
      10 out of 26 (38%). In the group of 127 ovarian cancer patients without BRCA1
      mutation, TT genotype in 677C>T polymorphism was present in 5 women (4%).
      Heterozygotic genotype CT appeared in 61 cases (48%), similarly to homozygotic
      genotype CC-61 (48%). The highest value (OR = 3.18) was obtained when comparing
      the homozygotic TT genotype groups. None of the obtained values was statistically
      significant. CONCLUSION: Contrary to numerous suggestions in various
      publications, we did not confirm the correlation between MTHFR 677C>T
      polymorphism and the influence on the risk of ovarian cancer in BRCA1 mutation
      carriers in the investigated group of Polish women.

PMID- 20825052
TI  - [Predictive value of CA 125 in detection of ovarian cancer in pre- and
      postmenopausal patients].
AB  - AIM: The aim of the study was to evaluate the usefulness of CA125 measurements in
      ovarian cancer diagnostics in pre- versus postmenopausal women. MATERIAL AND
      METHODS: The study group consisted of 99 serum specimens of women diagnosed with
      ovarian cancer (28 pre- and 71 postmenopausal). The control group consisted of 86
      specimens collected from women without any ovarian pathology (34 pre- and 52
      postmenopausal). CA 125 measurements were performed with Zymed Laboratories CA
      125 ELISA Kit. Descriptive statistics, including mean values, standard deviation
      (SD) and 95CI of CA 125 among pre- and postmenopausal women, were calculated. The
      usefulness of CA 125 measurements in ovarian cancer diagnostics was assessed by
      calculating specificity sensitivity positive and negative predictive rates among
      pre- versus postmenopausal women. Statistical calculation was preformed with the
      use of STATISTICA 6.0 StatSoft Inc. (2001) software (wwwstatsoft. com). RESULTS:
      Higher CA 125 concentrations were observed in controls among pre- versus
      postmenopausal women (10.01 +/- 15.41; 95% CI: 4.63-15.39 IU/ml vs. 8.88 +/-
      13.74; 95% CI: 5.06-12.71/U/ml, respectively NS). In contrary among women with
      ovarian cancer CA 125 levels were higher in postmenopausal women when compared to
      premenopausal (352.11 +/- 432.07; 95% CI: 184.57-519.65 vs. 541.59 +/- 547.98 95%
      CI: 411.89-671.29, respectively p < 0.05). In premenopausal group the CA 125
      sensitivity was calculated at 64% whereas specificity 94.12% (FPR 5.9%; OR:
      10.9), positive predictive value 90% and negative predictive value 94.12%. Among
      postmenopausal women results were as follows: sensitivity 88.73%, specificity
      98.07% (FPR 1.9%, OR: 46.7), positive predictive value 98.44% and negative
      predictive value 86.44%. CONCLUSIONS: CA 125 measurements were more useful in the
      postmenopausal group. Higher CA 125 levels were observed in women with ovarian
      cancer diagnosis when compared to controls, in which lower CA 125 were observed.
      Higher sensitivity specificity and positive predictive values were observed in
      the postmenopausal group.

PMID- 20825053
TI  - The influence of a standardized soybean extract (Glycine max) on the expression
      level of cytochrome P450 genes in vivo.
AB  - OBJECTIVE: Soybean isoflavones are phytoestrogens that reduce menopausal symptoms
      and decrease the risk of certain chronic diseases, such as cancer and
      cardiovascular diseases. Despite the widespread use of soybean isoflavones as
      functional food and dietary supplements, data regarding the safety as well as
      herb-drug interactions, remain scarce. The aim of the study was to investigate
      the influence of soybean extract on the expression levels of cytochrome P450
      (CYP) genes using real-time PCR (RT-PCR). MATERIALS AND METHODS: Male Wistar rats
      were fed a standardized soybean extract containing 37% isoflavones (100 mg/kg)
      for 3 and 10 days. cDNA was synthesized from total RNA isolated from the liver
      using reverse transcription. The level of CYP genes expression was analyzed using
      RT-PCR method. RESULTS: Soybean extract administration resulted in a significant
      increase of CYP1A1 expression level compared with the control group (1.5-fold; p
      < 0.05). An inductory effect was also observed for CYP2D1 by 32% (p < 0.01) after
      10 days of treatment. No statistically significant differences were noted for
      CYPIA2, CYP2C6 and CYP3A2. In case of CYP3A1, the mRNA level of this gene was
      reduced by almost 35% (p < 0.05) both, after 3 and 10 days. CYP2D2 expression was
      also inhibited by the extract, but to a lesser degree when compared to CYP3A1.
      Moreover insignificant decrease of CYP2E1 expression level by 25% (p < 0.01) was
      observed after 3 days of treatment. CONCLUSIONS: These findings suggest that
      soybean extract may change the expression of CYP enzymes involved in
      biotransformation of xenobiotics (drugs, procarcinogens).

PMID- 20825054
TI  - [Evaluation of antenatal quality of life of hospitalized women with the use of
      Mother-Generated Index--pilot study].
AB  - OBJECTIVES: The objectives of this study included: (1) evaluation of the Polish
      version of Mother Generated-Index (MGI) as a tool for measuring antenatal Health
      Related Quality of Life (HRQL) of hospitalized women; (2) identification of
      factors influencing antenatal quality of life of hospitalized women; (3)
      assessment of correlations between MGI and SF-36v2, and between MGI and EQ-5D.
      MATERIAL AND METHODS: MGI is a three-step questionnaire. Respondents were asked
      to name important areas of life that had been affected by their pregnancy (step
      1) and then to assess, on the scale from 0 to 10, their positive or negative
      value (step 2). In Step 3, the women ranked the importance of the areas by
      allocating a total of 20 'spending points' among them. The sub-index MGI1 is
      defined as the mean of the Step 2 scores, the sub-index MGI2 is defined as the
      weighted mean of Step 2 scores with weights given in Step 3. Using SF-36v2, EQ
      5D, MGI questionnaires and socioeconomic survey we studied the HRQL of 99
      pregnant women hospitalized in ICZMP in Lodz. RESULTS: Sub-index MGI1 was
      included between 1.83 and 10 with mean 5.86 (SD 1.71). Sub-index MGI2 was between
      0 and 10, with mean 6.70 (SD 2.34). Sub-indexes of MGI were significantly (p <
      0.05) positively correlated with EQ-5D and with sub-indexes of SF-36v2. The
      correlations are weak or moderate (between 0.2 and 0.4). The mean of the score
      given in the second part of MGI was 8.58 (SD 1.13) for positive comments, 2.63
      (SD 1.22) for negative comments, and 5.02 (SD 1.55) for neutral comments.
      Differences between positive, negative and neutral comments were statistically
      significant (ANOVA, p = 0.00). Among factors which influence antenatal quality of
      life, the respondents named relationship with partner and family attitudes
      towards pregnancy delivery and baby work and personal finances. CONCLUSIONS: (1)
      MGI should be treated as an additional tool for HRQL measurement, since it
      reflects the differences between expectations towards pregnancy and reality
      Multicultural factors can influence MGI. (2) MGI allows to identify factors which
      influence the antenatal quality of life, taking into account their importance.
      (3) There are statistically significant positive correlations between sub-indexes
      of MGI and sub-indexes of SF-36v2, and between sub-indexes of MGI and EQ-5D.

PMID- 20825055
TI  - [Review of anti-adhesion prophylaxis methods--the past and the present].
AB  - Formation of postoperative adhesions presents a serious and complex problem in
      clinical practice. Apart from standard surgical procedures, a variety of
      different substances to prevent adhesions is available, but no universal method
      has been developed so far Clinical trials and animal studies on preventing the
      formation of postoperative adhesions and substances that can have potential anti
      adhesive properties have been carried out for over one hundred years.
      Considerable discrepancies and ambiguities regarding research results, as well as
      a great number of anti-adhesive substances to be tested, demonstrate the scope
      and the nature of the problem. Recently new anti-adhesive fluids and
      pharmacological agents have been developed, which in preliminary observations
      seem to be almost perfect. The following paper reviews available literature on
      anti-adhesive methods and the authors' limited experience

PMID- 20825056
TI  - [Hormonal (levonorgestrel) emergency contraception--effectiveness and mechanism
      of action].
AB  - Periodic abstinence and coitus interruptus are the most popular methods of
      contraception in Poland. Recent studies have provided us with evidence that the
      so-called "menstrual calendar" may be much less effective than it was believed.
      In these circumstances, promotion and use of safe and truly effective
      contraceptives is very important for Polish women. Emergency contraception (EC)
      is a method which could be used even in cases when other contraception methods
      have failed. Mechanism of action of levonorgestrel used for EC and possible
      disturbances in the process of implantation of the blastocyst in the endometrium,
      remain the source of heated discussion among medical professionals. The latest
      publications provide us with evidence that the use of levonorgestrel in EC
      neither alters endometrial receptivity nor impedes implantation. Hormonal EC
      effectiveness is another hot topic of gynecological endocrinology and statistics.
      There is, however, no better, safer, and more ethically accepted method of
      preventing unwanted pregnancy for patients in need of postcoital contraception.

PMID- 20825057
TI  - New onset Addison's disease presenting as prolonged hyperemesis in early
      pregnancy.
AB  - A 32-year-old Caucasian was admitted at 14 weeks of gestation with hypotension
      and weight loss. Family members noted that she appeared "tired" prior to
      pregnancy Past medical history included primary hypothyroidism treated with
      thyroxine (100 microg/day). She had a healthy daughter aged 2.5 years who had
      been born small for gestational age. At about 8 weeks of gestation she started to
      vomit several times a day. She was treated with antiemetics and intravenous
      fluids. Following discharge she remained nauseated, weak and lightheaded and lost
      about 8 kg of weight. After readmission she appeared ill and dehydrated, BMI 16.6
      kg/m2, BP 90/60 mmHg supine, 70/50 mmHg upright (with faint-like sensation),
      normal heart sounds, chest clinically clear, abdomen soft and not tender
      Investigations revealed severe hyponatraemia (sodium 112 mmol/L), normal
      potassium level 4.3 mmol/L, normal renal function, TSH 1.31 microIU/mL (reference
      range (RR): 0.27-4.2), freeT4 1.99 ng/dL (RR: 0.93-1.7), freeT3 3.29 pg/mL (RR:
      2.57-4.43), anti-TPO antibodies 467 IU/mL (RR: <34)). She was hyperpigmented,
      hypotensive and hyponatraemic despite rehydration. Cortisol & ACTH, followed by a
      250 microg short Synacthen test were requested and revealed peak cortisol
      response of 17 nmol/L (RR: above 550 nmol/l) as well as high baseline ACTH (969
      pg/mL, RR: 0-46 pg/mL). She was started on hydrocortisone and felt tremendously
      better A diagnosis of Addisons disease was made (in view of hypothyroidism as a
      part of Autoimmune Polyglandular Syndrome type II). She was discharged on
      hydrocortisone and fludrocortisone replacement. Further during her pregnancy
      there was about two-week foetal growth delay. She, however delivered a healthy
      female infant at 36 weeks of gestation. CONCLUSIONS: New onset Addison's disease
      is rare in pregnancy but may present with prolonged vomiting and weight loss.
      Therefore adrenal failure should be included in the differential diagnosis of
      hyperemesis gravidarum.

PMID- 20825058
TI  - Pleomorphic rhabdomyosarcoma of the uterine corpus--a case report.
AB  - Pleomorphic rhabdomyosarcoma of the uterus is a rare malignant tumor. It is
      connected with postmenopausal abnormal vaginal bleeding and abdominal pain. We
      report a case of a 66-year-old postmenopausal woman diagnosed with abnormal
      vaginal bleeding and abdominal pain. Vaginal ultrasonography showed enlarged
      uterus, 82 mm x 64 mm in size. The patient underwent total abdominal hysterectomy
      and bilateral salpingo-oophorectomy with postoperative chemotherapy due to
      pleomorphic rhabdomyosarcoma of the uterus. The patient died 2.5 years after the
      surgery as a result of a rapid spread of the neoplastic process. The case of
      rhabdomyosarcoma, together with the review of the literature, is presented in the
      following work. We find that the rarity of this histological entity makes it
      particularly worthy of publication.

PMID- 20825059
TI  - [Recombinant factor VIIa for treatment of postpartum hemorrhage due to uterine
      atony].
AB  - BACKGROUND: Obstetric hemorrhage is a life-threatening situation for every mother
      and child. NovoSeven is a recombinant, activated factor VII which may be useful
      in the treatment of uncontrollable hemorrhage. It accelerates hemostasis by
      direct activation of the factor X. MATERIAL AND METHODS: The author presents her
      own experience with administration of NovoSeven at the Intensive Care Unit,
      Medical University Szczecin in the treatment of bleedings after standard methods
      failure. NovoSeven was given to patients in postpartum hemorrhage due to uterine
      atony who did not present any signs of haemostatic disorders. RESULTS: In all
      presented cases, bleeding symptoms abated and hemodynamic stabilization was
      obtained shortly after the drug administration. CONCLUSION: NovoSeven is a very
      effective agent in the treatment of postpartum hemorrhage.

PMID- 20825060
TI  - [Polish Gynecological Society Experts' position on the use of Pregnamedc zelazo
      in gynecology and obstetrics].

PMID- 20825061
TI  - Aphakic glaucoma after congenital cataract surgery with and without intraocular
      lens implantation.
AB  - PURPOSE: To evaluate the incidence and individual risk factors for the
      development of aphakic glaucoma after congenital cataract surgery. MATERIAL AND
      METHODS: We retrospectively reviewed the records of 113 eyes of children who
      underwent surgery for cataract between 1998 and 2002. Outcome variables studied
      included intraocular pressure, number of medication changes required over the
      course of the follow-up, and surgical interventions required. RESULTS: We
      enrolled 113 eyes who had cataract extraction with IOL (101 eyes), or lensectomy
      with anterior vitrectomy (12 eyes). Median age during cataract surgery was 11.5
      months. The median time to development of postoperative glaucoma was 3.2 years
      (range, 6 months-10 years). Mean post cataract surgery follow-up was 6.2 years.
      Postoperative glaucoma developed in 9.7% of eyes of children with cataract.
      Postoperative open-angle glaucoma developed in 6 pseudophakic eyes and in 2
      aphakic eyes; postoperative closed-angle glaucoma developed in 3 aphakic eyes.
      The mean follow-up period after the diagnosis of glaucoma was 3.8 years. During
      the course of follow-up, all of 11 eyes required 1-3 medication changes for
      controlling glaucoma and 3 of them (31.4%), required surgical intervention.
      CONCLUSIONS: Despite modern surgical techniques the incidence of aphakic glaucoma
      must be considered in all patients after pediatric cataract extraction. Our
      results show the importance of careful follow up of intraocular pressure after
      cataract surgery in children. Young patients undergoing cataract surgery should
      be monitored routinely for glaucoma.

PMID- 20825062
TI  - [The evaluation of efficacy of Ahmed valve implantation in the surgical treatment
      of glaucoma in children and adolescents].
AB  - PURPOSE: To report the safety and efficacy of Ahmed glaucoma valve implantation
      in the management of secondary glaucoma in children and adolescents. MATERIAL AND
      METHODS: 6 patients with secondary glaucoma underwent Ahmed valve implantation. 1
      patient had aphakic glaucoma, 3 patients had traumatic glaucoma, 1 patient had
      aniridia and 1 patient had ectropion uveae. IOP values range from 35 to 51 mmHg
      (mean 41.3 mmHg), with maximal medical treatment by this time. Mean follow-up was
      2.17 years. RESULTS: Mean pooperative IOP ranged from 2 to 8 mmHg (mean 6 mmHg),
      during the first week. 6 months later IOP increased to 15.2 (6-21) mmHg. The mean
      IOP at last follow-up was 15 mmHg and overall success rate was 83.3%. We observed
      one hypotony, one tube exposure and one Tenon's cyst formation. CONCLUSIONS: The
      Ahmed valve is effective treatment for secondary glaucoma in children. It can be
      useful to avoid enucleation of the eye with traumatic glaucoma.

PMID- 20825063
TI  - Cataract surgery with primary intraocular lens implantation in children suffering
      from chronic uveitis.
AB  - PURPOSE: To evaluate the visual outcome of cataract surgery with intraocular lens
      (IOL) implantation in children with chronic uveitis. MATERIAL AND METHODS: The
      records of seven children (9 eyes), with chronic uveitis who had cataract
      extraction with IOL implantation between 2001 and 2007, were retrospectively
      examined. The mean follow-up was 47.9 months, respectively. The postoperative
      visual outcome and complications were analyzed. RESULTS: The mean age of 2 girls
      and 5 boys was 17.4 years (range from 12 to 21 years). 5 patients had unilateral
      cataract. 6 patients underwent cataract extraction with IOL implantation, one
      patient underwent combined cataract surgery with IOL implantation and
      trabeculectomy. Median age at surgery was 17.7 years. At the final follow-up
      examination 8 eyes (88.9%), had improved visual acuity. The visual acuity was
      20/20 in one eye, 20/40 or better in 5 eyes and 20/50 in 3 eyes. Posterior
      capsule opacification was observed in 5 eyes, high intraocular pressure in 2 eyes
      and cystoid macular edema in 1 eye. CONCLUSIONS: The outcomes of cataract
      extraction with IOL implantation in children's eyes with chronic uveitis may be
      satisfactory. Correct time of surgery, adequate long-term preoperative and
      postoperative anti-inflammatory therapy may promote good results.

PMID- 20825064
TI  - [Surgically induced astigmatism after bimanual phacoemulsification through
      microincision and after standard phacoemulsification].
AB  - PURPOSE: The purpose was to compare surgically induced after bimanual
      phacoemulsification performed through a 1.7 mm superotemporal clear corneal
      microincision (B-MICS), and after coaxial phacoemulsification performed through a
      3.2 mm superotemporal clear corneal incision, calculated with various
      mathematical methods. MATERIAL AND METHODS: Group 1 consisted of 29 eyes after
      bimanual phacoemulsification performed through a 1.7 mm superotemporal clear
      corneal microincision. Group 2 consisted of 31 eyes after coaxial
      phacoemulsification performed through a 3.2 mm superotemporal clear corneal
      incision. Ophthalmic examination was performed preoperatively, 1 day, 7 days, 1,
      3 and 6 months postoperatively. We performed auto-refractometry, keratometry,
      tonometry and visual acuity testing (UCVA and BCVA). SIA was calculated using:
      vector method, vector decomposition, Cravy's and Naeser's method. RESULTS: There
      was no difference in mean UCVA and BCVA between the groups in the whole
      observation period. In vector method SIA did not differ significantly between the
      groups during the whole follow-up. In vector decomposition (C90 component), SIA
      was higher in group 2 than in group 1, one day and 1 month postoperatively.
      Cravy's and Naeser's method showed that SIA in group 2 was significantly higher
      as long as the 1-st month postoperatively. In the final examination, there was no
      significant difference in SIA values between the groups for all methods of
      calculations. CONCLUSIONS: Technique B-MICS through a 1.7 mm incision offers
      equally good functional results, as standard phacoemulsification through 3.2 mm
      superotemporal clear corneal incision. The SIA axis was more stable in
      microincision group in the whole follow-up period.

PMID- 20825065
TI  - [Early changes in the visual system connected with brain's aneurysm rupture].
AB  - PURPOSE: To evaluate frequency and type of early changes in the visual system
      connected with brain's aneurysm rupture. MATERIAL AND METHODS: 45 patient, 34
      women and 11 men, with subarachnoid hemorrhage (SAH) after brain's aneurysm
      rupture were enclosed in this study. To identify aneurysm, cerebral angiography
      as well as CT or MR angiography were applied. Conventional ophthalmologic
      examination and Doppler sonography of the retrobulbar vessels were performed in
      all patients before and two or three days after neurosurgical procedure. RESULTS:
      The mean age of patients with SAH was 47.6 years. Female/male ratio was 3:1. The
      most common site of aneurysm was at the origin of the middle cerebral artery
      (37.8%), or anterior communicating artery (28.9%). In 73.3% of patients aneurysm
      were asymptomatic at diagnosis. The rest patients had some prodromal symptoms,
      including ocular signs (wide pupil, opressive feeling on the globe, diplopia or
      visual disturbances), in 15% of one's. Sudden headache (80%), was the most
      characteristic symptom of brain aneurysm rupture. In 20% the first sign of SAH
      was loss of consciousness. Papilledema and intraocular hemorrhages occurred in 25
      patients (55.6%), and wide pupil in 4 person (8.9%). Among patients with
      hemorrhagic changes 3 person (6.7%), had Terson syndrome. CONCLUSIONS: Female
      gender seem to increase the risk for intracranial aneurysm formation. Among
      symptoms, which are presenting manifestations of brain's aneurysm, ocular signs
      play the important role. Brain's aneurysm rupture is always connected with severe
      neurological symptoms. More than half of patients with SAH after intracranial
      aneurysm rupture have fundal hemorrhagic changes in fundus.

PMID- 20825066
TI  - [Focal retinal pigment epithelium proliferation as a risk factor for occult
      choroidal neovascularisation].
AB  - PURPOSE: To evaluate the relationship between isolated focal retinal pigment
      epithelium (RPE) proliferation and development of occult choroidal
      neovascularisation. MATERIAL AND METHODS: The natural clinical course of 43 eyes
      of 39 patients was analyzed. Patients with RPE proliferation as an isolated
      manifestation of retinal degeneration were included in this study. The mean age
      of patients was 75.0 (69-94). The mean observation period was 41.4 months (6-63).
      RESULTS: In 30 eyes (70%), occult choroidal neovascularisation occurred, in 13
      eyes (30%), that complication was not observed. The development of
      neovascularisation was correlated with the presence of neovascular membrane in
      the fellow eye. CONCLUSIONS: Based on presented data we can estimate that
      isolated focal proliferation of retinal pigment epithelium is an important risk
      factor for the development of occult choroidal neovascularisation.

PMID- 20825067
TI  - [Acute posterior multifocal placoid pigment epitheliopathy (APMPPE)--a
      therapeutic dilemma].
AB  - PURPOSE: To present a rare idiopathic inflammation of the posterior segment of
      the eye - acute posterior multifocal placoid pigment epitheliopathy (APMPPE).
      MATERIAL AND METHODS: A 17 years old male patient was referred to the Department
      of Ophthalmology of Medical College, Jagiellonian University in Krakow with the
      diagnosis of bilateral choroiditis of unknown etiology. The patient underwent the
      basic ophthalmological examination followed by fluorescein (FA) and indocyanine
      green (ICGA) angiography. Laboratory testing for Lyme disease, sarcoidosis and
      syphilis, as well as genetic testing, to determine the presence of HLA antigen
      complex, were performed RESULTS: Based on the outcomes of performed
      investigations the definitive diagnosis of APMPPE was established. Systemic
      steroidotherapy was initiated due to rapid progression of the inflammatory
      changes, progression of the central visual field changes and profound visual
      acuity deterioration. CONCLUSIONS: APMPPE is a rare, inflammatory and idiopathic
      eye disease with no clear indications for pharmacological therapy. However
      decision about necessity and sort of pharmacological therapy should be taken
      under consideration individually for each patient. ostra tylna wieloogniskowa
      plackowata epiteliopatia barwnikowa, steroidoterapia. acute posterior multifocal
      placoid pigment epitheliopathy, steroidotherapy.

PMID- 20825068
TI  - [Neuroretinitis in cat scratch disease].
AB  - PURPOSE: To present two cases of neuroretinitis in cat scratch disease We present
      two girls treated in Department of Ophthalmology of Poznai University of Medical
      Sciences because of unilateral, painless decrease of vision. Both patients
      presented following cat exposure fever and lymph nodes swelling. Ophthalmoscopic
      findings was neuroretinitis (optic disc edema with the macular star). Bartonella
      henselae antibody titers (IgG) were elevated. CSD is usually self-limited
      infection in immunocompetent patients and there is no clear treatment
      recommendations. One of our patients received treatment which included oral
      antibiotic (macrolides) and steroid. The second patient was left without
      treatment. In our case--the duration of visual loss was longer in patient who was
      not treated.

PMID- 20825069
TI  - [Annette von Droste-Hulshoff syndrome--case report].
AB  - PURPOSE: Annette von Droste-Hulshoff syndrome is characterized by
      pseudostrabismus due to macular ectopy in retinopathy of prematurity. The aim of
      the study is to present the case of Annette von Droste-Hulshoff syndrome.
      MATERIAL AND METHODS: Fourteen years old girl was referred to the Outpatient
      Clinic of the Department of Ophthalmology of University of Medical Sciences in
      Poznan in order to attain qualification to surgical treatment of divergent
      strabismus of her left eye. Divergent strabismus of the left eye was diagnosed in
      early childhood. The girl was born in 32-nd week of twin pregnancy with a birth
      weight 1520 g. Her corrected vision was 1.0 for each eye with an apparent
      exotropia of both eyes and normal position of the head. The Hirschberg test
      revealed corneal reflex shifted to the nasal margin of the pupil. On eye fundus
      examination temporal pulling of vessels and temporal displacement of macula was
      noted in each eye. Kappa angle value was +8 degrees for each eye. RESULTS:
      Pseudoexotropia due to temporal macular ectopy was diagnosed (in the course of
      suffered ROP). The girl was not qualified to surgical treatment. CONCLUSIONS:
      This case emphasizes fundamental importance of correct diagnosis and
      qualification to surgical treatment of strabismus.

PMID- 20825070
TI  - Optical coherence tomography in imaging of macular diseases.
AB  - OCT (opitcal coherence tomography), is a diagnostic method that enables the
      analysis of the retinal structures by means of high-resolution tomographic cross
      sections of the retina. Whereas fluorescein and indocyanine angiography allow
      visualization of the retinal epithelium layer and chorioretinal vessels, OCT may
      help in diagnosing and monitoring the condition of many internal retinal layers.
      Ultrasound B-mode examinations have a resolution of about 150 microm while OCT
      provides a resolution of 10 microm. OCT makes it possible to detect and measure
      morphological changes, retinal thickness, retinal volume, thickness of retinal
      nerve fiber layer and various parameters of the optic disc. We use OCT in the
      analysis of the retinal structures in various pathologies such as macular holes
      and pseudo-holes, epiretinal membranes, macular edemas of various origins,
      including vasooclusive disease and diabetic macular edema, lesions of
      vitreoretinal interface and vitreoretinal traction, serous and hemorrhagic
      detachments of the retina and of pigment epithelium, age related macular
      degeneration, diabetic retinopathy, glaucoma. OCT is an examination that is fast,
      sensitive, reproducible, non-invasive, non-contact and easy to perform and
      interpret for a retinologist. The aim of this article is to present OCT
      principles and techniques as well as OCT interpretation and images of most common
      retinal diseases: age related macular degeneration--dry and wet form, retinal
      angiomatous proliferation (RAP), central serous chorioretinopathy, epiretinal
      membranes, macular holes, diabetic retinopathy.

PMID- 20825071
TI  - Safety of ranibizumab therapy in wet AMD and the role of vascular endothelial
      growth factors in physiological angiogenesis.
AB  - Vascular endothelial growth factor - A (VEGF-A), is a major factor implicated in
      choroidal neovascularisation (CNV) and therefore a target for therapeutic agents
      in wet age related macular degeneration (AMD). Ranibiuzumab (Lucentis) blocks all
      active isoforms of VEGF-A and the products of their degradation. It penetrates
      through all layers of the retina in order to reach the target tissue. It is
      quickly removed from the system and it is characterised by low level of
      immunogenicity. The essence of angiogenesis is formation of new vessels by
      branching and expansion of already existing ones. Angiogenesis is an important
      physiological process that takes place during the healing of wounds,
      reconstruction of hypoxic injury and reproduction. However some diseases such as
      cancer, arthritis, diabetes and neovascular AMD are associated with persistent
      unregulated angiogenesis. There is an important question whether binding vascular
      endothelial growth factors in wet AMD therapies using ranibizumab is correlated
      with the increase of the incidence of systematic adverse effects (AEs), such as
      cardiovascular episodes or thrombosis. The aim of this article is to present
      ranibizumab as a safe drug in treating wet AMD patients. Even though the
      concentration of Lucentis administered in a dose of 0.3 or 0.5 mg into the
      vitreous body in the organism is very low, the incidence of AEs during the anti
      VEGF therapy was traced. In MARINA and ANCHOR studies, occurrence of possible AEs
      was observed. No statistically significant differences were shown in the AEs
      frequency between the patients treated with ranibizumab and the control group,
      and in correlation with the general population of patients suffering from wet
      AMD.

PMID- 20825072
TI  - [Novelty of vital dyes in ophthalmic surgery].
AB  - The aim of this paper is to present recent developments in the area of novelty of
      vital dyes in intraocular surgery. The authors present the advantages and
      disadvantages of several vital dyes currently used in ophthalmic surgery. Vital
      dyes are used to allow better intraoperative visualization of both the anterior
      and posterior segments. Indocyanine green and trypan blue are the most frequently
      used and the most efficacious dyes for staining the important anatomic areas but
      often are associated with significant side effects. These dyes are used in
      cataract and vitreo-retinal surgery. Other dyes including rhodamine 6G, E68,
      bromophenol blue, light green and Chicago blue are still under preclinical
      assessment.

PMID- 20825073
TI  - [Abnormal pupils' reactions].
AB  - Examination of the pupils' light reaction and estimation of the pupils' diameter
      are the components of the routine physical examination of a patient. Disturbances
      in pupils' light reaction, unequal size of the pupils indicate damage of the
      nervous system and require careful diagnosis, both neurological and
      ophthalmological. Different aspects of anatomy, physiology and the most common
      pathological syndromes associated with disturbed pupils' light reaction and
      unequal diameters of the pupils were presented in the article. Early diagnosis
      and proper treatment can allow to improve prognosis in the analyzed patient
      group.

PMID- 20825074
TI  - [Amoebas of the genus acanthamoeba as an etiological factor of keratitis].
AB  - PURPOSE: The aim of the paper was to describe the role of amoebas of the genus
      Acanthamoeba in the pathogenesis of keratitis. MATERIAL AND METHODS: A review of
      literature concerning the role of amoebas of the genus Acanthamoeba in the
      pathogenesis of keratitis was done. RESULTS: Amoebas of the genus Acanthamoeba
      can be widely found in soil, air, fresh as well as saline water and as
      facultative parasites in humans. Amoebas of this genus are responsible for the
      creation of Acanthamoeba keratitis. In this paper the latest data concerning the
      epidemiology, diagnostic and treatment of Acanthamoeba keratitis have been cited
      and disscused. CONCLUSIONS: 1. Keratitis induced by amoebas of the genus
      Acanthamoeba are characterized as acute and difficult to treat. 2. Acanthamoeba
      keratitis occurs in recent years more often due to the fact that more people wear
      contact lenses.

PMID- 20825075
TI  - [Screening of selected parameters of visual system in children at the age of 6 to
      10 in Great Poland area].
AB  - PURPOSE: The goal of the work was to analyze parameters of visual system in
      children from Great Poland territory. Research covered: visual acuity and phoria
      at distance, stereo near vision, colour vision, near point of convergence, plus
      lens test. MATERIAL AND METHODS: 1138 children at the age of 6-10 years were
      examined, including 88 students in their spectacles. During the examination C
      Landolt plates, +1.00 lens, Titmus Stereo Fly test, Ishihara plates, fixation
      ball and Maddox rod were used. RESULTS: At least 70% children passed particular
      tests, but the whole examination was passed by only 40% children (in glasses 45%
      and 15%, respectively); among children who failed plus lens test, 36% did not
      pass stereotest; 12% of children (35% in glasses), failed stereotest and reached
      different visual acuity in both eyes, which can cause binocular dysfunction.
      CONCLUSIONS: It is necessary to expand the scope of the school vision screening
      in school children using additional parameters connected with far and near vision
      and binocular vision.

PMID- 20825076
TI  - [Posterior selective rhizotomy in the treatment of severe spastic syndrome in
      cerebral palsy].
AB  - BACKGROUND: Aim of this study was to optimize surgical technique of posterior
      selective rhizotomy for prevention of possible complications. MATERIALS AND
      METHODS: 11 patients (age 3-30 years) with severe spastic tetraparesis due to
      cerebral palsy were operated. Muscle tone in lower limbs reached 4-5 points
      (Ashworth scale). In all cases posterior selective rhizotomy of L1-S1 spinal
      roots was performed using laminoplasty and intraoperative electromyographic
      monitoring. Results were assessed in early postoperative period and during follow
      up. RESULTS: In all cases in the early postoperative period we observed decrease
      of muscle tone to 1-2 points and increase of volume of passive movements. In the
      follow-up period 4 patients developed improvement of locomotor status, in 6 no
      changes were observed. In 1 case spastic syndrome recurred. We had no
      complications due to orthopaedic deformities of spinal column, sensory and pelvic
      disorders, muscular hypotonia. CONCLUSION: Posterior selective rhizotomy may be
      the method of choice in treatment of patients with severe spastic forms of
      cerebral palsy. Application of optimized surgical technique (laminoplasty,
      intraoperative stimulation electromyography) allows to decrease the risk of
      possible complications.

PMID- 20825077
TI  - [Tethered cord syndrome in different types of spina bifida in children].
AB  - BACKGROUND: Tethered cord syndrome (TCS) occurs in 10-75% of children after
      correction of myelomeningocele and lipomyelomeningocele. Early diagnosis and
      surgical treatment of TCS after correction of different types of spina bifida
      remains a challenging problem of modern neurosurgery. MATERIALS AND METHODS:
      Since January till December 2008 in Burdenko Neurosurgical Institute 15 children
      were prospectively examined and operated. All of them had TCS after surgical
      treatment of spina bifida: myelomeningocele--7 (47%), lipomyelomeningocele--4
      (27%), meningoradiculocele--1 (7%), meningocele--2 (13%), diastematomyelia--1
      (7%). In the analyzed series peak of TCS manifestation was within 4 and 12 years.
      RESULTS: Clinical presentation of the disease consisted of neurological,
      urological, proctological and orthopaedic syndromes. In the postoperative period
      positive results were observed in most cases: regression of pain syndrome in 7
      cases (87.5%), increase of muscle strength--in 4 (57%), improvement of sensory
      function--in 2 (33.3%), full or partial improvement of bladder and rectal
      function--in 4 (33.3%) and 5 (41.7%), respectively. Surgical complications
      occurred in 7 patients (46%): would CSF leak in 3 (20%), pseudomeningocele in 1
      (6.7%), transient urinary retention in 2 (13.3%), wound insufficiency due to CSF
      leak in 1 (6.7%), motor deterioration in 1 (6.7%). CONCLUSION: Early surgical
      treatment of TCS in most cases leads to stabilization or improvement of
      neurological status. Risk of surgical complications associated with CSF leak
      indicates that optimal ways of their prevention should be developed.

PMID- 20825078
TI  - [Rare observation of hyperostotic cranial lesions in osteogenesis imperfecta].
AB  - A rare case of hyperostotic skull deformity in a patient with congenital bone
      defect--osteogenesis imperfecta--is described. In this case typical symptoms
      encountered in adults were observed: decreased body length caused by shortened
      extremities due to multiple pathological fractures in childhood, deformities of
      thorax, spine, facial bones and teeth, skull lesions with craniobasal and
      brainstem symptoms, bluish hue of sclera, hypoacusis etc.). In this patient non
      typical abnormalities were found: visual deficit due to optic nerve atrophy
      caused by bilateral optic canal stenosis on the background of densitometrically
      proven hyperostotic skull base deformity.

PMID- 20825079
TI  - [Melanotic schwannoma of C(III) spinal root].
AB  - We present a case report of the very rare tumor--melanotic schwannoma. Since its
      first description on 1932 only approximately 100 cases were reported in
      literature. Due to intensive pigmentation and many features that common for
      metastatic melanoma and melanotic schwannoma differentiation between these tumors
      is a challenging and important problem. 61-year-old male patient underwent
      surgical removal of pigmented extramedullary mass lesion at C2-C3 level.
      Melanotic schwannoma was diagnosed on the basis of morphological and
      immunohistochemical signs. Despite positive expression of so-called 'melanoma
      markers', (HMB-45, S-100, Melana A) cells of melanotic schwannoma also express
      type IV collagen and laminin which are not characteristic for melanoma. In
      addition, Ki-67 is very low in melanotic schwannoma, thus it confirms benign
      character of this tumor. Mentioned immunohistochemical profile allowed to
      diagnose melanotic schwannoma. It is distinctly clear that prognosis in melanotic
      schwannoma is incomparably better than in melanoma. Surgical removal is the best
      treatment option, and postoperative radiation therapy is not necessary as in
      melanoma.

PMID- 20825080
TI  - [Diffuse hyperplasia of choroid plexuses of lateral ventricles].
AB  - Diffuse hyperplasia of choroid plexuses of lateral ventricles is extremely rare
      entity which is characterized by diffusely increased size of choroid plexuses
      along the entire choroid fissure and CSF hypersecretion. This disease, initially
      described by Davis in 1924, may be fallaciously diagnosed as bilateral
      choroidpapillomas. We present a case of diffuse hyperplasia of choroid plexuses
      of lateral ventricles in a female infant.

PMID- 20825081
TI  - [Comatose state caused by seizure-free status epilepticus in postoperative
      period].
AB  - We present a rare clinical observation of progressive development of neurological
      symptoms up to comatose state in a child with extra-intraventricular
      craniopharyngioma in delayed postoperative period due to seizure-free status
      epilepticus which was diagnosed only by EEG-monitoring. Concerning this case
      report, we discuss genesis of seizure-free status epilepticus and its possible
      role in development of severe condition in patients with different kinds of
      neurosurgical pathology in postoperative period.

PMID- 20825082
TI  - [Physiology of CSF system and pathophysiology of hydrocephalus].
AB  - In the paper author briefly and distinctly presents basic physiological and
      pathophysiological concepts used in diagnosis and treatment of hydrocephalus,
      using modern literature data and his own experience.

PMID- 20825083
TI  - [Hypothermia of the spinal cord].
AB  - During recent decades many methods of spinal cord hypothermia (SCH) were
      developed. Nevertheless the problem of SCH in complex urgent care of patients
      with complicated spinal cord injuries remains unsolved as well as problems of
      tactics and techniques of hypothermia. Author suggests his own technique for
      intraoperative SCH in severe spinal cord injury. Own observations during the
      procedure were used as criteria for evaluation of effectiveness. Implementation
      of suggested technique is expected to increase quality of surgical treatment of
      patients with complicated spinal cord injury, to improve surgical outcomes and to
      decrease rate of disability.

PMID- 20825084
TI  - [Resection of the liver combined with chemotherapy for the optimization of
      treatment in patients with metastatic colorectal cancer].
AB  - Anatomic hepatic resection is considered now a "gold standard" in the treatment
      of patients, suffering metastatic colorectal cancer (CRR) because it secures 23
      35% survival solely and 35-58% in combination with chemotherapy. The immediate
      results of cornbined treatment and its impact on survival of patients, suffering
      CRR with hepatic metastases, were studied up. In Lvivskiy Oncological Centre and
      Zaporizhskiy Oncological Dispensary in 2000-2009 yrs there was conducted combined
      treatment of 60 patients, suffering metastatic CRR. Combined treatment consisted
      of the large bowel tumor extirpation, hepatic resection and adjuvant chemotherapy
      (ACT). Median of overall survival in patients after combined treatment conduction
      had constituted 24.1 mo. The trustworthy improvement of late follow-up results
      was stimulated by combined application of hepatic resection with ACT. Small rate
      of complications and low postoperative lethality were noted.

PMID- 20825085
TI  - [Application of the mesh implants in the patients with eventration].
AB  - The causes of occurrence and clinical signs of eventration were analyzed. Such
      hemostasis disorders as hypoproteinemia, anemia, avitaminosis, pneumonia,
      hyperglycemia, coagulopathy constitute a common factors predisposing to
      eventration development. There was established, that eventration always coexists
      with progressing intoxication. There were proposed the methods of operative
      interventions, using propylene mesh implantation, what permits to improve the
      results of the patients treatment significantly.

PMID- 20825086
TI  - [Pathogenesis of postoperative lumbar-lateral abdominal hernias and their
      allohernioplasty].
AB  - The results of histological investigation of musculo-aponeurotic tissues of
      lumbar-lateral abdominal portion were analyzed. There was established, that
      relaxation and atrophy of these tissues had occurred due to nervous structures
      and vessels cutting with consequent development of postoperative lumbar-lateral
      hernias. The plastic material fixation to the bearing structures of lumbar
      lateral portion of abdominal wall, specifically to posterior wall of m. rectus
      abdominis aponeurotic sheath and the twelve rib cartilage constitutes the
      peculiarity of surgical treatment of postoperative lumbar-lateral abdominal
      hernias. According to the data of investigation, in 119 of the first group of
      patients operated on there were no recurrences, in the patients of comparative
      group, operated on using the standard method of alloplasty, the recurrences had
      occurred in 8.9% of observations.

PMID- 20825087
TI  - [Application of a two-layer dynamic self-regulating alloplasty in treatment of
      patients for giant postoperative abdominal hernia].
AB  - A new technique of two-layer dynamical abdominal wall alloplasty was applied in
      2005-2008 in 10 patients, ageing (55.3 +/- 12.6) yrs old at average, for giant
      postoperative abdominal hernia, based on a G. Valenti principle of dynamical self
      regulating prosthesis and the method of temporary closure of operation wound,
      according to Wittmann Patch procedure. It was proved, that introduction of
      original technique of a two-layer dynamical self-regulating abdominal wall
      alloplasty permits to escape postoperatively the abdominal compartment syndrome
      development.

PMID- 20825088
TI  - [Postoperative abdominal hernias and adhesion peritoneal disease].
AB  - In 223 patients, operated on for postoperative abdominal hernia, which had
      occurred on the peritoneal adhesion disease background, there were studied the
      rules of an early adhesion ileus formation, depending on severity and
      localization of the adhesion process. There was elaborated and applied a complex
      of prophylactic measures, aimed at lowering the risk of such complication
      occurrence.

PMID- 20825089
TI  - [Abdominal cavity adhesions. Some issues of pathogenesis, prophylaxis and
      treatment].
AB  - The abdominal cavity adhesions (ACA) constitute frequent consequence of various
      abdominal cavity diseases and traumas and frequent cause of the abdominal
      adhesive disease and its complications. In spite of the known pathogenesis of
      ACA, the surgeons had failed throughout the decades of years to find out the
      measures and methods of its prophylaxis. There are several causes of such a
      situation and the main of them is that ACA in its origin constitutes a
      philogenetically developed defense biologic reaction of organism. Because of the
      fact, that an organism constitutes the self-regulated biological system, any
      external inputs (including the treatment), directed on qualitative or
      quantitative signs of these reactions, meet systemic counteraction and become
      annihilated. The forced overcome of such a counteraction may cause the
      development of severe systemic disorders in organism. The only prophylactic
      measures against ACA, which were already tested throughout the time, are the
      tactical and technical methods, promoting the reduction of severity of
      morphological changes in peritoneum and abdominal organs, thus causing reduction
      of natural reaction of organism. When the adhesions formation is inevitable it is
      necessary to apply surgical methods of governing such a process, and
      omentoparietopexy may constitutes one of such methods.

PMID- 20825090
TI  - [Changes of hemostasis system and activity of 5-nucleotidase in the blood of
      patients during an acute period after the brain contusion].
AB  - Craniocerebral trauma (CCT) is an actual problem of modern medicine due to its
      high mortality incidence. Changes in hemostasis system may complicate the disease
      course and to cause the disseminated intravascular clotting syndrome occurrence.
      Early diagnosis and correction of such disorders would permit to escape
      complications and to lower mortality. Thromboplastinemia constitutes the main
      cause of hypercoagulation in CCT. Enzyme 5-nucleotidase is closely connected with
      thromboplastin. The raising of this enzyme activity may constitute an early
      diagnostic sign of hypercoagulation.

PMID- 20825091
TI  - [Effect of antioxidants lipin and quercetin on indices of lipid peroxidation and
      antioxidant system in recipients of renal allotransplants].
AB  - Activation of the free-radical oxidation processes (FROP) in the environment of
      activity inhibition of antioxidant defense system (ADS) plays an important role
      in pathogenesis of an ischemic-reperfusion damage (IRD) of renal allotransplant
      (RAT), causes its dysfunction and shortens long-term survival. Along with
      standard measures there was proposed intraoperative intravenous administration of
      antioxidant "cocktail", containing preparations lipin and quercetin, to recipient
      before switching on the kidney into the blood circulation and further during 3-5
      days postoperatively. There were studied up the impact of lipin and quercetin on
      indices of peroxidal oxidation of lipids, and ADS activity of the RAT recipients
      in early postoperative period. There was established, that these preparations
      inhibit activity of the FROP, raise the ADS potential in the recipient organism,
      promoting IRD severity reduction of RAT and acceleration of its function
      restoration,

PMID- 20825092
TI  - [Hydrostream resection of the spleen in experiment].
AB  - Experimental investigation, using apparatus for hydrostream dissection of
      tissues, was conducted. The expediency of application of a high pressure liquid
      stream while performance of spleen resection in experiment was proved. The stages
      of the organ capsule formation and parenchyma restoration in different terms
      after the operation were determined.

PMID- 20825093
TI  - [Dynamics of ultrastructural changes in the capillary endotheliocytes of the
      ischemic extremity in rats after transplantation of hematopoietic stem cells from
      the human fetal liver].
AB  - Experimental investigation was performed on the rats, in which the extremity
      ischemia was simulated to assess the application efficacy of hemopoietic stem
      cells, obtained from the human fetus liver, with the objective of angiogenesis
      activation. The perspective of the method application with the objective to
      stimulate the angiogenesis processes de novo in ischemia of the extremity, was
      studied, using the electron microscopy methods.

PMID- 20825094
TI  - [Further improvement of apparatuses for the hemostasis, processing and treatment
      of the infected wounds using high-temperature stream].
AB  - The bleeding stoppage and the wound sanitation constitute an important problem of
      modern surgery. There is information presented concerning the apparatuses
      elaboration for the bleeding stoppage, processing of the soft living tissues
      wounds, including the infected, during surgical operations conduction, using high
      temperature stream of air. The data adduced about the apparatuses trial and
      preclinical investigations of the method, realized with their help, had confirmed
      a high efficacy of hemostasis and sanation effects as well as significant
      reduction of the wounds processing time.

PMID- 20825095
TI  - [Effect of doxorubicine and heterogenous electromagnetic and thermal fields on
      the nonlinear dynamics of carcinoma Guerin development].
AB  - While local hyperthermia application the intratumoral blood flow is enhancing,
      leading to oxygenation and vascular permeability for antitumoral medicines. The
      work objective was to investigate the dependence of the development kinetics in
      carcinoma Gereni (CG) from combined action of doxorubicin (DR) and the kind of
      thermal impact, a contact one--due to a contact delivery of heat from a water
      heater and without contact - due to the tumor electromagnetic irradiation (EMI)
      using heterogenous electromagnetic field (EMF). DR was injected to the animals in
      a mass concentration of 1,5 mg on 1 kg of their body mass. The DR injection, a
      contact heating and EMI were started on the 8th day after the tumor reinoculation
      and kept on conducting once a 2 days. The course had included 5 injections and/or
      5 seances of a contact heating and/or EMF. The combined action of DR and EMI,
      using spatially heterogenous EMF of applicator in environment of physiological
      hyperthermia, have had influenced mostly the inhibition of a nonlinear dynamics
      in CG development. Antitumoral action of DR in the animals with CG was influenced
      by thermal and nonthermal effects, which were initiated by spatially heterogenous
      EMF. Nonlinear dynamics of a CG development in animals did not depend from
      horizontal direction of isolines of a spatially heterogenous EMF of inductive
      applicator towards the tumor and duration of the irradiation procedure (15 or 30
      minutes) after DR injection. The data obtained were exploited in clinical
      practice for the inductothermy optimal regimes elaboration while conducting
      complex treatment of patients, suffering oncological diseases.

PMID- 20825096
TI  - [Possibilities of rational choice and application of autotissues for
      hermetization of the suture connections in biliary surgery].
AB  - The results of experimental investigation of peculiarities of morphological
      transformation course in autotissues under the influence of bile were adduced.
      There was proposed a choice of peritoneum as an optimal plastic material in
      conditions of possible deficiency of local tissues during biliary surgery
      performance.

PMID- 20825098
TI  - Nursing. Advanced-practice nurses poised for larger role.

PMID- 20825099
TI  - Patient safety. Med schools find that teaching a culture of safety starts on day
      1.

PMID- 20825100
TI  - Workforce. Hospitals offer flexible sehedules to boost morale, productivity.

PMID- 20825101
TI  - Other voices. Avoiding clinical conflicts. Interview by Matthew Weinstock.

PMID- 20825102
TI  - Capital equipment. Market for medical marts heats up.

PMID- 20825103
TI  - Patient care. To reduce ICU stays, get patients moving.

PMID- 20825104
TI  - Your not-so-new goal.

PMID- 20825105
TI  - Access.
AB  - Reform will boost health care coverage by adding 30 million previously uninsured
      people to the insurance rolls. At first glance, that would seem like a boon for
      hospitals, but the consequences won't be nearly as cut and dried as you might
      expect.

PMID- 20825106
TI  - For hospitals and meaningful use, context is everything.

PMID- 20825107
TI  - The 2010 AHA NOVA Awards.
AB  - Addressing pediatric asthma in the inner-city. Connecting uninsured patients with
      a medical home. Developing alternatives to emergency care for primary care. The
      winners of the AHA NOVA Awards make a difference in their communities.

PMID- 20825108
TI  - Improving quality from the bottom up.

PMID- 20825109
TI  - Wireless EMRs: patient data anytime, anywhere.
AB  - Electronically delivered patient information is only useful if it is actually
      used. Hospitals with advanced wireless IT systems give clinicians unlimited
      access.

PMID- 20825110
TI  - Infection prevention risk assessment.

PMID- 20825111
TI  - Something in common.

PMID- 20825112
TI  - 'Environmental' sources of Mycobacterium leprae: issues and evidence.

PMID- 20825113
TI  - A Mycobacterium leprae VNTR database.

PMID- 20825114
TI  - 'Money is the vehicle of interaction': insight into social integration of people
      affected by leprosy in northern Nigeria.
AB  - OBJECTIVE: This paper proposes a mechanism by which socio-economic rehabilitation
      (SER) reduces stigma in northern Nigeria following are-analysis of the
      transcripts of interviews conducted to evaluate the impact of SER on leprosy
      related stigma. DESIGN: The evaluation combined quantitative questionnaire (P
      scale) with qualitative interviews of 20 individuals affected by leprosy, five
      focus group discussions and 10 key informant interviews. From our data, we
      developed a leprosy-related stigma framework by integrating emerging themes with
      the construct of threat to group functioning to describe stigma processes
      experienced by people affected by leprosy in northern Nigeria. RESULTS: Findings
      revealed people affected by leprosy are less likely to be stigmatised because of
      leprosy impairments than for their incapacity to contribute to family/community
      finances. We also identified micro-credit loans and vocational training as
      elements of SER for reducing stigma through the mechanism of protecting
      individuals against the loss of social value, and by facilitating their continued
      engagement in daily social roles in the family/community. CONCLUSION: We propose
      that SER stimulates attitudinal change towards, and inclusion of people affected
      by leprosy by protecting individuals against the loss of social value and
      increasing their contributive capacity. We recommend further empirical testing of
      the proposed framework to ascertain its utility in other cultures.

PMID- 20825115
TI  - Impacts of the diagnosis of leprosy and of visible impairments amongst people
      affected by leprosy in Cebu, the Philippines.
AB  - PURPOSE: To quantify the impact of the diagnosis of leprosy and of visible
      impairments in people affected by leprosy. SUBJECTS AND METHODS: Three interview
      based questionnaires designed to measure activity limitation, participation
      restriction, and general self-efficacy were used to collect data from three
      Groups. Group 1: leprosy affected people with visible impairment, Group 2: newly
      diagnosed leprosy patients with no visible impairment, Group 3: patients with
      other skin diseases symptomatic for more than 1 month. RESULTS: One hundred and
      eight subjects were recruited. The subjects with visible impairments (Group 1)
      had higher levels of participation restriction than those with skin disease
      (P0.012), and participation restriction was similar between subjects in Groups 2
      and 3 (P0-305). The people in Group 1 (35 subjects) also reported significantly
      more activity limitation compared to the people in either Group 2 (35 subjects)
      or Group 3 (38 subjects) (P 0-001, respectively). The subjects in Group 2 had no
      significant activity limitation compared with those in Group 3 (P0.338). A
      multivariate analysis showed that severe visible impairment was a risk factor for
      activity limitation (odds ratio 5.68, 95% CI: 1.09-297, P0.039) and a low level
      of self-efficacy (Odds ratio 6.38, 95% CI: 1.06-38.3, P0-043) among people
      affected by leprosy. CONCLUSION: Visible impairments affected the activities and
      attitudes of people affected by leprosy. However, others without visible
      impairment, had activity limitations, participation restrictions and levels of
      general self-efficacy that were similar to patients with other skin diseases.
      Prevention of visible impairments should be considered a key intervention for
      stigma reduction.

PMID- 20825116
TI  - Integration of leprosy in general health system vis-a-vis leprosy endemicity,
      health situation and socioeconomic development: observations from Chhattisgarh &
      Kerala.
AB  - This study looked at the integration of leprosy services in the GHS in context of
      health and socioeconomic situations using predefined indicators. It also looked
      at clients' perception of MDT services. The Indian states of Chhattisgarh and
      Kerala, which are at two extremes in leprosy endemicity, health situation and
      socioeconomic development, have been compared using predefined integration
      indicators related to the training of health workers, availability of MDT
      services, maintenance of MDT stock and involvement of Sub-centres in leprosy
      care. Data was collected by surveys of health facilities, sub-centres and
      communities in the two states, during 2006-2007. Information was collected by
      interviewing health personnel and clients, checking of records and on the spot
      observations using specifically designed formats. Results showed that integration
      is more inclusive in Chhattisgarh and has reached up to Sub-centre level. Both
      the community and health systems are sensitive and responsive to leprosy as it is
      perceived to be a major public health threat. But in Kerala, despite integration,
      it continues as a vertical programme with dependence on specialists and districts
      hospitals for diagnosis and treatment. MDT stock management is even poorer.
      Clients' perception towards MDT services are similar in both states.

PMID- 20825117
TI  - A case of erythema nodosum leprosum reaction with diffuse alveolar haemorrhage,
      successfully treated by pulsed methylprednisolone.
AB  - ary We present a case of erythema nodosum leprosum (ENL) reaction with dse
      alveolar haemorrhage (DAH) in a patient who completely recovered with pulsed
      methylprednisolone. Our case illustrates that ENL could be a predisposing factor
      for DAH and a high dose of corticosteroid plays an important role in successfully
      treating such a patient.

PMID- 20825118
TI  - The history of Mycobacterium leprae Thai-53 strain.

PMID- 20825119
TI  - Adding quality to leprosy control: prevention of disability.

PMID- 20825120
TI  - The history of a leprosy sanatorium in India. A literature review.
AB  - OBJECTIVE: Karigiri was set up initially to be a sanatorium with a difference,
      and the objective of this review is to study whether this had been achieved.
      METHODS: A broad search of 43 various publications from Karigiri. RESULTS: Stigma
      towards leprosy lead to the creation of this sanatorium, and within 20 years of
      its existence it made a significant contribution to the knowledge and treatment
      of this disease through research, and provided skilled manpower for both India
      and other developing countries.

PMID- 20825121
TI  - National workshop on 'Best practices to ensure sustainable quality care for
      leprosy affected persons at the district level referral centres through general
      health care system'.

PMID- 20825122
TI  - Reporting standards for intervention effectiveness studies.

PMID- 20825123
TI  - Comparison of constraint-induced movement therapy and bilateral treatment of
      equal intensity in people with chronic upper-extremity dysfunction after
      cerebrovascular accident.
AB  - OBJECTIVE: We compared the effectiveness of constraint-induced movement therapy
      (CIMT) with bilateral treatment of equal intensity for chronic upper-extremity
      (UE) dysfunction caused by cerebrovascular accident (CVA). DESIGN: We conducted a
      2-group, randomized intervention trial with stratification by severity of UE
      dysfunction. Twelve community-dwelling adults were provided with 6 hr of
      occupational therapy for 10 days plus additional home practice. Six participants
      wore a mitt on the unimpaired UE, and 6 participants were intrusively and
      repetitively cued to use both UEs. The Wolf Motor Function Test (WMFT) and the
      Canadian Occupational Performance Measure (COPM) were administered before and
      after treatment and at 6-mo follow-up. RESULTS: Significant improvements were
      found in WMFT and COPM scores across time in both groups. No significant between
      group differences were found on the WMFT. CONCLUSION: High-intensity occupational
      therapy using a CIMT or a bilateral approach can improve UE function in people
      with chronic UE dysfunction after CVA. Treatment intensity rather than restraint
      may be the critical therapeutic factor.

PMID- 20825124
TI  - Pilot study to examine the use of self-generation to improve learning and memory
      in people with traumatic brain injury.
AB  - People with traumatic brain injury (TBI) experience memory and learning
      difficulties. Difficulty in the initial acquisition of information is a primary
      reason people with TBI experience difficulties in learning and memory. Treatment
      focusing on improving the acquisition of information will likely improve both
      recall and recognition performance. In the "generation effect," items self
      generated are remembered better than items read or otherwise provided. The
      purpose of this study was to examine the application of the generation effect in
      improving memory for functional activities. The study used a within-subjects
      design and included 10 participants with TBI and 15 healthy control participants.
      Results demonstrated that material learned under the generated learning
      conditions was recalled better than when generated under provided learning
      conditions. This finding was true in both the TBI and the control groups. These
      results provide initial evidence supporting the use of self-generation to improve
      new learning of functional tasks for people with TBI.

PMID- 20825125
TI  - Development of a community mobility skills course for people who use mobility
      devices.
AB  - OBJECTIVE: We assessed mobility device skills in a lived-in environment on a
      community mobility skills course (CMSC) and related those skills to previously
      demonstrated skills in a controlled environment on an inside mobility skills
      course (IMSC). METHOD: Six mobility device users were selected from 91 adults who
      had previously completed the IMSC. Each of the following device groups was
      represented: power wheelchair, manual wheelchair, scooter, cane, crutch, and
      walker. CMSC tasks were modified from IMSC tasks and designed using materials in
      the community. RESULTS: All participants completed at least half of the CMSC
      tasks faster than they completed the corresponding IMSC tasks. The number of
      tasks on which participants improved and the amount of improvement varied by
      difficulty of task and mobility device used. CONCLUSION: Some mobility device
      skills used in controlled environments appear to transfer to community settings;
      others do not. Skills required for community participation may partially depend
      on mobility device used.

PMID- 20825126
TI  - Interrater and intrarater reliability of finger goniometric measurements.
AB  - Intrarater and interrater reliability were determined for middle finger range of
      motion (ROM) using the Rolyan finger goniometer. Seven raters measured ROM 3
      times (trials) on 20 healthy adults. Intraclass reliability analysis and analysis
      of variance was used to assess the consistency and stability of measures. Level
      of significance was set at p < or = .05. Significant differences (p < .05)
      existed between raters for metacarpophalangeal, proximal interphalangeal, and
      distal interphalangeal active finger ROM measurements and for metacarpophalangeal
      and proximal interphalangeal passive range of motion. Intrarater reliability
      ranged from .43 to .99 (single measure intraclass coefficient). Interrater
      reliability ranged from .24 to .95, with passive measures lower than active
      measures. These results provide clinicians with evidence for using this specific
      goniometer and issues associated with various therapists assessing finger ROM.

PMID- 20825127
TI  - Consistency and construct validity of the Activity Card Sort (modified) in
      measuring activity resumption after stem cell transplantation.
AB  - OBJECTIVE: We assessed the psychometrics of a self-administered survey
      modification of the Activity Card Sort (modified; ACSm) when used to track
      activity resumption after stem cell transplantation (SCT). METHOD: Thirty-six
      participants completed the ACSm for a descriptive pilot study of recovery after
      SCT. Reliability was assessed by determining the longitudinal consistency of
      participants' designation of an activity as never done versus done previously and
      by calculating internal consistency. Construct validity was assessed by
      correlating the ACSm scores with measures of quality of life, performance status,
      and perceived cognitive impairment. RESULTS: Participants gave consistent
      designations for 72% of items. Internal consistency of the total score was alpha
      > 0.86 at all assessments. The ACSm scores were correlated with quality of life
      (r = 0.51, p = .0019), functional well-being (r = 0.59, p = .0002), and
      performance status (r = 0.42, p = 0.011) and not associated with cognitive
      impairment (r = .22, p = .19). CONCLUSION: The ACSm demonstrated provisional
      evidence of reliability, internal consistency, and construct validity.

PMID- 20825128
TI  - Cognitive, visual, auditory, and emotional factors that affect participation in
      older adults.
AB  - OBJECTIVE: To determine whether changes in hearing, cognition, depression, and
      vision affect daily life participation and whether screening tests that identify
      problems could be used in the home. METHOD: Interviewers assessed presence of
      medical conditions, social class, distance acuity, cognition, hearing,
      depression, and participation using valid screening tools. Participation scores
      were subgrouped according to negative or positive results. Multiple regression
      analysis determined association of screening tests with participation. RESULTS:
      Eighty-eight older adults, ages 62-90, participated. Positive screening tests
      were found in 43% of participants for distance acuity, 9% for cognitive problems,
      8% for depression, and 15% for hearing loss. Relationships were found among age,
      cognition, depression, and vision and participation. CONCLUSION: Mild levels of
      decreased vision, depression, and decreased cognition are associated with lower
      participation. These conditions can be screened by occupational therapists and
      managed to help older adults remain active and maintain their health.

PMID- 20825129
TI  - In-Home Occupational Performance Evaluation (I-HOPE).
AB  - OBJECTIVE: We describe the development and preliminary psychometric properties of
      an assessment to quantify the magnitude of an environmental barrier's influence
      on occupational performance. METHOD: The assessment was developed and then
      piloted on a group of 77 older adults before and after an occupational therapy
      intervention focused on environmental barrier removal. Refinements were made to
      the assessment before it was evaluated for interrater reliability in a sample of
      10 older adults using 2 raters. RESULTS: The In-Home Occupational Performance
      Evaluation (I-HOPE) is a performance-based measure that evaluates 44 activities
      in the home. The 4 subscales of Activity Participation, Client's Rating of
      Performance, Client's Satisfaction With Performance, and Severity of
      Environmental Barriers are sensitive to change in the environment. The subscales'
      internal consistency from .77 to .85, and intraclass correlation coefficients
      ranged from .99 to 1.0. CONCLUSION: This preliminary study suggests that the I
      HOPE is a psychometrically sound instrument that can be used to examine person
      environment fit in the home.

PMID- 20825130
TI  - Description of dementia caregiver uplifts and implications for occupational
      therapy.
AB  - OBJECTIVE: Most occupational therapy interventions for caregivers are designed to
      reduce negative consequences of caregiving by building skills to manage problem
      behaviors and dependence. However, therapists may be missing an opportunity to
      provide interventions that directly help caregivers to emphasize and act on
      positive aspects of care. We describe care-related thinking and action processes
      of long-term caregivers who report positive effects related to caring for a
      spouse with dementia. METHOD: We analyzed data from 15 experienced and uplifted
      (reporting improved well-being from caregiving) spouse caregivers to describe how
      they think about and carry out their care duties. RESULTS: We describe two
      primary themes of caregiver thinking and action: (1) engaging in positive
      behaviors and (2) making adjustments in attitudes. CONCLUSION: These findings
      support a new focus for occupational therapy caregiver intervention that promotes
      a positive approach to thinking about and enacting care tasks.

PMID- 20825131
TI  - Effect of seated position on upper-extremity access to augmentative communication
      for children with cerebral palsy: preliminary investigation.
AB  - OBJECTIVE: Our goal in this study was to determine the effect of seated position
      on upper-extremity access to augmentative communication for a child with cerebral
      palsy. METHOD: A single-subject ABAB design was used with one 5-yr-old
      participant. We compared accuracy and speed of selection of targets on a speech
      generating device in the participant's typical position and in an intervention
      position. The intervention position conformed to current clinical conventions and
      research on promoting upper-extremity movement. The intervention position was
      achieved through simple modifications to the participant's typical seating.
      RESULTS: Accuracy of target selection was moderately improved in the intervention
      position compared with the typical position. CONCLUSION: Results provide
      preliminary empirical evidence of the positive effects of functional seating on
      access to augmentative communication for children with cerebral palsy. Further
      research is required to confirm the positive effect of the intervention position
      across other people who use augmentative communication.

PMID- 20825132
TI  - Children's and parents' perspectives about activity performance and participation
      after spinal cord injury: initial development of a patient-reported outcome
      measure.
AB  - OBJECTIVE: To report on a cognitive testing study on newly constructed items
      designed to evaluate client-reported outcomes of activity performance and
      participation after spinal cord injury (SCI). METHOD: Thirty-three children with
      SCI and 13 caregivers participated in cognitive testing interviews. Open-ended
      questions were used to gain a better understanding of activity performance and
      participation. The interviews were transcribed verbatim. A thematic analysis was
      carried out independently by 2 researchers, and key sentences and phrases from
      both analyses were merged. RESULTS: Four themes were defined: (1) apprehension
      related to activity performance and participation, (2) reference point, (3)
      missing out, and (4) autonomy. CONCLUSION: Insight into children's and
      caregivers' perspectives provided important information that helped refine the
      wording of test items and response scales. The theme of autonomy provided a
      stronger catalyst to solidify items for both child- and parent-reported outcomes.
      This study further validated the complexity of the construct of participation.

PMID- 20825133
TI  - Manual ability classification system for children with cerebral palsy in a school
      setting and its relationship to home self-care activities.
AB  - OBJECTIVE: Our aim in this study was to investigate the relationship between (a)
      the manual abilities of children with cerebral palsy (CP), assessed with the
      Manual Ability Classification System (MACS) in a school rehabilitation setting,
      and (b) the children's performance of self-care activities at home, assessed with
      the Pediatric Evaluation of Disability Inventory (PEDI). In addition, we assessed
      the interobserver reliability of the MACS. METHOD: Sixty-one children with CP
      were included (mean age = 10.3 yr, range = 5-14). The MACS was classified by 2
      independent raters. The PEDI was scored in a structured interview. RESULTS: The
      Spearman correlation coefficient between the MACS and the self-care domain of the
      PEDI Caregiver Assistance Scale was high and statistically significant (r = .72).
      The interobserver reliability of the MACS was good (weighted kappa = .86).
      CONCLUSION: The MACS is a reliable instrument in a school environment and is
      related to the performance of daily life self-care activities at home.

PMID- 20825134
TI  - Validity evidence for the Child Occupational Self Assessment.
AB  - To ensure that researchers and practitioners make valid interpretations from
      children's self-reports, evidence must demonstrate that the self-report has
      appropriate psychometric properties. The Child Occupational Self Assessment
      (COSA) is a self-report of occupational competence and value for everyday
      activities designed to involve children in identifying goals and assessing
      outcomes. Five hundred two children with disabilities, ages 6-17, completed the
      COSA. We used a Rasch Partial Credit model and parametric and nonparametric
      statistics to obtain validity evidence. Evidence suggests that the COSA has good
      content, structural, and substantive validity as given by item and child fit
      statistics and unidimensionality evaluation. Evidence for external validity was
      mixed because child fit status and measures varied with some demographic and
      assessment administration variables. Evidence suggests that most children's
      responses to the COSA can be validly interpreted as indicators of occupational
      competence and value for everyday activities.

PMID- 20825135
TI  - Reliability and validity of the Children's Leisure Assessment Scale.
AB  - OBJECTIVE: We examined the internal consistency and construct validity of the
      Children's Leisure Assessment Scale (CLASS), which measures multidimensional
      participation in children's and adolescents' leisure activities. METHOD: The
      questionnaire's content and face validity were first established, followed by a
      factor analysis of the CLASS's frequency domain of the responses of 249 children
      and adolescents. Internal consistency was evaluated for each of the factors, and
      construct validity was established by examining gender differences. RESULTS: The
      factors showed acceptable levels of internal reliability (Cronbach's alpha ranged
      from .57 to .83). We found that girls participated in significantly more self
      enrichment activities and instrumental indoor activities, with greater
      preference. However, boys participated in significantly more games and sports
      activities. CONCLUSION: The CLASS shows good internal reliability and may be
      useful in the future as a clinical and research tool in occupational therapy for
      evaluating leisure activities among typically developing children and
      adolescents.

PMID- 20825136
TI  - Maternal health after the birth of a medically complex infant: setting the
      context for evaluation of co-occupational performance.
AB  - OBJECTIVE: Physical and psychological health indicators of mothers who gave birth
      to medically complex infants were examined to explore potential risk factors for
      the development of chronic conditions and to develop a scholarly base that
      supports the inclusion of maternal health in the scope of early intervention
      practice. METHOD: Ten mothers completed the Perinatal Posttraumatic Stress
      Disorder Questionnaire and the State Trait Anxiety Form Y-1. Nine women completed
      24-h Holter recording. Frequency of symptoms of posttraumatic stress disorder
      (PTSD) and anxiety were determined. High frequency heart rate variability was
      examined for indicators of autonomic dysregulation. RESULTS: Nine of 10 women
      reported symptoms associated with PTSD, and 2 of these women reported more severe
      symptoms. Two women demonstrated indicators of autonomic dysregulation.
      CONCLUSION: Further research examining psychological and physical characteristics
      in mothers of infants at high risk is important to determine whether these women
      are at greater risk for chronic health conditions.

PMID- 20825137
TI  - Exploring the relation of health-promoting behaviors to role participation and
      health-related quality of life in women with multiple sclerosis: a pilot study.
AB  - OBJECTIVE: We examined the relation of health-promoting behaviors to
      participation in life roles and health-related quality of life (HR-QOL) in women
      with multiple sclerosis. METHOD: We used a correlational design. Frequency of
      health-promoting behaviors was obtained from the Health-Promoting Lifestyle
      Profile-II. Role participation was measured by the SF-36 Role-Physical, Role
      Emotional, and Social Functioning scales, and HR-QOL was measured with the
      Physical and Mental Component scales. RESULTS: Eleven significant positive
      correlations were found among specific health-promoting behaviors (e.g.,
      nutrition, stress management, physical activity, positive interpersonal
      relations, spiritual growth), role participation, and HR-QOL. CONCLUSION: The
      findings suggest that involvement in health-promoting behaviors is associated
      with greater participation in life roles and HR-QOL for women with multiple
      sclerosis. This study provides preliminary evidence for the use and development
      of health promotion in occupational therapy treatment.

PMID- 20825139
TI  - [Financial crisis and the public health system].

PMID- 20825138
TI  - Mental health evidence in the American Journal of Occupational Therapy.
AB  - We reviewed the mental health articles published in the American Journal of
      Occupational Therapy (AJOT) from 2008 through 2009 in light of meeting the
      Centennial Vision charge of supporting practice through evidence. Seven articles
      that addressed mental health practice were published in AJOT over these years.
      Review of the articles found that only two addressed effectiveness of
      occupational therapy intervention; one was rated as Level II evidence, and the
      other was rated as Level V evidence. Two articles addressed instrument
      development and testing. Three articles were basic research studies that expanded
      consideration about the needs of people with mental health conditions. Scholars
      and clinicians have begun to embrace the charge of the Centennial Vision to
      support practice with evidence and continue to embrace mental health practice but
      have a distance to travel. We hope that in the coming years, the profession will
      see more evidence published in AJOT supporting mental health as practiced by
      occupational therapists.

PMID- 20825140
TI  - [Perception among college students of the healthcare law against smoking].
AB  - OBJECTIVE: To understand smoking habits among college students and their opinion
      about the anti-smoking law. METHOD: Cross-sectional descriptive study conducted.
      Data gathering was carried out through surveys. RESULTS: Sample of 284 students.
      42.6% were smokers and 11.6% were ex-smokers. The heaviest smokers were among the
      24-29 age group and those who combined work and school. 13.2% did not perceive
      any risk in smoking, and 16.1% were unconcerned about the risks to passive
      smokers. 66.3% of smokers were worried about the effects of smoking on their
      health. Women perceived more than men that the anti-smoking law implementation
      was effective and was socially beneficial. Since the anti-smoking law came into
      effect, 16.5% of the sample had quit smoking and 35.5% had considered quitting.
      24.6% did not abide by the law. Agreeing with the law was correlated with being a
      non-smoker or an ex-smoker being between 18 and 23 years of age or older than 30,
      studying health sciences, perceiving that smoking creates health hazards and
      being female. CONCLUSION: These results are of interest because they facilitate
      the planning of specific activities targeted to this type of people, who in the
      future will become social points of references. Since smoking constitutes one of
      the biggest public health problems it should be tackled with a greater commitment
      from health and academic authorities, including assistance for those willing to
      quit smoking.

PMID- 20825141
TI  - [Shared security in the healthcare environment: negotiating the meanings of
      risk].
AB  - Some authors affirm that we live in a "risk society" and point through this
      statement at the awareness of danger that rules our time and legitimates the
      adoption of surveillance and control measures to guarantee security. Health
      services are not alien to this trend, though a biomedical instrumental view
      prevails consigning the individual to a passive position. In the light of Health
      Anthropology this article proposes a reflection about a kind of behavioural risk
      which forces the totality of professionals involved, to make negotiation become
      the central figure of the attention process. Shared security is a concept that
      makes sense within the encounter and negotiation space defined between the health
      professional and the patient. It assumes a relation based on dialogue, capable of
      overcoming the inequality among them. It refers to the adoption of participative
      strategies capable of diminishing the risks that arise from the lack of
      knowledge, the ability or will in valid and conscious individuals, not only for
      themselves but also for the others belonging to their environment. Negotiating
      the cultural meaning of illness becomes then the cornerstone of shared security.

PMID- 20825142
TI  - [Clinical practice and formation in community nursing].
AB  - Health is understood as a complex phenomenon, related to multiple causes linked
      to factors which have diverse biological, psychological, economic and social
      natures. Among these and individuals' behavior a causal relationship is
      established, converting those individual decision-making processes into
      fundamental health which bears evidence on the necessity for health professionals
      to be prepared for this new reality. Community nursing clinical contexts comprise
      the first line of priorities to deal with this problem. The objective of this
      article is to comprehend how the process to prepare nursing professionals for
      clinical practice in community nursing occurs in a Superior School of Nursing in
      Portugal. This study is of an exploratory and descriptive nature. Interviews were
      carried out and later their content was analyzed. Based on the results, the
      authors noticed the need to redirect teaching in order to form professionals who
      attend to the needs of the population, who work in teams, and who, mainly succeed
      in dialoging according to the Paulo Freire perspective. The authors conclude that
      it is necessary to create a greater coherence between what is taught and what
      occurs in the context of clinical practice, in other words, that the school world
      carries on a dialogue with the working, clinical practice world and vice versa.

PMID- 20825143
TI  - [Technical procedures for treating pain].
AB  - Nowadays, chronic pain treatment units are comprised by multidisciplinary work
      teams on which the contribution by each professional involved contributes to the
      team objective to handle and control pain. Out of all the forms of treatment and
      action plans developed for patients which deal with all the biological,
      psychological and social needs related to their experiences with chronic pain, in
      this article the authors concentrate exclusively on those technological and
      invasive procedures that are most frequently carried out by medical teams in
      chronic pain units. In this sense, nurses play an active participatory role in
      those procedures carried out, mainly in outpatient clinics where a patient is
      treated as an outpatient and nurses perform clinical services without the need of
      hospitalization.

PMID- 20825144
TI  - [Pain and suffering. Ethics aspects].
AB  - The understanding of pain and suffering have evolved throughout the different
      stages of history. In modern times, pain, thanks to scientific and technological
      advances has been dealt with more efficiently although there is still a long way
      to go towards the relief of suffering due to its complexity. Good nursing care
      requires nurses to have good training as well as having the ability to relate to
      patients. They also need professional maturity in order to deal with emotional
      problems arising from pain and suffering. New nursing theories place
      responsibility with the nurse when treating the challenges brought about by pain
      and suffering.

PMID- 20825145
TI  - [Diabetes mellitus in teenagers].
AB  - Diabetes Mellitus during infancy childhood or adolescence does not differ from
      adult diabetes mellitus in terms of basic principles nor therapeutic treatment
      methods but the characteristics patients have during those ages signify that
      diabetes has a special repercussion and becomes harder to treat in patients
      during those ages.

PMID- 20825146
TI  - [Preparing for the return from the holidays].
AB  - Opinion article in which authors reflect on the advantages and disadvantages of
      the holiday period, which is the return and the many situations they can be
      exposed to any of us.

PMID- 20825147
TI  - [Nursing in aquatic parks].
AB  - Based on his personal experience, the author explains the important role that a
      nursing professional can carry out in an aquatic park.

PMID- 20825149
TI  - Heats of formation of organic compounds by a simple calculation.
AB  - Heats (enthalpies) of formation of organic compounds are obtained by adding a
      constant for a functional group to the heat of formation of its hydrocarbon
      precursor obtained by counting hydrogens, as previously described. A single
      molecule is used to obtain the contribution of each functional group. Unlike all
      other empirical schemes, no global fitting is used. The calculation is done with
      pencil and paper or a hand calculator. The accuracy of the results is
      demonstrated by their agreement with more than 360 species of experimentally
      known heats of formation with a mean average deviation of 0.75 kcal mol(-1), very
      nearly equal to the mean experimental uncertainty. Alcohols, hydroperoxides,
      ethers, amines, ketones, aldehydes, carboxylic acids, esters, chlorides, phenols,
      anilines, aryl ethers, nitriles, amides, and alkyl radicals are used as examples
      of the method. This success allows the calculation of experimentally unknown
      heats of formation. The method is limited to compounds that are not subject to
      strain or effects of conjugation. In such cases, the experimental heat of
      formation of the hydrocarbon precursor may be used. The method can be extended to
      functional groups not treated here.

PMID- 20825148
TI  - Base-catalyzed isomerization of 2-isoxazolines enables a two-step
      enantioselective synthesis of beta-hydroxynitriles from enals.
AB  - The asymmetric synthesis of beta-hydroxynitriles remains a challenge in organic
      synthesis. Herein we report a convenient synthesis of beta-hydroxynitriles from
      enantiomerically enriched 3-unsubstituted 2-isoxazolines via a base-catalyzed
      ring-opening reaction that takes place without loss of enantiopurity. In
      combination with organocatalytic enantioselective synthesis of 3-unsubstituted 2
      isoxazolines, the ring-opening enables a short 2-step synthesis of beta
      hydroxynitriles from alpha,beta-unsaturated aldehydes in high enantiomeric
      purity.

PMID- 20825151
TI  - Macromolecular knot in good and poor solvents: a Monte Carlo simulation.
AB  - The probability and dimension of the simple macromolecular knots over a wide
      range of temperatures corresponding from good to poor solvents are investigated
      by Monte Carlo simulation. Macromolecular knots are modeled as rings of self
      avoiding walks on a simple cubic lattice with the nearest neighbor attractions.
      We found that there is a minimum probability for the unknotted ring at a certain
      temperature. The size dependence of trivial, trefoil, and figure-eight knots on
      chain lengths and temperatures is presented. The simulation results for the size
      dependence on the knot's complication in different solvents are in good
      qualitative agreement with prediction of the scaling model proposed by Grosberg
      et al. The critical exponent for long chain is independent of the knot types
      based on the simulation results, although the mean square radius of gyration is
      influenced significantly by the knot types for a shorter length macromolecular
      ring. We calculated the ratio of the topological invariant p of trefoil knot and
      figure-eight knot and found that the ratio is approaching to 1.3 with the
      increasing of the chain length.

PMID- 20825150
TI  - On catalytic preorganization in oxyanion holes: highlighting the problems with
      the gas-phase modeling of oxyanion holes and illustrating the need for complete
      enzyme models.
AB  - Oxyanion holes play a major role in catalyzing enzymatic reactions, yet the
      corresponding energetics is frequently misunderstood. The main problem may be
      associated with the nontrivial nature of the electrostatic preorganization
      effect, without following the relevant formulation. That is, although the
      energetics of oxyanion holes have been fully quantified in early studies (which
      include both the enzymatic and reference solution reactions), the findings of
      these studies are sometimes overlooked, and, in some cases, it is assumed that
      gas-phase calculations with a fixed model of an oxyanion hole are sufficient for
      assessing the corresponding effect in the protein. Herein, we present a
      systematic analysis of this issue, clarifying the problems associated with
      modeling oxyanions by means of two fixed water molecules (or related constructs).
      We then re-emphasize the point that the effect of the oxyanion hole is mainly due
      to the fact that the relevant dipoles are already set in an orientation that
      stabilizes the TS charges, whereas the corresponding dipoles in solution are
      randomly oriented, resulting in the need to pay a very large reorganization
      energy. Simply calculating interaction energies with relatively fixed species
      cannot capture this crucial point, and considering it may help in advancing
      rational enzyme design.

PMID- 20825152
TI  - Interfacial assemblies of atypical amphiphilic porphyrins:
      hydrophobicity/hydrophilicity of substituents, annealing effects, and
      supramolecular chirality.
AB  - Interfacial molecular assemblies of eight atypical amphiphilic porphyrins,
      substituted with hydrophobic or hydrophilic substituents but without long alkyl
      chains on their molecular skeletons, have been investigated in terms of
      supramolecular chiralty generation and amplification. It is found that all of the
      originally organized interfacial molecular assemblies display very weak or
      undetectable supramolecular chirality. Interestingly, for those porphyrins
      bearing hydrophilic substituents, it is found that their molecular assemblies
      display distinct supramolecular chirality when applying a thermal annealing
      treatment. In contrast, for those bearing hydrophobic substituents, the formed
      assemblies remain achiral after similar treatment. This investigation suggests
      that the hydrophobicity/hydrophilicity of the substituents of the atypical
      amphiphilies could affect the occurrence of the interfacial mirror symmetry
      breaking substantially. It discloses that, although some of the interfacial
      assemblies are superficially achiral, a thermal annealing treatment could endow
      them with evident supramolecular chirality.

PMID- 20825153
TI  - Benzotriazol-1-yl-sulfonyl azide for diazotransfer and preparation of
      azidoacylbenzotriazoles.
AB  - Benzotriazol-1-yl-sulfonyl azide, a new crystalline, stable, and easily available
      diazotransfer reagent provides N-(alpha-azidoacyl)benzotriazoles convenient for N
      , O-, C- and S-acylations. The efficient syntheses of various amides, azido
      protected peptides, esters, ketones and thioesters is reported together with a
      wide range of azides (including alpha-azido acids from alpha- amino acids in
      partially aqueous conditions) and diazo compounds.

PMID- 20825154
TI  - Patterning of hierarchically aligned single-walled carbon nanotube Langmuir
      Blodgett films by microcontact printing.
AB  - We present a patterning method for hierarchically aligned assembly of single
      walled carbon nanotubes (SWNTs) using a combination of the Langmuir-Blodgett (LB)
      technique and soft lithography. The LB technique allows one to control the
      alignment and the surface density of SWNTs by adjusting surface pressure of the
      film at the air-water interface. The aligned SWNT Langmuir films are successfully
      transferred onto the polydimethylsiloxane (PDMS) or silicon substrate with
      unidirectional alignment, and SWNT patterns with various shapes are fabricated on
      silicon and flexible poly(ethylene terephthalate) (PET) substrates by contacting
      and peeling off the PDMS stamp from the substrates via microcontact printing or
      lift-up methods. The SWNT patterning technique using the combination of soft
      lithography and the LB method can be applied in various fields, such as flexible
      high-speed transistors, high-efficiency solar cells, and transparent electrodes.

PMID- 20825155
TI  - An isolable bis-silylene oxide ("disilylenoxane") and its metal coordination.
AB  - The first isolable oxygen-bridged bis-silylene 1 has been synthesized by facile
      dehydrochloration of the corresponding disiloxane [LSiH(Cl)-O-SiH(Cl)L] precursor
      [L = PhC(NtBu)(2)] with LiN(SiMe(3))(2). Compound 1 contains three-coordinate,
      pyramidal Si(II) atoms in a bent disiloxane-like moiety and reacts readily with
      [Ni(COD)(2)] to afford the unique bis-silylene oxide nickel complex 3.

PMID- 20825157
TI  - Gluten protein composition in several fractions obtained by shear induced
      separation of wheat flour.
AB  - Recently, it was found that applying curvilinear shear flow in a cone-cone
      shearing device to wheat flour dough induces separation, resulting in a gluten
      enriched fraction in the apex of the cone and gluten-depleted fraction at the
      outer part. This article describes whether fractionation of the various
      proteineous components occurs during and after separation of Soissons wheat
      flour. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and
      size-exclusion high performance liquid chromatography (SE-HPLC) were found to be
      suitable techniques for this. It is concluded that all protein fractions migrate
      to the center of the cone as a result of which the composition of the gluten
      enriched fraction remains rather similar to that in the original flour. However,
      the larger glutenin polymer fraction migrated faster, as a result of which the
      concentration of large polymers was increased with a factor 2.4 compared to that
      of Soissons flour. The concentration of monomers in the gluten-enriched fraction
      was decreased to 70% of the original concentration in the original wheat flour.

PMID- 20825156
TI  - Recombinant expression of two bacteriophage proteins that lyse clostridium
      perfringens and share identical sequences in the C-terminal cell wall binding
      domain of the molecules but are dissimilar in their N-terminal active domains.
AB  - Clostridium perfringens is a Gram-positive anaerobic spore-forming bacterium
      capable of producing four major toxins that are responsible for disease symptoms
      and pathogenesis in a variety of animals, humans, and poultry. The organism is
      the third leading cause of human foodborne bacterial disease, and C. perfringens
      is the presumptive etiologic agent of necrotic enteritis among chickens, which in
      the acute form can cause increased mortality among broiler flocks. Countries that
      have complied with the ban on antimicrobial growth promoters (AGP) in feeds have
      had increased incidences of C. perfringens-associated necrotic enteritis in
      poultry. To address this issue, new antimicrobial agents, putative lysins from
      the genomes of bacteriophages, are identified. Two putative phage lysin genes
      (ply) from the clostridial phages phiCP39O and phiCP26F were cloned and expressed
      in Escherichia coli , and the resultant proteins were purified to near
      homogeneity. Gene and protein sequencing revealed that the predicted and
      chemically determined amino acid sequences of the two recombinant proteins were
      homologous to N-acetylmuramoyl-l-alanine amidases. The proteins were identical in
      the C-terminal putative cell-wall binding domain, but only 55% identical to each
      other in the presumptive N-terminal catalytic domain. Both recombinant lysins
      were capable of lysing both parental phage host strains of C. perfringens as well
      as other strains of the bacterium in spot and turbidity reduction assays. The
      observed reduction in turbidity was correlated with up to a 3 log cfu/mL
      reduction in viable C. perfringens on brain-heart infusion agar plates. However,
      other member species of the clostridia were resistant to the lytic activity by
      both assays.

PMID- 20825158
TI  - Production and migration of mycotoxins in sweet pepper analyzed by Multimycotoxin
      LC-MS/MS.
AB  - In this work the presence and migration behavior of mycotoxins formed in sweet
      pepper, inoculated by Fusarium species involved in internal fruit rot, were
      investigated. Two different commercial sweet pepper cultivars were inoculated
      with two different Fusarium proliferatum isolates that were sampled from diseased
      peppers. After 10 days of incubation at 20  degrees C in a closed container, the
      lesion caused by the fungal infection was dissected. Around the lesion, up to
      three concentric rings of pepper fruit tissue with a width of 5 mm were cut out
      and analyzed using a multimycotoxin LC-MS/MS method. The analyses resulted in the
      detection of beauvericin and fumonisins B(1), B(2), and B(3). Beauvericin was
      detected only in the lesions (95%), and the levels varied between 67 and 73800
      MUg/kg. Fumonisins B(1), B(2), and B(3) were detected in the lesions and in the
      surrounding tissue, indicating migration of these toxins into healthy parts of
      the sweet pepper. In the lesion the fumonisin B(1) level varied between 690 and
      104000 MUg/kg. Even in the outer ring fumonisin B(1) was still present. Mostly it
      was present at a lower level than in the lesion, with a maximum level of 556
      MUg/kg. A similar migration behavior was obtained for fumonisins B(2) and B(3),
      but lower levels were detected in the lesions, up to 10900 and 1287 MUg/kg,
      respectively. The analysis of 20 pepper samples resulted in the detection of
      beauvericin or alternariol. Seven samples were contaminated, and the level of
      beauvericin was 124 MUg/kg (N = 1), whereas the level of alternariol varied from
      below the LOQ (6.6 MUg/kg) to 101 MUg/kg (N = 6).

PMID- 20825159
TI  - A scanning tunneling microscope as a tunable nanoantenna for atomic scale control
      of optical-field enhancement.
AB  - The high stability of a low temperature (9 K) scanning tunneling microscope
      junction is used to precisely adjust the enhancement of an external pulsed vacuum
      ultraviolet (VUV) laser. The ensuing VUV optical-field strength is mapped on an
      hydrogenated Si(100) surface by imprinting locally one-photon atomic scale
      hydrogen desorption. Subsequent to irradiation, topography of the Si(100):H
      surface at the reacted area revealed a desorption spot with unprecedented atomic
      precision. Our results show that the shapes, positions, and sizes of the
      desorption spots are correlated to the calculated optical-field structure,
      offering real control of the optical-field distribution at molecular scale.

PMID- 20825160
TI  - Deterministic coupling of a single nitrogen vacancy center to a photonic crystal
      cavity.
AB  - We describe and experimentally demonstrate a technique for deterministic, large
      coupling between a photonic crystal (PC) nanocavity and single photon emitters.
      The technique is based on in situ scanning of a PC cavity over a sample and
      allows the precise positioning of the cavity over a desired emitter with
      nanoscale resolution. The power of the technique is demonstrated by coupling the
      PC nanocavity to a single nitrogen vacancy (NV) center in diamond, an emitter
      system that provides optically accessible electron and nuclear spin qubits.

PMID- 20825161
TI  - Comments on "Near-infrared hyperspectral unmixing based on a minimum volume
      criterion for fast and accurate chemometric characterization of counterfeit
      tablets".

PMID- 20825162
TI  - Effect of processing additive on the nanomorphology of a bulk heterojunction
      material.
AB  - The bulk heterojunction (BHJ) material Si-PDTBT:PC(70)BM is sensitive to the use
      of a small amount of 1-chloronaphthalene (CN) as a processing additive; CN as a
      cosolvent (e.g., 4% in chlorobenzene) causes in a factor of 2 increase in the
      power conversion efficiency of BHJ solar cells. The morphology of the BHJ
      material, prepared with and without the CN additive is studied with top-down
      transmission electron microscopy, cross-sectional transmission electron
      microscopy, and atomic force microscopy. The improved performance is the result
      of changes in the nanoscale morphology. Field-effect transistor measurements are
      consistent with the observed changes in morphology.

PMID- 20825164
TI  - Facile iterative synthesis of biphenyl dendrons with a functionalized focus.
AB  - An iterative procedure gives 1,3,5-phenyl-linked dendrons of up to the fourth
      generation and enables the formation of different generations of iridium(III)
      complex-cored dendrimers. The convergent synthesis uses N,N'-1,8-naphthyl-3,5
      dibromophenylboronamide as the key building block. The iterative synthesis cycle
      involves deprotection of the boronamide-focused dendron to form a boronic acid
      and subsequent Suzuki coupling either with the N,N'-1,8-naphthyl-3,5
      dibromophenylboronamide to give the next dendron generation or with an activated
      core to form a dendrimer.

PMID- 20825163
TI  - Tandem laser-induced fluorescence and mass spectrometry detection for high
      performance liquid chromatography analysis of the in vitro metabolism of
      doxorubicin.
AB  - Structural characterization, identification, and quantification of xenobiotics
      and their metabolic products commonly require the use of at least two different
      techniques. This has been the case in the analysis of metabolic products of
      doxorubicin, a widely used fluorescent anthracycline for the treatment of tumors
      and leukemia. In this work, we combine high-performance liquid chromatography
      (HPLC) with a tandem laser-induced fluorescence (LIF) and mass spectrometry (MS)
      detection scheme for the characterization of doxorubicin and its metabolites
      produced in the postmitochondrial fraction prepared from Fischer 344 rat liver.
      LIF detection allowed quantification of the metabolic compounds while MS
      detection aided in the identification of the metabolites. Using this HPLC-LIF-MS
      methodology, the disappearance of doxorubicin and the appearance of 7
      deoxydoxorubicinone and 7-deoxydoxorubicinolone were monitored over the course of
      40 min. This application demonstrates the potential of the tandem LIF-MS
      detection scheme in quantification and characterization of biotransformations of
      fluorescent xenobiotics of biomedical and environmental relevance. Furthermore,
      this detection scheme would be particularly relevant in the analysis of
      fluorescent analytes in complex samples and in validation of methods for the
      analysis of such samples that typically rely only on LIF detectors.

PMID- 20825165
TI  - Binding of beta-D-glucosides and beta-D-mannosides by rice and barley beta-D
      glycosidases with distinct substrate specificities.
AB  - Predominantly, rice Os3BGlu7 operates as a beta-d-glucosidase (EC 3.2.1.21),
      while barley HvBII acts as a beta-d-mannosidase (EC 3.2.1.25). Saturation
      transfer difference nuclear magnetic resonance (STD NMR) and transferred nuclear
      Overhauser effect (trNOE) spectroscopy in conjunction with quantum
      mechanics/molecular mechanics (QM/MM) modeling and docking at the 6-31+G* level
      were used to investigate binding of S- and O-linked gluco- and manno-configured
      aryl-beta-d-glycosides to Os3BGlu7 and HvBII. Kinetic analyses with 4-nitrophenyl
      beta-d-thioglucoside (4NP-S-Glc) and 4-nitrophenyl beta-d-thiomannoside (4NP-S
      Man) indicated that the inhibitions were competitive with apparent K(i) constants
      of 664 and 710 MUM for Os3BGlu7 and 95 and 266 MUM for HvBII, respectively. The
      STD NMR and trNOESY experiments revealed that 4NP-S-Glc and 4NP-S-Man bound
      weakly in (4)C(1) conformations to Os3BGlu7; 4NP-S-Glc adopted (3)S(5) (B(3,O))
      or (1)S(3) ((1,4)B) conformations, and 4NP-S-Man preferred (4)C(1) geometry, when
      bound to HvBII. The QM modeling and docking, based on GLIDE scores, predicted
      that 4NP-O-Glc, 4NP-O-Man, and 4NP-S-Man bound preferentially in (1)S(3)
      geometries to both enzymes, contrary to 4NP-S-Glc that could also adopt a (4)C(1)
      conformation, although in a "flipped-down" ring position. The experimental and
      computational data suggested that in glycoside recognition and substrate
      specificity of Os3BGlu7 and HvBII, a combination of the following determinants is
      likely to play key roles: (i) the inherent conformational and spatial
      flexibilities of gluco- and manno-configured substrates in the enzymes' active
      sites, (ii) the subtle differences in the spatial disposition of active site
      residues and their capacities to form interactions with specific groups of
      substrates, and (iii) the small variations in the charge distributions and shapes
      of the catalytic sites.

PMID- 20825166
TI  - Fluorescence enhancement, blinking suppression, and gray states of individual
      semiconductor nanocrystals close to gold nanoparticles.
AB  - The optical properties of nanocrystals are drastically changed by the interaction
      with adjacent metal nanoparticles. By time-resolved photoluminescence
      spectroscopy, we investigate CdSe multishell nanocrystals coupled to self
      assembled films of Au nanoparticles. The distance between emitter and metal is
      adjusted by coating the nanocrystals with silica shells. These NCs showed
      increased fluorescence intensity, a decreased fluorescence lifetime, strong
      blinking suppression, and fluorescence from gray states. These observations can
      be explained by the metal particle induced change of excitation and recombination
      rates.

PMID- 20825167
TI  - Transition-metal-free catalytic synthesis of 1,5-diaryl-1,2,3-triazoles.
AB  - 1,5-Diarylsubstituted 1,2,3-triazoles are formed in high yield from aryl azides
      and terminal alkynes in DMSO in the presence of catalytic tetraalkylammonium
      hydroxide. The reaction is experimentally simple, does not require a transition
      metal catalyst, and is not sensitive to atmospheric oxygen and moisture.

PMID- 20825169
TI  - Gas analysis by monitoring molecular diffusion in a microfluidic channel.
AB  - Despite the increasing industrial and domestic demand for gas analyzers, the
      unmanageable size and cost of the available devices prevent them from fulfilling
      this pervasive need. In this paper, we demonstrate that, monitored by a generic
      gas sensor, the progress rate of a gaseous analyte's free diffusion through an
      air-filled centimeter-long microfluidic channel yields sufficient information for
      gas recognition. The installation of additional channels made from different
      materials provides more uncorrelated information, enabling more detailed gas
      analyses. This device classifies gases based on their physical features at room
      temperature, namely, diffusivity and interaction (physisorption/desorption) with
      channel walls. This process does not degrade the gas discriminating element of
      the instrument. Our prototype, featuring a 50 mm long 50 MUm bore borosilicate
      glass channel, successfully differentiated between 24 analytes, including four
      butanol isomers, and estimated the compositions of their binary and ternary gas
      mixtures dispersed in air at different concentration levels. The findings
      presented here are directly applicable to the production of a new inexpensive,
      compact, portable, and durable generation of artificial olfaction system whose
      performance is almost entirely independent of the utilized gas sensor's drift.

PMID- 20825168
TI  - Iron-catalyzed heterocycle and arene deprotonative alkylation.
AB  - A method for iron-catalyzed deprotonative alkylation of arene C-H bonds by alkyl
      iodides and bromides has been developed. In the presence of an amide base, both
      primary and secondary alkyl halides can be coupled with furans, thiophenes,
      pyridine derivatives, and some electron-withdrawing-group containing arenes.

PMID- 20825170
TI  - Structure and mechanism of the 6-oxopurine nucleosidase from Trypanosoma brucei
      brucei.
AB  - Trypanosomes are purine-auxotrophic parasites that depend upon nucleoside
      hydrolase (NH) activity to salvage nitrogenous bases necessary for nucleic acid
      and cofactor synthesis. Nonspecific and purine-specific NHs have been widely
      studied, yet little is known about the 6-oxopurine-specific isozymes, although
      they are thought to play a primary role in the catabolism of exogenously derived
      nucleosides. Here, we report the first functional and structural characterization
      of the inosine-guanosine-specific NH from Trypanosoma brucei brucei. The enzyme
      shows near diffusion-limited efficiency coupled with a clear specificity for 6
      oxopurine nucleosides achieved through a catalytic selection of these substrates.
      Pre-steady-state kinetic analysis reveals ordered product release, and a rate
      limiting structural rearrangement that is associated with the release of the
      product, ribose. The crystal structure of this trypanosomal NH determined to 2.5
      A resolution reveals distinctive features compared to those of both purine- and
      pyrimidine-specific isozymes in the framework of the conserved and versatile NH
      fold. Nanomolar iminoribitol-based inhibitors identified in this study represent
      important lead compounds for the development of novel therapeutic strategies
      against trypanosomal diseases.

PMID- 20825171
TI  - Interfacial activity and interfacial shear rheology of native beta-lactoglobulin
      monomers and their heat-induced fibers.
AB  - Interfacial properties of native beta-lactoglobulin monomers and their heat
      induced fibers, of two different lengths, were investigated at pH 2, through
      surface tension measurements at water-air and water-oil interfaces and
      interfacial shear rheology at the water-oil interface. The applied heat treatment
      generates a mixed system of fibers with unconverted monomers and hydrolyzed
      peptides. The surface tension of this system at the water-air interface decreased
      more rapidly than the surface tension of native monomers, especially at short
      times (10(-3) to 10(2) s). This behavior was not observed when the unconverted
      monomers and peptides were removed by dialysis. At the water-oil interface, the
      adsorption kinetics was much faster than at the water-air interface, with a
      plateau interfacial pressure value reached after 1 h of adsorption. For all the
      systems, interfacial shear rheology showed the formation of a highly elastic
      interface, with solid-like behavior at 1-10(3) s time scales. The highest modulus
      was observed for the long fibers and the lowest for the native monomers. Creep
      compliance curves in the linear regime could be reduced to a single master curve,
      showing similar spectra of relaxation times for all investigated systems. Upon
      large deformations, the interfaces formed with long fibers showed the most rigid
      and fragile behavior. This rigidity was even more pronounced in the presence of
      unconverted monomers.

PMID- 20825172
TI  - Proteomic analysis of clonal interstitial aortic valve cells acquiring a pro
      calcific profile.
AB  - Calcific degeneration represents the most frequent aortic valve disease observed
      in industrialized countries. Our aim is to study modifications in the cytosolic
      and membrane protein profile of aortic interstitial valve cells (VIC) acquiring a
      pro-calcific phenotype. We studied a clonal population of bovine VIC that
      expresses bone-related proteins (such as alkaline phosphatase [ALP]) and
      calcifies a collagen matrix in response to endotoxin (LPS) treatment. A proteomic
      analysis was performed on proteins extracted from cells treated for 12 days with
      LPS (100 ng/mL) versus control. We identified 34 unique cytosolic and 10 unique
      membrane-associated proteins showing significant changes after treatment. These
      proteins are involved in several cellular functions, such as chaperone-mediated
      protein folding, protein metabolism and transport, cell redox/nitric oxide
      homeostasis, and cytoskeletal organization. Reduced expression of proteins
      involved in NOS bioactivity (such as DDAH-1 and -2) suggested a role for the l
      arginine/ADMA ratio in controlling VIC phenotypic profile. In accordance with
      this hypothesis, we observed that exposure of clonal cells to l-arginine
      prevented LPS-induced ALP expression and collagen calcification. In conclusion,
      we identified several proteins involved in structural, metabolic, and signaling
      functions that are significantly altered in aortic VIC acquiring a pro-calcific
      profile, thus giving new insights into the pathogenesis of aortic valve
      degeneration.

PMID- 20825173
TI  - Chemistry of hexafluorobicyclo[1.1.0]butane: a computational study.
AB  - Despite its very weak central C-C bond, the yet-unknown hexafluorobicyclobutane
      is predicted to be quite robust. Unlike the parent hydrocarbon, which undergoes
      thermal rearrangement to butadiene, the perfluoro compound will yield
      hexafluorocyclobutene upon heating. The fluorobicyclobutane will react under mild
      conditions with a variety of reagents, in particular with certain alkenes in a
      new type of concerted transformation. This "fluorohomoene" reaction is shown to
      be a pseudopericyclic process, as is condensation of the bicyclobutane with
      water. Whereas the carbene 3-butenylidene rearranges primarily to butadiene, its
      perfluoro counterpart is predicted to be an efficient precursor for
      hexafluorobicyclobutane.

PMID- 20825174
TI  - Experimental evidence of the occurrence of intramolecular electron transfer in
      catalyzed 1,2-dioxetane decomposition.
AB  - The activation parameters for the thermal decomposition of 13 acridinium
      substituted 1,2-dioxetanes, bearing an aromatic moiety, were determined and their
      chemiluminescence emission quantum yields estimated, utilizing in situ
      photosensitized 1,2-dioxetane generation and observation of its thermal
      decomposition kinetics, without isolation of these highly unstable cyclic
      peroxides. Decomposition rate constants show linear free-energy correlation for
      electron-withdrawing substituents, with a Hammett reaction constant of rho = 1.3
      +/- 0.1, indicating the occurrence of an intramolecular electron transfer from
      the acridinium moiety to the 1,2-dioxetane ring, as postulated by the
      intramolecular chemically initiated electron exchange luminescence (CIEEL)
      mechanism. Emission quantum yield behavior can also be rationalized on the basis
      of the intramolecular CIEEL mechanism, additionally evidencing its occurrence in
      this transformation. Both relations constitute the first experimental evidence
      for the occurrence of the postulated intramolecular electron transfer in the
      catalyzed and induced decomposition of properly substituted 1,2-dioxetanes.

PMID- 20825175
TI  - FRET-derived ratiometric fluorescent K+ sensors fabricated from thermoresponsive
      poly(N-isopropylacrylamide) microgels labeled with crown ether moieties.
AB  - We report on the fabrication of ratiometric fluorescent K(+) sensors based on
      thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) microgels covalently
      incorporated with K(+)-recognizing 4-acrylamidobenzo-18-crown-6 residues
      (B18C6Am), fluorescence resonance energy transfer (FRET) donor dyes, 4-(2
      acryloyloxyethylamino)-7-nitro-2,1,3-benzoxadiazole (NBDAE), and rhodamine-B
      based FRET acceptors (RhBEA) by utilizing K(+)-induced changes in microgel volume
      phase transition (VPT) temperatures. P(NIPAM-B18C6Am-NBDAE-RhBEA) microgels were
      synthesized via the free radical emulsion copolymerization technique. The spatial
      proximity between FRET pairs (NBDAE and RhBEA dyes) within microgels can be tuned
      via thermoinduced collapse and swelling of thermoresponsive microgels above and
      below VPT temperatures, leading to the facile modulation of FRET efficiencies.
      B18C6Am moieties within P(NIPAM-B18C6Am-NBDAE-RhBEA) microgels can preferentially
      capture K(+) via the formation of 1:1 molecular recognition complexes, resulting
      in the enhancement of microgel hydrophilicity and elevated VPT temperatures.
      Thus, the gradual addition of K(+) into microgel dispersions at intermediate
      temperatures, i.e., between VPT temperatures of P(NIPAM-B18C6Am-NBDAE-RhBEA)
      microgels in the absence and presence of K(+) ions, respectively, can directly
      lead to the reswelling of initially collapsed microgels. This process can be
      monitored by changes in fluorescence intensity ratios, i.e., FRET efficiencies.
      The presence of FRET pairs within P(NIPAM-B18C6Am-NBDAE-RhBEA) microgels allows
      for the facile in situ monitoring of thermoinduced and K(+)-induced VPTs of
      dually responsive microgels. The response time for fluorescent K(+)-sensing was
      further investigated via the stopped-flow technique, which reveals that the
      process completes within ~4 s. This work represents the first report of
      thermoresponsive microgel-based ratiometric fluorescent sensors for both K(+)
      ions and temperatures.

PMID- 20825176
TI  - Effect of large-amplitude alternating current modulation on apparent
      reversibility of electrode processes.
AB  - We examined the effect of a large-amplitude high-frequency alternating potential
      modulation on direct currents associated with irreversible, quasi-reversible, and
      reversible electron-transfer processes occurring at microelectrodes under
      voltammetric conditions. All irreversible processes appear to be accelerated by
      the superimposed ac modulation, and under certain conditions this may even lead
      to an electrochemical etching of noble metal electrodes. In the case of electrode
      processes which are reversible on the time scale of a dc polarization, but quasi
      reversible on the time scale of the ac modulation, the distortion of
      voltammograms caused by the ac modulation can provide useful information about
      the kinetics of fast electron-transfer processes. For completely reversible
      electrode processes the effect of the large-amplitude ac modulation is
      essentially trivial; the distortion of voltammetric curves causes broadening of
      analytical signals without providing any useful information.

PMID- 20825177
TI  - Polyhomologation. A living C1 polymerization.
AB  - The physical properties of synthetic macromolecules are strongly coupled to their
      molecular weight (MW), topology, and polydispersity index (PDI). Factors that
      contribute to their utility include the control of functionality at the
      macromolecule termini and copolymer composition. Conventional polymerization
      reactions that produce carbon backbone polymers (ionic, free radical, and
      coordination) provide little opportunity for controlling these variables. Living
      polymerizations, sometimes referred to as controlled polymerizations, have
      provided the means for achieving these goals. Not surprisingly, these reactions
      have had a profound impact on polymer and materials science. Three basic reaction
      types are used for the synthesis of most carbon backbone polymers. The first
      examples of "living" polymerizations were developed for ionic polymerizations
      (cationic and anionic). These reactions, which can be technically challenging to
      perform, can yield excellent control of molecular weight with very low
      polydispersity. The second reaction type, free radical polymerization, is one of
      the most widely used polymerizations for the commercial production of high
      molecular weight carbon backbone polymers. Nitroxide mediated polymerization
      (NMP), reversible addition-fragmentation chain transfer polymerization (RAFT),
      and atom transfer radical polymerization (ATRP) have emerged as three of the more
      successful approaches for controlling these reactions. The third type, transition
      metal mediated coordination polymerization, is the most important method for
      large-scale commercial polyolefin production. Simple nonfunctional hydrocarbon
      polymers such as polyethylene (PE), polypropylene, poly-alpha-olefins, and their
      copolymers are synthesized by high pressure-high temperature free radical
      polymerization, Ziegler-Natta or metallocene catalysts. Although these catalysts
      of exceptional efficiency that produce polymers on a huge scale are in common
      use, control that approaches a "living polymerization" is rare. Although the
      controlled synthesis of linear "polyethylene" described in this Account is not
      competitive with existing commercial processes for bulk polymer production, they
      can provide quantities of specialized materials for the study of structure
      property relationships. This information can guide the production of polymers for
      new commercial applications. We initiated a search for novel polymerization
      reactions that would produce simple hydrocarbon polymers with the potential for
      molecular weight and topological control. Our research focused on polymerization
      reactions that employ nonolefin monomers, more specifically the polymerization of
      ylides and diazoalkanes. In this reaction, the carbon backbone is built one
      carbon at a time (C1 polymerization). These studies draw upon earlier
      investigations of the Lewis acid catalyzed polymerization of diazoalkanes and
      build upon our discovery of the trialkylborane initiated living polymerization of
      dimethylsulfoxonium methylide 1.

PMID- 20825178
TI  - Interfacial partitioning tracer test measurements of organic-liquid/water
      interfacial areas: application to soils and the influence of surface roughness.
AB  - Interfacial areas between an organic immiscible liquid and water were measured
      for two natural soils using the aqueous-phase interfacial partitioning tracer
      test method. The measured values were compared to measured values for silica
      sands compiled from the literature. The data were compared using the maximum
      specific interfacial area as a system index, which is useful for cases wherein
      fluid saturations differ. The maximum specific interfacial areas measured for the
      soils were significantly larger than the values obtained for the sands. The
      disparity between the values was attributed to the impact of surface roughness on
      solid surface area and hence film-associated interfacial area. A good correlation
      was observed between maximum specific interfacial area and specific solid surface
      area measured with the N(2)/BET method. The correlation may serve as a means by
      which to estimate maximum specific organic-liquid/water interfacial areas.
      Interfacial areas measured with the interfacial partitioning tracer method were
      compared to interfacial areas measured with high-resolution microtomography.
      Values measured with the former method were consistently larger than those
      measured with the latter, consistent with the general inability of the
      microtomography method to characterize roughness-associated surface area.

PMID- 20825179
TI  - Microscopic and spectroscopic characterization of Hg(II) immobilization by
      mackinawite (FeS).
AB  - This study investigated the solid-phase Hg formed by reacting 0.005 or 0.01 M
      Hg(II) with 10 g/L mackinawite (FeS) as a function of pH in 0.2 M chloride
      solutions using X-ray diffraction (XRD), transmission electron microscopy (TEM),
      and extended X-ray absorption fine structure (EXAFS) analyses. Under all
      experimental conditions, XRD analysis showed formation of metacinnabar (beta-HgS)
      as a bulk-phase sorption product, in agreement with the results from high angle
      annular dark field-scanning transmission electron microscopy (HAADF-STEM) and
      selected area electron diffraction (SAED) in TEM analysis. HAADF-STEM and energy
      dispersive X-ray (EDX) analyses also suggested formation of Hg(II) surface
      precipitates. EXAFS analysis indicated that metacinnabar was the dominant product
      under most conditions, with Hg(II) chlorosulfide-like surface precipitates having
      increased contribution at lower Hg(II) concentration and higher pH. This finding
      is consistent with the results of desorption experiments using Hg(II)-complexing
      ligands. Considering the low solubility and high stability of metacinnabar, our
      results support the potential application of mackinawite for sequestering Hg(II)
      in anoxic environments.

PMID- 20825180
TI  - Incorporation of antifreeze proteins into polymer coatings using site-selective
      bioconjugation.
AB  - The diverse functional repertoire of proteins promises to yield new materials
      with unprecedented capabilities, so long as versatile chemical methods are
      available to introduce synthetic components at specific sites on biomolecule
      surfaces. As a demonstration of this potential, we have used site-selective
      strategies to attach antifreeze proteins found in Arctic fish and insects to
      polymer chains. This multivalent arrangement increases the thermal hysteresis
      activity of the proteins and leads to materials that can be cast into thin films.
      The polymer-protein conjugates retain the ability of the proteins to slow ice
      growth in subzero water and can inhibit ice formation after attachment to glass
      surfaces. These inexpensive materials may prove useful as coatings for device
      components that must function at low temperature without ice buildup. The polymer
      attachment also allows higher thermal hysteresis values to be achieved while
      using less protein, thus lowering the cost of these additives for biomedical
      applications.

PMID- 20825182
TI  - Chiral ice chromatography.
AB  - Water-ice particles simultaneously doped with beta-cyclodextrin and a salt
      enabled chromatographic separation of enantiomers without synthetic processes,
      and enhanced chiral recognition occurring in the liquid-water phase coexistent
      with the solid-ice phase.

PMID- 20825181
TI  - Structural comparisons of apo- and metalated three-stranded coiled coils clarify
      metal binding determinants in thiolate containing designed peptides.
AB  - Over the past two decades, designed metallopeptides have held the promise for
      understanding a variety of fundamental questions in metallobiochemistry; however,
      these dreams have not yet been realized because of a lack of structural data to
      elaborate the protein scaffolds before metal complexation and the resultant
      metalated structures which ultimately exist. This is because there are few
      reports of structural characterization of such systems either in their metalated
      or nonmetalated forms and no examples where an apo structure and the
      corresponding metalated peptide assembly have both been defined by X-ray
      crystallography. Herein we present X-ray structures of two de novo designed
      parallel three-stranded coiled coils (designed using the heptad repeat (a -> g))
      CSL9C (CS = Coil Ser) and CSL19C in their nonmetalated forms, determined to 1.36
      and 2.15 A resolutions, respectively. Leucines from either position 9 (a site) or
      19 (d site) are replaced by cysteine to generate the constructs CSL9C and CSL19C,
      respectively, yielding thiol-rich pockets at the hydrophobic interior of these
      peptides, suitable to bind heavy metals such as As(III), Hg(II), Cd(II), and
      Pb(II). We use these structures to understand the inherent structural differences
      between a and d sites to clarify the basis of the observed differential
      spectroscopic behavior of metal binding in these types of peptides. Cys side
      chains of (CSL9C)(3) show alternate conformations and are partially preorganized
      for metal binding, whereas cysteines in (CSL19C)(3) are present as a single
      conformer. Zn(II) ions, which do not coordinate or influence Cys residues at the
      designed metal sites but are essential for forming X-ray quality crystals, are
      bound to His and Glu residues at the crystal packing interfaces of both
      structures. These "apo" structures are used to clarify the changes in metal site
      organization between metalated As(CSL9C)(3) and to speculate on the differential
      basis of Hg(II) binding in a versus d peptides. Thus, for the first time, one can
      establish general rules for heavy metal binding to Cys-rich sites in designed
      proteins which may provide insight for understanding how heavy metals bind to
      metallochaperones or metalloregulatory proteins.

PMID- 20825183
TI  - Torsion potential in polydiacetylene: accurate computations on oligomers
      extrapolated to the polymer limit.
AB  - The optoelectronic properties of polydiacetylenes can be strongly modulated by
      torsions along the polymer chains. These as well as other distortions of the
      nominally coplanar polydiacetylene backbones result in the major color changes
      observed for these materials in response to a variety of external, low-energy
      stimuli; such color changes form the basis for the many applications of
      polydiacetylenes as sensor materials. There has been little theoretical work
      related to backbone distortions in polydiacetylenes; actually, previous estimates
      of the torsional barriers in these systems differ by an order of magnitude.
      Understanding the impact that polymer torsions have upon the properties of
      polydiacetylenes necessitates accurate estimates of the torsion potentials. Here,
      by using computationally efficient, wave-function-based electronic structure
      methods on increasingly larger oligomers, we present reliable estimates of the
      torsional barriers in model diacetylene oligomers and provide an accurate
      extrapolation of these values to the polymer limit.

PMID- 20825185
TI  - High-throughput screening of dendrimer-binding drugs.
AB  - A convenient approach for the high-throughput screening of dendrimer-binding
      drugs by NMR techniques including saturation transfer difference (STD) NMR and
      Hadamard-encoded nuclear Overhauser effect measurements is presented. The
      screening results for insoluble drugs show that phenylbutazone and
      sulfamethoxazole prefer to localize in the interior pockets of dendrimer, while
      mycophenolic acid mostly binds on the dendrimer surface, and noncharged insoluble
      drugs like trimethoprim and primidone do not interact with dendrimers. In another
      path for soluble drugs, n-butanoic acid and dimethylformamide are screened as
      dendrimer-binding compounds from a screening pool containing eight soluble
      compounds by STD NMR. The screening of dendrimer-binding insoluble or soluble
      compounds can be finished within an hour.

PMID- 20825184
TI  - The intramolecular charge transfer state in carbonyl-containing polyenes and
      carotenoids.
AB  - Numerous femtosecond time-resolved optical spectroscopic experiments have
      reported that the lifetime of the low-lying S(1) state of carbonyl-containing
      polyenes and carotenoids decreases with increasing solvent polarity. The effect
      becomes even more pronounced as the number of double bonds in the conjugated pi
      electron system decreases. The effect has been attributed to an intramolecular
      charge transfer (ICT) state coupled to S(1), but it is still not clear what the
      precise molecular nature of this state is, and how it is able to modulate the
      spectral and dynamic properties of polyenes and carotenoids. In this work, we
      examine the nature of the ICT state in three substituted polyenes: crocetindial,
      which contains two terminal, symmetrically substituted carbonyl groups in
      conjugation with the pi-electron system, 8,8'-diapocarotene-8'-ol-8-al, which has
      one terminal conjugated carbonyl group and one hydroxyl group, and 8,8'
      diapocarotene-8,8'-diol, which has two terminal, symmetrically positioned,
      hydroxyl groups but no carbonyls. Femtosecond time-resolved optical spectroscopic
      experiments on these molecules reveal that only the asymmetrically substituted
      8,8'-diapocarotene-8'-ol-8-al exhibits any substantial effect of solvent on the
      excited state spectra and dynamics. The data are interpreted using molecular
      orbital theory which shows that the ICT state develops via mixing of the low
      lying S(1) (2(1)A(g)-like) and S(2) (1(1)B(u)-like) excited singlet states to
      form a resultant state that preferentially evolves in polar solvent and exhibits
      a very large (~25 D) dipole moment. Molecular dynamics calculations demonstrate
      that the features of the ICT state are present in ~20 fs.

PMID- 20825186
TI  - Unusual, solvent viscosity-controlled tautomerism and photophysics: meso
      alkylated porphycenes.
AB  - Stationary and time-resolved studies of 9,10,19,20-tetramethylporphycene and
      9,10,19,20-tetra-n-propylporphycene in condensed phases reveal the coexistence of
      trans and cis tautomeric forms. Two cis configurations, cis-1 and cis-2, play a
      crucial role in understanding the excited-state deactivation and tautomer
      conversion dynamics. The trans-trans tautomerization, involving intramolecular
      transfer of two hydrogen atoms, is extremely rapid (k >= 10(13) s(-1)), both in
      the ground and lowest electronically excited states. The cis-1-trans conversion
      rate, even though the process is thermodynamically more favorable, is much slower
      and solvent-dependent. This is explained by the coupling of alkyl group rotation
      with the hydrogen motion. Excited-state deactivation is controlled by solvent
      viscosity: the S(1) depopulation rate decreases by more than 2 orders of
      magnitude when the chromophore is transferred from a low-viscosity solution to a
      polymer film. Such behavior confirms a model for excited state deactivation in
      porphycene, which postulates that a conical intersection exists along the single
      hydrogen transfer path leading from the trans to a high energy cis-2 tautomeric
      form. For this process, the tautomerization coordinate includes not only hydrogen
      translocation but also large-amplitude twisting of the two protonated pyrrole
      moieties attached to the opposite sides of the ethylene bridge.

PMID- 20825187
TI  - Nanostructured ceria-silver synthesized in a one-pot redox reaction catalyzes
      carbon oxidation.
AB  - We introduce a new concept for a nanomaterial in terms of both synthesis and
      properties. The nanomaterial, aggregates of ceria particles around central silver
      metal (CeO(2)-Ag), was fabricated by a one-pot selective redox reaction using
      cerium(III) and silver(I) autocatalyzed by silver metal without the need for
      surfactants or organic compounds. This unique nanostructure is suitable as a
      catalyst, in contrast to core-shell materials wherein the shell deactivates the
      catalyst metal. The material was developed to be intimately related to catalytic
      carbon oxidation.

PMID- 20825188
TI  - Conducting polymer electrodes printed on hydrogel.
AB  - We report herein the micropatterning of poly(3,4-ethylenedioxythiophene) (PEDOT)
      on a hydrogel, agarose, to provide a fully organic, moist, and flexible
      electrode. The PEDOT/agarose electrodes were prepared through two electrochemical
      processes: electropolymerization of PEDOT into the hydrogel and electrochemical
      actuation-assisted peeling. We also present a typical application of the
      PEDOT/agarose electrode to the cultivation of contractile myotubes.

PMID- 20825189
TI  - Pyridine activation via copper(I)-catalyzed annulation toward indolizines.
AB  - The copper(I)-catalyzed regioselective [3 + 2] cyclization of pyridines toward
      alkenyldiazoacetates leading to functionalized indolizine derivatives is
      reported. A broad range of pyridine derivatives (including quinoline and
      isoquinoline) is compatible with this cyclization reaction. The process
      represents the first successful example of metal-catalyzed cyclization of a pi
      deficient heterocyclic system with alkenyldiazo compounds.

PMID- 20825191
TI  - Straightforward synthesis of deuterated precursors to demonstrate the biogenesis
      of aromatic thiols in wine.
AB  - Straightforward synthesis of labeled S-3-(hexan-1-ol)-glutathione and S-4-(4
      methylpentan-2-one)-glutathione has been developed through a conjugate addition
      optimization study. Sauvignon blanc fermentation experiments with the [(2)H(10)]
      S-4-(4-methylpentan-2-one)-glutathione used as a tracer released the
      corresponding deuterated thiol, thus proving the direct relationship with the 4
      mercapto-4-methylpentan-2-one under enological conditions. The conversion yield
      of such transformation was estimated to be close to 0.3%, opening an avenue for
      additional study on varietal thiol biogenesis.

PMID- 20825190
TI  - Molecular behavior of DNA origami in higher-order self-assembly.
AB  - DNA-based self-assembly is a unique method for achieving higher-order molecular
      architectures made possible by the fact that DNA is a programmable information
      coding polymer. In the past decade, two main types of DNA nanostructures have
      been developed: branch-shaped DNA tiles with small dimensions (commonly up to ~20
      nm) and DNA origami tiles with larger dimensions (up to ~100 nm). Here we aimed
      to determine the important factors involved in the assembly of DNA origami
      superstructures. We constructed a new series of rectangular-shaped DNA origami
      tiles in which parallel DNA helices are arranged in a zigzag pattern when viewed
      along the DNA helical axis, a design conceived in order to relax an intrinsic
      global twist found in the original planar, rectangular origami tiles. Self
      associating zigzag tiles were found to form linear arrays in both diagonal
      directions, while planar tiles showed significant growth in only one direction.
      Although the series of zigzag tiles were designed to promote two-dimensional
      array formation, one-dimensional linear arrays and tubular structures were
      observed instead. We discovered that the dimensional aspect ratio of the origami
      unit tiles and intertile connection design play important roles in determining
      the final products, as revealed by atomic force microscopy imaging. This study
      provides insight into the formation of higher-order structures from self
      assembling DNA origami tiles, revealing their unique behavior in comparison with
      conventional DNA tiles having smaller dimensions.

PMID- 20825192
TI  - Characterization of phenolic composition in Lamiaceae spices by LC-ESI-MS/MS.
AB  - A total of 38 phenolic compounds in the solid/liquid extracts of five Lamiaceae
      spices, rosemary, oregano, sage, basil, and thyme, were identified in the present
      study using LC-ESI-MS/MS. These compounds were distributed in four major
      categories, namely, hydroxycinnamic acid derivatives, hydroxybenzoic acid
      derivatives, flavonoids, and phenolic terpenes. Among them, the category of
      flavonoids was the largest, with 17 compounds. Identification of the phenolic
      compounds was carried out by comparing retention times and mass spectra with
      those of authentic standards. If standards were unavailable, phenolic compounds
      were identified on the basis of accurate mass of pseudomolecular [M - H](-) ions
      and tandem mass spectrometry (MS/MS) data. The results of accurate mass
      measurements fit well with the elemental composition of the compounds. The
      diagnostic fragmentation patterns of the compounds during collision-induced
      dissociation (CID) elucidated the structural information of the compounds
      analyzed.

PMID- 20825193
TI  - Dopant-induced shape evolution of colloidal nanocrystals: the case of zinc oxide.
AB  - The electrical, optical and other important properties of colloidal nanocrystals
      are determined mainly by the crystals' chemical composition, size and shape. The
      introduction of specific dopants is a general approach of modifying the
      properties of such nanocrystals in well-controlled ways. Here we show that in
      addition to altering the atomic composition of the nanocrystals the introduction
      of specific dopants can also lead to dramatic changes in morphology. The creation
      of Mg-doped ZnO nanocrystals provides an excellent example of this procedure;
      depending on the molar ratio of dopant precursor in the reagents, doped
      nanocrystals with well-defined shapes, from tetrapods to ultrathin nanowires,
      which exhibit tunable optoelectronic properties, are obtained for the first time.
      We find that the Mg dopants play an important role in the primary growth stage,
      resulting in initial growth seeds having diverse crystallographic structures,
      which are critical for the generation of doped nanocrystals with different
      shapes. We demonstrate that this "greener" synthetic scheme can be extended to
      other dopant systems and provides an attractive and effective strategy for
      fabricating doped ZnO nanocrystals with interesting compositional and spatial
      complexity.

PMID- 20825194
TI  - Modification of surface wettability through adsorption of partly fluorinated
      statistical and block polyelectrolytes from aqueous medium.
AB  - The wetting properties of electrostatically charged hydrophilic substrates were
      modified through adsorption of ultrathin layer of amphiphilic block or
      statistical polyelectrolyte from aqueous medium. The studied polymers were
      copolymers of 2-(dimethylamino)ethyl methacrylate (DMAEMA) and 2,2,2
      trifluoroethyl methacrylate (TFEMA). They were adsorbed on mica from varying pH
      conditions, either as dissolved unimers or as kinetically trapped aqueous
      nanoparticles. The structures (by atomic force microscopy) and wetting properties
      (by dynamic contact angle measurements) of the obtained surface layers were
      determined. The majority of the surface layers consisted of polymeric
      nanoparticles with varying surface coverage. Annealing at 150  degrees C
      flattened and spread the particles on the surfaces. The surface wettability was
      found to be significantly influenced by the morphology and chemical composition
      of the obtained polymeric surface layer. The surfaces with the most homogeneous
      and smooth polymer layers exhibited the lowest contact angle hysteresis. The
      advancing/receding contact angles on the most hydrophilic copolymer layer on mica
      were 47 degrees /<20 degrees , and on the least hydrophilic layer they were 96
      degrees /63 degrees . On unmodified mica surface the water contact angle is ~0
      degrees . When those copolymers that provided the highest contact angles on mica
      were adsorbed on cellulose fiber substrates and annealed at 120  degrees C,
      highly hydrophobic surfaces were obtained, with advancing contact angles around
      160 degrees .

PMID- 20825195
TI  - Mapping of selenium metabolic pathway in yeast by liquid chromatography-Orbitrap
      mass spectrometry.
AB  - A high-resolution mass spectrometric detection method is described for the
      identification of key metabolites in the selenium pathway in selenium enriched
      yeast. Iodoacetic acid (IAA) was used as the derivatizing reagent to stabilize
      the selenols. Oxidized forms of selenocysteine (Se-Cys), selenohomocystine (Se
      HCys), selenoglutathione (Se-GSH), seleno-gamma-glutamyl-cysteine (Se-Glu-Cys), N
      (2,3-dihydroxy-1-oxopropyl)-selenocysteine (Se-DOP-Cys), N-(2,3-dihydroxy-1
      oxopropyl)-selenohomocysteine (Se-DOP-HCys), selenomethionine (SeMet), seleno-S
      adenosyl-homocysteine (Se-AdoHcy), the conjugate of glutathione and N-(2,3
      dihydroxy-1-oxopropyl)-selenocysteine (GSH-Se-DOP-Cys), and the conjugate of
      glutathione and N-(2,3-dihydroxy-1-oxopropyl)-selenohomocysteine (GSH-Se-DOP
      HCys) were found in the selenium enriched yeast certified reference material
      (SELM-1). Selenols were also derivatized with a mercury tag, p
      hydroxymercurybenzoate (PHMB). The selenol-PHMB complexes showed the overlapped
      isotopic patterns of selenium and mercury, which provided supporting information
      for the identification of selenols. Both methods showed good agreement (<4 ppm
      difference) between the theoretical masses of the target compounds and the
      measured masses in the yeast matrix. The method using IAA as the derivatizing
      reagent was used to study the response of Saccharomyces cerevisiae to three forms
      of selenium, Se-Met, Na(2)SeO(3) (Se(IV)), and Na(2)SeO(4).10H(2)O (Se(VI))
      (concentration of Se: 100 mg/L). The production of selenocompounds observed over
      a 6 h period was high in the Se-Met treated group compared to the groups treated
      with Se(IV) and Se(VI).

PMID- 20825197
TI  - Structural and functional characterization of the recombinant human mitochondrial
      trifunctional protein.
AB  - The alpha and beta subunits of the human mitochondrial trifunctional protein
      (TFP), the multienzyme complex involved in fatty acid beta-oxidation, were
      coexpressed in Escherichia coli and purified to homogeneity by nickel affinity
      chromatography. The resulting alpha/His-beta construct was analyzed by gel
      filtration, sedimentation velocity, and electron microscopy, indicating a
      predominance of alpha(2)beta(2) and alpha(4)beta(4) complexes, with higher order
      oligomers. Electron microscopy indicated that the elementary species
      alpha(2)beta(2) had overall structural similarity with its bacterial homologue.
      As shown by cosedimentation and surface plasmon resonance analyses, recombinant
      TFP interacted strongly with cardiolipin and phosphatidylcholine, suggesting that
      the natural complex associates with the inner mitochondrial membrane through
      direct interactions with phospholipids. Recombinant TFP displayed 2-enoyl-CoA
      hydratase (ECH), l-3-hydroxyacyl-CoA dehydrogenase (HACD), and 3-ketoacyl-CoA
      thiolase (KACT) activities, and ECH and HACD each reached equilibrium when the
      downstream enzymes (HACD and KACT, respectively) were made inactive, indicating
      feed-back inhibition. The KACT activity was optimal at pH 9.5, sensitive to ionic
      strength, and inhibited at concentrations of its substrate 3-ketohexadecanoyl-CoA
      >5 MUM. Its kinetic constants (k(cat) = 169 s(-1), K(m) = 4 MUM) were consistent
      with those determined previously on a purified porcine TFP preparation. Using
      different assays, trimetazidine, an efficient antiaginal agent, had no
      significant inhibitory effect on any of the three enzymatic activities of the
      recombinant TFP preparation, in contrast with other reports. This study provides
      the first detailed structural and functional characterization of a recombinant
      human TFP preparation and opens the way to in-depth analyses through site
      directed mutagenesis.

PMID- 20825198
TI  - Practical multi-component synthesis of di- or tri-aryl (Heteraryl) substituted 2
      (pyridin-2-yl)imidazoles from simple building blocks.
AB  - A convenient and highly efficient multicomponent protocol has been developed for
      the synthesis of various poly-substituted 2-(pyridin-2-yl)imidazoles from 2
      cyanopyridine, corresponding aromatic aldehydes, and NH(4)OAc/primary amine.
      Notably, tri-substituted 2-(pyridin-2-yl)imidazoles were highly yielded when
      aromatic primary amines were used as substrates, but both di- and tri-substituted
      2-(pyridin-2-yl)imidazoles were obtained in one pot when some aliphatic primary
      amines were used as substrates.

PMID- 20825199
TI  - Reactive adsorption of ammonia on Cu-based MOF/graphene composites.
AB  - New composites based on HKUST-1 and graphene layers are tested for ammonia
      adsorption at room temperature in both dry and moist conditions. The materials
      are characterized by X-ray diffraction, FT-IR spectroscopy, adsorption of
      nitrogen, and thermal analyses. Unlike other MOF/GO composites reported in
      previous studies, these materials are water-stable. Ammonia adsorption capacities
      on the composites are higher than the ones calculated for the physical mixture of
      components, suggesting the presence of a synergetic effect between the MOF and
      graphene layers. The increased porosity and dispersive forces being the
      consequence of the presence of graphene layers are responsible for the enhanced
      adsorption. In addition to its retention via physical forces, ammonia is also
      adsorbed via binding to the copper sites in HKUST-1 and then, progressively, via
      reaction with the MOF component. This reactive adsorption is visible through two
      successive changes of the adsorbents' color during the breakthrough tests. More
      ammonia is adsorbed in moist conditions than in dry conditions owing to its
      dissolution in a water film present in the pore system.

PMID- 20825200
TI  - Solid-state nuclear magnetic resonance studies of vinyl polymer/silica colloidal
      nanocomposite particles.
AB  - Solid-state nuclear magnetic resonance (NMR) has been used to characterize the
      interface between the organic and inorganic components of "core-shell" colloidal
      nanocomposite particles synthesized by in situ aqueous (co)polymerization of
      styrene and/or n-butyl acrylate in the presence of a glycerol-functionalized
      silica sol. Polymer protons are in close proximity (<5 A) to surface silanol
      sites in all the nanocomposites studied, indicating that either styrene or n
      butyl side groups extend between the glycerol-functional silane molecules toward
      the surface of the silica particles. For the poly(styrene-co-n-butyl
      acrylate)/silica nanocomposite n-butyl acrylate residues are located closer to
      the surface of the silica particle than styrene residues, suggesting a specific
      interaction between the former and the glycerol-functionalized silica surface.
      The most likely explanation is a hydrogen bond between the ester carbonyl and the
      glycerol groups, although this cannot be observed directly. For the Bindzil CC40
      glycerol-functionalized silica sol the relative intensities of (29)Si NMR lines
      corresponding to T and Q(3) environments imply that there are approximately twice
      as many unreacted silanol groups on the silica surface as attached silane
      molecules.

PMID- 20825201
TI  - Interaction of n-octyl beta,D-glucopyranoside with giant magnetic-fluid-loaded
      phosphatidylcholine vesicles: direct visualization of membrane curvature
      fluctuations as a function of surfactant partitioning between water and lipid
      bilayer.
AB  - The present study deals with the morphological modifications of giant dioleoyl
      phosphatidylcholine vesicles (DOPC GUVs) induced by the nonionic surfactant n
      octyl beta,D-glucopyranoside at sublytic levels, i.e., in the first steps of the
      vesicle-to-micelle transition process, when surfactant inserts into the vesicle
      bilayer without disruption. Experimental conditions were perfected to exactly
      control the surfactant bilayer composition of the vesicles, in line with former
      work focused on the mechanical properties of the membrane of magnetic-fluid
      loaded DOPC GUVs submitted to a magnetic field. The purpose here was to
      systematically examine, in the absence of any external mechanical constraint, the
      dynamics of giant vesicle shape and membrane deformations as a function of
      surfactant partitioning between the aqueous phase and the lipid membrane,
      beforehand established by turbidity measurements from small unilamellar vesicles.

PMID- 20825202
TI  - ZnO nanoparticles immobilized on flaky layered double hydroxides as
      photocatalysts with enhanced adsorptivity for removal of acid red G.
AB  - Flaky layered double hydroxides (FLDH) composed of cross-linked nanoflakes were
      prepared by the reconstruction of their oxides in alkali solution. The effect of
      reconstruction temperatures on the physicochemical properties was investigated.
      FLDH with a specific surface area of as high as 217 m(2)/g was obtained at a
      reconstruction temperature of 6  degrees C, and its derived flaky mixed metal
      oxides (FMMO) had a specific surface area of 249 m(2)/g. The ZnO nanoparticles
      were homogeneously deposited on the surface of the FLDH by coprecipitation. After
      calcination at 500  degrees C for 2 h, the ZnO-coated FLDH was transformed into
      ZnO-coated flaky mixed metal oxides (FMMO). The powders were characterized by X
      ray diffraction, field-emission scanning electron microscopy, transmission
      electron microscope, N(2) adsorption-desorption isotherm, UV-vis diffuse
      reflectance spectroscopy, and Fourier transform infrared spectroscopy. In the
      presence of FLDH as a support, the ZnO nanoparticles were of about 10 nm in size
      and showed higher photocatalytic decomposition of acid red G than bare ZnO powder
      prepared under similar experimental conditions. It should be noted that the ZnO
      coated FMMO combined excellent adsorption with photocatalytic activity. The flaky
      structure of mixed metal oxides appears to play important roles in the adsorption
      and photodecomposition process.

PMID- 20825203
TI  - Chemistry of the oxophosphinidene ligand. 1. Electronic structure of the anionic
      complexes [MCp{P(O)R*}(CO)(2)](-) (M = Mo, W; R* = 2,4,6-C(6)H(2)(t)Bu(3)) and
      their reactions with H(+) and C-based electrophiles.
AB  - The anionic phosphide-bridged complexes (H-DBU)[M(2)Cp(2)(MU-PHR*)(CO)(4)] (M =
      Mo, W; R* = 2,4,6-C(6)H(2)(t)Bu(3); Cp = eta(5)-C(5)H(5), DBU = 1,8-diazabicyclo
      [5.4.0] undec-7-ene) react with molecular oxygen to give the corresponding
      oxophosphinidene complexes (H-DBU)[MCp{P(O)R*}(CO)(2)] as major products (Mo-P =
      2.239(1) A for the Mo complex). The latter anionic complexes are protonated by
      HBF(4).OEt(2) to give the hydroxyphosphide derivatives [MCp{P(OH)R*}(CO)(2)]. In
      the presence of excess acid, the molybdenum complex yields the fluorophosphide
      complex [MoCp(PFR*)(CO)(2)] (Mo-P = 2.204(1) A), while the tungsten compound
      reacts with excess HCl to give an unstable chlorophosphine complex
      [WCpCl(PHClR*)(CO)(2)] which is rapidly hydrolyzed to give
      [WCpCl{PH(OH)R*}(CO)(2)], having a complexed arylphosphinous acid (Mo-P =
      2.460(2) A). The molybdenum anion reacts with strong C-based electrophiles such
      as [Me(3)O]BF(4), Et(2)SO(4), C(2)H(3)C(O)Cl, and PhC(O)Cl to give the
      corresponding alkoxyphosphide derivatives [MoCp{P(OR)R*}(CO)(2)] (R = Me, Et,
      COC(2)H(3), COPh; Mo-P = 2.197(2) A for the benzoyl compound), as a result of the
      attack of the electrophile at the O atom of the oxophosphinidene ligand. In
      contrast, the reactions with milder alkylating reagents such as the alkyl halides
      MeI, EtI, C(3)H(5)Br, and C(3)H(3)Br give selectively the corresponding kappa(2)
      phosphinite complexes [MoCp{kappa(2)-OP(R)R*}(CO)(2)] [R = Me, Et, C(3)H(5),
      C(3)H(3); Mo-P = 2.3733(5) A for the allyl compound] as a result of the attack of
      the electrophile at the P atom of the oxophosphinidene ligand. According to
      density functional theory (DFT) calculations, the oxygen atom of the
      phosphinidene ligand bears the highest negative charge in the molybdenum anion,
      while the highest occupied molecular orbital (HOMO) of this complex has
      substantial Mo-P pi bonding character. Thus, it is concluded that the phosphinite
      complexes are formed under conditions of orbital control, while charge-controlled
      reactions tend to give alkoxyphosphide derivatives.

PMID- 20825204
TI  - Geometry effect on the strain-induced self-rolling of semiconductor membranes.
AB  - Semiconductor micro- and nanotubes can be formed by strain-induced self-rolling
      of membranes. The effect of geometrical dimensions on the self-rolling behavior
      of epitaxial mismatch-strained In(x)Ga(1-x)As-GaAs membranes are systematically
      studied both experimentally and theoretically using the finite element method.
      The final rolling direction depends on the length and width of the membrane as
      well as the diameter of the rolled-up tube. The energetics of the final states,
      the history of rolling process, and the kinetic control of the etching anisotropy
      ultimately determine the rolling behavior. Results reported here provide critical
      information for precise positioning and uniform large area assembly of
      semiconducting micro- and nanotubes for applications in photonics,
      microelectromechanical systems, etc.

PMID- 20825205
TI  - An aminolytic approach toward hierarchical beta-Ni(OH)(2) nanoporous
      architectures: a bimodal forum for photocatalytic and surface-enhanced raman
      scattering activity.
AB  - A surfactantless, trouble-free, and gentle wet chemistry approach has been used
      to interpret the precisely controlled growth of beta-Ni(OH)(2) with the
      assistance of ammonia and nickel acetate from seedless mild hydrothermal
      conditions. A thorough investigation of the reaction kinetics and product
      morphology with varied concentration of NH(3) and different reaction times
      suggests that a putative mechanism of dissolution, recrystallization, and
      oriented attachment supports the intelligent self-assembly of nanobuilding
      blocks. Associated characterizations (FTIR, PXRD, FESEM, EDAX, HRTEM, and Raman)
      have identified it to be pure beta-Ni(OH)(2) without any signature of
      contamination. The assembled units result in porous frameworks (nanoflowers and
      nanocolumns) and are indeed full of communally intersecting nanopetals/nanoplates
      with both lengths and widths on the order of micrometer to nanometer length
      scale. The as-synthesized material could also be used as a precursor for
      nanometric black NiO under calcination. The hydroxide has been found to be a
      potent and environmentally benign material because it warrants its photocatalytic
      activity through dye mineralization. Finally, Ni(OH)(2) has been photochemically
      derivatized with dosages of silver nanoparticles bringing a competent composite
      authority Ag@Ni(OH)(2), to give a full-proof enhanced field effect of prolific
      SERS activity. In a nutshell, these results are encouraging and fetch new promise
      for the fabrication of a low-cost and high-yielding greener synthetic protocol
      for a functional material with promising practicability.

PMID- 20825207
TI  - Methodology for inkjet printing of partially wetting films.
AB  - Inkjet printing of precisely defined structures is critical for the realization
      of a range of printed electronics applications. We develop and demonstrate a
      methodology to optimize the inkjet printing of two-dimensional, partially wetting
      films. When printed inks have a positive retreating contact angle, we show that
      any fixed spacing is ineffective for printing two-dimensional features. With
      fixed spacing, the bead contact angle begins large, leading to a bulging overflow
      of its intended footprint. Each additional line reduces the bead contact angle,
      eventually leading to separation of the bead. We propose a printing scheme that
      adjusts the line-to-line spacing to maintain a bead's contact angle between its
      advancing and retreating values as it is printed. Implementing this approach
      requires an understanding of the two-dimensional bead surface and compensation
      for evaporation during the print. We derive an analytic equation for the bead's
      surface with pinned contact lines and use an empirical fit for mass loss due to
      evaporation. Finally, we demonstrate that enhanced contact angle hysteresis,
      achieved by preprinting a feature's border, leads to better corner definition.

PMID- 20825206
TI  - Cylindrocyclophanes with proteasome inhibitory activity from the Cyanobacterium
      Nostoc sp.
AB  - Material collected from a parkway in the city of Chicago afforded the isolation
      of a Nostoc species (UIC 10022A). The extract of this strain displayed
      significant inhibition of the 20S proteasome as well as antiproliferative
      activity against HT29, MCF7, NCI-H460, and SF268 cancer cell lines. A
      standardized dereplication protocol allowed for the rapid identification of three
      known (11-13) and nine new (1-9) chlorinated cylindrocyclophanes from less than
      100 mg of organic extract. Scale-up isolation of 1-9 and 11-13 from a larger
      extract was guided by LC-UV-MS data. In addition, KBr enrichment of the culture
      media afforded the isolation of a brominated cylindrocyclophane (10). Biological
      evaluation of 1-5, 9, and 10-13 revealed a large range of activity against the
      20S proteasome and allowed the determination of preliminary structure-activity
      relationships of the cylindrocyclophane pharmacophore.

PMID- 20825208
TI  - Small-amplitude backbone motions of the spin-labeled lipopeptide trichogin GA IV
      in a lipid membrane as revealed by electron spin echo.
AB  - Trichogin GA IV is a lipopeptide antibiotic of fungal origin, which is known to
      be able to modify the membrane permeability. TOAC nitroxide spin-labeled
      analogues of this membrane active peptide were investigated in hydrated bilayers
      of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) by electron spin echo
      (ESE) spectroscopy. Because the TOAC nitroxide spin label is rigidly attached to
      the peptide backbone, it may report on the backbone orientational dynamics. The
      ESE signal in this system is observed below ~150 K. Previously, three-pulse
      stimulated ESE was found to be sensitive to two types of orientational motion of
      spin-labeled POPC lipid bilayers at these temperatures. The first type is fast
      stochastic librations, with a correlation time on the nanosecond scale (which
      also manifests itself in a two-pulse primary ESE experiment). The second type is
      slow millisecond inertial rotations. In the present work, we find that at low
      molar peptide to lipid ratio (1:200), where the individual peptide molecules are
      randomly distributed at the membrane surface, the spin labels show only a fast
      type of motion. At the high molar peptide to lipid ratio (1:20), a slow motion is
      also observed. Because at this high concentration trichogin GA IV is known to
      change its orientation from the in-plane topology to the transmembrane
      disposition, the observed onset of a slow motion may be safely attributed to the
      dynamics of peptides, which are elongated along the lipid molecules of the
      membrane. The possible interrelation between this backbone rotational motion of
      the peptide antibiotic and the membrane leakage is discussed.

PMID- 20825209
TI  - Synthetic inositol phosphoglycans related to GPI lack insulin-mimetic activity.
AB  - Insulin signaling has been suggested, at least in part, to be affected by an
      insulin-mimetic species of low molecular weight. These inositol phosphoglycans
      (IPGs) are generated upon growth hormone/cytokine stimulation and control the
      activity of a multitude of insulin effector enzymes. The minimal structural
      requirements of IPGs for insulin-mimetic action have been debated. Two types of
      IPGs were suggested, and the IPG-A type resembles the core glycan of
      glycosylphosphatidylinositol (GPI)-anchors. In fact, purified GPI-anchors of
      lower eukaryotic origin have been shown to influence glucose homeostasis. To
      elucidate active IPGs, a collection of synthetic IPGs designed on the basis of
      previous reports of activity were tested for their insulin-mimetic activity. In
      vitro and ex vivo assays in rodent adipose tissue as well as in vivo analyses in
      mice were employed to test the synthetic IPGs. None of the IPGs we tested mimic
      insulin actions as determined by PKB/Akt phosphorylation and quantification of
      glucose transport and lipogenesis. Furthermore, none of the IPGs had any effect
      in in vivo insulin tolerance assays. In stark contrast to previous claims, we
      conclude that neither of the compounds tested is insulin-mimetic.

PMID- 20825210
TI  - Gold(I)-catalyzed cyclization of beta-allenylhydrazones: an efficient synthesis
      of multisubstituted N-aminopyrroles.
AB  - The gold(I)-catalyzed cycloisomerization of beta-allenylhydrazones provides an
      efficient access to multisubstituted N-aminopyrroles, which are obtained in good
      to excellent yields. This new intramolecular cyclization method can be applied
      either to alkyl- or aryl-substituted allenes. The reaction proceeds under mild
      conditions with short reaction times through a selective intramolecular 1,2-alkyl
      or -aryl migration extending the general scope of the reaction.

PMID- 20825211
TI  - An iSAFT density functional theory for associating polyatomic molecules.
AB  - The inhomogeneous statistical associating fluid theory (iSAFT) is extended to
      associating polyatomic molecular systems, using the inhomogeneous form of the
      association functional. The approach provides an accurate method for modeling a
      wide range of complex associating polyatomic systems, capable of investigating
      the full range of association for any bonding scheme. Theoretical results
      demonstrate the ability of the theory to model problems near surfaces and in the
      bulk over a wide range of conditions. The examples chosen in this paper elucidate
      the importance of such a theory, highlighting how reversible bonding governs the
      structure of a fluid near a surface and in confined environments, the molecular
      connectivity (formation of supramolecules, star polymers, etc.), and the phase
      behavior of the system (including reentrant order-disorder phase transitions).

PMID- 20825212
TI  - Microrheology and characteristic lengths in wormlike micelles made of a
      zwitterionic surfactant and SDS in brine.
AB  - We study the Brownian motion of probe particles embedded in a wormlike micellar
      fluid made of a zwitterionic surfactant N-tetradecyl-N,N-dimethyl-3-ammonio-1
      propanesulfonate (TDPS), sodium dodecyl sulfate (SDS), and salty water to get
      structural and dynamical information of the micellar network. The motion of the
      probe particles was tracked with diffusing wave spectroscopy, and the mean square
      displacement as a function of time for the particles was obtained. This allowed
      us to obtain the long-time diffusion coefficient for microspheres moving in the
      micellar network and the cage size where each particle is harmonically bound at
      short times in that network. The bulk mechanical susceptibility of the fluid
      determines the response of the probe particles excited by the thermal stochastic
      forces. As a consequence, the mean square displacement curves allowed us to
      calculate the elastic (storage) and the viscous (loss) moduli as a function of
      the frequency. From these curves, spanning a wide frequency range, we estimated
      the characteristic lengths as the mesh size, the entanglement length, the
      persistence length, and the contour length for micellar solutions of different
      zwitterionic surfactant concentration, surfactant ratio ([SDS]/[TDPS]), salt
      concentration, and temperature. Mesh size, entanglement length, and persistence
      length are almost insensitive to the change of these variables. In contrast, the
      contour length changes in an important way. The contour length becomes shorter as
      the temperature increases, and it presents a peak at a surfactant ratio of ~0.50
      0.55. When salt is added to the solution, the contour length presents a peak at a
      salt concentration of ~0.225 M, and in some solutions, this length can reach
      values of ~12 MUm. Scission energies help us to understand why the contour length
      first increases and then decreases when salt is added.

PMID- 20825213
TI  - QM/MM dynamics of CH3COO(-)-water hydrogen bonds in aqueous solution.
AB  - Two combined QM/MM molecular dynamics (MD) simulations, namely, HF/MM and
      B3LYP/MM, in which the central CH(3)COO(-) and its surrounding water molecules
      were treated at HF and B3LYP levels of accuracy, respectively, using the DZV+
      basis set, have been performed to investigate the characteristics of CH(3)COO(-)
      water hydrogen bonds in dilute aqueous solution. Both HF/MM and B3LYP/MM
      simulations clearly indicate relatively strong hydrogen bonds between CH(3)COO(-)
      oxygens and their nearest-neighbor waters compared with those of water-water
      hydrogen bonds in the bulk. In addition, it is observed that first-shell waters
      are either "loosely" or "tightly" bound to their respective CH(3)COO(-) oxygen
      atoms, leading to large fluctuations in the coordination number, ranging from 2
      to 5, with the prevalent value of 3. Among the HF and B3LYP methods for the
      description of the QM-treated region, the latter predicts slightly higher
      hydrogen-bond strength in the CH(3)COO(-)-water complex.

PMID- 20825214
TI  - Simulation of micelle formation in the presence of solutes.
AB  - We investigate solute encapsulation by copolymer micelles by performing
      discontinuous molecular dynamics simulations on a model solute-copolymer-solvent
      system. In this paper, we detail the effect of system density, copolymer mole
      fraction, and hydrophobic interaction between copolymer head and solute on the
      encapsulation efficiency and phase behavior of the system. The relative
      hydrophobicity of solute and copolymer head units acts as a coupling parameter
      that determines whether the system encapsulates or the copolymer and solute
      aggregate separately. The presence of solute particles makes micelles form more
      easily than they would otherwise. Five different mesophases or morphologies are
      possible. The micelle-unimer transition that occurs in a solute-free copolymer
      solvent system is, for moderately hydrophobic solute particles, replaced by a
      transition between a micelle phase and a morphology in which copolymers surround
      a large aggregate of solute particles. The best encapsulation occurs for highly
      hydrophobic solute particles where solutes are dispersed throughout the micelle's
      core. The manner in which our results might be used by experimentalists to
      improve the encapsulation behavior of drug-copolymer systems is discussed.

PMID- 20825215
TI  - Heterologous prime-boost immunizations with a virosomal and an alphavirus
      replicon vaccine.
AB  - Heterologous prime-boost immunization strategies in general establish higher
      frequencies of antigen-specific T lymphocytes than homologous prime-boost
      protocols or single immunizations. We developed virosomes and recombinant Semliki
      Forest virus (rSFV) as antigen delivery systems, each capable of inducing strong
      CTL responses in homologous prime-boost protocols. Here, we demonstrate that a
      heterologous prime-boost with recombinant Semliki Forest virus (rSFV) encoding a
      fusion protein of E6 and E7 of human papillomavirus (HPV) type 16 and virosomes
      containing the HPV16 E7 protein resulted in higher numbers of antigen-specific
      CTL in mice than homologous protocols. Evasion of vector-specific immunity
      appeared to play a role in establishing these high frequencies, as coinduction of
      vector-specific responses during the prime immunization reduced the frequency of
      antigen-specific CTL after a heterologous booster. However, the high numbers of
      CTL initially primed by the heterologous protocols did not correlate with
      enhanced responsiveness to in vitro antigenic stimulation, nor in improved
      cytolytic activity or antitumor responses in vivo compared to a homologous
      protocol with rSFV. This lack of correlation could not be explained by changes in
      numbers of regulatory T cells. However, we observed differences in the
      frequencies of T cell subsets within the E7-specific CD8(+) T cell population,
      e.g. higher frequencies of central memory T cells upon homologous immunizations
      compared to heterologous immunizations. The induction of central memory T cells
      is crucial for a cancer vaccine as these cells are known to rapidly expand upon
      recall stimulation. This study demonstrates that the strongly increased number of
      antigen-specific CTL as induced by heterologous prime-boost immunizations, often
      used as a proof for the enhanced efficacy of such regimes, does not necessarily
      equal superior functional antitumor responses.

PMID- 20825216
TI  - Effects of temperature and alkyl groups of poly(alkyl methacrylate)s on inter-
      and intramolecular interactions of excited singlet states of pyrenyl guest
      molecules.
AB  - Temperature-induced changes in the static and dynamic characteristics of the
      fluorescence from pyrene and N,N-dimethyl-3-(pyren-1-yl)propan-1-amine (PyC3NMe2)
      have been used to determine the locations and mobilities of these probes in the
      anisotropic environments provided by films of 5 poly(alkyl methacrylate) (PAMA)
      polymers in which alkyl is ethyl, butyl, isobutyl, cyclohexyl, and hexadecyl.
      Whereas emission from pyrene reports on the polarity of the guest sites and the
      ability of molecules to diffuse translationally between sites, emission from
      PyC3NMe2 yields information about the fluidity and the shape of the guest sites.
      Data have been obtained from 20 to >400 K, a range that spans the onsets of
      several relaxation processes in the hosts. Those data indicate that the pyrenyl
      groups reside near to ester functionalities in most of the PAMAs, although the
      distance from them (and the main chains) depends upon the bulkiness of the alkyl
      groups. Among the most important conclusions derived from this research is that
      the rates of segmental relaxation phenomena near the probe molecules--and not
      free volume, as was concluded previously from fluorescence measurements in
      polyethylene films--are the dominant contributors to the fluorescence changes. Of
      practical importance, changes in those rates have permitted the onset
      temperatures of many of the relaxation phenomena occurring in the vicinity of the
      probes to be located.

PMID- 20825217
TI  - Bioactivation of isothiazoles: minimizing the risk of potential toxicity in drug
      discovery.
AB  - Compound 1, (7-methoxy-N-((6-(3-methylisothiazol-5-yl)-[1,2,4]triazolo[4,3
      b]pyridazin-3-yl)methyl)-1,5-naphthyridin-4-amine) is a potent, selective
      inhibitor of c-Met (mesenchymal-epithelial transition factor), a receptor
      tyrosine kinase that is often deregulated in cancer. Compound 1 displayed
      desirable pharmacokinetic properties in multiple preclinical species. Glutathione
      trapping studies in liver microsomes resulted in the NADPH-dependent formation of
      a glutathione conjugate. Compound 1 also exhibited very high in vitro NADPH
      dependent covalent binding to microsomal proteins. Species differences in
      covalent binding were observed, with the highest binding in rats, mice, and
      monkeys (1100-1300 pmol/mg/h), followed by dogs (400 pmol/mg/h) and humans (144
      pmol/mg/h). This covalent binding to protein was abolished by coincubation with
      glutathione. Together, these in vitro data suggest that covalent binding and
      glutathione conjugation proceed via bioactivation to a chemically reactive
      intermediate. The cytochrome (CYP) P450 enzymes responsible for this
      bioactivation were identified as cytochrome P450 3A4, 1A2, and 2D6 in human and
      cytochrome P450 2A2, 3A1, and 3A2 in rats. The glutathione metabolite was
      detected in the bile of rats and mice, thus demonstrating bioactivation occurring
      in vivo. Efforts to elucidate the structure of the glutathione adduct led to the
      isolation and characterization of the metabolite by NMR and mass spectrometry.
      The analytical data confirmed conclusively that the glutathione conjugation was
      on the 4-C position of the isothiazole ring. Such P450-mediated bioactivation of
      an isothiazole or thiazole group has not been previously reported. We propose a
      mechanism of bioactivation via sulfur oxidation followed by glutathione attack at
      the 4-position with subsequent loss of water resulting in the formation of the
      glutathione conjugate. Efforts to reduce bioactivation without compromising
      potency and pharmacokinetics were undertaken in order to minimize the potential
      risk of toxicity. Because of the exemplary pharmacokinetic/pharmacodynamic
      (PK/PD) properties of the isothiazole group, initial attempts were focused on
      introducing alternative metabolic soft spots into the molecule. These efforts
      resulted in the discovery of 7-(2-methoxyethoxy)-N-((6-(3-methyl-5
      isothiazolyl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)-1,5-naphthyridin-4
      amine (compound 2), with the major metabolic transformation occurring on the
      naphthyridine ring alkoxy substituent. However, a glutathione conjugate of
      compound 2 was produced in vitro and in vivo in a manner similar to that observed
      for compound 1. Furthermore, the covalent binding was high across species (360,
      300, 529, 208, and 98 pmol/mg/h in rats, mice, dogs, monkeys, and humans,
      respectively), but coincubation with glutathione reduced the extent of covalent
      binding. The second viable alternative in reducing bioactivation involved
      replacing the isothiazole ring with bioisosteric heterocycles. Replacement of the
      isothiazole ring with an isoxazole or a pyrazole reduced the bioactivation while
      retaining the desirable PK/PD characteristics of compounds 1 and 2.

PMID- 20825218
TI  - Synthesis and biological activity of pyrido[3',2':4,5]thieno[3,2-d]pyrimidines as
      phosphodiesterase type 4 inhibitors.
AB  - A series of pyrido[3',2':4,5]thieno[3,2-d]pyrimidines (PTP) has been synthesized
      and tested as phosphodiesterase IV inhibitors (PDE4), a target for the treatment
      of asthma and chronic obstructive pulmonary disease (COPD). Structure-activity
      relationships within this series, leading to an increase of potency on the
      enzyme, are presented. The gem-dimethylcycloalkyl moiety fused to the pyridine
      ring proved to be a key element of the scaffold in order to get a higher affinity
      in the enzyme.

PMID- 20825219
TI  - Oral bioperformance and 21st century dissolution.

PMID- 20825220
TI  - Competitive entry of sodium and potassium into nanoscale pores.
AB  - We have studied the competitive entry of potassium and sodium into carbon
      nanotubes using molecular dynamics simulations. Our results demonstrate how a
      combination of strong sodium hydration coupled with strong potassium-chlorine
      interaction leads to enhanced potassium selectivity at certain diameters. We
      detail the reasons behind this, and show how variation of nanotube diameter can
      cause a switch to sodium selectivity, or even cause a decrease in overall ion
      entry despite an increase in diameter. These results demonstrate the importance
      of considering inter-ion dependence in the theoretical study of pore selectivity
      and show that, with careful design, the practical separation of sodium and
      potassium is possible using diameter variation alone.

PMID- 20825221
TI  - Self-assembled monolayers formed using zero net curvature norbornylogous bridges:
      the influence of potential on molecular orientation.
AB  - A new class of electroactive norbornylogous bridges, with no net curvature, that
      form self-assembled monolayers on gold electrodes were studied by
      electrochemistry and in situ infrared spectroscopy. The influence of the
      electrode potential on the structure and conformation of the self-assembled
      monolayers (SAMs) was investigated. This was performed using two different
      lengths of rigid norbornylogous bridges with terminal ferrocene moieties and
      omega-hydroxyalkanethiols. It was found that single component monolayers of the
      rigid norbornylogous bridges changed their tilt angle with their transition from
      the ferrocene to ferricinium. However, when the norbornylogous SAMs were diluted
      with omega-hydroxyalkanethiols the tilt angle remained unchanged upon oxidation
      of ferrocene to ferricinium. It was also observed that the tilt angle of the
      diluent, omega-hydroxyalkanethiols changed at potentials exceeding 500 mV.

PMID- 20825222
TI  - Structural evolution of (1-NpOH)(n) clusters studied by R2PI and IR dip
      spectroscopies.
AB  - A large-size 1-naphthol cluster, (1-NpOH)(n), with n <= 30 was prepared by using
      a high-pressure pulsed valve. The electronic and vibrational transitions of (1
      NpOH)(n) with n = 3-9 were measured by resonant two-photon ionization (R2PI) and
      ion-detected IR dip spectroscopies. The S(1) <- S(0) R2PI spectrum shows
      partially resolved structures around the origin band in the (1-NpOH)(n) cluster
      with n = 3-8. The (1-NpOH)(3) and the (1-NpOH)(6) clusters show relatively sharp
      origin bands. The structure of (1-NpOH)(3) was determined by comparison of the IR
      dip spectrum with the simulated one by DFT calculation, while those of (1
      NpOH)(n) (n >= 4) were discussed in terms of topological geometries of a hydrogen
      bonded network. Those analyses suggest that (i) the (1-NpOH)(3) cluster has the
      cyclic structure where three 1-NpOH monomers are linked by both the hydrogen
      bonding and the pi...C-H interaction between naphthyl rings and (ii) the (1
      NpOH)(n) cluster with n >= 4 is built up by attaching the 1-NpOH monomers to the
      (1-NpOH)(3) core.

PMID- 20825223
TI  - Single-domain protein A-engineered magnetic nanoparticles: toward a universal
      strategy to site-specific labeling of antibodies for targeted detection of tumor
      cells.
AB  - Highly monodisperse magnetite nanocrystals (MNC) were synthesized in organic
      media and transferred to the water phase by ultrasound-assisted ligand exchange
      with an iminodiacetic phosphonate. The resulting biocompatible magnetic
      nanoparticles were characterized by transmission electron microscopy, dynamic
      light scattering, and magnetorelaxometry, indicating that this method allowed us
      to obtain stable particle dispersions with narrow size distribution and unusually
      high magnetic resonance T(2) contrast power. These nanoparticles were conjugated
      to a newly designed recombinant monodomain protein A variant, which exhibited a
      convincingly strong affinity for human and rabbit IgG molecules. Owing to the
      nature of antibody-protein A binding, tight antibody immobilization occurred
      through the Fc fragment thus taking full advantage of the targeting potential of
      bound IgGs. If necessary, monoclonal antibodies could be removed under controlled
      conditions regenerating the original IgG-conjugatable MNC. As a proof of concept
      of the utility of our paramagnetic labeling system of human IgGs for biomedical
      applications, anti-HER-2 monoclonal antibody trastuzumab was immobilized on
      hybrid MNC (TMNC). TMNC were assessed by immunoprecipitation assay and confocal
      microscopy effected on HER-2-overexpressing MCF-7 breast cancer cells,
      demonstrating excellent recognition capability and selectivity for the target
      membrane receptor.

PMID- 20825224
TI  - Antioxidant and anti-inflammatory phenylpropanoid derivatives from Calamus
      quiquesetinervius.
AB  - Eight new phenylpropanoid derivatives [quiquesetinerviusides A (1), B (2), C (3),
      D (4), and E (5), as well as quiquesetinerviusins A (6), B (7), and C (8)] and
      seven known compounds (8-15), were isolated from an EtOAc extract of Calamus
      quiquesetinervius stems. The structures of 1-8 were elucidated on the basis of 1D
      and 2D-NMR spectroscopic data analysis. Bioassay results showed that 1-5 possess
      weak DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging activity, but potent (.)OH
      radical scavenging activity (IC(50) 3.6-8.4 MUM). Of the tested isolates,
      compounds 4-6 and 9 showed potent inhibition (IC(50) 9.2-29.5 MUM) of LPS
      stimulated NO production when compared with a positive control substance,
      quercetin (IC(50) 34.5 MUM).

PMID- 20825225
TI  - A neuroprotective polysaccharide from Hyriopsis cumingii.
AB  - A water-soluble polysaccharide from Hyriopsis cumingii (HCp) was isolated by hot
      water extraction and ethanol precipitation. We investigated the preliminary
      neuroprotective activity of HCp on cerebral ischemia/reperfusion (I/R)-induced
      rat brain tissue injury using the middle cerebral artery occlusion (MCAO) model.
      The structural analysis showed that the major component of HCp (HP-I) is an alpha
      (1->4)-d-glucan branched with a single alpha-d-glucose at C-6 every five residues
      on average and has a weight-average molecular weight of about 2.65 * 10(5).
      Pharmacological studies revealed that HCp improves and restores nerve function
      impairment, significantly increases brain tissue total superoxide dismutase
      activity, lowers malondialdehyde content effectively, and reduces brain levels of
      caspase-3 mRNA expression in a dose-effect manner, indicating that H. cumingii
      polysaccharide possesses significant neuroprotective effects.

PMID- 20825226
TI  - Graphene as atomic template and structural scaffold in the synthesis of graphene
      organic hybrid wire with photovoltaic properties.
AB  - The dual role of graphene (or reduced graphene oxide) as atomic template and
      structural scaffold in the nucleation and assembly of organic nanostructures is
      demonstrated. The pi-pi stacking interactions between graphene and aromatic
      organic molecules affords synergistic binding interactions, with the host and
      guest assuming the interchangeable roles of atomic template and structural
      scaffold. Beginning with the seeding of organic wires on graphene template, the
      outgrown organic wires in turn act as one-dimensional scaffolds where graphene
      sheets coat around to form a unique graphene-organic hybrid structure. Using this
      pi-assembly approach, we have synthesized one-dimensional hybrid structures
      consisting of graphene-N,N'-dioctyl-3,4,9,10-perylenedicarboximide (PDI) organic
      wires. This hybrid structure shows enhanced performance over its individual
      components in donor-acceptor type (PDI-Graphene/polythiophene) solar cells.

PMID- 20825227
TI  - Superhydrophilic surfaces via polymer-SiO2 nanocomposites.
AB  - A novel procedure for the preparation of superhydrophilic surfaces is described.
      The method employs fabricating the surface from a mixture of silica nanoparticles
      (NPs) and polymers containing reactive trimethoxysilyl (TMOS) groups. Suitable
      polymers include quaternized poly(2-(dimethylamino)ethyl methacrylate) (PQDMAEMA)
      and poly(3-(trimethoxysilyl)propyl methacrylate) (PTMOSPMA). Condensation of the
      TMOS groups in a deposited film occurs under mild conditions and results in
      formation of a cross-linked polymer-SiO(2) nanocomposite coating covalently
      anchored onto a glass substrate. When silica nanoparticles, containing micrometer
      sized agglomerates, are introduced into the film, a hierarchical
      micro/nanostructure within the coating is built up. Superhydrophilic behavior is
      achieved with a high weight ratio of fumed silica NPs or polymer/fumed silica NP
      bilayer coatings. The superhydrophilic surfaces have high stability and
      antifogging behavior and display easy cleaning characteristics. Furthermore, the
      superhydrophilic nanocomposite coatings containing PQDMAEMA exhibit antimicrobial
      properties against E. coli due to the presence of quaternary ammonium groups.

PMID- 20825228
TI  - Experimental verification of force fields for molecular dynamics simulations
      using Gly-Pro-Gly-Gly.
AB  - Experimental NMR verification of MD simulations using 12 different force fields
      (AMBER, CHARMM, GROMOS, and OPLS-AA) and 5 different water models has been
      undertaken to identify reliable MD protocols for structure and dynamics
      elucidations of small open chain peptides containing Gly and Pro. A
      conformationally flexible tetrapeptide Gly-Pro-Gly-Gly was selected for NMR (3)J
      coupling, chemical shift, and internuclear distance measurements, followed by
      their calculations using 2 MUs long MD simulations in water. In addition,
      Ramachandran population maps for Pro-2 and Gly-3 residues of GPGG obtained from
      MD simulations were used for detailed comparisons with similar maps from the
      protein data bank (PDB) for large number of Gly and Pro residues in proteins. The
      MD simulations revealed strong dependence of the populations and geometries of
      preferred backbone and side chain conformations, as well as the time scales of
      the peptide torsional transitions on the force field used. On the basis of the
      analysis of the measured and calculated data, AMBER99SB is identified as the most
      reliable force field for reproducing NMR measured parameters, which are dependent
      on the peptide backbone and the Pro side chain geometries and dynamics.
      Ramachandran maps showing the dependence of conformational populations as a
      function of backbone phi/psi angles for Pro-2 and Gly-3 residues of GPGG from MD
      simulations using AMBER99SB, AMBER03, and CHARMM were found to resemble similar
      maps for Gly and Pro residues from the PDB survey. Three force fields (AMBER99,
      AMBER99phi, and AMBER94) showed the least satisfactory agreement with both the
      solution NMR and the PDB survey data. The poor performance of these force fields
      is attributed to their propensity to overstabilize helical peptide backbone
      conformations at the Pro-2 and Gly-3 residues. On the basis of the similarity of
      the MD and PDB Ramachandran plots, the following sequence of transitions is
      suggested for the Gly backbone conformation: alpha(L) ? beta(PR) ? beta(S) ?
      beta(P) ? alpha, where backbone secondary structures alpha(L) and alpha are
      associated with helices and turns, beta(P) and beta(PR) correspond to the left-
      and right-handed polyproline II structures and beta(S) denotes the fully
      stretched backbone conformation. Compared to the force field dependence, less
      significant, but noteworthy, variations in the populations of the peptide
      backbone conformations were observed. For different solvent models considered, a
      correlation was noted between the number of torsional transitions in GPGG and the
      water self-diffusion coefficient on using TIP3P, TIP4P, and TIP5P models. In
      addition to MD results, we also report DFT derived Karplus relationships for Gly
      and Pro residues using B972 and B3LYP functionals.

PMID- 20825231
TI  - Arsenic-containing chalcophosphate molecular anions.
AB  - We report five new discrete molecular arsenic-based chalcophosphates,
      K(7)As(3)(P(2)Se(6))(4) (1), K(6)As(2)(P(2)Se(6))(3) (2),
      Cs(6)As(2)(P(2)Se(6))(3) (3), and Cs(5)As(P(2)Q(6))(2) [Q = Se (4a) and S (4b)].
      Each of the compounds contains unique complex anions comprised of common building
      blocks that have condensed to produce these anions. Phosphorus forms well-known
      [P(2)Q(6)](4-) moieties in all of the compounds that are bridged by arsenic
      trigonal pyramids in 1 and 2 and distorted octahedra in 3, 4a, and 4b. Although 2
      and 3 have the same molecular formula, the structural difference between the two
      salts is attributed to the size of the alkali metal. The influence of flux
      basicity also seems to play a role in the formation of the molecular anion in 4a
      and 4b, which has been observed with other trivalent main-group elements at the
      octahedral position but only with the highly basic cesium alkali metal as the
      counterion. All structures were determined by single-crystal X-ray diffraction
      and are discussed along with phase-purity powder X-ray diffraction, thermal
      analyses, electronic absorption, and Raman spectroscopy.

PMID- 20825230
TI  - Immobilization of the aminopeptidase from Aeromonas proteolytica on Mg2+/Al3+
      layered double hydroxide particles.
AB  - A novel biomaterial formed by the immobilization of the Aminopeptidase from
      Aeromonas proteolytica (AAP) on synthetic Mg2+ and Al3+ ion-containing layered
      double hydroxide (LDH) particles was prepared. Immobilization of AAP on the LDH
      particles in a buffered, aqueous mixture is rapid such that the maximum loading
      capacity, 1*10(-9) moles of AAP/mg LDH, is achieved in a few minutes. X-ray
      powder diffraction of LDH samples before and after treatment with AAP indicates
      that the enzyme does not intercalate between the layers of LDH, but instead binds
      to the surface. Treatment of AAP/LDH with various amounts of salt in a buffered
      mixture demonstrates that between 15 and 20% of AAP can be removed from the LDH
      by washing the composite material in 0.2 M NaCl. However, the residual AAP
      remains bound to the LDH even at 1 M salt concentrations. A suspension of the
      AAP/LDH biomaterial in 10 mM Tricine buffered, aqueous solution (pH 8.0 and 25
      degrees  C) catalyzes the hydrolysis of l-leucine-p-nitroanilide demonstrating
      that immobilized AAP remains available to substrate and retains its catalytic
      activity. Recycling experiments reveal that the AAP/LDH particles can be
      recovered and reused multiple times without appreciable loss of activity. This
      work provides the foundation for the development of materials that will function
      in the degradation or detection of peptide hormones or neurotoxins.

PMID- 20825233
TI  - Stereochemical surprises in the Lewis acid-mediated allylation of isatins.
AB  - The BF(3).OEt(2)-mediated allylation of isatin with an alpha-chiral allylic
      stannane is diastereo- and enantioselective. Conversely, allylation of any
      substituted isatin employing the identical protocol is not diastereoselective at
      all and only enantioselective for the major diastereomer having syn relative
      configuration. The anti isomer is, however, formed in almost racemic form. Both
      absolute and relative configurations are unambiguously secured by X-ray analysis
      of major isomers, and the stereochemical assignment of the other 3-substituted 3
      hydroxy oxindoles is based on similar NMR spectroscopic characteristics. The
      remarkable observations are rationalized by an acyclic transition state model.

PMID- 20825234
TI  - Toward L-homo-DNA: stereoselective de novo synthesis of beta-L-erythro
      hexopyranosyl nucleosides.
AB  - A novel route to 2',3'-dideoxy-beta-l-erythro-hexopyranosyl nucleosides equipped
      with a 1'-(N(6)-benzoyladenin-9-yl) or a 1'-(thymin-1-yl) moiety has been
      developed. Synthesis of the enantiopure sugar moiety was carried out by a de novo
      approach based on a domino reaction as the key step. N-Glycosidation was explored
      via either nucleobase-transfer mechanism (B = T) or in situ anomerization (B = A
      or T), affording target nucleosides with high overall stereoselectivity.

PMID- 20825235
TI  - Tribute to the research and professional career of Reinhard Schinke.

PMID- 20825239
TI  - The influence of vibrational excitation on the photoisomerization of trans
      stilbene in solution.
AB  - Preparing electronically excited trans-stilbene molecules in deuterated
      chloroform using both one-photon excitation and excitation through an
      intermediate vibrational state explores the influence of vibrational energy on
      excited-state isomerization in solution. After infrared excitation of either two
      quanta of C-H stretch vibration |2nu(CH)> at 5990 cm(-1) or the C-H stretch-bend
      combination |nu(CH) + nu(bend)> at 4650 cm(-1) in the ground electronic state, an
      ultraviolet photon intercepts the vibrationally excited molecules during the
      course of vibrational energy flow and promotes them to the electronically excited
      state. The energy of the infrared and ultraviolet photons together is the same as
      that added in the one-photon excitation. Transient broadband-continuum absorption
      monitors the lifetime of electronically excited molecules. The lifetime of
      excited-state trans-stilbene after one-photon electronic excitation with 33,300
      cm(-1) of energy is (51 +/- 6) ps. The excited-state lifetimes of (55 +/- 9) ps
      and (56 +/- 7) ps for the cases of excitation through |2nu(CH)> and |nu(CH) +
      nu(bend)>, respectively, are indistinguishable from that for the one-photon
      excitation. Vibrational relaxation in the electronically excited state prepared
      by the two-photon excitation scheme is most likely faster than the barrier
      crossing, making the isomerization insensitive to the method of initial state
      preparation.

PMID- 20825240
TI  - A diffusion Monte Carlo study of the O-H bond dissociation of phenol.
AB  - The homolytic O-H bond dissociation energy (BDE) of phenol was determined from
      diffusion Monte Carlo (DMC) calculations using single determinant trial wave
      functions. DMC gives an O-H BDE of 87.0 +/- 0.3 kcal/mol when restricted Hartree
      Fock orbitals are used and a BDE of 87.5 +/- 0.3 kcal/mol with restricted B3LYP
      Kohn-Sham orbitals. These results are in good agreement with the extrapolated
      B3P86 results of Costa Cabral and Canuto (88.3 kcal/mol), the recommended
      experimental value of Borges dos Santos and Martinho Simoes (88.7 +/- 0.5
      kcal/mol), and the G3 (88.2 kcal/mol), CBS-APNO (88.2 kcal/mol), CBS-QB3 (87.1
      kcal/mol) results of Mulder.

PMID- 20825241
TI  - A periodic orbit bifurcation analysis of vibrationally excited isotopologues of
      sulfur dioxide and water molecules: symmetry breaking substitutions.
AB  - Theoretical predictions and assignment of highly excited vibrational states and
      their organization is one of the most important challenges in molecular
      spectroscopy. A systematic procedure to investigate such problems is locating the
      principal families of periodic orbits that emanate from the stationary points of
      the molecule and then following their evolution with the total energy. This
      results in constructing continuation/bifurcation diagrams that assist in locating
      the critical bifurcation energies and to discover new types of vibrational modes.
      Another parameter that may influence the dynamics of a molecule is isotopic mass
      substitution. In this article, we investigate the effect of symmetry breaking by
      isotopic mass substitution of triatomic molecules with C(2v) symmetry in
      classical and quantum dynamics. Sulfur dioxide and water molecules in their
      ground electronic state are studied by employing accurate potential energy
      surfaces. Continuation/bifurcation diagrams of periodic orbits are constructed by
      varying the energy and the mass of one oxygen atom of sulfur dioxide and one
      hydrogen atom of a water molecule. The transition from normal-to-local mode
      vibrations is studied in terms of a pitchfork to a center-saddle elementary
      bifurcation of periodic orbits. The results presented in this article aim to help
      the assignment of experimentally obtained spectra.

PMID- 20825242
TI  - Imaging the inelastic scattering of water with helium. Comparison of experiment
      and theory.
AB  - State-to-state differential cross sections for rotationally inelastic He-H(2)O
      scattering have been measured at 53.3 meV (429 cm(-1)) collision energy, using
      the crossed molecular beam technique. The inelastic events are detected by
      velocity map imaging of nascent H(2)O(+) ions, which are formed by state
      selective (2 + 1) resonance enhanced multiphoton ionization (REMPI) of the
      scattered H(2)O molecules. Raw density images are converted to flux images and
      the extracted differential cross sections are compared with full close-coupling
      calculations of state-to-state cross sections for rotational excitation based on
      a previously published ab initio potential. A hard-shell ellipsoid model is also
      employed to yield a more physical insight useful in interpreting the results. The
      excellent agreement of fully quantum theory and experiment found here for water
      collisions with helium at a collision energy relevant to that of the interstellar
      media place the theoretically determined potential energy surface and the
      collision cross sections extracted using this surface on a firmer basis.

PMID- 20825243
TI  - Toward an improved ground state potential energy surface of ozone.
AB  - A systematic study of the ozone potential energy surface was performed by means
      of high level ab initio techniques. The methods include icMR-CISD and icMR-AQCC
      with all electrons correlated using a full valence CAS reference space and basis
      sets up to sextuple-zeta quality along with extrapolation to the complete basis
      set limit. We computed a dense 3D grid as well as 1D cuts along stretching and
      bending coordinates around the open (C(2v)) equilibrium structure as well as
      along the minimum energy path to dissociation including the transition state and
      the van der Waals minimum region. The detailed analysis of our results confirms
      earlier calculations by the Schinke group and assures that these are not biased
      by deficiencies of the basis set, lack of relativistic corrections, or core
      correlation effects. Finally, we discuss possible sources of error that may
      explain the remaining discrepancies compared to experimental findings.

PMID- 20825244
TI  - Quantum dynamics of a hydrogen molecule inside an anisotropic open-cage
      fullerene: coupled translation-rotation eigenstates and comparison with inelastic
      neutron scattering spectroscopy.
AB  - We report rigorous quantum five-dimensional (5D) calculations of the translation
      rotation (T-R) energy levels and wave functions of H(2) inside aza-thia-open-cage
      fullerene (ATOCF). Translational and rotational excitations of this endohedral
      complex have been measured in a recent inelastic neutron scattering (INS) study,
      enabling direct comparison between theory and experiment. ATOCF has no symmetry,
      and therefore the intermolecular potential energy surface (PES) governing the T-R
      dynamics of H(2) is strongly anisotropic. A pairwise additive PES is employed in
      the calculations. Inspection of the wave functions shows three regular quasi-1D
      translational modes aligned with the Cartesian x, y, and z axes, respectively.
      These and other translational excitations can be assigned with the Cartesian
      quantum numbers v(x), v(y), and v(z). The radial anisotropy of the cage
      environment causes the splitting of the translational fundamental into three
      excitations whose frequencies differ substantially; the z mode directed toward
      the ATOCF orifice has the lowest frequency and is the most anharmonic. All three
      translational modes exhibit negative anharmonicity. The j = 1 rotational level of
      H(2) is also split into a triplet, due to the angular anisotropy of the cage. The
      complete lifting of the degeneracies of the translational fundamental and the j =
      1 triplet of the encapsulated H(2) molecule that emerges from the calculations is
      also observed in the INS spectra of H(2)@ATOCF. The calculated magnitudes of both
      splittings, as well as the energies of the individual sublevels, rotational and
      translational, are in good agreement with the INS data.

PMID- 20825245
TI  - Photolysis of tert-butylthionitrite via excitation to the S(1) and S(2) states
      studied by 3d-REMPI spectroscopy.
AB  - S-Nitrosothiols serve as carriers and donors of NO in several important
      biological signaling systems. In these compounds the S-NO bond is rather labile
      and NO can be released thermally or photochemically. This paper reports on the
      photolytical decomposition of tert-butylthionitrite (t-BuSNO) in the visible and
      near-UV spectral regions. Between 500 and 605 nm several vibronic levels of the
      S(1) (npi*) state were excited, including the electronic origin. At 360 nm t
      BuSNO is excited near the maximum of the first UV band assigned to the S(2)
      (pipi*) state. The velocity distributions of several hundred rovibrational states
      of the NO fragments were recorded with the recently developed 3d-REMPI method. A
      global fit to these data yields populations of the rovibrational states in both
      spin-orbit components of the (2)Pi electronic state of NO as well as their
      velocity distributions and angular anisotropies beta. These data also carry the
      distribution functions for internal and kinetic energy of the counterfragment,
      the t-BuS radical. The range found for the anisotropy parameter confirms the npi*
      character of the visible absorption band (-1.0 < beta < -0.8), and the pipi*
      character of the UV band (beta = 1.2). Mode-specific dissociation has been
      observed for excitation into several vibronic bands of the S(0) -> S(1)
      transition. Some produce NO exclusively in the nu = 0 vibrational ground state,
      whereas some others produce NO almost entirely in the nu = 1 vibrationally
      excited state. It is concluded that photodissociation is faster than relaxation
      of the NO stretch vibration of t-BuSNO in S(1) and that it proceeds on purely
      repulse potential energy surfaces in both electronic states.

PMID- 20825247
TI  - An automated data analysis pipeline for GC-TOF-MS metabonomics studies.
AB  - Recent technological advances have made it possible to carry out high-throughput
      metabonomics studies using gas chromatography coupled with time-of-flight mass
      spectrometry. Large volumes of data are produced from these studies and there is
      a pressing need for algorithms that can efficiently process and analyze data in a
      high-throughput fashion as well. We present an Automated Data Analysis Pipeline
      (ADAP) that has been developed for this purpose. ADAP consists of peak detection,
      deconvolution, peak alignment, and library search. It allows data to flow
      seamlessly through the analysis steps without any human intervention and features
      two novel algorithms in the analysis. Specifically, clustering is successfully
      applied in deconvolution to resolve coeluting compounds that are very common in
      complex samples and a two-phase alignment process has been implemented to enhance
      alignment accuracy. ADAP is written in standard C++ and R and uses parallel
      computing via Message Passing Interface for fast peak detection and
      deconvolution. ADAP has been applied to analyze both mixed standards samples and
      serum samples and identified and quantified metabolites successfully. ADAP is
      available at http://www.du-lab.org .

PMID- 20825246
TI  - Structural analysis of a highly glycosylated and unliganded gp120-based antigen
      using mass spectrometry.
AB  - Structural characterization of the HIV-1 envelope protein gp120 is very important
      for providing an understanding of the protein's immunogenicity and its binding to
      cell receptors. So far, the crystallographic structure of gp120 with an intact V3
      loop (in the absence of a CD4 coreceptor or antibody) has not been determined.
      The third variable region (V3) of the gp120 is immunodominant and contains
      glycosylation signatures that are essential for coreceptor binding and entry of
      the virus into T-cells. In this study, we characterized the structure of the
      outer domain of gp120 with an intact V3 loop (gp120-OD8) purified from Drosophila
      S2 cells utilizing mass spectrometry-based approaches. We mapped the
      glycosylation sites and calculated the glycosylation occupancy of gp120-OD8; 11
      sites from 15 glycosylation motifs were determined as having high-mannose or
      hybrid glycosylation structures. The specific glycan moieties of nine
      glycosylation sites from eight unique glycopeptides were determined by a
      combination of ECD and CID MS approaches. Hydroxyl radical-mediated protein
      footprinting coupled with mass spectrometry analysis was employed to provide
      detailed information about protein structure of gp120-OD8 by directly identifying
      accessible and hydroxyl radical-reactive side chain residues. Comparison of gp120
      OD8 experimental footprinting data with a homology model derived from the ligated
      CD4-gp120-OD8 crystal structure revealed a flexible V3 loop structure in which
      the V3 tip may provide contacts with the rest of the protein while residues in
      the V3 base remain solvent accessible. In addition, the data illustrate
      interactions between specific sugar moieties and amino acid side chains
      potentially important to the gp120-OD8 structure.

PMID- 20825248
TI  - Proteomic definition of the cell wall of Mycobacterium tuberculosis.
AB  - The cell envelope of Mycobacterium tuberculosis (Mtb) is complex and diverse;
      composed of proteins intermingled in a matrix of peptidoglycan, mycolic acids,
      lipids, and carbohydrates. Proteomic studies of the Mtb cell wall have been
      limited; nonetheless, the characterization of resident and secreted proteins
      associated with the cell wall are critical to understanding bacterial survival
      and immune modulation in the host. In this study, the cell wall proteome was
      defined in order to better understand its unique biosynthetic and secretion
      processes. Mtb cell wall was subjected to extraction with organic solvents to
      remove noncovalently bound lipids and lipoglycans and remaining proteins were
      solubilized with either SDS, Guanidine-HCl, or TX-114. These extracts were
      analyzed by two-dimensional gel electrophoresis and mass-spectrometry and
      resulted in the identification of 234 total proteins. The lipoproteome of Mtb,
      enriched in the TX-114 extract, was further resolved by multidimensional
      chromatography and mass spectrometry to identify an additional 294 proteins. A
      query of the 528 total protein identifications against Neural Network or Hidden
      Markov model algorithms predicted secretion signals in 87 proteins.
      Classification of these 528 proteins also demonstrated that 35% are involved in
      small molecule metabolism and 25% are involved in macromolecule synthesis and
      degradation building upon evidence that the Mtb cell wall is actively engaged in
      mycobacterial survival and remodeling.

PMID- 20825249
TI  - NMR solution structures of clustered abasic site lesions in DNA: structural
      differences between 3'-staggered (-3) and 5'-staggered (+3) bistranded lesions.
AB  - Ionizing radiation produces a distinctive pattern of bistranded clustered lesions
      in DNA. A relatively low number of clustered lesions may be lethal to cells when
      compared to a larger number of single lesions. Enzyme cleavage experiments
      suggest that the orientation of bistranded lesions causes differential
      recognition and removal of these lesions. Like that of a previous study of
      bistranded abasic site lesion [Hazel, R. D., Tian, K., and de los Santos, C.
      (2008) Biochemistry 47, 11909-11919], the aim of this investigation was to
      determine the structures of two DNA duplexes each containing two synthetic
      apurinic/apyrimidinic (AP) residues, positioned on opposite strands and separated
      by two base pairs. In the first duplex, the AP residues are staggered in the 3'
      orientation [-3 duplex, (AP)(2)-3 duplex], while in the second duplex, the AP
      residues are staggered in the 5' orientation [+3 duplex, (AP)(2)+3 duplex]. NOESY
      spectra recorded in 100 and 10% D(2)O buffer solutions allowed the assignment of
      the nonexchangeable and exchangeable protons, respectively, for each duplex.
      Cross-peak connectivity in the nonexchangeable proton spectra indicates that the
      duplex is a regular right-handed helix with the AP residues and orphan bases
      located inside the duplexes. The exchangeable proton spectra establish the
      formation of Watson-Crick G.C alignment for the two base pairs between the lesion
      sites in both duplexes. Distance-restrained molecular dynamics simulation
      confirmed the intrahelical orientations of the AP residues. The proximity of the
      AP residues across the minor groove of the -3 duplex and across the major groove
      in the +3 duplex is similar to their locations in the case of -1 and +1 clusters.
      This difference in structure may be a key factor in the differential recognition
      of bistranded AP lesions by human AP endonuclease.

PMID- 20825250
TI  - Proteomic signatures uncover hydrogen peroxide and nitric oxide cross-talk
      signaling network in citrus plants.
AB  - Hydrogen peroxide (H(2)O(2)) and nitric oxide ((*)NO) elicit numerous processes
      in plants. However, our knowledge of H(2)O(2) and (*)NO-responsive proteins is
      limited. The present study aimed to identify proteins whose accumulation levels
      were regulated by these signaling molecules in citrus leaves. To address this
      question, hydroponically grown citrus plants were treated by incubating their
      roots in the presence of H(2)O(2) or the (*)NO donor, sodium nitroprusside (SNP).
      Both treatments induced H(2)O(2) and (*)NO production in leaves, indicating
      occurrence of oxidative and nitrosative stress conditions. However, treated
      plants maintained their normal physiological status. The vascular system was
      shown to be involved in the H(2)O(2) and (*)NO systemic signaling as evidenced by
      real-time labeling of the two molecules. Comparative proteomic analysis
      identified a number of proteins whose accumulation levels were altered by
      treatments. They were mainly involved in photosynthesis, defense and energy. More
      than half of them were commonly modulated by both treatments, indicating a strong
      overlap between H(2)O(2) and (*)NO responses. Using a redox proteomic approach,
      several proteins were also identified as being carbonylation targets of H(2)O(2)
      and SNP. The analysis reveals an interlinked H(2)O(2) and (*)NO proteins network
      allowing a deeper understanding of oxidative and nitrosative signaling in plants.

PMID- 20825251
TI  - Ecopharmacovigilance for better health.

PMID- 20825252
TI  - Safety, tolerability and pharmacokinetics of sugammadex using single high doses
      (up to 96 mg/kg) in healthy adult subjects: a randomized, double-blind,
      crossover, placebo-controlled, single-centre study.
AB  - BACKGROUND AND OBJECTIVE: Sugammadex facilitates rapid reversal of rocuronium-
      and vecuronium-induced neuromuscular blockade. This study aimed to evaluate the
      safety, tolerability and pharmacokinetics of high doses of sugammadex (up to 96
      mg/kg) in healthy subjects. METHODS: In this randomized, double-blind, crossover,
      placebo-controlled, single-centre study, 13 healthy adults were scheduled to
      receive three single intravenous doses of sugammadex in ascending order (32, 64
      and 96 mg/kg) and placebo (interspersed between sugammadex doses), each separated
      by a 1-week washout period. Subjects were randomized to one of four treatment
      sequences, receiving doses as constant rate infusions over 5 minutes. Safety was
      assessed by adverse events, 12-lead ECGs, vital signs, and blood and urine
      laboratory parameters; pharmacokinetics were evaluated from blood and urine
      sugammadex concentrations. RESULTS: Sugammadex was well tolerated in 12 of the 13
      subjects, with adverse events being generally mild, of limited duration and more
      frequent at higher doses. The most common adverse event was dysgeusia; there were
      no serious adverse events. One subject was withdrawn from the study after
      experiencing several adverse events following first exposure to sugammadex,
      related to a probable hypersensitivity reaction to sugammadex. Pharmacokinetics
      were dose linear over the dose range studied (32-96 mg/kg), and 90-93% of the
      sugammadex dose was excreted unchanged in urine within 48 hours. CONCLUSION: High
      doses of sugammadex (up to 96 mg/kg) were well tolerated in 12 of the 13
      subjects. One male subject experienced several adverse events associated with a
      probable hypersensitivity reaction to sugammadex. Pharmacokinetics were dose
      linear over the range 32-96 mg/kg, with elimination predominantly via the renal
      route.

PMID- 20825253
TI  - Establishment and comparison of delayed-type hypersensitivity models in the
      B6C3F1 mouse.
AB  - The objective of these studies was to establish and compare delayed-type
      hypersensitivity (DTH) models, using keyhole limpet hemocyanin (KLH), sheep red
      blood cells (SRBC), and Candida albicans as sensitizing antigens, for their
      capability to assess a DTH response (utilizing footpad swelling as the endpoint)
      with minimal confounding factors resulting from antigen-specific antibody (Ab)
      production. The key elements of the DTH are the sensitization dose, time interval
      between sensitization and challenge [i.e. the challenge interval (CI)], and the
      challenge dose. Models were established by first determining the challenge dose,
      or the amount of antigen that produced no greater footpad swelling 24-h post
      injection than the trauma induced by injection of physiological saline. Time
      course studies determined the CI that produced a peak response for each antigen.
      Dose-response sensitization studies were conducted to determine the optimum
      sensitization concentration (i.e. maximum footpad swelling with minimal impact by
      antigen-specific Ab production). Footpad swelling decreased dose-responsively
      with increasing KLH sensitization concentration and corresponded to a dose
      responsive increase in KLH-specific Ab levels. In the SRBC model, footpad
      swelling decreased at the high dose (1 x 109 SRBC/mouse), and a corresponding
      increase in SRBC-specific Ab was observed at this dose level. A dose-responsive
      increase in footpad swelling was observed in the C. albicans model up to 3 x 107
      organisms/mouse, while antigen-specific antibody levels were not different from
      background (unsensitized) levels following sensitization with any concentration
      of C. albicans (up to 1.2 x 108 organisms/mouse, the highest concentration
      tested). Finally, each model was evaluated for its ability to detect
      immunosuppression following exposure to benzo[a]pyrene (B[a]P), with the C.
      albicans model demonstrating greater sensitivity than the other models. These
      results indicate that, of the three models examined here, the C. albicans DTH
      model may be the most appropriate model for evaluating effects on cell-mediated
      immunity when conducting immunotoxicological investigations.

PMID- 20825254
TI  - Twenty-five years of active laser prevention of scars: what have we learned?
AB  - BACKGROUND AND OBJECTIVES: Cosmetic results after skin surgery are essential for
      patient satisfaction. Since 1983, different lasers have been used to accelerate
      and improve the healing process in surgical scars. This article aims to review
      the different laser therapies available for preventive treatment of scars.
      METHODS: A Medline literature search was performed on laser scar prevention with
      cross-referencing. RESULTS: Different lasers have been used for the preventive
      treatment of scars. Both the pulsed dye laser (PDL) (585 and 595 nm) and laser
      assisted skin healing (LASH) (810 nm) provide excellent results. The mechanism of
      action, side effects and clinical applications are carefully reviewed in this
      article. Ease of the procedure, practical application of the laser and price of
      the therapy are then discussed for both types of laser. CONCLUSION: Two different
      lasers have mostly been used for the preventive treatment of scars. It appears
      that the use of laser energy in the early phase of the healing process is
      critical in the improvement of the resulting scar. More research is still
      warranted to understand the mechanisms of action potentially leading to scarless
      healing. Finally, the widespread, routine use of this technique will largely
      depend on the ease of use of the system.

PMID- 20825255
TI  - Addressing recent concerns in comparative studies of botulinum toxin type A.

PMID- 20825256
TI  - Treatment of hypertrophic scars and keloids with a fractional CO2 laser: a
      personal experience.
AB  - Keloids and hypertrophic scars are both abnormal wound responses in predisposed
      individuals but they differ in that keloids extend beyond the original wound and
      almost never regress, while hypertrophic scars remain within the original wound
      and tend to regress. How keloids grow is not totally clear because there is no
      animal model; in fact, keloids affect only humans. Different injuries can result
      in keloids, including burns, surgery, ear piercing, lacerations, abrasions,
      tattooing, vaccinations, injections, insect bites and any process causing skin
      inflammation (chicken pox, acne, folliculitis, zoster). Skin or wound tension is
      considered a critical factor in the formation of keloids and hypertrophic scars.
      This study is based on eight consecutive patients (four females and four males,
      F:M = 1:1) with a total of 12 keloids. All of whom were treated monthly with a
      MiXto SX CO(2) laser, using 13 W of power, 8 SX of index and 40% coverage
      (density) in combination with Same Plast Gel((r)) twice a day. Each scar required
      12 treatments, and all the patients, followed up for 1 year after the last
      treatment, had optimum results and no recurrence.

PMID- 20825257
TI  - Glycolic acid peels versus amino fruit acid peels for acne.
AB  - INTRODUCTION: Chemical exfoliation resulting in the reduction of keratotic plugs
      serves as a second-line treatment used as an adjunct to anti-acne agents. This
      study was designed to compare the therapeutic effects of glycolic acid (GA) peels
      and amino fruit acid (AFA) peels in patients with acne vulgaris. METHODS: In this
      single-blind, randomized, right-left comparison study, 24 patients received 12
      serial peels (GA and AFA, at concentrations from the lowest to the highest) on
      the two halves of the face at 2-week intervals for 6 months. In addition,
      cutaneous tolerability assessments during the applications and the patient
      preference test between both peeling methods at the end of the study were
      performed. RESULTS: There was a statistically significant decrease in the number
      of non-inflamed lesions with GA following the first month and with AFA following
      the second month (p < 0.05). The decrease in the number of inflamed lesions was
      statistically significant with GA at the end of the fifth and sixth months and
      with AFA only at the end of the fifth month (p < 0.05). When the two applications
      were compared with each other, there was not a statistically significant
      difference in terms of non-inflamed and inflamed lesions (p > 0.05). During the
      application, it was observed that AFA peels caused fewer problems than GA peels
      did. AFA concentrations were increased more rapidly and more sessions were
      performed at the highest concentration of AFA. CONCLUSION: Based on the results
      of this study, we can state that both GA and AFA peels are efficacious for
      comedonal acne. And, compared to a GA peel, an AFA peel is less irritating and
      better tolerated.

PMID- 20825258
TI  - A novel fractional micro-plasma radio-frequency technology for the treatment of
      facial scars and rhytids: a pilot study.
AB  - INTRODUCTION: Fractional ablative and non-ablative lasers have gained popularity
      in the treatment of acne scars and rhytids due to their efficacy and improved
      tolerability. Plasma and radio frequency (RF) have also emerged as methods for
      ablative or non-ablative energy delivery. We report preliminary experience with a
      novel fractional micro-plasma RF device for the treatment of facial acne scars
      and rhytids. METHODS: Sixteen patients with facial acne scars or rhytids were
      treated at 4-week intervals. Treatment parameters were titrated to an immediate
      end point of moderate erythema. The clinical end point for cessation of treatment
      was the attainment of satisfactory clinical results. Results were monitored
      photographically up to 3 months after treatment. RESULTS: Acne scars showed
      marked improvement after two to four treatments. Facial rhytids demonstrated
      reduced depth after two treatments and marked improvement after four treatments.
      Treatment was well tolerated by all participants, with transient erythema and
      short downtime. These results provide initial evidence for the safety and
      effectiveness of fractional micro-plasma RF as a low-downtime and well-tolerated
      modality for the treatment of acne scars and facial rhytids.

PMID- 20825259
TI  - An efficacy comparison of hair removal utilizing a diode laser and an Nd:YAG
      laser system in Chinese women.
AB  - BACKGROUND: The 800 nm diode laser and the 1064 nm Nd:YAG laser have been used
      successfully for hair removal for many years. OBJECTIVE: To compare the efficacy
      of a diode laser with a Nd:YAG laser regarding axillary fossa hair removal in
      Chinese women. METHODS: Twenty-nine Chinese women underwent three treatment
      sessions at 4-week intervals with a diode laser (34-38 J/cm(2)) on one side and a
      Nd:YAG laser (34-40 J/cm(2)) on the other side. Assessments included the
      reduction of hair diameter following treatment, the regrowth rate in hair length,
      total hair reduction and the immediate pain associated with the treatments.
      RESULTS: At follow-up visit number 1 (4 weeks after the first session), the
      average reduction in hair diameter on the diode laser side and the Nd:YAG laser
      side was 2.44 MUm and -0.6 MUm, respectively. The regrowth rates of the hair were
      61.93 MUm/day and 59.84 MUm/day, respectively, which were not statistically
      significant (p > 0.05). At follow-up visit number 1, hair reduction was 60.09%
      and 41.44%, respectively. At follow-up visit number 2 (4 weeks after the second
      session), hair reduction was noted to be 78.56% and 64.50%, respectively, which
      were both statistically significant (p < 0.05). Immediate pain scores at the
      first session were 6.97 and 6.17, respectively; at the second session were 5.48
      and 6.69, respectively; and at the third session were 5.76 and 7.45,
      respectively; all statistically significant (p < 0.05). CONCLUSIONS: The diode
      laser showed more efficacy and was found to be more comfortable than the Nd:YAG
      laser for axillary fossa hair removal in Chinese women.

PMID- 20825260
TI  - A validated facial grading scale: the future of facial ageing measurement tools?
AB  - Validated, standardized scales for measurement of ageing and response to cosmetic
      procedures are lacking. Numerous scales have been published and, while they allow
      intra-study comparisons, almost all remain non-validated, and their heterogeneity
      makes comparisons across studies impossible. A set of validated, objective,
      quantitative scales has been developed in association with experts from different
      specialties within aesthetic medicine. These scales allow evaluation of the key
      signs of ageing that cause individuals to seek cosmetic procedures. Each scale is
      a five-point photonumeric scale based on computer-simulated photographs
      incorporating each aspect to be evaluated in a stepwise manner. Validation
      studies show that these scales have good intra- and inter-rater reliability, with
      intra-class correlation coefficients generally in the range 0.85-0.95, and
      similar test-retest correlations.

PMID- 20825261
TI  - Histological evidence for skin rejuvenation using a combination of pneumatic
      energy, broadband light, and growth factor therapy.
AB  - BACKGROUND AND OBJECTIVE: A variety of laser or light-based devices have been
      developed for skin rejuvenation. This study evaluates the efficacy (at the
      microscopic level) of a combination of pneumatic energy, broadband light, and
      profusion tip-delivered epidermal growth factor (EGF). METHODS: Healthy adult
      Japanese volunteers were recruited for this study. The posterior parts of the
      left and right arms were treated with a device that combines pneumatic energy and
      broadband light (Isolaz device). The left arms were also treated with EGF through
      a tip. Each subject received four treatments at 10-day intervals. Biopsy
      specimens obtained 3 weeks after the second treatment and 3 weeks after the
      fourth treatment were examined for histological study. RESULTS: After two
      treatments, elastin fibers and fibroblasts in the dermal papillary layers of the
      left arms were increased compared to the right arms. A mean of 173.9 cells
      positive for proliferating cell nuclear antibody (PCNA) were observed on the left
      arm compared to 101.0 on the right arm. After the fourth treatment, angiogenesis
      and increased collagen fibers were observed in the dermal papillary layers of
      both arms. CONCLUSION: Four treatments with the addition of the profusion tip
      appear to hasten new collagen and elastin fiber formation, and the increase of
      PCNA positive cells so that dermal remodeling begins at an earlier stage than
      with the Isolaz alone.

PMID- 20825262
TI  - Up-regulation of the vascular cell adhesion molecule-1 (VCAM-1) induced by
      Theiler's murine encephalomyelitis virus infection of murine brain astrocytes.
AB  - The present article reports the up-regulation of the expression of the vascular
      cell adhesion molecule-1 (VCAM-1) by SJL/J mouse brain astrocytes infected with
      Theiler's murine encephalomyelitis virus (TMEV). Complementary RNA (cRNA) from
      mock- and TMEV-infected cells was hybridized to the Affymetrix whole murine
      genome U74v2 DNA microarray. Hybridization data analysis revealed background
      expression in untreated cells and the up-regulation of three sequences coding for
      VCAM-1, as described by the SCOP (Structural Classification Of Proteins)
      database. The authors further studied its regulation, confirming and validating
      their mRNA increase by reverse transcriptase-polymerase chain reaction (RT-PCR)
      and quantitative real-time RT-PCR. The presence of the 100-kDa VCAM-1 protein in
      mock- and TMEV-infected cells was demonstrated in the cell membrane by a specific
      cell-based enzyme-linked immunosorbent assay (ELISA), in addition to flow
      cytometry and confocal immunohistochemistry. Further, Western blots were used to
      quantify the amount of VCAM-1 molecules in cell extracts. All these data
      demonstrated a mean 75% increase in the expression of VCAM-1 on the surface of
      TMEV-infected cells. Three inflammatory cytokines, interleukin-1alpha (IL
      1alpha), interferon gamma (IFNgumma), and specially tumor necrosis factor alpha
      (TNF-alpha), some of which are also induced by TMEV in astrocytes (IL-1alpha and
      TNF-alpha), were potent inducers of VCAM-1 expression. To demonstrate whether the
      VCAM-1 molecules were biologically active, mediating adhesion to other cells as
      the integrin alpha4-expressing CD4+ T lymphocytes, the authors used a cell
      adhesion test. It was also demonstrated by immunohistochemistry that in vivo VCAM
      1 expression is enhanced after TMEV intracraneal infection. The present data show
      a small but statistically significant overexpression of VCAM-1 after astrocyte
      infection with TMEV that could play a significant role in vivo.

PMID- 20825263
TI  - Psychiatrists' relationships with industry: the principal-agent problem.
AB  - Psychiatrists' relationships with the pharmaceutical and device industries have
      been a growing focus of attention, with questions raised about the impact of
      those relationships on prescribing practices, diagnostic criteria, practice
      guidelines, continuing education, conduct and reporting of research, and
      patients' and public trust. Indeed, these concerns exist for the medical
      profession as a whole, with various remedial measures proposed. We suggest that
      such relationships can be understood as giving rise to a "principal-agent
      problem," which occurs when an agent (here, a physician) is engaged to advance
      the interests of another party, the principal (typically a patient), but also
      faces incentives to promote other interests. Studies suggest that at least some
      relationships--which include attending industry-sponsored presentations, meeting
      with marketing representatives, and accepting samples--can alter psychiatrists'
      and other physicians' behavior in ways that can compromise patients' interests,
      and that industry-funded research may create bias in the medical literature.
      These effects are difficult to detect in specific cases, however, because of
      asymmetries of information and may not be apparent even to physicians themselves.
      Principal-agent analysis suggests that the possible responses to such problems,
      including appeals to ethical principles, monitoring behavior, and managing risk
      inducing situations, should include consideration of aligning agents' incentives
      with principals' interests. This type of analysis underscores the similarity of
      the issues raised by physicians' relationships with industry to problems that
      arise more generally in society, thus reducing physicians' potential affective
      responses to these issues and efforts to address them. Finally, such analysis
      directs attention to the benefits and costs of each alternative, thereby
      encouraging reliance on evidence as a basis for policy.

PMID- 20825264
TI  - The pharmacological treatment of bipolar disorder: the question of modern
      advances.
AB  - INTRODUCTION: Lithium has been the mainstay of treatment for patients with
      bipolar disorder in the United States since 1970. Major treatment guidelines
      recommend lithium as a first-line treatment for mania and maintenance treatment
      of bipolar disorder, yet lithium has fallen out of favor while other agents have
      grown in popularity. The purpose of this review is to examine the evidence for
      treatments that were available in 1970 and to determine if the field has made any
      significant advance in the treatment of mania, bipolar depression, and
      maintenance. METHODS: We conducted a MEDLINE search through 2009, and examined
      only English-language, randomized/controlled, placebo, or comparison studies.
      Tolerability as a factor was not considered for this review. RESULTS: Lithium,
      valproate, benzodiazepines, and antipsychotics have been reported effective for
      mania-which was essentially the state of the field in 1970. Despite an FDA
      indication for the use of lamotrigine for depression and depression maintenance,
      the supporting evidence is conflicting. For bipolar maintenance, the evidence is
      overwhelming in support of lithium and very thin for valproate and carbamazepine.
      There is emerging evidence that several atypical antipsychotics may have efficacy
      in prevention. DISCUSSION: The gold standard for treating bipolar disorder in
      1970 was lithium, and the gold standard in 2009 remains lithium. Newer agents may
      increase our armamentarium to some extent, but it is not clear if they represent
      a major advance in treatment. They still need to be tested against the gold
      standard.

PMID- 20825265
TI  - Olfactory dysfunction in schizophrenia: a review of neuroanatomy and
      psychophysiological measurements.
AB  - Olfactory processing is thought to be mediated via the frontal and temporolimbic
      brain regions, both of which, as well as olfactory dysfunction, are implicated in
      schizophrenia. Likewise, several empirical studies of olfactory dysfunction--in
      particular, olfactory deficits in identification, odor detection threshold
      sensitivity, and odor memory, along with associated brain structural changes-
      have been conducted to illuminate the pathophysiology of schizophrenia. These
      anomalies have been investigated, more recently, as possible biological markers
      of that disabling illness. This article summarizes recent research on
      neuroimaging changes associated with olfactory impairments in schizophrenia
      patients and on related functional changes in psychophysiological measurements
      (e.g., odor identification, odor discrimination, odor detection threshold, and
      odor memory). The possible role of these changes as biological markers of the
      disorder will be discussed, as will potentially productive directions for future
      research.

PMID- 20825267
TI  - Immigration trauma, substance abuse, and suicide.

PMID- 20825266
TI  - Glutamatergic modulators: the future of treating mood disorders?
AB  - Mood disorders such as bipolar disorder and major depressive disorder are common,
      chronic, and recurrent conditions affecting millions of individuals worldwide.
      Existing antidepressants and mood stabilizers used to treat these disorders are
      insufficient for many. Patients continue to have low remission rates, delayed
      onset of action, residual subsyndromal symptoms, and relapses. New therapeutic
      agents able to exert faster and sustained antidepressant or mood-stabilizing
      effects are urgently needed to treat these disorders. In this context, the
      glutamatergic system has been implicated in the pathophysiology of mood disorders
      in unique clinical and neurobiological ways. In addition to evidence confirming
      the role of the glutamatergic modulators riluzole and ketamine as proof-of
      concept agents in this system, trials with diverse glutamatergic modulators are
      under way. Overall, this system holds considerable promise for developing the
      next generation of novel therapeutics for the treatment of bipolar disorder and
      major depressive disorder.

PMID- 20825269
TI  - Direct and indirect costs of employees with treatment-resistant and non-treatment
      resistant major depressive disorder.
AB  - OBJECTIVE: Treatment-resistant depression (TRD) imposes substantial cost from the
      perspective of employers. The objective of this study was to assess direct
      healthcare costs and indirect (disability and medical-related absenteeism) costs
      associated with TRD compared with non-treatment-resistant major depressive
      disorder (MDD). METHODS: Employees with one or more inpatient, or two or more
      outpatient/other MDD diagnoses (ICD-9-CM: 296.2x, 296.3x) from 2004 through 2007,
      ages 18-63 years, were selected from a claims database. Employees who initiated a
      third antidepressant following two antidepressant treatments of adequate dose and
      duration or who met published TRD criteria were classified as TRD likely (N =
      2312). The index date was the date of the first antidepressant, starting
      1/1/2004. The control group was an age- and sex-matched cohort of employees with
      MDD but without TRD. All had continuous eligibility during the 6-month pre-index
      (baseline) and 24-month post-index (study) period. McNemar tests were used to
      compare baseline comorbidities. Wilcoxon signed-rank tests were used to compare
      costs from employer perspective. RESULTS: TRD-likely employees were on average 48
      years old, and 64.8% were women. Compared with MDD controls, TRD-likely employees
      had significantly higher rates of mental-health disorders, chronic pain,
      fibromyalgia, and higher Charlson Comorbidity Index. Average direct 2-year costs
      were significantly higher for TRD-likely employees ($22,784) compared with MDD
      controls ($11,733), p < 0.0001. Average indirect costs were also higher among TRD
      likely employees ($12,765) compared with MDD controls ($6885), p < 0.0001.
      LIMITATIONS: Limitations of claims data related to accuracy of diagnosis coding
      and lack of clinical information apply to this study. CONCLUSIONS: Based on
      comorbidities and healthcare resources used, patients with TRD appeared to
      represent a clinically complex subgroup of individuals with MDD. TRD was
      associated with significant cost burden.

PMID- 20825268
TI  - Association between apolipoprotein E4 genotype and human immunodeficiency virus
      associated dementia in younger adults starting antiretroviral therapy in South
      Africa.
AB  - It is not known whether the apolipoprotein E (ApoE) &#x03B5;4 allelic variant is
      associated with human immunodeficiency virus (HIV)-associated dementia (HAD) in a
      South African population, where HIV clade C is predominant. ApoE genotyping was
      performed on 144 participants in a larger study of HIV-associated neurocognitive
      disorders (HAND). There was a lower frequency of the &#x03B5;2 and &#x03B5;3
      alleles in the HIV-positive group, compared to a group of 300 community-based
      newborn infants. There were no differences in ApoE genotype across different
      categories of HAND. The &#x03B5;4 allelic variant was less common in individuals
      with HAD than in those without HAD. These findings suggest that the &#x03B5;4
      allelic variant in HIV-positive individuals is not associated with the
      development of HAD in Southern Africa.

PMID- 20825270
TI  - Clinical burden of venous thromboembolism.
AB  - BACKGROUND: Venous thromboembolism (VTE), which includes deep vein thrombosis and
      pulmonary embolism (PE), is a major cause of morbidity and mortality. VTE is a
      common disorder, with an estimated annual incidence of approximately 5-12 persons
      per 10,000. The prognosis for patients who develop VTE is exacerbated by the risk
      of recurrent VTE, post-thrombotic syndrome and chronic pulmonary hypertension as
      a long-term complication of PE. SCOPE: To assess the clinical burden of VTE a
      literature search was carried out to identify references published between 1997
      and 2008 using Medline, the Cochrane Library and the Health Economic Evaluations
      Database. FINDINGS: VTE is a frequent clinical problem, both in the general
      population, in hospitalised patients and in particular in patients undergoing
      major orthopaedic surgery, after trauma, or those with malignancy, and related
      complications are frequent. VTE imposes significant consequences on patients and
      on the healthcare systems that support them - extending hospital stays and
      precipitating additional hospitalisations. Limitations of the review are that the
      sources quoted may not adequately reflect all publications and all perspectives
      on the topic. CONCLUSIONS: Even among high-risk groups it is not possible to
      identify individuals who will go on to develop VTE, and, therefore,
      thromboprophylaxis is a recommended component of the management of high-risk
      patients. Ensuring patients receive safe, effective, easily administered
      antithrombotic therapy both in hospital and post-discharge, for a sufficient
      length of time, should be central to any strategy to reduce incident or recurrent
      VTE and minimise the risk of long-term complications.

PMID- 20825271
TI  - Primary prevention of cardio-metabolic diseases in general practice: a Dutch
      survey of attitudes and working methods of general practitioners.
AB  - BACKGROUND: To study the attitudes and working methods of general practitioners
      (GPs) in primary prevention of cardiovascular diseases, diabetes mellitus and
      chronic kidney diseases. METHODS: A questionnaire with questions about attitude
      and working methods in the primary prevention of cardiovascular diseases,
      diabetes mellitus and chronic kidney diseases in general practice was sent to a
      representative sample of 1,100 Dutch GPs. The questionnaire was developed in
      collaboration with experts in general practice, cardiovascular disease, diabetes
      and kidney disease. RESULTS: A total of 330 GPs completed and returned the
      questionnaire (30% response). Only a quarter of the GP's actively invite patients
      for preventive measurements. Preventive measures are mainly performed by the GP
      when a patient asks for it or when patients visit a GP for other complaints. The
      main reasons for performing preventive tests were a positive family history,
      obesity and smoking. Most GPs consider detection of these diseases as worthwhile,
      but detection should particularly focus on the group of patients with the highest
      risk on these diseases. CONCLUSION: GPs have a positive attitude towards primary
      prevention of cardiovascular diseases, diabetes mellitus and chronic kidney
      diseases, but primary prevention should be focused on patients at risk.

PMID- 20825272
TI  - Differences in antibiotic treatment and utilization of diagnostic tests in Dutch
      primary care between natives and non-western immigrants.
AB  - BACKGROUND: Different expectations and demands of non-western immigrants may
      prompt physicians to deviate from their routine clinical management strategies
      resulting in more diagnostic tests and higher prescription rates. Antibiotic
      prescription is of specific importance, since overuse of antibiotics is a major
      public health concern. No data are available about possible differences in
      antibiotic prescription rates between natives and non-western immigrants in
      Europe. OBJECTIVES: To determine whether ethnic origin is an independent
      determinant for the frequency of antibiotic treatment and additional diagnostic
      tests in primary care patients with infectious diseases. METHODS: In this cross
      sectional study, 1015 non-western immigrants were compared to 995 native Dutch,
      all selected from the Utrecht Health Project database. Data were analysed using
      multiple logistic regression analyses. Antibiotics most frequently used in Dutch
      primary care were included in the analyses. For the analyses of additional
      diagnostic tests, only respiratory tract infections were included, since these
      are the most common infectious diseases for which general practitioners are
      contacted. RESULTS: First generation non-western immigrants were more likely to
      undergo diagnostic tests and received more antibiotics than native Dutch
      (respectively OR: 2.08; 95% CI: 1.64-2.63; and OR: 1.31; 95% CI: 1.04-1.65). No
      differences were found for the second generation immigrants. The results found
      were independent of potential confounders. CONCLUSIONS: The highest rates of
      antibiotic prescription and diagnostic tests concern first generation non-western
      immigrants. In order to promote a rational and restricted use of antibiotics in
      outpatients first generation immigrants should be a prioritized target group.

PMID- 20825274
TI  - Series: The research agenda for general practice/family medicine and primary
      health care in Europe. Part 4. Results: specific problem solving skills.
AB  - The 'Research Agenda for General Practice/Family Medicine and Primary Health Care
      in Europe' summarizes the evidence relating to the core competencies and
      characteristics of the Wonca Europe definition of GP/FM, and its implications for
      general practitioners/family doctors, researchers and policy makers. The European
      Journal of General Practice publishes a series of articles based on this
      document. The previous articles presented background, objectives, and
      methodology, as well results on 'primary care management' and 'community
      orientation' and the person-related core competencies of GP/FM. This article
      reflects on the general practitioner's 'specific problem solving skills'. These
      include decision making on diagnosis and therapy of specific diseases, accounting
      for the properties of primary care, but also research questions related to
      quality management and resource use, shared decision making, or professional
      education and development. Clinical research covers most specific diseases, but
      often lacks pragmatism and primary care relevance. Quality management is a
      stronghold of GP/FM research. Educational interventions can be effective when
      well designed for a specific setting and situation. However, their message that
      'usual care' by general practitioners is insufficient may be problematic. GP and
      their patients need more research into diagnostic reasoning with a step-wise
      approach to increase predictive values in a setting characterized by uncertainty
      and low prevalence of specific diseases. Pragmatic comparative effectiveness
      studies of new and established drugs or non-pharmaceutical therapy are needed.
      Multi-morbidity and complexity should be addressed. Studies on therapy,
      communication strategies and educational interventions should consider impact on
      health and sustainability of effects.

PMID- 20825280
TI  - Expansion of human hematopoietic cells from umbilical cord blood using roller
      bottles in CO2 and CO2-free atmosphere.
AB  - In this work, we evaluated the expansion of human hematopoietic stem cells from
      umbilical cord blood in roller bottles. The Iscove's modified Dulbecco's medium,
      the Stem Pro 34-SFM medium, and the L-15 Leibovitz's medium for cultures in CO(2)
      free atmosphere were assessed. At day 5 of culture, total colony forming unit
      expansions of 14.44 +/- 3.74, 11.20 +/- 6.37, and 17.25 +/- 3.65-folds were
      attained, respectively. The expansion reached using L-15 medium in roller bottles
      was around 10 times higher than that achieved in the static control cultures. To
      our knowledge, this is the first report of cultures in CO(2)-free atmosphere to
      expand cord blood human hematopoietic stem cells and it opens a new branch of
      possibilities for culturing and clinical applications.

PMID- 20825281
TI  - Noninvasive repetitive imaging of somatostatin receptor 2 gene transfer with
      positron emission tomography.
AB  - Noninvasive in vivo imaging of gene expression is desirable to monitor gene
      transfer in both animal models and humans. Reporter transgenes with low
      endogenous expression levels are instrumental to this end. The human somatostatin
      receptor 2 (hSSTR2) has low expression levels in a variety of tissues, including
      muscle and liver. We tested the possibility of noninvasively and quantitatively
      monitoring hSSTR2 transgene expression, following adeno-associated viral (AAV)
      vector-mediated gene delivery to murine muscle and liver by positron emission
      tomography (PET) using (68)gallium-DOTA-Tyr(3)-Thr(8)-octreotate ((68)Ga
      DOTATATE) as a highly specific SSTR2 ligand. Repetitive PET imaging showed hSSTR2
      signal up to 6 months, which corresponds to the last time point of the analysis,
      after gene delivery in both transduced tissues. The levels of tracer accumulation
      measured in muscle and liver after gene delivery were significantly higher than
      in control tissues and correlated with the doses of AAV vector administered. As
      repetitive, quantitative, noninvasive imaging of AAV-mediated SSTR2 gene transfer
      to muscle and liver is feasible and efficient using PET, we propose this system
      to monitor the expression of therapeutic genes coexpressed with SSTR2.

PMID- 20825282
TI  - Retroviral and transposon-based tet-regulated all-in-one vectors with reduced
      background expression and improved dynamic range.
AB  - The regulated expression of therapeutic genes may become crucial in gene therapy
      when their constitutive expression interferes with cell fate in vivo. The
      efficient regulation of transgene expression requires tightly controlled
      inducible promoters, as shown for the tetracycline regulatory system (tet
      system). However, its application requires the introduction of two components
      into the target cell genome: the tet-responsive transactivator and the regulated
      expression cassette. In order to facilitate the usage of the tet-system for
      approaches in gene therapy, both components have to be transferred by a single
      vector, thus eliminating the preselection of transactivator positive cells.
      Published "all-in-one" vectors for regulated transgene expression display a
      relatively low signal-to-noise ratio, resulting in regulatory windows of around
      500-fold even in selected clones. In this study, we show that a modified vector
      architecture combined with the introduction of new tet-responsive promoters,
      Ptet, improved the dynamic range of such all-in-one vectors to levels up to
      14,000-fold for viral and 25,000-fold for nonviral transfer vectors in nonclonal
      human cell lines, and up to 2,800-fold in murine hematopoietic cell lines. This
      improved regulation was the result of a strong reduction of background expression
      in the off-state, even if cells were transduced at high multiplicity of
      infection, while induction remained at high levels. In addition, the results
      indicated that successful regulation of gene expression in different target cells
      depended on vector architecture as well as the choice of the Ptet-promoter.

PMID- 20825284
TI  - HIV-1-derived lentiviral vectors directly activate plasmacytoid dendritic cells,
      which in turn induce the maturation of myeloid dendritic cells.
AB  - Lentiviral vectors (LV) can induce type I interferon (IFN I) production from
      murine plasmacytoid dendritic cells (pDC), but not myeloid (my)DC. Here, we
      investigated whether this mechanism is conserved in human DC. MyDC and pDC were
      isolated from peripheral blood and transduced with increasing vector
      concentrations. Compared with in vitro differentiated monocyte-derived DC, the
      transduction efficiency of peripheral blood DC was low (ranging from <1% to 45%),
      with pDC showing the lowest susceptibility to LV transduction. Phenotype and
      function of myDC were not directly modified by LV transduction; by contrast, pDC
      produced significant levels of IFN-alpha and tumor necrosis factor-alpha. pDC
      activation was dependent on functional vector particles and was mediated by Toll
      like receptor 7/9 triggering. Coculture of myDC with pDC in the presence of LV
      resulted in myDC activation, with CD86 up-regulation and interleukin-6 secretion.
      These findings demonstrate that the induction of transgene-specific immunity is
      triggered by an innate immune response with pDC activation and consequent myDC
      maturation, a response that closely resembles the one induced by functional
      viruses. This information is important to design strategies aimed at using LV in
      humans for gene therapy, where adverse immune responses must be avoided, or for
      cancer immunotherapy, where inducing immunity is the goal.

PMID- 20825285
TI  - Amelioration of rat collagen-induced arthritis through CD4+ T cells apoptosis and
      synovial interleukin-17 reduction by indoleamine 2,3-dioxygenase gene therapy.
AB  - Indoleamine 2,3-dioxygenase (IDO) has been known as an emerging therapeutic
      target in autoimmunity-related arthritis. The treatment responses of adenoviral
      vectors encoding IDO (AdIDO) gene therapy in rat collagen-induced arthritis (CIA)
      were examined in this study. The therapeutic effects on ankle circumference,
      articular index, and radiographic and histological scores were evaluated in AdIDO
      injected ankle joints. We further determined CD4+ T-cell numbers and their
      apoptotic status, CD68(+) macrophage numbers, kynurenine (a downstream tryptophan
      metabolite) concentrations, interleukin-17 (IL-17) levels, and retinoic acid
      related orphan receptor gammat (RORgammat) expression in synovial tissues of CIA
      rats receiving AdIDO treatment. Reduction of ankle circumference, articular
      index, and radiographic and histological scores were noted in AdIDO-treated
      ankles, as compared with those receiving injection of control vectors.
      Furthermore, IDO gene transfer led to decreased infiltrating CD4+ T cells with
      enhanced apoptosis, reduced CD68+ macrophage numbers, increased kynurenine
      levels, lower IL-17 concentrations, and decreased RORgammat expression within the
      ankle joints. In addition, such a therapy diminished type II collagen-specific IL
      17 production and RORgammat expression in CD4+ T cells from draining lymph nodes
      of CIA rats. Our results demonstrate for the first time that intra-articular
      delivery of IDO gene ameliorated ankle arthritis of CIA rats by induction of CD4+
      T-cell apoptosis and reduction of synovial IL-17 production through the
      supplement of kynurenine. Taken together, these findings implicate the novel
      strategy of using IDO gene as a therapeutic approach in treating patients with
      rheumatoid arthritis.

PMID- 20825286
TI  - Vertebroplasty for adjacent vertebral fracture following lumbar interbody fusion.
AB  - PURPOSE: Adjacent segment vertebral compression fracture after lumbosacral
      instrumented fusion has been reported to be a significant complication. Recently,
      percutaneous vertebroplasty (PVP) has been widely used for the treatment of non
      traumatic osteoporotic vertebral fracture. However, the clinical effect of this
      minimally invasive treatment option to the post-fusion vertebral fracture has
      rarely been reported. We analysed characteristics of adjacent vertebral fractures
      following lumbar fusion and evaluated the clinical outcome of PVP. METHODS: A
      total of 202 consecutive patients underwent PVP for compression fracture in our
      institute between January 2007 and December 2008. Among them, nine symptomatic
      adjacent vertebral fractures following lumbar fusion were identified. We randomly
      selected 50 control patients undergoing vertebroplasty for osteoporotic
      compression fracture in single level. We analysed the clinical data according to
      age, height, body weight, body mass index (BMI), and bone mineral density (BMD).
      Clinical outcome was assessed by a visual analogue scale (VAS) score and the rate
      of overall satisfaction. RESULTS: Fractures occurred at the cranial adjacent
      vertebra after fusion surgery in all cases. The mean BMD score for the spine and
      femur were significantly higher than the control group (p < 0.05). After PVP, the
      mean VAS score improved from 8.1 to 3.2. The overall satisfaction rate was 88.9%.
      Other constitutional factors and clinical outcomes were similar to the control
      group. CONCLUSION: Adjacent vertebral fracture following lumbar fusion may occur
      as a kind of adjacent segment disease. The increased stress around the fusion
      segment can cause vertebral fracture even with a relatively higher BMD score.
      Vertebroplasty for the post-fusion vertebral fracture can be as effective as it
      is for the usual osteoporotic vertebral fracture.

PMID- 20825283
TI  - Genetic engineering of mesenchymal stem cells and its application in human
      disease therapy.
AB  - The use of stem cells for tissue regeneration and repair is advancing both at the
      bench and bedside. Stem cells isolated from bone marrow are currently being
      tested for their therapeutic potential in a variety of clinical conditions
      including cardiovascular injury, kidney failure, cancer, and neurological and
      bone disorders. Despite the advantages, stem cell therapy is still limited by low
      survival, engraftment, and homing to damage area as well as inefficiencies in
      differentiating into fully functional tissues. Genetic engineering of mesenchymal
      stem cells is being explored as a means to circumvent some of these problems.
      This review presents the current understanding of the use of genetically
      engineered mesenchymal stem cells in human disease therapy with emphasis on
      genetic modifications aimed to improve survival, homing, angiogenesis, and heart
      function after myocardial infarction. Advancements in other disease areas are
      also discussed.

PMID- 20825287
TI  - Management strategy for brain tumour diagnosed during pregnancy.
AB  - The occurrence of brain tumours during pregnancy is unusual, when this happen
      jeopardises the lives of both the mother and infant. This article aims at
      identifying the best medical management to be followed for a pregnant patient
      harbouring a brain tumour. The records of 10 patients with brain tumours
      diagnosed during pregnancy were retrospectively examined. The histological
      diagnosis revealed 3 grade 2 astrocytomas, and 1 grade 2 oligodendroglioma. All
      this gliomas (100%) developed dedifferentiation in the mean period of 27 months.
      The histology of the others tumours were 2 grade 1 meningiomas, 1 melanoma
      metastasis, 1 epidermoid tumour, 1 case of chemodectoma and 1 patient with a
      pituitary apoplexy in a non-function adenoma. There was no operative mortality in
      these series, and no fetal deaths were observed. Prior to craniotomy, five
      patients had caesarean sections, two others had vaginal deliveries. In three
      patients the delivery took place after the brain tumour treatment. Two patients
      had vaginal delivery and eight caesarean sections. The best moment to recommend
      the craniotomy and the neurosurgical removal of the tumour will depend of the
      mother's neurological condition, the tumour histological type as well as the
      gestational age. A multi-disciplinary approach was used to determine the optimal
      management for each patient.

PMID- 20825288
TI  - An unusual case of symptomatic Schwannoma on the elbow.
AB  - This case report regards a Schwannoma originating from the ulnar nerve at the
      elbow. It produced a variety of symptoms and severely impaired the patient's hand
      function. The surgical procedure consisted in the enucleation of the swelling and
      the anterior submuscular transposition of the ulnar nerve.

PMID- 20825289
TI  - Isolated cranio-spinal involvement of Rosai-Dorfman disease: case report.
AB  - Rosai-Dorfman disease is a rare non-neoplastic lymphoproliferative condition. It
      commonly affects individuals between third and fifth decades, most common
      presentation being in the form of massive painless cervical lymphadenopathy with
      fever, weight loss and malaise. Isolated intracranial involvement is rare seen in
      less than 5% of patients with extranodal involvement. We present a patient with
      isolated contiguous cranio-spinal involvement who presented to us with remitting
      symptoms.

PMID- 20825290
TI  - Refined analysis of complex language representations by non-invasive neuroimaging
      techniques.
AB  - OBJECTIVE: The determination of language lateralisation is important for patients
      with medically intractable epilepsy or a brain tumour near the language areas to
      avoid the risk of post-surgical language deficits. The aim of this study was to
      evaluate the clinical usefulness of near-infrared spectroscopy (NIRS) to identify
      language lateralisation compared with functional MRI (fMRI) and
      magnetoencephalography (MEG) in multiple language tasks. METHODS: We investigated
      28 patients whose language dominance was evaluated by the Wada test. fMRI, MEG
      and NIRS were performed to investigate language representation. All patients were
      asked to read three-letter words silently for fMRI and MEG (Kana reading) and to
      write words beginning with a visually presented letter (word generation) for
      NIRS. The laterality index was calculated to assess language lateralisation in
      each investigation. RESULTS: In 24 cases (85.7%), of which two investigations
      showed the same laterality, the results had perfect concordance with the Wada
      test. In patients with left dominance, the sensitivity and specificity of fMRI,
      MEG and NIRS was 95.0% and 62.5%, 100% and 87.5%, 75.0% and 87.5%, respectively.
      In three patients with right lateralization, only NIRS showed a significant
      increase of oxygenated-haemoglobin in the right inferior frontal region,
      indicating right dominance. CONCLUSION: We established a method to determine
      language lateralisation by co-utilising fMRI, MEG and NIRS with high reliability.
      NIRS recognised atypical language representation, in addition to fMRI and MEG.
      While fMRI, MEG and NIRS are not currently as accurate as the Wada test in
      determining language lateralisation, this non-invasive and repeatable method has
      great potential as an alternative to the Wada test in time following further
      research and refinement of these techniques.

PMID- 20825291
TI  - Pathological enlargement of midbrain Virchow-Robin spaces: a rare cause of
      obstructive hydrocephalus.
AB  - Midbrain multiloculated cystic formations can rarely origin by enlargement of
      Virchow-Robin spaces surrounding mesencephalo-thalamic artery and branches of the
      collicular and accessory collicular arteries. They can determine several pictures
      of midbrain syndrome and obstructive hydrocephalus. The authors describe a 38
      year-old man affected by a Benedikt's syndrome related to a midbrain multicystic
      formation. Clinical course, differential diagnosis, and therapeutic choice are
      here also briefly discussed.

PMID- 20825292
TI  - Intra-dural spinal arachnoid cysts: a short series of 10 patients.
AB  - OBJECTIVE: To describe intra-dural arachnoid cysts as the cause of compressive
      myelopathy. MATERIAL AND METHODS: A short series of 10 patients harbouring intra
      dural arachnoid cysts is described. A detailed description of symptomatology,
      radiological findings, surgical approach, techniques and outcome is discussed.
      Microsurgical excision was performed in all patients. In two patients, intra- and
      extra-spinal communications of cysts were found and were ligated. RESULTS: Good
      long-term results were achieved in all 10 patients, after surgical intervention.
      CONCLUSION: Rarely, intradural, extramedullary lesions like arachnoid cysts may
      lead on to compressive myelopathy causing spastic paraparesis. Except for the
      catastrophic complication like intra-cystic haemorrhage or subdural haematoma,
      the fatal complication is unlikely. The congenital dural defect is considered the
      cause behind the development of these cysts. Though uncommon, but intradural
      arachnoid cysts are important cause of compressive myelopathy. These lesions are
      curative, if excised surgically with precision.

PMID- 20825293
TI  - Haemorrhagic cerebellar fibrous histiocytoma: case report and literature review.
AB  - Malignant fibrous histiocytoma is uncommon within the central nervous system. It
      is a pleomorphic sarcoma originally found in soft tissue(1) and there are few
      reported cases within the central nervous system, in particular the cerebellum.
      This tumour is difficult to diagnose and may be difficult to treat. We present a
      case of cerebellar malignant fibrous histiocytoma, its management and literature
      review.

PMID- 20825296
TI  - Treatment of Graves' disease with antithyroid drugs: current perspectives.

PMID- 20825297
TI  - Time for thyrotropin releasing hormone to return to the United States of America.

PMID- 20825298
TI  - Biochemical changes during goiter induction by methylmercaptoimidazol and
      inhibition by delta-iodolactone in rat.
AB  - BACKGROUND: We have demonstrated that the administration of delta-iodolactone
      (i.e., 5-iodo-delta lactone) of arachidonic acid (IL-delta), a mediator in
      thyroid autoregulation, prevents goiter induction by methylmercaptoimidazol (MMI)
      in rats. Other studies have shown that transforming growth factor beta-1 (TGF
      beta1) mimics some of the actions of excess iodide, but its participation in
      autoregulation is disputed. The present studies were performed to test the
      hypotheses that IL-delta decreases thyroid growth by inhibition of cell
      proliferation and/or by stimulation of apoptosis due to oxidative stress, that
      TGF-beta is stimulated by an excess of iodide and by IL-delta, and that c-Myc and
      c-Fos expression are upregulated during goiter induction and downregulated during
      goiter inhibition. METHODS: Rats were treated with MMI alone or together with
      iodide or IL-delta. Thyroid weight, cell number, cell proliferation, apoptosis,
      and oxidative stress were determined. Proliferating cell nuclear antigen (PCNA),
      TGF-beta1, TGF-beta3, c-Myc, and c-Fos were measured by Western blot. RESULTS:
      MMI caused a progressive increase in thyroid weight accompanied by an increase in
      cell number, asymmetry of the ploidy histograms, and PCNA, c-Fos, and c-Myc
      expression. In addition, an early increase of apoptosis was observed. Peroxides
      as well as glutathione peroxidase and catalase activities were also increased in
      goitrous animals. The inhibitory action of IL-delta on goiter formation was
      accompanied by the inhibition of cell proliferation evidenced by a significant
      decrease in cell number, PCNA expression, and asymmetry of the ploidy histograms.
      A transient stimulation of apoptosis after 7 days of treatment was also observed.
      MMI administration stimulated TGF-beta1 but not TGF-beta3 synthesis. IL-delta
      alone caused a slight increase of TGF-beta3 but not TGF-beta1, whereas potassium
      iodide (KI) stimulated both isoforms and MMI reversed KI effect on TGF-beta1
      expression but not on TGF-beta3. CONCLUSIONS: The goiter inhibitory action of IL
      delta is due to the inhibition of cell proliferation and the transient
      stimulation of apoptosis. This latter action does not involve oxidative stress.
      TGF-beta1 does not play a role in the autoregulatory pathway mediated by IL
      delta. Iodide stimulates TGF-beta3 without the need of being organified. These
      results suggest that there may be more than one pathway involved in the
      autoregulatory mechanism.

PMID- 20825299
TI  - Burkitt-like lymphoma infiltrating a hyperfunctioning thyroid adenoma and
      presenting as a hot nodule.
AB  - BACKGROUND: Most solitary hyperfunctiong regions on thyroid scan consist of
      benign tissue. Here we report a patient with a Burkitt-like lymphoma that was
      infilterated into a region containing a hyperfunctioning nodule. SUMMARY: A 56
      year-old man was referred to our Endocrine Unit in May 2009 due to the incidental
      discovery of a large left thyroid lobe nodule by a computed tomography study.
      This had been performed to search for a primitive tumor in a patient with bone
      metastasis. He was clinically and biochemically thyrotoxic with no evidence of
      humoral thyroid autoimmunity. The nodule had a dyshomogenous appearance at neck
      ultrasonography, with multiple hypoechogenic areas and calcifications. (99m)
      Technetium thyroid scintiscan revealed a hot nodule with suppression of the
      contralateral lobe. Fine-needle aspiration cytology indicated the presence of
      neoplastic cells not of thyroid origin. Remission of hyperthyroidism was obtained
      with methimazole, and the patient was submitted to left lobe thyroidectomy and
      istmectomy. Histological analysis of the surgical specimen led to a diagnosis of
      Burkitt-like large B-cell lymphoma harbored within a thyroid adenoma. After
      further staging, the final diagnosis was stage IV E Burkitt-like lymphoma with
      the involvement of the bone and the thyroid. This is the first description of an
      aggressive Burkitt-like lymphoma that infiltrated an hyperfunctioning thyroid
      adenoma, thus presenting as a hot nodule at thyroid scintiscan. In our patient
      there was no humoral or histological evidence of thyroid autoimmunity, thus
      suggesting a metastatic seeding of the lymphoma within the hyperfunctioning
      thyroid nodule. CONCLUSIONS: Involvement of the thyroid gland by Burkitt-like
      lymphoma is extremely rare as is close localization of malignancy and a
      hyperfunctioning thyroid nodule. As highlighted by the present report, performing
      fine-needle aspiration cytology should be always considered in the clinical
      context of a metastatic disease of unknown origin or when there are
      ultrasonography signs suggesting malignancy, even when the nodule is
      hyperfunctioning.

PMID- 20825300
TI  - Lethal, malignant, metastatic struma ovarii.
AB  - BACKGROUND: Struma ovarii (SO) is extremely rare, with less than 200 reported
      cases in the medical literature. SO is defined by the presence of an ovarian
      tumor containing thyroid tissue as the predominant cell type. Malignant
      transformation is rare and lethal cases of SO are even rarer. We report on a
      patient presenting with left ovarian cystic SO and lethal outcome. SUMMARY: A 45
      year-old woman was diagnosed with a follicular variant of papillary carcinoma on
      laparotomy and left salpingo-oophorectomy. She had persistently elevated serum
      thyroglobulin following total thyroidectomy + radioiodine and second-look
      surgery. Imaging scan analysis showed pelvic tumor recurrence and hypervascular
      liver metastases during follow-up as well as peritoneal carcinomatosis in the
      pelvis, right abdominal wall, and malignant ascites. The patient died from
      cachexia at 37 months after diagnosis. CONCLUSIONS: Such an aggressive malignant
      disease and lethal course of SO is rare. Total thyroidectomy is mandatory to
      exclude a primary thyroid neoplasm and for radioiodine therapy and follow-up. SO
      may spread to contralateral ovary, pelvic nodes, peritoneum, liver, lungs, and
      bones through hematogeneous spread, which is different from the dissemination
      pattern of papillary thyroid carcinomas. Imaging highlights the mixed behavior of
      this ovarian tumor.

PMID- 20825301
TI  - Bilateral Killian-Jamieson diverticula incidentally found on thyroid
      ultrasonography.
AB  - BACKGROUND: Killian-Jamieson diverticulum (KJD) is a rare esophageal diverticulum
      that protrudes through the muscular gap in the anterolateral wall of the proximal
      cervical esophagus inferior to the cricopharyngeus. Although several patients
      with bilateral KJD have been reported, high-resolution ultrasound (US) image of
      bilateral KJD has never been reported. SUMMARY: A 71-year-old man visited our
      hospital for annual follow-up of known thyroid nodules. In addition to the
      previously noted thyroid nodules, two arc-shaped hyperechoic lesions with
      reverberation artifacts, which suggested air-containing lesions, were
      unexpectedly seen posterior to bilateral thyroid lobes. Although the connection
      between the esophagus and the lesions was not definitely visible on US, our first
      differential diagnosis was esophageal diverticula. They were confirmed to be
      bilateral KJD on the following pharyngoesophagography. CONCLUSIONS: If US
      features are not enough to differentiate esophageal diverticulum from suspicious
      thyroid nodule, pharyngoesophagography can be performed instead of invasive fine
      needle aspiration to obtain a definite diagnosis of incidentally detected
      esophageal diverticulum.

PMID- 20825302
TI  - Sorafenib-induced destructive thyroiditis.

PMID- 20825305
TI  - Cancer as a cause of death among people with AIDS in the United States.
AB  - BACKGROUND: People with human immunodeficiency virus (HIV) infection and AIDS
      have an elevated risk for cancer. Highly active antiretroviral therapy (HAART),
      which has been widely available since 1996, has resulted in dramatic decreases in
      AIDS-related deaths. METHODS: We evaluated cancer as a cause of death in a US
      registry-based cohort of 83,282 people with AIDS (1980-2006). Causes of death due
      to AIDS-defining cancers (ADCs) and non-ADCs (NADCs) were assessed. We evaluated
      mortality rates and the fraction of deaths due to cancer. Poisson regression
      assessed rates according to calendar year of AIDS onset. RESULTS: Overall
      mortality decreased from 302 deaths per 1000 person-years in 1980-1989, to 140
      deaths per 1000 person-years in 1990-1995, and to 29 deaths per 1000 person-years
      in 1996-2006. ADC-related mortality decreased from 2.95 deaths per 1000 person
      years in 1980-1989 to 0.65 deaths per 1000 person-years in 1996-2006 (P < .01),
      but the fraction of ADC-related deaths increased from 1.05% to 2.47% in
      association with decreases in other AIDS-related deaths. Non-Hodgkin lymphoma was
      the most common cancer-related cause of death (36% of deaths during 1996-2006).
      Likewise, NADC-related mortality decreased from 2.21 to 0.84 deaths per 1000
      person-years from the period 1980-1989 to the period 1996-2006 (P < .05), but the
      fraction of NADC-deaths increased to 3.16% during 1996-2006. Lung cancer was the
      most common NADC cause of death (21% of cancer-related deaths in 1996-2006).
      CONCLUSIONS: Cancer-related mortality decreased in the HAART era, but because of
      decreasing mortality due to AIDS, cancers account for a growing fraction of
      deaths. Improved cancer prevention and treatment, particularly for non-Hodgkin
      lymphoma and lung cancer, would reduce mortality among people with AIDS.

PMID- 20825307
TI  - When diarrhea gets deadly: a look at gastroenteritis outbreaks in nursing homes.

PMID- 20825308
TI  - Surveillance for outbreaks of gastroenteritis in long-term care facilities,
      Australia, 2002-2008.
AB  - BACKGROUND: Each year in Australia, health departments investigate hundreds of
      gastroenteritis outbreaks. Long-term care facilities (LTCFs) for elderly persons
      are a common setting for these outbreaks and can result in potentially serious
      outcomes. METHODS: We established surveillance for gastroenteritis outbreaks in
      2001, and analyzed data on outbreaks occurring from 1 July 2002 through 30 June
      2008 to estimate the incidence in Australian LTCFs and residents. We summarized
      outbreaks by mode of transmission and etiological agent. We used negative
      binomial regression to examine variation in the number of fecal specimens
      collected in outbreaks-a marker of investigation intensity. RESULTS: During
      surveillance, 3257 (52%) of 6295 outbreaks of gastroenteritis and foodborne
      disease in Australia were reported in LTCFs. These outbreaks affected 84,769
      people, with 1577 people hospitalized and 209 deaths. There were 0.19 (95%
      confidence interval, 0.14-0.26) residents affected per 1000 bed days and 16.8
      (95% confidence interval, 12.4-22.7) outbreaks per 100 LTCFs annually. LTCF
      outbreaks were most commonly transmitted from person to person. Only 43 (1.3% )
      of 3257 outbreaks were foodborne, although 47 (6.4%) of 733 residents were
      hospitalized and 20 (2.7%) of 733 died. Norovirus was responsible for 1136 (35%)
      of all 3257 outbreaks. Higher numbers of fecal specimens per outbreak were
      collected in 4 Australian States, in later years of surveillance, and where the
      etiology was identified. CONCLUSIONS: Norovirus outbreaks spread from person to
      person are common in LTCFs, although clinicians should be alert for foodborne
      outbreaks with more serious consequences. There is a need to identify effective
      infection control measures to assist facilities in managing outbreaks of
      gastroenteritis.

PMID- 20825309
TI  - Jarisch-Herxheimer reaction after penicillin therapy among patients with syphilis
      in the era of the hiv infection epidemic: incidence and risk factors.
AB  - The incidence of and risk factors for Jarisch-Herxheimer (JH) reaction were
      investigated prospectively among 240 human immunodeficiency virus (HIV)-infected
      and 115 HIV-uninfected patients with syphilis who received penicillin treatment.
      The overall rate of JH reaction was 31.5% (34.6% in HIV-infected patients and
      25.2% in HIV-uninfected patients). In multivariate analysis, risk factors for JH
      reaction included high rapid plasma reagin (RPR) titers (per log(2) RPR increase,
      risk ratio [RR], 1.19; 95% confidence interval [CI], 1.04-1.37), early syphilis
      (RR, 8.59; 95% CI, 4.75-15.56), and prior penicillin treatment (RR, 0.39; 95% CI,
      0.20-0.78).

PMID- 20825310
TI  - Screening student athletes for sickle cell trait--a social and clinical
      experiment.

PMID- 20825311
TI  - Patient safety beyond the hospital.

PMID- 20825306
TI  - Excess mortality in patients with AIDS in the era of highly active antiretroviral
      therapy: temporal changes and risk factors.
AB  - BACKGROUND: Excess mortality has decreased among human immunodeficiency virus
      (HIV)-infected patients but without evidence of a decrease among patients with
      AIDS. We assessed temporal changes in excess mortality and elucidated risk
      factors for excess mortality in patients with AIDS diagnosed in the era of highly
      active antiretroviral therapy (HAART). METHODS: We included 1188 patients of the
      Longitudinal Study of Ocular Complications in AIDS who were aged 25-64 years at
      enrollment and who received a diagnosis of AIDS after 1995. We calculated excess
      mortality as the age-, year-, and sex-adjusted difference in mortality rates
      between patients with AIDS and persons in the US general population during the
      period 1999-2007. We used a relative survival model to identify risk factors for
      excess mortality. RESULTS: There were a mean of 50 excess deaths per 1000 person
      years (95% confidence interval [CI], 44-57 excess deaths per 1000 person-years)
      during 1999-2007. Excess mortality almost halved, with an annual decrease of 8.0%
      per year (95% CI, 3.0%-12.7%; P = .002) but remained high at 36 excess deaths per
      1000 person-years in 2007. Viral load >400 copies/mL (compared with <or= 400
      copies/mL; risk ratio, 3.4; 95% CI, 2.3-5.0), CD4(+) count <200 cells/MUL
      (compared with >or= 200 cells/MUL; risk ratio, 2.7; 95% CI, 1.9-3.9), and
      cytomegalovirus retinitis (risk ratio, 1.6; 95% CI, 1.2-2.1) were the strongest
      risk factors for excess mortality. CONCLUSIONS: Excess mortality among patients
      with AIDS was nearly halved in the HAART era and most strongly linked to stage of
      HIV disease. These results reflect the continuing improvements in AIDS management
      but also highlight that excess mortality remains ~5 times higher in patients with
      AIDS than in HIV-infected patients without AIDS.

PMID- 20825313
TI  - Rapid molecular detection of tuberculosis and rifampin resistance.
AB  - BACKGROUND: Global control of tuberculosis is hampered by slow, insensitive
      diagnostic methods, particularly for the detection of drug-resistant forms and in
      patients with human immunodeficiency virus infection. Early detection is
      essential to reduce the death rate and interrupt transmission, but the complexity
      and infrastructure needs of sensitive methods limit their accessibility and
      effect. METHODS: We assessed the performance of Xpert MTB/RIF, an automated
      molecular test for Mycobacterium tuberculosis (MTB) and resistance to rifampin
      (RIF), with fully integrated sample processing in 1730 patients with suspected
      drug-sensitive or multidrug-resistant pulmonary tuberculosis. Eligible patients
      in Peru, Azerbaijan, South Africa, and India provided three sputum specimens
      each. Two specimens were processed with N-acetyl-L-cysteine and sodium hydroxide
      before microscopy, solid and liquid culture, and the MTB/RIF test, and one
      specimen was used for direct testing with microscopy and the MTB/RIF test.
      RESULTS: Among culture-positive patients, a single, direct MTB/RIF test
      identified 551 of 561 patients with smear-positive tuberculosis (98.2%) and 124
      of 171 with smear-negative tuberculosis (72.5%). The test was specific in 604 of
      609 patients without tuberculosis (99.2%). Among patients with smear-negative,
      culture-positive tuberculosis, the addition of a second MTB/RIF test increased
      sensitivity by 12.6 percentage points and a third by 5.1 percentage points, to a
      total of 90.2%. As compared with phenotypic drug-susceptibility testing, MTB/RIF
      testing correctly identified 200 of 205 patients (97.6%) with rifampin-resistant
      bacteria and 504 of 514 (98.1%) with rifampin-sensitive bacteria. Sequencing
      resolved all but two cases in favor of the MTB/RIF assay. CONCLUSIONS: The
      MTB/RIF test provided sensitive detection of tuberculosis and rifampin resistance
      directly from untreated sputum in less than 2 hours with minimal hands-on time.
      (Funded by the Foundation for Innovative New Diagnostics.)

PMID- 20825314
TI  - E2-2 protein and Fuchs's corneal dystrophy.
AB  - BACKGROUND: Fuchs's corneal dystrophy (FCD) is a leading cause of corneal
      transplantation and affects 5% of persons in the United States who are over the
      age of 40 years. Clinically visible deposits called guttae develop under the
      corneal endothelium in patients with FCD. A loss of endothelial cells and
      deposition of an abnormal extracellular matrix are observed microscopically. In
      advanced disease, the cornea swells and becomes cloudy because the remaining
      endothelial cells are not sufficient to keep the cornea dehydrated and clear.
      Although rare genetic variation that contributes to both early-onset and typical
      late-onset forms of FCD has been identified, to our knowledge, no common variants
      have been reported. METHODS: We performed a genomewide association study and
      replicated the most significant observations in a second, independent group of
      subjects. RESULTS: Alleles in the transcription factor 4 gene (TCF4), encoding a
      member of the E-protein family (E2-2), were associated with typical FCD
      (P=2.3x10(-26)). The association increased the odds of having FCD by a factor of
      30 for persons with two copies of the disease variants (homozygotes) and
      discriminated between case subjects and control subjects with about 76% accuracy.
      At least two regions of the TCF4 locus were associated independently with FCD.
      Alleles in the gene encoding protein tyrosine phosphatase receptor type G (PTPRG)
      were associated with FCD (P=4.0x10(-7)), but the association did not reach
      genomewide significance. CONCLUSIONS: Genetic variation in TCF4 contributes to
      the development of FCD. (Funded by the National Eye Institute and others.)

PMID- 20825315
TI  - Persistent malignant stem cells in del(5q) myelodysplasia in remission.
AB  - BACKGROUND: The in vivo clinical significance of malignant stem cells remains
      unclear. METHODS: Patients who have the 5q deletion (del[5q]) myelodysplastic
      syndrome (interstitial deletions involving the long arm of chromosome 5) have
      complete clinical and cytogenetic remissions in response to lenalidomide
      treatment, but they often have relapse. To determine whether the persistence of
      rare but distinct malignant stem cells accounts for such relapses, we examined
      bone marrow specimens obtained from seven patients with the del(5q)
      myelodysplastic syndrome who became transfusion-independent while receiving
      lenalidomide treatment and entered cytogenetic remission. RESULTS: Virtually all
      CD34+, CD38+ progenitor cells and stem cells that were positive for CD34 and
      CD90, with undetectable or low CD38 (CD38-/low), had the 5q deletion before
      treatment. Although lenalidomide efficiently reduced these progenitors in
      patients in complete remission, a larger fraction of the minor, quiescent,
      CD34+,CD38-/low, CD90+ del(5q) stem cells as well as functionally defined del(5q)
      stem cells remained distinctly resistant to lenalidomide. Over time, lenalidomide
      resistance developed in most of the patients in partial and complete remission,
      with recurrence or expansion of the del(5q) clone and clinical and cytogenetic
      progression. CONCLUSIONS: In these patients with the del(5q) myelodysplastic
      syndrome, we identified rare and phenotypically distinct del(5q) myelodysplastic
      syndrome stem cells that were also selectively resistant to therapeutic targeting
      at the time of complete clinical and cytogenetic remission. (Funded by the
      EuroCancerStemCell Consortium and others.)

PMID- 20825317
TI  - MDR tuberculosis--critical steps for prevention and control.

PMID- 20825316
TI  - Gentamicin-collagen sponge for infection prophylaxis in colorectal surgery.
AB  - BACKGROUND: Despite the routine use of prophylactic systemic antibiotics,
      surgical-site infection continues to be associated with significant morbidity and
      cost after colorectal surgery. The gentamicin-collagen sponge, an implantable
      topical antibiotic agent, is approved for surgical implantation in 54 countries.
      Since 1985, more than 1 million patients have been treated with the sponges.
      METHODS: In a phase 3 trial, we randomly assigned 602 patients undergoing open or
      laparoscopically assisted colorectal surgery at 39 U.S. sites to undergo either
      the insertion of two gentamicin-collagen sponges above the fascia at the time of
      surgical closure (the sponge group) or no intervention (the control group). All
      patients received standard care, including prophylactic systemic antibiotics. The
      primary end point was surgical-site infection occurring within 60 days after
      surgery, as adjudicated by a clinical-events classification committee that was
      unaware of the study-group assignments. RESULTS: The incidence of surgical-site
      infection was higher in the sponge group (90 of 300 patients [30.0%]) than in the
      control group (63 of 302 patients [20.9%], P=0.01). Superficial surgical-site
      infection occurred in 20.3% of patients in the sponge group and 13.6% of patients
      in the control group (P=0.03), and deep surgical-site infection in 8.3% and 6.0%
      (P=0.26), respectively. Patients in the sponge group were more likely to visit an
      emergency room or surgeon's office owing to a wound-related sign or symptom
      (19.7%, vs. 11.0% in the control group; P=0.004) and to be rehospitalized for
      surgical-site infection (7.0% vs. 4.3%, P=0.15). The frequency of adverse events
      did not differ significantly between the two groups. CONCLUSIONS: Our large,
      multicenter trial shows that the gentamicin-collagen sponge is not effective at
      preventing surgical-site infection in patients who undergo colorectal surgery;
      paradoxically, it appears to result in significantly more surgical-site
      infections. (Funded by Innocoll Technologies; ClinicalTrials.gov number,
      NCT00600925.)

PMID- 20825318
TI  - Images in clinical medicine. Miliary tuberculosis.

PMID- 20825319
TI  - Case records of the Massachusetts General Hospital. Case 27-2010. A 73-year-old
      woman with chronic anemia.

PMID- 20825320
TI  - Tuberculosis diagnosis--time for a game change.

PMID- 20825321
TI  - Major progress in Fuchs's corneal dystrophy.

PMID- 20825322
TI  - Lessons from the mammography wars.

PMID- 20825323
TI  - Basophils and nephritis in lupus.

PMID- 20825324
TI  - Bisphosphonates and atypical femoral fractures.

PMID- 20825325
TI  - Infliximab, azathioprine, or combination therapy for Crohn's disease.

PMID- 20825326
TI  - Syphilis and social upheaval in China.

PMID- 20825327
TI  - Retinal injuries from a handheld laser pointer.

PMID- 20825328
TI  - Kidney paired donation in live-donor kidney transplantation.

PMID- 20825333
TI  - Expanding practitioner scopes of practice during public health emergencies:
      experiences from the 2009 H1N1 pandemic vaccination efforts.
AB  - In a public health emergency involving significant surges in patients and
      shortages of medical staff, supplies, and space, temporarily expanding scopes of
      practice of certain healthcare practitioners may help to address heightened
      population health needs. Scopes of practice, which are defined by state practice
      acts, set forth the range of services that licensed practitioners are authorized
      to perform. The U.S. has had limited experience with temporarily expanding scopes
      of practice during emergencies. However, during the 2009 H1N1 pandemic response,
      many states took some form of action to expand the practice scopes of certain
      categories of practitioners in order to authorize them to administer the pandemic
      vaccine. No standard legal approach for expanding scopes of practice during
      emergencies exists across states, and scope of practice expansions during
      routine, nonemergency times have been the subject of professional society debate
      and legal action. These issues raise the question of how states could effectively
      implement expansions for health services beyond administering vaccine and ensure
      consistency in expansions across states during catastrophic events that require a
      shift to crisis standards of care. This article provides an overview of scopes of
      practice, a summary of the range of legal and regulatory approaches used in the
      U.S. to expand practice scopes for vaccination during the 2009 H1N1 response, and
      recommendations for future research.

PMID- 20825334
TI  - Response to H1N1 in a U.S.-Mexico border community.
AB  - Public health experts from a county health department and a school of public
      health collaborated to establish a simple, functional surveillance system to
      monitor swine-origin influenza virus as it crossed from Mexico into a Texas
      border community during the 2009 pandemic. The draft national and state
      preparedness plans were found to be cumbersome at the local level, so a simple,
      more practical real-time surveillance and response system was developed, in part
      by modifying these documents, and immediately implemented. Daily data analyses,
      including geographical information system mapping of cases and reports of school
      and daycare absences, were used for outbreak management. Aggregate reports of
      influenzalike illness and primary school absences were accurate in predicting
      influenza activity and were practical for use in local tracking, making
      decisions, and targeting interventions. These simple methods should be considered
      for local implementation and for integration into national recommendations for
      epidemic preparedness and response.

PMID- 20825335
TI  - Stigma, health disparities, and the 2009 H1N1 influenza pandemic: how to protect
      Latino farmworkers in future health emergencies.
AB  - At the outset of the 2009 H1N1 influenza ("swine flu") pandemic, Mexican
      nationals and Mexican commodities were shunned globally, and, in the United
      States, some media personalities characterized Mexican immigrants as disease
      vectors who were a danger to the country. We investigated instances in the U.S.
      of stigmatization of Latino migrant and seasonal farmworkers (MSFWs) and
      developed guidance for officials in curtailing its effects. At the same time, we
      explored social factors that make farmworkers more vulnerable to influenza
      infection and its complications, including high rates of underlying medical
      conditions, limited access to health care, and certain circumstances that
      interfere with the ability to implement community mitigation measures. This
      article reviews study findings and concludes with advice to policymakers and
      practitioners on the need to mitigate stigmatization in future outbreaks, to
      create public health preparedness systems that better protect migrant and
      seasonal farmworkers, and to undertake larger reforms to reduce institutional
      conditions that render farmworkers at greater risk for morbidity and mortality
      during health emergencies.

PMID- 20825336
TI  - Public compliance with mass prophylaxis guidance.
AB  - In 2008, the New York City Department of Health and Mental Hygiene (NYC DOHMH)
      conducted a series of 8 focus groups to determine what improvements could be made
      to existing plans to ensure that the public would adhere to instructions issued
      during an emergency that required mass antibiotic distribution following an
      aerosolized anthrax attack. Discussion focused on perceptions surrounding public
      health emergencies, overall point-of dispensing (POD) strategy, willingness to
      pick up medications for others, and additional information that participants
      would need before and during an emergency. Participation in each group ranged
      from 7 to 10 members. Most participants indicated a willingness to actively
      participate in emergency response and to follow directions issued by authorities.
      Some said they would wait to see how others reacted to medication being provided
      before taking theirs. Participants expressed a universal desire for education on
      both dispensing plans and diseases before an incident occurs. They expressed
      concerns about anxiety levels among the public and maintaining adequate security
      at dispensing sites, though they felt that NYC's plans were generally realistic.
      The most trusted sources identified to disseminate information were the mayor,
      the city health commissioner, and a local cable news channel. While many
      participants indicated they would use the internet to find information during an
      emergency, multiple delivery methods must be used to ensure the broadest reach
      within the community, as not everyone has internet access. Health authorities
      must partner with the public before, during, and after an emergency to achieve
      the best possible outcomes from a response effort that relies greatly on public
      cooperation.

PMID- 20825337
TI  - The Medical Reserve Corps as part of the federal medical and public health
      response in disaster settings.
AB  - The Secretary of the Department of Health and Human Services (HHS), through the
      Office of the Assistant Secretary for Preparedness and Response (ASPR),
      coordinates federal Emergency Support Function (ESF) #8 preparedness, response,
      and recovery actions. To address these needs, the ASPR can draw on trained
      personnel from a variety of sources, both from within and outside HHS. Among the
      resources under the domain of HHS is the Medical Reserve Corps (MRC), directed by
      the Office of the Civilian Volunteer Medical Reserve Corps (OCVMRC) in the Office
      of the Surgeon General. MRC units are community based and function as a way to
      locally organize and utilize medical and public health professionals, such as
      physicians, nurses, pharmacists, dentists, veterinarians, and epidemiologists.
      Nonclinical volunteers, such as interpreters, chaplains, office workers, legal
      advisors, and others, can fill logistical and support roles in MRC units. This
      article discusses locally controlled (Hurricanes Gustav and Ike) and federalized
      (Hurricanes Katrina and Rita) MRC activations, and it describes the advantages of
      using medical volunteers in a large-scale disaster response setting.

PMID- 20825338
TI  - Building public health capacity in Afghanistan to implement the International
      Health Regulations: a role for security forces.
AB  - The government of Afghanistan, with international partners and donors, has
      achieved substantial public health improvements during the past 8 years. But a
      critical gap remains: capacities to detect and respond to disease outbreaks that
      could constitute a public health emergency of international concern, as required
      by the International Health Regulations (IHR). The Afghan Ministry of Public
      Health seeks to build these capacities, but conflict and scarcity of resources
      hinder public health surveillance and response, diagnostic laboratory and
      clinical management capacity is limited, and massive international population
      movements could permit outbreaks to cross international borders. Several diseases
      covered by the IHR, such as polio, are endemic in Afghanistan, and risk of novel
      disease emergence may be elevated in some areas. The security forces of the
      United States and other countries with military presence in Afghanistan are
      potential partners for the government of Afghanistan in strengthening the public
      health capacity. They could extend specialized disease surveillance and response
      capabilities to the Afghan military and civilian sectors and could integrate
      surveillance and response capacity building into ongoing development programs,
      especially in insecure areas. The World Health Organization could provide the
      forum for coordinating military and civilian contributions to public health
      capacity strengthening in Afghanistan and could help ensure that international
      health sector development efforts address Afghan public health priorities in
      addition to IHR requirements.

PMID- 20825339
TI  - Preparing to save lives and recover after a nuclear detonation: implications for
      U.S. policy.

PMID- 20825340
TI  - Symptomatic asymmetry in very young infants: a Delphi study on the development of
      a screening instrument.
AB  - The objective of this study was to develop a screening instrument for pediatric
      physiotherapists to distinguish a symptomatic asymmetry in the clinical
      evaluation of young infants (age <6 months) with an asymmetric head posture. We
      chose two consensus methods, a two-round Delphi design and an expert meeting
      using nominal group technique, for reaching agreement about classification of
      diagnoses and clinical diagnostic criteria (CDC). Seventeen diagnoses with an
      expression of asymmetry with 69 matching CDC were assessed. In two Delphi rounds,
      six medical specialists and seven pediatric physiotherapists were polled
      anonymously on the classification, completeness, and relevance of the diagnoses
      and the CDC. Panel consistency in round 2, expressed as Cronbach's-alpha, was
      0.89. In round 3, a face-to-face meeting with eight therapists, the previously
      selected diagnoses and CDC were prioritised, reduced to 10 diagnoses and 21 CDC,
      and completed with eight hard clinical signs (red flags). Finally, a differential
      diagnostic screening instrument, containing a classification scheme, the CDC for
      differential diagnostics, and a list of "red flags" was established on the basis
      of literature search and expert consensus. Cross-validity and reliability of the
      instrument will be investigated in future research.

PMID- 20825341
TI  - Systemic hemodynamics in young adults with the metabolic syndrome: the
      Cardiovascular Risk in Young Finns Study.
AB  - OBJECTIVE: We conducted the present study to examine associations of three
      different metabolic syndrome (MetS) definitions and their components to arterial
      stiffness, systemic vascular resistance, and left ventricular function at
      population level. In addition, the objective of the study was to examine
      associations of spontaneous recovery from MetS over 6 years' follow-up to
      systemic hemodynamics. METHODS: The study population consisted of 1,741 Finnish
      young adults (aged 30-45 years) who had complete MetS risk factor and hemodynamic
      data available at 2007. Associations of spontaneous recovery from MetS to
      systemic hemodynamics was studied on a subpopulation of 1,391 subjects who had
      also complete MetS risk factor data available at 2001. Hemodynamic measurements
      were performed using a whole-body impedance cardiography device. RESULTS: MetS
      and increasing number of MetS components were associated with lower stroke index
      (P < 0.001) and higher systemic vascular resistance index (P < 0.005) and
      arterial pulse wave velocity (P < 0.005). In MetS persistent group, stroke index
      was lower (P = 0.024), and pulse wave velocity was higher (P = 0.003) compared to
      MetS recovery group. CONCLUSION: All current MetS definitions identify young
      adults with altered systemic hemodynamics, and recovery from MetS is associated
      with a favorable hemodynamic profile.

PMID- 20825342
TI  - Functioning and disability in migraine.
AB  - OBJECTIVE: To describe functioning and disability in patients with migraine
      according to the model endorsed by the International Classification of
      Functioning Disability and Health (ICF). DESIGN: Adult patients with migraine
      were consecutively enrolled. The Migraine Disability Assessment score (MIDAS),
      the ICF checklist and the WHO Disability Assessment Schedule II (WHO-DAS II) were
      administered in individual sessions. Descriptive analyses were performed to
      report on MIDAS and WHO-DAS II scores. ICF categories reported as a problem by
      more than 20% of patients were described in detail. RESULTS: One hundred two
      patients (mean age 43.5; 85.3% females) were enrolled. Mean MIDAS score was 28.2.
      WHO-DAS II was 18.7, and the most severe limitations are reported in life
      activities and in participation to social situations. A total of 61 ICF
      categories reached the threshold of 20%, 19 Body Functions and Structures, 25
      Activities and Participation and 17 Environmental Factors. CONCLUSIONS: We
      reported information on a broad set of domains, expanding migraine-specific ones,
      such as pain and lost workdays that were previously reported in other studies.
      Our results enable to enlarge the perspective of disability in patients with
      migraine, considering both symptoms, activities and the role of environmental
      factors.

PMID- 20825343
TI  - Functioning and disability in Parkinson's disease.
AB  - OBJECTIVE: To describe functioning and disability of patients with Parkinson's
      Disease (PD) according to the model endorsed by the International Classification
      of Functioning Disability and Health (ICF). DESIGN: Adult PD patients were
      consecutively enrolled. The ICF checklist and the WHO Disability Assessment
      Schedule II (WHO-DAS II) were administered in individual sessions. Hoehn and Yahr
      Staging (HY) was used to define PD severity. Descriptive analyses have been
      performed to report on HY and WHO-DAS II scores. ICF categories reported as a
      problem by more than 20% of patients are described in detail. RESULTS: Ninety-six
      patients with PD (mean age 64.1, 33.3% females) were enrolled, 48.4% of them were
      in HY class 2. WHO-DAS II mean score was 18.1 and the most severe limitations are
      reported in getting around and in participation to social situations. A total of
      71 ICF categories reached the threshold of 20%, mostly derived from Activities
      and Participation domain. CONCLUSIONS: We reported information on a broad set of
      domains, expanding those PD-specific, such as reduced mobility. Our results are
      useful to define what dimensions have to be considered to expand disability
      assessment in patients with PD, considering both symptoms, activities and the
      role of environmental factors.

PMID- 20825344
TI  - Basis of virulence in community-associated methicillin-resistant Staphylococcus
      aureus.
AB  - Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)
      strains are causing a severe pandemic of mainly skin and soft tissue and
      occasionally fatal infections. The basis of their success is the combination of
      methicillin resistance at low fitness cost and high virulence. Investigation of
      the virulence potential of CA-MRSA, a key prerequisite for the development of
      anti-CA-MRSA therapeutics, has focused on strain USA300, which is responsible for
      the most serious CA-MRSA epidemic seen in the United States. Current data
      indicate that in this strain virulence evolved via increased expression of core
      genome-encoded virulence determinants, such as alpha-toxin and phenol-soluble
      modulins, and acquisition of the phage-encoded Panton-Valentine leukocidin (PVL)
      genes. All these toxins impact disease progression in animal models of USA300
      infection. In contrast, the basis of virulence in other CA-MRSA epidemics, which
      also include PVL-negative strains, is poorly understood.

PMID- 20825345
TI  - Biological functions and biogenesis of secreted bacterial outer membrane
      vesicles.
AB  - Gram-negative bacteria produce outer membrane vesicles (OMVs) that contain
      biologically active proteins and perform diverse biological processes. Unlike
      other secretion mechanisms, OMVs enable bacteria to secrete insoluble molecules
      in addition to and in complex with soluble material. OMVs allow enzymes to reach
      distant targets in a concentrated, protected, and targeted form. OMVs also play
      roles in bacterial survival: Their production is a bacterial stress response and
      important for nutrient acquisition, biofilm development, and pathogenesis. Key
      characteristics of OMV biogenesis include outward bulging of areas lacking
      membrane-peptidoglycan bonds, the capacity to upregulate vesicle production
      without also losing outer membrane integrity, enrichment or exclusion of certain
      proteins and lipids, and membrane fission without direct energy from ATP/GTP
      hydrolysis. Comparisons of similar budding mechanisms from diverse biological
      domains have provided new insight into evaluating mechanisms for outer membrane
      vesiculation.

PMID- 20825346
TI  - Intracellular lifestyles and immune evasion strategies of uropathogenic
      Escherichia coli.
AB  - Paradigms in the pathogenesis of urinary tract infections have shifted
      dramatically as a result of recent scientific revelations. Beyond extracellular
      colonization of the bladder luminal surface, as traditional clinical thinking
      would hold, uropathogenic bacteria direct a complex, intracellular cascade that
      shelters bacteria from host defenses and leads to persistent bacterial residence
      within the epithelium. After epithelial invasion, many organisms are promptly
      expelled by bladder epithelial cells; a minority establish a niche in the
      cytoplasm that results in the development of biofilm-like intracellular bacterial
      communities and serves as the primary location for bacterial expansion.
      Exfoliation of the superficial epithelial layer acts to reduce the bacterial load
      but facilitates chronic residence of small nests of bacteria that later reemerge
      to cause some episodes of recurrent cystitis, a familiar clinical scenario in
      otherwise healthy women. Advances in both in vitro and animal models of cystitis
      promise to provide insights into the bacterial and host transcriptional and
      biochemical pathways that define these pathogenic stages.

PMID- 20825348
TI  - Organelle-like membrane compartmentalization of positive-strand RNA virus
      replication factories.
AB  - Positive-strand RNA virus genome replication is invariably associated with
      extensively rearranged intracellular membranes. Recent biochemical and electron
      microscopy analyses, including three-dimensional electron microscope tomographic
      imaging, have fundamentally advanced our understanding of the ultrastructure and
      function of organelle-like RNA replication factories. Notably, for a range of
      positive-strand RNA viruses embodying many major differences, independent studies
      have revealed multiple common principles. These principles include that RNA
      replication often occurs inside numerous virus-induced vesicles invaginated or
      otherwise elaborated from a continuous, often endoplasmic reticulum-derived
      membrane network. Where analyzed, each such vesicle typically contains only one
      or a few genome replication intermediates in conjunction with many copies of
      viral nonstructural proteins. In addition, these genome replication compartments
      often are closely associated with sites of virion assembly and budding. Our
      understanding of these complexes is growing, providing substantial new insights
      into the organization, coordination, and potential control of crucial processes
      in virus replication.

PMID- 20825349
TI  - Noise and robustness in prokaryotic regulatory networks.
AB  - Robustness is the quality of any relational object (biological or otherwise) to
      maintain its components, its structure, and its function despite both external
      changes and endogenous fluctuations. Live systems are surprisingly robust, as
      they are able to not only preserve their physicochemical architecture in the face
      of variable nutritional and environmental conditions, but also tolerate
      stochastic variability in the concentrations of their components, fix errors
      resulting from hazardous events, and make virtually perfect copies of themselves.
      These qualities have started to be comprehended in full only since the
      application of network theory formalisms to regulatory phenomena. This review
      addresses the distinct role of network architecture (topology, logic) and
      biochemical/kinetic parameters in the materialization of various archetypical
      robust gene expression circuits in prokaryotes. Some take-home lessons for the
      construction of artificial regulatory networks (one of the trademarks of
      synthetic biology) are to be derived from such state of affairs.

PMID- 20825347
TI  - Bacterial shape: two-dimensional questions and possibilities.
AB  - Events in the past decade have made it both possible and interesting to ask how
      bacteria create cells of defined length, diameter, and morphology. The current
      consensus is that bacterial shape is determined by the coordinated activities of
      cytoskeleton complexes that drive cell elongation and division. Cell length is
      most easily explained by the timing of cell division, principally by regulating
      the activity of the FtsZ protein. However, the question of how cells establish
      and maintain a specific and uniform diameter is, by far, much more difficult to
      answer. Mutations associated with the elongation complex often alter cell width,
      though it is not clear how. Some evidence suggests that diameter is strongly
      influenced by events during cell division. In addition, surprising new
      observations show that the bacterial cell wall is more highly malleable than
      previously believed and that cells can alter and restore their shapes by relying
      only on internal mechanisms.

PMID- 20825350
TI  - Genetic diversity among offspring from archived Salmonella enterica ssp. enterica
      serovar typhimurium (Demerec Collection): in search of survival strategies.
AB  - Extensive phenotypic and genomic diversity was detected among offspring of
      Salmonella enterica ssp. enterica serovar Typhimurium LT2 (nonmutator) and LT7
      (mutator, mutL) strains after decades of storage in sealed nutrient agar stabs.
      In addition to numerous losses in carbon and nitrogen metabolism, the acquired
      new metabolites indicated that alternate pathways were established. Particularly
      striking was the array of phage types when this phenotype was expected to be a
      stable feature. Evidence is presented regarding the role of mutator gene mutL(-)
      in the establishment of diversity as well as the ability of cells to return to
      mutL(+) genetic stabilization. Mutations included deletions, duplications,
      frameshifts, inversions and transpositions. In competition tests, survivors were
      more fit than were wild type. Because survival strategies continue to intrigue
      microbiologists, observations are compared with those of others who have
      addressed related questions. A brief genealogy of the archived strains is also
      recorded.

PMID- 20825351
TI  - Letting sleeping dos lie: does dormancy play a role in tuberculosis?
AB  - Mycobacterium tuberculosis, which causes tuberculosis, remains a major human
      public health threat. This is largely due to a sizeable reservoir of latently
      infected individuals, who may relapse into active disease decades after first
      acquiring the infection. Furthermore, patients have a very slow response to
      treatment of active disease. Latency and antibiotic tolerance are commonly taken
      as a proxy for dormancy, a stable nonreplicative state. However, latency is a
      clinical term that is solely defined by a lack of disease indicators. The actual
      state of the bacterium in human latency is not well understood. Here we evaluate
      the results of several in vitro models of dormancy and consider the applicability
      of various animal models for studying aspects of human latency and resistance to
      killing by antibiotics. Furthermore, we propose a model for the initiation of
      dormancy and resuscitation during infection.

PMID- 20825352
TI  - Mechanosensitive channels in microbes.
AB  - All cells, including microbes, detect and respond to mechanical forces, of which
      osmotic pressure is most ancient and universal. Channel proteins have evolved
      such that they can be directly stretched open when the membrane is under turgor
      pressure. Osmotic downshock, as in rain, opens bacterial mechanosensitive (MS)
      channels to jettison osmolytes, relieving pressure and preventing cell lysis. The
      ion flux through individual channel proteins can be observed directly with a
      patch clamp. MS channels of large and small conductance (MscL and MscS,
      respectively) have been cloned, crystallized, and subjected to biophysical and
      genetic analyses in depth. They are now models to scrutinize how membrane forces
      direct protein conformational changes. Eukaryotic microbes have homologs from
      animal sensory channels of the TRP superfamily. The MS channel in yeast is also
      directly sensitive to membrane stretch. This review examines the key concept that
      proteins embedded in the lipid bilayer can respond to the changes in the
      mechanical environment the lipid bilayer provides.

PMID- 20825353
TI  - Bacterial microcompartments.
AB  - Bacterial microcompartments (BMCs) are organelles composed entirely of protein.
      They promote specific metabolic processes by encapsulating and colocalizing
      enzymes with their substrates and cofactors, by protecting vulnerable enzymes in
      a defined microenvironment, and by sequestering toxic or volatile intermediates.
      Prototypes of the BMCs are the carboxysomes of autotrophic bacteria. However,
      structures of similar polyhedral shape are being discovered in an ever-increasing
      number of heterotrophic bacteria, where they participate in the utilization of
      specialty carbon and energy sources. Comparative genomics reveals that the
      potential for this type of compartmentalization is widespread across bacterial
      phyla and suggests that genetic modules encoding BMCs are frequently laterally
      transferred among bacteria. The diverse functions of these BMCs suggest that they
      contribute to metabolic innovation in bacteria in a broad range of environments.

PMID- 20825354
TI  - Bacterial sensor kinases: diversity in the recognition of environmental signals.
AB  - Bacteria sense and respond to a wide range of physical and chemical signals.
      Central to sensing and responding to these signals are two-component systems,
      which have a sensor histidine kinase (SK) and a response regulator (RR) as basic
      components. Here we review the different molecular mechanisms by which these
      signals are integrated and modulate the phosphorylation state of SKs. Apart from
      the basic mechanism, which consists of signal recognition by the SK that leads to
      an alteration of its autokinase activity and subsequently a change in the RR
      phosphorylation state, a variety of alternative modes have evolved. The
      biochemical data available on SKs, particularly their molecular interactions with
      signals, nucleotides, and their cognate RRs, are also reviewed.

PMID- 20825355
TI  - Use of interferon-alpha in two patients with Merkel cell carcinoma positive for
      Merkel cell polyomavirus.

PMID- 20825356
TI  - Changes in resting energy expenditure (REE) as a function of tumor response to
      sunitinib in a cachexic patient with a metastatic endocrine tumor of the
      pancreas.

PMID- 20825358
TI  - Prevalence and severity of echocardiographic left ventricular hypertrophy in
      hypertensive patients in clinical practice.
AB  - BACKGROUND AND AIM: The prevalence of left ventricular hypertrophy (LVH) in human
      hypertension has been mostly documented in population-based samples and selected
      hypertensive cohorts. Rather scant data are available from clinical practice.
      Thus, we examined the prevalence of LVH in a large group of hypertensive patients
      referred by general practitioners to a routine echocardiographic examination.
      METHODS: A total of 2249 hypertensive subjects (mean age 62 years, 52.3% men,
      84.5% treated) referred by their practitioners to 17 outpatient echocardiographic
      laboratories across Italy for detection of hypertensive early cardiac damage were
      included in the study. LVH was defined as left ventricular mass (A) >= 225/163 g,
      (B) >= 116/96 g/m(2), (C) >= 49/45 g/m(2.7) in men/women, respectively; LVH was
      graded as mild, moderate and severe according to Lang's report. RESULTS: Overall,
      patients with LVH were 58%, 58% and 65% by criteria A, B and C, respectively. LVH
      was mild in 33% (A), 36% (B) and 29% (C), moderate in 31% (A), 28% (B) and 27%
      (C), and severe in 36% (A), 36% (B) and 44% (C). CONCLUSIONS: Data provided by
      this multicentre nationwide survey support the view that, despite therapeutic
      interventions, LVH remains a highly frequent phenotype in human hypertension and
      that severe LVH is present in a large fraction of hypertensives.

PMID- 20825359
TI  - A systematic literature review of quality of life in lower limb amputees.
AB  - PURPOSE: To systematically review studies on quality of life (QoL) in lower limb
      amputees. METHOD: Computerised literature search of MEDLINE, CINAHL, PUBMED and
      PsycINFO databases was performed using the keywords, amputee, leg, knee, foot,
      amputation, QoL, prosthesis, orthopaedic equipment, ADL, phantom, mobility,
      rehabilitation, psychosocial, psychology and social. Eligible studies published
      from database inception through March 2009 were selected. The study was included
      if (1) the study population comprised of adolescent and adult lower-limb amputees
      as a group or a sub-group, and had ten or more subjects; (2) the study involved
      subjective assessment of QoL or self-appraisal of life or satisfaction with life;
      (3) the study was an empirical research study and (4) at least one of the study
      outcomes was QoL or self-appreciation of life, and QoL results were presented.
      The selected articles were assessed for study quality based on a standardised set
      of 19 criteria. The criteria list was pilot-tested for applicability and
      operationalisation by the authors. Objectives, study population description, QoL
      instruments used and study outcomes were summarised for the included studies.
      RESULTS: Twenty-six articles met the inclusion criteria. Fifteen studies were
      cross-sectional, four prospective, six retrospective and one mixed study-design.
      The studies were found to be heterogeneous with respect to the study objectives
      and instruments used to assess QoL. The summary quality score was 50% or more for
      ten studies, with the maximum being 81%. CONCLUSIONS: Lacunas were found in the
      methodological and study population characteristics of most of the studies.
      Prospective longitudinal studies are envisaged to systematically study the events
      following amputation, and the change in QoL over time. To enable this, amputee
      specific standardised and validated QoL instruments are needed to capture the
      multitude of facets influencing QoL in amputees, and thereby, facilitating direct
      comparison across studies.

PMID- 20825360
TI  - Heterotopic autologous chondrocyte transplantation--a realistic approach to
      support articular cartilage repair?
AB  - Injured articular cartilage is limited in its capacity to heal. Autologous
      chondrocyte transplantation (ACT) is a suitable technique for cartilage repair,
      but it requires articular cartilage biopsies for sufficient autologous
      chondrocyte expansion in vitro. Hence, ACT is restricted by donor-site morbidity
      and autologous articular chondrocytes availability. The use of nonarticular
      heterotopic chondrocytes such as auricular, nasoseptal, or costal chondrocytes
      for ACT might overcome these limitations: heterotopic sources show lesser donor
      site morbidity and a comparable extracellular cartilage matrix synthesis profile
      to articular cartilage. However, heterotopic (h)ACT poses a challenge. Particular
      tissue characteristics of heterotopic cartilage, divergent culturing
      peculiarities of heterotopic chondrocytes, and the advantages and drawbacks
      related to these diverse cartilage sources were critically discussed. Finally,
      available in vitro and in vivo experimental (h)ACT approaches were summarized.
      The quality of the cartilage engineered using heterotopic chondrocytes remains
      partly controversy due to the divergent methodologies and culture conditions
      used. While some encouraging in vivo results using (h)ACT have been demonstrated,
      standardized culturing protocols are strongly required. However, whether
      heterotopic chondrocytes implanted into joint cartilage defects maintain their
      particular tissue properties or can be adapted via tissue engineering strategies
      to fulfill regular articular cartilage functions requires further studies.

PMID- 20825361
TI  - Design of nano- and microfiber combined scaffolds by electrospinning of collagen
      onto starch-based fiber meshes: a man-made equivalent of natural extracellular
      matrix.
AB  - Mimicking the structural organization and biologic function of natural
      extracellular matrix has been one of the main goals of tissue engineering.
      Nevertheless, the majority of scaffolding materials for bone regeneration
      highlights biochemical functionality in detriment of mechanical properties. In
      this work we present a rather innovative construct that combines in the same
      structure electrospun type I collagen nanofibers with starch-based microfibers.
      These combined structures were obtained by a two-step methodology and
      structurally consist in a type I collagen nano-network incorporated on a macro
      starch-based support. The morphology of the developed structures was assessed by
      several microscopy techniques and the collagenous nature of the nano-network was
      confirmed by immunohistochemistry. In addition, and especially regarding the
      requirements of large bone defects, we also successfully introduced the concept
      of layer by layer, as a way to produce thicker structures. In an attempt to
      recreate bone microenvironment, the design and biochemical composition of the
      combined structures also envisioned bone-forming cells and endothelial cells
      (ECs). The inclusion of a type I collagen nano-network induced a stretched
      morphology and improved the metabolic activity of osteoblasts. Regarding ECs, the
      presence of type I collagen on the combined structures provided adhesive support
      and obviated the need of precoating with fibronectin. It was also importantly
      observed that ECs on the nano-network organized into circular structures, a three
      dimensional arrangement distinct from that observed for osteoblasts and
      resembling the microcappillary-like organizations formed during angiogenesis. By
      providing simultaneously physical and chemical cues for cells, the herein
      proposed combined structures hold a great potential in bone regeneration as a man
      made equivalent of extracellular matrix.

PMID- 20825362
TI  - The therapeutic potential of the Wnt signaling pathway in bone disorders.
AB  - The Wnt pathway plays a critical role in development and differentiation of many
      tissues, such as the gut, hair follicles, and bone. Increasing evidence indicates
      that Wnts may function as key regulators in osteogenic differentiation of
      mesenchymal stem cells and bone formation. Conversely, aberrant Wnt signaling is
      associated with many osteogenic pathologies. For example, genetic alterations in
      the Wnt signaling pathway lead to osteoporosis and osteopenia, while inactivating
      mutations of Wnt inhibitors result in a hyperostotic skeleton with increased bone
      mineral density. Hyperparathyroidism causes osteopenia via induction of the Wnt
      signaling pathway. Lithium, often used to treat bipolar disorder, blocks a Wnt
      antagonist, decreasing the patient's risk of fractures. Thus, manipulating the
      Wnt pathway may offer plenty therapeutic opportunities in treating bone
      disorders. In fact, induction of the Wnt signaling pathway or inhibition of Wnt
      antagonists has shown promise in treating bone metabolic disorders, including
      osteoporosis. For example, antibodies targeting the Wnt inhibitor Sclerostin lead
      to increased bone mineral density in post-menopausal women. However, such
      therapies targeting the Wnt pathway are not without risk, as genetic alternations
      may lead to over-activation of Wnt/beta-catenin and its association with many
      tumors. It is conceivable that targeting Wnt inhibitors may predispose the
      individuals to tumorigenic phenotypes, at least in bone. Here, we review the
      roles of Wnt signaling in bone metabolic and pathologic processes, as well as the
      therapeutic potential for targeting Wnt pathway and its associated risks in bone
      diseases.

PMID- 20825363
TI  - Neurosteroids and hepatic encephalopathy: an update on possible pathophysiologic
      mechanisms.
AB  - Cerebral complications of liver failure either due to chronic or acute
      manifestations lead to a neurological disorder known as Hepatic encephalopathy
      (HE). Neurosteroids, synthesized in the brain mainly by astrocytes but also in
      other brain cells independently from peripheral steroidal sources such as adrenal
      and gonads, are suggested to play a role in the pathogenesis of HE. The
      mechanisms by which neurosteroids affects brain function are not totally
      elucidated but may involve both genomic and non genomic effects. On one hand,
      neurosteroids bind and modulate different types of neuronal membrane receptors.
      While neurosteroid may affect directly postsynaptic receptors including GABA(A),
      5-HT3, NMDA, glycine, and opioid receptors which have been involved in HE,
      neurosteroids effects through GABA(A) receptors may also compromise indirectly
      the function of neurons networking with GABAergic interneurons. On the other
      hand, some neurosteroids bind to intracellular receptors through which they also
      regulate gene expression, and there is substantial evidence confirming that
      expression of genes coding for key astrocytic and neuronal proteins are altered
      in HE. The mechanisms that trigger brain neurosteroid changes in HE are not yet
      well-known, but could involve (i) ammonia and manganese (in chronic HE)-induced
      translocator protein (TSPO) activation, (ii) neuroinflammation or (iii) blood
      brain transfer of lipophylic neuroactive steroids. The present review summarizes
      evidence for the involvement of neurosteroids in HE and possible mechanisms for
      their altered brain production and central effects in human and experimental HE.

PMID- 20825364
TI  - Sobering thoughts at seventy on trivia and serendipity.
AB  - The Editor-in-Chief reflects on a life in biological sciences that has been
      rewarding through the sheer diversity of interesting phenomenon he has
      researched, and recalls how holistic thinking had sadly been replaced by rampant
      reductionism.

PMID- 20825365
TI  - Neuroadipology: a novel component of neuroendocrinology.
AB  - Adipose tissue is a dynamic endocrine and paracrine organ producing a large
      number of signalling proteins collectively termed adipokines. Some of them are
      mediators in the cross-talk between adipose tissue and the brain in regulating
      food intake and energy homoeostasis. However, the hypothalamus is not the only
      brain target for adipokines, and food intake is not the only biological effect of
      these signals. Rather, some adipokines support various cognitive functions and
      exert neurotrophic activity. Current data on adipose-derived neuropeptides,
      neurotrophic factors, pituitary hormones and hypothalamic releasing factors is
      highlighted in this review. We propose that adipose tissue is a member of the
      diffuse neuroendocrine system. Cumulatively, this is conceptualized as
      neuroadipology, a new example of a link between neurobiology and other topics,
      such as neuroimmunology and neuroendocrinology. Because adipose tissue is a bona
      fide endocrine organ, neuroadipology may be considered a new discipline in
      neuroendocrinology. It may have a wide-ranging potential within a variety of
      neuronal and metabolic functions in health and disease.

PMID- 20825366
TI  - Prevention of diabetic nephropathy in Ins2(+/)-(AkitaJ) mice by the mitochondria
      targeted therapy MitoQ.
AB  - Mitochondrial production of ROS (reactive oxygen species) is thought to be
      associated with the cellular damage resulting from chronic exposure to high
      glucose in long-term diabetic patients. We hypothesized that a mitochondria
      targeted antioxidant would prevent kidney damage in the Ins2(+/)-(AkitaJ) mouse
      model (Akita mice) of Type 1 diabetes. To test this we orally administered a
      mitochondria-targeted ubiquinone (MitoQ) over a 12-week period and assessed
      tubular and glomerular function. Fibrosis and pro-fibrotic signalling pathways
      were determined by immunohistochemical analysis, and mitochondria were isolated
      from the kidney for functional assessment. MitoQ treatment improved tubular and
      glomerular function in the Ins2(+/)-(AkitaJ) mice. MitoQ did not have a
      significant effect on plasma creatinine levels, but decreased urinary albumin
      levels to the same level as non-diabetic controls. Consistent with previous
      studies, renal mitochondrial function showed no significant change between any of
      the diabetic or wild-type groups. Importantly, interstitial fibrosis and
      glomerular damage were significantly reduced in the treated animals. The pro
      fibrotic transcription factors phospho-Smad2/3 and beta-catenin showed a nuclear
      accumulation in the Ins2(+/)-(AkitaJ) mice, which was prevented by MitoQ
      treatment. These results support the hypothesis that mitochondrially targeted
      therapies may be beneficial in the treatment of diabetic nephropathy. They also
      highlight a relatively unexplored aspect of mitochondrial ROS signalling in the
      control of fibrosis.

PMID- 20825367
TI  - Immunomodulation by a combination of nitric oxide and glucocorticoids in a human
      endotoxin model.
AB  - BACKGROUND: inflammatory reactions arise in reaction to a variety of pathogenic
      insults. The combination of inhaled nitric oxide (iNO) and glucocorticoids (GC)
      may attenuate endotoxin-induced inflammatory responses. It has been shown that
      the combination of iNO (30 p.p.m.) and steroids blunted the inflammatory response
      in a porcine endotoxin model, but not in humans. Therefore, we investigated
      whether a clinically 'maximal' dose of iNO in combination with GC could modulate
      the systemic inflammatory response in a human endotoxin model. METHODS: a double
      blind, cross-over, placebo-controlled randomized study including 15 healthy
      Caucasian volunteers (five females, 10 males). Performed at the Intensive Care
      Unit in a university hospital. iNO 80 p.p.m. or placebo (nitrogen) was started 2h
      before administration of endotoxin (2 ng/kg). Thirty minutes later, GC (2mg/kg,
      hydrocortisone) was administered intravenously. Blood samples and clinical signs
      were collected before and up to 24 h after the endotoxin injection. RESULTS: body
      temperature and heart rate increased significantly subsequent to endotoxin
      challenge. The plasma levels of IFN-gamma, IL-1beta, IL-2, 4 5, 6, 8, 10, 12, 13
      and TNFalpha were markedly elevated. However, HMGB-1 and sRAGE were unaffected.
      No difference between placebo/GC and iNO/GC treatment was observed in the
      clinical or cytokine response, neither was there any difference between the first
      and the second exposure to endotoxin. CONCLUSIONS: pre-treatment with iNO 80
      p.p.m. along with GC (2mg/kg) administrated after the endotoxin challenge could
      not modulate the systemic inflammatory response in this model of human
      experimental inflammation.

PMID- 20825368
TI  - Circadian aspects of post-operative morbidity and mortality.
AB  - It has been well established that there exists a circadian concentration of
      cardiovascular, cerebrovascular and cardiopulmonary events. The aim was to
      describe aspects of circadian variation in relation to cardiovascular,
      cerebrovascular and thromboembolic diseases and to describe the literature
      concerning post-operative circadian disturbances. We also present the literature
      concerning circadian variation in post-operative morbidity and mortality. PubMed
      and the Cochrane database were searched for papers using a combination of
      'circadian,''surgery,''post-operative,''mortality' and 'morbidity.' Eleven
      relevant studies were found, and seven of these were excluded due to the use of
      time of surgery and not time of morbidity or mortality as the main variable. The
      results from the four articles showed a circadian distribution of morbidity and
      mortality that mimics the one seen without surgery. There is a peak incidence of
      myocardial ischemia, fatal thromboembolism and sudden unexpected death in the
      morning hours. A circadian variation exists in post-operative morbidity and
      mortality. The observed circadian variation in post-operative morbidity and
      mortality may warrant a chronopharmacological approach to patients in the
      perioperative period. The underlying pathophysiological mechanisms should be the
      focus for future studies.

PMID- 20825369
TI  - Patient satisfaction with care in the intensive care unit: can we rely on
      proxies?
AB  - BACKGROUND: To investigate whether next of kin can be addressed as proxy to
      assess patients' satisfaction with care in the intensive care unit (ICU).
      METHODS: Prospective observational multicentre study. Two hundred and thirty-five
      patients with an ICU length of stay of >=2 days and 266 of their adult next of
      kin participated. Patient satisfaction was assessed by a questionnaire,
      distributed upon discharge from an ICU and compared with next of kin's answers.
      The possible range of answers was 0-100, with higher numbers indicating higher
      satisfaction. The main outcome measure was the extent of agreement between
      patients' satisfaction with care and the ratings of their next of kin. RESULTS:
      Patients were most satisfied concerning physicians' competence (86.7+/-16.3),
      while least satisfaction was observed for the management of agitation and
      restlessness (78.2+/-23.5). There was no significant difference between next of
      kin's and patients' ratings. Agreement between patients and proxies was the
      highest concerning overall satisfaction (Cohen's kappa 0.40) and the lowest for
      coordination of care (0.24). Spouses/partners had a higher agreement with the
      patients' ratings than other proxies. CONCLUSIONS: If the patient is unable to
      rate his satisfaction with care in the ICU, next of kin may be taken as an
      appropriate surrogate. TRIAL REGISTRATION: The study has been registered at
      ClinicalTrials.gov, Reg No: NTC 00890513.

PMID- 20825370
TI  - The NADH-ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5) gene variants
      are associated with autism.
AB  - OBJECTIVE: Autism appears to have a strong genetic component. The product of the
      NADH-ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5) gene is included in
      the mitochondrial electron transport chain. METHOD: We performed a case-control
      study of 235 patients with autism and 214 controls and examined three single
      nucleotide polymorphisms (SNPs) within this gene in a Japanese population. We
      then conducted a transmission disequilibrium test (TDT) analysis in 148 autistic
      trios. RESULTS: In the case-control study, two SNPs (rs12666974 and rs3779262)
      showed a significant association with autism (P=0.00064 and 0.00046
      respectively). Furthermore, a haplotype containing these two SNPs showed a
      significant association (P-global=0.0013, individual haplotype A-A: P=0.010). In
      TDT analysis, the global and A-A haplotype P-values also indicated significant
      associations. Minor allele and genotype frequencies were decreased in the
      autistic subjects. CONCLUSION: We found significant association between the NDFA5
      gene and autism.

PMID- 20825371
TI  - Mechanisms of cerebrovascular protection: oestrogen, inflammation and
      mitochondria.
AB  - Investigation of oestrogen action reveals a multitude of diverse effects. This
      brief review focuses on the impact of oestrogen on the vasculature, with
      particular emphasis on the cerebral circulation. Three major actions of oestrogen
      are discussed: enhancement of vasodilator capacity, suppression of vascular
      inflammation and increase in mitochondrial efficiency. In both humans and
      animals, oestrogen increases vasodilator tone, an effect dependent on a
      functional endothelium. Two distinct mechanisms are involved: increase in
      endothelial nitric oxide synthase (eNOS) mRNA and protein and phosphorylation of
      eNOS via the PI-3 kinase/Akt pathway. Both effects are mediated by oestrogen
      receptors (ER), but through two pathways, ER-mediated nuclear gene transcription
      and cell membrane-associated ERs respectively. Oestrogen also increases function
      of other endothelium-dependent vasodilators. Oestrogen suppresses vascular
      inflammation through an NF-kappaB-dependent effect. The inflammatory response has
      also been shown to vary significantly during the oestrous cycle of rodents.
      Emerging information shows that oestrogen increases mitochondrial biogenesis and
      decreases superoxide production. Suppression of mitochondrial superoxide
      production by 17beta-estradiol in cerebral blood vessels is mediated by the ER
      alpha receptor and not dependent on increased Mn superoxide dismutase activity.
      Oestrogen treatment also increases protein levels for a number of components of
      the electron transfer chain, as well as levels of transcription factors that
      regulate mitochondrial function. All of these actions of oestrogen could be
      important in mediating vascular protection, especially in the cerebral
      circulation. Furthermore, given the potential of mitochondrial DNA damage to
      contribute to pathophysiology and ageing, mitochondrial protective effects of
      oestrogen might contribute to the longer average lifespan of women.

PMID- 20825372
TI  - Elevated overdose mortality rates among First Nations individuals in a Canadian
      setting: a population-based analysis.
AB  - AIMS: To determine the total burden of illicit drug overdose mortality over the
      study period in the province of British Columbia and investigate possible
      population-level determinants by estimating rates among subgroups including First
      Nations individuals. DESIGN: Review of coroner case files. SETTING: The province
      of British Columbia, Canada. PARTICIPANTS: Individuals dying from an illicit drug
      overdose between 2001 and 2005. MEASUREMENTS: Age-adjusted mortality rates,
      standardized mortality ratios (SMR) and years of potential life lost (YPLL),
      stratified by major population groups. FINDINGS: Over the study period, 909
      individuals died from illicit drug overdoses, including 104 (11.4%) First Nations
      individuals. Compared to the general population, First Nations males and females
      suffered from substantially elevated SMR and YPLL. In a multivariate logistic
      regression analysis, First Nations deaths were significantly more likely to be
      among women, related to injection drug use and to have occurred in the Downtown
      Eastside area of Vancouver, the local epicentre of human immunodeficiency virus
      infection and open drug use (all P< 0.05). CONCLUSIONS: This report found highly
      elevated overdose death rates and levels of premature mortality among First
      Nations Canadians in British Columbia compared to the general population. While
      previously unidentified, these findings are consistent with the poorer population
      health profile of First Nations Canadians. Although further research is needed to
      identify the causes of the elevated death rates, our findings support increased
      availability of evidence-based overdose prevention measures.

PMID- 20825373
TI  - Depressive and manic symptoms are not opposite poles in bipolar disorder.
AB  - OBJECTIVE: This study of 236 individuals with bipolar disorders employed
      longitudinal analyses to determine whether the symptoms of mania and depression
      can be understood as one dimension (with depression and mania as opposites) or
      two relatively independent dimensions. METHOD: Weekly severity ratings of manic
      and depression were assessed using the Longitudinal Interval Follow-up Evaluation
      II for 72 weeks. The within-subjects correlation of manic and depressive severity
      was examined using random effects regression. RESULTS: Contrary to the one
      dimension model, mania and depression symptoms were not negatively related.
      Indeed, the correlations of mania with depressive symptoms were quite small.
      CONCLUSION: The data suggest that depressive and manic symptoms are not opposite
      poles. Rather depressive and manic symptoms appear to fluctuate relatively
      independently within bipolar disorder.

PMID- 20825374
TI  - The peritoneal leptin, MCP-1 and TNF-alpha in the pathogenesis of endometriosis
      associated infertility.
AB  - PROBLEM: To explore the roles of leptin, monocyte chemotactic protein (MCP)-1,
      and tumour necrosis factor (TNF)-alpha in the peritoneal fluid (PF) in the
      pathogenesis of endometriosis-associated infertility. METHOD OF STUDY: Leptin,
      MCP-1, and TNF-alpha levels in the PF from 28 infertile women with endometriosis
      (study group), 23 women with fallopian-associated infertility (controls), and 24
      women with myoma (controls) were determined by performing enzyme-linked
      immunosorbent assay (ELISA). RESULT: Leptin and TNF-alpha levels in the PF showed
      no significant difference among three groups. The MCP-1 level in patients with
      endometriosis was higher than those in fallopian-associated infertility group and
      myoma group (P < 0.01). There was a positive correlation between leptin and MCP-1
      levels in the PF of patients with endometriosis (P < 0.05). CONCLUSION:
      Peritoneal leptin and MCP-1 play important roles in the pathogenesis of
      infertility in the early stage of endometriosis.

PMID- 20825376
TI  - Recurrent pregnancy loss and apolipoprotein E gene polymorphisms.

PMID- 20825375
TI  - Cytokine dysregulation in early- and late-term placentas from feline
      immunodeficiency virus (FIV)-infected cats.
AB  - PROBLEM: Experimental infection of cats with FIV-B-2542 produces high rates of
      fetal infection and reproductive failure. We hypothesized that dysregulation of
      placental cytokine expression occurs in FIV-infected queens, and aberrant
      expression potentiates inflammation and impacts pregnancy outcome. Our purpose
      was to quantify expression of representative pro-inflammatory cytokines (IL-6, IL
      12p35, and IL-1beta), IL-10 (anti-inflammatory), and the chemokine SDF-1alpha in
      early- and late-term placental tissues. METHOD OF STUDY:  Real-time reverse
      transcriptase PCR was used to measure gene expression in placental tissues.
      RESULTS:  Increased expression of IL-6 and IL-12p35 and decreased expression of
      IL-10 occurred in FIV-infected tissues at early pregnancy; at late gestation, IL
      6 expression increased and IL-1beta and SDF-1alpha decreased. At late pregnancy,
      IL-6 expression positively correlated with FIV load. IL-12:IL-10 ratios were
      higher in infected tissues at early, but not late pregnancy. Fetal non-viability
      accompanied decreased IL-12p35 and SDF-1alpha expression at both stages and
      decreased IL-12:IL-10 ratio at late pregnancy. CONCLUSION: FIV infection caused a
      pro-inflammatory placental microenvironment at early, but not late pregnancy.

PMID- 20825377
TI  - Bone morphogenetic protein-2 (BMP-2) increases gene expression of FSH receptor
      and aromatase and decreases gene expression of LH receptor and StAR in human
      granulosa cells.
AB  - PROBLEM: A growing body of evidence indicates that bone morphogenetic protein
      (BMP) cytokines play a key role in female fertility in mammals. BMP-2 is known to
      be expressed in the ovary of many species. In the present study, we examined the
      expression and function of BMP-2 in the human ovary. METHOD OF STUDY: BMP-2 mRNA
      expression in the human ovary was evaluated by in situ hybridization. Human
      granulosa cells were obtained from in vitro fertilization patients. Human
      granulosa cells were cultured with recombinant BMP-2 or human chorionic
      gonadotrophin (HCG), followed by RNA extraction. RESULTS: BMP-2 expression was
      detected in granulosa cells of antral follicles but not of corpus luteum. The in
      vitro study showed that BMP-2 induced follicular stimulating hormone (FSH)
      receptor and aromatase expression, while decreasing luteinizing hormone (LH)
      receptor and steroidogenic acute regulatory protein expression in human granulosa
      cells. HCG decreased gene expression of BMP-2 and increased BMP and activin
      membrane-bound inhibitor (BAMBI), an antagonist of BMP-2. CONCLUSION: Expression
      and disappearance of BMP-2 might contribute to folliculogenesis and luteinization
      by regulating gonadotropin receptor expression in human granulosa cells. HCG can
      modulate BMP-2 function by controlling BMP-2 and BAMBI expression.

PMID- 20825378
TI  - The distribution of CD56(dim) CD16+ and CD56(bright) CD16- cells are associated
      with prolactin levels during pregnancy and menstrual cycle in healthy women.
AB  - PROBLEM: The pregnancy and menstrual cycle (MC) are the main physiologic events
      linked to the human reproduction. An adequate neuroendocrine axis is mandatory
      for the homeostasis in both events. To analyze the distribution of NK, T, Treg
      cells, expression of their receptors and to associate with hormone levels in
      pregnant and MC in healthy women. METHOD OF STUDY: We studied two groups of
      healthy women: 13 pregnant women followed up at 1st, 2nd and 3rd trimesters and
      11 women in the 5th and 21st day of the MC. The distribution of NK, T, Treg cells
      population, expression of their receptors and hormone levels were quantified.
      RESULTS: In pregnant women, we found an association of NK cells CD56(dim) CD16(+)
      with prolactin levels. This finding was also was observed for CD56(brigthCD16-)
      being statistical significant during 1st trimester for both subpopulations.
      During MC, correlation of CD56(dim) CD16(+) , CD56(bright) CD16(-) cells with
      prolactin in follicular and luteal phase was found. CONCLUSION: This is the first
      report where these cell subpopulations have been analyzed prospectively. Even we
      can argue the random effect for the small number of women is interesting that
      prolactin showed the more consistent correlation with CD56(dim) CD16(+) ,
      CD56(brigth) CD16(-) cells during both events studied.

PMID- 20825379
TI  - Proportion of invariant NKT cells in normal pregnant women at term: an evaluation
      in peripheral blood, placenta and umbilical cord blood.

PMID- 20825381
TI  - Immunologic characteristics of preeclampsia, a comprehensive review.
AB  - Preeclampsia (PE) remains a leading cause of maternal and fetal morbidity and
      mortality. Despite decades of intense research on the problem, there is no early
      pregnancy screening test to recognize those at risk. Recently, altered immune
      responses have been suspected to be involved in preeclampsia pathogenesis, which
      may involve the inflammatory context in which an immune response is mounted. In
      this review, the immunologic pathogenesis of the PE is reviewed in context of
      innate and adaptive immunity (both cellular, i.e., T and NK cells, and humoral
      immunity) in relation to thrombophilic conditions.

PMID- 20825380
TI  - Regulation of inflammation by the NF-kappaB pathway in ovarian cancer stem cells.
AB  - PROBLEM: The NFkappaB pathway is a major source of pro-inflammatory cytokines,
      which may contribute to cancer chemoresistance. We showed that constitutive
      NFkappaB activity is characteristic of the ovarian cancer stem cells (OCSCs). The
      aim of this study is to determine whether the inhibition of NFkappaB by
      Eriocalyxin B (EriB) in the OCSCs may induce cell death in otherwise
      chemoresistant cells. METHODS: OCSCs and mature ovarian cancer cells (mOCCs) were
      treated with increasing concentrations of EriB. Cell viability was measured using
      the Celltiter 96 assay, and caspase activity was quantified using Caspase-GloTM
      assay. Cytokine levels were quantified using xMAP technology. RESULTS: EriB
      decreased the percent of viable cells in all cultures tested with GI(50) of 0.5-1
      MUm after 48 hrs of treatment. The intracellular changes associated with EriB
      induced cell death are: (i) inhibition of NF-kappaB activity; (ii) decreased
      cytokine production; (iii) activation of caspases; and (iv) down-regulation of
      XIAP. In addition, EriB is able to sensitize OCSCs to TNFalpha and FasL-mediated
      cell death. CONCLUSION: Inhibition of the NFkappaB pathway induces cell death in
      the OCSCs. Because the OCSCs may represent the source of recurrence and
      chemoresistance, the use of NFkappaB inhibitors like EriB may prevent recurrence
      in patients with ovarian cancer.

PMID- 20825382
TI  - US Health Care Reform and Transplantation, Part II: impact on the public sector
      and novel health care delivery systems.
AB  - The Patient Protection and Affordable Care Act passed in 2010 will result in
      dramatic expansion of publically funded health insurance coverage for low-income
      individuals. It is estimated that of the 32 million newly insured, 16 million
      will obtain coverage through expansion of the Medicaid Program, and the remaining
      16 million will purchase coverage through their employer or newly legislated
      insurance exchanges. While the Act contains numerous provisions to improve access
      to private insurance as discussed in Part I of this analysis, public sector
      coverage will significantly be affected. The cost of health care reform will be
      borne disproportionately by Medicare, which faces nearly $500 billion in cuts to
      be identified by a new independent board. Transplant centers should be concerned
      about the impact of the reform on the financial aspects of transplantation. In
      addition, this legislation also utilizes the Medicare Program to drive reform of
      the health care delivery system, by encouraging the development of integrated
      Accountable Care Organizations, experimentation with new 'models' of healthcare
      delivery, and expanded support for Comparative Effectiveness Research. Transplant
      providers, including transplant centers and physicians/surgeons need to lead this
      movement, drawing on our experience providing comprehensive multidisciplinary
      care under global budgets with publically reported outcomes.

PMID- 20825383
TI  - US Health Care Reform and Transplantation. Part I: overview and impact on access
      and reimbursement in the private sector.
AB  - The Health Care Reform (HCR) legislation passed by Congress in 2010 will have
      significant impact on transplant centers, patients and health care professionals.
      The Act seeks to expand coverage, limit the growth in health care costs and
      reform the delivery and insurance systems. In Part I of this two part series, we
      provide an overview and perspective of changes in private health insurance
      resulting from HCR. Under the plan, all Americans will be required to purchase
      coverage through their employer or via an improved individual/small group market.
      This legislation limits abusive practices such as limitations on preexisting
      conditions, lifetime and annual coverage limitations and dropping of
      beneficiaries if they become sick. The legislation will also limit high-cost
      plans and regulate premium increases. Private sector reforms are likely to
      benefit our patients by increasing the number of patients with access to
      transplant services, since the use of 'preexisting' conditions will be
      eliminated. However without a concomitant increase in the organ supply, longer
      waiting times and greater use of marginal organs are likely to increase the cost
      of transplant. Furthermore, transplant providers will receive reduced
      reimbursement as a result of market consolidation and the growing power of large
      transplant networks.

PMID- 20825385
TI  - Which patients with ESRD are willing to pay for a kidney?

PMID- 20825384
TI  - Skeletal integrity and visceral transplantation.
AB  - Despite continuous improvement in long-term survival, there is no knowledge about
      risk of bone health impairment and management strategies before and after
      intestinal transplantation. Therefore, 147 adults were retrospectively studied
      via chart review; 70 long-term survivors, 53 candidates and 24 recipients with
      longitudinal follow-up. Evaluation process included measurement of bone mineral
      density (BMD) and allied biochemical markers. Both long-term survivors and
      candidates showed low bone mass with lower (p < 0.05) z-scores at hip, femoral
      neck and spine. Vitamin D deficiency and secondary hyperparathyroidism were
      observed in both groups. Prevalence of osteoporosis was 44% among long-term
      survivors and 36% in candidates with age, BMD, duration of parenteral nutrition,
      type of immunosuppression and rejection being significant risk factors. Fragility
      fractures occurred at a higher (p = 0.02) rate among long-term survivors (20%)
      compared to candidates (6%). The longitudinal study documented acceleration (p =
      0.025) of bone loss after transplantation with a decline of 13.4% (femoral neck),
      12.7% (hip) and 2.1% (spine). Alendronate reduced (p < 0.05) but did not prevent
      bone loss. In conclusion, intestinal transplant recipients are at risk of
      osteoporosis secondary to bone loss before and after transplantation.
      Accordingly, current management includes comprehensive preventive measures with
      prompt therapeutic intervention utilizing intravenous bisphosphonates or
      subcutaneous human PTH.

PMID- 20825386
TI  - Morphological characteristics of the canine and feline stomach mucosa.
AB  - The stomach mucosa structure in animals belonging to Order Carnivora indicates
      some specific characteristics in comparison with the other mammals. Between the
      bases of the mucosal glands and the lamina muscularis mucosae there is an
      additional plate which most of the morphologists have defined as lamina
      subglandularis. In currently used Nomina histologica this layer is indicated as
      stratum compactum in carnivorous stomach mucosa. The investigation aims were to
      study and compare canine and feline stomach tunica mucosa characteristics as well
      as to measure the thickness of stratum compactum and to specify some of the
      certain collagen types and fibronectin compounds. Conventional and differential
      histological and ultrastructural methods and immuno-histochemical approaches for
      investigation of the canine and feline stomach samples were used. The specific
      organization of the carnivorous stomach wall arrangement was established. In the
      structure of the canine stomach mucosa, no evidence of stratum compactum was
      observed. The presence of stratum compactum in feline stomach mucosa was
      ascertained and measured. Using an immunohistochemical method very high
      expression of collagen type IV and fibronectin, moderate positive reaction of
      collagen type III, and a comparatively weakest expression of collagen types I and
      V in the structure of stratum compactum from cat stomach mucosa was shown. The
      obtained results clarify the characteristics of the stomach mucosa morphology and
      could be used as a basis for distinguishing the stomach wall structure of the
      animal species belonging to Canidae and Felidae families although they are both
      carnivores.

PMID- 20825387
TI  - Role of the mesonephros as a transient haematopoietic organ in the bovine embryo.
AB  - During vertebrate embryogenesis, haematopoietic stem cells (HSC) arise in the
      aorta-gonads-mesonephros (AGM) region. In the present study, we examined serial
      sections of 22-34 days post-insemination (dpi) bovine embryos, a species with a
      well-developed and functional mesonephros. We describe the temporo-spatial
      distribution of presumptive c-kit positive HSC and the occurrence of
      haematopoietic foci in the mesonephros and fetal liver using specific antibodies
      directed against haematopoietic cell markers and conventional electron
      microscopy. In the mesonephros, presumptive HSC were found at 23-24 dpi in the
      blood stream, in the endothelial lining of the filtering capillaries and in the
      septal stroma of the cranial part of the mesonephros, the mesonephric giant
      corpuscle (MGC), suggesting a colonalization via the blood stream from the
      haematopoietic clusters of the dorsal aorta. From 25 to 30 dpi, presumptive HSC
      predominate in the septal stroma of the MGC, were they first expand but then
      decline and disappear following 32 dpi. In parallel, we found ongoing
      erythropoiesis and myelopoiesis starting in the MGC at 24 dpi and extending
      during the complete observation period. In the embryonic liver, colonization with
      presumptive c-kit positive HSC occurs slightly later, at 25 dpi. Active formation
      of blood cells in the liver increases following 30 dpi. In conclusion, the
      mesonephros of bovine embryos, in particular its MGC, functions as a primitive
      haematopoietic organ, temporarily intercalated between extraembryonic
      erythropoiesis and haematopoiesis within in the fetal liver, thus recapitulating
      for a short period a phylogenetically old site of blood formation.

PMID- 20825388
TI  - Acute 1,2,3-trichloropane poisoning: a case report and literature review.
AB  - 1,2,3-Trichloropropane is widely used in industrial and agricultural production.
      However 1,2,3-trichloropropane poisoning has been rarely encountered in clinical
      practices. Here, a 45-year-old farmer who suffered fulminant hepatic failure due
      to ingestion of 1,2,3-trichloropropane has been reported and literature about
      1,2,3-trichloropane poisoning has been reviewed. For this case, reduced
      glutathione, vitamin K, pantoprazole were infused intravenously, and transfusion
      of blood plasma, platelets and red blood cells were carried out. Unfortunately,
      the patient's family gave up treatment and they left the hospital with the
      patient because of the low chance of recovery 20 hr after admission. Based on
      blood toxicology screening, patient history and rapid deterioration of the
      patient, the cause of fulminant hepatic failure was determined to be acute
      intoxication of 1,2,3-trichloropropane by unintentional toxicity. 1,2,3
      trichloropropane has histopathological toxic effects on many organs and this
      toxic effect occurs within a short period after ingestion, with liver as the
      major affected organ.

PMID- 20825389
TI  - Stereo-selective metabolism of methadone by human liver microsomes and cDNA
      expressed cytochrome P450s: a reconciliation.
AB  - In vitro metabolism of methadone was investigated in cytochrome P450 (CYP)
      supersomes and phenotyped human liver microsomes (HLMs) to reconcile past
      findings on CYP involvement in stereo-selective metabolism of methadone. Racaemic
      methadone was used for incubations; (R)- and (S)-methadone turnover and (R)- and
      (S)-EDDP formation were determined using chiral liquid chromatography-tandem mass
      spectrometry. CYP supersome activity for methadone use and EDDP formation ranked
      CYP2B6 > 3A4 > 2C19 > 2D6 > 2C18, 3A7 > 2C8, 2C9, 3A5. After abundance scaling,
      CYP3A4, 2B6 and 2C19 accounted for 63-74, 12-32 and 1. 4-14% of respective
      activity. CYP2B6, 2D6 and 2C18 demonstrated a preference for (S)-EDDP formation;
      CYP2C19, 3A7 and 2C8 for (R)-EDDP; 3A4 none. Correlation analysis with 15 HLMs
      supported the involvement of CYP2B6 and 3A. The significant correlation of S/R
      ratio with CYP2B6 activity confirmed its stereo-selectivity. CYP2C19 and 2D6
      inhibitors and monoclonal antibody (mAb) did not inhibit EDDP formation in HLM.
      Chemical and mAb inhibition of CYP3A in high 3A activity HLM reduced EDDP
      formation by 60-85%; inhibition of CYP2B6 in 2B6 high-activity HLM reduced (S)
      EDDP formation by 80% and (R)-EDDP formation by 55%. Inhibition changed methadone
      metabolism in a stereo-selective manner. When CYP3A was inhibited, 2B6 mediated
      (S)-EDDP formation predominated; S/R stereo-selectivity increased. When 2B6 was
      inhibited (S)-EDDP formation fell and stereo-selectivity decreased. The results
      confirmed the primary roles of CYPs 3A4 and 2B6 in methadone metabolism; CYP2C8
      and 2C9 did not appear involved; 2C19 and 2D6 have minimal roles. CYP2B6 is the
      primary determinant of stereo-selective metabolism; stereo-selective inhibition
      might play a role in varied plasma concentrations of the two enantiomers.

PMID- 20825390
TI  - Effects of diverse psychopharmacological substances on the activity of brain
      prolyl oligopeptidase.
AB  - Prolyl oligopeptidase (POP) has been connected to learning, memory and mood.
      Changes in serum or plasma POP activity have been linked to psychiatric
      disorders. POP has been thought to interfere in these conditions by cleaving
      neuroactive peptides or via the phosphatidylinositol second messenger system.
      However, little is known about the possible POP inhibition of commonly used
      psychoactive drugs. In this study, we measured the effects of various
      psychotropic drugs, including antidepressants, antipsychotics, mood stabilisers
      and anxiolytics, on the activity of the rat brain homogenate POP. Of the 38
      compounds tested, 18 inhibited POP by at least 20% at 10 MUM (buspirone,
      chlorpromazine, citalopram, clozapine, desipramine, duloxetine, escitalopram,
      flupenthixol, imipramine, ketanserin, lamotrigine, levomepromazine, prazosin,
      prochlorperazine, promazine, risperidone ritanserin and thioridazine).
      Thioridazine and valproate (VPA) acted at therapeutic plasma levels. Kinetically,
      VPA was a competitive inhibitor, thioridazine a non-competitive inhibitor and
      ketanserin a mixed type inhibitor. Being lipophilic, many of the psychoactive
      compounds are present in the brain at several-times higher concentrations than in
      plasma. At concentrations reported to be reached in the brain, chlorpromazine,
      clozapine, desipramine, imipramine, prochlorperazine and promazine inhibited POP
      by 30-50% suggesting that they could inhibit POP in vivo. However, when studied
      ex vivo, a single dose of 10 mg/kg thioridazine caused a deep sedation in the
      mice but did not inhibit the activity of POP. In conclusion, compared with
      conventional POP inhibitors, all psychopharmacological compounds tested are very
      weak inhibitors in vitro, and we doubt that their POP inhibition would be
      therapeutically meaningful.

PMID- 20825391
TI  - Robust estimation of area under ROC curve using auxiliary variables in the
      presence of missing biomarker values.
AB  - In medical research, the receiver operating characteristic (ROC) curves can be
      used to evaluate the performance of biomarkers for diagnosing diseases or
      predicting the risk of developing a disease in the future. The area under the ROC
      curve (ROC AUC), as a summary measure of ROC curves, is widely utilized,
      especially when comparing multiple ROC curves. In observational studies, the
      estimation of the AUC is often complicated by the presence of missing biomarker
      values, which means that the existing estimators of the AUC are potentially
      biased. In this article, we develop robust statistical methods for estimating the
      ROC AUC and the proposed methods use information from auxiliary variables that
      are potentially predictive of the missingness of the biomarkers or the missing
      biomarker values. We are particularly interested in auxiliary variables that are
      predictive of the missing biomarker values. In the case of missing at random
      (MAR), that is, missingness of biomarker values only depends on the observed
      data, our estimators have the attractive feature of being consistent if one
      correctly specifies, conditional on auxiliary variables and disease status,
      either the model for the probabilities of being missing or the model for the
      biomarker values. In the case of missing not at random (MNAR), that is,
      missingness may depend on the unobserved biomarker values, we propose a
      sensitivity analysis to assess the impact of MNAR on the estimation of the ROC
      AUC. The asymptotic properties of the proposed estimators are studied and their
      finite-sample behaviors are evaluated in simulation studies. The methods are
      further illustrated using data from a study of maternal depression during
      pregnancy.

PMID- 20825392
TI  - The highest confidence density region and its usage for joint inferences about
      constrained parameters.
AB  - Suppose that we are interested in making joint inferences about a set of
      constrained parameters. Confidence regions for these parameters are often
      constructed via a normal approximation of the distribution of a consistent
      estimator for a transformation of the parameters. In this article, we utilize the
      confidence distribution, a frequentist counterpart to the posterior distribution
      in Bayesian statistics, to obtain optimal confidence regions for the parameters.
      Members of such a region can be generated efficiently via a standard Markov chain
      Monte Carlo algorithm. We then apply this technique to draw inferences about the
      temporal profile of the survival function with censored observations. We
      illustrate the new proposal with the survival data from the well-known Mayo
      primary biliary cirrhosis study and show that the volume of the new 0.95
      confidence region is only one thirty-fourth of that of the conventional
      confidence band.

PMID- 20825393
TI  - Mixed-effects state-space models for analysis of longitudinal dynamic systems.
AB  - The rapid development of new biotechnologies allows us to deeply understand
      biomedical dynamic systems in more detail and at a cellular level. Many of the
      subject-specific biomedical systems can be described by a set of differential or
      difference equations that are similar to engineering dynamic systems. In this
      article, motivated by HIV dynamic studies, we propose a class of mixed-effects
      state-space models based on the longitudinal feature of dynamic systems. State
      space models with mixed-effects components are very flexible in modeling the
      serial correlation of within-subject observations and between-subject variations.
      The Bayesian approach and the maximum likelihood method for standard mixed
      effects models and state-space models are modified and investigated for
      estimating unknown parameters in the proposed models. In the Bayesian approach,
      full conditional distributions are derived and the Gibbs sampler is constructed
      to explore the posterior distributions. For the maximum likelihood method, we
      develop a Monte Carlo EM algorithm with a Gibbs sampler step to approximate the
      conditional expectations in the E-step. Simulation studies are conducted to
      compare the two proposed methods. We apply the mixed-effects state-space model to
      a data set from an AIDS clinical trial to illustrate the proposed methodologies.
      The proposed models and methods may also have potential applications in other
      biomedical system analyses such as tumor dynamics in cancer research and genetic
      regulatory network modeling.

PMID- 20825394
TI  - A spatial dirichlet process mixture model for clustering population genetics
      data.
AB  - Identifying homogeneous groups of individuals is an important problem in
      population genetics. Recently, several methods have been proposed that exploit
      spatial information to improve clustering algorithms. In this article, we develop
      a Bayesian clustering algorithm based on the Dirichlet process prior that uses
      both genetic and spatial information to classify individuals into homogeneous
      clusters for further study. We study the performance of our method using a
      simulation study and use our model to cluster wolverines in Western Montana using
      microsatellite data.

PMID- 20825395
TI  - Likelihood methods for binary responses of present components in a cluster.
AB  - In some biomedical studies involving clustered binary responses (say, disease
      status), the cluster sizes can vary because some components of the cluster can be
      absent. When both the presence of a cluster component as well as the binary
      disease status of a present component are treated as responses of interest, we
      propose a novel two-stage random effects logistic regression framework. For the
      ease of interpretation of regression effects, both the marginal probability of
      presence/absence of a component as well as the conditional probability of disease
      status of a present component, preserve the approximate logistic regression
      forms. We present a maximum likelihood method of estimation implementable using
      standard statistical software. We compare our models and the physical
      interpretation of regression effects with competing methods from literature. We
      also present a simulation study to assess the robustness of our procedure to
      wrong specification of the random effects distribution and to compare finite
      sample performances of estimates with existing methods. The methodology is
      illustrated via analyzing a study of the periodontal health status in a diabetic
      Gullah population.

PMID- 20825396
TI  - Bladder preservation multimodality therapy as an alternative to radical
      cystectomy for treatment of muscle invasive bladder cancer.
AB  - OBJECTIVE: * To evaluate the efficacy of a bladder preservation multimodality
      protocol for patients with operable carcinoma invading bladder muscle. MATERIALS
      AND METHODS: * In this prospective study, we included 33 patients with
      transitional cell carcinoma (TCC) (T2 and T3, Nx, M0) who were amenable to
      complete transurethral resection. * These patients refused radical cystectomy as
      their first treatment option. After maximum transurethral resection of bladder
      tumour (TURBT), all patients received three cycles of adjuvant chemotherapy in
      the form of methotrexate, vinblastin, adriamycin and cisplatin (MVAC) followed by
      radical radiotherapy. * Four weeks later, all cases had radiological and
      cystoscopical re-evaluation. * Complete responders were considered to be those
      patients who had no evidence of residual tumour. All patients were subjected to a
      regular follow-up by cystoscopy and tumour site biopsy conducted every 3 months.
      Abdomino-pelvic computed tomography and chest X-ray were conducted every 6
      months. * The study endpoint was the response to treatment after completion of
      the first year of follow-up after therapy. RESULTS: * Out of 33 eligible
      patients, a total of 28 patients completed the study treatment protocol. Their
      mean +/- SD age was 56.7 +/- 6 years. Trimodal therapy was well tolerated in most
      of cases, with no severe acute toxicities. After 12 months of follow-up, a
      complete response was achieved in 39.3% and a partial response in 7.1%, with an
      overall response rate of 46.4%. * By the end of the first year, disease-free
      survival was reported in 39.3%, whereas 25% were still alive with their disease,
      giving an overall survival of 64.3% for all patients who maintained their intact,
      well functioning bladders. * Tumour stage and completeness of transurethral
      resection of bladder tumour were the most important predictors of response and
      survival. T2 lesions had complete and partial response rates of 69.2% and 23%,
      respectively, whereas T3 lesions had rates of 40% and 13.3%, respectively (P =
      0.001). * The response rate in patients who had complete TURBT was 82.6% vs 20%
      in those with cystoscopic biopsy only (P = 0.001). In addition, disease-free
      survival was 72.7% in T2 patients and 27.3% in T3 patients (P = 0.001).
      CONCLUSION: * In the present study, bladder preservation protocol with MVAC and
      radical radiotherapy achieved suboptimal response rates at 1 year in patients
      with localized TCC invading bladder muscle. Patients with solitary T2 lesions
      that are amenable to complete TURBT achieved the best response rates. Longer
      follow-up is needed to verify these results. Patients with localized disease
      should be encouraged for radical cystectomy, which achieved better results.

PMID- 20825397
TI  - Incidence and survival of patients with carcinoma of the ureter and renal pelvis
      in the USA, 1973-2005.
AB  - OBJECTIVE: * To evaluate epidemiological and survival patterns of upper-tract
      urothelial carcinoma (UTUC) over the past 30 years through a review of a large,
      population-based database. PATIENTS AND METHODS: * Data from the Surveillance,
      Epidemiology and End Results (SEER) database from 1973 to 2005 were reviewed in
      10-year increments to evaluate disease trends. * Univariate and multivariate
      survival analyses identified prognostic variables for outcomes. RESULTS: *In
      total, 13,800 SEER-registered cases of UTUC were included. The overall incidence
      of UTUC increased from 1.88 to 2.06 cases per 100,000 person-years during the
      period studied, with an associated increase in ureteral disease (0.69 to 0.91)
      and a decrease in renal pelvic cancers (1.19 to 1.15). * The proportion of in
      situ tumours increased from 7.2% to 31.0% (P < 0.001), whereas local tumours
      declined from 50.4% to 23.6% (P < 0.001). * There was no change in the proportion
      of patients presenting with distant disease. * In multivariate analysis,
      increasing patient age (P < 0.001), male gender (P < 0.001), black non-Hispanic
      race (P < 0.001), bilateral UTUC (P = 0.001) and regional/distant disease (P <
      0.001) were all associated with poorer survival outcomes. CONCLUSIONS: * The
      incidence of UTUC has slowly risen over the past 30 years. * Increased use of
      bladder cancer surveillance regimens and improved abdominal cross-sectional
      imaging may contribute to the observed stage migration towards more in situ
      lesions. * Although pathological disease characteristics impact cancer outcomes,
      certain sociodemographic factors also appear to portend worse prognosis.

PMID- 20825398
TI  - Androgen substitution with testosterone undecanoate in survivors of bilateral
      testicular cancer requires individually-adjusted injection intervals.
AB  - OBJECTIVES: * To explore the efficacy and safety of testosterone undecanoate (TU)
      (Nebido(r); Bayer Schering Pharma AG, Berlin, Germany) in patients with bilateral
      germ cell testicular cancer (GCTC) who have switched androgen substitution from
      testosterone enanthate (Primoteston Depot(r), Bayer Schering Pharma AG). PATIENTS
      AND METHODS: * In total, 47 bilaterally orchidectomized GCTC patients were
      included in a prospective study to monitor serum gonadal hormones, biochemical
      safety and symptoms of hypogonadism based on the Aging Males' Symptoms scale
      during TU treatment for a 28-week period. RESULTS: * During treatment, serum
      levels of total (TT) and calculated free testosterone (CFT) increased with
      simultaneously decreasing levels of FSH and LH. However, considerable variations
      in median levels of TT and CFT were observed during the study. The highest levels
      of TT and CFT were observed 1-2 weeks after each injection and the lowest
      immediately before the second injection. * Insufficient levels of TT (< 8 nmol/L)
      were observed in 10 patients, with nine of these during the second half of the
      first treatment cycle. Supernormal levels of TT (> 35 nmol/L) were measured in 28
      patients of which 26 occurred at least once during the first 3 weeks of each
      treatment cycle. * A follow-up review at median 39 months after study start
      showed a median steady-state injection interval of 10 weeks, with an individual
      variability of 6-14 weeks. Symptoms according to the Aging Males' Symptoms scale
      remained unchanged. No severe toxicity was encountered. Only one patient
      experienced transient elevation of serum alanine transaminase and aspartate
      transaminase with maximal Common Toxicity Criteria, grade 2. CONCLUSIONS: * TU is
      safe and highly efficient for the treatment of anorchid GCTC survivors. *
      Androgen substitution with TU in bilateral GCTC survivors requires individually
      adjusted injection intervals. In most cases, 10-week intervals appear to be
      sufficient.

PMID- 20825399
TI  - Extended venous thromboembolism prophylaxis after radical pelvic surgery for
      urological cancers.

PMID- 20825400
TI  - Comparison of oncological outcomes of transperitoneal and retroperitoneal
      laparoscopic radical nephrectomy for the management of clear-cell renal cell
      carcinoma: a multi-institutional study.
AB  - OBJECTIVE: * To investigate the oncological efficacy of retroperitoneal
      laparoscopic radical nephrectomy (RLRN) compared with transperitoneal
      laparoscopic radical nephrectomy (TLRN) for the management of clear-cell renal
      cell carcinoma (RCC). PATIENTS AND METHODS: * With emphasis on survival and
      disease recurrence, a retrospective analysis was made of 580 patients who
      underwent TLRN (472 patients) or RLRN (108 patients) at 23 institutions between
      January 1997 and December 2007. * Inclusion criteria were clear-cell RCC, stage
      pT1 to pT2 without any nodal involvement, and metastasis. * Overall survival and
      recurrence-free survival curves were estimated using the Kaplan-Meier method. *
      To assess the association between the surgical approach and survival outcomes,
      Cox proportional hazard models were constructed. RESULTS: * The median follow-up
      was 30 months in the TLRN group and 35.6 months in the RLRN group. Both groups
      were comparable regarding age, gender, body mass index (BMI), Fuhrman's grade,
      size of tumours and stage. * Kaplan-Meier curves and the log-rank test showed no
      significant difference between the TLRN and RLRN groups in 5-year overall (92.6%
      vs 94.5%; P = 0.669) and recurrence-free survival (92.0% vs 96.2%; P = 0.244). *
      In a Cox regression model with age, gender, Eastern Cooperative Oncology Group
      performance status, BMI, nuclear grade and T-stage adjusted variables, no
      significant difference was found between the two surgical approaches. CONCLUSION:
      * The present study is the largest oncological analysis for laparoscopic radical
      nephrectomy (LRN) comparing transperitoneal and retroperitoneal approaches. The
      data from it provide the objective evidence to suggest similar oncological
      outcomes for both approaches to LRN.

PMID- 20825401
TI  - Effect of distraction on the performance of endourological tasks: a randomized
      controlled trial.
AB  - OBJECTIVE: * To establish the effect of distraction on the performance of
      cystoscopy and basic endourological tasks by using a virtual reality (VR)
      simulator. SUBJECTS AND METHODS: * A total of 86 third-year medical students from
      Maastricht University, who had no previous experience in performing the tasks on
      a VR simulator, were randomly assigned to an intervention or control group. * All
      participants performed three endourological tasks on the VR simulator.
      Participants in the intervention group were distracted 1 min into the third task.
      The distraction consisted of being asked to answer questions about a medical case
      that had been presented to all the participants before the hands-on session.
      After two adequate verbal responses the conversation was terminated. * Number of
      traumata, number of missed lesions in the bladder and time to completion were
      measured by the VR simulator. RESULTS: * Number of traumata and missed lesions,
      as well as time to completion were significantly higher in the intervention than
      in the control group with effect sizes (using Cohen's categorization) of 0.48,
      0.41 and 0.50 respectively. * Nevertheless, only 9.5% of the participants in the
      intervention group reported feeling burdened by the distraction. CONCLUSIONS: *
      Distraction during the performance of endourological skills results in
      significantly poorer performance by medical students on all the variables
      measured in a controlled learning environment. * Most students do not realize
      they are affected by distraction. * Further research is needed to determine the
      impact of distraction on more experienced participants and on patient safety.

PMID- 20825402
TI  - Urinary matrix metalloproteinase-7 level is associated with the presence of
      metastasis in bladder cancer.
AB  - OBJECTIVE: * To assess the presence of matrix metalloproteinase (MMP)-7 in urine
      samples of patients with bladder cancer and to investigate the correlation
      between MMP-7 urine concentration and clinicopathological variables. PATIENTS AND
      METHODS: * The presence of MMP-7 in the urine of patients with bladder cancer was
      tested in 32 representative cases using immunoprecipitation followed by western
      blot analysis. * Urinary MMP-7 concentration levels were analyzed in 132 patients
      with bladder cancer and 96 controls using an enzyme-linked immunosorbent assay.
      RESULTS: * MMP-7 levels did not differ significantly between patients with
      localized bladder cancer and controls (P= 0.174). On the other hand, we detected
      a fourfold, significantly elevated MMP-7 concentration in urine samples of
      patients with bladder cancer with regional or distant metastasis (P= 0.003). *
      Using a threshold value of 6.88 ng/ml, determined by receiver-operating
      characteristic curve analysis, a specificity of 82% and a sensitivity of 78% were
      observed. * Western blot analysis revealed that the 55-kDa tissue inhibitor of
      metalloproteinase 1 complexed MMP-7 is the dominant form of urinary matrilysin.
      CONCLUSIONS: * MMP-7 is present in detectable amounts in the urine of patients
      with bladder cancer. Its concentrations are significantly elevated in patients
      with metastatic disease. * Determination of urinary matrilysin level could help
      to detect bladder cancer metastasis, and may therefore provide a more reliable
      prognosis and influence therapy decisions.

PMID- 20825403
TI  - Comparison of lymph node yield in robot-assisted laparoscopic prostatectomy with
      that in open radical retropubic prostatectomy.
AB  - OBJECTIVE: * To investigate both the feasibility and the adequacy of pelvic lymph
      node dissection (PLND) during robot-assisted laparoscopic prostatectomy (RALP) by
      comparing lymph node yields obtained during RALP with those obtained during
      traditional open retropubic radical prostatectomy (RRP). PATIENTS AND METHODS: *
      We retrospectively reviewed 1047 patients who underwent radical prostatectomy
      between 2001 and 2009. * In all, 626 patients underwent RALP while 421 patients
      had traditional open RRP. All patients undergoing bilateral PLND were included in
      our analysis. * Lymph node yields and lymph node involvement for each surgical
      approach were calculated and examined. * PLND-related complications were
      analysed. RESULTS: * Of the 1047 patients, 816 patients underwent bilateral PLND
      of whom 473 underwent RALP, while 343 underwent RRP. The mean lymph node yields
      for the RALP cohort (7.1, interquartile range 4-10) was significantly higher (P <
      0.001) than for the RRP cohort (6.0, interquartile range 3-8). * The percentage
      of patients with nodal involvement was 1.1 for RALP and 2.3 for RRP (P= 0.167). *
      Mean age, preoperative PSA values, and pre- and postoperative Gleason scores were
      similar between the two cohorts. * PLND-related complications were similar
      between both cohorts. CONCLUSIONS: * In patients undergoing RALP, PLND is
      feasible and provides lymph node yields comparable with those of the standard
      open approach. * PLND should be strongly considered in all radical prostatectomy
      patients when clinically indicated, regardless of surgical technique.

PMID- 20825404
TI  - Reconstruction of late-onset transplant ureteral stricture disease.
AB  - OBJECTIVE: * To describe our experience with surgical management of transplant
      ureteral strictures over a 6-year period. PATIENTS AND METHODS: * The present
      study identified patients who underwent open reconstruction for transplant
      ureteral strictures between March 2002 and May 2008 after kidney or kidney
      pancreas transplantation. * Baseline clinical characteristics were documented,
      including age at transplantation and reconstruction, serum creatinine levels,
      immunosuppressive drug regimen, and comorbidities. * Postoperative complications
      were noted, including urinary tract infections, stricture recurrence and graft
      failure. * Successful reconstructions were defined as stable allograft function
      with unobstructed outflow not requiring repeat dilation, ureterotomy or stent
      placement. RESULTS: * Median age at the time of reconstruction was 51 years and
      the mean time from transplantation was 62 months. * Seven of the 13 patients had
      failed previous balloon dilation. * The patients were followed for a median of 41
      months and a successful repair was achieved in 10 of 13 patients. * Ureteral
      strictures recurred in two patients who received ureteroneocystostomies, which
      were subsequently managed with chronic stent exchanges. * Another recurrence
      involved a 1.5-cm anastomotic stricture 6 months postoperatively, which was
      balloon-dilated and has remained recurrence-free for 16 months. CONCLUSIONS: *
      Patients who present > 6 months after renal transplantation with ureteral
      strictures that are recalcitrant to endoscopic management can safely undergo open
      surgical ureteral reconstruction without subsequent renal or graft failure. *
      Further investigation involving a larger patient cohort is required to confirm
      these initial results.

PMID- 20825405
TI  - Dermoscopic features of nonpigmented eccrine poromas in association with their
      histopathological features.
AB  - BACKGROUND: Nonpigmented eccrine poromas (EPs) occasionally mimic various skin
      tumours, but their dermoscopic features have not been clarified. OBJECTIVES: To
      evaluate the dermoscopic features of nonpigmented EPs in association with their
      histopathological features. METHODS: Retrospective analysis of the dermoscopic
      features of 10 histopathologically proven cases of nonpigmented EP at the
      Department of Dermatology, Shinshu University Hospital (Matsumoto, Japan).
      RESULTS: Specific features in vascular structures were observed in five of 10
      nonpigmented EPs. Three cases showed a polymorphous vascular pattern: two cases
      of a combination of hairpin and dotted vessels, and one case of a combination of
      hairpin, dotted and linear-irregular vessels. In addition, there were two cases
      of monomorphous vascular pattern: one case of linear-irregular vessels, and one
      case of hairpin vessels. We did not observe arborizing, crown or comma vessels.
      Comedo-like openings, milia-like cysts, cerebriform pattern and ulceration were
      observed in one case each. Furthermore, nine of 10 cases showed the
      characteristic feature, described as well-circumscribed reddish globule/lacuna
      like structures with separation of mesh bands, which were reminiscent of frog
      eggs aggregation. This characteristic feature on dermoscopy was explained by the
      histopathological features of horizontal sections at a depth of 300-400 MUm from
      the surface. Island-shaped oedematous stroma with numerous microvessels, which
      were surrounded by poroid cells in mesh-like forms, were seen. CONCLUSIONS:
      Vascular structures and 'frog eggs-like appearance' are important features on
      dermoscopic examination of nonpigmented EP. Further studies are required to
      evaluate their diagnostic accuracy to differentiate nonpigmented EP from other
      tumours.

PMID- 20825406
TI  - Allergy-inducing nickel concentration is lowered by lipopolysaccharide at both
      the sensitization and elicitation steps in a murine model.
AB  - BACKGROUND: Nickel (Ni) is the major cause of contact allergy. We previously
      found that lipopolysaccharide (LPS, a cell-surface component of gram-negative
      bacteria) markedly promotes Ni allergy in a murine model. Establishing the
      minimum concentration or amount of Ni needed to induce allergic responses may
      help us to prevent or reduce such responses. OBJECTIVES: Using the above murine
      model, we examined the influence of LPS on the minimum allergy-inducing
      concentrations of Ni (Ni-MAICs) at the sensitization step and at the elicitation
      step. METHODS: BALB/c mice were sensitized by intraperitoneal injection of a
      mixture containing various concentrations of LPS and NiCl(2). Ten days later,
      their ear pinnas were challenged intradermally with a mixture containing various
      concentrations of LPS and NiCl(2), and ear swelling was measured. RESULTS:
      Without LPS, the Ni-MAICs at the sensitization and elicitation steps were around
      1*10(-2) mol L(-1) and 1*10(-5) mol L(-1) , respectively. Sensitization with
      NiCl(2) + LPS did not alter the value at elicitation. Surprisingly, LPS markedly
      reduced these Ni-MAICs (to around 1*10(-6) molL(-1) at sensitization, with 25 MUg
      mL(-1) LPS, and 1*10(-12) mol L(-1) at elicitation, with 0.5 MUg mL(-1) LPS). The
      effect of LPS depended on its concentration and the timing of its injection.
      CONCLUSIONS: Our findings suggest that: (i) Ni-MAIC is higher at sensitization
      than at elicitation; (ii) once sensitization is established, Ni allergy can
      easily be induced by a low concentration of Ni; and (iii) a bacterial milieu or
      infection may greatly facilitate the establishment and elicitation of Ni allergy.

PMID- 20825407
TI  - Cyclosporin and tacrolimus impair insulin secretion and transcriptional
      regulation in INS-1E beta-cells.
AB  - BACKGROUND AND PURPOSE: Introducing the calcineurin inhibitors cyclosporin (CsA)
      and tacrolimus (Tac) has improved the outcome of organ transplants, but
      complications such as new onset diabetes mellitus after transplantation (NODAT)
      decrease survival rates. EXPERIMENTAL APPROACH: We sought, in a beta-cell culture
      model, to elucidate the pathogenic mechanisms behind NODAT and the relative
      contribution of the calcineurin inhibitors. INS-1E cells were incubated at basal
      and stimulatory glucose concentrations, while exposed to pharmacologically
      relevant doses of CsA, Tac and vehicle for 6 or 24 h. RESULTS: Tac inhibited
      basal (P < 0.05), but not glucose-stimulated insulin secretion (GSIS) after 6 h
      of exposure. After 24 h, both agents inhibited basal and GSIS (P < 0.05).
      Calcineurin phosphatase activity was decreased by both drugs during all
      conditions. Apoptosis was only seen with CsA treatment, which also induced a
      slight suppression of calcineurin and insulin mRNA, as well as increased levels
      of the sterol receptor element binding protein (SREBP)-1c, a transcription factor
      thought to suppress genes essential for beta-cell function and induce insulin
      resistance. Expression levels of nuclear factor of activated T-cells (NFAT)-c1, 
      c2, -c3 and -c4 were not decreased notably by either drug. CONCLUSIONS AND
      IMPLICATIONS: Tac had acute inhibitory effects on basal insulin secretion, but
      prolonged exposure (24 h) to Tac or CsA revealed similar suppression of insulin
      secretion. These prolonged effects were mirrored by a total inhibition of
      calcineurin activity in beta-cells. CsA showed greater inhibition of beta-cell
      survival and transcriptional markers, essential for beta-cell function.

PMID- 20825408
TI  - Methylglyoxal scavengers attenuate endothelial dysfunction induced by
      methylglyoxal and high concentrations of glucose.
AB  - BACKGROUND AND PURPOSE: Endothelial dysfunction is a feature of hypertension and
      diabetes. Methylglyoxal (MG) is a reactive dicarbonyl metabolite of glucose and
      its levels are elevated in spontaneously hypertensive rats and in diabetic
      patients. We investigated if MG induces endothelial dysfunction and whether MG
      scavengers can prevent endothelial dysfunction induced by MG and high glucose
      concentrations. EXPERIMENTAL APPROACH: Endothelium-dependent relaxation was
      studied in aortic rings from Sprague-Dawley rats. We also used cultured rat
      aortic and human umbilical vein endothelial cells. The MG was measured by HPLC
      and Western blotting and assay kits were used. KEY RESULTS: Incubation of aortic
      rings with MG (30 uM) or high glucose (25 mM) attenuated endothelium-dependent,
      acetylcholine-induced relaxation, which was restored by two different MG
      scavengers, aminoguanidine (100 uM) and N-acetyl cysteine (NAC) (600 uM).
      Treatment of cultured endothelial cells with MG or high glucose increased
      cellular MG levels, effects prevented by aminoguanidine and NAC. In cultured
      endothelial cells, MG and high glucose reduced basal and bradykinin-stimulated
      nitric oxide (NO) production, cGMP levels, and serine-1177 phosphorylation and
      activity of endothelial NO synthase (eNOS), without affecting threonine-495 and
      Akt phosphorylation or total eNOS protein. These effects of MG and high glucose
      were attenuated by aminoguanidine or NAC. CONCLUSIONS AND IMPLICATIONS: Our
      results show for the first time that MG reduced serine-1177 phosphorylation,
      activity of eNOS and NO production. MG caused endothelial dysfunction similar to
      that induced by high glucose. Specific and safe MG scavengers have potential to
      prevent endothelial dysfunction induced by MG and high glucose concentrations.

PMID- 20825409
TI  - Hydrogen sulphide induces mouse paw oedema through activation of phospholipase
      A2.
AB  - BACKGROUND AND PURPOSE: Hydrogen sulphide (H(2)S), considered as a novel gas
      transmitter, is produced endogenously in mammalian tissue from L-cysteine by two
      enzymes, cystathionine beta-synthase and cystathionine gamma-lyase. Recently, it
      has been reported that H(2)S contributes to the local and systemic inflammation
      in several experimental animal models. We conducted this study to investigate on
      the signalling involved in H(2)S-induced inflammation. EXPERIMENTAL APPROACH: L
      cysteine or sodium hydrogen sulphide (NaHS) was injected into the mouse hind paw
      and oedema formation was evaluated for 60 min. In order to investigate H(2)S
      induced oedema formation, we used 5-HT and histamine receptor antagonists, and
      inhibitors of K(ATP) channels or arachidonic acid cascade. Prostaglandin levels
      were determined in hind paw exudates by radioimmunoassay. Paws injected with L
      cysteine or NaHS were examined by histological methods. KEY RESULTS: Both NaHS
      and L-cysteine caused oedema characterized by a fast onset which peaked at 30
      min. This oedematogenic action was not associated with histamine or 5-HT release
      or K(ATP) channel activation. However, oedema formation was significantly
      inhibited by the inhibition of cyclooxygenases and selective inhibition of
      phospholipase A(2). Prostaglandin levels were significantly increased in exudates
      of hind paw injected with NaHS or L-cysteine. The histological examination
      clearly showed an inflammatory state with a loss of tissue organization following
      NaHS or L-cysteine injection. CONCLUSIONS AND IMPLICATIONS: Phospholipase A(2)
      and prostaglandin production are involved in pro-inflammatory effects of H(2)S in
      mouse hind paws. The present study contributes to the understanding of the role
      of L-cysteine/H(2)S pathway in inflammatory disease.

PMID- 20825410
TI  - Cannabidiol inhibits synaptic transmission in rat hippocampal cultures and slices
      via multiple receptor pathways.
AB  - BACKGROUND AND PURPOSE: Cannabidiol (CBD) has emerged as an interesting compound
      with therapeutic potential in several CNS disorders. However, whether it can
      modulate synaptic activity in the CNS remains unclear. Here, we have investigated
      whether CBD modulates synaptic transmission in rat hippocampal cultures and acute
      slices. EXPERIMENTAL APPROACH: The effect of CBD on synaptic transmission was
      examined in rat hippocampal cultures and acute slices using whole cell patch
      clamp and standard extracellular recordings respectively. KEY RESULTS:
      Cannabidiol decreased synaptic activity in hippocampal cultures in a
      concentration-dependent and Pertussis toxin-sensitive manner. The effects of CBD
      in culture were significantly reduced in the presence of the cannabinoid receptor
      (CB(1) ) inverse agonist, LY320135 but were unaffected by the 5-HT(1A) receptor
      antagonist, WAY100135. In hippocampal slices, CBD inhibited basal synaptic
      transmission, an effect that was abolished by the proposed CB(1) receptor
      antagonist, AM251, in addition to LY320135 and WAY100135. CONCLUSIONS AND
      IMPLICATIONS: Cannabidiol reduces synaptic transmission in hippocampal in vitro
      preparations and we propose a role for both 5-HT(1A) and CB(1) receptors in these
      CBD-mediated effects. These data offer some mechanistic insights into the effects
      of CBD and emphasize that further investigations into the actions of CBD in the
      CNS are required in order to elucidate the full therapeutic potential of CBD.

PMID- 20825412
TI  - Specific detection of pathological three-repeat tau after pretreatment with
      potassium permanganate and oxalic acid in PSP/CBD brains.
AB  - Immunohistochemisty with RD3, a monoclonal antibody specific for three-repeat
      (3R) tau, is sometimes hampered by diffuse neuronal staining on formalin-fixed,
      paraffin-embedded sections pretreated with formic acid and heating. Additional
      pretreatment with potassium permanganate followed by oxalic acid completely
      eliminated this diffuse RD3-immunoreactivity (IR) in neurons. Furthermore, this
      additional pretreatment uniformly enhanced RD3-IR, as well as RD4-IR, a
      monoclonal antibody specific for four-repeat (4R) tau, on pathological deposits
      with tau IR. This enhanced sensitivity and specificity may allow more reliable
      identification of 3R and 4R tau in pathological deposits, which may be variable
      dependent on disease and regions. Cerebral cortex and midbrain from 8 patients [5
      progressive supranuclear palsy (PSP) and 3 corticobasal degeneration (CBD)] were
      screened for RD3- and RD4-IR with this improved procedure. In addition to RD4
      positive structures found both in cerebral cortex and brainstem, RD3-positive
      neurofibrillary tangles (NFTs) were also found in midbrain in 7 of these 8 cases
      but not in the cortex. Multi-labeling study demonstrated that most of RD3
      negative neurons were positive for RD4. This reliable demonstration of
      pathological 3R tau deposits in the brainstem of PSP/CBD, so far presumably
      characterized by deposition of 4R tau, is useful to map tau-positive lesions
      according to their biochemical composition.

PMID- 20825411
TI  - Cilostazol prevents amyloid beta peptide(25-35)-induced memory impairment and
      oxidative stress in mice.
AB  - BACKGROUND AND PURPOSE: Cilostazol may be effective in dementia associated with a
      cerebral ischaemia. In this study, we examined whether it exerts beneficial
      effects on learning and/or memory impairment induced by Abeta(25-35) in mice, and
      compared its effects with those of aspirin. EXPERIMENTAL APPROACH: Abeta(25-35)
      (9 nmol) was administered to mice i.c.v. Learning and memory behaviour were
      evaluated by measuring spontaneous alternation in a Y-maze and a step-down type
      passive avoidance test, on the 5th and 8th days after injection respectively.
      Levels of lipid peroxidation (malondialdehyde) and cytokines in the frontal
      cortex and hippocampus were measured 2, 3, 5 and 7 days after the Abeta(25-35)
      injection. The effects of repeated administration of cilostazol and aspirin (both
      at 30 and 100 mg.kg(-1), p.o.) on any changes induced by Abeta(25-35) were
      evaluated. KEY RESULTS: Repeated administration of cilostazol significantly
      attenuated the impairment of spontaneous alternation and the shortened step-down
      latency induced by Abeta(25-35) . Aspirin did not show any beneficial effect. A
      significant increase in the levels of malondialdehyde (MDA) and IL-1beta (only
      measured in hippocampus) was observed 2, 3 and 5 days after the Abeta(25-35)
      injection in the frontal cortex and hippocampus. Repeated administration of
      cilostazol (100 mg.kg(-1)) completely prevented the increase in MDA levels but
      failed to antagonize the increase in the expression of IL-1beta induced by
      Abeta(25-35). CONCLUSIONS AND IMPLICATIONS: These results suggest that the
      protective effect of cilostazol on Abeta(25-35)-induced memory impairment may be
      related to oxidative stress in the frontal cortex and the hippocampus.

PMID- 20825413
TI  - Role of cytotoxic protease granzyme-b in neuronal degeneration during human
      stroke.
AB  - Infiltration of leukocytes into post-ischemic cerebrum is a well-described
      phenomenon in stroke injury. Because CD-8(+) T-lymphocytes secrete cytotoxic
      proteases, including granzyme-b (Gra-b) that exacerbates post-ischemic brain
      damage, we investigated roles of Gra-b in human stroke. To study the role of Gra
      b in stroke, ischemic and non-ischemic tissues (from post-mortem stroke patients)
      were analyzed using immunoblotting, co-immunoprecipitation, terminal deoxy
      uridine nick end labeling (TUNEL) and Annexin-V immunostaining, and in vitro
      neuron survival assays. Activated CG-SH cells and supernatants were used to model
      leukocyte-dependent injury. Non-ischemic brain tissues were used as non
      pathological controls. Non-activated CG-SH cells and supernatants were used as
      controls for in vitro experiments. Human stroke (ischemic) samples contained
      significantly higher levels of Gra-b and interferon-gamma inducible protein-10
      (IP-10/CXCL10) than non-ischemic controls. In stroke, poly (ADP-ribose)
      polymerase-1 and heat shock protein-70 were cleaved to canonical proteolytic
      "signature" fragments by Gra-b. Gra-b was also found to bind to Bid and caspase
      3. Gra-b also co-localized with Annexin-V(+) /TUNEL(+) in degenerating neurons.
      Importantly, Gra-b inhibition protected both normal and ischemia-reperfused
      neurons against in vitro neurotoxicity mediated by activated CG-SH cells and
      supernatants. These results suggest that increased leukocyte infiltration and
      elevated Gra-b levels in the post-stroke brain can induce contact-dependent and
      independent post-ischemic neuronal death to aggravate stroke injury.

PMID- 20825414
TI  - Expression of C4.4A at the invasive front is a novel prognostic marker for
      disease recurrence of colorectal cancer.
AB  - Metastasis-associated gene C4.4A is a glycolipid-anchored membrane protein
      expressed in several human malignancies. The aim of this study was to explore the
      expression and clinical relevance of C4.4A in colorectal cancer. By quantitative
      RT-PCR, 154 colorectal cancer tissues were examined for C4.4A mRNA. We examined
      132 colorectal cancer tissues by immunohistochemistry using a new polyclonal
      antibody that recognizes the C4.4A protein C-terminus containing the
      glycosylphosphatidyl-inositol anchor signaling sequence. A significant difference
      in 5-year overall survival was found between samples with high and low expression
      of C4.4A mRNA (P = 0.0005). Immunohistochemistry showed strong membranous
      staining of C4.4A at the invasive front of colorectal cancer tumors and at the
      frontier of metastatic lesions to lymph node and lung. The membranous staining
      with enhanced intensity at the invasive front of the primary colorectal cancer
      (Type A: 34/132, 25.6%) was associated with depth of invasion (P = 0.033) and
      venous invasion (P = 0.003), and was a significant independent prognostic factor
      (5-year overall survival in the entire series [n = 132; P = 0.004] and disease
      free survival in stage II and III colorectal cancers [n = 82; P = 0.003]).
      Moreover, Type A C4.4A expression was linked to shorter liver metastasis-free
      survival rate, lung metastasis-free survival rate, or hematogenous metastasis
      free survival (P = 0.0279, P = 0.0061, and P = 0.0006, respectively). Our data
      indicate that expression of the C4.4A protein at the invasive front acts as a
      novel prognostic marker in colorectal cancer, possibly through invasion-related
      mechanisms.

PMID- 20825415
TI  - Differential role of repair proteins, BRCA1/NBS1 and Ku70/DNA-PKcs, in radiation
      induced centrosome overduplication.
AB  - Centrosomes are important cytoplasmic organelles involved in chromosome
      segregation, defects in which can result in aneuploidy, and contribute to
      tumorigenesis. It is known that DNA damage causes the supernumerary centrosomes
      by a mechanism in which centrosomes continue to duplicate during cell cycle
      arrest at checkpoints. We show here that ionizing radiation induces the
      overduplication of centrosomes in a dose-dependent manner, and that the level of
      overduplication is pronounced in BRCA1- and NBS1-deficient cells, even though
      their checkpoint control is abrogated. Conversely, marginal increases in
      overduplication were observed in Ku70- and DNA-PKcs-deficient cells, which are
      intact in checkpoint control. The frequency of radiation-induced overduplication
      of centrosomes might be associated with DNA repair, as it was decreased with
      reduced cell killing after protracted exposures to radiation. As a result, when
      the frequency of radiation-induced centrosome overduplication was plotted against
      radiation-induced cell killing, similar curves were seen for both protracted and
      acute exposures in wild-type cells, Ku70-deficient, and DNA-PKcs-deficient cells,
      indicating a common mechanism for centrosome overduplication. However, the
      absence of either BRCA1 or NBS1 enhanced radiation-induced overduplication
      frequencies by 2-4-fold on the basis of the same cell killing. These results
      suggest that radiation-induced centrosome overduplication is regulated by at
      least two mechanisms: a checkpoint-dependent pathway involved in wild-type cells,
      Ku70-deficient and DNA-PKcs-deficient cells; and a checkpoint-independent pathway
      as observed in BRCA1-deficient and NBS1-deficient cells.

PMID- 20825416
TI  - Global histone acetylation levels: prognostic relevance in patients with renal
      cell carcinoma.
AB  - Epigenetic alterations play an important role in carcinogenesis. Recent studies
      have suggested that global histone modifications are predictors of cancer
      recurrence in various tumor entities. Global histone acetylation levels (histone
      H3 lysine 9 acetylation [H3K9Ac], histone H3 lysine 18 acetylation [H3K18Ac],
      total histone H3 acetylation [H3Ac] and total histone H4 acetylation [H4Ac]) were
      determined in patients with renal cell carcinoma (RCC) using immunohistochemistry
      in a tissue micro array with 193 RCC and 10 oncocytoma specimens. The histone
      acetylation pattern was not different among the diverse histological subtypes of
      RCC or oncocytoma samples. The H3Ac levels were inversely correlated with pT
      stage (P = 0.005), distant metastasis (P = 0.036), Fuhrman grading (P = 0.001)
      and RCC progression (P = 0.029, hazard ratio 0.87). H4Ac deacetylation was
      correlated with pT-stage (P = 0.011) and grading (P = 0.029). H3K18Ac levels were
      an independent predictor of cancer-progression following surgery for localized
      RCC in the univariate (P = 0.001, hazard ratio 0.78) and multivariate (P = 0.005,
      hazard ratio 0.82) analysis. In conclusion, our study supports the concept of
      global histone modification levels as a universal cancer prognosis marker, and
      provides evidence for the use of histone deacetylases inhibitors as future drugs
      in the therapy of RCC.

PMID- 20825417
TI  - Modulation of RIP1 ubiquitylation and distribution by MeBS to sensitize cancer
      cells to tumor necrosis factor alpha-induced apoptosis.
AB  - Overexpression of anti-apoptosis protein cIAP1 due to its genetic amplification
      is found in certain cancers such as esophageal squamous cell carcinoma,
      hepatocellular carcinoma, cervical cancer and lung cancer, and plays a
      significant role in resistance to cancer therapy. We previously reported that a
      class of small molecules represented by (-)-N-[(2S, 3R)-3-amino-2-hydroxy-4
      phenyl-butyryl]-L-leucine methyl ester (MeBS) activates auto-ubiquitylation of
      cIAP1 for proteasomal degradation, and enhances apoptosis of various cancer
      cells. However, the molecular mechanism of how MeBS sensitizes cancer cells to
      apoptosis via downregulation of cIAP1 is not well understood. Here, we show that
      ubiquitylation and distribution of RIP1, a protein ubiquitylated by cIAP1, is
      modulated by MeBS. Upon tumor necrosis factor (TNF)alpha stimulation,
      ubiquitylated RIP1 associates with the TNF-receptor (TNFR) complex, whereas non
      ubiquitylated RIP1 associates with caspase8. MeBS reduces the ubiquitylated RIP1
      in the TNFR complex and increases non-ubiquitylated RIP1 bound to caspase8.
      Downregulation of RIP1 by siRNA reduces apoptosis induced by TNFalpha plus MeBS
      treatment. These results indicate an important role of RIP1 in apoptosis induced
      by combined treatment with TNFalpha and MeBS, suggesting that MeBS sensitizes
      cancer cells to apoptosis by modulating RIP1 ubiquitylation and distribution.

PMID- 20825419
TI  - Role of interleukin-17 in lymphangiogenesis in non-small-cell lung cancer:
      Enhanced production of vascular endothelial growth factor C in non-small-cell
      lung carcinoma cells.
AB  - Interleukin-17 (IL-17), a potent pro-inflammatory cytokine, plays an active role
      in inflammation and cancer. Recently, we found that increased IL-17-producing
      cells correlate with poor survival and increased lymphangiogenesis in non-small
      cell lung cancer (NSCLC), but the mechanism is unknown. Here, we show that IL-17
      promotes lymphangiogenesis via inducing vascular endothelial growth factor-C
      (VEGF-C) production by lung cancer cells. We found that IL-17 receptor (IL-17R)
      is expressed on the surface of Lewis lung carcinoma (LLC) cells but not on
      lymphatic endothelial cells (LEC). Moreover, LEC chemotaxis and tube formation
      (measures of net lymphangiogenic potential) were increased by conditioned medium
      from recombinant mouse IL-17 (rmIL-17)-stimulated LLC but not by rmIL-17.
      Interleukin-17 increased production of VEGF-C in lung cancer cell lines. The
      enhanced chemotaxis and endothelial cord formation in the presence of LLC/rmIL-17
      was inhibited by addition of recombinant mouse VEGF R3/Fc chimera. Treatment of
      the A549 cells with rIL-17 significantly increased VEGF-C expression, which was
      extracellular signal-regulated protein kinase 1/2 (ERK 1/2) dependent.
      Importantly, we found significant correlations between IL-17 expression, VEGF-C
      expression and lymphatic vascular density (LVD) in NSCLC. We conclude that IL-17
      is involved in lymphangiogenesis in NSCLC by enhancing production of VEGF-C, and
      IL-17 may be an important target for the treatment of NSCLC.

PMID- 20825420
TI  - Mechanisms of resistance to anti-human epidermal growth factor receptor 2 agents
      in breast cancer.
AB  - Approximately 20% of breast cancers are characterized by overexpression of human
      epidermal growth factor receptor 2 (HER2) protein and associated gene
      amplification, and the receptor tyrosine kinase is believed to play a critical
      role in the pathogenesis of these tumors. The development and implementation of
      trastuzumab, a humanized monoclonal antibody against the extracellular domain of
      HER2 protein, has significantly improved treatment outcomes in patients with HER2
      overexpressing breast cancer. However, despite this clinical usefulness, unmet
      needs for better prediction of trastuzumab's response and overcoming primary and
      acquired resistance remain. In this review, we discuss several potential
      mechanisms of resistance to trastuzumab that have been closely studied over the
      last decade. Briefly, these mechanisms include: impaired access of trastuzumab to
      HER2 by expression of extracellular domain-truncated HER2 (p95 HER2) or
      overexpression of MUC4; alternative signaling from insulin-like growth factor-1
      receptor, other epidermal growth factor receptor family members, or MET; aberrant
      downstream signaling caused by loss of phosphatase and tensin homologs deleted
      from chromosome 10 (PTEN), PIK3CA mutation, or downregulation of p27; or FCGR3A
      polymorphisms. In addition, we discuss potential strategies for overcoming
      resistance to trastuzumab. Specifically, the epidermal growth factor
      receptor/HER2 tyrosine kinase inhibitor lapatinib partially overcame trastuzumab
      resistance in a clinical setting, so its efficacy results and limited data
      regarding potential mechanisms of resistance to the drug are also discussed.

PMID- 20825421
TI  - Comparison of the GMFM-66 and the PEDI Functional Skills Mobility domain in a
      group of Chinese children with cerebral palsy.
AB  - BACKGROUND: Previous research has suggested there is a high level of
      comparability between the Gross Motor Function Measure-66 (GMFM-66) and the
      Pediatric Evaluation of Disability Inventory (PEDI) Functional Skills Mobility
      domain. However, there are only a few studies that have examined the correlations
      between these instruments. The purpose of this study was to determine the
      correlation between the GMFM-66 and the PEDI Functional Skills Mobility domain
      scaled scores in a group of Chinese children with spastic cerebral palsy, at the
      ages of 12-70 months, in order to explore the feasibility of using them
      interchangeably. METHODS: Secondary data analysis was conducted of data collected
      during a prospective international collaborative study that used the GMFM-66 and
      the PEDI to examine the impact of treatment. This study examined the Pearson
      correlations between the GMFM-66 and the PEDI Functional Skills Mobility domain
      at six time points over the course of 28 consecutive weeks for 115 Chinese
      children who participated at baseline. RESULTS: Pearson correlations between the
      GMFM-66 and the PEDI Functional Skills Mobility domain ranged from 0.83 to 0.90
      for the six time points of data collection, with statistically significant P
      values <0.0001 for each correlation. CONCLUSIONS: These results support previous
      research that the GMFM-66 and the PEDI Functional Skills Mobility domain are
      complementary assessments that may be used interchangeably when it is not
      possible to administer both.

PMID- 20825422
TI  - Symptoms of communication and social impairment in toddlers with congenital heart
      defects.
AB  - BACKGROUND: With the advances in congenital cardiac surgery and medical
      management, mortality rates for congenital heart defects (CHD) have declined
      remarkably. As the number of CHD survivors have increased there is a growing
      focus on developmental morbidity. The objective of the current study is to
      compare symptoms of communication and social impairment in 18-month-old children
      with different severity of CHD with those of controls. METHOD: We linked
      prospective data from the Norwegian Mother and Child Cohort Study, conducted by
      the Norwegian Institute of Public Health, with a nationwide medical CHD registry
      and identified 198 18-month-olds with CHD in a cohort of 47,692. Three groups of
      CHD were distinguished: mild/moderate (n= 122), severe (n= 54) and CHD with
      comorbidity (n= 22). Mothers reported on the child's communication and social
      skills by completing items from the Ages and Stages Questionnaire as part of the
      Norwegian Mother and Child Cohort Study. RESULTS: Children aged 18 months old
      with CHD differed significantly from controls in levels of symptoms of
      communication impairment (P<= 0.0001) and social impairment (P<= 0.0001). The
      largest differences were found in children with CHD and comorbidity. Children
      with severe CHD also showed higher levels of both symptoms of communication and
      social impairment. Children with mild/moderate CHD showed a small difference only
      in symptoms of communication impairment. CONCLUSION: Children with severe CHD and
      CHD with comorbidity show more symptoms of communication and social impairment
      compared with a large cohort at the age of 18 months. It is important to broaden
      the scope of inquiry to involve communication and social developmental domains.

PMID- 20825423
TI  - Cigarette smoking status and recurrent subjective health complaints among US
      school-aged adolescents.
AB  - BACKGROUND: Subjective health complaints are common among adolescents. There is
      evidence that girls are more likely to register complaints than boys. This study
      examines gender differences in the relationship between daily smoking and
      recurrent subjective health complaints in school-aged adolescents in the USA.
      METHODS: A cross-sectional design with a multistage probability sample was used
      to survey 13,339 middle and high school students (grades 6 through 10) with the
      US 2001-2002 Health Behavior in School-Aged Children Survey. RESULTS: Recurrent
      subjective health complaints were higher for adolescents who smoke daily and
      experiment with cigarettes than for those who never smoke. In logistic regression
      analyses, the odds of daily smoking increased twofold for both boys and girls who
      report recurrent irritability/bad temper. For girls, the odds of daily smoking
      were higher among those who reported recurrent headache, stomachache and backache
      compared with never smokers. For boys only recurrent backache and feeling dizzy
      were associated with increased odds of daily smoking. CONCLUSIONS: The
      relationship between recurrent subjective health complaints and daily smoking
      provides new insights into both conditions for school-aged adolescents. Findings
      from this study suggest different patterns of association between daily smoking
      and recurrent subjective health complaints occur for girls and boys. Further
      studies are needed to explore causes and treatment of daily smoking and recurrent
      health complaints among school-aged children.

PMID- 20825424
TI  - Treatment of primary nocturnal enuresis in children: a review.
AB  - Primary nocturnal enuresis is a common childhood disorder. Treatment approaches
      bridge the psychological and medical fields. A substantial body of literature
      addresses the various ways of treating enuresis, from pharmaceuticals to
      behavioural interventions. The medical and psychological literatures have
      proceeded relatively independently from one another and there has been little
      interconnection between the US and international literatures, resulting in a lack
      of discourse and integration among researchers investigating treatment outcomes
      for enuresis. This review examined the evidence base for treatments of primary
      nocturnal enuresis in children. Psychological, pharmaceutical and multi-component
      interventions are discussed. This review sought to provide an integrated
      interdisciplinary and international perspective on treatment efficacy for
      nocturnal enuresis by expressly gathering publications from psychological and
      medical fields, as well as US and international sources. The literature supported
      the urine alarm as the most effective intervention for nocturnal enuresis and
      demonstrated the benefit of combining the urine alarm with other components, both
      behavioural and pharmaceutical. In particular, recent literature showed that the
      urine alarm, when used in conjunction with antidiuretic medication (i.e.
      desmopressin), leads to more dry nights earlier in the conditioning process.
      Disparities between the different literatures were discussed.

PMID- 20825425
TI  - Luteinizing hormone, testosterone and inhibin B levels in the peripubertal period
      and racial/ethnic differences among boys aged 6-11 years: analyses from NHANES
      III, 1988-1994.
AB  - OBJECTIVE: To determine whether the initial physical findings of puberty are
      accompanied by hormonal evidence of pubertal activation of the hypothalamic
      pituitary-gonadal (HPG) axis and whether racial/ethnic differences exist, we have
      analysed hormone levels in relation to age, onset of puberty and race/ethnicity.
      DESIGN: Cross-sectional analysis of luteinizing hormone (LH), testosterone (T)
      and inhibin B from banked sera from a representative sample of US boys aged 6.0
      11.99 years who participated in the National Health and Nutrition Examination
      Survey (NHANES) III. PATIENTS: Eight hundred and twenty-eight boys having sera
      including 228 non-Hispanic white (NHW), 266 non-Hispanic black (NHB), 288 Mexican
      American (MA) and 46 'other'. MEASUREMENTS: Using analysis of variance and linear
      regression techniques, concentrations of LH, T and inhibin B were compared by
      race/ethnicity for all boys and pubertal status (Tanner's Staging 1, 2 and 3+)
      for boys aged 8 years and older. Receiver operating curves were utilized to
      identify cut-points predictive of pubertal HPG status. RESULTS: Mean hormones
      levels progressively increased with age. Receiver operating characteristic (ROC)
      curves indicate hormones are consistent with pubertal onset as indicated by
      Tanner stage 2, except for T and genital stage 2. Inhibin B and LH levels
      increased significantly by genital stage after adjusting for age and
      race/ethnicity, while LH and T concentrations increased significantly across
      pubic hair stages. Levels of inhibin B were significantly higher for NHB boys
      compared with other racial/ethnic groups. CONCLUSIONS: In these cross-sectional
      findings, hormone levels rise gradually as boys approach the peripubertal age,
      whereas an abrupt rise was not associated with the onset of physical changes of
      puberty.

PMID- 20825426
TI  - Physico-chemical features of the environment affect the protein conformation and
      the immunoglobulin E reactivity of kiwellin (Act d 5).
AB  - BACKGROUND: Allergy diagnostic systems sometimes give false positive or negative
      results. In this respect, the influence of protein conformational changes on the
      allergen-IgE interaction sites is worthy to be investigated. OBJECTIVE: To
      investigate the influence of different experimental conditions on the structural
      properties and IgE reactivity of kiwellin (Act d 5) as a model system. METHODS:
      Act d 5 was purified from the natural source. To study its conformational
      features, experiments of circular dichroism (CD) in different media were
      performed. The IgE reactivity was investigated by skin testing, immunoblotting
      and ISAC microarray system, in a population of kiwifruit allergic subjects.
      RESULTS: CD experiments indicated that Act d 5 has a mainly helical structure and
      the conformation is strongly affected by the experimental conditions. The protein
      is more structured in low polarity media and at acidic pH values, similar to
      those of the natural source. Eleven subjects of 29 (38%) allergic to kiwifruit
      were positive to purified natural Act d 5 by skin test. Among them, three
      patients (10%) showed a reaction only to Act d 5 at pH 4.5, and three (10%)
      showed a reaction only to the allergen in standard neutral conditions. No one of
      the 11 subjects with positive skin test recognized Act d 5 immobilized on the
      ISAC system. Eight of nine subjects detected Act d 5 by IgE immunoblotting. One
      subject did not recognize the sequence epitopes of Act d 5 in IgE immunoblotting
      experiments and reacted to the skin test only when the allergen was in acidic
      conditions. CONCLUSIONS AND CLINICAL RELEVANCE: The conformation and IgE
      reactivity of Act d 5 are affected by the physico-chemical characteristics of the
      solvent. These findings suggest that the assay conditions influence the results
      of the diagnostic systems by modulating the pattern of exposed antigenic
      epitopes.

PMID- 20825427
TI  - Production of interleukin-5, -10 and interferon-gamma in cord blood is strongly
      associated with the season of birth.
AB  - BACKGROUND: The effect of labour and different labour-related factors on the cord
      blood (CB) cell cytokine production is still relatively unknown. OBJECTIVE: To
      study the relationships between the production of IL-5, IL-10 and IFN-gamma in CB
      samples and maternal, early neonatal and birth-related factors. METHODS: Whole
      blood samples were collected after birth (n=423) and they were stimulated for 24
      and 48 h with a combination of phorbol ester and ionomycin. Production of IL-5,
      IL-10 and IFN-gamma was determined using ELISA. Maternal, early neonatal and
      birth-related variables were recorded prospectively during pregnancy, and during
      and after delivery. RESULTS: After multivariable adjustment for confounders, the
      strongest predictor of IL-5, IL-10 and IFN-gamma production in CB cell samples
      was the season of birth. Children born in the spring had significantly lower
      cytokine responses compared with those born in the fall. IL-5 production was
      inversely associated with female gender of the child and maternal smoking. If
      corrections for white blood cell (WBC) counts were not performed, IL-5 production
      was also significantly associated with the mode of delivery. Respectively, the
      production of IL-10 and IFN-gamma was inversely associated with prostaglandin
      induction before birth. CONCLUSION: Environmental exposure to pollen and
      ultraviolet irradiation during gestation may have an effect on the cytokine
      profile of the offspring in CB because children born in the spring or winter
      showed the lowest IL-5, IL-10 and IFN-gamma responses. The production of IL-10
      and IFN-gamma was also inversely associated with prostaglandin labour induction
      before birth. Other labour-related factors were not significantly associated with
      production of IL-5, IL-10 and IFN-gamma after WBC count correction.

PMID- 20825429
TI  - Parrot-beak nails.

PMID- 20825428
TI  - Dendritic cell and T cell responses in children with food allergy.
AB  - BACKGROUND: Food allergy (FA) and eosinophilic oesophagitis (EE) are increasingly
      common clinical problems. Dendritic cells (DCs) are key regulators of the
      sensitization and effector phases of allergic immune responses, but their role in
      these diseases is largely unknown. OBJECTIVE: To evaluate for alterations in the
      phenotype and function of DCs in children with IgE-mediated milk allergy or EE
      compared with their non-affected siblings. METHODS: Plasmacytoid DCs (pDCs) and
      myeloid DCs (mDCs) were prepared from peripheral blood of children with milk
      allergy (FA), EE, and non-affected siblings (CON). Purified pDCs and mDCs were
      cultured alone or with autologous CD4(+) lymphocytes. Cytokine levels in plasma,
      or culture supernatants following stimulation, were measured using multiplex
      array immunoassay. Cell-surface molecule expression was determined by flow
      cytometry. RESULTS: DCs from FA subjects produced greater levels of pro
      inflammatory cytokines (IL-6, TNF-alpha), granulocyte macrophage-colony forming
      factor, and mDC-derived IL-10 compared with controls following allergen exposure.
      T(H) 2 but not T(H) 1 cytokines were spontaneously produced in DC-CD4(+) T cell
      co-cultures from children with FA and were not significantly increased after
      stimulation with milk extract, suggesting an ongoing activation in vivo. This
      hypothesis was further supported by evidence for elevated IL-5 and IL-13 protein
      in the plasma of children with both FA and EE. The only significant DC phenotypic
      differences were: (1) reduced levels of CD80 in EE subjects and (2) FcERI
      expression that correlated with serum IgE levels in both groups of subjects.
      CONCLUSION: This study suggests that DCs from children with FA and EE produce
      more pro-inflammatory cytokines, and that their CD4(+) T cells are spontaneously
      activated to produce T(H) 2 cytokines in the presence of FcERI-bearing DCs.

PMID- 20825430
TI  - Blue rubber bleb nevus syndrome: a case report with dermatoscopic features.

PMID- 20825431
TI  - Molecular analysis of Sanfilippo syndrome type C in Spain: seven novel HGSNAT
      mutations and characterization of the mutant alleles.
AB  - The Sanfilippo syndrome type C [mucopolysaccharidosis IIIC (MPS IIIC)] is caused
      by mutations in the HGSNAT gene, encoding an enzyme involved in heparan sulphate
      degradation. We report the first molecular study on several Spanish Sanfilippo
      syndrome type C patients. Seven Spanish patients, one Argentinean and three
      Moroccan patients were analysed. All mutant alleles were identified and comprised
      nine distinct mutant alleles, seven of which were novel, including four missense
      mutations (p.A54V, p.L113P, p.G424V and p.L445P) and three splicing mutations due
      to two point mutations (c.633+1G>A and c.1378-1G>A) and an intronic deletion
      (c.821-31_821-13del). Furthermore, we found a new single nucleotide polymorphism
      (SNP) (c.564-98T>C). The two most frequent changes were the previously described
      c.372-2A>G and c.234+1G>A mutations. All five splicing mutations were
      experimentally confirmed by studies at the RNA level, and a minigene experiment
      was carried out in one case for which no fibroblasts were available. Expression
      assays allowed us to show the pathogenic effect of the four novel missense
      mutations and to confirm that the already known c.710C>A (p.P237Q) is a non
      pathogenic SNP. Haplotype analyses suggested that the two mutations (c.234+1G>A
      and c.372-2A>G) that were present in more than one patient have a common origin,
      including one (c.234+1G>A) that was found in Spanish and Moroccan patients.

PMID- 20825432
TI  - Osteosclerotic bone dysplasia in siblings with a Fam20C mutation.
AB  - Raine syndrome is an autosomal recessive disorder caused by mutations in the
      FAM20C gene. FAM20C codes for the human homolog of DMP4, a dentin matrix protein
      highly expressed in odontoblasts and moderately in bone. DMP4 is probably playing
      a role in the mineralization process. Since the first case reported in 1989 by
      Raine et al. 21 cases have been published delineating a phenotype which
      associates dysmorphic features, cerebral calcifications, choanal atresia or
      stenosis and thoracic/pulmonary hypoplasia. Kan and Kozlowski suggested the name
      of Raine syndrome to describe this new lethal osteosclerotic bone dysplasia. All
      the cases described were lethal during the neonatal period except for the last
      two reported patients aged 8 and 11 years who presented severe mental
      retardation. Here we describe two sisters, with an attenuated phenotype of Raine
      syndrome, who present an unexpectedly normal psychomotor development at ages 4
      and 1, respectively. Identification of a homozygous mutation in the FAM20C gene
      confirmed the Raine syndrome diagnosis, thus contributing to the expansion of the
      Raine syndrome phenotype. This case report also prompted us to revisit the FAM20
      gene classification and allowed us to highlight the ancestral status of Fam20C.

PMID- 20825433
TI  - A guide to interpreting economic studies in infectious diseases.
AB  - Healthcare providers continue to seek improved methods for preventing, detecting
      and treating diseases that affect human survival and quality of life. At the same
      time, there will always be financial constraints because of limited societal
      resources. Many of the discussions on how to provide economically sound solutions
      to this challenge have not fully engaged the input of clinicians in the field.
      The purpose of this review is to increase economic knowledge for clinicians. We
      cover healthcare cost elements and methods used to assign value to a health
      outcome. We outline the challenges in conducting economic studies in the field of
      infectious diseases. Finally, we discuss the meaning of efficiency from multiple
      perspectives, and how the concept of economic externalities applies to infectious
      diseases.

PMID- 20825434
TI  - Costs of healthcare-associated methicillin-resistant Staphylococcus aureus and
      its control.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) clones have caused a huge
      worldwide epidemic of hospital-acquired infections over the past 20-30 years and
      continue to evolve, including the advent of virulent community strains. The
      burden on healthcare services is highly significant, in particular because MRSA
      has not replaced susceptible staphylococcal infection but is an additional
      problem. Treatment strategies for MRSA are suboptimal and compromise the care of
      patients. MRSA is associated with serious morbidity and mortality, both within
      and without hospitals. Although the literature on the costs of MRSA and its
      control is suboptimal, it is clear that the control of MRSA is highly desirable
      and likely to be cost-effective. Any compromises in control are likely to be
      false economies.

PMID- 20825435
TI  - Matrix-assisted laser desorption ionization time-of-flight mass spectrometry:
      usefulness for taxonomy and epidemiology.
AB  - Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass
      spectrometry (MS) is a powerful tool for the species and subspecies
      classification of a broad spectrum of bacteria, including Gram-positive bacteria
      such as Staphylococcus, Streptococcus and Listeria, and Gram-negative bacteria
      such as Neisseria, Salmonella, Aeromonas, Campylobacter and Helicobacter. MALDI
      TOF MS has also been used for the rapid identification and typing of potential
      bioterrorism agents, including Coxiella burnetii, Francisella tularensis and
      Bacillus anthracis.

PMID- 20825436
TI  - Factors associated with severe disease in hospitalized adults with pandemic
      (H1N1) 2009 in Spain.
AB  - The risk factors for complications in patients with influenza A (H1N1)v virus
      infection have not been fully elucidated. We performed an observational analysis
      of a prospective cohort of hospitalized adults with confirmed pandemic influenza
      A (H1N1)v virus infection at 13 hospitals in Spain, between June 12 and November
      10, 2009, to identify factors associated with severe disease. Severe disease was
      defined as the composite outcome of intensive-care unit (ICU) admission or in
      hospital mortality. During the study period, 585 adult patients (median age 40
      years) required hospitalization because of pandemic (H1N1) 2009. At least one
      comorbid condition was present in 318 (54.4%) patients. Pneumonia was diagnosed
      in 234 (43.2%) patients and bacterial co-infection in 45 (7.6%). Severe disease
      occurred in 75 (12.8%) patients, of whom 71 required ICU admission and 13 (2.2%)
      died. Independent factors for severe disease were age <50 years (OR, 2.39; 95%
      CI, 1.05-5.47), chronic comorbid conditions (OR, 2.93; 95% CI, 1.41-6.09), morbid
      obesity (OR, 6.7; 95% CI, 2.25-20.19), concomitant and secondary bacterial co
      infection (OR, 2.78; 95% CI, 1.11-7) and early oseltamivir therapy (OR, 0.32; 95%
      CI 0.16-0.63). In conclusion, although adults hospitalized for pandemic (H1N1)
      2009 suffer from significant morbidity, mortality is lower than that reported in
      the earliest studies. Younger age, chronic comorbid conditions, morbid obesity
      and bacterial co-infection are independent risk factors for severe disease,
      whereas early oseltamivir therapy is a protective factor.

PMID- 20825437
TI  - Gram-negative prosthetic joint infection treated with debridement, prosthesis
      retention and antibiotic regimens including a fluoroquinolone.
AB  - Information is required about treatment outcomes of Gram-negative prosthetic
      joint infections treated with prosthesis retention and surgical debridement,
      especially where biofilm-active antibiotics such as fluoroquinolones are used.
      The outcome of 17 consecutive patients with an early Gram-negative prosthetic
      joint infection who had been treated with prosthesis retention and surgical
      debridement was analysed. Enterobacteriaceae were isolated in 16 patients and
      infections were mixed with other organisms in 13 (76%) patients. The median joint
      age was 17 days and the median duration of symptoms before debridement was 7
      days. All patients initially received intravenous beta-lactam antibiotic therapy
      and 14 patients were then treated with oral ciprofloxacin. Treatment failure
      occurred in two patients over a median period of follow-up of 28 months. In only
      one patient was a relapsed Gram-negative infection responsible for the failure
      and this patient had not been treated with ciprofloxacin. The 2-year survival
      rate free of treatment failure was 94% (95% CI, 63-99%). Prosthesis retention
      with surgical debridement, in combination with antibiotic regimens including
      ciprofloxacin, was effective and should be considered for patients with early
      Gram-negative prosthetic joint infection.

PMID- 20825439
TI  - Diagnosis of prosthetic joint infection by beadmill processing of a
      periprosthetic specimen.
AB  - We report a microbiological process for the documentation of prosthetic joint
      infection (PJI). Intraoperative periprosthetic tissue samples from 92 consecutive
      patients undergoing revision surgery for PJI were submitted to mechanized
      beadmill processing: specimens were aseptically collected in polypropylene vials,
      filled with sterile water and glass beads and submitted to mechanized agitation
      with a beadmill. The documentation rate of PJI following culture on solid and
      liquid media was 83.7% and the contamination rate 8.7%. Final documentation was
      obtained after overnight culture for 51.9% of cases and with 7 days of broth
      culture for all documented cases.

PMID- 20825438
TI  - A multicentre study of antifungal strategies and outcome of Candida spp.
      peritonitis in intensive-care units.
AB  - Information on the species causing Candida peritonitis, their in vitro
      susceptibility, antifungal strategies in this setting and patient outcome is
      still scarce. AmarCand was a prospective, non-interventional study in 271 adult
      intensive-care unit (ICU) patients with proven invasive Candida infection who
      received systemic antifungal therapy (France, 2005-2006). Of these ICU patients,
      93 (median age 65 years, simplified acute physiology score II 52) had Candida
      peritonitis, including 73 nosocomial peritonitis, 53 concomitant bacterial
      peritoneal infections and 26 candidaemias. Candida species were C. albicans (n =
      63/108 isolates, 58%), C. glabrata (n = 22, 20%), C. krusei (n = 9), C. kefyr (n
      = 5), C. parapsilosis (n = 3), C. tropicalis (n = 3), C. ciferii (n = 2) and C.
      lusitaniae (n = 1). Of tested isolates, 28% were fluconazole-resistant or
      susceptible dose-dependent (C. albicans 3/32, C. glabrata 9/14, C. krusei 4/4).
      Empiric antifungal treatment was started 1 day (median) after peritonitis
      diagnosis, with fluconazole (n = 2 patients), caspofungin (n = 12), voriconazole
      (n = 3), amphotericin B (n = 2), or a combination (n = 4). Following
      susceptibility testing, empiric antifungal treatment was judged inadequate in
      9/45 (20%) patients and modified in 30 patients (fluconazole was replaced by
      caspofungin (n = 14) or voriconazole (n = 4)). Mortality in ICU was 38% (35/93)
      and was not influenced by type of Candida species, fluconazole susceptibility,
      time to treatment, candidaemia, nosocomial acquisition, or concomitant bacterial
      infection. No specific factors for death were identified. In summary, a high
      proportion of fluconazole-resistant or susceptible dose-dependent strains was
      cultured. These results confirm the high mortality rates of Candida peritonitis
      and plead for additional investigation in this population. Antifungal treatment
      for severe cases of Candida peritonitis in ICU patients remains the standard
      care.

PMID- 20825440
TI  - Impact of immigration on tuberculosis epidemiology in a low-incidence country.
AB  - Mycobacterium tuberculosis strains from 349 patients were isolated in western
      Sweden during the years 2001-2005. Only 26% of the tuberculosis (TB) patients
      were born in Sweden. All the others were born in any of 42 different countries;
      17% in other European countries, 28% in Africa, 16% in Asia, 11% in the Middle
      East, and 2% in South America. The mean age of the Swedish-born patients was 67
      years, while the mean age among the foreign-born patients was 37 years. The
      male/female ratio was 1.6 among the Swedes and 0.9 among those born abroad.
      Extrapulmonary manifestations of TB were most common among patients born in
      Africa while lung infections without extrapulmonary manifestations were most
      common in patients born in Europe, including Sweden. Spoligotyping showed that
      patients with T or Beijing strains had more pulmonary TB than extrapulmonary TB,
      while patients with EAI and CAS strains had a high proportion of extrapulmonary
      TB. The ancestral and/or evolutionary older PGG1 strains were more often isolated
      from the foreign-born patients than from the Swedish-born patients, who had
      strains generally being of the evolutionary recent genogroups PGG2/PGG3. We
      conclude that immigration from countries with a high incidence of TB has a strong
      impact on the TB epidemiology in western Sweden, a finding that should be taken
      into account by TB control strategists when developing programmes for eradication
      of TB in low prevalence settings.

PMID- 20825441
TI  - A prospective comparison of galactomannan in bronchoalveolar lavage fluid for the
      diagnosis of pulmonary invasive aspergillosis in medical patients under intensive
      care: comparison with the diagnostic performance of galactomannan and of (1-> 3)
      beta-d-glucan chromogenic assay in serum samples.
AB  - Diagnosis of fungal pneumonia (FP) in critically ill patients is challenging.
      Circulating biomarkers for the diagnosis of FP have limitations and the
      combination of different assays in serum samples and directly from the target
      organ may further improve the diagnosis of FP. We prospectively assessed the
      diagnostic utility of paired galactomannan (GM) in bronchoalveolar lavage fluid
      (BAL) and serum GM and (1->3)-beta-D-glucan (BG) assays in critically ill
      patients at risk of FP. Patients with FP were classified according to European
      Organisation for Research and Treatment of Cancer-Mycoses Study Group criteria,
      with modifications. Out of 847 admissions, 51 patients were eligible. There were
      nine invasive aspergillosis (IA) cases (four proven, five probable), three proven
      Pneumocysitis jirovecii pneumonia (PJP) cases and one mixed FP case (probable IA
      and proven PJP). The diagnostic accuracy as given by the area under the receiver
      operating characteristic curve in IA cases (proven and probable) for GM in BAL
      was 0.98 (95% CI, 0.94-1.00), whilst for GM and BG in serum it was 0.85 (95% CI,
      0.74-0.96) and 0.815 (95% CI, 0.66-0.96), respectively. For IA cases (proven and
      probable) AUC for GM in BAL was significantly higher than GM and BG in serum (p
      0.025 and p 0.032, respectively). In one of four proven and one of six probable
      IA cases, GM in serum remained negative, whereas GM in BAL was positive. In
      patients with IA, GM (90%) and BG (80%) appeared a mean of 4.3 days (range, 1-10
      days) before Aspergillus was cultured. GM detection in BAL appears to improve the
      diagnosis of IA in critical patients.

PMID- 20825442
TI  - Matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      identifies 90% of bacteria directly from blood culture vials.
AB  - Matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) is now widely used for marker/multi-biomarker detection in medical
      diagnosis. We tested a new protocol for bacterial identification from blood
      culture broths in hospital routine by using collection tubes with separator gels
      on 503 included samples examined over 3 months, where 1.5 mL was injected by a
      syringe into BD Vacutainer tubes from BACTEC-positive bottles, before processing
      for bacterial protein extraction. Samples were loaded in duplicate onto the MALDI
      MS target, allowing a series of 12 samples to be processed in duplicate within 80
      min by using Biflex III and BioTyper 2.0 software (Bruker). Including
      polymicrobial samples, 193 of 213 of Gram-negative bacteria (91.08%) and 284 of
      319 of Gram-positive bacteria (89.02%) were correctly identified at the species
      level. Enterobacteriaceae constituted 35.15% of all species found,
      Staphylococaceae 37.96%, Streptococaceae and Enterococaceae 20.85%,
      Pseudomonadaceae 1.69%, and anaerobes 2.44%. In most of the polymicrobial
      samples, one of the species present was identified (80.9%). Seven isolates
      remained misidentified as Streptococcus pneumoniae, all belonging to
      Streptococcus mitis. Staphylococcus aureus was identified better when grown on
      anaero-aerobic medium, and MALDI BioTyper identification scores as low as 1.4
      were pertinent, provided that four successive proposals of the same species were
      given. This new protocol correlates with conventional microbiology procedures by
      up to 90%, and by >95% for only monomicrobial samples, and provides a decreased
      turn-around time for identification of bacteria isolated from blood cultures,
      making this technology suitable also for blood cultures, with less delay and cost
      decreases in bacterial diagnostics, and favouring better care of patients.

PMID- 20825443
TI  - Impact of parvovirus B19 infection on paediatric patients with haematological
      and/or oncological disorders.
AB  - To determine the frequency and the impact of parvovirus B19 (B19V) infection and
      its influence on the course of haematological and/or oncological diseases in
      paediatric patients, consecutive serum and bone marrow samples from 110 were
      analyzed for markers of acute, past and persistent B19V-infection using qPCR,
      ELISA and WesternLine. Twenty-seven out of 110 (24.5%) children suffered from non
      malignant diseases (anaemia, pancytopenia, autoimmune disorders); 68/110 (61.8%)
      patients had developed leukaemia, malignant lymphoma or solid malignant tumours;
      15/110 patients (13.6%) presented with other symptoms. At admission, B19V
      specific IgM and IgG indicating acute or previous B19V-infection were observed in
      5 (4.5%) and 48 patients (43.6%), respectively. B19V-DNA (10(3) -10(9)  geq/mL)
      was detectable in serum and/or bone marrow of 22 patients (20.0%). These suffered
      from leukaemia (5), non-Hodgkin lymphoma (2), solid tumours (6), autoimmune (4)
      and haematological (4) disease and fever (1). During clinical observation four
      further leukaemia patients developed viraemia and persistent B19V-infection was
      observed in 13/22 DNA-positive patients. Treatment of B19V-DNA-positive cancer
      patients was associated with more supportive therapy involving erythrocyte and
      thrombocyte transfusion and/or antibiotic therapy. Acute B19V-infection has been
      frequently observed in paediatric patients with haematological and/or oncological
      disease. In patients with non-malignant diseases anaemia or autoimmune disorders
      were diagnosed in association with B19V-infection. Furthermore, a significant
      number of cancer patients displayed markers for acute, recent or persistent B19V
      infection. This association may be strengthened by frequent treatment with blood
      products combined with therapeutic immune suppression. In B19V-infected cancer
      patients supportive therapy was more complex.

PMID- 20825444
TI  - Effects of trophy hunting on lion and leopard populations in Tanzania.
AB  - Tanzania holds most of the remaining large populations of African lions (Panthera
      leo) and has extensive areas of leopard habitat (Panthera pardus), and both
      species are subjected to sizable harvests by sport hunters. As a first step
      toward establishing sustainable management strategies, we analyzed harvest trends
      for lions and leopards across Tanzania's 300,000 km(2) of hunting blocks. We
      summarize lion population trends in protected areas where lion abundance has been
      directly measured and data on the frequency of lion attacks on humans in high
      conflict agricultural areas. We place these findings in context of the rapidly
      growing human population in rural Tanzania and the concomitant effects of habitat
      loss, human-wildlife conflict, and cultural practices. Lion harvests declined by
      50% across Tanzania between 1996 and 2008, and hunting areas with the highest
      initial harvests suffered the steepest declines. Although each part of the
      country is subject to some form of anthropogenic impact from local people, the
      intensity of trophy hunting was the only significant factor in a statistical
      analysis of lion harvest trends. Although leopard harvests were more stable,
      regions outside the Selous Game Reserve with the highest initial leopard harvests
      again showed the steepest declines. Our quantitative analyses suggest that annual
      hunting quotas be limited to 0.5 lions and 1.0 leopard/1000 km(2) of hunting
      area, except hunting blocks in the Selous Game Reserve, where harvests should be
      limited to 1.0 lion and 3.0 leopards/1000 km(2) .

PMID- 20825445
TI  - Founder effects, inbreeding, and loss of genetic diversity in four avian
      reintroduction programs.
AB  - The number of individuals translocated and released as part of a reintroduction
      is often small, as is the final established population, because the
      reintroduction site is typically small. Small founder and small resulting
      populations can result in population bottlenecks, which are associated with
      increased rates of inbreeding and loss of genetic diversity, both of which can
      affect the long-term viability of reintroduced populations. I used information
      derived from pedigrees of four monogamous bird species reintroduced onto two
      different islands (220 and 259 ha) in New Zealand to compare the pattern of
      inbreeding and loss of genetic diversity among the reintroduced populations.
      Although reintroduced populations founded with few individuals had higher levels
      of inbreeding, as predicted, other factors, including biased sex ratio and skewed
      breeding success, contributed to high levels of inbreeding and loss of genetic
      diversity. Of the 10-58 individuals released, 4-25 genetic founders contributed
      at least one living descendent and yielded approximately 3-11 founder-genome
      equivalents (number of genetic founders assuming an equal contribution of
      offspring and no random loss of alleles across generations) after seven breeding
      seasons. This range is much lower than the 20 founder-genome equivalents
      recommended for captive-bred populations. Although the level of inbreeding in one
      reintroduced population initially reached three times that of a closely related
      species, the long-term estimated rate of inbreeding of this one population was
      approximately one-third that of the other species due to differences in carrying
      capacities of the respective reintroduction sites. The increasing number of
      reintroductions to suitable areas that are smaller than those I examined here
      suggests that it might be useful to develop long-term strategies and guidelines
      for reintroduction programs, which would minimize inbreeding and maintain genetic
      diversity.

PMID- 20825446
TI  - Potential misuse of avian density as a conservation metric.
AB  - Effective conservation metrics are needed to evaluate the success of management
      in a rapidly changing world. Reproductive rates and densities of breeding birds
      (as a surrogate for reproductive rate) have been used to indicate the quality of
      avian breeding habitat, but the underlying assumptions of these metrics rarely
      have been examined. When birds are attracted to breeding areas in part by the
      presence of conspecifics and when breeding in groups influences predation rates,
      the effectiveness of density and reproductive rate as indicators of habitat
      quality is reduced. It is beneficial to clearly distinguish between individual-
      and population-level processes when evaluating habitat quality. We use the term
      reproductive rate to refer to both levels and further distinguish among levels by
      using the terms per capita fecundity (number of female offspring per female per
      year, individual level) and population growth rate (the product of density and
      per capita fecundity, population level). We predicted how density and
      reproductive rate interact over time under density-independent and density
      dependent scenarios, assuming the ideal free distribution model of how birds
      settle in breeding habitats. We predicted population density of small populations
      would be correlated positively with both per capita fecundity and population
      growth rate due to the Allee effect. For populations in the density-dependent
      growth phase, we predicted no relation between density and per capita fecundity
      (because individuals in all patches will equilibrate to the same success rate)
      and a positive relation between density and population growth rate. Several
      ecological theories collectively suggest that positive correlations between
      density and per capita fecundity would be difficult to detect. We constructed a
      decision tree to guide interpretation of positive, neutral, nonlinear, and
      negative relations between density and reproductive rates at individual and
      population levels.

PMID- 20825447
TI  - Validity of the prey-trap hypothesis for carnivore-ungulate interactions at
      wildlife-crossing structures.
AB  - Wildlife-exclusion fencing and wildlife-crossing structures (e.g., underpasses
      and overpasses) are becoming increasingly common features of highway projects
      around the world. The prey-trap hypothesis posits that predators exploit crossing
      structures to detect and capture prey. The hypothesis predicts that predation
      events occur closer to a highway after the construction of fences and crossing
      structures and that prey species' use of crossings increases the probability that
      predators will attack prey. We examined interactions between ungulates and large
      carnivores at 28 wildlife crossing structures along 45 km of the Trans-Canada
      Highway in Banff National Park, Alberta. We obtained long-term records of
      locations where ungulates were killed (kill sites) before and after crossing
      structures were built. We also placed remote, motion-triggered cameras at two
      crossing structures to monitor predator behavior following ungulate passage
      through the structure. The proximity of ungulate kill sites to the highway was
      similar before and after construction of fencing and crossing structures. We
      found only five kill sites near crossing structures after more than 32,000 visits
      over 13 years. We found no evidence that predator behavior at crossing structures
      is affected by prey movement. Our results suggest that interactions between large
      mammals and their prey at wildlife-crossing structures in Banff National Park are
      not explained by the prey-trap hypothesis.

PMID- 20825448
TI  - What every conservation biologist should know about economic theory.
AB  - The last century has seen the ascendance of a core economic model, which we will
      refer to as Walrasian economics. This model is driven by the psychological
      assumptions that humans act only in a self-referential and narrowly rational way
      and that production can be described as a self-contained circular flow between
      firms and households. These assumptions have critical implications for the way
      economics is used to inform conservation biology. Yet the Walrasian model is
      inconsistent with a large body of empirical evidence about actual human behavior,
      and it violates a number of basic physical laws. Research in behavioral science
      and neuroscience shows that humans are uniquely social animals and not self
      centered rational economic beings. Economic production is subject to physical
      laws including the laws of thermodynamics and mass balance. In addition, some
      contemporary economic theory, spurred by exciting new research in human behavior
      and a wealth of data about the negative global impact of the human economy on
      natural systems, is moving toward a world view that places consumption and
      production squarely in its behavioral and biophysical context. We argue that
      abandoning the straightjacket of the Walrasian core is essential to further
      progress in understanding the complex, coupled interactions between the human
      economy and the natural world. We call for a new framework for economic theory
      and policy that is consistent with observed human behavior, recognizes the
      complex and frequently irreversible interaction between human and natural
      systems, and directly confronts the cumulative negative effects of the human
      economy on the Earth's life support systems. Biophysical economics and ecological
      economics are two emerging economic frameworks in this movement.

PMID- 20825449
TI  - Use of a business excellence model to improve conservation programs.
AB  - The current shortfall in effectiveness within conservation biology is illustrated
      by increasing interest in "evidence-based conservation," whose proponents have
      identified the need to benchmark conservation initiatives against actions that
      lead to proven positive effects. The effectiveness of conservation policies,
      approaches, and evaluation is under increasing scrutiny, and in these areas
      models of excellence used in business could prove valuable. Typically,
      conservation programs require years of effort and involve rigorous long-term
      implementation processes. Successful balance of long-term efforts alongside the
      achievement of short-term goals is often compromised by management or budgetary
      constraints, a situation also common in commercial businesses. "Business
      excellence" is an approach many companies have used over the past 20 years to
      ensure continued success. Various business excellence evaluations have been
      promoted that include concepts that could be adapted and applied in conservation
      programs. We describe a conservation excellence model that shows how scientific
      processes and results can be aligned with financial and organizational measures
      of success. We applied the model to two well-documented species conservation
      programs. In the first, the Po'ouli program, several aspects of improvement were
      identified, such as more authority for decision making in the field and better
      integration of habitat management and population recovery processes. The second
      example, the black-footed ferret program, could have benefited from leadership
      effort to reduce bureaucracy and to encourage use of best-practice species
      recovery approaches. The conservation excellence model enables greater clarity in
      goal setting, more-effective identification of job roles within programs, better
      links between technical approaches and measures of biological success, and more
      effective use of resources. The model could improve evaluation of a conservation
      program's effectiveness and may be used to compare different programs, for
      example during reviews of project performance by sponsoring organizations.

PMID- 20825450
TI  - Comparing spatially explicit ecological and social values for natural areas to
      identify effective conservation strategies.
AB  - Consideration of the social values people assign to relatively undisturbed native
      ecosystems is critical for the success of science-based conservation plans. We
      used an interview process to identify and map social values assigned to 31
      ecosystem services provided by natural areas in an agricultural landscape in
      southern Australia. We then modeled the spatial distribution of 12 components of
      ecological value commonly used in setting spatial conservation priorities. We
      used the analytical hierarchy process to weight these components and used
      multiattribute utility theory to combine them into a single spatial layer of
      ecological value. Social values assigned to natural areas were negatively
      correlated with ecological values overall, but were positively correlated with
      some components of ecological value. In terms of the spatial distribution of
      values, people valued protected areas, whereas those natural areas
      underrepresented in the reserve system were of higher ecological value. The
      habitats of threatened animal species were assigned both high ecological value
      and high social value. Only small areas were assigned both high ecological value
      and high social value in the study area, whereas large areas of high ecological
      value were of low social value, and vice versa. We used the assigned ecological
      and social values to identify different conservation strategies (e.g.,
      information sharing, community engagement, incentive payments) that may be
      effective for specific areas. We suggest that consideration of both ecological
      and social values in selection of conservation strategies can enhance the success
      of science-based conservation planning.

PMID- 20825451
TI  - Diagnosis of adrenal histoplasmosis by fine needle aspiration cytology: an
      analysis based on five cases.
AB  - BACKGROUND: There is limited description in the literature of the initial
      diagnosis of adrenal histoplasmosis by fine needle aspiration cytology (FNAC).
      OBJECTIVE: To study the aetiology, clinical features and morphological
      differential diagnosis of adrenal histoplasmosis diagnosed initially by FNAC.
      METHODS: Five cases diagnosed by ultrasound-guided FNAC from 2008 to 2010 were
      found in the laboratory records and reviewed. Clinical features and
      cytomorphological features were correlated. RESULTS: All the patients were male
      and were aged 45-83 years (mean 60 years). Three patients had a history of
      contact with birds, one was diabetic and all were negative for human
      immunodeficiency virus (HIV). The commonest symptom was weight loss. On
      cytological smears, uniform round to oval (about 2-4 MUm in diameter) budding
      yeasts were seen intracellularly (within histiocytes) as well as extracellularly.
      In three cases, an inflammatory response in the form of epithelioid cell
      granulomas along with multinucleated giant cells was seen. CONCLUSIONS: Adrenal
      histoplasmosis does occur in immunocompetent persons living in areas not endemic
      for the disease. Although it is not common, it needs to be considered in the
      differential diagnosis of bilateral adrenal enlargement. FNAC is a simple, safe
      technique to establish the initial diagnosis. Correct diagnosis and treatment
      leads to a favourable outcome.

PMID- 20825452
TI  - Retention of mutualism in a geographically diverging interaction.
AB  - A current challenge in coevolutionary biology is to understand how interactions
      between pairs of species change as they diversify into multispecific
      interactions. We tested whether the previously demonstrated pairwise mutualism
      between the widespread pollinating floral parasite Greya politella and its
      Lithophragma hostplants is ecologically enhanced or diminished in a region in
      which another Greya species, Greya obscura, uses the same host, Lithophragma
      cymbalaria. Field surveys and experimental trials showed that pollination
      efficacy by G. politella was more than an order of magnitude higher than by G.
      obscura, but G. politella abundance varied greatly between years. Greya obscura
      had a strongly positive effect on seed set in a year when G. politella densities
      were exceptionally low. Our results suggest that the coevolving mutualism between
      Greya and Lithophragma has potentially been enhanced rather than diminished as
      this interaction has diversified in the number of pollinating Greya species.

PMID- 20825453
TI  - Comparing organic farming and land sparing: optimizing yield and butterfly
      populations at a landscape scale.
AB  - Organic farming aims to be wildlife-friendly, but it may not benefit wildlife
      overall if much greater areas are needed to produce a given quantity of food. We
      measured the density and species richness of butterflies on organic farms,
      conventional farms and grassland nature reserves in 16 landscapes. Organic farms
      supported a higher density of butterflies than conventional farms, but a lower
      density than reserves. Using our data, we predict the optimal land-use strategy
      to maintain yield whilst maximizing butterfly abundance under different
      scenarios. Farming conventionally and sparing land as nature reserves is better
      for butterflies when the organic yield per hectare falls below 87% of
      conventional yield. However, if the spared land is simply extra field margins,
      organic farming is optimal whenever organic yields are over 35% of conventional
      yields. The optimal balance of land sparing and wildlife-friendly farming to
      maintain production and biodiversity will differ between landscapes.

PMID- 20825454
TI  - Virulence of an emerging pathogenic lineage of Vibrio nigripulchritudo is
      dependent on two plasmids.
AB  - Vibrioses are the predominant bacterial infections in marine shrimp farms. Vibrio
      nigripulchritudo is an emerging pathogen of the cultured shrimp Litopenaeus
      stylirostris in New Caledonia and other regions in the Indo-Pacific. The
      molecular determinants of V. nigripulchritudo pathogenicity are unknown; however,
      molecular epidemiological studies have revealed that recent pathogenic V.
      nigripulchritudo isolates from New Caledonia all cluster into a monophyletic
      clade and contain a small plasmid, pB1067. Here, we report that a large plasmid,
      pA1066 (247 kb), can also serve as a marker for virulent V. nigripulchritudo, and
      that an ancestral version of this plasmid was likely acquired prior to other
      virulence-linked markers. Additionally, we demonstrate that pA1066 is critical
      for the full virulence of V. nigripulchritudo in several newly developed
      experimental models of infection. Plasmid pB1067 also contributes to virulence;
      only strains containing both plasmids induced the highest level of shrimp
      mortality. Thus, it appears that these plasmids, which are absent from non
      pathogenic isolates, may be driving forces, as well as markers, for the emergence
      of a pathogenic lineage of V. nigripulchritudo.

PMID- 20825455
TI  - Infantile spasms: toward a selective  diagnostic and therapeutic approach.

PMID- 20825456
TI  - The Japanese scheme of ACTH therapy in  West syndrome.

PMID- 20825458
TI  - Quality of life in a heterogeneous sample of caregivers of cancer patients: an in
      depth interview study.
AB  - To establish the best approach to develop a quality of life (QoL) questionnaire
      for cancer-patient caregivers, this study attempts to identify primary domains of
      QoL in terms of their impact on a purposive sample of caregivers. Seventy-seven
      informal adult caregivers of cancer patients (breast cancer, paediatric
      haematological malignancies or melanoma) with different relationships with the
      patients (parents, children, spouses, siblings, and friends) were recruited at
      three specialised French centres and extensively interviewed. Caregivers' lives
      were altered in several domains: psychological well-being, leisure and everyday
      activities, relationships with institutional caregivers, occupation and finances,
      relationships with family and friends, physical well-being, and relationship with
      the patient. The relative importance of these domains varied mainly in
      association with the caregiver-patient relationship. Multiple correspondence
      analysis identified two isolated clusters: children, and, most significantly,
      friends and siblings. The latter groups emphasised the repercussions on their
      psychological well-being and their relationship with the patient, but were less
      willing to discuss the impact on their relationship with caregivers and on
      occupation, finances, leisure, and everyday activities. This study focuses on the
      caregiver's perspective and advocates the development of a short QoL core
      questionnaire. Additional modules should be cancer-specific or dedicated to
      specifics of the caregiver-patient relationship.

PMID- 20825459
TI  - Coping in men with prostate cancer and their partners: a quantitative and
      qualitative study.
AB  - This study investigated coping and quality of life in men with prostate cancer
      (n= 105, 48-86 years of age) and their partners (n= 85, 48-84 years).
      Participants completed the Abbreviated Dyadic Adjustment Scale, Brief COPE,
      European Organisation for Research and Treatment of Cancer Core Quality of Life
      Questionnaire (QLQ-C30) and open-ended questions on appraisal and coping.
      Multivariate analyses showed that better quality of life was associated with
      higher education levels (role functioning and fatigue), lower avoidant coping
      (emotional, social, and physical functioning and fatigue), and higher
      relationship satisfaction (emotional functioning). Use of medication or combined
      treatments was associated with worse physical and role functioning. Partners
      reported similar quality of life for patients as the patient ratings, except that
      partners reported patients' emotional functioning as significantly worse and
      social functioning as significantly better than the patients' own ratings.
      Patients and partners reported both positive and negative aspects to prostate
      cancer, and mentioned a range of coping strategies. Similarities between patients
      and partners in their responses to prostate cancer were identified using both
      quantitative and qualitative methods. Some differences within dyads were also
      noted and previous suggestions to incorporate partners and significant others in
      education and treatment were supported.

PMID- 20825460
TI  - Splenectomy and surgical cytoreduction in epithelial ovarian cancer: a review.
AB  - Surgical cytoreduction and platinum/taxane combination chemotherapy are the
      mainstay for the treatment of epithelial ovarian cancer patients. In order to
      minimise the tumour mass before chemotherapy, cytoreductive surgery is usually
      performed first. Currently, a splenectomy is included as part of surgical
      cytoreduction in epithelial ovarian cancer, but it is rarely performed. A
      splenectomy is also performed as part of secondary cytoreduction surgery.
      Although there are many reports on surgical techniques, safety and associated
      clinical outcomes of a splenectomy as a standard adjunct of ovarian cytoreductive
      surgery, most evidence is from case(s) reports, with only a few studies. Thus, we
      conducted a review of the literature on this unusual procedure in the context of
      primary and secondary cytoreduction of epithelial ovarian cancer to assess the
      published evidence for its efficacy and safety.

PMID- 20825461
TI  - The reporting of cervical cancer in the mass media: a study of UK newspapers.
AB  - Cervical cancer disproportionately affects those in lower socio-economic groups.
      Mass media, including newspapers, are an important source of information about
      disease and how to prevent it. An analysis of UK national newspaper content
      between 2000 and 2009 is reported, assessing the extent to which information is
      provided about early signs and symptoms, risk factors and ways of preventing
      cervical cancer. The messages in newspapers targeted at readers in lower socio
      economic groups are compared with the messages in other newspapers, and the
      impact of reporting the illness and death of the reality TV star, Jade Goody, on
      the level of medical information contained in articles is assessed. Tabloid or
      'popular' newspapers are found to provide more information about early signs and
      symptoms, and no less information about risk factors, when compared with
      broadsheets or 'serious' papers. This is due to their greater use of personal
      stories of people with cervical cancer. The Jade Goody story was associated with
      an increase in information about early signs and symptoms, and about screening,
      but not (with the exception of the role played by social deprivation) about risk
      factors. Suggestions about how to approach public education via an entertainment
      format in mass media are made.

PMID- 20825462
TI  - Supporting women with intellectual disabilities to access breast cancer
      screening: a healthcare professional perspective.
AB  - Cancer prevention has been identified as the most cost-effective strategy for
      cancer control. This should extend to all groups including women with
      intellectual disability, seeking to access breast cancer screening. The purpose
      of this study was to explore the role of healthcare professionals, such as
      primary healthcare staff (n= 8) and breast care staff (n= 10), on supporting
      women with intellectual disability to access breast screening in one region in
      the UK. A qualitative approach using focus groups and telephone interviews was
      adopted. Healthcare professionals identified that not only was it important that
      women with intellectual disability undergo regular breast screening but that they
      should have the same rights as other women to access breast screening services.
      While many varied risk factors for breast cancer in women with intellectual
      disability were noted, the level of cognitive functioning was clearly
      significant. Barriers to accessing breast screening included literacy problems,
      consent issues and physical health; practical barriers such as transport and
      timing of appointment; and barriers attributed to healthcare professionals,
      including staff attitude and lack of awareness and training. The participants
      identified the need to raise awareness and health promotion education not only
      for the women with intellectual disability but also for healthcare professionals,
      alongside developing more interdisciplinary practice.

PMID- 20825463
TI  - A meta-synthesis of women's symptoms experience and breast cancer.
AB  - The aim of this paper is to examine the symptom experience of women with breast
      cancer using meta-synthesis. Women with breast cancer may experience many
      symptoms resulting from the primary disease and/or treatment of the disease. It
      is very important the overall symptom experience from the patients' perspective
      is captured and understood by health professionals. The question developed was
      'What is the symptom experience of women with breast cancer from time of
      diagnosis to completion of treatment'. The meta-synthesis process as developed by
      Sandelowski and Barroso was used to collect and analyse the data. The overarching
      idea emerging from this meta-synthesis is that the symptoms experience for women
      with breast cancer has effects on the very 'self' of the individual. Emerging is
      women's need to consider the existential issues that they face while
      simultaneously dealing with a multitude of physical and psychological symptoms.
      This meta-synthesis develops a new, integrated, and more complete interpretation
      of findings on the symptom experience of women with breast cancer. The results
      offer the clinician a greater understanding in depth and breadth than the
      findings from individual studies on symptom experiences.

PMID- 20825464
TI  - Sleep and daily functioning during androgen deprivation therapy for prostate
      cancer.
AB  - A limited body of evidence suggests that sleep problems are common in prostate
      cancer patients undergoing androgen deprivation therapy, yet little is known
      about sleep characteristics and the effects of poor sleep on daily functioning in
      this population. This study assessed sleep in 60 prostate cancer patients taking
      androgen deprivation therapy with wrist actigraphy and daily diaries for 7 days.
      The Epworth Sleepiness Scale and the general version of the Functional Assessment
      of Cancer Therapy scale were also administered. On average, total sleep time was
      5.9 (SD = 1.4) h, and sleep efficiency was 75% (SD = 12.0) as assessed by
      actigraphy. There was generally poor concordance between actigraphy and daily
      diary for most sleep metrics. Subjects reported awakening, on average, 2.7 times
      per night, most commonly for nocturia and hot flashes. Assessment of daily
      functioning showed that participants had mild daytime sleepiness, which was
      predicted by total sleep time (F(1,47) = 4.5, P= 0.04) General quality of life
      was not impaired. This study supports more research on the predictors of poor
      sleep in order to identify effective interventions.

PMID- 20825465
TI  - Body mass index is associated with leukotriene inflammation in asthmatics.
AB  - BACKGROUND: Obesity and asthma are characterized by the presence of inflammation.
      Leptin and adiponectin are circulating hormones produced by adipose tissue that
      regulate several metabolic and inflammatory functions. We aimed to determine
      whether obesity influences asthmatic inflammation as well as the contribution of
      leptin or/and adiponectin to a possible linkage between asthmatic and obesity
      related inflammation. MATERIALS AND METHODS: One hundred patients with asthma and
      60 healthy controls were studied. Subjects who had a comorbid illness that could
      interfere with the proposed tests were excluded. All subjects were divided into
      three groups (normal range, pre-obese, obese) according to the criteria of the
      current WHO international classification for body mass index (BMI). Possible
      associations between variables expressing airway inflammation, bronchial hyper
      responsiveness, systemic inflammation and obesity, as assessed by BMI, were
      evaluated. Leptin and adiponectin were also measured and were associated with
      asthma airway and systemic inflammatory variables to elucidate possible
      associations. RESULTS: Obese patients had significant higher values of LTE(4)
      /creatinine in urine compared with pre-obese and normal range ones. In a linear
      regression model, the only significant associations were those between BMI and
      LTE(4) /creatinine in urine. Using the same model, log leptin and log adiponectin
      presented positive and negative associations, respectively with LTE(4)
      /creatinine in urine. No other significant associations were observed in both
      patients and healthy subjects. CONCLUSIONS: In a selected cohort of asthmatic
      patients, obesity is significantly associated with increased urinary leukotriene
      levels. Alterations of leptin/adiponectin balance may be related to the presence
      of leukotriene inflammation in obese asthmatic patients.

PMID- 20825466
TI  - Liver fat in obesity: role of type 2 diabetes mellitus and adipose tissue
      distribution.
AB  - BACKGROUND: Fatty liver is commonly associated with insulin-resistant conditions,
      often related to increased abdominal visceral fat. Our objective was to elucidate
      the specific roles of obesity, type 2 diabetes mellitus, insulin-resistance and
      abdominal fat distribution. MATERIALS AND METHODS: The study population comprised
      13 diabetic obese (DO), 10 nondiabetic obese (NDO), and nine normal-weight
      control (C) men aged 28-65 years, with normal plasma triglyceride levels. DO were
      in good glycaemic control (HbA1c = 6.8 +/- 0.8%) (M +/- SD) with diet (n = 8) or
      diet + metformin (n = 5). Liver fat content was measured by (1) H-magnetic
      resonance spectroscopy, abdominal fat distribution by magnetic resonance imaging
      and insulin sensitivity by hyperinsulinaemic euglycaemic clamp. RESULTS: DO and
      NDO subjects had similar whole-body insulin resistance, BMI and waist
      circumference, higher than those of C subjects (P < 0.001). DO had more liver fat
      (11.9 +/- 7.0%) than NDO (5.2 +/- 2.8%, P < 0.05) and C (1.6 +/- 1.0%, P <
      0.001). Abdominal fat was greater in DO and NDO than in C (visceral: DO 3184 +/-
      843, NDO 2843 +/- 1378 vs. C 1212 +/- 587 cm(3), P < 0.001; subcutaneous: DO 4029
      +/- 362, NDO 5197 +/- 1398 vs. C 2312 +/- 626 cm(3), P < 0.001), visceral fat
      being not significantly different between the two obese groups, and subcutaneous
      fat significantly less in DO than in NDO (P < 0.05). CONCLUSIONS: Type 2 diabetes
      is associated with increased fat accumulation in the liver, independent of
      obesity and whole-body insulin resistance. The increased liver fat in DO patients
      may be part of an altered regional fat distribution that includes an inadequate
      subcutaneous fat storing capacity, rather than simply being a consequence of
      increased abdominal visceral content.

PMID- 20825467
TI  - Increased matrix metalloproteinase activity is associated with migraine and
      migraine-related metabolic dysfunctions.
AB  - OBJECTIVE: Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are
      discussed to be involved in the pathophysiology of migraine. Moreover, MMPs may
      also be involved in migraine-related metabolic alterations like an atherogenic
      lipid profile and hyperinsulinemia. The aim of this study was to investigate the
      impact of MMPs and TIMPs on migraine with and without aura and related metabolic
      dysfunctions. METHODS: MMP activity, six MMPs and three TIMPs, parameters of the
      insulin and lipid metabolism as well as anthropometric parameters were determined
      in 124 non-obese subjects. RESULTS: We found highly significant increased MMP
      activity in migraine patients independent of aura symptoms, which was associated
      with migraine with an odds ratio of 7.57. Interestingly, none of the determined
      MMPs and TIMPs showed significant different serum levels between migraine
      patients and healthy controls. We found significant correlations between MMP
      activity and parameters of the insulin and lipid metabolism, like Homeostasis
      Model Assessment index (HOMA index), cholesterol, triglycerides, and oxidized
      LDL. CONCLUSION: We show here that increased MMP activity is tightly associated
      with migraine and migraine-related hyperinsulinemia and atherogenic lipid
      alterations. Our findings represent a new pathophysiological mechanism, which may
      be of clinical relevance, especially in regard to therapeutic approaches using
      MMP inhibitors.

PMID- 20825468
TI  - Neuromyelitis optica after Japanese encephalitis vaccination.

PMID- 20825469
TI  - Clinically suspected fibrocartilaginous embolism: clinical characteristics,
      treatments, and outcomes.
AB  - OBJECTIVE: To study the frequency, demographics, clinical characteristics, and
      outcomes of patients with an antemortem diagnosis of fibrocartilaginous embolism
      (FCE), a rare cause of spinal cord and cerebral infarction because of the
      presumed embolization of nucleus pulposus material into the vascular circulation.
      METHODS: We retrospectively reviewed the institutional experience of patients who
      received an antemortem diagnosis of FCE by their treating physician at the Mayo
      Clinic (Rochester, MN, USA) from 1997 to 2009. All patients underwent laboratory,
      radiological, and clinical exclusion of other possible and related diagnoses.
      RESULTS: Of 164 patients with acute spinal cord infarction seen during the study
      timeframe, 9 (5.5%; 95% CI 2.5, 10.2%) met inclusion criteria for high likelihood
      of FCE (6 men, 3 women; median age 46 years old, range 21-64). All patients were
      severely affected (median modified Rankin Scale 4, median Barthel index 45; mean
      time to evaluation 57 days). One patient (1/9) experienced concomitant cerebral
      infarction. No patients had noticeable improvement from steroid treatment.
      CONCLUSION: The diagnosis of FCE in life is common at this referral center,
      accounting for 5.5% of all cases of acute spinal cord infarction seen. Although
      FCE is a postmortem diagnosis, we propose clinical criteria for FCE in life to
      better characterize the relatively high number of patients with unexplained
      ischaemic myelopathy.

PMID- 20825470
TI  - Headache, migraine and cardiovascular risk factors: the HUNT study.
AB  - BACKGROUND: Migraine with aura (MA) has been found to be a risk factor for
      cardiovascular disease including ischaemic stroke and myocardial infarction.
      Studies have also reported a higher prevalence of unfavourable cardiovascular
      risk factors amongst migraineurs, but results have been conflicting as to whether
      this is restricted to MA or also holds true for migraine without aura (MO). This
      study aims to examine the relation between headache and cardiovascular risk
      factors in a large cross-sectional population-based study. METHODS: A total of
      48,713 subjects (age >= 20 years) completed a headache questionnaire and were
      classified according to the headache status in the Nord-Trondelag Health Study in
      Norway 1995-1997 (HUNT 2). Framingham 10-year risk for myocardial infarction and
      coronary death could be calculated for 44,098 (90.5%) of these. Parameters
      measured were blood pressure, body mass index, serum total and high-density
      lipoprotein cholesterol. RESULTS: Compared to controls, Framingham risk score was
      elevated in non-migraine headache sufferers (OR 1.17, 95% CI 1.10-1.26),
      migraineurs without aura (OR 1.17, 95% CI 1.04-1.32) and most pronounced amongst
      migraineurs with aura (OR 1.54, 95% CI 1.21-1.95). Framingham risk score
      consistently increased with headache frequency. For non-migrainous headache and
      MO, the increased risk was accounted for by the lifestyle factors smoking, high
      BMI and low physical activity, whilst such factors did not explain the elevated
      risk associated with MA. CONCLUSIONS: Both MA, MO and non-migrainous headache are
      associated with an unfavourable cardiovascular risk profile, but different
      mechanisms seem to underlie the elevated risk in MA than in the other headache
      types.

PMID- 20825471
TI  - An adapted Severity of Dependence Scale is valid for the detection of medication
      overuse: the Akershus study of chronic headache.
AB  - BACKGROUND AND OBJECTIVE: Medication overuse headache is a common subtype of
      chronic headache involving the overuse of simple analgesics, opioids, ergotamine
      or triptans or combinations of these medications. Medication overuse may worsen
      the headache and has been described to have many characteristics similar to
      addiction. The purpose of this study was to validate and optimize the Severity of
      Dependence Scale (SDS) for use amongst people with chronic headache.
      DESIGN/SETTING: In a cross-sectional epidemiological survey, an age- and gender
      stratified sample of 30,000 30- to 44-year-old people were recruited via a posted
      questionnaire. Those with self-reported chronic headache were interviewed by
      neurological residents at Akershus University Hospital, Oslo. Headache was
      classified according to the International Classification of Headache Disorders.
      Split file methodology was employed for data analysis. MAIN OUTCOME MEASURE:
      Severity of Dependence Scale score in those with and without medication overuse.
      RESULTS:   Severity of Dependence Scale score was a significant predictor of
      medication overuse amongst chronic headache patients. Medication overuse could be
      predicted with sensitivity, specificity, positive and negative predictive values
      of 0.79, 0.84, 0.84 and 0.79, respectively, in men and 0.76, 0.77, 0.73 and 0.79
      in women. Linear regression and factor analysis suggested a redundancy for the
      SDS question 'Do you think your use of your headache medication was out of
      control?' Removal of this question improved Chronbach's alpha=0.76. CONCLUSION:
      The SDS is valid for detecting medication overuse and dependency like behaviour
      amongst people with chronic headache. The adapted version may be used to identify
      chronic headache patients who may benefit from detoxification.

PMID- 20825472
TI  - Clinical and genetic evaluation of DYT1 and DYT6 primary dystonia in China.
AB  - BACKGROUND: Dystonia is defined as the presence of sustained involuntary muscle
      contractions, often leading to abnormal posture and movement. DYT1 is caused by a
      mutation in the TOR1A gene, whilst mutations in THAP1 gene have been identified
      as responsible for DYT6. The relative frequency and phenotype differences between
      DYT1 and DYT6 amongst Chinese primary dystonia patients have not been well
      characterized. PATIENTS AND METHODS: One hundred eleven unrelated Chinese
      patients with primary dystonia were screened for mutations in TOR1A and THAP1
      genes, and correlate this with clinical presentation. Exon 5 of TOR1A and all
      three exons and exon-intron conjunctions in THAP1 were screened by direct
      sequencing. RESULTS: Three subjects were found to have the GAG deletion in the
      TOR1A gene, and two patients were detected with THAP1 gene mutations/variations
      (c.224A>T, c.449A>C). The overall mutation frequency was 4.5% in this cohort with
      TOR1A mutations found in 2.7% and THAP1 mutations found in 1.8%. No mutations
      were detected in the controls composed of 100 normal Chinese subjects. The
      clinical presentations of the DYT1 cases included onset in the limbs that could
      progress to the generalized dystonia within several years but without cranial
      involvement. Whilst in the DYT6 cases, the onset was cranial or cervical and
      progresses very slowly. CONCLUSION: The major clinical differences between DYT1
      and DYT6 dystonia in China were the cranial involvement in DYT6 and progress to
      general dystonia within several years in DYT1.

PMID- 20825473
TI  - Plasma total homocysteine and the methylenetetrahydrofolate reductase 677C>T
      polymorphism do not contribute to the distribution of cervico-cerebral
      atherosclerosis in ischaemic stroke patients.
AB  - OBJECTIVE: To evaluate the effects of plasma total homocysteine (tHcyt) and the
      MTHFR 677C>T polymorphism on determining the intracranial- (IC) and extracranial
      (EC) locations of atherosclerosis. METHODS: Brain MR angiography was performed on
      463 patients with symptomatic ischaemic stroke to detect significant
      atherosclerosis (more than 50% stenosis of vessel diameter) in the IC- and EC
      arteries. Relationships between IC- or EC atherosclerosis and plasma tHcyt level
      and/or MTHFR 677C>T genotypes were analyzed after adjusting for vascular risk
      factors. RESULTS: The odd ratios (ORs) of plasma tHcyt were not significantly
      higher in patients with either IC- or EC atherosclerosis than in patients with no
      atherosclerosis. When the study subjects were stratified into three subgroups
      according to their plasma tHcyt levels, neither the crude ORs nor adjusted ORs of
      each IC- and EC atherosclerosis in highest and middle plasma tHcyt tertile were
      significantly different from those in lowest plasma tHcyt tertile. The ORs of the
      MTHFR 677TT genotype in IC- and EC atherosclerosis were not significantly
      different from those in no atherosclerosis. There was no dose-dependent effect of
      MTHFR 677T allele on either IC- or EC atherosclerosis. CONCLUSION: Plasma tHcyt
      level and the MTHFR 677C>T polymorphism do not contribute to the distribution of
      cervico-cerebral atherosclerosis in ischaemic stroke patients.

PMID- 20825476
TI  - Species differences in early patterning of the avian brain.
AB  - The telencephalon is proportionately larger in parrots than in galliformes
      (chicken-like birds), whereas the midbrain tectum is proportionately smaller. We
      here test the hypothesis that the adult species difference in midbrain proportion
      is due to an evolutionary change in early brain patterning. In particular, we
      compare the size of the early embryonic midbrain between parakeets (Melopsittacus
      undulatus) and bobwhite quail (Colinus virgianus) by examining the expression
      domains of transcription factors Pax6 and Gbx2, which are expressed in the
      forebrain and hindbrain, respectively. Because these expression domains form
      rostral and caudal borders with the presumptive midbrain when this region is
      specified (Hamburger-Hamilton stages 9-11), they allow us to measure and compare
      the sizes of a molecularly defined presumptive midbrain in the two species. Based
      on published data from older embryos, we predicted that the molecularly defined
      midbrain territory is significantly larger in quail than parakeets. Indeed, our
      data show that normalized midbrain length is 33% greater in quail and that the
      midbrain to forebrain ratio is 28% greater. This is strong evidence of a
      significant species difference in early brain patterning.

PMID- 20825477
TI  - Females are choosier in the dark: environment-dependent reliance on courtship
      components and its impact on fitness.
AB  - A broad understanding of multimodal courtship function necessitates knowledge of
      the potential information content of signal components, the efficacy of signal
      components in eliciting the appropriate receiver response, and the fitness
      consequences of mating decisions based upon various signal components. We present
      data addressing each of these requirements for the multimodal-signaling wolf
      spider, Schizocosa floridana Bryant. Using diet manipulations, we first
      demonstrate that both visual and seismic courtship signals are condition
      dependent. Next, using high- and low-quantity diet individuals in mate choice
      trials across manipulated signaling environments, we demonstrate that the seismic
      signal is crucial for mating success and further show that female choosiness is
      environment-dependent. Females mated more with high diet males only in the
      absence of visual signals, showing no discrimination in the presence of visual
      signals. Finally, by quantifying the number of offspring produced by our mated
      females, we reveal that a female's mating environment, in conjunction with her
      potential resource availability, influences her fitness-in environments in which
      females exerted choice, heavier females produced more offspring. Together, this
      comprehensive set of experiments demonstrates that female choosiness varies
      across environments, leading to direct fitness consequences.

PMID- 20825478
TI  - Intraspecific reproductive character displacement in a polymorphic poison dart
      frog, Dendrobates pumilio.
AB  - Divergence in male mating signals and associated female preferences is often an
      important step in the process of speciation. Reproductive character displacement,
      the pattern of greater divergence of male signals and/or female preference in
      sympatry than in allopatry, has been observed in a variety of taxa with different
      degrees of postzygotic isolation. A number of selective processes, including
      reinforcement, have been proposed to cause such a pattern. Cases in which
      reproductive character displacement occurs among intraspecific variants are
      especially informative for understanding how selection acting within a species
      can lead to the evolution of reproductive barriers and speciation. This study
      tested the hypothesis that female strawberry poison dart frogs (Dendrobates
      pumilio) in polymorphic populations of the Bocas del Toro archipelago of Panama
      show stronger mating discrimination than do females from monomorphic populations,
      exhibiting an intraspecific pattern of reproductive character displacement. Our
      results contribute important insights into understanding selection's role in
      generating the striking diversity of Bocas del Toro's D. pumilio and provide a
      snapshot of what could be the early stages of reproductive isolation and
      speciation.

PMID- 20825479
TI  - Costly signals in a field cricket can indicate high- or low-quality direct
      benefits depending upon the environment.
AB  - The handicap hypothesis proposes that male signals provide reliable information
      to females because only males of high condition provide high-quality mating
      benefits and can afford the costs of producing attractive signals. In the context
      of direct benefits, the handicap hypothesis predicts that benefit quality and
      signal attractiveness will positively covary among genotypes, positively covary
      among environments, or be affected by congruent genotype-environment
      interactions. The latter should occur if the relative condition of a genotype is
      environment-dependent. We tested these predictions in the variable field cricket,
      Gryllus lineaticeps. An interaction between male family and nutritional
      environment affected the expression of a costly signal preferred by females,
      while only male family affected direct benefit quality. These noncongruent
      effects of family and nutritional environment are inconsistent with the handicap
      hypothesis, and appear to have resulted from variation among nutritional
      environments in the relationship between signal attractiveness and benefit
      quality. Surprisingly, signal attractiveness was positively correlated with
      benefit quality when males experienced a low nutrition environment but negatively
      correlated with benefit quality when males experienced a high nutrition
      environment. As a result, female choice for direct benefits may be difficult,
      particularly in heterogeneous environments, unless females can assess the
      environmental histories of males.

PMID- 20825480
TI  - Gene flow and selection on phenotypic plasticity in an island system of Rana
      temporaria.
AB  - Gene flow is often considered to be one of the main factors that constrains local
      adaptation in a heterogeneous environment. However, gene flow may also lead to
      the evolution of phenotypic plasticity. We investigated the effect of gene flow
      on local adaptation and phenotypic plasticity in development time in island
      populations of the common frog Rana temporaria which breed in pools that differ
      in drying regimes. This was done by investigating associations between traits
      (measured in a common garden experiment) and selective factors (pool drying
      regimes and gene flow from other populations inhabiting different environments)
      by regression analyses and by comparing pairwise F(ST) values (obtained from
      microsatellite analyses) with pairwise Q(ST) values. We found that the degree of
      phenotypic plasticity was positively correlated with gene flow from other
      populations inhabiting different environments (among-island environmental
      heterogeneity), as well as with local environmental heterogeneity within each
      population. Furthermore, local adaptation, manifested in the correlation between
      development time and the degree of pool drying on the islands, appears to have
      been caused by divergent selection pressures. The local adaptation in development
      time and phenotypic plasticity is quite remarkable, because the populations are
      young (less than 300 generations) and substantial gene flow is present among
      islands.

PMID- 20825481
TI  - Horizontal gene transfer and the evolution of bacterial cooperation.
AB  - Bacteria frequently exhibit cooperative behaviors but cooperative strains are
      vulnerable to invasion by cheater strains that reap the benefits of cooperation
      but do not perform the cooperative behavior themselves. Bacterial genomes often
      contain mobile genetic elements such as plasmids. When a gene for cooperative
      behavior exists on a plasmid, cheaters can be forced to cooperate by infection
      with this plasmid, rescuing cooperation in a population in which mutation or
      migration has allowed cheaters to arise. Here we introduce a second plasmid that
      does not code for cooperation and show that the social dilemma repeats itself at
      the plasmid level in both within-patch and metapopulation scenarios, and under
      various scenarios of plasmid incompatibility. Our results suggest that although
      plasmid carriage of cooperative genes can provide a transient defense against
      defection in structured environments, plasmid and chromosomal defection remain
      the only stable strategies in an unstructured environment. We discuss our results
      in the light of recent bioinformatic evidence that cooperative genes are
      overrepresented on mobile elements.

PMID- 20825483
TI  - NMR backbone dynamics studies of human PED/PEA-15 outline protein functional
      sites.
AB  - PED/PEA-15 (phosphoprotein enriched in diabetes/phosphoprotein enriched in
      astrocytes) is a ubiquitously expressed protein and a key regulator of cell
      growth and glucose metabolism. PED/PEA-15 mediates both homotypic and heterotypic
      interactions and is constituted by an N-terminal canonical death effector domain
      and a C-terminal tail. In the present study, the backbone dynamics of PED/PEA-15
      via (15)N R(1) and R(2) and steady-state [(1)H]-(15)N NOE measurements is
      reported. The dynamic parameters were analyzed using both Lipari-Szabo model-free
      formalism and a reduced spectral density mapping approach. The results obtained
      define a polar and charged surface of the death effector domain characterized by
      internal motions in the micro- to millisecond timescale, which is crucial for the
      multiple heterotypic functional protein-protein interactions in which PED/PEA-15
      is involved. The present study contributes to a better understanding of the
      molecular basis of the PED/PEA-15 functional interactions and provides a more
      detailed surface for the design and development of PED/PEA-15 binders.

PMID- 20825482
TI  - Enzymatic control of anhydrobiosis-related accumulation of trehalose in the
      sleeping chironomid, Polypedilum vanderplanki.
AB  - Larvae of an anhydrobiotic insect, Polypedilum vanderplanki, accumulate very
      large amounts of trehalose as a compatible solute on desiccation, but the
      molecular mechanisms underlying this accumulation are unclear. We therefore
      isolated the genes coding for trehalose metabolism enzymes, i.e. trehalose-6
      phosphate synthase (TPS) and trehalose-6-phosphate phosphatase (TPP) for the
      synthesis step, and trehalase (TREH) for the degradation step. Although
      computational prediction indicated that the alternative splicing variants
      (PvTpsalpha/beta) obtained encoded probable functional motifs consisting of a
      typical consensus domain of TPS and a conserved sequence of TPP, PvTpsalpha did
      not exert activity as TPP, but only as TPS. Instead, a distinct gene (PvTpp)
      obtained expressed TPP activity. Previous reports have suggested that insect TPS
      is, exceptionally, a bifunctional enzyme governing both TPS and TPP. In this
      article, we propose that TPS and TPP activities in insects can be attributed to
      discrete genes. The translated product of the TREH ortholog (PvTreh) certainly
      degraded trehalose to glucose. Trehalose was synthesized abundantly, consistent
      with increased activities of TPS and TPP and suppressed TREH activity. These
      results show that trehalose accumulation observed during anhydrobiosis induction
      in desiccating larvae can be attributed to the activation of the trehalose
      synthetic pathway and to the depression of trehalose hydrolysis.

PMID- 20825484
TI  - The effect of zinc oxide nanoparticles on the structure of the periplasmic domain
      of the Vibrio cholerae ToxR protein.
AB  - Proteins adsorbed on nanoparticles (NPs) are being used as biosensors and in drug
      delivery. However, our understanding of the effect of NPs on the structure of
      proteins is still in a nascent state. In this work we report the unfolding
      behavior of the periplasmic domain of the ToxR protein (ToxRp) of Vibrio cholerae
      on zinc oxide (ZnO) nanoparticles with a diameter of 2.5 nm. This protein plays a
      crucial role in regulating the expression of several virulence factors in the
      pathogenesis of cholera. Thermodynamic analysis of the equilibrium of unfolding,
      induced both by urea and by guanidine hydrochloride (GdnHCl), and measured by
      fluorescence spectroscopy, revealed a two-state process. NPs increased the
      susceptibility of the protein to denaturation. The midpoints of transitions for
      the free and the NP-bound ToxRp in the presence of GdnHCl were 1.5 and 0.5 m
      respectively, whereas for urea denaturation, the values were 3.3 and 2.4 m,
      respectively. Far-UV CD spectra showed a significant change in the protein
      conformation upon binding to ZnO NPs, which was characterized by a substantial
      decrease in the alpha-helical content of the free protein. Isothermal titration
      calorimetry, used to quantify the thermodynamics of binding of ToxRp with ZnO
      NPs, showed an exothermic binding isotherm (DeltaH = -9.8 kcal.mol(-1) and DeltaS
      = -5.17 cal.mol(-1).K(-1)).

PMID- 20825487
TI  - Changes in arterial stiffness during continued infliximab treatment in patients
      with inflammatory arthropathies.
AB  - Chronic inflammatory arthropathies such as rheumatoid arthritis (RA), ankylosing
      spondylitis (AS), and psoriatic arthritis (PsA) are associated with an increased
      risk of cardiovascular disease. TNF-alpha antagonists may improve vascular
      function in these patients and thus be beneficial with regard to cardiovascular
      disease. This study evaluated arterial stiffness and disease activity between two
      infusions with a TNF-alpha antagonist (infliximab) in patients with inflammatory
      arthropathies on long-term infliximab therapy. Augmentation index (AIx), aortic
      pulse wave velocity (aPWV), and disease activity were measured in 17 patients
      with RA, AS, or PsA who had been treated with infliximab for at least 12 months.
      The patients were examined immediately before their infliximab infusion and
      thereafter every 10th day until their next infusion scheduled at week 4-8. AIx
      and aPWV did not change during the period between two infliximab infusions. The
      patients had a temporary improvement in the general disease activity assessed on
      visual analogue scales by the patients (P = 0.04) and the investigator (P = 0.02)
      after the infusion. In the group of patients with RA, the Disease Activity Score
      (DAS28) changed significantly in a similar manner (P = 0.003). C-reactive protein
      and erythrocyte sedimentation rate remained unchanged. Infliximab infusions did
      not alter aortic pulse wave velocity or augmentation index in patients with
      inflammatory arthropathies who were on long-term infliximab therapy. Reductions
      in the general disease activity and DAS28 were not reflected in alterations of
      aortic stiffness or augmentation index.

PMID- 20825488
TI  - QT interval prolongation: prevalence, risk factors and pharmacovigilance data
      among methadone-treated patients in France.
AB  - Several reports have suggested the role of methadone in QT prolongation, Torsades
      de Pointes (TdP), and ventricular arrhythmia. The aim of this study was to
      identify the frequency of QT interval prolongation and QT dispersion among a
      population of addict patients treated with methadone, completed by the
      description of cardiac events reported to the French pharmacovigilance system. QT
      interval (corrected with the Bazett's method) and dispersion were measured on a
      cohort of patients treated with methadone during their visit to addiction
      specialized centers in Southwest of France. Whenever possible, methadone blood
      concentrations were measured. In addition, reports concerning methadone were
      searched in the French Pharmacovigilance database from 1996 to 2007. The cohort
      included 42 patients with mean QTc length of 414.3 +/- 28.5 ms and mean QT
      dispersion of 66.0 +/- 41.1 ms. None of the patient presented a QTc above 500 ms.
      These values were higher in patients with recent increase in methadone dose, use
      of tobacco or drugs prolonging QT, and history of cardiac disease. We found five
      cases of QT prolongation (3 TdP) and seven cases of sudden deaths in the French
      pharmacovigilance database (2.2% of methadone reports). Most of these events
      occurred after introducing methadone or another drug potentially interacting with
      methadone. Methadone can prolong the QT interval at dose usually used for
      addiction maintenance treatment in France. A cardiac evaluation, with at least a
      systematic ECG, could be useful during methadone treatment, particularly in case
      of recent modification of the regimen.

PMID- 20825489
TI  - Relationships between plasma concentrations of morphine, morphine-3-glucuronide,
      morphine-6-glucuronide, and intravenous morphine titration outcomes in the
      postoperative period.
AB  - Although intravenous morphine titration (IMT) is widely used to control moderate
      to severe postoperative pain, the relationships between plasma concentrations of
      morphine and its metabolites, morphine-3-glucuronide (M3G) and morphine-6
      glucuronide (M6G), and IMT outcomes in the postanesthesia care unit (PACU) have
      not been yet investigated. IMT was administrated as a bolus of 2 or 3 mg every 5
      min. Titration was interrupted in case of pain relief (visual analog score <=30),
      adverse events, sedation, or failure of morphine titration. Blood samples were
      collected at the end of morphine titration to determine plasma concentration of
      morphine and its two metabolites. Data from 214 patients were analyzed; 143 (67%)
      of the patients achieved complete pain relief, 39 (18%) experienced adverse
      events, and 32 (15%) failure of morphine titration. At the end of titration,
      there were no significant differences in morphine, M6G, M3G concentrations
      between sedated and nonsedated patients (32 vs. 42 ng/mL (P = 0.07), 38 vs. 45
      ng/mL (P = 0.51), 300 vs. 342 ng/mL (P = 0.29), respectively), or patients with
      or without adverse events (40 vs. 41 ng/mL (P = 0.95), 37 vs. 46 ng/mL (P =
      0.51), 287 vs. 340 ng/mL (P = 0.72), respectively). Our study demonstrated a lack
      of relationship between plasma concentrations or ratios of morphine, M3G, and
      M6G, with IMT outcomes in PACU. This result suggests that the kinetics of
      morphine and its metabolites have limited value for explaining clinical effects
      of morphine in this clinical setting.

PMID- 20825490
TI  - Pleiotropic effects of the 11p13 locus on developmental verbal dyspraxia and EEG
      centrotemporal sharp waves.
AB  - We recently showed genomewide linkage of centrotemporal sharp waves (CTS) in
      classic Rolandic epilepsy (RE) families to chromosome 11p13, and fine-mapped this
      locus to variants in the ELP4 gene. Speech sound disorder (SSD) is a common
      comorbidity in RE subjects, of unknown etiology, which co-aggregates in family
      members in a manner that could hypothetically be explained by shared underlying
      genetic risk with CTS. Furthermore, the neural mechanism of SSD is unknown,
      although individuals with rare, Mendelian forms of RE are described with severe
      verbal and oromotor apraxia. We therefore first performed genomewide linkage
      analysis for SSD, operationally defined as clinical history consistent with ICD
      10 speech articulation disorder, in 38 families singly ascertained through a
      proband with RE. We tested the hypothesis of shared genetic risk with CTS at the
      11p13 locus. In the second part of the study we used computerized acoustic
      analysis of recorded speech to test the hypothesis of dyspraxia as a mechanism
      for SSD in a smaller subset of RE probands and relatives. In two-point and
      multipoint LOD score analysis, we found that evidence for linkage to the 11p13
      locus increased substantially when the phenotype was broadened from CTS to
      CTS/SSD. In multipoint analysis, the LOD score rose by 3.2 to HLOD 7.54 at
      D11S914 for CTS/SSD, the same marker at which multipoint linkage maximized for
      CTS alone. Non-parametric, affected-only methods in a sub-set of the data provide
      further confirmatory evidence for pleiotropy. In acoustic analysis there were
      voice-onset time abnormalities in 10/18 RE probands, 8/16 siblings and 5/15
      parents, providing evidence of breakdown in the spatial/temporal properties of
      speech articulation consistent with a dyspraxic mechanism. The results from
      genetic and physiological studies suggest a pleiotropic role for the 11p13 locus
      in the development of both SSD and CTS, and also indicate a dyspraxic mechanism
      for the SSD linked to 11p13. Taken together, these data strongly support a
      neurodevelopmental origin for classic RE.

PMID- 20825491
TI  - Up-regulation of PSF1 promotes the growth of breast cancer cells.
AB  - PSF1 is a subunit of the GINS complex that functions along with the MCM2-7
      complex and Cdc45 in eukaryotic DNA replication. Although mammalian PSF1 is
      predominantly expressed in highly proliferating cells and organs, little is known
      about the roles of PSF1 in mature cells or cancer cells. We found that PSF1 was
      expressed at relatively high levels in breast tumor cells, but at low levels in
      normal breast cells. Knockdown of PSF1 expression using small interfering RNA
      (siRNA) slowed the growth of breast cancer cell lines by delaying DNA replication
      but did not affect proliferation of normal human mammary epithelial cells.
      Reduced PSF1 expression also inhibited anchorage-independent growth in breast
      cancer cell lines. These results suggest that PSF1 over-expression is
      specifically involved in breast cancer cell growth. Therefore, PSF1 inhibition
      might provide new therapeutic approaches for breast cancer.

PMID- 20825492
TI  - ERK1 and ERK2 are required for radial glial maintenance and cortical lamination.
AB  - ERK1/2 is involved in a variety of cellular processes during development, but the
      functions of these isoforms in brain development remain to be determined. Here,
      we generated double knockout (DKO) mice to study the individual and combined
      roles of ERK1 and ERK2 during cortical development. Mice deficient in Erk2, and
      more dramatically in the DKOs, displayed proliferation defects in late radial
      glial progenitors within the ventricular zone, and a severe disruption of
      lamination in the cerebral cortex. Immunohistochemical analyses revealed that
      late-generated cortical neurons were misplaced and failed to migrate the upper
      cortical layers in DKO mice. Moreover, these mice displayed fewer radial glial
      fibers, which provide architectural guides for radially migrating neurons. These
      results suggest that extracellular signal-regulated kinase signaling is essential
      for the expansion of the radial glial population and for the maintenance of
      radial glial scaffolding. Tangential migration of interneurons and
      oligodendrocytes from the ganglionic eminences (GE) to the dorsal cortex was more
      severely impaired in DKO mice than in mice deficient for Erk2 alone, because of
      reduced progenitor proliferation in the GE of the ventral telencephalon. These
      data demonstrate functional overlaps between ERK1 and ERK2 and indicate that
      extracellular signal-regulated kinase signaling plays a crucial role in cortical
      development.

PMID- 20825493
TI  - Loss of circadian rhythm and light-induced suppression of pineal melatonin levels
      in Cry1 and Cry2 double-deficient mice.
AB  - Cryptochrome 1 and 2 (Cry1 and Cry2) are considered essential for generating
      circadian rhythms in mammals. The role of Cry1 and Cry2 in circadian rhythm
      expression and acute light-induced suppression of pineal melatonin was assessed
      using Cry1 and Cry2 double-deficient mice (Cry1(-/-) /Cry2(-/-) ) developed from
      the C3H strain that synthesizes melatonin. We examined the circadian variation of
      pineal melatonin under a 12:12-h light-dark (LD) cycle and constant darkness
      (DD). Light suppression of pineal melatonin concentration was analyzed by
      subjecting a 30-min light pulse at the peak phase of melatonin concentration.
      Wild-type mice showed significant rhythmicity in pineal melatonin concentration
      with the highest level at Zeitgeber time 22 (ZT22, where time of light on was
      defined as ZT0) under LD or ZT18 on the first day of DD. In contrast, Cry1(-/-)
      /Cry2(-/-) mice did not show significant circadian rhythmicity, with only a small
      peak observed at ZT22 in LD. Nevertheless, a significant daily variation could be
      observed under DD, with a small increase at ZT6 and ZT18 h. Melatonin
      concentration was significantly suppressed by acute light pulse at ZT22 in wild
      type mice but not in Cry1(-/-) /Cry2(-/-) mice. The present results suggest that
      Cry genes are required for regulating pineal melatonin synthesis via circadian
      and photic signals from the suprachiasmatic nucleus of the hypothalamus (SCN).

PMID- 20825494
TI  - Purvalanol A, a CDK inhibitor, effectively suppresses Src-mediated transformation
      by inhibiting both CDKs and c-Src.
AB  - The nonreceptor tyrosine kinase c-Src is frequently over-expressed or
      hyperactivated in various human cancers and contributes to cancer progression in
      cooperation with up-regulated growth factor receptors. However, Src-selective
      anticancer drugs are still in clinical trials. To identify more effective
      inhibitors of c-Src-mediated cancer progression, we developed a new screening
      platform using Csk-deficient cells that can be transformed by c-Src. We found
      that purvalanol A, developed as a CDK inhibitor, potently suppressed the
      anchorage-independent growth of c-Src-transformed cells, indicating that the
      activation of CDKs contributes to the c-Src transformation. We also found that
      purvalanol A suppressed the c-Src activity as effectively as the Src-selective
      inhibitor PP2, and that it reverted the transformed morphology to a nearly normal
      shape with less cytotoxicity than PP2. Purvalanol A induced a strong G2-M arrest,
      whereas PP2 weakly acted on the G1-S transition. Furthermore, when compared with
      PP2, purvalanol A more effectively suppressed the growth of human colon cancer
      HT29 and SW480 cells, in which Src family kinases and CDKs are activated. These
      findings demonstrate that the coordinated inhibition of cell cycle progression
      and tyrosine kinase signaling by the multi-selective purvalanol A is effective in
      suppressing cancer progression associated with c-Src up-regulation.

PMID- 20825495
TI  - Cyclin-dependent kinase promotes formation of the synaptonemal complex in yeast
      meiosis.
AB  - Cyclin-dependent protein kinases (CDKs) are required for various cell cycle
      events both in mitosis and in meiosis. During the meiotic prophase of
      Saccharomyces cerevisiae, only one CDK, Cdc28, which forms a complex with B-type
      cyclins, Clb5 or Clb6, promotes not only the onset of premeiotic DNA replication
      but also the formation of meiotic double-strand breaks (DSBs). In this study, we
      showed that Cdc28 exhibits punctate staining on chromosomes during meiotic
      prophase I. Chromosomal localization of Cdc28, dependent on Clb5 and/or Clb6, is
      frequently observed in zygotene and pachytene, when formation of the synaptonemal
      complex (SC) occurs. Interestingly, the CDK localization is independent of DSB
      formation, but rather dependent on meiosis-specific chromosome components such as
      Red1, Hop1 and a cohesin subunit Rec8. Compromised CDK activity in meiotic
      prophase leads to defective SC formation without affecting DSB formation. These
      results suggest that CDK-dependent phosphorylation regulates meiotic chromosome
      morphogenesis.

PMID- 20825496
TI  - Donepezil treatment in Alzheimer's disease patients with and without
      cerebrovascular lesions: a preliminary report.
AB  - AIM: Donepezil has not been evaluated in Korean patients with Alzheimer's disease
      (AD) for up to 1 year. The objectives of this study were to evaluate the
      differential efficacy of donepezil in Korean AD patients with and without
      concomitant cerebrovascular lesions (CVL). METHODS: This study was a 48-week open
      label trial of donepezil in patients with probable AD of mild to moderate
      severity. CVL were evaluated through magnetic resonance imaging (MRI) findings
      within 3 months. Efficacy analyses were performed for cognitive, behavioral and
      functional outcome measures. RESULTS: Concomitant CVL were documented in 35
      (30.7%) of the patients on MRI. Seventy-nine (69.3%) of the patients were
      considered not to have concomitant CVL. The mean Mini-Mental State Examination
      scores of both patients with and without CVL showed improvement at each
      evaluation. However, there was no statistical difference in improvement between
      the groups. CONCLUSION: The presence of CVL should not deter clinicians from
      treating AD with donepezil.

PMID- 20825497
TI  - Effect of accelerated ageing and surface sealing on the permanent deformation of
      auto-polymerising soft linings.
AB  - PURPOSE: To compare the effects of different ageing methods on the permanent
      deformation of two permanent soft liners. MATERIALS AND METHODS: The materials
      selected were auto-polymerising acrylic resin and silicone-based reliners. Sealer
      coating was also evaluated. Sixty specimens of each reliner were manufactured
      (12.7 mm diameter and 19 mm length). Specimens were randomly distributed into 12
      groups (n = 10) and submitted to one of the accelerated ageing processes.
      Permanent deformation tests were conducted with a mechanical device described
      within the American Dental Association specification number 18 with a compressive
      load of 750 gf applied for 30 s. All data were submitted for statistical
      analysis. Mann-Whitney test compared the effect of the surface sealer on each
      material and the permanent deformation of the materials in the same ageing group
      (p = 0.05). Kruskal-Wallis and Dunn tests compared all ageing groups of each
      material (p = 0.05). RESULTS: The silicone-based reliner presented a lower
      permanent deformation than the acrylic resin-based reliner, regardless of the
      ageing procedure. The surface sealer coating was effective only for the
      thermocycled silicone group and the accelerated ageing processes affected only
      the permanent deformation of the acrylic resin-based material. CONCLUSION: The
      silicone-based reliner presented superior elastic properties and the
      thermocycling was more effective in ageing the materials.

PMID- 20825498
TI  - Evaluation of understanding levels of Indian dental students' knowledge and
      perceptions regarding older adults.
AB  - Increasing numbers of older people and decreasing rates of edentulism highlight
      the importance of dental education that focuses on oral health and ageing. Our
      evaluation study was carried out to assess the Indian dental graduate's geriatric
      knowledge, as well as their awareness, of the bio-psychosocial factors that are
      potential barriers to geriatric oral health care. A total of 98 students were
      evaluated during their rotational clinical posting in the fifth year of the
      dental education programme. The results suggest that general attitudes need to be
      changed by the inclusion of geriatric dentistry in the dental curriculum.
      Exposure of students to didactic and clinical setting appears to be a critical
      element towards positive knowledge and attitude of the elderly.

PMID- 20825499
TI  - Immune tolerance induction for a patient with factor IX inhibitors--a case
      report.

PMID- 20825501
TI  - Inter-observer reliability of three different radiographic scores for adult
      haemophilia.
AB  - To evaluate the inter-observer reliability of radiological assessment systems for
      haemophilic arthropathy, three senior orthopaedic surgeons with expertise in
      haemophilia independently evaluated a total of 527 joint radiographs of adult
      haemophilia patients, without any knowledge of the clinical data. This study was
      the largest study to evaluate the reliability of radiological assessment systems.
      As for the results, the Arnold-Hilgartner staging system showed moderate
      reliability (kappa value: kappa = 0.44, P = 0.000), and the De Palma grading
      system and the Pettersson scoring system showed fair reliability (kappa = 0.40, P
      = 0.000) and slight reliability (kappa = 0.12, P = 0.000) respectively. As for
      the reliability of the eight findings in the Pettersson scoring system, three
      findings, which were 'narrowing of joint space' (kappa = 0.70 P = 0.000),
      'irregular subchondral surface' (kappa = 0.58, P = 0.000) and 'erosion of joint
      margins' (kappa = 0.56, P = 0.000), showed substantial or moderate reliability.
      Other findings showed fair or less reliability. The traditional radiological
      assessment systems showed poor inter-observer reliability. Both progressive
      scales showed higher reliability than the additive scale, and the three findings
      in the Pettersson scoring system showed good reliability. These results suggested
      that the progressive scale, including the three reliable radiological findings,
      might be a more reliable radiological assessment system.

PMID- 20825500
TI  - Identifying non-responsive bleeding episodes in patients with haemophilia and
      inhibitors: a consensus definition.
AB  - Assessing response to treatment with bypassing agents presents a substantial
      challenge in the treatment of patients with haemophilia and inhibitors. Rapid and
      accurate identification of bleeding episodes that are non-responsive to bypassing
      therapy with either Factor Eight Inhibitor Bypassing Activity (FEIBA; Baxter AG)
      or recombinant activated factor VII (rFVIIa; NovoSeven(r) , Novo Nordisk A/S) is
      essential to guide treatment decisions and optimize patient outcomes through
      early intervention. Although both bypassing agents are effective, differential
      responses to therapy necessitate multiple therapeutic options. This article
      provides a consensus definition for non-life-threatening joint and muscle bleeds
      that are non-responsive to bypassing agents. An international panel of seven
      physicians met in December 2008 to develop the consensus definition using a
      modified National Institutes of Health Consensus Development Conference method.
      The consequent definition of non-life-threatening bleeding episodes that are non
      responsive to bypassing treatment provides a global picture of the condition of
      the patient during such an event. Identification of non-responsiveness is based
      on various criteria: pain, swelling/tension, mobility, patient perception and
      laboratory parameters. Criteria can be assessed subjectively by the
      patient/parent and/or objectively by the clinician. Although the precise timing
      of each determination should be at the discretion of the physician, bleeds should
      be considered non-responsive if the clinical situation meets the specified
      criteria 24 h from the start of treatment. Although it is not intended to replace
      clinical judgment, this definition can guide the optimal course of treatment for
      patients with haemophilia and inhibitors.

PMID- 20825502
TI  - Comparative study of dual energy X-ray absorptiometry and quantitative
      ultrasonography with the use of biochemical markers of bone turnover in boys with
      haemophilia.
AB  - Our aim was to evaluate bone status in boys with haemophilia using dual energy X
      ray absorptiometry (DXA) and quantitative ultraSonography (QUS), and in addition,
      to compare these two methods with the use of biochemical markers of bone
      turnover. Twenty-six boys with a mean decimal age of 12.08 +/- 4.44 years were
      included in the study which included a DXA scan at lumbar spine and radial, as
      well as tibial QUS. Serum levels of soluble receptor activator of nuclear factor
      kappaB ligand (sRANK-L), osteoprotegerin (OPG) and osteocalcin (OC) were measured
      and joint evaluation was performed using the Hemophilia Joint Health Score
      (HJHS). With regard to the study results, only 2 of 26 patients (7.7%) had bone
      mineral density (BMD) Z-scores < -2, and 4 patients (15.4%) had BMD Z-scores
      between -1 and -2. Only one patient had radial and other two had tibial QUS Z
      scores < -2. No agreement was recorded between QUS and DXA in identifying
      patients at risk for osteoporosis (k = 0.275, P = 0.063). Haemophiliacs had
      significantly higher serum levels of sRANK-L (21.04 +/- 4.78 vs. 18.58 +/- 2.28
      ng mL(-1), P = 0.038) and of OC (5.35 +/- 2.29 vs. 3.09 +/- 0.61 ng mL(-1), P =
      0.002) and significantly decreased levels of OPG (15.78 +/- 2.53 vs. 23.79 +/-
      4.39 pg mL(-1), P < 0.001) compared with controls. QUS Z-scores at tibia
      significantly correlated with HJH Scores (r = -0.450, P = 0.040), whereas lumbar
      BMD Z-scores significantly correlated with body mass index Z-scores (r = 0.500, P
      = 0.009). More studies are warranted to identify the most accurate densitometric
      method for assessing bone status in haemophiliacs.

PMID- 20825503
TI  - Von Willebrand disease caused by compound heterozygosity for p.r854q and p.r760c:
      diagnostic and therapeutic implications.

PMID- 20825504
TI  - Analysis of low frequency bleeding data: the association of joint bleeds
      according to baseline FVIII activity levels.
AB  - Many studies in the field of haemophilia and other coagulation deficiencies
      require analyses of bleeding frequencies. In haemophilia, the association of
      bleeding frequency with factor VIII (FVIII) activity levels is known from
      experience, but significant results are lacking. Bleeding frequencies in
      haemophilia are highly skewed count data, with large proportions of zeros. Both
      the skewness and the high amount of zeros pose a problem for standard (linear)
      modelling techniques. This study investigated the optimal analysing strategy for
      bleeding data by using the association of residual clotting factor level and
      number of joint bleeds in moderate and mild patients treated on demand as
      example. In total, 433 patients with moderate (27%) and mild (73%) haemophilia A
      treated on demand were included in this study. One year of self-reported data on
      joint bleed frequency and baseline clotting factor activity were analysed using
      Poisson, negative binomial, zero-inflated Poisson, and zero-inflated negative
      binomial distributions. Multivariate regression analysis using negative binomial
      distribution provided the optimum data analytical strategy. This model showed 18%
      reduction [Rate ratio (RR) 0.82; 95%confidence interval (CI) 0.77-0.86] of
      bleeding frequency with every IU dL(-1) increase in residual FVIII activity. The
      actual association is expected to be higher because of exclusion (30 out of 463
      patients) of patients on prophylaxis (baseline FVIII levels 0.01-0.06 IU mL(-1)).
      The best way to analyse low frequency bleeding data is using a negative binomial
      distribution.

PMID- 20825505
TI  - Perceived competence in children and adolescents with haemophilia: an explorative
      study.
AB  - With the introduction of prophylaxis, restricting children with haemophilia to
      participate in physical activities was no longer necessary. Subsequently, many
      studies report on improved physical functioning in children and adolescents with
      haemophilia. However, little is known about psychological aspects such as
      perceived competence and impact of disease. Therefore, the aims of this study
      were to explore: (i) perceived competence, (ii) perceived impact of illness, and
      (iii) analyse associations between perceived competence and demographic factors,
      disease-related factors and joint status in young haemophiliacs in the
      Netherlands. Fifty-four children (age 8-12 years) and 72 adolescents (12-18
      years) with haemophilia participated in this cross-sectional, multi-centre,
      explorative study. Measurements included perceived competence (Self Perception
      Profile for Children/Adolescents; range 6-24/5-20), impact of disease (Revised
      Perception Illness Experience; range 1-5), demographic factors, disease-related
      factors, joint status and functional status. Mean (SD) scores for perceived
      competence in the children ranged from 17.3 (+/-4.0) to 19.6 (+/-4.0), and for
      adolescents from 13.3 (+/-2.4) to 15.7 (+/-2.8) points. In general, scores were
      comparable with those of healthy peers, but children with haemophilia had a lower
      global self-worth score and competence in close friendship was lower for
      adolescents when compared with those of healthy peers. Mean (SD) scores for
      impact of disease ranged from 1.2 (+/-0.4) to 2.3 (+/-0.8) in children and from
      1.3 (+/-0.4) to 2.0 (+/-0.8) in adolescents. Severe haemophilia, prophylactic
      medication, high impact of disease and a shorter walking distance showed a weak
      to moderate association with perceived competence. Children and adolescents with
      haemophilia in general have a perceived competence that is nearly comparable with
      that of healthy peers, with the exception of a lower global self-worth in
      children and a lower competence for close friendship in adolescents.
      Haemophiliacs seem to perceive their disease as having relatively low impact on
      their life. Severe disease, prophylactic treatment and low functional status
      seemed to be associated with lower perceived competence.

PMID- 20825506
TI  - Transcription factors BmPOUM2 and BmbetaFTZ-F1 are involved in regulation of the
      expression of the wing cuticle protein gene BmWCP4 in the silkworm, Bombyx mori.
AB  - In Bombyx mori, the wing cuticle protein gene BmWCP4 is expressed specifically in
      the epidermis at the onset and mid-stage of pupation and is responsible for the
      formation of the pupal cuticle during the larval-pupal metamorphosis. The gene
      consists of four exons and three introns and is present as a single copy in the
      genome. Its expression was up-regulated by 20-hydroxyecdysone (20E) and the 20E
      induced expression was suppressed by juvenile hormone (JH) III. The upstream
      regulatory sequence region of the BmWCP4 gene was cloned and the regulatory
      elements responsible for 20E induction were identified. Two cis-regulatory
      elements (CREs) bound by the transcription factors BmPOUM2 and BmbetaFTZ-F1 were
      identified that mediated 20E-regulated expression of this gene. An
      electrophoretic mobility shift assay detected two nuclear proteins isolated from
      the epidermis and the BmN cell line that specifically bound to the POU and
      betaFTZ-F1 CREs, respectively. BmPOUM2 recombinant protein explicitly bound to
      the POU CRE. Developmental and 20E-induced expression of the BmWCP4, BmPOUM2 and
      BmbetaFTZ-F1 genes showed that BmPOUM2 and BmbetaFTZ-F1 were initially expressed,
      followed by BmWCP4. These data suggest that the 20E-induced expression of BmWCP4
      is mediated by the transcription factors BmPOUM2 and BmbetaFTZ-F1 binding to
      their CREs in the regulatory sequence region of the BmWCP4 gene.

PMID- 20825507
TI  - Radiculomegaly of permanent canines: report of endodontic treatment in OFCD
      syndrome.
AB  - AIM: To present a case describing the endodontic treatment of a permanent canine
      with radiculomegaly and to draw the attention of the endodontic community to this
      rare anomaly. SUMMARY: Oculo-facio-cardio-dental (OFCD) syndrome is a rare X
      linked dominant syndrome characterized by canine teeth with extremely large roots
      (radiculomegaly), dental abnormalities, congenital cataracts, dysmorphic facial
      features and congenital heart disease. The diagnosis of this syndrome is
      difficult. Unique and specific symptoms, which can be diagnosed by an endodontist
      or a general dentist, are present in the dental, skeletal, ocular and cardiac
      structures. Worldwide, only 20 cases of this syndrome have been reported to date.
      The patient presented in this study was a 17-years-old girl with a mandibular
      right canine (47.5mm) tooth with two canals. KEY LEARNING POINTS:   *  Clinicians
      should be aware of anatomical variations in cases with OFCD syndrome. *  Root
      canal treatment in such cases is challenging. *  In general, the majority of
      mandibular canines have one root and root canal, but 15% may have two canals, and
      a smaller number may have two distinct roots.

PMID- 20825508
TI  - Treatment and orthodontic movement of a root-fractured maxillary central incisor
      with an immature apex: 10-year follow-up.
AB  - AIM: To report a maxillary central incisor tooth with a horizontal root fracture
      and incomplete root development that healed and was then moved orthodontically
      some years after the traumatic injury. SUMMARY: A 7-year-old girl attended
      following trauma to the maxillary anterior region. Radiologic examination
      revealed a horizontal root fracture in the middle third of the maxillary right
      central incisor tooth that had an immature apex. After early treatment, the
      fractured tooth healed and pulpal health was retained. Recall examination after
      2years revealed complete root development. Orthodontic treatment was performed to
      correct an angle type I malocclusion. Clinical and radiologic controls were
      performed over 10years and confirmed both pulpal and periodontal health. KEY
      LEARNING POINT: *  Orthodontic movements of teeth with previously fractured roots
      might be possible without adverse pulpal effects.

PMID- 20825509
TI  - Updated Japanese Urological Association Guidelines on  prostate-specific antigen
      based screening for prostate  cancer in 2010.
AB  - The exposure rate of screening for prostate cancer using prostate-specific
      antigen (PSA) in Japan is still very low compared with that in the USA or western
      Europe. The mortality rate of prostate cancer will increase in the future and in
      2020 it will be 2.8-fold higher than in 2000. Therefore, there is an urgent need
      to determine the best available countermeasures to decrease the rate of prostate
      cancer death. PSA screening, which can reduce the risk of death as a result of
      prostate cancer, should be offered to all men at risk of developing prostate
      cancer with fact sheets showing updated benefits and drawbacks of screening for
      prostate cancer.

PMID- 20825510
TI  - Retrospective evaluation of clinical outcomes in subjects with split-thickness
      skin graft: comparing V.A.C.(r) therapy and conventional therapy in foot and
      ankle reconstructive surgeries.
AB  - This retrospective study compared the clinical outcomes of negative pressure
      wound therapy with reticulated open cell foam (NPWT/ROCF) as delivered by Vacuum
      Assisted Therapy((r)) (V.A.C.((r)) Therapy, KCI Licensing Inc., San Antonio, TX)
      to non-NPWT/ROCF conventional therapy (CT) in split-thickness skin graft (STSG)
      survival in all patients to determine whether NPWT/ROCF affects the outcome of
      the graft survival, in terms of overall graft take, duration of graft take,
      repeated grafts and complications. The authors conducted a 10-year retrospective
      review of 142 patients admitted to a level I trauma centre and treated with an
      STSG in foot and ankle reconstructive surgeries. Demographic data, wound
      etiology, dressing type used, time to graft take, NPWT/ROCF duration,
      complications and outpatient treatments were analysed. There were significantly
      fewer repeated STSGs required in the NPWT/ROCF group compared to CT [n = 3 (3.5%)
      versus n = 9 (16%); P = 0.006]. In assessing safety, there were fewer
      complications in graft failure (seroma, hematoma and infection) in the NPWT/ROCF
      group as compared to the CT group at 8.9 months (range: 1-12 months). NPWT/ROCF
      is an excellent alternative for securing an STSG and is associated with improved
      graft survival as measured by a reduction in the number of repeated STSGs and
      graft failure complications.

PMID- 20825511
TI  - Association of breathlessness with multiple symptoms in chronic obstructive
      pulmonary disease.
AB  - AIM: This paper is a report of an exploration of relationships between
      demographic and clinical variables and the symptoms of breathlessness,
      depression, anxiety, fatigue, sleeping difficulties and pain for patients with
      chronic obstructive pulmonary disease. BACKGROUND: Research into chronic
      obstructive pulmonary disease has focused on single symptoms and we lack
      knowledge about possible associations between several symptoms. METHODS: A total
      of 154 patients with chronic obstructive pulmonary disease participated in a
      cross-sectional study from June 2006 to December 2007 (response rate 40%). All
      underwent pulmonary lung function tests and completed questionnaires including
      demographic variables, the Brief Pain Inventory, Hospital Anxiety and Depression
      Scale, Lee Fatigue Scale, General Sleep Disturbance Scale and the Respiratory
      Quality of Life Questionnaire. Bivariate correlation and multiple regression
      analyses were performed. RESULTS: Breathlessness was statistically significantly
      positively associated with the other symptoms, after controlling for demographic
      and clinical variables. Younger age was statistically significantly related to
      more breathlessness, anxiety and sleeping difficulties and lower levels of
      education was statistically significantly related to more breathlessness,
      depression and anxiety. In relation to clinical variables, smoking was
      statistically significantly related to more depression, whereas more co-morbidity
      was statistically significantly related to more breathlessness and pain. Poorer
      lung function was statistically significantly related to more breathlessness.
      However, higher lung function was related to more sleeping difficulties.
      CONCLUSION: Breathlessness is associated with symptoms such as depression,
      anxiety, fatigue, sleeping difficulties and pain, suggesting the need for an
      expanded focus on symptoms in chronic obstructive pulmonary disease guidelines,
      health care and research.

PMID- 20825512
TI  - Implementing evidence-based practice: effectiveness of a structured multifaceted
      mentorship programme.
AB  - AIM: This paper is a report of the effectiveness of a structured multifaceted
      mentorship programme designed to implement evidence-based practice in a clinical
      research intensive environment. BACKGROUND: Barriers to implementing evidence
      based practice are well-documented in the literature. Evidence-based practice is
      associated with higher quality care and better patient outcomes than care that is
      steeped in tradition. However, the integration of evidence-based practice
      implementation into daily clinical practice remains inconsistent, and the chasm
      between research and bedside practice remains substantial. METHODS: This quasi
      experimental mixed methods study included three focused discussions with nursing
      leadership and shared governance staff as well as pre- (N = 159) and post
      intervention (N = 99) questionnaires administered between June 2006 and February
      2007. Online questionnaires included measures of organizational readiness,
      evidence-based practice beliefs, evidence-based practice implementation, job
      satisfaction, group cohesion and intent to leave nursing and the current job.
      Results.  Participants in the evidence-based practice mentorship programme had a
      larger increase in perceived organizational culture and readiness for evidence
      based practice and in evidence-based practice belief scores than those who did
      not participate. Qualitative findings suggested that leadership support of a
      culture for evidence-based practice and the dedication of resources for
      sustainability of the initiative needed to be a priority for engaging staff at
      all levels. CONCLUSION: These findings corroborate other studies showing that
      nurses' beliefs about evidence-based practice are significantly correlated with
      evidence-based practice implementation and that having a mentor leads to stronger
      beliefs and greater implementation by nurses as well as greater group cohesion,
      which is a potent predictor of nursing turnover rates.

PMID- 20825513
TI  - Family presence preference when patients are receiving resuscitation in an
      accident and emergency department.
AB  - AIM: This paper is a report of a study to illuminate the experience of family
      members whose relatives survived the resuscitation in an accident and emergency
      department, and their preferences with regard to being present. BACKGROUND:
      Family presence during resuscitation can offer benefits to both patient and
      family members, and large healthcare organizations support and recommend offering
      the option for their presence. However, many staff believe that this is too
      distressing or traumatic for families and that they would interfere with the
      resuscitation process. METHODS: An interpretive phenomenological approach was
      used to collect data in 2007-2008 with 18 family members of patients who survived
      life-sustaining interventions in an accident and emergency department in Hong
      Kong. Audio-recorded interviews were transcribed verbatim for thematic analysis
      and verified with the participants in second interviews. FINDINGS: None of the
      family members was present in resuscitation room during the life-sustaining
      interventions, and five entered the room after the patients' condition was
      stable. The majority indicated a strong preference to be present if given the
      option. Three interrelated themes emerged: (i) emotional connectedness, (ii)
      knowing the patient, and (iii) perceived (in)appropriateness, with 10 subthemes
      representing affective, rational and contextual determinants of family presence
      preferences. The interplay of these determinants and how they contributed to
      strong or weak preference for family presence was analysed. CONCLUSION:
      Variations among the contributing determinants to each family member's preference
      to be present were revealed. Appropriate nursing interventions, policy and
      guidelines should be developed to meet individualized needs during such critical
      and life-threatening moments in accident and emergency departments.

PMID- 20825514
TI  - Center for Epidemiologic Studies Depression Scale for Children: psychometric
      testing of the Chinese version.
AB  - AIM: This paper is a report of psychometric testing of the Chinese version of the
      Center for Epidemiologic Studies Depression Scale for Children. BACKGROUND: The
      availability of a valid and reliable instrument that accurately detects
      depressive symptoms in children is crucial before any psychological intervention
      can be appropriately planned and evaluated. There is no such an instrument for
      Chinese children. METHODS: A test-retest, within-subjects design was used. A
      total of 313 primary school students between the ages of 8 and 12 years were
      invited to participate in the study in 2009. Participants were asked to respond
      to the Chinese version of the Center for Epidemiologic Studies Depression Scale
      for Children, short form of the State Anxiety Scale for Children and Rosenberg's
      Self-Esteem Scale. The internal consistency, content validity and construct
      validity and test-retest reliability of the Chinese version of the Center for
      Epidemiologic Studies Depression Scale for Children were assessed. RESULTS: The
      newly-translated scale demonstrated adequate internal consistency, good content
      validity and appropriate convergent and discriminant validity. Confirmatory
      factor analysis added further evidence of the construct validity of the scale.
      CONCLUSION: Results suggest that the newly-translated scale can be used as a self
      report assessment tool in detecting depressive symptoms of Chinese children aged
      between 8 and 12 years.

PMID- 20825515
TI  - Laparoscopic surgery for endometrial cancer: a phenomenological study.
AB  - AIM: This paper is a report of a study of women's perspectives on the experience
      of laparoscopic surgery for endometrial cancer. BACKGROUND: Laparoscopic surgery
      is increasingly used to treat early endometrial cancer. It is associated with low
      levels of morbidity and is considered safe as cancer surgery, but research on
      quality of life and women's experiences is limited. METHOD: Heideggerian
      hermeneutic phenomenology was used to explore the experiences of 14 women who had
      undergone the procedure in two English cancer centres between February 2008 and
      July 2009. In-depth interviews were taped, transcribed and analysed using
      Colaizzi's framework. FINDINGS: A phenomenological description was produced from
      five identified themes: having cancer, transfer of responsibility to the surgeon,
      information and support, independence, and normality. The experience of
      laparoscopic surgery was overshadowed by the presence of cancer. Fear and lack of
      knowledge played an important role in entrusting the surgeon with the
      responsibility for decision-making. Individual, unmet information needs focused
      on the practicalities of treatment and being in an unfamiliar situation and
      environment. Loss of control and vulnerability were associated with illness and
      surgery, but early postoperative mobility and reduced pain, facilitated rapid
      return to independence and maintained a sense of normality. CONCLUSION:
      Healthcare professionals should deliver care in early endometrial cancer in a way
      that recognizes the significance of the cancer diagnosis, the role of the surgeon
      in decision-making and the need for practical information. Women with endometrial
      cancer should have access to treatments that reduce dependency and maintain
      normality.

PMID- 20825516
TI  - Nurses' risk assessment judgements: a confidence calibration study.
AB  - AIM: This paper is a report of a study of the relationship between nurses'
      clinical experience and calibration of their self-confidence and judgement
      accuracy for critical event risk assessment judgements. BACKGROUND:
      Miscalibration (i.e. under-confidence or over-confidence of confidence levels)
      has an important impact on the quality of nursing care. Despite this, little is
      known about how nurses' subjective confidence is calibrated with the accuracy of
      their judgments. METHODS: A sample of 103 nursing students and 34 experienced
      nurses were exposed to 25 risk assessment vignettes. For each vignette they made
      dichotomous judgements of whether the patient in each scenario was at risk of a
      critical event, and assigned confidence ratings (0-100) to their judgement calls.
      The clinical vignettes and judgement criteria were generated from real patient
      cases. The methodology of confidence calibration was used to calculate
      calibration measures and generate calibration curves. Data were collected between
      March 2007 and January 2008. FINDINGS: Experienced nurses were statistically
      significantly more confident than students but no more accurate. Whilst students
      tended towards under-confidence, experienced nurses were over-confident.
      Experienced nurses were no more calibrated than students. Experienced nurses were
      no better at discriminating between correct and incorrect judgements than
      students. These patterns were exacerbated when nurses and students were extremely
      over-confident or extremely under-confident. CONCLUSION: Nurses were
      systematically biased towards over/under-confidence in their critical event risk
      assessment judgements. In particular, experienced nurses were no better
      calibrated than their student counterparts; with student under-confidence
      countered by experienced nurses' greater susceptibility to over-confidence.

PMID- 20825517
TI  - Characterizing demographic variation and contributions to population growth rate
      in a declining population.
AB  - 1. Understanding how demographic variation translates into variation in
      population growth rate (lambda) is central to understanding population dynamics.
      Such understanding ideally requires knowledge of the mean, variance and
      covariance among all demographic rates, allowing the potential and realized
      contribution of each rate to lambda to be estimated. Such studies require
      integrated monitoring of all demographic rates across multiple years and are
      consequently rare, particularly in declining populations and for species with
      less tractable life histories. 2. We used 12 years of comprehensive demographic
      data from a declining ring ouzel (Turdus torquatus) population to estimate the
      mean, variance and covariance in all major demographic rates and estimate
      potential and realized demographic contributions to lambda. 3. Population size
      decreased from 39 to 13 breeding pairs (-67%) and mean lambda was 0.91 during
      1998-2009. This decrease did not reflect a substantial concurrent decrease in any
      single key demographic rate, but reflected varying combinations of demographic
      rates that consistently produced lambda < 1. 4. Basic prospective elasticity
      analysis indicated that lambda was most sensitive to adult survival, closely
      followed by early season reproductive success and early brood first-year
      survival. In contrast, integrated elasticity analysis, accounting for estimated
      demographic covariance, indicated that lambda was most sensitive to early brood
      first-year survival, closely followed by re-nesting rate, early season
      reproductive success, late-brood first-year survival and adult survival. 5.
      Retrospective decomposition of variance suggested that first-year survival
      contributed most to observed variation in lambda. 6. However, demographic
      comparison with other related species suggested that adult survival, but not
      reproductive success or post-fledging survival, averaged lower than expected
      throughout the 12-year study. 7. These data demonstrate that multiple approaches,
      including comprehensive demographic and comparative analyses and due
      consideration of conflicting answers, may be necessary to accurately diagnose the
      demographic basis of population change.

PMID- 20825518
TI  - Genetic and structural comparison of linoleate isomerases from selected food
      grade bacteria.
AB  - AIMS: To advance the understanding of the molecular mechanisms underlying the
      capacity of bifidobacteria and lactic bacteria to convert linoleic acid (LA) into
      conjugated linoleic acid (CLA) by the linoleate isomerase (LI). METHODS AND
      RESULTS: The potential LI enzymes of selected Lactobacillus, Bifidobacterium and
      Leuconostoc strains were compared at the genetic, amino acid sequence and
      functional levels. Genetic analysis was achieved by insertional mutagenesis and
      hybridization studies using a Lact. reuteri LI probe. Biotransformation studies
      monitored by gas chromatography showed that Bif. breve is a major CLA producer
      after the reference Lact. reuteri strain. The putative Bif. breve LI gene was PCR
      isolated and sequenced. CONCLUSIONS: The putative LI gene identified in this
      study seems essential for bacterial growth. Comparative studies indicate that the
      deduced protein is membrane bound and reveal the presence of several highly
      conserved domains among a wide range of Gram-positive bacteria. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Given the multiple health benefits of CLA, the capability of
      some bacteria to convert LA into CLA is of great relevance. Nevertheless, the
      yields of CLA remain low, and the regulation of the process is far from being
      understood. A deeper knowledge of this capacity by the genetic studies is
      revealing the identity of the LI and will eventually contribute to its control.

PMID- 20825519
TI  - Isolation and characterization of a Pseudomonas sp. strain IITR01 capable of
      degrading alpha-endosulfan and endosulfan sulfate.
AB  - AIM: To isolate bacteria capable of degrading endosulfan (ES) and the more toxic
      ES sulfate and to characterize their metabolites. METHODS AND RESULTS: A
      Pseudomonas sp. strain IITR01 capable of degrading alpha-ES and toxic ES sulfate
      was isolated using technical-ES through enrichment culture techniques. No growth
      and no degradation were observed using beta-ES. Thin-layer chromatography and gas
      chromatography-mass spectrum analysis revealed the disappearance of both alpha-ES
      and ES sulfate and the formation of hydroxylated products ES diol, ether and
      lactone. We show here for the first time the formation of aforementioned
      metabolites in contrast to ES hemisulfate yielded by an Arthrobacter sp.
      Metabolism of alpha-ES and endosulfate was also observed using the crude cell
      extract of IITR01. The molecular mass of protein induced during the degradation
      of alpha-ES and sulfate as substrate was found to be approximately 150 kDa as
      determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE). CONCLUSION: We describe characterization of bacterium capable of degrading
      alpha-ES and ES sulfate but not beta-ES. Genetic investigation suggests that a
      gene nonhomologous to the reported esd may be present in the strain IITR01.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study describes toxic ES degradation
      by a Pseudomonas species that may be utilized for the bioremediation of the
      industrial soils contaminated with ES residues.

PMID- 20825520
TI  - Biological responses of Bacillus stratosphericus to floating electrode-dielectric
      barrier discharge plasma treatment.
AB  - AIMS: Dielectric barrier discharge (DBD) plasma is used for sterilization of
      contaminated inanimate surfaces but seldomly optimized and depends upon the type
      of organisms and the plasma treatment duration, (net energy deposited) this
      efficacy varies. The proposed study was designed to see biological responses of
      one of the robust organism, Bacillus stratosphericus. METHODS AND RESULTS: DBD
      plasma was applied over various durations to B. stratosphericus either surface
      dried or suspension in de-ionized water, and viability, culturability, and viable
      but nonculturability (VBNC) were assayed using standard techniques. Depending
      upon the exposure of B. stratosphericus to DBD plasma resulted in three viability
      states, viable and culturable at low plasma doses and VBNC or disintegrated
      bacteria at higher plasma doses. Although organism's respiration levels at
      relatively low levels, immediately after plasma treatment, over the course of 24
      h respiratory activity was increased c. eight times (and found still
      nonculturable during colony assays). CONCLUSIONS: The loss of culturability is
      hypothesized to be induced as one of the responses to oxidative stress and it
      remains to be unclear if the response is temporary or indefinite. Appropriate
      plasma powers should be used to avoid VBNC-like status. 2,3-Bis-(2-methoxy-4
      nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay is a good
      alternative method to detect VBNC state. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Bacillus stratosphericus has the potential to turn into VBNC upon plasma
      application, and XTT assay can be an alternative method to detect VBNC state.

PMID- 20825521
TI  - Regenerative medicine: then and now--an update of recent history into future
      possibilities.
AB  - The fields of tissue engineering (TE) and regenerative medicine (RegMed) are yet
      to bring about the anticipated therapeutic revolution. After two decades of
      extremely high expectations and often disappointing returns both in the medical
      as well as in the financial arena, this scientific field reflects the sense of a
      new era and suggests the feeling of making a fresh start although many scientists
      are probably seeking reorientation. Much of research was industry driven, so that
      especially in the aftermath of the recent financial meltdown in the last 2 years
      we have witnessed a biotech asset yard sale. Despite any monetary shortcomings,
      from a technological point of view there have been great leaps that are yet to
      find their way to the patient. RegMed is definitely bound to play a major role in
      our life because it embodies one of the primordial dreams of mankind, such as:
      everlasting youth, flying, remote communication and setting foot on the moon. The
      Journal of Cellular and Molecular Medicine has been at the frontier of these
      developments in TE and RegMed from its beginning and reflects recent scientific
      advances in both fields. Therefore this review tries to look at RegMed through
      the keyhole of history which might just be like looking 'back to the future'.

PMID- 20825522
TI  - Dynamic changes in anger, externalizing and internalizing problems: attention and
      regulation.
AB  - BACKGROUND: Low levels of dispositional anger and a good attention span are
      critical to healthy social emotional development, with attention control
      reflecting effective cognitive self-regulation of negative emotions such as
      anger. Using a longitudinal design, we examined attention span as a moderator of
      reciprocal links between changes in anger and changes in externalizing and
      internalizing problems from 4.5 to 11 years of age. METHOD: Participants were
      children from the Study of Early Child Care and Youth Development (SECCYD),
      assessed four times between 4.5 and 11 years. Composite scores for anger and
      attention were computed using indicators from multiple informants. Externalizing
      and internalizing problems were reported by mothers. RESULTS: Latent difference
      score analysis showed reciprocal lagged effects between increased anger and
      elevated levels of externalizing or internalizing problems. Significant
      moderating effects of attention indicated more persistent effects of anger on
      externalizing problems in the poor attention group. Although the poor and the
      good attention groups did not differ regarding the effects of anger on
      internalizing problems, significant moderating effects of attention indicated
      stronger and more persistent reciprocal effects of internalizing problems on
      anger in the poor attention group. CONCLUSIONS: Attention control mechanisms are
      involved in self-regulation of anger and its connections with changes in
      behavioral and emotional problems. Strong attention regulation may serve to
      protect children with higher levels of dispositional anger from developing
      behavioral and emotional problems in middle childhood.

PMID- 20825523
TI  - Effect of atorvastatin on chronic periodontitis: a randomized pilot study.
AB  - AIM: We studied the effect of atorvastatin (ATV) treatment on bone loss
      prevention in subjects with chronic periodontitis. MATERIAL AND METHODS: In this
      controlled double-blind study, 38 subjects with chronic periodontitis were
      randomized into two groups, paired by age to receive ATV (20 mg) or placebo daily
      for 3 months. Periodontal mechanical treatment was carried out in both groups at
      baseline. Clinical and radiographic parameters and bone turnover markers were
      assessed at baseline and at 3 months. RESULTS: Periodontal disease conditions
      improved in both groups. After comparing the figures of change, significant
      improvements were observed in cholesterol levels (Delta=-58.5 +/- 37.6
      versusDelta=5.4 +/- 41.2 mg/dl, p<0.0002), low-density lipoprotein levels (Delta=
      48.1 +/- 31.7 versusDelta=1.9 +/- 42.8 mg/dl, p<0.002), dental mobility (Delta=
      0.17 +/- 0.11 versusDelta=-0.06 +/- 0.11%, p<0.04), and the distance from the
      crestal alveolar bone to the cemento-enamel junction (Delta=-0.75 +/- 0.7
      versusDelta=0.09 +/- 0.4 mm, p<0.0006) in the ATV group. CONCLUSIONS: The results
      suggest that ATV might have beneficial effects on bone alveolar loss and tooth
      mobility in subjects with periodontal disease.

PMID- 20825524
TI  - Colourful stripes send mixed messages to safe and risky partners in a diffuse
      cleaning mutualism.
AB  - The steps by which neutral, random and/or negative biological interactions evolve
      into mutualistic ones remain poorly understood. Here, we study Elacatinus gobies
      and the 'client' fishes they clean. Colourful stripes are common to mutualist
      cleaners and noncleaning sister species. Blue stripes are unique to cleaners and
      are more conspicuous to predators than are basal yellow or green stripes. In
      turn, we focused on the role of colour as a potentially specialized signal. We
      show that cleaners may possess a chemical defence and demonstrate that stripes
      are sufficient to elicit client posing behaviour and to deter attack,
      corroborating the putative role of chemistry. Analysis of previously published
      records shows that yellow cleaners interact with predatory clients less often
      compared to green and blue cleaners. Our results highlight evolution from
      predator resistance to advertising with conspicuous signals. Similar
      trajectories, via recognizable signals to risky partners, may be common in other
      diffuse mutualisms.

PMID- 20825525
TI  - Mutualism variation in the nodulation response to nitrate.
AB  - The evolution of mutualisms under novel selective pressures will play a key role
      in ecosystem responses to environmental change. Because fixed nitrogen is traded
      in plant-rhizobium mutualisms, increasing N availability in the soil is predicted
      to alter coevolution of these interactions. Legumes typically decrease the number
      of associations (nodules) with rhizobia in response to nitrate, but the
      evolutionary dynamics of this response remain unknown. We grew plant and
      rhizobium genotype combinations in three N environments to assess the
      coevolutionary potential of the nodule nitrate response in natural communities of
      plants and rhizobia. We found evidence for coevolutionary genetic variation for
      nodulation in response to nitrate (G * G * E interaction), suggesting that the
      mutualism response to N deposition will depend on the combination of partner
      genotypes. Thus, the nitrate response is not a fixed mechanism in plant-rhizobium
      symbioses, but instead is potentially subject to natural selection and dynamic
      coevolution.

PMID- 20825527
TI  - Differential niche modification by males and females of a dioecious herb:
      extending the Jack Sprat effect.
AB  - Males and females of dioecious plants often differ in morphological,
      physiological and life-history traits, probably as a result of their different
      requirements for reproduction. We found that the growth and reproductive effort
      of individuals of the dioecious herb Mercurialis annua depended on whether males
      or females had been growing in the soil previously. This suggests that males and
      females of M. annua differentially modify the soil in which they are growing. Our
      study indicates that sexual dimorphism in dioecious plants can give rise to
      increased environmental heterogeneity as a consequence of sex-specific niche
      modification.

PMID- 20825529
TI  - 10 years quality assurance of the dermatologist's procedure. ABD review board
      part II: 2003-2009.
AB  - BACKGROUND: The dermatologist's procedure ("procedure for early detection of
      occupational skin diseases") enables dermatologists to conduct the relevant
      diagnostics at the expenses of the statutory employers' liability insurance funds
      (UVT) if there is a possibility of a work-related skin disorder in an employee.
      Acceptance of this most relevant tool for secondary prevention in occupational
      dermatology in Germany is high and most dermatologists make careful use of this
      unparalleled privilege. However, there have been occasional complaints by the
      UVT, concerning overly extensive diagnostics. Consequently, the Task Force on
      Occupational and Environmental Dermatology (ABD) of the German Society of
      Dermatology set up a review board in May 1999. RESULTS: Dermatologists' reports
      in question were submitted by the UVT to the review board and reviewed separately
      by two experienced occupational dermatologists both in the 1(st) period (1999
      2003) and now in the second period (June 2003 - November 2009). The criticism of
      the reviewers was mostly directed towards the number of tests and an insufficient
      documentation in the dermatologist's report. There were 69 dermatologists'
      reports submitted to the review board (as compared to 155 in the 1(st) period).
      CONCLUSIONS: The decreased number of dermatologists' reports submitted could be a
      result of the review process itself. Other factors may include the optimization
      of the dermatologist's report with a better reimbursement as well as the recent
      publication of guidelines and continuous education in occupational dermatology
      with certification of more than 700 dermatologists. These measures of quality
      assurance are aimed to further optimize the dermatologist's procedure and to
      allow for improved and more rapid care for patients with occupational dermatoses
      by dermatologists.

PMID- 20825530
TI  - Development and validation of a photonumeric grading scale for assessing lip
      volume and thickness.
AB  - BACKGROUND: Currently, there is the need of a validated grading scale for
      assessing lip volume/thickness. OBJECTIVE:   The aim of this study was to assist
      clinicians in managing individuals seeking lip rejuvenation and to provide an
      objective method for evaluating the efficacy and longevity of such treatments.
      METHODS: Using accepted criteria for the development of dermatological grading
      scales, we have developed and validated a photographic grading scale for
      assessing lip volume and thickness based on digital parallel-polarized light
      imaging. RESULTS: The photographic grading scale was shown to be a valid and
      reliable instrument for assessing lip volume and thickness, with good inter- and
      intra-grader consistency. The validity of the scale was demonstrated by its
      correlation with clinical evaluation and 3-dimensional measurements. CONCLUSIONS:
      This validated lip-volume/thickness grading scale should prove helpful in
      clinical trial settings to standardize clinical evaluations and to quantify
      results and measure the longevity of dermal fillers and other procedures for lip
      rejuvenation.

PMID- 20825532
TI  - The spectrum of paediatric dermatoses in a university hospital in Cairo, Egypt.
AB  - BACKGROUND: Epidemiological data on paediatric dermatoses in Egypt are scanty.
      OBJECTIVE: To study the spectrum of paediatric dermatoses in Cairo. METHODS: The
      medical records of children attending the dermatology outpatient clinics of Ain
      Shams University hospital for the year 2001 were retrieved. Data of 3049 patients
      were included. Demographic data (age and gender) and diagnoses were extracted,
      coded and analysed. RESULTS: Patients' attendance peaked in summer (42.57%) and
      revealed female predominance (1.3:1). Infections constituted most of dermatoses
      (52.87%) and impetigo was most common (12.04%). Hypersensitivity came after
      (18.6%), and contact dermatitis prevailed (6.03%). Females predominated in most
      dermatoses. Bacterial infections were the most common in both genders. Age
      distribution revealed prevalence of bacterial infections in infants and preschool
      children, parasitic infections in school children and sebaceous gland disorders
      in adolescents. Parasitic infections prevailed in winter and spring, whereas
      bacterial infections prevailed in summer and autumn. Most dermatoses peaked in
      summer except urticaria and chicken pox that peaked in spring. CONCLUSION:
      Infections outnumbered other paediatric dermatoses parallel to the situation in
      developing communities. Such diseases are potentially controllable and therefore
      strategies that target infections may represent a key to an efficient child
      health care programme.

PMID- 20825533
TI  - Association of doctor specialty with diabetic patient risk of hospitalization due
      to diabetic ketoacidosis: a national population-based study in Taiwan.
AB  - OBJECTIVES: Diabetic ketoacidosis (DKA) is a life-threatening complication of
      diabetes mellitus, and its risks can be largely reduced by adequate and high
      quality ambulatory diabetic care. The aim of this study is to assess the risk and
      frequency of developing DKA in relation to the specialty of doctors who provide
      diabetes cares. METHODS: In searching for possible episodes of hospitalization
      due to DKA (ICD-9-CM: 250.1), we used a prospective cohort design in which
      500,867 diabetic patients identified in the 1997 National Health Insurance (NHI)
      ambulatory care data set of Taiwan were linked to the 1997-2006 NHI inpatient
      claims data. The study subjects were categorized into four groups according to
      doctor specialty. A logistic regression model was used to assess the risk and
      frequency of DKA admission in relation to doctor's specialty. RESULTS: Compared
      with the patients routinely cared by endocrinologists, those not consistently
      cared by endocrinologists had significantly increased odds ratios (ORs) of DKA
      admission, ranging between 1.51 and 2.12. Moreover, the adjusted OR of the higher
      DKA admission frequency (>= 0.133 times/person-year) for the patients not
      regularly cared by endocrinologists was also significantly increased, between
      4.45 and 6.93. CONCLUSIONS: Doctor specialty significantly influenced the risk
      and frequency of DKA admission in diabetes patients in Taiwan. Local health care
      administrators and policy makers should therefore consider promoting the quality
      of diabetes care provided by non-endocrinologists.

PMID- 20825534
TI  - Enablement in health care context: a concept analysis.
AB  - RATIONALE, AIMS AND OBJECTIVES: The enablement process is defined as a
      professional intervention aiming to recognize, support and emphasize the
      patient's capacity to have control over her or his health and life. The purpose
      of this article was to study the enablement concept through a concept analysis in
      the health care context to identify: (1) its attributes and (2) its antecedents
      and consequents. METHOD: A concept analysis was performed according to the method
      of Rodgers. The literature was reviewed from 1980 to June 2008, using search
      strategies adapted to the databases Cinahl, Medline, Embase, PsycInfo and Social
      Works Abstract, and hand searching. All articles contributing to a deeper
      understanding of the concept were included. The analysis was carried out
      according to a thematic analysis procedure, as described by Miles & Huberman.
      RESULTS: The search identified 1305 citations. After in-depth assessment of 148
      potentially eligible citations, 61 articles were included in the review. Five
      articles were added with hand searching. Sixty-seven per cent of these articles
      were related to nursing. The attributes of the enablement concept included:
      contribution to the therapeutic relationship; consideration of the person as a
      whole; facilitation of learning; valorization of the person's strengths;
      implication and support to decision making; and broadening of the possibilities.
      CONCLUSION: These attributes could be used as a basis for other studies on
      enablement. Conceptual and empirical work is still needed to better position this
      concept among others such as patient-centred care, shared decision making and
      patient's participation.

PMID- 20825535
TI  - Dose-response relationship between physiotherapy resource provision with function
      and balance improvements in patients following stroke: a multi-centre
      observational study.
AB  - RATIONALE, AIMS AND OBJECTIVES: Inpatient rehabilitation of patients following
      stroke can be resource intensive, with optimal models of service delivery
      unclear. This study investigates the dose-response curves between physiotherapy
      service delivery variables and balance and function clinical outcomes. METHOD:
      This was a multi-centre (15 sites), prospective, cohort study involving patients
      (n = 288) admitted for rehabilitation following stroke conducted across two
      states in Australia. Physiotherapy department resource provision variables were
      collected and examined for association with change in patient function and
      balance outcomes (Functional Independence Measure, step test, functional reach
      test) measured at admission and discharge from inpatient care. RESULTS: A greater
      amount of log-transformed physiotherapy department resource provision was
      associated with greater improvement in the functional independence measure
      [Regression coefficient (95% CI): 4.05 (1.15, 6.95)] and functional reach test
      [46.43 (17.03, 75.84)], while physiotherapist time provided to patients was
      associated with greater improvement for the step test [0.15 (0.03, 0.28)], and
      functional reach [0.35 (0.19, 0.52)]. CONCLUSION: Receiving a higher rate of
      physiotherapist input is an important factor in attaining a greater amount of
      recovery in function and balance outcomes; however, the improvement by patients
      who received the greatest amount of input was highly variable.

PMID- 20825536
TI  - The accuracy of primary care teams in diagnosing disorders of the shoulder.
AB  - OBJECTIVE: The aim of this retrospective, observational study was to determine
      the accuracy of diagnoses given by a multitude of primary care services to
      patients referred to an orthopaedic upper limb surgeon with a focus towards
      shoulder pathology. METHODS: Records of all patients referred to a single upper
      limb surgeon over a 1-year period were reviewed. The diagnosis in the primary
      care setting was compared with the initial working diagnosis in the specialist
      clinic and against the final diagnosis following specialist
      investigation/intervention. RESULTS: 114 eligible patients were identified.
      General practitioners referred 35% of patients, musculoskeletal triage services
      referred 63% of patients and independent physiotherapists referred 2% of
      patients. It was found that 37% of patients were not given a diagnosis by the
      primary care team. When a diagnosis was given, accuracy was 50% (kappa = 0.28)
      when correlated against that given by an orthopaedic upper limb surgeon.
      CONCLUSIONS: Our findings suggest that knowledge of shoulder conditions is
      limited amongst primary care practitioners. There does not appear to be any
      difference in accuracy between general practitioners and musculoskeletal triage
      services.

PMID- 20825537
TI  - Understanding culture and culture management in the English NHS: a comparison of
      professional and patient perspectives.
AB  - RATIONALE AND OBJECTIVES: The growing interest in patient-focused health care in
      the National Health System (NHS), especially in the wake of high-profile failures
      in clinical practice, has underlined the need to involve patients in the design
      and evaluation of organizational change management programmes at the local level.
      This includes an evaluation of the relevance of culture and how culture might be
      assessed and managed in the delivery of high-quality and safe care. The purpose
      of this study is to compare and contrast the perspectives of health care
      professionals and patient representatives on purposeful attempts to manage
      culture change in the English NHS. METHODS: We used the mixed approach, but with
      more quantitative than qualitative data. A postal questionnaire survey of
      clinical governance leads and patient representatives from 276 NHS trusts was
      followed up with a focus group discussion of eight of the survey participants and
      semi-structured interviews with 18, including health care professionals and
      patient representatives from various organizations. We used spss to analyse the
      survey data and Atlas.ti to analyse the qualitative data. RESULTS AND
      CONCLUSIONS: Both clinical governance leads and patient representatives
      considered culture management and change to be integral to quality and safety
      improvement efforts. However, clinical governance leads were more positive than
      patient representatives about anticipated results from ongoing efforts to manage
      culture change at the local level. Further, in spite of general agreement on
      various attributes for culture assessment efforts, there was a striking
      difference in the level of importance respondents attached to blame free (more
      important to clinical governance managers) and customization (more important to
      patient representatives).

PMID- 20825538
TI  - A retrospective study of drug-related problems in Australian aged care homes:
      medication reviews involving pharmacists and general practitioners.
AB  - BACKGROUND: Drug-related problems (DRPs) in Australian aged care homes have been
      studied previously. However, little is known about the acceptance and
      implementation of pharmacists' recommendations by general practitioners (GPs) to
      resolve DRPs. OBJECTIVES: The primary objective of this study was to investigate
      the number and nature of DRPs identified by accredited clinical pharmacists. The
      secondary objective was to study the GP acceptance and implementation of
      pharmacist recommendations to resolve DRPs. METHODS: This was a retrospective
      study of 500 randomly selected, de-identified medication reviews performed by 10
      accredited clinical pharmacists over 6 months across 62 aged care homes. The DRPs
      identified by pharmacists were subsequently classified by the drugs involved,
      types of problem (indication, effectiveness and safety) and medical diagnoses of
      the patient. GP written feedback on the medication review reports determined
      implementation of pharmacists' recommendations to resolve the DRPs. RESULTS: A
      total of 1433 DRPs were identified in 480 of the 500 residents. Potential DRPs
      were frequently classified as risk of adverse drug reactions, need for additional
      monitoring and inappropriate choice of a drug. Alimentary, cardiovascular,
      central nervous system and respiratory drugs were most frequently implicated,
      accounting for more than 75% of the DRPs. GPs' acceptance and implementation of
      pharmacists recommendations were 72.5% (95% CI; 70.2, 74.8) and 58.1% (95% CI;
      55.5, 60.6), respectively. CONCLUSIONS: Over 96% of the residents had potential
      DRPs identified by pharmacists. GP acceptance of pharmacists' recommendations was
      independent of the drug category, but not independent of the disease category.

PMID- 20825539
TI  - Metabolic syndrome and its components are underdiagnosed in cardiology clinics.
AB  - BACKGROUND: Although metabolic syndrome (MetS) is an important clinical
      condition, evidence is scarce on how often doctors successfully diagnose this
      syndrome. AIMS: To assess the extent of doctors' diagnosis of MetS and its
      components in cardiology outpatient setting and whether such diagnosis affects
      the way patients are counselled on lifestyle modification. METHODS: This is a
      multicentre cross-sectional study on randomly selected clinical notes at
      ambulatory cardiology clinics in three academic centres in the USA. We abstracted
      data on cardiovascular risk factors, and examined whether doctors documented a
      diagnosis of MetS and its components. RESULTS: Of 511 participants who satisfied
      our inclusion criteria, the MetS was present in 246 participants (48%). The
      proportions with which a doctor correctly documented diagnoses were: MetS 9.3%
      (23/246), obesity 60% (119/197), elevated blood pressure 74% (305/412), elevated
      fasting glucose 17% (49/291), reduced high density lipoprotein cholesterol 10%
      (18/190) and elevated triglycerides 20% (32/164). This pattern of diagnoses, less
      frequent with dyslipidaemia and elevated fasting glucose compared with the rest,
      was persistently observed regardless of sex, age, and presence or absence of
      MetS. Those diagnosed were more likely to receive a recommendation of weight loss
      or increase in physical activity than those undiagnosed: 91% (21/23) versus 37%
      (82/223) for weight loss, and 83% (19/23) versus 26% (58/223) for increase in
      physical activity (P < 0.001 for both). CONCLUSIONS: Our data indicate that MetS
      and its components are commonly underdiagnosed in cardiology outpatient setting.
      Better diagnosis may lead to better counselling on lifestyle changes and
      improvement in the quality of care.

PMID- 20825540
TI  - Acclimation of thermal physiology in natural populations of Drosophila
      melanogaster : a test of an optimality model.
AB  - Many organisms modify their physiological functions by acclimating to changes in
      their environment. Recent studies of thermal physiology have been influenced by
      verbal models that fail to consider the selective advantage of acclimation and
      thus make no predictions about variation in acclimation capacity. We used a
      quantitative model of optimal plasticity to generate predictions about the
      capacity of Drosophila melanogaster to acclimate to developmental temperature.
      This model predicts that the ability to acclimate thermal sensitivity should
      evolve when temperature varies greatly among generations. Based on the model, we
      expected that flies from the highly seasonal environment of New Jersey would
      acclimate thermal sensitivity more than would flies from the less seasonal
      environment of Florida. When raised at constant and fluctuating temperatures,
      flies from these populations failed to adjust their thermal optima in the way
      predicted by the model, suggesting that current assumptions about functional and
      genetic constraints should be reconsidered.

PMID- 20825541
TI  - Effects of inbreeding on aversive learning in Drosophila.
AB  - Inbreeding adversely affects life history traits as well as various other fitness
      related traits, but its effect on cognitive traits remains largely unexplored,
      despite their importance to fitness of many animals under natural conditions. We
      studied the effects of inbreeding on aversive learning (avoidance of an odour
      previously associated with mechanical shock) in multiple inbred lines of
      Drosophila melanogaster derived from a natural population through up to 12
      generations of sib mating. Whereas the strongly inbred lines after 12 generations
      of inbreeding (0.75<F<0.93) consistently showed reduced egg-to-adult viability
      (on average by 28%), the reduction in learning performance varied among assays
      (average=18% reduction), being most pronounced for intermediate conditioning
      intensity. Furthermore, moderately inbred lines (F=0.38) showed no detectable
      decline in learning performance, but still had reduced egg-to-adult viability,
      which indicates that overall inbreeding effects on learning are mild. Learning
      performance varied among strongly inbred lines, indicating the presence of
      segregating variance for learning in the base population. However, the learning
      performance of some inbred lines matched that of outbred flies, supporting the
      dominance rather than the overdominance model of inbreeding depression for this
      trait. Across the inbred lines, learning performance was positively correlated
      with the egg-to-adult viability. This positive genetic correlation contradicts a
      trade-off observed in previous selection experiments and suggests that much of
      the genetic variation for learning is owing to pleiotropic effects of genes
      affecting functions related to survival. These results suggest that genetic
      variation that affects learning specifically (rather than pleiotropically through
      general physiological condition) is either low or mostly due to alleles with
      additive (semi-dominant) effects.

PMID- 20825542
TI  - Genetic load, inbreeding depression and heterosis in an age-structured
      metapopulation.
AB  - In a metapopulation, the process of recurrent local extinction and recolonization
      gives rise to an age structure among demes. Recently established demes will tend
      to differ from older demes in terms of the levels of genetic diversity found
      within them and the way this diversity is distributed among demes in the same and
      different ages. The effects of population turnover on average levels of genetic
      diversity among demes in a metapopulation have been the focus of much attention,
      both for neutral and nonneutral loci, but much less is known about the
      distribution of nonneutral genetic diversity among demes of different ages. In
      this paper, we used computer simulations to study the distribution of genetic
      load, inbreeding depression and heterosis in an age-structured metapopulation. We
      found that, for mildly deleterious mutations, within-deme inbreeding depression
      increased, whereas heterosis and genetic load decreased with deme age following
      severe colonization bottlenecks. In contrast, recessive lethal alleles tended to
      be purged during colonization, with older populations showing higher genetic load
      and higher within-deme inbreeding depression. Heterosis caused by recessive
      lethal alleles and resulting from gene flow among different demes tended to be
      greatest for young demes, because the mutations responsible tended to be purged
      in the first few generations after colonization, but its effects increased again
      as populations grow older as a result of immigration. Our results point to a need
      for estimates of genetic diversity, genetic load, within-deme inbreeding
      depression and heterosis in demes of different age classes separately.

PMID- 20825547
TI  - The lifetime costs of increased male reproductive effort: courtship, copulation
      and the Coolidge effect.
AB  - The reproductive effort that a male directs to a familiar female declines over
      time, suggesting decreasing marginal returns. But is this diminishing returns a
      function of increasing reproductive costs or decreasing benefits of sustained
      effort? Here, we use the restoration of male reproductive effort with unfamiliar
      females to differentiate the role of diminishing returns and lifetime costs of
      increased reproductive effort of male guppies. We kept males with familiar or
      unfamiliar females throughout their lives and manipulated their ability to either
      court or mate with females. We found that increased male reproductive effort with
      novel mates lead to an immediate trade-off in the form of reduced foraging
      effort. Further, males able to mate with a series of unfamiliar females had lower
      lifetime growth, indicating the primary cost of male reproductive effort in
      guppies arises from copulation rather than courtship. The lifetime growth trade
      offs were significant only when males mated with unfamiliar mates, suggesting
      that male reproductive effort with familiar females declines before it is
      restricted by physical exhaustion. These findings provide some of the first
      evidence of longitudinal costs of increased male reproductive effort in a
      vertebrate.

PMID- 20825548
TI  - Duplicate retention in signalling proteins and constraints from network dynamics.
AB  - Duplications are a major driving force behind evolution. Most duplicates are
      believed to fix through genetic drift, but it is not clear whether this process
      affects all duplications equally or whether there are certain gene families that
      are expected to show neutral expansions under certain circumstances. Here, we
      analyse the neutrality of duplications in different functional classes of
      signalling proteins based on their effects on response dynamics. We find that
      duplications involving intermediary proteins in a signalling network are neutral
      more often than those involving receptors. Although the fraction of neutral
      duplications in all functional classes increase with decreasing population size
      and selective pressure on dynamics, this effect is most pronounced for receptors,
      indicating a possible expansion of receptors in species with small population
      size. In line with such an expectation, we found a statistically significant
      increase in the number of receptors as a fraction of genome size in eukaryotes
      compared with prokaryotes. Although not confirmative, these results indicate that
      neutral processes can be a significant factor in shaping signalling networks and
      affect proteins from different functional classes differently.

PMID- 20825549
TI  - Enantiomorphs differ in shape in opposite directions between populations.
AB  - Development is left-right reversed between dextral and sinistral morphs of
      snails. In sympatry, they share the same gene pool, including polygenes for shell
      shape. Nevertheless, their shell shapes are not the mirror images of each other.
      This triggered a debate between hypotheses that argue either for a developmental
      constraint or for zygotic pleiotropic effects of the polarity gene. We found that
      dextrals can be wider or narrower than sinistrals depending on the population,
      contrary to the prediction of invariable deviation under a developmental
      constraint. If the pleiotropy is solely responsible instead, the mean shape of
      each morph should change, depending on the frequency of polarity genotype. Our
      simulations of this mean shape change under zygotic pleiotropy, however, show
      that the direction of interchiral difference remains the same regardless of
      genotype frequency. Our results suggest the presence of genetic variation among
      populations that changes the maternal or zygotic pleiotropic effect of the
      polarity gene.

PMID- 20825550
TI  - Higher parasite resistance in Daphnia populations with recent epidemics.
AB  - Natural populations often show genetic variation in parasite resistance, forming
      the basis for evolutionary response to selection imposed by parasitism. We
      investigated whether previous epidemics selected for higher resistance to novel
      parasite isolates in a Daphnia galeata-microparasite system by comparing
      susceptibility of host clones from populations with varying epidemic history. We
      manipulated resource availability to evaluate whether diet influences Daphnia
      susceptibility as epidemics are common in nutrient-rich lakes. Exposing clones
      from 10 lakes under two food treatments to an allopatric protozoan parasite, we
      found that Daphnia originating from lakes (mainly nutrient rich) with previous
      epidemics better resist infection. Despite this result, there was a tendency of
      higher susceptibility in the low food treatment, suggesting that higher
      resistance of clones from populations with epidemic background is not directly
      caused by lake nutrient level. Rather, our results imply that host populations
      respond to parasite-mediated selection by evolving higher parasite resistance.

PMID- 20825551
TI  - Cumulative cultural dynamics and the coevolution of cultural innovation and
      transmission: an ESS model for panmictic and structured populations.
AB  - When individuals in a population can acquire traits through learning, each
      individual may express a certain number of distinct cultural traits. These traits
      may have been either invented by the individual himself or acquired from others
      in the population. Here, we develop a game theoretic model for the accumulation
      of cultural traits through individual and social learning. We explore how the
      rates of innovation, decay, and transmission of cultural traits affect the
      evolutionary stable (ES) levels of individual and social learning and the number
      of cultural traits expressed by an individual when cultural dynamics are at a
      steady-state. We explore the evolution of these phenotypes in both panmictic and
      structured population settings. Our results suggest that in panmictic
      populations, the ES level of learning and number of traits tend to be independent
      of the social transmission rate of cultural traits and is mainly affected by the
      innovation and decay rates. By contrast, in structured populations, where
      interactions occur between relatives, the ES level of learning and the number of
      traits per individual can be increased (relative to the panmictic case) and may
      then markedly depend on the transmission rate of cultural traits. This suggests
      that kin selection may be one additional solution to Rogers's paradox of
      nonadaptive culture.

PMID- 20825552
TI  - The P15 - a multinational assessment battery for collecting data on health
      indicators relevant to adults with intellectual disabilities.
AB  - BACKGROUND: Health disparities between adults with intellectual disabilities (ID)
      and the general population have been well documented but, to date, no dedicated
      assessment battery for measuring health disparity has been available. This paper
      reports on the development and testing of a multinational assessment battery for
      collecting data on a range of health indicators relevant to adults with ID.
      METHODS: An assessment battery (the P15) was developed following piloting, and
      administered to samples of adults with ID, in 14 EU countries. Samples were
      neither random, nor representative of the countries from which they were drawn.
      However, within the local health administration areas selected in each country,
      efforts were made to ensure samples were broadly representative of the typical
      living circumstances, ages and ability levels of the administrative population of
      adults with ID. The total sample comprised 1269 adults with ID, of whom 49% were
      female. The mean age was 41 years (range 19 to 90). RESULTS: Overall,
      feasibility, internal consistency and face validity of the P15 was acceptable.
      CONCLUSIONS: With some refinement the P15 could be useful for collecting data on
      health indicators known to be particularly important for adults with ID. It is
      useable in a range of countries and has the potential to highlight health
      inequity for adults with ID at a national or local level. Larger scale
      epidemiological studies are needed to exploit the potential of the P15 to address
      health inequity in this group.

PMID- 20825553
TI  - Analysis of N- and O-linked protein glycosylation in children with Prader-Willi
      syndrome.
AB  - BACKGROUND: Current genotype-phenotype correlations in Prader-Willi syndrome
      (PWS) are struggling to give an explanation of the diversity in phenotype and
      there is a need to move towards a molecular understanding of PWS. A range of
      functions related to glycoproteins are involved in the pathophysiology of PWS and
      it may be that abnormal glycosylation is contributing to the biological
      phenotype. The objective of this study was to investigate the state of N- and O
      linked glycosylation in children with Prader-Willi syndrome. METHODS: Twenty
      three children with PWS and 20 non-PWS controls were included in the study.
      Protein N-linked glycosylation was assessed by analysing serum transferrin
      through mass spectrometry and protein O-linked through isoelectric focusing (IEF)
      of serum apolipoprotein C-III (apoC-III), confirmed by mass spectrometry.
      RESULTS: The results of this analysis indicated that the N-linked glycosylation
      pathway in PWS is normal. A subgroup of PWS individuals was found to have a
      hyposialylated pattern of apoC-III isoforms. This was independent of the
      underlying genetic mechanism and is the first report of an apoC-III IEF
      abnormality in PWS. CONCLUSIONS: This is the first report of apoC-III
      hyposialylation in PWS. As this field is in its infancy, additional study is
      required before these findings may be used in clinical settings.

PMID- 20825554
TI  - Protein C and/or protein S deficiency and occurrence of stent thrombosis: a
      hitherto unrecognized association.
AB  - OBJECTIVE: To study the prevalence of protein C and/or protein S deficiency in
      patients of stent thrombosis and correlate its association with the event, if
      any. BACKGROUND: Stent thrombosis is the Achilles heel of percutaneous coronary
      intervention (PCI) and has been associated with so many predisposing factors that
      if one analyzes all patients undergoing PCI, one or more such factors would be
      present in almost every patient; however, its incidence remains no more than 1
      2%. We hypothesized a preexisting prothrombotic state, or tendency, in a small
      proportion of patients that possibly plays a key role in its occurrence. METHODS:
      We analyzed the prothrombotic tendency of individual patients by studying protein
      C and protein S levels. Thirteen patients presenting with stent thrombosis and 24
      age- and sex-matched controls were studied. RESULTS: Protein S was found to be
      deficient in 11 of 13 patients (84.6%) of stent thrombosis and in only 4 of 24
      patients (16.7%) in matched controls (P < 0.001), while protein C was found
      deficient in 2 of 12 patients (16.7%) of stent thrombosis, and 1 of 24 patients
      (4.2%) in matched controls (P = 0.25) and either protein C or protein S was
      deficient in 11 of 13 (84.6%) of stent thrombosis and 5 of 24 (20.8%) controls (P
      = <0.001). Low protein S levels were strongly associated with stent thrombosis
      (odds ratio 3.04, 95% confidence interval 1.34-4.7) with sensitivity 0.73 and
      specificity of 0.91. CONCLUSIONS: Protein S deficiency is strongly correlated to
      the occurrence of stent thrombosis, a fact that has hitherto not been recognized
      and needs further evaluation.

PMID- 20825555
TI  - Porphorymonas gingivalis induces intracellular adhesion molecule-1 expression in
      endothelial cells through the nuclear factor-kappaB pathway, but not through the
      p38 MAPK pathway.
AB  - BACKGROUND AND OBJECTIVE: Porphyromonas gingivalis is a major pathogen in the
      development and progression of periodontal disease. The aim of this study was to
      investigate whether endothelial intracellular adhesion molecule-1 (ICAM-1), an
      inflammation biomarker for periodontitis, could be modified by infection with
      either of two strains of P. gingivalis with different virulence capacities:
      avirulent ATCC 33277 and virulent W83. MATERIAL AND METHODS: We examined the
      expression of ICAM-1, IkappaBalpha, phospho-p38 MAPK and nuclear factor-kappaB
      (NF-kappaB) p65 in an umbilical vein endothelial cell line (ECV-304) treated with
      ATCC 33277 and W83, with or without the NF-kappaB antagonist MG132 and/or a
      specific p38 inhibitor (SB203580), by real-time PCR, western blotting and
      immunofluorescence. RESULTS: Both strains could induce ICAM-1 expression;
      additionally W83 was able to increase ICAM-1 expression more significantly than
      ATCC 33277. In P. gingivalis-infected endothelial cells, both p38 MAPK and NF
      kappaB signaling pathways were triggered by a rapid increase of p38 MAPK
      phosphorylation and a more delayed degradation of IkappaBalpha, followed by the
      nuclear translocation of NF-kappaB. It was found that ICAM-1 production in
      endothelial cells was abrogated by inhibition of the NF-kappaB pathway, but not
      by inhibition of the p38 MAPK pathway, using the inhibitors of the latter two
      molecules. CONCLUSION: The induction of ICAM-1 by infection of umbilical vein
      endothelial cells with P. gingivalis might be mediated through the NF-kappaB
      pathway, but not by the p38 MAPK pathway.

PMID- 20825556
TI  - Tumour necrosis factor-alpha promoter region polymorphisms affect the course of
      spontaneous HBsAg clearance.
AB  - BACKGROUND: This study aimed to investigate the roles of tumour necrosis factor
      alpha (TNF-alpha) gene polymorphisms in the spontaneous clearance of HBsAg after
      a hepatitis B virus (HBV) infection. METHODS: Polymorphisms in the TNF-alpha (
      1031 T to C, -863 C to A, -857 C to T, -308 G to A and -238 G to A transition)
      gene were evaluated in 274 chronic HBV-infected patients and 194 patients with
      resolved HBV infection. The peripheral blood mononuclear cells (PBMC) isolated
      from 77 (28%) of the 274 chronic HBV-infected patients with negative HBeAg and
      positive antibody to HBeAg were stimulated with HBcAg. Data on TNF-alpha
      genotypes and phenotypes in subjects with/without the A allele at the TNF-alpha
      863 promoter single nucleotide polymorphism (rs1800630) were compared. RESULTS:
      The A allele in the -863 promoter region of the TNF-alpha gene was present in 154
      (56.2%) chronic HBV-infected patients and 87 (44.8%) patients who recovered from
      HBV infection (odds ratio 1.58; P<0.01). The TNF-alpha-863 A allele genotype
      predicted lower TNF-alpha production by PBMC after in vitro HBcAg stimulation
      (P<0.02). CONCLUSIONS: The A allele at the -863 locus of the promoter region of
      the TNF-alpha gene predicts lower HBcAg-inducible TNF-alpha secretion. It is also
      associated with chronicity of HBV infection.

PMID- 20825557
TI  - Parallel microRNA and mRNA expression profiling of (genotype 1b) human hepatoma
      cells expressing hepatitis C virus.
AB  - BACKGROUND & AIMS: MicroRNAs (miRNAs) are members of a class of small noncoding
      functional RNAs that modulate gene regulation at the post-transcriptional level
      in a sequence specific manner. miRNA dysfunction has been linked to the
      pathophysiology of human diseases including those resulting from viral
      infections. The objective of this study was to investigate changes in miRNA
      profiles that occur in hepatoma cells expressing hepatitis C virus (HCV) and
      identify anticorrelated mRNAs, which may be their regulatory targets. METHODS:
      Microarrays were used to perform global miRNA and mRNA expression analysis. Fold
      changes and pairwise statistics were computed for the resulting datasets.
      Hierarchical cluster and pathway analyses were performed to assess the degree of
      differential expression and identify regulatory networks. Bioinformatics tools
      were used to integrate mRNA profiling results with miRNA target predictions.
      RESULTS: Replication of the Con1 strain of HCV virus in hepatoma cells elicited
      extensive differential expression of both miRNAs and mRNAs. Forty-three
      differentially expressed miRNAs (P<=0.001) were identified by microarray analysis
      in HCV expressing cells. Six thousand eight hundred and fifteen differentially
      expressed mRNAs (P<=0.05) were identified. Computational analyses revealed
      anticorrelated miRNA:mRNA pairs for each target prediction algorithm used.
      Pathway analysis generated a filtered pathway with 120 entities, including seven
      major regulators and nine major targets potentially under the control of at least
      11 miRNAs. CONCLUSIONS: The expression of a number of anticorrelated miRNAs:mRNA
      pairs are affected by the presence of HCV. These miRNAs and their putative
      targets are attractive candidates for being involved in the pathogenesis and/or
      progression of HCV-induced chronic hepatitis.

PMID- 20825558
TI  - Hepatotoxicity of khat chewing.

PMID- 20825559
TI  - Anti-oxidants do not prevent bile acid-induced cell death in rat hepatocytes.
AB  - BACKGROUND: Bile acids, reactive oxygen species (ROS) and inflammatory cytokines
      are crucial regulators of cell death in acute and chronic liver diseases. The
      contribution of each factor to hepatocyte death, either apoptosis or necrosis,
      has not been clarified as yet. It has been suggested that the generation of
      oxidative stress by bile acids contributes to hepatocyte death during cholestasis
      and bile acid toxicity, although the beneficial role of ROS prevention in bile
      acid-mediated cell death is not fully understood. AIM: Study the effects of anti
      oxidants in bile acid-induced cell death in vitro. METHODS: Primary rat
      hepatocytes were exposed to the bile acids glycochenodeoxycholic acid (GCDCA) or
      taurolithocholic acid-3 sulphate in the absence or presence of ROS scavengers or
      anti-oxidants. Haeme oxygenase (HO)-1 mRNA levels were analysed by quantitative
      polymerase chain reaction. Apoptosis was quantified by acridine orange staining
      and caspase-3 activity assay. Necrosis was detected by Sytox green staining.
      RESULTS: Anti-oxidants do not attenuate bile acid-induced cell death.
      Furthermore, bile acid exposure does not enhance the mRNA expression of the
      oxidative stress-responsive gene HO-1. The Src-kinase inhibitor, SU6656, does
      reduce GCDCA-induced apoptosis and necrosis. CONCLUSIONS: In hepatocytes, bile
      acid-induced toxicity is not prevented by scavengers of oxidative stress. The
      beneficial effects observed in patients might be because of the contribution of
      ROS and cytokines rather than bile acid-mediated oxidative stress. However, the
      use of specific Src kinase inhibitors might be a useful tool to prevent bile acid
      induced injury in liver diseases.

PMID- 20825560
TI  - Role of Toll-like receptor impairment in cirrhosis infection risk: are we making
      progress?

PMID- 20825561
TI  - TUNEL assay for identifying ablated myocardium.
AB  - The terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL)
      assay identifies apoptosis and is used in transplant pathology to detect cardiac
      allograft rejection. We illustrate the use of TUNEL in identifying segments of
      ablated ventricular myocardium, and discuss its advantages over conventional
      histopathological stains. The TUNEL assay can be useful to investigators of
      catheter ablation therapy.

PMID- 20825562
TI  - Ablation of atrioventricular nodal reentrant tachycardia in a patient with
      reversal of slow and fast pathways inputs into the atrioventricular node.
AB  - We report a case of atrioventricular nodal reentrant tachycardia (AVNRT)
      coexistent with His bundle anomaly and atrial septal defects. The His-bundle
      potential was recorded at the coronary sinus (CS) ostium. Fractionated atrial
      potentials and an A:V electrogram ratio 1:3 were recorded at the anterior septum
      of the tricuspid annulus approximately 2 cm from CS ostium. Radiofrequency
      catheter ablation at the anterior septum of the tricuspid annulus effectively
      eliminated AVNRT.

PMID- 20825564
TI  - 15. Discogenic low back pain.
AB  - An estimated 40% of chronic lumbosacral spinal pain is attributed to the discus
      intervertebralis. Degenerative changes following loss of hydration of the nucleus
      pulposus lead to circumferential or radial tears within the annulus fibrosus.
      Annular tears within the outer annulus stimulate the ingrowth of blood vessels
      and accompanying nociceptors into the outer and occasionally inner annulus.
      Sensitization of these nociceptors by various inflammatory repair mechanisms may
      lead to chronic discogenic pain. The current criterion standard for diagnosing
      discogenic pain is pressure-controlled provocative discography using strict
      criteria and at least one negative control level. The strictness of criteria and
      the adherence to technical detail will allow an acceptable low false positive
      response rate. The most important determinants are the standardization of
      pressure stimulus by using a validated pressure monitoring device and avoiding
      overly high dynamic pressures by the slow injection rate of 0.05 mL/s. A positive
      discogram requires the reproduction of the patient's typical pain at an intensity
      of > 6/10 at a pressure of < 15 psi above opening pressure and at a volume less
      than 3.0 mL. Perhaps the most important and defendable response is the failure to
      confirm the discus is symptomatic by not meeting this strict criteria. Various
      interventional treatment strategies for chronic discogenic low back pain
      unresponsive to conservative care include reduction of inflammation, ablation of
      intradiscal nociceptors, lowering intranuclear pressure, removal of herniated
      nucleus, and radiofrequency ablation of the nociceptors. Unfortunately, most of
      these strategies do not meet the minimal criteria for a positive treatment
      advice. In particular, single-needle radiofrequency thermocoagulation of the
      discus is not recommended for patients with discogenic pain (2 B-).
      Interestingly, a little used procedure, radiofrequency ablation of the ramus
      communicans, does meet the (2 B+) level for endorsement. There is currently
      insufficient proof to recommend intradiscal electrothermal therapy (2 B+/-) and
      intradiscal biacuplasty (0). It is advised that ozone discolysis, nucleoplasty,
      and targeted disc decompression should only be performed as part of a study
      protocol. Future studies should include more strict inclusion criteria.

PMID- 20825565
TI  - 14. Coccygodynia.
AB  - Coccygodynia is painful condition localized in the region of the coccyx. In most
      cases a traumatic etiology is present. In the idiopathic form other causes such
      as infections and tumor have to be excluded. Coccygodynia can also be the result
      of pain referred from visceral structures due to conditions such as disorders of
      the rectum, the colon sigmoideum, and the urogenital system. In case of a
      traumatic etiology the diagnosis is made based on the typical medical history
      whereby the pain is provoked by prolonged sitting and cycling. Lateral images of
      the coccyx are always indicated. The same is true for manual examination of the
      coccyx. In case of absence of provocation of the coccygeal pain by prolonged
      sitting and manual examination neurological causes such as lumbar disc hernias
      are a possible reason for the coccygodynia. In the acute phase the first choice
      of treatment are NSAIDs. Treatment for patients with severe pain in the chronic
      phase consists of manual therapy and/or a local injection of local anesthetic and
      corticosteroid into the painful segment (2 C+). Other interventional treatments
      such as intradiscal injections, ganglion impar block, radiofrequency treatment
      and caudal block are advised only under study conditions (0). Coccygectomy is not
      recommended because of long-term moderate results and the chance of major
      complications.

PMID- 20825566
TI  - Multiple large pilomatricomas in the setting of diffuse epidermal nevi.
AB  - Epidermal nevi are hamartomas arising from the embryonic ectoderm during early
      embryonic stages, resulting in cutaneous mosaicism. We describe a patient with
      diffuse epidermal nevi and multiple large pilomatricomas arising near or within
      epidermal nevi.

PMID- 20825567
TI  - Linear morhpea, nevus comedonicus, and lichen striatus in a 5-year-old girl.
AB  - Linear morphea, lichen striatus, and nevus comedonicus are rare conditions. We
      describe a five-year-old girl in whom all three of these dermatoses are present.

PMID- 20825568
TI  - Linear childhood discoid lupus erythematosus following the lines of Blaschko:
      successfully treated with topical tacrolimus.
AB  - The linear arrangement of discoid lupus erythematosus is uncommon. Here, we
      report a 6-year-old Japanese girl with linear discoid lupus erythematosus
      following the lines of Blaschko on her face and neck. Topical tacrolimus
      treatment improved the eruptions. The present case also indicated the important
      role of epidermal and dermal cells as well as immune cells in the pathogenesis of
      cutaneous lupus erythematodes.

PMID- 20825569
TI  - Rhabdoid tumor mimicking hemangioma.
AB  - We report a young boy with a malignant tumor, which remained unrecognized for 8
      months because it was assumed to be a hemangioma. The presentation of a rhabdoid
      tumor mimicking hemangioma is very rare. It was reported only on two earlier
      occasions. Rhabdoid tumors are one of the most aggressive types of malignancies
      encountered in pediatric oncology. It is important to recognize that a fast
      growing vascular lesion in a child will often be a hemangioma, but could also be
      an aggressive tumor.

PMID- 20825570
TI  - Nevus trichilemmocysticus: report of a new case of a recently recognized entity.
AB  - A new type of organoid epidermal nevus, characterized by the presence of multiple
      trichilemmal cysts disposed in a linear arrangement, was recently recognized and
      named nevus trichilemmocysticus. We report a 10-year-old girl with a congenital
      linear dermatosis affecting the head, neck, trunk, limbs, palms, and soles.
      Initially, the lesions that followed the lines of Blaschko consisted of yellowish
      plaques covered by verrucous papules and filiform hyperkeratoses. Additionally,
      since the age of 6 years, numerous cyst-like structures developed on the linear
      lesions involving the limbs. On histopathological examination, all of the excised
      cystic lesions were found to be trichilemmal cysts. Hence, we herein describe a
      new case of nevus trichilemmocysticus.

PMID- 20825571
TI  - Primary cutaneous anaplastic large cell lymphoma of the nasal tip in a child.
AB  - A 4-year-old boy with primary cutaneous anaplastic large cell lymphoma located on
      the nasal tip is presented. The lesion healed spontaneously in 4 months without
      any evidence of residual disease. Cutaneous anaplastic large cell lymphoma,
      though rare in children, may occur, and should be considered when a rapidly
      growing ulcerating skin lesion appears.

PMID- 20825572
TI  - Proportional Venn diagram and determinants of allergic respiratory diseases in
      Italian adolescents.
AB  - Large variations in prevalence of atopy and allergic diseases are reported
      worldwide in children, but in epidemiological studies the use of skin prick tests
      (SPT) and spirometry along with questionnaires is not common in the Mediterranean
      Area. The present work was aimed at evaluating the prevalence of current asthma
      (CA), rhinoconjunctivitis (RC), and eczema (E), with atopy and respiratory
      function, and the role of risk factors for allergic respiratory diseases. A total
      of 2150 Italian schoolchildren were cross-sectionally investigated through
      respiratory questionnaire, SPT, and spirometry. A proportional Venn diagram
      quantified the distribution of CA, RC, and E, stratifying for allergic
      sensitization to show differences in prevalence of allergic diseases among
      subjects with and without positive SPT. CA prevalence was 4.2%, RC 17.9%, and E
      5.3%. CA and RC increased, while E decreased, with respect to previous local
      studies. Allergic sensitization prevalence (evaluated as positive response to at
      least one SPT) was 39.2%. A double Venn diagram identified 15 categories. Atopic
      CA was threefold more frequent than non-atopic CA. Atopic vs non-atopic RC and E
      were 9.6% vs 10.3% and 2.0% vs 3.3%, respectively. Atopic vs non-atopic RC
      associated with CA were 1.6% vs 0.5%; the same figures for RC associated with E
      were 0.8% vs 1.3%. Asymptomatic atopic subjects were 27.0%. Atopy, RC, parental
      asthma, and environmental risk factors were associated with CA. Atopy and
      environmental factors were risk factors also for RC. Asthma and traffic exposure
      were linked to reduced lung function. Respiratory allergic diseases are still
      increasing and largely concomitant in Italian adolescents. Atopy is more
      important for CA than RC. Avoiding exposures to measured environmental risk
      factors would prevent 41% of current asthma and 34% of rhinoconjunctivitis.

PMID- 20825573
TI  - Lower urinary tract symptoms (LUTS) after renal transplant in non-urologic anuric
      patients.
AB  - We assessed LUTS at least 12 months after RTx in patients without evidence of
      lower urinary tract dysfunction (non-urologic) that had been anuric for at least
      six months before RTx. No bladder recycling was performed before RTx. LUTS were
      evaluated using a questionnaire. Clinical records were also reviewed. LUTS in
      anuric patients were compared with those in non-anuric patients. Fourteen anuric
      patients fulfilled the inclusion criteria. Median age at RTx was 11 (5-21) yr,
      median duration of anuria before RTx 24 (7-46) months, and median post-RTx follow
      up 2.7 (1.9-10.2) yr. Daytime symptoms were exceptional. Nocturia was the most
      common symptom (10 patients). Only one patient reported symptoms to affect her
      quality of life. One patient experienced a febrile UTI and none graft failure.
      LUTS (nocturia) proved unrelated to duration of anuria, length of follow-up, and
      presence of (nocturnal) polyuria. LUTS were not statistically different in
      patients anuric and non-anuric before RTx. Non-urologic patients suffer from long
      term storage symptoms, particularly nocturia. LUTS, however, do not seem to
      increase the risks of urinary infections or graft failure and appear to occur
      irrespective of the presence of anuria before RTx. Bladder recycling before RTx
      seems unnecessary.

PMID- 20825574
TI  - Successful bone marrow transplantation for children with aplastic anemia based on
      a best-available evidence strategy.
AB  - A best-available evidence strategy, i.e., the best-available donors,
      conditioning regimens and GVHD prophylaxis were chosen at the time of BMT for AA,
      was analyzed retrospectively. The outcomes for 18 children with AA who underwent
      allogeneic BMT were analyzed. The median age was 11 yr (range 4-16), and nine
      were men. As conditioning regimens, seven had low-dose irradiation + CY, six had
      ATG + CY + Flu, and five had ATG + CY. Donors were HLA-matched siblings in 10,
      HLA-mismatched family in one, HLA-matched unrelated in three, and HLA-mismatched
      unrelated in four. As GVHD prophylaxis, three received CsA alone, nine received
      CsA + MTX, and six received tacrolimus + MTX. All 18 patients showed engraftment.
      The median number of days until the neutrophil count exceeded 500/MUL was 16
      (range 11-21) post-transplant. Five developed more than grade 2 acute GVHD, and
      three developed extensive cGVHD. One patient died because of interstitial
      pneumonia complicated with cGVHD. Five-yr OS was 94% (95% CI: 83-105). These
      results suggest that a strategy of treating patients based on the best-available
      evidence is acceptable.

PMID- 20825575
TI  - Endoscopic treatment of pediatric living donor liver transplant biliary-enteric
      stricture with small-caliber guidewire and angioplasty balloon.

PMID- 20825576
TI  - Drought limitation of photosynthesis differs between C3and C4grass species in a
      comparative experiment.
AB  - Phylogenetic analyses show that C4 grasses typically occupy drier habitats than
      their C3 relatives, but recent experiments comparing the physiology of closely
      related C3 and C4 species have shown that advantages of C4 photosynthesis can be
      lost under drought. We tested the generality of these paradoxical findings in
      grass species representing the known evolutionary diversity of C4 NADP-me and C3
      photosynthetic types. Our experiment investigated the effects of drought on leaf
      photosynthesis, water potential, nitrogen, chlorophyll content and mortality. C4
      grasses in control treatments were characterized by higher CO2 assimilation rates
      and water potential, but lower stomatal conductance and nitrogen content. Under
      drought, stomatal conductance declined more dramatically in C3 than C4 species,
      and photosynthetic water-use and nitrogen-use efficiency advantages held by C4
      species under control conditions were each diminished by 40%. Leaf mortality was
      slightly higher in C4 than C3 grasses, but leaf condition under drought otherwise
      showed no dependence on photosynthetic-type. This phylogenetically controlled
      experiment suggested that a drought-induced reduction in the photosynthetic
      performance advantages of C4 NADP-me relative to C3 grasses is a general
      phenomenon.

PMID- 20825577
TI  - OsRAN2, essential for mitosis, enhances cold tolerance in rice by promoting
      export of intranuclear tubulin and maintaining cell division under cold stress.
AB  - With global climate change, abnormally low temperatures have affected the world's
      rice production. Many genes have been shown to be essential for molecular
      improvement of rice cold-tolerance traits. However, less is known about the
      molecular cellular mechanism of their response to cold stress. Here, we
      investigated OsRAN2 involved in regulation of cell division during cold stress in
      rice. Expression of OsRAN2 was increased under cold treatment, but not during
      salt and drought stress. The mean root mitotic index was closely related to the
      expression level of OsRAN2. Knockdown transgenic rice lines showed an aberrant
      organization of spindles during mitosis and stunted growth during development.
      Overexpression of OsRAN2 enhanced cold tolerance in rice. The transgenic rice
      overexpressing OsRAN2 showed maintained cell division, decreased proportion of
      cells with intranuclear tubulin and formation of a normal nuclear envelope under
      the cold condition. Our study suggests a mechanism for OsRAN2 in regulating cold
      resistance in rice by maintaining cell division through promoting the normal
      export of intranuclear tubulin at the end of mitosis. This insight could help
      improve the cold-tolerance trait in rice.

PMID- 20825578
TI  - Drought increases freezing tolerance of both leaves and xylem of Larrea
      tridentata.
AB  - Drought and freezing are both known to limit desert plant distributions, but the
      interaction of these stressors is poorly understood. Drought may increase
      freezing tolerance in leaves while decreasing it in the xylem, potentially
      creating a mismatch between water supply and demand. To test this hypothesis, we
      subjected Larrea tridentata juveniles grown in a greenhouse under well-watered or
      drought conditions to minimum temperatures ranging from -8 to -24  degrees C. We
      measured survival, leaf retention, gas exchange, cell death, freezing point
      depression and leaf-specific xylem hydraulic conductance (k1). Drought-exposed
      plants exhibited smaller decreases in gas exchange after exposure to -8  degrees
      C compared to well-watered plants. Drought also conferred a significant positive
      effect on leaf, xylem and whole-plant function following exposure to -15  degrees
      C; drought-exposed plants exhibited less cell death, greater leaf retention,
      higher k1 and higher rates of gas exchange than well-watered plants. Both drought
      exposed and well-watered plants experienced 100% mortality following exposure to 
      24  degrees C. By documenting the combined effects of drought and freezing
      stress, our data provide insight into the mechanisms determining plant survival
      and performance following freezing and the potential for shifts in L. tridentata
      abundance and range in the face of changing temperature and precipitation
      regimes.

PMID- 20825579
TI  - Nitrogen source interacts with ROP signalling in root hair tip-growth.
AB  - Root hairs elongate in a highly polarized manner known as tip growth.
      Overexpression of constitutively active Rho of Plant (ROP)/RAC GTPases mutants
      induces swelling of root hairs. Here, we demonstrate that Atrop11(CA)-induced
      swelling of root hairs depends on the composition of the growth medium. Depletion
      of ammonium allowed normal root hair elongation in Atrop11(CA) plants, induced
      the development of longer root hairs in wild-type plants and suppressed the
      effect of Atrop11(CA) expression on actin organization and reactive oxygen
      species distribution, whereas membrane localization of the protein was not
      affected. Ammonium at concentrations higher than 1 mM and the presence of nitrate
      were required for induction of swelling. Oscillations in wall and cytoplasmic pH
      are known to accompany tip growth in root hairs, and buffering of the growth
      medium decreased Atrop11(CA)-induced swelling. Fluorescence ratio imaging
      experiments revealed that in wild-type root hairs, the addition of NH4NO3 to the
      growth medium induced an increase in the amplitude of extracellular and
      intracellular pH oscillations and an overall decrease in cytoplasmic pH at the
      cell apex. Based on these results, we suggest a model in which ROP GTPases and
      nitrogen-dependent pH oscillations function in parallel pathways, creating a
      positive feedback loop during root hair growth.

PMID- 20825580
TI  - Selective suppression of the incorrect response implementation in choice behavior
      assessed by transcranial magnetic stimulation.
AB  - Selecting the adequate alternative in choice situations may involve an inhibition
      process. Here we assessed response implementation during the reaction time of a
      between-hand choice task with single- or paired-pulse (3 or 15 ms interstimulus
      intervals [ISIs]) transcranial magnetic stimulation of the motor cortex. The
      amplitude of the single-pulse motor evoked potential (MEP) initially increased
      for both hands. At around 130 ms, the single-pulse MEP kept increasing for the
      responding hand and decreased for the nonresponding hand. The paired-pulse MEP
      revealed a similar pattern for both ISIs with no effect on short intracortical
      inhibition and intracortical facilitation measures. The results suggest that the
      incorrect response implementation was selectively suppressed before execution of
      the correct response, preventing errors in choice context. The results favor
      models assuming that decision making involves an inhibition process.

PMID- 20825581
TI  - Early pregnancy detection of Iraqi riverine buffalo (Bubalus bubalis) using the
      BioPRYN enzyme-linked immunosorbent assay for PSPB and the progesterone assay.
AB  - This study was undertaken to detect pregnancy in Iraqi riverine buffalo (Bubalus
      bubalis) using three different methods (rectal palpation, plasma progesterone
      concentration and detection of the presence of pregnancy-specific protein B
      (PSPB) with the BioPRYN((r)) enzyme-linked immunosorbent assay (ELISA) test. The
      aim of the study was to identify the most sensitive, early and accurate method
      for detecting pregnancy. Twenty-two female riverine buffalo that were 6.0 +/-
      0.93 years old were used. Four blood samples per buffalo were taken via jugular
      venipuncture at days 22-24, 32-34, 42-44 and 58-61 post-mating (PM) to measure
      the progesterone concentration (ng/ml) and to detect the presence of plasma PSPB.
      The rectal palpation method was employed to evaluate all buffalo on days 42-44
      and 58-61 PM. The BioPRYN((r)) test differed (p<0.01) from the other tests with
      earlier accuracy for detecting pregnant and non-pregnant buffalo. Eighty-eight
      percent of pregnant and 76.9% of non-pregnant buffalo were distinguished early
      (days 22-24 PM) using BioPRYN((r)) and plasma PSPB-ELISA level (2.09 +/- 0.12
      ng/ml) in relation to 66.7% and 53.9% detected using the progesterone assay at
      similar days (4.30 +/- 0.40 ng/ml). In conclusion, these results described, for
      the first time, the early and accurate pregnancy detection of water riverine
      buffalo using BioPRYN((r)) technology and provided the plasma levels of PSPB
      using an ELISA test. These findings will improve the reproductive and productive
      efficiency of Iraqi riverine buffalo by adapting the recent management and
      reproductive strategies in Iraq and in the world.

PMID- 20825582
TI  - Expression of the vascular endothelial growth factor (VEGF-A) and its receptors
      in the umbilical cord in the course of pregnancy in the pig.
AB  - The umbilical cord (UC) and the placenta are important organs through which
      respiratory gases, nutrients, wastes and biologically active substances are
      exchanged between the maternal and the foetal system. A rapid placental
      vascularization observed in the second half of pig pregnancy is positively
      correlated with the mRNA expression of the vascular endothelial growth factor
      (VEGF). Based on these findings, we hypothesized that VEGF may have a stimulatory
      effect in the dynamically growing UC. To further understand the role of the VEGF
      VEGFR system during UC development, mRNA and protein expression as well as the
      cellular localization of VEGF-A, VEGFR-1 and VEGFR-2 in UC were examined on days
      40, 60, 75 and 90 of pregnancy and after physiological delivery in the pig (day
      114 of pregnancy). Real Time RT-PCR analysis showed an increase in the mRNA
      levels of VEGF120 and VEGF164 from day 90 of pregnancy. VEGFR-1 mRNA expression
      was significantly increased on day 75 of pregnancy. No significant changes in
      VEGFR-2 mRNA expression were detected. In turn, western blot analysis revealed an
      increase in VEGF-A protein expression on day 40, compared to the later days of
      pregnancy. A rapid increase in the VEGFR-1 protein level was noted on day 75 and
      90 of gestation. No significant changes in VEGFR-2 protein expression were
      detected on any of the analysed days of pregnancy. Immunohistochemical staining
      enabled detection of VEGF-VEGFR system, in endothelial and tunica media cells of
      the umbilical vessels and in allantoic duct and amniotic epithelium on all
      analysed days of pregnancy. Positive reactions for VEGF-A and VEGFR-1, but not
      VEGFR-2, were also observed in myofibroblasts. In conclusion, this data shows
      that members of the VEGF-VEGFR system are temporally and spatially well localized
      for playing key roles during umbilical cord formation and its intensive growth
      observed after day 75 of pregnancy.

PMID- 20825583
TI  - Selected metabolic and hormonal profiles during maintenance of spontaneous
      ovarian cysts in dairy cows.
AB  - Information is lacking regarding the relationship between metabolic and hormonal
      profiles and the maintenance of spontaneous ovarian cyst disease in dairy cows.
      For this reason, the concentrations of non-esterified fatty acids (NEFA), insulin
      like growth factor I (IGF-I) and cortisol (C) were investigated during the
      spontaneous course of ovarian cyst disease in dairy cows (n=6) between the 7th
      and 16th weeks post-partum (PP). The control group consisted of normally cycling
      cows (n=6). Blood samples were collected twice a day, and plasma was analysed
      using different techniques. Progesterone and 15-ketodihydro-PGF(2alpha) plasma
      profiles were investigated to confirm the ovulatory or anovulatory conditions of
      the cows. Cortisol plasma levels were not significantly different among sampling
      times within each group or between the two groups. NEFA plasma levels were
      significantly higher in cycling cows compared to cystic cows at the 16th week PP
      (p<0.01), but with rather low values, indicating by now sparse mobilization of
      fat stores. Insulin-like growth factor I plasma concentrations were higher in
      cystic cows during the 8th, 10th, 11th (p<0.01) and 16th week PP (p<0.05),
      indicating that the presence of ovarian cysts coincides with increased IGF-I
      levels. These results suggest no influence of cortisol and NEFA levels in cysts
      maintenance, while a possible involvement of IGF-I can be suspected not only in
      the pathogenesis, as already known, but also in the maintenance of spontaneous
      cystic ovarian disease in cattle.

PMID- 20825584
TI  - Selected ovarian ultrasonographic characteristics during vernal transition are
      useful to estimate time of first ovulation of the year.
AB  - It is important to get mares pregnant as early as possible after vernal
      transition and thus, identification signs of impending 1st ovulation of the year
      are warranted. To identify clinical indicators of an approaching first ovulation
      of the year, mares were teased with a stallion for oestrous detection starting
      January 3 and subjected to ultrasonographic examination. Day of first appearance
      of uterus oedema, follicular wall invagination, intrafollicular echogenicity,
      double contour of the follicle wall, increase in granulosa thickness, follicular
      wall hyperechogenicity and appearance of pear-shaped follicles was registered, as
      well as follicle diameter and number. Seventy per cent of the mares had
      anovulatory oestrous periods of 4.6 +/- 3.6 days, with an interoestroual interval
      of 12.5 +/- 12.2 days. Number of anovulatory oestruses per mare was 2.4 +/- 2.3.
      Uterine oedema occurred in 77% of the mares, 32.4 +/- 25.6 days before ovulation.
      Invagination of the follicular wall appeared in 44.4% of the animals, 24.5 +/-
      18.4 days before ovulation. Intrafollicular echogenicity was seen in all mares
      and double contour of the follicle was seen in 77% of the animals. Both last two
      characteristics appeared 1-72 days before ovulation. Increased thickness of the
      granulosa occurred in 66% of the mares, 1-19 days before ovulation. Pear-shaped
      follicles and follicular wall hyperechogenicity were detected 3 or less days
      before the first ovulation, in 44.4% and 55.5% of mares, respectively. Mean
      number of follicles > 15 mm decreased at least 16 days before ovulation. We
      concluded that no isolated characteristic was a reliable indicator. However,
      increase in granulosa thickness, formation of a pear-shaped follicle and
      follicular wall hyperechogenicity, associated with the reduction of the number of
      follicles > 15 mm in diameter to < 3, resulted in the first ovulation of the year
      in 44-67% of the transitional mares, 1-19 days after the characteristics
      appeared.

PMID- 20825585
TI  - Activation of zona-free buffalo (Bubalus bubalis) oocytes by chemical or
      electrical stimulation, and subsequent parthenogenetic embryo development.
AB  - Parthenogenetic activation using zona-free oocytes offers an alternative model
      that could be applied to develop protocols for the activation of reconstructed
      embryos for cloning. The aim of this study was to compare the efficacy of
      different methods for the activation of zona-free buffalo oocytes in terms of
      their effects on the developmental competence of parthenogenetic embryos. The
      effects of zona removal on parthenogenetic activation and in vitro developmental
      competence of metaphase II oocytes were also examined. All activation methods
      were followed by incubation of 2 mm 6-dimethylaminopurine (6-DMAP) for 4 h. Out
      of three different pulse strengths (1.2, 2.1 or 3.3 kV/cm) used, 2.1 kV/cm
      resulted in the highest blastocyst rate (25.3%). On comparing different chemical
      agents and electric pulse, highest blastocyst rate was observed for calcium
      ionophore (CaI) (28.6%) followed by ethanol (25.0%), electric pulse (22.5%) and
      combined CaI and ethanol treatment (16.7%) although differences among them were
      not significant. Furthermore, a significantly reduced developmental potential was
      observed in zona-free oocytes when compared to zona-intact ones up to the
      blastocyst stage (44.3% vs 27.1%). In conclusion, zona-free buffalo oocytes can
      be successfully activated for parthenogenetic development using chemical or
      electrical stimulation. Out of different agents examined, CaI followed by 6-DMAP
      resulted in the highest blastocyst rate.

PMID- 20825586
TI  - High embryonic recovery rates with in vivo and ex vivo techniques in the bitch.
AB  - The embryonic collection techniques in dogs present a vast methodological
      variation and low recovery rates. The objectives were to compare and describe two
      techniques as to the recovery of canine embryos, on the 12th day after the first
      mating or artificial insemination. Embryos were recovered through uterine horn
      flushing in vivo, before performing the ovariohysterectomy (OHE) (Group 1; n = 9)
      or ex vivo, immediately after the OHE (Group 2; n = 9). In total, 43 and 47
      embryonic structures were recovered in Groups 1 and 2, respectively. There was no
      significant difference (p > 0.05) between groups on recovery rates (72.8% and
      81.0%, respectively). We inferred that both in vivo and ex vivo techniques allow
      a high rate of embryonic recovery; in the collection technique prior to the OHE,
      it is essential to carefully handle the reproductive system during the trans
      surgical period and that the 12th day (D12) after the first mating/artificial
      insemination is an efficient option for the high recovery rate of morulae and
      blastocysts.

PMID- 20825587
TI  - Deleterious effects of progestagen treatment in VEGF expression in corpora lutea
      of pregnant ewes.
AB  - The aim of the current study was to determine the possible effects of progestagen
      oestrous synchronization on vascular endothelial growth factor (VEGF) expression
      during sheep luteogenesis and the peri-implantation period and the relationship
      with luteal function. At days 9, 11, 13, 15, 17 and 21 of pregnancy, the ovaries
      from 30 progestagen treated and 30 ewes cycling after cloprostenol injection were
      evaluated by ultrasonography and, thereafter, collected and processed for
      immunohistochemical evaluation of VEGF; blood samples were drawn for evaluating
      plasma progesterone. The progestagen-treated group showed smaller corpora lutea
      than cloprostenol-treated and lower progesterone secretion. The expression of
      VEGF in the luteal cells increased with time in the cloprostenol group, but not
      in the progestagen-treated group, which even showed a decrease between days 11
      and 13. In progestagen-treated sheep, VEGF expression in granulosa-derived
      parenchymal lobule capillaries was correlated with the size of the luteal tissue,
      larger corpora lutea had higher expression, and tended to have a higher
      progesterone secretion. In conclusion, the current study indicates the existence
      of deleterious effects from exogenous progestagen treatments on progesterone
      secretion from induced corpora lutea, which correlate with alterations in the
      expression of VEGF in the luteal tissue and, this, presumably in the processes of
      neoangiogenesis and luteogenesis.

PMID- 20825588
TI  - Incidence and prevention of early parturition in sows.
AB  - A retrospective study, based on 60,990 farrowing records from 35 commercial
      herds, was performed to determine the incidence of early parturition (<114 d) and
      to investigate the relationship between early parturition and total number of
      piglets born, number of piglets born alive and percentage of stillborn piglets
      per litter. The mean gestation length was 115.4 +/- 1.62 d, and early parturition
      occurred in 10% of all farrowing records. Sows with early parturition had
      significantly more stillborn piglets and a larger litter size compared to sows
      with a normal gestation length (114-117 d). Sows with a gestation length <114 d
      were 1.2 times (95% CI: 1.19-1.21; p<0.001) more likely to have an early
      parturition at the subsequent parity. A second study was performed in four herds
      (n=329) to investigate the efficacy of altrenogest administration on 110-112 d
      (T112) or 111-113 d (T113) of gestation for preventing early parturition and to
      investigate the effect of this treatment on the reproductive performance of sows.
      The interval between the last altrenogest treatment and the onset of parturition
      was 3.3 +/- 1.32 (T112) or 2.0 +/- 0.89 (T113) days. The gestation length of sows
      of the altrenogest group (T112 + T113) (115.3 +/- 1.23 d) was significantly
      longer compared to gestation length of the non-treated sows (114.7 +/- 1.69d)
      (p<0.01). Altrenogest treatment had no negative effect on the reproductive
      performances of the sows. In conclusion, the administration of altrenogest in
      late gestation is an effective and safe method to prevent early parturition and
      can counteract the reproductive losses because of premature farrowing, which may
      occur in a substantial part of the farrowing events.

PMID- 20825589
TI  - Trends in global warming and evolution of nucleoproteins from influenza A viruses
      since 1918.
AB  - Global warming affects not only the environment where we live, but also all
      living species to different degree, including influenza A virus. We recently
      conducted several studies on the possible impact of global warming on the protein
      families of influenza A virus. More studies are needed in order to have a full
      picture of the impact of global warming on living organisms, especially its
      effect on viruses. In this study, we correlate trends in global warming with
      evolution of the nucleoprotein from influenza A virus and then analyse the trends
      with respect to northern/southern hemispheres, virus subtypes and sampling
      species. The results suggest that global warming may have an impact on the
      evolution of the nucleoprotein from influenza A virus.

PMID- 20825590
TI  - Mycobacterium tuberculosis infection of a native polycystic kidney following
      renal transplantation.
AB  - Tuberculosis is a recognized complication following renal transplantation.
      Patients with autosomal-dominant polycystic kidney disease are increasingly being
      offered renal transplantation as an alternative to chronic hemodialysis. These
      patients are uniquely susceptible to serious upper urinary tract infections that
      are associated with significant morbidity and mortality. While involvement with
      gram-negative organisms is well described, mycobacterial infection of native
      polycystic kidneys after transplantation has not been addressed. We report a case
      of a renal transplant recipient who suffered an isolated Mycobacterium
      tuberculosis infection of a native polycystic kidney. With a 4-drug anti
      tuberculosis therapy (ATT) regimen, the patient responded and became afebrile 8
      weeks after initiation of drug therapy. ATT was continued for a total of 1 year.
      Two years after completion of ATT, the patient enjoys a normal life and has
      stable graft function. M. tuberculosis, though not common, must be recognized as
      a potential source of infection of native polycystic kidneys in immunocompromised
      transplant recipients. Similar to the pattern observed with more common
      pathogens, these infections may be difficult to eradicate with standard
      antimicrobial drug regimens.

PMID- 20825591
TI  - Renal allograft failure due to emphysematous pyelonephritis: successful non
      operative management and proposed new classification scheme based on literature
      review.
AB  - Emphysematous pyelonephritis (EPN) is a rare necrotizing infection of the kidney
      caused by gas-forming organisms, usually occurs in diabetic patients, and often
      requires nephrectomy for effective therapy. EPN is rarely reported in renal
      allografts, with only 20 cases found in the English literature. We report herein
      a case of EPN in a transplanted kidney resulting in acute renal failure and
      sepsis. The patient was managed non-operatively with subsequent recovery of renal
      allograft function. Based on this experience and a review of the literature, we
      suggest an amended classification system for EPN in kidney transplantation to
      plan and guide treatment options accordingly. However, the scarcity of this
      disease process, coupled with the lack of prospective validation of the new
      classification scheme, prevents drawing definitive conclusions regarding optimal
      management strategies including the role and timing of allograft nephrectomy.

PMID- 20825592
TI  - Skin diseases in the alpaca (Vicugna pacos): a literature review and
      retrospective analysis of 68 cases (Cornell University 1997-2006).
AB  - This retrospective study describes 68 alpacas with skin diseases investigated
      from 1997 through 2006 at Cornell University. During this time period, 40 of 715
      (5.6%) alpacas presented to the university hospital had dermatological diseases.
      In addition, skin-biopsy specimens accounted for 86 of 353 (24.4%) of alpaca
      biopsy specimens submitted to the diagnostic laboratory, and of these 86
      specimens, follow-up was available for 28 cases. The following diseases were most
      common: bacterial infections (22%); neoplasms, cysts and hamartomas (19%);
      presumed immunological disorders (12%); and ectoparasitisms (10%). Conditions
      described for the first time included intertrigo, collagen and hair follicle
      hamartomas, lymphoma, hybrid follicular cysts, melanocytoma, anagen defluxion,
      telogen defluxion, presumed insect-bite hypersensitivity, ichthyosis, and
      possible hereditary bilateral aural haematomas and chondritis. The results of the
      retrospective study are compared and contrasted with the results of a literature
      review.

PMID- 20825593
TI  - Platelet-rich fibrin constructs elute higher concentrations of transforming
      growth factor-beta1 and increase tendon cell proliferation over time when
      compared to blood clots: a comparative in vitro analysis.
AB  - OBJECTIVE: To compare the concentration of a representative growth factor
      (transforming growth factor-beta [TGF-beta]1) eluted from a platelet-rich fibrin
      matrix (PRFMatrix), a platelet-rich fibrin membrane (PRFMembrane), and a whole
      blood clot (BC) over time, and to compare the mitogenic effect of the eluents
      from each construct. STUDY DESIGN: In vitro study. SAMPLE POPULATION: PRFMatrix,
      PRFMembrane, and BC (n=4/construct/time point). METHODS: Each construct was
      placed in tissue culture wells containing media for 7 days. The media was
      collected and replenished on days 1, 3, 5, and 7 and the concentration of eluted
      TGF-beta1 was measured by enzyme-linked immunosorbent assay. Canine tendon cells
      were subjected to additional aliquots of the conditioned media and the amount of
      cell proliferation compared. RESULTS: The media from both PRFM (PRFMatrix and
      PRFMembrane) constructs contained significantly more (P<=.026) TGF-beta1 at days
      1 and 3 and produced a significant increase (P<=.044) in cell proliferation at
      all time points compared with the BC. The PRFMembrane media contained
      significantly more (P<=.05) TGF-beta1 at days 1 and 3 and produced a significant
      increase (P<=.002) in cell proliferation at all time points compared with the
      PRFMatrix. CONCLUSIONS: Both PRFM constructs are comprised of a dense fibrin
      scaffold that contains increased concentrations of TGF-beta1 and are capable of
      increasing tendon cell proliferation over time when compared with a BC. CLINICAL
      RELEVANCE: The sustained increase in growth factor availability in PRFM
      constructs may be beneficial in the healing of biologically compromised tissues.

PMID- 20825594
TI  - In vitro mechanical comparison of 2.0 and 2.4 limited-contact dynamic compression
      plates and 2.0 dynamic compression plates of different thicknesses.
AB  - OBJECTIVE: To compare the bending structural stiffness and bending strength of
      thick and thin 2.4 mm limited contact dynamic compression plates (2.4 LC-DCP),
      2.0 mm LC-DCP (2.0 LC-DCP), and 2.0 dynamic compression plates (2.0 DCP). STUDY
      DESIGN: In vitro mechanical study. METHODS: Two thicknesses of 2.4 LC-DCP, 2.0 LC
      DCP, and 2.0 DCP stainless-steel plates were tested in 4-point bending. Data were
      collected during bending until implants plastically deformed. Bending structural
      stiffness and bending strength were determined from load displacement curves.
      Mechanical properties were compared between plates and the effects of plate type,
      size, and thickness on stiffness and strength were assessed using ANOVA. RESULTS:
      The thick 2.4 LC-DCP implant was the stiffest and strongest; the thin 2.0 DCP
      implant was most compliant and weakest. Larger sized plates, thicker plates, and
      limited contact design of plates enhanced stiffness and strength. For the plates
      studied, plate size had a larger effect than plate type or thickness on stiffness
      and strength. CONCLUSION: Increasing the size (width) and thickness of plates
      increases both the bending structural stiffness and strength. For the plates
      studied, LC-DCP implants were stiffer and stronger than DCP implants. CLINICAL
      RELEVANCE: Plate bending structural stiffness and strength can be most
      effectively enhanced by using a larger sized plate, but gains can also be
      achieved by using a thicker plate and/or an LC-DCP instead of a DCP implant when
      possible.

PMID- 20825595
TI  - Saline volume necessary to achieve predetermined intraluminal pressures during
      leak testing of small intestinal biopsy sites in the dog.
AB  - OBJECTIVE: To determine the volume of saline needed to achieve targeted
      intraluminal pressures during leak testing of closed jejunal biopsy sites in the
      dog. STUDY DESIGN: Experimental. ANIMALS: Dogs (n=38). METHODS: Jejunal biopsies
      in dogs were performed and closed using 3-4 full thickness simple interrupted
      sutures. Saline volumes needed to achieve 2 predetermined intraluminal pressures
      (20 and 34 cm water [15 and 25 mmHg]) in a 10 cm canine jejunal segment
      containing a closed biopsy site using 2 methods of luminal occlusion were
      recorded. RESULTS: The 95% confidence intervals for the volume of saline needed
      to achieve 20 and 34 cm water intraluminal pressure were 10.9-13.6 and 16.3-19.0
      mL, respectively with digital occlusion and 8.5-11.1 and 12.1-14.8 mL,
      respectively with Doyen occlusion. Correlation between volume of saline instilled
      and the pressure achieved was 0.76 for digital occlusion and 0.86 for Doyen
      occlusion. CONCLUSION: Correlation between volume of saline instilled and
      pressure achieved was greater with Doyen than digital occlusion. CLINICAL
      RELEVANCE: For canine jejunum, saline volumes of 16.3-19 mL (digital occlusion)
      and 12.1-14.8 mL (Doyen occlusion) can be used to achieve intraluminal pressures
      of 34 cm water during leak testing of a 10 cm segment containing a closed biopsy
      site.

PMID- 20825596
TI  - Relationships of body weight, body size, subject velocity, and vertical ground
      reaction forces in trotting dogs.
AB  - OBJECTIVE: To evaluate the relationship of body weight (BW) and size, dog
      velocity, and vertical ground reaction forces (GRF) from a large number of dogs
      of various sizes. STUDY DESIGN: Clinical research. ANIMALS: Orthopedically
      healthy dogs (n=129) METHODS: BW and dog size, represented as height at the
      withers (WH), were obtained. Stance times (ST), vertical impulses (VI), and peak
      vertical forces (PVF) of thoracic and pelvic limbs were measured on a force plate
      at controlled trotting speed. They were evaluated against BW and WH using linear
      regression analysis in absolute (nonnormalized) values, and when normalized to BW
      and/or body size according to the theory of dynamic similarity. Relative
      velocities were calculated for each dog. RESULTS: Absolute ST, VI, and PVF showed
      strong positive correlations with BW and/or body size. When GRFs were normalized
      to BW, correlations with body size were markedly reduced, but remained positive
      for VI, and turned negative for PVF. Normalizing the time-dependent variables (ST
      and VI) also to WH eliminated most size influence. A small dependency of fully
      normalized GRF on body size remained that was because of differences in relative
      velocity between dogs of different sizes. Reference values for the fully
      normalized data are given. CONCLUSIONS: The inherent relationship between BW,
      body size, dog velocity, and vertical GRF was demonstrated. CLINICAL RELEVANCE:
      BW, body size, and relative dog velocity must be accounted for when wanting to
      obtain GRF variables that are comparable between different dogs.

PMID- 20825597
TI  - Right dorsal colon resection and bypass for treatment of right dorsal colitis in
      a horse.
AB  - OBJECTIVE: To describe a novel surgical technique for management of right dorsal
      colitis in the horse. STUDY DESIGN: Clinical report. ANIMALS: 14-year-old
      Warmblood gelding. METHODS: The horse was referred for treatment of a stromal
      abscess and signs of right dorsal colitis. Plasma chemistry revealed marked
      hypoproteinemia. Abdominal ultrasonographic examination showed a thickened right
      dorsal colon (RDC). Medical treatment was unsuccessful. With the horse in left
      lateral recumbency under general anesthesia, an approach to the right side of the
      abdomen through a 16th rib resection was made. The thoracic cavity was entered
      during the approach. Surgical resection of the RDC and side-to-side anastomosis
      of the diaphragmatic flexure to the small colon (bypass) was performed. The
      thoracic cavity was closed by attaching the diaphragm to the body wall and air
      was removed at the completion of surgery. RESULTS: Resection of the RDC and
      bypass of the resected area was successfully performed. The colic signs and
      hypoproteinemia resolved. Complications of surgery included a deep surgical site
      infection with development of a large intrathoracic abscess. The abscess was
      managed with drainage and long-term antimicrobial treatment. CONCLUSION: Right
      dorsal colitis can be treated successfully with resection and bypass of the RDC.
      In cases where the thoracic cavity is penetrated during the abdominal approach,
      the diaphragm should be sutured to the body wall at the beginning of surgery to
      avoid development of an infection within the thoracic cavity. CLINICAL RELEVANCE:
      RDC resection and bypass may be an alternative approach for management of horses
      with right dorsal colitis.

PMID- 20825598
TI  - Detection of HHV-8 (human herpesvirus-8) genomes in induced peripheral blood
      mononuclear cells (PBMCs) from US blood donors.
AB  - BACKGROUND: Human herpesvirus-8 (HHV-8) causes Kaposi's sarcoma and can be
      detected and induced in peripheral blood mononuclear cells (PBMCs) from infected
      individuals. The prevalence of viral genomes in induced/cultured PBMCs from
      healthy blood donors has not been systematically studied. MATERIALS AND METHODS:
      PBMCs from 164 donors were purified and stored as two equal aliquots in liquid
      nitrogen. One aliquot was used for CD19+ B-cell purification with a fraction
      reserved for DNA extraction. The second aliquot was cultured for 2 or 4 days in
      culture media containing n-butyrate and tetradecanoyl phorbol acetate. DNA was
      extracted from all four cell sources: PBMCs, purified B cells, induced PBMCs
      harvested at days 2 and 4 of culture. A sensitive real-time PCR with a DNA
      equivalent of 3*10(5) cells per reaction was run in duplicate for all samples
      along with a quantitative HHV-8 DNA standard ranging from 1.6 to 200 copies.
      RESULTS: For all 164 donors, HHV-8 genomes were not detected in the DNA
      equivalent of 3-6*10(5) of PBMCs and induced/cultured PBMCs with a real-time PCR
      assay (95% CI: 0-3.5/164). HHV-8 DNA was not detected from DNA equivalent of 1.5
      (0.5-5.6)*10(5) CD19+ B cells from 139/164 donors. HHV-8 antibodies were detected
      in 7 of the 164 donors (4.3%). CONCLUSIONS: HHV-8 genomes were not detected from
      PBMCs, induced/cultured PBMCs and CD19+ B cells from 164 blood donors. The level
      of detectable HHV-8 genomes in blood donors seems to be extremely low, if they
      exist.

PMID- 20825599
TI  - Distribution of Diego blood group alleles and identification of four novel
      mutations on exon 19 of SLC4A1 gene in the Chinese Han population by polymerase
      chain reaction sequence-based typing.
AB  - BACKGROUND: The Diego blood group system plays an important role in transfusion
      medicine. Genotyping of DI1 and DI2 alleles is helpful for the investigation into
      haemolytic disease of the newborn (HDN) and for the development of rare blood
      group databases. Here, we set up a polymerase chain reaction sequence-based
      typing (PCR-SBT) method for genotyping of Diego blood group alleles. STUDY DESIGN
      AND METHODS: Specific primers for exon 19 of the solute carrier family 4, anion
      exchanger, member1 (SLC4A1) gene were designed, and our PCR-SBT method was
      established and optimized for Diego genotyping. A total of 1053 samples from the
      Chinese Han population and the family members of a rare proband with DI1/DI1
      genotype were investigated by the PCR-SBT method. An allele-specific primer PCR
      (PCR-ASP) was used to verify the reliability of the PCR-SBT method. RESULTS: The
      frequencies of DI1 and DI2 alleles in the Chinese Han population were 0.0247 and
      0.9753, respectively. Six new single nucleotide polymorphisms (SNPs) were found
      in the sequenced regions of the SLC4A1 gene, and four novel SNPs located in the
      exon 19, in which one SNP could cause an amino acid alteration of Ala858Ser on
      erythrocyte anion exchanger protein 1. The genotypes for Diego blood group were
      identical among 41 selected samples with PCR-ASP and PCR-SBT. CONCLUSION: The PCR
      SBT method can be used in Diego genotyping as a substitute of serological
      technique when the antisera is lacking and was suitable for screening large
      numbers of donors in rare blood group databases.

PMID- 20825600
TI  - The ethics of wasting the donor's gift of buffy coat.

PMID- 20825601
TI  - Central apnoeas in infants with bronchiolitis admitted to the paediatric
      intensive care unit.
AB  - AIM: To further characterize apnoea(s) complicating bronchiolitis because of
      respiratory syncytial virus (RSV), to describe the incidence of this complication
      and identify possible risk factors for apnoea(s) and its development. METHODS:
      The files of infants admitted to the paediatric intensive care unit (PICU) for
      RSV bronchiolitis during three bronchiolitis seasons (2004-2007) were reviewed
      for demographic, clinical and laboratory parameters. Parameters were compared
      between patients with and without apnoeas. RESULTS: Seventy-nine patients met the
      study criteria: 43 were admitted to the PICU for central apnoeas and the
      remainder for respiratory distress or failure. The percentage of infants admitted
      for apnoea increased during the study period (28.6 to 77.1%, p = 0.004). The
      overall prevalence of apnoea in this population was 4.3%. Possible risk factors
      for apnoea(s) were younger age (1.3 vs. 4.3 months, p = 0.002), lower admission
      weight (3.3 vs. 5 kg, p < 0.001), lower gestational age (35.8 vs. 37.8 weeks, p =
      0.01), admission from the emergency room (50% vs. 9.1%, p < 0.001) and lack of
      hyperthermia (p < 0.001). Respiratory acidosis was found to be a protective
      factor on logistic regression analysis. CONCLUSION: The prevalence of apnoea in
      infants admitted to the PICU for RSV bronchiolitis in our centre may be
      increasing. Preterm, younger infants with no fever are at relatively high risk of
      apnoea at presentation, while older infants with fever are at lower risk.

PMID- 20825602
TI  - Mortality in out-of-hospital premature births.
AB  - AIM: To determine whether the mortality for out-of-hospital (OOH) premature
      births was higher than for in-hospital premature births and identify additional
      risk factors. PATIENTS AND METHODS: A historical cohort study of a consecutive
      series of live-born, OOH, births of 24-35 weeks gestation cared for by two
      Transport Teams working in and around Paris, France 1994-2005. Matching with in
      hospital births was according to gestational age, antenatal steroid use, the mode
      of delivery and nearest year of birth. RESULTS: Eighty-five OOH premature births
      were identified, of whom 83 met inclusion criteria, and 132 matching in-hospital
      premature births were selected. There was 18% mortality in the OOH group compared
      with 8% for the in-hospital group [p = 0.04, OR 2.9, (CI 95% 1.0-8.4)]. Variables
      significantly associated (p < 0.05) with the OOH birth were HIV infection, lower
      maternal age and endo-tracheal intubation, lack of medical follow-up during
      pregnancy, low temperature and low birth weight. CONCLUSIONS: Mortality was more
      than twice as high in out-of-hospital deliveries than for in-hospital matched
      controls. Hypothermia was an important associated risk factor. Measures such as
      oxygen administration to maintain an appropriate saturation for gestational age,
      the provision of polyethylene plastic wraps and skin-to-skin contact are
      recommended.

PMID- 20825603
TI  - Motor development curve from 0 to 12 months in infants born preterm.
AB  - AIM: To trace a reference curve for motor development from birth up to 12 months
      of corrected chronological age in infants born preterm and low birth weight.
      METHODS: This is a cross-sectional study with a sample of 308 preterm infants
      (53% boys) weighing < 2500 g at birth. The Alberta Infant Motor Scale (AIMS) was
      used for motor development assessment. RESULTS: Comparing the motor performance
      of preterm infants with infants from a standardized sample on the AIMS, it was
      found that, except for the age group of the newborn, preterm infants showed lower
      motor development scores in comparison with the AIMS normative sample in all age
      groups between 1 and 12 months. The curve of motor development showed a
      continuous increase in the number of motor skills of preterm infants during their
      first 12 months of age. However, the average of motor acquisitions of preterm
      infants showed a nonlinear pattern with a standard indicator of stabilization
      between 8 and 10 months of age. CONCLUSION: Preterm infants, 1-12 months of age,
      showed motor development AIMS scores lower than the standards established in the
      normative sample. The findings may contribute as norm-reference for assessing the
      motor development of preterm infants in follow-up programmes in developing
      countries.

PMID- 20825604
TI  - Prevention of retinopathy of prematurity in preterm infants through changes in
      clinical practice and SpO2technology.
AB  - AIM: To identify whether pulse oximetry technology is associated with decreased
      retinopathy of prematurity (ROP) and laser treatment. METHODS: Inborn infants
      <1250 g who had eye exams were compared at two centres in three periods. In
      Period 1, SpO2 target was >=93% and pulse oximetry technology was the same in
      both Centres. In Period 2, guidelines for SpO2 88-93% were implemented at both
      centres and Centre B changed to oximeters with signal extraction technology
      (SET((r))) while Centre A did not, but did so in Period 3. One ophthalmology
      department performed eye exams using international criteria. RESULTS: In 571
      newborns <1250 g, birth weight and gestational age were similar in the different
      periods and centres. At Centre A, severe ROP and need for laser remained the same
      in Periods 1 and 2, decreasing in Period 3-6% and 3%, respectively. At Centre B,
      severe ROP decreased from 12% (Period 1) to 5% (Period 2) and need for laser
      decreased from 5% to 3%, remaining low in Period 3. CONCLUSION: In a large group
      of inborn infants <1250 g, a change in clinical practice in combination with
      pulse oximetry with Masimo SET, but not without it, led to significant reduction
      in severe ROP and need for laser therapy. Pulse oximetry selection is important
      in managing critically ill infants.

PMID- 20825605
TI  - Corporal punishment and child maltreatment in New Zealand.
AB  - On 2 May, 2007, the New Zealand Parliament passed a law repealing Section 59 of
      the Crimes Act. In so doing, New Zealand became the first English-speaking nation
      in the world to make corporal punishment of a child illegal. The passage of this
      legislation was surrounded by intense and persistent public debate, and
      supporters of corporal punishment continue to advocate against the law change to
      the present day. In Sweden, where the first stage of similar repeal took place in
      1957, it may be difficult for many to understand the strength of the public
      opposition to this change in New Zealand. This article will present a viewpoint
      on the evolution of the debate in New Zealand, review the wider context of child
      maltreatment and family violence in New Zealand and summarize a range of attempts
      to prevent or intervene effectively in the cycle of dysfunction. CONCLUSION:
      Child maltreatment and family violence are public health issues of great
      importance, and a stain on all societies. While corporal punishment may be a
      significant contributing factor, there is no single 'solution'. Change must occur
      on multiple levels (political, economic, cultural, familial and professional)
      before the tide will turn.

PMID- 20825606
TI  - The effect of day care attendance on infant and toddler's growth.
AB  - AIM: We aimed to study the association between day care attendance and changes in
      the height, weight and weight/height ratio over a 6-month period. METHODS: Data
      were retrieved from three maternal and child health care centres. Parents were
      asked to fill a short questionnaire regarding the infant/toddler life style, the
      day care facilities and the family demographic information. RESULTS: One hundred
      and seventy infants participated in the study. The research group consisted of 85
      infants that had placed in day care centre prior to the age of 18 months. The
      control group consisted of 85 infants who had placed in day care at a later age.
      The research group had significantly shorter stature 3 months after day care
      enrolment (mean height percentiles of 56.9 versus 66.3, respectively, p =
      0.024,). This trend was more pronounced after 6 months (mean height percentiles
      of 52.3 versus 63.7, p = 0.022). We could not, however, demonstrate a concomitant
      significant deceleration in weight or weight/height percentiles. CONCLUSIONS: The
      explanation for this rather dramatic finding remains speculative. Possible
      mechanisms are stress-related growth hormone suppression. Our findings reinforce
      the importance of monitoring infant/toddler weight and height growth velocities,
      especially when he/she is introduced to day care.

PMID- 20825608
TI  - Immunisation rates of children with cystic fibrosis using the Australian
      Childhood Immunisation Register.
AB  - AIM: The Australian Immunisation Handbook (ninth edition) recommends children
      with cystic fibrosis (CF) receive routine scheduled immunisations plus annual
      influenza vaccine and an additional pneumococcal vaccine at both 12 months and 4
      5 years. Adherence with these recommendations is unknown. This study aimed to
      determine the immunisation status of children with CF attending the Royal
      Children's Hospital (RCH), Melbourne. METHODS: A retrospective audit of children
      with CF aged 6 months to 7 years (at 1 January 2008) was performed on the RCH CF
      outpatient clinic database. The Australian Childhood Immunisation Register (ACIR)
      and RCH Immunisation Service records were used to determine immunisation status.
      RESULTS: Eighty-nine children with CF were identified, 52 (58%) were male, with
      median age of 3.6 years. Eighty-two of 89 children (92%) were up to date with
      routine immunisations. According to the ACIR, of the 89 children sampled, 24
      (27%) were given influenza vaccine in accordance with recommendations in 2007.
      Eighty children were older than 12 months of age at 1 January 2008 and 17 (21%)
      of these children had received the additional pneumococcal vaccine at 12 months.
      Thirty-eight children were older than 4 years of age at 1 January 2008 and 6
      (16%) received the recommended 23vPPV booster. CONCLUSION: Most children with CF
      received their routine childhood immunisations but not the additional recommended
      immunisations. This highlights the potential value of the ACIR to accurately
      record all vaccines administered and for ACIR reminder letters to include the
      additional vaccines for children in special-risk groups.

PMID- 20825609
TI  - Driveway runover, the influence of the built environment: a case control study.
AB  - AIM: Driveway runover injuries are a frequent cause of paediatric mortality and
      morbidity throughout the world. Driveway runovers occur as a result of an
      interaction between human factors (child and driver), vehicle factors
      (visibility) and environmental factors (driveway design and surroundings). This
      study investigates the environmental factors involved in these injuries. METHODS:
      Case control study, Auckland, New Zealand. Cases were the properties where
      paediatric driveway injuries (age < 7 years) requiring hospital admission had
      occurred. Control properties were selected from the addresses of children
      presenting to the emergency department with a non-driveway injury. Blinded
      assessment of properties was completed using satellite images, site visits and
      searches of council records. RESULTS: Analysis was completed on 88 case
      properties and 181 controls. The risk of injury was increased by a driveway
      length greater than 12m (OR = 1.8, 95%CI = 1.1-3.0), exiting the driveway onto a
      local road (OR = 5.5, 95% CI = 2.7-11.2) and the driveway exiting onto a cul-de
      sac (OR = 2.3, 95%CI = 1.4-3.9). The risk of driveway injury was increased when
      more parking areas were on the property (accessed from the driveway) (OR = 3.0,
      95%CI = 1.6-5.4) and when the driveway runs along the property boundary (OR =
      2.9, 95%CI = 1.6-5.2). A separate pedestrian pathway on the property was
      associated with a lower risk of injury (OR = 0.4, 95%CI= 0.2-0.9). CONCLUSIONS: A
      number of built environment features contribute to driveway runover injuries.
      This information should be used by those within the design and building community
      to reduce the risk of further driveway runover injury.

PMID- 20825610
TI  - Impact of introducing binasal continuous positive airway pressure for acute
      respiratory distress in newborns during retrieval: Experience from Western
      Australia.
AB  - AIM: We aimed to review the impact of introducing binasal continuous positive
      airway pressure (CPAP) for acute respiratory distress in newborns >=32 weeks
      gestation during retrieval in Western Australia. METHODS: Retrospective review of
      newborns >=32 weeks gestation with acute respiratory distress, transported by the
      Western Australian Neonatal Transport Service between February 2002 and December
      2004. RESULTS: Respiratory management of 369 newborns was examined. CPAP use
      increased significantly during the study period from 33% in 2002 to 59% in 2004.
      Overall, endotracheal tube (ETT) ventilation was required in 108 (29%), nasal
      CPAP in 166 (45%) and cot oxygen in 95 (26%) patients. Twenty-two (13%) newborns
      in the CPAP group subsequently required ETT ventilation within 24 h: these babies
      had higher initial oxygen requirements than those successfully transported on
      CPAP alone. There was no significant morbidity or mortality in patients retrieved
      on CPAP. CONCLUSION: CPAP was increasingly utilised as an alternative to ETT
      ventilation for the management of most cases of less severe acute respiratory
      distress in near-term neonates on retrieval. This review demonstrated that
      newborns requiring more than 45-50% oxygen at the time of retrieval were more
      likely to require intubation at a later time, and hence may benefit from
      intubation at the time of retrieval. A prospective randomised trial would assist
      in ascertaining the true benefit of CPAP during retrieval in the newborn period.

PMID- 20825611
TI  - Frequency of respiratory deterioration after immunisation in preterm infants.
AB  - AIM: To determine the relationship between the initiation of respiratory support
      and the first routine immunisation of neonates at 2 months of age during primary
      hospitalisation. METHODS: An historical cohort study design was used to study the
      neonatal factors associated with the initiation of respiratory support within 7
      days of immunisation in a cohort of 7629 preterm and term infants admitted to the
      Neonatal Unit of the Royal Women's Hospital between 2001 and 2008. RESULTS: The
      411 infants who received their first immunisations in hospital were both very
      preterm and of extremely low birth weight (ELBW, below 1000 g). Twenty-two
      infants experienced post-immunisation apnoea of sufficient severity to warrant
      the initiation of either intermittent positive pressure ventilation (two cases)
      or continuous positive airway pressure (20 cases). Infants exhibiting a
      respiratory deterioration following immunisation had a higher incidence of
      previous septicaemia (Odds ratio 2.5, 95% confidence interval 1.0, 6.1; P = 0.04)
      and received CPAP for a longer period prior to vaccination (P = 0.03).
      CONCLUSION: Apnoea following immunisation may be an aetiological factor in the
      requirement of respiratory support in a small number of preterm, ELBW infants
      particularly those with significant lung disease and those who have previously
      experienced septicaemia.

PMID- 20825612
TI  - Systematic review of systemic antibiotic treatment for children with chronic and
      sub-acute pyogenic osteomyelitis.
AB  - BACKGROUND: There is a lack of consensus on the most appropriate antibiotics to
      treat children with chronic or sub-acute pyogenic bacterial osteomyelitis and on
      the optimal duration of antibiotic therapy. AIM: To review the published evidence
      on the duration of antibiotic therapy and outcomes in children with chronic and
      sub-acute pyogenic bacterial osteomyelitis. METHODS: Systematic review of the
      literature. RESULTS: We found no randomised controlled trials comparing different
      antibiotic regimens or comparing duration of antibiotic treatment for chronic or
      sub-acute osteomyelitis in children. We found 14 observational case series
      published between 1973 and 2008. Most children with chronic osteomyelitis
      received 4-6 weeks of parenteral antibiotics followed by oral antibiotics to a
      total duration of 3-6 months. Small observational studies suggest that a shorter
      duration of parenteral and oral antibiotics may be equally effective. CONCLUSION:
      There is no high level evidence on the optimal duration of parenteral and oral
      antibiotics for children with chronic or sub-acute osteomyelitis. A large
      randomised controlled trial is needed comparing short course parenteral and oral
      antibiotics with longer antibiotic duration.

PMID- 20825613
TI  - Pet ownership and adolescent health: cross-sectional population study.
AB  - OBJECTIVE: To determine whether adolescent health and well-being are associated
      with having a pet in the household (any pet, or specifically dogs, cats or
      horses/ponies) or average daily time spent caring for/playing with pet(s).
      METHODS: Design, setting and participants--Cross-sectional data from the third
      wave of the Health of Young Victorians Study (HOYVS), a school-based population
      study in Victoria, Australia. Predictors--Adolescent-reported pet ownership and
      average daily time spent caring for/playing with pet(s). Outcomes--Self-reported
      quality of life (KIDSCREEN); average 4-day daily physical activity level from a
      computerised diary; parent-proxy and self-reported physical and psychosocial
      health status (PedsQL); measured BMI status (not overweight, overweight, obese)
      and blood pressure. Statistical Analysis--Regression methods, adjusted for socio
      demographic factors, and non-parametric methods. RESULTS: Household pet data were
      available for 928 adolescents (466 boys; mean age of 15.9 (SD 1.2) years). Most
      adolescents (88.7%) reported having a pet in their household. Of these, 75.1%
      reported no activity involving pets over the surveyed days. It appeared that
      neither owning a pet nor time spent caring for/playing with a pet was related,
      positively or negatively, to adolescent health or well-being. CONCLUSIONS:
      Despite high rates of pet ownership, adolescents had little interaction with
      pets. It appears that owning a pet and time spent caring for/playing with a pet
      was not clearly associated with adolescents' health or well-being.

PMID- 20825614
TI  - Paediatric frequent attenders at emergency departments: a linked-data population
      study.
AB  - AIM: To characterise the phenomena of paediatric frequent attenders (FAs) to
      emergency departments (EDs) in Perth. METHODS: A linked data population study of
      all children (<15 years) attending Perth hospital EDs between 1 July 2000 and 31
      December 2006. FAs attending five or more times annually were assessed for
      demographic characteristics, mode of arrival, urgency, clinical conditions and
      disposition by frequency of attendance. RESULTS: Over 6.5 years, 229, 883
      children contributed to 378, 068 annualised chains of events (mean 1.5). Most
      children (98.2%) attended EDs less than five times a year. The more frequently
      children attended, the more likely they were to be male, younger, self-referred,
      have respiratory or infectious disorders, and to arrive by ambulance.
      Characteristics of those attending 0-4 (n= 371 171) and 5-9 (n= 6405) times per
      year were broadly similar, while those attending 10-19 times per year (n= 461)
      were more urgent, had a higher frequency of respiratory disease and higher
      admission rates (all P < 0.001). Those attending more than 20 times a year (n=
      31) had serious chronic illness. CONCLUSIONS: Frequent attenders of 5-9 times a
      year may be no sicker or more in need of hospital services than those who attend
      less frequently. The preponderance of respiratory and infectious disorders across
      all FA groups suggests these could be the focus of further research. We advocate
      a holistic approach to take into account parental expectations, and a systems
      approach to change ED attendance behaviour.

PMID- 20825615
TI  - Effect of the dose volume of perfluorocarbon when starting partial liquid
      ventilation.
AB  - OBJECTIVE: Very preterm neonates are prone to brain injury if cerebral blood flow
      fluctuates. Partial liquid ventilation (PLV) may benefit any lung disease but
      giving 30 mL/kg of perfluorocarbon when starting PLV increases cortical cerebral
      blood flow velocity. We aimed to determine if varying the initial dose of
      perfluorocarbon alters the effect on cerebral blood flow velocity when starting
      PLV. METHODS: In this randomised, controlled trial with historical comparison 24
      preterm lambs received one of three loading doses of intratracheal
      perfluorocarbon liquid over 20 min when starting PLV: 20, 30 or 40 mL/kg. Data on
      respiratory mechanics, haemodynamics and cerebral blood flow velocity, measured
      with laser Doppler, were collected continuously for 30 min from the start of
      dosing. RESULTS: Cortical cerebral blood flow velocity increased over time in all
      three groups (two-way ANOVA, P= 0.007). There was no difference between groups
      (two-way ANOVA, P= 0.26). There was no difference between groups in cortical
      cerebral blood flow velocity variability (P= 0.68), blood pressure (P= 0.96) or
      heart rate (P= 0.46). The was no statistically significant difference in PaCO(2)
      between groups measured at baseline and at 30 min after starting PLV (P= 0.51).
      CONCLUSIONS:   Cortical cerebral blood flow velocity and its variability are not
      affected by varying doses of tracheal perfluorocarbon (20, 30 or 40 mL/kg) at the
      start of PLV in preterm lambs.

PMID- 20825616
TI  - Correlation between unconjugated bilirubin and total cholesterol in the sera of 1
      month-old infants.
AB  - AIM: To investigate why breastfed infants are more likely to have prolonged
      jaundice than formula-fed infants. METHODS: Serum unconjugated bilirubin (UCB),
      total cholesterol (TC) and triglyceride (TG) were measured for 102 infants of 1
      month. Enrolled infants were 42 breastfed, 40 mixed-fed and 20 bottle-fed
      infants. Statistic analyses for relationship among UCB, TC, TG, perinatal factors
      and post-natal factors were performed for these infants. RESULTS: In correlation
      analyses UCB was correlated with peak transcutaneous bilirubin value in neonatal
      period (TcBn) (r = 0.612, P < 0.0001) and with TC (r = 0.383, P < 0.0001). When
      analyses of covariance (ANCOVA) for UCB were performed using TcBn as the
      covariate, the results indicated that there was neither significant main nor
      interaction effect of feeding method on UCB, and that main and interaction
      effects of TC on UCB were significant when TC was categorised into two groups
      (<=150 mg/dL and >150 mg/dL). CONCLUSIONS: It is suggested that both neonatal
      hyperbilirubinemia and subsequent higher plasma TC are associated factors for
      prolonged jaundice.

PMID- 20825617
TI  - Network meta-analysis with competing risk outcomes.
AB  - BACKGROUND: Cost-effectiveness analysis often requires information on the
      effectiveness of interventions on multiple outcomes, and commonly these take the
      form of competing risks. Nevertheless, methods for synthesis of randomized
      controlled trials with competing risk outcomes are limited. OBJECTIVE: The aim of
      this study was to develop and illustrate flexible evidence synthesis methods for
      trials reporting competing risk results, which allow for studies with different
      follow-up times, and that take account of the statistical dependencies between
      outcomes, regardless of the number of outcomes and treatments. METHODS: We
      propose a competing risk meta-analysis based on hazards, rather than
      probabilities, estimated in a Bayesian Markov chain Monte Carlo (MCMC) framework
      using WinBUGS software. Our approach builds on existing work on mixed treatment
      comparison (network) meta-analysis, which can be applied to any number of
      treatments, and any number of competing outcomes, and to data sets with varying
      follow-up times. We show how a fixed effect model can be estimated, and two
      random treatment effect models with alternative structures for between-trial
      variation. We suggest methods for choosing between these alternative models.
      RESULTS: We illustrate the methods by applying them to a data set involving 17
      trials comparing nine antipsychotic treatments for schizophrenia including
      placebo, on three competing outcomes: relapse, discontinuation because of
      intolerable side effects, and discontinuation for other reasons. CONCLUSIONS:
      Bayesian MCMC provides a flexible framework for synthesis of competing risk
      outcomes with multiple treatments, particularly suitable for embedding within
      probabilistic cost-effectiveness analysis.

PMID- 20825618
TI  - Discrete choice modeling for the quantification of health states: the case of the
      EQ-5D.
AB  - OBJECTIVES: Probabilistic models have been developed to establish the relative
      merit of subjective phenomena by means of specific judgmental tasks involving
      discrete choices (DCs). The attractiveness of these DC models is that they are
      embedded in a strong theoretical measurement framework and are based on
      relatively simple judgmental tasks. The aim of our study was to determine whether
      the values derived from a DC experiment are comparable to those obtained using
      other valuation techniques, in particular the time trade-off (TTO). METHODS: Two
      hundred nine students completed several tasks in which we collected DC, rank,
      visual analog scale, and TTO responses. DC data were also collected in a general
      population sample (N=444). The DC experiment was designed using a Bayesian
      approach, and involved 60 choices between two health states and a comparison of
      all health states to being dead. The DC data were analyzed using a conditional
      logit and a rank-ordered logit model, relying, respectively, on TTO values and
      the value for being dead to anchor the DC-derived values to the 0 to 1 quality
      adjusted life-year (QALY) scale. RESULTS: Although modeled DC data broadly
      replicated the pattern found in TTO responses, the DC consistently produced
      higher values. The two methods for anchoring DC-derived values on the QALY scale
      produced similar results. CONCLUSIONS: On the basis of the high level of
      comparability between DC-derived values and TTO values, future valuation studies
      based on a combination of these two techniques may be considered. The results
      further suggest that DC can potentially be used as a substitute for TTO.

PMID- 20825619
TI  - Cost-utility analysis of tenofovir disoproxil fumarate in the treatment of
      chronic hepatitis B.
AB  - OBJECTIVE: The aim of this study was to assess the cost-effectiveness of
      tenofovir disoproxil fumarate (TDF) in the treatment of chronic hepatitis B (CHB)
      versus alternative nucleos(t)ides from a UK National Health Service (NHS)
      perspective. METHODS: A Markov model was used to calculate costs and benefits of
      nucleos(t)ide strategies in hepatitis B e antigen (HBeAg)-positive and HBeAg
      negative patients with hepatitis B virus mono-infection and compensated liver
      disease. The model included 18 disease states representing CHB progression.
      Quality-of-life data and costs for severe disease states were based on published
      studies, while monitoring costs for other disease states were based on expert
      opinion. Transition probabilities for movements between states were based on a
      meta-analysis, clinical trials, and natural history studies. RESULTS: First-line
      TDF generated the highest net benefits of all 211 nucleos(t)ide strategies
      evaluated at a threshold of L 20,000 per quality-adjusted life-year (QALY)
      gained. First-line TDF cost L 19,084/QALY gained compared with giving lamivudine
      (LAM) first-line and switching to TDF when LAM resistance occurs. First-line TDF
      was also more effective and less costly than first-line entecavir (ETV), and
      showed extended dominance over first-line adefovir and strategies reserving
      adefovir, ETV, or combination therapy until after LAM resistance develops. For
      patients who have developed LAM resistance, TDF was also the most cost-effective
      treatment, generating greater net benefits than any other second-line strategy.
      CONCLUSIONS: First-line TDF is the most cost-effective treatment for patients
      with CHB at a L 20,000 to L 30,000/QALY ceiling ratio, costing L 19,084/QALY
      gained compared with the next best alternative.

PMID- 20825620
TI  - Willingness to pay for a quality-adjusted life-year: the individual perspective.
AB  - OBJECTIVE: The aim of this study was to elicit the individual willingness to pay
      (WTP) for a quality-adjusted life-year (QALY). METHODS: In a Web-based
      questionnaire containing contingent valuation exercises, respondents valued
      health changes in five scenarios. In each scenario, the respondents first valued
      two health states on a visual analog scale (VAS) and expressed their WTP for
      avoiding a decline in health from the better health state to the worse, using a
      payment scale followed by a bounded open contingent valuation question. ANALYSIS:
      WTP per QALY was calculated for QALY gains calculated using VAS valuations, as
      well as the Dutch EQ-5D tariffs, the two steps in the WTP estimations and each
      scenario. Heterogeneity in WTP per QALY ratios was examined from the perspective
      of: 1) household income; and 2) the level of certainty in WTP indicated by
      respondents. Theoretical validity was analyzed using clustered multivariate
      regressions. RESULTS: A total of 1091 respondents, representative of the Dutch
      population, participated in the survey. Mean WTP per QALY was ? 12,900 based on
      VAS valuations, and ? 24,500 based on the Dutch EuroQoL tariffs. WTP per QALY was
      strongly associated with income, varying from ? 5000 in the lowest to ? 75,400 in
      the highest income group. Respondents indicating higher certainty exhibited
      marginally higher WTP. Regression analyses confirmed expected relations between
      WTP per QALY, income, and other personal characteristics. CONCLUSION:  
      Individual WTP per QALY values elicited in this study are similar to those found
      in comparable studies. The use of individual valuations in social decision-making
      deserves attention, however.

PMID- 20825621
TI  - Predicting time trade-off health state valuations of adolescents in four Pacific
      countries using the Assessment of Quality-of-Life (AQoL-6D) instrument.
AB  - OBJECTIVES: Pacific Obesity Prevention in Communities (OPIC) is a community-based
      intervention project targeting adolescent obesity in Australia, New Zealand,
      Fiji, and Tonga. The Assessment of Quality of Life Mark 2 (AQoL-6D) instrument
      was completed by 15,481 adolescents to obtain a description of the quality of
      life associated with adolescent overweight and obesity, and a corresponding
      utility score for use in a cost-utility analysis of the interventions. This
      article describes the recalibration of this utility instrument for adolescents in
      each country. METHODS: The recalibration was based on country-specific time trade
      off (TTO) data for 30 multiattribute health states constructed from the AQoL-6D
      descriptive system. Senior secondary students, in a classroom setting, responded
      to 10 health state scenarios each. These TTO interviews were conducted for 24
      groups, comprising 279 students in the four countries resulting in 2790 completed
      TTO scores. The TTO scores were econometrically transformed by regressing the TTO
      scores upon predicted scores from the AQoL-6D to produce country-specific
      algorithms. The latter incorporated country-specific "corrections" to the
      Australian adult utility weights in the original AQoL. RESULTS: This article
      reports two methodological elements not previously reported. The first is the
      econometric modification of an extant multi-attribute utility instrument to
      accommodate cultural and other group-specific differences in preferences. The
      second is the use of the TTO technique with adolescents in a classroom group
      setting. Significant differences in utility scores were found between the four
      countries. CONCLUSION: Statistical results indicate that the AQoL-6D can be
      validly used in the economic evaluation of both the OPIC interventions and other
      adolescent programs.

PMID- 20825622
TI  - Is longer waiting time for total knee replacement associated with health outcomes
      and medication costs? Randomized clinical trial.
AB  - BACKGROUND: The aim of this prospective randomized study was to evaluate the
      effect of waiting time (WT) on health-related quality of life (HRQoL), knee pain
      and physical function, and the use and costs of medication of patients awaiting
      total knee replacement. METHODS: When placed on the waiting list, 438 patients
      were randomized into a short waiting time (SWT <= 3 months) or a nonfixed waiting
      time (NFWT > 3 months) group. HRQoL was measured by the 15D, and pain and
      physical function by modified Knee Society Clinical Rating System at baseline,
      admission, and 3 and 12 months postoperatively. The costs of medication due to
      osteoarthritis were calculated at the same measurement points. All analyses were
      performed using the intention-to-treat principle. RESULTS: The mean WT was 94 and
      239 days in the SWT and NFWT groups, respectively. Apart from higher weekly cost
      of medication in the SWT group at admission and better HRQoL in the NFWT group 1
      year postoperatively, there were no statistically significant differences between
      the groups in other outcomes during the follow-up. CONCLUSION: Those in the SWT
      group had higher weekly costs of medication at admission, and reached better
      HRQoL 3 months earlier than those in the NFWT group, but the latter had better
      HRQoL after operation. Otherwise, the length of WT was not associated with
      different health and HRQoL outcomes in the groups.

PMID- 20825623
TI  - Historical lifetimes of drugs in England: application to value of information and
      cost-effectiveness analyses.
AB  - OBJECTIVES: The expected lifetime of a health technology is a critical parameter
      in value of information analysis and in two methodologies for cost-effectiveness
      analysis which have recently been suggested. The first method allows for the
      possibility that a superior technology will become available in the future. The
      second advocates modeling both the prevalent and all future incident patient
      cohorts. Unfortunately, for value of information analysis, the period of time
      over which information about the decision problem would be useful is very
      uncertain, and existing estimates are seemingly arbitrary. Furthermore, there is
      very little literature on the historical lifetimes of technologies. Here, I
      quantify and analyze the historical lifetimes of drugs in England. I then apply
      this information to inform the value of further research and the cost
      effectiveness of health technologies. METHODS: A Weibull regression model was
      fitted to the historical drug lifetimes of 455 drugs. These represented all
      British National Formulary drugs in England which were launched from 1981 to
      2007, and which did not have very low sales volumes. RESULTS: The mean drug
      lifetime was 57 years (95% confidence interval 39-79 years), and the median was
      46 years (35-60 years). Drugs with low sales volumes tended to have shorter
      lifetimes. Under certain assumptions, the ratio of population level to per-year
      expected value of information is 21. Drug lifetimes are used to parameterize the
      two models of cost-effectiveness. CONCLUSIONS: The distribution function of the
      historical lifetimes of drugs can inform suitable time horizons for: 1) value of
      information; and 2) cost-effectiveness analyses related to drugs.

PMID- 20825624
TI  - Mixed treatment comparison meta-analysis evaluating the relative efficacy of
      nucleos(t)ides for treatment of nucleos(t)ide-naive patients with chronic
      hepatitis B.
AB  - BACKGROUND/AIMS: Five nucleoside/nucleotide treatments are now available for
      chronic hepatitis B (CHB). This meta-analysis aimed to assess the relative
      efficacy of adefovir, entecavir, lamivudine, telbivudine, tenofovir disoproxil
      fumarate (TDF), and nucleos(t)ide combinations in the treatment of CHB. METHODS:
      A systematic review of MEDLINE and the Cochrane library was conducted to identify
      all studies evaluating these nucleos(t)ides in adults with CHB. Randomized
      controlled trials were included in the meta-analysis if they reported the
      proportion of patients with undetectable hepatitis B virus (HBV) DNA or hepatitis
      B e antigen (HBeAg) loss/seroconversion at 1 year. Bayesian mixed treatment
      comparison meta-analyses were conducted in WinBUGS to assess relative efficacy.
      RESULTS: A random-effects meta-analysis of trials on treatment-naive patients
      with HBeAg-positive CHB demonstrated that 94% of patients will achieve HBV DNA <
      300 copies/ml after 1 year with TDF, compared with 73% for entecavir, 50% for
      adefovir, and 38% for lamivudine. There was a 97.7% probability that TDF enabled
      a greater proportion of patients to achieve HBV DNA < 300 copies/ml at 1 year
      than all other treatments considered in the analysis. TDF was significantly
      superior to all nucleos(t)ides for this outcome at the 0.05 level. There were no
      statistically significant differences between nucleos(t)ides in HBeAg
      seroconversion at 1 year, based on a fixed-effects meta-analysis in the same
      population. More trials on HBeAg-negative and drug-resistant patients are
      required to facilitate meta-analyses for these subgroups. CONCLUSIONS: In
      nucleos(t)ide-naive patients with HBeAg-positive CHB, TDF is associated with the
      highest probability of achieving undetectable HBV DNA at 1 year of all
      nucleos(t)ides considered.

PMID- 20825625
TI  - Medical services utilization and expenditure of obesity-related disorders in
      Taiwanese adults.
AB  - OBJECTIVES: To evaluate medical service utilization and medical expenditure
      associated with obesity-related diseases among different weight status subjects
      in Taiwan. METHODS: A cross-sectional survey based on the National Health
      Interview Survey performed in 2001. Subjects greater than 20 years old who lived
      in Taiwan, as corroborated by National Health Insurance (NHI), during 2001, were
      included. Overall, the data set included 15,461 subjects with age of 20-85 years
      old. After excluding those subjects with incomplete or missing data or who
      refused to link their data with the NHI data, 12,283 subjects were used for
      analyses. RESULTS: In general, obesity-related disorders, such as hypertension,
      diabetes mellitus (DM), and cardiovascular diseases have increasing prevalence
      with greater body mass index (BMI; P<0.001). Obese subjects (BMI?27kg/m(2) ) had
      the highest prevalence of hypertension (31.9%), after DM (26.9%). After adjusting
      for age, smoking, drinking and obesity-related disorders, it was found that
      medical utilization in outpatient increases from 1.33 to 4.04 visits/year
      (P<0.001) and in-hospital increases from 0.05 to 0.07 admissions/year (P>0.05)
      with higher BMI. Average outpatient expenditure (including physician fee,
      laboratory test and drug costs) per year is NT$1201, 1857, 3960, and 5118 (at an
      exchange rate of NT$32 to US$1) for underweight, normal, overweight, and obese
      subjects, respectively (P<0.001). CONCLUSIONS: Medical utilization and outpatient
      medical expenditure was found to increase with higher BMI status. However, there
      was a J-shaped (in female) or even negative (in male) relationship between BMI
      and in-hospital medical expenditures. Further studies are needed to resolve this
      major public health problem, even in a developing country such as Taiwan.

PMID- 20825626
TI  - Discrete event simulation: the preferred technique for health economic
      evaluations?
AB  - OBJECTIVES: To argue that discrete event simulation should be preferred to cohort
      Markov models for economic evaluations in health care. METHODS: The basis for the
      modeling techniques is reviewed. For many health-care decisions, existing data
      are insufficient to fully inform them, necessitating the use of modeling to
      estimate the consequences that are relevant to decision-makers. These models must
      reflect what is known about the problem at a level of detail sufficient to inform
      the questions. Oversimplification will result in estimates that are not only
      inaccurate, but potentially misleading. RESULTS: Markov cohort models, though
      currently popular, have so many limitations and inherent assumptions that they
      are inadequate to inform most health-care decisions. An event-based individual
      simulation offers an alternative much better suited to the problem. A properly
      designed discrete event simulation provides more accurate, relevant estimates
      without being computationally prohibitive. It does require more data and may be a
      challenge to convey transparently, but these are necessary trade-offs to provide
      meaningful and valid results. CONCLUSION: In our opinion, discrete event
      simulation should be the preferred technique for health economic evaluations
      today.

PMID- 20825627
TI  - The modeled lifetime cost-effectiveness of published adherence-improving
      interventions for antihypertensive and lipid-lowering medications.
AB  - OBJECTIVE:  We sought to compare the cost-effectiveness of different
      interventions that have been shown to improve adherence with antihypertensive and
      lipid-lowering therapy, by combining a burden of nonadherence model framework
      with literature-based data on adherence-improving interventions. METHODS:  
      MEDLINE was reviewed for studies that evaluated >=1 adherence intervention
      compared with a control, used an adherence measure other than self-report, and
      followed patients for >=6 months. Effectiveness was assessed as Relative
      Improvement, ratio of adherence with an intervention versus control. Costs,
      standardized to 12 months and adjusted to 2007 US$, and effectiveness estimates
      for each intervention were entered into a previously published model designed to
      measure the burden of nonadherence with antihypertensive and lipid-lowering
      medications, in a hypertensive population. Outputs included direct medical costs
      and incremental costs per quality-adjusted life-year (QALY) gained. RESULTS: 
      After screening, 23 eligible adherence-improving interventions were identified
      from 18 studies. Relative Improvement ranged from 1.13 to 3.60. After eliminating
      more costly/less effective interventions, two remained. Self-monitoring,
      reminders, and educational materials incurred total health-care costs of $17,520,
      and compared with no adherence intervention, had an incremental cost
      effectiveness ratio (ICER) of $4984 per QALY gained. Pharmacist/nurse management
      incurred total health-care costs of $17,896, and versus self-monitoring,
      reminders, and education had an ICER of $6358 per QALY gained. CONCLUSIONS:  Of
      published interventions shown to improve adherence, reminders and educational
      materials, and a pharmacist/nurse management program, appear to be cost-effective
      and should be considered before other interventions. Understanding relative cost
      effectiveness of adherence interventions may guide design and implementation of
      efficient adherence-improving programs.

PMID- 20825629
TI  - Spontaneous splenic rupture in Waldenstrom's macroglobulinemia: a case report.
AB  - INTRODUCTION: We report the case of a patient with Waldenstrom's
      macroglobulinemia complicated by spontaneous splenic rupture. CASE PRESENTATION:
      A 49-year-old Caucasian woman was referred to our emergency department by her
      general practitioner following a three-week history of malaise, night sweats, six
      kilograms of weight loss, intermittent nausea and vomiting, progressive upper
      abdominal pain and easy bruising. On the fourth day following her admission, she
      had a rapid clinical deterioration, with subsequent radiological investigations
      revealing a splenic rupture. Her morphology, biochemistry, flow cytometry and
      histology were strongly suggestive of Waldenstrom's macroglobulinemia.
      CONCLUSIONS: Spontaneous splenic rupture is not an expected complication of low
      grade lymphoplasmacytic lymphomas, such as Waldenstrom's macroglobulinemia. To
      the best of our knowledge, this is the only reported case of early spontaneous
      splenic rupture due to Waldenstrom's macroglobulinemia. Our case highlights that
      despite the typical disease course of low-grade hematological malignancies, signs
      and symptoms of imminent splenic rupture should be considered when formulating a
      clinical assessment.

PMID- 20825628
TI  - Ovarian steroid hormones: what's hot in the stem cell pool?
AB  - The vital role of ovarian hormones in the development of the normal breast
      foreshadowed their importance in mammary stem cell regulation. Two recent papers
      reveal that 17beta-estradiol and progesterone control the size and repopulating
      ability of the mammary stem cell compartment. This likely occurs via paracrine
      signaling from steroid receptor-positive luminal cells to steroid receptor
      negative stem cells. These findings illuminate roles for the female sex steroids
      in mobilizing the stem cell pool in the normal breast, and also provide a crucial
      link between the known hormonal risks of breast cancer and the potential stem
      cell origin of this disease.

PMID- 20825630
TI  - Palmaria palmata (Dulse) as an unusual maritime aetiology of hyperkalemia in a
      patient with chronic renal failure: a case report.
AB  - INTRODUCTION: Hyperkalemia is rare in individuals with normal renal function,
      regardless of dietary intake. This is due to the ability of the kidneys to adapt
      to increasing serum potassium concentrations. In patients with renal compromise,
      potassium homeostasis can become impaired. Palmaria palmata (dulse) is an edible
      seaweed known to be very rich in potassium. We report a case of hyperkalemia
      precipitated by the consumption of dulse by a patient with known renal disease.
      CASE PRESENTATION: A 66-year-old Caucasian woman with diabetes and chronic renal
      disease presented to our emergency department with nausea, vomiting, and
      worsening malaise, which had been present for less than a day. She had undergone
      electrocardiogram monitoring, which showed bradycardia, and periods of asystole.
      Our patient denied any other symptoms. Laboratory analysis revealed a serum
      potassium level of 8.6 mmol/L (normal range 3.5 to 4.9 mmol/L). Although our
      patient was taking some medications known to influence renal function, the only
      recent change that she could recount was that she had consumed approximately 200
      g of dulse within the preceding 24 hours. A diagnosis of hyperkalemia was made,
      and the patient was treated successfully, and discharged home in her pre-morbid
      state. CONCLUSION: To the best of our knowledge, this is the first published
      report of hyperkalemia due to dulse consumption. Dulse is high in potassium, with
      concentrations upwards of 34 times greater than that found in bananas. Caution
      should be taken in prescribing medications with potential adverse renal effects
      for patients with known renal impairment. In such instances, renal function
      should be monitored closely. Patients should be counseled to avoid dietary
      sources high in potassium, with particular attention paid to unusual geographical
      dietary variations.

PMID- 20825631
TI  - Duodenal gastrointestinal stromal tumor resembling a pancreatic neuroendocrine
      tumor in a patient with neurofibromatosis type I (von Recklinghausen's disease):
      a case report.
AB  - INTRODUCTION: Gastrointestinal stromal tumor is the most frequent nonepithelial
      tumor found in the gastrointestinal tract. One important clinical problem is that
      gastrointestinal stromal tumors, especially the extramural growth type, can be
      difficult to distinguish from other organ tumors. The case of a patient with an
      extramural gastrointestinal stromal tumor of the duodenum that mimicked a
      pancreatic head tumor has previously been reported. Here, we report a rare case
      of a patient with a duodenal gastrointestinal stromal tumor with extramural
      growth that mimicked a pancreatic neuroendocrine tumor. In this case, the
      gastrointestinal stromal tumor was also associated with neurofibromatosis type 1
      (also known as von Recklinghausen's disease). To the best of our knowledge, this
      is the first report to describe the case of a patient with a duodenal
      gastrointestinal stromal tumor with neurofibromatosis type 1 in which the
      radiological findings resembled those of a pancreatic neuroendocrine tumor. CASE
      PRESENTATION: A 60-year-old Japanese woman with a history of neurofibromatosis
      type 1 was admitted to our hospital for the treatment of a tumor of her pancreas.
      She had no symptoms, but an abdominal ultrasonography screening examination had
      revealed a hypoechoic mass in the head of her pancreas. Laboratory data,
      including tumor markers, were within the normal ranges, and her insulin and
      glucagon levels were also within the normal ranges. However, her plasma gastrin
      level was elevated at 580 pg/mL (30 to 150 pg/mL). A computed tomography
      examination revealed a hypervascular tumor measuring 14 mm in diameter in the
      head of her pancreas. We diagnosed the patient as having a pancreatic
      neuroendocrine tumor and performed a tumor resection with a duodenal wedge
      resection. Microscopic analysis revealed spindle cell tumors in a trabecular
      pattern. The patient was finally diagnosed as having a duodenal gastrointestinal
      stromal tumor of the uncommitted type. CONCLUSION: Extramural growth-type
      gastrointestinal stromal tumors can be difficult to distinguish from other organ
      tumors. In our case, a duodenal gastrointestinal stromal tumor was difficult to
      distinguish from a pancreatic neuroendocrine tumor based on radiological
      findings. When patients are identified as having hypervascular lesions that have
      adhered to the gastrointestinal tract, the possibility of an extramural growth
      type gastrointestinal stromal tumor as a differential diagnosis should be
      considered in patients with neurofibromatosis type 1.

PMID- 20825632
TI  - Photochemical tissue bonding with chitosan adhesive films.
AB  - BACKGROUND: Photochemical tissue bonding (PTB) is a promising sutureless
      technique for tissue repair. PTB is often achieved by applying a solution of rose
      bengal (RB) between two tissue edges, which are irradiated by a green laser to
      crosslink collagen fibers with minimal heat production. In this study, RB has
      been incorporated in chitosan films to create a novel tissue adhesive that is
      laser-activated. METHODS: Adhesive films, based on chitosan and containing ~0.1
      wt% RB were manufactured and bonded to calf intestine by a solid state laser
      (lambda = 532 nm, Fluence~110 J/cm2, spot size~0.5 cm). A single-column
      tensiometer, interfaced with a personal computer, tested the bonding strength. K
      type thermocouples recorded the temperature (T) at the adhesive-tissue interface
      during laser irradiation. Human fibroblasts were also seeded on the adhesive and
      cultured for 48 hours to assess cell growth. RESULTS: The RB-chitosan adhesive
      bonded firmly to the intestine with adhesion strength of 15 +/- 2 kPa, (n = 31).
      The adhesion strength dropped to 0.5 +/- 0.1 (n = 8) kPa when the laser was not
      applied to the adhesive. The average temperature of the adhesive increased from
      26 degrees C to 32 degrees C during laser exposure. Fibroblasts grew confluent on
      the adhesive without morphological changes. CONCLUSION: A new biocompatible
      chitosan adhesive has been developed that bonds photochemically to tissue with
      minimal temperature increase.

PMID- 20825633
TI  - Fatty acids, membrane viscosity, serotonin and ischemic heart disease.
AB  - Novel markers for ischemic heart disease are under investigation by the
      scientific community at international level.This work focuses on a specific
      platelet membrane fatty acid condition of viscosity which is linked to molecular
      aspects such as serotonin and G proteins, factors involved in vascular biology.A
      suggestive hypothesis is considered about the possibility to use platelet
      membrane viscosity, in relation to serotonin or, indirectly, the fatty acid
      profile, as indicator of ischemic risk.

PMID- 20825634
TI  - Ethnic differences in dissatisfaction with sexual life in patients with type 2
      diabetes in a Swedish town.
AB  - BACKGROUND: The first aim of this study was to analyze whether self-reported
      satisfaction with one's sexual life was associated with ethnicity (Swedish and
      Assyrian/Syrian) in patients with type 2 diabetes. The second was to study
      whether the association between satisfaction with one's sexual life and ethnicity
      remained after controlling for possible confounders such as marital status,
      HbA1c, medication, and presence of other diseases. METHODS: This cross-sectional,
      questionnaire-based study was conducted at four primary health care centers in
      the Swedish town of Sodertalje. A total of 354 persons (173 ethnic
      Assyrians/Syrians and 181 ethnic Swedes) participated. RESULTS: The total
      prevalence of self-reported dissatisfaction with one's sexual life in both groups
      was 49%. No significant ethnic differences were found in the outcome. In the
      final model, regardless of ethnicity, the odds ratio (OR) for self-reported
      dissatisfaction with one's sexual life in those >= 70 years old was 2.52 (95% CI
      1.33-4.80). Among those living alone or with children, the OR was more than three
      times higher than for married or cohabiting individuals (OR = 3.10, 95% CI 1.60
      6.00). Those with other diseases had an OR 1.89 times (95% CI 1.10-3.40) higher
      than those without other diseases. CONCLUSIONS: The findings demonstrate that
      almost half of participants were dissatisfied with their sexual life and
      highlight the importance of sexual life to people with type 2 diabetes. This
      factor should not be ignored in clinical evaluations. Moreover, the findings
      demonstrate that it is possible to include questions on sexual life in
      investigations of patients with type 2 diabetes and even in other health-related,
      questionnaire studies, despite the sensitivity of the issue of sexuality.

PMID- 20825635
TI  - Patient-to-patient transmission of hepatitis C virus (HCV) during colonoscopy
      diagnosis.
AB  - BACKGROUND: No recognized risk factors can be identified in 10-40% of hepatitis C
      virus (HCV)-infected patients suggesting that the modes of transmission involved
      could be underestimated or unidentified. Invasive diagnostic procedures, such as
      endoscopy, have been considered as a potential HCV transmission route; although
      the actual extent of transmission in endoscopy procedures remains controversial.
      Most reported HCV outbreaks related to nosocomial acquisition have been
      attributed to unsafe injection practices and use of multi-dose vials. Only a few
      cases of likely patient-to-patient HCV transmission via a contaminated
      colonoscope have been reported to date. Nosocomial HCV infection may have
      important medical and legal implications and, therefore, possible transmission
      routes should be investigated. In this study, a case of nosocomial transmission
      of HCV from a common source to two patients who underwent colonoscopy in an
      endoscopy unit is reported. RESULTS: A retrospective epidemiological search after
      detection of index cases revealed several potentially infective procedures:
      sample blood collection, use of a peripheral catheter, anesthesia and colonoscopy
      procedures. The epidemiological investigation showed breaches in colonoscope
      reprocessing and deficiencies in the recording of valuable tracing data. Direct
      sequences from the NS5B region were obtained to determine the extent of the
      outbreak and cloned sequences from the E1-E2 region were used to establish the
      relationships among intrapatient viral populations. Phylogenetic analyses of
      individual sequences from viral populations infecting the three patients involved
      in the outbreak confirmed the patient pointed out by the epidemiological search
      as the source of the outbreak. Furthermore, the sequential order in which the
      patients underwent colonoscopy correlates with viral genetic variability
      estimates. CONCLUSIONS: Patient-to-patient transmission of HCV could be
      demonstrated although the precise route of transmission remained unclear. Viral
      genetic variability is proposed as a useful tool for tracing HCV transmission,
      especially in recent transmissions.

PMID- 20825636
TI  - Interleukin-10 gene down-expression in circulating mononuclear cells during
      infusion of drotrecogin-alpha activated: a pilot study.
AB  - INTRODUCTION: The purpose of this study was to investigate the gene expression of
      interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-10 (IL-10) in circulating mononuclear cells harvested from septic
      shock patients on drotrecogin-alpha activated (DAA) in order to determine whether
      this treatment has any effect on the inflammation phase. METHODS: We conducted a
      prospective cohort study in two intensive care departments. Blood samples were
      collected at inclusion (T1) and 36 hours later (T2) to measure plasma cytokines
      and the changes in intracellular TNF-alpha, IL-10 and IFN-gamma mRNA expressions
      using the real-time quantitative polymerase chain reaction (RT-qPCR). Thirty-two
      septic shock patients were included: 16 with DAA at 24 MUg/kg/h for 96 hours
      (DAA+) and 16 control (DAA-) eligible but contraindicated for DAA because of low
      platelet count. RESULTS: The basal characteristics were similar in both groups:
      mortality (50%), plasma cytokine concentrations, and baseline IFN-gamma, TNF
      alpha and IL-10 mRNA expressions (DAA+ vs. DAA-). At T2, there was a significant
      IFN-gamma gene down-regulation in DAA+ but not in DAA- patients (-0.34 (-0.62;
      +1.54) vs. +1.41 (+0.35; +5.87), P = 0.008). In survivors, DAA administration was
      associated with a down-expression of both IFN-gamma (-0.65 (-0.93; 0.48) vs. +0.7
      (-0.04; +1.26), P = 0.01) and IL-10 (-0.78 (-0.92; -0.6) vs. -0.18 (-0.68;
      +0.46), P = 0.038). In the non-survivors, DAA infusion was associated with IL-10
      over-expression when compared with survivors (+0.54 (-0.35; +11.52) vs. -0.78 (
      0.92; -0.6), P < 0.001). CONCLUSIONS: In this study, lack of IL-10 gene down
      expression despite a 36-hour infusion of DAA is an ominous sign in septic shock
      patients suggesting that DAA is not able to reverse the outcome. Our results
      suggest that DAA can decrease the expression of anti-inflammatory cytokines in
      septic shock patients. IL-10 or IFN-gamma gene down-expression could represent
      markers of DAA response.

PMID- 20825637
TI  - Asymmetric and non-uniform evolution of recently duplicated human genes.
AB  - BACKGROUND: Gene duplications are a source of new genes and protein functions.
      The innovative role of duplication events makes families of paralogous genes an
      interesting target for studies in evolutionary biology. Here we study global
      trends in the evolution of human genes that resulted from recent duplications.
      RESULTS: The pressure of negative selection is weaker during a short time
      immediately after a duplication event. Roughly one fifth of genes in paralogous
      gene families are evolving asymmetrically: one of the proteins encoded by two
      closest paralogs accumulates amino acid substitutions significantly faster than
      its partner. This asymmetry cannot be explained by differences in gene expression
      levels. In asymmetric gene pairs the number of deleterious mutations is increased
      in one copy, while decreased in the other copy as compared to genes constituting
      non-asymmetrically evolving pairs. The asymmetry in the rate of synonymous
      substitutions is much weaker and not significant. CONCLUSIONS: The increase of
      negative selection pressure over time after a duplication event seems to be a
      major trend in the evolution of human paralogous gene families. The observed
      asymmetry in the evolution of paralogous genes shows that in many cases one of
      two gene copies remains practically unchanged, while the other accumulates
      functional mutations. This supports the hypothesis that slowly evolving gene
      copies preserve their original functions, while fast evolving copies obtain new
      specificities or functions.

PMID- 20825638
TI  - Posterior cruciate ligament mediated avulsion fracture of the lateral tibial
      condyle: a case report.
AB  - Avulsion fractures of the posterior cruciate ligament (PCL) are uncommon. On the
      basis of the site of damage of the PCL, hyperflexion, pretibial trauma, and
      hyperextension are proposed as mechanisms of PCL injuries. On the other hand,
      avulsion fractures of the tibial condyle are also rare. We report a PCL-mediated
      avulsion fracture of the lateral tibial condyle along with the tibial insertion
      of the PCL by extension-distraction force on the knee that has not been
      previously described in any study. This rare case may imply that application of
      an extension-distraction force to the PCL cause the avulsion fracture.

PMID- 20825639
TI  - Chondroprotective effects and mechanisms of resveratrol in advanced glycation end
      products-stimulated chondrocytes.
AB  - INTRODUCTION: Accumulation of advanced glycation end products (AGEs) in joints
      contributes to the pathogenesis of cartilage damage in osteoarthritis (OA). We
      aim to explore the potential chondroprotective effects of resveratrol on AGEs
      stimulated porcine chondrocytes and cartilage explants. METHODS: Chondrocytes
      were isolated from pig joints. Activation of the IkappaB kinase (IKK)
      IkappaBalpha-nuclear factor-kappaB (NF-kappaB) and c-Jun N-terminal kinase
      (JNK)/extracellular signal-regulated kinase (ERK)-activator protein-1 (AP-1)
      pathways was assessed by electrophoretic mobility shift assay (EMSA), Western
      blot and transfection assay. The levels of inducible nitric oxide synthase (iNOS)
      NO and cyclooxygenase-2 (COX-2)-prostaglandin E2 (PGE2) were measured by Western
      blot, Griess reaction or ELISA. The expression and enzyme activity of matrix
      metalloproteinase-13 (MMP-13) were determined by real time RT/PCR and gelatin
      zymography, respectively. RESULTS: We show that AGEs-induced expression of iNOS
      and COX-2 and production of NO and PGE2 were suppressed by resveratrol. Such
      effects of resveratrol were likely mediated through inhibiting IKK-IkappaBalpha
      NF-kappaB and JNK/ERK-AP-1 signaling pathways induced by AGEs. By targeting these
      critical signaling pathways, resveratrol decreased AGEs-stimulated expression and
      activity of MMP-13 and prevented AGEs-mediated destruction of collagen II.
      Histochemistry analysis further confirms that resveratrol could prevent AGEs
      induced degradation of proteoglycan and aggrecan in cartilage explants.
      CONCLUSIONS: The present study reveals not only the effects and mechanisms
      regarding how resveratrol may protect cartilage from AGEs-mediated damage but
      also the potential therapeutic benefit of resveratrol in the treatment of OA.

PMID- 20825640
TI  - Occupational cataracts and lens opacities in interventional cardiology (O'CLOC
      study): are X-Rays involved? Radiation-induced cataracts and lens opacities.
AB  - BACKGROUND: The eye is well known to be sensitive to clearly high doses (>2 Gy)
      of ionizing radiation. In recent years, however, cataracts have been observed in
      populations exposed to lower doses. Interventional cardiologists are repeatedly
      and acutely exposed to scattered ionizing radiation (X-rays) during the
      diagnostic and therapeutic procedures they perform. These "low" exposures may
      cause damage to the lens of the eye and induce early cataracts, known as
      radiation-induced cataracts. The O'CLOC study (Occupational Cataracts and Lens
      Opacities in interventional Cardiology) was designed to test the hypothesis that
      interventional cardiologists, compared with an unexposed reference group of non
      interventional cardiologists, have an increased risk of cataracts. METHOD/DESIGN:
      The O'CLOC study is a cross-sectional study that will include a total of 300
      cardiologists aged at least 40 years: one group of exposed interventional
      cardiologists and another of non-interventional cardiologists. The groups will be
      matched for age and sex. Individual information, including risk factors for
      cataracts (age, diabetes, myopia, etc.), will be collected during a telephone
      interview. A specific section of the questionnaire for the exposed group focuses
      on occupational history, including a description of the procedures (type,
      frequency, radiation protection tool) used. These data will be used to classify
      subjects into "exposure level" groups according to cumulative dose estimates. Eye
      examinations for all participants will be performed to detect cataracts, even in
      the early stages (lens opacities, according to LOCS III, the international
      standard classification). The analysis will provide an estimation of the cataract
      risk in interventional cardiology compared with the unexposed reference group,
      while taking other risk factors into account. An analysis comparing the risks
      according to level of exposure is also planned. DISCUSSION: This epidemiological
      study will provide further evidence about the potential risk of radiation-induced
      cataracts at low doses and contribute to cardiologists' awareness of the
      importance of radiation protection. TRIAL REGISTRATION: NCT01061463.

PMID- 20825641
TI  - Simple and flexible classification of gene expression microarrays via Swirls and
      Ripples.
AB  - BACKGROUND: A simple classification rule with few genes and parameters is
      desirable when applying a classification rule to new data. One popular simple
      classification rule, diagonal discriminant analysis, yields linear or curved
      classification boundaries, called Ripples, that are optimal when gene expression
      levels are normally distributed with the appropriate variance, but may yield poor
      classification in other situations. RESULTS: A simple modification of diagonal
      discriminant analysis yields smooth highly nonlinear classification boundaries,
      called Swirls, that sometimes outperforms Ripples. In particular, if the data are
      normally distributed with different variances in each class, Swirls substantially
      outperforms Ripples when using a pooled variance to reduce the number of
      parameters. The proposed classification rule for two classes selects either
      Swirls or Ripples after parsimoniously selecting the number of genes and distance
      measures. Applications to five cancer microarray data sets identified predictive
      genes related to the tissue organization theory of carcinogenesis. CONCLUSION:
      The parsimonious selection of classifiers coupled with the selection of either
      Swirls or Ripples provides a good basis for formulating a simple, yet flexible,
      classification rule. Open source software is available for download.

PMID- 20825642
TI  - Suppression subtractive hybridization analysis reveals expression of conserved
      and novel genes in male accessory glands of the ant Leptothorax gredleri.
AB  - BACKGROUND: During mating, insect males eject accessory gland proteins (Acps)
      into the female genital tract. These substances are known to affect female post
      mating behavior and physiology. In addition, they may harm the female, e.g., in
      reducing its lifespan. This is interpreted as a consequence of sexual
      antagonistic co-evolution. Whereas sexual conflict abounds in non-social species,
      the peculiar life history of social insects (ants, bees, wasps) with lifelong
      pair-bonding and no re-mating aligns the reproductive interests of the sexes.
      Harming the female during mating would negatively affect male fitness and sexual
      antagonism is therefore not expected. Indeed, mating appears to increase female
      longevity in at least one ant species. Acps are presumed to play a role in this
      phenomenon, but the underlying mechanisms are unknown. In this study, we
      investigated genes, which are preferentially expressed in male accessory glands
      of the ant Leptothorax gredleri, to determine which proteins might be transferred
      in the seminal fluid. RESULTS: By a suppression subtractive hybridization
      protocol we obtained 20 unique sequences (USs). Twelve had mutual best matches
      with genes predicted for Apis mellifera and Nasonia vitripennis. Functional
      information (Gene Ontology) was available only for seven of these, including
      intracellular signaling, energy-dependent transport and metabolic enzyme
      activities. The remaining eight USs did not match sequences from other species.
      Six genes were further analyzed by quantitative RT-PCR in three life cycle stages
      of male ants. A gene with carboxy-lyase activity and one of unpredicted function
      were significantly overexpressed in accessory glands of sexually mature males.
      CONCLUSIONS: Our study is the first one to investigate differential gene
      expression in ants in a context related to mating. Our findings indicate that
      male accessory glands of L. gredleri express a series of genes that are unique to
      this species, possibly representing novel genes, in addition to conserved ones
      for which functions can be predicted. Identifying differentially expressed genes
      might help to better understand molecular mechanisms involved in reproductive
      processes in eusocial Hymenoptera. While the novel genes could account for
      rapidly evolving ones driven by intra-sexual conflict between males, conserved
      genes imply that rather beneficial traits might get fixed by a process described
      as inter-sexual cooperation between males and females.

PMID- 20825643
TI  - Administration of single-dose GnRH agonist in the luteal phase in ICSI cycles: a
      meta-analysis.
AB  - BACKGROUND: The effects of gonadotrophin-releasing hormone agonist (GnRH-a)
      administered in the luteal phase remains controversial. This meta-analysis aimed
      to evaluate the effect of the administration of a single-dose of GnRH-a in the
      luteal phase on ICSI clinical outcomes. METHODS: The research strategy included
      the online search of databases. Only randomized studies were included. The
      outcomes analyzed were implantation rate, clinical pregnancy rate (CPR) per
      transfer and ongoing pregnancy rate. The fixed effects model was used for odds
      ratio. In all trials, a single dose of GnRH-a was administered at day 5/6 after
      ICSI procedures. RESULTS: All cycles presented statistically significantly higher
      rates of implantation (P<0.0001), CPR per transfer (P=0.006) and ongoing
      pregnancy (P=0.02) in the group that received luteal-phase GnRH-a administration
      than in the control group (without luteal-phase-GnRH-a administration). When meta
      analysis was carried out only in trials that had used long GnRH-a ovarian
      stimulation protocol, CPR per transfer (P=0.06) and ongoing pregnancy (P=0.23)
      rates were not significantly different between the groups, but implantation rate
      was significant higher (P=0.02) in the group that received luteal-phase-GnRH-a
      administration. On the other hand, the results from trials that had used GnRH
      antagonist multi-dose ovarian stimulation protocol showed statistically
      significantly higher implantation (P=0.0002), CPR per transfer (P=0.04) and
      ongoing pregnancy rate (P=0.04) in the luteal-phase-GnRH-a administration group.
      The majority of the results presented heterogeneity. CONCLUSIONS: These findings
      demonstrate that the luteal-phase single-dose GnRH-a administration can increase
      implantation rate in all cycles and CPR per transfer and ongoing pregnancy rate
      in cycles with GnRH antagonist ovarian stimulation protocol. Nevertheless, by
      considering the heterogeneity between the trials, it seems premature to recommend
      the use of GnRH-a in the luteal phase. Additional randomized controlled trials
      are necessary before evidence-based recommendations can be provided.

PMID- 20825644
TI  - Appropriate cut-off value for follicle-stimulating hormone in azoospermia to
      predict spermatogenesis.
AB  - BACKGROUND: This study was undertaken to determine the optimal cut-off value for
      FSH to predict the presence of spermatogenesis in patients with non-obstructive
      azoospermia. METHODS: A total of 206 non-obstructive azoospermic men were
      enrolled in this prospective study. By using receiver operating characteristic
      (ROC) curves, we determined the optimal cut-off value for FSH and evaluated
      whether the test could adequately predict successful sperm retrieval. RESULTS:
      There were 108 non-obstructive azoospermic patients who had evidence of
      spermatogenesis (group A) and achieved success in sperm retrieval. Another 98 non
      obstructive azoospermic patients (group B) failed in sperm retrieval. The mean
      value of serum FSH in group B was significantly higher than in group A (28.03 +/-
      14.56 mIU/mL vs 7.94 +/- 4.95 mIU/mL, p < 0.01; respectively). The area under the
      receiver operating characteristic curves were 0.939 +/- 0.02 and a cut-off value
      of 19.4 mIU/mL discriminated between group A and B with a sensitivity of 70%. The
      positive predictive value for failed sperm retrieval (group B) can reach 100%.
      CONCLUSIONS: Elevated plasma levels of FSH of more than 19.4 mIU/mL could be used
      as a reliable criterion for a trial of sperm retrieval from testes in artificial
      reproductive techniques.

PMID- 20825645
TI  - Front-of-pack nutrition label stimulates healthier product development: a
      quantitative analysis.
AB  - BACKGROUND: In addition to helping consumers make healthier food choices, front
      of-pack nutrition labels could encourage companies to reformulate existing
      products and develop new ones with a healthier product composition. This is the
      largest study to date to investigate the effect of a nutrition logo on the
      development of healthier products by food manufacturers. METHODS: A total of 47
      food manufacturers joining the Choices Foundation in the Netherlands (response:
      39.5%) indicated whether their Choices products were newly developed,
      reformulated or already complied with the Choices criteria and provided nutrient
      composition data for their products (n = 821; 23.5% of the available Choices
      products in August 2009). RESULTS: Most products carrying the logo as a result of
      reformulation and new product development were soups and snacks. Sodium reduction
      was the most common change found in processed meats, sandwiches, soups and
      sandwich fillings. Dietary fiber was significantly increased in most newly
      developed Choices product groups; for example, in fruit juices, processed meats,
      dairy products, sandwiches and soups. Saturated fatty acids (SAFA) and added
      sugar were significantly decreased both in reformulated and newly developed dairy
      products. Caloric content was significantly decreased only in reformulated dairy
      products, sandwich fillings and in some newly developed snacks. CONCLUSIONS: The
      results indicate that the Choices logo has motivated food manufacturers to
      reformulate existing products and develop new products with a healthier product
      composition, especially where sodium and dietary fiber are concerned.

PMID- 20825646
TI  - Compensation patterns following occupational injuries in Zambia: results from the
      2009 Labour Survey.
AB  - BACKGROUND: Occupational injuries have received limited research attention in the
      Southern African Development Community. Much of the published data come from
      South Africa and little has been reported elsewhere within the region. The
      present study was conducted to estimate the prevalence rates of occupational
      injuries and compensation; and to determine factors associated with occupational
      injuries and compensation. METHODS: Data were obtained from occupational health
      and injury questions added to the Zambian Labour Force Survey of 2009 by the Work
      and Health in Southern Africa programme. Logistic regression analyses were
      conducted to determine the degree of association between demographic, social and
      economic factors on one hand and injury and compensation on the other. RESULTS:
      Data on 61871 study participants were available for analysis, of whom 4998 (8.1%)
      reported having been injured (10.0% of males, and 6.2% of females) due to work in
      the previous 12 months to the survey. Of those injured, 60.5% reported having
      stayed away from work as a result. The commonest type of injury was "open wound"
      (81.6%). Male gender, being married or married before, being a paid employee,
      working for a private company and household were positively associated with
      serious injuries. Injuries also varied by geographical area. Factors positively
      associated with receiving compensation for work-related injuries were: male
      gender, Copperbelt and North-Western provinces, and unpaid family worker.
      Employer/self employed and having less than 5 employees in a workplace were
      negatively associated with compensation. CONCLUSION: The prevalence of reported
      injury and its association with a significant level of absence from work,
      indicate that occupational hazards in Zambia have significant health and economic
      effects. Female workers should equally be compensated for injuries suffered as
      their male counterparts.

PMID- 20825648
TI  - Opening the black box of quality improvement collaboratives: an Actor-Network
      theory approach.
AB  - BACKGROUND: Quality improvement collaboratives are often labeled as black boxes
      because effect studies usually do not describe exactly how the results were
      obtained. In this article we propose a way of opening such a black box, by taking
      up a dynamic perspective based on Actor-Network Theory. We thereby analyze how
      the problematisation process and the measurement practices are constructed.
      Findings from this analysis may have consequences for future evaluation studies
      of collaboratives. METHODS: In an ethnographic design we probed two projects
      within a larger quality improvement collaborative on long term mental health care
      and care for the intellectually disabled. Ethnographic observations were made at
      nine national conferences. Furthermore we conducted six case studies involving
      participating teams. Additionally, we interviewed the two program leaders of the
      overall projects. RESULTS: In one project the problematisation seemed to undergo
      a shift of focus away from the one suggested by the project leaders. In the other
      we observed multiple roles of the measurement instrument used. The instrument did
      not only measure effects of the improvement actions but also changed these
      actions and affected the actors involved. CONCLUSIONS: Effectiveness statistics
      ideally should be complemented with an analysis of the construction of the
      collaborative and the improvement practices. Effect studies of collaboratives
      could benefit from a mixed methods research design that combines quantitative and
      qualitative methods.

PMID- 20825647
TI  - Multiple sites in the N-terminal half of simian immunodeficiency virus capsid
      protein contribute to evasion from rhesus monkey TRIM5alpha-mediated restriction.
AB  - BACKGROUND: We previously reported that cynomolgus monkey (CM) TRIM5alpha could
      restrict human immunodeficiency virus type 2 (HIV-2) strains carrying a proline
      at the 120th position of the capsid protein (CA), but it failed to restrict those
      with a glutamine or an alanine. In contrast, rhesus monkey (Rh) TRIM5alpha could
      restrict all HIV-2 strains tested but not simian immunodeficiency virus isolated
      from macaque (SIVmac), despite its genetic similarity to HIV-2. RESULTS: We
      attempted to identify the viral determinant of SIVmac evasion from Rh TRIM5alpha
      mediated restriction using chimeric viruses formed between SIVmac239 and HIV-2
      GH123 strains. Consistent with a previous study, chimeric viruses carrying the
      loop between alpha-helices 4 and 5 (L4/5) (from the 82nd to 99th amino acid
      residues) of HIV-2 CA were efficiently restricted by Rh TRIM5alpha. However, the
      corresponding loop of SIVmac239 CA alone (from the 81st to 97th amino acid
      residues) was not sufficient to evade Rh TRIM5alpha restriction in the HIV-2
      background. A single glutamine-to-proline substitution at the 118th amino acid of
      SIVmac239 CA, corresponding to the 120th amino acid of HIV-2 GH123, also
      increased susceptibility to Rh TRIM5alpha, indicating that glutamine at the 118th
      of SIVmac239 CA is necessary to evade Rh TRIM5alpha. In addition, the N-terminal
      portion (from the 5th to 12th amino acid residues) and the 107th and 109th amino
      acid residues in alpha-helix 6 of SIVmac CA are necessary for complete evasion
      from Rh TRIM5alpha-mediated restriction. A three-dimensional model of hexameric
      GH123 CA showed that these multiple regions are located on the CA surface,
      suggesting their direct interaction with TRIM5alpha. CONCLUSION: We found that
      multiple regions of the SIVmac CA are necessary for complete evasion from Rh
      TRIM5alpha restriction.

PMID- 20825649
TI  - ErbB2 enhances mammary tumorigenesis, oncogene-independent recurrence and
      metastasis in a model of IGF-IR-mediated mammary tumorigenesis.
AB  - BACKGROUND: The type I insulin-like growth factor receptor (IGF-IR) and ErbB2
      (Her-2) are receptor tyrosine kinases implicated in human breast cancer. Both
      proteins are currently the subject of targeted therapeutics that are used in the
      treatment of breast cancer or which are in clinical trials. The focus of this
      study was to utilize our inducible model of IGF-IR overexpression to explore the
      interaction of these two potent oncogenes. RESULTS: ErbB2 was overexpressed in
      our RM11A cell line, a murine tumor cell line that overexpresses human IGF-IR in
      an inducible manner. ErbB2 conferred an accelerated tumor onset and increased
      tumor incidence after injection of RM11A cells into the mammary glands of
      syngeneic wild type mice. This was associated with increased proliferation
      immediately after tumor cell colonization of the mammary gland; however, this
      effect was lost after tumor establishment. ErbB2 overexpression also impaired the
      regression of established RM11A tumors following IGF-IR downregulation and
      enhanced their metastatic potential. CONCLUSION: This study has revealed that
      even in the presence of vast IGF-IR overexpression, a modest increase in ErbB2
      can augment tumor establishment in vivo, mediate resistance to IGF-IR
      downregulation and facilitate metastasis. This supports the growing evidence
      suggesting a possible advantage of using IGF-IR and ErbB2-directed therapies
      concurrently in the treatment of breast cancer.

PMID- 20825650
TI  - Interleukin 2-regulated in vitro antibody production following a single spinal
      manipulative treatment in normal subjects.
AB  - BACKGROUND: Our recent investigations have demonstrated that cell cultures from
      subjects, who received a single spinal manipulative treatment in the upper
      thoracic spine, show increased capacity for the production of the key
      immunoregulatory cytokine, interleukin-2. However, it has not been determined if
      such changes influence the response of the immune effector cells. Thus, the
      purpose of the present study was to determine whether, in the same subjects,
      spinal manipulation-related augmentation of the in vitro interleukin-2 synthesis
      is associated with the modulation of interleukin 2-dependent and/or interleukin-2
      induced humoral immune response (antibody synthesis). METHODS: A total of seventy
      four age and sex-matched healthy asymptomatic subjects were studied. The subjects
      were assigned randomly to: venipuncture control (n = 22), spinal manipulative
      treatment without cavitation (n = 25) or spinal manipulative treatment associated
      with cavitation (n = 27) groups. Heparinized blood samples were obtained from the
      subjects before (baseline) and then at 20 minutes and 2 hours post-treatment.
      Immunoglobulin (antibody) synthesis was induced in cultures of peripheral blood
      mononuclear cells by stimulation with conventional pokeweed mitogen or by
      application of human recombinant interleukin-2. Determinations of the levels of
      immunoglobulin G and immunoglobulin M production in culture supernatants were
      performed by specific immunoassays. RESULTS: The baseline levels of
      immunoglobulin synthesis induced by pokeweed mitogen or human recombinant
      interleukin-2 stimulation were comparable in all groups. No significant changes
      in the production of pokeweed mitogen-induced immunoglobulins were observed
      during the post-treatment period in any of the study groups. In contrast, the
      production of interleukin-2 -induced immunoglobulin G and immunoglobulin M was
      significantly increased in cultures from subjects treated with spinal
      manipulation. At 20 min post-manipulation, immunoglobulin G synthesis was
      significantly elevated in subjects who received manipulation with cavitation,
      relative to that in cultures from subjects who received manipulation without
      cavitation and venipuncture alone. At 2 hr post-treatment, immunoglobulin M
      synthesis was significantly elevated in subjects who received manipulation with
      cavitation relative to the venipuncture group. There were no quantitative
      alterations within the population of peripheral blood B or T lymphocytes in the
      studied cultures. CONCLUSION: Spinal manipulative treatment does not increase
      interleukin-2 -dependent polyclonal immunoglobulin synthesis by mitogen-activated
      B cells. However, antibody synthesis induced by interleukin-2 alone can be, at
      least temporarily, augmented following spinal manipulation. Thus, under certain
      physiological conditions spinal manipulative treatment might influence
      interleukin-2 -regulated biological responses.

PMID- 20825653
TI  - The IGF1 small dog haplotype is derived from Middle Eastern grey wolves: a closer
      look at statistics, sampling, and the alleged Middle Eastern origin of small
      dogs.
AB  - This paper is a response to Gray MM, Sutter NB, Ostrander EA, Wayne RK: The IGF1
      small dog haplotype is derived from Middle Eastern grey wolves. BMC Biology 2010,
      8:16. See research article at http://www.biomedcentral.com/1741-7007/8/16.

PMID- 20825652
TI  - Lack of association between peroxisome proliferator-activated receptors alpha and
      gamma2 polymorphisms and progressive liver damage in patients with non-alcoholic
      fatty liver disease: a case control study.
AB  - BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) play key roles in
      the pathogenesis of nonalcoholic fatty liver disease (NAFLD). AIM: to assess the
      effect of functional single nucleotide polymorphisms (SNPs) of PPARalpha and
      PPARgamma2, previously associated with insulin resistance and dyslipidemia, on
      liver damage in NAFLD, whose progression is influenced by metabolic abnormalities
      and inherited factors. METHODS: The Leu162Val PPARalpha and Pro12Ala PPARgamma2
      SNPs were evaluated by restriction analysis. We considered 202 Italian patients
      with biopsy-proven NAFLD. RESULTS: The frequency of the evaluated SNPs did not
      differ between patients and 346 healthy controls. The presence of the PPARalpha
      162Val allele (prevalence 57%), but not of the PPARgamma2 12Ala allele
      (prevalence 18%), was associated with higher insulin resistance (HOMA-IR index
      4.71 +/- 3.8 vs. 3.58 +/- 2.7, p = 0.026), but not with hyperglycemia. The
      PPARalpha 162Val and PPARgamma2 12Ala alleles were not associated with the
      severity of steatosis, necroinflammation, or fibrosis. CONCLUSIONS: The presence
      of the PPARalpha 162Val allele was associated with insulin resistance, but not
      with liver damage in NAFLD. Because of the limited power of the present sample,
      larger studies are needed to exclude a minor effect of the PPARgamma2 12Ala
      allele on necroinflammation/fibrosis in NAFLD.

PMID- 20825654
TI  - Response to klutsch and crapon de caprona.

PMID- 20825655
TI  - Cerebrospinal fluid antibodies to aquaporin-4 in neuromyelitis optica and related
      disorders: frequency, origin, and diagnostic relevance.
AB  - BACKGROUND: In 70-80% of cases, neuromyelitis optica (NMO) is associated with
      highly specific serum auto-antibodies to aquaporin-4 (termed AQP4-Ab or NMO-IgG).
      Recent evidence strongly suggests that AQP4-Ab are directly involved in the
      immunopathogenesis of NMO. OBJECTIVE: To assess the frequency, syndrome
      specificity, diagnostic relevance, and origin of cerebrospinal fluid (CSF) AQP4
      Ab in patients with NMO spectrum disorders (NMOSD). METHODS: 87 CSF samples from
      37 patients with NMOSD and 42 controls with other neurological diseases were
      tested for AQP4-Ab in a cell based assay using recombinant human AQP4. Twenty
      three paired CSF and serum samples from AQP4-Ab seropositive NMOSD patients were
      further analysed for intrathecal IgG synthesis to AQP4. RESULTS: AQP4-Ab were
      detectable in 68% of CSF samples from AQP4-Ab seropositive patients with NMOSD,
      but in none of the CSF samples from AQP4-Ab seronegative patients with NMOSD and
      in none of the control samples. Acute disease relapse within 30 days prior to
      lumbar puncture, AQP4-Ab serum titres >1:250, and blood-CSF barrier dysfunction,
      but not treatment status, predicted CSF AQP4-Ab positivity. A positive AQP4
      specific antibody index was present in 1/23 samples analysed. CONCLUSIONS: AQP4
      Ab are detectable in the CSF of most patients with NMOSD, mainly during relapse,
      and are highly specific for this condition. In the cohort analysed in this study,
      testing for CSF AQP4-Ab did not improve the sensitivity and specificity of the
      current diagnostic criteria for NMO. The substantial lack of intrathecal AQP4-Ab
      synthesis in patients with NMOSD may reflect the unique localisation of the
      target antigen at the blood brain barrier, and is important for our understanding
      of the immunopathogenesis of the disease.

PMID- 20825656
TI  - Mutations in matrix and SP1 repair the packaging specificity of a Human
      Immunodeficiency Virus Type 1 mutant by reducing the association of Gag with
      spliced viral RNA.
AB  - BACKGROUND: The viral genome of HIV-1 contains several secondary structures that
      are important for regulating viral replication. The stem-loop 1 (SL1) sequence in
      the 5' untranslated region directs HIV-1 genomic RNA dimerization and packaging
      into the virion. Without SL1, HIV-1 cannot replicate in human T cell lines. The
      replication restriction phenotype in the SL1 deletion mutant appears to be
      multifactorial, with defects in viral RNA dimerization and packaging in producer
      cells as well as in reverse transcription of the viral RNA in infected cells. In
      this study, we sought to characterize SL1 mutant replication restrictions and
      provide insights into the underlying mechanisms of compensation in revertants.
      RESULTS: HIV-1 lacking SL1 (NLDeltaSL1) did not replicate in PM-1 cells until two
      independent non-synonymous mutations emerged: G913A in the matrix domain (E42K)
      on day 18 postinfection and C1907T in the SP1 domain (P10L) on day 11
      postinfection. NLDeltaSL1 revertants carrying either compensatory mutation showed
      enhanced infectivity in PM-1 cells. The SL1 revertants produced significantly
      more infectious particles per nanogram of p24 than did NLDeltaSL1. The SL1
      deletion mutant packaged less HIV-1 genomic RNA and more cellular RNA,
      particularly signal recognition particle RNA, in the virion than the wild-type.
      NLDeltaSL1 also packaged 3- to 4-fold more spliced HIV mRNA into the virion,
      potentially interfering with infectious virus production. In contrast, both
      revertants encapsidated 2.5- to 5-fold less of these HIV-1 mRNA species.
      Quantitative RT-PCR analysis of RNA cross-linked with Gag in formaldehyde-fixed
      cells demonstrated that the compensatory mutations reduced the association
      between Gag and spliced HIV-1 RNA, thereby effectively preventing these RNAs from
      being packaged into the virion. The reduction of spliced viral RNA in the virion
      may have a major role in facilitating infectious virus production, thus restoring
      the infectivity of NLDeltaSL1. CONCLUSIONS: HIV-1 evolved to overcome a deletion
      in SL1 and restored infectivity by acquiring compensatory mutations in the N
      terminal matrix or SP1 domain of Gag. These data shed light on the functions of
      the N-terminal matrix and SP1 domains and suggest that both regions may have a
      role in Gag interactions with spliced viral RNA.

PMID- 20825657
TI  - Difference between pre-operative and cardiopulmonary bypass mean arterial
      pressure is independently associated with early cardiac surgery-associated acute
      kidney injury.
AB  - BACKGROUND: Cardiac surgery-associated acute kidney injury (CSA-AKI) contributes
      to increased morbidity and mortality. However, its pathophysiology remains
      incompletely understood. We hypothesized that intra-operative mean arterial
      pressure (MAP) relative to pre-operative MAP would be an important predisposing
      factor for CSA-AKI. METHODS: We performed a prospective observational study of
      157 consecutive high-risk patients undergoing cardiac surgery with
      cardiopulmonary bypass (CPB). The primary exposure was delta MAP, defined as the
      pre-operative MAP minus average MAP during CPB. Secondary exposure was CPB flow.
      The primary outcome was early CSA-AKI, defined by a minimum RIFLE class - RISK.
      Univariate and multivariate logistic regression were performed to explore for
      association between delta MAP and CSA-AKI. RESULTS: Mean (+/- SD) age was 65.9 +/
      14.7 years, 70.1% were male, 47.8% had isolated coronary bypass graft (CABG)
      surgery, 24.2% had isolated valve surgery and 16.6% had combined procedures. Mean
      (+/- SD) pre-operative, intra-operative and delta MAP were 86.6 +/- 13.2, 57.4 +/
      5.0 and 29.4 +/- 13.5 mmHg, respectively. Sixty-five patients (41%) developed
      CSA-AKI within in the first 24 hours post surgery. By multivariate logistic
      regression, a delta MAP>=26 mmHg (odds ratio [OR], 2.8; 95%CI, 1.3-6.1, p =
      0.009) and CPB flow rate >=54 mL/kg/min (OR, 0.2, 0.1-0.5, p < 0.001) were
      independently associated with CSA-AKI. Additional variables associated with CSA
      AKI included use of a side-biting aortic clamp (OR, 3.0; 1.3-7.1, p = 0.012), and
      body mass index >=25 (OR, 4.2; 1.6-11.2, p = 0.004). CONCLUSION: A large delta
      MAP and lower CPB flow during cardiac surgery are independently associated with
      early post-operative CSA-AKI in high-risk patients. Delta MAP represents a
      potentially modifiable intra-operative factor for development of CSA-AKI that
      necessitates further inquiry.

PMID- 20825658
TI  - Single site laparoscopic right hemicolectomy: an oncological feasible option.
AB  - INTRODUCTION: We present the first 7 cases of single site right hemicolectomy in
      Asia using the new Single Site Laparoscopy (SSL) access system from Ethicon Endo
      surgery. METHODS: Right hemicolectomy was performed using the new Single Site
      Laparoscopy (SSL) access system. Patient demographics, operative time, histology
      and post operative recovery and complications were collected and analysed.
      RESULTS: The median operative time was 90 mins (range 60 - 150 mins) and a median
      wound size of 2.5 cm (range 2 to 4.5 cm). The median number of lymph nodes
      harvested was 24 (range 20 to 34 lymph nodes). The median length of proximal
      margin was 70 mm (range 30 to 145 mm) and that of distal margin was 50 mm (35 to
      120 mm). All patients had a median hospital stay of 7 days (range 5 to 11) and
      there were no significant perioperative complications except for 1 patient who
      had a minor myocardial event. CONCLUSION: Right hemicolectomy using SSL access
      system is feasible and safe for oncologic surgery.

PMID- 20825659
TI  - Menin and RNF20 recruitment is associated with dynamic histone modifications that
      regulate signal transducer and activator of transcription 1 (STAT1)-activated
      transcription of the interferon regulatory factor 1 gene (IRF1).
AB  - BACKGROUND: Signal transducer and activator of transcription (STAT) activation of
      gene expression is both rapid and transient, and when properly executed it
      affects growth, differentiation, homeostasis and the immune response, but when
      dysregulated it contributes to human disease. Transcriptional activation is
      regulated by alterations to the chromatin template. However, the role of histone
      modification at gene loci that are activated for transcription in response to
      STAT signaling is poorly defined. RESULTS: Using chromatin immunoprecipitation,
      we profiled several histone modifications during STAT1 activation of the
      interferon regulatory factor 1 gene (IRF1). Methylated lysine histone proteins
      H3K4me2, H3K4me3, H3K79me3, H3K36me3 and monoubiquitinated histone ubH2B are
      dynamic and correlate with interferon (IFN)gamma induction of STAT1 activity.
      Chemical inhibition of H3K4 methylation downregulates IRF1 transcription and
      decreases RNA polymerase II (Pol II) occupancy at the IRF1 promoter. MEN1, a
      component of a complex proteins associated with Set1 (COMPASS)-like complex and
      the hBRE1 component, RNF20, are localized to IRF1 in the uninduced state and are
      further recruited when IRF1 is activated. RNAi-mediated depletion of RNF20 lowers
      both ubH2B and H3K4me3, but surprisingly, upregulates IFNgamma induced IRF1
      transcription. The dynamics of phosphorylation in the C-terminal domain (CTD) of
      Pol II are disrupted during gene activation as well. CONCLUSIONS: H2B
      monoubiquitination promotes H3K4 methylation, but the E3 ubiquitin ligase, RNF20,
      is repressive of inducible transcription at the IRF1 gene locus, suggesting that
      ubH2B can, directly or indirectly, affect Pol II CTD phosphorylation cycling to
      exert control on ongoing transcription.

PMID- 20825660
TI  - The effectiveness of interventions to change six health behaviours: a review of
      reviews.
AB  - BACKGROUND: Several World Health Organisation reports over recent years have
      highlighted the high incidence of chronic diseases such as diabetes, coronary
      heart disease and cancer. Contributory factors include unhealthy diets, alcohol
      and tobacco use and sedentary lifestyles. This paper reports the findings of a
      review of reviews of behavioural change interventions to reduce unhealthy
      behaviours or promote healthy behaviours. We included six different health
      related behaviours in the review: healthy eating, physical exercise, smoking,
      alcohol misuse, sexual risk taking (in young people) and illicit drug use. We
      excluded reviews which focussed on pharmacological treatments or those which
      required intensive treatments (e.g. for drug or alcohol dependency). METHODS: The
      Cochrane Library, Database of Abstracts of Reviews of Effectiveness (DARE) and
      several Ovid databases were searched for systematic reviews of interventions for
      the six behaviours (updated search 2008). Two reviewers applied the inclusion
      criteria, extracted data and assessed the quality of the reviews. The results
      were discussed in a narrative synthesis. RESULTS: We included 103 reviews
      published between 1995 and 2008. The focus of interventions varied, but those
      targeting specific individuals were generally designed to change an existing
      behaviour (e.g. cigarette smoking, alcohol misuse), whilst those aimed at the
      general population or groups such as school children were designed to promote
      positive behaviours (e.g. healthy eating). Almost 50% (n = 48) of the reviews
      focussed on smoking (either prevention or cessation). Interventions that were
      most effective across a range of health behaviours included physician advice or
      individual counselling, and workplace- and school-based activities. Mass media
      campaigns and legislative interventions also showed small to moderate effects in
      changing health behaviours.Generally, the evidence related to short-term effects
      rather than sustained/longer-term impact and there was a relative lack of
      evidence on how best to address inequalities. CONCLUSIONS: Despite limitations of
      the review of reviews approach, it is encouraging that there are interventions
      that are effective in achieving behavioural change. Further emphasis in both
      primary studies and secondary analysis (e.g. systematic reviews) should be placed
      on assessing the differential effectiveness of interventions across different
      population subgroups to ensure that health inequalities are addressed.

PMID- 20825661
TI  - A multifactorial analysis of obesity as CVD risk factor: use of neural network
      based methods in a nutrigenetics context.
AB  - BACKGROUND: Obesity is a multifactorial trait, which comprises an independent
      risk factor for cardiovascular disease (CVD). The aim of the current work is to
      study the complex etiology beneath obesity and identify genetic variations and/or
      factors related to nutrition that contribute to its variability. To this end, a
      set of more than 2300 white subjects who participated in a nutrigenetics study
      was used. For each subject a total of 63 factors describing genetic variants
      related to CVD (24 in total), gender, and nutrition (38 in total), e.g. average
      daily intake in calories and cholesterol, were measured. Each subject was
      categorized according to body mass index (BMI) as normal (BMI <= 25) or
      overweight (BMI > 25). Two artificial neural network (ANN) based methods were
      designed and used towards the analysis of the available data. These corresponded
      to i) a multi-layer feed-forward ANN combined with a parameter decreasing method
      (PDM-ANN), and ii) a multi-layer feed-forward ANN trained by a hybrid method (GA
      ANN) which combines genetic algorithms and the popular back-propagation training
      algorithm. RESULTS: PDM-ANN and GA-ANN were comparatively assessed in terms of
      their ability to identify the most important factors among the initial 63
      variables describing genetic variations, nutrition and gender, able to classify a
      subject into one of the BMI related classes: normal and overweight. The methods
      were designed and evaluated using appropriate training and testing sets provided
      by 3-fold Cross Validation (3-CV) resampling. Classification accuracy,
      sensitivity, specificity and area under receiver operating characteristics curve
      were utilized to evaluate the resulted predictive ANN models. The most
      parsimonious set of factors was obtained by the GA-ANN method and included
      gender, six genetic variations and 18 nutrition-related variables. The
      corresponding predictive model was characterized by a mean accuracy equal of
      61.46% in the 3-CV testing sets. CONCLUSIONS: The ANN based methods revealed
      factors that interactively contribute to obesity trait and provided predictive
      models with a promising generalization ability. In general, results showed that
      ANNs and their hybrids can provide useful tools for the study of complex traits
      in the context of nutrigenetics.

PMID- 20825662
TI  - Substitution of adeno-associated virus Rep protein binding and nicking sites with
      human chromosome 19 sequences.
AB  - BACKGROUND: Adeno-associated virus type 2 (AAV2) preferentially integrates its
      DNA at a ~2 kb region of human chromosome 19, designated AAVS1 (also known as
      MBS85). Integration at AAVS1 requires the AAV2 replication (Rep) proteins and a
      DNA sequence within AAVS1 containing a 16 bp Rep recognition sequence (RRS) and
      closely spaced Rep nicking site (also referred to as a terminal resolution site,
      or trs). The AAV2 genome is flanked by inverted terminal repeats (ITRs). Each ITR
      contains an RRS and closely spaced trs, but the sequences differ from those in
      AAVS1. These ITR sequences are required for replication and packaging. RESULTS:
      In this study we demonstrate that the AAVS1 RRS and trs can function in AAV2
      replication, packaging and integration by replacing a 61 bp region of the AAV2
      ITR with a 49 bp segment of AAVS1 DNA. Modifying one or both ITRs did not have a
      large effect on the overall virus titers. These modifications did not detectably
      affect integration at AAVS1, as measured by semi-quantitative nested PCR assays.
      Sequencing of integration junctions shows the joining of the modified ITRs to
      AAVS1 sequences. CONCLUSIONS: The ability of these AAVS1 sequences to substitute
      for the AAV2 RRS and trs provides indirect evidence that the stable secondary
      structure encompassing the trs is part of the AAV2 packaging signal.

PMID- 20825664
TI  - The incidence of all stroke and stroke subtype in the United Kingdom, 1985 to
      2008: a systematic review.
AB  - BACKGROUND: There is considerable geographic variation in stroke mortality around
      the United Kingdom (UK). Whether this is due to geographical differences in
      incidence or case-fatality is unclear. We conducted a systematic review of high
      quality studies documenting the incidence of any stroke and stroke subtypes,
      between 1985 and 2008 in the UK. We aimed to study geographic and temporal trends
      in relation to equivalent mortality trends. METHODS: MEDLINE and EMBASE were
      searched, reference lists inspected and authors of included papers were
      contacted. All rates were standardised to the European Standard Population for
      those over 45, and between 45 and 74 years. Stroke mortality rates for the
      included areas were then calculated to produce rate ratios of stroke mortality to
      incidence for each location. RESULTS: Five papers were included in this review.
      Geographic variation was narrow but incidence appeared to largely mirror
      mortality rates for all stroke. For men over 45, incidence (and confidence
      intervals) per 100,000 ranged from 124 (109-141) in South London, to 185 (164
      208) in Scotland. For men, premature (45-74 years) stroke incidence per 100,000
      ranged from 79 (67-94) in the North West, to 112 (95-132) in Scotland. Stroke
      subtype data was more geographically restricted, but did suggest there is no
      sizeable variation in incidence by subtype around the country. Only one paper,
      based in South London, had data on temporal trends. This showed that there has
      been a decline in stroke incidence since the mid 1990 s. This could not be
      compared to any other locations in this review. CONCLUSIONS: Geographic
      variations in stroke incidence appear to mirror variations in mortality rates.
      This suggests policies to reduce inequalities in stroke mortality should be
      directed at risk factor profiles rather than treatment after a first incident
      event. More high quality stroke incidence data from around the UK are needed
      before this can be confirmed.

PMID- 20825663
TI  - Hippocampal activity during the transverse patterning task declines with
      cognitive competence but not with age.
AB  - BACKGROUND: The hippocampus is a brain region that is particularly affected by
      age-related morphological changes. It is generally assumed that a loss in
      hippocampal volume results in functional deficits that contribute to age-related
      cognitive decline. In a combined cross-sectional behavioural and
      magnetoencephalography (MEG) study we investigated whether hippocampal-associated
      neural current flow during a transverse patterning task - which requires learning
      relational associations between stimuli - correlates with age and whether it is
      modulated by cognitive competence. RESULTS: Better performance in several tests
      of verbal memory, verbal fluency and executive function was indeed associated
      with higher hippocampal neural activity. Age, however, was not related to the
      strength of hippocampal neural activity: elderly participants responded slower
      than younger individuals but on average produced the same neural mass activity.
      CONCLUSIONS: Our results suggest that in non-pathological aging, hippocampal
      neural activity does not decrease with age but is rather related to cognitive
      competence.

PMID- 20825665
TI  - Genomic distance entrained clustering and regression modelling highlights
      interacting genomic regions contributing to proliferation in breast cancer.
AB  - BACKGROUND: Genomic copy number changes and regional alterations in epigenetic
      states have been linked to grade in breast cancer. However, the relative
      contribution of specific alterations to the pathology of different breast cancer
      subtypes remains unclear. The heterogeneity and interplay of genomic and
      epigenetic variations means that large datasets and statistical data mining
      methods are required to uncover recurrent patterns that are likely to be
      important in cancer progression. RESULTS: We employed ridge regression to model
      the relationship between regional changes in gene expression and proliferation.
      Regional features were extracted from tumour gene expression data using a novel
      clustering method, called genomic distance entrained agglomerative (GDEC)
      clustering. Using gene expression data in this way provides a simple means of
      integrating the phenotypic effects of both copy number aberrations and
      alterations in chromatin state. We show that regional metagenes derived from GDEC
      clustering are representative of recurrent regions of epigenetic regulation or
      copy number aberrations in breast cancer. Furthermore, detected patterns of
      genomic alterations are conserved across independent oestrogen receptor positive
      breast cancer datasets. Sequential competitive metagene selection was used to
      reveal the relative importance of genomic regions in predicting proliferation
      rate. The predictive model suggested additive interactions between the most
      informative regions such as 8p22-12 and 8q13-22. CONCLUSIONS: Data-mining of
      large-scale microarray gene expression datasets can reveal regional clusters of
      co-ordinate gene expression, independent of cause. By correlating these clusters
      with tumour proliferation we have identified a number of genomic regions that act
      together to promote proliferation in ER+ breast cancer. Identification of such
      regions should enable prioritisation of genomic regions for combinatorial
      functional studies to pinpoint the key genes and interactions contributing to
      tumourigenicity.

PMID- 20825666
TI  - How HIV/AIDS scale-up has impacted on non- HIV priority services in Zambia.
AB  - BACKGROUND: Much of the debate as to whether or not the scaling up of HIV service
      delivery in Africa benefits non-HIV priority services has focused on the use of
      nationally aggregated data. This paper analyses and presents routine health
      facility record data to show trend correlations across priority services.
      METHODS: Review of district office and health facility client records for 39
      health facilities in three districts of Zambia, covering four consecutive years
      (2004-07). Intra-facility analyses were conducted, service and coverage trends
      assessed and rank correlations between services measured to compare service
      trends within facilities. RESULTS: VCT, ART and PMTCT client numbers and coverage
      levels increased rapidly. There were some strong positive correlations in trends
      within facilities between reproductive health services (family planning and
      antenatal care) and ART and PMTCT, with Spearman rank correlations ranging from
      0.33 to 0.83. Childhood immunisation coverage also increased. Stock-outs of
      important drugs for non-HIV priority services were significantly more frequent
      than were stock-outs of antiretroviral drugs. CONCLUSIONS: The analysis shows
      scale-up in reproductive health service numbers in the same facilities where HIV
      services were scaling up. While district childhood immunisations increased
      overall, this did not necessarily occur in facility catchment areas where HIV
      service scale-up occurred. The paper demonstrates an approach for comparing
      correlation trends across different services, using routine health facility
      information. Larger samples and explanatory studies are needed to understand the
      client, facility and health systems factors that contribute to positive and
      negative synergies between priority services.

PMID- 20825667
TI  - What is known about the patient's experience of medical tourism? A scoping
      review.
AB  - BACKGROUND: Medical tourism is understood as travel abroad with the intention of
      obtaining non-emergency medical services. This practice is the subject of
      increasing interest, but little is known about its scope. METHODS: A
      comprehensive scoping review of published academic articles, media sources, and
      grey literature reports was performed to answer the question: what is known about
      the patient's experience of medical tourism? The review was accomplished in three
      steps: (1) identifying the question and relevant literature; (2) selecting the
      literature; (3) charting, collating, and summarizing the information. Overall
      themes were identified from this process. RESULTS: 291 sources were identified
      for review from the databases searched, the majority of which were media pieces
      (n = 176). A further 57 sources were included for review after hand searching
      reference lists. Of the 348 sources that were gathered, 216 were ultimately
      included in this scoping review. Only a small minority of sources reported on
      empirical studies that involved the collection of primary data (n = 5). The four
      themes identified via the review were: (1) decision-making (e.g., push and pull
      factors that operate to shape patients' decisions); (2) motivations (e.g.,
      procedure-, cost-, and travel-based factors motivating patients to seek care
      abroad); (3) risks (e.g., health and travel risks); and (4) first-hand accounts
      (e.g., patients' experiential accounts of having gone abroad for medical care).
      These themes represent the most discussed issues about the patient's experience
      of medical tourism in the English-language academic, media, and grey literatures.
      CONCLUSIONS: This review demonstrates the need for additional research on
      numerous issues, including: (1) understanding how multiple information sources
      are consulted and evaluated by patients before deciding upon medical tourism; (2)
      examining how patients understand the risks of care abroad; (3) gathering
      patients' prospective and retrospective accounts; and (4) the push and pull
      factors, as well as the motives of patients to participate in medical tourism.
      The findings from this scoping review and the knowledge gaps it uncovered also
      demonstrate that there is great potential for new contributions to our
      understanding of the patient's experience of medical tourism.

PMID- 20825668
TI  - Long-term effect of latanoprost/timolol fixed combination in patients with
      glaucoma or ocular hypertension: a prospective, observational, noninterventional
      study.
AB  - BACKGROUND: Prospective, observational studies that enroll large numbers of
      patients with few exclusion criteria may better reflect actual ongoing clinical
      experience than randomized clinical trials. Our purpose was to obtain efficacy
      and safety information from a cohort of subjects exposed to latanoprost/timolol
      fixed combination (FC) for >=18 months using a prospective, observational design.
      METHODS: In all, 577 office-based ophthalmologists in Germany switched 2339
      patients with glaucoma or ocular hypertension to latanoprost/timolol FC for
      medical reasons. Follow-up visits were scheduled for every 6 months over 24
      months; physicians followed usual care routines. Intraocular pressure (IOP),
      visual field status, optic nerve head findings, and adverse events were recorded.
      Efficacy parameters were evaluated for the per protocol (PP) population; the
      safety population included subjects receiving >=1 drop of FC. Physicians rated
      efficacy, tolerability, and subject compliance at month 24. RESULTS: Of the 2339
      subjects switched to latanoprost/timolol FC (safety population), the primary
      reasons for switching were inadequate IOP reduction (78.2%) and desire to
      simplify treatment with once-daily dosing (29.4%; multiple reasons possible). In
      all, 1317 (56.3%) subjects completed the study, and 1028 (44.0%) were included in
      the PP population. Most discontinuations were due to loss to follow-up. Change in
      mean IOP from baseline to month 6 was -4.0 +/- 4.31 mmHg, a reduction that was
      maintained throughout (P < 0.05 for change at all time points). By investigator
      assessments, optic disc parameters and visual field were stable over 24 months,
      and there was no relationship between IOP reduction over 24 months and
      development of a visual field defect. More than 90% of physicians rated
      latanoprost/timolol FC as "very good" or "good" for efficacy (PP population),
      tolerability, and compliance. The FC was safe and well tolerated. No change in
      iris color was reported by most subjects (83.1%) at month 24. CONCLUSIONS: Over
      24 months, latanoprost/timolol FC effectively lowers IOP levels and is well
      tolerated in patients with glaucoma or ocular hypertension who change from their
      previous ocular hypotensive therapy for medical reasons. Investigator assessments
      found optic disc parameters and visual field to be stable throughout 24 months of
      follow-up.

PMID- 20825669
TI  - Effectiveness of the universal prevention program 'Healthy School and Drugs':
      study protocol of a randomized clustered trial.
AB  - BACKGROUND: Substance use is highly prevalent among Dutch adolescents. The
      Healthy School and Drugs program is a nationally implemented school-based
      prevention program aimed at reducing early and excessive substance use among
      adolescents. Although the program's effectiveness was tested in a quasi
      experimental design before, many program changes were made afterwards. The
      present study, therefore, aims to test the effects of this widely used, renewed
      universal prevention program. METHODS/DESIGN: A randomized clustered trial will
      be conducted among 3,784 adolescents of 23 secondary schools in The Netherlands.
      The trial has three conditions; two intervention conditions (i.e., e-learning and
      integral) and a control condition. The e-learning condition consists of three
      digital learning modules (i.e., about alcohol, tobacco, and marijuana) that are
      sequentially offered over the course of three school years (i.e., grade 1, grade
      2, and grade 3). The integral condition consists of parental participation in a
      parental meeting on substance use, regulation of substance use, and monitoring
      and counseling of students' substance use at school, over and above the three
      digital modules. The control condition is characterized as business as usual.
      Participating schools were randomly assigned to either an intervention or control
      condition.Participants filled out a digital questionnaire at baseline and will
      fill out the same questionnaire three more times at follow-up measurements (8,
      20, and 32 months after baseline). Outcome variables included in the
      questionnaire are the percentage of binge drinking (more than five drinks per
      occasion), the average weekly number of drinks, and the percentage of adolescents
      who ever drunk a glass of alcohol and the percentage of adolescents who ever
      smoked a cigarette or a joint respectively for tobacco and marijuana. DISCUSSION:
      This study protocol describes the design of a randomized clustered trial that
      evaluates the effectiveness of a school-based prevention program. We expect that
      significantly fewer adolescents will engage in early or excessive substance use
      behaviors in the intervention conditions compared to the control condition as a
      direct result of the intervention. We expect that the integral condition will
      yield most positive results, compared with the e-learning condition and control
      condition. TRIAL REGISTRATION: The protocol for this study is registered with the
      Nederlands Trial Register NTR1516.

PMID- 20825670
TI  - Markedly different genome arrangements between serotype a strains and serotypes b
      or c strains of Aggregatibacter actinomycetemcomitans.
AB  - BACKGROUND: Bacterial phenotype may be profoundly affected by the physical
      arrangement of their genes in the genome. The Gram-negative species
      Aggregatibacter actinomycetemcomitans is a major etiologic agent of human
      periodontitis. Individual clonal types of A. actinomycetemcomitans may exhibit
      variable virulence and different patterns of disease association. This study
      examined the genome arrangement of A. actinomycetemcomitans using the genome
      sequences of serotypes a-c strains. The genome alignment and rearrangement were
      analyzed by the MAUVE and the GRIMM algorithms. The distribution patterns of
      genes along the leading/lagging strands were investigated. The occurrence and the
      location of repeat sequences relative to the genome rearrangement breakpoints
      were also determined. RESULTS: The genome arrangement of the serotype a strain
      D7S-1 is markedly different from the serotype b strain HK1651 or the serotype c
      strain D11S-1. Specific genome arrangements appear to be conserved among strains
      of the same serotypes. The reversal distance between D7S-1 and HK1651 by GRIMM
      analysis is also higher than the within-species comparisons of 7 randomly
      selected bacterial species. The locations of the orthologous genes are largely
      preserved between HK1651 and D11S-1 but not between D7S-1 and HK1651 (or D11S-1),
      irrespective of whether the genes are categorized as essential/nonessential or
      highly/nonhighly expressed. However, genome rearrangement did not disrupt the
      operons of the A. actinomycetemcomitans strains. A higher proportion of the
      genome in strain D7S-1 is occupied by repeat sequences than in strains HK1651 or
      D11S-1. CONCLUSION: The results suggest a significant evolutionary divergence
      between serotype a strains and serotypes b/c strains of A. actinomycetemcomitans.
      The distinct patterns of genome arrangement may suggest phenotypic differences
      between serotype a and serotypes b/c strains.

PMID- 20825671
TI  - Experimental assessment of pro-lymphangiogenic growth factors in the treatment of
      post-surgical lymphedema following lymphadenectomy.
AB  - INTRODUCTION: Lymphedema is a frequent consequence of lymph node excision during
      breast cancer surgery. Current treatment options are limited mainly to external
      compression therapies to limit edema development. We investigated previously,
      post-surgical lymphedema in a sheep model following the removal of a single lymph
      node and determined that autologous lymph node transplantation has the potential
      to reduce or prevent edema development. In this report, we examine the potential
      of lymphangiogenic therapy to restore lymphatic function and reduce post-surgical
      lymphedema. METHODS: Lymphangiogenic growth factors (vascular endothelial growth
      factor-C (VEGF-C) and angiopoitein-2 (ANG-2)) were loaded into a gel-based drug
      delivery system (HAMC; a blend of hyaluronan and methylcellulose). Drug release
      rates and lymphangiogenic signaling in target endothelial cells were assessed in
      vitro and vascular permeability biocompatibility tests were examined in vivo.
      Following, the removal of a single popliteal lymph node, HAMC with the growth
      factors was injected into the excision site. Six weeks later, lymphatic
      functionality was assessed by injecting (125)Iodoine radiolabelled bovine serum
      albumin ((125)I-BSA) into prenodal vessels and measuring its recovery in plasma.
      Circumferential leg measurements were plotted over time and areas under the
      curves used to quantify edema formation. RESULTS: The growth factors were
      released over a two-week period in vitro by diffusion from HAMC, with 50% being
      released in the first 24 hours. The system induced lymphangiogenic signaling in
      target endothelial cells, while inducing only a minimal inflammatory response in
      sheep. Removal of the node significantly reduced lymphatic functionality
      (Nodectomy 1.9 +/- 0.9, HAMC alone 1.7 +/- 0.8) compared with intact groups (3.2
      +/- 0.7). There was no significant difference between the growth factor treatment
      group (2.3 +/- 0.73) and the intact group. An increase in the number of
      regenerated lymphatic vessels at treatment sites was observed with fluoroscopy.
      Groups receiving HAMC plus growth factors displayed significantly reduced edema
      (107.4 +/- 51.3) compared with non-treated groups (nodectomy 219.8 +/- 118.7, and
      HAMC alone 162.6 +/- 141). CONCLUSIONS: Growth factor therapy has the potential
      to increase lymphatic function and reduce edema magnitude in an animal model of
      lymphedema. The application of this concept to lymphedema patients warrants
      further examination.

PMID- 20825672
TI  - The WW-HECT protein Smurf2 interacts with the Docking Protein NEDD9/HEF1 for
      Aurora A activation.
AB  - The multi-functional adaptor protein NEDD9/HEF1/Cas-L regulates cell motility,
      invasion and cell cycle progression, and plays key roles in cancer progression
      and metastasis. NEDD9 is localized to the centrosome and is required for
      activation of Aurora A kinase in mitosis. Here we demonstrate that the HECT-WW
      protein Smurf2 physically associates with NEDD9 and is required for the stability
      of NEDD9 protein. Smurf2 depletion results in a marked decrease in NEDD9 protein
      levels, by facilitating polyubiquitination and proteasomal degradation of NEDD9.
      Conversely, forced overexpression of Smurf2 results in upregulation of endogenous
      NEDD9 protein, confirming the role for Smurf2 in NEDD9 stability. Cells with
      Smurf2 depletion fail to activate Aurora A at the G2/M boundary, leading to a
      marked delay in mitotic entry. These observations suggest that the stable complex
      of Smurf2 and NEDD9 is required for timely entry into mitosis via Aurora A
      activation.

PMID- 20825673
TI  - Borna disease virus (BDV) circulating immunocomplex positivity in addicted
      patients in the Czech Republic: a prospective cohort analysis.
AB  - BACKGROUND: Borna disease virus (BDV) is an RNA virus belonging to the family
      Bornaviridae. Borna disease virus is a neurotropic virus that causes changes in
      mood, behaviour and cognition. BDV causes persistent infection of the central
      nervous system. Immune changes lead to activation of infection. Alcohol and drug
      dependence are associated with immune impairment. METHODS: We examined the
      seropositivity of BDV circulating immunocomplexes (CIC) in patients with alcohol
      and drug dependence and healthy individuals (blood donors). We examined 41
      addicted patients for the presence of BDV CIC in the serum by ELISA at the
      beginning of detoxification, and after eight weeks of abstinence. This is the
      first such study performed in patients with alcohol and drug dependence. RESULTS:
      BDV CIC positivity was detected in 36.59% of addicted patients on day 0 and in
      42.86% on day 56. The control group was 37.3% positive. However, we did not
      detect higher BDV CIC positivity in addicted patients in comparison with blood
      donors (p = 0.179). The significantly higher level of BDV CIC was associated with
      lower levels of GGT (gamma glutamyl transferase) (p = 0.027) and approached
      statistical significance with the lower age of addicted patients (p = 0.064). We
      did not find any association between BDV CIC positivity and other anamnestic and
      demographic characteristics. CONCLUSIONS: In our study addicted patients did not
      have significantly higher levels of BDV CIC than the control group. The highest
      levels of BDV CIC were detected in patients with lower levels of GGT and a lower
      age. TRIAL REGISTRATION: This study was approved by the ethical committee of the
      University Hospital Medical Faculty of Charles University in Pilsen, Czech
      Republic (registration number 303/2001).

PMID- 20825674
TI  - Uncontrolled asthma: assessing quality of life and productivity of children and
      their caregivers using a cross-sectional Internet-based survey.
AB  - BACKGROUND: Results of a national survey of asthmatic children that evaluated
      management goals established in 2004 by the National Asthma Education and
      Prevention Program (NAEPP) indicated that asthma symptom control fell short on
      nearly every goal. METHODS: An Internet-based survey was administered to adult
      caregivers of children aged 6-12 years with moderate to severe asthma. Asthma was
      categorized as uncontrolled when the caregiver reported pre-specified criteria
      for daytime symptoms, nighttime awakening, activity limitation, or rescue
      medication based on the NAEPP guidelines. Children's health-related quality of
      life (HRQOL) and caregivers' quality of life (QOL) were assessed using the Child
      Health Questionnaire Parent Form 28 (CHQ-PF28) and caregiver's work productivity
      using a modified Work Productivity and Activity Impairment Questionnaire.
      Children with uncontrolled vs. controlled asthma were compared. RESULTS: 360
      caregivers of children with uncontrolled asthma and 113 of children with
      controlled asthma completed the survey. Children with uncontrolled asthma had
      significantly lower CHQ-PF28 physical (mean 38.1 vs 49.8, uncontrolled vs
      controlled, respectively) and psychosocial (48.2 vs 53.8) summary measure scores.
      They were more likely to miss school (5.5 vs 2.2 days), arrive late or leave
      early (26.7 vs 7.1%), miss school-related activities (40.6 vs 6.2%), use a rescue
      inhaler at school (64.2 vs 31.0%), and visit the health office or school nurse
      (22.5 vs 8.8%). Caregivers of children with uncontrolled asthma reported
      significantly greater work and activity impairment and lower QOL for emotional,
      time-related and family activities. CONCLUSIONS: Poorly controlled asthma
      symptoms impair HRQOL of children, QOL of their caregivers, and productivity of
      both. Proper treatment and management to improve symptom control may reduce
      humanistic and economic burdens on asthmatic children and their caregivers.

PMID- 20825675
TI  - Molecular characterization of Histoplasma capsulatum isolated from an outbreak in
      treasure hunters Histoplasma capsulatum in treasure hunters.
AB  - BACKGROUND: In Mexico, primary pulmonary histoplasmosis is the most relevant
      clinical form of the disease. The geographical distribution of specific strains
      of Histoplasma capsulatum circulating in Mexico has not been fully established.
      Outbreaks must be reported in order to have current, updated information on this
      disease, identifying new endemic areas, manner of exposure to the fungi, and
      molecular characterization of the causative agents. We report a recent outbreak
      of histoplasmosis in treasure hunters and the molecular characterization of two
      isolates obtained from these patients. METHODS: Six patients admitted to the
      National Institute of Respiratory Diseases (INER) in Mexico City presented severe
      respiratory symptoms suggestive of histoplasmosis. They acquired the infection in
      the Veracruz (VZ) endemic zone. Diagnosis was made by X-ray and Computed
      tomography (CT), liver function, immunological techniques, and culture.
      Identification of H. capsulatum isolates was confirmed by using Polymerase chain
      reaction (PCR) was conducted with a probe from the M antigen, and the isolates
      were characterized by means of Random amplification of polymorphic DNA (RAPD)-PCR
      employed the 1253 oligonucleotide and a mixture of oligonucleotides 1281 and
      1283. These were compared to eight reference strain isolates from neighboring
      areas. RESULTS: X-ray and CT revealed disseminated micronodular images throughout
      lung parenchyma, as well as bilateral retrocaval, prevascular, subcarinal, and
      hilar adenopathies, hepatosplenomegaly, and altered liver function tests. Five of
      the six patients developed disseminated histoplasmosis. Two H. capsulatum strains
      were isolated. The same band profile was detected in both strains, indicating
      that both isolates corresponded to the sole H. capsulatum strain. Molecular
      characterization of the isolates was similar in 100% with the EH-53 Hidalgo human
      (HG) strain (reference strain integrated into the LAm A clade described for Latin
      America). CONCLUSIONS: The two isolates appeared to possess the same polymorphic
      pattern; they are indistinguishable from each other and from EH-53. It is
      important to remain updated on recent outbreaks of histoplasmosis, the manner of
      exposure to the fungi, as well as the molecular characterization of the isolates.
      The severity of cases indicates that this strain is highly virulent and that it
      is probably prevalent in Hidalgo and Veracruz states.

PMID- 20825676
TI  - Is the use of sentient animals in basic research justifiable?
AB  - Animals can be used in many ways in science and scientific research. Given that
      society values sentient animals and that basic research is not goal oriented, the
      question is raised: "Is the use of sentient animals in basic research
      justifiable?" We explore this in the context of funding issues, outcomes from
      basic research, and the position of society as a whole on using sentient animals
      in research that is not goal oriented. We conclude that the use of sentient
      animals in basic research cannot be justified in light of society's priorities.

PMID- 20825677
TI  - Mobile learning for HIV/AIDS healthcare worker training in resource-limited
      settings.
AB  - BACKGROUND: We present an innovative approach to healthcare worker (HCW) training
      using mobile phones as a personal learning environment.Twenty physicians used
      individual Smartphones (Nokia N95 and iPhone), each equipped with a portable
      solar charger. Doctors worked in urban and peri-urban HIV/AIDS clinics in Peru,
      where almost 70% of the nation's HIV patients in need are on treatment. A set of
      3D learning scenarios simulating interactive clinical cases was developed and
      adapted to the Smartphones for a continuing medical education program lasting 3
      months. A mobile educational platform supporting learning events tracked
      participant learning progress. A discussion forum accessible via mobile connected
      participants to a group of HIV specialists available for back-up of the medical
      information. Learning outcomes were verified through mobile quizzes using
      multiple choice questions at the end of each module. METHODS: In December 2009, a
      mid-term evaluation was conducted, targeting both technical feasibility and user
      satisfaction. It also highlighted user perception of the program and the
      technical challenges encountered using mobile devices for lifelong learning.
      RESULTS: With a response rate of 90% (18/20 questionnaires returned), the overall
      satisfaction of using mobile tools was generally greater for the iPhone. Access
      to Skype and Facebook, screen/keyboard size, and image quality were cited as more
      troublesome for the Nokia N95 compared to the iPhone. CONCLUSIONS: Training,
      supervision and clinical mentoring of health workers are the cornerstone of the
      scaling up process of HIV/AIDS care in resource-limited settings (RLSs).
      Educational modules on mobile phones can give flexibility to HCWs for accessing
      learning content anywhere. However lack of softwares interoperability and the
      high investment cost for the Smartphones' purchase could represent a limitation
      to the wide spread use of such kind mLearning programs in RLSs.

PMID- 20825678
TI  - Mitochondrial genotype in vulvar carcinoma - cuckoo in the nest.
AB  - Vulvar squamous cell carcinoma (VSCC) is a rare female genital neoplasm. Although
      numerous molecular changes have been reported in VSCC, biomarkers of clinical
      relevance are still lacking. On the other hand, there is emerging evidence on the
      use of mtDNA as a diagnostic tool in oncology. In order to investigate mtDNA
      status in VSCC patients, haplogroup distribution analysis and D-loop sequencing
      were performed. The results were compared with available data for the general
      Polish population, cancer free-centenarians as well as patients with endometrial
      and head and neck cancer. The obtained data were also compared with the current
      status of mitochondrial databases. Significant differences in haplogroup
      distribution between VSCC cohort, general Polish population and cancer-free
      centenarians cohort were found. Moreover, a correlation between the VSCC patients
      haplogroup and HPV status was observed. Finally, a specific pattern of mtDNA
      polymorphisms was found in VSCC. Our results suggest that the mitochondrial
      genetic background may influence the risk of VSCC occurrence as well as
      susceptibility to HPV infection.

PMID- 20825679
TI  - Safety standards and socioeconomic disparities in school playground injuries: a
      retrospective cohort study.
AB  - BACKGROUND: Playground injuries are fairly common and can require hospitalization
      and or surgery. Previous research has suggested that compliance with guidelines
      or standards can reduce the incidence of such injuries, and that poorer children
      are at increased risk of playground injuries. OBJECTIVE: The objective of this
      study was to determine the association between playground injury and school
      socioeconomic status before and after the upgrading of playground equipment to
      meet CSA guidelines. METHODS: Injury data were collected from January 1998
      December 1999 and January 2004 - June 2007 for 374 elementary schools in Toronto,
      Canada. The objective of this study was to investigate the effect of a program of
      playground assessment, upgrading, and replacement on school injury rates and
      socio-economic status. Injury rates were calculated for all injuries, injuries
      that did not occur on equipment, and injuries on play equipment. Poisson
      regression was performed to determine the relationship between injury rates and
      school socio-economic status. RESULTS: Prior to upgrading the equipment there was
      a significant relationship between socio-economic status and equipment-related
      injuries with children at poorer schools being at increased risk (Relative risk:
      1.52 [95% CI = 1.24-1.86]). After unsafe equipment was upgraded, the relationship
      between injury and SES decreased and was no longer significant (RR 1.13 [95% CI =
      0.95-1.32]). CONCLUSIONS: Improvements in playground equipment can result in an
      environment in which students from schools in poorer neighbourhoods are no longer
      at increased risk of injuries on play equipment.

PMID- 20825680
TI  - Effects of F/G-actin ratio and actin turn-over rate on NADPH oxidase activity in
      microglia.
AB  - BACKGROUND: Most in vivo studies that have addressed the role of actin dynamics
      in NADPH oxidase function in phagocytes have used toxins to modulate the
      polymerization state of actin and mostly effects on actin has been evaluated by
      end point measurements of filamentous actin, which says little about actin
      dynamics, and without consideration for the subcellular distribution of the
      perturbed actin cytoskeleton. RESULTS: Here, we in addition to toxins use
      conditional expression of the major actin regulatory protein LIM kinase-1
      (LIMK1), and shRNA knock-down of cofilin to modulate the cellular F/G-actin ratio
      in the Ra2 microglia cell line, and we use Fluorescence Recovery after
      Photobleaching (FRAP) in beta-actin-YFP-transduced cells to obtain a dynamic
      measure of actin recovery rates (actin turn-over rates) in different F/G-actin
      states of the actin cytoskeleton. Our data demonstrate that stimulated NADPH
      oxidase function was severely impaired only at extreme actin recovery rates and
      F/G-actin ratios, and surprisingly, that any moderate changes of these parameters
      of the actin cytoskeleton invariably resulted in an increased NADPH oxidase
      activity. CONCLUSION: moderate actin polymerization and depolymerization both
      increase the FMLP and PMA-stimulated NADPH oxidase activity of microglia, which
      is directly correlated with neither actin recovery rate nor F/G- actin ratio. Our
      results indicate that NADPH oxidase functions in an enhanced state of activity in
      stimulated phagocytes despite widely different states of the actin cytoskeleton.

PMID- 20825681
TI  - Selecting instruments for assessing psychological wellbeing in Afghan and Kurdish
      refugee groups.
AB  - BACKGROUND: Afghan and Iraqi refugees comprise nearly half of all those currently
      under United Nations protection. As many of them will eventually be resettled in
      countries outside the region of origin, their long term health and settlement
      concerns are of relevance to host societies, and will be a likely focus for
      future research. Since Australia and New Zealand have both accepted refugees for
      many years and have dedicated, but different settlement and immigration policies,
      a study comparing the resettlement of two different refugee groups in these
      countries was undertaken. The purpose of this article is to describe the
      instrument selection for this study assessing mental health and psychological
      well being with Afghan and Kurdish former refugees, in particular to address
      linguistic considerations and translated instrument availability. A summary of
      instruments previously used with refugee and migrant groups from the Middle East
      region is presented to assist other researchers, before describing the three
      instruments ultimately selected for the quantitative component of our study.
      FINDINGS: The Kessler-10 Psychological Distress Scale (K10), General Perceived
      Self-Efficacy Scale (GPSE), and Personal Well-Being Index (PWI) all showed good
      reliability (Cronbach's alphas of 0.86, 0.89 and 0.83 respectively for combined
      language versions) and ease of use even for pre-literate participants, with the
      sample of 193 refugees, although some concepts in the GPSE proved problematic for
      a small number of respondents. Farsi was the language of choice for the majority
      of Afghan participants, while most of the Kurds chose to complete English
      versions in addition to Farsi. No one used Arabic or Turkish translations.
      Participants settled less than ten years were more likely to complete
      questionnaires in Farsi. Descriptive summary statistics are presented for each
      instrument with results split by gender, refugee group and language version
      completed. CONCLUSION: This paper discusses instrument selection for Farsi and
      Arabic speaking refugee participants from the Middle East and Afghanistan,
      concluding that the Kessler-10, GPSE scale and PWI were suitable for use with
      these groups. Suitable language translations are freely available. Our experience
      with these instruments may help inform other studies with these vulnerable
      groups.

PMID- 20825682
TI  - Correlates of sedentary behaviours in preschool children: a review.
AB  - BACKGROUND: Sedentary behaviour has been linked with a number of health outcomes.
      Preschool-aged children spend significant proportions of their day engaged in
      sedentary behaviours. Research into the correlates of sedentary behaviours in the
      preschool population is an emerging field, with most research being published
      since 2002. Reviews on correlates of sedentary behaviours which include preschool
      children have previously been published; however, none have reported results
      specific to the preschool population. This paper reviews articles reporting on
      correlates of sedentary behaviour in preschool children published between 1993
      and 2009. METHODS: A literature search was undertaken to identify articles which
      examined correlates of sedentary behaviours in preschool children. Articles were
      retrieved and evaluated in 2008 and 2009. RESULTS: Twenty-nine studies were
      identified which met the inclusion criteria. From those studies, 63 potential
      correlates were identified. Television viewing was the most commonly examined
      sedentary behaviour. Findings from the review suggest that child's sex was not
      associated with television viewing and had an indeterminate association with
      sedentary behaviour as measured by accelerometry. Age, body mass index, parental
      education and race had an indeterminate association with television viewing, and
      outdoor playtime had no association with television viewing. The remaining 57
      potential correlates had been investigated too infrequently to be able to draw
      robust conclusions about associations. CONCLUSIONS: The correlates of preschool
      children's sedentary behaviours are multi-dimensional and not well established.
      Further research is required to provide a more comprehensive understanding of the
      influences on preschool children's sedentary behaviours to better inform the
      development of interventions.

PMID- 20825683
TI  - Prevention of post-surgical abdominal adhesions by a novel biodegradable
      thermosensitive PECE hydrogel.
AB  - BACKGROUND: Post-operative peritoneal adhesions are common and serious
      complications for modern medicine. We aim to prevent post-surgical adhesions
      using biodegradable and thermosensitive poly(ethylene glycol)-poly(epsilon
      caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel. In this work,
      we investigated the effect of PECE hydrogel on preventing post-surgical abdominal
      adhesions in mouse and rat models. RESULTS: The PECE hydrogel in sol state could
      be transformed into gel in less than 20 s at 37 degrees C. In addition, the PECE
      hydrogel could be easily adhered to the damaged peritoneal surfaces, and be
      gradually degraded and absorbed by the body within 14 days along with the healing
      of peritoneal wounds. A notable efficacy of the PECE hydrogel in preventing
      peritoneal adhesions was demonstrated in the animal models. In contrast, all
      untreated animals developed adhesions requiring sharp dissection. Furthermore, no
      significant histopathological changes were observed in main organs of the
      hydrogel-treated animals. CONCLUSION: Our results suggested that the
      thermosensitive PECE hydrogel was an effective, safe, and convenient agent on
      preventing post-surgical intro-abdominal adhesions.

PMID- 20825684
TI  - On the choice and number of microarrays for transcriptional regulatory network
      inference.
AB  - BACKGROUND: Transcriptional regulatory network inference (TRNI) from large
      compendia of DNA microarrays has become a fundamental approach for discovering
      transcription factor (TF)-gene interactions at the genome-wide level. In
      correlation-based TRNI, network edges can in principle be evaluated using
      standard statistical tests. However, while such tests nominally assume
      independent microarray experiments, we expect dependency between the experiments
      in microarray compendia, due to both project-specific factors (e.g., microarray
      preparation, environmental effects) in the multi-project compendium setting and
      effective dependency induced by gene-gene correlations. Herein, we characterize
      the nature of dependency in an Escherichia coli microarray compendium and explore
      its consequences on the problem of determining which and how many arrays to use
      in correlation-based TRNI. RESULTS: We present evidence of substantial effective
      dependency among microarrays in this compendium, and characterize that dependency
      with respect to experimental condition factors. We then introduce a measure neff
      of the effective number of experiments in a compendium, and find that
      corresponding to the dependency observed in this particular compendium there is a
      huge reduction in effective sample size i.e., neff = 14.7 versus n = 376.
      Furthermore, we found that the neff of select subsets of experiments actually
      exceeded neff of the full compendium, suggesting that the adage 'less is more'
      applies here. Consistent with this latter result, we observed improved
      performance in TRNI using subsets of the data compared to results using the full
      compendium. We identified experimental condition factors that trend with changes
      in TRNI performance and neff , including growth phase and media type. Finally,
      using the set of known E. coli genetic regulatory interactions from RegulonDB, we
      demonstrated that false discovery rates (FDR) derived from neff -adjusted p
      values were well-matched to FDR based on the RegulonDB truth set. CONCLUSIONS:
      These results support utilization of neff as a potent descriptor of microarray
      compendia. In addition, they highlight a straightforward correlation-based method
      for TRNI with demonstrated meaningful statistical testing for significant edges,
      readily applicable to compendia from any species, even when a truth set is not
      available. This work facilitates a more refined approach to construction and
      utilization of mRNA expression compendia in TRNI.

PMID- 20825685
TI  - A nested leucine rich repeat (LRR) domain: the precursor of LRRs is a ten or
      eleven residue motif.
AB  - BACKGROUND: Leucine rich repeats (LRRs) are present in over 60,000 proteins that
      have been identified in viruses, bacteria, archae, and eukaryotes. All known
      structures of repeated LRRs adopt an arc shape. Most LRRs are 20-30 residues
      long. All LRRs contain LxxLxLxxNxL, in which "L" is Leu, Ile, Val, or Phe and "N"
      is Asn, Thr, Ser, or Cys and "x" is any amino acid. Seven classes of LRRs have
      been identified. However, other LRR classes remains to be characterized. The
      evolution of LRRs is not well understood. RESULTS: Here we describe a novel LRR
      domain, or nested repeat observed in 134 proteins from 54 bacterial species. This
      novel LRR domain has 21 residues with the consensus sequence of
      LxxLxLxxNxLxxLDLxx(N/L/Q/x)xx or LxxLxCxxNxLxxLDLxx(N/L/x)xx. This LRR domain is
      characterized by a nested periodicity; it consists of alternating 10- and 11-
      residues units of LxxLxLxxNx(x/-). We call it "IRREKO" LRR, since the Japanese
      word for "nested" is "IRREKO". The first unit of the "IRREKO" LRR domain is
      frequently occupied by an "SDS22-like" LRR with the consensus of
      LxxLxLxxNxLxxLxxLxxLxx or a "Bacterial" LRR with the consensus of
      LxxLxLxxNxLxxLPxLPxx. In some proteins an "SDS22-like" LRR intervenes between
      "IRREKO" LRRs. CONCLUSION: Proteins having "IRREKO" LRR domain are almost
      exclusively found in bacteria. It is suggested that IRREKO@LRR evolved from a
      common ancestor with "SDS22-like" and "Bacterial" classes and that the ancestor
      of IRREKO@LRR is 10 or 11 residues of LxxLxLxxNx(x/-). The "IRREKO" LRR is
      predicted to adopt an arc shape with smaller curvature in which beta-strands are
      formed on both concave and convex surfaces.

PMID- 20825686
TI  - Sepsis induced changes of adipokines and cytokines - septic patients compared to
      morbidly obese patients.
AB  - BACKGROUND: Hyperglycemia and insulin resistance frequently occur in critically
      ill and in morbidly obese (MO) patients. Both conditions are associated with
      altered serum levels of cytokines and adipokines. In addition, obesity related
      alterations in adipokine expression contribute to insulin resistance in metabolic
      syndrome. In this study we examined the serum adipocytokine profile in critically
      ill patients, MO patients, and healthy blood donors. METHODS: 33 patients who
      fulfilled the clinical criteria for severe sepsis or septic shock (SP) were
      prospectively enrolled in this study. A multiplex analysis was performed to
      evaluate plasma levels of adiponectin, resistin, leptin, active PAI-1, MCP-1, IL
      1 alpha, IL-6, IL-8, IL-10, and TNF-alpha in 33 critically ill patients, 37 MO
      patients and 60 healthy blood donors (BD). RESULTS: In SP, adiponectin was
      significantly lowered and resistin, active PAI-1, MCP-1, IL-1 alpha, IL-6, IL-8,
      IL-10, and TNF-alpha were significantly elevated compared to BD. Leptin levels
      were unchanged. In MO, adiponectin and IL-8 were significantly lowered, leptin,
      active PAI-1, MCP-1, IL-1 alpha, IL-6, and IL-10 significantly elevated, whereas
      resistin was unaltered. In SP, adiponectin correlated negatively with BMI, SAPS
      II and SOFA scores, while resistin correlated positively with SAPS II and SOFA
      scores and leptin correlated positively with the BMI. Adiponectin was
      approximately equally diminished in SP and MO compared to BD. With the exception
      of active PAI-1, cytokine levels in SP were clearly higher compared to MO.
      CONCLUSION: A comparable adipocytokine profile was determined in critically ill
      and MO patients. As in MO, SP showed reduced adiponectin levels and elevated MCP
      1, active PAI-1, IL-1 alpha, IL-6, and IL-10 levels. Leptin is only elevated in
      MO, while resistin, IL-8, and TNF-alpha is only elevated in SP. As in MO
      patients, increased levels of proinflammatory cytokines and altered levels of
      adipokines may contribute to the development of insulin resistance in critically
      ill patients.

PMID- 20825687
TI  - Clinical correlates of arterial lactate levels in patients with ST-segment
      elevation myocardial infarction at admission: a descriptive study.
AB  - INTRODUCTION: Blood lactate measurements can be used as an indicator of
      hemodynamic impairment and relate to mortality in various forms of shock. Little
      is known at the moment concerning the clinical correlates of systemic lactate in
      patients with ST-segment elevation myocardial infarction (STEMI). METHODS: To
      assess the relation of systemic arterial lactate levels in STEMI patients with
      clinical correlates at presentation in the catheterization laboratory, we
      measured arterial lactate levels with a rapid point-of-care technique,
      immediately following femoral sheath insertion. The study population (n = 1,176)
      was divided into tertiles with lactate levels <= 1.1 (n = 410), 1.2 to 1.7 (n =
      398) and >= 1.8 mmol/l (n = 368). We compared both baseline characteristics and
      outcome measures of the three lactate groups. RESULTS: Factors independently
      associated with higher lactate levels were hypotension, heart rate, thrombolysis
      in myocardial infarction (TIMI) flow 0 to 1, diabetes and non-smoking. Mortality
      at 30 days in the three groups was 2.0%, 1.5% and 6.5%. The latter group also
      showed lower blush grades and greater enzymatic infarct sizes. An intra aortic
      balloon pump (IABP) was used more frequently in patients with higher lactate
      levels (4.2%, 7.6% and 14.7%). CONCLUSIONS: In STEMI patients, impaired
      hemodynamics, worse TIMI flow and non-smoking were related to increased arterial
      lactate levels. Higher lactate levels were independently related with 30-day
      mortality and an overall worse response to percutaneous coronary intervention
      (PCI). In particular, acute mortality was related to admission lactates >= 1.8
      mmol/L. Point-of-care measurement of arterial lactate at admission in patients
      with STEMI has the potential to improve acute risk stratification.

PMID- 20825688
TI  - Trypanorhynch cestodes of teleost fish from the Persian Gulf, Iran.
AB  - A total of 299 fish belonging to ten teleost species were studied in Iranian
      waters at the north-eastern coast of the Persian Gulf for larval trypanorhynch
      cestode infection. The following trypanorhynch species were identified:
      Callitetrarhynchus gracilis Pintner, 1931, Pseudogilquinia thomasi (Palm, 2000),
      Pterobothrium lesteri Campbell and Beveridge, 1996 and Pseudolacistorhynchus
      shipleyi (Southwell, 1929). The most abundant parasite was C. gracilis which was
      isolated from seven teleost species. The highest prevalence (62.9%) and dominance
      (0.98) were demonstrated for P. thomasi with a maximum intensity of 22 in Indian
      halibut Psettodes erumei. Collections of P. lesteri and P. shipleyi from the
      Persian Gulf represent new locality records, thus extending the known range of
      distribution for both species. Four new host records are established. The
      recorded combination of trypanorhynch species and the established host range
      correspond to other regions, such as off the Brazilian coast. In terms of species
      distribution, the north-western part of the Indian Ocean, together with the Gulf
      of Bengal and the Indonesian archipelago, share the same species, resulting from
      connected water bodies. All trypanorhynch species were isolated from the body
      cavity, except for P. thomasi which was recorded from the musculature of P.
      erumei. Relatively high intensities of infection in P. erumei may be of public
      health concern in the region, necessitating the consumption of well-cooked fish
      products.

PMID- 20825690
TI  - Molecular characterization of Cystoisospora belli and unizoite tissue cyst in
      patients with Acquired Immunodeficiency Syndrome.
AB  - Cystoisospora belli is a coccidian protozoan that can cause chronic diarrhoea,
      acalculous cholecystitis and cholangiopathy in AIDS patients. We applied
      molecular methods to identify Cystoisospora at species level in AIDS patients
      presenting with and without the presence of unizoites in lamina propria.
      Coprological and histological analyses were performed in stool and/or biopsy
      samples from 8 Cystoisospora-infected patients. DNA from the same samples was
      used to amplify 2 fragments of the SSU-rRNA gene and the ITS-1 region. Sequencing
      of the resulting amplicons identified C. belli infections in all cases,
      independent of the presence or absence of unizoite tissue cysts. Further work
      should be considered in order to find molecular targets related to strain
      variations in C. belli.

PMID- 20825689
TI  - Anthelmintic resistance: markers for resistance, or susceptibility?
AB  - The Consortium for Anthelmintic Resistance and Susceptibility (CARS) brings
      together researchers worldwide, with a focus of advancing knowledge of resistance
      and providing information on detection methods and treatment strategies. Advances
      in this field suggest mechanisms and features of resistance that are shared among
      different classes of anthelmintic. Benzimidazole resistance is characterized by
      specific amino acid substitutions in beta-tubulin. If present, these
      substitutions increase in frequency upon drug treatment and lead to treatment
      failure. In the laboratory, sequence substitutions in ion-channels can contribute
      to macrocyclic lactone resistance, but there is little evidence that they are
      significant in the field. Changes in gene expression are associated with
      resistance to several different classes of anthelmintic. Increased P-glycoprotein
      expression may prevent drug access to its site of action. Decreased expression of
      ion-channel subunits and the loss of specific receptors may remove the drug
      target. Tools for the identification and genetic analysis of parasitic nematodes
      and a new online database will help to coordinate research efforts in this area.
      Resistance may result from a loss of sensitivity as well as the appearance of
      resistance. A focus on the presence of anthelmintic susceptibility may be as
      important as the detection of resistance.

PMID- 20825691
TI  - Weight status and determinants of health in Manitoba children and youth.
AB  - PURPOSE: Because of the tremendous increase in overweight and obesity in Canadian
      children and youth in recent decades, we examined associations among health
      determinants, healthy living characteristics, and overweight and obesity in
      Manitoba children and youth. METHODS: Using descriptive statistics and logistic
      regression, we identified factors associated with measured overweight and obesity
      in a sample of 1651 Manitoba children and youth aged two to 17 years from the
      2004 Canadian Community Health Survey 2.2-Nutrition. RESULTS: Thirty-one percent
      of the children and youth were overweight or obese. Males aged 12 to 17 or from
      food-insecure homes were more likely to be overweight or obese than were younger
      males or males from food-secure households. Females from households with higher
      parental education were less likely to be overweight or obese than were those
      from households with lower parental education. Female youth who were sedentary
      for at least three hours daily were more likely to be overweight or obese than
      were less sedentary female youth. A trend toward significance with overweight or
      obesity in youth was noted with levels of daily fruit and vegetable consumption
      and regular physical activity. CONCLUSIONS: Overweight and obesity in Manitoba
      children and youth are associated with socio-economic and demographic
      characteristics, and with food and activity behaviours. These findings can inform
      health and nutrition policy and practice by indicating health inequities that
      require particular attention.

PMID- 20825692
TI  - Body image and dieting attitudes among preadolescents.
AB  - PURPOSE: Differences in body image and dieting concerns were assessed in
      preadolescent boys and girls across the body mass index (BMI) spectrum. The
      hypothesis was that girls would express more concern with body size, report more
      dieting, and receive more advice than boys. METHODS: In this cross-sectional
      descriptive study, age-appropriate figure drawings, the Children's Eating
      Attitudes Test (ChEAT), the Restraint Scale, and the Body Esteem Scale were
      administered to participants in the Study of Asthma, Genes and Environment,
      Manitoba. Responses were compared between genders and correlated with BMI
      percentiles. RESULTS: A total of 565 10- and 11-year-old children (321 boys)
      completed questionnaires. Overall, 39% of participants wanted to be thinner, and
      no significant gender differences based on weight were found. However, the use of
      figure drawings indicated that girls desired greater changes in body size
      (p=0.006). Girls had higher Restraint Scale scores (p=0.003), but no
      statistically significant differences were found in self-reported dieting, ChEAT,
      or Body Esteem Scale scores. Approximately 25% of children reported receiving
      frequent weight-related advice. Girls did not report this more often than did
      boys. Children in the lowest BMI percentile desired the greatest change in body
      shape and had the highest Restraint Scale scores. CONCLUSIONS: Key gender
      differences underline the importance of understanding children's attitudes toward
      body image, weight, and dieting.

PMID- 20825693
TI  - Innu food consumption patterns: traditional food and body mass index.
AB  - PURPOSE: Food consumption patterns of an Innu community were described and the
      benefits of traditional food (TF) were investigated in relation to body mass
      index (BMI). METHODS: A cross-sectional study was conducted using food frequency
      and 24-hour recall questionnaires to evaluate consumption patterns (n=118) and to
      assess energy and nutrient intakes from TF and store-bought food (SBF) (n=161).
      Body mass index was calculated with a sub-sample of 45 participants. RESULTS:
      Mean yearly TF meal consumption was significantly related to age (p=0.05).
      Participants reporting high TF and low SBF consumption presented with a normal
      body weight (BMI=24.1) at the lower quartile and a slightly overweight status
      (BMI=25.8) at the median. Mean values for protein and carbohydrate intake were
      higher than the Dietary Reference Intakes, whereas dietary fibre intake was below
      these guidelines for both genders. Store-bought food provided higher levels of
      energy and nutrients, except for protein. CONCLUSIONS: Although Innu consume high
      amounts of TF and SBF, a lack of some essential nutrients was observed. Because
      TF intake was related to a tendency toward a lower BMI, a combined, targeted diet
      could be proposed. Health services could reinforce the importance of TF
      consumption and promote traditional dietary practices that offer advantages at
      many levels.

PMID- 20825694
TI  - Food purchasing and food insecurity among low-income families in Toronto.
AB  - PURPOSE: Factors underlying food-purchasing decisions were examined among a
      sample of low-income Toronto families. METHODS: A cross-sectional survey was
      completed among 485 families residing in high-poverty Toronto neighbourhoods.
      Food-security status was assessed using the Household Food Security Survey
      Module. Open-ended questions were included to examine respondents' food selection
      and management practices and their purchasing decisions for six indicator foods.
      Logistic regression was used to examine associations between factors influencing
      food-purchasing decisions, perceived food adequacy, and severity of food
      insecurity. RESULTS: Twenty-two percent of families had been severely food
      insecure in the past 30 days. Respondents engaged in thrifty food shopping
      practices, such as frequenting discount supermarkets and budgeting carefully.
      Price was the most salient factor influencing food-purchasing decisions; the
      likelihood that families would report this factor increased with deteriorating
      food security. Preference, quality, and health considerations also guided food
      purchasing decisions, but generally to a lesser extent as food insecurity
      increased. Household food supplies reflected constraints on food purchasing, and
      they diminished with increasing food insecurity. CONCLUSIONS: Despite their
      resourcefulness, low-income families struggle to feed their families. Dietitians
      have an important role to play as advocates for adequate income supports to
      promote food security and nutritional health.

PMID- 20825695
TI  - Determining knowledge and behaviour change after nutrition screening among older
      adults.
AB  - Two education interventions involving personalized messages after nutrition
      screening in older adults were compared to determine changes in nutrition
      knowledge and risk behaviour. Of 150 older adults randomly selected from a local
      seniors' centre, 61 completed baseline screening and a demographic and nutrition
      knowledge questionnaire and were randomized to one of two groups. Group A
      received personalized letters plus an educational booklet, and Group B received
      personalized letters only. All materials were sent through the mail. Forty-four
      participants completed post-test questionnaires to determine change in knowledge
      and risk behaviour. Both groups had reduced nutrition risk scores and increased
      knowledge scores at post-test. After the intervention, a significant difference
      was observed in knowledge change by treatment group. Group A participants
      experienced greater gains in knowledge, with a mean gain of 5.43 points, than did
      those in Group B, who had a mean gain of 1.36 points (p=0.018). Screening and
      education with print materials have the potential to change risk behaviour and
      nutrition knowledge in older adults. A specially designed booklet on older
      adults' nutrition risk factors plus a personalized letter provide an effective
      education strategy for older adults after screening.

PMID- 20825696
TI  - Desired skills and attributes for dietitian preceptors.
AB  - We examined the research literature to determine the skills and attributes that
      dietetic interns desire in clinical preceptors. A search of three databases
      produced little information specific to dietetics. Literature on preceptors in
      other health disciplines identified preceptor attributes that students in
      clinical placements value. We were able to cluster the data from these studies
      into four themes: knowledge and experience, personal characteristics, teaching
      skills and attitudes, and interpersonal relationships. This review suggests a
      need for further development of dietitian preceptor training, as well as for
      further research specific to dietetic interns' needs.

PMID- 20825697
TI  - Food, cooking skills, and health: a literature review.
AB  - Over the past century, a major shift in North American food practices has been
      taking place. However, the literature on this topic is lacking in several areas.
      Some available research on food and cooking practices in the current context is
      presented, with a focus on how these are affecting health and how they might be
      contributing to health inequalities within the population. First, cooking and
      cooking skills are examined, along with the ambiguities related to terms
      associated with cooking in the research literature. Food choice, cooking, and
      health are described, particularly in relation to economic factors that may lead
      to health inequalities within the population. The importance of developing an
      understanding of factors within the wider food system as part of food choice and
      cooking skills is presented, and gaps in the research literature are examined and
      areas for future research are presented. Cooking practices are not well studied
      but are important to an understanding of human nutritional health as it relates
      to cultural, environmental, and economic factors.

PMID- 20825698
TI  - Dice, golf balls, and CDs: assumptions about portion size measurement aids.
AB  - PURPOSE: Portion size measurement aids (PSMAs) are used extensively by
      dietitians. In this cross-sectional, descriptive study, we explored the degree of
      consistency and concordance between measured and putative volumes of selected
      household and sport-related PSMAs that are commonly used for nutrition education
      and dietary assessment. METHODS: An online search of portion size resources
      yielded several governmental and academic descriptions of household PMSAs (e.g.,
      a compact disc, a nine-volt battery) and sport-related PMSAs (e.g., a golf ball)
      and their purported dimensions. The spherical items were purchased locally and
      measured using electronic digital calipers; measurements were then converted to
      volumes, in millilitres. RESULTS: Overall, we observed a high degree of
      heterogeneity in how different educational resources related sport-related PSMAs
      to portion sizes of food. The mean percentage of error between the measured and
      putative volumes of PSMAs varied considerably. CONCLUSIONS: Our findings indicate
      that the inaccurate use of PSMAs can lead to systematic bias in nutrition
      education and misreporting of dietary intake during dietary assessment.
      Dietitians should exercise caution when using PSMAs because these may not reflect
      the true portion size they are meant to represent.

PMID- 20825699
TI  - Exploring adolescents' awareness of diabetes using the free association
      technique.
AB  - PURPOSE: Healthy adolescents' awareness of diabetes was explored, and gender and
      grade-level differences in understanding were determined. METHODS: Adolescents
      without diabetes in grades five, eight, and 10 (n=128) at four New Brunswick
      schools wrote down all words/expressions that came to mind when they heard the
      word "diabetes" (i.e., they used the free association technique). Answers were
      classified into categories using content analysis. RESULTS: Eighty-eight girls
      and 40 boys completed the activity (n=44, 52, and 32 in grades five, eight, and
      10, respectively). Nine principal categories were identified: 66% of the
      adolescents cited sugar (e.g., eating too much sugar, not enough sugar), 48%
      treatment (e.g., needles, injections), 45% the nature of diabetes (e.g., a
      disease, types of diabetes, heredity), 41% nutrition (e.g., diet, sugar
      containing foods, other foods), 38% blood (e.g., too much/not enough sugar in
      blood), 18% complications (e.g., death), 11% physiological
      manifestations/symptoms (e.g., fainting), 6% obesity, and 6% physical activity.
      No differences were found in category citation frequency between boys and girls
      and grade levels, except that grade 10 students more frequently cited the
      categories of treatment, blood, and obesity (p=0.05). CONCLUSIONS: Students
      thought of diabetes in terms of sugar and injections. Words related to obesity,
      prevention, and complications were cited infrequently.

PMID- 20825700
TI  - Coming full circle: reflections on a career as a dietitian.
AB  - The connections between people, careers, events, and decisions provide the focus
      for this lecture, which traces the story of a 38-year career as a dietitian,
      spanning the country from east to west, through the centre, and back again. The
      lecture emphasizes the importance of taking inspiration from family and events,
      developing and maintaining lifelong friendships, and commitments. Finding
      opportunity in the midst of adversity is also a theme. The author's career begins
      with a clinical and administrative experience and moves into the community when
      she becomes a public health nutritionist. While the budget restrictions of the
      1990s were challenging, the author recounts opportunities with key issues such as
      folic acid, prenatal nutrition, and heart health. A provincial food and nutrition
      plan was created, including a focus on food security and its connection to
      poverty. This is linked to the roots of the dietetic profession with the Lillian
      Massey School of Household Science and Art established in the 1890s. As the
      author recounts her journey, dietitians are reminded that working with partners
      and other disciplines provides the foundation for success and will be needed as
      we address the current issue of obesity.

PMID- 20825702
TI  - Unusual presentation of an uncommon abdominal pathology.
AB  - Desmoid tumour is a non-encapsulated locally invasive tumour, originating from
      fibroblasts, which has ubiquitous distribution in the body. It has a high
      tendency for local recurrence, causing deformity in the adjacent organ and
      consequent organ dysfunction. A case of a 75-year-old man, presenting with high
      grade fever, dull aching abdominal pain and weight loss, suspected to be due to
      malignancy, is reported. Contrast-enhanced computed tomography (CECT) showed a
      mass in the transverse colon with pericolic collection raising a suspicion of
      perforation. He underwent a two-stage procedure in the form of defunctioning
      ileostomy in the initial setting followed by colonic resection and anastomosis 6
      weeks later. Histological analysis revealed mesenteric fibromatosis (desmoid
      tumour). The patient was completely asymptomatic one year after surgery. We
      report this case, as our patient had none of the predisposing factors. To the
      best of our knowledge, this is the first case on colonic perforation secondary to
      desmoid tumour.

PMID- 20825703
TI  - Surgery for retroperitoneal soft tissue sarcomas: aggressive re-resection of
      recurrent disease is possible.
AB  - INTRODUCTION: Retroperitoneal soft tissue sarcomas represent a relatively rare
      and complex therapeutic problem where surgery forms the mainstay of treatment and
      is technically demanding. In this study, we review a single UK centre's
      experience with the surgical management of retro-peritoneal soft tissue sarcoma.
      PATIENTS AND METHODS: We present analysis of data on patients treated between
      1997 and 2006, our first 75 patients. Data collected from the Access database,
      included patient demographics, staging modalities, peri-operative details,
      treatment, outcome, pathological diagnosis and subsequent complications. RESULTS:
      A total of 75 patients (M:F, 44:31) underwent 115 resectional procedures as part
      of the management of retroperitoneal soft-tissue sarcoma. There were 12 major
      complications for the 115 procedures (morbidity of 8.69%). The 30-day operative
      mortality was zero and the 90-day mortality rate was 1.33% (1/75). Follow-up
      ranged from 16-131 months. The median disease-free survival was 69 months (range,
      59-78 months). Recurrences developed in 46 patients; median time to overall
      recurrence was 13 months (range, 3-71 months). Of these 46, 22 developed
      localised recurrence, which was amenable to further resection. In the cohort of
      patients with recurrent disease, median survival in those who underwent surgery
      was 53 months (range, 30-76 months) and median survival in those who did not
      undergo surgery was 30 months (range, 18-41 months) and this difference was
      statistically significant (log rank, P = 0.01). CONCLUSIONS: Extensive
      resectional surgery with minimal morbidity, devoid of mortality is feasible in
      the treatment of retroperitoneal sarcoma. Development of recurrent disease is a
      significant factor influencing survival; however, localised recurrences are
      amenable to surgery and this can lead to improved survival.

PMID- 20825704
TI  - [The importance of explorations on the pathophysiological mechanisms and
      treatment methods for liver fibrosis].

PMID- 20825705
TI  - [Update on hepatic fibrosis research].

PMID- 20825706
TI  - [The immunological mechanisms of liver fibrosis].

PMID- 20825707
TI  - [Hypoxia and liver fibrosis].

PMID- 20825708
TI  - [Comments on the current diagnostic methods for hepatic fibrosis].

PMID- 20825709
TI  - [The advances of antifibrosis treatment].

PMID- 20825710
TI  - [Stimulation of human hepatic stellate cells by cytochrome P4502E1-mediated
      oxidative stress].
AB  - OBJECTIVE: To explore the stimulation of human hepatic stellate cells by
      Cytochrome P4502E1-mediated oxidative stress. METHODS: HepG2-line was transfected
      with human CYP2E1 plasmid (HepG2/CYP2E1) and empty plasmid (HepG2/PCI)
      respectively. The CYP2E1 expression was evaluated with RT-PCR and Western blot.
      MDA was measured in culture medium of HepG2 cell lines. LX2 was co-incubated with
      HepG2/CYP2E1, HepG2/PCI and HepG2 respectively. The level of hydroxyproline in
      culture medium was examined in 48 hours and the cells were lysated and total RNA
      and protein were extracted. COL-1 and MMP2 mRNA levels were detected by RT-PCR
      and analyzed semi-quantitatively. PICP proteins were measured by ELISA.
      Zymography was performed to investigate MMP2 enzymatic activities. RESULTS: (1)
      MDA from the HepG2 which (HepG2/CYP2E1)express human CYP2E1 (6.51+/-0.25) was
      significantly higher than that from the HepG2 which do not (HepG2/PCI) express
      human CYP2E1 (3.07+/-0.29) and HepG2 alone (2.57+/-0.29). (F=22.66, all P<0.01).
      (2) After co-incubated for 48 hours,the level of hydroxyproline in culture medium
      (35.24+/-3.52) excreted from CYP2E1/LX2 could significantly increase (F=58.89, P
      is less than 0.01). PICP protein (540.01+/-11.38) excreted from CYP2E1/LX2 was
      significantly increased (F=124.97, P<0.01). Zymography showed MMP2 gene
      expression and enzymatic activities of MMP2 had no difference among the groups
      (F=0.29, P>0.05) (F=0.33, P>0.05). CONCLUSIONS: CYP2E1 derived oxidative stress
      mediated stimulation of collagen I synthesis by hepatic stellate cells.
      Hydroxyproline excreted by LX2 was increased by CYP2E1. COL-1mRNA had no
      difference among the groups (F=0.73, P>0.05).

PMID- 20825711
TI  - [Effect of collagens and growth factors (TGFbeta1, PDGF-BB) on cytoskeletal
      reorganization and cell migration in hepatic stellate cells].
AB  - OBJECTIVE: To evaluate the effects of collagens and growth factors TGFbeta1 and
      PDGF-BB on the cytoskeletal components and migration in cultured rat hepatic
      stellate cells (HSCs). METHODS: Primary rat hepatic stellate cells were isolated
      and cultured. A Transwell Chamber system was used to observe the changes of serum
      starved HSCs haptotactic migration (direct stimulation) and chemotactic migration
      (indirect stimulation) after collagens and growth factors treatment. Changes in
      actin cytoskeletal organization were visualized by fluorescence staining using
      FITC-labeled phalloidin and the fluorescence images were recorded using confocal
      microscopy. RESULTS: TGFbeta1 enhanced significantly the motility of primary HSCs
      at 5 ng/ml: for haptotactic migration cells: 131.37+/-3.15 vs 102.93+/-1.01,
      F=40.84, P<0.05; for chemotactic migration cells: 210.17+/-1.78 vs 102.93+/-1.01,
      F=64.53, P<0.05. PDGF-BB enhanced significantly the motility of primary HSCs at
      10 ng/ml (haptotactic migration cells: 203.67+/-7.54 vs 102.93+/-1.01, F=40.90,
      P<0.05; chemotactic migration cells: 319.56+/-11.71 vs 102.93+/-1.01, F=54.57,
      P<0.05); Both chemotactic and haptotactic stimuli with 100 microg/ml collagen
      type I significantly increased HSCs migration: for haptotactic migration cells:
      127.20+/-6.47 VS 102.93+/-1.01, F=41.01, P is less than 0.05; for chemotactic
      migration cells: 201.52+/-11.28 vs 102.93+/-1.01, F=36.49, P<0.05; however,
      collagen type IV had no effect on HSCs migration. Serum-starved, untreated cells
      had a rounded-up morphology. PDGF-BB and TGFbeta1 induced a rapid morphological
      change concomitant with a robust reorganization of actin cytoskeleton in HSCs.
      CONCLUSIONS: Collagen type I, PDGF-BB and TGFbeta1 could induce cell migration in
      HSCs, but collagen type IV has no such effect. PDGF-BB and TGFbeta1 could induce
      the actin cytoskeleton reorganization in HSCs.

PMID- 20825712
TI  - [Individualized respond guidance treatment of chronic hepatitis C with
      combination of peginterferon alpha-2a and ribavirin].
AB  - OBJECTIVE: To study individualized treatment of chronic hepatitis C (CHC)
      genotype 1 patients using respond guided therapy (RGT) of peginterferon alpha-2a
      in combination with ribavirin. METHODS: 140 patients with CHC genotype 1 received
      peginterferon alpha-2a 180 microg injection once a week in combination with
      ribavirin 800-1200 mg/d. Patients achieved RVR after 4 weeks treatment (group A)
      were randomized into 2 subgroups and proceeded with 24 and 48 weeks treatments
      (subgroups A1 and A2) respectively. Patients who had not received RVR but
      achieved cEVR at week 12 (group B) were further divided into 2 subgroups randomly
      and treated for 48 and 72 weeks (subgroups B1 and B2), respectively. Patients
      with PVR at week 24 were treated for 72 weeks (group C1), while patients without
      PVR at week 24 discontinued treatment (group C2). All Patients were followed-up
      for 24 weeks after the end of treatment. RESULTS: For patients treated for 24
      weeks, the ETR rate was 100%, the SVR rate was 65.9%, and the relapse rate was
      34.1%. For those treated for 48 weeks, the ETR, SVR and relapse rate were 95.3% ,
      82.8% and 12.5% respectively. For those treated for 72 weeks, the above rates
      were 82.1%, 67.9% and 14.3% respectively. SVR rates of subgroup A1 and A2 were
      65.9% and 84.4% respectively and the difference was statistically significant
      (P<0.00). The HCV RNA loads were less than 1x10(6) copy/ml in group A and the SVR
      were 72.7% and 100% respectively with 24 and 48 weeks treatment, and the
      difference was insignificant statistically (P>0.05). SVR in subgroup B1 and B2
      were 78.9% and 73.7% respectively and the difference was statistically
      insignificant (P>0.05). The SVR in group C1 was raised to 55. 6%. CONCLUSIONS:
      RVR and cEVR were respond guided prediction factors for CHC treatment. SVR among
      patients with RVR was higher in 48-week treatment than those with 24 weeks
      treatment. For patients with baseline virus load less than 1x10(6) copy/ml and
      achieved RVR, treatment duration can be shortened to 24 weeks. Treatment
      extension to 72 weeks can not result in SVR increase among patients without RVR
      but with cEVR. However, treatment extension to 72 weeks can increase SVR among
      those patients with PVR.

PMID- 20825713
TI  - [Expression of nuclear factor-kappaB and its regulated cytokines in dendritic
      cells in patients with chronic severe hepatitis B and its clinical significance].
AB  - OBJECTIVE: To investigate the correlation of nuclear factor-kappaB (NF-kappaB)
      level and its regulated cytokines in monocyte-derived dendritic cells (MoDC) with
      illness severity and prognosis in patients with chronic severe hepatitis B
      (CSHB). METHODS: Peripheral blood mononuclear cells (PBMC) were isolated by
      Ficoll density gradient separation from 37 patients with CSHB, 20 chronically HBV
      infected patients, and 20 normal controls. Monocytes were acquired using
      immunomagnetic anti-CD14-beads. Next, monocytes were induced into immature DC
      (iDC) in vitro. On day six, polyI:C was added to induce DC maturation. Then
      mature DCs (mDCs) were collected at 48 h after polyI:C treatment to test the
      expression of NF-kappaB p50 by real time PCR. The supernatants were also
      collected respectively. The expression of TNFalpha and IL-6 in the supernatants
      were measured by ELISA. RESULTS: The expression of NF-kappaB p50 in mDCs of
      patients with CSHB was the highest in three groups (F=19.01, P<0.01). The
      secretion of TNFalpha and IL-6 in mDCs from group CSHB was extremely high when
      compared with the other two groups, the secretions of TNFalpha in groups CSHB,
      CHB and NC were(15317.69+/-4124.90) pg/ml, (9670.29+/-3654.68) pg/ml and
      (6547.43+/-1027.20) pg/ml (F=45.77, P<0.01) respectively, and the productions of
      IL-6 in groups CSHB, CHB and NC were (1423.78+/-375.14) pg/ml, (862.68+/-93.68)
      pg/ml and (567.26+/-167.04) pg/ml (F = 67.60, P is less than 0.01), respectively.
      NF-kappaB p50 showed significant correlations with TNFalpha(r=0.52, P<0.01) and
      IL-6 (r=0.65, P<0.01) in mDCs. Furthermore, the secretions of TNFalpha and IL-6
      in mDCs from group CSHB were negatively associated with PTA (r=-0.41, P=0.01; r=
      0.40, P=0.01), but not with ALT, TBil and virus loads (r=-0.03, P=0.85, r=0.01,
      P=0.93, r=0.01, P=0.95; r=-0.09, P=0.58, r=0.16, P=0.34, r=0.09, P=0.59). No
      significant difference found in the expression of TNFalpha and IL-6 between the
      survival subgroup and the death subgroup in group CSHB (t=0.42, P=0.67; t=0.76,
      P=0.45). CONCLUSIONS: The expression levels of NF-kappaB and its regulated
      cytokines in monocyte-derived DCs in patients with chronic severe hepatitis B
      were up-regulated and perhaps associated positively with the illness severity.

PMID- 20825714
TI  - [Study on a putative, proprotein convertase-cleaved product of HBV core protein
      in vitro].
AB  - OBJECTIVE: To investigate the cleavage of HBV core protein in vivo by proprotein
      convertase furin or its family members and observe the intracellular localization
      of the putative cleaved product. METHODS: Recombinant HBV core protein was
      incubated with furin under different conditions in vitro, and the reaction was
      checked with Western blotting. The recombinant vectors expressed the putative
      cleaved fragment and intact core protein (serves as control) were constructed.
      The stable expression cell lines were established by transfecting constructs into
      HepG2 cell line, for which indirect immunofluorescence staining was used by
      monoclonal anti-HBc against the region shared by core protein and its cleaved
      product .The confocal microscopy was carried out to observe the intracellular
      distribution. RESULTS: HBV core protein was cleaved by furin in vitro under
      different tested conditions. The molecular weight of the major cleaved product
      just about 15,000 was in concordance with the expectation. The expressed cleaved
      fragment could react to the monoclonal antibody against core protein, and mainly
      located in cytosol in particle style just like the intact core protein.
      CONCLUSION: HBV core protein can be cleaved by furin in vitro. The major cleaved
      product has similar antigenicity and subcellular distribution to core protein.
      These data suggest that proprotein convertase furin or its family members play
      important roles in HBV replication regulation, and the cleaved product may be
      involved in antiviral immunity of HBV infection. Further investigations are
      imperative.

PMID- 20825715
TI  - [Effect of postoperative adjuvant transarterial chemoembolization on late
      recurrence of hepatocellular carcinoma after radical resection].
AB  - OBJECTIVE: To identify the effect of postoperative adjuvant transarterial
      chemoembolization (TACE) on late recurrence of hepatocellular carcinoma (HCC)
      patients after radical resection. METHODS: From year 2001 to 2007, 2436 HCC
      patients underwent radical resection were retrospectively selected. Patients
      underwent resection only were classified into control group, while those received
      adjuvant TACE within 2 months after operation were classified into intervention
      group. Patients were further stratified into those with tumor<or=5 cm and
      presenting low or high risk factors for recurrence, as well as tumor>5 cm and
      presenting low or high risk factors for recurrence. Patients with single tumor
      and without microscopic tumor thrombus were defined as low risk for recurrence;
      otherwise they were defined as high risk. The effect of adjuvant TACE on late (>2
      years) recurrence was evaluated. RESULTS: Recurrence rates of tumor<or=5 cm and
      presenting low, high risk factors for recurrence, as well as tumor>5 cm and
      presenting low, high risk factors for recurrence at 2-year after resection were
      20.38%, 33.06%, 30.54% and 50.82%, respectively in the control group, compared
      with 25.41%, 39.61%, 40.55% and 51.57%, respectively in the intervention group;
      there were no significant differences between intervention group and control
      group in each stratum. For patients recurred or died within the first 2 years
      after resection, the median survival of tumor>5 cm and presenting high risk
      factors for recurrence was 24 months in the intervention group and 12 months in
      the Control group. Only in this subgroup, the survival curve of the intervention
      group was significantly higher than that compared to the control group. For
      patients who remained recurrence free and survived within the first 2 years after
      resection, there were no significant differences in the recurrence curves between
      the intervention group and control group in each stratum; while cumulative
      survival rates in the subgroup of patients with tumor size is less than or equal
      to 5 cm and presenting low risk factors for recurrence were 93.95%, 91.50% and
      88.42% respectively in the control group, compared with 91.70%, 81.32% and 78.19%
      respectively in the intervention group at 3-, 4- and 5-year after resection
      (P=0.0062); for other subgroups, there were no significant differences in the
      survival curves between the intervention group and the control group in each
      stratum. Cox regression model suggested adjuvant TACE was not an independent risk
      factor for late recurrence; however, it might have negative effect on survival
      [hazard ratio (HR)=1.50, P=0.062] for those patients (especially patients with
      tumor is less than or equal to 5 cm and presenting low risk factors for
      recurrence). CONCLUSIONS: The value of adjuvant TACE was mainly due to its
      therapeutic actions on residual tumor or early recurrence. It had no effect on
      postponing or eliminating late recurrence; moreover, it could be a risk rather
      than a benefit in patients at low risk for recurrence (especially those with
      tumor is less than or equal to 5 cm and presenting low risk factors for
      recurrence).

PMID- 20825716
TI  - [Effectiveness of p38MAPK activity during drug resistance against HepG2].
AB  - OBJECTIVE: To investigate the effectiveness of p38MAPK activity during drug
      resistance against HepG2. METHODS: HepG2/CDDP kinetic anti-cancer drug resistance
      model was constructed using anti-cancer drug inducing method and treated with
      P38MAPK inhibitor SB203580 for 24, 48 and 72 hours respectively. Flow cytometry
      (FCM) was used to detect the cell cycle distribution. The IC50 of cisplatin was
      determined by MTT method in vitro. The expressions of P-P38, P-gp, Bcl-2 and Bax
      were examined by Western blot. RESULTS: The HepG2/CDDP kinetic drug resistance
      model was successfully established. The expression of P-P38 increased with the
      increasing drug resistance against HepG2 cells. The models treated with SB203580
      could gradually elevate the sensitivity of HepG2/CDDP to cisplatin, block the
      detention of cell cycle, up-regulate the expression of Bax and down-regulate the
      expressions of Bcl-2 and P-gp. CONCLUSION: The expression of P-P38 increased with
      the increasing drug resistance against hepatocellular carcinoma cells.
      Suppressing the activation of P38 could reverse the drug resistance phenotype
      against hepatocellular carcinoma cells.

PMID- 20825717
TI  - [Effect of siRNA-mediated inhibition of nuclear transcription factor-kappa B on
      apoptosis of hepatocarcinoma cells].
AB  - OBJECTIVE: To investigate the effect of siRNA-mediated inhibition of NF-kappaB on
      apoptosis of hepatocarcinoma cells. METHODS: Specific small interfering RNA
      Targeting NF-kappaB gene was synthesized and transfected into HepG2 cells by
      liposomes. Nested RT-PCR and quantitative RT-PCR were used to detect the mRNA
      expression of NF-kappaB. Immunohistochemistry, enzyme-linked immunosorbent assay
      and Western blot were performed to examine the protein expression of NF-kappaB.
      Annexin V-FITC was used to test cell apoptosis. RESULTS: The expression of NF
      kappaB in HepG2 cells (1.13+/-0.03) was significantly higher (t=27.02, P<0.05)
      than that in normal hepatocytes (0.29+/-0.07). The down-regulation of NF-kappaB
      expression was depended on the dosage of siRNA and the time after transfection.
      72 h after siRNA transfection, NF-kappaB expression reduced by 93% and 62% at the
      mRNA and protein levels, respectively. The apoptosis of HepG2 cells increased by
      85% with NF-kappaB inhibition. CONCLUSIONS: NF-kappaB is abnormally active in
      HepG2 cells and NF-kappaB inhibition mediated by siRNA promotes HepG2 cells
      apoptosis. It suggested that NF-kappaB could be a potential target for HCC
      prevention gene therapy.

PMID- 20825718
TI  - [Analysis of the clinical features of and responsive factors on the prognosis in
      patients with fulminant hepatic failure].
AB  - OBJECTIVE: To judge the prognosis in the patients with fulminant hepatic failure
      and to provide the evidences of correct therapy. METHODS: The clinical features
      and the indexes which may affect the prognosis of the patients with fulminant
      hepatic failure were analyzed. Indexes including prothrombin time (PT), the
      routine biochemical analysis of liver and kidney functions, the plasma levels of
      glucose and ammonia, cortisol, lipases, amylase, age, gender and complications
      were analyzed using the software Statistical Product and Service Solutions
      (SPSS)15.0. The differences between the died and living patients were compared.
      RESULTS: The mortality of the patients was 65% and the highest was 80% for those
      with HBV and HEV coinfection. The age and gender had no influence on mortality (P
      value was 0.423 and 0.728 respectively). HBV infection was the main factor which
      caused fulminant hepatic failure (52%), The next was hepatitis E virus infection
      (39%). Among the indexes analyzed, the plasma levels of total bilirubin, usea
      nitrogen, creatinine, glucose, cholesterol and prothrombin time had positive
      correlations with the prognosis of the patients (P value was 0.005, 0.001, 0.001,
      0.005, 0.010 and 0.049 respectively). The incidence rate of hepatic coma,
      hepatorenal syndrome, and adrenal insufficiency were higher in the died group
      than that in the living group (P value was 0.005, 0.012 and 0.025 respectively).
      But prothrombin time was the only factor which had correlation with the prognosis
      (P=0.035) analyzed by multivariate logistic regression analysis. The scores of
      MELD were higher in the died group than that in living group (t=18.236, P<0.01)
      and especially in the patients with hepatic coma and hepatorenal syndrome. The
      scores of MELD also had positive correlation with the plasma level of TNFa
      (r=0.585, P<0.01). CONCLUSIONS: The HBV infection was the main cause of fulminant
      hepatic failure and HBV and HEV coinfection had the highest mortality. The plasma
      levels of total bilirubin, cholesterol, glucose , prothrombin time and some
      complications including hepatic coma, hepatorenal syndrome, and adrenal
      insufficiency maybe had positive correlations with the prognosis of fulminant
      hepatic failure. The scores of MELD may predict the prognosis of these patients.

PMID- 20825719
TI  - [The changes of interdigestive migrating motor complex in rats with acute liver
      failure].
AB  - OBJECTIVE: To observe the changes and characteristics of interdigestive migrating
      motor complex (MMC) in rat models of acute liver failure. METHODS: 30 rat models
      with acute liver failure were induced with D-galactosamine and another 30 normal
      rats were used as controls. The indexes of MMC recorded by multi-channel
      physiological recorder were compared. RESULTS: No significant differences found
      between the two groups in antral and duodenal MMC cycles and frequencies of
      duodenal and jejunal MMC III phase. Compared with normal controls, the MMC II
      phase in the acute liver failure rats was significantly prolonged (t=-3.97, 
      3.85, P<0.05), the MMC III duration of antrum and duodenum (u=-4.99, t=4.66,
      P<0.05) was shorter and the MMC III frequency of antrum (u=-4.73, P<0.05) was
      faster. In addition, the MMC cycle and MMC III phase of jejunum were
      significantly prolonged (u=-1.63, t=-4.94, P<0.05) and the MMC III phase duration
      was significantly shorter in the acute liver failure rats (t=5.10, P<0.05).
      CONCLUSION: Significantly prolonged MMC II phase characterized by migrating
      clustered contraction, shortened MMC III phase and extended jejunal MMC cycles
      were probably the major contributors to the gastrointestinal motility disorders
      in the rats with acute liver failure.

PMID- 20825720
TI  - [Clinical evaluation of valsartan on portal hypertension in patients with hepatic
      cirrhosis].

PMID- 20825721
TI  - [Inhibitory effects of LNAzyme on expression of hepatitis C virus 5'-NCR Internal
      Ribosome Entry Site in HepG2.9706 cells].

PMID- 20825722
TI  - [Treatment of hemorrhage from gastric varices with percutaneous transhepatic
      variceal embolization and partial splenic embolization].

PMID- 20825723
TI  - [Effect of ligustrazine hydrocklorde on induced alcoholic fatty liver in vitro].

PMID- 20825724
TI  - [Primary hepatocellular carcinoma with pregnancy and delivery: a case report].

PMID- 20825725
TI  - [Interferon caused dysfunction of thyroid in chronic hepatitis C patient: a case
      report].

PMID- 20825726
TI  - [A brief report from the 7th National Conference on Liver Diseases and EASL Day].

PMID- 20825727
TI  - [Hepatic microdialysis technique and its application in hepatic relevant material
      assay].

PMID- 20825728
TI  - [Quantitative evaluation of fatty liver with 1HMRS].

PMID- 20825729
TI  - [Surgical complications after obesity surgery].

PMID- 20825730
TI  - [Late perforation following laparoscopic gastric bypass].
AB  - We present two cases in which the patients were admitted to a local hospital with
      acute abdominal pain four or five months after having undergone laparoscopic
      gastric bypass. In both cases, operation revealed a perforation of the small
      bowel close to the distal anastomosis. In the first case, a massive constipation
      of the small bowel was most likely a contributing factor. In the second case, the
      cause was a kink of the entero-entero anastomosis leading to obstruction and
      finally perforation of the biliary limp. Late perforations are among the rarely
      reported complications associated with gastric bypass but as our two cases
      illustrate they are important to keep in mind.

PMID- 20825731
TI  - [Pelvic floor muscle training in pregnant and parturient women--a survey of a
      Cochrane review].
AB  - Urinary and anal incontinence are prevalent in pregnant and parturient women.
      Pelvic floor muscle training is frequently employed for prevention and treatment.
      A recent Cochrane review is discussed. Fifteen studies with a total of 6,181
      women were included. Pregnant women without urinary incontinence experienced a
      reduction of the risk of developing urinary incontinence in later pregnancy or
      post partum. Peripartum patients with urinary and anal incontinence experienced a
      reduction of their symptoms following training.

PMID- 20825732
TI  - [Oral versus intravenous antibiotic therapy for pyelonephritis in the paediatric
      patient--a survey of a Cochrane review].
AB  - Acute pyelonephritis is a common bacterial infection in children. The recommended
      treatment in Denmark is intravenous ampiciline and gentamycin for at least three
      days followed by oral antibiotics. The available evidence indicates that oral
      antibiotics may be as effective as initial intravenous treatment of children with
      a first attack of pyelonephritis. However, there are no Danish microbiological
      studies covering broad-spectrum oral antibiotics to children with pyelonephritis.
      This impedes generalisation to Danish practice.

PMID- 20825733
TI  - [Non-attendance and late cancellation in private psychiatric practice].
AB  - INTRODUCTION: We investigated non-attendance and cancellation of appointment on
      the day of the appointment in private psychiatric practice in Denmark. MATERIAL
      AND METHODS: Data from 2005 from a quality assurance database for private
      psychiatric practice (QAD3P) and a pilot investigation during one week comprise
      the data basis for this study. A total of 14 psychiatrists, i.e. approximately
      10% of the private practising psychiatrists, reported to the database in 2005 and
      16 psychiatrists reported to the pilot investigation. Non-attendance at the first
      consultation was not recorded. RESULTS: Patients missed 6,7% of the appointments.
      A total of 22,8% of patients missed a minimum of one appointment. There was no
      difference between the sexes. Non-attendance was more common among younger
      patients than among elderly patients. Especially patients with eating disorders
      and emotionally unstable personality disorder had many missed appointments.
      Psychiatrists in regions with few psychiatrists had more non-attendances among
      their patients than psychiatrist in regions with more psychiatrists. There were
      more non-attendances in treatments that ended by non-attendance than in
      treatments with agreed termination. The pilot study saw 17 non-attendances and 23
      cancelled appointments, and among these the psychiatrists found that the reasons
      for cancelling were reasonable in 17 cases. CONCLUSION: Non-attendance and late
      cancellation of appointments at Danish private psychiatric practice amounted to
      6.7%. This occurs in all groups of patients and to all psychiatrists.

PMID- 20825734
TI  - [Magnetic resonance imaging of the scaphoid bone].
AB  - INTRODUCTION: Can junior doctors in orthopaedic surgery interpret magnetic
      resonance imaging (MRI) scans of the scaphoid bone and thereby avoid that
      patients undergo unnecessary immobilization and repeated controls? MATERIAL AND
      METHODS: Patients suspected of having a fracture of the scaphoid bone and with a
      negative x-ray were included in the study. The MRI was performed within a few
      days, and the patient received the results of the MRI the same day in the
      ambulatory. The junior doctor had received training in MRI diagnosis and was not
      allowed to confer with another doctor. Subsequently, the junior doctor's medical
      opinion was reviewed by a radiologist, and the treatment was adjusted if there
      was a discrepancy concerning the diagnosis. Among the 98 eligible patients, 13
      had their MRIs reviewed by the junior doctor in tandem with a specialist;
      therefore, only 85 patients were included in the study. RESULTS: Junior doctors
      found three out of five scaphoid fractures and misinterpreted six. Specificity
      reached 92.5% and the sensitivity 60%. The junior doctors as well as the
      radiologists found 11 fractures of the distal radius that had not been detected
      prior to the MRI. CONCLUSION: We cannot recommend that junior doctors in
      orthopaedic surgery interpret MRI scans. Since studies have showed that is it
      cost-effective to offer early MRI, we will continue doing so, but will wait for
      the final report from the radiologists before initiating treatment.

PMID- 20825735
TI  - [Unspecific effects of certain siRNA molecules used in the treatment of age
      related macular degeneration].
AB  - In clinical trials on age-related macular degeneration, small interfering RNAs
      (siRNAs) targeting vascular endothelial growth factor or its receptor are used to
      inhibit angiogenesis. However, novel data suggests that certain siRNA molecules
      can act unspecifically, without even entering a cell. The sequence- and target
      independent suppression of the angiogenesis seems to be mediated via
      extracellular binding to the toll-like receptors TLR3.

PMID- 20825736
TI  - [Nonconvulsive status epilepticus in children].
AB  - Nonconvulsive status epilepticus (NCSE) is defined by cognitive or behavioural
      changes for at least 30 minutes supplemented with evidence of seizures on
      electroencephalogram (EEG). NCSE constitutes 25% of all cases of status
      epilepticus (SE) and the highest incidence is seen among children below one year
      of age. The condition frequently occurs in patients with neurological injuries,
      specific epilepsy syndromes, learning disabilities and in the course of
      convulsive SE. Aggressive treatment is recommended for complex partial NCSE and
      in comatose patients and cautious treatment is recommended in absence and simple
      partial NCSE.

PMID- 20825737
TI  - [Non-convulsive status epilepticus in 12-year-old].
AB  - This case report describes nonconvulsive status epilepticus of complex partial
      type in a 12-year-old, otherwise healthy girl. The case illustrates the
      characteristic epileptic twilight state with prolonged bizarre behaviour,
      psychosis, confusion and normal mental state. It may be difficult to identify the
      condition in childhood, as changes in behaviour and cognition are often
      recognized later than in adults. Treatment recommendations and other possible
      diagnoses are discussed.

PMID- 20825738
TI  - [Picture of the month: cerebrospinal fluid rhinorrhea].

PMID- 20825739
TI  - [Increase of the number of violent criminal psychiatric patients].

PMID- 20825740
TI  - [Psychiatric treatment sentences].
AB  - INTRODUCTION: Previous Danish studies of the increasing number of sentences to
      psychiatric treatment (SPT) have compared prevalent populations of persons
      undergoing treatment with incident measures of reported crimes. Examining the
      period 1990-2006, we studied incident sentences, taking the type and severity of
      crime into account. MATERIAL AND METHODS: Using data from Statistics Denmark's
      national crime statistics, we have compared time-trends of SPT with time-trends
      of suspended and custodial sentences stratified by type of crime. RESULTS: We
      found that the rise in SPT is primarily attributable to violent offending, and
      that particularly assaults against public servants have contributed to the
      development. CONCLUSION: Regarding violent offences against private persons, the
      time-trends for SPT are parallel to the time-trends for suspended and custodial
      sentences, which may indicate that the same societal factors, including
      propensity to report, police priorities and court practices, are involved both
      generally and amongst psychiatric patients. Conversely, the rise in violent
      offences against public servants is higher amongst SPTs. This can conceivably be
      connected to both conditions, leading to more confrontations and changes in
      practices, e.g., for reporting violence against staff. However, if a civil person
      is the victim of a violent offence, the probability of the perpetrator being a
      psychiatric patient is small and has remained virtually unchanged since 1990.

PMID- 20825741
TI  - [Preoperative functional magnetic resonance imaging in patients with brain
      tumors].
AB  - INTRODUCTION: Functional Magnetic Resonance Imaging (fMRI) allows important
      functions in the brain cortex to be mapped noninvasively. The purpose with this
      work was to investigate a possible correlation between the distance from the
      tumour margin to fMRI activity and postoperative neurological deficits by means
      of a standardised method for measurement of distance. A second purpose was to
      investigate the influence of preoperative fMRI on the neurosurgical decision
      making process. MATERIAL AND METHODS: Retrospective study of 25 patients. The
      inclusion criteria were surgery or biopsy after fMRI plus a three-month
      postoperative assessment. A total of 14 patients complied with these requirements
      (six men and eight women, the mean age was 39 years). fMRI raw data was collected
      using a three tesla magnetic resonance scanner (Signa HDx R14M5, GE Healthcare).
      The distance from the tumour margin to fMRI activation was measured using GE
      reformat version 4.2 after raw data had been postprocessed using GE BrainwavePA
      version 1.3.08130. The neurosurgeons valuation of fMRI in the preoperative
      decision-making process was obtained using a standard questionnaire. RESULTS:
      There was a trend of association between distance from tumour to eloquent
      functional areas and the patients' postoperative neurological outcome (Fisher's
      exact test: distance < 15 mm, p = 0.43; distance < 10 mm, p = 0.14). fMRI proved
      very useful when deciding whether to operate or not (42%), when deciding the
      surgical approach (50%) and when deciding the extent of the surgical approach
      (83%). CONCLUSION: The standardised method for measurement of distance between
      tumour margin and fMRI activity can contribute to the preoperative risk
      assessment in patients with brain tumours.

PMID- 20825742
TI  - [Neonatal consequences of vacuum-assisted delivery].
AB  - About 5000 babies annually, or 1/12 of all births, are the result of vacuum
      assisted delivery in Denmark. Towards the end of the 1990'ies, the US FDA
      published a national warning concerning increasing complications and mortality
      after vacuum-assisted delivery, and other countries followed. One explanation is
      that training is no longer given the needed focus. Recent introduction of new
      requirements on Danish specialist training and the fact that vacuum-assisted
      delivery is an important procedure in obstetrics provides the basis for this
      article which systematically reviews the neonate consequences for the termed baby
      following vacuum-assisted delivery.

PMID- 20825743
TI  - [Reporting adverse reactions and events in randomised clinical trials].
AB  - "Good clinical practice" (GCP) is an international guideline on how to conduct
      clinical trials on medical products involving human participants. Danish statute
      follows the EU trial directive (2001/20/EF) including the GCP guidelines. This
      article summarises the practical implementation of reporting adverse events and
      adverse reactions to the Danish Medicines Agency and the regional ethics
      committee based on the protocol of the ongoing Copenhagen Insulin and Metformin
      Therapy (CIMT) trial.

PMID- 20825744
TI  - [Kaposi's sarcoma interpreted as haematoma].
AB  - Kaposi's sarcoma is a frequent skin cancer in HIV-positive patients, but is
      relatively uncommon in HIV-negative and non-immune compromised patients. We
      present a case of Kaposi's sarcoma of the face and scalp in a HIV-negative male
      with previous facial basal cell carcinoma.

PMID- 20825745
TI  - [Renal and urethral gas production as a complication to infection of the urinary
      tract].
AB  - Emphysematous pyelonephritis (EPN) is a bacterial infection characterised by gas
      production in the renal parenchyma. We present a case with EPN caused by
      Klebsiella pneumoniae sepsis. The 74-year-old woman was admitted in septic shock.
      An acute computed tomography revealed gas bubbles bilaterally in the renal
      parenchyma, left urethra and bladder. Treatment consisted of three types of
      antibiotics and intravenous fluids. She was discharged two months later without
      need for surgical treatment or haemodialysis despite the seriousness of her
      initial condition.

PMID- 20825749
TI  - Words of wisdom. Re: randomized phase III Trial on gemcitabine versus mytomicin
      in recurrent superficial bladder cancer: evaluation of efficacy and tolerance.

PMID- 20825750
TI  - Words of wisdom. Re: clinical results of long-term follow-up of a large, active
      surveillance cohort with localized prostate cancer.

PMID- 20825751
TI  - Words of wisdom. Re: the perils of commercially driven surgical innovation.

PMID- 20825752
TI  - Words of wisdom. Re: peripheral zone prostate cancers: location and
      intraprostatic patterns of spread at histopathology.

PMID- 20825753
TI  - Words of wisdom. Re: lower testosterone levels predict incident stroke and
      transient ischemic attack in older men.

PMID- 20825754
TI  - Words of wisdom. Re: the role of pathology review of transurethral bladder tumor
      resection specimens in the modern era.

PMID- 20825756
TI  - Every minute counts when the renal hilum is clamped during partial nephrectomy.
AB  - BACKGROUND: The safe duration of warm ischemia during partial nephrectomy remains
      controversial. OBJECTIVE: Our aim was to evaluate the short- and long-term renal
      effects of warm ischemia in patients with a solitary kidney. DESIGN, SETTING, AND
      PARTICIPANTS: Using the Cleveland Clinic and Mayo Clinic databases, we identified
      362 patients with a solitary kidney who underwent open (n=319) or laparoscopic
      (n=43) partial nephrectomy using warm ischemia with hilar clamping. MEASUREMENTS:
      Associations of warm ischemia time with renal function were evaluated using
      logistic or Cox regression models first as a continuous variable and then in 5
      min increments. RESULTS AND LIMITATIONS: Median tumor size was 3.4 cm (range: 0.7
      18.0 cm), and median ischemia time was 21 min (range: 4-55 min). Postoperative
      acute renal failure (ARF) occurred in 70 patients (19%) including 58 (16%) who
      had a glomerular filtration rate (GFR) <15 ml/min per 1.73 m(2) within 30 d of
      surgery. Among the 226 patients with a preoperative GFR >or=30 ml/min per 1.73
      m(2) and followed >or=30 d, 38 (17%) developed new-onset stage IV chronic kidney
      disease during follow-up. As a continuous variable, longer warm ischemia time was
      associated with ARF (odds ratio: 1.05 for each 1-min increase; p<0.001) and a
      GFR<15 (odds ratio: 1.06; p<0.001) in the postoperative period, and it was
      associated with new-onset stage IV chronic kidney disease (hazard ratio: 1.06;
      p<0.001) during follow-up. Similar results were obtained adjusting for
      preoperative GFR, tumor size, and type of partial nephrectomy in a multivariable
      analysis. Evaluating warm ischemia in 5-min increments, a cut point of 25 min
      provided the best distinction between patients with and without all three of the
      previously mentioned end points. Limitations include the retrospective nature of
      the study. CONCLUSIONS: Longer warm ischemia time is associated with short- and
      long-term renal consequences. These results suggest that every minute counts when
      the renal hilum is clamped.

PMID- 20825757
TI  - Is classical transurethral resection of the prostate, the gold standard
      endoscopic treatment for benign prostate hyperplasia, in real danger of being
      replaced?

PMID- 20825758
TI  - Meta-analysis of functional outcomes and complications following transurethral
      procedures for lower urinary tract symptoms resulting from benign prostatic
      enlargement.
AB  - CONTEXT: There is a continuous decline in the number of transurethral resections
      of the prostate (TURP) and an increase use of minimally invasive surgical therapy
      (MIST) for lower urinary tract symptoms resulting from benign prostatic
      enlargement. Current results from randomised controlled trials (RCT) and
      methodologically sound prospective studies suggest that some of the proposed
      procedures have the potential to replace TURP. OBJECTIVE: To determine the
      contemporary status of TURP and of the currently most commonly applied
      transurethral MISTs: (1) bipolar TURP, (2) bipolar transurethral vaporisation of
      the prostate (bipolar TUVP), (3) holmium laser enucleation of the prostate
      (HoLEP), and (4) potassium-titanyl-phosphate (KTP) laser vaporisation of the
      prostate. EVIDENCE ACQUISITION: This meta-analysis was based on a systematic
      Medline search assessing the period 1997-2009. All RCTs comparing TURP and the
      most commonly discussed ablative treatments were included. The end points of our
      analyses were functional outcomes and treatment-related adverse events. EVIDENCE
      SYNTHESIS: Twenty-seven publications involving 23 different RCTs with a total of
      2245 patients provided the highest level of evidence available (level 1b) and
      were fully assessed. Meta-analysis was conducted with SAS v.9.1.3 (SAS Institute,
      Cary, NC, USA). Forest plots were produced using the R software. Pooled odds
      ratios and 95% confidence intervals were calculated between various operative
      techniques versus TURP. Functional results between the specific transurethral
      procedures versus TURP were summarised as differences in means. CONCLUSIONS: This
      meta-analysis demonstrates statistically comparable efficacy and overall
      morbidity for MISTs versus contemporary TURP. Type, category (minor vs major),
      and the number of complications (safety profile) vary specifically for each of
      the different transurethral techniques. We feel that the individual patient's
      clinical profile should be carefully assessed to identify the most appropriate
      transurethral technique.

PMID- 20825759
TI  - Complete periprostatic anatomy preservation during robot-assisted laparoscopic
      radical prostatectomy (RALP): the new pubovesical complex-sparing technique.
AB  - BACKGROUND: Puboprostatic ligament preservation has been proposed as a method to
      accelerate continence recovery after radical prostatectomy (RP). However, these
      ligaments present anatomic continuity with the bladder, and there must be
      interruption at some point to expose the prostatourethral junction. OBJECTIVES:
      To describe the surgical steps of pubovesical complex (PVC)-sparing robot
      assisted laparoscopic RP (RALP) and present the preliminary results of our
      technique. DESIGN, SETTING, AND PARTICIPANTS: Thirty PVC-sparing RALP procedures
      were performed in patients <60 yr with clinically localised prostate cancer
      between 2007 and 2009 by the same surgeon. SURGICAL PROCEDURE: The principles of
      bladder neck preservation, tension and energy-free dissection of the bundles as
      well as seminal vesicle sparing are applied. Ventrally, a plane of dissection is
      developed between the detrusor apron and the prostate. The soft connective tissue
      between Santorini's plexus and the prostate is blandly dissected, leaving the
      plexus intact and in place. MEASUREMENTS: The rates and location of positive
      surgical margins (PSM) as well as functional outcomes are presented. RESULTS AND
      LIMITATIONS: Three of 30 patients (10%) had a PSM (two apical margins and one on
      the left posterolateral side). At catheter removal, 24 of 30 patients (80%) were
      dry (0 pads), and 6 of 30 patients (20%) needed one security pad. After 3 mo, 22
      of 30 patients (73%) presented an International Index of Erectile Function score
      >17 (with or without phosphodiesterase type 5 inhibitors). Thirteen of 22 potent
      patients had an Erection Hardness Score of 3, and 9 of 22 patients had a score of
      4. Small sample size, low mean age of enrolled patients (52 yr), and the absence
      of diseases that could impair the continence and potency recovery are some of the
      limitations of the study. Moreover, it is difficult to quantify the effect of
      each applied continence-sparing technique. CONCLUSIONS: The holistic preservation
      of the PVC during RALP is technically feasible. It leads towards an absolute
      preservation of the periprostatic anatomy that may enhance early functional
      outcomes. Further studies are needed to confirm our results.

PMID- 20825760
TI  - Marketing versus science: a fight between necessary evil and stern good over the
      adoption of new technology in medicine.

PMID- 20825761
TI  - Evidence of pre-procedural statin therapy a meta-analysis of randomized trials.
AB  - OBJECTIVES: The purpose of this study was to summarize the evidence of pre
      procedural statin therapy to reduce periprocedure cardiovascular events.
      BACKGROUND: Invasive procedures can result in adverse cardiovascular events, such
      as myocardial infarction (MI) and death. We hypothesized that statins might
      improve clinical outcomes when used before invasive procedures. METHODS: We
      searched the MEDLINE, Cochrane, and clinicaltrials.gov databases from inception
      to February 2010 for randomized, controlled trials that examined statin therapy
      before invasive procedures. Invasive procedures were defined as percutaneous
      coronary intervention, coronary artery bypass grafting (CABG), and noncardiac
      surgery. We required that studies initiated statins before the procedure and
      reported clinical outcomes. A DerSimonian-Laird model was used to construct
      random-effects summary risk ratios. RESULTS: Eight percent of the screened trials
      (21 of 270) met our selection criteria, which included 4,805 patients. The use of
      pre-procedural statins significantly reduced post-procedural MI (risk ratio [RR]:
      0.57, 95% confidence interval [CI]: 0.46 to 0.70, p < 0.0001). This benefit was
      seen after both percutaneous coronary intervention (p < 0.0001) and noncardiac
      surgical procedures (p = 0.004), but not CABG (p = 0.40). All-cause mortality was
      nonsignificantly reduced by statin therapy (RR: 0.66, 95% CI: 0.37 to 1.17, p =
      0.15). Pre-procedural statins also reduced post-CABG atrial fibrillation (RR:
      0.54, 95% CI: 0.43 to 0.68, p < 0.0001). CONCLUSIONS: Statins administered before
      invasive procedures significantly reduce the hazard of post-procedural MI.
      Additionally, statins reduce the risk of atrial fibrillation after CABG. The
      routine use of statins before invasive procedures should be considered.

PMID- 20825762
TI  - Statins before coronary procedures a new indication for an old friend.

PMID- 20825763
TI  - Patients with detectable cocaethylene are more likely to require intensive care
      unit admission after trauma.
AB  - Cocaethylene (CE) is a toxic metabolite that is formed after simultaneous
      consumption of cocaine and ethanol. This potent stimulant is more toxic than
      cocaine and has a longer half-life. The deleterious hemodynamic and
      cardiovascular effects of CE have been proven in animal models. The aim of this
      study is to assess the impact of CE on clinical outcomes after trauma. We
      prospectively enrolled adult (>=13 years) trauma patients requiring admission.
      Predictor variables were age, sex, mechanism of injury, Injury Severity Score,
      base deficit, and toxicology groups (ethanol alone, cocaine alone, CE, and none).
      The outcomes examined were mortality, intensive care unit (ICU) admission, and
      length of hospital stay (LOS). We used nonparametric tests to compare continuous
      variables and chi2 test to compare categorical data. We constructed a logistic
      regression to identify variables that could predict mortality and ICU admission.
      We enrolled 417 patients (74% male; 70% blunt injury; median age, 40 [range, 13
      95]; overall mortality, 2.2%). Urine toxicology and serum ethanol level screens
      classified patients into the following groups: 13.4% ethanol only, 4.1% cocaine
      only, 8.9% CE, and 46% none. Mortality and LOS were not statistically different
      among the groups. In logistic regression analysis, none of the variables were
      statistically significant in predicting mortality. However, the presence of CE
      significantly increased the likelihood of ICU admission (odds ratio, 5.9; 95%
      confidence interval, 1.6-22). The presence of detectable CE in the urine does not
      increase the mortality or LOS in trauma patients requiring admission but does
      increase the likelihood of ICU admission.

PMID- 20825764
TI  - Nuclear terrorism and the problem of burns.

PMID- 20825765
TI  - Value of computed tomography scans in ED dizziness visits: analysis from a
      nationally representative sample.
AB  - OBJECTIVE: The study aimed to assess measures of the clinical value of computed
      tomography (CT) scans in dizziness presentations at the aggregate level. METHODS:
      Using emergency department (ED) dizziness presentations captured in the National
      Hospital Ambulatory Medical Care Survey, the proportion of dizziness visits with
      a CT scan that received a central nervous system (CNS) diagnosis was measured
      yearly (1995-2004) and assessed for a trend over time. The independent
      association of having a CT scan with ED length of stay was examined using
      multivariable linear regression models. RESULTS: The proportion of dizziness
      visits with a CT scan that received a CNS diagnosis dropped 62% from 1995 to 2004
      (P < .05). By 2004, 94.1% (95% confidence interval, 89.4%-96.7%) of dizziness
      visits with a CT did not receive a CNS diagnosis. Having a CT scan was associated
      with a substantial increase in the length of stay with the effect modified by the
      number of other tests performed (range of increase, 40-77 minutes). CONCLUSION:
      The clinical value of CT scans in dizziness presentations at the aggregate level
      may be very low and appears to have dropped over time. Computed tomography scans
      in the general dizziness population could also be an important contributor to ED
      length of stay. Use of CT scans in dizziness presentations should be a target for
      efforts to optimize the effectiveness and efficiency of care.

PMID- 20825766
TI  - Intravenous opioid dosing and outcomes in emergency patients: a prospective
      cohort analysis.
AB  - OBJECTIVES: Pain management in emergency department (ED) patients is variable and
      often inadequate. This study sought to (1) describe the variability in
      intravenous opioid dosing and (2) compare the outcomes that result from the most
      commonly prescribed opioid doses. METHODS: This prospective cohort study enrolled
      emergency patients who were prescribed intravenous morphine or hydromorphone as
      their initial analgesic. Subjects were interviewed at the time of opioid
      administration and 1 to 2 hours after opioid administration. Outcomes included
      the numeric pain score change (using a 0-10 scale), the proportion achieving a
      50% pain score reduction, and the proportion developing side effects. Logistic
      regression was used to assess the effects of demographic, clinical, and treatment
      variables on outcomes. RESULTS: Six hundred ninety-one patients were analyzed.
      Initial equianalgesic dosages varied by a factor of 27 (from 1 mg morphine to 4
      mg hydromorphone). Opioid dose titration occurred in only 21% of patients.
      Outcomes were similar across the range of opioid dosages before and after
      adjusting for potentially confounding variables. Among patients not taking
      opioids at home who received a total of 4 mg of morphine or less. 48% achieved at
      least a 50% pain score reduction and 60% did not want additional analgesics.
      CONCLUSIONS: We found marked opioid dosing variability and infrequent opioid dose
      titration. A substantial number of ED patients with severe pain responded well to
      relatively low opioid dosages. Improved ability to predict opioid dose
      requirements and strategies that increase the use of opioid dose titration in ED
      patients are needed.

PMID- 20825767
TI  - Prediction of blunt traumatic injury in high-acuity patients: bedside examination
      vs computed tomography.
AB  - OBJECTIVE: The addition of spiral computed tomography (SCT) to bedside assessment
      in patients with major trauma may improve detection of significant injury. We
      hypothesized that in high-acuity trauma patients, emergency physicians' ability
      to detect significant injuries based solely on bedside assessment would lack the
      sensitivity needed to exclude serious injuries when compared with SCT. METHODS:
      This was a prospective single-cohort study of high-acuity trauma patients
      routinely undergoing whole-body SCT at a level 1 trauma center from January to
      September 2006. Before SCT, emergency physicians assigned ratings for likelihood
      of injury to 5 body regions on the basis of bedside assessment. These ratings
      were compared with final SCT interpretations. RESULTS: We enrolled 400 patients
      as a convenience sample; 71 were excluded. When a "very low" rating was
      considered negative and "low," "intermediate," "high," and "very high" were
      considered positive, emergency physicians were able to detect head, cervical
      spine, chest, abdominal/pelvic, and thoracic/lumbar spine injuries with
      sensitivities (95% confidence interval) of 100% (98.6%-100%), 97.4% (94.9%
      98.8%), 96.9% (94.2%-98.4%), 97.9% (95.5%-99.1%), and 97.0% (94.3%-98.5%),
      respectively. For overall diagnostic accuracy, areas under the receiver operating
      characteristics curve (95% confidence interval) were 0.87 (0.82-0.92), 0.71 (0.62
      0.81), 0.81 (0.76-0.86), 0.77(0.71-0.83), 0.74 (0.65-0.84), respectively.
      CONCLUSIONS: Bedside assessment by emergency physicians before SCT was sensitive
      in ruling out serious injuries in high-acuity trauma patients with a "very low"
      rating for injury. However, overall diagnostic accuracy was low, suggesting that
      SCT should be considered in most high-acuity patients to prevent missing
      injuries.

PMID- 20825768
TI  - Snow shovel-related injuries and medical emergencies treated in US EDs, 1990 to
      2006.
AB  - BACKGROUND: Injuries and medical emergencies associated with snow shovel use are
      common in the United States. METHODS: This is a retrospective analysis of data
      from the National Electronic Injury Surveillance System. This study analyzes the
      epidemiologic features of snow shovel-related injuries and medical emergencies
      treated in US emergency departments (EDs) from 1990 to 2006. RESULTS: An
      estimated 195 100 individuals (95% confidence interval, 140 400-249 800) were
      treated in US EDs for snow shovel-related incidents during the 17-year study
      period, averaging 11 500 individuals annually (SD, 5300). The average annual rate
      of snow shovel-related injuries and medical emergencies was 4.15 per 100 000
      population. Approximately two thirds (67.5%) of these incidents occurred among
      males. Children younger than 18 years comprised 15.3% of the cases, whereas older
      adults (55 years and older) accounted for 21.8%. The most common diagnosis was
      soft tissue injury (54.7%). Injuries to the lower back accounted for 34.3% of the
      cases. The most common mechanism of injury/nature of medical emergency was acute
      musculoskeletal exertion (53.9%) followed by slips and falls (20.0%) and being
      struck by a snow shovel (15.0%). Cardiac-related ED visits accounted for 6.7% of
      the cases, including all of the 1647 deaths in the study. Patients required
      hospitalization in 5.8% of the cases. Most snow shovel-related incidents (95.6%)
      occurred in and around the home. CONCLUSIONS: This is the first study to
      comprehensively examine snow shovel-related injuries and medical emergencies in
      the United States using a nationally representative sample. There are an
      estimated 11 500 snow shovel-related injuries and medical emergencies treated
      annually in US EDs.

PMID- 20825769
TI  - Accuracy of radiographic readings in the emergency department.
AB  - OBJECTIVES: A review of radiology discrepancies of emergency department (ED)
      radiograph interpretations was undertaken to examine the types of error made by
      emergency physicians (EPs). METHODS: An ED quality assurance database containing
      all radiology discrepancies between the EP and radiology from June 1996 to May
      2005 was reviewed. The discrepancies were categorized as bone, chest (CXR), and
      abdomen (AXR) radiographs and examined to identify abnormalities missed by EPs.
      RESULTS: During the study period, the ED ordered approximately 151 693
      radiographs. Of the total, 4605 studies were identified by radiology as having a
      total of 5308 abnormalities discordant from the EP interpretation. Three hundred
      fifty-nine of these abnormalities were not confirmed by the radiologist (false
      positive). The remainder of the discordant studies represented abnormalities
      identified by the radiologist and missed by the EP (false negatives). Of these
      false-negative studies, 1954 bone radiographs (2.4% of bone x-rays ordered) had
      missed findings with 2050 abnormalities; the most common missed findings were
      fractures and dislocations. Of the 220 AXRs (3.7% of AXRs ordered) with missed
      findings, 240 abnormalities were missed; the most common of these was bowel
      obstruction. Of the 2431 CXRs (3.8% of CXRs ordered), 2659 abnormalities were
      missed; the most common were air-space disease and pulmonary nodules. The rate of
      discrepancies potentially needing emergent change in management based solely on a
      radiographic discrepancy was 85 of 151 693 x-rays (0.056%). CONCLUSIONS:
      Approximately 3% of radiographs interpreted by EPs are subsequently given a
      discrepant interpretation by the radiology attending. The most commonly missed
      findings included fractures, dislocations, air-space disease, and pulmonary
      nodules. Continuing education should focus on these areas to attempt to further
      reduce this error rate.

PMID- 20825770
TI  - The role of risk factors in delayed diagnosis of pulmonary embolism.
AB  - BACKGROUND: Despite diagnostic advances, delays in the diagnosis of pulmonary
      embolism (PE) are common. OBJECTIVE: In this study, we aimed to investigate the
      relationship between delays in the diagnosis of PE and underlying risk factors
      for PE. METHODS: We retrospectively evaluated the records of 408 patients with
      acute PE. Patients were divided into 2 groups, surgical or medical, based on risk
      factors leading to the embolism. Analysis involved demographic characteristics of
      the patients, dates of symptom onset, first medical evaluation, and confirmatory
      diagnostic tests. Diagnostic delay was described as diagnosis of PE more than 1
      week after symptom onset. RESULTS: The mean time to diagnosis for all patients
      was 6.95 +/- 8.5 days (median, 3 days; range, 0-45 days). Of the total number of
      patients, 29.6% had presented within the first 24 hours and 72.3% within the
      first week. The mean time to diagnosis was 4.4 +/- 7.6 days (median, 2 days;
      range, 0-45 days) in the surgical group and 8.0 +/- 8.6 days (median, 4 days;
      range, 0-45 days) in the medical group (P = .000). The mean time to diagnosis in
      the medical group was approximately 4 times greater than that of the surgical
      group on univariate analysis. Early or delayed diagnosis had no significant
      impact on mortality in either group. CONCLUSION: Delay in the diagnosis of PE is
      an important issue, particularly in medical patients. We suggest that a public
      health and educational initiative is needed to improve efficiency in PE
      diagnosis.

PMID- 20825771
TI  - Single-breath counting: a pilot study of a novel technique for measuring
      pulmonary function in children.
AB  - INTRODUCTION: Although peak expiratory flow rate is the conventional way to
      measure asthma severity in adults, its use is problematic in children because it
      is effort dependent. Forced expiratory volume in 1 second (FEV1) and the ratio of
      FEV1 to forced vital capacity (FEV1/FVC) are more accurate, but generally not
      available in the emergency department (ED). A better test is needed. Single
      breath counting (SBC) is the measurement of how far an individual can count in a
      normal speaking voice after a maximal effort inhalation. The count is in cadence
      to a metronome set at 2 beats per second. Previous work has suggested that SBC
      correlates with standard measures of pulmonary function in adults. However, it
      has never been tested in children. OBJECTIVES: The aims of this study are to
      determine if SBC can be easily performed by children and to assess the
      correlation between SBC and standard measures of pulmonary function in a
      pediatric population. METHODS: This was a prospective observational study of a
      convenience sample of children presenting to the pulmonary clinic for scheduled
      pulmonary function testing (PFT). Peak expiratory flow rate, FEV1, FVC, forced
      expiratory flow 25% to 75%, and FEV1/FVC were measured and recorded. After PFT,
      subjects were asked to perform SBC. Three attempts were allowed, and the average
      was recorded. Correlation was determined by the Pearson coefficient. RESULTS:
      Sixty-seven children (ages 5-18 years, 64% male) were enrolled. All were able to
      understand and complete the testing. Indications for PFT included asthma and/or
      allergies (n = 44), cystic fibrosis (n = 9), and other chronic diseases (n = 14).
      The correlations (r) of SBC to peak expiratory flow rate, FEV1, FVC, forced
      expiratory flow 25% to 75%, and FEV1/FVC were 0.55, 0.66, 0.71, 0.44, and -0.29,
      respectively (P < .05 for all results). CONCLUSION: Single-breath counting is
      easy to perform in children, seems to correlate well with standard measures of
      pulmonary function, and shows promise for measuring asthma severity in children.
      Further work to define the range of reference SBC values (as a function of age
      and/or body size) and an evaluation of the utility of SBC in an ED population of
      acute asthmatics is indicated.

PMID- 20825772
TI  - Inappropriate dispatcher decision for emergency medical service users with acute
      myocardial infarction.
AB  - OBJECTIVES: Current guidelines recommend utilization of prehospital emergency
      medical services (EMSs) by patients with ST-elevation myocardial infarction
      (STEMI). The aims of this study were to estimate the percentage of inappropriate
      initial dispatcher decisions and determine their impact on delays in reperfusion
      therapy for EMS users with STEMI. METHODS: As part of a prospective regional
      registry of patients with STEMI, we analyzed the original data for 245 patients
      who called a university hospital-affiliated EMS call center in France. The
      primary study outcome was time to reperfusion therapy calculated from the
      documented date and time of the first patient call. RESULTS: The initial EMS
      dispatcher's decision was appropriate (ie, dispatching a mobile intensive care
      unit staffed by an emergency or critical care physician) for 171 (70%) patients
      and inappropriate for 74 (30%) patients. Inappropriate decisions included
      referring the patient to a family physician (n = 59), providing medical advice (n
      = 9), and dispatching an ambulance (n = 6). Inappropriate initial decisions
      resulted in increased median time to reperfusion for 140 patients receiving
      fibrinolysis (95 vs 53 minutes; P < .001) and 91 patients undergoing primary
      percutaneous coronary intervention (170 vs 107 minutes; P < .001). In-hospital
      mortality was not different between the 2 study groups (6.8% vs 9.9%; P = .42).
      CONCLUSION: The initial dispatcher's decision is inappropriate for 30% of EMS
      users with STEMI and results in substantial delays in time to reperfusion
      therapy. Accuracy of telephone triage should be improved for patients who
      activate EMSs in response to symptoms suggestive of acute coronary syndrome.

PMID- 20825773
TI  - Prevalence of neuropathic pain in emergency patients: an observational study.
AB  - OBJECTIVE: Neuropathic pain (NP) in acute conditions has been poorly
      investigated. A diagnostic score, the DN4 scale (DN4), has been developed to help
      physicians to detect and treat NP appropriately. DN4 is a 10-item questionnaire.
      If you have 4 or more positive responses out of 10 items, the answer to the
      questionnaire is positive and you have a neuropathic pain. We aimed to determine
      the prevalence of NP in emergency department (ED) patients and to describe this
      population. METHODS: We used the DN4 in the patients with NP visiting the adult
      ED of a university hospital. Patients were asked about the characteristics of
      their pain using a face-to-face questionnaire. RESULTS: Among 533 patients with a
      DN4 score, 114 (21.4%) had NP. Neuropathic pain was independently negatively
      associated with age of 65 years of older (odds ratio [OR], 0.2, 95% confidence
      interval [CI], 0.05-0.8) and positively associated with intense pain (OR, 5.2;
      95% CI, 1.5-18.2), located to the limbs (OR, 2.3; 95% CI, 1.2-4.0). CONCLUSION:
      Neuropathic pain was common in ED patients and associated to a higher level of
      pain.

PMID- 20825774
TI  - Heightened pain perception in illicit substance-using patients in the ED:
      implications for management.
AB  - BACKGROUND: Substance users are commonly perceived to overstate their pain. Few
      data exist comparing pain intensity, perception, and related psychiatric
      comorbidities in the emergency department (ED) population. OBJECTIVE: To compare
      pain severity, duration, interference with function, and psychiatric and mood
      disturbance in substance-using (SU) and non-substance-using (NSU) patients in the
      ED. METHODS: This is a cross-sectional study. The setting is in an urban ED.
      Participants are SU and NSU patients in moderate to severe pain (numerical rating
      scale, 5-10). Outcome measures are as follows: pain intensity and duration, other
      painful conditions, pain-related functional interference (0-10), psychiatric
      disorders, and mood distress (profile of mood scale, 0-44). RESULTS: Of the 148
      patients who enrolled, 28 (19%) reported recent illicit substance use (SU) and
      120 (81%) did not (NSU). The SU patients' mean pain intensity was 8.96
      (confidence interval [CI], 7.47-8.14) vs 7.81 (CI, 8.48-9.45) for NSU (P = .003).
      The SU patients reported higher levels of pain interference. Fifty-four percent
      of SU patients vs 31% of NSU patients reported a psychiatric illness (P = .02).
      Mean Profile of Mood State score was higher in SU (32.3; CI, 27.4-37.1) than in
      NSU (22.5; CI, 20.2-24.8; P < .001). Chronic pain was reported by 29% of SU
      patients vs 16% of NSU patients, and 75% of SU patients vs 58% of NSU patients
      reported another concurrent painful condition (P = .10). CONCLUSIONS: The SU
      patients report more severe pain and functional interference, more psychiatric
      illness and mood distress, and more chronically painful conditions. Given the
      complex interplay between pain, substance use, and mood disorders, increased
      attention should be paid to identifying patients with these associated conditions
      and to facilitating appropriate referrals. Effective treatment of this
      challenging patient population requires treating the entirety of their medical,
      psychiatric, and addictive diseases.

PMID- 20825775
TI  - Nosocomial and community-acquired infection rates of patients treated by
      prehospital advanced life support compared with other admitted patients.
AB  - OBJECTIVES: Nosocomial infections are a large burden to both patients and health
      care organizations, causing hospitals to take measures in an attempt to reduce
      microorganism transmission. Patients treated by emergency medical services are
      one population that has not been studied regarding infection rates. This study
      examines admitted patients treated by advanced life support (ALS) and their
      likelihood of having community-acquired and nosocomial infections. METHODS: A
      retrospective cohort study was conducted of 154 318 admitted patients between
      2003 and 2007. Subjects identified as having either community-acquired or
      nosocomial infections were grouped based on infection type and ALS treatment. The
      proportion of infected patients among total hospital admissions in each of these
      groups was calculated and compared using odds ratios (ORs). RESULTS: A total of
      5418 patients had at least 1 infection while admitted (3653 nosocomial, 1765
      community). The probability of an ALS patient getting a nosocomial infection was
      3.20% versus 2.28% for non-ALS patients (OR, 1.42; 95% confidence interval [CI],
      1.28-1.57). There was no significant difference in community-acquired infections
      between ALS and non-ALS-treated groups (1.22% vs 1.14%; OR, 1.08; 95% CI, 0.92
      1.26). CONCLUSIONS: Despite having similar rates of community-acquired
      infections, patients admitted after ALS treatment had significantly greater risk
      for nosocomial infections. Because causality is not established, it remains
      unknown whether paramedic interventions contributed to the increased rate. Quite
      possibly, these patients are more susceptible to virulent organisms; however,
      prospective research is needed to identify causal relationships. Thus, treatment
      by ALS can be used as an identifier of patients at an increased risk of acquiring
      nosocomial infections.

PMID- 20825776
TI  - ETCO2: a predictive tool for excluding metabolic disturbances in nonintubated
      patients.
AB  - OBJECTIVES: The purpose of this study is to examine the relation between end
      tidal carbon dioxide (ETCO2) measurement and bicarbonate (HCO3) level reflecting
      the patient's metabolic status. METHOD: This prospective cross-sectional study
      has been carried out during a 3-month period in a tertiary care university
      hospital's emergency department (ED). During the study period, every
      spontaneously ventilating ED patient requiring arterial blood gas analysis for
      any medical indication, regardless of presenting symptoms, had a simultaneous
      ETCO2 measurement using a Medlab Cap 10 side stream capnograph. The demographics
      and clinical outcomes of the patients were recorded. RESULTS: Of 399 eligible
      patients, 240 with possible metabolic disturbance were enrolled into the study.
      There was a statistically significant correlation between the value of ETCO2 and
      HCO3 levels (r = 0.506). The mean ET(CO)2 level was statistically significantly
      lower in patients who died (26.5 +/- 7.2, 95% confidence interval [CI], 24.2
      28.6, vs 30 +/- 7.5, 95% CI, 29-31; P = .007) and who had low bicarbonate levels
      (25.7 +/- 6.7, 95% CI, 24.3-27.1, vs 31.6 +/- 7.1, 95% CI, 30.4-32.8; P = .000).
      The value of ET(CO)2 measurement to detect low bicarbonate level was found to be
      significant. The area under the receiver operating characteristic curve was
      0.734, the (+) likelihood ratio for ETCO2 less than or equal to 25 was 2.7, and
      the (-) likelihood ratio for ETCO2 greater than or equal to 36 was 0.05.
      CONCLUSION: ETCO2 values correlate moderately with HCO3 levels and thus might
      predict mortality and metabolic acidosis. Therefore, side stream capnograph can
      be used as a noninvasive diagnostic tool for ruling out suspected severe
      metabolic disturbance in the ED.

PMID- 20825777
TI  - Higher incidence of major complications after splenic embolization for blunt
      splenic injuries in elderly patients.
AB  - BACKGROUND: Nonoperative management (NOM) of blunt splenic injuries has been
      widely accepted, and the application of splenic artery embolization (SAE) has
      become an effective adjunct to NOM. However, complications do occur after SAE. In
      this study, we assess the factors leading to the major complications associated
      with SAE. MATERIALS AND METHODS: Focusing on the major complications after SAE,
      we retrospectively studied patients who received SAE and were admitted to 2 major
      referral trauma centers under the same established algorithm for management of
      blunt splenic injuries. The demographics, angiographic findings, and factors for
      major complications after SAE were examined. Major complications were considered
      to be direct adverse effects arising from SAE that were potentially fatal or were
      capable of causing disability. RESULTS: There were a total of 261 patients with
      blunt splenic injuries in this study. Of the 261 patients, 53 underwent SAE, 11
      (21%) of whom were noted to have 12 major complications: 8 cases of
      postprocedural bleeding, 2 cases of total infarction, 1 case of splenic abscess,
      and 1 case of splenic atrophy. Patients older than 65 years were more susceptible
      to major complications after SAE. CONCLUSION: Splenic artery embolization is
      considered an effective adjunct to NOM in patients with blunt splenic injuries.
      However, risks of major complications do exist, and being elderly is, in part,
      associated with a higher major complication incidence.

PMID- 20825778
TI  - Determinants of markedly increased B-type natriuretic peptide in patients with ST
      segment elevation myocardial infarction.
AB  - BACKGROUND: A modestly increased plasma B-type natriuretic peptide (BNP) level of
      greater than 80 pg/mL has been associated with increased mortality in patients
      with ST-segment elevation myocardial infarction (STEMI). However, the prognostic
      significance of larger increases in BNP during STEMI has not been reported.
      METHODS: A total of 420 patients with STEMI were identified from an
      administrative database, and 91 were found to have a BNP level measured within 24
      hours of hospitalization. All patients underwent detailed angiographic and
      echocardiographic evaluation. Charts were abstracted in a blinded fashion to the
      BNP results. RESULTS: The mean +/- SD age of the participants was 64 +/- 13
      years, and 53 (58%) of the participants were men. The median, 25th percentile,
      and 75th percentile of the BNP value were 366, 142, and 1011 pg/mL, respectively.
      The BNP level increased progressively in 1-, 2-, and 3-vessel coronary disease
      with medians of 253, 351, and 818 pg/mL, respectively (P = .009). Patients with
      grade 3/4 diastolic dysfunction had significantly increased median BNP values vs
      all others, 786 vs 306 pg/mL (P = .03). Eight (9%) patients died during their
      hospitalization. The median BNP values for 83 (91%) survivors and 8 (9%)
      nonsurvivors were 344 and 1420 pg/mL, respectively (P = .007). By multiple
      logistic regression, BNP level more than 500 pg/mL was independently associated
      with female sex, increased number of vessels diseased (>75% stenosis), lower
      ejection fraction, higher creatine kinase level, and lower body mass index.
      CONCLUSION: In patients with STEMI, markedly increased BNP level seems to reflect
      the extent of coronary disease, the degree of associated systolic and diastolic
      dysfunction, and a higher risk of in-hospital mortality.

PMID- 20825779
TI  - Effectiveness of each target body temperature during therapeutic hypothermia
      after cardiac arrest.
AB  - PURPOSE: According to the 2005 American Heart Association Guidelines for
      Cardiopulmonary Resuscitation, unconscious adult patients with a return of
      spontaneous circulation (ROSC) after out-of-hospital cardiac arrest should be
      cooled to 32 degrees C to 34 degrees C for 12 to 24 hours. However, it is unclear
      which target temperature is more adequate. In this study, we prospectively
      evaluated the outcome and adverse effects following 3 target temperatures (32
      degrees C, 33 degrees C, and 34 degrees C) during therapeutic hypothermia with
      ROSC after out-of-hospital cardiac arrest. METHODS: This is a prospective study
      of patients with ROSC (>24 hours) after out-of-hospital cardiac arrest who were
      admitted to the intensive care unit in a tertiary hospital and underwent
      therapeutic hypothermia during a 22-month period between March 2007 and December
      2008. RESULTS: Sixty-two patients were included. The number of male patients was
      44. The mean (SD) ages of the patients was 54.61 (2.002) years. There were 13,
      22, and 28 patients who were enrolled in the target temperatures (32 degrees C,
      33 degrees C, and 34 degrees C, respectively). There were no significant
      differences after each target temperature with respect to mortality and
      neurologic outcomes. Regarding adverse effects, hypotension during the
      maintenance of therapeutic hypothermia significantly increased when the target
      temperature was 32 degrees C (P = .023). Based on multivariate analysis,
      hypotension during the maintenance of therapeutic hypothermia was increased more
      than 6 times at 32 degrees C compared with 33 degrees C (odds ratio, 6.800; 95%
      confidence interval, 1.428-32.373). CONCLUSION: When performing therapeutic
      hypothermia in patients with ROSC after an out-of-hospital cardiac arrest, the
      target temperature would be set to 33 degrees C or 34 degrees C, rather than 32
      degrees C. Further multicenter randomized controlled studies may be needed in the
      future.

PMID- 20825780
TI  - Antivenin remains effective against African Viperidae bites despite a delayed
      treatment.
AB  - BACKGROUND: Viperidae bites represent a public health issue in Africa and are
      responsible for a hemorrhagic syndrome with fatal outcome in the short term. A
      research on Medline database does not reveal any data definitively demonstrating
      the efficiency of antivenom in case of delayed administration. The aim of this
      study, based on a 12-year survey of viperine syndromes in Republic of Djibouti,
      was to compare the normalization of the hemostasis disorders with an early
      administration of antivenin versus a delayed administration. METHODS: A
      retrospective study was conducted from October 1994 to May 2006 in the intensive
      care unit of the French military Hospital, in Djibouti. Seventy-three Viperidae
      envenomed patients were included. Antivenin efficiency in correcting hemostatic
      disorders was analyzed in relation to time to treatment (before or after the 24th
      hour after the bite). RESULTS: Forty-two patients (58%) presented with bleeding.
      A consumptive coagulopathy was found in 68 patients (93%). Antivenin was observed
      to be effective in improving hemostasis, and the time to normalization of
      biologic parameters was similar, whether the treatment was started before or
      after the 24th hour after the bite. CONCLUSION: Antivenin should ideally be
      administered as early as possible. However, in Africa, time to treatment
      generally exceeds 24 hours. The results of the present evidence-based study
      confirm an empirical concept: a delayed time to treatment should in no way
      counterindicate the use of antivenin immunotherapy, in the case of African
      Viperidae bites.

PMID- 20825781
TI  - Outcomes associated with small changes in normal-range cardiac markers.
AB  - INTRODUCTION: Troponin concentrations rising above an institutional cutpoint are
      used to define acute myocardial necrosis, yet it is uncertain what outcomes are
      associated with fluctuations in troponin that do not exceed this level. We
      evaluate the association between troponin fluctuations below an institutional
      upper limit of normal and acute coronary syndrome (ACS). MATERIALS AND METHODS:
      This was a post hoc analysis of the Internet tracking registry of ACS (i*trACS),
      which describes patients presenting to emergency departments (EDs) with suspected
      ACS across the spectrum of risk. Patients were included in this registry if they
      were at least 18 years old and had suspected ACS at the time of their ED visit.
      Inclusions in this analysis required that patients had at least 1 cardiac marker
      (creatine kinase-MB [CK-MB], troponin T, or troponin I) drawn twice within 6
      hours of presentation, with both measures being below the institution's upper
      limit of normal. A marker change was defined as either an increase or decrease
      that exceeded 15% of the institutional upper limit of normal. Acute coronary
      syndrome was defined as a positive stress test, documented myocardial infarction,
      coronary revascularization, or death within 30 days of their ED admission.
      RESULTS: Of 17,713 patient visits, 2162 met inclusion and exclusion criteria.
      There were 1872 patient visits with 2 troponin results and 1312 with 2 CK-MB
      results. Patient visits with increasing troponin had increased odds of ACS
      compared with those with stable troponin levels (odds ratio, 3.6; 95% confidence
      interval, 1.4-9.2). Changing CK-MB and decreasing troponin were not associated
      with increased odds of ACS. CONCLUSIONS: Small increases in troponin
      concentration below the upper limit of normal are associated with increased odds
      of ACS.

PMID- 20825782
TI  - Predictors of respiratory failure among previously healthy children with
      respiratory syncytial virus infection.
AB  - BACKGROUND: Respiratory syncytial virus (RSV)-related disease is the leading
      cause of hospitalization among infants, with approximately 7% to 21% of these
      patients developing acute respiratory failure. OBJECTIVE: The aim of this study
      was to identify clinical variables at initial presentation in the emergency
      department (ED) that may predict the subsequent need for mechanical ventilation
      among previously healthy, RSV-infected children who require pediatric intensive
      care unit (PICU) hospitalization. STUDY DESIGN: This is a retrospective study of
      67 previously healthy, RSV-infected patients admitted from January 1997 to March
      2000 to the PICU. The primary outcome for this study was the need for mechanical
      ventilation. The relationship between clinical variables at initial ED
      presentation and the need for mechanical ventilation were explored using
      univariate and multiple logistic regression analysis. RESULTS: On multivariate
      analysis, the presence of lethargy (odds ratio [OR], 12.2; P = .005), grunting
      (OR, 9.3; P = .01), and a Paco(2) 65 mm Hg or greater (OR, 11.8; P = .013) were
      clinical factors at initial presentation in the ED associated with the subsequent
      need for mechanical ventilation among the study cohort. A developmental model
      that included lethargy, grunting, and a Paco(2) of 65 mm Hg or greater performed
      well as a prediction model. The developmental model had a sensitivity of 71%,
      specificity of 96%, a positive predictive value of 86%, and a negative predictive
      value of 91%. CONCLUSIONS: The presence of lethargy, grunting, and a Paco(2) of
      65 mm Hg or greater at initial presentation in the ED were predictive for the
      subsequent need for mechanical ventilation in previously healthy, RSV-infected
      children admitted to the PICU.

PMID- 20825783
TI  - Epidemiology of balcony fall-related injuries, United States, 1990-2006.
AB  - BACKGROUND: Falls from heights are common in urban areas in the United States.
      This study describes the epidemiology of balcony fall-related injuries requiring
      emergency department (ED) treatment among children and adults in the United
      States from 1990 through 2006. METHODS: In 2009, a retrospective analysis of data
      from the National Electronic Injury Surveillance System of the US Consumer
      Product Safety Commission was conducted to describe the epidemiology of balcony
      fall-related injuries. RESULTS: An estimated 86,500 (95% confidence interval
      [CI], 68,400-104,600) balcony fall-related injuries were treated in US hospital
      EDs from 1990 through 2006; 70% of cases were male; 63% were adults (>=18 years
      old); 94% of injury events occurred at home; 24% of patients were hospitalized;
      and 8 patients died. The rate of balcony fall-related injuries among children
      decreased significantly during 1990 to 2006 and was similar to that of adults by
      the end of the study period. Fall heights ranged from 5 to 87.5 ft. Structural
      failure of the balcony was involved in an estimated 5600 cases. Patients younger
      than 18 years were more likely to sustain a concussion/closed head injury
      (relative risk, 2.42; 95% CI, 1.84-3.18) or skull fracture (relative risk, 5.86;
      95% CI, 2.58-13.30) than adults. CONCLUSIONS: This is the first study of balcony
      fall-related injuries requiring emergency treatment using a nationally
      representative sample. Balcony falls are an important cause of injury in the
      United States. Age, male sex, and warm months of the year were associated with
      balcony fall-related injuries in our study population.

PMID- 20825784
TI  - Revolutionary advances in enhancing patient comfort on patients transported on a
      backboard.
AB  - BACKGROUND: Patients with suspected spinal cord injuries are immobilized to a
      backboard during ambulance and helicopter air transport. It has been well
      documented that patients who are immobilized to a backboard experience discomfort
      and eventually become susceptible to pressure ulcer formation. Because the
      patient lying on a backboard is subjected to high skin interface pressures, it is
      imperative to improve patient comfort and prevent pressure ulcer formation.
      OBJECTIVE: Realizing the dangers of the potentially preventable pressure ulcers,
      our team of scientists, surgeons, and trauma nurses performed a comprehensive
      study of the Back Raft system that was designed to reduce patient discomfort and
      skin interface pressure. METHODS: Pressure under the occipital, scapula, and
      sacral regions of the back was measured using the Tactilus pressure analyzer of
      10 healthy volunteers immobilized on a backboard and a backboard with a Back Raft
      air mattress system. Discomfort levels of each volunteer were measured using a
      Visual Analog Scale. RESULTS: Data from this study indicated that the Back Raft
      significantly reduces discomfort as well as tissue interface pressure in the
      occipital, scapula, and sacral regions of the back. CONCLUSIONS: The
      implementation of an air mattress system analogous to the Back Raft would
      facilitate the prevention of pressure ulcer formation during prehospital care and
      transportation. In 2008, The Centers for Medicare and Medicaid Services enacted a
      policy in which the Centers for Medicare and Medicaid Services can refuse payment
      for hospital-acquired conditions. Pressure ulcers were among the hospital
      acquired conditions within the final rule.

PMID- 20825785
TI  - A time and imaging cost analysis of low-risk ED observation patients: a
      conservative 64-section computed tomography coronary angiography "triple rule
      out" compared to nuclear stress test strategy.
AB  - STUDY OBJECTIVE: The study aimed to examine time and imaging costs of 2 different
      imaging strategies for low-risk emergency department (ED) observation patients
      with acute chest pain or symptoms suggestive of acute coronary syndrome. We
      compared a "triple rule-out" (TRO) 64-section multidetector computed tomography
      protocol with nuclear stress testing. METHODS: This was a prospective
      observational cohort study of consecutive ED patients who were enrolled in our
      chest pain observation protocol during a 16-month period. Our standard
      observation protocol included a minimum of 2 sets of cardiac enzymes at least 6
      hours apart followed by a nuclear stress test. Once a week, observation patients
      were offered a TRO (to evaluate for coronary artery disease, thoracic dissection,
      and pulmonary embolus) multidetector computed tomography with the option of
      further stress testing for those patients found to have evidence of coronary
      artery disease. RESULTS: We analyzed 832 consecutive observation patients
      including 214 patients who underwent the TRO protocol. Mean total length of stay
      was 16.1 hours for TRO patients, 16.3 hours for TRO plus other imaging test, 22.6
      hours for nuclear stress testing, 23.3 hours for nuclear stress testing plus
      other imaging tests, and 23.7 hours for nuclear stress testing plus TRO (P <
      .0001 for TRO and TRO + other test compared to stress test +/- other test). Mean
      imaging times were 3.6, 4.4, 5.9, 7.5, and 6.6 hours, respectively (P < .05 for
      TRO and TRO + other test compared to stress test +/- other test). Mean imaging
      costs were $1307 for TRO patients vs $945 for nuclear stress testing. CONCLUSION:
      Triple rule-out reduced total length of stay and imaging time but incurred higher
      imaging costs. A per-hospital analysis would be needed to determine if patient
      time savings justify the higher imaging costs.

PMID- 20825786
TI  - ED syndromic surveillance for novel H1N1 spring 2009.
AB  - PURPOSE: The aim of this study is to demonstrate the use of emergency department
      (ED) syndromic surveillance in the setting of a novel and unexpected H1N1
      influenza outbreak. BASIC PROCEDURES: Data collection from ED electronic medical
      records was used to track initial chief complaint and discharge International
      Classification of Diseases, Ninth Revision, codes related to influenza-like
      illness (ILI). An alert threshold was generated using cumulative sum sequential
      analysis technique. The data were retrospectively analyzed to identify alerts
      that correlated with novel influenza H1N1 illness. MAIN FINDINGS: Our system
      alerted for ILI earlier than both the official national Centers for Disease
      Control and Prevention (CDC) press release for novel H1N1 and the first
      laboratory confirmed case in our county. PRINCIPAL CONCLUSIONS: Emergency
      department syndromic surveillance can be used to detect unexpected ILI before
      laboratory confirmation and serve as an adjunct to traditional laboratory-guided
      public health alerts. Early identification may allow for more efficient
      laboratory testing and early implementation of respiratory isolation precautions.

PMID- 20825787
TI  - Residential carbon monoxide poisoning from motor vehicles.
AB  - CONTEXT: Although morbidity and mortality from accidental carbon monoxide (CO)
      poisoning are high in the United States, identification of common but poorly
      recognized sources should help prevention efforts. OBJECTIVE: The study aimed to
      describe CO poisoning of home occupants due to a vehicle left running in an
      attached garage. DESIGN: News stories reporting incidents of US CO poisoning were
      collected daily from March 2007 to September 2009 via a news.Google.com search
      and data extracted. PATIENTS: Patients were individuals reported in the media to
      have been poisoned with CO in their home by a vehicle running in the attached
      garage. MAIN OUTCOME MEASURES: Main outcome measures were frequency of
      occurrence, geographic distribution, patient demographics, and mortality.
      RESULTS: Of 837 CO poisoning incidents reported in US news media over 2 and a
      half years, 59 (8%) were the result of a vehicle left running in the garage. The
      elderly were disproportionately affected, with incidents most common in states
      with larger elderly populations and 29% of cases with age specified occurring in
      individuals older than 80 years. Among those older than 80 years, 15 of 17 were
      found dead at the scene. CONCLUSIONS: Residential CO poisoning from a vehicle
      running in the garage is common, disproportionately affects the elderly, has a
      high mortality rate, and should be preventable with a residential CO alarm.

PMID- 20825788
TI  - Acute cyanide poisoning among jewelry and textile industry workers.
AB  - Limited work has focused on occupational exposures that may increase the risk of
      cyanide poisoning by ingestion. A retrospective chart review of all admissions
      for acute cyanide poisoning by ingestion for the years 1988 to 2008 was conducted
      in a tertiary university hospital serving the largest population in the country
      working in jewelry and textile facilities. Of the 9 patients admitted to the
      hospital during the study period, 8 (7 males, 1 female; age 36 +/- 11 years, mean
      +/- SD) attempted suicide by ingestion of potassium cyanide used in their
      profession as goldsmiths or textile industry workers. Five patients had severe
      neurologic impairment and severe metabolic acidosis (pH 7.02 +/- 0.08, mean +/-
      SD) with high anion gap (23 +/- 4 mmol/L, mean +/- SD). Of the 5 severely
      intoxicated patients, 3 received antidote therapy (sodium thiosulfate or
      hydroxocobalamin) and resumed full consciousness in less than 8 hours. All
      patients survived without major sequelae. Cyanide intoxication by ingestion in
      our patients was mainly suicidal and occurred in specific jobs where potassium
      cyanide is used. Metabolic acidosis with high anion is a good surrogated marker
      of severe cyanide poisoning. Sodium thiosulfate and hydroxocobalamin are both
      safe and effective antidotes.

PMID- 20825790
TI  - Point-of-care testing for coagulation studies in a stroke protocol: a time-saving
      innovation.
AB  - STUDY OBJECTIVES: Time counts in thrombolytic therapy for stroke. An
      international normalized ratio (INR) greater than 1.7 may preclude its use. We
      studied whether the use of point-of-care testing (POCT) for INR in the emergency
      department (ED) may substitute for the same test done in the central hospital
      laboratory, thereby reducing time to treatment. METHODS: We performed a
      prospective observational study comparing a POCT analysis of INR (i-STAT-1;
      Abbott Inc, Abbott Park, Ill) with a simultaneously drawn sample sent to the
      central laboratory. We tested a convenience sample of adult patients taking
      warfarin who presented to the ED of a tertiary teaching hospital. RESULTS: Thirty
      two patients were enrolled. A receiver operator curve analysis was performed.
      Sensitivity and specificity were calculated for laboratory INR cutoff of 1.7. The
      area under the curve was 0.979 (95% confidence interval [CI], 0.843-0.991). When
      POCT INR was 2.1, the sensitivity for laboratory INR being higher than 1.7 was
      100% (CI, 62.9%-100.0%), and the specificity was 90.5 (CI, 69.6-98.5). When POCT
      INR was 1.8, the specificity for laboratory INR being lower than 1.7 was 100%
      (CI, 83.7%-100%), and the sensitivity was 62.5% (CI, 24.7%-91.0%). The regression
      coefficient (r) value was 0.9648. CONCLUSION: Correlation of POCT INR with that
      of the central laboratory and receiver operator curve characteristics are
      excellent. In general, POCT INR is about 0.3 higher than the laboratory INR. This
      is not generally of clinical importance, but when using cutoff of 1.7 (central
      laboratory), it may be. We describe a 3-tiered system for use of POCT INR in
      determining use of tissue-type plasminogen activator.

PMID- 20825789
TI  - A simple and useful coma scale for patients with neurologic emergencies: the
      Emergency Coma Scale.
AB  - OBJECTIVES: The Emergency Coma Scale (ECS) was developed in Japan in 2003. We
      planned a multicenter study to evaluate the utility of the ECS by comparison of
      the ECS and the Glasgow Coma Scale (GCS). METHODS: Ten medical facilities,
      including 4 university hospitals in Japan, participated in this study. We
      evaluated and recorded the level of consciousness, using the ECS and GCS, of all
      patients transported to these medical facilities by ambulance. We then performed
      a statistical analysis of the level of rater agreement of each scale using the
      average weighted kappa coefficient according to the types of diagnosis at time of
      discharge and the occupations of the raters. We then evaluated the relationship
      between outcome of patients and their scores on the ECS and GCS by logistic
      regression analysis. RESULTS: The ECS showed the greater agreement among raters
      in patient scoring (0.802). In patients with traumatic brain injury and
      cerebrovascular disease, the ECS also yielded the higher agreement (0.846 and
      0.779, respectively). The ECS score appears to be more strongly related than the
      GCS to patient outcome as measured by the Glasgow Outcome Scale (GOS).
      CONCLUSIONS: Our results showed that the ECS is a simple and readily
      understandable coma scale for a wide range of professionals in the field of
      neurologic emergencies. Furthermore, ECS appears to be suitable for evaluating
      patients in neurologic emergency settings.

PMID- 20825791
TI  - Postdischarge secobarbital after ED migraine treatment decreases pain and
      improves resolution.
AB  - OBJECTIVE: The objective of the study was to determine whether the addition of
      postdischarge oral secobarbital to standard emergency department (ED) migraine
      headache therapy improves pain relief and headache resolution compared with
      placebo. SETTING: The setting is an urban ED with 70 000 yearly visits. METHODS:
      This is an Institutional Review Board-approved, randomized, nonconsecutive,
      double-blinded, concealed, and placebo-controlled clinical trial. Patients with a
      clinical diagnosis of migraine underwent standard ED treatment and were
      discharged with 2 tablets of either secobarbital 100 mg or placebo. At home
      arrival, subjects recorded headache pain on a visual analog scale (VAS), took 1
      tablet, and went to bed, taking the second tablet after 1 hour if not asleep.
      Upon awakening, subjects completed a second VAS and survey. STATISTICAL ANALYSIS:
      The VAS data were analyzed using 2-tailed t test with unequal variance. Headache
      resolution data were analyzed using Fisher exact test. RESULTS: Fifty subjects
      were enrolled. Complete data and follow-up were available for 30 subjects (60%).
      Fourteen subjects received placebo; 16 received secobarbital. Secobarbital
      subjects reported an average headache pain decrease of 25 mm (-13 to -38)
      compared with an average increase of 3 mm (-13 to 19) in the placebo group (P =
      .01). Ninety-four percent of the secobarbital group vs 50% of the placebo group
      had complete or partial headache resolution (P < .02). All subjects in the
      secobarbital group reported some relief. CONCLUSIONS: Addition of postdischarge
      oral secobarbital to a standard ED migraine treatment regimen decreased headache
      pain at 24 hours after discharge and improved the rate of headache resolution
      compared with placebo.

PMID- 20825792
TI  - A randomized, placebo-controlled trial of ondansetron, metoclopramide, and
      promethazine in adults.
AB  - OBJECTIVES: The objective of the study was to assess whether ondansetron has
      superior nausea reduction compared with metoclopramide, promethazine, or saline
      placebo in emergency department (ED) adults. METHODS: This randomized, placebo
      controlled, double-blinded superiority trial was intended to enroll a convenience
      sample of 600 patients. Nausea was evaluated on a 100-mm visual analog scale
      (VAS) at baseline and 30 minutes after treatment. Patients with a minimum
      preenrollment VAS of 40 mm were randomized to intravenous ondansetron 4 mg,
      metoclopramide 10 mg, promethazine 12.5 mg, or saline placebo. A 12-mm VAS
      improvement in nausea severity was deemed clinically important. We measured
      potential drug adverse effects at baseline and 30 minutes. Patients received
      approximately 500 mL of saline hydration during the initial 30 minutes. RESULTS:
      Of 180 subjects who consented, 163 completed the study. The median age was 32
      years (interquartile range, 23-47), and 68% were female. The median 30-minute VAS
      reductions (95% confidence intervals) and saline volume given for ondansetron,
      metoclopramide, promethazine, and saline were -22 (-32 to -15), -30 (-38 to 
      25.5), -29 (-40 to -21), and -16 (-25 to -3), and 500, 500, 500, and 450,
      respectively. The median 30-minute VAS differences (95% confidence intervals)
      between ondansetron and metoclopramide, promethazine, and saline were -8 (-18.5
      to 3), -7 (-21 to -5.5), and 6 (-7 to 20), respectively. We compared the
      antiemetic efficacy across all treatments with the Kruskal-Wallis test (P = .16).
      CONCLUSIONS: Our study shows no evidence that ondansetron is superior to
      metoclopramide and promethazine in reducing nausea in ED adults. Early study
      termination may have limited detection of ondansetron's superior nausea reduction
      over saline.

PMID- 20825793
TI  - A pilot study on potential new plasma markers for diagnosis of acute
      appendicitis.
AB  - BACKGROUND: Diagnosis of acute appendicitis (AA) remains a surgical dilemma, with
      negative appendectomy rates of 5% to 40% and perforation suggestive for late
      operative intervention in 5% to 30%. The aim of this study is to evaluate new
      plasma markers, representing early neutrophil activation, to improve diagnostic
      accuracy in patients suspected for AA. MATERIALS AND METHODS: Fifty-one patients
      who underwent surgery for AA were included (male-female = 28:23), and blood was
      sampled. Plasma concentrations of 2 neutrophil proteins were measured:
      lactoferrin (LF) and calprotectin (CP). Controls consisted of 27 healthy
      volunteers. C-reactive protein (CRP) and white blood cell count (WBC)
      concentrations were measured for routine patient care. RESULTS: Median plasma
      concentrations for LF and CP were significantly higher in 51 patients with proven
      AA (665 and 766 ng/mL, respectively) than in 27 healthy volunteers (198 and 239
      ng/mL, respectively, P < .001). No clinically relevant correlation exists between
      the plasma levels of LF and CP and the conventional laboratory tests for CRP and
      WBC. CONCLUSIONS: Circulating LF and CP levels are significantly elevated in
      patients with appendicitis and are detectable in plasma using relatively simple
      and low-cost enzyme-linked immunosorbent assays. Furthermore, plasma levels of LF
      and CP give additional information to conventional markers WBC and CRP, making
      them potential new markers for AA diagnosis.

PMID- 20825794
TI  - Factors affecting the prognosis of patients with delayed encephalopathy after
      acute carbon monoxide poisoning.
AB  - OBJECTIVE: Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP)
      is a disease with poor prognosis. The present study was conducted to determine
      the factors that affect the prognosis of DEACMP patients. METHODS: In a
      retrospective study, 46 DEACMP patients were chosen by the following criteria:
      (1) a clear history of acute carbon monoxide poisoning, a distinct "lucid
      interval," and neuropsychologic symptoms; (2) first-time admittance to a hospital
      (within 1 week of onset of disease); and (3) completion of standard treatment
      period in our hospital. All patients received hyperbaric oxygen (HBO(2))
      treatments. RESULTS: Fifty percent (23 of 46) of the DEACMP patients showed
      improvements after HBO(2) treatments. Age, lucid interval, danger-activities of
      daily living scores (assessed at worst conditions), and complications were
      related (P < .05) to the prognosis of DEACMP patients, whereas sex, fundamental
      diseases, HBO(2) treatment in acute stage, intoxication time, unconsciousness
      duration, and GM1 ganglioside administration were not (P > .05) related to
      prognosis. CONCLUSION: Hyperbaric oxygen treatment appears useful in treating
      DEACMP patients; and patients with greater age and more complications, but
      shorter lucid interval and less danger-activities of daily living scores, are
      more likely to have poor prognosis.

PMID- 20825795
TI  - Young patients with chest pain: 1-year outcomes.
AB  - OBJECTIVE: Prior studies found that young adult chest pain patients without known
      cardiac disease with either no cardiac risk factors or a normal electrocardiogram
      (ECG) are at low risk (<1%) for acute coronary syndromes (ACS) and 30-day
      cardiovascular events. Longer-term event rates in this subset of patients are
      unknown. We hypothesized that patients younger than 40 years without past cardiac
      history and a normal ECG are at less than 1% risk for 1-year adverse
      cardiovascular events. METHODS: We conducted a prospective cohort study in an
      urban university emergency department evaluating patients younger than 40 years
      who received an ECG for evaluation of potential ACS. Cocaine users, cancer
      patients, and patients with a history of myocardial infarction or
      revascularization were excluded. Structured data collection at presentation
      included demographics, chest pain description, history, laboratory results, and
      ECG data. Hospital course was followed. Follow-up was obtained by telephone,
      record review, and social security death index search. Our main outcome was 1
      year adverse cardiovascular events (death; acute myocardial infarction [AMI]; or
      revascularization-percutaneous coronary intervention [PCI] or coronary artery
      bypass graft). Descriptive statistics and 95% confidence intervals were used.
      RESULTS: Of 3846 chest pain patients, 609 met criteria. Of those, 35.5% were
      admitted. Patients had a mean age of 34.8 years (SD, 3.8 years). They were most
      often female (57.6%) and black (69.5%). There were 7 patients (1.1%; 95% CI, 0.5%
      2.4%) with adverse cardiovascular events over the year. Of the subset of 560
      patients with a normal/nonspecific ECG, there were 2 deaths (0.4%), 3 AMI (0.5%),
      and 2 PCIs (0.4%) by 1 year for a composite adverse cardiovascular event rate of
      6 (1.1%; 95% CI, 0.4%-2.3%). Of the subset of 269 patients with no cardiac risk
      factors and a normal/nonspecific ECG, there were no deaths, 1 AMI, and 1 PCI for
      a composite adverse cardiovascular event rate at 1 year of 0.3% (0.01%-2.1%). The
      addition of an initial cardiac marker to this group resulted in a cohort that was
      event-free at 1 year (95% CI, 0%-1.4%). CONCLUSIONS: Patients younger than 40
      years without a cardiac history who present to the ED with symptoms consistent
      with ACS but have either no risk factors or a normal or nonspecific ECG have a
      very low rate of adverse events during the subsequent year.

PMID- 20825796
TI  - The implementation of a gastroenteritis education program.
AB  - PURPOSE: The objective of this study is to determine if intensive gastroenteritis
      education results in greater caregiver knowledge and a reduction in future
      emergency department (ED) visits. METHODS: This was a concurrent control,
      prospective, single-blind trial. One hundred five children aged 3 to 48 months
      were assigned to receive an ED-based educational intervention and a home nursing
      education visit or neither. In the ED and 1 and 6 months postvisit, caregivers
      completed a 38-item Caregiver Gastroenteritis Knowledge Questionnaire. RESULTS:
      One month postintervention, the scores in the intervention group had risen
      compared with controls (3.3 vs 0.9, P = .11). At 6 months, the difference was
      negligible. At 1-year follow-up, 37% of children in both groups had an ED any
      cause visit; gastroenteritis visits occurred in 27% and 13%. CONCLUSION: An
      intensive ED and home gastroenteritis education program did not result in a long
      term increase in disease-specific caregiver knowledge or a reduction in future ED
      visits.

PMID- 20825797
TI  - The handshake technique: proposal of a closed manual reduction technique for
      Colles' wrist fracture.
AB  - Colles' fracture is a distal radius injury, with dorsal tilt of the distal radial
      fracture fragment. Its typical treatment involves reduction and plaster cast
      immobilization to restore its anatomical position. Sometimes, reduction maneuver
      may be difficult with poor outcomes, requiring repeated reduction maneuvers or
      eventual surgical treatment. The author proposes a simple, easy, and reliable
      manual reduction technique.

PMID- 20825798
TI  - Venous thromboembolic disease in the HIV-infected patient.
AB  - OBJECTIVE: Infection with the HIV has developed into a chronic illness, with
      longer-term complications increasingly being seen. There is increasing evidence
      that infection with HIV may be associated with a hypercoagulable state. This
      study examines the association of HIV infection with the incidence of both
      pulmonary embolism and deep venous thrombosis. METHODS: This study was a weighted
      analysis of data from National Hospital Discharge Survey, a national annual
      probability survey of discharges from short-stay non-Federal hospitals, from 1996
      2004. The risk of pulmonary embolism and/or deep venous thrombosis in an HIV+
      individual was ascertained for each age group by calculation of an odds ratio
      (OR) with a 95% confidence interval (CI). A common OR was computed across strata
      to evaluate the overall association between PE/DVT and HIV while adjusting for
      effects of age. RESULTS: The overall age-adjusted OR indicates a statistically
      significant increase of 43% for PE in HIV+ individuals as opposed to HIV-
      individuals (OR, 1.43; 95% CI, 1.39-1.46). This increase differs by age group,
      with age group 21 to 50 years having the highest odds for PE among HIV+
      individuals (OR, 1.58; 95% CI, 1.54-1.63). CONCLUSIONS: The data supports the
      hypothesis that HIV-infected individuals are more likely to have clinically
      detected thromboembolic disease as opposed to non-HIV-infected individuals. This
      study reveals up to a 43% increase in OR of developing a PE, 10% increase in
      developing a DVT, and 40% increase in developing PE or DVT in an HIV-infected
      individual over the 9-year study period after adjusting for age.

PMID- 20825799
TI  - Academic practice of emergency medicine in the nation's Veteran's Affairs
      Hospitals.

PMID- 20825800
TI  - The relationship between chronic illness, chronic pain, and socioeconomic factors
      in the ED.
AB  - OBJECTIVES: The study aimed to determine the prevalence of chronic illness and
      chronic pain in emergency department (ED) patients across demographic
      backgrounds. METHODS: This was a cross-sectional study at an urban, level I
      trauma center with 98,000 annual visits. This was a prospective sample of adult
      patients presenting to the ED during a randomized distribution of daily 8-hour
      periods between June 4 and August 26, 2007. Prevalence of chronic illness was
      compared to subject demographics using logistic regression, and prevalence of
      chronic pain was compared using ordinal logistic regression. RESULTS: Six
      thousand nine hundred sixty-one patients presented during the data collection
      periods; 3882 were eligible, and 3132 (82%) were enrolled (51.7% male; age, 41.1
      +/- 15.8 years; range, 18-98 years). Chronic illness was reported in 36.3% of
      patients and chronic pain in 34.9% of patients. Chronic illness was associated
      with homelessness (odds ratio [OR], 1.75; 95% confidence interval [CI], 1.17
      2.61), family income less than $25,000 (OR, 2.27; 95% CI, 1.60-3.22), and lack of
      access to primary care facilities (OR, 2.68; 95% CI, 2.25-3.21). Chronic pain was
      associated with homelessness (OR, 2.56; 95% CI, 1.79-3.64), family income less
      than $25,000 (OR, 2.54; 95% CI, 1.91-3.39), and lack of access to primary care
      facilities (OR, 1.47; 95% CI, 1.26-1.70). CONCLUSIONS: Patient housing situation,
      family income, and perceived access to primary care medical facilities were
      associated with higher self-reported rates of chronic illness and chronic pain.

PMID- 20825801
TI  - Primary closure of cutaneous abscesses: a systematic review.
AB  - BACKGROUND: Cutaneous abscesses have traditionally been treated with incision and
      drainage followed by secondary healing. Primary closure after incision and
      drainage is an alternative mode of therapy practiced in some parts of the world.
      The current study reviews the experience with primary closure of abscesses.
      METHODS: A systematic literature review was conducted using search terms abscess
      and primary closure. The databases searched included MEDLINE, PubMED, EMBASE,
      CINHAL, and the Cochrane Library between 1950 and 2009. The reference lists of
      the retrieved studies were also manually searched for additional studies. We
      performed a meta-analysis of all randomized clinical trials in which patients
      were randomized to either primary or secondary closure of incised and drained
      abscesses using Review Manager software. RESULTS: Of 33 articles retrieved, there
      were 7 randomized controlled trials in which 915 patients were randomized to
      primary (n = 455) or secondary (n = 460) closure. Many abscesses were located in
      the anogenital region and drained by surgeons. The time to healing after primary
      closure (7.8 days [95% confidence interval {CI}, 7.3-8.3]) was significantly
      shorter than that after secondary closure (15.0 days [95% CI, 14.3-15.7];
      absolute difference, 7.3 days [95% CI, 6.9-7.6]). The rates of abscess recurrence
      after primary closure (7.6% [95% CI, 4.6-10.6]) were similar to those after
      secondary closure (11.1 days [95% CI, 7.5-14.7]; odds ratio, 0.66 [95% CI, 0.35
      1.15]). CONCLUSIONS: Studies from 4 countries suggest that primary closure of
      incised and drained abscesses results in faster healing and similar low abscess
      recurrence rates than after secondary closure. These studies provide a foundation
      for which clinical trials can be conducted in the United States.

PMID- 20825802
TI  - Risk, reasons for refusal, and impact of counseling on consent among ED patients
      declining HIV screening.
AB  - Screening for HIV in the emergency department (ED) is recommended by the Centers
      for Disease Control and Prevention. The relative importance of efforts to
      increase consent among those who currently decline screening is not well
      understood. We compared the risk characteristics reported by patients who decline
      risk-targeted, opt-in ED screening with those who consent. We secondarily
      recorded reasons for declining testing and reversal of the decision to decline
      testing after prevention counseling. Of 199 eligible patients, 106 consented to
      testing and 93 declined. Of those declining, 60 (64.5%) of 93 completed a risk
      assessment. There were no differences in HIV risk behaviors between groups.
      Declining patients reported recent testing in 73.3% of cases. After prevention
      counseling, 4 (6.7%) of 60 who initially declined asked to be tested. Given
      similarities between those who decline and those who consent to testing, efforts
      to increase consent may be beneficial. However, this should be tempered by the
      finding that many declined because of a recent negative test. Emphasizing risk
      during prevention counseling is not a promising strategy for improving opt-in
      consent rates.

PMID- 20825803
TI  - Impact of computerized physician order entry on ED patient length of stay.
AB  - OBJECTIVES: We evaluated whether implementation of computerized physician order
      entry (CPOE) reduces length of stay (LOS) for discharged emergency department
      (ED) patients. METHODS: Emergency department LOS for discharged and admitted
      patients were analyzed in a university-affiliated ED before and after
      introduction of CPOE. Patient demographics and covariates that may affect LOS
      (mode of arrival, provider staffing, daily census, and admission rate) were
      measured. RESULTS: The study included 71,188 patients; 49,175 (69%) were
      discharged from the ED (28, 687 before and 20,488 after CPOE). Length of stay for
      discharged patients decreased from 198 to 168 minutes (difference of -30; 95%
      confidence interval [CI], -28 to -33), whereas LOS for admitted patients
      increased from 405 to 441 minutes (difference of +36; 95% CI, 26-46). After
      controlling for covariates, CPOE implementation was associated with a 23-minute
      decrease in LOS for discharged patients (beta = -23 [95% CI, -26 to -19]).
      CONCLUSION: Implementation of CPOE was associated with a clinically significant
      (23-minute) decrease in LOS among patients who were discharged from the ED.

PMID- 20825804
TI  - Intraosseous line placement for antidote injection by first responders and
      receivers wearing personal protective equipment.
AB  - STUDY OBJECTIVE: Early antidotal therapy may be lifesaving in hazardous materials
      victims. Intravenous line placement is difficult while wearing personal
      protective equipment (PPE). We assessed the ability of protected, experienced
      first responders and limited-experience first receivers to place intraosseous
      (IO) lines for antidote administration. METHODS: Six first responders donned 4
      (A, B, C, and D) and 12 first receivers donned 2 (C and D) United States
      Environmental Protection Agency PPE levels in random order and then placed IO
      lines in 1 of 4 anatomical sites in 12 anesthetized Spanish goats. Observers
      timed interventions until bolus injection of isotonic sodium chloride solution.
      RESULTS: First responders placed IO lines successfully in 100% of cases. The
      median (interquartile range) times to completion (in seconds) were as follows:
      level A, 43.5 (23.0); B, 45.0 (29.0); C, 40.0 (15.0); D, 30.0 (17.0). First
      receivers placed IO lines successfully in 91% of cases. The median (interquartile
      range) times to completion (in seconds) were as follows: level C, 42.0 (19.5); D,
      37.0 (11.0). There were no significant differences in time to completion among
      PPE levels (overall or pairwise) or between operator groups. Two (4%) of 48 line
      placements resulted in recognized extravasation due to penetration of the
      opposite cortex. Infusions were completed successfully. CONCLUSION: Hazardous
      materials first responders and receivers can effectively place IO lines in a goat
      while wearing PPE. Intraosseous lines may facilitate earlier administration of
      antidotes in hazardous materials victims.

PMID- 20825805
TI  - A prospective, randomized, trial of phenobarbital versus benzodiazepines for
      acute alcohol withdrawal.
AB  - OBJECTIVE: The aim of this study was to compare phenobarbital (PB) versus
      lorazepam (LZ) in the treatment of alcohol withdrawal in the emergency department
      (ED) and at 48 hours. METHODS: Prospectively, randomized, consenting patients
      were assessed using a modified Clinical Institute Withdrawal Assessment (CIWA)
      score and given intravenous PB (mean, 509 mg) or LZ (mean, 4.2 mg). At discharge,
      LZ patients received chlordiazepoxide (Librium), and PB patients received
      placebo. RESULTS: Of 44 patients, 25 received PB, and 19 LZ. Both PB and LZ
      reduced CIWA scores from baseline to discharge (15.0-5.4 and 16.8-4.2, P <
      .0001). There were no differences between PB and LZ in baseline CIWA scores (P =
      .3), discharge scores (P = .4), ED length of stay (267 versus 256 minutes, P =
      .8), admissions (12% versus 16%, P = .8), or 48-hour follow-up CIWA scores (5.8
      versus 7.2, P = .6). CONCLUSION: Phenobarbital and LZ were similarly effective in
      the treatment of mild/moderate alcohol withdrawal in the ED and at 48 hours.

PMID- 20825806
TI  - Lidocaine gel as an anesthetic protocol for nasogastric tube insertion in the ED.
AB  - OBJECTIVE: The aim of the study was to evaluate the efficacy of topical 2%
      lidocaine gel in reducing pain and discomfort associated with nasogastric tube
      insertion (NGTI) and compare lidocaine to ordinary lubricant gel in the ease in
      carrying out the procedure. METHODS: This prospective, randomized, double-blind,
      placebo-controlled, convenience sample trial was conducted in the emergency
      department of our tertiary care university-affiliated hospital. Five milliliters
      of 2% lidocaine gel or placebo lubricant gel were administered nasally to alert
      hemodynamically stable adult patients 5 minutes before undergoing a required
      NGTI. The main outcome measures were overall pain, nasal pain, discomfort (eg,
      choking, gagging, nausea, vomiting), and difficulty in performing the procedure.
      Standard comparative statistical analyses were used. RESULTS: The study cohort
      included 62 patients (65% males). Thirty-one patients were randomized to either
      lidocaine or placebo groups. Patients who received lidocaine reported
      significantly less intense overall pain associated with NGTI compared to those
      who received placebo (37 +/- 28 mm vs 51 +/- 26 mm on 100-mm visual analog scale;
      P < .05). The patients receiving lidocaine also had significantly reduced nasal
      pain (33 +/- 29 mm vs 48 +/- 27 mm; P < .05) and significantly reduced sensation
      of gagging (25 +/- 30 mm vs 39 +/- 24 mm; P < .05). However, conducting the
      procedure was significantly more difficult in the lidocaine group (2.1 +/- 0.9 vs
      1.4 +/- 0.7 on 5-point Likert scale; P < .05). CONCLUSION: Lidocaine gel
      administered nasally 5 minutes before NGTI significantly reduces pain and gagging
      sensations associated with the procedure but is associated with more difficult
      tube insertion compared to the use of lubricant gel.

PMID- 20825807
TI  - Is ED disposition associated with intracerebral hemorrhage mortality?
AB  - BACKGROUND: Early deterioration is common in intracerebral hemorrhage (ICH).
      Treatment at tertiary care centers has been associated with lower ICH mortality.
      Guidelines recommend aggressive care for 24 hours irrespective of the initial
      outlook. We examined the frequency of and factors associated with transfer to
      tertiary centers in ICH patients who initially presented at nontertiary emergency
      departments (EDs). We also compared observed with expected mortality in
      transferred and nontransferred patients using published short-term mortality
      predictors for ICH. METHODS: Adult patients who resided in a 5-county region and
      presented to nontertiary EDs with nontraumatic ICH in 2005 were identified.
      Intracerebral hemorrhage score and ICH Grading Scale (ICH-GS) were determined. Of
      16 local hospitals, 2 were designated tertiary care centers. Logistic regression
      was used to assess factors associated with transfer. RESULTS: Of 205 ICH patients
      who presented to nontertiary EDs, 80 (39.0%) were transferred to a tertiary
      center. In multivariate regression, better baseline function (modified Rankin
      scale 0-2 versus 3-5; odds ratio, 0.42, 95% confidence interval, 0.21-0.85, P =
      .016) and black race (odds ratio, 2.28, 95% confidence interval 1.01-5.12, P =
      .046) were associated with transfer. A trend toward higher 30-day mortality was
      observed in nontransferred patients (32.5% versus 45.6%, P = .06). The ICH-GS
      overestimated mortality for all patients, while the ICH Score adequately
      predicted mortality. CONCLUSIONS: We found no significant difference in mortality
      between transferred and nontransferred patients, but the trend toward higher
      mortality in nontransferred patients suggests that further evaluation of ED
      disposition decisions for ICH patients is warranted. Expected ICH mortality may
      be overestimated by published tools.

PMID- 20825808
TI  - Patient history and physician suspicion accurately exclude pregnancy.
AB  - OBJECTIVES: Reliance upon patient assessment in excluding pregnancy is
      questionable. Physicians are encouraged to obtain pregnancy tests in all women of
      childbearing age. We affirmed the accuracy of women and their physicians in
      predicting pregnancy. METHODS: This was a prospective, observational study
      performed in a suburban academic emergency department on adult women with an
      ordered pregnancy test. A standardized gynecologic history was obtained by
      trained research assistants. Subjects estimated their likelihood of pregnancy as
      impossible, possible, or definite. Emergency department physicians estimated the
      likelihood of pregnancy as high, moderate, or low. All women had either a serum
      or urine beta-human chorionic antigen. The diagnostic characteristics of patient
      and physician predictions of pregnancy were calculated with 95% confidence
      intervals (CIs). RESULTS: We enrolled 377 subjects. Median age was 29
      (interquartile range, 22-37) years. Twelve percent of the women were pregnant.
      Women's estimates of pregnancy were as follows: impossible, 64.7%; possible,
      22.5%; and definite, 12.7%. The pregnancy rates among women with estimates of
      impossible, possible, and definite were 0% (95% CI, 0%-1.5%), 4.7% (95% CI, 1.9%
      11.5%), and 89.6% (95% CI, 77.8%-95.5%) (P < .001). Physicians' suspicions of
      pregnancy were high (13.7%), moderate (11.3%), and low (75.1%). The rate of
      pregnancy among low, moderate, and high physician suspicion groups were 0% (95%
      CI, 0%-1.4%), 9.5% (95% CI, 3.8%-22%), and 84.3% (95% CI, 72%-92%) (P < .001).
      CONCLUSIONS: There were no pregnancies among women who estimated pregnancy as
      impossible or whose physicians thought that the likelihood of pregnancy was low.
      Routine pregnancy testing before radiological imaging and medication
      administration may not be required in adult women of childbearing age.

PMID- 20825809
TI  - Primary spontaneous pneumothorax--the role of the emergency observation unit.
AB  - OBJECTIVE: The objective of this study was to compare an expedited 24-hour
      management pathway against traditional inpatient ward management of patients with
      primary spontaneous pneumothorax (PSP) and recurrent spontaneous pneumothorax
      (RSP). METHOD: This was a retrospective chart review of all patients who
      presented with either PSP or RSP to an urban tertiary university hospital in
      2007. RESULTS: Eighty-two patients were included in the study, of which
      approximately a third (27) were managed in the emergency department observation
      unit (EDOU). Five of the EDOU patients were admitted to the ward. Emergency
      department observation unit treatment failures as defined by recurrences within a
      week were comparable to those managed in the ward. One of 5 PSP patients
      receiving only oxygen therapy managed in the EDOU had their pneumothorax recur
      within a week on discharge, whereas none of the 15 receiving needle aspiration
      recurred within a week. For the RSP patients managed in the EDOU, 1 of 3 managed
      with oxygen therapy alone and discharged recurred within a week, whereas with
      needle aspiration, 1 of 4 recurred within a week. The success rate of aspiration
      in our study was comparable with that of published rates (75% versus 50%-60%).
      CONCLUSIONS: Small to moderate PSPs can be safely and efficiently managed within
      24 hours in an EDOU.

PMID- 20825810
TI  - Prehospital delay and its impact on time to treatment in ST-elevation myocardial
      infarction.
AB  - PURPOSES: We performed this study to assess the impact of pre-hospital time on
      the patient's outcome. PROCEDURES: Starting from the symptoms onset, "total time
      to treatment" was divided into less than or equal to 120 minutes and more than
      120 minutes ("pre-hospital time" of <= or > 30 minutes respectively). Adverse
      patient's outcomes were compared in the two subgroups. FINDINGS: Our patients had
      a mean age of 63 (+/-13) years. On-scene time (17.8 +/- 9.4 minutes), was the
      biggest fraction of "pre-hospital time". Comparing the groups with "Total time to
      treatment" of >120 minutes vs. +/-120 minutes ("pre-hospital time" of >30 vs.
      <=30 minutes), mortalities were 4 vs. 0 and transfers to a tertiary care facility
      were 3 vs.1. CONCLUSIONS: Most of the pre-hospital time in STEMI was spent on the
      scene and we suggest "total time to treatment" as a core measure instead of "door
      to balloon time".

PMID- 20825811
TI  - Case series of 226 gamma-hydroxybutyrate-associated deaths: lethal toxicity and
      trauma.
AB  - gamma-Hydroxybutyrate (GHB) and its prodrugs are drugs of abuse that were also
      sold as "dietary supplements." Users present to emergency departments with
      overdose, impaired driving, withdrawal, and associated trauma. We compiled a
      series of GHB-associated deaths to elucidate lethal risks, GHB concentrations,
      cointoxicants, products, uses, and medical interventions. Death records were
      reviewed for toxicology, autopsy findings, and history. Inclusion cutoffs were as
      follows: 5/10 mg/L of GHB (antemortem blood/urine) and 50/20/7 mg/L of GHB
      (postmortem blood/urine/vitreous). Of 226 deaths included, 213 had
      cardiorespiratory arrest and 13 had fatal accidents. Seventy-eight deaths (35%)
      had no cointoxicants. Sixteen deaths involved "supplements" and 1 involved
      pharmaceutical GHB (Xyrem, Jazz Pharmaceuticals, Palo Alto, CA). Postmortem blood
      GHB was 18 to 4400 mg/L (median, 347 mg/L) in deaths negative for cointoxicants.
      Cardiorespiratory arrest occurred prehospital in 100% of 184 cases with available
      history. Of 72 cases with antemortem adverse effects reported, medical assistance
      was delayed or absent in 66; of these, acute GHB ingestion was known in 51,
      including 40 left to "sleep off" adverse effects. Thirty others were left
      "sleeping" and found dead. gamma-Hydroxybutyrate is lethal even without
      cointoxicants, directly and through fatal accidents. Medical interventions were
      frequently delayed or absent despite known GHB ingestion, and witnessed adverse
      events and cardiorespiratory arrest occurred prehospital. Education is needed
      about the lethality of GHB and the necessity for prompt medical intervention.

PMID- 20825812
TI  - An analysis of ED utilization by adults with intellectual disability.
AB  - OBJECTIVES: We sought to identify factors increasing the odds of ED utilization
      among intellectually disabled (ID) adults and differentiate their discharge
      diagnoses from the general adult ED population. METHODS: This was a
      retrospective, observational open cohort study of all ID adults residing at an
      intermediate care facility and their ED visits to a tertiary center (January 1,
      2007-July 30, 2008). We abstracted from the intermediate care facility database
      subjects' demographic, ID, health and adaptive status variables, and their
      requirement of ED care/hospitalization. We obtained from the hospital database
      the primary International Classification of Diseases 9 ED/hospital discharge
      diagnoses for the study and general adult population. Using multivariate logistic
      regression, we computed odds ratios (OR) for ED utilization/hospitalization in
      the cohort. Using the conditional large-sample binomial test, we differentiated
      the study and general populations' discharge diagnoses. RESULTS: A total of 433
      subjects met the inclusion criteria. Gastrostomy/jejunostomy increased the odds
      of ED utilization (OR, 4.16; confidence interval [CI], 1.64-10.58). Partial help
      to feed (OR, 2.59; CI, 1.14-5.88), gastrostomy/jejunostomy (OR, 3.26; CI, 1.30
      8.18), and increasing number of prescribed medications (OR, 1.08; CI, 1.03-1.14)
      increased the odds of hospitalization. Auditory impairment (OR, 0.45; CI, 0.23
      0.88) decreased the odds of hospitalization. For ED discharge diagnoses, ID
      adults were more likely (P < .05) than the general population to have diagnoses
      among digestive disorders and ill-defined symptoms/signs. For hospital discharge
      diagnoses, ID adults were more likely (P < .05) to have diagnoses among
      infectious/parasitic, nervous system, and respiratory disorders. CONCLUSION:
      Among ID adults, feeding status increased the odds of ED utilization, feeding
      status, and increasing number of prescribed medications of that hospitalization.
      Intellectually disabled adults' discharge diagnoses differed significantly from
      the general adult ED population.

PMID- 20825813
TI  - Risk stratification nomogram for nephropathy after abdominal contrast-enhanced
      computed tomography.
AB  - OBJECTIVES: Abdominal contrast-enhanced computed tomography (A-CECT) is widely
      used in emergency departments despite the risk of contrast-induced nephropathy.
      We attempted to develop a risk stratification nomogram for nephropathy in
      patients receiving emergency A-CECT. METHODS: Seven hundred fifty patients who
      received emergency A-CECT between August 2003 and January 2007, with available
      serum creatinine (SCr) measurements before and after A-CECT were included.
      Nephropathy was defined as either an absolute increase of 0.5 mg/dL or greater
      (44 MUmol/L) or a relative increase of 25% or more in the SCr from baseline. A
      nomogram was developed based on multivariate logistic regression analysis using
      clinical variables available before A-CECT. The model was internally validated
      with a bootstrapping method, and performance was assessed by area under the
      receiver operating characteristics curve (AUC) and calibration curve. RESULTS:
      Nephropathy was observed in 34 of 750 patients. A nomogram was developed using
      age (odds ratio, 1.04 per 1-year increment) and baseline SCr (odds ratio, 2.51
      per 1-mg/dL increment) as risk factors. Diagnostic accuracy of the model was fair
      by bias-corrected calibration plot. The AUC of the model was 0.794 (95%
      confidence interval, 0.734-0.854), and the AUC with bootstrapping samples of 200
      repetitions was 0.794 (95% confidence interval, 0.737-0.851). CONCLUSION: The
      risk of nephropathy after emergency A-CECT can be individually predicted by
      internally validated nomogram using clinical variables available before the
      procedure.

PMID- 20825814
TI  - A provider participatory implementation model for HIV testing in an ED.
AB  - BACKGROUND: The Centers for Disease Control and Prevention recommends routine HIV
      screening for adults. OBJECTIVES: Community-based participatory research
      incorporates subjects in the design and conduct of research. We included nurses
      and physicians in the implementation of HIV rapid test use in the emergency
      department (ED). We explored the process, facilitators, and barriers. METHODS: We
      identified clinical champions and trained staff. Physicians obtained consent and
      ordered HIV testing; nurses performed rapid testing. Testing rates were tracked
      by electronic medical record. We conducted regular meetings between staff and
      researchers. Semistructured qualitative interviews with providers were conducted
      at 3 months. RESULTS: By week 15, we administered 121 tests. After the
      eligibility protocol evolved to incorporate ED nursing concerns regarding
      staffing limitations from a random sampling model to one focused on testing
      during nonpeak hours, the weekly number of tests increased. Eighteen percent of
      providers favored nontargeted HIV screening, 27% favored the current model of
      testing at nonpeak hours, 32% supported diagnostic testing, and 18% favored no
      testing or "other." Barriers include written consent, electronic documentation,
      time constraints, and belief that screening is not a core ED duty. Facilitators
      include ease of test administration, belief that ED patients are at higher risk,
      and flexibility to tailor screening efforts according to patient volume.
      CONCLUSIONS: The ED-based HIV testing is feasible within a Veterans Hospital
      Administration setting. Involvement of nursing in a community-based participatory
      research implementation model may facilitate staff acceptance of nontargeted HIV
      screening and be a mechanism to initiate administration of clinical preventive
      services to ED patients with limited primary care contact.

PMID- 20825815
TI  - Tele-ultrasound and paramedics: real-time remote physician guidance of the
      Focused Assessment With Sonography for Trauma examination.
AB  - OBJECTIVES: The aim of this study was to examine the capability of ultrasound
      naive paramedics to obtain interpretable Focused Assessment With Sonography for
      Trauma (FAST) images under the remote direction of emergency physicians (EPs).
      METHODS: Paramedics without experience using ultrasound participated in a 20
      minute lecture covering orientation to the ultrasound machine and the FAST
      examination. The paramedics subsequently performed FAST examinations on a model
      patient, whereas the EP remained in another room, out of visual contact. The EP
      communicated with the paramedic via radio, viewing video from the ultrasound
      machine on a monitor and directing the probe movements to obtain the views of the
      FAST examination. We examined the success rate, time to complete the
      examinations, and adequacy of images from the paramedics' first FAST examination.
      RESULTS: Fifty-one paramedics performed their first FAST examinations and were
      able to successfully complete 100% of the views of the FAST. The median time from
      probe placement to examination completion was 262 seconds (interquartile range,
      206-343 seconds). The median time to complete right upper quadrant (RUQ) versus
      left upper quadrant (LUQ) views was 39 and 50 seconds, respectively. The time to
      complete the LUQ scan took significantly longer than the RUQ (P < .01).
      Paramedics completed cardiac and pelvic view in a median time of 42 and 25
      seconds, respectively. CONCLUSIONS: The study demonstrated that paramedics with
      no prior ultrasound experience could obtain FAST images under remote guidance
      from experienced EPs in less than 5 minutes. Given rapidly evolving data
      transmission technology, this has applicability in battlefield, remote, and rural
      prehospital settings.

PMID- 20825817
TI  - A point-of-care chemistry test for reduction of turnaround and clinical decision
      time.
AB  - PURPOSE: Our study compared clinical decision time between patients managed with
      a point-of-care chemistry test (POCT) and patients managed with the traditional
      central laboratory test (CLT). BASIC PROCEDURE: This was a randomized controlled
      multicenter trial in the emergency departments (EDs) of 5 academic teaching
      hospitals. We randomly assigned patients to POCT or CLT stratified by the
      Emergency Severity Index. A POCT chemistry analyzer (Piccolo; Abaxis, Inc, Union
      City, Calif), which is able to test liver panel, renal panel, pancreas enzymes,
      lipid panel, electrolytes, and blood gases, was set up in each ED. Primary and
      secondary end point was turnaround time and door-to-clinical-decision time. MAIN
      FINDINGS: The total 2323 patients were randomly assigned to the POCT group (n =
      1167) or to the CLT group (n = 1156). All of the basic characteristics were
      similar in the 2 groups. The turnaround time (median, interquartile range [IQR])
      of the POCT group was shorter than that of the CLT group (14, 12-19 versus 55, 45
      69 minutes; P < .0001). The median (IQR) door-to-clinical-decision time was also
      shorter in the POCT compared with the CLT group (46, 33-61 versus 86, 68-107
      minutes; P < .0001). The proportion of patients who had new decisions within 60
      minutes was 72.8% for the POCT group and 12.5% for the CLT group (P < .0001).
      CONCLUSIONS: A POCT chemistry analyzer in the ED shortens the test turnaround and
      ED clinical decision times compared with CLT.

PMID- 20825816
TI  - Comparison of Broselow tape measurements versus physician estimations of
      pediatric weights.
AB  - OBJECTIVE: We sought to determine the agreement of physician estimates compared
      with Broselow tape measurements in accurately determining children's weights. Our
      secondary objective was to evaluate whether physician adjustment of the Broselow
      tape weight measurement is a better estimate of pediatric weight compared with
      either method alone. METHODS: This cross-sectional study was conducted in the
      emergency department (ED) of a tertiary children's hospital. Children between the
      ages of 0 and 14 years consecutively registered in the pediatric ED were eligible
      for enrollment. Height, weight, body mass index, and Broselow tape measurement
      were obtained for all subjects. Blinded ED physicians provided estimates for
      weight and body habitus for enrolled subjects. Physicians next were given the
      Broselow weight measurement and then submitted a second, amended estimate
      (hybrid). Percentage differences were used to analyze the discrepancy between
      estimates and actual weight. Specifically examined were the proportion of
      estimates that fell within 10% of the patients' actual body weights. RESULTS: A
      total of 372 subjects met the inclusion criteria. Mean age was 45.7 months, mean
      body mass index was 17.4, mean weight was 16.8 kg, and 39 participants (18.1%)
      met the definition for obese. Broselow estimates were within 10% of actual weight
      63% of the time, physician estimates were within 10% of the actual weight 43% of
      the time and hybrid estimates 55% of the time. Based on average mean percent
      error, compared with actual weight, Broselow differed by 10.8% (95% confidence
      interval [CI], 9.7-12), hybrid estimate by 11.3% (95% CI, 10.3-12.2), and
      physician estimate by 16.2% (95% CI, 14.7-17.7). The Broselow tape was
      significantly worse than physician estimate for obese patients: 26.4% (95% CI,
      19.7-33.1) versus 16.0% (95% CI, 12.3-19.8). CONCLUSION: The Broselow tape
      generally has greater agreement with actual weight than physician visual
      estimation, except for obese children. Physician adjustment of the Broselow
      measurement also proved to be comparable to the Broselow tape.

PMID- 20825818
TI  - ED technicians can successfully place ultrasound-guided intravenous catheters in
      patients with poor vascular access.
AB  - OBJECTIVE: The objective of the study was to assess the success rate of emergency
      department (ED) technicians in placing ultrasound (US)-guided peripheral
      intravenous (i.v.) catheters. METHODS: In this prospective, observational trial,
      19 ED technicians were taught to use US guidance to obtain i.v. access. Training
      sessions consisted of didactic instruction and hands-on practice. The ED
      technicians were then prospectively followed. The US guidance for i.v. access was
      limited to patients with difficult access. The primary outcome was successful
      peripheral i.v. placement. RESULTS: A total of 219 attempts were recorded, with a
      success rate of 78.5% (172/219). There was a significant correlation between
      operator experience and success rate. Complications were reported in 4.1% of
      patients and included 5 arterial punctures and 1 case of a transient paresthesia.
      CONCLUSIONS: Emergency department technicians can be taught to successfully place
      US-guided IVs in patients with difficult venous access. Teaching this skill to ED
      technicians increases the pool of providers available in the ED to obtain access
      in this patient population.

PMID- 20825819
TI  - Validation of a 6-hour observation period for cocaine body stuffers.
AB  - Often, patients are brought in to the emergency department after ingesting large
      amounts of cocaine in an attempt to conceal it. This act is known as body
      stuffing. The observation period required to recognize potential toxic adverse
      effects in these patients is not well described in the literature. We sought to
      validate a treatment algorithm for asymptomatic cocaine body stuffers using a 6
      hour observation period by observing the clinical course of cocaine body stuffers
      over a 24-hour period. A retrospective chart review was performed on all patients
      evaluated for witnessed or suspected stuffing over 2 years using a standardized
      protocol. One hundred six patients met final inclusion criteria as adult cocaine
      stuffers. No patients developed life-threatening symptoms, and no patients died
      during observation. In our medical setting, stuffers could be discharged after a
      6-hour observation period if there was either complete resolution or absence of
      clinical symptoms.

PMID- 20825820
TI  - ED handoffs: observed practices and communication errors.
AB  - OBJECTIVE: The study objectives were to identify emergency department (ED)
      handoff practices and describe handoff communication errors among emergency
      physicians. METHODS: Two investigators observed patient handoffs among emergency
      physicians in a major metropolitan teaching hospital for 8 weeks. A data
      collection form was designed to assess handoff characteristics including
      duration, location, interruptions, and topics including examination, laboratory
      examinations, diagnosis, and disposition. Handoff errors were defined as
      clinically significant examination or laboratory findings in physician
      documentation that were reported significantly differently during or omitted from
      verbal handoff. Multivariate negative binomial regression models assessed
      variables associated with these errors. The study was approved by the
      institutional review board. RESULTS: One hundred ten handoff sessions
      encompassing 992 patients were observed. Examination handoff errors and omissions
      were noted in 130 (13.1%) and 447 (45.1%) handoffs, respectively. More
      examination errors were associated with longer handoff time per patient, whereas
      fewer examination omissions were associated with use of written or electronic
      support materials. Laboratory handoff errors and omissions were noted in 37
      (3.7%) and 290 (29.2%) handoffs, respectively. Fewer laboratory errors were
      associated with use of electronic support tools, whereas more laboratory handoff
      omissions were associated with longer ED lengths of stay. CONCLUSIONS: Clinically
      pertinent findings reported in ED physician handoff often differ from findings
      reported in physician documentation. These errors and omissions are associated
      with handoff time per patient, ED length of stay, and use of support materials.
      Future research should focus on ED handoff standardization protocols, handoff
      error reduction techniques, and the impact of handoff on patient outcomes.

PMID- 20825821
TI  - Predictors of pain relief and adverse events in patients receiving opioids in a
      prehospital setting.
AB  - OBJECTIVE: The aim of the study was to analyze factors predicting pain relief and
      adverse events in patients receiving opioids for acute pain in a prehospital
      setting. METHODS: In this prospective, observational clinical study, adult
      patients with a numerical rating scale (NRS) score of 5 of 10 or higher who
      required treatment with intravenous opioids for pain control were included. The
      primary outcome variable was final analgesia defined by an NRS score of 3 of 10
      or lower upon arrival to the emergency department. Univariable and multivariable
      analyses were performed to identify predictive factors of pain relief and adverse
      effects. RESULTS: In total, 277 patients (age, 49 +/- 22 years), 205 (74%) of
      whom were male and 154 (56%) with a traumatic pain were included in the analysis.
      Median (interquartile range) NRS scores at baseline and at discharge were 8 of 10
      (7-10) and 3 of 10 (2-5), respectively. The final model had 3 independent
      variables reaching significance. Physician-staffed ambulance transportation (odds
      ratio [OR], 2.42; 95% confidence interval [CI], 1.07-5.49) was the only
      independent predictor of patients' final pain relief. High initial pain scores
      and acetaminophen use were predictive factors for failure of analgesia (OR, 0.79;
      95% CI, 0.68-0.93 for one unit/10; P < .01; and OR, 0.40; 95% CI, 0.21-0.77; P <
      .01, respectively). In the entire sample, 25 (9.0%) presented one adverse effect,
      all mild to moderate in severity, with no significant predictive factors.
      CONCLUSION: Despite advancement in prehospital pain management, pain relief at
      discharge is still inadequate in some patients. Finally, one important message of
      our study is that patients in pain have to be transported by well-equipped and
      staffed ambulances to reevaluate and alleviate pain.

PMID- 20825822
TI  - Acute carbamazepine poisoning treated with resin hemoperfusion successfully.
AB  - Carbamazepine (CBZ) poisoning has been occurring more frequently. We describe the
      use of synthesized resin-absorbed hemoperfusion in the therapy of a 48-year-old
      man who developed carotic, cardiovascular shock and multiorgan dysfunction due to
      a CBZ overdose (the highest concentration of drug >20 mg/L; therapeutic range, 8
      12 mg/L). The treatment was very successful; and the patient eventually was
      discharged with a full recovery and no complications, although his diagnosis and
      treatment had been delayed for 56 hours. Hemoperfusion has a steady clearance of
      this drug without subsequent rebound or potential hazards. Resin hemoperfusion
      should be first considered for acute CBZ intoxication, especially when drug
      induced gastrointestinal hypomotility prevents elimination via the gut and
      patient is under life-threatening condition.

PMID- 20825823
TI  - Estimating the clinical impact of bringing a multimarker cardiac panel to the
      bedside in the ED.
AB  - OBJECTIVES: We examined the use of point-of-care (POC) testing of cardiac
      biomarkers against standard core laboratory testing to determine the time-savings
      and estimate a cost-benefit ratio at our institution. METHODS: We prospectively
      enrolled 151 patients presenting to the emergency department undergoing
      evaluation for acute coronary syndrome and conducted both central laboratory
      troponin T (TnT) testing at baseline and 6 hours as well as POC assays of
      creatine kinase MB, troponin I (TnI), and myoglobin at baseline and 2 hours.
      Sensitivity/specificity was calculated to measure the ability of the POC
      accelerated pathway to identify enzyme elevations at rates parallel to our core
      laboratory. The time-savings were calculated as the difference between the median
      of the current protocol and the accelerated POC pathway. RESULTS: Troponin T
      tests were elevated in 12 patients, which were all detected by the accelerated
      pathway yielding a relative sensitivity of 100%. Time-saving between the
      accelerated pathway and core laboratory showed a saving of 390 minutes (6.5
      hours). The accelerated POC pathway would have benefited 60% (95% confidence
      interval [CI], 52%-68%) of our patients with an estimated cost of $7.40 (95% CI,
      $6.40-$8.70) per direct patient care hour saved. CONCLUSION: Our data suggest
      that the use of an accelerated cardiac POC pathway could have dramatically
      impacted the care provided to a large percentage of our patients at a minimal
      cost per direct patient care hour saved.

PMID- 20825824
TI  - Intussusception in traditional pediatric, nontraditional pediatric, and adult
      patients.
AB  - STUDY OBJECTIVES: We sought to determine the rate of intussusception in 3 age
      groups (traditional pediatric-age [T], nontraditional pediatric-age [N], and
      adult-age [A]) and to compare group characteristics. METHODS: We conducted a
      retrospective records review for patients discharged with diagnosis of
      intussusception between October 1999 and June 2008. RESULTS: Ninety-five cases of
      intussusception were diagnosed as follows: 61 T (64%), 12 N (13%), and 22 A
      (23%). Bloody stool was more common in T patients (P = .016). Air contrast enema
      (36%) and ultrasound (33%) were the most common diagnostic tests in T, whereas
      computed tomography was most common in N (83%) and A (68%) patients. Bowel
      resection occurred more often in older (T) patients (P = .001). The most frequent
      causative pathologic conditions were adenitis (T), Peutz-Jeghers polyp (N), and
      carcinoma (A) and prior gastric bypass in 10 A patients. CONCLUSIONS: The
      incidence of intussusception is substantially higher in nontraditional age groups
      than previously reported. Symptoms, management strategies, and causative
      pathologic conditions varied with age. All adults with intussusception require
      definitive diagnostic testing to determine the cause, given the concerning list
      of possibilities we observed.

PMID- 20825825
TI  - Outcome of elderly patients injured at winter resorts.
AB  - OBJECTIVE: This study examined hospital outcomes in elderly patients injured at
      winter resorts. METHODS: The study included patients age 12 and over who
      presented to a regional trauma center with an acute injury sustained at a winter
      resort. Injury information was prospectively obtained using a questionnaire.
      Emergency department and hospital data were obtained from trauma registry and
      hospital records. RESULTS: Six hundred ninety-three patients presented during the
      study period (67 were >=65 years). Elderly patients were more likely to have a
      preexisting health condition (31% vs 4%, P < .05), undergo hospital admission
      (76% vs 56%, P < .05), have longer hospital length of stay (P < .05), and have
      lower injury severity (P < .05). Both groups had a similar proportion of
      predefined in-hospital complications and comparable hospital discharge outcomes.
      CONCLUSION: Active elderly patients injured at winter resorts had higher
      inpatient admission rates and longer hospital length of stay when compared with a
      younger cohort, despite lower injury severity scores and comparable discharge
      outcomes.

PMID- 20825826
TI  - Spinal arachnoid cyst as an atypical insidious cause of acute back pain.

PMID- 20825827
TI  - Airbag injury and bilateral globe rupture.

PMID- 20825828
TI  - A 2-year survey of treatment of acute atrial fibrillation in an ED.
AB  - OBJECTIVE: Pharmacologic cardioversion of atrial fibrillation (AF) is a
      reasonable mode of treatment if the arrhythmia is of recent onset. Results
      concerning the response rates of different drugs, respectively, in daily clinical
      practice and data with regard to the parameters associated with successful
      cardioversion are not very prevalent. METHODS: Three-hundred seventy-six patients
      who were admitted to the emergency department with acute AF and a duration of
      shorter than 48 hours were enrolled into the AF registry. RESULTS: The most
      effective drugs were flecainide and ibutilide (95% and 76%). Low response rates
      were observed with amiodarone (36%) and the individual use of digoxin or
      diltiazem (19% and 18%). Factors associated with a successful cardioversion were
      a lower blood pressure on admission (P = .002), a shorter time interval between
      the onset of AF and admission to the ED (P = .003), and adherence to treatment
      guidelines (P < .0001). CONCLUSION: The use of flecainide and ibutilide is
      associated with a much higher rate of cardioversion than other drugs we studied.

PMID- 20825829
TI  - ED procedural sedation of elderly patients: is it safe?
AB  - OBJECTIVE: Emergency physicians routinely perform emergency department procedural
      sedation (EDPS), and its safety is well established. We are unaware of any
      published reports directly evaluating the safety of EDPS in older patients (>=65
      years old). Many EDPS experts consider seniors to be at higher risk. The
      objective was to evaluate the complication rate of EDPS in elderly adults.
      METHODS: This was a prospective, observational study of EDPS patients at least 65
      years old, as compared with patients aged 18 to 49 and 50 to 64 years. Physicians
      were blind to the objectives of this research. The study protocol required an ED
      nurse trained in data collection to be present to record vital signs and assess
      for any prospectively defined complications. We used American Society of
      Anesthesiologists (ASA) physical status classification for systemic disease to
      evaluate and account for the comorbidities of patients. We used the Fisher exact
      test for the difference in proportions across age groups and analysis of variance
      for the differences in dosing across age and ASA categories. RESULTS: During the
      4-year study, we enrolled 50 patients at least 65 years old, 149 patients aged 50
      to 64 years, and 665 patients aged 18 to 49 years. Adverse event rates were 8%,
      5.4%, and 5.2%, respectively (P = .563). The at least 65 years age group
      represented a greater percentage of those with higher ASA scores (P < .001). The
      average total sedative dose in the at least 65 years group was significantly
      lower than the comparisons (P < .001). CONCLUSIONS: This study demonstrated no
      statistically significant difference in complication rate for patients 65 years
      or older. There was a significant decrease in mean sedation dosing with increased
      age and ASA score.

PMID- 20825830
TI  - Dense posterior cerebral artery sign as an acute stroke marker: how to accurately
      diagnose it in the appropriate setting.

PMID- 20825831
TI  - Predictors of early clinical deterioration after acute ischemic stroke.
AB  - The measurements for predicting early deterioration of stroke patients is
      controversial. We studied laboratory measurements and previously identified risk
      factors to identify factors or predictors of early deterioration after stroke. A
      prospective observational study of 196 patients with first-time acute ischemic
      stroke was performed. Demographic data, patient histories, laboratory
      measurements, and initial stroke severity assessments were recorded. Patients
      with early deterioration in National Institutes of Health Stroke Scale scores
      (increase >=3 points within 3 days) were defined as having stroke-in-evolution
      (SIE). Thirty patients were diagnosed with SIE. An initial National Institutes of
      Health Stroke Scale score of 12 or higher, a Glasgow Coma Scale score of 12 or
      lower, d-dimers more than 1000, or blood urea nitrogen/creatinine (BUN/Cr) ratio
      higher than 15 were more frequent in SIE patients. After multivariate analysis,
      only a BUN/Cr higher than 15 was independent predictor of SIE. These patients
      were 3.41-fold more likely to have SIE (P = .008). These findings suggest that
      BUN/Cr may be a novel predictor of SIE, potentially useful in emergency
      departments.

PMID- 20825832
TI  - The role of plain radiographs in patients with acute abdominal pain at the ED.
AB  - OBJECTIVE: The purpose of this study was to evaluate the added value of plain
      radiographs on top of clinical assessment in unselected patients presenting with
      acute abdominal pain at the emergency department (ED). METHODS: In a multicenter
      prospective trial, patients with abdominal pain more than 2 hours and less than 5
      days presented at the ED were evaluated clinically, and a diagnosis was made by
      the treating physician. Subsequently, all patients underwent supine abdominal and
      upright chest radiographs, after which the diagnosis was reassessed by the
      treating physician. A final (reference) diagnosis was assigned by an expert
      panel. The number of changes in the primary diagnosis, as well as the accuracy of
      these changes, was calculated. Changes in the level of confidence were evaluated
      for unchanged diagnoses. RESULTS: Between March 2005 and November 2006, 1021
      patients, 55% female, mean age 47 years (range, 19-94 years), were included. In
      117 of 1021 patients, the diagnosis changed after plain radiographs, and this
      change was correct in 39 patients (22% of changed diagnoses and 4% of total study
      population). Overall, the clinical diagnosis was correct in 502 (49%) patients.
      The diagnosis after evaluation of the radiographs was correct in 514 (50%)
      patients, a nonsignificant difference (P = .14). In 65% of patients with
      unchanged diagnosis before and after plain radiography, the level of confidence
      of that diagnosis did not change either. CONCLUSION: The added value of plain
      radiographs is too limited to advocate their routine use in the diagnostic workup
      of patients with acute abdominal pain, because few diagnoses change and the level
      of confidence were mostly not affected.

PMID- 20825833
TI  - Disposable stainless steel vs plastic laryngoscope blades among paramedics.
AB  - BACKGROUND: Several studies have been published in the literature about
      intubation methods, but little is available on intubation equipment used in this
      setting. This is the first prehospital comparison of disposable plastic vs
      disposable stainless steel laryngoscope blades used by paramedics. STUDY
      OBJECTIVE: The objective of this study was to compare prehospital intubation
      success rates on first attempt and overall number of attempts to obtain
      intubations using disposable plastic laryngoscopes blades vs disposable stainless
      steel laryngoscope blades. METHODS: A retrospective prehospital cohort study was
      conducted during two 3-year periods. Two-way contingency table and chi(2) test
      were conducted to determine if there was a difference between the 2 types of
      blades. A proportional odds model with calculated 95% confidence interval (CI)
      and odd ratios were then calculated. RESULTS: A total of 2472 paramedic
      intubations were recorded over the 6-year period. The stainless steel single-use
      blades had a first attempt success rate of 88.9% vs 78.5% with plastic blades (P
      = .01; odds ratio, 1.94; 95% CI, 1.17-3.41). The stainless steel single-use
      laryngoscope blade had a lower number of attempts to successful intubation than
      the plastic blade (88.8% vs 74.3%, respectively) (P < .01; odds ratio, 1.64; 95%
      CI, 1.34-2.00). CONCLUSIONS: In the prehospital setting, stainless steel
      disposable blades were superior to plastic disposable blades in first attempt and
      overall number of attempts to intubation. Until further research is done, we
      recommend use of stainless steel blades for intubations in the prehospital
      setting by paramedics.

PMID- 20825834
TI  - Bilateral EKOS catheter thrombolysis of acute bilateral pulmonary embolism in a
      hemodynamically unstable patient.

PMID- 20825835
TI  - Subarachnoid hemorrhage--a rare complication after intravenous thrombolysis in an
      ischemic stroke patient.

PMID- 20825836
TI  - Etiology of uncompleted exercise stress testing after ED chest pain evaluation.
AB  - OBJECTIVE: Emergency department (ED) chest pain protocols often include an
      exercise stress test (EST) in an outpatient setting to further risk stratify
      patients initially identified as low risk for acute coronary syndrome. Our goal
      was to characterize the noncompliant patient population and delineate reasons for
      uncompleted EST. METHODS: We conducted retrospective chart review of all ED
      scheduled ESTs over a 6-month period. Demographic and compliance information was
      abstracted using standardized instrument, a 1-month consecutive patient subset
      was identified, and a telephone interview was conducted with noncompliant
      patients to determine why they did not complete their EST. RESULTS: From January
      to July 2007, 57% (378/668) of patients were noncompliant with the ED-scheduled
      EST. In the subset, 78% (78/100) did not complete the EST: 58 patients never
      showed for their scheduled EST and 20 patients showed but could not initiate the
      EST because it was deemed inappropriate by health care workers in the
      cardiovascular laboratory or they began the test and it was nondiagnostic.
      Noncompliant patients were more likely to be male, unmarried, African American,
      and uninsured compared to compliant patients (P < .05). The most commonly stated
      reasons for noncompliance were miscommunication, financial, or inconvenience of
      scheduled time. Employed patients were more likely to state financial reasons for
      noncompliance, whereas unemployed patients were more likely to state personal
      reasons (P < .05). CONCLUSIONS: Our findings suggest lack of patient
      comprehension about purpose and logistics of EST completion. Based upon our data,
      the ED should confirm the appropriateness of the EST for each patient and improve
      patient communication and EST availability.

PMID- 20825837
TI  - Pretest probability estimation in the evaluation of patients with possible deep
      vein thrombosis.
AB  - INTRODUCTION: An estimation of pretest probability is integral to the proper
      interpretation of a negative compression ultrasound in the diagnostic assessment
      of lower-extremity deep vein thrombosis. We sought to determine the rate, method,
      and predictors of pretest probability estimation in such patients. METHODS: This
      cross-sectional study of outpatients was conducted in a suburban community
      hospital in 2006. Estimation of pretest probability was done by enzyme-linked
      immunosorbent assay d-dimer, Wells criteria, and unstructured clinical
      impression. Using logistic regression analysis, we measured predictors of
      documented risk assessment. A cohort analysis was undertaken to compare 3-month
      thromboembolic outcomes between risk groups. RESULTS: Among 524 cases, 289
      (55.2%) underwent pretest probability estimation using the following methods:
      enzyme-linked immunosorbent assay d-dimer (228; 43.5%), clinical impression (106;
      20.2%), and Wells criteria (24; 4.6%), with 69 (13.2%) patients undergoing a
      combination of at least two methods. Patient factors were not predictive of
      pretest probability estimation, but the specialty of the clinician was
      predictive; emergency physicians (P < .0001) and specialty clinicians (P = .001)
      were less likely than primary care clinicians to perform risk assessment.
      Thromboembolic events within 3 months were experienced by 0 of 52 patients in the
      explicitly low-risk group, 4 (1.8%) of 219 in the explicitly moderate- to high
      risk group, and 1 (0.4%) of 226 in the group that did not undergo explicit risk
      assessment. CONCLUSIONS: Negative ultrasounds in the workup of deep vein
      thrombosis are commonly interpreted in isolation apart from pretest probability
      estimations. Risk assessments varied by physician specialties. Opportunities
      exist for improvement in the diagnostic evaluation of these patients.

PMID- 20825838
TI  - ED patients: how nonurgent are they? Systematic review of the emergency medicine
      literature.
AB  - Nonurgent visits to emergency departments (ED) are a controversial issue; they
      have been negatively associated with crowding and costs. We have conducted a
      critical review of the literature regarding methods for categorizing ED visits
      into urgent or nonurgent and analyzed the proportions of nonurgent ED visits. We
      found 51 methods of categorization. Seventeen categorizations conducted
      prospectively in triage areas were based on somatic complaint and/or vital sign
      collection. Categorizations conducted retrospectively (n = 34) were based on the
      diagnosis, the results of tests obtained during the ED visit, and hospital
      admission. The proportions of nonurgent ED visits varied considerably: 4.8% to
      90%, with a median of 32%. Comparisons of methods of categorization in the same
      population showed variability in levels of agreement. Our review has highlighted
      the lack of reliability and reproducibility.

PMID- 20825840
TI  - Needle and guidewire visualization in ultrasound-guided internal jugular vein
      cannulation.
AB  - STUDY OBJECTIVE: Reimbursement for ultrasound-guided central lines requires
      documenting the needle entering the vessel lumen. We hypothesized that physicians
      often successfully perform ultrasound-guided internal jugular (IJ) cannulation
      without visualizing the needle in the lumen and that guidewire visualization
      occurs more frequently. METHODS: This prospective, observational study enrolled
      emergency physicians performing ultrasound-guided IJ cannulations over an 8-month
      period. Physicians reported sonographic visualization of the needle or guidewire
      and recorded DVD images for subsequent review. Outcome measures were the
      proportion of successful procedures in which the operator reported seeing the
      needle or guidewire in the vessel lumen and the proportion of successful,
      recorded procedures, in which a reviewer noted the same findings. Procedures were
      deemed successful when functioning central venous catheters were placed. Fisher
      exact test was used for comparisons. RESULTS: Of 41 attempted catheterizations,
      35 (85.4%) were successful. Eighteen of these were recorded on DVD for review.
      The operator reported visualizing the needle within the vessel lumen in 23
      (65.7%) of 35 successful cannulations (95% confidence interval [CI], 47.7%
      80.3%). In 27 cases, the operator attempted to view the guidewire and reported
      doing so in 24 cases (88.9%; 95% CI, 69.7%-97.1%). On expert review, the needle
      was seen penetrating the vessel lumen in 1 (5.6%) of 18 cases (95% CI, 0.3%
      29.4%). Among recorded procedures in which the operator also attempted wire
      visualization, the reviewer could identify the wire within the vessel lumen in 12
      (75.0%) of 16 cases (95% CI, 47.4%-91.7%). CONCLUSIONS: During successful
      ultrasound-guided IJ cannulation, physicians can visualize the guidewire more
      readily than the needle.

PMID- 20825839
TI  - Urgent neurology consultation from the ED for transient ischemic attack.
AB  - OBJECTIVE: The objective of this study was to evaluate the association between
      urgent neurology consultation and outcomes for patients with transient ischemic
      attack (TIA). METHODS: In a secondary analysis of data from 1707 emergency
      department patients with transient ischemic attack from March 1997 to May 1998,
      we compared presentation, management, and outcomes by neurology consultation
      status using generalized estimating equations to adjust for ABCD(2) score and
      clustering by facility and survival analysis for outcomes. RESULTS: Consultation
      was obtained f28% of patients. Median ABCD(2) scores were comparable, but
      consultation was associated with hospital admission (odds ratio, 1.35 [1.02
      1.78], P = .04) and use of antithrombotics (odds ratio, 1.88 [1.20-2.93], P =
      .005). The cumulative stroke risk was significantly lower within 1 week (5.3%
      versus 7.5%, P = .02) but not at 90 days (9.9% versus 11.0%, P = .21).
      CONCLUSIONS: Consultation was not targeted to high-risk patients but was
      associated with some quality of care measures and improved early outcomes;
      however, improvement in 90-day outcomes was not established.

PMID- 20825841
TI  - Do all patients with shoulder dislocations need prereduction x-rays?
AB  - OBJECTIVE: Some would advocate against routine use of prereduction x-rays for
      shoulder dislocations. Our objective was to examine the percent of dislocations
      that also had fractures as a function of age to determine whether there are some
      decades of life with a sufficiently low risk of fracture to avoid routine
      prereduction x-rays. METHODS: This was a retrospective cohort study in 19 New
      Jersey and New York emergency departments. We used The International
      Classification of Diseases, 9th Revision, Clinical Modification (ICD-9) codes to
      identify patients with shoulder dislocations and, among these, those who also had
      fractures. A priori, we chose to group the patients by decade of life. For
      patients with dislocations in each age group, we calculated the percent that also
      had fractures. RESULTS: Of the total 5,408,837 visits in the database, there were
      7209 patients with dislocations, of which 465 (6.5%) had fractures. We found the
      lowest percent of fractures in the 2nd and 3rd decades of life (0.7% [95%
      confidence interval, 0.3%-1.2%] and 0.8% [0.4%-1.3%]). In the 4th and 5th decades
      of life, the percents were 2.6% (1.7%-3.5%) and 4.6% (3.2-6.0%), respectively,
      and they steadily increased to 19% or greater in the 8th to 10th decades of life.
      Omitting the prereduction x-rays for patients in the 2nd and 3rd decades of life
      would reduce the total number of prereduction x-rays by 40%. CONCLUSION: In the
      second and third decades of life, less than 1% of patients with shoulder
      dislocations also had fractures. Because these patients have a sufficiently low
      risk of fracture, routine prereduction x-rays may not be necessary for them.

PMID- 20825842
TI  - Error in body weight estimation leads to inadequate parenteral anticoagulation.
AB  - Parenteral anticoagulation is a cornerstone in the management of venous and
      arterial thrombosis. Unfractionated heparin has a wide dose/response
      relationship, requiring frequent and troublesome laboratorial follow-up. Because
      of all these factors, low-molecular-weight heparin use has been increasing.
      Inadequate dosage has been pointed out as a potential problem because the use of
      subjectively estimated weight instead of real measured weight is common practice
      in the emergency department (ED). To evaluate the impact of inadequate weight
      estimation on enoxaparin dosage, we investigated the adequacy of anticoagulation
      of patients in a tertiary ED where subjective weight estimation is common
      practice. We obtained the estimated, informed, and measured weight of 28 patients
      in need of parenteral anticoagulation. Basal and steady-state (after the second
      subcutaneous shot of enoxaparin) anti-Xa activity was obtained as a measure of
      adequate anticoagulation. The patients were divided into 2 groups according the
      anticoagulation adequacy. From the 28 patients enrolled, 75% (group 1, n = 21)
      received at least 0.9 mg/kg per dose BID and 25% (group 2, n = 7) received less
      than 0.9 mg/kg per dose BID of enoxaparin. Only 4 (14.3%) of all patients had
      anti-Xa activity less than the inferior limit of the therapeutic range (<0.5
      UI/mL), all of them from group 2. In conclusion, when weight estimation was used
      to determine the enoxaparin dosage, 25% of the patients were inadequately
      anticoagulated (anti-Xa activity <0.5 UI/mL) during the initial crucial phase of
      treatment.

PMID- 20825843
TI  - Fatal aortoesophageal fistula caused by button battery ingestion in a 1-year-old
      child.

PMID- 20825844
TI  - Cardiopulmonary resuscitation feedback improves the quality of chest compression
      provided by hospital health care professionals.
AB  - STUDY OBJECTIVE: High-quality chest compressions (CCs) are an important component
      of successful resuscitation. Suboptimal in-hospital CC are commonly reported.
      Skill degradation and fatigue have been implicated. We assessed the effect of a
      handheld feedback device on the measured and perceived quality of CC and rescuer
      physiologic response. METHODS: This is a nonblinded randomized controlled study
      of nurses at an academic medical center. Participants performed CC on a mannequin
      either with or without a feedback device. Compression rate (CR) and compression
      depth (CD), heart rate, and oxygen saturation were documented. Perceived quality
      of CC, fatigue, and ease of use of the device were obtained. RESULTS: Twelve
      nurses were in the feedback group (FG) and 13 were controls. Mean CD was
      significantly higher in the FG (1.99 +/- 0.37 in vs 1.52 +/- 0.36 in; P = .005)
      and mean CR significantly lower in the FG (127 +/- 13.8 per min vs 101 +/- 9.7
      per min; P <= .0001). Using a CD of more than 1.5 in and a CR of 90 to 100 as a
      composite measure of high-quality CC, the FG performed significantly better
      (81.4% +/- 22.0% vs 10.4% +/- 21.9%; P < .0001). Perceived CD, CR, and fatigue
      did not differ between groups; however, participants overestimated depth and
      underestimated rate. The FG rated the design as user-friendly (85% + 26%) helpful
      in maintaining correct CR (83% + 26%). CONCLUSION: A handheld accelerometer-based
      audiovisual cardiopulmonary resuscitation (CPR) feedback device significantly
      improved the quality of CCs provided by experienced hospital nurses in a
      simulated setting, with no perceived or measured difference in fatigue between
      the 2 groups. The CPR feedback provides an effective means to monitor and improve
      CPR performance.

PMID- 20825845
TI  - Lingual hematoma due to streptokinase in a patient with acute myocardial
      infarction.

PMID- 20825846
TI  - Usefulness of triggering receptor expressed on myeloid cells-1 in differentiating
      between typical and atypical community-acquired pneumonia.
AB  - OBJECTIVES: The purpose of this study is to investigate the clinical use of
      inflammatory marker triggering receptor expressed on myeloid cells (TREM)-1 at
      admission for differentiating between typical and atypical bacterial community
      acquired pneumonia (CAP). METHODS: A prospective, noninterventional study of
      patients with CAP hospitalized through the emergency department was performed.
      Surface expression of TREM-1 was analyzed using flow cytometry on peripheral
      blood cells, and soluble TREM-1 (sTREM-1) concentration was determined in plasma.
      RESULTS: Eighty-eight patients with clinical suspicion of CAP were eligible. The
      causative pathogen was identified in 39 patients (44.3%). After excluding 4 mixed
      pneumonia cases, 21 typical and 14 atypical bacterial infections were enrolled.
      Patients with typical bacterial CAP demonstrated increased TREM-1 surface
      expression on monocytes and neutrophils. Median plasma sTREM-1 levels at
      admission were 65.2 pg/mL (range, 17.6-138.1 pg/mL) in patients with typical CAP
      and 25.9 pg/mL (range, 11.5-54.8 pg/mL) in patients with atypical CAP (P < .001).
      Soluble TREM-1 had good discriminative value to differentiate typical from
      atypical pathogens with an area under the receiver operating characteristic curve
      of 0.87 (95% confidence interval, 0.75-0.98). At a cutoff level of 44.2 pg/mL,
      sTREM-1 yielded a sensitivity of 81%, a specificity of 79%, a positive likelihood
      ratio of 3.79, and a negative likelihood ratio of 0.24. CONCLUSIONS: In newly
      admitted patients with CAP, determination of the TREM-1 levels may provide useful
      additional diagnostic information on the bacterial etiology.

PMID- 20825847
TI  - Traumatic cervical spinal epidural hematoma mimics brachial plexus injury.

PMID- 20825848
TI  - Incidence of desaturation during prehospital rapid sequence intubation in a
      physician-based helicopter emergency service.
AB  - BACKGROUND: Hypoxemia may occur during rapid sequence intubation (RSI). This
      study establishes the incidence of this adverse event in patients intubated by
      physicians in a helicopter emergency service in Norway. METHODS: This was a
      prospective, observational study of all RSIs performed by helicopter emergency
      service physicians during a 12-month period. Hypoxemia was defined as a decrease
      in Spo(2) values to below 90% or a decrease of more than 10% if the initial
      Spo(2) was less than 90%. RESULTS: A total of 122 prehospital intubations were
      performed during the study period. Spo(2) data were available for 101 (82.8%)
      patients. Hypoxemia was present in 11 (10.9%) patients. CONCLUSIONS: Prehospital,
      RSI-related hypoxemia rates in this study are lower than reported rates in
      similar studies and are comparable with in-hospital rates. Prehospital RSI may
      accordingly be considered a safe procedure when performed by experienced
      physicians with appropriate field training.

PMID- 20825849
TI  - Incidence of tricyclic antidepressant-like complications after cyclobenzaprine
      overdose.
AB  - BACKGROUND: The cyclobenzaprine structure is similar to amitriptyline; however,
      tricyclic antidepressant (TCA)-like wide complex dysrhythmia has not been
      reported. Our objective was to determine the incidence of TCA-like effects in
      cyclobenzaprine overdoses as reported to 6 poison centers for 2 years. We
      compared the incidence of these effects to amitriptyline overdoses collected
      during the same period. METHODS: We performed a retrospective review of 2 years
      of cases as reported to the Texas Poison Center Network. We identified sole
      ingestions of cyclobenzaprine and of amitriptyline. Cases had a recorded clinical
      outcome and clinical effect. A trained reviewer used a standard data collection
      sheet within a secured electronic database. One investigator audited a random
      sample of charts. RESULTS: We identified 3974 cases of cyclobenzaprine calls. Of
      these, we collected 209 cases of acute overdoses without coingestions. There were
      no deaths. No cases of cyclobenzaprine ingestions were reported to have died or
      have a wide QRS or ventricular dysrhythmia. Seizures were reported in 2 cases;
      however, both were unrelated to cyclobenzaprine. Hypotension was reported in 1.4%
      (3/209) of cases, and a vasopressor was used in one case (0.5%). Patients with an
      amitriptyline overdose were more likely to have seizure, coma, tachycardia, a
      wide QRS or ventricular dysrhythmia, and have received sodium bicarbonate or be
      intubated. CONCLUSIONS: Cyclobenzaprine overdoses were not reported to cause
      widened QRS, ventricular dysrhythmias, or seizures, and hypotension was rarely
      reported. Tricyclic antidepressant-related effects occurred more often in our
      comparison group of amitriptyline overdoses.

PMID- 20825850
TI  - Transmission of 12-lead electrocardiographic tracings by Emergency Medical
      Technician-Basics and Emergency Medical Technician-Intermediates: a feasibility
      study.
AB  - INTRODUCTION: Prehospital transmission of the electrocardiogram (ECG) in ST
      elevation myocardial infarction patients has been shown to reduce door to
      treatment time and improve outcome. Acquisition of the ECG tracing is a paramedic
      skill, thus limiting the benefit of early ECG transmission to primarily urban
      areas. The purpose of this investigation was to determine whether prehospital
      ECGs could be transmitted by nonparamedic personnel. METHODS: A prospective case
      series of consecutive patients with a chief complaint of chest pain was
      conducted. An ECG was transmitted on all eligible patients. Proper lead placement
      was verified, and the diagnostic quality of the ECG was assessed on emergency
      department arrival. Time on scene was recorded and compared with historical
      controls. RESULTS: Ninety patients were enrolled in the study. An ECG was
      transmitted successfully in 89 (98.9%) of 90 patients. Accurate lead placement
      was noted in 89 (98.9%) of 90, and the ECG was of "diagnostic quality" in 85
      (95.5%) of 89 patients. There was no increase in scene time during the study
      period. CONCLUSION: Prehospital transmission of diagnostic-quality ECG can be
      reliably performed by nonparamedic providers.

PMID- 20825851
TI  - Submassive pulmonary embolism in a middle-age man with trivial avulsion fracture.

PMID- 20825852
TI  - Successful management of penetrating cardiac injury under guidance of
      transesophageal echocardiogram.

PMID- 20825853
TI  - Rupture of aortic aneurysm with late right hemorrhagic pleural effusion.

PMID- 20825854
TI  - Acute left-sided appendicitis with situs inversus totalis: a case report.

PMID- 20825855
TI  - Unusual metastatic localization of osteosarcoma in a teenager with ventricular
      tachycardia.

PMID- 20825856
TI  - Upstream treatment of acute coronary syndrome in the ED.
AB  - Rapid risk stratification, selection of downstream management options, and
      institution of initial pharmacotherapy are essential to ensure that patients
      admitted to the emergency department with acute coronary syndromes receive
      optimal care. A broad range of antiplatelet and antithrombotic medications is
      available that permits tailoring of initial pharmacotherapy to each patient's
      risk status. In the urgent setting, thienopyridines (clopidogrel and prasugrel)
      carry limitations including response variability and increased risk for bleeding
      in patients requiring subsequent coronary artery bypass graft surgery.
      Glycoprotein IIb-IIIa receptor inhibitors, although they are highly effective in
      preventing ischemic events, must be used with care to reduce bleeding risk.
      Bivalirudin, a relatively new direct thrombin inhibitor, represents another
      upstream option but is costly and does not have approval for this indication.
      Simplified institutional management paradigms can streamline the process of
      selecting appropriate pharmacotherapy and aid in care delivery that will optimize
      patient outcomes.

PMID- 20825857
TI  - An uncommonly recognized cause of rhabdomyolysis after quetiapine intoxication.

PMID- 20825858
TI  - Posterior comminuted scapular fracture induced by a low-voltage electric shock.

PMID- 20825859
TI  - Aortic dissection presenting as isolated lower extremity pain in a young man.

PMID- 20825860
TI  - Allergic angina can be determined by the early use of cardiac magnetic resonance
      imaging.

PMID- 20825861
TI  - Emergent precordial percussion revisited--pacing the heart in asystole.
AB  - Precordial percussion is a technique by which a manual force is applied
      repeatedly to the chest of a patient experiencing an unstable bradycardic or
      asystolic rhythm. The force is used not to defibrillate the myocardium as is the
      case with the "precordial thump" in pulseless ventricular tachycardia/ventricular
      fibrillation but rather to initiate a current through the myocardium in the form
      of an essentially mechanically paced beat. In this review, we discuss the
      physiology and utility of precordial percussion, or precordial thump, in the
      emergency setting as a very temporary bridge to more effective and permanent
      pacing techniques.

PMID- 20825862
TI  - Acute life-threatening presentation of unknown lymphatic malformation.

PMID- 20825863
TI  - Fatal hyperhemolytic delayed transfusion reaction in sickle cell disease: a case
      report and literature review.

PMID- 20825864
TI  - Pulmonary capillary leak syndrome after influenza A (H1N1) virus infection.

PMID- 20825865
TI  - Aortic dissection presenting as left leg numbness and paralysis.

PMID- 20825866
TI  - Suicide by Duragesic transdermal fentanyl patch toxicity.

PMID- 20825867
TI  - Cannabis-induced acute pancreatitis.

PMID- 20825868
TI  - Accelerated management of patients with ST-segment elevation myocardial
      infarction in the ED.
AB  - PURPOSES: The objective of this study was to evaluate improvement opportunities
      in the emergency department for timely ST-segment elevation myocardial infarction
      management and evaluated the new process flow. BASIC PROCEDURES: In a prospective
      study, we compared time from door to cath laboratory before and after
      implementation of a new ST-segment elevation myocardial infarction (STEMI)
      protocol. The new protocol included a blend of strategies to reduce door to cath
      laboratory time. MAIN FINDINGS: We included 55 patients. After implementing a new
      STEMI protocol, we included 54 patients. Time to cath laboratory was 21
      (interquartile range, 9-40) minutes before and 10 (interquartile range 5-25)
      minutes after initiation of the new protocol (P = .02). A door to cath laboratory
      time less than 15 minutes was reached in 36% of our patients in phase 1 and in
      61% in phase 2 (odds ratio; 0.36, 95% confidence interval, 0.16-0.81; P = .01).
      PRINCIPAL CONCLUSION: Simple changes in organizational strategies resulted in a
      significantly faster care for patients with acute uncomplicated STEMI.

PMID- 20825869
TI  - Right lower quadrant pain in an adult woman.

PMID- 20825870
TI  - Abdominal compressions do not achieve similar survival rates compared with chest
      compressions: an experimental study.
AB  - AIM: The aim of this study is to investigate whether abdominal compression
      cardiopulmonary resuscitation (CPR) would result in similar survival rates and
      neurologic outcome than chest compression CPR in a swine model of cardiac arrest.
      MATERIALS AND METHODS: Forty Landrace/Large White piglets were randomized into 2
      groups: group A (n = 20) was resuscitated using chest compression CPR, and group
      B (n = 20) was resuscitated with abdominal compression CPR. Ventricular
      fibrillation was induced with a pacemaker catheter, and animals were left
      untreated for 8 minutes. Abdominal and chest compressions were applied with a
      mechanical compressor. Defibrillation was then attempted. RESULTS: Neuron
      specific enolase and S-100 levels were significantly higher in group B. Ten
      animals survived for 24 hours in group A in contrast to only 3 animals in group B
      (P < .05). Neurologic alertness score was worse in group B compared with group A.
      CONCLUSION: Abdominal compression CPR does not improve survival and neurologic
      outcome in this swine model of cardiac arrest and CPR.

PMID- 20825871
TI  - Serum troponin testing in patients with paroxysmal supraventricular tachycardia:
      outcome after ED care.
AB  - Paroxysmal supraventricular tachycardia (PSVT), a common dysrhythmia seen in the
      emergency department (ED), is usually managed without difficulty and with a
      favorable prognosis. Serum cardiac troponin I (cTnI) testing provides important
      risk stratification information in certain patients; its use in PSVT patients,
      however, has not been explored. A retrospective review of consecutive adult ED
      PSVT patients seen for 21 months was performed. Fifty-four PSVT patients were
      identified on the basis of International Classification of Disease, Ninth Edition
      codes and the ED patient log at a university hospital. Three patients were
      excluded for incorrect rhythm, leaving 51 who were included in data analysis.
      Thirty-eight patients had at least one serum cTnI value measured. Of those, 11
      had a positive result, defined as serum cTnI of more than 0.02 ng/dL. Thirty-day
      outcomes for these patients were evaluated and showed one ED return, no PSVT
      recurrences, and no deaths at our regional hospital. In this sample, serum cTnI
      testing did not identify PSVT patients at risk for poor outcome. Further
      consideration of the use of this testing modality in the PSVT patient population
      is recommended.

PMID- 20825872
TI  - Impact of positive end-expiratory pressure on cerebral injury patients with
      hypoxemia.
AB  - BACKGROUND: Traumatic brain injury or intracranial hemorrhage patients with acute
      lung injury/acute respiratory distress syndrome need mechanical ventilation. The
      use of positive end-expiratory pressure (PEEP) in this situation remains
      controversial. This study explored the impact of PEEP on intracranial pressure
      (ICP), cerebral perfusion pressure (CPP), central venous pressure (CVP), and mean
      arterial pressure (MAP) in cerebral injury patients. METHODS: Nine cerebral
      injury patients with lung injury who needed mechanical ventilation and met the
      criteria for ICP monitoring were included in this study. Intraventricular
      catheters were positioned in 1 of the bilateral ventricles and connected to
      pressure transducers. Invasive arterial pressure and CVP were monitored
      continuously. Pressure control ventilation was applied during this clinical trial
      in a stepwise recruitment maneuver (RM) with 3 cm H2O intermittent increments and
      decrements of PEEP. RESULTS: A total of 28 RMs were completed in 9 patients. Mean
      values of MAP, CVP, ICP, and CPP 5 minutes after RMs showed no significant
      differences compared with baseline (P > 0.05). Correlation analysis of all the
      mean values of MAP, CVP, ICP, and CPP showed significant correlation between MAP
      and CPP, PEEP and CVP, PEEP and ICP, and PEEP and CPP with all P values less than
      0.05. CONCLUSION: The impact of PEEP on blood pressure, ICP, and CPP varies
      greatly in cerebral injury patients. Mean arterial pressure and ICP monitoring is
      of benefit when using PEEP in cerebral injury patients with hypoxemia.

PMID- 20825873
TI  - Abdominal pain in the ED: a 35 year retrospective.
AB  - OBJECTIVE: Research published in 1972 and 1993 has detailed the demographics,
      diagnoses, and diagnostic test utilization of adult patients presenting with
      nontraumatic abdominal pain to the emergency department (ED) at the University of
      Virginia Hospital. This is an update of those studies, designed to examine the
      present state of diagnosis and management of abdominal pain, as well as to look
      at trends during the 35-year span of the investigations. METHODS: One thousand
      consecutive adult patients presenting in the year 2007 with abdominal pain as
      their chief complaint were included in the analysis. Demographic data, discharge
      diagnosis, disposition, ED length of stay, charges, and diagnostic test
      utilization information were gathered and analyzed using electronic databases.
      RESULTS: These patients represented 6.5% of the total ED census. Sixty-five
      percent were female, 24.7% hospitalized, and 21% diagnosed with undifferentiated
      abdominal pain. Relative to 1993, there were more patients receiving specific
      diagnoses, (79% versus 75%) and a higher rate of hospitalization (24.7% versus
      18.3%). Use of diagnostic testing has markedly increased in frequency, most
      notably computed tomography and ultrasound, which have risen 6-fold. One of these
      imaging modalities is now used in 42% of patient encounters. Visit times were
      longer and patient charges higher. There were 2 cases of missed surgical disease
      in 2007 compared with 1 in 1993 and 8 in 1972. CONCLUSION: Over the past 35
      years, ED management of atraumatic abdominal pain has become time, money, and
      resource intense. Widespread use of sophisticated imaging has had a small impact
      on diagnostic specificity but has not produced lower admission rates or fewer
      cases of missed surgical illness.

PMID- 20825874
TI  - Tetanus Quick Stick as an applicable and cost-effective test in assessment of
      immunity status.
AB  - INTRODUCTION: Tetanus vaccine and immunoglobulin administration are challenging
      decisions mostly because of the fact that the current protocol for immunization
      against tetanus is based on 2 variables: the vaccination status of the patient
      and the nature of wound and its exposure. To solve this problem, Tetanus Quick
      Stick (TQS; Nephrotek Laboratory, Rungis, France), an immunochromatographic
      dipstick test, was developed to determine the tetanus immunity of the patients.
      The aim of this present study was to investigate the sensitivity, specificity,
      and the positive and negative predictive values and cost-effectiveness of TQS in
      the emergency department (ED) setting. METHODS: Blood samples were collected from
      200 patients presenting to our ED. Information including demographic information,
      tetanus immunization status, wound description, and the preventive measures taken
      by the emergency physician were gathered by a preeducated nurse. Tetanus Quick
      Stick test and enzyme-linked immunosorbent assay were performed as the standard
      diagnostic test by an emergency physician and a laboratory technician,
      respectively; and results of the 2 techniques were compared. RESULT: Overall,
      tetanus vaccine was administered to 141(70.5%) patients and immunoglobulin to 105
      (52.5%) patients. The analysis revealed 88.1% sensitivity and 97.6% specificity
      for the TQS test. The positive and negative predictive values of TQS test were
      99.3% and 66.1%, respectively. Our analysis is also showed a significant decrease
      in cost when TQS was applied for patients with dirty, tetanus prone wounds or
      injuries and unknown or incomplete vaccination history (? 9.48 versus ? 12.1).
      CONCLUSION: This study revealed TQS test to be appropriate and cost-effective for
      ED use especially in evaluating patients who do not remember or cannot give their
      tetanus immunization history.

PMID- 20825875
TI  - The role of emergency ultrasound for evaluating acute pyelonephritis in the ED.
AB  - BACKGROUND: Controversy remains over the imaging method of choice for evaluating
      acute pyelonephritis (APN) in the emergency department (ED). OBJECTIVE: The aim
      of the study was to determine the efficacy of ultrasound in the diagnosis and
      management of patients presented to the ED with APN. METHODS: This was a
      retrospective study of prospectively collected data. A cohort of ED patients
      diagnosed as APN were prospectively registered, and their medical records were
      then retrospectively reviewed for the presence of complications (admitted >14
      days, admission to intensive care unit, or received invasive procedures),
      significant abnormalities (hydronephrosis, polycystic kidney diseases, renal
      abscess, emphysematous pyelonephritis), and mild abnormalities (cysts, stones,
      swelling). RESULTS: The study included 243 patients. Most of the patients
      received one or more renal imaging studies (n = 206) and 39.5% of which were
      considered abnormal. The rates of significant abnormalities on different imaging
      methods were Kidney-ureter-bladder (KUB), 16.3%; emergency ultrasound (EUS),
      39.6%; combination of KUB and EUS, 56.6%; and computed tomography, 58.8%. Factors
      contributed to complicated APN were elderly, male, a history of preexisting renal
      diseases, current use of catheters, previous renal calculi, and diabetes
      mellitus. Significant abnormalities can be identified by EUS in 61% of patients
      with complicated APN. In fact, the presence of significant sonographic
      abnormalities effectively diverted 34.3% of patients to receive surgical
      interventions (percutaneous nephrostomy, abscess aspiration, ureteroscopic stone
      manipulation, lithotripsy, or nephrectomy). CONCLUSION: Structural abnormalities
      are not uncommon in ED patients with APN. Early assessment of these patients with
      EUS is likely to have a great impact on their diagnosis and management.

PMID- 20825876
TI  - Evaluation of 2 different instruments for exposing the chest in conjunction with
      a cardiac arrest.
AB  - BACKGROUND: Time between onset of cardiac arrest and start of treatment is of
      ultimate importance for outcome. The length of time it takes to expose the chest
      in out-of-hospital cardiac arrest (OHCA) is not known. We aimed to compare the
      time from onset of OHCA until the time at which the chest was exposed using a new
      device (S-CUT; ES Equipment, Gothenburg, Sweden) and a pair of scissors. METHODS:
      In a manikin study, the 2 devices were compared in a simulated cardiac arrest
      where the initial step was exposure of the chest. The tests were performed using
      ambulance staff from 3 different ambulance organizations in Western Sweden. Six
      different types of clothing combinations were used. The primary choices of
      clothing for analyses were a knitted sweater and shirt (indoors) and a jacket
      with buttons, a shirt, and a college sweater (outdoors). RESULTS: The mean
      difference from onset of OHCA until the chest was exposed when S-CUT was compared
      with a pair of scissors varied between 6 seconds (P = .006) and 63 seconds (P =
      .004; shorter with the S-CUT), depending on the type of clothing that was used.
      The mean differences for the clothing that was chosen for primary analyses were
      23 and 63 seconds, respectively. CONCLUSION: We found that a new device (S-CUT)
      used for exposing the chest in OHCA was associated with a marked shortening of
      procedure time as compared with a pair of scissors.

PMID- 20825877
TI  - Successful treatment of presumed massive pulmonary embolism during cardiac
      arrest.

PMID- 20825878
TI  - Flow resistance, work of breathing of humidifiers, and endotracheal tubes in the
      hyperbaric chamber.
AB  - Humidification of inspired gas is critical in ventilated patients, usually
      achieved by heat and moisture exchange devices (HMEs). HME and the endotracheal
      tube (ETT) add airflow resistance. Ventilated patients are sometimes treated in
      hyperbaric chambers. Increased gas density may increase total airway resistance,
      peak pressures (PPs), and mechanical work of breathing (WOB). We tested the added
      WOB imposed by HMEs and various sizes of ETT under hyperbaric conditions. We
      mechanically ventilated 4 types of HMEs and 3 ETTs at 6 minute ventilation
      volumes (7-19.5 L/min) in a hyperbaric chamber at pressures of 1 to 6 atmospheres
      absolute (ATA). Peak pressure increased with increasing chamber pressure with an
      HME alone, from 2 cm H2O at 1 ATA to 6 cm H(2)O at 6 ATA. Work of breathing was
      low at 1 ATA (0.2 J/L) and increased to 1.2 J/L at 6 ATA at minute ventilation =
      19.5 L/min. Connecting the HME to an ETT increased PP as a function of peak flow
      and chamber pressure. Reduction of the ETT diameter (9 > 8 > 7.5 mm) and increase
      in chamber pressure increased the PP up to 27.7 cm H2O, resistance to 33.2
      cmH2O*s/L, and WOB to 3.76 J/L at 6 ATA with a 7.5-mm EET. These are much greater
      than the usually accepted critical peak pressures of 25 cm H2O and WOB of 1.5 to
      2.0 J/L. Endotracheal tubes less than 8 mm produce significant added WOB and
      airway pressure swings under hyperbaric conditions. The hyperbaric critical care
      clinician is advised to use the largest possible ETT. The tested HMEs add
      negligible resistance and WOB in the chamber.

PMID- 20825879
TI  - Resuscitation with balanced electrolyte solution prevents hyperchloremic
      metabolic acidosis in patients with diabetic ketoacidosis.
AB  - OBJECTIVE: The objective of the study was to determine if balanced electrolyte
      solution (BES) prevents hyperchloremic metabolic acidosis in patients with
      diabetic ketoacidosis (DKA). METHODS: This is a prospective, randomized, double
      blind study. A convenience sample of DKA patients aged 18 to 65 years with serum
      bicarbonate less than or equal to 15 and anion gap greater than or equal to 16
      was enrolled at "Louisiana State University Health Sciences Center-Shreveport" an
      capitalize Emergency Department over a 24-month period (2006-2008). Patients were
      randomized to standardized resuscitation with normal saline (NS) or BES (Plasma
      Lyte A pH 7.4; Baxter International, Deerfield, IL). Every 2 hours, serum
      chloride and bicarbonate were measured until the patient's anion gap decreased to
      12. An intention-to-treat analysis was performed on patients who met inclusion
      criteria and received at least 4 hours of study fluid. Chloride and bicarbonate
      measurements from the BES and NS groups were compared using unpaired and paired
      Student t tests. RESULTS: Of 52 patients enrolled, 45 (22 in BES group and 23 in
      NS group) met inclusion criteria and received 4 hours of fluid. The mean
      postresuscitation chloride was 111 mmol/L (95% confidence interval [CI] = 110
      112) in the NS group and 105 mmol/L (95% CI = 103-108) in the BES group (P <=
      .001). The mean postresuscitation bicarbonate was 17 mmol/L (95% CI = 15-18) in
      the NS group and 20 mmol/L (95% CI = 18-21) in the BES group (P = .020).
      CONCLUSIONS: Resuscitation of DKA patients with BES results in lower serum
      chloride and higher bicarbonate levels than patients receiving NS, consistent
      with prevention of hyperchloremic metabolic acidosis.

PMID- 20825880
TI  - Effects of norepinephrine on kidney in a swine model of cardiopulmonary
      resuscitation.
AB  - BACKGROUND: The aim of this study was to study the effects of norepinephrine (NE)
      induced hypertension (HT) on renal biochemistry, enzymology, and morphology after
      restoration of spontaneous circulation (ROSC) by cardiopulmonary resuscitation
      (CPR) in swine. METHODS: After 4 minutes of ventricular fibrillation, standard
      CPR was carried out. The survivors were then divided into 2 groups. The HT group
      (n = 5) received 0.4 to 1.0 MUg kg-1 min-1 of NE continuously to maintain the
      mean arterial pressure (MAP) at 130% of the baseline (ie, MAP before ventricular
      fibrillation). The normal pressure (NP) group (n = 5) received 0.2 to 0.5 MUg kg
      1 min-1 NE continuously to maintain MAP at the baseline level. Hemodynamic status
      and oxygen metabolism were monitored, and blood urea nitrogen and creatinine were
      measured in blood samples obtained at baseline and at 10 minutes, 2 and 4 hours
      after ROSC. At 24 hours after ROSC, the animals were killed and the kidney was
      removed to determine Na+-K+-ATPase and Ca2+-ATPase activities and histologic
      changes under a light and electron microscopy. RESULTS: mean arterial pressure,
      cardiac output, and coronary perfusion pressure were significantly higher (P <
      .01), whereas the oxygen extraction ratio was lower in the HT group than in the
      NP group (P < .05). Blood urea nitrogen and creatinine increased in the NP group
      but did not change in the HT group. Renal ATP enzyme activity was significantly
      higher in the HT group than the NP group (Na+-K+-ATP enzyme: 4.024 +/- 0.740 U
      versus 3.190 +/- 0.789 U, Ca2+-ATP enzyme: 3.615 +/- 0.668 versus 2.630 +/-
      0.816; both P < .05). The HT group showed less cellular edema, necrosis, and
      fewer damaged mitochondria compared with the NP group. CONCLUSION: These data
      suggest that inducing HT by NE helps to maintain stable hemodynamic status and
      oxygen metabolism and may protect the kidney in terms of biochemistry,
      enzymology, and histology after CPR.

PMID- 20825882
TI  - Infectious spondylodiscitis presenting with abdominal pain in the ED.

PMID- 20825881
TI  - Ischemia-modified albumin levels in carbon monoxide poisoning.
AB  - OBJECTIVES: Ischemia-modified albumin (IMA) is an emerging diagnostic biomarker
      for many ischemic conditions. This study was conducted to investigate whether
      there is a change in IMA levels in carbon monoxide (CO) poisoning and, if so, the
      clinical relevance of IMA levels. METHODS: This cohort study, performed between
      November 2008 and April 2009, compared the serum IMA levels of 33 CO-poisoned
      patients taken at the time of presentation at the emergency department and after
      3 hours of treatment and 49 healthy controls. In addition, IMA and
      carboxyhemoglobin levels were analyzed according to CO poisoning patients'
      poisoning severity scores. RESULTS: Carbon monoxide patients' IMA levels were
      higher than those of the control group both at time of admission and at the third
      hour of the treatment, P < .0001. A significant fall was determined in
      carboxyhemoglobin (CO-Hb) levels at the end of the third hour of treatment, P <
      .0001. However, there was no significant difference between the IMA levels
      measured at admission and at the end of the third hour of treatment (P > .05).
      There was no significant correlation between IMA and CO-Hb levels in CO-poisoned
      patients. Also, there was no difference in blood IMA levels in classification
      according to patients' poisoning severity score and CO-Hb levels. CONCLUSION:
      Results from this pioneering study established a high level of IMA in CO-poisoned
      patients, suggesting that IMA may also be sensitive to hypoxia. Considering the
      preliminary nature of this study, the clinical utility of IMA levels in CO
      poisoning should be further investigated with more comprehensive studies.

PMID- 20825883
TI  - Mollaret meningitis: case report with a familial association.
AB  - Mollaret meningitis is a syndrome characterized by recurrent bouts of meningitis
      that occur over a period of several years in an affected patient. Also known as
      recurrent lymphocytic meningitis, this entity involves repeated episodes of
      headache, stiff neck, fever, and cerebrospinal fluid pleocytosis. Herpes simplex
      virus type 2 is the most frequently implicated causative agent, and treatment
      involves the use of antiviral medications. We describe a case of Mollaret
      meningitis in a 47-year-old man who presented to the emergency department with
      his eighth episode of meningitis during a period of 20 years. Cerebrospinal fluid
      polymerase chain reaction testing for herpes simplex virus type 2 was positive,
      and further testing excluded other common viral, bacterial, and inflammatory
      causes of meningeal irritation. The patient's family history was significant for
      a brother who also had multiple episodes of aseptic meningitis during a period of
      several years. This represents the first published report of a possible familial
      association involving Mollaret meningitis. It is likely that Mollaret meningitis
      is underrecognized among emergency physicians, and improved recognition of this
      entity may limit unwarranted antibiotic use and shorten or eliminate unnecessary
      hospital admission.

PMID- 20825884
TI  - Terlipressin saved the life of a child with severe nonvariceal upper
      gastrointestinal bleeding.

PMID- 20825885
TI  - A peculiar medical cardioversion of atrial fibrillation with glucose infusion--a
      rare cause of atrial fibrillation: hypoglycemia.

PMID- 20825886
TI  - Acute respiratory distress as an initial presentation of acute aortic occlusion.

PMID- 20825888
TI  - Opioid toxicity as a cause of spontaneous urinary bladder rupture.

PMID- 20825887
TI  - Tracheal intubation using Macintosh and 2 video laryngoscopes with and without
      chest compressions.
AB  - PURPOSE: The aim of the study was to compare the time taken for intubation (TTI)
      using the Macintosh and 2 video laryngoscopes (VLs) (GlideScope [GVL]; Saturn
      Biomedical System, Burnaby, British Columbia, Canada, and Airway Scope [AWS];
      Pentax, Tokyo, Japan) with and without chest compressions by experienced
      intubators in a mannequin model. METHODS: This was a randomized crossover study.
      Twenty-two experienced physicians who have limited experience in the VLs
      participated in the study. The TTI using 3 laryngoscopes with and without
      compressions were compared. RESULTS: Median TTI difference between 2 conditions
      was only significant in the AWS (1.64 seconds; P = .01). There were no
      significant differences in the TTI between the Macintosh and the GVL or the AWS
      during compressions. CONCLUSION: In a mannequin model, the Macintosh or the GVL
      was not affected by chest compressions. The TTI using the AWS was delayed by
      compressions but not clinically significant. Considering the lack of experience,
      2 VLs may be useful adjuncts for intubation by experienced intubators during
      chest compressions.

PMID- 20825889
TI  - Do we need echocardiography before commencing thrombolytic therapy?
AB  - We report a case of a 41-year-old man who had fatal multiple cerebral and
      bilateral renal infarcts 1 hour after initiation of thrombolytic therapy for
      acute ST elevation myocardial infarction. Echocardiography study disclosed
      dilated left ventricle with severe global hypokinesia suggestive of preexisting
      cardiomyopathy and a disintegrated left ventricular apical thrombus pointing out
      to the source of the embolic complication. This raises the question whether
      echocardiography before initiating thrombolytic therapy would affect the decision
      of commencing thrombolytic therapy and help avoiding such lethal embolic
      complications.

PMID- 20825890
TI  - Prophylactic fluid therapy in crushed victims of Bam earthquake.
AB  - BACKGROUND: Acute kidney injury (AKI) is a severe and preventable problem of
      crushed earthquake victims. Early hydration therapy started before fully removing
      earthquake rubbles has been claimed to play a decisive role in AKI prevention,
      which saves the necessity of later dialysis. However, the extent, quality, and
      appropriateness of its know-how are controversial. METHODS: Processing clinical
      and paraclinical data gathered from Bam earthquake victims older than 15 years,
      we tried to determine correlations between the time of being under the rubbles
      (TUR), the level of serum creatine phosphokinase (CPK), the delayed onset of
      fluid therapy (DFT), and finally the volume of intravenous fluid received per day
      (VFR) with the formation of AKI and the need for dialysis. RESULTS: There is a
      direct and significant relation between the intensity of the trauma (TUR and CPK)
      and DFT with the occurrence of AKI and need for dialysis (P < .001). However, as
      the VFR increases, the occurrence of AKI and the need for dialysis significantly
      decrease (P = .005). Based on multivariate analysis, the occurrence of AKI and
      the need for dialysis are primarily affected by CPK, TUR, and VFR; and DFT has
      been dropped out. The analysis showed the preventive role of VFR more than 6 L in
      severe rhabdomyolysis patients and of at least 3 L in moderate ones in
      development of AKI and dialysis. CONCLUSIONS: In the severely rhabdomyolized
      patients (CPK >= 15,000), higher volumes of prophylactic fluid (VFR >6 L) are
      required, whereas in less-traumatized patients, lower volumes (3-6 L) would be
      effective.

PMID- 20825891
TI  - Unexplained chest pain in the ED: could it be panic?
AB  - PURPOSE: This study aimed at (1) establishing the prevalence of paniclike anxiety
      in emergency department (ED) patients with unexplained chest pain (UCP); (2)
      describing and comparing the sociodemographic, medical, and psychiatric
      characteristics of UCP patients with and without paniclike anxiety; and (3)
      measuring the rate of identification of panic in this population. BASIC
      PROCEDURE: A structured interview, the Anxiety Disorders Interview Schedule for
      the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, was
      administered to identify paniclike anxiety and evaluate patients' psychiatric
      status. Anxious and depressive symptoms were evaluated with self-report
      questionnaires. Medical information was extracted from patients' medical records.
      MAIN FINDINGS: The prevalence of paniclike anxiety was 44% (95% CI, 40%-48%) in
      the sample (n = 771). Psychiatric disorders were more common in panic patients
      (63.4% vs 20.1%), as were suicidal thoughts (21.3% vs 11.3%). Emergency physician
      diagnosed only 7.4% of panic cases. PRINCIPAL CONCLUSIONS: Paniclike anxiety is
      common in ED patients with UCP, and this condition is rarely diagnosed in this
      population.

PMID- 20825892
TI  - Racial disparity in analgesic treatment for ED patients with abdominal or back
      pain.
AB  - OBJECTIVE: Research on how race affects access to analgesia in the emergency
      department (ED) has yielded conflicting results. We assessed whether patient race
      affects analgesia administration for patients presenting with back or abdominal
      pain. METHODS: This is a retrospective cohort study of adults who presented to 2
      urban EDs with back or abdominal pain for a 4-year period. To assess differences
      in analgesia administration and time to analgesia between races, Fisher exact and
      Wilcoxon rank sum test were used, respectively. Relative risk regression was used
      to adjust for potential confounders. RESULTS: Of 20,125 patients included (mean
      age, 42 years; 64% female; 75% black; mean pain score, 7.5), 6218 (31%) had back
      pain and 13,907 (69%) abdominal pain. Overall, 12,109 patients (60%) received any
      analgesia and 8475 (42%) received opiates. Comparing nonwhite (77 %) to white
      patients (23%), nonwhites were more likely to report severe pain (pain score, 9
      10) (42% vs 36%; P < .0001) yet less likely to receive any analgesia (59% vs 66%;
      P < .0001) and less likely to receive an opiate (39% vs 51%; P < .0001). After
      controlling for age, sex, presenting complaint, triage class, admission, and
      severe pain, white patients were still 10% more likely to receive opiates
      (relative risk, 1.10; 95% confidence interval, 1.06-1.13). Of patients who
      received analgesia, nonwhites waited longer for opiate analgesia (median time, 98
      vs 90 minutes; P = .004). CONCLUSIONS: After controlling for potential
      confounders, nonwhite patients who presented to the ED for abdominal or back pain
      were less likely than whites to receive analgesia and waited longer for their
      opiate medication.

PMID- 20825893
TI  - Mydriatic pupil as the presenting sign of aortic dissection.

PMID- 20825894
TI  - Splenic rupture after colonoscopy.

PMID- 20825895
TI  - Natriuretic peptide testing in EDs for managing acute dyspnea: a meta-analysis.
AB  - PURPOSES: The aim of the study was to assess the usefulness of systematic
      natriuretic peptide testing in the management of patients presenting with acute
      dyspnea to emergency departments (EDs). METHODS: We performed a systematic review
      and meta-analysis of randomized controlled trials assessing the usefulness of B
      type natriuretic peptide (BNP) or its N-terminal fragment (NT-proBNP) in the
      management of patients presenting with dyspnea into ED. We searched Medline,
      Embase, and conference proceedings without restriction on neither language nor
      publication year. Selection of studies, data collection, and assessment of risk
      of bias were performed by 2 reviewers independently and in duplicate. Outcomes
      included hospital admission rate, time to discharge, and length of hospital stay,
      mortality and rehospitalization rates, and total direct medical costs. Combined
      risk ratios were estimated using fixed or random effects model. Duration and cost
      data were not combined. FINDINGS: Four randomized controlled trials, representing
      2041 patients, were selected. In 4 trials, there was a tendency for hospital
      admission to be reduced in the intervention group (combined risk ratio, 0.95; 95%
      confidence interval, 0.89-1.01). Time to discharge was significantly reduced in 2
      trials, whereas there was no significant reduction in hospital length of stay in
      3 trials. There was no significant effect on in-hospital and 30-day mortality
      rates or rehospitalization rates (3 trials reporting each outcome). Two trials
      found significant reduction in direct costs. CONCLUSIONS: The current evidence
      remains inconclusive on whether systematic natriuretic peptide testing is useful
      for the management of patients presenting to ED with acute dyspnea.

PMID- 20825896
TI  - The seasonality of acute coronary syndrome and its relations with climatic
      parameters.
AB  - BACKGROUND: Most research on the seasonality of acute coronary syndrome (ACS) has
      been were reported from hospital-based data. We aimed to investigate the seasonal
      distribution of ACS in Beijing and to elucidate the relations between ACS
      occurrence and climatic parameters in a prehospital setting. METHODS: We
      retrospectively reviewed the electronic prehospital medical records from the
      Beijing's emergency medical service system spanning August 1, 2005, to July 31,
      2007. Case data were analyzed by month and season with chi2 test. The effects of
      climatic factors on the occurrence of ACS were analyzed by Poisson regression
      with generalized linear model. RESULTS: During the 2-year study period, a total
      of 7037 ACS events were identified, including 4135 male patients (58.8%) and 2902
      female patients (41.2%). Significant variations were observed in the monthly (P <
      .001) and seasonal (P < .001) distribution of ACS. The highest seasonal incidence
      occurred in winter and lowest in autumn. Significant negative correlations were
      noticed between the number of ACS events and daily mean temperature (P < .001)
      and between the number of ACS events and barometric pressure (P < .001).
      Comparing to the baseline level (temperature of 25 degrees C to approximately 31
      degrees C; barometric pressure of 1026 to approximately 1048 hectopascal (hPa)),
      an increase of 41.3% of daily ACS incidence was associated with temperature lower
      than 2 degrees C (-10.0 degrees C to approximately 2.0 degrees C), and an
      increase of 19.8% was associated with barometric pressure under 1006 hPa (991.0
      to approximately 1006 hPa). CONCLUSIONS: There are clear monthly and seasonal
      rhythms of ACS in Beijing metropolitan area. Temperature and barometric pressure
      are negatively related with the occurrence of ACS.

PMID- 20825897
TI  - Pulmonary tumor thrombotic microangiopathy.

PMID- 20825898
TI  - Comparison of bedside ultrasound and panorex radiography in the diagnosis of a
      dental abscess in the ED.
AB  - OBJECTIVE: The purpose of the study was to compare bedside ultrasound (US) and
      panorex radiography in the diagnosis of a dental abscess in emergency department
      (ED). METHODS: A retrospective review of ED records of adult patients with
      atraumatic facial pain, swelling, and toothache who received a panorex x-ray and
      bedside US was performed. Medical records were reviewed for ED evaluation and
      disposition. Sensitivity and specificity of US and panorex x-ray were calculated
      to determine the clinical utility of the 2 tests. RESULTS: A total of 19 patients
      were identified. No periapical abscess was reported on panorex x-rays in 7 (37%)
      of 19 patients. Ultrasound agreed with panorex x-rays in 6 (86%) of 7 cases. One
      case where US disagreed with x-rays was evaluated by dentistry consultants; and
      incision and drainage were performed, confirming the presence of an abscess. An x
      ray diagnosis of periapical abscess was made in 12 (63%) of 19 patients.
      Ultrasound agreed with panorex x-ray in 10 (83%) of 12 cases. In 1 of the 2 cases
      where US disagreed with panorex x-rays, x-ray abnormalities were reported on the
      nonsymptomatic side. The other patient was given antibiotics and recommended
      outpatient follow-up. Follow-up information was not available to further confirm
      the presence of an abscess. Assuming that the patient who was lost to follow-up
      had dental abscess, the sensitivity and specificity of US in diagnosing a dental
      abscess were 92% and 100%, respectively. CONCLUSIONS: Bedside US is nonionizing,
      is readily available, and can provide an alternative to panorex x-rays in the
      evaluation of a dental abscess in ED.

PMID- 20825899
TI  - Recovery of paralysis in association with an improvement of hypomagnesemia due to
      alcoholism.

PMID- 20825900
TI  - Trimethoprim-sulfamethoxazole-induced aseptic meningitis.

PMID- 20825901
TI  - Continuous positive airway pressure for cardiogenic pulmonary edema: a randomized
      study.
AB  - STUDY OBJECTIVE: The purpose of this randomized controlled trial was to determine
      the immediate and delayed effects of noninvasive ventilation for patients in
      acute cardiogenic pulmonary edema (ACPE) in addition to aggressive usual care in
      a medical prehospital setting. METHODS: Out-of-hospital patients in severe ACPE
      were eligible for the study. Patients were randomized to receive either usual
      care, including conventional optimal treatment with furosemide, oxygen, and high
      dose boluses of isosorbide dinitrate plus oxygen, or conventional medications
      plus out-of-hospital continuous positive airway pressure (CPAP). The primary
      outcome was the treatment success defined as all of respiratory rate less than 25
      breaths per minute and oxygen saturation of greater than 90% at the end of 1-hour
      study. Secondary end points included death during 30 days after inclusion.
      Lengths of intensive care unit and hospital stays were also recorded. RESULTS: In
      total, 124 patients were enrolled into the study. The 2 groups had similar
      baseline characteristics. For the primary outcome analysis, 22 (35.5%) of 62
      patients were considered as experiencing a treatment success in the usual care
      group vs 19 (31.7%) of 60 in the CPAP group (P = .65). Seven patients died within
      30 days in the usual care group vs 6 in the CPAP group (P = .52). There were no
      statistically significant differences between the treatment groups for length of
      stay either in hospital or in the intensive care unit. CONCLUSION: In the
      prehospital setting, in spite of its potential advantages for patients in ACPE,
      CPAP may not be preferred to a strict optimal intravenous treatment.

PMID- 20825902
TI  - Nephrotic syndrome complicated with acute mesenteric ischemia.

PMID- 20825903
TI  - Automated electroencephalogram identifies abnormalities in the ED.
AB  - BACKGROUND: Advances in analysis of electrical signals have now made it possible
      to create a handheld electroencephalogram (EEG). METHODS: The BrainScope device,
      currently under development by BrainScope Co, Inc, Washington, DC, was used to
      assess 153 patients who presented to a tertiary referral hospital with headache
      or altered mental status. A limited array of 8 adhesive electrodes, similar to
      electrocardiographic leads, was applied to the forehead of the subjects. The data
      were analyzed, and the result given by the algorithm was compared with the
      clinical diagnosis given to the patient. RESULTS: One hundred fifty-three
      patients were enrolled. The patient was determined to be normal or abnormal using
      the algorithm in the device, and blinded clinicians determined whether this was
      accurate. The sensitivity of the device was 96% and the specificity was 87% for
      detecting abnormality. CONCLUSIONS: The automated EEG device may be a useful tool
      for identifying brain abnormality in the emergency department.

PMID- 20825904
TI  - A case report of Stanford type A aortic dissection presenting with status
      epilepticus.

PMID- 20825905
TI  - The efficacy of obidoxime 72 hours after intoxication by organophosphates.

PMID- 20825906
TI  - Immune reconstitution syndrome-induced hypercalcemic crisis.

PMID- 20825907
TI  - Repolarization abnormalities with cocaine: need for enhanced vigilance.

PMID- 20825908
TI  - Diagnosis of intussusception using point-of-care ultrasound in the pediatric ED:
      a case report.

PMID- 20825909
TI  - Acute hip pain and inability to ambulate: a rare presentation for perirectal
      abscess.
AB  - A patient with acute hip pain out of proportion to physical findings and
      inability to weight bear despite negative plain films warrants further in-depth
      evaluation. Correctly diagnosing the cause of hip pain, a common emergency
      department (ED) complaint, may be a challenge in the geriatric population (Perron
      A, Miller M, Brady W. Orthopedic pitfalls in the ED: radiographically occult hip
      fracture. Am J Emerg Med 2002; 20: 234-7; Cannon J, Silvestri S, Munro M. Imaging
      choices in occult hip fracture. J Emerg Med 2009; 37: 144-52; Kiu A, Khan S.
      Radiology of acute hip and femoral injuries. Br J Hosp Med (London) 2010; 71: M22
      M24; Zacher J, Gursche A. Regional musculoskeletal conditions: hip pain. Best
      Pract Res Clin Rheumatol 2003; 17: 71-85). A perirectal abscess as a cause of
      acute hip pain and inability to ambulate, with gluteus muscle inflammation but no
      evidence for bone or joint infection, has not been described, to the authors'
      knowledge. An 82-year-old woman with a history of diabetes, previously
      ambulatory, presented to the ED after being found on her apartment floor by a
      visiting health aide, complaining of acute pain in her left hip. Pain was
      exacerbated by palpation and range of motion testing, and she was unable to bear
      weight. There was no report of fever, rectal or abdominal pain, bleeding, or
      painful defecation. Plain films were negative for fracture or lytic lesion.
      Computerized tomography (CT) of the hip and pelvis was then obtained, which was
      negative for boney abnormality but revealed a 5-cm ischiorectal abscess with
      inflammation of the adjacent gluteus muscle. This case illustrates the
      potentially subtle nature of a deep perirectal abscess in an elderly patient. The
      CT imaging, useful for investigating the possibility of occult femoral neck
      fracture, was fortuitous in leading to the diagnosis. One must consider the
      possibility of visceral processes causing referred pain, when evaluating the
      patient with an acutely painful hip (Perron A, Miller M, Brady W. Orthopedic
      pitfalls in the ED: radiographically occult hip fracture. Am J Emerg Med 2002;
      20: 234-7; Zacher J, Gursche A. Regional musculoskeletal conditions: hip pain.
      Best Pract Res Clin Rheumatol 2003; 17: 71-85).

PMID- 20825910
TI  - Treatment of yew leaf intoxication with extracorporeal circulation.
AB  - Taxine, a yew tree toxin, is highly cardiotoxic. We report the case of a patient
      who developed severe cardiac failure and ventricular fibrillation after consuming
      yew leaves and who made a full recovery after extracorporeal life support. Yew
      poisoning can be added to the list of potential indications of extracorporeal
      life support for refractory toxic cardiogenic shock.

PMID- 20825911
TI  - The double lung point: an unusual sonographic sign of juvenile spontaneous
      pneumothorax.
AB  - Lung ultrasound is extremely useful in the bedside diagnosis of pneumothorax. The
      lung point, which is the sonographic demonstration of the point on the chest wall
      where the pleural layers adhere again, represents the limit of the pneumothorax
      extension and allows estimation of its volume. This sonographic sign is not only
      highly accurate in ruling-in pneumothorax but also helps the clinician in
      deciding whether to place a chest tube. We report a case of a young patient with
      spontaneous pneumothorax showing a double lung point. The double lung point is
      explained by the fact that the air is not free in the pleural space but forms a
      bulla surrounded by adherent pleural layers. In this case, the ultrasound
      examination could be confounding and the clinician should be aware of it. This
      phenomenon is quite rare in the juvenile spontaneous pneumothorax, being more
      frequent in case of secondary pneumothorax.

PMID- 20825912
TI  - Low-dose diltiazem in atrial fibrillation with rapid ventricular response.
AB  - OBJECTIVES: Diltiazem is one of the most commonly used medications to control the
      rapid ventricular response in atrial fibrillation (AF). The recommended starting
      dose is an intravenous bolus of 0.25 mg/kg over 2 minutes. To avoid hypotension,
      we have empirically used a lower dose of diltiazem. We compared the efficacy and
      safety of different doses of diltiazem in rapid AF. METHODS: A retrospective
      chart review was undertaken in patients who presented to the emergency department
      with rapid AF. Patients were divided into 3 groups according to diltiazem dosage:
      low dose (<= 0.2 mg/kg), standard dose (> 0.2 and <= 0.3 mg/kg), and high dose (>
      0.3 mg/kg). We compared the rates of therapeutic response (adequate rate control)
      and complications (such as hypotension). Multivariate regression analysis was
      used to determine the effect of diltiazem dose on the occurrence of
      complications. RESULTS: A total of 180 patients were included in the analysis.
      There were no significant differences in the rates of therapeutic response for
      the low-, standard-, and high-dose groups (70.5%, 77.1%, and 77.8%; P = .605).
      The rates of hypotension in the low-, standard-, and high-dose groups were 18%,
      34.9%, and 41.7%, respectively. After adjusting confounding variables, the rate
      of hypotension was significantly lower in the low-dose group in comparison with
      the standard-dose group (adjusted odds ratio, 0.39; 95% confidence interval, 0.16
      0.94). CONCLUSIONS: Low-dose diltiazem might be as effective as the standard dose
      in controlling rapid AF and reduce the risk of hypotension.

PMID- 20825913
TI  - Hypertensive heart failure: patient characteristics, treatment, and outcomes.
AB  - BACKGROUND: Acute heart failure (AHF) is a common, poorly characterized
      manifestation of hypertensive emergency. We sought to describe characteristics,
      treatment, and outcomes of patients with severe hypertension complicated by AHF.
      METHODS AND RESULTS: The observational retrospective Studying the Treatment of
      Acute hypertension (STAT) registry records data on emergency department and
      hospitalized patients receiving intravenous therapy for blood pressure (BP)
      greater than 180/110 mm Hg in 25 US hospitals. A subset of patients with HF was
      defined as pulmonary edema on chest x-ray (CXR) or an elevated B-type natriuretic
      peptide level (BNP > 500 or NTproBNP > 900 pg/mL) in patients with creatinine
      level 2.5 mg/dL or less. Remaining STAT patients, after excluding those with a
      primary neurologic diagnosis, constitute the non-HF cohort. An adverse composite
      outcome was defined as mechanical ventilation, intensive care unit (ICU)
      admission, hospital length of stay more than 1 week, or death within 30 days. Of
      1199 patients, 302 (25.2%) had AHF. Acute HF patients and non-AHF patients were
      similar in age, sex, and overall mortality, but AHF patients were more commonly
      African American, with a history of HF, diabetes or chronic obstructive pulmonary
      disease, and prior hypertension admissions. Heart failure patients had higher
      creatinine and natriuretic peptide levels but lower ejection fraction. They were
      more likely admitted to the ICU; receive electrocardiograms, bilevel positive
      airway pressure ventilation, and CXRs; and be readmitted within 90 days. Finally,
      BP decreases lower than 120 mm Hg within 12 hours were associated with an
      increased rate of the composite adverse outcome. CONCLUSIONS: Acute HF as a
      manifestation of hypertensive emergency is common, more likely in African
      Americans, and requires more clinical resources than patients with non-HF-related
      severe hypertension. Accurate BP control is critical, as declines less than 120
      mm Hg were associated with increased adverse event rates.

PMID- 20825914
TI  - Pulmonary hemorrhage resulting from roller coaster.
AB  - Roller coasters are probably one of the more popular rides at amusement parks
      around the world, and there are few reported injuries. We report a case of
      symmetric diffuse upper lobe hemorrhage resulting from roller coaster in a
      previously healthy woman. The clinical course, management, and etiology of her
      case are discussed; and the literature is reviewed. To our knowledge, pulmonary
      hemorrhage in this setting has not yet been described.

PMID- 20825915
TI  - Comparison of the Pentax AWS videolaryngoscope with the Macintosh laryngoscope in
      simulated difficult airway intubations by emergency physicians.
AB  - OBJECTIVES: The aim of this study was to evaluate the Pentax AWS
      videolaryngoscope (PAV) in intubation of simulated difficult airways by emergency
      medical staff. METHODS: Emergency medical staff and students attempted to
      intubate a manikin using 3 difficult airways settings with both the PAV and a
      Macintosh (MAC) laryngoscope in a randomized order. The success of tracheal
      intubation, time required, number of attempts, airway adjunct use, grade of view
      obtained, and participant comments were recorded. RESULTS: Significantly higher
      success rates of intubation occurred with the PAV compared with the MAC,
      irrespective of the level of training or number of previous intubations. With the
      highest difficulty setting, success occurred in 76.4% with the PAV versus 8.8%
      with the MAC. The PAV also significantly improved the Cormack and Lehane grading
      and reduced airway adjunct use, number of intubation attempts, and damage during
      intubation. CONCLUSIONS: The PAV may be a useful adjunct in difficult intubations
      by emergency medical staff.

PMID- 20825916
TI  - Emergency physician-initiated cath lab activation reduces door to balloon times
      in ST-segment elevation myocardial infarction patients.
AB  - OBJECTIVES: We evaluated the impact of emergency physician (EP)-initiated primary
      percutaneous coronary intervention (PCI) via a single-group page on door to
      balloon (D2B) interval times in patients with ST-segment elevation myocardial
      infarction. METHODS: Consecutive ST-segment elevation myocardial infarction
      patients presenting to the emergency department between February 2004 and
      September 2008 were divided into 4 groups: group 1, PCI performed on an ad hoc
      basis after cardiology consultation; group 2, primary PCI activated via a single
      group page only on-call cardiology consultation; group 3, primary PCI with EP
      cardiac catheterization laboratory (CCL) activation via the same page strategy;
      group 4, prehospital CCL activation based on prehospital diagnostic
      electrocardiogram. Composite D2B and relevant time intervals were measured for
      each time group. RESULTS: A total of 295 consecutive patients undergoing emergent
      angiography were included. Times decreased for most time intervals from groups 1
      to 4. Although there was no significant change in composite D2B or any measured
      interval time with the introduction of PCI after emergent cardiology
      consultation, each decreased significantly after implementing an EP-initiated PCI
      strategy except CCL2B (D2B 95 to 77 minutes, D2E 14 to 10 minutes, D2CCL 71 to 50
      minutes). Further significant reductions in D2B time were achieved among all
      patients after the institution of emergency medicine services activation of the
      CCL (D2B 77 to 64 minutes, D2CCL 50 to 38 minutes, CCL2B 28 to 22 minutes).
      CONCLUSIONS: A systematic process of initiating D2B recommendations, including EP
      initiated CCL activation via a single-group page, significantly reduces D2CCL and
      D2B times.

PMID- 20825917
TI  - Norepinephrine and the kidneys after cardiopulmonary resuscitation: what is the
      fuzz all about?

PMID- 20825918
TI  - Diagnostic nuclear medicine in the ED.
AB  - Although the decision to use nuclear medicine (NM) modalities in the acute care
      setting is limited by several factors, there are instances in which the use of NM
      techniques can provide elegant and efficient solutions to otherwise expensive and
      resource consuming situations. Herein, we describe the indications and NM
      techniques used for the evaluation of low-risk patients with chest pain,
      suspected pulmonary embolus, acute cholecystitis, gastrointestinal bleeding,
      acute scrotum, and the radiographically occult fracture.

PMID- 20825919
TI  - Usefulness of emergency ultrasound in nontraumatic cardiac arrest.
AB  - Treatment of nontraumatic cardiac arrest in the hospital setting depends on the
      recognition of heart rhythm and differential diagnosis of the underlying
      condition while maintaining a constant oxygenated blood flow by ventilation and
      chest compression. Diagnostic process relies only on patient's history, physical
      findings, and active electrocardiography. Ultrasound is not currently scheduled
      in the resuscitation guidelines. Nevertheless, the use of real-time
      ultrasonography during resuscitation has the potential to improve diagnostic
      accuracy and allows the physician a greater confidence in deciding aggressive
      life-saving therapeutic procedures. This article reviews the current opinions and
      literature about the use of emergency ultrasound during resuscitation of
      nontraumatic cardiac arrest. Cardiac and lung ultrasound have a great potential
      in identifying the reversible mechanical causes of pulseless electrical activity
      or asystole. Brief examination of the heart can even detect a real cardiac
      standstill regardless of electrical activity displayed on the monitor, which is a
      crucial prognostic indicator. Moreover, ultrasound can be useful to verify and
      monitor the tracheal tube placement. Limitation to the use of ultrasound is the
      need to minimize the no-flow intervals during mechanical cardiopulmonary
      resuscitation. However, real-time ultrasound can be successfully applied during
      brief pausing of chest compression and first pulse-check. Finally, lung
      sonographic examination targeted to the detection of signs of pulmonary
      congestion has the potential to allow hemodynamic noninvasive monitoring before
      and after mechanical cardiopulmonary maneuvers.

PMID- 20825920
TI  - The role of the heart-type fatty acid binding protein in the early diagnosis of
      acute coronary syndrome and its comparison with troponin I and creatine kinase-MB
      isoform.
AB  - OBJECTIVES: The aim of this study was to research the effectiveness of the heart
      type fatty acid binding protein (H-FABP) in the early diagnosis of acute coronary
      syndrome (ACS) in patients admitted to emergency service (ES) within 6 hours of
      onset of chest pain. EQUIPMENT AND METHOD: A total of 83 patients admitted with
      chest pain to our ES were included in this study. The patients were divided into
      2 groups: those with a diagnosed ACS and those diagnosed with non-cardiac-related
      chest pain. Patients were also were divided into 2 groups according to the time
      of admission: those admitted within 0 to 3 hours and 3 to 6 hours of onset of
      chest pain. Peripheral venous blood samples were obtained from all patients for H
      FABP, troponin I, and creatine kinase-MB (CK-MB) serum concentration
      measurements. RESULTS: Of a total of 83 patients, 21.6% (n = 18) were in the
      control group and 78.3% (n = 65) were in the ACS group. The average H-FABP value
      for the patients in the control group was 0.86 +/- 0.54 ng/mL. When the ACS and
      control groups were compared in means of cardiac markers for CK-MB (P = .000) and
      H-FABP (P = .000), there was a statistically significant difference, whereas no
      difference was observed for troponin I (P = .013). In the ACS group, H-FABP
      sensitivity for diagnosis was found to be 98% and specificity was 71%; CK-MB
      sensitivity was 86% and specificity was 52%; and troponin I sensitivity was 77%
      and specificity was 20%. CONCLUSIONS: For patients admitted with chest pain to
      ES, H-FABP was found to be more sensitive and specific than troponin I and CK-MB
      in the early diagnosis of ACS.

PMID- 20825921
TI  - Factors affecting stress in emergency medicine residents while working in the ED.
AB  - OBJECTIVES: The aim of this study was to identify factors other than work hours
      in the emergency department (ED) work environment contributing to resident
      stress. METHODS: This study involved a prospective cohort evaluation of emergency
      medicine residents in the ED. Twelve surveys were collected from 18 subjects, 4
      each from the day, evening, and night shifts. The Perceived Stress Questionnaire
      and a visual analog stress scale were administered. Data collected included the
      shift number of a given consecutive sequence of shifts, number of procedures
      performed, number of adverse events, average age of the patients seen by the
      resident, triage nurse-assigned acuities of the patients seen by the resident
      during the shift, the number of patients seen during a shift, the number of
      patients admitted by the resident during the shift, anticipated overtime after a
      shift, and shift-specific metrics related to overcrowding, including average
      waiting room time both for the individual residents and for all patients, average
      waiting room count for all patients, and average occupancy of the ED for all
      patients. RESULTS: Among the 216 studied shifts, there was considerable
      variability in stress both within and between residents. In the multivariate
      mixed-effect regression analysis, only anticipated overtime and process failures
      were correlated with stress. Factors related to ED overcrowding had no
      significant effect on resident stress. CONCLUSIONS: Resident stress was most
      impacted by anticipation of overtime and adverse events. Overcrowding in the ED
      and traditional measures of workload did not seem to affect stress as much.

PMID- 20825922
TI  - Management of patients with acute atrial fibrillation in the ED.
AB  - BACKGROUND: Patients with acute atrial fibrillation with a history of mild
      structural heart disease could be considered for rhythm conversion. METHODS:
      Patients received intravenous flecainide, propafenone, or amiodarone on
      presentation and a second dose after 6 hours if atrial fibrillation persisted. No
      randomization was used, and drugs were given at the discretion of the treating
      physician. Primary end point was rhythm conversion within the first 6 hours from
      presentation. Secondary end points included rhythm conversion, time to rhythm
      conversion, and adverse drug effects within 24 hours. RESULTS: Among the 378
      patients enrolled, 37 (10%) recovered sinus rhythm before therapy was given. Of
      the remaining 341 patients, 43 (13%) received flecainide, 187 (55%) received
      propafenone, and 111 (32%) received amiodarone. Baseline clinical characteristics
      were homogeneous among groups. Rhythm conversion was obtained in 87% of treated
      patients overall. Within 6 hours, the primary end point was achieved in a higher
      proportion in the flecainide and propafenone groups (72% and 55%, respectively)
      as compared with the amiodarone group (30%; P < .001). The mean time to the end
      point overall was shorter in the flecainide and propafenone groups (178 +/- 227
      and 292 +/- 285 minutes, respectively) as compared with the amiodarone group (472
      +/- 269 minutes; P < .001). Length of in-hospital stay in the amiodarone group
      was significantly higher (26.1 +/- 22.4 hours) compared with the flecainide and
      propafenone groups (8.9 +/- 10.3 and 11.0 +/- 13.8 hours; respectively; P =
      .001). No significant differences were found in adverse drug effects.
      CONCLUSIONS: Flecainide and propafenone achieve rhythm control in a higher
      proportion of patients as compared with amiodarone within a 6-hour management.

PMID- 20825923
TI  - Emergency medical services' use of poison control centers for unintentional drug
      ingestions.
AB  - INTRODUCTION: Every year, emergency medical services (EMS) providers respond to
      thousands of calls for toxic ingestions. Many systems have begun using poison
      control centers (PCCs) when unsure of disposition. We sought to determine the
      type of exposures EMS personnel were using the PCCs for and treatments suggested.
      Secondary end points included transport rate after consulting the PCC and amount
      of money saved by avoiding unnecessary transports. METHODS: This study was a
      qualitative retrospective chart review. Encounters between 2004 and 2006
      originating in Austin, TX, were queried and limited to accidental ingestion calls
      placed by prehospital personnel. Data from charts were then analyzed. RESULTS: A
      total of 386 charts met inclusion criteria for this study. Household chemicals
      were the most frequently encountered agents. The most common recommendation was
      to observe patients at home for the development of concerning symptoms. In only
      6% of cases did the PCC recommend administration of medication. Also of interest
      was the fact that only 63 patients were transported (16%). CONCLUSIONS: It is
      unreasonable to expect prehospital providers to know what to do for every toxic
      exposure. This study suggests that the use of PCCs by EMS systems can be
      beneficial to patient care. For the time period of this study, EMS crews who
      contacted the PCC saved the City of Austin more than $205,000 in unnecessary
      ambulance transport costs. When emergency department expenses are factored in and
      other regions of the country are included, the savings would likely be much
      greater. This modality is an important resource for providers in a potentially
      uncertain realm.

PMID- 20825924
TI  - Ultrasound-guided pigtail catheters for drainage of various pleural diseases.
AB  - OBJECTIVE: Little is known about the efficacy and safety of ultrasound-guided
      pigtail catheters for the management of various pleural diseases in the emergency
      department, ward, and intensive care unit. METHODS: We conducted a retrospective
      study in a university hospital during a 1-year interval. RESULTS: A total of 276
      patients (178 men and 98 women) underwent 332 pigtail catheters (the drain size
      ranged from 10F to 16F) under ultrasound guidance. The mean +/- SEM patient age
      was 59 +/- 18 years, and mean duration of drainage was 6.1 +/- 2 days. A total of
      64 drains (19.2%) were inserted for pneumothoraces; 98 drains (29.5%), for
      malignant effusions; 119 drains (35.8%), for parapneumonic effusions/empyemas;
      and 38 drains (11.4%), for massive transudate pleural effusions. The overall
      success rate was 72.9%. The success rate was highest when the drain was used to
      treat massive transudate effusions (81.6%) and malignant pleural effusions
      (75.5%), followed by parapneumonic effusions/empyemas (72.2%), hemothoraces
      (66.6%), and pneumothoraces (64.0%). Only 10 (3.0%) drains had complications due
      to the procedure, including infection (n = 4, 1.2%), dislodgment (n = 4, 1.2%),
      wound bleeding at the pigtail catheter puncture area complicated with
      hemothoraces (n = 1, 0.3%), and lung puncture (n = 1, 0.3%). There was no
      significant difference in success rate when different catheter sizes were used to
      treat pleural diseases. CONCLUSIONS: Ultrasound-guided pigtail catheters provide
      a safe and effective method of draining various pleural diseases. We strongly
      suggest that ultrasound-guided pigtail catheters be considered as the initial
      draining method for a variety of pleural diseases.

PMID- 20825925
TI  - Does sex influence the allocation of life support level by dispatchers in acute
      chest pain?
AB  - AIM: The aim of this study was to evaluate (a) the differences between men and
      women in symptom profile, allocated life support level (LSL), and presence of
      acute myocardial infarction (AMI), life-threatening condition (LTC), or death and
      (b) whether a computer-based decision support system could improve the allocation
      of LSL. PATIENTS: All patients in Goteborg, Sweden, who called the dispatch
      center because of chest pain during 3 months (n = 503) were included in this
      study. METHODS: Age, sex, and symptom profile were background variables. Based on
      these, we studied allocation of LSL by the dispatchers and its relationship to
      AMI, LTC, and death. All evaluations were made from a sex perspective. Finally,
      we studied the potential benefit of using a statistical model for allocating LSL.
      RESULTS: The advanced life support level (ALSL) was used equally frequently for
      men and women. There was no difference in age or symptom profile between men and
      women in relation to allocation. However, the allocation of ALSL was predictive
      of AMI and LTC only in men. The sensitivity was far lower for women than for men.
      When a statistical model was used for allocation, the ALSL was predictive for
      both men and women. Using a separate model for men and women respectively,
      sensitivity increased, especially for women, and specificity was kept at the same
      level. CONCLUSION: This exploratory study indicates that women would benefit most
      from the allocation of LSL using a statistical model and computer-based decision
      support among patients who call for an ambulance because of acute chest pain.
      This needs further evaluation.

PMID- 20825926
TI  - Domicile-related carbon monoxide poisoning in cold months and its relation with
      climatic factors.
AB  - BACKGROUND: Many studies have identified strong correlations between winter
      months and acute, unintentional carbon monoxide (CO) poisoning. In this study, we
      aimed to investigate the incidence pattern of acute domicile-related CO poisoning
      in Beijing and its relation with climatic factors. METHODS: Data on CO poisoning
      were collected from the emergency medical service system during August 1, 2005,
      to July 31, 2007, in Beijing. Variations of the monthly and seasonal distribution
      of CO poisoning occurrences were examined with chi(2) testing. Climatic data
      including temperature, barometric pressure, humidity, wind speed, and visibility
      were obtained from the Beijing Meteorological Bureau. Correlations between the
      occurrence of CO poisoning and mean of each meteorological parameter spanning 3
      days were analyzed with partial correlation test, with related parameters
      controlled. RESULTS: Significant differences were found among the cases occurring
      each month of the year (P < .001). The monthly caseload reached the peak and the
      nadir in January and in September, respectively. During the cold period, 3331
      patients were recorded, accounting for 88.4% of the total cases of the 2-year
      study period. Among the 5 climatic parameters, only temperature had a significant
      inverse correlation with the occurrence of CO poisoning (P < .001, r = -0.467).
      CONCLUSIONS: The incidences of CO poisoning were highest during winter,
      particularly during the time period when charcoal or coal use for indoor heating
      would be most prevalent in Beijing.

PMID- 20825927
TI  - Determining the accuracy of base deficit in diagnosis of intra-abdominal injury
      in patients with blunt abdominal trauma.
AB  - BACKGROUND: Blunt abdominal trauma is a leading cause of morbidity and mortality
      among all age groups. A multiplicity of diagnostic modalities exists to evaluate
      the abdomen. We sought to assess the diagnostic performance of base deficit (BD)
      in identifying intra-abdominal injury in patients with blunt abdominal trauma.
      METHODS: A prospective, nonrandomized series of patients with blunt abdominal
      trauma admitted into the 2 emergency departments was investigated from September
      2007 to September 2008. Arterial blood samples were analyzed. According to BD,
      the patients were divided into 2 groups: group 1 who had a BD of -6 or lower and
      group 2 who had a BD more than -6. Ultrasonography, computed tomographic scan, or
      laparotomy was performed to find intra-abdominal injury. Follow-up at 7 days by
      telephone interview was obtained on patients who were discharged. RESULTS: A
      total of 400 patients were enrolled, with a mean (SD) age of 34.8 +/- 17.1 years.
      Two hundred sixty-eight (67%) of them were male. Seventy-six (19%) of patients
      had a BD of -6 or lower. Sixty-eight (17%) of them showed to have intra-abdominal
      injury with a BD of approximately -8.7 +/- 3.2, compared with patients without
      intra-abdominal injury, -0.4 +/- 0.1. Patients with a BD of -6 or lower achieved
      more laparotomy and blood transfusion compared with patients with a BD more than 
      6. On receiver operating characteristic curve analysis, the cutoff point of -6
      was obtained with sensitivity and specificity of 88.2% and 95.2% and with
      positive and negative predictive values of 79% and 97.5%, respectively. None of
      outpatients had abdominal problem in telephone follow-up. CONCLUSIONS: These data
      show that the BD is an early available important indicator to identify intra
      abdominal injury in patients with blunt abdominal trauma, as well as a high
      transfusion requirement.

PMID- 20825928
TI  - Cardiac ultrasound helps for differentiating the causes of acute dyspnea with
      available B-type natriuretic peptide tests.
AB  - INTRODUCTION: The aim of this study was to evaluate the role of cardiac
      ultrasound in diagnosing acute heart failure (AHF) in patients with acute dyspnea
      with available plasma B-type natriuretic peptide (BNP) level. METHODS: Patients
      with acute dyspnea presenting to the emergency department (ED) of a tertiary
      medical center were prospectively enrolled. The enrolled 84 patients received
      both BNP tests and cardiac ultrasound studies and were classified into AHF and
      non-heart failure groups. RESULTS: Plasma BNP levels were higher in the AHF group
      (1236 +/- 1123 vs 354 +/- 410 pg/mL; P < .001). The AHF group had larger left
      ventricular end-diastolic dimension (LVEDD; 32 +/- 7 vs 27 +/- 4 mm/m(2); P <
      .001) and worse left ventricular ejection fraction (52% +/- 18% vs 64% +/- 15%; P
      = .003). Multiple logistic regression analysis showed that both BNP levels more
      than 100 pg/mL and LVEDD were independent predictors for AHF. In patients with
      plasma BNP levels within gray zone of 100 to 500 pg/mL, LVEDD was larger in the
      AHF group than that in the non-heart failure group (29 +/- 4 vs 26 +/- 4 mm/m(2);
      P = .044). CONCLUSION: Both LVEDD by cardiac ultrasound and BNP levels can help
      emergency physicians independently diagnose AHF in the ED. In patients with
      plasma BNP levels within 100 to 500 pg/mL, cardiac ultrasound can help
      differentiate heart failure or not.

PMID- 20825929
TI  - Assessing the prevalence of modifiable risk factors in older patients visiting an
      ED due to a fall using the CAREFALL Triage Instrument.
AB  - OBJECTIVE: Falls in older people are a common presenting complaint. Knowledge of
      modifiable risk factors may lead to a more tailored approach to prevent recurrent
      falls and/or fractures. We investigated prevalence of 8 modifiable risk factors
      for recurrent falling and/or a serious consequence of the fall among older
      patients visiting the emergency department after a fall with the Combined
      Amsterdam and Rotterdam Evaluation of Falls Triage Instrument (CTI), a self
      administrated questionnaire that consists of questions concerning demographics,
      possible cause(s) of the fall, and questions relating to (modifiable) risk
      factors for falling. METHODS: After treatment for their injuries, 1077
      consecutive patients 65 years or older visiting the accident and emergency
      department due to a fall were evaluated by the CTI. The following were assessed:
      impaired vision, mobility disorder, fear of falling, mood disorder, high risk of
      osteoporosis, orthostatic hypotension, incontinence, and polypharmacy. RESULTS:
      The percentage of respondents who returned the questionnaire was 59.3%. The mean
      (SD) age was 78.5 (7.5) years, and 57.8% experienced a fall with serious
      consequences. There were 60.9% of patients with a recurrent fall versus 51% with
      a first fall who experienced with a serious consequence (P = .025). Age and risk
      factors mobility disorder (odds ratio [OR], 1.9; 95% confidence interval [CI],
      1.1-3.3), high risk of osteoporosis (OR, 2.0; 95% CI, 1.2-3.2), incontinence (OR,
      1.7; 95% CI, 1.0-2.7), fear of falling (OR, 2.2; 95% CI, 1.3-3.7), and
      orthostatic hypotension (OR, 2.4; 95% CI, 1.4-4.2) were independently associated
      with a recurrent fall. Age and high risk of osteoporosis were the only risk
      factors predicting a serious consequence of a fall (OR, 4.6; 95% CI, 2.9-7.2).
      CONCLUSIONS: Age and 5 modifiable risk factors assessed with the CTI were
      independently associated with a recurrent fall. Only high risk of osteoporosis
      was associated with a serious consequence.

PMID- 20825930
TI  - Ultrasound-guided reduction of distal radius fractures.
AB  - INTRODUCTION: In our local emergency departments (EDs), manipulation and
      reduction (M&R) of distal radius fractures are performed by emergency doctors,
      with blind manual palpation, using postreduction x-rays to assess adequacy. We
      sought to study the effectiveness of ultrasound guidance in the reduction of
      distal radius fractures in adult patients presenting to a regional ED. METHODS:
      This was a before-and-after study. Eligible patients were adults older than 21
      years who presented to the ED with distal radius fractures that required M&R.
      Sixty-two patients were prospectively enrolled from October 2007 until June 2008,
      and they underwent ultrasound-guided M&R. The control group was a retrospective
      cohort of 102 patients who presented from January to June 2007. They had M&R done
      using the blind manual palpation method. All M&R procedures were performed by
      doctors within the ED, and supervision was provided by senior emergency
      physicians. Ultrasound guidance was performed by the senior emergency physicians.
      RESULTS: Baseline characteristics between the ultrasound and control groups were
      similar. The rate of repeat M&R was reduced in the ultrasound group (1.6% vs
      8.8%; P = .056). The postreduction radiographic indices were similar between the
      2 groups, although the ultrasound group had improved volar tilt (mean, 5.93
      degrees  vs 2.61 degrees ; P = .048). An incidental finding of a reduced
      operative rate was also found between the ultrasound and control groups (4.9% vs
      16.7%; P = .02). CONCLUSION: Ultrasound guidance is effective and recommended for
      routine use in the reduction of distal radius fractures.

PMID- 20825931
TI  - Diagnosing pediatric appendicitis: usefulness of laboratory markers.
AB  - OBJECTIVE: This study aimed to evaluate the utility of C-reactive protein (CRP),
      procalcitonin (PCT), D-lactate, and white blood cell (WBC) count as an aid to
      distinguish appendicitis from other diagnoses. METHODS: This prospective,
      observational study was conducted at an urban tertiary academic pediatric
      emergency department (ED). Subjects aged 1 to 18 years presenting with abdominal
      pain suspicious for acute appendicitis were enrolled. Data included history,
      physical examination, laboratory data (complete blood count, CRP, D-lactate, PCT
      [semiquantitative]), laboratory results, x-rays, surgical consultation notes,
      histopathology, and admission data. Stepwise logistic regression analysis was
      performed to identify independent risk factors. RESULTS: Two hundred nine
      subjects (59% male, 41% female) were enrolled over 6 months. One hundred fifteen
      subjects were histologically diagnosed with appendicitis; 94 subjects did not
      have appendicitis and were used as controls. Mean values of WBC, CRP, PCT, and
      absolute neutrophil count in subjects with definitive appendicitis were
      significantly higher than in subjects with no definitive appendicitis. D-Lactate
      levels were noncorrelative. Significant independent risk factors identified for
      definitive appendicitis included WBC count more than 12 cells * 1000/mm(3)
      (adjusted odds ratio [AOR], 6.54), CRP level greater than 3 mg/dL (AOR, 3.44),
      presence of hopping pain (AOR, 2.69), and presence of pain with walking (AOR,
      2.56). Odds ratio for definitive appendicitis and its 95% confidence interval was
      found to be 7.75 for subjects with both WBC more than 12 cells * 1000/mm(3) and
      CRP greater than 3 mg/dL. CONCLUSIONS: C-reactive protein with WBC is useful in
      distinguishing appendicitis from other diagnoses in pediatric subjects presenting
      to the ED. White blood cell count greater than >12 cells * 1000/mm(3) and CRP
      greater than 3 mg/dL increases the likelihood of appendicitis. D-Lactate is not a
      useful laboratory adjunct.

PMID- 20825932
TI  - Effects of compression-to-ventilation ratio on compression force and rescuer
      fatigue during cardiopulmonary resuscitation.
AB  - INTRODUCTION: Although increasing consecutive compressions during cardiopulmonary
      resuscitation (CPR) is beneficial to patients, it possibly affects the workload
      and, ultimately, the quality of CPR. This study examines the effects of
      compression-to-ventilation ratio on external chest compression performance of
      rescuers. METHODS: Subjects were 17 health care providers. Each participant
      performed CPR with 3 compression-to-ventilation ratios: 15:2, 30:2, and 50:5. The
      duration of CPR was 5 minutes in each group, with a rest period of 50 minutes in
      between. The manikin was equipped with a 6-axis force load cell to measure the
      force applied. An 8-camera digital motion analysis system was used to collect the
      3-dimensional trajectory information. Data were compared using the crossover
      design. Ratings of perceived exertion and body area discomfort were measured.
      RESULTS: The mean compression forces (in Newtons) delivered at 1 minute 20
      seconds to 1 minute 40 seconds and at 4 minutes 20 seconds to 4 minutes 40
      seconds were 494.65 +/- 53.58 and 478.64 +/- 50.29, respectively (P = .047), for
      compression-to-ventilation ratios of 15:2; 473.57 +/- 49.69 and 435.59 +/- 56.79,
      respectively (P < .001), for ratios of 30:2; and 468.44 +/- 38.05 and 442.18 +/-
      43.40, respectively (P = .012), for ratio of 50:5. Diminished compression force
      in the ratio 50:5 was observed at 1 minute 20 seconds, and in the 30:2 ratio, it
      was observed at 4 minutes 20 seconds. The mean joint angles in each group did not
      differ significantly between 1 minute 20 seconds and 4 minutes 20 seconds. The
      Ratings of Perceived Exertion Scale was 3.38 +/- 1.64 in 15:2, 4.06 +/- 1.43 in
      30:2, and 4.35 +/- 1.54 in 50:5 (P = .045). Waist discomfort was noted in 50:5
      after 4 minutes 20 seconds of external chest compression. CONCLUSIONS: Rescuer
      fatigue must be considered when raising the consecutive compression during CPR.
      Switching the compressor every 2 minutes should be followed where possible.

PMID- 20825933
TI  - Combination of white blood cell count with liver enzymes in the diagnosis of
      blunt liver laceration.
AB  - BACKGROUND: It is sometimes difficult to decide whether to perform abdominal
      computed tomographic (CT) scans for possible liver laceration in patients who
      have sustained less severe or minor blunt abdominal trauma. This study was
      conducted to find out whether the basic laboratory workup could provide
      information of possible liver laceration in blunt abdominal trauma patients and
      act as an indication for CT scans. METHODS: In this retrospective case-control
      study, we included 289 patients who had sustained blunt abdominal injury for
      which they received abdominal CT scans in our emergency department. Of the 289
      patients, the study group (n = 42) included patients who had been found to have
      liver lacerations after obtaining the CT; the controls (n = 42) were those not
      found to have such injuries by the same method with matching of age and sex.
      RESULTS: In patients with blunt abdominal injuries, there is a strong difference
      in liver laceration between elevation of white blood cell (WBC) counts (P =
      .001), aspartate aminotransferase (AST) (P < .001), and alanine aminotransferase
      (ALT) (P < .001). A logistic regression model demonstrated that WBC count and AST
      were independently associated with liver laceration. With elevations of serum AST
      greater than 100 IU/L, ALT greater than 80 IU/L, and WBC count greater than 10
      000/mm(3), we found a sensitivity and specificity of 90.0% and 92.3%,
      respectively, in the 42 liver laceration victims. CONCLUSION: In patients with
      blunt abdominal trauma, elevated WBC counts together with elevated AST and ALT
      are strongly associated with liver laceration and warrant further imaging studies
      and management.

PMID- 20825934
TI  - Radiation exposure in emergency physicians working in an urban ED: a prospective
      cohort study.
AB  - OBJECTIVE: The National Council on Radiation Protection (NCRP) limits health care
      associated occupational exposures to radiation to 5000 mrem/y. Previous studies
      suggested that emergency physicians were not exposed over this limit. Their
      relevance to contemporary practice is unknown. We hypothesized that emergency
      physicians are currently exposed to radiation levels above the NCRP limits.
      METHODS: This prospective cohort study was conducted at an urban, academic, level
      I trauma center emergency department (ED). Thermoluminescent dosimeter radiation
      badges were placed on the torso and ring finger of all physicians staffing the ED
      during May 2008. Thermoluminescent dosimeter badges were affixed to 8 portable
      phones that are carried by physicians in the ED 24 hours a day. At the end of the
      study period, exposure dose for each subject was estimated. RESULTS: Seventy-five
      physicians enrolled in the study; 41 residents worked a median of 94 hours and 34
      attendings worked a median of 54 hours. Compliance for physician badge wearing
      was 99%, ring wearing was 98%, and phone wearing was 100%. Two subjects had
      detectable levels of radiation on their torso thermoluminescent dosimeters of 4
      and 1 mrem, respectively. One phone badge had a detectable level of 1 mrem. The
      annual extrapolated exposure for the subject with the highest radiation level
      would have been 50 mrem, below the 5000 mrem exposure limit for health care
      workers. CONCLUSION: Emergency physicians working in an urban, academic, level I
      trauma center ED do not appear to be at risk of exceeding the NCRP dose limits
      for ionizing radiation exposure to their torso or extremities.

PMID- 20825935
TI  - [Diagnostic efficacy and discriminatory capacity of positron emission tomography
      combined with axial tomography of adrenal lesions].
AB  - INTRODUCTION: The usefulness of 18fluorodeoxyglucose positron emission tomography
      combined with axial tomography (PET-CT) in diagnosing whether adrenal tumours are
      benign or malignant is assessed. MATERIAL AND METHODS: A retrospective study
      conducted between June 2005 and May 2009 on a consecutive series of patients on
      whom a PET-CT scan was performed to study suspected malignant adrenal disease.
      Focal uptakes were assessed, along with the maximum standard uptake value (SUV),
      and the ratio of the maximum adrenal/hepatic value. The sensitivity, specificity,
      positive and negative predictive value of the test, the maximum adrenal uptake
      values and the ratio for those where the diagnostic yield was maximum. RESULTS:
      Fifteen patients were included. The final diagnosis showed malignancy in eight
      and seven were benign. Ten patients had adrenal uptake: three in benign lesions
      and seven in neoplasias, with a mean uptake value of 6.3 (3.2 in benign lesions
      and 9.0 in malignant lesions). The mean adrenal/hepatic ratio was 1.8 (0.9 in
      benign and 2.6 in malignant lesions). When the presence of adrenal uptake is
      associated with a final diagnosis of malignancy, we obtained a sensitivity of
      87.5%, a specificity of 57.1%, and a positive and negative predictive value of
      70% and 80%, respectively. An SUV cut-off value of 6, or an adrenal/hepatic
      uptake ratio of 2, gave a sensitivity of 75%, a specificity of 100%, and a
      positive and negative predictive value of 100% and 77.7%, respectively.
      CONCLUSIONS: PET-CT has a high ability to discriminate between benign and
      malignant lesions in the adrenal disease studied.

PMID- 20825936
TI  - Know thyself: metacognitive networks and measures of consciousness.
AB  - Subjective measures of awareness rest on the assumption that conscious knowledge
      is knowledge that participants know they possess. Post-Decision Wagering (PDW),
      recently proposed as a new measure of awareness, requires participants to place a
      high or a low wager on their decisions. Whereas advantageous wagering indicates
      awareness of the knowledge on which the decisions are based, cases in which
      participants fail to optimize their wagers suggest performance without awareness.
      Here, we hypothesize that wagering and other subjective measures of awareness
      reflect metacognitive capacities subtended by self-developed metarepresentations
      that inform an agent about its own internal states. To support this idea, we
      present three simulations in which neural networks learn to wager on their own
      responses. The simulations illustrate essential properties that are required for
      such metarepresentations to influence PDW as a measure of awareness. Results
      demonstrate a good fit to human data. We discuss the implications of this
      modeling work for our understanding of consciousness and its measures.

PMID- 20825937
TI  - Response to: Harris and Jim (2010) commentary on Delistraty et al. (2010) .

PMID- 20825938
TI  - [High risk syncope referred from the Emergency Service: Do we forget the exercise
      stress test?].

PMID- 20825939
TI  - [Short history told without nostalgia and still open to the future].

PMID- 20825940
TI  - Hydro-mechanical coupling in the periodontal ligament: a porohyperelastic finite
      element model.
AB  - Harmonic tension-compression tests at 0.1, 0.5 and 1 Hz on hydrated bovine
      periodontal ligament (PDL) were numerically simulated. The process was modeled by
      finite elements (FE) within the framework of poromechanics, with the objective of
      isolating the contributions of the solid- and fluid phases. The solid matrix was
      modeled as a porous hyperelastic material (hyperfoam) through which the
      incompressible fluid filling the pores flowed in accordance with the Darcy's law.
      The hydro-mechanical coupling between the porous solid matrix and the fluid phase
      circulating through it provided an apparent time-dependent response to the PDL,
      whose rate of deformation depended on the permeability of the porous solid with
      respect to the interstitial fluid. Since the PDL was subjected to significant
      deformations, finite strains were taken into account and an exponential
      dependence of PDL permeability on void ratio - and therefore on the deformation
      state - was assumed. PDL constitutive parameters were identified by fitting the
      simulated response to the experimental data for the tests at 1 Hz. The values
      thus obtained were then used to simulate the tests at 0.1 and 0.5 Hz. The results
      of the present simulation demonstrate that a porohyperelastic model with variable
      permeability is able to describe the two main aspects of the PDL's response: (1)
      the dependency on strain-rate-the saturated material can develop volumetric
      strains by only exchanging fluid and (2) the asymmetry between tension and
      compression, which is due to the effect of both the permeability and the elastic
      properties on deformation.

PMID- 20825941
TI  - Combined probabilistic and principal component analysis approach for multivariate
      sensitivity evaluation and application to implanted patellofemoral mechanics.
AB  - Many aspects of biomechanics are variable in nature, including patient geometry,
      joint mechanics, implant alignment and clinical outcomes. Probabilistic methods
      have been applied in computational models to predict distributions of performance
      given uncertain or variable parameters. Sensitivity analysis is commonly used in
      conjunction with probabilistic methods to identify the parameters that most
      significantly affect the performance outcome; however, it does not consider
      coupled relationships for multiple output measures. Principal component analysis
      (PCA) has been applied to characterize common modes of variation in shape and
      kinematics. In this study, a novel, combined probabilistic and PCA approach was
      developed to characterize relationships between multiple input parameters and
      output measures. To demonstrate the benefits of the approach, it was applied to
      implanted patellofemoral (PF) mechanics to characterize relationships between
      femoral and patellar component alignment and loading and the resulting joint
      mechanics. Prior studies assessing PF sensitivity have performed individual
      perturbation of alignment parameters. However, the probabilistic and PCA approach
      enabled a more holistic evaluation of sensitivity, including identification of
      combinations of alignment parameters that most significantly contributed to
      kinematic and contact mechanics outcomes throughout the flexion cycle, and the
      predictive capability to estimate joint mechanics based on alignment conditions
      without requiring additional analysis. The approach showed comparable results for
      Monte Carlo sampling with 500 trials and the more efficient Latin Hypercube
      sampling with 50 trials. The probabilistic and PCA approach has broad
      applicability to biomechanical analysis and can provide insight into the
      interdependencies between implant design, alignment and the resulting mechanics.

PMID- 20825942
TI  - Evaluation of extensional and torsional stiffness of single actin filaments by
      molecular dynamics analysis.
AB  - It is essential to investigate the mechanical behaviour of cytoskeletal actin
      filaments in order to understand their critical role as mechanical components in
      various cellular functional activities. These actin filaments consisting of
      monomeric molecules function in the thermal fluctuations. Hence, it is important
      to understand their mechanical behaviour on the microscopic scale by comparing
      the stiffness based on thermal fluctuations with the one experimentally measured
      on the macroscopic scale. In this study, we perform a large-scale molecular
      dynamics (MD) simulation for a half-turn structure of an actin filament. We
      analyse its longitudinal and twisting Brownian motions in equilibrium and
      evaluated its apparent extensional and torsional stiffness on the nanosecond
      scale. Upon increasing the sampling-window durations for analysis, the apparent
      stiffness gradually decreases and exhibits a trend to converge to a value that is
      close to the experimental value. This suggests that by extrapolating the data
      obtained in the MD analysis, we can estimate the experimentally determined
      stiffness on the microsecond to millisecond scales. For shorter temporal scales,
      the apparent stiffness is larger than experimental values, indicating that fast,
      local motions of the molecular structure are dominant. To quantify the local
      structural changes within the filament on the nanosecond scale and investigate
      the molecular mechanisms, such as the binding of the actin-regulatory proteins to
      the filaments, it is preferable to analyse the mechanical behaviour on the
      nanometre and nanosecond scales using MD simulation.

PMID- 20825943
TI  - Numerical simulation of the failure of ventricular tissue due to deep
      penetration: the impact of constitutive properties.
AB  - Lead perforation is a rare but serious clinical complication of pacemaker
      implantation, and towards understanding this malfunction, the present study
      investigated myocardial failure due to deep penetration by an advancing rigid
      punch. To this end, a non-linear Finite Element model was developed that
      integrates constitutive data published in the literature with information from in
      vitro tensile testing in cross-fibre direction of porcine myocardial tissue. The
      Finite Element model considered non-linear, isotropic and visco-elastic
      properties of the myocardium, and tissue failure was phenomenologically described
      by a Traction Separation Law. In vitro penetration testing of porcine myocardium
      was used to validate the Finite Element model, and a particular objective of the
      study was to investigate the impact of different constitutive parameters on the
      simulated results. Specifically, results demonstrated that visco-elastic
      properties of the tissue strongly determine the failure process, whereas
      dissipative effects directly related to failure had a minor impact on the
      simulation results. In addition, non-linearity of the bulk material did not
      change the predicted peak penetration force and the simulations did not reveal
      elastic crack-tip blunting. The performed study provided novel insights into
      ventricular failure due to deep penetration, and provided useful information with
      which to develop numerical failure models.

PMID- 20825944
TI  - Measured and estimated ground reaction forces for multi-segment foot models.
AB  - Accurate measurement of ground reaction forces under discrete areas of the foot
      is important in the development of more advanced foot models, which can improve
      our understanding of foot and ankle function. To overcome current equipment
      limitations, a few investigators have proposed combining a pressure mat with a
      single force platform and using a proportionality assumption to estimate subarea
      shear forces and free moments. In this study, two adjacent force platforms were
      used to evaluate the accuracy of the proportionality assumption on a three
      segment foot model during normal gait. Seventeen right feet were tested using a
      targeted walking approach, isolating two separate joints: transverse tarsal and
      metatarsophalangeal. Root mean square (RMS) errors in shear forces up to 6% body
      weight (BW) were found using the proportionality assumption, with the highest
      errors (peak absolute errors up to 12% BW) occurring between the forefoot and
      toes in terminal stance. The hallux exerted a small braking force in opposition
      to the propulsive force of the forefoot, which was unaccounted for by the
      proportionality assumption. While the assumption may be suitable for specific
      applications (e.g. gait analysis models), it is important to understand that some
      information on foot function can be lost. The results help highlight possible
      limitations of the assumption. Measured ensemble average subarea shear forces
      during normal gait are also presented for the first time.

PMID- 20825945
TI  - Mechanics of cranial sutures using the finite element method.
AB  - To investigate how cranial suture morphology and the arrangement of sutural
      collagen fibres respond to compressive and tensile loads, an idealised bone
      suture-bone complex was analysed using a two-dimensional finite element model.
      Three suture morphologies were simulated with an increasing interdigitation index
      (I.I.): butt-ended, moderate interdigitated, and complex interdigitated. The
      collagen matrix within all sutures was modelled as an isotropic material, and as
      an orthotropic material in the interdigitated sutures with fibre alignment as
      reported in studies of miniature pigs. Static uniform compressive or tensile
      loading was applied to the complex. In interdigitated sutures with isotropic
      material properties, the orientation of the maximum (tensile) principal stresses
      within the suture matched the collagen fibre orientation observed in compressed
      and tensed sutures of miniature pigs. This suggests that randomly arranged
      sutural collagen fibres could optimise to an orientation most appropriate to
      withstand the predominant type of loading. A compression-resistant fibre
      arrangement imparted the highest suture strain energy relative to the isotropic
      and tension-resistant arrangements, indicating that this configuration maximises
      energy storage. A comparison across the different suture morphologies indicated
      that bone strain energy generally decreased with a decrease in I.I., irrespective
      of the sutural fibre arrangement. However, high bone stress at the
      interdigitation apices shifted to the limbs of the suture with an increase in
      I.I. These combined findings highlight the importance of suture morphology and
      anisotropy as properties having a significant influence on sutural mechanics.

PMID- 20825946
TI  - A computational human model for exploring the role of the feet in balance.
AB  - Many studies concerning human balance use computational models that represent the
      body as a single, double, or triple inverted pendulum while ignoring the feet.
      Clinical research, however, has begun to more closely examine specific
      contributions of the feet in balance, leading to a disparity between the state of
      clinical research and the models used for simulation. Here, we expand the single
      inverted pendulum model by adding four additional rigid links to represent the
      feet. Model parameters, equations of motion, actuation based on human
      musculature, and control based on proprioception are discussed. Computation of
      ground reaction forces under the heel, forefoot, and toes is also addressed.
      Simulations focusing on the role of the toes and toe muscles in static balance
      and forward leaning are presented.

PMID- 20825947
TI  - The influence of nanoparticle shape on the drying of colloidal suspensions.
AB  - Dried deposits of spherical Ludox silica and disk-like laponite clay
      nanoparticles have been examined by dark-field optical microscopy and atomic
      force microscopy (AFM) to investigate the effects of nanoparticle shape on the
      deposit structure. Dark-field optical images indicated that a higher
      concentration of Ludox nanoparticles was required, compared to laponite, for an
      optically visible deposit to be formed. Compared with the relatively simple ring
      like features observed at the edges of Ludox deposits, the laponite deposits were
      more complex, with dendritic features appearing below 10ppm that disappeared at
      higher laponite concentrations. AFM images revealed that whilst the Ludox rim
      deposit structure gradually increased in height and width with increasing
      nanoparticle concentration, the laponite rim deposits increased steadily in
      height up to 1ppm, above which the rim height suddenly decreased and the deposit
      structure became smoother. The widths of the rim deposits were observed to
      increase in a similar manner for both nanoparticle types. Nanoparticle shape is
      suggested as the main reason for differences in the structural features of the
      rim for each nanoparticle type. The disk-like laponite forms tall thin rim
      profiles at low concentrations, before creating a more uniform rim profile at
      higher concentrations. We suggest that a critical laponite rim height is reached
      before partial collapse of the nanoparticle stack at the rim takes place as the
      particle concentration is further increased. This produces much thinner and
      smoother films of laponite at high particle concentrations than is found for
      similar concentrations of Ludox. Our work suggests that both the shape and the
      concentration of the nanoparticles themselves are crucial in determining the
      structure of the final dried nanoparticle deposit.

PMID- 20825948
TI  - Differentiating and characterizing geminal silanols in silicas by (29)Si NMR
      spectroscopy.
AB  - Single and geminal hydroxyl species in silicas have been characterized using
      solid-state (29)Si NMR spectroscopy. Differentiating hydroxyl types is important
      in understanding their roles in chemical toxicity mechanisms for inhaled
      crystalline silicas responsible for silicosis. (1)H-(29)Si cross polarization NMR
      spectroscopy has been employed to obtain (29)Si NMR chemical shift data and
      signal accrual and relaxation characteristics. Spectral deconvolution is used to
      examine relative single and geminal hydroxyl resonance areas for a series of
      representative silicas and silica gels. Silicon-containing materials examined
      include 1878a quartz, and 1879a cristobalite from the National Institute for
      Science and Technology, kaolin, and several widely used respirable silicas and
      silica gels. Geminal hydroxyls were observed in every case, with relative
      resonance areas accounting for 21-65% of total hydroxyl signals. Factors
      affecting relative areas measured as a function of contact time, relaxation, and
      surface area are discussed. Subsequent (29)Si and (31)P NMR studies of a silica
      coated with various sodium hydrogen phosphates show preferential single silanol
      phosphate interaction for basic phosphates, and oligomerization products for
      acidic phosphates. Geminal hydroxyl resonance areas displayed significant error
      (4-17%) for low surface area silicas, limiting this method to studies exhibiting
      major changes in chemical or spectroscopic properties.

PMID- 20825949
TI  - Ionic liquid based microemulsion with pharmaceutically accepted components:
      Formulation and potential applications.
AB  - In this paper, we report a novel ionic liquid-in-oil (IL/o) microemulsion which
      is able to dissolve pharmaceuticals that are insoluble or sparingly soluble in
      water and most of pharmaceutical grade organic liquids. Towards this approach,
      the nanometer-sized ionic liquid droplets in isopropyl myristate (IPM) were
      formed with a blend of nonionic surfactants, polyoxyethylene sorbitan monooleate
      (Tween-80), and sorbitan laurate (Span-20). A set of ionic liquids (ILs) was
      tested as a dispersed phase, and it was observed that ILs possessing coordinating
      anions which are strong hydrogen bond acceptor were most effective in forming
      microemulsion droplets. The possible formation mechanism was also studied.
      Ternary phase behavior study clearly indicated the formation of optically
      transparent and thermodynamically stable microemulsions with a wide range of IL
      content. The shape, size and size distribution of the aggregates in
      microemulsions were characterized using dynamic light scattering (DLS), which
      demonstrated the formation of spherical micelles in the range of 8-34nm. In order
      to explore the use of newly developed microemulsion as a potential drug carrier,
      we have investigated the solubility of some drug molecules (e.g., acyclovir,
      methotrexate and 1-[(5-(p-nitrophenyl) furfurylidene) amino] hydantoin sodium)
      that are insoluble or sparingly soluble in most of the conventional solvents.
      Very significantly, the solubility studies indicated a high degree of
      solubilization of such drugs in IL microemulsions. We believe that this
      microemulsion formed with ILs having the unique physical, chemical and biological
      properties may offer novel opportunities to develop a potential drug delivery
      carrier for poorly soluble drugs molecules.

PMID- 20825950
TI  - Electrochemical analysis of azurin thermodynamic and adsorption properties at
      monolayer-protected cluster film assemblies - evidence for a more homogeneous
      adsorption interface.
AB  - Thermodynamic and adsorption properties of protein monolayer electrochemistry
      (PME) are examined for Pseudomonas aeruginosa azurin (AZ) immobilized at an
      electrode modified with a networked film of monolayer-protected clusters (MPCs)
      to assess if nanoparticle films of this nature offer a more homogeneous
      adsorption interface compared to traditional self-assembled monolayer (SAM)
      modified electrodes. Specifically, electrochemistry is used to assess properties
      of surface coverage, formal potential, peak broadening, and electron transfer
      (ET) kinetics as a function of film thickness. The modification of a surface with
      dithiol-linked films of MPCs (Au(225)C6(75)) provides a more uniform binding
      interface for AZ that results in voltammetry with less peak broadening (<110mV)
      compared to SAMs (>120-130mV). Improved homogeneity of the MPC interface for
      protein adsorption is confirmed by atomic force microscopy imaging that shows
      uniform coverage of the gold substrate topography and by electrochemical analysis
      of film properties during systematic desorption of AZ, which indicates a more
      homogeneous population of adsorbed protein at MPC films. These results suggest
      MPC film assemblies may be used in PME to provide greater molecular level control
      of the protein adsorption interface, a development with applications for
      strategies to study biological ET processes as well as the advancement of
      biosensor technologies.

PMID- 20825951
TI  - A new approach for synthesis of the comb-shaped poly (epsilon-caprolactone)
      brushes on the surface of nano-hydroxyapatite by combination of ATRP and ROP.
AB  - A facile strategy for growing the comb-shaped poly (epsilon-caprolactone) brushes
      on the surface of nano-hydroxyapatite (n-HAP) by combination of atom transfer
      radical polymerization (ATRP) and ring-opening polymerization (ROP) would be
      presented. Firstly, ATRP was used to graft poly (2-hydroxyethyl methacrylate)
      (PHEMA) onto the n-HAP surface. Then, the hydroxyl groups introduced onto the n
      HAP were used to initiate the ROP of epsilon-caprolactone for constructing comb
      shaped polymer brushes on the surface of n-HAP. The surface modified n-HAP was
      characterized by Fourier transform infrared (FT-IR) spectra, (13)C solid-state
      cross-polarization magic-angle-spinning ((13)C CP/MAS), and thermal gravimetric
      analysis (TGA), X-ray diffraction (XRD), and transmission electron microscopy
      (TEM) measurements, respectively. The results demonstrated that the comb-shaped
      poly (epsilon-caprolactone) brushes had been grafted successfully, and the
      grafting ratio could be controlled well by adjusting the feed ratio of initiator
      and monomer.

PMID- 20825952
TI  - Ecological Quality Status of the soft-bottom communities on the Algerian coast:
      general patterns and diagnosis.
AB  - Between 1995 and 2001, the soft-bottom communities along the 1180 km of the
      Algerian coast were sampled in nine gulfs and 12 harbours, providing a total of
      655 samples. Eight macrozoobenthos-based biotic indices (S, N, H', BQI, AMBI,
      BENTIX, BO2A and ITI) were selected to describe the general patterns of the
      coastal water quality status and to establish a quality diagnosis for the
      different zones subjected to anthropogenic pressure (e.g., harbour construction,
      industrial and urban pollution). Reference values were determined for each of the
      eight indices selected by analyzing the indices' parameter distribution. The
      Ecological Quality Ratio (EQR) was estimated for each index, resulting in an EQR
      Mean Score and an EQR Bad Score. From these EQR, we defined an EQS for each
      sample. The agreement between these EQS was analysed using the Kappa method in
      order to propose a survey strategy for the Algerian coastal waters that would
      take into account the soft-bottom biological compartment. The results clearly
      indicate that high and good quality assessments are prevalent in the gulfs, while
      quality assessments in harbours vary greatly from bad to good. The effect of
      pollution observed in the harbours can be classified in two main groups,
      according to when they were constructed and their relative degree of openness to
      the sea, which permits better water circulation and probably dilutes the
      pollution.

PMID- 20825953
TI  - Lagrangian particle tracking of a toxic dinoflagellate bloom within the Tampa Bay
      estuary.
AB  - A coastal risk assessment system simulates the basic physical mechanisms
      underlying contaminant transport in Tampa Bay. This risk assessment system,
      comprised of a three-dimensional numerical circulation model coupled to a
      Lagrangian particle tracking model, simulates the transport and dispersion of a
      toxic dinoflagellate bloom. Instantaneous velocity output from the circulation
      model drives the movement of particles, each representing a fraction of a K.
      brevis bloom, within the model grid cells. Hindcast simulations of the spatial
      distribution of the K. brevis bloom are presented and compared with water sample
      concentrations collected during the peak of the bloom. Probability calculations,
      herein called transport quotients, allow for rapid analysis of bay-wide K. brevis
      transport showing locations most likely to be impacted by the contaminant. Maps
      constructed from the transport quotients provide managers with a bay-wide
      snapshot of areas in Tampa Bay most at risk during a hazardous bloom event.

PMID- 20825954
TI  - Comparison of benthic foraminifera and macrofaunal indicators of the impact of
      oil-based drill mud disposal.
AB  - We compare foraminifera and macrofauna as bio-indicators of oil-based drill mud
      disposal site off Congo. The most polluted sites are characterized by poor
      faunas, dominated by some very tolerant taxa. Slightly further from the disposal
      site, there is an area with strongly increased densities, heavily dominated by
      opportunistic taxa. Still further, macrofauna appears to be similar to that at
      the reference area, but the foraminiferal meiofauna still suggests a slight
      environmental perturbation. The foraminiferal FIEI index, based on the species
      distribution in the study area, appears to be more discriminative than the
      macrofaunal ITI index, based on a priori definitions of the trophic guilds of the
      various taxa. Our comparative approach allows us to point out the benefits of (1)
      the use of macrofauna and foraminifera together and (2) the definition of the
      species groups used in biotic indices on the basis of observations made directly
      in the study area.

PMID- 20825955
TI  - Clinical and genetic characteristics of patients with autoimmune thyroid disease
      with anti-islet autoimmunity.
AB  - In contrast to the large number of studies on autoimmunity against the thyroid
      gland in patients with type 1 diabetes mellitus, little is known about the anti
      islet autoimmune status in patients with autoimmune thyroid diseases (AITDs). We
      therefore studied the anti-islet autoimmune status in patients with AITD and the
      clinical and genetic characteristics of AITD patients with anti-islet
      autoimmunity. The positivity and titer of glutamic acid decarboxylase antibody
      (GAD Ab) were studied in 866 Japanese patients with AITD (546 with Graves disease
      and 320 with Hashimoto thyroiditis), 221 patients with thyroid disease of
      nonautoimmune origin, and 282 control subjects. The clinical characteristics and
      genotypes of HLA-DRB1, DQB1, and CTLA4 were compared between AITD patients with
      and without GAD Ab. The prevalence of GAD Ab was significantly higher in AITD
      patients than in control subjects (5.8% vs 2.1%, P = .01), particularly in Graves
      disease (7.1% vs 2.1%, P = .0019). The prevalence of diabetes mellitus was
      significantly higher in AITD patients with GAD Ab than in those without (40.0% vs
      10.1%, P < .0001), particularly in those with a high titer of GAD Ab (high vs low
      titer: 64% vs 16%, P = .001) and also in those positive for insulinoma-associated
      antigen 2 (IA-2) Ab (IA-2 positive vs negative: 75.0% vs 31.3%, P = .016). The
      AITD patients with GAD Ab were characterized by younger age at onset of diabetes,
      lower body mass index, higher hemoglobin A(1c) level, and higher frequency of
      insulin therapy than those without GAD Ab. The frequency of the DRB1*0405
      DQB1*0401 haplotype was significantly higher in AITD patients with GAD Ab than in
      those without GAD Ab and control subjects. A single nucleotide polymorphism
      (rs3087243) of CTLA4 was significantly associated with AITD, but not with
      positivity of GAD Ab. These results indicate that patients with AITD, and in
      particular Graves disease, are prone to develop beta-cell autoimmunity and
      insulin-requiring diabetes, particularly those with a high titer of GAD Ab and/or
      positive for both GAD and IA-2 Ab. Glutamic acid decarboxylase Ab positivity in
      AITD patients was associated with HLA, conferring susceptibility to type 1
      diabetes mellitus.

PMID- 20825956
TI  - Vacuolar and cytosolic cytokinin dehydrogenases of Arabidopsis thaliana:
      heterologous expression, purification and properties.
AB  - The catabolism of cytokinins is a vital component of hormonal regulation,
      contributing to the control of active forms of cytokinins and their cellular
      distribution. The enzyme catalyzing the irreversible cleavage of N(6)-side chains
      from cytokinins is a flavoprotein classified as cytokinin dehydrogenase (CKX, EC
      1.5.99.12). CKXs also show low cytokinin oxidase activity, but molecular oxygen
      is a comparatively poor electron acceptor. The CKX gene family of Arabidopsis
      thaliana comprises seven members. Four code for proteins secreted to the
      apoplast, the remainder are not secreted. Two are targeted to the vacuoles and
      one is restricted to the cytosol. This study presents the purification and
      characterization of each of these non-secreted CKX enzymes and substrate
      specificities are discussed with respect to their compartmentation. Vacuolar
      enzymes AtCKX1 and AtCKX3 were produced in Pichia pastoris and cytosolic enzyme
      AtCKX7 was expressed in Escherichia coli. The recombinant proteins were purified
      by column chromatography. All enzymes preferred synthetic electron acceptors over
      oxygen, namely potassium ferricyanide and 2,3-dimetoxy-5-methyl-1,4-benzoquinone
      (Q(0)). In slightly acidic conditions (pH 5.0), N(6)-(2-isopentenyl)adenine 9
      glucoside (iP9G) was the best substrate for AtCKX1 and AtCKX7, whereas AtCKX3
      preferentially degraded N(6)-(2-isopentenyl)adenine 9-riboside-5'-monophosphate
      (iPMP). Moreover, vacuolar AtCKX enzymes in certain conditions degraded N(6)-(2
      isopentenyl)adenine di- and triphosphates two to five times more effectively than
      its monophosphate.

PMID- 20825957
TI  - [Quadrature coils for magnetic resonance spectroscopy in the detection of
      prostate cancer: single voxel acquisition does not improve the diagnostic
      accuracy of multivoxel images].
AB  - OBJECTIVE: To determine the viability of quadrature coils for detecting prostate
      cancer using single voxel and multivoxel spectroscopy images. MATERIAL AND
      METHODS: We used a quadrature coil on a 1.5T MR scanner to evaluate 23 patients
      with suspected prostate cancer and prostate specific antigen levels greater than
      4ng/ml (mean 12+/-8ng/ml), independently of findings at digital rectal
      examination. We acquired T2-weighted images and MR spectroscopy images. We also
      acquired single voxel studies in areas in which the T2-weighted images or the
      multivoxel images were altered. We used a citrate solution to verify the
      spectroscopic calibration. RESULTS: Using spectroscopy images and a (Co+Cr)/Cit
      cutoff of 1.40 in single voxel spectroscopy, we achieved a sensitivity of 92%,
      specificity of 55%, a negative predictive value of 86%, and a positive predictive
      value of 69%. Using a cutoff of 0.75 decreased specificity slightly (45%). The
      (Co+Cr)/Cit ratio calculated for the single volume obtained from the most
      abnormal area in the T2-weighted images and in the multivoxel spectroscopy slices
      was not significantly different between cancerous and non-cancerous tissues
      (ANOVA, p=0.1), although there was a clear trend toward increased coefficients
      with hyperplasia and neoplastic degeneration. CONCLUSION: The quadrature coil
      enables multivoxel and single voxel spectroscopic images of clinically and
      technically acceptable quality to be obtained. Using single voxel spectroscopy
      does not improve the diagnostic performance of multivoxel spectroscopy and T2
      weighted images.

PMID- 20825958
TI  - [Opportunities for biomedical imaging research in Europe].

PMID- 20825960
TI  - A simple and rapid method for isolation of caliciviruses from liver of infected
      rabbits.
AB  - Rabbit Haemorrhagic Disease Virus (RHDV), a member of the Caliciviridae family,
      is the etiologic agent of Rabbit Haemorrhagic Disease (RHD); this viral disease
      is highly contagious and kills more than 90% of infected adult rabbits. Research
      on experimental calicivirus infection uses inocula obtained from livers of
      rabbits dying from calicivirus infection. This implies that caliciviruses have to
      be purified from liver homogenates. Current methods to isolate caliciviruses from
      rabbit livers are time consuming. We propose here a new procedure for fast
      purification of rabbit caliciviruses from liver homogenates that uses
      centrifugation through an iodixanol gradient. This method offers in approximately
      2 h a sample with a high degree of calicivirus purity, as shown by its
      biochemical and immunocytochemistry analysis, which is also able to kill adult
      rabbits from RHD within 48 h of inoculation.

PMID- 20825959
TI  - Yeast extract, brewer's yeast and spirulina in diets for Labeo rohita fingerlings
      affect haemato-immunological responses and survival following Aeromonas
      hydrophila challenge.
AB  - A feeding trial was conducted for 60 days to study the immunomodulatory role of
      three different immunostimulants yeast extract (YE), brewer's yeast (BY) and
      spirulina (SP) in Labeo rohita fingerlings. Four hundred and fifty fingerlings
      (avg. wt 3.35+/-0.15 g) were randomly distributed in ten treatments and fed with
      either of ten iso-nitrogenous and iso-caloric semi-purified diets, prepared with
      three incremental levels (1%, 2% and 4%) of different immunostimulants except the
      control. Growth parameters did not vary significantly (p>0.05) among the
      experimental groups. Haematology and serum parameters was performed before
      Aeromonas hydrophila challenge whereas respiratory burst activity was analysed
      following challenge. The respiratory burst activity, total leucocyte count, serum
      total protein and globulin was significantly higher (p<0.05) in YE 1%
      supplemented group. The survival (%) after challenging with A. hydrophila was
      also highest in the YE fed groups. The results indicate that among the different
      sources and levels of immunostimulants, YE at lower inclusion level is more
      effective in promoting the immune status of L. rohita fingerlings.

PMID- 20825961
TI  - Effects of a novel ultrasound contrast agent with long persistence on right
      ventricular pressure: Comparison with SonoVue.
AB  - This work investigated the effect of infusion of a self-made ultrasound contrast
      agent with long persistence (named ZHIFUXIAN) on rat right ventricular pressure
      and made a preliminary evaluation on the relative safety of the novel
      microbubbles. Normal saline, SonoVue and ZHIFUXIAN were injected through caudal
      vein at the total volume of 0.5ml for each injection. The right ventricular
      systolic pressure (RVSP) and end-diastolic pressure (RVEDP) were monitored and
      the changes of the pressure were compared with baseline readings. RVSP increased
      when saline, SonoVue or ZHIFUXIAN were injected, the greatest change being after
      SonoVue (about 2mmHg), but there was no statistical significance compared with
      baseline (P>0.05). There was no significant difference in RVSP between saline,
      SonoVue and ZHIFUXIAN at any time point. Also, there was no significant
      difference in RVEDP between groups at each time point and between different time
      points in each group. The results indicate that the self-made microbubbles effect
      on right ventricular hemodynamics is equivalent to that of normal saline at the
      same volume needed for effective enhanced imaging, demonstrating that it does not
      produce changes in right ventricular blood pressure under the study conditions.
      Pathological examination also showed it had no obvious influence on lung, liver
      and kidney.

PMID- 20825962
TI  - Fragmentation of the Golgi apparatus provides replication membranes for human
      rhinovirus 1A.
AB  - All viruses with a positive-stranded RNA genome replicate their genomic RNA in
      association with membranes from the host cell. Here we demonstrate a novel
      organelle source of replication membranes for human rhinovirus 1A (HRV-1A). HRV
      1A infection induces fragmentation of the Golgi apparatus, and Golgi membranes
      are rearranged into vesicles of approximately 250-500 nm diameter. The newly
      distributed Golgi membranes co-localize with viral RNA replication templates,
      strongly suggesting that the observed vesicles are the sites of viral RNA
      replication. Expression of the HRV-1A 3A protein induces alterations in the Golgi
      staining pattern similar to those seen during viral infection, and expressed 3A
      localizes to the Golgi-derived membranes. Taken together, these data show that in
      HRV-1A infection, the 3A protein plays a role in fragmenting the Golgi complex
      and generating vesicles that are used as the site of viral RNA replication.

PMID- 20825963
TI  - Exploring the background features of acidic and basic air pollutants around an
      industrial complex using data mining approach.
AB  - Air pollution data around a monitored site are normally difficult to analyze due
      to highly inter-related meteorological and topographical factors on top of many
      complicated atmospheric chemical interactions occurred in local and regional wind
      fields. The challenge prompts this study to develop a comprehensive data-mining
      algorithm of cluster analysis followed by meteorological and interspecies
      correlations to mitigate the inherent data complexity and dissimilarity. This
      study investigated the background features of acidic and basic air pollutants
      around a high-tech industrial park in Taiwan. Monthly samplings were taken at 10
      sites around the park in a year. The temporal distribution plots show a baseline
      with two characteristic groups of high and low peaks. Hierarchical cluster
      analysis confirms that high peaks were primarily associated with low speed south
      wind in summer for all the chemical species, except for F(-), Cl(-), NH(3) and
      HF. Crosschecking with the topographical map identifies several major external
      sources in south and southwest. Further meteorological correlation suggests that
      HCl is highly positively associated with humidity, while Cl(-) is highly
      negatively associated with temperature, both for most stations. Interestingly,
      HNO(3) is highly negatively associated with wind speed for most stations and the
      hotspot was found in summer and around the foothill of Da-Tu Mountain in the
      northwest, a stagnant pocket on the study site. However, F(-) is highly
      positively associated with wind speed at downwind stations to the prevailing
      north wind in winter, indicating an internal source from the north. The presence
      of NH(4)(+) stimulates the formation of NO(3)(-), SO(4)(-2) (R=0.7), and HNO(3),
      H(2)SO(4), NH(3) (R=0.3-0.4). As H(2)SO(4) could be elevated to a level as high
      as 40% of the regulated standard, species interactions may be a dominate
      mechanism responsible for the substantial increase in summer from external
      sources.

PMID- 20825964
TI  - Assessing amendment and fertilizing properties of digestates from anaerobic
      digestion through a comparative study with digested sludge and compost.
AB  - Digestate, with biogas represents the final products of anaerobic digestion (AD).
      The methane-rich biogas is used to produce electricity and heat, whereas the
      digestate could be valorized in agriculture. Contrarily to well-recognized
      biomasses such as digested sludge and compost, the properties of the digestate
      are not well known and its agricultural use remains unexplored. In this work, a
      first attempt to study the agronomic properties of digestates was performed by
      comparing the chemical, spectroscopic, and biological characteristics of
      digestates with those of compost and digested sludge, used as reference organic
      matrices. A total of 23 organic matrices were studied, which include eight
      ingestates and relative digestates, three composts, and four digested sludges.
      The analytical data obtained was analyzed using principal component analysis to
      better show in detail similarities or differences between the organic matrices
      studied. The results showed that digestates differed from ingestates and also
      from compost, although the starting organic mix influenced the digestate final
      characteristics. With respect to amendment properties, it seems that biological
      parameters, more than chemical characteristics, were more important in describing
      these features. In this way, amendment properties could be ranked as follows:
      compost?digestate>digested sludge?ingestate. As to fertilizer properties, AD
      allowed getting a final product (digestate) with very good fertilizing properties
      because of the high nutrient content (N, P, K) in available form. In this way,
      the digestate appears to be a very good candidate to replace inorganic
      fertilizers, also contributing, to the short-term soil organic matter turnover.

PMID- 20825965
TI  - Optimization of pig slurry application to heavy metal polluted soils monitoring
      nitrification processes.
AB  - Nitrification is often negatively affected by heavy metal pollution in soils,
      this limiting land revegetation. Thus, the potential use of pig slurry as a
      nitrogen-rich organic amendment in different heavy metal contaminated soils has
      been evaluated; this also being a way of recycling this waste. In order to
      identify the factors affecting nitrification processes in heavy metal polluted
      soils (soil pH, heavy metal solubility and the N source), incubation experiments
      were run using two polluted soils with different pH values (5.0 and 7.1) and a
      non-contaminated soil (pH 8.2). Ammonium was added as pig slurry or as ammonium
      sulphate for comparison (both added at 150 mg NH(4)(+)-N kg(-1) of soil). Pig
      slurry provoked higher nitrification rates and N-immobilisation than ammonium
      sulphate, especially in the neutral-polluted soil, reflecting an improvement of
      the microbial activity in the soil. The microbial immobilisation of N led to an
      inverse relationship between the amount of N added and nitrate conversion in the
      neutral-polluted soil and in the non-contaminated soil amended with different pig
      slurry dosages (75, 150 and 225mg NH(4)(+)-N kg(-1) of soil). Low rates of
      nitrification and N-immobilisation were found in the acidic soil. Pig slurry
      addition to metal polluted soils enhanced soil nitrification, especially when
      metals were in low-solubility forms.

PMID- 20825966
TI  - Potential biochemical and genetic toxicity of triclosan as an emerging pollutant
      on earthworms (Eisenia fetida).
AB  - Triclosan as an important antimicrobial agent is increasingly detected in the
      terrestrial environment as sewage sludge and reclaimed water are applied on land,
      but little is known about its effect on non-target soil organisms. In this study,
      biochemical responses including changes in the activity of catalase (CAT),
      superoxide dismutase (SOD), glutathione-S-transferase (GST), and malondialdehyde
      (MDA) of the earthworm Eisenia fetida were examined in order to assess ecological
      toxicity of the chemical. The single-cell gel electrophoresis (SCGE) was also
      used to measure the potential genotoxicity of the chemical. The results showed
      that the activity of CAT and GST at the highest tested dose could be stimulated
      after a 2-d exposure, reaching 148% and 123% of that in the control,
      respectively. However, with prolonged exposure, the activity of CAT and GST at
      the highest tested dose was inhibited, falling to 47% and 33% of that in the
      control, respectively. Triclosan induced an increase in the activity of SOD, but
      no significant (p>0.05) changes were observed. The content of MDA was dependent
      both on the dose of triclosan and on the exposure duration. The comet assay
      demonstrated that triclosan treatments led to a dose-dependent DNA damage of E.
      fetida after exposures of 7 and 14 d. Our findings can suggest that triclosan has
      sublethal effects on E. fetida.

PMID- 20825967
TI  - Single application of sewage sludge--impact on the quality of an alluvial
      agricultural soil.
AB  - The effects of sewage sludge on soil quality with regard to its nutrient and
      heavy metal content, microbial community structure and ability to maintain
      specific soil function (degradation of herbicide glyphosate) were investigated in
      a three months study using an alluvial soil (Eutric Fluvisol). Dehydrated sewage
      sludge significantly increased soil organic matter (up to 20.6% of initial
      content), total and available forms of N (up to 33% and 220% of initial amount,
      respectively), as well as total and plant available forms of P (up to 11% and
      170% of initial amount, respectively) and K (up to 70% and 47% of initial amount,
      respectively) in the upper 2 cm soil layer. The increase of organic matter was
      most prominent 3d after the application of sewage sludge, after 3 months it was
      no longer significant. Contents of nutrients kept to be significantly higher in
      the sewage sludge treated soil till the end of experiment. Contents of some heavy
      metals (Zn, Cu, Pb) increased as well. The highest increase was found for Zn (up
      to 53% of initial amount), however it was strongly bound to soil particles and
      its total content was kept below the maximum permissible limit for agricultural
      soil. Based on molecular fingerprinting of bacterial 16S rRNA gene and fungal ITS
      fragment on 3rd day and 3rd month after sewage sludge amendment, significant
      short term effects on bacterial and fungal communities were shown due to the
      sewage sludge. The effects were more pronounced and more long-term for bacterial
      than fungal communities. The mineralization of (14)C-glyphosate in the sewage
      sludge soil was 55.6% higher than in the control which can be linked to (i) a
      higher glyphosate bioavailability in sewage sludge soil, which was triggered by
      the pre-sorption of phosphate originating from the sewage sludge and/or (ii)
      beneficial alterations of the sewage sludge to the physical-chemical
      characteristics of the soil.

PMID- 20825968
TI  - Glutathione pathway in ethylbenzene metabolism: novel biomarkers of exposure in
      the rat.
AB  - Glutathione pathway was specifically studied in rats exposed by inhalation to a
      range of ethylbenzene vapours (5-2000 ppm). Urines were collected during exposure
      (6h) and over the 18 h following the exposure. The potential metabolites coming
      from either side-chain or ring oxidation were synthesized: 1-, 2
      phenylethylmercapturic acids (1-, and 2-PEMA) and 2-, 3- and 4
      ethylphenylmercapturic acids (2-, 3-, and 4-EPMA). Their synthesis was fully
      described and the molecules characterized. Urine samples were analysed using a
      selective HPLC-fluorescence method. Among the five metabolites, 2-PEMA was never
      observed in any urine sample. By contrast, 1-PEMA was discovered in its two
      diastereomeric forms, and it was shown that one of them was mainly present. 2
      EPMA, 3-EPMA and 4-EPMA (in the ratio 1:2:6) were also found, and their combined
      excretion levels were similar to that of 1-PEMA. The atmospheric concentrations
      and urinary excretions yielded very close correlations which allow us to consider
      these mercapturic acids as novel ethylbenzene exposure biomarkers.

PMID- 20825969
TI  - Aluminum polymers formed following alum treatment of lake water.
AB  - Alum (aluminum sulfate) is increasingly being used in lake management to control
      internal recycling of phosphorus from bottom sediments. Alum added to water
      undergoes rapid hydrolysis reactions, forming an amorphous Al(OH)3 floc with a
      high capacity for sorption of phosphorus. While it is known that the Al(OH)3 floc
      transforms over time to more ordered microcrystalline and crystalline gibbsite
      phases, there remains an incomplete understanding of the forms of Al present
      immediately following alum addition to lake water. A laboratory study was thus
      undertaken to evaluate the forms of Al present following alum addition using
      ferron (8-hydroxy-7-iodo-5-quinolinesulfonic acid) timed-colorimetric and 27Al
      NMR measurements. A polymeric Al species with moderate reactivity with ferron
      (Alb2) was initially formed, although it rapidly transformed to a less ferron
      reactive colloidal form (Alc) and also decomposed at low alum doses to monomeric
      Al (Ala) in response to pH increases associated with outgassing of CO2. The Ala
      fraction in these solutions could be adequately estimated based upon measured pH
      assuming Al solubility was controlled by an amorphous Al(OH)3 phase. Al13 was
      inferred from ferron measurements to be present, but only at quite low
      concentrations in the alum-treated waters.

PMID- 20825970
TI  - Hexabromocyclododecane determination in seafood samples collected from Japanese
      coastal areas.
AB  - The levels of three hexabromocyclododecane (HBCD) isomers and SigmaHBCDs in 54
      wild and 11 farmed seafood samples collected from four regions of Japan were
      determined by LC/MS/MS. For the fish classified as Anguilliformes, Perciformes,
      Clupeiformes and farmed Salmoniformes, the medians (ranges) of SigmaHBCDs are
      2.09 (0.05-36.9), 0.75 (ND-26.2), 0.12 (0.09-77.3) and 1.29 (1.09-1.34) ng g(
      1)ww, respectively. However, HBCDs were not detected in samples classified as
      Crustacea, Mollusca, Pleuronectiformes and Scorpaeniformes, or if detected, the
      levels were very low. The rank correlation between SigmaHBCDs (or alpha-HBCD) and
      fat content could not be found except for the Japanese sea bass of the Tohoku
      region. In HBCD isomer profiles, for fish samples above 20 ng g(-1)ww, the trend
      was found that gamma-HBCD was predominant, which suggests the influence of
      discharge from a nearby industrial plant. In the other wild fish and the farmed
      fish samples, on the other hand, alpha-HBCD was mostly predominant, which
      suggests biomagnification via the food chain. Additionally, to assess the risk to
      human health, based on the determined HBCD median concentrations for
      Anguilliformes, farmed Salmoniformes and Perciformes, the daily intake of HBCDs
      from fish by an average Japanese adult was tentatively calculated to be 3.7, 2.3
      and 1.3 ng (kg body weight)(-1) d(-1), respectively.

PMID- 20825971
TI  - Absence of markers of betaretrovirus infection in human pulmonary adenocarcinoma.
AB  - A proportion of human pulmonary adenocarcinomas has been shown previously to
      express an antigen related to the Gag protein of a betaretrovirus, Jaagsiekte
      sheep retrovirus, that causes ovine pulmonary adenocarcinoma. To investigate
      further the hypothesis that a retrovirus might be present in human lung
      adenocarcinoma, we examined specimens from patients with lung cancer for evidence
      of retroviral infection by immunohistochemistry, reverse transcriptase-polymerase
      chain reaction, immunoblotting and cDNA library screening. Thirty-eight percent
      of the tumor samples analyzed were positive by immunohistochemistry for Gag
      related antigen of Jaagsiekte sheep retrovirus. However, this antigen was not
      detected by immunoblotting using the same antiserum. In addition, plasma samples
      from the patients did not contain antibodies reacting with Gag proteins from
      Jaagsiekte sheep retrovirus or other betaretroviruses on immunoblots. Reverse
      transcriptase-polymerase chain reaction identified the expression of endogenous
      betaretroviruses in tumor tissue and in normal lung tissue, but no specific
      provirus was associated with tumor. Expression library screening did not identify
      the Gag-reactive antigen. This study has confirmed the expression of a Jaagsiekte
      sheep retrovirus Gag-related antigen in some human lung tumors but additional
      evidence of betaretroviral infection was not obtained. While these data do not
      rule out a role for a retrovirus in human pulmonary adenocarcinomas, they suggest
      that, if such a virus is present, it is unrelated to known betaretroviruses.

PMID- 20825972
TI  - Expression of ribonucleotide reductase M2 subunit in gastric cancer and effects
      of RRM2 inhibition in vitro.
AB  - Ribonucleotide reductase M2 subunit is one of two subunits that constitute
      ribonucleotide reductase, the enzyme that catalyzes the conversion of
      ribonucleotide 5'-diphosphates into 2'-deoxyribonucleotides, which are required
      for DNA synthesis. This study was conducted to investigate the roles of
      ribonucleotide reductase M2 subunit in gastric cancer. The expression of
      ribonucleotide reductase M2 subunit protein was examined by immunohistochemistry.
      In normal gastric mucosa, ribonucleotide reductase M2 subunit expression was
      restricted to the neck regions of gastric pits and no expression was observed in
      the surface epithelium. Among 112 gastric cancer tissues, ribonucleotide
      reductase M2 subunit overexpression (>=10% cancer cells stained) was observed in
      72 cases (64.3%). Ribonucleotide reductase M2 subunit overexpression was
      significantly associated with male sex (P = .015), presence of muscularis propria
      invasion (P = .020), presence of Epstein-Barr virus (P = .045), expression of
      survivin (P = .0014), and DNA methyltransferase 1 (P = .043), but not with age,
      histology, tumor size, lymph node metastasis or expression of phosphatase and
      tensin homolog, phosphorylated signal transducer, and activator of transcription
      3 or p53. Suppression of ribonucleotide reductase M2 subunit synthesis, using
      small interfering RNA, inhibited the growth of 3 gastric cancer cell lines, MKN
      1, MKN-7, and SNU-719. Our data suggest that ribonucleotide reductase M2 subunit
      overexpression could be associated with the gastric cancer progression and that
      suppression of its function is a potential therapeutic strategy in gastric
      cancer.

PMID- 20825973
TI  - Matrix metalloproteinase 9 is associated with Gleason score in prostate cancer
      but not with prognosis.
AB  - Prostate cancer is the most common cancer in North American men. Among men
      diagnosed with prostate cancer in more than three cores or with high grade
      prostate cancer, many experience long disease-free survival. However, these
      patients still undergo radical treatment while they could benefit from active
      surveillance with complementary therapy. Matrix metalloproteinase 9 degrades type
      IV collagen and activates tumorigenic factors and is thus a potential prognostic
      factor and therapeutic target. This study was thus aimed at investigating the
      role of matrix metalloproteinase 9 on prostate cancer progression. We correlated
      matrix metalloproteinase 9 immunohistochemical expression by cancer, stromal and
      benign epithelial cells with prostate cancer disease-free survival among a cohort
      composed of 187 pT3NxM0 prostate cancer patients. Median follow-up was 4.63 years
      and a recurrence occurred in 67 men (35.3%). Matrix metalloproteinase 9
      immunostaining was cytoplasmic and expressed at different levels in cancer
      (94.1%), stromal (87.7%) and benign epithelial cells (94.1%). High levels (>50%
      of cells) of matrix metalloproteinase 9 expression by prostate cancer cells was
      strongly associated with high Gleason score (P = .0009). In stromal cells and in
      benign epithelial cells, high matrix metalloproteinase 9 expression levels were
      respectively associated with low pT3 substage (P = .046) and with low initial
      serum prostate-specific antigen levels (P = .006). Matrix metalloproteinase 9
      expression level by any cell type was not associated with prostate cancer disease
      free survival. These results show that matrix metalloproteinase 9 is
      overexpressed by cancer cells in high grade tumors and by stromal and benign
      epithelial cells in lower substage tumors.

PMID- 20825974
TI  - Programmed death 1 expression in variant immunoarchitectural patterns of nodular
      lymphocyte predominant Hodgkin lymphoma: comparison with CD57 and lymphomas in
      the differential diagnosis.
AB  - Recent studies have exploited an antibody directed against programmed death 1
      expressed by follicular helper T-cells in the diagnosis of nodular lymphocyte
      predominant Hodgkin lymphoma. We had previously described clinically relevant,
      variant immunoarchitectural patterns of nodular lymphocyte predominant Hodgkin
      lymphoma and, in this study, sought to address the diagnostic utility of
      programmed death 1 in comparison with CD57 in variant nodular lymphocyte
      predominant Hodgkin lymphoma. Immunohistologic staining for programmed death 1
      was carried out on biopsies of 67 patients with variant nodular lymphocyte
      predominant Hodgkin lymphoma. Thirty-four additional cases of nodular lymphocyte
      predominant Hodgkin lymphoma with associated diffuse areas, de novo T-cell and
      histiocyte-rich large B-cell lymphoma, and lymphocyte-rich classic Hodgkin
      lymphoma were also studied. Our results show that programmed death 1 positivity
      was found in the majority of nodular lymphocyte predominant Hodgkin lymphoma
      cases with a classic nodular architecture (87%) as compared with 50% for CD57 and
      was particularly helpful in identifying extranodular large atypical cells.
      Nodular lymphocyte predominant Hodgkin lymphoma with diffuse areas showed a
      gradual decrease in programmed death 1 reactivity from nodular to diffuse areas,
      although a significant proportion (40%-50%) of cases retained programmed death 1
      positivity also in diffuse areas. In addition, T-cell and histiocyte-rich large B
      cell lymphoma and lymphocyte-rich classic Hodgkin lymphoma displayed programmed
      death 1 positivity in a significant subset of cases (33%-40%). In conclusion, our
      study supports the utility of programmed death 1 in the diagnosis of nodular
      lymphocyte predominant Hodgkin lymphoma and shows greater sensitivity of staining
      of programmed death 1 as compared with CD57 across all variants of nodular
      lymphocyte predominant Hodgkin lymphoma. Loss of programmed death 1 reactivity
      did not correlate with diffuse areas, progression, or the ability to
      differentiate nodular lymphocyte predominant Hodgkin lymphoma from T-cell and
      histiocyte-rich large B-cell lymphoma. These findings suggest the need for
      continued vigilance in the diagnosis of nodular lymphocyte predominant Hodgkin
      lymphoma and its immunoarchitectural variants as well as related lymphomas in
      their differential diagnosis.

PMID- 20825975
TI  - Association between blood lead levels (<5 MUg/dL) and inattention-hyperactivity
      and neurocognitive profiles in school-aged Korean children.
AB  - OBJECTIVES: The association between low blood lead levels (<5 MUg/dL) and the
      inattention-hyperactivity symptoms and neurocognitive profiles of school-aged
      Korean children was investigated. METHODS: We measured blood lead levels in 256
      Korean children aged 8-10 years. Teachers completed the Attention-Deficit
      Hyperactivity Disorder Rating Scale (T-ARS)-IV to assess inattentive and
      hyperactive symptoms. Parents completed the Korean version of the Learning
      Disability Evaluation Scale (K-LDES). Children performed neurocognitive tests
      [The Continuous Performance Test (CPT), the Children's Color Trails Test, and the
      Stroop Color and Word Test (SCWT)]. RESULTS: A linear regression analysis
      indicated that the blood lead concentrations were associated with the inattention
      scores [B=4.8, S.E.=1.6, 95% confidence interval (CI): 1.5-8.0], the
      hyperactivity subscores (3.1, 1.4, 0.3-5.9), and the total score (7.9, 2.9, 2.1
      13.6) on the T-ARS; the number of omission errors on the CPT (20.6, 7.1, 6.5
      34.6); the listening (-1.4, 0.7, -2.8 to -0.1), reading (-2.1, 0.7, -3.4 to 
      0.7), writing (-2.0, 0.7, -3.4 to -0.6), spelling (-2.2, 0.7, -3.7 to -0.7), and
      calculating (-1.8, 0.7, -3.1 to -0.4) scores on the K-LDES; and the color-word
      score on the SCWT (-6.7, 3.4, -13.3 to -0.1). A logistic regression analysis
      indicated that the probability of inattentive and hyperactive symptoms was
      increased with higher blood lead levels in boys with an odds ratio of 2.768
      [B=1.018, S.E.=0.487, p=0.036, 95% CI: 1.066-7.187]. CONCLUSION: This study
      suggests that even low blood lead levels (<5 MUg/dL) are associated with
      inattentive and hyperactivity symptoms and learning difficulties in school-aged
      children.

PMID- 20825976
TI  - Short-term effect of fine particulate matter (PM 2.5) on daily mortality due to
      diseases of the circulatory system in Madrid (Spain).
AB  - INTRODUCTION: Owing to their small size, fine particles, i.e., those having a
      diameter <= 2.5 MUm (PM(2.5)), have a high alveolar penetration capacity, thereby
      triggering a local inflammatory process with circulatory repercussion. Despite
      being linked to respiratory and cardiovascular morbidities, there is limited
      evidence of an association between this type of particulate matter and short-term
      increases in mortality. OBJECTIVE: The aim of this study was to analyse and
      quantify the short-term impact of PM(2.5) on daily mortality due to diseases of
      the circulatory system, registered in Madrid from 1 January 2003 to 31 December
      2005. METHODS: An ecological longitudinal time-series study was conducted, with
      risks being quantified by means of Poisson regression models. As a dependent
      variable, we took daily mortality registered in Madrid from 1 January 2003 to 31
      December 2005, attributed to all diseases of the circulatory system as classified
      under heads I00-I99 of the International Classification of Diseases-10th revision
      (ICD-10) and broken down as follows: I21, acute myocardial infarction (AMI); I20,
      I22-I25, other ischemic heart diseases; and I60-I69, cerebrovascular diseases.
      The independent variable was daily mean PM(2.5) concentration. The other
      variables controlled for were: chemical pollution (PM(10), O(3), SO(2), NO(2) and
      NO(x)); acoustic and biotic pollution; influenza; minimum and maximum
      temperatures; seasonalities; trend; and autocorrelation of the series. RESULTS: A
      linear relationship was observed between PM(2.5) levels and mortality due to
      diseases of the circulatory system. For every increase of 10 MUg/m(3) in daily
      mean PM(2.5) concentration, the relative risks (RR) were as follows: for overall
      circulatory mortality, associations were established at lags 2 and 6, with RR of
      1.022 (1.005-1.039) and 1.025 (1.007-1.043) respectively; and for AMI mortality,
      there was an association at lag 6, with an RR of 1.066 (1.032-1.100). The
      corresponding attributable risks percent (AR%) were 2.16%, 2.47% and 6.21%
      respectively. No statistically significant association was found with other
      ischemic heart diseases or with cerebrovascular diseases. CONCLUSION: PM(2.5)
      concentrations are an important risk factor for daily circulatory-cause mortality
      in Madrid. From a public health point of view, the planning and implementation of
      specific measures targeted at reducing these levels constitute a pressing need.

PMID- 20825977
TI  - Perinatal lead and mercury exposure in Austria.
AB  - OBJECTIVE: The heavy metals lead (Pb) and mercury (Hg) are ubiquitous
      environmental pollutants with high neurotoxic potential. We aimed to compare
      perinatal Pb and Hg concentrations and to explore the potential association
      between Pb and Hg exposure and newborn anthropometry. STUDY DESIGN: Pregnant
      women were recruited in 2005 at the General Hospital Vienna for participation in
      this longitudinal study. Pb and Hg concentrations were measured in maternal blood
      and hair, placenta, cord blood, meconium, and breast milk of 53 mother-child
      pairs by CV-AAS, GF-AAS, and HPLC-CV-ICPMS. We conducted bivariate analyses and
      categorical regression analysis (CATREG) to evaluate the determinants of Pb and
      Hg exposure, and of infant anthropometry. RESULTS: Median Pb and total Hg
      contents were low, i.e., 25 MUg/L (maternal blood-Pb), 13 MUg/L (cord blood-Pb),
      0.7 MUg/L (maternal blood-Hg), and 1.1 MUg/L (cord blood-Hg). Hg levels in
      maternal and fetal tissues were frequently correlated (r>0.3, P<0.05,
      respectively). Regarding Pb, only maternal blood and cord blood concentrations
      correlated (P=0.043). Cord blood levels indicated higher Hg exposure but lower Pb
      exposure relative to maternal blood contents. Adjusted CATREG models indicated
      the significant predictors of birth length (placenta-Pb, gestational length,
      meconium-Pb), birth weight (placenta-Pb, gestational length, maternal blood-Pb),
      and head circumference (maternal education, maternal height). Besides one
      significant correlation between maternal hair Hg and birth length, the mercury
      levels were not associated with newborn anthropometry. CONCLUSIONS: Our data
      implicate that different modes of action may exist for placentar transfer of Pb
      and Hg as well as that low Pb exposure levels can result in lower birth weight.
      The findings related to newborn anthropometry need to be confirmed by the
      examination of larger study groups. Further research is needed to clarify the
      mechanisms of Pb and Hg transfer via the placenta, and to explore how prenatal Pb
      exposure is related to intrauterine growth.

PMID- 20825978
TI  - Environment and T regulatory cells in allergy.
AB  - The central role of T regulatory cells in the responses against harmless
      environmental antigens has been confirmed by many studies. Impaired T regulatory
      cell function is implicated in many pathological conditions, particularly
      allergic diseases. The "hygiene hypothesis" suggests that infections and
      infestations may play a protective role for allergy, whereas environmental
      pollutants favor the development of allergic diseases. Developing countries
      suffer from a variety of infections and are also facing an increasing diffusion
      of environmental pollutants. In these countries allergies increase in relation to
      the spreading use of xenobiotics (pesticides, herbicides, pollution, etc.) with a
      rate similar to those of developed countries, overcoming the protective effects
      of infections. We review here the main mechanisms of non-self tolerance, with
      particular regard to relations between T regulatory cell activity, infections and
      infestations such as helminthiasis, and exposure to environmental xenobiotics
      with relevant diffusion in developing countries.

PMID- 20825979
TI  - Naphthenic acids and other acid-extractables in water samples from Alberta: what
      is being measured?
AB  - There is increasing international interest in naphthenic acids (NAs, classical
      formula C(n)H(2n+Z)O(2)) found in the oil sands from Alberta, Canada and in
      petroleum from around the world. The complexity of NAs poses major analytical
      challenges for their quantification and characterization. We used ultrahigh
      resolution electrospray ionization Fourier transform ion cyclotron resonance mass
      spectrometry (ESI-FT-ICR MS) to probe the make up of NAs from various sources by
      searching for peaks corresponding to the formula C(n)H(2n+Z)O(x), for
      combinations of n=8 to 30, Z=0 to -12, and x=2 to 5. The sources included three
      commercial NAs preparations, and the acid-extractable organics from eight oil
      sand process-affected waters (OSPW) and from six surface fresh waters. Extracts
      from OSPW contained between 1 and 7% sulfur. The mass spectra showed between 300
      and 1880 peaks, with >99% of the peaks having m/z between 145 and 600. In most
      cases, <20% of the peaks were assigned as classical NAs (x=2) and oxy-NAs (x=3 to
      5). The classical NAs from the OSPW were predominantly Z=-4 and -6, whereas those
      from the fresh waters were mainly Z=0, with palmitic and stearic acids being the
      major components in the fresh waters. Remarkably, when the peak abundances were
      considered, <50% of the total abundance could be assigned to the classical and
      oxy-NAs. Thus, >50% of the compounds in the extracts of OSPW were not "naphthenic
      acids". Based on these findings, it appears that the term "naphthenic acids",
      which has been used to describe the toxic extractable compounds in OSPW, should
      be replaced by a term such as "oil sands tailings water acid-extractable organics
      (OSTWAEO)". Classical and oxy-NAs are components of OSTWAEO, but this term would
      not be as misleading as "naphthenic acids".

PMID- 20825980
TI  - Environmental implications of water efficient microcomponents in residential
      buildings.
AB  - The Code for Sustainable Homes (CSH) in England sets out various water efficiency
      targets/levels, which form part of environmental performance criteria against
      which the sustainability of a building is measured. The code is performance based
      and requires reduction in per capita water consumption in households. The water
      efficiency related targets can be met using a range of water efficient
      microcomponents (WC, showers, kitchen taps, basin taps, dishwashers, washing
      machines, and baths). However, while the CSH aims at reducing the adverse
      environmental implications associated with the dwellings by promoting reduction
      in water consumption, little is known about the energy consumption and the
      environmental impacts (e. g. carbon emissions) resulting from water efficient end
      uses. This paper describes a methodology to evaluate the energy consumption and
      carbon emissions associated with the CSH's water efficiency levels. Key findings
      are that some 96% and 87% of energy use and carbon emissions, respectively
      associated with urban water provision are attributable to in-house consumption
      (principally related to hot water), and that achieving a defined water efficiency
      target does not automatically save energy or reduce carbon emissions.

PMID- 20825981
TI  - Flow cytometry-evaluated platelet CD36 expression, reticulated platelets and
      platelet microparticles in essential thrombocythaemia and secondary
      thrombocytosis.

PMID- 20825982
TI  - Hepatitis C virus seropositivity and TNF superfamily receptors: sCD40, sFas--the
      new putative determinants of endothelial dysfunction in haemodialysis patients.
AB  - INTRODUCTION: Hepatitis C virus (HCV) infection occurs frequently among
      haemodialysis (HD) patients and increases the risk of atherosclerosis. CD40 and
      Fas belong to tumor necrosis factor receptor (TNFR) superfamily, which play a
      role in hepatocyte apoptosis during HCV infection. The aim of the present study
      was to determine whether anti-HCV-seropositivity constitutes an additional risk
      factor for endothelial dysfunction in HD patients, and whether sCD40 and sFas
      could be associated with endothelial dysfunction. MATERIALS AND METHODS: A total
      of 69 stable HD patients and 28 healthy controls were included in this study.
      Patients were divided into anti-HCV-seropositive (HCV[+], n=18) and anti-HCV-
      seronegative (HCV[-], n=51). The plasma endothelial markers: von Willebrand
      factor (vWF), thrombomodulin (TM), soluble adhesion molecules - sICAM-1, sVCAM-1
      and TNFRs were assayed. RESULTS: HD patients showed a significant increase in the
      levels of TM, sVCAM-1, sCD40 and sFas compared to controls, and all these
      parameters were higher in HCV[+] than in HCV[-] patients. sICAM-1 concentrations
      were higher in the HCV[+] group compared to controls and the HCV[-] group. vWF
      levels were higher in HD patients than in the controls, however there was no
      difference in this parameter between HCV[+] and HCV[-] group. The anti-HCV
      seropositivity and sCD40 were determined as an independent variables of TM,
      whereas anti-HCV-seropositivity and sFas were found as independent determinants
      of sICAM-1 and sVCAM-1 levels. CONCLUSIONS: This study showed that anti-HCV
      seropositivity and TNF superfamily receptors: sCD40 and sFas are the novel
      determinants of the increased plasma endothelial dysfunction markers in
      haemodialysis patients.

PMID- 20825983
TI  - Comparison of rosuvastatin and atorvastatin on clopidogrel response and lipidic
      and inflammatory parameters after coronary stenting for acute coronary syndrome:
      the prospective, randomized OSCAR study (optimal statin therapy with clopidogrel
      after coronary revascularisation).

PMID- 20825984
TI  - Suberoylanilide hydroxamic acid partly reverses resistance to paclitaxel in human
      ovarian cancer cell lines.
AB  - OBJECTIVES: The purpose of this study was to determine whether the addition of
      the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) to
      paclitaxel (PTX) can sensitize PTX-resistant human ovarian cancer cell lines
      (CABA-PTX and IGROV-PTX) in vitro. METHODS: SAHA was studied in combination with
      paclitaxel in PTX-sensitive and PTX-resistant human ovarian cancer cell lines.
      Using cell proliferation analysis, immunofluorescence, and flow cytometric
      assays, we can determine whether the resistance was partly removed when the cells
      were treated with a combination of SAHA and PTX. Cells were also assayed for
      cytochrome c release. The levels of acetylated tubulin, beta-tubulin, and HDAC6
      were quantified by Western blots. RESULTS: SAHA in combination with PTX led to a
      more pronounced inhibition of cell growth compared with PTX alone. In addition,
      the combined exposure to PTX and SAHA resulted in a marked arrest in the G2/M
      phase of the cell cycle and in a significant increase in the percentage of
      apoptotic cells. The expression of acetylated tubulin was dramatically increased
      by exposure to the combination of PTX and SAHA. These data paralleled the
      findings of an increased expression of HDAC6 in the presence of PTX in PTX
      resistant cell lines. CONCLUSIONS: The results of this study suggest the
      existence of a novel resistance mechanism based upon the upregulation of HDAC6
      and that the histone deacetylase inhibitor SAHA holds promise to overcome PTX
      resistance in ovarian cancer cell lines.

PMID- 20825985
TI  - Celiprolol therapy for vascular Ehlers-Danlos syndrome.

PMID- 20825986
TI  - Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers
      Danlos syndrome: a prospective randomised, open, blinded-endpoints trial.
AB  - BACKGROUND: Vascular Ehlers-Danlos syndrome is a rare severe disease that causes
      arterial dissections and ruptures that can lead to early death. No preventive
      treatment has yet been validated. Our aim was to assess the ability of
      celiprolol, a beta(1)-adrenoceptor antagonist with a beta(2)-adrenoceptor agonist
      action, to prevent arterial dissections and ruptures in vascular Ehlers-Danlos
      syndrome. METHODS: Our study was a multicentre, randomised, open trial with
      blinded assessment of clinical events in eight centres in France and one in
      Belgium. Patients with clinical vascular Ehlers-Danlos syndrome were randomly
      assigned to 5 years of treatment with celiprolol or to no treatment.
      Randomisation was done from a centralised, previously established list of sealed
      envelopes with stratification by patients' age (<=32 years or >32 years). 33
      patients were positive for mutation of collagen 3A1 (COL3A1). Celiprolol was
      administered twice daily and uptritrated by 100 mg steps every 6 months to a
      maximum of 400 mg per day. [DOSAGE ERROR CORRECTED]. The primary endpoints were
      arterial events (rupture or dissection, fatal or not). This study is registered
      with ClinicalTrials.gov, number NCT00190411. FINDINGS: 53 patients were randomly
      assigned to celiprolol (25 patients) or control groups (28). Mean duration of
      follow-up was 47 (SD 5) months, with the trial stopped early for treatment
      benefit. The primary endpoints were reached by five (20%) in the celiprolol group
      and by 14 (50%) controls (hazard ratio [HR] 0.36; 95% CI 0.15-0.88; p=0.040).
      Adverse events were severe fatigue in one patient after starting 100 mg
      celiprolol and mild fatigue in two patients related to dose uptitration.
      INTERPRETATION: We suggest that celiprolol might be the treatment of choice for
      physicians aiming to prevent major complications in patients with vascular Ehlers
      Danlos syndrome. Whether patients with similar clinical presentations and no
      mutation are also protected remains to be established. FUNDING: French Ministry
      of Health, Programme Hospitalier de Recherche Clinique 2001.

PMID- 20825987
TI  - Golden grey mullet and sea bass oxidative DNA damage and clastogenic/aneugenic
      responses in a contaminated coastal lagoon.
AB  - Several xenobiotics or their metabolites have redox-cycling properties and
      potential to induce oxidative stress and DNA damage. The current work aimed to
      study, under environmental conditions, oxidative DNA damage (8-hydroxy-2'
      deoxyguanosine (8-OHdG)) and its association with chromosomal damage measured as
      erythrocytic nuclear abnormalities (ENAs), in Liza aurata and Dicentrarchus
      labrax, caught at a costal lagoon (Ria de Aveiro, Portugal) having sites with
      different contamination profiles. The quantified parameters were also used to
      assess the lagoon's environmental status. Five critical sites were assessed
      comparing to a reference site. L. aurata displayed higher 8-OHdG levels and ENAs
      frequency, respectively, at Laranjo and Vagos. D. labrax 8-OHdG levels were
      higher at the sites where quantification was possible whereas no differences were
      found in terms of ENAs. No correlation was found in both species between 8-OHdG
      and ENAs. Despite no direct linkage between the two biomarkers was found, this
      study demonstrates species and site dependent genotoxic responses.

PMID- 20825988
TI  - Copper tolerance and response of antioxidative enzymes in axenically grown
      Brassica juncea (L.) plants.
AB  - Copper is an essential element for proper functioning of all living organisms
      including plants, but it can cause toxicity at elevated concentrations. In the
      present study, two varieties of Brassica juncea L. i.e. Pusa JK and TM 4 grown
      axenically were compared for Cu tolerance and accumulation ability. For further
      detailed biochemical studies, var. TM 4 was used because of its fast growth and
      better Cu accumulation in shoots. Toxic effects of Cu were manifested by a
      reduction in photosynthetic pigments and an increase in the levels of
      thiobarbituric acid reactive substances. The activities of antioxidant enzymes
      such as superoxide dismutase, ascorbate peroxidase, guaiacol peroxidase and
      catalase showed an increase in a concentration and exposure time dependent manner
      in roots of B. juncea exposed to copper, indicating that they play an important
      role in combating copper stress in this species.

PMID- 20825989
TI  - Effects of exposure water volume, depuration time, and feeding status on
      vitellogenin mRNA induction in male medaka (Oryzias latipes) exposed to 17 beta
      estradiol.
AB  - Bioassays measuring the induction of vitellogenin gene expression in male fish
      are widely used for revealing estrogenic activity in water samples. Measuring
      induction of vitellogenin mRNA in males by means of RT-PCR analysis is a
      sensitive way to detect exposure to estrogenic chemicals. To date, little work
      has been done to examine variations in exposure conditions for assessing
      estrogenic activity in water samples using this model system. Here we report the
      results of experiments investigating the effects of volume of treatment water,
      time since removal from treatment water (depuration), and short-term food
      deprivation on vitellogenin mRNA induction in male Japanese medaka (Oryzias
      latipes). Fish exposed to a single concentration of E(2) while volume was
      manipulated were found to have similar levels of vitellogenin mRNA, though more
      E(2) was present at larger volumes. Removal of fish from E(2)-treated-water to
      clean water after exposures reduced vitellogenin levels in as little 24h,
      however, the vitellogenin levels of the fish transferred to the clean water
      remained above those of the control fish for at least 72 h. Depriving fish of
      food for up to 72 h during exposure to E(2) did not significantly reduce
      vitellogenin induction. Together these results support the conclusion that real
      time RT-PCR measurement of vitellogenin in male fish can be used as a robust
      indicator of exposure to estrogenic contaminants in water.

PMID- 20825990
TI  - Effects of the fungicide azoxystrobin on Atlantic salmon (Salmo salar L.) smolt.
AB  - Atlantic salmon smolts were exposed to three doses of the fungicide azoxystrobin
      for 4 days, and physiological blood parameters and transcriptional effects in
      liver and muscle were evaluated in search for potential negative effects.
      Azoxystrobin exposure mediated up-regulation of catalase, MAPK1 and IGFBP1 in
      liver tissue. Catalase, transferrin, IGFBP1 and TNFR were up-regulated and CYP1A
      down-regulated in muscle tissue. Blood parameters glucose, hematocrit, pCO(2),
      HCO(3) and pH grouped together with transcripts levels of MnSOD, MAPK1, IGFBP1,
      MAP3K7 and GPx4 in liver of fish exposed to the highest azoxystrobin
      concentration (352 MUgL(-1)) using principal component analysis (PCA). In muscle,
      the blood parameters glucose, hematocrit, pCO(2), HCO(3) and pH grouped together
      with transcript levels of heme oxygenase, thioredoxin, MnSOD, TNFR and MMP9.
      These results suggest that the fungicide azoxystrobin affects mitochondrial
      respiration and mechanisms controlling cell growth and proliferation in fish and
      may have negative effects on juvenile Atlantic salmon.

PMID- 20825991
TI  - Morphologic effects of in vivo acute exposure to the pesticide methoprene on the
      hepatopancreas of a non-target organism, Homarus americanus.
AB  - Methoprene is a pesticide widely used for mosquito control. It is an endocrine
      disruptor, acting as an analog of juvenile hormone. While targeting insect
      larvae, it also impacts non-target animals including crustaceans. Anecdotal
      reports suggested that methoprene has unintended effects on adult arthropods.
      Earlier, we documented effects in adult lobsters at the metabolic and gene
      expression levels. In this study we have documented morphologic corollaries to
      our prior observations. We examined the light and electron microscopic changes in
      the hepatopancreas of adult lobsters following in vivo acute exposure to
      methoprene. Changes by light and electron microscopy levels were evident
      following exposure to sub-lethal concentrations of methoprene for 24h. Tissue
      from exposed animals showed the formation of extensive cytoplasmic spaces
      (vesiculation) with disruption and loss of specific subcellular organelles. The
      findings provide morphologic correlates to the metabolic and genomic alterations
      we have observed in previous investigations.

PMID- 20825992
TI  - Estimation of leaded (Pb) gasoline's continuing material and health impacts on 90
      US urbanized areas.
AB  - The subject of this paper is lead (Pb) additives in gasoline and their material
      and health impact from Pb dust inputs into 90 US urbanized areas (UAs). The mass
      of Pb additives for 90 UAs as a total of the US Pb additives in 1982 were
      estimated from vehicle travel, vehicle fuel economy (miles/gallon), ratio of
      leaded to unleaded fuel, and Pb/gallon. About 500 billion (109) miles of travel
      in 90 UA's during 1982 account for ~18,000 metric tons (MT), or nearly 30% of the
      US Pb additives in 1982. Applying the 1982 proportions to the 90 UAs for 1950
      through 1982 fuel sales by state accounts for ~1.4 million MT Pb of the US
      national total of 4.6 million MT during the same years. Fates of Pb additives in
      engine systems were used to calculate Pb aerosol inputs into the 90 UAs. The
      inputs range from 100's to more than 100,000 MT of Pb depending on a given UA's
      traffic flow patterns. Soils are the reservoir of urban Pb dust. The median
      background soil Pb for the US is 16.5mg/kg (range 10.3 to 30.1mg/kg), and less by
      an order of magnitude or more than soil Pb within larger UAs. Recognizing the US
      input of massive gasoline Pb additives into UAs assists with comprehending soil
      Pb differences between large and small UAs, inner and outer areas of UAs, health
      disparities, and school achievement issues within UAs. The findings underscore
      the need for controlling accumulated exterior urban Pb dust from gasoline
      additives along with paint sources that have accumulated in soil to meet the goal
      of primary childhood Pb exposure prevention.

PMID- 20825993
TI  - Genotoxicity of mercury: contributing for the analysis of Amazonian populations.
AB  - Mercury is an important source of environmental contamination affecting human
      beings throughout the world and especially in the Amazon. Riverside populations
      have been chronically exposed to relatively high levels of methylmercury for many
      years. Long-term effects of mercury exposure are not well known, but human
      genotoxicity was already showed in both in vitro and epidemiological studies.
      However, to date, only two studies were carried out in Amazonian populations with
      conflicting results and without comparing to a non-exposed population. Aiming to
      highlight this question and avoid interference factors, this work analyzed in
      vitro genotoxicity of mercury in blood lymphocytes of Amazonian individuals by
      two methods (micronucleus and chromosomal aberrations). Deleterious effects of
      low levels (1-500 MUg/l or 0,004-2 MUM) of methylmercury were only detected with
      the method to detect chromosomal aberrations. Mitotic index (proportion of cells
      in metaphase) was the parameter most sensible. Thus, this technique was applied
      for the analysis of an Amazonian non-exposed population (Panacauera) with similar
      social-economical characteristics of the exposed populations studied elsewhere.
      The mean of the mitotic index for Panacauera population was 0.0814 +/- 0.0097.
      Inter-individual variability of this index had no relation with sex or age. This
      value was above those registered for some groups of exposed populations. This
      fact points to mercury as the main responsible for inhibiting the cell cycle
      and/or the loss of proliferative capacity of the cells. These results already
      support mitotic index as an essential parameter for the early diagnose of mercury
      genotoxicity in humans, and especially in Amazonian populations.

PMID- 20825994
TI  - A caged nicotine with nanosecond range kinetics and visible light sensitivity.
AB  - We report the synthesis, characterization and applications of a ruthenium
      bipyridine based caged nicotine. The complex [Ru(bpy)(2)(nic)(2)](2+) (where bpy
      = 2,2' bipyridine and nic = nicotine (3-[(2S)-1-methylpyrrolidin-2-yl] pyridine))
      releases nicotine with a quantum yield phi = 0.23 upon irradiation with
      biologically harmless, blue (473 nm) or green (532 nm) light. The photolysis
      reaction is clean and very fast, with a time constant of 17 ns. The synthesis is
      simple and the obtained compound is characterized by NMR, UV-Vis spectroscopy and
      cyclic voltammetry. We find that this compound is active in biological systems,
      being able to elicit action potentials in leech neurons.

PMID- 20825995
TI  - Common basis for the mechanism of metallo and non-metallo KDO8P synthases.
AB  - The three-dimensional structures of metal and non-metal enzymes that catalyze the
      same reaction are often quite different, a clear indication of convergent
      evolution. However, there are interesting cases in which the same scaffold
      supports both a metal and a non-metal catalyzed reaction. One of these is 3-deoxy
      D-manno-octulosonate 8-phosphate (KDO8P) synthase (KDO8PS), a bacterial enzyme
      that catalyzes the synthesis of KDO8P and inorganic phosphate (P(i)) from
      phosphoenolpyruvate (PEP), arabinose 5-phosphate (A5P), and water. This reaction
      is one of the key steps in the biosynthesis of bacterial endotoxins. The
      evolutionary tree of KDO8PS is evenly divided between metal and non-metal forms,
      both having essentially identical structures. Mutagenesis and crystallographic
      studies suggest that one or two residues at most determine whether or not KDO8PS
      requires a metal for function, a clear example of "minimalist evolution". Quantum
      mechanical/molecular mechanical (QM/MM) simulations of both the enzymatic and non
      enzymatic synthesis of KDO8P have revealed the mechanism underlying the switch
      between metal and non-metal dependent catalysis. The principle emerging from
      these studies is that this conversion is possible in KDO8PS because the metal is
      not involved in an activation process, but primarily contributes to orienting
      properly the reactants to lower the activation energy, an action easily mimicked
      by amino acid side-chains.

PMID- 20825996
TI  - Utility of the Child Behavior Checklist in screening depressive disorders within
      clinical samples.
AB  - BACKGROUND: Previous studies analyzed the clinical validity of the Child Behavior
      Checklist (CBCL) for screening primary depressive disorders (major depression and
      dysthymia). Other psychiatric disorders with depressive symptomatology (e.g.
      adjustment disorders with depressive reaction) have not been a research focus to
      date. This study aims to examine the utility of the CBCL scales Anxious/Depressed
      and Affective Problems in screening both primary depressive disorders and other
      disorders with depressive symptomatology. METHODS: The two samples consisted of
      1445 outpatients and 698 inpatients aged 11-18 who were referred for child and
      adolescent psychiatric services. The predictive power of the CBCL scales was
      examined using ROC-analysis. RESULTS: Both CBCL scales showed small to medium
      predictive power when screening for primary and other depressive disorders in
      clinically referred outpatients (AUCs=.694-.780). Within the inpatient sample,
      only primary depressive disorders were detected with small predictive power
      different from chance level (AUCs=.625-.673). Both CBCL scales did not differ
      significantly with regards to predicting depressive disorders. LIMITATIONS: A
      limitation of this study is the lack of reliability checks for consensus
      classification process of the ICD-10 diagnoses. However, comparable prior work
      using structured interviews resulted in similar AUC values, supporting our
      findings. CONCLUSIONS: In outpatient samples, the CBCL is suitable for screening
      other depressive disorders in addition to primary depressive disorders. This is
      not the case for inpatients due to a misclassification number of 40%; thus using
      CBCL scales screen for depressive disorders in such populations warrants caution.

PMID- 20825997
TI  - Examining the role of emotion in suicidality: negative urgency as an amplifier of
      the relationship between components of the interpersonal-psychological theory of
      suicidal behavior and lifetime number of suicide attempts.
AB  - Joiner's (2005) interpersonal-psychological theory of suicidal behavior posits
      that an individual must exhibit elevations on three variables--perceived
      burdensomeness, thwarted belongingness, and the acquired capability for suicide-
      in order to enact lethal self-harm. Thus far, however, no research has examined
      the role of emotion in this process or whether the interaction of these three
      variables is more problematic for certain populations than for others. We sought
      to address these voids by examining the role of negative urgency as an amplifier
      of the relationship between the components of the theory and lifetime number of
      suicide attempts. Results indicated that the four-way interaction of negative
      urgency and the three components of the theory predicted lifetime number of
      suicide attempts, controlling for depression symptoms and sex. Additionally, the
      three-way interaction of the theory components significantly predicted lifetime
      number of suicide attempts in the full sample. Furthermore, for individuals with
      negative urgency scores at or above the median, the three-way interaction of the
      theory components significantly predicted lifetime number of suicide attempts
      whereas, for individuals with negative urgency scores below the median, the
      interaction was non-significant. These findings indicate that, although
      elevations on the three components of the theory may be dangerous for anyone,
      this is particularly true for individuals exhibiting high levels of negative
      urgency, as they might be more likely to quickly develop suicidal ideation and
      resort to painful self-harming behaviors while experiencing negative affective
      states.

PMID- 20825998
TI  - Obstetric and perinatal outcomes among women with blood- and injection phobia
      during pregnancy.
AB  - BACKGROUND: Little is known about how anxiety disorders affect pregnancy
      outcomes. Therefore we investigated the impact of one anxiety disorder, blood-
      and injection phobia, on obstetric and neonatal outcomes. METHODS: From a
      population-based prospectively collected cohort we compared an index group of 110
      women with blood- and injection phobia with a control group of 220 women.
      Standardized medical records were used to collect data. Obstetric and neonatal
      outcomes e.g. elective cesarean, prematurity, and small for gestational age were
      used as the main outcome measures. RESULTS: Women with blood- and injection
      phobia stated more often a fear of childbirth (p<0.001) and were more frequently
      delivered by elective cesarean section (p=0.032). The incidence of premature
      delivery (p=0.028), neonatal morbidity (p=0.001) and the risk of having a baby
      born small for gestational age (p=0.009) was higher among women with blood- and
      injection phobia. LIMITATIONS: The medical records, from which all information is
      drawn, despite standardization, sometimes may lack some information. However,
      this dilemma exists in both groups. CONCLUSIONS: Women with an anxiety disorder
      such as blood- and injection phobia are at increased risk for adverse obstetric
      outcomes, premature delivery and for having a baby born with higher neonatal
      morbidity. It therefore seems important to identify and treat women with anxiety
      disorders without delay early during pregnancy in an effort to minimize risks of
      complications for the woman herself and the child.

PMID- 20825999
TI  - Familial influence of substance use disorder on emotional disorder across three
      generations.
AB  - The concomitant influence of grandparental (Generation 1; G1) and parental (G2)
      substance use disorder (SUD) on grandchild (G3) emotional disorder (EmD) across
      three generations is unclear. The present study addressed this in a sample of 284
      families participating in the Oregon Adolescent Depression Project. Structured
      clinical interviews were used to collect psychiatric history data on a community
      cohort of G2 individuals and their G1 parents. G2 parents rated EmD symptoms in
      their G3 children (M age=5 years, SD=2.4). Results indicated that G1 SUD was
      associated with increased risk of G3 EmD symptom elevations, above and beyond the
      influence of comorbid G1 EmD. G2 SUD was associated with a similar independent
      increase in risk for G3 EmD symptoms. Also, G1 SUD conferred risk for G2 SUD.
      Mediational tests indicated that the influence of G1 SUD on G3 EmD was
      transmitted via its influence on G2 SUD. G1 and G2 SUD did not interact in
      predicting G3 EmD; rather results suggested an additive influence. There was no
      evidence that the influence of G1 SUD on G3 EmD was transmitted via G2 EmD. These
      findings shed light on the multigenerational processes through which SUD
      influences EmD.

PMID- 20826000
TI  - Exploring the affective component of pain perception during aversive stimulation
      in borderline personality disorder.
AB  - In a pilot study, affective components of pain were assessed using repetitive
      peripheral magnetic stimulation (rPMS) in patients with borderline personality
      disorder and healthy controls. Significant differences in pain thresholds and in
      affective components of pain between both groups were found. rPMS was well
      tolerated and suitable for assessing pain.

PMID- 20826001
TI  - Altered sense of agency in schizophrenia and the putative psychotic prodrome.
AB  - The mechanisms underlying distortions in sense of agency, i.e. the experience of
      controlling one's own actions and their consequences, in schizophrenia are not
      fully understood and have barely been investigated in patients classified as
      being in a putative psychotic prodrome. This study aims to expound the
      contribution of early and late illness-related processes. Thirty schizophrenia
      patients, 30 putatively prodromal patients and 30 healthy controls were
      instructed to reproduce a computer-generated series of drum sounds on a drum pad.
      While tapping, subjects heard either their self-produced tones or a computer
      controlled reproduction of the drum tone series that used either exactly the
      same, an accelerated or decelerated tempo. Subjects had to determine the source
      of agency. Results show similar significant impairments in assigning the source
      of agency under ambiguous conditions in schizophrenia and putatively prodromal
      patients and an exaggerated self-attribution bias, both of which were
      significantly correlated with increased (ego-)psychopathology. Patient groups,
      however, benefited significantly more than controls from additional sensorimotor
      cues to agency. Sensorimotor input seems to be a compensatory mechanism involved
      in correctly attributing agency. We deduce that altered awareness of agency may
      hold promise as an additional risk factor for psychosis.

PMID- 20826002
TI  - Criminal recidivism in offenders with personality disorders and substance use
      disorders over 8 years of time at risk.
AB  - Personality disorders (PD) and substance use disorders (SUD) lead to high violent
      criminality. The influence of co-morbidity on recidivism remains unclear.
      Recidivism of 379 offenders was assessed at 8 years of follow-up. Sixty-nine
      percent of PD+SUD, 45% of SUD- and 33% of PD- subjects showed any recidivism.
      However, violent recidivism was highest in the PD- group.

PMID- 20826003
TI  - Gender differences in outcome of eating disorders: a retrospective cohort study.
AB  - Eating disorders (EDs) are uncommon in males. The majority of outcome studies on
      ED have not presented gender-specific results, mostly because of small study
      samples or exclusion of males. Furthermore, psychometric tools and outcome
      criteria used in ED have mainly been validated for females only. The objective of
      this study was to evaluate gender differences in weight restoration in different
      EDs. We studied the male representation and outcome in a large retrospective
      single centre cohort, the Funen Anorexia Nervosa Study (FANS). A total of 1015
      patients were included in the study. A total of 356 (35%) patients were diagnosed
      with anorexia nervosa (AN), 298 (29%) with eating disorder not otherwise
      specified (EDNOS) and 361 (36%) with bulimia nervosa (BN). The male fractions in
      AN and EDNOS were similar, but significantly lower in BN. When remission was
      defined as body weight restoration to at least 85% of ideal body weight (IBW) and
      no self-reported binge or purgative behaviors in six months, the median time from
      onset to remission for patients with AN was significantly shorter for males: 7
      years for females vs. 3 years for males. Among patients with a 5 years history of
      disease, remission rates in AN were 39% for females vs. 59% for males. The median
      time to remission for patients with EDNOS was similar to that of AN: 6 years for
      females vs. 3 years for males. In patients with EDNOS, 45% of the females
      remitted within 5 years vs. 77% of the males. With regard to body weight
      restoration and remission of purging behavior, this study suggests a better
      outcome for males than for females.

PMID- 20826004
TI  - Eye tracking performance and the boundaries of the schizophrenia spectrum.
AB  - In order to investigate the nature of the eye tracking impairment in
      schizophrenia spectrum we measured pursuit gain with a constant velocity target
      using a quantitative (RMS error in pursuit gain) and, on an exploratory basis, a
      qualitative (quality of tracking) measure. We utilized a sample consisting of
      three clinically characterized groups: patients with schizophrenia (SZ), their
      first degree non-psychotic relatives, subjects with schizotypal personality
      disorder (SPD), and healthy volunteers (HV). Thirty three SZ patients, 19 SPD
      subjects, 66 non-psychotic relatives (all clinically assessed for schizophrenia
      spectrum psychopathology--DSM-IIIR) and 18 HV were evaluated using an infrared
      eye tracking system. Targets were constant velocity trapezoids at 5 degrees /s
      (slow) and 16 degrees /s (fast). The quality of the eye tracking was
      independently evaluated by at least two raters (ICC: 0.92). The RMS measures at
      the two velocities (quantitative measure) and the quality of the tracking
      obtained for each velocity were entered separately into a two factor repeated
      measures ANOVA, with velocity and diagnosis as the independent measures. For the
      quantitative ratings (RMS error), a significant effect for velocity was found,
      with all subjects performing worse at the higher velocity, but there was no
      significant velocity by diagnosis interaction. In addition, an overall
      significant effect for diagnosis was found in the four-group ANOVA. In post hoc
      multiple comparison tests, SZ subjects performed significantly worse from the HV
      and the relatives. SPD subjects were not different from patients with
      schizophrenia (or from any group--and their performance was intermediate between
      the HV and the SZ). Relatives of the patients with schizophrenia were different
      from SZ subjects, but not different from SPD or HV subjects. Similar results were
      obtained in the exploratory qualitative ratings. Clinical symptoms did not
      correlate significantly with quantitative or qualitative performance in any
      group. We have found that the performance of SPD subjects is intermediate between
      that of patients with schizophrenia and the healthy volunteers in both
      qualitative and quantitative (exploratory) measures. Indeed, SPD subjects
      comprise the only group not statistically different from schizophrenic patients
      in quantitative or qualitative ratings.

PMID- 20826005
TI  - Night eating patterns of individuals with eating disorders: implications for
      conceptualizing the night eating syndrome.
AB  - The prevalence, correlates, and symptom coherence of night eating syndrome (NES)
      in individuals seeking inpatient treatment for eating disorders were assessed.
      Inpatients (n=68; M age=29.8 years; % female=94.1; % diagnosed with anorexia
      nervosa [AN]=47.1; % diagnosed with bulimia nervosa [BN]=47.1) were interviewed
      with the Night Eating Syndrome History and Inventory. Additionally, medical
      charts were reviewed and participants completed measures of eating behavior and
      quality of life. NES was diagnosed in 25% of patients; significantly more
      patients diagnosed with BN meet criteria for NES compared to those diagnosed with
      AN. In general, patients with NES did not differ from patients without NES on
      eating behaviors, attitudes, or quality of life; symptoms of NES frequently co
      occurred. This study supports previous research finding that night eating
      behavior is common in individuals diagnosed with eating disorders.

PMID- 20826006
TI  - Diurnal variation and gender differences of plasma brain-derived neurotrophic
      factor in healthy human subjects.
AB  - Diurnal changes of brain-derived neurotrophic factor (BDNF) mRNA and protein
      contents have been demonstrated in the rat central nervous system. In humans,
      however, insufficient data are available on diurnal variation of BDNF. We
      investigated plasma and serum BDNF levels at three different times of the day (9
      a.m., 1 p.m. and 5 p.m.) in 18 healthy men and 18 healthy women. BDNF levels were
      assessed using an enzyme-linked immunosorbent assay (ELISA). We detected
      significant diurnal variation in plasma BDNF level in men, with a constant
      decrease throughout the day. However, we could not find diurnal variation in
      either the plasma BDNF of women or the serum BDNF in both men and women. When
      performing analysis of covariance with the age and body mass index as covariates,
      we found no significant differences of plasma and serum BDNF levels of the two
      sexes at the three time points. In psychiatric studies of blood BDNF level,
      diurnal variation in plasma BDNF level should be considered with respect to
      gender differences.

PMID- 20826008
TI  - Epstein-Barr virus infection of human brain microvessel endothelial cells: a
      novel role in multiple sclerosis.
AB  - Multiple sclerosis (MS) is an inflammatory neurological disease that is widely
      regarded as the outcome of complex interactions between a genetic predisposition
      and an environmental trigger. Epstein-Barr virus (EBV) has recently been
      associated with the onset of MS, yet understanding how it elicits autoimmunity
      remains elusive. Neuroinflammation, including the entry of autoreactive T cells,
      likely follows a breach of the blood-brain barrier (BBB) leading to CNS lesions
      in MS. We show that EBV can infect human BBB cells leading to increased
      production of pro-inflammatory mediators that result in immune cell adherence
      thus modeling a key step in MS pathogenesis.

PMID- 20826007
TI  - Differential responses of human microglia and blood-derived myeloid cells to
      FTY720.
AB  - Human microglia, monocyte-derived dendritic cells (DCs) and macrophages ex vivo
      express relatively higher levels of sphingosine-1-phosphate (S1P) receptor 1
      (S1P1) mRNA as compared to other receptor subtypes. The S1P agonist FTY720
      decreased ERK phosphorylation and induced myosin light chain (MLC) II
      phosphorylation only in macrophages and DCs. FTY720 inhibited IL-12p70 production
      (CD40L induced) by DCs and macrophages but not microglia (poly I:C induced). IL
      10 production was increased in DCs and unaffected in other myeloid cells. Despite
      similar receptor expression patterns, the distinct myeloid cell populations
      present in the human CNS, under steady-state or inflammatory conditions, exhibit
      differential responses to FTY720.

PMID- 20826009
TI  - KIRs and their HLA ligands in remitting-relapsing multiple sclerosis.
AB  - Killer Immunoglobulin-like Receptor (KIR) genes may affect both resistance and
      susceptibility to autoimmune disorders, but their role in the pathogenesis of
      Multiple Sclerosis (MS) is still unclear. To evaluate the involvement of KIRs and
      their HLA ligands in the development of MS we performed genotyping of HLA -A, -B,
      -Cw, -DRB1 and KIRs loci in 121 RRMS patients and 103 healthy controls (HC).
      Results evidenced a possible protective role of the activating KIR2DS1 gene
      (p(y)=0.001; OR:0.38), enhanced in the presence of its ligand group HLA-C2
      (p(y)=0.0001; OR:0.23). Our data suggest that the presence of functional
      compounds of activating KIR receptors together with their HLA ligands, allowing
      the immunomodulatory function of NK cells, may have a protective role against the
      disease.

PMID- 20826010
TI  - Epstein-Barr virus and multiple sclerosis: cellular immune response and cross
      reactivity.
AB  - We investigated T cell immunity to Epstein-Barr virus (EBV) in multiple sclerosis
      (MS) and assessed cross-reactivity of the anti-EBV cellular response with brain
      antigens. We measured the proliferation, cytotoxicity, and number of interferon
      gamma secreting cells following stimulation with autologous EBV-infected
      lymphoblastoid cell lines (LCL) in MS patients and matched controls. There were
      no statistically significant differences for any of the measured responses, but
      there was a trend towards decreased proliferative responses in MS patients. There
      was no measured cross-reactivity between LCL and brain antigens. We conclude that
      the cellular immune response against EBV-infected cells is neither increased nor
      decreased in MS.

PMID- 20826011
TI  - T cells that trigger acute experimental autoimmune encephalomyelitis also mediate
      subsequent disease relapses and predominantly produce IL-17.
AB  - Earlier studies showed that donor T cells that initiated a murine adoptive EAE
      persisted in the CNS of the recipients throughout the subsequent relapsing
      cycles. To clarify the functions of the persistent donor T cells in EAE relapsing
      disease, anti-Thy-1 antibodies were used to deplete these cells. Results showed
      that such treatment abrogated subsequent relapsing cycles in these animals. In
      addition, it was evident that a shift in cytokine profile occurred during acute
      and relapsing disease phases. These results unambiguously support the
      appropriateness of targeting T cells with specificity for the priming antigen in
      design of therapeutic approaches for MS.

PMID- 20826012
TI  - Inflammatory cytokine release of astrocytes in vitro is reduced by all-trans
      retinoic acid.
AB  - In the central nervous system inflammation is mediated by microglia and
      astrocytes. To investigate its regulation, murine astrocyte cultures were treated
      with bacterial lipopolysaccharides (LPS) and analyzed with Affymetrix gene array,
      qRT-PCR and ELISA. Cells responded to LPS with a strong upregulation of pro
      inflammatory cytokines and chemokines. Treatment with the transcriptional
      activator retinoic acid (RA) suppressed mRNA expression and protein release of
      several important cytokines (IL-1beta 4%, IL-6 21%, TNFalpha 30%, IL-12p40 42%,
      and IL-12p35/p40 27%; p<0.01). The data are consistent with the hypothesis that
      all-trans RA takes part in endogenous anti-inflammatory feedback loops in the
      CNS.

PMID- 20826013
TI  - Intrauterine infection/inflammation and perinatal brain damage: role of glial
      cells and Toll-like receptor signaling.
AB  - The mechanisms or pathophysiology that leads to preterm brain damage including
      white matter damage during development are complex and not fully understood.
      Intrauterine infection/inflammation can significantly affect perinatal brain
      development and result in significant alterations in brain structure and
      function. Glial cells and Toll-like receptors (TLRs) are vital players in central
      nervous system immune response; dysregulation of this response plays an important
      role in brain damage. Intrauterine infection/inflammation has immunomodulatory
      effects and induces specific alterations in the TLRs response in many tissues.
      Recent findings indicate that intrauterine infection/inflammation could promote
      inflammatory processes in brain and in glial cells by up-regulating cytokines and
      inflammatory mediators, and by activating signaling pathways and transcriptional
      factors (nuclear factor-kappaB) implicated in inflammatory injury. TLRs may be
      involved in intrauterine infection-mediated inflammatory signaling, and
      intrauterine infection/inflammation could interfere with the TLR4 recruitment
      into the lipid rafts, leading to an effect on the TLR signaling transduction. In
      summary, current results suggest that TLRs are key mediators of intrauterine
      infection/inflammation induced preterm brain damage.

PMID- 20826014
TI  - Quantitative evaluation of left atrial volumes and ejection fraction by 320-slice
      computed-tomography in comparison with three- and two-dimensional
      echocardiography: a single-center retrospective-study in 22 subjects.
AB  - PURPOSE: To evaluate efficacy and reproducibility of 320-slice computed
      tomography (CT) for measuring left atrial (LA) maximum (LAVmax) and minimum
      volume (LAVmin) during the cardiac cycle, we compared CT with three- and two
      dimensional (3D and 2D) transthoracic echocardiogram (TTE). MATERIALS AND
      METHODS: LAVmax and LAVmin (ml), and LA ejection fraction (LAEF) (%) were
      assessed in 22 consecutive subjects (15 males, 59.5 +/- 15.1 years) using
      retrospective electrocardiogram gated 320-slice CT (Aquilion One, Toshiba
      Medical) and 3D-TTE (IE-33, Phillips). LAVmax and LAVmin were selected from the
      time volume curve. LAEF was calculated as (LAVmax-LAVmin)/LAVmax*100(%). RESULTS:
      Mean +/- standard deviation (SD) of LAVmax and LAV min were significantly larger
      by CT than 3D-TTE or 2D-TTE (both P<0.01). LAEF was 25.3 +/- 13.1% by CT, 30.2 +/
      6.8% by 3D-TTE (P=NS) and 33.9 +/- 8.9% by 2D-TTE (P<0.05). The correlation
      coefficients (CCs) between CT and 3D-TTE in LAVmax, LAmin, and LAEF were 0.64,
      0.68 and 0.57, respectively. Mean difference +/- 1.96SD of LAVmax, LAVmin and
      LAEF by Bland and Altman analysis calculated from CT minus 3D-TTE were 48.8 +/-
      59.1 ml, 41.1 +/- 63.2 ml, and -4.9 +/- 21.1%, respectively. The CCs and mean
      difference +/- 1.96SD between CT and 2D-TTE had similar tendencies. The CCs of
      interobserver variation were (for CT, 3D-TTE, 2D-TTE, respectively): 0.90, 0.95
      and 0.94 (LAVmax), 0.97 and 0.97 and 0.93 (LAVmin), and 0.64, 0.77 and 0.34
      (LAEF). CONCLUSIONS: 320-slice CT enables direct LAV measurements and has high
      reproducibility and positive correlation with 3D and 2D TTE. Absolute value of
      LAV by CT was larger than that by 3D and 2D TTE.

PMID- 20826015
TI  - Clinical cardiac involvement in idiopathic inflammatory myopathies: a systematic
      review.
AB  - BACKGROUND: Idiopathic inflammatory myopathies (IIM) presenting with diffuse
      skeletal muscular inflammation and cardiac involvement is one of the major causes
      of clinical deterioration. Our purpose was to observe the frequency of various
      reported clinical cardiac afflictions, cardiovascular mortality and its most
      important contributors in the IIM population. METHODS: MEDLINE database was
      searched from 1977 through 2009. Articles reporting objective evidence of cardiac
      involvement were assessed. Patients were included if they satisfied Bohan and
      Peter criteria for definite or probable diagnosis of IIM. The review conforms to
      the criteria of the new PRISMA statement of preferred reporting items for
      systematic reviews and meta-analyses. RESULTS: Thirty-three out of 90 articles
      reported cardiac data. Twelve were case reports, while 21 articles were either
      cohort studies or case series. Angina was reported in 7% of cumulative
      prospective cohort. Dysrhythmias were seen in 31.8% of electrocardiograms.
      Diastolic dysfunction was the most common echocardiographic finding. Congestive
      heart failure was reported in 5.6% of the prospective cohort and was the most
      common cause of death accounting for 21% of total cardiac mortality. Myocarditis
      was the most common feature in reported pathology literature (38%), followed by
      focal myocardial fibrosis (22%). CONCLUSION: Cardiac involvement is an important
      cause of morbidity and mortality in patients with IIM. Myocardial fibrosis puts
      the patient at risk for systolic or diastolic heart failure and dysrhythmias.
      This review, therefore, suggests the importance of early and comprehensive
      cardiac evaluation in IIM population. Confirmation of these findings will require
      prospective studies of consecutive patients with long-term follow-up.

PMID- 20826016
TI  - Unending debate: statin dilemma in the management of heart failure.

PMID- 20826017
TI  - High-risk PCI in acute coronary syndromes with Impella LP 2.5 device support.
AB  - OBJECTIVES: To evaluate feasibility, safety, efficacy as well as acute and short
      term outcome of hemodynamically supported percutaneous coronary intervention
      (PCI) by a percutaneous, catheter-based left ventricular assist device (LVAD)
      (Impella LP 2.5, Abiomed Europe GmbH, Aachen, Germany) in a high-risk patient
      population with acute coronary syndrome. BACKGROUND: Although hemodynamic support
      by intraaortic balloon pump favorably affects myocardial oxygen supply and
      demand, it has modest effects on cardiac output, providing passive support only.
      In contrast, the Impella LP 2.5 microaxial pump, which is placed within the left
      ventricular outflow tract and actively ejects blood into the ascending aorta,
      might offer additional hemodynamic support and thereby procedural safety during
      PCI. METHODS: Thirty-eight consecutive high-risk patients (mean age, 69.7 +/-
      10.3 years, logistic EuroSCORE, 22.4 +/- 14.9%) with unstable angina pectoris or
      non-ST-segment elevation myocardial infarction and severe three-vessel-disease
      were included in the study. Clinical and laboratory examinations were performed
      at baseline as well as at 6, 24 and 48 h after the procedure and 30 days after
      discharge. RESULTS: Device insertion and explantation was feasible in all
      patients without vascular complications and continuous hemodynamic stability was
      obtained during PCI. PCI was uneventfully performed in all but one patient for
      technical reasons. One non procedure-related death occurred 7 days after the
      intervention, accounting for a total 30-day mortality of 2.86%. Other major
      cardiac or cerebrovascular events did not occur. CONCLUSIONS: LVAD support using
      a percutaneous microaxial flow pump is a promising and safe approach for high
      risk PCI providing good short-term results.

PMID- 20826018
TI  - New-onset diabetes and cardiovascular events in essential hypertensives: a 6-year
      follow-up study.
AB  - BACKGROUND: Controversy still exists regarding the impact of new-onset diabetes
      (NOD) on CV outcomes among patients with hypertension. Our aim was to determine
      the incidence of NOD in essential hypertensives and to evaluate its association
      with major cardiovascular (CV) events. METHODS: We followed-up for a mean period
      of 6 years 1572 essential hypertensives (mean age 54.3 years, 696 males) for the
      incidence of NOD, as well as of fatal and non-fatal coronary artery disease and
      stroke. Based on the development of NOD, the cohort was divided into patients
      with pre-existing diabetes (10%), patients with NOD (10%) and those who remained
      free from diabetes. RESULTS: During the follow-up period, new or recurrent cases
      of coronary artery disease and stroke events occurred at a rate of 5.6% (n = 88)
      and 4.65% (n = 73). The independent predictors for NOD were age (OR = 1.026, p =
      0.041), waist circumference (OR = 1.044, p < 0.001), family history of diabetes
      (OR = 2.173, p = 0.003) and systolic BP at follow-up (OR 1.022, p = 0.044). The
      presence of NOD was independently associated with greater incidence of stroke (HR
      2.404, p = 0.046), along with age (HR 1.078, p < 0.001), duration of hypertension
      (HR 1.039, p = 0.017) and office systolic blood pressure at follow-up (HR 1.022,
      p = 0.026), whereas development of NOD had no relationship with the incidence of
      coronary artery disease. CONCLUSIONS: Our findings indicate the high incidence of
      NOD and its close association with stroke in essential hypertension. Poorer
      control of hypertension appears to be a common denominator of both NOD and stroke
      in this setting.

PMID- 20826019
TI  - The use of an automated patient registry to manage and monitor cardiovascular
      conditions and related outcomes in a large health organization.
AB  - BACKGROUND: The present study describes a computerized registry of cardiovascular
      disease patients in a large health maintenance organization in Israel. The
      registry is aimed to be used by health professionals to identify cardiovascular
      disease patients and to follow the courses of their illnesses and risk factors.
      METHODS: In 1998, the registry was initiated using advanced information
      technology that integrated personal computerized community and hospital records,
      data from laboratory tests, dispensed medications, physiological signals,
      radiological images, and reports from investigations and procedures. RESULTS:
      Between 1998 and 2007, the number of patients with cardiovascular diseases that
      were identified by the registry has increased from 34,144 to 80,339. During this
      period, the age-adjusted prevalence rates have risen from 3.7% to 5.1% and from
      1.9% to 2.6%, among men and women, respectively. The percentage of ischemic heart
      disease patients who reached target LDL was doubled, from 21% in 2000 to 50% in
      2006. The average stay in hospital declined from 11.7 to 8.6 days. Primary
      myocardial infarction rates declined 33% and 54% in men aged 54-65 and women aged
      65-74 years, respectively. CONCLUSIONS: The present study provides, for the first
      time in Israel, data on selected quality of care and clinical outcomes using a
      large, population-based registry of cardiovascular disease patients. It
      demonstrates a significant improvement in the adherence with LDL tests and
      achieving target LDL levels and a subsequent decline in incidence of myocardial
      infarction within ten years since its establishment.

PMID- 20826020
TI  - Rapid cardiac hybrid imaging with minimized radiation dose for accurate non
      invasive assessment of ischemic coronary artery disease.
AB  - BACKGROUND: Ischemic coronary artery disease (CAD) is a major cause for morbidity
      and mortality resulting in a continuously increasing number of diagnostic
      interventions. We have validated a new hybrid imaging method using minimized
      radiation dose for rapid non-invasive prediction of invasive coronary angiography
      (CA) findings with regard to coronary lesion detection and revascularization.
      METHODS: Forty patients referred for elective invasive coronary angiography (CA)
      due to suspected CAD were prospectively enrolled to undergo a low-dose CTCA with
      prospective ECG-triggering and a stress-only SPECT-MPI scan administering half of
      the standard low-dose stress (99m)Tc-tetrofosmin activity. The latter was
      acquired immediately after adenosine stress (omitting the standard 30-60 min
      waiting time). After fusing CTCA and SPECT-MPI decisions towards conservative
      management versus revascularization strategy based on hybrid images were compared
      to the decisions taken by the interventional operator in the catheterization
      laboratory based on CA. The latter served as standard of reference. RESULTS:
      Hybrid images yielded sensitivity, specificity, positive and negative predictive
      values and accuracy of 100%, 96.0%, 100%, 93.8% and 97.5% for predicting coronary
      revascularization. The estimated mean effective radiation doses were
      significantly lower for hybrid imaging (4.7 +/- 1.0 mSv) than for invasive CA
      (8.7 +/- 4.2 mSv; P<0.001 vs. hybrid). Total non-invasive protocol time was below
      60 min, comparing favourably to standard SPECT protocols. CONCLUSIONS: Rapid
      cardiac hybrid imaging allows accurate prediction of invasive CA findings and of
      treatment decision despite minimized radiation dose and protocol time.

PMID- 20826021
TI  - Patients with premature cardiovascular disease and a positive family history for
      cardiovascular disease are prone to recurrent events.
AB  - BACKGROUND: Premature cardiovascular disease (CVD) is treated in the same way as
      CVD of advanced age. However, in patients with premature CVD and a family history
      of CVD, different -possibly genetic- mechanisms may underlie this disease, which
      current medical treatment is not targeted to. This suggests that subjects with a
      genetic predisposition to CVD are more likely to have recurrent cardiovascular
      events. METHODS: We retrospectively investigated 291 patients with premature CVD
      and assessed the amount of recurrent events according to family history in a
      follow-up period of 31 years. Premature CVD was defined as an event <51 years for
      men or <56 for women. We used a Cox proportional hazards model to estimate the
      relationship between a positive family history and recurrence of cardiovascular
      events. RESULTS: Patients with recurrent events had more often a positive family
      history (60.0% vs. 47.1%; p<0.05), were more often smokers (85.2% vs. 70.7%;
      p<0.05), had more often hypertension (36.3% vs. 23.6%; p<0.05) and had a longer
      follow-up period (10.0 years vs. 5.4 years; p<0.001) than patients without
      recurrent events. After adjusting for these differences and modelling time to
      events, a positive family history was independently associated with recurrent
      events (Hazard ratio 1.31 (95% confidence intervals (CI) 1.01-1.72; p<0.05)).
      CONCLUSIONS: Patients with a genetic predisposition for CVD are at risk for
      recurrent events, after adjusting for risk factors and other confounders. This
      might imply that in subjects with a genetic predisposition for CVD different
      pathophysiological mechanisms are active, leading to recurrent events.

PMID- 20826022
TI  - Familial hypercholesterolemia and triglyceride metabolism.
AB  - Familial hypercholesterolemia (FH) is a common autosomal disorder associated with
      hypercholesterolemia which usually results from a mutation in the coding region
      of the low density lipoprotein (LDL) receptor (R) activity. Only 20% of untreated
      heterozygote (h) FH men reach 70 years of age. Therefore, the diagnosis of hFH is
      a better predictor of coronary heart disease than risk-based algorithms. Fasting
      and postprandial hypertriglyceridemia are also considered as risk factors for
      atherosclerosis. The plasma triglycerides (TG)s are formed from two major
      sources; intestinally-derived chylomicrons and hepatically-derived very low
      density lipoproteins (VLDL). Potentially, atherogenic remnants of TG-rich
      lipoproteins accumulate in the postprandial state. In addition, TG-rich
      lipoproteins may promote the formation of atherogenic small dense LDL. In FH
      subjects, lipoprotein metabolism seems to be impaired and may contribute to
      premature atherosclerosis. This was documented in many studies in which mice
      lacking LDLR present hypercholesterolemia, increased plasma TG-rich lipoprotein
      remnants and develop premature spontaneous atherosclerosis. In this review, we
      focus on the current knowledge regarding TG metabolism on a selected clinically
      condition such as FH. Variation in clinical characteristics has been described
      between studies which may occur due to dissimilarity in the molecular defect of
      FH. Additionally, the relationship between TG levels in FH subjects and the
      development of atherosclerosis, as well as the appropriate treatment for these
      patients is analysed.

PMID- 20826023
TI  - Differentiation of pseudodyskinesis of inferior left ventricular wall from
      inferior myocardial infarction by assessment of regional myocardial strain using
      two-dimensional speckle tracking echocardiography.
AB  - PURPOSE: To differentiate pseudodyskinesis (PD) of the inferior left ventricular
      (LV) wall from inferior myocardial infarction (IMI) noninvasively, we performed
      focal site evaluation using two-dimensional speckle tracking transthoracic
      echocardiography (TTE). MATERIALS AND METHODS: Speckle tracking TTE was carried
      out in 57 patients, with 19 subjects in each of three groups (Group A, suspected
      PD; Group B, LV IMI; and Group C, controls). Inferior wall PD was defined as
      follows: compression of the inferior LV wall by the diaphragm in the LV short
      axis view with a normal electrocardiogram and no evidence of previous ischemic
      events. RESULTS: Respective values in Groups A-C for LV ejection fraction (EF)
      were 63.6 +/- 4.2%, 52.3 +/- 7.6%, and 61.5 +/- 3.8%, for inferior wall speckle
      tracking focal site evaluation peak radial strain of 30.0 +/- 14.3%, 7.5 +/-
      7.1%, and 42.1 +/- 22.9%, for peak circumferential strain of 23.1 +/- 6.0%, 16.8
      +/- 8.4%, and 22.7 +/- 7.1%, and for longitudinal strain in the mid-inferior wall
      of 18.4 +/- 3.4%, 11.4 +/- 4.0% and 15.8 +/- 5.9%. LVEF values were significantly
      lower in Group B than Groups A and C (P<0.001), as were those of radial,
      circumferential, and longitudinal strains (P<0.05). In receiver-operating
      characteristic analysis the optimal cut-off values with corresponding
      sensitivities and specificities for differentiation of PD from IMI were >19% with
      84.2% and 94.7% for radial, >15% with 89.4% and 52.6% for circumferential, and
      >15% with 73.6% and 100% for longitudinal strain, respectively. CONCLUSIONS:
      Determination of regional strain from speckle tracking TTE, especially radial and
      longitudinal strains, can provide focal and quantitative noninvasive evaluation
      for distinguishing PD of the inferior wall from IMI.

PMID- 20826024
TI  - Achieving coordinated secondary prevention of coronary heart disease for all in
      need (SPAN).
AB  - Effective disease management after an acute coronary event is essential, but
      infrequently implemented, due to challenges around the research evidence and its
      translation. Policy-makers, health professionals and researchers are confronted
      by the need for increased services, to improve access and equity, but often with
      finite and reducing resources. There is a clear need to develop innovative ways
      of delivering ongoing preventative care to the vast and increasing population
      with coronary disease. However, translation into clinical practice is becoming
      increasingly difficult while the volume of trial and review evidence of disparate
      models of delivery expands. Indeed, the prevention literature has evolved into a
      complex web of differing models offered to diverse patient populations in an
      array of settings. We describe a united organisation of care that aims to
      facilitate coordinated secondary prevention for all in need (SPAN). SPAN is
      inherently flexible yet provides a minimum level of health service
      standardisation. It can be delivered across any area health service regardless of
      a patient's age, gender, ethnicity, geographical location, or socioeconomic
      status. Importantly, the setting, communication technologies and components of
      each patient's care are governed and woven into continuing care provided by the
      family physician in concert with a cardiac care facilitator.

PMID- 20826025
TI  - Local persistent hypercoagulability after sirolimus-eluting stent implantation in
      patients with stable angina.
AB  - BACKGROUND: Late stent thrombosis (LST) after sirolimus-eluting stent (SES)
      implantation has been demonstrated previously. Although incomplete neointimal
      coverage after SES implantation has been reported, local long-term
      hypercoagulability remains unknown. METHODS: We evaluated the local persistent
      coagulative response in eighty-three consecutive patients with stable angina,
      treated with either SES (n=51) or BMS (n=32) implantation for isolated de novo
      left anterior descending (LAD) stenosis. We measured prothrombin fragment F1+2
      (frF1+2) and D-dimer levels sampled in the coronary sinus (CS) and sinus of
      Valsalva (V). The transcardiac gradient (Delta) was defined as the CS level minus
      V level. RESULTS: The DeltafrF1 + 2 and DeltaD-dimer were significantly greater
      in the SES group than in the BMS group (0.50 +/- 0.35 vs -0.14 +/- 0.15 nmol/l,
      p=0.009 and 0.24 +/- 0.21 vs -0.05 +/- 0.16 MUg/ml, p=0.041, respectively). We
      selected the hypocoagulative [DeltafrF1 + 2<0.15 (mean value-SD) nmol/l, n=21]
      and hypercoagulative [DeltafrF1 + 2>0.85 (mean value+SD) nmol/l, n=14] groups out
      of the SES patients. Multivariate analysis was performed to identify independent
      predictors of local hypercoagulability. Total SES length was the only independent
      predictor of local hypercoagulability. There was a significant positive
      correlation between the DeltafrF1 + 2 and total stent length in the SES group
      (r=0.57, p<0.05). CONCLUSIONS: An increased local coagulative response was
      observed in the convalescent phase after SES implantation as compared to BMS.
      Careful long-term follow-up of patients after longer SES implantation is
      recommended in order to avoid LST.

PMID- 20826026
TI  - Precise correlation between MRI and histopathology - exploring treatment margins
      for MRI-guided localized breast cancer therapy.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is more often considered to guide,
      evaluate or select patients for partial breast irradiation (PBI) or minimally
      invasive therapy. Safe treatment margins around the MRI-visible lesion (MRI-GTV)
      are needed to account for surrounding subclinical occult disease. PURPOSE: To
      precisely compare MRI findings with histopathology, and to obtain detailed
      knowledge about type, rate, quantity and distance of occult disease around the
      MRI-GTV. METHODS AND MATERIALS: Patients undergoing MRI and breast-conserving
      therapy were prospectively included. The wide local excision specimens were
      subjected to detailed microscopic examination. The size of the invasive (index)
      tumor was compared with the MRI-GTV. The gross tumor volume (GTV) was defined as
      the pre-treatment visible lesion. Subclinical tumor foci were reconstructed at
      various distances to the MRI-GTV. RESULTS: Sixty-two patients (64 breasts) were
      included. The mean size difference between MRI-GTV and the index tumor was 1.3mm.
      Subclinical disease occurred in 52% and 25% of the specimens at distances >=10mm
      and >=20mm, respectively, from the MRI-GTV. CONCLUSIONS: For MRI-guided minimally
      invasive therapy, typical treatment margins of 10mm around the MRI-GTV may
      include occult disease in 52% of patients. When surgery achieves a 10mm tumor
      free margin around the MRI-GTV, radiotherapy to the tumor bed may require
      clinical target volume margins >10mm in up to one-fourth of the patients.

PMID- 20826027
TI  - Internal target volume defined by contrast-enhanced 4D-CT scan in unresectable
      pancreatic tumour: evaluation and reproducibility.
AB  - We compared customized ITVs obtained with CE-4D-CT imaging (ITV(4D)) with a
      population-based (ITV(PBC)) in 29 patients (PTs) and evaluated the intra-observer
      ITV delineation reproducibility in 5 PTs with unresectable pancreatic ductal
      adenocarcinoma (PDA). The ITV(PBC) was quite different from the ITV(4D), with
      under/over estimation of volume. Intra-observer volume delineation variability on
      CE-4D-CT and on a single-phase CE-CT were similar (27.6% vs 24.9%).

PMID- 20826028
TI  - Influence of dose calculation algorithms on isotoxic dose-escalation of non-small
      cell lung cancer radiotherapy.
AB  - BACKGROUND AND PURPOSE: A series of phase I/II clinical trials are being
      initiated in several UK centres to explore the use of dose-escalated schedules
      for the treatment of non-small cell lung cancer (NSCLC). Among them the IDEAL-CRT
      trial (ISRCTN12155469) will investigate the introduction of individualised
      "isotoxic" treatment schedules based on the relative mean lung normalised total
      dose (rNTD(mean)), an estimator related to lung toxicity. Since treatment
      planning will be performed using different treatment planning systems (TPSs), for
      the quality assurance of the trial we have carried out work to quantify the
      influence of dose calculation algorithms based on the determination of rNTD(mean)
      and on the choice of individualised prescription doses. MATERIAL AND METHODS:
      Twenty-five patient plans with stage I, II and III NSCLC were calculated, with
      the same prescription dose, using the Adaptive Convolve (AC) and Collapsed Cone
      (CC) algorithms of the Pinnacle TPS, the pencil beam convolution (PBC) and AAA
      algorithms of Eclipse, and the CC and pencil beam (PB) algorithms of Oncentra
      Masterplan (OMP). For the paired-lungs-GTV structure, dose-volume histograms were
      obtained and used to calculate the corresponding rNTD(mean) values and results
      obtained with the different algorithms were compared. RESULTS: For most (19 out
      of 25) of the patients studied, no algorithm-to-algorithm differences were seen
      in dose prescription based on rNTD(mean). For the other 6 patients differences
      were within 2.3 Gy, except in one case where the difference was 4 Gy.
      CONCLUSIONS: For the IDEAL-CRT trial no corrections need to be applied to the
      value of rNTD(mean) calculated using any of the more advanced
      convolution/superposition algorithms studied in this work. For the two pencil
      beam algorithms analysed, no correction is necessary for the data obtained with
      the Eclipse-PBC, while for OMP-PB data a small correction needs to be applied, by
      using a scaling factor, to make prescription doses consistent with the other
      algorithms investigated.

PMID- 20826029
TI  - A prospective, randomized, multi-center trial to investigate Actovegin in
      prevention and treatment of acute oral mucositis caused by chemoradiotherapy for
      nasopharyngeal carcinoma.
AB  - PURPOSE: A multi-center prospective randomized trial was conducted to evaluate
      the efficacy and safety of Actovegin in the prevention and treatment of
      chemoradiotherapy-induced acute oral mucositis. METHODS AND MATERIALS: Between
      February 2006 and May 2007, 156 evaluable patients with nasopharyngeal carcinoma
      were randomized to Group 1 (n=53) for prevention, Group 2 (n=51) for treatment,
      and Group 3 (n=52) for control. All patients received concomitant
      chemoradiotherapy +/- induction chemotherapy. Radiation technique and dose were
      similar among 3 groups. Intravenous Actovegin of 30 ml daily (5 days/week) was
      administrated from day 1 of the radiotherapy for Group 1 and from the onset of
      grade 2 mucositis for Group 2, until the end of the radiotherapy. RESULTS: The
      incidence of grade 3 mucositis was lower in Group 1 compared with Group 3 (26.4%
      vs. 55.8%, P=0.002). Group 2 had a lower progression rate of mucositis from grade
      2 to 3 compared with Group 3 (39.2% vs. 60.4%, P=0.035). There was no difference
      in the onset time of grade 3 mucositis among 3 groups. Actovegin was well
      tolerated and no treatment-related adverse events were observed. CONCLUSIONS:
      Actovegin is effective in the prevention and treatment of chemoradiotherapy
      induced oral mucositis.

PMID- 20826030
TI  - Increased use of regional radiotherapy is associated with improved outcome in a
      population-based cohort of women with breast cancer with 1-3 positive nodes.
AB  - PURPOSE: To examine use of and outcomes from adjuvant locoregional radiotherapy
      (LRRT) after breast-conserving surgery (BCS) for women with breast cancer with 1
      3 positive nodes (1-3N+) before and after the 1997 publication of randomised
      trial evidence of a survival advantage from post-mastectomy LRRT. METHODS: Data
      were analysed for 2768 women diagnosed between 1989 and 2005 and referred to the
      British Columbia Cancer Agency with newly diagnosed pT1-3 breast cancer with 1
      3N+, treated with BCS and RT. LRRT use was analysed over time. Ten-year Kaplan
      Meier locoregional control (LRC), breast cancer-specific survival (BCSS) and
      overall survival (OS) curves were compared using the log-rank test. Cox
      regression modeling of LRC and BCSS were performed. RESULTS: LRRT use in patients
      with 1-3N+ increased from 23% before 1997 to 57% after 1997. LRRT was associated
      with significant improvements in LRC, but not in DRFS, BCSS, or OS. 10--year LRC
      was 89% with local RT alone and 93% with LRRT (p=0.006). On multivariable
      analysis, LRRT was associated with improved LRC compared to local RT alone (HR
      0.55, 95% CI: 0.40-0.77), but not with significant BCSS differences. Margin
      status, grade, % positive nodes, and hormonal therapy were significant predictors
      for LRC, while tumour size, grade, % positive nodes, and hormonal therapy
      significantly affected BCSS. CONCLUSION: Post-BCS LRRT use in British Columbia
      increased almost threefold in patients with 1-3N+ after 1997. Adjuvant LRRT was
      associated with improved LRC, but not with improved BCSS compared to breast RT
      alone.

PMID- 20826031
TI  - Characteristics of response of oral and pharyngeal mucosa in patients receiving
      chemo-IMRT for head and neck cancer using hypofractionated accelerated
      radiotherapy.
AB  - PURPOSE: This study describes the acute response of oral and pharyngeal mucosa to
      chemo-IMRT schedules using different doses per fraction. MATERIALS AND METHODS:
      Patients, treated in prospective trials of concomitant chemo-IMRT with 2.17 Gy,
      2.25 Gy and 2.4 Gy per fraction and identical dose of cisplatin, were included in
      this study. Acute toxicity was recorded prospectively using the CTCAE v2.0. We
      describe the incidence and prevalence of grade 3 oral mucositis and dysphagia
      over time and report the influence of overall treatment time (OTT). The
      association between the lengths of pharyngeal mucosa receiving 50 Gy (L50) and 60
      Gy (L60) and grade 3 dysphagia was tested. RESULTS: The incidence and the peak
      prevalence of grade 3 dysphagia were significantly higher in patients receiving
      2.4 Gy per fraction. The peak prevalence of grade 3 dysphagia was higher and the
      recovery was slower in patients with lower OTT (median 38 days vs. 42 days)
      treatment. There was a significant correlation between L50, L60 and grade 3
      dysphagia. A L50 and L60 greater than 8 cm resulted in greater than 60% and 70%
      incidence of grade 3 dysphagia, respectively. CONCLUSION: The length of
      pharyngeal mucosa receiving doses close to the prescription dose correlates with
      grade 3 dysphagia. It was observed that incidence of grade 3 dysphagia was lower
      and recovery from it was quicker in patients with greater OTT.

PMID- 20826032
TI  - Late radiation-induced heart disease after radiotherapy. Clinical importance,
      radiobiological mechanisms and strategies of prevention.
AB  - The clinical importance of radiation-induced heart disease, in particular in post
      operative radiotherapy of breast cancer patients, has been recognised only
      recently. There is general agreement, that a co-ordinated research effort would
      be needed to explore all the potential strategies of how to reduce the late risk
      of radiation-induced heart disease in radiotherapy. This approach would be based,
      on one hand, on a comprehensive understanding of the radiobiological mechanisms
      of radiation-induced heart disease after radiotherapy which would require large
      scale long-term animal experiments with high precision local heart irradiation.
      On the other hand - in close co-operation with mechanistic in vivo research
      studies - clinical studies in patients need to determine the influence of dose
      distribution in the heart on the risk of radiation-induced heart disease. The aim
      of these clinical studies would be to identify the critical structures within the
      organ which need to be spared and their radiation sensitivity as well as a
      potential volume and dose effect. The results of the mechanistic studies might
      also provide concepts of how to modify the gradual progression of radiation
      damage in the heart by drugs or biological molecules. The results of the studies
      in patients would need to also incorporate detailed dosimetric and imaging
      studies in order to develop early indicators of impending radiation-induced heart
      disease which would be a pre-condition to develop sound criteria for treatment
      plan optimisation.

PMID- 20826033
TI  - Preliminary evaluation of infrared spectroscopy for the differentiation of
      Brettanomyces bruxellensis strains isolated from red wines.
AB  - The objective of this study was to evaluate different infrared spectroscopy
      methods in combination with chemometrics for the differentiation between
      Brettanomyces bruxellensis strains. These methods of discrimination were applied
      to intact yeast cells of B. bruxellensis strains and on wines spoiled by the same
      strains. Eleven wine isolates of B. bruxellensis were evaluated for volatile
      phenol production in red wine and their genetic diversity was determined by
      Restriction Endonuclease Analysis-Pulsed Field Gel Electrophoresis (REA-PFGE).
      Fourier transform mid-infrared (FTMIR) spectroscopy was used to obtain spectral
      fingerprints of the spoiled wines. Attenuated total reflectance (ATR) was used to
      obtain spectral fingerprints from the intact cells of the 11 B. bruxellensis
      strains. The groupings from the genetic fingerprints obtained with REA-PFGE were
      used as reference firstly for comparison with the groupings observed with the
      FTMIR spectral fingerprint of the wines and secondly for the FTIR-ATR spectral
      fingerprints from the whole cells. Results indicated that ATR-IR spectra obtained
      by scanning whole cells of B. bruxellensis could be useful for rapid strain
      typing in comparison or complementary to molecular techniques and FTMIR spectra
      from wines provide a useful resource for the discrimination between B.
      bruxellensis contaminated wines.

PMID- 20826034
TI  - Molecular identification of Anisakis type I larvae isolated from hairtail fish
      off the coasts of Taiwan and Japan.
AB  - Anisakid nematodes are known to cause the zoonotic disease, anisakiasis, through
      the consumption of raw or undercooked fish. The parasites most frequently
      associated with the disease in humans are categorized as Anisakis type I, which
      comprise several species of the genus Anisakis. The larvae show primitive forms
      and lack the detailed morphological characteristics required for precise species
      identification. Thus, molecular characterization is necessary for determining the
      species of Anisakis type I larvae and acquiring important clinical and
      epidemiological information. In this study, we isolated Anisakis type I larvae
      from hairtail fish caught off the coasts of Taiwan and Japan. The ribosomal DNA
      (rDNA) internal transcribed spacer (ITS) region was sequenced, and restriction
      fragment length polymorphism (RFLP) analyses using HinfI and HhaI was carried out
      for species identification. Most larvae isolated from hairtail caught in Taiwan
      were Anisakis typica (84%), while those isolated from hairtail caught in Japan
      were almost exclusively identified either as Anisakis simplex sensu stricto (65%)
      or Anisakis pegreffii (33%). This is the first report of A. typica in fish
      obtained from Taiwan. Our results shed the light on the epidemiology of Anisakis
      type I larvae, which is a potential cause of human anisakiasis in Taiwan and
      Japan.

PMID- 20826035
TI  - Fumonisin contamination and fumonisin producing black Aspergilli in dried vine
      fruits of different origin.
AB  - Aspergillus niger isolates are able to produce fumonisins in high quantities on
      agar media with a low water activity. Several agricultural products fit this
      criterion, including dried vine fruits, dates and figs. Data on the occurrence
      and role of this species in fumonisin contamination of agricultural products with
      high sugar content are needed to clarify the importance of A. niger in human
      health. The mycobiota and fumonisin contamination of various dried vine fruit
      samples collected from different countries were examined to clarify the role of
      black Aspergilli in fumonisin contamination of such products. All except two of
      the examined samples were contaminated with black Aspergilli. Species assignment
      of the isolates was carried out using sequence analysis of part of the calmodulin
      gene. The range of fumonisin isomers present in the raisins samples, and produced
      by A. niger isolates collected from dried vine fruits was also examined using
      reversed-phase high-performance liquid chromatography/electrospray ionization-ion
      trap mass spectrometry (RP-HPLC/ESI-ITMS). Among the 30 A. niger/A. awamori
      isolates identified, 20 were found to be able to produce fumonisins (average
      contamination: 5.16 mg/kg; range: 0.017-19.6 mg/kg). The average fumonisin
      content of the 7 dried vine fruit samples which were found to be contaminated by
      potential fumonisin producing black Aspergilli was 7.22 mg/kg (range: 4.55-35.49
      mg/kg). The isolates produced several fumonisin isomers also present in the dried
      vine fruit samples, including fumonisins B(1-4), 3-epi-FB(3), 3-epi-FB(4), iso
      FB(1), and two iso-FB(2,3) forms. Fumonisin B(1) was detected for the first time
      in A. niger cultures. Most of these isomers have previously only been identified
      in Fusarium species. Our data indicate that A. niger and A. awamori are
      responsible for fumonisin contamination of dried vine fruits worldwide. The
      observed levels of contamination are alarming and pose a new threat for food
      safety.

PMID- 20826036
TI  - Bioinformatic tools for using whole genome sequencing as a rapid high resolution
      diagnostic typing tool when tracing bioterror organisms in the food and feed
      chain.
AB  - The rapid technological development in the field of parallel sequencing offers
      new opportunities when tracing and tracking microorganisms in the food and feed
      chain. If a bioterror organism is deliberately spread it is of crucial importance
      to get as much information as possible regarding the strain as fast as possible
      to aid the decision process and select suitable controls, tracing and tracking
      tools. A lot of efforts have been made to sequence multiple strains of potential
      bioterror organisms so there is a relatively large set of reference genomes
      available. This study is focused on how to use parallel sequencing for rapid
      phylogenomic analysis and screen for genetic modifications. A bioinformatic
      methodology has been developed to rapidly analyze sequence data with minimal post
      processing. Instead of assembling the genome, defining genes, defining
      orthologous relations and calculating distances, the present method can achieve a
      similar high resolution directly from the raw sequence data. The method defines
      orthologous sequence reads instead of orthologous genes and the average
      similarity of the core genome (ASC) is calculated. The sequence reads from the
      core and from the non-conserved genomic regions can also be separated for further
      analysis. Finally, the comparison algorithm is used to visualize the phylogenomic
      diversity of the bacterial bioterror organisms Bacillus anthracis and Clostridium
      botulinum using heat plot diagrams.

PMID- 20826037
TI  - A multiplex real-time PCR for identifying and differentiating B. anthracis
      virulent types.
AB  - Bacillus anthracis is closely related to the endospore forming bacteria Bacillus
      cereus and Bacillus thuringiensis. For accurate detection of the life threatening
      pathogen B. anthracis, it is essential to distinguish between these three
      species. Here we present a novel multiplex real-time PCR for simultaneous
      specific identification of B. anthracis and discrimination of different B.
      anthracis virulence types. Specific B. anthracis markers were selected by whole
      genome comparison and different sets of primers and probes with optimal
      characteristic for multiplex detection of the B. anthracis chromosome, the B.
      anthracis pXO1 and pXO2 plasmids and an internal control (IC) were designed. The
      primer sets were evaluated using a panel of B. anthracis strains and exclusivity
      was tested using genetically closely related B. cereus strains. The robustness of
      final primer design was evaluated by laboratories in three different countries
      using five different real-time PCR thermocyclers. Testing of a panel of more than
      20 anthrax strains originating from different locations around the globe,
      including the recent Swedish anthrax outbreak strain, showed that all strains
      were detected correctly.

PMID- 20826038
TI  - In vitro and in vivo antifungal activities of the essential oils of various
      plants against tomato grey mould disease agent Botrytis cinerea.
AB  - The aim of this study was to find an alternative to synthetic fungicides
      currently used in the control of devastating fungal pathogen Botrytis cinerea,
      the causal agent of grey mould disease of tomato. Antifungal activities of
      essential oils obtained from aerial parts of aromatic plants, which belong to the
      Lamiacea family such as origanum (Origanum syriacum L. var. bevanii), lavender
      (Lavandula stoechas L. var. stoechas) and rosemary (Rosmarinus officinalis L.),
      were investigated against B. cinerea. Contact and volatile phase effects of
      different concentrations of the essential oils were found to inhibit the growth
      of B. cinerea in a dose-dependent manner. Volatile phase effects of essential
      oils were consistently found to be more effective on fungal growth than contact
      phase effect. A volatile vapour of origanum oil at 0.2 MUg/ml air was found to
      completely inhibit the growth of B. cinerea. Complete growth inhibition of
      pathogen by essential oil of lavender and rosemary was, however, observed at 1.6
      MUg/ml air concentrations. For the determination of the contact phase effects of
      the tested essential oils, origanum oil at 12.8 MUg/ml was found to inhibit the
      growth of B. cinerea completely. Essential oils of rosemary and lavender were
      inhibitory at relatively higher concentrations (25.6 MUg/ml). Spore germination
      and germ tube elongation were also inhibited by the essential oils tested. Light
      and scanning electron microscopic (SEM) observations revealed that the essential
      oils cause considerable morphological degenerations of the fungal hyphae such as
      cytoplasmic coagulation, vacuolations, hyphal shrivelling and protoplast leakage
      and loss of conidiation. In vivo assays with the origanum essential oil, being
      the most efficient essential oil, under greenhouse conditions using susceptible
      tomato plants resulted in good protection against grey mould severity especially
      as a curative treatment. This study has demonstrated that the essential oils are
      potential and promising antifungal agents which could be used as biofungicide in
      the protection of tomato against B. cinerea.

PMID- 20826039
TI  - Reprint of: Nanoparticles for ex vivo siRNA delivery to dendritic cells for
      cancer vaccines: Programmed endosomal escape and dissociation.
AB  - We previously developed octaarginine (R8)-modified lipid envelope-type
      nanoparticles for siRNA delivery (R8-MEND). Herein, we report on their ex vivo
      siRNA delivery to primary mouse bone marrow-derived dendritic cells (BMDCs) for
      potential use as a cancer vaccine. Quantitative imaging analysis of the
      intracellular trafficking of siRNA revealed that the dissociation process, as
      well as the rate of endosomal escape limits the siRNA efficiency of the prototype
      R8-MEND, prepared by the hydration method (R8-MEND(hydo)). Successful endosomal
      escape was achieved by using a pH-dependent fusogenic peptide (GALA) modified on
      a lipid mixture that was optimized for endosomal fusion. Furthermore, a modified
      protocol for the preparation of nanoparticles, mixing the siRNA/STR-R8 complex
      and small unilamellar vesicles (R8/GALA-MEND(SUV)), results in a more homogenous,
      smaller particle size, and results in a more efficient intracellular
      dissociation. Gene knockdown of the suppressor of cytokine signaling 1 (SOCS1), a
      negative-feedback regulator of the immune response in BMDCs resulted in an
      enhanced phosphorylation of STAT1, and the production of proinflammatory
      cytokines. Moreover, SOCS1-silenced BMDCs were more potent in suppressing tumor
      growth. Collectively, these results show that siRNA loaded in R8/GALA-MEND(SUV)
      efficiently suppresses endogenous gene expression and consequently enhances
      dendritic cell-based vaccine potency in vivo.

PMID- 20826040
TI  - [Incidental detection of a papillary thyroid cancer by 18F-FDG PET-CT study in a
      patient with metastatic colorectal cancer].

PMID- 20826041
TI  - [Granulomatous hepatitis due to Mycobacterium complex following Bacillus Calmette
      Guerin intravesical instillation].

PMID- 20826042
TI  - Student professional suitability: lessons from how the regulator handles fitness
      to practise cases.
AB  - A self regulating profession, such as nursing, has to have in place systems which
      deal with practitioners considered unfit to practise. In addition, students
      studying to enter the profession may also be subject to systems to address
      concerns about their professional suitability. While the NMC have left it up to
      each Higher Education Institution (HEI) to identify the systems which should be
      in place for students, there is a body of case law and statutory legislation
      which governs how the NMC deals with fitness to practise amongst qualified nurses
      and midwives. This paper examines the content of fitness to practise policies in
      place across HEIs and compares this with how the regulator handles fitness to
      practise cases. Data was collected using unobtrusive methods and was analysed
      using content analysis. The results suggest that many HEI's policies have
      significant gaps which may result in challenges to decision making. In addition,
      the power of some Vice Chancellors to overturn fitness to practise decisions on
      appeals calls into question the whole notion of professional self regulation.

PMID- 20826043
TI  - Nursing students' perceptions of tutorial strategies during clinical learning
      instruction: A descriptive study.
AB  - CONTEXT: Teaching strategies and methodology used in clinical training are varied
      and have different levels of outcome. METHODS: A descriptive study was carried
      out in Italy on a convenience sample of third year students at four campuses of
      the Verona University, using a questionnaire divided into four sections:
      trainees' perception of the levels of usefulness of various teaching strategies,
      the levels of effectiveness, the level of supervision and the perceived
      complexity. RESULTS: 308 students compiled the questionnaire. All the tutorial
      strategies included were perceived as having medium to high levels of usefulness,
      ten out of the eleven learning strategies were found to be very useful. A medium
      high level of usefulness was perceived for supervision (M 2.9+/-1). The two
      skills recorded as needing the most supervision were the management of therapy (M
      3.8+/-1.03; Me 4) and performing nursing techniques (M 3.7+/-0.95; Me 4). The
      most complex activities were considered to be confronting an emergency situation
      (M 3.8+/-1.03) and the planning of care for a group of patients (M 3.3+/-0.941),
      and these two activities had had the least amount of supervision. CONCLUSIONS: A
      tutoring model emerged that was centred on learning by experience and with
      guidance.

PMID- 20826044
TI  - Learning preferences of first year nursing and midwifery students: utilising
      VARK.
AB  - The diversity of first year students is increasing with new schemes promoting
      access to higher education courses. It is important to assess the learning styles
      of students in order to cater for their differing learning needs. The aim of this
      study was to profile first year nursing/midwifery students at two campuses of
      Australian Catholic University, to investigate their learning preferences and the
      effect demographic background has on these preferences. We designed a survey to
      collect demographic data and incorporated the VARK (visual, aural, read-write and
      kinaesthetic) questionnaire to investigate the students' preferred learning
      modes. The kinaesthetic score of our students was the highest (7.34 +/- 2.67),
      significantly differing from the other three modes (p<0.001). Demographic factors
      such as gender and age group did not influence mean scores of each sensory
      modality. The predominant preference was quadmodal utilising all four learning
      styles. The distribution of students preferring to learn by unimodal, bimodal,
      trimodal and quadmodal styles varied between demographic groupings. The rural
      students had significantly higher visual and kinaesthetic scores compared to
      their metropolitan counterparts. Students attending the rural campus had higher
      visual and read-write scores. Visual and aural scores were significantly lower
      for students from non-English speaking backgrounds. These findings have
      significant teaching and research implications.

PMID- 20826045
TI  - Effects of amino acid transport limitations on cultured hepatocytes.
AB  - Amino acid supplementation has been shown to enhance the liver-specific functions
      of cultured hepatocytes during plasma exposure. However, their transport through
      the cell membrane may restrict their availability for hepatic metabolism. Here,
      we focus on transport constraints related to uptake of the neutral amino acids
      and their impact on hepatic metabolism and liver-specific functions. Under
      varying combinations of their medium concentrations, we found that transport
      competition exists among the three amino acids alanine, serine and glutamine and
      that the resulting capacity constraints affect the urea and albumin production of
      cultured hepatocytes. Regression equations were developed to quantify these
      constraints and were incorporated with other constraints (mass balance, measured
      flux data and reaction directionality) within a multi-objective flux balance
      framework to understand how amino acid transport constraints propagate through
      central hepatic metabolism and to predict refined amino acid supplementations for
      specific hepatocyte design objectives.

PMID- 20826046
TI  - Cetuximab-conjugated magneto-fluorescent silica nanoparticles for in vivo colon
      cancer targeting and imaging.
AB  - Magneto-fluorescent silica nanoparticles were conjugated with cetuximab for the
      targeting and imaging of colon cancer. In this study, cetuximab-conjugated
      magneto-fluorescent nanoparticles (MFSN-Ctx) could specifically target colon
      cancer cells that expressed EGFR on their cell membranes, and specific
      fluorescence was detected. MFSN-Ctx produced significant MRI signal changes in a
      human colon cancer xenograft mouse model. Intravenous injection of MFSN-Ctx
      resulted in faster uptake as compared to intraperitoneal injection, indicating
      that MFSN-Ctx had different kinetic properties in tumors based on the method of
      injection. The local concentration of MFSN-Ctx in a tumor was amplified by the
      use of an external magnetic field. These results demonstrate the potential
      application of MFSN-Ctx for the detection of EGFR-expressing colon cancer using
      in vivo imaging approaches.

PMID- 20826047
TI  - Galectin inhibitory disaccharides promote tumour immunity in a breast cancer
      model.
AB  - High level galectin-1 expression results in cancer cell evasion of the immune
      response, increased tumour survival and aggressive metastases. Using a galectin-1
      polyclonal antibody, high levels of galectin-1 protein were shown to be expressed
      by breast cancer cells established from FVB/N MMTV-c-neu mice as well as by the
      B16F10 melanoma cell line. In mixed lymphocyte cultures using tumour cells as
      antigenic stimulators, addition of recombinant galectin-1 dose-dependently
      inhibited lymphocyte production. Disaccharides were identified that inhibited
      galectin-1 function and increased growth and activation of CD8(+) CTL's killing
      cancer cells. X-ray crystallographic structures of human galectin-1 in complex
      with inhibitory disaccharides revealed their mode of binding. Combining galectin
      blocking carbohydrates as adjuvants with vaccine immunotherapy in vivo to promote
      immune responses significantly decreased tumour progression and improved the
      outcomes for tumour challenged mice. This is the first report showing that
      suitably selected galectin-1 blocking disaccharides will act as adjuvants
      promoting vaccine stimulated immune responses against tumours in vivo.

PMID- 20826048
TI  - Gender-related disparities in non-small cell lung cancer.
AB  - Epidemiological studies clearly outline some disparities in cancer onset,
      progression as well as prognosis and therapeutic response between sexes. In
      particular, in lung cancer, the leading cause of cancer death, at least in
      Western countries, a gender disparity appears now to emerge, especially for non
      small cell lung cancer (NSCLC). Such a disparity is apparently due to a variety
      of mechanisms, ranging from genetic and epigenetic differences to gender-specific
      lifestyle as well as to behavioral causes and, clearly, to sex hormones activity.
      Here we briefly recapitulate gender differences in terms of risk factors,
      histopathological features and pathogenetic mechanisms in NSCLC, and hypothesize
      that a gender-oriented pharmacology could beneficially impact on innovative
      therapeutic strategies.

PMID- 20826049
TI  - A bispecific antibody effectively inhibits tumor growth and metastasis by
      simultaneous blocking vascular endothelial growth factor A and osteopontin.
AB  - Both vascular endothelial growth factor A (VEGF) and osteopontin (OPN) can
      directly induce tumor angiogenesis, which is essential for the growth and
      metastasis of solid tumors. Here we engineered a bispecific antibody (VEGF/OPN
      BsAb) using the anti-VEGF-A antibody bevacizumab and the anti-OPN antibody
      hu1A12. Compared with hu1A12 alone and bevacizumab alone, VEGF/OPN-BsAb was
      significantly more effective in inhibiting tumor angiogenesis in a highly
      metastatic human hepatocellular carcinoma nude mouse model. Further study
      demonstrated that VEGF/OPN-BsAb could effectively suppress primary tumor growth
      and metastasis to lungs, suggesting that it might be a promising therapeutic
      agent for treatment of metastatic cancer.

PMID- 20826050
TI  - Mouse trophoblastic cells exhibit a dominant invasiveness phenotype over cancer
      cells.
AB  - Invasion process occurs both in mammalian embryo implantation during development
      and malignant cancer cell metastasis. We investigated the interactions between
      trophoblasts and metastatic cancer cells and found the phenomenon that mouse
      trophoblastic cells invaded the monolayer of malignant cancer cells in vitro and
      appeared the general trait of invasiveness to more than 30 types of malignant
      cancer cell lines which were derived from different histological origins and with
      different invasive or metastatic potential. We further investigated the cellular
      and molecular changes in the process of mouse trophoblastic cells invading human
      ovarian cancer HO-8910 cells. The results show that the invasion of trophoblastic
      cells lead HO-8910 cells near mouse embryo to apoptosis, and expression of cell
      cycle-related protein cyclinD1 and Ki-67 mRNA were steadily remained both in
      mouse blastocysts and human ovarian cancer HO-8910 cells, which in part explain
      the proliferation activities of these cells. Our study also shows that expression
      of some proteins including MMP-9, FAK and Integrinalphavbeta3 was changeable in
      trophoblastic cells and HO-8910 cells in the process of blastocyst invasion,
      which suggested temporal expression of these molecules may involved in the
      invasive behavior of trophoblasts cells to cancer cells.

PMID- 20826051
TI  - Who gets high-dose opioid therapy for chronic non-cancer pain?

PMID- 20826053
TI  - Regarding Bell and Moore, intravenous ketamine for CRPS: making too much of too
      little? Pain 2010;150:10-11.

PMID- 20826054
TI  - Questions about Turner et al. Spinal cord stimulation for failed back surgery
      syndrome: outcomes in a worker's compensation setting.

PMID- 20826055
TI  - A money management-based substance use treatment increases valuation of future
      rewards.
AB  - OBJECTIVE: A positive association between delay discounting and substance use has
      been documented; substance users tend to discount future rewards more than non
      users. However, studies detailing the responsiveness of delay discounting to
      interventions are lacking, and few have examined how any behavioral intervention
      affects delay discounting and whether these effects moderate changes in substance
      abuse. This study assesses the effectiveness of a money management intervention,
      Advisor-Teller Money Manager (ATM), in reducing delay discounting over time and
      the relationship of these effects to changes in cocaine use. METHOD: Ninety
      psychiatric patients with histories of cocaine and/or alcohol use were randomly
      assigned to 36-weeks of ATM treatment or to a minimal-attention control
      condition. Delay discounting and cocaine use were measured throughout the
      intervention with a 52-week follow up measure of cocaine use. Analyses were
      conducted of (a) the effect of ATM on slopes of delay discounting and cocaine
      abstinence and (b) the relationship between change in delay discounting and
      change in cocaine abstinence. RESULTS: The ATM intervention was associated with
      significantly less delay discounting and less cocaine use over time relative to
      controls. Increases in delay discounting were associated with decreased
      abstinence from cocaine. CONCLUSIONS: ATM treatment decreased delay discounting
      rates and these effects extended to cocaine use. Concrete conceptualizations of
      future events, as occur in financial planning, with higher perceived probability
      may account for higher valuation of future rewards in counseled patients.

PMID- 20826056
TI  - Structural, concurrent, and predictive validity of the Substance Use Risk Profile
      Scale in early adolescence.
AB  - A brief personality risk profile (23 items), the Substance Use Risk Profile Scale
      was tested for concurrent and predictive validity for substance use in 1139
      adolescents (grades 8-10) from a mid-sized city in western Canada. The SURPS was
      administered in two waves of a longitudinal study separated by 12 months (2003
      04). As expected, four subscales were supported by confirmatory factor and metric
      invariance analysis. In regression analysis, three subscales, hopelessness,
      impulsivity, and sensation seeking, were positively related to current and future
      use; while one, anxiety sensitivity, was negatively related. Findings suggest
      clinical utility for screening adolescents at risk for substance use.

PMID- 20826057
TI  - The combination of morphine and minocycline may be a good treatment for
      intractable post-herpetic neuralgia.
AB  - Post-herpetic neuralgia (PHN) is a devastating complication of shingles. The
      treatment of PHN with traditional pharmaceutical agents has various side effects.
      Therefore, the treatment of intractable PHN is often very time consuming, mainly
      because the available treatments often lead to intolerable side effects before
      the efficient dose can be reached. Opioids such as morphine and oxycodone are the
      most widely used drugs for the alleviation for severe chronic pain. A number of
      high quality studies demonstrated that opioids are effective in relieving
      neuropathic pain including PHN. Yet concerns of misuse, abuse and tolerance of
      opioids have, however, severely influenced their contribution to neuropathic
      pain, especially the tolerance that resulted in a loss of drug effect or the
      necessity for escalating doses to produce pain relief. The glia cells,
      particularly microglia and astrocytes are thought to play an important role in
      central sensitization. It is known that activated microglia cells produce NO,
      cytokines, and cyclooxygenase. All of these chemicals regulate synaptic
      transmissions in the central nervous system. Additionally, glia modulations
      showed antiallodynic and antihyperalgesic properties in various experimental pain
      models. Minocycline, a semisynthetic, second-generation tetracycline can potently
      inhibit microglial activation and proliferation. Also, the growing body of recent
      evidence indicates that minocycline attenuates morphine tolerance in neuropathic
      mice with a mechanism related to microglia. The combination of morphine and
      minocycline has synergetic effect. This can prevent the development of
      intractable PHN and attenuate morphine antinociceptive tolerance and further
      improve the efficacy of morphine and therefore reducing its dosage and side
      effects. We thereby hypothesize that the combination of morphine and minocycline
      may produce a duel effect of morphine antinociceptive and minocycline selectively
      inhibiting the activation of microglia.

PMID- 20826058
TI  - Does transthyretin function as one of contributors for preeclampsia?
AB  - Preeclampsia (PE) is a multi-system disorder of pregnancy, which is characterized
      by new onset hypertension and proteinuria, resulting in multi-organ damages
      within a potential procedure. However as a worldwide leading cause of maternal
      and fetal mortality and morbidity, the precise origin of PE has not been
      clarified yet, which also makes obstacles to the management of the disease.
      Transthyretin (TTR) is a special protein involved in amyloid diseases, has
      important effects on amyloid fibrils formation. We assumed that TTR might cause a
      disorder of maternal vascular function and contributed to the pathology of the
      disease by deposition of TTR amyloid fibrils in the vascular system, which are
      produced by variant TTR proteins, resulting in organ ischemia. If this hypothesis
      proves to be correct, this variant may be of diagnostic importance as novel
      biomarkers for the disease, in addition, it might also benefit to the management
      of PE.

PMID- 20826059
TI  - Identifying placental dysfunction in women with reduced fetal movements can be
      used to predict patients at increased risk of pregnancy complications.
AB  - Maternal perception of fetal movements has historically been used to indicate
      fetal wellbeing, and has been used with varying success in recent years to
      identify those pregnancies at increased risk of stillbirth, and other placental
      pathologies. We present a hypothesis that links reduced fetal movements (RFM) to
      fetal growth restriction (FGR) and stillbirth through placental dysfunction, and
      suggests the possibility that this can allow development of a reliable method to
      identify those women experiencing RFM who are at increased risk of adverse
      outcome. Reduced fetal movement is thought to represent fetal compensation in a
      chronic hypoxic environment due to inadequacies in the placental supply of oxygen
      and nutrients. Placental analysis in FGR and in stillbirth has revealed a number
      of structural abnormalities and an imbalance in cell turnover, and in terms of
      function, FGR is also associated with reduced nutrient transport. Both FGR and
      stillbirth are linked to changes in maternal levels of placental hormones.
      However, no such studies have been performed in samples from pregnancies affected
      by RFM. Currently, there are no formal guidelines to direct the management of
      such women, although it is recommended they undergo measurement of symphysis
      fundal height and cardiotocography, and possibly Doppler ultrasound and
      biophysical profiling. Novel tests could involve the measurement of placental
      derived hormones in maternal serum. To address this hypothesis, macroscopic and
      microscopic analysis of placental samples from both normal pregnancies and those
      affected by RFM is needed to detect any changes in structure. Placental function
      could be evaluated by levels of placental hormones in maternal blood. If
      placental dysfunction can be linked to RFM, and a robust method of identifying
      those women with placental insufficiency can be developed; screening patients
      with RFM could lead to a reduction in perinatal morbidity and mortality.

PMID- 20826060
TI  - Leptin: the link between overweight and primary hyperparathyroidism?
AB  - Primary hyperparathyroidism is one of the most common causes of hypercalcemia.
      Most cases result from sporadic benign monoclonal adenomas or hyperplasia.
      Increased body weight is consistently present in cohorts of patients with primary
      hyperparathyroidism. It has been shown that fat mass is the major determinant of
      serum parathyroid hormone levels independent of vitamin D status. Leptin, an
      adipocyte-derived hormone with mitogenic activity, regulates energy homeostasis
      and mineral metabolism. Serum leptin levels increase in parallel to the amount of
      adipose stores. Interestingly, a positive association between leptin and
      parathyroid hormone levels is observed. Patients with primary hyperparathyroidism
      have higher serum leptin levels than healthy subjects. In addition, leptin
      administration in mice increases circulating levels of parathyroid hormone. We
      hypothesize that leptin involves pathogenesis of primary hyperparathyroidism and
      represents a link between hyperparathyroidism and increased body weight.

PMID- 20826061
TI  - Individual determination of the surgical target for deep brain stimulation in
      obsessive-compulsive disorder.

PMID- 20826062
TI  - Why the tip of vermiform appendix has variable position?

PMID- 20826063
TI  - Personality and illness: genetic connections?
AB  - Illness is strongly influenced by genetics. Personality traits are influenced by
      genetics and have linkages with, at least, affective illness. Because genetics
      influences both personality and illness, we studied by literature review the
      genes that illness and personality traits share and, by office assessment, our
      patient population's illnesses and personality traits. This led to the following
      hypothesis: illness is related to more Submissive than Dominant personality trait
      and thus to lower norepinephrine activity. Patient affect and personality are
      often noted to be subdued in chronic illness, but whether from cause or effect is
      difficult to determine. After reviewing the literature on wellness, personality
      and genes, we endeavored to explore and better delineate our impressions of
      illness and personality relationships and to set the stage for a genetic
      hypothesis by using an online personality test in an ob-gyn practice to determine
      which traits could be used as proxies for personality trait genes. We thus
      confirmed our clinical impression that women with psychiatric and/or medical
      illness have more Submissive personality. The medical literature on gene markers
      shared by Submissive personality and illness in our population suggests the
      hypothesis that this relationship could be mediated by genetically lower
      neurotransmitter activity. Both norepinephrine activity and monoamine oxidase A,
      the enzyme controlling its catabolism, are in concert to blunt neuronal activity
      in such diverse states as depression, asthma, obesity, autoimmune illness, and in
      smokers. Conversely, norepinephrine activity is enhanced in breastfeeders and in
      other settings known to be related to good health. A point for possible
      divergence from the hypothesis is that African-Americans have enhanced
      norepinephrine activity yet poorer health outcomes although the effect of
      environmental risk factors in African-Americans is considered prominent by
      researchers. The possible importance of this hypothesis is that it changes
      emphasis slightly from one of splitting diagnoses to one of grouping them to
      achieve fresh insight. If we assess what is found in common in diverse illnesses
      of mind and body, we have yet another tool to assess causation. Although this
      hypothesis is offered somewhat in a boldness of spirit to take a new look at our
      many perplexing clinical problems, it is also offered with humility in light of
      the complexity with which we deal in patient care.

PMID- 20826064
TI  - Low-intensity pulsed ultrasound: a potential non-invasive therapy for femoral
      head osteonecrosis.
AB  - The osteonecrosis of femoral head (ONFH) has been a common disorder in clinical
      orthopaedic practice. ONFH is the relative contraindication of hip arthroplasty
      for the young and active patients since they suffer a high rate of revision and
      inferior function postoperatively. The primary importance in therapy is to
      prevent the progression of the disease and the collapse of the articular surface
      in order to keep away from hip arthroplasty. Low-intensity pulsed ultrasound
      (LIPUS) has been indicated to enhance the osteogenic differentiation of
      mesenchymal stem cells, stimulate the differentiation and the proliferation of
      osteoblasts, inhibit osteoclasts, improve the local blood perfusion and the
      angiogenesis, and accelerate the healing process of the stress fracture. We
      present a hypothesis that LIPUS may be an appropriate non-invasive modality for
      bone repair in the early stage of ONFH so that the progressive collapse of the
      articular surface and the subsequent arthroplasty would be avoided.

PMID- 20826065
TI  - A combined candidate therapy for the scar-free repair of cleft lip based on
      inhibitors of TGF-beta.
AB  - The prevalence of cleft lip with or without cleft palate (CL/P) at birth varied
      from 3.4-22.9 per 10000 births according to different geography and ethnic
      groups. And scar has been recognized as a significantly negative factor on the
      postoperative wound healing of cleft lip patients because it often impairs
      function, blocks growth and makes the face aesthetically unpleasant. TGF-beta
      (Transforming growth factor-beta), a chemotactic factor of monocytes, fibroblasts
      and macrophages, which stimulates collagen and other extracellular matrix
      deposition by fibroblasts, could promote angiogenesis and stimulate the scar
      formation, which hinder the aesthetic effects on the face. Theoretically,
      inhibitors of TGF-beta could inhibit scar formation, which could be a potential
      application for the therapy of cleft lip patients. Therefore a combined therapy
      based on inhibitors of TGF-beta may be taken as an important treatment to control
      postoperative scar in the future.

PMID- 20826066
TI  - Treg-based therapy and mixed chimerism in small intestinal transplantation: does
      Treg +BMT equal intestine allograft tolerance?
AB  - Small intestinal transplantation (SIT) is a convincing treatment selection for
      end-stage bowel failure, however, graft rejection and the toxicity associated
      with the use of non-specific immunosuppression remain the major limitations in
      SIT. Induction of SIT tolerance through establishment of mixed chimeras is
      regarded as a robust approach to solve this problem. In rodent models of
      nonmyeloablative recipient preparation using donor bone marrow transplant
      (BMT)+costimulatory blockade, deletion of alloreactive T cells played the
      dominant role in silencing the effector function of graft-rejecting T cells.
      However, such understanding of the cellular basis for allograft tolerance might
      be incomplete. Several recent studies demonstrated that regulatory T cells
      (Tregs) could promote the establishment of allogeneic mixed chimerism as well as
      the induction of donor-specific tolerance. Treg-based therapy in and of itself is
      proposed to be a promising non-toxic approach to prevent allograft from
      rejection. In addition, latest studies showed that, Tregs not only played a
      critical role in controlling both acute and chronic rejection, but also might
      contribute to the protection of allograft from ischemia/reperfusion injury (IRI).
      Taken together, we hypothesize that, co-transplant of donor bone marrow and Tregs
      specific for alloantigens might be one of the most effective regimens to induce
      transplantation tolerance, so as to improve the overall outcome of SIT. Although
      much efforts have been made, a deliberate protocol without toxicity still needs
      to be developed for the clinical application.

PMID- 20826067
TI  - NK-1-receptor-mediated lesion of spinal post-synaptic dorsal column neurons might
      improve intractable visceral pain of cancer origin.
AB  - The cancer-related visceral pain has traditionally been frustrating to treat by
      either medical or surgical means. Recent investigations from bench and bedside
      have suggested that a critical visceral nociceptive pathway originates from post
      synaptic dorsal column (PSDC) neurons located in the central area of the spinal
      cord. Interruption of the PSDC pathway using different surgical approaches
      effectively relieves intractable visceral pain in cancer patients. However, the
      indications of surgical lesion of DC are very limited in clinical setting because
      of the surgical risks and complications. Thus, a means of high-specific
      pharmacological lesion of DC pathway is necessary. Some evidence has shown that
      spinal PSDC neurons start to express neurokinin-1 (NK-1) receptors after visceral
      stimulation, suggesting new targets for the development of pharmacological
      strategies for the control of visceral pain. Here, we present our hypothesis that
      the targeted cytoxin composed of substance P coupled to the cytotoxic ribosome
      inactivating protein, saporin, might selectively destroy spinal PSDC neurons
      expressing NK-1 receptors, which will lead to pharmacological interruption of
      PSDC pathway and will greatly improve intractable visceral pain of cancer origin.
      Based on the data from related research, we believe that the current therapy we
      propose might be one of the optimal pharmacological approaches to replace the
      neurosurgical interruption of DC pathway and could be used for cancer-related
      visceral pain in wider clinical indications.

PMID- 20826068
TI  - Updated estimates of HAL n and RN- effects on pork quality: fresh and processed
      loin and ham.
AB  - A 1000-pig F2 intercross QTL detection experimental population was generated
      using two commercial sire lines. Independent carriers of HAL n and RN- mutations
      (10% and 14%, respectively) were included in this population as control
      genotypes. The effects of HAL n and RN- heterozygous genotypes on fresh and
      transformed loins and hams were estimated using a mixed model methodology. The
      results document the unfavorable effects of both mutations on meat quality.
      Smaller effects of HAL Nn genotype compared to HAL nn or RN-rn+ genotypes were
      estimated. Interestingly, effects of HAL Nn genotype on meat pH and loin color
      could be insignificant at 24-h postmortem, but translate into higher water losses
      on storage and cooking, and result in tougher cooked loin. Using the same
      methodology, significant effects of the PRKAG3 (RN) I199 allele on ultimate pH
      values but not on glycolytic potential were observed.

PMID- 20826069
TI  - Effect of bamboo salt on the physicochemical properties of meat emulsion systems.
AB  - This study was conducted to determine the effects of various bamboo salts on meat
      batter. To accomplish this, three different batters were prepared and compared:
      CON, which was prepared with NaCl, BS-2, which was prepared with bamboo salt that
      was baked twice, BS-9, which was prepared with bamboo salt that was baked nine
      times. The pH of both the uncooked and cooked BS-2 and BS-9 was higher than that
      of the CON (P<0.05). The emulsion stability, cooking yield, water holding
      capacity (WHC) and apparent viscosity of BS-2 and BS-9 were higher than those of
      CON. The correlation coefficient between the viscosity value and WHC was high and
      positive (R(2)=0.672). The hardness of all treatments was significantly increased
      with increased cooking temperature (P<0.05). The hardness, gumminess and
      chewiness of CON were higher than that of BS-9 and BS-2. The overall
      acceptability score between CON and BS-9 was significantly different (P<0.05).
      The bamboo salts effectively improved the physicochemical properties of the meat
      batter.

PMID- 20826070
TI  - Near infrared spectroscopy as an on-line method to quantitatively determine
      glycogen and predict ultimate pH in pre rigor bovine M. longissimus dorsi.
AB  - The potential of near infrared (NIR) spectroscopy as an on-line method to
      quantify glycogen and predict ultimate pH (pH(u)) of pre rigor beef M.
      longissimus dorsi (LD) was assessed. NIR spectra (538 to 1677 nm) of pre rigor LD
      from steers, cows and bulls were collected early post mortem and measurements
      were made for pre rigor glycogen concentration and pH(u). Spectral and measured
      data were combined to develop models to quantify glycogen and predict the pH(u)
      of pre rigor LD. NIR spectra and pre rigor predicted values obtained from
      quantitative models were shown to be poorly correlated against glycogen and pH(u)
      (r(2)=0.23 and 0.20, respectively). Qualitative models developed to categorize
      each muscle according to their pH(u) were able to correctly categorize 42% of
      high pH(u) samples. Optimum qualitative and quantitative models derived from NIR
      spectra found low correlation between predicted values and reference
      measurements.

PMID- 20826071
TI  - Associations between single nucleotide polymorphisms in multiple candidate genes
      and carcass and meat quality traits in a commercial Angus-cross population.
AB  - The aim of this study was to evaluate the effects of 28 single nucleotide
      polymorphisms (SNP) in 10 candidate genes previously shown to be associated with
      quality traits in pigs and cattle. The data set comprised 28 traits recorded on a
      commercial population of 536 Aberdeen Angus-cross beef cattle. Among the traits,
      20 were carcass and sirloin quality related, one mechanical measure of
      tenderness, and the remaining seven were taste panel assessed sensory traits. The
      candidate genes studied included growth hormone (GH) and pro-opiomelanocortin
      (POMC). Association analysis showed that 13 of the 28 SNPs were significantly
      associated with at least one of the traits. Some of these were novel (POMC and
      mechanical tenderness), whilst others confirmed previous results (GH and eye
      muscle length). Following validation in other populations and breeds, these
      markers could be incorporated into breeding programs to increase the rate of
      improvement in carcass and meat quality traits.

PMID- 20826072
TI  - Encouraging breastfeeding: A relational perspective.
AB  - Despite the WHO recommendations that babies should be breastfed exclusively for
      six months and thereafter for up to two years and beyond this pattern of feeding
      is far from the global norm. Although breastfeeding is triggered through
      biological mechanisms which have not changed with time, the perception of
      breastfeeding as a phenomenon is variable, as it not only reflects cultural
      values of motherhood but is also negotiable from the perspective of the
      individual. This paper argues that relationships are central to encouraging
      breastfeeding at an organisational, family and staff-parent level. This shifts
      our conceptualisations away from the primary focus of breastfeeding as nutrition
      which, in turn, removes the notion of breastfeeding as a productive process,
      prone to problems and failure.

PMID- 20826073
TI  - Small and large foetuses: Identification and estimation of foetal weight at
      delivery from third-trimester ultrasound data.
AB  - BACKGROUND: The estimation of foetal weight (EFW) at delivery is crucial to
      assess the risk of foetal and neonatal morbidity and mortality, most notably when
      the foetus is small or large. AIM: To accurately predict the EFW at delivery of
      small foetuses (birth weight [BW]<=2500g) and large foetuses (BW>=4000g)
      identified with third-trimester ultrasound data. METHODS: We included 1309
      foetuses whose age and weight at birth were known and for whom standard data were
      available from third-trimester ultrasound scans. Small and large foetuses were
      identified by extrapolation to full term of the estimated foetal weight obtained
      using Hadlock's equation. We built two regression models for predicting the birth
      weights of small and large foetuses, respectively. The results obtained with
      these models were compared to those obtained with Hadlock's equation. RESULTS:
      Third-trimester sonograms were obtained at 33.6+/-1.3 weeks gestational age [WGA]
      and birth occurred at 38.7+/-1.2WGA. EFW of small foetuses predicted using the
      regression model showed significantly less systematic bias than the Hadlock
      estimate (2.3% vs. 7.2%, respectively), whereas random errors were similar. EFW
      of large foetuses predicted using the regression model showed significantly less
      random error than the Hadlock estimate (6.2% vs. 10.1%, respectively), whereas
      systematic bias was similar. Data from an independent validation sample indicate
      that our regression models are accurate. CONCLUSIONS: To apply distinct models
      for accurately predicting the EFWs at delivery of small and large foetuses should
      prevent adverse events related to newborn size.

PMID- 20826074
TI  - Absence of small-vessel abnormalities in alternating hemiplegia of childhood.
AB  - OBJECTIVE: To investigate whether Japanese patients with alternating hemiplegia
      of childhood (AHC) have the similar small-vessel abnormalities in skin reported
      in European patients with AHC. METHODS: Electron microscopic observation of
      biopsied skin specimens were carried out in six Japanese patients with AHC. All
      patients (aged 5-17, all boys) had been diagnosed with AHC through their typical
      clinical courses and symptoms. RESULTS: No abnormal findings in both endothelial
      cells and smooth muscle cells in skin small-vessels were obtained in the present
      study, either in the five flunarizine responders or in the one non-responder.
      CONCLUSIONS: From our observations, we hypothesized that there may be some
      subtypes of AHC. The diverse clinical courses in patients with AHC and the
      differing efficacy of flunarizine treatment could be explained because of the
      heterogeneity of AHC subtypes.

PMID- 20826075
TI  - Correlation between EEG abnormalities and symptoms of autism spectrum disorder
      (ASD).
AB  - Children with ASD often suffer from epilepsy and paroxysmal EEG abnormality.
      Purposes of this study are the confirmation of incidence of epileptic seizures
      and EEG abnormalities in children with autism using a high performance digital
      EEG, to examine the nature of EEG abnormalities such as locus or modality, and to
      determine if the development of children with ASD, who have experienced
      developmental delay, improves when their epilepsy has been treated and maintained
      under control. A total of 1014 autistic children that have been treated and
      followed-up for more than 3 years at Yasuhara Children's Clinic in Osaka, Japan,
      were included in this study. Each participant's EEG had been recorded
      approximately every 6 months under sleep conditions. Epilepsy was diagnosed in
      37% (375/1014) of the study participants. Almost all patients diagnosed with
      epilepsy presented with symptomatic epilepsy. The data showed that the
      participants with lower IQ had a higher incidence of epileptic seizures.
      Epileptic EEG discharges occurred in 85.8% (870/1014) of the patients. There was
      also a very high incidence of spike discharges in participants whose intellectual
      quotient was very low or low. Epileptic seizure waves most frequently developed
      from the frontal lobe (65.6%), including the front pole (Fp1 and Fp2), frontal
      part (F3, F4, F7 and F8) and central part (C3, Cz and C4). The occurrence rate of
      spike discharges in other locations, including temporal lobe (T3, T4, T5, T6),
      parietal lobe (P3, Pz, P4), occipital lobe (O1, O2) and multifocal spikes was
      less than 10%. These results support the notion that there is a relationship
      between ASD and dysfunction of the mirror neuron system. The management of
      seizure waves in children diagnosed with ASD may result in improves function and
      reduction of autistic symptoms.

PMID- 20826076
TI  - Predicting nonresponse to juvenile drug court interventions.
AB  - Using data from a recent randomized clinical trial involving juvenile drug court
      (JDC), youth marijuana use trajectories and the predictors of treatment
      nonresponse were examined. Participants were 118 juvenile offenders meeting
      diagnostic criteria for substance use disorders assigned to JDC and their
      families. Urine drug screen results were gathered from weekly court visits for 6
      months, and youth reported their marijuana use over 12 months. Semiparametric
      mixture modeling jointly estimated and classified trajectories of both marijuana
      use indices. Youth were classified into responder versus nonresponder trajectory
      groups based on both outcomes. Regression analyses examined pretreatment
      individual, family, and extrafamilial predictors of nonresponse. Results
      indicated that youth whose caregivers reported illegal drug use pretreatment were
      almost 10 times as likely to be classified into the nonresponder trajectory
      group. No other variable significantly distinguished drug use trajectory groups.
      Findings have implications for the design of interventions to improve JDC
      outcomes.

PMID- 20826077
TI  - Slow wave sleep deficits as a trait marker in patients with schizophrenia.
AB  - BACKGROUND: Among the sleep abnormalities found in schizophrenia, slow wave sleep
      deficits have been found to persist even after the resolution of active psychotic
      symptoms. Further, such abnormalities are observed in young healthy individuals
      at high risk of schizophrenia, which suggest that slow wave sleep deficits might
      be trait marker in schizophrenia. METHODS: Sleep EEG was recorded in 20 right
      handed patients aged 18-45 years with ICD-10 DCR diagnosis of schizophrenia, 14
      first degree relatives and 20 age and sex matched controls. Patients were rated
      on Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating
      Scale (BPRS) for assessment of psychopathology. RESULTS: There was significant
      difference between the three groups in total sleep period (p<.01), total sleep
      time (p<.01), stage shifts (p<.05), stage 1 percentage of total sleep time
      (p<.05), stage 2 duration (p<.05), stage 3 latency (p<.05), stage 4 duration
      (p<.01) and stage 4 percentage of total sleep time (p<.01). There was significant
      positive correlation of REM percentage of total sleep time with BPRS total score
      (r(s) = .488, p = .029) and PANSS positive score (r(s) = .583, p = .007), whereas
      significant negative correlation of REM latency was found with BPRS total score
      (r(s) = -.640, p = .002) and PANSS positive score (r(s) = -.657, p = .002) in the
      patients. CONCLUSIONS: Slow wave sleep deficits are a possible trait marker in
      patients with schizophrenia, which needs replication in further studies.

PMID- 20826078
TI  - Neuroanatomical correlates of executive dysfunction in the at-risk mental state
      for psychosis.
AB  - Deficits in executive functioning have been described as a core feature of
      schizophrenia and have been linked to patterns of fronto-temporo-limbic brain
      alterations. To date, such structure-cognition relationships have not been
      explored in a clinically defined at-risk mental state (ARMS) for psychosis using
      whole-brain neuroimaging techniques. Therefore, we used voxel-based morphometry
      in 40 ARMS and 30 matched healthy control (HC) individuals to investigate whether
      gray and white matter volumes (1) correlated with the performance in the Trail
      Making Test B (TMT-B), an established measure of executive functioning, and (2)
      were volumetrically linked to the ventromedial prefrontal cortex (VMPFC), found
      to be associated with TMT-B in the ARMS during the first analysis step. We found
      the ARMS subjects to be specifically impaired in their TMT-B performance versus
      HC. Brain-cognition associations involving the insular cortices were observed in
      the HC, but not in the ARMS individuals. Conversely, TMT-B correlations in the
      VMPFC, the cerebellum, the fronto-callosal white matter were detected in the
      ARMS, but not the HC group. The VMPFC was linked to the temporo-limbic cortices
      in HC, whereas the connectivity pattern in the ARMS involved the left temporal
      and dorsolateral prefrontal cortex, the cerebellum, the right SMA and extended
      portions of the fronto-callosal white matter. These findings suggest that
      executive deficits are already present in the ARMS for psychosis and may be
      subserved by structurally altered networks of interconnected cortical and
      subcortical brain regions in line with the disconnectivity hypothesis of
      schizophrenia.

PMID- 20826079
TI  - Cannabis use and cognitive functioning in first-episode schizophrenia patients.
AB  - Cannabis is one of the most widely used illicit drugs in the world. In healthy
      individuals cannabis is associated with cognitive impairments. Research into the
      effect of cannabis use in schizophrenia has yielded contradictory findings. Our
      aim has been to explore the correlates of cannabis use in cognitive and
      psychopathological features, both cross-sectional and longitudinally, in early
      phases of schizophrenia. 104 patients with a first episode of non-affective
      psychosis and 37 healthy controls were studied. Patients were classified
      according to their use of cannabis prior to the onset of the illness (47 users
      vs. 57 non-users). They were cross-sectionally and longitudinally studied and
      compared on clinical and cognitive variables and also on their level of premorbid
      adjustment. Cannabis user patients had better attention and executive functions
      than non-cannabis user patients at baseline and after 1 year of treatment. Both
      groups showed similar improvement in their cognitive functioning during the 1
      year follow-up period. We also found that users had a better social premorbid
      adjustment, particularly during the early periods of life. The amount of cannabis
      consumed and the length of time of consumption did not significantly relate to
      cognitive performance. The use of cannabis does not seem to be associated with a
      negative effect on cognition in a representative sample of first-episode
      schizophrenia patients. Cannabis user patients appear to comprise a subgroup of
      patients with a better premorbid adjustment and premorbid frontal cognitive
      functions.

PMID- 20826081
TI  - Evaluation of the geotechnical properties of MSW in two Brazilian landfills.
AB  - The characteristics of municipal solid waste (MSW) play a key role in many
      aspects of waste disposal facilities and landfills. Because most of a landfill is
      made up of MSW, the overall stability of the landfill slopes are governed by the
      strength parameters and physical properties of the MSW. These parameters are also
      important in interactions involving the waste body and the landfill structures:
      cover liner, leachate and gas collection systems. On the other hand, the
      composition of the waste, which affects the geotechnical behavior of the MSW, is
      dependent on a variety of factors such as climate, disposal technology, the
      culture and habits of the local community. It is therefore essential that the
      design and stability evaluations of landfills in each region be performed based
      on the local conditions and the geotechnical characteristic of the MSW. The
      Bandeirantes Landfill, BL, in Sao Paulo and the Metropolitan Center Landfill,
      MCL, in Salvador, are among the biggest landfills in Brazil. These two disposal
      facilities have been used for the development of research involving waste
      mechanics in recent years. Considerable work has been made in the laboratory and
      in the field to evaluate parameters such as water and organic contents,
      composition, permeability, and shear strength. This paper shows and analyzes the
      results of tests performed on these two landfills. The authors believe that these
      results could be a good reference for certain aspects and geotechnical properties
      of MSW materials in countries with similar conditions.

PMID- 20826080
TI  - Selenoprotein P protects cells from lipid hydroperoxides generated by 15-LOX-1.
AB  - Reactive lipid hydroperoxides formed by lipoxygenases and cyclooxygenases can
      contribute to disease through cellular oxidative damage. Several selenoproteins
      have lipid hydroperoxidase activity, including glutathione peroxidase 4,
      thioredoxin reductase, and selenoprotein P (SelP). SelP is an extracellular
      glycoprotein that functions both in selenium distribution and has an antioxidant
      activity. The major objective of this study was to determine if an SelP, at
      physiological concentrations and in selenium replete media, possessed
      hydroperoxidase activity directed at lipid hydroperoxides generated from the
      metabolism of arachidonic acid by 15-lipoxygenase-1 (15-LOX-1). An SelP displayed
      in vitro lipid hydroperoxidase activity of 15-hydroperoxyeicosatetraenoic acid
      (15-HpETE), attenuated 15-HpETE oxidation in cellular assays, and in
      transcellular assay when 15-LOX-1 is metabolically active. These results suggest
      that an SelP can function as an antioxidant enzyme against reactive lipid
      intermediates formed during inflammation, but an SelP has modest activity.
      Nevertheless, this effect may help protect cells against the oxidative damage
      induced by these lipid metabolites.

PMID- 20826082
TI  - Characterization of organic particulates present in milk factory process waters
      used for reuse along with aerobically digested effluent wastewater.
AB  - Wastewater from a dairy processor is being reused and recycled both within the
      plant and for irrigation. Flash pyrolysis GC-MS was used to examine nitrogen and
      phenol containing compounds (M.W.=35 to 450 g/mol) in the particulate fraction of
      the milk condensate, combined clean wastewater and aerobic bioreactor effluent.
      For comparison, the particulates were also prepared for standard GC-MS analyses
      using conventional solvent extraction methods. Compounds detected by pyrolysis GC
      MS were found mostly in the bioreactor with the amino acid arginine (220 mg/kg)
      and the amino acid derivative 1-methyl-5-oxo-L-proline methyl ester (130 mg/kg)
      found at the highest concentrations. In comparison, sterols detected in the
      effluent were found at higher concentrations when using solvent extraction
      indicating some degradation with pyrolysis GC-MS. However, with few exceptions,
      particulates were generally found not to act as passive collectors capable of
      concentrating less water soluble chemicals.

PMID- 20826083
TI  - Influence of vegetable oils fatty-acid composition on biodiesel optimization.
AB  - Biodiesel is an alternative fuel for diesel engines produced through
      transesterification of oleaginous feedstocks. To analyze the influence of the
      fatty-acid composition on biodiesel optimization, transesterification of several
      vegetable oils has been studied. Reactions were carried out in flasks filled with
      vegetable oils, heated to the reaction temperature and stirred at 1100 rpm. The
      reactions started when the methanol and potassium hydroxide solutions were added
      to the flasks. Concentration of catalyst, amount of methanol, reaction
      temperature and time were optimized using a factorial design and a surface
      response design. Also, a kinetics study was carried out to optimize the reaction
      time. Results showed that reaction parameters optimal values depend on the oil
      chemical and physical properties. It can be concluded from this field trial that
      the effect of both catalyst concentration and reaction time over the
      transesterification yield is greatly influenced by the saturation degree and
      fatty-acid chain length.

PMID- 20826084
TI  - Bio-hydrogen production by Chlorella vulgaris under diverse photoperiods.
AB  - The hydrogen production by Chlorella vulgaris exposed to four different light
      patterns was explored. Cultures of immobilized, sulfur-deprived cells were purged
      with N2 and either kept in the dark for 72 h, kept in the dark for 24 h before
      being exposed to light (intensity of 120 MU mole/m2/s) for 72 h, exposed to light
      for 72 h, or kept in the light for 24h before being subjected to darkness for 48
      h. The latter condition provided for the highest total hydrogen production of
      530+/-5 ml/l of medium and a maximum hydrogen release rate of 34.8 ml/h/l. Growth
      for 72 h under partial light conditions was essential for continuous and enhanced
      hydrogen production. The addition of glucose to the sulfur-deficient medium
      increased hydrogen production by 18 times under partial light condition. To
      increase the hydrogen productivity, a carbon source may be added to enhance
      hydrogen production.

PMID- 20826085
TI  - Dilute acid pretreatment of rapeseed straw for fermentable sugar generation.
AB  - The influence of the main pretreatment variables on fermentable sugar generation
      from rapeseed straw is studied using an experimental design approach. Low and
      high levels for pretreatment temperature (140-200  degrees C), process time (0-20
      min) and concentration of sulfuric acid (0.5-2% w/v) were selected according to
      previous results. Glucose and xylose composition, as well as sugar degradation,
      were monitored and adjusted to a quadratic model. Non-sugar components of the
      hydrolysates were also determined. Enzymatic hydrolysis yields were used for
      assessing pretreatment performance. Optimization based on the mathematical model
      show that total conversion of cellulose from pretreated solids can be achieved at
      pretreatment conditions of 200  degrees C for 27 min and 0.40% free acid
      concentration. If optimization criteria were based on maximization of
      hemicellulosic sugars recovery in the hydrolysate along with cellulose
      preservation in the pretreated solids, milder pretreatment conditions of 144 
      degrees C, 6 min and 2% free acid concentration should be used.

PMID- 20826086
TI  - Evaluating the impact of ammonia fiber expansion (AFEX) pretreatment conditions
      on the cost of ethanol production.
AB  - Ammonia fiber expansion (AFEX) pretreatment is an ammonia-based process for
      improving the susceptibility of lignocellulosic biomass to enzymatic attack. Four
      parameters--ammonia loading, water loading, reaction temperature, and residence
      time--can be varied in order to optimize AFEX pretreatment. The effect of these
      parameters on process economics of ethanol production was studied using a leading
      biorefinery model. Ammonia loading and residence time had the greatest impact on
      the economics of ethanol production, primarily due to processing costs for the
      chilled water condenser and the capital cost of the AFEX reactor. Water loading
      and reaction temperature had only modest impact on process economics. In
      addition, the impact of pretreatment conditions on makeup ammonia requirements
      was explored experimentally, which ranged from 15 to 25 g ammonia/kg biomass.
      Overall, pretreatment conditions can change the costs of ethanol production by up
      to 35 cents per gallon ethanol in an 850 ton/day refinery. By linking the results
      obtained from this Aspen model to experimental results for ethanol production and
      makeup ammonia recovery, this study can be used to create an economic optimum for
      AFEX pretreatment in contrast with simply maximizing fermentable sugar
      production.

PMID- 20826087
TI  - Radiosensitization of cancer cells by hydroxychalcones.
AB  - Radiation sensitization is significantly increased by proteotoxic stress, such as
      a heat shock. We undertook an investigation, seeking to identify natural products
      that induced proteotoxic stress and then determined if a compound exhibited
      radiosensitizing properties. The hydroxychalcones, 2',5'-dihydroxychalcone (D
      601) and 2,2'-dihydroxychalcone (D-501), were found to activate heat shock factor
      1 (Hsf1) and exhibited radiation sensitization properties in colon and pancreatic
      cancer cells. The radiosensitization ability of D-601 was blocked by pretreatment
      with alpha-napthoflavone (ANF), a specific inhibitor of cytochrome P450 1A2
      (CYP1A2), suggesting that the metabolite of D-601 is essential for
      radiosensitization. The study demonstrated the ability of hydroxychalcones to
      radiosensitize cancer cells and provides new leads for developing novel radiation
      sensitizers.

PMID- 20826088
TI  - On the use of 2,1,3-benzothiadiazole derivatives as selective live cell
      fluorescence imaging probes.
AB  - Newly designed 2,1,3-benzothiadiazole-containing fluorescent probes with four
      excited state intramolecular proton transfer (ESIPT) sites were successfully
      tested in live cell-imaging assays using a confluent monolayer of human stem
      cells (tissue). All tested dyes were compared with the commercially available
      DAPI and gave far better results.

PMID- 20826089
TI  - A mimic of the pyruvate dehydrogenase complex.
AB  - Pyruvic acid undergo decarboxylation catalyzed by a hydrophobic thiazolium salt
      and reacts with a hydrophobic analog of lipoic acid to form a hydrophobic
      acylthioester that reacts with aniline to form acetanilide in water, but only in
      the presence of a hydrophobically modified polyaziridine that acts to gather the
      reactants just as the enzyme complex does.

PMID- 20826090
TI  - Design, synthesis, and binding of homologated truncated 4'-thioadenosine
      derivatives at the human A3 adenosine receptors.
AB  - We synthesized homologated truncated 4'-thioadenosine analogues 3 in which a
      methylene (CH(2)) group was inserted in place of the glycosidic bond of a potent
      and selective A(3) adenosine receptor antagonist 2. The analogues were designed
      to induce maximum binding interaction in the binding site of the A(3) adenosine
      receptor. However, all homologated nucleosides were devoid of binding affinity at
      all subtypes of adenosine receptors, indicating that free rotation through the
      single bond allowed the compound to adopt an indefinite number of conformations,
      disrupting the favorable binding interaction essential for receptor recognition.

PMID- 20826091
TI  - 20-Aminosteroids as a novel class of selective and complete androgen receptor
      antagonists and inhibitors of prostate cancer cell growth.
AB  - Here, the synthesis and the evaluation of novel 20-aminosteroids on androgen
      receptor (AR) activity is reported. Compounds 11 and 18 of the series inhibit
      both the wild type and the T877A mutant AR-mediated transactivation indicating AR
      antagonistic function. Interestingly, minor structural changes such as
      stereoisomers of the amino lactame moiety exhibit preferences for antagonism
      among wild type and mutant AR. Other tested nuclear receptors are only weakly or
      not affected. In line with this, the prostate cancer cell growth of androgen
      dependent but not of cancer cells lacking expression of the AR is inhibited.
      Further, the expression of the prostate specific antigen used as a diagnostic
      marker is also repressed. Finally steroid 18 enhances cellular senescence that
      might explain in part the growth inhibition mediated by this derivative. Steroids
      11 and 18 are the first steroids that act as complete AR antagonists and exhibit
      AR specificity.

PMID- 20826092
TI  - Sedimentation rates in Atibaia River basin, Sao Paulo State, Brazil, using 210Pb
      as geochronometer.
AB  - The constant initial concentration (CIC) of unsupported/excess (210)Pb model was
      successfully used to assess (210)Pb data of nine sediment cores from Atibaia
      River basin, Sao Paulo State, Brazil. The (210)Pb-based apparent sediment mass
      accumulation rates ranged from 47.7 to 782.4 mg/cm(2)yr, whereas the average
      linear sedimentation rates between 0.16 and 1.32 cm/yr, which are compatible with
      the calculated sediment mass fluxes, i.e. a higher sediment mass accumulation
      rate yielded a higher linear sedimentation rate. The higher long-term based
      accumulation rate tended to be found in topographically softer regions. This
      occurs because the sediments are preferentially transported in topographically
      steeper regions instead of being deposited. Anthropic activities like
      deforestation possibly interfered with the natural/normal sedimentation
      processes, which increased in accordance with modifications on the channel
      drainage. The radionuclide geochronology as described in this paper allows
      determination of sedimentation rates that are compatible with values estimated
      elsewhere. The adoption of an appropriate factor generated from previous
      laboratory experiments resulted in a successful correction for the (222)Rn-loss
      from the sediments, bringing the estimate of the parent-supported (in-situ
      produced) (210)Pb to reliable values required by the CIC model.

PMID- 20826093
TI  - Effects of molecular weight and ratio of guluronic acid to mannuronic acid on the
      antioxidant properties of sodium alginate fractions prepared by radiation-induced
      degradation.
AB  - In this study, the effects of the molecular weight and ratio of guluronic acid
      (G) to mannuronic acid (M), G/M, of some sodium alginate (NaAlg) fractions on
      their antioxidative properties were investigated. Low-molecular-weight-fractions
      with various G/M were prepared by gamma radiation-induced degradation of NaAlg.
      Change in their molecular weight was monitored. Antioxidant properties of the
      fractions with various molecular weight and G/M were evaluated by determining the
      scavenging ability of 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH()). 50%
      inhibition concentrations of the 50 kGy-irradiated NaAlgs having molecular
      weights of 20.5, 17.7, and 16.0 kDa were found to be 11.0, 18.0, and 24.0mg/ml,
      respectively, whereas the fractions of the same molecular weight with a lower G/M
      exhibited a better DPPH() scavenging activity. The results demonstrated that its
      molecular weight and G/M were important factors in controlling the antioxidant
      properties of NaAlg.

PMID- 20826094
TI  - Multiple indicators of ambient and personal ultraviolet radiation exposure and
      risk of non-Hodgkin lymphoma (United States).
AB  - Recent epidemiologic studies have suggested that ultraviolet radiation (UV) may
      protect against non-Hodgkin lymphoma (NHL), but few, if any, have assessed
      multiple indicators of ambient and personal UV exposure. Using the US Radiologic
      Technologists study, we examined the association between NHL and self-reported
      time outdoors in summer, as well as average year-round and seasonal ambient
      exposures based on satellite estimates for different age periods, and sun
      susceptibility in participants who had responded to two questionnaires (1994
      1998, 2003-2005) and who were cancer-free as of the earlier questionnaire. Using
      unconditional logistic regression, we estimated the odds ratio (OR) and 95%
      confidence intervals for 64,103 participants with 137 NHL cases. Self-reported
      time outdoors in summer was unrelated to risk. Lower risk was somewhat related to
      higher average year-round and winter ambient exposure for the period closest in
      time, and prior to, diagnosis (ages 20-39). Relative to 1.0 for the lowest
      quartile of average year-round ambient UV, the estimated OR for successively
      higher quartiles was 0.68 (0.42-1.10); 0.82 (0.52-1.29); and 0.64 (0.40-1.03), p
      trend=0.06), for this age period. The lower NHL risk associated with higher year
      round average and winter ambient UV provides modest additional support for a
      protective relationship between UV and NHL.

PMID- 20826095
TI  - Predicting biopsy-proven prostate cancer recurrence following cryosurgery.
AB  - OBJECTIVES: Prostate cancer (CaP) cryosurgery utilizes PSA nadir level and
      radiotherapy criteria as surrogates for success. We attempted to correlate PSA
      doubling time (PSAdt) and time of undetectable PSA (TUPSA) with biopsy-proven
      cancer recurrence (BPR) in men treated with primary third-generation cryotherapy
      for clinically localized CaP. MATERIALS AND METHODS: Demographic, clinical, and
      pathologic data was retrieved including age, race, use of preoperative hormones
      or 5-alpha reductase inhibitors (5-ARIs), initial biopsy PSA, biopsy Gleason
      score, cT stage, prostate volume, presence/absence median lobe, and follow-up.
      Post-cryotherapy biopsy was considered for PSA levels >= 0.5 ng/ml. PSAdt was
      determined by the log-slope method. TUPSA was defined as time from surgery to a
      PSA value >= 0.2 ng/ml or most recent follow-up if undetectable. RESULTS: Ninety
      seven patients were identified. Preoperative hormonal manipulation was used in 25
      (26%); 5 (5%) were using a 5-ARI. Twenty-seven (29%) underwent post-cryotherapy
      biopsy, 12 (12%) had a BPR. In 41 (42%), PSAdt was calculated (median 11.9
      months, IQR 6.6-34.8); no significant difference between patients with BPR and
      without CaP was found (P = 0.46). TUPSA was a median of 4.9 months (IQR 3.2-9.9)
      vs. 15.6 months (IQR 6.1-30.3) for BPR or no CaP, respectively (P = 0.005). On
      proportional hazards regression, TUPSA was the only independent predictor of BPR
      (P = 0.03, OR 0.91). CONCLUSIONS: Post-cryosurgery PSAdt does not appear to be
      associated with BPR risk, whereas TUPSA reduces the risk of BPR by 9% per month.
      This may help guide management if local failure is suspected.

PMID- 20826096
TI  - Ultrasonographic examination of the small intestine, large intestine and greater
      omentum in 30 Saanen goats.
AB  - The small and large intestine of 30 healthy Saanen goats were examined
      ultrasonographically using a 5.0 MHz-linear transducer. The goats were examined
      on the right side, from the eighth rib to the caudal aspect of the flank. The
      small and large intestine could be easily differentiated. The descending duodenum
      could be imaged in 19 goats, and the jejunum and ileum seen in all goats. The
      jejunum and ileum were most often seen in cross-section and rarely in
      longitudinal section in the ventral region of the right flank. The intestinal
      contents were usually homogenously echoic, and active motility was observed in
      all the goats. The diameter of the small intestine was 0.8-2.7 cm (1.6 [0.33]
      cm). The spiral ansa of the colon was imaged in all the goats, and in 21 the
      caecum was also seen. Both these sections of large intestine were most commonly
      seen in the dorsal region of the right flank. The spiral ansa of the colon was
      easily identified by its spiral arrangement of centripetal and centrifugal gyri,
      which had a garland-like appearance. Because of intraluminal gas, only the wall
      of the colon closest to the transducer could be imaged. The diameter of the
      spiral colon ranged from 0.8 to 2.0 cm (1.1 [0.24] cm). Usually only the wall of
      the caecum closest to the transducer could be imaged and it appeared as a thick,
      echoic, slightly undulating line. The greater omentum could be seen in all the
      goats.

PMID- 20826098
TI  - High antibody titer in an adult with Pompe disease affects treatment with
      alglucosidase alfa.
AB  - Clinical trials have demonstrated beneficial effects of enzyme replacement
      therapy (ERT) with alglucosidase alfa in infants, children and adults with Pompe
      disease. Recent studies have shown that high antibody titers can occur in
      patients receiving ERT and counteract the effect of treatment. This particularly
      occurs in those patients with classic-infantile Pompe disease that do not produce
      any endogenous acid alpha-glucosidase (CRIM-negative). It is still unclear to
      what extent antibody formation affects the outcome of ERT in adults with residual
      enzyme activity. We present the case of a patient with adult-onset Pompe disease.
      He was diagnosed at the age of 39years by enzymatic testing (10.7% residual
      activity in fibroblasts) and DNA analysis (genotype: c.-32-13T>G/p.Trp516X).
      Infusion-associated reactions occurred during ERT and the patient's disease
      progressed. Concurrently, the antibody titer rose to a similarly high level as
      reported for some CRIM-negative patients with classic-infantile Pompe disease.
      Using newly developed immunologic-assays we could calculate that approximately
      40% of the administered alglucosidase alfa was captured by circulating
      antibodies. Further, we could demonstrate that uptake of alglucosidase alfa by
      cultured fibroblasts was inhibited by admixture of the patient's serum. This case
      demonstrates that also patients with an appreciable amount of properly folded and
      catalytically active endogenous acid alpha-glucosidase can develop antibodies
      against alglucosidase alfa that affect the response to ERT.

PMID- 20826099
TI  - Overexpression of LYRM1 induces mitochondrial impairment in 3T3-L1 adipocytes.
AB  - Homo sapiens LYR motif containing 1 (LYRM1) is a recently discovered gene
      involved in adipose tissue homeostasis and obesity-associated insulin resistance.
      The exact mechanism by which LYRM1 induces insulin resistance has not yet been
      fully elucidated. In this study, we demonstrated that the overexpression of LYRM1
      in 3T3-L1 adipocytes resulted in reduced insulin-stimulated glucose uptake, an
      abnormal mitochondrial morphology, and a decrease in intracellular ATP synthesis
      and mitochondrial membrane potential. In addition, LYRM1 overexpression led to
      excessive production of intracellular of reactive oxygen species. Collectively,
      our results indicated that the overexpression of LYRM1 caused mitochondrial
      dysfunction in adipocytes, which might be responsible for the development of
      LYRM1-induced insulin resistance.

PMID- 20826100
TI  - ELMO1 variants and susceptibility to diabetic nephropathy in American Indians.
AB  - Variants in the engulfment and cell motility 1 gene, ELMO1, have previously been
      associated with kidney disease attributed to type 2 diabetes. The Pima Indians of
      Arizona have high rates of diabetic nephropathy, which is strongly dependent on
      genetic determinants; thus, we sought to investigate the role of ELMO1
      polymorphisms in mediating susceptibility to this disease in this population.
      Genotype distributions were compared among 141 individuals with nephropathy and
      416 individuals without heavy proteinuria in a family study of 257 sibships, and
      107 cases with diabetic ESRD and 108 controls with long duration diabetes and no
      nephropathy. We sequenced 17.4 kb of ELMO1 and identified 19 variants. We
      genotyped 12 markers, excluding those in 100% genotypic concordance with other
      variants or with a minor allele frequency <0.05, plus 21 additional markers
      showing association with ESRD in earlier studies. In the family study, the
      strongest evidence for association was with rs1345365 (odds ratio [OR]=2.42 per
      copy of A allele [1.35-4.32]; P=0.001) and rs10951509 (OR=2.42 per copy of A
      allele [1.31-4.48]; P=0.002), both of which are located in intron 13 and are in
      strong pairwise linkage disequilibrium (r(2)=0.97). These associations were in
      the opposite direction from those observed in African Americans, which suggests
      that the relationship between diabetic kidney disease and ELMO1 variation may
      involve as yet undiscovered functional variants or complex interactions with
      other biological variables.

PMID- 20826102
TI  - The incidence of atubular glomeruli in nephropathic cystinosis renal biopsies.
AB  - Nephropathic cystinosis results from lysosomal cystine storage and, if untreated
      with cysteamine, results in end-stage renal disease by 10 years of age. The renal
      Fanconi syndrome occurs in the first year of life and is accompanied by a
      characteristic "swan neck" deformity of the proximal renal tubule. The linkage
      between cystine storage, Fanconi syndrome, and renal failure has not been
      understood. This study reports the presence of substantial numbers of atubular
      glomeruli (ATG) in end-stage cystinotic renal tissue. Compared to normal renal
      tissue, cystinotic kidneys at end stage had 69% atubular glomeruli and 30%
      atrophic glomeruli. Normal renal tissue had 4% ATG and 0% atrophic glomeruli
      (p<0.0001 for both comparisons). These nonfunctioning nephrons may be the end
      result of cell loss from the tubules and represent the final stage of the swan
      neck deformity. The process is consistent with the previously reported increased
      apoptosis in renal tubule cells due to lysosomal cystine storage.

PMID- 20826101
TI  - Chemical chaperone therapy: luciferase assay for screening of beta-galactosidase
      mutations.
AB  - beta-Galactosidosis is a group of disorder based on heterogeneous mutations of
      GLB1 gene coding for the lysosomal acid beta-galactosidase (beta-gal). A decrease
      of the beta-gal enzyme activity results in progressive accumulation of substrates
      in somatic cells, particularly in neurons, leading to severe neuronal
      dysfunction. We have previously reported that N-octyl-4-epi-beta-valienamine
      (NOEV), a chemical chaperone compound, stabilized various mutant human beta-gal
      proteins and increased residual enzyme activities in cultured fibroblasts from
      human patients. These data proved a potential therapeutic benefit of chemical
      chaperone therapy for patients with missense beta-gal. This effect is mutation
      specific. In this study, we have established a sensitive luciferase-based assay
      for measuring chaperone effect on mutant human beta-gal. A dinoflagellate
      luciferase (Dluc) cDNA was introduced to the C-terminus of human beta-gal. When
      COS7 cells expressing the Dluc-tagged human R201C beta-gal was treated with NOEV,
      there happened a remarkable increase of the mutant beta-gal activity. In the
      presence of NH(4)Cl, luciferase level in the medium increased in parallel with
      the enzyme activity in cell lysates. We also found that proteasome inhibitors
      enhance chaperone effect of NOEV. These results demonstrate that the luciferase
      based assay is a reliable and convenient method for screening and evaluation of
      chaperone effects on human beta-gal mutants, and that it will be a useful tool
      for finding novel chaperone compounds in the future study.

PMID- 20826103
TI  - [Towards integrated care. Nursing assessment of a "complex" patient using
      intermed].
AB  - Nurses are confronted with an increasing number of patients with complex health
      care needs. INTERMED (INTERdisciplinary MEDicine) is described here as an action
      oriented method to document the potential "complexity" of patients, summarising
      information on biological, psychological, social and health care domains, plotted
      on a time-axis (history, current state and prognoses). A 73 year old patient
      assessed with this tool on admission to an internal medicine ward is described.
      INTERMED identified that besides age, mental health problems were interfering
      with somatic state and identified the patient as a complex case. From an integral
      health care perspective, coordinated care was needed to focus on the
      psychological vulnerability of the patient that made the somatic state more
      complex, including all the health care providers involved. Complex patients are
      an important and interesting issue for today's nurses, challenging their ability
      for management, organisation and coordination of care beyond standard care and
      the INTERMED tool can be crucial in this development.

PMID- 20826104
TI  - [Teoria fundamentada... is this a suitable translation for grounded theory?].

PMID- 20826105
TI  - [Clinical presentation, therapeutic approach and outcomes in acute poisoning
      treated with activated charcoal. Are there differences between men and women?].
AB  - OBJECTIVE: To determine whether there are gender-based differences in the
      clinical presentation, therapeutic approaches and outcomes in acute poisoning
      treated with activated charcoal. METHOD: A descriptive study conducted in the
      Emergency Department of the Hospital Clinic de Barcelona over the 7 years between
      the years 2001 and 2008. The study included poisoned patients who had received
      activated charcoal. The variables included, epidemiological data, clinical and
      toxicological presentation, therapeutic approach, time in emergency department
      and outcomes. RESULTS: A total of 575 patients were included in the study. The
      mean age was 37.8 (SD 14.8) years and 65.7% were females. No differences were
      observed between males and females with respect to age, number of drugs involved
      in the poisoning or the number of tablets ingested, but a higher prevalence of
      benzodiazepine poisoning was observed in females compared to males (69.8 vs.
      61.2%; P<0.05). Alcohol combined with drug poisoning was more common in males
      than in females (32.4 vs.18.8%; P<0.001). Administration of activated charcoal in
      non-drug poisoning was also more common in males than in females (7.9 vs. 3.2%;
      P<0.05). There were no differences between genders as regards clinical
      presentation of the poisonings, delays in care, hours of emergency department
      stay, treatment or outcome. CONCLUSIONS: Benzodiazepine poisoning was more
      prevalent in females than in males. Non-drug poisonings and alcohol combined with
      drug ingestion were more common in males. The clinical outcomes of the
      poisonings, delays in care, therapeutic requirements and admissions were similar
      between genders.

PMID- 20826106
TI  - [Knowledge, attitudes and barriers perceived by nurses to include scientific
      evidence into clinical practice in a university hospital].

PMID- 20826107
TI  - Ultrasound-enhanced one-pot synthesis of 3-(Het)arylmethyl-4-hydroxycoumarins in
      water.
AB  - 3-(Aryl)methyl-4-hydroxycoumarins were produced in good to excellent yields by
      reaction between 4-hydroxycoumarin and (hetero)aromatic aldehydes in the presence
      of Hantzsch 1,4-dihydropyridine (HEH) which works as an hydride donor (i.e., in a
      sequential Knoevenagel-reductive Michael addition). The sonochemical-assisted
      procedure (method B) provides an improved and accelerated conversion when
      compared to conventional silent reactions (method A). Experiments carried out
      according to method B showed that the reaction could be more efficiently run in
      the absence of organic solvents, at 30-40 degrees C in open vessel, without the
      need of an excess HEH and with simplified work-up and separation procedures.

PMID- 20826108
TI  - Degradation of reactive brilliant red K-2BP in aqueous solution using swirling
      jet-induced cavitation combined with H2O2.
AB  - The degradation of reactive brilliant red K-2BP (K-2BP) in aqueous solution by
      using swirling jet-induced cavitation, ultrasonic cavitation, and swirling jet
      induced cavitation combined with H(2)O(2), ultrasonic cavitation combined with
      H(2)O(2) was investigated. An obvious synergetic effect between hydrodynamic
      cavitation and H(2)O(2) was found and a variety of reaction parameters were
      investigated for the degradation of K-2BP. It was found that the degradation of K
      2BP by hydrodynamic cavitation combined with H(2)O(2) follows a pseudo-first
      order kinetics. Higher temperature of medium, higher-pressure of fluid and higher
      concentration of H(2)O(2) are favorable for the degradation of K-2BP, and lower
      medium pH, lower initial dye concentrations also favored K-2BP degradation. The
      degradation mechanism of reactive brilliant red K-2BP also discussed with the UV
      Vis spectra of the dye solution at different degradation time.

PMID- 20826110
TI  - The 5-12 Hz oscillations in the barrel cortex of awake rats--sustained attention
      during behavioral idling?
AB  - OBJECTIVE: 5-12 Hz oscillations, observed in cortical LFP of awake rats during
      quiet immobility, were proposed to be either (i) epileptic events or (ii)
      physiological alpha-like oscillations, manifesting an idling state of the cortex.
      We aimed to test this controversy. METHODS: We recorded LFP from the barrel
      cortex of awake Wistar rats, while applying weak tactile (whisker) and stronger
      arousing (electrical) stimuli. RESULTS: We observed a mean effect of
      desynchronization of the 5-12 Hz rhythm by the weak tactile stimulation. Arousal
      reduced the incidence of the 5-12 Hz oscillations and increased the
      desynchronizing power of tactile stimuli. CONCLUSIONS: Oscillations that can be
      disrupted by weak, purely tactile stimulation, and whose incidence is reduced by
      increased arousal, should be interpreted as a physiological phenomenon typical
      for behavioral idling while the cerebral cortex maintains sensory sensitivity.
      SIGNIFICANCE: Our results contradict the view that the 5-12 Hz oscillatory
      activity, often observed in fronto-parietal cortical regions of Wistar rats,
      represents epileptic discharges. Rather, this activity provides a model for
      studying the physiology of alpha/mu oscillations.

PMID- 20826109
TI  - Increased biomagnetic activity in healthy elderly with subjective memory
      complaints.
AB  - OBJECTIVE: Subjective memory complaints (SMCs) are frequently reported by elderly
      people with or without objective cognitive impairment (OMI) as assessed by
      neuropsychological tests. We investigate whether SMCs are associated with altered
      brain biomagnetic patterns even in the absence of OMI. METHODS: We report spatio
      temporal patterns of brain magnetic activity recorded with magnetoencephalography
      during a memory task in 51 elderly participants divided into the following
      groups: patients with mild cognitive impairment (MCI) with SMC and OMI,
      individuals with SMC but not OMI, and healthy controls without neither SMC nor
      OMI. Exclusion criteria for all three groups included a diagnosis of depression
      or any other psychiatric condition. RESULTS: No statistically significant
      differences were found between MCI patients and participants with SMC. However,
      the SMC showed higher activation, between 200 and 900 ms after stimulus onset,
      than the control group in posterior ventral regions and in the dorsal pathway.
      MCI patients showed higher activation than the control group in the posterior
      part of the ventral pathway. CONCLUSIONS: These findings suggest that similar
      physiological mechanisms may underlie SMC and MCI, which could be two stages in a
      cognitive continuum. SIGNIFICANCE: MEG provide different neurophysiological
      profiles between SMC and control subjects.

PMID- 20826111
TI  - High resolution event-related potentials analysis of the arithmetic-operation
      effect in mental arithmetic.
AB  - OBJECTIVE: Early, late and slow waves of event-related potentials (erps)
      appearing around 0-300 ms, 300-500 ms and after 500 ms respectively post-question
      presentation have been differentially associated to mental arithmetic processing
      (MAP). We hypothesized that arithmetic-operation effect (AOE) will show greater
      modulation of early components (P100, P200) in high-frequency erps; late
      components (P300, N300) and slow waves in low-frequency ERP when large-size
      problems are employed. METHODS: Fourteen normal human subjects mentally processed
      large- and small-size addition, division, multiplication and subtraction
      problems. Spatiotemporal differences between these arithmetic-operations were
      studied by way of comparing amplitudes and latencies of early, late and slow
      waves. RESULTS: All components were modulated by AOE. Modulated was observed as
      early as 100 ms post-question presentation (in high-frequency ERP components).
      AOE was very pronounced in large-size problems (in low-frequency ERP components).
      CONCLUSIONS: Results suggest that modulation by AOE of ERP components is improved
      when large-size problems and low-frequency ERP components are employed. Thus,
      differentiation of neuropsychological processes manifested by amplitude and
      latency of ERP components may be best studied by first separating components into
      high- and low-frequency erps. SIGNIFICANCE: Findings raise the potential of
      obtaining ERP indices that may improve findings about the degree (and time) of
      engagement of cognitive processes (e.g. Strategy employed in MAP).

PMID- 20826112
TI  - Engineering of protease-resistant phytase from Penicillium sp.: high thermal
      stability, low optimal temperature and pH.
AB  - Phytase is widely used as a feed additive in industry. It is important to
      investigate the thermal stability, optimal pH and temperature and protease
      resistance of phytases in application. We introduced random mutations in a
      protease-resistance phytase gene of Penicillium sp. using Mn2+-dITP random
      mutation method, and identified two mutants 2-28 (T11A, G56E, L65F, Q144H and
      L151S) and 2-249 (T11A, H37Y, G56E, L65F, Q144H, L151S and N354D) with improved
      thermal stability and optimal temperature and pH. The mutants retained their high
      resistance to pepsin. The catalytic activity at 37  degrees C was up to 133.3 U
      and 136.6 U per mg protein with broad optimal temperature ranges of 37-55 
      degrees C and 37-50  degrees C, respectively. After a heat treatment at 100 
      degrees C for 5 min, the two mutant proteins retained about 72.81% and 92.43% of
      the initial activity, respectively. In addition, the optimal pH of mutant 2-249
      was reduced to 4.8. All these improved properties made them more suitable to be
      used as feed additive in the feed industry than the present commercial phytases.
      Structure analysis suggested that the replacements of G56E, L65F, Q144H, and
      L151S improved the thermal stability of the protein by increasing new hydrogen
      bonds among the adjacent secondary structures. Moreover, the mutation of L151S
      enhanced the activity in the range of 37-70  degrees C and pH 2.5-7.0 by
      facilitating the interaction between the substrate and the catalytic centre. The
      substitution of N354D influenced the pH profile by weakening the bondage with the
      side chain of D353, which caused a pKa shift of the catalytic centre.

PMID- 20826113
TI  - Nurse-led telephone interventions for people with cardiac disease: the importance
      of the multi-disciplinary approach.

PMID- 20826114
TI  - Smoking patterns among Jordanian health professionals: a study about the
      impediments to tobacco control in Jordan.
AB  - BACKGROUND: Little is known about Arab health professionals' smoking practices.
      AIM: This is the first study to examine smoking practices among Arab health
      professionals. METHODS: Background: Little is known about Arab nurses and
      physicians' smoking patterns. AIM: This study aims to examine smoking patterns
      among Arab nurses and physicians. METHODS: A total of 918 nurses and physicians
      participated in this study. Data were collected using the Global Professional
      Health Survey. RESULTS: About 38.8% are current smokers. The smoking percentages
      for male nurses and male physicians were high (83.8%, 94.6% respectively)
      compared to female nurses and female physicians (16.2%, 5.4% respectively).
      Approximately 53.8% wanted to quit and 60.6% had made previous quit attempts that
      lasted for more than two days. About 64.1% believed that nurses and physicians
      who smoke were less likely to advise patients to stop smoking. The predictors of
      smoking were: age when tried first cigarettes OR=6.36, 95% CI=4.48, 9.04; father
      smokes OR=1.95, 95% CI=1.40, 2.72; mother smokes OR=1.99, 95% CI=1.18, 3.39;
      shift work OR=1.45, 95% CI=1.04, 2.03; and the interaction (gender and
      profession) OR=1.82, 95% CI=1.55, 2.14. DISCUSSION: Effective interventions often
      begin with and/or depend on nurses and physicians being committed to smoking
      cessation. Given the very high smoking rates among nurses and physicians a key
      priority must be to provide quit smoking programs and to enable them to become
      effective champions of smoking cessation nationwide.

PMID- 20826115
TI  - Re-innervation of smooth muscle that is transplanted to provide urethral
      sphincter augmentation.
AB  - A number of methods to augment the resistance of the outlet of the urinary
      bladder and to improve continence have been developed, including the artificial
      urinary sphincter and the placement of skeletal muscle around the urethra. It has
      been recently shown in a rabbit model that transplantation of smooth muscle
      around the proximal urethra reduces incontinence caused by internal sphincter
      deficiency. In the present work we have investigated the re-innervation of a peri
      urethral smooth muscle transplant, and whether re-innervating axons have an
      appropriate effect when they are stimulated. Detrusor muscle from the dome of the
      bladder was transplanted to encircle the proximal urethras of rats. Rats
      tolerated the surgery and transplantation without any signs of compromised
      health. At 8 weeks the new sphincter was intact and easily recognised. The
      transplant contracted in response to transmural stimulation (1-5Hz for up to
      5min) in a similar way to freshly removed detrusor strips. Contractions were
      graded with stimulus frequency, they peaked at about 10s and faded to a lower
      tension that was maintained. The amplitudes of sustained contractions of the
      transplants were reduced to about 10% by hyoscine and were almost abolished by
      tetrodotoxin. Histological examination revealed healthy, vascularised smooth
      muscle in the transplants, similar in appearance to freshly dissected detrusor.
      Re-innervation was confirmed immunohistochemically for transplanted detrusor
      muscle and transplants of dartos muscle. We conclude that smooth muscle
      transplanted to form a new sphincter around the urethra becomes functionally re
      innervated and has potential to be used for sphincter augmentation.

PMID- 20826116
TI  - [Lung abscess complicating bariatric surgery].

PMID- 20826117
TI  - [Loose anagen hair syndrome. Diagnostic use of the trichogram].

PMID- 20826118
TI  - [Calcium intake and bone mineral density in a group of Spanish school-children].
AB  - INTRODUCTION: There are limited data available on bone mass status in Spanish
      children and or whether the differences are associated with diet/hygiene habits
      or geographical variability. SUBJECTS AND METHODS: To determine this association
      a cross-sectional study was carried out in three different areas (northern,
      central and southern Spain) and included 1176 schoolchildren between 5 and 12
      years old, randomly selected from schools in those areas. Bone density of the
      distal phalanges was measured by bone ultrasound. We examine the correlations
      between these data and calcium and vitamin D intake, physical activity and bone
      mass index. RESULTS: Of the 1176 children initially included, 1035 nutritional
      questionnaires were completed and bone ultrasound data were obtained on 991 of
      them. Eighteen percent of girls and 13% of boys had a calcium intake below 800 mg
      per day. More than 70% of children have a daily vitamin D intake under 2.5 mcg.
      Age and exercise showed a direct linear relationship with bone mineral density,
      and an inverse one for overweight. CONCLUSIONS: Both high physical activity and
      high calcium intake were associated with a higher bone mineral density, while
      overweight showed the opposite effect. Diet habits and exercise must be
      considered the main strategies to prevent adult osteoporosis during childhood.

PMID- 20826119
TI  - [Niemann-Pick type C disease: From neonatal cholestasis to neurological
      degeneration. Different phenotypes].
AB  - INTRODUCTION: Niemann-Pick type C is a lysosomal storage disorder caused by a
      defect in intracellular trafficking of cholesterol. It is a rare disease, usually
      caused by mutations in NPC1 gene, but in some cases by mutations in NPC2 gene.
      Usually it is present in the paediatric age with a great variability of clinical
      manifestations. This disease leads to neurological degeneration with various age
      related symptoms. Transient neonatal cholestasis, the appearance of splenomegaly
      and/or hepatomegaly may occur years before the neurological symptoms. PATIENTS
      AND METHODS: We report 6 cases diagnosed in our unit in the last 20 years. We
      reviewed the clinical manifestations, neuroradiological findings (MRI) and
      molecular analysis of all of them. RESULTS: The disease began before 6 years of
      age and 5 cases had liver dysfunction and cholestasis in the neonatal period.
      Ascites was detected in 2 cases in prenatal period. Five cases have or had
      splenomegaly. Mutations in NPC1 gene were detected in all of them. CONCLUSIONS:
      It is important to understand this disease and the identification of early
      clinical symptoms to make an early diagnosis, leading to appropriate treatment
      and avoiding unnecessary tests. Moreover, it is important to suitably advise
      families and provide them with genetic counselling.

PMID- 20826120
TI  - Derivation, characterization, and gene expression profile of two new human ES
      cell lines from India.
AB  - Human embryonic stem cells (hESCs) offer new avenues for studying human
      development and disease progression in addition to their tremendous potential
      toward development of cell-replacement therapies for various cellular disorders.
      We have earlier reported the derivation and characterization of Relicell((r))
      hES1, the first fully characterized hESC line generated from the Indian
      subcontinent. Recent studies have demonstrated discrete differences among hESC
      lines, in terms of both their growth properties and their differentiation
      propensity. To address some of these issues in the context of hESC research in
      India, we have recently generated two new hESC lines: Relicell((r)) hES2 and
      Relicell((r))hES3. Both these cell lines were derived using a combinatorial
      approach of immunosurgery followed by mechanical surgery for inner cell mass
      isolation. The cell lines exhibit the usual hESC characteristics including their
      ability to differentiate both in vitro and in vivo to yield the three germinal
      layers. Whole genome microarray analysis of these cell lines was compared with
      Relicell((r))hES1 and it showed that approximately 9000 genes were expressed by
      these lines. As expected the expression pattern of these new cell lines bore
      close resemblance to that of Relicell((r))hES1. A majority of the pluripotency
      genes and the genes known to inhibit various differentiation pathways were also
      expressed by these cell lines. We also observed that each of these cell lines
      expressed a unique set of genes that are mutually exclusive from each other.
      These results represent the first detailed characterization of a set of hESC
      lines originating from India.

PMID- 20826121
TI  - Psychometric evaluation of the SinoNasal Outcome Test-16 for quality of life in
      chronic rhinosinusitis with nasal polyps.
AB  - OBJECTIVES: In chronic rhinosinusitis (CRS), SinoNasal Outcome Test-16 (SNOT-16)
      is a specific quality of life (QoL) questionnaire, validated in English and
      existing in a French translation. The present study assessed the psychometric
      characteristics of the French translation in nasal polyposis (NP). METHODS: The
      QoL of 40 NP patients was assessed before and after endoscopic ethmoidectomy,
      with the generic Study Short Form 36 (SF-36) and the specific SNOT-16
      questionnaires. RESULTS: SF-36 scores were improved 1 year postoperatively. The
      SNOT-16 Cronbach alpha coefficient was 0.81. In the preoperative course, SNOT-16
      scores correlated with the mental composite score ([MCS]: P = 0.034; rho = -0.36)
      and the role-physical ([RP]: P = 0.02; rho = -0.39), vitality ([VT]: P = 0.008;
      rho = -0.44) and role-emotional ([RE]: P = 0.035; rho = -0.36) dimensions of the
      SF-36. SNOT-16 scores were poorer in women (P = 0.03) and in case of aspirin
      intolerance (P = 0.044). SNOT-16 scores were significantly lower 1 year after
      surgery (P = 0.0017). CONCLUSION: The SNOT-16 seemed, in the present series, to
      be a reliable, valid and sensitive questionnaire. Validation on a larger series
      could enable its use in the French NP population to assess the precise
      effectiveness of therapeutic strategies.

PMID- 20826122
TI  - Writing an article for the European Annals of Otorhinolaryngology, Head and Neck
      Surgery: rights and responsibilities.
AB  - Based on a review of the literature published on medical writing, the authors
      discuss the rules to respect in terms of both structure and substance to
      facilitate publication of studies in the European Annals of Otorhinolaryngology,
      Head and Neck Surgery. The main errors leading to an article's being rejected are
      detailed and analyzed.

PMID- 20826123
TI  - How to diagnose and treat symptomatic anterior cervical osteophytes?
AB  - INTRODUCTION: Forestier disease, a cervical anterior form of diffuse idiopathic
      skeletal hyperostosis (DISH) is electively diagnosed in the elderly population.
      ENT symptoms are likely prevalent (dysphagia, and less frequently dysphonia,
      dyspnea, etc.), but diagnosis and the relation between symptoms and anterior
      longitudinal ligament ossification can be difficult to demonstrate. Starting from
      two clinical cases and a review of the literature, the authors propose a
      diagnostic and therapeutic course of action. MATERIALS AND METHODS: A typical
      description of Forestier disease is related based on the cases of two 80- and 79
      year-old men referred with gradually worsening swallowing problems leading to
      dysphagia. Both underwent surgical resection of cervical osteophytes via a
      lateral cervical approach after failure of the medical treatments. DISCUSSION:
      Based on the clinical presentations and the analysis of the literature, the
      authors describe the clinical features of the cervical anterior form of DISH
      presenting with ENT symptoms. The diagnosis and conservative therapeutic, and
      surgical management of anterior cervical hyperostosis based on ongoing gradual
      solutions are described.

PMID- 20826124
TI  - Dilatation of the vestibular aqueduct and lipiodol.

PMID- 20826125
TI  - Happy birthday cell penetrating peptides: already 20 years.
AB  - The recent discovery of new potent therapeutic molecules that do not reach the
      clinic due to poor delivery and low bioavailability has made of delivery a
      keystone in therapeutic development. Several technologies have been designed to
      improve cellular uptake of therapeutic molecules, including cell-penetrating
      peptides (CPPs). CPPs were discovered 20 years ago based on the potency of
      several proteins to enter cells. So far numerous CPPs have been described which
      can be grouped into two major classes, the first requiring chemical linkage with
      the drug for cellular internalization, the second involving formation of stable,
      non-covalent complexes with cargos. Nowadays, CPPs constitute as a very promising
      tool for non-invasive cellular import of cargos and have been successfully
      applied for ex vivo and in vivo delivery of therapeutic molecules varying from
      small chemical molecules, nucleic acids, proteins, peptides, liposomes to
      particles. This short introduction will highlight the major breakthroughs in the
      CPP history, which have driven these delivery agents to the clinic.

PMID- 20826126
TI  - A plausible mode of action of pseudin-2, an antimicrobial peptide from Pseudis
      paradoxa.
AB  - The search for new antibiotic agents is continuous, reflecting the continuous
      emergence of antibiotic-resistant pathogens. Among the new agents are the
      antimicrobial peptides (AMPs), which have the potential to become a leading
      alternative to conventional antibiotics. Studies for the mechanisms of action of
      the naturally occurring parent peptides can provide the structural and functional
      information needed for the development of effective new antibiotic agents. We
      therefore characterized pseudin-2, an AMP isolated from the skin of the South
      American paradoxical frog Pseudis paradoxa. We found that pseudin-2 organized to
      an aggregated state in aqueous solution, but that it dissociated into monomers
      upon binding to lipopolysaccharide (LPS), even though it did not neutralize LPS
      in Gram-negative bacteria. In addition, pseudin-2 assumed an alpha-helical
      structure in the presence of biological membranes and formed pores in both
      bacterial and fungal membranes, through which it entered the cytoplasm and
      tightly bound to RNA. Thus, the potent antimicrobial activity of pseudin-2 likely
      results from both the formation of pores capable of collapsing the membrane
      potential and releasing intracellular materials and its inhibition of
      macromolecule synthesis through its binding to RNA.

PMID- 20826127
TI  - Rb(+) occlusion stabilized by vanadate in gastric H(+)/K(+)-ATPase at 25 degrees
      C.
AB  - Despite its similarity with the Na(+)/K(+)-ATPase, it has not been possible so
      far to isolate a K(+)-occluded state in the H(+)/K(+)-ATPase at room temperature.
      We report here results on the time course of formation of a state containing
      occluded Rb(+) (as surrogate for K(+)) in H(+)/K(+)-ATPase from gastric vesicles
      at 25 degrees C. Alamethicin (a pore-forming peptide) showed to be a suitable
      agent to open vesicles, allowing a more efficient removal of Rb(+) ions from the
      intravesicular medium than C(12)E(8) (a non-ionic detergent). In the presence of
      vanadate and Mg(2+), the time course of [(86)Rb]Rb(+) uptake displayed a fast
      phase due to Rb(+) occlusion. The specific inhibitor of the H(+)/K(+)-ATPase
      SCH28080 significantly reduces the amount of Rb(+) occluded in the vanadate
      H(+)/K(+)-ATPase complex. Occluded Rb(+) varies with [Rb(+)] according to a
      hyperbolic function with K(0.5)=0.29+/-0.06mM. The complex between the Rb(+)
      occluded state and vanadate proved to be very stable even after removal of free
      Mg(2+) with EDTA. Our results yield a stoichiometry lower than one occluded Rb(+)
      per phosphorylation site, which might be explained assuming that, unlike for the
      Na(+)/K(+)-ATPase, Mg(2+)-vanadate is unable to recruit all the Rb(+)-bound to
      the Rb(+)-occluded form of the Rb(+)-vanadate-H(+)/K(+)-ATPase complex.

PMID- 20826128
TI  - Diagnostic value of glucose-6-phosphate isomerase in rheumatoid arthritis.
AB  - BACKGROUND: Although glucose-6-phosphate isomerase (G6PI), anti-G6PI antibodies
      and G6PI-containing immune complexes (G6PI-CIC) have proved high expression in
      patients with rheumatoid arthritis (RA), comprehensive evaluation of the G6PI
      derived markers, G6PI antigen, anti-G6PI Abs, G6PI-CIC and G6PI mRNA, in the
      diagnosis of RA remains necessary. METHODS: We measured G6PI antigen, anti-G6PI
      Abs, C1q/G6PI-CIC as well as anti-cyclic citrullinated peptide antibodies (anti
      CCP Abs) in serum and concomitantly synovial fluid (SF) by ELISA in RA, other
      rheumatic diseases and healthy controls. The G6PI mRNA expression in peripheral
      blood mononuclear cells (PBMCs) was assessed with real-time PCR. RESULTS: As
      compared with non-RA patients, RA patients had increased levels of G6PI antigen,
      anti-G6PI Abs, C1q/G6PI-CIC and G6PI mRNA expression in sera or PBMCs, and
      increased levels of G6PI and C1q/G6PI-CIC in SF. The serum G6PI levels in RA
      patients positively correlated with anti-G6PI Abs, C1q/G6PI-CIC, G6PI mRNA, anti
      CCP Abs, RF, CRP and ESR, respectively. The area under curve analyses
      demonstrated that serum G6PI had the best discriminating power for RA and active
      RA followed by C1q/G6PI-CIC, anti-G6PI Abs and G6PI mRNA. The simultaneous use of
      serum G6PI and anti-CCP Abs assays in the form of either of them tested positive
      gave improved sensitivities of 88.1% for RA and 95.8% for active RA. CONCLUSIONS:
      Despite the elevated expression of all G6PI-derived markers in RA, the serum G6PI
      has the best discriminating power among the four G6PI-derived markers. The serum
      G6PI determination either alone or in combination with anti-CCP Abs improves the
      diagnosis of RA.

PMID- 20826129
TI  - Cryopreservation and ultrasounds: why dig up the past?

PMID- 20826130
TI  - Categorical data analysis in experimental biology.
AB  - The categorical data set is an important data class in experimental biology and
      contains data separable into several mutually exclusive categories. Unlike
      measurement of a continuous variable, categorical data cannot be analyzed with
      methods such as the Student's t-test. Thus, these data require a different method
      of analysis to aid in interpretation. In this article, we will review issues
      related to categorical data, such as how to plot them in a graph, how to
      integrate results from different experiments, how to calculate the error
      bar/region, and how to perform significance tests. In addition, we illustrate
      analysis of categorical data using experimental results from developmental
      biology and virology studies.

PMID- 20826131
TI  - Sustained morphine treatment augments prostaglandin E2-evoked calcitonin gene
      related peptide release from primary sensory neurons in a PKA-dependent manner.
AB  - Tissue damage leads to pain sensitization due to peripheral and central release
      of excitatory mediators such as prostaglandin E2 (PGE2). PGE2 sensitizes spinal
      pain neurotransmitter such as calcitonin gene-related peptide (CGRP) release via
      activation of cyclic AMP (cAMP)/protein kinase A (PKA)-dependent signaling
      mechanisms. Our previous data demonstrate that sustained morphine pretreatment
      sensitizes adenylyl cyclase(s) (AC) toward the direct stimulator, forskolin, in
      cultured primary sensory neurons (AC superactivation). In the present work we
      investigated the hypothesis that morphine pretreatment also sensitizes ACs toward
      Gs-protein-coupled excitatory modulators (such as PGE2), leading to augmented PKA
      dependent CGRP release from PGE2-stimulated primary sensory dorsal root ganglion
      (DRG) neurons. Our results show that sustained morphine treatment potentiated
      PGE2-mediated cAMP formation and augmented PGE2-evoked CGRP release from cultured
      primary sensory neurons in a PKA-dependent manner. Our data suggest that
      attenuation of AC superactivation in primary sensory neurons may prevent the
      development of opioid-induced hyperalgesia.

PMID- 20826132
TI  - Metabotropic glutamate receptor mGlu2 is resistant to homologous agonist-induced
      desensitization but undergoes protein kinase C-mediated heterologous
      desensitization.
AB  - To investigate the susceptibility of the group II metabotropic glutamate receptor
      mGlu2 to agonist-induced desensitization, the receptor was stably expressed in
      Chinese hamster ovary (CHO-mGlu2) or C6 glioma cells (C6-mGlu2). Exposure of CHO
      mGlu2 cells to the group II mGlu receptor agonist (2S,1'S,2'S)-2
      (carboxycyclopropyl)glycine (LCCG-1; 10 MUM) for up to 15 h did not affect the
      subsequent ability of LCCG-1 to inhibit forskolin-stimulated cAMP accumulation.
      Similarly, in C6-mGlu2 cells, prolonged exposure to LCCG-1 also did not affect
      the subsequent ability of LCCG-1 to inhibit cAMP formation. In contrast, exposure
      of CHO-mGlu2 cells to the protein kinase C activator phorbol myristate acetate
      (PMA) suppressed the ability of LCCG-1 to inhibit cAMP formation. Using an in
      vitro model of group II mGlu receptor activity, the hemisected neonatal rat
      spinal cord preparation, the ability of the selective group II agonist (2R,4R)-4
      aminopyrrolidine-2,4-dicarboxylate ((2R,4R)-APDC) to depress the fast component
      of the dorsal root-evoked ventral root potential (fDR-VRP) did not desensitize
      when applied for up to 2 h. Together these results indicate that in contrast to
      most G protein-coupled receptors, the mGlu2 receptor is resistant to agonist
      induced homologous desensitization, and that in vitro data suggests that
      resistance to desensitization is a physiologically relevant property of this mGlu
      receptor subtype.

PMID- 20826133
TI  - Activity of a new hydrogen sulfide-releasing aspirin (ACS14) on pathological
      cardiovascular alterations induced by glutathione depletion in rats.
AB  - We investigated the effects of the hydrogen sulfide (H2S)-releasing derivatives
      of aspirin (ACS14) and salicylic acid (ACS21) in a rat model of metabolic
      syndrome induced by glutathione (GSH) depletion, causing hypertension and other
      pathological cardiovascular alterations. GSH depletion was induced in normal rats
      by the GSH-synthase inhibitor buthionine sulfoximine (BSO, 30 mmol/L day for
      seven days in the drinking water). Systolic blood pressure and heart rate were
      measured daily by the tail-cuff method, and plasma thromboxane B2, 6-keto
      prostaglandin F(2alpha), 8-isoprostane, GSH, insulin and glucose were determined
      at the end of the seven-day BSO schedule. In addition, ischemia/reperfusion
      induced myocardial dysfunction and endothelial dysfunction were assayed on
      isolated heart and aortic rings, respectively. Unlike aspirin and salicylic acid,
      ACS14 and ACS21 reduced BSO-induced hypertension, also lowering plasma levels of
      thromboxane B2, 8-isoprostane and insulin, while GSH remained in the control
      range. Neither ACS14 nor ACS21 caused gastric lesions. Both restored the
      endothelial dysfunction observed in aortic rings from BSO-treated rats, and in
      ischemia/reperfusion experiments they lowered left ventricular end-diastolic
      pressure, consequently improving the developed pressure and the maximum rise and
      fall of left ventricular pressure. Together with this improvement of heart
      mechanics there were reductions in the activity of creatine kinase and lactate
      dehydrogenase in the cardiac perfusate. This implies that H2S released by both
      ACS14 and ACS21 was involved in protecting the heart from ischemia/reperfusion,
      and significantly limited vascular endothelial dysfunction in aortic tissue and
      the related hypertension.

PMID- 20826134
TI  - Chronic lithium treatment protects the rat kidney against ischemia/reperfusion
      injury: the role of nitric oxide and cyclooxygenase pathways.
AB  - Ischemia/reperfusion injury is a major problem in renal transplantation. Several
      evidences represent lithium preconditioning effect against ischemia/reperfusion
      injury in various tissues. In this study our aim was to investigate the
      protective effect of chronic lithium administration on renal ischemia/reperfusion
      injury in rats. Ischemia/reperfusion injury was induced by clamping left renal
      pedicle for 60 min, 2 weeks after right nephrectomy. Lithium-treated animals
      received lithium-chloride in drinking water for 30days. In order to investigate
      the role of nitric oxide (NO) and cyclooxygenase (COX) pathways in renoprotective
      effect of lithium, N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME,
      NO synthase inhibitor) and indomethacin (COX inhibitor) were used, respectively.
      Serum creatinine, blood urea nitrogen and renal histology were assessed 24h after
      inducing ischemia/reperfusion injury. Dimercaptosuccinic acid scan was also
      performed 48 h following operation. Chronic lithium treatment in
      ischemia/reperfusion injury groups significantly decreased creatinine (1.09+/
      0.16 mg/dl), blood urea nitrogen (59.0+/-13.38 mg/dl), histological damage
      (7.83%+/-4.02%) and improved cortical function compared with non-lithium treated
      animals (4.45+/-0.44, 176.66+/-12.24 mg/dl and 83.5%+/-3.5%, respectively)
      (P<0.001). Either L-NAME or indomethacin administration partially reversed the
      protective effect of lithium, while simultaneous blockade of NO and COX pathways
      completely abolished lithium renoprotective effect. Our results indicate that
      lithium ameliorates renal ischemia/reperfusion injury through NO and/or COX
      pathways. We propose that lithium pre-treatment as a simple and practical
      intervention to boost the renal viability and function after ischemia/reperfusion
      injury may be promising in the setting of transplantation.

PMID- 20826135
TI  - Irbesartan enhances GLUT4 translocation and glucose transport in skeletal muscle
      cells.
AB  - Irbesartan, an angiotensin II type 1 receptor blocker has been reported to
      alleviate metabolic disorder in animal studies and human clinical trials.
      Although this effect may be related to the ability of irbesartan to serve as a
      partial agonist for the peroxisome proliferator-activated receptor (PPAR)-gamma,
      the target tissues on which irbesartan acts remain poorly defined. As muscle
      glucose transport plays a major role in maintaining systemic glucose homeostasis,
      we investigated the effect of irbesartan on glucose uptake in skeletal muscle
      cells. In C2C12 myotubes, 24-h treatment with irbesartan significantly promoted
      both basal and insulin-stimulated glucose transport. In L6-GLUT4myc myoblasts,
      irbesartan caused a significant increase in glucose transport and GLUT4
      translocation to the cell surface in a concentration-dependent manner. Valsartan,
      another angiotensin II type 1 receptor blocker had no effect on either glucose
      uptake or GLUT4 translocation, implying that these actions on glucose transport
      are independent of angiotensin II receptor blockade. Moreover, irbesartan exerted
      these effects in an additive manner with insulin, but not with acute treatment
      for 3 h, suggesting that they may require the synthesis of new proteins. Finally,
      in insulin-resistant Zucker fatty rat, irbesartan (50 mg/kg/day for 3 weeks)
      significantly ameliorated insulin resistance without increasing weight gain. We
      conclude that irbesartan has a direct action, which can be additive to insulin,
      of promoting glucose transport in skeletal muscle. This may be beneficial for
      ameliorating obesity-related glucose homeostasis derangement.

PMID- 20826136
TI  - Effects of reboxetine and citalopram pretreatment on changes in cocaine and
      amphetamine regulated transcript (CART) expression in rat brain induced by the
      forced swimming test.
AB  - Cocaine and amphetamine regulated transcript (CART) has been implicated in the
      regulation of the stress response. Although the forced swimming test (FST), in
      which rats are forced to swim for 15 min (pretest swim) and then again for 5 min
      (test swim) 24 h later, has been used to study the effects of antidepressants,
      there have been few studies examining the effects of antidepressants on FST
      induced changes in CART mRNA levels in the brain. To answer this question, we
      injected reboxetine and citalopram into male Sprague-Dawley rats 1, 5, and 23.5 h
      before the test swim and then sacrificed rats 2 h after the test swim, at the
      peak of the FST-induced increase in CART expression. The FST significantly
      increased CART mRNA levels in the nucleus accumbens, central nucleus of the
      amygdala, and locus ceruleus 2 h after the test session. Both reboxetine and
      citalopram pretreatment blocked FST-induced increases in CART mRNA levels in the
      nucleus accumbens, central nucleus of the amygdala, and locus ceruleus, despite
      the fact these antidepressants exert their therapeutic effect by different
      mechanisms. In addition, the FST significantly increased plasma corticosterone
      levels, and this effect was also blocked by reboxetine and citalopram
      pretreatment. These results suggest that inhibition of FST-induced increases in
      CART expression in the nucleus accumbens, central nucleus of the amygdala, and
      locus ceruleus may be a common mechanism of antidepressant effects during the
      FST.

PMID- 20826137
TI  - Genetic deletion of pleiotrophin leads to disruption of spinal nociceptive
      transmission: evidence for pleiotrophin modulation of morphine-induced analgesia.
AB  - Pleiotrophin (PTN) is a growth factor that exhibits neurotrophic actions and is
      upregulated at sites of nerve injury. Upregulation of PTN levels in injured
      dorsal root ganglion correlates with decreased mechanical allodynia and faster
      recovery from Chronic Constriction Injury of the rat sciatic nerve. Despite the
      evidence pointing to a role of PTN in the development of chronic pain, the role
      of this neurotrophic factor in pain transmission has not been assessed in acute
      pain models. We have now studied the behaviour of PTN genetically deficient (PTN
      /-) and wild type (PTN+/+) mice in the hot-plate and tail-immersion tests. We
      found that basal central pain responses do not differ between PTN-/- and PTN+/+
      mice in the hot-plate test. Very interestingly, basal latencies to a tail flick
      were significantly increased in PTN-/- mice as assessed in the tail-immersion
      test. It was also aimed to evaluate morphine-induced analgesia in PTN-/- and
      PTN+/+ mice. We did not find differences among genotypes using a high dose of
      morphine (10 mg/kg) in the hot-plate test, reaching this dose the analgesia peak
      25 min after injection (i.p.) and returning to almost basal values 125 min after
      injection. In contrast, we found that an intermediate dose of morphine (5 mg/kg)
      significantly delayed pain responses in PTN-/- mice compared to PTN+/+ mice in
      both the hot-plate and tail-immersion tests. The data strongly suggest that PTN
      is of critical importance for pain processing at the spinal level and,
      furthermore, that endogenous PTN modulates morphine-induced analgesic effects in
      mice.

PMID- 20826138
TI  - Presence and functional role of the rapidly activating delayed rectifier K(+)
      current in left and right atria of adult mice.
AB  - Repolarization of cardiac action potentials is regulated by several types of K(+)
      currents. The present study examined the presence and functional significance of
      rapid delayed rectifier (I(Kr)) in left and right atrial myocytes of mouse heart,
      using whole-cell patch-clamp method. The functional role of ultrarapid delayed
      rectifier (I(Kur)) in the repolarization was also examined by blocking with 4
      aminopyridine (50 MUM). The presence of I(Kr) was detected in left and right
      atrial myocytes as an E-4031 (5 MUM)-sensitive current that exhibited relatively
      rapid activation during depolarization and half activation voltage of -17.5 and 
      17.4 mV for left and right atrial myocytes, respectively. The current density of
      I(Kr) was similar between left and right atria. The prolongation of action
      potential measured at 50% repolarization evoked by 4-aminopyridine was
      significantly larger in left than in right atrium, which appears to be consistent
      with the larger amplitude of I(Kur) in left atrium. On the other hand, the
      prolongation of action potential measured at 90% repolarization caused by E-4031
      was significantly larger in right than in left atrium. The longer action
      potential of right atrium, which may result at least partly from smaller
      amplitude of I(Kur), is likely to enhance the functional significance of I(Kr) in
      repolarization process of right atrium, despite of similar magnitude of I(Kr) in
      left and right atria. Our data thus identifies I(Kr) in mouse atria and indicates
      the presence of functional interaction between I(Kr) and I(Kur) that potentially
      contributes to repolarization heterogeneity in left and right atria of mouse
      heart.

PMID- 20826139
TI  - Evaluation of loganin, iridoid glycoside from Corni Fructus, on hepatic and renal
      glucolipotoxicity and inflammation in type 2 diabetic db/db mice.
AB  - Previously, we have reported that Corni Fructus possessed hypoglycemic and
      hypocholesterolemic effects in streptozotocin-induced type 1 diabetic rats and
      diet-induced hypercholesterolemic rats. Herein, we have focused on the effect and
      mechanism of loganin, a major iridoid glycoside of Corni Fructus, on the type 2
      diabetic db/db mice. Loganin was orally administered to db/db mice at a dose of
      20 or 100 mg/kg body weight daily for 8 weeks. The biochemical factors and
      expressions of protein and mRNA related to lipid metabolism, inflammation,
      advanced glycation endproducts, and its receptor were measured. In loganin
      treated db/db mice, hyperglycemia and dyslipidemia were ameliorated in both the
      serum and hepatic tissue; however, in the kidney, only triglyceride was reduced.
      The enhanced oxidative stress was alleviated by loganin through a decrease in
      thiobarbituric acid-reactive substances (liver and kidney) and reactive oxygen
      species (serum, liver, and kidney), as well as augmentation of the oxidized to
      reduced glutathione ratio (liver and kidney). The marked lipid-regulatory effect
      of loganin was exerted in the liver of type 2 diabetic mice via suppressing mRNA
      expressions related to lipid synthesis and adjusting the abnormal expression of
      peroxisome proliferator-activated receptor alpha and sterol regulatory-element
      binding protein in the nucleus. Furthermore, loganin inhibited advanced glycation
      endproduct formation and the expression of its receptor, and nuclear factor-kappa
      B-induced inflammation in the hepatic tissue of db/db mice. Loganin exhibits
      protective effects against hepatic injury and other diabetic complications
      associated with abnormal metabolic states and inflammation caused by oxidative
      stress and advanced glycation endproduct formation.

PMID- 20826140
TI  - Effects of three N-(carboxyanilinomethyl) derivatives of p
      isopropoxyphenylsuccinimide on the anticonvulsant action of carbamazepine,
      phenobarbital, phenytoin and valproate in the mouse maximal electroshock-induced
      seizure model.
AB  - The aim of the study was to determine the influence of N-(ortho
      carboxyanilinomethyl)-p-isopropoxyphenylsuccinimide [o-CAMIPPS], N-(meta
      carboxyanilinomethyl)-p-isopropoxyphenylsuccinimide [m-CAMIPPS], and N-(para
      carboxyanilinomethyl)-p-isopropoxyphenylsuccinimide [p-CAMIPPS] on the protective
      activity of four classical antiepileptic drugs (carbamazepine, phenobarbital,
      phenytoin and valproate) in the mouse maximal electroshock seizure model. The
      results indicate that all tested succinimide derivatives administered
      intraperitoneally at doses of 75 and 150 mg/kg significantly elevated the
      threshold for electroconvulsions in mice. Succinimide derivatives at a dose of
      37.5 mg/kg had no effect on the threshold for electroconvulsions in mice.
      Furthermore, o-CAMIPPS (37.5 mg/kg) significantly reduced the anticonvulsant
      activity of carbamazepine, but not that of phenobarbital, phenytoin and valproate
      in the maximal electroshock-induced seizures in mice. Anticonvulsant efficacy of
      carbamazepine, phenobarbital, phenytoin and valproate in the maximal electroshock
      induced seizures in mice was not changed after administration of m-CAMIPPS or p
      CAMIPPS. Pharmacokinetic experiment revealed that o-CAMIPPS significantly
      increased total brain concentrations of carbamazepine in mice. In conclusion, the
      reduced anticonvulsant action of carbamazepine by o-CAMIPPS in the maximal
      electroshock-induced seizures, despite the increased total brain carbamazepine
      concentrations after combined administration of carbamazepine with o-CAMIPPS, may
      suggest the antagonistic interaction between drugs. The combinations of m-CAMIPPS
      or p-CAMIPPS with carbamazepine, phenobarbital, phenytoin and valproate were
      neutral from a preclinical viewpoint.

PMID- 20826141
TI  - The improvement of the anti-hyperalgesic effect of ketamine and of its isomers by
      the administration of ifenprodil.
AB  - Intrathecal or epidural administration of NMDA (N-methyl-D-aspartate) receptors
      antagonists, in special ketamine and ifenprodil are used to control moderate to
      severe hyperalgesia in humans. Activation of NMDA receptor usually requires
      binding of two agonists, glutamate and glycine, in different receptor subunits.
      Ketamine is a NMDA receptor antagonist and acts at phencyclidine site in NR1
      subunit while ifenprodil is a selective NR2B subunit antagonist of NMDA receptor.
      The aim of this study was to investigate the pharmacological interactions between
      ketamine or its isomers and ifenprodil, when intrathecally co-administrated, to
      reduce prostaglandin E(2)-induced hyperalgesia in rat's hind paw. The intrathecal
      administration of ketamine, its isomers R(-) or S(+), or ifenprodil-induced anti
      hyperalgesic effects in a dose-related manner. Ifenprodil, in a dose that did not
      induce significant effect when administrated alone, significantly improved the
      anti-hyperalgesic effect of ketamine or its isomers. The other way round,
      ketamine or S(+) ketamine, but not R(-) ketamine, in a dose that did not induce
      significant effect when administrated alone, improved the anti-hyperalgesic
      effect of ifenprodil. However, by comparing ED(50)s (half maximal effective
      doses), ifenprodil-induced potentiation of ketamine was significantly greater
      than ketamine-induced potentiation of ifenprodil. The findings of this present
      study suggest that intrathecal administration of very small doses of ifenprodil,
      just before and ketamine significantly improves its anti-hyperalgesic effect and
      this association could be useful to control inflammatory pain with less
      undesirable effects.

PMID- 20826142
TI  - Cornel iridoid glycoside improves memory ability and promotes neuronal survival
      in fimbria-fornix transected rats.
AB  - Cornel iridoid glycoside (CIG) is a main component extracted from a traditional
      Chinese herb Cornus officinalis. Our previous study found that CIG improved
      neurological function in cerebral ischemic rats. The aim of this study was to
      investigate the therapeutic benefit of CIG in rats with fimbria-fornix
      transection (FFT) and explore the underlying molecular mechanisms. CIG (20, 60
      and 180 mg/kg) or vehicle was intragastrically administered once daily to rats,
      starting immediately after the surgery and lasting for 4 weeks. Morris water maze
      and step-through tests showed that the memory deficits seen in FFT rats were
      significantly improved by CIG treatment. Immunohistochemical analysis showed that
      CIG treatment attenuated the loss of neurons in hippocampus. To elucidate the
      memory-improving mechanism of CIG, the neurotrophic factors, synaptic proteins
      and Bcl-2 family proteins in hippocampus were measured by Western blot analysis.
      FFT reduced hippocampal protein levels of nerve growth factor (NGF), tyrosine
      receptor kinase A (Trk A), brain-derived neurotrophic factor (BDNF),
      synaptophysin (SYP) and B-cell lymphoma-2 (Bcl-2), but not levels of tyrosine
      receptor kinase B (Trk B) and growth-associated protein 43 (GAP-43). FFT also
      elevated cytochorome C (Cyt c) and bcl-2-associated X protein (Bax).
      Administration of CIG to FFT rats significantly elevated the expression of NGF,
      TrkA, BDNF, SYP, GAP-43 and Bcl-2, and decreased the expression of Cyt c and Bax.
      These results indicated that CIG effectively counteracted cognitive impairments
      caused by fimbria-fornix lesions, and the mechanisms might be related to
      promoting neuronal survival and providing a beneficial environment for brain
      repair.

PMID- 20826143
TI  - Phorbol 12-myristate 13-acetate inhibits the antilipolytic action of insulin,
      probably via the activity of protein kinase Cepsilon.
AB  - Protein kinase CbetaI (PKCbetaI) mediates insulin signaling and attenuates beta1
      adrenoceptor-stimulated lipolysis. In this work, the effect of the PKC activator
      phorbol 12-myristate 13-acetate (PMA) on the antilipolytic action of insulin was
      determined by analyzing lipolysis induced by a beta3-adrenoceptor agonist CL
      316243. PMA inhibited the insulin antilipolytic action. The pan-PKC inhibitors GF
      109203X and chelerythrine inhibited the PMA effect, but the PKCalpha/beta
      inhibitors Go 6976 and CGP 53353 did not. Exposure of cells to PMA downregulated
      PKCs alpha, betaI, and delta within 3 h and PKCepsilon within 12 h. The effect of
      PMA on insulin action greatly diminished when PKCepsilon was downregulated.
      Inhibitors of phosphatidylinositol 3-kinase (PI3-K), Akt, and phosphodiesterase
      3B (PDE3B) diminished the PMA effect. PMA inhibited insulin-stimulated
      phosphorylation of Tyr in insulin receptor beta subunit and Ser/Thr in Akt. These
      data suggest that PMA inhibits the antilipolytic signal mediated by the insulin
      receptor, PI3-K, Akt, and PDE3B. The most probable target of PMA is PKCepsilon.

PMID- 20826144
TI  - Tanshinone IIA protects the human blood-brain barrier model from leukocyte
      associated hypoxia-reoxygenation injury.
AB  - To investigate the in vitro effect of tanshinone IIA on leukocyte-associated
      hypoxia-reoxygenation injury of human brain-blood barrier (BBB), we established
      the BBB model by culturing purified primary human brain microvascular endothelial
      cells (HBMVEC) to confluence on cell culture insert. BBB was identified by tight
      junction, transendothelial electrical resistance (TEER) and the permeability of
      BBB to horseradish peroxidase (HRP). The effect of tanshinone IIA on the
      permeability of BBB was tested at 2 h after hypoxia and 1h after reoxygenation
      with or without the supernatants of activated leukocytes. The effect of
      tanshinone IIA on leukocytes activation was analyzed by detection of MMP-9,
      cytokines and reactive oxygen species. The results showed that BBB formed by
      confluent HBMVECs had no cellular gap. Immunofluorescent staining for ZO-1
      confirmed that the cells were connected by tight junction. Moreover, the BBB
      model had a higher TEER and a lower permeability for HRP than confluent HUVECs.
      The permeability of BBB for HRP was enhanced by hypoxia-reoxygenation and further
      greatly enhanced by adding the supernatants of activated leukocytes before
      reoxygenation. But such an effect was reversed by addition of tanshinone IIA
      before hypoxia. Moreover, tanshinone IIA could decrease the levels of MMP-9, TNF
      alpha, IL-1alpha, IL-2, IFN-gamma and reactive oxygen species in leukocytes. In
      conclusion, tanshinone IIA can protect BBB against leukocyte-associated hypoxia
      reoxygenation injury by attenuating the activation of leukocytes and inhibiting
      the injury effects of leukocytic products. Tanshinone IIA may be a novel
      therapeutic agent for cerebral ischemia-reperfusion injury.

PMID- 20826146
TI  - Antinociceptive activity of a synthetic chalcone, flavokawin B on chemical and
      thermal models of nociception in mice.
AB  - The present study examined the potential antinociceptive activity of flavokawin B
      (6'-hydroxy-2',4'-dimethoxychalcone), a synthetic chalcone using chemical- and
      thermal-induced nociception models in mice. It was demonstrated that flavokawin B
      (FKB; 0.3, 1, 3 and 10 mg/kg) administered via both oral (p.o.) and
      intraperitoneal (i.p.) routes produced significant and dose-dependent inhibition
      in the abdominal constrictions induced by acetic acid, with the i.p. route
      producing antinociception of approximately 7-fold more potent than the p.o.
      route. It was also demonstrated that FKB produced significant inhibition in the
      two phases of the formalin-induced paw licking test. In addition, the same
      treatment of flavokawin B (FKB) exhibited significant inhibition of the
      neurogenic nociceptive induced by intraplantar injections of glutamate and
      capsaicin. Likewise, this compound also induced a significant increase in the
      response latency period to thermal stimuli in the hot plate test and its
      antinociceptive effect was not related to muscle relaxant or sedative action.
      Moreover, the antinociception effect of the FKB in the formalin-induced paw
      licking test and the hot plate test was not affected by pretreatment of non
      selective opioid receptor antagonist, naloxone. The present results indicate that
      FKB produced pronounced antinociception effect against both chemical and thermal
      models of pain in mice that exhibited both peripheral and central analgesic
      activity.

PMID- 20826145
TI  - Effects of formoterol and ipratropium bromide on repeated cadmium inhalation
      induced pulmonary inflammation and emphysema in rats.
AB  - The anti-inflammatory properties of inhaled formoterol and ipratropium bromide,
      alone or in combination, were investigated in a rat model of chronic pulmonary
      inflammation with airspace enlargement induced by cadmium inhalation. At the end
      of the protocol, cadmium-induced increase of airway resistance was prevented by
      formoterol (4 mg/30 ml) or ipratropium (0.20 mg/20 ml). Formoterol elicited a
      significant decrease in total cell and neutrophil counts in bronchoalveolar
      lavage fluid as well as on the activity of gelatinase B (MMP-9), an enzyme
      strongly expressed in alveolar macrophages and epithelial cells. Additionally, a
      significant attenuation of the lung lesions characterized by inflammatory cell
      infiltration within the alveoli and the interstitium and a decrease in mean
      linear intercept were observed. Although ipratropium alone had no effects on the
      cadmium-induced pulmonary inflammation and emphysema, its combination with an
      inefficient concentration of formoterol (1 mg/30 ml) showed a synergistic
      inhibitory effect on neutrophil and total cell counts as well as on the mean
      linear intercept associated with a synergistic inhibition on the MMP-9 activity.
      Gelatinase A (MMP-2) activity was not influenced by drug pretreatments. Neither
      macrophage metalloelastase (MMP-12) activity nor levels of cytokines IL-1beta,
      TNF-alpha and GM-CSF in bronchoalveolar lavage fluid were modified in rats
      chronically exposed to cadmium. No desensitization of beta(2)-adrenoceptors or
      cholinergic receptors on airway smooth muscles and inflammatory cells during the
      protocol was observed. In conclusion, formoterol alone or combined with
      ipratropium bromide partially protects the lungs against the chronic inflammation
      and airspace enlargement by reducing neutrophilic infiltration possibly via the
      inhibition of MMP-9 activity.

PMID- 20826147
TI  - 4'-chlorodiazepam--agonist of peripheral benzodiazepine receptors as a protecting
      factor in IL-1 induced deregulation of collagen biosynthesis in cultured human
      chondrocytes.
AB  - Degenerative joint diseases are related to the excessive degradation of collagen
      and proteoglycans in cartilage. One of the potent inflammatory mediators of
      cartilage metabolism is interleukin-1 (IL-1) that has been implicated in the
      pathogenesis of degenerative joint diseases. Peripheral benzodiazepine receptor
      ligands have anti-inflammatory activity in rheumatoid arthritis. The present
      study shows that 4'-chlorodiazepam (Ro-54864), an agonist of peripheral
      benzodiazepine receptors, counteract inhibition of collagen and DNA biosynthesis,
      induced by IL-1. Pk-1195, an antagonist of peripheral benzodiazepine receptors
      did not restore inhibitory effects of IL-1. The mechanism of collagen
      biosynthesis and cell division regulation involves insulin-like growth factor-I
      receptor signaling. We found that IL-1 inhibited expression of IGF-IR, while Ro
      54864 stimulated the expression of this receptor. Increase in the expression of
      this receptor was accompanied by increase in mTOR expression and AKT
      phosphorylation while it had no effect on Ras-Raf-mitogen activated protein
      kinase (MAPK) pathway. Although IL-1 caused activation of apoptosis in
      chondrocytes, an addition of Ro-54864 to the cells inhibited the process as
      detected by annexin V cell staining followed by flow cytometry. The mechanism of
      this process may be related to protective effect of signal induced by IGF-I
      receptor. The data suggest that the mechanism of the protective effects of Ro
      54864 on IL-1-induced effects in chondrocytes undergoes through mTOR and AKT
      signaling. It suggest that peripheral benzodiazepine receptor agonist may be
      considered as a potential pharmacotherapeutical agents in the treatment of
      inflammatory diseases.

PMID- 20826148
TI  - Potentiation of omega-3 fatty acid antidepressant-like effects with low non
      antidepressant doses of fluoxetine and mirtazapine.
AB  - Despite the advances in psychopharmacology, the treatment of depressive disorders
      is still not satisfactory. Side effects and resistance to antidepressant drugs
      are the greatest complications during treatment. Based on recent evidence, omega
      3 fatty acids may influence vulnerability and outcome in depressive disorders.
      The aim of this study was to further characterize the omega-3 antidepressant-like
      effect in rats in terms of its behavioral features in the depression model forced
      swimming test either alone or in combination with antidepressants fluoxetine or
      mirtazapine. Ultimately, we prompted to determine the lowest dose at which omega
      3 fatty acids and antidepressant drugs may still represent a pharmacological
      advantage when employed in combined treatments. Chronic diet supplementation with
      omega-3 fatty acids produced concentration-dependent antidepressant-like effects
      in the forced swimming test displaying a behavioral profile similar to fluoxetine
      but different from mirtazapine. Fluoxetine or mirtazapine at antidepressant doses
      (10 and 20 mg/kg/day, respectively) rendered additive effects in combination with
      omega-3 fatty acid supplementation (720 mg/kg/day). Beneficial effects of
      combined treatment were also observed at sub-effective doses (1 mg/kg/day) of
      fluoxetine or mirtazapine, since in combination with omega-3 fatty acids (720
      mg/kg/day), antidepressants potentiated omega-3 antidepressant-like effects. The
      antidepressant-like effects occurred in the absence of changes in brain
      phospholipid classes. The therapeutic approach of combining omega-3 fatty acids
      with low ineffective doses of antidepressants might represent benefits in the
      treatment of depression, especially in patients with depression resistant to
      conventional treatments and even may contribute to patient compliance by
      decreasing the magnitude of some antidepressant dose-dependent side effects.

PMID- 20826149
TI  - Butein downregulates phorbol 12-myristate 13-acetate-induced COX-2
      transcriptional activity in cancerous and non-cancerous breast cells.
AB  - Butein is a flavonoid isolated from the bark of Rhus verniciflua Stokes and the
      flowers of Butea monosperma, and is known to be a potential therapeutic drug for
      treating inflammation and cancer. Cyclooxygenase (COX) converts arachidonic acid
      to prostanoids, and increased expression of its isoform COX-2 has been observed
      in breast cancer tissues. It has been suggested that COX inhibitors can be used
      as chemopreventive agents against breast carcinogenesis. This study examined the
      potential suppressive effect of the flavonoid on phorbol 12-myristate 13-acetate
      (PMA)-induced COX-2 expression in the non-tumorigenic MCF-10A and cancerous MCF-7
      breast cells. Immunoblot and mRNA analyses revealed that butein at or below 10
      MUM significantly inhibited PMA-induced COX-2 expression in these breast cells.
      The blocking of the PKC signaling pathway appeared to be the underlying
      mechanism. Butein treatment reduced the amount of phospho-mitogen activated
      protein kinase (MAPK) ERK-1/2, and the total activity of PKC. Activated ERKs
      might trigger the transcriptional activation of COX-2. Reporter gene assays as
      well as electrophoretic mobility shift assays (EMSA) illustrated that butein
      inhibited transcription of this gene. This study showed that butein down
      regulated PMA-induced COX-2 expression in both cancerous and non-cancerous breast
      cells, and such findings could provide the basis for pharmaceutical development
      of butein.

PMID- 20826150
TI  - Cellular electrophysiological effects of changrolin in isolated rat cardiac
      myocytes.
AB  - Changrolin (2, 6-bis[pyrrolidin-1-ylmethyl]-4-[quinazolin-4-ylamino] phenol) is
      an anti-arrhythmic drug derived from beta-dichroine, an active component of the
      Chinese medicinal herb, Dichroa febrifuga Lour. To elucidate the mechanism
      underlying the anti-arrhythmic effect of changrolin, we used the whole-cell patch
      clamp technique to characterize the electrophysiological actions of changrolin in
      isolated rat cardiomyocytes. In this study, changrolin inhibited delayed
      rectified K(+) currents (I(K)) in a concentration-dependent manner with
      inhibiting the current by 11.9%+/-4.7%, 27.8%+/-3.4%, 31.5%+/-3.6% and 40.8%+/
      3.7% at 10, 30, 100 and 300 MUM, respectively (n=7-8). Changrolin was less
      effective against transient outward K(+) currents (I(to)), and only showed
      significantly inhibitory effect at the highest concentration (300 MUM).
      Changrolin also induced a concentration-dependent inhibition of sodium currents
      (I(Na)) with an IC(50) of 10.19 MUM (Hill coefficient=-1.727, n=6-7). In
      addition, changrolin exerted a holding potential-dependent block on Na(+)
      channels, produced a hyperpolarizing shift in the steady-state inactivation
      curve, as well as exhibited a marked frequency-dependent component to the
      blockade of Na(+) channels. Finally, calcium currents (I(Ca)) was decreased by
      changrolin in a concentration-dependent manner with an estimated IC(50) of 74.73
      MUM (Hill coefficient=-0.9082, n=6). In conclusion, changrolin blocks Na(+) and
      Ca(2+) channels, and also blocks K(+) channels (I(to) and I(K)) to some extent.
      Notably, changrolin preferentially blocks the inactivated state of Na(+)
      channels. These effects lead to a modification of electromechanical function and
      likely contribute to the termination of arrhythmia.

PMID- 20826151
TI  - Visceral hypersensitivity induced by activation of transient receptor potential
      vanilloid type 1 is mediated through the serotonin pathway in rat colon.
AB  - This study aimed to clarify the relationship between TRPV1 activation-induced
      visceral pain and the serotonin pathway in the colon of rats. The effects of para
      chlorophenylalanine (pCPA) on visceral pain threshold pressure were assessed in
      capsaicin -induced visceral pain of rats. The expression of TRPV1 in the colon
      was examined by immunohistochemistry and Western blot analysis, and TRPV1
      excitability in dorsal root ganglion (DRG) neurons was examined by whole-cell
      patch-clamp recording in pCPA-treated rats. Calcineurin and Ca(2+)-calmodulin
      dependent kinase II (CaMKII), the important proteins in maintaining TRPV1
      function in the colon, were also tested by Western blot analysis and
      immunofluorescence staining. Results showed that pCPA significantly increased the
      capsaicin-induced visceral pain threshold by 2.3-fold, and the enhanced visceral
      pain threshold corresponded with decreased 5-HT content (58% depleted) and
      enterochromaffin cell number (80% reduced). The reduced excitability of TRPV1 in
      DRG neurons, instead of changed TRPV1 expression, is responsible for the enhanced
      visceral pain threshold in 5-HT-depleted rats, and the mechanism may be related
      to the decreased expression of pCaMKII. These results indicate that visceral
      hypersensitivity induced by TRPV1 activation is modulated through 5-HT pathways
      and the attenuated function of TRPV1 and decreased protein expression of pCaMKII
      may play an important role in capsaicin-induced TRPV1 desensitization under 5-HT
      depleted condition. The important role of TRPV1 and 5-HT in generating and
      maintaining visceral hypersensitivity may provide insights for the treatment of
      visceral hypersensitivity.

PMID- 20826152
TI  - TRPV1 receptors are involved in protein nitration and Muller cell reaction in the
      acutely axotomized rat retina.
AB  - We report here the protein expression of TRPV1 receptor in axotomized rat retinas
      and its possible participation in mechanisms involved in retinal ganglion cell
      (RGC) death. Adult rats were subjected to unilateral, intraorbital axotomy of the
      optic nerve, and the retinal tissue was removed for further processing. TRPV1
      total protein expression decreased progressively after optic nerve transection,
      reaching 66.2% of control values 21 days after axotomy. The number of cells
      labeled for TRPV1 in the remnant GCL decreased after 21 days post-lesion (to
      63%). Fluoro-Jade B staining demonstrated that the activation of TRPV1 in acutely
      lesioned eyes elicited more intense neuronal degeneration in the GCL and in the
      inner nuclear layer than in sham-operated retinas. A single intraocular injection
      of capsazepine (100 MUM), a TRPV1 antagonist, 5 days after optic nerve lesion,
      decreased the number of GFAP-expressing Muller cells (72.5% of control values)
      and also decreased protein nitration in the retinal vitreal margin (75.7% of
      control values), but did not affect lipid peroxidation. Furthermore, retinal
      explants were treated with capsaicin (100 MUM), and remarkable protein nitration
      was then present, which was reduced by blockers of the constitutive and inducible
      nitric oxide synthases (7-NI and aminoguanidine, respectively). TRPV1 activation
      also increased GFAP expression, which was reverted by both TRPV1 antagonism with
      capsazepine and by 7-NI and aminoguanidine. Given that Muller cells do not
      express TRPV1, we suppose that the increased GFAP expression in these cells might
      be elicited by TRPV1 activation and by its indirect effect upon nitric oxide
      overproduction and peroxynitrite formation. We incubated Fluorogold pre-labeled
      retinal explants in the presence of capsazepine (1 MUM) during 48 h. The numbers
      of surviving RGCs stained with fluorogold and the numbers of apoptotic cells in
      the GCL detected with TUNEL were similar in lesioned and control retinas. We
      conclude that TRPV1 receptor expression decreased after optic nerve injury due to
      death of TRPV1-containing cells. Furthermore, these data indicate that TRPV1
      might be involved in intrinsic protein nitration and Muller cell reaction
      observed after optic nerve injury.

PMID- 20826153
TI  - Role of TGF-beta in tissue eosinophilia associated with vernal
      keratoconjunctivitis.
AB  - To determine the role of TGF-beta(1) in the tissue eosinophilia associated with
      vernal keratoconjunctivitis (VKC), we investigated the immunohistochemical
      expression of TGF-beta(1) and TGF-beta(1)-related proteins in giant papillae
      obtained from VKC patients. We also investigated the effect of TGF-beta(1) on
      production of eotaxin by cultured conjunctival and corneal fibroblasts using
      ELISA. Finally, the effects of glucocorticoids, cyclosporine, and tacrolimus on
      eotaxin production by corneal fibroblasts were assessed. Our investigations
      revealed that eosinophils expressing TGF-beta(1) and TGF-beta(1)-related proteins
      (such as phosphorylated Smad2, integrin alphavbeta(6), alpha-smooth muscle actin,
      type I procollagen, and tenascin-C) were expressed in the giant papillae. TGF
      beta(1) and IL-4/IL-13 caused a synergistic increase of eotaxin production in
      cultured conjunctival and corneal fibroblasts. This effect of TGF-beta(1) and IL
      4/IL-13 was inhibited by glucocorticoids, but neither by cyclosporine nor by
      tacrolimus. In conclusion, TGF-beta(1) has an important role in the tissue
      eosinophilia associated with VKC.

PMID- 20826154
TI  - Characterization of the intestinal cancer stem cell marker CD166 in the human and
      mouse gastrointestinal tract.
AB  - BACKGROUND & AIMS: CD166 (also called activated leukocyte cell adhesion molecule
      [ALCAM]) is a marker of colorectal cancer (CRC) stem cells; it is expressed by
      aggressive tumors. Although the presence of CD166 at the tumor cell surface has
      been correlated with shortened survival, little is known about its function and
      expression in normal intestinal epithelia. METHODS: We characterized the
      expression pattern of CD166 in normal intestinal tissue samples from humans and
      mice using immunohistochemisty, flow cytometry, and quantitative reverse
      transcriptase polymerase chain reaction. Human and mouse intestinal tumors were
      also analyzed. RESULTS: CD166 was expressed on the surface of epithelial cells
      within the stem cell niche and along the length of the intestine; expression was
      conserved across species. In the small intestine, CD166 was observed on crypt
      based Paneth cells and intervening crypt-based columnar cells (putative stem
      cells). A subset of CD166-positive, crypt-based columnar cells coexpressed the
      stem cell markers Lgr5, Musashi-1, or Dcamkl-1. CD166 was located in the
      cytoplasm and at the surface of cells within human CRC tumors. CD166-positive
      cells were also detected in benign adenomas in mice; rare cells coexpressed CD166
      and CD44 or epithelial-specific antigen. CONCLUSIONS: CD166 is highly expressed
      within the endogenous intestinal stem cell niche. CD166-positive cells appear at
      multiple stages of intestinal carcinoma progression, including benign and
      metastatic tumors. Further studies should investigate the function of CD166 in
      stem cells and the stem cell niche, which might have implications for normal
      intestinal homeostasis. CD166 has potential as a therapeutic target for CRC.

PMID- 20826155
TI  - Bone morphogenetic protein signaling regulates gastric epithelial cell
      development and proliferation in mice.
AB  - BACKGROUND & AIMS: We investigated the role of bone morphogenetic protein (BMP)
      signaling in the regulation of gastric epithelial cell growth and differentiation
      by generating transgenic mice that express the BMP inhibitor noggin in the
      stomach. METHODS: The promoter of the mouse H+/K+-ATPase beta-subunit gene, which
      is specifically expressed in parietal cells, was used to regulate expression of
      noggin in the gastric epithelium of mice. The transgenic mice were analyzed for
      noggin expression, tissue morphology, cellular composition of the gastric mucosa,
      gastric acid content, and plasma levels of gastrin. Tissues were analyzed by
      immunohistochemical, quantitative real-time polymerase chain reaction,
      immunoblot, microtitration, and radioimmunoassay analyses. RESULTS: In the
      stomachs of the transgenic mice, phosphorylation of Smad 1, 5, and 8 decreased,
      indicating inhibition of BMP signaling. Mucosa were of increased height, with
      dilated glands, cystic structures, reduced numbers of parietal cells, and
      increased numbers of cells that coexpressed intrinsic factor, trefoil factor 2,
      and Griffonia (Bandeiraea) simplicifolia lectin II, compared with wild-type mice.
      In the transgenic mice, levels of the H+/K+-ATPase alpha-subunit protein and
      messenger RNA were reduced, whereas those of intrinsic factor increased. The
      transgenic mice were hypochloridric and had an increased number of Ki67- and
      proliferating cell nuclear antigen-positive cells; increased levels of plasma
      gastrin; increased expression of transforming growth factor-alpha, amphiregulin,
      and gastrin; and activation of extracellular signal-regulated kinase 2.
      CONCLUSIONS: Inhibiting BMP signaling in the stomachs of mice by expression of
      noggin causes loss of parietal cells, development of transitional cells that
      express markers of mucus neck and zymogenic lineages, and activation of
      proliferation. BMPs are therefore important regulators of gastric epithelial cell
      homeostasis.

PMID- 20826157
TI  - Underwater survival in the dog tick Dermacentor variabilis (Acari:Ixodidae).
AB  - Ticks are blood-feeding arthropods known for their long survivability off the
      host. Although ticks are terrestrial, they can survive extended periods of time
      submerged underwater. A plastron is an alternative respiration system that can
      absorb oxygen from water via a thin layer of air trapped by hydrophobic hairs or
      other cuticular projections. The complex spiracular plate of ticks has been
      postulated to serve as a plastron but that function has not been verified. This
      study provides evidence of plastron respiration in the American dog tick,
      Dermacentor variabilis, and for the first time confirmed the existence of
      plastron respiration in Ixodidae. Longer survival rates in oxygenated water
      indicate that underwater respiration requires oxygen. Wetting the spiracular
      plate with alcohol debilitates any potential plastron function and lowers the
      survival rate. Survival underwater may also be enhanced by metabolic depression
      and possibly anaerobic respiration. This study describes the first example of
      plastron respiration in the Ixodidae.

PMID- 20826156
TI  - Annexin A2 mediates up-regulation of NF-kappaB, beta-catenin, and stem cell in
      response to progastrin in mice and HEK-293 cells.
AB  - BACKGROUND & AIMS: Prograstrin induces proliferation in colon crypts by
      activating p65nuclear factor-kappaB (NF-kappaB) (p65) and beta-catenin. We
      investigated whether Annexin A2 (AnxA2), a progastrin receptor, activates NF
      kappaB and beta-catenin in vivo. METHODS: ANXA2-null (ANXA2(-/-)) and wild-type
      (ANXA2(+/+)) mice were studied, along with clones of progastrin-responsive HEK
      293 cells that stably expressed full-length progastrin (HEK-mGAS) or an empty
      vector (HEK-C). Small interfering RNA was used to down-regulate AnxA2, p65NF
      kappaB, and beta-catenin in cells. RESULTS: Proliferation and activation of p65
      and beta-catenin increased significantly in HEK-mGAS compared with HEK-C clones.
      HEK-mGAS cells had a 2- to 4-fold increase in relative levels of c-Myc,
      cyclooxygenase (COX)-2, CyclinD1, double cortin CAM kinase-like 1 (DCAMKL+1), and
      CD44, compared with HEK-C clones. Down-regulation of AnxA2 in HEK-mGAS clones
      reduced activation of NF-kappaB and beta-catenin, as well as levels of DCAMKL+1.
      Surprisingly, down-regulation of beta-catenin had no effect on activation of
      p65NF-kappaB, whereas down-regulation of p65 significantly reduced activation of
      beta-catenin in HEK-mGAS clones. Loss of either p65 or beta-catenin significantly
      reduced proliferation of HEK-mGAS clones, indicating that both factors are
      required for the proliferative effects of progastrin. Lengths of colon crypts and
      levels of p65, beta-catenin, DCAMKL+1, and CD44 were significantly higher in
      ANXA2(+/+) mice compared with either ANXA2(-/-) mice given progastrin or
      ANXA2(+/+) and ANXA2(-/-) mice given saline. CONCLUSIONS: AnxA2 expression is
      required for the biologic effects of progastrin in vivo and in vitro and mediates
      the stimulatory effect of progastrin on p65NF-kappa, beta-catenin, and the
      putative stem cell markers DCAMKL+1 and CD44. AnxA2 might therefore mediate the
      hyperproliferative and cocarcinogenic effects of progastrin.

PMID- 20826158
TI  - Effect of light intensity on colour morph formation and performance of the grain
      aphid Sitobion avenae F. (Homoptera: Aphididae).
AB  - The grain aphid Sitobion avenae F., one of the major pest aphids of cereals in
      Central Europe, exhibits colour polymorphism, even within the same clones.
      Although there is evidence that green and brown morphs of S. avenae contain
      different carotenoids, the mechanisms determining the induction of colour morphs
      are unknown. The common understanding is that the formation of colour morphs is
      controlled by light and affected by genetic and environmental factors and by host
      plant species. So far, there is no unequivocal evidence that light intensity,
      photoperiod, or a mixture of several variables are involved in the induction of
      S. avenae colour formation, resulting in the induction of S. avenae colour
      formation and carotenoid synthesis. Here we determined the effect of light
      intensity on the colour formation and performance of ten clones of S. avenae with
      experiments that controlled for the effects of host plant and genetic factors. We
      found that some clones remained green under all test conditions. In other clones,
      colour morph formation was controlled by light. The synthesis of carotenoids
      correlated with changes in colour formation. Host plant did not affect colour
      formation in the ten clones studied. Although colour of the aphid clones did not
      affect their performance, high light intensity increased the fecundity and fresh
      weight of S. avenae clones, while low light intensity stimulated the production
      of alatae.

PMID- 20826159
TI  - Female sex pheromone of a lichen moth Eilema japonica (Arctiidae, Lithosiinae):
      components and control of production.
AB  - Seven candidates for components of the female sex pheromone of Eilema japonica
      (Arctiidae, Lithosiinae) were detected in an extract of pheromone glands with a
      gas chromatograph-electroantennographic detector. The compounds were identified
      as (Z,Z)-6,9-icosadiene (D20), (Z,Z)-6,9-henicosadiene (D21), (Z,Z,Z)-3,6,9
      henicosatriene (T21), (Z,Z)-6,9-docosadiene (D22), (Z,Z,Z)-3,6,9-docosatriene
      (T22), (Z,Z)-6,9-tricosadiene (D23), and (Z,Z,Z)-3,6,9-tricosatriene (T23).
      Assays using synthetic lures in a wind tunnel showed that D21 (proportion, 0.39),
      T21 (0.08), D22 (0.27), and T22 (0.26) are important for evoking full behavioral
      responses from the males. Titers of the pheromone components did not show clear
      temporal fluctuations. Moreover, decapitation of the female moth had no effect on
      the titers of pheromone components in the pheromone gland, suggesting that
      cephalic endocrine factors such as pheromone biosynthesis activating neuropeptide
      (PBAN) are not involved in the control of pheromone biosynthesis in this species.

PMID- 20826160
TI  - Effects of neuropeptide Y on collateral development in a swine model of chronic
      myocardial ischemia.
AB  - We investigated the role of neuropeptide Y (NPY), abundant in the myocardial
      sympathetic nervous system and endothelial cells, in angiogenesis during chronic
      myocardial ischemia. Adult male Yorkshire swine underwent ameroid constrictor
      placement on the proximal left circumflex coronary artery. After 3 weeks, an
      osmotic pump was placed to deliver either placebo (control, n=8) or NPY(3-36)
      (NPY, n=8) to the collateral dependent region. Five weeks after pump placement,
      after cardiac catheterization and hemodynamic assessment, the heart was harvested
      for analysis. NPY treated animals demonstrated increased mean arterial pressures
      and improved left ventricular function (+dP/dt). Cardiac catheterization
      demonstrated a significant increase in the blush score in the NPY group
      (p<0.001). Blood flow to the ischemic myocardium was not different between groups
      at rest or during ventricular pacing. Immunohistochemical double staining for CD
      31 and smooth muscle actin demonstrated an increase in capillary and arteriole
      formation in NPY treated animals (p=0.02 and p<0.001). Immunoblotting showed a
      significant upregulation of DPPIV (p=0.009) and NPY receptors 1 (p=0.008), 2
      (p=0.02) and 5 (p=0.03) in the NPY treated group. Additionally, there was
      significant upregulation of VEGF (p=0.04), eNOS (p=0.014), phospho-eNOS (ser1177)
      (p=0.02), and PDGF (p<0.001) in NPY treated group. The anti-angiogenic factors
      endostatin and angiostatin were significantly decreased in NPY treated animals
      (endostatin, p=0.03; angiostatin, p=0.04). Exogenous NPY(3-36) resulted in
      improved myocardial function and increased angiogenesis and arteriogenesis by
      stimulating growth factor, pro-angiogenic receptor upregulation, and decreasing
      anti-angiogenic expression, but did not increase blood flow to the ischemic
      myocardium. NPY may act as a good adjunct to primary agents of therapeutic
      angiogenesis.

PMID- 20826161
TI  - The solution structure of the C-terminal Ig-like domain of the bacteriophage
      lambda tail tube protein.
AB  - Immunoglobulin (Ig)-like domains are found frequently on the surface of tailed
      double-stranded DNA bacteriophages, yet their functional role remains obscure.
      Here, we have investigated the structure and function of the C-terminal Ig-like
      domain of gpV (gpV(C)), the tail tube protein of phage lambda. This domain has
      been predicted through sequence similarity to be a member of the bacterial Ig
      like domain 2 (Big_2) family, which is composed of more than 1300 phage and
      bacterial sequences. Using trypsin proteolysis, we have delineated the boundaries
      of gpV(C) and have shown that its removal reduces the biological activity of gpV
      by 100-fold; thus providing a definitive demonstration of a functional role for
      this domain. Determination of the solution structure of gpV(C) by NMR
      spectroscopy showed that it adopts a canonical Ig-like fold of the I-set class.
      This represents the first structure of a phage-encoded Ig-like domain and only
      the second structure of a Big_2 domain. Structural and sequence comparisons
      indicate that the gpV(C) structure is more representative of both the phage
      encoded Big_2 domains and Big_2 domains in general than the other available Big_2
      structure. Bioinformatics analyses have identified two conserved clusters of
      residues on the surface of gpV(C) that may be important in mediating the function
      of this domain.

PMID- 20826162
TI  - Structural insights into substrate specificity in variants of N-acetylneuraminic
      Acid lyase produced by directed evolution.
AB  - The substrate specificity of Escherichia coli N-acetylneuraminic acid lyase was
      previously switched from the natural condensation of pyruvate with N
      acetylmannosamine, yielding N-acetylneuraminic acid, to the aldol condensation
      generating N-alkylcarboxamide analogues of N-acetylneuraminic acid. This was
      achieved by a single mutation of Glu192 to Asn. In order to analyze the
      structural changes involved and to more fully understand the basis of this switch
      in specificity, we have isolated all 20 variants of the enzyme at position 192
      and determined the activities with a range of substrates. We have also determined
      five high-resolution crystal structures: the structures of wild-type E. coli N
      acetylneuraminic acid lyase in the presence and in the absence of pyruvate, the
      structures of the E192N variant in the presence and in the absence of pyruvate,
      and the structure of the E192N variant in the presence of pyruvate and a
      competitive inhibitor (2R,3R)-2,3,4-trihydroxy-N,N-dipropylbutanamide. All
      structures were solved in space group P2(1) at resolutions ranging from 1.65 A to
      2.2 A. A comparison of these structures, in combination with the specificity
      profiles of the variants, reveals subtle differences that explain the details of
      the specificity changes. This work demonstrates the subtleties of enzyme
      substrate interactions and the importance of determining the structures of
      enzymes produced by directed evolution, where the specificity determinants may
      change from one substrate to another.

PMID- 20826163
TI  - The 2.2-A structure of the HP0958 protein from Helicobacter pylori reveals a
      kinked anti-parallel coiled-coil hairpin domain and a highly conserved ZN-ribbon
      domain.
AB  - We have determined the 2.2-A structure of the HP0958 protein from the human
      gastric pathogen Helicobacter pylori. HP0958 is essential for flagellum formation
      and motility. It functions as a chaperone for RpoN (sigma(54)) and also controls
      the stability and translation of mRNA for the major flagellin subunit FlaA. The
      protein is composed of a highly elongated and kinked coiled-coil hairpin domain
      (residues 1-170), followed by a C(4) Zn-ribbon domain (residues 174-238). The Zn
      ribbon domain is rich in aromatic and positively charged amino acid residues.
      Electrophoretic mobility shift assays identified residues in a positively charged
      region of the Zn-ribbon domain of HP0958 whose mutation alters the mobility of an
      HP0958-flaA mRNA complex. Mutation of surface residues in the coiled-coil domain
      did not result in an observable change in the mobility of the HP0958-flaA
      transcript complex. The data thus suggest the arrangement of HP0958 into distinct
      structural and functional domains.

PMID- 20826164
TI  - Determinants of substrate binding and protonation in the flavoenzyme xenobiotic
      reductase A.
AB  - Xenobiotic reductase A (XenA) from Pseudomonas putida 86 catalyzes the NAD(P)H
      dependent reduction of various alpha,beta-unsaturated carbonyl compounds and is a
      member of the old yellow enzyme family. The reaction of XenA follows a ping-pong
      mechanism, implying that its active site has to accommodate and correctly
      position the various substrates to be oxidized (NADH/NADPH) and to be reduced
      (different alpha,beta-unsaturated carbonyl compounds) to enable formal hydride
      transfers between the substrate and the isoalloxazine ring. The active site of
      XenA is lined by two tyrosine (Tyr27, Tyr183) and two tryptophan (Trp302, Trp358)
      residues, which were proposed to contribute to substrate binding. We analyzed the
      individual contributions of the four residues, using site-directed mutagenesis,
      steady-state and transient kinetics, redox potentiometry and crystal structure
      analysis. The Y183F substitution decreases the affinity of XenA for NADPH and
      reduces the rate of the oxidative half-reaction by two to three orders of
      magnitude, the latter being in agreement with its function as a proton donor in
      the oxidative half-reaction. Upon reduction of the flavin, Trp302 swings into the
      active site of XenA (in-conformation) and decreases the extent of the substrate
      binding pocket. Its exchange against alanine induces substrate inhibition at
      elevated NADPH concentrations, indicating that the in-conformation of Trp302
      helps to disfavor the nonproductive NADPH binding in the reduced state of XenA.
      Our analysis shows that while the principal catalytic mechanism of XenA, for
      example, type of proton donor, is analogous to that of other members of the old
      yellow enzyme family, its strategy to correctly position and accommodate
      different substrates is unprecedented.

PMID- 20826165
TI  - Identification of an allosteric signaling network within Tec family kinases.
AB  - The Tec family kinases are tyrosine kinases that function primarily in
      hematopoietic cells. The catalytic activity of the Tec kinases is positively
      influenced by the regulatory domains outside of the kinase domain. The current
      lack of a full-length Tec kinase structure leaves a void in our understanding of
      how these positive regulatory signals are transmitted to the kinase domain.
      Recently, a conserved structure within kinases, the 'regulatory spine', which
      assembles and disassembles as a kinase switches between its active and inactive
      states, has been identified. Here, we define the residues that comprise the
      regulatory spine within Tec kinases. Compared to previously characterized
      systems, the Tec kinases contain an extended regulatory spine that includes a
      conserved methionine within the C-helix and a conserved tryptophan within the Src
      homology 2-kinase linker of Tec kinases. This extended regulatory spine forms a
      conduit for transmitting the presence of the regulatory domains of Tec kinases to
      the catalytic domain. We further show that mutation of the gatekeeper residue at
      the edge of the regulatory spine stabilizes the regulatory spine, resulting in a
      constitutively active kinase domain. Importantly, the regulatory spine is
      preassembled in this gatekeeper mutant, rendering phosphorylation on the
      activation loop unnecessary for its activity. Moreover, we show that the
      disruption of the conserved electrostatic interaction between Bruton's tyrosine
      kinase R544 on the activation loop and Bruton's tyrosine kinase E445 on the C
      helix also aids in the assembly of the regulatory spine. Thus, the extended
      regulatory spine is a key structure that is critical for maintaining the activity
      of Tec kinases.

PMID- 20826167
TI  - Fifty years of JTB: past, present and future: a letter from the Editors-in-Chief.

PMID- 20826166
TI  - Mechanism of dephosphorylation of the SR protein ASF/SF2 by protein phosphatase
      1.
AB  - SR proteins are essential splicing factors whose function is controlled by multi
      site phosphorylation of a C-terminal domain rich in arginine-serine repeats (RS
      domain). The protein kinase SRPK1 has been shown to polyphosphorylate the N
      terminal portion of the RS domain (RS1) of the SR protein ASF/SF2, a modification
      that promotes nuclear entry of this splicing factor and engagement in splicing
      function. Later, dephosphorylation is required for maturation of the spliceosome
      and other RNA processing steps. While phosphates are attached to RS1 in a
      sequential manner by SRPK1, little is known about how they are removed. To
      investigate factors that control dephosphorylation, we monitored region-specific
      mapping of phosphorylation sites in ASF/SF2 as a function of the protein
      phosphatase PP1. We showed that 10 phosphates added to the RS1 segment by SRPK1
      are removed in a preferred N-to-C manner, directly opposing the C-to-N
      phosphorylation by SRPK1. Two N-terminal RNA recognition motifs in ASF/SF2
      control access to the RS domain and guide the directional mechanism. Binding of
      RNA to the RNA recognition motifs protects against dephosphorylation, suggesting
      that engagement of the SR protein with exonic splicing enhancers can regulate
      phosphoryl content in the RS domain. In addition to regulation by N-terminal
      domains, phosphorylation of the C-terminal portion of the RS domain (RS2) by the
      nuclear protein kinase Clk/Sty inhibits RS1 dephosphorylation and disrupts the
      directional mechanism. The data indicate that both RNA-protein interactions and
      phosphorylation in flanking sequences induce conformations of ASF/SF2 that
      increase the lifetime of phosphates in the RS domain.

PMID- 20826168
TI  - Predicting the state of cysteines based on sequence information.
AB  - A three-stage support vector machine (SVM) was constructed to predict the state
      of cysteines by fusing sequence information, evolution information and annotation
      information of protein sequences. The first and second stages were for predicting
      whether the protein sequences contain disulfide bonds and whether all of the
      cysteines are involved in disulfide bonds. In the last stage, one SVM was
      constructed for predicting which cysteines are involved in disulfide bonds, among
      all these cysteines in proteins. The three SVMs give a good performance and the
      overall prediction accuracy are 90.05%, 96.36% and 80.00%, respectively, which
      indicates that the features selected in this work are effective for predicting
      the state of cysteines. In addition, current methods only paid too much attention
      to the prediction performance and never showed us how much important the roles of
      these features played in the prediction. As a result a feature importance
      measurement designated as F-score function was used to evaluate these features.
      The result shows that among these protein descriptors; evolution information is
      the most important feature for representing the disulfide-containing proteins.
      The prediction software and data sets used in this article are freely available
      at http://cic.scu.edu.cn/bioinformatics/Predict_Cys.zip.

PMID- 20826169
TI  - Protein intake induced an increase in exercise stimulated fat oxidation during
      stable body weight.
AB  - BACKGROUND: Protein-rich weight-loss diets spare fat-free mass at the cost of fat
      mass. The objective was to examine if there is a change in stimulated fat
      oxidation related to protein intake during stable body weight. METHODS: Subjects'
      (BMI 22+/-2kg/m(2), age 25+/-8 years) maximal fat oxidation (Fat(max)) was
      assessed during a graded bicycle test, before and after a 3-month dietary
      intervention of 2MJ/day supplements exchanged with 2MJ/d of habitual energy
      intake. The parallel design consisted of protein-rich supplements in the protein
      group and an isocaloric combination of carbohydrate and fat supplements in the
      control group. Daily protein intake was determined according to 24-h urine
      nitrogen. Body composition was measured according to a 4-compartment model by a
      combination of underwater-weighing technique, deuterium-dilution technique and
      whole-body dual-energy X-ray absorptiometry (DXA). RESULTS: Subjects were weight
      stable and did not change their physical activity. The protein group (n=12)
      increased protein intake (11+/-14g, P<0.05) and had significantly higher daily
      protein intake vs. control (n=4) (80+/-21 vs.59+/-11g, P<0.05). Fat(max)
      increased significantly in the protein group (0.08+/-0.08g/min, P<0.01). Fat-free
      mass increased independent of change in body weight (P<0.01), and fat mass and
      fat percentage decreased (P<0.05). Change in Fat(max) was a function of change in
      protein intake (r=0.623, P<0.05), and not of changes in body composition or
      VO(2)max. CONCLUSION: Increased stimulated fat oxidation was related to increased
      protein intake.

PMID- 20826170
TI  - Oral nicotine consumption does not affect maternal care or early development in
      mice but results in modest hyperactivity in adolescence.
AB  - Nicotine exposure during development can alter behavior in adulthood in mice. One
      route of nicotine administration that can mimic some of the dynamics of human
      smoking is administration of the drug to pregnant and nursing mice through the
      drinking water. It is critical to determine if nicotine administration has an
      impact on maternal behavior as such changes could lead to persistent behavioral
      alterations in the offspring, independent of the neuropharmacological effects of
      the drug. While a number of studies have detected nicotine exposure-induced
      changes, the effects of nicotine administration through the drinking water on
      maternal behavior in mice have not been examined comprehensively. In the current
      study we have compared maternal behaviors of C57BL/6J mice exposed to nicotine in
      the drinking water to behaviors of animals exposed to saccharin (vehicle) in the
      drinking water for the first 7days after birth of their litters and find no
      significant between-group differences in any behaviors measured except passive
      nursing. We have also assessed the effects of nicotine administration through the
      drinking water on postnatal weight gain of the pups and find no significant
      differences between groups. Open-field locomotor activity differences between
      exposed and unexposed offspring in adolescence were also assessed, with transient
      hyperactivity detected in nicotine-exposed mice. These data suggest that
      behavioral differences identified between animals exposed to nicotine through
      maternal drinking water administration are primarily due to the
      neuropharmacological effects of the drug and not due to effects of exposure on
      maternal behavior.

PMID- 20826171
TI  - Effects of sex, litter size and periconceptional ewe nutrition on offspring
      behavioural and physiological response to isolation.
AB  - Maternal periconceptional undernutrition alters fetal hypothalamic-pituitary
      adrenal (HPA) axis development. However, the effects of this early nutritional
      insult on postnatal HPA axis function and stress-related behaviours are unknown.
      We investigated in sheep the effects of different periods of undernutrition, and
      of sex and litter size, on offspring behavioural and cortisol responses to
      isolation stress. We studied four nutritional groups: controls well nourished
      throughout pregnancy (n=39), or ewes undernourished (UN, 10-15% body weight
      reduction) before mating (-60 to 0d, n=26), after mating (-2 to +30d, n=20) or
      both (-60 to +30d, n=36). At 4 and 18months of age, offspring were isolated for
      5min, their behaviour video recorded, and plasma cortisol concentrations
      measured. Offspring of all undernourished groups demonstrated 50% fewer escape
      attempts than controls at 4 months of age, and offspring of UN-60+30 ewes had 20%
      lower plasma cortisol area under the curve in response to isolation at 18months.
      Females had higher cortisol concentrations and vocalised more than males at 4 and
      18months, and were more active at 18months. After isolation, UN-2+30 males had
      higher cortisol concentrations than UN-2+30 females whereas in all other groups
      males had lower concentrations than females. Singleton males made more escape
      attempts than females, whereas in twins females made more escape attempts than
      males. These findings suggest that maternal periconceptional undernutrition in
      sheep can suppress behavioural reactions and cortisol secretion in response to
      isolation stress in the offspring into adulthood, and that these effects differ
      between males and females.

PMID- 20826172
TI  - Stereoselective construction of a steroid 5alpha,7alpha-oxymethylene derivative
      and its use in the synthesis of eplerenone.
AB  - A new and practical method for a stereoselective construction of a steroid
      5alpha,7alpha-oxymethylene derivative has been developed and successfully applied
      to the stereoselective synthesis of eplerenone (8). Starting with available
      11alpha-hydroxyl canrenone (1), eplerenone (8) was synthesised in seven steps
      with a 48% overall yield.

PMID- 20826173
TI  - Evolution in heterogeneous populations: from migration models to fixation
      probabilities.
AB  - Although dispersal is recognized as a key issue in several fields of population
      biology (such as behavioral ecology, population genetics, metapopulation dynamics
      or evolutionary modeling), these disciplines focus on different aspects of the
      concept and often make different implicit assumptions regarding migration models.
      Using simulations, we investigate how such assumptions translate into effective
      gene flow and fixation probability of selected alleles. Assumptions regarding
      migration type (e.g. source-sink, resident pre-emption, or balanced dispersal)
      and patterns (e.g. stepping-stone versus island dispersal) have large impacts
      when demes differ in sizes or selective pressures. The effects of fragmentation,
      as well as the spatial localization of newly arising mutations, also strongly
      depend on migration type and patterns. Migration rate also matters: depending on
      the migration type, fixation probabilities at an intermediate migration rate may
      lie outside the range defined by the low- and high-migration limits when demes
      differ in sizes. Given the extreme sensitivity of fixation probability to
      characteristics of dispersal, we underline the importance of making explicit (and
      documenting empirically) the crucial ecological/ behavioral assumptions
      underlying migration models.

PMID- 20826174
TI  - Envenoming following bites by the Balkan adder Vipera berus bosniensis - first
      documented case series from Bulgaria.
AB  - We report the first detailed accounts of bites by the Balkan adder, Vipera berus
      bosniensis from Bulgaria. Documentation of bites by this subspecies is very rare
      in the literature and most available accounts are from the northern limit of its
      distribution. V. berus bosniensis is considered to possess neurotoxic venom but
      little evidence has hitherto been available to support this supposition. In this
      case series symptoms typical of adder bites developed including oedema, nausea,
      dizziness, lymphangitis, vomiting, and diarrhoea together with aberrant symptoms
      such as diplopia and ptosis that confirm the presence of neurotoxic venom in
      Balkan adders. In addition, unusual and atypical symptoms of adder bites such as
      painless bites and muscle cramps appeared. The inadequate treatment in hospital
      and the remote habitats in which this species is encountered are potential
      sources of complication.

PMID- 20826175
TI  - Cardiotoxic effects of Loxosceles intermedia spider venom and the recombinant
      venom toxin rLiD1.
AB  - Loxosceles spider bites cause many human injuries worldwide. Injections in mice
      of whole Loxosceles (L.) intermedia venom or a recombinant toxin (rLiD1) produce
      systemic symptoms similar to those detected in envenomed humans. This animal
      model was used to characterize the effects of Loxosceles intermedia venom in
      cardiac tissues. L. intermedia antigens were detected by ELISA in kidney, heart,
      lung and liver of experimentally envenomed mice. In addition, rLiD1 binding to
      cardiomyocytes was demonstrated by immunofluorescence and confocal microscopy.
      Furthermore, isolated perfused heart preparations and ventricular cardiomyocytes
      from envenomed mice showed heart function impairment, and a significant increase
      of I(Ca,L) density and intracellular Ca(2+) transients, respectively. Thus, L.
      intermedia spider venom, as shown through the use of the recombinant toxin rLiD1,
      causes cardiotoxic effects and a protein from the sphingomyelinase D family plays
      a key role in heart dysfunction. Thus, L. intermedia spider venom and the Loxtox
      rLiD1 play a key role in heart dysfunction.

PMID- 20826176
TI  - Morphologies of mouse retinal ganglion cells expressing transcription factors
      Brn3a, Brn3b, and Brn3c: analysis of wild type and mutant cells using genetically
      directed sparse labeling.
AB  - The mammalian retina contains more than 50 distinct neuronal types, which are
      broadly classified into several major classes: photoreceptor, bipolar,
      horizontal, amacrine, and ganglion cells. Although some of the developmental
      mechanisms involved in the differentiation of retinal ganglion cells (RGCs) are
      beginning to be understood, there is little information regarding the genetic and
      molecular determinants of the distinct morphologies of the 15-20 mammalian RGC
      cell types. Previous work has shown that the transcription factor Brn3b/Pou4f2
      plays a major role in the development and survival of many RGCs. The roles of the
      closely related family members, Brn3a/Pou4f1 and Brn3c/Pou4f3 in RGC development
      are less clear. Using a genetically-directed method for sparse cell labeling and
      sparse conditional gene ablation in mice, we describe here the sets of RGC types
      in which each of the three Brn3/Pou4f transcription factors are expressed and the
      consequences of ablating these factors on the development of RGC morphologies.

PMID- 20826177
TI  - Spatial perception during pursuit initiation.
AB  - Spatial perception is modulated by eye movements. During smooth pursuit,
      perceived locations are shifted in the direction of the eye movement. During
      active fixation, visual space is perceptually compressed towards the fovea. In
      our present study, we were interested to determine the time course of spatial
      localization during pursuit initiation, i.e. the transition period from fixation
      to steady-state pursuit. Human observers had to localize briefly flashed targets
      around the time of pursuit initiation. Our data clearly show that pursuit-like
      mislocalization starts well before the onset of the eye movement. Our results
      point towards corollary-discharge as neural source for the observed perceptual
      effect.

PMID- 20826178
TI  - Microinjection of histamine into the dentate gyrus produces antinociception in
      the formalin test in rats.
AB  - The present study was aimed to investigate the effects of microinjection of
      histamine, chlorpheniramine (a histamine H(1) receptor antagonist), ranitidine (a
      histamine H(2) receptor antagonist) and thioperamide (a histamine H(3) receptor
      antagonist) into the dentate gyrus on the formalin-induced pain. A biphasic
      pattern (first phase: 0-5min and second phase: 15-60min) in nociceptive responses
      was induced after subcutaneous injection of formalin (50MUl, 2.5%) into the
      ventral surface of the right hind paw. Microinjection of histamine (1 and 2MUg)
      into the dentate gyrus decreased the intensity of nociceptive responses. Intra
      dentate gyrus microinjection of chlorpheniramine and ranitidine at the same doses
      of 1 and 4MUg had no effects, whereas thioperamide at a dose of 4MUg suppressed
      both phases of formalin-induced pain. Pretreatments with chlorpheniramine and
      ranitidine at the same dose of 4MUg prevented histamine (2MUg)-induced
      antinociception, while thioperamide (4MUg) increased histamine (2MUg)-induced
      antinociception. These results indicated that activation of brain neuronal
      histamine at the levels of dentate gyrus produced antinociception. The post
      synaptic H(1), H(2) receptors and pre-synaptic H(3) receptors of histamine may be
      involved in the histamine-induced antinociception at the level of the dentate
      gyrus.

PMID- 20826179
TI  - Suicidal brains: a review of functional and structural brain studies in
      association with suicidal behaviour.
AB  - Evidence of an association between a vulnerability to suicidal behaviour and
      neurobiological abnormalities is accumulating. Post-mortem studies have
      demonstrated structural and biochemical changes in the brains of suicide victims.
      More recently, imaging techniques have become available to study changes in the
      brain in vivo. This systematic review of comparative imaging studies of suicidal
      brains shows that changes in the structure and functions of the brain in
      association with suicidal behaviour are mainly found in the orbitofrontal and
      dorsolateral parts of the prefrontal cortex. Correlational studies suggest that
      these changes relate to neuropsychological disturbances in decision-making,
      problem solving and fluency, respectively. As a consequence, the findings from
      these studies suggest that suicidal behaviour is associated with (1) a particular
      sensitivity to social disapproval (2) choosing options with high immediate reward
      and (3) a reduced ability to generate positive future events. Further study is
      needed to elaborate these findings and to investigate to what extent changes in
      the structure and function of suicidal brains are amenable to psychological
      and/or biological interventions.

PMID- 20826180
TI  - Pathophysiological relevance of NO signaling in the cardiovascular system: novel
      insight from mice lacking all NO synthases.
AB  - Nitric oxide (NO) exerts a variety of biological actions under both physiological
      and pathological conditions. NO is synthesized by three distinct NO synthase
      (NOS) isoforms, including neuronal (nNOS), inducible (iNOS), and endothelial NOS
      (eNOS), all of which are expressed in the human cardiovascular system. The roles
      of endogenous NO in the cardiovascular system have been investigated in
      pharmacological studies with NOS inhibitors and in studies with mice that lack
      each NOS isoform. However, in the pharmacological studies, the specificity of the
      NOS inhibitors continues to be an issue of debate, while in each of the NOS
      isoform-deficient mice, a compensatory mechanism by other NOSs that are not
      genetically deleted is apparently involved. Thus, the authentic roles of
      endogenous NO are still poorly understood. To address this issue, genetically
      engineered mice in which all three NOS genes are completely disrupted have been
      developed. In the triply n/i/eNOS(-/-) mice, but not in singly eNOS(-/-) mice,
      several cardiovascular phenotypes, including arteriosclerosis/atherosclerosis,
      myocardial infarction, and dyslipidemia, have been described. Furthermore, by
      using the triply NOS(-/-) mice, the roles of the NOS system in endothelium
      dependent hyperpolarization and stain-induced NO production have been elucidated.
      These results provide novel insight into the cardiovascular role of the
      endogenous NO/NOS system at the molecular level. This review, based on the
      research outcomes obtained from the triply NOS(-/-) genetic model, summarizes the
      latest knowledge of the pathophysiological relevance of NO signaling in the
      cardiovascular system.

PMID- 20826182
TI  - Recent advances on the use of the CXCR4 antagonist plerixafor (AMD3100,
      MozobilTM) and potential of other CXCR4 antagonists as stem cell mobilizers.
AB  - AMD3100 was originally discovered as an anti-HIV agent effective in inhibiting
      the replication of HIV in vitro at nanomolar concentrations. We found it to be a
      potent and selective antagonist of CXCR4, the receptor for the chemokine SDF-1
      (now called CXCL12). AMD3100 was then developed, and marketed, as a stem cell
      mobilizer, and renamed plerixafor (MozobilTM). The path to the discovery of
      MozobilTM as a stem cell mobilizer was described in Biochem. Pharmacol. 77: 1655
      1664 (2009). Here I review the recent advances that have consolidated the role of
      plerixafor in mobilizing hematopoietic stem cells (HSCs) and hematopoietic
      progenitor cells (HPCs) from the bone marrow into the blood circulation.
      Plerixafor acts synergistically with granulocyte colony-stimulating factor (G
      CSF), and its usefulness has been proven particularly for the mobilization of
      HSCs and HPCs for autologous stem cell transplantation in patients with non
      Hodgkin's lymphoma (NHL) or multiple myeloma (MM). Plerixafor also has great
      potential for the treatment of hematological malignancies other than NHL and MM,
      and non-hematological malignancies, and, eventually, several other diseases
      depending on the CXCL12-CXCR4 interaction. Various AMD3100 analogs have been
      described (i.e. AMD11070, AMD3465, KRH-3955, T-140, and 4F-benzoyl-TN14003),
      primarily as potential anti-HIV agents. They are all strong CXCR4 antagonists.
      Their role in stem cell mobilization remains to be assessed.

PMID- 20826183
TI  - Blink detection robust to various facial poses.
AB  - Applications based on eye-blink detection have increased, as a result of which it
      is essential for eye-blink detection to be robust and non-intrusive irrespective
      of the changes in the user's facial pose. However, most previous studies on
      camera-based blink detection have the disadvantage that their performances were
      affected by the facial pose. They also focused on blink detection using only
      frontal facial images. To overcome these disadvantages, we developed a new method
      for blink detection, which maintains its accuracy despite changes in the facial
      pose of the subject. This research is novel in the following four ways. First,
      the face and eye regions are detected by using both the AdaBoost face detector
      and a Lucas-Kanade-Tomasi (LKT)-based method, in order to achieve robustness to
      facial pose. Secondly, the determination of the state of the eye (being open or
      closed), needed for blink detection, is based on two features: the ratio of
      height to width of the eye region in a still image, and the cumulative difference
      of the number of black pixels of the eye region using an adaptive threshold in
      successive images. These two features are robustly extracted irrespective of the
      lighting variations by using illumination normalization. Thirdly, the accuracy of
      determining the eye state - open or closed - is increased by combining the above
      two features on the basis of the support vector machine (SVM). Finally, the SVM
      classifier for determining the eye state is adaptively selected according to the
      facial rotation. Experimental results using various databases showed that the
      blink detection by the proposed method is robust to various facial poses.

PMID- 20826184
TI  - Inhibition of influenza virus replication by plant-derived isoquercetin.
AB  - Influenza virus infects the respiratory system of human and animals causing mild
      to severe illness which could lead to death. Although vaccines are available,
      there is still a great need for influenza antiviral drugs to reduce disease
      progression and virus transmission. Currently two classes (M2 channel blockers
      and neuraminidase inhibitors) of FDA-approved influenza antiviral drugs are
      available, but there are great concerns of emergence of viral resistance.
      Therefore, timely development of new antiviral drugs against influenza viruses is
      crucial. Plant-derived polyphenols have been studied for antioxidant activity,
      anti-carcinogenic, and cardio- and neuroprotective actions. Recently, some
      polyphenols, such as resveratrol and epigallocatechin gallate, showed significant
      anti-influenza activity in vitro and/or in vivo. Therefore we investigated
      selected polyphenols for their antiviral activity against influenza A and B
      viruses. Among the polyphenols we tested, isoquercetin inhibited the replication
      of both influenza A and B viruses at the lowest effective concentration. In a
      double treatment of isoquercetin and amantadine, synergistic effects were
      observed on the reduction of viral replication in vitro. The serial passages of
      virus in the presence of isoquercetin did not lead to the emergence of resistant
      virus, and the addition of isoquercetin to amantadine or oseltamivir treatment
      suppressed the emergence of amantadine- or oseltamivir-resistant virus. In a
      mouse model of influenza virus infection, isoquercetin administered
      intraperitoneally to mice inoculated with human influenza A virus significantly
      decreased the virus titers and pathological changes in the lung. Our results
      suggest that isoquercetin may have the potential to be developed as a therapeutic
      agent for the treatment of influenza virus infection and for the suppression of
      resistance in combination therapy with existing drugs.

PMID- 20826185
TI  - Involvement of WSSV-shrimp homologs in WSSV infectivity in kuruma shrimp:
      Marsupenaeus japonicus.
AB  - White spot syndrome virus (WSSV) is pathogenic and specific to shrimp, and is
      capable of producing a persistent infection in the host. Moreover, shrimp are
      capable of persistently carrying a single or multiple viruses, allowing them to
      survive for long periods with latent infections. In order to identify genes that
      are specially involved in the intricate WSSV-shrimp association, we focused on
      homologs between the WSSV and shrimp genomes. We here investigated whether
      homologous WssvORFs (WssvORF285, WssvORF332) and their homologs in the kuruma
      shrimp genome (MjORF16, MjORF18) are important for WSSV infectivity by utilizing
      dsRNA-mediated RNA interference, and further proposed potential roles of
      homologous WssvORFs associated with the persistent viral infection stage.
      Homologous MjORFs were found to be highly up-regulated in several tested tissues
      upon WSSV infection. Injection of dsRNAs specific to homologous MjORFs, followed
      by WSSV challenge, led to reduced and delayed shrimp mortality when compared to
      that of shrimp without dsRNA injection. Silencing of homologous WssvORFs by
      specific dsRNAs sharply increased shrimp survival. WssvORF332 may function as a
      latency gene especially associated with the persistent WSSV infection stage while
      WssvORF285 may be classified into the same group as WssvVP28 and may play a role
      in virus penetration during the infection. Our results suggest that WSSV-shrimp
      homologs are involved in WSSV infectivity and support the hypothesis that
      homologous WssvORFs are related to WSSV latency and pathogenesis.

PMID- 20826181
TI  - Therapeutic utility of non-peptidic CRF1 receptor antagonists in anxiety,
      depression, and stress-related disorders: evidence from animal models.
AB  - Adaptive responding to threatening stressors is of fundamental importance for
      survival. Dysfunctional hyperactivation of corticotropin releasing factor type-1
      (CRF(1)) receptors in stress response system pathways is linked to stress-related
      psychopathology and CRF(1) receptor antagonists (CRAs) have been proposed as
      novel therapeutic agents. CRA effects in diverse animal models of stress that
      detect anxiolytics and/or antidepressants are reviewed, with the goal of
      evaluating their potential therapeutic utility in depression, anxiety, and other
      stress-related disorders. CRAs have a distinct phenotype in animals that has
      similarities to, and differences from, those of classic antidepressants and
      anxiolytics. CRAs are generally behaviorally silent, indicating that CRF(1)
      receptors are normally in a state of low basal activation. CRAs reduce stressor
      induced HPA axis activation by blocking pituitary and possibly brain CRF(1)
      receptors which may ameliorate chronic stress-induced pathology. In animal models
      sensitive to anxiolytics and/or antidepressants, CRAs are generally more active
      in those with high stress levels, conditions which may maximize CRF(1) receptor
      hyperactivation. Clinically, CRAs have demonstrated good tolerability and safety,
      but have thus far lacked compelling efficacy in major depressive disorder,
      generalized anxiety disorder, or irritable bowel syndrome. CRAs may be best
      suited for disorders in which stressors clearly contribute to the underlying
      pathology (e.g. posttraumatic stress disorder, early life trauma,
      withdrawal/abstinence from addictive substances), though much work is needed to
      explore these possibilities. An evolving literature exploring the genetic,
      developmental and environmental factors linking CRF(1) receptor dysfunction to
      stress-related psychopathology is discussed in the context of improving the
      translational value of current animal models.

PMID- 20826186
TI  - Transcranial direct current stimulation decreases convulsions and spatial memory
      deficits following pilocarpine-induced status epilepticus in immature rats.
AB  - PURPOSE: Transcranial direct current stimulation (tDCS) is a recently available,
      noninvasive brain stimulation technique. The effects of cathodal tDCS on
      convulsions and spatial memory after status epilepticus (SE) in immature animals
      were investigated. METHODS: Rats underwent lithium-pilocarpine-induced SE at
      postnatal day (P) 20-21 and received daily 30-min cathodal tDCS for 2 weeks at
      P23-36 through a unilateral epicranial electrode at 200MUA. After tDCS,
      convulsions over 2 weeks were estimated by 20-h/day video monitoring. The rats
      were tested in a water maze for spatial learning at P50-53 and the brains were
      examined for cell loss and mossy fiber sprouting. RESULTS: Long-term treatment
      with weak cathodal tDCS reduced SE-induced hippocampal cell loss, supragranular
      and CA3 mossy fiber sprouting, and convulsions (reduction of 21%) in immature
      rats. The tDCS treatment also rescued cognitive impairment following SE.
      CONCLUSIONS: These findings suggested that cathodal tDCS has neuroprotective
      effects on the immature rat hippocampus after pilocarpine-induced SE, including
      reduced sprouting and subsequent improvements in cognitive performance. Such
      treatment might also have an antiepileptic effect.

PMID- 20826187
TI  - Auditory brainstem measures predict reading and speech-in-noise perception in
      school-aged children.
AB  - Reading and speech-in-noise perception, fundamental aspects of human
      communication, have been linked to neural indices of auditory brainstem function.
      However, how these factors interact is currently unclear. Multivariate analysis
      methods (structural equation modeling) were employed to delineate and quantify
      the relationships among factors that relate to successful reading and speech in
      noise perception in children. Neural measures of subcortical speech encoding that
      reflect the utilization of stimulus regularities, differentiation of stop
      consonants, and robustness of neural synchrony predicted 73% of the variance in
      reading scores. A different combination of neural measures, specifically,
      utilization of stimulus regularities, strength of encoding of lower harmonics,
      and the extent of noise-induced timing delays uniquely predicted 56% of the
      variance in speech-in-noise perception measures. The neural measures relating to
      reading and speech-in-noise perception were substantially non-overlapping and
      resulted in poor fitting models when substituted for each other, thereby
      suggesting distinct neural signatures for the two skills. When phonological
      processing and working memory measures were added to the models, brainstem
      measures still uniquely predicted variance in reading ability and speech-in-noise
      perception, highlighting the robustness of the relationship between subcortical
      auditory function and these skills. The current study suggests that objective
      neural markers may prove valuable in the assessment of reading or speech-in-noise
      abilities in children.

PMID- 20826188
TI  - The effects of repeated social interaction stress on behavioural and
      physiological parameters in a stress-sensitive mouse strain.
AB  - Stress can impair the immune, endocrine and nervous systems. Such perturbations
      can also affect brain-gut axis communication and lead to functional
      gastrointestinal disorders such as irritable bowel syndrome (IBS). IBS is a
      common yet poorly understood disorder which is often co-morbid with anxiety and
      depression. As there are few mouse models of IBS, this study aimed to investigate
      if a short and intense social stress which involved bouts of physical interaction
      could induce behavioural and physiological changes similar to those observed in
      IBS patients in the innately anxious BALB/c mice. Male BALB/c mice were exposed
      for 2h to an aggressive male intruder for acute (one-day) or chronic (six-day)
      stress. Behaviour was analyzed and weight monitored. Two hours post stress, trunk
      blood and tissues were collected. Plasma was analyzed for inflammatory cytokines
      and corticosterone and morphological damage to the colon was also assessed. Mice
      displayed either dominant or submissive status following repeated intruder
      exposure. Behavioural status correlated with an increase in corticosterone and
      pro-inflammatory cytokines in both acute and chronic submissive groups. Mice from
      both status groups had body weight loss coupled with mild damage to the colon.
      Together these data show that short-term social interaction stress exposure was
      able to induce behavioural and physiological impairments similar to that observed
      in patients with dysregulated brain-gut axis function. Moreover, these data
      demonstrate that social stress-based mouse models may be appropriate for
      interrogating the mechanisms underlying such disorders.

PMID- 20826189
TI  - rDNA-targeted PCR primers and FISH probe in the detection of Ophiocordyceps
      sinensis hyphae and conidia.
AB  - Ophiocordyceps sinensis (Berk.) Sung, Sung, Hywel-Jones & Spatafora (syn.
      Cordyceps sinensis) one of the entomopathogenic fungi, is a rare Traditional
      Chinese Medicine (TCM) found in the Qinghai-Tibetan Plateau. Polymerase Chain
      Reaction (PCR) and Fluorescence in situ hybridization (FISH) methods are
      necessary to identify the mycelia or spores of O. sinensis from its habitat and
      to monitor its dispersal, colonization and infectivity. To develop both primers
      and probe specific to O. sinensis, ribosomal DNA (rDNA) amplified with universal
      primers from O. sinensis genomic DNA and seven closely related fungi were
      sequenced. According to these sequences, the upper and lower primers (OsT-F and
      OsT-R) were designed within internal transcribed spacer region 1 (ITS1) and ITS2
      and flanked by universal primers ITS5 and ITS4, respectively. The designed
      primers were used for general PCR, touchdown PCR, or both together with the
      universal primers for nested-touchdown PCR. The results showed that only the
      extracted DNA of O. sinensis was specifically amplified. The sensitivity of
      nested-touchdown PCR with extracted DNA of O. sinensis is as low as 10(-14)g (10
      fg) and at least 1000 times higher than the other PCR methods. In addition, Cy5
      labeled probe (OsLSU) for cytoplasmic LSU rRNA was hybridized with the ascospores
      of O. sinensis. It showed a strong red fluorescence throughout the whole cell but
      did not cross-react with other entomopathogenic fungi. Taken together, these
      methods were useful for studying the biology and ecology of O. sinensis.

PMID- 20826190
TI  - Quantitative in vitro assay to evaluate the capability of yeast cell wall
      fractions from Trichosporon mycotoxinivorans to selectively bind gram negative
      pathogens.
AB  - Yeast cell wall fractions have been proposed to bind enteropathogenic bacteria.
      The aim of this study was to develop a quantitative assay by measuring the
      optical density as growth parameter of adhering bacteria. The exponential growth
      phase of adhering bacteria was determined by optical density reading and compared
      with the colony count (CFU/mL). A linear regression was compiled and the
      bacterial number bound to the yeast cell wall product could be determined.
      Further focus was the investigation of a yeast cell wall from strain Trichosporon
      mycotoxinivorans (MTV) for its ability to bind gram negative Salmonella, E. coli
      and Campylobacter strains and gram positive probiotic bacteria of the genera
      lactobacilli and bifidobacteria as well as gram positive Clostridium perfringens
      quantitatively. The gram negative probiotic strain E. coli Nissle 1917 was also
      investigated. Seven out of 10 S. Typhimurium and S. Enteritidis strains adhered
      to the cell wall product with an amount between 10(3) and 10(4) CFU/10 MUg. Four
      out of 7 E. coli strains showed an average binding capability (10(2) CFU/10 ug)
      whereas 4*10(3) E. coli F4 cells bound per 10 MUg yeast cell wall. E. coli 0149
      K91, E. coli 0147 K89, C. jejuni and C. perfringens as well the genera
      lactobacilli and bifidobacteria did not bind to the yeast cell wall. E. coli
      Nissle 1917 was bound with 2*10(2) CFU/10 MUg. These results demonstrate that
      cell wall from MTV can be used to differentially bind E. coli spp. and Salmonella
      spp. up to 8*10(4) CFU/10 MUg. Thus certain yeast cell walls may prevent enteric
      infections caused by selective bacteria. This methodical approach would be an
      accurate tool in the feed industry for quality control of yeast cell wall
      products.

PMID- 20826191
TI  - Development of SCAR markers and PCR assays for single or simultaneous species
      specific detection of Phytophthora nicotianae and Pythium helicoides in ebb-and
      flow irrigated kalanchoe.
AB  - Phytophthora nicotianae and Pythium helicoides are important water-borne oomycete
      pathogens of irrigated ornamentals particularly ebb-and-flow irrigated kalanchoe
      in Japan. We developed novel PCR-based sequence characterized amplified region
      markers and assays for rapid identification and species-specific detection of
      both pathogens in separate PCR reactions or simultaneously in a duplex PCR.

PMID- 20826192
TI  - Recontouring teeth and closing diastemas with direct composite buildups: a
      clinical evaluation of survival and quality parameters.
AB  - OBJECTIVES: Irregular tooth shape and position in the anterior maxilla and
      mandible are major aesthetic problems for patients. In recent years such
      conditions have increasingly been treated minimally or even non-invasively by
      recontouring teeth with direct composite resin buildups. Although clinical
      experience with this treatment option is promising, evidence-based data about
      longevity are limited. METHODS: The authors evaluated survival and quality of 327
      composite buildups that were placed in 101 patients in the Department of
      Conservative Dentistry, University of Heidelberg, between 2002 and 2008. Follow
      up intervals and failures were recorded. Quality was assessed by grading
      restorations (modified USPHS/Ryge critera) still in situ without adverse event
      during the follow-up period. RESULTS: After a mean follow-up interval of 27.8
      months, 284 restorations were in situ and had no event. Forty-two restorations
      were in situ but had events that were mostly minor fractures of the composite
      resin. One restoration had been lost. Analysis of the time from insertion to any
      event or end of follow-up yielded an estimated 5-year survival rate of 79.2% (95%
      CI, 70.5-87.9). Quality was assessed by grading in situ restorations without
      event. More than 90% of graded restorations were categorized as "clinically
      excellent" (1) or "clinically good" (2). A correlation between those rated
      "clinically sufficient" or worse (>=3) and the follow-up period was observed.
      CONCLUSIONS: Direct composite buildups are aesthetic, functional, and
      biologically sound treatment options for recontouring teeth and closing diastemas
      with clinically promising survival rates. Therefore, tooth shape correction can
      be recommended in cases in which minimally invasive or non-invasive procedures on
      healthy teeth are indicated.

PMID- 20826194
TI  - A complex vector space model of single neuronal coding and experience.
AB  - A model of consciousness is proposed, in which the experience attributable to a
      single sensory neuron is related to its instantaneous firing rate. In that this
      can only be quantified within statistical limits from the incidence of spikes
      across multiple presentations of a stimulus, consciousness remains inaccessible
      to direct measurement on a single trial. In this way, the model disambiguates
      subjective experience from objective neural properties. The model adopts a
      quantum mechanical formalism, in which the state of the neuron is represented as
      a vector in a complex vector space.

PMID- 20826195
TI  - Overview: early history of crop growth and photosynthesis modeling.
AB  - As in industrial and engineering systems, there is a need to quantitatively study
      and analyze the many constituents of complex natural biological systems as well
      as agro-ecosystems via research-based mechanistic modeling. This objective is
      normally addressed by developing mathematically built descriptions of multilevel
      biological processes to provide biologists a means to integrate quantitatively
      experimental research findings that might lead to a better understanding of the
      whole systems and their interactions with surrounding environments. Aided with
      the power of computational capacities associated with computer technology then
      available, pioneering cropping systems simulations took place in the second half
      of the 20th century by several research groups across continents. This overview
      summarizes that initial pioneering effort made to simulate plant growth and
      photosynthesis of crop canopies, focusing on the discovery of gaps that exist in
      the current scientific knowledge. Examples are given for those gaps where
      experimental research was needed to improve the validity and application of the
      constructed models, so that their benefit to mankind was enhanced. Such research
      necessitates close collaboration among experimentalists and model builders while
      adopting a multidisciplinary/inter-institutional approach.

PMID- 20826193
TI  - Inhibition of the redox function of APE1/Ref-1 in myeloid leukemia cell lines
      results in a hypersensitive response to retinoic acid-induced differentiation and
      apoptosis.
AB  - OBJECTIVE: The standard of care for promyelocytic leukemia includes use of the
      differentiating agent all-trans retinoic acid (RA) and chemotherapy. RA induces
      cell differentiation through retinoic acid receptor (RAR) transcription factors.
      Because redox mechanisms influence how readily transcription factors bind to DNA
      response elements (RARE), the impact of small molecule (E3330) inhibition of the
      redox regulatory protein, apurinic-apyrimidinic endonuclease/redox effector
      factor (APE1/Ref-1) on RAR DNA binding and function in RA-induced myeloid
      leukemia cell differentiation and apoptosis was investigated. MATERIALS AND
      METHODS: The redox function of APE1 was studied using the small molecule
      inhibitor E3330 in HL-60 and PLB acute myeloid leukemia cells. Electrophoretic
      mobility shift assays were employed to determine effect of inhibitor on APE1/Ref
      1 redox signaling function. Trypan blue assays, Annexin-V/propidium iodide and
      CD11b staining, and real-time polymerase chain reaction analyses were employed to
      determine survival, apoptosis, and differentiation status of cells in culture.
      RESULTS: RARalpha binds to its RARE in a redox-dependent manner mediated by
      APE1/Ref-1 redox regulation. Redox-dependent RAR-RARE binding is blocked by
      E3330, a small molecule redox inhibitor of APE1/Ref-1. Combination treatment of
      RA + E3330 results in a profound hypersensitivity of myeloid leukemia cells to RA
      induced differentiation and apoptosis. Additionally, redox inhibition by E3330
      results in enhanced RAR target gene, BLR-1, expression in myeloid leukemia cells.
      CONCLUSIONS: The redox function of APE1/Ref-1 regulates RAR binding to its DNA
      RAREs influencing the response of myeloid leukemia cells to RA-induced
      differentiation. Targeting of APE1/Ref-1 redox function may allow manipulation of
      the retinoid response with therapeutic implications.

PMID- 20826196
TI  - beta-Amyloid precursor protein and tau protein levels are differently regulated
      in human cerebellum compared to brain regions vulnerable to Alzheimer's type
      neurodegeneration.
AB  - It is well established that the human brain exhibits regional variability in its
      vulnerability to Alzheimer's disease (AD) pathology. We set out to determine if
      this regional vulnerability is reflected in the expression pattern, or
      processing, of two key proteins involved in AD pathology, the beta-amyloid
      precursor protein (APP) and tau, by immunoblotting. Our data demonstrate that APP
      processing and APP protein levels are not different between AD patients and
      healthy, age-matched subjects, but that levels of mature APP are greatly reduced
      in cerebellum compared to regions of the brain most vulnerable to AD, entorhinal
      cortex and hippocampus. In addition, protein levels of tau are significantly
      reduced in cerebellum compared to all other human brain regions examined.
      Unexpectedly, protein levels of glycogen synthase kinase 3 (GSK3), a major tau
      kinase, are at their lowest in hippocampus. The observations demonstrate that
      both mature APP as well as total APP and tau protein levels are greatly reduced
      in human cerebellum, a region of the human brain most resistant to AD pathology.

PMID- 20826197
TI  - Variations of the CAG trinucleotide repeat in DNA polymerase gamma (POLG1) is
      associated with Parkinson's disease in Sweden.
AB  - DNA polymerase gamma (POLG1) is coding for the catalytic subunit of the
      heterotrimeric mitochondrial DNA polymerase and involved in replication and
      repair of mitochondrial DNA. In addition to its 5' to 3' polymerase activity,
      POLG1 has a 3' to 5' exonuclease activity important in the repair process.
      Mitochondrial dysfunction has been implicated in neurodegenerative disorders like
      Parkinson's disease (PD). Dopamine neurons, which degenerate in PD, are believed
      to be particularly susceptible to mitochondrial dysfunction, which makes POLG1 a
      possible candidate gene for the disease. POLG1 has a polyglutamine tract (poly-Q)
      in the N-terminal, encoded by a CAG sequence in exon 2. Most commonly the poly-Q
      tract comprises 10 repeats (10Q, frequency >80%) or moderately common 11Q
      (frequency 6-12%); however the composition of poly-Q alleles has been reported to
      vary from 6Q to 14Q. We analyzed this POLG1 trinucleotide repeat in a Swedish PD
      case-control material and detected variations from 5Q to 15Q. We report a
      significant association between the non-10/11Q repeats with PD (p=0.002). In
      silico analysis of poly-Q length effect on mRNA folding energy show a decrease in
      energy for <10/11Q mRNA (4.6%) and an increase for >10/11Q mRNA (4.8%) compared
      to 10/11Q mRNA. Our results strengthen the evidence for involvement of POLG1 and
      mitochondrial dysfunction in PD.

PMID- 20826198
TI  - Botulinum neurotoxin type A counteracts neuropathic pain and facilitates
      functional recovery after peripheral nerve injury in animal models.
AB  - A growing interest was recently focused on the use of Botulinum neurotoxin
      serotype A (BoNT/A) for fighting pain. The aim of this study was to investigate
      the effects of BoNT/A on neuropathic pain. It was observed that BoNT/A is able to
      counteract neuropathic pain induced by chronic constriction injury (CCI) to the
      sciatic nerve both in mice and in rats. This effect is already present after a
      single intraplantar (i.pl.) or intrathecal (i.t.) neurotoxin administration that
      significantly reduces the sciatic nerve ligation-induced mechanical allodynia in
      mice and rats and thermal hyperalgesia in rats. This effect was evident starting
      24 h after the administration of BoNT/A and it was long-lasting, being present 81
      or 25 days after i.pl. injection of the higher dose in mice (15 pg/paw) and rats
      (75 pg/paw), respectively, and 35 days after i.t. injection in rats (75 pg/rat).
      Moreover, BoNT/A-injected mice showed a quicker recovery of the walking pattern
      and weight bearing compared to control groups. The behavioral improvement was
      accompanied by structural modifications, as revealed by the expression of cell
      division cycle 2 (Cdc2) and growth associated protein 43 (GAP-43) regeneration
      associated proteins, investigated by immunofluorescence and Western blotting in
      the sciatic nerve, and by the immunofluorescence expression of S100beta and glial
      fibrillary acidic protein (GFAP) Schwann cells proteins. In conclusion, the
      present research demonstrate long-lasting anti-allodynic and anti-hyperalgesic
      effects of BoNT/A in animal models of neuropathic pain together with an
      acceleration of regenerative processes in the injured nerve, as evidenced by both
      behavioral and immunohistochemistry/blotting analysis. These results may have
      important implications in the therapy of neuropathic pain.

PMID- 20826199
TI  - Activation of phosphatidylinositol 3-kinase/Akt-mammalian target of Rapamycin
      signaling pathway in the hippocampus is essential for the acquisition of morphine
      induced place preference in rats.
AB  - Hippocampus is a critical structure for the acquisition of morphine-induced
      conditioned place preference (CPP), which is a usual learning paradigm for
      assessing drug reward. However, the precise mechanisms remain largely unknown.
      Phosphatidylinositol 3-kinase (PI3K) and its downstream targets, including Akt,
      mammalian target of Rapamycin (mTOR) and 70-kDa ribosomal S6 kinase (p70S6K), are
      critical molecules implicated in learning and memory. Here, we tested the role of
      PI3K/Akt-mTOR-p70S6K signaling pathway in morphine-induced CPP in the
      hippocampus. Our results showed that the acquisition of morphine CPP increased
      phosphorylation of Akt in the hippocampal CA3, but not in the nucleus accumbens
      (NAc), the ventral tegmental area (VTA) or the CA1. Moreover, the phosphorylated
      Akt exclusively expressed in the CA3 neurons. Likewise, levels of phosphorylated
      mTOR and p70S6K were significantly enhanced in the CA3 following morphine CPP.
      The alterations of these phosphorylated proteins are positively correlated with
      the acquisition of morphine CPP. More importantly, microinjection of PI3K
      inhibitor (LY294002) or mTOR inhibitor (Rapamycin) into the CA3 prevented the
      acquisition of CPP and inhibited the activation of PI3K-Akt signaling pathway. In
      addition, pre-infusion of beta-FNA (beta-funaltrexamine hydrochloride), a
      selective irreversible MU opioid receptor antagonist, into CA3 significantly
      prevented the acquisition of CPP and impaired Akt phosphorylation. All these
      results strongly implied that the PI3K-Akt signaling pathway activated by MU
      opioid receptor in hippocampal CA3 plays an important role in acquisition of
      morphine-induced CPP.

PMID- 20826200
TI  - Differential involvement of medial prefrontal cortex and basolateral amygdala
      extracellular signal-regulated kinase in extinction of conditioned taste aversion
      is dependent on different intervals of extinction following conditioning.
AB  - Extinction reflects a decrease in the conditioned response (CR) following non
      reinforcement of a conditioned stimulus. Behavioral evidence indicates that
      extinction involves an inhibitory learning mechanism in which the extinguished CR
      reappears with presentation of an unconditioned stimulus. However, recent studies
      on fear conditioning suggest that extinction erases the original conditioning if
      the time interval between fear acquisition and extinction is short. The present
      study examined the effects of different intervals between acquisition and
      extinction of the original memory in conditioned taste aversion (CTA). Male Long
      Evans rats acquired CTA by associating a 0.2% sucrose solution with malaise
      induced by i.p. injection of 4 ml/kg 0.15 M LiCl. Two different time intervals, 5
      and 24 h, between CTA acquisition and extinction were used. Five or 24 h after
      CTA acquisition, extinction trials were performed, in which a bottle containing
      20 ml of a 0.2% sucrose solution was provided for 10 min without subsequent LiCl
      injection. If sucrose consumption during the extinction trials was greater than
      the average water consumption, then rats were considered to have reached CTA
      extinction. Rats subjected to extinction trials lasting 24 h, but not 5 h, after
      acquisition re-exhibited the extinguished CR following injection of 0.15 M LiCl
      alone 7 days after acquisition. Extracellular signal-regulated kinase (ERK) in
      the medial prefrontal cortex (mPFC) and basolateral nucleus of the amygdala (BLA)
      was examined by Western blot after the first extinction trial. ERK activation in
      the mPFC was induced after the extinction trial beginning 5 h after acquisition,
      whereas the extinction trial performed 24 h after acquisition induced ERK
      activation in the BLA. These data suggest that the original conditioning can be
      inhibited or retained by CTA extinction depending on the time interval between
      acquisition and extinction and that the ERK transduction pathway in the mPFC and
      BLA is differentially involved in these processes.

PMID- 20826201
TI  - Development of a novel combination tablet containing trimebutine maleate and
      mosapride citrate for the treatment of functional dyspepsia.
AB  - To develop a novel combination tablet which contained 100 mg trimebutine maleate
      and 5 mg mosapride citrate (TMCT) for the treatment of functional dyspepsia, the
      wet granulation method was used to prepare TMCTs with various amounts of diluents
      and stabilizers. The levels of impurities, the stability and the dissolution of
      the TMCTs were investigated. The oral bioavailability of drugs in the TMCTs was
      then evaluated and compared to the simultaneous oral administration of
      trimebutine maleate-loaded and mosapride citrate-loaded commercial products in
      the beagle dog. Among the diluents tested, D-mannitol was selected, since the
      microcrystalline cellulose and lactose did not inhibit the production of drug
      impurities due to their hygroscopic properties and chemical interactions,
      respectively. Furthermore, succinic acid was selected as the stabilizer because
      it gave the lowest level of total drug impurities of the organic acids tested.
      The combination tablet of trimebutine maleate and mosapride citrate prepared with
      D-mannitol and succinic acid gave a total drug content higher than 95% and total
      impurities lower than 0.5% at 25 degrees C/60% RH and 40 degrees C/75% RH during
      a 6-month period, indicating that the tablets were stable for at least 6 months.
      Furthermore, this combination tablet showed a similar dissolution to the
      trimebutine maleate-loaded and mosapride citrate-loaded commercial products and
      gave insignificantly different absorption compared to these commercial products
      in beagle dogs. Thus, the combination tablet of trimebutine maleate and mosapride
      citrate prepared with D-mannitol and succinic acid would be a stable and
      effective oral pharmaceutical product for the treatment of functional dyspepsia.

PMID- 20826202
TI  - Isosorbide-5-mononitrate (5-ISMN) sustained-release pellets prepared by double
      layer coating for reducing 5-ISMN migration and sublimation.
AB  - The major aim of this study was to prepare isosorbide-5-mononitrate (5-ISMN)
      sustained-release pellets and evaluate their stability. The pellets were prepared
      by extrusion/spheronization, and then the core pellets were coated with
      ethylcellulose (EC 10cp) and Eudragit((r))NE30D. Here, EC was used as the
      subcoating agent while Eudragit((r))NE30D acted as the outer-coating agent. 5
      ISMN sustained-release pellets as a novel drug delivery system contained the
      immediate-release portion in the outer-coating layer. Unexpectedly, 5-ISMN was
      found to migrate from the interior of the pellets to the surface forming needle
      crystals and exhibited the phenomenon of sublimation, which resulted in a
      tremendous increase in the release rate. Our research showed that the migration
      and sublimation of the active ingredient was related to the temperature and
      humidity. Polyvinylpyrrolidone (PVP K30) can affect the precipitation of 5-ISMN
      by forming a charge transfer complex between the drug and PVP, while
      hydroxypropyl methyl cellulose (HPMC E5) had no effect, and confirmed the
      correctness of this view through photographs and IR spectra. In the investigation
      of the stability, the results showed that there was no sublimation and migration
      while the pellets stored at 25 degrees C/60%RH (ambient conditions) and 40
      degrees C/75% RH (stress conditions) during a 6-month period.

PMID- 20826203
TI  - Salicylate restores transport function and anion exchanger activity of missense
      pendrin mutations.
AB  - The SLC26A4 gene encodes the transmembrane protein pendrin, which is involved in
      the homeostasis of the ion concentration of the endolymph of the inner ear, most
      likely by acting as a chloride/bicarbonate transporter. Mutations in the SLC26A4
      gene cause sensorineuronal hearing loss. However, the mechanisms responsible for
      such loss have remained unknown. Therefore, in this study, we focused on the
      function of ten missense pendrin mutations (p.P123S (Pendred syndrome), p.M147V
      (NSEVA), p.K369E (NSEVA), p.A372V (Pendred syndrome/NSEVA), p.N392Y (Pendred
      syndrome), p.C565Y (NSEVA), p.S657N (NSEVA), p.S666F (NSEVA), p.T721M (NSEVA) and
      p.H723R (Pendred syndrome/NSEVA)) reported in Japanese patients, and analyzed
      their cellular localization and anion exchanger activity using HEK293 cells
      transfected with each mutant gene. Immunofluorescent staining of the cellular
      localization of the pendrin mutants revealed that p.K369E and p.C565Y, as well as
      wild-type pendrin, were transported to the plasma membrane, while 8 other mutants
      were retained in the cytoplasm. Furthermore, we analyzed whether salicylate, as a
      pharmacological chaperone, restores normal plasma membrane localization of 8
      pendrin mutants retained in the cytoplasm to the plasma membrane. Incubation with
      10 mM of salicylate of the cells transfected with the mutants induced the
      transport of 4 pendrin mutants (p.P123S, p.M147V, p.S657Y and p.H723R) from the
      cytoplasm to the plasma membrane and restored the anion exchanger activity. These
      findings suggest that salicylate might contribute to development of a new method
      of medical treatment for sensorineuronal hearing loss caused by the mutation of
      the deafness-related proteins, including pendrin.

PMID- 20826204
TI  - Antiplasmodial activity of aporphine alkaloids and sesquiterpene lactones from
      Liriodendron tulipifera L.
AB  - AIM OF THE STUDY: The objective of this study was to isolate and characterize the
      active constituents of the traditionally used antimalarial plant Liriodendron
      tulipifera by antiplasmodial-assay guided fractionation. MATERIALS AND METHODS:
      Bark and leaves were extracted with solvents of increasing polarity. Fractions
      were generated using flash chromatography, counter current chromatography and
      preparative HPLC and subjected to in vitro antiplasmodial and cytotoxicity
      assays. Active fractions were subjected to further fractionation until pure
      compounds were isolated, for which the IC(50) values were calculated. RESULTS AND
      DISCUSSION: Six known aporphine alkaloids, asimilobine (1), norushinsunine (2),
      norglaucine (3), liriodenine (4), anonaine (5) and oxoglaucine (6) were found to
      be responsible for the antiplasmodial activity of the bark. Leaves yielded two
      known sesquiterpene lactones, peroxyferolide (7) and lipiferolide (8) with
      antiplasmodial activity. The antiplasmodial activity of (2) (IC(50)=29.6 MUg/mL),
      (3) (IC(50)=22.0 MUg/mL), (6) (IC(50)=9.1 MUg/mL), (7) (IC(50)=6.2 MUg/mL) and
      (8) (IC(50)=1.8 MUg/mL) are reported for the first time. CONCLUSION: This work
      supports the historical use of Liriodendron tulipifera as an antimalarial remedy
      of the United States and characterizes its antiplasmodial constituents.

PMID- 20826205
TI  - Invasion of Burkholderia cepacia complex isolates into lung epithelial cells
      involves glycolipid receptors.
AB  - Burkholderia cepacia complex (Bcc) is a group of opportunistic cystic fibrosis
      (CF) pathogens that invade lung epithelial cells. The mechanisms of invasion are
      poorly understood, in particular, the receptors utilised by this bacterium in the
      invasion process have not been identified. The aim of this study was to
      investigate the epithelial receptors involved in the invasion of Bcc isolates. We
      confirmed that invasion into two lung epithelial cell lines (16HBE14o- and
      CFBE41o-) which have a non-CF and CF phenotype, respectively, is receptor
      mediated and showed that pre-treatment of these epithelial cell lines with alpha-
      or beta-galactosidase reduced invasion of isolates of two species of Bcc,
      Burkholderia multivorans and Burkholderia cenocepacia. In contrast, removal of
      mucin had no significant effect. Biotinylated Bcc strains were shown to bind to
      purified glycolipids separated by thin layer chromatography, albeit different
      patterns of binding were associated with different strains. Invasion of CF lung
      epithelial cells (CFBE41o-) by all three Bcc strains examined was significantly
      reduced by treatment of cells with inhibitors of glycolipid biosynthesis.
      Although the specific glycolipid involved in each case has not been elucidated,
      it is apparent that invasion of lung epithelial cells is mediated via binding to
      glycosphingolipid receptors.

PMID- 20826206
TI  - Genome-wide analysis of the cis-regulatory modules of divergent gene pairs in
      yeast.
AB  - In budding yeast, approximately a quarter of adjacent genes are divergently
      transcribed (divergent gene pairs). Whether genes in a divergent pair share the
      same regulatory system is still unknown. By examining transcription factor (TF)
      knockout experiments, we found that most TF knockout only altered the expression
      of one gene in a divergent pair. This prompted us to conduct a comprehensive
      analysis in silico to estimate how many divergent pairs are regulated by common
      sets of TFs (cis-regulatory modules, CRMs) using TF binding sites and expression
      data. Analyses of ten expression datasets show that only a limited number of
      divergent gene pairs share CRMs in any single dataset. However, around half of
      divergent pairs do share a regulatory system in at least one dataset. Our
      analysis suggests that genes in a divergent pair tend to be co-regulated in at
      least one condition; however, in most conditions, they may not be co-regulated.

PMID- 20826207
TI  - Consequences of ionizing radiation-induced damage in human neural stem cells.
AB  - Cranial irradiation remains a frontline treatment for brain cancer, but also
      leads to normal tissue damage. Although low-dose irradiation (<=10 Gy) causes
      minimal histopathologic change, it can elicit variable degrees of cognitive
      dysfunction that are associated with the depletion of neural stem cells. To
      decipher the mechanisms underlying radiation-induced stem cell dysfunction, human
      neural stem cells (hNSCs) subjected to clinically relevant irradiation (0-5 Gy)
      were analyzed for survival parameters, cell-cycle alterations, DNA damage and
      repair, and oxidative stress. hNSCs showed a marked sensitivity to low-dose
      irradiation that was in part due to elevated apoptosis and the inhibition of cell
      cycle progression that manifested as a G2/M checkpoint delay. Efficient removal
      of DNA double-strand breaks was indicated by the disappearance of gamma-H2AX
      nuclear foci. A dose-responsive and persistent increase in oxidative and
      nitrosative stress was found in irradiated hNSCs, possibly the result of a higher
      metabolic activity in the fraction of surviving cells. These data highlight the
      marked sensitivity of hNSCs to low-dose irradiation and suggest that long-lasting
      perturbations in the CNS microenvironment due to radiation-induced oxidative
      stress can compromise the functionality of neural stem cells.

PMID- 20826208
TI  - Skin cell protection against UVA by Sideroxyl, a new antioxidant complementary to
      sunscreens.
AB  - Oxidative stress resulting from photosensitized ROS production in skin is widely
      accepted as the main contributor to the deleterious effects of UVA exposure.
      Among the mechanisms known to be involved in UVA-induced oxidative damage, iron
      plays a central role. UVA radiation of skin cells induces an immediate release of
      iron, which can then act as a catalyst for uncontrolled oxidation reactions of
      cell components. Such site-specific damage can scarcely be counteracted by
      classical antioxidants. In contrast, iron chelators potentially offer an
      effective way to protect skin against UVA insults. However, iron chelation is
      very difficult to achieve without disturbing iron homeostasis or inducing iron
      depletion. A novel compound was developed to avoid these potentially harmful side
      effects. Sideroxyl was designed to acquire its strong chelating capability only
      during oxidative stress according to an original process of intramolecular
      hydroxylation. Herein, we describe in vitro results demonstrating the protective
      efficiency of Sideroxyl against deleterious effects of UVA at the molecular,
      cellular, and tissular levels. First, the Sideroxyl diacid form protects a model
      protein against UVA-induced photosensitized carbonylation. Second, intracellular
      ROS are dose-dependently decreased in the presence of Sideroxyl in both human
      cultured fibroblasts and human keratinocytes. Third, Sideroxyl protects normal
      human fibroblasts against UVA-induced DNA damage as measured by the comet assay
      and MMP-1 production. Finally, Sideroxyl provides protection against UVA-induced
      alterations in human reconstructed skin. These results suggest that Sideroxyl may
      prevent UVA-induced damage in human skin as a complement to sunscreens,
      especially in the long-wavelength UVA range.

PMID- 20826210
TI  - Characterization of Kunitz-type protease inhibitor purified from hemolymph of
      Galleria mellonella larvae.
AB  - We characterized a Kunitz-type protease inhibitor (Gm KTPI) obtained from the
      hemolymph of Galleria mellonella larvae immunized with Escherichia coli. The
      structural analysis of the cloned cDNA showed that it consists of 56 residues
      derived from the precursor of 75 amino acids. The peptide was constitutively
      produced in the fat bodies, but not in the midgut nor the integument of larvae.
      In our analysis of stage-dependent expression, its transcript was detected within
      the midgut, the fat bodies and the integument of the prepupae, which undergo
      tissue remodeling. The inhibition assays showed that Gm KTPI was capable of
      inhibiting only the trypsin-like activity of the larval midgut extracts.
      Furthermore, it was determined that Gm KTPI induced the activation of
      extracellular signal-regulated kinase (ERK) in the fat bodies and integument
      cells, and this kinase is known to perform a central role in cell proliferation
      signaling. Its effect on ERK activation was also verified in a control experiment
      using a human endothelial cell culture. Collectively, it was suggested that Gm
      KTPI might be responsible for the protection of other tissues against proteolytic
      attack by trypsin-like protease(s) from larval midgut during metamorphosis, and
      might play a role in the proliferation of cells in the fat body and integument.

PMID- 20826211
TI  - Insecticidal properties of Sclerotinia sclerotiorum agglutinin and its
      interaction with insect tissues and cells.
AB  - This project studied in detail the insecticidal activity of a fungal lectin from
      the sclerotes of Sclerotinia sclerotiorum, referred to as S. sclerotiorum
      agglutinin or SSA. Feeding assays with the pea aphid (Acyrthosiphon pisum) on an
      artificial diet containing different concentrations of SSA demonstrated a high
      mortality caused by this fungal lectin with a median insect toxicity value (LC50)
      of 66 (49-88) MUg/ml. In an attempt to unravel the mode of action of SSA the
      binding and interaction of the lectin with insect tissues and cells were
      investigated. Histofluorescence studies on sections from aphids fed on an
      artificial liquid diet containing FITC-labeled SSA, indicated the insect midgut
      with its brush border zone as the primary target for SSA. In addition, exposure
      of insect midgut CF-203 cells to 25 MUg/ml SSA resulted in a total loss of cell
      viability, the median cell toxicity value (EC50) being 4.0 (2.4-6.7) MUg/ml.
      Interestingly, cell death was accompanied with DNA fragmentation, but the effect
      was caspase-3 independent. Analyses using fluorescence confocal microscopy
      demonstrated that FITC-labeled SSA was not internalized in the insect midgut
      cells, but bound to the cell surface. Prior incubation of the cells with saponin
      to achieve a higher cell membrane permeation resulted in an increased
      internalization of SSA in the insect midgut cells, but no increase in cell
      toxicity. Furthermore, since the toxicity of SSA for CF-203 cells was
      significantly reduced when SSA was incubated with GalNAc and asialomucin prior to
      treatment of the cells, the data of this project provide strong evidence that SSA
      binds with specific carbohydrate moieties on the cell membrane proteins to start
      a signaling transduction cascade leading to death of the midgut epithelial cells,
      which in turn results in insect mortality. The potential use of SSA in insect
      control is discussed.

PMID- 20826209
TI  - Prenatal cocaine exposure, gender, and adolescent stress response: a prospective
      longitudinal study.
AB  - Prenatal cocaine exposure is associated with alterations in arousal regulation in
      response to stress in young children. However, relations between cocaine exposure
      and stress response in adolescence have not been examined. We examined salivary
      cortisol, self-reported emotion, heart rate, and blood pressure (BP) responses to
      the Trier Social Stress Test (TSST) in 49 prenatally cocaine and other drug
      exposed (PCE) and 33 non-cocaine-exposed (NCE) adolescents. PCE adolescents had
      higher cortisol levels before and after stress exposure than NCE adolescents. PCE
      girls showed an elevated anxiety response to stress (compared to NCE girls) and
      PCE boys showed a dampened diastolic BP response (compared to NCE boys). Girls
      showed higher anger response and lower pre-stress systolic BP than boys. Group
      differences were found controlling for potential confounding variables and were
      not moderated by caregiver-child relationship quality (although relationship
      quality predicted HPA axis and anxiety response). The findings suggest that
      prenatal drug exposure is associated with altered stress response in adolescence
      and that gender moderates this association.

PMID- 20826212
TI  - The dominant-STN phenomenon in bilateral STN DBS for Parkinson's disease.
AB  - In some patients with Parkinson's disease (PD) and bilateral STN-DBS the motor
      benefit from one STN alone appears similar to the improvement obtained with
      bilateral STN-DBS. Thus, we hypothesized that some patients have a "dominant
      STN," whose stimulation achieves similar results than bilateral stimulation.
      Twenty-two consecutive PD patients with bilateral STN-DBS were assessed in 4
      randomized conditions: bilateral off-stimulation, bilateral on-stimulation,
      unilateral right- and unilateral left-stimulation. A hierarchical agglomerative
      cluster analysis of the motor UPDRS scores in these 4 conditions showed that 11
      patients (50%) presented with a "dominant-STN." Interestingly, in 3 of these
      patients the dominant-STN was ipsilateral to the most affected side of the body.
      Our results support the presence of different phenotypes of response to bilateral
      STN stimulation. In our sample 50% of the patients presented with a dominant-STN,
      suggesting that a non-negligible part of PD patients might not need bilateral STN
      DBS surgery.

PMID- 20826213
TI  - Endothelin modulates the cardiovascular effects of clonidine in the rat.
AB  - Clonidine decreases mean arterial pressure (MAP) by acting as an alpha(2)
      adrenergic receptor (AR) agonist in the central nervous system; it also acts on
      peripheral alpha-ARs to produce vasoconstriction. Endothelin (ET) has been shown
      to modulate the action of ARs. The present study was conducted to determine the
      involvement of ET in cardiovascular effects of clonidine. Intravenous
      administration of clonidine (10, 30 and 90MUgkg(-1)) produced a dose-dependent
      decrease in MAP and heart rate (HR). Treatment with ET-1 (100, 300 and 900ngkg(
      1)) significantly attenuated clonidine (10MUgkg(-1)) induced fall in MAP and HR.
      Rats treated with ET-1 (900ngkg(-1)) showed an increase in MAP and HR after
      clonidine administration compared to untreated rats, while ET(A/B) antagonist,
      TAK-044 (1mgkg(-1)) and ET(A) antagonist, BMS-182874 (9mgkg(-1)) potentiated the
      hypotensive effect of clonidine. ET(B) receptor agonist, IRL-1620 (5MUgkg(-1))
      produced significant attenuation of clonidine induced fall in MAP and HR, while
      ET(B) receptor antagonist, BQ-788 (0.3mgkg(-1)), potentiated the hypotensive
      effect of clonidine. Prazosin (0.1mgkg(-1)) completely blocked ET-1 induced
      changes in cardiovascular effects of clonidine. Clonidine-induced contraction of
      rat abdominal aortic ring was potentiated by ET-1, which was completely blocked
      by prazosin. Clonidine produced an increase in ET(A) receptor expression in the
      brain and abdominal aorta while ET(B) receptors were not affected. It is
      concluded that ET enhances the responsiveness of vascular ARs to the constrictor
      effect of clonidine and ET antagonists potentiate the hypotensive effect of
      clonidine suggesting that a combination of ET antagonist with clonidine may be a
      useful option to treat hypertension.

PMID- 20826214
TI  - Mycobacterium tuberculosis Rv1090 and Rv1987 encode functional beta-glucan
      targeting proteins.
AB  - Mycobacterium tuberculosis is a facultative intracellular pathogen, and the
      ability of this bacterium to survive and to grow inside macrophages is central to
      its virulence. Multiple strategies are employed by M. tuberculosis to ensure
      survival in macrophages, including secretion of several proteins, which are good
      candidates to be virulence factors, drug targets for disease intervention, and
      vaccine antigens. However, some M. tuberculosis secreted proteins do not appear
      to play any role in the growth or survival of the bacterium in its mammalian
      host. Among these proteins are three putative cellulose-targeting proteins
      encoded by the genes Rv0062, Rv1090, and Rv1987. It has been previously shown
      that Rv0062 encodes an active cellulase. Here we report that Rv1090 and Rv1987
      also encode functional proteins. Rv1090 is able to hydrolyze barley beta-glucan
      while Rv1987 displays cellulose-binding activity on filter paper and on
      microcrystalline cellulose (Avicel). Collectively, these observations point
      toward a unique unknown relationship between M. tuberculosis and a cellulose
      containing host. We hypothesize that amoeba could be such hosts.

PMID- 20826215
TI  - Prokaryotic expression, refolding, and purification of functional human vascular
      endothelial growth factor isoform 165: purification procedures and refolding
      conditions revisited.
AB  - Human vascular endothelial growth factor isoform 165 (VEGF165) is the first known
      member belonging to the VEGF protein family that plays a critical role in new
      blood vessel formation in vivo. This study presents a new protocol with optimized
      conditions for rapidly producing untagged recombinant and biological active human
      VEGF165 (rhVEGF165) using Escherichia coli cells. Protein was isolated from
      inclusion bodies, purified by gel filtration and ion exchange chromatography, and
      subjected to protein refolding and renaturation. The biological activity of
      rhVEGF165 is comparable with VEFG from eukaryotic source according to human
      umbilical vein endothelial cells (HUVEC) proliferation assay. Therefore, the
      present procedures provide a fast and easy way to produce this therapeutic
      protein.

PMID- 20826216
TI  - Functional comparison of recombinant acidic mammalian chitinase with enzyme from
      murine bronchoalveolar lavage.
AB  - Acidic mammalian chitinase (AMCase) is an enzyme that selectively degrades the
      biopolymer chitin. Several chitinase enzymes are utilized by mammals to hydrolyze
      chitin encountered by inhalation and ingestion. AMCase is distinct from other
      mammalian chitinases as its activity is retained in strongly acidic conditions
      (pH <2.0). AMCase expression is induced by antigen-induced mouse models of
      allergic lung inflammation. This protein has also been implicated in the
      pathogenesis of asthma although its precise role is poorly defined. We describe a
      novel way to express and purify active murine AMCase. This material retains
      properties observed in mouse bronchoalveolar lavage (BAL) fluid with regard to pH
      preference of activity and its inhibition by cyclic peptide inhibitors argifin
      and argadin. We found that chitinase in BAL from both antigen-challenged and
      control animals have similar properties in this regard. This strongly supports
      the notion the same enzyme (AMCase) gives rise to chitinase activity in both
      challenged and unchallenged animals. We also describe expression of active human
      AMCase. The methods described in this paper provide a reliable source of
      recombinant AMCase that can be utilized to expand understanding of AMCase's role
      in regulating allergic inflammation.

PMID- 20826217
TI  - Expression and characterization of the Neurospora crassa endoglucanase GH5-1.
AB  - Filamentous fungi secrete a wide range of enzymes, including cellulases and
      hemicellulases, with potential applications in the production of lignocellulosic
      biofuels. Of the cellulolytic fungi, Hypocrea jecorina (anamorph Trichoderma
      reesei) is the best characterized in terms of cellulose degradation, but other
      cellulolytic fungi, such as the model filamentous fungus Neurospora crassa, can
      serve a crucial role in building our knowledge about the fungal response to
      biomass due to the many molecular and genetic tools available for this organism.
      Here we cloned and expressed GH5-1 (NCU00762), a secreted endoglucanase in N.
      crassa. The protein was produced using a ccg-1 promoter under conditions in which
      no other cellulases are present. Native GH5-1 (nGH5-1) and this recombinant GH5-1
      (rGH5-1) were purified to gauge differences in glycosylation and activity; both
      rGH5-1 and nGH5-1 were similarly glycosylated, with an estimated molecular weight
      of 52kDa. On azo-carboxymethylcellulose, rGH5-1 activity was equal to that of
      nGH5-1, and on cellulose (Avicel) rGH5-1 was 20% more active. The activity of a
      GH5-1-GFP fusion protein (rGH5-1-GFP-6xHis) was similar to rGH5-1 and nGH5-1. To
      determine the binding pattern of catalytically active rGH5-1-GFP-6xHis to plant
      cell walls, Arabidopsis seedlings were incubated with rGH5-1-GFP-6xHis or
      Pontamine Fast Scarlet 4B (S4B), a cellulose-specific dye. Confocal microscopy
      showed that rGH5-1-GFP-6xHis bound in linear, longitudinal patterns on seedling
      roots, similar to S4B. The functional expression and characterization of rGH5-1
      and its GFP fusion derivative set important precedents for further investigation
      of biomass degradation by filamentous fungi, especially N. crassa, with
      applications for characterization and manipulation of novel enzymes.

PMID- 20826219
TI  - Knowing and working with Richard F. Thompson.
AB  - A few brief anecdotes are provided, relating to life in Richard Thompson's
      laboratory during the 1980s and 1990s.

PMID- 20826218
TI  - Cryo transmission X-ray imaging of the malaria parasite, P. falciparum.
AB  - Cryo transmission X-ray microscopy in the "water window" of photon energies has
      recently been introduced as a method that exploits the natural contrast of
      biological samples. We have used cryo tomographic X-ray imaging of the intra
      erythrocytic malaria parasite, Plasmodium falciparum, to undertake a survey of
      the cellular features of this important human pathogen. We examined whole
      hydrated cells at different stages of growth and defined some of the structures
      with different X-ray density, including the parasite nucleus, cytoplasm,
      digestive vacuole and the hemoglobin degradation product, hemozoin. As the
      parasite develops from an early cup-shaped morphology to a more rounded shape,
      puncta of hemozoin are formed; these coalesce in the mature trophozoite into a
      central compartment. In some trophozoite stage parasites we observed
      invaginations of the parasite surface and, using a selective permeabilization
      process, showed that these remain connected to the RBC cytoplasm. Some of these
      invaginations have large openings consistent with phagocytic structures and we
      observed independent endocytic vesicles in the parasite cytoplasm which appear to
      play a role in hemoglobin uptake. In schizont stage parasites staggered mitosis
      was observed and X-ray-dense lipid-rich structures were evident at their apical
      ends of the developing daughter cells. Treatment of parasites with the
      antimalarial drug artemisinin appears to affect parasite development and their
      ability to produce the hemoglobin breakdown product, hemozoin.

PMID- 20826220
TI  - Genetic analysis of mobile tetQ elements in oral Prevotella species.
AB  - Prevotella species are members of the bacterial oral flora and are opportunistic
      pathogens in polymicrobial infections of soft tissues. Antibiotic resistance to
      tetracyclines is common in these bacteria, and the gene encoding this resistance
      has been previously identified as tetQ. The tetQ gene is also found on
      conjugative transposons in the intestinal Bacteroides species; whether these
      related bacteria have transmitted tetQ to Prevotella is unknown. In this study,
      we describe our genetic analysis of mobile tetQ elements in oral Prevotella
      species. Our results indicate that the mobile elements encoding tetQ in oral
      species are distinct from those found in the Bacteroides. The intestinal bacteria
      may act as a reservoir for the tetQ gene, but Prevotella has incorporated this
      gene into an IS21-family transposon. This transposon is present in Prevotella
      species from more than one geographical location, implying that the mechanism of
      tetQ spread between oral Prevotella species is highly conserved.

PMID- 20826221
TI  - Residual yolk energetics and postnatal shell growth in Smooth Softshell Turtles,
      Apalone mutica.
AB  - We examined functions of residual yolk (RY) in hatchling Smooth Softshell Turtles
      (Apalone mutica). Removal of RY did not affect survival, shell growth, or resting
      metabolic rates of turtles for 40 d after hatching. Our estimates of metabolic
      rate suggest that RY can fuel maintenance and activity metabolism for
      approximately 25 days. A. mutica absorb more than 1g of water in the first 2
      weeks of life, which appears to be the basis of post-hatch shell expansion rather
      than yolk-provisioned growth. Post-hatch growth may be limited by the magnitude
      of RY remaining at hatching, but RY protein and lipid proportions do not differ
      from those of freshly-laid eggs. In addition, A. mutica did not use RY to fuel
      nest emergence. Our results suggest that RY does not fulfill several hypothetical
      functions in A. mutica, including postnatal growth, catabolic fuel for nest
      emergence, and long-term nutritional sustenance for maintenance, activity, or
      hibernation. Instead, A. mutica appear to absorb most yolk prior to hatching, and
      are left with a minimum of RY. Variation in RY mass with incubation regime in
      other species suggests that mothers may overprovision their eggs to ensure
      successful development across a diversity of possible incubation conditions.

PMID- 20826222
TI  - Feeding responses to central administration of several somatostatin analogs in
      chicks.
AB  - Somatostatin is well known as an inhibitor of growth hormone release from the
      anterior pituitary. Its effects are exerted via 5 subtypes of receptors, which
      are named SSTR1 through 5. We recently reported that intracerebroventricular
      (ICV) injection of somatostatin stimulates feeding behavior in chicks. However,
      the specific receptors which mediate this orexigenic effect have not been
      identified in chicks. Thus, the purpose of the present study was to identify the
      receptor subtypes involved in somatostatin-induced feeding using 5 somatostatin
      analogs. Chicks that received vapreotide and octreotide (less than 3nmol), which
      are agonist of SSTR2 and SSTR5, increased their food intake. Additionally, chicks
      ICV injected with BIM23056 or L-817,818 (SSTR3 and SSTR5 agonists, respectively)
      also had increased food intake. However, ICV injection of the SSTR4 agonist L
      803,087 did not cause an orexigenic effect, suggesting that SSTR4 might not be
      important in somatostatin-induced feeding behavior. In summary, results from this
      study may be interpreted as SSTR2, SSTR3 and SSTR5 are related to somatostatin
      associated feeding behavior in chicks.

PMID- 20826223
TI  - Effects of lysophosphatidic acid on the in vitro proliferation and
      differentiation of a novel porcine preadipocyte cell line.
AB  - We examined the effects of lysophosphatidic acid (LPA) on in vitro proliferation
      and differentiation of a porcine preadipocyte cell line, DFAT-P, and a mouse
      preadipocyte cell line, 3T3-L1. During the proliferation and differentiation
      phases, DFAT-P and 3T3-L1 cells expressed only the endothelial differentiation
      gene (EDG)-2 receptor and not EDG-4 and EDG-7 receptors. LPA promoted the
      proliferation of DFAT-P cells more extensively than that of 3T3-L1 cells. After
      adipogenic induction, LPA inhibited glycerol-3-phosphate dehydrogenase activity
      and lipid droplet accumulation, and suppressed peroxisome proliferator-activated
      receptor gamma (PPARgamma) protein expression, this inhibitory effect in DFAT-P
      cells was twice as high as that in 3T3-L1 cells. Furthermore, treatments with low
      LPA concentrations significantly inhibited adipocyte differentiation in DFAT-P
      cells but not in 3T3-L1 cells. We conclude that LPA promotes the proliferation of
      porcine preadipocytes through the EDG-2 receptor but inhibits their
      differentiation, and these effects depend on the down-regulation of PPARgamma
      expression via the EDG-2 receptor. Furthermore, DFAT-P cells are more sensitive
      to LPA than 3T3-L1 cells. These findings in a porcine model will contribute to
      the understanding of LPA action mechanisms on in vitro proliferation and
      differentiation of preadipocytes in domestic animals and/or humans.

PMID- 20826224
TI  - A functional analysis of N-glycosylation-related genes on sialylation of
      recombinant erythropoietin in six commonly used mammalian cell lines.
AB  - Significant efforts have been made to improve the sialylation of recombinant
      glycoproteins with the aim of extending their in vivo circulation time. Here, we
      report a systematic functional analysis of 31 N-glycosylation-related genes on
      sialylation of recombinant EPO in six cell lines. BHK and CHO cells were found to
      sialylate recombinant EPO most effectively. None of the 31 genes, individually or
      in combination, was able to improve EPO sialylation in these cells. HEK293, Cos-7
      and 3T3 cells showed intermediate sialylation capabilities, whereas NS0 cells
      sialylated recombinant EPO poorly. Overexpression of ST6GalI, ST3GalIII or
      ST3GalIV, but not ST3GalVI, was able to improve EPO sialylation in these four
      cell lines. qRT-PCR experiments revealed that ST3GalIII and ST3GalIV are indeed
      under expressed in HEK293, 3T3 and NS0 cells. Co-expression of upstream
      glycogenes failed to synergize with these sialyltransferases to further enhance
      sialylation, suggesting that the upstream glycogenes are all expressed at
      sufficient levels.

PMID- 20826225
TI  - Applications of nanoparticles in ophthalmology.
AB  - Nanocarriers, such as nanoparticles, have the capacity to deliver ocular drugs to
      specific target sites and hold promise to revolutionize the therapy of many eye
      diseases. Results to date strongly suggest that ocular medicine will benefit
      enormously from the use of this nanometric scale technology. One of the most
      important handicaps of the eye as a target organ for drugs is the presence of
      several barriers that impede direct and systemic drug access to the specific site
      of action. Superficial barriers include the ocular surface epithelium and the
      tear film, and internal barriers include the blood-aqueous and blood-retina
      barriers. Topical application is the preferred route for most drugs, even when
      the target tissues are at the back part of the eye where intraocular injections
      are currently the most common route of administration. Direct administration
      using any of these two routes faces many problems related to drug
      bioavailability, including side effects and repeated uncomfortable treatments to
      achieve therapeutic drug levels. In this regard, the advantages of using
      nanoparticles include improved topical passage of large, poorly water-soluble
      molecules such as glucocorticoid drugs or cyclosporine for immune-related, vision
      threatening diseases. Other large and unstable molecules, such as nucleic acids,
      delivered using nanoparticles offer promising results for gene transfer therapy
      in severe retinal diseases. Also, nanoparticle-mediated drug delivery increases
      the contact time of the administered drug with its target tissue, such as in the
      case of brimonidine, one of the standard treatments for glaucoma, or
      corticosteroids used to treat autoimmune uveitis, a severe intraocular
      inflammatory process. In addition, nanocarriers permit the non-steroidal anti
      inflammatory drug indomethacin to reach inner eye structures using the
      transmucosal route. Finally, nanoparticles allow the possibility of targeted
      delivery to reach specific types of cancer, such as melanoma, leaving normal
      cells untouched. This review summarizes experimental results from our group and
      others since the beginnings of nanocarrier technology to deliver drugs to
      different locations in the eye. Also, it explores the future possibilities of
      nanoparticles not only as drug delivery systems but also as aides for diagnostic
      purposes.

PMID- 20826227
TI  - Miniaturized flow cytometric in vitro micronucleus assay represents an efficient
      tool for comprehensively characterizing genotoxicity dose-response relationships.
AB  - This laboratory has developed a flow cytometric approach for scoring in vitro
      micronuclei (In Vitro MicroFlow((r))) whose characteristics are expected to
      benefit studies designed to comprehensively investigate genotoxicity dose
      response relationships. In particular, new experimental designs become possible
      when automated scoring is combined with treatment, processing and sampling that
      all occur in microtiter plates. To test this premise, experiments described
      herein investigated micronucleus (MN) formation in TK6 cells treated with
      genotoxic agents applied at 22 closely spaced concentrations in quadruplicate,
      with 10,000 cells analyzed per replicate. The genotoxicants colchicine,
      vinblastine sulfate, ethyl methanesulfonate, methyl methanesulfonate, ethyl
      nitrosourea, methyl nitrosourea, and bleomycin were applied continuously for 24
      30 h. Following treatment, all cell processing, sampling and data acquisition
      steps were accomplished in the same 96-well plate. Data acquisition occurred in a
      walk-away mode via the use of a high throughput sampling device. The resulting
      flow cytometric MN values were evaluated with a statistical model that indicated
      non-linear relationships describe the data better than linear fits. The one
      exception was bleomycin, where MN induction was consistently best described by a
      linear dose-response relationship. Collectively, these results suggest that flow
      cytometry represents a practical and efficient approach for thoroughly examining
      the dose-response relationship, and clearly benefits studies that seek to
      characterize no observable genotoxic effect levels, lowest observable genotoxic
      effect levels, and/or benchmark doses.

PMID- 20826228
TI  - Marine pharmacology in 2007-8: Marine compounds with antibacterial,
      anticoagulant, antifungal, anti-inflammatory, antimalarial, antiprotozoal,
      antituberculosis, and antiviral activities; affecting the immune and nervous
      system, and other miscellaneous mechanisms of action.
AB  - The peer-reviewed marine pharmacology literature in 2007-8 is covered in this
      review, which follows a similar format to the previous 1998-2006 reviews of this
      series. The preclinical pharmacology of structurally characterized marine
      compounds isolated from marine animals, algae, fungi and bacteria is discussed in
      a comprehensive manner. Antibacterial, anticoagulant, antifungal, antimalarial,
      antiprotozoal, antituberculosis and antiviral activities were reported for 74
      marine natural products. Additionally, 59 marine compounds were reported to
      affect the cardiovascular, immune and nervous systems as well as to possess anti
      inflammatory effects. Finally, 65 marine metabolites were shown to bind to a
      variety of receptors and miscellaneous molecular targets, and thus upon further
      completion of mechanism of action studies, will contribute to several
      pharmacological classes. Marine pharmacology research during 2007-8 remained a
      global enterprise, with researchers from 26 countries, and the United States,
      contributing to the preclinical pharmacology of 197 marine compounds which are
      part of the preclinical marine pharmaceuticals pipeline. Sustained preclinical
      research with marine natural products demonstrating novel pharmacological
      activities, will probably result in the expansion of the current marine
      pharmaceutical clinical pipeline, which currently consists of 13 marine natural
      products, analogs or derivatives targeting a limited number of disease
      categories.

PMID- 20826226
TI  - Retinal connectivity and primate vision.
AB  - The general principles of retinal organization are now well known. It may seem
      surprising that retinal organization in the primate, which has a complex visual
      behavioral repertoire, appears relatively simple. In this review, we primarily
      consider retinal structure and function in primate species. Photoreceptor
      distribution and connectivity are considered as are connectivity in the outer and
      inner retina. One key issue is the specificity of retinal connections; we suggest
      that the retina shows connectional specificity but this is seldom complete, and
      we consider here the functional consequences of imprecise wiring. Finally, we
      consider how retinal systems can be linked to psychophysical descriptions of
      different channels, chromatic and luminance, which are proposed to exist in the
      primate visual system.

PMID- 20826229
TI  - Pulmonary cytochrome P450 enzymes belonging to the CYP4B subfamily from an
      Australian marsupial, the tammar wallaby (Macropus eugenii).
AB  - Cytochromes P450 (CYPs) are critically important in the oxidative metabolism of a
      diverse array of xenobiotics and endogenous substrates. We have previously
      reported the cloning and characterisation of the koala CYP4A15, the first
      reported member of the CYP4 family from marsupials, and have demonstrated
      important species differences in CYP4A activity and tissue expression. In the
      present study, the cloning of CYP4B1 in the wallaby (Macropus eugenii) and their
      expression across marsupials is described. Rabbit anti-mouse CYP4B1 antibody
      detected immunoreactive proteins in lung and liver microsomes from all test
      marsupials, with relative weak signal detected from the koala, suggesting a
      species-specific expression. Microsomal 2-aminofluorene bio-activation (a CYP4B1
      marker) in wallaby lung was comparable to that of rabbit, with significant higher
      activities detected in wallaby liver and kidneys compared to rabbit. A 1548bp
      wallaby lung CYP4B complete cDNA, designated CYP4B1, which encodes a protein of
      510 amino acids and shares 72% nucleotide and 69% amino acid sequence identity to
      human CYP4B1, was cloned by polymerase chain reaction approaches. The results
      demonstrate the presence of wallaby CYP4B1 that shares several common features
      with other published CYP4Bs; however the wallaby CYP4B1 cDNA contains four extra
      amino acid residues at the NH2-terminal, a fundamentally conserved transmembrane
      anchor of all eukaryote CYPs.

PMID- 20826230
TI  - Tributyltin inhibits the oligomycin-sensitive Mg-ATPase activity in Mytilus
      galloprovincialis digestive gland mitochondria.
AB  - Tributyltin (TBT), widely employed in the past in antifouling paints, is one of
      the most toxic organic pollutants. Although recently banned, it still threatens
      coastal water ecosystems and accumulates in filter-feeding molluscs. TBT is known
      to act as a membrane-active toxicant; however data on mussels are scanty and
      exposure effects on mitochondrial ATPase activities remain hitherto unexplored.
      TBT effects on the mitochondrial Mg-ATPase activities in the digestive gland of
      Mytilus galloprovincialis were investigated both in vitro and in TBT-exposed
      mussels. Both an oligomycin-sensitive Mg-ATPase (OS Mg-ATPase) (70% of total Mg
      ATPase activity) and an oligomycin-insensitive ATPase (OI Mg-ATPase) (30%) were
      found. The OS-Mg-ATPase was as much as 70% in vitro inhibited by 0.7 MUM (203
      MUg/L) TBT, while higher concentrations promoted a partial inhibition release up
      to 5.0 MUM TBT; higher than 10.0 MUM TBT concentrations yielded nearly complete
      enzyme inhibition. Concentrations higher than 1 MUM TBT enhanced the OI Mg
      ATPase. Mussels exposed to 0.5 and 1.0 MUg/L TBT in aquaria showed a 30%
      depressed OS Mg-ATPase activity, irrespective of TBT dose and exposure time (24
      and 120 h). The OI Mg-ATPase activity was apparently refractory to TBT exposure
      and halved both in control and TBT-exposed mussels after 120 h exposure.

PMID- 20826231
TI  - Proteomic analysis of methyl parathion-responsive proteins in zebrafish (Danio
      rerio) brain.
AB  - Methyl parathion (MP), an organophosphorus pesticide used worldwide, has been
      associated with a wide spectrum of toxic effects on organisms in the environment.
      This study set out to analyze the alteration of protein profiles in MP-exposed
      zebrafish (Danio rerio) brain and find the proteins responsive to MP toxicity.
      Zebrafish were subjected to 1, 3 and 5mg/L MP and the proteomic changes in their
      brains were revealed using two-dimensional gel electrophoresis. Six protein spots
      were observed to be significantly changed by MP exposure. Among these, 4 spots
      were down-regulated, while 2 spots were up-regulated. These altered spots were
      excised from the gels and identified by matrix-assisted laser
      desorption/ionization time-of-flight tandem mass spectrometry and database
      searching. The results indicate that these proteins were involved in binding,
      catalysis, regulation of energy metabolism and cell structure. These data may
      provide novel biomarkers for the evaluation of MP contamination and useful
      insights for understanding the mechanisms of MP toxicity.

PMID- 20826232
TI  - Common rostrocaudal gradient of output from human intercostal motoneurones during
      voluntary and automatic breathing.
AB  - In voluntary breaths, driven through the motor cortex, the pattern of activation
      in human inspiratory intercostal muscles is unknown. We measured single motor
      unit behaviour in the first, third, and fifth parasternal intercostal muscles in
      5 subjects for 'quiet' and matched 'voluntary' inspirations. In voluntary
      breaths, the average onset, peak and end discharge rate of 264 inspiratory single
      motor units was greater in the first interspace compared to caudal spaces (p <
      0.05). Relative to the onset of inspiratory flow, the time of recruitment of
      single motor units and the onset of multiunit activity were also earlier in the
      first compared to the fifth interspace (p < 0.05). For 215 'common' motor units,
      peak discharge frequencies were ~20% higher in voluntary compared to quiet
      breaths (p < 0.05), due in part, to small differences in the pattern of
      breathing. A rostrocaudal gradient of motor unit activation across parasternal
      intercostal muscles was preserved in voluntary and involuntary tasks. A common
      mechanism may mediate this pattern of recruitment.

PMID- 20826233
TI  - Effects of strontium in modified biomaterials.
AB  - Strontium (Sr) plays a special role in bone remodelling, being associated with
      both the stimulation of bone formation and a reduction in bone resorption. Thus,
      the modification of biomaterials by partial or full substitution by Sr is
      expected to increase both bioactivity and biocompatibility. However, such effects
      have to be studied individually. Although no phase transition was found in Sr
      substituted hydroxyapatite (Sr-HA), Sr-containing calcium silicate (Sr-CS) or Sr
      containing borosilicate (Sr-BS), their biological performance was substantially
      affected by changes in the physico-chemical properties and Sr content of the
      materials. Three distinct outcomes were found for the presence of Sr: (1)
      increased HA solubility; (2) no significant effect on the degradation rate of CS;
      (3) apparent inhibition of the otherwise rapid degradation of BS. In each case
      the released Sr affected osteoblast proliferation and alkaline phosphatase
      activity, with clear evidence that an optimum Sr dose exists. Such chemical and
      biological variations must be disentangled for the behaviour to be properly
      understood and materials design to be advanced.

PMID- 20826234
TI  - The effect of hyaluronan injections into human knees on the number of bone and
      cartilage wear particles captured by bio-ferrography.
AB  - Osteoarthritis is characterized by degradation of cartilage and subchondral bone,
      releasing wear particles into the synovial fluid. Intra-articular injections of
      exogenous hyaluronan are often given to patients suffering from osteoarthritis in
      order to compensate for the reduction in the level of endogenous hyaluronan and
      to restore the rheological properties of the synovial fluid. The exact effect of
      these injections is still ambiguous. In this work bio-ferrography was used to
      capture magnetically labeled cartilage and bone debris from the synovial fluid in
      human knees before each of four injections (Euflexxa). The wear particles were
      counted and characterized microscopically and chemically. WOMAC, VAS, SF-36 and
      KS questionnaires indicated significant pain relief during the treatment, but
      suffered from inconsistency. Bio-ferrography showed a reduction in the
      concentration of both cartilage and bone particles, with a minimum after the
      third hyaluronan injection. The advantages of bio-ferrography as a primary
      assessment tool are discussed. The results indicate that while hyaluronan
      treatment may temporarily slow the wear rate to an extent beyond a placebo
      effect, it does not prevent joint degradation altogether.

PMID- 20826235
TI  - Duplication 4q associated with chronic cholestatic changes in liver biopsy.
AB  - We report a 15-day-old girl with partial trisomy 4q syndrome who presented with
      neonatal cholestasis. She had dysmorphic facial features and preaxial
      polysyndactyly of the right hand. The other findings were generalized
      hypertrichosis, pes equinovarus, oedema on feet and mild hepatomegaly. No
      specific reason for the cholestasis with elevated liver enzymes and direct
      bilirubinemia were characterized. Cytogenetic analyses revealed a karyotype
      46,XX,der(13)t(4;13)(q25;p13). This is the first patient with partial trisomy 4q
      syndrome presented with neonatal cholestasis.

PMID- 20826236
TI  - Acute lymphocytic leukaemia in a child with Beckwith-Wiedemann syndrome
      harbouring a CDKN1C mutation.
AB  - Beckwith-Wiedemann syndrome (BWS) is a rare overgrowth syndrome associated with
      an increased risk in childhood tumours. The phenotypic variability in BWS
      reflects its molecular heterogeneity. This syndrome is a multigenic disorder
      caused by dysregulation of imprinted growth regulatory genes in the 11p15.5
      region. The most commonly reported tumours in this syndrome are tumours of
      embryologic origin such as Wilms tumours, hepatoblastomas, neuroblastomas,
      rhabdomyosarcomas and adrenocortical carcinomas. We report the case of a 10-year
      old patient diagnosed with BWS, harbouring a CDKN1C (p57(KIP2)) mutation, who
      developed a T-type acute lymphoblastic leukaemia. To our knowledge it is the
      first report of an acute lymphoblastic leukaemia of T-type in a child with BWS.
      We discuss the possibility of a link between BWS and leukaemia via one of the few
      known negative regulator of hematopoiesis, the transforming growth factor beta
      pathway, depending upon the up-regulation of CDKN1C.

PMID- 20826237
TI  - E3 ubiquitin protein ligase, E6-associated protein (E6-AP) regulates PI3K-Akt
      signaling and prostate cell growth.
AB  - This study elucidates the role of E6-associated protein, E6-AP (a dual function
      steroid hormone receptor coactivator and ubiquitin-protein ligase) in the
      regulation of PI3K-Akt signaling pathway, prostate gland growth and
      proliferation. Here, we report the generation of transgenic mice and prostate
      cancer cell line, LNCaP cells that overexpress E6-AP protein. Using these models
      we show that the levels of total Akt and phosphorylated Akt (active Akt) are
      increased in E6-AP overexpressing prostate gland and LNCaP cells suggesting that
      E6-AP regulates the PI3K-Akt signaling pathway. The prostate glands in our
      transgenic mice are ~20% larger and produce preneoplastic lesions at the age of
      18 months. Our data also suggest that E6-AP modulates PI3K-Akt signaling pathway
      by both androgen-independent and -dependent mechanisms. In the androgen
      independent mechanism, E6-AP modulates PI3K-Akt signaling by regulating the
      protein levels of RhoA, a small GTPase, which is a negative regulator of the Akt
      signaling pathway. Further, we show that E6-AP, a known coactivator of AR,
      amplifies the androgen-dependent activation of PI3K-Akt signaling pathway. In
      addition, we show that stable overexpression of E6-AP in prostate cancer cells
      results in increased cell size and proliferation. Overall our data suggests that
      E6-AP regulates both the positive and negative modulators of the PI3K-Akt pathway
      in prostate cells which results in increased prostate cell growth, proliferation
      and decreased apoptosis.This article is part of a Special Issue entitled The 26S
      Proteasome: When degradation is just not enough!

PMID- 20826238
TI  - Triple antiplatelet therapy reduces ischemic events after drug-eluting stent
      implantation: Drug-Eluting stenting followed by Cilostazol treatment REduces
      Adverse Serious cardiac Events (DECREASE registry).

PMID- 20826240
TI  - Low-molecular-weight heparin versus unfractionated heparin in acute ST-segment
      elevation myocardial infarction patients undergoing primary percutaneous coronary
      intervention with drug-eluting stents.

PMID- 20826242
TI  - Reclassification of cardiovascular risk using integrated clinical and molecular
      biosignatures: Design of and rationale for the Measurement to Understand the
      Reclassification of Disease of Cabarrus and Kannapolis (MURDOCK) Horizon 1
      Cardiovascular Disease Study.
AB  - BACKGROUND: Clinical predictive models leave gaps in our ability to stratify
      cardiovascular risk. High-throughput molecular profiling promises to improve risk
      classification. METHODS: Horizon 1 of the Measurement to Understand the
      Reclassification of Disease of Cabarrus and Kannapolis (MURDOCK) Study was
      conceived to apply emerging molecular techniques to existing data sets to
      characterize mechanistic diversity underlying complex human diseases, response to
      therapy, and prognosis. No previous studies have applied multiple, complementary
      molecular techniques in combination with well-developed clinical risk models to
      refine cardiovascular risk prediction. The MURDOCK Cardiovascular Disease Study
      will assess molecular profiles integrated with clinical data in "clinomic"
      profiles for cardiovascular risk classification. CONCLUSION: Herein, we describe
      the design of and rationale for the MURDOCK Cardiovascular Disease Study.

PMID- 20826243
TI  - Rationale and design of a randomized, double-blind trial comparing the effects of
      a 3-month clopidogrel-aspirin regimen versus aspirin alone for the treatment of
      high-risk patients with acute nondisabling cerebrovascular event.
AB  - BACKGROUND: Acute nondisabling cerebrovascular events are common and often
      portend a disabling stroke. Aspirin is the only antiplatelet agent to have been
      studied in patients presenting acutely with a cerebrovascular event, but the
      effect is modest and is reduced by a small increased risk of intracerebral
      hemorrhage. Treatment with the combination of clopidogrel and aspirin might be
      beneficial when taken soon after a transient ischemic attack (TIA) or minor
      stroke. The CHANCE trial is a randomized, double-blind, multicenter, placebo
      controlled trial to test an aggressive antiplatelet regimen in acute minor stroke
      or TIA. DESIGN: The study will randomize 5,100 Chinese patients with acute TIA or
      minor stroke to receive a 3-month regimen of clopidogrel initiated with a loading
      dose of 300 mg followed by 75 mg/d, combined with aspirin 75 mg/d during the
      first 21 days, or a 3-month regimen of aspirin 75 mg/d alone. The primary
      efficacy end point is percentage of patients with any stroke (ischemic or
      hemorrhage) at 3 months. Study visits will be performed on the day of
      randomization, at day 21, and at day 90. SUMMARY: CHANCE will determine whether
      clopidogrel combined with aspirin can prevent more strokes after acute minor
      stroke or TIA compared with aspirin alone-with an acceptable risk profile.

PMID- 20826244
TI  - The efficacy and safety of clopidogrel in vascular surgery patients with
      immediate postoperative asymptomatic troponin T release for the prevention of
      late cardiac events: Rationale and design of the Dutch Echocardiographic Cardiac
      Risk Evaluation Applying Stress Echo-VII (DECREASE-VII) trial.
AB  - BACKGROUND: Major vascular surgery patients are at high risk for developing
      asymptomatic perioperative myocardial ischemia reflected by a postoperative
      troponin release without the presence of chest pain or electrocardiographic
      abnormalities. Long-term prognosis is severely compromised and characterized by
      an increased risk of long-term mortality and cardiovascular events. Current
      guidelines on perioperative care recommend single antiplatelet therapy with
      aspirin as prophylaxis for cardiovascular events. However, as perioperative
      surgical stress results in a prolonged hypercoagulable state, the postoperative
      addition of clopidogrel to aspirin within 7 days after perioperative asymptomatic
      cardiac ischemia could provide improved effective prevention for cardiovascular
      events. STUDY DESIGN: DECREASE-VII is a phase III, randomized, double-blind,
      placebo-controlled, multicenter clinical trial designed to evaluate the efficacy
      and safety of early postoperative dual antiplatelet therapy (aspirin and
      clopidogrel) for the prevention of cardiovascular events after major vascular
      surgery. Eligible patients undergoing a major vascular surgery (abdominal aorta
      or lower extremity vascular surgery) who developed perioperative asymptomatic
      troponin release are randomized 1:1 to clopidogrel or placebo (300-mg loading
      dose, followed by 75 mg daily) in addition to standard medical treatment with
      aspirin. The primary efficacy end point is the composite of cardiovascular death,
      stroke, or severe ischemia of the coronary or peripheral arterial circulation
      leading to an intervention. The evaluation of long-term safety includes bleeding
      defined by TIMI criteria. Recruitment began early 2010. The trial will continue
      until 750 patients are included and followed for at least 12 months. SUMMARY:
      DECREASE-VII is evaluating whether early postoperative dual antiplatelet therapy
      for patients developing asymptomatic cardiac ischemia after vascular surgery
      reduces cardiovascular events with a favorable safety profile.

PMID- 20826245
TI  - Diastolic dysfunction: improved understanding using emerging imaging techniques.
AB  - Diastolic heart failure is increasing in prevalence. Although the pathophysiology
      is incompletely understood and current therapeutic strategies are limited,
      identification of diastolic dysfunction is important. We review the role of
      contemporary techniques with echocardiography and cardiac magnetic resonance
      imaging (CMRI) in the assessment of diastolic dysfunction. Cardiac
      catheterization is the criterion standard for demonstrating impaired relaxation
      and filling by making direct measurements; however, echocardiography has replaced
      it as the most clinically used tool. By evaluating mitral inflow pulsed-wave
      Doppler with and without the Valsalva maneuver, isovolumetric relaxation time,
      pulmonary venous flow Doppler, color M-mode velocity propagation, tissue Doppler
      imaging, and speckle tracking, echocardiography is considered an accurate method
      for diagnosis and grading diastolic dysfunction. Evaluation of diastolic function
      can also be performed by CMRI. Mitral valve inflow velocities, early deceleration
      time, and pulmonary vein flow velocities are diastolic parameters that can be
      measured by phase-contrast CMRI. Cardiac magnetic resonance imaging steady-state
      gradient echo can evaluate functional dimensions for time-volume curves; and
      myocardial tagging can assess ventricular diastolic "untwisting," which may be
      important for improved pathophysiologic understanding. Studies have compared
      echocardiography and CMRI for diagnosing diastolic dysfunction in small patient
      groups with similar results. Cardiac magnetic resonance imaging can now provide
      clinically relevant data regarding the underlying cause of diastolic dysfunction
      and offers promise to gain mechanistic insights for therapeutic strategy
      development and clinical trial planning.

PMID- 20826246
TI  - Influence of transfer-in rates on quality of care and outcomes at receiving
      hospitals in patients with non-ST-segment elevation myocardial infarction.
AB  - BACKGROUND: Patients with non-ST-segment elevation myocardial infarction (NSTEMI)
      are frequently transferred to tertiary hospitals for angiography and/or
      revascularization from hospitals lacking such capabilities. Given that patients
      who undergo invasive cardiac procedures are younger and have fewer comorbidities
      compared with those managed medically, the relative proportion of transfer-in
      patients at tertiary hospitals may influence comparisons of quality and
      guidelines adherence. METHODS: We evaluated 142,092 NSTEMI patients treated at
      396 revascularization-capable sites in the CRUSADE National Quality Improvement
      Initiative from 2001 to 2006. Transfer-in patients were included if they arrived
      at the receiving hospital after their first presentation to a different hospital.
      Hospitals were categorized into tertiles based upon their transfer-in rates (low,
      intermediate, and high) and adherence to practice guidelines recommendations for
      NSTEMI. In-hospital clinical outcomes were compared across hospital tertiles.
      RESULTS: Acute and discharge composite guidelines adherence scores improved at
      hospitals with an increasing proportion of transfer-in patients, both for
      transferred as well as for directly admitted patients. These better adherence
      scores were inversely associated with overall mortality, with the lowest
      mortality observed in patients at hospitals with the highest transfer-in rates.
      However, once adjusted for baseline confounders, the mortality rates for patients
      in the hospitals in the highest transfer-in tertile did not differ significantly
      compared with the sites in the lowest transfer-in tertile (odds ratio 1.02, 95%
      CI 0.90-1.16). CONCLUSIONS: Our findings show that the proportion of NSTEMI
      patients transferred into revascularization-capable hospitals varies
      significantly. Hospitals with a higher proportion of transfer-in patients tend to
      provide higher overall quality of NSTE acute coronary syndrome care; they also
      have lower overall in-hospital mortality, which may, in part, be related to the
      lower-risk baseline characteristics of patients at these hospitals.

PMID- 20826247
TI  - Elevated admission glucose is associated with increased long-term mortality in
      myocardial infarction patients, irrespective of the initially applied reperfusion
      strategy.
AB  - BACKGROUND: It is uncertain if elevated admission plasma glucose (APG) remains an
      independent determinant of longer-term mortality in myocardial infarction (MI)
      patients with early restoration of coronary reperfusion by primary percutaneous
      coronary intervention. The objective of the study was to describe the relation
      between elevated APG and long-term mortality in MI patients undergoing invasive
      management. METHODS: We studied 1,185 consecutive MI patients treated in the
      Medical Center Alkmaar in the separate years 1996 and 1999 (preinvasive era) and
      2003 and 2006 (invasive era). In both eras, APG was derived according to a
      standard protocol. A multivariate Cox regression model was created to study the
      relation between APG, reperfusion era, and 5-year mortality. RESULTS: During a
      median follow-up of 63 months, 261 patients had died. Mortality was lower in the
      invasive (19%) than in the preinvasive era (28%). Increased APG was associated
      with increased mortality, irrespective of the initial reperfusion strategy,
      although the relation was more pronounced in the preinvasive era (P value for
      heterogeneity of effects < .001). Each millimole-per-liter APG increase
      corresponded to a 7% increased mortality (adjusted hazard ratio 1.07, 95% CI 1.04
      1.10). Patients with an APG >11 mmol/L had nearly 2-fold higher mortality (hazard
      ratio 1.9, 95% CI 1.3-2.7) than those with lower values. CONCLUSION: Elevated APG
      remains a determinant of long-term mortality in MI patients, irrespective of the
      advances that have been made in reperfusion therapy.

PMID- 20826248
TI  - Temporal trend of in-hospital major bleeding among patients with non ST-elevation
      acute coronary syndromes.
AB  - BACKGROUND: Although randomized controlled trials support the use of intensive
      medical and invasive therapies for non-ST segment elevation acute coronary
      syndromes (NSTE-ACS), major bleeding is a serious treatment complication. We
      sought to determine the temporal trend of in-hospital major bleeding among
      patients with NSTE-ACS, in relation to the evolving management pattern. METHODS:
      We identified 14 111 NSTE-ACS patients enrolled in 4 successive, prospective,
      multicenter registries (ACS I, 1999-2001; ACS II, 2002-2003; GRACE, 2004-2007;
      and CANRACE, 2008) in Canada between 1999 and 2008. We collected data on patient
      characteristics, use of cardiac medications and procedures on standardized case
      report forms. In all registries, major bleeding was defined a priori as life
      threatening or fatal bleeding, bleeding requiring transfusion of >=2 U of packed
      red cells, or resulting in an absolute decrease in hemoglobin of >30g/L. RESULTS:
      A total of 14 111 patients had a final diagnosis of NSTE-ACS and were included in
      this study (3294 in the ACS-I registry, 1956 in the ACS-II registry, 7543 in
      GRACE, and 1318 in CANRACE). Over time, there was a substantial increase in the
      use of dual anti-platelet (aspirin and thienopyridine) therapy (P for trend
      <.001), and in rates of in-hospital cardiac catheterization and percutaneous
      coronary intervention (both Ps for trend <.001). Overall, major bleeding was
      relatively infrequent (1.7%). There was no significant increase in the unadjusted
      rates of major bleeding over time (P for trend = .19). In multivariable analysis
      adjusting for GRACE risk score and intensive treatment, enrolment period was not
      an independent predictor of bleeding (P for trend = .98). There was no
      interaction between the enrolment period and the use of intensive medical and
      invasive management. CONCLUSION: Despite more widespread use of dual anti
      platelet therapies and invasive cardiac procedures in the management of NSTE-ACS,
      the rate of major bleeding remains relatively low and has not increased
      significantly over time. Our findings suggest that physicians selectively target
      treatment for their patients, and these evidence-based therapies can be safely
      administered to ACS patients in clinical practice.

PMID- 20826249
TI  - Results of a phase 1, randomized, double-blind, placebo-controlled trial of bone
      marrow mononuclear stem cell administration in patients following ST-elevation
      myocardial infarction.
AB  - BACKGROUND: Initial clinical trials from Europe have demonstrated that the
      administration of bone marrow-derived mononuclear cells (BMCs) may improve left
      ventricular (LV) function in patients following ST-elevation myocardial
      infarction (STEMI). However, results from trials performed in the United States
      have not yet been presented. METHODS: We developed a phase 1, randomized, placebo
      controlled, double-blind trial to investigate the effects of BMC administration
      in patients following STEMI on recovery of LV function using cardiac magnetic
      resonance imaging (cMRI). Forty patients with moderate to large anterior STEMIs
      were randomized to 100 million intracoronary BMCs versus placebo 3 to 10 days
      following successful primary angioplasty and stenting (percutaneous coronary
      intervention) of the left anterior descending coronary artery. RESULTS:
      Administration of BMC was safely performed in a high-risk cohort with minimal
      major adverse clinical event rates, and all patients remain alive to date. Left
      ventricular ejection fraction increased from 49.0% +/- 9.5% at baseline to 55.2%
      +/- 9.8% at 6 months by cMRI in the BMC group (P < .05), which was not different
      from the increase in the placebo group (48.6% +/- 8.5% to 57.0% +/- 13.4%, P <
      .05). Left ventricular end-diastolic volume decreased by 4 mL/m(2) in the BMC
      group at 6 months but increased significantly in the placebo group (17 mL/m(2), P
      < .01). CONCLUSIONS: This phase 1 study from the United States confirms the
      ongoing safety profile of BMC administration in patients following STEMI. The
      improvement in LV ejection fraction at 6 months by cMRI in the cell therapy group
      was not different than the placebo group. However, BMC administration had a
      favorable effect on LV remodeling at 6 months.

PMID- 20826251
TI  - A severity scoring system for risk assessment of patients with cardiogenic shock:
      a report from the SHOCK Trial and Registry.
AB  - BACKGROUND: Early revascularization (ERV) is beneficial in the management of
      cardiogenic shock (CS) complicating myocardial infarction. The severity of CS
      varies widely, and identification of independent risk factors for outcome is
      needed. The effect of ERV on mortality in different risk strata is also unknown.
      We created a severity scoring system for CS and used it to examine the potential
      benefit of ERV in different risk strata using data from the SHOCK Trial and
      Registry. METHODS: Data from 1,217 patients (294 from the randomized trial and
      923 from the registry) with CS due to pump failure were included in a Stage 1
      severity scoring system using clinical variables. A Stage 2 scoring system was
      developed using data from 872 patients who had invasive hemodynamic measurements.
      The outcome was in-hospital mortality at 30 days. RESULTS: In-hospital mortality
      at 30 days was 57%. Multivariable modeling identified 8 risk factors (Stage 1):
      age, shock on admission, clinical evidence of end-organ hypoperfusion, anoxic
      brain damage, systolic blood pressure, prior coronary artery bypass grafting,
      noninferior myocardial infarction, and creatinine > or = 1.9 mg/dL (c-statistic =
      0.74). Mortality ranged from 22% to 88% by score category. The ERV benefit was
      greatest in moderate- to high-risk patients (P = .02). The Stage 2 model based on
      patients with pulmonary artery catheterization included age, end-organ
      hypoperfusion, anoxic brain damage, stroke work, and left ventricular ejection
      fraction <28% (c-statistic = 0.76). In this cohort, the effect of ERV did not
      vary by risk stratum. CONCLUSIONS: Simple clinical predictors provide good
      discrimination of mortality risk in CS complicating myocardial infarction. Early
      revascularization is associated with improved survival across a broad range of
      risk strata.

PMID- 20826252
TI  - Quality of life among patients undergoing transcatheter aortic valve
      implantation.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been introduced to
      offer a new treatment option for patients who are not eligible for conventional
      aortic valve replacement. Especially in this subset of patients, the expected
      improvement of quality of life (QoL) after valve implantation will be critical
      for decision-making for TAVI. METHODS: We performed a prospective analysis of 99
      patients (41 male) aged 82 years (range 57-94 years) who underwent TAVI. For
      assessment of QoL, the Short Form 36 Health Survey Questionnaire was used
      preoperatively and 3 months after TAVI. RESULTS: Thirty-day mortality rate was
      10.1%. The Short Form 36 Health Survey Questionnaire scores for physical
      functioning (34.7 +/- 2.8 vs 48.5 +/- 3.4, P < .001), bodily pain (61.7 +/- 3.1
      vs 73.2 +/- 2.9, P < .01), general health (47.1 +/- 1.9 vs 54.1 +/- 2.3, P <
      .01), and vitality (37 +/- 2.8 vs 46.1 +/- 2.7, P < .01) increased significantly
      3 months after TAVI compared with preoperative scores. No significant changes
      were found for role-physical (21.7 +/- 4.1 vs 31.1 +/- 5.1, P < .08), social
      functioning (74.6 +/- 3.4 vs 74.6 +/- 3.1, P = 1), and mental health (63 +/- 2.9
      vs 67.4 +/- 2.2, P = .17) 3 months after TAVI. Only the score for role-emotional
      (69.3 +/- 5.6 vs 51.7 +/- 6, P = .02) decreased significantly 3 months after TAVI
      compared with the preoperative score. Corresponding to these results, the
      physical health summarized score (31.2 +/- 1.2 vs 38.6 +/- 1.6, P < .001) was
      significantly increased 3 months after TAVI compared with the preoperative score,
      whereas the mental health summarized score (48.5 +/- 1.8 vs 47.3 +/- 1.7, P = .5)
      showed no changes. CONCLUSION: In patients who are not eligible for conventional
      aortic valve replacement, TAVI leads to a considerable QoL improvement within 3
      months after valve implantation.

PMID- 20826250
TI  - beta-Blocker use following myocardial infarction: low prevalence of evidence
      based dosing.
AB  - BACKGROUND: Quality improvement programs have shown increased use of beta
      blockers post-myocardial infarction (MI), but there are no data on whether
      appropriate doses are administered. METHODS: In a prospective registry that
      enrolled consecutive patients with MI, we evaluated beta-blocker dosing at
      discharge after MI and 3 weeks later and assessed clinical predictors for
      treatment with very low doses. We studied 1,971 patients (70.8% male) with a mean
      age of 63.9 +/- 13.7 years, of whom 48.2% had an ST-elevation MI. RESULTS: beta
      Blocker utilization rates following MI were 93.2% at discharge: 20.1% received
      <25% of target dose, 36.5% received 25% of target dose, 26.4% received 26% to 50%
      of target dose, and 17.0% received >50% of target dose. Between discharge and 3
      weeks, 76.4% had no change in beta-blocker dose, with 11.9% and 11.6% having
      their dose reduced and increased, respectively. Absence of hypertension, acute
      percutaneous coronary intervention, older age, and no angiotensin-converting
      enzyme inhibitor therapy were consistent predictors of treatment with very low
      beta-blocker doses. CONCLUSIONS: Underdosing of beta-blockers is highly prevalent
      among patients post-MI. This represents an important opportunity in quality
      improvement for the care of patients who have suffered an MI.

PMID- 20826253
TI  - Effects of smoking intensity and cessation on inflammatory markers in a large
      cohort of active smokers.
AB  - BACKGROUND: Cigarette smoking has been associated with increases in C-reactive
      protein (CRP) and leukocyte counts (white blood cell [WBC]); however, the effects
      of smoking intensity and smoking cessation on inflammatory markers have not been
      evaluated prospectively in a large, modern cohort of current smokers. METHODS:
      White blood cell count and high-sensitivity CRP were measured in current smokers
      enrolled in a randomized, prospective clinical trial of 5 smoking cessation
      pharmacotherapies. Smoking intensity parameters included cigarettes per day, pack
      years, Fagerstrom Test of Nicotine Dependence score, and carbon monoxide levels.
      C-reactive protein also was measured after 1 year with assessment of abstinence
      status. RESULTS: The 1,504 current smokers (58% female) were (mean [SD]) 44.7
      (11.1) years old, smoked 21.4 (8.9) cigarettes per day, and had a smoking burden
      of 29.4 (20.4) pack-years. Log(CRP) was not associated with any marker of smoking
      intensity, except for a weak correlation with pack-years (r = 0.05, P = .047). In
      contrast, statistically significant correlations were observed between all 4
      markers of smoking intensity and WBC count (all P <= .011). In multivariable
      models, waist circumference (P < .001) and triglycerides (P < .05), but no
      markers of smoking intensity, were associated with log(CRP). However, pack-years
      (P = .002), cigarettes per day (P = .013), carbon monoxide (P < .001), and
      Fagerstrom Test of Nicotine Dependence (P < .001) were independently associated
      with WBC count. After 1 year, log(CRP) (P = .296) and changes in log(CRP) (P =
      .455) did not differ between abstainers and continuing smokers. CONCLUSIONS:
      Smoking intensity is associated with increased WBC count, but not CRP levels.
      Smoking cessation does not reduce CRP. The relationship between CRP and smoking
      intensity may be masked by CRP's stronger relationship with adiposity.

PMID- 20826254
TI  - Serum magnesium and risk of sudden cardiac death in the Atherosclerosis Risk in
      Communities (ARIC) Study.
AB  - BACKGROUND: We hypothesized that serum magnesium (Mg) is associated with
      increased risk of sudden cardiac death (SCD). METHODS: The Atherosclerosis Risk
      in Communities Study assessed risk factors and levels of serum Mg in a cohort of
      45- to 64-year-old subjects in 1987-1989 (n = 14,232). After an average of 12
      years of follow-up, we observed 264 cases of SCD, as determined by physician
      review of all suspected cases. We used proportional hazards regression to
      evaluate the association of serum Mg with risk of SCD. RESULTS: Individuals in
      the highest quartile of serum Mg were at significantly lower risk of SCD in all
      models. This association persisted after adjustment for potential confounding
      variables, with an almost 40% reduced risk of SCD (hazard ratio 0.62, 95% CI 0.42
      0.93) in quartile 4 versus 1 of serum Mg observed in the fully adjusted model.
      CONCLUSIONS: This study suggests that low levels of serum Mg may be an important
      predictor of SCD. Further research into the effectiveness of Mg supplementation
      for those considered to be at high risk for SCD is warranted.

PMID- 20826255
TI  - Prevalence and prognosis of left ventricular diastolic dysfunction in the
      elderly: The PROTEGER Study.
AB  - BACKGROUND: Left ventricular diastolic dysfunction (LVDD) was reported as a
      significant predictor of mortality, mainly in patients with heart failure.
      However, prospective data are scarce in the hospitalized elderly population.
      METHODS: We studied the association of severe LVDD, defined by conventional
      echocardiographic parameters, with cardiovascular and all-cause mortality in a
      population of 331 hospitalized elderly patients with a history of cardiovascular
      disease (mean age +/- SD, 87 +/- 7 years). After a mean follow-up of 378 days,
      110 deaths occurred. RESULTS: Compared with left ventricular systolic dysfunction
      (LVSD), subjects with severe diastolic dysfunction had a similar prevalence (12%
      vs 10%) and similar cardiovascular and all-cause mortality (18% vs 19%, 49% vs
      50%). Both cardiovascular and all-cause mortality increased progressively and
      significantly with increasing number of diagnostic criteria of LVDD (P = .035, P
      = .013) and reached 48.7% for all-cause mortality when at least 2 criteria were
      met. In addition to cardiovascular risk factors and LVSD, severe LVDD provided
      incremental and independent prognostic information of all-cause mortality with
      increased chi(2) value of Cox regression model (48.1 vs 43.5, P = .022).
      CONCLUSIONS: Severe LVDD, diagnosed by conventional echocardiography, has similar
      prevalence and prognosis as LVSD and provides incremental prognostic value, which
      highlights the clinical significance of routine evaluation of LVDD in risk
      assessment strategies of the hospitalized elderly.

PMID- 20826257
TI  - Protective effects of the angiotensin II receptor blocker telmisartan on
      epirubicin-induced inflammation, oxidative stress, and early ventricular
      impairment.
AB  - BACKGROUND: Oxidative stress and RAAS play an important role in the occurrence of
      anthracyclines-induced cardiotoxicity. Telmisartan, an angiotensin II type 1
      receptor blocker, inhibits activation of superoxide sources and induces anti
      inflammatory effects. METHODS: The possible role of telmisartan in preventing
      myocardial damage induced by epirubicin (EPI) was investigated. Forty-nine
      patients free from cardiovascular diseases affected by a variety of solid cancers
      were examined. Eligible patients were randomized to receive telmisartan (40 mg/d;
      TEL, n = 25) or placebo (PLA, n = 24) starting 1 week before chemotherapy.
      Patients were studied by means of echocardiography, tissue Doppler, and strain
      and strain rate (SR) imaging. We also measured plasma levels of inflammatory and
      oxidative stress markers. All parameters were assessed at baseline and 7 days
      after every new EPI dose of 100 mg/m(2). RESULTS: An impairment of the SR peak
      was observed at the EPI dose of 200 mg/m(2), with no significant differences
      between TEL and PLA (1.41 +/- 0.31 vs 1.59 +/- 0.36/s). At growing cumulative
      doses of EPI, SR normalized only in TEL, showing a significant difference in
      comparison to PLA at EPI doses of 300 mg/m(2) (1.69 +/- 0.42 vs 1.34 +/- 0.18/s,
      P < .001) and 400 mg/m(2) (1.74 +/- 0.27 vs 1.38 +/- 0.24/s, P < .001). Moreover,
      a significant increase in reactive oxygen species and interleukin-6 was found in
      PLA; but these remained unchanged in TEL. CONCLUSIONS: We confirmed that EPI
      induced cardiotoxicity is primarily related to the inactivation of the cardiac
      antioxidant defenses. In addition, we showed that telmisartan can reduce EPI
      induced radical species, antagonize the inflammation, and reverse the early
      myocardial impairment.

PMID- 20826256
TI  - Fibrinogen and left ventricular myocardial systolic function: The Multi-Ethnic
      Study of Atherosclerosis (MESA).
AB  - BACKGROUND: Increasing evidence suggests that elevated plasma fibrinogen is
      associated with incident heart failure. However, the underlying
      pathophysiological mechanisms have not been well elucidated. METHODS: We examined
      the relationship between plasma fibrinogen level and peak systolic midwall
      circumferential strain (Ecc) at the base, mid cavity, and apex of the left
      ventricle measured by magnetic resonance imaging myocardial tagging in 1096
      participants without clinical cardiovascular disease enrolled in the Multi-Ethnic
      Study of Atherosclerosis (MESA). RESULTS: After adjustment for demographics,
      established risk factors and body mass index, elevated fibrinogen was
      independently associated with reductions in absolute Ecc indicative of impaired
      systolic function in all regions (all P < or = .015). The relationships were
      consistently significant upon further adjustment for measures of atherosclerosis
      (all P < .024) and were modestly attenuated with regional heterogeneity after
      additional adjustment for other inflammatory biomarker and N-terminal pro-brain
      natriuretic peptide. In this fully-adjusted model, every 1-SD (74 mg/dL)
      increment in plasma fibrinogen was independently associated with a reduction in
      left ventricular absolute Ecc of 0.29% (95% CI 0.03%-0.59%, P = .048) at the
      base, 0.22% (95% CI 0.006%-0.43%, P = .044) at mid cavity, 0.20% (95% CI = 
      0.035% to 0.43%, P = .097) at the apex, and 0.24% (95% CI = 0.05%-0.43%, P =
      .015) overall. CONCLUSIONS: Among asymptomatic individuals without clinical
      cardiovascular disease, elevated fibrinogen is independently associated with
      impaired myocardial systolic function. These findings support roles of
      inflammation, procoagulation, and hyperviscosity underlying hyperfibrinogenemia
      in the pathogenesis of incipient myocardial dysfunction.

PMID- 20826258
TI  - Left ventricular dysfunction as a risk factor for cardiovascular and
      noncardiovascular hospitalizations in African Americans.
AB  - BACKGROUND: A substantial portion of the public health burden of heart failure is
      due to hospitalizations, many of which are for causes other than cardiovascular
      disease. We assessed whether left ventricular (LV) systolic dysfunction was
      associated with increased risk of both cardiovascular and noncardiovascular
      hospitalizations in a community sample of African Americans. METHODS: African
      American participants from the Jackson, MS, site of the Atherosclerosis Risk in
      Communities (ARIC) study who underwent echocardiography were followed for 12
      years. Hospitalization rates among individuals with and without LV systolic
      dysfunction were compared using negative binomial regression. RESULTS: Among
      2,416 participants with echocardiograms, LV systolic dysfunction was found in 61
      (2.5%). Participants with LV dysfunction experienced 366 hospitalizations, a rate
      of 1.27 per person-year, compared with 0.25 per person-year among individuals
      without LV dysfunction. The incidence rate ratio adjusted for demographics,
      comorbidities, and other risk factors was 3.11 (95% CI 2.22-4.35). The adjusted
      rate ratios were 4.76 (95% CI 2.90-7.20) for cardiovascular and 2.67 (95% CI 1.82
      3.90) for noncardiovascular diagnoses, with similar findings in the subset of
      individuals with asymptomatic LV dysfunction. The percentage attributable risks
      for hospitalizations were 87% and 74% for cardiovascular and noncardiovascular
      causes (79% and 63% after adjustment). CONCLUSIONS: African American individuals
      with LV dysfunction are at an increased risk of hospitalization due to a wide
      range of causes, with noncardiovascular hospitalizations accounting for nearly
      half the increased risk. To the extent that estimates of risk focus on
      cardiovascular morbidity, they may underestimate the true health burden of LV
      dysfunction.

PMID- 20826259
TI  - Renin-angiotensin system-related gene polymorphisms are associated with risk of
      atrial fibrillation.
AB  - BACKGROUND: Renin-angiotensin system (RAS) plays an important role in atrial
      fibrillation (AF). Recently, many publications have studied the associations
      between RAS-related gene polymorphisms and AF risk, with inconsistent results. To
      further evaluate these associations, we carried out a meta-analysis of all the
      published studies. METHODS: Electronic searches were used to identify published
      studies evaluating RAS-related gene polymorphisms and AF risk before April 2009.
      We extracted data sets and performed meta-analysis with standardized methods.
      RESULTS: A meta-analysis of 12 publications on association between angiotensin
      converting enzyme (ACE insertion/deletion) and AF risk was performed. The pooled
      relative risk (RR) of allele D versus I was 1.19 (95% CI, 1.07-1.32, P < .01),
      pooled RR of DD and DI versus II was 1.31(95% CI, 1.09-1.58, P < .01) and 1.06
      (95% CI, 0.97-1.16, P = .22) respectively. In subgroup analysis, a stronger
      association was found in hypertensive population, Western ethnic, lone AF, and
      patients aged > or = 65 years, with pooled RR of DD versus II was 1.74 (95% CI,
      1.39-2.18, P < .01), 1.27 (95% CI, 1.01-1.59, P = .04), 1.53 (95% CI, 1.31-1.78,
      P < .01) and 1.38 (95% CI, 1.10-1.73, P < .01), respectively. CONCLUSION: The
      results suggested an association between ACE insertion/deletion and AF risk. More
      large-scale studies are warranted to document the conclusive evidence of the
      effects of the RAS genes on AF risk.

PMID- 20826260
TI  - Protective effect of the CYP2C19 *17 polymorphism with increased activation of
      clopidogrel on cardiovascular events.
AB  - BACKGROUND: The prodrug clopidogrel requires activation by cytochrome P-450 (CYP)
      enzymes for its antiplatelet effect. The genes encoding enzymes for clopidogrel
      activation are polymorphic, leading to reduced or increased function, depending
      on the respective genotype. Reduced-function alleles have been associated with an
      increase in cardiovascular events. METHODS: We tested the association of the
      presence of the ABCB1 (C/T) T-allele, CYP2C19*2 (G/A) A-allele, or CYP2C19*17
      (C/T) T-allele with the primary end point of the need of clinically-driven target
      lesion revascularization (TLR) and the secondary end points of major adverse
      cardiovascular events (MACE; including death, myocardial infarction [MI], and
      TLR) at 1 year in a high-risk population of 928 patients with acute MI. RESULTS:
      Carriers of the CYP2C19*17 T-allele, with increased clopidogrel activation, had a
      37% relative reduction in the TLR incidence, the primary end point (14.0% vs
      22.3%, P = .002), and a 22% relative reduction of the secondary end point MACE
      (22.0% vs 28.1%, P = .04) compared with noncarriers, respectively. The
      association of the T-allele with TLR remained significant in the multivariate
      analysis (P = .001). The ABCB1 (C/T) and the CYP2C19*2 (G/A) polymorphisms were
      not associated with the incidence of TLR or MACE. CONCLUSIONS: Based on the
      genetic analysis in a high-risk population of acute MI patients with
      interventional treatment and continuous clopidogrel therapy, our study found a
      protective effect for carriers of an increased-function CYP2C19*17 T-allele with
      significantly lower rates of TLR and MACE. T-allele carriers with acute MI and
      increased clopidogrel activation had significantly reduced clinical event rates.

PMID- 20826261
TI  - The additive blood pressure lowering effects of exercise intensity on post
      exercise hypotension.
AB  - BACKGROUND: Evidence contends lower levels of physical exertion reduce blood
      pressure (BP) as effectively as more rigorous levels. We compared the effects of
      low (40% peak oxygen consumption, Vo(2)peak), moderate (60% Vo(2)peak), and
      vigorous (100% Vo(2)peak) exercise intensity on the BP response immediately
      following aerobic exercise. We also examined clinical correlates of the BP
      response. METHODS: Subjects were 45 men (mean +/- SEM, 43.9 +/- 1.4 years) with
      elevated awake ambulatory BP (ABP, 144.5 +/- 1.5/85.4 +/- 1.2 mm Hg). Men
      completed four randomly assigned experiments: non-exercise control and three
      exercise bouts at low, moderate, and vigorous intensity. All experiments began
      with a baseline period of seated rest. Subjects left the laboratory wearing an
      ABP monitor. RESULTS: Systolic ABP increased 2.8 +/- 1.6 mm Hg less after low,
      5.4 +/- 1.4 mm Hg less after moderate, and 11.7 +/- 1.5 mm Hg less after vigorous
      than control over 9 h (P < .001). Diastolic ABP decreased 1.5 +/- 1.2 mm Hg more
      after low, 2.0 +/- 1.0 mm Hg more after moderate, and 4.9 +/- 1.3 mm Hg more
      after vigorous versus control over 9 h (P < .010). Baseline correlates of the
      systolic ABP post-exercise response to vigorous were fasting glucose (r = 
      0.415), C-reactive protein (r = -0.362), renin (r = -0.348), fasting insulin (r =
      0.310), and fasting low density lipoprotein (r = -0.298) (R(2) = 0.400, P =
      .002). Baseline correlates of the diastolic ABP post-exercise response to
      vigorous were Vo(2)peak (r = -0.431), fasting low density lipoprotein (r = 
      0.431), renin (r = -0.411), fibrinogen (r = 0.369), and fasting glucose (r = 
      0.326) (R(2) = 0.429, P < .001). CONCLUSIONS: The antihypertensive effects of
      exercise intensity occurred in dose response fashion. Clinicians should weigh the
      benefits and risks of prescribing vigorous exercise intensity for those with
      hypertension on an individual basis.

PMID- 20826262
TI  - Predictors of 90-day readmission among patients with acute severe hypertension.
      The cross-sectional observational Studying the Treatment of Acute hyperTension
      (STAT) study.
AB  - BACKGROUND: Acute severe hypertension can be a life-threatening emergency. The
      objective of this study was to describe the frequency of rehospitalization for
      patients with acute severe hypertension and to identify clinical predictors of 90
      day rehospitalization. METHODS: In this observational cross-sectional study,
      consecutive patients were identified retrospectively (January 2007 to April 2008)
      through uniform data query of hospital pharmacy databases in 25 hospitals in the
      United States. Eligible patients were > or =18 years old, had systolic blood
      pressure >180 mm Hg and/or diastolic blood pressure >110 mm Hg, and had received
      intravenous antihypertensive therapy within 24 hours of presentation. Data were
      collected on patient demographics, medical history, laboratory findings,
      antihypertensive therapies, resource utilization, hospital-associated events,
      readmission within 90 days of hospital discharge, and death up to 6 months
      following the index hospitalization. RESULTS: The 90-day readmission rate was 35%
      (354/1,009) of patients discharged home alive and with known readmission status;
      41% (144/354) were readmitted more than once. Of these 354 patients, readmission
      was for acute severe hypertension in 29% (n = 101). Eighteen (1.9%) patients died
      between hospital discharge and 90 days. Factors associated with readmission for
      hypertension included previous hospitalization for acute severe hypertension,
      history of drug abuse, and presenting with seizures or shortness of breath.
      Patients with an admitting diagnosis of hypertension were 94% more likely to be
      readmitted. CONCLUSIONS: More than one third of patients discharged home after
      hospitalization for severe hypertension were rehospitalized at least once within
      90 days, more than one quarter for acute severe hypertension. Further studies are
      warranted to determine the impact of other variables on readmission rates and
      clinical outcomes in this population.

PMID- 20826263
TI  - Regional myocardial blood flow measured by stress multidetector computed
      tomography as a predictor of recovery of left ventricular function after coronary
      artery bypass grafting.
AB  - BACKGROUND: Multidetector-row computed tomography (MDCT) applications have
      expanded to evaluation of myocardial blood flow (MBF) and viability. We
      quantified regional MBF pre- and post-coronary artery bypass grafting (CABG)
      using adenosine stress and cardiac 64-MDCT, and investigated whether the results
      predict MBF and left ventricular (LV) function recovery after CABG. METHODS: We
      studied 321 regions in 19 CABG patients who underwent adenosine stress 64-row
      MDCT perfusion imaging and cine magnetic resonance imaging pre- and post-CABG.
      Myocardial blood flow was estimated from linear regression equation slopes using
      Patlak plot analyses and compared with LV function by measuring wall thickening
      (%WT) using cine magnetic resonance imaging. RESULTS: Overall mean MBFs were 1.39
      +/- 0.49 and 1.95 +/- 0.49 mL/(g min) pre- and post-CABG (P < .0001). Myocardial
      blood flow in revascularized areas increased significantly (pre-CABG 1.18 +/-
      0.45, post-CABG 1.99 +/- 0.66 mL/[g min], P < .001), whereas nonischemic areas
      showed no difference (1.79 +/- 0.70 and 1.97 +/- 0.46 mL/[g min], P = .14).
      Revascularized areas with preoperative MBF > or = 0.9 mL/(g min) showed
      significantly greater MBF improvement than those with preoperative MBF <0.9 mL/(g
      min) (P = .04). In patients with preoperative LV dysfunction (ejection fraction
      <40%), %WT in revascularized areas with pre-CABG MBF > or = 0.9 mL/(g min)
      improved significantly after CABG (pre-%WT 40.9 +/- 22.9, post-%WT 52.8 +/- 20.6,
      P = .03) versus those with pre-CABG MBF <0.9 mL/(g min) (pre-%WT 53.2 +/- 35.5,
      post-%WT 42.5 +/- 17.0, P = .40). CONCLUSIONS: Our results demonstrated more
      significantly increased MBF post-CABG than pre-CABG, particularly in
      revascularized areas. Regional MBF before CABG may predict MBF and LV function
      recovery, in the short term, after CABG.

PMID- 20826264
TI  - Real-world outcome of coronary bifurcation lesions in the drug-eluting stent era:
      results from the 4,314-patient Italian Society of Invasive Cardiology (SICI-GISE)
      Italian Multicenter Registry on Bifurcations (I-BIGIS).
AB  - BACKGROUND: Drug-eluting stents (DESs) introduction has somewhat renewed the
      issues of strategy and stenting technique for treatment of bifurcation lesions.
      In particular, concerns remain on extensive use of DESs, especially in the side
      branch, and on time of dual antiplatelet therapy (DAT) discontinuation,
      reflecting lack of pertinent long-term data. This study aimed to evaluate
      clinical safety and efficacy of different strategies for bifurcations treatment
      in a large observational real-world registry. METHODS: A multicenter,
      retrospective Italian study of consecutive patients undergoing bifurcation
      percutaneous coronary intervention between January 2002 and December 2006 was
      performed. The primary end point was the long-term rate of major adverse cardiac
      events (MACEs). The role of DAT length on outcome was also analyzed. RESULTS: A
      total of 4,314 patients (4,487 lesions) were enrolled at 22 independent centers.
      In-hospital procedural success rate was 98.7%. After median follow-up of 24
      months, MACEs occurred in 17.7%, with cardiac death in 3.4%, myocardial
      infarction in 4.0%, target lesion revascularization in 13.2%, and stent
      thrombosis in 2.9%. Extensive multivariable analysis showed that MACEs were
      independently predicted by age, diabetes, renal failure, systolic dysfunction,
      multivessel disease, myocardial infarction at admission, restenotic lesion, bare
      metal stent implantation, complex stenting strategy, and short duration of DAT.
      CONCLUSIONS: This large study based on current clinical practice in an unselected
      patient population presenting with bifurcation disease and submitted to
      percutaneous coronary intervention demonstrated favorable long-term clinical
      results in this challenging patient setting, especially when DESs, simple
      stenting strategy, and DAT for at least 6 months are used.

PMID- 20826265
TI  - Prognostic significance of high on-clopidogrel platelet reactivity after
      percutaneous coronary intervention: systematic review and meta-analysis.
AB  - BACKGROUND: A growing number of observational studies suggest that high on
      clopidogrel platelet reactivity (HPR) is associated with recurrent thrombotic
      events after percutaneous coronary intervention. We aimed to perform an updated
      systematic review and meta-analysis on the clinical relevance of HPR to summarize
      the available evidence and to define more precise effect estimates. METHODS:
      Relevant observational studies published between January 2003 and February 2010
      were searched that presented intent-to-treat analyses on the clinical relevance
      of HPR measured with an adenosine diphosphate (ADP)-specific platelet function
      assay. The main outcome measures were cardiovascular (CV) death,
      definite/probable stent thrombosis (ST), nonfatal myocardial infarction (MI), and
      a composite end point of reported ischemic events. The outcome parameters were
      pooled with the random-effect model via generic inverse variance weighting.
      RESULTS: Twenty studies comprising a total number of 9,187 patients qualified.
      High on-clopidogrel platelet reactivity appeared to be a strong predictor of MI,
      ST, and the composite end point of reported ischemic events (odds ratios [95%
      CI]: 3.00 [2.26-3.99], 4.14 [2.74-6.25], and 4.95 [3.34-7.34], respectively; P <
      .00001 for all cases). According to the meta-analysis, patients with HPR had a
      3.4-fold higher risk for CV death compared with patients with normal ADP
      reactivity (odds ratio 3.35, 95% CI 2.39-4.70, P < .00001). Although there were
      large differences in the methodology as well as in the definition of HPR between
      studies, the predicted risk for CV death, MI, or ST was not heterogeneous (I(2):
      0%, 0%, and 12%, respectively; P = not significant for all cases). CONCLUSIONS:
      High on-clopidogrel platelet reactivity, measured by an ADP-specific platelet
      function assay, is a strong predictor of CV death, MI, and ST in patients after
      percutaneous coronary intervention.

PMID- 20826266
TI  - Comparison of rotational with conventional coronary angiography.
AB  - BACKGROUND: Patient radiation exposure and consumption of contrast medium are
      considered major risks of diagnostic coronary angiography (CA). Rotation of the C
      arm during CA could provide similar diagnostic accuracy and lower radiation
      exposure and contrast medium consumption. METHODS: To compare feasibility,
      safety, diagnostic accuracy, patient radiation exposure, and consumption of
      contrast medium of rotational CA with the invasive standard technique,
      intraindividual comparisons of the results obtained by both techniques were
      performed in 235 patients with an indication for first-time elective CA. In
      addition to conventional angiography, we performed 2 isocentric radiographic
      coronary spins with cranial and caudal tilts by 20 degrees around the left
      coronary artery and 1 strict posteroanterior rotational spin around the right
      coronary artery. RESULTS: In 16 patients, rotational CA was not performed because
      of safety concerns. In a further 12 patients, image quality of rotational scans
      was considered inadequate. In the remaining 207 patients, both modes of CA were
      proven suitable for anonymized, separate analysis by 3 independent cardiologists.
      Intraindividual comparison of both CA modes revealed a high degree of diagnostic
      agreement (Cohen (K) >0.8 for all cardiologists and for each coronary segment).
      Contrast medium volume during rotational CA and conventional CA amounted to 31.9
      +/- 4.5 mL versus 52.2 +/- 8.0 mL (P < .001) and patient radiation exposure
      amounted to 5.0 +/- 2.6 Gy * cm(2) versus 11.5 +/- 5.5 Gy * cm(2) (P < .001),
      respectively. CONCLUSIONS: Rotational CA represents a safe and feasible method in
      clinical routine. Whereas diagnostic accuracy is similar to the usual
      conventional mode, consumption of contrast medium and patient radiation exposure
      are significantly reduced.

PMID- 20826267
TI  - Vulnerable disease may induce neointimal coverage after sirolimus-eluting stent
      implantation.
AB  - BACKGROUND: Neointimal formation can protect against thrombosis after sirolimus
      eluting stent (SES) implantation; however, promoters of neointimal formation are
      unknown. METHODS: Six-month follow-up angioscopy was performed in 141 consecutive
      patients with SES implantation. All patients received aspirin (100 mg) and
      ticlopidine (200 mg) daily until angioscopy. We defined 2 grades of neointimal
      coverage as follows: insufficient coverage including no or partial neointimal
      coverage of stent struts, and sufficient coverage. The possible promoters of
      neointimal formation that were evaluated in this study were the condition of
      coronary artery disease (stable angina or acute coronary syndrome); angioscopic
      markers, including visible thrombus and plaque color (white or yellow); serum
      markers, including low-density lipoprotein cholesterol, high-density lipoprotein
      cholesterol, fasting blood glucose, hemoglobin A(1c), high-sensitive C-reactive
      protein, and fibrinogen; blood pressure and smoking; intervention markers,
      including stent size and length and intravascular ultrasound measurements; and
      medication, including statins, anticoagulants, angiotensin-converting enzyme
      inhibitors/angiotensin II receptor blockers, calcium antagonists, and beta
      blockers. RESULTS: Univariate analysis revealed that high-sensitive C-reactive
      protein, plaque color, and the condition of coronary artery disease were
      significantly correlated with the grade of neointimal coverage. Multivariate
      analysis using these 3 parameters revealed that only acute coronary syndrome
      (vulnerable disease) significantly promoted neointimal coverage. CONCLUSION:
      Vulnerable disease may promote neointimal coverage after SES implantation.

PMID- 20826268
TI  - Dominant mutations in RP1L1 are responsible for occult macular dystrophy.
AB  - Occult macular dystrophy (OMD) is an inherited macular dystrophy characterized by
      progressive loss of macular function but normal ophthalmoscopic appearance.
      Typical OMD is characterized by a central cone dysfunction leading to a loss of
      vision despite normal ophthalmoscopic appearance, normal fluorescein angiography,
      and normal full-field electroretinogram (ERGs), but the amplitudes of the focal
      macular ERGs and multifocal ERGs are significantly reduced at the central retina.
      Linkage analysis of two OMD families was performed by the SNP High Throughput
      Linkage analysis system (SNP HiTLink), localizing the disease locus to chromosome
      8p22-p23. Among the 128 genes in the linkage region, 22 genes were expressed in
      the retina, and four candidate genes were selected. No mutations were found in
      the first three candidate genes, methionine sulfoxide reductase A (MSRA), GATA
      binding 4 (GATA4), and pericentriolar material 1 (PCM1). However, amino acid
      substitution of p.Arg45Trp in retinitis pigmentosa 1-like 1 (RP1L1) was found in
      three OMD families and p.Trp960Arg in a remaining OMD family. These two mutations
      were detected in all affected individuals but in none of the 876 controls.
      Immunohistochemistry of RP1L1 in the retina section of cynomolgus monkey revealed
      expression in the rod and cone photoreceptor, supporting a role of RP1L1 in the
      photoreceptors that, when disrupted by mutation, leads to OMD. Identification of
      RP1L1 mutations as causative for OMD has potentially broader implications for
      understanding the differential cone photoreceptor functions in the fovea and the
      peripheral retina.

PMID- 20826269
TI  - A locus on chromosome 1p36 is associated with thyrotropin and thyroid function as
      identified by genome-wide association study.
AB  - Thyroid hormones are key regulators of cellular growth, development, and
      metabolism, and thyroid disorders are a common cause of ill health in the
      community. Circulating concentrations of thyrotropin (TSH), thyroxine (T4) and
      triiodothyronine (T3) have a strong heritable component and are thought to be
      under polygenic control, but the genes responsible are mostly unknown. In order
      to identify genetic loci associated with these metabolic phenotypes, we performed
      a genome-wide association study of 2,120,505 SNPs in 2014 female twins from the
      TwinsUK study and found a significant association between rs10917469 on
      chromosome 1p36.13 and serum TSH (p = 3.2 * 10(-8)). The association of
      rs10917469 with serum TSH was replicated (p = 2.0 * 10(-4)) in an independent
      community-based sample of 1154 participants in the Busselton Health Study. This
      SNP is located near CAPZB, which might be a regulator of TSH secretion and thus
      of pituitary-thyroid axis function. Twenty-nine percent of white individuals
      carry the variant, and the difference in mean TSH concentrations between wild
      type individuals and those homozygous for the minor G allele was 0.5 mU/l, which
      is likely to be clinically relevant. We also provide evidence of suggestive
      association (p < 5.0 * 10(-6)) of other SNPs with serum TSH, free T4, and free T3
      concentrations, and these SNPs might be good targets for further studies. These
      results advance understanding of the genetic basis of pituitary-thyroid axis
      function and metabolic regulation.

PMID- 20826270
TI  - Protein tyrosine phosphatase PTPN14 is a regulator of lymphatic function and
      choanal development in humans.
AB  - The lymphatic vasculature is essential for the recirculation of extracellular
      fluid, fat absorption, and immune function and as a route of tumor metastasis.
      The dissection of molecular mechanisms underlying lymphangiogenesis has been
      accelerated by the identification of tissue-specific lymphatic endothelial
      markers and the study of congenital lymphedema syndromes. We report the results
      of genetic analyses of a kindred inheriting a unique autosomal-recessive
      lymphedema-choanal atresia syndrome. These studies establish linkage of the trait
      to chromosome 1q32-q41 and identify a loss-of-function mutation in PTPN14, which
      encodes a nonreceptor tyrosine phosphatase. The causal role of PTPN14 deficiency
      was confirmed by the generation of a murine Ptpn14 gene trap model that
      manifested lymphatic hyperplasia with lymphedema. Biochemical studies revealed a
      potential interaction between PTPN14 and the vascular endothelial growth factor
      receptor 3 (VEGFR3), a receptor tyrosine kinase essential for lymphangiogenesis.
      These results suggest a unique and conserved role for PTPN14 in the regulation of
      lymphatic development in mammals and a nonconserved role in choanal development
      in humans.

PMID- 20826280
TI  - Pediatrics milestones: a developmental approach to the competencies.

PMID- 20826281
TI  - Preclinical noninvasive markers of atherosclerosis in children and adolescents
      with type 1 diabetes are influenced by physical activity.
AB  - OBJECTIVES: To measure preclinical noninvasive markers of atherosclerosis in
      youth with type 1 diabetes (T1DM), and to determine their associations between
      physical activity level and cardiorespiratory fitness (maximal oxygen consumption
      [VO2max]). STUDY DESIGN: This was a cross-sectional study including 32 patients
      with T1DM and 42 healthy subjects aged 6 to 17 years. Main outcome measures
      included arterial flow-mediated dilation (FMD) and intima-media thickness with
      high-resolution ultrasonography; physical activity by accelerometer (valid 26
      patients with T1DM, 35 healthy subjects) and VO2max. RESULTS: Compared with
      healthy control subjects, patients with T1DM had higher intima-media thickness
      (mean 0.50 mm [0.48-0.52, 95% CI] vs 0.48 [0.47-0.49], P=.02) and reduced FMD
      (4.9% [4.1%-5.7%] vs 7.3 [6.4-8.1], P=.001), VO2max (45.5 mL/kg/min [43.0-48.0]
      vs 48.7 [46.7-50.6], P<or=.001), total (567.1 [458.6-675.6] vs 694.9 [606.6
      883.2] counts per minute, P=.001) and moderate-to-vigorous physical activity.
      Patients with T1DM who did more than 60 min/day(-1) of moderate-to-vigorous
      physical activity had similar FMD compared with relatively inactive healthy
      subjects, but not as high as active control subjects. CONCLUSION: Youth with T1DM
      present early signs of atherosclerosis, as well as low physical activity level
      and cardiorespiratory fitness. Endothelial function is enhanced in patients who
      practice more than 60 min/day(-1) of moderate-to-vigorous physical activity.

PMID- 20826285
TI  - Creation and initial evaluation of a Stool Form Scale for children.
AB  - OBJECTIVE: To develop a pediatric stool form rating scale and determine its
      interrater reliability, intrarater reliability, and agreement among pediatric
      gastroenterologists. STUDY DESIGN: An ordinal stool scale with 5 categorical
      stool form types was created on the basis of the Bristol Stool Form Scale, and 32
      color 2-dimensional stool photographs were shown to 14 pediatric
      gastroenterologists. Each gastroenterologist rated the stool form depicted in
      each photograph with the modified stool scale. Ten gastroenterologists agreed to
      rerate the stool form depicted in each photograph a minimum of 6 months after the
      first rating. RESULTS: A total of 448 ratings were completed; 430 (94%) of all
      ratings were within at least 1 category type of the most common (modal) rating
      for each photograph. Eight (25%) stool photographs had complete agreement among
      all raters. Interrater and intrarater reliability was high with a single measure
      intraclass correlation of 0.85 (95% confidence interval: 0.78-0.91; P<.001) and
      0.87 (95% confidence interval: 0.81-0.92; P<.001), respectively. CONCLUSION: A
      modified pediatric Bristol Stool Form Scale provided a high degree of interrater
      reliability, intrarater reliability, and agreement among pediatric
      gastroenterologists.

PMID- 20826287
TI  - Differentiating a mendosal suture from a skull fracture.

PMID- 20826288
TI  - Randomized trials and registries in vascular surgery. Introduction.

PMID- 20826289
TI  - Understanding objective performance goals for critical limb ischemia trials.
AB  - Critical limb ischemia (CLI), the most advanced form of peripheral arterial
      disease, is associated with a high rate of limb loss and substantial mortality.
      Revascularization remains the cornerstone of limb salvage in the CLI patient, and
      surgical bypass is the established standard. Endovascular therapies, such as
      angioplasty, atherectomy, and stenting offer a less-invasive option, but evidence
      of efficacy is lacking, and no devices are currently approved specifically for
      CLI. Design and execution of clinical trials in the CLI population are
      challenging, in part because of the lack of consensus on cohort definitions and
      relevant endpoints. Recently, the Society for Vascular Surgery undertook an
      initiative to define therapeutic benchmarks, objective performance goals (OPGs),
      for CLI. Using surgical bypass with autogenous vein as the standard for
      comparison, OPGs were developed for nine safety and efficacy measures that could
      be utilized in the premarket assessment of new devices in CLI. Data from three
      large randomized controlled trials of surgical bypass for CLI were analyzed. We
      defined a major adverse limb event (MALE) as a key endpoint for revascularization
      therapies in CLI--inclusive of amputation (transtibial or above) or any major
      vascular reintervention (thrombectomy, thrombolysis, or major surgical procedure
      [new bypass graft, jump/interposition graft revision]) in the index limb. Freedom
      from perioperative (30-day) death or any MALE (MALE + POD) was suggested as the
      primary efficacy endpoint for a single-arm trial design in CLI, with an observed
      rate of 76.9% for the surgical bypass controls at 1 year. Specific high-risk
      subgroups were also defined from the surgical dataset--based on clinical (age
      older than 80 years and tissue loss), arterial anatomy (infrapopliteal disease),
      and conduit quality (inadequate saphenous vein) characteristics. Risk-adjusted
      OPG were developed for these subgroups of interest. These OPGs define a new set
      of benchmarks for assessing the performance of revascularization therapies in
      CLI, and should facilitate clinical trial design and device development in this
      arena.

PMID- 20826290
TI  - How to interpret data from the superficial femoral artery stenting trials and
      registries.
AB  - Recent advances in endovascular technologies have made catheter-based
      interventions a preferred treatment strategy in patients with intermittent
      claudication or ischemic rest pain of the lower extremity. Although the current
      body of literature is inundated with clinical reports favoring countless
      endovascular devices and treatment techniques for femoropopliteal occlusive
      disease, analysis of available clinical reports regarding femoropopliteal lesions
      can be an overwhelming undertaking. In this report, we examine various challenges
      associated with data interpretation of clinical literature on endovascular
      treatment of femoropopliteal occlusive disease. Particular attention is focused
      on prospective randomized trials and clinical registries evaluating treatment
      efficacy of self-expanding nitinol stent implantation in femoropopliteal lesions.
      Prospective trials on the efficacy of drug-eluting stent placement and covered
      stent implantation of the superficial femoral artery are also discussed.
      Understanding current literature related to prospective randomized trials on
      femoropopliteal disease interventions is important to formulate an optimal
      treatment strategy based on appropriate patient selection and disease
      stratification so that successful treatment outcome can be achieved.

PMID- 20826291
TI  - Carotid artery stenting: clinical trials and registry data.
AB  - Despite the lack of Level I evidence, carotid artery stenting (CAS) has emerged
      as an alternative to carotid endarterectomy (CEA). Furthermore, CAS has been met
      with considerable enthusiasm due to its minimally invasive nature and potential
      application to high-risk patient populations. Several investigations including
      multicenter registries and randomized controlled trials have been established and
      are currently underway in an effort to evaluate the noninferiority and efficacy
      of CAS as compared to CEA. To date, no trial has definitively shown equivalence
      of CAS to CEA for the treatment of carotid stenosis and consensus recommendations
      for use of CAS remain very restricted. Nevertheless, the existing data have
      provided useful information with respect to differential outcomes in subgroups,
      including symptom status, age, gender, and high-risk patient populations. Until
      the noninferiority of CAS is clearly demonstrated in a randomized controlled
      setting, CEA remains the gold standard for treatment of carotid stenosis and use
      of CAS must be carefully considered on an individual patient basis.

PMID- 20826292
TI  - Randomized clinical trials regarding management of atherosclerotic renovascular
      disease.
AB  - Prospective randomized clinical trials that support operative correction of
      atherosclerotic renovascular disease or catheter-based intervention compared with
      optimal medical management are lacking. Despite various limitations in study
      design, each of the five randomized trials reported to date had demonstrated no
      apparent benefit for renal artery intervention compared with medical management.
      Three ongoing randomized trials promise to provide additional data and the
      results of these latter studies will likely dictate future reimbursement through
      the Centers for Medicare and Medicaid Services.

PMID- 20826293
TI  - Interpretation of the results of OVER in the context of EVAR trial, DREAM, and
      the EUROSTAR registry.
AB  - Several early studies have shown the benefit of endovascular aneurysm repair in
      reducing procedure-related mortality and morbidity of open aneurysm repair. Three
      prospective randomized trials have addressed the advantages and disadvantages of
      the two procedures. These studies had shown some conflicting findings in survival
      and complications. We reviewed the largest registry for endovascular abdominal
      aortic repair and the three randomized trials to evaluate the similarities and
      differences in their outcomes. Cross-comparison of operative, aneurysm-related
      and all-cause mortality is presented. Patient characteristics, device
      specifications, procedure morbidity and reintervention rate of each study are
      evaluated.

PMID- 20826294
TI  - A review of clinical trials and registries in descending thoracic aortic
      aneurysms.
AB  - Aortic disease is a significant pathology, as it represents the 12(th) leading
      cause of overall death. Aneurysms of the descending thoracic aorta pose a small
      but significant part of this pathology. Traditional open descending thoracic
      aortic aneurysm (TAA) repair continues to be performed despite relatively high
      morbidity and mortality rates. As endovascular therapy to treat vascular disease
      has evolved, a paradigm shift has occurred such that likely most isolated TAAs
      are now repaired with an endovascular approach. Multiple, prospective trials have
      been performed comparing open and endovascular TAA repair with three company
      sponsored trials documenting clinical equipoise. In these studies, endovascular
      thoracic aortic aneurysm repair (ETAR) was mostly compared with historic controls
      or open repair from centers of excellence. While the trials all indicate that 30
      day peri-operative morbidity and mortality is lower in the ETAR group, these
      trials were not designed to determine which patient is best served by an open
      versus an endovascular approach. In addition, long-term follow-up data is
      limited. Registry data of patients undergoing ETAR seems to mirror that of the
      aforementioned clinical trials and indicates acceptable morbidity and mortality
      profiles when compared to published open TAA repair results. Future prospective
      studies focused on patient selection likely will never be performed, as most
      believe the benefits of ETAR outweigh the lack of long term follow up data. This
      review will focus on repair of TAA, specifically clinical trial and registry data
      comparing open and endovascular repair.

PMID- 20826295
TI  - Treating blunt aortic injuries with endografts: pros and cons of a meta-analysis.
AB  - Modern management of blunt aortic injury (BAI) is based on evidence from mostly
      well-conducted meta-analyses as surrogates for prospective randomized controlled
      trials. There are several obvious pros and cons to this strategy. The advantages
      rest on the fact that it is unlikely that a prospective randomized trial
      comparing open surgical repair with endovascular repair will ever be conducted
      based on ethical grounds and the apparent survival advantage and reduced
      paraplegia rates associated with an endovascular approach; pooled data from high
      volume studies provides for higher statistical power; and a well-conducted meta
      analysis provides the ability to control for inter-study variation. The
      disadvantages of this approach are that meta-analyses are statistical
      examinations of scientific studies and not scientific studies in and of
      themselves; sources of bias cannot be controlled by the method of the analysis;
      and a heavy reliance on published studies can create exaggerated outcomes.
      Nonetheless, the studies reviewed in this article offer the best glimpse yet at
      the truth. The evidence grade to support endovascular over open repair for BAI is
      Level II (intermediate), which suggests that the described effect is plausible
      but is not quantified precisely or may be vulnerable to bias. The recommendation
      grade is B (provisional recommendation), which suggests that on balance of the
      evidence, endovascular repair for BAI is recommended with caution.

PMID- 20826296
TI  - What is the optimal duration of treatment for DVT? An update on evidence-based
      medicine of treatment for DVT.
AB  - Venous thromboembolism, including deep venous thrombosis (DVT) and pulmonary
      embolism, represent a major source of morbidity and mortality today. Incidence of
      DVT is estimated to be 56 to 160/100,000 population per year. Systemic
      anticoagulation with low molecular weight heparin or unfractionated heparin with
      initiation of oral vitamin K antagonist therapy has been shown to be beneficial
      in preventing pulmonary embolism and reducing extension and recurrence of DVT.
      The duration of anticoagulation following an episode of DVT is determined by the
      greatest predictors of recurrence. These include the presence of reversible risk
      factors, nonreversible risk factors, and no risk factors (idiopathic or
      unprovoked DVT). Short durations of anticoagulation are only appropriate for calf
      DVTs in patients with reversible risk factors. Patients with nonreversible risk
      factors, such as malignancy and certain inherited thrombophilias with a strong
      family history of venous thromboembolism will require lifelong anticoagulation.
      Those with proximal DVT due to reversible risk factors require 3 to 6 months of
      anticoagulation. Patients with idiopathic DVT require reassessment of risk-to
      benefit ratio of hemorrhage from oral vitamin K antagonist therapy compared to
      reducing risk of recurrence and frequently require prolonged oral anticoagulant
      therapy. Monitoring with d-dimer and serial ultrasounds may offer an
      individualized approach to therapy.

PMID- 20826297
TI  - Randomized trial evidence supporting a strategy of thrombus removal for acute
      DVT.
AB  - Reports of strategies of thrombus removal for acute deep venous thrombosis (DVT),
      especially in patients with iliofemoral DVT, consistently demonstrate improved
      outcomes relative to postthrombotic morbidity. Randomized trials support the
      observation that a strategy of thrombus removal reduces postthrombotic syndrome
      in patients with extensive proximal DVT. Unfortunately, there have been few
      randomized trials to date and they do not stand up to rigorous methodological
      review. This results in relatively weak recommendations by national and
      international guidelines for treatment strategies designed to eliminate thrombus.
      This report reviews the outcomes of randomized studies of treatments designed to
      remove thrombus from the venous system, including operative venous thrombectomy,
      systemic thrombolysis, and catheter-directed thrombolysis. Hopefully, the reader
      can put these results into perspective versus those anticipated with
      anticoagulation alone.

PMID- 20826299
TI  - Paint it black (or red, or green): optical and genetic tools illuminate
      inhibitory contributions to cortical circuit function.
AB  - Visual responses in the cortex are generated by the interactions of feedforward
      thalamic inputs with local inhibitory and excitatory circuitry, but the exact
      roles of different cell types in establishing response selectivity are unclear.
      Two papers in this issue of Neuron (Kerlin et al. and Runyan et al.) combine two
      photon imaging with guided electrical recordings to measure orientation tuning in
      molecularly defined groups of interneuron types.

PMID- 20826300
TI  - Neuroscience and education: an ideal partnership for producing evidence-based
      solutions to Guide 21(st) Century Learning.
AB  - Neuro-Education is a nascent discipline that seeks to blend the collective fields
      of neuroscience, psychology, cognitive science, and education to create a better
      understanding of how we learn and how this information can be used to create more
      effective teaching methods, curricula, and educational policy. Though still in
      its infancy as a research discipline, this initiative is already opening critical
      new dialog between teachers, administrators, parents, and brain scientists.

PMID- 20826301
TI  - Neuroscience and the future of early childhood policy: moving from why to what
      and how.
AB  - There is a need for greater synergy between advances in neuroscience and the
      formulation of innovative policies to improve life outcomes for children
      experiencing significant adversity. Translational developmental neuroscience can
      inform new theories of change to catalyze more effective interventions that lead
      to a more productive and healthier society.

PMID- 20826302
TI  - Children, wired: for better and for worse.
AB  - Children encounter technology constantly at home and in school. Television, DVDs,
      video games, the Internet, and smart phones all play a formative role in
      children's development. The term "technology" subsumes a large variety of
      somewhat independent items, and it is no surprise that current research indicates
      causes for both optimism and concern depending upon the content of the
      technology, the context in which the technology immerses the user, and the user's
      developmental stage. Furthermore, because the field is still in its infancy,
      results can be surprising: video games designed to be reasonably mindless result
      in widespread enhancements of various abilities, acting, we will argue, as
      exemplary learning tools. Counterintuitive outcomes like these, besides being
      practically relevant, challenge and eventually lead to refinement of theories
      concerning fundamental principles of brain plasticity and learning.

PMID- 20826303
TI  - The clinical-basic interface in defining pathogenesis in disorders of
      neurodevelopmental origin.
AB  - Human cognitive and social-emotional behaviors are heterogeneous, underscoring
      the challenges in modeling pathogenesis in disorders of neurodevelopmental origin
      in which these domains are dysfunctional. In general, animal models for these
      disorders are built to emulate our understanding of the clinical diagnosis, with
      mixed results. We suggest the utility of model systems lies in the use of
      different strategies to perturb hierarchical circuit development, to examine the
      behavioral dimensions that are most impacted, and to discern the capacity for,
      and heterogeneity of, neuroadaptation that will then inform treatment strategies.

PMID- 20826304
TI  - Brain mechanisms in early language acquisition.
AB  - The last decade has produced an explosion in neuroscience research examining
      young children's early processing of language. Noninvasive, safe functional brain
      measurements have now been proven feasible for use with children starting at
      birth. The phonetic level of language is especially accessible to experimental
      studies that document the innate state and the effect of learning on the brain.
      The neural signatures of learning at the phonetic level can be documented at a
      remarkably early point in development. Continuity in linguistic development from
      infants' earliest brain responses to phonetic stimuli is reflected in their
      language and prereading abilities in the second, third, and fifth year of life, a
      finding with theoretical and clinical impact. There is evidence that early
      mastery of the phonetic units of language requires learning in a social context.
      Neuroscience on early language learning is beginning to reveal the multiple brain
      systems that underlie the human language faculty.

PMID- 20826305
TI  - Structural MRI of pediatric brain development: what have we learned and where are
      we going?
AB  - Magnetic resonance imaging (MRI) allows unprecedented access to the anatomy and
      physiology of the developing brain without the use of ionizing radiation. Over
      the past two decades, thousands of brain MRI scans from healthy youth and those
      with neuropsychiatric illness have been acquired and analyzed with respect to
      diagnosis, sex, genetics, and/or psychological variables such as IQ. Initial
      reports comparing size differences of various brain components averaged across
      large age spans have given rise to longitudinal studies examining trajectories of
      development over time and evaluations of neural circuitry as opposed to
      structures in isolation. Although MRI is still not of routine diagnostic utility
      for evaluation of pediatric neuropsychiatric disorders, patterns of typical
      versus atypical development have emerged that may elucidate pathologic mechanisms
      and suggest targets for intervention. In this review we summarize general
      contributions of structural MRI to our understanding of neurodevelopment in
      health and illness.

PMID- 20826306
TI  - The development of human functional brain networks.
AB  - Recent advances in MRI technology have enabled precise measurements of correlated
      activity throughout the brain, leading to the first comprehensive descriptions of
      functional brain networks in humans. This article reviews the growing literature
      on the development of functional networks, from infancy through adolescence, as
      measured by resting-state functional connectivity MRI. We note several
      limitations of traditional approaches to describing brain networks and describe a
      powerful framework for analyzing networks, called graph theory. We argue that
      characterization of the development of brain systems (e.g., the default mode
      network) should be comprehensive, considering not only relationships within a
      given system, but also how these relationships are situated within wider network
      contexts. We note that, despite substantial reorganization of functional
      connectivity, several large-scale network properties appear to be preserved
      across development, suggesting that functional brain networks, even in children,
      are organized in manners similar to other complex systems.

PMID- 20826307
TI  - Adolescence: what do transmission, transition, and translation have to do with
      it?
AB  - Negotiating the transition from dependence on parents to relative independence is
      not a unique demand for today's youth but has a long evolutionary history
      (transmission) and is shared across mammalian species (translation). However,
      behavioral changes observed during this period are often described as delinquent.
      This review examines changes in explorative and emotive behaviors during the
      transition into and out of adolescence and the underlying neurobiological bases
      in the context of adaptive and maladaptive functions.

PMID- 20826308
TI  - Drosophila dscam proteins regulate postsynaptic specificity at multiple-contact
      synapses.
AB  - In both vertebrate and invertebrate visual systems, neurons form multiple-contact
      synapses at which a single presynaptic site releases neurotransmitter upon a
      discrete combination of different postsynaptic cells. Recognition mechanisms
      underlying the assembly of such synapses are not known. In Drosophila,
      photoreceptor terminals form tetrad synapses that incorporate an invariable pair
      of postsynaptic elements, one each from lamina interneuron L1 and L2, and two
      elements from other cells. Here, we demonstrate that Drosophila Dscam1 and
      Dscam2, genes encoding homophilic repulsive proteins, act redundantly to ensure
      the invariable combination of L1 and L2 postsynaptic elements at all tetrads. We
      demonstrate that this strict pairing is lost in Dscam1;Dscam2 double mutants.
      Thus, removing these two repulsive proteins allows elements from the same cell to
      incorporate into the same postsynaptic tetrad, altering the specificity of
      photoreceptor transmission. We propose that Dscams regulate synaptic specificity
      by excluding inappropriate partners at multiple-contact synapses.

PMID- 20826309
TI  - Modulation of gamma-secretase reduces beta-amyloid deposition in a transgenic
      mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized pathologically by the abundance of
      senile plaques and neurofibrillary tangles in the brain. We synthesized over 1200
      novel gamma-secretase modulator (GSM) compounds that reduced Abeta(42) levels
      without inhibiting epsilon-site cleavage of APP and Notch, the generation of the
      APP and Notch intracellular domains, respectively. These compounds also reduced
      Abeta(40) levels while concomitantly elevating levels of Abeta(38) and Abeta(37).
      Immobilization of a potent GSM onto an agarose matrix quantitatively recovered
      Pen-2 and to a lesser degree PS-1 NTFs from cellular extracts. Moreover, oral
      administration (once daily) of another potent GSM to Tg 2576 transgenic AD mice
      displayed dose-responsive lowering of plasma and brain Abeta(42); chronic daily
      administration led to significant reductions in both diffuse and neuritic
      plaques. These effects were observed in the absence of Notch-related changes
      (e.g., intestinal proliferation of goblet cells), which are commonly associated
      with repeated exposure to functional gamma-secretase inhibitors (GSIs).

PMID- 20826310
TI  - Global control of motor neuron topography mediated by the repressive actions of a
      single hox gene.
AB  - In the developing spinal cord, regional and combinatorial activities of Hox
      transcription factors are critical in controlling motor neuron fates along the
      rostrocaudal axis, exemplified by the precise pattern of limb innervation by more
      than fifty Hox-dependent motor pools. The mechanisms by which motor neuron
      diversity is constrained to limb levels are, however, not well understood. We
      show that a single Hox gene, Hoxc9, has an essential role in organizing the motor
      system through global repressive activities. Hoxc9 is required for the generation
      of thoracic motor columns, and in its absence, neurons acquire the fates of limb
      innervating populations. Unexpectedly, multiple Hox genes are derepressed in
      Hoxc9 mutants, leading to motor pool disorganization and alterations in the
      connections by thoracic and forelimb-level subtypes. Genome-wide analysis of
      Hoxc9 binding suggests that this mode of repression is mediated by direct
      interactions with Hox regulatory elements, independent of chromatin marks
      typically associated with repressed Hox genes.

PMID- 20826311
TI  - CDK5 serves as a major control point in neurotransmitter release.
AB  - CDK5 is an important kinase in nervous system function, controlling neural
      development and postsynaptic signal integration. Here we show that CDK5 plays a
      major role in controlling neurotransmitter release. Inhibition of CDK5 activity,
      by either acute or genetic means, leads to profound potentiation of presynaptic
      function, including unmasking of previously "silent" synapses. Removal of CDK5
      activity additionally unlocks access to the resting synaptic vesicle pool, which
      normally remains recalcitrant to exocytosis and recycling even following
      prolonged action potential stimuli. Presynaptic CDK5 levels are additionally
      severely depleted by chronic neuronal silencing, a treatment that is functionally
      similar to CDK5 knockdown with regard to presynaptic potentiation. Thus CDK5
      appears to be an integral element in presynaptic homeostatic scaling, and the
      resting vesicle pool appears to provide a potent functional presynaptic
      homeostatic control parameter. These studies thus pinpoint CDK5 as a major
      control point for modulation of neurotransmitter release in mammalian neurons.

PMID- 20826312
TI  - Gilgamesh is required for rutabaga-independent olfactory learning in Drosophila.
AB  - Cyclic AMP signaling in Drosophila mushroom body neurons, anchored by the
      adenylyl cyclase encoded by the rutabaga gene, is indispensable for olfactory
      memory formation. From a screen for new memory mutants, we identified alleles of
      the gilgamesh (gish) gene, which encodes a casein kinase Igamma homolog that is
      preferentially expressed in the mushroom body neurons. The gish-encoded kinase
      participates in the physiology of these neurons underlying memory formation since
      the mutant memory deficit was rescued with expression of a gish cDNA in these
      neurons only during adulthood. A cellular memory trace, detected as increased
      calcium influx into the alpha'/beta' neuron processes in response to the odor
      used for conditioning, was disrupted in gish mutants. Epistasis experiments
      indicated a lack of genetic interactions between gish and rutabaga. Therefore,
      gish participates in a rutabaga-independent pathway for memory formation and
      accounts for some of the residual learning that occurs in rutabaga mutants.

PMID- 20826313
TI  - Elevated BDNF after cocaine withdrawal facilitates LTP in medial prefrontal
      cortex by suppressing GABA inhibition.
AB  - Medial prefrontal cortex (mPFC) is known to be involved in relapse after cocaine
      withdrawal, but the underlying cellular mechanism remains largely unknown. Here,
      we report that after terminating repeated cocaine exposure in rats, a gradual
      increase in the expression of brain-derived neurotrophic factor (BDNF) in the
      mPFC facilitates activity-induced long-term potentiation (LTP) of excitatory
      synapses on layer V pyramidal neurons. This enhanced synaptic plasticity could be
      attributed to BDNF-induced suppression of GABAergic inhibition in the mPFC by
      reducing the surface expression of GABA(A) receptors. The BDNF effect was
      mediated by BDNF-TrkB-phosphatase 2A signaling pathway. Downregulating TrkB
      expression bilaterally in the mPFC reduced the locomotor hypersensitivity to
      cocaine 8 days after cocaine withdrawal. Thus, elevated BDNF expression after
      cocaine withdrawal sensitizes the excitatory synapses in the mPFC to undergo
      activity-induced persistent potentiation that may contribute to cue-induced drug
      craving and drug-seeking behavior.

PMID- 20826314
TI  - Neuronal activity drives localized blood-brain-barrier transport of serum insulin
      like growth factor-I into the CNS.
AB  - Upon entry into the central nervous system (CNS), serum insulin-like growth
      factor-1 (IGF-I) modulates neuronal growth, survival, and excitability. Yet
      mechanisms that trigger IGF-I entry across the blood-brain barrier remain
      unclear. We show that neuronal activity elicited by electrical, sensory, or
      behavioral stimulation increases IGF-I input in activated regions. Entrance of
      serum IGF-I is triggered by diffusible messengers (i.e., ATP, arachidonic acid
      derivatives) released during neurovascular coupling. These messengers stimulate
      matrix metalloproteinase-9, leading to cleavage of the IGF binding protein-3
      (IGFBP-3). Cleavage of IGFBP-3 allows the passage of serum IGF-I into the CNS
      through an interaction with the endothelial transporter lipoprotein related
      receptor 1. Activity-dependent entrance of serum IGF-I into the CNS may help to
      explain disparate observations such as proneurogenic effects of epilepsy,
      rehabilitatory effects of neural stimulation, and modulatory effects of blood
      flow on brain activity.

PMID- 20826315
TI  - Response features of parvalbumin-expressing interneurons suggest precise roles
      for subtypes of inhibition in visual cortex.
AB  - Inhibitory interneurons in the cerebral cortex include a vast array of subtypes,
      varying in their molecular signatures, electrophysiological properties, and
      connectivity patterns. This diversity suggests that individual inhibitory classes
      have unique roles in cortical circuits; however, their characterization to date
      has been limited to broad classifications including many subtypes. We used the
      Cre/LoxP system, specifically labeling parvalbumin(PV)-expressing interneurons in
      visual cortex of PV-Cre mice with red fluorescent protein (RFP), followed by
      targeted loose-patch recordings and two-photon imaging of calcium responses in
      vivo to characterize the visual receptive field properties of these cells.
      Despite their relative molecular and morphological homogeneity, we find that PV+
      neurons have a diversity of feature-specific visual responses that include sharp
      orientation and direction-selectivity, small receptive fields, and band-pass
      spatial frequency tuning. These results suggest that subsets of parvalbumin
      interneurons are components of specific cortical networks and that perisomatic
      inhibition contributes to the generation of precise response properties.

PMID- 20826317
TI  - Olfactory coding with patterns of response latencies.
AB  - The encoding of odors by spatiotemporal patterns of mitral/tufted (M/T) cells in
      the vertebrate olfactory bulb has been discussed controversially. Motivated by
      temporal constraints from behavioral studies, we investigated the information
      contained in odor-evoked first-spike latencies. Using simultaneous recordings of
      dozens of M/T cells with a high temporal resolution and quantitative ensemble
      correlation techniques, we show that latency patterns, and in particular latency
      rank patterns, are highly odor specific and reproducible. They reliably predict
      the odor identity as well as the odor concentration on a single-trial basis and
      on short timescales-in fact, more reliably than patterns of firing rates.
      Furthermore, we show that latency ranks exhibit a better reproducibility at the
      level of M/T cells than in olfactory receptor neurons. Our results suggest that
      the latency patterns of M/T cells contain all the information higher brain
      centers need to identify odors and their concentrations.

PMID- 20826316
TI  - Broadly tuned response properties of diverse inhibitory neuron subtypes in mouse
      visual cortex.
AB  - Different subtypes of GABAergic neurons in sensory cortex exhibit diverse
      morphology, histochemical markers, and patterns of connectivity. These subtypes
      likely play distinct roles in cortical function, but their in vivo response
      properties remain unclear. We used in vivo calcium imaging, combined with
      immunohistochemical and genetic labels, to record visual responses in excitatory
      neurons and up to three distinct subtypes of GABAergic neurons (immunoreactive
      for parvalbumin, somatostatin, or vasoactive intestinal peptide) in layer 2/3 of
      mouse visual cortex. Excitatory neurons had sharp response selectivity for
      stimulus orientation and spatial frequency, while all GABAergic subtypes had
      broader selectivity. Further, bias in the responses of GABAergic neurons toward
      particular orientations or spatial frequencies tended to reflect net biases of
      the surrounding neurons. These results suggest that the sensory responses of
      layer 2/3 GABAergic neurons reflect the pooled activity of the surrounding
      population--a principle that may generalize across species and sensory
      modalities.

PMID- 20826319
TI  - [Vancomycin, what else?].
AB  - Vancomycin and teicoplanin are glycopeptidic antibiotics that are used for many
      years in infections due to methicillin-resistant Staphylococcus aureus (MRSA).
      Nephrotoxicity of vancomycin and a slow clinical efficacy lead to discuss
      alternatives. Glycopeptides are less active than oxacillin against staphylococci
      susceptible to methicillin and should be reserved for infections due to MRSA.
      MRSA prevalence has decreased for several years in pediatrics but may remain
      frequent in neonatal intensive care units. Coagulase-negative staphylococci are a
      major cause of infections in neonates and are often resistant to methicillin.
      Community-acquired MRSA that produce Panton-Valentine leucocidin and are
      responsible for severe cutaneous infections and for rare severe necrotizing
      pneumonia in children spread over several years but their frequency remains low
      in France (2-4 % of MRSA). A new community-acquired MRSA clone, producer of toxic
      shock staphylococcal toxin is increasingly isolated. Efficacy of vancomycin
      against staphylococci is inversely correlated with MIC. MIC should be determined
      in severe infections and a seric concentration of vancomycin of 8 times the MIC
      should be reached as a target value. Glycopeptide resistance is rare in
      Staphylococcus aureus, but not that to teicoplanin in coagulase-negative
      staphylococci. MRSA remain currently susceptible to several antibiotics in
      addition to glycopeptides. Linezolid and daptomycin, recently introduced in
      therapy, have no indication in children but may have an interest.

PMID- 20826318
TI  - Differences in gamma frequencies across visual cortex restrict their possible use
      in computation.
AB  - Neuronal oscillations in the gamma band (30-80 Hz) have been suggested to play a
      central role in feature binding or establishing channels for neural
      communication. For these functions, the gamma rhythm frequency must be consistent
      across neural assemblies encoding the features of a stimulus. Here we test the
      dependence of gamma frequency on stimulus contrast in V1 cortex of awake behaving
      macaques and show that gamma frequency increases monotonically with contrast.
      Changes in stimulus contrast over time leads to a reliable gamma frequency
      modulation on a fast timescale. Further, large stimuli whose contrast varies
      across space generate gamma rhythms at significantly different frequencies in
      simultaneously recorded neuronal assemblies separated by as little as 400 microm,
      making the gamma rhythm a poor candidate for binding or communication, at least
      in V1. Instead, our results suggest that the gamma rhythm arises from local
      interactions between excitation and inhibition.

PMID- 20826320
TI  - [Levofloxacin in children].
AB  - Levofloxacin (levogyre form of ofloxacin) has been approved for the treatment of
      acute and chronic sinusitis, pneumonia, and exacerbation of bronchopulmonary
      diseases, urinary, digestive and biliary infections in adults. Its
      pharmacokinetic properties and microbiological spectrum, including penicillin non
      susceptible Streptococcus pneumoniae, methicillin-resistant Staphylococcus
      aureus, and Mycoplasma pneumoniae, suggest a potential interest in drug-resistant
      acute otitis media and community-acquired pneumonia. Only few studies have been
      performed in the paediatric population but they provided encouraging efficacy and
      safety data. Complementary data are needed before considering its use in Europe
      in the setting of a paediatric investigation plan.

PMID- 20826321
TI  - [Linezolide in paediatrics].
AB  - The spread of multiresistant Gram positive bacteria required the development of
      new drugs. Linezolid, a new oxazolidinone, is active against these pathogens and
      is marketed for the treatment of severe glycopeptides-resistant Gram positive
      bacteria in adults. Moreover, the availability of intravenous and oral
      formulation with an excellent bioavailability of the latter, is hoped to
      facilitate the management of these infections. Most information regarding the
      pharmacoketic profile, efficacy and tolerability of linezolid in pediatric
      derived from adults studies. In this review we summarize evidence regarding the
      uses of linezolid in children focusing on the clinical efficacy data and safety
      in serious Gram-positive infections and also in compassional uses.

PMID- 20826322
TI  - [Extended-spectrum beta-lactamase producing-enterobacteriaceae].
AB  - Extended-spectrum beta-lactamase (ESBLs) are defined as beta-lactamase capable of
      hydrolyzine oximino-cephalosporins and aztreonam and are encoded by mobile genes.
      The most frequently encountered ESBLs belong to the CTX-M, SHV, and TEM families.
      ESBLs were found first in Klebsiella pneumonia and then predominantly in E. coli.
      The incidence of patients with ESBLs E. coli increase since 2000 in Robert Debre
      Hospital. They were responsible of cystitis or pyelopnephritis and rarely of
      materno-foetal infections or neonatal meningitis. These strains were susceptible
      to colimycin, carbapenems and fosfomycin.

PMID- 20826323
TI  - [Description and investigation of an outbreak of extended-spectrum beta-lactamase
      producing Escherichia coli strain in a neonatal unit].
AB  - An outbreak of colonization and infection with an Escherichia coli strain
      producing extended-spectrum beta-lactamase (ESBL) occurred in a neonatal unit : a
      high rate of cases was observed, 27/59 neonates were colonized : one of them
      developed meningitis with favourable outcome and another baby developed
      conjunctivitis. Despite intensive efforts to control the outbreak by standard
      methods of hand hygiene, patients screening and isolation, the spread was
      uncontrolled and the unit was closed to all admission in order to stop the
      outbreak. The investigation was not able to identify a single outbreak's source.
      Emergence and spread of ESBL producing E. coli strains from community and
      hospital acquired infections are a significant public health problem with
      difficult choice of treatment for serious infections.

PMID- 20826324
TI  - [Implication of extended-spectrum beta-lactamase enterobacteriaceae in nosocomial
      infections in neonates].
AB  - AIMS: The objective of this study was to determine the incidence of extended
      spectrum beta-lactamase (ESBLS) enterobacteriaceae colonization and infection in
      hospitalized children. METHODS: This prospective study was conducted in a
      neonatal intensive care unit from 2000 to 2009. We recorded all isolations of
      ESBLs enterobacteriaceae from clinical samples that were obtained from
      hospitalized children. Anorectal samples were taken at admission and every 10
      days. We systematically recorded cases of confirmed infections that was caused by
      ESBLs enterobacteriacea. RESULTS: A total of 46 ESBL(S) pathogens (E coli 58.7 %,
      Enterobacter cloacae 10.8 %, Klebsiella Pneumonia 19.5%, K. oxytoca 6.5 %,
      Citrobacter 4.5 %) were isolated during 10 years, the global incidence was 5.1
      cases per 1000 admissions. Three infants developed nosocomial infections, E. coli
      sepsis and pneumonia and Enterobacter cloacae omphalitis. These patients were
      treated with carbapenem with significant clinical improvement. ESBLs
      enterobacteriaceae were found first in Klebsiella pneumonia and then
      predominantly in E. coli. Current efforts have focused on monitoring proper hand
      hygiene, evaluation of potential reservoirs of bacterial acquisition and
      transmission, cohorting and isolation of colonized infants, and fostering of
      effective inter- and intrahospital communication. Carbapenem seems to be safe in
      newborn and is recommended for the treatment of EBLSEs enterobacteriaceae
      infections.

PMID- 20826325
TI  - [Carbapenemases in enterobacteriaceae].
AB  - Carbapenem-hydrolyzing beta-lactamases are the most powerful mechanism of
      resistance to carbapenems. Carbapenemases have been reported extensively
      worldwide now in Enterobacteriaceae. Carbapenemases of the KPC type have been
      reported first from the USA in Klebsiella pneumoniae, then worldwide with a
      marked endemicity in Israel and Greece. Metallo-enzymes (VIM, IMP...) have been
      also reported internationnaly with high prevalence in Southern Europe and Asia.
      OXA-48 which is one of the latest carbapenemases reported differs structurally
      from the other carbapenemases and have been identified mostly from Mediterranean
      countries. These carbapenemase genes are mostly plasmid located in K. pneumoniae
      from nosocomial origin. They have been also identified as a source of community
      acquired infections. Carbapenemase producers are also multidrug resistant
      explaining the difficulty to treat infections. Detection of infected patients and
      carriers remain difficult which may explain an underlying spread with dramatic
      therapeutic consequences.

PMID- 20826326
TI  - [Pediatric use of carbapenems].
AB  - Increasing frequency of infections due to multi-drug resistant organisms is
      currently observed in the adult and pediatric population. Therapeutic options are
      unfortunately limited to treat such infections. It is the clinician's
      responsibility to use wide-spectrum antibiotics when appropriate, but also to
      limit the use of these drugs to the sole situations where such a potent treatment
      is required. Carbapenems are the most efficient beta-lactams, especially against
      gram-negative bacilli, and the most preserved from resistance so far. This review
      summarizes microbiological, pharmacokinetic and pharmacodynamic characteristics
      of currently available cabapenems. Their clinical use in different pediatric
      settings is then discussed, based on available published evidence. In order to
      maintain their microbiological efficiency and to limit the emergence of carbapem
      resistant strains, carbapenems should be exclusively used for infections due to
      gram-negative bacilli showing resistance to other beta-lactams. In the next years
      meropenem should logically replace imipenem indications regarding its superior
      pharmacokinetic-pharmacodynamic properties, its higher tolerance and its easier
      use in the pediatric population.

PMID- 20826327
TI  - [Colimycin: an old antibiotic which has to be learnt to know].
AB  - The emergence of Pseudomonas aeruginosa, Acinetobacter baumanii, and
      Enterobacteriaceae strains resistant to all beta-lactams (including
      carbapemenases producing strains), quinolones, aminoglycosides and no new
      antibiotics have led to reconsider the colimycin use. This antibiotic known since
      the 50s, had been completely abandoned, in one hand due to poor clinical activity
      and in other hand because of its toxicity (renal and neurological). The colimycin
      is an antibiotic complex like no other (until now, we have more questions than
      answers) and extremely difficult to use. It should be prescribed only when
      absolutely necessary and only after isolation of the strain responsible of the
      infection and determination of the in vitro susceptibility tests confirming both
      resistance to other antibiotics and sensitivity to colimycin. Even if the strain
      is resistant to other antibiotics, a synergy can be observed with many
      antibiotics. Monotherapy is not recommended because it promotes rapid development
      of resistance. Because of low serum concentrations, very close to MICs of
      targeted bacteria, the dosages are necessarily high.

PMID- 20826328
TI  - [Epidemiology of urinary tract infection in children in Marrakech].
AB  - By its incidence, the polymorphism of its clinical presentation, its potential
      gravity, the difficulty of realization of urine culture in children, the
      frequency of the subjacent urologic abnormalities, the urinary tract infection
      (UTI) is an important problem in paediatrics. This work relates to a
      retrospective study carrying 121 episodes of UTI in 111 children taken care in
      paediatrics services of the Teaching Hospital Mohammed VI in Marrakech between
      March 2005 and March 2009. The age of our children varied between one month and
      15 years with an average of 31 months, girls were more touched than boys with a
      sex ratio at 1.9. E. coli was the most common causative agent in our study (72
      %), followed by Klebsiella in 14 % and Proteus in 5.8 % of cases. The study of
      antimicrobial susceptibility showed that the majority of the isolates were
      resistant to amoxicilline in 2/3 of cases. Third generation cephalosporins and
      aminosides kept their effectiveness on the majority of isolates (E. coli was
      susceptible to 3GC in 91.2 % and to gentamycin in 88 %). E. coli was sensible to
      the TSU in 54.4 % of cases.

PMID- 20826329
TI  - [Gut translocation septicemia in infant].
AB  - Intestinal microbiotype necessary for life is a source of complications in
      childhood. Bacterial translocation is responsible of endogenous septicaemia and
      invasive complications. We report five cases of severe invasive infections
      associated with diarrhoea, digestive bleeding or sepsis. Biological parameters
      for inflammation are highly positive, and blood cultures reveal bacterial
      identification: salmonella enteridis, enterobacter cloacae, campylobacter jejuni,
      escherichia coli or clostridium difficile. We describe the predisposing factors
      and susceptibility status to develop translocation: invasive diarrhoea, asplenia,
      gasto-intestinal disease... All invasive infections in children require
      etiological approach with the possibility of an endogenous septicaemia (bacterial
      translocation). This approach minimises the nosocomial features undercurrent in
      these invasive infections, and leads also to other alternative preventive
      measures: antibiotic association, maintaining an enteral nutrition, pre or
      probiotic use, specific digestive decontamination.

PMID- 20826330
TI  - [Multiple brain abscesses complicating Enterobacter cloacae sepsis in a premature
      infant].
AB  - A neonatal infection with Enterobacter cloacae was diagnosed at day 21 in a
      premature infant. Five cerebral abscesses were discovered 6 days while a
      treatment with cefotaxim and amikacin was administered. We switched for axepim
      during 4 weeks and ciprofloxacin until complete regression of cerebral abscesses.
      At 13 months of age, the infant neurodevelopmental outcome was normal.
      Ciprofloxacin indications and tolerance during neonatal period are discussed.

PMID- 20826331
TI  - RAMP-ing up class-B GPCR ECD structural coverage.

PMID- 20826332
TI  - Seven lessons from one IDP structural analysis.

PMID- 20826333
TI  - Signal synthesis for a rapid response.

PMID- 20826334
TI  - Systematic bioinformatics and experimental validation of yeast complexes reduces
      the rate of attrition during structural investigations.
AB  - For high-throughput structural studies of protein complexes of composition
      inferred from proteomics data, it is crucial that candidate complexes are
      selected accurately. Herein, we exemplify a procedure that combines a
      bioinformatics tool for complex selection with in vivo validation, to deliver
      structural results in a medium-throughout manner. We have selected a set of 20
      yeast complexes, which were predicted to be feasible by either an automated
      bioinformatics algorithm, by manual inspection of primary data, or by literature
      searches. These complexes were validated with two straightforward and efficient
      biochemical assays, and heterologous expression technologies of complex
      components were then used to produce the complexes to assess their feasibility
      experimentally. Approximately one-half of the selected complexes were useful for
      structural studies, and we detail one particular success story. Our results
      underscore the importance of accurate target selection and validation in avoiding
      transient, unstable, or simply nonexistent complexes from the outset.

PMID- 20826335
TI  - Crystal structure of the ectodomain complex of the CGRP receptor, a class-B GPCR,
      reveals the site of drug antagonism.
AB  - Dysregulation of the calcitonin gene-related peptide (CGRP), a potent
      vasodilator, is directly implicated in the pathogenesis of migraine. CGRP binds
      to and signals through the CGRP receptor (CGRP-R), a heterodimer containing the
      calcitonin receptor-like receptor (CLR), a class B GPCR, and RAMP1, a receptor
      activity-modifying protein. We have solved the crystal structure of the CLR/RAMP1
      N-terminal ectodomain heterodimer, revealing how RAMPs bind to and potentially
      modulate the activities of the CLR GPCR subfamily. We also report the structures
      of CLR/RAMP1 in complex with the clinical receptor antagonists olcegepant
      (BIBN4096BS) and telcagepant (MK0974). Both drugs act by blocking access to the
      peptide-binding cleft at the interface of CLR and RAMP1. These structures
      illustrate, for the first time, how small molecules bind to and modulate the
      activity of a class B GPCR, and highlight the challenges of designing potent
      receptor antagonists for the treatment of migraine and other class B GPCR-related
      diseases.

PMID- 20826336
TI  - Structural diversity in free and bound states of intrinsically disordered protein
      phosphatase 1 regulators.
AB  - Complete folding is not a prerequisite for protein function, as disordered and
      partially folded states of proteins frequently perform essential biological
      functions. In order to understand their functions at the molecular level, we
      utilized diverse experimental measurements to calculate ensemble models of three
      nonhomologous, intrinsically disordered proteins: I-2, spinophilin, and DARPP-32,
      which bind to and regulate protein phosphatase 1 (PP1). The models demonstrate
      that these proteins have dissimilar propensities for secondary and tertiary
      structure in their unbound forms. Direct comparison of these ensemble models with
      recently determined PP1 complex structures suggests a significant role for
      transient, preformed structure in the interactions of these proteins with PP1.
      Finally, we generated an ensemble model of partially disordered I-2 bound to PP1
      that provides insight into the relationship between flexibility and biological
      function in this dynamic complex.

PMID- 20826337
TI  - Monomerization of viral entry inhibitor griffithsin elucidates the relationship
      between multivalent binding to carbohydrates and anti-HIV activity.
AB  - Mutations were introduced to the domain-swapped homodimer of the antiviral lectin
      griffithsin (GRFT). Whereas several single and double mutants remained dimeric,
      insertion of either two or four amino acids at the dimerization interface
      resulted in a monomeric form of the protein (mGRFT). Monomeric character of the
      modified proteins was confirmed by sedimentation equilibrium ultracentrifugation
      and by their high resolution X-ray crystal structures, whereas their binding to
      carbohydrates was assessed by isothermal titration calorimetry. Cell-based
      antiviral activity assays utilizing different variants of mGRFT indicated that
      the monomeric form of the lectin had greatly reduced activity against HIV-1,
      suggesting that the antiviral activity of GRFT stems from crosslinking and
      aggregation of viral particles via multivalent interactions between GRFT and
      oligosaccharides present on HIV envelope glycoproteins. Atomic resolution crystal
      structure of a complex between mGRFT and nonamannoside revealed that a single
      mGRFT molecule binds to two different nonamannoside molecules through all three
      carbohydrate-binding sites present on the monomer.

PMID- 20826338
TI  - Computational design of epitope-scaffolds allows induction of antibodies specific
      for a poorly immunogenic HIV vaccine epitope.
AB  - Broadly cross-reactive monoclonal antibodies define epitopes for vaccine
      development against HIV and other highly mutable viruses. Crystal structures are
      available for several such antibody-epitope complexes, but methods are needed to
      translate that structural information into immunogens that re-elicit similar
      antibodies. We describe a general computational method to design epitope
      scaffolds in which contiguous structural epitopes are transplanted to scaffold
      proteins for conformational stabilization and immune presentation. Epitope
      scaffolds designed for the poorly immunogenic but conserved HIV epitope 4E10
      exhibited high epitope structural mimicry, bound with higher affinities to
      monoclonal antibody (mAb) 4E10 than the cognate peptide, and inhibited HIV
      neutralization by HIV+ sera. Rabbit immunization with an epitope-scaffold induced
      antibodies with structural specificity highly similar to mAb 4E10, an important
      advance toward elicitation of neutralizing activity. The results demonstrate that
      computationally designed epitope-scaffolds are valuable as structure-specific
      serological reagents and as immunogens to elicit antibodies with predetermined
      structural specificity.

PMID- 20826339
TI  - Structural insight into the zinc finger CW domain as a histone modification
      reader.
AB  - The zinc finger CW (zf-CW) domain is a motif of about 60 residues that is
      frequently found in proteins involved in epigenetic regulation. Here, we
      determined the NMR solution structure of the zf-CW domain of the human zf-CW and
      PWWP domain containing protein 1 (ZCWPW1). The zf-CW domain adopts a new fold in
      which a zinc ion is coordinated tetrahedrally by four conserved Cys ligand
      residues. The tertiary structure of the zf-CW domain partially resembles that
      adopted by the plant homeo domain (PHD) finger bound to the histone tail,
      suggesting that the zf-CW domain and the PHD finger have similar functions. The
      solution structure of the complex of the zf-CW domain with the histone H3 tail
      peptide (1-10) with trimethylated K4 clarified its binding mode. Our structural
      and biochemical studies have identified the zf-CW domain as a member of the
      histone modification reader modules for epigenetic regulation.

PMID- 20826340
TI  - Metal-binding sites are designed to achieve optimal mechanical and signaling
      properties.
AB  - Many proteins require bound metals to achieve their function. We take advantage
      of increasing structural data on metal-binding proteins to elucidate three
      properties: the involvement of metal-binding sites in the global dynamics of the
      protein, predicted by elastic network models, their exposure/burial to solvent,
      and their signal-processing properties indicated by Markovian stochastics
      analysis. Systematic analysis of a data set of 145 structures reveals that the
      residues that coordinate metal ions enjoy remarkably efficient and precise signal
      transduction properties. These properties are rationalized in terms of their
      physical properties: participation in hinge sites that control the softest modes
      collectively accessible to the protein and occupancy of central positions
      minimally exposed to solvent. Our observations suggest that metal-binding sites
      may have been evolutionary selected to achieve optimum allosteric communication.
      They also provide insights into basic principles for designing metal-binding
      sites, which are verified to be met by recently designed de novo metal-binding
      proteins.

PMID- 20826341
TI  - Structure and cellular roles of the RMI core complex from the bloom syndrome
      dissolvasome.
AB  - BLM, the protein product of the gene mutated in Bloom syndrome, is one of five
      human RecQ helicases. It functions to separate double Holliday junction DNA
      without genetic exchange as a component of the "dissolvasome," which also
      includes topoisomerase IIIalpha and the RMI (RecQ-mediated genome instability)
      subcomplex (RMI1 and RMI2). We describe the crystal structure of the RMI core
      complex, comprising RMI2 and the C-terminal OB domain of RMI1. The overall RMI
      core structure strongly resembles two-thirds of the trimerization core of the
      eukaryotic single-stranded DNA-binding protein, Replication Protein A.
      Immunoprecipitation experiments with RMI2 variants confirm key interactions that
      stabilize the RMI core interface. Disruption of this interface leads to a
      dramatic increase in cellular sister chromatid exchange events similar to that
      seen in BLM-deficient cells. The RMI core interface is therefore crucial for BLM
      dissolvasome assembly and may have additional cellular roles as a docking hub for
      other proteins.

PMID- 20826343
TI  - Quantitative structural analysis of importin-beta flexibility: paradigm for
      solenoid protein structures.
AB  - The structure of solenoid proteins facilitates a higher degree of flexibility
      than most folded proteins. In importin-beta, a nuclear import factor built from
      19 tandem HEAT repeats, flexibility plays a crucial role in allowing interactions
      with a range of different partners. We present a comprehensive analysis of
      importin-beta flexibility based on a number of different approaches. We
      determined the crystal structure of unliganded Saccharomyces cerevisiae importin
      beta (Kap95) to allow a quantitative comparison with importin-beta bound to
      different partners. Complementary mutagenesis, small angle X-ray scattering and
      molecular dynamics studies suggest that the protein samples several conformations
      in solution. The analyses suggest the flexibility of the solenoid is generated by
      cumulative small movements along its length. Importin-beta illustrates how
      solenoid proteins can orchestrate protein interactions in many cellular pathways.

PMID- 20826342
TI  - Crystal structures of RMI1 and RMI2, two OB-fold regulatory subunits of the BLM
      complex.
AB  - Mutations in BLM, a RecQ-like helicase, are linked to the autosomal recessive
      cancer-prone disorder Bloom's syndrome. BLM associates with topoisomerase (Topo)
      IIIalpha, RMI1, and RMI2 to form the BLM complex that is essential for genome
      stability. The RMI1-RMI2 heterodimer stimulates the dissolution of double
      Holliday junction into non-crossover recombinants mediated by BLM-Topo IIIalpha
      and is essential for stabilizing the BLM complex. However, the molecular basis of
      these functions of RMI1 and RMI2 remains unclear. Here we report the crystal
      structures of multiple domains of RMI1-RMI2, providing direct confirmation of the
      existence of three oligonucleotide/oligosaccharide binding (OB)-folds in RMI1
      RMI2. Our structural and biochemical analyses revealed an unexpected insertion
      motif in RMI1N-OB, which is important for stimulating the dHJ dissolution. We
      also revealed the structural basis of the interaction between RMI1C-OB and RMI2
      OB and demonstrated the functional importance of the RMI1-RMI2 interaction in
      genome stability maintenance.

PMID- 20826344
TI  - Structure and functional regulation of RipA, a mycobacterial enzyme essential for
      daughter cell separation.
AB  - Cell separation depends on cell-wall hydrolases that cleave the peptidoglycan
      layer connecting daughter cells. In Mycobacterium tuberculosis, this process is
      governed by the predicted endopeptidase RipA. In the absence of this enzyme, the
      bacterium is unable to divide and exhibits an abnormal phenotype. We here report
      the crystal structure of a relevant portion of RipA, containing its catalytic
      domain and an extra-domain of hitherto unknown function. The structure clearly
      demonstrates that RipA is produced as a zymogen, which needs to be activated to
      achieve cell-division. Bacterial cell-wall degradation assays and proteolysis
      experiments strongly suggest that activation occurs via proteolytic processing of
      a fully solvent exposed loop identified in the crystal structure. Indeed,
      proteolytic cleavage at this loop produces an activated form, consisting of the
      sole catalytic domain. Our work provides the first evidence of self-inhibition in
      cell-disconnecting enzymes and opens a field for the design of novel
      antitubercular therapeutics.

PMID- 20826345
TI  - Structure of the PTEN-like region of auxilin, a detector of clathrin-coated
      vesicle budding.
AB  - Auxilin, a J-domain containing protein, recruits the Hsc70 uncoating ATPase to
      newly budded clathrin-coated vesicles. The timing of auxilin arrival determines
      that uncoating will commence only after the clathrin lattice has fully assembled
      and after membrane fission is complete. Auxilin has a region resembling PTEN, a
      PI3P phosphatase. We have determined the crystal structure of this region of
      bovine auxilin 1; it indeed resembles PTEN closely. A change in the structure of
      the P loop accounts for the lack of phosphatase activity. Inclusion of
      phosphatidylinositol phosphates substantially enhances liposome binding by wild
      type auxilin, but not by various mutants bearing changes in loops of the C2
      domain. Nearly all these mutations also prevent recruitment of auxilin to newly
      budded coated vesicles. We propose a specific geometry for auxilin association
      with a membrane bilayer and discuss implications of this model for the mechanism
      by which auxilin detects separation of a vesicle from its parent membrane.

PMID- 20826346
TI  - Structural basis of the sensor-synthase interaction in autoinduction of the
      quorum sensing signal DSF biosynthesis.
AB  - The diffusible signal factor (DSF)-dependent quorum sensing (QS) system adopts a
      novel protein-protein interaction mechanism to autoregulate the production of
      signal DSF. Here, we present the crystal structures of DSF synthase RpfF and its
      complex with the REC domain of sensor protein RpfC. RpfF is structurally
      similarity to the members of the crotonase superfamily and contains an N-terminal
      alpha/beta spiral core domain and a C-terminal alpha-helical region. Further
      structural and mutational analysis identified two catalytic glutamate residues,
      which is the conserved feature of the enoyl-CoA hydratases/dehydratases. A
      putative substrate-binding pocket was unveiled and the key roles of the residues
      implicated in substrate binding were verified by mutational analysis. The binding
      of the REC domain may lock RpfF in an inactive conformation by blocking the
      entrance of substrate binding pocket, thereby negatively regulating DSF
      production. These findings provide a structural model for the RpfC-RpfF
      interaction-mediated QS autoinduction mechanism.

PMID- 20826349
TI  - Subarachnoid hemorrhage in a 13-year-old girl.
AB  - At 5:20 pm, a local flight team was activated to respond for an interfacility
      transfer of a 13-year-old girl with a subarachnoid hemorrhage. In the history
      obtained, the patient's parents noted that she had not been feeling well for the
      past several days. She had been complaining of intermittent dizziness and a
      persistent headache. Until the onset of these prodromal events, she had been
      active with no medical history. That afternoon, the child was playing with her
      friends at the school playground. As the group was walking home, they noticed
      that the patient was not with them. They subsequently returned and found her
      lying face-down in the bushes, unresponsive, with agonal respirations.

PMID- 20826350
TI  - Certification review.

PMID- 20826351
TI  - You can't take it with you.

PMID- 20826347
TI  - PagP crystallized from SDS/cosolvent reveals the route for phospholipid access to
      the hydrocarbon ruler.
AB  - Enzymatic reactions involving bilayer lipids occur in an environment with strict
      physical and topological constraints. The integral membrane enzyme PagP transfers
      a palmitoyl group from a phospholipid to lipid A in order to assist Escherichia
      coli in evading host immune defenses during infection. PagP measures the
      palmitoyl group with an internal hydrocarbon ruler that is formed in the interior
      of the eight-stranded antiparallel beta barrel. The access and egress of the
      palmitoyl group is thought to take a lateral route from the bilayer phase to the
      barrel interior. Molecular dynamics, mutagenesis, and a 1.4 A crystal structure
      of PagP in an SDS / 2-methyl-2,4-pentanediol (MPD) cosolvent system reveal that
      phospholipid access occurs at the crenel present between strands F and G of PagP.
      In this way, the phospholipid head group can remain exposed to the cell exterior
      while the lipid acyl chain remains in a predominantly hydrophobic environment as
      it translocates to the protein interior.

PMID- 20826353
TI  - The buck stops here.

PMID- 20826354
TI  - 2010 Critical Care Transport Workplace and Salary Survey.
AB  - Critical care transport (CCT) leaders and managers from 300 organizations were
      invited to participate in an online survey (participation rate, 34%) with
      approximately 150 questions covering a broad base of CCT organizational,
      workplace, personnel, and salary matters. In addition to medical team
      composition, recruitment and retention, training, education, and benefits, the
      survey presents CCT crew salary data by job class by Bowley's seven-figure
      summary, as well as average, minimum, and maximum hourly rates. Salaries are
      reported in a national aggregate and by Association of Air Medical Services
      region.

PMID- 20826355
TI  - Health Care District of Palm Beach County's Air Medical Program and Trauma
      System.

PMID- 20826356
TI  - Miami Children's Hospital LifeFlight: setting a high standard for patient
      transport safety and service.

PMID- 20826358
TI  - En-route decision point protocols: when discretion is the better part of valor.

PMID- 20826359
TI  - Air medical transport curriculum provides education for medical students.
AB  - INTRODUCTION: Increased regionalization of healthcare will most likely result in
      greater utilization of air medical transport (AMT). Education of providers
      regarding the utilization and capabilities of AMT will be important. This study
      was undertaken to determine whether our curriculum in AMT provided a useful and
      satisfying educational experience for medical students METHODS: The curriculum
      included three 6-hour fly-along sessions, 2 hours of lectures, 2 hours of case
      review, an 80-page syllabus listing articles and position papers, and a 3-page
      writing assignment. The study was a review of the participants' (1st- and 2nd
      year medical students) test scores and postelective evaluation for 1 year. The
      setting was a two-helicopter AMT program based at an urban, university-affiliated
      level 1 trauma center. Twelve students (1/month) participated in the month-long
      elective. The students took a 20-item test before and after the elective and a 15
      item postelective evaluation (5-point scale: very dissatisfied, dissatisfied,
      neutral, satisfied, very satisfied). A paired t-test was used to compare the mean
      pre-test and mean post-test scores. The evaluation data were analyzed
      descriptively. RESULTS: The mean number of correct responses on the post-test (M
      = 18.67, SD = 1.61) was significantly higher than the mean number of correct
      responses on the pretest (M = 13.83, SD = 2.17), P < .001. All students were
      either satisfied (56%) or very satisfied (44%) with the lectures and case review.
      Eleven (91%) were very satisfied with interaction with the crew, and nine (75%)
      were very satisfied overall (25% satisfied). Seven (58%) were very likely to use
      AMT in their career, two (16.7%) likely, two (16.7%) unsure, and one (8.3%)
      unlikely. CONCLUSIONS: Our curriculum in AMT provided a useful and satisfying
      educational opportunity for medical students. Their knowledge of AMT increased,
      and all were satisfied or very satisfied with the didactics and the crew
      interaction. Most thought that they would use AMT in their career.

PMID- 20826360
TI  - Tribological properties of Ti-based alloys in a simulated bone-implant interface
      with Ringer's solution at fretting contacts.
AB  - The wear properties of oxidized and non-oxidized gamma-TiAl (a potential
      biomaterial) as well as Ti-6Al-4V and CP-Ti disks were studied and characterized
      by means of standard wear tests using a custom made bone pin arrangement. The Ti
      based disks were oxidized in air at 500 and 800 degrees C for one hour. The
      tribological properties of the oxides formed over the disks were studied using a
      linear reciprocating wear testing machine under both dry and simulated biological
      conditions using Ringer's solution. Loss of metal oxide and coefficient of
      friction values were determined from wear testing. From the results, abrasion and
      adhesion were the primary wear mechanisms in each of the three alloy-bone pairs.
      Specifically, the oxide formed on gamma-TiAl possessed the highest COF and wear
      resistance of the three materials which were studied. Also, as expected, bone
      wears down faster than the Ti-based metal oxide.

PMID- 20826361
TI  - Synthesis and characterisation of a new superelastic Ti-25Ta-25Nb biomedical
      alloy.
AB  - In this study, a new Ti-25Ta-25Nb (mass%) beta alloy was synthesised by cold
      crucible semi-levitation melting. This technique made it possible to obtain
      homogeneous ingots although the elements used have very different melting points.
      After melting, a thermo-mechanical treatment was applied in order to obtain a
      perfectly recrystallised beta microstructure. For this alloy composition, the
      tensile tests showed a very low Young's modulus associated with an important
      super-elastic behaviour, which contributes to decrease the elastic modulus under
      stress and to increase the recoverable strain. On the other hand, the corrosion
      tests, which were carried out in a neutral Ringer solution, indicated a corrosion
      resistance higher than that of the commercially pure CP Ti alloy. These results
      show that this new alloy possesses all the characteristics necessary for its long
      term use in medical implants.

PMID- 20826362
TI  - Mechanical properties of low modulus beta titanium alloys designed from the
      electronic approach.
AB  - Titanium alloys dedicated to biomedical applications may display both clinical
      and mechanical biocompatibility. Based on nontoxic elements such as Ti, Zr, Nb,
      Ta, they should combine high mechanical resistance with a low elastic modulus
      close to the bone elasticity (E=20 GPa) to significantly improve bone remodelling
      and osseointegration processes. These elastic properties can be reached using
      both lowering of the intrinsic modulus by specific chemical alloying and
      superelasticity effects associated with a stress-induced phase transformation
      from the BCC metastable beta phase to the orthorhombic alpha(") martensite. It is
      shown that the stability of the beta phase can be triggered using a chemical
      formulation strategy based on the electronic design method initially developed by
      Morinaga. This method is based on the calculation of two electronic parameters
      respectively called the bond order (B(o)) and the d orbital level (M(d)) for each
      alloy. By this method, two titanium alloys with various tantalum contents, Ti
      29Nb-11Ta-5Zr and Ti-29Nb-6Ta-5Zr (wt%) were prepared. In this paper, the effect
      of the tantalum content on the elastic modulus/yield strength balance has been
      investigated and discussed regarding the deformation modes. The martensitic
      transformation beta-->alpha(") has been observed on Ti-29Nb-6Ta-5Zr in contrast
      to Ti-29Nb-11Ta-5Zr highlighting the chemical influence of the Ta element on the
      initial beta phase stability. A formulation strategy is discussed regarding the
      as-mentioned electronic parameters. Respective influence of cold rolling and
      flash thermal treatments (in the isothermal omega phase precipitation domain) on
      the tensile properties has been investigated.

PMID- 20826363
TI  - Preparation and characterization of NaOH treated micro-fibrous polyethylene
      terephthalate nonwovens for biomedical application.
AB  - Recently, micro-fibrous polyethylene terephthalate nonwovens have been
      investigated and applied in many biotechnological and biomedical applications.
      NaOH treatment has been used as a simple and cost effective method to alter
      surface properties, in order to overcome their surface inertness. However, the
      effects of this treatment on the matrices mechanical and physical properties;
      particularly, those composed of fibers with small diameter (<20 microm); have
      been poorly investigated. This study investigates the variations, imposed by the
      NaOH treatment, in the physical and tensile properties of micro-fibrous
      polyethylene terephthalate mats. Polyethylene terephthalate webs with two
      different average fiber diameters of 6+/-2.5 and 10+/-4 microm were produced by
      melt blowing process. A number of these webs were consolidated to prepare fibrous
      matrices using a thermal treatment. The matrices were treated using NaOH 1 N at
      65 degrees C for various durations (ranging from 20 min to 24 h). In addition to
      their physical properties such as weight loss, thickness, porosity, shrinkage and
      surface density; their morphology and tensile properties were also evaluated
      using scanning electron microscopy and micromechanical tester, respectively. In
      general, by increasing treatment duration, weight loss, porosity, and shrinkage
      increased, while thickness and density decreased. As a result of treatment
      duration, pores appeared on the surface of individual fibers, and tensile stress
      and Young's modulus decreased while tensile strain increased. Mats with different
      fiber diameters showed different physical and mechanical properties. These
      findings suggested that the structure of the matrices and the properties required
      for its end use, for biomedical applications including scaffolding materials for
      tissue engineering, should be considered in selecting NaOH treatment condition.

PMID- 20826364
TI  - A multiscale modeling approach to scaffold design and property prediction.
AB  - The optimum scaffold architecture for bone tissue regeneration is a porous
      structure with a narrow range of pore sizes, pore density, and a high degree of
      interconnectivity among pores. To achieve such a design, the microstructure of
      the scaffold material must be optimized in order to satisfy both biological and
      mechanical function requirements. In this paper, we present a multiscale modeling
      approach for designing a scaffold with an optimized porosity and mechanical
      properties made from a two-phase composite of spherical hydroxyapatite (HAp)
      particles embedded in a collagen matrix. In particular, first-principles
      computation is used to calculate the elastic properties and theoretical strengths
      of nanoscaled HAp particles. The constitutive properties of the HAp/collagen
      composites are subsequently computed as a function of HAp content via FEM-based
      micromechanical modeling. The constitutive relations of the composite are then
      utilized to optimize the mechanical properties of a three-dimensional scaffold
      for either cortical or cancellous bone by varying the pore size, pore density and
      volume fractions of HAp in the composite. For the pore size, pore density, volume
      fractions of HAp considered, the scaffold can be designed to match the mechanical
      properties of cancellous bone, but not those of cortical bone. The optimized
      scaffold is one with a pore diameter of 1000 microm, a channel diameter of 100
      microm, 27% pore density and at least 20% HAp by volume.

PMID- 20826365
TI  - Conversion degree, microhardness, microleakage and fluoride release of different
      fissure sealants.
AB  - The purpose of this study was to determine the degree of conversion (DC),
      microhardness, microleakage and fluoride release of a nano-filled resin based
      fissure sealant (Grandio Seal, GS) and compare it with an un-filled resin based
      fissure sealant (Clinpro, CL) and a glass-ionomer based fissure sealant (Fuji
      Triage, FT). Disk shaped specimens were prepared from tested fissure sealants to
      determine the DC, Vicker hardness (VHN) and fluoride release (FR). The DC and VHN
      of each material was evaluated after 24 h. The cumulative fluoride concentrations
      were evaluated at 1 h, 6 h, 12 h, 1, 7, 15 and 30 days. For microleakage
      evaluation, fissure sealants were applied to the etched and dried enamel surfaces
      of sound third molar teeth according to the manufacturer's instructions (n=10).
      After the thermocycling and mechanical loading procedures, microleakage
      assessments were carried out. Data were analyzed using one-way ANOVA followed by
      a post hoc Tukey test, the Kruskal Wallis and Mann-Whitney U test (p<0.05).
      Results revealed differences regarding DC between all groups: FT (89%) > GS
      (55.02%) > CL (%51.10) (p<0.05). The VHN values were significantly different
      among all groups in the following order: GS > FT > CL (p<0.05). FT exhibited
      significantly higher microleakage scores compared to the CL and GS sealants
      (p<0.05). The FR of FT was significantly greater than CL and GS (p<0.05). Nano
      filled resin based sealant can be used as an alternative to other fissure sealant
      materials because of its superior hardness results and feasible sealing ability.

PMID- 20826366
TI  - Spatially varying properties of the vocal ligament contribute to its
      eigenfrequency response.
AB  - The vocal ligament is known to have nonlinear variation in geometry, yet this is
      rarely considered in empirical or computational studies. This paper investigates
      the effects of a nonlinear variation of the anterior-to-posterior geometry and
      the corresponding spatial variation in elastic modulus on the fundamental
      frequency of vibration for the vocal ligament. Uniaxial tensile tests were
      performed on a vocal ligament specimen dissected from an excised 60-year-old male
      larynx. Digital image correlation (DIC) was used to obtain the spatial
      deformation field for the entire ligament specimen. DIC results revealed that the
      tensile deformation was very heterogeneous, with the least amount of deformation
      occurring in the region of smallest cross-sectional area. The elastic modulus was
      calculated locally and was found to be approximately 10 times higher at the
      midpoint of the vocal ligament than in the anterior and posterior macula flavae
      regions. Based on the spatially varying material properties obtained, finite
      element models (isotropic and transversely isotropic) were created to investigate
      how the effects of varying cross-section, heterogeneous stiffness, and anisotropy
      could affect the fundamental frequency of vibration. It was found that the
      spatial cross-section variation and the spatially varying anisotropy (i.e.
      modulus ratio) are significant to predictions of the vibration characteristics.
      Fundamental frequencies predicted with a finite element model are discussed in
      view of rotatory inertia and contribution of transverse shear deformation.

PMID- 20826367
TI  - Evaluation of an experimental dental porcelain.
AB  - The aim of this study was to evaluate fracture toughness, hardness, ceramic/metal
      bond strength and microstructure of experimental dental porcelain and compare it
      with commercial type. Specimens of specific dimensions were prepared. Fracture
      toughness was assessed by a three-point bending test. The Vickers hardness was
      measured using a microhardness tester. The ceramometal bond strength was measured
      using a universal testing machine. The load was applied at the porcelain/metal
      interface via a chisel edged blade with a crosshead speed of 2.0 mm/min until
      fracture. The polished specimens of dental porcelain were chemically etched and
      the microstructure was analyzed with a scanning electron microscope. The results
      showed comparable fracture toughness and bond strength for both materials, while
      the experimental porcelain exhibited higher hardness. The experimental porcelain
      showed uniform cohesive failure while the commercial type showed mixed mode of
      failure. The microstructure of the experimental porcelain was tetragonal leucite
      crystals dispersed randomly in a glass matrix. The leucite crystals exist in two
      forms, acicular and rod like structures. It was concluded that the experimental
      porcelain has adequate fracture toughness and ceramic/metal bond strength that
      can resist the rapid crack propagation and its consequent catastrophic failure,
      which indicates a material serviceability in the oral cavity.

PMID- 20826368
TI  - Failure analysis of a total hip prosthesis implanted in active patient.
AB  - This work presents an analysis of a total hip prosthesis that failed in service
      prematurely within 5 years. The prosthesis presented a fractured stem that was
      extracted from a 46 year old male patient, 75 kg weight and 1.76 m height. In
      order to determine the origin of the failure, the femoral stem component was
      analyzed by means of visual inspection; optical microscope (OM), scanning
      electronic microscopy (SEM) and energy disperse spectroscopy (EDS). The
      investigation showed that the crack had originated due to a high stress
      concentration on the anterolateral corner section of the stem. Any discontinuity
      or defect on the prosthesis surface in this location acted as preferential site
      to nucleate a crack which propagated by fatigue until the cross section was not
      able to sustain an eventual high load produced for the active patient.

PMID- 20826370
TI  - Dehydration effect on the mechanical behaviour of biological soft tissues:
      observations on kidney tissues.
AB  - This paper deals with the effects of dehydration on the mechanical properties of
      biological soft tissues and with the validity of methods used in previous works
      such as a coat of petroleum jelly or silicon oil to minimise the drying of the
      tissue during mechanical testing. We find that the samples get stiffer as they
      dry but that this phenomenon is wholly reversible upon re-hydrating the samples.
      A bath of saline solution is the best hydration method but a coat of low
      viscosity silicon oil around the free edge of the sample also proves to be a good
      anti-drying method. However, using petroleum jelly to prevent tissue dehydration
      should be banned because the jelly largely contributes to the measured mechanical
      moduli.

PMID- 20826369
TI  - Fractographic analysis of a dental zirconia framework: a case study on design
      issues.
AB  - Fractographic analysis of clinically failed dental ceramics can provide insights
      as to the failure origin and related mechanisms. One anterior 6-unit all-ceramic
      zirconia fixed partial denture (FPD) (Cercon) has been clinically recovered and
      examined using qualitative fractography. The purpose was to identify the fracture
      origin and to state the reasons for failure. The recovered parts of the zirconia
      FPD were microscopically examined to identify classic fractographic patterns such
      as arrest lines, hackle, twist hackle and wake hackle. The direction of crack
      propagation was mapped and interpreted back to the origin of failure at the
      interface of the occlusal-palatal tip of the core and the veneering ceramic. An
      inappropriate core drop design favoring localized stress concentration combined
      with a pore cluster in the veneering ceramic at the core tip interface were the
      reasons for this premature through-the-core thickness failure.

PMID- 20826371
TI  - Comparative study of the fatigue strength of five acrylic denture resins.
AB  - The aim of this in vitro study was to compare the fatigue resistance of three
      kinds of heat-polymerized acrylic resins (conventional heat-polymerized, rapid
      heat-polymerized, high impact acrylic resin), a kind of visible light-cured resin
      and a kind of self-cured acrylic resin. A total of 60 notched and un-notched
      specimens (65 mm x 10 mm x 3 mm) were fabricated, 12 from each material. The
      fatigue resistance was measured by applying repeated three-point bending
      deflection to the specimens. For statistical analysis, Kruskal-Wallis test
      followed by Dunn's multiple comparison tests were used. The Kruskal-Wallis test
      revealed significant differences in the fatigue resistance among some groups
      (p<0.05). Conventional- and rapid-heat polymerized resins had lower fatigue
      resistance values than heat-polymerized high impact acrylic resin, but the
      differences were statistically non-significant according to Dunn's test (p>0.05).
      High impact acrylic resin was also found to have significantly higher fatigue
      resistance value than that of self-cured resin and light-cured resin (p<0.05).
      Further, there was no statistically significant difference between the mean
      fatigue resistance value of visible light-cured resin and self-cured resin
      (p>0.05).

PMID- 20826372
TI  - The micromechanical behavior of lyophilized glutaraldehyde-treated bovine
      pericardium under uniaxial tension.
AB  - The micromechanical behavior of lyophilized glutaraldehyde bovine pericardium
      undergoing uniaxial tension was studied by digital image correlation. The
      experiments were conducted simultaneously at macromechanical and micromechanical
      levels, to correlate the mechanical response of this biomaterial at different
      scales. From the experiments, displacement and force data were acquired; in
      addition, an image sequence of each sample surface was registered with a high
      definition camera. With the images, it was possible to obtain the vector
      displacement field between pairs of images and then the in-plane strain was
      calculated. The secant and final moduli of this material were obtained at
      macromechanical and micromechanical levels. A good agreement between the micro
      and macro moduli was observed. This analysis is a useful alternative technique
      for studying this biomaterial when local properties are needed for medical
      applications.

PMID- 20826373
TI  - Endocrine profiling and prioritization of environmental chemicals using ToxCast
      data.
AB  - BACKGROUND: The prioritization of chemicals for toxicity testing is a primary
      goal of the U.S. Environmental Protection Agency (EPA) ToxCastTM program. Phase I
      of ToxCast used a battery of 467 in vitro, high-throughput screening assays to
      assess 309 environmental chemicals. One important mode of action leading to
      toxicity is endocrine disruption, and the U.S. EPA's Endocrine Disruptor
      Screening Program (EDSP) has been charged with screening pesticide chemicals and
      environmental contaminants for their potential to affect the endocrine systems of
      humans and wildlife. OBJECTIVE: The goal of this study was to develop a flexible
      method to facilitate the rational prioritization of chemicals for further
      evaluation and demonstrate its application as a candidate decision-support tool
      for EDSP. METHODS: Focusing on estrogen, androgen, and thyroid pathways, we
      defined putative endocrine profiles and derived a relative rank or score for the
      entire ToxCast library of 309 unique chemicals. Effects on other nuclear
      receptors and xenobiotic metabolizing enzymes were also considered, as were
      pertinent chemical descriptors and pathways relevant to endocrine-mediated
      signaling. RESULTS: Combining multiple data sources into an overall, weight-of
      evidence Toxicological Priority Index (ToxPi) score for prioritizing further
      chemical testing resulted in more robust conclusions than any single data source
      taken alone. CONCLUSIONS: Incorporating data from in vitro assays, chemical
      descriptors, and biological pathways in this prioritization schema provided a
      flexible, comprehensive visualization and ranking of each chemical's potential
      endocrine activity. Importantly, ToxPi profiles provide a transparent
      visualization of the relative contribution of all information sources to an
      overall priority ranking. The method developed here is readily adaptable to
      diverse chemical prioritization tasks.

PMID- 20826374
TI  - Protective role of interleukin-10 in ozone-induced pulmonary inflammation.
AB  - BACKGROUND: The mechanisms underlying ozone (O3)-induced pulmonary inflammation
      remain unclear. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is
      known to inhibit inflammatory mediators. OBJECTIVES: We investigated the
      molecular mechanisms underlying interleuken-10 (IL-10)-mediated attenuation of O3
      induced pulmonary inflammation in mice. METHODS: Il10-deficient (Il10(-/-)) and
      wild-type (Il10(+/+)) mice were exposed to 0.3 ppm O3 or filtered air for 24, 48,
      or 72 hr. Immediately after exposure, differential cell counts and total protein
      (a marker of lung permeability) were assessed from bronchoalveolar lavage fluid
      (BALF). mRNA and protein levels of cellular mediators were determined from lung
      homogenates. We also used global mRNA expression analyses of lung tissue with
      Ingenuity Pathway Analysis to identify patterns of gene expression through which
      IL-10 modifies O3-induced inflammation. RESULTS: Mean numbers of BALF
      polymorphonuclear leukocytes (PMNs) were significantly greater in Il10(-/-) mice
      than in Il10(+/+) mice after exposure to O3 at all time points tested. O3
      enhanced nuclear NF-kappaB translocation was elevated in the lungs of Il10(-/-)
      compared with Il10(+/+) mice. Gene expression analyses revealed several IL-10
      dependent and O3-dependent mediators, including macrophage inflammatory protein
      2, cathepsin E, and serum amyloid A3. CONCLUSIONS: Results indicate that IL-10
      protects against O3-induced pulmonary neutrophilic inflammation and cell
      proliferation. Moreover, gene expression analyses identified three response
      pathways and several genetic targets through which IL-10 may modulate the innate
      and adaptive immune response. These novel mechanisms of protection against the
      pathogenesis of O3-induced pulmonary inflammation may also provide potential
      therapeutic targets to protect susceptible individuals.

PMID- 20826375
TI  - Estrogenic activity of bisphenol A and 2,2-bis(p-hydroxyphenyl)-1,1,1
      trichloroethane (HPTE) demonstrated in mouse uterine gene profiles.
AB  - BACKGROUND: Interest and concern regarding potentially estrogenic substances have
      resulted in development of model systems to evaluate mechanisms of such
      chemicals. Microarray studies have indicated that estradiol (E2)-stimulated
      uterine responses can be divided into early and late phases. Comparison of E2
      uterine transcript profiles and those of other estrogenic chemicals of interest
      in vivo indicates mechanisms and activities of test compounds. OBJECTIVES: We
      compared transcript responses and mechanisms of response using mouse reproductive
      tracts after treatment with E2, estriol (E3), bisphenol A (BPA), and 2,2-bis(p
      hydroxyphenyl)-1,1,1-trichloroethane (HPTE). METHODS: Uterine RNA from
      ovariectomized wild-type mice, estrogen receptor alpha (ERalpha) knockout
      (alphaERKO) mice, and mice expressing a DNA-binding-deficient ERalpha (KIKO)
      treated with E2, E3, BPA, or HPTE for 2 or 24 hr was analyzed by microarray.
      Resulting regulated transcripts were compared by hierarchical clustering and
      correlation analysis, and response patterns were verified by reverse
      transcription real-time polymerase chain reaction (RT-PCR). RESULTS: Both
      xenoestrogens, BPA and HPTE, showed profiles highly correlated to that of E2 in
      the early response phase (2 hr), but the correlation diminished in the later
      response phase (24 hr), similar to the known weak estrogen E3. Both xenoestrogens
      also mimicked E2 in samples from KIKO mice, indicating that they are able to
      utilize the indirect tethering mode of ERalpha signaling. No response was
      detected in ERalpha-null uteri, indicating that ERalpha mediates the responses.
      CONCLUSION: Our study forms a basis on which patterns of response and molecular
      mechanisms of potentially estrogenic chemicals can be assessed.

PMID- 20826376
TI  - [Hepatitis C virus infection and hepatocarcinogenesis].
AB  - It is evidenced that both HBV and HCV infections may cause chronic hepatitis,
      liver cirrhosis and hepatocellular carcinoma (HCC). HCV is considered as an
      oncogen virus. The mechanism of carcinogenesis in case of the two distinct
      viruses shows a number of common and different features. HCC usually develops in
      stage of liver cirrhosis caused by chronic inflammation of many years or decades.
      In contrast to HBC, HCV will not be incorporated into the genome of hepatocytes.
      It induces throughout different mechanisms the development of cancer cells, which
      will proliferate out of control. Before the discovery of HCV, the connection of
      non-A non-B (NANB) hepatitis and liver cancer has yet been observed. The
      subsequent epidemiological studies confirmed this association. A number of
      publications prove that HCC may develop without cirrhosis in HCV infected
      patients. The exact mechanism is not known, but data indicate that some proteins
      of the virus may induce oncogenic process. Differences were found in HCV core
      gene between HCC patients with and without cirrhosis. It is postulated that the
      virus evolves its oncogenic effect via endoplasmic and oxidative stress, further
      on by activation of different oncogenic signal pathways. Recent publications
      indicate the role of virus induced insulin resistance. Besides the virus
      determined factors, the host reaction, the deficient tumor cell eliminating
      capacity may also have a role in the development of liver carcinoma. Monitoring
      of HCV infected patients for HCC is an important clinical issue. Most relevant is
      the regular ultrasound cheek up. Serum alpha fetoprotein level is elevated only
      in a smaller proportion of the patients. The treatment protocol of HCV induced
      HCC does not differ from the others developed in non-HCV liver diseases.

PMID- 20826377
TI  - [Practice of treatment restriction in Hungarian intensive care units].
AB  - End of life decisions affect most of patients in intensive care units, thus, it
      is important to know both local and international practice in accordance with law
      and ethical principles for intensive care physicians. AIM: To search for local
      customs of end of life decisions (withholding or withdrawing the therapy,
      shortening of the dying process), and to compare the data with the international
      literature. METHODS: In 2007-2008 the first Hungarian survey was performed with
      the purpose to learn more about local practice of end of life decisions.
      Questionnaires were sent out electronically to 743 registered members of
      Hungarian Society of Anesthesiology and Intensive Care. Respecting anonymity, 103
      replies were statistically evaluated (response rate was 13.8%) and compared with
      data from other European countries. RESULTS: As expected, it turned out from
      replies that the practice of domestic intensive care physicians is very paternal
      and this is promoted by legal regulations that share a similar character.
      Intensive care physicians generally make their decisions alone (3.75/5 point)
      without respecting the opinion of the patient (2.57/5 point) the relatives
      (2.14/5 point) or other medical personnel (2.37/5 point). Furthermore, they
      prefer not to start a therapy rather than withdraw an ongoing treatment.
      Nevertheless, the frequency of end of life decisions (3-9% of ICU patients) is
      smaller than other European countries. CONCLUSIONS: There is a need for the
      expansion of patients' right in our country. For end of life decisions, self
      determinations must be supported and a dialogue must be established between
      lawmakers and physicians, in order to improve the legal support of this medical
      practice.

PMID- 20826378
TI  - [Blindness caused by retrobulbar hemorrhage (orbital compartment syndrome)].
AB  - In the author's department, 5 patients developed retrobulbar hemorrhage from the
      199 patients with midface fractures, between August 2007 and March 2010 (2.5%). 4
      of these patients became irreversibly blind on the affected eye. With timely
      treatment, one patient avoided blindness. The author presents a retrospective
      analysis of the patients from different departments with midface/orbital
      fractures and blindness. Bleeding and oedema behind the eyeball due to
      midface/orbital fractures in the relatively non-expandable orbit results a quick
      elevation of orbital pressure and consequently diminished circulation, ischemia,
      and later necrosis of the optic nerve (orbital compartment syndrome) with
      irreversible blindness. Immediate medical (high dose of intravenous steroids,
      mannitol, acetazolamide) and surgical intervention (lateral canthotomy,
      cantholysis, orbitotomy) on noticing the signs (proptosis, ecchymosis,
      ophthalmoplegia, mydriasis) and symptoms (pain, diplopia, decreased visual
      acuity, blindness), of a retrobulbar hemorrhage could theoretically give a chance
      to save the affected eye. Treatment started beyond 20 minutes of onset of
      blindness, might not revert the vision. Unfortunately, the description and
      treatment of the retrobulbar hemorrhage and the orbital compartment syndrome is
      not within the curriculum of the medical university, thus young colleagues could
      have vague idea about the diagnosis, the urgency and the treatment - as shown in
      these cases. With the introduction of these cases the author would like to
      highlight the signs, symptoms and necessary treatment. Knowledge of the disease
      could also increase the detected number of retrobulbar hemorrhages, which might
      be less rare than we think. Including the disease into the medical curriculum and
      postgraduate trainings could help to reduce the number of sad cases in the
      future.

PMID- 20826379
TI  - [Large deep venous thrombosis in childhood--three cases].
AB  - Deep venous thrombosis is a rare disease in children under the age of 18, with an
      estimated incidence of 1/100,000 per year in Hungary. Its typical localization in
      children is in the extremities, usually occurring in newborns and in teenagers.
      Both congenital and acquired risk factors can be in the background. Although it
      is a rarity, we should think of it, because late diagnosis can cause life
      threatening conditions like pulmonary embolism or central nervous system
      thrombosis. Detailed medical history can help the diagnosis. Etiology, possible
      congenital and acquired risk factors, as well as diagnostic and therapeutic
      options are discussed through three cases of teenage children. Diagnostic
      difficulties of deep venous thrombosis in childhood are the following: the
      occurrence is rarer than in adulthood therefore it is often forgotten as a
      possible diagnosis, coagulation parameters are age-dependent, and diagnosis with
      imaging techniques is more difficult.

PMID- 20826380
TI  - [The Spanish Flu Pandemic of 1918-1919 as reflected in the Orvosi Hetilap
      (Hungarian Medical Journal)].

PMID- 20826381
TI  - [Remembering Endre Somogyi (1922-2006)].

PMID- 20826382
TI  - ["The kidney can work miracles . . ." Interview with Laszlo Rosivall].

PMID- 20826384
TI  - Developing measurement indices to enhance protection and resilience of critical
      infrastructure and key resources.
AB  - The US Department of Homeland Security (DHS) is developing indices to better
      assist in the risk management of critical infrastructures. The first of these
      indices is the Protective Measures Index - a quantitative index that measures
      overall protection across component categories: physical security, security
      management, security force, information sharing, protective measures and
      dependencies. The Protective Measures Index, which can also be recalculated as
      the Vulnerability Index, is a way to compare differing protective measures (eg
      fence versus security training). The second of these indices is the Resilience
      Index, which assesses a site's resilience and consists of three primary
      components: robustness, resourcefulness and recovery. The third index is the
      Criticality Index, which assesses the importance of a facility. The Criticality
      Index includes economic, human, governance and mass evacuation impacts. The
      Protective Measures Index, Resilience Index and Criticality Index are being
      developed as part of the Enhanced Critical Infrastructure Protection initiative
      that DHS protective security advisers implement across the nation at critical
      facilities. This paper describes two core themes: determination of the
      vulnerability, resilience and criticality of a facility and comparison of the
      indices at different facilities.

PMID- 20826385
TI  - Business recovery at an arson damaged office.
AB  - This paper is in the form of a case study that relates how KPMG's crisis
      management, business recovery and risk mitigation plans, methods and organisation
      were applied to ensure its clients' services were not compromised following
      significant damage to a major office following an arson attack. The paper
      describes the firm's overall business continuity management (BCM) approach and
      its key principles, drawn from established BCM, emergency services and psychology
      sources. The narrative element of the article tracks the event timeline and the
      firm's corresponding response. The overall management of the incident and its
      consequences were deemed successful, validating a lean BCM training and exercise
      regime. A significant learning point was the need to manage numerous
      stakeholders' interests, engaging on several fronts in parallel, to engender
      consensus and to expedite decision making. The paper offers practical suggestions
      to help organisations manage the impact of crisis events on their employees and
      clients.

PMID- 20826386
TI  - Enhancing private sector engagement: Louisiana's business emergency operations
      centre.
AB  - Public sector emergency management is more effective when it coordinates its
      efforts with private sector companies that can provide useful capabilities
      faster, cheaper and better than government agencies. A business emergency
      operations centre (EOC) provides a space for private sector and non-governmental
      organisations to gather together in support of government efforts. This paper
      reviews business-related EOC practices in multiple US states and details the
      development of a new business EOC by the State of Louisiana, including lessons
      learned in response to the May 2010 oil spill.

PMID- 20826387
TI  - Evolving emergency programme models.
AB  - The topic of this paper is framed within the context of the evolution of what is
      referred to as modern emergency management programmes covering the 20th and 21st
      century, and is centred on two main questions: 'How does an emergency management
      programme fit within the broader construct of an organisational entity?' and
      'What changes are needed to have emergency management programmes regarded as
      strategic value-added programmes?' Why these questions should be of interest to
      emergency managers will be explored in this paper. Reference will be made to the
      evolution of the emergency programme at Toronto Pearson International Airport as
      it relates to the application of the approaches and principles discussed.

PMID- 20826388
TI  - An integrated approach to managing disruption-related risk: life and death in a
      model community.
AB  - One of the difficulties in examining organisational resilience in a community
      setting is the sheer complexity of the interrelationships essential to creating
      and sustaining that resilience. Very often, one is reduced to synthesising
      simpler hypothetical models to try to define and analyse the key aspects of
      resilience to volatility in the environment. This paper uses a university
      organisational setting as a real-life model of a community to explore the key
      arrangements essential for establishing resilience. Australia's worst recorded
      natural disaster, the devastating Victorian bushfires of February 2009, provides
      a context against which the resilience arrangements of an organisation, and by
      extrapolation a model community, can be examined.

PMID- 20826389
TI  - Principles to enable leaders to navigate the harsh realities of crisis and risk
      communication.
AB  - Leadership during a crisis that involves the physical safety and emotional or
      financial wellbeing of those being led offers an intense environment that may not
      allow for on-the-job training. One of the challenges faced by crisis leaders is
      to communicate effectively the courses of action needed to allow for a reduction
      of harm to individuals and the ultimate restoration of the group, organisation or
      community. The six principles of crisis and emergency risk communication (CERC)
      give leaders tools to navigate the harsh realities of speaking to employees,
      media, partners and stakeholders during an intense crisis. CERC also helps
      leaders to avoid the five most common communication mistakes during crises. Much
      of the harmful individual and group behaviour predicted in a profound crisis can
      be mitigated with effective crisis and emergency risk communication. A leader
      must anticipate what mental stresses followers will be experiencing and apply
      appropriate communication strategies to attempt to manage these stresses among
      staff or the public and preserve or repair the organisation's reputation. In an
      emergency, the right message at the right time is a 'resource multiplier' - it
      helps leaders to get their job done.

PMID- 20826390
TI  - How to create a public-private partnership: a replicable project associated with
      business continuity.
AB  - In an age of political turmoil and mistrust of governments, having an outlet for
      creative problem solving that involves all aspects of communities during
      disasters is critical. Additionally, there is a need for outlets that save
      taxpayer money for particular projects, such as road construction or
      infrastructure protection. Public-private partnerships are one way to accomplish
      these goals. Utilised correctly, a public-private partnership is a win-win
      situation for all participants. This paper will make the case for the continued
      support from all sectors for public-private partnerships. A description of public
      private partnerships will be given to show the broad spectrum of opportunities
      for such a partnership. In addition, a case study of a public-private partnership
      called SAFER Santa Rosa is explored as the programme is oriented towards
      disasters, but keeps the community engaged all year round. Finally, an example is
      presented of an initiative that not only exemplifies the spirit of public-private
      partnerships, but has attracted international recognition because it is simple,
      replicable, cost-effective and valuable to both the private sector and the public
      sector. The Business Emergency Response Toolkit bag is a true public-private
      success story. It is hoped that the reader will be able to replicate the ideas
      discussed herein in their own community.

PMID- 20826391
TI  - Collective response to public health emergencies and large-scale disasters:
      putting hospitals at the core of community resilience.
AB  - Healthcare organisations are a critical part of a community's resilience and play
      a prominent role as the backbone of medical response to natural and manmade
      disasters. The importance of healthcare organisations, in particular hospitals,
      to remain operational extends beyond the necessity to sustain uninterrupted
      medical services for the community, in the aftermath of a large-scale disaster.
      Hospitals are viewed as safe havens where affected individuals go for shelter,
      food, water and psychosocial assistance, as well as to obtain information about
      missing family members or learn of impending dangers related to the incident. The
      ability of hospitals to respond effectively to high-consequence incidents
      producing a massive arrival of patients that disrupt daily operations requires
      surge capacity and capability. The activation of hospital emergency support
      functions provides an approach by which hospitals manage a short-term shortfall
      of hospital personnel through the reallocation of hospital employees, thereby
      obviating the reliance on external qualified volunteers for surge capacity and
      capability. Recent revisions to the Joint Commission's hospital emergency
      preparedness standard have impelled healthcare facilities to participate actively
      in community-wide planning, rather than confining planning exclusively to a
      single healthcare facility, in order to harmonise disaster management strategies
      and effectively coordinate the allocation of community resources and expertise
      across all local response agencies.

PMID- 20826392
TI  - Local versus systemic treatment for primary cutaneous B-cell lymphoma.

PMID- 20826393
TI  - Multidisciplinary care in the management of patients with cutaneous lymphoma: a
      perspective.

PMID- 20826394
TI  - A look at the National Comprehensive Cancer Network guidelines for cutaneous
      lymphomas.

PMID- 20826395
TI  - Cutaneous Lymphoma Summit 2009.

PMID- 20826397
TI  - The state of cutaneous lymphomas: a call to action.

PMID- 20826398
TI  - Outsmarting cutaneous T-cell lymphoma cells by decoding the language they speak:
      focusing past and present insights on future prospects.

PMID- 20826399
TI  - Trends in cutaneous lymphoma epidemiology.

PMID- 20826400
TI  - Familial mycosis fungoides: model of genetic susceptibility.

PMID- 20826401
TI  - What can psoriasis teach us about the genetic basis of cutaneous T-cell lymphoma?

PMID- 20826402
TI  - Lessons learned from the systematic evaluation of cutaneous T-cell lymphomas at
      the national cancer institute and the roadmap for future studies.

PMID- 20826403
TI  - Rational clinical trial design in cutaneous lymphoma.

PMID- 20826404
TI  - New strategies to optimize outcomes in patients with T-cell lymphoma.

PMID- 20826405
TI  - The United States Cutaneous Lymphoma Consortium (USCLC).

PMID- 20826406
TI  - A cutaneous T-cell lymphoma EORTC trials platform.

PMID- 20826408
TI  - Hematopoietic stem cell transplantation for cutaneous T-cell lymphoma.

PMID- 20826407
TI  - Immune modulators as therapeutic agents for cutaneous T-cell lymphoma.

PMID- 20826409
TI  - Radiation therapy and cutaneous lymphoma.

PMID- 20826410
TI  - Unraveling the conundrum of quality.

PMID- 20826411
TI  - Improving quality in stroke rehabilitation.
AB  - Given the numerous quality improvement (QI) initiatives that have been undertaken
      in various medical fields, it is clear that inpatient rehabilitation services,
      particularly those geared toward stroke rehabilitation, can also benefit from
      these programs. To effectively evaluate the quality of rehabilitation services,
      indicators measuring structure, process, and outcomes must be included as part of
      any QI initiative. In addition to measuring quality, these indicators can be used
      to describe and address disparities in the provision of rehabilitation services
      on the basis of race, socioeconomic status, geography, disability status, and a
      multitude of other demographic factors. To improve quality and address health
      disparities associated with stroke rehabilitation, QI initiatives must be
      scientifically driven, continuing the trend of evidence-based practice in
      medicine. They must also remain flexible, because the science of quality
      improvement is an ever-changing field. It will be a challenge to convince
      physicians and other health care professionals that QI initiatives are a
      worthwhile investment of their limited time and resources, and further research
      is required to move the field of quality in stroke rehabilitation forward.

PMID- 20826412
TI  - Conceptual overview of frameworks for measuring quality in rehabilitation.
AB  - This article reviews theories and conceptual models that may be helpful in
      evaluating quality of care in rehabilitation, with a focus on the seminal
      Donabedian model of structure, process, and outcomes. In addition, this article
      reviews a variety of new theories and conceptual models that have been developed
      to expand the Donabedian model in areas specific to rehabilitation (eg, the
      multidisciplinary team, assistive technology), and it covers new approaches
      developed to help with implementing changes to improve quality. Directions for
      future research and development are identified, including the need for consensus
      and consistent use of terminology and measures and the need for quality measures
      with greater breadth, depth, and granularity that capture the complex
      interactions between the structure and processes of care unique to rehabilitation
      of physical disability.

PMID- 20826413
TI  - Risk adjustment in rehabilitation quality improvement.
AB  - Risk adjustment is an important tool for examining quality and outcomes of care.
      Considerable work has been accomplished in developing and applying risk
      adjustment to a variety of health care settings. The knowledge gained from these
      experiences is increasingly available to help guide clinicians, managers, and
      policy makers in the area of stroke rehabilitation. Key issues include
      understanding the purpose of risk adjustment, the unique population being
      examined, and the specific outcomes of interest. Risk adjustment should also be
      based on models that have good statistical properties and also make sense to
      clinicians working in the field. Risk-adjustment systems such as the FIMTM-
      function-related groups (FIM-FRGs) are now being used to monitor the quality of
      stroke rehabilitation. A specific application of this risk-adjustment system is
      demonstrated.

PMID- 20826414
TI  - Grading: an annotated "pen and paper" approach to multidimensional case-mix
      adjusted continuous quality improvement.
AB  - In this article, we present a simple multidimensional approach to case-mix
      adjustment that can be used without sophisticated statistical or computer
      programs. The objectives are to synthesize and offer examples of practical
      applications of the principles provided in the other articles in this issue of
      Topics in Stroke Rehabilitation. Combining case-mix adjustment concepts presented
      by Berlowitz and coworkers with the educate, execute, and evaluate process
      presented by Needham and coworkers, the approach applies functional grading to
      show how to evaluate the impact on patient outcomes after major changes in the
      structural characteristics of an integrated rehabilitation program within a large
      hospital-based health system. The example is based on the vignette, Maintaining
      Functional Outcomes in Times of Change, which appears in the article, "Unraveling
      the Conundrum of Quality" in this issue.

PMID- 20826415
TI  - Rehabilitation quality improvement in an intensive care unit setting:
      implementation of a quality improvement model.
AB  - OBJECTIVE: There are barriers to providing early physical medicine and
      rehabilitation (PM&R) in the intensive care unit (ICU). We present a specific
      model for undertaking quality improvement (QI) projects and a case study focused
      on QI for early PM&R in the ICU. METHODS: The QI project was undertaken using a 4
      step model: (1) summarizing the evidence, (2) identifying barriers, (3)
      establishing performance measures, and (4) ensuring patients receive the
      intervention. To evaluate the application and outcomes of this model, we present
      data collected during a 4-month QI period versus an immediately preceding 3-month
      control period. RESULTS: Deep sedation was a major barrier to early PM&R that was
      addressed in the QI project. Compared to the control period, there was a decrease
      in medical ICU (MICU) days with any benzodiazepine use (73% vs 96% of days, P =
      .03) and narcotic use (77% vs 96%, P = .05) and improved delirium status (MICU
      days without delirium, 53% vs 21%, P = .003). In addition, more QI patients had
      physical therapy consultations (93% vs 59%, P = .004) and greater number of
      rehabilitation treatments with higher functional mobility (treatments involving
      sitting or greater mobility, 78% vs 56%, P = .03). Hospital data for the QI
      period demonstrated a decrease in average length of stay in the MICU (4.9 vs 7.0
      days, P = .02) and hospital (14.1 vs 17.2, P = .03) compared to the prior year.
      CONCLUSION: A structured QI model can be applied to implementation of early PM&R
      in the ICU resulting in markedly improved delirium status, delivery of PM&R,
      functional mobility, and length of stay.

PMID- 20826416
TI  - Measuring team process for quality improvement.
AB  - BACKGROUND: Even though team care is pivotal to stroke rehabilitation, we have
      few tools to measure team process. Process measures of team functioning would
      benefit stroke rehabilitation outcomes and quality improvement (QI). OBJECTIVE:
      To improve measures of team process and evaluate their potential for use in
      rehabilitation research and QI. METHODS: We use item response theory (IRT) to
      analyze and revise selected scales from the Team Functioning Survey administrated
      to rehabilitation staff (n=365 at 31 VA hospitals) as part of a national clinical
      trial (NCT00237757). Revised scales were evaluated for reliability (Cronbach's
      alpha) and validity (correlations, predictions of patient outcomes). RESULTS:
      Eight scales (60 items) were selected from the TFS for analyses based on their
      specificity to rehabilitation and potential utility in process improvement.
      Factor analyses supported the dropping of 2 scales and the combining of 2 scales.
      As indicated by the IRT analyses of scale psychometric properties, poor
      performing scale items were dropped and item response categories modified needed
      areas for further development were identified. Cronbach's alpha for the resultant
      best 5 scales was good. Intercorrelations varied among scales but were mostly in
      the moderate ranges. Two of the scales predicted patient outcomes of mFIMTM gain
      or discharge disposition. CONCLUSION: The analyses resulted in measures of 5
      central components of team functioning: physician support, shared leadership,
      supervisor team support, teamness, and team effectiveness. IRT enables the scales
      to be refined and strengthened for use in outcome research and QI. The scales are
      proposed as another step toward understanding and enhancing team process.

PMID- 20826417
TI  - Stroke rehabilitation quality indicators: raising the bar in the inpatient
      rehabilitation facility.
AB  - Even though quality indicators are becoming more common in clinical medicine,
      there are very few of them in the area of stroke rehabilitation. This article
      proposes quality indicators for stroke rehabilitation based upon the Donabedian
      triad of structure, process, and outcomes. The quality indicators are in 3
      categories: service delivery; system care coordination; and stroke prevention,
      health promotion, and medical management. Specific areas of focus include
      organized care, intensity of service, transitions of care, secondary stroke
      prevention, hypertension, diabetes mellitus, coronary artery disease,
      hyperlipidemia, deep venous thrombosis prophylaxis, pneumonia and influenza
      vaccines, and patient and professional education. By highlighting both the
      presence and absence of evidence in various aspects of stroke rehabilitation,
      clinicians and researchers can focus on quality improvement in areas that already
      are known while providing opportunities for research into areas that evidence
      does not yet support.

PMID- 20826418
TI  - Stroke rehabilitation: the quality journey.

PMID- 20826420
TI  - The role of kinesiotaping combined with botulinum toxin to reduce plantar flexors
      spasticity after stroke.
AB  - PURPOSE: To evaluate the effect of kinesiotaping as an adjuvant therapy to
      botulinum toxin A (BTX-A) injection in lower extremity spasticity. METHODS: This
      is a single-center, randomized, and double-blind study. Twenty hemiplegic
      patients with spastic equinus foot were enrolled into the study and randomized
      into 2 groups. The first group (n=10) received BTX-A injection and kinesiotaping,
      and the second group (n=10) received BTX-A injection and sham-taping. Clinical
      assessment was done before injection and at 2 weeks and 1, 3, and 6 months.
      Outcome measures were modified Ashworth scale (MAS), passive ankle dorsiflexion,
      gait velocity, and step length. RESULTS: Improvement was recorded in both
      kinesiotaping and sham groups for all outcome variables. No significant
      difference was found between groups other than passive range of motion (ROM),
      which was found to have increased more in the kinesiotaping group at 2 weeks.
      CONCLUSION: There is no clear benefit in adjuvant kinesiotaping application with
      botulinum toxin for correction of spastic equinus in stroke.

PMID- 20826419
TI  - Patterns of relationships between background characteristics, coping, and stroke
      caregiver outcomes.
AB  - PURPOSE: Little is known about mediators of stroke caregiver outcomes or patterns
      of relationships of outcome predictors. We examined relationships between the
      variable sets of caregiver and stroke survivor characteristics, coping (proposed
      mediators), and caregiver outcomes. METHODS: We assessed 253 dyads prior to
      discharge from acute rehabilitation. Outcomes were depression, anxiety,
      preparedness, life change, and family functioning. Coping included problem
      solving, caregiver appraisal, and unmet resource needs. Multivariate canonical
      correlation analyses were computed between the sets of variables to identify
      unique patterns of relationships. RESULTS: Six patterns of significant
      relationships were found (R =.30 to .84, Ps <.01 to .02). The strongest
      relationship was that between greater threat appraisal and negative life change,
      greater anxiety, and lower caregiving preparedness (P < .01). Caregiver
      characteristics (nonwhite, spousal caregivers) were related significantly to
      several outcomes (positive life change, lower anxiety, and less healthy family
      functioning) (R = .43, P <.01) and remained significant after controlling for the
      effect of mediators (R = .32, P < .02). CONCLUSION: Findings suggest various
      patterns of relationships that provide guidance for individualizing early
      caregiver intervention. Clinicians can build on caregivers' strengths while
      identifying threats to adaptation to tailor interventions that promote healthy
      outcomes.

PMID- 20826421
TI  - Effects of auditory feedback on movement time in a Fitts task.
AB  - The purpose of the present experiment was to investigate the role of auditory
      feedback and its impact on movement time in a standard Fitts task. Feedback was
      given at the moment of target acquisition. A 2-way analysis of variance found
      significant differences between feedback groups at all three indexes of
      difficulty (F(2, 40) = 156.02, p < .001). Results from a mixed-model multivariate
      analysis of variance for kinematic factors show significant differences in peak
      velocity and the location of peak velocity when comparing feedback groups. In
      general, the addition of auditory feedback decreased the task ID by .5.

PMID- 20826422
TI  - Motor learning through induced variability at the task goal and execution
      redundancy levels.
AB  - The authors examined the influence of introducing variability at two different
      levels in the learning of a striking task. Variability at the task goal level was
      introduced by changing target location, whereas variability at the execution
      redundancy level was introduced by using an intermediate target that constrained
      participants to use different paths from trial to trial to strike the same
      target. After practice, participants were transferred to 2 test conditions: (a) a
      fixed-target test, where the position of the target was unchanged; and (b) a
      variable-target test, where the position of the target was varied from trial to
      trial. The results from the manipulation at the task goal level were consistent
      with predictions from the specificity of practice hypothesis. In both the fixed-
      and variable-target tests, the best performance was achieved by the group that
      had practiced in the condition matching the test condition. At the execution
      redundancy level, practicing multiple solutions to achieve the task goal did not
      improve performance in either the fixed- or variable-target tests. These results
      show that introducing variability at the task goal and execution redundancy
      levels has different effects on learning and generalization and that practice
      schedules that constrain the participant to use redundant solutions may not
      facilitate learning.

PMID- 20826423
TI  - Offline improvement during motor sequence learning is not restricted to
      developing motor chunks.
AB  - Robust offline performance gains, beyond those that would be anticipated by being
      exposed to additional physical practice, have been reported during procedural
      learning and have been attributed to enhancement consolidation, a process by
      which memory is transformed in such a way that it is not only more resistant to
      forgetting but may also involve a reorganization of information that supports
      superior task execution. The authors assessed the impact of increasing within
      session practice extent on the emergence of offline performance gains. Practice
      dependent improvements occurred across 12 and 24 30-s practice trials of a 5
      element motor sequencing task. Offline improvements were observed following both
      12 and 24 trials. The improvement following 12 trials was associated with the
      formation of motor chunks important for establishing movement sequence structure.
      In contrast, the offline improvement after 24 trials was not related to further
      changes in movement structure beyond those that had emerged during practice.
      These data suggest that additional memory operations, beyond those needed to
      amalgamate subsequences of the SRT task, are susceptible to enhancement
      consolidation.

PMID- 20826424
TI  - Sequential aiming with two limbs and the one-target advantage.
AB  - Movement times to the first target in a 2-target sequence are typically slower
      than in 1-target aiming tasks. The 1-target movement time advantage has been
      shown to emerge regardless of hand preference, the hand used, the amount of
      practice, and the availability of visual feedback. The authors tested central and
      peripheral explanations of the 1-target advantage, as postulated by the movement
      integration hypothesis, by asking participants to perform single-target
      movements, 2-target movements with 1 limb, and 2-target movements in which they
      switched limbs at the first target. Reaction time and movement time data showed a
      1-target advantage that was similar for both 1- and 2-limb sequential aiming
      movements. This outcome demonstrates that the processes underlying the increase
      in movement time to the 1st target in 2-target sequences are not specific to the
      limb, suggesting that the 1-target advantage originates at a central rather than
      a peripheral level.

PMID- 20826425
TI  - Targeting of the orphan receptor GPR35 by pamoic acid: a potent activator of
      extracellular signal-regulated kinase and beta-arrestin2 with antinociceptive
      activity.
AB  - Known agonists of the orphan receptor GPR35 are kynurenic acid, zaprinast, 5
      nitro-2-(3-phenylproplyamino) benzoic acid, and lysophosphatidic acids. Their
      relatively low affinities for GPR35 and prominent off-target effects at other
      pathways, however, diminish their utility for understanding GPR35 signaling and
      for identifying potential therapeutic uses of GPR35. In a screen of the Prestwick
      Library of drugs and drug-like compounds, we have found that pamoic acid is a
      potent GPR35 agonist. Pamoic acid is considered by the Food and Drug
      Administration as an inactive compound that enables long-acting formulations of
      numerous drugs, such as the antihelminthics oxantel pamoate and pyrantel pamoate;
      the psychoactive compounds hydroxyzine pamoate (Vistaril) and imipramine pamoate
      (Tofranil-PM); and the peptide hormones triptorelin pamoate (Trelstar) and
      octreotide pamoate (OncoLar). We have found that pamoic acid induces a G(i/o)
      linked, GPR35-mediated increase in the phosphorylation of extracellular signal
      regulated kinase 1/2, recruitment of beta-arrestin2 to GPR35, and internalization
      of GPR35. In mice, it attenuates visceral pain perception, indicating an
      antinociceptive effect, possibly through GPR35 receptors. We have also identified
      in collaboration with the Sanford-Burnham Institute Molecular Libraries Probe
      Production Center new classes of GPR35 antagonist compounds, including the
      nanomolar potency antagonist methyl-5-[(tert
      butylcarbamothioylhydrazinylidene)methyl]-1-(2,4-difluorophenyl)pyrazole-4
      carboxylate (CID2745687). Pamoic acid and potent antagonists such as CID2745687
      present novel opportunities for expanding the chemical space of GPR35,
      elucidating GPR35 pharmacology, and stimulating GPR35-associated drug
      development. Our results indicate that the unexpected biological functions of
      pamoic acid may yield potential new uses for a common drug constituent.

PMID- 20826426
TI  - Brain. Editorial.

PMID- 20826427
TI  - Beneficial brain autoimmunity?

PMID- 20826428
TI  - Early and late talkers: school-age language, literacy and neurolinguistic
      differences.
AB  - Early language development sets the stage for a lifetime of competence in
      language and literacy. However, the neural mechanisms associated with the
      relative advantages of early communication success, or the disadvantages of
      having delayed language development, are not well explored. In this study, 174
      elementary school-age children whose parents reported that they started forming
      sentences 'early', 'on-time' or 'late' were evaluated with standardized measures
      of language, reading and spelling. All oral and written language measures
      revealed consistent patterns for 'early' talkers to have the highest level of
      performance and 'late' talkers to have the lowest level of performance. We report
      functional magnetic resonance imaging data from a subset of early, on-time and
      late talkers matched for age, gender and performance intelligence quotient that
      allows evaluation of neural activation patterns produced while listening to and
      reading real words and pronounceable non-words. Activation in bilateral thalamus
      and putamen, and left insula and superior temporal gyrus during these tasks was
      significantly lower in late talkers, demonstrating that residual effects of being
      a late talker are found not only in behavioural tests of oral and written
      language, but also in distributed cortical-subcortical neural circuits underlying
      speech and print processing. Moreover, these findings suggest that the age of
      functional language acquisition can have long-reaching effects on reading and
      language behaviour, and on the corresponding neurocircuitry that supports
      linguistic function into the school-age years.

PMID- 20826429
TI  - Education, the brain and dementia: neuroprotection or compensation?
AB  - The potential protective role of education for dementia is an area of major
      interest. Almost all older people have some pathology in their brain at death but
      have not necessarily died with dementia. We have explored these two observations
      in large population-based cohort studies (Epidemiological Clinicopathological
      Studies in Europe; EClipSE) in an investigation of the relationships of brain
      pathology at death, clinical dementia and time in education, testing the
      hypothesis that greater exposure to education reduces the risk of dementia.
      EClipSE has harmonized longitudinal clinical data and neuropathology from three
      longstanding population-based studies that included post-mortem brain donation.
      These three studies started between 1985 and 1991. Number of years of education
      during earlier life was recorded at baseline. Incident dementia was detected
      through follow-up interviews, complemented by retrospective informant interviews,
      death certificate data and linked health/social records (dependent on study)
      after death. Dementia-related neuropathologies were assessed in each study in a
      comparable manner based on the Consortium to Establish a Registry for Alzheimer's
      Disease protocol. Eight hundred and seventy-two brain donors were included, of
      whom 56% were demented at death. Longer years in education were associated with
      decreased dementia risk and greater brain weight but had no relationship to
      neurodegenerative or vascular pathologies. The associations between
      neuropathological variables and clinical dementia differed according to the
      'dose' of education such that more education reduced dementia risk largely
      independently of severity of pathology. More education did not protect
      individuals from developing neurodegenerative and vascular neuropathology by the
      time they died but it did appear to mitigate the impact of pathology on the
      clinical expression of dementia before death. The findings suggest that an
      understanding of the mechanisms leading to functional protection in the presence
      of pathology may be of considerable value to society.

PMID- 20826430
TI  - Functional role of brain-derived neurotrophic factor in neuroprotective
      autoimmunity: therapeutic implications in a model of multiple sclerosis.
AB  - Brain-derived neurotrophic factor plays a key role in neuronal and axonal
      survival. Brain-derived neurotrophic factor is expressed in the immune cells in
      lesions of experimental autoimmune encephalomyelitis and multiple sclerosis, thus
      potentially mediating neuroprotective effects. We investigated the functional
      role of brain-derived neurotrophic factor in myelin oligodendrocyte glycoprotein
      induced experimental autoimmune encephalomyelitis, an animal model of multiple
      sclerosis. Mice deficient for brain-derived neurotrophic factor in immune cells
      displayed an attenuated immune response in the acute phase of experimental
      autoimmune encephalomyelitis, but progressive disability with enhanced axonal
      loss in the chronic phase of the disease. In mice deficient for central nervous
      system-derived brain-derived neurotrophic factor via glial fibrillary acidic
      protein-crescentin-mediated deletion, a more severe course of experimental
      autoimmune encephalomyelitis and an overall increased axonal loss was observed.
      In a lentiviral approach, injection of brain-derived neurotrophic factor
      overexpressing T cells led to a less severe course of experimental autoimmune
      encephalomyelitis and direct axonal protection. Our data imply a functional role
      of brain-derived neurotrophic factor in autoimmune demyelination by mediating
      axon protection.

PMID- 20826431
TI  - Global gene expression profiling of somatic motor neuron populations with
      different vulnerability identify molecules and pathways of degeneration and
      protection.
AB  - Different somatic motor neuron subpopulations show a differential vulnerability
      to degeneration in diseases such as amyotrophic lateral sclerosis, spinal
      muscular atrophy and spinobulbar muscular atrophy. Studies in mutant superoxide
      dismutase 1 over-expressing amyotrophic lateral sclerosis model mice indicate
      that initiation of disease is intrinsic to motor neurons, while progression is
      promoted by astrocytes and microglia. Therefore, analysis of the normal
      transcriptional profile of motor neurons displaying differential vulnerability to
      degeneration in motor neuron disease could give important clues to the mechanisms
      of relative vulnerability. Global gene expression profiling of motor neurons
      isolated by laser capture microdissection from three anatomical nuclei of the
      normal rat, oculomotor/trochlear (cranial nerve 3/4), hypoglossal (cranial nerve
      12) and lateral motor column of the cervical spinal cord, displaying differential
      vulnerability to degeneration in motor neuron disorders, identified enriched
      transcripts for each neuronal subpopulation. There were striking differences in
      the regulation of genes involved in endoplasmatic reticulum and mitochondrial
      function, ubiquitination, apoptosis regulation, nitrogen metabolism, calcium
      regulation, transport, growth and RNA processing; cellular pathways that have
      been implicated in motor neuron diseases. Confirmation of genes of immediate
      biological interest identified differential localization of insulin-like growth
      factor II, guanine deaminase, peripherin, early growth response 1, soluble
      guanylate cyclase 1A3 and placental growth factor protein. Furthermore, the
      cranial nerve 3/4-restricted genes insulin-like growth factor II and guanine
      deaminase protected spinal motor neurons from glutamate-induced toxicity (P <
      0.001, ANOVA), indicating that our approach can identify factors that protect or
      make neurons more susceptible to degeneration.

PMID- 20826432
TI  - The structural plasticity of white matter networks following anterior temporal
      lobe resection.
AB  - Anterior temporal lobe resection is an effective treatment for refractory
      temporal lobe epilepsy. The structural consequences of such surgery in the white
      matter, and how these relate to language function after surgery remain unknown.
      We carried out a longitudinal study with diffusion tensor imaging in 26 left and
      20 right temporal lobe epilepsy patients before and a mean of 4.5 months after
      anterior temporal lobe resection. The whole-brain analysis technique tract-based
      spatial statistics was used to compare pre- and postoperative data in the left
      and right temporal lobe epilepsy groups separately. We observed widespread,
      significant, mean 7%, decreases in fractional anisotropy in white matter networks
      connected to the area of resection, following both left and right temporal lobe
      resections. However, we also observed a widespread, mean 8%, increase in
      fractional anisotropy after left anterior temporal lobe resection in the
      ipsilateral external capsule and posterior limb of the internal capsule, and
      corona radiata. These findings were confirmed on analysis of the native clusters
      and hand drawn regions of interest. Postoperative tractography seeded from this
      area suggests that this cluster is part of the ventro-medial language network.
      The mean pre- and postoperative fractional anisotropy and parallel diffusivity in
      this cluster were significantly correlated with postoperative verbal fluency and
      naming test scores. In addition, the percentage change in parallel diffusivity in
      this cluster was correlated with the percentage change in verbal fluency after
      anterior temporal lobe resection, such that the bigger the increase in parallel
      diffusivity, the smaller the fall in language proficiency after surgery. We
      suggest that the findings of increased fractional anisotropy in this ventro
      medial language network represent structural reorganization in response to the
      anterior temporal lobe resection, which may damage the more susceptible dorso
      lateral language pathway. These findings have important implications for our
      understanding of brain injury and rehabilitation, and may also prove useful in
      the prediction and minimization of postoperative language deficits.

PMID- 20826433
TI  - Reorganization of functional connectivity as a correlate of cognitive recovery in
      acquired brain injury.
AB  - Cognitive processes require a functional interaction between specialized
      multiple, local and remote brain regions. Although these interactions can be
      strongly altered by an acquired brain injury, brain plasticity allows network
      reorganization to be principally responsible for recovery. The present work
      evaluates the impact of brain injury on functional connectivity patterns.
      Networks were calculated from resting-state magnetoencephalographic recordings
      from 15 brain injured patients and 14 healthy controls by means of wavelet
      coherence in standard frequency bands. We compared the parameters defining the
      network, such as number and strength of interactions as well as their topology,
      in controls and patients for two conditions: following a traumatic brain injury
      and after a rehabilitation treatment. A loss of delta- and theta-based
      connectivity and conversely an increase in alpha- and beta-band-based
      connectivity were found. Furthermore, connectivity parameters approached controls
      in all frequency bands, especially in slow-wave bands. A correlation between
      network reorganization and cognitive recovery was found: the reduction of delta
      band-based connections and the increment of those based on alpha band correlated
      with Verbal Fluency scores, as well as Perceptual Organization and Working Memory
      Indexes, respectively. Additionally, changes in connectivity values based on
      theta and beta bands correlated with the Patient Competency Rating Scale. The
      current study provides new evidence of the neurophysiological mechanisms
      underlying neuronal plasticity processes after brain injury, and suggests that
      these changes are related with observed changes at the behavioural level.

PMID- 20826434
TI  - Magnetic resonance imaging lesion pattern in Guadeloupean parkinsonism is
      distinct from progressive supranuclear palsy.
AB  - In the Caribbean island of Guadeloupe, patients with atypical parkinsonism
      develop a progressive supranuclear palsy-like syndrome, named Guadeloupean
      parkinsonism. Unlike the classical forms of progressive supranuclear palsy, they
      develop hallucinations and myoclonus. As lesions associated with Guadeloupean
      parkinsonism are poorly characterized, it is not known to what extent they differ
      from progressive supranuclear palsy. The aim of the present study was to
      determine the structural and metabolic profiles of Guadeloupean parkinsonism
      compared with progressive supranuclear palsy and controls using combined
      structural and diffusion magnetic resonance imaging and magnetic resonance
      spectroscopy. We included 9 patients with Guadeloupean parkinsonism, 10 with
      progressive supranuclear palsy and 9 age-matched controls. Magnetic resonance
      imaging examination was performed at 1.5 T and included 3D T(1)-weighted and
      fluid-attenuated inversion recovery images, diffusion tensor imaging and single
      voxel magnetic resonance spectroscopy in the lenticular nucleus. Images were
      analysed using voxel-based morphometry, voxel-based diffusion tensor imaging and
      brainstem region of interest measurements. In patients with Guadeloupean
      parkinsonism, structural and diffusion changes predominated in the temporal and
      occipital lobes, the limbic areas (medial temporal, orbitofrontal and cingulate
      cortices) and the cerebellum. In contrast to patients with progressive
      supranuclear palsy, structural changes predominated in the midbrain and the basal
      ganglia and diffusion abnormalities predominated in the frontocentral white
      matter, the basal ganglia and the brainstem. Compared with controls, the N
      acetylaspartate to creatinine ratio was decreased in patients with progressive
      supranuclear palsy and to a lesser extent in patients with Guadeloupean
      parkinsonism. The pattern of structural and diffusion abnormalities differed
      between progressive supranuclear palsy and Guadeloupean parkinsonism. Widespread
      cortical atrophy was observed in patients with Guadeloupean parkinsonism who
      presented marked cognitive changes and hallucinations, whereas midbrain lesions
      were less severe than in progressive supranuclear palsy. Midbrain (progressive
      supranuclear palsy) or cortical (Guadeloupean parkinsonism) atrophy was a
      distinctive neuroimaging feature for differential diagnosis.

PMID- 20826435
TI  - Rundataxin, a novel protein with RUN and diacylglycerol binding domains, is
      mutant in a new recessive ataxia.
AB  - We have identified a novel form of recessive ataxia that segregates in three
      children of a large consanguineous Saudi Arabian family. The three patients
      presented with childhood onset gait and limb ataxia, dysarthria and had limited
      walking without aid into their teenage years. Two patients developed epilepsy at
      7 months without relapse after treatment, and mental retardation. Linkage studies
      allowed us to identify a single locus that segregated with the disease on
      chromosome 3q28-qter. Mutation screening of all coding sequences revealed a
      single nucleotide deletion, 2927delC, in exon 19 of the KIAA0226 gene, which
      results in a frame shift of the C-terminal domain (p.Ala943ValfsX146). The
      KIAA0226 gene encodes a protein that we named rundataxin, with two conserved
      domains: an N-terminal RUN domain and a C-terminal domain containing a
      diacylglycerol binding-like motif. The closest paralogue of rundataxin, the
      plekstrin homology domain family member M1, has been shown to colocalize with
      Rab7, a small GTPase associated with late endosomes/lysosomes, suggesting that
      rundataxin may also be associated with vesicular trafficking and signalling
      pathways through its RUN and diacylglycerol binding-like domains. The rundataxin
      pathway appears therefore distinct from the ataxia pathways involving deficiency
      in mitochondrial or nuclear proteins and broadens the range of mechanisms leading
      to recessive ataxias.

PMID- 20826436
TI  - A mouse model for eukaryotic translation initiation factor 2B-leucodystrophy
      reveals abnormal development of brain white matter.
AB  - Eukaryotic translation initiation factor 2B is a major housekeeping complex that
      governs the rate of global protein synthesis under normal and stress conditions.
      Mutations in any of its five subunits lead to leucoencephalopathy with vanishing
      white matter, an inherited chronic-progressive fatal brain disease with unknown
      aetiology, which is among the most prevalent childhood white matter disorders. We
      generated the first animal model for the disease by introducing a point mutation
      into the mouse Eif2b5 gene locus, leading to R132H replacement corresponding to
      the clinically significant human R136H mutation in the catalytic subunit. In
      contrast to human patients, mice homozygous for the mutant Eif2b5 allele
      (Eif2b5(R132H/R132H) mice) enable multiple analyses under a defined genetic
      background during the pre-symptomatic stages and during recovery from a defined
      brain insult. Time-course magnetic resonance imaging revealed for the first time
      the delayed development of the brain white matter due to the mutation. Electron
      microscopy demonstrated a higher proportion of small-calibre nerve fibres.
      Immunohistochemistry detected an abnormal abundance of oligodendrocytes and
      astrocytes in the brain of younger animals, as well as an abnormal level of major
      myelin proteins. Most importantly, mutant mice failed to recover from cuprizone
      induced demyelination, reflecting an increased sensitivity to brain insults. The
      anomalous development of white matter in Eif2b5(R132H/R132H) mice underscores the
      importance of tight translational control to normal myelin formation and
      maintenance.

PMID- 20826438
TI  - Invasion strategies in clonal aquatic plants: are phenotypic differences caused
      by phenotypic plasticity or local adaptation?
AB  - BACKGROUND AND AIMS: The successful spread of invasive plants in new environments
      is often linked to multiple introductions and a diverse gene pool that
      facilitates local adaptation to variable environmental conditions. For clonal
      plants, however, phenotypic plasticity may be equally important. Here the primary
      adaptive strategy in three non-native, clonally reproducing macrophytes (Egeria
      densa, Elodea canadensis and Lagarosiphon major) in New Zealand freshwaters were
      examined and an attempt was made to link observed differences in plant morphology
      to local variation in habitat conditions. METHODS: Field populations with a large
      phenotypic variety were sampled in a range of lakes and streams with different
      chemical and physical properties. The phenotypic plasticity of the species before
      and after cultivation was studied in a common garden growth experiment, and the
      genetic diversity of these same populations was also quantified. KEY RESULTS: For
      all three species, greater variation in plant characteristics was found before
      they were grown in standardized conditions. Moreover, field populations displayed
      remarkably little genetic variation and there was little interaction between
      habitat conditions and plant morphological characteristics. CONCLUSIONS: The
      results indicate that at the current stage of spread into New Zealand, the
      primary adaptive strategy of these three invasive macrophytes is phenotypic
      plasticity. However, while limited, the possibility that genetic diversity
      between populations may facilitate ecotypic differentiation in the future cannot
      be excluded. These results thus indicate that invasive clonal aquatic plants
      adapt to new introduced areas by phenotypic plasticity. Inorganic carbon,
      nitrogen and phosphorous were important in controlling plant size of E.
      canadensis and L. major, but no other relationships between plant characteristics
      and habitat conditions were apparent. This implies that within-species
      differences in plant size can be explained by local nutrient conditions. All
      together this strongly suggests that invasive clonal aquatic plants adapt to a
      wide range of habitats in introduced areas by phenotypic plasticity rather than
      local adaptation.

PMID- 20826437
TI  - SH3TC2, a protein mutant in Charcot-Marie-Tooth neuropathy, links peripheral
      nerve myelination to endosomal recycling.
AB  - Patients with Charcot-Marie-Tooth neuropathy and gene targeting in mice revealed
      an essential role for the SH3TC2 gene in peripheral nerve myelination. SH3TC2
      expression is restricted to Schwann cells in the peripheral nervous system, and
      the gene product, SH3TC2, localizes to the perinuclear recycling compartment.
      Here, we show that SH3TC2 interacts with the small guanosine triphosphatase
      Rab11, which is known to regulate the recycling of internalized membranes and
      receptors back to the cell surface. Results of protein binding studies and
      transferrin receptor trafficking are in line with a role of SH3TC2 as a Rab11
      effector molecule. Consistent with a function of Rab11 in Schwann cell
      myelination, SH3TC2 mutations that cause neuropathy disrupt the SH3TC2/Rab11
      interaction, and forced expression of dominant negative Rab11 strongly impairs
      myelin formation in vitro. Our data indicate that the SH3TC2/Rab11 interaction is
      relevant for peripheral nerve pathophysiology and place endosomal recycling on
      the list of cellular mechanisms involved in Schwann cell myelination.

PMID- 20826439
TI  - A functional-structural modelling approach to autoregulation of nodulation.
AB  - BACKGROUND AND AIMS: Autoregulation of nodulation is a long-distance shoot-root
      signalling regulatory system that regulates nodule meristem proliferation in
      legume plants. However, due to the intricacy and subtleness of the signalling
      nature in plants, molecular and biochemical details underlying mechanisms of
      autoregulation of nodulation remain largely unknown. The purpose of this study is
      to use functional-structural plant modelling to investigate the complexity of
      this signalling system. There are two major challenges to be met: modelling the
      3D architecture of legume roots with nodulation and co-ordinating signalling
      developmental processes with various rates. METHODS: Soybean (Glycine max) was
      chosen as the target legume. Its root system was observed to capture lateral root
      branching and nodule distribution patterns. L-studio, a software tool supporting
      context-sensitive L-system modelling, was used for the construction of the
      architectural model and integration with the internal signalling. KEY RESULTS: A
      branching pattern with regular radial angles was found between soybean lateral
      roots, from which a root mapping method was developed to characterize the
      laterals. Nodules were mapped based on 'nodulation section' to reveal nodule
      distribution. A root elongation algorithm was then developed for simulation of
      root development. Based on the use of standard sub-modules, a synchronization
      algorithm was developed to co-ordinate multi-rate signalling and developmental
      processes. CONCLUSIONS: The modelling methods developed here not only allow
      recreation of legume root architecture with lateral branching and nodulation
      details, but also enable parameterization of internal signalling to produce
      different regulation results. This provides the basis for using virtual
      experiments to help in investigating the signalling mechanisms at work.

PMID- 20826440
TI  - Role of symmetric and asymmetric division of stem cells in developing drug
      resistance.
AB  - Often, resistance to drugs is an obstacle to a successful treatment of cancer. In
      spite of the importance of the problem, the actual mechanisms that control the
      evolution of drug resistance are not fully understood. Many attempts to study
      drug resistance have been made in the mathematical modeling literature. Clearly,
      in order to understand drug resistance, it is imperative to have a good model of
      the underlying dynamics of cancer cells. One of the main ingredients that has
      been recently introduced into the rapidly growing pool of mathematical cancer
      models is stem cells. Surprisingly, this all-so-important subset of cells has not
      been fully integrated into existing mathematical models of drug resistance. In
      this work we incorporate the various possible ways in which a stem cell may
      divide into the study of drug resistance. We derive a previously undescribed
      estimate of the probability of developing drug resistance by the time a tumor is
      detected and calculate the expected number of resistant cancer stem cells at the
      time of tumor detection. To demonstrate the significance of this approach, we
      combine our previously undescribed mathematical estimates with clinical data that
      are taken from a recent six-year follow-up of patients receiving imatinib for the
      first-line treatment of chronic myelogenous leukemia. Based on our analysis we
      conclude that leukemia stem cells must tend to renew symmetrically as opposed to
      their healthy counterparts that predominantly divide asymmetrically.

PMID- 20826441
TI  - Stochastic models for large interacting systems and related correlation
      inequalities.
AB  - A very large and active part of probability theory is concerned with the
      formulation and analysis of models for the evolution of large systems arising in
      the sciences, including physics and biology. These models have in their
      description randomness in the evolution rules, and interactions among various
      parts of the system. This article describes some of the main models in this area,
      as well as some of the major results about their behavior that have been obtained
      during the past 40 years. An important technique in this area, as well as in
      related parts of physics, is the use of correlation inequalities. These express
      positive or negative dependence between random quantities related to the model.
      In some types of models, the underlying dependence is positive, whereas in others
      it is negative. We give particular attention to these issues, and to applications
      of these inequalities. Among the applications are central limit theorems that
      give convergence to a Gaussian distribution.

PMID- 20826442
TI  - Protein-induced photophysical changes to the amyloid indicator dye thioflavin T.
AB  - The small molecule thioflavin T (ThT) is a defining probe for the identification
      and mechanistic study of amyloid fiber formation. As such, ThT is fundamental to
      investigations of serious diseases such as Alzheimer's disease, Parkinson
      disease, and type II diabetes. For each disease, a different protein undergoes
      conformational conversion to a beta-sheet rich fiber. The fluorescence of ThT
      exhibits an increase in quantum yield upon binding these fibers. Despite its
      widespread use, the structural basis for binding specificity and for the changes
      to the photophysical properties of ThT remain poorly understood. Here, we report
      the co-crystal structures of ThT with two alternative states of beta-2
      microglobulin (beta2m); one monomeric, the other an amyloid-like oligomer. In the
      latter, the dye intercalates between beta-sheets orthogonal to the beta-strands.
      Importantly, the fluorophore is bound in such a manner that a photophysically
      relevant torsion is limited to a range of angles generally associated with low,
      not high, quantum yield. Quantum mechanical assessment of the fluorophore shows
      the electronic distribution to be strongly stabilized by aromatic interactions
      with the protein. Monomeric beta2m gives little increase in ThT fluorescence
      despite showing three fluorophores, at two binding sites, in configurations
      generally associated with high quantum yield. Our efforts fundamentally extend
      existing understanding about the origins of amyloid-induced photophysical
      changes. Specifically, the beta-sheet interface that characterizes amyloid acts
      both sterically and electronically to stabilize the fluorophore's ground state
      electronic distribution. By preventing the fluorophore from adopting its
      preferred excited state configuration, nonradiative relaxation pathways are
      minimized and quantum yield is increased.

PMID- 20826443
TI  - A heterodimeric complex of the LRR proteins LRIM1 and APL1C regulates complement
      like immunity in Anopheles gambiae.
AB  - The leucine-rich repeat (LRR) proteins LRIM1 and APL1C control the function of
      the complement-like protein TEP1 in Anopheles mosquitoes. The molecular structure
      of LRIM1 and APL1C and the basis of their interaction with TEP1 represent a new
      type of innate immune complex. The LRIM1/APL1C complex specifically binds and
      solubilizes a cleaved form of TEP1 without an intact thioester bond. The LRIM1
      and APL1C LRR domains have a large radius of curvature, glycosylated concave
      face, and a novel C-terminal capping motif. The LRIM1/APL1C complex is a
      heterodimer with a single intermolecular disulfide bond. The structure of the
      LRIM1/APL1C heterodimer reveals an interface between the two LRR domains and an
      extensive C-terminal coiled-coil domain. We propose that a cleaved form of TEP1
      may act as a convertase for activation of other TEP1 molecules and that the
      LRIM1/APL1C heterodimer regulates formation of this TEP1 convertase.

PMID- 20826444
TI  - Vertebrate fatty acyl desaturase with Delta4 activity.
AB  - Biosynthesis of the highly biologically active long-chain polyunsaturated fatty
      acids, arachidonic (ARA), eicosapentaenoic (EPA), and docosahexaenoic (DHA)
      acids, in vertebrates requires the introduction of up to three double bonds
      catalyzed by fatty acyl desaturases (Fad). Synthesis of ARA is achieved by Delta6
      desaturation of 182n - 6 to produce 183n - 6 that is elongated to 203n - 6
      followed by Delta5 desaturation. Synthesis of EPA from 183n - 3 requires the same
      enzymes and pathway as for ARA, but DHA synthesis reportedly requires two further
      elongations, a second Delta6 desaturation and a peroxisomal chain shortening
      step. This paper describes cDNAs, fad1 and fad2, isolated from the herbivorous,
      marine teleost fish (Siganus canaliculatus) with high similarity to mammalian Fad
      proteins. Functional characterization of the cDNAs by heterologous expression in
      the yeast Saccharomyces cerevisiae showed that Fad1 was a bifunctional
      Delta6/Delta5 Fad. Previously, functional dual specificity in vertebrates had
      been demonstrated for a zebrafish Danio rerio Fad and baboon Fad, so the present
      report suggests bifunctionality may be more widespread in vertebrates. However,
      Fad2 conferred on the yeast the ability to convert 225n - 3 to DHA indicating
      that this S. canaliculatus gene encoded an enzyme having Delta4 Fad activity.
      This is a unique report of a Fad with Delta4 activity in any vertebrate species
      and indicates that there are two possible mechanisms for DHA biosynthesis, a
      direct route involving elongation of EPA to 225n - 3 followed by Delta4
      desaturation, as well as the more complicated pathway as described above.

PMID- 20826445
TI  - Identification of the biosynthetic gene cluster for the pacidamycin group of
      peptidyl nucleoside antibiotics.
AB  - Pacidamycins are a family of uridyl tetra/pentapeptide antibiotics that act on
      the translocase MraY to block bacterial cell wall assembly. To elucidate the
      biosynthetic logic of pacidamcyins, a putative gene cluster was identified by 454
      shotgun genome sequencing of the producer Streptomyces coeruleorubidus NRRL
      18370. The 31-kb gene cluster encodes 22 proteins (PacA-V), including highly
      dissociated nonribosomal peptide synthetase (NRPS) modules and a variety of
      tailoring enzymes. Gene deletions confirmed that two NRPSs, PacP and PacO, are
      required for the biosynthesis of pacidamycins. Heterologous expression and in
      vitro assays of PacL, PacO, and PacP established reversible formation of m-Tyr
      AMP, l-Ala-AMP, and diaminopropionyl-AMP, respectively, consistent with the amino
      acids found in pacidamycin scaffolds. The unusual Ala(4)-Phe(5) dipeptidyl ureido
      linkage was formed during in vitro assays containing purified PacL, PacJ, PacN,
      and PacO. Both the genetic and enzymatic studies validate identification of the
      biosynthetic genes for this subclass of uridyl peptide antibiotics and provide
      the basis for future mechanistic study of their biosynthesis.

PMID- 20826446
TI  - Epithelial crosstalk at the microbiota-mucosal interface.
AB  - This article provides an overview of how intestinal epithelial cells (IEC)
      recognize commensals and how they maintain host-bacterial symbiosis. Endocrine,
      goblet cells, and enterocytes of the intestinal epithelium express a range of
      pattern recognition receptors (PRR) to sense the presence of microbes. The best
      characterized are the Toll-like receptors (TLR) and nucleotide oligomerization
      domain-like receptors (NLR), which play a key role in pathogen recognition and
      the induction of innate effectors and inflammation. Several adaptations of PRR
      signaling have evolved in the gut to avoid uncontrolled and potentially
      destructive inflammatory responses toward the resident microbiota. PRR signaling
      in IEC serve to maintain the barrier functions of the epithelium, including the
      production of secretory IgA (sIgA). Additionally, IECs play a cardinal role in
      setting the immunosuppressive tone of the mucosa to inhibit overreaction against
      innocuous luminal antigens. This includes regulation of dendritic cells (DC),
      macrophage and lymphocyte functions by epithelial secreted cytokines. These
      immune mechanisms depend heavily on IEC recognition of microbes and are
      consistent with several studies in knockout mice that demonstrate TLR signaling
      in the epithelium has a profoundly beneficial role in maintaining homeostasis.

PMID- 20826447
TI  - Expression and lysosomal targeting of CLN7, a major facilitator superfamily
      transporter associated with variant late-infantile neuronal ceroid
      lipofuscinosis.
AB  - Neuronal ceroid lipofuscinoses (NCLs) constitute a group of progressive
      neurodegenerative disorders resulting from mutations in at least eight different
      genes. Mutations in the most recently identified NCL gene, MFSD8/CLN7, underlie a
      variant of late-infantile NCL (vLINCL). The MFSD8/CLN7 gene encodes a polytopic
      protein with unknown function, which shares homology with ion-coupled membrane
      transporters. In this study, we confirmed the lysosomal localization of the
      native CLN7 protein. This localization of CLN7 is not impaired by the presence of
      pathogenic missense mutations or after genetic ablation of the N-glycans.
      Expression of chimeric and full-length constructs showed that lysosomal targeting
      of CLN7 is mainly determined by an N-terminal dileucine motif, which specifically
      binds to the heterotetrameric adaptor AP-1 in vitro. We also show that CLN7 mRNA
      is more abundant in neurons than astrocytes and microglia, and that it is
      expressed throughout rat brain, with increased levels in the granular layer of
      cerebellum and hippocampal pyramidal cells. Interestingly, this cellular and
      regional distribution is in good agreement with the autofluorescent lysosomal
      storage and cell loss patterns found in brains from CLN7-defective patients.
      Overall, these data highlight lysosomes as the primary site of action for CLN7,
      and suggest that the pathophysiology underpinning CLN7-associated vLINCL is a
      cell-autonomous process.

PMID- 20826448
TI  - Reduced striatal dopamine underlies the attention system dysfunction in
      neurofibromatosis-1 mutant mice.
AB  - Learning and behavioral abnormalities are among the most common clinical problems
      in children with the neurofibromatosis-1 (NF1) inherited cancer syndrome. Recent
      studies using Nf1 genetically engineered mice (GEM) have been instructive for
      partly elucidating the cellular and molecular defects underlying these cognitive
      deficits; however, no current model has shed light on the more frequently
      encountered attention system abnormalities seen in children with NF1. Using an
      Nf1 optic glioma (OPG) GEM model, we report novel defects in non-selective and
      selective attention without an accompanying hyperactivity phenotype.
      Specifically, Nf1 OPG mice exhibit reduced rearing in response to novel objects
      and environmental stimuli. Similar to children with NF1, the attention system
      dysfunction in these mice is reversed by treatment with methylphenidate (MPH),
      suggesting a defect in brain catecholamine homeostasis. We further demonstrate
      that this attention system abnormality is the consequence of reduced dopamine
      (DA) levels in the striatum, which is normalized following either MPH or l-dopa
      administration. The reduction in striatal DA levels in Nf1 OPG mice is associated
      with reduced striatal expression of tyrosine hydroxylase, the rate-limited enzyme
      in DA synthesis, without any associated dopaminergic cell loss in the substantia
      nigra. Moreover, we demonstrate a cell-autonomous defect in Nf1+/- dopaminergic
      neuron growth cone areas and neurite extension in vitro, which results in
      decreased dopaminergic cell projections to the striatum in Nf1 OPG mice in vivo.
      Collectively, these data establish abnormal DA homeostasis as the primary
      biochemical defect underlying the attention system dysfunction in Nf1 GEM
      relevant to children with NF1.

PMID- 20826449
TI  - Sudden-onset pancytopenia with intracranial hemorrhage after oxaliplatin
      treatment: a case report and literature review.
AB  - Oxaliplatin is a third-generation platinum compound and has been widely employed
      in the treatment of colorectal cancer. Despite its good efficacy, it is reported
      to induce immune-mediated cytopenia. We report the case of a 78-year-old male
      patient who experienced acute pancytopenia along with coagulopathy and
      intracranial hemorrhage after his 17th course of oxaliplatin. This condition
      appeared immediately after completion of oxaliplatin infusion, and was persistent
      despite aggressive transfusion and treatment with granulocyte colony-stimulating
      factor. The patient died 72 h after the administration of oxaliplatin. The only
      preceding symptom was chills 30 min after initiation of oxaliplatin, although
      steroid was given as premedication. We review the literature describing
      oxaliplatin-induced cytopenia, and discuss the manifestation, immune mechanism
      and treatment of this condition. We conclude that any symptoms that occur during
      infusion of oxaliplatin should not be overlooked but should be taken seriously as
      they may represent 'a little spark that kindles a great fire', and that steroids
      may provide an effective treatment for oxaliplatin-induced cytopenia. However, a
      major complication in our patient may still happen. Further studies for the
      mechanism and the predictive markers of oxaliplatin-induced cytopenia are worthy.

PMID- 20826454
TI  - Pro-cathepsin D interacts with the extracellular domain of the beta chain of LRP1
      and promotes LRP1-dependent fibroblast outgrowth.
AB  - Interactions between cancer cells and fibroblasts are crucial in cancer
      progression. We have previously shown that the aspartic protease cathepsin D
      (cath-D), a marker of poor prognosis in breast cancer that is overexpressed and
      highly secreted by breast cancer cells, triggers mouse embryonic fibroblast
      outgrowth via a paracrine loop. Here, we show the requirement of secreted cath-D
      for human mammary fibroblast outgrowth using a three-dimensional co-culture assay
      with breast cancer cells that do or do not secrete pro-cath-D. Interestingly,
      proteolytically-inactive pro-cath-D remains mitogenic, indicating a mechanism
      involving protein-protein interaction. We identify the low-density lipoprotein
      (LDL) receptor-related protein-1, LRP1, as a novel binding partner for pro-cath-D
      in fibroblasts. Pro-cath-D binds to residues 349-394 of the beta chain of LRP1,
      and is the first ligand of the extracellular domain of LRP1beta to be identified.
      We show that pro-cath-D interacts with LRP1beta in cellulo. Interaction occurs at
      the cell surface, and overexpressed LRP1beta directs pro-cath-D to the lipid
      rafts. Our results reveal that the ability of secreted pro-cath-D to promote
      human mammary fibroblast outgrowth depends on LRP1 expression, suggesting that
      pro-cath-D-LRP1beta interaction plays a functional role in the outgrowth of
      fibroblasts. Overall, our findings strongly suggest that pro-cath-D secreted by
      epithelial cancer cells promotes fibroblast outgrowth in a paracrine LRP1
      dependent manner in the breast tumor microenvironment.

PMID- 20826455
TI  - PEX11 family members are membrane elongation factors that coordinate peroxisome
      proliferation and maintenance.
AB  - Dynamic changes of membrane structure are intrinsic to organelle morphogenesis
      and homeostasis. Ectopic expression of proteins of the PEX11 family from yeast,
      plant or human lead to the formation of juxtaposed elongated peroxisomes
      (JEPs),which is evocative of an evolutionary conserved function of these proteins
      in membrane tubulation. Microscopic examinations reveal that JEPs are composed of
      independent elongated peroxisomes with heterogeneous distribution of matrix
      proteins. We established the homo- and heterodimerization properties of the human
      PEX11 proteins and their interaction with the fission factor hFis1, which is
      known to recruit the GTPase DRP1 to the peroxisomal membrane. We show that excess
      of hFis1 but not of DRP1 is sufficient to fragment JEPs into normal round-shaped
      organelles, and illustrate the requirement of microtubules for JEP formation. Our
      results demonstrate that PEX11-induced JEPs represent intermediates in the
      process of peroxisome membrane proliferation and that hFis1 is the limiting
      factor for progression. Hence, we propose a model for a conserved role of PEX11
      proteins in peroxisome maintenance through peroxisome polarization, membrane
      elongation and segregation.

PMID- 20826457
TI  - Decrease of sialic acid residues as an eat-me signal on the surface of apoptotic
      lymphocytes.
AB  - The silent clearance of apoptotic cells is essential for cellular homeostasis in
      multicellular organisms, and several mediators of apoptotic cell recognition have
      been identified. However, the distinct mechanisms involved are not fully
      deciphered yet. We analyzed alterations of the glycocalyx on the surfaces of
      apoptotic cells and its impact for engulfment. After apoptosis induction of
      lymphocytes, a decrease of alpha2,6-terminal sialic acids and sialic acids in
      alpha2,3-linkage with galactose was observed. Similar changes were to be found on
      the surface of apoptotic membrane blebs released during early stages of
      apoptosis, whereas later released blebs showed no impaired, but rather an
      increased, exposure of sialic acids. We detected an exposure of fucose residues
      on the surface of apoptotic-cell-derived membrane blebs. Cleavage by
      neuraminidase of sialic acids, as well as lectin binding to sialic acids on the
      surfaces, enhanced the engulfment of apoptotic cells and blebs. Interestingly,
      even viable lymphoblasts were engulfed in an autologous cell system after
      neuraminidase treatment. Similarly, the engulfment of resting apoptotic
      lymphocytes was augmented after neuraminidase treatment. However, the engulfment
      of resting viable lymphocytes was not significantly enhanced after neuraminidase
      treatment. Our findings support the importance of the glycocalyx, notably the
      terminal sialic acids, in the regulation of apoptotic cell clearance. Thus,
      depending on cell type and activation status, changes in surface glycosylation
      can either directly mediate cellular engulfment or enhance phagocytosis by
      cooperation with further engulfment signals.

PMID- 20826456
TI  - Developmental regulation and extracellular release of a VSG expression-site
      associated gene product from Trypanosoma brucei bloodstream forms.
AB  - Trypanosomes evade host immunity by exchanging variant surface glycoprotein (VSG)
      coats. VSG genes are transcribed from telomeric expression sites, which contain a
      diverse family of expression-site-associated genes (ESAGs). We have discovered
      that the mRNAs for one ESAG family, ESAG9, are strongly developmentally
      regulated, being enriched in stumpy forms, a life-cycle stage in the mammalian
      bloodstream that is important for the maintenance of chronic parasite infections
      and for tsetse transmission. ESAG9 gene sequences are highly diverse in the
      genome and encode proteins with weak similarity to the massively diverse MASP
      proteins in Trypanosoma cruzi. We demonstrate that ESAG9 proteins are modified by
      N-glycosylation and can be shed to the external milieu, this being dependent upon
      coexpression with at least one other family member. The expression profile and
      extracellular release of ESAG9 proteins represents a novel and unexpected aspect
      of the transmission biology of trypanosomes in their mammalian host. We suggest
      that these molecules might interact with the external environment, with possible
      implications for infection chronicity or parasite transmission.

PMID- 20826458
TI  - The nonsense-mediated decay pathway maintains synapse architecture and synaptic
      vesicle cycle efficacy.
AB  - A systematic Drosophila forward genetic screen for photoreceptor synaptic
      transmission mutants identified no-on-and-no-off transient C (nonC) based on loss
      of retinal synaptic responses to light stimulation. The cloned gene encodes
      phosphatidylinositol-3-kinase-like kinase (PIKK) Smg1, a regulatory kinase of the
      nonsense-mediated decay (NMD) pathway. The Smg proteins act in an mRNA quality
      control surveillance mechanism to selectively degrade transcripts containing
      premature stop codons, thereby preventing the translation of truncated proteins
      with dominant-negative or deleterious gain-of-function activities. At the
      neuromuscular junction (NMJ) synapse, an extended allelic series of Smg1 mutants
      show impaired structural architecture, with decreased terminal arbor size,
      branching and synaptic bouton number. Functionally, loss of Smg1 results in a
      ~50% reduction in basal neurotransmission strength, as well as progressive
      transmission fatigue and greatly impaired synaptic vesicle recycling during high
      frequency stimulation. Mutation of other NMD pathways genes (Upf2 and Smg6)
      similarly impairs neurotransmission and synaptic vesicle cycling. These findings
      suggest that the NMD pathway acts to regulate proper mRNA translation to
      safeguard synapse morphology and maintain the efficacy of synaptic function.

PMID- 20826459
TI  - The Na+/H+ exchanger Nhx1p regulates the initiation of Saccharomyces cerevisiae
      vacuole fusion.
AB  - Nhx1p is a Na(+)(K(+))/H(+) antiporter localized at the vacuolar membrane of the
      yeast Saccharomyces cerevisiae. Nhx1p regulates the acidification of cytosol and
      vacuole lumen, and is involved in membrane traffic from late endosomes to the
      vacuole. Deletion of the gene leads to aberrant vacuolar morphology and defective
      vacuolar protein sorting. These phenotypes are hallmarks of malfunctioning
      vacuole homeostasis and indicate that membrane fusion is probably altered. Here,
      we investigated the role of Nhx1p in the regulation of homotypic vacuole fusion.
      Vacuoles isolated from nhx1Delta yeast showed attenuated fusion. Assays
      configured to differentiate between the first round of fusion and ongoing rounds
      showed that nhx1Delta vacuoles were only defective in the first round of fusion,
      suggesting that Nhx1p regulates an early step in the pathway. Although fusion was
      impaired on nhx1Delta vacuoles, SNARE complex formation was indistinguishable
      from wild-type vacuoles. Fusion could be rescued by adding the soluble SNARE
      Vam7p. However, Vam7p only activated the first round of nhx1Delta vacuole fusion.
      Once fusion was initiated, nhx1Delta vacuoles appeared behave in a wild-type
      manner. Complementation studies showed that ion transport function was required
      for Nhx1p-mediated support of fusion. In addition, the weak base chloroquine
      restored nhx1Delta fusion to wild-type levels. Together, these data indicate that
      Nhx1p regulates the initiation of fusion by controlling vacuole lumen pH.

PMID- 20826461
TI  - The role of Schizosaccharomyces pombe dma1 in spore formation during meiosis.
AB  - Meiosis is a specialised form of the cell cycle that gives rise to haploid
      gametes. In Schizosaccharomyces pombe, the products of meiosis are four spores,
      which are formed by encapsulation of the four meiosis II nuclei within the
      cytoplasm of the zygote produced by fusion of the mating cells. The S. pombe
      spindle pole body is remodelled during meiosis II and membrane vesicles are then
      recruited there to form the forespore membrane, which encapsulates the haploid
      nucleus to form a prespore. Spore wall material is then deposited, giving rise to
      the mature spore. The septation initiation network is required to coordinate
      cytokinesis and mitosis in the vegetative cycle and for spore formation in the
      meiotic cycle. We have investigated the role of the SIN regulator dma1p in
      meiosis; we find that although both meiotic divisions occur in the absence of
      dma1p, asci frequently contain fewer than four spores, which are larger than in
      wild-type meiosis. Our data indicate that dma1p acts in parallel to the leading
      edge proteins and septins to assure proper formation for the forespore membrane.
      Dma1p also contributes to the temporal regulation of the abundance of the meiosis
      specific SIN component mug27p.

PMID- 20826460
TI  - Regulation of bile canalicular network formation and maintenance by AMP-activated
      protein kinase and LKB1.
AB  - AMP-activated protein kinase (AMPK), a cellular metabolic sensor, is essential in
      energy regulation and metabolism. Hepatocyte polarization during liver
      development and regeneration parallels increased metabolism. The current study
      investigates the effects of AMPK and its upstream activator LKB1 on polarity and
      bile canalicular network formation and maintenance in collagen sandwich cultures
      of rat hepatocytes. Immunostaining for the apical protein ABCB1 and the tight
      junction marker occludin demonstrated that canalicular network formation is
      sequential and is associated with activation of AMPK and LKB1. AMPK and LKB1
      activators accelerated canalicular network formation. Inhibition of AMPK or LKB1
      by dominant-negative AMPK or kinase-dead LKB1 constructs blocked canalicular
      network formation. AICAR and 2-deoxyglucose, which activate AMPK, circumvented
      the inhibitory effect of kinase-dead LKB1 on canalicular formation, indicating
      that AMPK directly affects canalicular network formation. After the canalicular
      network was formed, inhibition of AMPK and LKB1 by dominant-negative AMPK or
      kinase-dead LKB1 constructs resulted in loss of canalicular network, indicating
      that AMPK and LKB1 also participate in network maintenance. In addition,
      activation of AMPK and LKB1 prevented low-Ca(2+)-mediated disruption of the
      canalicular network and tight junctions. These studies reveal that AMPK and its
      upstream kinase, LKB1, regulate canalicular network formation and maintenance.

PMID- 20826462
TI  - Src-dependent phosphorylation of ROCK participates in regulation of focal
      adhesion dynamics.
AB  - When a cell migrates, the RhoA-ROCK-mediated contractile signal is suppressed in
      the leading edge to allow dynamic adhesions for protrusion. However, several
      studies have reported that RhoA is indeed active in the leading edge of a
      migrating cell during serum stimulation. Here, we present evidence that
      regulation of ROCKII phosphorylation at the Y722 site in peripheral focal
      contacts is crucial for controlling the turnover of the focal adhesion (FA)
      complex uncoupled from RhoA activation during serum-stimulated migration.
      However, this phosphorylation control is dispensable for migration when RhoA is
      downregulated in cells treated with platelet-derived growth factor (PDGF). We
      further present evidence that ROCKII is phosphorylated by Src in FAs and this
      phosphorylation event decreases RhoA binding activity of ROCKII. Lack of this
      regulatory control leads to sustained myosin-mediated contractility and FA
      elongation during lysophosphatidic acid (LPA) stimulation. Altogether, our data
      suggest that Src-dependent ROCKII phosphorylation provides a means of tuning
      contractility required for FAs dynamics when RhoA is active.

PMID- 20826463
TI  - Arg206 of SNAP-25 is essential for neuroexocytosis at the Drosophila melanogaster
      neuromuscular junction.
AB  - An analysis of SNAP-25 isoform sequences indicates that there is a highly
      conserved arginine residue (198 in vertebrates, 206 in the genus Drosophila)
      within the C-terminal region, which is cleaved by botulinum neurotoxin A, with
      consequent blockade of neuroexocytosis. The possibility that it may play an
      important role in the function of the neuroexocytosis machinery was tested at
      neuromuscular junctions of Drosophila melanogaster larvae expressing SNAP-25 in
      which Arg206 had been replaced by alanine. Electrophysiological recordings of
      spontaneous and evoked neurotransmitter release under different conditions as
      well as testing for the assembly of the SNARE complex indicate that this residue,
      which is at the P(1)' position of the botulinum neurotoxin A cleavage site, plays
      an essential role in neuroexocytosis. Computer graphic modelling suggests that
      this arginine residue mediates protein-protein contacts within a rosette of SNARE
      complexes that assembles to mediate the fusion of synaptic vesicles with the
      presynaptic plasma membrane.

PMID- 20826464
TI  - AT-1 is the ER membrane acetyl-CoA transporter and is essential for cell
      viability.
AB  - The transient or permanent modification of nascent proteins in the early
      secretory pathway is an essential cellular function that ensures correct folding
      and maturation of membrane and secreted proteins. We have recently described a
      new form of post-translational regulation of the membrane protein beta-site APP
      cleaving enzyme 1 (BACE1) involving transient lysine acetylation in the lumen of
      the endoplasmic reticulum (ER). The essential components of this process are two
      ER-based acetyl-CoA:lysine acetyltransferases, ATase1 and ATase2, and a membrane
      transporter that translocates acetyl-CoA into the lumen of the ER. Here, we
      report the functional identification of acetyl-CoA transporter 1 (AT-1) as the ER
      membrane acetyl-CoA transporter. We show that AT-1 regulates the acetylation
      status of ER-transiting proteins, including the membrane proteins BACE1, low
      density lipoprotein receptor and amyloid precursor protein (APP). Finally, we
      show that AT-1 is essential for cell viability as its downregulation results in
      widespread cell death and induction of features characteristic of autophagy.

PMID- 20826465
TI  - The overexpression of the putative gut stem cell marker Musashi-1 induces
      tumorigenesis through Wnt and Notch activation.
AB  - The RNA-binding protein Musashi-1 (Msi1) has been proposed as a marker of
      intestinal epithelial stem cells. These cells are responsible for the continuous
      renewal of the intestinal epithelium. Although the function of Msi1 has been
      studied in several organs from different species and in mammalian cell lines, its
      function and molecular regulation in mouse intestinal epithelium progenitor cells
      are still undefined. We describe here that, in these cells, the expression of
      Msi1 is regulated by the canonical Wnt pathway, through a mechanism involving a
      functional Tcf/Lef binding site on its promoter. An in vitro study in intestinal
      epithelium primary cultures showed that Msi1 overexpression promotes progenitor
      proliferation and activates Wnt and Notch pathways. Moreover, Msi1-overexpressing
      cells exhibit tumorigenic properties in xenograft experiments. These data point
      to a positive feedback loop between Msi1 and Wnt in intestinal epithelial
      progenitors. They also suggest that Msi1 has oncogenic properties in these cells,
      probably through induction of both the Wnt and Notch pathways.

PMID- 20826467
TI  - Transmembrane domains control exclusion of membrane proteins from clathrin-coated
      pits.
AB  - Efficient sorting of proteins is essential to allow transport between
      intracellular compartments while maintaining their specific composition. During
      endocytosis, membrane proteins can be concentrated in endocytic vesicles by
      specific interactions between their cytoplasmic domains and cytosolic coat
      proteins. It is, however, unclear whether they can be excluded from transport
      vesicles and what the determinants for this sorting could be. Here, we show that
      in the absence of cytosolic sorting signals, transmembrane domains control the
      access of surface proteins to endosomal compartments. They act in particular by
      determining the degree of exclusion of membrane proteins from endocytic clathrin
      coated vesicles. When cytosolic endocytosis signals are present, it is the
      combination of cytosolic and transmembrane determinants that ultimately controls
      the efficiency with which a given transmembrane protein is endocytosed.

PMID- 20826466
TI  - WLS-dependent secretion of WNT3A requires Ser209 acylation and vacuolar
      acidification.
AB  - Wnt proteins are secreted post-translationally modified proteins that signal
      locally to regulate development and proliferation. The production of bioactive
      Wnts requires a number of dedicated factors in the secreting cell whose
      coordinated functions are not fully understood. A screen for small molecules
      identified inhibitors of vacuolar acidification as potent inhibitors of Wnt
      secretion. Inhibition of the V-ATPase or disruption of vacuolar pH gradients by
      diverse drugs potently inhibited Wnt/beta-catenin signaling both in cultured
      human cells and in vivo, and impaired Wnt-regulated convergent extension
      movements in Xenopus embryos. WNT secretion requires its binding to the carrier
      protein wntless (WLS); we find that WLS is ER-resident in human cells and WNT3A
      binding to WLS requires PORCN-dependent lipid modification of WNT3A at serine
      209. Inhibition of vacuolar acidification results in accumulation of the WNT3A
      WLS complex both in cells and at the plasma membrane. Modeling predictions
      suggest that WLS has a lipid-binding beta-barrel that is similar to the lipocalin
      family fold. We propose that WLS binds Wnts in part through a lipid-binding
      domain, and that vacuolar acidification is required to release palmitoylated
      WNT3A from WLS in secretory vesicles, possibly to facilitate transfer of WNT3A to
      a soluble carrier protein.

PMID- 20826468
TI  - Hearing in the African lungfish (Protopterus annectens): pre-adaptation to
      pressure hearing in tetrapods?
AB  - Lungfishes are the closest living relatives of the tetrapods, and the ear of
      recent lungfishes resembles the tetrapod ear more than the ear of ray-finned
      fishes and is therefore of interest for understanding the evolution of hearing in
      the early tetrapods. The water-to-land transition resulted in major changes in
      the tetrapod ear associated with the detection of air-borne sound pressure, as
      evidenced by the late and independent origins of tympanic ears in all of the
      major tetrapod groups. To investigate lungfish pressure and vibration detection,
      we measured the sensitivity and frequency responses of five West African lungfish
      (Protopterus annectens) using brainstem potentials evoked by calibrated sound and
      vibration stimuli in air and water. We find that the lungfish ear has good low
      frequency vibration sensitivity, like recent amphibians, but poor sensitivity to
      air-borne sound. The skull shows measurable vibrations above 100 Hz when
      stimulated by air-borne sound, but the ear is apparently insensitive at these
      frequencies, suggesting that the lungfish ear is neither adapted nor pre-adapted
      for aerial hearing. Thus, if the lungfish ear is a model of the ear of early
      tetrapods, their auditory sensitivity was limited to very low frequencies on
      land, mostly mediated by substrate-borne vibrations.

PMID- 20826469
TI  - Male dance moves that catch a woman's eye.
AB  - Male movements serve as courtship signals in many animal species, and may
      honestly reflect the genotypic and/or phenotypic quality of the individual.
      Attractive human dance moves, particularly those of males, have been reported to
      show associations with measures of physical strength, prenatal androgenization
      and symmetry. Here we use advanced three-dimensional motion-capture technology to
      identify possible biomechanical differences between women's perceptions of 'good'
      and 'bad' male dancers. Nineteen males were recorded using the 'Vicon' motion
      capture system while dancing to a basic rhythm; controlled stimuli in the form of
      avatars were then created in the form of 15 s video clips, and rated by 39
      females for dance quality. Initial analyses showed that 11 movement variables
      were significantly positively correlated with perceived dance quality. Linear
      regression subsequently revealed that three movement measures were key predictors
      of dance quality; these were variability and amplitude of movements of the neck
      and trunk, and speed of movements of the right knee. In summary, we have
      identified specific movements within men's dance that influence women's
      perceptions of dancing ability. We suggest that such movements may form honest
      signals of male quality in terms of health, vigour or strength, though this
      remains to be confirmed.

PMID- 20826470
TI  - An indigenous religious ritual selects for resistance to a toxicant in a
      livebearing fish.
AB  - Human-induced environmental change can affect the evolutionary trajectory of
      populations. In Mexico, indigenous Zoque people annually introduce barbasco, a
      fish toxicant, into the Cueva del Azufre to harvest fish during a religious
      ceremony. Here, we investigated tolerance to barbasco in fish from sites exposed
      and unexposed to the ritual. We found that barbasco tolerance increases with body
      size and differs between the sexes. Furthermore, fish from sites exposed to the
      ceremony had a significantly higher tolerance. Consequently, the annual ceremony
      may not only affect population structure and gene flow among habitat types, but
      the increased tolerance in exposed fish may indicate adaptation to human cultural
      practices in a natural population on a very small spatial scale.

PMID- 20826471
TI  - Eastward from Africa: palaeocurrent-mediated chameleon dispersal to the
      Seychelles islands.
AB  - Madagascar and the Seychelles are Gondwanan remnants currently isolated in the
      Indian Ocean. In the Late Cretaceous, these islands were joined with India to
      form the Indigascar landmass, which itself then split into its three component
      parts around the start of the Tertiary. This history is reflected in the biota of
      the Seychelles, which appears to contain examples of both vicariance- and
      dispersal-mediated divergence from Malagasy or Indian sister taxa. One lineage
      for which this has been assumed but never thoroughly tested is the Seychellean
      tiger chameleon, a species assigned to the otherwise Madagascar-endemic genus
      Calumma. We present a multi-locus phylogenetic study of chameleons, and find that
      the Seychellean species is actually the sister taxon of a southern African clade
      and requires accomodation in its own genus as Archaius tigris. Divergence dating
      and biogeographic analyses indicate an origin by transoceanic dispersal from
      Africa to the Seychelles in the Eocene-Oligocene, providing, to our knowledge,
      the first such well-documented example and supporting novel palaeocurrent
      reconstructions.

PMID- 20826472
TI  - Suction component in adhesion of mushroom-shaped microstructure.
AB  - To shed light on the role of suction in adhesion of microstructure with mushroom
      shaped terminal elements, we compared pull-off forces measured at different
      retraction velocities on structured and smooth surfaces under different pressure
      conditions. The results obtained allow us to suggest that suction may contribute
      up to 10 per cent of the pull-off force measured on the structured surfaces at
      high velocities. We therefore conclude that the attachment ability of this
      biomimetic adhesive must not be solely based on van der Waals forces. Our
      experiments also suggest a change in visco-elastic properties of the structured
      surfaces compared with the bulk material. Based on the results obtained, it is
      assumed that this adhesive may be suitable in dynamic pick-and-drop processes
      even under vacuum conditions at which sufficiently high adhesive capability is
      maintained.

PMID- 20826473
TI  - A framework for understanding the architecture of collective movements using
      pairwise analyses of animal movement data.
AB  - The study of collective or group-level movement patterns can provide insight
      regarding the socio-ecological interface, the evolution of self-organization and
      mechanisms of inter-individual information exchange. The suite of drivers
      influencing coordinated movement trajectories occur across scales, resulting from
      regular annual, seasonal and circadian stimuli and irregular intra- or
      interspecific interactions and environmental encounters acting on individuals.
      Here, we promote a conceptual framework with an associated statistical machinery
      to quantify the type and degree of synchrony, spanning absence to complete, in
      pairwise movements. The application of this framework offers a foundation for
      detailed understanding of collective movement patterns and causes. We emphasize
      the use of Fourier and wavelet approaches of measuring pairwise movement
      properties and illustrate them with simulations that contain different types of
      complexity in individual movement, correlation in movement stochasticity, and
      transience in movement relatedness. Application of this framework to movements of
      free-ranging African elephants (Loxodonta africana) provides unique insight on
      the separate roles of sociality and ecology in the fission-fusion society of
      these animals, quantitatively characterizing the types of bonding that occur at
      different levels of social relatedness in a movement context. We conclude with a
      discussion about expanding this framework to the context of larger (greater than
      three) groups towards understanding broader population and interspecific
      collective movement patterns and their mechanisms.

PMID- 20826476
TI  - Limited interactions in flocks: relating model simulations to empirical data.
AB  - The mechanism of self-organization resulting in coordinated collective motion has
      received wide attention from a range of scientists interested in both its
      technical and biological relevance. Models have been highly influential in
      highlighting how collective motion can be produced from purely local interactions
      between individuals. Typical models in this field are termed 'metric' because
      each individual only reacts to conspecifics within a fixed distance. A recent
      large-scale study has, however, provided evidence that interactions ruling
      collective behaviour occur between a fixed number of nearest neighbours
      ('topological' framework). Despite their importance in clarifying the nature of
      the mechanism underlying animal interactions, these findings have yet to be
      produced by either metric or topological models. Here, we present an original
      individual-based model of collective animal motion that reproduces the previous
      findings. Our approach bridges the current gap between previous model analysis
      and recent evidence, and presents a framework for further study.

PMID- 20826474
TI  - Safety paradigm: genetic evaluation of therapeutic grade human embryonic stem
      cells.
AB  - The use of stem cells for regenerative medicine has captured the imagination of
      the public, with media attention contributing to rising expectations of clinical
      benefits. Human embryonic stem cells (hESCs) are the best model for capital
      investment in stem cell therapy and there is a clear need for their robust
      genetic characterization before scaling-up cell expansion for that purpose. We
      have to be certain that the genome of the starting material is stable and normal,
      but the limited resolution of conventional karyotyping is unable to give us such
      assurance. Advanced molecular cytogenetic technologies such as array comparative
      genomic hybridization for identifying chromosomal imbalances, and single
      nucleotide polymorphism analysis for identifying ethnic background and loss of
      heterozygosity should be introduced as obligatory diagnostic tests for each newly
      derived hESC line before it is deposited in national stem cell banks. If this new
      quality standard becomes a requirement, as we are proposing here, it would
      facilitate and accelerate the banking process, since end-users would be able to
      select the most appropriate line for their particular application, thus improving
      efficiency and streamlining the route to manufacturing therapeutics. The
      pharmaceutical industry, which may use hESC-derived cells for drug screening,
      should not ignore their genomic profile as this may risk misinterpretation of
      results and significant waste of resources.

PMID- 20826475
TI  - Rho-associated kinase-dependent contraction of stress fibres and the organization
      of focal adhesions.
AB  - Stress fibres and associated focal adhesions in cells constitute a contractile
      apparatus that regulates cell motility and contraction. Rho-kinase, an effector
      molecule of small GTPases, regulates non-muscle cell motility and contractility.
      Rho-kinase mediates the contraction of stress fibres in a Ca(2+)-independent
      manner, and is responsible for slower and more finely tuned contraction of stress
      fibres than that regulated by myosin light chain kinase activity in living cells.
      The specific inhibition of the Rho-kinase activity causes cells to not only lose
      their stress fibres and focal adhesions, but also to appear to lose their
      cytoplasmic tension. Activated Rho-kinase is also involved in the organization of
      newly formed stress fibres and focal adhesions in living cells.

PMID- 20826477
TI  - Regenerative medicine. Opportunities and challenges: a brief overview.
AB  - Regenerative medicine is a new multi-disciplinary field aiming at the repair or
      replacement of disease body parts. The field is progressing at an unprecedented
      pace and although the opportunities are immense, many hurdles lie ahead. This
      brief review analyses the opportunities and challenges faced by regenerative
      medicine.

PMID- 20826478
TI  - Regenerative nanomedicines: an emerging investment prospective?
AB  - Cells respond to their structural surrounding and within nanostructures exhibit
      unique proliferative and differentiation properties. The application of
      nanotechnologies to the field of regenerative medicine offers the potential to
      direct cell fate, target the delivery of cells and reduce immune rejection (via
      encapsulation), thereby supporting the development of regenerative medicines. The
      overall objective of any therapy is the delivery of the product not just into the
      clinic but also to patients on a routine basis. Such a goal typically requires a
      commercial vehicle and substantial levels of investment in scientific, clinical,
      regulatory and business expertise, resources, time and funding. Therefore, this
      paper focuses on some of the challenges facing this emerging industry, including
      investment by the venture capital community.

PMID- 20826479
TI  - Reproductive state affects reliance on public information in sticklebacks.
AB  - The degree to which animals use public and private sources of information has
      important implications for research in both evolutionary ecology and cultural
      evolution. While researchers are increasingly interested in the factors that lead
      individuals to vary in the manner in which they use different sources of
      information, to date little is known about how an animal's reproductive state
      might affect its reliance on social learning. Here, we provide experimental
      evidence that in foraging ninespine sticklebacks (Pungitius pungitius), gravid
      females increase their reliance on public information generated by feeding
      demonstrators in choosing the richer of two prey patches than non-reproductive
      fish, while, in contrast, reproductive males stop using public information.
      Subsequent experiments revealed reproductive males to be more efficient asocial
      foragers, less risk-averse and generally less social than both reproductive
      females and non-reproductives. These findings are suggestive of adaptive switches
      in reliance on social and asocial sources of information with reproductive
      condition, and we discuss the differing costs of reproduction and the proximate
      mechanisms that may underlie these differences in information use. Our findings
      have important implications for our understanding of adaptive foraging strategies
      in animals and for understanding the way information diffuses through
      populations.

PMID- 20826480
TI  - Knower-guesser differentiation in ravens: others' viewpoints matter.
AB  - Differentiating between individuals with different knowledge states is an
      important step in child development and has been considered as a hallmark in
      human evolution. Recently, primates and corvids have been reported to pass knower
      guesser tasks, raising the possibility of mental attribution skills in non-human
      animals. Yet, it has been difficult to distinguish 'mind-reading' from behaviour
      reading alternatives, specifically the use of behavioural cues and/or the
      application of associatively learned rules. Here, I show that ravens (Corvus
      corax) observing an experimenter hiding food are capable of predicting the
      behaviour of bystanders that had been visible at both, none or just one of two
      caching events. Manipulating the competitors' visual field independently of the
      view of the test-subject resulted in an instant drop in performance, whereas
      controls for behavioural cues had no such effect. These findings indicate that
      ravens not only remember whom they have seen at caching but also take into
      account that the other's view was blocked. Notably, it does not suffice for the
      birds to associate specific competitors with specific caches. These results
      support the idea that certain socio-ecological conditions may select for similar
      cognitive abilities in distantly related species and that some birds have evolved
      analogous precursors to a human theory-of-mind.

PMID- 20826481
TI  - Temporal recalibration of vision.
AB  - Our sense of relative timing is malleable. For instance, visual signals can be
      made to seem synchronous with earlier sounds following prolonged exposure to an
      environment wherein auditory signals precede visual ones. Similarly, actions can
      be made to seem to precede their own consequences if an artificial delay is
      imposed for a period, and then removed. Here, we show that our sense of relative
      timing for combinations of visual changes is similarly pliant. We find that
      direction reversals can be made to seem synchronous with unusually early colour
      changes after prolonged exposure to a stimulus wherein colour changes precede
      direction changes. The opposite effect is induced by prolonged exposure to colour
      changes that lag direction changes. Our data are consistent with the proposal
      that our sense of timing for changes encoded by distinct sensory mechanisms can
      adjust, at least to some degree, to the prevailing environment. Moreover, they
      reveal that visual analyses of colour and motion are sufficiently independent for
      this to occur.

PMID- 20826482
TI  - Individual behaviour in firebugs (Pyrrhocoris apterus).
AB  - The concept of animal personalities has recently become of major interest as
      researchers began to wonder why animals within a given population show consistent
      behaviour across situations and contexts, what led to the evolution of such
      behavioural inflexibility and what mechanisms might underlie the phenomenon. A
      recent model explains individual differences in a population as the result of
      trade-off between present and future reproduction. We tested this model on the
      two wing morphs, i.e. short-winged (brachypterous) and long-winged (macropterous)
      specimens of the firebug (Pyrrhocoris apterus). Since it has been already
      demonstrated that the two wing morphs differ in their life-history strategies,
      this species is an ideal subject to test whether the specimens with different
      life-history strategies have different personalities as well. The results show
      that individuals behave consistently over time and across contexts, meaning
      observed bugs do have personalities. We also have found that in females, the two
      wing morphs have different personalities supporting the theoretical predictions,
      i.e. winged ones, which are supposed to have lower future reproductive value, are
      braver and more exploratory. We found no difference between the morphs in males.
      Differences in reproductive investment might explain this discrepancy between the
      sexes.

PMID- 20826483
TI  - Evolutionary inheritance of elemental stoichiometry in phytoplankton.
AB  - The elemental composition of phytoplankton is a fusion of the evolutionary
      history of the host and plastid, resulting in differences in genetic constraints
      and selection pressures associated with environmental conditions. The
      evolutionary inheritance hypothesis predicts similarities in elemental
      composition within related taxonomic lineages of phytoplankton. To test this
      hypothesis, we measured the elemental composition (C, N, P, S, K, Mg, Ca, Sr, Fe,
      Mn, Zn, Cu, Co, Cd and Mo) of 14 phytoplankton species and combined these with
      published data from 15 more species from both marine and freshwater environments
      grown under nutrient-replete conditions. The largest differences in the elemental
      profiles of the species distinguish between the prokaryotic Cyanophyta and
      primary endosymbiotic events that resulted in the green and red plastid lineages.
      Smaller differences in trace element stoichiometry within the red and green
      plastid lineages are consistent with changes in trace elemental stoichiometry
      owing to the processes associated with secondary endosymbioses and inheritance by
      descent with modification.

PMID- 20826484
TI  - Translating environmental gradients into discontinuous reaction norms via hormone
      signalling in a polyphenic butterfly.
AB  - Polyphenisms-the expression of discrete phenotypic morphs in response to
      environmental variation-are examples of phenotypic plasticity that may
      potentially be adaptive in the face of predictable environmental heterogeneity.
      In the butterfly Bicyclus anynana, we examine the hormonal regulation of
      phenotypic plasticity that involves divergent developmental trajectories into
      distinct adult morphs for a suite of traits as an adaptation to contrasting
      seasonal environments. This polyphenism is induced by temperature during
      development and mediated by ecdysteroid hormones. We reared larvae at separate
      temperatures spanning the natural range of seasonal environments and measured
      reaction norms for ecdysteroids, juvenile hormones (JHs) and adult fitness
      traits. Timing of peak ecdysteroid, but not JH titres, showed a binary response
      to the linear temperature gradient. Several adult traits (e.g. relative abdomen
      mass) responded in a similar, dimorphic manner, while others (e.g. wing pattern)
      showed a linear response. This study demonstrates that hormone dynamics can
      translate a linear environmental gradient into a discrete signal and, thus, that
      polyphenic differences between adult morphs can already be programmed at the
      stage of hormone signalling during development. The range of phenotypic responses
      observed within the suite of traits indicates both shared regulation and
      independent, trait-specific sensitivity to the hormone signal.

PMID- 20826485
TI  - Phylogeography of microbial phototrophs in the dry valleys of the high Himalayas
      and Antarctica.
AB  - High-elevation valleys in dry areas of the Himalayas are among the most extreme,
      yet least explored environments on Earth. These barren, rocky valleys are
      subjected to year-round temperature fluctuations across the freezing point and
      very low availability of water and nutrients, causing previous workers to
      hypothesize that no photoautotrophic life (primary producers) exists in these
      locations. However, there has been no work using modern biogeochemical or culture
      independent molecular methods to test the hypothesis that photoautotrophs are
      absent from high Himalayan soil systems. Here, we show that although microbial
      biomass levels are as low as those of the Dry Valleys of Antarctica, there are
      abundant microbial photoautotrophs, displaying unexpected phylogenetic diversity,
      in barren soils from just below the permanent ice line of the central Himalayas.
      Furthermore, we discovered that one of the dominant algal clades from the high
      Himalayas also contains the dominant algae in culture-independent surveys of both
      soil and ice samples from the Dry Valleys of Antarctica, revealing an unexpected
      link between these environmentally similar but geographically very distant
      systems. Phylogenetic and biogeographic analyses demonstrated that although this
      algal clade is globally distributed to other high-altitude and high-latitude
      soils, it shows significant genetic isolation by geographical distance patterns,
      indicating local adaptation and perhaps speciation in each region. Our results
      are the first to demonstrate the remarkable similarities of microbial life of
      arid soils of Antarctica and the high Himalayas. Our findings are a starting
      point for future comparative studies of the dry valleys of the Himalayas and
      Antarctica that will yield new insights into the cold and dry limits to life on
      Earth.

PMID- 20826486
TI  - Absence of mammals and the evolution of New Zealand grasses.
AB  - Anthropogenic alteration of biotic distributions and disturbance regimes has
      dramatically changed the evolutionary context for the differentiation of species
      traits. Some of the most striking examples in recent centuries have been on
      islands where flightless birds, which evolved in the absence of mammalian
      carnivores, have been decimated following the widespread introduction of exotic
      predators. Until now, no equivalent case has been reported for plants. Here, we
      make use of robust analytical tools and an exceptionally well-sampled molecular
      phylogeny to show that a majority of New Zealand danthonioid grasses (Poaceae)
      may have adapted to the relaxed vertebrate herbivore pressure during the late
      Cenozoic through the development of a distinctive and unusual habit: abscission
      of old leaves. This feature occurs in only about 3 per cent of the world's
      roughly 11,000 grass species and has been empirically shown to increase plant
      productivity but to reduce protection against mammal grazing. This result
      suggests that release from a selective pressure can lead to species radiations.
      This seemingly anachronistic adaptation may represent an overlooked factor
      contributing to the severe decline in the geographical extent and species
      diversity of New Zealand's indigenous grasslands following the introduction of
      herbivorous terrestrial mammals in the 19th century.

PMID- 20826487
TI  - Speed-accuracy trade-offs during foraging decisions in the acellular slime mould
      Physarum polycephalum.
AB  - Speed-accuracy trade-offs (SATs) are thought to be a fundamental feature of
      biological information processing, yet most evidence of SATs comes from animals.
      Here, we examine SATs in the foraging decisions of an acellular, amoeboid
      organism: the slime mould Physarum polycephalum. Slime moulds were given a simple
      discrimination task: selecting the highest-quality food item from a set of three
      options. We investigated the effect of two stressors, light exposure and hunger,
      on the speed and accuracy of decision-making. We also examined the effect of task
      difficulty. When given a difficult discrimination task, stressed individuals tend
      to make faster decisions than non-stressed individuals. This effect was reversed
      in plasmodia given easy discrimination tasks, where stressed individuals made
      slower decisions than non-stressed individuals. We found evidence of SATs, such
      that individuals who made fast decisions were more likely to make costly errors
      by selecting the worst possible food option. Our results suggest that SATs occur
      in a wider range of taxa than previously considered.

PMID- 20826488
TI  - Endemic predators, invasive prey and native diversity.
AB  - Interactions between native diversity and invasive species can be more complex
      than is currently understood. Invasive ant species often substantially reduce
      diversity in the native ants diversity that act as natural control agents for
      pest insects. In Indonesia (on the island of Sulawesi), the third largest cacao
      producer worldwide, we show that a predatory endemic toad (Ingerophrynus
      celebensis) controls invasive ant (Anoplolepis gracilipes) abundance, and
      positively affects native ant diversity. We call this the invasive-naivety effect
      (an opposite of enemy release), whereby alien species may not harbour anti
      predatory defences against a novel native predator. A positive effect of the
      toads on native ants may facilitate their predation on insect vectors of cacao
      diseases. Hence, toads may increase crop yield, but further research is needed on
      this aspect. Ironically, amphibians are globally the most threatened vertebrate
      class and are strongly impacted by the conversion of rainforest to cacao
      plantations in Sulawesi. It is, therefore, crucial to manage cacao plantations to
      maintain these endemic toads, as they may provide critical ecosystem services,
      such as invasion resistance and preservation of native insect diversity.

PMID- 20826489
TI  - Quantitative analysis of verbal expressions in comments from evaluation committee
      reviewers in AIST between fiscal years 2001 and 2008.
AB  - This article discusses the quantitative analysis of verbal expressions of
      comments from the evaluation committee reviewers for 8 years (FY2001-FY2008) at
      the Japanese Public Research Institute, National Institute of Advanced Industrial
      Science and Technology (AIST). First, the terms often appearing in the comment
      sheets were observed. Moreover, gradually increasing terms every year and
      suddenly emerging terms after the beginning of the second research phase are
      examined. Finally, the terms related closely to the output evaluation are
      considered. By properly setting the evaluation items, the comments along a
      specific direction can be obtained from the reviewers. Moreover, the permeation
      of an idea or concept can also be found by measuring the time variance of the
      frequency of specific terms in the comment sheet.

PMID- 20826490
TI  - The use of high doses of oxycodone in an acute palliative care unit.
AB  - A retrospective study of patients who were prescribed controlled-release
      oxycodone (CRO) in a period of 3 years (2006-2008) was performed. A total of 212
      patients were prescribed at discharge CRO for background analgesia; 129, 43, and
      40 patients were prescribed doses of oxycodone of less than 120 mg/day (group L),
      120 to 240 mg/day (group M), and more than 240 mg/day (group L), respectively. No
      differences in gender, primary diagnosis, and pain mechanisms were found, but
      doses were significantly lower in older patients (P < .0005). At discharge,
      adverse effects were mild and only a minority of patients were switched to other
      opioids. This study demonstrated that CRO administered in larger doses was safe
      and effective, showing versatility and flexibility similar to morphine.

PMID- 20826491
TI  - Balancing a changed life situation: the lived experience from next of kin to
      persons with inoperable lung cancer.
AB  - The purpose of this study was to identify and describe the experiences of quality
      of life/life situation among those who were next of kin to persons with
      inoperable lung cancer. Data were collected in qualitative interviews, where 11
      next of kin articulated their lived experiences, and were interpreted through
      interpretive phenomenology. Four themes were identified: changed life situation,
      experiences of uncertainty due to awareness of the ill person's changed health
      status, interpersonal relationships, and false hopes due to health care
      professionals' treatment. These four themes gave a structure presenting the
      essence: balancing a changed life situation. The findings of the study point out
      the importance of promoting support for the next of kin, because they are
      significantly affected by the changed life situation. There is a need to identify
      their needs and to support them.

PMID- 20826492
TI  - Development of a Japanese Benefit Finding scale (JBFS) for patients with cancer.
AB  - The primary aim of this study was to develop a scale to evaluate benefits for
      patients with cancer under treatment in Japan (the Japan Benefit Finding scale
      [JBFS]). The participants were 98 patients with cancer who completed the JBFS,
      which has 26 items, the General Health Questionnaire short version (GHQ 12).
      Factor analysis, structural equation modeling (SEM), and correlation analysis
      were performed. Three key domains were identified: ''Recognition of one's role in
      the family and priorities,'' ''Appreciation for life,'' and ''Faith.'' Validity
      was confirmed by SEM. There was a significant correlation between the JBFS and
      GHQ 12. The reliability and validity are adequate, and the JBFS shows that
      Japanese patients who found benefits in cancer were able to adjust to their
      disease.

PMID- 20826493
TI  - Review of cancer pain management in patients receiving maintenance methadone
      therapy.
AB  - Methadone is commonly used in the treatment of heroin addiction. Patients with a
      history of opioid misuse or on methadone maintenance therapy (MMT) with cancer
      often have difficult to manage pain. We studied 12 patients referred to the
      palliative care service with cancer pain who were on MMT. All had difficult to
      control pain, and a third required 5 or more analgesic agents. Two patients had
      documented ''drug-seeking'' behavior. Methadone was used subcutaneously as an
      analgesic agent in 1 patient. We explore why patients on MMT have difficult to
      manage pain, the optimal management of their pain, and the increasing role of
      methadone as an analgesic agent in cancer pain.

PMID- 20826495
TI  - Access to experimental drugs in terminally ill patients: a new idea?

PMID- 20826494
TI  - Quality of life for children with life-limiting and life-threatening illnesses:
      description and evaluation of a regional, collaborative model for pediatric
      palliative care.
AB  - The care of children in the U.S. with life-limiting illnesses is inadequate.
      Misallocated resources, flawed assumptions and models of care, and a lack of
      appropriate professional education foster a costly, inefficient system that falls
      short of its true potential. This article details the evolution of a regional,
      shared approach to address these issues, the District of Columbia Pediatric
      Palliative Care Collaboration (DCPPCC), and includes its evolution, preliminary
      clinical results, and assessment of barriers encountered.

PMID- 20826496
TI  - A survey of verbal and physical assaults towards psychiatrists in Turkey.
AB  - BACKGROUND: Assaults on health professionals have been an area of burgeoning
      clinical and political interest in recent years. There is now a body of
      literature suggesting that violence towards psychiatrists is more common than to
      other doctors. Thus far the vast majority of research in this area has been
      conducted in Western European and North American clinical settings. For the first
      time, this study examines this issue in the context of Turkish psychiatric
      settings. OBJECTIVE: (i) The study aims to detect the prevalence of verbal and
      physical assaults towards psychiatrists in Turkey. (ii) It aims to compare the
      experience of verbal and physical assaults according to the gender and training
      experience of psychiatrists. (iii) The paper intends to investigate how
      psychiatrists reacted to and appraised the experience of violence. METHODS: A
      questionnaire was prepared to evaluate violence towards psychiatrists (adapted
      from the Overt Agression Scale). The questionaire was administered to psychiatric
      specialists and residents working in state hospitals, research and training
      hospitals, mental health hospitals and university psychiatry clinics. A response
      rate of 93% was achieved with 186 out of 200 psychiatrsits approached completing
      the study questionnaire. RESULTS: Of all the psychiatrists who responded, 71%
      reported having experienced verbal or physical assaults during their professional
      life (verbal assaults only (19.9%), physical assaults only (2.7%) and both
      (48.4%)). Of these, 26% suffered injury to at least a mild degree. There was no
      statistically significant difference in terms of gender and workplace. In spite
      of the extremely high rates of aggression and violence towards psychiatrists,
      roughly 50% perceived these acts a normal part of their job and only 5% formally
      reported the violent incident. CONCLUSION: The majority of psychiatrists
      described having been victims of verbal and physical assaults although half
      perceived aggression and violence as a normal part of their job. Levels of
      reporting of violence were very low in the context of this study. Studies such as
      this provide evidence to inform the development of improved management of
      violence and may encourage psychiatrists to report violence.

PMID- 20826497
TI  - The role of self-esteem for outcome in first-episode psychosis.
AB  - BACKGROUND: Self-esteem may be associated with a wide range of psychiatric
      disorders, including psychotic disorders. However, the relationship between self
      esteem and outcome in psychosis has not been adequately examined, especially
      early in the course of the illness. AIM: The aim of the study was to examine the
      impact of self-esteem in individuals who presented for treatment of a first
      episode of psychosis on outcome early in the course of the illness. METHODS: The
      Self-Esteem Rating Scale (SERS) was administered to 121 individuals with first
      episode psychosis following entry into a specialized programme. Symptoms and the
      Global Assessment of Functioning (GAF) were assessed at six months after
      beginning treatment. A correlational analysis was followed by a linear regression
      controlling for potential confounds. RESULTS: Self-esteem assessed early in the
      course of treatment was positively correlated with GAF at six months (r = 0.281,
      p < 0.01). A linear regression analysis conducted with GAF and depression at
      baseline in addition to gender, pre-morbid adjustment, duration of untreated
      psychosis (DUP), and self-esteem as predictors and GAF at six months as the
      outcome variable revealed only self-esteem to be a significant predictor of GAF
      at six months (beta = 0.290, p < 0.01). However, no association was found between
      self-esteem and remission at six months (beta = 0.003, p > 0.05). CONCLUSION:
      Self-esteem is associated with global functional outcome at six months but not
      with remission of symptoms. Efforts should be made to provide interventions that
      may improve low self-esteem in the attempt to influence functional outcome.

PMID- 20826498
TI  - Gender differences in stressors and reactions to stressors among Jordanian
      university students.
AB  - BACKGROUND: Stress among university students has been a topic of interest for
      researchers and teachers for many years because it affects not only their
      academic performance but also their physiological and psychological health. Male
      and female students perceive and react to stressors differently due to their
      differences in appraising stressful situations. AIMS: The aims of this study were
      to examine differences in the perception of stressors and reactions to stressors
      between male and female Jordanian university students, and to identify the best
      predictors of stressors among them. METHODS: Descriptive cross-sectional design
      was employed. The Student-Life Stress Inventory was used to measure stressors and
      reactions to stressors of 465 male and 485 female Jordanian university students
      recruited through stratified random sampling. RESULTS: There were statistical
      differences between male and female students regarding their perception and
      reactions to stressors. Female students reported a higher perception of stressors
      in frustrations, conflict, pressures and changes, as well as emotional reactions
      to stressors. Male students reported higher behavioural and cognitive reactions
      to stressors than female students. Participation in stress workshops, perception
      of general health, and perception of stress level in general were found to
      predict stressors among male students, while mother's educational level,
      perception of general health, and perception of stress level in general were
      found to predict stressors among female students. CONCLUSIONS: This study showed
      that gender differences in perception of stressors and reactions to stressors are
      similar to previous studies conducted all over the world. Interventions can be
      developed to help students better cope with stress. Conducting specific stress
      training programmes for male and female students will help in reducing stress
      levels.

PMID- 20826499
TI  - Reliability of the Camberwell Assessment of Need for South African mental health
      service users.
AB  - BACKGROUND: The Camberwell Assessment of Need (CAN) is a widely used instrument
      to assess the service needs for people with a severe mental illness. No
      reliability data are available for its use in South Africa. METHOD: Interrater
      and test-retest reliability were documented for a sub-sample of 194 patients
      participating in a needs assessment study among people receiving mental health
      services. Initially, the CAN was administered by one field worker, while another
      observed and also made ratings. The participant was then re-interviewed
      approximately one week after the initial interview. RESULTS: With the exception
      of 'psychotic symptoms' (kappa = -0.4) and 'looking after home' (kappa = 0.008),
      Cohen's kappa coefficients for interrater reliability ranged from 0.150 to 0.760
      for Section 1 of the CAN. Test-retest reliabilities for Section 1 resulted in
      moderate to substantial agreement, with Cohen's kappa coefficient ranging from
      0.25 to 0.81. High correlations were reported for the test-retest reliabilities
      of the remaining sections of the CAN (r = 0.719-0.845). However, the figures for
      the interrater reliabilities were lower and more variable (r = -0.082-0.408).
      CONCLUSION: The results of this study suggest that with additional interviewer
      training, the CAN is a relatively reliable instrument for assessing the needs of
      youths with severe mental illness.

PMID- 20826500
TI  - Multiplicity adjustments in trials with two correlated comparisons of interest.
AB  - Clinical trials investigating the efficacy of two or more doses of an
      experimental treatment compared to a single reference arm are not uncommon. In
      such situations, if each dose is compared to the reference arm using an un
      adjusted significance level, consideration of the Type I familywise error is
      likely to be required. Furthermore, in trials where two or more comparisons are
      performed using the same reference arm, the comparisons are inherently
      correlated. The correlation between comparisons can be utilised to remove some of
      the conservativeness of some commonly used procedures. This article is intended
      as a practical guide that should enable calculation of significance levels that
      fully conserve Type I error and provides graphical presentation that could
      facilitate their description to non-statisticians.

PMID- 20826501
TI  - Closed-form confidence intervals for functions of the normal mean and standard
      deviation.
AB  - Confidence interval methods for a normal mean and standard deviation are well
      known and simple to apply. However, the same cannot be said for important
      functions of these parameters. These functions include the normal distribution
      percentiles, the Bland-Altman limits of agreement, the coefficient of variation
      and Cohen's effect size. We present a simple approach to this problem by using
      variance estimates recovered from confidence limits computed for the mean and
      standard deviation separately. All resulting confidence intervals have closed
      forms. Simulation results demonstrate that this approach performs very well for
      limits of agreement, coefficients of variation and their differences.

PMID- 20826502
TI  - A conditional approach for inference in multivariate age-period-cohort models.
AB  - Age-period-cohort (APC) models are used to analyse data from disease registers
      given by age and time. When data are stratified by one further variable, for
      example geographical location, multivariate APC (MAPC) models can be applied to
      identify and estimate heterogeneous time trends across the different strata. In
      such models, outcomes share a set of parameters, typically the age effects, while
      the remaining parameters may differ across strata. In this article, we propose a
      conditional approach for inference to directly model relative time trends. We
      show that in certain situations the conditional approach can handle unmeasured
      confounding so that relative risks might be estimated with higher precision.
      Furthermore, we propose an extension for data with more stratification levels.
      Maximum likelihood estimation is performed using software for multinomial
      logistic regression. The usage of smoothing splines is suggested to stabilise
      estimates of relative time trends, if necessary. We apply the methodology to
      chronic obstructive pulmonary disease mortality data in England & Wales,
      stratified by three different areas and gender.

PMID- 20826503
TI  - Thinking shrinks: decision making in psychiatry.

PMID- 20826504
TI  - 'Hikikomori': a new diagnosis or a syndrome associated with a psychiatric
      diagnosis?

PMID- 20826505
TI  - Substantial variation in transplacental transfer of chemotherapeutic agents in a
      mouse model.
AB  - OBJECTIVE: Data on the transplacental transfer of chemotherapeutic agents are
      lacking. We aimed to measure the maternofetal transfer of cytotoxic drugs in a
      mouse model. STUDY DESIGN: The transplacental transfer of doxorubicin (9 mg/kg),
      epirubicin (11 mg/kg), vinblastine (6 mg/kg), carboplatin (50 mg/kg), paclitaxel
      (10 mg/kg), and cytarabine (100 mg/kg) was tested in a C57/Bl6J mouse model.
      Ninety minutes after intravenous (IV) drug injection on gestational day 18.5,
      maternal and fetal blood were collected simultaneously. Plasma drug levels were
      determined using high performance liquid chromatography or atomic absorption
      spectrometry. RESULTS: Fetal plasma concentrations of doxorubicin, epirubicin,
      vinblastine, and cytarabine were 5.1% +/- 0.6% (n = 8), 4.8% +/- 3.8% (n = 8),
      13.8% +/- 5.8% (n = 6), and 56.7% +/- 22.6% (n = 6) of the maternal
      concentrations, respectively. Total platinum passed the mouse placenta easily
      (117.0% +/- 38.9%, n = 6). Paclitaxel could not be detected in fetal plasma
      samples (n = 6). CONCLUSIONS: Substantial variations in transplacental transfer
      were noted among the tested drugs. Current findings contribute to the
      understanding of reported pregnancy outcomes in humans.

PMID- 20826506
TI  - The RAV1 transcription factor positively regulates leaf senescence in
      Arabidopsis.
AB  - Leaf senescence is a developmentally programmed cell death process that
      constitutes the final step of leaf development and involves the extensive
      reprogramming of gene expression. Despite the importance of senescence in plants,
      the underlying regulatory mechanisms are not well understood. This study reports
      the isolation and functional analysis of RAV1, which encodes a RAV family
      transcription factor. Expression of RAV1 and its homologues is closely associated
      with leaf maturation and senescence. RAV1 mRNA increased at a later stage of leaf
      maturation and reached a maximal level early in senescence, but decreased again
      during late senescence. This profile indicates that RAV1 could play an important
      regulatory role in the early events of leaf senescence. Furthermore, constitutive
      and inducible overexpression of RAV1 caused premature leaf senescence. These data
      strongly suggest that RAV1 is sufficient to cause leaf senescence and it
      functions as a positive regulator in this process.

PMID- 20826507
TI  - A specific binding site for the prorenin propart peptide Arg10-Arg20 does not
      occur on human endothelial cells.
AB  - INTRODUCTION: We looked for novel binding sites for the human prorenin 'decoy
      peptide' sometimes called 'handle region peptide' on human endothelial cells.
      METHOD: The biotinylated peptide biotin-Acp-RIFLKRMPSIR (B-PR), an unlabelled
      peptide PR1 (RIFLKRMPSIR) and a scrambled peptide scPR1 (SRRMIFPIKLR) were
      synthesized. B-PR was added to human umbilical cord endothelial cells (HUVECs)
      maintained in serum-free medium, with or without excess unlabelled peptide or
      'scrambled' peptide as blocker. Biotin-labelled HUVEC proteins were extracted,
      the amount of bound tracer was measured, and the identity of the binding proteins
      was analysed by sodium-dodecyl-sulphate polyacrylamide gel electrophoresis (SDS
      PAGE) and by liquid chromatography coupled with tandem mass spectrometry (LC
      MS/MS). RESULTS: Biotinylated peptide bound to the HUVEC proteins with a major
      labelled band at 68,600 +/- 1503 kDa (mean +/- SEM, n = 5 runs). Unlabelled
      peptide and scrambled peptide equally displaced the labelled peptide, indicating
      that the binding was non-specific for amino acid sequence. LC-MS/MS showed that
      binding was mainly to cytoskeletal proteins. CONCLUSION: The binding of the human
      prorenin peptide R10IFLKRMPSIR20 to HUVEC proteins is not specific for amino acid
      sequence and probably involves a general peptide/protein uptake mechanism. We
      could not detect a specific prorenin propart binding site in these cells.

PMID- 20826508
TI  - Use of extracorporeal life support to support patients with acute respiratory
      distress syndrome due to H1N1/2009 influenza and other respiratory infections.
AB  - A large proportion of critically ill H1N1/2009 patients with respiratory failure
      subsequently developed ARDS and, to date, about 400 patients receiving
      extracorporeal life support (ECLS) have been accounted for globally, with a
      reported survival rate from 63% to 79%. The survival rates of patients with ARDS
      due to non-H1N1/2009 infections are similar. There is no definite evidence to
      suggest that patient outcomes are changed by ECLS, but its use is associated with
      serious short-term complications. ECLS relies on an extracorporeal circuit, with
      extracorporeal membrane oxygenation (ECMO) and pumpless interventional lung
      assist (ILA) being the two major types employed in ARDS. Both have the potential
      to correct respiratory failure and related haemodynamic instability. There are
      only a very limited number of clinical trials to test either and, although ECLS
      has been used in treating H1N1/2009 patients with ARDS with some success, it
      should only be offered in the context of clinical trials and in experienced
      centres.

PMID- 20826509
TI  - Incidence of acute myocardial infarction resulting in sudden death outside the
      hospital.
AB  - OBJECTIVE: To prospectively determine the percentage of cases of acute myocardial
      infarction (AMI) resulting in sudden death outside the hospital. METHODS: Two
      groups of patients were defined by the emergency medical services. Group A
      comprised all out-of-hospital sudden deaths in 2004 meeting the criteria for
      possible or probable AMI (n=395 among 1072 sudden death patients, ie, 37%). Group
      B comprised all in-hospital AMI in the district during the same year according to
      hospital registry records (n=731). RESULTS: The out-of-hospital sudden death rate
      due to AMI was determined by the ratio of the number of patients in group A over
      the total number of patients (A+B), and was found to be 35% (95% CI 32% to 38%).
      CONCLUSION: The estimated mortality of AMI appears to be 35% in this population.
      This figure suggests that significant improvement in the treatment of out-of
      hospital cardiac arrest is still necessary.

PMID- 20826510
TI  - Therapeutic hypothermia following out-of-hospital cardiac arrest; does it start
      in the emergency department?
AB  - BACKGROUND: The use of therapeutic hypothermia after cardiac arrest is a well
      practised treatment modality in the intensive care unit (ICU). However, recent
      evidence points to advantages in starting the cooling process as soon as possible
      after the return of spontaneous circulation (ROSC). There are no data on
      implementation of this treatment in the emergency department. METHODS: A
      telephone survey was conducted of the 233 emergency departments in the UK. The
      most senior available clinician was asked if, in cases where they have a patient
      with a ROSC after an out-of-hospital cardiac arrest, would therapeutic
      hypothermia be started in the emergency department. RESULTS: Of the 233 hospitals
      called, 230 responded, of which 35% would start cooling in the emergency
      department. Of this 35%, over half (56%) said the decision to start cooling was
      made by the emergency physician before consultation with the ICU. Also, of the
      35% who would begin cooling in the emergency department, 55% would cool only for
      ventricular fibrillation/ventricular tachycardia, 66% would monitor temperature
      centrally, and 14% would use specialised cooling equipment. CONCLUSIONS: There is
      often a delay in getting patients to ICU from the emergency department, and thus
      the decision not to start cooling in the emergency department may impact
      significantly on patient outcome. The dissemination of these data may persuade
      emergency physicians that starting treatment in the emergency department is an
      appropriate and justifiable decision that is becoming a more accepted practice
      throughout the UK.

PMID- 20826512
TI  - Clinical decision rules for acute coronary syndromes: the specifics.

PMID- 20826511
TI  - Infections in crush syndrome: a retrospective observational study after the
      Wenchuan earthquake.
AB  - OBJECTIVES: To investigate the characteristics of infections in the casualties
      with crush syndrome after the Wenchuan earthquake. METHODS: The clinical data of
      patients during their first 2 months of hospitalisation were analysed
      retrospectively. 58 crush syndrome patients were included. Demographic data,
      physical and laboratory findings, treatment and outcome were recorded. RESULTS:
      The mean age of these patients was 32.8+/-20.7 years and the average duration
      under the rubble was 23.7+/-19.3 h. Fasciotomy and amputation were performed in
      29 (50%) and 34 (58.6%) patients, respectively. Renal replacement therapies were
      administered to 47 patients (81%). Four patients died while all the others
      restored their renal function. Microbial pathogens were detected in the samples
      from 39 patients (67.2%), 26 of whom developed sepsis. The most vulnerable sites
      for infection were wounds (55.2%) and lungs (37.9%). Acinetobacter baumanii and
      Pseudomonas aeruginosa were the most common bacterial isolates from wound
      infections. 26 of 39 patients (66.7%) became infected after 48 h of admission.
      The infected group had a longer duration under the rubble (39.2 h vs 30.1 h,
      p=0.000) and more fasciotomies (61.5% vs 26.3%, p=0.012) compared with those
      without infections. Multivariate analysis indicated that duration under the
      rubble (p=0.012, OR 1.061), duration of renal impairment (p=0.015, OR 1.096) and
      fasciotomy (p=0.024, OR 5.470) were risk factors for infection. CONCLUSIONS:
      Infectious complications are common in crush syndrome. In order to improve
      patient outcomes, vigorous care and strict surveillance are required.

PMID- 20826515
TI  - An acutely swollen knee.

PMID- 20826522
TI  - Group calls on Indian government to ban "degrading" finger test after rape.

PMID- 20826523
TI  - More obesity surgery in England would save money, economic analysis shows.

PMID- 20826525
TI  - Minimal changes in environmental temperature result in a significant increase in
      energy expenditure and changes in the hormonal homeostasis in healthy adults.
AB  - OBJECTIVE: Resting energy expenditure (EE) is a major contributor to the total EE
      and thus plays an important role in body weight regulation. Adaptive
      thermogenesis is a major component of EE in rodents, but little is known on the
      effects of exposure of humans to mild and sustainable reduction in environmental
      temperature. DESIGN: To characterize the dynamic changes in continuously measured
      resting EE, substrate utilization, and hormonal axes simultaneously in response
      to mild reduction in environmental temperature, we performed a cross-over
      intervention. METHODS: Twenty-five volunteers underwent two 12-h recordings of EE
      in whole room indirect calorimeters at 24 and 19  degrees C with simultaneous
      measurement of spontaneous movements and hormonal axes. RESULTS: Exposure to 19 
      degrees C resulted in an increase in plasma and urine norepinephrine levels
      (P<0.0001), and a 5.96% (P<0.001) increase in EE without significant changes in
      spontaneous physical activity. Exposure to the lower temperature resulted in a
      significant increase in free fatty acid levels (P<0.01), fasting insulin levels
      (P<0.05), and a marginal decrease in postprandial glucose levels. A small but
      significant (P<0.002) increase in serum free thyroxine and urinary free cortisol
      (P<0.05) was observed at 19  degrees C. CONCLUSIONS: Our observations indicate
      that exposure to 19  degrees C, a mild and tolerable cold temperature, results in
      a predictable increase in EE driven by a sustained rise in catecholamine and the
      activation of counter-regulatory mechanisms.

PMID- 20826526
TI  - Causes of death among patients with multiple sclerosis.
AB  - BACKGROUND: Several studies show a high mortality risk among patients with
      multiple sclerosis (MS). OBJECTIVES: In this study, mortality and underlying
      causes of death were analysed among patients with MS diagnosed between 1964-1993
      in Finland (n = 1595). METHODS: Standardized mortality ratios (SMRs) were
      calculated for both genders. The follow-up was based on linkage to the national
      computerized Cause-of-Death Register of Statistics Finland. RESULTS: Altogether,
      464 deaths were recorded by the end of 2006. The SMR as compared with the general
      population among females was 3.4 (95% confidence interval 3.0-3.9) and among
      males 2.2 (1.9-2.6). In total, 270 patients (58%) died from MS; only one of these
      deaths occurred during the first 2 years after the MS diagnosis. Mortality was
      also increased for other natural causes of death (n = 160) in patients followed
      for more than 10 years (SMR 1.4, 1.2-1.7), with a significant increase in deaths
      from influenza (29, 6.0-85), pneumonia (4.7, 2.5-8.0) and gastrointestinal causes
      (4.4, 2.3-7.7). The SMR for violent causes was 1.2 (0.7-1.9) and for alcohol
      related deaths 0.2 (0.02-0.7). The SMR for suicides was 1.7 (0.9-2.7).
      CONCLUSIONS: The MS population has an increased disease mortality, while the
      increase in the risk of accidents and suicides is not significantly increased
      among patients with MS in Finland.

PMID- 20826527
TI  - Risk perception in natalizumab-treated multiple sclerosis patients and their
      neurologists.
AB  - BACKGROUND: Natalizumab is associated with the potentially life-threatening side
      effect progressive multifocal leukoencephalopathy (PML). Little is known about
      patients' and physicians' risk estimates and attitudes towards natalizumab
      treatment. METHODS: Consecutive natalizumab-treated patients (n = 69) and
      neurologists (n = 66) in two centres and cooperating private practices received
      an evidence-based three-page information leaflet about natalizumab-associated PML
      and an evaluation sheet. RESULTS: After reading the information, patients were
      significantly more likely than physicians to intend continuation of natalizumab
      treatment and willing to accept higher risks of PML: 49% of physicians would stop
      treatment at a PML risk of 2:10,000 or lower, while only 17% of patients would do
      so (p < 0.001). This difference could not be explained by risk calculation
      abilities or lack of understanding. Both groups overestimated natalizumab
      treatment effects. CONCLUSION: Patients had a significantly worse perception of
      multiple sclerosis as a malignant disease. We conclude that patients were willing
      to accept a higher risk of PML than neurologists. Coherent with their perception
      of risks and benefits, patients were also more willing to continue treatment.
      Open information about treatment-related risks is appreciated and might support
      shared decision making.

PMID- 20826528
TI  - Quantitative analyses link modulation of sonic hedgehog signaling to continuous
      variation in facial growth and shape.
AB  - Variation is an intrinsic feature of biological systems, yet developmental
      biology does not frequently address population-level phenomena. Sonic hedgehog
      (SHH) signaling activity in the vertebrate forebrain and face is thought to
      contribute to continuous variation in the morphology of the upper jaw, but
      despite its potential explanatory power, this idea has never been quantitatively
      assessed. Here, we test this hypothesis with an experimental design that is
      explicitly focused on the generation and measurement of variation in multivariate
      shape, tissue growth, cellular behavior and gene expression. We show that the
      majority of upper jaw shape variation can be explained by progressive changes in
      the spatial organization and mitotic activity of midfacial growth zones
      controlled by SHH signaling. In addition, nonlinearity between our treatment
      doses and phenotypic outcomes suggests that threshold effects in SHH signaling
      may play a role in variability in midfacial malformations such as
      holoprosencephaly (HPE). Together, these results provide novel insight into the
      generation of facial morphology, and demonstrate the value of quantifying
      variation for our understanding of development and disease.

PMID- 20826529
TI  - Disorganized epithelial polarity and excess trophectoderm cell fate in
      preimplantation embryos lacking E-cadherin.
AB  - The first two cell lineages in the mouse, the surface trophectoderm (TE) and
      inner cell mass (ICM), are morphologically distinguishable by E3.5, with the
      outer TE forming a polarized epithelial layer enclosing the apolar ICM. We show
      here that in mouse embryos completely lacking both maternal and zygotic E
      cadherin (cadherin 1), the normal epithelial morphology of outside cells is
      disrupted, but individual cells still initiate TE- and ICM-like fates. A larger
      proportion of cells than normal showed expression of TE markers such as Cdx2,
      suggesting that formation of an organized epithelium is not necessary for TE
      specific gene expression. Individual cells in such embryos still generated an
      apical domain that correlated with elevated Cdx2 expression. We also show that
      repolarization can occur in isolated early ICMs from both wild-type and Cdx2
      mutant embryos, indicating that Cdx2 is not required for initiating polarity. The
      results demonstrate that epithelial integrity mediated by E-cadherin is not
      required for Cdx2 expression, but is essential for the normal allocation of TE
      and ICM cells. They also show that Cdx2 expression is strongly linked to apical
      membrane polarization.

PMID- 20826531
TI  - The absence of Prep1 causes p53-dependent apoptosis of mouse pluripotent epiblast
      cells.
AB  - Disruption of mouse Prep1, which codes for a homeodomain transcription factor,
      leads to embryonic lethality during post-implantation stages. Prep1(-/-) embryos
      stop developing after implantation and before anterior visceral endoderm (AVE)
      formation. In Prep1(-/-) embryos at E6.5 (onset of gastrulation), the AVE is
      absent and the proliferating extra-embryonic ectoderm and epiblast, marked by
      Bmp4 and Oct4, respectively, are reduced in size. At E.7.5, Prep1(-/-) embryos
      are small and very delayed, showing no evidence of primitive streak or of
      differentiated embryonic lineages. Bmp4 is expressed residually, while the
      reduced number of Oct4-positive cells is constant up to E8.5. At E6.5, Prep1(-/-)
      embryos retain a normal mitotic index but show a major increase in cleaved
      caspase 3 and TUNEL staining, indicating apoptosis. Therefore, the mouse embryo
      requires Prep1 when undergoing maximal expansion in cell number. Indeed, the
      phenotype is partially rescued in a p53(-/-), but not in a p16(-/-), background.
      Apoptosis is probably due to DNA damage as Atm downregulation exacerbates the
      phenotype. Despite this early lethal phenotype, Prep1 is not essential for ES
      cell establishment. A differential embryonic expression pattern underscores the
      unique function of Prep1 within the Meis-Prep family.

PMID- 20826530
TI  - zif-1 translational repression defines a second, mutually exclusive OMA function
      in germline transcriptional repression.
AB  - Specification of primordial germ cells requires global repression of
      transcription. In C. elegans, primordial germ cells are generated through four
      rounds of asymmetric divisions, starting from the zygote P0, each producing a
      transcriptionally repressed germline blastomere (P1-P4). Repression in P2-P4
      requires PIE-1, which is provided maternally in oocytes and segregated to all
      germline blastomeres. We have shown previously that OMA-1 and OMA-2 repress
      global transcription in P0 and P1 by sequestering TAF-4, an essential component
      of TFIID. Soon after the first mitotic cycle, OMA proteins undergo
      developmentally regulated degradation. Here, we show that OMA proteins also
      repress transcription in P2-P4 indirectly, through a completely different
      mechanism that operates in oocytes. OMA proteins bind to both the 3' UTR of the
      zif-1 transcript and the eIF4E-binding protein, SPN-2, repressing translation of
      zif-1 mRNA in oocytes. zif-1 encodes the substrate-binding subunit of the E3
      ligase for PIE-1 degradation. Inhibition of zif-1 translation in oocytes ensures
      high PIE-1 levels in oocytes and germline blastomeres. The two OMA protein
      functions are strictly regulated in both space and time by MBK-2, a kinase
      activated following fertilization. Phosphorylation by MBK-2 facilitates the
      binding of OMA proteins to TAF-4 and simultaneously inactivates their function in
      repressing zif-1 translation. Phosphorylation of OMA proteins displaces SPN-2
      from the zif-1 3' UTR, releasing translational repression. We propose that MBK-2
      phosphorylation serves as a developmental switch, converting OMA proteins from
      specific translational repressors in oocytes to global transcriptional repressors
      in embryos, together effectively repressing transcription in all germline
      blastomeres.

PMID- 20826532
TI  - Generation of distinct signaling modes via diversification of the Egfr ligand
      processing cassette.
AB  - Egfr ligand processing in Drosophila involves trafficking of the ligand precursor
      by the chaperone Star from the endoplasmic reticulum (ER) to a secretory
      compartment, where the precursor is cleaved by the intramembrane protease
      Rhomboid. Some of the Drosophila Rhomboids also reside in the ER, where they
      attenuate signaling by premature cleavage of Star. The genome of the flour beetle
      Tribolium castaneum contains a single gene for each of the ligand-processing
      components, providing an opportunity to assess the regulation and impact of a
      simplified ligand-processing cassette. We find that the central features of
      ligand retention, trafficking by the chaperone and cleavage by Rhomboid have been
      conserved. The single Rhomboid is localized to both ER and secretory
      compartments. However, we show that Tribolium Star is refractive to Rhomboid
      cleavage. Consequently, this ligand-processing system effectively mediates long
      range Egfr activation in the Tribolium embryonic ventral ectoderm, despite ER
      localization of Rhomboid. Diversification of the Egfr signaling pathway appears
      to have coupled gene duplication events with modulation of the biochemical
      properties and subcellular localization patterns of Rhomboid proteases and their
      substrates.

PMID- 20826533
TI  - A role for PDGF signaling in expansion of the extra-embryonic endoderm lineage of
      the mouse blastocyst.
AB  - The inner cell mass (ICM) of the implanting mammalian blastocyst comprises two
      lineages: the pluripotent epiblast (EPI) and primitive endoderm (PrE). We have
      identified platelet-derived growth factor receptor alpha (PDGFRalpha) as an early
      marker of the PrE lineage and its derivatives in both mouse embryos and ex vivo
      paradigms of extra-embryonic endoderm (ExEn). By combining live imaging of
      embryos and embryo-derived stem cells expressing a histone H2B-GFP fusion
      reporter under the control of Pdgfra regulatory elements with the analysis of
      lineage-specific markers, we found that Pdgfra expression coincides with that of
      GATA6, the earliest expressed transcriptional regulator of the PrE lineage. We
      show that GATA6 is required for the activation of Pdgfra expression. Using
      pharmacological inhibition and genetic inactivation we addressed the role of the
      PDGF pathway in the PrE lineage. Our results demonstrate that PDGF signaling is
      essential for the establishment, and plays a role in the proliferation, of XEN
      cells, which are isolated from mouse blastocyst stage embryos and represent the
      PrE lineage. Implanting Pdgfra mutant blastocysts exhibited a reduced number of
      PrE cells, an effect that was exacerbated by delaying implantation. Surprisingly,
      we also noted an increase in the number of EPI cells in implantation-delayed
      Pdgfra-null mutants. Taken together, our data suggest a role for PDGF signaling
      in the expansion of the ExEn lineage. Our observations also uncover a possible
      role for the PrE in regulating the size of the pluripotent EPI compartment.

PMID- 20826534
TI  - Planar cell polarity: the orientation of larval denticles in Drosophila appears
      to depend on gradients of Dachsous and Fat.
AB  - The larval ventral belts of Drosophila consist of six to seven rows of denticles
      that are oriented, some pointing forwards, some backwards. We present evidence
      that denticle orientation is determined almost entirely by Dachsous and Fat, one
      of two planar cell polarity systems. If we change the distribution of Dachsous we
      can alter the polarity of denticles. We suggest that the orientation of the
      individual denticle rows, in both the anterior compartment (which mostly point
      backwards) and the posterior compartment (which point forwards), is determined by
      the opposing slopes of a Dachsous/Fat gradient. We show, by altering the
      concentration gradients of Dachsous during development, that we can change the
      polarity of the denticles made by larval cells as they progress between the first
      and third larval instars without mitosis.

PMID- 20826536
TI  - Prostaglandin F2alpha (PGF2alpha) stimulates PTGS2 expression and PGF2alpha
      synthesis through NFKB activation via reactive oxygen species in the corpus
      luteum of pseudopregnant rats.
AB  - This study was undertaken to investigate how prostaglandin F(2alpha)
      (PGF(2alpha)) increases PGF(2alpha) synthesis and PTGS2 expression in the corpus
      luteum of pseudopregnant rats. We further investigated the molecular mechanism by
      which PGF(2alpha) stimulates PTGS2 expression. PGF(2alpha) (3 mg/kg) or phosphate
      buffer as a control was injected s.c. on day 7 of pseudopregnancy. Ptgs2 mRNA
      expression and PGF(2alpha) concentrations in the corpus luteum were measured at
      2, 6, and 24 h after PGF(2alpha) injection. PGF(2alpha) significantly increased
      Ptgs2 mRNA expression at 2 h and luteal PGF(2alpha) concentrations at 24 h.
      PGF(2alpha) significantly decreased serum progesterone levels at all of the times
      studied. Simultaneous administration of a selective PTGS2 inhibitor (NS-398, 10
      mg/kg) completely abolished the increase in luteal PGF(2alpha) concentrations
      induced by PGF(2alpha). PGF(2alpha) increased NFKB p65 protein expression in the
      nucleus of luteal cells 30 min after PGF(2alpha) injection, and electrophoretic
      mobility shift assay revealed that PGF(2alpha) increased binding activities of
      NFKB to the NFKB consensus sequence of the Ptgs2 gene promoter. Simultaneous
      administration of both superoxide dismutase and catalase to scavenge reactive
      oxygen species (ROS) inhibited the increases of nuclear NFKB p65 protein
      expression, lipid peroxide levels, and Ptgs2 mRNA expression induced by
      PGF(2alpha). In conclusion, PGF(2alpha) stimulates Ptgs2 mRNA expression and
      PGF(2alpha) synthesis through NFKB activation via ROS in the corpus luteum of
      pseudopregnant rats.

PMID- 20826535
TI  - Preaxial polydactyly: interactions among ETV, TWIST1 and HAND2 control anterior
      posterior patterning of the limb.
AB  - Preaxial polydactyly (PPD) is a common limb-associated birth defect characterized
      by extra digit(s) in the anterior autopod. It often results from ectopic sonic
      hedgehog (Shh) expression in the anterior limb bud. Although several
      transcription factors are known to restrict Shh expression to the posterior limb
      bud, how they function together remains unclear. Here we provide evidence from
      mouse conditional knockout limb buds that the bHLH family transcription factor
      gene Twist1 is required to inhibit Shh expression in the anterior limb bud
      mesenchyme. More importantly, we uncovered genetic synergism between Twist1 and
      the ETS family transcription factor genes Etv4 and Etv5 (collectively Etv), which
      also inhibit Shh expression. Biochemical data suggest that this genetic
      interaction is a result of direct association between TWIST1 and ETV proteins.
      Previous studies have shown that TWIST1 functions by forming homodimers or
      heterodimers with other bHLH factors including HAND2, a key positive regulator of
      Shh expression. We found that the PPD phenotype observed in Etv mutants is
      suppressed by a mutation in Hand2, indicative of genetic antagonism. Furthermore,
      overexpression of ETV proteins influences the dimerization of these bHLH factors.
      Together, our data suggest that through biochemical interactions, the Shh
      expression regulators ETV, TWIST1 and HAND2 attain a precise balance to establish
      anterior-posterior patterning of the limb.

PMID- 20826537
TI  - Polyunsaturated fatty acids modulate prostaglandin synthesis by ovine amnion
      cells in vitro.
AB  - Diets or supplements high in n-3 and n-6 polyunsaturated fatty acids (PUFAs) have
      been shown to influence the timing of parturition. PUFAs are substrates for
      prostaglandin (PG) synthesis, and PGs play central roles in parturition. Hence,
      the effects of altering PUFA composition may be mediated through alterations in
      the type and relative quantities of PGs synthesised. Therefore, we have
      investigated the effects of a range of n-3 and n-6 PUFAs in vitro on PG synthesis
      by amnion cells of late gestation ewes. The n-6 PUFA, arachidonic acid (20:4, n
      6), increased synthesis of two-series PGs. Degree of stimulation induced by the n
      6 PUFAs was dependent on the position of the PUFA in the PG synthetic pathway,
      i.e. PG production of the two-series (principally prostaglandin E(2):PGE(2))
      increased progressively with longer chain PUFAs. Effects of n-3 PUFAs on output
      of PGE(2) were more modest and variable. The two shorter chain n-3 PUFAs, alpha
      linolenic acid (18:3, n-3) and stearidonic acid (18:4, n-3), induced a small but
      significant increase in PGE(2) output, while the longest chain n-3 PUFA
      docosahexaenoic acid (22:6, n-3) inhibited PGE(2) synthesis. Dihomo-gamma
      linolenic acid (20:3, n-6), the PUFA substrate for synthesis of one-series PGs,
      induced an increase in PGE(1) generation and a decrease in PGE(2) and PGE(3)
      outputs. Hence, we have demonstrated that PUFA supplementation of ovine amnion
      cells in vitro affects the type and quantity of PGs synthesised.

PMID- 20826538
TI  - Epidermal growth factor receptor kinase activity is required for gap junction
      closure and for part of the decrease in ovarian follicle cGMP in response to LH.
AB  - The meiotic cell cycle in mouse oocytes is arrested in prophase, and then
      restarted when LH acts on the surrounding granulosa cells. The granulosa cells
      keep meiosis arrested by providing a source of cGMP that diffuses into the oocyte
      through gap junctions, and LH restarts the cell cycle by closing the junctions
      and by decreasing granulosa cell cGMP, thus lowering oocyte cGMP. Epidermal
      growth factor receptor (EGFR) activation is an essential step in triggering LH
      induced meiotic resumption, but its relationship to the cGMP decrease in the
      follicle is incompletely understood, and its possible function in causing gap
      junction closure has not been investigated. Here, we use EGFR agonists
      (epiregulin and amphiregulin) and an EGFR kinase inhibitor (AG1478) to study the
      function of the EGFR in the signaling pathways leading to the release of oocytes
      from prophase arrest. Our results indicate that the EGFR kinase contributes to LH
      induced meiotic resumption in two different ways. First, it is required for gap
      junction closure. Second, it is required for an essential component of the
      decrease in follicle cGMP. Our data show that the EGFR kinase-dependent component
      of the cGMP decrease is required for LH-induced meiotic resumption, but they also
      indicate that an as yet unidentified pathway accounts for a large part of the
      cGMP decrease.

PMID- 20826539
TI  - Naive and activated T cells display differential responsiveness to TL1A that
      affects Th17 generation, maintenance, and proliferation.
AB  - Tumor necrosis factor (TNF)-like cytokine (TL1A) is a T-cell costimulator that
      bolsters cytokine-induced activation through death receptor 3 (DR3). To explore
      the relationship between T-cell activation and TL1A responsiveness, flow
      cytometry profiled DR3 expression in resting and activated T cells. In human
      CD4(+) T cells, DR3 was induced rapidly following activation and expressed
      prominently by interleukin (IL)-17-secreting T cells (Th17). Splenic T cells from
      wild-type and DR3-deficient mice showed that TL1A activation of DR3 inhibits Th17
      generation (81 +/- 2.6% at 100 ng/ml TL1A) from naive T cells. This response was
      not associated with suppression of T-cell proliferation. Using neutralizing
      antibodies or T cells derived from genetically modified mice, TL1A inhibition of
      Th17 development was found to be independent of IL-2, IL-27, gammaIFN, IFNAR1,
      and STAT1. Under suboptimal TCR activation, TL1A continued to block IL-17A
      secretion, however, the reduced threshold of TCR engagement was now linked with
      an increase in TL1A-driven proliferation. In contrast, fully committed Th17 cells
      displayed an altered TL1A responsiveness and in the absence of TCR costimulation
      supported the maintenance of T cell IL-17A expression. Consequently, TL1A
      orchestrates unique outcomes in naive and effector T-helper cells, which may
      affect the proliferation, differentiation and maintenance of Th17 cells in
      peripheral compartments and inflamed tissues.

PMID- 20826540
TI  - Hepatic response to oxidative injury in long-lived Ames dwarf mice.
AB  - Multiple stress resistance pathways were evaluated in the liver of Ames dwarf
      mice before and after exposure to the oxidative toxin diquat, seeking clues to
      the exceptional longevity conferred by this mutation. Before diquat treatment,
      Ames dwarf mice, compared with nonmutant littermate controls, had 2- to 6-fold
      higher levels of expression of mRNAs for immediate early genes and 2- to 5-fold
      higher levels of mRNAs for genes dependent on the transcription factor Nrf2.
      Diquat led to a 2-fold increase in phosphorylation of the stress kinase ERK in
      control (but not Ames dwarf) mice and to a 50% increase in phosphorylation of the
      kinase JNK2 in Ames dwarf (but not control) mice. Diquat induction of Nrf2
      protein was higher in dwarf mice than in controls. Of 6 Nrf2-responsive genes
      evaluated, 4 (HMOX, NQO-1, MT-1, and MT-2) remained 2- to 10-fold lower in
      control than in dwarf liver after diquat, and the other 2 (GCLM and TXNRD)
      reached levels already seen in dwarf liver at baseline. Thus, livers of Ames
      dwarf mice differ systematically from controls in multiple stress resistance
      pathways before and after exposure to diquat, suggesting mechanisms for stress
      resistance and extended longevity in Ames dwarf mice.

PMID- 20826542
TI  - A new approach to analyze cell surface protein complexes reveals specific
      heterodimeric metabotropic glutamate receptors.
AB  - G-protein-coupled receptors (GPCRs) can form heteromeric complexes. Herein, we
      describe a new approach to test the heteromerization of 2 receptors, or 2
      receptor subunits, and to study the stoichiometry of the resulting complexes. As
      a proof-of-concept study, we investigated whether metabotropic glutamate
      receptors (mGluRs), in addition to being well-known homodimers, can form
      heteromers. To that aim, we combine the benefits of time-resolved fluorescence
      resonance energy transfer (trFRET) with the specific, cell-surface labeling of
      SNAP- and CLIP-tagged rat mGluR subunits, expressed in a mammalian cell line.
      First, we show that mGlu2 and mGlu4 subunits (but not mGlu2 and mGlu1) can
      heteromerize. Moreover, our trFRET data are consistent with mGluR subunits
      forming strict homodimeric receptors on single expression, and a combination of
      strict heterodimeric and strict homodimeric receptors on coexpression. Second, a
      comprehensive analysis reveals that from the 21 possible pairs of 2 mGluR
      subunits out of 7 subtypes (mGlu1 to 8, but not 6), only 11 are able to form
      heterodimers. These findings were further validated by biochemical and functional
      complementation studies. In addition to describing a new method to analyze cell
      surface receptor complexes, our data reveal a new level of complexity within the
      mGluR family.

PMID- 20826541
TI  - Toll-like receptor 4 mediates lipopolysaccharide-induced muscle catabolism via
      coordinate activation of ubiquitin-proteasome and autophagy-lysosome pathways.
AB  - Cachectic muscle wasting is a frequent complication of many inflammatory
      conditions, due primarily to excessive muscle catabolism. However, the
      pathogenesis and intervention strategies against it remain to be established.
      Here, we tested the hypothesis that Toll-like receptor 4 (TLR4) is a master
      regulator of inflammatory muscle catabolism. We demonstrate that TLR4 activation
      by lipopolysaccharide (LPS) induces C2C12 myotube atrophy via up-regulating
      autophagosome formation and the expression of ubiquitin ligase atrogin-1/MAFbx
      and MuRF1. TLR4-mediated activation of p38 MAPK is necessary and sufficient for
      the up-regulation of atrogin1/MAFbx and autophagosomes, resulting in myotube
      atrophy. Similarly, LPS up-regulates muscle autophagosome formation and ubiquitin
      ligase expression in mice. Importantly, autophagy inhibitor 3-methyladenine
      completely abolishes LPS-induced muscle proteolysis, while proteasome inhibitor
      lactacystin partially blocks it. Furthermore, TLR4 knockout or p38 MAPK
      inhibition abolishes LPS-induced muscle proteolysis. Thus, TLR4 mediates LPS
      induced muscle catabolism via coordinate activation of the ubiquitin-proteasome
      and the autophagy-lysosomal pathways.

PMID- 20826543
TI  - Immunological regulation of metabolism--a novel quintessential role for the
      immune system in health and disease.
AB  - The hypothalamus-pituitary-thyroid (HPT) axis is an integrated hormone network
      that is essential for maintaining metabolic homeostasis. It has long been known
      that thyroid stimulating hormone (TSH), a central component of the HPT axis, can
      be made by cells of the immune system; however, the role of immune system TSH
      remains enigmatic and most studies have viewed it as a cytokine used to regulate
      immune function. Recent studies now indicate that immune system-derived TSH, in
      particular, a splice variant of TSHbeta that is preferentially made by cells of
      the immune system, is produced by a subset of hematopoietic cells that traffic to
      the thyroid. On the basis of these and other findings, we propose the novel
      hypothesis that the immune system is an active participant in the regulation of
      basal metabolism. We further speculate that this process plays a critical role
      during acute and chronic infections and that it contributes to a wide range of
      chronic inflammatory conditions with links to thyroid dysregulation. This
      hypothesis, which is amenable to empirical analysis, defines a previously unknown
      role for the immune system in health and disease, and it provides a dynamic
      connection between immune-endocrine interactions at the organismic level.

PMID- 20826544
TI  - Physiological loading of joints prevents cartilage degradation through CITED2.
AB  - Both overuse and disuse of joints up-regulate matrix metalloproteinases (MMPs) in
      articular cartilage and cause tissue degradation; however, moderate
      (physiological) loading maintains cartilage integrity. Here, we test whether
      CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2), a
      mechanosensitive transcriptional coregulator, mediates this chondroprotective
      effect of moderate mechanical loading. In vivo, hind-limb immobilization of
      Sprague-Dawley rats up-regulates MMP-1 and causes rapid, histologically
      detectable articular cartilage degradation. One hour of daily passive joint
      motion prevents these changes and up-regulates articular cartilage CITED2. In
      vitro, moderate (2.5 MPa, 1 Hz) intermittent hydrostatic pressure (IHP) treatment
      suppresses basal MMP-1 expression and up-regulates CITED2 in human chondrocytes,
      whereas high IHP (10 MPa) down-regulates CITED2 and increases MMP-1. Competitive
      binding and transcription assays demonstrate that CITED2 suppresses MMP-1
      expression by competing with MMP transactivator, Ets-1 for its coactivator p300.
      Furthermore, CITED2 up-regulation in vitro requires the p38delta isoform, which
      is specifically phosphorylated by moderate IHP. Together, these studies identify
      a novel regulatory pathway involving CITED2 and p38delta, which may be critical
      for the maintenance of articular cartilage integrity under normal physical
      activity levels.

PMID- 20826546
TI  - Prolactin receptor-integrin cross-talk mediated by SIRPalpha in breast cancer
      cells.
AB  - The hormone prolactin (PRL) contributes to the pathogenesis of breast cancer in
      part through its activation of Janus-activated kinase 2 (Jak2)/signal transducer
      and activator of transcription 5 (Stat5), a PRL receptor (PRLr)-associated
      pathway dependent on cross-talk signaling from integrins. It remains unclear,
      however, how this cross-talk is mediated. Following PRL stimulation, we show that
      a complex between the transmembrane glycoprotein signal regulatory protein-alpha
      (SIRPalpha) and the PRLr, beta(1) integrin, and Jak2 in estrogen receptor
      positive (ER(+)) and ER(-) breast cancer cells is formed. Overexpression of
      SIRPalpha in the absence of collagen 1 significantly decreased PRL-induced gene
      expression, phosphorylation of PRLr-associated signaling proteins, and PRL
      stimulated proliferation and soft agar colony formation. In contrast,
      overexpression of SIRPalpha in the presence of collagen 1 increased PRL-induced
      gene expression; phosphorylation of Jak2, Stat5, and Erk; and PRL-stimulated cell
      growth. Interestingly, overexpression of a tyrosine-deficient SIRPalpha
      (SIRPalpha-4YF) prevented the signaling and phenotypic effects mediated by wild
      type SIRPalpha. Furthermore, overexpression of a phosphatase-defective mutant of
      Shp-2 or pharmacologic inhibition of Shp-2 produced effects comparable with that
      of SIRPalpha-4YF. However, the tyrosine phosphorylation of SIRPalpha was
      unaffected in the presence or absence of collagen 1. These data suggest that
      SIRPalpha modulates PRLr-associated signaling as a function of integrin occupancy
      predominantly through the alteration of Shp-2 activity. This PRLr-SIRPalpha
      integrin complex may therefore provide a basis for integrin-PRLr cross-talk and
      contribute to the biology of breast cancer.

PMID- 20826545
TI  - Embelin suppresses osteoclastogenesis induced by receptor activator of NF-kappaB
      ligand and tumor cells in vitro through inhibition of the NF-kappaB cell
      signaling pathway.
AB  - Most patients with cancer die not because of the tumor in the primary site, but
      because it has spread to other sites. Common tumors, such as breast, multiple
      myeloma, and prostate tumors, frequently metastasize to the bone. It is now well
      recognized that osteoclasts are responsible for the osteolysis observed in bone
      metastases of the tumor. Receptor activator of NF-kappaB ligand (RANKL), a member
      of the tumor necrosis factor superfamily and an activator of the NF-kappaB
      signaling pathway, has emerged as a major mediator of bone loss, commonly
      associated with cancer and other chronic inflammatory diseases. Embelin (2,5
      dihydroxy-3-undecyl-1,4-benzoquinone), derived from the Ayurvedic medicinal plant
      Embelia ribes, has been shown to bind and inhibit X-linked inhibitor of apoptosis
      protein and inhibit inflammatory pathways. We investigated whether embelin could
      inhibit osteoclastogenesis-associated bone loss induced by RANKL and by tumor
      cells in vitro. We found that embelin suppressed the RANKL-induced
      differentiation of monocytes into osteoclasts. This benzoquinone also suppressed
      the osteoclastogenesis induced by multiple myeloma and by breast cancer cells.
      This effect of embelin correlated with the suppression of NF-kappaB activation
      and inhibition of IkappaBalpha phosphorylation and IkappaBalpha degradation.
      Inhibition of IkappaBalpha phosphorylation was due to the inhibition of
      IkappaBalpha kinase (IKK) activation. Furthermore, by using an inhibitor of the
      IKKgamma or NF-kappaB essential modulator (NEMO), the regulatory component of the
      IKK complex, we showed that the NF-kappaB signaling pathway is mandatory for RAW
      264.7 cell differentiation into osteoclasts. Thus, embelin, an inhibitor of RANKL
      induced NF-kappaB activation has great potential as a therapeutic agent for
      osteoporosis and cancer-linked bone loss.

PMID- 20826547
TI  - Mechanism-based inactivation of human CYP2E1 by diethyldithocarbamate.
AB  - Although the ability of disulfiram to inactivate CYP2E1 has been known for more
      than 20 years, the mechanism has not yet been elucidated. A metabolite of
      disulfiram, diethyldithocarbamate (DDC), is converted by CYP2E1 to a reactive
      intermediate that subsequently inactivates the protein, leading to mechanism
      based inactivation. Mass spectral analysis of the inactivated human 2E1 protein
      demonstrates that the inactivation is due to the formation of an adduct of the
      reactive metabolite of DDC with the apoprotein. These data, along with mass
      spectral analysis of a reactive intermediate trapped with GSH, indicate the
      involvement of a reactive intermediate with a molecular mass of 116 Da. Our
      results suggest that this binding involves formation of a disulfide bond with one
      of the eight cysteines in CYP2E1. The inactivation of wild-type CYP2E1 as well as
      two of its polymorphic mutants, CYP2E1*2 and CYP2E1*4, was also investigated. For
      wild-type CYP2E1, the K(I) was 12.2 MUM and the k(inact) was 0.02 min(-1). The
      K(I) values for the two polymorphic mutants were 227.6 and 12.4 MUM for CYP2E1.2
      and CYP2E1.4, and the k(inact) values were 0.0061 and 0.0187 min(-1),
      respectively. These data indicate that DDC is a much less efficient inactivator
      of CYP2E1.2 than it is of either the wild-type or the CYP2E1.4 variant.

PMID- 20826550
TI  - Transfusions increase with nationally driven reimbursement changes of
      erythropoiesis stimulating agents for chemotherapy-induced anemia.
AB  - BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) issued a
      national coverage determination (NCD) in July 2007, which imposed restrictions on
      the reimbursement of ESAs for Medicare and Medicaid beneficiaries. Since a
      majority of our patients are Medicare or Medicaid beneficiaries, we changed our
      clinical practice regarding the use of erythropoiesis stimulating agents (ESAs)
      to coincide with the NCD's reimbursement restriction. OBJECTIVE: To evaluate the
      number of transfusions in patients diagnosed with chemotherapy-induced anemia
      (CIA) receiving ESAs before and after the clinical practice was changed at the
      University of Illinois Medical Center (UIMC). METHODS: The medical records of all
      adult patients diagnosed with a nonmyeloid malignancy and CIA who received an ESA
      between July 2006 and June 2008 at the UIMC were evaluated. The patients were
      divided into two groups: patients in receipt of ESAs BEFORE (group 1) and AFTER
      (group 2). The number of transfusions, the response rates to chemotherapy and
      ESAs therapy, and overall survival were compared. RESULTS: Medical records for
      110 patients were reviewed. More transfusions were given to patients AFTER we
      implemented the change in clinical practice (BEFORE 18 transfusions vs. AFTER 52
      transfusions, p = 0.004). More patients responded to ESA therapy AFTER we
      implemented the change (67% vs. 83%, p = NS). The treatment response to
      chemotherapy and overall survival were similar between the two groups.
      CONCLUSION: The primary goal of reducing the number of transfusions in patients
      with CIA by administering ESAs cannot be met when clinical practice coincides
      with the NCD.

PMID- 20826551
TI  - Effect of cesium radioisotope on humoral immune status in Ukrainian children with
      clinical symptoms of irritable bowel syndrome related to Chernobyl disaster.
AB  - The aim of this study is to determine humoral immune status in Ukrainian children
      with clinical symptoms of irritable bowel syndrome 23 years after the Chernobyl
      disaster. METHOD AND MATERIAL: The test population consisted of 95 participants:
      75 rural patients aged 4-18, who lived in a contaminated area exposed to natural
      environmental radiation (falling under three groups) and 20 healthy urban
      participants from Kiev aged 5-15 as a control group. Internal radiation activity
      has been measured by gamma-ray spectrometry. B-lymphocytes population was
      analyzed with monoclonal antibody against antigen CD22(+). Serum immunoglobulins
      were evaluated by enzyme-linked immunosorbent assay (ELISA) method. p < 0.05 was
      considered significant. RESULT: The percentage of CD22(+) in study groups is
      increased significantly in comparison to control group at p < 0.05. Reduced serum
      immunoglobulins levels have developed in the majority of the participants.
      CONCLUSION: Humoral immune status of study groups with clinical symptom of
      irritable bowel syndrome residing in a contaminated area has changed.

PMID- 20826552
TI  - Effects on prolongation of Bazett's corrected QT interval of seven second
      generation antipsychotics in the treatment of schizophrenia: a meta-analysis.
AB  - The use of second-generation antipsychotics (SGAs) for the treatment of
      schizophrenia has surged worldwide. Amisulpride, aripiprazole, olanzapine,
      quetiapine, risperidone, sertindole and ziprasidone have now been commonly
      prescribed. Their effects on QT interval differ but evidence remains sparse and
      mostly inconclusive. Since prolongation of heart-rate corrected QT interval has
      been implicated as an useful surrogate marker to predict drug-related cardiac
      mortality and pro-arrhythmic potentials, it is timely and necessary to compare
      the effects of Bazett's corrected QT interval (QT(Bc)) prolongation for the
      commonly prescribed SGAs. A meta-analysis was conducted according to suggestions
      by the Quality of Reporting of Meta-analysis group with literature identified
      using various databases and augmented with hand-searching to assess the magnitude
      and risk on QT(Bc) prolongation by these seven SGAs for treatments in adult
      subjects with schizophrenia. Because of incomplete QT(Bc) data reporting,
      quetiapine could not be assessed by the meta-analytical approach in this study.
      Aripiprazole was the only SGA associated with both statistically significant
      lower risk and mean change in QT(Bc), with sertindole giving a statistically
      significant worsening effect on mean QT(Bc). Other analyses did not demonstrate
      any statistically significant pooled effects for the studied SGAs, neither on the
      magnitude over mean or mean change, nor the risk on QT(Bc) prolongation.

PMID- 20826548
TI  - Nuclear lamins.
AB  - The nuclear lamins are type V intermediate filament proteins that are critically
      important for the structural properties of the nucleus. In addition, they are
      involved in the regulation of numerous nuclear processes, including DNA
      replication, transcription and chromatin organization. The developmentally
      regulated expression of lamins suggests that they are involved in cellular
      differentiation. Their assembly dynamic properties throughout the cell cycle,
      particularly in mitosis, are influenced by posttranslational modifications.
      Lamins may regulate nuclear functions by direct interactions with chromatin and
      determining the spatial organization of chromosomes within the nuclear space.
      They may also regulate chromatin functions by interacting with factors that
      epigenetically modify the chromatin or directly regulate replication or
      transcription.

PMID- 20826549
TI  - Apoptosis and autophagy: decoding calcium signals that mediate life or death.
AB  - Calcium is a versatile and dynamic 2nd messenger that is essential for the
      survival of all higher organisms. In cells that undergo activation or excitation,
      calcium is released from the endoplasmic/sarcoplasmic reticulum to activate
      calcium-dependent kinases and phosphatases, thereby regulating numerous cellular
      processes; for example, apoptosis and autophagy. In the case of apoptosis,
      endogenous ligands or pharmacological agents induce prolonged cytosolic calcium
      elevation, which in turn leads to cell death. In contrast, there is now evidence
      that calcium regulates autophagy by several mechanisms, and these may be
      important for maintaining cell survival. Here we summarize what is known about
      how calcium regulates these life and death decisions. We pay particular attention
      to pathways that have been described in lymphocytes and cardiomyocytes, as these
      systems provide optimal models for understanding calcium signaling in the context
      of normal cell physiology.

PMID- 20826553
TI  - Variation in GNB3 predicts response and adverse reactions to antidepressants.
AB  - There is substantial inter-individual variation in response and adverse reactions
      to antidepressants, and genetic variation may, in part, explain these
      differences. GNB3 encodes the beta3 subunit of the G protein complex, which is
      involved in the downstream signalling cascade following monoamine receptor
      activation. A functional polymorphism in this gene (C825T) has been associated
      with response to antidepressants. Several lines of evidence suggest that GNB3
      moderates improvement in the neurovegetative symptoms of depression (such as
      sleep and appetite) and related adverse reactions independently of change in core
      mood symptoms. We here report analysis of data from GENDEP, a part-randomized
      pharmacogenomic trial, on the outcome of 811 subjects with major depression
      undergoing treatment with either escitalopram or nortriptyline in which the C825T
      SNP and three further SNPs in GNB3 were genotyped. The TT genotype was
      significantly associated with a superior response to nortriptyline and these
      effects were specific to improvements in neurovegetative symptoms. In addition,
      the same genotype predicted fewer incidents of treatment-emergent insomnia and
      greater weight gain on the same drug. Our results are consistent with previous
      associations with GNB3 and emphasize the importance of signalling genes in
      antidepressant response.

PMID- 20826554
TI  - Instability of the ecstasy market and a new kid on the block: mephedrone.
AB  - Recently, several reports have indicated instability of the ecstasy market in the
      Netherlands and other EU countries. In the current study, we demonstrate this
      instability in the Netherlands, showing a decrease of ecstasy tablets containing
      3,4-methylenedioxymetamphetamine (MDMA) by more than 50% in 2009. In addition, we
      describe a partial replacement of MDMA in tablets sold as ecstasy by a previously
      unseen substance, mephedrone (or 4-methylmethcathinone). Mephedrone was
      quantified and ecstasy tablets contained between 96 and 155 mg of this new
      compound. So far, no studies about mephedrone's effects have been published. For
      this study, we gathered information on the acute subjective effects of mephedrone
      from 70 regular ecstasy users. Overall, the majority of users considered the
      effects enjoyable. Mephedrone seemed to evoke effects similar to other
      amphetamine type psychostimulants, including MDMA. In contrast to MDMA, however,
      mephedrone induced strong feelings of craving in most users. If the unstable
      ecstasy market situation persists, the potential of mephedrone to substitute for
      MDMA might be substantial. Mephedrone, sold as ecstasy, is therefore likely to be
      a valid cause for health concern.

PMID- 20826555
TI  - Mycoplasma hominis mediastinitis after acute aortic dissection repair.
AB  - We report a case of ascending aortic graft infection by an atypical bacteria,
      Mycoplasma hominis, with mediastinitis, a dreaded complication after cardiac
      surgery. A 55-year-old patient underwent ascending aorta replacement for acute
      type A dissection. He developed sternal instability and purulent discharge,
      requiring sternal wire removal and debridement. Cultures were initially sterile,
      but showed M. hominis infection after a significant delay and in specific culture
      media. The patient was treated with doxycycline and moxifloxacine. Cultures
      became negative and the sternum was closed on the 28th postoperative day after
      the first debridement. Recovery was favorable, with no signs of infection.
      Antibiotics were continued for one year. The patient is still asymptomatic 16
      months after antibiotic interruption. Atypical organisms should be considered in
      the differential diagnosis of acute mediastinitis of unknown etiology after
      routine microbiological investigations.

PMID- 20826556
TI  - The natural bifurcating internal thoracic artery graft: another technique for
      bypassing two vessels with one conduit.
AB  - We present our reproducible technique of achieving two bypasses from selected
      pedicled internal thoracic arteries. We feel that awareness of this technical
      modification is to the benefit of patients.

PMID- 20826557
TI  - Cardiopulmonary bypass line sternal wrapping: technical tips.
AB  - Cardiopulmonary bypass line sternal wrapping (SW) is a new approach to sternal
      care which avoids bone wax and offers mechanical protection and a shield from
      bacterial contamination, with beneficial effects on sternal healing. Since its
      introduction in February 2008, the technique has undergone some developments: it
      is possible to harvest internal thoracic arteries with SW in place and its
      haemostatic properties have improved.

PMID- 20826558
TI  - Endobronchial foreign body removed by rigid bronchoscopy after 39 years.
AB  - A 64-year-old man accidentally fell into a wood chip tank and nearly suffocated
      in 1970. He frequently suffered from pneumonia after reaching the age of 40. In
      2009, he suffered from pneumonia again, and a chest computed tomography revealed
      a foreign body in the left main stem bronchus. Flexible bronchoscopy showed a
      wood chip lodged firmly in his bronchus. Removal using a flexible bronchoscope
      was attempted twice but failed. Rigid bronchoscopy was then performed under
      general anesthesia, and the chip was successfully extracted by cutting it in two
      using rigid scissors.

PMID- 20826559
TI  - Target of rapamycin signaling in leukemia and lymphoma.
AB  - Growth factors and many oncogenes activate the lipid kinase phosphoinositide 3
      kinase (PI3K), initiating a signaling cascade that includes the protein kinases
      AKT and target of rapamycin (TOR). The PI3K/AKT/TOR signaling pathway is a
      significant contributor to disease in various human cancers, including
      hematologic malignancies. Here we discuss different strategies to inhibit TOR for
      the treatment of leukemia, lymphoma, and myeloma. The TOR enzyme exists in two
      complexes in cells, TORC1 and TORC2. The majority of preclinical and clinical
      efforts to target TOR have involved using rapamycin and its analogs (rapalogs),
      which suppress TORC1 only partially and do not acutely inhibit TORC2. A new class
      of small molecules targeting the ATP-binding site of the TOR kinase, termed
      active-site TOR inhibitors (asTORi), achieves greater inhibition of both TOR
      complexes, resulting in broader suppression of the PI3K/AKT/TOR signaling
      network. Preclinical evidence suggests that asTORi have greater efficacy than
      rapalogs in Philadelphia chromosome-positive acute lymphoblastic leukemia and in
      T-cell lymphoma. These agents also show greater tolerability in animal models
      relative to rapalogs or inhibitors of PI3K. These findings encourage broader
      evaluation of asTORi efficacy in acute myeloid leukemia, B-cell lymphoma,
      myeloma, and other blood cancers.

PMID- 20826560
TI  - Contribution of fructose-6-phosphate to glucocorticoid activation in the
      endoplasmic reticulum: possible implication in the metabolic syndrome.
AB  - Both fructose consumption and increased intracellular glucocorticoid activation
      have been implicated in the pathogenesis of the metabolic syndrome.
      Glucocorticoid activation by 11beta-hydroxysteroid dehydrogenase type 1 (11beta
      HSD1) depends on hexose-6-phosphate dehydrogenase (H6PD), which physically
      interacts with 11beta-HSD1 at the luminal surface of the endoplasmic reticulum
      (ER) membrane and generates reduced nicotinamide adenine dinucleotide phosphate
      for the reduction of glucocorticoids. The reducing equivalents for the reaction
      are provided by glucose-6-phosphate (G6P) that is transported by G6P translocase
      into the ER. Here, we show that fructose-6-phosphate (F6P) can substitute for G6P
      and is sufficient to maintain reductase activity of 11beta-HSD1 in isolated
      microsomes. Our findings indicate that the mechanisms of F6P and G6P transport
      across the ER membrane are distinct and provide evidence that F6P is converted to
      G6P in the ER lumen, thus yielding substrate for H6PD-dependent reduced
      nicotinamide adenine dinucleotide phosphate generation. Using the purified
      enzyme, we show that F6P cannot be directly dehydrogenated by H6PD, and we also
      excluded H6PD as a phosphohexose isomerase. Therefore, we postulate the existence
      of an ER luminal hexose-phosphate isomerase different from the cytosolic enzyme.
      The results suggest that cytosolic F6P promotes prereceptor glucocorticoid
      activation in white adipose tissue, which might have a role in the
      pathophysiology of the metabolic syndrome.

PMID- 20826561
TI  - Diet-induced obesity causes ghrelin resistance in arcuate NPY/AgRP neurons.
AB  - Circulating ghrelin is decreased in obesity, and peripheral ghrelin does not
      induce food intake in obese mice. We investigated whether ghrelin resistance was
      a centrally mediated phenomenon involving dysregulated neuropeptide Y (NPY) and
      agouti-related peptide (AgRP) circuits. We show that diet-induced obesity (DIO)
      (12 wk) suppresses the neuroendocrine ghrelin system by decreasing acylated and
      total plasma ghrelin, decreasing ghrelin and Goat mRNA in the stomach, and
      decreasing expression of hypothalamic GHSR. Peripheral (ip) or central
      (intracerebroventricular) ghrelin injection was able to induce food intake and
      arcuate nucleus Fos immunoreactivity in chow-fed but not high-fat diet-fed mice.
      DIO decreased expression of Npy and Agrp mRNA, and central ghrelin was unable to
      promote expression of these genes. Ghrelin did not induce AgRP or NPY secretion
      in hypothalamic explants from DIO mice. Injection of NPY
      intracerebroventricularly increased food intake in both chow-fed and high-fat
      diet-fed mice, indicating that downstream NPY/AgRP neural targets are intact and
      that defective NPY/AgRP function is a primary cause of ghrelin resistance.
      Ghrelin resistance in DIO is not confined to the NPY/AgRP neurons, because
      ghrelin did not stimulate growth hormone secretion in DIO mice. Collectively, our
      data suggests that DIO causes ghrelin resistance by reducing NPY/AgRP
      responsiveness to plasma ghrelin and suppressing the neuroendocrine ghrelin axis
      to limit further food intake. Ghrelin has a number of functions in the brain
      aside from appetite control, including cognitive function, mood regulation, and
      protecting against neurodegenerative diseases. Thus, central ghrelin resistance
      may potentiate obesity-related cognitive decline, and restoring ghrelin
      sensitivity may provide therapeutic outcomes for maintaining healthy aging.

PMID- 20826562
TI  - Antifibrotic properties of relaxin: in vivo mechanism of action in experimental
      renal tubulointerstitial fibrosis.
AB  - This study examined the efficacy and in vivo mechanism of action of the
      antifibrotic hormone, relaxin, in a mouse model of unilateral ureteric
      obstruction (UUO). Kidney fibrosis was assessed in recombinant human gene-2
      relaxin-treated animals maintained for 3 and 9 d after UUO. Results were compared
      with untreated and unoperated animals (d 0). Total collagen, collagen subtypes
      (I, IV), TGF-beta2 production, mothers against decapentaplegic homolog 2 (Smad2)
      phosphorylation, myofibroblast differentiation, mitosis, and apoptosis were all
      progressively increased by UUO (all P<0.05 vs. d 0 group at d 3 and d 9), whereas
      TGF-beta1 production was increased and vascular endothelial growth factor
      expression (angiogenesis) decreased at d 9 (both P<0.05 vs. d 0). A progressive
      increase in matrix metalloproteinase (MMP)-2 after UUO suggested that it was
      reactive to the increased fibrogenesis. Conversely, MMP-9 was decreased at d 9,
      whereas its inhibitor tissue inhibitor of metalloproteinase-1 progressively
      decreased after UUO. Human gene-2 relaxin pretreatment of animals from 4 d prior
      to UUO ameliorated the increase in total collagen, collagen IV, Smad2
      phosphorylation, and myofibroblasts at both time points (all P<0.05 vs. untreated
      groups) and inhibited TGF-beta2 production and cell proliferation (both P<0.05
      vs. untreated groups) with a trend toward normalizing vascular endothelial growth
      factor expression at d 9, with no effect on TGF-beta1 production or apoptosis.
      The relaxin-mediated regulation of MMPs and tissue inhibitor of
      metalloproteinases in this model was not consistent with its antifibrotic
      properties. The beneficial effects of relaxin were lost when treatment was
      stopped. These findings establish that relaxin can inhibit both early and
      established phases of tubulointerstitial fibrosis, primarily by suppressing cell
      proliferation, myofibroblast differentiation, and collagen production. Not all of
      these effects paralleled changes to TGF-beta-Smad signaling.

PMID- 20826563
TI  - N-glycosylation increases the circulatory half-life of human growth hormone.
AB  - Therapeutic use of recombinant GH typically involves daily sc injections. We
      examined the possibilities for prolonging the in vivo circulation of GH by
      introducing N-glycans. Human GH variants with a single potential N-glycosylation
      site (N-X-S/T) introduced by site-directed mutagenesis were expressed in HEK293
      cells. In a scan of 15 different positions for N-glycosylation sites, four
      positions (amino acids 93, 98, 99, and 101) were efficiently utilized and did not
      influence GH in vitro activity. A GH variant (3N-GH) with all these sites was
      produced in CHOK1SV cells and contained up to three N-glycans. Two pools of 3N-GH
      were purified and separated according to their charge by anion-exchange
      chromatography. Anion-exchange HPLC revealed that the N-glycans in the two pools
      were very similar except for the extent of sialylation. Both 3N-GH pools
      circulated longer in rats than wild-type GH. The terminal half-life of 3N-GH
      after iv injection was 24-fold prolonged compared with wild-type GH for the pool
      with the most pronounced sialylation, 13-fold prolonged for the less sialylated
      pool, and similar to the wild-type for desialylated 3N-GH. The less sialylated 3N
      GH pool exhibited a profound pharmacodynamic effect in GH-deficient rats. Over a
      4-d period, a single injection of 3N-GH induced a stronger IGF-I response and a
      larger increase in body weight than daily injections with wild-type GH. Thus, N
      glycans can prolong the in vivo circulation and enhance the pharmacodynamic
      effect of GH. Sialic acids seem to play a pivotal role for the properties of
      glycosylated GH.

PMID- 20826564
TI  - Apolipoprotein A-I mimetic peptides prevent atherosclerosis development and
      reduce plaque inflammation in a murine model of diabetes.
AB  - OBJECTIVE: To determine the effect of the apolipoprotein A-I (ApoA-I) mimetic
      peptide, D-4F, on atherosclerosis development in a pre-existing diabetic
      condition. RESEARCH DESIGN AND METHODS: We induced hyperglycemia in 6-week-old
      apoE(-/-) female mice using streptozotocin. Half of the diabetic apoE(-/-) mice
      received D-4F in drinking water. Ten weeks later, plasma lipids, glucose, insulin
      levels, atherosclerotic lesions, and lesion macrophage content were measured.
      RESULTS: Diabetic apoE(-/-) mice developed ~300% more lesion area, marked
      dyslipidemia, increased glucose levels, and reduced plasma insulin levels when
      compared with nondiabetic apoE(-/-) mice. Atherosclerotic lesions were
      significantly reduced in the D-4F-treated diabetic apoE(-/-) mice in whole aorta
      (1.11 +/- 0.73 vs. 0.58 +/- 0.44, percentage of whole aorta, P < 0.01) and in
      aortic roots (36,038 +/- 18,467 MUm2/section vs. 17,998 +/- 12,491 MUm2/section,
      P < 0.01) when compared with diabetic apoE(-/-) mice that did not receive D-4F.
      Macrophage content in atherosclerotic lesions from D-4F-treated diabetic apoE(-/
      ) mice was significantly reduced when compared with nontreated animals (78.03 +/-
      26.1 vs. 29.6 +/- 15.2 P < 0.001, percentage of whole plaque). There were no
      differences in glucose, insulin, total cholesterol, HDL cholesterol, and
      triglyceride levels between the two groups. Arachidonic acid, PGE2, PGD2, 15
      HETE, 12-HETE, and 13-HODE concentrations were significantly increased in the
      liver tissue of diabetic apoE(-/-) mice compared with nondiabetic apoE(-/-) mice
      and significantly reduced by D-4F treatment. CONCLUSIONS: Our results suggest
      that oral D-4F can prevent atherosclerosis development in pre-existing diabetic
      mice and this is associated with a reduction in hepatic arachidonic acid and
      oxidized fatty acid levels.

PMID- 20826565
TI  - Pharmacological chaperones restore function to MC4R mutants responsible for
      severe early-onset obesity.
AB  - Heterozygous null mutations in the melanocortin-4 receptor (MC4R) cause early
      onset obesity in humans, indicating that metabolic homeostasis is sensitive to
      quantitative variation in MC4R function. Most of the obesity-causing MC4R
      mutations functionally characterized so far lead to intracellular retention of
      receptors by the cell's quality control system. Thus, recovering cell surface
      expression of mutant MC4Rs could have a beneficial therapeutic value. We tested a
      pharmacological chaperone approach to restore cell surface expression and
      function of 10 different mutant forms of human melanocortin-4 receptor found in
      obese patients. Five cell-permeant MC4R-selective ligands were tested and
      displayed pharmacological chaperone activities, restoring cell surface targeting
      and function of the receptors with distinct efficacy profiles for the different
      mutations. Such mutation-specific efficacies suggested a structure-activity
      relationship between compounds and mutant receptor conformations that may open a
      path toward personalized therapy. In addition, one of the five pharmacological
      chaperones restored function to most of the mutant receptors tested. Combined
      with its ability to reach the central nervous system and its selectivity for the
      MC4R, this pharmacological chaperone may represent a candidate for the
      development of a targeted therapy suitable for a large subset of patients with
      MC4R-deficient obesity.

PMID- 20826566
TI  - Dexamethasone enhances ATP-induced inflammatory responses in endothelial cells.
AB  - The purinergic nucleotide ATP is released from stressed cells and is implicated
      in vascular inflammation. Glucocorticoids are essential to stress responses and
      are used therapeutically, yet little information is available that describes the
      effects of glucocorticoids on ATP-induced inflammation. In a human microvascular
      endothelial cell line, extracellular ATP-induced interleukin (IL)-6 secretion in
      a dose- and time-dependent manner. When cells were pretreated with dexamethasone,
      a prototypic glucocorticoid, ATP-induced IL-6 production was enhanced in a time-
      and dose-dependent manner. Mifepristone, a glucocorticoid receptor antagonist,
      blocked these effects. ATP-induced IL-6 release was significantly inhibited by a
      phospholipase C inhibitor [1-[6-[((17beta)-3-methoxyestra-1,3,5[10]-trien-17
      yl)amino]hexyl]-1H-pyrrole-2,5-dione (U73122)] (63.2 +/- 3%, p < 0.001) and
      abolished by a p38 mitogen-activated protein kinase inhibitor [4-(4-fluorophenyl)
      2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole (SB 203580)] (88 +/- 1%, p
      < 0.001). Cells treated with dexamethasone induced mRNA expression of the
      purinergic P2Y(2) receptor (P2Y(2)R) 1.8- +/- 0.1-fold and, when stimulated with
      ATP, enhanced Ca(2+) release and augmented IL-6 mRNA expression. Silencing of the
      P2Y(2)R by its small interfering RNA decreased ATP-induced IL-6 production by 81
      +/- 1% (p < 0.001). Dexamethasone enhanced the transcription rate of P2Y(2)R mRNA
      and induced a dose-related increase in the activity of the P2Y(2)R promoter.
      Furthermore, dexamethasone-enhanced ATP induction of adhesion molecule
      transcription and augmented the release of IL-8. Dexamethasone leads to an
      unanticipated enhancement of endothelial inflammatory mediator production by
      extracellular ATP via a P2Y(2)R-dependent mechanism. These data define a novel
      positive feedback loop of glucocorticoids and ATP-induced endothelial
      inflammation.

PMID- 20826567
TI  - Prevention of bleomycin-induced pulmonary fibrosis by a novel antifibrotic
      peptide with relaxin-like activity.
AB  - Pulmonary fibrosis is a progressive and lethal lung disease characterized by
      accumulation of extracellular matrix and loss of pulmonary function. No cure
      exists for this pathologic condition, and current treatments often fail to slow
      its progression or relieve its symptoms. Relaxin was previously shown to induce a
      matrix-degrading phenotype in human lung fibroblasts in vitro and to inhibit
      pulmonary fibrosis in vivo. A novel peptide that targets the relaxin RXFP1/LGR7
      receptor was recently identified using our computational platform designed to
      predict novel G protein-coupled receptor peptide agonists. In this study, we
      examined the antifibrotic properties of this novel peptide, designated CGEN25009,
      in human cell-based assays and in a murine model of bleomycin-induced pulmonary
      fibrosis. Similar to relaxin, CGEN25009 was found to have an inhibitory effect on
      transforming growth factor-beta1-induced collagen deposition in human dermal
      fibroblasts and to enhance MMP-2 expression. The peptide's biological activity
      was also similar to relaxin in generating cellular stimulation of cAMP, cGMP, and
      NO in the THP-1 human cell line. In vivo, 2-week administration of CGEN25009 in a
      preventive or therapeutic mode (i.e., concurrently with or 7 days after bleomycin
      treatment, respectively) caused a significant reduction in lung inflammation and
      injury and ameliorated adverse airway remodeling and peribronchial fibrosis. The
      results of this study indicate that CGEN25009 displays antifibrotic and anti
      inflammatory properties and may offer a new therapeutic option for the treatment
      of pulmonary fibrosis.

PMID- 20826569
TI  - Vasopressin V2 receptors, ENaC, and sodium reabsorption: a risk factor for
      hypertension?
AB  - Excessive sodium reabsorption by the kidney has long been known to participate in
      the pathogenesis of some forms of hypertension. In the kidney, the final control
      of NaCl reabsorption takes place in the distal nephron through the amiloride
      sensitive epithelial sodium channel (ENaC). Liddle's syndrome, an inherited form
      of hypertension due to gain-of-function mutations in the genes coding for ENaC
      subunits, has demonstrated the key role of this channel in the sodium balance.
      Although aldosterone is classically thought to be the main hormone regulating
      ENaC activity, several studies in animal models and in humans highlight the
      important effect of vasopressin on ENaC regulation and sodium transport. This
      review summarizes the effect of vasopressin V2 receptor stimulation on ENaC
      activity and sodium excretion in vivo. Moreover, we report the experimental and
      clinical data demonstrating the role of renal ENaC in water conservation at the
      expense of a reduced ability to excrete sodium. Acute administration of the
      selective V2 receptor agonist dDAVP not only increases urine osmolality and
      reduces urine flow rate but also reduces sodium excretion in rats and humans.
      Chronic V2 receptor stimulation increases blood pressure in rats, and a
      significant correlation was found between blood pressure and urine concentration
      in healthy humans. This led us to discuss how excessive vasopressin-dependent
      ENaC stimulation could be a risk factor for sodium retention and resulting
      increase in blood pressure.

PMID- 20826568
TI  - A transmembrane amino acid in the GABAA receptor beta2 subunit critical for the
      actions of alcohols and anesthetics.
AB  - Alcohols and inhaled anesthetics enhance the function of GABA(A) receptors
      containing alpha, beta, and gamma subunits. Molecular analysis has focused on the
      role of the alpha subunits; however, there is evidence that the beta subunits may
      also be important. The goal of our study was to determine whether Asn265, which
      is homologous to the site implicated in the alpha subunit (Ser270), contributes
      to an alcohol and volatile anesthetic binding site in the GABA(A) receptor
      beta(2) subunit. We substituted cysteine for Asn265 and exposed the mutant to the
      sulfhydryl-specific reagent octyl methanethiosulfonate (OMTS). We used two
      electrode voltage-clamp electrophysiology in Xenopus laevis oocytes and found
      that, after OMTS application, GABA-induced currents were irreversibly potentiated
      in mutant alpha(1)beta(2)(N265C)gamma(2S) receptors [but not
      alpha(1)beta(2)(I264C)gamma(2S)], presumably because of the covalent linking of
      octanethiol to the thiol group in the substituted cysteine. It is noteworthy that
      this effect was blocked when OMTS was applied in the presence of octanol. We
      found that potentiation by butanol, octanol, or isoflurane in the N265C mutant
      was nearly abolished after the application of OMTS, suggesting that an alcohol
      and volatile anesthetic binding site at position 265 of the beta(2) subunit was
      irreversibly occupied by octanethiol and consequently prevented butanol or
      isoflurane from binding and producing their effects. OMTS did not affect
      modulation or direct activation by pentobarbital, but there was a partial
      reduction of allosteric modulation by flunitrazepam and alphaxalone in mutant
      alpha(1)beta(2)(N265C)gamma(2S) receptors after OMTS was applied. Our findings
      provide evidence that Asn265 may contribute to an alcohol and anesthetic binding
      site.

PMID- 20826570
TI  - Darbepoetin-alpha treatment enhances glomerular regenerative process in the Thy-1
      glomerulonephritis model.
AB  - Recent studies have demonstrated that erythropoietin (EPO) and its analogs induce
      cytoprotective effects on many nonerythroid cells. In this study, we examined
      whether darbepoetin-alpha might prevent glomerular lesions in the Thy-1.1 model
      of glomerulonephritis (Thy-1-GN). GN was induced in Wistar rats by a single
      injection of monoclonal anti-Thy-1.1 antibody. Rats were killed at 24 h, 72 h, 7
      days, 10 days, or 15 days after antibody injection. Kidneys were removed for
      histological analysis, and proteinuria was measured. Because at day 7 the maximal
      degree of renal damage and proteinuria was found, the effect of darbepoetin-alpha
      was tested at day 7 and two different protocols of administration were used;
      After anti-Thy-1.1 injection, rats received two doses of darbepoetin-alpha or
      vehicle at days 0 and 4 or at days 4 and 6. At day 7, proteinuria, plasma
      creatinine concentration, and renal morphology analysis were performed. Also,
      alpha-actin, desmin, caspase-3, and Ki67 protein expression were evaluated by
      immunohistochemistry. Our results showed that in both protocols of
      administration, darbepoetin-alpha treatment decreased proteinuria in Thy-1-GN
      rats and this effect correlated with the improvement in renal morphology.
      Glomerular lesions, alpha-actin, and caspase-3 protein expression, observed in
      most glomeruli of Thy-1-GN rats, were significantly reduced in darbepoetin-alpha
      treated rats, while cell proliferation was significantly enhanced. The results
      indicate that darbepoetin-alpha treatment promotes glomerular recovery.

PMID- 20826571
TI  - Sleep pattern in an experimental model of chronic kidney disease.
AB  - The prevalence of sleep disorders is significantly elevated in chronic kidney
      disease (CKD) patients. Numerous factors likely contribute to the high prevalence
      of sleep problems in uremic patients. The objective of this study was to evaluate
      the long-term sleep pattern changes in uremic rats during disease progression.
      Sleep recordings of the rats were monitored during light and dark periods that
      lasted 12 h each. These recordings were performed on days 7, 30, 60, and 90 after
      CKD induction. Cardiovascular, hormonal, and biochemical changes were evaluated
      at these same time points in control and uremic rats. CKD progression was
      reflected by the presence of hypertension and progressive increases in urea,
      creatinine, and cholesterol levels. We also observed hormonal fluctuations of
      corticosterone and ACTH, which indicated a potential alteration in the
      hypothalamic-pituitary-adrenal axis in diseased rats. In addition, rats with CKD
      demonstrated fragmented sleep with a greater number of arousals and decreased
      sleep efficiency in the light period during disease progression. In the dark
      period, there was an initial increase in sleep efficiency in CKD rats, but after
      90 days of CKD, these animals slept less compared with the control group.
      Collectively, these metabolic and cardiovascular changes were associated with the
      persistent alterations in sleep architecture observed in CKD rats.

PMID- 20826572
TI  - Renal hemodynamic effects elicited by acute cyclooxygenase-2 inhibition are not
      related to angiotensin II levels.

PMID- 20826573
TI  - Tubular cell-enriched subpopulation of primary renal cells improves survival and
      augments kidney function in rodent model of chronic kidney disease.
AB  - Established chronic kidney disease (CKD) may be identified by severely impaired
      renal filtration that ultimately leads to the need for dialysis or kidney
      transplant. Dialysis addresses only some of the sequelae of CKD, and a
      significant gap persists between patients needing transplant and available
      organs, providing impetus for development of new CKD treatment modalities. Some
      postulate that CKD develops from a progressive imbalance between tissue damage
      and the kidney's intrinsic repair and regeneration processes. In this study we
      evaluated the effect of kidney cells, delivered orthotopically by
      intraparenchymal injection to rodents 4-7 wk after CKD was established by two
      step 5/6 renal mass reduction (NX), on the regeneration of kidney function and
      architecture as assessed by physiological, tissue, and molecular markers. A proof
      of concept for the model, cell delivery, and systemic effect was demonstrated
      with a heterogeneous population of renal cells (UNFX) that contained cells from
      all major compartments of the kidney. Tubular cells are known contributors to
      kidney regeneration in situ following acute injury. Initially tested as a
      control, a tubular cell-enriched subpopulation of UNFX (B2) surprisingly
      outperformed UNFX. Two independent studies (3 and 6 mo in duration) with B2
      confirmed that B2 significantly extended survival and improved renal filtration
      (serum creatinine and blood urea nitrogen). The specificity of B2 effects was
      verified by direct comparison to cell-free vehicle controls and an equivalent
      dose of non-B2 cells. Quantitative histological evaluation of kidneys at 6 mo
      after treatment confirmed that B2 treatment reduced severity of kidney tissue
      pathology. Treatment-associated reduction of transforming growth factor (TGF)
      beta1, plasminogen activator inhibitor (PAI)-1, and fibronectin (FN) provided
      evidence that B2 cells attenuated canonical pathways of profibrotic extracellular
      matrix production.

PMID- 20826574
TI  - Connecting tubule glomerular feedback antagonizes tubuloglomerular feedback in
      vivo.
AB  - In vitro experiments showed that the connecting tubule (CNT) sends a signal that
      dilates the afferent arteriole (Af-Art) when Na(+) reabsorption in the CNT lumen
      increases. We call this process CNT glomerular feedback (CTGF) to differentiate
      it from tubuloglomerular feedback (TGF), which is a cross talk between the macula
      densa (MD) and the Af-Art. In TGF, the MD signals the Af-Art to constrict when
      NaCl transport by the MD is enhanced by increased luminal NaCl. CTGF is mediated
      by CNT Na(+) transport via epithelial Na(+) channels (ENaC). However, we do not
      know whether CTGF occurs in vivo or whether it opposes the increase in Af-Art
      resistance caused by TGF. We hypothesized that CTGF occurs in vivo and opposes
      TGF. To test our hypothesis, we conducted in vivo micropuncture of individual rat
      nephrons, measuring stop-flow pressure (P(SF)) as an index of glomerular
      filtration pressure. To test whether activation of CTGF opposes TGF, we used
      benzamil to block CNT Na(+) transport and thus CTGF. CTGF inhibition with the
      ENaC blocker benzamil (1 MUM) potentiated the decrease in P(SF) at 40 and 80
      nl/min. Next, we tested whether we could augment CTGF by inhibiting NaCl
      reabsorption in the distal convoluted tubule with hydrochlorothiazide (HCTZ, 1
      mM) to enhance NaCl delivery to the CNT. In the presence of HCTZ, benzamil
      potentiated the decrease in P(SF) at 20, 40, and 80 nl/min. We concluded that in
      vivo CTGF occurs and opposes the vasoconstrictor effect of TGF.

PMID- 20826575
TI  - The pathogenesis of cystinosis: mechanisms beyond cystine accumulation.
AB  - Renal proximal tubules are highly sensitive to ischemic and toxic insults and are
      affected in diverse genetic disorders, of which nephropathic cystinosis is the
      most common. The disease is caused by mutations in the CTNS gene, encoding the
      lysosomal cystine transporter cystinosin, and is characterized by accumulation of
      cystine in the lysosomes throughout the body. In the majority of the patients,
      this leads to generalized proximal tubular dysfunction (also called DeToni-Debre
      Fanconi syndrome) in the first year and progressive renal failure during the
      first decade. Extrarenal organs are affected by cystinosis as well, with clinical
      symptoms manifesting mostly after 10 yr of age. The cystine-depleting agent
      cysteamine significantly improves life expectancy of patients with cystinosis,
      but offers no cure, pointing to the complexity of the disease mechanism. In this
      review, current knowledge on the pathogenesis of cystinosis is described and
      placed in perspective of future research.

PMID- 20826576
TI  - Lack of {alpha}8-integrin aggravates podocyte injury in experimental diabetic
      nephropathy.
AB  - Development of diabetic nephropathy is accompanied by changes in integrin
      mediated cell-matrix interactions. The alpha8-integrin chain is specifically
      expressed in mesangial cells of the glomerulus. During experimental hypertension,
      alpha8-integrin plays a protective role in the glomerulus. We hypothesized that
      alpha8-integrin is involved in maintaining the integrity of the glomerulus in
      diabetic nephropathy. Experimental streptozotocin (STZ) diabetes led to an
      increased expression and glomerular deposition of alpha8-integrin. To test the
      functional role of alpha8-integrin, STZ diabetes was induced in mice with a
      homozygous (alpha8-/-) or heterozygous (alpha8+/-) deletion of the alpha8
      integrin gene and in wild-type litters (alpha8+/+). Blood glucose and mean
      arterial blood pressure were not different in alpha8-/- and alpha8+/+ mice after
      6 wk of diabetes. However, diabetic alpha8-/- mice developed significantly higher
      albuminuria and more glomerulosclerosis than diabetic alpha8+/+ mice. Moreover,
      in diabetic alpha8-/- mice, the number of glomerular cells staining positive for
      the podocyte markers WT-1 and vimentin were reduced more prominently than in
      diabetic alpha8+/+. The filtration barrier protein nephrin was downregulated in
      diabetic glomeruli with the strongest reduction observed in alpha8-/- mice. Taken
      together, alpha8-/- mice developed more severe glomerular lesions and podocyte
      damage after onset of STZ diabetes than alpha8+/+ mice, indicating that alpha8
      integrin is protective for the structure and function of the glomerulus and
      maintains podocyte integrity during the development of diabetic nephropathy.

PMID- 20826577
TI  - Baseline inhibin B and anti-Mullerian hormone measurements for diagnosis of
      hypogonadotropic hypogonadism (HH) in boys with delayed puberty.
AB  - CONTEXT: The diagnosis of isolated hypogonadotropic hypogonadism (IHH) in boys
      with delayed puberty is challenging, as may be the diagnosis of hypogonadotropic
      hypogonadism (HH) in boys with combined pituitary hormone deficiency (CPHD). Yet,
      the therapeutic choices for puberty induction depend on accurate diagnosis and
      may influence future fertility. OBJECTIVE: The aim was to assess the utility of
      baseline inhibin B (INHB) and anti-Mullerian hormone (AMH) measurements to
      discriminate HH from constitutional delay of puberty (CDP). Both hormones are
      produced by Sertoli cells upon FSH stimulation. Moreover, prepubertal AMH levels
      are high as a reflection of Sertoli cell integrity. PATIENTS: We studied 82 boys
      aged 14 to 18 yr with pubertal delay: 16 had IHH, 15 congenital HH within CPHD,
      and 51 CDP, as confirmed by follow-up. Subjects were genital stage 1 (testis
      volume<3 ml; 9 IHH, 7 CPHD, and 23 CDP) or early stage 2 (testis volume, 3-6 ml;
      7 IHH, 8 CPHD, and 28 CDP). RESULTS: Age and testis volume were similar in the
      three groups. Compared with CDP subjects, IHH and CPHD subjects had lower INHB,
      testosterone, FSH, and LH concentrations (P<0.05), whereas AMH concentration was
      lower only in IHH and CPHD subjects with genital stage 1, likely reflecting a
      smaller pool of Sertoli cells in profound HH. In IHH and CPHD boys with genital
      stage 1, sensitivity and specificity were 100% for INHB concentration of 35 pg/ml
      or less. In IHH and CPHD boys with genital stage 2, sensitivities were 86 and
      80%, whereas specificities were 92% and 88%, respectively, for an INHB
      concentration of 65 pg/ml or less. The performance of testosterone, AMH, FSH, and
      LH measurements was lower. No combination or ratio of hormones performed better
      than INHB alone. CONCLUSION: Discrimination of HH from CDP with baseline INHB
      measurement was excellent in subjects with genital stage 1 and fair in subjects
      with genital stage 2.

PMID- 20826579
TI  - Abrogation of TLR4 and CD14 expression and signaling in human adrenocortical
      tumors.
AB  - CONTEXT: Adrenocortical carcinoma (ACC) is a rare tumor with poor prognosis. The
      expression of innate immunity receptor Toll-like receptor 4 (TLR4) was recently
      reported in various human tumors, and TLR4 was shown to regulate tumor immune
      escape processes, proliferation, and resistance to chemotherapeutical agents.
      OBJECTIVE: The aim of this study was to investigate TLR4 expression, signaling,
      and function in the process of tumorigenesis in the human adrenal cortex.
      MEASUREMENTS AND MAIN RESULTS: Real-time PCR analysis of human ACC (n=8), adenoma
      (n=8), and ACC cell lines (SW13, NCI-H295R, and HAC15) revealed a significant
      down-regulation of TLR4, MD2 (myeloid differentiation protein-2), and cluster of
      differentiation 14 (CD14) mRNA compared with normal human adrenal cortex and
      adrenocortical cells in primary culture. Furthermore, immunohistochemistry
      revealed an abrogation of TLR4 and CD14 expression in ACC but not adenoma
      tissues. Western blot analysis of MAPK, AKT, activator protein-1, and nuclear
      factor-kappaB signaling revealed that the ACC cell lines are unresponsive to
      lipopolysaccharide action. Restoration of TLR4 signaling by stable transfection
      of TLR4-CD14 plasmid into NCI-H295R cells sensitized them to lipopolysaccharide
      incubation as shown by nuclear factor-kappaB activation and decreased cell
      viability and induced apoptosis in these cells. CONCLUSION: Our results
      demonstrate a significant reduction in the expression of TLR4 and CD14 and an
      inactivation of TLR4 signaling in ACCs. Furthermore, our data show that
      reintroduction of TLR4 expression in ACCs may provide a novel therapeutic
      strategy for adrenal cancer.

PMID- 20826578
TI  - Total testosterone assays in women with polycystic ovary syndrome: precision and
      correlation with hirsutism.
AB  - CONTEXT: There is no standardized assay of testosterone in women. Liquid
      chromatography mass spectrometry (LC/MS) has been proposed as the preferable
      assay by an Endocrine Society Position Statement. OBJECTIVE: The aim was to
      compare assay results from a direct RIA with two LC/MS. DESIGN AND SETTING: We
      conducted a blinded laboratory study including masked duplicate samples at three
      laboratories--two academic (University of Virginia, RIA; and Mayo Clinic, LC/MS)
      and one commercial (Quest, LC/MS). PARTICIPANTS AND INTERVENTIONS: Baseline
      testosterone levels from 596 women with PCOS who participated in a large,
      multicenter, randomized controlled infertility trial performed at academic health
      centers in the United States were run by varying assays, and results were
      compared. MAIN OUTCOME MEASURE: We measured assay precision and correlation and
      baseline Ferriman-Gallwey hirsutism scores. RESULTS: Median testosterone levels
      were highest with RIA. The correlations between the blinded samples that were run
      in duplicate were comparable. The correlation coefficient (CC) between LC/MS at
      Quest and Mayo was 0.83 [95% confidence interval (CI), 0.80-0.85], between RIA
      and LC/MS at Mayo was 0.79 (95% CI, 0.76-0.82), and between RIA and LC/MS at
      Quest was 0.67 (95% CI, 0.63-0.72). Interassay variation was highest at the lower
      levels of total testosterone (<=50 ng/dl). The CC for Quest LC/MS was
      significantly different from those derived from the other assays. We found
      similar correlations between total testosterone levels and hirsutism score with
      the RIA (CC=0.24), LC/MS at Mayo (CC=0.15), or Quest (CC=0.17). CONCLUSIONS: A
      testosterone RIA is comparable to LC/MS assays. There is significant variability
      between LC/MS assays and poor precision with all assays at low testosterone
      levels.

PMID- 20826580
TI  - Molecular classification of thyroid nodules using high-dimensionality genomic
      data.
AB  - OBJECTIVE: We set out to develop a molecular test that distinguishes benign and
      malignant thyroid nodules using fine-needle aspirates (FNA). DESIGN: We used mRNA
      expression analysis to measure more than 247,186 transcripts in 315 thyroid
      nodules, comprising multiple subtypes. The data set consisted of 178
      retrospective surgical tissues and 137 prospectively collected FNA samples. Two
      classifiers were trained separately on surgical tissues and FNAs. The performance
      was evaluated using an independent set of 48 prospective FNA samples, which
      included 50% with indeterminate cytopathology. RESULTS: Performance of the tissue
      trained classifier was markedly lower in FNAs than in tissue. Exploratory
      analysis pointed to differences in cellular heterogeneity between tissues and
      FNAs as the likely cause. The classifier trained on FNA samples resulted in
      increased performance, estimated using both 30-fold cross-validation and an
      independent test set. On the test set, negative predictive value and specificity
      were estimated to be 96 and 84%, respectively, suggesting clinical utility in the
      management of patients considering surgery. Using in silico and in vitro mixing
      experiments, we demonstrated that even in the presence of 80% dilution with
      benign background, the classifier can correctly recognize malignancy in the
      majority of FNA samples. CONCLUSIONS: The FNA-trained classifier was able to
      classify an independent set of FNAs in which substantial RNA degradation had
      occurred and in the presence of blood. High tolerance to dilution makes the
      classifier useful in routine clinical settings where sampling error may be a
      concern. An ongoing multicenter clinical trial will allow us to validate
      molecular test performance on a larger independent test set of prospectively
      collected thyroid FNAs.

PMID- 20826581
TI  - Functional consequences of dual oxidase-thyroperoxidase interaction at the plasma
      membrane.
AB  - CONTEXT: Thyroperoxidase (TPO) and dual oxidase (DUOX) are present at the apical
      membrane of thyrocytes, where TPO catalyzes thyroid hormone biosynthesis in the
      presence of H2O2 produced by DUOX. Both enzymes are colocalized and associated,
      but the consequences of this interaction remain obscure. OBJECTIVE: The objective
      of this study was to evaluate the functional consequences of TPO-DUOX interaction
      at the plasma membrane. DESIGN: The functional consequences of DUOX-TPO
      interaction were studied by measuring extracellular H2O2 concentration and TPO
      activity in a heterologous system. For this purpose, HEK293 cells were
      transiently transfected with a combination of human TPO with human DUOX1 or DUOX2
      in the presence of their respective maturation factors, DUOXA1 or DUOXA2. The
      effect of human DUOX2 mutants in which cysteine residues in the N-terminal domain
      were replaced by glycines was also analyzed. RESULTS: We observed that production
      of H2O2 decreases both TPO and DUOX activities. We show that TPO presents a
      catalase-like effect that protects DUOX from inhibition by H2O2. This catalase
      like effect depends on the association between both enzymes, which probably
      occurs through the DUOX peroxidase-like domain because this effect was not
      observed with human DUOX2 mutants. CONCLUSION: The DUOX-TPO association at the
      plasma membrane is relevant for normal enzyme properties. Normally, TPO consumes
      H2O2 produced by DUOX, decreasing the availability of this substance at the
      apical membrane of thyrocytes and, in turn, probably decreasing the oxidative
      damage of macromolecules.

PMID- 20826582
TI  - Reduced energy expenditure and impaired feeding-related signals but not high
      energy intake reinforces hypothalamic obesity in adults with childhood onset
      craniopharyngioma.
AB  - CONTEXT: Obesity is a frequent manifestation of hypothalamic damage from a
      craniopharyngioma (CP). It is not yet clarified whether the obesity is due to
      alterations in energy expenditure, i.e. basal metabolic rate (BMR) and physical
      activity, or to increased energy intake (EI). OBJECTIVE: The aim was to
      investigate whether energy expenditure and EI differed between childhood onset CP
      patients and matched population controls and whether these measures were related
      to hypothalamic damage, as tumor growth into the third ventricle (TGTV). DESIGN
      AND METHODS: Forty-two CP patients (20 women) aged 28 yr (range, 17-57 yr)
      operated between 1958 and 2000 in the South Medical Region of Sweden (population,
      2.5 million) were studied. Body composition, satiety hormones, BMR (indirect
      calorimetry), physical activity, EI, and attitudes toward eating were assessed.
      Comparisons were made with matched controls and between patients with (n=25) and
      without (n=17) TGTV. RESULTS: After adjustment, patients had lower BMR compared
      to controls (-90 kcal/24 h; P=0.02) and also had lower EI (1778 vs. 2094 kcal/24
      h; P=0.008), and the EI/BMR ratio was significantly lower in TGTV patients.
      Similar dietary macronutrient composition was found, and only significantly
      higher scales in restricting food intake were recorded in patients. Ghrelin
      levels were significantly lower in patients, whereas serum insulin and leptin
      levels were higher (P<0.001), and both ghrelin and insulin correlated
      significantly to tumor growth. Lower levels of physical activity (P<0.01) were
      recorded in patients. CONCLUSIONS: The major mechanisms that reinforced obesity
      were hypothalamic damage causing disrupted or impaired sensitivity to feeding
      related signals for leptin, insulin, and ghrelin, and reductions in both BMR and
      physical activity.

PMID- 20826583
TI  - The impact of genetic variation in the G6PC2 gene on insulin secretion depends on
      glycemia.
AB  - CONTEXT: Single-nucleotide polymorphisms (SNPs) within the G6PC2 locus are
      associated with fasting glucose and insulin secretion. These SNPs are not
      associated with type 2 diabetes risk. OBJECTIVE: Our objective was to investigate
      whether the impact of the SNP on variables of glucose-stimulated insulin
      secretion is influenced by glucose tolerance status. DESIGN, SETTING,
      PARTICIPANTS, AND INTERVENTION: In this cross-sectional study, we genotyped 1505
      healthy Caucasian subjects [normal glucose tolerance (NGT), 1098; impaired
      glucose tolerance (IGT)/impaired fasting glucose (IFG), 407] for SNP rs560887
      within the G6PC2 locus. A subgroup of 326 subjects underwent an iv glucose
      tolerance test, and 512 participants took part in a hyperinsulinemic-euglycemic
      clamp. For replication, SNP rs560887 was genotyped in 457 subjects (NGT, 265;
      IGT, 192) from four independent German and Dutch studies who underwent a
      hyperglycemic clamp. MAIN OUTCOME MEASURE: Insulin secretion was evaluated.
      RESULTS: Carriers of the major G-allele exhibited increased fasting glycemia
      (P<0.0001). Insulin sensitivity and secretion were not associated with the SNP
      (P>=0.06). Glucose tolerance status and genotype interacted on insulin secretion
      (P=0.036), such that in NGT subjects, the minor A-allele of rs560887 was
      associated with decreased insulinogenic index (P=0.044), which was not the case
      in subjects with IFG/IGT (P=1.0). During the iv glucose tolerance test, an
      association of A-allele carriers with decreased first-phase insulin secretion was
      also observed only in NGT subjects (P=0.0053). Likewise, in the hyperglycemic
      clamp group, the A-allele was associated with decreased first-phase insulin
      secretion only in the NGT group (P=0.022) but not in the IGT group. CONCLUSIONS:
      The effects of hyperglycemia on insulin secretion override the more subtle
      effects of genetic variation in the G6PC2 locus on insulin secretion.

PMID- 20826584
TI  - Specifically PNPLA3-mediated accumulation of liver fat in obese patients with
      type 2 diabetes.
AB  - CONTEXT: Recently, it has been shown in the general population that an allele in
      the adiponutrin (PNPLA3) gene was strongly associated with increased liver fat
      content (LFC), independently of visceral adiposity and insulin resistance.
      OBJECTIVE: In this study, we set out to determine whether LFC, evaluated using
      (1)H-MR spectroscopy, was associated with PNPLA3 rs738409 polymorphism in people
      with type 2 diabetes. We also evaluated the influence of this polymorphism on the
      relationship between LFC and either visceral adiposity or carotid intima media
      thickness (CIMT). DESIGN, SETTINGS, AND PARTICIPANTS: A total of 218 type 2
      diabetic patients were included in this study. MAIN OUTCOME MEASURES: LFC, area
      of visceral fat, and CIMT were measured. RESULTS: A total of 139 (63.7%) patients
      had steatosis. The rs738409 minor G allele was associated with LFC. The number of
      patients with steatosis was significantly higher among minor G allele carriers in
      comparison to C allele homozygote carriers (70.3 vs. 57.2%; P=0.04) In the
      subgroup of C allele homozygote carriers, LFC correlated with body mass index
      (r=0.27; P=0.003) and visceral fat area (r=0.30; P=0.002), but not with CIMT. In
      the subgroup of minor G allele carriers, LFC correlated inversely with CIMT (r=
      0.23; P=0.03), but not with body mass index or with visceral fat area. In
      multivariate logistic regression, the relationship between the highest quartile
      of CIMT and steatosis was different according to adiponutrin polymorphism.
      CONCLUSIONS: This study confirms that in people with type 2 diabetes, LFC is
      related to rs738409 polymorphism. The lack of a relationship with visceral
      obesity and the inverse correlation with CIMT suggest that fatty liver associated
      with the minor G allele of the PNPLA3 rs738409 polymorphism may not be linked to
      metabolic disorders.

PMID- 20826585
TI  - Statins inhibit growth of human theca-interstitial cells in PCOS and non-PCOS
      tissues independently of cholesterol availability.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) is associated with ovarian enlargement,
      prominent theca-interstitial hyperplasia, and excessive androgen production.
      Recent clinical trials have demonstrated that statins, 3-hydroxy-3-methyl
      glutaryl-CoA reductase inhibitors, decrease androgen levels in women with PCOS.
      OBJECTIVE: The present study evaluated the effect of statins on proliferation of
      human ovarian theca-interstitial cells. DESIGN AND SETTINGS: In vitro experiments
      were performed in the university research laboratory. PATIENTS: Human theca
      interstitial cells were isolated from ovaries of PCOS (n=4) and non-PCOS (n=4)
      patients. MAIN OUTCOME MEASURES: The cells were incubated for 48 h without
      additives (control) or with simvastatin (3-30 MUm), mevastatin (3-30 MUm), and/or
      the cell- and mitochondrion-permeable form of cholesterol (22-hydroxycholesterol;
      10 MUm). To determine whether the effects of statins could be affected by
      leukocytes, the experiment was carried out on cells not purified of leukocytes
      and cells purified using anti-CD-45 immunomagnetic beads. The effect of statins
      on proliferation was evaluated by determination of DNA synthesis using
      radiolabeled thymidine-incorporation assay and by quantification of viable cells
      using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenil)
      2H-tetrazolium assay. RESULTS: Statins induced an inhibition of DNA synthesis in
      both the absence and the presence of 22-hydroxycholesterol; furthermore, 22
      hydroxycholesterol alone also inhibited DNA synthesis. These effects of statins
      and 22-hydroxycholesterol were confirmed by 3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenil)-2H-tetrazolium assay. Comparable
      inhibition of proliferation was observed in cells obtained from women with and
      without PCOS and in cell preparations treated and not treated with anti-CD-45
      immunomagnetic beads. CONCLUSIONS: Statins inhibit proliferation of human theca
      interstitial cells irrespective of the availability of cholesterol and
      independently of leukocytes both in normal and PCOS ovaries.

PMID- 20826586
TI  - Cerebrospinal fluid corticosteroid levels and cortisol metabolism in patients
      with idiopathic intracranial hypertension: a link between 11beta-HSD1 and
      intracranial pressure regulation?
AB  - CONTEXT: The etiology of idiopathic intracranial hypertension (IIH) is unknown.
      We hypothesized that obesity and elevated intracranial pressure may be linked
      through increased 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1)
      activity. OBJECTIVE: The aim was to characterize 11beta-HSD1 in human
      cerebrospinal fluid (CSF) secretory [choroid plexus (CP)] and drainage [arachnoid
      granulation tissue (AGT)] structures, and to evaluate 11beta-HSD1 activity after
      therapeutic weight loss in IIH. DESIGN AND SETTING: We conducted in vitro
      analysis of CP and AGT and a prospective in vivo cohort study set in two tertiary
      care centers. PATIENTS OR OTHER PARTICIPANTS: Twenty-five obese adult female
      patients with active IIH were studied, and 22 completed the study. INTERVENTION:
      Fasted serum, CSF, and 24-h urine samples were collected at baseline, after 3
      month observation, and after a 3-month diet. MAIN OUTCOME MEASURES: Changes in
      urine, serum, and CSF glucocorticoids (measured by gas chromatography/mass
      spectrometry and liquid chromatography/tandem mass spectrometry) after weight
      loss were measured. RESULTS: 11beta-HSD1 and key elements of the glucocorticoid
      signaling pathway were expressed in CP and AGT. After weight loss (14.2+/-7.8 kg;
      P<0.001), global 11beta-HSD1 activity decreased (P=0.001) and correlated with
      reduction in intracranial pressure (r=0.504; P=0.028). CSF and serum
      glucocorticoids remained stable, although the change in CSF cortisone levels
      correlated with weight loss (r=-0.512; P=0.018). CONCLUSIONS: Therapeutic weight
      loss in IIH is associated with a reduction in global 11beta-HSD1 activity.
      Elevated 11beta-HSD1 may represent a pathogenic mechanism in IIH, potentially via
      manipulation of CSF dynamics at the CP and AGT. Although further clarification of
      the functional role of 11beta-HSD1 in IIH is needed, our results suggest that
      11beta-HSD1 inhibition may have therapeutic potential in IIH.

PMID- 20826587
TI  - MUC1 as a discriminator between endometrium from fertile and infertile patients
      with PCOS and endometriosis.
AB  - CONTEXT: Endometrium of fertile women expresses progesterone-regulated Mucin 1
      (MUC1) that carries selectin ligands recognized by the human blastocyst. Altered
      MUC1 expression at the time of implantation may contribute to endometrial
      infertility. OBJECTIVE: The aim was to assess the expression of MUC1 in the
      endometrium from polycystic ovary syndrome (PCOS), endometriosis, and fertile
      women in comparison with other hormone-regulated proteins [hydroxysteroid
      dehydrogenase (HSD) 1, HSD2, estrogen receptor (ER) and progesterone receptor
      (PR)]. DESIGN AND PATIENTS: Endometrial samples were obtained from 33 fertile
      patients, 26 ovulatory PCOS patients, 15 anovulatory PCOS patients, and 25
      endometriosis patients. MAIN OUTCOME MEASURE: Immunohistochemistry assessed the
      expression of MUC1 subunits ER, PR, HSD1, and HSD2 in endometrial epithelium.
      Endometrial MUC1 expression was quantified by immunoblots and RT-PCR. HSD1 and
      HSD2 expression was assayed by RT-PCR. RESULTS: MUC1ND expression was
      significantly higher in ovulatory PCOS than in fertile and anovulatory PCOS
      patients, even after progesterone stimulation. MUC1ND and -CD expression was
      lower in anovulatory PCOS than in fertile patients. Only MUC1CD expression was
      lower in endometriosis patients. Endometrial ER expression was significantly
      higher in PCOS and endometriosis patients, whereas PR expression was
      significantly higher in PCOS than in fertile patients. The expression of HSD1 was
      significantly higher in anovulatory PCOS than in fertile patients. Expression of
      HSD2 was significantly higher in PCOS patients and lower in endometriosis
      patients. CONCLUSION: Expression of MUC1 subunits in the infertile endometrium is
      significantly different from fertile and appears to be a component of altered
      gene expression that potentially contributes to endometrial insufficiency.

PMID- 20826588
TI  - Genetically elevated apolipoprotein A-I, high-density lipoprotein cholesterol
      levels, and risk of ischemic heart disease.
AB  - CONTEXT: Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol
      and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely
      related to risk of ischemic heart disease (IHD). OBJECTIVE: We tested whether
      common genetic variation in the apolipoprotein A1 gene (APOA1) contributes to
      apoA-I and HDL cholesterol levels and risk of IHD in the general population.
      DESIGN: We resequenced the regulatory and coding regions of APOA1 in 190
      individuals from the Copenhagen City Heart Study with the lowest 1% (n=95) and
      highest 1% (n=95) apoA-I levels. Two single-nucleotide polymorphisms (SNPs) were
      subsequently genotyped in the Copenhagen City Heart Study (n=10,273) and in 2361
      cases with IHD (the Copenhagen Ischemic Heart Disease Study). RESULTS: In total,
      13 genetic variants were identified. Three SNPs, g.-560A->C, g.-151C->T, and
      *181A->G, determined a haplotype that differed between high and low apoA-I groups
      (6 vs. 1%, P=0.002). Genotype combinations of two SNPs, the g.-560A->C (tagging
      the g.-560A->C/g.-151C->T/*181A->G haplotype) and g.-310G->A (situated near a
      potential functional promoter site), were associated with increases in apoA-I and
      HDL cholesterol levels of up to 6.6 and 8.5%, respectively, resulting in
      theoretically predicted reductions in risk of 9 and 8% for IHD and 14 and 12% for
      myocardial infarction (MI). Despite this, these same genotype combinations were
      not associated with decreased risk of IHD or MI. CONCLUSION: Common genetic
      variation in APOA1 associated with increased apoA-I and HDL cholesterol levels
      did not associate with decreased risk of IHD or MI.

PMID- 20826589
TI  - Fatherhood in tall men treated with high-dose sex steroids during adolescence.
AB  - BACKGROUND/OBJECTIVE: Sex steroid treatment to reduce final height of tall boys
      has been available since the 1950s. In women, it has been shown to interfere with
      fertility. In men, no such data are available. We therefore evaluated fertility
      and gonadal function in tall men who did or did not receive high-dose androgen
      treatment in adolescence. METHODS: We conducted a retrospective cohort study of
      116 tall men, of whom 60 had been treated. Reproductive and gonadal function was
      assessed by standardized interview, semen analysis, endocrine parameters,
      ultrasound imaging, and fatherhood. Mean age at treatment commencement was 14.2
      yr, and mean follow-up was 21.2 yr. RESULTS: Sixty-six men (36 treated and 30
      untreated) had attempted to achieve fatherhood. The probability of conceiving
      their first pregnancy within 1 yr was similar in treated and untreated men (26
      vs. 24; Breslow P=0.8). Eleven treated and 13 untreated men presented with a left
      sided varicocele (P=0.5). Testicular volume, sperm quality, and serum LH, FSH,
      and inhibin B levels were comparable between treated and untreated men. However,
      treated men had significantly reduced serum T levels, adjusted for known
      confounders [mean (sd) 13.3 (1.8) vs. 15.2 (1.9) nmol/liter; P=0.005). In
      addition, testicular volume and serum inhibin B and FSH levels in treated men
      were significantly correlated with age at treatment commencement. CONCLUSION: At
      a mean follow-up of 21 yr after high-dose androgen treatment, we conclude that
      fatherhood and semen quality in tall treated men are not affected. Serum
      testosterone levels, however, are reduced in androgen-treated men. Future
      research is required to determine whether declining testosterone levels may
      become clinically relevant for these men as they age.

PMID- 20826590
TI  - The challenge of patients with severe psychiatric illness who do not access care 
      a way forward.
AB  - Psychiatric illnesses are a significant cause of morbidity all over the world. In
      India many people with mental disorders are unable to access psychiatric care for
      a variety of reasons. This article describes the successful management of a
      person with schizophrenia in the community through a primary care team in liaison
      with psychiatrist services.

PMID- 20826591
TI  - Injection-induced sciatic nerve injury in Ugandan children.
AB  - In developing countries, sciatic nerve injury following gluteal intramuscular
      injection is a persistent problem. A study over 6 months involving 133 children
      seen in Mulago hospital with acute flaccid paralysis revealed 124 (93%) children
      with injection-induced sciatic nerve injury. The identity of the drug in 79 cases
      (59.4%) was quinine. It is recommended that the gluteal region should not be used
      as an intramuscular injection site in children.

PMID- 20826592
TI  - Remote Ischemic Conditioning in Patients With Myocardial Infarction Treated With
      Primary Angioplasty: Impact on Left Ventricular Function Assessed by
      Comprehensive Echocardiography and Gated Single-Photon Emission CT.
AB  - BACKGROUND: we have found that remote ischemic conditioning (rIC), adjunctive to
      primary angioplasty, increases myocardial salvage in patients with ST-segment
      elevation myocardial infarction (STEMI) and extensive myocardial area at risk
      (AAR). The present substudy aimed to evaluate the short-term effects of rIC on
      left ventricular (LV) function. METHODS AND RESULTS: patients with a first STEMI
      were randomized to rIC (4 cycles of 5 minutes upper-limb ischemia) during
      transfer to primary percutaneous coronary intervention (pPCI) (n=123) versus pPCI
      alone (n=119). Ejection fraction (EF), LV volumes, (2D and 3D echocardiography
      and myocardial perfusion imaging), and speckle-tracking global longitudinal
      strain were compared between treatment groups. There was no significant
      difference in LV function at day 1 (EF-2D, 0.51+/-0.10 versus 0.49+/-0.10;
      P=0.22) and after 30 days (EF-2D, 0.54+/-0.08 versus 0.53+/-0.10) between the rIC
      and the pPCI-alone groups. In patients with extensive AAR >=35% of LV (n=53), EF
      after 30 days was higher after rIC than after pPCI alone (EF-2D, 0.51+/-0.07
      versus 0.46+/-0.09; P=0.05). In patients with anterior infarction (n=97), rIC
      preserved LV function on day 1 (EF-2D, 0.51+/-0.11 versus 0.46+/-0.11; P=0.03)
      and persistently after 30 days (EF-2D, 0.55+/-0.08 versus 0.50+/-0.11; P=0.04; EF
      myocardial perfusion imaging, 0.55+/-0.10 versus 0.49+/-0.12; P=0.02). These
      patients had similar AAR, whereas rIC reduced infarct size from 16% to 7% of LV
      (P=0.01). CONCLUSIONS: although no significant overall effect was observed, rIC
      seemed to result in modest improvement in LV function in high-risk patients prone
      to develop large myocardial infarcts. These results need to be confirmed in
      larger trials.

PMID- 20826593
TI  - Dobutamine-induced improvement in inferior myocardial contractile function
      predicts reduction in functional mitral regurgitation: a study using tissue
      Doppler strain rate imaging.
AB  - BACKGROUND: left ventricular (LV) remodeling can increase tethering force to
      mitral valve and functional mitral regurgitation (FMR). Because the relationship
      between FMR and regional myocardial function has not been quantitatively
      evaluated, we conducted a quantitative investigation of this association. METHODS
      AND RESULTS: the effective regurgitant orifice (ERO) of FMR in 51 patients with
      depressed LV ejection fraction (32+/-9%) secondary to ischemic or nonischemic
      cardiomyopathy was compared with mitral deformation (valve and annulus), global
      LV remodeling (volume indices, function, and sphericity), and regional myocardial
      contractile function, as assessed by longitudinal peak systolic strain rate (Ssr)
      in LV anterior, anteroseptal, inferoseptal, inferior, inferolateral, and
      anterolateral segments at rest. Low-dose dobutamine (10 MUg/kg per minute)
      induced changes in ERO were compared with changes in the variables. Multivariable
      analysis identified the predictors of ERO at rest as mitral valvular tenting
      (beta=0.062; P<0.001), Ssr in the inferior segment (inferior Ssr) (beta=-0.178;
      P<0.001), and LV sphericity (beta=0.414; P=0.001) and the predictors of valvular
      tenting at rest as inferior Ssr (beta=-1.680; P<0.001), LV end-systolic volume
      index (beta=0.022; P=0.001), and LV sphericity (beta=3.886; P=0.012).
      Furthermore, dobutamine-induced reduction in ERO was predicted by reduction in
      valvular tenting (beta=0.087; P<0.001) and increase in inferior Ssr (beta=-0.082;
      P<0.001), and dobutamine-induced reduction in valvular tenting was predicted by
      increase in inferior Ssr (beta=-0.860; P<0.001). CONCLUSIONS: inferior regional
      myocardial dysfunction was quantitatively associated with mitral valvular tenting
      and FMR. Moreover, improvement with dobutamine of inferior myocardial contractile
      function attenuated valvular tenting and FMR. Inferior myocardial contractile
      function can affect the configuration of the mitral apparatus and predict FMR
      severity.

PMID- 20826594
TI  - Preload dependency of left ventricular torsion: the impact of normal saline
      infusion.
AB  - BACKGROUND: left ventricular (LV) rotation results from contraction of obliquely
      oriented myocardial fibers. The net difference between systolic apical
      counterclockwise rotation and basal clockwise rotation is left ventricular
      torsion (LVT). Although LVT is altered in various cardiac diseases, determinants
      of LVT are incompletely understood. METHODS AND RESULTS: LV end-diastolic volume,
      LV apical and basal rotation, peak systolic LVT, and peak early diastolic
      untwisting rate were measured by speckle-tracking echocardiography in healthy
      subjects (n=8) before and after infusion of a weight-based normal saline bolus
      (2.1+/-0.3 L). Saline infusion led to a significant increase in end-diastolic LV
      internal diameter (45.9+/-3.7 versus 47.6+/-4.2 mm; P=0.002) and LV end-diastolic
      volume (90.0+/-21.6 versus 98.3+/-19.6 mL; P=0.01). Stroke volume (51.3+/-10.9
      versus 63.0+/-15.5 mL; P=0.003) and cardiac output (3.4+/-0.8 versus 4.4+/-1.5
      L/min; P=0.007) increased, whereas there was no change in heart rate and blood
      pressure. There was a significant increase in the magnitude of peak systolic
      apical rotation (7.5+/-2.4 degrees  versus 10.5+/-2.8 degrees ; P<0.001) but no
      change in basal rotation (-4.1+/-2.3 degrees  versus -4.8+/-3.1 degrees ;
      P=0.44). Accordingly, peak systolic LVT increased by 33% after saline infusion
      (11.2+/-1.3 degrees  versus 14.9+/-1.7 degrees ; P<0.001). This saline-induced
      increase in LVT was associated with a marked increase in peak early diastolic
      untwisting rate (72.3+/-21.4 versus 136.8+/-30.0 degrees/s; P<0.001).
      CONCLUSIONS: peak systolic LVT and peak early diastolic untwisting rate are
      preload-dependent. Changes in LV preload should be considered when interpreting
      results of future LVT studies.

PMID- 20826596
TI  - Heparin confusion.

PMID- 20826595
TI  - Relief of mitral leaflet tethering following chronic myocardial infarction by
      chordal cutting diminishes left ventricular remodeling.
AB  - BACKGROUND: one of the key targets in treating mitral regurgitation (MR) is
      reducing the otherwise progressive left ventricular (LV) remodeling that
      exacerbates MR and conveys adverse prognosis. We have previously demonstrated
      that severing 2 second-order chordae to the anterior mitral leaflet relieves
      tethering and ischemic MR acutely. The purpose of this study was to test whether
      this technique reduces the progression of LV remodeling in the chronic ischemic
      MR setting. METHODS AND RESULTS: a posterolateral MI was created in 18 sheep by
      obtuse marginal branch ligation. After chronic remodeling and MR development at 3
      months, 6 sheep were randomized to sham surgery (control group) and 12 to second
      order chordal cutting (6 each to anterior leaflet [AntL] and bileaflet [BiL]
      chordal cutting, techniques that are in clinical application). At baseline,
      chronic infarction (3 months), and follow-up at a mean of 6.6 months post
      myocardial infarction (MI) (euthanasia), we measured LV end-diastolic (EDV) and
      end-systolic volume (ESV), ejection fraction, wall motion score index, and
      posterior leaflet (PL) restriction angle relative to the annulus by 2D and 3D
      echocardiography. All measurements were comparable among groups at baseline and
      chronic MI. At euthanasia, AntL and BiL chordal cutting limited the progressive
      remodeling seen in controls. LVESV increased relative to chronic MI by 109+/-8.7%
      in controls versus 30.5+/-6.1% with chordal cutting (P<0.01) (LVESV in controls,
      82.5+/-2.6 mL; in AntL, 60.6+/-5.1 mL; in BiL, 61.8+/-4.1 mL). LVEDV increased by
      63+/-2.0% in controls versus 26+/-5.5% and 22+/-3.4% with chordal cutting
      (P<0.01). LV ejection fraction and wall motion score index were not significantly
      different at follow-up among the chordal cutting and control groups. MR
      progressively increased to moderate in controls but decreased to trace-mild with
      AntL and BiL chordal cutting (MR vena contracta in controls, 5.9+/-1.1 mm; in
      AntL, 2.6+/-0.1 mm; in BiL, 1.7+/-0.1 mm; P<0.01). BiL chordal cutting provided
      greater PL mobility (decreased PL restriction angle to 54.2+/-5.0 degrees  versus
      83+/-3.2 degrees  with AntL chordal cutting; P<0.01). CONCLUSIONS: reduced
      leaflet tethering by chordal cutting in the chronic post-MI setting substantially
      decreases the progression of LV remodeling with sustained reduction of MR over a
      chronic follow-up. These benefits have the potential to improve clinical
      outcomes.

PMID- 20826597
TI  - Self-stress vs manual stress in talar tilt radiography.
AB  - BACKGROUND: Radiographic study following inversion ankle sprain commonly is used
      to determine the presence of anatomic laxity across the talocrural joint.
      PURPOSE: To compare the degree of talar tilt derived from a radiographic ankle
      stress exam under 2 conditions: self-stress vs manual stress applied by the
      clinician. METHODS: Twenty-four subjects seeking medical care following ankle
      sprain underwent talar tilt stress exams of both ankles. The involved ankle was
      imaged with self-stress by use of a strap and with the clinician providing manual
      stress during the imaging exam. Mean talar tilt for the self-stress method was
      2.2 degrees, compared with 5.9 degrees for the manual stress method (P < .001).
      RESULTS: Significantly greater and clinically meaningful differences in talar
      tilt angle were found when manual stress was provided by the clinician. To avoid
      false negative findings of anatomic laxity in stress talar tilt studies at the
      ankle, a standardized procedure in which the clinician provides manual stress may
      be necessary.

PMID- 20826598
TI  - Managing a mammography center: a model to thrive.
AB  - BACKGROUND: With the ever-increasing burdens of adhering to the Mammography
      Quality Standards Act (MQSA), it is important for mammography centers to use
      technology to work smarter and faster and capture as much revenue as possible. At
      the same time, patient satisfaction and employee satisfaction have a synergistic
      effect on the quality of patient care and the financial status of the clinic.
      METHOD: This comprehensive literature review examines the effects of MQSA,
      technology and patient and employee satisfaction on the operations of a quality
      breast imaging center. RESULTS: A best practice model is offered that combines
      the best of these elements based on current literature.

PMID- 20826599
TI  - Tuberculosis: a review and update.
AB  - More than 2 billion people worldwide are infected with Mycobacterium
      tuberculosis, the bacterium that causes tuberculosis (TB). Nine million more are
      infected each year. Although extensively drug-resistant TB strains are very rare
      in the U.S., these strains represent a major emerging global public health
      challenge and likely will become more common in the U.S. in coming years.
      Diagnostic imaging plays an integral role in TB diagnosis, screening and control
      efforts, but the risk of occupational infection among radiologic technologists is
      unclear. This article discusses TB epidemiology, diagnosis, prevention, screening
      and treatment, as well as the role of diagnostic imaging.

PMID- 20826600
TI  - Cancer-focused molecular imaging.
AB  - Molecular imaging, based largely on recent advances in genetics, genomics and
      high-throughput computational analysis, uses isotope-labeled probes to target
      specific cell surface molecules, tumor proteins and enzymes. This cross
      disciplinary imaging modality undoubtedly will make profound changes in medical,
      surgical and radiologic practice. Physiology-based imaging modalities naturally
      are relevant for molecular studies. As a relatively new discipline, molecular
      imaging is accompanied by much hope for improved cancer diagnosis and treatment.

PMID- 20826601
TI  - Breast biopsy targeting techniques.
AB  - Knowing how to successfully target small lesions or microcalcifications is
      crucial to breast biopsy success. This article focuses on stereotactic breast
      biopsy, types of imaging systems and biopsy devices and how stereotactic imaging
      targets lesions and adjusts to ensure successful sampling. It also describes
      stereotactic coordinate systems, positioning for patient comfort and ways to
      successfully locate the correct lesion or micro-calcifications. A successful
      biopsy outcome is represented by biopsy of the suspicious area concordant with
      imaging and pathology results. It takes the entire team to achieve this goal.
      This article does not replace official recommendations and practice guidelines
      for breast lesion targeting.

PMID- 20826602
TI  - How to grow a technologist.

PMID- 20826604
TI  - Goniometers.

PMID- 20826603
TI  - Skull fracture diagnosis: a case study.

PMID- 20826605
TI  - Writing conclusions.

PMID- 20826606
TI  - Patient page. Stereotactic breast biopsy.

PMID- 20826607
TI  - Vesicle docking to the spindle pole body is necessary to recruit the exocyst
      during membrane formation in Saccharomyces cerevisiae.
AB  - During meiosis II in Saccharomyces cerevisiae, the cytoplasmic face of the
      spindle pole body, referred to as the meiosis II outer plaque (MOP), is modified
      in both composition and structure to become the initiation site for de novo
      formation of a membrane called the prospore membrane. The MOP serves as a docking
      complex for precursor vesicles that are targeted to its surface. Using
      fluorescence resonance energy transfer analysis, the orientation of coiled-coil
      proteins within the MOP has been determined. The N-termini of two proteins,
      Mpc54p and Spo21p, were oriented toward the outer surface of the structure.
      Mutations in the N-terminus of Mpc54p resulted in a unique phenotype: precursor
      vesicles loosely tethered to the MOP but did not contact its surface. Thus, these
      mpc54 mutants separate the steps of vesicle association and docking. Using these
      mpc54 mutants, we determined that recruitment of the Rab GTPase Sec4p, as well as
      the exocyst components Sec3p and Sec8p, to the precursor vesicles requires
      vesicle docking to the MOP. This suggests that the MOP promotes membrane
      formation both by localization of precursor vesicles to a particular site and by
      recruitment of a second tethering complex, the exocyst, that stimulates
      downstream events of fusion.

PMID- 20826608
TI  - High-resolution whole-genome sequencing reveals that specific chromatin domains
      from most human chromosomes associate with nucleoli.
AB  - The nuclear space is mostly occupied by chromosome territories and nuclear
      bodies. Although this organization of chromosomes affects gene function,
      relatively little is known about the role of nuclear bodies in the organization
      of chromosomal regions. The nucleolus is the best-studied subnuclear structure
      and forms around the rRNA repeat gene clusters on the acrocentric chromosomes. In
      addition to rDNA, other chromatin sequences also surround the nucleolar surface
      and may even loop into the nucleolus. These additional nucleolar-associated
      domains (NADs) have not been well characterized. We present here a whole-genome,
      high-resolution analysis of chromatin endogenously associated with nucleoli. We
      have used a combination of three complementary approaches, namely fluorescence
      comparative genome hybridization, high-throughput deep DNA sequencing and
      photoactivation combined with time-lapse fluorescence microscopy. The data show
      that specific sequences from most human chromosomes, in addition to the rDNA
      repeat units, associate with nucleoli in a reproducible and heritable manner.
      NADs have in common a high density of AT-rich sequence elements, low gene density
      and a statistically significant enrichment in transcriptionally repressed genes.
      Unexpectedly, both the direct DNA sequencing and fluorescence photoactivation
      data show that certain chromatin loci can specifically associate with either the
      nucleolus, or the nuclear envelope.

PMID- 20826609
TI  - Nutrient control of yeast PKA activity involves opposing effects on
      phosphorylation of the Bcy1 regulatory subunit.
AB  - GPB1 and GPB2 encode kelch repeat-containing proteins that regulate protein
      kinase A (PKA) in yeast by a cAMP-independent process. Here we show that Gpb1 and
      Gpb2 stimulate phosphorylation of PKA regulatory subunit Bcy1 in low glucose
      concentrations, thereby promoting the inhibitory function of Bcy1 when nutrients
      are scarce and PKA activity is expected to be low. Gpb1 and Gpb2 stimulate Bcy1
      phosphorylation at an unknown site, and this modification stabilizes Bcy1 that
      has been phosphorylated by PKA catalytic subunits at serine-145. The BCY1(S145A)
      mutation eliminates the effect of gpb1Delta gpb2Delta on Bcy1 stability but
      maintains their effect on phosphorylation and signaling, indicating that
      modulation of PKA activity by Gpb1 and Gpb2 is not solely due to increased levels
      of Bcy1. Inhibition of PKA catalytic subunits that are ATP analog-sensitive
      causes increased Bcy1 phosphorylation at the unknown site in high glucose. When
      PKA is inhibited, gpb1Delta gpb2Delta mutations have no effect on Bcy1
      phosphorylation. Therefore, Gpb1 and Gpb2 oppose PKA activity by blocking the
      ability of PKA to inhibit Bcy1 phosphorylation at a site other than serine-145.
      Stimulation of Bcy1 phosphorylation by Gpb1 and Gpb2 produces a form of Bcy1 that
      is more stable and is a more effective PKA inhibitor.

PMID- 20826610
TI  - Cell type-dependent requirement for PIP box-regulated Cdt1 destruction during S
      phase.
AB  - DNA synthesis-coupled proteolysis of the prereplicative complex component Cdt1 by
      the CRL4(Cdt2) E3 ubiquitin ligase is thought to help prevent rereplication of
      the genome during S phase. To directly test whether CRL4(Cdt2)-triggered
      destruction of Cdt1 is required for normal cell cycle progression in vivo, we
      expressed a mutant version of Drosophila Cdt1 (Dup), which lacks the PCNA-binding
      PIP box (Dup(DeltaPIP)) and which cannot be regulated by CRL4(Cdt2).
      Dup(DeltaPIP) is inappropriately stabilized during S phase and causes
      developmental defects when ectopically expressed. Dup(DeltaPIP) restores DNA
      synthesis to dup null mutant embryonic epidermal cells, but S phase is abnormal,
      and these cells do not progress into mitosis. In contrast, Dup(DeltaPIP)
      accumulation during S phase did not adversely affect progression through follicle
      cell endocycles in the ovary. In this tissue the combination of Dup(DeltaPIP)
      expression and a 50% reduction in Geminin gene dose resulted in egg chamber
      degeneration. We could not detect Dup hyperaccumulation using mutations in the
      CRL4(Cdt2) components Cul4 and Ddb1, likely because these cause pleiotropic
      effects that block cell proliferation. These data indicate that PIP box-mediated
      destruction of Dup is necessary for the cell division cycle and suggest that
      Geminin inhibition can restrain Dup(DeltaPIP) activity in some endocycling cell
      types.

PMID- 20826611
TI  - LPS-induced cytokine production in human dendritic cells is regulated by
      sialidase activity.
AB  - Removal of sialic acid from glycoconjugates on the surface of monocytes enhances
      their response to bacterial LPS. We tested the hypothesis that endogenous
      sialidase activity creates a permissive state for LPS-induced cytokine production
      in human monocyte-derived DCs. Of the four genetically distinct sialidases (Neu1
      4), Neu1, Neu3, and Neu4 are expressed in human monocytes, but only Neu1 and Neu3
      are up-regulated as cells differentiate into DCs. Neu1 and Neu3 are present on
      the surface of monocytes and DCs and are also present intracellularly. DCs
      contain a greater amount of sialic acid than monocytes, but the amount of sialic
      acid/mg total protein declines during differentiation to DCs. This relative
      hyposialylation of cells does not occur in mature DCs grown in the presence of
      zanamivir, a pharmacologic inhibitor of Neu3 but not Neu1, or DANA, an inhibitor
      of Neu1 and Neu3. Inhibition of sialidase activity during differentiation to DCs
      causes no detectable change in cell viability or expression of DC surface
      markers. Differentiation of monocytes into DCs in the presence of zanamivir
      results in reduced LPS- induced expression of IL-6, IL-12p40, and TNF-alpha by
      mature DCs, demonstrating a role for Neu3 in cytokine production. A role for Neu3
      is supported by inhibition of cytokine production by DANA in DCs from Neu1-/- and
      WT mice. We conclude that sialidase-mediated change in sialic acid content of
      specific cell surface glycoconjugates in DCs regulates LPS-induced cytokine
      production, thereby contributing to development of adaptive immune responses.

PMID- 20826612
TI  - Muramyl dipeptide synergizes with Staphylococcus aureus lipoteichoic acid to
      recruit neutrophils in the mammary gland and to stimulate mammary epithelial
      cells.
AB  - Staphylococcus aureus, a major pathogen for the mammary gland of dairy ruminants,
      elicits the recruitment of neutrophils into milk during mastitis, but the
      mechanisms are incompletely understood. We investigated the response of the
      bovine mammary gland to muramyl dipeptide (MDP), an elementary constituent of the
      bacterial peptidoglycan, alone or in combination with lipoteichoic acid (LTA),
      another staphylococcal microbial-associated molecular pattern (MAMP). MDP induced
      a prompt and marked influx of neutrophils in milk, and its combination with LTA
      elicited a more intense and prolonged influx than the responses to either
      stimulus alone. The concentrations of several chemoattractants for neutrophils
      (CXCL1, CXCL2, CXCL3, CXCL8, and C5a) increased in milk after challenge, and the
      highest increases followed challenge with the combination of MDP and LTA. MDP and
      LTA were also synergistic in inducing in vitro chemokine production by bovine
      mammary epithelial cells (bMEpC). Nucleotide-binding oligomerization domain 2
      (NOD2), a major sensor of MDP, was expressed (mRNA) in bovine mammary tissue and
      by bMEpC in culture. The production of interleukin-8 (IL-8) following the
      stimulation of bMEpC by LTA and MDP was dependent on the activation of NF-kappaB.
      LTA-induced IL-8 production did not depend on platelet-activating factor receptor
      (PAFR), as the PAFR antagonist WEB2086 was without effect. In contrast, bMEpC and
      mammary tissue are known to express Toll-like receptor 2 (TLR2) and to respond to
      TLR2 agonists. Although the levels of expression of the inflammatory cytokines
      tumor necrosis factor alpha (TNF-alpha) and IL-1beta were increased by LTA and
      MDP at the mRNA level, no protein could be detected in the bMEpC culture
      supernatant. The level of induction of IL-6 was low at both the mRNA and protein
      levels. These results indicate that MDP and LTA exert synergistic effects to
      induce neutrophilic inflammation in the mammary gland. These results also show
      that bMEpC could contribute to the inflammatory response by recognizing LTA and
      MDP and secreting chemokines but not proinflammatory cytokines. Overall, this
      study indicates that the TLR2 and NOD2 pathways could cooperate to trigger an
      innate immune response to S. aureus mastitis.

PMID- 20826613
TI  - Evaluation of clumping factor A binding region A in a subunit vaccine against
      Staphylococcus aureus-induced mastitis in mice.
AB  - The present study evaluated the potential of recombinant binding region A of
      clumping factor A (rClfA-A) to be an effective component of a vaccine against
      mastitis induced by Staphylococcus aureus in the mouse. rClfA-A and inactivated
      S. aureus were each emulsified in Freund's adjuvant, mineral oil adjuvant, and
      Seppic adjuvant; phosphate-buffered saline was used as a control. Seven groups of
      12 mice each were immunized intraperitoneally three times at 2-week intervals.
      The titers of IgG and subtypes thereof (IgG1 and IgG2a) in the rClfA-A-immunized
      group were more than 1,000-fold higher than those in the killed-bacteria
      immunized group (P < 0.01). Of the three adjuvants used, mineral oil adjuvant
      induced the highest antibody levels for both antigens (P < 0.001). Furthermore,
      the anti-rClfA-A antibody capacities for bacterial adhesion and opsonizing
      phagocytosis were significantly greater in the rClfA-A-immunized group than in
      the killed-bacteria-immunized group (P < 0.05). Lactating mice immunized with
      either rClfA-A or inactivated vaccine were challenged with S. aureus via the
      intramammary route. The numbers of bacteria recovered from the murine mammary
      glands 24 h after inoculation were significantly lower in the rClfA-A group than
      in the killed-bacteria-immunized group (P < 0.001). Histologic examination of the
      mammary glands showed that rClfA-A immunization effectively preserved tissue
      integrity. Thus, rClfA-A emulsified in an oil adjuvant provides strong immune
      protection against S. aureus-induced mastitis in the mouse.

PMID- 20826616
TI  - Digestion and transportation of bovine spongiform encephalopathy-derived prion
      protein in the sheep intestine.
AB  - Bovine spongiform encephalopathy (BSE) is acquired orally and the mechanisms
      involved in the absorption and transportation of infectivity across the gut wall
      are therefore critical. Isolated gut loops were created in lambs, massaged to
      remove intestinal contents (flushed) or left non-flushed, inoculated with cattle
      BSE homogenate and excised at different time-points. Gut loops were examined by
      immunohistochemistry (IHC) for disease-associated prion protein (PrP(d)), and the
      contents were analysed by Western blotting (WB) to determine the degradation rate
      of protease-resistant PrP (PrP(res)). The contents of scrapie-inoculated gut
      loops from a previous experiment were analysed by WB, and these in vivo digestion
      results were compared with those of an in vitro experiment on the same
      transmissible spongiform encephalopathy homogenates. BSE-inoculum-derived PrP(d)
      was detected by IHC in the gut lumen between 15 min and 3.5 h. It was found in
      the intestinal lymphatic system from 30 min onwards and was present at the
      highest frequency at 120 min post-inoculation. In vivo degradation of PrP(res) in
      the BSE inoculum had a significantly (P=0.006) different pattern compared with
      scrapie-derived PrP(res), with the BSE PrP(res) degrading more rapidly. However,
      the overall amount of degradation became similar by 120 min post-challenge. The
      results of the in vitro digestion experiments showed a similar pattern, although
      the magnitude of PrP(res) degradation was less than in the in vivo environment
      where absorption could also take place. BSE-derived PrP(res) is less protease
      resistant than scrapie PrP over a short time-course and the disappearance of
      detectable PrP(res) from the gut lumen results from both absorption and digestion
      by intestinal contents.

PMID- 20826614
TI  - The Th1 immune response to Plasmodium falciparum circumsporozoite protein is
      boosted by adenovirus vectors 35 and 26 with a homologous insert.
AB  - The most advanced malaria vaccine, RTS,S, is comprised of a portion of the
      Plasmodium falciparum circumsporozoite (CS) protein, fused to and admixed with
      the hepatitis B virus surface antigen, and an adjuvant [corrected].This vaccine
      confers short-term protection against malaria infection, with an efficacy of
      about 50%, and induces particularly B-cell and CD4(+) T-cell responses.In the
      present study, we tested the hypothesis that the Th1 immune response to CS
      protein,in particular the CD8(+) T-cell response, which is needed for strong and
      lasting malaria immunity, is boosted to sustainable levels by adenovirus vectors
      35 and 26 with a homologous insert (Ad35.CS/Ad26.CS) [corrected]. In this study,
      we evaluated immune responses induced with vaccination regimens based on an
      adjuvant-containing, yeast-produced complete CS protein followed by two
      recombinant low-seroprevalence adenoviruses expressing P. falciparum CS antigen,
      Ad35.CS (subgroup B) and Ad26.CS (subgroup D). Our results show that (i) the
      yeast (Hansenula polymorpha)produced, adjuvanted full-length CS protein is highly
      potent in inducing high CS-specific humoral responses in mice but produces poor T
      cell responses, (ii) the Ad35.CS vector boosts the gamma interferon-positive (IFN
      gamma(+)) CD8(+) T-cell response induced by the CS protein immunization and
      shifts the immune response toward the Th1 type, and (iii) a three-component
      heterologous vaccination comprised of a CS protein prime followed by boosts with
      Ad35.CS and Ad26.CS elicits an even more robust and sustainable IFN-gamma(+)
      CD8(+) T-cell response than one- or two-component regimens. The Ad35.CS/Ad26.CS
      combination boosted particularly the IFN-gamma(+) and tumor necrosis factor alpha
      positive (TNF-alpha(+)) T cells, confirming the shift of the immune response from
      the Th2 type to the Th1 type. These results support the notion of first
      immunizations of infants with an adjuvanted CS protein vaccine, followed by a
      booster Ad35.CS/Ad26.CS vaccine at a later age, to induce lasting protection
      against malaria for which the Th1 response and immune memory is required.

PMID- 20826615
TI  - New regulatory mechanisms for the intracellular localization and trafficking of
      influenza A virus NS1 protein revealed by comparative analysis of A/PR/8/34 and
      A/Sydney/5/97.
AB  - During influenza A virus infection, the NS1 protein is engaged in different
      functions in different intracellular compartments. In this study, we showed that
      the NS1 of A/PR/8/34 localized in different positions from that of A/Sydney/5/97
      when transiently expressed in Madin-Darby canine kidney cells. Residue 221 of NS1
      was identified to be a new key residue involved in the C-terminal nuclear
      localization signal (NLS) and nucleolar localization signal (NoLS) of NS1 from
      A/Sydney/5/97. Analysis of chimeric NS1 and further mutants showed that residues
      responsible for the binding between NS1 and the cleavage and polyadenylation
      specificity factor (CPSF) are correlated with the intracellular localization of
      transiently expressed NS1 proteins. Fluorescence loss in photobleaching imaging
      revealed that the NS1 protein with both functional NLSs and nuclear export signal
      (NES) was able to shuttle between the nucleus and cytoplasm. Drug inhibition
      experiments and fluorescence resonance energy transfer analysis suggested that
      NS1 was exported out of the cell nuclei via a Crm1-independent pathway. Moreover,
      it is likely that another cytoplasmic localization-related sequence exists in the
      NS1 protein other than the leucine-rich NES. These findings provide new insights
      into the mechanism of intracellular localization and trafficking of influenza A
      virus NS1 protein, which is important for understanding its function.

PMID- 20826617
TI  - Identification and characterization of RNA-binding activity in the ORF1-encoded
      replicase protein of Pelargonium flower break virus.
AB  - Pelargonium flower break virus (PFBV) belongs to the genus Carmovirus (family
      Tombusviridae) and, as with the remaining members of the group, possesses a
      monopartite genome of single-stranded, positive-sense RNA that contains five
      ORFs. The two 5'-proximal ORFs (ORFs 1 and 2) encode two polypeptides of 27 and
      86 kDa (p27 and p86), respectively, that show homology with replication proteins.
      The p27 does not present any motif to explain its presumed involvement in
      replication, while p86 has the motifs conserved in RNA-dependent RNA polymerases.
      In this work, we have confirmed the necessity of p27 and p86 for PFBV
      replication. To gain insights into the function(s) of p27, we have expressed and
      purified the protein from Escherichia coli and tested its ability to bind RNA in
      vitro. The results have shown that p27 is able to bind ssRNA with high affinity
      and in a cooperative fashion and that it is also capable of binding other types
      of nucleic acids, though to a lesser extent. Additionally, competition
      experiments suggest that p27 has a preference for PFBV-derived ssRNAs. Using
      truncated forms of p27, it can be concluded that several regions of the protein
      contribute to its RNA-binding properties and that this contribution is additive.
      This study is the first to show nucleic acid-binding ability of the ORF1 product
      of a carmovirus and the data obtained suggest that this product plays an
      essential role in selection and recruitment of viral RNA replication templates.

PMID- 20826619
TI  - Orf virus cell cycle regulator, PACR, competes with subunit 11 of the anaphase
      promoting complex for incorporation into the complex.
AB  - The poxvirus anaphase promoting complex regulator (PACR) promotes viral
      replication by manipulating the anaphase promoting complex/cyclosome (APC/C), a
      multisubunit ubiquitin ligase complex with essential roles in cell cycle
      regulation. PACR has sequence similarities to APC/C subunit 11 (APC11) and
      associates with APC/C subunits. However, unlike APC11, expression of PACR
      disrupts APC/C functions. Here, we further investigated the interaction of PACR
      with APC/C. Following knockdown of APC1, the subunit linking APC11/APC2 to the
      rest of APC/C, PACR remained bound to APC2 but not to other, distal, subunits of
      the complex, suggesting PACR associates with APC/C via APC2. This was supported
      by the demonstration, in vitro, of a direct interaction between PACR and APC2.
      Moreover, the presence of PACR interfered with interactions between both APC11
      and APC2. Based on these observations we propose that PACR competes with APC11
      for the incorporation into APC/C.

PMID- 20826620
TI  - The cysteine protease domain of porcine reproductive and respiratory syndrome
      virus non-structural protein 2 antagonizes interferon regulatory factor 3
      activation.
AB  - There is growing evidence that porcine reproductive and respiratory syndrome
      virus (PRRSV) has developed mechanisms to subvert the host innate immune
      response. PRRSV non-structural protein 2 (Nsp2) was suggested previously as a
      potential interferon (IFN) antagonist. This study focused on Nsp2 to investigate
      its inhibitory mechanism of IFN induction. It was demonstrated that Nsp2 strongly
      inhibited IFN-beta production by antagonizing activation of the IFN regulatory
      factor 3 (IRF-3) pathway induced by the Sendai virus (SeV). Further studies
      revealed that the cysteine protease domain (PL2) of Nsp2 was necessary for IFN
      antagonism. Additionally, both full-length Nsp2 and the PL2 protease domain of
      Nsp2 were found to inhibit SeV-induced phosphorylation and nuclear translocation
      of IRF-3. These findings suggest that Nsp2 is likely to play an important role in
      subversion of IRF-3-dependent innate antiviral defences, providing a basis for
      elucidating the mechanisms underlying PRRSV pathogenesis.

PMID- 20826618
TI  - Transcription factor Spi-B binds unique sequences present in the tandem repeat
      promoter/enhancer of JC virus and supports viral activity.
AB  - Progressive multifocal leukoencephalopathy (PML) is an often fatal demyelinating
      disease caused by lytic infection of oligodendrocytes with JC virus (JCV). The
      development of PML in non-immunosuppressed individuals is a growing concern with
      reports of mortality in patients treated with mAb therapies. JCV can persist in
      the kidneys, lymphoid tissue and bone marrow. JCV gene expression is restricted
      by non-coding viral regulatory region sequence variation and cellular
      transcription factors. Because JCV latency has been associated with cells
      undergoing haematopoietic development, transcription factors previously reported
      as lymphoid specific may regulate JCV gene expression. This study demonstrates
      that one such transcription factor, Spi-B, binds to sequences present in the JCV
      promoter/enhancer and may affect early virus gene expression in cells obtained
      from human brain tissue. We identified four potential Spi-B-binding sites present
      in the promoter/enhancer elements of JCV sequences from PML variants and the non
      pathogenic archetype. Spi-B sites present in the promoter/enhancers of PML
      variants alone bound protein expressed in JCV susceptible brain and lymphoid
      derived cell lines by electromobility shift assays. Expression of exogenous Spi-B
      in semi- and non-permissive cells increased early viral gene expression.
      Strikingly, mutation of the Spi-B core in a binding site unique to the Mad-4
      variant was sufficient to abrogate viral activity in progenitor-derived
      astrocytes. These results suggest that Spi-B could regulate JCV gene expression
      in susceptible cells, and may play an important role in JCV activity in the
      immune and nervous systems.

PMID- 20826621
TI  - No difference in Gag and Env immune-response profiles between vaccinated and non
      vaccinated rhesus macaques that control immunodeficiency virus replication.
AB  - Recent advances in human immunodeficiency virus (HIV) vaccine design have
      resulted in induction of strong CD4 T-cell proliferative and polyfunctional
      cytokine responses, which are also characteristic for long-term non-progressing
      (LTNP) HIV-infected individuals. However, limited information is available on the
      persistence of these responses after infection. Results from studies in non-human
      primates indicate that vaccine-induced immune responses are partially maintained
      upon viral infection and differ from the responses seen in non-vaccinated animals
      that typically progress to disease. However, it is unclear how these partially
      preserved responses compare to immune responses that are acquired naturally by
      LTNP animals. In this study, immune-response profiles were compared between
      vaccinated animals that, upon SHIV89.6 challenge, became infected but were able
      to control virus replication, and a group of animals having spontaneous control
      of this viral infection. Both groups were found to develop very similar immune
      responses with regard to induction of CD4 and CD8 T-cell polyfunctional cytokine
      responses, proliferative capacity and cytotoxic capacity, as measured by a
      standard 51Cr release assay and more direct ex vivo and in vivo CTL assays.
      Hence, vaccinated animals that become infected, but control infection, appear to
      establish immune responses that are similar to those elicited by long-term non
      progressors.

PMID- 20826623
TI  - Dietary interventions that lower lipoproteins containing apolipoprotein C-III are
      more effective in whites than in blacks: results of the OmniHeart trial.
AB  - BACKGROUND: Blacks have lower average triglyceride and LDL cholesterol
      concentrations than do whites but higher rates of coronary heart disease.
      Apolipoprotein (apo) C-III in VLDL and LDL stimulates atherogenic processes in
      vascular cells. In blacks, the concentration of lipoproteins with apo C-III is
      unknown, and the response to dietary strategies that lower triglyceride and apo C
      III has not been investigated OBJECTIVE: We compared the concentration of and
      dietary effects on apo C-III-containing lipoproteins in blacks and whites.
      DESIGN: In a randomized, 3-period feeding study [OmniHeart (Optimal Macronutrient
      Intake Trial to Prevent Heart Disease)], we measured lipoprotein concentrations
      in 89 blacks and 73 whites who consumed self-selected diets (baseline) and after
      3 healthful diets emphasizing carbohydrate, unsaturated fat, or protein.
      Participants had prehypertension or hypertension, and 79% were overweight or
      obese. RESULTS: While consuming self-selected diets, blacks had lower apo C-III
      in total plasma, VLDL, and LDL than did whites. Unsaturated fat and protein diets
      lowered plasma apo C-III (16% and 18%, respectively) and triglyceride (12% and
      21%, respectively) in whites but not in blacks, reducing racial differences. Most
      important, blacks had a lower concentration of atherogenic LDL with apo C-III at
      baseline and after study diets (34-41% lower, P < 0.02). The molar ratio of apo E
      to apo B was higher in blacks than in whites in total plasma and LDL at baseline
      and after the study diets. CONCLUSIONS: Blacks have lower concentrations of
      atherogenic lipoproteins that contain apo C-III than do whites when consuming
      diverse diets and an attenuated dietary response of triglyceride and apo C-III.
      Dietary efforts to lower triglyceride and apo C-III may be more effective in
      whites than in blacks. The OmniHeart Trial was registered at
      www.clinicaltrials.gov as NCT00051350.

PMID- 20826624
TI  - Total antioxidant capacity of diet in relation to cognitive function and decline.
AB  - BACKGROUND: Epidemiologic evidence on the association of individual antioxidant
      vitamins and cognition is inconsistent. OBJECTIVE: We evaluated the total
      antioxidant capacity of diets on the basis of the ferric-reducing antioxidant
      power (FRAP) assay in relation to cognition in older women. DESIGN: Starting in
      1995, we used a telephone-based cognitive assessment to evaluate cognitive
      function on 3 occasions at 2-y intervals in 16,010 participants aged >=70 y in
      the Nurses' Health Study. In 1980, and every 4 y thereafter, we collected dietary
      information by using a semiquantitative food-frequency questionnaire (FFQ). For
      each participant, we combined FFQ data with food- and supplement-specific FRAP
      values to obtain FRAP scores; these data were averaged from 1980 until the
      initial cognitive interview to reflect long-term diets. We used multivariable
      adjusted linear regression to estimate mean differences in initial cognitive
      function and slopes of decline across quintiles of FRAP scores. RESULTS: In
      multivariable-adjusted models, there was an association between higher total FRAP
      scores and better cognitive function at the first interview (P for trend = 0.003
      for global scores with all cognitive tests combined; mean difference = 0.04
      standard units; 95% CI: 0.01, 0.08 standard units, comparing the highest and
      lowest quintiles). A weaker association was observed for dietary FRAP scores
      (excluding supplements) and initial global scores (P for trend = 0.05). However,
      prospective analyses of cognitive decline indicated no associations with total or
      dietary FRAP scores in models adjusted for multiple potential confounders (P for
      trend = 0.3 and 0.5 for global scores, respectively). CONCLUSION: We observed no
      clear evidence of a consistent association between the total antioxidant capacity
      of diets and cognition in this cohort of older women.

PMID- 20826625
TI  - Coffee, tea, and alcohol intake in relation to risk of type 2 diabetes in African
      American women.
AB  - BACKGROUND: Numerous studies have reported inverse associations of coffee, tea,
      and alcohol intake with risk of type 2 diabetes, but none has reported results
      separately among African American women. OBJECTIVE: We prospectively examined the
      relation of coffee, tea, and alcohol consumption to diabetes risk in African
      American women. DESIGN: The study included 46,906 Black Women's Health Study
      participants aged 30-69 y at baseline in 1995. Dietary intake was assessed in
      1995 and 2001 by using a validated food-frequency questionnaire. During 12 y of
      follow-up, there were 3671 incident cases of type 2 diabetes. Relative risks
      (RRs) and 95% CIs were estimated by using Cox proportional hazards models
      adjusted for diabetes risk factors. RESULTS: Multivariable RRs for intakes of 0
      1, 1, 2-3, and >=4 cups of caffeinated coffee/d relative to no coffee intake were
      0.94 (95% CI: 0.86, 1.04), 0.90 (95% CI: 0.81, 1.01), 0.82 (95% CI: 0.72, 0.93),
      and 0.83 (95% CI: 0.69, 1.01), respectively (P for trend = 0.003). Multivariable
      RRs for intakes of 1-3, 4-6, 7-13, and >=14 alcoholic drinks/wk relative to never
      consumption were 0.90 (95% CI: 0.82, 1.00), 0.68 (95% CI: 0.57, 0.81), 0.78 (95%
      CI: 0.63, 0.96), and 0.72 (95% CI: 0.53, 0.98), respectively (P for trend <
      0.0001). Intakes of decaffeinated coffee and tea were not associated with risk of
      diabetes. CONCLUSION: Our results suggest that African American women who drink
      moderate amounts of caffeinated coffee or alcohol have a reduced risk of type 2
      diabetes.

PMID- 20826626
TI  - Effect of dihydrocapsiate on resting metabolic rate in humans.
AB  - BACKGROUND: Dihydrocapsiate is a capsinoid found in chili peppers.
      Dihydrocapsiate is similar to capsaicin, which is known for its thermogenic
      properties. OBJECTIVE: The objective was to determine the acute and chronic
      effect of dihydrocapsiate on resting metabolic rate (RMR). DESIGN: Seventy-eight
      healthy subjects in a double-blind, parallel-arm trial were randomly assigned to
      3 groups receiving 0 (placebo), 3, or 9 mg dihydrocapsiate/d for 28 d. After a 10
      h overnight fast, RMR was measured by indirect calorimetry for 30 min before and
      120 min after ingestion of dihydrocapsiate. RESULTS: RMR was similar in the 3
      groups before dosing on day 1 [1714 +/- 41 kcal/d (0 mg), 1760 +/- 41 kcal/d (3
      mg), and 1694 +/- 38 kcal/d (9 mg)] and after acute dosing (41 +/- 17, 55 +/- 17,
      and 3 +/- 24 kcal/d for 3-mg, 9-mg, and placebo groups, respectively). When the
      chronic effect of dihydrocapsiate on RMR was calculated from the average 2-h RMR
      on day 28 minus the 30-min preingestion RMR at baseline, a borderline effect in
      subjects receiving 3 mg dihydrocapsiate/d compared with placebo was observed (61
      +/- 24 kcal/d compared with -1 +/- 12 kcal/d, P = 0.054), whereas no significant
      increase in RMR in comparison with placebo was noted for the 9-mg/d dose (48 +/-
      23 kcal/d compared with -1 +/- 12 kcal/d, P = 0.12). When data from both groups
      were combined, the thermic effect of dihydrocapsiate reached significance (53 +/-
      9 kcal/d compared with -1 +/- 12 kcal/d in the placebo group, P = 0.04). Fat
      oxidation was unaffected by dihydrocapsiate. CONCLUSION: After 1 mo of
      supplementation, dihydrocapsiate had a small thermogenic effect of ~50 kcal/d,
      which is in the range of day-to-day RMR variability. This trial was registered at
      clinicaltrials.gov as NCT00999297.

PMID- 20826627
TI  - Mediterranean and carbohydrate-restricted diets and mortality among elderly men:
      a cohort study in Sweden.
AB  - BACKGROUND: Comparative studies on dietary patterns and long-term mortality are
      sparse. OBJECTIVE: The objective was to examine the relations between 10-y
      mortality and adherence to the World Health Organization dietary guidelines
      [Healthy Diet Indicator (HDI)], a Mediterranean-like diet, and a carbohydrate
      restricted (CR) diet in elderly Swedish men. DESIGN: Dietary habits were
      determined by 7-d dietary records in a population-based longitudinal study of 924
      Swedish men (age: 71 +/- 1 y). The HDI score (-1 to 8 points), the Mediterranean
      Diet Score (MDS; 0-8 points), and the CR score (2-20 points) were calculated for
      each participant. Nonadequate reporters of energy intake were identified (n =
      413). Mortality was registered during a median follow-up of 10.2 y. Cox
      proportional hazards regression, with multivariable adjustments, was used to
      determine the effects of adherence to each dietary pattern. RESULTS: Two hundred
      fifteen and 88 subjects died of all-cause and cardiovascular disease,
      respectively. In all individuals, risk relations to mortality for each SD
      increment in the scores were observed for only MDS, with an adjusted hazard ratio
      (HR) of 0.83 (95% CI: 0.70, 0.99). Among adequate dietary reporters (n = 511),
      adjusted HRs for each SD increment in scores were enhanced for MDS (ie, 0.71; 95%
      CI: 0.55, 0.92) for all-cause mortality and 0.63 (95% CI: 0.42, 0.96) for
      cardiovascular mortality. Corresponding HRs for CR diet score were 1.19 (95% CI:
      0.97, 1.45) for all-cause mortality and 1.44 (95% CI: 1.03, 2.02) for
      cardiovascular mortality. CONCLUSION: Adherence to a Mediterranean-like dietary
      pattern reduced mortality, whereas adherence to a CR dietary pattern appeared to
      increase mortality in elderly Swedish men, especially when only adequate dietary
      reporters were considered.

PMID- 20826628
TI  - Relation of omega-3 fatty acid and dietary fish intake with brachial artery flow
      mediated vasodilation in the Multi-Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: The relation between dietary fish intake and brachial artery
      measures, including brachial artery flow-mediated dilation (FMD), has not been
      well established across sex and racial-ethnic groups. OBJECTIVE: We hypothesized
      that consumption of nonfried fish and plasma phospholipid measures of long-chain
      omega-3 (n-3) fatty acids would be positively associated with larger FMD in men
      and women across racial-ethnic groups. DESIGN: We investigated cross-sectional
      associations of brachial artery measures with fish intake (ascertained with a
      food-frequency questionnaire) and plasma phospholipid omega-3 concentrations in
      3045 adults, aged 45-84 y, who were free of clinical cardiovascular disease.
      RESULTS: In overall multivariate-adjusted analyses, there were no significant
      associations between fish intake or any brachial artery measures. However, when
      stratified by sex, there was an association between the highest quartile of
      nonfried fish consumption and a 0.10-mm lower (1 SD) brachial artery diameter in
      men (P = 0.01) and a 0.27% smaller FMD in women (P = 0.02) compared with the
      lowest quartile of nonfried fish intake in each respective sex strata. When
      stratified by race-ethnicity and race-ethnicity by sex, additional heterogeneity
      was noted, but results were difficult to interpret because of small sample sizes.
      Plasma phospholipid omega-3 concentrations showed a similar directionality of
      association with brachial artery measures observed for nonfried fish consumption,
      although statistical significance was not achieved in fully adjusted models.
      CONCLUSION: This study indicates that the association between nonfried fish
      intake and baseline brachial artery size varies by sex, with suggestive evidence
      of sex differences in the association between nonfried fish intake and FMD.

PMID- 20826629
TI  - Nonprescribed physical activity energy expenditure is maintained with structured
      exercise and implicates a compensatory increase in energy intake.
AB  - BACKGROUND: Exercise interventions elicit only modest weight loss, which might
      reflect a compensatory reduction in nonprescribed physical activity energy
      expenditure (PAEE). OBJECTIVE: The objective was to investigate whether there is
      a reduction in nonprescribed PAEE as a result of participation in a 6-mo
      structured exercise intervention in middle-aged men. DESIGN: Sedentary male
      participants [age: 54 +/- 5 y; body mass index (in kg/m2): 28 +/- 3] were
      randomly assigned to a 6-mo progressive exercise (EX) or control (CON) group.
      Energy expenditure during structured exercise (prescribed PAEE) and nonprescribed
      PAEE were determined with the use of synchronized accelerometry and heart rate
      before the intervention, during the intervention (2, 9, and 18 wk), and within a
      2-wk period of detraining after the intervention. RESULTS: Structured prescribed
      exercise increased total PAEE and had no detrimental effect on nonprescribed
      PAEE. Indeed, there was a trend for greater nonprescribed PAEE in the EX group (P
      = 0.09). Weight loss in the EX group (-1.8 +/- 2.2 kg compared with +0.2 +/- 2.2
      kg in the CON group, P < 0.02) reflected only ~40% of the 300-373 kcal/kg body
      mass potential energy deficit from prescribed exercise. Serum leptin
      concentration decreased by 24% in the EX group (compared with 3% in the CON
      group, P < 0.03), and we estimate that this was accompanied by a compensatory
      increase in energy intake of ~100 kcal/d. CONCLUSIONS: The adoption of regular
      structured exercise in previously sedentary, middle-aged, and overweight men does
      not result in a negative compensatory reduction in nonprescribed physical
      activity. The less-than-predicted weight loss is likely to reflect a compensatory
      increase in energy intake in response to a perceived state of relative energy
      insufficiency.

PMID- 20826630
TI  - Fructose and glucose co-ingestion during prolonged exercise increases lactate and
      glucose fluxes and oxidation compared with an equimolar intake of glucose.
AB  - BACKGROUND: When fructose is ingested together with glucose (GLUFRU) during
      exercise, plasma lactate and exogenous carbohydrate oxidation rates are higher
      than with glucose alone. OBJECTIVE: The objective was to investigate to what
      extent GLUFRU increased lactate kinetics and oxidation rate and gluconeogenesis
      from lactate (GNG(L)) and from fructose (GNG(F)). DESIGN: Seven endurance-trained
      men performed 120 min of exercise at ~60% VO2max (maximal oxygen consumption)
      while ingesting 1.2 g glucose/min + 0.8 g of either glucose or fructose/min
      (GLUFRU). In 2 trials, the effects of glucose and GLUFRU on lactate and glucose
      kinetics were investigated with glucose and lactate tracers. In a third trial,
      labeled fructose was added to GLUFRU to assess fructose disposal. RESULTS: In
      GLUFRU, lactate appearance (120 +/- 6 MUmol . kg-1 . min-1), lactate
      disappearance (121 +/- 7 MUmol . kg-1 . min-1), and oxidation (127 +/- 12 MUmol .
      kg-1 . min-1) rates increased significantly (P < 0.001) in comparison with
      glucose alone (94 +/- 16, 95 +/- 16, and 97 +/- 16 MUmol . kg-1 . min-1,
      respectively). GNG(L) was negligible in both conditions. In GLUFRU, GNG(F) and
      exogenous fructose oxidation increased with time and leveled off at 18.8 +/- 3.7
      and 38 +/- 4 MUmol . kg-1 . min-1, respectively, at 100 min. Plasma glucose
      appearance rate was significantly higher (P < 0.01) in GLUFRU (91 +/- 6 MUmol .
      kg-1 . min-1) than in glucose alone (82 +/- 9 MUmol . kg-1 . min-1). Carbohydrate
      oxidation rate was higher (P < 0.05) in GLUFRU. CONCLUSIONS: Fructose increased
      total carbohydrate oxidation, lactate production and oxidation, and GNG(F).
      Fructose oxidation was explained equally by fructose-derived lactate and glucose
      oxidation, most likely in skeletal and cardiac muscle. This trial was registered
      at clinicaltrials.gov as NCT01128647.

PMID- 20826631
TI  - Trends in 24-h urinary sodium excretion in the United States, 1957-2003: a
      systematic review.
AB  - BACKGROUND: Few studies have examined temporal trends in sodium intake in the US
      population. Collections of 24-h urine sodium excretions are reliable markers for
      dietary sodium intake. OBJECTIVE: We examined temporal trends in 24-h urine
      sodium excretions to estimate temporal trends in sodium intake in the US
      population. DESIGN: We performed a systematic search of English-language articles
      in MEDLINE for studies that reported collections of 24-h urine sodium excretions
      in the United States. We estimated mean urine sodium excretions over time for all
      studies and demographic subgroups. RESULTS: We analyzed 38 studies, which dated
      from 1957 to 2003, and estimated a mean (+/- SE) 24-h urine sodium excretion per
      person of 3526 +/- 75 mg Na. In a multivariate random-effects model with study
      year, sex, age, and race, the study year was not associated with any significant
      change in sodium excretions (coefficient = 154 mg Na . 24 h-1 . 10 y-1; 95% CI: 
      140, 448 mg Na . 24 h-1 . 10 y-1). In subgroup analyses, there was no significant
      temporal trend seen in male, female, black, or white study participants.
      CONCLUSION: Sodium intake in the US adult population appears to be well above
      current guidelines and does not appear to have decreased with time.

PMID- 20826632
TI  - Lifestyle counseling and supplementation with flaxseed or walnuts influence the
      management of metabolic syndrome.
AB  - A healthy lifestyle may ameliorate metabolic syndrome (MetS); however, it remains
      unclear if incorporating nuts or seeds into lifestyle counseling (LC) has
      additional benefit. A 3-arm, randomized, controlled trial was conducted among 283
      participants screened for MetS using the updated National Cholesterol Education
      Program Adult Treatment Panel III criteria for Asian Americans. Participants were
      assigned to a LC on the AHA guidelines, LC + flaxseed (30 g/d) (LCF), or LC +
      walnuts (30 g/d) (LCW) group. After the 12-wk intervention, the prevalence of
      MetS decreased significantly in all groups: -16.9% (LC), -20.2% (LCF), and -16.0%
      (LCW). The reversion rate of MetS, i.e. those no longer meeting the MetS criteria
      at 12 wk, was not significantly different among groups (LC group, 21.1%; LCF
      group, 26.6%; and LCW group, 25.5%). However, the reversion rate of central
      obesity was higher in the LCF (19.2%; P = 0.008) and LCW (16.0%; P = 0.04) groups
      than in the LC group (6.3%). Most of the metabolic variables (weight, waist
      circumference, serum glucose, total cholesterol, LDL cholesterol, apolipoprotein
      (Apo) B, ApoE, and blood pressure) were significantly reduced from baseline in
      all 3 groups. However, the severity of MetS, presented as the mean count of MetS
      components, was significantly reduced in the LCW group compared with the LC group
      among participants with confirmed MetS at baseline (P = 0.045). Our results
      suggest that a low-intensity lifestyle education program is effective in MetS
      management. Flaxseed and walnut supplementation may ameliorate central obesity.
      Further studies with larger sample sizes and of longer duration are needed to
      examine the role of these foods in the prevention and management of MetS.

PMID- 20826634
TI  - Potential influence of more-sensitive HIV-1 load detection by the new Roche Cobas
      AmpliPrep/Cobas TaqMan version 2.0 assay on clinical management of HIV-positive
      pregnant women.
AB  - With the introduction of the new Roche Cobas AmpliPrep/Cobas TaqMan version 2.0
      assay, HIV-1 viral loads will be detected more frequently during the peripartum
      period in pregnant HIV-positive women. The implications for the clinical
      management of these patients are discussed in this paper.

PMID- 20826633
TI  - Inulin prolongs survival of intragastrically administered Lactobacillus plantarum
      No. 14 in the gut of mice fed a high-fat diet.
AB  - We tested whether a high-fat diet (HFD) impairs the survival of probiotics in
      mice. In Expt. 1, after feeding either a HFD (62.7% energy) or a normal-fat diet
      (NFD; 11.1% energy) for 2 d, C57BL/6 mice were i.g. administered Lactobacillus
      plantarum No. 14. Fecal recovery of viable L. plantarum was significantly
      decreased 99% by the HFD compared with the NFD. Total bile acid concentrations in
      the small intestine and cecum were significantly higher (1.5- and 2.2-fold of
      NFD, respectively) in mice fed HFD than in those fed NFD. Cholic acid and
      deoxycholic acid significantly reduced the viability of L. plantarum No. 14 in
      culture experiments. In Expt. 2, after feeding HFD for 2 d, simultaneous
      administration of inulin (10 mg) with L. plantarum No. 14 significantly increased
      (100-fold of that without inulin) the fecal recovery of viable L. plantarum.
      Inulin administration did not alter intestinal bile acid concentrations. In Expt.
      3, after feeding HFD for 2 d, mice were i.g. administered either inulin (10 mg)
      or vehicle and, after 6 h, cecal contents were subjected to culture experiments.
      Growth of L. plantarum No. 14 was significantly higher in the cecal contents of
      inulin-administered mice than vehicle-administered mice. Inulin supplementation
      to cecal contents of vehicle-administered mice significantly enhanced the growth
      of L. plantarum No. 14. We propose that HFD impairs the survival of probiotics in
      the gut due to increased bile acid stress and that simultaneous administration of
      inulin prolongs the survival of probiotics in mice fed HFD.

PMID- 20826635
TI  - Microarray for hepatitis B virus genotyping and detection of 994 mutations along
      the genome.
AB  - Genome analysis of hepatitis B virus (HBV) in patient sera is helpful for
      monitoring treatment. We developed an improved version of a DNA microarray to
      identify HBV genotypes and to detect mutations of interest in the S, Pol, Core,
      and X genes. It includes an automated software analysis of fluorescence values
      for simpler, more robust data interpretation. In this version, probes were added
      to identify genotype H, to analyze 155 additional positions, and to detect 561
      additional polymorphisms. Sequences were added to the alignments to resolve
      hybridization problems due to natural polymorphisms in the vicinity of important
      codons. The duplex PCR protocol allowed whole-genome analysis in a single tube.
      An alternative nested-PCR protocol allowed genotyping and mutations in S and
      reverse transcriptase (rt) genes in patients with low viral loads, as
      demonstrated in patients with less than 400 HBV genome copies/ml. Reproducibility
      was high, with variation coefficients lower than 3%. Only 0.57% of 20,771 codons
      from 253 samples could not be identified. The concordance with Sanger sequencing
      for the identification of codons improved from 92.8% to 95.7% with the improved
      version. Concordance was higher than 91% for codons associated with resistance to
      lamivudine, emtricitabine, telbivudine, famciclovir, entecavir, and tenofovir
      with vaccine escape and for pre-Core mutants. Concordance was lower for adefovir
      resistance mutations (68.6%) and mutations in the basal core promoter (60.3%),
      probably because hybridization efficiency was affected by the low GC content of
      the probes. A concordance of 93.7% with sequencing for genotype identification
      was observed in 190 specimens, lower than that obtained with the first version,
      possibly due to mixed virus populations.

PMID- 20826637
TI  - Pseudo-outbreak of adenovirus infection in a neonatal intensive care unit due to
      a false-positive antigen detection test.
AB  - Twenty-eight of 56 infants in a neonatal intensive care unit had stools positive
      for adenovirus by the Sure-Vue adenovirus test. Virus cultures of conventionally
      processed and chloroform-extracted stool samples, as well as conventional and
      real-time PCR tests, were negative for adenovirus. The cause for the 50% false
      positive rate with the antigen test was not determined.

PMID- 20826636
TI  - Nationwide sentinel surveillance of bloodstream Candida infections in 40 tertiary
      care hospitals in Spain.
AB  - Candidemia studies have documented geographic differences in rates and
      epidemiology, underscoring the need for surveillance to monitor trends. We
      conducted prospective candidemia surveillance in Spain to assess the incidence,
      species distribution, frequency of antifungal resistance, and risk factors for
      acquiring a Candida infection. Prospective laboratory-based surveillance was
      conducted from June 2008 to June 2009 in 40 medical centers located around the
      country. A case of candidemia was defined as the isolation of a Candida species
      from a blood culture. Incidence rates were calculated per 1,000 admissions.
      Antifungal susceptibility tests were performed by using broth microdilution assay
      according to the guidelines of the Clinical and Laboratory Standards Institute.
      We detected 984 cases, for an overall incidence of 1.09 cases per 1,000
      admissions. The crude mortality was 20.20%. Candida albicans was the most common
      species (49.08%), followed by C. parapsilosis (20.73%), C. glabrata (13.61%), and
      C. tropicalis (10.77%). Overall, decreased susceptibility to fluconazole occurred
      in 69 (7.01%) incident isolates. Antifungal resistance was rare, and a moderate
      linear correlation between fluconazole and voriconazole MICs was observed. This
      is the largest multicenter candidemia study conducted to date and shows the
      substantial morbidity and mortality of candidemia in Spain.

PMID- 20826638
TI  - Gluconobacter as well as Asaia species, newly emerging opportunistic human
      pathogens among acetic acid bacteria.
AB  - Acetic acid bacteria (AAB) are broadly used in industrial food processing. Among
      them, members of the genera Asaia, Acetobacter, and Granulibacter were recently
      reported to be human opportunistic pathogens. We isolated AAB from clinical
      samples from three patients and describe here the clinical and bacteriological
      features of these cases. We report for the first time (i) the isolation of a
      Gluconobacter sp. from human clinical samples; (ii) the successive isolation of
      different AAB, i.e., an Asaia sp. and two unrelated Gluconobacter spp., from a
      cystic fibrosis patient; and (iii) persistent colonization of the respiratory
      tract by a Gluconobacter sp. in this patient. We reviewed the main clinical
      features associated with AAB isolation identified in the 10 documented reports
      currently available in the literature. Albeit rare, infections as well as
      colonization with AAB are increasingly reported in patients with underlying
      chronic diseases and/or indwelling devices. Clinicians as well as medical
      microbiologists should be aware of these unusual opportunistic pathogens, which
      are difficult to detect during standard medical microbiological investigations
      and which are multiresistant to antimicrobial agents. Molecular methods are
      required for identification of genera of AAB, but the results may remain
      inconclusive for identification to the species level.

PMID- 20826639
TI  - Single-nucleotide polymorphism in the fadD28 gene as a genetic marker for East
      Asia Lineage Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis isolates with a region of difference 105 (RD105)
      deletion, mainly Beijing family spoligotypes, were phylogenetically grouped into
      the East Asia lineage. We identified a single nucleotide polymorphism in codon
      507, ATC to ATT, of the fadD28 gene as a robust marker and developed a rapid
      assay for East Asia lineage M. tuberculosis.

PMID- 20826640
TI  - Detection and identification of Mycobacterium spp. in clinical specimens by
      combining the Roche Cobas Amplicor Mycobacterium tuberculosis assay with
      Mycobacterium genus detection and nucleic acid sequencing.
AB  - We have recently developed a PCR assay for detection of Mycobacterium spp. at the
      genus level based on the Cobas Amplicor platform. The sensitivities for smear
      positive and smear-negative specimens were found to be 100% and 47.9%,
      respectively. The specificity was 97.7%, the positive predictive value 84.6%, and
      the negative predictive value 93.1%. In a follow-up study, we have systematically
      evaluated the Mycobacterium genus assay in parallel with the Cobas Amplicor
      Mycobacterium tuberculosis assay on 2,169 clinical specimens, including
      respiratory and nonrespiratory specimens. Based on the genus assay,
      nontuberculous mycobacteria were readily detected and identified to the species
      level by PCR-mediated sequencing. In addition, our data point to a limited
      specificity of the Cobas Amplicor M. tuberculosis assay.

PMID- 20826641
TI  - Coagulase-negative staphylococcal skin carriage among neonatal intensive care
      unit personnel: from population to infection.
AB  - Coagulase-negative staphylococci (CoNS) are a major cause of sepsis in neonatal
      intensive care units (NICU) worldwide. Infecting strains of these commensal
      bacteria may originate from NICU personnel. Therefore, we studied the
      characteristics of CoNS isolates from NICU personnel and compared them to those
      of isolates from the general population and from sepsis patients. Furthermore, we
      studied the epidemiological effect on CoNS carriage of NICU personnel after a
      period of absence. In our study, we isolated CoNS from the thumbs of NICU
      personnel every 2 weeks during the summer of 2005 and sampled personnel returning
      from vacation and a control group from the general population. Furthermore, we
      collected sepsis isolates from this period. Isolates were tested for antibiotic
      resistance, mecA and icaA carriage, biofilm production, and genetic relatedness.
      We found that mecA and icaA carriage as well as penicillin, oxacillin, and
      gentamicin resistance were significantly more prevalent in CoNS strains from NICU
      personnel than in community isolates. Similar trends were observed when
      postvacation strains were compared to prevacation strains. Furthermore, genetic
      analysis showed that 90% of the blood isolates were closely related to strains
      found on the hands of NICU personnel. Our findings revealed that CoNS carried by
      NICU personnel differ from those in the general population. Hospital strains are
      replaced by community CoNS after a period of absence. NICU personnel are a likely
      cause for the cross-contamination of virulent CoNS that originate from the NICU
      to patients.

PMID- 20826642
TI  - Testing susceptibility of multidrug-resistant Mycobacterium tuberculosis to
      second-line drugs by use of blood agar.
AB  - In this study, the susceptibilities of 35 multidrug-resistant (MDR) Mycobacterium
      tuberculosis clinical isolates to second-line drugs, including kanamycin (KM),
      rifabutin (RBU), ofloxacin (OFX), p-aminosalicylic acid (PAS), capreomycin (CAP),
      clofazimine (CFM), and ethionamide (ETH), were investigated on blood agar
      according to CLSI recommendations. Compared with the results of the Bactec 460 TB
      system, agreement was 100, 100, 97, 100, 100, 100, and 86% for KM, RBU, OFX, PAS,
      CAP, CFM, and ETH, respectively. Compared with the results of the proportion
      method, agreement was 100, 100, 97, 100, 97, 100, and 77% for KM, RBU, OFX, PAS,
      CAP, CFM, and ETH, respectively.

PMID- 20826643
TI  - Novel use of tryptose sulfite cycloserine egg yolk agar for isolation of
      Clostridium perfringens during an outbreak of necrotizing enterocolitis in a
      neonatal unit.
AB  - Clostridium perfringens has been associated with necrotizing enterocolitis (NEC),
      which is a serious disease of neonates. Our study describes the novel use of
      selective tryptose sulfite cycloserine with egg yolk agar (TSC-EYA) during a
      nursery outbreak. This medium provides a rapid, sensitive, and accurate
      presumptive identification of C. perfringens.

PMID- 20826644
TI  - Real-time detection of influenza a, influenza B, and respiratory syncytial virus
      a and B in respiratory specimens by use of nanoparticle probes.
AB  - Seasonal epidemics of influenza and respiratory syncytial virus are responsible
      for significant morbidity and mortality worldwide. Infrequently, novel or
      reemergent strains of influenza A virus have caused rapid, severe global
      pandemics resulting in millions of fatalities. The ability to efficiently and
      accurately detect and differentiate respiratory viruses is paramount for
      effective treatment, infection control, and epidemiological surveillance. We
      evaluated the ability of two FDA-cleared nucleic acid-based tests, the
      semiautomated respiratory virus nucleic acid test (VRNAT) and the fully automated
      respiratory virus nucleic acid test SP (RVNAT(SP)) (Nanosphere Inc., Northbrook,
      IL) to detect influenza A virus, influenza B virus, and respiratory syncytial
      virus A and B (RSV A/B) from clinical nasopharyngeal swab specimens. Detection of
      viral RNA in both tests is based on nucleic acid amplification followed by
      hybridization to capture probes immobilized on a glass slide. A novel technology
      utilizing gold nanoparticle-conjugated probes is utilized to detect the presence
      of captured target DNA. This microarray-based approach to detection has proven to
      be more sensitive than the traditional culture/direct fluorescent-antibody assay
      (DFA) method for detecting RSV and influenza viruses in clinical specimens,
      including the novel 2009 H1N1 strain. Specifically, we report 98.0% sensitivity
      and 96.5% specificity for the VRNAT compared to culture/DFA. Further, the VRNAT
      detected virus in an additional 58% of specimens that were culture negative.
      These data were confirmed using bidirectional sequencing. Evaluation of the fully
      automated RVNAT(SP), which is built on the same detection technology as the VRNAT
      but contains an updated processor enabling complete automation, revealed the two
      tests to be functionally equivalent. Thus, the RVNAT(SP) is a fully automated
      sample-to-result test capable of reliable detection of select respiratory viruses
      directly from clinical specimens in 3.5 h.

PMID- 20826645
TI  - Interlaboratory evaluation of different extraction and real-time PCR methods for
      detection of Coxiella burnetii DNA in serum.
AB  - In the Netherlands, there is an ongoing and unparalleled outbreak of Q fever.
      Rapid and reliable methods to identify patients infected with Coxiella burnetii,
      the causative agent of Q fever, are urgently needed. We evaluated the performance
      of different DNA extraction methods and real-time PCR assays that are in use in
      seven diagnostic or reference laboratories in the Netherlands. A low degree of
      variation in the sensitivities of most of the developed real-time PCR assays was
      observed. However, PCR assays amplifying short DNA fragments yielded better
      results than those producing large DNA fragments. With regard to DNA extraction,
      the automated MagNA Pure Compact system and the manual QIAamp DNA mini kit
      consistently yielded better results than either the MagNA Pure LC system and
      NucliSens EasyMag (both automated) or the High Pure viral nucleic acid kit
      (manual). The present study shows that multiple combinations of DNA extraction
      kits and real-time PCR assays offer equivalent solutions to detect C. burnetii
      DNA in serum samples from patients suspected to have Q fever.

PMID- 20826646
TI  - Molecular evidence of cholera outbreak caused by a toxigenic Vibrio cholerae O1
      El tor variant strain in Kelantan, Malaysia.
AB  - A total of 20 Vibrio cholerae isolates were recovered for investigation from a
      cholera outbreak in Kelantan, Malaysia, that occurred between November and
      December 2009. All isolates were biochemically characterized as V. cholerae
      serogroup O1 Ogawa of the El Tor biotype. They were found to be resistant to
      multiple antibiotics, including tetracycline, erythromycin, sulfamethoxazole
      trimethoprim, streptomycin, penicillin G, and polymyxin B, with 35% of the
      isolates being resistant to ampicillin. All isolates were sensitive to
      ciprofloxacin, norfloxacin, chloramphenicol, gentamicin, and kanamycin. Multiplex
      PCR analysis confirmed the biochemical identification and revealed the presence
      of virulence genes, viz., ace, zot, and ctxA, in all of the isolates.
      Interestingly, the sequencing of the ctxB gene showed that the outbreak strain
      harbored the classical cholera toxin gene and therefore belongs to the newly
      assigned El Tor variant biotype. Clonal analysis by pulsed-field gel
      electrophoresis demonstrated that a single clone of a V. cholerae strain was
      responsible for this outbreak. Thus, we present the first molecular evidence that
      the toxigenic V. cholerae O1 El Tor variant has invaded Malaysia, highlighting
      the need for continuous monitoring to facilitate early interventions against any
      potential epidemic by this biotype.

PMID- 20826647
TI  - Death by edible mushroom: first report of Volvariella volvacea as an etiologic
      agent of invasive disease in a patient following double umbilical cord blood
      transplantation.
AB  - We describe a case of invasive fungal infection caused by Volvariella volvacea
      following double umbilical cord blood transplantation (UCBT). Although infections
      caused by several mushroom species have been documented, we believe this to be
      the first published report of invasive infection with Volvariella volvacea, an
      edible mushroom belonging to Agaricales.

PMID- 20826648
TI  - Bacterial 16S sequence analysis of severe caries in young permanent teeth.
AB  - Previous studies have confirmed the association of the acid producers
      Streptococcus mutans and Lactobacillus spp. with childhood caries, but they also
      suggested these microorganisms are not sufficient to explain all cases of caries.
      In addition, health-associated bacterial community profiles are not well
      understood, including the importance of base production and acid catabolism in pH
      homeostasis. The bacterial community composition in health and in severe caries
      of the young permanent dentition was compared using Sanger sequencing of the
      ribosomal 16S rRNA genes. Lactobacillus species were dominant in severe caries,
      and levels rose significantly as caries progressed from initial to deep lesions.
      S. mutans was often observed at high levels in the early stages of caries but
      also in some healthy subjects and was not statistically significantly associated
      with caries progression in the overall model. Lactobacillus or S. mutans was
      found either at low levels or not present in several samples. Other potential
      acid producers observed at high levels in these subjects included strains of
      Selenomonas, Neisseria, and Streptococcus mitis. Propionibacterium FMA5 was
      significantly associated with caries progression but was not found at high
      levels. An overall loss of community diversity occurred as caries progressed, and
      species that significantly decreased included the Streptococcus mitis-S.
      pneumoniae-S. infantis group, Corynebacterium matruchotii, Streptococcus
      gordonii, Streptococcus cristatus, Capnocytophaga gingivalis, Eubacterium IR009,
      Campylobacter rectus, and Lachnospiraceae sp. C1. The relationship of acid-base
      metabolism to 16S rRNA gene-based species assignments appears to be complex, and
      metagenomic approaches that would allow functional profiling of entire genomes
      will be helpful in elucidating the microbial pathogenesis of caries.

PMID- 20826649
TI  - High prevalence of clarithromycin resistance and cagA, vacA, iceA2, and babA2
      genotypes of Helicobacter pylori in Brazilian children.
AB  - We isolated 45 Helicobacter pylori strains from 217 child patients. Resistance to
      clarithromycin, metronidazole, amoxicillin, and tetracycline was detected in 27%,
      13%, 4%, and 0% of strains, respectively. The A2143G mutation was the most
      prevalent (67%) among clarithromycin-resistant strains. In addition, strain
      genotyping revealed a significant association between gastritis severity and the
      simultaneous presence of cagA, vacA s1m1, iceA2, and babA2 genes.

PMID- 20826650
TI  - Multicenter evaluation of the BD Max GBS assay for detection of group B
      streptococci in prenatal vaginal and rectal screening swab specimens from
      pregnant women.
AB  - A new integrated extraction and real-time PCR-based system for the detection of
      group B streptococci in antepartum screening samples enriched in Lim broth was
      compared to the CDC-recommended culture method. The BD Max GBS assay exhibited
      acceptable sensitivity (95%) and specificity (96.7%) compared to those of the
      culture method in this multisite evaluation.

PMID- 20826652
TI  - Is PrPC a mediator of Abeta toxicity in Alzheimer's disease?

PMID- 20826651
TI  - Human immunodeficiency virus type 1 protease inhibitor drug-resistant mutants
      give discordant results when compared in single-cycle and multiple-cycle fitness
      assays.
AB  - The replication fitness of HIV-1 drug-resistant mutants has been measured using
      either multiple-cycle or single-cycle assays (MCAs or SCAs); these assays have
      not been systematically compared. We developed an MCA and an SCA that utilized
      either intact or env-deleted recombinant viral vectors, respectively, in which
      virus-infected cells were detected by flow cytometry of a reporter gene product.
      Fitness was measured using each assay for 11 protease mutants, 9 reverse
      transcriptase mutants, and two mutants with mutations in gag p6, which is
      important for the release of virus particles from the cell membrane. In the SCA,
      fitness (replication capacity [RC]) was defined as the proportion of cells
      infected by the mutant compared to the wild type 40 h after infection. MCA
      fitness (1+s) was determined by comparing the changes in the relative proportions
      of cells infected by the mutant and the wild type between 3 and 5 days after
      infection. Five protease mutants showed statistically different fitness values by
      the MCA versus the SCA: the D30N, G48V, I50V, I54L, and I54M mutants. When all
      the mutants were ranked in order from most to least fit for both assays, 4
      protease mutants moved more than 5 positions in rank: the D30N, I54L, I54M, and
      V82A mutants. There were no significant differences in fitness for the gag p6 or
      reverse transcriptase mutants. We propose that discordant results in the MCA and
      SCA are due to alterations in late events in the virus life cycle that are not
      captured in an SCA, such as burst size, cell-to-cell transmission, or infected
      cell life span.

PMID- 20826653
TI  - Nanodomain control of exocytosis is responsible for the signaling capability of a
      retinal ribbon synapse.
AB  - Primary sensory circuits encode both weak and intense stimuli reliably, requiring
      that their synapses signal over a wide dynamic range. In the retinal circuitry
      subserving night vision, processes intrinsic to the rod bipolar (RB) cell
      presynaptic active zone (AZ) permit the RB synapse to encode signals generated by
      the absorption of single photons as well as by more intense stimuli. In a study
      using an in vitro slice preparation of the mouse retina, we provide evidence that
      the location of Ca channels with low open probability within nanometers of the
      release sites is a critical determinant of the physiological behavior of the RB
      synapse. This gives rise to apparent one-to-one coupling between Ca channel
      opening and vesicle release, allowing presynaptic potential to be encoded
      linearly over a wide dynamic range. Further, it permits a transition from
      univesicular to multivesicular release (MVR) when two Ca channels/AZ open at
      potentials above the threshold for exocytosis. MVR permits small presynaptic
      voltage changes to elicit postsynaptic responses larger than quantal synaptic
      noise.

PMID- 20826654
TI  - Activation of the liver X receptor increases neuroactive steroid levels and
      protects from diabetes-induced peripheral neuropathy.
AB  - Neuroactive steroids act in the peripheral nervous system as physiological
      regulators and as protective agents for acquired or inherited peripheral
      neuropathy. In recent years, modulation of neuroactive steroids levels has been
      studied as a potential therapeutic approach to protect peripheral nerves from
      damage induced by diabetes. Nuclear receptors of the liver X receptor (LXR)
      family regulate adrenal steroidogenesis via their ability to control cholesterol
      homeostasis. Here we show that rat sciatic nerve expresses both LRXalpha and beta
      isoforms and that these receptors are functional. Activation of liver X receptors
      using a synthetic ligand results in increased levels of neurosteroids and
      protection of the sciatic nerve from neuropathy induced by diabetes. LXR ligand
      treatment of streptozotocin-treated rats increases expression in the sciatic
      nerve of steroidogenic acute regulatory protein (a molecule involved in the
      transfer of cholesterol into mitochondria), of the enzyme P450scc (responsible
      for conversion of cholesterol into pregnenolone), of 5alpha-reductase (an enzyme
      involved in the generation of neuroactive steroids) and of classical LXR targets
      involved in cholesterol efflux, such as ABCA1 and ABCG1. These effects were
      associated with increased levels of neuroactive steroids (e.g., pregnenolone,
      progesterone, dihydroprogesterone and 3alpha-diol) in the sciatic nerve, and with
      neuroprotective effects on thermal nociceptive activity, nerve conduction
      velocity, and Na(+), K(+)-ATPase activity. These results suggest that LXR
      activation may represent a new pharmacological avenue to increase local
      neuroactive steroid levels that exert neuroprotective effects in diabetic
      neuropathy.

PMID- 20826655
TI  - Early B-cell factors are required for specifying multiple retinal cell types and
      subtypes from postmitotic precursors.
AB  - The establishment of functional retinal circuits in the mammalian retina depends
      critically on the proper generation and assembly of six classes of neurons, five
      of which consist of two or more subtypes that differ in morphologies,
      physiological properties, and/or sublaminar positions. How these diverse neuronal
      types and subtypes arise during retinogenesis still remains largely to be defined
      at the molecular level. Here we show that all four family members of the early B
      cell factor (Ebf) helix-loop-helix transcription factors are similarly expressed
      during mouse retinogenesis in several neuronal types and subtypes including
      ganglion, amacrine, bipolar, and horizontal cells, and that their expression in
      ganglion cells depends on the ganglion cell specification factor Brn3b.
      Misexpressed Ebfs bias retinal precursors toward the fates of non-AII glycinergic
      amacrine, type 2 OFF-cone bipolar and horizontal cells, whereas a dominant
      negative Ebf suppresses the differentiation of these cells as well as ganglion
      cells. Reducing Ebf1 expression by RNA interference (RNAi) leads to an inhibitory
      effect similar to that of the dominant-negative Ebf, effectively neutralizes the
      promotive effect of wild-type Ebf1, but has no impact on the promotive effect of
      an RNAi-resistant Ebf1. These data indicate that Ebfs are both necessary and
      sufficient for specifying non-AII glycinergic amacrine, type 2 OFF-cone bipolar
      and horizontal cells, whereas they are only necessary but not sufficient for
      specifying ganglion cells; and further suggest that Ebfs may coordinate and
      cooperate with other retinogenic factors to ensure proper specification and
      differentiation of diverse retinal cell types and subtypes.

PMID- 20826656
TI  - Induced loss of ADAR2 engenders slow death of motor neurons from Q/R site
      unedited GluR2.
AB  - GluR2 is a subunit of the AMPA receptor, and the adenosine for the Q/R site of
      its pre-mRNA is converted to inosine (A-to-I conversion) by the enzyme called
      adenosine deaminase acting on RNA 2 (ADAR2). Failure of A-to-I conversion at this
      site affects multiple AMPA receptor properties, including the Ca(2+) permeability
      of the receptor-coupled ion channel, thereby inducing fatal epilepsy in mice
      (Brusa et al., 1995; Feldmeyer et al., 1999). In addition, inefficient GluR2 Q/R
      site editing is a disease-specific molecular dysfunction found in the motor
      neurons of sporadic amyotrophic lateral sclerosis (ALS) patients (Kawahara et
      al., 2004). Here, we generated genetically modified mice (designated as AR2) in
      which the ADAR2 gene was conditionally targeted in motor neurons using the
      Cre/loxP system. These AR2 mice showed a decline in motor function commensurate
      with the slow death of ADAR2-deficient motor neurons in the spinal cord and
      cranial motor nerve nuclei. Notably, neurons in nuclei of oculomotor nerves,
      which often escape degeneration in ALS, were not decreased in number despite a
      significant decrease in GluR2 Q/R site editing. All cellular and phenotypic
      changes in AR2 mice were prevented when the mice carried endogenous GluR2 alleles
      engineered to express edited GluR2 without ADAR2 activity (Higuchi et al., 2000).
      Thus, loss of ADAR2 activity causes AMPA receptor-mediated death of motor
      neurons.

PMID- 20826657
TI  - The role of contralesional dorsal premotor cortex after stroke as studied with
      concurrent TMS-fMRI.
AB  - Contralesional dorsal premotor cortex (cPMd) may support residual motor function
      following stroke. We performed two complementary experiments to explore how cPMd
      might perform this role in a group of chronic human stroke patients. First, we
      used paired-coil transcranial magnetic stimulation (TMS) to establish the
      physiological influence of cPMd on ipsilesional primary motor cortex (iM1) at
      rest. We found that this influence became less inhibitory/more facilitatory in
      patients with greater clinical impairment. Second, we applied TMS over cPMd
      during functional magnetic resonance imaging (fMRI) in these patients to examine
      the causal influence of cPMd TMS on the whole network of surviving cortical motor
      areas in either hemisphere and whether these influences changed during affected
      hand movement. We confirmed that hand grip-related activation in cPMd was greater
      in more impaired patients. Furthermore, the peak ipsilesional sensorimotor cortex
      activity shifted posteriorly in more impaired patients. Critical new findings
      were that concurrent TMS-fMRI results correlated with the level of both clinical
      impairment and neurophysiological impairment (i.e., less inhibitory/more
      facilitatory cPMd-iM1 measure at rest as assessed with paired-coil TMS).
      Specifically, greater clinical and neurophysiological impairment was associated
      with a stronger facilitatory influence of cPMd TMS on blood oxygenation level
      dependent signal in posterior parts of ipsilesional sensorimotor cortex during
      hand grip, corresponding to the posteriorly shifted sensorimotor activity seen in
      more impaired patients. cPMd TMS was not found to influence activity in other
      brain regions in either hemisphere. This state-dependent influence on
      ipsilesional sensorimotor regions may provide a mechanism by which cPMd supports
      recovered function after stroke.

PMID- 20826658
TI  - Abeta oligomers cause localized Ca(2+) elevation, missorting of endogenous Tau
      into dendrites, Tau phosphorylation, and destruction of microtubules and spines.
AB  - Aggregation of amyloid-beta (Abeta) and Tau protein are hallmarks of Alzheimer's
      disease (AD), and according to the Abeta-cascade hypothesis, Abeta is considered
      toxic for neurons and Tau a downstream target of Abeta. We have investigated
      differentiated primary hippocampal neurons for early localized changes following
      exposure to Abeta oligomers. Initial events become evident by missorting of
      endogenous Tau into the somatodendritic compartment, in contrast to axonal
      sorting in normal neurons. In missorted dendritic regions there is a depletion of
      spines and local increase in Ca(2+), and breakdown of microtubules. Tau in these
      regions shows elevated phosphorylation at certain sites diagnostic of AD-Tau
      (e.g., epitope of antibody 12E8, whose phosphorylation causes detachment of Tau
      from microtubules, and AT8 epitope), and local elevation of certain kinase
      activities (e.g., MARK/par-1, BRSK/SADK, p70S6K, cdk5, but not GSK3beta, JNK,
      MAPK). These local effects occur without global changes in Tau, tubulin, or
      kinase levels. Somatodendritic missorting occurs not only with Tau, but also with
      other axonal proteins such as neurofilaments, and correlates with pronounced
      depletion of microtubules and mitochondria. The Abeta-induced effects on
      microtubule and mitochondria depletion, Tau missorting, and loss of spines are
      prevented by taxol, indicating that Abeta-induced microtubule destabilization and
      corresponding traffic defects are key factors in incipient degeneration. By
      contrast, the rise in Ca(2+) levels, kinase activities, and Tau phosphorylation
      cannot be prevented by taxol. Incipient and local changes similar to those of
      Abeta oligomers can be evoked by cell stressors (e.g., H(2)O(2), glutamate, serum
      deprivation), suggesting some common mechanism of signaling.

PMID- 20826660
TI  - Distinct retinal deficits in a zebrafish pyruvate dehydrogenase-deficient mutant.
AB  - Mutations in ubiquitously expressed metabolic genes often lead to CNS-specific
      effects, presumably because of the high metabolic demands of neurons. However,
      mutations in omnipresent metabolic pathways can conceivably also result in cell
      type-specific effects because of cell-specific requirements for intermediate
      products. One such example is the zebrafish noir mutant, which we found to be
      mutated in the pdhb gene, coding for the E1 beta subunit of the pyruvate
      dehydrogenase complex. This vision mutant is described as blind and was isolated
      because of its vision defect-related darker appearance. A detailed morphological,
      behavioral, and physiological analysis of the phenotype revealed an unexpected
      specific effect on the retina. Surprisingly, the cholinergic amacrine cells of
      the inner retina are affected earlier than the photoreceptors. This might be
      attributable to the inability of these cells to maintain production of their
      neurotransmitter acetylcholine. This is reflected in an earlier loss of motion
      vision, followed only later by a general loss of light perception. Since both
      characteristics of the phenotype are attributable to a loss of acetyl-CoA
      production by pyruvate dehydrogenase, we used a ketogenic diet to bypass this
      metabolic block and could indeed partially rescue vision and prolong survival of
      the larvae. The noir mutant provides a case for a systemic disease with ocular
      manifestation with a surprising specific effect on the retina given the
      ubiquitous requirement for the mutated gene.

PMID- 20826659
TI  - In vivo development of outer retinal synapses in the absence of glial contact.
AB  - Astroglia secrete factors that promote synapse formation and maintenance. In
      culture, glial contact has also been shown to facilitate synaptogenesis. Here, we
      examined whether glial contact is important for establishing circuits in vivo by
      simultaneously monitoring differentiation of glial cells and local synaptogenesis
      over time. Photoreceptor circuits of the vertebrate retina are particularly
      suitable for this study because of the relatively simple, laminar organization of
      their connectivity with their target neurons, horizontal cells and bipolar cells.
      Also, individual photoreceptor terminals are ensheathed within the outer
      plexiform layer (OPL) by the processes of one type of glia, Muller glia cells
      (MGs). We conducted in vivo time-lapse multiphoton imaging of the rapidly
      developing and relatively transparent zebrafish retina to ascertain the time
      course of MG development relative to OPL synaptogenesis. The emergence of
      synaptic triads, indicative of functional photoreceptor circuits, and structural
      association with glial processes were also examined across ages by electron
      microscopy. We first show that MG processes form territories that tile within the
      inner and outer synaptic layers. We then demonstrate that cone photoreceptor
      synapses are assembled before the elaboration of MG processes in the OPL. Using a
      targeted cell ablation approach, we also determined whether the maintenance of
      photoreceptor synapses is perturbed when local MGs are absent. We found that
      removal of MGs had no appreciable effect on the stability of newly formed cone
      synapses. Thus, in contrast to other CNS circuits, contact from glia is not
      necessary for the formation or immediate stabilization of outer retinal synapses.

PMID- 20826661
TI  - Incentive learning underlying cocaine-seeking requires mGluR5 receptors located
      on dopamine D1 receptor-expressing neurons.
AB  - Understanding the psychobiological basis of relapse remains a challenge in
      developing therapies for drug addiction. Relapse in cocaine addiction often
      occurs following exposure to environmental stimuli previously associated with
      drug taking. The metabotropic glutamate receptor, mGluR5, is potentially
      important in this respect; it plays a central role in several forms of striatal
      synaptic plasticity proposed to underpin associative learning and memory
      processes that enable drug-paired stimuli to acquire incentive motivational
      properties and trigger relapse. Using cell type-specific RNA interference, we
      have generated a novel mouse line with a selective knock-down of mGluR5 in
      dopamine D1 receptor-expressing neurons. Although mutant mice self-administer
      cocaine, we show that reinstatement of cocaine-seeking induced by a cocaine
      paired stimulus is impaired. By examining different aspects of associative
      learning in the mutant mice, we identify deficits in specific incentive learning
      processes that enable a reward-paired stimulus to directly reinforce behavior and
      to become attractive, thus eliciting approach toward it. Our findings show that
      glutamate signaling through mGluR5 located on dopamine D1 receptor-expressing
      neurons is necessary for incentive learning processes that contribute to cue
      induced reinstatement of cocaine-seeking and which may underpin relapse in drug
      addiction.

PMID- 20826662
TI  - Proline-rich tyrosine kinase 2 regulates hippocampal long-term depression.
AB  - Proline-rich tyrosine kinase 2 (PYK2), also known as cell adhesion kinase beta or
      protein tyrosine kinase 2b, is a calcium-dependent signaling protein involved in
      cell migration. Phosphorylation of residue Y402 is associated with activation of
      PYK2 and leads to the recruitment of downstream signaling molecules. PYK2 was
      previously implicated in long-term potentiation (LTP); however, the role of PYK2
      in long-term depression (LTD) is unknown. Here, we report that PYK2 is activated
      by NMDA receptor stimulation (chemical LTD) in cultured neurons. Small hairpin
      RNA-mediated knockdown of PYK2 blocks LTD, but not LTP, in hippocampal slice
      cultures. We find that the Y402 residue and, to a lesser extent, PYK2 kinase
      activity contribute to PYK2's role in LTD. Knockdown experiments indicate that
      PYK2 is required to suppress NMDA-induced extracellular signal-regulated kinase
      (ERK) phosphorylation. Overexpression of PYK2 depresses NMDA-induced ERK
      phosphorylation and inhibits LTP, but not LTD. Our data indicate that PYK2 is
      critical for the induction of LTD, possibly in part by antagonizing ERK signaling
      in hippocampal neurons.

PMID- 20826663
TI  - Multivesicular release differentiates the reliability of synaptic transmission
      between the visual cortex and the somatosensory cortex.
AB  - Neurons in layer 4 (L4) of the cortex play an important role in transferring
      signals from thalamus to other layers of the cortex. Understanding the
      fundamental properties of synaptic transmission between L4 neurons helps us gain
      a clear picture of how the neuronal network in L4 cooperates to process sensory
      information. In the present study, we have determined the underlying parameters
      that govern synaptic strength, such as quantal size, size of readily releasable
      vesicle pool, and release probability (Pr) of excitatory synaptic connections
      within L4 of the visual cortex (V1) and the somatosensory cortex (S1) in mice.
      Although only a single vesicle is released per release site under physiological
      conditions at V1 synapses, multivesicular release (MVR) is observed at S1
      synapses. In addition, we observed a saturation of postsynaptic receptors at S1
      synapses. Other synaptic properties are similar in both cortices. Dynamic clamp
      experiments suggest that higher Pr and MVR at S1 synapses lower the requirement
      of the number of synaptic inputs to generate postsynaptic action potentials. In
      addition, the slower decay of synaptic current and the intrinsic membrane
      properties of the postsynaptic neuron also contribute to the reliable
      transmission between S1 neurons.

PMID- 20826664
TI  - Reduced survival of motor neuron (SMN) protein in motor neuronal progenitors
      functions cell autonomously to cause spinal muscular atrophy in model mice
      expressing the human centromeric (SMN2) gene.
AB  - Spinal muscular atrophy (SMA) is a common (approximately 1:6400) autosomal
      recessive neuromuscular disorder caused by a paucity of the survival of motor
      neuron (SMN) protein. Although widely recognized to cause selective spinal motor
      neuron loss when deficient, the precise cellular site of action of the SMN
      protein in SMA remains unclear. In this study we sought to determine the
      consequences of selectively depleting SMN in the motor neurons of model mice.
      Depleting but not abolishing the protein in motor neuronal progenitors causes an
      SMA-like phenotype. Neuromuscular weakness in the model mice is accompanied by
      peripheral as well as central synaptic defects, electrophysiological
      abnormalities of the neuromuscular junctions, muscle atrophy, and motor neuron
      degeneration. However, the disease phenotype is more modest than that observed in
      mice expressing ubiquitously low levels of the SMN protein, and both symptoms as
      well as early electrophysiological abnormalities that are readily apparent in
      neonates were attenuated in an age-dependent manner. We conclude that selective
      knock-down of SMN in motor neurons is sufficient but may not be necessary to
      cause a disease phenotype and that targeting these cells will be a requirement of
      any effective therapeutic strategy. This realization is tempered by the
      relatively mild SMA phenotype in our model mice, one explanation for which is the
      presence of normal SMN levels in non-neuronal tissue that serves to modulate
      disease severity.

PMID- 20826665
TI  - Delays conferred by escalating costs modulate dopamine release to rewards but not
      their predictors.
AB  - Efficient reward seeking is essential for survival and invariably requires
      overcoming costs, such as physical effort and delay, which are constantly
      changing in natural settings. Dopamine transmission has been implicated in
      decisions weighing the benefits and costs of obtaining a reward, but it is still
      unclear how dynamically changing effort and delay costs affect dopamine signaling
      to rewards and related stimuli. Using fast-scan cyclic voltammetry, we examined
      phasic dopamine release in the nucleus accumbens (NAcc) core and shell during
      reward-seeking behavior in rats. To manipulate the effort and time needed to earn
      a reward, we used instrumental tasks in which the response requirements (number
      of lever presses) were either fixed throughout a behavioral session [fixed ratio
      (FR)] or systematically increased from trial to trial [progressive ratio (PR)].
      Dopamine release evoked by cues denoting reward availability was no different
      between these conditions, indicating insensitivity to escalating effort or delay
      costs. In contrast, dopamine release to reward delivery in both the NAcc core and
      shell increased in PR, but not in FR, sessions. This enhancement of reward-evoked
      dopamine signaling was also observed in sessions in which the response
      requirement was fixed but the delay to reward delivery increased, yoked to
      corresponding trials in PR sessions. These findings suggest that delay, and not
      effort, was principally responsible for the increased reward-evoked dopamine
      release in PR sessions. Together, these data demonstrate that NAcc dopamine
      release to rewards and their predictors are dissociable and differentially
      regulated by the delays conferred under escalating costs.

PMID- 20826666
TI  - A single seizure episode leads to rapid functional activation of KCC2 in the
      neonatal rat hippocampus.
AB  - Functional expression of the K-Cl cotransporter KCC2 in developing central
      neurons is crucial for the maturation of Cl(-)-dependent, GABA(A) receptor
      mediated inhibitory responses. In pyramidal neurons of the rodent hippocampus,
      GABAergic postsynaptic responses are typically depolarizing and often excitatory
      during the first postnatal week. Here, we show that a single neonatal seizure
      episode induced by kainate injection during postnatal days 5-7 results in a fast
      increase in the Cl(-) extrusion capacity of rat hippocampal CA1 neurons, with a
      consequent hyperpolarizing shift of the reversal potential of GABA(A)-mediated
      currents (E(GABA)). A significant increase in the surface expression of KCC2 as
      well as the alpha2 subunit of the Na-K-ATPase parallels the seizure-induced
      increase in the Cl(-) extrusion capacity. Exposing hippocampal slices to kainate
      resulted in a similar increase in the neuronal Cl(-) extrusion and in the surface
      expression of KCC2. Both effects were blocked by the kinase inhibitor K252a.
      Hence, in the neonatal hippocampus the overall KCC2 expression level is high
      enough to promote a rapid functional activation of K-Cl cotransport and a
      consequent negative shift in E(GABA) close to the adult level. The activity
      dependent regulation of KCC2 function and its effect on GABAergic transmission
      may represent an intrinsic antiepileptogenic mechanism.

PMID- 20826667
TI  - Pyramidal neurons are generated from oligodendroglial progenitor cells in adult
      piriform cortex.
AB  - Previous studies have shown that oligodendroglial progenitor cells (OPCs) can
      give rise to neurons in vitro and in perinatal cerebral cortex in vivo. We now
      report that OPCs in adult murine piriform cortex express low levels of
      doublecortin, a marker for migratory and immature neurons. Additionally, these
      OPCs express Sox2, a neural stem cell marker, and Pax6, a transcription factor
      characteristic of progenitors for cortical glutamatergic neurons. Genetic fate
      mapping by means of an inducible Cre-LoxP recombination system proved that these
      OPCs differentiate into pyramidal glutamatergic neurons in piriform cortex.
      Several lines of evidence indicated that these newly formed neurons became
      functionally integrated into the cortical neuronal network. Our data suggest that
      NG2(+)/PDGFRalpha(+) proteolipid protein promoter-expressing progenitors generate
      pyramidal glutamatergic neurons within normal adult piriform cortex.

PMID- 20826668
TI  - The germinal zones of the basal ganglia but not the septum generate GABAergic
      interneurons for the cortex.
AB  - Cortical interneurons originate from subpallial precursors and migrate into the
      cortex during development. Using genetic lineage tracing in transgenic mice we
      examine the contribution of two germinal zones, the septum and the lateral
      ganglionic eminence/caudal ganglionic eminence (LGE/CGE) to interneurons of the
      cortex. We find that the septal neuroepithelium does not generate interneurons
      for the neocortex. There is, however, clear migration of cells from the LGE/CGE
      to the cortex. Comparison of the dynamics of cortical colonization by the two
      major cohorts of interneurons originating in the medial ganglionic eminence (MGE)
      and the LGE/CGE has shown differences in the timing of migration and initial
      route of entry into the cortex. LGE/CGE-derived interneurons enter the cortex
      later than the MGE-derived ones. They invade the cortex through the
      subventricular/intermediate zone route and only later disperse within the
      cortical plate and the marginal zone. During the first postnatal week MGE
      interneurons move extensively to acquire their laminar position within the
      cortical plate whereas LGE/CGE-derived cells remain largely within the upper
      layers of the cortex. The two populations intermingle in the adult cortex but
      have distinct neurochemical properties and different overall distributions.
      LGE/CGE-derived interneurons account for one third of the total GABAergic
      interneuron population in the adult cortex.

PMID- 20826669
TI  - Dynamic spike thresholds during synaptic integration preserve and enhance
      temporal response properties in the avian cochlear nucleus.
AB  - Neurons of the cochlear nuclei are anatomically and physiologically specialized
      to optimally encode temporal and spectral information about sound stimuli, in
      part for binaural auditory processing. The avian cochlear nucleus magnocellularis
      (NM) integrates excitatory eighth nerve inputs and depolarizing GABAergic
      inhibition such that temporal fidelity is enhanced across the synapse. The
      biophysical mechanisms of this depolarizing inhibition, and its role in temporal
      processing, are not fully understood. We used whole-cell electrophysiology and
      computational modeling to examine how subthreshold excitatory inputs are
      integrated and how depolarizing IPSPs affect spike thresholds and synaptic
      integration by chick NM neurons. We found that both depolarizing inhibition and
      subthreshold excitatory inputs cause voltage threshold accommodation, nonlinear
      temporal summation, and shunting. Inhibition caused such large changes in
      threshold that subthreshold excitatory inputs were followed by a refractory
      period. We hypothesize that these large shifts in threshold eliminate spikes to
      asynchronous inputs, providing a mechanism for the enhanced temporal fidelity
      seen across the eighth nerve/cochlear nucleus synapse. Thus, depolarizing
      inhibition and threshold shifting hone the temporal response properties of this
      system so as to enhance the temporal fidelity that is essential for auditory
      perception.

PMID- 20826670
TI  - GABAergic inhibition sharpens the frequency tuning and enhances phase locking in
      chicken nucleus magnocellularis neurons.
AB  - GABAergic modulation of activity in avian cochlear nucleus neurons has been
      studied extensively in vitro. However, how this modulation actually influences
      processing in vivo is not known. We investigated responses of chicken nucleus
      magnocellularis (NM) neurons to sound while pharmacologically manipulating the
      inhibitory input from the superior olivary nucleus (SON). SON receives excitatory
      inputs from nucleus angularis (NA) and nucleus laminaris (NL), and provides
      GABAergic inputs to NM, NA, NL, and putatively to the contralateral SON. Results
      from single-unit extracellular recordings from 2 to 4 weeks posthatch chickens
      show that firing rates of auditory nerve fibers increased monotonically with
      sound intensity, while that of NM neurons saturated or even decreased at moderate
      or loud sound levels. Blocking GABAergic input with local application of TTX into
      the SON induced an increase in firing rate of ipsilateral NM, while that of the
      contralateral NM decreased at high sound levels. Moreover, local application of
      bicuculline to NM also increased the firing rate of NM neurons at high sound
      levels, reduced phase locking, and broadened the frequency-tuning properties of
      NM neurons. Following application of DNQX, clear evidence of inhibition was
      observed. Furthermore, the inhibition was tuned to a broader frequency range than
      the excitatory response areas. We conclude that GABAergic inhibition from SON has
      at least three physiological influences on the activity of NM neurons: it
      regulates the firing activity of NM units in a sound-level-dependent manner; it
      improves phase selectivity; and it sharpens frequency tuning of NM neuronal
      responses.

PMID- 20826671
TI  - Competing streams at the cocktail party: exploring the mechanisms of attention
      and temporal integration.
AB  - Processing of complex acoustic scenes depends critically on the temporal
      integration of sensory information as sounds evolve naturally over time. It has
      been previously speculated that this process is guided by both innate mechanisms
      of temporal processing in the auditory system, as well as top-down mechanisms of
      attention and possibly other schema-based processes. In an effort to unravel the
      neural underpinnings of these processes and their role in scene analysis, we
      combine magnetoencephalography (MEG) with behavioral measures in humans in the
      context of polyrhythmic tone sequences. While maintaining unchanged sensory
      input, we manipulate subjects' attention to one of two competing rhythmic streams
      in the same sequence. The results reveal that the neural representation of the
      attended rhythm is significantly enhanced in both its steady-state power and
      spatial phase coherence relative to its unattended state, closely correlating
      with its perceptual detectability for each listener. Interestingly, the data
      reveal a differential efficiency of rhythmic rates of the order of few hertz
      during the streaming process, closely following known neural and behavioral
      measures of temporal modulation sensitivity in the auditory system. These
      findings establish a direct link between known temporal modulation tuning in the
      auditory system (particularly at the level of auditory cortex) and the temporal
      integration of perceptual features in a complex acoustic scene, while mediated by
      processes of attention.

PMID- 20826672
TI  - Prion strain interactions are highly selective.
AB  - Various misfolded and aggregated neuronal proteins commonly coexist in
      neurodegenerative disease, but whether the proteins coaggregate and alter the
      disease pathogenesis is unclear. Here, we used mixtures of distinct prion
      strains, which are believed to differ in conformation, to test the hypothesis
      that two different aggregates interact and change the disease in vivo. We tracked
      two prion strains in mice histopathologically and biochemically, as well as by
      spectral analysis of plaque-bound PTAA (polythiophene acetic acid), a
      conformation-sensitive fluorescent amyloid ligand. We found that prion strains
      interacted in a highly selective and strain-specific manner, with (1) no
      interaction, (2) hybrid plaque formation, or (3) blockage of one strain by a
      second (interference). The hybrid plaques were maintained on additional passage
      in vivo and each strain seemed to maintain its original conformational
      properties, suggesting that one strain served only as a scaffold for aggregation
      of the second strain. These findings not only further our understanding of prion
      strain interactions but also directly demonstrate interactions that may occur in
      other protein aggregate mixtures.

PMID- 20826673
TI  - Chronic intermittent hypoxia induces NMDA receptor-dependent plasticity and
      suppresses nitric oxide signaling in the mouse hypothalamic paraventricular
      nucleus.
AB  - Chronic intermittent hypoxia (CIH) is a concomitant of sleep apnea that produces
      a slowly developing chemosensory-dependent blood pressure elevation ascribed in
      part to NMDA receptor-dependent plasticity and reduced nitric oxide (NO)
      signaling in the carotid body. The hypothalamic paraventricular nucleus (PVN) is
      responsive to hypoxic stress and also contains neurons that express NMDA
      receptors and neuronal nitric oxide synthase (nNOS). We tested the hypothesis
      that extended (35 d) CIH results in a decrease in the surface/synaptic
      availability of the essential NMDA NR1 subunit in nNOS-containing neurons and
      NMDA-induced NO production in the PVN of mice. As compared with controls, the 35
      d CIH-exposed mice showed a significant increase in blood pressure and an
      increased density of NR1 immunogold particles located in the cytoplasm of nNOS
      containing dendrites. Neither of these between-group differences was seen after
      14 d, even though there was already a reduction in the NR1 plasmalemmal density
      at this time point. Patch-clamp recording of PVN neurons in slices showed a
      significant reduction in NMDA currents after either 14 or 35 d exposure to CIH
      compared with sham controls. In contrast, NO production, as measured by the NO
      sensitive fluorescent dye 4-amino-5-methylamino-2',7'-difluorofluorescein, was
      suppressed only in the 35 d CIH group. We conclude that CIH produces a reduction
      in the surface/synaptic targeting of NR1 in nNOS neurons and decreases NMDA
      receptor-mediated currents in the PVN before the emergence of hypertension, the
      development of which may be enabled by suppression of NO signaling in this brain
      region.

PMID- 20826674
TI  - Kinetic properties and functional dynamics of sodium channels during repetitive
      spiking in a slow pacemaker neuron.
AB  - We examined the kinetic properties of voltage-gated Na(+) channels and their
      contribution to the repetitive spiking activity of medullary raphe neurons, which
      exhibit slow pacemaking and strong spiking adaptation. The study is based on a
      combination of whole-cell patch-clamp, modeling and real-time computation. Na(+)
      currents were recorded from neurons in brain slices obtained from male and female
      neonatal rats, using voltage-clamp protocols designed to reduce space-clamp
      artifacts and to emphasize functionally relevant kinetic features. A detailed
      kinetic model was formulated to explain the broad range of transient and
      stationary voltage-dependent properties exhibited by Na(+) currents. The model
      was tested by injecting via dynamic clamp a model-based current as a substitute
      for the native TTX-sensitive Na(+) currents, which were pharmacologically
      blocked. The model-based current reproduced well the native spike shape and
      spiking frequency. The dynamics of Na(+) channels during repetitive spiking were
      indirectly examined through this model. By comparing the spiking activities
      generated with different kinetic models in dynamic-clamp experiments, we
      determined that state-dependent slow inactivation contributes significantly to
      spiking adaptation. Through real-time manipulation of the model-based current, we
      established that suprathreshold Na(+) current mainly controls spike shape,
      whereas subthreshold Na(+) current modulates spiking frequency and contributes to
      the pacemaking mechanism. Since the model-based current was injected in the soma,
      the results also suggest that somatic Na(+) channels are sufficient to establish
      the essential spiking properties of raphe neurons in vitro.

PMID- 20826675
TI  - NMDA-mediated Ca(2+) influx drives aberrant ryanodine receptor activation in
      dendrites of young Alzheimer's disease mice.
AB  - Deficits in synaptic function, particularly through NMDA receptors (NMDARs), are
      linked to late-stage cognitive impairments in Alzheimer's disease (AD). At
      earlier disease stages, however, there is evidence for altered endoplasmic
      reticulum (ER) calcium signaling in human cases and in neurons from AD mouse
      models. Despite the fundamental importance of calcium to synaptic function,
      neither the extent of ER calcium dysregulation in dendrites nor its interaction
      with synaptic function in AD pathophysiology is known. Identifying the mechanisms
      underlying early synaptic calcium dysregulation in AD pathogenesis is likely a
      key component to understanding, and thereby preventing, the synapse loss and
      downstream cognitive impairments. Using two-photon calcium imaging, flash
      photolysis of caged glutamate, and patch-clamp electrophysiology in cortical
      brain slices, we examined interactions between synaptically and ER-evoked calcium
      release at glutamatergic synapses in young AD transgenic mice. We found increased
      ryanodine receptor-evoked calcium signals within dendritic spine heads, dendritic
      processes, and the soma of pyramidal neurons from 3xTg-AD and TAS/TPM AD mice
      relative to NonTg controls. In addition, synaptically evoked postsynaptic calcium
      responses were larger in the AD strains, as were calcium signals generated from
      NMDAR activation. However, calcium responses triggered by back-propagating action
      potentials were not different. Concurrent activation of ryanodine receptors
      (RyRs) with either synaptic or NMDAR stimulation generated a supra-additive
      calcium response in the AD strains, suggesting an aberrant calcium-induced
      calcium release (CICR) effect within spines and dendrites. We propose that
      presenilin-linked disruptions in RyR signaling and subsequent CICR via NMDAR
      mediated calcium influx alters synaptic function and serves as an early
      pathogenic factor in AD.

PMID- 20826677
TI  - Plexin a-semaphorin-1a reverse signaling regulates photoreceptor axon guidance in
      Drosophila.
AB  - While it is well established that Semaphorin family proteins function as axon
      guidance ligands in invertebrates and vertebrates, several recent studies
      indicate that the Drosophila Semaphorin-1a (Sema1a), a transmembrane Semaphorin,
      can also function as a receptor during neural development. The regulator of
      Sema1a reverse signaling, however, remains unknown. In this study, we show that
      like Sema1a, the well known Semaphorin receptor Plexin A (PlexA), is required for
      the proper guidance of photoreceptor (R cell) axons in the Drosophila visual
      system. Loss of PlexA, like loss of semala, disrupted the association of R-cell
      growth cones in the optic lobe. Conversely, overexpression of PlexA, like
      overexpression of sema1a, induced the hyperfasciculation of R-cell axons. Unlike
      Sema1a, however, the cytoplasmic domain of PlexA is dispensable. Epistasis
      analysis suggests that PlexA functions upstream of semala. And PlexA and sema1a
      interact genetically with Rho1. We propose that PlexA regulates Semala reverse
      signaling in the Drosophila visual system.

PMID- 20826676
TI  - Enhanced function of prefrontal serotonin 5-HT(2) receptors in a rat model of
      psychiatric vulnerability.
AB  - Prefrontal serotonin 5-HT(2) receptors have been linked to the pathogenesis and
      treatment of affective disorders, yet their function in psychiatric vulnerability
      is not known. Here, we examine the effects of 5-HT(2) receptors in a rat model of
      psychiatric vulnerability using electrophysiology, gene expression, and behavior.
      Following the early stress of chronic maternal separation, we found that
      serotonin has atypical 5-HT(2) receptor-mediated excitatory effects in the adult
      prefrontal cortex that were blocked by the 5-HT(2A) receptor antagonist MDL
      100907. In the absence of a serotonergic agonist, the intrinsic excitability of
      the prefrontal cortex was not enhanced relative to controls. Yet, in response to
      stimulation of 5-HT(2) receptors, adult animals with a history of early stress
      exhibit heightened prefrontal network activity in vitro, enhanced immediate early
      gene expression in vivo, and potentiated head shake behavior. These changes arise
      in the absence of any major alteration of prefrontal 5-HT(2A/C) mRNA expression
      or 5-HT(2) receptor binding. Our microarray results and quantitative PCR
      validation provide insight into the molecular changes that accompany such
      enhanced 5-HT(2) receptor function in adult animals following early stress. We
      observed persistent prefrontal transcriptome changes, with significant enrichment
      of genes involved in cellular developmental processes, regulation of signal
      transduction, and G-protein signaling. Specific genes regulated by early stress
      were validated in an independent cohort, and several altered genes were
      normalized by chronic blockade of 5-HT(2) receptors in adulthood. Together, our
      results demonstrate enhanced prefrontal 5-HT(2) receptor function and persistent
      alterations in prefrontal gene expression in a rat model of psychiatric
      vulnerability.

PMID- 20826678
TI  - Ca(2+) and Ca(2+)-activated K(+) channels that support and modulate transmitter
      release at the olivocochlear efferent-inner hair cell synapse.
AB  - In the mammalian auditory system, the synapse between efferent olivocochlear (OC)
      neurons and sensory cochlear hair cells is cholinergic, fast, and inhibitory.
      This efferent synapse is mediated by the nicotinic alpha9alpha10 receptor coupled
      to the activation of SK2 Ca(2+)-activated K(+) channels that hyperpolarize the
      cell. So far, the ion channels that support and/or modulate neurotransmitter
      release from the OC terminals remain unknown. To identify these channels, we used
      an isolated mouse cochlear preparation and monitored transmitter release from the
      efferent synaptic terminals in inner hair cells (IHCs) voltage clamped in the
      whole-cell recording configuration. Acetylcholine (ACh) release was evoked by
      electrically stimulating the efferent fibers that make axosomatic contacts with
      IHCs before the onset of hearing. Using the specific antagonists for P/Q- and N
      type voltage-gated calcium channels (VGCCs), omega-agatoxin IVA and omega
      conotoxin GVIA, respectively, we show that Ca(2+) entering through both types of
      VGCCs support the release process at this synapse. Interestingly, we found that
      Ca(2+) entering through the dihydropiridine-sensitive L-type VGCCs exerts a
      negative control on transmitter release. Moreover, using immunostaining
      techniques combined with electrophysiology and pharmacology, we show that BK
      Ca(2+)-activated K(+) channels are transiently expressed at the OC efferent
      terminals contacting IHCs and that their activity modulates the release process
      at this synapse. The effects of dihydropiridines combined with iberiotoxin, a
      specific BK channel antagonist, strongly suggest that L-type VGCCs negatively
      regulate the release of ACh by fueling BK channels that are known to curtail the
      duration of the terminal action potential in several types of neurons.

PMID- 20826679
TI  - White matter fiber degradation attenuates hemispheric asymmetry when integrating
      visuomotor information.
AB  - Degradation of white matter fibers can affect the transmission of signals in
      brain circuits that normally enable integration of highly lateralized visual and
      motor processes. Here, we used diffusion tensor imaging tractography in
      combination with functional magnetic resonance imaging to examine the specific
      contributions of interhemispheric and intrahemispheric white matter fibers to
      functional measures of hemispheric transfer and parallel information processing
      using bilateral and unilateral left and right visual field stimulation in normal
      and compromised systems. In healthy adults, a greater degree of bilateral
      processing advantage with the left (nondominant) hand correlated with higher
      integrity of callosal fibers connecting occipital cortices, whereas less
      unilateral processing advantage with the right hand correlated with higher
      integrity of left-hemispheric posterior cingulate fibers. In contrast, alcoholics
      who have compromised callosal integrity showed less bilateral processing
      advantage than controls when responding with the left hand and greater unilateral
      processing advantage when responding with the right hand. We also found degraded
      left posterior cingulate and posterior callosal fibers in chronic alcoholics,
      which is consistent with functional imaging results of less left posterior
      cingulate and extrastriate cortex activation in alcoholics than controls when
      processing bilateral compared with unilateral visual field stimulation. Together,
      our results demonstrated that interhemispheric and intrahemispheric white matter
      fiber pathways mediate visuomotor integration asymmetrically and that subtle
      white matter fiber degradation in alcoholism attenuated the normal pattern of
      hemispheric asymmetry, which may have ramifications for the efficiency of visual
      information processing and fast response execution.

PMID- 20826680
TI  - Photic entrainment of period mutant mice is predicted from their phase response
      curves.
AB  - A fundamental property of circadian clocks is that they entrain to environmental
      cues. The circadian genes, Period1 and Period2, are involved in entrainment of
      the mammalian circadian system. To investigate the roles of the Period genes in
      photic entrainment, we constructed phase response curves (PRC) to light pulses
      for C57BL/6J wild-type, Per1(-/-), Per2(-/-), and Per3(-/-) mice and tested
      whether the PRCs accurately predict entrainment to non-24 light-dark cycles (T
      cycles) and constant light (LL). The PRCs of wild-type and Per3(-/-) mice are
      similar in shape and amplitude and have relatively large delay zones and small
      advance zones, resulting in successful entrainment to 26 h T-cycles (T26), but
      not T21, with similar phase angles. Per1(-/-) mice have a high-amplitude PRC,
      resulting in entrainment to a broad range of T-cycles. Per2(-/-) mice also
      entrain to a wide range of T-cycles because the advance portion of their PRC is
      larger than wild types. Period aftereffects following entrainment to T-cycles
      were similar among all genotypes. We found that the ratio of the advance portion
      to the delay portion of the PRC accurately predicts the lengthening of the period
      of the activity rhythm in LL. Wild-type, Per1(-/-), and Per3(-/-) mice had larger
      delay zones than advance zones and lengthened (>24 h) periods in LL, whereas
      Per2(-/-) mice had delay and advance zones that were equal in size and no period
      lengthening in LL. Together, these results demonstrate that PRCs are powerful
      tools for predicting and understanding photic entrainment of circadian mutant
      mice.

PMID- 20826681
TI  - Nerve growth factor induces axonal filopodia through localized microdomains of
      phosphoinositide 3-kinase activity that drive the formation of cytoskeletal
      precursors to filopodia.
AB  - The initiation of axonal filopodia is the first step in the formation of
      collateral branches and synaptic structures. In sensory neurons, nerve growth
      factor (NGF) promotes the formation of axonal filopodia and branches. However,
      the signaling and cytoskeletal mechanisms of NGF-induced initiation of axonal
      filopodia are not clear. Axonal filopodia arise from precursor axonal
      cytoskeletal structures termed filamentous actin (F-actin) patches. Patches form
      spontaneously and are transient. Although filopodia emerge from patches, only a
      fraction of patches normally gives rise to filopodia. Using chicken sensory
      neurons and live imaging of enhanced yellow fluorescent protein (eYFP)-actin
      dynamics, we report that NGF promotes the formation of axonal filopodia by
      increasing the rate of F-actin patch formation but not the fraction of patches
      that give rise to filopodia. We also demonstrate that activation of the
      phosphatidylinositol 3-kinase (PI3K)-Akt pathway is sufficient and required for
      driving the formation of axonal F-actin patches, filopodia, and axon branches.
      Using the green fluorescent protein-plekstrin homology domain of Akt, which
      targets to PI3K-generated phosphatidylinositol-3,4,5-triphosphate (PIP(3)), we
      report localized microdomains of PIP(3) accumulation that form in synchrony with
      F-actin patches and that NGF promotes the formation of microdomains of PIP(3) and
      patches. Finally, we find that, in NGF, F-actin patches form in association with
      axonal mitochondria and oxidative phosphorylation is required for patch
      formation. This investigation demonstrates that surprisingly NGF promotes
      formation of axonal filopodia by increasing the formation of cytoskeletal
      filopodial precursors (patches) through localized microdomains of PI3K signaling
      but not the emergence of filopodia from patches.

PMID- 20826683
TI  - Tumor necrosis factor-alpha (TNF-alpha) regulates shedding of TNF-alpha receptor
      1 by the metalloprotease-disintegrin ADAM8: evidence for a protease-regulated
      feedback loop in neuroprotection.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a potent cytokine in neurodegenerative
      disorders, but its precise role in particular brain disorders is ambiguous. In
      motor neuron (MN) disease of the mouse, exemplified by the model wobbler (WR),
      TNF-alpha causes upregulation of the metalloprotease-disintegrin ADAM8 (A8) in
      affected brain regions, spinal cord, and brainstem. The functional role of A8
      during MN degeneration in the wobbler CNS was investigated by crossing WR with A8
      deficient mice: a severely aggravated neuropathology was observed for A8
      deficient WR compared with WR A8(+/-) mice, judged by drastically reduced
      survival [7 vs 81% survival at postnatal day 50 (P50)], accelerated force loss in
      the forelimbs, and terminal akinesis. In vitro protease assays using soluble A8
      indicated specific cleavage of a TNF-alpha receptor 1 (p55 TNF-R1) but not a TNF
      R2 peptide. Cleavage of TNF-R1 was confirmed in situ, because levels of soluble
      TNF-R1 were increased in spinal cords of standard WR compared with wild-type mice
      but not in A8-deficient WR mice. In isolated primary neurons and microglia, TNF
      alpha-induced TNF-R1 shedding was dependent on the A8 gene dosage. Furthermore,
      exogenous TNF-alpha showed higher toxicity for cultured neurons from A8-deficient
      than for those from wild-type mice, demonstrating that TNF-R1 shedding by A8 is
      neuroprotective. Our results indicate an essential role for ADAM8 in modulating
      TNF-alpha signaling in CNS diseases: a feedback loop integrating TNF-alpha,
      ADAM8, and TNF-R1 shedding as a plausible mechanism for TNF-alpha mediated
      neuroprotection in situ and a rationale for therapeutic intervention.

PMID- 20826682
TI  - Visual motion processing by neurons in area MT of macaque monkeys with
      experimental amblyopia.
AB  - Early experience affects the development of the visual system. Ocular
      misalignment or unilateral blur often causes amblyopia, a disorder that has
      become a standard for understanding developmental plasticity. Neurophysiological
      studies of amblyopia have focused almost entirely on the first stage of cortical
      processing in striate cortex. Here we provide the first extensive study of how
      amblyopia affects extrastriate cortex in nonhuman primates. We studied macaque
      monkeys (Macaca nemestrina) for which we have detailed psychophysical data,
      directly comparing physiological findings to perceptual capabilities. Because
      these subjects showed deficits in motion discrimination, we focused on area
      MT/V5, which plays a central role in motion processing. Most neurons in normal MT
      respond equally to visual stimuli presented through either eye; most recorded in
      amblyopes strongly preferred stimulation of the nonamblyopic (fellow) eye. The
      pooled responses of neurons driven by the amblyopic eye showed reduced
      sensitivity to coherent motion and preferred higher speeds, in agreement with
      behavioral measurements. MT neurons were more limited in their capacity to
      integrate motion information over time than expected from behavioral performance;
      neurons driven by the amblyopic eye had even shorter integration times than those
      driven by the fellow eye. We conclude that some, but not all, of the motion
      sensitivity deficits associated with amblyopia can be explained by abnormal
      development of MT.

PMID- 20826684
TI  - A comparison of three strategies for scale construction to predict a specific
      behavioral outcome.
AB  - Using 65 items from a mental health screening questionnaire, the History Opinion
      Inventory-Revised (HOI-R), the present study compared three strategies of scale
      construction-(1) internal (based on factor analysis), (2) external (based on
      empirical performance) and (3) intuitive (based on clinicians' opinion)-to
      predict whether 203,595 U.S. Air Force trainees would be discharged early for
      mental health or behavior-related reasons within a 4-year follow-up period. The
      external strategy significantly outperformed the internal strategy, which in turn
      outperformed the intuitive strategy. For all strategies, predictive accuracy was
      consistently higher when items and scales were scored using empirically derived
      weights rather than unit weights. These findings suggest that the external
      strategy of scale construction provides the highest accuracy when sample sizes
      are large and the aim is to predict a specific behavioral event. However, the
      internal strategy also yields valid results and can be a reasonable choice when
      outcome data are unavailable.

PMID- 20826685
TI  - Augmenting the core battery with supplementary subtests: Wechsler adult
      intelligence scale--IV measurement invariance across the United States and
      Canada.
AB  - Examination of measurement invariance provides a powerful method to evaluate the
      hypothesis that the same set of psychological constructs underlies a set of test
      scores in different populations. If measurement invariance is observed, then the
      same psychological meaning can be ascribed to scores in both populations. In this
      study, the measurement model including core and supplementary subtests of the
      Wechsler Adult Intelligence Scale-Fourth edition (WAIS-IV) were compared across
      the U.S. and Canadian standardization samples. Populations were compared on the
      15 subtest version of the test in people aged 70 and younger and on the 12
      subtest version in people aged 70 or older. Results indicated that a slightly
      modified version of the four-factor model reported in the WAIS-IV technical
      manual provided the best fit in both populations and in both age groups. The null
      hypothesis of measurement invariance across populations was not rejected, and the
      results provide direct evidence for the generalizability of convergent and
      discriminant validity studies with the WAIS-IV across populations. Small to
      medium differences in latent means favoring Canadians highlight the value of
      local norms.

PMID- 20826686
TI  - Fluidity of HIV-1-specific T-cell responses during acute and early subtype C HIV
      1 infection and associations with early disease progression.
AB  - Deciphering immune events during early stages of human immunodeficiency virus
      type 1 (HIV-1) infection is critical for understanding the course of disease. We
      characterized the hierarchy of HIV-1-specific T-cell gamma interferon (IFN-gamma)
      enzyme-linked immunospot (ELISPOT) assay responses during acute subtype C
      infection in 53 individuals and associated temporal patterns of responses with
      disease progression in the first 12 months. There was a diverse pattern of T-cell
      recognition across the proteome, with the recognition of Nef being immunodominant
      as early as 3 weeks postinfection. Over the first 6 months, we found that there
      was a 23% chance of an increased response to Nef for every week postinfection (P
      = 0.0024), followed by a nonsignificant increase to Pol (4.6%) and Gag (3.2%).
      Responses to Env and regulatory proteins appeared to remain stable. Three
      temporal patterns of HIV-specific T-cell responses could be distinguished:
      persistent, lost, or new. The proportion of persistent T-cell responses was
      significantly lower (P = 0.0037) in individuals defined as rapid progressors than
      in those progressing slowly and who controlled viremia. Almost 90% of lost T-cell
      responses were coincidental with autologous viral epitope escape. Regression
      analysis between the time to fixed viral escape and lost T-cell responses (r =
      0.61; P = 0.019) showed a mean delay of 14 weeks after viral escape.
      Collectively, T-cell epitope recognition is not a static event, and temporal
      patterns of IFN-gamma-based responses exist. This is due partly to viral sequence
      variation but also to the recognition of invariant viral epitopes that leads to
      waves of persistent T-cell immunity, which appears to associate with slower
      disease progression in the first year of infection.

PMID- 20826687
TI  - Pseudorevertants of a Semliki forest virus fusion-blocking mutation reveal a
      critical interchain interaction in the core trimer.
AB  - Semliki Forest virus (SFV) is an enveloped alphavirus that infects cells by a low
      pH-triggered membrane fusion reaction mediated by the viral E1 protein. E1
      inserts into target membranes and refolds to a hairpin-like homotrimer containing
      a central core trimer and an outer layer composed of domain III and the
      juxtamembrane stem region. The key residues involved in mediating E1
      trimerization are not well understood. We recently showed that aspartate 188 in
      the interface of the core trimer plays a critical role. Substitution with lysine
      (D188K) blocks formation of the core trimer and E1 trimerization and strongly
      inhibits virus fusion and infection. Here, we have isolated and characterized
      revertants that rescued the fusion and growth defects of D188K. These revertants
      included pseudorevertants containing acidic or polar neutral residues at E1
      position 188 and a second-site revertant containing an E1 K176T mutation.
      Computational analysis using multiconformation continuum electrostatics revealed
      an important interaction bridging D188 of one chain with K176 of the adjacent
      chain in the core trimer. E1 K176 is completely conserved among the alphaviruses,
      and mutations of K176 to threonine (K176T) or isoleucine (K176I) produced similar
      fusion phenotypes as D188 mutants. Together, our data support a model in which a
      ring of three salt bridges formed by D188 and K176 stabilize the core trimer, a
      key intermediate of the alphavirus fusion protein.

PMID- 20826689
TI  - Infectivity of hepatitis C virus is influenced by association with apolipoprotein
      E isoforms.
AB  - Hepatitis C virus (HCV) is a causative agent of chronic hepatitis, liver
      cirrhosis, and hepatocellular carcinoma. HCV in circulating blood associates with
      lipoproteins such as very low density lipoprotein (VLDL) and low-density
      lipoprotein (LDL). Although these associations suggest that lipoproteins are
      important for HCV infectivity, the roles of lipoproteins in HCV production and
      infectivity are not fully understood. To clarify the roles of lipoprotein in the
      HCV life cycle, we analyzed the effect of apolipoprotein E (ApoE), a component of
      lipoprotein, on virus production and infectivity. The production of infectious
      HCV was significantly reduced by the knockdown of ApoE. When an ApoE mutant that
      fails to be secreted into the culture medium was used, the amount of infectious
      HCV in the culture medium was dramatically reduced; the infectious HCV
      accumulated inside these cells, suggesting that infectious HCV must associate
      with ApoE prior to virus release. We performed rescue experiments in which ApoE
      isoforms were ectopically expressed in cells depleted of endogenous ApoE. The
      ectopic expression of the ApoE2 isoform, which has low affinity for the LDL
      receptor (LDLR), resulted in poor recovery of infectious HCV, whereas the
      expression of other isoforms, ApoE3 and ApoE4, rescued the production of
      infectious virus, raising it to an almost normal level. Furthermore, we found
      that the infectivity of HCV required both the LDLR and scavenger receptor class
      B, member I (SR-BI), ligands for ApoE. These findings indicate that ApoE is an
      essential apolipoprotein for HCV infectivity.

PMID- 20826688
TI  - Altered receptor specificity and cell tropism of D222G hemagglutinin mutants
      isolated from fatal cases of pandemic A(H1N1) 2009 influenza virus.
AB  - Mutations in the receptor-binding site of the hemagglutinin of pandemic influenza
      A(H1N1) 2009 viruses have been detected sporadically. An Asp222Gly (D222G)
      substitution has been associated with severe or fatal disease. Here we show that
      222G variants infected a higher proportion of ciliated cells in cultures of human
      airway epithelium than did viruses with 222D or 222E, which targeted mainly
      nonciliated cells. Carbohydrate microarray analyses showed that 222G variants
      bind a broader range of alpha2-3-linked sialyl receptor sequences of a type
      expressed on ciliated bronchial epithelial cells and on epithelia within the
      lung. These features of 222G mutants may contribute to exacerbation of disease.

PMID- 20826690
TI  - Rhesus rhadinovirus infection of rhesus fibroblasts occurs through clathrin
      mediated endocytosis.
AB  - Rhesus rhadinovirus (RRV) is a gammaherpesvirus closely related to Kaposi's
      sarcoma-associated herpesvirus (KSHV), an oncogenic virus linked to the
      development of Kaposi's sarcoma and several other lymphoproliferative diseases,
      including primary effusion lymphoma and multicentric Castleman's disease. RRV
      naturally infects rhesus macaques and induces lymphoproliferative diseases under
      experimental conditions, making it an excellent model for the study of KSHV.
      Unlike KSHV, which grows poorly in cell culture, RRV replicates efficiently in
      rhesus fibroblasts (RFs). In this study, we have characterized the entry pathway
      of RRV in RFs. Using a luciferase-expressing recombinant RRV (RRV-luciferase), we
      show that the infectivity of RRV is reduced by inhibitors of endosomal
      acidification. RRV infectivity is also reduced by inhibitors of clathrin-mediated
      but not caveola-mediated endocytosis, indicating that RRV enters into RFs via
      clathrin-mediated endocytosis. Using a red fluorescent protein (RFP)-expressing
      recombinant RRV (RRV-RFP), we show that RRV particles are colocalized with
      markers of endocytosis (early endosome antigen 1) and clathrin-mediated
      endocytosis (clathrin heavy chain) during entry into RFs. RRV particles are also
      colocalized with transferrin, which enters cells by clathrin-mediated
      endocytosis, but not with cholera toxin B, which enters cells by caveola-mediated
      endocytosis. Inhibition of clathrin-mediated endocytosis with a dominant-negative
      construct of EPS15, an essential component of clathrin-coated pits, blocked the
      entry of RRV into RFs. Together, these results indicate that RRV entry into RFs
      is mediated by clathrin-mediated endocytosis.

PMID- 20826691
TI  - A 27-amino-acid deletion in the neuraminidase stalk supports replication of an
      avian H2N2 influenza A virus in the respiratory tract of chickens.
AB  - The events and mechanisms that lead to interspecies transmission of, and host
      adaptation to, influenza A virus are unknown; however, both surface and internal
      proteins have been implicated. Our previous report highlighted the role that
      Japanese quail play as an intermediate host, expanding the host range of a
      mallard H2N2 virus, A/mallard/Potsdam/178-4/83 (H2N2), through viral adaptation.
      This quail-adapted virus supported transmission in quail and increased its host
      range to replicate and be transmitted efficiently in chickens. Here we report
      that of the six amino acid changes in the quail-adapted virus, a single change in
      the hemagglutinin (HA) was crucial for transmission in quail, while the changes
      in the polymerase genes favored replication at lower temperatures than those for
      the wild-type mallard virus. Reverse genetic analysis indicated that all adaptive
      mutations were necessary for transmission in chickens, further implicating quail
      in extending this virus to terrestrial poultry. Adaptation of the quail-adapted
      virus in chickens resulted in the alteration of viral tropism from intestinal
      shedding to shedding and transmission via the respiratory tract. Sequence
      analysis indicated that this chicken-adapted virus maintained all quail-adaptive
      mutations, as well as an additional change in the HA and, most notably, a 27
      amino-acid deletion in the stalk region of neuraminidase (NA), a genotypic marker
      of influenza virus adaptation to chickens. This stalk deletion was shown to be
      responsible for the change in virus tropism from the intestine to the respiratory
      tract.

PMID- 20826692
TI  - Generation of replication-competent recombinant influenza A viruses carrying a
      reporter gene harbored in the neuraminidase segment.
AB  - Replication-competent influenza viruses carrying reporter genes are of great use
      for basic research, screening of antiviral drugs, and neutralizing of antibodies.
      In this study, two recombinant influenza A viruses with a neuraminidase (NA)
      segment harboring enhanced green fluorescent protein (EGFP) in the background of
      A/PR/8/34 (PR8) were generated. The viral RNA (vRNA)-specific packaging signals
      for NA were largely retained for efficient packaging. An "autocleave" 2A peptide
      sequence, which was inserted at the N terminus or the COOH terminus of NA to link
      with EGFP, enabled NA and EGFP to be expressed monocistronically. Further
      analysis demonstrated that both viruses, named rPR8-EGFP+NA and rPR8-NA+EGPF,
      although with some characteristic differences in growth and EGFP expression,
      could replicate in noncomplementary cells and propagate to large quantities while
      maintaining genome stability after multiple passages in embryonated eggs. These
      replication-competent influenza viruses carrying reporter genes are a great
      addition to the tool set for developing antiviral therapeutics and vaccines and
      for in vivo studies of viral dissemination and pathogenicity.

PMID- 20826693
TI  - Herpes simplex virus glycoprotein D interferes with binding of herpesvirus entry
      mediator to its ligands through downregulation and direct competition.
AB  - To initiate membrane fusion and virus entry, herpes simplex virus (HSV) gD binds
      to a cellular receptor such as herpesvirus entry mediator (HVEM). HVEM is a tumor
      necrosis factor (TNF) receptor family member with four natural ligands that
      either stimulate (LIGHT and LTalpha) or inhibit (BTLA and CD160) T cell function.
      We hypothesized that the interaction of gD with HVEM affects the binding of
      natural ligands, thereby modulating the immune response during infection. Here,
      we investigated the effect that gD has on the interaction of HVEM with its
      natural ligands. First, HSV gD on virions or cells downregulates HVEM from the
      cell surface. Similarly, trans-interaction with BTLA or LIGHT also downregulates
      HVEM from the cell surface, suggesting that HSV may subvert a natural mechanism
      for regulating HVEM activity. Second, we showed that wild-type gD had the lowest
      affinity for HVEM compared with the four natural ligands. Moreover, gD directly
      competed for binding to HVEM with BTLA but not LTalpha or LIGHT, indicating the
      possibility that gD selectively controls HVEM signals. On the other hand, natural
      ligands influence the use of HVEM by HSV. For instance, soluble BTLA, LTalpha,
      and LIGHT inhibited the binding of wild-type gD to HVEM, and soluble BTLA and
      LTalpha blocked HSV infection of HVEM-expressing cells. Thus, gD is at the center
      of the interplay between HVEM and its ligands. It can interfere with HVEM
      function in two ways, by competing with the natural ligands and by downregulating
      HVEM from the cell surface.

PMID- 20826694
TI  - SUMOylation promotes PML degradation during encephalomyocarditis virus infection.
AB  - The promyelocytic leukemia (PML) protein is expressed in the diffuse nuclear
      fraction of the nucleoplasm and in matrix-associated structures, known as nuclear
      bodies (NBs). PML NB formation requires the covalent modification of PML to SUMO.
      The noncovalent interactions of SUMO with PML based on the identification of a
      SUMO-interacting motif within PML seem to be required for further recruitment
      within PML NBs of SUMOylated proteins. RNA viruses whose replication takes place
      in the cytoplasm and is inhibited by PML have developed various strategies to
      counteract the antiviral defense mediated by PML NBs. We show here that primary
      fibroblasts derived from PML knockout mice are more sensitive to infection with
      encephalomyocarditis virus (EMCV), suggesting that the absence of PML results in
      an increase in EMCV replication. Also, we found that EMCV induces a decrease in
      PML protein levels both in interferon-treated cells and in PMLIII-expressing
      cells. Reduction of PML was carried out by the EMCV 3C protease. Indeed, at early
      times postinfection, EMCV induced PML transfer from the nucleoplasm to the
      nuclear matrix and PML conjugation to SUMO-1, SUMO-2, and SUMO-3, leading to an
      increase in PML body size where the viral protease 3C and the proteasome
      component were found colocalizing with PML within the NBs. This process was
      followed by PML degradation occurring in a proteasome- and SUMO-dependent manner
      and did not involve the SUMO-interacting motif of PML. Together, these findings
      reveal a new mechanism evolved by EMCV to antagonize the PML pathway in the
      interferon-induced antiviral defense.

PMID- 20826695
TI  - Impact of ETIF deletion on safety and immunogenicity of equine herpesvirus type 1
      vectored vaccines.
AB  - Heterologous gene transfer by viral vector systems is often limited by factors
      such as preexisting immunity, toxicity, low packaging capacity, or weak
      immunogenic potential. A novel viral vector system derived from equine
      herpesvirus type 1 (EHV-1) not only overcomes some of these obstacles but also
      promotes the robust expression of a delivered transgene and the induction of
      antigen-specific immune responses. Regarding an enhanced safety profile, we
      assessed the impact of the gene encoding the sole essential tegument protein,
      ETIF, on the replication and immunogenicity of recombinant EHVs. The deletion of
      ETIF severely attenuates replication in permissive RK13 cells and a human lung
      epithelial cell line but without influencing transgene expression. Whereas the
      intranasal administration of a recombinant luciferase EHV in BALB/c mice resulted
      in transgene expression in nasal cavities and lungs for 5 to 6 days, the ETIF
      deletion limited expression to 2 days and resulted in 30-fold-less luminescence.
      Attenuated replication was accompanied by a decreased capacity to induce CD8(+) T
      cells against a delivered HIV Gag transgene in BALB/c mice following repeated
      intranasal application. However, a single subcutaneous immunization with a gag
      DNA vaccine primed specific T cells for substantial expansion by two subsequent
      intranasal booster immunizations with either the gag recombinant ETIF mutant or
      the parental virus. In addition to inducing Gag-specific serum antibodies, this
      prime-boost strategy clearly outperformed three sequential immunizations with the
      parental or EHV-DeltaETIF virus or repeated DNA vaccination by inducing
      substantial specific secretory IgA (sIgA) titers.

PMID- 20826696
TI  - Functional Sindbis virus replicative complexes are formed at the plasma membrane.
AB  - Formation of virus-specific replicative complexes (RCs) in infected cells is one
      of the most intriguing and important processes that determine virus replication
      and ultimately their pathogenesis on the molecular and cellular levels.
      Alphavirus replication was known to lead to formation of so-called type 1
      cytopathic vacuoles (CPV1s), whose distinguishing feature is the presence of
      numerous membrane invaginations (spherules) and accumulation of viral
      nonstructural proteins (nsPs) at the cytoplasmic necks of these spherules. These
      CPV1s, modified endosomes and lysosomes, were proposed as the sites of viral RNA
      synthesis. However, our recent studies have demonstrated that Sindbis virus
      (SINV)-specific, double-stranded RNA (dsRNA)- and nonstructural protein (nsP)
      containing RCs are initially formed at the plasma membrane. In this new study, we
      present extensive evidence that (i) in cells of vertebrate origin, at early times
      postinfection, viral nsPs colocalize with spherules at the plasma membrane; (ii)
      viral dsRNA intermediates are packed into membrane spherules and are located in
      their cavities on the external surface of the plasma membrane; (iii) formation of
      the membrane spherules is induced by the partially processed nonstructural
      polyprotein P123 and nsP4, but synthesis of dsRNA is an essential prerequisite of
      their formation; (iv) plasma membrane-associated dsRNA and protein structures are
      the active sites of single-stranded RNA (ssRNA) synthesis; (v) at late times
      postinfection, only a small fraction of SINV nsP-containing complexes are
      relocalized into the cytoplasm on the endosome membrane. (vi) pharmacological
      drugs inhibiting different endocytotic pathways have either only minor or no
      negative effects on SINV RNA replication; and (vii) in mosquito cells, at any
      times postinfection, dsRNA/nsP complexes and spherules are associated with both
      endosomal/lysosomal and plasma membranes, suggesting that mechanisms of RC
      formation may differ in cells of insect and vertebrate origins.

PMID- 20826697
TI  - The globoside receptor triggers structural changes in the B19 virus capsid that
      facilitate virus internalization.
AB  - Globoside (Gb4Cer), Ku80 autoantigen, and alpha5beta1 integrin have been
      identified as cell receptors/coreceptors for human parvovirus B19 (B19V), but
      their role and mechanism of interaction with the virus are largely unknown. In
      UT7/Epo cells, expression of Gb4Cer and CD49e (integrin alpha-5) was high, but
      expression of Ku80 was insignificant. B19V colocalized with Gb4Cer and, to a
      lesser extent, with CD49e. However, only anti-Gb4Cer antibodies could disturb
      virus attachment. Only a small proportion of cell-bound viruses were
      internalized, while the majority became detached from the receptor. When added to
      uninfected cells, the receptor-detached virus showed superior cell binding
      capacity and infectivity. Attachment of B19V to cells triggered conformational
      changes in the capsid leading to the accessibility of the N terminus of VP1
      (VP1u) to antibodies, which was maintained in the receptor-detached virus. VP1u
      became similarly accessible to antibodies following incubation of B19V particles
      with increasing concentrations of purified Gb4Cer. The receptor-mediated exposure
      of VP1u is critical for virus internalization, since capsids lacking VP1 could
      bind to cells but were not internalized. Moreover, an antibody against the N
      terminus of VP1u disturbed virus internalization, but only when present during
      and not after virus attachment, indicating the involvement of this region in
      binding events required for internalization. These results suggest that Gb4Cer is
      not only the primary receptor for B19V attachment but also the mediator of capsid
      rearrangements required for subsequent interactions leading to virus
      internalization. The capacity of the virus to detach and reattach again would
      enhance the probability of productive infections.

PMID- 20826698
TI  - Quantifying antigenic relationships among the lyssaviruses.
AB  - All lyssaviruses cause fatal encephalitis in mammals. There is sufficient
      antigenic variation within the genus to cause variable vaccine efficacy, but this
      variation is difficult to characterize quantitatively: sequence analysis cannot
      yet provide detailed antigenic information, and antigenic neutralization data
      have been refractory to high-resolution robust interpretation. Here, we address
      these issues by using state-of-the-art antigenic analyses to generate a high
      resolution antigenic map of a global panel of 25 lyssaviruses. We compared the
      calculated antigenic distances with viral glycoprotein ectodomain sequence data.
      Although 67% of antigenic variation was predictable from the glycoprotein amino
      acid sequence, there are in some cases substantial differences between genetic
      and antigenic distances, thus highlighting the risk of inferring antigenic
      relationships solely from sequence data at this time. These differences included
      epidemiologically important antigenic differences between vaccine strains and
      wild-type rabies viruses. Further, we quantitatively assessed the antigenic
      relationships measured by using rabbit, mouse, and human sera, validating the use
      of nonhuman experimental animals as a model for determining antigenic variation
      in humans. The use of passive immune globulin is a crucial component of rabies
      postexposure prophylaxis, and here we also show that it is possible to predict
      the reactivity of immune globulin against divergent lyssaviruses.

PMID- 20826699
TI  - Distinct functions of maternal and somatic Pat1 protein paralogs.
AB  - We previously identified Xenopus Pat1a (P100) as a member of the maternal CPEB
      RNP complex, whose components resemble those of P-(rocessing) bodies, and which
      is implicated in translational control in Xenopus oocytes. Database searches have
      identified Pat1a proteins in other vertebrates, as well as paralogous Pat1b
      proteins. Here we characterize Pat1 proteins, which have no readily discernable
      sequence features, in Xenopus oocytes, eggs, and early embryos and in human
      tissue culture cells. xPat1a and 1b have essentially mutually exclusive
      expression patterns in oogenesis and embryogenesis. xPat1a is degraded during
      meiotic maturation, via PEST-like regions, while xPat1b mRNA is translationally
      activated at GVBD by cytoplasmic polyadenylation. Pat1 proteins bind RNA in
      vitro, via a central domain, with a preference for G-rich sequences, including
      the NRAS 5' UTR G-quadruplex-forming sequence. When tethered to reporter mRNA,
      both Pat proteins repress translation in oocytes. Indeed, both epitope-tagged
      proteins interact with the same components of the CPEB RNP complex, including
      CPEB, Xp54, eIF4E1b, Rap55B, and ePAB. However, examining endogenous protein
      interactions, we find that in oocytes only xPat1a is a bona fide component of the
      CPEB RNP, and that xPat1b resides in a separate large complex. In tissue culture
      cells, hPat1b localizes to P-bodies, while mPat1a-GFP is either found weakly in P
      bodies or disperses P-bodies in a dominant-negative fashion. Altogether we
      conclude that Pat1a and Pat1b proteins have distinct functions, mediated in
      separate complexes. Pat1a is a translational repressor in oocytes in a CPEB
      containing complex, and Pat1b is a component of P-bodies in somatic cells.

PMID- 20826700
TI  - Metal binding and substrate positioning by evolutionarily invariant U6 sequences
      in catalytically active protein-free snRNAs.
AB  - We have previously shown that a base-paired complex formed by two of the
      spliceosomal RNA components, U6 and U2 small nuclear RNAs (snRNAs), can catalyze
      a two-step splicing reaction that depended on an evolutionarily invariant region
      in U6, the ACAGAGA box. Here we further analyze this RNA-catalyzed reaction and
      show that while the 5' and 3' splice site substrates are juxtaposed and
      positioned near the ACAGAGA sequence in U6, the role of the snRNAs in the
      reaction is beyond mere juxtaposition of the substrates and likely involves the
      formation of a sophisticated active site. Interestingly, the snRNA-catalyzed
      reaction is metal dependent, as is the case with other known splicing RNA
      enzymes, and terbium(III) cleavage reactions indicate metal binding by the U6/U2
      complex within the evolutionarily conserved regions of U6. The above results,
      combined with the structural similarities between U6 and catalytically critical
      domains in group II self-splicing introns, suggest that the base-paired complex
      of U6 and U2 snRNAs is a vestigial ribozyme and a likely descendant of a group II
      like self-splicing intron.

PMID- 20826701
TI  - MORPHEUS' MOLECULE1 is required to prevent aberrant RNA transcriptional read
      through in Arabidopsis.
AB  - Several pathways function to remove aberrant mRNA in eukaryotic cells; however,
      the exact mechanisms underlying the restriction of aberrant mRNA transcription
      are poorly understood. In this study, we found that MORPHEUS' MOLECULE1 (MOM1) is
      a key component of this regulatory machinery. The Arabidopsis (Arabidopsis
      thaliana) mom1-44 mutation was identified by luciferase imaging in transgenic
      plants harboring a cauliflower mosaic virus 35S promoter-LUCIFERASE transgene
      lacking the 3'-untranslated region. In the mom1-44 mutant, transcriptional read
      though occurred in genes with an aberrant RNA structure. Analysis of an RNA
      dependent RNA polymerase2 mom1 double mutant revealed that the RNA-directed DNA
      methylation pathway is not involved in this regulatory process. Moreover, the
      prevention of aberrant mRNA transcriptional read-through by MOM1 is gene locus
      and transgene copy number independent.

PMID- 20826703
TI  - Relationships between growth, growth response to nutrient supply, and ion content
      using a recombinant inbred line population in Arabidopsis.
AB  - Growth is an integrative trait that responds to environmental factors and is
      crucial for plant fitness. A major environmental factor influencing plant growth
      is nutrient supply. In order to explore this relationship further, we quantified
      growth-related traits, ion content, and other biochemical traits (protein,
      hexose, and chlorophyll contents) of a recombinant inbred line population of
      Arabidopsis (Arabidopsis thaliana) grown on different levels of potassium and
      phosphate. Performing an all subsets multiple regression analyses revealed a link
      between growth-related traits and mineral nutrient content. Based on our results,
      up to 85% of growth variation can be explained by variation in ion content,
      highlighting the importance of ionomics for a broader understanding of plant
      growth. In addition, quantitative trait loci (QTLs) were detected for growth
      related traits, ion content, further biochemical traits, and their responses to
      reduced supplies of potassium or phosphate. Colocalization of these QTLs is
      explored, and candidate genes are discussed. A QTL for rosette weight response to
      reduced potassium supply was identified on the bottom of chromosome 5, and its
      effects were validated using selected near isogenic lines. These lines retained
      over 20% more rosette weight in reduced potassium supply, accompanied by an
      increase in potassium content in their leaves.

PMID- 20826702
TI  - Identification of putative stage-specific grapevine berry biomarkers and omics
      data integration into networks.
AB  - The analysis of grapevine (Vitis vinifera) berries at the transcriptomic,
      proteomic, and metabolomic levels can provide great insight into the molecular
      events underlying berry development and postharvest drying (withering). However,
      the large and very different data sets produced by such investigations are
      difficult to integrate. Here, we report the identification of putative stage
      specific biomarkers for berry development and withering and, to our knowledge,
      the first integrated systems-level study of these processes. Transcriptomic,
      proteomic, and metabolomic data were integrated using two different strategies,
      one hypothesis free and the other hypothesis driven. A multistep hypothesis-free
      approach was applied to data from four developmental stages and three withering
      intervals, with integration achieved using a hierarchical clustering strategy
      based on the multivariate bidirectional orthogonal projections to latent
      structures technique. This identified stage-specific functional networks of
      linked transcripts, proteins, and metabolites, providing important insights into
      the key molecular processes that determine the quality characteristics of wine.
      The hypothesis-driven approach was used to integrate data from three withering
      intervals, starting with subdata sets of transcripts, proteins, and metabolites.
      We identified transcripts and proteins that were modulated during withering as
      well as specific classes of metabolites that accumulated at the same time and
      used these to select subdata sets of variables. The multivariate bidirectional
      orthogonal projections to latent structures technique was then used to integrate
      the subdata sets, identifying variables representing selected molecular processes
      that take place specifically during berry withering. The impact of this holistic
      approach on our knowledge of grapevine berry development and withering is
      discussed.

PMID- 20826704
TI  - Auxin carriers localization drives auxin accumulation in plant cells infected by
      Frankia in Casuarina glauca actinorhizal nodules.
AB  - Actinorhizal symbioses are mutualistic interactions between plants and the soil
      bacteria Frankia that lead to the formation of nitrogen-fixing root nodules.
      Little is known about the signaling mechanisms controlling the different steps of
      the establishment of the symbiosis. The plant hormone auxin has been suggested to
      play a role. Here we report that auxin accumulates within Frankia-infected cells
      in actinorhizal nodules of Casuarina glauca. Using a combination of computational
      modeling and experimental approaches, we establish that this localized auxin
      accumulation is driven by the cell-specific expression of auxin transporters and
      by Frankia auxin biosynthesis in planta. Our results indicate that the plant
      actively restricts auxin accumulation to Frankia-infected cells during the
      symbiotic interaction.

PMID- 20826705
TI  - Adaptive thermogenesis and thermal conductance in wild-type and UCP1-KO mice.
AB  - We compared maximal cold-induced heat production (HPmax) and cold limits between
      warm (WA; 27 degrees C), moderate cold (MCA; 18 degrees C), or cold acclimated
      (CA; 5 degrees C) wild-type and uncoupling-protein 1 knockout (UCP1-KO) mice. In
      wild-type mice, HPmax was successively increased after MCA and CA, and the cold
      limit was lowered to -8.3 degrees C and -18.0 degrees C, respectively. UCP1-KO
      mice also increased HPmax in response to MCA and CA, although to a lesser extent.
      Direct comparison revealed a maximal cold-induced recruitment of heat production
      by +473 mW and +227 mW in wild-type and UCP1-KO mice, respectively. The increase
      in cold tolerance of UCP1-KO mice from -0.9 degrees C in MCA to -10.1 degrees C
      in CA could not be directly related to changes in HPmax, indicating that UCP1-KO
      mice used the dissipated heat more efficiently than wild-type mice. As judged
      from respiratory quotients, acutely cold-challenged UCP1-KO mice showed a delayed
      transition toward lipid oxidation, and 5-h cold exposure revealed diminished
      physical activity and less variability in the control of metabolic rate. We
      conclude that BAT is required for maximal adaptive thermogenesis but also allows
      metabolic flexibility and a rapid switch toward sustained lipid-fuelled
      thermogenesis as an acute response to cold. In both CA groups, expression of
      contractile proteins (myosin heavy-chain isoforms) showed minor training effects
      in skeletal muscles, while cardiac muscle of UCP1-KO mice had novel expression of
      beta cardiac isoform. Neither respiration nor basal proton conductance of
      skeletal muscle mitochondria were different between genotypes. In subcutaneous
      white adipose tissue of UCP1-KO mice, cold exposure increased cytochrome-c
      oxidase activity and expression of the cell death-inducing DFFA-like effector A
      by 3.6-fold and 15-fold, respectively, indicating the recruitment of mitochondria
      rich brown adipocyte-like cells. Absence of functional BAT leads to remodeling of
      white adipose tissue, which may significantly contribute to adaptive
      thermogenesis during cold acclimation.

PMID- 20826706
TI  - Ventilatory restraint of sympathetic activity during chemoreflex stress.
AB  - The within-breath modulation of muscle sympathetic nerve activity (MSNA) is well
      established, with greater activity occurring during expiration and less during
      inspiration. Whether ventilation per se affects the longer-term (i.e., minute-to
      minute) regulation of MSNA has not been determined. We sought to define the
      specific role of ventilation in regulating sympathetic activation during
      chemoreflex activation, where both ventilation and MSNA are increased. Ten young
      healthy subjects performed both asphyxic rebreathing and repeated, rebreathing
      apneas to cause the same magnitude of chemoreflex stress in the presence or
      absence of ventilation. Both protocols caused increases in sympathetic burst
      frequency, burst amplitude, and burst incidence. However, burst frequency was
      increased more during repeated apneas (12 +/- 6 to 25 +/- 7 bursts/min) compared
      with rebreathing (12 +/- 5 to 17 +/- 7 bursts/min; P < 0.001) due to a greater
      burst incidence during apneas (36 +/- 11 bursts/100 heart beats) vs. rebreathing
      (26 +/- 8 bursts/100 heart beats, P < 0.001). The sympathetic gain to chemoreflex
      stress was also larger during repeated apneas (2.29 +/- 1.29 au/% desaturation)
      compared with rebreathing (1.44 +/- 0.53 au/% desaturation, P < 0.05). The
      augmented sympathetic response during apneas was associated with a larger pressor
      response and total peripheral resistance compared with rebreathing. These data
      demonstrate that ventilation per se restrains sympathetic activation during
      chemoreflex activation. Further, the augmented sympathetic response during apneas
      was associated with greater cardiovascular stress and may be relevant to the
      cardiovascular pathology associated with sleep-disordered breathing.

PMID- 20826707
TI  - Carotid baroreflex control of arterial blood pressure at rest and during dynamic
      exercise in aging humans.
AB  - The arterial baroreflex is fundamental for evoking and maintaining appropriate
      cardiovascular adjustments to exercise. We sought to investigate how aging
      influences carotid baroreflex regulation of blood pressure (BP) during dynamic
      exercise. BP and heart rate (HR) were continuously recorded at rest and during
      leg cycling performed at 50% HR reserve in 15 young (22 +/- 1 yr) and 11 older
      (61 +/- 2 yr) healthy subjects. Five-second pulses of neck pressure and neck
      suction from +40 to -80 Torr were applied to determine the full carotid
      baroreflex stimulus response curve and examine baroreflex resetting during
      exercise. Although the maximal gain of the modeled stimulus response curve was
      similar in both groups at rest and during exercise, in older subjects the
      operating point (OP) was located further away from the centering point (CP) and
      toward the reflex threshold, both at rest (OP minus CP; -10 +/- 3 older vs. 0 +/-
      2 young mmHg, P < 0.05) and during exercise (OP minus CP; -10 +/- 2 older vs. 1
      +/- 3 young mmHg, P < 0.05). In agreement, older subjects demonstrated a reduced
      BP response to neck pressure (simulated carotid hypotension) and a greater BP
      response to neck suction (simulated carotid hypertension). In addition, the
      magnitude of the upward and rightward resetting of the carotid baroreflex-BP
      stimulus response curve with exercise was ~40% greater in older individuals.
      These data indicate that despite a maintained maximal gain, the ability of the
      carotid baroreflex to defend against a hypotensive challenge is reduced, whereas
      responses to hypertensive stimuli are greater with advanced age, both at rest and
      during exercise.

PMID- 20826708
TI  - Health-related quality of life in caregivers of individuals with dementia from
      Colombia.
AB  - The purpose of this study was to compare the health-related quality of life
      (HRQoL) of 99 caregivers of individuals with dementia and 95 healthy individuals
      from the general population in Colombia. The 36-item short-form (SF-36), a self
      report measure composed of 8 component areas (physical function, role-physical,
      bodily pain, general health, energy/vitality, social function, role-emotional,
      and mental health), was used to measure HRQoL. Results indicated that the healthy
      control group had a higher level of education, socioeconomic status (SES), and
      number of male participants. After adjusting for education, SES, and gender, the
      caregivers of individuals with dementia scored significantly lower on all of the
      SF-36 subscales than the healthy controls. These findings suggest the need for
      rehabilitation health professionals to develop and implement culturally
      appropriate interventions to improve the HRQoL of caregivers of individuals with
      dementia in Colombia.

PMID- 20826709
TI  - Re: "overview of the cohort consortium vitamin D pooling project of rarer
      cancers".

PMID- 20826710
TI  - Japanese optic-spinal MS: is it MS or neuromyelitis optica and does the answer
      dictate treatment?

PMID- 20826711
TI  - IFNbeta-1b may severely exacerbate Japanese optic-spinal MS in neuromyelitis
      optica spectrum.
AB  - BACKGROUND: Interferon-beta-1b (IFNbeta-1b) has been used to prevent exacerbation
      of relapsing-remitting multiple sclerosis (RRMS) including optic-spinal multiple
      sclerosis (OSMS) in Japan. We encountered 2 patients with OSMS with unexpectedly
      severe exacerbation soon after the initiation of IFNbeta-1b therapy. The
      experience urged us to retrospectively review the patients with RRMS who had been
      treated with IFNbeta-1b to identify similar cases. METHODS: At neurologic
      departments of 9 hospitals, the medical records of 56 patients with RRMS were
      reviewed to identify those who showed severe exacerbation soon after the
      initiation of IFNbeta-1b therapy. RESULTS: Of 56 patients with RRMS, we
      identified 7 who experienced severe exacerbation (exacerbation with increased
      scores of Expanded Disability Status Scale ?7.0) within 90 days of the initiation
      of IFNbeta-1b therapy. In all 7 patients, the exacerbations after the initiation
      of IFNbeta-1b therapy were more severe than those experienced by the individual
      patients before the use of IFNbeta-1b, and seemed to have occurred unexpectedly
      in a short time after the initiation of INFbeta-1b therapy. A retrospective
      analysis revealed that all 7 patients had antibodies toward aquaporin 4, and the
      clinical features of all 7 patients after the exacerbation were consistent with
      those of neuromyelitis optica (NMO) spectrum. CONCLUSIONS: Our study suggests
      that IFNbeta-1b may trigger severe exacerbation in patients with the NMO
      spectrum. In INFbeta-1b therapy, cases in NMO spectrum should be carefully
      excluded.

PMID- 20826712
TI  - Anti-NMDA receptor encephalitis causing prolonged nonconvulsive status
      epilepticus.

PMID- 20826713
TI  - Optical coherence tomography: a sign of the times.

PMID- 20826714
TI  - Prior antiplatelet therapy and outcome following intracerebral hemorrhage: a
      systematic review.
AB  - OBJECTIVES: Antiplatelet therapy (APT) promotes bleeding; therefore, APT might
      worsen outcome in patients with intracerebral hemorrhage (ICH). We performed a
      systematic review and meta-analysis to address the hypothesis that pre-ICH APT
      use is associated with mortality and poor functional outcome following ICH.
      METHODS: The Medline and Embase databases were searched in February 2008 using
      relevant key words, limited to human studies in the English language. Cohort
      studies of consecutive patients with ICH reporting mortality or functional
      outcome according to pre-ICH APT use were identified. Of 2,873 studies screened,
      10 were judged to meet inclusion criteria by consensus of 2 authors.
      Additionally, we solicited unpublished data from all authors of cohort studies
      with >100 patients published within the last 10 years, and received data from 15
      more studies. Univariate and multivariable-adjusted odds ratios (ORs) for
      mortality and poor functional outcome were abstracted as available and pooled
      using a random effects model. RESULTS: We obtained mortality data from 25 cohorts
      (15 unpublished) and functional outcome data from 21 cohorts (14 unpublished).
      Pre-ICH APT users had increased mortality in both univariate (OR 1.41, 95%
      confidence interval [CI] 1.21 to 1.64) and multivariable-adjusted (OR 1.27, 95%
      CI 1.10 to 1.47) pooled analyses. By contrast, the pooled OR for poor functional
      outcome was no longer significant when using multivariable-adjusted estimates
      (univariate OR 1.29, 95% CI 1.09 to 1.53; multivariable-adjusted OR 1.10, 95% CI
      0.93 to 1.29). CONCLUSIONS: In cohort studies, APT use at the time of ICH
      compared to no APT use was independently associated with increased mortality but
      not with poor functional outcome.

PMID- 20826715
TI  - Think before you leap: donepezil reduces falls?

PMID- 20826716
TI  - EGFR gene copy number as a predictive biomarker for patients receiving tyrosine
      kinase inhibitor treatment: a systematic review and meta-analysis in non-small
      cell lung cancer.
AB  - INTRODUCTION: We conducted a systematic review and meta-analysis to assess
      epidermal growth factor receptor (EGFR) gene copy number as a potential biomarker
      of survival for patients with advanced non-small-cell lung cancer (NSCLC)
      receiving single-agent treatment with EGFR tyrosine kinase inhibitors (TKIs).
      METHODS: We systematically identified articles investigating EGFR gene copy
      number by fluorescent or chromogenic in situ hybridization in patients with
      advanced or recurrent NSCLC treated with the TKIs erlotinib or gefitinib, (last
      search: 31 June 2009). Eligible studies had to report on overall survival (OS),
      progression-free survival (PFS) or time-to-progression (TTP), stratified by EGFR
      gene copy number. Summary hazard ratios (HRs) were calculated using random
      effects models. RESULTS: Among 255 identified studies, 20 (1689 patients, 594
      with increased gene copy number), 10 (822 patients, 290 with increased gene copy
      number) and 5 (294 patients, 129 with increased gene copy number) were eligible
      for the OS, PFS and TTP meta-analyses, respectively. Increased EGFR gene copy
      number was associated with increased OS (HR = 0.77; 95% CI 0.66-0.89; P = 0.001),
      PFS (HR = 0.60; 95% CI 0.46-0.79; P<0.001) and TTP (HR = 0.50; 95% CI 0.28-0.91;
      P = 0.02). Among predominantly white populations, increased EGFR gene copy number
      was strongly associated with improved survival (HR = 0.70; 95% CI 0.59-0.82;
      P<0.001), whereas it did not influence survival in East Asians (HR = 1.11; 95% CI
      0.82-1.50; P=0.50). This difference was statistically significant (P=0.02).
      CONCLUSION: Among TKI-treated patients, increased EGFR gene copy number appears
      to be associated with improved survival outcomes. The effect on OS appears to be
      limited to patients of non-Asian descent.

PMID- 20826717
TI  - Detection, evaluation, and management of iron-restricted erythropoiesis.
AB  - Progress in our understanding of iron-restricted erythropoiesis has been made
      possible by important advances in defining the molecular mechanisms of iron
      homeostasis. The detection and diagnostic classification of iron-restricted
      erythropoiesis can be a challenging process for the clinician. Newer assays for
      markers of inflammation may allow more targeted management of the anemia in these
      conditions. The availability of new intravenous iron preparations provides new
      options for the treatment of iron-restricted erythropoiesis. This review
      summarizes recent advances regarding the detection, evaluation, and management of
      iron-restricted erythropoiesis.

PMID- 20826718
TI  - A PKA-Csk-pp60Src signaling pathway regulates the switch between endothelial cell
      invasion and cell-cell adhesion during vascular sprouting.
AB  - Angiogenesis is controlled by signals that stimulate motility in endothelial
      cells at the tips of vascular sprouts while maintaining cell-cell adhesion in the
      stalks of angiogenic sprouts. We show here that Gs-linked G protein-coupled
      receptor activation of cAMP-dependent protein kinase (PKA) plays an important
      role in regulating the switch between endothelial cell adhesion and migration by
      activating C-terminal Src kinase, leading to inhibition of pp60Src. Activated PKA
      blocks pp60Src-dependent vascular endot helial-cadherin phosphorylation, thereby
      stimulating cell-cell adhesion while suppressing endothelial cell polarization,
      motility, angiogenesis, and vascular permeability. Similar to the actions of
      Notch and Dll4, PKA activation blocks sprouting in newly forming embryonic blood
      vessels, while PKA inhibition promotes excessive sprouting in these vessels.
      These findings demonstrate that G protein-coupled receptors and PKA regulate
      vascular sprouting during angiogenesis by controlling endothelial cell migration
      and cell-cell adhesion through their actions on pp60Src.

PMID- 20826719
TI  - Randomized, double-blind trial of fluconazole versus voriconazole for prevention
      of invasive fungal infection after allogeneic hematopoietic cell transplantation.
AB  - Invasive fungal infection (IFI) is a serious threat after allogeneic
      hematopoietic cell transplant (HCT). This multicenter, randomized, double-blind
      trial compared fluconazole (N = 295) versus voriconazole (N = 305) for the
      prevention of IFI in the context of a structured fungal screening program.
      Patients undergoing myeloablative allogeneic HCT were randomized before HCT to
      receive study drugs for 100 days, or for 180 days in higher-risk patients. Serum
      galactomannan was assayed twice weekly for 60 days, then at least weekly until
      day 100. Positive galactomannan or suggestive signs triggered mandatory
      evaluation for IFI. The primary endpoint was freedom from IFI or death (fungal
      free survival; FFS) at 180 days. Despite trends to fewer IFIs (7.3% vs 11.2%; P =
      .12), Aspergillus infections (9 vs 17; P = .09), and less frequent empiric
      antifungal therapy (24.1% vs 30.2%, P = .11) with voriconazole, FFS rates (75% vs
      78%; P = .49) at 180 days were similar with fluconazole and voriconazole,
      respectively. Relapse-free and overall survival and the incidence of severe
      adverse events were also similar. This study demonstrates that in the context of
      intensive monitoring and structured empiric antifungal therapy, 6-month FFS and
      overall survival did not differ in allogeneic HCT recipients given prophylactic
      fluconazole or voriconazole. This trial was registered at www.clinicaltrials.gov
      as NCT00075803.

PMID- 20826720
TI  - Evidence that growth factor independence 1b regulates dormancy and peripheral
      blood mobilization of hematopoietic stem cells.
AB  - Donor-matched transplantation of hematopoietic stem cells (HSCs) is widely used
      to treat hematologic malignancies but is associated with high mortality. The
      expansion of HSC numbers and their mobilization into the bloodstream could
      significantly improve therapy. We report here that adult mice conditionally
      deficient for the transcription Growth factor independence 1b (Gfi1b) show a
      significant expansion of functional HSCs in the bone marrow and blood. Despite
      this expansion, Gfi1b(ko/ko) HSCs retain their ability to self-renew and to
      initiate multilineage differentiation but are no longer quiescent and contain
      elevated levels of reactive oxygen species. Treatment of Gfi1b(ko/ko) mice with N
      acetyl-cystein significantly reduced HSC numbers indicating that increased
      reactive oxygen species levels are at least partially responsible for the
      expansion of Gfi1b-deficient HSCs. Moreover, Gfi1b(-/-) HSCs show decreased
      expression of CXCR4 and Vascular cell adhesion protein-1, which are required to
      retain dormant HSCs in the endosteal niche, suggesting that Gfi1b regulates HSC
      dormancy and pool size without affecting their function. Finally, the additional
      deletion of the related Gfi1 gene in Gfi1b(ko/ko) HSCs is incompatible with the
      maintenance of HSCs, suggesting that Gfi1b and Gfi1 have partially overlapping
      functions but that at least one Gfi gene is essential for the generation of HSCs.

PMID- 20826721
TI  - IL-21 induces death of marginal zone B cells during chronic inflammation.
AB  - Interleukin-2 (IL-2) and IL-21 share activities in the control of T- and B-cell
      maturation, proliferation, function, and survival. However, opposing roles for IL
      2 and IL-21 have been reported in the development of regulatory T cells. To
      dissect unique, redundant, and opposing activities of IL-2 and IL-21, we compared
      T- and B-cell development and function in mice lacking both IL-2 receptor alpha
      (IL-2Ralpha) and IL-21R (double knockouts [DKO]) with single knockout and wild
      type (WT) mice. Similarly to il2ra(-/-) mice, DKO showed reduced numbers of
      regulatory T cells and, consequently, hyper-activation and proliferation of T
      cells associated with inflammatory disease (ie, colitis), weight loss, and
      reduced survival. The absence of IL-2Ralpha resulted in overproduction of IL-21
      by IFN-gamma-producing CD4(+) T cells, which induced apoptosis of marginal zone
      (MZ) B cells. Hence, MZ B cells and MZ B-cell immunoglobulin M antibody responses
      to Streptococcus pneumoniae phosophorylcholine were absent in il2ra(-/-) mice but
      were completely restored in DKO mice. Our results highlight key roles of IL-2 in
      inhibiting IL-21 production by CD4(+) T cells and of IL-21 in negatively
      regulating MZ B-cell survival and antibody production.

PMID- 20826722
TI  - Fancd2-/- mice have hematopoietic defects that can be partially corrected by
      resveratrol.
AB  - Progressive bone marrow failure is a major cause of morbidity and mortality in
      human Fanconi Anemia patients. In an effort to develop a Fanconi Anemia murine
      model to study bone marrow failure, we found that Fancd2(-/-) mice have readily
      measurable hematopoietic defects. Fancd2 deficiency was associated with a
      significant decline in the size of the c-Kit(+)Sca-1(+)Lineage(-) (KSL) pool and
      reduced stem cell repopulation and spleen colony-forming capacity. Fancd2(-/-)
      KSL cells showed an abnormal cell cycle status and loss of quiescence. In
      addition, the supportive function of the marrow microenvironment was compromised
      in Fancd2(-/-) mice. Treatment with Sirt1-mimetic and the antioxidant drug,
      resveratrol, maintained Fancd2(-/-) KSL cells in quiescence, improved the marrow
      microenvironment, partially corrected the abnormal cell cycle status, and
      significantly improved the spleen colony-forming capacity of Fancd2(-/-) bone
      marrow cells. We conclude that Fancd2(-/-) mice have readily quantifiable
      hematopoietic defects, and that this model is well suited for pharmacologic
      screening studies.

PMID- 20826723
TI  - Transferrin receptor 2 is a component of the erythropoietin receptor complex and
      is required for efficient erythropoiesis.
AB  - Erythropoietin (Epo) is required for erythroid progenitor differentiation.
      Although Epo crosslinking experiments have revealed the presence of Epo receptor
      (EpoR)-associated proteins that could never be identified, EpoR is considered to
      be a paradigm for homodimeric cytokine receptors. We purified EpoR-binding
      partners and identified the type 2 transferrin receptor (TfR2) as a component of
      the EpoR complex corresponding to proteins previously detected in cross-linking
      experiments. TfR2 is involved in iron metabolism by regulating hepcidin
      production in liver cells. We show that TfR2 and EpoR are synchronously
      coexpressed during the differentiation of erythroid progenitors. TfR2 associates
      with EpoR in the endoplasmic reticulum and is required for the efficient
      transport of this receptor to the cell surface. Erythroid progenitors from TfR2(
      /-)mice show a decreased sensitivity to Epo and increased circulating Epo levels.
      In human erythroid progenitors, TfR2 knockdown delays the terminal
      differentiation. Erythroid cells produce growth differentiation factor-15, a
      cytokine that suppresses hepatic hepcidin production in certain erythroid
      diseases such as thalassemia. We show that the production of growth
      differentiation factor-15 by erythroid cells is dependent on both Epo and TfR2.
      Taken together, our results show that TfR2 exhibits a non hepatic function as a
      component of the EpoR complex and is required for efficient erythropoiesis.

PMID- 20826724
TI  - Successful treatment of EBV-associated posttransplantation lymphoma after cord
      blood transplantation using third-party EBV-specific cytotoxic T lymphocytes.
AB  - Cellular therapy of Epstein-Barr virus (EBV)(+) posttransplantation
      lymphoproliferative diseases (PTLD) in cord blood transplant (CBT) recipients is
      limited by lack of donor access and the donor's naive neonatal immune system. We
      therefore used partially human leukocyte antigen-matched third-party in vitro
      expanded EBV-specific cytotoxic T lymphocytes (CTLs) to treat 2 CBT recipients
      with life-threatening, donor-derived monoclonal EBV(+) diffuse large B-cell
      lymphomas with extranodal involvement developing in the context of graft-versus
      host disease. Both patients had failed immunosuppression taper and Rituximab.
      After 5 and 9 infusions of 10(6) EBV-CTL/kg, respectively, each patient achieved
      a sustained complete remission without toxicity or graft-versus-host disease.
      Each is alive without recurrence at 20 and 15 months, respectively, post-EBV-PTLD
      diagnosis. This approach demonstrates the efficacy of using "off-the-shelf,"
      virus-specific third-party CTLs restricted by human leukocyte antigens expressed
      by the tumor to treat otherwise lethal EBV-PTLD. Such therapy may also be
      applicable to the treatment of other infections and residual or recurrent
      malignancy after CBT.

PMID- 20826725
TI  - Is the perfect mouse cloning experiment in sight?

PMID- 20826726
TI  - Increased expression of the Na,K-ATPase alpha4 isoform enhances sperm motility in
      transgenic mice.
AB  - The Na,K-ATPase alpha4 (ATP1A4) isoform is specifically expressed in male germ
      cells and is highly prevalent in spermatozoa. Although selective inhibition of
      alpha4 activity with ouabain has been shown to affect sperm motility, a more
      direct analysis of the role of this isoform in sperm movement has not yet been
      demonstrated. To establish this, we engineered transgenic mice that express the
      rat alpha4 isoform fused to green fluorescent protein in male germ cells, under
      the control of the mouse protamine 1 promoter. We showed that the rat Atp1a4
      transgene is expressed in mouse spermatozoa and that it is localized to the sperm
      flagellum. In agreement with increased expression of the alpha4 isoform, sperm
      from transgenic mice displayed higher alpha4-specific Na,K-ATPase activity and
      binding of fluorescently labeled ouabain than wild-type mice. In contrast,
      expression and activity of ATP1A1 (alpha1), the other Na,K-ATPase alpha isoform
      present in sperm, remained unchanged. Similar to wild-type mice, mice expressing
      the alpha4 transgene exhibited normal testis and sperm morphology and no
      differences in fertility. However, compared to wild-type mice, sperm from
      transgenic mice displayed plasma membrane hyperpolarization and higher total and
      progressive motility. Other parameters of motility also increased, including
      straight-line, curvilinear, and average path velocities and amplitude of lateral
      head displacement. In addition, sperm from the transgenic mice showed enhanced
      sperm hyperactive motility, but no changes in progesterone-induced acrosome
      reaction. Altogether, these results provide new genetic evidence for the role of
      the ATP1A4 isoform in sperm motility, under both noncapacitating and capacitating
      conditions.

PMID- 20826727
TI  - Temporal control of spermatogenesis is independent of the central circadian
      pacemaker in Djungarian hamsters (Phodopus sungorus).
AB  - In mammals, the duration of the cycle of the seminiferous epithelium (DCSE)
      largely differs between species, but is remarkably stable within a species,
      usually showing variations of 1%-3%. It is difficult to change the DCSE, e.g., by
      hormones or chemicals. Initial experiments, employing quantitative RT-PCR, aimed
      at investigating the diurnal profiles of the clock genes Arntl (previously called
      Bmal1) and Per1 in testes and kidneys of Djungarian hamsters (Phodopus sungorus).
      While the testicular levels of Arntl were almost constant, clear diurnal
      variations were identified for Per1. In order to clarify whether day length (T
      cycle) is a factor for DSCE, adult male hamsters (n = 20 per group) were exposed
      to normal (T = 24 h), prolonged (T = 25 h), or shortened (T = 23 h) T-cycles,
      with cycles thus being longer or shorter by 4.2% compared to the normal
      condition. Exposure lasted for 43 days, during which the activity of the animals
      was recorded to confirm entrainment. DCSE was estimated by incorporation of
      bromodeoxyuridine in dividing cells and the immunohistochemical localization of
      labeled cells in stages I-XII of the seminiferous epithelium. Despite the low
      variability of the results and the close agreement with previously published
      data, no effects of prolonged or shortened T-cycles on DCSE could be identified
      (24 h: 7.98 +/- 0.05 days; 23 h: 7.94 +/- 0.04 days; 25 h: 7.91 +/- 0.03 days; P
      > 0.05). The results strongly indicate that the high temporal precision of
      spermatogenesis is independent of the central circadian clock.

PMID- 20826728
TI  - In vivo treatments with fulvestrant and anastrozole differentially affect gene
      expression in the rat efferent ductules.
AB  - Estrogen plays a key role in maintaining the morphology and function of the
      efferent ductules. We previously demonstrated that the antiestrogen fulvestrant
      markedly affected gene expression in the rat efferent ductules. The mechanism of
      fulvestrant action to modulate gene expression may involve not only the blockade
      of ESR1 and ESR2 estrogen receptors, but also the activation of ESR1 and ESR2
      when the receptors are tethered to AP-1 or SP1 transcription factors, or the
      activation of the G protein-coupled estrogen receptor 1. We therefore compared
      the effects of two strategies to interfere with estrogen action in the rat
      efferent ductules: treatment with fulvestrant or with the aromatase inhibitor
      anastrozole. Whereas fulvestrant markedly increased Mmp7 and Spp1, and reduced
      Nptx1 mRNA levels, no changes were observed with anastrozole. Fulvestrant caused
      changes in epithelial morphology that were not seen with anastrozole. Fulvestrant
      shifted MMP7 immunolocalization in the epithelial cells from the supranuclear to
      the apical region; this effect was less pronounced with anastrozole. In vitro
      studies of (35)S-methionine incorporation showed that protein release was
      increased, whereas tissue protein content in the efferent ductules of fulvestrant
      treated rats was decreased. Although fulvestrant markedly affected gene
      expression, no changes were observed on AP-1 and SP1 DNA-binding activity. The
      blockade of ESRs seems to be the major reason explaining the differences between
      both treatments. At least some of the effects of fulvestrant appear to result
      from compensatory mechanisms activated by the dramatic changes caused by ESR1
      blockade.

PMID- 20826729
TI  - Direct effects of retinoic acid on entry of fetal male germ cells into meiosis in
      mice.
AB  - In both male and female germ cells of mice, retinoic acid (RA) is a meiosis
      inducing factor. In the present study, we used a germ cell culture system to
      examine the direct effects of RA on meiotic initiation in male germ cells at the
      stage when they normally enter mitotic arrest to determine the extent to which
      fetal male germ cells can respond to exogenous RA to alter their sex-specific
      pathway. Male germ cells between 13.5 and 15.5 days postcoitum (dpc) were
      isolated from Pou5fl-green fluorescent protein transgenic fetuses and cultured
      with or without RA for up to 6 days. In the absence of RA, male germ cells did
      not undergo DNA replication and did not enter meiosis in culture. However, in the
      presence of RA, male germ cells isolated at 13.5 dpc expressed Stra8 and
      initiated the meiotic process. The ratio of cells entering meiosis gradually
      decreased as cells were isolated progressively at later stages. By 15.5 dpc,
      isolated male germ cells lost their ability to respond to RA signaling. These
      cells remained dispersed as single cells and progressed along the male
      differentiation pathway, as evidenced by the establishment of male-specific
      methylation imprints regardless of the presence or absence of RA. We conclude
      that male germ cells maintain sexual bipotency until 14.5 dpc that can be
      reversed by the addition of RA. Once male germ cells enter mitotic arrest,
      however, they appear to be committed irreversibly to the male-specific
      differentiation pathway even in the presence of exogenously added RA.

PMID- 20826730
TI  - Lipopolysaccharide-induced epididymitis disrupts epididymal beta-defensin
      expression and inhibits sperm motility in rats.
AB  - Although more than 40 beta-defensins have been identified in rat epididymis,
      little is known about their regulation or their relation to male infertility
      caused by inflammation. Using a rat model of epididymitis induced by
      lipopolysaccharide (LPS), we examined expression of SPAG11E (also known as
      Bin1b), a caput epididymis-specific beta-defensin in rat. Unlike the expression
      of other beta-defensins in various epithelial cells with upregulated expression
      after LPS stimulation, expression of SPAG11E was significantly decreased by LPS
      at the mRNA and protein levels. LPS treatment also significantly decreased both
      sperm binding to SPAG11E and sperm motility, and supplementation of the
      spermatozoa with recombinant SPAG11E in vitro remarkably increased both SPAG11E
      binding and motility of sperm. To clarify whether decreased expression is a
      common pattern of epididymal beta-defensins after LPS stimulation, we examined
      the expression of another 12 epididymal beta-defensins expressed in the caput
      epididymis. For nine of these beta-defensins, expression was decreased, but for
      the other three, expression remained unaffected. These findings demonstrate that
      LPS-induced epididymitis can decrease the expression of epididymal beta-defensins
      and that disruption of SPAG11E expression is involved in the impairment of sperm
      motility.

PMID- 20826731
TI  - Neuromedin B and its receptor induce labor onset and are associated with the RELA
      (NFKB P65)/IL6 pathway in pregnant mice.
AB  - Although the neuromedin B receptor (NMBR), a bombesin receptor family member, has
      been implicated in thermoregulation and in stimulation of both urogenital and
      gastrointestinal smooth muscle contraction, its underlying role in labor onset
      and its associated molecular mechanisms remain poorly understood. We examined the
      relationship between temporal and spatial NMBR expression in the myometrium of
      pregnant mice and potential mechanistic pathways leading to labor onset.
      Resultant data indicate that NMBR expression peaked at term and before
      parturition. Maternal exposure to the NMBR agonist neuromedin B (NMB) shortened
      the gestational age of pups, an effect that was also observed after oxytocin
      administration. Both RELA (NFKB P65) DNA-binding activity and interleukin 6 (Il6)
      mRNA expression were greatest during parturition and after maternal exposure to
      the highest NMB concentration administered (150 MUg/kg). Furthermore, a
      significant correlation was observed among NMBR mRNA expression, RELA DNA-binding
      activity, and Il6 mRNA expression. These data demonstrate that NMB and its
      receptor can induce the onset of labor via a RELA/IL6-mediated pathway.

PMID- 20826732
TI  - Identification and expression of potential regulators of the mammalian mitotic-to
      meiotic transition.
AB  - Meiosis is unique to germ cells and occurs in a sex-specific manner. The genes
      regulating meiotic initiation in either sex are yet to be fully elucidated.
      Recent studies have revealed the importance of retinoic acid and one of its
      target genes, Stra8, in meiotic initiation in both sexes. Microarray analysis of
      whole murine embryonic ovary and postnatal testis time course data revealed a
      single peak of Stra8 expression in each organ at the onset of meiosis; at
      Embryonic Day 14.5 in the ovary and 10 days postpartum in the testis. In order to
      identify other genes involved in the initiation of meiosis in mammals, murine
      testis and ovary microarray data were examined more closely for transcripts with
      expression profiles similar to Stra8. Three such candidates include establishment
      of cohesion 1 homolog 2 (Esco2), encoding a protein essential for sister
      chromatid cohesion; SET domain, bifurcated 2 (Setdb2), the mouse ortholog of
      Eggless, which is essential for oogenesis in Drosophila; and ubiquitin-activating
      enzyme 6 (Uba6), a gene with fivefold higher expression in human and mouse testes
      than any other organ. In situ hybridization and immunohistochemistry or
      immunofluorescence were performed to localize Esco2, Setbd2, and Uba6 expression
      in the developing testis. The cellular expression pattern localized all three of
      these transcripts and their respective proteins to germ cells transitioning from
      mitosis to meiosis, hence supporting the hypothesis of their involvement in the
      initiation of meiosis. Future research will be directed at determining a specific
      role for these three proteins in germ cell differentiation.

PMID- 20826733
TI  - To screen or not to screen for Lynch syndrome.

PMID- 20826734
TI  - The hazards of endpoints.

PMID- 20826735
TI  - Drilling down to the causes of racial disparities in lung cancer.

PMID- 20826736
TI  - StatBite: Lynch syndrome increases the risk of various cancers.

PMID- 20826738
TI  - Calls for new reporting standards, quality control in microarrays.

PMID- 20826739
TI  - Time to study nurses, again.

PMID- 20826737
TI  - Improved endpoints for cancer immunotherapy trials.
AB  - Unlike chemotherapy, which acts directly on the tumor, cancer immunotherapies
      exert their effects on the immune system and demonstrate new kinetics that
      involve building a cellular immune response, followed by changes in tumor burden
      or patient survival. Thus, adequate design and evaluation of some immunotherapy
      clinical trials require a new development paradigm that includes reconsideration
      of established endpoints. Between 2004 and 2009, several initiatives facilitated
      by the Cancer Immunotherapy Consortium of the Cancer Research Institute and
      partner organizations systematically evaluated an immunotherapy-focused clinical
      development paradigm and created the principles for redefining trial endpoints.
      On this basis, a body of clinical and laboratory data was generated that supports
      three novel endpoint recommendations. First, cellular immune response assays
      generate highly variable results. Assay harmonization in multicenter trials may
      minimize variability and help to establish cellular immune response as a
      reproducible biomarker, thus allowing investigation of its relationship with
      clinical outcomes. Second, immunotherapy may induce novel patterns of antitumor
      response not captured by Response Evaluation Criteria in Solid Tumors or World
      Health Organization criteria. New immune-related response criteria were defined
      to more comprehensively capture all response patterns. Third, delayed separation
      of Kaplan-Meier curves in randomized immunotherapy trials can affect results.
      Altered statistical models describing hazard ratios as a function of time and
      recognizing differences before and after separation of curves may allow improved
      planning of phase III trials. These recommendations may improve our tools for
      cancer immunotherapy trials and may offer a more realistic and useful model for
      clinical investigation.

PMID- 20826740
TI  - The ultrafiltration coefficient of a dialyser (KUF) is not a fixed value, and it
      follows a parabolic function: the new concept of KUF max.
AB  - BACKGROUND: Hydraulic permeability (KUF) is an intrinsic characteristic of
      dialysers, reported by the manufacturer as a single value, which drives and
      limits fluid removal. High-flux dialysers have been introduced with the
      appearance of convective techniques, aiming to increase fluid and solute removal.
      High convective volumes are being employed, although their advantages have not
      been fully demonstrated. METHODS: We assessed KUF over a pre-selected range of
      ultrafiltration rates (QUF) in post-dilutional haemodiafiltration and high-flux
      haemodialysis. RESULTS: KUF vs QUF was neither a fixed value nor a linear
      function but followed a parabolic function with a vertex der (y)=0, which we have
      called KUF max. This also held true in high-flux routine dialysis. CONCLUSIONS:
      These findings are completely new and have clear applications in clinics. The
      vertex point might be used to define the optimal QUF of a dialysis system, which
      would be that obtained at KUF max and corresponds to the best QUF/transmembrane
      pressure ratio, as opposed to the maximum QUF (which corresponds to the highest
      possible QUF), frequently associated with haemoconcentration, clotting, loss in
      dialyser surface area, and treatment problems. Determining KUF max in vivo could
      be of help in dialysis prescription and control with automatic systems.

PMID- 20826741
TI  - Bortezomib: a new player in pre- and post-transplant desensitization?
AB  - Several desensitization strategies have been investigated for the reversal of
      acute antibody-mediated rejection or for the removal of preformed anti-HLA
      antibodies, with the aim to promote access to renal transplantation. Today, their
      success appears limited or incomplete. Bortezomib, a selective inhibitor of the
      26S proteasome, which is largely used in the treatment of multiple myeloma, could
      be a novel promising desensitizing agent. Its mechanism of action and preliminary
      clinical use in renal transplantation is reviewed here.

PMID- 20826742
TI  - Impact of iron treatment on immune effector function and cellular iron status of
      circulating monocytes in dialysis patients.
AB  - BACKGROUND: Iron is used as an adjunct therapy to treat anaemia in dialysis
      patients. However, iron may harbour detrimental effects in being a nutrient for
      invading pathogens or by modulating immune pathways. Thus, we prospectively
      studied the effects of iron treatment towards monocyte immune function. METHODS:
      Twenty-four haemodialysis patients in whom iron therapy was withheld for 2 weeks
      before study entry were randomly assigned to receive either a single parenteral
      dose of iron sucrose or saline (control), and the effects on iron status and
      immune function of patients' monocytes were analysed during follow-up. RESULTS:
      At baseline, we found an inverse relationship between serum ferritin levels and
      the inducibility of patients' monocytes for interleukin-6 and tumour necrosis
      factor-alpha formation following ex vivo immune stimulation. However, 48 h after
      intravenous iron administration, we observed a transient increase of tumour
      necrosis factor-alpha and interleukin-6 formation by unstimulated monocytes as
      compared with control subjects. This could be traced back to increased
      phosphorylation of nuclear factor kappa-B p65 in monocytes following iron
      treatment, which was more pronounced when pre-treatment serum ferritin levels
      were low. In parallel, intravenous iron injection resulted in storage of the
      metal in circulating monocytes as reflected by an increase of intracellular
      ferritin levels, and the amount of iron retention was positively associated with
      circulating concentrations of the iron regulatory peptide hepcidin. CONCLUSIONS:
      Intravenously administered iron is taken up by monocytes and leads to short-term
      activation of the nuclear factor kappa-B pathway. However, increased circulating
      ferritin levels are associated with an impaired immune response of monocytes. In
      addition, circulating hepcidin concentrations may determine the erythropoietic
      response to iron injection by modifying iron retention within monocytes.

PMID- 20826743
TI  - Role of thiamine status and genetic variability in transketolase and other
      pentose phosphate cycle enzymes in the progression of diabetic nephropathy.
AB  - BACKGROUND: Pentose phosphate pathway (PPP) represents a potentially 'protective'
      mechanism in hyperglycaemia due to shunting of glycolytic intermediates into PPP
      reactions. We hypothesized that thiamine status (plasma and erythrocyte levels of
      thiamine and its esters) together with genetic variability in key PPP enzymes
      transketolase (TKT), transaldolase and TKT-like-might contribute to the
      progression of diabetic nephropathy (DN) and mortality of diabetics. METHODS: A
      total of 240 diabetic subjects with variable degree of kidney disease were
      included at baseline and were followed up for a median of 26 (IQR 21-50) months.
      Concentrations of thiamine in plasma and whole blood and TKT-catalysed reaction
      were determined by HPLC. Single-nucleotide polymorphisms (SNPs) (n = 14) were
      genotyped by means of PCR using TaqMan chemistry (Applied Biosystems, Foster
      City, CA, USA). RESULTS: Significant differences in pTh, pThDP, eryThDP and
      eryTKT between DN-stage groups were ascertained (P < 0.05) with advancing stage
      of DN being accompanied with increasing values of pTh, pThDP and eryTKT but not
      eryThDP. A highly significant negative correlation (r = - 0.41, P < 0.001) was
      found between pThDP and eryThDP, and the tertiles of the ratio of eryThDP/pThDP
      were significantly associated with all-cause mortality rates (P = 0.0072). We
      also identified significant differences in the rate of DN progression between
      different pTDP tertile groups (P = 0.0017). No significant genetic effects were
      found. CONCLUSIONS: The results support the role of 'functional' thiamine
      deficiency in the development of hyperglycaemia-related pathology. Limited
      intracellular availability of active TKT co-factor seems to be a dominant
      abnormality.

PMID- 20826744
TI  - Normoalbuminaemia is associated with IgA nephropathy in primary glomerulopathy
      with nephrotic-range proteinuria in Chinese patients.
AB  - BACKGROUND: Massive proteinuria is often associated with hypoalbuminaemia in
      glomerulopathy. However, patients may have normal levels of serum albumin despite
      heavy proteinuria in many circumstances. This study analysed factors affecting
      serum levels of albumin in primary glomerulopathy patients with nephrotic-range
      proteinuria. METHODS: The renal histopathological data of 780 consecutive adult
      patients (age >= 18 years old) with primary glomerulopathy and nephrotic-range
      proteinuria, who received native renal biopsies in Peking University First
      Hospital from 1998 to 2007, were retrospectively analysed. RESULTS: Compared with
      patients with hypoalbuminaemia (serum albumin < 30 g/L), patients without
      hypoalbuminaemia were significantly younger (P < 0.001) and had significantly
      lower levels of proteinuria (P < 0.001). Patients without hypoalbuminaemia had a
      significantly higher proportion of IgA nephropathy (66.0% vs. 17.2%, P < 0.001).
      The independent predictors of hypoalbuminaemia in nephrotic-range proteinuria
      patients included age, gender, interval between onset of the disease and renal
      biopsy, proteinuria level, and pathological type of glomerulopathy. A serum level
      of albumin >= 35 g/L could predict IgA nephropathy with a specificity of 95.8%,
      and specificity increased with age. CONCLUSIONS: Among patients with primary
      glomerulopathy and nephrotic-range proteinuria, normoalbuminaemia is associated
      with IgA nephropathy.

PMID- 20826745
TI  - High prevalence of renal dysfunction in children after liver transplantation: non
      invasive diagnosis using a cystatin C-based equation.
AB  - BACKGROUND: Chronic kidney disease (CKD) has been increasingly shown to be a
      negative prognostic factor after liver transplantation (Ltx). Creatinine-based
      glomerular filtration rate (GFR) formulas are notoriously insensitive. In
      children, non-invasive determination of GFR by measurement of serum cystatin C is
      feasible and repeatedly correlated to the gold standards of GFR measurements. The
      aim of our study was to determine GFR using cystatin C (GFR(cys)) in comparison
      with conventional calculated creatinine clearance (GFR(crea)) in the long-term
      follow-up after paediatric liver transplantation (pLtx) in a large number of
      patients. METHODS: GFR of 168 children following liver transplantation was
      determined using cystatin C (GFR(cys)) and the Schwartz formula (GFR(crea)). In
      order to evaluate risk factors for CKD, a logistic regression analysis was
      performed. A multivariate model was applied to assess the impact of
      immunosuppressive treatment. RESULTS: The mean follow-up after transplantation
      was 7.8 (0.44-15.72) years. Due to a high overestimation of GFR as demonstrated
      in a Bland-Altman plot, only three patients with CKD stages 2-3 were detected
      with GFR(crea) compared with 34 with GFR(cys) (P < 0.001). Thus, prevalence of
      CKD with GFR((cys)) < 90 mL/min/1.73 m2; was 30.4%, 7.6% and 27% in patients with
      5, 10 and > 10 years of follow-up, respectively. Patients on cyclosporine had a
      significantly lower GFR than patients on tacrolimus. Logistic regression analysis
      did not show any significant risk factor for the development of CKD. CONCLUSIONS:
      The cystatin C equation is a non-invasive and sensitive diagnostic tool to detect
      renal dysfunction in children after Ltx at an early stage. The choice of first
      line calcineurin inhibitor has an important impact on the development of CKD.

PMID- 20826746
TI  - Effect of nephrotic syndrome on homocysteine metabolism.
AB  - BACKGROUND: Proteinuria and hyperhomocysteinaemia are independently associated
      with increased risk of atherosclerosis and cardiovascular disease. The available
      data on plasma homocysteine (Hcy) level in patients with nephrotic syndrome (NS)
      are contradictory with increased, decreased and unchanged values reported by
      different investigators. The majority of Hcy in the plasma is bound to albumin
      whose urinary losses and diminished plasma concentration are the defining
      features of NS. The present study was designed to explore the effect of NS on
      plasma concentration and urinary excretion of Hcy and hepatic expression of
      methylenetetrahydrofolate reductase (MTHFR) and cystathionine-beta-synthase
      (CBS), the key enzymes in re-methylation and trans-sulphuration of Hcy,
      respectively. METHODS: Sprague-Dawley rats were rendered nephrotic by IP
      injection of puromycin aminonucleoside. Urine and plasma were used for
      measurement of Hcy, and the liver was processed for assessment of MTHFR and CBS
      protein expression. RESULTS: Compared with the controls, nephrotic rats showed
      heavy proteinuria, hypoalbuminaemia, hypercholesterolaemia, normal plasma
      creatinine and creatinine clearance, reduced plasma Hcy, increased urinary Hcy,
      and downregulation of CBS but not MTHFR expression. Plasma Hcy correlated
      directly with plasma albumin and inversely with urinary protein excretion. The
      urinary Hcy excretion correlated directly with urine protein excretion.
      CONCLUSIONS: NS results in significant reduction in plasma total Hcy
      concentration which is due to the reduction in albumin-bound Hcy as opposed to
      the free Hcy fraction. This is coupled with increased urinary excretion of
      albumin-bound Hcy. In addition, NS results in down-regulation of CBS which can
      curtail conversion of Hcy to cysteine and reduce production of H(2)S which is an
      important endogenous signalling molecule.

PMID- 20826747
TI  - HIV-1 Nef disrupts maturation of CD4+ T cells through CD4/Lck modulation.
AB  - The HIV-1 Nef protein is a major determinant of HIV-1 pathogenicity. It has been
      found to induce thymocyte depletion, but the mechanisms involved are not
      completely understood. Also, nothing is known about its effects on thymocyte
      selection. We used the CD4C/HIV(Nef) transgenic (Tg) mice, which develop a
      profound CD4(+) T cell lymphopenia, to study their thymic development. We report
      that HIV-1 Nef causes depletion of double-positive thymocytes and impairs
      selection and lineage commitment of CD4(+) single-positive thymocytes. This
      latter defect could be relieved by increasing the affinity of the TCR-MHC
      interaction or by allowing CD4(+) T cell maturation to proceed in absence of the
      CD4 tail, in double-Tg (Nef * CD4(tailless)) mice or in the presence of
      constitutively active Tg Lck(Y505F). These rescue strategies also resulted in
      reversal of peripheral CD4(+) T cell lymphopenia. Our data indicate that
      impairment of Lck-mediated CD4 coreceptor signaling by Nef is an important in
      vivo mechanism of HIV-1 pathogenesis.

PMID- 20826749
TI  - The origin and maturity of dendritic cells determine the pattern of sphingosine 1
      phosphate receptors expressed and required for efficient migration.
AB  - Dendritic cells (DCs) represent the most potent inducers of adaptive immune
      responses. Depending on their activation phenotype, DCs drive naive T cells into
      distinct differentiation pathways. To achieve this, DCs are present in virtually
      all tissues where they sample Ag and migrate to the T cell areas of lymph nodes
      (LNs) and spleen. Ample evidence exists demonstrating that sphingosine 1
      phosphate (S1P) is an important modulator of these processes, exerting its
      effects by binding to the S1P receptor S1P(1) and/or S1P(3). However, published
      data are contradictory, in part. We show in this study that the expression
      pattern, as well as the regulation of the S1P receptors, differs among in vitro
      generated DCs experiencing different kinds and duration of stimuli. Moreover, the
      influence of S1P(1) and S1P(3) on the in vivo migration of maturing DCs depends
      on the origin of these cells. Thus, in vitro-generated DCs require S1P(1) and
      S1P(3) to accomplish this, whereas skin-derived DCs migrate unhindered in the
      absence of S1P(3) but not when S1P(1) signaling is blocked. Migration of lamina
      propria DCs to the mesenteric LNs depends on S1P(1) and S1P(3). In contrast,
      relocation of maturing spleen-resident DCs to the T cell zone is independent of
      S1P(1) and S1P(3). However, intrasplenic positioning of immature DCs to the
      bridging channels depends on S1P(1) activity, with no noticeable contribution of
      S1P(3). These observations reveal a tissue-dependent contribution of S1P(3) to DC
      migration and suggest a fundamental role for S1P(1) for maturing DCs migrating
      from periphery to draining LNs.

PMID- 20826748
TI  - TLR4 and TLR5 on corneal macrophages regulate Pseudomonas aeruginosa keratitis by
      signaling through MyD88-dependent and -independent pathways.
AB  - Pseudomonas aeruginosa is a major cause of blindness and visual impairment in the
      United States and worldwide. Using a murine model of keratitis in which abraded
      corneas are infected with P. aeruginosa parent and DeltafliC (aflagellar) strains
      19660 and PAO1, we found that F4/80(+) macrophages were the predominant cell type
      in the cornea expressing TLR2, TLR4, and TLR5. Depletion of macrophages and
      dendritic cells using transgenic Mafia mice, in which Fas ligand is selectively
      activated in these cells, resulted in diminished cytokine production and cellular
      infiltration to the corneal stroma and unimpaired bacterial growth. TLR4(-/-)
      mice showed a similar phenotype postinfection with DeltafliC strains, whereas
      TLR4/5(-/-) mice were susceptible to corneal infection with parent strains. Bone
      marrow-derived macrophages stimulated with DeltafliC bacteria induced Toll/IL-1R
      intracellular domain (TIR)-containing adaptor inducing IFN-beta (TRIF)-dependent
      phosphorylation of IFN regulatory factor 3 in addition to TIR-containing adaptor
      protein/MyD88-dependent phosphorylation of IkappaB and nuclear translocation of
      the p65 subunit of NFkappaB. Furthermore, TRIF(-/-) mice showed a similar
      phenotype as TLR4(-/-) mice in regulating only DeltafliC bacteria, whereas MyD88(
      /-) mice were unable to clear parent or DeltafliC bacteria. Finally, IL-1R1(-/-)
      and IL-1alpha/beta(-/-) mice were highly susceptible to infection. Taken
      together, these findings indicate that P. aeruginosa activates TLR4/5 on resident
      corneal macrophages, which signal through TRIF and TIR-containing adaptor
      protein/MyD88 pathways, leading to NF-kappaB translocation to the nucleus,
      transcription of CXCL1 and other CXC chemokines, recruitment of neutrophils to
      the corneal stroma, and subsequent bacterial killing and tissue damage. IL-1alpha
      and IL-1beta are also produced, which activate an IL-1R1/MyD88-positive feedback
      loop in macrophages and IL-1R on other resident cells in the cornea.

PMID- 20826750
TI  - Mechanisms regulating monocyte CXCL8 secretion in neurocysticercosis and the
      effect of antiparasitic therapy.
AB  - Neurocysticercosis (NCC) due to infection with Taenia solium is a major cause of
      epilepsy worldwide. Larval degeneration, which may follow antiparasitic
      treatment, results in clinical symptoms due to inflammatory cell influx.
      Mechanisms regulating this are not well understood, but chemokines have a key
      role. Stimulation of human monocytes by cyst Ags from NCC-infected pigs showed
      that scolex and membrane Ags drive CXCL8 and CCL2 secretion. Antiparasitic
      treatment of pigs increased CXCL8 in response to brain, but not muscle, cyst Ags.
      Cyst-fluid Ags did not elicit monocyte chemokine secretion, inhibited LPS-induced
      CXCL8 by up to 89%, but did not alter CCL2 secretion. This effect was inhibited
      by anti-IL-10 Abs. Plasma CXCL8, TNF-alpha, IL-10, eotaxin, IL-1, IL-1ra, soluble
      IL-1R-II, and soluble TNFR-I and -II levels were evaluated in 167 NCC patients.
      Patients had lower plasma CXCL8 and TNF-alpha concentrations than control
      subjects. In summary, larval Ags from brain and muscle cysts differentially
      regulate chemokine secretion. Cyst-fluid inhibits CXCL8, and this is blocked by
      anti-IL-10 Abs. CXCL8 concentrations are decreased in patient plasma. Following
      anti-parasitic therapy, scolex and membrane Ags are exposed, and cyst fluid is
      decreased, leading to inflammatory cell influx. Taken together, the cellular,
      porcine, and human data may explain, in part, why NCC is usually asymptomatic but
      may cause proinflammatory symptoms, particularly following treatment.

PMID- 20826751
TI  - Vitamin D3 upregulated protein 1 suppresses TNF-alpha-induced NF-kappaB
      activation in hepatocarcinogenesis.
AB  - Vitamin D(3) upregulated protein 1 (VDUP1) is a candidate tumor suppressor, the
      expression of which is dramatically reduced in various tumor tissues. In this
      study, we found that VDUP1 expression is suppressed during human hepatic
      carcinogenesis, and mice lacking VDUP1 are much more susceptible to
      diethylnitrosamine-induced hepatocarcinogenesis compared with wild type mice.
      VDUP1-deficient tumors proliferated significantly more than wild type tumors and
      had corresponding changes in the expression of key cell cycle regulatory
      proteins. In addition, the hepatomitogen-induced response was associated with a
      considerable increase in the release of TNF-alpha and subsequent enhancement of
      NF-kappaB activation in VDUP1-deficient mice. When cells were treated with TNF
      alpha, the VDUP1 level was markedly reduced, concomitant with elevated NF-kappaB
      activation. Furthermore, the overexpression of VDUP1 resulted in the robust
      suppression of TNF-alpha-activated NF-kappaB activity via association with HDAC1
      and HDAC3. These results indicate that VDUP1 negatively regulates
      hepatocarcinogenesis by suppressing TNF-alpha-induced NF-kappaB activation.

PMID- 20826752
TI  - Phosphoinositide 3-kinase activity in T cells regulates the magnitude of the
      germinal center reaction.
AB  - The generation of high-affinity Abs is essential for immunity and requires
      collaboration between B and T cells within germinal centers (GCs). By using novel
      mouse models with a conditional deletion of the p110delta catalytic subunit of
      the PI3K pathway, we established that p110delta is required in T cells, but not
      in B cells, for the GC reaction. We found the formation of T follicular helper
      (T(FH)) cells to be critically dependent on p110delta in T cells. Furthermore, by
      deleting phosphatase and tensin homolog deleted on chromosome 10, which opposes
      p110delta in activated T cells, we found a positive correlation between increased
      numbers of T(FH) cells and GC B cells. These results are consistent with the
      hypothesis that T cell help is the limiting factor in the GC reaction. P110delta
      was not required for the expression of B cell lymphoma 6, the downregulation of
      CCR7, or T cell entry into primary follicles. Instead, p110delta was the critical
      catalytic subunit for ICOS downstream signaling and the production of key T(FH)
      cytokines and effector molecules. Our findings support a model in which the
      magnitude of the GC reaction is controlled by the activity of the PI3K pathway in
      T(FH) cells.

PMID- 20826753
TI  - Leishmania donovani promastigotes evade the antimicrobial activity of neutrophil
      extracellular traps.
AB  - Upon their recruitment to a site of infection and their subsequent activation,
      neutrophils release DNA and a subset of their granule content to form filamentous
      structures, known as neutrophil extracellular traps, which capture and kill
      microorganisms. In this study, we show that Leishmania promastigotes induced the
      rapid release of neutrophil extracellular traps from human neutrophils and were
      trapped by these structures. The use of Leishmania mutants defective in the
      biosynthesis of either lipophosphoglycan or GP63 revealed that these two major
      surface promastigote virulence determinants were not responsible for inducing the
      release of the surface protease neutrophil extracellular traps. We also
      demonstrate that this induction was independent of superoxide production by
      neutrophils. Finally, in contrast to wild-type Leishmania donovani promastigotes,
      mutants defective in lipophosphoglycan biosynthesis were highly susceptible to
      the antimicrobial activity of neutrophil extracellular traps. Altogether, our
      data suggest that neutrophil extracellular traps may contribute to the
      containment of L. donovani promastigotes at the site of inoculation, thereby
      facilitating their uptake by mononuclear phagocytes.

PMID- 20826754
TI  - Shedding of large functionally active CD11/CD18 Integrin complexes from leukocyte
      membranes during synovial inflammation distinguishes three types of arthritis
      through differential epitope exposure.
AB  - CD18 integrins are adhesion molecules expressed on the cell surface of leukocytes
      and play a central role in the molecular mechanisms supporting leukocyte
      migration to zones of inflammation. Recently, it was discovered that CD11a/CD18
      is shed from the leukocyte surface in models of inflammation. In this study, we
      show that shedding of human CD11/CD18 complexes is a part of synovial
      inflammation in rheumatoid arthritis and spondyloarthritis but not in
      osteoarthritis. In vivo and in vitro data suggest that the shedding is driven by
      TNF-alpha, which links the process to central events in the inflammatory
      response. The shed complexes contain multiple heterodimers of CD11/CD18, are
      variable in size, and differ according to the type of synovial inflammation.
      Furthermore, the differential structures determine the avidity of binding of the
      complexes to the ICAM-1. With the estimated concentrations of CD11/CD18 in plasma
      and synovial fluid a significant coverage of binding sites in ICAM-1 for CD18
      integrins is expected. Based on cell adhesion experiments in vitro, we
      hypothesize that the large soluble complexes of CD11/CD18 act in vivo to buffer
      leukocyte adhesion by competing with the membrane-bound receptors for ICAM-1
      binding sites. As reported here for synovial inflammation changes in the
      concentration or structure of these complexes should be considered as likely
      contributors to disease activity.

PMID- 20826755
TI  - Factor H facilitates adherence of Neisseria gonorrhoeae to complement receptor 3
      on eukaryotic cells.
AB  - Neisseria gonorrhoeae can engage human complement receptor 3 (CR3) directly or
      through surface-bound iC3b. Factor H (fH) that binds to bacteria facilitates
      conversion of C3b to iC3b. fH also binds directly to CR3 on professional
      phagocytes. Certain nonprofessional phagocytes, such as primary cervical
      epithelial cells, also express CR3. We hypothesized that fH could bridge bacteria
      to CR3 and facilitate gonococcal association with host cells. Specificity of the
      fH-CR3 interaction was confirmed using human CR3-transfected Chinese hamster
      ovary (CHO-CR3) cells. Using recombinant proteins that comprised contiguous fH
      domains (fH contains 20 short consensus repeat [SCR] domains) fused to murine Fc,
      we observed strong binding through SCRs 18-20, whereas weaker binding occurred
      through SCRs 6-10. Both regions also bound to unsialylated porin (Por) B.1A
      expressing N. gonorrhoeae. Accordingly, fH-related protein 1 (three of its five
      SCRs are highly homologous to fH SCRs 18-20) bound to CHO-CR3 and to unsialylated
      PorB.1A gonococci. An alternatively spliced variant of fH called fH-like protein
      1 (contains fH SCRs 1-7) bound to gonococci but minimally to CHO-CR3. An fH SCRs
      6-20 construct enhanced binding of unsialylated PorB.1A gonococci to CHO-CR3.
      However, a construct that contained only the apparently relevant SCRs (6, 7, and
      18-20) bound to CHO-CR3 and to gonococci separately, but did not enhance bacteria
      CR3 interactions, suggesting that the intervening SCRs (8-17) may impart a
      configurational and spatial requirement for fH to bridge gonococci to CR3. These
      results indicate adherence between fH-coated gonococci and CR3 and may provide a
      means for gonococci to gain sanctuary into nonprofessional phagocytes.

PMID- 20826756
TI  - Prolactin-induced production of reactive oxygen species and IL-1beta in
      leukocytes from the bony fish gilthead seabream involves Jak/Stat and NF-kappaB
      signaling pathways.
AB  - Prolactin (PRL), a peptide hormone produced by the pituitary gland, was shown to
      play an important role in the modulation of the immune system of lower and higher
      vertebrates. To further investigate the effects of PRL on the activation of
      professional phagocytes of bony fish, we stimulated head kidney leukocytes and
      purified macrophages from the gilthead seabream (Sparus aurata L.) with various
      physiological concentrations of native salmon PRL for 2 and 16 h and analyzed the
      respiratory burst activity and proinflammatory cytokine expression profile. The
      results showed that PRL was able to induce the production of reactive oxygen
      species and the expression of IL-1beta and TNF-alpha in a similar way to two
      major pathogen-associated molecular patterns: polyinosinic-polycytidylic acid and
      genomic DNA from the bacterium Vibrio anguillarum. Interestingly, when the
      leukocytes were stimulated with suboptimal concentrations of PRL in the presence
      of bacterial DNA, the expression of IL-1beta was synergistically induced. More
      importantly, all PRL activities were blocked by neutralizing Abs to PRL, as well
      as by pharmacological inhibitors of the Jak/Stat and NF-kappaB signaling
      pathways. In addition, EMSA and HPLC/mass spectrometry further confirmed that
      Stat and NF-kappaB were involved in the activation of seabream leukocytes by PRL.
      Collectively, our data identified PRL as a key regulator of the activation of
      fish professional phagocytes and demonstrated a cross-talk between TLR/NF-kappaB
      and PRLR/Jak/Stat signaling pathways. In addition, to the best of our knowledge,
      this is the first report showing that PRL modulates the activation of phagocyte
      NADPH oxidase through the Jak/Stat pathway in vertebrates.

PMID- 20826758
TI  - Cell surface heparan sulfate proteoglycans influence MHC class II-restricted
      antigen presentation.
AB  - Heparan sulfate proteoglycans (HSPGs) are glycoproteins ubiquitously distributed
      on the cell surface and in the extracellular matrix. Their heparan sulfate
      moieties often represent alternative attachment points for extracellular proteins
      that target specific receptors. Thus, HSPGs modulate ligand-receptor encounters
      and participate in numerous biological processes. In this study, we examined
      whether HSPGs can also influence MHC class II-restricted Ag presentation. We
      selected a heparan sulfate ligand derived from the HIV-1 Tat protein and coupled
      it to a model protein Ag. We showed that coupling of the Tat fragment makes the
      Ag capable of binding cells, including APCs, and increases its ability to
      stimulate specific T cells up to 180-fold. The boosting effect depends on Ag
      processing; it vanished in the presence of an excess of heparin or free Tat
      fragment, indicating that HSPGs can behave as receptors involved in MHC class II
      processing and presentation. Furthermore, with FcgammaRII-bearing APCs, immune
      complexes containing the coupled Ag stimulated T cells up to 700-fold more
      efficiently than Ag-containing immune complexes. This effect vanished in the
      presence of heparin and is not found with FcgammaRII(-) APCs, indicating that
      HSPGs can also behave as coreceptors during FcgammaRIIR-mediated Ag presentation.
      These results indicate that ubiquitous receptors, such as HSPGs, can influence
      MHC class II-restricted Ag presentation and suggest that proteins will be
      supported more efficiently by the immune system if they have the inherent
      capacity to bind heparan sulfate.

PMID- 20826757
TI  - GB virus type C envelope protein E2 elicits antibodies that react with a cellular
      antigen on HIV-1 particles and neutralize diverse HIV-1 isolates.
AB  - Broadly neutralizing Abs to HIV-1 are well described; however, identification of
      Ags that elicit these Abs has proven difficult. Persistent infection with GB
      virus type C (GBV-C) is associated with prolonged survival in HIV-1-infected
      individuals, and among those without HIV-1 viremia, the presence of Ab to GBV-C
      glycoprotein E2 is also associated with survival. GBV-C E2 protein inhibits HIV-1
      entry, and an antigenic peptide within E2 interferes with gp41-induced membrane
      perturbations in vitro, suggesting the possibility of structural mimicry between
      GBV-C E2 protein and HIV-1 particles. Naturally occurring human and
      experimentally induced GBV-C E2 Abs were examined for their ability to neutralize
      infectious HIV-1 particles and HIV-1-enveloped pseudovirus particles. All GBV-C
      E2 Abs neutralized diverse isolates of HIV-1 with the exception of rabbit anti
      peptide Abs raised against a synthetic GBV-C E2 peptide. Rabbit anti-GBV-C E2 Abs
      neutralized HIV-1-pseudotyped retrovirus particles but not HIV-1-pseudotyped
      vesicular stomatitis virus particles, and E2 Abs immune-precipitated HIV-1 gag
      particles containing the vesicular stomatitis virus type G envelope, HIV-1
      envelope, GBV-C envelope, or no viral envelope. The Abs did not neutralize or
      immune-precipitate mumps or yellow fever viruses. Rabbit GBV-C E2 Abs inhibited
      HIV attachment to cells but did not inhibit entry following attachment. Taken
      together, these data indicate that the GBV-C E2 protein has a structural motif
      that elicits Abs that cross-react with a cellular Ag present on retrovirus
      particles, independent of HIV-1 envelope glycoproteins. The data provide evidence
      that a heterologous viral protein can induce HIV-1-neutralizing Abs.

PMID- 20826759
TI  - Context-dependent regulation of hematopoietic lineage choice by HEBAlt.
AB  - Hematopoietic development is controlled by combinatorial interactions between E
      protein transcription factors and other lineage regulators that operate in the
      context of gene-regulatory networks. The E-proteins HEB and E2A are critical for
      T cell and B cell development, but the mechanisms by which their activities are
      directed to different genes in each lineage are unclear. We found that a short
      form of HEB, HEBAlt, acts downstream of Delta-like (DL)-Notch signaling to
      promote T cell development. In this paper, we show that forced expression of
      HEBAlt in mouse hematopoietic progenitors inhibited B cell development, but it
      allowed them to adopt a myeloid fate. HEBAlt interfered with the activity of E2A
      homodimers and with the expression of the transcription factor Pax5, both of
      which are critical for B cell development. However, when combined with DL-Notch
      signaling, HEBAlt enhanced the generation of T cell progenitors at the expense of
      myeloid cells. The longer form of HEB, HEBCan, also inhibited E47 activity and
      Pax5 expression, but it did not collaborate with DL-Notch signaling to suppress
      myeloid potential. Therefore, HEBAlt can suppress B cell or myeloid potential in
      a context-specific manner, which suggests a role for this factor in maintaining T
      lineage priming prior to commitment.

PMID- 20826760
TI  - HMGB1 inhibits macrophage activity in efferocytosis through binding to the
      alphavbeta3-integrin.
AB  - Phagocytosis of apoptotic cells is critical to resolution of inflammation. High
      mobility group box 1 protein (HMGB1), a mediator of inflammation, has been shown
      to diminish phagocytosis through binding to phosphatidylserine (PS) exposed on
      the surface of apoptotic neutrophils. However, it is currently unknown whether
      HMGB1 also modulates the activity of receptors involved in PS recognition on the
      surface of phagocytes. In the present studies, we found that preincubation of
      macrophages with HMGB1 decreased their ability to engulf apoptotic neutrophils or
      thymocytes. Preincubation of macrophages with HMGB1 prevented the enhancement of
      efferocytosis resulting from exposure to milk fat globule EGF factor 8 (MFG-E8),
      an opsonin that bridges PS and alpha(v)beta(3) as well as alpha(v)beta(5)
      integrins on the surface of phagocytes. The inhibitory effect of HMGB1 on the
      phagocytic activity of macrophages was prevented by preincubation of HMGB1 with
      soluble alpha(v)beta(3), but not with soluble alpha(v)beta(5). HMGB1 colocalized
      with the beta(3)-integrin on the cell membrane of macrophages and bound to
      soluble alpha(v)beta(3), but not to soluble alpha(v)beta(5). HMGB1 suppressed the
      interaction between MFG-E8 and alpha(v)beta(3). HMGB1 also inhibited
      intracellular signaling events, including ERK phosphorylation and Rac-1
      activation, which are activated in macrophages during phagocytosis of apoptotic
      cells. These results demonstrate that HMGB1 blocks alpha(v)beta(3)-dependent
      recognition and uptake of apoptotic cells.

PMID- 20826761
TI  - Disruption of PICK1 attenuates the function of ASICs and PKC regulation of ASICs.
AB  - Acid-sensing ion channels (ASICs) extensively exist in both central and
      peripheral neuronal systems and contribute to many physiological and pathological
      processes. The protein that interacts with C kinase 1 (PICK1) was cloned as one
      of the proteins interacting with protein kinase C (PKC) and colocalized with
      ASIC1 and ASIC2. Here, we used PICK1 knockout (PICK1-KO) C57/BL6 mice together
      with the whole cell patch clamp, calcium imaging, RT-PCR, Western blot, and
      immunocytochemistry techniques to explore the possible change in ASICs and the
      regulatory effects of PKC on ASICs. The results showed that PICK1 played a key
      role in regulation of ASIC functions. In PICK1-KO mouse cortical neurons, both
      the amplitude of ASIC currents and elevation of [Ca(2+)](i) mediated by acid were
      decreased, which were attributable to the decreased expression of ASIC1a and
      ASIC2a proteins in the plasma membrane. PKC, a partner protein of PICK1,
      regulated ASIC functions via PICK1. The agonist and antagonist of PKC only
      altered ASIC currents and acid-induced increase in [Ca(2+)](i) in wild-type, but
      not in KO mice. In conclusion, our data provided the direct evidence from PICK1
      KO mice that a novel target protein, PICK1, would regulate ASIC function and
      membrane expression in the brain. In addition, PICK1 played the bridge role
      between PKC and ASICs.

PMID- 20826762
TI  - Functional expression of SGLTs in rat brain.
AB  - This work provides evidence of previously unrecognized uptake of glucose via
      sodium-coupled glucose transporters (SGLTs) in specific regions of the brain. The
      current understanding of functional glucose utilization in brain is largely based
      on studies using positron emission tomography (PET) with the glucose tracer 2
      deoxy-2-[F-18]fluoro-D-glucose (2-FDG). However, 2-FDG is only a good substrate
      for facilitated-glucose transporters (GLUTs), not for SGLTs. Thus, glucose
      accumulation measured by 2-FDG omits the role of SGLTs. We designed and
      synthesized two high-affinity tracers: one, alpha-methyl-4-[F-18]fluoro-4-deoxy-D
      glucopyranoside (Me-4FDG), is a highly specific SGLT substrate and not
      transported by GLUTs; the other one, 4-[F-18]fluoro-4-deoxy-D-glucose (4-FDG), is
      transported by both SGLTs and GLUTs and will pass through the blood brain barrier
      (BBB). In vitro Me-4FDG autoradiography was used to map the distribution of
      uptake by functional SGLTs in brain slices with a comparable result from in vitro
      4-FDG autoradiography. Immunohistochemical assays showed that uptake was
      consistent with the distribution of SGLT protein. Ex vivo 4-FDG autoradiography
      showed that SGLTs in these areas are functionally active in the normal in vivo
      brain. The results establish that SGLTs are a normal part of the physiology of
      specific areas of the brain, including hippocampus, amygdala, hypothalamus, and
      cerebral cortices. 4-FDG PET imaging also established that this BBB-permeable
      SGLT tracer now offers a functional imaging approach in humans to assess
      regulation of SGLT activity in health and disease.

PMID- 20826763
TI  - Pharmacological inhibition of TRPM4 hyperpolarizes vascular smooth muscle.
AB  - The contractile state of vascular smooth muscle cells is regulated by small
      changes in membrane potential that gate voltage-dependent calcium channels. The
      melastatin transient receptor potential (TRP) channel TRPM4 is a critical
      mediator of pressure-induced membrane depolarization and arterial constriction. A
      recent study shows that the tricyclic compound 9-phenanthrol inhibits TRPM4, but
      not the related channel TRPM5. The current study investigated the specificity of
      9-phenanthrol and the effects of the compound on pressure-induced smooth muscle
      depolarization and arterial constriction. Patch-clamp electrophysiology revealed
      that 9-phenanthrol blocks native TRPM4 currents in freshly isolated smooth muscle
      cells in a concentration-dependent manner (IC(50) = 10.6 MUM). 9-Phenanthrol (30
      MUM) had no effect on maximum evoked currents in human embryonic kidney cells
      expressing recombinant TRPC3 or TRPC6 channels. Large-conductance Ca(2+)
      activated K(+), voltage-dependent K(+), inwardly rectifying K(+), and voltage
      dependent Ca(2+) channel activity in native cerebral artery myocytes was not
      altered by administration of 9-phenanthrol (30 MUM). Using intracellular
      microelectrodes to record smooth muscle membrane potential in isolated cerebral
      arteries pressurized to 70 mmHg, we found that 9-phenanthrol (30 MUM) reversibly
      hyperpolarized the membrane from ~-40 mV to ~-70 mV. In addition, we found that
      myogenic tone was reversibly abolished when vessels were exposed to 9
      phenanthrol. These data demonstrate that 9-phenanthrol is useful for studying the
      functional significance of TRPM4 in vascular smooth muscle cells and that TRPM4
      is an important regulator of smooth muscle cell membrane depolarization and
      arterial constriction in response to intraluminal pressure.

PMID- 20826765
TI  - The Harvard Fatigue Laboratory: contributions to World War II.
AB  - The war contributions of the Harvard Fatigue Laboratory in Cambridge, MA, were
      recorded in 169 Technical Reports, most of which were sent to the Office of the
      Quartermaster General. Earlier reports were sent to the National Research Council
      and the Office of Scientific Research and Development. Many of the reports from
      1941 and later dealt with either physical fitness of soldiers or the energetic
      cost of military tasks in extreme heat and cold. New military emergency rations
      to be manufactured in large quantities were analyzed in the Fatigue Laboratory
      and then tested in the field. Newly designed cold weather clothing was tested in
      the cold chamber at -40 degrees F, and desired improvements were made and tested
      in the field by staff and soldiers in tents and sleeping bags. Electrically
      heated clothing was designed for high-altitude flight crews and tested both in
      laboratory chambers and field tests before being issued. This eye witness account
      of the Harvard Fatigue Laboratory during World War II was recorded by Dr. G.
      Edgar Folk, who is likely the sole surviving member of that famous laboratory.

PMID- 20826764
TI  - Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell
      carcinoma.
AB  - Ovarian clear cell carcinoma (OCCC) is an aggressive human cancer that is
      generally resistant to therapy. To explore the genetic origin of OCCC, we
      determined the exomic sequences of eight tumors after immunoaffinity purification
      of cancer cells. Through comparative analyses of normal cells from the same
      patients, we identified four genes that were mutated in at least two tumors.
      PIK3CA, which encodes a subunit of phosphatidylinositol-3 kinase, and KRAS, which
      encodes a well-known oncoprotein, had previously been implicated in OCCC. The
      other two mutated genes were previously unknown to be involved in OCCC: PPP2R1A
      encodes a regulatory subunit of serine/threonine phosphatase 2, and ARID1A
      encodes adenine-thymine (AT)-rich interactive domain-containing protein 1A, which
      participates in chromatin remodeling. The nature and pattern of the mutations
      suggest that PPP2R1A functions as an oncogene and ARID1A as a tumor-suppressor
      gene. In a total of 42 OCCCs, 7% had mutations in PPP2R1A and 57% had mutations
      in ARID1A. These results suggest that aberrant chromatin remodeling contributes
      to the pathogenesis of OCCC.

PMID- 20826766
TI  - When t-tests or Wilcoxon-Mann-Whitney tests won't do.
AB  - t-Tests are widely used by researchers to compare the average values of a numeric
      outcome between two groups. If there are doubts about the suitability of the data
      for the requirements of a t-test, most notably the distribution being non-normal,
      the Wilcoxon-Mann-Whitney test may be used instead. However, although often
      applied, both tests may be invalid when discrete and/or extremely skew data are
      analyzed. In medicine, extremely skewed data having an excess of zeroes are often
      observed, representing a numeric outcome that does not occur for a large
      percentage of cases (so is often zero) but which also sometimes takes relatively
      large values. For data such as this, application of the t-test or Wilcoxon-Mann
      Whitney test could lead researchers to draw incorrect conclusions. A valid
      alternative is regression modeling to quantify the characteristics of the data.
      The increased availability of software has simplified the application of these
      more complex statistical analyses and hence facilitates researchers to use them.
      In this article, we illustrate the methodology applied to a comparison of cyst
      counts taken from control and steroid-treated fetal mouse kidneys.

PMID- 20826767
TI  - Effect of self-assessment on test scores: student perceptions.
AB  - After a sudden increase in most of the individual grades in a multiple-choice
      test, students were asked to rank the three most relevant factors responsible for
      this outcome. Among eight others, the availability of a test for self-assessment
      before the final test was by far the most frequently mentioned (82.4% of the
      students). Questions applied during different course activities did not have the
      same effect on student scores as the "online" self-assessment test.

PMID- 20826768
TI  - Teaching undergraduates the process of peer review: learning by doing.
AB  - An active approach allowed undergraduates in Health Sciences to learn the
      dynamics of peer review at first hand. A four-stage process was used. In stage 1,
      students formed self-selected groups to explore specific issues. In stage 2, each
      group posted their interim reports online on a specific date. Each student read
      all the other reports and prepared detailed critiques. In stage 3, each report
      was discussed at sessions where the lead discussant was selected at random. All
      students participated in the peer review process. The written critiques were
      collated and returned to each group, who were asked to resubmit their revised
      reports within 2 wk. In stage 4, final submissions accompanied by rebuttals were
      graded. Student responses to a questionnaire were highly positive. They
      recognized the individual steps in the standard peer review, appreciated the
      complexities involved, and got a first-hand experience of some of the inherent
      variabilities involved. The absence of formal presentations and the opportunity
      to read each other's reports permitted them to study issues in greater depth.

PMID- 20826769
TI  - Student perceptions regarding the usefulness of explicit discussion of "Structure
      of the Observed Learning Outcome" taxonomy.
AB  - One method of grading responses of the descriptive type is by using Structure of
      Observed Learning Outcomes (SOLO) taxonomy. The basis of this study was the
      expectation that if students were oriented to SOLO taxonomy, it would provide
      them an opportunity to understand some of the factors that teachers consider
      while grading descriptive responses and possibly develop strategies to improve
      scores. We first sampled the perceptions of 68 second-year undergraduate medical
      students doing the Respiratory System course regarding the usefulness of explicit
      discussion of SOLO taxonomy. Subsequently, in a distinct cohort of 20 second-year
      medical students doing the Central Nervous System course, we sought to determine
      whether explicit illustration of SOLO taxonomy combined with some advice on
      better answering descriptive test questions (to an experimental group) resulted
      in better student scores in a continuous assessment test compared with providing
      advice for better answering test questions but without any reference to SOLO
      taxonomy (the control group). Student ratings of the clarity of the presentation
      on SOLO taxonomy appeared satisfactory to the authors, as was student
      understanding of our presentation. The majority of participants indicated that
      knowledge of SOLO taxonomy would help them study and prepare better answers for
      questions of the descriptive type. Although scores in the experimental and
      control group were comparable, this experience nonetheless provided us with the
      motivation to orient students to SOLO taxonomy early on in the medical program
      and further research factors that affect students' development of strategies
      based on knowledge of SOLO taxonomy.

PMID- 20826770
TI  - Process-oriented guided-inquiry learning in an introductory anatomy and
      physiology course with a diverse student population.
AB  - Process-oriented guided-inquiry learning (POGIL), a pedagogical technique
      initially developed for college chemistry courses, has been implemented for 2 yr
      in a freshman-level anatomy and physiology course at a small private college. The
      course is populated with students with backgrounds ranging from no previous
      college-level science to junior and senior biology, biochemistry, and forensic
      science majors. Fifty percent of the lectures in the course were replaced with
      POGIL activities, performed in class by students working collaboratively in small
      groups. The introduction of POGIL pedagogy into the second half of a two-semester
      anatomy and physiology course significantly improved student performance on
      summative evaluations. Overall course scores increased from a mean score of 76%
      to 89% in the three semesters after POGIL was introduced. Performance on the same
      multiple-choice final exam rose from a mean of 68% to 88% over the same time
      period. Most significantly, the rate of students earning a D or F in the course
      was halved in the first two semesters after POGIL was introduced and was 0% in
      the third semester. Student satisfaction with the method was high, and most
      students perceived the value of this form of instruction.

PMID- 20826771
TI  - Teaching diffusion with a coin.

PMID- 20826772
TI  - Modeling a neural network as a teaching tool for the learning of the structure
      function relationship.

PMID- 20826773
TI  - The colon is a digestive organ!

PMID- 20826774
TI  - FMN binding and photochemical properties of plant putative photoreceptors
      containing two LOV domains, LOV/LOV proteins.
AB  - LOV domains function as blue light-sensing modules in various photoreceptors in
      plants, fungi, algae, and bacteria. A LOV/LOV protein (LLP) has been found from
      Arabidopsis thaliana (AtLLP) as a two LOV domain-containing protein. However, its
      function remains unknown. We isolated cDNA clones coding for an LLP homolog from
      tomato (Solanum lycopersicum) and two homologs from the moss Physcomitrella
      patens. The tomato LLP (SlLLP) contains two LOV domains (LOV1 and LOV2 domains),
      as in AtLLP. Most of the amino acids required for association with chromophore
      are conserved in both LOV domains, except that the amino acid at the position
      equivalent to the cysteine essential for cysteinyl adduct formation is glycine in
      the LOV1 domain as in AtLLP. When expressed in Escherichia coli, SlLLP binds FMN
      and undergoes a self-contained photocycle upon irradiation of blue light.
      Analyses using mutant SlLLPs revealed that SlLLP binds FMN in both LOV domains,
      although the LOV1 domain does not show spectral changes on irradiation. However,
      when Gly(66) in the LOV1 domain, which is located at the position equivalent to
      the essential cysteine of LOV domains, is replaced by cysteine, the mutated LOV1
      domain shows light-induced spectral changes. In addition, all four LOV domains of
      P. patens LLPs (PpLLP1 and PpLLP2) show the typical features of LOV domains,
      including the reactive cysteine in each. This study shows that plants have a new
      LOV domain-containing protein family with the typical biochemical and
      photochemical properties of other LOV domain-containing proteins such as the
      phototropins.

PMID- 20826775
TI  - Tocopherol transfer protein sensitizes prostate cancer cells to vitamin E.
AB  - Prostate cancer is a major cause of mortality in men in developed countries. It
      has been reported that the naturally occurring antioxidant alpha-tocopherol
      (vitamin E) attenuates prostate cancer cell proliferation in cultured cells and
      mouse models. We hypothesized that overexpression of the tocopherol transfer
      protein (TTP), a vitamin E-binding protein that regulates tocopherol status, will
      sensitize prostate cancer cells to the anti-proliferative actions of the vitamin.
      To test this notion, we manipulated the expression levels of TTP in cultured
      prostate cells (LNCaP, PC3, DU145, and RWPE-1) using overexpression and knockdown
      approaches. Treatment of cells with tocopherol caused a time- and dose-dependent
      inhibition of cell proliferation. Overexpression of TTP dramatically sensitized
      the cells to the apoptotic effects of alpha-tocopherol, whereas reduction
      ("knockdown") of TTP expression resulted in resistance to the vitamin. TTP levels
      also augmented the inhibitory effects of vitamin E on proliferation in semi-solid
      medium. The sensitizing effects of TTP were paralleled by changes in the
      intracellular accumulation of a fluorescent analog of vitamin E and by a
      reduction in intracellular levels of reactive oxygen species and were not
      observed when a naturally occurring, ligand binding-defective mutant of TTP was
      used. We conclude that TTP sensitizes prostate cancer cells to the anti
      proliferative effects of vitamin E and that this activity stems from the ability
      of protein to increase the intracellular accumulation of the antioxidant. These
      observations support the notion that individual changes in the expression level
      or activity of TTP may determine the responsiveness of prostate cancer patients
      to intervention strategies that utilize vitamin E.

PMID- 20826776
TI  - Stress effects on FosB- and interleukin-8 (IL8)-driven ovarian cancer growth and
      metastasis.
AB  - A growing number of studies indicate that chronic stress can accelerate tumor
      growth due to sustained sympathetic nervous system activation. Our recent
      findings suggest that chronic stress is associated with increased IL8 levels.
      Here, we examined the molecular and biological significance of IL8 in stress
      induced tumor growth. Norepinephrine (NE) treatment of ovarian cancer cells
      resulted in a 250-300% increase in IL8 protein and 240-320% increase in its mRNA
      levels. Epinephrine treatment resulted in similar increases. Moreover, NE
      treatment resulted in a 3.5-4-fold increase in IL8 promoter activity. These
      effects were blocked by propranolol. Promoter deletion analyses suggested that
      AP1 transcription factors might mediate catecholamine-stimulated up-regulation of
      IL8. siRNA inhibition studies identified FosB as the pivotal component
      responsible for IL8 regulation by NE. In vivo chronic stress resulted in
      increased tumor growth (by 221 and 235%; p < 0.01) in orthotopic xenograft models
      involving SKOV3ip1 and HeyA8 ovarian carcinoma cells. This enhanced tumor growth
      was completely blocked by IL8 or FosB gene silencing using 1,2-dioleoyl-sn
      glycero-3-phosphatidylcholine nanoliposomes. IL8 and FosB silencing reduced
      microvessel density (based on CD31 staining) by 2.5- and 3.5-fold, respectively
      (p < 0.001). Our findings indicate that neurobehavioral stress leads to FosB
      driven increases in IL8, which is associated with increased tumor growth and
      metastases. These findings may have implications for ovarian cancer management.

PMID- 20826777
TI  - The v-myc-induced Q83 lipocalin is a siderocalin.
AB  - Siderocalins are atypical lipocalins able to capture siderophores with high
      affinity. They contribute to the innate immune response by interfering with
      bacterial siderophore-mediated iron uptake but are also involved in numerous
      physiological processes such as inflammation, iron delivery, tissue
      differentiation, and cancer progression. The Q83 lipocalin was originally
      identified based on its overexpression in quail embryo fibroblasts transformed by
      the v-myc oncogene. We show here that Q83 is a siderocalin, binding the
      siderophore enterobactin with an affinity and mode of binding nearly identical to
      that of neutrophil gelatinase-associated lipocalin (NGAL), the prototypical
      siderocalin. This strengthens the role of siderocalins in cancer progression and
      inflammation. In addition, we also present the solution structure of Q83 in
      complex with intact enterobactin and a detailed analysis of the Q83 binding mode,
      including mutagenesis of the critical residues involved in enterobactin binding.
      These data provide a first insight into the molecular details of siderophore
      binding and delineate the common molecular properties defining the siderocalin
      protein family.

PMID- 20826778
TI  - Structural basis of E2-25K/UBB+1 interaction leading to proteasome inhibition and
      neurotoxicity.
AB  - E2-25K/Hip2 is an unusual ubiquitin-conjugating enzyme that interacts with the
      frameshift mutant of ubiquitin B (UBB(+1)) and has been identified as a crucial
      factor regulating amyloid-beta neurotoxicity. To study the structural basis of
      the neurotoxicity mediated by the E2-25K-UBB(+1) interaction, we determined the
      three-dimensional structures of UBB(+1), E2-25K and the E2-25K/ubiquitin, and E2
      25K/UBB(+1) complex. The structures revealed that ubiquitin or UBB(+1) is bound
      to E2-25K via the enzyme MGF motif and residues in alpha9 of the enzyme.
      Polyubiquitylation assays together with analyses of various E2-25K mutants showed
      that disrupting UBB(+1) binding markedly diminishes synthesis of neurotoxic
      UBB(+1)-anchored polyubiquitin. These results suggest that the interaction
      between E2-25K and UBB(+1) is critical for the synthesis and accumulation of
      UBB(+1)-anchored polyubiquitin, which results in proteasomal inhibition and
      neuronal cell death.

PMID- 20826779
TI  - Heterogeneity of phosphatidic acid levels and distribution at the plasma membrane
      in living cells as visualized by a Foster resonance energy transfer (FRET)
      biosensor.
AB  - Phosphatidic acid (PA) is one of the major phospholipids in the plasma membrane.
      Although it has been reported that PA plays key roles in cell survival and
      morphology, it remains unknown when and where PA is produced in the living cell.
      Based on the principle of Forster resonance energy transfer (FRET), we generated
      PA biosensor, and named Pii (phosphatidic acid indicator). In these biosensors,
      the lipid-binding domain of DOCK2 is sandwiched with the cyan fluorescent protein
      and yellow fluorescent protein and is tagged with the plasma membrane-targeting
      sequence of K-Ras. The addition of synthetic PA, or the activation of
      phospholipase D or diacylglycerol kinase at the plasma membrane, changed the
      level of FRET in Pii-expressing cells, demonstrating the response of Pii to PA.
      The biosensor also detected divergent PA content among various cell lines as well
      as within one cell line. Interestingly, the growth factor-induced increment in PA
      content correlated negatively with the basal PA content before stimulation,
      suggesting the presence of an upper threshold in the PA concentration at the
      plasma membrane. The biosensor also revealed uneven PA distribution within the
      cell, i.e. the basal level and growth factor-induced accumulation of PA was
      higher at the cell-free edges than at the cell-cell contact region. An
      insufficient increase in PA may account for ineffective Ras activation at areas
      of cell-cell contact. In conclusion, the PA biosensor Pii is a versatile tool for
      examining heterogeneity in the content and distribution of PA in single cells as
      well as among different cells.

PMID- 20826780
TI  - Factor X/Xa elicits protective signaling responses in endothelial cells directly
      via PAR-2 and indirectly via endothelial protein C receptor-dependent recruitment
      of PAR-1.
AB  - We recently demonstrated that the Gla domain-dependent interaction of protein C
      with endothelial protein C receptor (EPCR) leads to dissociation of the receptor
      from caveolin-1 and recruitment of PAR-1 to a protective signaling pathway. Thus,
      the activation of PAR-1 by either thrombin or PAR-1 agonist peptide elicited a
      barrier-protective response if endothelial cells were preincubated with protein
      C. In this study, we examined whether other vitamin K-dependent coagulation
      protease zymogens can modulate PAR-dependent signaling responses in endothelial
      cells. We discovered that the activation of both PAR-1 and PAR-2 in endothelial
      cells pretreated with factor FX (FX)-S195A, but not other procoagulant protease
      zymogens, also results in initiation of protective intracellular responses.
      Interestingly, similar to protein C, FX interaction with endothelial cells leads
      to dissociation of EPCR from caveolin-1 and recruitment of PAR-1 to a protective
      pathway. Further studies revealed that, FX activated by factor VIIa on tissue
      factor bearing endothelial cells also initiates protective signaling responses
      through the activation of PAR-2 independent of EPCR mobilization. All results
      could be recapitulated by the receptor agonist peptides to both PAR-1 and PAR-2.
      These results suggest that a cross-talk between EPCR and an unknown FX/FXa
      receptor, which does not require interaction with the Gla domain of FX, recruits
      PAR-1 to protective signaling pathways in endothelial cells.

PMID- 20826781
TI  - Calmodulin regulates Ca2+-sensing receptor-mediated Ca2+ signaling and its cell
      surface expression.
AB  - The Ca(2+)-sensing receptor (CaSR) is a member of family C of the GPCRs
      responsible for sensing extracellular Ca(2+) ([Ca(2+)](o)) levels, maintaining
      extracellular Ca(2+) homeostasis, and transducing Ca(2+) signaling from the
      extracellular milieu to the intracellular environment. In the present study, we
      have demonstrated a Ca(2+)-dependent, stoichiometric interaction between CaM and
      a CaM-binding domain (CaMBD) located within the C terminus of CaSR (residues 871
      898). Our studies suggest a wrapping around 1-14-like mode of interaction that
      involves global conformational changes in both lobes of CaM with concomitant
      formation of a helical structure in the CaMBD. More importantly, the Ca(2+)
      dependent association between CaM and the C terminus of CaSR is critical for
      maintaining proper responsiveness of intracellular Ca(2+) responses to changes in
      extracellular Ca(2+) and regulating cell surface expression of the receptor.

PMID- 20826782
TI  - The novel PMCA2 pump mutation Tommy impairs cytosolic calcium clearance in hair
      cells and links to deafness in mice.
AB  - The mechanotransduction process in hair cells in the inner ear is associated with
      the influx of calcium from the endolymph. Calcium is exported back to the
      endolymph via the splice variant w/a of the PMCA2 of the stereocilia membrane. To
      further investigate the role of the pump, we have identified and characterized a
      novel ENU-induced mouse mutation, Tommy, in the PMCA2 gene. The mutation causes a
      non-conservative E629K change in the second intracellular loop of the pump that
      harbors the active site. Tommy mice show profound hearing impairment from P18,
      with significant differences in hearing thresholds between wild type and
      heterozygotes. Expression of mutant PMCA2 in CHO cells shows calcium extrusion
      impairment; specifically, the long term, non-stimulated calcium extrusion
      activity of the pump is inhibited. Calcium extrusion was investigated directly in
      neonatal organotypic cultures of the utricle sensory epithelium in Tommy mice.
      Confocal imaging combined with flash photolysis of caged calcium showed
      impairment of calcium export in both Tommy heterozygotes and homozygotes.
      Immunofluorescence studies of the organ of Corti in homozygous Tommy mice showed
      a progressive base to apex degeneration of hair cells after P40. Our results on
      the Tommy mutation along with previously observed interactions between cadherin
      23 and PMCA2 mutations in mouse and humans underline the importance of
      maintaining the appropriate calcium concentrations in the endolymph to control
      the rigidity of cadherin and ensure the function of interstereocilia links,
      including tip links, of the stereocilia bundle.

PMID- 20826783
TI  - Tgfbeta signaling directly induces Arf promoter remodeling by a mechanism
      involving Smads 2/3 and p38 MAPK.
AB  - We have investigated how the Arf gene product, p19(Arf), is activated by Tgfbeta
      during mouse embryo development to better understand how this important tumor
      suppressor is controlled. Taking advantage of new mouse models, we provide
      genetic evidence that Arf lies downstream of Tgfbeta signaling in cells arising
      from the Wnt1-expressing neural crest and that the anti-proliferative effects of
      Tgfbeta depend on Arf in vivo. Tgfbeta1, -2, and -3 (but not BMP-2, another
      member of the Tgfbeta superfamily) induce p19(Arf) expression in wild type mouse
      embryo fibroblasts (MEFs), and they enhance Arf promoter activity in
      Arf(lacZ/lacZ) MEFs. Application of chemical inhibitors of Smad-dependent and 
      independent pathways show that SB431542, a Tgfbeta type I receptor (TbetarI)
      inhibitor, and SB203580, a p38 MAPK inhibitor, impede Tgfbeta2 induction of Arf.
      Genetic studies confirm the findings; transient knockdown of Smad2, Smad3, or p38
      MAPK blunt Tgfbeta2 effects, as does Cre recombinase treatment of Tgfbr2(fl/fl)
      MEFs to delete Tgfbeta receptor II. Chromatin immunoprecipitation reveals that
      Tgfbeta rapidly induces Smads 2/3 binding and histone H3 acetylation at genomic
      DNA proximal to Arf exon 1beta. This is followed by increased RNA polymerase II
      binding and progressively increased Arf primary and mature transcripts from 24
      through 72 h, indicating that increased transcription contributes to p19(Arf)
      increase. Last, Arf induction by oncogenic Ras depends on p38 MAPK but is
      independent of TbetarI activation of Smad 2. These findings add to our
      understanding of how developmental and tumorigenic signals control Arf expression
      in vivo and in cultured MEFs.

PMID- 20826784
TI  - Acetylation directs survivin nuclear localization to repress STAT3 oncogenic
      activity.
AB  - The multiple functions of the oncofetal protein survivin are dependent on its
      selective expression patterns within immunochemically distinct subcellular pools.
      The mechanism by which survivin localizes to these compartments, however, is only
      partly understood. Here we show that nuclear accumulation of survivin is promoted
      by CREB-binding protein (CBP)-dependent acetylation on lysine 129 (129K, Lys
      129). We demonstrate a mechanism by which survivin acetylation at this position
      results in its homodimerization, while deacetylation promotes the formation of
      survivin monomers that heterodimerize with CRM1 and facilitate its nuclear
      export. Using proteomic analysis, we identified the oncogenic transcription
      factor STAT3 as a binding partner of nuclear survivin. We show that acetylated
      survivin binds to the N-terminal transcriptional activation domain of the STAT3
      dimer and represses STAT3 transactivation of target gene promoters. Using
      multiplex PCR and DNA sequencing, we identified a single-nucleotide polymorphism
      (A -> G) at Lys-129 that exists as a homozygous mutation in a neuroblastoma cell
      line and corresponds with a defect in survivin nuclear localization. Our results
      demonstrate that the dynamic equilibrium between survivin acetylation and
      deacetylation at amino acid 129 determines its interaction with CRM1, its
      subsequent subcellular localization, and its ability to inhibit STAT3
      transactivation, providing a potential route for therapeutic intervention in
      STAT3-dependent tumors.

PMID- 20826785
TI  - Stable interaction between the human proliferating cell nuclear antigen loader
      complex Ctf18-replication factor C (RFC) and DNA polymerase {epsilon} is mediated
      by the cohesion-specific subunits, Ctf18, Dcc1, and Ctf8.
AB  - One of the proliferating cell nuclear antigen loader complexes, Ctf18-replication
      factor C (RFC), is involved in sister chromatid cohesion. To examine its
      relationship with factors involved in DNA replication, we performed a proteomics
      analysis of Ctf18-interacting proteins. We found that Ctf18 interacts with a
      replicative DNA polymerase, DNA polymerase epsilon (pol epsilon). Co
      immunoprecipitation with recombinant Ctf18-RFC and pol epsilon demonstrated that
      their binding is direct and mediated by two distinct interactions, one weak and
      one stable. Three subunits that are specifically required for cohesion in yeast,
      Ctf18, Dcc1, and Ctf8, formed a trimeric complex (18-1-8) and together enabled
      stable binding with pol epsilon. The C-terminal 23-amino acid stretch of Ctf18
      was necessary for the trimeric association of 18-1-8 and was required for the
      stable interaction. The weak interaction was observed with alternative loader
      complexes including Ctf18-RFC(5), which lacks Dcc1 and Ctf8, suggesting that the
      common loader structures, including the RFC small subunits (RFC2-5), are
      responsible for the weak interaction. The two interaction modes, mediated through
      distinguishable structures of Ctf18-RFC, both occurred through the N-terminal
      half of pol epsilon, which includes the catalytic domain. The addition of Ctf18
      RFC or Ctf18-RFC(5) to the DNA synthesis reaction caused partial inhibition and
      stimulation, respectively. Thus, Ctf18-RFC has multiple interactions with pol
      epsilon that promote polymorphic modulation of DNA synthesis. We propose that
      their interaction alters the DNA synthesis mode to enable the replication fork to
      cooperate with the establishment of cohesion.

PMID- 20826787
TI  - Enhanced anti-tumor activity by the combination of the natural compounds (-)
      epigallocatechin-3-gallate and luteolin: potential role of p53.
AB  - Natural dietary agents have drawn a great deal of attention toward cancer
      prevention because of their wide safety margin. However, single agent
      intervention has failed to bring the expected outcome in clinical trials;
      therefore, combinations of chemopreventive agents are gaining increasingly
      popularity. In the present study, we investigated a combinatorial approach using
      two natural dietary polyphenols, luteolin and EGCG, and found that their
      combination at low doses (at which single agents induce minimal apoptosis)
      synergistically increased apoptosis (3-5-fold more than the additive level of
      apoptosis) in both head and neck and lung cancer cell lines. This combination
      also significantly inhibited growth of xenografted tumors in nude mice. The in
      vivo findings also were supported by significant inhibition of Ki-67 expression
      and increase in TUNEL-positive cells in xenografted tissues. Mechanistic studies
      revealed that the combination induced mitochondria-dependent apoptosis in some
      cell lines and mitochondria-independent apoptosis in others. Moreover, we found
      more efficient stabilization and ATM-dependent Ser(15) phosphorylation of p53 due
      to DNA damage by the combination, and ablation of p53 using shRNA strongly
      inhibited apoptosis as evidenced by decreased poly(ADP-ribose) polymerase and
      caspase-3 cleavage. In addition, we observed mitochondrial translocation of p53
      after treatment with luteolin or the combination of EGCG and luteolin. Taken
      together, our results for the first time suggest that the combination of luteolin
      and EGCG has synergistic/additive growth inhibitory effects and provides an
      important rationale for future chemoprevention trials of head and neck and lung
      cancers.

PMID- 20826786
TI  - Structural and mechanistic studies on Klebsiella pneumoniae 2-Oxo-4-hydroxy-4
      carboxy-5-ureidoimidazoline decarboxylase.
AB  - The stereospecific oxidative degradation of uric acid to (S)-allantoin was
      recently shown to proceed via three enzymatic steps. The final conversion is a
      decarboxylation of the unstable intermediate 2-oxo-4-hydroxy-4-carboxy-5
      ureidoimidazoline (OHCU) and is catalyzed by OHCU decarboxylase. Here we present
      the structures of Klebsiella pneumoniae OHCU decarboxylase in unliganded form and
      with bound allantoin. These structures provide evidence that ligand binding
      organizes the active site residues for catalysis. Modeling of the substrate and
      intermediates provides additional support for this hypothesis. In addition we
      characterize the steady state kinetics of this enzyme and report the first OHCU
      decarboxylase inhibitor, allopurinol, a structural isomer of hypoxanthine. This
      molecule is a competitive inhibitor of K. pneumoniae OHCU decarboxylase with a
      K(i) of 30 +/- 2 MUM. Circular dichroism measurements confirm structural
      observations that this inhibitor disrupts the necessary organization of the
      active site. Our structural and biochemical studies also provide further insights
      into the mechanism of catalysis of OHCU decarboxylation.

PMID- 20826788
TI  - Shallow boomerang-shaped influenza hemagglutinin G13A mutant structure promotes
      leaky membrane fusion.
AB  - Our previous studies showed that an angled boomerang-shaped structure of the
      influenza hemagglutinin (HA) fusion domain is critical for virus entry into host
      cells by membrane fusion. Because the acute angle of ~105 degrees  of the wild
      type fusion domain promotes efficient non-leaky membrane fusion, we asked whether
      different angles would still support fusion and thus facilitate virus entry.
      Here, we show that the G13A fusion domain mutant produces a new leaky fusion
      phenotype. The mutant fusion domain structure was solved by NMR spectroscopy in a
      lipid environment at fusion pH. The mutant adopted a boomerang structure similar
      to that of wild type but with a shallower kink angle of ~150 degrees . G13A
      perturbed the structure of model membranes to a lesser degree than wild type but
      to a greater degree than non-fusogenic fusion domain mutants. The strength of
      G13A binding to lipid bilayers was also intermediate between that of wild type
      and non-fusogenic mutants. These membrane interactions provide a clear link
      between structure and function of influenza fusion domains: an acute angle is
      required to promote clean non-leaky fusion suitable for virus entry presumably by
      interaction of the fusion domain with the transmembrane domain deep in the lipid
      bilayer. A shallower angle perturbs the bilayer of the target membrane so that it
      becomes leaky and unable to form a clean fusion pore. Mutants with no fixed
      boomerang angle interacted with bilayers weakly and did not promote any fusion or
      membrane perturbation.

PMID- 20826789
TI  - Plasma kallikrein promotes epidermal growth factor receptor transactivation and
      signaling in vascular smooth muscle through direct activation of protease
      activated receptors.
AB  - The kallikrein-kinin system, along with the interlocking renin-angiotensin
      system, is a key regulator of vascular contractility and injury response. The
      principal effectors of the kallikrein-kinin system are plasma and tissue
      kallikreins, proteases that cleave high molecular weight kininogen to produce
      bradykinin. Most of the cellular actions of kallikrein (KK) are thought to be
      mediated by bradykinin, which acts via G protein-coupled B1 and B2 bradykinin
      receptors on VSMCs and endothelial cells. Here, we find that primary aortic
      vascular smooth muscle but not endothelial cells possess the ability to activate
      plasma prekallikrein. Surprisingly, exposing VSMCs to prekallikrein leads to
      activation of the ERK1/2 mitogen-activated protein kinase cascade via a mechanism
      that requires kallikrein activity but does not involve bradykinin receptors. In
      transfected HEK293 cells, we find that plasma kallikrein directly activates G
      protein-coupled protease-activated receptors (PARs) 1 and 2, which possess
      consensus kallikrein cleavage sites, but not PAR4. In vascular smooth muscles, KK
      stimulates ADAM (a disintegrin and metalloprotease) 17 activity via a PAR1/2
      receptor-dependent mechanism, leading sequentially to release of the endogenous
      ADAM17 substrates, amphiregulin and tumor necrosis factor-alpha, metalloprotease
      dependent transactivation of epidermal growth factor receptors, and
      metalloprotease and epidermal growth factor receptor-dependent ERK1/2 activation.
      These results suggest a novel mechanism of bradykinin-independent kallikrein
      action that may contribute to the regulation of vascular responses in
      pathophysiologic states, such as diabetes mellitus.

PMID- 20826790
TI  - Vasodilator-stimulated phosphoprotein (VASP) induces actin assembly in dendritic
      spines to promote their development and potentiate synaptic strength.
AB  - Dendritic spines are small actin-rich structures that receive the majority of
      excitatory synaptic input in the brain. The actin-based dynamics of spines are
      thought to mediate synaptic plasticity, which underlies cognitive processes, such
      as learning and memory. However, little is known about the molecular mechanisms
      that regulate actin dynamics in spines and synapses. In this study we show the
      multifunctional actin-binding protein vasodilator-stimulated phosphoprotein
      (VASP) regulates the density, size, and morphology of dendritic spines by
      inducing actin assembly in these structures. Knockdown of endogenous VASP by
      siRNA led to a significant decrease in the density of spines and synapses,
      whereas expression of siRNA-resistant VASP rescued this defect. The ability of
      VASP to modulate spine and synapse formation, maturation, and spine head
      enlargement is dependent on its actin binding Ena/VASP homology 2 (EVH2) domain
      and its EVH1 domain, which contributes to VASP localization to actin-rich
      structures. Moreover, VASP increases the amount of PSD-scaffolding proteins and
      the number of surface GluR1-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid receptors (AMPARs) in spines. VASP knockdown results in a
      reduction in surface AMPAR density, suggesting a role for this protein in
      regulating synaptic strength. Consistent with this, VASP significantly enhances
      the retention of GluR1 in spines as determined by fluorescence recovery after
      photobleaching and increases AMPAR-mediated synaptic transmission. Collectively,
      our results suggest that actin polymerization and bundling by VASP are critical
      for spine formation, expansion, and modulating synaptic strength.

PMID- 20826791
TI  - An interdomain interaction of the androgen receptor is required for its
      aggregation and toxicity in spinal and bulbar muscular atrophy.
AB  - Polyglutamine expansion within the androgen receptor (AR) causes spinal and
      bulbar muscular atrophy (SBMA) and is associated with misfolded and aggregated
      species of the mutant AR. We showed previously that nuclear localization of the
      mutant AR was necessary but not sufficient for SBMA. Here we show that an
      interdomain interaction of the AR that is central to its function within the
      nucleus is required for AR aggregation and toxicity. Ligands that prevent the
      interaction between the amino-terminal FXXLF motif and carboxyl-terminal AF-2
      domain (N/C interaction) prevented toxicity and AR aggregation in an SBMA cell
      model and rescued primary SBMA motor neurons from 5alpha-dihydrotestosterone
      induced toxicity. Moreover, genetic mutation of the FXXLF motif prevented AR
      aggregation and 5alpha-dihydrotestosterone toxicity. Finally, selective androgen
      receptor modulators, which prevent the N/C interaction, ameliorated AR
      aggregation and toxicity while maintaining AR function, highlighting a novel
      therapeutic strategy to prevent the SBMA phenotype while retaining AR
      transcriptional function.

PMID- 20826792
TI  - miR-21 and miR-31 converge on TIAM1 to regulate migration and invasion of colon
      carcinoma cells.
AB  - TGF-beta promotes cell migration and invasion, an attribute that is linked to the
      pro-metastasis function of this cytokine in late stage cancers. The LIM 1863
      colon carcinoma organoid undergoes epithelial-mesenchymal transition (EMT) in
      response to TGF-beta. This process is markedly accelerated by TNF-alpha, and we
      found that the levels of miR-21 and miR-31 were prominently elevated under the
      synergistic actions of TGF-beta/TNF-alpha. Consistent with this, overexpression
      of either miR-21 or miR-31 significantly enhanced the effect of TGF-beta alone on
      LIM 1863 morphological changes. More importantly, transwell assays demonstrated
      the positive effects of both miR-21 and miR-31 in TGF-beta regulation of LIM 1863
      motility and invasiveness. Elevated levels of miR-21 and miR-31 also enhanced
      motility and invasiveness of other colon carcinoma cell lines. We present
      compelling evidence that TIAM1, a guanidine exchange factor of the Rac GTPase, is
      a direct target of both miR-21 and miR-31. Indeed in LIM 1863 cells, suppression
      of TIAM1 is required for miR-21/miR-31 to enhance cell migration and invasion.
      Therefore, we have uncovered miR-21 and miR-31 as downstream effectors of TGF
      beta in facilitating invasion and metastasis of colon carcinoma cells.

PMID- 20826793
TI  - Intermolecular autophosphorylation regulates myosin IIIa activity and
      localization in parallel actin bundles.
AB  - Myosin IIIa (Myo3A) transports cargo to the distal end of actin protrusions and
      contains a kinase domain that is thought to autoregulate its activity. Because
      Myo3A tends to cluster at the tips of actin protrusions, we investigated whether
      intermolecular phosphorylation could regulate Myo3A biochemical activity,
      cellular localization, and cellular function. Inactivation of Myo3A 2IQ kinase
      domain with the point mutation K50R did not alter maximal ATPase activity,
      whereas phosphorylation of Myo3A 2IQ resulted in reduced maximal ATPase activity
      and actin affinity. The rate and degree of Myo3A 2IQ autophosphorylation was
      unchanged by the presence of actin but was found to be dependent upon Myo3A 2IQ
      concentration within the range of 0.1 to 1.2 MUm, indicating intermolecular
      autophosphorylation. In cultured cells, we observed that the filopodial tip
      localization of Myo3A lacking the kinase domain decreased when co-expressed with
      kinase-active, full-length Myo3A. The cellular consequence of reduced Myo3A tip
      localization was decreased filopodial density along the cell periphery,
      identifying a novel cellular function for Myo3A in mediating the formation and
      stability of actin-based protrusions. Our results suggest that Myo3A motor
      activity is regulated through a mechanism involving concentration-dependent
      autophosphorylation. We suggest that this regulatory mechanism plays an essential
      role in mediating the transport and actin bundle formation/stability functions of
      Myo3A.

PMID- 20826794
TI  - The general anesthetic propofol excites nociceptors by activating TRPV1 and TRPA1
      rather than GABAA receptors.
AB  - Anesthetic agents can induce a paradox activation and sensitization of
      nociceptive sensory neurons and, thus, potentially facilitate pain processing.
      Here we identify distinct molecular mechanisms that mediate an activation of
      sensory neurons by 2,6-diisopropylphenol (propofol), a commonly used intravenous
      anesthetic known to elicit intense pain upon injection. Clinically relevant
      concentrations of propofol activated the recombinant transient receptor potential
      (TRP) receptors TRPA1 and TRPV1 heterologously expressed in HEK293t cells. In
      dorsal root ganglion (DRG) neurons, propofol-induced activation correlated better
      to expression of TRPA1 than of TRPV1. However, pretreatment with the protein
      kinase C activator 4beta-phorbol 12-myristate 13-acetate (PMA) resulted in a
      significantly sensitized propofol-induced activation of TRPV1 in DRG neurons as
      well as in HEK293t cells. Pharmacological and genetic silencing of both TRPA1 and
      TRPV1 only partially abrogated propofol-induced responses in DRG neurons. The
      remaining propofol-induced activation was abolished by the selective gamma
      aminobutyric acid, type A (GABA(A)) receptor antagonist picrotoxin. Propofol but
      not GABA evokes a release of calcitonin gene-related peptide, a key component of
      neurogenic inflammation, from isolated peripheral nerves of wild-type but not
      TRPV1 and TRPA1-deficient mice. Moreover, propofol but not GABA induced an
      intense pain upon intracutaneous injection. As both the release of calcitonin
      gene-related peptide and injection pain by propofol seem to be independent of
      GABA(A) receptors, our data identify TRPV1 and TRPA1 as key molecules for
      propofol-induced excitation of sensory neurons. This study warrants further
      investigations into the role of anesthetics to induce nociceptor sensitization
      and to foster postoperative pain.

PMID- 20826795
TI  - Sustained glutamate receptor activation down-regulates GABAB receptors by
      shifting the balance from recycling to lysosomal degradation.
AB  - Metabotropic GABA(B) receptors are abundantly expressed at glutamatergic synapses
      where they control excitability of the synapse. Here, we tested the hypothesis
      that glutamatergic neurotransmission may regulate GABA(B) receptors. We found
      that application of glutamate to cultured cortical neurons led to rapid down
      regulation of GABA(B) receptors via lysosomal degradation. This effect was
      mimicked by selective activation of AMPA receptors and further accelerated by
      coactivation of group I metabotropic glutamate receptors. Inhibition of NMDA
      receptors, blockade of L-type Ca(2+) channels, and removal of extracellular
      Ca(2+) prevented glutamate-induced down-regulation of GABA(B) receptors,
      indicating that Ca(2+) influx plays a critical role. We further established that
      glutamate-induced down-regulation depends on the internalization of GABA(B)
      receptors. Glutamate did not affect the rate of GABA(B) receptor endocytosis but
      led to reduced recycling of the receptors back to the plasma membrane. Blockade
      of lysosomal activity rescued receptor recycling, indicating that glutamate
      redirects GABA(B) receptors from the recycling to the degradation pathway. In
      conclusion, the data indicate that sustained activation of AMPA receptors down
      regulates GABA(B) receptors by sorting endocytosed GABA(B) receptors
      preferentially to lysosomes for degradation on the expense of recycling. This
      mechanism may relieve glutamatergic synapses from GABA(B) receptor-mediated
      inhibition resulting in increased synaptic excitability.

PMID- 20826796
TI  - eNOS-beta-actin interaction contributes to increased peroxynitrite formation
      during hyperoxia in pulmonary artery endothelial cells and mouse lungs.
AB  - Oxygen toxicity is the most severe side effect of oxygen therapy in neonates and
      adults. Pulmonary damage of oxygen toxicity is related to the overproduction of
      reactive oxygen species (ROS). In the present study, we investigated the effect
      of hyperoxia on the production of peroxynitrite in pulmonary artery endothelial
      cells (PAEC) and mouse lungs. Incubation of PAEC under hyperoxia (95% O(2)) for
      24 h resulted in an increase in peroxynitrite formation. Uric acid, a
      peroxynitrite scavenger, prevented hyperoxia-induced increase in peroxynitrite.
      The increase in peroxynitrite formation is accompanied by increases in nitric
      oxide (NO) release and endothelial NO synthase (eNOS) activity. We have
      previously reported that association of eNOS with beta-actin increases eNOS
      activity and NO production in lung endothelial cells. To study whether eNOS-beta
      actin association contributes to increased peroxynitrite production, eNOS-beta
      actin interaction were inhibited by reducing beta-actin availability or by using
      a synthetic peptide (P326TAT) containing a sequence corresponding to the actin
      binding site on eNOS. We found that disruption of eNOS-beta-actin interaction
      prevented hyperoxia-induced increases in eNOS-beta-actin association, eNOS
      activity, NO and peroxynitrite production, and protein tyrosine nitration.
      Hyperoxia failed to induce the increases in eNOS activity, NO and peroxynitrite
      formation in COS-7 cells transfected with plasmids containing eNOS mutant cDNA in
      which amino acids leucine and tryptophan were replaced with alanine in the actin
      binding site on eNOS. Exposure of mice to hyperoxia resulted in significant
      increases in eNOS-beta-actin association, eNOS activity, and protein tyrosine
      nitration in the lungs. Our data indicate that increased association of eNOS with
      beta-actin in PAEC contributes to hyperoxia-induced increase in the production of
      peroxynitrite which may cause nitrosative stress in pulmonary vasculature.

PMID- 20826797
TI  - The membrane subunit NuoL(ND5) is involved in the indirect proton pumping
      mechanism of Escherichia coli complex I.
AB  - Complex I pumps protons across the membrane by using downhill redox energy. Here,
      to investigate the proton pumping mechanism by complex I, we focused on the
      largest transmembrane subunit NuoL (Escherichia coli ND5 homolog). NuoL/ND5 is
      believed to have H(+) translocation site(s), because of a high sequence
      similarity to multi-subunit Na(+)/H(+) antiporters. We mutated thirteen highly
      conserved residues between NuoL/ND5 and MrpA of Na(+)/H(+) antiporters in the
      chromosomal nuoL gene. The dNADH oxidase activities in mutant membranes were
      mostly at the control level or modestly reduced, except mutants of Glu-144, Lys
      229, and Lys-399. In contrast, the peripheral dNADH-K(3)Fe(CN)(6) reductase
      activities basically remained unchanged in all the NuoL mutants, suggesting that
      the peripheral arm of complex I was not affected by point mutations in NuoL. The
      proton pumping efficiency (the ratio of H(+)/e(-)), however, was decreased in
      most NuoL mutants by 30-50%, while the IC(50) values for asimicin (a potent
      complex I inhibitor) remained unchanged. This suggests that the H(+)/e(-)
      stoichiometry has changed from 4H(+)/2e(-) to 3H(+) or 2H(+)/2e(-) without
      affecting the direct coupling site. Furthermore, 50 MUm of 5-(N-ethyl-N
      isopropyl)-amiloride (EIPA), a specific inhibitor for Na(+)/H(+) antiporters,
      caused a 38 +/- 5% decrease in the initial H(+) pump activity in the wild type,
      while no change was observed in D178N, D303A, and D400A mutants where the H(+)
      pumping efficiency had already been significantly decreased. The electron
      transfer activities were basically unaffected by EIPA in both control and
      mutants. Taken together, our data strongly indicate that the NuoL subunit is
      involved in the indirect coupling mechanism.

PMID- 20826798
TI  - Novel isonitrile hydratase involved in isonitrile metabolism.
AB  - We previously discovered N-substituted formamide deformylase (NfdA) in
      Arthrobacter pascens F164, which degrades N-substituted formamide (Fukatsu, H.,
      Hashimoto, Y., Goda, M., Higashibata, H., and Kobayashi, M. (2004) Proc. Natl.
      Acad. Sci. U.S.A. 101, 13726-13731). In this study, we found an enzyme involved
      in the first step of isonitrile metabolism, isonitrile hydratase, that hydrates
      isonitrile to the corresponding N-substituted formamide. First, we investigated
      the optimum culture conditions for the production of isonitrile hydratase. The
      highest enzyme activity was obtained when A. pascens F164 was cultured in a
      nutrient medium containing N-benzylformamide. This Arthrobacter isonitrile
      hydratase was purified, characterized, and compared with Pseudomonas putida N19-2
      isonitrile hydratase (InhA), which is the sole one reported at present.
      Arthrobacter isonitrile hydratase was found to have a molecular mass of about 530
      kDa and to consist of 12 identical subunits. The apparent K(m) value for
      cyclohexyl isocyanide was 0.95 +/- 0.05 mm. A. pascens F164 grew and exhibited
      the isonitrile hydratase and N-substituted formamide deformylase activities when
      cultured in a medium containing an isonitrile as the sole carbon and nitrogen
      sources. However, both enzyme activities were not observed on culture in a medium
      containing glycerol and (NH(4))(2)SO(4) as the sole carbon and nitrogen sources,
      respectively. These findings suggested that the Arthrobacter enzyme is an
      inducible enzyme, possibly involved in assimilation and/or detoxification of
      isonitrile. Moreover, gene cloning of the Arthrobacter enzyme revealed no
      sequence similarity between this enzyme and InhA. Comparison of their properties
      and features demonstrated that the two enzymes are biochemically,
      immunologically, and structurally different from each other. Thus, we discovered
      a new isonitrile hydratase named InhB.

PMID- 20826799
TI  - Malaria parasite actin polymerization and filament structure.
AB  - A novel form of acto-myosin regulation has been proposed in which polymerization
      of new actin filaments regulates motility of parasites of the apicomplexan class
      of protozoa. In vivo and in vitro parasite F-actin is very short and unstable,
      but the structural basis and details of filament dynamics remain unknown. Here,
      we show that long actin filaments can be obtained by polymerizing unlabeled
      rabbit skeletal actin (RS-actin) onto both ends of the short rhodamine-phalloidin
      stabilized Plasmodium falciparum actin I (Pf-actin) filaments. Following
      annealing, hybrid filaments of micron length and "zebra-striped" appearance are
      observed by fluorescence microscopy that are stable enough to move over myosin
      class II motors in a gliding filament assay. Using negative stain electron
      microscopy we find that pure Pf-actin stabilized by jasplakinolide (JAS) also
      forms long filaments, indistinguishable in length from RS-actin filaments, and
      long enough to be characterized structurally. To compare structures in near
      physiological conditions in aqueous solution we imaged Pf-actin and RS-actin
      filaments by atomic force microscopy (AFM). We found the monomer stacking to be
      distinctly different for Pf-actin compared with RS-actin, such that the pitch of
      the double helix of Pf-actin filaments was 10% larger. Our results can be
      explained by a rotational angle between subunits that is larger in the parasite
      compared with RS-actin. Modeling of the AFM data using high-resolution actin
      filament models supports our interpretation of the data. The structural
      differences reported here may be a consequence of weaker inter- and intra-strand
      contacts, and may be critical for differences in filament dynamics and for
      regulation of parasite motility.

PMID- 20826800
TI  - The N terminus of a schistosome beta subunit regulates inactivation and current
      density of a Cav2 channel.
AB  - The beta subunit of high voltage-activated Ca(2+) (Ca(v)) channels targets the
      pore-forming alpha(1) subunit to the plasma membrane and tunes the biophysical
      phenotype of the Ca(v) channel complex. We used a combination of molecular
      biology and whole-cell patch clamp to investigate the functional role of a long N
      terminal polyacidic motif (NPAM) in a Ca(v)beta subunit of the human parasite
      Schistosoma mansoni (beta(Sm)), a motif that does not occur in other known
      Ca(v)beta subunits. When expressed in human embryonic kidney cells stably
      expressing Ca(v)2.3, beta(Sm) accelerates Ca(2+)/calmodulin-independent
      inactivation of Ca(v)2.3. Deleting the first 44 amino acids of beta(Sm), a region
      that includes NPAM, significantly slows the predominant time constant of
      inactivation (tau(fast)) under conditions that prevent Ca(2+)/CaM-dependent
      inactivation (beta(Sm): tau(fast) = 66 ms; beta(SmDelta2-44): tau(fast) = 111 ms,
      p < 0.01). Interestingly, deleting the amino acids that are N-terminal to NPAM (2
      24 or 2-17) results in faster inactivation than with an intact N terminus
      (tau(fast) = 42 ms with beta(SmDelta2-17); tau(fast) = 40 ms with beta(SmDelta2
      24), p < 0.01). This suggests that NPAM is the structural determinant for
      accelerating Ca(2+)/calmodulin-independent inactivation. We also created three
      chimeric subunits that contain the first 44 amino acids of beta(Sm) attached to
      mammalian beta(1b), beta(2a), and beta(3) subunits. For any given mammalian beta
      subunit, inactivation was faster if it contained the N terminus of beta(Sm) than
      if it did not. Co-expression of the mammalian alpha(2)delta-1 subunit resulted in
      doubling of the inactivation rate, but the effects of NPAM persisted. Thus, it
      appears that the schistosome Ca(v) channel complex has acquired a new function
      that likely contributes to reducing the amount of Ca(2+) that enters the cells in
      vivo. This feature is of potential interest as a target for new antihelminthics.

PMID- 20826801
TI  - The role of cis dimerization of signal regulatory protein alpha (SIRPalpha) in
      binding to CD47.
AB  - Interaction of SIRPalpha with its ligand, CD47, regulates leukocyte functions,
      including transmigration, phagocytosis, oxidative burst, and cytokine secretion.
      Recent progress has provided significant insights into the structural details of
      the distal IgV domain (D1) of SIRPalpha. However, the structural roles of
      proximal IgC domains (D2 and D3) have been largely unstudied. The high degree of
      conservation of D2 and D3 among members of the SIRP family as well as the
      propensity of known IgC domains to assemble in cis has led others to hypothesize
      that SIRPalpha forms higher order structures on the cell surface. Here we report
      that SIRPalpha forms noncovalently linked cis homodimers. Treatment of SIRPalpha
      expressing cells with a membrane-impermeable cross-linker resulted in the
      formation of SDS-stable SIRPalpha dimers and oligomers. Biochemical analyses of
      soluble recombinant extracellular regions of SIRPalpha, including domain
      truncation mutants, revealed that each of the three extracellular immunoglobulin
      loops of SIRPalpha formed dimers in solution. Co-immunoprecipitation experiments
      using cells transfected with different affinity-tagged SIRPalpha molecules
      revealed that SIRPalpha forms cis dimers. Interestingly, in cells treated with
      tunicamycin, SIRPalpha dimerization but not CD47 binding was inhibited,
      suggesting that a SIRPalpha dimer is probably bivalent. Last, we demonstrate
      robust dimerization of SIRPa in adherent, stimulated human neutrophils.
      Collectively, these data are consistent with SIRPalpha being expressed on the
      cell surface as a functional cis-linked dimer.

PMID- 20826803
TI  - Characterization of the yeast telomere nucleoprotein core: Rap1 binds
      independently to each recognition site.
AB  - At the core of Saccharomyces cerevisiae telomeres is an array of tandem telomeric
      DNA repeats bound site-specifically by multiple Rap1 molecules. There, Rap1
      orchestrates the binding of additional telomere-associated proteins and
      negatively regulates both telomere fusion and length homeostasis. Using electron
      microscopy, viscosity, and light scattering measurements, we show that purified
      Rap1 is a monomer in solution that adopts a ringlike or C shape with a central
      cavity. Rap1 could orchestrate telomere function by binding multiple telomere
      array sites through either cooperative or independent mechanisms. To determine
      the mechanism, we analyze the distribution of Rap1 monomers on defined telomeric
      DNA arrays. This analysis clearly indicates that Rap1 binds independently to each
      nonoverlapping site in an array, regardless of the spacing between sites, the
      total number of sites, the affinity of the sites for Rap1, and over a large
      concentration range. Previous experiments have not clearly separated the effects
      of affinity from repeat spacing on telomere function. We clarify these results by
      testing in vivo the function of defined telomere arrays containing the same Rap1
      binding site separated by spacings that were previously defined as low or high
      activity. We find that Rap1 binding affinity in vitro correlates with the ability
      of telomeric repeat arrays to regulate telomere length in vivo. We suggest that
      Rap1 binding to multiple sites in a telomere array does not, by itself, promote
      formation of a more energetically stabile complex.

PMID- 20826802
TI  - MicroRNA-223 regulates cyclin E activity by modulating expression of F-box and WD
      40 domain protein 7.
AB  - F-box and WD-40 domain protein 7 (Fbw7) provides substrate specificity for the
      Skp1-Cullin1-F-box protein (SCF) ubiquitin ligase complex that targets multiple
      oncoproteins for degradation, including cyclin E, c-Myc, c-Jun, Notch, and
      mammalian target of rapamycin (mTOR). Fbw7 is a bona fide tumor suppressor, and
      loss-of-function mutations in FBXW7 have been identified in diverse human tumors.
      Although much is known about targets of the Fbw7 ubiquitin ligase pathway,
      relatively little is known about the regulation of Fbw7 expression. We identified
      a panel of candidate microRNA regulators of Fbw7 expression within a study of
      gene expression alterations in primary erythroblasts obtained from cyclin E(T74A
      T393A) knock-in mice, which have markedly dysregulated cyclin E expression. We
      found that overexpression of miR-223, in particular, significantly reduces FBXW7
      mRNA levels, increases endogenous cyclin E protein and activity levels, and
      increases genomic instability. We next confirmed that miR-223 targets the FBXW7
      3'-untranslated region. We then found that reduced miR-223 expression in primary
      mouse embryonic fibroblasts leads to increased Fbw7 expression and decreased
      cyclin E activity. Finally, we found that miR-223 expression is responsive to
      acute alterations in cyclin E regulation by the Fbw7 pathway. Together, our data
      indicate that miR-223 regulates Fbw7 expression and provide the first evidence
      that activity of the SCF(Fbw7) ubiquitin ligase can be modulated directly by the
      microRNA pathway.

PMID- 20826804
TI  - The archaeal Lsm protein binds to small RNAs.
AB  - Proteins of the Lsm family, including eukaryotic Sm proteins and bacterial Hfq,
      are key players in RNA metabolism. Little is known about the archaeal homologues
      of these proteins. Therefore, we characterized the Lsm protein from the
      haloarchaeon Haloferax volcanii using in vitro and in vivo approaches. H.
      volcanii encodes a single Lsm protein, which belongs to the Lsm1 subfamily. The
      lsm gene is co-transcribed and overlaps with the gene for the ribosomal protein
      L37e. Northern blot analysis shows that the lsm gene is differentially
      transcribed. The Lsm protein forms homoheptameric complexes and has a copy number
      of 4000 molecules/cell. In vitro analyses using electrophoretic mobility shift
      assays and ultrasoft mass spectrometry (laser-induced liquid bead ion desorption)
      showed a complex formation of the recombinant Lsm protein with oligo(U)-RNA,
      tRNAs, and an small RNA. Co-immunoprecipitation with a FLAG-tagged Lsm protein
      produced in vivo confirmed that the protein binds to small RNAs. Furthermore, the
      co-immunoprecipitation revealed several protein interaction partners, suggesting
      its involvement in different cellular pathways. The deletion of the lsm gene is
      viable, resulting in a pleiotropic phenotype, indicating that the haloarchaeal
      Lsm is involved in many cellular processes, which is in congruence with the
      number of protein interaction partners.

PMID- 20826805
TI  - Fission yeast germinal center (GC) kinase Ppk11 interacts with Pmo25 and plays an
      auxiliary role in concert with the morphogenesis Orb6 network (MOR) in cell
      morphogenesis.
AB  - How cell morphology and the cell cycle are coordinately regulated is a
      fundamental subject in cell biology. In fission yeast, 2 germinal center kinases
      (GCKs), Sid1 and Nak1, play an essential role in septation/cytokinesis and cell
      separation/cell polarity control, respectively, as components of the septation
      initiation network (SIN) and the morphogenesis Orb6 network (MOR). Here we show
      that a third GCK, Ppk11, is also required for efficient cell separation
      particularly, at a high temperature. Although Ppk11 is not essential for cell
      division, this kinase plays an auxiliary role in concert with MOR in cell
      morphogenesis. Ppk11 physically interacts with the MOR component Pmo25 and is
      localized to the septum, by which Ppk11 is crucial for Pmo25
      targeting/accumulation to the septum. The conserved C-terminal WDF motif of Ppk11
      is essential for both septum accumulation of Pmo25 and efficient cell separation.
      In contrast its kinase activity is required only for cell separation. Thus, both
      interaction of Ppk11 with Pmo25 and Ppk11 kinase activity are critical for
      efficient cell separation.

PMID- 20826806
TI  - Cyclin-dependent kinase 5 regulates endothelial cell migration and angiogenesis.
AB  - Angiogenesis contributes to various pathological conditions. Due to the
      resistance against existing antiangiogenic therapy, an urgent need exists to
      understand the molecular basis of vessel growth and to identify new targets for
      antiangiogenic therapy. Here we show that cyclin-dependent kinase 5 (Cdk5), an
      important modulator of neuronal processes, regulates endothelial cell migration
      and angiogenesis, suggesting Cdk5 as a novel target for antiangiogenic therapy.
      Inhibition or knockdown of Cdk5 reduces endothelial cell motility and blocks
      angiogenesis in vitro and in vivo. We elucidate a specific signaling of Cdk5 in
      the endothelium; in contrast to neuronal cells, the motile defects upon
      inhibition of Cdk5 are not caused by an impaired function of focal adhesions or
      microtubules but by the reduced formation of lamellipodia. Inhibition or down
      regulation of Cdk5 decreases the activity of the small GTPase Rac1 and results in
      a disorganized actin cytoskeleton. Constitutive active Rac1 compensates for the
      inhibiting effects of Cdk5 knockdown on migration, suggesting that Cdk5 exerts
      its effects in endothelial cell migration via Rac1. Our work elucidates Cdk5 as a
      pivotal new regulator of endothelial cell migration and angiogenesis. It suggests
      Cdk5 as a novel, pharmacologically accessible target for antiangiogenic therapy
      and provides the basis for a new therapeutic application of Cdk5 inhibitors as
      antiangiogenic agents.

PMID- 20826807
TI  - Isolation of mutant alginate lyases with cleavage specificity for di-guluronic
      acid linkages.
AB  - Alginates are commercially valuable and complex polysaccharides composed of
      varying amounts and distribution patterns of 1-4-linked beta-D-mannuronic acid
      (M) and alpha-L-guluronic acid (G). This structural variability strongly affects
      polymer physicochemical properties and thereby both commercial applications and
      biological functions. One promising approach to alginate fine structure
      elucidation involves the use of alginate lyases, which degrade the polysaccharide
      by cleaving the glycosidic linkages through a beta-elimination reaction. For such
      studies one would ideally like to have different lyases, each of which cleaves
      only one of the four possible linkages in alginates: G-G, G-M, M-G, and M-M. So
      far no lyase specific for only G-G linkages has been described, and here we
      report the construction of such an enzyme by mutating the gene encoding
      Klebsiella pneumoniae lyase AlyA (a polysaccharide lyase family 7 lyase), which
      cleaves both G-G and G-M linkages. After error-prone PCR mutagenesis and high
      throughput screening of ~7000 lyase mutants, enzyme variants with a strongly
      improved G-G specificity were identified. Furthermore, in the absence of Ca(2+),
      one of these lyases (AlyA5) was found to display no detectable activity against G
      M linkages. G-G linkages were cleaved with ~10% of the optimal activity under the
      same conditions. The substitutions conferring altered specificity to the mutant
      enzymes are located in conserved regions in the polysaccharide lyase family 7
      alginate lyases. Structure-function analyses by comparison with the known three
      dimensional structure of Sphingomonas sp. A1 lyase A1-II' suggests that the
      improved G-G specificity might be caused by increased affinity for nonproductive
      binding of the alternating G-M structure.

PMID- 20826808
TI  - A crystal structure of the cyclic GMP-dependent protein kinase I{beta}
      dimerization/docking domain reveals molecular details of isoform-specific
      anchoring.
AB  - Cyclic GMP-dependent protein kinase (PKG) is a key mediator of the nitric
      oxide/cGMP signaling pathway and plays a central role in regulating
      cardiovascular and neuronal functions. The N-terminal ~50 amino acids of the
      kinase are required for homodimerization and association with isoform-specific
      PKG-anchoring proteins (GKAPs), which target the kinase to specific substrates.
      To understand the molecular details of PKG dimerization and gain insight into its
      association with GKAPs, we solved a crystal structure of the PKG Ibeta
      dimerization/docking domain. Our structure provides molecular details of this
      unique leucine/isoleucine zipper, revealing specific hydrophobic and ionic
      interactions that mediate dimerization and demonstrating the topology of the GKAP
      interaction surface.

PMID- 20826809
TI  - sFRP2 suppression of bone morphogenic protein (BMP) and Wnt signaling mediates
      mesenchymal stem cell (MSC) self-renewal promoting engraftment and myocardial
      repair.
AB  - Transplantation of mesenchymal stem cells (MSCs) is a promising therapy for
      ischemic injury; however, inadequate survival of implanted cells in host tissue
      is a substantial impediment in the progress of cellular therapy. Secreted
      Frizzled-related protein 2 (sFRP2) has recently been highlighted as a key
      mediator of MSC-driven myocardial and wound repair. Notably, sFRP2 mediates
      significant enhancement of MSC engraftment in vivo. We hypothesized that sFRP2
      improves MSC engraftment by modulating self-renewal through increasing stem cell
      survival and by inhibiting differentiation. In previous studies we demonstrated
      that sFRP2-expressing MSCs exhibited an increased proliferation rate. In the
      current study, we show that sFRP2 also decreased MSC apoptosis and inhibited both
      osteogenic and chondrogenic lineage commitment. sFRP2 activity occurred through
      the inhibition of both Wnt and bone morphogenic protein (BMP) signaling pathways.
      sFRP2-mediated inhibition of BMP signaling, as assessed by levels of pSMAD 1/5/8,
      was independent of its effects on the Wnt pathway. We further hypothesized that
      sFRP2 inhibition of MSC lineage commitment may reduce heterotopic osteogenic
      differentiation within the injured myocardium, a reported adverse side effect.
      Indeed, we found that sFRP2-MSC-treated hearts and wound tissue had less ectopic
      calcification. This work provides important new insight into the mechanisms by
      which sFRP2 increases MSC self-renewal leading to superior tissue engraftment and
      enhanced wound healing.

PMID- 20826810
TI  - Structural and kinetic analysis of Bacillus subtilis N-acetylglucosaminidase
      reveals a unique Asp-His dyad mechanism.
AB  - Three-dimensional structures of NagZ of Bacillus subtilis, the first structures
      of a two-domain beta-N-acetylglucosaminidase of family 3 of glycosidases, were
      determined with and without the transition state mimicking inhibitor PUGNAc bound
      to the active site, at 1.84- and 1.40-A resolution, respectively. The structures
      together with kinetic analyses of mutants revealed an Asp-His dyad involved in
      catalysis: His(234) of BsNagZ acts as general acid/base catalyst and is hydrogen
      bonded by Asp(232) for proper function. Replacement of both His(234) and Asp(232)
      with glycine reduced the rate of hydrolysis of the fluorogenic substrate 4'
      methylumbelliferyl N-acetyl-beta-D-glucosaminide 1900- and 4500-fold,
      respectively, and rendered activity pH-independent in the alkaline range
      consistent with a role of these residues in acid/base catalysis. N
      Acetylglucosaminyl enzyme intermediate accumulated in the H234G mutant and beta
      azide product was formed in the presence of sodium azide in both mutants. The Asp
      His dyad is conserved within beta-N-acetylglucosaminidases but otherwise absent
      in beta-glycosidases of family 3, which instead carry a "classical" glutamate
      acid/base catalyst. The acid/base glutamate of Hordeum vulgare exoglucanase
      (Exo1) superimposes with His(234) of the dyad of BsNagZ and, in contrast to the
      latter, protrudes from a second domain of the enzyme into the active site. This
      is the first report of an Asp-His catalytic dyad involved in hydrolysis of
      glycosides resembling in function the Asp-His-Ser triad of serine proteases. Our
      findings will facilitate the development of mechanism-based inhibitors that
      selectively target family 3 beta-N-acetylglucosaminidases, which are involved in
      bacterial cell wall turnover, spore germination, and induction of beta-lactamase.

PMID- 20826811
TI  - miR-200a regulates epithelial-mesenchymal to stem-like transition via ZEB2 and
      beta-catenin signaling.
AB  - The emerging concept of generating cancer stem cells from epithelial-mesenchymal
      transition has attracted great interest; however, the factors and molecular
      mechanisms that govern this putative tumor-initiating process remain largely
      elusive. We report here that miR-200a not only regulates epithelial-mesenchymal
      transition but also stem-like transition in nasopharyngeal carcinoma cells. We
      first showed that stable knockdown of miR-200a promotes the transition of
      epithelium-like CNE-1 cells to the mesenchymal phenotype. More importantly, it
      also induced several stem cell-like traits, including CD133(+) side population,
      sphere formation capacity, in vivo tumorigenicity in nude mice, and stem cell
      marker expression. Consistently, stable overexpression of miR-200a switched
      mesenchyme-like C666-1 cells to the epithelial state, accompanied by a
      significant reduction of stem-like cell features. Furthermore, in vitro
      differentiation of the C666-1 tumor sphere resulted in diminished stem-like cell
      population and miR-200a induction. To investigate the molecular mechanism, we
      demonstrated that miR-200a controls epithelial-mesenchymal transition by
      targeting ZEB2, although it regulates the stem-like transition differentially and
      specifically by beta-catenin signaling. Our findings reveal for the first time
      the function of miR-200a in shifting nasopharyngeal carcinoma cell states via a
      reversible process coined as epithelial-mesenchymal to stem-like transition
      through differential and specific mechanisms.

PMID- 20826812
TI  - Redox regulation of lipopolysaccharide-mediated sulfiredoxin induction, which
      depends on both AP-1 and Nrf2.
AB  - Sulfiredoxin (Srx) is an enzyme that catalyzes the reduction of cysteine sulfinic
      acid of hyperoxidized peroxiredoxins and exerts a protective antioxidant role.
      Here we investigated the regulatory mechanism of Srx induction by
      lipopolysaccharide (LPS) in mouse macrophages. LPS up-regulated Srx expression on
      the transcriptional level. The promoter region of the Srx gene contained putative
      NF-kappaB and AP-1 (activator protein-1) sites, and the proximal site of three AP
      1 sites was embedded within the antioxidant response element (ARE), a cis-acting
      element for Nrf2 (nuclear factor erythroid 2-related factor). Mutational analysis
      of the Srx promoter revealed that Srx induction is dependent on AP-1 sites and
      ARE but not on NF-kappaB sites. Consistently, both transcription factors, AP-1
      and Nrf2, were required for LPS-mediated Srx induction, as revealed by chromatin
      immunoprecipitation using antibodies specific for c-Jun and c-Fos and little Srx
      induction in Nrf2-null bone marrow-derived macrophages. Among mitogen-activated
      protein kinases that mediate the signal transduction by LPS, JNK played a major
      role in Srx induction. Moreover, chemical antioxidants, such as N-acetylcysteine
      and butylated hydroxyanisole, and the NADPH oxidase inhibitor diphenyleneiodonium
      inhibited Srx induction as well as generation of reactive oxygen species, both of
      which were also suppressed in Nox2 (NADPH oxidase 2)-deficient bone marrow
      derived macrophages. These results suggest that LPS-mediated Srx induction is
      dependent on both AP-1 and Nrf2, which is regulated by Nox2-derived reactive
      oxygen species.

PMID- 20826814
TI  - Recognition of the helical structure of beta-1,4-galactan by a new family of
      carbohydrate-binding modules.
AB  - The microbial enzymes that depolymerize plant cell wall polysaccharides,
      ultimately promoting energy liberation and carbon recycling, are typically
      complex in their modularity and often contain carbohydrate-binding modules
      (CBMs). Here, through analysis of an unknown module from a Thermotoga maritima
      endo-beta-1,4-galactanase, we identify a new family of CBMs that are most
      frequently found appended to proteins with beta-1,4-galactanase activity.
      Polysaccharide microarray screening, immunofluorescence microscopy, and
      biochemical analysis of the isolated module demonstrate the specificity of the
      module, here called TmCBM61, for beta-1,4-linked galactose-containing ligands,
      making it the founding member of family CBM61. The ultra-high resolution X-ray
      crystal structures of TmCBM61 (0.95 and 1.4 A resolution) in complex with beta
      1,4-galactotriose reveal the molecular basis of the specificity of the CBM for
      beta-1,4-galactan. Analysis of these structures provides insight into the
      recognition of an unexpected helical galactan conformation through a mode of
      binding that resembles the recognition of starch.

PMID- 20826813
TI  - Endocannabinoids are expressed in bone marrow stromal niches and play a role in
      interactions of hematopoietic stem and progenitor cells with the bone marrow
      microenvironment.
AB  - Endocannabinoids are lipid signaling molecules that act via G-coupled receptors,
      CB(1) and CB(2). The endocannabinoid system is capable of activation of distinct
      signaling pathways on demand in response to pathogenic events or stimuli, hereby
      enhancing cell survival and promoting tissue repair. However, the role of
      endocannabinoids in hematopoietic stem and progenitor cells (HSPCs) and their
      interaction with hematopoietic stem cells (HSC) niches is not known. HSPCs are
      maintained in the quiescent state in bone marrow (BM) niches by intrinsic and
      extrinsic signaling. We report that HSPCs express the CB(1) receptors and that BM
      stromal cells secrete endocannabinoids, anandamide (AEA) (35 pg/10(7) cells), and
      2-AG (75.2 ng/10(7) cells). In response to the endotoxin lipopolysaccharide
      (LPS), elevated levels of AEA (75.6 pg/10(7) cells) and 2-AG (98.8 ng/10(7)
      cells) were secreted from BM stromal cells, resulting in migration and
      trafficking of HSPCs from the BM niches to the peripheral blood. Furthermore,
      administration of exogenous cannabinoid CB(1) agonists in vivo induced
      chemotaxis, migration, and mobilization of human and murine HSPCs. Cannabinoid
      receptor knock-out mice Cnr1(-/-) showed a decrease in side population (SP)
      cells, whereas fatty acid amide hydrolase (FAAH)(-/-) mice, which have elevated
      levels of AEA, yielded increased colony formation as compared with WT mice. In
      addition, G-CSF-induced mobilization in vivo was modulated by endocannabinoids
      and was inhibited by specific cannabinoid antagonists as well as impaired in
      cannabinoid receptor knock-out mice Cnr1(-/-), as compared with WT mice. Thus, we
      propose a novel function of the endocannabinoid system, as a regulator of HSPC
      interactions with their BM niches, where endocannabinoids are expressed in HSC
      niches and under stress conditions, endocannabinoid expression levels are
      enhanced to induce HSPC migration for proper hematopoiesis.

PMID- 20826815
TI  - Syntaxin 16 binds to cystic fibrosis transmembrane conductance regulator and
      regulates its membrane trafficking in epithelial cells.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a key membrane
      protein in the complex network of epithelial ion transporters regulating
      epithelial permeability. Syntaxins are one of the major determinants in the
      intracellular trafficking and membrane targeting of secretory proteins. In the
      present study we demonstrate the biochemical and functional association between
      CFTR and syntaxin 16 (STX16) that mediates vesicle transport within the
      early/late endosomes and trans-Golgi network. Immunoprecipitation experiments in
      rat colon and T84 human colonic epithelial cells indicate that STX16 associates
      with CFTR. Further analyses using the domain-specific pulldown assay reveal that
      the helix domain of STX16 directly interacts with the N-terminal region of CFTR.
      Immunostainings in rat colon and T84 cells show that CFTR and STX16 highly co
      localize at the apical and subapical regions of epithelial cells. Interestingly,
      CFTR-associated chloride current was reduced by the knockdown of STX16 expression
      in T84 cells. Surface biotinylation and recycling assays indicate that the
      reduction in CFTR chloride current is due to decreased CFTR expression on the
      plasma membrane. These results suggest that STX16 mediates recycling of CFTR and
      constitutes an important component of CFTR trafficking machinery in intestinal
      epithelial cells.

PMID- 20826816
TI  - The anti-inflammatory drug indomethacin alters nanoclustering in synthetic and
      cell plasma membranes.
AB  - The nonsteroidal anti-inflammatory drug indomethacin exhibits diverse biological
      effects, many of which have no clear molecular mechanism. Membrane-bound
      receptors and enzymes are sensitive to their phospholipid microenvironment.
      Amphipathic indomethacin could therefore potentially modulate cell signaling by
      changing membrane properties. Here we examined the effect of indomethacin on
      membrane lateral heterogeneity. Fluorescence lifetime imaging of cells expressing
      lipid-anchored probes revealed that treatment of BHK cells with therapeutic
      levels of indomethacin enhances cholesterol-dependent nanoclustering, but not
      cholesterol-independent nanoclustering. Immuno-electron microscopy and
      quantitative spatial mapping of intact plasma membrane sheets similarly showed a
      selective effect of indomethacin on promoting cholesterol-dependent, but not
      cholesterol-independent, nanoclustering. To further evaluate the biophysical
      effects of indomethacin, we measured fluorescence polarization of the phase
      sensitive probe Laurdan and FRET between phase-partitioning probes in model
      bilayers. Therapeutic levels of indomethacin enhanced phase separation in
      DPPC/DOPC/Chol (1:1:1) and DPPC/Chol membranes in a temperature-dependent manner,
      but had minimal effect on the phase behavior of pure DOPC at any temperature.
      Taken together, the imaging results on intact epithelial cells and the
      biophysical assays of model membranes suggest that indomethacin can enhance phase
      separation and stabilize cholesterol-dependent nanoclusters in biological
      membranes. These effects on membrane lateral heterogeneity may have significant
      consequences for cell signaling cascades that are assembled on the plasma
      membrane.

PMID- 20826817
TI  - Regulation of yeast nutrient permease endocytosis by ATP-binding cassette
      transporters and a seven-transmembrane protein, RSB1.
AB  - Ceramide is produced by the condensation of a long chain base with a very long
      chain fatty acid. In Saccharomyces cerevisiae, one of the two major long chain
      bases is called phytosphingosine (PHS). PHS has been shown to cause toxicity in
      tryptophan auxotrophic strains of yeast because this bioactive ceramide precursor
      causes diversion of the high affinity tryptophan permease Tat2 to the vacuole
      rather than the plasma membrane. Loss of the integral membrane protein Rsb1
      increased PHS sensitivity, which was suggested to be due to this protein acting
      as an ATP-dependent long chain base efflux protein. More recent experiments
      demonstrated that loss of the genes encoding the ATP-binding cassette transporter
      proteins Pdr5 and Yor1 elevated PHS tolerance. This increased resistance was
      suggested to be due to increased expression of RSB1. Here, we provide an
      alternative view of PHS resistance influenced by Rsb1 and Pdr5/Yor1. Rsb1 has a
      seven-transmembrane domain topology more consistent with that of a regulatory
      protein like a G-protein-coupled receptor rather than a transporter. Importantly,
      an rsb1Delta cell does not exhibit higher internal levels of PHS compared with
      isogenic wild-type cells. However, tryptophan transport is increased in pdr5Delta
      yor1 strains and reduced in rsb1Delta cells. Localization and vacuolar
      degradation of Tat2 are affected in these genetic backgrounds. Finally,
      internalization of FM4-64 dye suggests that loss of Pdr5 and Yor1 slows normal
      endocytic rates. Together, these data argue that Rsb1, Pdr5, and Yor1 regulate
      the endocytosis of Tat2 and likely other membrane transporter proteins.

PMID- 20826818
TI  - Novel interactions of CAPS (Ca2+-dependent activator protein for secretion) with
      the three neuronal SNARE proteins required for vesicle fusion.
AB  - CAPS (aka CADPS) is required for optimal vesicle exocytosis in neurons and
      endocrine cells where it functions to prime the exocytic machinery for Ca(2+)
      triggered fusion. Fusion is mediated by trans complexes of the SNARE proteins
      VAMP-2, syntaxin-1, and SNAP-25 that bridge vesicle and plasma membrane. CAPS
      promotes SNARE complex formation on liposomes, but the SNARE binding properties
      of CAPS are unknown. The current work revealed that CAPS exhibits high affinity
      binding to syntaxin-1 and SNAP-25 and moderate affinity binding to VAMP-2. CAPS
      binding is specific for a subset of exocytic SNARE protein isoforms and requires
      membrane integration of the SNARE proteins. SNARE protein binding by CAPS is
      novel and mediated by interactions with the SNARE motifs in the three proteins.
      The C-terminal site for CAPS binding on syntaxin-1 does not overlap the Munc18-1
      binding site and both proteins can co-reside on membrane-integrated syntaxin-1.
      As expected for a C-terminal binding site on syntaxin-1, CAPS stimulates SNARE
      dependent liposome fusion with N-terminal truncated syntaxin-1 but exhibits
      impaired activity with C-terminal syntaxin-1 mutants. Overall the results suggest
      that SNARE complex formation promoted by CAPS may be mediated by direct
      interactions of CAPS with each of the three SNARE proteins required for vesicle
      exocytosis.

PMID- 20826819
TI  - Structural studies and the assembly of the heptameric post-translational
      translocon complex.
AB  - In Saccharomyces cerevisiae, some of the nascent chains can be post
      translationally translocated into the endoplasmic reticulum through the
      heptameric post-translational translocon complex (post-translocon). This membrane
      protein complex is composed of the protein-conducting channel and the tetrameric
      Sec62/63 complex. The Sec62/63 complex plays crucial roles in targeting of the
      signal recognition particle-independent protein substrate to the protein
      conducting channel and in assembly of the post-translocon. Although the molecular
      mechanism of the post-translational translocation process has been well
      established, the structure of the post-translocon and how the channel and the
      Sec62/63 complex form the heptameric complex are largely uncharacterized. Here,
      we report a 20-A resolution cryo-electron microscopy structure of the post
      translocon. The purified post-translocon was found to have a mass of 287 kDa,
      which is consistent with the unit stoichiometry of the seven subunits as
      determined by a cysteine labeling experiment. We demonstrated that Triton X-100
      dissociated the heptameric complex into three subcomplexes identified as the
      trimeric translocon Sec61-Sbh1-Sss1, the Sec63-Sec71-Sec72 trimer, and the
      heterotetramer Sec62-Sec63-Sec71-Sec72, respectively. Additionally, a role of the
      sixth cytosolic loop of Sec61 in assembly of the post-translocon was
      demonstrated. Mutations of conserved, positively charged amino acid residues in
      the loop caused decreased formation of the post-translocon. These studies provide
      the first architectural description of the yeast post-translocon.

PMID- 20826820
TI  - Biochemical characterization of the transcriptional regulator BzdR from Azoarcus
      sp. CIB.
AB  - The BzdR transcriptional regulator that controls the P(N) promoter responsible
      for the anaerobic catabolism of benzoate in Azoarcus sp. CIB constitutes the
      prototype of a new subfamily of transcriptional regulators. Here, we provide some
      insights about the functional-structural relationships of the BzdR protein.
      Analytical ultracentrifugation studies revealed that BzdR is homodimeric in
      solution. An electron microscopy three-dimensional reconstruction of the BzdR
      dimer has been obtained, and the predicted structures of the respective N- and C
      terminal domains of each BzdR monomer could be fitted into such a reconstruction.
      Gel retardation and ultracentrifugation experiments have shown that the binding
      of BzdR to its cognate promoter is cooperative. Different biochemical approaches
      revealed that the effector molecule benzoyl-CoA induces conformational changes in
      BzdR without affecting its oligomeric state. The BzdR-dependent inhibition of the
      P(N) promoter and its activation in the presence of benzoyl-CoA have been
      established by in vitro transcription assays. The monomeric BzdR4 and BzdR5
      mutant regulators revealed that dimerization of BzdR is essential for DNA
      binding. Remarkably, a BzdRDeltaL protein lacking the linker region connecting
      the N- and C-terminal domains of BzdR is also dimeric and behaves as a super
      repressor of the P(N) promoter. These data suggest that the linker region of BzdR
      is not essential for protein dimerization, but rather it is required to transfer
      the conformational changes induced by the benzoyl-CoA to the DNA binding domain
      leading to the release of the repressor. A model of action of the BzdR regulator
      has been proposed.

PMID- 20826821
TI  - Lamin B counteracts the kinesin Eg5 to restrain spindle pole separation during
      spindle assembly.
AB  - Lamin B is a component of the membranous spindle matrix isolated from Xenopus egg
      extracts, and it is required for proper spindle morphogenesis. Besides lamin B,
      the spindle matrix contains spindle assembly factors (SAFs) such as Eg5 and
      dynein which are known to regulate microtubule organization and SAFs known to
      promote microtubule assembly such as Maskin and XMAP215. Because lamin B does not
      bind directly to microtubules, it must affect spindle morphogenesis indirectly by
      influencing the function of spindle matrix-associated SAFs. Using different
      assays in Xenopus egg extracts, we found that depleting lamin B caused formation
      of elongated and multipolar spindles, which could be reversed by partially
      inhibiting the kinesin Eg5, revealing an antagonistic relationship between Eg5
      and lamin B. However, lamin B only very weakly antagonizes Eg5 in mediating
      poleward microtubule-flux based on fluorescence speckle microscopy. Depleting
      lamin B led to a very small but statistically significant increase in flux.
      Furthermore, flux reduction caused by partial Eg5 inhibition is only slightly
      reversed by removing lamin B. Because lamin B does not bind to Eg5, our studies
      suggest two nonexclusive mechanisms by which lamin B can indirectly antagonize
      Eg5. It could function in a network that restricts Eg5-driven microtubule sliding
      only when microtubules come into transient contact with the network. Lamin B
      could also function to sequester microtubule polymerization activities within the
      spindle. Without lamin B, increased microtubule assembly caused by the released
      SAFs would lead to excessive microtubule sliding that results in formation of
      elongated and multipolar spindles.

PMID- 20826822
TI  - The dithiol glutaredoxins of african trypanosomes have distinct roles and are
      closely linked to the unique trypanothione metabolism.
AB  - Trypanosoma brucei, the causative agent of African sleeping sickness, possesses
      two dithiol glutaredoxins (Grx1 and Grx2). Grx1 occurs in the cytosol and
      catalyzes protein deglutathionylations with k(cat)/K(m)-values of up to 2 * 10(5)
      M(-1) S(-1). It accelerates the reduction of ribonucleotide reductase by
      trypanothione although less efficiently than the parasite tryparedoxin and has
      low insulin disulfide reductase activity. Despite its classical CPYC active site,
      Grx1 forms dimeric iron-sulfur complexes with GSH, glutathionylspermidine, or
      trypanothione as non-protein ligands. Thus, contrary to the generally accepted
      assumption, replacement of the Pro is not a prerequisite for cluster formation.
      T. brucei Grx2 shows an unusual CQFC active site, and orthologues occur
      exclusively in trypanosomatids. Grx2 is enriched in mitoplasts, and fractionated
      digitonin lysis resulted in a co-elution with cytochrome c, suggesting
      localization in the mitochondrial intermembrane space. Grx2 catalyzes the
      reduction of insulin disulfide but not of ribonucleotide reductase and exerts
      deglutathionylation activity 10-fold lower than that of Grx1. RNA interference
      against Grx2 caused a growth retardation of procyclic cells consistent with an
      essential role. Grx1 and Grx2 are constitutively expressed with cellular
      concentrations of about 2 MUM and 200 nM, respectively, in both the mammalian
      bloodstream and insect procyclic forms. Trypanothione reduces the disulfide form
      of both proteins with apparent rate constants that are 3 orders of magnitude
      higher than those with glutathione. Grx1 and, less efficiently, also Grx2
      catalyze the reduction of GSSG by trypanothione. Thus, the Grxs play exclusive
      roles in the trypanothione-based thiol redox metabolism of African trypanosomes.

PMID- 20826823
TI  - The N domain of human angiotensin-I-converting enzyme: the role of N
      glycosylation and the crystal structure in complex with an N domain-specific
      phosphinic inhibitor, RXP407.
AB  - Angiotensin-I-converting enzyme (ACE) plays a critical role in the regulation of
      blood pressure through its central role in the renin-angiotensin and kallikrein
      kinin systems. ACE contains two domains, the N and C domains, both of which are
      heavily glycosylated. Structural studies of ACE have been fraught with severe
      difficulties because of surface glycosylation of the protein. In order to
      investigate the role of glycosylation in the N domain and to create suitable
      forms for crystallization, we have investigated the importance of the 10
      potential N-linked glycan sites using enzymatic deglycosylation, limited
      proteolysis, and mass spectrometry. A number of glycosylation mutants were
      generated via site-directed mutagenesis, expressed in CHO cells, and analyzed for
      enzymatic activity and thermal stability. At least eight of 10 of the potential
      glycan sites are glycosylated; three C-terminal sites were sufficient for
      expression of active N domain, whereas two N-terminal sites are important for its
      thermal stability. The minimally glycosylated Ndom389 construct was highly
      suitable for crystallization studies. The structure in the presence of an N
      domain-selective phosphinic inhibitor RXP407 was determined to 2.0 A resolution.
      The Ndom389 structure revealed a hinge region that may contribute to the
      breathing motion proposed for substrate binding.

PMID- 20826825
TI  - Characterization of the secondary binding sites of Maclura pomifera agglutinin by
      glycan array and crystallographic analyses.
AB  - The Maclura pomifera agglutinin (MPA) recognizes the T-antigen disaccharide
      Galbeta1,3GalNAc mainly through interaction of the alpha-GalNAc moiety with its
      primary site, but the interactions of the two flanking subsites A and B with
      aglycones and substituents other than Gal, respectively, are not well understood.
      We therefore characterized the specificity of MPA in more detail by glycan
      microarray analysis and determined the crystal structures of MPA without ligand
      and in complexes with Galbeta1,3GalNAc and p-nitrophenyl alpha-GalNAc. In both
      sugar complexes, pairs of ligands created inter-tetramer hydrogen-bond bridging
      networks. While subsite A showed increased affinity for hydrophobic aglycones, it
      also accommodated several sugar substituents. Notably, a GalNAc-O-tripeptide, a
      Tn-antigen mimic, showed lower affinity than these compounds in surface plasmon
      resonance (SPR) experiments. The glycan array data that showed subsite B accepted
      compounds in which the O3 position of the GalNAc was substituted with various
      sugars other than Gal, but substitutions at O6 led to inactivity. Additions to
      the Gal moiety of the disaccharide also had only small effects on reactivity.
      These results are all compatible with the features seen in the crystal
      structures.

PMID- 20826824
TI  - Stabilized HIV-1 envelope glycoprotein trimers lacking the V1V2 domain, obtained
      by virus evolution.
AB  - The envelope glycoproteins (Env) are the focus of HIV-1 vaccine development
      strategies based on the induction of humoral immunity, but the mechanisms the
      virus has evolved to limit the induction and binding of neutralizing antibodies
      (NAbs) constitute substantial obstacles. Conserved neutralization epitopes are
      shielded by variable regions and carbohydrates, so one strategy to increase their
      exposure and, it is hoped, their immunogenicity is to delete the overlying
      variable loops. However, deleting the variable regions from Env trimers can be
      problematic, because hydrophobic patches that are normally solvent-inaccessible
      now become exposed, causing protein misfolding or aggregation, for example. Here,
      we describe the construction and characterization of recombinant gp140 trimers
      lacking variable domains 1 and 2 (DeltaV1V2). The design of the trimers was
      guided by HIV-1 evolution studies that identified compensatory changes in V1V2
      deleted but functional Env proteins (Bontjer, I., Land, A., Eggink, D., Verkade,
      E., Tuin, K., Baldwin, C., Pollakis, G., Paxton, W. A., Braakman, I., Berkhout,
      B., and Sanders, R. W. (2009) J. Virol. 83, 368-383). We now show that specific
      compensatory changes improved the function of DeltaV1V2 Env proteins and hence
      HIV-1 replication. The changes acted by reducing the exposure of a hydrophobic
      surface either by replacing a hydrophobic residue with a hydrophilic one or by
      covering the surface with a glycan. The compensatory changes allowed the
      efficient expression of well folded, soluble gp140 trimers derived from various
      HIV-1 isolates. The evolved DeltaV1V2 Env viruses were extremely sensitive to
      NAbs, indicating that neutralization epitopes are well exposed, which was
      confirmed by studies of NAb binding to the soluble DeltaV1V2 gp140 trimers. These
      evolved DeltaV1V2 trimers could be useful reagents for immunogenicity and
      structural studies.

PMID- 20826827
TI  - Context-dependent effects of genome-wide association study genotypes and
      macroenvironment on time to biochemical (prostate specific antigen) failure after
      prostatectomy.
AB  - BACKGROUND: Disparities in cancer defined by race, age, or gender are well
      established. However, demographic metrics are surrogates for the complex
      contributions of genotypes, exposures, health care, socioeconomic and
      sociocultural environment, and many other factors. Macroenvironmental factors
      represent novel surrogates for exposures, lifestyle, and other factors that are
      difficult to measure but might influence cancer outcomes. METHODS: We applied a
      "multilevel molecular epidemiology" approach using a prospective cohort of 444
      White prostate cancer cases who underwent prostatectomy and were followed until
      biochemical failure (BF) or censoring without BF. We applied Cox regression
      models to test for joint effects of 86 genome-wide association study-identified
      genotypes and macroenvironment contextual effects after geocoding all cases to
      their residential census tracts. All analyses were adjusted for age at diagnosis
      and tumor aggressiveness. RESULTS: Residents living in census tracts with a high
      proportion of older single heads of household, high rates of vacant housing, or
      high unemployment had shorter time until BF postsurgery after adjustment for
      patient age and tumor aggressiveness. After correction for multiple testing,
      genotypes alone did not predict time to BF, but interactions predicting time to
      BF were observed for MSMB (rs10993994) and percentage of older single heads of
      households (P = 0.0004), and for HNF1B/TCF2 (rs4430796) and census tract per
      capita income (P = 0.0002). CONCLUSIONS: The context-specific macroenvironmental
      effects of genotype might improve the ability to identify groups that might
      experience poor prostate cancer outcomes. IMPACT: Risk estimation and clinical
      translation of genotype information might require an understanding of both
      individual- and macroenvironment-level context.

PMID- 20826829
TI  - Parental decision making about the HPV vaccine.
AB  - BACKGROUND: Prophylactic human papillomavirus (HPV) vaccines are available, but
      uptake is suboptimal. Information on factors influencing parental decisions
      regarding vaccination will facilitate the development of successful
      interventions. METHODS: Parents of girls ages 9 to 17 years (n = 476; cooperation
      rate = 67%) from a panel of U.S. households completed online surveys between
      September 2007 and January 2008, documenting vaccine knowledge, attitudes, and
      intentions. RESULTS: Among those aware of the vaccine, 19% had already vaccinated
      their daughter(s), 34% intended to, 24% were undecided, and 24% had decided
      against vaccination. Awareness of HPV was high but knowledge levels were
      suboptimal (mean 72%, SEM 0.8%). Black and Hispanic parents were significantly
      less likely to be aware of the vaccine compared with White parents. In
      multivariate analyses, compared with parents who opposed vaccination, those who
      had already vaccinated their daughter(s) or who intended to do so had more
      positive attitudes, reported fewer barriers, and were more likely to perceive
      that family and friends would endorse vaccination. They also reported higher
      levels of trust in pharmaceutical companies that produce the vaccine.
      CONCLUSIONS: Despite limited knowledge, most parents had decided to vaccinate
      their daughter(s). Given evidence of diminished access to information among Black
      and Hispanic parents, programs should focus on reaching these groups.
      Interventions should address parental concerns about behavioral consequences,
      reduce structural barriers, and promote the perception that vaccination is
      endorsed by significant others. Moreover, interventions may need to address
      mistrust of pharmaceutical companies. IMPACT STATEMENT: This study documents
      factors associated with parental decisions about HPV vaccination for their
      daughter(s) and provides direction for intervention development.

PMID- 20826830
TI  - Survival of women with colon cancer in relation to precancer anthropometric
      characteristics: the Iowa Women's Health Study.
AB  - BACKGROUND: We hypothesized that precancer anthropometric variables are
      associated with mortality among women who developed colon cancer in a prospective
      cohort, the Iowa Women's Health Study (IWHS). METHODS: From 1986 to 2005, 1,096
      incident cases of colon cancer were identified (mean age at diagnosis, 73 years).
      Anthropometric characteristics were self-measured before colon cancer diagnosis
      (in 1986). Cox proportional hazards regression was used to estimate hazard ratios
      (HR) and 95% confidence intervals (95% CI) for all-cause and colon-cancer
      mortality, adjusted for age at cancer diagnosis, stage, education, smoking
      status, and pack-years of smoking. RESULTS: During the follow-up of up to 20
      years, 493 women died; 289 had colon cancer as the underlying cause. The HRs of
      all-cause death were increased for the highest versus lowest tertile for weight
      (HR, 1.39; 95% CI, 1.10-1.76; P trend = 0.005); waist to hip ratio (WHR; HR,
      1.36; 95% CI, 1.08-1.72; P trend = 0.008), and waist (HR, 1.45; 95% CI, 1.15
      1.82; P trend = 0.001). Compared with that for body mass index (BMI) of 18.5 to
      24.9 kg/m(2), HRs were increased for BMI >or=30 kg/m(2) (HR, 1.45; 95% CI, 1.14
      1.85) and for the few women with BMI <18.5 kg/m(2) (HR, 1.89; 95% CI, 1.01-3.53).
      Colon cancer mortality was positively associated with WHR and waist: HR, 1.37
      (95% CI, 1.02;1.85; P trend = 0.04) and 1.34 (95% CI, 1.01-1.80; P trend = 0.05),
      respectively, for the highest versus lowest tertile. CONCLUSION: Greater
      precancer anthropometric measures and BMI <18.5 kg/m(2) predicted poorer survival
      among colon cancer patients. Higher abdominal adiposity measured by WHR and waist
      was associated with increased risk of colon cancer death. IMPACT: Prediagnostic
      obesity may be a modifiable risk factor for death in colon cancer patients.

PMID- 20826828
TI  - Missense variants in ATM in 26,101 breast cancer cases and 29,842 controls.
AB  - BACKGROUND: Truncating mutations in ATM have been shown to increase the risk of
      breast cancer but the effect of missense variants remains contentious. METHODS:
      We have genotyped five polymorphic (minor allele frequency, 0.9-2.6%) missense
      single nucleotide polymorphisms (SNP) in ATM (S49C, S707P, F858L, P1054R, and
      L1420F) in 26,101 breast cancer cases and 29,842 controls from 23 studies in the
      Breast Cancer Association Consortium. RESULTS: Combining the data from all five
      SNPs, the odds ratio (OR) was 1.05 for being a heterozygote for any of the SNPs
      and 1.51 for being a rare homozygote for any of the SNPs with an overall trend OR
      of 1.06 (P(trend) = 0.04). The trend OR among bilateral and familial cases was
      1.12 (95% confidence interval, 1.02-1.23; P(trend) = 0.02). CONCLUSIONS: In this
      large combined analysis, these five missense ATM SNPs were associated with a
      small increased risk of breast cancer, explaining an estimated 0.03% of the
      excess familial risk of breast cancer. IMPACT: Testing the combined effects of
      rare missense variants in known breast cancer genes in large collaborative
      studies should clarify their overall contribution to breast cancer
      susceptibility.

PMID- 20826831
TI  - The screening of volatile markers for hepatocellular carcinoma.
AB  - BACKGROUND: Breath analysis became promising for noninvasive diagnoses of cancer
      with sophisticated spectrometry technology introduced. This study aimed to screen
      volatile markers for hepatocellular carcinoma (HCC). METHODS: Breath samples were
      collected from 30 HCC patients who were comorbid with type B hepatitis and
      cirrhosis and from 27 hepatocirrhosis patients and 36 healthy persons, both taken
      as controls. The volatile organic compounds in the samples were analyzed with gas
      chromatography/mass spectrometry and the markers were selected by comparing their
      levels between groups. Each of the markers was evaluated by receiver operating
      characteristic (ROC) curves and a discriminant function using the markers was
      established. The relationships of alpha-fetoprotein (AFP) levels and clinical
      stages with the concentrations of the markers were also investigated. RESULTS: 3
      Hydroxy-2-butanone, styrene, and decane were screened as potential markers, among
      which 3-hydroxy-2-butanone was found to have the best diagnostic value. The
      diagnostic function using these markers had a sensitivity of 86.7% and a
      specificity of 91.7% between HCC patients and normal controls and a sensitivity
      of 83.3% and a specificity of 91.7% by cross-validation. No statistically
      significance (P > 0.05) was found for the concentration differences of these
      markers between HCC patients with AFP >400 or <400 microg/L or between stage I-II
      and stage III-IV patients. CONCLUSION: These volatile organic compounds could be
      useful as breath markers of HCC patients, independent of AFP levels or clinical
      stages. IMPACT: Breath analysis could be useful for early diagnosis of HCC,
      especially for AFP-negative HCC.

PMID- 20826832
TI  - Strategies for increasing mammography screening in primary care in Chile: results
      of a randomized clinical trial.
AB  - BACKGROUND: Breast cancer is the cancer with the highest incidence among women in
      Chile and in many Latin American countries. Breast cancer screening has very low
      compliance among Chilean women. METHODS: We compared the effects on mammography
      screening rates of standard care, of a low-intensity intervention based on mail
      contact, and of a high-intensity intervention based on mail plus telephone or
      personal contact. A random sample of 500 women with the age of 50 to 70 years
      registered at a community clinic in Santiago who had not had a mammogram in the
      past 2 years were randomly assigned to one of the three intervention groups. Six
      months after randomization, participants were re-evaluated for their compliance
      with mammography screening. The outcome was measured by self-report and by
      electronic clinical records. An intention to treat model was used to analyze the
      results. RESULTS: Between 92% and 93% of participants completed the study. Based
      on electronic records, mammography screening rates increased significantly from
      6% in the control group to 51.8% in the low-intensity group and 70.1% in the high
      intensity group. About 14% of participants in each group received opportunistic
      advice, 100% of participants in the low- and high-intensity groups received the
      mail contact, and 50% in the high-intensity group received a telephone or
      personal contact. CONCLUSION: A primary care intervention based on mail or brief
      personal contact could significantly improve mammogram screening rates. IMPACT: A
      relatively simple intervention could have a strong impact in breast cancer
      prevention in underserved communities.

PMID- 20826833
TI  - Metabolic factors and the risk of pancreatic cancer: a prospective analysis of
      almost 580,000 men and women in the Metabolic Syndrome and Cancer Project.
AB  - BACKGROUND: The aim of this study was to investigate the association between
      factors in metabolic syndrome (MetS; single and combined) and the risk of
      pancreatic cancer. METHODS: The Metabolic Syndrome and Cancer Project is a pooled
      cohort containing data on body mass index, blood pressure, and blood levels of
      glucose, cholesterol, and triglycerides. During follow-up, 862 individuals were
      diagnosed with pancreatic cancer. Cox proportional hazards analysis was used to
      calculate relative risks (RR) with 95% confidence intervals using the above
      mentioned factors categorized into quintiles and transformed into z-scores. All z
      scores were summarized and a second z-transformation creating a composite z-score
      for MetS was done. All risk estimates were calibrated to correct for a regression
      dilution bias. RESULTS: The trend over quintiles was positively associated with
      the risk of pancreatic cancer for mid-blood pressure (mid-BP) and glucose in men
      and for body mass index, mid-BP, and glucose in women. The z-score for the
      adjusted mid-BP (RR, 1.10; 1.01-1.20) and the calibrated z-score for glucose (RR,
      1.37; 1.14-1.34) were positively associated with pancreatic cancer in men. In
      women, a positive association was found for calibrated z-scores for mid-BP (RR,
      1.34; 1.08-1.66), for the calibrated z-score for glucose (RR, 1.98; 1.41-2.76),
      and for the composite z-score for MetS (RR, 1.58; 1.34-1.87). CONCLUSION: Our
      study adds further evidence to a possible link between abnormal glucose
      metabolism and risk of pancreatic cancer. IMPACT: To our knowledge, this is the
      first study on MetS and pancreatic cancer using prediagnostic measurements of the
      examined factors.

PMID- 20826834
TI  - Serum 25(OH) vitamin D and risk of breast cancer: a nested case-control study
      from the French E3N cohort.
AB  - BACKGROUND: High 25-hydroxyvitamin D [25(OH)D] serum concentrations have been
      found to be associated with reduced breast cancer risk. However, few studies have
      further investigated this relationship according to menopausal status, nor have
      they taken into account factors known to influence vitamin D status, such as
      dietary and serum calcium, parathyroid hormone, and estradiol serum levels.
      METHODS: We designed a nested case-control study within the French E3N cohort.
      Cases were women diagnosed with incident breast cancer (n = 636). Controls (n =
      1,272) were matched with cases on age, menopausal status at blood collection, age
      at menopause, and center and year of blood collection. Multivariate logistic
      regression models were established. RESULTS: We found a decreased risk of breast
      cancer with increasing 25(OH) vitamin D(3) serum concentrations (odds ratio,
      0.73; 95% confidence interval, 0.55-0.96; P trend = 0.02) among women in the
      highest tertile. We also observed a significant inverse association restricted to
      women under 53 years of age at blood sampling [odds ratio (T(3) versus T(1)),
      0.60; 95% confidence interval, 0.37-0.98; P trend = 0.04]. In premenopausal
      women, the risk was also decreased, although not significantly. CONCLUSION: Our
      findings support a decreased risk of breast cancer associated with high 25(OH)
      vitamin D(3) serum concentrations, especially in younger women, although we were
      unable to confirm a direct influence of age or menopausal status. IMPACT:
      Randomized intervention trials with vitamin D supplementation are required to
      confirm its benefits on breast cancer risk, but the maintenance of adequate
      vitamin D levels should be encouraged by public health policy.

PMID- 20826835
TI  - Seroprevalence of antibodies against human papillomavirus (HPV) types 16 and 18
      in four continents: the International Agency for Research on Cancer HPV
      Prevalence Surveys.
AB  - BACKGROUND: Few human papillomavirus (HPV) seroprevalence studies have been
      carried out in women from low-resource countries. METHODS: Seroprevalence of
      antibodies against HPV16 and HPV18 was assessed in 7,074 women >=15 years of age
      (median 44 years) from eight world areas. Serum antibodies against HPV16 and
      HPV18 were tested for using enzyme-linked immunosorbent assay. HPV DNA was
      assessed using a general primer GP5+/6+-mediated PCR. RESULTS: HPV16 and HPV18
      seroprevalence both ranged from <1% (Hanoi, Vietnam) to >or=25% (Nigeria). Of
      women who were HPV16 or HPV18 DNA-positive, seropositivity for the same type was
      39.8% and 23.2%, respectively. Seropositivity for either type was directly
      associated with markers of sexual behavior. HPV16 and/or 18 (HPV16/18)
      seropositive women had an increased risk of having cytologic abnormalities only
      if they were also HPV DNA-positive. A high international correlation was found
      between HPV16/18 seroprevalence and overall HPV DNA prevalence (r = 0.81; P =
      0.022). However, HPV16/18 seroprevalence was substantially higher than the
      corresponding DNA prevalence in all study areas (although to different extents)
      and, contrary to DNA, tended to increase from young to middle age, and then
      decline or remain fairly constant. In all study areas, the vast majority of the
      information on the burden of exposure to HPV16/18 derived from serology.
      CONCLUSIONS: The correlation between HPV DNA and HPV serology was not very good
      at an individual woman level, but high at a population level. IMPACT: HPV
      serology is a poor marker of current infection or related lesions, but it can
      contribute, together with DNA, in evaluating the variations in the burden of HPV
      infection worldwide.

PMID- 20826836
TI  - Prevalence of human papillomavirus types in high-grade cervical intraepithelial
      neoplasia and cancer in Italy.
AB  - BACKGROUND: The aim of this multicentric study was to identify human
      papillomavirus (HPV) type distribution in invasive cervical cancer and high-grade
      cervical intraepithelial neoplasia 2/3 (CIN2/3) in Italy. METHODS: Cases were
      sampled through the electronic databases at the pathology units of eight centers
      in six regions from central and southern Italy. HPV types were detected from
      paraffin-embedded tissue samples and cervical specimens through amplification of
      HPV DNA with GP5+/GP6+ primers, followed by genotyping with reverse line blot
      (RLB). Untyped HPV-positive samples were sequenced. HPV-negative samples
      underwent nested PCR, followed by either RLB or sequencing. Finally, the
      remaining HPV-negative samples were amplified with primers targeting the virus E6
      to E7 regions. RESULTS: From 1,162 cases initially selected, 722 samples were
      further analyzed: 144 CIN2, 385 CIN3, 157 invasive squamous carcinomas, and 36
      adenocarcinomas. Samples (6.9%) were HPV negative. The proportion of HPV16/18 was
      60.8%, 76.6%, and 78.8% in CIN2, CIN3, and invasive cancers, respectively (P
      trend = 0.004). There was a significant decreasing trend of HPV16/18 with age in
      invasive cancers, going from 92% in women <35 years to 73% in women >55 years (P
      = 0.036). The proportion of coinfections was 16.8%, 15.5%, and 10.0% in CIN2,
      CIN3, and invasive cancers, respectively (P trend = 0.07). CONCLUSIONS: The
      proportion of invasive cancers caused by HPV16/18 decreases with age at
      diagnosis. IMPACT: The absolute risk of an invasive cancer due to non-HPV16/18 in
      women under 35 is extremely low. This finding might prompt us to rise the age at
      which public HPV screening for vaccinated women should start.

PMID- 20826837
TI  - Rising melanoma incidence rates of the trunk among younger women in the United
      States.
AB  - BACKGROUND: Melanoma rates are rising among young women, possibly due to
      increasing UV radiation to previously protected body sites. Therefore, we
      examined melanoma incidence trends by age, gender, and body site. Descriptive
      methods were complemented with the age-period-cohort parameters net drift and
      longitudinal age trend. METHODS: Case and population data were obtained from the
      Surveillance, Epidemiology, and End Results (SEER) 9 Registries Database (1975
      2006). Net drift summarized the average annual percentage change in log-linear
      rates per year of calendar-time (or year of diagnosis). Longitudinal age trend
      summarized the average annual percentage change by attained age at diagnosis.
      Early- and late-onset melanomas have low and high longitudinal age trends,
      respectively. RESULTS: There were 105,829 melanomas diagnosed in the SEER 9
      Registries. The overall age-adjusted incidence rate (IR) for melanoma was
      17.7/100,000 person-years. Age-specific IRs were greater among women than men
      prior to age 40 years. Among women, IRs decreased for all anatomic sites relative
      to the trunk. The highest net drift occurred in truncal lesions among women (net
      drift, 3.8%/year of calendar time; 95% confidence interval, 3.5-4.0%). The lowest
      longitudinal age trends also were observed for truncal lesions among women
      (longitudinal age trend, 5.4%/year of attained age; 95% confidence interval, 5.1
      5.7). CONCLUSIONS: Although melanoma IRs overall have risen for decades, the
      combination of high net drift and low longitudinal age trend show that melanomas
      are rising preferentially on the trunk among young women. IMPACT: Future
      surveillance and analytic studies should consider melanoma effect modification by
      age, gender, and body site.

PMID- 20826838
TI  - Targeting a common collaborator in cancer development.
AB  - In this issue of Science Translational Medicine, Wallin et al. have identified a
      subset of breast and ovarian cancer cell lines that show synergistic response to
      the combination of doxorubicin and GDC-0941, a class IA phosphatidylinositol 3
      kinase (PI3K) inhibitor. Here, we discuss the potential implications of these
      data on the clinical development of PI3K pathway inhibitors as cancer
      therapeutics.

PMID- 20826839
TI  - Genome-wide association studies identify new targets in cardiovascular disease.
AB  - The prevalence of cardiovascular disease (CVD) continues to increase worldwide,
      highlighting the need for new therapeutic strategies. A recent meta-analysis of
      genome-wide association studies (GWASs) of over 100,000 individuals published in
      Nature identified 59 new loci associated with lipid traits; of these, a locus on
      chromosome 1p13 was most strongly associated with low-density lipoprotein
      cholesterol (LDL-C) levels. An accompanying study in Nature identified SORT1 as
      the causal gene at the 1p13 locus and showed that increased expression of
      sortilin-1 protein in liver was associated with lower LDL-C levels and a reduced
      risk of myocardial infarction. Together, these studies provide strong validation
      of the utility of GWASs in identifying biological pathways relevant to CVD
      pathogenesis and perhaps treatment.

PMID- 20826840
TI  - Integration of early physiological responses predicts later illness severity in
      preterm infants.
AB  - Physiological data are routinely recorded in intensive care, but their use for
      rapid assessment of illness severity or long-term morbidity prediction has been
      limited. We developed a physiological assessment score for preterm newborns, akin
      to an electronic Apgar score, based on standard signals recorded noninvasively on
      admission to a neonatal intensive care unit. We were able to accurately and
      reliably estimate the probability of an individual preterm infant's risk of
      severe morbidity on the basis of noninvasive measurements. This prediction
      algorithm was developed with electronically captured physiological time series
      data from the first 3 hours of life in preterm infants (< or =34 weeks gestation,
      birth weight < or =2000 g). Extraction and integration of the data with state-of
      the-art machine learning methods produced a probability score for illness
      severity, the PhysiScore. PhysiScore was validated on 138 infants with the leave
      one-out method to prospectively identify infants at risk of short- and long-term
      morbidity. PhysiScore provided higher accuracy prediction of overall morbidity
      (86% sensitive at 96% specificity) than other neonatal scoring systems, including
      the standard Apgar score. PhysiScore was particularly accurate at identifying
      infants with high morbidity related to specific complications (infection: 90% at
      100%; cardiopulmonary: 96% at 100%). Physiological parameters, particularly short
      term variability in respiratory and heart rates, contributed more to morbidity
      prediction than invasive laboratory studies. Our flexible methodology of
      individual risk prediction based on automated, rapid, noninvasive measurements
      can be easily applied to a range of prediction tasks to improve patient care and
      resource allocation.

PMID- 20826841
TI  - Nuclear phospho-Akt increase predicts synergy of PI3K inhibition and doxorubicin
      in breast and ovarian cancer.
AB  - The phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway is frequently
      disrupted in cancer and implicated in multiple aspects of tumor growth and
      survival. In addition, increased activity of this pathway in cancer is associated
      with resistance to chemotherapeutic agents. Therefore, it has been hypothesized
      that PI3K inhibitors could help to overcome resistance to chemotherapies. We used
      preclinical cancer models to determine the effects of combining the DNA-damaging
      drug doxorubicin with GDC-0941, a class I PI3K inhibitor that is currently being
      tested in early-stage clinical trials. We found that PI3K inhibition
      significantly increased apoptosis and enhanced the antitumor effects of
      doxorubicin in a defined set of breast and ovarian cancer models. Doxorubicin
      treatment caused an increase in the amount of nuclear phospho-Akt(Ser473) in
      cancer cells that rely on the PI3K pathway for survival. This increased phospho
      Akt(Ser473) response to doxorubicin correlates with the strength of GDC-0941's
      effect to augment doxorubicin action. These studies predict that clinical use of
      combination therapies with GDC-0941 in addition to DNA-damaging agents will be
      effective in tumors that rely on the PI3K pathway for survival.

PMID- 20826844
TI  - Cranial malformations in related white lions (Panthera leo krugeri).
AB  - White lions (Panthera leo krugeri) have never been common in the wild, and at
      present, the greatest population is kept in zoos where they are bred for
      biological and biodiversity conservation. During the years 2003 to 2008 in a
      zoological garden in northern Italy, 19 white lions were born to the same
      parents, who were in turn paternally consanguineous. Out of the 19 lions, 4 (21%)
      were stillborn, 13 (69%) died within 1 month, and 1 (5%) was euthanatized after 6
      months because of difficulty with prehension of food. Six lions (32%) showed
      malformations involving the head (jaw, tongue, throat, teeth, and cranial bones).
      One lion (5%) still alive at 30 months revealed an Arnold-Chiari malformation
      upon submission for neurological evaluation of postural and gait abnormalities.
      Paternal consanguinity of the parents, along with inbreeding among white lions in
      general, could account for the high incidence of congenital malformations of the
      head in this pride of white lions.

PMID- 20826843
TI  - Localization and functional characterization of pulmonary bovine odorant-binding
      protein.
AB  - Bovine odorant-binding protein (OBP) may function in olfaction and defense
      against oxidative injury, but its role in inflammation and defense against
      bacterial infection has not been investigated. Expression of OBP was discovered
      in the bovine lung and found to undergo changes in abundance during
      glucocorticoid administration and stress. OBP was localized to nasal, tracheal,
      and bronchial mucosal glands with immunohistochemistry, with faint expression in
      airway surface epithelium and none in bronchioles or alveoli. Two isoforms of OBP
      were identified, appearing to be differentially regulated during
      lipopolysaccharide-induced pulmonary inflammation, but differences between these
      isoforms were not revealed by matrix-assisted laser desorption/ionization-time of
      flight mass spectrometry. Functional studies showed no effect of OBP on in vitro
      growth of Escherichia coli or Mannheimia haemolytica under iron-replete or iron
      depleted conditions, nor did OBP opsonize bacteria for an enhanced neutrophil
      oxidative burst. However, OBP did reduce the ability of supernatants from
      lipopolysaccharide-stimulated macrophages to induce neutrophil chemotaxis. These
      findings indicate that OBP may inhibit neutrophil recruitment by inflammatory
      mediators, and they suggest an ability to bind macrophage-derived inflammatory
      mediators within the airways.

PMID- 20826845
TI  - Flow cytometry in veterinary oncology.
AB  - Flow cytometry is a highly sensitive and specific method for simultaneous
      analysis of multiple parameters of individual cells in a suspension. It has a
      range of applications in veterinary medicine, and it is increasingly used in
      veterinary oncology as more species-specific antibodies are generated and cross
      reactivity of antibodies is characterized. Two major applications in veterinary
      oncology are (1) immunophenotyping with a panel of fluorescently labeled
      antibodies to assess expression of cell markers and (2) determination of the DNA
      content of cells with fluorescent dyes that bind nucleic acids. The diagnostic
      and prognostic value of classifying round cell tumors of animals-especially,
      lymphocyte proliferations-remains to be fully determined, but studies to date
      have indicated benefit to patient management. Similarly, determining the
      proliferating fraction of tumors through DNA analysis remains to be standardized
      and validated in veterinary oncology but shows promise as an adjunct to
      morphologic tumor classification. This article reviews technical aspects of flow
      cytometry, availability of antibodies suitable for studies in domestic animals,
      and applications in veterinary oncology with emphasis on characterization of
      round cell tumors.

PMID- 20826846
TI  - Canine gastrointestinal stromal tumors: immunohistochemical expression of CD34
      and examination of prognostic indicators including proliferation markers Ki67 and
      AgNOR.
AB  - Gastrointestinal stromal tumors (GISTs), leiomyomas, and leiomyosarcomas are
      common mesenchymal neoplasms in the gastrointestinal (GI) tract of dogs. As
      previously diagnosed smooth muscle tumors of the canine GI tract are increasingly
      reclassified as GISTs, it becomes important to identify additional criteria that
      may assist in the diagnosis of these neoplasms, provide prognostic information,
      and offer targets for therapy. Examination of cluster of differentiation (CD),
      molecule expression (such as KIT [CD117] and CD34) as well as gross, histologic,
      and immunohistochemical features (such as tumor size, tumor location, mitotic
      index, AgNOR, and Ki67 labeling) in human GISTs has revealed new and valuable
      prognostic, diagnostic, and therapeutic information. In this study, GISTs were
      examined for the gross, histologic, and immunohistochemical features listed
      above. Forty-nine cases of canine gastrointestinal mesenchymal neoplasms from the
      Animal Medical Center (New York, NY) were categorized as GISTs (KIT positive),
      leiomyosarcoma/leiomyoma (KIT negative, smooth muscle actin [SMA], and/or desmin
      positive), or other (KIT, SMA, and desmin negative). A proportion (55%) of canine
      cases previously diagnosed as smooth muscle tumors were reclassified as GISTs
      according to KIT immunoreactivity. Statistical correlations with survival data
      were not possible because of insufficient follow-up data. However, there was a
      significant difference between mitotic index, AgNOR, and Ki67 scores depending on
      the location of the tumor (small vs large intestine). This study represents the
      first time CD34 immunoreactivity has been demonstrated in canine GISTs.

PMID- 20826847
TI  - Eight cases of feline cutaneous leishmaniasis in Texas.
AB  - Leishmaniasis is a zoonotic disease caused by intracellular Leishmania protozoa
      that are transmitted by sandflies. The disease occurs in 3 forms: cutaneous,
      mucocutaneous, and visceral. Cutaneous leishmaniasis has been reported in cats in
      Europe and South America and in 1 cat from Texas. Leishmania mexicana is endemic
      in Texas and has been reported to cause cutaneous lesions in humans. This article
      describes the pathology of 8 biopsy cases of feline cutaneous leishmaniasis
      presented to the Texas Veterinary Medical Diagnostic Laboratory over a 3.5-year
      period. The median age of the cats was 3 years; each was presented with nodular,
      ulcerative lesions on the pinnae and less commonly on the muzzle and periorbital
      skin. Histologically, the lesions were nodular to diffuse histiocytic dermatitis
      with numerous amastigotes (2-4 MUm) within macrophages and occasionally within
      the interstitium. Organisms were often contained within round, clear,
      intracellular vacuoles. In areas of necrosis, organisms were also free within the
      interstitium. The overlying epidermis was hyperkeratotic, hyperplastic, and often
      ulcerated. The organisms were not argyrophilic (Gomori methenamine silver),
      reacted poorly with periodic acid-Schiff reagent, and were inconsistently
      basophilic with Giemsa. Although not readily visible histologically, kinetoplasts
      were evident in amastigotes in cytologic preparations. The lesions were similar
      to those described for cutaneous L. mexicana infection in humans. In 5 of the 8
      cats, Leishmania mexicana DNA was amplified from paraffin-embedded tissue by
      polymerase chain reaction and sequenced.

PMID- 20826848
TI  - Clinical results and functional evaluation of the Chrisman-Snook procedure for
      lateral ankle instability in athletes.
AB  - There is no consensus regarding optimum surgical treatment for chronic ankle
      instability. The purpose of this study is to describe a variation of the Chrisman
      Snook lateral ligament reconstruction that the senior author uses in patients
      with chronic ankle instability recalcitrant to conservative management. All
      patients who underwent reconstruction from 1997 to 2006 were identified, and
      those with a minimum 2-year follow-up were included, representing a total of 44
      ankles in 43 patients. All underwent clinical evaluation and completion of the
      Foot and Ankle Outcome Survey and the Kaikkonen Scale. At mean follow-up of 4.4
      years, mean dorsiflexion loss was 2 degrees  compared with the nonoperative side.
      The postoperative mean Foot and Ankle Outcome Survey score was 74 +/- 16 (range,
      36-98), while the mean Kaikkonen total score was 77 +/- 14 (range, 40-95). Thirty
      eight patients (84.6%) were satisfied with their result. Six patients (13.6%)
      underwent reoperation, including 4 with peroneal tendon scarring requiring
      tenolysis. Return to sport was achieved in 28 of 35 patients (80%) at a median of
      6 months postoperatively. It is concluded that dorsiflexion loss can be minimized
      and return to sport expected in most patients following this variation of the
      Chrisman-Snook reconstruction.

PMID- 20826849
TI  - Conceptualizing schizophrenia through attenuated symptoms in the population.

PMID- 20826850
TI  - Neuroimaging the infant: the application of modern neurobiological methods to the
      neurodevelopmental hypothesis of schizophrenia.

PMID- 20826851
TI  - Asthma, suicide risk, and psychiatric comorbidity.

PMID- 20826852
TI  - Food additives and behavior: first genetic insights.

PMID- 20826853
TI  - Personality disorders in DSM-5.

PMID- 20826854
TI  - Identification and treatment of a pineal region tumor in an adolescent with
      prodromal psychotic symptoms.
AB  - An adolescent male patient originally presented to a prodromal clinical research
      program with severe obsessive-compulsive behaviors and subthreshold symptoms of
      psychosis, which eventually developed into first-rank psychotic symptoms. The
      patient was followed over a 2-year period. His symptoms did not respond to
      psychotherapy or pharmacotherapy. However, when a pineal region tumor was
      discovered and treated with chemotherapy and autologous stem cell rescue, both
      psychotic symptoms and psychosocial functioning reverted toward baseline.
      Although subcortical brain structures have been implicated in the pathophysiology
      of idiopathic psychosis, reports of psychiatric sequelae of treatment of
      subcortical tumors are rare. Etiological pathways that may have played a role in
      symptom development are of particular interest, as understanding these mechanisms
      may shed light on the pathophysiology of psychotic disorders more generally.

PMID- 20826855
TI  - Images in psychiatry. Haiti earthquake psychiatric relief.

PMID- 20826857
TI  - Brain SPECT imaging in clinical practice.

PMID- 20826858
TI  - Integrating pharmaceutical-supported research evidence in residency training.

PMID- 20826859
TI  - Electroconvulsive therapy for catatonia.

PMID- 20826861
TI  - Trainees and collaborations with industry.

PMID- 20826862
TI  - Medication guesses in double-blind studies.

PMID- 20826864
TI  - Mania in a patient with H1N1: is oseltamivir the culprit or a red herring?

PMID- 20826867
TI  - HIV, syphilis, hepatitis C and risk behaviours among commercial sex male clients
      in Sichuan province, China.
AB  - OBJECTIVES: Commercial sex male clients (CSMC) are at risk of sexually
      transmitted infections (STI) including HIV. This study reports the prevalence of
      HIV, syphilis and hepatitis C virus (HCV), a history of STI and HIV-related risk
      behaviours in a sample of 600 CSMC in three urban areas in Sichuan province,
      China. The risk factors for prevalent syphilis infection are also examined.
      METHODS: A cross-sectional survey was conducted with 600 CSMC in Sichuan
      province, China. Finger stick blood samples were collected for HIV, syphilis and
      HCV tests. Risk factors for syphilis were assessed using multivariate logistic
      regression by accounting for variance within and between study sites. RESULTS:
      Western blot confirmatory test results indicated that HIV prevalence was 1.5%
      (n=9). 32 participants (5.3%) screened positive for syphilis and 52 (8.7%)
      positive for HCV. The overall prevalence of consistent condom use with female sex
      workers (FSW) was 30.5%. Multivariate logistic regression analyses revealed local
      household registration (AOR 0.35, 95% CI 0.25 to 0.50), having snorted heroin in
      the past 6&emsp14;months (AOR 2.36, 95% CI 1.18 to 4.74), always washing genitals
      after having sex with FSW (AOR 3.04, 95% CI 1.10 to 9.12) and consistent condom
      use with FSW (AOR 0.67, 95% CI 0.46 to 0.98) were significant correlates of
      syphilis infection. CONCLUSIONS: There is a large burden of syphilis infection
      coupled with high-risk sexual and substance use behaviours among male clients in
      Sichuan province, China. The data suggest that effective and comprehensive
      prevention interventions to promote condom use and reduce substance use among
      male clients in Sichuan province are urgently needed.

PMID- 20826868
TI  - Why do patients want information if not to take part in decision making?
AB  - There is empirical evidence that many patients want information about treatment
      options even though they do not want to take a full part in decision-making about
      treatment. Such evidence may have considerable ethical implications but is
      methodologically problematic. It is argued here that, in fact, it is not at all
      surprising that patients' informational interests should be separable from (and
      often stronger than) their interests in decision-making. A number of different
      reasons for wanting information are offered, some to do with the content of
      information; some with the process, others with the fact or occasion of
      informing. This philosophical clarification leads to some suggestions for further
      empirical study.

PMID- 20826869
TI  - Ethical issues related to computerised family medical histories in sickle cell
      disease: Inforare.
AB  - The Inforare project aims to set up a system for the sharing of clinical and
      familial data, in order to study how genes are related to the severity of sickle
      cell disease. While the computerisation of clinical records represents a valuable
      research goal, an ethical framework is necessary to guarantee patients'
      protection and their rights in this developing field. Issues relating to patient
      information during the Inforare study were analysed by the steering committee.
      Several major concerns were discussed by the committee and formalized in the
      patients' information letter: educating patients to aid the recruitment of family
      members, rules of confidentiality and the disclosure of aggregate, individual and
      unexpected research results. This paper presents the main issues addressed.

PMID- 20826871
TI  - Neurological picture. Primary multiple calvarial hydatid cysts--a rare
      occurrence.

PMID- 20826870
TI  - Clinical and functional outcome and factors predicting prognosis in osmotic
      demyelination syndrome (central pontine and/or extrapontine myelinolysis) in 25
      patients.
AB  - AIMS: To assess the functional and clinical outcome in a sizeable cohort of
      patients with osmotic demyelination syndrome (ODS) and to characterise the
      factors which could predict the final outcome. METHODS: Twenty five consecutive
      patients with ODS formed the study cohort. The diagnosis of ODS was based on
      clinical features with corroborating imaging findings. Two functional scales-
      Functional Independent Measure (FIM) and Disability Rating Scale (DRS)--were
      applied to assess the functional status at the time of admission, discharge and
      last follow-up. Patients who became independent for activities of daily living
      (ADL) at last follow-up were classified as favourable outcome, and those who died
      or became dependent for ADL were classified as a poor outcome group respectively.
      The Fisher exact test and Mann-Whitney U test were used to assess categorical and
      continuous variables respectively. RESULTS: The mean age at diagnosis was 53 +/-
      14 years. Five (20%) had central pontine myelinolysis, seven (28%) had
      extrapontine myelinolysis, and 13 (52%) had both. Hyponatraemia and hypokalaemia
      were noted in 20 (80%) and 10 (40%) patients respectively. Six (24%) received
      intravenous methylprednisolone. Eleven (46%) had a favourable outcome at a mean
      follow-up of 2.2 +/- 2.5 years. Hyponatraemia <= 115 mEq (p=0.04), associated
      hypokalaemia (p=0.04) and low Glasgow Coma Scale (GCS) (p=0.008) at presentation
      were predictive of poor outcome. The mean FIM score at admission (p=0.05) and at
      discharge (p=0.01), and mean DRS at admission (p=0.05) were predictive of poor
      outcome. CONCLUSIONS: Higher GCS scores, better scores in functional scales in
      hospital, less severe hyponatraemia and absence of superadded hypokalaemia
      predicted favourable outcome.

PMID- 20826872
TI  - Efficacy of physiotherapy interventions late after stroke: a meta-analysis.
AB  - OBJECTIVE: Physiotherapy is usually provided only in the first few months after
      stroke, while its effectiveness and appropriateness in the chronic phase are
      uncertain. The authors conducted a systematic review and meta-analysis of
      randomised clinical trials (RCT) to evaluate the efficacy of physiotherapy
      interventions on motor and functional outcomes late after stroke. METHODS: The
      authors searched published studies where participants were randomised to an
      active physiotherapy intervention, compared with placebo or no intervention, at
      least 6 months after stroke. The outcome was a change in mobility and activities
      of daily living (ADL) independence. The quality of the trials was evaluated using
      the PEDro scale. Findings were summarised across studies as effect size (ES) or,
      whenever possible, weighted mean difference (WMD) with 95% CI in random effects
      models. RESULTS: Fifteen RCT were included, enrolling 700 participants with
      follow-up data. The meta-analysis of primary outcomes from the original studies
      showed a significant effect of the intervention (ES 0.29, 95% CI 0.14 to 0.45).
      The efficacy of the intervention was particularly evident when short- and long
      distance walking were considered as separate outcomes, with WMD of 0.05 m/s (95%
      CI 0.008 to 0.088) and 20 m (95% CI 3.6 to 36.0), respectively. Also, ADL
      improvement was greater, though non-significantly, in the intervention group. No
      significant heterogeneity was found. INTERPRETATION: A variety of physiotherapy
      interventions improve functional outcomes, even when applied late after stroke.
      These findings challenge the concept of a plateau in functional recovery of
      patients who had experienced stroke and should be valued in planning community
      rehabilitation services.

PMID- 20826873
TI  - Early central atrophy rate predicts 5 year clinical outcome in multiple
      sclerosis.
AB  - OBJECTIVE: To examine the predictive value of central atrophy in early multiple
      sclerosis (MS) patients, for medium term clinical outcome. METHODS: In 54
      patients with recently diagnosed MS, clinical and MRI parameters were obtained at
      baseline, and after 2 and 5.5 years of follow-up. In addition to conventional MRI
      parameters and the annualised percentage brain volume change (aPBVC), the
      annualised percentage ventricular volume change (aPVVC) was quantified. Main
      outcome measure was disease progression, defined by an increase in Expanded
      Disability Status Scale of >=1 after 5.5 years. RESULTS: Disease progression
      occurred in 29 patients. aPVVC within the first two years was significantly
      higher in these progressing patients (median 4.76%; IQR 3.05-9.17) compared with
      stable patients (median 3.23%; IQR -0.1-6.02) (p=0.02). A logistic regression
      model selected aPVVC within the first 2 years as the only MRI marker predicting
      progression after 5.5 years (OR 1.17, 95% CI 1.02 to 1.35). When entering all MRI
      and clinical markers, again aPVVC within the first 2 years was the only MRI
      marker selected. While aPVVC was correlated between the two consecutive time
      intervals (rho=0.41, p<0.01), aPBVC was not. Furthermore, baseline T2 lesion load
      and gadolinium enhancing lesion load were correlated with aPVVC in the second
      time interval (2-5.5 years) but not with aPBVC. CONCLUSION: The rate of
      ventricular enlargement seems to be even more strongly predictive of disease
      progression after medium term follow-up than whole brain atrophy rate, and also
      outperforms lesion measures. Central atrophy rate could therefore be an important
      prognostic marker, especially in the early stages of MS.

PMID- 20826874
TI  - Tasmania: state of MS in Australia.

PMID- 20826875
TI  - Cortical and frontal atrophy are associated with cognitive impairment in age
      related confluent white-matter lesion.
AB  - OBJECTIVE: Although age-related confluent white-matter lesion (WML) is an
      important substrate for cognitive impairment, the mechanisms whereby WML induces
      cognitive impairment are uncertain. The authors investigated cognitive predictors
      in patients with confluent WML. METHODS: Among 100 patients with ischaemic stroke
      with confluent WML on MRI, the authors assessed executive function and global
      cognition by the Mattis Dementia Rating Scale--Initiation/Perseveration Subscale
      (MDRS I/P) and Mini-Mental State Examination (MMSE), respectively. All volumetric
      measures were corrected for intracranial volume. The authors investigated the
      association between basic demography, vascular risk factors, APOE status, WML
      volume, infarct measures (volume, number, location), microbleed number, atrophy
      measures (global, central, regional) and cognitive performance. The authors also
      performed Pittsburgh Compound B (PIB) imaging among seven cognitive impaired
      patients with stroke. RESULTS: WML was no longer related to cognitive performance
      after adding atrophy into regression equations. Multivariate regression models
      showed that cortical grey matter volume independently accounted for performance
      on both the MDRS I/P (beta=0.241, p=0.045) and MMSE (beta=0.243, p=0.032). Models
      examining frontal subregions revealed that volumes of both left (beta=0.424,
      p<0.001) and right (beta=0.219, p=0.045) lateral frontal orbital gyri predicted
      MDRS I/P, whereas education (beta=0.385, p<0.001) and left lateral frontal
      orbital gyrus (beta=0.222, p=0.037) predicted MMSE. Volumes of WML and
      cognitively relevant brain regions were significantly associated. Seven patients
      with PIB imaging showed no uptake pattern typical of Alzheimer's disease,
      suggesting a predominantly vascular aetiology for the cognitive impairment and
      brain changes in these patients. CONCLUSIONS: Cognitive impairment in patients
      with confluent WML is mediated by global and frontal cortical atrophy.

PMID- 20826876
TI  - A case of systemic brucellosis with spondylodiscitis mimicking postoperative
      spondylodiscitis after lumbar disc surgery.

PMID- 20826877
TI  - Hippocampal morphometry in population-based incident Alzheimer's disease and
      vascular dementia: the HAAS.
AB  - BACKGROUND: Hippocampal changes may be a useful biomarker for Alzheimer's disease
      if they are specific to dementia sub-type. We compare hippocampal volume and
      shape in population-based incident cases of Alzheimer's disease and vascular
      dementia (VaD). METHODS: Participants are Japanese-American men from the Honolulu
      Asia Aging Study. The following analysis is based on a sub-group of men with mild
      incident Alzheimer's disease (n=24: age=82.5 +/- 4.6) or incident VaD (n=14:
      age=80.5 +/- 4.5). To estimate hippocampal volume, one reader, blinded to
      dementia diagnosis, manually outlined the left and right formation of the
      hippocampus using published criteria. We used 3-D mapping methods developed at
      the Laboratory of Neuro Imaging (LONI) to compare regional variation in
      hippocampal width between dementia groups. RESULTS: Hippocampal volume was about
      5% smaller in the Alzheimer's disease group compared to the VaD group, but the
      difference was not significant. Hippocampal shape differed between the two case
      groups for the left (p<0.04) but not right (p<0.21) hippocampus. The specific
      region of the hippocampus that most consistently differed between the Alzheimer's
      disease and VaD cases was in the lateral portion of the left hippocampus. Our
      interpretation of this region is that it intersects the CA1 sub-region to a great
      extent but also includes the dentate gyrus (and hilar region) and subiculum.
      CONCLUSION: As indicated by shape analysis, there are some differences in atrophy
      localisation between the Alzheimer's disease and VaD cases, despite the finding
      that volume of the hippocampi did not differ. These findings suggest hippocampal
      atrophy in Alzheimer's disease may be more focal than in VaD.

PMID- 20826878
TI  - Home telemonitoring of non-invasive ventilation decreases healthcare utilisation
      in a prospective controlled trial of patients with amyotrophic lateral sclerosis.
AB  - BACKGROUND: Non-invasive ventilation (NIV) is an efficient method for treating
      respiratory failure in patients with amyotrophic lateral sclerosis (ALS).
      However, it requires a process of adaptation not always achieved due to poor
      compliance. The role of telemonitoring of NIV is not yet established. OBJECTIVES:
      To test the advantage of using modem communication in NIV of ALS patients.
      DESIGN: Prospective, single blinded controlled trial. Population and methods
      According to their residence, 40 consecutive ventilated ALS patients were
      assigned to one of two groups: a control group (G1, n=20) in which compliance and
      ventilator parameter settings were assessed during office visits; or an
      intervention group (G2, n=20) in which patients received a modem device connected
      to the ventilator. The number of office and emergency room visits and hospital
      admissions during the entire span of NIV use and the number of parameter setting
      changes to achieve full compliance were the primary outcome measurements.
      RESULTS: Demographic and clinical features were similar between the two groups at
      admission. No difference in compliance was found between the groups. The
      incidence of changes in parameter settings throughout the survival period with
      NIV was lower in G2 (p<0.0001) but it was increased during the initial period
      needed to achieve full compliance. The number of office or emergency room visits
      and inhospital admissions was significantly lower in G2 (p<0.0001). Survival
      showed a trend favouring G2 (p=0.13). CONCLUSIONS: This study shows that
      telemonitoring reduces health care utilisation with probable favourable
      implications on costs, survival and functional status.

PMID- 20826880
TI  - Fixed point characterization of biological networks with complex graph topology.
AB  - MOTIVATION: Feedback circuits are important motifs in biological networks and
      part of virtually all regulation processes that are needed for a reliable
      functioning of the cell. Mathematically, feedback is connected to complex
      behavior of the systems, which is often related to bifurcations of fixed points.
      Therefore, several approaches for the investigation of fixed points in biological
      networks have been developed in recent years. Many of them assume the fixed point
      coordinates to be known, and an efficient way to calculate the entire set of
      fixed points for interrelated feedback structures is highly desirable. RESULTS:
      In this article, we consider regulatory network models, which are differential
      equations with an underlying directed graph that illustrates independencies among
      variables. We introduce the circuit-breaking algorithm (CBA), a method that
      constructs one-dimensional characteristics for these network models, which
      inherit important information about the system. In particular, fixed points are
      related to the zeros of these characteristics. The CBA operates on the graph
      topology, and results from graph theory are used in order to make calculations
      efficient. Our framework provides a general scheme for analyzing network models
      in terms of interrelated feedback circuits. The efficiency of the approach is
      demonstrated on a model for calcium oscillations based on experiments in
      hepatocytes, which consists of several interrelated feedback circuits.

PMID- 20826879
TI  - A novel method for similarity analysis and protein sub-cellular localization
      prediction.
AB  - MOTIVATION: Biological sequence was regarded as an important study by many
      biologists, because the sequence contains a large number of biological
      information, what is helpful for scientists' studies on biological cells, DNA and
      proteins. Currently, many researchers used the method based on protein sequences
      in function classification, sub-cellular location, structure and functional site
      prediction, including some machine-learning methods. The purpose of this article,
      is to find a new way of sequence analysis, but more simple and effective.
      RESULTS: According to the nature of 64 genetic codes, we propose a simple and
      intuitive 2D graphical expression of protein sequences. And based on this
      expression we give a new Euclidean-distance method to compute the distance of
      different sequences for the analysis of sequence similarity. This approach
      contains more sequence information. A typical phylogenetic tree constructed based
      on this method proved the effectiveness of our approach. Finally, we use this
      sequence-similarity-analysis method to predict protein sub-cellular localization,
      in the two datasets commonly used. The results show that the method is
      reasonable.

PMID- 20826881
TI  - Robust and accurate data enrichment statistics via distribution function of sum
      of weights.
AB  - MOTIVATION: Term-enrichment analysis facilitates biological interpretation by
      assigning to experimentally/computationally obtained data annotation associated
      with terms from controlled vocabularies. This process usually involves obtaining
      statistical significance for each vocabulary term and using the most significant
      terms to describe a given set of biological entities, often associated with
      weights. Many existing enrichment methods require selections of (arbitrary number
      of) the most significant entities and/or do not account for weights of entities.
      Others either mandate extensive simulations to obtain statistics or assume normal
      weight distribution. In addition, most methods have difficulty assigning correct
      statistical significance to terms with few entities. RESULTS: Implementing the
      well-known Lugananni-Rice formula, we have developed a novel approach, called
      SaddleSum, that is free from all the aforementioned constraints and evaluated it
      against several existing methods. With entity weights properly taken into
      account, SaddleSum is internally consistent and stable with respect to the choice
      of number of most significant entities selected. Making few assumptions on the
      input data, the proposed method is universal and can thus be applied to areas
      beyond analysis of microarrays. Employing asymptotic approximation, SaddleSum
      provides a term-size-dependent score distribution function that gives rise to
      accurate statistical significance even for terms with few entities. As a
      consequence, SaddleSum enables researchers to place confidence in its
      significance assignments to small terms that are often biologically most
      specific. AVAILABILITY: Our implementation, which uses Bonferroni correction to
      account for multiple hypotheses testing, is available at
      http://www.ncbi.nlm.nih.gov/CBBresearch/qmbp/mn/enrich/. Source code for the
      standalone version can be downloaded from
      ftp://ftp.ncbi.nlm.nih.gov/pub/qmbpmn/SaddleSum/.

PMID- 20826882
TI  - Meniscal repair for radial tears of the midbody of the lateral meniscus.
AB  - BACKGROUND: Radial meniscal tears historically have been treated by partial
      meniscectomy, although they are more biomechanically detrimental than
      longitudinal tears. Clinical results after meniscal repair for radial tears of
      the midbody of the lateral meniscus have been reported rarely. STUDY DESIGN: 
      CASE SERIES: Level of evidence, 4. METHODS: Fourteen consecutive patients who had
      radial tears of the midbody of the lateral meniscus underwent arthroscopic
      repair. Inclusion criteria were radial tears involving the red-red or red-white
      zone. All patients underwent all-inside meniscal repair using absorbable sutures.
      Postoperative evaluation was performed using joint-line tenderness, McMurray
      test, range of motion, and follow-up magnetic resonance imaging (MRI) scan at 6
      months postoperatively. Lysholm knee score and Tegner activity level were
      evaluated at last follow-up. In 4 patients, second-look arthroscopies were
      performed. RESULTS: The average follow-up was 36.3 months. No patient had joint
      line tenderness. Three patients complained of pain or a click on McMurray test.
      The mean follow-up range of motion was 138.6 degrees . Follow-up MRI scans
      demonstrated that 5 (35.7%) menisci were healed, 8 (57.1%) were partially healed,
      and 1 (7.1%) was not healed. The follow-up Lysholm score was 94.7 (range, 81-100;
      standard deviation [SD] = 6.4) and Tegner score was 5.7 (range, 3-7; SD = 1.4).
      Second-look arthroscopies in 4 patients showed partial healing of meniscal tears.
      CONCLUSION: Meniscal repair for radial tears of the midbody of the lateral
      meniscus may be an effective, alternative treatment to partial meniscectomy.

PMID- 20826884
TI  - The rat acute-phase protein alpha2-macroglobulin plays a central role in
      amifostine-mediated radioprotection.
AB  - Previously we reported that elevated circulating concentrations of the acute
      phase (AP) protein alpha(2)-macroglobulin (alpha(2)M), either as typically
      occurring in pregnant female rats or after administration to male rats, provides
      radioprotection, displayed as 100% survival of experimental animals exposed to
      total-body irradiation with 6.7 Gy (LD(50/30)) x-rays, that is as effective as
      that afforded by the synthetic radioprotector amifostine. The finding that
      amifostine administration induces a 45-fold increase in alpha(2)M in the
      circulation led us to hypothesise that alpha(2)M assumes an essential role in
      both natural and amifostine-mediated radioprotection in the rat. In the present
      work we examined the activation of cytoprotective mechanisms in rat hepatocytes
      after the exogenous administration of alpha(2)M and amifostine. Our results
      showed that the IL6/JAK/STAT3 hepatoprotective signal pathway, described in a
      variety of liver-injury models, upregulated the alpha(2)M gene in amifostine
      pretreated animals. In both alpha(2)M- and amifostine-pretreated rats we observed
      the activation of the Akt signalling pathways that mediate cellular survival. At
      the cellular level this was reflected as a significant reduction of irradiation
      induced DNA damage that allowed for the rapid and complete restoration of liver
      mass and ultimately at the level of the whole organism the complete restoration
      of body weight. We conclude that the selective upregulation of alpha(2)M plays a
      central role in amifostine-provided radioprotection.

PMID- 20826883
TI  - ROTUNDIFOLIA4 regulates cell proliferation along the body axis in Arabidopsis
      shoot.
AB  - Molecular genetics has been successful in identifying leaf- size regulators such
      as transcription factors, phytohormones, and signal molecules. Among them, a
      ROTUNDIFOLIA4-LIKE/DEVIL (RTFL/DVL) family of Arabidopsis, genes encoding
      peptides with no secretion-signal sequence, is unique in that their
      overexpressors have a reduced number of leaf cells specifically along the
      proximodistal axis. However, because the RTFL/DVL lack any obvious homology with
      functionally identified domains, and because of genetic redundancy among
      RTFL/DVL, their molecular and developmental roles are unclear. In this study we
      focused on one member in the family, ROTUNDIFOLIA4 (ROT4), and identified the
      core functional region within it and we found no proteolytic processing in
      planta. Developmental analysis of leaf primordia revealed that ROT4
      overexpression reduces the meristematic zone size within the leaf blade.
      Moreover, induced local overexpression demonstrated that ROT4 acts as a regulator
      of the leaf shape via a change in positional cue along the longitudinal axis.
      Similarly, ROT4 overexpression results in a protrusion of the main inflorescence
      stem, again indicating a change in positional cue along the longitudinal axis.
      These results suggest that ROT4 affects the positional cue and cell proliferation
      along the body axis.

PMID- 20826885
TI  - A survey of the optical hazards associated with hospital light sources with
      reference to the Control of Artificial Optical Radiation at Work Regulations
      2010.
AB  - Workplace exposure to coherent and incoherent optical radiation from artificial
      sources is regulated under the Artificial Optical Radiation Directive (AORD)
      2006/25/EC, now implemented in the UK under the Control of Artificial Optical
      Radiation at Work Regulations (AOR) 2010. These regulations set out exposure
      limit values. Implementing the AOR (2010 Health and Safety Statutory Instrument
      No 1140 www.legislation.gov.uk/uksi/2010/1140/pdf/uksi_20101140_en.pdf)
      requirements in a hospital environment is a potentially complex problem because
      of the wide variety of sources used for illumination, diagnosis and therapy. A
      survey of sources of incoherent optical radiation in a large hospital is reported
      here. The survey covers examples of office lighting, operating theatre lighting,
      examination lamps, and sources for ultraviolet phototherapy and visible
      phototherapies, including photodynamic therapy and neonatal blue-light therapy.
      The results of the survey are used to inform consideration of the strategy that a
      hospital might reasonably adopt both to demonstrate compliance with the AOR
      (2010) and to direct implementation effort.

PMID- 20826886
TI  - Measurement of thoron gas in the environment using a Lucas scintillation cell.
AB  - A simple and fast method for measuring the concentration of (220)Rn in the
      environment was developed based on the AB-5 portable radon measuring device.
      First, background counts were measured with a Lucas scintillation cell (LSC),
      then air sampling measurement was started immediately and lasted for 1 min; the
      (220)Rn concentration could be calculated from the counts before and after
      sampling as well as the theoretical detection efficiency. Results of theoretical
      calculations showed that in a pure (220)Rn environment the lower detection limit
      of the LSC would be some 65  Bq m(-3) (with a confidence level of 70%). The
      experimental results showed that compared with a RAD7 monitor in pure (220)Rn or
      mixed (222)Rn/(220)Rn environments the deviations were less than +/- 10%. This
      method can also be used for quantitative measurement of (220)Rn concentration.

PMID- 20826887
TI  - Modelling particle retention in the alveolar-interstitial region of the human
      lungs.
AB  - Better information is available now on long-term particle retention in the human
      lungs than there was in 1994, when the human respiratory tract model (HRTM) was
      adopted by the International Commission on Radiological Protection (ICRP). Three
      recent studies are especially useful because they provide such information for
      groups of people who inhaled very similar aerosols. For all three the HRTM
      significantly underestimates lung retention of insoluble material. The purpose of
      this work was to improve the modelling of long-term retention in the deep lung. A
      simple physiologically based model developed to predict lung and lymph node
      particle retention in coal miners was found to represent lung retention in these
      studies adequately. Instead of the three alveolar-interstitial (AI) compartments
      in the HRTM, it has an alveolar compartment which clears to the bronchial tree
      and to a second compartment, representing the interstitium, which clears only to
      lymph nodes. The main difference from the HRTM AI model is that a significant
      fraction of the AI deposit is sequestered in the interstitium. To obtain default
      parameter values for general use, the model was fitted to data from the three
      recent studies, and also the experimental data used in development of the HRTM to
      define particle transport from the AI region for the first year after intake. The
      result of the analysis is that about 40% of the AI deposit of insoluble particles
      is sequestered in the interstitium and the remaining fraction is cleared to the
      ciliated airways with a half-time of about 300 days. For some long-lived
      radionuclides in relatively insoluble form (type S), this increased retention
      increases the lung dose per unit intake by 50-100% compared to the HRTM value.

PMID- 20826889
TI  - Radiological implications of the use of uranium in vaseline glass.
AB  - Uranium oxides have been used as colourants in glassware since the 19th century
      and this type of glass is commonly referred to as vaseline glass. There are many
      collectors of vaseline glass in the UK who obtain pieces from the UK antiques
      market or from abroad. Dose rate measurements were made for a number of items of
      vaseline glass, and the uranium content of one item was measured. Potential doses
      to collectors were considered, along with implications for trade and transport
      due to the uranium content of the glassware. It was concluded that generally
      items of vaseline glass could give rise to low skin doses from beta radiation,
      though frequent wearing of necklaces made from vaseline glass may lead to doses
      in excess of the HPA (Health Protection Agency) dose criterion for consumer
      products that are not related to safety. Registration under the Radioactive
      Substances Act will not be required and almost all items of vaseline glass should
      be suitable for sending through the Royal Mail. For those items not accepted by
      Royal Mail, it is understood that the transport regulations for radioactive
      materials would not apply.

PMID- 20826890
TI  - Short-lived variations in the background gamma-radiation dose.
AB  - Sudden increases in the background gamma-radiation dose may occur due to the
      removal of (222)Rn and (220)Rn progeny from the atmosphere by wet deposition
      mechanisms. This contribution has been measured using a Geiger-Muller detector at
      the Atomic Weapons Establishment (Aldermaston, UK) during July 2005-April 2006.
      The results are approximated by a log-normal distribution and there were nine
      separate occurrences of the gamma-radiation dose exceeding 125% of the geometric
      mean value. The increases were associated with periods of heavy rainfall,
      although no correlation was evident between the dose rate and the amount of
      rainfall, as increased rainfall dilutes the activity further rather than
      increasing its atmospheric removal. The events were preceded by periods of fine
      weather and atmospheric stability that allow for the build-up of (222)Rn and
      (220)Rn progeny. Similar increases in gamma-radiation dose have been measured at
      a nearby monitoring station situated approximately 11 miles from Aldermaston.
      Increases in gamma-radiation dose during heavy rainfall have also been observed
      throughout the UK, that followed the trajectory of an air mass. All events
      decreased to typical values within 1-2 h as the water permeated into the ground
      below and the radioactivity decayed away.

PMID- 20826891
TI  - The ambient dose equivalent at flight altitudes: a fit to a large set of data
      using a Bayesian approach.
AB  - The problem of finding a simple, generally applicable description of worldwide
      measured ambient dose equivalent rates at aviation altitudes between 8 and 12 km
      is difficult to solve due to the large variety of functional forms and
      parametrisations that are possible. We present an approach that uses Bayesian
      statistics and Monte Carlo methods to fit mathematical models to a large set of
      data and to compare the different models. About 2500 data points measured in the
      periods 1997-1999 and 2003-2006 were used. Since the data cover wide ranges of
      barometric altitude, vertical cut-off rigidity and phases in the solar cycle 23,
      we developed functions which depend on these three variables. Whereas the
      dependence on the vertical cut-off rigidity is described by an exponential, the
      dependences on barometric altitude and solar activity may be approximated by
      linear functions in the ranges under consideration. Therefore, a simple Taylor
      expansion was used to define different models and to investigate the relevance of
      the different expansion coefficients. With the method presented here, it is
      possible to obtain probability distributions for each expansion coefficient and
      thus to extract reliable uncertainties even for the dose rate evaluated. The
      resulting function agrees well with new measurements made at fixed geographic
      positions and during long haul flights covering a wide range of latitudes.

PMID- 20826892
TI  - Patient skin dose measurements during coronary interventional procedures using
      Gafchromic film.
AB  - Interventional cardiology (IC) procedures are known to give high radiation doses
      to patients and cardiologists as they involve long fluoroscopy times and several
      cine runs. Patients' dose measurements were carried out at the cardiology
      department in a local hospital in Penang, Malaysia, using Gafchromic XR-RV2
      films. The dosimetric properties of the Gafchromic film were first characterised.
      The film was energy and dose rate independent but dose dependent for the
      clinically used values. The film had reproducibility within +/- 3% when
      irradiated on three different days and hence the same XR-RV2 dose-response
      calibration curve can be used to obtain patient entrance skin dose on different
      days. The increase in the response of the film post-irradiation was less than 4%
      over a period of 35 days. For patient dose measurements, the films were placed on
      the table underneath the patient for an under-couch tube position. This study
      included a total of 44 patients. Values of 35-2442 mGy for peak skin dose (PSD)
      and 10.9-344.4 Gy cm(2) for dose-area product (DAP) were obtained. DAP was found
      to be a poor indicator of PSD for PTCA procedures but there was a better
      correlation (R(2) = 0.7344) for CA + PTCA procedures. The highest PSD value in
      this study exceeded the threshold dose value of 2 Gy for early transient skin
      injury recommended by the Food and Drug Administration.

PMID- 20826893
TI  - Natural radioactivities in iron and nickel ores imported into Japan and the dose
      assessment for workers handling them.
AB  - Japan imports Fe and Ni ores from abroad for use as industrial raw materials in
      the manufacture of industrial products like stainless steel. Some of these ores
      might contain high levels of radioactivity, and then workers handling them would
      be exposed to radiation without being aware of it. Activity concentrations in
      these ores should be measured to evaluate the radiation exposure of workers. In
      this study, Fe and Ni ores used as industrial raw materials were collected from
      iron and steel companies, and the activity concentrations of the (238)U series,
      the (232)Th series and (40)K in these ores were determined using inductively
      coupled plasma mass spectrometry (ICP-MS) and gamma ray spectrometry. The
      activity concentrations of the (238)U series, the (232)Th series and (40)K in
      these ores samples were lower than the International Atomic Energy Agency (IAEA)
      values. The doses to workers handling these ores were estimated using methods for
      dose assessment given in a report by the European Commission. In each scenario, a
      maximum value of the annual effective dose to workers was estimated to be about
      6.8 * 10(-6) Sv, which was lower than intervention exemption levels (annual dose
      1.0 * 10(-3) Sv) given in International Commission on Radiological Protection
      (ICRP) Publication 82.

PMID- 20826894
TI  - The birth of UNSCEAR--the midwife's tale.
AB  - The creation in 1955 of the United Nations Scientific Committee on the Effects of
      Atomic Radiation (UNSCEAR) was driven by the potential dangers of worldwide
      radioactive fall-out from the testing of nuclear bombs: both a cold war political
      issue and a complex radiological problem. Sir Raymond Appleyard was Secretary of
      the UNSCEAR Committee from 1956 to 1961, linking the Committee and its
      delegations with the UN as host institution and with the other members of the
      Committee's scientific staff. The present reflections are his purely personal
      views and memories of incidents and people during the Committee's formative
      years. They complement Dr David Sowby's earlier recollections (Sowby 2008 J.
      Radiol. Prot. 28 271-6).

PMID- 20826895
TI  - Analysis of shielding calculation methods for 16- and 64-slice computed
      tomography facilities.
AB  - The new multislice computed tomography (CT) machines require some new methods of
      shielding calculation, which need to be analysed. NCRP Report No. 147 proposes
      three shielding calculation methods based on the following dosimetric parameters:
      weighted CT dose index for the peripheral axis (CTDI(w, per)), dose-length
      product (DLP) and isodose maps. A survey of these three methods has been carried
      out. For this analysis, we have used measured values of the dosimetric quantities
      involved and also those provided by the manufacturer, making a comparison between
      the results obtained. The barrier thicknesses when setting up two different
      multislice CT instruments, a Philips Brilliance 16 or a Philips Brilliance 64, in
      the same room, are also compared. Shielding calculation from isodose maps
      provides more reliable results than the other two methods, since it is the only
      method that takes the actual scattered radiation distribution into account. It is
      concluded therefore that the most suitable method for calculating the barrier
      thicknesses of the CT facility is the one based on isodose maps. This study also
      shows that for different multislice CT machines the barrier thicknesses do not
      necessarily become bigger as the number of slices increases, because of the great
      dependence on technique used in CT protocols for different anatomical regions.

PMID- 20826896
TI  - Monitoring of radon gas in caves of the Yorkshire Dales, United Kingdom.
AB  - A number of vocational training courses are held in caves in the Yorkshire Dales
      region of the United Kingdom. The instructors and students involved in these
      courses have the potential to be exposed to enhanced levels of radon ((222)Rn)
      and its progeny as a result of their occupations. A prior radiological risk
      assessment for the training courses recommended that an environmental monitoring
      programme be carried out to establish the radon concentrations in the caves, and
      that the caving instructors wear personal radon dosemeters. Radon gas
      concentrations varied seasonally, being at their highest in summer and their
      lowest in winter. The lowest result was 40  Bq m(-3) recorded in Lower Longchurn
      cave during winter, whilst the highest result was 4440  Bq m(-3) recorded in
      Crackpot cave during the summer. As the individuals involved in the caving are
      entering atmospheres with radon gas concentrations in excess of 400  Bq m(-3),
      the Ionising Radiation Regulations 1999 (GB Parliament 2000 Ionising Radiations
      Regulations 1999 (London: Stationary Office) SI 1999/3232) apply. A system of
      work is therefore in place to control exposure to radon. This system of work
      stipulates an initial dose investigation level of 1 mSv, a second dose
      investigation level of 2 mSv and an annual dose limit of 6 mSv. The highest
      annual dose recorded to date is 2.2 mSv, although the average (median) annual
      dose is only 0.5 mSv.

PMID- 20826897
TI  - An instrument for measuring the unattached fraction of radon progeny with etched
      track detectors.
AB  - To measure the unattached fraction of radon progeny, a new type of portable, low
      cost, reusable integrating monitor with etched track detector (CR-39) was
      developed. This monitor simultaneously gives the average equilibrium-equivalent
      concentrations of unattached (222)Rn progeny (EEC(Rn)(u)), attached (222)Rn
      progeny (EEC(Rn)(a)) and also (220)Rn progeny (EEC(Tn)). It was calculated,
      according to the detection efficiencies which were derived by the Monte Carlo
      method, that the lower detection limits for EEC(Rn)(u), EEC(Rn)(a) and EEC(Tn)
      are 0.03  Bq m(-3), 0.12  Bq m(-3) and 0.07 Bq m(-3), respectively for 24 h
      integrating sampling at a flow rate of 2.92  l min(-1). The validity of the new
      monitor was confirmed through a series of intercomparison experiments.

PMID- 20826898
TI  - The biological effectiveness of targeted radionuclide therapy based on a whole
      body pharmacokinetic model.
AB  - Biologically effective dose (BED) may be more of a relevant quantity than
      absorbed dose for establishing tumour response relationships. By taking into
      account the dose rate and tissue-specific parameters such as repair and
      radiosensitivity, it is possible to compare the relative biological effects of
      different targeted radionuclide therapy (TRT) agents. The aim of this work was to
      develop an analytical tumour BED calculation for TRT that could predict a
      relative biological effect based on normal body and tumour pharmacokinetics. This
      work represents a step in the direction of establishing relative pharmacokinetic
      criteria of when the BED formalism is more applicable than absorbed dose for TRT.
      A previously established pharmacokinetic (PK) model for TRT was used and adapted
      into the BED formalism. An analytical equation for the protraction factor, which
      incorporates dose rate and repair rate, was derived. Dose rates within the normal
      body and tumour were related to the slopes of their time-activity curves which
      were determined by the ratios of their respective PK parameters. The
      relationships between the tumour influx-to-efflux ratio (k(34):k(43)), central
      compartment efflux-to-influx ratio (k(12):k(21)), central elimination (k(el)),
      and tumour repair rate (MU), and tumour BED were investigated. As the k(34):k(43)
      ratio increases and the k(12):k(21) ratio decreases, the difference between
      tumour BED and D increases. In contrast, as the k(34):k(43) ratios decrease and
      the k(12):k(21) ratios increase, the tumour BED approaches D. At large
      k(34):k(43) ratios, the difference between tumour BED and D increases to a
      maximum as k(el) increases. At small k(34):k(43) ratios, the tumour BED
      approaches D at very small k(el). At small MU and small k(34):k(43) ratios, the
      tumour BED approaches D. For large k(34):k(43) ratios, large MU values cause
      tumour BED to approach D. This work represents a step in the direction of
      establishing relative PK criteria of when the BED formalism is more applicable
      than absorbed dose for TRT. It also provides a framework by which the biological
      effects of different TRT agents can be compared in order to predict efficacy.

PMID- 20826900
TI  - Numerical model of heat transfer in the human eye with consideration of fluid
      dynamics of the aqueous humour.
AB  - In this work we present a new 3D numerical model for heat transfer in the human
      eye, which takes into account the aqueous humour flow in the anterior chamber. We
      show that consideration of this phenomenon in the calculations alters the
      temperature distribution on the corneal and lens surfaces, without, however,
      noticeably changing their absolute values. The most notable effect is that the
      coolest area of the cornea moves at a point of 2 mm inferior to its geometric
      centre. The maximum velocity of the fluid in the anterior chamber was found to be
      3.36 * 10(-4) m s(-1). The effect of the flow on displacing the cool area of the
      corneal surface temperature is counterbalanced by assuming anisotropic thermal
      conductivity. The model was implemented in the case of an artificial intraocular
      lens to show the resulting temperature variations.

PMID- 20826899
TI  - On the potential of a new IVUS elasticity modulus imaging approach for detecting
      vulnerable atherosclerotic coronary plaques: in vitro vessel phantom study.
AB  - Peak cap stress amplitude is recognized as a good indicator of vulnerable plaque
      (VP) rupture. However, such stress evaluation strongly relies on a precise, but
      still lacking, knowledge of the mechanical properties exhibited by the plaque
      components. As a first response to this limitation, our group recently developed,
      in a previous theoretical study, an original approach, called iMOD (imaging
      modulography), which reconstructs elasticity maps (or modulograms) of atheroma
      plaques from the estimation of strain fields. In the present in vitro
      experimental study, conducted on polyvinyl alcohol cryogel arterial phantoms, we
      investigate the benefit of coupling the iMOD procedure with the acquisition of
      intravascular ultrasound (IVUS) measurements for detection of VP. Our results
      show that the combined iMOD-IVUS strategy: (1) successfully detected and
      quantified soft inclusion contours with high positive predictive and sensitivity
      values of 89.7 +/- 3.9% and 81.5 +/- 8.8%, respectively, (2) estimated reasonably
      cap thicknesses larger than ~300 um, but underestimated thinner caps, and (3)
      quantified satisfactorily Young's modulus of hard medium (mean value of 109.7 +/-
      23.7 kPa instead of 145.4 +/- 31.8 kPa), but overestimated the stiffness of soft
      inclusions (mean Young's moduli of 31.4 +/- 9.7 kPa instead of 17.6 +/- 3.4 kPa).
      All together, these results demonstrate a promising benefit of the new iMOD-IVUS
      clinical imaging method for in vivo VP detection.

PMID- 20826901
TI  - CT reconstruction from portal images acquired during volumetric-modulated arc
      therapy.
AB  - Volumetric-modulated arc therapy (VMAT), a form of intensity-modulated arc
      therapy (IMAT), has become a topic of research and clinical activity in recent
      years. As a form of arc therapy, portal images acquired during the treatment
      fraction form a (partial) Radon transform of the patient. We show that these
      portal images, when used in a modified global cone-beam filtered backprojection
      (FBP) algorithm, allow a surprisingly recognizable CT-volume to be reconstructed.
      The possibility of distinguishing anatomy in such VMAT-CT reconstructions
      suggests that this could prove to be a valuable treatment position-verification
      tool. Further, some potential for local-tomography techniques to improve image
      quality is shown.

PMID- 20826902
TI  - Quantitative accuracy of the closed-form least-squares solution for targeted
      SPECT.
AB  - The aim of this study is to investigate the quantitative accuracy of the closed
      form least-squares solution (LSS) for single photon emission computed tomography
      (SPECT). The main limitation for employing this method in actual clinical
      reconstructions is the computational cost related to operations with a large
      sized system matrix. However, in some clinical situations, the size of the system
      matrix can be decreased using targeted reconstruction. For example, some oncology
      SPECT studies are characterized by intense tracer uptakes that are localized in
      relatively small areas, while the remaining parts of the patient body have only a
      low activity background. Conventional procedures reconstruct the activity
      distribution in the whole object, which leads to relatively poor image
      accuracy/resolution for tumors while computer resources are wasted, trying to
      rebuild diagnostically useless background. In this study, we apply a concept of
      targeted reconstruction to SPECT phantom experiments imitating such oncology
      scans. Our approach includes two major components: (i) disconnection of the
      entire imaging system of equations and extraction of only those parts that
      correspond to the targets, i.e., regions of interest (ROI) encompassing active
      containers/tumors and (ii) generation of the closed-form LSS for each target ROI.
      We compared these ROI-based LSS with those reconstructed by the conventional MLEM
      approach. The analysis of the five processed cases from two phantom experiments
      demonstrated that the LSS approach outperformed MLEM in terms of the noise level
      inside ROI. On the other hand, MLEM better recovered total activity if the number
      of iterations was large enough. For the experiment without background activity,
      the ROI-based LSS led to noticeably better spatial activity distribution inside
      ROI. However, the distributions pertaining to both approaches were practically
      identical for the experiment with the concentration ratio 7:1 between the
      containers and the background.

PMID- 20826903
TI  - Fractionation effects in particle radiotherapy: implications for hypo
      fractionation regimes.
AB  - The aim is to demonstrate the potential impact of changes in the value of the
      beta parameter in the linear quadratic (LQ) model on the calculation of clinical
      relative biological effectiveness (RBE) values used for high linear energy
      transfer (LET) radiotherapy. The parameter RBE(min) is introduced into the LQ
      formulation to account for possible changes in the beta radiosensitivity
      coefficient with changing LET. The model is used to fit fractionated data under
      two conditions, where RBE(min) = 1 and RBE(min) ? 1. Nonlinear regression and
      analysis of variance are used to test the hypothesis that the inclusion of a non
      unity value of RBE(min) better predicts the total iso-effective dose required at
      low number of fractions for fast neutrons, carbon ions, pi-meson and proton
      fractionation data obtained for various tissues from previous publications. For
      neutrons the assumption of RBE(min) ? 1 provided a better fit in 89% of the
      cases, whereas for carbon ions RBE(min) ? 1 provided a better fit only for normal
      tissue at the spread-out Bragg peak. The results provide evidence of the impact
      that variations in the beta parameter may have when calculating clinically
      relevant RBE values, especially when using high doses per fraction (i.e.
      hypofractionation) of high-LET radiations.

PMID- 20826904
TI  - Experimental validation of a commercial 3D dose verification system for intensity
      modulated arc therapies.
AB  - We validate the dosimetric performance of COMPASS(r), a novel 3D quality
      assurance system for verification of volumetric-modulated arc therapy (VMAT)
      treatment plans that can correlate the delivered dose to the patient's anatomy,
      taking into account the tissue inhomogeneity. The accuracy of treatment delivery
      was assessed by the COMPASS(r) for 12 VMAT plans, and the resulting assessments
      were evaluated using an ionization chamber and film measurements. Dose-volume
      relationships were evaluated by the COMPASS(r) for three additional treatment
      plans and these were used to verify the accuracy of treatment planning dose
      calculations. The results matched well between COMPASS(r) and measurements for
      the ionization chamber (<=3%) and film (73-99% for gamma((3%/3 mm)) < 1 and 98
      100% for gamma((5%/5 mm)) < 1) for the phantom plans. Differences in dose-volume
      statistics for the average dose to the PTV were within 2.5% for three treatment
      plans. For the structures located in the low-dose region, a maximum difference of
      <9% was observed. In its current implementation, the system could measure the
      delivered dose with sufficient accuracy and could project the 3D dose
      distribution directly on the patient's anatomy. Slight deviations were found for
      large open fields. These could be minimized by improving the COMPASS(r) in-built
      beam model.

PMID- 20826906
TI  - An automated four-point scale scoring of segmental wall motion in
      echocardiography using quantified parametric images.
AB  - The aim of this paper is to develop an automated method which operates on
      echocardiographic dynamic loops for classifying the left ventricular regional
      wall motion (RWM) in a four-point scale. A non-selected group of 37 patients (2
      and 4 chamber views) was studied. Each view was segmented according to the
      standardized segmentation using three manually positioned anatomical landmarks
      (the apex and the angles of the mitral annulus). The segmented data were analyzed
      by two independent experienced echocardiographists and the consensual RWM scores
      were used as a reference for comparisons. A fast and automatic parametric imaging
      method was used to compute and display as static color-coded parametric images
      both temporal and motion information contained in left ventricular dynamic
      echocardiograms. The amplitude and time parametric images were provided to a
      cardiologist for visual analysis of RWM and used for RWM quantification. A cross
      validation method was applied to the segmental quantitative indices for
      classifying RWM in a four-point scale. A total of 518 segments were analyzed.
      Comparison between visual interpretation of parametric images and the reference
      reading resulted in an absolute agreement (Aa) of 66% and a relative agreement
      (Ra) of 96% and kappa (kappa) coefficient of 0.61. Comparison of the automated
      RWM scoring against the same reference provided Aa = 64%, Ra = 96% and kappa =
      0.64 on the validation subset. Finally, linear regression analysis between the
      global quantitative index and global reference scores as well as ejection
      fraction resulted in correlations of 0.85 and 0.79. A new automated four-point
      scale scoring of RWM was developed and tested in a non-selected database. Its
      comparison against a consensual visual reading of dynamic echocardiograms showed
      its ability to classify RWM abnormalities.

PMID- 20826905
TI  - Pediatric dosimetry for intrapleural lung injections of (32)P chromic phosphate.
AB  - Intracavitary injections of (32)P chromic phosphate are used in the therapy of
      pleuropulmonary blastoma and pulmonary sarcomas in children. The lung dose,
      however, has never been calculated despite the potential risk of lung toxicity
      from treatment. In this work the dosimetry has been calculated in target tissue
      and lung for pediatric phantoms. Pleural cavities were modeled in the Monte Carlo
      code MCNP within the pediatric MIRD phantoms. Both the depth-dose curves in the
      pleural lining and into the lung as well as 3D dose distributions were calculated
      for either homogeneous or inhomogeneous (32)P activity distributions. Dose-volume
      histograms for the lung tissue and isodose graphs were generated. The results for
      the 2D depth-dose curve to the pleural lining and tumor around the pleural cavity
      correspond well with the point kernel model-based recommendations. With a 2 mm
      thick pleural lining, one-third of the lung parenchyma volume gets a dose more
      than 30 Gy (V(30)) for 340 MBq (32)P in a 10 year old. This is close to lung
      tolerance. Younger children will receive a larger dose to the lung when the lung
      density remains equal to the adult value; the V(30) relative lung volume for a 5
      year old is 35% at an activity of 256 MBq and for a 1 year old 165 MBq yields a
      V(30) of 43%. At higher densities of the lung tissue V(30) stays below 32%. All
      activities yield a therapeutic dose of at least 225 Gy in the pleural lining.
      With a more normal pleural lining thickness (0.5 mm instead of 2 mm) the injected
      activities will have to be reduced by a factor 5 to obtain tolerable lung doses
      in pediatric patients. Previous dosimetry recommendations for the adult apply
      well down to lung surface areas of 400 cm(2). Monte Carlo dosimetry quantitates
      the three-dimensional dose distribution, providing a better insight into the
      maximum tolerable activity for this therapy.

PMID- 20826907
TI  - Time course of fibronectin in the peri-implant tissue and neointima formation
      after functional implantation of polyester-based vascular prostheses with
      different porosity in pigs.
AB  - Intima hyperplasia, resulting from extracellular matrix (ECM) secretion, can lead
      to vascular prosthesis occlusion and is a major problem in vascular surgery.
      Fibronectin might contribute to ongoing ECM secretion. However, the exact role of
      fibronectin and its influence on neointima formation remains unclear. This study
      was aimed at investigating the time course of the fibronectin area fraction and
      neointima formation following the functional implantation of three different
      polyester vascular prostheses into pigs. The infrarenal aorta from 15 animals (n
      = 5/group) was replaced by prosthesis segments with low, medium and high primary
      porosity. After 7, 14, 21, 28 and 116 days, the prostheses were morphometrically
      examined. Overall, the fibronectin area fraction was inversely correlated with
      the neointima thickness, demonstrating high fibronectin levels in the early phase
      (days 7 and 14) and low levels in the later phase with almost complete neointima
      formation (days 21-116). Throughout the study, fibronectin levels were highest at
      the proximal anastomosis region. The low porosity prosthesis had the highest
      fibronectin area fraction and a delayed neointima formation in the middle phase
      (days 21 and 28) but the highest neointima lining on day 116. The results
      indicate a relationship between fibronectin and neointima formation with the
      prosthesis porosity, demonstrating the importance of the textile design for
      tissue reactions following implantation.

PMID- 20826908
TI  - Preparation and characterization of chitosan-heparin composite matrices for blood
      contacting tissue engineering.
AB  - Chitosan has been widely used for biomaterial scaffolds in tissue engineering
      because of its good mechanical properties and cytocompatibility. However, the
      poor blood compatibility of chitosan has greatly limited its biomedical
      utilization, especially for blood contacting tissue engineering. In this study,
      we exploited a polymer blending procedure to heparinize the chitosan material
      under simple and mild conditions to improve its antithrombogenic property. By an
      optimized procedure, a macroscopically homogeneous chitosan-heparin (Chi-Hep)
      blended suspension was obtained, with which Chi-Hep composite films and porous
      scaffolds were fabricated. X-ray photoelectron spectroscopy and sulfur elemental
      analysis confirmed the successful immobilization of heparin in the composite
      matrices (i.e. films and porous scaffolds). Toluidine blue staining indicated
      that heparin was distributed homogeneously in the composite matrices. Only a
      small amount of heparin was released from the matrices during incubation in
      normal saline for 10 days. The composite matrices showed improved blood
      compatibility, as well as good mechanical properties and endothelial cell
      compatibility. These results suggest that the Chi-Hep composite matrices are
      promising candidates for blood contacting tissue engineering.

PMID- 20826909
TI  - Longitudinal acoustic properties of poly(lactic acid) and poly(lactic-co-glycolic
      acid).
AB  - Acoustics offers rich possibilities for characterizing and monitoring the
      biopolymer structures being employed in the field of biomedical engineering. Here
      we explore the rudimentary acoustic properties of two common biodegradable
      polymers: poly(lactic acid) and poly(lactic-co-glycolic acid). A pulse-echo
      technique is developed to reveal the bulk speed of sound, acoustic impedance and
      acoustic attenuation of small samples of the polymer across a pertinent
      temperature range of 0-70  degrees C. The glass transition appears markedly as
      both a discontinuity in the first derivative of the speed of sound and a sharp
      increase in the acoustic attenuation. We further extend our analysis to consider
      the role of ethanol, whose presence is observed to dramatically modify the
      acoustic properties and reduce the glass transition temperature of the polymers.
      Our results highlight the sensitivity of acoustic properties to a range of bulk
      properties, including visco-elasticity, molecular weight, co-polymer ratio,
      crystallinity and the presence of plasticizers.

PMID- 20826910
TI  - Different effects of implanting vascular bundles and sensory nerve tracts on the
      expression of neuropeptide receptors in tissue-engineered bone in vivo.
AB  - We investigated whether implantation of vascular bundles or sensory nerves
      affected the expression of calcitonin gene-related peptide type I receptor
      (CGRP1R) and neuropeptide Y1 receptor (NPY1R) in tissue-engineered bone. We
      implanted osteogenically induced bone marrow mesenchymal stem cells (BMSCs) with
      beta-tricalcium phosphate (beta-TCP) as the scaffold material either with sensory
      nerve tracts (group I, n = 18), vascular bundles (group II, n = 18) or alone
      (group III, n = 18) to repair a 1.2 cm femur defect in the rabbit. Better
      osteogenesis was observed by x-ray and histology in groups I and II than in group
      III at 4, 8 and 12 weeks. Within the new bone, the mRNA levels of the two
      neuropeptide receptors determined by real-time PCR increased through week 8, and
      then gradually decreased (P < 0.05). Expression of the neuropeptide receptors
      determined by immunohistochemistry was lowest at 4 weeks (P < 0.05) and was
      higher in group II than in group I (P < 0.05). Expression was significantly
      higher in groups I and II than in group III at all time points. We conclude that
      implanting vascular bundles into tissue-engineered bone can significantly improve
      the early expression of CGRP1R and NPY1R. In contrast, implantation of sensory
      nerves did not show the same dramatic effect as implantation of vascular bundles.

PMID- 20826911
TI  - Use of synovium-derived stromal cells and chitosan/collagen type I scaffolds for
      cartilage tissue engineering.
AB  - The objective was to investigate synovium-derived stromal cells (SDSCs) coupled
      with chitosan/collagen type I (CS/COL-I) scaffolds for cartilage engineering.
      CS/COL-I scaffolds were fabricated through freeze-drying and cross-linked by 1
      ethyl-3-(3-dimethylaminopropyl)carbodiimide. SDSCs were isolated from synovium
      and cultured onto CS/COL-I scaffolds, constructs of which were incubated in serum
      free chondrogenic medium with sequential application of TGF-beta1 and bFGF for up
      to 21 days and then implanted into nude mice. The physical characteristics of the
      scaffolds were examined. The quality of the in vitro constructs was assessed in
      terms of DNA content by PicoGreen assay and cartilaginous matrix by histological
      examination. The implants of the constructs were evaluated by histological and
      immunohistochemical examinations and reverse transcription PCR. Results indicated
      that the CS/COL-I scaffold showed porous structures, and the DNA content of SDSCs
      in CS/COL-I scaffolds increased at 1 week culture time. Both of the constructs in
      vitro and the implants were examined with positive stained GAGs histologically
      and the implants with positive collagen type II immunohistochemically. RT-PCR of
      the implants indicated that aggrecan and collagen type II expressed. It suggested
      that SDSCs coupled with CS/COL-I scaffolds treated sequentially with TGF-beta1
      and bFGF in vitro were highly competent for engineered cartilage formation in
      vitro and in vivo.

PMID- 20826912
TI  - Genetic and epidemiological risk factors in the development of bronchopulmonary
      dysplasia.
AB  - Bronchopulmonary dysplasia (BPD) is the chronic lung disease of preterm infants
      and still represents a major burden of prematurity. Several clinical risk factors
      for the onset of the disease are already known. In addition, some candidate genes
      have recently been identified. We set out to determine clinical as well as
      genetic risk factors for the development of BPD in the German population. 155
      infants born with a gestational age < or = 28 at the tertiary neonatal Centre,
      Freiburg, were recruited. Clinical data were recorded from hospital charts. 47
      children developed moderate or severe BPD. For genetic analyses, 37 polymorphisms
      within sixteen genes were genotyped on all children. The strongest
      epidemiological risk factor for BPD was birth weight, followed by low gestational
      age. Genetic association was detected with single polymorphisms within Tumour
      necrosis factor alpha, Toll like receptor 10 and vascular endothelial growth
      factor. The former two genes showed also association with BPD in haplotype
      analyses. In conclusion, association of BPD was far more convincingly found with
      a few clinical factors than with genetic polymorphisms. This underscores the
      genetic complexity of the disease. Furthermore, the identification of
      predisposing genetic polymorphisms might be hampered by the complex interaction
      between clinical and genetic factors.

PMID- 20826913
TI  - Peptides in low molecular weight fraction of serum associated with hepatocellular
      carcinoma.
AB  - The incidence of hepatocellular carcinoma (HCC) in the United States is
      increasing and the increase is projected to continue for several decades. The
      overall survival of HCC patients is poor and treatments are not effective in part
      because most of the diagnoses come at a late stage. The development of new
      markers for detection of HCC would significantly improve patient prognosis. This
      paper describes identification of candidate markers previously reported in our
      serologic study of an Egyptian population by quantitative comparison of matrix
      assisted laser desorption ionization time of flight (MALDI-TOF) mass spectra. To
      identify these marker candidates, we performed LC-MS/MS sequencing that
      identified nine native peptides associated with HCC, including two reported
      previously. Four truncations of N terminus of complement C3f and a fibrinopeptide
      increased in control sera; two complement C4alpha peptides, a zyxin peptide, and
      a coagulation factor XIII peptide increased in cancer patient sera. We have also
      identified increased biliverdin diglucuronide in the sera of cancer patients.
      These peptides could potentially serve as markers of HCC following additional
      validation studies; however, association of similar peptides with other diseases
      and cancers dictates a very cautious approach.

PMID- 20826914
TI  - 14-3-3 sigma and p53 expression in gastric cancer and its clinical applications.
AB  - 14-3-3 sigma (sigma) induces G2 arrest enabling the repair of damaged DNA. The
      function of 14-3-3 sigma is frequently lost in tumor cells, indicating a
      potential tumor suppressor function. The purpose of this study was to evaluate
      the prognostic value of 14-3-3 sigma expression in human gastric cancer. 14-3-3
      sigma expression was analyzed by immunohistochemistry in 157 tumor samples of
      patients, who underwent resection for gastric cancer. Since 14-3-3 sigma is
      involved in the p53 network, p53 expression was detected in parallel and
      correlated with 14-3-3 sigma. 14-3-3 sigma was found to be overexpressed in 75
      (47.8%) of 157 cases, the overexpression rate of p53 protein was 27.4%. 14-3-3
      sigma overexpression was statistically significantly associated with pT-stage
      (p=0.041) pN-stage (p=0.015) and UICC-stage (p=0.019) and showed a borderline
      significance with Lauren classification (p=0.057). Univariate survival
      calculations revealed a coexistent 14-3-3 sigma and p53 overexpression as a
      significant predictor of disease-free survival. Multivariate analysis did not
      unfold 14-3-3 as an independent prognostic factor for disease-free survival and
      overall survival. Concomitant 14-3-3 sigma and p53 overexpression in tumor cells
      of patients with gastric cancer identifies a population of patients with
      relatively unfavorable prognosis.

PMID- 20826915
TI  - Plasma protein oxidation and its correlation with antioxidant potential during
      human aging.
AB  - Previous studies have indicated that the main molecular characteristic of aging
      is the progressive accumulation of oxidative damages in cellular macromolecules.
      Proteins are one of the main molecular targets of age-related oxidative stress,
      which have been observed during aging process in cellular systems.. Reactive
      oxygen species (ROS) can lead to oxidation of amino acid side chains, formation
      of protein-protein cross-linkages, and oxidation of the peptide backbones. In the
      present study, we report the age-dependent oxidative alterations in biomarkers of
      plasma protein oxidation: protein carbonyls (PCO), advanced oxidation protein
      products (AOPPs) and plasma total thiol groups (T-SH) in the Indian population
      and also correlate these parameters with total plasma antioxidant potential. We
      show an age dependent decrease in T-SH levels and increase in PCO and AOPPs
      level. The alterations in the levels of these parameters correlated significantly
      with the total antioxidant capacity of the plasma. The levels of oxidized
      proteins in plasma provide an excellent biomarker of oxidative stress due to the
      relative long half-life of such oxidized proteins.

PMID- 20826916
TI  - Bladder cancer risk associated with genotypic polymorphism of the matrix
      metalloproteinase-1 and 7 in North Indian population.
AB  - Matrix metalloproteinases (MMPs) contribute to tumor invasion and
      microenvironment, hence are associated with bladder cancer risk. We therefore,
      tested whether polymorphisms in MMP genes modify the risk of bladder cancer (BC)
      and whether smoke exposure modifies this risk. Genotyping was performed in 200 BC
      patients and 200 controls by polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP). MMP1-1607 2G/2G and MMP7-181 GG genotype were
      associated with increased risk of BC (p < 0.001; OR, 3.04; 95% CI- 1.71-5.39 and
      p, 0.005; OR, 2.38; 95% CI- 1.30-4.34) respectively. Smokers in BC patients
      showed significant increased risk for the same SNPs (p, 0.006; OR, 3.20; 95% CI-
      1.40-7.31 and p, 0.009; OR, 2.85; 95% CI- 1.30-6.23 respectively). Haplotype
      analysis too revealed significant association with G/2G of MMP1-519-1607 (p<
      0.001; OR, 2.62; 95% CI- 1.68-4.09). The 2G allele carrier (1G/2G + 2G/2G) of
      MMP1-1607 showed a protective effect and high recurrence free survival in
      Bacillus Calmette-Guerin (BCG) treated non muscle invasive BC (NMIBC) patients
      (log rank p, 0.030). Our data suggested that MMP1-1607 2G and MMP7-181 G allele
      were associated with high risk of BC, which was quite evident amongst smokers
      too. BCG treated NMIBC patients reflected protective effect for 2G allele carrier
      (1G/2G + 2G/2G) of MMP1-1607. This study provided new support for the association
      of MMP1-1607 and MMP7-181 in bladder cancer development, the tumorigenic effect
      of which was observed to be more enhanced in case of tobacco exposure.

PMID- 20826917
TI  - Diagnostic and prognostic utility of PD-1 in B cell lymphomas.
AB  - AIMS: Programmed death-1 (PD-1) is expressed by germinal center-associated helper
      T-cells and acts as a negative regulator of the immune system. PD-1 is
      encountered on tumor cells of angioimmunoblastic T-cell lymphoma and is a
      postulated diagnostic marker in chronic lymphocytic leukemia (CLL/SLL). Recent
      data suggest prognostic importance of PD-1 in follicular lymphoma (FL). We
      assessed the diagnostic potential and the prognostic importance of PD-1 in B-cell
      lymphomas. METHODS: Distribution of PD-1+ lymphocytes in B-cell lymphomas was
      studied on 403 cases. Correlation with known biologic and clinical key data was
      performed. Prognostic cut-off scores were determined by receiver operating curve
      analysis. RESULTS: PD-1+ tumor-infiltrating lymphocytes were numerous in
      extranodal marginal zone lymphomas and FL. Their amount decreased from FL grade 1
      to grade 3 and to FL with transformation to diffuse large B-cell lymphoma. An
      increased amount of PD-1 tumor-infiltrating lymphocytes above the prognostic cut
      off score (> 2.8%) was a positive prognostic factor of disease-specific survival
      (DSS) in FL-patients. Five percent of the studied 66 CLL/SLL cases showed
      unequivocal PD-1 positivity of neoplastic cells. CONCLUSIONS: Increased number of
      PD-1+ tumor-infiltrating lymphocytes is associated with significantly improved
      DSS in FL and may be useful to predict its heterogeneous clinical behavior. PD-1
      has probably limited diagnostic value for primary histopathological CLL/SLL
      diagnostics.

PMID- 20826918
TI  - Platelet markers correlate with glycemic indices in diabetic, but not diabetic
      myelodysplastic patients with normal platelet count.
AB  - BACKGROUND: Altered thrombocyte morphology and function have been reported in
      patients with diabetes mellitus (DM) type 2. The aim of the present study was to
      determine the associations between platelet morphology markers and hemoglobin A1C
      (HbA(1c)), fasting glucose (FG), hypertension and coronary heart disease (CHD) in
      patients with myelodysplastic syndromes (MDS) and DM, in patients with DM and in
      controls. METHODS: This cross-sectional study included 30 cases with primary MDS
      with normal platelet count and non-insulin dependent diabetes, 30 non-insulin
      dependent diabetic patients and 30 non-diabetic, non-MDS controls matched on age
      and gender. RESULTS: After adjusting for body mass index, platelet number, CHD
      and hypertension, HbA(1c) and FG were significant predictors of mean platelet
      volume (MPV) and platelet distribution width (PDW) in diabetic patients. There
      was no correlation between platelet parameters and HbA(1c) or FG in diabetic MDS
      patients. In controls, FG and hypertension predicted significant differences in
      platelet morphology. Platelet count correlated with platelet morphology in
      diabetic MDS and control groups, but not in diabetics. CONCLUSIONS: MPV and PDW
      are associated with glycemic indices in diabetic patients but not in diabetic MDS
      patients with normal platelet counts. Non-diabetic controls also exhibit FG
      related changes in platelet morphology. This suggests other factors inherent to
      bone marrow dysplasia, platelet turnover and biochemistry, or vascular
      environment affect platelet morphology in diabetic MDS patients even with normal
      platelet count. Platelet morphology in this population may be an early marker for
      myelodysplasia. These findings also support platelet morphology change as a
      marker for elevated macrovascular disease risk.

PMID- 20826931
TI  - Impacts of anti-EGFR monoclonal antibody in prostate cancer PC3 cells.
AB  - Epidermal growth factor receptor (EGFR) network appears to be a rich target for
      prostate cancer. Thus, in this current investigation, to pursue our newly
      developed anti-EGFR monoclonal antibody (mAb) in prostate cancer, its inhibitory
      effect was investigated in PC3 cells. The binding specificity of antibody was
      examined by flow cytometry and immunofluorescence staining. The cultivated cells
      were treated with various doses of the anti-EGFR mAb at different time points and
      the cellular and/or molecular impacts were assessed. MTT assay was utilized to
      examine the cytotoxic effects. Semi-quantitative RT-PCR was used to evaluate the
      expression of EGFR and some important apoptosis signaling molecules (e.g., MAPK
      1, STAT-5, Akt-1 kinase). Flow cytometric and immunofluorescence staining
      analyses showed that the anti-EGFR mAb can bind to EGFR with high specificity.
      The results revealed that the anti-EGFR mAb can inhibit cell growth in a dose and
      time dependent manner. RT-PCR analysis revealed that the binding of anti-EGFR mAb
      to its receptors can eventually result in downregulation of Akt-1 kinase gene,
      but not MAPK-1, STAT-5 and EGFR genes. Based on our findings, it can be concluded
      that Akt-1 is the most important downstream signaling molecules affected by anti
      EGFR mAbs.

PMID- 20826932
TI  - Selection of naturally occurring autoantibodies to interleukin-18 from phage
      display library.
AB  - Four unique phage single-chain variable fragments (scFvs) to recombinant human
      interleukin 18 (IL-18) has been selected from a naive combinatorial library of
      human scFvs. Binding of unique phage antibodies with IL-18 was tested by ELISA
      and Western-blotting. No cross reactivity with tumor necrosis factor alpha,
      interferons alpha and gamma was shown for the selected antibodies. The gene
      segments encoding V(D)J regions of selected antibodies exhibited a high degree of
      homology to germline genes, therefore we suggest that the selected scFv's belong
      to repertoire of naive autoantibodies.

PMID- 20826933
TI  - The influence of music on static posturography.
AB  - It is well known that high intensity sounds modify balance by activating the
      saccule, which is sensitive to both vestibular and acoustic stimuli. Few studies
      have examined the effects of music on the postural responses in healthy subjects.
      The aim of this study was to evaluate the influence of different types of music
      (Mozart, Kohler, Kohler with a carrier of 12 KHz and subjects' favourite music)
      on twelve healthy subjects standing on a stabilometric platform. With each type
      of music, all subjects underwent static posturography with eyes opened and eyes
      closed, and with and without foam pads. We evaluated the length and the surface
      of body sway and the correlation between them, and we analyzed the visual,
      vestibular and somatosensory sub-components. Listening to different types of
      music did not significantly change the stabilometric variables, with the
      exception of listening to Mozart's Jupiter, which caused a significant reduction
      in the visual component with a consequent increase in both the vestibular and
      somatosensory inputs. Further studies are needed to determine the effect of
      Mozart's music in modifying the sensory strategy in the rehabilitation of
      patients with vestibular impairments.

PMID- 20826934
TI  - Age effect on the Gaze Stabilization test.
AB  - Impairments of the vestibular-ocular reflex (VOR) lead to a decline in visual
      acuity during head movements. Dynamic visual acuity (DVA) testing is a sensitive
      assessment tool for detecting VOR impairments. DVA evaluates accuracy of visual
      acuity during fixed velocity head movements. In contrast, the Gaze Stabilization
      test (GST) is a new functional evaluation of the VOR that identifies a person's
      maximum head velocity (in degrees per second) a person can maintain with stable
      vision of a target (i.e. optotype). The objective of this study was to evaluate
      the effect of age on the GST in participants without vestibular disease. The
      study was conducted in a vestibular and balance laboratory at a tertiary medical
      center. A total of 87 healthy adult volunteers were included in this study. The
      main outcome measure was the association between age and both GST maximum head
      velocity in the yaw (right/left) plane and velocity symmetry. A significant
      negative correlation was found between age and maximum head velocity (r =-0.469,
      p< 0.001). Our results suggest that age should be considered when interpreting
      GST results in the yaw plane, however standardization of testing methods should
      be established as variation in results has been reported in the literature.

PMID- 20826935
TI  - The reliability, stability, and concurrent validity of a test of gaze
      stabilization.
AB  - The gaze stabilization test (GST) is a computerized test of the vestibulo-ocular
      reflex that reports maximum head velocity while maintaining fixed visual acuity.
      The GST thus assesses the vestibulo-ocular reflex differently from the dynamic
      visual acuity test (DVAT). The purpose of this study was to assess the
      reliability, stability, and validity of the GST in a healthy young and older
      population. Forty subjects (20 older adults with mean (SD) age of 76.3 (5.3) and
      20 young controls with mean (SD) age of 25.2 (3.2)) performed the GST and DVAT
      assessments. The version of the GST used in this study has a tunneled mirror
      system to ensure a consistent participant distance of 4 m from the computer
      screen. All subjects repeated trials within 30 minutes of initial testing. Twenty
      subjects (10 from each age group) returned 7-10 days later to repeat the GST and
      DVAT assessments. Vestibular symptoms were assessed before and after GST and DVAT
      assessments. The mean (SD) GST scores for the older group were 123 (33) deg/s in
      the yaw plane and 108 (27) deg/s in the pitch plane. For the young group, mean
      (SD) GST scores were 157 (34) deg/s in the yaw plane and 141(25) deg/s in the
      pitch plane. There was a significant between-group difference for GST scores in
      both yaw and pitch planes (p< 0.01). The intraclass correlation coefficient (ICC)
      for GST scores performed on the same day was 0.75 in the yaw plane and 0.69 in
      the pitch plane. The ICC including the 20 subjects who repeated the GST within 7
      10 days was 0.59 in the yaw plane and 0.54 in the pitch plane. In general, GST
      was more stable than DVAT. GST was more stable in younger vs. older subjects
      whereas DVAT was more stable in older vs. younger subjects. Concurrent validity,
      determined by Spearman correlation coefficients between GST and DVAT loss results
      were -0.62 in the yaw plane and -0.38 in the pitch plane (p< 0.02). These results
      suggest that the gaze stabilization test (GST) has good same-day test-retest
      reliability and stability in healthy young and older adults. The moderate
      correlation between same-day GST and DVAT loss scores suggest the two tests may
      be measuring similar, but different constructs.

PMID- 20826936
TI  - Auditory-pupillary responses in deaf subjects.
AB  - Pupillary dilation in response to sound stimuli is well established and is
      generally considered to represent a startle reflex to sound. We believe that the
      auditory-pupillary response represents not only a simple startle reflex to sound
      stimuli but also represents a reaction to stimulation of other sense organs, such
      as otolith organs. Eight young healthy volunteers without a history of hearing
      and equilibrium problems and 12 subjects with bilateral deafness participated in
      this study. Computer pupillography was used to analyze the auditory-pupillary
      responses of both eyes in all subjects. We found that auditory-pupillary
      responses occurred even in subjects with bilateral deafness and that this
      response was comparable to those of normal subjects. We propose that the auditory
      pupillary response also relates to vestibular function. Thus, assessing the
      auditory-pupillary response may be useful for evaluating the vestibulo-autonomic
      response in patients with peripheral disequilibrium.

PMID- 20826937
TI  - Head tilt response: A complementary test to the Subjective Visual Vertical.
AB  - This paper studies the phenomenon of the perceived vertical by means of a novel
      dynamic experiment. This task is inspired in the Subjective Visual Vertical test
      and can be regarded as complementary in terms of how the information involved
      varies (visual, otolithic and neck proprioception). The experiment consists in
      presenting a white stripe in a pair of virtual reality goggles and adjusting the
      roll angle of the head until the stripe is aligned with the gravitational
      vertical. The roll angle of the head is measured and recorded along each trial
      where the white stripe changes position four times, after a specific amount of
      time. The task was run on a group of 28 normal subjects and a small sample of 5
      patients with vestibular hypofunction. Six parameters derived from Control Theory
      were extracted from the data to characterize the subject transient response. All
      parameters for normal subjects were found to be normally distributed.
      Experimental results show that discrimination is possible between normal subjects
      and patients using just one or two of the parameters studied.

PMID- 20826938
TI  - Dizziness: A common, troublesome symptom but often treatable.
AB  - OBJECTIVE: To investigate the prevalence of self-rated dizziness/unsteadiness and
      health as well as to estimate the proportion of participants with peripheral
      vestibular disorders. METHODS: Altogether, 2547 participants (66%) participated
      in an epidemiological cross-sectional study, including self-rated questions about
      dizziness/unsteadiness, concomitant auditory symptoms and self-rated general,
      psychosocial and mental health. RESULTS: The overall prevalence of dizziness was
      21% and higher among women (27%) than men (14%) (p< 0.001). Dizziness, provoked
      by the movement of lying-down (benign paroxysmal positional vertigo), was noted
      in 5% of the participants with the symptom occurring more often in women than in
      men (p< 0.001). Twenty-four percent of the men and 21% of the women with
      dizziness simultaneously experienced a sense of rotation and loss of hearing and
      tinnitus. Fifteen percent reported falls because of dizziness. Both men and women
      suffering from dizziness symptoms perceived worse self-rated health generally,
      psychosocially and mentally than those without symptoms of dizziness (p< 0.001).
      CONCLUSION: Dizziness-related symptoms are common in all age groups and may
      manifest worse self-rated health. About 50% of the participants had symptoms
      indicating origin of peripheral vestibular disorders. Self-rated questions seem
      capable of identifying patients for referral to clinical examinations and
      subsequently those who can be successfully treated.

PMID- 20826940
TI  - Neurosecretion in reproductive behaviour of leeches.

PMID- 20826941
TI  - Fatal attraction: bacteria exploit fungal heterokaryon incompatibility to obtain
      nutrients.

PMID- 20826942
TI  - Human papillomavirus and tar hypothesis for squamous cell cervical cancer.

PMID- 20826943
TI  - Alfred Russel Wallace deserves better.
AB  - During 2009, while we were celebrating Charles Darwin and his The origin of
      species, sadly, little was said about the critical contribution of Alfred Russel
      Wallace (1823-1913) to the development of the theory of evolution. Like Darwin,
      he was a truly remarkable nineteenth century intellect and polymath and,
      according to a recent book by Roy Davies (The Darwin conspiracy: origins of a
      scientific crime), he has a stronger claim to the Theory of Evolution by Natural
      Selection than has Darwin. Here we present a critical comparison between the
      contributions of the two scientists. Sometimes referred to as 'The other beetle
      hunter' and largely neglected for many decades, Wallace had a far greater
      experience of collecting and investigating animals and plants from their native
      habitats than had Darwin. He was furthermore much more than a pioneer
      biogeographer and evolutionary theorist, and also made contributions to
      anthropology, ethnography, geology, land reform and social issues. However, being
      a more modest, self-deprecating man than Darwin, and lacking the latter's
      establishment connections, Wallace's contribution to the theory of evolution was
      not given the recognition it deserved and he was undoubtedly shabbily treated at
      the time. It is time that Wallace's relationship with Darwin is reconsidered in
      preparation for 2013, the centenary of Wallace's death, and he should be
      recognized as at least an equal in the Wallace-Darwin theory of evolution.

PMID- 20826944
TI  - INDeGenIUS, a new method for high-throughput identification of specialized
      functional islands in completely sequenced organisms.
AB  - Genomic islands (GIs) are regions in the genome which are believed to have been
      acquired via horizontal gene transfer events and are thus likely to be
      compositionally distinct from the rest of the genome. Majority of the genes
      located in a GI encode a particular function. Depending on the genes they encode,
      GIs can be classified into various categories, such as 'metabolic islands',
      'symbiotic islands', 'resistance islands', 'pathogenicity islands', etc. The
      computational process for GI detection is known and many algorithms for the same
      are available. We present a new method termed as Improved N-mer based Detection
      of Genomic Islands Using Sequence-clustering (INDeGenIUS) for the identification
      of GIs. This method was applied to 400 completely sequenced species belonging to
      proteobacteria. Based on the genes encoded in the identified GIs, the GIs were
      grouped into 6 categories: metabolic islands, symbiotic islands, resistance
      islands, secretion islands, pathogenicity islands and motility islands. Several
      new islands of interest which had previously been missed out by earlier
      algorithms were picked up as GIs by INDeGenIUS. The present algorithm has
      potential application in the identification of functionally relevant GIs in the
      large number of genomes that are being sequenced. Investigation of the predicted
      GIs in pathogens may lead to identification of potential drug/vaccine candidates.

PMID- 20826945
TI  - Transcription pattern of UL131A-128 mRNA in clinical strains of human
      cytomegalovirus.
AB  - Human cytomegalovirus (HCMV) mRNA was obtained from human embryonic lung
      fibroblast cells infected by HCMV clinical strains from urine samples of infants
      at different kinetic periods. The cDNA of UL131A-128 mRNAs was amplified using
      reverse transcription-polymerase chain reaction (RT-PCR) and analysed by
      sequencing. Meanwhile, clones containing UL131A-128 transcripts in an HCMV cDNA
      library of a clinical strain were selected and sequenced. It was demonstrated
      that UL131A-128 mRNA was expressed with immediately early, early and late
      kinetics. Sequences obtained by RT-PCR showed that the UL131A gene consisted of
      two exons and the coding region of the UL130 gene was not interrupted by any
      intron in the region as reported earlier. However, the transcript of the UL128
      gene showed two patterns: one pattern consisted of three exons as reported
      earlier; the other contained the three exons and also the first intron. Moreover,
      the above characteristics of UL131A-128 spliced transcripts were confirmed by the
      sequences of clones selected from the HCMV cDNA library. Our results demonstrated
      that the UL131A, UL130 and UL128 genes were transcribed with the 3'-coterminal,
      although the initiation points of their mRNA may be different. The variation in
      the transcripts found in our study indicated the complex nature of transcription
      of UL131A-128 genes in clinical strains of HCMV.

PMID- 20826946
TI  - The ruthenium complex cis-(dichloro)tetrammineruthenium(III) chloride induces
      apoptosis and damages DNA in murine sarcoma 180 cells.
AB  - Ruthenium (III) complexes are increasingly attracting the interest of researchers
      due to their promising pharmacological properties. Recently, we reported that the
      cis-(dichloro)tetrammineruthenium (III) chloride compound has cytotoxic effects
      on murine sarcoma 180 (S-180) cells. In an effort to understand the mechanism
      responsible for their cytotoxicity, study we investigated the genotoxicity, cell
      cycle distribution and induction of apoptosis caused by cis- (dichloro)
      tetrammineruthenium (III) chloride in S-180 tumour cells. cis-(dichloro)
      tetrammineruthenium (III) chloride treatment induced significant DNA damage in S
      180 cells, as detected by the alkaline comet assay. In the cell cycle analysis,
      cis-(dichloro) tetrammineruthenium (III) chloride caused an increase in the
      number of cells in G1 phase, accompanied by a decrease in the S and G2 phases
      after 24 h of treatment. In contrast, the cell cycle distribution of S-180 cells
      treated with cis-(dichloro) tetrammineruthenium (III) chloride for 48 h showed a
      concentration-dependent increase in the sub-G1 phase (indicating apoptosis), with
      a corresponding decrease in cells in the G1, S and G2 phases. In addition, cis
      (dichloro) tetrammineruthenium(III) chloride treatment induced apoptosis in a
      time-dependent manner,as observed by the increased numbers of annexin V-positive
      cells. Taken together, these findings strongly demonstrate that DNA damage, cell
      cycle changes and apoptosis may correlate with the cytotoxic effects of cis
      (dichloro) tetrammineruthenium (III) chloride on S-180 cells.

PMID- 20826947
TI  - Isolation and characterization of a gene encoding a polyethylene glycol-induced
      cysteine protease in common wheat.
AB  - Plant cysteine protease (CP) genes are induced by abiotic stresses such as
      drought, yet their functions remain largely unknown. We isolated the full-length
      cDNA encoding a Triticum aestivum CP gene, designated TaCP, from wheat by the
      rapid amplification of cDNA ends (RACE) method. Sequence analysis revealed that
      TaCP contains an open reading frame encoding a protein of 362 amino acids, which
      is 96% identical to barley cysteine protease HvSF42. The TaCP transcript level in
      wheat seedlings was upregulated during polyethylene glycol (PEG) stress, with a
      peak appearing around 12 h after treatment. TaCP expression level increased
      rapidly with NaCl treatment at 48 h. TaCP responded strongly to low temperature
      (4 degree C) treatment from 1 h post-treatment and reached a peak of about 40
      fold at 72 h. However, it showed only a very slight response to abscisic acid
      (ABA). More than one copy of TaCP was present in each of the three genomes of
      hexaploid wheat and its diploid donors. TaCP fused with green fluorescent protein
      (GFP) was located in the plasma membrane of onion epidermis cells. Transgenic
      Arabidopsis plants overexpressing TaCP showed stronger drought tolerance and
      higher CP activity under water-stressed conditions than wild-type Arabidopsis
      plants. The results suggest that TaCP plays a role in tolerance to water deficit.

PMID- 20826948
TI  - Designing exons for human olfactory receptor gene subfamilies using a
      mathematical paradigm.
AB  - Ligands for only two human olfactory receptors are known. One of them, OR1D2,
      binds to Bourgeonal, a volatile chemical constituent of the fragrance of the
      mythical flower, Lily of the valley or Our Lady's tears, Convallaria majalis
      (also the national flower of Finland). OR1D2, OR1D4 and OR1D5 are three full
      length olfactory receptors present in an olfactory locus in the human genome.
      These receptors are more than 80% identical in DNA sequences and have 108 base
      pair mismatches among them. Apparently, these mismatch positions show no striking
      pattern using computer pattern recognition tools. In an attempt to find a
      mathematical rule in those mismatches, we find that an L-system generated
      sequence can be inserted into the OR1D2 subfamily-specific star model and novel
      full-length olfactory receptors can be generated. This remarkable mathematical
      principle could be utilized for making new subfamily olfactory receptor members
      from any olfactory receptor subfamily. The aroma and electronic nose industry
      might utilize this rule in future.

PMID- 20826949
TI  - A new multi-wavelength model-based method for determination of enzyme kinetic
      parameters.
AB  - Lineweaver-Burk plot analysis is the most widely used method to determine enzyme
      kinetic parameters. In the spectrophotometric determination of enzyme activity
      using the Lineweaver-Burk plot, it is necessary to find a wavelength at which
      only the substrate or the product has absorbance without any spectroscopic
      interference of the other reaction components. Moreover, in this method,
      different initial concentrations of the substrate should be used to obtain the
      initial velocities required for Lineweaver-Burk plot analysis. In the present
      work, a multi-wavelength model-based method has been developed and validated to
      determine Michaelis-Menten constants for some enzyme reactions. In this method, a
      selective wavelength region and several experiments with different initial
      concentrations of the substrate are not required. The absorbance data of the
      kinetic assays are fitted by non-linear regression coupled to the numeric
      integration of the related differential equation. To indicate the applicability
      of the proposed method, the Michaelis-Menten constants for the oxidation of
      phenanthridine, 6-deoxypenciclovir and xanthine by molybdenum hydroxylases were
      determined using only a single initial concentration of the substrate, regardless
      of any spectral overlap.

PMID- 20826950
TI  - Identification, tissue distribution and evaluation of brain neuropeptide Y gene
      expression in the Brazilian flounder Paralichthys orbignyanus.
AB  - Neuropeptide Y (NPY) is one of the most potent stimulants of food intake in
      vertebrates, mammals and fish. However, the present knowledge about feeding
      behaviour in fish is still limited and based on studies in a few species. The
      Brazilian flounder Paralichthys orbignyanus is being considered for aquaculture,
      and it is important to understand the mechanisms regulating feeding in order to
      improve its performance in captivity. The objectives of this study were to clone
      NPY cDNA, evaluate the mRNA levels in different tissues of flounder, and also
      evaluate brain NPY expression to associate food intake with NPY expression
      levels. A 597 bp NPY cDNA was cloned from Brazilian flounder brain. NPY
      expression was detected in all the peripheral tissues analysed. No significant
      differences were observed in brain NPY gene expression over 24 h after food
      intake at a temperature of 15 +or- 3 degrees C. No correlation was observed among
      plasma glucose, total protein, cholesterol, triglycerides and NPY expression
      levels during this 24 h period. On the other hand, mRNA levels were increased
      after two weeks of fasting at elevated temperatures. Our results suggest that NPY
      mRNA levels in Brazilian flounder are affected by temperature.

PMID- 20826951
TI  - Mitosis and cell death in the optic lobes of workers, queens and drones of the
      honey bee (Apis mellifera) during metamorphosis.
AB  - Colonies of the honey bee, Apis mellifera, consist of males and two female
      castes: workers and queens. The castes and males from A. mellifera have a
      distinct morphology, physiology and behaviour that correlate with their roles in
      the society and are characterized by some brain polymorphisms. Compound eyes are
      one of the characteristics that differ among the castes and sexes. A. mellifera
      is a holometabolous insect; therefore, the development of adult organs during
      metamorphosis, which will produce these differences, requires the precise
      coordination of three main programmed cellular processes: proliferation,
      differentiation and death. These processes take place simultaneously during
      pupation. Our purpose was to investigate cell division and death in the optic
      lobes (OL) of workers, queens and males during pupation to identify how the
      differences in the compound eyes in adults of these classes are achieved. The
      results showed that OL differentiation follows a similar pattern in the three
      classes of individuals studied, without structural differences in their
      development. The main non-structural differences involve cell division, mortality
      rates and timing. The results suggest a modelling of the brain during
      differentiation, which contributes to the specific functions of each individual
      class.

PMID- 20826952
TI  - Unusual radioresistance of nitrogen-fixing cultures of Anabaena strains.
AB  - Nitrogen-fixing cultures of two species of the filamentous, heterocystous
      cyanobacterium Anabaena, namely Anabaena sp. strain L-31 and Anabaena torulosa
      were found to be highly tolerant to 60Co gamma radiation. No adverse effect on
      diazotrophic growth and metabolism were observed up to a dose of 5 kGy. At higher
      doses, radiation tolerance showed a correspondence with the inherent
      osmotolerance, with Anabaena L-31 being the more radiation tolerant as well as
      osmotolerant strain. In Anabaena L-31, exposure to 6 kGy of gamma rays resulted
      in genome disintegration, but did not reduce viability. Irradiation delayed
      heterocyst differentiation and nitrogen fixation, and marginally affected
      diazotrophic growth. All the affected parameters recovered after a short lag,
      without any discernible postirradiation phenotype. The radiation tolerance of
      these Gram-negative photoautodiazotrophs is comparable with that of the
      adiazotrophic photoautotrophic cyanobacterium Chroococcidiopsis or adiazotrophic
      heterotroph Deinococcus radiodurans. This is the first report of extreme
      radioresistance in nitrogen-fixing Anabaena cultures.

PMID- 20826953
TI  - Thirty-seven transcription factor genes differentially respond to a harpin
      protein and affect resistance to the green peach aphid in Arabidopsis.
AB  - The harpin protein HrpN Ea induces Arabidopsis resistance to the green peach
      aphid by activating the ethylene signalling pathway and by recruiting EIN2, an
      essential regulator of ethylene signalling, for a defence response in the plant.
      We investigated 37 ethylene-inducible Arabidopsis transcription factor genes for
      their effects on the activation of ethylene signalling and insect defence. Twenty
      eight of the 37 genes responded to both ethylene and HrpN Ea, and showed either
      increased or inhibited transcription, while 18 genes showed increased
      transcription not only by ethylene but also by HrpN Ea. In response to HrpN Ea,
      transcription levels of 22 genes increased, with AtMYB44 being the most
      inducible, six genes had decreased transcript levels, and nine remained
      unchanged. When Arabidopsis mutants previously generated by mutagenicity at the
      37 genes were surveyed, 24 mutants were similar to the wild type plant while four
      mutants were more resistant and nine mutants were more susceptible than wild type
      to aphid infestation. Aphid-susceptible mutants showed a greater susceptibility
      for atmyb15, atmyb38 and atmyb44, which were generated previously by T-DNA
      insertion into the exon region of AtMYB15 and the promoter regions of AtMYB38 and
      AtMYB44. The atmyb44 mutant was the most susceptible to aphid infestation and
      most compromised in induced resistance. Resistance accompanied the expression of
      PDF1.2, an ethylene signalling marker gene that requires EIN2 for transcription
      in wild type but not in atmyb15, atmyb38, and atmyb44, suggesting a disruption of
      ethylene signalling in the mutants. However, only atmyb44 incurred an abrogation
      in induced EIN2 expression, suggesting a close relationship between AtMYB44 and
      EIN2.

PMID- 20826954
TI  - Interactions between ethylene, abscisic acid and cytokinin during germination and
      seedling establishment in Arabidopsis.
AB  - In order to investigate the interaction of the plant hormones ethylene, abscisic
      acid (ABA) and cytokinin in seed germination and early seedling development, we
      studied germination in ethylene-related mutants of Arabidopsis. Mutations in the
      genes etr1 and ein2, which reduce ethylene responses, showed increased dormancy
      and a delay in germination in comparison with wild type. Mutations in etr1, ein2
      and ein6 also resulted in increased sensitivity to ABA with respect to inhibition
      of germination. Conversely, mutations in ctr1 and eto3, which lead to an
      increased ethylene response and overproduction of ethylene, respectively,
      decreased sensitivity to ABA during germination. Increased ABA sensitivity was
      also effected in wild type seeds by the presence during germination of AgNO 3, an
      inhibitor of ethylene action. The addition of the cytokinin N-6 benzyl adenine
      (BA) reversed the increased sensitivity of ethylene-resistant mutants to ABA. The
      action of cytokinin in reversing increased ABA sensitivity of ethylene-resistant
      mutants also suggests that at least part of the action of cytokinin in promoting
      germination is independent of its role in stimulating ethylene production. These
      observations further extend the evidence in support of interaction between
      ethylene, ABA and cytokinin signalling in controlling seed germination and early
      seedling development in Arabidopsis.

PMID- 20826955
TI  - Overexpression of OsWRKY72 gene interferes in the abscisic acid signal and auxin
      transport pathway of Arabidopsis.
AB  - Through activating specific transcriptional programmes, plants can launch
      resistance mechanisms to stressful environments and acquire a new equilibrium
      between development and defence. To screen the rice WRKY transcription factor
      which functions in abiotic stress tolerance and modulates the abscisic acid (ABA)
      response, we generated a whole array of 35S-OsWRKY transgenic Arabidopsis. In
      this study, we report that 35S-OsWRKY72 transgenic Arabidopsis, whose seed
      germination was retarded under normal conditions, emerged more sensitive to
      mannitol, NaCl, ABA stresses and sugar starvation than vector plants. Meanwhile,
      35S-OsWRKY72 transgenic Arabidopsis displayed early flowering, reduced apical
      dominance, lost high temperature-induced hypocotyl elongation response, and
      enhanced gravitropism response, which were similar to the auxin-related gene
      mutants aux1, axr1 and bud1. Further, semi-quantitative RT-PCR showed that the
      expression patterns of three auxin-related genes AUX1, AXR1 and BUD1 were
      significantly altered in rosette leaves and infl orescences of 35S-OsWRKY72
      plants compared with control Arabidopsis, and two ABA-related genes ABA2 and ABI4
      were induced in 35S-OsWRKY72 seedlings. In addition, northern blot analysis
      indicated that, in rice, OsWRKY72 was inducible by polyethylene glycol (PEG),
      NaCl, naphthalene acetic acid (NAA), ABA and 42 degrees C, similar to its
      orthologue AtWRKY75 in Arabidopsis, implying that these two WRKY genes might be
      required for multiple physiological processes in their plants. Together, these
      results suggest that OsWRKY72 interferes in the signal cross-talk between the ABA
      signal and auxin transport pathway in transgenic Arabidopsis.

PMID- 20826956
TI  - Hormonal regulation of gluconeogenic gene transcription in the liver.
AB  - Glucose homeostasis in mammals is achieved by the actions of counterregulatory
      hormones, namely insulin, glucagon and glucocorticoids. Glucose levels in the
      circulation are regulated by the liver, the metabolic centre which produces
      glucose when it is scarce in the blood. This process is catalysed by two rate
      limiting enzymes, phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6
      phosphatase (G6Pase) whose gene expression is regulated by hormones. Hormone
      response units (HRUs) present in the two genes integrate signals from various
      signalling pathways triggered by hormones. How such domains are arranged in the
      regulatory region of these two genes, how this complex regulation is accomplished
      and the latest advancements in the field are discussed in this review.

PMID- 20826958
TI  - Neuromuscular blockade and outcome in cardiac anesthesia.

PMID- 20826959
TI  - Establishing a new cardiac surgical unit: challenges and solutions.

PMID- 20826957
TI  - Complex regulation of sister kinetochore orientation in meiosis-I.
AB  - Kinetochores mediate chromosome movement during cell division by interacting with
      the spindle microtubules. Sexual reproduction necessitates the daunting task of
      reducing ploidy (number of chromosome sets) in the gametes, which depends upon
      the specialized properties of meiosis. Kinetochores have a central role in the
      reduction process. In this review, we discuss the complexity of this role of
      kinetochores in meiosis-I.

PMID- 20826960
TI  - Atrial fibrillation after cardiac surgery.
AB  - Once considered as nothing more than a nuisance after cardiac surgery, the
      importance of postoperative atrial fibrillation (POAF) has been realized in the
      last decade, primarily because of the morbidity associated with the condition.
      Numerous causative factors have been described without any single factor being
      singled out as the cause of this complication. POAF has been associated with
      stroke, renal failure and congestive heart failure, although it is difficult to
      state whether POAF is directly responsible for these complications. Guidelines
      have been formulated for prevention of POAF. However, very few cardiothoracic
      centers follow any form of protocol to prevent POAF. Routine use of prophylaxis
      would subject all patients to the side effects of anti-arrhythmic drugs, while
      only a minority of the patients do actually develop this problem postoperatively.
      Withdrawal of beta blockers in the postoperative period has been implicated as
      one of the major causes of POAF. Amiodarone, calcium channel blockers and a
      variety of other pharmacological agents have been used for the prevention of
      POAF. Atrial pacing is a non-pharmacological measure which has gained popularity
      in the prevention of POAF. There is considerable controversy regarding whether
      rate control is superior to rhythm control in the treatment of established atrial
      fibrillation (AF). Amiodarone plays a central role in both rate control and
      rhythm control in postoperative AF. Newer drugs like dronedarone and ranazoline
      are likely to come into the market in the coming years.

PMID- 20826961
TI  - Sugammadex--a short review and clinical recommendations for the cardiac
      anesthesiologist.
AB  - This review outlines the basic pharmacodynamic and pharmacokinetic properties of
      sugammadex for the cardiac anesthesiologist. It describes the different clinical
      scenarios when sugammadex can be used during cardiac surgery and gives clinical
      recommendations. Sugammadex is a unique reversal drug that binds a chemical
      complex with rocuronium and vecuronium, by which the neuromuscular blockade is
      quickly reversed. It is free of any clinical side-effects and doses of 2 mg/kg or
      more reliably reverse neuromuscular blockade within 5-15 min, depending on the
      depth of the neuromuscular blockade. Doses below 2 mg/kg should be avoided at any
      time because of the inherent risk of recurarization. Sugammadex should not
      replace good clinical practice--titration of neuromuscular blocking drugs to
      clinical needs and objective monitoring of neuromuscular blockade in the
      operating room or intensive care unit. Neuromuscular transmission should be
      determined in all patients before sugammadex is considered and 5 min after its
      administration to ensure that extubation is performed with normal neuromuscular
      transmission.

PMID- 20826962
TI  - A randomized trial of anesthetic induction agents in patients with coronary
      artery disease and left ventricular dysfunction.
AB  - The deleterious effects of anesthetic agents in patients suffering from coronary
      artery disease are well known. The risk increases when a patient has compromised
      ventricular function. There is a paucity of literature regarding the choice of
      the suitable agent to avoid deleterious effects in such patients. The use of
      etomidate and propofol has been considered superior to other intravenous
      anesthetic agents in these groups of patients. The aim of the present study is to
      compare the hemodynamic effects of anesthesia induction with etomidate,
      thiopentone, propofol, and midazolam in patients with coronary artery disease and
      left ventricular dysfunction. This randomized clinical trail was conducted at the
      All Indian Institute of Medical Sciences, New Delhi, India. Sixty patients with
      coronary artery disease and left ventricular dysfunction (ejection fraction <
      45%) scheduled for elective coronary artery bypass surgery participated in this
      study. After stabilization baseline hemodynamic data stroke volume variation and
      systemic vascular resistance index were recorded for all patients (Flo Trac TM
      sensor with Vigileo cardiac output monitor used for hemodynamic monitoring). The
      patients were randomly alloted to one of the four groups and the intravenous
      induction agent was administered for over 60-90 seconds (Group E--Etomidate 0.2
      mg/Kg; Group M--Midazolam 0.15 mg/Kg; Group T--Thiopentone 5 mg/Kg; Group P-
      Propofol 1.5 mg/Kg). Hemodynamic data were recorded at one minute intervals
      starting from induction till seven minutes after intubation,--the end point of
      the present study. There was a significant decrease in the heart rate in
      comparison to the baseline(-7 to -15%, P = 0.001), mean arterial pressure (-27 to
      -32%, P = 0.001), cardiac index (-36 to -38%, P = 0.001), and stroke volume index
      (-27 to -34%, P = 0.001) after induction in all four groups. The hemodynamic
      response was similar in all the four groups. There was no significant change in
      central venous pressure and stroke volume variation (SVV) during induction and
      intubation, while the effects on the systemic vascular resistance index (SVRI)
      were variable. The midazolam group was the most effective in preventing
      intubation stress (tachycardia,hypertension). The change from baseline values in
      heart rate (+ 4%, P = 0.12) and mean arterial pressure (-1%, P = 0.77) after
      intubation were not statistically significant in the midazolam group. The
      etomidate group was the least effective of all the four groups in minimizing
      stress response, with statistically significant increase from baseline in both
      heart rate (P = 0.001) and mean arterial pressure (P = 0.001) at 1 minute after
      intubation. All the four anesthetic agents were acceptable for induction in
      patients with coronary artery disease and left ventricular dysfunction despite a
      30-40% decrease in the cardiac index. Clinician experience along with knowledge
      of the potential interactions (e.g., premedication, concurrent opioid use) is
      needed to determine hemodynamic stability during anesthetic induction in these
      patients with ventricular dysfunction.

PMID- 20826963
TI  - Thoracic epidural analgesia for off-pump coronary artery bypass surgery in
      patients with chronic obstructive pulmonary disease.
AB  - The benefits of thoracic epidural analgesia in patients undergoing coronary
      artery bypass grafting are well documented. However, the literature available on
      the role of high thoracic epidural analgesia (HTEA) in patients with chronic
      obstructive pulmonary disease undergoing off-pump coronary artery bypass graft
      (OPCAB) surgery is scarce. We conducted a randomized clinical trial to establish
      whether HTEA is beneficial in patients with chronic obstructive pulmonary disease
      undergoing elective OPCAB surgery. After institutional ethics board approval and
      informed consent, 62 chronic obstructive pulmonary disease patients undergoing
      elective OPCAB were randomly grouped into two (n = 31 each). Both groups received
      general anesthesia (GA), but in the HTEA group patients, TEA was also
      administered. Standardized surgical and anesthetic techniques were used for both
      the groups. Pulmonary function tests were performed pre-operatively, 6 h and 24 h
      post-extubation and on days 2, 3, 4 and 5 along with arterial blood gas analysis
      (ABG) analysis. Time for extubation (h) and time for oxygen withdrawal (h) were
      recorded. Pain score was assessed by the 10-cm visual analogue scale. All
      hemodynamic/oxygenation parameters were noted. Any complications related to the
      TEA were also recorded. Patients in the HTEA group were extubated earlier (10.8 h
      vs. 13.5 h, P < 0.01) and their oxygen withdrawal time was also significantly
      lower (26.26 h vs. 29.87 h, P < 0.01). The VAS score, both at rest and on
      coughing, was significantly lower in the HTEA group at all times, post
      operatively (P < 0.01). The forced vital capacity improved significantly at 6 h
      post-operatively in the HTEA group (P = 0.026) and remained significantly higher
      thereafter. A similar trend was observed in forced expiratory volume in the first
      second on day 2 in the HTEA group (P = 0.024). We did not observe any significant
      side-effects/mortality in either group. In chronic obstructive pulmonary disease
      patients undergoing elective OPCAB surgery, HTEA is a good adjunct to GA for
      early extubation, faster recovery of pulmonary function and better analgesia.

PMID- 20826964
TI  - Intraoperative anastomotic site detection and assessment of LIMA-to-LAD
      anastomosis by epicardial ultrasound in off-pump coronary artery bypass grafting-
      a prospective single-blinded study.
AB  - The study was done to detect the optimal site of left anterior descending (LAD)
      artery for grafting and for the assessment of geometrical and anatomical
      characteristics of left internal mammary artery (LIMA)-to-LAD artery anastomosis
      in elective off-pump coronary artery bypass grafting surgery. Fifteen consecutive
      patients who underwent coronary artery bypass graft (CABG) were included in the
      study. All the operations were performed by a single surgeon. Epicardial
      ultrasound probe was placed at the site of grafting for scanning and the site of
      anastomosis selected. The anticipated target site selected by the surgeon was
      scanned for patency, size, septal perforator branches, and presence of plaque and
      calcification. The surgeon identified the LAD artery in 12 patients. In three
      patients, the LAD artery was not visible. However, with epicardial ultrasound,
      the LAD artery was identified in all patients. In 6 of 15 patients, the
      anticipated target anastomotic site was changed to a clear segment either due to
      the presence of perforators or plaques or calcifications. In all 15 patients, the
      surgeon scored the anastomosis as good, based on his or her experience
      independent of the ultrasound image. The anastomotic score by the cardiac
      anesthesiologist showed 5 anastomoses with satisfactory results and 10
      anastomoses with good results. The study demonstrates that epicardial ultrasound
      scanning with a 10-MHz transducer provides reliable information in choosing the
      proper anastomotic site and allows proper visualization of LIMA-to-LAD
      anastomosis. All these measurements are easily obtained without risk of any
      complications and the method is not time consuming.

PMID- 20826965
TI  - Controlled transient respiratory arrest along with rapid right ventricular pacing
      for improving balloon stability during balloon valvuloplasty in pediatric
      patients with congenital aortic stenosis--a retrospective case series analysis.
AB  - Rapid right ventricular pacing is safe, effective, and established method to
      provide balloon stability during balloon aortic valvuloplasty (BAV). Controlled
      transient respiratory arrest at this point of time may further reduce left
      ventricular stroke volume, providing an additional benefit to maintain balloon
      stability. Two groups were studied. Among the 10 patients, five had rapid pacing
      alone (Group A), while the other five were provided with cessation of positive
      pressure breathing as well (Group B). The outcomes of BAV in the two groups of
      patients were studied. One patient in Group A had failed balloon dilatation even
      after the fourth attempt, while in Group B there were no failures. The peak
      systolic gradient reduction was higher in Group B (70.05% in comparison to 52.16%
      of group A). In Group A, five subjects developed aortic regurgitation (grade 2 in
      four and grade 3 in one, while no grade 3 aortic regurgitation developed in any
      patient in Group B). Controlled transient respiratory arrest along with rapid
      ventricular pacing may be effective in maintaining balloon stability and improve
      the outcome of BAV.

PMID- 20826966
TI  - Is EuroSCORE applicable to Indian patients undergoing cardiac surgery?
AB  - Indian patients undergoing cardiac surgery have different demographics, clinical
      profile as well as risk profile, compared to the western population. The purpose
      of this study was to validate the European System for Cardiac Operative Risk
      Evaluation (EuroSCORE) risk stratification model in Indian patients undergoing
      cardiac surgery in a single cardiac center. Data from 1000 consecutive adult
      patients undergoing cardiac surgery (coronary artery bypass grafting or valve
      surgery) were prospectively collected as per the EuroSCORE model. The model's
      validity was assessed on the basis of its calibration power (Hosmer-Lemeshow
      test) and discriminatory power [area under receiver operating characteristic
      curve]. The patients were divided into three risk groups on the basis of their
      EuroSCORE. The Hosmer-Lemeshow test revealed a good calibration power (P = 0.73)
      and the area under the ROC curve was 0.8278, suggesting a good discriminative
      power. The predicted mortality was similar to observed mortality in low- and
      moderate-risk patients but the observed mortality in high-risk patients (15.6%)
      was double that of predicted mortality (7.5%). The risk factors prevalent in
      European population were not observed in Indian population. EuroSCORE accurately
      predicts mortality in low and moderate-risk Indian patients undergoing cardiac
      surgery but is less predictive for high-risk Indian patients. Updating and
      improvisation of EuroSCORE by incorporation of risk factors associated with
      rheumatic valvular heart disease which is more prevalent in India, may enable it
      to accurately predict mortality in high-risk patients also.

PMID- 20826967
TI  - Anesthetic management of a patient with hypertrophic obstructive cardiomyopathy
      with dual-chamber pacemaker undergoing transurethral resection of the prostate.
AB  - We describe the anesthetic management of a patient with hypertrophic obstructive
      cardiomyopathy with dual-chamber pacemaker undergoing transurethral resection of
      the prostate. Anesthetic challenges included prevention and management of
      perioperative arrhythmias, maintenance of adequate preload, afterload and heart
      rate to relieve left ventricular outflow tract obstruction and considerations
      related to the presence of dual-chamber pacemaker and TURP. We recommend
      preoperative reprogramming of the DDD pacemaker, avoidance of magnet application
      during the procedure, application of electrosurgical unit current returning pad
      to the anterior aspect of the thigh, especially if monopolar cautery is used, use
      of central venous pressure line for estimation of preload and careful titration
      of anesthetic drugs to maintain stable hemodynamics.

PMID- 20826968
TI  - Cardiac herniation following completion pneumonectomy for bronchiectasis.
AB  - Sporadic reports on cardiac herniation are available in the literature; most of
      them had followed intrapericardial pneumonectomies for malignant pulmonary
      tumors. We present an uncommon event of heart herniation after a completion
      pneumonectomy indicated for chronic bronchiectasis. A 35-year-old male patient
      was operated for left completion pneumonectomy. A 6 cm x 4 cm area of adherent
      pericardium near the obtuse margin of heart was removed during surgery. During
      head-end elevation of the bed in postoperative intensive care unit, patient got
      accidentally tilted to the left side, which resulted in ventricular fibrillation.
      Chest cavity was re-opened for cardiopulmonary resuscitation. Left ventricle was
      found herniating through the pericardial deficiency into the left-thoracic cavity
      with the cardiac apex touching chest wall. During surgical re-exploration, the
      pericardial deficiency was closed with a synthetic Dacron patch. Hemodynamic
      condition remained stable in the immediate postoperative period. Patients had
      infection of the left thoracic cavity after 5 weeks, for which he was subjected
      to thoracoplasty and omentopexy. Prompt recognition with timely intervention is
      life saving from cardiac herniation. Strategy of closing the pericardial defect
      after pneumonectomy should be followed routinely, irrespective of the indication
      for pneumonectomy.

PMID- 20826969
TI  - Perioperative anesthetic management of patients with hypertrophic cardiomyopathy
      for noncardiac surgery: a case series.
AB  - Hypertrophic cardiomyopathy with or without left ventricular outflow tract
      obstruction is characterized by asymmetric hypertrophy of the interventricular
      septum causing intermittent obstruction of the left ventricular outflow tract.
      Because Hypertrophic cardiomyopathy is the most common genetic cardiovascular
      disease, it may present to the anesthesiologist more often than anticipated,
      sometimes in undiagnosed form during routine preoperative visit. Surgery and
      anesthesia often complicate the perioperative outcome if adequate monitoring and
      proper care are not taken. Therefore, a complete understanding of the
      pathophysiology, hemodynamic changes and anesthetic implications is needed for
      successful perioperative outcome. We hereby describe the perioperative management
      of three patients with Hypertrophic cardiomyopathy for different surgical
      procedures.

PMID- 20826970
TI  - Congenital hypopituitarism: monitoring after coronary artery bypass grafting.
AB  - Cardiovascular disease in patients with congenital hypopituitarism is not rare;
      however, there is a lack of reports referring to cardiac interventions in such
      patients. We present a 76-year-old man with complete pituitary hormone
      deficiency, who presented with recurrent events of unstable angina. He had a
      significant stenosis of the left anterior descending artery and he underwent off
      pump coronary artery bypass. Our aim is to present the successful management of
      this patient with congenital hypopituitarism who underwent cardiac surgery and to
      review the relevant literature.

PMID- 20826971
TI  - Interesting TEE image.

PMID- 20826972
TI  - An unusual case of thoracic gossypiboma.

PMID- 20826973
TI  - Anesthetic management of patent ductus arteriosus--not always an easy option.

PMID- 20826974
TI  - Post-operative management of endarterectomy.

PMID- 20826975
TI  - Kounis syndrome--the killer for Williams syndrome?

PMID- 20826976
TI  - Anesthesia for noncardiac surgery in infant with undiagnosed single ventricle.

PMID- 20826977
TI  - End to end anastomosis of an injured left anterior descending coronary artery.

PMID- 20826978
TI  - To evaluate the heart or not in emergency neurosurgical head-injured patients
      with ST elevation.

PMID- 20826979
TI  - Correlation between central venous-arterial carbon dioxide tension gradient and
      cardiac index changes following fluid therapy.

PMID- 20826980
TI  - Prevention of cardiac arrest due to anesthesia in Williams syndrome.

PMID- 20826981
TI  - Pediatric dermatoses in India.

PMID- 20826982
TI  - Undergraduate dermatology teaching in India: need for change.

PMID- 20826983
TI  - Mucocutaneous manifestations in children with human immunodeficiency virus
      infection.
AB  - Skin is one of the most frequently involved organs in human immunodeficiency
      virus (HIV) infection, and mucocutaneous manifestations may be one of the
      earliest markers of AIDS. The prevalence of cutaneous abnormalities in HIV
      approaches nearly 90%. Mucocutaneous manifestations may also act as a prognostic
      marker of HIV infection. Children are increasingly being affected by HIV
      infection and it is important to realize the presence of the infection early in
      the disease process as their immune status is not mature enough to handle the
      stress of various infections. Skin manifestations can serve as early markers and
      prognostic indicators of HIV infection. This review highlights the epidemiology,
      transmission, pathogenesis, and the mucocutaneous manifestations of HIV infection
      in children.

PMID- 20826984
TI  - Pediatric dermatology: part II.

PMID- 20826985
TI  - Infantile hemangioma: an update.
AB  - Infantile hemangiomas (IH) are neoplastic proliferations of endothelial cells,
      characterized by a period of growth after birth, and eventual spontaneous
      involution. The course can be uneventful, culminating in spontaneous resolution;
      or it may be marked by complications such as bleeding; ulceration; infection;
      visual, feeding and breathing compromise; cosmetic and life-threatening
      complications such as congestive heart failure. Recognition of associated
      syndromes and impending complications of hemangiomas is of utmost importance.
      Great advances have taken place in the nomenclature, pathogenesis,
      immunohistochemistry, diagnostic workup and management of hemangiomas in the
      recent years. This article reviews current advances in the understanding of the
      pathogenesis, diagnostic tools, medical and surgical modalities of treatment for
      infantile hemangiomas.

PMID- 20826986
TI  - Current concepts in the management of bacterial skin infections in children.
AB  - Bacterial skin infections in children vary widely clinically, starting from mild
      superficial folliculitis to deep necrotizing fasciitis. The causative organisms
      are mostly Staphylococcus aureus and Streptococcus, with occasional involvement
      of Gram-negative organisms. Treatment of even the milder forms of bacterial skin
      infections is of importance because of the long-term morbidity associated with
      them. However, because of global emergence of resistant strains of bacteria,
      treatment of these conditions is becoming increasingly difficult. The current
      antibacterial resistance patterns in organisms causing skin and soft tissue
      infections and the problems encountered in their management in children have been
      discussed.

PMID- 20826987
TI  - Sexually transmitted diseases in children in India.
AB  - Sexually transmitted diseases (STDs) in children are not uncommon in India,
      though systematic epidemiological studies to determine the exact prevalence are
      not available. STDs in children can be acquired via sexual route or, uncommonly,
      via non-sexual route such as accidental inoculation by a diseased individual.
      Neonatal infections are almost always acquired intrauterine or during delivery.
      Voluntary indulgence in sexual activity is also an important factor in
      acquisition of STDs in childhood. Sexual abuse and sex trafficking remain the
      important problems in India. Surveys indicate that nearly half of the children
      are sexually abused. Most at risk children are street-based, homeless or those
      living in or near brothels. Last two decades have shown an increase in the
      prevalence of STDs in children, though most of the data is from northern part of
      the country and from major hospitals. However, due to better availability of
      antenatal care to majority of women, cases of congenital syphilis have declined
      consistently over the past two-three decades. Other bacterial STDs are also on
      decline. On the other hand, viral STDs such as genital herpes and anogenital
      warts are increasing. This reflects trends of STDs in the adult population.
      Concomitant HIV infection is uncommon in children. Comprehensive sex education,
      stringent laws to prevent sex trafficking and child sexual abuse, and antenatal
      screening of all the women can reduce the prevalence of STDs in children.

PMID- 20826988
TI  - Cutaneous tuberculosis in children: the Indian perspective.
AB  - Cutaneous tuberculosis continues to be a significant medical problem even with
      the advent of highly effective antituberculous drugs. It constitutes about 1.5%
      of all extra pulmonary tuberculosis. The prevalence in children varies from 18 to
      54% in India. There is no gender predilection and the infection occurs with
      increased frequency in 10-14 year age group. Intrafamilial source of TB has been
      observed very frequently. A concomitant TB lymphadenitis is most common while
      involvement of other systemic organs like lung, bone and abdomen has also been
      observed. Protective efficacy of BCG is debatable and not yet fully defined. Of
      all the clinical types, scrofuloderma (SFD) is the most commonly encountered
      variant followed by lupus vulgaris (LV) and tuberculosis verrucosa cutis (TBVC).
      Lichen scrofulosorum (LS) is generally found to be associated with systemic TB
      focus in about 72% of cases. The impact of HIV on childhood cutaneous TB seems to
      be minimal. Similar to adults, the diagnosis of cutaneous tuberculosis relies
      mainly on histopathology, culture on LJ medium or radiometric BACTEC 460 TB
      culture system and PCR. In addition Mantoux positivity and a positive therapeutic
      trial with anti-tubercular drugs may be a good pointer to tubercular infection. A
      thorough clinical evaluation and exhaustive investigations to pin-point
      associated systemic focus is advocated as the latter has an impact on the
      duration of treatment. Cutaneous TB in children is treated as per the
      recommendations of therapy for extrapulmonary TB.

PMID- 20826989
TI  - Atopic dermatitis in infants and children in India.
AB  - Atopic dermatitis (AD) is a chronic relapsing eczematous skin disease
      characterized by pruritus and inflammation and accompanied by cutaneous
      physiological dysfunction, with a majority of the patients having a personal or
      family history of "atopic diathesis." The term "atopic diathesis" refers to the
      presence of allergic rhinitis, bronchial asthma or AD. The universal occurrence
      of AD is no longer debated. However, published material about its natural
      history, etiopathogenesis, epidemiology, clinical patterns and management leave a
      lot to be known in the Indian scenario. In the present write-up, we will try to
      explore the wealth of knowledge about the disease available in our country and
      try to unfurl the complex interplay of different factors that are implicated for
      the development of this condition. The diagnosis of AD is based on a
      constellation of signs and symptoms. There is no laboratory "gold standard" for
      the diagnosis of AD. In a majority of the cases, the diagnosis is quite easy.
      Topical corticosteroids form the mainstay of topical treatment and, along with
      emollient, are able to control the condition in more than 80% of the cases.
      However, as use of long-term topical corticosteroid has the potential to produce
      local and systemic adverse effects, topical tacrolimus has come up as a useful
      molecule for the long-term control of the disease.

PMID- 20826990
TI  - Pediatric contact dermatitis.
AB  - Allergic contact dermatitis (ACD) in children, until recently, was considered
      rare. ACD was considered as a disorder of the adult population and children were
      thought to be spared due to a lack of exposure to potential allergens and an
      immature immune system. Prevalence of ACD to even the most common allergens in
      children, like poison ivy and parthenium, is relatively rare as compared to
      adults. However, there is now growing evidence of contact sensitization of the
      pediatric population, and it begins right from early childhood, including 1-week
      old neonates. Vaccinations, piercing, topical medicaments and cosmetics in
      younger patients are potential exposures for sensitization. Nickel is the most
      common sensitizer in almost all studies pertaining to pediatric contact
      dermatitis. Other common allergens reported are cobalt, fragrance mix, rubber,
      lanolin, thiomersol, neomycin, gold, mercapto mix, balsum of Peru and colophony.
      Different factors like age, sex, atopy, social and cultural practices, habit of
      parents and caregivers and geographic changes affect the patterns of ACD and
      their variable clinical presentation. Patch testing should be considered not only
      in children with lesions of a morphology suggestive of ACD, but in any child with
      dermatitis that is difficult to control.

PMID- 20826991
TI  - Phototherapy and photochemotherapy in childhood dermatoses.
AB  - The concept of phototherapy and photochemotherapy is not new, and sophisticated
      ultraviolet (UV) treatment modalities are available for almost three decades.
      However, phototherapy has not been used in children as extensively as in adults,
      probably due to long-term safety concerns. Photochemotherapy (psoralen plus UVA)
      is not considered to be safe in the younger age group. UV therapies can be useful
      treatment options for children with selected dermatological conditions provided
      they are used under carefully controlled conditions. Presently there is
      insufficient data available to provide recommendations regarding the safe maximum
      dose and duration of phototherapy in children. Developments of new UV delivery
      systems and devices are aimed at improving the safety and efficacy of
      phototherapy. In this review, we discuss the published literature on phototherapy
      and photochemotherapy in children, drawbacks of their use in pediatric population
      and future prospects.

PMID- 20826992
TI  - Tinea capitis in the pediatric population: a study from North India.
AB  - BACKGROUND: Tinea capitis (TC) is a common superficial fungal infection seen
      predominantly in children. The etiological factors vary from one region to the
      other. The clinical and microbiological characteristics of the same were studied
      in patients up to the age of 12 years seen at a pediatric super specialty
      hospital in New Delhi, India. AIMS: To delineate the various patterns of TC
      observed in North India and to assess for any correlation between the clinical,
      microscopic and microbiologic findings in the patients seen. Also, to identify
      the common fungal species responsible for producing TC in North India. METHODS:
      Clinical morphology and KOH findings were studied in 214 patients with the
      suspected diagnosis of TC. Fungal culture were also performed for all the cases.
      An attempt was made to evaluate any correlation among the clinical, microscopic
      and etiological findings. The epidemiological factors associated with the disease
      were also assessed. RESULTS: TC was found to be most common in the 8-10-year age
      group, with noninflmmatory TC being the more common type (56.5%). A mixed
      morphological pattern was recorded in 10% of the cases. Microscopic examination
      revealed an endothrix pattern of hair invasion to be more common (41.5% cases).
      Again, 8.8% of the cases showed foci of both endothrix and ectothrix pattern of
      invasion simultaneously. Trichophyton violaceum was the most common fungal
      species isolated. CONCLUSIONS: In the present study, clinical morphology or KOH
      findings were not found to be clearly or exclusively predictive of the species
      involved. There was a fair degree of overlap in the clinical or microscopic
      patterns produced by the fungal species. Mixed patterns were observed both on
      clinical examination as well as on KOH examination. However, none of the
      specimens grew more than one fungal species.

PMID- 20826993
TI  - Comparative evaluation of NBUVB phototherapy and PUVA photochemotherapy in
      chronic plaque psoriasis.
AB  - BACKGROUND: Psoralen UV-A (PUVA) is an established therapy for psoriasis, but
      there is a well-documenated risk of melanoma and nonmelanoma skin cancer. Narrow
      band Ultraviolet-B (NBUVB) therapy has a lower carcinogenic risk, has equal
      therapeutic potential and is considerably safe in the long term than PUVA. AIM:
      The aim of present study was to compare the efficacy and side-effects of PUVA and
      NBUVB in chronic plaque psoriasis. METHODS: Sixty patients of chronic plaque
      psoriasis were taken up for the study and were randomly divided into two groups
      of 30 each. They were well matched in terms of age, sex, psoriasis extent and
      pretreatment psoriasis area severity index (PASI) scoring. One group was treated
      with twice-weekly narrow-band UV-B (TL-01) phototherapy and the other group
      received twice-weekly oral 8-Methoxsalen PUVA for a period of 3 months. RESULTS:
      Both the groups achieved >75% reduction in the PASI score or complete clearance
      at the end of 3 months, but PUVA group patients required significantly fewer
      number of treatment sessions and fewer number of days to clear the psoriasis as
      compared to the NBUVB group, while the mean cumulative clearance dose and adverse
      effects were significantly lower in the NBUVB group. CONCLUSION: We concluded
      that PUVA group patients achieved a faster clearance, but the adverse effects
      were significantly lower in the NBUVB group.

PMID- 20826994
TI  - Increased tissue leptin hormone level and mast cell count in skin tags: a
      possible role of adipoimmune in the growth of benign skin growths.
AB  - BACKGROUND: Skin tags (ST) are common tumors. They mainly consist of loose
      fibrous tissue and occur on the neck and major flexures as small, soft,
      pedunculated protrusions. Decrease in endocrine, hormone level and other factors
      are thought to play a role in the evolution of ST. Leptin is an adipocyte-derived
      hormone that acts as a major regulatory hormone for food intake and energy
      homeostasis. Leptin deficiency or resistance can result in profound obesity and
      diabetes in humans. A role of mast cell in the pathogenesis of ST is well
      recognized. AIMS: To investigate the role of leptin in the pathogenesis of ST and
      to clarify whether there is a correlation between mast cell count and leptin
      level in ST. METHODS: Forty-five skin biopsies were taken from 15 patients with
      ST. From each patient, a biopsy of a large ST (length >4 mm), a small ST (length
      <2 mm) and a normal skin biopsy (as a control) were taken. The samples were
      processed for leptin level. Skin biopsies were stained with hematoxylin and eosin
      and toluidine blue-uranyl nitrate metachromatic method for mast cell count was
      used. RESULTS: There was a significant increased level of leptin in the ST
      compared to the normal skin. It was highly significant in small ST than in big ST
      (P = 0.0001) and it was highly significant in small and big ST compared to
      controls, P = 0.0001 and P = 0.001, respectively. There was a significant
      increase in mast cell count in the ST, which did not correlate with the increased
      levels of leptin. CONCLUSION: This is the first report to demonstrate that tissue
      leptin may play a role in the pathogenesis of ST. The significant increase in the
      levels of leptin and mast cell count in ST may indicate a possible role of
      adipoimmune in the benign skin growths.

PMID- 20826995
TI  - Pilomatricoma: a tumor with hidden depths.
AB  - BACKGROUND: Pilomatricoma is a benign tumor of hair matrix differentiation and
      has been classically described as comprising of basaloid and shadow cells admixed
      with multinucleated giant cells and areas of calcification. However, there are a
      diverse range of histologic features this tumor displays that are often
      unrecognized. AIMS: This study was undertaken to record the histopathologic
      features of pilomatricoma with an emphasis on the occurrence of other forms of
      differentiation. METHODS: The study included all skin biopsy specimens over a 13
      year period from 1995 to 2007 that had a histologic diagnosis of pilomatricoma.
      Hematoxylin and eosin-stained slides were reviewed. RESULTS: This study included
      21 cases of pilomatricoma. Supramatrical differentiation was seen in all cases
      and three-quarters of the cases showed matrical differentiation. Also observed in
      some of the cases were clear cell differentiation toward the outer root sheath,
      infundibular differentiation, calcification, ossification and secondary
      inflammation with a foreign body giant cell reaction. Epidermal induction in the
      form of a downward plate-like growth of the epidermis was seen in a few cases.
      CONCLUSION: Pilomatricoma, although considered a tumor of hair matrix
      differentiation, can show cellular evolution toward the other parts of the hair
      follicle, such as the outer and inner root sheaths, sebaceous and infundibular
      components and, therefore, can be considered a panfollicular neoplasm.

PMID- 20826996
TI  - Pseudoepitheliomatous, keratotic, and micaceous balanitis presenting as cutaneous
      horn in an adult male.
AB  - Pseudoepitheliomatous, keratotic, and micaceous balanitis is an extremely rare
      condition occurring over the glans in elderly characterized by silvery white
      plaque with mica-like crust, which can undergo malignant transformation. Herein
      we present a case of pseudoepitheliomatous, keratotic, and micaceous balanitis
      occurring in an adult male presenting as a cutaneous horn.

PMID- 20826997
TI  - Waardenburg syndrome: a report of three cases.
AB  - Waardenburg syndrome (WS) is a rare autosomally inherited and genetically
      heterogeneous disorder of neural crest cell development with distinct cutaneous
      manifestations. Based on the clinical presentations, four subtypes of the disease
      are recognized. A careful clinical evaluation is required to differentiate
      various types of WS and other associated auditory-pigmentary syndromes. We
      describe a case series of WS to highlight the wide spectrum of manifestations of
      the syndrome including a rare association.

PMID- 20826998
TI  - Acroangiodermatitis of mali: a rare vascular phenomenon.
AB  - Acroangiodermatitis (synonym pseudo-Kaposi sarcoma) is an unusual, benign
      condition which clinically presents as purple-colored patches, plaques or
      nodules, mostly on the extensor surfaces of lower extremities in patients with
      chronic venous insufficiency and arteriovenous malformations. It resembles
      aggressive conditions like Kaposi's sarcoma and requires histopathological
      examination for its diagnosis. We report two such cases of acroangiodermatitis.
      Histopathology of both the cases showed dilated capillaries in the dermis with
      extravasated red blood corpuscles (RBCs), hemosiderin deposits, and hyperplastic
      granulation tissue. Both were treated with oral antibiotics and topical steroids.
      The ulcers showed a good response within 2 months of treatment.

PMID- 20826999
TI  - Autosomal dominant epidermodysplasia verruciformis: a clinicotherapeutic
      experience in two cases.
AB  - Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by a
      unique susceptibility to cutaneous infection by a group of phylogenetically
      related human papilloma viruses (HPVs). These patients show a defect in cell
      mediated immunity specific toward the causative HPVs that lead to lifelong
      disease. The defect is usually inherited as autosomal recessive trait and
      presents clinically with plane warts, pityriasis versicolor-like lesions and
      reddish verrucous plaques. Dysplastic and malignant changes in the form of
      actinic keratoses, Bowen's disease and squamous cell carcinoma (SCC) are common
      but metastasis occurs rarely. A totally effective treatment against EV is as yet
      highly desirable. Two siblings having autosomal dominant EV presented with
      multiple actinic keratoses in addition to classic lesions. One of them had also
      developed well-differentiated SCC over forehead with metastases to regional lymph
      nodes. They were treated with combination of excision of small
      malignant/premalignant lesions, topical 5-flurouracil and sun protection.
      Additionally, elective excision/grafting of large SCC was performed after
      chemotherapy/radiotherapy in patient with metastatic SCC. Oral acitretin (25
      mg/day) was of benefit in the other patient. Overall clinicotherapeutic
      experience in both the patients is discussed here.

PMID- 20827000
TI  - Pitfalls of the novel parameter, n-index.

PMID- 20827001
TI  - Linear epidermolytic acanthoma or adult-onset verrucous epidermal nevus?

PMID- 20827002
TI  - Mucocutaneous features of hand, foot, and mouth disease: a reappraisal from an
      outbreak in the city of Kolkata.

PMID- 20827003
TI  - Contact dermatitis in nurses and paramedicals in a tertiary care hospital of
      northern India.

PMID- 20827004
TI  - Granuloma annulare - histology reconsidered.

PMID- 20827005
TI  - Herpes zoster motor neuropathy: a clinical and electrophysiological study.

PMID- 20827006
TI  - Scarification practice and scar complications among the Nigerian Yorubas.

PMID- 20827007
TI  - Bacteriological profile of community-acquired pyodermas with special reference to
      methicillin resistant Staphylococcus aureus.

PMID- 20827008
TI  - Extrusion of pilosebaceous unit into blister cavity of pemphigus vulgaris: an
      artifact occurring as a natural phenomenon in pemphigus vulgaris.

PMID- 20827009
TI  - Cutaneous relapse of primary testicular non-Hodgkin lymphoma-the first sign of
      disease dissemination.

PMID- 20827010
TI  - Multiple elastomas in a 6-month-old child.

PMID- 20827012
TI  - Pharmaceutical industry and continuing medical education.

PMID- 20827011
TI  - Familial anterior cervical hypertrichosis.

PMID- 20827013
TI  - Moulages of J. J. Hospital.

PMID- 20827014
TI  - Finger like growth and multiple nodules over right upper back.

PMID- 20827015
TI  - Idiopathic eruptive macular pigmentation or acanthosis nigricans?
AB  - A 21-year-old male presented with numerous asymptomatic dark brown to brown black
      pigmented macules and barely raised plaques on the face, trunk and extremities,
      developing over a period of 2 year. The surface of most lesions had a velvety
      raised surface similar in appearance to acanthosis nigricans and a biopsy from
      one of the lesions showed pigmented papillomatosis. This case fulfils all the
      criteria for idiopathic eruptive macular pigmentation (IEMP) with papillomatosis,
      and the clinical appearance of acanthosis nigricans in most lesions suggests that
      IEMP is a form of eruptive acanthosis nigricans.

PMID- 20827016
TI  - Hutchinson-Gilford progeria syndrome.
AB  - Progeria is a rare genetic disorder characterized by premature aging, involving
      the skin, bones, heart, and blood vessels. We report a 4-year-old boy who
      presented with clinical manifestations of progeria. He had characteristic facies,
      prominent eyes, scalp and leg veins, senile look, loss of scalp hair, eyebrows
      and eyelashes, stunted growth, and sclerodermatous changes. The present case is
      reported due to its rarity.

PMID- 20827017
TI  - A study to evaluate the efficacy and safety of hydrocortisone aceponate 0.127%
      lipophilic cream in steroid responsive dermatoses in Indian patients.
AB  - BACKGROUND: Topical corticosteroids (CSs) are the mainstay of therapy in various
      steroid responsive dermatoses. Newer CSs are more efficacious and safer than the
      older ones. There is no published data on the efficacy and safety of a new
      steroid hydrocortisone aceponate in the Indian population. AIM: To evaluate the
      efficacy and safety of hydrocortisone aceponate (0.127%) lipophilic cream in the
      treatment of steroid responsive dermatoses in Indian patients. METHODS: Four
      hundred and fifteen patients with clinically diagnosed steroid responsive
      dermatoses enrolled in this study. They were advised to apply hydrocortisone
      aceponate (0.127%) lipophilic cream as a thin film to all the affected areas
      twice daily. Cleansing was done prior to the application with either soap-free
      cleanser or soap (that would not affect the study result). Use of oral
      antihistamines and/or antibiotics was permissible. However, other oral/topical
      steroid use was not permitted during the study. Patients were evaluated at day 0
      and at day 21. Data were recorded regarding clinical improvement and side
      effects, if any. They were then analyzed to determine the efficacy and safety of
      the cream. RESULTS: Physician's global evaluation of therapy showed that lesions
      were cleared in 82 (22.10%), excellent result in 200 (53.91%), good result in 72
      (19.41%), fair response in 15 (4.04%) and no change in 2 (0.54%) patients. There
      was no history of exacerbation in any patient. CONCLUSION: The study showed that
      hydrocortisone aceponate (0.127%) lipophilic cream is an effective therapeutic
      agent with a very good safety profile in various steroid responsive dermatoses in
      the Indian patient population.

PMID- 20827018
TI  - Angel's kiss in three generations.

PMID- 20827019
TI  - Quality of life in patients with vitiligo: a descriptive study on 83 patients
      attending a PUVA therapy unit in Imam Reza Hospital, Mashad.

PMID- 20827020
TI  - Generalized papular and sclerodermoid eruption: scleromyxedema.
AB  - Scleromyxedema (SM) is a rare chronic progressive and highly intractable
      cutaneous disease with unknown etiology, affecting both genders equally between
      30 and 50 years. The disease is characterized with mucin deposits in the skin
      and/or other organs. In fact it is a clinicopathological subset of lichen
      myxedematosus (LM) according to a new classification. Sclerodermiform plaques and
      lichenoid papules are characteristic cutaneous lesions. An elevation of IgG
      lambda (lambda) chain exists in most cases and extracutaneous involvement
      occurring with variable systemic findings is also detected. Generalized form is
      quite difficult to treat and may even be fatal. Herein, we present a male patient
      with typical features of generalized papular and sclerodermoid LM variety and
      with benign outcome by isotretinoin.

PMID- 20827021
TI  - Tense vesicles on the dorsum of tongue.

PMID- 20827022
TI  - Interdigital basal cell carcinoma of the hand: a rare site.

PMID- 20827025
TI  - Meta-analysis of randomized controlled trials on the treatment of pulmonary
      arterial hypertension.

PMID- 20827026
TI  - Waist-height ratio, indicator of central obesity, is strongly related to waist
      circumference but there is poor additional information regarding waist
      circumference.

PMID- 20827027
TI  - Fluffy luminal surface of the non-stenotic culprit coronary artery in patients
      with acute coronary syndrome: an angioscopic study.
AB  - BACKGROUND: Approximately 15% of acute coronary syndrome (ACS) cases have no
      significant coronary stenosis. Mechanisms underlying the attacks are, however,
      unknown. METHODS AND RESULTS: The clinical study had 254 patients with ACS; 38
      patients (31 females and 7 males; aged 51.0 +/- 8.0 years) had no significant
      coronary stenosis on angiography. They underwent a dye-staining angioscopy of the
      suspected culprit coronary artery using Evans blue, which selectively stains
      fibrin and damaged endothelial cells. A fluffy coronary luminal surface was
      observed in the suspected culprit artery in all 38 patients. The fluffy luminal
      surface was stained blue with Evans blue. In animal experiments involving 5
      beagles, 10% hydrogen peroxide solution was injected into the iliac arteries to
      damage endothelial cells, which was then followed by blood reperfusion, and then
      the artery was examined by intravascular microscopy and histology. In the
      beagles, the arterial segment, where the thrombus had been formed, exhibited a
      fluffy luminal surface after a washout of the thrombus, and the surface was
      stained blue. Histologically, the fluffy surfaces were composed of damaged
      endothelial cells attached by multiple fibrin threads and platelets. CONCLUSIONS:
      It was considered that the coronary segment exhibiting a fluffy luminal surface
      was the culprit lesion and that the fluffy surface was caused by residual thrombi
      after dispersion of an occlusive thrombus, which had formed on the damaged
      endothelial cells.

PMID- 20827028
TI  - Addition of losartan to angiotensin-converting enzyme inhibitors improves insulin
      resistance in patients with chronic heart failure treated without beta-blockers.
AB  - BACKGROUND: Angiotensin II and insulin resistance (IR) have clinical implications
      in the pathophysiology of chronic heart failure (CHF). However, it is still
      unclear whether the combination of an angiotensin-receptor blocker and
      angiotensin-converting enzyme inhibitor (ACEI) improves IR in CHF patients who do
      not receive beta-blockers. Thus, the aim of the present study was to evaluate the
      effects of losartan on glucose metabolism and inflammatory cytokines in CHF
      patients treated with ACEI but not beta-blockers. METHODS AND RESULTS: The effect
      of losartan treatment for 16 weeks on IR was analyzed in 16 CHF patients in a
      randomized crossover trial. Insulin level and homeostasis model IR index (HOMA
      IR) decreased significantly (P<0.05), but fasting plasma glucose did not change
      significantly. Serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and
      monocyte chemoattractant protein (MCP)-1 levels were significantly decreased with
      losartan (P<0.05). Furthermore, the changes in IL-6 and MCP-1 levels were
      significantly correlated with the reduction in HOMA-IR (P<0.05), but the change
      in TNF-alpha levels was not significantly correlated. CONCLUSIONS: The addition
      of losartan to ACEI therapy improved IR and decreased inflammatory cytokines in
      CHF patients who did not receive beta-blockers.

PMID- 20827029
TI  - Exercise stress test results in patients with bare metal stents or drug-eluting
      stents: pathophysiological and clinical implications.
AB  - BACKGROUND: Drug-eluting stents (DES) have reduced restenosis following
      percutaneous coronary intervention (PCI), but they seem to be associated with
      increased coronary endothelial dysfunction compared to bare metal stents (BMS).
      No data are available about the prognostic value of exercise stress test (EST) in
      PCI patients in the DES era. METHODS AND RESULTS: The 160 patients with coronary
      artery disease (CAD) who underwent PCI with either BMS (n=86) or DES (n=74) were
      studied. EST was performed 1 month after PCI. DES patients had a higher rate of
      positive EST compared to BMS patients (49% vs 32%; P=0.03). At a median follow-up
      of 18 months DES showed a lower rate of target vessel revascularization (TVR)
      (hazard ratio (HR) 0.37, P=0.07), but a higher rate of acute myocardial
      infarction (AMI) (HR 3.33, P=0.08). At multivariate Cox-regression time to 1 mm
      ST and low-workload ischemia were independent predictors of AMI (HR 0.96, P=0.03;
      and HR 6.24, P=0.009, respectively), as well as of TVR (HR 0.96, P=0.007; and HR
      6.43, P=0.001, respectively). CONCLUSIONS: DES implantation is associated with a
      higher rate of positive EST, compared to BMS, 1 month after PCI, likely due to a
      higher prevalence of endothelial dysfunction. EST seems to be helpful in
      predicting clinical outcome in patients with coronary stent implantation.

PMID- 20827030
TI  - Kinetic polymerization behavior of fluorinated monomers for dental use.
AB  - The kinetic polymerization behavior of 2,2,2-trifluoroethyl methacrylate (TFEMA),
      1,1,1,3,3,3-hexafluoroisopropyl methacrylate (HFIPMA), 2,2,2-trifluoroethyl
      acrylate (TFEA) and 1,1,1,3,3,3-hexafluoroisopropyl acrylate (HFIPA) was
      determined by isothermal differential scanning calorimetry (DSC) and high
      performance liquid chromatography (HPLC) in order to improve the properties of
      fluorinated powder-liquid adhesive resins. Conversion and heat of polymerization
      were calculated, and the solubility of the homopolymers in common solvents was
      examined. Comparison of their polymerization reactivity with that of MMA revealed
      that the overall rate of polymerization initiated by benzoyl peroxide (BPO)
      decreased in the order TFEA>MMA>TFEMA>HFIPA>HFIPMA. Based on the retention time
      of the monomer determined by HPLC, the hydrophobicity of the monomers was found
      to increase in the order MMA<TFEA<TFEMA<HFIPA<HFIPMA. The overall research
      results suggested that TFEA and HFIPA would be potentially promising candidates
      for the monomer liquid component of fluorinated powder-liquid adhesive resins.

PMID- 20827031
TI  - MPC polymer regulates fibrous tissue formation by modulating cell adhesion to the
      biomaterial surface.
AB  - The aim of this study was to analyze the effects of 2-methacryloyloxyethyl
      phosphorylcholine (MPC) polymer on fibrous tissue formation and cell adhesion
      plaque (CAP)-forming reactions. Silastic elastomer (SE) plates coated
      (experimental group) and uncoated (control group) with MPC polymer were prepared
      for in vivo and in vitro experiments. For the in vivo animal experiments, SE
      plates were implanted subcutaneously in the rat dorsal region. At 4, 8, and 12
      weeks, thicknesses of the fibrous tissue capsules in the experimental group were
      lower than in the control group. Likewise, the amount of collagen in the
      experimental group was lower than that of the control group. For the in vitro
      cell culture experiments, KMST-6 fibroblast cells in the experimental group
      demonstrated enhanced cell migration, accompanied with a weaker expression of
      vinculin and a larger amount of filopodia. Furthermore, weaker expressions of
      paxillin, talin, and ROCK1, but stronger expression of cofilin, were observed in
      the experimental group. Taken together, these results suggested that MPC polymer
      regulated fibrous tissue formation by modulating cell adhesion through changes in
      local CAPs and downstream signaling.

PMID- 20827032
TI  - Degradability of fluorapatite-leucite ceramics in naturally acidic agents.
AB  - This study was conducted to evaluate the titratable acidity and effect of
      naturally acidic agents on the surface microhardness, elemental composition, and
      surface morphology of fluorapatite-leucite ceramics. One hundred and ten ceramic
      disks (IPS d.SIGN), 12.0 mm in diameter and 2.0 mm in thickness, were fabricated.
      Before immersion, the baseline data of Vickers microhardness and elemental
      composition were recorded. Four groups were immersed in acidic agents (citrate
      buffer solution, green mango juice, and pineapple juice) and deionized water
      (control) at 37oC for 168 hours, whereas one group was immersed in 4% acetic acid
      at 80oC for 168 hours. After immersion, specimens were evaluated and data were
      analyzed using one-way repeated ANOVA and Tukey's test (alpha=0.05).
      Microhardness values significantly decreased after immersion (p<0.05). In terms
      of elemental composition, the weight percentages of silicon, potassium, aluminum,
      and sodium also decreased after immersion (p<0.05). Results of this study showed
      that fluorapatite-leucite ceramics were affected by long-term immersion in acidic
      agents.

PMID- 20827033
TI  - The effect of an increase in the rate of multiple births on low-birth-weight and
      preterm deliveries during 1975-2008.
AB  - BACKGROUND: Despite the rapid increase in the rate of multiple births due to the
      growth of reproductive medicine, there have been no epidemiologic studies of the
      secular trends in the impact of multiple births on the rates of low-birth-weight
      and preterm deliveries in Japan. METHODS: Japanese vital statistics for multiple
      live births were obtained from the Ministry of Health, Labour and Welfare and
      reanalyzed. With singletons as the reference group, an analysis was performed of
      secular trends in relative risk and population attributable risk percent of low
      birth-weight (<2500 grams), very-low-birth-weight (<1500 grams), and extremely
      low-birth-weight (<1000 grams) deliveries, using 1975-2008 vital statistics, and
      of preterm deliveries (ie, before 37, 32, and 28 weeks), using 1979-2008 vital
      statistics. RESULTS: The rate of multiple births doubled during the past 2
      decades, and about 2% of all neonates are now multiples. The population
      attributable risk percent tended to increase during the same period for all
      variables, and was approximately 20% in 2008. CONCLUSIONS: The public health
      impact of the rapid increase in multiple births remains high in Japan.

PMID- 20827034
TI  - Change in activities of daily living, functional capacity, and life satisfaction
      in Japanese patients with subacute myelo-optico-neuropathy.
AB  - BACKGROUND: There have been few reports on longitudinal change in activities of
      daily living (ADL), functional capacity, and life satisfaction in patients with
      subacute myelo-optico-neuropathy (SMON). METHODS: A total of 1309 SMON patients
      40 to 79 years of age underwent a medical examination conducted by the SMON
      Research Committee during the period from 1993 through 1995 (baseline) in Japan;
      666 (51%) were followed-up after 12 years and were thus eligible for analysis. We
      calculated scores for ADL, functional capacity, and life satisfaction at
      baseline, and at 3, 6, 9, and 12 years after baseline, using data from medical
      examinations conducted in 1993 through 2007. The Barthel Index, the Tokyo
      Metropolitan Institute of Gerontology Index of Competence, and the patient's
      response to the question "Are you satisfied with life?" were used to assess ADL,
      functional capacity, and life satisfaction, respectively. RESULTS: As compared
      with baseline, the mean scores for ADL, functional capacity, and life
      satisfaction were all significantly lower after 12 years in men and women, with
      the exception of life satisfaction in women. The change in scores for functional
      capacity from baseline to year 12 was significantly associated with change in
      life satisfaction; however, the changes in ADL and age at baseline were not.
      CONCLUSIONS: We observed decreases in ADL, functional capacity, and life
      satisfaction among SMON patients. Our results suggest that a decrease in life
      satisfaction can be prevented by maintaining or improving functional capacity.

PMID- 20827035
TI  - Relationship between the cumulative incidence of Kawasaki disease and the
      prevalence of electrocardiographic abnormalities in birth-year cohorts.
AB  - BACKGROUND: Kawasaki disease (KD) causes systemic vasculitis and coronary
      aneurysms. It frequently results in electrocardiographic (ECG) abnormalities of
      short duration. Cardiac sequelae persist beyond the acute stage in a few
      patients. There are many areas to be investigated concerning the effects on the
      vascular system of patients suffering from KD and its sequelae. METHODS: The
      cumulative incidences of KD and its cardiac sequelae were calculated in birth
      year cohorts, using data obtained from KD nationwide surveys. The results were
      compared with the prevalence of ECG abnormalities detected in cardiac
      examinations conducted at primary and secondary schools for each birth-year
      cohort. This comparison allowed observation of relationships in these trends for
      each birth-year cohort. RESULTS: The cumulative incidence of late-stage cardiac
      sequelae gradually declined. However, there were increases in the cumulative
      incidence of ECG abnormalities and in the cumulative incidences of KD and acute
      stage cardiac disorders related to KD. CONCLUSIONS: The results suggest that even
      among children without late cardiac sequelae, KD can have a persistent effect on
      the cardiovascular system. It thus appears necessary to extend clinical
      observation of children with a history of KD, even if they developed only acute
      stage cardiac lesions.

PMID- 20827036
TI  - A varying coefficient model to measure the effectiveness of mass media anti
      smoking campaigns in generating calls to a Quitline.
AB  - BACKGROUND: Anti-smoking advertisements are an effective population-based smoking
      reduction strategy. The Quitline telephone service provides a first point of
      contact for adults considering quitting. Because of data complexity, the
      relationship between anti-smoking advertising placement, intensity, and time
      trends in total call volume is poorly understood. In this study we use a recently
      developed semi-varying coefficient model to elucidate this relationship. METHODS:
      Semi-varying coefficient models comprise parametric and nonparametric components.
      The model is fitted to the daily number of calls to Quitline in Victoria,
      Australia to estimate a nonparametric long-term trend and parametric terms for
      day-of-the-week effects and to clarify the relationship with target audience
      rating points (TARPs) for the Quit and nicotine replacement advertising
      campaigns. RESULTS: The number of calls to Quitline increased with the TARP value
      of both the Quit and other smoking cessation advertisement; the TARP values
      associated with the Quit program were almost twice as effective. The varying
      coefficient term was statistically significant for peak periods with little or no
      advertising. CONCLUSIONS: Semi-varying coefficient models are useful for modeling
      public health data when there is little or no information on other factors
      related to the at-risk population. These models are well suited to modeling call
      volume to Quitline, because the varying coefficient allowed the underlying time
      trend to depend on fixed covariates that also vary with time, thereby explaining
      more of the variation in the call model.

PMID- 20827037
TI  - [Reactivation of hepatitis B and its prevention].

PMID- 20827038
TI  - [Current status and prevention of fulminant hepatitis due to hepatitis B
      reactivation].

PMID- 20827039
TI  - [Activation of hepatitis B virus after liver transplantation].

PMID- 20827040
TI  - [Preemptive therapy for HBV reactivation by serial HBV-DNA monitoring].

PMID- 20827041
TI  - [A case of lipoma of the lesser omentum with torsion of the pedicle in a twenty
      eight-year-old woman].
AB  - A 28-year-old woman was admitted to our hospital with abdominal pain. Abdominal
      CT scan demonstrated a well-demarcated heterogeneous lipid tumor about 8 cm in
      diameter anterior to the stomach. Abdominal ultrasonography (US) revealed a low
      echoic mass without enhancement of vascular images. We made a diagnosis of the
      lipoma, but not excluding the possibility of a liposarcoma, or the torsion of a
      tumor. We performed an operation to remove the tumor. Finally the tumor was
      diagnosed as a lipoma of the lesser omentum with torsion of the pedicle. This is
      the third reported case of torsion of a lipoma. In addition, this case is
      considered as the first such case of lipoma of the lesser omentum.

PMID- 20827042
TI  - [A case of gangliocytic paraganglioma with lymphoid metastasis].
AB  - We report a 67-year-old woman who had stiff shoulders and anemia. Upper
      gastrointestinal endoscopy revealed a pedunclated nodular submucosal tumor with
      erosions and surface ulcers in the second portion of the duodenum. These
      endoscopic findings were thought to be characteristic of gangliocytic
      paraganglioma. CT scan revealed suspected lymph node metastasis, thus the tumor
      was resected with pancreaticoduodenectomy and was found to be a gangliocytic
      paraganglioma associated with lymph nodal metastasis. Due to the rarity of the
      disease there is no consensus regarding treatment. Although this tumor is
      considered benign, the possibility exists for regional lymph nodal spread. The
      treatment should be well planned with continuous careful evaluation.

PMID- 20827044
TI  - [Accurate, preoperative diagnosis of duodenal duplication based on its
      characteristic endoscopic findings and radiographic presentation].
AB  - An 18-year-old woman was admitted to our hospital with pain in the right upper
      quadrant of the abdomen and fever. Diagnostic imaging studies, namely, upper
      gastrointestinal roentogenography and endoscopy, were performed, and an oval
      cystic tumor was detected in the second part of the duodenum. On the basis of the
      characteristic findings of the imaging studies and blood tests, we established a
      definitive diagnosis of duodenal duplication complicated with acute pancreatitis,
      even before surgical exploration. On surgical examination, the main pancreatic
      duct appeared to communicate internally with the cystic lesion. The
      histopathological examination of the surgical specimen confirmed the accuracy of
      the preoperative diagnosis.

PMID- 20827043
TI  - [Regression of MALT lymphoma of the rectum after Helicobacter pylori eradication
      therapy in a patient negative for Helicobacter pylori].
AB  - A 53-year-old woman was referred to our hospital for further examination of a
      rectal polypoid lesion. Colonoscopy revealed a submucosal tumor in the rectum
      (Ra) and a diagnosis of MALT lymphoma was made on the histological examination of
      the biopsy specimens and Southern blot analysis of the immunoglobulin heavy chain
      gene rearrangement. Although the patient was negative for Helicobacter pylori, H.
      pylori eradication therapy was performed. Colonoscopy 3 months after the
      eradication therapy showed disappearance of the rectal tumor. H. pylori
      eradication appears to be a useful treatment for not only H. pylori-positive
      colonic MALT lymphoma but H. pylori-negative colonic MALT lymphoma.

PMID- 20827045
TI  - [A bleeding ileal ulcer associated with Sweet's syndrome].
AB  - A 76-year-old woman was admitted to our institution because of high fever and
      erythema in the upper body with right back pain, and was given a diagnosis of
      Sweet's syndrome. She also had abdominal pain and developed hematochezia from the
      fourth hospitalization day. Double balloon enteroscopy detected multiple ulcers
      with a punched-out appearance at the terminal ileum. Endoscopic hemostasis of the
      ulcers was achieved using a hemoclip for treatment of a focal pulsating
      hemorrhage. After oral administration of prednisolone (PSL), both the ileal ulcer
      and erythema disappeared. The daily dosage of PSL was tapered. Since termination
      of PSL administration, there has been no recurrence of either Sweet's syndrome or
      ileal ulcer. We report a rare case of Sweet's syndrome complicated by bleeding
      ileal ulcers.

PMID- 20827046
TI  - [A case of hepatocellular carcinoma complicated with Caroli's disease].
AB  - A 29-year-old man was admitted with right hypochondralgia and fever. Markedly
      dilated bile ducts were observed, mainly in the right lobe of the liver. Based on
      both the clinical findings and imaging, we diagnosed Caroli's disease and
      choledochal cyst complicated with cholangitis. Hepatocellular carcinoma (HCC) was
      also observed in segment 3, and the tumor measured 4cm in diameter. The patient
      was successfully treated with hepatectomy of the right lobe, partial hepatectomy
      of the left lateral lobe, and bile duct reconstruction. A histopathological
      examination revealed moderately differentiated HCC without any components of
      cholangiocellular carcinoma (CCC). Although Caroli's disease is complicated with
      CCC, a case of Caroli's disease complicated with HCC, as in the present case, is
      quite rare and therefore is considered to be worthy of reporting.

PMID- 20827047
TI  - [Endoscopic ultrasound-guided transmural cyst drainage (EUS-CD) was effective in
      a case of pancreatic pseudocyst with obstructive jaundice and duodenal stenosis].
AB  - A 40-year-old man was admitted to our hospital because of epigastralgia and
      vomiting. His condition was diagnosed as acute pancreatitis with a pancreatic
      pseudocyst, obstructive jaundice, and duodenal stenosis. Because he had fever,
      abdominal pain, and elevated levels of C-reactive protein (CRP), endoscopic
      ultrasound-guided transmural cyst drainage (EUS-CD) was performed with a
      nasocystic tube on the 6th day. After the cyst was reduced and the patient
      recovered from the obstructive jaundice and duodenal stenosis, the nasal drainage
      tube was replaced with a plastic stent. Because a short extent of stenosis in the
      main pancreatic duct in the pancreatic head was found by endoscopic retrograde
      cholangiopancreatography (ERCP), a 5Fr pancreatic stent was placed to prevent
      pancreatitis. No recurrence of pancreatitis and the cyst occurred after removal
      of both stents 5 days later.

PMID- 20827048
TI  - [Retroperitoneal liposarcoma: a case report].
AB  - A 35-year-old woman who had visited an other hospital because of epigastralgia
      and anorexia was found to have a giant abdominal tumor, and was referred to our
      hospital. On admission, the abdomen was markedly distended. Abdominal CT scan and
      MRI showed the presence of a retroperitoneal tumor which occupied almost the
      entire abdominal cavity. She was operated a under a diagnosis of retroperitoneal
      liposarcoma. The tumor was located between the subphrenic space and the pelvic
      cavity, and was compressing the stomach, duodenum, pancreas and colon. Removal of
      the retroperitoneal tumor, including the right kidney, was performed. The
      resected tumor was 34 * 28 * 20 cm, weighed 5.5 kg and showed a variety of
      finding. The pathological diagnosis was a mixed type of retroperitoneal
      liposarcoma, consisting of well-differentiated type and myxoid type. We reported
      a case of giant retroperitoneal liposarcoma, with a review of the literature.

PMID- 20827049
TI  - [On "For eradication of stomach cancer in Japan", a special article by Prof.
      Masahiro Asaka].

PMID- 20827050
TI  - [Current knowledge on molecular features of seafood allergens].

PMID- 20827051
TI  - A major IgE epitope of rainbow trout collagen alpha2 chain.
AB  - Bovine collagen is allergenic and its major IgE epitope has already been
      identified. Fish collagen is also allergenic but shows no IgE cross-reactivity
      with bovine collagen, implying that it has specific IgE epitopes. Therefore, this
      study was initiated to elucidate IgE epitopes of rainbow trout collagen alpha2
      chain. Five overlapping proteins (R1-5; 221 or 225 amino acids long with an
      offset of 205 amino acids) covering the entire sequence of the rainbow trout
      collagen alpha2 chain were expressed in Escherichia coli. Immunoblotting
      experiments using 10 patients' sera reacting to fish collagen revealed that the
      major IgE epitope is included in the R5 protein (region 821-1,041). Then, 26
      overlapping peptides (20 or 21 amino acids long with an offset of 8 amino acids)
      encompassing the sequence of the R5 protein were chemically synthesized and
      examined for IgE-binding ability by fluorescence ELISA. Region 941-960 was found
      to be most IgE-reactive. When evaluated by inhibition ELISA, this region
      accounted for more than 50% of the IgE reactivity to the R5 protein. Moreover,
      the same region was found to be IgE-reactive in bastard halibut and zebrafish
      collagen alpha2 chains, but not in bovine collagen alpha2 chain. Our results
      strongly suggest that region 941-960 is a major common IgE epitope of fish
      collagen alpha2 chains.

PMID- 20827052
TI  - [Discrimination of plasticizers and screening of phthalates in polyvinyl chloride
      using DART-TOF/MS].
AB  - A technique using a direct analysis in real time (DART) ion source coupled with
      time of flight/mass spectrometry (TOF/MS) was developed to discriminate
      plasticizers and to screen phthalates in polyvinyl chloride (PVC). In DART-TOF/MS
      analysis of 40 plasticizers, the protonated molecular ion, [M+H](+), was detected
      for most plasticizers, and the molecular weight could be easily predicted. In the
      analysis of PVC sheets and toys, mass spectra of plasticizers were successfully
      detected, and accordingly, plasticizers in PVC were easily discriminated. PVC
      with a phthalates content in excess of 0.1% could be screened accurately
      according to the DART-TOF/MS ion intensity of phthalates corresponding to the
      limit of detection or a suitable criterion value. DART-TOF/MS analysis is a
      simple and rapid technique that is suitable for the discrimination of
      plasticizers and for screening of phthalates in PVC.

PMID- 20827053
TI  - [Toxicity and toxin profile of the dinoflagellate Alexandrium tamiyavanichii and
      toxic mussels in Harima-Nada of Seto Inland Sea, Japan].
AB  - From October to November 2004, the paralytic shellfish poison (PSP)-producing
      dinoflagellate Alexandrium tamiyavanichii was observed at Harima-Nada, Seto
      Inland Sea at a maximum cell density of 4,960 cells/L. The wild cells of the
      dinoflagellate collected from the same seawaters, and cultured cells derived from
      them showed toxicity scores of 6.25-15.4 x 10(-4) and 2.7-3.5 x 10(-4) MU/cell,
      respectively, both of which were much higher than those of previously reported
      strains. PSP of the wild cells was mainly composed of gonyautoxin (GTX) 5 (40.6
      52.4 mol%) and GTX4 (15.6-24.8 mol%), showing a unique composition that was
      greatly different from those of the previously reported strains, or of the
      cultured cells, whose main toxin component was GTX3 (average 37.6 mol%). The
      mussel Mytilus galloprovincialis collected from the same area in the same period
      accumulated a relatively high level of PSP (13-28 MU/g), suggesting a risk that
      A. tamiyavanichii may induce high-level PSP contamination of bivalves even at a
      cell density as low as around 5,000 cells/L.

PMID- 20827054
TI  - Determination method for total arsenic and partial-digestion method with nitric
      acid for inorganic arsenic speciation in several varieties of rice.
AB  - The determination method of total arsenic (As) and the speciation method of
      inorganic As for non-glutinous rice reported in our preceding paper were applied
      to several varieties of rice under optimized experimental conditions. In the
      determination of total As with ICP-MS, acetic acid was added to increase the
      sensitivity and an internal reference method with germanium was adopted to
      increase the precision. The extraction temperature in the partial-digestion
      method with nitric acid to speciate inorganic As was raised to 100 degrees C,
      because extraction efficiency over 90% was obtained from glutinous rice and
      colored rice at this temperature. In the investigation of polished and unpolished
      forms of non-glutinous, glutinous, and colored rice, the amounts of total and
      inorganic As were 0.04-0.54 mg/kg and 0.02-0.41 mg/kg, respectively. The color of
      rice was not related to total or inorganic As content. These results indicate
      that the inorganic As content in commercial rice should be carefully monitored.

PMID- 20827055
TI  - [Determination of residual pesticides in processed foods manufactured from
      livestock foods and seafoods using ion trap GC/MS].
AB  - A simultaneous method using iontrap gas chromatography/mass spectrometry (GC/MS)
      was developed for the determination of pesticide residues in four processed foods
      (frozen Chinese dumpling, eel kabayaki, corned beef and retort curry). Pesticide
      residues were extracted from samples with ethyl acetate-cyclohexane (1:1) in the
      presence of anhydrous sodium sulfate. The extract was concentrated and the
      residue was dissolved in n-hexane. The lipids in the extract were removed by
      acetonitrile-n-hexane partitioning, following which the acetonitrile layer was
      cleaned up using a C(18) mini-cartridge column and a graphite carbon/PSA silica
      (GCB/PSA) mini-cartridge column. The limits of quantification of compounds in 4
      processed foods were below 0.01 microg/g. The recoveries of 292 compounds spiked
      at 0.1 microg/g in 4 kinds of processed foods, and 210 to 262 pesticides showed
      acceptable recoveries of 70-120% with low repeatability (15%) and intermediate
      precision (<20%) only at the 0.1 microg/g spiked level. This method is expected
      to be useful for multi-residue analysis of pesticide residues in processed foods
      manufactured using livestock and seafoods as the main raw materials.

PMID- 20827057
TI  - Incorrect attribution of cerebrospinal fluid HIV-1 virological escape and
      lymphocytic meningitis to lopinavir/ritonavir monotherapy.

PMID- 20827058
TI  - High neonatal concentrations of raltegravir following transplacental transfer in
      HIV-1 positive pregnant women.

PMID- 20827059
TI  - Infectiousness of HIV-infected homosexual men in the era of highly active
      antiretroviral therapy.

PMID- 20827060
TI  - Infectiousness of HIV-infected men who have sex with men in the era of highly
      active antiretroviral therapy.

PMID- 20827061
TI  - Texas Woman's University College of Nursing. "Pioneering nursing's future: an
      adventure in excellence.".

PMID- 20827062
TI  - ICU nurses' experiences in providing terminal care.

PMID- 20827063
TI  - Factors that influence pediatric intensive care unit nurses to leave their jobs.
AB  - The purpose of this qualitative study was to discover why 10 nurses voluntarily
      left the pediatric intensive care unit (PICU) at 1 large pediatric hospital in
      the southwest. Critical theory provided the philosophical framework, whereas
      action research and Heideggerian hermeneutic phenomenology provided the
      methodological framework. Data analysis was conducted using the circular
      hermeneutic process described by Heidegger and explicated by Diekelmann. From the
      findings of this study, it was concluded that there is an inescapable and
      inevitable tension between the human factors and the PICU work environment.
      Nurses identified the constitutive pattern of unrelieved job stress as the major
      reason they left the PICU. The multidimensional and interactive environmental
      characteristics of nature of the job, insufficient resources, and negative
      perceptions of managers/team leaders contributed to the development of job
      stress. The results of this study revealed the evidence needed to begin to focus
      on interventions in the areas of nursing practice, education, and research
      required, reducing the likelihood of losing more PICU nurses.

PMID- 20827064
TI  - High-tech/high-touch team-centered care provides best outcomes for wound
      prevention in critically ill patients.
AB  - The management of problem wounds by critical care nurses is a particular
      challenge in that their primary responsibilities revolve around emergent care and
      resuscitation of patients. However, with the identification of pressure wound
      development as a "never event" by Centers for Medicare & Medicaid Services and
      the escalating costs to more than $5 billion annually for treating chronic wounds
      in the US population, wound management has become a clinical imperative. The
      essence of nursing as a healing, caring profession should drive our efforts at
      reducing and/or eliminating any untoward complication that threatens the very
      being of our patients. Problem wounds represent such a challenge. This article
      examines wound management from both the science and art of nursing care. The
      science comprises advanced wound therapies including hyperbaric oxygen therapy,
      recombinant DNA growth factor therapy, human skin equivalents, V.A.C. Therapy,
      advanced support surfaces, and state-of-the-art dressings. The art of wound
      management resides in the development of a comprehensive wound center with both
      outpatient and inpatient capabilities including a hospital-based wound team of
      nursing specialists. The challenge of healing problem wounds requires a
      multidisciplinary approach, a dedication to measurable outcomes, and a passion
      for holistic, patient-centered interventions.

PMID- 20827065
TI  - Transfusion in the critically ill: does it affect outcome?
AB  - Anemia and red blood cell (RBC) transfusions are common in critically ill and
      injured, trauma, and surgical patients. Tolerance of anemia is highly variable,
      depending on the presence of cardiovascular and other comorbid diseases that may
      diminish the hemodynamic response to a lower hemoglobin (Hb) level. The quest to
      define a minimum threshold Hb concentration at which patients achieve significant
      benefit to improve outcome has not yet been identified. Complications related to
      RBC transfusion are related to RBC storage and intrinsic properties of donor
      allogeneic RBCs, including bacterial contamination, transfusion-related acute
      lung injury, and transfusion-related immunomodulation. The best evidence related
      to transfusion-related outcome involves titrating transfusion requirements to
      parameters of severity of illness rather than arbitrarily defined Hb levels.

PMID- 20827066
TI  - Ventilator-associated pneumonia: the importance of oral care in intubated adults.
AB  - Ventilator-associated pneumonia (VAP) occurs within 24 hours of intubation and
      mechanical ventilation. Health care costs related to increased patient mortality,
      extended length of stay, and patient well-being make treatment of VAP a priority
      in all health care settings. The Institute for Healthcare Improvements has
      developed the Ventilator Bundle as a group of interventions linked to ventilator
      care with demonstrated outcome improvements; removal of subglottic secretions is
      one of these recommendations. Dental plaque and bacterial colonization of
      pathogens is directly related to microaspiration of bacteria into the lungs. A
      moist environment in the mouth maintains normal oropharyngeal bacteria,
      preventing overgrowth of pathogenic bacteria. Frequent oral care to include twice
      a-day brushing of the teeth found a 69% reduction in respiratory tract
      infections.

PMID- 20827067
TI  - Pressure ulcer prevention: utilizing unlicensed assistive personnel.
AB  - The purpose of this article is to provide education to the RN regarding pressure
      ulcer prevention and best practice interventions. This investigation focuses on
      the definition of a pressure ulcer, risk factors for pressure ulcers, and the
      benefits and importance of using unlicensed assistive personnel to help prevent
      pressure ulcers. A comprehensive literature review was completed using the Texas
      Woman's University Library, the Texas Christian University Library, and the World
      Wide Web. The search engine used was Google. The databases included were CINAHL,
      Academic Search Complete, Cochrane Library, MEDLINE, and ProQuest Nursing &
      Allied Health Source. The literature was current, defined as from the last 10
      years, and the primary language searched was English. Full-text articles from
      these databases were included as well as print publications from the university
      collections. The key search terms from the literature review included (a)
      pressure ulcer, (b) prevention, (c) unlicensed assistive personnel, (d) nursing
      assistant, (e) theory of nursing knowledge, (f) incidence, (g) prevalence, (h)
      Braden scale, (i) moisture, and (j) repositioning. Best practice guidelines were
      reviewed via the Joanna Briggs database, National Guideline Clearinghouse,
      Cochrane Library, the Centers for Medicare & Medicaid Services, and the National
      Institutes of Health. Literature was synthesized to define evidence-based
      practices that would justify the use of unlicensed assistive personnel for the
      prevention and care of pressure ulcers.

PMID- 20827068
TI  - The need for critical care nursing skills in an acuity-adaptable care delivery
      system.
AB  - With the relentless pursuit of patient care quality and patient safety, one has
      to explore every possible avenue to transform and redesign care delivery to
      remain solvent and meet the health care needs of patients in the future. Keeping
      patients undergoing renal transplantation in the same room from admission to
      discharge positively impacts clinical care outcomes on length of stay and cost.
      The success of this kind of care delivery lies on 1-week didactic structured
      training of the transplant nurses based on critical care concepts to manage
      fluctuations in patients' condition. With an added 3 months clinical rotation in
      the critical care areas, the competent transplant nurses were able to care for
      the patients undergoing renal transplantation in the acuity-adaptable medical
      surgical transplant floor with confidence. A hybrid nurse was created who
      possessed both critical care and medical-surgical skills. This can be a potential
      trend in the professional nurse model to address the health care challenges we
      face today in terms of nursing shortage, abbreviated plan of care, and facility
      operation efficiency. Thus, the need for critical care nursing skills is
      invaluable to the success of an acuity-adaptable care delivery system.

PMID- 20827069
TI  - Emerging issues for the postbariatric surgical patient.
AB  - Millions of individuals in the United States and around the world are overweight
      or obese. Bariatric surgery is now considered an evidenced-based choice for
      sustainable long-term weight loss and may reduce obesity-related comorbidities
      such as diabetes and obstructive sleep apnea. As bariatric surgical procedures
      increase, it can be expected that intensive care unit (ICU) admissions will
      increase as well. An emerging ICU population includes postbariatric patients
      either immediately after undergoing bariatric surgery or returning for subsequent
      surgical procedures. Massive weight loss following surgery leads to an excess of
      lax, overstretched skin, causing physical discomfort and psychosocial problems.
      It is important to understand the complex pathophysiological changes that occur
      in order to care for this growing population of patients. This review addresses
      the growing and evolving issues related to the complex nature of the
      postbariatric ICU patients.

PMID- 20827072
TI  - Invasive candidiasis in critically ill patients: does progressing knowledge
      improve clinical management and outcome?

PMID- 20827074
TI  - From risk assessment to risk management.

PMID- 20827073
TI  - Early antifungal intervention strategies in ICU patients.
AB  - PURPOSE OF REVIEW: Despite progress in the understanding of the pathophysiology
      of invasive candidiasis, and the development of new classes of well tolerated
      antifungals, invasive candidiasis remains a disease difficult to diagnose, and
      associated with significant morbidity and mortality. Early antifungal treatment
      may be useful in selected groups of patients who remain difficult to identify
      prospectively. The purpose of this review is to summarize the recent development
      of risk-identification strategies targeting early identification of ICU patients
      susceptible to benefit from preemptive or empirical antifungal treatment. RECENT
      FINDINGS: Combinations of different risk factors are useful in identifying high
      risk patients. Among the many risk factors predisposing to invasive candidiasis,
      colonization has been identified as one of the most important. In contrast to
      prospective surveillance of the dynamics of colonization (colonization index),
      integration of clinical colonization status in risk scores models significantly
      improve their accuracy in identifying patients at risk of invasive candidiasis.
      SUMMARY: To date, despite limited prospective validation, clinical models
      targeted at early identification of patients at risk to develop invasive
      candidiasis represent a major advance in the management of patients at risk of
      invasive candidiasis. Moreover, large clinical studies using such risk scores or
      predictive rules are underway.

PMID- 20827075
TI  - Current world literature.

PMID- 20827077
TI  - Current world literature. Atherosclerosis: cell biology and lipoproteins.

PMID- 20827078
TI  - Nutrition and metabolism.

PMID- 20827079
TI  - MicroRNA-33: nature's own RNAi controls cholesterol homeostasis.

PMID- 20827080
TI  - Meta-analysis and causality: what about evidence-based biochemistry?

PMID- 20827081
TI  - Tune into fatty acids for epigenetic programming news.

PMID- 20827082
TI  - Therapy and clinical trials.

PMID- 20827084
TI  - The scope of practice of auditory and vestibular medicine.

PMID- 20827085
TI  - Medical management of common peripheral vestibular diseases.
AB  - PURPOSE OF REVIEW: Review of office-based medical management options for common
      vestibular diseases. RECENT FINDINGS: Basic science studies have defined the
      ionic homeostasis of the inner ear stria vascularis as a central principle in the
      understanding of inner ear disorders. New molecular channels for water
      homeostasis have been identified in the inner ear structures. Office-based
      history, neurotological physical examination and judicial use of audiovestibular
      testing have increased our ability to manage vestibular patients more cost
      effectively. Clinical studies supported the use of gentamicin and steroids
      intratympanic perfusion of the inner ear to augment traditional treatments of
      common vestibular disorders. SUMMARY: The molecular biology and ionic transport
      between the stria vascularis and endolymph provided further understanding to the
      pathology and treatment of inner ear disorders. The history, physical examination
      and judicial use of laboratory tests are very critical and cost-effective in
      managing patients with vestibular diseases. Treatments such as inner ear
      perfusion with gentamicin and steroids have helped control and stabilize vertigo
      and hearing loss in Meniere's disease. Canalith repositioning treatments and home
      based vestibular rehabilitation have improved our abilities to effectively manage
      patients with benign paroxysmal positional vertigo, uncompensated peripheral
      vestibular loss and multisensory deficit and age-related balance disorders.

PMID- 20827086
TI  - Current Opinion in Otolaryngology & Head and Neck Surgery. Current world
      literature.

PMID- 20827087
TI  - ACSM clinician profile.

PMID- 20827088
TI  - Throw no stones: how to prevent calcium oxalate renal stones.

PMID- 20827089
TI  - Is generic physical activity or specific exercise associated with motor
      abilities?

PMID- 20827092
TI  - Hip injuries in young athletes.
AB  - The hip is an area of the body commonly injured in athletes and one that requires
      special consideration in the pediatric and adolescent athlete. This article
      reviews diagnoses specific to the young athlete and discusses more recent
      advances in imaging of the hip and arthroscopic treatment of the hip in the young
      athlete.

PMID- 20827090
TI  - Osteochondroses and apophyseal injuries of the foot in the young athlete.
AB  - With an increase in involvement in sports activities by children and adolescents,
      there has been a concomitant increase in both acute and overuse injuries. The
      pediatric skeleton lends itself to injuries unique to the young athlete,
      including various apophysites and osteochondroses. It is important for primary
      care and sports physicians treating the athlete to be aware of normal and
      abnormal variations in the pediatric skeleton, as well as common sites of injury
      in the pediatric foot. This article provides an overview of some of the most
      common skeletal foot injuries in the pediatric athlete, including Freiberg's
      infraction, Sever's disease, Kohler's disease, os navicularis, and Iselin's
      disease.

PMID- 20827093
TI  - Understanding the different physical examination tests for suspected meniscal
      tears.
AB  - Meniscal tears are common in sport medicine practice. Many articles and textbooks
      discuss the relative validity of the different components of the physical
      examination with respect to their sensitivity, specificity, and positive/negative
      predictive values as if they were diagnostic tests. In this article, we
      demonstrate why this approach is limited, including the heterogeneous nature of
      meniscal tear pathology (e.g., posterior vs anterior). Therefore, in this
      article, we categorize all the published tests in the literature with regards to
      the mechanism underlying a positive test. We believe our approach provides the
      clinician with additional tools to diagnose tears. Future research should explore
      predictive models based on the different components accounting for heterogeneous
      pathology and different patient contexts.

PMID- 20827094
TI  - A 17-year-old ballet dancer with medial ankle pain.

PMID- 20827095
TI  - Humeral shaft fracture in a baseball pitcher.

PMID- 20827096
TI  - Youth baseball injuries: recognition, treatment, and prevention.
AB  - Baseball is a very popular and safe sport for children and adolescents.
      Understanding bone maturation and risk factors for overuse will guide the
      practitioner to manage these athletes properly. Overuse injury risk can be
      minimized by limiting pitch counts, ensuring adequate recovery, developing proper
      mechanics, and allowing for early evaluation and intervention. Rest, albeit
      difficult for the athlete, is the mainstay of treatment for many of the maladies
      affecting this age group of throwers. Individualized approaches to treatment for
      this population are advised. Structural damage that may lead to surgery is rare
      but may need consideration if there is no response to conservative measures.
      Several resources are available to educate players, coaches, and parents
      regarding safe play.

PMID- 20827097
TI  - Equestrian sport-related injuries: a review of current literature.
AB  - Equestrian sports continue to grow in popularity in the Unites States and abroad,
      with an estimated 30 million people riding horses annually in the United States
      alone. Approximately one in five of these riders will suffer a serious injury
      during their riding career, requiring medical care and potentially
      hospitalization. Riding carries with it an implicit risk of injury associated
      with the unpredictability of the animals, the rider's head being positioned
      approximately 9 feet off the ground, and traveling unrestrained at speeds up to
      40 mph. This article reviews common equestrian injuries, epidemiology, mechanism
      of injury, risk factors, and prevention strategies, with an emphasis on the more
      dangerous aspects of the sport.

PMID- 20827098
TI  - Medical coverage of winter Nordic sports: an overview from the field.
AB  - Traveling with sports teams requires flexibility and a wide range of knowledge,
      as well as problem-solving abilities. Dominating the medical types of problems in
      the Nordic sports are the respiratory illnesses, especially asthma and upper
      respiratory infections (URI). Additionally, the team physician must have an
      awareness of antidoping issues. This overview highlights many of the issues
      encountered traveling domestically as well as internationally with high-level
      Nordic teams. Helpful links are included to facilitate the care of all levels of
      athletes. Additionally, a few side issues such as altitude illness and minor
      trauma are mentioned.

PMID- 20827099
TI  - An overview of strength training injuries: acute and chronic.
AB  - This article introduces the history of strength training, explains the many
      different styles of strength training, and discusses common injuries specific to
      each style. Strength training is broken down into five disciplines: basic
      strength or resistance training, bodybuilding, power lifting, style-dependant
      strength sports (e.g., strongman competitions, Highland games, field events such
      as shot put, discus, hammer throw, and javelin), and Olympic-style weightlifting.
      Each style has its own principal injuries, both acute and chronic, related to the
      individual technique. Acute injuries should be further categorized as emergent or
      nonemergent. Specific age-related populations (i.e., the very young and the aging
      athlete) carry additional considerations.

PMID- 20827100
TI  - American College of Sports Medicine Roundtable on exertional heat stroke--return
      to duty/return to play: conference proceedings.
AB  - On October 22-23, 2008, an ACSM Roundtable was convened at the Uniformed Services
      University (Bethesda, MD) to discuss return-to-play or return-to-duty for people
      who have experienced exertional heat illness (EHI) and to develop consensus-based
      recommendations. The conference assembled experts from the civilian sports
      medicine community and the Department of Defense to discuss relevant EHI issues,
      such as potential long-term consequences, the concept of thermotolerance, and the
      role of thermal tolerance testing in return-to-play decisions. Although the group
      was unable to move forward with new consensus recommendations, they clearly
      documented critical clinical concerns and scientific questions, including the
      following: 1) no uniform core definitions of EHI; 2) limited validated criteria
      to assess recovery from exertional heat stroke (EHS); and 3) inadequate ability
      to predict who may be predisposed to a subsequent heat injury after EHS. Areas of
      potential future research are identified.

PMID- 20827101
TI  - Autonomic dysfunction in noncirrhotic portal hypertension: its influence on
      variceal bleed.

PMID- 20827102
TI  - Cyclooxygenase-2 is overexpressed in aberrant crypt foci of smokers.

PMID- 20827103
TI  - Increased risk of concurrent asthma among patients with gastroesophageal reflux
      disease: a nationwide population-based study.
AB  - AIMS: The possibility of a relationship between gastroesophageal reflux disease
      (GERD) and asthma has been controversial. Using a nationwide population-based
      data set, this study aims to investigate the prevalence and risk of concurrent
      asthma among GERD patients, compared with patients without GERD in Taiwan.
      METHODS: This study used the National Health Insurance Research Database. A total
      of 61 941 patients with GERD and 61 941 randomly selected patients without GERD
      were included from the year 2006. Conditional logistic regression analyses were
      used to explore the risk of concurrent asthma for patients with and without GERD.
      Furthermore, the analyses performed were stratified by sex and age (18-44, 45-64,
      65-74 and > 74 years) to evaluate the association between GERD and concurrent
      asthma. RESULTS: Of the 123 882 sampled patients, 3% (3681 patients) were
      diagnosed with asthma in 2006, consisting of 3.9% of the GERD patients (2427 from
      the study group) and 2% of the patients without GERD (1254 from the comparison
      group). Conditional logistic regression analysis showed that the odds of
      concurrent asthma for patients with GERD were 1.97 times greater [95% confidence
      interval (CI) =1.84-2.12, P < 0.001] than the odds of asthma for patients without
      GERD. When stratifying by age groups, the odds ratios for GERD with concurrent
      asthma were 2.61 (95% CI=2.24-3.03, P<0.001) for patients 18-44 years of age,
      2.00 for patients 45-64 years of age (95% CI=1.79-2.23, P<0.001), 1.58 for those
      aged 65-74 (95% CI=1.36-1.83, P<0.001) and 1.80 for those aged 75 years or more
      (95% CI=1.52-2.12, P<0.001). CONCLUSION: Patients with GERD had a significantly
      higher risk of concurrent asthma compared with patients without GERD.